PMID- 11284221
TI  - Effect of long-term storage at -20 degrees C and -80 degrees C on apolipoprotein
      A1 and B in obese subjects.

PMID- 11284222
TI  - Measuring the effect of different agents on the viscosity of biological fluids: a
      novel method.

PMID- 11284223
TI  - Platelet and endothelial-cell markers in meningococcal septicaemia: a report of
      two cases.

PMID- 11284224
TI  - Serum cytokine levels in psoriasis vulgaris.

PMID- 11284225
TI  - Modulation of Porphyromonas gingivalis induced murine immune response in vitro by
      exogenous interleukin-12.

PMID- 11284226
TI  - Pseudohyperkalaemia and pseudomacrocytosis caused by inherited red-cell disorders
      of the 'hereditary stomatocytosis' group.
AB  - Unusual dominantly inherited conditions of the red cell, collected under the
      generic title 'hereditary stomatocytosis and allied disorders', exist, in which
      the red cell 'leaks' the univalent cations sodium (Na+) and potassium (K+). In
      some kindreds with these disorders, bizarre temperature effects can occur that
      have profound effects on the way in which the cells behave when removed from the
      body and cooled to either room or refrigerator temperatures. In some types, the
      cells lose K+ at room temperature, giving rise to pseudohyperkalaemia; in others,
      this occurs in concert with swelling of the red cell and pseudomacrocytosis. In
      some of these conditions, a red-cell abnormality is clearly demonstrated by the
      presence of haemolytic anaemia; however, routine haematology can be virtually
      normal in the milder versions. All are inherited as dominants, although new
      mutations can be seen.

PMID- 11284227
TI  - Acid-fast bodies in faecal smears stained by the modified Ziehl-Neelsen
      technique.
AB  - The modified Ziehl-Neelsen (ZN) stain has proved useful in the laboratory
      diagnosis of cryptosporidiosis and, more recently, for the laboratory diagnosis
      of cyclospora. Apart from cryptosporidia and cyclospora, many other organisms and
      artefacts are present in faeces, and may be seen in faecal smears stained by the
      modified ZN method. Described here is the presence of such organisms and
      artefacts in faecal samples submitted to the routine microbiology laboratory of a
      district general hospital. Over 6000 faecal smears were examined using the
      modified ZN method, with an incidence of cyclospora and cryptosporidium of
      approximately 0.1% and 1%, respectively. Other organisms and artefacts were
      observed, with an incidence ranging from 0.1% to 1%. It is emphasised that the
      identification of known gastrointestinal tract pathogens should not rely solely
      on the results of their staining reactions. It is essential that criteria such as
      morphology and size be taken into account to differentiate organisms with similar
      staining reactions.

PMID- 11284228
TI  - The visual theology of Victorian popularizers of science. From reverent eye to
      chemical retina.
AB  - This essay examines the use of visual images during the latter half of the
      nineteenth century in the work of three important popularizers of science. J. G.
      Wood, Richard Proctor, and Agnes Clerke skillfully used illustrations and
      photographs to establish their credibility as trustworthy guides to scientific,
      moral, and religious truths. All three worked within the natural theology
      tradition, despite the powerful critique of William Paley's argument from design
      set forth in Charles Darwin's Origin of Species (1859). Wood, Proctor, and Clerke
      recognized that in order to reach a popular audience with their message of divine
      wonder in nature, they would have to take advantage of the developing mass visual
      culture embodied in the new pictorial magazines, spectacles, and entertaining
      toys based on scientific gadgets emblematic of the reorganization of vision. But
      in drawing on different facets of the emerging visual culture and in looking to
      the images produced by the new visual technologies to find the hand of God in
      nature, these popularizers subtly transformed the natural theology tradition.

PMID- 11284229
TI  - Local knowledge, environmental politics, and the founding of ecology in the
      United States. Stephen Forbes and "The Lake as a Microcosm" (1887).
AB  - Stephen Forbes's "The Lake as a Microcosm" is one of the founding documents of
      the science of ecology in the United States. By tracing the connections between
      scientists and local fishermen underlying the research on floodplain lakes
      presented in "The Lake as a Microcosm," this essay shows how the birth of ecology
      was tied to local knowledge and the local politics of environmental
      transformation. Forbes and the other scientists of the Illinois Natural History
      Survey relied on fishermen for manual labor, expertise in catching fish, and
      knowledge of the natural history of the fishes. As Forbes and his colleagues
      worked in close contact with fishermen, they also adopted many of their political
      concerns over the privatization of the floodplain and became politically active
      in supporting their interests. The close connection between scientists and local
      knowledge forced the ecologists to reframe the boundaries of ecology as objective
      or political, pure or applied, local or scientific.

PMID- 11284230
TI  - Severo Ochoa and the biomedical sciences in Spain under Franco, 1959-1975.
AB  - The influence of Severo Ochoa in the establishment of biochemistry and molecular
      biology in Spain is the central topic of this essay. From the time he was awarded
      the Nobel Prize in Physiology or Medicine in 1959, Ochoa's links with Spanish
      scientists and top authorities in education and science became instrumental to
      the development of these areas in the country of his birth. Ochoa's influence is
      analyzed through investigation of three "events": the reception of the award in
      Spain and some of its immediate consequences; his role in the VIth Meeting of the
      Federation of European Biochemical Societies, held in Madrid in 1969; and the
      international scientific symposium, held in Madrid and Barcelona, that celebrated
      his seventieth birthday in 1975. After an account of Ochoa's biography up to
      1959, analysis of these events shows that Ochoa's influence cannot be understood
      without taking into account the political and scientific context of its
      reception.

PMID- 11284231
TI  - The "Revolution in chemistry and physics." Overthrow of a reigning paradigm or
      competition between contemporary research programs?
AB  - Recent revisionist interpretations of the chemical revolution have left intact
      the core of the traditional view that its central feature was the overthow of the
      phlogiston theory by the oxygen theory of combustion of Antoine Lavoisier. The
      central confrontation has been seen as that between the adherents of the chemical
      system that Lavoisier built around his theory and the form of the phlogiston
      theory defended by Joseph Priestley. This essay contends that Priestley's use of
      phlogiston was so loosely connected with the older phlogiston theories descended
      from that of Georg Ernst Stahl that the events at the heart of the chemical
      revolution should be viewed more as a competition between two rival new research
      programs than as the replacement of a reigning paradigm.

PMID- 11284233
TI  - Health tips. Keeping your teeth.

PMID- 11284232
TI  - Enlarged prostate gland. Many treatment options.

PMID- 11284234
TI  - Wearing hip protectors may prevent hip fractures.

PMID- 11284235
TI  - Multivitamins. Do you need one?

PMID- 11284236
TI  - Adrenal tumors. A cause for concern?

PMID- 11284237
TI  - Obsessive-compulsive disorder. No need to hide.

PMID- 11284238
TI  - My depression and anxiety symptoms have improved with medication, but now I'm
      having some sexual difficulties because of the drugs. Is there anything I can do?

PMID- 11284239
TI  - I'd like to start a walking program to get more exercise. Is there a right way to
      start?

PMID- 11284240
TI  - Finger clubbing in children with human immunodeficiency virus infection.
AB  - We investigated the frequency of finger clubbing in 150 HIV-infected children
      consecutively hospitalized for acute pneumonia in South Africa and described
      associated clinical, laboratory and radiological features. Clubbing occurred in
      30 of 150 (20%) HIV-infected children compared with one of 99 (1%) HIV-negative
      control patients, p < 0.001. Clubbing was associated with lower presenting heart
      and respiratory rates and enlarged parotid glands. Total and CD4 + lymphocytes,
      CD4:CD8 ratio and LDH were lower in children with clubbing, but serum protein and
      gammaglobulin were higher. No differences in the prevalence or type of microbial
      pathogens were found between the two groups. Clubbing was associated with a
      radiological diagnosis of LIP. Children with clubbing had a lower in-hospital
      mortality rate than those without clubbing (6.7% vs 24.2%, p = 0.035). In
      geographical areas with high HIV seroprevalence rates, the presence of clubbing
      in a child hospitalized for respiratory disease should raise the suspicion of HIV
      infection.

PMID- 11284241
TI  - Neonatal sepsis and mortality in a regional hospital in Trinidad: aetiology and
      risk factors.
AB  - A total of 132 neonatal deaths among 627 infants admitted to the neonatal ward of
      the San Fernando General Hospital, Trinidad over a 2-year period were reviewed.
      The most common cause of death was prematurity (43.9%). Infection was the second
      most common cause (21.2%). Pseudomonas aeruginosa and Staphylococcus aureus were
      the most frequently isolated organisms (43%). The major drugs used empirically in
      suspected cases of sepsis were ampicillin or ceftazidime plus gentamicin. About
      85% of S. aureus were resistant to ampicillin, and P. aeruginosa resistance to
      ceftazidime and gentamicin was 76.7% and 72.1%, respectively. Significant risk
      factors in maternal history were infrequent antenatal care and prolonged rupture
      of membranes. The incidence of infection among low birthweight infants was 85.6%.
      Early-onset sepsis (86.4%) seemed to have a nosocomial origin because of the type
      of pathogens seen. There is an urgent need to improve the staff-to-patient ratio
      in the neonatal unit and for staff to be constantly reminded to employ simple
      infection control practices such as proper hand-washing to reduce cross
      infections.

PMID- 11284242
TI  - Neonatal intestinal perforation in a developing country.
AB  - Between 1990 and 1999, 14 neonates with intestinal perforation were treated at
      the Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Median age at
      presentation was 9 days and median weight 2.65 kg. Five had high anorectal
      malformation, three Hirschsprung's disease and two ruptured exomphalos with bowel
      strangulation. Gastroschisis, strangulated inguinal hernia, ileal atresia and
      umbilical sepsis with evisceration accounted for one case each. Two of the
      perforations were iatrogenic during colostomy construction. Seven perforations
      were in the small bowel and seven in the colorectum. Three neonates had oedema
      and tenderness of the anterior abdominal wall, and pneumoperitoneum was seen in
      abdominal radiographs in two. All the infants had laparotomy, four under local
      anaesthesia, after resuscitation. Three had simple suture of the perforation,
      five had resection with primary anastomosis and six had exteriorization
      colostomy. Overall, eight (59%) died, five with colorectal perforation and three
      with small bowel perforation.

PMID- 11284243
TI  - Impact of education and training on neonatal resuscitation practices in 14
      teaching hospitals in India.
AB  - The impact of a neonatal resuscitation programme (NRP) on the incidence,
      management and outcome of birth asphyxia was evaluated in 14 teaching hospitals
      in India. Two faculty members from each institution attended a neonatal
      resuscitation certification course and afterwards trained staff in their
      respective hospitals. Each institution provided 3 months pre-intervention and 12
      months post-intervention data. Introduction of the NRP significantly increased
      awareness and documentation of birth asphyxia, as judged by an increased
      incidence of asphyxia based on apnoea or gasping at 1 and 5 minutes (p < 0.001
      and < 0.01, respectively). A significant shift towards more rational
      resuscitation practices was indicated by a decline in the use of chest
      compression and medication (p < 0.001 for each), and an increase in the use of
      bag and mask ventilation (p < 0.001). Although overall neonatal mortality did not
      decrease, asphyxia-related deaths declined significantly (p < 0.01).

PMID- 11284244
TI  - Sporadic neonatal schizencephaly associated with brain calcification.
AB  - Schizencephaly rarely presents in the neonatal period. We present the case of a
      baby girl born with growth retardation and microcephaly who developed seizures on
      the 3rd day of life. There was no clinical or laboratory evidence of a congenital
      viral infection but brain imaging revealed widespread calcification and bilateral
      schizencephaly clefts. By the age of 11 months, she had developed gross
      psychomotor retardation.

PMID- 11284245
TI  - Diet, clothing, sunshine exposure and micronutrient status of Arab infants and
      young children.
AB  - Vitamin C and D levels in Arab women and their newborn infants have been shown to
      be low. We investigated the prevalence of and risk factors for possible
      hypovitaminosis C and D in a convenience sample of 51 hospitalized children
      without clinical features of vitamin C or D deficiency. The mean age was 15.4
      months. The serum vitamin C concentration was low in the mothers but normal in
      the children. Both mothers and children had low serum 25-hydroxyvitamin D (25
      OHD) concentrations. Fifty per cent of the mothers and 22% of the infants and
      children had hypovitaminosis D (serum 25-OHD level < 25 nmol/l). Infants who
      received dietary vitamin D supplementation had a higher mean (SD) serum 25-OHD
      concentration than the unsupplemented group (62.5 (29.8) vs 38.5 (27.3), p =
      001). Cutaneous light exposure in these children was poor. The children's serum
      25-OHD concentration correlated with dietary vitamin D supplementation and
      maternal serum 25-OHD levels. The results suggest normal vitamin C status but a
      possible high prevalence of hypovitaminosis D in Arab children and their mothers
      in UAE. Health education to encourage greater sunshine exposure and improvement
      in maternal vitamin D stores and the availability of adequate vitamin D
      supplements would improve children's vitamin D status. The study indicates that
      hypovitaminosis D continues to be an important maternal and child health problem,
      despite the abundant sunshine.

PMID- 11284246
TI  - High prevalence of microcytic anaemia in Omani children: a prospective study.
AB  - Iron deficiency is a common cause of microcytic anaemia. However, a high
      prevalence of haemoglobinopathies in the Arab population makes differential
      diagnosis difficult. This prospective study of anaemia in children attending a
      regional hospital in the Sultanate of Oman looked at the prevalence and causes of
      anaemia in 256 children, 153 in the age group 3-5 years (group A) and 103 in the
      age group 10-12 years (group B). Of the children studied, 45.1% in group A and
      37.9% in group B were anaemic according to WHO criteria. All the anaemic children
      had low mean corpuscular haemoglobin and 75% showed microcytosis. Serum ferritin
      levels were normal and glucose-6-phosphate dehydrogenase deficiency did not
      contribute to the anaemia. The microcytosis and microcytic anaemia in the study
      population could be attributed to the alpha-thalassaemia trait which is highly
      prevalent in Oman. The information is of value in any country where there is a
      significant prevalence of alpha-thalassaemia genes because these can confound the
      diagnosis of iron deficiency.

PMID- 11284247
TI  - Diagnosis of pulmonary tuberculosis in children in an HIV-endemic area, Malawi.
AB  - The diagnosis of pulmonary tuberculosis (PTB) in young children is particularly
      complex in resource-poor regions where HIV infection is common. This study
      examines the impact of HIV infection on diagnosis in children with suspected PTB
      attending Queen Elizabeth Central Hospital, Blantyre. A total of 110 children (4
      months-14 years) were studied over a 4-month period. Clinical data were recorded
      and investigations included Mantoux test, chest X-ray, HIV status (HIV-PCR when
      younger than 18 months) and sputum, if available. Laryngeal swabs were compared
      with sputa or gastric aspirates in a subgroup of 60 children. All children were
      commenced on anti-TB therapy and followed for treatment response. Aware of the
      clinical overlap between HIV and TB infection, we used more limited criteria than
      recommended to allocate a final diagnosis following review of all data except HIV
      status. Final diagnosis included confirmed PTB (n = 8), probable PTB (n = 41),
      lymphocytic interstitial pneumonitis (n = 10), pulmonary Kaposi sarcoma (n = 3)
      and bronchiectasis (n = 5). Culture rates of M. tuberculosis were: five (27.8%)
      of 18 sputa, three (7.1%) of 42 gastric aspirates and four (6.6%) of 60 laryngeal
      swabs. The HIV infection rate was 70.6% overall and 57.8% in 45 children with
      confirmed or probable PTB. Although a positive contact history was more common in
      HIV-infected children, a final diagnosis of confirmed or probable PTB was less
      common than in HIV-uninfected children (36% vs 63%; p = 0.02). The Mantoux test
      was positive in 14 (19%) of 72 HIV-infected compared with 15 (50%) of 30 HIV
      uninfected children (p < 0.01). A final diagnosis could not be made in 43 (39%)
      of the study children with suspected PTB, the majority of whom were HIV-infected.
      HIV-infected children had a significantly poorer response to TB treatment and
      higher lost-to-follow-up rates.

PMID- 11284248
TI  - A health and nutritional profile of rural school children in KwaZulu-Natal, South
      Africa.
AB  - A community-based cross-sectional study was undertaken to measure anthropometric
      indices, micronutrient status and prevalence of parasite infections in 579 rural
      South African primary school children. Eleven schools were selected randomly from
      a Magisterial District in southern KwaZulu-Natal (KZN). In each school, all
      pupils aged between 8 and 10 years were selected. The following outcome measures
      were obtained: anthropometric--height for age, weight for age and body mass
      index; micronutrient status--anaemia, serum ferritin and vitamin A; and
      prevalence of parasite infections--Ascaris lumbricoides, Trichuris trichiura and
      Schistosoma haematobium. The observed prevalences were: stunting 7.3%,
      underweight for age 0.7%, and obesity 3.1%; anaemia 16.5% (Hb < 12 g/dl), vitamin
      A deficiency 34.7% (serum retinol < 20 micrograms/dl) and 28.1% with reduced
      serum ferritin (< 12 ng/ml); Trichuris trichiura 53.9%, Ascaris lumbricoides
      27.3% and Schistosoma haematobium 24.5%. We conclude that micronutrient
      deficiency, parasitic infestations and stunting remain significant problems among
      school-aged children in South Africa. Micronutrient supplementation and de
      worming provide opportunities for school-based health promotion and primary
      health care interventions, and might produce significant health and educational
      benefits.

PMID- 11284249
TI  - Detection of adenovirus infection in children in Jordan.
AB  - Between November 1997 and May 1998, 350 nasopharyngeal aspirates (NPA) were
      obtained from children admitted to the Respiratory Disease Unit at Princess Rahma
      Hospital, northern Jordan who were clinically diagnosed as suffering from
      respiratory tract infections. NPA were investigated for the presence of
      adenovirus using shell vial (SV) culture assay, conventional culture (CC) assay,
      and direct immunofluorescence assay (DFA). Of the 350 NPA, adenoviruses were
      detected in 54 (15.4%) by the combined techniques used. SV identified 34 (63%),
      CC 48 (89%) and DFA 30 (56%). Most virus isolations were in children aged 1-< 5
      years old and were associated with pneumonia in 39% and bronchopneumonia in 32%.
      SV assay showed a sensitivity and specificity of 68.8% and 99.7%, respectively,
      for detecting adenovirus from NPA. These results emphasize that CC assay is still
      important for the diagnosis of adenovirus, although SV and DFA are superior
      diagnostic assays.

PMID- 11284250
TI  - Infant mortality among Indonesian boys and girls: effect of sibling status.
AB  - The effect of gender and sibling status on the infant mortality rate (IMR) in
      Purworejo District, Central Java, Indonesia was investigated using direct
      estimation of IMR. A cohort of 1,948 infants born between 1 January 1995 and 31
      December 1996 was followed for 1 year within a surveillance system. IMR was
      higher (not significantly) in male infants, and males (but not females) had a
      higher mortality rate if born after more than two siblings. This was significant
      in the Highland area only. Mothers' education and quality of drinking water had
      no modifying effect in either sex on the association between IMR and sibling
      status. Thus, in contrast with studies from South Asia, there are no indications
      of preferential treatment of infant boys compared with infant girls in Central
      Java.

PMID- 11284251
TI  - Atypical presentations in children with post-neonatal tetanus in Ibadan, Nigeria.
AB  - In a retrospective review of 73 children with post-neonatal tetanus seen over an
      11-year period at University College Hospital, Ibadan, Nigeria, atypical portals
      of entry of the causative agent were recorded in nine and five developed unusual
      complications during the course of treatment for tetanus. Localized tetanus was
      encountered in seven children; this involved the cephalic region in one and one
      lower limb in each of the remaining six. Among these six children, the portal of
      entry of the organism included intramuscular injections into the buttock in five
      and an infected insect bite on the buttock in one case. Another unusual portal of
      entry, observed in two children, was through an impacted foreign body in the ear
      in the absence of otitis media. Arthritis of large joints was encountered in
      three children and two had episodes of severe bronchospasm which responded to
      bronchodilator treatment. The findings in this study significantly widen the
      reported spectrum of presentations and complications of tetanus in third-world
      children.

PMID- 11284252
TI  - Prolonged interferon alpha treatment in children with chronic hepatitis B.
AB  - Interferon alpha has been used widely to treat hepatitis B virus infection in
      children. However, the overall initial response rates have been < 50% and several
      strategies have been attempted to improve this. The aim of this study was to
      evaluate the safety and efficacy of prolonged interferon alpha treatment in
      children who did not respond to a previous course of interferon alpha treatment.
      Twenty-seven children with chronic hepatitis B who had not responded to a 6-month
      course of interferon alpha 2a (5 MU/m2 body surface) thrice weekly subcutaneously
      continued to receive interferon alpha at the same dosage for another 6 months
      without a rest phase. The children were followed for 6 months after completing 12
      months of therapy. All of them had HBsAg, HBV-DNA and HBeAg tested on completion
      of the first course. Six of the 27 (22.2%) cleared both HBV-DNA and HBeAg after
      completion of therapy and all six had a sustained response. Pre-treatment
      predictive factors were not significantly associated with treatment response. No
      adverse effect of interferon was seen during follow-up. We conclude that
      prolonged interferon treatment is well tolerated and leads to additional benefit.

PMID- 11284253
TI  - Giant omental cyst simulating ascites in a Nigerian child: case report and
      critique of clinical parameters and investigative modalities.
AB  - We report our experience of managing an 18-month-old boy in whom a giant omental
      cyst of 4.6 kg, which constituted 42% of his pre-operative weight, masqueraded as
      massive ascites. Pre-operative diagnosis and early surgical intervention were
      facilitated by inter-disciplinary collaboration, ultrasonography and radiological
      contrast studies. The differential diagnoses and treatment options of omental and
      mesenteric cysts are discussed. The importance of ultrasonography as an initial
      imaging tool for arriving at the correct diagnosis in a child with ascites of
      obscure aetiology is emphasized.

PMID- 11284254
TI  - Splenic tuberculosis presenting as hypersplenism.
AB  - A 9-year-old girl with a 5-6-month history of abdominal distension and fever was
      found to have massive splenomegaly with features of hypersplenism. Apart from a
      strongly positive Mantoux test, all investigations for massive splenomegaly
      proved negative. Splenectomy was carried out and histopathological examination of
      the spleen revealed granulomatous lesions suggestive of tuberculosis. The child
      improved after splenectomy and anti-tuberculous therapy and is doing well on
      follow-up. Splenic tuberculosis should be considered as an unusual cause of
      massive splenomegaly and hypersplenism.

PMID- 11284255
TI  - Septic arthritis of the hip caused by Salmonella typhi.
AB  - We describe septic arthritis of the hip in a child with typhoid fever. The
      aetiological diagnosis was confirmed by a positive Widal test as well as by
      isolation of Salmonella typhi from joint aspirate. Treatment with ceftriaxone
      along with surgical drainage was successful.

PMID- 11284256
TI  - Necrotizing fasciitis of the scalp in a neonate.
AB  - We report an 11-day-old baby who presented with necrotizing fasciitis of the
      scalp from which Escherichia coli was cultured. Treatment consisted of
      administration of parenteral broad-spectrum antibiotics and debridement. Skin
      grafting of the resulting scalp defect was not permitted by the parents. The
      wound healed with scar tissue over 3 months.

PMID- 11284257
TI  - [86th SIO National Congress. Cagliari, May 25, 2000. Malignant epithelial tumors
      of the mouth. Discussion].

PMID- 11284258
TI  - [Head shaking test and low-frequency rotation-acceleration test: comparison of
      sensitivity and specificity].
AB  - In studying the vestibular-oculomotor reflex (VOR) in patients with equilibrium
      disorders, both active and passive methods are used and at different stimulation
      frequencies, particularly to evaluate vestibular compensation. The present study
      compares the sensitivity and specificity of the low-frequency pendular test and
      the HST in normal subjects and in subjects suffering from various vestibular
      pathologies but showing no signs of spontaneous nystagmus, even under optimal
      evaluation conditions (infrared videonystagmoscopy). These spontaneous nystagmus
      free subjects underwent a routine study including: case history, infrared
      videonystagmoscopy (HST with 2 Hz stimulation) and ENG recording (saccadic
      movement, smooth pursuit, OKN, VOR, VOR-fix during pendular stimulation at 0.05
      Hz and VOR after Fitzgerald-Hallpike heat stimulation). On the basis of the
      results the subjects were classified as follows: normal (N): case history free of
      any equilibrium disorders and all tests negative (122 cases; 8.1%); peripheral
      vestibular pathology (P): case history of equilibrium disorders and labyrinthine
      predominance (LP) in excess of 20% upon caloric testing (716 cases; 47.6%);
      central pathology (C): case history of equilibrium disorders and at least 3
      pathological results from among the following tests: saccadic movement, smooth
      pursuit, OKN, VOR-fix (226 cases; 15.0%); mixed pathology (M): with both signs of
      P and C (440 cases; 29.3%). The pendular test showed signs of directional
      dominance (DP) higher than 10% (normal limit) in 7 cases of N (5.7%), 308 P
      (43.0%), 33 C (14.6%) and 162 M (36.8%). DP was higher than 10% in 55.2% of the P
      and M cases with onset less than 1 month before, in 42.8% of those with onset
      within the year and in 37.2% of those with onset more than a year before. A
      pathological response to the HST was observed (characterized by a series of at
      least 3 nystagmus shakes after a maximum latency of 15 seconds) in 0 N (0.0%),
      378 P (52.8%), 4 C (1.8%) and 247 M (56.1%). The nystagmus seen was nearly always
      monophasic (92.5%), biphasic nystagmus was only seen in only a few cases (7.5%);
      moreover it was predominantly horizontal in nature (94.9%) while it was vertical
      in only a few of the C cases (5.1%). The HST proved pathological in 46.5% of
      those pathologies with onset less than 1 month before, in 55.8% of those with
      onset within the year and in 54.4% of those with onset more than a year before.
      In 213 of the cases presenting pathological response to the HST there was
      agreement between VOR DP at the pendular test and the direction of the nystagmus
      evoked by the HST: 138 P (74.6%), 0 C (0.0%), 75 M (68.2%): moreover there was no
      agreement in 83 cases. When the DP was lower than 10% at the pendular test, the
      HST proved pathological in 213 P (52.2%), 3 C (1.6%), 150 M (53.9%). Both tests
      gave negative results in 112 N (91.8%), 163 P (22.8%), 186 C (82.3%), 123 M
      (27.9%). In cases of peripheral vestibular deficit (P and M) the sensitivity of
      the rotoacceleration test was 40.7%, specificity 88.5%. The sensitivity of the
      HST was 54.1%, specificity 98.8%. The sensitivity of the association using both
      tests was 75.2%, specificity 85.7%.

PMID- 11284259
TI  - [Ablation therapy with gentamycin in the treatment of Meniere's disease].
AB  - Historically the therapy for untreatable Meniere's disease (Md) has been surgery:
      conservative (cochleosacculotomy and decompression or sacco-endolymphatic shunt)
      or radical (labyrinthectomy and vestibular neurectomy). A valid alternative to
      surgery is the use of ototoxic drugs such as aminoglycoside antibiotics based on
      the assumption that some of the drugs exert greater ototoxicity vs. the posterior
      labyrinth. The purpose of the present study was to verify a severe protocol for
      the intratympanic administration of gentamicin sulfate in the treatment of Md
      unresponsive to medical treatment. A total of 29 patients were recruited for the
      study, all suffering from monolateral Md with reduced or normal (i.e. not absent)
      vestibular reflectivity on the side involved. The protocol called for
      audiovestibular testing prior to the treatment cycle and then 7 days after the
      administration of each individual dose. The same treatment scheme was used in all
      patients: a weekly intratympanic injection of gentamicin, 16 mg/per dose, for a
      maximum of 2 or 3 treatments. Of these cases, 20 have been followed up for 2 or
      more years and these are described in the present study. The follow-up called for
      suspending treatment and then repeating the audiovestibular tests every six
      months. Equilibrium was fully controlled in 70% of the patients while control was
      substantial in 30%. Audiometry showed that the auditory threshold remained
      unchanged in 60% of the cases while it worsened in 20% and, surprisingly,
      improved in the remaining 20%. In two cases deafness arose after the second
      treatment. The vestibular tests showed an uncompensated areflexia on the treated
      side after the therapeutic cycle although, in all cases, this had been
      compensated by the time of observation at 24 months. Symptoms of deafness
      remained unchanged. In conclusion, with respect to other more invasive
      treatments, chemical labyrinthectomy is simpler to perform and has fewer side
      effects while producing analogous clinical results.

PMID- 11284260
TI  - [Indications for selective arterial embolization in the treatment of epistaxis].
AB  - After posterior packing has failed, the treatment of choice for severe, recurrent
      posterior epistaxis is arterial ligature, usually through a transantral approach
      to the Internal Maxillary artery (LTA) or selective percutaneous embolization
      (EP). The advantages and disadvantages of each technique are discussed by various
      Authors. A critical review of the literature brings to light the discrepancies
      between the results of various studies: in a series by Strong et al. and in a
      review of the literature EP proved more effective than LTA (90-94% vs. 85-89%).
      On the contrary, using personal data Cullen and Tami reported that the results
      are analogous. As regards complications, these proved slightly more frequent, but
      minor, with LTA while the rare complications with EP were more serious. The per
      patient costs fundamentally depend on the type of hospital management and the
      availability of a treatment center; the results of the various studies are not
      analogous in this regard. The specific indications for the choice of which
      technique to use include: LTA: ethmoid artery hemorrhage, severe arteriosclerosis
      of the carotid compartment and allergy to the contrast medium; EP: cardiovascular
      instability, severe anemia and all conditions which are contraindications for
      general anesthesia. In the cases studied by the Authors, of the total 203
      patients admitted to hospital for posterior epistaxis between May 1995 and
      November 1999, 12 (5.9%; on the average 2.6 pt/yr) showed values lower than those
      found at other Centers. A total of 13 EP procedures were performed and the result
      was positive (stopping the hemorrhage) in 11 (91.7%). In one post-traumatic case
      there was a recurrence which could not be controlled by EP and thus the Authors
      resorted to surgical ligature. All the patients underwent fibroscopy after the
      posterior packing was removed and before establishing the indications for EP. A
      full 50% of the patients treated showed arterial hypertension and in all patients
      except the one with multiple traumas, the pre-embolization angiography showed the
      presence of submucosal teleangiectasia in the site of the epistaxis. This report
      supports the hypothesis that, in the presence of triggering factors
      (hypertension, pregnancy), untreatable epistaxis is sustained by a submucosal
      vascular malformation. On the other hand, it also asserts that although the
      patient evaluation to determine the EP treatment was less invasive than that used
      in other Centers, it was able to identify the patients with this malformation,
      thus validating the clinical criteria used.

PMID- 11284261
TI  - [Antileukotrienes in the prevention of postoperative recurrence of nasal
      polyposis in ASA syndrome].
AB  - There is a high incidence of post-surgical recurrences of nasal polyps (NP) in
      patients suffering from the ASA Syndrome. The numerous theories as to the
      pathogenesis of the ASA Syndrome include an increase in lipoxygenase-mediated
      arachidonic acid metabolism, with the subsequent hyperproduction of leukotrienes
      (LT), and an inhibition of the cycloxygenase. Therefore, based on the information
      acquired on the immunobiological action mechanism of montelukast, a cysteinyl-LT
      receptor antagonist, it appeared worth testing the effectiveness of this
      substance in preventing post-surgical NP recurrences in a group of ASA Syndrome
      patients. After taking a case history, filling out a questionnaire scoring nasal
      symptoms, undergoing rhinoendoscopy and rhinomanometry, 40 patients suffering
      from ASA-Syndrome and NP (age range 30-72 years) were recruited for the study.
      They were uniformly classified according to Lund and Mackay using high resolution
      CT of the nose and paranasal sinuses performed after at least 1 month of nasal
      medical treatment. All the patients underwent microendoscopic anterior-posterior
      ethmoidectomy and bilateral maxillary antrostomy. After removing the nasal
      packing, the only treatment administered was 10 mg of montelukast/die for 6
      months, with the drug suspended for 1 months after the first 3 months of
      treatment. The monthly follow-up included rhinoendoscopy, rhinomanometry and the
      questionnaire to score symptoms. After the seventh month a new CT was performed
      and compared with the pre-operative CT. In a control group of subjects,
      homogeneous with the test group, momethasone furoate nasal spray was administered
      at a dose of 100 mcg per nostril/die and loratadin tablets 10 mg/die. The results
      obtained in the patients treated with montelukast were analogous with those
      obtained in the second group, and during follow-up all patients showed total
      absence of any local recurrence, good nasal patency and no significant nasal
      symptom score on the questionnaire. In no case did the comparative CT, performed
      after the seventh month, show any signs of recurrence. The patients taking the
      montelukast reported a significant reduction in the use of steroids and
      bronchodilator inhalants during the course of the study than did the second
      group; indeed the number of asthmatic episodes dropped and they reported an
      improvement in the quality of life. Based on these results, the authors suggest
      that the use of montelukast in the treatment of post-surgical NP recurrences in
      ASA Syndrome is possible and advisable, even in synergetic association with the
      treatment administered to the second group. The positive results also support the
      hypothesis of altered arachidonic acid metabolism and call attention to the role
      of cysteinyl-LT in the pathogenesis of the ASA Syndrome.

PMID- 11284262
TI  - [Videofluoroscopic study of deglutition in patients with multiple sclerosis].
AB  - Multiple sclerosis is a neurological disease that affects the I/II motor neurons
      of the CNS and its symptoms include oropharyngeal dysphagia. The onset and course
      of this dysphagia significantly conditions the progression of the disease. The
      present study evaluates the incidence on deglutition and type of alterations in a
      sampling of 10 multiple sclerosis patients of which 4 showed clinical signs of
      dysphagia. The results, obtained by combining quantitative (clinical severity)
      and qualitative (functional alterations) parameters showed that 9 of the 10
      patients (90%) presented radiological abnormalities in the progression of the
      bolus. The conclusion drawn is that the high prevalence of dysphagia in multiple
      sclerosis, even if not always manifest clinically, justifies drawing up a
      standard protocol for radiological evaluation and clinical follow-up in order to
      screen those patients at greater risk of pulmonary complications and delay them
      as long as possible.

PMID- 11284263
TI  - [Description of a particular case of the so-called Schmincke lymphoepithelioma
      and study of the correlation with Epstein-Barr virus].
AB  - For poorly differentiated rhinopharyngeal carcinomas, the clinical presentation
      (association with the Epstein-Barr virus, paraneoplastic syndromes, onset of
      lymphoma) and the histopathological features can be polymorphous and they can
      confound or delay diagnosis and preparation of an adequate treatment plan (radio
      chemotherapy). Often these neoplasms arise as clinically primitive laterocervical
      metastases, masked by clinical findings and a history that can lead to the
      mistaken diagnosis of systemic lymphoproliferative processes such as Hodgkin's
      disease. Here an observation of this type is presented in a young patient (19
      years old) who came under observation for a laterocervical tumefaction recurrent
      from a previous exeresis performed at another hospital and symptoms of serotine
      febricula, dysphagia and serology positive for the Epstein-Barr virus (EBV). The
      patient underwent surgery and then radiotherapy and has been under close post
      operative follow-up for two years. To date the patient's condition--both local
      and general--is good. The particular histology of the neoformation lies in the
      abundant infiltration of plasma cell and lymphocyte eosinophils, at times in
      blastic form. Moreover, elements with a large clear nucleus and evident nucleolus
      (Hodgkin-like) and scattered multinucleate Langhans-type giant cells can be seen.
      Immunohistologically the tumor cells markedly express for cytokeratin and the
      latent membrane protein (LMP1) of the Epstein-Barr virus (EBV) and show a high
      growth fraction. Under the electron microscope, the plurinucleate giant cells
      present large nuclei with morphology similar to that of tumor cells. The clear
      cytokeratin-positivity of the tumor elements and the histological and
      ultrastructural features mentioned led to the diagnosis of a massive metastasis
      from lymphoepithelial carcinoma, the Schmincke variant, plus EBV infection of the
      neoplastic cells. The authors conclude assuming that the particular granulomatous
      reaction is due to the host's reaction to the tumor cells, but also to the
      reaction to the viral antigens. In the former case we find an attempt to limit
      the carcinomatous process; in the latter it is a response caused by the EBV and
      is not, apparently, aimed at protecting against the neoplasm rather it
      facilitates the neoplastic process.

PMID- 11284264
TI  - [Retropharyngeal lymphadenopathy in patients with advanced stage squamous cell
      carcinoma of the oropharynx: report of 2 cases and review of the literature].
AB  - Drawing from two cases which came under observation, the authors consider the
      high incidence of retropharyngeal metastases in oropharyngeal carcinoma. The
      diagnosis is made on the basis of radiographic examinations such as CAT and NMR
      which reveal the increase in size, the presence of central necrosis of the
      lateral retropharyngeal lymph nodes and the asymmetry of the long neck muscle. In
      the presence of advanced oropharyngeal carcinoma, the treatment calls for
      dissection of this space, even when radiology does not show any evident
      involvement. Lymph node positivity worsens the prognosis. Because of the marked
      significance of this involvement, some authors have proposed further N staging.
      Adjuvant RT completes the therapeutic protocol for such patients.

PMID- 11284265
TI  - [Morpho-functional analysis of surgical outcome in different types of CO2 laser
      cordectomy].

PMID- 11284266
TI  - [Selective fasicular neurotomy for spastic equinovarus foot deformity in cerebral
      palsy children].
AB  - Spasticity is usually treated by rehabilitation, orthosis, chemical denervations,
      orthopaedic surgery and neurosurgery. Selective fascicular neurotomy is a
      neurosurgical procedure consisting in partial section of selected motor nerves
      innervating spastic muscles. Neurotomy is indicated in cases of localised
      disabling spasticity without musculotendinous shortening, resistant to chemical
      denervation and for which a motor nerve block with anaesthetic has given a good
      functional result. Neurotomy includes division of the afferent Ia and Ib fibers,
      unable to recover, leading to permanent disappearance of the spasticity.
      Neurotomy also includes section of the motor efferent fibers with transient
      paresis as a result. In adults, neurotomy provides functional improvement in 81
      to 97% of cases. In case of posterior tibial neurotomy, improved walking
      stability and a decrease in foot equinus and knee recurvatum is observed. In
      children, the risk of deformity recurrence seems higher because of motor axonal
      reinnervation: indications must therefore be carefully considered and
      rehabilitation provided after surgery.

PMID- 11284267
TI  - Snapping iliotibial band. Report of ten cases and review of the literature.
AB  - The authors performed a retrospective study on 10 young patients (11 hips)
      presenting with a tight iliotibial band resistant to nonsurgical treatment. The
      main symptoms were pain and snapping of the hip during running and strenuous
      brisk walking. Diagnosis was made by the exclusion of other pathology and the
      elicitation of the snap. Surgical treatment was performed in all these patients
      to aid physiotherapy. The main principle of management however remains stretching
      exercises. When surgery is required, the aim is to elongate the iliotibial band.
      In our series, we used Z-plasty of the band followed by repair of the fascia as
      described by Stainsby. Our postoperative rehabilitation was different from
      Stainsby's, however. We allowed early progressive full weight bearing in contrast
      to the two weeks bed rest adopted by Stainsby. Stretching exercises were started
      two weeks after surgery; this was active in the first four weeks. The results
      were good at a mean follow-up period of 12 months (range: 8 to 24 months). Scar
      sensitivity was a problem in three of these patients; this responded only
      partially to a desensitization program. CONCLUSION: A reasonable result can be
      obtained following Z-plasty of a tight and symptomatic iliotibal band. Surgery is
      required only occasionally and there are associated complications, which must be
      discussed with the patients, these being recurrence of symptoms and wound
      problems.

PMID- 11284268
TI  - Plating of femoral shaft fractures. A review of 15 cases.
AB  - The objective of this study was to define the role, indications and outcome of
      plating in femur shaft fractures. All femoral shaft fractures admitted and
      treated by the authors during a 2-year period were analysed. The authors
      personally treated a total of 135 femur fractures. Of these 135 fractures, 15
      (11%) were treated with primary plating. The femoral fractures were classified as
      grade I (n = 4), grade III (n = 3), grade IV (n = 4), grade V (n = 3), and grade
      VII (n = 1) (OTA classification). Three patients sustained open fractures (one
      grade I and two grade II, Gustilo and Anderson classification). Pelvic (6) or
      ipsilateral lower extremity injuries (4) occurred in 10 of the 15 patients. A
      total of 23 body areas were injured, most commonly the chest (n = 10), abdomen (n
      = 5), head (n = 6) and blood vessels (n = 3). There were no infections reported.
      Two implant failures were noted. Femur plating is a useful technique in
      polytrauma patients for specific indications where intramedullary nailing (IMN)
      may be contra-indicated or technically not feasible. Although the postoperative
      morbidity (ARDS, death) in our study seems to be lower after plating than after
      intramedullary nailing, the rate of complications of fracture healing (30%) is
      significantly greater with femur plating than with intramedullary nailing (12%).

PMID- 11284269
TI  - [Surgical treatment of distal femoral fractures using extra-medullary
      osteosynthesis].
AB  - Forty seven fractures of the distal femur treated by internal fixation using a
      supracondylar compression screw or blade plate were retrospectively evaluated
      regarding their radiological and functional results. Blade plates were used for
      all types of distal femoral fractures until 1992; their indications were
      subsequently restricted to simple supracondylar fractures whereas a compression
      screw was preferred for other types of fractures. Taking into account the
      condition of the patients before fracture, 85% good and very good results were
      achieved with both techniques. Malunions resulted in poor functional outcomes
      (50% good and very good results). Malunions were mainly observed in patients with
      complex fractures (90% of cases with malunion), which confirms the poor prognosis
      of comminuted fractures. Nonunions (65%) and infection (3%) resulted in poor
      functional results. The presence of a bony defect in the medial femoral cortex
      increases the risk of nonunion; bone grafting should be used in such cases. The
      recent use of a long femoro-femoral external distractor in a few patients has
      proved of value as it allowed to achieve accurate reduction and considerably
      eased fracture reduction and fixation.

PMID- 11284270
TI  - Histomorphometric analysis of the normal adult patella.
AB  - The patellae of 6 male and 2 female, 40 to 70 year-old individuals, who were
      healthy at the time of their violent death, were assessed by computer-assisted
      image analysis. The means of the bone density (percentage of bone in the
      respective field of interest) ranged from approximately 20% to approximately 30%
      in the central spongiotic zones, from approximately 40% to approximately 80% in
      the superior and inferior peripheral zones, and approximately 40% to
      approximately 60% in the subchondral zone. Bone densities were greatest in the
      lateral parts of the subchondral and spongiotic territories. The bony trabeculae
      were haphazardly distributed in the central spongiotic zones. They were commonly
      oriented vertically or parallel to the surface of the patella in the peripheral
      and subchondral zones. In conclusion, the histomorphometric data presented
      validate the rationale of reaming the articular aspect of the patella into a dome
      shaped configuration with preservation of a circumferential bony bulwark in the
      preparation for the implantation of a thick polyethylene-based component with a
      concave undersurface.

PMID- 11284271
TI  - Knee fusion--a new technique using an old Belgian surgical approach and a new
      intramedullary nail.
AB  - Knee arthrodesis is a useful procedure in difficult cases such as failed total
      knee arthroplasty, severe articular trauma, bone tumors, and infected knee
      joints. The most common techniques for knee fusion include external fixation and
      intramedullary nailing. Kuntscher's nail is driven antegrade from the
      intertrochanteric region into the knee. We describe a new technique for knee
      arthrodesis using a new intramedullary nail and an old Belgian surgical approach
      to the knee joint published by Lambotte in 1913. This approach provides excellent
      exposure for the implantation of the nail by osteotomizing the patella
      vertically. The nail is implanted using HeyGroves method, whereby the nail is
      inserted retrograde into the femur and pulled distally anterograde into the
      tibia. We now use this technique as our standard procedure for knee fusion.

PMID- 11284272
TI  - Metastatic fractures of the tibia.
AB  - Pathologic fractures of the tibia due to a metastasis are rare. The treatment of
      an established fracture is sometimes conservative, but more often surgical. The
      purpose of the surgical procedure is to improve the quality of life and the
      ambulatory status, to relieve pain and to facilitate activities of daily living
      and nursing care. Four cases of operatively managed metastatic fractures of the
      tibia are presented with emphasis on the surgical technique. The scarce
      literature on metastatic tibial fractures in reviewed. The operative technique to
      be used does not only depend on the location of the tumor but also on the primary
      tumor, the response to adjuvant therapy and the life expectancy. For metastatic
      shaft fractures an intramedullary nail, sometimes augmented with bone cement, is
      preferred. For distal or proximal fractures a compound osteosynthesis with plates
      and screws offers a good solution. In the epiphyseal and metaphyseal region of
      the tibia an amputation or a tumor prosthesis is the procedure of choice.

PMID- 11284273
TI  - [Long term results in treatment of residual hip dysplasia by Salter osteotomy
      (study of 31 cases)].
AB  - Thirty-five hips (31 children, operated between 1971 and 1982) were reviewed
      after skeletal maturity with a mean follow-up of 12 years. The 31 children had
      been treated initially by closed reduction of the hip using the Somerville-Petit
      method (mean age: 18 months), and subsequently by innominate osteotomy (mean age:
      4 years) to correct a residual dysplasia which was graded upon the VCE angle, and
      Severin and McFarland's classifications. There were 88% good results; however
      only 51% of hips were classified Severin Ia and McFarland 1. In this study, the
      authors tried to assess the long term efficacy of the innominate osteotomy and to
      determine the optimal time to perform it. They discuss the limits of indications
      for innominate osteotomy, which could be excessive if spontaneous improvement may
      be expected to occur. Age and radiological findings are good indicators.

PMID- 11284274
TI  - [Complete transverse fractures of the talus: value of magnetic resonance imaging
      for detection of avascular necrosis].
AB  - The authors report a series of 32 complete transverse fractures of the neck or
      body of the talus. The fractures occurred mostly in young males, as a result of
      motor vehicle accidents. The fracture line was transverse in the neck or body of
      the talus in 20 cases, sagittal in four and comminuted in eight cases. Using
      Hawkins' classification, there were 10 type I, 16 type II, and 6 type III
      fractures. The treatment was conservative in 8 cases and surgical in 24. The
      patients were evaluated clinically and radiologically with an average follow-up
      of 7 years. All patients underwent radiological study at follow-up and 17
      underwent NMR evaluation. Eleven underwent NMR evaluation at final follow-up, and
      the other 6 early in their postoperative evolution. The postoperative results
      were evaluated based upon clinical and radiological criteria. The clinical result
      was good or very good in 37.5% of cases. Segmental necrosis of the talar body was
      noted in 6 cases and complete necrosis in 5, which required arthrodesis in 8
      cases. Avascular necrosis is a common complication. Its frequency depends on the
      type and displacement of the fracture. If it becomes symptomatic, the only
      treatment is tibiotalar or tibiotalocalcaneal arthrodesis. The contribution of
      NMR is very important, as it gives the positive diagnosis as well as information
      regarding evolution. Complete transverse fractures of the talar neck or body are
      rare; their treatment only gives a little over one third good and very good
      results in the long term. NMR gives the diagnosis early and shows the extent of
      necrosis. It can have predictive value for the collapse risk and guide
      reeducation with or without weight bearing.

PMID- 11284275
TI  - [Triple fracture of the superior shoulder suspensory complex].
AB  - The authors present the case of a displaced fracture of the coracoid process
      associated with a displaced fracture of the acromion, an undisplaced fracture of
      the clavicule and fractures of the first to fifth ribs. Open reduction of the
      coracoid process fracture was performed. At the last follow-up, the coracohumeral
      distance was restored (10 mm), but the acromiohumeral distance in the sagittal
      place was decreased (5 mm). The authors recommend open reduction of displaced
      fractures around the rotator cuff to limit the risk of impingement between the
      cuff and the coracoid process or the acromion.

PMID- 11284276
TI  - Brachial artery injury in closed posterior elbow dislocation case report.
AB  - The authors describe a case with a closed posterior elbow dislocation associated
      with a distal radial fracture and complete transsection of the brachial artery.
      The patient had a pulseless distal upper extremity and immediate gross swelling
      of the elbow and forearm. As closed reduction was not possible, open reduction
      had to be performed through an anteromedial approach to the elbow. End-to-end
      suture of the brachial artery was successful. After fasciotomy and internal
      fixation of the distal radial fracture, the elbow was stabilized with an external
      fixator spanning the elbow joint. After two years, despite good function of the
      elbow, restoration of the hand function is not optimal owing to persistent motor
      deficit of the ulnar nerve.

PMID- 11284277
TI  - Anterior interosseous nerve injury associated with a Monteggia fracture
      dislocation.
AB  - A case of an anterior interosseous nerve palsy associated with a Monteggia
      fracture-dislocation is presented. The fracture of the ulna was reduced and
      stabilized with a plate, and the proximal radioulnar dislocation was also
      reduced. The nerve recovery was spontaneous and complete. A satisfactory result
      was obtained, without pain or functional sequelae.

PMID- 11284278
TI  - Kienbock disease in cerebral palsy.
AB  - A 48-year-old woman with cerebral palsy (CP) and lunatomalacia in her paralytic
      arm is reported. We performed a proximal row carpectomy with good pain
      resolution. One should be aware of this association in a CP patient complaining
      of wrist pain.

PMID- 11284279
TI  - An uncommon injury of the thumb.
AB  - Ulnar collateral ligament rupture of the thumb is a relatively common injury that
      is often missed in the emergency department. This in combination with an
      interphalangeal joint dislocation of the ipsilateral thumb is rare and we report
      such a case. The importance of looking specifically for an associated ulnar
      collateral ligament laxity in any injury to the thumb is highlighted. The force
      producing a combination of ulnar collateral ligament rupture with ipsilateral
      simultaneous injury to the thumb is often severe enough to cause complete rupture
      of the ligament, necessitating open repair.

PMID- 11284280
TI  - Unusual presentations in myositis ossificans progressiva. A case report.
AB  - Myositis ossificans progressiva is a rare connective tissue disorder. We present
      here a case of myositis ossificans progressiva with some unusual presentations
      and associated congenital skeletal anomalies that are reported very infrequently
      in the literature. The case report highlights the importance of early diagnosis
      in a case of rapidly progressive myositis ossificans progressiva.

PMID- 11284281
TI  - [Suspected amyotrophic lateral sclerosis? Don't forget diagnostic imaging of the
      spine].
AB  - Two patients, men aged 35 and 72 years, had progressive muscle weakness, lower
      motor neuron signs in all extremities and upper motor neuron signs in the legs.
      There were no major sensory signs on examination. The clinical picture very much
      resembled amyotrophic lateral sclerosis (ALS), although there were never brain
      stem signs. Myelopathy and polyradiculopathies caused by a tandem cervical and
      lumbar spinal stenosis explained the clinical picture. Cervical MRI and lumbar CT
      confirmed this diagnosis. Laminectomy was done, after which both patients
      remained with unchanged symptoms. Tandem spinal stenosis should be part of the
      differential diagnosis of ALS. Imaging of the spine is necessary to confirm this
      diagnosis, and in the absence of bulbar signs always necessary prior to the
      diagnosis of ALS.

PMID- 11284282
TI  - [Evaluation of the Dutch Medical Treatment Act (WGBO)].
AB  - Five years after its implementation, the Dutch Medical Treatment Act, which
      regulates the doctor patient contract, was evaluated in an extensive study. This
      act regulates (a) the right of patients to be informed and to give consent and
      (b) how to deal with confidential patient data. The main outcome from this study
      is that, in general, physicians are aware of the most important patient rights
      laid down in the Act and that compliance with these is mostly satisfactory.
      Nevertheless, the implementation can still be improved in several areas, notably
      the application of the more abstract provisions of the Act in everyday practice.
      It is recommended that measures be taken in the education and further training of
      health professionals and that guidelines are developed that detail how to deal
      with the rights of a patient in specific situations.

PMID- 11284283
TI  - [Evaluation of the Dutch Medical Treatment Act, five years after implementation:
      subjective and poorly substantiated].
AB  - Five years after its implementation, the Dutch Medical Treatment Act, which
      regulates the doctor-patient contract, was evaluated. Two subjects were
      investigated: the right of the patient to be informed and to give informed
      consent and the way physicians deal with personal information. From a
      methodological point of view, this appraisal was very disappointing. At best, the
      evaluation report is descriptive but not evaluative: no comparative study was
      carried out before and after the law was implemented to ascertain effects. The
      Act is difficult to evaluate in practice as its goal, improving the legal
      position of the patient, is dogmatic. Its regulations on informed consent and
      agreement as well as the rules of law concerning the use of patient data for
      clinical research, have at times proved to be impractical even though such legal
      directives appear to be reasonable. The problems addressed by this law should be
      more widely debated and be subjected to a far more rigorous validation process.

PMID- 11284284
TI  - [Suicidality].
AB  - Prevention of suicidal behaviour remains difficult, despite increasing knowledge
      of its determinants. Health service efforts hardly affect suicide rates. Recent
      shifts in the epidemiology of suicidal behaviour are rising rates among the young
      and increasing use of violent methods; these can be linked to emerging
      aetiological insights. Early stages of the suicidal process often manifest
      themselves at an early age, as emotional and behavioural instability.
      Epidemiological evidence suggests that the suicidal process increasingly
      concentrates itself in a vulnerable minority in whom it progresses rapidly to a
      phase of relative unresponsiveness to environmental influences including
      preventive efforts. Thus, prevention should focus not only on persons in the
      later stages of the suicidal process like psychiatric patients, but especially on
      individuals who, as youngsters, show signs of entering its very first stages.
      Since high suicide risk implies high risk of other adverse health outcomes as
      well, this should, in time, yield health gains in more domains than suicide
      reduction only.

PMID- 11284285
TI  - [Screening for lung cancer in the Netherlands: the role of spiral CT scan].
AB  - The very poor prognosis of lung cancer has barely changed in the last two decades
      despite all efforts. However, prognosis is better when the disease is detected
      earlier, so that curative surgery or radiotherapy can be applied. Lung cancer
      screening in the past by chest X-ray did not lead to a decrease in lung cancer
      mortality, because the chest X-ray has low sensitivity for early invasive stages.
      With the advent of the low-dose spiral CT scan it has become feasible to detect
      early invasive stage I lung cancer in 80-90%. Modern screening for lung cancer by
      spiral CT scan could possibly decrease lung cancer mortality. Despite the first
      favourable results of screening the question remains whether lung cancer
      screening will be cost-effective. These questions can only be resolved in a
      randomised controlled trial with lung cancer mortality as unbiased end-point.
      Such a study should be initiated in the Netherlands, a country with large
      experience in screening trials and a good health care system. Only after lung
      cancer screening has proven to be cost-effective can appropriate implementation
      be recommended to prevent uncontrolled and opportunistic diffusion of this new
      screening technique into clinical practice in the near future.

PMID- 11284286
TI  - [Side effects of sildenafil: findings from two years practical experience].
AB  - Sildenafil has been registered for the treatment of erectile dysfunction since
      1998. World wide a large number of patients were reported, dying of acute heart
      disease after using sildenafil. Therefore the patient instruction text was
      adapted. Simultaneous use of sildenafil and nitrates is contraindicated because
      of serious decrease of the blood pressure. The use of sildenafil can lead to
      physical stress in patients with a history of heart disease and a treadmill test
      assessment is advisable. In two years 38 adverse reactions were seen in 25 Dutch
      patients. The Dutch reports (three cardiovascular deaths since the introduction)
      also show the dilemmas in the assessment of the safety of sildenafil: is it the
      underlying disease or is it the drug that causes death? Further research into the
      adverse reactions has to be done, therefore reporting suspected side effects of
      sildenafil is important.

PMID- 11284287
TI  - [Diagnostic image (29). Adult form of proximal spinal muscular atrophy].
AB  - A 58-year-old man developed slowly progressive weakness of both legs due to the
      adult form of proximal spinal muscular atrophy.

PMID- 11284288
TI  - [Significance of letters published in the Dutch Journal of Medicine, 1997/98].
AB  - OBJECTIVE: To determine whether in the correspondence section of the Nederlands
      Tijdschrift voor Geneeskunde (Dutch Journal of Medicine, NTvG) serious criticism
      is formulated or important mistakes in the original articles are pointed out.
      DESIGN: Descriptive, retrospective bibliometric study. METHOD: Correspondence in
      the period July 5, 1997-June 27, 1998 published in the NTvG (n = 196 letters) was
      scored for 10 items and categorized in categories: 'agree', 'do not agree'
      (criticizing methods or results or interpretation, or unmotivated criticism) and
      'political reaction'. The questions were studied to what category of published
      articles the letters referred and how many letters referred to the same articles.
      22 letters from the period October-December 1998 were judged separately as the
      peer review reports of the original articles were still available. RESULTS: In
      115 (58.7%) letters the writers expressed agreement with the original article.
      Almost 40% (77) of the 196 letters contained scientific discussion on the subject
      in question. Most reactions concerned 'Original articles' (25%) and 'Clinical
      lessons' (19.4%). In 8/196 (4.1%) a mistake was revealed; 6 of these reactions
      led to the publication of a 'Correction' (to 3 articles). There was no criticism
      which would have led to rejection of the article involved had it been known
      before publication. The letters about articles of which the peer reviews were
      still available contained no criticism of points the peer reviewers had missed.
      CONCLUSION: Of the correspondence letters of the NTvG 4.1% contained scientific
      criticism which could have led to changes in the article if it had been known
      before publication.

PMID- 11284289
TI  - [Tubercular granulomas of the liver in a Somalian patient notwithstanding a
      chronic hepatitis C].
AB  - A 44-year-old male Somalian immigrant was admitted to hospital for evaluation of
      upper abdominal pain and painful joints (neck and shoulders). Chronic active
      hepatitis caused by hepatitis C virus was diagnosed. Further examination was
      instituted because of the simultaneous finding of granulomas in a liver biopsy.
      In hepatitis C liver granulomas may be found. Infection by Mycobacterium
      tuberculosis was established, however, after extensive investigation. Treatment
      was started with tuberculostatic drugs, after which the complaints of the patient
      disappeared, liver enzyme levels decreased and granulomas in the liver
      disappeared. No side effects of the tuberculostatic treatment were seen on the
      course of the hepatitis C.

PMID- 11284290
TI  - [Lithium intoxication due to simultaneous use of trimethoprim].
AB  - A 40-year-old woman with a schizoaffective disorder was, inter alia, receiving
      lithium carbonate. During a simultaneous treatment with trimethoprim, she
      experienced symptoms of nausea, a feeling of malaise, concentration problems,
      trembling, an uncertain gait, diarrhoea and muscle spasms, without fever. The
      lithium level appeared to be elevated. The only cause of the intoxication
      indicated was the simultaneous use of trimethoprim. Following clinical
      rehydration, the patient made a good recovery. Trimethoprim has the same effect
      on the kidney as amiloride, a potassium-sparing diuretic, for which it is known
      that its combined use with lithium can result in an elevated lithium level.

PMID- 11284292
TI  - [Psychiatric case history of Vincent van Gogh].

PMID- 11284293
TI  - [Psychiatric case history of Vincent van Gogh].

PMID- 11284294
TI  - [Psychiatric case history of Vincent van Gogh].

PMID- 11284295
TI  - Impact of microarray technologies on cytopathology. Overview of technologies and
      commentary on current and future implications for pathologists and
      cytopathologists.

PMID- 11284296
TI  - Cytoarchitectural findings in the diagnosis of primary soft tissue tumors.
AB  - OBJECTIVE: To review the major cytologic and architectural criteria in the
      diagnosis of primary soft tissue tumors, highlighting the importance of clinical
      correlation and the value of ancillary methods. STUDY DESIGN: Given the variety
      and complexity of clinicopathologic entities, the initial approach is based on
      pattern analysis. Six basic categories are established as a function of cell
      shape, stromal characteristics and resemblance to normal tissue. RESULTS: First,
      in myxoid-rich matrix tumors, special attention should be paid to lipoblasts,
      ganglion type, stellate cells and metachromatic fibrillar matrix. Second, in
      round cell tumors the following cytoarchitectural findings are of special
      interest: atypical rhabdomyoblasts, atypical lipoblasts, neuroblast rosettes,
      cytoplasmic glycogen, melanin pigment, islets of mature cartilage, hyaline
      cytoplasmic inclusions and fragments of connective tissue closely associated with
      round cells. Third, in spindle tumors the most important cytoarchitectural
      findings are: biphasic cellularity; elongated, buckled or wavy, tapered nuclei;
      nuclear palisades; straight, elongated, blunt-ended nuclei; melanotic pigment;
      storiform pattern; tissue fragments with collagen fibers or degenerated elastin;
      intracytoplasmic hyaline globules; and scattered spindle cells in a background of
      red blood cells. Fourth, in pleomorphic tumors specific typing is often
      difficult, if not impossible, since cells display few or no differential
      features. Fifth, in epithelial like cell tumors the cytologic findings of major
      diagnostic interest are: melanin deposits, crystalline inclusions,
      intracytoplasmic lumina, anisonucleosis and nuclear cytoplasmic inclusions. Last,
      in maturelike cell tumors, the architectural pattern resembles that of mature
      tissues. CONCLUSION: Although cytologic analysis of primary soft tissue tumors is
      hampered by the paucity of diagnostic findings, the establishment of
      clinicocytologic correlations, taking into account architectural patterns,
      cytologic details and clinical characteristics of the lesion, allows precise
      diagnosis of a significant number of tumors. Application of new techniques
      (immunocytochemistry, electron microscopy and cytogenetics) to cytologic
      aspirates has prompted a substantial reduction in the number of doubtful
      clinicocytologic diagnoses and considerably broadened the diagnostic spectrum.

PMID- 11284297
TI  - Significance of tissue fragments in voided urine specimens.
AB  - OBJECTIVE: To determine the diagnostic significance of tissue fragments in voided
      urine specimens. STUDY DESIGN: We reviewed all the voided urine specimens
      collected and processed by the Millipore filter technique (Bedford,
      Massachusetts, U.S.A.) at our institution between January 1, 1997, and December
      31, 1998, and the corresponding biopsies obtained within 120 days after urine
      examination. The type and number of tissue fragments were correlated with the
      histologic diagnosis and clinical features; the results were compared to those
      from a recently published study. RESULTS: Of the 2,553 voided urine specimens
      examined, 174 (7%) had corresponding biopsies. Cell groups (tissue fragments)
      consisting of either flat sheets or three-dimensional structures were
      significantly more common (57%) (chi 2 P < .005) in urine specimens with biopsies
      revealing urothelial malignancies than in negative biopsies (6%). Three
      dimensional groups were also statistically more common in cases with invasive
      transitional cell carcinoma. Proper identification of tissue fragments was highly
      significant and correlated with urothelial neoplastic changes. CONCLUSION: The
      results of the present investigation using the Millipore filter technique for
      voided urine cytology processing, differed from those of a recently published
      study that employed cytocentrifugation. Tissue fragments, to be differentiated
      from groups, clumps or clusters that often result from centrifugation and other
      concentration artifacts, were strongly associated with urothelial neoplasia,
      uncommonly with nonneoplastic disease processes affecting the urinary tract but
      always with urothelial disease.

PMID- 11284298
TI  - Significance of cytologically normal endometrial cells in cervical smears from
      postmenopausal women.
AB  - OBJECTIVE: To determine the significance of cytologically normal endometrial
      cells in cervicovaginal (CV) smears from postmenopausal women over age 55 years.
      STUDY DESIGN: From January 1995 to January 1998, 220 women had CV smears
      demonstrating cytologically normal endometrial cells. The menopausal status,
      hormone replacement therapy (HRT) and information related to subsequent CV smears
      and endometrial sampling within 12 months of the initial diagnosis was recorded.
      RESULTS: Eighty-one of the 220 cases (36.8%) had histologic sampling of the
      endometrium. Thirty-four of 81 (42%) showed no endometrial pathology. Endometrial
      pathology was identified in 28 of 81 (34%), of which 19 were endometrial polyps
      (23.4%), 4 were endometrial hyperplasia (4.9%), 4 were endometrial carcinoma
      (4.9%) and 1 was a leiomyoma (1.2%). Nineteen (23.4%) were insufficient for
      diagnosis. Ninety-one of 220 women were on HRT, and 129 were not. In the group
      without HRT, endometrial disease was identified in 22/51 (43%) cases as compared
      to 6/30 (20%) in the group with HRT (P < .001). Endometrial carcinoma was
      identified in three (5.8%) cases and one (3.3%) case without and with HRT,
      respectively. CONCLUSION: Although the finding of normal endometrial cells in Pap
      smears from postmenopausal women was without any clinical significance in the
      majority of women in this study, in a small number it was associated with
      endometrial hyperplasia and carcinoma. Women who were not on HRT had a higher
      incidence of endometrial pathology.

PMID- 11284299
TI  - Evaluating the accuracy of uterine cancer screening with the regional cancer
      registration system.
AB  - OBJECTIVE: To evaluate the effectiveness of uterine cancer screening by analyzing
      the accuracy of cervical and endometrial cytodiagnoses as screening methods.
      STUDY DESIGN: During the year of April 1, 1991-March 31, 1992, 186,161 and 5,697
      women underwent cervical and endometrial cytodiagnoses, respectively, and their
      cytodiagnostic results were computer registered at the Miyagi Cancer Society. By
      comparison of these examinees with 753 cancer patients who were registered at the
      regional cancer registry between 1991 and 1993, 133 individuals who were assumed
      to be identical between the two systems were selected, and of these cases, 83
      patients, including test-positive cases, were found within one year. The
      sensitivity and specificity of each screening method were investigated. RESULTS:
      Regarding examinees diagnosed as having cancer by the same month in the following
      year after diagnosis on screening as false negative, the sensitivity, specificity
      and false negative rates of cervical cytodiagnosis were 94.7%, 98.9% and 5.3%,
      respectively, and those of endometrial cytodiagnosis were 83.3%, 96.7% and 16.7%,
      respectively. CONCLUSION: In comparison with the accuracy of cancer examinations
      for other organs performed by the health care administration, the accuracy of
      cervical and endometrial cytodiagnoses was sufficient to designate them screening
      methods.

PMID- 11284300
TI  - Atypical glandular cells of undetermined significance in cervical smears after
      conization. Cytologic features differentiating them from adenocarcinoma in situ.
AB  - OBJECTIVE: To evaluate the cytologic features of atypical glandular cells of
      undetermined significance (AGUS) smears following conization through a comparison
      with adenocarcinoma in situ (AIS) smears. STUDY DESIGN: Fifty cervical smears,
      diagnosed as AGUS based on groups of crowded glandular cells that raised the
      possibility of AIS, from 38 patients who had conization and 24 AIS smears,
      histologically confirmed, from 17 patients were reviewed. Subsequent follow-up
      biopsies or hysterectomies in 38 patients were evaluated. RESULTS: Nuclear atypia
      was a more reliable feature than architectural structure in differentiating
      postcone effect from AIS on cytology. The predominant cytologic features of the
      postcone smears were crowded glandular cells with a high nuclear/cytoplasmic
      ratio and relatively small, hyperchromatic nuclei with rather finely granular and
      uniformly dispersed chromatin, less distinct nuclear membranes, less frequent
      mitosis and presence of endometrial-type stromal cells in the background. The
      architecture of the crowded cells in the postcone smears was sometimes similar to
      that of AIS. No AIS or high grade squamous intraepithelial lesion histology was
      encountered in follow-up biopsies or hysterectomy specimens. CONCLUSION: The
      cytologic features distinguishing AGUS from AIS may be helpful in identifying the
      postcone effect. Since it is important to avoid miscalling the postcone effect as
      AIS, it is recommended that one check for a previous history of a cone biopsy.

PMID- 11284301
TI  - Detection of N-myc amplification in neuroblastomas using Southern blotting on
      fine needle aspirates.
AB  - OBJECTIVE: To verify the possibility of detecting N-myc amplification in fine
      needle aspiration (FNA) cytology from neuroblastomas by the Southern blotting
      technique. STUDY DESIGN: Fifteen neuroblastomas diagnosed by FNA in the
      Department of Pathology, Hospital de S. Joao, between 1990 and 1998, were studied
      for N-myc amplification using the Southern blotting technique in cytologic and
      histologic material. RESULTS: DNA extraction from the cytologic material was
      performed in all cases (N = 15). In two cases the quality/quantity of the DNA did
      not allow the study of N-myc status by the Southern blotting technique. We
      detected N-myc amplification in 1 of 13 patients (7.6%) from whom material was
      available for genetic study. CONCLUSION: It is possible to use the Southern
      blotting technique to demonstrate N-myc amplification in material obtained from
      FNA of neuroblastomas.

PMID- 11284302
TI  - Worrisome histologic alterations following fine needle aspiration of the thyroid.
AB  - OBJECTIVE: To investigate worrisome histologic alterations following fine needle
      aspiration (FNA) of the thyroid (WHAFFT). STUDY DESIGN: Of 1,890 FNA thyroid
      cases, 265 underwent surgical excision. The histologic sections of these cases
      were studied for WHAFFT lesions. Thirty control cases were also studied. RESULTS:
      WHAFFT lesions were present in 38.49% of cases. Acute lesions were seen in 30 and
      chronic in 72 cases. Control cases did not show WHAFFT lesions. The common
      lesions were hemorrhage and fibrosis. Worrisome lesions, like nuclear atypia,
      vascular changes, capsular pseudoinvasion and metaplasia, were present in 32
      (12.07%) cases. CONCLUSION: Considering the large number of FNAs and reduction in
      the number of thyroid excisions, the advantages of FNA are manifold as compared
      to the few diagnostic problems. Misdiagnosis can be avoided with awareness of
      WHAFFT lesions.

PMID- 11284303
TI  - Application of Ultrafast Papanicolaou stain to body fluid cytology.
AB  - OBJECTIVE: To investigate the applicability of the Ultrafast Papanicolaou stain
      to the cytology of fluids and to compare it with other methods. STUDY DESIGN:
      Over a 30-month period, 528 unfixed fluids (462 serous effusions, 48 pelvic
      washings, 16 cyst fluids and 2 bile duct drain fluids) were mixed thoroughly and
      centrifuged. Two Swedish-style air-dried smears were made and stained with Diff
      Quik (Mercedes Medical, Inc., Sarasota, Florida, U.S.A.) and Ultrafast
      Papanicolaou stain (Richard Allan Scientific, Kalamazoo, Michigan, U.S.A.), and
      the remaining sediment was fixed in CytoRich Red (TriPath Imaging, Inc.,
      Burlington, North Carolina, U.S.A.), centrifuged onto a 17.5-mm circle with a
      Hettich cytocentrifuge and stained by the Papanicolaou method. RESULTS: For the
      115 malignant fluids, Ultrafast Papanicolaou stain was the preferred method in
      the 94 non-hematopoietic malignant fluids, Diff-Quik was the preferred method in
      the 9 hematopoietic malignancies, and CytoRich Red was the preferred preparation
      in 8 bloody effusions containing rare cancer cells and 4 malignant pelvic
      washings. The diagnostic turnaround time of smears stained by Ultrafast
      Papanicolaou stain was < 15 minutes, fast enough for intraoperative
      consultations. CONCLUSION: It seems that Ultrafast Papanicolaou stain improves
      the resolution of cytoplasmic and nuclear details of nonhematopoietic cells in
      body fluids. However, to detect cancer in all types of fluids, Diff-Quik and
      CytoRich preparations are also required. We now examine three slides per fluid
      sample, one slide by each of the three techniques.

PMID- 11284304
TI  - Cytomorphology of filariasis revisited. Expansion of the morphologic spectrum and
      coexistence with other lesions.
AB  - OBJECTIVE: To review the cytomorphologic spectrum of the filarial worm and
      associated tissue response in 33 cases. STUDY DESIGN: Retrospective analysis was
      carried out in clinically unsuspected cases of filariasis diagnosed on cytology
      over a period of 10 years. Twenty-nine aspirate smears from 28 patients were air
      dried and stained with May-Grunwald-Giemsa stain. Four routine cervical smears
      and one centrifuged smear of urine were stained with Papanicolaou stain. RESULTS:
      Microfilariae alone and along with adult gravid females were present in 25 and 4
      cases, respectively. In one case both adult male and female worms with
      microfilariae and eggs were seen. The diagnosis was based on the presence of eggs
      alone in one case and fragments of female worms in two. Four of these cases were
      neoplastic lesions, and microfilariae were found incidentally. In one case of
      splenomegaly microfilariae were seen along with Leishman-Donovan bodies.
      CONCLUSION: Filariasis can be diagnosed on cytology by demonstrating
      microfilariae, a male or female worm, or eggs alone. It can be seen in
      association with neoplastic lesions and rarely with other parasitic infections.

PMID- 11284305
TI  - ASCUS, mature metaplastic type. Cytologic diagnosis and follow-up.
AB  - OBJECTIVE: To study the cytologic criteria for follow-up of mature metaplastic
      cells within the atypical squamous cells of undetermined significance (ASCUS)
      category. STUDY DESIGN: Squamous epithelial abnormalities between January 1994
      and June 1997 at our institution totaled 2,632 and included squamous carcinoma
      (1), high grade squamous intraepithelial lesions (278), low grade squamous
      intraepithelial lesions (875) and ASCUS (1,478). From the ASCUS group, 134
      (9.06%) were metaplastic; 89 were selected for review. Criteria for case
      selection were follow-up with tissue biopsy or at least two Pap smears and no
      previous epithelial abnormality. Patients ranged from 27 to 70 years of age.
      Parameters tabulated included number of abnormal cells per slide, their
      architecture, cell size, shape, cytoplasmic hue and texture, nuclear size and
      contour, chromatin pattern and nucleoli. Additionally, specimens were reviewed
      for hormonal status and inflammation. The findings were correlated with follow-up
      data. RESULTS: Cells generally appeared single or in loose, monolayered sheets of
      three to seven cells per group. The cells were well demarcated, polygonal or oval
      and ranged from 11 to 30 microns with cyanophilic or eosinophilic thickened
      cytoplasm. The round to oval nuclei with slight irregularity showed a minimally
      increased nuclear/cytoplasmic ratio with stippled chromatin. Upon review, 69
      smears were confirmed as ASCUS-M. Follow-up revealed 42 with benign findings, 9
      with persistent ASCUS/ASCUS-M and 18 with low grade squamous intraepithelial
      lesions. CONCLUSION: In mature metaplastic cells with minimal atypia in patients
      with no previous or concurrent dysplasia, the follow-up details were similar to
      those described for ASCUS-superficial/immediate squamous cells. These patients
      could be followed conservatively.

PMID- 11284306
TI  - Anitschkow nuclear changes in postmortem pericardial scrapings.
AB  - OBJECTIVE: To document the presence of Anitschkow nuclear changes (ANC) in
      pericardial mesothelium at autopsy after the incidental finding of ANC in
      pericardial scrapings from a fatal case of overwhelming sepsis. STUDY DESIGN:
      Fourteen, nonconsecutive autopsy cases were studied. Using the edge of a scalpel,
      the visceral pericardium from the left ventricle was scraped, and the sample was
      smeared onto glass slides, fixed in 95% ethanol, Papanicolaou stained and
      evaluated for the presence of ANC. Histologic correlation was also performed.
      RESULTS: ANC were observed in pericardial mesothelial cells in 6 of 14 cases.
      Sepsis was the cause of death in three. Fatal cardiac arrhythmia, T-cell lymphoma
      and fulminant hepatic necrosis were found in the remaining cases. While readily
      seen in cytologic preparations, ANC were found focally in only one case examined
      histologically. CONCLUSION: Postmortem cytologic evaluation provides information
      relevant to the autopsy. In this study, ANC were very clearly seen in six
      pericardial scrapings. Clinical correlation supports the current theory that ANC
      represent a nonspecific reactive cell change.

PMID- 11284307
TI  - Cervical Cytology Practice Guidelines. American Society of Cytopathology.

PMID- 11284308
TI  - Cytologic findings in a fetal intracranial teratoma. A case report.
AB  - BACKGROUND: Fetal neoplasms are very rare. Recently we had the opportunity to
      examine the fine needle aspiration (FNA) biopsy of a fetal intracranial teratoma.
      CASE: The tumor was found in a 30-week-gestation fetus; the mother was 32 years
      old, gravida 4, para 1. She presented with a rapid increase in abdominal girth
      over a two-week period. An ultrasound scan showed severe fetal hydrocephalus and
      a massive intracranial tumor thought to be a teratoma because of variations in
      echogenicity and spotty calcification. An FNA biopsy was performed under
      ultrasound guidance. It showed mainly neuroepithelial cells, so a differential
      diagnosis of malignant neuroepithelial tumor was considered. At autopsy, several
      other tissue types were found in the tumor, consistent with a teratoma.
      CONCLUSION: Advances in diagnosis of fetal anomalies by ultrasound have been
      associated with an increase in the use of fetal interventions performed in utero.
      This includes the availability of fetal surgery in some centers. FNA biopsy of
      fetal lesions does not appear to be well described. Increased experience with
      this technique is necessary if its full potential is to be realized.

PMID- 11284309
TI  - Fine needle aspiration biopsy of epithelioid angiomyolipoma. A case report.
AB  - BACKGROUND: Epithelioid angiomyolipoma (AMYL) is a variant of angiomyolipoma
      characterized by sheets of epithelioid cells that may mimic renal cell carcinoma.
      This is the first report describing the fine needle aspiration biopsy features of
      this lesion. CASE: A 47-year-old man with a history of epithelioid angiomyolipoma
      of the kidney treated with nephrectomy nine months previously presented with a
      recurrent retroperitoneal mass and multiple nodular liver lesions. Fine needle
      aspiration biopsy of one of the liver lesions showed fragments and sheets of
      noncohesive epithelioid cells with thin cytoplasm, markedly atypical nuclei, and
      scattered bizarre and multinucleated forms. The epithelioid cells focally
      expressed HMB-45 and were nonimmunoreactive, with epithelial markers. CONCLUSION:
      Epithelioid AMYL may pose differential diagnostic problems with high grade
      carcinoma, especially renal cell, hepatocellular and metastatic carcinoma. An
      awareness of this entity and its characteristic cytologic features and
      immunoreactivity with HMB-45 is helpful in its identification.

PMID- 11284310
TI  - Granulomatous angiopanniculitis of the breast. A case report.
AB  - BACKGROUND: Granulomatous angiopanniculitis (GAP) is a rare benign condition of
      the breast of unknown etiology. Clinically and by fine needle examination, GAP
      may simulate breast carcinoma. The cytologic characteristics have not been
      described before. CASE: A 63-year-old female exhibited a palpable mass in her
      left breast. The fine needle aspirate contained both epithelioid and stromal
      elements. The epithelioid component consisted of dissociated individual cells and
      small groups and clusters of atypical cells. The stromal component showed a
      uniform, not-atypical pattern. The lumpectomy specimen showed nonnecrotizing
      granulomatous panniculitis and lymphoid angiitis without involvement of ducts or
      lobules. CONCLUSION: Granulomatous lesions should be borne in mind in the
      differential diagnosis of breast cancer in fine needle aspiration cytology. GAP
      must be histopathologically distinguished from granulomatous inflammation in the
      breast of autoimmune or infectious origin as specific medical therapy may be
      available for these latter diseases.

PMID- 11284311
TI  - Lymphonodular cryptococcosis diagnosed by fine needle aspiration cytology in
      hyper-IgM syndrome. A case report.
AB  - BACKGROUND: Most cases of cryptococcosis are diagnosed when signs of meningitis
      have appeared. We report a case of lymphonodular cryptococcosis that was
      diagnosed by fine needle aspiration cytology (FNAC), excisional biopsy of a
      cervical lymph node and culture of aspirated material. CASE: An 11-year-old boy
      presented with a history of fever and enlarged bilateral cervical lymph nodes of
      two weeks' duration. Past medical history included immunoglobulin replacement for
      hyper-IgM syndrome for the previous eight years. FNAC smears from a cervical
      lymph node showed numerous yeasts of various sizes, ranging from 5 to 15 microns
      in diameter, located in the cytoplasm of multinucleated giant cells and in the
      background. In air-dried, Diff-Quik-stained slides, the yeasts stained blue and
      were surrounded by clear halos. Aspirated material collected in the syringe was
      cultured, and Cryptococcus neoformans was isolated. CONCLUSION: This case report
      suggests that a combination of FNAC and culture is a simple and useful method of
      diagnosing fungal infections. Early diagnosis by FNAC makes possible the early
      initiation of treatment.

PMID- 11284312
TI  - Fine needle aspiration cytology of foreign bodies presenting as cystic abdominal
      masses. A report of three cases.
AB  - BACKGROUND: Foreign body material (gauze sponges) presented as cystic abdominal
      masses and were confused with malignant tumors. CASES: Two females and one male
      presented with abdominal masses. They had undergone laparotomy 5-12 years
      earlier. Clinically the masses were diagnosed as benign or malignant cystic
      lesions. Fine needle aspiration revealed necrotic material, hemosiderin-laden
      macrophages, foreign body giant cells, cholesterol crystals and many fragments of
      birefringent material. The possibility of malignancy was ruled out. Cut sections
      of the excised cystic lesions revealed gauze sponges surrounded by a thick,
      fibrotic wall. CONCLUSION: This report underscores the usefulness of fine needle
      aspiration in ruling out malignancy.

PMID- 11284313
TI  - Aspiration biopsy of osseous metastasis of retroperitoneal paraganglioma. Report
      of a case with cytologic features and differential diagnostic considerations.
AB  - BACKGROUND: Paragangliomas are uncommon tumors, only 10% of which are malignant,
      as evidenced by metastatic disease. It is rare for paraganglioma to present with
      symptomatic osseous metastases. CASE: A retroperitoneal paraganglioma presented
      in a 52-year-old man as painful metastases in the rib and vertebrae. Fine needle
      aspiration (FNA) of a lumbar vertebral lesion showed cells arranged singly and in
      loose clusters with fragile, vacuolated or finely granular cytoplasm, marked
      anisonucleosis and mitoses. Rare zellballen-type structures and intranuclear
      inclusions were present. Immunohistochemical studies of a subsequent FNA core
      biopsy of the retroperitoneal mass showed strong immunoreactivity with
      chromogranin and negative staining for keratin; that was helpful in
      differentiating this tumor from others in the differential diagnosis. CONCLUSION:
      The cytologic diagnosis of paraganglioma is difficult as these tumors exhibit a
      plethora of features that overlap those of many other neoplasms. The diagnosis
      can be confirmed with appropriate immunohistochemical studies of corresponding
      core biopsies.

PMID- 11284314
TI  - Chondrosarcoma of the proximal femur with myxoid degeneration mistaken for
      chondromyxoid fibroma in a young adult. A case report.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) is effective in the diagnosis
      of bone tumors when combined with careful radiologic and clinical evaluation.
      However, cases where clinical or radiologic findings are atypical or unusual may
      lead to an erroneous diagnosis. CASE: A 19-year-old male presented with a pain in
      the left hip area that had been slowly progressive over a 10-month period.
      Clinical and radiologic findings suggested either giant cell tumor or
      chondroblastoma. The smeared aspiration specimen showed loosely cohesive, oval to
      round cells with moderate amounts of pale pink cytoplasm admixed with pinkish
      blue, chondromyxoid material. The individual cells contained a single nucleus
      with evenly distributed, fine chromatin. A few osteoclastic giant cells were
      scattered in the smears. A cytologic diagnosis of myxoid lesion with a few giant
      cells, suspicious for chondromyxoid fibroma, was made. The diagnosis of
      chondrosarcoma was made by subsequent histologic examination. CONCLUSION: Absence
      of the usual clinicoradiologic features of chondrosarcoma combined with an
      unusual cytologic presentation in this case led to a misdiagnosis. In most
      centers, FNAC has achieved undisputed status as a diagnostic tool, and cytologic
      diagnosis often forms the basis of the therapeutic protocol. However, at some
      sites FNAC diagnosis is more problematic. Awareness of the limitations and
      pitfalls of FNAC is just as important as knowledge of the scope of FNAC in bone
      tumors. Tumors with chondromyxoid features provide particular difficulties.

PMID- 11284315
TI  - Fine needle aspiration of toxoplasmic lymphadenitis in an intramammary lymph
      node. A case report.
AB  - BACKGROUND: Cytologic findings of toxoplasmic lymphadenitis (TL) have been only
      sporadically reported. Intramammary lymph node is an extremely rare site for TL.
      CASE: A 47-year-old, healthy, female presented with a breast tumor, which was
      aspirated. The cytomorphologic features were interpreted as suggestive of TL.
      Histopathology of the excisional biopsy specimen and subsequent serologic
      examination confirmed the diagnosis. CONCLUSION: We obtained several
      characteristic findings in aspiration of TL. Of these, epithelioid cell clusters
      and monocytoid cells were the most diagnostic.

PMID- 11284316
TI  - Fine needle aspiration cytology diagnosis of a cutaneous granular cell tumor in a
      7-year-old child. A case report.
AB  - BACKGROUND: Granular cell tumors are neoplasms of uncertain histogenesis,
      although a neural origin is favored. Most reports on the cytologic features of
      granular cell tumors have been on lesions from the breast or respiratory tract.
      However, there are only a few reports on fine needle aspiration (FNA) cytologic
      diagnosis of cutaneous or soft tissue granular cell tumors. CASE: A 7-year-old
      girl presented with a skin lesion on her right forearm of one year's duration.
      The FNA smears showed sheets and clusters of oval to polygonal cells with an
      abundant amount of granular cytoplasm. Many single, scattered cells with similar
      morphology were seen in the background. Immunostaining for S-100 protein showed
      granular cytoplasmic positivity. The tumor was diagnosed as a benign granular
      cell tumor. The histopathology report on the excised lesion confirmed the FNA
      diagnosis. CONCLUSION: The cytopathologic features of granular cell tumors
      presenting as skin lesions are distinctive enough to allow a correct diagnosis on
      FNA cytology.

PMID- 11284317
TI  - Cytologic features of pulmonary hamartoma. Report of a case diagnosed by fine
      needle aspiration cytology.
AB  - BACKGROUND: Pulmonary hamartoma (PH) is the most common benign tumor of the lung.
      It is usually composed of cartilage, fat, smooth muscle and respiratory
      epithelium. Its diagnosis is based on imaging methods (radiography, computed
      tomography) and cytohistomorphologic study by means of fine needle aspiration
      cytology (FNAC). CASE: A 59-year-old female had a productive cough and lung mass
      on chest radiography. Fine needle aspiration of the nodule showed a fusiform
      tumor cell, which was diagnosed as consistent with PH. The patient underwent
      surgery for the tumor. Histopathologic study confirmed the diagnosis of PH.
      CONCLUSION: The fluoroscopically guided FNAC specimen was adequate in achieving a
      diagnosis. Cytologic features consisted of a serosanguineous background in which
      scant cellular elements of spindle and stellate cells, as well as fibromyxoid
      material, enabled us to make a definitive diagnosis. Since this technique is
      relatively noninvasive, it is very useful in diagnosing PH before a preoperative
      biopsy.

PMID- 11284318
TI  - Epithelioid sarcoma. Report of a case with fine needle aspiration diagnosis.
AB  - BACKGROUND: Epithelioid sarcoma is a rare type of soft tissue sarcoma affecting
      the extremities, particularly the hands and fingers. Though it is well described
      histopathologically, publications regarding its cytologic findings are limited.
      CASE: A 52-year-old woman presented with swelling of the left middle finger. Fine
      needle aspiration was performed. Smears showed oval to polygonal cells with
      epithelioid features. A diagnosis of soft tissue sarcoma with a possibility of
      epithelioid sarcoma was suggested. Histopathologic examination and
      immunohistochemistry confirmed the diagnosis. CONCLUSION: In the presence of
      classic cytologic findings, the diagnosis of epithelioid sarcoma can be
      suggested. Subsequent histologic examination and immunohistochemistry can confirm
      the diagnosis.

PMID- 11284319
TI  - Disseminated cryptococcosis mimicking metastatic carcinoma: diagnosis by fine
      needle aspiration cytology.

PMID- 11284320
TI  - Giardia lamblia presenting as a right iliac fossa mass.

PMID- 11284321
TI  - Basement membrane substance in adenomyoepithelioma of the breast.

PMID- 11284322
TI  - Melanin pigment in aspirates from epidermal cysts.

PMID- 11284323
TI  - Periurethral vaginal melanoma: urine cytologic findings.

PMID- 11284324
TI  - Carbon paste-based electrochemical detectors for microchip capillary
      electrophoresis/electrochemistry.
AB  - The first reported use of a carbon paste electrochemical detector for microchip
      capillary electrophoresis (CE) is described. Poly(dimethylsiloxane) (PDMS)-based
      microchip CE devices were constructed by reversibly sealing a PDMS layer
      containing separation and injection channels to a separate PDMS layer that
      contained carbon paste working electrodes. End-channel amperometric detection
      with a single electrode was used to detect amino acids derivatized with
      naphthalene dicarboxaldehyde. Two electrodes were placed in series for dual
      electrode detection. This approach was demonstrated for the detection of
      copper(II) peptide complexes. A major advantage of carbon paste is that catalysts
      can be easily incorporated into the electrode. Carbon paste that was chemically
      modified with cobalt phthalocyanine was used for the detection of thiols
      following a CE separation. These devices illustrate the potential for an easily
      constructed microchip CE system with a carbon-based detector that exhibits
      adjustable selectivity.

PMID- 11284325
TI  - Capillary electrophoresis system with flow injection sample introduction and
      chemiluminescence detection on a chip platform.
AB  - A capillary electrophoresis (CE) system with chemiluminescence (CL) detection was
      combined with flow injection (FI) sample introduction on a chip platform. A
      falling-drop interface was applied to perform FI split-flow sample introduction
      while achieving electrical isolation from the CE high voltage. A tubular
      reservoir at the capillary outlet served as both the CL reaction and detection
      cell for the luminol-peroxide-metallic ion chemiluminescent reaction, with the
      luminol included in the separation buffer and CL reagent H2O2 continuously
      introduced into the outlet reservoir. An optical fiber was positioned within the
      outlet reservoir directly opposite, and 300 microns away from, the capillary
      outlet for collecting and transferring the generated CL to the PMT. The peak
      height signals and the separation efficiency were almost independent of the
      reagent flow-rate, making the system a robust one. The performance of the system
      was illustrated by the separation of Co(II) and Cu(II), achieving baseline
      separation in 60 s. Detection limits (3 sigma) were 1.25 x 10(-8) and 2.3 x 10(
      6) mol dm-3 for Co(II) and Cu(II), respectively. Peak height precision was 1.9%
      RSD (n = 9) at the 10(-7) mol dm-3 Co level.

PMID- 11284326
TI  - Investigations of the origins of estrogenic A-ring aromatic steroids in UK sewage
      treatment works effluents.
AB  - The present preliminary study describes an investigation of a putative
      aromatisation pathway in sewage from cholesterol through the corresponding A-ring
      aromatic steroid, norcholest-1,3,5(10)-trienol (NCT) to estrone. The synthesis
      and analytical characterisation of NCT and of the trimethyl silyl ether by gas
      chromatography-mass spectrometry, is described. The analytical properties of
      synthetic NCT were used to direct a search for the compound over several months
      in 1998 in the effluents of two sewage treatment works (STW; Deephams and
      Harpenden, north London). The study was prompted by the earlier findings that
      increased vitellogenin concentrations in the plasma of caged male rainbow trout
      held in the STW effluents (so-called fish 'feminisation') could be attributed to
      the presence of A-ring steroids such as estrone. Until now it has been assumed
      that these steroids originate from the STW influents and it is not clear to what
      extent, if at all, aromatisation of steroids might occur during STW operation.
      NCT was only detected in the solid particles associated with the effluents on one
      occasion in 8 months. This suggests that the hypothesised pathway is not a major
      one. Confirmation of previous reports of estrone and 17 beta-estradiol was also
      obtained using a published analytical method and by a simple modification of the
      method these reports were extended to include a regular occurrence of the weaker
      estrogen, 16 alpha-estriol in the case of Harpenden STW effluents in 1998.

PMID- 11284327
TI  - Liquid chromatography with post-column electrochemical treatment and mass
      spectrometric detection of non-polar compounds.
AB  - The first hyphenation of high performance liquid chromatography (HPLC),
      electrochemical online oxidation and mass spectrometry (MS) is described.
      Ferrocenecarboxylic acid esters of various alcohols and phenols have been
      synthesized, separated by reversed-phase HPLC and oxidized (ionized)
      coulometrically prior to single quadrupole MS analysis using electrospray
      ionization (ESI) and atmospheric pressure chemical ionization (APCI) interfaces.
      The dependence of the ionization on the electrochemical pretreatment is
      demonstrated. Limits of detection for selected derivatives range from 4 x 10(-9)
      to 4 x 10(-7) mol dm-3 depending on the individual compound and the selected
      interface.

PMID- 11284328
TI  - Micro sequential injection: fermentation monitoring of ammonia, glycerol,
      glucose, and free iron using the novel lab-on-valve system.
AB  - Using an integrated lab-on-valve manifold in a microfluidic sequential injection
      format (microSI), automated sample processing has been developed for off-line and
      on-line monitoring of small-scale fermentations. Spectrophotometric assays of
      ammonia, glucose, glycerol, and free iron were downscaled to use micro-quantities
      of commercial reagents. By monitoring the reaction rate, the response curves in a
      stopped-flow mode generate linear calibration curves for ammonia [r2 = 1.000
      (0.9% SE)], glycerol [r2 = 0.999 (1.1% SE)], glucose [r2 = 0.999 (1.1% SE)], and
      free iron [r2 = 0.999 (1.5% SE)]. Since sample dilution and reagent quantities
      are easily adjusted within the programmable SI format, the lab-on-valve system
      can accommodate samples over a wide concentration range (ammonia: 3-1200 ppm;
      glycerol: 20-120 ppm; glucose: 35-1000 ppm; and free iron: 80-400 ppm). This work
      demonstrates the key advantages of miniaturization through the reduction of
      sample and reagent use, minimizing waste and providing a compact yet reliable
      instrument. The lab-on-valve manifold uses a universal hardware configuration for
      all analyses, only requiring changes in software protocol and choice of reagents.
      All of these features are of particular importance to small-scale experimental
      fermentation where multiple analyte analyses are needed in real-time using small
      sample volumes. It is hoped that this first real-life application of the lab-on
      valve manifold will serve not only as a model system to downscale assays in a
      practical fashion, but will also inspire and promote the use of the integrated
      microSI manifold approach for a wider range of biotechnological applications.

PMID- 11284329
TI  - Study of the separation and determination of monosaccharides in soluble coffee by
      capillary zone electrophoresis with electrochemical detection.
AB  - A simple, fast and reliable method, based on capillary electrophoresis with
      electrochemical detection, for the separation and determination of six
      monosaccharides, namely glucose, galactose, arabinose, fructose, xylose and
      ribose, in soluble coffees was developed. A copper disk electrode was used as the
      working electrode. The optimum conditions for separation and detection were 50
      mmol L-1 sodium hydroxide buffer (pH 12.7), separation voltage 5 kV and detection
      potential 0.65 V (vs. Ag/AgCl). The linear ranges were from 5.0 x 10(-3) to 0.5
      mmol L-1 for all six sugars. All regression coefficients were > 0.99. The
      detection limits for all the sugars were 1.0 x 10(-3) mmol L-1. The RSD of the
      peak current was < 4.2% (n = 5). The proposed method was applied directly to the
      separation and determination of the six sugars without prior derivatization, and
      the assay results were satisfactory.

PMID- 11284330
TI  - Development of a capillary electrophoresis-77 K luminescence detection system for
      online spectral identification.
AB  - We have demonstrated that capillary electrophoresis (CE) can be easily interfaced
      with 77 K luminescence spectroscopy (LS) for separation and online spectral
      identification of structurally similar analytes. This novel CE-LS apparatus
      consists of a regular CE system, instrumentation for LS and a specially designed
      capillary Dewar. When the separating molecules traverse into the cryostat
      detection window, liquid nitrogen is added, freezing the separating analyte zones
      within the capillary. At low temperature, detection limits are improved via
      signal averaging and the inherent increase in quantum yield at 77 K. We present
      the first application of the CE-LS system to structural isomers (2,3- and 3,4
      methylenedioxymethamphetamine) and stereoisomers (trans- and cis-resveratrol).
      With this approach, the CE-LS interfacing provides a sensitive, accurate, rapid,
      simple and economic methodology for analytical chemistry.

PMID- 11284331
TI  - N-isobutyloxycarbonylation for improved detection of 3'-hydroxystanozolol and its
      17-epimer in doping control.
AB  - An improved screening method was developed for 3'-hydroxystanozolol and its 17
      epimer in human urine involving gas chromatography-mass spectrometry (GC-MS) with
      N-isobutyloxycarbonyl (isoBOC) and O-trimethylsilyl (TMS) derivatization. A
      procedure was reported previously for the pentane extraction of many steroids
      from urine in doping control, but it was not suitable for the detection of
      stanozolol metabolites. Compared with the n-pentane extraction method, which gave
      a poor recovery (< 10%), isoBOC extraction resulted in a good recovery (> 80%).
      The sensitivity and specificity of mixed N-isoBOC-O-TMS derivatization were
      adequate for the detection of 3'-hydroxystanozolol and its 17-epimer when 3 ml of
      urine was used with spiking at a level of 2 ng ml-1. When applied to a stanozolol
      positive urine sample, the proposed method allowed rapid and sensitive screening
      for the detection of 3'-hydroxystanozolol and its 17-epimer.

PMID- 11284332
TI  - Development of an analytical technique and stability evaluation of 143 C3-C12
      volatile organic compounds in Summa canisters by gas chromatography-mass
      spectrometry.
AB  - A technique using Summa canisters with cryogenic preconcentration and gas
      chromatographic-mass spectrometric (GC-MS) detection was developed to determine
      143 C3-C12 volatile organic compounds (VOCs) including alkanes, alkenes,
      aromatics and halohydrocarbons in ambient and indoor air. The method detection
      limits and practical quantification limits were sensitive at 0.02 and 0.10 ppbv,
      respectively, and the method precision and accuracy were also satisfactory. The
      stability of C3-C12 VOC standards at ppbv levels under elevated pressure in
      canisters was assessed over various time intervals (from 1 week to 4 months after
      preparation) and most of the compounds were found to be acceptably stable with a
      mean recovery of 85.6 +/- 9.9% during the course of a 4-month study. However, a
      small fraction (approximately 6%) of the compounds, including two
      halohydrocarbons (bromotrichloromethane and benzyl chloride) and six alkenes (2
      methylbuta-1,3-diene (isoprene), cis-4-methylpent-2-ene, cis-3-methylpent-2-ene,
      hept-1-ene, oct-1-ene and styrene) displayed relatively low recoveries in the
      range 34.6-67.9%. The loss of these compounds is most probably caused by their
      physical adherence to the active sites of the canister surface, chemical
      decomposition and/or reactions with other species. The results indicated that one
      must be cautious in attempting to measure these compounds owing to their
      instability in canisters. Overall, this analytical technique, which has been used
      for the determination of the VOCs under study in the toxic air pollutant
      monitoring network administered by the HKSAR Government, was amenable to the
      measurement of airborne VOCs collected both outside and inside a semi-confined
      car park in the present study.

PMID- 11284333
TI  - Simplified method for the determination of Ru, Pd, Re, Os, Ir and Pt in
      chromitites and other geological materials by isotope dilution ICP-MS and acid
      digestion.
AB  - A method for the determination of low Ru, Pd, Re, Os, Ir and Pt abundances in
      geological reference materials by isotope dilution inductively coupled plasma
      mass spectrometry (ICP-MS) after acid digestion in a high pressure asher (HPA-S)
      is presented. The digestion technique is similar to that using Carius tubes but
      easier to handle and reaches higher temperatures. Osmium can be determined as
      OsO4 with ICP-MS directly after digestion through a sparging technique. The
      remaining elements are preconcentrated by means of anion column chromatography.
      The resin is digested directly without elution leading to high yields but this
      causes problems if Zr is present at higher levels in the silicate rich materials.
      The analytical results for international platinum group element (PGE) reference
      materials, chromitite CHR-Bkg, basalt TDB-1 and gabbro WGB-1, are presented and
      compared with literature data, demonstrating the validity of the described
      method. Although higher in concentration, PGEs determined for reference material
      WGB-1 were worse than for TDB-1 indicating a more inhomogeneous distribution of
      the platinum group mineral phases. The low PGE abundance chromitite standard, CHR
      Bkg, is likely to be homogeneous for Ru, Re, Os and Ir and is recommended as a
      reference material for the study of chromitites. Detection limits (3s x total
      procedure blank) range from 0.012 ng (Re and Os) to 0.77 ng (Pt), which could be
      further improved by applying higher quality acids.

PMID- 11284334
TI  - Assessment of the fifth ligand-binding repeat (LR5) of the LDL receptor as an
      analytical reagent for LDL binding.
AB  - The fifth ligand binding repeat (LR5) of the low density lipoprotein (LDL)
      receptor was assessed ex vivo as an 'analytical reagent' to distinguish LDL
      state, in atherosclerosis risk monitoring. LR5 was immobilized to
      mercaptoundecanoic acid modified gold surfaces via a glycine linker. Surface
      plasmon resonance (SPR) was used to monitor LDL binding. Unfolded LR5 was
      ineffectual as an affinity ligand for LDL but refolded LR5 showed a high affinity
      for native LDL but little affinity for oxidized LDL. LR5 refolded in the presence
      of calcium or EDTA gave the equivalent LDL binding capacity. However, EDTA-LR5
      was less stable than Ca-LR5 at pH 5 and, from tryptophan fluorescence evidence,
      they appeared to involve different regions of LR5 and/or LDL in the binding.
      Involvement of amino acid residues of the calcium cage of LR5 was tested in LDL
      binding by monitoring calcium ion release with a calcium ionophore. The results
      were consistent with approximately 7-8 LR5 binding per LDL, of which only some
      induce calcium release (a maximum of approximately 25 mol% calcium, based on LR5,
      was released during LDL binding). For LDL binding to the LDL receptor in vivo
      more than one ligand-binding repeat is needed and this may be consistent with LR5
      acting here also at binding sites which other LRs normally occupy in the LDL-LDL
      receptor complex. This initial study is encouraging for the use of a minimum
      peptide repeat array based on the conserved region of the LRs as an affinity
      surface for atherosclerosis risk monitoring.

PMID- 11284335
TI  - Small volume bead assay for ovalbumin with electrochemical detection.
AB  - A bead based sandwich enzyme immunoassay coupled to electrochemical detection for
      ovalbumin has been developed. The enzyme label alkaline phosphatase was used to
      convert the substrate 4-aminophenyl phosphate to electroactive product 4
      aminophenol. The detection was done in a microdrop by continuously monitoring the
      enzyme turnover with a rotating disk electrode. This reduces dilution of the
      enzyme product, a key to achieving low detection limits. The assay developed has
      a detection limit of 0.1 ng ml-1. Assay sensitivity in complex matrices such as
      food and serum was compared.

PMID- 11284336
TI  - Blood platelet adhesion to protein studied by on-line acoustic wave sensor.
AB  - The attachment of blood platelets to the surface of bare and protein-coated
      thickness-shear mode acoustic wave devices operating in a flow-through
      configuration has been studied. Platelets in washed from bind to the gold
      electrodes of such sensors, but the resulting frequency shifts are far less than
      predicted by the conventional mass-based model of device operation. Adherence to
      albumin and various types of collagen can be produced by on-line introduction of
      protein or by a pre-coating strategy. Differences in attachment of platelets to
      collagen types I and IV and the Horm variety can be detected. Platelets attached
      to collagen yield an interesting delayed, but reversible signal on exposure to a
      flowing medium of low pH. Scanning electron microscopy of sensor surfaces at
      various time points in this experiment reveals that originally intact platelets
      are eventually destroyed by the high acidity of the medium. The reversible
      frequency is attributed to the presence of removable platelet granular components
      at the sensor-liquid interface.

PMID- 11284337
TI  - Picric acid sensitive optode based on a fluorescence carrier covalently bound to
      membrane.
AB  - An acryloyl group was attached to fluorescein through the phenol hydroxyl group
      to make it photopolymerizable with 2-hydroxypropyl methacrylate and covalently
      immobilized on an optode glass surface modified with gamma
      (methacryloxy)propyltrimethoxysilane. The optode system with a plastic-clad fused
      silica bifurcated fiber optic bundle shows satisfactory analytical performance
      characteristics for determining picric acid in terms of selectivity and
      reproducibility with a linear range from 8.0 x 10(-7) to 4.0 x 10(-3) mol L-1.
      The quenching mechanism was investigated. The optode membrane can be applied to
      the indirect determination of cinchonine drug and the results obtained were
      satisfactory.

PMID- 11284338
TI  - Electroanalytical exploitation of quinone-thiol interactions: application to the
      selective determination of cysteine.
AB  - Square wave voltammetry was applied to the detection of cysteine through the use
      of an indirect assay that exploits the reaction of the thiol with a quinone
      indicator. Voltammetric discrimination between unreacted quinone and the
      corresponding quinone-cysteine adduct is possible with clear resolution of the
      latter peak providing a linear response from 5 to 47 microM. The selectivity of
      the approach was assessed with no interference from cystine, lysine, paracetamol
      or 4-aminophenol. The response recorded in the presence of a massive excess of
      ascorbic acid was also investigated and the integrity of the approach confirmed.
      The effects of other sulfhydryl thiols, homocysteine and glutathione, were also
      assessed and found to present no appreciable change in the voltammetric profile.
      The practical utility of the approach was investigated through examining the
      response to cysteine in urine.

PMID- 11284339
TI  - Electrochemical determination of dopamine using a poly(2-picolinic acid) modified
      glassy carbon electrode.
AB  - A poly(2-picolinic acid) chemically modified electrode (CME) for the
      determination of dopamine (DA) by cyclic voltammetry is described. Compared with
      a bare glassy carbon electrode, the CME exhibits a 200 mV shift of the oxidation
      potential of DA in the cathodic direction and a marked enhancement of the current
      response. In pH 7.0 buffer solution, a linear calibration graph is obtained over
      the range from 2.5 x 10(-7) to 1.0 x 10(-5) mol dm-3 with a correlation
      coefficient of 0.998. The detection limit is 3.0 x 10(-8) mol dm-3. The modified
      electrode eliminated efficiently the interference from ascorbic acid (AA) when
      present in a 150-fold concentration ratio. It also showed excellent stability and
      reproducibility.

PMID- 11284340
TI  - Electrochemical studies and differential pulse polarographic analysis of
      lansoprazole in pharmaceuticals.
AB  - The electrochemical reduction of lansoprazole was investigated by cyclic
      voltammetry and direct current and differential pulse polarography. The reduction
      potential was -1.32 V vs. Ag/AgCl with a dropping mercury electrode in a
      supporting electrolyte consisting of phosphate buffer (pH 9.0)
      tetramethylammonium iodide (4 + 1). The reversibility of the electrode reaction
      and the type of limiting current were studied. The temperature coefficient and
      the diffusion constant were determined. A mechanism for the electrode reaction
      was proposed. A new simple and sensitive differential pulse polarographic method
      was also developed for the quantification of lansoprazole. A linear calibration
      graph was obtained in the range 0.04-11.35 micrograms ml-1. The limit of
      detection was 0.03 microgram ml-1 and the intra- and inter-day precisions were
      0.84-2.32 and 0.72-3.09%, respectively. The developed method was applied to six
      different commercial pharmaceutical capsule preparations containing enteric
      coated granules. The relative standard deviations ranged from 1.36 to 2.85%.
      Recovery studies for the accuracy of the method were performed by adding a
      synthetic mixture to known amounts of lansoprazole and the mean recovery was
      100.45%. The data obtained from commercial preparations were compared with those
      from a published spectrophotometric method. No difference was found
      statistically.

PMID- 11284341
TI  - Covalent modification of glassy carbon electrode with glutamic acid for
      simultaneous determination of uric acid and ascorbic acid.
AB  - A novel covalently modified glassy carbon electrode with glutamic acid has been
      fabricated via an electrochemical oxidation procedure and was applied to the
      catalytic oxidation of uric acid (UA) and ascorbic acid (AA), reducing the
      overpotentials by about 0.2 V and 0.3 V, respectively. Based on its strong
      catalytic function toward the oxidation of UA and AA, the modified electrode
      resolved the overlapping voltammetric response of UA and AA into two well-defined
      voltammetric peaks with both cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV), which can be used for the simultaneous determination of these
      species in a mixture. The catalytic peak current obtained from DPV was linearly
      dependent on the UA and AA concentration in the range 2 x 10(-6)-4 x 10(-4) mol L
      1 and 1.0 x 10(-6)-4 x 10(-4) mol L-1 with correlation coefficients of 0.996 and
      0.997, respectively. The detection limits (3 delta) for UA and AA were 1.1 x 10(
      6) mol L-1 and 9.2 x 10(-7) mol L-1, respectively. The modified electrode shows
      good sensitivity, selectivity and stability, and has been applied to the
      determination of UA and AA simultaneously in human urine samples with
      satisfactory results.

PMID- 11284342
TI  - Implementation of a chemical equilibrium constraint in the multivariate curve
      resolution of voltammograms from systems with successive metal complexes.
AB  - A multivariate curve resolution (MCR) method, using a constrained alternating
      least squares (ALS) procedure with a new chemical equilibrium constraint, was
      applied to differential-pulse polarograms of successive metal complexes. This new
      restriction imposes the fulfillment of a chemical model defined by a set of
      stability constants that are optimised along the iterative ALS procedure. The
      reliability of the method was tested with simulated data and with polarograms
      measured for the systems Zn(II) + glutathione and Cd(II) + 1,10-phenanthroline.
      These systems respectively yield two and three successive and electroactive
      complexes, which are inert from the electrochemical point of view, that is, the
      complexes virtually do not dissociate during the measurement. Although the
      presence of electrode adsorption could induce overestimation of some
      concentrations and losses of linearity between concentrations and signals, the
      results showed that the proposed method can yield satisfactory estimations of the
      stability constants in this kind of system. The performance of the new method is
      compared with the performances obtained using MCR-ALS without the equilibrium
      constraint and using traditional curve fitting least-squares approaches.

PMID- 11284343
TI  - Determination of physical properties of bitumens by use of near-infrared
      spectroscopy with neural networks. Joint modelling of linear and non-linear
      parameters.
AB  - The fact that bitumens behave as non-Newtonian fluids results in non-linear
      relationships between their near-infrared (NIR) spectra and the physico-chemical
      properties that define their consistency (viz. penetration and viscosity).
      Determining such properties using linear calibration techniques [e.g. partial
      least-squares regression (PLSR)] entails the previous transformation of the
      original variables by use of non-linear functions and employing the transformed
      variables to construct the models. Other properties of bitumens such as density
      and composition exhibit linear relationships with their NIR spectra. Artificial
      neural networks (ANNs) enable modelling of systems with a non-linear property
      spectrum relationship; also, they allow one to determine several properties of a
      sample with a single model, so they are effective alternatives to linear
      calibration methods. In this work, the ability of ANNs simultaneously to
      determine both linear and non-linear parameters for bitumens without the need
      previously to transform the original variables was assessed. Based on the
      results, ANNs allow the simultaneous determination of several linear and non
      linear physical properties typical of bitumens.

PMID- 11284344
TI  - Mediaeval cantorals in the Valladolid Biblioteca: FT-Raman spectroscopic study.
AB  - Raman spectroscopic studies of three mediaeval cantorals in the Biblioteca of the
      University of Valladolid has revealed information about the pigments used on
      these large manuscripts. Although executed in a simple colour palette, very pure
      cinnabar was used as the major colourant, offsetting the carbon black of the
      verses and script. A dark blue colour was achieved using a mixture of azurite
      (basic copper carbonate) and carbon, whereas a light blue colour was azurite
      alone. A grey colour was achieved using azurite, carbon particles and a
      calcareous 'limewash'. A yellow pigment, used sparely in the cantorals was
      ascribed to saffron; unusually, there was no evidence for the presence of the
      yellow mineral pigments orpiment, realgar and massicot. In several regions of the
      vellum specimens, evidence for biodeterioration was observed through the
      signatures of hydrated calcium oxalate. We report for the first time the Raman
      spectra of pigment in situ on a vellum fragment, which also shows evidence of
      substrate bands; comparison of black and red pigmented regions of vellum
      specimens has shown the presence of calcium oxalate in the black pigmented script
      but not in the red pigment regions, which suggests that the cinnabar in the red
      pigmented regions acts as a toxic protectant for the vellum substrate against
      biological colonisation processes.

PMID- 11284345
TI  - An optimised single-reagent method for the speciation of chromium by flame atomic
      absorption spectrometry based on surfactant micelle-mediated methodology.
AB  - The toxicity of chromium in the environment is dependent on the species in which
      it exists. This paper outlines a method for the analysis of the oxidation states
      of Cr employing a suitable chelating agent and the cloud point phenomenon for
      Cr(VI) and total Cr analysis. The method involves preconcentration of metal
      chelates followed by air-acetylene flame atomic absorption spectrometric
      analysis. The chelating agent chosen for this task is the ammonium
      pyrrolidinedithiocarbamate, which reacts with either Cr(VI) or total Cr under
      specific experimental conditions. The condensed surfactant phase with the metal
      chelate(s) is introduced into a flame atomic absorption spectrometer, whereby
      discrimination of Cr species is feasible by calculating the Cr(III) concentration
      from the difference between total Cr and Cr(VI). A multivariate design was
      employed to study the variables affecting the overall analytical performance for
      total Cr assay. The analytical curves are rectilinear up to 100 micrograms l-1
      for both oxidation states of the metal. The limits of detection are 0.6 microgram
      l-1 and the relative standard deviation (n = 5) at a concentration of 30
      micrograms l-1 for both species is around 2.0%. The method was validated by
      analysing BCR 544 reference material certified for both Cr species. High
      recoveries in the range 96-107% were attained for the environmental and
      biological samples tested.

PMID- 11284346
TI  - Oscillatory control of sample dispersion in a continuous flow system.
AB  - A new strategy for the instrumental control of sample dispersion in continuous
      flow systems is presented. The method is based on shaking a loosely held straight
      reactor while the sample travels through the flow injection manifold. This
      external disturbance yields a sample transport more similar to the plug flow type
      because of the changes promoted on the flow pattern. Up to a three-fold increase
      in peak height, a comparable reduction in peak width and a more Gaussian peak
      profile are observed when the signals obtained with the shaken reactor are
      compared with those obtained with the same reactor but static. Improvements in
      the analytical performance as a function of different operational variables are
      shown for systems with or without a chemical reaction. Analytical implications
      and possible uses are discussed since this strategy allows the control of
      dispersion by simply selecting the frequency and amplitude of oscillation.

PMID- 11284347
TI  - Determination of 226Ra in biological samples by adsorption on specific adsorbers.
AB  - The determination of 226Ra in biological samples, such as milk and grass, was
      studied. 226Ra analysis of cow's milk was studied starting from de-fatted milk.
      The proteins were eliminated by coagulation of the colloidal phase with
      trichloroacetic acid. Phosphorus was then removed by precipitating it as
      molybdophosphate and finally adsorption was carried out by using two different
      adsorbers in order to concentrate and purify radium. Lead rhodizonate (LEHRO)
      adsorbed on charcoal and partially reduced tin dioxide (PRTD) were utilised. A
      method for the determination of 226Ra in grass ashes was also investigated. The
      main interference, due to magnesium, hinders the use of LERHO, so the proposed
      procedure is based on adsorption of radium on PRTD at pH 9.5. The magnesium
      concentration was depleted by precipitating barium (carrier) and radium with
      calcium carbonate at pH 8 before the adsorption step. The high phosphorus
      concentration in grass also interferes in the determination of 226Ra; phosphorus
      was eliminated as above via molybdophosphate precipitation. The radium was
      carried by barium and spiked with 133Ba. The yield of the chemical procedure was
      evaluated on the basis of 133Ba activity. Radium samples were alpha-counted and
      the activity was evaluated with a suitable calibration curve. Both exchangers in
      the milk analysis and PRTD in grass analysis were shown to be helpful in order to
      set up an easily performed procedure, which allows many samples to be processed
      simultaneously. All the methods adopted were shown to be very sensitive. Under
      the experimental conditions used, with 1 L of milk or 5 g of grass ashes, the
      limit was about 3 mBq 226Ra L-1 milk and < 1 mBq 226Ra g-1 grass ashes.

PMID- 11284348
TI  - Analysis of fuel oxygenates in the environment.

PMID- 11284349
TI  - [Multiple trauma with craniocerebral trauma].

PMID- 11284350
TI  - [Multiple trauma with craniocerebral trauma. Early definitive surgical management
      of long bone fractures?].
AB  - Head injuries are found in 17.6% of all trauma in-patients and are the most
      common cause of death after injury (26.6%) in Germany. Main factors for the
      initial and follow up assessment are the Glasgow Coma Scale (GCS) and pupil
      reaction. These are of a very predictive value for the outcome and are essential
      for the emergency crew to choose the adequat trauma hospital. Secondary transport
      to a higher level trauma center is affected by additional risk factors and a
      delay in diagnosis resp. treatment. This will increase mortality and must be
      strictly avoided. Sufficient oxygenation and circulation prevent the patient from
      secondary brain damage. A low GCS (< or = 8 p.) or specific additional injuries
      are an indication for immediate intubation. The outcome in patients with a
      systolic blood pressure below 90 mmHg on arrival is worse: The longer the time of
      correction the lower the rate of survival. After resuscitation early fracture
      treatment depends on hemoglobin concentration, hemostasis, oxygenation, body
      temperature, injury pattern and on the initial cranial CT scan. Cerebral
      swelling, seen or expected, is a contraindication for definitive fracture
      stabilization. After resuscitation reassessment should be done including a second
      CT scan. Cerebral monitoring is best performed by continuous measuring of the
      intracranial and the arterial pressure. Their difference determines the cerebral
      perfusion pressure which should be 60 mmHg at least. Intracranial pressure rates
      below 20 mmHg are favourable. Optimal management within the first days is
      essential for good outcome.

PMID- 11284351
TI  - [Problems of malunited fractures of the distal radius].
AB  - The essential problematic of the distal fracture of the radius lies in the
      quality of its reduction and retention. 35 patients with distal fractures of the
      radius and strain fractures of the styloid process of the ulna were followed up
      with regard to their functional and radiological results and their subjective
      symptoms. Patients with intra-articular fractures were found to have
      significantly poorer functional results compared to those with extra-articular
      fractures. 29 out of 35 patients developed a nonunion of the styloid process of
      the ulna in the form of a compensatory false position with a significant dorsal
      tilt of the articular surface of the radius. Their functional results were also
      significantly poorer than those of the other 6 patients. The patients whose radii
      were shortened by more than 2 mm also had significantly poorer functional results
      and a median dorsal tilt of 5 degrees of the articular surface. Where the dorsal
      inclination of the articular surface of the radius exceeded 5 degrees, a
      significant increase in the scapholunar angle, which averaged 62 degrees, was
      found. On the basis of these figures, we conclude that in the reduction of the
      distal fracture of the radius, shortening by not more than 2 mm and a dorsal
      inclination of the articular surface of the radius, taken laterally, of not more
      than 5 degrees should be tolerated in order to minimise functional impairments of
      the wrist.

PMID- 11284352
TI  - [Navigation assisted by image conversion. An experimental study on pelvic screw
      fixation].
AB  - Within an experimental trial the new method of fluoroscopy based navigation was
      tested for percutaneous pelvic screw fixations. A regular C-arm was used and the
      navigation system developed by Medivision. In a first step appropriate C-arm
      projections were defined for five standardized screw positions. Then precision
      and fluoroscopy time of 60 screws in 6 artificial pelves were evaluated. For the
      sacroliacal screw in S1, S1 screw in S2, anterior column screw, posterior column
      screw and the supraacetabular ilium screw three to four appropriate projections
      were defined. These were all combinations of the known special pelvic views
      inlet/outlet and iliac/obturator. Using these standardized views the average
      fluoroscopy time was 6 seconds per screw. 51 screws (85%) were inserted
      correctly. In five cases there was a slight deviation without perforating the
      cortex, four times the cortex was perforated.

PMID- 11284353
TI  - [Madreporic hydroxyapatite granulates for filling bone defects].
AB  - Two macrocrystalline madreporic granular hydroxyapatite implants of different
      size range (single crystal size within both implants 1-3 microns) were implanted
      for 7, 28, 84 and 168 days into the trabecular bone of the distal femur epiphysis
      of rabbits. Both materials were investigated histologically. For testing of
      granular materials a new animal model has been developed. The drill hole was
      closed by reimplantation of an autologeous chondrocortical tissue slice to
      prevent loss of particles into the knee-joint. Both of the granular materials
      tested developed increasing bone bonding from the 7th day on to outer surfaces
      and pore surfaces. The degradation of both of the materials affected the
      superficial implant layers in soft-tissue interfaces exclusively and was mainly
      due to passive processes, e.g. leaching, fragmentation of granules after crack
      production, particulate degradation and subsequent phagocytosis of liberated
      implant particles by macrophages and foreign body giant cells. Zones of
      superficial implant degradation were bonded partially to bone a second time. A
      possible low-degree, active superficial degradation by foreign body giant cells
      is discussed. Osteoclasts of typical morphology as being observed on other
      hydroxyapatite implant surfaces were not demonstrated. This was related to the
      low degradation rate of the implants. Both of the granular materials tested are
      useful in filling bone defects. A guided tissue regeneration due to partial
      implant degradation and subsequent bone formation seems to be impossible since
      the degradation rate of the materials is too low.

PMID- 11284355
TI  - [Ambulatory prevention of thrombosis in traumatology].
AB  - There are no guidelines for the use of heparin in the prophylaxis of deep vein
      thrombosis in outpatients. In a prospective clinical investigation in 1996 and
      1997, 1321 outpatients after trauma of the lower extremities were screened by
      duplex-color-coded-ultrasound in order to detect deep vein thrombosis. There were
      two separate groups: group A with drug prophylaxis of deep vein thrombosis (n =
      723) and group B (n = 598) without. The classification A or B was mainly related
      to the ability of weight bearing (at least 20 kp) and of ankle mobility (at least
      20 degrees). Patients who did not achieve both criteria were classified in group
      A and were treated with heparin until they attained a higher level of activity
      (B). Group A showed 30 deep vein thrombosis while group B had no thromboembolic
      complications. We conclude that outpatients achieving a level of activity close
      to a physiological situation will show no thromboembolic complications.

PMID- 11284354
TI  - [Predicting the outcome in severe injuries: an analysis of 2069 patients from the
      trauma register of the German Society of Traumatology (DGU)].
AB  - On hospital admission numerous variables are documented from multiple trauma
      patients. The value of these variables to predict outcome are discussed
      controversially. The aim was the ability to initially determine the probability
      of death of multiple trauma patients. Thus, a multivariate probability model was
      developed based on data obtained from the trauma registry of the Deutsche
      Gesellschaft fur Unfallchirurgie (DGU). PATIENTS AND METHODS: On hospital
      admission the DGU trauma registry collects more than 30 variables prospectively.
      In the first step of analysis those variables were selected, that were assumed to
      be clinical predictors for outcome from literature. In a second step a univariate
      analysis of these variables was performed. For all primary variables with
      univariate significance in outcome prediction a multivariate logistic regression
      was performed in the third step and a multivariate prognostic model was
      developed. RESULTS: 2069 patients from 20 hospitals were prospectively included
      in the trauma registry from 01.01.1993-31.12.1997 (age 39 +/- 19 years; 70.0%
      males; ISS 22 +/- 13; 18.6% lethality). From more than 30 initially documented
      variables, the age, the GCS, the ISS, the base excess (BE) and the prothrombin
      time were the most important prognostic factors to predict the probability of
      death (P(death)). The following prognostic model was developed: P(death) = 1/1 +
      e(-[k + beta 1(age) + beta 2(GCS) + beta 3(ISS) + beta 4(BE) + beta 5(prothrombin
      time)]) where: k = -0.1551, beta 1 = 0.0438 with p < 0.0001, beta 2 = -0.2067
      with p < 0.0001, beta 3 = 0.0252 with p = 0.0071, beta 4 = -0.0840 with p <
      0.0001 and beta 5 = -0.0359 with p < 0.0001. Each of the five variables
      contributed significantly to the multifactorial model. CONCLUSIONS: These data
      show that the age, GCS, ISS, base excess and prothrombin time are potentially
      important predictors to initially identify multiple trauma patients with a high
      risk of lethality. With the base excess and prothrombin time value, as only
      variables of this multifactorial model that can be therapeutically influenced, it
      might be possible to better guide early and aggressive therapy.

PMID- 11284356
TI  - [Good Clinical Practice. Importance in clinical research].

PMID- 11284357
TI  - [Manubriosternal dislocation caused by indirect flexion-compression trauma. A
      case report and review of the literature].
AB  - Manubriosternal dislocation caused by indirect flexion-compression trauma is an
      extremely rare condition. Two forms of manubriosternal luxation are
      distinguished: in type I the sternum is dislocated posterior and in type II
      anterior to the manubrium. Direct or indirect trauma may cause manubriosternal
      dislocation. Mode of injury in direct trauma is mostly a head-on collition in a
      motor accident resulting either in type I or type II luxation. The unusual origin
      of manubriosternal dislocation by indirect trauma is put down to flexion
      compression injuries of the thoracic spine and results in a type II dislocation.
      Predisposition to manubriosternal dislocation by indirect trauma consists in
      rheumatoid arthritis or extreme forms of kyphosis. Outcome of many patients
      treated conservatively after initial reposition with adhesive tape, symptomatic
      pain therapy, cryotherapy and prohibition of any physical training over several
      weeks is subluxation or complete luxation of the manubriosternal joint. This
      condition may lead to chronic pain, periarticular calcification with ankylosis
      and progredient deformation. Lacking a controlled study for treatment of
      manubriosternal dislocation a standard therapeutic regime could not be
      established yet. In the literature only a few case-reports of patients undergoing
      operative therapy are published. We report a type II dislocation of the
      manubriosternal joint caused by indirect flexion-compression trauma. We achieved
      a very good long-term result using a 8-hole 1/3 tubular plate for fixation of the
      manubriosternal joint after reposition.

PMID- 11284358
TI  - [Correction of the leg axis after epiphyseal fracture and progressive abnormal
      growth of the proximal tibia].
AB  - Development of an angular deformity around the knee joint, following a
      posttraumatic premature epiphyseal closure is a rare but serious complication. We
      present a case report of this complication following a proximal tibial epiphyseal
      injury in a 9 year old child initially treated conservatively with plaster
      immobilization. Subsequently, partial closure of epiphysis on medial side
      resulted in genu varum of 20 degrees, which was treated with medial open wedge
      osteotomy of the proximal tibia combined with resection of a segment from the
      proximal fibula, and a percutaneous epiphysiodesis of the proximal tibia and
      fibula. At three years follow up, the child had shortening of the leg by 1 cm,
      but no angular deformity. Significance of regular follow-up after an epiphyseal
      injury to detect the condition and role of operative management with various
      modalities is discussed.

PMID- 11284359
TI  - [Atraumatic locked posterior-inferior shoulder luxation in a child].
AB  - We report a rare case of recurrent atraumatic posterior-inferior dislocation of
      the shoulder in an eight year old girl. After closed reduction of the locked
      dislocation and conservative treatment three further dislocations occurred.
      Because of the recurrence of locked dislocations and functional impairment
      arthroscopy including partial synovectomy was performed. Postoperative
      rehabilitation included the use of a brace in handshake position for six weeks
      and strengthening exercises. Within a clinical followup of 24 months the shoulder
      remained stable without loss of function but atraumatic posterior-inferior
      dislocation of the contralateral shoulder occured. The bilateral involvement
      indicates a predisposing factor, predominantly gross capsular laxity, of this
      rare form of instability.

PMID- 11284360
TI  - [Quality management in surgery: how do I convert guidelines in the clinical
      practice?].

PMID- 11284361
TI  - Statin therapy--what now?
AB  - In England, only 30% of patients with established coronary heart disease (CHD)
      and raised serum lipids, and fewer than 4% of individuals eligible for primary
      prevention, receive lipid-lowering therapy. Target total cholesterol
      concentrations are achieved in fewer than 50% of patients who do receive such
      treatment. Here, we review the use of statin therapy in the prevention of CHD
      events.

PMID- 11284362
TI  - Lifestyle measures to tackle atherosclerotic disease.
AB  - Epidemiological studies show that lifestyle, including diet, affects risk for
      coronary heart disease (CHD) and stroke. Here, we discuss how lifestyle changes
      can improve outlook in high-risk individuals, that is, people who have clinically
      obvious atherosclerotic disease, or those who are at significant risk of
      developing the problem.

PMID- 11284364
TI  - [Reabsorption syndrome after transurethral resection (TUR) of the prostate:
      review of physiologic, diagnostic, and therapeutic features].
AB  - In spite of the development of non-invasive strategies, surgical treatment of the
      prostate (TURP) and, mostly transurethral resection, is the most effective choice
      for patients suffering from benign prostatic hyperplasia who do not respond
      properly to pharmacological treatment. Absorption of hypotonic fluids used during
      TURP may cause hemodynamic and central nervous system disturbances. These
      symptoms, both taken separately or as a whole, are best known as "Transurethral
      prostatic resection syndrome" or "TURP syndrome". The original description of
      this syndrome dates from half a century ago; however, a number of items regarding
      its physiopathology and treatment remain unclear. We present a review of this
      pathological entity, compiling diagnostic and therapeutical approaches.

PMID- 11284365
TI  - [The first 20 years of history in Actas Urologicas Espanolas (1977-1996)].

PMID- 11284366
TI  - [DNA ploidy determination with flow cytometry, Ki-67 index and overexpression of
      p53 protein in 121 T1 superficial bladder carcinomas. Retrospective studies. Part
      II: Prognostic value and usefulness in the indication for prophylactic treatment
      with BCG].
AB  - OBJECTIVE: Evaluate the utility of Ki-67 label index, p53 expression and flow
      cytometry-DNA ploidy in the selection of groups to be treated with prophylactic
      BCG and the prognostic value compared with the classic variables (grade,
      lymphatic permeation, multiplicity, volume, primary). MATERIAL & METHOD: 121
      superficial bladder tumors T1. 10% Cut-off level for Ki-67 and p53. Aneuplody is
      defined as a tumor with DNA index different of 1 or more than 20% in G2-M phase.
      71 (58.7%) received BCG. RESULTS: In uni and multivariate analysis positivity to
      Ki-67 is correlated with recurrence. Progression is correlated with lymphatic
      permeation (p .0003), volume (p .016), ploidy (p .022) and positivity to p53 (p
      .007). In multivariate analysis, volume and positivity to p53 are independent
      variables. None were of utility to prevent recurrence, but Ki-67 positive or
      aneuploid treated tumors had less progression (p .025 and p .009 respectively).
      The p53 negative treated tumors had less progression too. CONCLUSIONS: Only Ki-67
      is correlated with tumoral recurrence. P53 and tumor volume are correlated with
      stage progression. If the results are confirmed with bigger series, the Ki-67
      positive and/or aneuploid tumors would obtain benefits of prophylactic treatment
      with BCG.

PMID- 11284367
TI  - [Adverse effects of transrectal prostatic biopsy. Analysis of 303 procedures].
AB  - INTRODUCTION AND OBJECTIVE: Prostate biopsy is a basic step towards prostate
      cancer (Pca) diagnosis, but usually not free from complications. In this article
      we have reviewed the adverse effects of this procedure in our setting. MATERIAL
      AND METHODS: We studied in a prospective fashion the complications arising from
      transrectal prostate biopsy with the aid of a questionnaire fulfilled by 303
      patients who underwent this procedure, within the context of a Pca screening
      program. All biopsies were transrectal ultrasound guided and randomly taken
      (sextant). A cleaning enema was applied the night before, and 100 mg of
      intramuscular tobramycin were administered prior of the procedure. RESULTS:
      Ninety patients (29.7%) had no adverse effects at all, and 136 (44.9%) reported
      at least one minor complication (hematuria, hemospermia, or autolimited dysuria).
      Lastly 77 (25.4%) presented with major complications--urinary retention, fever,
      need for medical assistance (primary or hospital care) or treatment. Thirty-five
      patients (11.5%) reported to present with fever after biopsy, 145 (47.8%)
      hematuria, 95 (31.3%) hemospermia, 77 (25.4%) rectal bleeding, 67 (22.1%) urinary
      difficulty, and 9 (2.9%) urinary retention. Up to 39 (12.8%) needed to visit
      their G.P., and 19 of them were referred to Hospital, where only 6 (1.9%) were
      admitted longer than 24 hours. No intensive care unit admittances or deaths were
      reported. CONCLUSIONS: The rate of post-transrectal biopsy adverse effects is
      high in our experience. This phenomenon could be explained, in part, due to data
      collecting by means of a self-administered questionnaire. Probably the high fever
      rate presented here could be diminished with other type of antibiotic
      prophylaxis.

PMID- 11284368
TI  - [Treatment of lithiasis in horseshoe kidney with extracorporeal shock-wave
      lithotripsy].
AB  - The horseshoe kidney is the most frequent renal anomaly. As a consequence of
      impaired urinary drainage, urolithiasis is present in 20% of the cases.
      Indications for extracorporeal shock wave lithotripsy (ESWL) in the treatment of
      patients with anomalous kidneys is still the subject of controversy. OBJECTIVE:
      To evaluate ESWL efficacy in the treatment for lithiasis in horseshoe kidney.
      MATERIAL AND METHODS: Between april 1988 and december 1999 a total of 32
      symptomatic lithiasis in 30 patients with horseshoe kidneys were managed by 65
      sessions with ESWL. Until march 1999 a Dornier HM-4 electrohydraulic lithotripter
      was used. Posteriorly, two treatments was performed with an electromagnetic
      Dornier Lithotripter S. These procedures have been performed without anaesthesia
      or sedation for the Dornier HM-4 equipment. Analgesia with Meperidine was used
      for the Dornier Lithotripter S. Diuresis was not forced during or after treatment
      with diuretics or serotherapy. Treatments was conducted in an outpatient clinic
      in all cases. RESULTS: Treatment/lithiasis rate was 2.03. Following treatment 16
      patients (54%) were stone-free by X-ray, 9 patients (30%) had residual fragments
      and in 5 patients (16%) no sign of stone disintegration was observed. Open
      surgery was performed in three of this patients. Better results was achieved in
      stones located in the renal pelvis and stone size is 10 mm or less. Clinical
      evolution: free of symptoms in 20 patients; chronic vague flank pain in 5
      patients and acute renal colic with or without hematuria in 5 patients. No major
      complication was observed in our compilation. CONCLUSIONS: These results suggest
      that ESWL is the method of primary choice in the treatment for small lithiasis
      (10 mm or less) in horseshoe kidney.

PMID- 11284369
TI  - [Ureteral complications of retroperitoneal prosthetic vascular surgery].
AB  - OBJECTIVE: Ureteral obstruction following retroperitoneal vascular by-pass has
      rarely been reported in the international world literature (only 169 cases).
      That's why we present three new cases to contribute at best knowledge of this
      iatrogenic disease. MATERIAL AND METHOD: Our cases were diagnosed by symptoms
      (number 2 and 3) and incidentally (number 1). The case 3 is exceptional because
      only 6 cases were previously described. RESULTS: Three different treatments were
      applied in our cases. The urinary fistula resulted into nephrectomy and the
      others were treated by endourological and reconstructive methods. We noted that
      the added comorbidity factors in all these cases make the pronogstic hazardous.

PMID- 11284370
TI  - [Is it necessary to use an isotopic diuretic renogram in grade II pyelocaliceal
      dilatations diagnosed with ultrasonography?].
AB  - PURPOSE: The increasing number of ultrasonographically detected asymptomatic,
      renal dilations have caused a lot of explorations to be performed in these
      patients. The Society of Fetal Urology proposed a four grades classification of
      echographic renal dilations and renographic studies are recommended in grades II
      to IV. However we have observed that grade II dilations don't evolve to
      obstruction. The aim of this work is to evaluate the obstruction rate in this
      group of patients, and the necessity or not of practising diuretic renography.
      MATERIAL AND METHODS: We studied 42 children diagnosed of grade II renal dilation
      during a 1.5 year period. Left side was more frequently affected, 23 cases, 7
      cases were bilateral what means 49 affected renal units. There was a male
      predominance (69%). Mean age at diagnosis was 2 months (0 to 36 months). Seventy
      nine per cent were prenatally diagnosed. RESULTS: The MAG-3 renal scan showed 48
      unobstructed renal units and 1 obstructed. The F-15 variant was made in 15 cases
      by a doubtful curve or retarded elimination. The patient with obstructive curve
      presented an 15 mm renal pelvic diameter echographically measured and the
      intravenous urography showed a higher dilation being operating on. The mean time
      follow up was 23.5 months (13 to 53 months) without any change. CONCLUSION: Grade
      II pielocalicial dilations with renal pelvis lesser than 15 mm can be
      echographically controlled without renal scan. It should be performed only if
      renal dilation increases.

PMID- 11284371
TI  - [Selective embolization of post-traumatic renal pseudoaneurysm in monorenal
      patient].
AB  - Presentation of one case of a patient who presented two non-penetrating abdominal
      traumatism along a year period. In the first incident it was necessary to
      practice a left nefrectomy and in the second one the therapeutic opcion was a
      superselective embolization of a pseudoameurism communicated with urinary tract.

PMID- 11284372
TI  - [Pneumocysts, unusual infective complication in diabetics].
AB  - We report on a case of fully gas-filled bladder with no evidence of intramural
      gas, fistula between bladder and gastrointestinal tract or instrumentation. The
      patient is diagnosed of a diabetic neurogenic bladder. We comment the causes of
      this rare finding and its relation with emphysematous cystitis.

PMID- 11284373
TI  - [Kluyvera ascorbata. Case report of a patient with Crohn's disease].
AB  - For the not frequent, we contributed a new case of infection urinary produced by
      the I generate Kluyvera. We make a bibliographical review, clinical expression of
      the same and we insisted in a series of peculiarities, you like the appearance
      give because of the treatment pharmacologic and their intestinals.

PMID- 11284374
TI  - [Squamous carcinoma of the prostate].
AB  - A primary squamous cell carcinoma occurring in the prostate of 84 year-old man is
      described. The patient died of local progression six months after diagnosis.
      Review of the literature suggests that such a cancer of the prostate is rare,
      highly aggressive, and responds poorly to any mode of therapy.

PMID- 11284375
TI  - [Sertoli cell tumor of the testis].
AB  - Sertoli cell tumors (TCS) derivated from sex-cord estroma cells, are an uncommon
      variety of testicles neoplasms. A 66 year-old patient that came to the
      consultation for an increased scrotum of size present. Ultrasound viewed a
      hipoecoic nodule capable with testicular tumor, more secondary hidrocele. After
      undergoing the standard treatment, by means of groin radical orchiectomy, its
      pathologic analysis identified the lesion as Sertoli cell tumor conventional. The
      pathologic features that best correlate with a clinically benign course are as
      follows: a lower size tumor to 5 cm, mild nuclear atypia, a mitotic rate of less
      than 5 mitosis per 10 high power fields, and absent necrosis. Our case presented
      with these features. Follow-up of these neoplasms should be prolonged by the
      unusual of its presentation and a small percentage of cases are clinically
      malignant.

PMID- 11284376
TI  - [Prostatic angiosarcoma: report of a new case].
AB  - We report the case of a 31 year old male, with lower urinary tract symptoms. We
      achieved the diagnosis of an prostate angiosarcoma. The treatment was a
      retropubic radical prostatectomy and partially resection of bladder neck,
      followed by chemotherapy with Ifosfamide and Adriamycin. At least 36 months up to
      surgery the patient is alive and free of symptoms and radiological signs of
      recurrence.

PMID- 11284377
TI  - [Large renal leiomyoma].
AB  - Renal leiomyomas are uncommon between renal tumors, and they have a benign
      mesenchymatous origin. Because of their low incidence, unspecific symptomatology
      an not well-defined iconographic semiology, they often raise problems with
      differential diagnosis from kidney masses, although they are often big size
      lessions. We report a patients with incidentally diagnosis of big solid left
      renal mass, who underwent radical nephrectomy resulting kidney pelvis leiomyoma.
      Diagnostic, histological and therapeutic aspects are briefly review in
      literature. Emphasis is made on the relevance of a high index suspicion
      considering big solid asymptomatic renal masses in middle-age women. Specially in
      renal tumors with well-defined limits and abscence of locoregional and systemic
      dissemination. We emphasized usefulness of Magnetic Angioresonance,
      immunohystochemical test and conservative surgery opportunity in small renal
      leiomyomas preoperatively confirmed.

PMID- 11284378
TI  - Direct-to-consumer promotion of prescription drugs. Economic implications for
      patients, payers and providers.
AB  - Spending on outpatient prescription drugs in the US is accelerating rapidly.
      Although numerous factors are driving this trend, attention has recently focused
      on the role played by the marketing, promotion and advertising of
      pharmaceuticals, in particular direct-to-consumer (DTC) advertising. In 1997, the
      US Food and Drug Administration (FDA) issued a 'guidance' on such mass media
      promotion. The guidance altered existing FDA rules and effectively permitted
      pharmaceutical companies to promote prescription drugs on television and radio
      without giving detailed or even summary information on indications, efficacy or
      potential adverse effects. Since then, television commercials, in particular, and
      print advertisements in consumer magazines and newspapers have proliferated
      rapidly. Pharmaceutical companies spent $US1.8 billion on DTC advertising in
      1999, a 40% increase over 1998. This spending in 1999 was heavily concentrated on
      about 50 drugs. Evidence is growing that DTC promotion of prescription drugs is:
      (i) alerting consumers to the existence of new drugs and the conditions they
      treat; (ii) increasing consumer demand for many drugs; (iii) contributing
      increasingly to the recent sharp increase in the number of prescriptions being
      dispensed; (iv) raising sales revenues; and, thus, (v) contributing to the higher
      pharmaceutical costs of health insurers, government and consumers. The public
      policy issues surrounding DTC advertisements centre on the following questions:
      (i) are the advertisements leading to the inappropriate clinical use of some
      drugs? (ii) are the advertisements inducing both consumers and physicians to
      choose more costly new brand-name drugs over less expensive, but equally
      effective, older brand or generic drugs? (iii) do television advertisements for
      prescription drugs contain a balanced amount of information on benefits versus
      potential adverse effects? and (iv) will the revenue benefits generated by DTC
      advertising cause pharmaceutical companies to focus more on developing products
      to treat prevalent but not life-threatening conditions, such as baldness, sexual
      dysfunction or memory loss? These questions are just beginning to be probed
      despite prescription drug spending, insurance coverage and payment policies
      having become major political issues in the US.

PMID- 11284379
TI  - Quality-of-life assessment in comparative therapeutic trials and causal structure
      considerations in peripheral occlusive arterial disease.
AB  - When considering the use of quality of life as a primary end-point in phase III
      to IV comparative trials, the trial designer generally faces some unresolved
      questions. These include: How does one explain that some dimensions [quality-of
      life (QOL) instruments usually have more than 1 dimension] are directly
      influenced by the studied treatments whereas others are not? How can one
      interpret conflicting results between conventional clinical measurements and QOL
      measurements, when the relationships between conventional clinical measurement
      and quality of life are not known? In this paper, we consider the use of
      Structural Equation Modelling (SEM) as a methodological alternative to answer
      these problems. As an example, we analyse the internal causal structure of the
      Claudication Scale (CLAU-S), a specific QOL 5-dimensional instrument for
      peripheral occlusive arterial disease. In applying SEM to different studies and
      different types of calculation, we suggest that CLAU-S is based on a stable,
      simple and comprehensive QOL model, is compatible with the general International
      Classification of Impairments, Disabilities and Handicaps (ICIDH) classification,
      is coherent and complementary with clinical data measurements and, using
      differences in a prospective study, considerably improves specificity. We suggest
      that SEM can help in QOL scale validation, in providing a unified scheme of the
      inter-relationships between internal dimensions and with external variables, in
      particular, clinical measurements.

PMID- 11284382
TI  - Health-related quality of life (HR-QOL) and regulatory issues. An assessment of
      the European Agency for the Evaluation of Medicinal Products (EMEA)
      recommendations on the use of HR-QOL measures in drug approval.
AB  - Interest in measuring qualitative aspects of life that are most closely related
      to health and healthcare has increased in recent years. Methods of describing
      patients' subjective health status now incorporate standardised measures, and
      several psychometric measures are available. Despite the thousands of empirical
      and conceptual papers in the medical and pharmacological literature on health
      related quality of life (HR-QOL), the value of such measures in the regulatory
      process is still being debated. We conducted an assessment to understand and
      document the position of the European Agency for the Evaluation of Medicinal
      Products (EMEA) on the use of HR-QOL measures in studies conducted for regulatory
      purposes. Official documents produced and circulated by the EMEA containing
      recommendations on trial design, conduct and analysis for sponsors and scientific
      experts were independently reviewed by authors to document the position of the
      Agency on the specific topic of HR-QOL. All documents found in the Agency website
      on 30 September 1999 were identified and then assessed to: (i) identify diseases
      or drugs for which formal HR-QOL assessment is recommended; (ii) identify
      measures and methods recommended; and (iii) evaluate the reliability of
      recommendations across documents. Of the 189 documents retrieved, none focused
      directly on health-related quality of life. A few explicit recommendations were
      identified for 13 specific drugs or conditions. These recommendations were mostly
      general and vague, and used nonstandard terminology. In addition, terminology and
      recommendations were not consistent across documents and, in at least one case,
      were in contrast with the US Food and Drug Administration (FDA) guidelines. EMEA
      guidelines incorporating quality-of-life outcomes are welcomed but it is obvious
      that more detailed guidance is required. Closer collaboration between the EMEA
      and the FDA is also recommended. Experts from different disciplines should be
      involved in the preparation of such documents to assure the necessary technical
      expertise and the representativeness of the various counterparts.

PMID- 11284383
TI  - The multinational impact of migraine symptoms on healthcare utilisation and work
      loss.
AB  - OBJECTIVE: To compare self-reported healthcare resource utilisation, paid work
      loss, unpaid work loss and loss of effectiveness at work due to migraine in a
      clinic-based adult migraine population. METHODS: The Migraine Background
      Questionnaire (MBQ) was translated and pilot-tested for use in 25 countries. The
      questionnaire was then self-administered by patients at a screening visit for 3
      phase III clinical trials of rizatriptan [a selective serotonin (5
      hydroxytryptamine) 5-HT1B/1D receptor agonist] in 23 US and 78 non-US sites.
      PARTICIPANTS: Persons 18 to 65 years of age with at least a 6-month history of
      moderate to severe migraines prior to the screening visit were surveyed. RESULTS:
      A total of 2670 persons (54.7% Europe, 16.5% Latin America, 23.1% North America,
      5.5% other countries) completed the MBQ and had responses which could be
      analysed. On average, each patient reported 2.78 doctor visits, 0.53 emergency
      room visits and 0.06 hospitalisations related to migraine per year. Patients self
      reported being only 46% effective while on the job with migraine symptoms.
      Extrapolation of patient self-reported work and productivity loss for the last 4
      weeks to an annual basis suggested that clinic-based patients with migraine lose
      19.5 workday equivalents (8.3 days due to absenteeism, 11.2 days due to reduced
      workday equivalents) due to migraine per year. In the US, the annual employer
      cost of this total migraine-related work loss is estimated to be $US3309 (2000
      values) per patient with migraine. The levels of self-reported healthcare
      resources utilised for migraine and work loss were generally consistent across
      geographic regions. CONCLUSIONS: The impact of migraine symptoms on healthcare
      resource utilisation and work loss was similar across most measures in Europe,
      Latin America, North America and other countries. Total migraine-related work
      loss due to absenteeism and reduced workday equivalents accounts for most of the
      economic burden of migraine, regardless of country, in a clinic-based migraine
      population.

PMID- 11284381
TI  - A review of health-related quality-of-life measures in stroke.
AB  - The objective of this review was to evaluate health-related quality of life (HR
      QOL) measures for use with patients with stroke. HR-QOL measures are increasingly
      used for assessment in many health conditions; these measures may serve an
      important role in evaluating the impact of stroke and of stroke interventions. HR
      QOL measures used in patients with stroke should: (i) cover the domains of HR-QOL
      that may be affected by stroke; (ii) have administration characteristics suitable
      for use in patients with stroke; and (iii) have undergone reliability and
      validity assessment in patients with stroke. The present study evaluates HR-QOL
      measures with reference to these requirements. A systematic literature review was
      conducted to identify and evaluate HR-QOL measures of potential use in studies of
      patients with stroke. Identified measures were assessed with regard to stroke
      relevant domains covered, measure characteristics (e.g. self-administration
      versus administration by an interviewer, interviewer time to complete) and
      psychometric properties of reliability and validity. The measures evaluated vary
      widely on domains covered, and limited assessment of the performance of HR-QOL
      measures has been conducted in patients with stroke. No existing measure
      comprehensively covers all relevant domains or addresses fully the issues of
      obtaining and combining HR-QOL assessments in patients and proxies in many stroke
      populations. Additional psychometric testing in stroke populations is needed for
      existing HR-QOL measures. In addition, stroke-targeted HR-QOL measures need to be
      developed and evaluated with patients with stroke.

PMID- 11284380
TI  - Changing therapeutic regimens in benign prostatic hyperplasia. Clinical and
      economic considerations.
AB  - About one-quarter of men aged 50 years and older experience voiding problems due
      to benign prostatic hyperplasia (BPH). Until about 10 years ago, surgery
      (particularly transurethral resection of the prostate) was the only effective
      treatment for symptomatic BPH. Over the last decade, several new treatments have
      been introduced. These include different types of medication (alpha-blockers and
      finasteride), thermotherapy, laser prostatectomy, needle ablation and
      vaporisation methods. The diffusion of these less invasive treatment modalities
      has resulted not only in a decrease in the age-adjusted surgery rates, but also
      in an increase of the total number of men treated for BPH. A large number of
      studies on clinical benefits and risks reveal that the conventional types of
      surgery remain the most effective treatments, whereas new interventional
      therapies require a shorter hospital stay and result in fewer short term
      complications. The efficacy of medication is lower than that of interventional
      treatments. Adverse effects include dizziness and orthostatic hypotension (alpha
      blockers) and decreased sexual function (finasteride), but are generally mild.
      There is some evidence that medication and minimally invasive treatments may
      preclude eventual surgical treatment, but the precise effect is difficult to
      estimate because of differences in the study populations and the relatively short
      study periods. As a result of the dynamic nature of BPH treatment and the lack of
      long term data, the cost effects of the introduction of the various new
      treatments are also difficult to assess. Given the aging of the population and
      the growing percentage of patients with BPH for whom any type of treatment can be
      considered, a considerable increase of total costs can be expected. Long term
      prospective studies are necessary to gain insight into the most cost-effective
      treatment for different patient groups.

PMID- 11284384
TI  - Usefulness of US cost-of-illness studies in healthcare decision making.
AB  - OBJECTIVE: Cost-of-illness studies have been completed on scores of diseases over
      the past 30 years. The goal of this study was to review published cost-of-illness
      studies on US populations in order to evaluate the potential usefulness of the
      results in decision making. METHODS: Medline and related databases were searched
      using diagnosis and economic terms. The bibliographies of the articles found were
      reviewed visually to identify further studies. Inclusion criteria required a
      specified diagnosis, the study to be published between 1 January 1985 and 30
      April 1999 in an English-language peer-reviewed journal, a clearly defined US
      sample or national population, available and recent epidemiological data on
      prevalence and incidence of diagnosis, and money estimates of direct and/or
      indirect costs. Three readers reviewed each study. The senior reviewer settled
      all differences. RESULTS: Searches found 1725 published studies; only 110 (6.4%)
      met all inclusion criteria. Main reasons for rejection were insufficient cost
      data (80%), insufficient information on data sources and aggregation or
      estimation methods (56%), inadequate sector data e.g. hospitalisations or work
      loss (48%), study of value, not cost, of illness (44%), not a US population (30%)
      and insufficient population detail (19%). There were 80 diagnosis categories, 28
      of which had more than one study. Only 5 diagnoses had > or = 5 studies-
      Alzheimer's dementia, depression, diabetes mellitus, mental illness and stroke.
      Multifold cost variations were found among studies within diagnosis categories,
      even with the same method and data sources. The more narrowly defined diagnoses,
      depression and stroke, had the smallest cost variation, 41.7 and 17.2%,
      respectively. A generalised linear regression model found that a significant
      portion of total and direct cost variance could be explained only for Alzheimer's
      dementia. CONCLUSIONS: The wide variation of cost estimates for the same
      diagnosis raises serious questions of comparability, accuracy, validity and
      usefulness of all studies. Implementing guidelines to standardise methods and
      study design for cost-of-illness studies would be a worthwhile first step. The
      advantages and disadvantages of using money or another metric such as disability
      adjusted life-years as the prime outcome measure should also be publicly
      discussed.

PMID- 11284385
TI  - Cost-effectiveness analysis of pneumococcal vaccination for elderly individuals
      in The Netherlands.
AB  - OBJECTIVE: To assess the cost effectiveness (net costs per life year gained) of
      pneumococcal vaccination of elderly individuals aged 65 years and over in The
      Netherlands. DESIGN AND SETTING: A pharmacoeconomic analysis was conducted from
      the healthcare perspective in The Netherlands. The gender- and age-specific
      modelling framework linked epidemiological aspects of invasive pneumococcal
      disease (e.g. incidence, mortality, life years lost) to vaccination and hospital
      resource use. To derive 90% confidence limits for net costs per life year gained
      a stochastic analysis was performed. INTERVENTION: Pneumococcal vaccination in
      the elderly with the 23-valent vaccine. Effectiveness of the vaccine in
      preventing invasive pneumococcal disease was derived from international studies.
      MAIN OUTCOME MEASURES AND RESULTS: Pneumococcal vaccination in the elderly was
      not found to be cost saving. At baseline, stochastic and univariate sensitivity
      analysis net costs per life year gained were estimated to be between 6000 and
      16,000 euro (EUR) [EUR1 = 1.1 US dollars; cost level 1995]. A scenario analysis
      on alternative age-dependent vaccination strategies indicated even higher net
      costs per life year gained, up to EUR28,000 for vaccinating only those elderly
      aged 85 years and over. CONCLUSIONS: Pneumococcal vaccination is associated with
      net costs per life year gained of EUR10,100 (at baseline assumptions). These
      costs are higher than those for influenza vaccination (EUR5500). Our
      pharmacoeconomic approach, which needs to be considered in conjunction with
      social, psychological and budgetary issues, is intended to contribute to rational
      decision-making in healthcare policy.

PMID- 11284386
TI  - [Molecular techniques lead to the first insights into the pathophysiology of
      salivary gland adenomas].
AB  - Pleomorphic adenomas are the most common type of salivary gland tumours.
      Activation of the PLAG1 gene on chromosome 8q12 is the most frequent mutation
      found in these tumours. This results from chromosomal translocations leading to
      promoter substitution between PLAG1, mainly expressed in fetal tissue, and more
      broadly expressed genes. The replacement of the PLAG1 promoter, inactive in adult
      salivary glands, by a strong promoter derived from the translocation partner,
      leads to ectopic expression of PLAG1 in the tumor cells. This abnormal PLAG1
      expression results in deregulation of PLAG1 target genes causing salivary gland
      tumorigenesis. PLAG1 binds to promoter 3 of the Insulin-like growth factor 2 gene
      (IGF2) and stimulates its activity. IGF2 is highly expressed in salivary gland
      adenomas overexpressing PLAG1 while no IGF2 expression is found in adenoma
      without abnormal PLAG1 expression nor in normal salivary gland tissue, indicating
      a perfect correlation between PLAG1 and IGF2 expression. These results provide us
      with the first clue for understanding the role of PLAG1 in salivary gland tumor
      development. IGF2 perfectly fits in the picture of a restarted developmental
      program with concomitant loss of differentiation, the typical hallmark for any
      tumour. Salivary gland genesis provides a system for studying the development of
      glandular organs having many basic features in common with the salivary gland,
      such as breast, kidney, lung, pancreas and prostate. With a unique salivary gland
      organ culture system we now can study principles of epitheliogenesis,
      tubulogenesis and branching morphogenesis. Genes expressed at the spot where
      during tumourigenesis proliferation overrules differentiation constitute new
      targets for reverting the proliferative, tumour-specific stage. By elucidating
      molecular mechanisms involved in human cancer, we will hence contribute at the
      level of fundamental cancer research (oncogenesis) and normal organ development
      (organogenesis).

PMID- 11284387
TI  - Parasitic vaccines: an utopia or reality?
AB  - Major advances in biotechnology over the past decade have led to significant
      progress in antigen selection, recombinant protein production and antigen
      delivery in a number of host-parasite systems. Vaccination against complex
      metazoan parasites has become a reality with the development of recombinant
      vaccines against the cattle tick Boophilus microplus and the sheep cestode Taenia
      ovis. In the present paper progress towards the development of similar vaccines
      against other parasites is discussed, with gastrointestinal nematodes and
      schistosomes in ruminants as examples. Special emphasis is put on antigen
      selection strategies and on the practical requirements for successful
      vaccination.

PMID- 11284388
TI  - Peptide truncation by dipeptidyl peptidase IV: a new pathway for drug discovery?
AB  - Membrane peptidases are a group of ectoenzymes with a broad functional
      repertoire. In protein metabolism, their importance is well known, especially in
      peptide degradation and amino acid scavenging at the intestinal and renal brush
      border. However, they also perform more subtle tasks; not only do they provide or
      extinguish signals by cleaving exterior peptide mediators, but they also may
      function as receptors or participate in signal transduction or in adhesion.
      Dipeptidyl peptidase IV (DPPIV), which is identical to the lymphocyte surface
      glycoprotein CD26, is unique among these peptidases because of its ability to
      liberate Xaa-Pro and less efficiently Xaa-Ala dipeptides from the N-terminus of
      regulatory peptides. It occurs in the plasma membrane as a homodimer with a total
      molecular mass of 22-240 KdA and the C-terminal domain probably forms on
      alpha/beta hydrolase fold. In addition to, but independent of its serine type
      catalytic activity, DPPIV binds closely to the soluble extracellular enzyme
      adenosine deaminase. The in vivo expression on epithelial, endothelial and
      lymphoid cells of DPPIV is compatible with a role as physiological regulator of a
      number of peptides that serve as biochemical reporters between and within the
      immune and neuroendocrine system. Surprisingly, not cytokines with a N-terminal
      Xaa-Pro motif, but a number of chemokines have recently been identified as
      substrates. Despite DPPIV mediates only a minimal N-terminal truncation,
      important alterations in chemokine activities and receptor specificitIes were
      observed in vitro together with modified inflammatory and antiviral responses.
      Most probably the great flexibility of the N-terminus of a number of chemokines
      facilitates the accessibIlity to the catalytic site of DPPIV. Other known
      substrates which are subject in vitro to receptor-specific changes induced by
      DPPIV truncation include neuropeptides such as substance P, peptidE YY and
      neuropeptide Y. On the other hand, DPPIV mediated cleavage of the N-terminal His
      Ala or Tyr-Ala dipeptides from circulating incretin hormones like, glucagon-like
      peptides (GLP)-1 and -2, gastric inhibitory polypeptide (GIP), all members of the
      enteroglucagon/GRF superfamily, results in their biological inactivation in vitro
      and in vivo. Administration of specific DPPIV inhibitors closes this pathway of
      incretin degradation and greatly enhances insulin secretion. The improved glucose
      tolerance in several animal models for type II diabetes points to specific DPPIV
      inhibition as a pharmaceutical approach for type 2 diabetes drug development.

PMID- 11284389
TI  - A population-based study on the determinants of heart rate and heart rate
      variability in the frequency domain.
AB  - The main objective of the present study was to identify the determinants of heart
      rate (HR) and of the low-frequency (LF) and high-frequency (HF) components of
      short-term heart rate variability (HRV) in the population. HF power represents
      vagal modulation of HRV and LF power predominantly sympathetic modulation. Data
      were collected in a population-based sample of 614 men and women, aged 25-89
      years. Because of the uncertainty on the optimal methodology for power spectral
      analysis of HRV, we first compared the results obtained with the two most
      frequently used methods. We found that autoregressive modelling and fast Fourier
      transform yielded similar overall qualitative results, but that within subject
      differences between methods could be considerable. Results could also differ
      according to whether they were expressed in absolute (ms2) or in normalized (%)
      units. Age and gender significantly influenced HR and various components of HRV.
      Furthermore we observed significant interactions between age and gender regarding
      several components of HRV, indicating that men and women differ at younger age,
      but not after the age of about 50 yrs. Parasympathetic modulation appeared to be
      greater in women than in men at younger age, but not after the age of menopause.
      The changes of HR and HRV on standing were attenuated with increasing age.
      Influences of body mass index, smoking, alcohol consumption and habitual physical
      activity were small to negligible. In conclusion, the employed methodology and
      several demographic, anthropometric and/or lifestyle characteristics should be
      taken into account for the interpretation of HRV in cardiovascular disease.

PMID- 11284390
TI  - [Research and scientific progress in the year of 2000].

PMID- 11284391
TI  - [New diagnostic tools in pathological anatomy. The Danish Society of Pathologic
      Anatomy and Cytology].

PMID- 11284392
TI  - [Mammaplasties. The Danish registry of mammaplasties].

PMID- 11284393
TI  - [Emergency pediatric/monitoring department. The Danish Pediatric Society].

PMID- 11284394
TI  - [The urologic specialty. The Danish Society of Urology].

PMID- 11284395
TI  - [Treatment of apoplexy--a cooperation between neurologic and geriatric
      departments. The Danish Society og Geriatrics].

PMID- 11284396
TI  - [DanishLungCancer Registry. The Danish Society of Thoracic Surgery].

PMID- 11284397
TI  - [Current and near-future progress (and regress) within hepatology. The Danish
      Society of Hepatology].

PMID- 11284398
TI  - [Vascular surgery at the cross roads. The Danish Society of Vascular Surgery].

PMID- 11284399
TI  - [Computer aided surgery (CAS) and minimally invasive nasal/sinus surgery. The
      Danish Society of Otolaryngology, Head & Throat Surgery].

PMID- 11284400
TI  - [Infection medicine in the year of 2000. The Danish Society of Infection
      Medicine].

PMID- 11284401
TI  - [Investigation of malignant melanoma. The Danish Melanoma Group].

PMID- 11284402
TI  - [Anesthesiology and intensive medicine--a pannordic issue of concern. The Danish
      Society of Anesthesiology and Intensive Medicine].

PMID- 11284403
TI  - [Hip dysplasia. Treatment with osteotomy by means of Ganz. The Danish Orthopedic
      Society].

PMID- 11284404
TI  - [Functional neurosurgery and neuromodulation. The Danish Society of Neurosurgery
      and the Danish Society of Neurology].

PMID- 11284405
TI  - [PET tumor diagnosis with modified gamma camera: gamma PET. The Danish Society of
      Clinical Physiology and Nuclear Medicine].

PMID- 11284406
TI  - [Preimplantation diagnosis. The Danish Society of Obstetrics and Gynecology].

PMID- 11284407
TI  - [New therapies of chronic inflammatory bowel disease: anti-TNF antibodies and
      probiotics. The Danish Society of Gastroenterology].

PMID- 11284408
TI  - [What is happening within cancer drug therapy? The Danish Society of Medical
      Oncology].

PMID- 11284409
TI  - [Progress within psychiatric genetics and psychiatric epidemiology. The Danish
      Psychiatric Society].

PMID- 11284410
TI  - [Coronary bypass surgery without the use of heart-lung machine: status and
      perspectives. The Danish Society of Thoracic Surgery].

PMID- 11284411
TI  - [Genetic variation and disease of human beings. The Danish Society of Medical
      Genetics].

PMID- 11284412
TI  - [Unstable angina pectoris and non-Q-myocardial infarction. The Danish Society of
      Cardiology].

PMID- 11284413
TI  - [Activated protein C in severe sepsis--joyful news].

PMID- 11284414
TI  - [Prevention of instant restenosis after coronary angioplasty by implantation of
      rapamycin-coated stents].

PMID- 11284415
TI  - [A new aspect of clinical research conditions].

PMID- 11284416
TI  - [Albumin, evidence and meta-analysis: can the judgement be appealed?].

PMID- 11284417
TI  - [Honest nutritional counseling on vitamin E supplementation].

PMID- 11284419
TI  - [APO or not?].

PMID- 11284418
TI  - [Alcohol--risk factor in the development of type 2 diabetes?].

PMID- 11284420
TI  - [Effect of hormone replacement therapy on the cardiovascular system].
AB  - Hormonal replacement therapy becomes frequently used in peri- and postmenopausal
      women. It causally affects the climacteric syndrome, positively stimulates
      psychics, improves quality of the skin, decreases dryness of mucous membranes and
      frequency of recurrent inflammations of eyes and vagina. The positive influence
      on the bone metabolism and therefore on the incidence of osteoporosis highly
      dominates among its long-term effects. Long lasting hormonal replacement reduces
      also the incidence of Alzheimer disease, colorectal carcinoma and it has
      particularly favourable effect on the cardiovascular system. Estrogens positive
      affect the lipid spectrum, however, more than 50% of their beneficial influence
      comes from their direct vasodilatory effect. Estrogene replacement becomes in
      many countries indicated for the primary prevention of the ischemic heart
      disease. The question of its application for the secondary prevention remains
      still open.

PMID- 11284421
TI  - [Endocrinology 1999-2000].
AB  - Long-lasting problem on the differentiation of adenohypophyseal cell, which
      prepares them for their specific tasks (somatotropic, lactotropic ect.), becomes
      elucidated after recognition of the differentiational effect of transcription
      factor Pit-1. Expression of that factor in somatotrops results in STH secretion,
      contrary to lactotrops producing prolactin. Subclinical hypothyreosis (increased
      TSH with normal T3 and T4) endangers vessel not because of hypercholesterolemia,
      but because of changes in the dynamics of the blood flow. The idea of
      cardiotropic effect of thyroidal hormones is supported by the finding that
      administration of trijodthyronine to children after the surgical correction of
      heart malformations (cardiopulmonary bypass) improves myocardial function--it
      elevates cardiac output and decreases requirements on the intensive care.
      Receptors for hormones in tissues are flexible, they can be "heterooligomers" for
      dopamine and somatostatin. Mutations of mineralocorticoid receptor may cause
      hypertension in pregnancy and progesterone receptors have several isoforms.
      Receptors can be also activated by short exposition to a hormone. Glucocorticoids
      have probably also membrane receptors. Diabetes mellitus "type I" needn't to be
      immunogenic and DM type II not only results from down-regulation of receptors and
      subsequent insulin resistance, but it can be also caused by defects in insulin
      secretion. Insulin has receptors in the brain and participates in the appetite
      regulation. The attempt to use "desensibilisation" by peroraly administered
      insulin in patients with immunogenic DM had no effect. Stress affects memory
      mechanisms, heavy emotional stress during gravidity can bring congenital
      malformations. The decrease of mental functions in aged women depends on the
      level of free estradiol (the fraction, which is not bound to plasma proteins).
      Activation of dopaminergic neurons can be achieved by neurotropic growth factors.
      Nesiritide is a recombinant brain natriuretic hormone successfully tested in
      heart failure. The role of leptin in the appetite regulation in man is still not
      clear, other signalling molecules may have also an effect, e.g., ghrelin, which
      primarily stimulates STH secretion and brings about weight gain. Sildenafil
      influences nitrergic neurons elsewhere than in penis, for example it has positive
      effects in patients with oesophageal achalasia.

PMID- 11284422
TI  - [A method for modeling skin explants--an in vitro predictive test for graft vs
      host disease in allogenic hematopoietic cell transplantation].
AB  - BACKGROUND: Acute graft versus host disease (GvHD) remains a severe complication
      of allogeneic haematopoietic stem cell transplantation (HSCT). Our study
      summaries results of skin explant assay (SEA) as a pretransplant GvHD predictive
      test in a cohort of paediatric (n = 33) and adult (a = 8) patients receiving
      grafts from their HLA identical siblings (n = 28), haploidentical relatives (n =
      3) and unrelated donors (n = 10). Results GvHD prediction are correlated with the
      occurrence and severity of acute GvHD posttransplant and effect of GvHD
      prophylaxis on GvHD clinical outcome is evaluated. METHODS AND RESULTS: SEA
      utilises responding lymphocytes of the donor, which are sensitized firstly in
      vitro by mononuclears cells of patient in allogeneic mixed lymphocyte culture
      (MLC) and subsequently co-cultured with recipient's skin. Histopathological
      changes found in patients' skin explants are evaluated according to standard
      Lerner classification for acute GvHD. In general, GvHD predictive results in SEA
      correlated with GvHd clinical outcome in 28 out of 41 tested patients (68%, p =
      0.015). In a cohort of HLA identical sibling transplants GvHD predictive results
      correlated with clinical manifestation of acute GvHD only in 15 out of 28
      patients on individual GvHD prophylaxis. GvHD prophylaxis in the form of
      cyclosporine A (CsA) combined with short-term methotrexate (MTX) reduced the risk
      of acute GvHD in 10 out of 14 transplanted patients (71%) meanwhile CsA alone
      prophylaxis only in 1 out of 5 patients (20%). In a cohort of unrelated pairs on
      CsA/MTX prophylaxis combined with horse anti-lymphocyte globuline (ALG)
      correlated the GvHD prediction with GvHD clinical outcome (100%, p = 0.003). In
      all patients transplanted with the grafts from their haploidentical relatives the
      occurrence of severe GvHD was predicted. CONCLUSION: Skin explant assay helps
      identify pretransplant patients at higher risk of severe acute GvHD. GvHD
      predictive results enable the transplantation team to individualise GvHD
      prophylaxis and to optimise selection of the donor.

PMID- 11284423
TI  - [Polymorphisms in genes for cholesterol ester transfer protein, apolipoprotein C
      III and lipoprotein lipase in children with high and low cholesterol levels] ].
AB  - BACKGROUND: High plasma lipids are one of the risk factor of atherosclerosis. The
      contribution of environmental and genetic factors to plasma lipids is roughly
      equal. Cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL) and
      apolipoprotein (apo) CIII play an important role in plasma lipid metabolism. The
      aim of the study was to establish the role of polymorphisms in these genes in
      plasma lipid determination. METHODS AND RESULTS: Using PCR and restriction
      analysis we have measured Taq1 polymorphism in CETP, asparagine 291/serine
      polymorphism in LPL and C3238G polymorphism in apo CIII genes in two groups of
      children selected from opposite ends of the cholesterol distribution curve of
      2000 children. 82 children in high- (HCG) and 86 in low- (LCG) cholesterol group
      participated in the study. No significant difference was found in the frequencies
      of the CETP and apo CIII genotypes between LCG and HCG. In the LCG, significantly
      more carriers (p < 0.05) of the LPL serine291 allele were found. CONCLUSIONS:
      Common polymorphisms in the CETP and apo CIII genes do not determine the plasma
      lipid levels in childhood. The carriers of the rare allele in the LPL gene could
      be genetically predisposed to low plasma lipid levels.

PMID- 11284424
TI  - [Prevention of bacterial endocarditis in patients with prosthetic heart valves].
AB  - American Heart Association published in 1997 new version of recommendations for
      prevention of bacterial endocarditis in risk patients. Postoperative stadium in
      patients with prosthetic valve belongs to the highest risk. Infection can develop
      during bacteremia, which occurs most frequently at stomatologic and urologic
      interventions. The whole scale of medical interventions can be covered by two
      universal antibiotical regimes--one for the mouth, respiratory and upper GI
      tract, second for urogenital and lower GI tract. In the first case 2 g of
      Amoxicillin are administered p.o. 2 hours before the intervention. Interventions
      are individually listed, and cases where antibiotical prophylaxis is not
      recommended are separately given. Special situations are discussed.

PMID- 11284425
TI  - [The return of Czech health professionals to Most in the spring of 1945].
AB  - During the chaotic days of May 1945 the hospital--a crucial point of the health
      services in Most--was taken over in an orderly manner by Czech authorities. This
      was followed by gradual organizational steps leading to supplementation of the
      medical and nursing staff by Czech employees. The arrival of medical
      personalities was very important.

PMID- 11284426
TI  - [Hyperbaric oxygen therapy in non-healing wounds and defects] ].
AB  - Our study presents effects of the hyperbaric inhalation oxygenotherapy in the
      treatment of ischaemic diseases of lower extremities and chronic refractory
      problem wounds. Hyperbaric oxygenotherapy (HO) has antioedemic effect, it
      stimulates collagen synthesis, formation of granular tissue, and antimicrobial
      capacity of leukocytes. It also stimulates formation of new blood vessels, which
      is important namely in tissue hypoxia accompanying microangiopathy of the
      diabetic foot. HO should be administered as soon as possible after the diagnosis
      is fixed. Treatment should be done in co-operation with various specialists:
      surgeons, diabetologists, angiologists, orthopaedic surgeons and specialist on
      the hyperbaric medicine. First evaluation of HO effects should be done after 15
      expositions to HO. If effects are negative, treatment should continue till 25
      expositions. If effects are still negative, the treatment should terminate. As a
      part of complex treatment, HO can prevent high amputations, decrease the duration
      of hospitalisation and thus economise the whole therapy. Similar results were
      described in several clinical studies from different developed industrial
      countries.

PMID- 11284427
TI  - [Evaluation of stress in dialyzed patients].
AB  - BACKGROUND: Patients with chronic renal failure treated with hemodialysis are
      subjected to a high degree of stress. The aim of the study was to determine which
      components of stress become the most critical for the dialysed persons and how
      the degree of subjective stress depends on sex, age, and continuance of dialysis.
      METHODS AND RESULTS: 66 patients (40 females and 26 males) with chronic renal
      failure regularly treated with hemodialysis were included into the studied group.
      Average age was 57 years (26 to 75 years). Serial hemodialysis program lasted in
      average 51 months (4 to 144 months). Patients filled in the Scale of
      Hemodialysing Stressors, which contained 31 items, 6 of them physiological and 25
      psychosocial. Each stressor was ranked in four-point Likert's scale. Results were
      given in average values with standard deviation. To compare differences in
      subgroups, non-paired t-test was employed. Results showed that among the most
      serious stressors belongs the limitation of physical activity (average 1.91),
      limited possibilities for recreation (average 1.76), loss of body functions
      (average 1.68), fatigue (average 1.67), restriction of drinking (average 1.61).
      Average stress score for the whole scale was 32 +/- 11 with theoretically highest
      value of 93. Global stress score did not differ in males and females, in elderly
      patients (over 50 years) it was statistically higher than in younger ones (p <
      0.05) and in patients treated over one year it was higher than in those cured
      less long (p < 0.05). CONCLUSIONS: Dialysed patients are stressed namely by
      psychosocial factors. Most influenced are the older and for longer time dialysed
      patients. The short and long-lasting dialysis brings about similar level of
      stress. Stress can reach the highest level during the last year of the patient's
      life.

PMID- 11284428
TI  - [Health status of the population in six cities in the Czech Republic: prevalence
      and therapy of various chronic diseases].
AB  - BACKGROUND: The aim of the study was to describe health status of the urban
      middle-age population in six cities of the Czech Republic, which were included
      into the System of Population Health Survey in Relation to the Environment.
      METHODS AND RESULTS: From the population of cities Brno, Ceske Budejovice, Hradec
      Kralove, Karvina, Kolin, Usti nad Labem 400 males and 400 females in the age of
      45 to 54 years were included into the study. All respondents filled out a
      question-form, half of them also underwent a medical check up. Results has shown
      that 52.8% of males and 51.6% of females had their cholesterol level elevated (>
      5.2 mmol/l), 47.3% of males and 38.3% if females had higher blood pressure (SBP >
      = 140 mmHg and/or DBP > = 90 mmHg) or they were cured of hypertension, 39.4% of
      males and 22.5% of females were obese. Significant differences were observed in
      the prevalence of hypercholesterolemia, hypertension and smoking habits among the
      cities in study. According to the case histories, 55.6% of males and 57.8% of
      females complained of long-lasting ill-being, 37.0% of males and 45.2% of females
      were treated for a chronic disease, 13.3% of males and 12.4% of females
      considered their health during the previous year as bad or very bad. 45.4% of
      males and 57.9% of females underwent long-term pharmacological treatment, most
      frequently on a cardiovascular disease. Above described parameters differed
      significantly among cities in study. CONCLUSION: In the middle-aged population in
      six Czech cities the high prevalence of chronic diseases, health troubles and
      risk factors of chronic disease were found. Though the death rate in CR has been
      declining, chronic diseases have became a serious problem. Since most of these
      health problems can be improved by correct regimen, high attention should be
      given to their prevention.

PMID- 11284429
TI  - [Rehabilitation of patients with multiple sclerosis].
AB  - BACKGROUND: During the last decades a significant progress in rehabilitation of
      patients with multiple sclerosis (MS) has been achieved. This pilot study aims to
      study effect of weeks-lasting rehabilitation programme of MS patients in
      conditions of non-profiled inpatient rehabilitation unit. METHODS AND RESULTS:
      The rehabilitation program of 25 hospitalised patients was mostly aimed at
      complex kinesitherapy and physical therapy, partly also at ergotherapy and
      orthetics. Functional status of patients was evaluated at the beginning of the
      hospital stay and before dismission. Spasticity of lower limbs was scored using
      Global Assessment of Spasticity Scale (GSA) and modified Ashwort's scale. Motor
      subscore of Functional Independence Measure (FIM) was used to assess the
      patient's disability. In interval of 5 to 6 months a questionnaire was
      distributed among the patients to evaluate the rehabilitation stay. During the
      rehabilitation none of the studied patients got worse. At the beginning of
      hospitalisation average EDSS was 6.7 (median 6.5) +/- 1.0, before the demission
      it was 6.5 (6.5) +/- 0.9. Among the parameters studied statistically significant
      improvement came in the modified Ashwort's scale (from 2.5 +/- 0.8 to 1.8 +/-
      0.6) and in the motor subscore of Functional Independence Measure (from 59 +/- 15
      to 64 +/- 14). No statistically significant difference was found when the Global
      Assessment of Spasticity Scale was used--the improvement score of the group was
      1.0 +/- 0.7. Not all of questionnaires returned. The results obtained from
      responders showed positive evaluation of the rehabilitation program, which lasted
      for several months. CONCLUSION: Results of the study correspond to the literary
      data both in immediate effects of the treatment and in its persistence after
      dismission. As important reveals the fact that most of the patients has primary
      or secondary progressive MS. It can be reasonably presumed that further
      improvement of the rehabilitation of patients with neurological diseases could be
      achieved in specialised neurorehabilitation centres.

PMID- 11284430
TI  - [Prenatal diagnosis of de novo complex balanced rearrangements in chromosomes
      3,4, and 13] ].
AB  - A case of apparently balanced de novo complex chromosome rearrangement with three
      breaks found in foetus by amniotic fluid examination is described. Amniocentesis
      was indicated because of low AFP in maternal serum during the first pregnancy of
      25-year-old healthy woman. Her family anamnesis as well as her husbands on was
      insignificant, chromosomes were normal. Fetal karyotype was
      46,XY,t(3;13;4)(q26.2;q21.3;q12). To eliminate further cryptic aberrations the
      multicolor FISH technique was employed. The risk of serious inborn malformation
      in complex rearrangement with three breaks was estimated on the basis of literary
      data to be 10.5% (3.5% per each break). The couple decided to terminate the
      pregnancy. No distinct anomaly was found in the fetus. Only 12 prenatal diagnoses
      of the complex balanced chromosome rearrangements formed de novo can be found in
      the literature. Total risk of the serious malformation relating to that small
      group of described cases is rather high. Only substantial enlargement of the
      clinic may enable to use prenatal evaluation of each individual case according to
      the number of chromosomal breaks or according to other criteria with more
      accurate results.

PMID- 11284431
TI  - [Multicolor fluorescence in situ hybridization (mFISH].
AB  - Various techniques are now available for wide genome screening of alterations in
      copy number, structure and expression of genes and DNA sequences. Molecular
      cytogenetics has special techniques of comparative genomic hybridization (CGH),
      spectral karyotyping (SKY) and multicolor FISH (mFISH). We present principles of
      these methods, their use in molecular cytogenetic examinations of patients. We
      quote our experience with mFISH for analyses of complex chromosomal
      rearrangements in neoplastic cells and identification of inborn supernumerary
      marker chromosome. Further, we also review the first experiences with multicolor
      high resolution banding of chromosome (mBAND). This method was used for analysis
      of bone marrow cells of patient with myelodysplastic syndrome and deletion of
      chromosome No. 5. With mBAND exact breakpoints were localized. Multicolor
      fluorescence methods mFISH and mBAND becones the new tools for more precise
      analyses of inborn and acquired numerical and structural chromosomal
      rearrangements.

PMID- 11284432
TI  - A methodological strategy for PAH genotyping in populations with a marked
      molecular heterogeneity of hyperphenylalaninemia.
AB  - The elucidation of the molecular basis of hyperphenylalaninemia in various world
      populations (PKU Consortium Database: http://www.mcgill/ca/pahdb/) has revealed a
      remarkable molecular heterogeneity at the locus encoding for phenylalanine
      hydroxylase. As a consequence, genotyping of HPA patients has prompted the
      establishment of an impressive number of mutatIon detection protocols. In spite
      of the large variety of methods proposed so far, no comprehensive strategy has
      been yet developed for the detection of PAH gene mutations. Therefore, new
      approaches, combining the advantages of individual methods are required,
      especially in populations with a high number of PAH gene mutations. In this
      study, we propose the use of Reverse Dot Blot Analysis within a general mutation
      protocol to simplify the genotyping of hyperphenylalaninemics in the very
      heterogeneous population of Sicily (Italy).

PMID- 11284434
TI  - [What is the diagnosis and therapy in a chronic Mycoplasma pneumoniae
      infection?].

PMID- 11284433
TI  - Species-specific PCR for the identification of ovine, porcine and chicken species
      in meta and bone meal (MBM).
AB  - BSE, first identified in the UK in 1986 is thought to have arisen from feeding
      scrapie infected Meat and Bone Meal (MBM), produced under sub-optimal conditions,
      to cattle. For quality and safety reasons there is a requirement for a good
      analytical test for the surveillance of processed MBM. This study describes
      species-specific PCR assays for the identification of ovine, porcine and poultry
      species in MBM. A comparison between two distinct DNA extraction methods, i.e.
      the silicaguanidiumthiocyanate DNA isolation procedure and a commercial DNA
      extraction kit, is also presented. Application of this technology to species
      identification in industrial MBM was investigates as part of this study.

PMID- 11284435
TI  - Obituary. Bjorn Ekwall, MD.

PMID- 11284436
TI  - Retraction.

PMID- 11284437
TI  - Sex ratio at birth and latitude.

PMID- 11284439
TI  - Mitogen-activated protein kinases in the heart.

PMID- 11284438
TI  - Motor stimulant effects of the adenosine A2A receptor antagonist SCH 58261 do not
      develop tolerance after repeated treatments in 6-hydroxydopamine-lesioned rats.
AB  - Several evidences indicate that the selective blockade of adenosine A2A receptors
      counteracts the motor activity impairment in experimental models of Parkinson's
      disease. In the present study, the effects of the adenosine A2A receptor
      antagonist, SCH 58261 (5-amino-7-beta-phenylethyl)-2-(8-furyl)pyrazolo(4,3-e)
      1,2,4-triazolo(1,5-c)pyrimidine, were assessed following a repeated treatment
      schedule in the contralateral turning behavior rat model of Parkinson's disease.
      Unilateral lesions of the nigrostriatal pathway were induced by injecting 6
      hydroxydopamine (6-OHDA in medial forebrain bundle. Repeated administration of
      SCH 58261 was performed either alone (7 and 14 days repeated SCH 58261) or
      together with L-dopa (19 days repeated SCH 58261 plus L-dopa or L-dopa alone).
      After a 7- and 14-day repeated administration schedule, SCH 58261 (5 mg/kg)
      maintained its ability to potentiate the contralateral turning behavior induced
      by a subthreshold dose of L-dopa (2 mg/kg i.p.), showing no tolerance to its
      stimulant effects. SCH 58261 (5 mg/kg) plus L-dopa (3 mg/kg) or L-dopa (6 mg/kg)
      alone induced, at these dosages, the same number of contralateral turnings after
      the first administration. While chronic intermittent SCH 58261 plus L-dopa did
      not lead to a modified turning behavior during treatment, L-dopa alone produced a
      progressive increase in turning behavior intensity and duration. These results
      provide evidence that SCH 58261 retains its ability to potentiate L-dopa effects
      in a validated rat model of Parkinson's disease even after repeated treatments.
      Moreover, these results suggest that adenosine A2A blockade prevents the
      appearance of motor response alterations in L-dopa-treated rats, supporting the
      concept that A2A receptor antagonists have a therapeutic potential for the
      treatment of Parkinson's disease

PMID- 11284440
TI  - Protective effects of yangambin on cardiovascular hyporeactivity to
      catecholamines in rats with endotoxin-induced shock.
AB  - The protective effects of a new, selective, plant-derived platelet-activating
      factor (PAF) antagonist, yangambin, on the cardiovascular alterations and
      mortality due to endotoxic shock were investigated in anaesthetized rats. We also
      studied the involvement of PAF in the induction of the vascular and cardiac
      hyporesponsiveness to adrenergic stimulation observed during endotoxaemia. The
      animals were sensitized to the lethal effects of Escherichia coli
      lipopolysaccharide (LPS) with D(+)-galactosamine (50 mg/kg, i.v.) 15 min before
      LPS injection. LPS (3 mg/kg, i.v.) induced a progressive and marked decrease in
      mean arterial blood pressure from 85+/-4 to 30+/-3 mmHg and a reduction of
      cardiac output (CO) from 180+/-7 to 37+/-3 ml/min (120 min) accompanied by a
      maintenance of systemic vascular resistance, suggesting that cardiovascular
      collapse resulted mainly from myocardial depression. The maximum pressor
      responses to noradrenaline (0.3-3.0 microg/kg, i.v.) fell from 72+/-9 (control)
      to 5+/-1 mmHg (LPS) while the CO responses decreased from 81+/-5 to 8+/-3 ml/min.
      Pre-treatment with yangambin (30 mg/kg, i.v.) or with WEB 2086 (5 mg/kg, i.v.), a
      reference PAF receptor antagonist, completely prevented the LPS-induced
      cardiovascular collapse and abolished the sharp reductions of the arterial blood
      pressure and CO responses to noradrenaline observed during endotoxaemia. Post
      treatment with yangambin 90 min after LPS administration did not reverse the
      arterial hypotension, cardiac failure or cardiovascular hyporesponsiveness to
      catecholamines. Finally, the acute (150 min) survival rates of endotoxic shock
      increased from 0% (LPS group) to 100% in the groups pretreated with either
      yangambin or WEB 2086. The long-term (7-day) survival also increased from 0% (LPS
      group) to 85% (yangambin pre-treatment group). In conclusion, these data suggest
      a role for PAF in the pathogenesis of endotoxin-induced vascular and cardiac
      hyporesponsiveness to catecholamines and confirm its involvement in the complex
      cascade of multiple mediators released during endotoxic/septic shock. Yangambin
      proved to be an effective pharmacological agent against cardiovascular collapse
      and mortality in endotoxin shock.

PMID- 11284441
TI  - Endotoxin inhibits gastric emptying in rats via a capsaicin-sensitive afferent
      pathway.
AB  - The effects of endotoxin on gastric emptying of a solid nutrient meal and the
      neural mechanisms involved in such a response were investigated in conscious
      rats. The intraperitoneal (i.p.) administration of E. coli endotoxin (40
      microg/kg) significantly reduced the 4-h rate of gastric emptying of a standard
      solid nutrient meal. Ablation of primary afferent neurons by systemic
      administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats did
      not modify the rate of gastric emptying in control animals but prevented the
      delay in gastric transit induced by endotoxin. Local application of capsaicin to
      the vagus nerve rather than application of capsaicin to the celiac ganglion
      significantly repressed endotoxin-induced delay in gastric emptying. Neither
      treatment modified the rate of gastric emptying in vehicle-treated animals.
      Blockade of CGRP receptors (CGRP 8-37, 100 microg/kg i.v.) did not alter gastric
      emptying in control animals but significantly prevented endotoxin-induced
      inhibition of gastric emptying. In contrast, a tachykinin receptor antagonist ([D
      Pro2, D-Trp7.9]-substance P, 2 mg/kg i.p.) significantly reduced the rate of
      gastric emptying in control animals and did not modify the inhibitory effects of
      endotoxin. Adrenergic blockade with phentolamine (3 mg/kg i.p.) +/- propranolol
      (5 mg/kg i.p.) or muscarinic antagonism with atropine (0.1 mg/kg i.p.) failed to
      reverse the delay in gastric emptying induced by endotoxin. These observations
      indicate that endotoxin-induced delay in gastric emptying of a solid nutrient
      meal is mediated by capsaicin-sensitive afferent neurons.

PMID- 11284442
TI  - Effects of icatibant on the ramipril-induced decreased in renal lithium clearance
      in the rat.
AB  - The interaction between an inhibitor of angiotensin I converting enzyme
      (ramipril) and renal lithium handling was analysed in conscious, normotensive
      Wistar rats in the absence or the presence of a specific bradykinin B2 receptor
      antagonist, icatibant. The rats were treated for 5 days with ramipril (1
      mg/kg/day p.o.) or its vehicle, alone or together with icatibant (0.1 mg/kg/day,
      s.c. infusion). Lithium chloride (8.3 mg/kg i.p.) was given as a single dose on
      day 5. Systolic blood pressure and heart rate were measured by tail
      plethysmography on day 3 (3, 9 and 15 h after ramipril administration) and renal
      function on day 4 (0-6 and 6-24 h urine sampling) and day 5 (0-6 h urine
      sampling). In another group of rats, 24 h sodium excretion was assessed during
      the first 4 days of ramipril treatment. Ramipril decreased renal lithium
      clearance (90+/-8 vs. 142+/-10 microl/min/100 g, P<0.001, n=24) and increased the
      fractional lithium reabsorption (74.3+/-1.9 vs. 66.7+/-1.7%, P<0.05) and plasma
      lithium concentration (0.108+/-0.006 vs. 0.085+/-0.004 mM, P<0.01). Alteration of
      renal lithium handling by ramipril was associated with a decrease in systolic
      blood pressure (-15% 3 h after ramipril administration) and sodium excretion (0-6
      h after ramipril). The 24-h sodium excretion, however, tended to increase.
      Icatibant had no effect per se on renal function but attenuated the ramipril
      induced decrease in renal lithium clearance (118+/-16 vs. 90+/-8 microl/min/100
      g, n=12 and 24 respectively, P<0.05 one-tailed test) and systolic blood pressure.
      These results suggest that endogenous bradykinin contributes to the ramipril
      associated alteration in renal lithium handling. Bradykinin B2 receptor-mediated
      vasodilation seems to be involved.

PMID- 11284443
TI  - Sensitization to the behavioural effects of cocaine: alterations in tyrosine
      hydroxylase or endogenous opioid mRNAs are not necessarily involved.
AB  - After repeated administration of cocaine at intervals, sensitization phenomena
      can be observed, so that its behavioural effects are enhanced. Since this
      phenomenon is long-lasting, it was of interest to study which persistent
      alterations in the activity of dopaminergic neurones or of endogenous opioid
      systems downstream of dopaminergic synapses in the basal ganglia are involved in
      the sensitization. Cocaine (10 mg/kg i.p.) was administered to rats on days 1, 3,
      5 and 7 and saline on days 2, 4 and 6 ("repeated cocaine"), or saline was
      injected on days 1-6 and cocaine on day 7 ("acute cocaine"), or saline was
      injected on days 1-7 ("saline group"). The "repeated cocaine" schedule led to a
      significant sensitization to the locomotor activation produced by cocaine on day
      7 or on day 17, 10 days after the end of sensitization protocol. Microdialysis in
      the nucleus accumbens which was performed after administration of cocaine (10
      mg/kg i.p.) on day 7, or after an administration of the same dose 10 days after
      the last administration of cocaine, respectively, revealed significant acute
      increases of extracellular dopamine to about 200% of basal values. These
      increases were similar in "acute cocaine" and in "repeated cocaine" animals both
      after 7 days and after 17 days. For in situ hybridization studies, rats were
      sacrificed on day 7, 4.5 h after the last cocaine or saline administration. The
      mRNA for tyrosine hydroxylase (TH) in substantia nigra + ventral tegmental area
      was significantly elevated to about 140% of saline controls both in the "repeated
      cocaine" and the "acute cocaine" group as compared with the "saline group". In
      contrast, there were no differences between the three groups in the mRNAs of
      preprodynorphin or preproenkephalin levels measured in the nucleus accumbens
      (core and shell). These results suggest that sensitization phenomena to cocaine
      are not necessarily connected with alterations in the dopaminergic activity in
      the mesolimbic system or in the transcription of precursors of endogenous opioid
      peptides which are located downstream of the dopaminergic synapses.

PMID- 11284444
TI  - Activation of a Ca2+-dependent K+ current in mouse fibroblasts by sphingosine-1
      phosphate involves the protein tyrosine kinase c-Src.
AB  - Sphingosine-1-phosphate (S1P) is a phospholipid that acts through G-protein
      coupled plasma membrane receptors and induces a broad spectrum of cellular
      responses, including proliferation, migration, differentiation and apoptosis.
      Here we report that in NIH3T3 and C3H10T1/2 mouse fibroblasts S1P activates a
      Ca2+-dependent, voltage-independent K+ current (EC50-value 113 nM) that is
      blocked by the K+ channel blockers charybdotoxin, margatoxin, and iberiotoxin.
      The K+ current activation by S1P is transient and leads to a large membrane
      hyperpolarization. Recently, we showed that lysophosphatidic acid (LPA), a serum
      lipid with similar biological effects compared to those of S1P, can activate a
      Ca2+-dependent K+ current in NIH3T3 cells that has identical properties compared
      to the one that is activated by S1P. When applied consecutively, both S1P and LPA
      induced a K+ current response in NIH3T3 cells, which indicates that the K+
      current activation is not subjected to cross-desensitization between S1P and LPA.
      In C3H10T1/2 mouse fibroblasts that overexpress the nonreceptor protein tyrosine
      kinase c-Src, the amplitude of the S1P-induced K+ current was almost doubled
      compared to the one that we found in control cells. Expression of a non
      myristylated c-Src mutant led to a further increase in the K+ current response to
      S1P, whereas expression of a kinase-defective c-Src mutant reduced it to about
      40% compared to the control value. Our data show that S1P activates Ca2+
      dependent K+ channels in mouse fibroblasts via an intracellular signalling
      pathway that involves the non-receptor protein tyrosine kinase c-Src.

PMID- 11284445
TI  - Regulatory role of nitric oxide over hippocampal 5-HT release in vivo.
AB  - Previous work has shown that N-methyl-D-aspartate (NMDA) receptor activation
      decreases 5-hydroxytryptamine (5-HT) release in the hippocampus of freely moving
      rats. Given the association between NMDA receptor function and nitric oxide (NO)
      production with the regulation of 5-HT release in other brain regions, we have
      studied this in rat hippocampus. NMDA (100 microM) decreased hippocampal 5-HT
      release by approximately 70% and this was reversed by the NMDA receptor
      antagonist 2-amino-5-phosphonopentanoic acid (AP5; 10 microM). The NO donor S
      nitroso-N-acetylpenicillamine (SNAP) had an inverse concentration-dependent
      effect on 5-HT release. At 500 microM, SNAP elevated dialysate 5-HT by 55% over
      basal, while at 5 mM a 70% decrease was seen. The non-selective nitric oxide
      synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) at 1 mM
      increased extracellular 5-HT, although a return to basal levels occurred despite
      the continued presence of the drug. At 1 mM L-NAME prevented the decrease in 5-HT
      elicited by NMDA (100 microM) infusion. 7-Nitroindazole (7-NI), a relatively
      selective neuronal NOS (nNOS) inhibitor, decreased extracellular 5-HT at 100
      microM and 1 mM. When 100 microM 7-NI was infused for 60 min prior to NMDA, 5-HT
      levels were transiently increased above basal before returning to control levels.
      Following combined application of the two drugs, no decrease in dialysate 5-HT
      was seen. Our data support a role for NO in modulating both basal and NMDA-evoked
      changes in 5-HT release in the hippocampus, however, the association appears to
      be complex. It may be that the recorded changes in 5-HT release are secondary to
      changes in the release of amino acid transmitters which we have previously found
      to be dependent on the prevailing extracellular NO concentration.

PMID- 11284446
TI  - The influence of tumour necrosis factor-alpha on the cardiovascular system of
      anaesthetized rats.
AB  - The effects of two vasoactive agents (adenosine A2A agonist, CGS 21680, and
      adrenoceptor agonist, noradrenaline) were examined on cardiac output (CO), heart
      rate (HR), blood pressure (BP), mean circulatory filling pressure (Pmcf),
      resistance to venous return, arterial resistance, dP/dt, plasma levels of NO2
      /NO3-, and inducible nitric oxide synthase (iNOS) activity in lungs ex vivo,
      following treatment with tumour necrosis factor-alpha (TNF-alpha; 30 microg/kg)
      in anaesthetized rats. Treatment with TNF-alpha produced significant reduction in
      CO (41+/-2%), dP/dt (26+/-3%), BP (26+/-2%) and Pmcf (27+/-4%; n=6; mean+/-SEM),
      but increased arterial resistance. There were no significant changes in the
      plasma levels of NO2-/NO3-levels over time following treatment with TNF-alpha,
      but there was a significant increase (approximately twofold) in the activity of
      the iNOS in the lungs of animals treated with TNF-alpha. Administration of CGS
      21680 (1.0 microg/kg per min) significantly increased CO (44+/-6%), HR (12+/-2%),
      Pmcf (24+/-4%) and dP/dt (24+/-5%) in TNF-alpha-treated rats. CGS 21680 also
      significantly reduced arterial resistance (33+/-2%) without altering resistance
      to venous return in TNF-alpha-treated rats. While noradrenaline (1.0 microg/kg
      per min) infusion did not significantly increase CO, it did significantly
      increase HR (12+/-1%), BP (55+/-9%), Pmcf (47+/-5%), dP/dt (65+/-7%), resistance
      to venous return (64+/-20%), and arterial resistance (41+/-16%) in TNF-alpha
      treated animals. The reduction in BP due to administration of TNF-alpha is the
      result of significant reduction in CO. Consequently, the decline in CO can be
      attributed to a combination of a negative inotropic effect as well as a reduction
      in Pmcf. It is evident that infusion with CGS 21680 could reverse the negative
      impact of TNF-alpha on CO by increasing dP/dt, Pmcf and HR as well as a reduction
      in arterial resistance. The fact that noradrenaline did not significantly
      increase CO in TNF-alpha-treated rats can be attributed to increased arterial
      resistance as well increase in resistance to venous return.

PMID- 11284447
TI  - Inositolphosphate formation in thoracic and abdominal rat aorta following Gq/11
      coupled receptor stimulation.
AB  - Although thoracic and abdominal rat aorta are often used as a classical
      pharmacological preparation for the assessment of vascular drug effects, little
      is known on regional differences among these two parts of the aorta with regard
      to their reaction to Gq/11-coupled receptor activation. Thus, we determined, in
      rings from thoracic and abdominal aorta from 12-week-old male Wistar rats, the
      effects of noradrenaline (NA; 10(-8)-10(-4) M), endothelin-1 (ET-1; 10(-10)-10(
      6) M) and the thromboxane A2 mimetic U 46619 (10(-8)-10(-5) M) on
      inositolphoshate (IP) formation (assessed as accumulation of total [3H]IPs in
      [3H]myoinositol prelabelled rings). NA, ET-1 and U 46619 concentration
      dependently increased IP formation; maximum increases were, however,
      significantly more pronounced in thoracic than in abdominal aorta. Similarly, NA,
      ET-1 and U 46619 evoked significantly larger maximum contractions in thoracic
      than in abdominal aorta. NA-induced [3H]IP formation could be inhibited with BMY
      7378 (10(-9)-10(-4) M) and with 5-methyl-urapidil (5-MU; 10(-9)-10(-5) M) both
      exhibiting biphasic concentration-inhibition curves. The pKi-values for BMY 7378
      at the high affinity site were in thoracic aorta 8.93+/-0.28 (n=5), and in
      abdominal aorta 8.76+/-0.35 (n=4) and at the low affinity site 6.45+/-0.2
      (thoracic aorta) and 6.55+/-0.27 (abdominal aorta). pKi-Values for 5-MU in
      thoracic aorta at the high affinity site were 8.25+/-0.34 (n=4), and at the low
      affinity site 6.61+/-0.39 . In abdominal aorta reliable pKi-values could not be
      calculated for 5-MU due to a low signal-to-noise ratio. On the other hand, in
      both preparations the ETA-receptor antagonist BQ-123 (10(-9)-10(-5) M) and the TP
      receptor antagonist SQ 29548 (10(-9)-10(-5) M) inhibited ET-1- and U 46619
      induced IP formation, respectively, with monophasic concentration-inhibition
      curves: pKi-values for BQ-123 were: 8.16+/-0.24 (thoracic aorta) and 8.10+/-0.35
      (abdominal aorta) and for SQ 29548: 8.2+/-0.3 (thoracic aorta) and 8.5+/-0.3
      (abdominal aorta). The amount of immunodetectable Gq/11-protein was similar in
      both tissues. We conclude that responses to NA, ET-1 and U 46619 (IP formation
      and contractile force) are larger in thoracic than in abdominal aorta. ET-1
      effects on IP formation are mediated by ETA-receptors and U 46619 effects by TP
      receptors. NA effects are mediated by alpha1D- and alpha1A-adrenoceptors; alpha1B
      adrenoceptors seem to play a minor role.

PMID- 11284448
TI  - Influence of retigabine on the anticonvulsant activity of some antiepileptic
      drugs against audiogenic seizures in DBA/2 mice.
AB  - Retigabine (D-2319, 0.5-20 mg/kg i.p.) antagonised dose dependently audiogenic
      seizures in DBA/2 mice. Retigabine at 0.5 mg/kg i.p., a dose that per se did not
      affect the occurrence of audiogenic seizures significantly, potentiated the
      anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine,
      phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2
      mice. The degree of additivity for the effect induced by retigabine was greatest
      for diazepam, phenobarbital, phenytoin and valproate, less for carbamazepine and
      lamotrigine and least for felbamate. The increase in anticonvulsant activity was
      usually associated with a comparable increase in motor impairment. However, the
      therapeutic index of combined treatment (drugs plus retigabine), was more
      favourable than the same drug plus vehicle. Since retigabine had no significant
      influence on the total and free plasma levels of the anticonvulsant drugs,
      pharmacokinetic interactions, in terms of total or free plasma levels, are not
      probable. However, the possibility that retigabine modifies the clearance of the
      anticonvulsant drugs from the brain cannot be excluded. Retigabine had no
      significant effect on the hypothermic effects of the anticonvulsants tested. In
      conclusion, retigabine showed an additive effect when administered in combination
      with classical anticonvulsants, most notably diazepam, phenobarbital, phenytoin
      and valproate.

PMID- 11284449
TI  - P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta
      acetyldigoxin.
AB  - Digoxin is a drug with a narrow therapeutic index, which is substrate of the ATP
      dependent efflux pump P-glycoprotein. Increased or decreased digoxin plasma
      concentrations occur in humans due to inhibition or induction of this drug
      transporter in organs with excretory function such as small intestine, liver and
      kidneys. Whereas particle size, dissolution rate and lipophilic properties have
      been identified as determinants for absorption of digitalis glycosides, little is
      known about P-glycoprotein transport characteristics of digitalis glycosides such
      as digitoxin, alpha-methyldigoxin, beta-acetyldigoxin and ouabain. Using
      polarized P-glycoprotein-expressing cell lines we therefore studied whether these
      compounds are substrates of P-glycoprotein. Polarized transport of digitalis
      glycosides was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells (LLC
      PK1 cells stably transfected with the human MDR1 P-glycoprotein). Inhibition of P
      glycoprotein-mediated transport of these compounds in Caco-2 cells was determined
      using the cyclosporine analogue PSC-833 (valspodar) as inhibitor of P
      glycoprotein. No polarized transport was observed for ouabain. However, basal-to
      apical transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin was
      greater than apical-to-basal transport in Caco-2 and L-MDR1 cells. In Caco-2
      cells net transport rates of these compounds were similar to those of digoxin
      (digoxin: 16.0+/-4.4%, digitoxin: 15.0+/-3.3%, beta-acetyldigoxin: 16.2+/-1.6%,
      alpha-methyldigoxin: 13.5+/-4.8%). Furthermore, polarized transport of these
      compounds could be completely inhibited by 1 microM PSC-833. In summary, these
      data provide evidence that not only digoxin, but also digitoxin, alpha
      methyldigoxin and beta-acetyldigoxin are substrates of P-glycoprotein.

PMID- 11284450
TI  - HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive
      and -insensitive contraction of the isolated rabbit aorta.
AB  - The vasorelaxant profile of a novel azulene-1-carboxamidine derivative, HNS-32
      [N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethyl-azulene-1
      carboxamidine, CAS 186086-10-2], was investigated in the isolated rabbit aorta
      precontracted with high KCl, noradrenaline (NA) or phorbol 12, 13-dibutyrate
      (PDBu) and compared with those of nifedipine and nitroglycerin. In preparations
      without endothelium, HNS-32 elicited concentration-dependent, full inhibition of
      contractions elicited by high KCI (80 mM), NA (3x10(-6) M) or PDBu (10(-6) M). In
      contrast, nifedipine inhibited only the contraction elicited by membrane
      depolarization with high KCl. Nitroglycerin also attenuated high-KCl-, NA- and
      PDBu-elicited contractions effectively, although full suppression was obtained
      only for NA-elicited contraction. Whilst the relaxant effect of HNS-32 was not
      affected by the presence of endothelium, the relaxant response to acetylcholine
      was endothelium dependent. Addition of excess Ca2+ restored both the HNS-32
      reduced tension in muscle precontracted with high KCI and the nifedipine-mediated
      tension decrease. Relaxation elicited by HNS-32 was not affected by the adenylate
      cyclase inhibitor, 9-(tetrahydro-2'-furyl)adenine (SQ 22,536, 10(-4) M), the
      soluble guanylate cyclase inhibitor, 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1
      one (ODQ, 10(-5) M) or a cocktail of K+ channel blockers (glybenclamide 10(-6) M,
      tetraethylammonium 2x10(-3) M, apamin 10(-7) M, 4-aminopyridine 10(-4) M and Ba2+
      10(-5) M). These findings indicate that HNS-32 inhibits both L-type Ca2+ channel
      dependent and -independent vascular contraction. Blockade of Ca2+ entry through L
      type Ca2+ channels may be involved in the inhibitory effect of HNS-32 on the
      contraction due to membrane depolarization with high KCl. On the other hand, HNS
      32 seems to inhibit Ca2+ channel-independent contraction via mechanism(s) other
      than elevation of cyclic nucleotides (cAMP and cGMP) and opening of K+ channels.

PMID- 11284451
TI  - Nitric oxide synthases and cyclophosphamide-induced cystitis in rats.
AB  - The role of inducible (iNOS) and neuronal nitric oxide (nNOS) synthases and of
      tachykinin NK1 receptors on the pathogenesis of cyclophosphamide (CYP)-induced
      cystitis was investigated, in rats. CYP-induced cystitis was characterized by
      large increases in bladder-protein plasma extravasation (PPE), increases in the
      urinary excretion of nitric oxide (NO) metabolites and histological evidences of
      urothelial damage, edema, extensive white blood cell infiltrates and vascular
      congestion of the bladder. The specific iNOS inhibitor, S-methylthiourea (MITU),
      produced marked inhibition (>90%) of CYP-induced increases in PPE associated with
      amelioration of tissue inflammatory changes. Treatment with 7-nitroindazole (7
      NI; 20, 40 and 80 mg/kg), a selective nNOS inhibitor, did not significantly
      reduce CYP-induced increases in PPE and failed to produce histological
      improvement. In addition, treatment with MITU, but not with 7-NI, inhibited the
      increases in the urinary excretion of NO metabolites induced by CYP treatment.
      WIN 51,708 (17-beta-hydroxy-17-alpha-ethynyl-androstano[3,2-b]pyrimido[1,2
      a]benzimidazole; WIN), a selective NK1-receptor antagonist, reduced the increases
      in EPP and ameliorated the inflammatory changes in the bladder induced by CYP.
      However, the maximal degree of protection achieved with WIN was significantly
      less than that produced by MITU. Combined treatment with the iNOS inhibitor and
      the NK1 antagonist produced no greater effect than that produced by the iNOS
      inhibitor alone. Our results suggest that NO plays a fundamental role in the
      production of the cystitis associated with CYP treatment. The iNOS, and not nNOS,
      seems responsible for the inflammatory changes. Part of the increases in NO may
      due to activation of NK1 receptors by neuropeptides such as substance P possibly
      released from primary afferent fibers.

PMID- 11284452
TI  - Localisation of mRNA for h5-HT1B and h5-HT1D receptors in human dorsal raphe.
AB  - In the mammalian mesencephalon, virtually all serotoninergic neurons are located
      in the raphe nuclei and the adjacent reticular formation. Pharmacological
      evidence obtained in rodents suggests that terminal and somatodendritic
      autoreceptors controlling serotonin (5-hydroxytryptamine, 5-HT) release belong to
      the 5-HT1B/D subtype of receptors, whereas somatodendritic autoreceptors
      controlling neuronal cell firing are predominantly of the 5-HT1A subtype. This
      study investigated the presence of h5-HT1D and h5-HT1B receptor mRNA within the
      subdivisions of the dorsal raphe of post-mortem human brains by means of in situ
      hybridisation. Although differences in the labelling intensity, which may be
      caused by different pre- and/or post-mortem conditions, were obvious among the
      specimens, all brains expressed both the h5-HT1D and the h5-HT1B mRNA in dorsal
      raphe neurons. In comparison to h5-HT1D mRNA, expression of h5-HT1B mRNA was
      slightly more abundant. Information on the existence and localisation of h5-HT1D
      and h5-HT1B receptors in human dorsal raphe neurons confirms that both subtypes
      may serve an autoreceptor function in humans. This finding is of pharmacological
      relevance since these receptors are potential new targets for therapeutic
      interventions in psychiatric disorders such as depression and anxiety.

PMID- 11284453
TI  - An improved high-performance liquid chromatographic method for the determination
      of sphingosine-1-phosphate in complex biological materials.
AB  - Sphingosine-1-phosphate (SPP) has been proposed to act both as an intracellular
      second messenger and as an extracellular mediator via specific cell surface
      receptors. Based on the increasing diverse cellular roles methods to quantify
      endogenous and exogenous SPP are highly required. Here, we report a rapid HPLC
      method that allows quantification of SPP in the picomolar range even in complex
      biological systems. A two-step lipid extraction serves to separate SPP from most
      interfering phospholipids and sphingolipids. Importantly, dihydrosphingosine-1
      phosphate (dihydro-SPP), not detectable in all cultured cells and biological
      samples in considerable amounts, possesses equal extraction properties and
      therefore is an ideal internal standard. Following extraction SPP and dihydro-SPP
      are converted to fluorescent isoindol derivatives by ortho-phthaldialdehyde (OPA)
      and separated by HPLC using a gradient program with methanol and 0.07 M K2HPO4 as
      eluents. With this procedure we were able to obtain reproducible measurements of
      SPP over a broad range from 0.5 pM to 0.2 nM. The identity of SPP and dihydro-SPP
      was confirmed by the use of the ion pair reagent tetraammoniumsulfate, which
      induced a shift of both peaks but did not alter peak areas. Moreover, enzymatic
      conversions to sphingosine and sphinganine by bovine intestinal mucosa alkaline
      phosphatase (AP) excluded the existence of overlapping compounds. Levels of SPP
      were determined in a variety of biological samples like serum, thrombocytes,
      primary keratinocytes and several cell lines. Furthermore, we were able to detect
      increases of intracellular SPP levels in human keratinocytes after exposure to
      1alpha,25-dihydroxyvitamin D3(1,25-(OH)2D3) for which a stimulation of
      sphingosine kinase activity has been recognized.

PMID- 11284454
TI  - Epithelial ingrowth after laser in situ keratomileusis.

PMID- 11284455
TI  - Effect of intensive exercise on patients with active RA.

PMID- 11284456
TI  - Pulmonary function in patients with primary Sjogren's syndrome.

PMID- 11284457
TI  - RS3PE and ovarian cancer.

PMID- 11284458
TI  - Differential expression of cytokines and nitric oxide synthase isoforms in human
      rotator cuff bursae.

PMID- 11284459
TI  - Is parenteral methotrexate worth trying?

PMID- 11284460
TI  - Outcome of juvenile headache in outpatients attending 23 Italian headache
      clinics. Italian Collaborative Study Group on Juvenile Headache (Societa Italiana
      Neuropsichiatria Infantile [SINPI]).
AB  - A multicenter 3-year follow-up study was carried out on young patients with
      headache referred to tertiary headache centers or pediatric clinics. Three years
      after the first examination in 1993, 442 (of an original sample of 719) young
      outpatients with headache (226 females and 216 males) were re-examined. The
      diagnostic criteria of the International Headache Society (IHS) and those
      modified for migraine without aura by Winner et al were applied at both the
      baseline evaluation and the 3-year re-examination. At the follow-up, 290 children
      still had headache, 101 were in clinical remission, and 51 had dropped out. Using
      the current diagnostic criteria, only 46.2% of patients having migraine without
      aura, 50% of those having migraine with aura, and 35.3% of those suffering from
      migraine disorders which do not fulfill IHS criteria for migraine received the
      same diagnosis at the time of follow-up. The percentage of patients receiving a
      diagnosis of migraine without aura rose significantly when new modified criteria
      were used (60.5%), whereas a drop in the frequency of migraine disorders not
      fulfilling IHS criteria was observed at follow-up, both in patients with the
      diagnosis of migraine without aura at the first examination (4.6%) and in
      patients with migraine not always fulfilling IHS criteria at the first
      examination (6.2%). Among all patients who received this latter diagnosis at the
      first examination, it was possible to make a diagnosis of migraine with aura at
      the follow-up in 8.8% of cases and that of migraine without aura in 26.5%. No
      significant variations in the frequency of either episodic tension-type headache
      or chronic tension-type headache were found, with the exception of a slight
      decrease in the percentage of tension-type headache which did not fulfill IHS
      criteria, but the difference between the first examination and the follow-up
      values does not reach the level of statistical significance (5% versus 12%). As
      far as the evolution of migraine is concerned, 17.4% of patients with migraine
      were headache-free at the 3-year follow-up. In tension-type headache, the
      percentage of patients who were headache-free was particularly high in those with
      the episodic form (32.9%) and in those suffering from tension-type headache not
      fulfilling IHS criteria (29.1%). The majority of patients who had been diagnosed
      as having unclassifiable headache at the first examination received a correct
      diagnosis at the follow-up with the exception of one patient. As observed in
      adult patients, variations in the headache characteristics were also observed in
      children and adolescents (that is, migraine with aura can change to migraine
      without aura, or the latter can transform into episodic tension-type headache or
      chronic tension-type headache can change into the episodic form). This follow-up
      study was aimed at reaching a better understanding of headache disturbances in
      children and adolescents, examining, in particular, variations of headache with
      time in this stage of life.

PMID- 11284461
TI  - Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term
      study. Long-term Safety of Depakote in Headache Prophylaxis Study Group.
AB  - CONTEXT: The adverse event profile of long-term divalproex therapy for epilepsy
      is well established, but little is known about the tolerability or safety of
      divalproex in long-term migraine prophylaxis. OBJECTIVE: Evaluate the long-term
      safety and efficacy of divalproex sodium in migraine prophylaxis. DESIGN: Open
      label, long-term study, of up to 3 years, of patients who completed one of two
      multicenter, double-blind, randomized, placebo-controlled studies. SETTING:
      Eighteen headache/neurology centers throughout the United States. PATIENTS: One
      hundred sixty-three patients: 46 treated with placebo, 117 treated with
      divalproex for migraine in previous studies. INTERVENTION: Divalproex therapy
      initiated at 500 mg/day (250 mg twice daily), with adjustment in dose and dosing
      frequency possible after 1 to 3 days. MAIN OUTCOME MEASURES: Number and
      proportion of patients reporting treatment-emergent adverse events, prevalence
      and incidence for each treatment-emergent adverse event, vital signs, body
      weight, 4-week migraine rates and proportion of patients with 50% or greater
      reduction in rate over time. RESULTS: Treatment lasted more than 180 days for 71%
      of patients and more than 360 days for 48% of patients. Improvements in the 4
      week, change-from-baseline migraine rates were seen during each of the 3- and 6
      month time intervals. CONCLUSIONS: Divalproex is effective for migraine
      prophylaxis, and initial benefits are maintained for periods in excess of 1080
      days.

PMID- 11284462
TI  - Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and
      50 mg in migraine. Rizatriptan Protocol 046 Study Group.
AB  - Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption
      and early onset of action in the acute treatment of migraine. This double-blind,
      placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan
      25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients
      were allocated to one of five groups for treatment of two attacks: rizatriptan 5
      mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10
      mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For
      each attack, patients rated headache severity, presence of associated symptoms,
      and functional disability prior to dosing and at intervals through 4 hours
      thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5
      mg and 10 mg provided faster relief of headache pain and greater relief of
      migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively.
      The response to rizatriptan was better than sumatriptan on additional measures
      including functional disability and satisfaction with medication. All active
      treatments were highly effective compared to placebo and acted as early as 30
      minutes after dosing. All active treatments were well-tolerated and showed
      comparable safety profiles.

PMID- 11284463
TI  - Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute
      treatment of migraine. Rizatriptan 030 Study Group.
AB  - Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and
      higher bioavailability than oral sumatriptan. It was postulated that this would
      result in more rapid onset of effect. This randomized, double-blind, triple
      dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg,
      sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine
      attack. Headache relief rates after rizatriptan 10 mg were consistently higher
      than sumatriptan at all time points up to 2 hours, with significance at 1 hour
      (37% versus 28%, P = 0.010). All active agents were significantly superior to
      placebo with regard to headache relief and pain freedom at 2 hours (P < or =
      0.001). The primary efficacy endpoint of time to pain relief through 2 hours
      demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had
      earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan
      10 mg was also superior to sumatriptan on pain-free response (P = 0.032),
      reduction in functional disability (P = 0.015), and relief of nausea at 2 hours
      (P = 0.010). Significantly fewer drug-related clinical adverse events were
      reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100
      mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and
      relieves headache and associated symptoms more effectively than sumatriptan 100
      mg.

PMID- 11284464
TI  - Efficacy and safety of rizatriptan versus standard care during long-term
      treatment for migraine. Rizatriptan Multicenter Study Groups.
AB  - Rizatriptan is a novel, selective 5-HT1B/1D receptor agonist with a rapid onset
      of action after oral dosing for the acute treatment of migraine. We conducted a
      long-term (up to 1 year), multicenter, randomized study in 1831 patients treating
      more than 46,000 attacks to compare the efficacy and tolerability of rizatriptan
      5 mg and 10 mg to standard care medications routinely used for the acute
      treatment of migraine attacks. Both doses of rizatriptan were highly effective,
      without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior (P
      < 0.05), both to the 5-mg dose and to standard care, in providing relief in 90%
      of attacks, with 50% pain-free by 2 hours after dosing. The most common dose
      related adverse events were nausea, somnolence, and asthenia/fatigue. Based on
      this large, multicenter, long-term trial, rizatriptan is an important new oral
      agent for the acute treatment of migraine.

PMID- 11284465
TI  - [Obstetrical acute renal failure. Experience of the nephrology department,
      Central University Hospital ibn Rochd, Casablanca].
AB  - The gravidic acute renal failure (ARF) becomes a rare complications of the
      pregnancy in the industrialized countries, whereas it is still frequent in the
      developing countries and responsible of great maternofetal morbidity and
      mortality. We studied the etiologic and evolutive aspects of the gravidic ARF in
      55 patients during 18 years (1981-1998) at the department of nephrology, hospital
      center Ibn Rochd in Casablanca. The gravidic ARF represents 65% of the gravidic
      patients. The mean age of the patients is 30.92 +/- 6.44 years old. The mean
      parity is 3.38 +/- 2.25. The mean term is 31.73 +/- 10.02 weeks of amenorrhea.
      The main etiology is the preeclampsia and eclampsia, 41 patients (74.5%); the
      other causes are: the septic conditions: 6 patients (11%); the obstetrical
      hemorrhages: 4 patients (7.2%); the in uterofetal death: 3 patients (5.5%) and
      the post-cesarotomy: 1 patient (1.8%). 74.6% of the patients has been
      hemodialysed. The evolution has been characterized by the normal recuperation of
      the renal function is 48 patients (87.3%), a chronic renal failure in 2 patients
      (3.6%) and the death of 5 patients (mortality: 9.1%). The gravidic ARF is still a
      critical circumstances associated to a severe prognosis as well as in the woman
      and the fetus. So, the most effective measures are still the prevention and the
      managing of the obstetrical complications.

PMID- 11284468
TI  - New technology assists in meeting A.S.P.E.N. and A.S.H.P. safety guidelines to
      minimize total parenteral nutrition compounding errors.

PMID- 11284467
TI  - Intestinal adaptation: a new era.

PMID- 11284466
TI  - Effect of platelet-activating factor on gastrin release from cultured rabbit G
      cells.
AB  - Gastric infection with Helicobacter pylori is associated with hypergastrinemia.
      Platelet activating factor (PAF) is produced in H. pylori-infected mucosa. The
      effects of PAF on gastrin release from cultured antral rabbit G cells were
      examined. Rabbit antral G-cells were obtained by collagenase-EDTA digestion and
      enriched by centrifugal elutriation. After 40 hr in culture, gastrin release in
      response to PAF was assessed. PAF stimulated gastrin release in a dose-dependent
      manner. A maximal release of 67% above basal was seen with PAF at 100 nM. PAF
      also enhanced the gastrin release stimulated by forskolin and bombesin. PAF
      stimulated gastrin release was abolished by a PAF-receptor antagonist. Gastrin
      release stimulated by PAF was abolished by chelation of intra- or extracellular
      calcium or the L-type calcium channel inhibitor verapamil as well as by the
      protein kinase C inhibitor chelerythrine. Platelet-activating factor may
      contribute to the hypergastrinemia of H. pylori infection by stimulating gastrin
      release from G cells. PAF-stimulated gastrin release involves influx of
      extracellular calcium via L-type channels and activation of protein kinase C.

PMID- 11284469
TI  - Reliable bioelectrical impedance analysis estimate of fat-free mass in liver,
      lung, and heart transplant patients.
AB  - BACKGROUND: Bioelectrical impedance analysis (BIA) can be valuable in evaluating
      the fat-free (FFM) and fat masses (FM) in patients, provided that the BIA
      equation is valid in the subjects studied. The purpose of the clinical evaluation
      was to evaluate the applicability of a single BIA equation to predict FFM in pre-
      and posttransplant patients and to compare FFM and FM in transplant patients with
      healthy controls. METHODS: Pre- and posttransplant liver, lung, and heart
      patients (159 men, 86 women) were measured by two methods-50-kHz BIA-derived FFM
      (FFM(BIA)) by Xitron instrument and DXA-derived FFM (FFM(DXA)) by Hologic QDR
      4500 instrument-and compared with healthy controls (196 men, 129 women), aged 20
      to 79 years. RESULTS: The high correlation coefficient (r = .974), small bias
      (0.3 +/- 2.3 kg), and small SEE (2.3 kg) suggest that BIA using the GENEVA
      equation is able to predict FFM in pre- and posttransplant patients. The study
      shows that the lower weight seen in transplant men and women than in controls was
      due to lower FFM, which was partially offset by higher FM in men but not in
      women. Furthermore, the higher weights in posttransplant than in pretransplant
      patients were due to higher FM and % FM that was confirmed by lower FFM/FM ratio
      in posttransplant patients. CONCLUSIONS: Single 50-kHz frequency BIA permits
      measurement of FFM in pre- and posttransplant patients.

PMID- 11284470
TI  - Total parenteral nutrition decreases liver oxidative metabolism and antioxidant
      defenses in healthy rats: comparative effect of dietary olive and soybean oil.
AB  - BACKGROUND: Total parenteral nutrition (TPN) is used for critically ill patients
      undergoing surgery, after trauma, or during disease conditions that favor
      oxidative stress. We studied the effect of TPN on liver oxidative metabolism and
      antioxidant defenses in rats, and we compared the effect of soybean oil- and
      olive oil-based diets. METHODS: Seven-week-old rats (n = 28) were divided into
      four groups. Two experimental groups received a TPN solution containing soybean
      oil (TPN-S) or a mixture of olive/soybean oil, 80/20 (TPN-O), IV for 6 days.
      Orally fed animals received a solid diet including soybean oil (Oral-S) or
      olive/soybean oil, 80/20 (Oral-O). The following parameters were measured: DL
      alpha-tocopherol, vitamin A, malondialdehyde and thiobarbituric acid reactive
      substances (MDA-TBARS), and total radical-trapping antioxidant parameter (TRAP)
      in serum; DL-alpha-tocopherol, vitamin A, glutathione (GSH), and catalase (Cat)
      activity in liver homogenate; fatty acids from phospholipid, cytochrome P-450
      content, NADPH-cytochrome c2 reductase activity in liver microsomes; superoxide
      dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR),
      glutathione transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) in
      liver cytosol. RESULTS: The soybean or olive oil diets modified the liver
      microsomal fatty acid phospholipid composition, but the unsaturation index
      remained unchanged. TPN specifically increased the saturation of the membrane.
      The cytochrome P-450 level and the NADPH-cytochrome c2 reductase, SOD, Gpx, Cat,
      and GST activities were unchanged by soybean oil or olive oil diet but decreased
      receiving TPN. CONCLUSIONS: In rats, TPN decreased the liver oxidative metabolism
      and enzymatic antioxidant defenses. This may be related to saturation of the
      liver microsomal fatty acids.

PMID- 11284471
TI  - Liquid enteral diets induce bacterial translocation by increasing cecal flora
      without changing intestinal motility.
AB  - The aim of this study was to determine the contribution of intestinal motility
      and cecal bacterial overgrowth to liquid diet-induced bacterial translocation
      (BT). Three different commercially available liquid diets were offered to mice
      for 1 week. BT to the mesenteric lymph nodes (MLN), spleen, and liver were
      examined as well as cecal bacterial counts and populations, small bowel length
      and weight, and histopathologic changes in the ileal and jejunal mucosa. In
      addition, the effect of the various diets on intestinal motility was measured by
      the transit index of a charcoal mixture introduced into the stomach. The
      incidence of BT to the mesenteric lymph nodes was significantly and similarly
      increased (p < .05) in mice fed Vivonex (30%), Ensure (30%), and Osmolite (33%)
      compared with chow-fed controls (0%). Compared with chow-fed controls, all three
      liquid diets were associated with the development of cecal bacterial overgrowth
      (p < .01). There were no significant changes in the transit index for the three
      liquid diet groups compared with the chow-fed controls. BT to the MLN was induced
      by all three liquid diets tested, casting some doubts as to their role in
      preventing BT in clinical use. BT was associated with a statistically significant
      increase in cecal bacterial count but was not associated with gut motility
      changes in this model. In fact, no significant changes in intestinal motility
      were noted in all groups tested.

PMID- 11284472
TI  - Growth factors regulation of rabbit sodium-dependent neutral amino acid
      transporter ATB0 and oligopeptide transporter 1 mRNAs expression after
      enteretomy.
AB  - BACKGROUND: Sucessful intestinal adaptation after massive enterectomy is
      dependent on increased efficiency of nutrient transport. However, midgut
      resection (MGR) in rabbits induces an initial decrease in sodium-dependent brush
      border neutral amino acid transport, whereas parenteral epidermal growth factor
      (EGF) and growth hormone (GH) reverse this downregulation. We investigated
      intestinal amino acid transporter B0 (ATB0) and oligopeptide transporter 1 (PEPT
      1) mRNA expression after resection and in response to EGF and/or GH. METHODS:
      Rabbits underwent anesthesia alone (control) or proximal, midgut, and distal
      resections. Full-thickness intestine was harvested from all groups on
      postoperative day (POD) 7, and on POD 14 from control and MGR rabbits. A second
      group of MGR rabbits received EGF and/or GH for 7 days, beginning 7 days after
      resection. ATB0 and PEPT 1 mRNA levels were determined by Northern blot analysis.
      RESULTS: In control animals, ileal ATB0 mRNA abundance was three times higher
      than jejunal mRNA, whereas PEPT 1 mRNA expression was similar. By 7 and 14 days
      after MGR, jejunal ATB0 mRNA abundance was decreased by 50% vs control jejunum. A
      50% decrease in jejunal PEPT 1 message was delayed until 14 days after MGR.
      Treatment with EGF plus GH did not alter ATB0 mRNA expression but doubled PEPT 1
      mRNA in the jejunum. CONCLUSION: The site of resection, time postresection, and
      growth factors treatment differentially influence ATB0 and PEPT 1 mRNA
      expression. Enhanced sodium-dependent brush border neutral amino acid transport
      with GH plus EGF administration is independent of increased ATB0 mRNA expression
      in rabbit small intestine after enterectomy.

PMID- 11284474
TI  - Comparison of gastrointestinal tolerance to two enteral feeding protocols in
      critically ill patients: a prospective, randomized controlled trial.
AB  - BACKGROUND: The purpose of this study was to compare gastrointestinal tolerance
      to two enteral feeding protocols in critically ill patients. METHODS: A
      prospective, randomized controlled trial, that involved 96 consecutive patients
      expected to stay in the intensive care unit for > or =3 days and who had no
      contraindications to enteral feeding. The patients were randomized to either the
      current protocol (group I; gastric residual volume threshold, 150 mL, optional
      prokinetic) or proposed feeding protocol (group II; gastric residual volume
      threshold 250 mL, mandatory prokinetic). Gastrointestinal intolerance was
      recorded as episodes of high gastric residual volume, emesis, or diarrhea. The
      time to reach the goal rate of feeding and the percentage of nutritional
      requirements received during the study period were also recorded. RESULTS:
      Nineteen of 36 patients (19/36 = 0.53) in group I had one or more episodes of
      high gastric residual volume, compared with 10 of 44 patients (10/44 = 0.23) in
      group II (p < .005). There was no statistical difference between the two
      protocols with regards to emesis, diarrhea, or the total episodes of intolerance.
      The patients in group II reached their goal rates on average in 15 hours and
      received 76% of their nutritional requirements, compared with 22 hours and 70% in
      group I; however, these differences were not statistically significant.
      CONCLUSIONS: The incidence of enteral feeding intolerance was reduced by using a
      gastric residual volume of 250 mL along with the mandatory use of prokinetics.
      The study showed a trend of improved enteral nutrition provision and reduced the
      time to reach the goal rate in group II. These improvements support the adoption
      of the proposed feeding protocol for critically ill patients.

PMID- 11284473
TI  - Small bowel segment reversal induces intestinal hyperplasia but reduces whole
      body growth in massive bowel resected rats.
AB  - BACKGROUND: Surgical reversal of a small bowel segment has been proposed as a
      means to improve nutritional status in individuals with extensive bowel
      resection. However, clinical experience remains controversial. The aim of this
      study was to determine the effects of bowel segment reversal on intestinal
      adaptation and whole-body anabolism. METHODS: Male Wistar rats underwent a 70%
      small bowel resection with (REV) or without (CON) reversal of a 5-cm small bowel
      segment (5 cm distal to resected segment), or sham-operation (SHAM). After
      surgery (day 0), rats were fed with powdered diet from day 2 to day 12. Body
      weight, nitrogen balance, carcass compositions, and serum concentrations of
      albumin and insulin-like growth factor (IGF)-1 were determined to assess whole
      body anabolism. The composition and architecture of the small intestine were
      measured to assess the intestinal growth response. Serum concentrations of tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-6 were measured to assess the
      response of postoperative cytokines. RESULTS: Surgical reversal significantly
      increased the intestinal protein and DNA contents in the proximal segment
      compared with surgical resection. REV rats had a significantly slower rate of
      weight gain and lower serum levels of albumin and IGF-1, and had significantly
      greater levels of circulating white blood cells, blood urea nitrogen, and IL-6
      compared with CON and SHAM rats. There were no significant differences in serum
      concentrations of TNF-alpha and carcass percentages of water, protein, and fat
      among groups. CONCLUSIONS: Small bowel segment reversal stimulates jejunal
      hyperplasia but the surgical reversal induced-elevation in serum IL-6 may
      eliminate the whole-body anabolism in massive bowel-resected rats.

PMID- 11284475
TI  - On-off study of manganese administration to adult patients undergoing home
      parenteral nutrition: new indices of in vivo manganese level.
AB  - BACKGROUND: Recently, there have been reports that magnetic resonance imaging
      (MRI) reveals high-intensity T1-weighted images (HI) in the basal ganglia
      (especially in the globus pallidus) of patients receiving total parenteral
      nutrition (TPN). This finding is presumably due to excess administration of
      manganese. We investigated the reversibility and reproducibility of these changes
      by means of an on-off manganese administration study. We also investigated the
      temporal relationships between the intensity of T1-weighted images (MRI
      intensity) and the whole-blood and plasma manganese concentrations to evaluate
      the potential for the MRI intensity to serve as an index of the in vivo manganese
      level. METHODS: Eleven adult patients undergoing home parenteral nutrition
      received TPN solutions containing manganese (0 or 20 micromol/d) according to an
      on-off design. The whole-blood and plasma manganese concentrations were
      determined at the same time the brain MRI was performed. RESULTS: Both the whole
      blood manganese concentration and the MRI intensity in the globus pallidus
      changed in response to the administration and withdrawal of manganese. It took at
      least 5 months for HI to disappear when manganese was withdrawn, and this change
      was reversible and reproducible. The whole-blood manganese concentration showed
      strong correlations with both the MRI intensity and the T1 value (r = 0.7693, 
      0.7011). The MRI intensity and the T1 value showed a strong correlation (r = 
      0.9051). CONCLUSIONS: The whole-blood manganese concentration, the MRI intensity
      in the globus pallidus and the T1 value, an objective index of the MRI intensity,
      may be useful indices of the manganese level in the body.

PMID- 11284476
TI  - A new simple technique for the insertion of cuffed central venous catheters: an
      initial experience.
AB  - BACKGROUND: Although tunneled polyurethane catheters with polyester cuffs are
      useful when prolonged central venous access is necessary but their insertion
      still remains challenging at times. We report the first study of a new cuffed
      polyurethane catheter (Seldicuff) that can be easily inserted using the Seldinger
      technique without the need of a vein dilator and that incorporates a tunneling
      needle onto the catheter. A Seldicuff catheter was placed in 15 patients (mean
      age: 53 +/- 11 years) who required prolonged parenteral nutrition. All catheters
      were inserted into the right subclavian vein. The procedure lasted 6.4 +/- 0.8
      minutes and no complication directly related to catheter placement was noted.
      Catheters remained in position for a mean duration of 103 days (range, 58 to 220
      days). During this period, no infectious or mechanical complications were
      observed. CONCLUSION: These results demonstrate that placement of this novel
      cuffed catheter is as simple as inserting a conventional central venous catheter.

PMID- 11284477
TI  - Manganese intoxication during intermittent parenteral nutrition: report of two
      cases.
AB  - BACKGROUND AND METHODS: The administration of trace elements is thought to be
      needed in patients receiving long-term parenteral nutrition. Recently, manganese
      intoxication or deposition was documented in such patients. We report two cases
      of manganese intoxication during intermittent parenteral nutrition including
      manganese. Manganese had been administered for 4 years at a frequency of one or
      two times per week in one case and for 5 years at a frequency of one or two times
      per month in the other case. Both cases showed mild symptoms with headache and
      dizziness. One case had mild hepatic dysfunction and the other did not. The whole
      blood manganese level increased in one case, but not in the other case. T1
      weighted magnetic resonance images revealed symmetrical high-intensity areas in
      basal ganglia and thalamus in both cases. After the administration of manganese
      was stopped, these symptoms all disappeared and the magnetic resonance images
      abnormalities gradually improved in both patients. Mild long-term manganese
      intoxication is thus considered to occur regardless of the frequency of using a
      manganese supplement. CONCLUSIONS: Patients should be carefully monitored when
      receiving long-term parenteral nutrition including manganese, even when the
      manganese dose is small and the frequency of receiving a manganese supplement is
      low.

PMID- 11284478
TI  - Myopia and level of education.
AB  - PURPOSE: To find out whether the development of myopia is related to the level of
      education. MATERIALS AND METHODS: From two big ophthalmic outpatient clinics in
      Jordan, 968 subjects (between the age of 24 and 45 years) were included in this
      study. A subject was considered myopic if at least one eye had a spherical
      equivalent refractive error of at least -0.75 diopter. The subjects were divided
      into two groups: the educated group was those who had finished at least 12 years
      of education and the non-educated which included those with maximum of six years
      of education. There were 468 men and 500 women. RESULTS: The frequency of myopia
      was higher in the educated group in both men and women. A significant
      relationship was found between the level of education and myopia in the whole
      study group (p<0.0001). CONCLUSIONS: This study had too few subjects to draw
      general conclusions, but within the study group there was a significant
      relationship between the level of education and the development of myopia.

PMID- 11284479
TI  - Ocular ferning during the menstrual cycle in healthy women.
AB  - PURPOSE: The aim of the study is to investigate whether tear ferning patterns
      change during different phases of the menstrual cycle. METHODS: The tear ferning
      test was performed on twelve normal women of childbearing age at three day
      intervals throughout one complete menstrual cycle. Serum hormone levels
      (progesterone, estrogen, testosterone) were measured. RESULTS: Eight women showed
      type I ferning, and the other four had type II ferning initially. These patterns
      did not change during the menstrual cycle. Serum hormone levels were all in the
      normal range. Since no change in ferning pattern was detected during the
      menstrual cycle, the ferning test can be done at any time in women. CONCLUSIONS:
      This study showed no effect of different menstrual cycle phases on tear ferning
      patterns.

PMID- 11284480
TI  - High performance liquid chromatography analysis of tear protein patterns in
      diabetic and non-diabetic dry-eye patients.
AB  - PURPOSE: To analyze and compare the high performance liquid chromatography (HPLC)
      runs of tear proteins from diabetic (DIDRY) and non-diabetic (DRY) dry-eye
      patients, and healthy subjects (CTRL). The patterns were analyzed using
      multivariate statistical methods. METHODS: Tears (total 56 eyes: CTRL: n=16,
      DIDRY: n=21, and DRY: n=19) were analyzed by HPLC, using a size-exclusion column
      with an eluent of 0.5 M sodium phosphate buffer. The patients were primarily
      grouped according to the results of the basic secretory test (BST) in combination
      with subjective symptoms such as burning, foreign body sensations, tearing, and
      "dryness" of the eyes. Patients with BST values < or = 10 mm/5 min plus two
      subjective symptoms were grouped as dry-eye patients. Before statistical
      analysis, each HPLC run was quantitatively analyzed using ScanPacK software
      (ScanPacK, Gottingen, Germany), and a data set was created from each HPLC run.
      The data were then analyzed by multivariate analysis of discriminance. RESULTS:
      The HPLC patterns of CTRL, DIDRY and DRY were significantly different (Wilks'
      lambda: 0.0209; p<0.01). The area of the sigA peak was significantly smaller
      (p<0.05) in dry-eye tears than controls. There was a good correlation between the
      extent of separation in the multivariate analysis and the BST value (r = -0.71).
      Classification of all samples resulted in 98% correct assignments. CONCLUSIONS:
      The analysis of HPLC patterns and subsequent statistical evaluation are useful
      for the detection of dry eyes. The HPLC method and the statistical routines
      described allow a shorter analysis time than electrophoresis. HPLC analysis in
      combination with statistical analysis can be used as a diagnostic tool for the
      detection of dry eyes, and also improves the quality of analysis of disease
      associated tear proteins in clinical research.

PMID- 11284481
TI  - Nasolacrimal polyurethane stent placement: preliminary results.
AB  - PURPOSE: To present our initial results in the treatment of nasolacrimal
      obstruction by placing a polyurethane stent. METHODS: 74 nasolacrimal stents were
      implanted under fluoroscopic guidance in obstructed nasolacrimal systems of 64
      patients. Dacryocystography and CT were used to verify the position and patency
      of the stents. Mean follow-up was 15 months. Clinical examinations were done at
      the first week, first month, third month and sixth month after stent placement.
      RESULTS: Polyurethane stents were successfully inserted and permeable in 59
      patients (92.1%), but could not be inserted in 5 patients (7.8%). Epiphora was
      solved and permeable in 53 cases (82.8%), it was not permeable but asymptomatic
      in 2 cases (3.1%), and was not permeable but symptomatic in 4 (6.2%). In 5 cases
      (7.8%) stents remained permeable although patients complained of epiphora.
      CONCLUSIONS: Polyurethane stent placement is a non-invasive technique that can
      replace dacryocystorhinostomy, giving better results and tolerance.

PMID- 11284482
TI  - Does surgical technique influence cataract surgery contamination?
AB  - PURPOSE: To compare cataract surgery contamination rates in large-incision
      extracapsular cataract extraction (ECCE) and phacoemulsification (PE), we studied
      65 cases prospectively. METHODS: Thirty-five cases were operated by large
      incision ECCE (Group I) and 30 by PE (Group II). Conjunctival swab cultures were
      taken immediately before surgery and anterior chamber aspirate was taken for
      culture upon completion of surgery for each case. RESULTS: Anterior chamber
      cultures were positive in 22.8% of the cases in group I and 23% in Group II.
      Frequencies of contamination in each group were no different (x2: 0.22, p>0.05).
      When the contaminations were evaluated in relation to operating time,
      prolongation of the operating time raised the contamination rate in Group I
      (p<0.05) but not in Group II (p>0.05). Silicone and PMMA intraocular lenses (IOL)
      were tested to see whether they had any additional risk of contamination. The
      frequencies of contaminated silicone IOL implanted cases (6/26) and contaminated
      PMMA IOL implanted cases (8/39) were similar (x2: 0.36, p>0. 05). CONCLUSIONS:
      Although the architecture of the incision and irrigation dynamics provided an
      advantage to the PE technique as the operating time became longer, routine PE was
      not superior to classical ECCE with respect to contamination when performed in
      the same circumstances. Prolonging the operating time raised the contamination
      rate in classical ECCE.

PMID- 11284484
TI  - Increase of free oxygen radicals in aqueous humour induced by selective Nd:YAG
      laser trabeculoplasty in the rabbit.
AB  - PURPOSE: To investigate the impact of selective Nd:YAG laser trabeculoplasty on
      free oxygen radicals and antioxidant enzymes of the aqueous humour in the rabbit.
      METHODS: One eye of 18 rabbits was subjected to 360 degrees selective laser
      trabeculoplasty (LT) with a frequency-doubled Nd:YAG laser (532 nm). The anterior
      chamber aqueous humour was aspirated 3, 12 hours and 1, 3, 7, 10 days after
      treatment. Lipid peroxide (LPO) and glutathione S transferase (GST) levels and
      superoxide dismutase (SOD) activities of aqueous humour were measured. RESULTS:
      Concentrations of LPO in the aqueous humour of the treated eyes were
      significantly higher than the untreated eyes until the 7th day. Aqueous SOD
      activity significantly decreased 3 hours after LT and remained low until day 7.
      Aqueous GST levels were significantly decreased between 12 hours and 7 days after
      the LT. CONCLUSIONS: Selective LT was followed by an immediate increase in the
      aqueous humour LPO concentration and decreases of SOD and GST in the rabbit,
      probably due to photovaporization and photodisruption caused by the frequency
      doubled Nd:YAG laser. The increased aqueous LPO levels suggest that free oxygen
      radicals are formed in the pigmented trabecular meshwork during LT, and may be
      responsible for the inflammatory complications of this procedure.

PMID- 11284483
TI  - The effects of beta-blockers on ocular blood flow in patients with primary open
      angle glaucoma: a color Doppler imaging study.
AB  - PURPOSE: To evaluate the effects of four commonly used beta-blockers on ocular
      blood flow in patients with primary open angle glaucoma (POAG). METHODS: Eighty
      eyes of 40 subjects with POAG were included in the study. Subjects were randomly
      divided into four groups given timolol maleate 0.50%, betaxolol HCl 0.50%,
      carteolol 1% or levobunolol 0.50% drops, applied twice daily (one drug to each
      group). Before beginning the treatment and at the end of the first month ocular
      blood flow velocity was measured using the color Doppler imaging (CDI) method. In
      the ophthalmic artery (OA), central retinal artery (CRA) and temporal posterior
      ciliary artery (TPCA) the peak systolic (PS) and end-diastolic (ED) blood flow
      velocities were measured and resistive index (RI) values were calculated. The
      results within each group were analysed using the matched paired student's t
      test. The data between groups was compared with one-way analysis of variance
      (ANOVA) and Tukey-Kramer multiple comparison tests. RESULTS: The timolol group
      showed a significant increase in RI values of TPCA. In the betaxolol group RI
      decreased significantly in CRA and TPCA, whereas in the carteolol group there was
      a significant decrease only in CRA. In the levobunolol group there was no change
      in any artery. CONCLUSIONS. Betaxolol seemed to have a greater vasodilator effect
      than carteolol, and levobunolol had no effect on the retinal and choroidal
      vasculature. Timolol may have some vasoconstrictive effect in the ciliary
      vasculature.

PMID- 11284485
TI  - Uveitis in HIV-infected patients.
AB  - PURPOSE: To determine the prevalence of HIV infection and to find out the
      possible causes (associated conditions) of uveitis in HIV-infected patients.
      METHODS: We retrospectively analyzed the data of 581 patients with uveitis
      diagnosed over an 11-year period. All patients received a routine eye examination
      and most of them a general examination as well as complementary tests. RESULTS:
      The prevalence of HIV infection was 14.3% (89 patients). Anterior uveitis (62%)
      was the most frequent form, followed by posterior uveitis (22%), panuveitis (12%)
      and intermediate uveitis (4%). Associated conditions or causes were found in 88%
      of these 89 patients, the most frequent being Herpes zoster ophthalmicus (43%),
      tuberculosis (16%), CMV infection (12%) and toxoplasmosis (10%). CONCLUSIONS: In
      HIV-infected patients uveitis is frequently associated with opportunistic
      infections.

PMID- 11284486
TI  - Asteroid hyalosis.
AB  - PURPOSE: This study evaluated ocular and systemic diseases in patients with
      asteroid hyalosis and compared axial lengths of asteroid hyalosis patients with
      the normal population. METHODS: The examination of 26 patients with asteroid
      hyalosis consisted of complete history, complete ocular examination, blood
      pressure and laboratory studies in order to detect systemic diseases, A and B
      scan ultrasonography to measure axial lengths and to detect posterior vitreous
      detachment. RESULTS: All patients had unilateral asteroid hyalosis; 10 (38.5%)
      were symptomatic. Eight patients (20.5%) had type II diabetes mellitus, 13
      (33.3%) patients had systemic arterial hypertension and 7 (18%) had
      atherosclerotic heart disease; 5 (12.8%) had hyperlipidemia and 6 (15.4%) had
      hypercholesterolemia. Posterior vitreous detachment was found in 3 (11.5%)
      patients with asteroid hyalosis, and 6 patients in the control group (23.1%) had
      posterior vitreous detachment (p<0.01). In patients with asteroid hyalosis, the
      mean axial length difference between two eyes was 0.32 +/- 0.06, against 0. 10 +/
      0.02 in the control group (p<0.01). CONCLUSION: Asteroid hyalosis may be found
      together with systemic diseases and such patients must be evaluated
      systematically for diabetes mellitus, hypertension and hyperlipidemia. Asteroid
      hyalosis can also cause artefactual lowering of axial length measurement, leading
      to significant error in calculations of intraocular lens power. This must be kept
      in mind before cataract surgery.

PMID- 11284488
TI  - Lipoprotein (a) in Behcet's disease as an indicator of disease activity and in
      thrombotic complications.
AB  - PURPOSE: To evaluate the utility of plasma concentrations of lipoprotein (a)
      (Lp(a)) as an indicator of disease activity in Behcet's disease and to
      investigate its role in thrombotic complications of this disease. METHODS: 30
      patients (19 male, 11 female) with Behcet's disease (8 active, 22 inactive) were
      enrolled in the study group and 30 healthy individuals (16 male, 14 female) in
      the control group. Seven of the inactive Behcet's disease patients had a history
      of thrombotic complications. The disease activity was evaluated by clinical
      manifestations (oral aphthous lesions, genital ulcerations, uveitis and
      vasculitis) and laboratory investigations (leucocyte count, lipoprotein (a), C
      reactive protein (CRP), complement 3 (C3) and complement 4 (C4) concentrations).
      RESULTS: Plasma Lp(a) and other acute phase reactant concentrations were
      significantly higher in the study group than in the controls (p < 0.01). These
      concentrations were also higher during the active period of the disease than
      during the inactive phase (p < 0.01). Lp(a) concentrations were significantly
      correlated with concentrations of other acute phase reactants. There was no
      difference between the groups with and without thrombotic complications for any
      of these measurements. CONCLUSIONS. Plasma levels of Lp(a) might be an indicator
      of disease activity in Behcet's disease. There is no correlation between Lp(a)
      levels and thrombotic sequela in inactive Behcet's disease. However, further
      studies are needed on the thrombogenic role of Lp(a) during the active phase of
      thrombophlebitis, and in larger series.

PMID- 11284487
TI  - Large bilateral lateral rectus recession in large angle divergence excess
      exotropia.
AB  - PURPOSE: Classic teaching suggests that surgery for intermittent exotropia should
      be based on distance/near differences. True divergence excess exotropia should be
      treated with symmetric lateral rectus recession. The aim of this study was to
      investigate the effect of large bilateral lateral rectus (LR) recession in large
      angle intermittent exotropia. METHODS: Thirty-three consecutive patients with
      large-angle divergence excess exotropia ranging from 50 to 65 (mean 56.7 +/- 6.3)
      prism diopters were treated with 8.0 to 9.5 mm (mean 8.8 +/- 0.7 mm) recession of
      both LR muscles. RESULTS: Successful alignment was achieved in 25 cases (76%)
      while residual exotropia was seen in eight patients (24%) within the limit of 15
      prism diopters. Mean follow-up time was 28.5 +/- 8.4 (range 13 to 38) months.
      Abduction deficit due to this procedure was not seen in any case. CONCLUSIONS: We
      conclude that large bilateral LR recession is an appropriate surgical method for
      large-angle divergence excess exotropia.

PMID- 11284489
TI  - Fibrinolytic response to retinal detachment surgery under general or local
      anesthesia.
AB  - PURPOSE: To evaluate perioperative changes in fibrinolysis in patients undergoing
      retinal detachment surgery under general or local anesthesia. PATIENTS:
      Prospective study of 81 patients (43 male, 38 female), aged from 15 to 82 (mean
      50.7 SD = 17.8) years, undergoing retinal detachment surgery (encirclement with
      scleral buckling) under general anesthesia (group A), and 14 patients (6 male, 8
      female) aged from 15 to 78 (mean 52.9, SD =19.8) years, operated under local
      anesthesia (group B). Excluded were patients with venous or arterial disease or
      other factors that could change the parameters investigated. METHODS: Blood was
      sampled from a cubital vein one day before surgery, immediately after induction
      of anesthesia but before surgery, immediately after completion of the operation
      but before the termination of anesthesia and after the operation (on days 1 and
      4). In patients' citrated plasma, tissue plasminogen activator antigen (t-PA-Ag),
      plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and activity (PAI-1),
      fibrin-fibrinogen degradation products (FDP) and euglobulin lysis time (ELT) were
      measured. RESULTS. The pattern of changes in perioperative fibrinolytic activity
      was similar in both groups. Intraoperative levels of FDP were significantly
      higher and ELT shorter than preoperatively. In both groups t-PA Ag concentration
      was significantly increased on the first postoperative day. There were no changes
      in PAI-1 in both groups. Postoperatively, the FDP concentration was reduced and
      ELT prolonged. CONCLUSIONS: Retinal detachment surgery induces intraoperative
      activation of fibrinolysis in the systemic circulation regardless of the type of
      anesthesia.

PMID- 11284490
TI  - Keratoconus and Fuchs' heterochromic iridocyclitis: a coincidence or a defect
      during embryogenesis?
AB  - PURPOSE: We aimed to discuss the possible role of developmental embryologic
      factors in neural crest cells in the aetiology of keratoconus and Fuchs'
      heterochromic iridocyclitis by presenting this case. CASE REPORT: We diagnosed
      bilateral keratoconus and unilateral Fuchs' heterochromic iridocyclitis in a 19
      year old women complaining of progressively blurring vision in her left eye. We
      also examined most of her first and second degree relatives. One niece had FHI in
      addition to a choroidal nevus in the inferior temporal quadrant of her left eye.
      DISCUSSION: Regarding the common embryological origins of iris stroma, uveal
      melanocytes and corneal stroma, it might be worth considering that the
      combination of FHI and keratoconus is not coincidental. A role of embryologic
      factors in neural crest cells in the etiology of both diseases cannot be
      excluded.

PMID- 11284491
TI  - Bilateral orbital hemorrhage induced by labor.
AB  - We describe a woman in whom bilateral orbital hemorrhage occurred during labor.
      She developed sudden proptosis and complete loss of vision bilaterally. After a
      stillbirth, she underwent total hysterectomy because of atonic uterus and
      postpartum hemorrhage. The location of the hematomas was confirmed by magnetic
      resonance imaging. Clinical resolution occurred in one month but both eyes
      remained blind. Fundoscopy revealed bilateral atrophy of the optic discs.

PMID- 11284492
TI  - Chondroid syringomas of the eyelid: two cases.
AB  - PURPOSE: We report two new cases of chondroid syringoma (CS) of the eyelid. Until
      1961, this entity was known as pleomorphic adenoma or benign mixed tumour of the
      skin of salivary glands type. This tumour occurs most commonly in the head and
      neck regions. CASE REPORTS: We describe two cases of CS with rapid growth, in the
      upper right eyelid, with no relation with the palpebral lobe of the lacrimal
      gland. RESULTS. Treatment consists of wide local surgical excision with its
      capsule, in its entirety. CONCLUSIONS: These tumours of the ocular adnexa are
      exceedingly rare. Malignant transformation is possible.

PMID- 11284493
TI  - Bilateral myopia following blunt trauma to one eye.
AB  - PURPOSE: To evaluate bilateral myopia following blunt trauma to one eye. CASE
      REPORT: Traumatic myopia is a rare transient situation which may be seen in the
      injured eye or both eyes after blunt ocular trauma. We examined one case with
      transient myopia in the left eye which had been exposed to a blunt ocular injury.
      Myopia was also observed in the right eye 12 hours after the trauma. The right
      eye and left eye had reverted to emmetropia respectively two and six weeks after
      trauma. DISCUSSION: The myopia may have been due to ciliary spasm arising from
      stimulation of the efferent autonomic system in the right eye and ciliary body
      edema in the left eye. CONCLUSIONS: To our knowledge, this is the first reported
      case developing bilateral transient myopia after the blunt trauma to only one
      eye.

PMID- 11284494
TI  - Treatment of multiple evanescent white dot syndrome with cyclosporine.
AB  - PURPOSE: To report the seven-year follow-up of a patient with multiple evanescent
      white-dot syndrome (MEWDS). METHODS:  CASE REPORT: A 46-year-old woman presented
      recurrent episodes of bilateral MEWDS. RESULTS: During the seven-year follow-up
      there were nine episodes of MEWDS. After four bouts in the first two,
      cyclosporine therapy was started. During two years of treatment there were no
      recurrences except when the dose was reduced or discontinued. CONCLUSIONS: The
      etiology of MEWDS is still unknown but the absence of new episodes during
      cyclosporine treatment and the recurrence immediately after decreasing or
      discontinuing the drug suggests an autoimmune origin, with the involvement of
      cellular immunity in the pathogenic process.

PMID- 11284495
TI  - Exudative retinal detachment following grid laser photocoagulation in a patient
      with hemiretinal vein occlusion.
AB  - PURPOSE: To report a patient with unilateral hemiretinal vein occlusion and
      macular edema who developed exudative macular detachment after grid laser
      application. METHODS: Clinical examinations, fundus photography and fluorescein
      angiography. RESULTS: Severe macular edema and exudation. CONCLUSIONS: This case
      illustrates a previously unreported complication of grid laser application for
      macular edema in retinal vein occlusion.

PMID- 11284496
TI  - The eye in cystic fibrosis.
AB  - PURPOSE: To investigate modifications of ocular surface and lens transparency in
      patients with cystic fibrosis in relation to the stage of digestive
      insufficiency. METHODS: Forty consecutive patients with cystic fibrosis and 24
      age- and sex-matched healthy volunteers were examined. The tear tests (Schirmer's
      basic test, tear film break-up time) and conjunctival exfoliative cytology (CC)
      were used to study the ocular surface. The lens transparency was measured with
      the Opacity Lens Meter 701 (OLM 701, Interzeag AG, Switzerland). Digestive
      insufficiency was evaluated by the steatocrit method. RESULTS: Significant
      changes in conjunctival cytology and lens opacity, and abnormal tear tests were
      detected in CF patients; the alterations were more pronounced in patients with
      severe digestive insufficiency. CONCLUSIONS: Cystic fibrosis patients present
      ocular surface abnormalities and lens transparency modifications and their
      severity is related to the digestive insufficiency. Simple, rapid and non
      invasive tear tests and cytological procedures might be used as additional tests
      for assessing the severity of cystic fibrosis.

PMID- 11284497
TI  - Bilateral glaucomatous optic neuropathy in Takayasu's disease without cervical
      arterial stenosis.
AB  - PURPOSE: Although significant decrease in retinal perfusion is usually not
      observed before all of the cervical arteries became markedly narrowed in patients
      with Takayasu's disease (TD), we present bilateral glaucomatous optic neuropathy
      in a patient with TD without any cervical arterial stenosis. METHODS:
      Ophthalmoscopic examination disclosed glaucomatous optic neuropathy in both eyes
      with 7/10-cup/disc ratio in the right eye and 9/10 in the left eye. Left
      subclavian selective arteriographic examination demonstrated segmental high-grade
      stenosis, namely 90 percent stenosis in the mid portion of the left subclavian
      artery. Arteriography, digital subtraction angiography (DSA), magnetic resonance
      angiography (MRA) and color Doppler sonography revealed patent cervical, carotid
      interna, ophthalmic, retinal and posterior ciliary arteries. RESULTS: Patient was
      followed up for 48 months with frequent intervals and there was no deterioration
      of visual acuity, visual field and optic neuropathy without any antiglaucomatous
      treatment. CONCLUSIONS: Although it is a known fact that classical ophthalmic
      manifestations of the TD occur only when major cervical arteries are occluded, no
      occlusion was observed in this patient with bilateral optic atrophy. The optic
      nerve damage is caused by various factors, but these factors require much
      elucidation before the optic neuropathy can be understood.

PMID- 11284498
TI  - Isolated ocular ischemic syndrome with no cerebral involvement in common carotid
      artery occlusion.
AB  - PURPOSE: The ocular ischemic syndrome (OIS) is sometimes a complication of common
      carotid artery (CCA) occlusion causing complete interruption of blood flow
      through both the internal and external carotid arteries we investigated a single
      case of an isolated OIS that remained undiagnosed for two years, because the
      underlying CCA pathology caused no cerebral involvement. CASE REPORT: A 57-year
      old man presented with subacute painful visual loss in the right eye in a setting
      of hypertension, smoking and coronary artery disease. RESULTS. Neurological
      examination, a brain CT and MRI scan were all normal. Extensive laboratory work
      up excluded small artery disease, inflammatory arteritis or cardiac causes of
      retinal embolism. Ophthalmologic evaluation and fluorescein angiography gave
      findings consistent with OIS, while vascular ultrasound evaluation and aortic
      arch angiography verified right CCA occlusion accompanied by an extensive
      collateral network. CONCLUSIONS: Had this patient been referred sooner for a
      simple carotid artery work-up, both the CCA occlusion and the OIS could probably
      had been prevented.

PMID- 11284499
TI  - An improved synthesis of the saponin, polyphyllin D.
AB  - Polyphyllin D, namely diosgenyl alpha-L-rhamnopyranosyl-(1 --> 2)- [(alpha-L
      arabinofuranosyl)-(1 --> 4)]-[beta-D-glucopyranoside, was synthesized from
      diosgenyl-beta-D-glucopyranoside in four steps and in 30% overall yield, taking
      advantage of regioselective pivaloylation and alpha-L-rhamnopyranosylation
      reactions.

PMID- 11284500
TI  - A rapid method for the separation and analysis of carrageenan oligosaccharides
      released by iota- and kappa -carrageenase.
AB  - Based on the improved performances in speed of chromatographic separation on
      Superdex-type materials (Pharmacia) compared to conventional media such as
      Sephadex and Bio Gel-type, a rapid size-exclusion chromatography (SEC) method was
      developed for the separation and analysis of carrageenan oligosaccharides. It was
      used to evaluate the elution profiles of hydrolysates produced by carrageenases
      specific for kappa- and iota-carrageenans. Oligosaccharide peaks ranging from di-
      to dodeca-saccharides were obtained in about 20 min on an analytical scale,
      whereas preparative runs were completed in a few hours. The method may also be
      used to monitor polysaccharide degradation.

PMID- 11284501
TI  - Inhibition of beta-glycosidases by acarbose analogues containing cellobiose and
      lactose structures.
AB  - Acarbose analogues, containing cellobiose and lactose structures, were prepared
      by reaction of the two disaccharides with acarbose and Bacillus
      stearothermophilus maltogenic amylase. The kinetics for the inhibition by the two
      analogues was studied for beta-glucosidase, beta-galactosidase, cyclomaltodextrin
      glucanosyltransferase (CGTase), and alpha-glucosidase. Both analogues were potent
      competitive inhibitors for beta-glucosidase, with K(I) values in the range of
      0.04-2.44 microM, and the lactose analogues were good uncompetitive inhibitors
      for beta-galactosidase, with K(I) values in the range of 159-415 microM, while
      acarbose was not an inhibitor for either enzyme at 10 and 5 mM, respectively.
      Both analogues were also potent mixed inhibitors for CGTase, with K(I) values in
      the range of 0.1-9.3 microM. The lactose analogue was a 6.4-fold better
      competitive inhibitor for alpha-glucosidase than was acarbose.

PMID- 11284502
TI  - Purification and molecular structure of two digalactosyl D-chiro-inositols and
      two trigalactosyl D-chiro-inositols from buckwheat seeds.
AB  - Two digalactosyl D-chiro-inositols and two trigalactosyl D-chiro-inositols,
      members of the fagopyritol A series and fagopyritol B series, were isolated from
      buckwheat (Fagopyrum esculentum Moench) seeds. Structures of the first three were
      determined by 1H and 13C NMR. Fagopyritol B2 is alpha-D-galactopyranosyl-(1-->6)
      alpha-D-galactopyranosyl-(1-->2) -1D-chiro-inositol, and fagopyritol A2 is alpha
      D-galactopyranosyl-(1-->6)-alpha-D-galactopyranosyl-(1-->3)- 1D-chiro-inositol.
      Fagopyritol A3, a trigalactosyl D-chiro-inositol, is alpha-D-galactopyranosyl-(1-
      >6)-alpha-D-galactopyranosyl-(1 -->6) -alpha-D-galactopyranosyl-(1-->3)- 1 D
      chiro-inositol. From analysis of hydrolysis products, the second trigalactosyl D
      chiro-inositol, fagopyritol B3, isalpha-D-galactopyranosyl-(1-->6)-alpha-D
      galactopyranosyl-(1-->6) -alpha-D-galactopyranosyl-(1-->2)-1D-chiro-inositol.

PMID- 11284503
TI  - DL-Galactan hybrids and agarans from gametophytes of the red seaweed gymnogongrus
      torulosus.
AB  - Seaweeds from the genus Gymnogongrus are known to be carrageenophytes;
      nevertheless, fractionation techniques used previously for the separation of gel
      forming and 'soluble' carrageenans, applied to the galactans of Gymnogongrus
      torulosus together with enantiomeric analysis of the sugar components and (when
      possible) of the structural units, suggested that the system of galactans
      biosynthesized by the seaweed was formed by DL-galactan hybrids having major
      amounts of carrageenan-type or agaran-type chains, with minor quantities of
      agarans with unusual structural details.

PMID- 11284504
TI  - Concepts for improved regioselective placement of O-sulfo, N-sulfo, N-acetyl, and
      N-carboxymethyl groups in chitosan derivatives.
AB  - In the present paper a new strategy has been studied to introduce solely or in
      combination N-sulfo, O-sulfo, N-acetyl, and N-carboxymethyl groups into chitosan
      with highest possible regioselectivity and completeness and defined distribution
      along the polymer chain. The aim was to generate compounds having lowest toxicity
      for determining the pharmacological structure function relationships among
      different backbone structures and differently arranged functional groups compared
      to those of heparin and heparan sulfate. The water-soluble starting material,
      chitosan, with a degree of acetylation (DA) of 0.14 and a molecular weight of 29
      kD, allows one to apply most of the known reactions of chitosan as well as some
      reactions of heparin chemistry successfully and with improved regioselectivity
      and completeness. On the other hand, a number of these reactions were not
      successful by application to water-soluble high-molecular-weight chitosan (DA
      0.45 and 150 kD). The starting material showed statistical N-acetyl (N-Ac)
      distribution along the polymer chain according to the rules of Bernoulli, with
      highest abundance of the GlcNAc-GlcNAc diad along with a lower abundance of
      triads, tetrads, and pentads. The space between the N-Ac groups was filled up in
      homogeneous reactions by N-sulfo and/or N-carboxymethyl groups, which also
      resulted in a Bernoulli statistical distribution. The N-substitution reaction
      showed highest regioselectivity and completeness with up to three combined
      different functional groups. The regioselectivity of the 3-O-sulfo groups was
      improved by regioselective 6-desulfation of nearly completely sulfated 3,6-di-O
      sulfochitosan. By means of desulfation reactions, all of the possible
      intermediate sulfated products are possible. 6-O-Sulfo groups can also be
      introduced with highest regioselectivity and completeness, and a number of
      partially 6-desulfated products are possible.

PMID- 11284505
TI  - Pyruvated galactose and oligosaccharides from Erwinia chrysanthemi Ech6
      extracellular polysaccharide.
AB  - The acidic extracellular polysaccharide of Ech6 was depolymerized by fuming HCl.
      The pyruvated sugars were isolated and characterized by methods that included a
      combination of low-pressure gel-filtration and high-pH anion-exchange
      chromatographies, methylation linkage analyses, mass (GC-MS and MALDI-TOF MS) and
      1H NMR (1D and 2D) spectroscopies. The following pyruvated sugars were obtained:
      4,6-O-(1-carboxyethylidene)-D-Galp; 4,6-O-(1-carboxyethylidene)- alpha-D-Galp-(1-
      >4)-beta-D-GlcAp-(1-->3)-D-Galp; 4,6-O-(1-carboxyethylidene)-alpha-D-Galp-(1-->4)
      alpha-D-GlcAp- (1-->3)-alpha-D-Galp-(1-->3)-L-Fucp; 4,6-O-(1-carboxyethylidene)
      alpha-D-Galp-(1-->4)-beta-D-GlcAp-(1-->3) -alpha-D-Galp-(1-->3)-L-[beta-D-Glcp-(1
      ->4)]-Fucp. These oligosaccharides present potential haptenes for the development
      of specific antibodies and confirm the partial structure proposed previously for
      the extracellular polysaccharide from Erwinia chrysanthemi Ech6 [Yang, B. Y.;
      Gray, J. S. S.; Montgomery, R. Int. J. Biol. Macromol., 1994, 16, 306-312].

PMID- 11284506
TI  - Structural revision of isovalertatins M03, M13, and M23 isolated from the culture
      of Streptomyces luteogriseus.
AB  - Three aminooligosaccharides, isovalertatins M03 (1), M13 (2), and M23 (3) were
      isolated and purified from the culture filtrate of Streptomyces luteogriseus.
      Their physicochemical properties, liquid chromatographic behavior, and
      spectroscopic data were in full accordance with the reported compounds [Xu, Q.;
      Wang, Q.; Lu, D. CN Patent 1100756, 1995; Chem. Abstr. 1995, 123, 110278n], but
      their structures were reinvestigated and revised by spectroscopic methods,
      including ESI multistage mass spectrometry and 2-dimensional NMR techniques.

PMID- 11284507
TI  - Synthesis of pyrrolo[2,1-f][1,2,4]triazine C-nucleosides. Isosteres of
      sangivamycin, tubercidin, and toyocamycin.
AB  - Syntheses of pyrrolo[2,1-f][1,2,4]triazine C-nucleosides are reported. Treatment
      of pyranulose glycoside with aminoguanidine in acetic acid gave the corresponding
      semicarbazone in 96% yield. The ring transformation of the semicarbazone in
      dioxane afforded a 51% yield of 2-amino-7-(2,3,5-tri-O-benzoyl-beta-D
      ribofuranosyl)pyrrolo[2,1-f]-[1,2,4]triazine. Vilsmeier formylation of the
      pyrrolotriazine gave the major product, 5-formylpyrrolo[2,1-f][1,2,4]triazine, in
      69% yield. The aldehyde was treated with hydroxylamine hydrochloride in methanol
      to give aldoximes. Dehydration of aldoxime with trifluoromethanesulfonic
      anhydride and triethylamine in dichloromethane afforded 5-cyanopyrrolo[2,1
      f][1,2,4]triazine in 44% yield. Conversion of the nitrile to the deprotected
      amide, 2-amino-7-(beta-D-ribofuranosyl)pyrrolo[2,1-f][1,2,4]triazine-5
      carboxamide, was accomplished in 96% yield on treatment with 30% H2O2 in ethanol
      for 1 day at room temperature. Debenzoylation with sodium hydroxide solution
      produced deprotected C-nucleosides.

PMID- 11284508
TI  - Synthesis of isotopically labeled D-[1'-13C]ribonucleoside phosphoramidites.
AB  - The preparation of fully protected labeled diisopropylamino-beta-cyanoethyl-[1'
      13C]ribonucleoside phosphoramidites with regioisomeric purity is described. We
      demonstrated in this paper that a regioselective 2'-O-silylation, through a 3',5'
      O-di-tert-butylsilanediyl protection, has been applied for the synthesis of [1'
      13C]ribonucleoside phosphoramidite units. This method allowed us to obtain only
      the desired 2'-O-silyl-3'-O-phosphoramidites avoiding the undesired 3'-O-silyl-2'
      O-phosphoramidite nucleosides isolated by standard procedures. This is a suitable
      procedure to RNA precursors with respect to the isotope-containing precursors.

PMID- 11284509
TI  - Salt-assisted acid hydrolysis of starch to D-glucose under microwave irradiation.
AB  - The effect of inorganic salts on the hydrolysis of starch in a microwave field
      was investigated and it was found that some inorganic salts can effectively
      accelerate the acid hydrolysis of starch. The yield of D-glucose reached 111 wt%
      (equal to the theoretical yield).

PMID- 11284510
TI  - A short and practical route to 3-O-benzoyl azidosphingosine.
AB  - A short and practical route to 3-O-benzoyl azidosphingosine from D-xylose is
      described. The synthesis avoids the use of expensive and hazardous chemicals
      (i.e. mercury salts), and it is reproducible up to at least a 20 g scale.
      Furthermore, the synthesis proceeds to 3-O-benzoyl azidosphingosine with a
      minimum of protection group manipulation, by exploiting a regioselective
      protection of the primary HO-1 with thexyldimethylsilyl chloride.

PMID- 11284511
TI  - Structural characterization of the glycan part of glycoconjugate LbGp2 from
      Lycium barbarum L.
AB  - A glycoconjugate with pronounced immunoactivity, designated as LbGp2, was
      isolated from the fruit of Lycium barbarum L. and purified to homogeneity by gel
      filtration. Its carbohydrate content is up to 90.71% composed of Ara, Gal and
      amino acids. The molecular weight is 68.2 kDa as determined by size exclusive
      chromatography (SEC). The complete structure of the repeat unit of the glycan of
      LbGp2 was elucidated based on glycosidic linkage analysis, total acid hydrolysis,
      partial acid hydrolysis, 1H and 13C NMR spectroscopy. According to the
      experiments, the glycan possesses a backbone consisting of (1-->6)-beta
      galactosyl residues, about fifty percent of which are substituted at C-3 by
      galactosyl or arabinosyl groups and the major nonreducing end being made of Ara
      (1 -->.

PMID- 11284512
TI  - Neurologic abnormalities in human immunodeficiency virus infection.
AB  - Neurologic abnormalities involving the central and peripheral nervous system are
      common in patients infected with the human immunodeficiency virus (HIV). Evidence
      of central nervous system infection (cerebrospinal fluid abnormalities) occurs
      early; however, evidence of central and peripheral nervous system dysfunction
      usually occurs at later stages. Neurologic manifestations may be due to chronic
      immunosuppression, direct neurotropic effect of HIV, or medication effects. It is
      important to recognize that brain and spine imaging studies are highly sensitive
      in detecting abnormal pathologic processes, but these studies have low
      specificity for establishing a specific pathologic diagnosis.

PMID- 11284513
TI  - Noncompliance of health care workers with universal precautions during trauma
      resuscitations.
AB  - BACKGROUND: Universal precautions during resuscitations are mandated by hospital
      regulations. We documented adherence to universal precautions during trauma
      resuscitations at our level I trauma center. METHODS: During trauma
      resuscitations, a medical student using an elevated viewing platform observed
      health care workers (HCWs) for the use of barrier precautions (BPs): gloves,
      masks, gowns, and eyewear. Only HCWs having direct patient contact were included.
      The purpose of the observation was not disclosed to those being observed.
      RESULTS: In 12 resuscitations involving 104 HCWs, none had 100% compliance with
      BPs. Compliance rates for individual BPs were gloves, 98%; eyewear (any type),
      52%; gowns, 38%; masks, 10%; and eyewear (with side protectors), 9%.
      Resuscitations in which bleeding was observed involved 59 HCWs with 38%
      compliance; only 2 used full BPs. No difference in compliance rates occurred
      during the study period. CONCLUSIONS: Experienced trauma care HCWs are cavalier
      regarding blood-borne disease exposure risks. Measures to encourage (or force)
      compliance are needed.

PMID- 11284514
TI  - Digital signature technology for health care applications.
AB  - BACKGROUND: The personal computer and the Internet have provided many useful
      services to both health care professionals and the general public. However,
      security remains a key factor that could limit their further growth potential.
      METHODS: We reviewed and assessed the potential use of the cryptographic
      technique to resolve security issues. We also analyzed services available in the
      current market environment and determined their viability in supporting health
      care applications. RESULTS: While the cryptographic application has a great
      potential in protecting security of health care information transmitted over the
      Internet, a nationwide security infrastructure is needed to support deployment of
      the technology. Although desirable, it could be cost prohibitive to build a
      national system to be dedicated for the health care purpose. CONCLUSIONS: A
      hybrid approach that involves the government's development of a dedicated
      security infrastructure for health care providers and the use of commercial off
      the-shelf products and services by the general public offers the most cost
      effective and viable approach.

PMID- 11284515
TI  - Breast conservation in the treatment of breast cancer: community-based
      experience.
AB  - BACKGROUND: Results of large, randomized studies in the 1980s established wide
      excision and radiation as an accepted breast cancer treatment approach. We
      evaluated our initial results with this treatment in the community setting.
      METHODS: We evaluated the frequency and outcome of breast conservation treatment
      in 303 women with invasive ductal carcinoma from 1985 to 1995. RESULTS: The
      frequency of breast conservation treatment increased from 9% during 1985 to 1989
      to 24% during 1990 to 1995. With a median follow-up of 4.7 years, there were 19
      (6%) ipsilateral recurrences. Metastatic disease occurred in 23 patients (8%).
      Overall 5-year survival was 95%, and 5-year recurrence-free survival was 90%.
      Twelve patients died of breast cancer. CONCLUSIONS: Increased use of breast
      conservation in our community practice parallels the national trend, with similar
      treatment results. Our findings suggest the successful integration of research
      proven innovations into community practice.

PMID- 11284516
TI  - Effect of literacy on breast-feeding outcomes.
AB  - BACKGROUND: We studied the effect of functional health literacy on the initiation
      and continuance of breast-feeding in women at a public health clinic. METHODS:
      Subjects were 61 first-time mothers aged 18 years or older who spoke English as
      their first language. They were divided into two groups, one who exclusively
      breast-fed for at least the first 2 months and one who never initiated breast
      feeding or did not exclusively breast-feed for at least 2 months. The Rapid
      Estimate of Adult Literacy in Medicine (REALM) was administered, providing
      reading grade-level estimates for each subject. RESULTS: An association between
      functional health literacy and breast-feeding was seen, with only 23% of the
      women in the lower literacy group exclusively breast-feeding during the first 2
      months compared with 54% of women in the higher literacy group. CONCLUSION: Many
      patients need simpler health education materials encouraging breastfeeding. These
      materials are needed both before and during pregnancy.

PMID- 11284517
TI  - Smoking cessation counseling practices: a survey of Alabama obstetrician
      gynecologists.
AB  - BACKGROUND: Minimal interventions delivered by obstetrician-gynecologists (OB
      GYNs) to their pregnant patients who smoke could result in a substantial decrease
      in smoking during pregnancy. We examined performance and motivation levels of
      Alabama OB-GYNs for engaging in clinical practices based on National Cancer
      Institute (NCI) guidelines. METHODS: Questionnaires assessing attitudes,
      intentions, and behaviors specified by the NCI's "4-A" model (ask, advise,
      assist, and arrange follow-up) were mailed to all OB-GYNs licensed in Alabama.
      RESULTS: A total of 130 physicians completed the questionnaire. Nearly all
      reported that they ask (93%) and advise (90%) their patients who smoke to quit;
      however, significantly fewer reported that they assist (28%) or arrange follow-up
      (24%) with their pregnant patients. CONCLUSIONS: Interventions are needed to
      motivate, support, and guide OB-GYN physicians to assist and follow-up with their
      pregnant patients who smoke.

PMID- 11284519
TI  - Influenza and pneumococcal immunization rates among a high-risk population.
AB  - BACKGROUND: Influenza and pneumococcal infections are the most vaccine
      preventable infectious diseases among the elderly population. Elderly patients
      (65 years and older) with chronic diseases derive substantial benefit from having
      current immunization status due to their high risk for respiratory diseases.
      However, immunization levels for influenza and pneumococcus remain suboptimal.
      This study sought to determine the immunization rates in a high-risk geriatric
      population. METHODS: Charts of consecutive patients seen in a geriatric clinic
      from November 1999 to February 2000 were obtained. Medical records were reviewed
      to assess their influenza and pneumococcal immunization status. RESULTS: Of 200
      patients who qualified for the study, all had at least two indications for
      vaccination, yet only 34% were current with influenza immunization, and 26% were
      current with pneumococcus immunization. CONCLUSIONS: In a high-risk elderly
      population, influenza and pneumococcal immunization rates were low. Patients who
      received pneumococcus vaccination were more likely to receive influenza
      immunization as well.

PMID- 11284518
TI  - Effects of antimanic mood-stabilizing drugs on fetuses, neonates, and nursing
      infants.
AB  - Pregnancy presents a special problem to the clinician treating bipolar disorders
      in women. Since the first episode of mania typically occurs before the age of 30,
      many women in their prime childbearing years may be exposed to potentially
      teratogenic mood-stabilizing agents. This exposure may also continue for the
      nursing infant during lactation. Pregnancy itself can exacerbate bipolar symptoms
      and also alter the pharmacokinetics of mood-stabilizing drugs. Risks to mother
      and fetus can be reduced with a number of simple strategies, including
      monotherapy with the lowest effective dose of a drug for the shortest period
      necessary, periconceptional use of multivitamins with folate, prescription of
      drugs with established safety records, and avoidance of exposure to antimanic
      agents during the first trimester of pregnancy. In this article, we review
      existing evidence on the risks to fetuses and nursing infants of mothers taking
      specific mood-stabilizing agents, and we present appropriate management
      guidelines designed to minimize these risks.

PMID- 11284520
TI  - Artificial skin in the treatment of a large congenital nevus.
AB  - An 8 year-old girl had a large congenital nevus involving the posterior thigh,
      leg, and foot. The nevus on non-weight-bearing areas was resected, and the areas
      were resurfaced with artificial skin and ultra-thin split-thickness grafts. A
      good result was ultimately achieved. Our management of this case and the relative
      merits of this new technology are detailed.

PMID- 11284521
TI  - Humoral hypercalcemia of malignancy in squamous cell carcinoma of the skin:
      parathyroid hormone--related protein as a cause.
AB  - The second most common cause of hypercalcemia is humoral hypercalcemia of
      malignancy (HHM), a condition associated with increased mortality. Although
      hypercalcemia is usually seen in squamous cell cancers, only 13 cases have been
      described in association with squamous cell skin cancer, and only 5 of these had
      characteristics of HHM. We report a case of hypercalcemia due to squamous cell
      skin cancer confined to the chest wall in a 67-year-old semi-comatose patient.
      Aggressive treatment with intravenous fluid hydration, furosemide, and etidronate
      corrected the hypercalcemia. A thorough workup ruled out bone metastasis and
      confirmed increased parathyroid-related protein, the hallmark of HHM. After
      regaining consciousness, the patient refused further therapy and subsequently
      died.

PMID- 11284522
TI  - Chest pain: overlooked manifestation of unsuspected esophageal foreign body.
AB  - Two cases of unsuspected esophageal foreign body ingestion with chest pain as the
      main symptom are reported. Both patients had extensive cardiac evaluation to rule
      out myocardial ischemia. They were discharged home with continuing chest pain and
      odynophagia. Both patients were denture wearers, and further questioning revealed
      the coincidence of chest pain with taking meals. Further evaluation revealed an
      impacted esophageal foreign body in one patient and an esophageal perforation
      with a mediastinal abscess in the other. These cases illustrate the importance of
      considering esophageal foreign bodies as factors in chest pain.

PMID- 11284523
TI  - Hepatic angiosarcoma: an unusual cause of congestive heart failure.
AB  - Hepatic angiosarcoma is a rare form of liver cancer. The history, physical
      examination, and liver biopsy are nonspecific. As a result, diagnosis of
      angiosarcoma can be challenging. We report the case of an elderly woman with
      congestive heart failure caused by a hepatic angiosarcoma. The massive tumor
      burden created extensive arteriovenous shunting and a high-cardiac-output state.

PMID- 11284524
TI  - Unusual presentation of primary hyperparathyroidism with osteoporosis,
      hypercalcemia, and normal parathyroid hormone level.
AB  - We report the case of a woman with osteoporosis, chronic hypercalcemia, and
      normal levels of parathyroid hormone (PTH). Surgical exploration revealed
      hyperplasia of the parathyroid glands. Hypercalcemia was corrected immediately by
      surgery, and this was followed by a dramatic improvement in bone mineral density.
      This case represents a rarely reported presentation of primary
      hyperparathyroidism with an atypical laboratory finding.

PMID- 11284525
TI  - Intravenous immunoglobulin therapy for Stevens-Johnson syndrome.
AB  - Stevens-Johnson syndrome (SJS) is an acute mucocutaneous disorder that can be
      associated with considerable morbidity. Several previous reports, all involving
      either adults with acquired immunodeficiency syndrome or children, suggest that
      intravenous immunoglobulin may be an effective treatment for SJS. We report a
      case of SJS in an immunocompetent adult whose condition improved dramatically
      after therapy with intravenous immunoglobulin.

PMID- 11284526
TI  - Congenital colonic stenosis.
AB  - We report the case of an infant with congenital colonic stenosis in the ascending
      colon and review the literature regarding this uncommon condition.

PMID- 11284527
TI  - Pancreatic pseudocyst with biliary fistula: treatment with endoscopic internal
      drainage.
AB  - Surgical drainage is the standard treatment for pancreatic pseudocysts and their
      complications. However, acute symptomatic pancreatic pseudocysts are amenable to
      endoscopic internal drainage in select cases. We report a case of pancreatic
      pseudocyst with biliary fistula resulting from a recurrent pseudocyst treated
      with endoscopic stent drainage.

PMID- 11284528
TI  - Newly diagnosed human immunodeficiency virus after sepsis-like reaction of
      trimethoprim-sulfamethoxazole.
AB  - A rare sepsis-like hypersensitivity reaction has been observed in persons with
      human immunodeficiency virus (HIV) after exposure to trimethoprim
      sulfamethoxazole. This reaction most commonly occurs on rechallenge with the drug
      and is manifested by a syndrome resembling bacterial sepsis. The mechanism of
      this unusual reaction remains unclear. We describe the first case in which this
      severe hypersensitivity reaction was the initial manifestation of HIV.

PMID- 11284529
TI  - Vancomycin-resistant Enterococcus faecium osteomyelitis: successful treatment
      with quinupristin-dalfopristin.
AB  - Vancomycin-resistant enterococci (VRE) have recently emerged as an increasing
      concern in the management of severe infections. Treatment of these life
      threatening infections has been limited to quinupristin-dalfopristin and, more
      recently, linezolid therapy. We report the first case, to our knowledge, of
      vancomycin-resistant Enterococcus faecium vertebral osteomyelitis treated
      successfully with quinupristin-dalfopristin. We review the recent epidemiology of
      VRE and briefly outline the pharmacology and pharmacokinetics of quinupristin
      dalfopristin.

PMID- 11284530
TI  - Complicated persistent patent ductus arteriosus with acute pneumonia in an adult.
AB  - Patent ductus arteriosus (PDA) is a malady usually identified during childhood.
      Prompt surgical correction provides definitive therapy with long-term survival.
      When not corrected, PDA leads to significant morbidity and mortality, making it a
      rare condition in the adult population. We report the case of a 44-year-old man
      with a history of persistent PDA admitted for worsening dyspnea and fever.
      Radiographic studies are illustrative of this complex syndrome. We review the
      complications and treatment alternatives in these patients.

PMID- 11284531
TI  - A clinical application of autotransplantation using furcation-involved root.
AB  - BACKGROUND, AIMS: The present case report describes the clinical application of
      autotransplantation using furcation involved roots. METHOD: After initial
      therapy, root resection was performed upon the patient's molar teeth with
      furcation involvement in the mandible. 2 distal roots of the molar teeth were
      autotransplanted as abutments to replace missing premolar and molar teeth in the
      mandible. RESULTS: On re-examination, 1 year after the transplantation, these
      roots showed no signs of periodontal or technical complications. The results
      suggest the potential use of autotransplantation techniques using furcation
      involved roots in reconstructive therapy. This may be a new approach in
      periodontal therapy.

PMID- 11284532
TI  - Self-preventive oral behavior in an Italian university student population.
AB  - BACKGROUND/AIM: The aim of this study was to assess the oral hygiene attitude and
      the professional preventive examination compliance in Italian university
      students. METHOD: A sample of 202 students attending the University of Bologna
      was randomly selected and interviewed about their preventive oral health attitude
      and compliance. All students reported using toothpaste and most of them (92.1%)
      brushed their teeth at least 2x a day using artificial, medium stiffness
      bristles. The toothbrush was generally (81.6%) replaced within 3 months. Few
      subjects (14.9%) said they used dental floss daily or utilized other devices. A
      majority of subjects (59.9%) had a dental examination within the year previous to
      the interview. Cluster analysis was performed. RESULTS: 4 groups were identified
      with homogeneous oral hygiene behavior and compliance toward professional
      preventive examination. Only one cluster, representing 33.6% of the sample,
      showed consistent frequency and modalities of oral hygiene habits. The other
      clusters seemed to be defective with interproximal cleaning procedures and
      compliance toward professional preventive care. Since the sample was
      characterized by a young, urbanized, homogeneous group with a high educational
      level and frequently from an upper middle class social status, the analysis
      probably gives a supra-estimation of the positive behavior. CONCLUSION: It is
      rational to suppose that strategies to promote dental service utilization,
      patients' compliance and a professional style oriented toward prevention may be
      useful to improve the oral health condition in the young adult Italian
      population.

PMID- 11284533
TI  - Smoking and subgingival microflora in periodontal disease.
AB  - AIM: The present investigation was undertaken to analyze the influence of smoking
      on the periodontal disease associated subgingival microflora. The population
      included 33 smokers and 31 non-smokers in the age range 36-86 years. METHODS:
      Microbial samples were obtained from 4 sites per patient. The checker-board DNA
      DNA hybridization technology was used for detection of the bacterial species P.
      gingivalis, P. intermedia, P. nigrescens, B. forsythus, A. actinomycetemcomitans,
      F. nucleatum, T. denticola, P. micros, C. rectus, E. corrodens, S. noxia and S.
      intermedius. RESULTS: Using score 1 as cutoff, contrasting colonized versus non
      colonized patients, 8 out of 12 species were detected in > or = 90% of both
      smokers and non-smokers. Using score 4 as cutoff, contrasting heavily colonized
      patients versus non-colonized and less heavily colonized patients, the detection
      rates decreased in both smokers and non-smokers. No significant differences in
      detection rates were observed between smokers and non-smokers. Logistic
      regression analysis indicated that neither smoking, probing depth nor gingival
      bleeding influenced the occurrence of the species analyzed. The lack of a smoking
      exposure dose-response further supported the indication of a limited influence of
      smoking. CONCLUSION: Smoking exerts little, if any, influence on the subgingival
      occurrence of several of the bacteria most commonly associated with periodontal
      disease.

PMID- 11284534
TI  - The effect of working tip angulation on root substance removal using Er:YAG laser
      radiation: an in vitro study.
AB  - OBJECTIVES: The present investigation attempted to determine the amount of
      cementum and/or dentin removal with Er:YAG laser radiation, dependent on the
      angulation of a specially-developed application tip. MATERIAL AND METHODS:
      Subject of the study were 150 extracted incisors, canines, premolars, and molars.
      Source of laser radiation was an Er:YAG laser device emitting pulsed infrared
      radiation at a wavelength of 2.94 microm with a pulse duration of 250 micros and
      a pulse repetition rate of 10 pps. The samples of the 3 study groups were
      irradiated with 380 laser pulses at radiation energies of 60 mJ (group A), 100 mJ
      (group B), or 180 mJ (group C). In each group, 10 samples were treated at working
      tip angulations of 15 degrees , 30 degrees , 45 degrees , 60 degrees , and 90
      degrees. The substance removal was determined 3-dimensionally using a newly
      developed laser scanning system (100,000 surface points per sample, accuracy 5
      microm) and a special image-analysing software (Match 3D). Statistical analysis
      was completed with ANOVA followed by multiple comparisons using the Scheffe-test
      and with linear regression analysis according to Pearson-Bravais (p < 0.05).
      RESULTS: Strong dependence of substance removal, both determined as maximum depth
      of the defects (0.5% quantil) as well as defect volume, on the angulation of the
      working tip was shown. At 60 mJ, the depth of the defects was 41.39 (+/- 32.55)
      microm at an angulation of 15 degrees and that at 90 degrees was 181.39 (+/-
      74.42) microm (R2= 0.921). For the radiation energy at 100 mJ, the depth of the
      defects ranged from 51.96 (+/- 26.86) microm at 15 degrees to 306.64 (+/- 62.44)
      microm at 90 degrees (R2 = 0.983). Choosing radiation energies at 180 mJ, the
      depth of the defects ranged from 64.73 (+/- 27.73) microm at 15 degrees to 639.89
      (+/- 47.28) microm at 90 degrees , on average (R2 = 0.853). CONCLUSIONS: The
      results of the present study provide clear evidence that besides the physical
      radiation parameters, also the parameters of clinical handling, in particular the
      angulation of the application tip, has a strong influence on the amount of root
      substance removal using Er:YAG laser radiation.

PMID- 11284535
TI  - Retrospective comparison of clinical variables between compliant and non
      compliant patients.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate if patients with
      moderate to advanced periodontitis had comparable periodontal conditions at
      baseline and during supportive periodontal therapy (SPT) whether they were
      compliant or not. METHOD: Patient-related variables were compared: age, tooth
      mobility, furcation involvement, number of teeth, pocket probing depth, plaque
      index. Compliant patients (n = 142) received complete periodontal treatment and
      were followed over at least 10 years (group A). Non-compliant patients either
      discontinued supportive periodontal therapy (n = 42, group B) or dropped out
      before or during periodontal surgery (n = 44, group C). RESULTS: At baseline,
      there were no significant differences between the 3 groups except for mobility.
      During SPT, mean pocket probing depth and plaque index differed significantly.
      CONCLUSION: These results indicate that non-compliant patients compared to
      compliant patients had similar periodontal conditions at baseline, but responded
      less favourably to periodontal surgery and maintenance.

PMID- 11284536
TI  - Soluble antagonists to interleukin-1 (IL-1) and tumor necrosis factor (TNF)
      inhibits loss of tissue attachment in experimental periodontitis.
AB  - BACKGROUND, AIMS: Periodontal disease is a significant cause of tooth loss among
      adults and is characterized by the alteration and permanent destruction of the
      deeper periodontal tissues. Although the presence of pathologic microbes is
      required to trigger this process, the amplification and progression of the
      diseased state is believed to rely heavily on the production of host mediators in
      response to bacteria or their metabolic products. The inflammatory response is
      effective in preventing large-scale colonization of the gingival tissues by
      bacteria that lie in close proximity to the tooth surface or within the gingival
      sulcus. It has been postulated that the host-response in some individuals may
      lead to an over-reaction to invading oral pathogens resulting in the destruction
      of periodontal tissues. METHODS: Several host-derived mediators are believed to
      contribute to this response. Two agents considered to be essential in periodontal
      destruction are interleukin-1 (IL-1) and tumor necrosis factor (TNF). We
      investigated the role of IL-1 and TNF in the loss of connective tissue attachment
      in a Macaca fascicularis primate model of experimental periodontitis. Silk
      ligatures impregnated with the periodontal pathogen, Porphyromonas gingivalis
      were wrapped around the posterior teeth and the activity of IL-1 and TNF were
      inhibited by soluble receptors to these proinflammatory cytokines via local
      injection into interdental papillae. RESULTS: Histomorphometric analysis
      indicates that IL-1 and TNF antagonists significantly reduced the loss of
      connective tissue attachment by approximately 51% and the loss of alveolar bone
      height by almost 91%, both of which were statistically significant. CONCLUSION:
      This investigation demonstrates that the loss of connective tissue attachment and
      progression of periodontal disease can be retarded by antagonists to specific
      host mediators such as IL-1 and TNF and may provide a potential treatment
      modality to combat the disease process.

PMID- 11284537
TI  - Longitudinal periodontal tissue alterations during supportive therapy. Findings
      from subjects with normal and high susceptibility to periodontal disease.
AB  - AIM: The aim of the study was to evaluate disease progression during supportive
      periodontal therapy in (i) a group of 225 subjects with "normal" (NG) and (ii) a
      group with high susceptibility (HSG; n= 109) to periodontal disease (based on
      their baseline disease status). MATERIAL AND METHODS: The following variables
      were recorded at the baseline examination (1 year after they received non
      surgical periodontal therapy) and at the re-examination after 12 years of
      maintenance: number of teeth, plaque, probing pocket depth, probing attachment
      level, bone level in full mouth radiographs. All assessments were performed in a
      standardized manner and by well-trained and calibrated examiners. Supportive
      periodontal therapy was delivered 3-4 x per year and included repeated oral
      hygiene instruction and debridement. In addition, sites that bled on probing and
      had a PPD value of > or = 5 mm received subgingival instrumentation. RESULTS: A
      comparison between the findings at baseline and after 12 years revealed that in
      the NG, most subjects maintained their periodontal condition unchanged during the
      maintenance period; only a few subjects experienced tooth loss and the figures
      describing the mean amount of bone and attachment loss were small (0.5 mm and 0.3
      mm respectively). The HSG patients experienced some tooth loss and also lost
      significant amounts of bone and attachment during the 12 years of SPT. Thus, in
      this group of subjects, the mean overall PAL loss amounted to 0.8 mm, i.e., 0.06
      mm/tooth surface/year. In the NG, the overall attachment loss was significantly
      smaller: 0.5 mm, i.e. 0.04 mm/tooth surface/year. CONCLUSION: In subjects with a
      high susceptibility for periodontal disease who had been treated for this
      condition by non-surgical means, an SPT program including regularly repeated oral
      hygiene instruction and subgingival debridement, made it possible to maintain
      bone and attachment levels at a reasonably stable level over a 12-year period. A
      similar SPT provided to a group of subjects with normal susceptibility to
      periodontal disease, on the other hand, prevented almost entirely major tooth,
      bone and attachment loss.

PMID- 11284538
TI  - Intra-examiner reproducibility of 4 dental plaque indices.
AB  - BACKGROUND, AIMS: The aim of the present study was to assess the intra-examiner
      reproducibility for 2 established ordinal plaque indices and 2 newly proposed
      interval plaque indices. METHOD: 15 subjects received a professional tooth
      cleaning and interrupted all oral hygiene measures for 48 to 62 hours. Plaque
      accumulation was scored 2x for all canines, premolars and 1st and 2nd molars in
      the 1st and 3rd quadrants with the visual plaque index (VPI), the modified navy
      plaque index (mNPI), the axial plaque extension index (APEI) and the proximal
      plaque extension index (PPEI). 147 teeth (57 molars, 60 premolars, 30 canines)
      were scored. RESULTS: No statistically significant differences were found for
      duplicate measurements with all indices, except for buccal and lingual VPI (p <
      0.05. Wilcoxon test) and for buccal APEI (p < 0.01, t-test). High correlations
      existed between all duplicate measurements with r-values ranging from 0.76 to
      0.94. For the VPI, 78% of buccal (kappa = 0.70) and 89% of lingual (kappa = 0.75)
      scores were identical, whereas this was the case for 88% of buccal (kappa = 0.81)
      and for 73% of lingual (kappa = 0.62) mNPI scores. For APEI and PPEI scores a
      linear regression was found with slopes ranging between 0.76 and 1.00. For these
      indices, the mean measurement error ranged between 0.4 and 9.1%. Results were
      comparable for VPI, mNPI and PPEI, whereas APEI appeared slightly less
      reproducible. CONCLUSION: In conclusion, a high intra-examiner reproducibility
      was found for all plaque indices tested, both the ordinal and the interval
      indices.

PMID- 11284539
TI  - The effect of chewing sugar-free gum on plaque regrowth at smooth and occlusal
      surfaces.
AB  - BACKGROUND AND AIM: Chewing gum has the potential to provide oral health benefits
      including plaque control. The aim of this study was to determine the effects of
      chewing sugar free gum on plaque regrowth at buccal, lingual and occlusal
      surfaces of teeth. METHOD AND MATERIALS: 11 healthy and dentally-fit dental
      hygiene students participated in this randomised, single-blind crossover 4-day
      plaque regrowth study. From a zero plaque score on day 1, subjects suspended oral
      hygiene measures and either chewed gum or did not chew gum over 4 days. Gum
      chewing was one piece chewed for 30 min 4 x per day. On day 4, subjects were
      scored for plaque after disclosing from buccal, lingual and unrestored occlusal
      surfaces. RESULTS: There was no significant difference in smooth surface plaque
      scores between the treatments but significantly less plaque accumulated (44%) at
      occlusal surfaces during gum chewing compared to no gum chewing. CONCLUSION:
      Chewing gum can reduce plaque accumulation at sites of predilection for caries
      but has little or no effect at sites of predilection for gingivitis.

PMID- 11284540
TI  - Osseintegration following treatment of peri-implantitis and replacement of
      implant components. An experimental study in the dog.
AB  - AIM: The aim of the present experiment was to study if the quality of the
      titanium surface is a decisive factor for osseointegration and re
      osseointegration. MATERIAL AND METHODS: 2 Labrador dogs were used. The mandibular
      1st molars and all premolars were removed bilaterally. 3 months later, 1 standard
      fixture and 3, 2-part "test fixtures" were installed in each side of the
      mandible. The text fixtures consisted of 1 6-mm long apical and 1 4-mm long
      coronal part connected with an internal screw. After 4 months, abutment
      connection was performed. 5 months later, a period of experimental peri
      implantitis was initiated during which about 50% of the supporting bone tissue
      was lost. The dogs were later subjected to a treatment that included (i) systemic
      administration of antibiotics and (ii) surgical debridement of all implant sites.
      The abutments and the coronal parts of the text fixtures were removed. All parts
      of the exposed portion of the standard fixtures, the connecting screw and the
      apical part of the test fixtures were meticulously cleaned by mechanical means. A
      pristine, coronal fixture part was via the connecting screw attached to the
      apical fixture part of each text fixture. All fixtures were submerged. 2 weeks
      later, a fluorochrome was injected intravenously. After 4 months, biopsies of the
      implant sites were dissected and prepared for ground sectioning and analysis.
      RESULTS: It was demonstrated that re-osseointegration failed to occur to implant
      surfaces (standard) exposed to bacterial contamination, but did consistently
      occur at sites where a pristine implant component was placed in the bone defect
      following surgical debridement. CONCLUSION: The above findings seem to imply that
      the quality of the titanium surface is of decisive importance for both
      osseointegration and re-osseointegration.

PMID- 11284541
TI  - Periodontal status and serum antibody titers for Porphyromonas gingivalis
      fimbriae in a rural population in Japan.
AB  - BACKGROUND, AIMS: The present study was undertaken to assess the periodontal
      status of a rural Japanese population and to study the correlation between the
      periodontal status and the serum antibody titers for Porphyromonas gingivalis
      (Pg) fimbriae. METHOD: A total of 236 individuals were examined for their
      periodontal conditions by the use of the community periodontal index for
      treatment needs (CPITN), and serum antibody titers for Pg fimbriae in their
      peripheral blood samples were evaluated using the enzyme-linked immunosorbent
      assay. RESULTS: There was a substantially larger proportion of edentulous
      subjects in the age group older than 60 years. The remaining teeth were 24.1,
      23.2, 11.1 and 10.1 per person in the 40-49, 50-59, 60-69 and > or = 70 age
      groups, respectively. The % of sextants with a CPITN code of missing sextant (MS)
      increased towards elderly and reached >60% in the age group of > or = 70 years,
      as the % of the CPITN 2, 1 or 0 sextant decreased. The % of CPITN 4 and 3
      sextants did not differ between different age groups and were about 6-8% and 15
      20%, respectively. The % of CPITN 1 or 0 sextants was higher in female subjects
      than in male subjects in the 60-69 and > or = 70 age groups, while the % of CPITN
      4 or 3 sextants was higher in male subjects than in female subjects in all age
      groups. There was no significant difference between various age groups in the
      mean serum antibody titers for Pg fimbriae. The mean anti-Pg fimbriae antibody
      titers was significantly higher for the subjects with a maximum CPITN code 4
      (max.-CPITN 4 subject) than for the subjects with lower maximum CPITN codes. The
      antibody titers varied extensively among the max.-CPITN 4 or 3 subjects, but not
      among the max.-CPITN 2/1/0 or MS subjects. CONCLUSIONS: The present study
      demonstrated that tooth loss is a remarkable event in elderly subjects and that
      oral prophylaxis and mechanical debridement should be mandatory in the population
      examined. It was also demonstrated that the serum antibody titers against Pg
      fimbriae could be useful for screening individuals with moderate to severe
      periodontitis.

PMID- 11284543
TI  - Adverse effects of arecoline and nicotine on human periodontal ligament
      fibroblasts in vitro.
AB  - BACKGROUND, AIMS: The habit of betel nut chewing impinges on the daily lives of
      approximately 200 million people. Betel quid chewers have a higher prevalence of
      periodontal diseases than non-chewers. This study examined the pathobiological
      effects of arecoline, a major component of the betel nut alkaloids, on human
      periodontal ligament fibroblasts (PDLF) in vitro. METHOD: Cell viability,
      proliferation, protein synthesis, and cellular thiol levels were used to
      investigate the effects of human PDLF exposed to arecoline levels of 0 to 200
      microg/ml. In addition, nicotine was added to test how it modulated the effects
      of arecoline. RESULTS: Arecoline significantly inhibited cell proliferation in a
      dose-dependent manner. At concentrations of 10 and 30 microg/ml, arecoline
      suppressed the growth of PDLF by 20% and 50% (p < 0.05), respectively. Arecoline
      also decreased protein synthesis in a dose-dependent manner during a 24-h culture
      period. A 100 microg/ ml concentration level of arecoline significantly inhibited
      protein synthesis to only 50% of that in the untreated control (p < 0.05).
      Moreover, arecoline significantly depleted intracellular thiols in a dose
      dependent manner. At concentrations of 25 microg/ml and 100 microg/ml, arecoline
      depleted about 18% and 56% of thiols (p < 0.05), respectively. This suggests that
      arecoline itself might augment the destruction of periodontium associated with
      betel nut use. Furthermore, the addition of nicotine acted with a synergistic
      effect on the arecoline-induced cytotoxicity. At a concentration of 60 microg/ml,
      arecoline suppressed the growth of PDLF by about 33% and 5 mM nicotine enhanced
      the arecoline-induced cytotoxic response to cause about 66% cell death.
      CONCLUSION: During thiol depletion, arecoline may render human PDLF more
      vulnerable to reactive agents within cigarettes. Taken together, people who
      combine habits of betel nut chewing with cigarette smoking could be more
      susceptible to periodontium damage than betel nut chewing alone.

PMID- 11284542
TI  - Effects of SCN-/H2O2 combinations in dentifrices on plaque and gingivitis.
AB  - OBJECTIVES: A 10-week, double-blind, placebo-controlled clinical study on 140
      male subjects was conducted to determine the effect on plaque and gingivitis of 5
      dentifrices containing various thiocyanate (SCN-)/hydrogen peroxide (H2O2)
      combinations. MATERIALS AND METHODS: The dentifrices consisted of a gel base
      without any detergents or abrasives (placebo, group A) to which SCN- and/or H2O2
      were added as follows: 0.1% SCN- (group B), 0.5% SCN- (group C), 0.1% SCN-/0.1%
      H2O2 (group D), 0.5% SCN-/0.1% H2O2 (group E) and 0.1% H2O2 (group F). A baseline
      examination was performed in which the Silness and Loe Plaque Index (PI), the
      Muhlemann and Son Sulcus Bleeding Index (SBI), and the amount of gingival
      crevicular fluid (GCF) were recorded using the Periotron 6,000 on teeth 16, 12,
      24, 36, 32, and 44. The subjects were randomly assigned to either the placebo
      group (n = 40) or one of the test groups (n = 20) and used their respective
      dentifrices over a period of 8 weeks. Finally, each group used the placebo for
      another 2 weeks (wash-out). Re-examinations were performed after 1, 4, and 8
      weeks and the 2-week wash-out period employing the clinical parameters used at
      baseline. Intragroup changes were analyzed with the Wilcoxon signed-ranks test,
      using the baseline and wash-out points as references. The Mann-Whitney U test was
      used for comparisons between the treatment groups and the placebo group. RESULTS:
      At the 8-week examination, the plaque index in group E (p = 0.017) and group F (p
      = 0.032) was lower than in the placebo group. The Sulcus Bleeding Index in group
      F after 1 week was increased (p = 0.023) and the SBI in group E after 8 weeks was
      reduced (p = 0.047) as compared to the placebo group. CONCLUSION: The results
      demonstrated that a dentifrice containing 0.5% SCN- and 0.1% H2O2 but no
      detergents or abrasives inhibited plaque and decreased gingivitis.

PMID- 11284545
TI  - Decrease and recovery of N-acetylaspartate/creatine in rat brain remote from
      focal injury.
AB  - Magnetic resonance spectroscopy (MRS) studies on traumatic brain injury (TBI)
      have shown that the neuronal metabolite N-acetylaspartate (NAA) may be reduced in
      regions of brain remote from sites of focal injury. Such reductions have
      generally been attributed to diffuse axonal injury (DAI) or neuron death. The aim
      of the present study was to investigate the contribution of metabolic depression,
      in the absence of DAI or cell death, to remote NAA reduction after TBI. The right
      sensorimotor cortices of adult rats were injured by weight drop. Two and six days
      later, tissue slices from the ipsilateral occipital cortex, or from the same
      region in uninjured rats, were superfused and examined by 1H-MRS. The occipital
      cortex has been shown to have negligible DAI or cell death but marked transient
      metabolic depression in this model of TBI. Two days after injury, the ratio of
      the NAA peak height to the total creatine peak height (NAA/TCr) was 14% lower
      than in control samples. Six days after injury, NAA/TCr recovered to within 7% of
      the control value. The time course of NAA/TCr decrease and recovery was similar
      to the time courses of widespread depression and recovery of 2-deoxyglucose
      uptake and mitochondrial alpha-glycerophosphate dehydrogenase activity measured
      previously in this model of TBI. Together, these results suggest that at least
      one component of remote NAA depression after TBI may be associated with a
      widespread and reversible metabolic depression that is unrelated to either DAI or
      cell death.

PMID- 11284544
TI  - Altered cellular metabolism following traumatic brain injury: a magnetic
      resonance spectroscopy study.
AB  - Experimental studies have reported early reductions in pH, phosphocreatine, and
      free intracellular magnesium following traumatic brain injury using phosphorus
      magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some
      evidence for an increase in the pH in the subacute stage following traumatic
      brain injury. We therefore performed phosphorus magnetic resonance spectroscopy
      on seven patients in the subacute stage (mean 9 days postinjury) following
      traumatic brain injury to assess cellular metabolism. In areas of normal
      appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04
      [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to
      inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/-
      1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine
      triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10,
      controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly
      increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients
      compared to controls. Furthermore, the calculated free intracellular magnesium
      was significantly increased in the patients compared to the controls (patients
      0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired
      from similar regions showed a significant reduction in N-acetylaspartate
      (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a
      significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67
      +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control
      spectrum. The alterations in metabolism observed in these patients could not be
      explained by ongoing ischemia but might be secondary to a loss of normal cellular
      homeostasis or a relative alteration in the cellular population, in particular an
      increase in the glial cell density, in these regions.

PMID- 11284546
TI  - A new model for diffuse brain injury by rotational acceleration: I model, gross
      appearance, and astrocytosis.
AB  - Rapid head rotation is a major cause of brain damage in automobile crashes and
      falls. This report details a new model for rotational acceleration about the
      center of mass of the rabbit head. This allows the study of brain injury without
      translational acceleration of the head. Impact from a pneumatic cylinder was
      transferred to the skull surface to cause a half-sine peak acceleration of 2.1 x
      10(5) rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and
      small focal bleedings were observed in the brain tissue. A pronounced reactive
      astrogliosis was found 8-14 days after trauma, both as networks around the focal
      hemorrhages and more diffusely in several brain regions. Astrocytosis was
      prominent in the gray matter of the cerebral cortex, layers II-V, and in the
      granule cell layer and around the axons of the pyramidal neurons in the
      hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial
      nerves, also showed intense astrocytosis. The new model allows study of brain
      injuries from head rotation in the absence of translational influences.

PMID- 11284547
TI  - A new model for diffuse brain injury by rotational acceleration: II. Effects on
      extracellular glutamate, intracranial pressure, and neuronal apoptosis.
AB  - The aim of this study is to monitor excitatory amino acids (EAAs) in the
      extracellular fluids of the brain and to characterize regional neuronal damage in
      a new experimental model for brain injury, in which rabbits were exposed to 180
      260 krad/s2 rotational head acceleration. This loading causes extensive
      subarachnoid hemorrhage, focal tissue bleeding, reactive astrocytosis, and axonal
      damage. Animals were monitored for intracranial pressure (ICP) and for amino
      acids in the extracellular fluids. Immunohistochemistry was used to study
      expression of the gene c-Jun and apoptosis with the terminal deoxynucleotidyl
      transferase nick-end labeling (TUNEL) technique. Extracellular glutamate,
      glycine, and taurine increased significantly in the hippocampus within a few
      hours and remained high after 24 h. Neuronal nuclei in the granule layers of the
      hippocampus and cerebellum were positive for c-Jun after 24 h. Little
      immunoreactivity was detected in the cerebral cortex. c-Jun-positive neuronal
      perikarya and processes were found in granule and pyramidal CA4 layers of the
      hippocampus and among the Purkinje cells of the cerebellum. Also some microglial
      cells stained positively for c-Jun. TUNEL reactivity was most intense at 10 days
      after trauma and was extensive in neurons of the cerebral cortex, hippocampus,
      and cerebellum. The initial response of the brain after rotational head injury
      involves brain edema after 24 h and an excitotoxic neuronal microenvironment in
      the first hour, which leads to extensive delayed neuronal cell death by apoptosis
      necrosis in the cerebral cortex, hippocampus and cerebellum.

PMID- 11284548
TI  - Infusion of prostacyclin following experimental brain injury in the rat reduces
      cortical lesion volume.
AB  - Endothelial-derived prostacyclin is an important regulator of microvascular
      function, and its main actions are inhibition of platelet/leukocyte aggregation
      and adhesion, and vasodilation. Disturbances in endothelial integrity following
      traumatic brain injury (TBI) may result in insufficient prostacyclin production
      and participate in the pathophysiological sequelae of brain injury. The objective
      of this study was to evaluate the potential therapeutic effects of a low-dose
      prostacyclin infusion on cortical lesion volume, CA3 neuron survival and
      functional outcome following TBI in the rat. Anesthetized animals (sodium
      pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain
      injury (2.5 atm) or sham injury. Following TBI, animals were randomized to
      receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or
      vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of
      neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly.
      By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in
      the prostacyclin-treated group as compared to the vehicle treated group (p <
      0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in
      neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss
      (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We
      conclude that prostacyclin in a low dose reduces loss of neocortical neurons
      following TBI and may be a potential clinical therapeutic agent to reduce
      neuronal cell death associated with brain trauma.

PMID- 11284549
TI  - Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord
      without immune suppression in adult rats.
AB  - Grafting of genetically modified cells that express therapeutic products is a
      promising strategy in spinal cord repair. We have previously grafted BDNF
      producing fibroblasts (FB/BDNF) into injured spinal cord of adult rats, but
      survival of these cells requires a strict protocol of immune suppression with
      cyclosporin A (CsA). To develop a transplantation strategy without the
      detrimental effects of CsA, we studied the properties of FB/BDNF that were
      encapsulated in alginate-poly-L-ornithine, which possesses a semipermeable
      membrane that allows production and diffusion of a therapeutic product while
      protecting the cells from the host immune system. Our results show that
      encapsulated FB/BDNF, placed in culture, can survive, secrete bioactive BDNF and
      continue to grow for at least one month. Furthermore, encapsulated cells that
      have been stored in liquid nitrogen retain the ability to grow and express the
      transgene. Encapsulated FB/BDNF survive for at least one month after grafting
      into an adult rat cervical spinal cord injury site in the absence of immune
      suppression. Transgene expression decreased within two weeks after grafting but
      resumed when the cells were harvested and re-cultured, suggesting that soluble
      factors originating from the host immune response may contribute to the
      downregulation. In the presence of capsules that contained FB/BDNF, but not cell
      free control capsules, there were many axons and dendrites at the grafting site.
      We conclude that alginate encapsulation of genetically modified cells may be an
      effective strategy for delivery of therapeutic products to the injured spinal
      cord and may provide a permissive environment for host axon growth in the absence
      of immune suppression.

PMID- 11284550
TI  - Enduring vulnerability to transient reinstatement of hemiplegia by prazosin after
      traumatic brain injury.
AB  - A single dose of an alpha1-noradrenergic antagonist transiently reinstates
      hemiplegia after recovery from brain injury, which suggests that noradrenaline
      (NA) is required to maintain recovery. No systematic studies have determined the
      postinjury duration of this vulnerability. This study used a within-subject, dose
      response design to determine whether prazosin (PRAZ), an alpha1-NA antagonist, or
      propranolol (PROP), a beta-NA antagonist, would continue to reinstate hemiplegia
      over time after recovery from weight-drop traumatic brain injury (TBI). PRAZ
      transiently reinstated hemiplegia as measured by beam walk (BW) score in a dose
      dependent manner, with the same degree of symptom reinstatement at 1, 3, 6, and
      12 months post-TBI. Between-animal variability in reinstatement of hemiplegia by
      PRAZ was predicted by severity of deficits in BW ability 24 h after TBI. In
      contrast, PRAZ did not reinstate tactile placing deficits at 1 month post-TBI
      suggesting a different mechanism of maintaining recovery for each task.
      Reinstatement of symptoms are not due to sedation. Only TBI rats receiving PRAZ,
      not high, sedating doses of PROP or saline (SAL), showed return of hemiplegia.
      These data indicate that vulnerability to transient reinstatement of hemiplegia
      on some tasks endures long after functional recovery from TBI.

PMID- 11284551
TI  - Short-Term and medium-term effects of spinal cord tract transections on soleus H
      reflex in freely moving rats.
AB  - Spinal cord function is normally influenced by descending activity from
      supraspinal structures. When injury removes or distorts this influence, function
      changes and spasticity and other disabling problems eventually appear.
      Understanding how descending activity affects spinal cord function could lead to
      new means for inducing, guiding, and assessing recovery after injury. In this
      study, we investigated the short-term and medium-term effects of spinal cord
      bilateral dorsal column (DC), unilateral (ipsilateral) lateral column (LC),
      bilateral dorsal column ascending tract (DA), or bilateral dorsal column
      corticospinal tract (CST) transection at vertebral level T8-T9 on the soleus H
      reflex in freely moving rats. Data were collected continuously for 10-20 days
      before and for 20-155 days after bilateral DC (13 rats), DA (10 rats), CST (eight
      rats), or ipsilateral LC (seven rats) transection. Histological examination
      showed that transections were 98(+/- 3 SD)% complete for DC rats, 80(+/- 20)%
      complete for LC rats, 91(+/- 13 SD)% complete for DA rats, and 95(+/-13)%
      complete for CST rats. LC, CST, and DA transections produced an immediate (i.e.,
      first-day) increase in H-reflex amplitude. LC transection also produced a small
      decrease in background activity in the first few posttransection days. Other than
      this small decrease, none of the transections produced evidence for the
      phenomenon of spinal shock. For all transections, all measures returned to or
      neared pretransection values within 2 weeks. DA and LC transections were
      associated with modest increase in H-reflex amplitude 1-3 months after
      transection. These medium-term effects must be taken into account when assessing
      transection effects on operant conditioning of the H-reflex. At the same time,
      the results are consistent with other evidence that, while H-reflex rate
      dependence and H-reflex operant conditioning are sensitive measures of spinal
      cord injury, the H-reflex itself is not.

PMID- 11284552
TI  - Sciatic nerve regeneration through alginate with tubulation or nontubulation
      repair in cat.
AB  - A novel material for nerve regeneration, alginate, was employed in both
      tubulation and nontubulation repair of a long peripheral nerve defect injury.
      Twelve cats underwent severing of the right sciatic nerve to generate a 50-mm
      gap, which was treated by tubulation repair (n = 6) or nontubulation repair (n =
      6). In the tubulation group, a nerve conduit consisting of polyglycolic acid mesh
      tube filled with alginate sponge was implanted into the gap and the tube was
      sutured to both nerve stumps. In the nontubulation group, the nerve defect was
      repaired by a simple interpolation of two pieces of alginate sponge without any
      suture. The animals in both groups exhibited similar recovery of locomotor
      function. Three months postoperatively, successful axonal elongation and
      reinnervation in both the afferent and efferent systems were detected by
      electrophysiological examinations. Intracellular electrical activity was also
      recorded, which is directly indicative of continuity of the regenerated nerve and
      restoration of the spinal reflex circuit. Eight months after operation, many
      regenerated myelinated axons with fascicular organization by perineurial cells
      were observed within the gap, peroneal and tibial branches were found in both
      groups, while no alginate residue was found within the regenerated nerves. In
      morphometric analysis of the axon density and diameter, there were no significant
      differences between the two groups. These results suggest that alginate is a
      potent material for promoting peripheral nerve regeneration. It can also be
      concluded that the nontubulation method is a possible repair approach for
      peripheral nerve defect injury.

PMID- 11284553
TI  - Self-Protective mechanism awakened by glutamate in retinal ganglion cells.
AB  - The progression of degeneration in chronic optic neuropathies or in animal models
      of optic nerve injury is thought to be caused, at least in part, by an increase
      in glutamate to abnormally high concentrations. We show here that glutamate, when
      injected in subtoxic amounts into the vitreal body of the rat eye, transduces a
      self-protecting signal that renders the retinal ganglion cells resistant to
      further toxicity, whether glutamate-derived or not. This neuroprotective effect
      is attained within 24 h and lasts at least 4 days. Western blot analysis of rat
      retinas revealed increased amounts of bcl-2 four days after injection of
      glutamate in either subtoxic or toxic (120 nmol) amounts, but not after saline
      injection. The effects of intravitreal glutamate or saline injection on the
      secretion of neurotrophins by retinal ganglion cells was evaluated in rat aqueous
      humor 6 h, 1 day, and 4 days after injection. Nerve growth factor, brain-derived
      neurotrophic factor, and neurotrophin-3 showed similar kinetic patterns in all of
      the eyes; that is, they increased to a peak 1 day after the injection and
      returned to normal by day 4. However, increased amounts the neurotrophin receptor
      TrkA within the retinal ganglion cell layer and nerve fiber layer were detected 1
      day after injection of glutamate in either toxic or subtoxic amounts, but not
      after saline injection. This finding points to the possible involvement of
      neurotrophin receptors in regulation of the cellular responses to glutamate
      challenge. Identification of the intracellular signals that trigger the glutamate
      induced self-protective mechanism would shed light on the genetic balance needed
      for survival, and guide the development of drugs for the up-regulation of desired
      genes and their products.

PMID- 11284555
TI  - Gray matter of the bovine cervical spinal cord is mechanically more rigid and
      fragile than the white matter.
AB  - The gray matter of the cervical spinal cord has been thought to be equally or
      less rigid than the white matter. Based on this assumption, various studies have
      been conducted on the changes of stress distributions within the spinal cord
      under mechanical compression, although the mechanical properties of the white and
      gray matters had not been fully elucidated. The present study measured the
      mechanical properties of the white and gray matter of bovine spinal cords. For
      both the white and gray matter, the stress-strain curves had a nonlinear region,
      followed by a linear region, and then a region where the stresses plateaued
      before failure. In the nonlinear region, stress was not significantly different
      between the gray and white matter samples (strain approximately 0-10%), while
      stress and Young's modulus in the gray matter was significantly higher than the
      white matter in the linear part of the curve. The gray matter ruptured at lower
      strains than the white matter. These findings demonstrated the gray matter is
      more rigid and fragile than the white matter, and the conventional assumption
      (i.e., the white matter is more rigid than the gray matter) is not correct. We
      then applied our data to computer simulations using the finite element method,
      and confirmed that simulations agreed with actual magnetic resonance imaging
      findings of the spinal cord under compression. In future computer simulations,
      including finite element method using our data, changes in stress and strain
      within the cervical spinal cord under compression would be clarified in more
      detail, and our findings would also help to elucidate the area which can easily
      receive histologic damage or which could have hemodynamic disorders under
      mechanical compression, as well as severity and location of biochemical and
      molecular biological changes.

PMID- 11284554
TI  - Astrocytes produce and release interleukin-1, interleukin-6, tumor necrosis
      factor alpha and interferon-gamma following traumatic and metabolic injury.
AB  - The brain is no longer considered immune-privileged due to its capability of
      producing cytokines in response to neurotrauma; however, the cellular sources of
      cytokines have not been defined. This study focused on the production of four
      inflammatory cytokines, interleukin-1 (IL-1alpha), interleukin-6 (IL-6), tumor
      necrosis factor alpha (TNFalpha), and interferon gamma (IFN-gamma) in primary
      culture of astrocytes under two different injury models which simulated in vivo
      mechanical trauma (scratch injury) and ischemia. Results demonstrated that
      astrocytes after scratch injury were positively immunostained with IL-1alpha, IL
      6, and TNFalpha. A slot-blot study of culture media showed that the release of IL
      1alpha, IL-6, TNFalpha, and IFN-gamma by astrocytes subsequent to scratch and
      ischemic injury reached approximately twice the control values. The temporal
      expression of these cytokines was different for the two models. All four
      cytokines began to increase 1 h postscratch and remained at high levels
      throughout the experiment. In the ischemic model, however, the increase of
      cytokine expression was delayed until 4-8 h of ischemia, when sharp increases
      were seen in all four cytokines. In this culture system, the exogenous influence
      of blood-borne factors and leukocytes, which occur with in vivo trauma and
      ischemia, was eliminated. Accordingly, the cytokines detected in the culture
      media were derived from astrocytes. This study provides the first evidence that
      astrocytes, without the influence from other cell types, can produce and release
      cytokines following mechanical and ischemic injury.

PMID- 11284556
TI  - Current trends in the enhancement of fracture healing.

PMID- 11284557
TI  - 'Audits', trials, user groups and industry.

PMID- 11284558
TI  - A histological study of the necrotic area after transtrochanteric anterior
      rotational osteotomy for osteonecrosis of the femoral head.
AB  - We studied nine patients who had had a transtrochanteric anterior rotational
      osteotomy, as developed by Sugioka, for osteonecrosis of the femoral head. At a
      mean of 2.5 years after the initial operation we carried out a histological study
      of the previously necrotic femoral head which had not shown collapse of the new
      primary weight-bearing site. In seven joints, there was proliferation of fibrous
      tissue in the dead trabeculae with vascular ingrowth. New bone covering dead
      trabeculae created the characteristic appearance of 'creeping substitution'.
      However, these changes were limited and did not extend over the entire necrotic
      area. Dead bone remained in all the cases. In the other two heads we did not
      observe proliferation of fibrous tissue or vascular ingrowth, only dead
      trabeculae and dead bone marrow.

PMID- 11284559
TI  - Femoroacetabular impingement and the cam-effect. A MRI-based quantitative
      anatomical study of the femoral head-neck offset.
AB  - We have observed damage to the labrum as a result of repetitive acetabular
      impingement in non-dysplastic hips, in which the femoral neck appears to abut
      against the acetabular labrum and a non-spherical femoral head to press against
      the labrum and adjacent cartilage. In both mechanisms anatomical variations of
      the proximal femur may be a factor. We have measured the orientation of the
      femoral neck and the offset of the head at various circumferential positions,
      using MRI data from volunteers with no osteoarthritic changes on standard
      radiographs. Compared with the control subjects, paired for gender and age,
      patients showed a significant reduction in mean femoral anteversion and mean head
      neck offset on the anterior aspect of the neck. This was consistent with the site
      of symptomatic impingement in flexion and internal rotation, and with lesions of
      the adjacent rim. Furthermore, when stratified for gender and age, and compared
      with the control group, the mean femoral head-neck offset was significantly
      reduced in the lateral-to-anterior aspect of the neck for young men, and in the
      anterolateral-to-anterior aspect of the neck for older women. For patients
      suspected of having impingement of the rim, anatomical variations in the proximal
      femur should be considered as a possible cause.

PMID- 11284561
TI  - Fluconazole-impregnated beads in the management of fungal infection of prosthetic
      joints.
AB  - We report two cases of fungal infection of prosthetic joints which were
      successfully treated by the incorporation of fluconazole into
      polymethylmethacrylate beads inserted at the time of debridement.

PMID- 11284560
TI  - Harris Galante cementless acetabular replacement in avascular necrosis.
AB  - We describe the results of 76 total arthroplasties of the hip for stage-III or
      stage-IV avascular necrosis of the femoral head. Harris Galante Porous cups were
      used in 63 patients between 1986 and 1994 and followed prospectively. We reviewed
      70 hips with a follow-up of more than five years (mean 7.6). At the latest review
      the mean Harris Hip Score had improved from a preoperative value of 29 +/- 14.7
      to 94 +/- 6.8. Radiologically, there was no evidence of acetabular migration. The
      rate of revision for the femoral component was 8.6%, three being undertaken for
      loosening and three to allow downsizing of the femoral head. The rate of revision
      for the acetabular component was 7.1% (five cups). At the time of revision none
      of the cups was clinically loose, and only required the liner to be changed. The
      rate of complications was low with no case of deep infection or dislocation, but
      nine of the 76 hips (11.8%) showed grade-III heterotopic ossification. Previous
      studies of patients undergoing cemented total hip arthroplasty for the treatment
      of advanced avascular necrosis have indicated a high incidence of loosening of
      the acetabular component. Our findings show good medium-term results using the
      Harris Galante Porous cup for acetabular reconstruction, together with a variety
      of cemented femoral components, for the treatment of this difficult problem.

PMID- 11284562
TI  - A seven-year experience of data collection on the Insall-Burstein II total knee
      arthroplasty. A prospective study.
AB  - We describe a method of audit of a type of total knee replacement, including some
      details of the organisational difficulties of administering multicentre studies,
      and draw attention to how this can be done using industrial funding without
      prejudicing the study. This is a prospective record of 1439 patients who had an
      Insall-Burstein II (IBII) prosthesis implanted between 1990 and 1994. The data
      were collected using the American Knee Society scoring system. A method of
      storing radiographs digitally at low cost is also described. The results
      emphasise the need for the long-term collection of data on commonly used devices
      implanted by a cross-section of surgeons. We conclude that for most patients the
      IBII cemented, posteriorly stabilised, cruciate-substituting prosthesis will
      relieve pain and give excellent functional results throughout the patients'
      remaining years with a very small incidence of revision, except in cases of
      infection.

PMID- 11284563
TI  - Oxford medial unicompartmental knee arthroplasty. A survival analysis of an
      independent series.
AB  - We describe the outcome of a series of 124 Oxford meniscal-bearing
      unicompartmental arthroplasties carried out for osteoarthritis of the medial
      compartment. They had been undertaken more than ten years ago in a non-teaching
      hospital in Sweden by three surgeons. All the knees had an intact anterior
      cruciate ligament, a correctable varus deformity and full-thickness cartilage in
      the lateral compartment. Thirty-seven patients had died; the mean time since
      operation for the remainder was 12.5 years (10.1 to 15.6). Using the endpoint of
      revision for any cause, the outcome for every knee was established. Six had been
      revised (4.8%). At ten years there were 94 knees still at risk and the cumulative
      survival rate was 95.0% (95% confidence interval 90.8 to 99.3). This figure is
      similar to that reported by the designers of the prosthesis and to the best
      published results for independent series of total knee replacement. If patients
      are selected appropriately, this implant is a reliable treatment for anteromedial
      osteoarthritis of the knee.

PMID- 11284564
TI  - Movement of the knee in osteoarthritis. The use of electrogoniometry to assess
      function.
AB  - We used electrogoniometers to measure the range of movement (ROM) of the knee
      during various activities, comparing 50 patients with osteoarthritis of the knee
      (OA) with 20 healthy age- and sex-matched subjects. The minimum and maximum joint
      angles and the ranges of excursion of the patient and control groups were tested
      for significant differences, using an unrelated Student's t-test with pooled
      variance. Knee flexion in patients with OA was significantly reduced during all
      activities (p < 0.05), but differences in knee extension were not significant
      except when patients negotiated stairs. We believe that this reduction in ROM is
      caused by inhibition due to pain when load-bearing. Static non-load-bearing
      measurements of the ROM poorly reflected the functional ROM, with a coefficient
      of determination (r2) of 0.59 in the patient group and 0.60 in the control group.
      Electrogoniometry of the ROM of the knee provides a reliable, accurate and
      objective measurement of knee function.

PMID- 11284565
TI  - Tibiocalcaneal fusion for avascular necrosis of the talus.
AB  - Between 1994 and 1999, we treated six patients with avascular necrosis of the
      talus by excision of the necrotic body of the talus and tibiocalcaneal fusion
      using an Ilizarov frame. This was combined with corticotomy and a lengthening
      procedure. Shortening was corrected in all patients except two, who were over 60
      years of age. All patients had previous operations which had failed. All achieved
      solid bony fusion, with five out of six having either a good or an excellent
      result. We conclude that this is an effective reconstructive technique which
      gives a good functional result.

PMID- 11284566
TI  - 'Fat fracture'--a physical sign mimicking tendon rupture.
AB  - The imaging techniques available to aid the diagnosis of ruptures of tendo
      Achillis, the rotator cuff and the tendon of tibialis posterior in rheumatoid
      patients are well described. However, ruptures of tendon or muscle at other sites
      are uncommon and may be overlooked. Diagnosis is often made by localised
      tenderness, swelling and a lack of active movement associated with a palpable
      defect. Clinical examination may be inconclusive and can be aided by imaging
      studies. We report two cases in which ruptures of a tendon were suspected, and
      ultrasound imaging demonstrated the palpable defect to be a cleavage plane in the
      subcutaneous fat--a 'fat fracture'.

PMID- 11284567
TI  - Treatment for displaced intracapsular fracture of the proximal femur. A
      prospective, randomised trial in patients aged 65 to 79 years.
AB  - We performed a prospective, randomised trial comparing three treatments for
      displaced intracapsular fractures of the hip in 280 patients aged 65 to 79 years.
      The mean patient survival was significantly higher in the group undergoing
      reduction and internal fixation (79 months) compared with that with a cemented
      Thompson hemiarthroplasty or a cemented Monk bipolar hemiarthroplasty (61 months
      and 68 months, respectively). After three years, 32 of 93 patients (34.4%) who
      had undergone fixation had local complications, necessitating further
      intervention in 28 (30%). There were no significant differences in the functional
      outcome in survivors, who were reviewed annually to five years. Either reduction
      and internal fixation or cemented hemiarthroplasty may be offered as alternative
      treatments for a displaced intracapsular fracture in a mobile and mentally
      competent patient under the age of 80 years. The choice of procedure by the
      patient and the surgeon should be determined by the realisation that the use of
      internal fixation is associated with a 30% risk of failure requiring further
      surgery. If this is accepted, however, hemiarthroplasty is avoided, which, in our
      study has a significantly shorter mean survival time. The use of a bipolar
      prosthesis has no significant advantage.

PMID- 11284568
TI  - Cementless surface replacement arthroplasty of the shoulder. 5- to 10-year
      results with the Copeland mark-2 prosthesis.
AB  - Cementless surface replacement arthroplasty of the shoulder is designed to
      replace the damaged joint surfaces and restore normal anatomy with minimal
      resection of bone. We have used the Copeland shoulder arthroplasty for 14 years.
      Between 1986 and 2000, 285 surface replacement arthroplasties were implanted in
      our unit. The prosthesis has evolved during this time, but the principle of
      minimal bone resection has remained the same. Between 1990 and 1994, 103 Mark-2
      prostheses were inserted into 94 patients (9 bilateral). The operations were
      carried out for the treatment of osteoarthritis, rheumatoid arthritis, avascular
      necrosis, instability arthropathy, post-traumatic arthropathy and cuff
      arthropathy. The mean follow-up was for 6.8 years (5 to 10). The best results
      were achieved in primary osteoarthritis, with Constant scores of 93.7% for total
      shoulder replacement and 73.5% for hemiarthroplasty. The poorest results were
      seen in patients with cuff arthropathy and post-traumatic arthropathy with
      adjusted Constant scores of 61.3% and 62.7%, respectively. Most patients (93.9%)
      considered their shoulder to be much better or better than before the operation.
      Of the 88 humeral implants available for radiological review, 61 (69.3%) showed
      no evidence of radiolucency, nor did 21 (35.6%) of the 59 glenoid prostheses.
      Three were definitely loose, and eight shoulders required revision (7.7%), two
      (1.9%) for primary loosening. The results of this series are comparable with
      those for stemmed prostheses with a similar follow-up and case mix. The
      cementless surface replacement arthroplasty diminishes the risk of complications
      involving the humeral shaft and periprosthetic fractures. Revision or arthrodesis
      can be undertaken easily since the bone stock has been maintained with no loss of
      length.

PMID- 11284569
TI  - Tuberculosis of the craniocervical junction.
AB  - Tuberculosis of the craniocervical junction is rare even where the condition is
      endemic. It poses problems in both diagnosis and management. We describe 25 cases
      followed over a period of 12 years, and relate the presentation, diagnosis and
      management. Of our 25 patients 16 were managed conservatively and nine by
      surgery. In order to diagnose this condition a high index of suspicion and
      advanced imaging techniques are necessary. Early diagnosis and adequate treatment
      led to good results without fatal complications.

PMID- 11284570
TI  - Symptoms and signs of irritation of the brachial plexus in whiplash injuries.
AB  - We investigated the incidence of evidence of irritation of the brachial plexus in
      119 patients with whiplash injuries sustained in road-traffic accidents. We
      compared the symptoms, physical signs, autonomic status, psychological status and
      findings from radiographs of the cervical spine using examination charts and a
      modified Cornell Medical Index Health questionnaire, in patients in two distinct
      groups: those with irritation of the brachial plexus and those without. There
      were 45 patients (37.8%) in the first group. The ratio of women to men was
      significantly higher in patients with irritation of the plexus as was the
      incidence of symptoms other than neck pain. There was no significant difference
      between the two groups with regard to psychological status or findings in
      radiographs of the cervical spine. Symptoms and signs attributable to stretching
      of the brachial plexus do occur in a significant proportion of patients after a
      whiplash injury. Their presence and persistence are associated with a poor
      outcome.

PMID- 11284571
TI  - Fracture of the carpal scaphoid. A prospective, randomised 12-year follow-up
      comparing operative and conservative treatment.
AB  - We compared the long-term outcome in 61 patients (62 fractures) treated
      operatively or conservatively for an acute fracture of the carpal scaphoid. A
      total of 30 fractures was randomised to conservative treatment using a cast and
      32 to operative treatment using a Herbert bone screw. The duration of sick leave
      was shorter for patients treated by operation, but this was only significant in
      patients with blue-collar occupations. There were no differences between the
      groups in respect of function, radiological healing of the fracture, or carpal
      arthritis after follow-up at 12 years. Those managed by operation showed
      radiological signs of arthritis of the scaphotrapezial joint more often, but this
      finding did not correlate with subjective symptoms. Operative treatment of an
      acute fracture of the scaphoid allows early return of function and should be
      regarded as an alternative to conservative treatment in patients in whom
      immobilisation in a cast for three months is not acceptable for reasons related
      to sports, social life or work.

PMID- 11284572
TI  - Assessing the outcome of disorders of the hand. Is the patient evaluation measure
      reliable, valid, responsive and without bias?
AB  - The different attributes of the Patient Evaluation Measure (PEM) questionnaire
      were investigated in 80 patients with a fracture of the scaphoid. Assessments
      were made at 2, 8, 12, 26 and 52 weeks. Reliability was assessed by measurement
      of the internal consistency of the different questions in 275 completed PEM
      forms. Cronbach's alpha, which needs to lie between 0.7 and 0.9, was 0.9 for the
      PEM. Pain, tenderness, swelling, wrist movement and grip strength correlated with
      the PEM score confirming the validity of the assessment. Changes in the different
      variables between visits correlated significantly with changes in the PEM score;
      its effect size and standardised response mean were comparable to those of grip
      strength and movement, confirming the responsiveness of this questionnaire.
      Gender, dominance and the side injured did not influence the scores. Older
      patients had a poorer outcome as assessed by the score which appeared to be a
      true effect and not age bias. Our study confirmed that the PEM is a reliable,
      valid and responsive instrument in assessing outcomes of disorders of the hand.

PMID- 11284573
TI  - Compartmental divisions of the hand revisited. Rethinking the validity of cadaver
      infusion experiments.
AB  - The results of a cadaver dye-infusion experiment suggested that the hand has ten
      muscle compartments and that the volar interossei occupy a separate anatomical
      compartment from the adjacent dorsal interossei. This is not supported by
      clinical findings. With various minor modifications, we repeated the experiment,
      infusing Omnipaque into the second dorsal interosseus muscle of four cadaver
      hands. We used real-time CT imaging to monitor the spread of contrast medium and
      side-ported needles to measure compartmental pressures. In all four hands, the
      tissue barrier between dorsal and volar interossei became incompetent at
      pressures of less than 15 mmHg. Our data indicate that, although cadaver infusion
      studies can delineate potentially significant musculoskeletal barriers, their
      physiological relevance must be confirmed clinically.

PMID- 11284574
TI  - The compartments of the foot revisited. Rethinking the validity of cadaver
      infusion experiments.
AB  - Previous dye-infusion experiments on cadavers have suggested that the hindfoot
      should be divided into four muscle compartments including a newly described
      'calcaneal' element containing quadratus plantae. Since there are no clinical
      data to support this proposed division, we re-examined the validity of the
      infusion experiment. We made infusions of dilute Omnipaque at a constant rate
      into flexor digitorum brevis of four cadaver feet. We monitored the spread of the
      infusate by real-time CT imaging and measured the pressures at the infusion site
      by side-ported needles. In all feet, the barrier between flexor digitorum brevis
      and quadratus plantae became incompetent at pressures of less than 10 mmHg.
      Pressure gradients in this range cannot be expected to affect tissue perfusion
      significantly and independently generate compartment syndromes. These results do
      not confirm those of previous studies carried out by uncontrolled and unmonitored
      injections made by hand. Injection studies in cadaver limbs can give dramatically
      different results depending upon the assumptions made when designing the
      experiment. The technique cannot adequately act as a model of the physiology of
      the compartment syndrome. As the existence of a physiologically significant
      compartmental boundary between flexor digitorum brevis and quadratus plantae is
      based solely on a cadaver infusion experiment the presence of a 'calcaneal'
      compartment has not been confirmed.

PMID- 11284575
TI  - The surgical anatomy of the dorsomedial cutaneous nerve of the hallux.
AB  - Most techniques described for the correction of hallux valgus require exposure of
      the distal aspect of the first metatarsal. A dorsomedial incision is often
      recommended. Texts counsel against damaging the dorsal digital nerve, as a
      painful neuroma is an unwelcome surgical complication. Our study on cadavers
      aimed to investigate the anatomy of the dorsomedial cutaneous nerve in the
      metatarsophalangeal region, with special reference to surgical incisions. A
      constant, previously unrecognised branch of the nerve was identified. This branch
      is likely to be damaged if a dorsomedial approach is used. It is recommended that
      a mid-medial incision be used instead, i.e. at the junction of the plantar and
      dorsal skin.

PMID- 11284576
TI  - Treatment of unstable fractures of the forearm in children. Is plating of a
      single bone adequate?
AB  - Unstable fractures of the forearm in children present problems in management and
      in the indications for operative treatment. In children, unlike adults, the
      fractures nearly always unite, and up to 10 degrees of angulation is usually
      considered to be acceptable. If surgical intervention is required the usual
      practice in the UK is to plate both bones as in an adult. We studied,
      retrospectively, 32 unstable fractures of the forearm in children treated by
      compression plating. Group A (20 children) had conventional plating of both
      forearm bones and group B (12 children) had plating of the ulna only. The mean
      age was 11 years in both groups and 23 (71%) of the fractures were in the
      midshaft. In group B an acceptable position of the radius was regarded as less
      than 10 degrees of angulation in both anteroposterior (AP) and lateral planes,
      and with the bone ends hitched. This was achieved by closed means in all except
      two cases, which were therefore included in group A. Union was achieved in all
      patients, the mean time being 9.8 weeks in group A and 11.5 weeks in B. After a
      mean interval of at least 12 months, 14 children in group A and nine in group B
      had their fixation devices removed. We analysed the results after the initial
      operation in all 32 children. The 23 who had the plate removed were assessed at
      final review. The results were graded on the ability to undertake physical
      activities and an objective assessment of loss of rotation of the forearm. In
      group A, complications were noted in eight patients (40%) after fixation and in
      six (42%) in relation to removal of the radial plate. No complications occurred
      in group B. The final range of movement and radiological appearance were compared
      in the two groups. There was a greater loss of pronation than supination in both.
      There was, however, no limitation of function in any patient and no difference in
      the degree of rotational loss between the two groups. The mean radiological
      angulation in both was less than 10 degrees in both AP and lateral views, which
      was consistent with satisfactory function. The final outcome for 23 patients was
      excellent or good in 12 of 14 (90%) in group A, despite the complications, and in
      eight of nine in group B (90%). If reduction and fixation of the fracture of the
      ulna alone restores acceptable alignment of the radius in unstable fractures of
      the forearm, operation on the radius can be avoided.

PMID- 11284577
TI  - Selective release of the flexor origin with transfer of flexor carpi ulnaris in
      cerebral palsy.
AB  - Transfer of flexor carpi ulnaris combined with selective release of the flexor
      pronator origin was undertaken in 35 patients with hemiplegic cerebral palsy for
      a pronation flexion deformity of the forearm, hand and wrist. The patients were
      divided into four groups depending on the severity of the deformity, the surgical
      procedure recommended, potential hand function and prognosis. The procedure
      reduces the power of wrist and finger flexion by release of the flexor pronator
      origin, and reinforces the strength of extension and supination of the wrist by
      transfer of flexor carpi ulnaris. After a mean follow-up of four years the
      appearance of the hand and forearm improved in all patients. None lost movement
      and all gained improved mobility of the forearm, wrist and hand. There was no
      overcorrection.

PMID- 11284578
TI  - Short stature as a screening test for endocrinopathy in slipped capital femoral
      epiphysis.
AB  - Slipped capital femoral epiphysis may be associated with hypothyroidism and other
      endocrinopathies. Routine screening for such abnormalities is unlikely to be cost
      effective since the overall incidence of these disorders, in association with
      slipped capital femoral epiphysis, is low. The identification of a presenting
      characteristic which would predict the chance of an associated endocrinopathy
      would allow only selected children to be screened. Our aim was to determine if
      certain characteristics were useful as a screen for patients with an underlying
      endocrinopathy who presented with slipped capital femoral epiphysis. Between
      January 1988 and December 1996 we recorded gender, age, height, unilateral or
      bilateral involvement and an associated diagnosis of endocrinopathy for all
      patients who were treated for slipped capital femoral epiphysis. Of 166 such
      patients 13 (7.8%) had an endocrinopathy. Height was the only useful screening
      characteristic, although bilateral involvement was more likely in those with an
      endocrinopathy. Most (90.9%) of this latter group were below the tenth percentile
      for height compared with only 5.4% in those who did not have an endocrinopathy (p
      < 0.005). The sensitivity and negative predictive value of detecting an
      underlying endocrinopathy in a patient presenting with a slipped capital femoral
      epiphysis and short stature (tenth percentile or less) were 90.2% and 98.6%,
      respectively. Patients who are on or below the tenth percentile for height at the
      time of presentation should be screened for a possible endocrine abnormality
      using measurement of thyroid-stimulating hormone and free thyroxine as a
      preliminary screening test. These hormones are most likely to be abnormal in the
      presence of endocrine dysfunction.

PMID- 11284579
TI  - Recurrent congenital haemangiopericytoma in a child.
AB  - A five-day-old boy was referred with a soft-tissue mass in his right upper arm.
      Plain radiographs and ultrasound demonstrated a lesion extending from the axilla
      to the elbow on the posterolateral aspect of the humerus. Open biopsy confirmed
      the diagnosis of congenital haemangiopericytoma. After MRI and selective
      angiography, excision biopsy was carried out, but no adjuvant therapy was
      administered. At further examination, four years and ten months later, he was
      noted to have three small nodules at the site of the original tumour. Excision
      biopsy confirmed this to be a local recurrence, although the lesion was less
      cellular with no appreciable mitotic activity. Congenital haemangiopericytoma is
      a rare cause of a soft-tissue mass in children. Most tumours are benign, and
      recurrence is uncommon. The treatment is controversial, but most centres
      recommend the use of adjuvant chemotherapy, combined with complete excision. We
      recommend treatment with doxorubicin. Orthopaedic surgeons should be familiar
      with this tumour since 30% to 50% of cases occur in the limbs.

PMID- 11284580
TI  - Selective reduction of bone blood flow by short-term treatment with high-dose
      methylprednisolone. An experimental study in pigs.
AB  - Treatment with corticosteroids is a risk factor for non-traumatic avascular
      necrosis of the femoral head, but the pathological mechanism is poorly
      understood. Short-term treatment with high doses of methylprednisolone is used in
      severe neurotrauma and after kidney and heart transplantation. We investigated
      the effect of such treatment on the pattern of perfusion of the femoral head and
      of bone in general in the pig. We allocated 15 immature pigs to treatment with
      high-dose methylprednisolone (20 mg/kg per day intramuscularly for three days,
      followed by 10 mg/kg intramuscularly for a further 11 days) and 15 to a control
      group. Perfusion of the systematically subdivided femoral head, proximal femur,
      acetabulum, humerus, and soft tissues was determined by the microsphere
      technique. Blood flow in bone was severely reduced in the steroid-treated group.
      The reduction of flow affected all the segments and the entire epiphysis of the
      femoral head. No changes in flow were found in non-osseous tissue. Short-term
      treatment with high-dose methylprednisolone causes reduction of osseous blood
      flow which may be the pathogenetic factor in the early stage of steroid-induced
      osteonecrosis.

PMID- 11284581
TI  - Inflammatory responses of human primary macrophages to particulate bone cements
      in vitro.
AB  - We have investigated whether the particle-stimulated release of inflammatory
      cytokines from human primary macrophages in vitro was dependent upon the type of
      bone cement used. Particles of clinically relevant size were produced from
      Palacos R without radio-opacifier, Palacos R with BaSO4, Palacos R with ZrO2 and
      from CMW3 which contains BaSO4. All four preparations produced significantly
      greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1
      beta than a negative control but there were no significant differences between
      them. The differences in the ability to stimulate bone resorption and in clinical
      performance between proprietary bone cements previously recorded are not
      explained by the release of the cytokines most commonly implicated in osteolysis.

PMID- 11284582
TI  - Measuring bone mineral density of the pelvis and proximal femur after total hip
      arthroplasty.
AB  - We aimed to evaluate the precision and longitudinal sensitivity of measurement of
      bone mineral density (BMD) in the pelvis and to determine the effect of bone
      cement on the measurement of BMD in femoral regions of interest (ROI) after total
      hip arthroplasty (THA). A series of 29 patients had duplicate dual-energy x-ray
      absorptiometry (DXA) scans of the hip within 13 months of THA. Pelvic analyses
      using 3- and 4-ROI models gave a coefficient of variation (CV) of 2.5% to 3.6%
      and of 2.5% to 4.8%, respectively. Repeat scans in 17 subjects one year later
      showed a significant change in BMD in three regions using the 4-ROI model,
      compared with change in only one region with the 3-ROI model (p < 0.05). Manual
      exclusion of cement from femoral ROIs increased the net CV from 1.6% to 3.6% (p =
      0.001), and decreased the measured BMD by 20% (t = 12.1, p < 0.001). Studies of
      two cement phantoms in vitro showed a small downward drift in bone cement BMD
      giving a measurement error of less than 0.03 g/cm2/year associated with inclusion
      of cement in femoral ROIs. Changes in pelvic periprosthetic BMD are best detected
      using a 4-ROI model. Analysis of femoral ROI is more precise without exclusion of
      cement although an awareness of its effect on the measurement of the BMD is
      needed.

PMID- 11284583
TI  - Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells
      from bone marrow.
AB  - In 16 mature New Zealand white rabbits mesenchymal stem cells were aspirated from
      the bone marrow, cultured in monolayer and implanted on to a full-thickness
      osteochondral defect artificially made on the patellar groove of the same rabbit.
      A further 13 rabbits served as a control group. The rabbits were killed after 14
      weeks. Healing of the defect was investigated histologically using haematoxylin
      and eosin and Safranin-O staining and with immunohistochemical staining for type
      II collagen. We also used a reverse transcription-polymerase chain reaction (RT
      PCR) to detect mRNA of type-I and type-II collagen. The semiquantitative
      histological scores were significantly higher in the experimental group than in
      the control group (p < 0.05). In the experimental group immunohistochemical
      staining on newly formed cartilage was more intense for type-II collagen in the
      matrix and RT-PCR from regenerated cartilage detected mRNA for type-II collagen
      in mature chondrocytes. These findings suggest that repair of cartilage defects
      can be enhanced by the implantation of cultured mesenchymal stem cells.

PMID- 11284584
TI  - Strain distribution in the proximal human femur. An in vitro comparison in the
      intact femur and after insertion of reference and experimental femoral stems.
AB  - Six pairs of human cadaver femora were divided equally into two groups one of
      which received a non-cemented reference implant and the other a very short non
      dependent experimental implant. Thirteen strain-gauge rosettes were attached to
      the external surface of each specimen and, during application of combined axial
      and torsional loads to the femoral head, the strains in both groups were
      measured. After the insertion of a non-cemented femoral component, the normal
      pattern of a progressive proximal-to-distal increase in strains was similar to
      that in the intact femur and the strain was maximum near the tip of the
      prosthesis. On the medial and lateral aspects of the proximal femur, the strains
      were greatly reduced after implantation of both types of implant. The pattern and
      magnitude of the strains, however, were closer to those in the intact femur after
      insertion of the experimental stem than in the reference stem. On the anterior
      and posterior aspects of the femur, implantation of both types of stem led to
      increased principal strains E1, E2 and E3. This was most pronounced for the
      experimental stem. Our findings suggest that the experimental stem, which has a
      more anatomical proximal fit without having a distal stem and cortex contact, can
      provide immediate postoperative stability. Pure proximal loading by the
      experimental stem in the metaphysis, reduction of excessive bending stiffness of
      the stem by tapering and the absence of contact between the stem and the distal
      cortex may reduce stress shielding, bone resorption and thigh pain.

PMID- 11284585
TI  - Report of the 2000 ABC Travelling Fellows.

PMID- 11284586
TI  - The teaching of trauma and orthopaedic surgery to the undergraduate in the United
      Kingdom.

PMID- 11284587
TI  - The outcome of treatment of trigger thumb in children.

PMID- 11284588
TI  - Nonunion of the femoral diaphysis.

PMID- 11284589
TI  - Relapse in staged surgery for congenital talipes equinovarus.

PMID- 11284590
TI  - Fix and flap: the radical orthopaedic and plastic treatment of severe open
      fractures of the tibia.

PMID- 11284591
TI  - Triplane fractures of the distal tibia.

PMID- 11284592
TI  - Stress fracture of the fifth metatarsal.

PMID- 11284593
TI  - Distal biceps repair: a consistent and safe approach to the radial tuberosity.

PMID- 11284594
TI  - The effects of severe femoral bone loss on the flexion extension joint space in
      revision total knee arthroplasty: a cadaveric analysis and clinical consequences.
AB  - Five revision total knee arthroplasties (TKAs) involving severe femoral bone loss
      were performed in 1994. Each had sufficiently severe femoral bone loss in which
      collateral ligament origins and posterior capsular attachments were violated. A
      paradoxical phenomenon was observed in each case. Unlike primary TKAs, in which
      larger distal femoral bone resection leads to laxity of the knee joint in
      extension, these cases with severe distal femoral bone loss, after initial
      component selection, developed the opposite situation, a flexion contracture. It
      was hypothesized that femoral bone loss involving collateral ligament origins
      would permit distraction of the tibia below the femur with the knee held in
      flexion, but when the knee was brought to full extension, intact posterior
      structures would maintain a normal tibial position. To investigate this
      hypothesis, six fresh-frozen cadaveric lower limbs were tested in full extension
      and 45 degrees and 90 degrees of flexion after release of the femoral attachments
      of the collateral ligaments and the posterior capsule from the femur. Joint space
      changes were measured via a motion tracking device. Results showed that with loss
      of collateral attachments, 17.2+/-8.9 mm of joint space is created in 90 degrees
      of flexion, whereas the joint space in full extension is conserved (1.5+/-1.7
      mm). With additional loss of the posterior capsule, the joint space at 90 degrees
      of flexion increased to 26.2+/-6.1 mm, with minimal changes in the extension gap
      (3.4+/-0.8 mm). Distal femoral bone loss was associated with an increase in the
      flexion gap compared to the extension gap.

PMID- 11284595
TI  - Long-term results after operative treatment of femoral neck fractures with
      ceramic head prostheses.
AB  - From 1985-1990, a total of 277 elderly patients underwent hemiarthroplasty using
      a ceramic head prosthesis. Average patient age was 81.7 years. Of these, 77
      patients were available for follow-up examination in 1993. A standardized score
      was calculated assessing activity, gait, and hip pain; the average score was 58
      out of 78 possible points. Three patients had hip pain, and in 4 patients,
      radiographic examination revealed protrusio acetabuli. Two of 4 patients
      underwent revision surgery for replacement of the cup, leaving the stem in situ.
      Because of the small number of prosthetic-related complications, hemiarthroplasty
      using a ceramic head prosthesis is the recommended surgical treatment for femoral
      neck fractures in elderly patients. In the rare patient with protrusio acetabuli,
      revision surgery can be performed to replace the cup, leaving the stem in situ.

PMID- 11284596
TI  - Control of bone bleeding at the sternum and iliac crest donor sites using a
      collagen-based composite combined with autologous plasma: results of a randomized
      controlled trial.
AB  - In a randomized controlled trial, hemostatic effectiveness of a collagen-based
      composite (experimental group) was compared with standard hemostatic methods (ie,
      electrocautery and collagen sponge) (control group) at two bone sites. Hemostatic
      success, time to "controlled bleeding," and time to "complete hemostasis" were
      determined at the sternal edge following median sternotomy (n=64) and at the
      iliac crest following bone graft harvest (n=19). Almost twice the percentage of
      sternal edge patients (83% versus 44%, P=.002) and nearly three times the
      percentage of iliac crest patients (83% versus 29%, P<.05) achieved complete
      hemostasis in the experimental group compared to controls. Time to controlled
      bleeding and complete hemostasis for all bone sites also favored the experimental
      group over the control group at highly significant levels (P<.0001 for most
      comparisons). There were no adverse events related to experimental treatment use.
      The results support the use of this investigational hemostatic agent to control
      cancellous bone bleeding.

PMID- 11284597
TI  - Treatment of lumbosacral radicular pain with epidural steroid injections.
AB  - Fifty patients with an average age of 47 years received epidural steroid
      injections for lumbosacral radicular pain due to disk herniation or spinal
      stenosis. All patients had failed previous conservative treatment. Mean follow-up
      was 24 months (range: 12-36 months). Immediately after injection, all 50 patients
      reported various degrees of relief from leg and back pain. At the last follow-up
      examination, 68% of patients were asymptomatic, 20% had no change in preinjection
      radicular symptoms, and 12% had various degrees of relief. No significant
      correlation was found between pain relief, age, or number of injections. Early
      pain relief may be anticipated after epidural steroid injections in 80% of
      patients with radicular symptoms due to disk herniation or spinal stenosis.

PMID- 11284598
TI  - Evaluation of knee consultations to a referral-only orthopedic clinic in a
      managed care system.
AB  - One hundred sixty-five knee consultations to a referral-only orthopedic service
      over a 2-year period were reviewed to document the gatekeeper diagnosis and
      initial treatment plan. These data were compared to the orthopedic evaluation.
      The majority of gatekeeper referral diagnoses were nonspecific or inaccurate.
      Several misdiagnoses resulted in prolonged patient recovery (delayed quadriceps
      tendon repair) and reinjury (recurrent instability of unrecognized anterior
      cruciate ligament-deficient knees). These findings suggest the gatekeeper model
      may be inadequate to appropriately manage knee disorders.

PMID- 11284599
TI  - Use of a calcium sulfate-based bone graft substitute for benign bone lesions.
AB  - Twenty-three patients with a benign bone lesion grafted with calcium sulfate,
      with and without demineralized bone matrix, were reviewed. At a minimum of 1 year
      postoperatively, 21 patients had achieved between 76% and 100% bone repair based
      on anteroposterior and lateral radiographs. Overall, the mean Enneking Functional
      Evaluation System score was 98%. Calcium sulfate is a well-tolerated,
      biodegradable, osteoconductive bone graft substitute. It is a reasonable
      alternative to autogenous bone graft for benign bone lesions.

PMID- 11284600
TI  - Matched distal ulnar resection for chronic, traumatic volar dislocation of the
      distal radioulnar joint.

PMID- 11284601
TI  - Osteoid osteoma: an unusual cause of foot pain.

PMID- 11284602
TI  - Osteolytic reaction to polylevolactic acid fracture fixation.

PMID- 11284603
TI  - Implications of hip subluxation for FES-assisted mobility in patients with spinal
      cord injury.

PMID- 11284604
TI  - Use of percutaneous drain insertion in the management of advanced pyomyositis.

PMID- 11284605
TI  - The use of biologic materials in spinal fusion.

PMID- 11284606
TI  - Electrical stimulation and lumbar spinal fusion.

PMID- 11284607
TI  - Recognizing and preventing adverse drug reactions: with particular reference to
      drug eruptions.

PMID- 11284608
TI  - Medicine in the digital era--opportunities and challenges.

PMID- 11284609
TI  - Drug eruptions in children: a review of 111 cases seen in a tertiary skin
      referral centre.

PMID- 11284610
TI  - A comparison of the maintenance and recovery charcateristic of sevoflurane
      nitrous oxide against isoflurane-nitrous oxide anaesthesia.
AB  - BACKGROUND: To compare the maintenance and recovery characteristics of
      sevoflurane and isoflurane anaesthesia in Malaysian patients. METHOD: This is a
      prospective, open labelled, randomized, controlled study. Sixty unpremedicated
      ASA I or II patients (aged 18-50 years), scheduled for elective breast lump
      excision were randomly allocated to receive either isoflurane or sevoflurane for
      the maintenance of anaesthesia following fentanyl and propofol intravenous
      induction. The systolic, diastolic, mean arterial blood pressure and heart rate
      were measured. The speed of recovery was measured by time to eye opening, time to
      following simple command, and time to correctly giving own names and address. The
      incidence of postoperative complication was also recorded. RESULTS: The trend of
      systolic blood pressure was significantly higher in the isoflurane group as
      compared to the sevoflurane group for the duration of anaesthesia (p < 0.001, by
      ANOVA for repeated measurement) but the trend of heart rate was similar for both
      groups. The recovery time was faster in the isoflurane group. [mean time of eye
      opening (SD) = 6.8 (2.2) vs 10.7 (4.4) min, p < 0.001; mean time of sticking
      tongue out (SD) = 7.9 (2.9) vs 11.5 (4.7) min, p < 0.01; mean time of giving own
      name (SD) = 7.8 (2.7) vs 11.8 (4.8) min, p < 0.001, mean time of giving own
      address (SD) = 8.4 (2.9) vs 12.0 (4.7) min, p < 0.01]. No major adverse effects
      were encountered postoperatively and the incidences of minor adverse effects were
      low in both groups. CONCLUSION: We concluded that sevoflurane is a safe
      alternative to isoflurane but in these short procedures, awakening time was
      surprisingly slower than after isoflurane.

PMID- 11284611
TI  - The orthotic management of the congenitally short lower limb--a new appliance.
AB  - AIM: To describe an appliance used for equalisation of severe congenital lower
      limb length discrepancy for patients who refuse to undergo any operative
      correction but wish to walk and look better. METHOD: The appliance which is a
      combination of an ischial bearing brace and a below knee prosthesis was fitted to
      four patients, aged between 12 and 31 years, with congenital shortening of the
      lower limb ranging between 17 to 27 centimetres. The diagnosis was proximal
      femoral focal deficiency in 2 patients, hypoplastic femur in 1 and tibial
      hemimelia in the fourth patient. The appliance could accommodate existing
      deformities of the knee, ankle and foot without any operative correction as well
      as equalise the lower limb length. It is modular in construction and could be
      easily assembled from off-the-shelf components. RESULT: The appliance improves
      the gait as well as the appearance, could be fitted to the patient without the
      prior need of operative correction and could be well disguised under any loose
      fitting garment. Four patients with severe congenital shortening of the leg have
      used it for over three years and are pleased with it. It requires little
      maintenance. CONCLUSION: The appliance is useful for patients with severe
      congenital shortening of the lower limb who refuse to undergo operative
      correction.

PMID- 11284612
TI  - Questionnaire survey on management of spontaneous pneumothorax.
AB  - INTRODUCTION: Management of spontaneous pneumothorax (SP) is variable and the
      initial management of SP is often undertaken by frontline junior medical staff.
      OBJECTIVES: To assess if medical education in the principles of SP management is
      adequate and to determine if practice variability exists among different
      disciplines. METHODS: A validated questionnaire survey on the knowledge and
      practice of the junior medical staff posted to a general hospital from May to
      December 1998 was performed. 138 doctors posted to the various departments:
      medical (n = S9), surgical (n = 46) and emergency (n = 33) were surveyed.
      RESULTS: The response rate was 95%. 73% surveyed had experience inserting chest
      tubes (CT). Of the 27% (n = 37) who had never inserted CT, 41% were medical
      officers. Our results showed adequate knowledge pertaining to initial management
      of primary SP (PSP). The preferred site and method for CT insertion was the 5th
      intercostal space, anterior axillary line and open method. There was significant
      practice variability in the CT size, method of insertion and CT removal sequence
      among the disciplines (p < 0.05). However a significant proportion of staff (49%)
      chose to observe or aspirate an acutely breathless patient with a 10% secondary
      SP (SSP) instead of CT insertion. CONCLUSION: While knowledge in PSP appears
      adequate, management of SSP and practical training in CT insertion must be
      emphasized as it is a simple procedure that is potentially life-saving.

PMID- 11284613
TI  - Beliefs about outcomes for mental disorders: a comparative study of primary
      health practitioners and psychiatrists in Singapore.
AB  - OBJECTIVES: To compare responses to a mental health literacy survey assessing the
      likely outcome of three major mental disorders by primary health practitioners
      (OPD doctors and GPs) and by psychiatrists in Singapore. METHODS: We used two
      vignettes of Major Depression and Schizophrenia developed in an Australian study.
      In addition, a third vignette of Mania was developed locally and included. The
      respondents were required to choose one of the set of prognostic options if the
      patients received or did not receive professional help, to rate the likely impact
      of the disorder, and to assess the likelihood of the patient being discriminated
      against. Psychiatrists' responses were obtained by surveying staff at Woodbridge
      Hospital, while the primary health practitioners were required to respond to a
      postal survey. RESULTS: The response rate for the psychiatrists was 70% (69/99),
      while the Primary health practitioners had an overall response rate of 38%
      (264/691). The response from OPDs being 51% (77/151) and that of the GPs being
      35% (189/540). There was evidence of disorder specificity, with schizophrenia
      judged as having the worst outcome and depression the best outcome in response to
      treatment. There was also evidence of group specificity, with the psychiatrists
      most optimistic and the OPD doctors least optimistic about the outcome following
      professional intervention. The majority of both the primary health practitioners
      and the psychiatrists judged that patients would be discriminated against, more
      so for schizophrenia and mania than for depression. Compared to the OPD doctors,
      a lower percentage of GPs felt that the patients would be discriminated against.
      CONCLUSION: Primary health practitioners in Singapore hold more negative views
      than Singapore psychiatrists about the outcome of professional intervention for
      three major psychiatric disorders. This finding has implications for education
      and training for primary health practitioners as well as for treatment of
      psychiatric patients in the primary health setting.

PMID- 11284614
TI  - Chylothorax after repair of congenital diaphragmatic hernia--a case report.
AB  - Chylothorax is a rarely recognised post-operative complication following repair
      of congenital diaphragmatic hernia. We report here a newborn infant with this
      condition which resolved with percutaneous chest drainage, total parenteral
      nutrition and enteral feeding of a formula high in medium-chain triglycerides.

PMID- 11284615
TI  - A case series of acanthamoeba keratitis in Singapore.
AB  - Acanthamoeba keratitis has become an important cause of severe ocular
      inflammation and visual loss in the past two decades. Its prevalence has been
      linked to the increasing use of contact lens. Early diagnosis, effective
      treatment regimes and education on proper contact lens wear are important in the
      management and prevention of visual loss from this debilitating disease. We
      described a series of two cases of culture positive acanthamoeba keratitis and
      their subsequent management.

PMID- 11284616
TI  - A case report on vesico-uterine fistula: a very rare complication of the lower
      caesarean section.
AB  - Vesico-uterine fistula is a very rare complication of lower caesarean section.
      There has only been two cases seen at the Department of Urology in the past 2
      decades. Patients usually present in the early post operative period with the
      problem of continuous urinary incontinence. On the rare occasion, recurrent
      urinary tract infection, recurrent gross painless haematuria, or secondary
      infertility associated with secondary amenorrhoea would be the presenting
      complaint.

PMID- 11284617
TI  - Clinics in diagnostic imaging (55). Ossification of the posterior longitudinal
      ligament.
AB  - Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine
      associated with diffuse idiopathic skeletal hyperostosis is described in a 70
      year-old Caucasian man presenting with a rapidly progressive myelopathy. The
      acute nature of his myelopathic symptoms and cervical canal stenosis necessitated
      posterior decompressive surgery. Four other patients with OPLL are presented to
      illustrate the spectrum of imaging findings. The computed tomographic features of
      OPLL are distinctive.A 2-5 mm thick linear ossified strip along the posterior
      vertebral margin usually at mid cervical (C3 to C5) level characterises the
      condition. Magnetic resonance (MR) imaging is valuable in excluding possible cord
      damage and associated disc lesions prior to surgery. A calcified central
      sequestrated disc is the only condition that may be mistaken for the segmental
      and retrodiscal forms of OPLL In a clinical setting of compressive myelopathy, it
      is pertinent to distinguish between these two conditions since a sequestrated
      disc has a more favourable surgical prognosis. The merits and relevance of
      anterior and posterior surgery together with their possible complications are
      outlined.

PMID- 11284618
TI  - Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: an
      international update.
AB  - Based on the results of two recent trials, docetaxel (Taxotere; Aventis, Antony,
      France) is now the drug of choice for the treatment of advanced non-small cell
      lung cancer that is refractory to primary chemotherapy. Trials are testing the
      role of docetaxel in the induction setting, as well as concomitantly with
      radiation therapy.

PMID- 11284619
TI  - Docetaxel (Taxotere) in combination with platinums in patients with non-small
      cell lung cancer: trial data and implications for clinical management.
AB  - Docetaxel (Taxotere; Aventis, Antony, France) is among the most effective agents
      for the treatment of non-small cell lung cancer and its use in combination with
      cisplatin is a logical development. Docetaxel has been combined with cisplatin
      and is well-tolerated with promising activity in phase II studies. Extensive
      phase II investigations in the first-line setting recorded response rates of 32%
      to 52% survival (median, 8 to 12 months) with 33% to 48% of patients alive at 1
      year. Neutropenia is dose-limiting. However, the incidence of severe neuropathy
      is low and clinically significant nephrotoxicity is uncommon. Following these
      encouraging findings, the combination of docetaxel with cisplatin has been
      studied in two randomized phase III trials that compare the new combination
      against reference regimens. These studies have completed accrual and data are
      expected shortly. The combination of docetaxel with carboplatin is also active
      and feasible. Neutropenia is the main adverse event and grade II or III
      neurotoxicity is uncommon. In phase II trials combining doses of 65 to 100 mg/m2
      docetaxel with doses of carboplatin designed to maintain an area under the curve
      of 5 to 7.5 mg/mL/min, response rates have ranged from 30% to 67%.

PMID- 11284620
TI  - Challenging the platinum combinations: docetaxel (Taxotere) combined with
      gemcitabine or vinorelbine in non-small cell lung cancer.
AB  - The limited single-agent activity of cisplatin, its toxicity profile, and the
      inconvenience involved in hydrating patients has compelled researchers to
      investigate other treatments as possible alternative therapies in non-small cell
      lung cancer. More recently, interest has focused on the potential of nonplatinum
      combinations. Phase II studies show that the combination of docetaxel (Taxotere;
      Aventis, Antony, France) and gemcitabine is active in stage IIIB/IV non-small
      cell lung cancer not previously treated by chemotherapy. Response rates of up to
      54% and a median survival time of 13 months have been reported. These data are
      comparable with the achievements of cisplatin-based combinations. A randomized
      phase II trial of docetaxel plus gemcitabine versus docetaxel plus cisplatin
      found that the two regimens were equally active in terms of response rate,
      median, and 1-year survival. However, the combination of docetaxel with
      gemcitabine produced significantly less neutropenia and nonhematologic
      toxicities. In combination, from 80% to 100% of the full single-agent gemcitabine
      and docetaxel doses can safely be administered once every 3 weeks. The
      combination of docetaxel plus vinorelbine is also active in non-small cell lung
      cancer and preliminary data suggest that this schedule with prophylactic
      filgrastim may optimize tolerability and dose intensity. In a phase II study
      using this approach, a confirmed response rate of 51% was obtained in 35
      patients. At 12 months, the predicted median survival is 14 months and the
      predicted 1-year survival rate is 60%. Excessive lacrimation, fatigue, and
      onycholysis were cumulative toxicities. However, the incidence of mucositis and
      neuropathy was low with the combination of docetaxel and vinorelbine. Docetaxel
      combined with other new agents, particularly gemcitabine, may offer another
      useful alternative to cisplatin-based chemotherapy in patients with good
      performance status.

PMID- 11284621
TI  - Docetaxel (Taxotere) in combination with radiation therapy and the potential of
      weekly administration in elderly and/or poor performance status patients with
      advanced non-small cell lung cancer.
AB  - A randomized phase II trial conducted by the Cancer and Leukemia Group B in
      patients with unresectable non-small cell lung cancer showed that induction
      chemotherapy followed by concurrent radiotherapy and chemotherapy was feasible
      when cisplatin was administered together with either gemcitabine, vinorelbine, or
      paclitaxel. The dominant toxicity was esophagitis. Preliminary survival data are
      encouraging. Other trials in progress or planned will elucidate the relative
      contributions of induction and concurrent therapy to outcome. A phase I study has
      shown that it is feasible to combine docetaxel (Taxotere: Aventis, Antony,
      France) with concomitant radiotherapy in patients with advanced non-small cell
      lung or esophageal cancer. Giving the drug once every 3 weeks during standard
      radiotherapy, the maximum tolerated dose is 40 mg/m2 per cycle. The dose-limiting
      toxicities are neutropenia and esophagitis. However, it is possible to escalate
      the total docetaxel dose to 60 mg/m2 per cycle by weekly administration of 20
      mg/m2. Beyond this point, esophagitis is dose limiting. In the palliative-intent
      treatment setting, the weekly administration of docetaxel is also likely to be a
      helpful new approach to administering the drug in subgroups of patients such as
      the elderly and those with concomitant disease. Weekly docetaxel (36 mg/m2/wk)
      was administered to patients with advanced non-small cell lung cancer who were
      elderly (median age, 71 years) or had poor performance status. In this
      unfavorable group, weekly docetaxel produced a 19% objective response rate and
      with further follow-up, 1-year survival is 28%. This level of activity is similar
      to other single agents recently evaluated in more favorable patient groups. The
      lack of myelosuppression seen with weekly administration suggests that the dose
      intensity of docetaxel could be maintained in combination regimens.

PMID- 11284622
TI  - Advances in the treatment of non-small cell lung cancer: molecular markers take
      the stage.
AB  - Increasing evidence that non-small cell lung cancer is a systemic disease from
      the outset confirms the rationale for adjuvant chemotherapy. However, clinical
      trial evidence of benefit is still awaited. The position is clearer in the case
      of neoadjuvant therapy because long-term follow up of two trials now shows that
      patients randomized to chemotherapy before surgery were significantly more likely
      to survive to 5 years than patients treated with surgery alone. Early data
      suggest that neoadjuvant chemotherapy based on docetaxel (Taxotere; Aventis,
      Antony, France) (possibly used sequentially with other agents) may be as
      effective as older regimens and better tolerated. Because p53 status influences
      the expression of microtubule-associated proteins and hence the sensitivity of a
      tumor to taxanes, it is possible that molecular markers could be used to
      customize chemotherapy to individual patients. Generally, it is becoming clearer
      that molecular staging is a more sensitive means of demonstrating tumor
      dissemination than light microscopy. The Cancer and Leukemia Group B is
      undertaking a prospective study using reverse transcriptase-polymerase chain
      reaction to detect MUC-1 RNA in bone marrow and hilar and mediastinal lymph nodes
      removed at resection with the aim of distinguishing between stage I patients
      likely to remain disease-free for long periods and those at high risk of relapse.
      A study of small cell lung cancer is using automated fluorescence microscopy to
      detect keratin-positive cells in the marrow and blood of patients who have a
      complete response to initial therapy but are nevertheless at high overall risk of
      relapse. The identification of genetic lesions in a high proportion of patients
      with non-small cell lung cancer may guide the development of new therapies aimed
      at increasing rates of apoptosis among tumor cells.

PMID- 11284623
TI  - Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second
      line treatment of non-small cell lung cancer: a review of two phase III trials.
AB  - The potential benefits of docetaxel (Taxotere; Aventis, Antony, France) to
      patients with previously-treated non-small cell lung cancer have been evaluated
      in two prospective randomized phase III trials. In one study, patients with stage
      IIIB/IV non-small cell lung cancer who had failed previous cisplatin-based
      chemotherapy were randomized to receive either docetaxel (100 or 75 mg/m2, once
      every 3 weeks) or best supportive care. Median survival was significantly longer
      for patients treated with docetaxel 75 mg/m2 (7.5 months v 4.6 months) as was 1
      year survival (37% v 11%). A second trial, also in platinum-pretreated patients,
      randomized patients to docetaxel 100 mg/m2, docetaxel 75 mg/m2, or
      vinorelbine/ifosfamide. Median survival was similar across the three study
      groups. Thirty-two percent of patients assigned to docetaxel 75 mg/m2 and 21% to
      docetaxel 100 mg/m2, were alive at 1 year, versus 19% on the
      vinorelbine/ifosfamide arm. Docetaxel offers clinically meaningful benefits in
      the second-line setting. The recommended dose is 75 mg/m2 once every 3 weeks. The
      adverse events observed were predictable, tolerable, and manageable. These phase
      III trials showed that docetaxel provided clinical benefits to patients with non
      small cell lung cancer.

PMID- 11284624
TI  - Quality of care and contraceptive pill discontinuation in rural Egypt.
AB  - Indicators of family planning service access and quality were generated using the
      Egypt DHS-I (1988) and the Egypt Service Availability Survey (1989), and linked
      to episodes of contraceptive pill use. Multilevel analysis was used to ascertain
      whether or not these access and quality indicators influence the continuation of
      pill use, net of women's socioeconomic, demographic and motivational
      characteristics. A model with random components at the cluster and women levels
      was fitted for all reasons of discontinuation, except desire for pregnancy, at 24
      months of use. Net of women's background characteristics, the results show that
      facilities with smaller numbers of health personnel trained in family planning, a
      lack of access to facilities with female doctors and a lack of range of available
      methods are associated with a high risk of discontinuation of pill use for all
      reasons except desire for pregnancy.

PMID- 11284625
TI  - Incidence and duration of romantic attraction in students progressing from
      secondary to tertiary education.
AB  - There is increasing interest in the nature and biological significance of
      romantic love but few quantitative data are available for testing specific
      hypotheses. This paper describes the use of a survey instrument to assess
      incidence and duration of romantic attractions over a 2-year period amongst
      students (121 male; 162 female) progressing from school to university education.
      The results for males and females were similar and schooling single-sex or co
      educational--had little effect. Students averaged 1.45 romantic episodes per year
      and 93% of students reported at least one episode over the survey period.
      Duration of attraction was around 9 weeks if never reciprocated and around 12
      weeks if reciprocated. There was seasonal variation of onset of episodes with
      peak incidence over the summer or early autumn seasons. Collectively the results
      accord with the view that frequent, short-duration romantic episodes could have a
      role in selection of appropriate long-term reproductive partnerships.

PMID- 11284626
TI  - Trends in consanguinity in South India.
AB  - This study uses data from the 1992-93 National Family Health Survey to assess
      trends in consanguinity in the South Indian states of Andhra Pradesh, Karnataka,
      Kerala and Tamil Nadu. In Kerala, the frequency of consanguineous marriages is
      very low and one type of preferred marriage of the Dravidian marriage system
      uncle niece marriage--is conspicuously absent. In the other states of South
      India, consanguinity and the coefficient of inbreeding are high. While no change
      in consanguinity is observed during the past three to four decades in Karnataka,
      a definite decline is observed in Andhra Pradesh and Tamil Nadu. Due to recent
      changes in the demographic and social situation in these states, this decline in
      consanguinity is likely to continue.

PMID- 11284627
TI  - Factors associated with unfavourable birth outcomes in Kenya.
AB  - Studies addressing factors associated with adverse birth outcomes have almost
      exclusively been based on hospital statistics. This is a serious limitation in
      developing countries where the majority of births do not occur within health
      facilities. This paper examines factors associated with premature deliveries,
      small baby's size at birth and Caesarean section deliveries in Kenya based on the
      1993 Kenya Demographic and Health Survey data. Due to the hierarchical nature of
      the data, the analysis uses multilevel logistic regression models to take into
      account the family and community effects. The results show that the odds of
      unfavourable birth outcomes are significantly higher for first births than for
      higher order births. Furthermore, antenatal care (measured by frequency of
      antenatal care visits and tetanus toxoid injection) is observed to have a
      negative association with the incidence of premature births. For the baby's size
      at birth, maternal nutritional status is observed to be a predominant factor.
      Short maternal stature is confirmed as a significant risk factor for Caesarean
      section deliveries. The observed higher odds of Caesarean section deliveries
      among women from households of high socioeconomic status are attributed to the
      expected association between socioeconomic status and the use of appropriate
      maternal health care services. The odds of unfavourable birth outcomes vary
      significantly between women. In addition, the odds of Caesarean section
      deliveries vary between districts, after taking into account the individual-level
      characteristics of the woman.

PMID- 11284628
TI  - Underlying and proximate determinants of diarrhoea-specific infant mortality
      rates among municipalities in the state of Ceara, north-east Brazil: an
      ecological study.
AB  - This ecological study examines the variations in diarrhoea-specific infant
      mortality rates among municipalities in the State of Ceara, north-east Brazil,
      using data from a community health workers' programme. Diarrhoea is the main
      cause of postneonatal deaths in Ceara, and diarrhoea mortality rates vary
      substantially among municipalities, from 7 to 50 per thousand live births. To
      determine the inter-relationships between potential predictors of diarrhoea
      specific infant mortality, eleven variables were classified into proximate
      determinants (i.e. adequate weight gain and exclusive breast-feeding in first 4
      months) and underlying determinants (i.e. health services and socioeconomic
      variables). The health services variables included percentage with prenatal care
      up-to-date, participation in growth monitoring and immunization up-to-date, while
      the socioeconomic factors included female illiteracy rate, per capita gross
      municipality product and percentage of households with low income, percentage of
      households with inadequate water supply and inadequate sanitation, and
      urbanization. Using linear regression analysis variables were included from each
      group to build regression models. The significant determinants of variability in
      diarrhoea-specific infant mortality between municipalities were prevalence of
      infants exclusively breast-feeding, percentage of infants with adequate weight
      gain, percentage of pregnant women with prenatal care up-to-date, female
      illiteracy rate and inadequate water supply. These findings suggest that
      community-based promotion of exclusive breast-feeding in the first 4 months and
      care-giving behaviours that prevent weight faltering, including weaning practices
      and feeding during and following diarrhoea episodes, may further reduce
      municipality-level diarrhoea-specific mortality. Primary heath care strategies
      addressing these two proximate determinants provide only a partial solution to
      reducing diarrhoeal disease mortality. Improvements in municipal health services
      (prenatal care) and socioeconomic status variables, including water supply and
      maternal education, can also contribute to reduction of infant mortality due to
      diarrhoea. These results may be used by government health officials to set
      priorities by considering not only the strength of the association between
      selected risk factors and diarrhoea mortality rates, but also the prevalence of
      the risk factors being considered at the municipality level. Finally, the methods
      used are applicable to other settings with community-based primary health care
      decentralized to the state or municipal level.

PMID- 11284629
TI  - The evolution of the family planning programme and its role in influencing
      fertility change in Kenya.
AB  - Kenya was one of the first sub-Saharan countries to enter the fertility
      transition, and analysts have suggested various explanations for this. This paper
      examines the growth in contraceptive availability in Kenya by looking at the
      Kenya family planning programme and its association with the fertility
      transition. This is of critical programmatic importance because the fertility
      transition is not yet underway in many sub-Saharan countries. Policymakers will
      find the information from this study helpful in evaluating the efficacy of
      current programmes and replicating the Kenyan programme in areas where fertility
      decline has not yet occurred. For researchers, the study attempts to highlight
      some of the major factors driving Kenya's fertility decline, apart from the
      conventional arguments about social and economic development.

PMID- 11284630
TI  - Variables that explain variation in prenatal care in Turkey; social class,
      education and ethnicity re-visited.
AB  - The extent and quality of prenatal care are important for the health of women and
      their babies. Recent studies suggest that women lack adequate prenatal care in
      contemporary Turkey. This paper uses regression models to examine the major
      factors impacting on the access of women to prenatal care through the 1993
      Turkish Demographic and Health Survey. The findings suggest that after
      controlling for class, ethnicity does not explain the likelihood of a woman's
      access to prenatal care, partly because the predominant patriarchal ideology in
      Turkey determines women's access to education, which in turn determines their
      access to prenatal care. It can be argued that unless women's socioeconomic
      status in the family improves, their access to health care in general and
      prenatal care in particular will not increase significantly.

PMID- 11284631
TI  - The effect of divorce on infant mortality in a remote area of Bangladesh.
AB  - The process of divorce is usually lengthy and hazardous, and can start quarrels
      that can lead to the abuse of women and their children. This study examines the
      effects of divorce on neonatal and postneonatal mortality of babies born before
      and after divorce in Teknaf, a remote area of Bangladesh. The longitudinal
      demographic surveillance system (DSS) followed 1,762 Muslim marriages in 1982-83
      for 5 years to record divorce, deaths of spouse, emigration and births. It
      recorded 2,696 live births during the follow-up period, and their survival status
      during infancy. Logistic regression models were used to estimate the effect of
      divorce on neonatal and postneonatal mortality, controlling for maternal age at
      birth, parity, sex of the child and household economic status. The odds of
      neonatal and postneonatal deaths among babies born after divorce or less than 12
      months before mothers were divorced were more than double the odds of those born
      to mothers of intact marriages. The odds of postneonatal deaths were two times
      higher among babies born more than 12 months before divorce happens than their
      peers. The high mortality of infants born before and after mothers were divorced
      may reflect how abusive marriage and divorce increase the vulnerability of women
      and children in rural Bangladesh. Divorce and abuse of women are difficult and
      intractable social and health problems that must be addressed.

PMID- 11284632
TI  - Long-term trends in marital status mortality differences in The Netherlands 1850
      1970.
AB  - This article describes the long-term trends in marital status mortality
      differences in the Netherlands using a unique dataset relating to the period 1850
      1970. Poisson regression analysis was applied to calculate relative mortality
      risks by marital status. For two periods, cause-of-death by marital status could
      be used. Clear differences in mortality by marital status were observed, with
      strongly increasing advantages for married men and women and a relative increase
      in the mortality of widowed compared with non-married people. Excess mortality
      among single and formerly married men and women was visible in many cause-of
      death categories, and this became more widespread during the last decades of the
      nineteenth century. Hypotheses are formulated that might explain why married men
      and women underwent a stronger decrease in mortality up until the end of World
      War II.

PMID- 11284633
TI  - Migration through surnames in Campobasso Province, Italy.
AB  - Data on grandparental surnames were obtained from school-children in 22 communes
      from Campobasso Province, Italy (Molise Region). The distribution of surnames was
      shown to be almost exactly linear by a log2-log2 transformation, which justified
      the fitting of the data to Fisher's logarithmic distribution. The values for v
      were higher among women. When v was standardized to minimize bias due to sample
      size, the value was one-third the estimate of migration from exogamy data. The
      higher values of v for females indicate that there is greater mobility of female
      marriage partners than males.

PMID- 11284634
TI  - Donor insemination in Israel: sociodemographic aspects.
AB  - The paper describes the sociodemography of donor insemination recipients in
      Israel. Arab recipients are very few. Among the Jews, married recipients are
      generally younger than their single counterparts, and they are somewhat less
      educated and more religious. Ethnically, the percentage of Orientals among the
      married recipients is relatively higher; among the single women, Orientals are
      under-represented. On the whole, however, donor insemination seems to have
      reached Jewish Israelis of all segments of society.

PMID- 11284635
TI  - Non-puerperal uterine inversion associated with an atypical leiomyoma.

PMID- 11284636
TI  - A case of ovarian stromal hyperplasia causing hirsutism in a post-menopausal
      woman.

PMID- 11284637
TI  - Iatrogenic pyocolpos in a young girl with imperforate hymen.

PMID- 11284638
TI  - Fallopian tube prolapse following abdominal hysterectomy.

PMID- 11284640
TI  - The management of endometrial carcinoma.

PMID- 11284639
TI  - Investigation and management of fetomaternal alloimmune thrombocytopenia.

PMID- 11284641
TI  - Differences and trends in obstetric interventions at term among urban and rural
      women in New South Wales: 1990-1997.
AB  - The aim of this study was to compare the management of term births among rural
      and urban women, including the effect of indigenous status and out-of-area-birth
      for rural women. Data were obtained from the NSW Midwives Data Collection (MDC),
      on 619,298 women who gave birth to a live, singleton infant at term (37-45 weeks
      gestation) from 1 January 1990 to 31 December 1997. Compared with urban non
      indigenous women, rural women and indigenous women had lower rates of obstetric
      interventions both before birth (induction of labour, planned Caesarean section
      and epidural) and at the time of birth (Caesarean after labour, instrumental
      delivery and episiotomy). This was especially true for rural women giving birth
      in the their local area. The differing pregnancy risk profile of rural women did
      not explain the differences in intervention rates but differences were partly
      explained by higher rates of epidural anaesthesia in urban areas.

PMID- 11284642
TI  - Seroprevalence of varicella zoster virus, parvovirus B19 and Toxoplasma gondii in
      a Melbourne obstetric population: implications for management.
AB  - At an antenatal clinic at a Melbourne obstetric hospital, 308 women were
      questioned about a known past history of infection with varicella zoster virus
      (VZV), human parvovirus B19 and Toxoplasma gondii. Immunoglobulin G (IgG)
      concentrations were determined for the 3 infectious agents and a recalled history
      of infection was compared with the presence of specific antibody. Exactly 66% of
      women recalled being infected with chickenpox (VZV) and 94% showed serological
      evidence of past exposure. Although 64% of women had parvovirus specific IgG,
      only one gave a definite history of past parvovirus infection. None of the 23% of
      women with evidence of previous exposure to Toxoplasma gondii recalled a past
      infection. The proportion of antenatal women at risk in this study was used to
      estimate the potential burden of disease from congenital infections in Australia
      and to examine implications for management of pregnancies complicated by these 3
      infections.

PMID- 11284643
TI  - Subsequent birth outcomes after an unexplained stillbirth: preliminary population
      based retrospective cohort study.
AB  - The objective of this study was to determine whether women who have experienced
      an unexplained stillbirth have a higher risk of adverse perinatal outcomes in
      subsequent births. We compared 316 subsequent births to women with a previous
      unexplained stillbirth, with 3160 births to women with no previous history of
      stillbirth, matched by year of birth, in the period 1987-1997, from the South
      Australian perinatal database, using logistic regression analysis. There was no
      increase in the rate of stillbirth and no statistically significant increase in
      the rate of perinatal death (OR 1.62 [95%CI 0.63-4.20]) or neonatal death,
      although larger studies are needed to confirm this. However, after adjusting for
      age, parity, and hospital category of birth, women who had a previous stillbirth
      had increased incidences in subsequent births of abnormal glucose tolerance or
      gestational diabetes (a fourfold increase); induction of labour and elective
      Caesarean section; fetal distress and postpartum haemorrhage; and forceps and
      emergency Caesarean delivery and preterm birth, which were independent of
      induction of labour. Gestational age at birth and birthweight were also
      significantly reduced, suggesting a need for close monitoring of their future
      pregnancies.

PMID- 11284644
TI  - Induction policy and missed post-term pregnancies: a mathematical model.
AB  - The aim of this study was to compare the clinical performance of ultrasound dates
      and ultrasound dates combined with menstrual dates for the detection of post
      maturity. A computer model was designed which uses the statistical distributions
      of the duration of normal pregnancy, day of ovulation in relation to the
      menstrual cycle and ultrasound error for estimating gestational age. The clinical
      performance of the different dating methods was then analysed from these
      variables, on simulations of 30,000 cases. The efficacy of different dating
      methods for detecting post-maturity was determined by generating receiver
      operator characteristics (ROC) curves. The proportion of post-term pregnancies
      (294 days and over) predicted by the model (3.5%) agrees with published values.
      There is a steep rise in missed cases if induction is delayed beyond 10 days from
      the expected date of delivery, reaching 20% on day 294. Elective delivery on day
      290 will detect 98.9% of cases destined to deliver post-term, with an induction
      rate of 10%; the respective figures for induction on day 294 are 79% and 3.8%.
      The ROC curves for the detection of post-maturity suggest that use of the mid
      trimester biparietal diameter (BPD) is better than a 7-day or 10-day rule. Timing
      of elective delivery is the most important variable affecting the detection rate
      for post-maturity There is no advantage in using menstrual dates when ultrasound
      biometry is available.

PMID- 11284645
TI  - Manual removal of the placenta--a case control study.
AB  - The aim of this study was to determine the incidence and complications related to
      manual removal of the placenta in a regional hospital in Australia. The study was
      carried out at the Goulburn Valley Base Hospital in Shepparton. The hospital
      medical records were reviewed from 1992 to 1999. A total of 3734 singleton live
      vaginal deliveries took place during the 7-year study period. The placenta was
      removed manually in 114 women (3%). For a control group, a series of 113 women
      who had singleton live vaginal deliveries from the same period were chosen at
      random. The case and control groups were similar in age, parity, and gravidity. A
      previous history of retained placenta and a history of preterm delivery in the
      current pregnancy were significantly related to retained placenta (OR 9.8 [95% CI
      1.1-85.5] and OR 5.6 [95% CI 1.1-26.8], respectively). The cases received
      significantly more blood transfusions than the control group (13% versus 0%).
      Decreased maternal age was also significantly related to retained placenta. There
      were also more post-delivery dilatation and curettage (D&C) operations and
      diagnosis of endomyometritis in the case group. However, these differences were
      not statistically significant. One woman, in the case group, had to have a
      hysterectomy due to placenta accreta.

PMID- 11284646
TI  - Feto-maternal alloimmune thrombocytopenia: a literature review and statistical
      analysis.
AB  - Exploring prognostic factors that determine outcomes in fetomaternal alloimmune
      thrombocytopenia (FMAIT), a search of Medline was performed covering the years
      1966 to April 1998. 376 articles were collected and reviewed; 140 articles
      contained the case histories of 297 mothers and 433 pregnancies that fulfilled
      entry criteria. More than 30 data variables were sought from these cases. The
      data were analysed using SPSS and Arcus Quickstat Biomedical. Nineteen different
      antigen incompatibilities were documented, the majority being human platelet
      antigen (HPA)-1a (77.3%), HPA-3a (3.5%) and HPA-5b (3.5%). The relative risk
      reduction (RRR) in mortality with any intervention was 57% (0.19-0.77) p = 0.009.
      Treatment of HPA-1a (PlA1) pregnancies with intravenous immunoglobulin (IVIG)
      increased the likelihood of a neurologically normal outcome, relative risk (RR)
      1.68, confidence interval (1.3-2.2) p = 0.0003. Treatment of HPA-1a (PlA1)
      pregnancies with only antenatal complementary platelet transfusions increased the
      likelihood of a neurologically normal outcome, RR 1.63 (1.1-2.1) p = 0.01.
      Despite reviews of more than 400 cases of FMAIT, few prognostic variables are
      identifiable. Although IVIG appears to reduce the risk of intracranial
      haemorrhage (ICH), the dosage and timing of IVIG treatment was varied. This study
      highlights the need for standardised and directed research.

PMID- 11284647
TI  - Abnormal uterine artery Doppler in small-for-gestational-age pregnancies is
      associated with later hypertension.
AB  - In a cohort of normotensive small-for-gestational-age (SGA) pregnancies, we aimed
      to determine the prevalence of later preeclampsia and gestational hypertension.
      We hypothesised that (i) uterine artery Doppler abnormalities would increase in
      severity from those with normotension to gestational hypertension to preeclampsia
      and (ii) the severity of uterine artery Doppler abnormalities would be related to
      the severity of fetal disease. Serial uterine and umbilical artery Doppler
      studies were performed on 224 normotensive women with SGA pregnancies, from
      detection of SGA until delivery. Outcomes were compared between groups that
      remained normotensive (n = 174) and those that developed gestational hypertension
      and preeclampsia. Of the women studied, 50 (22%) subsequently developed
      hypertension [(3% (n = 8) preeclampsia, 19% (n = 42) gestational hypertension)]
      at a median (interquartile range) of 19 (12-32) days after recognition of SGA.
      Mean uterine artery resistance indices (RI) increased from women who remained
      normotensive (n = 174) to those who later developed gestational hypertension or
      preeclampsia [0.51 (SD 0.09), 0.55 (0.09), 0.62 (0.13), p < 0.001], as did the
      proportion of abnormal uterine RI (33%, 39%, 88%, p = 0.007) and umbilical RI
      (28%, 40%, 75% p = 0.007). Mean uterine RI correlated negatively with z score
      birthweight (R2 = 0.069, p < 0.001) and positively with umbilical RI (R2 = 0.16,
      p < 0.001).

PMID- 11284648
TI  - A review of 165 cases of transvaginal sacrospinous colpopexy performed by the
      Endo Stitch technique.
AB  - The Endo Stitch technique has been in use in Geelong since 1994 as the method of
      performing transvaginal sacrospinous colpopexy (TSC). This article looks at the
      outcome of 165 of these procedures as assessed by a questionnaire. As the
      operation is technically easy, has a low complication rate and a high level of
      patient satisfaction we suggest that the Endo Stitch technique may be the method
      of choice for TSC.

PMID- 11284649
TI  - The current status of polycystic ovary syndrome.
AB  - The importance of polycystic ovary syndrome (PCOS) has recently received much
      publicity. Whereas previously it was thought simply to be a disorder which was
      characterised by irregular ovulation, there is now evidence to show that it is a
      systemic metabolic disease determined genetically and inherited. As well as
      treating the presenting problem which, for gynaecologists is usually one of
      irregular menstruation and anovulation, or sometimes signs of hyperandrogenism,
      we believe that women should also be screened for their lipid status and insulin
      resistance. Advice on behaviour modification such as increased exercise and
      dietary adjustment should be recommended in addition to the treatment for
      ovulation induction. In the future, the use of insulin sensitising agents may
      become important in the treatment of PCOS.

PMID- 11284650
TI  - Prognostic value of baseline serum oestradiol in controlled ovarian
      hyperstimulation of women with unexplained infertility.
AB  - This study aimed to evaluate the prognostic value of the baseline serum
      oestradiol E2 level on the cycle pregnancy rate (PR) in women with unexplained
      infertility (UI) undergoing controlled ovarian hyperstimulation (COH). This study
      is unique in that it evaluates the effect of cycle day 1 (rather than day 3) E2
      levels on cycle PR in a COH setting (without IVF) in women with UI (rather than
      multiple causes of infertility). Structured as a retrospective cohort study, the
      setting was the Ovulation Induction Clinic at an academic tertiary care hospital.
      One hundred and forty-five patients with UI underwent 374 cycles of COH with
      either human menopausal gonadotrophin (hMG) alone or hMG and clomiphene citrate.
      Outcome was measured as cycle pregnancy rate (PR) according to the cycle day 1
      level of E2. Patients with an E2 level > 150 pmol/l on cycle day 1 of COH
      achieved a significantly lower PR (4%) compared with those with E2 levels < or =
      150 pmol/l (13%). Logistic regression analysis demonstrated that women with day 1
      E2 levels below 150 pmol/l were 3.2 times more likely to conceive than those with
      day 1 E2 levels above 150 pmol/l. Also, the impact of day 1 E2 levels on the
      chance of pregnancy was independent of day 1 serum FSH levels. Women with UI
      undergoing COH in our unit with an elevated baseline serum E2 > 150 pmol/l have a
      significantly lower PR and should be counselled regarding the decreased
      likelihood of pregnancy.

PMID- 11284651
TI  - How long does it take to deliver a baby by emergency Caesarean section?
AB  - This audit documented the current range of decision-to-delivery reaction times
      for 464 emergency Caesarean sections performed in maternity hospitals with
      differing levels of facilities, and examined the reasons for any perceived delay.
      The median (with 10th-90th percentile) times from when the decision was made to
      perform an emergency Caesarean section to the delivery of the child were: 69 (37
      114), 54 (28-94) and 42 (17-86) minutes in Level 1, 2 and 3 maternity hospitals
      respectively when the indication for delivery was urgent. Less urgent emergency
      Caesarean sections took 70 (42-125), 66 (38-141) and 67 (35-164) minutes
      respectively. The main perceived reasons for delay in the delivery were staff
      unavailability in Level 1 hospitals, theatre access in Level 2 hospitals and
      anaesthetic complications in Level 3 hospitals. Therefore the decision-to
      delivery reaction times in the majority of urgent emergency Caesarean sections
      are, in practice, much longer than the times commonly advocated and are
      influenced by the facilities and staff available.

PMID- 11284652
TI  - Whole blood mercury concentrations in sub-fertile men in Hong Kong.
AB  - We aimed to investigate the association between whole blood mercury
      concentrations and semen quality in sub-fertile men. Fifty-nine male partners of
      infertile couples attending the Assisted Reproduction Unit of the Chinese
      University of Hong Kong between 1997 and 1998 were recruited into our study.
      Blood was taken from each subject for whole blood mercury concentration and
      hormone profile. Semen samples were obtained for computer assisted semen analysis
      using the Hobson sperm tracker. The semen parameters and hormone profile were
      compared between subjects with normal and those with elevated mercury
      concentrations. Twenty-one subjects (35.6%) had a whole blood mercury
      concentration higher than the normal range (0-50 nmol/l). All parameters of the
      semen analysis including the concentration of sperm, percentage of
      morphologically normal sperm, percentage of motile sperm, curvilinear velocity,
      straight-line velocity, average path velocity, and amplitude of lateral head
      displacement, were reduced in those with elevated blood mercury concentrations,
      although the difference was not statistically significant. We failed to
      demonstrate a statistically significant effect on the measurement of semen
      quality, but other adverse effects cannot be excluded. From a public heath
      perspective, these findings confirm that mercury toxicity is a potentially
      serious problem affecting the local community.

PMID- 11284653
TI  - Primary Bartholin gland carcinoma: a report of seven cases.
AB  - This study reviews our experience with 7 patients with primary Bartholin gland
      cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and
      compares this with previously published data. A retrospective clinicopathologic
      review of all patients with primary BGC treated at QCGC from 1988 to 2000 was
      performed. Of the 7 patients treated, all underwent primary surgery and 5 of the
      7 patients received radiotherapy postoperatively. All patients presented with a
      local swelling or a lump. Two had associated discharge and 2 had associated pain.
      Of the 7 patients, 2, 3 and 2 respectively were classified as having Stage IB, II
      or III disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had
      adenoid-cystic carcinoma and 1 had a small-cell neuroendocrine cancer of the
      Bartholin gland. None of the patients with SCC developed recurrent disease. The
      patient with adenoid-cystic carcinoma experienced local recurrences at 4 years
      and again at 5 years and 3 months. Nine years after primary treatment she was
      diagnosed with pulmonary metastases. The patient with small-cell neuroendocrine
      cancer of the Bartholin gland was considered tumour-free after operation.
      Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no
      evidence of disease. She died 1 year and three months after diagnosis from
      disseminated pulmonary disease. We present the first report of small cell
      neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the
      management of vulval cancer at other sites appear to be appropriate for
      management of BGC.

PMID- 11284654
TI  - Notification of Papanicolaou smear results: a survey of women's experiences and
      preferred means of notification.
AB  - In a population of Australian women attending a colposcopy clinic, we aimed to
      establish the method by which they were notified of their Pap smear result, who
      notified them of their result, and if given the choice, how they would prefer to
      be notified. Of women attending a colposcopy clinic between October 1998 and June
      1999, 59.7% participated in the survey. There was a final sample of 210 women
      after exclusion of questionnaires with missing data. The doctor most often
      notified women of their Pap smear result (81.7%). The usual methods of
      notification were by a follow-up appointment (43.1%), by a telephone call (35.8%)
      or with a letter (13.8%); 42% of women preferred to be notified with a mailed
      copy of the report and explanation of follow-up; 29.6% preferred to be telephoned
      with the result, and 11.3% would prefer a follow-up appointment. Women preferred
      methods of notification which were initiated by the doctor. Women have varying
      preferences, which commonly differ from the current services provided by both GPs
      and colposcopy clinic. To overcome this, women could be asked to nominate their
      preferred method of notification when completing the cervical smear request form.

PMID- 11284656
TI  - Attitudes of patients towards the involvement of medical students in their
      intrapartum obstetric care.
AB  - Data investigating patients' attitudes towards and expectations of medical
      students in an obstetric setting are limited. We have examined the attitudes of
      pregnant women towards the involvement of medical students in their intrapartum
      care. Ethics committee approval and informed patient consent were obtained. A
      survey of 203 antenatal patients was performed. Chi-squared tests were applied to
      discrete and Student's t-test to continuous data. Only 62% of antenatal patients
      were prepared to accept medical student participation in their intrapartum care,
      although 84% agreed that participation was important for student education. Of
      note, only 43% of patients were prepared to have a male medical student involved
      in their care. Only 54% of patients correctly identified that the description
      medical student referred to a doctor in training, others defining it to include
      nurses, midwives and other hospital staff in training. If increasing numbers of
      patients decline medical student participation in their intrapartum care, then
      alternative teaching strategies may be required. Medical educators need to ensure
      that patients are aware of the role of medical students in order to gain informed
      consent from patients for student participation in their care.

PMID- 11284655
TI  - Guideline use for gestational diabetes mellitus and current screening, diagnostic
      and management practices in Australian hospitals.
AB  - A postal questionnaire investigating screening, diagnosis and management
      practices for gestational diabetes mellitus (GDM) and guidelines use for GDM, was
      sent to 544 Australian hospitals providing maternity care. Of these, 360 (66%)
      responded. Guidelines for GDM were available in 127 (39%) hospitals. Screening
      for GDM was undertaken by 284 (87%) hospitals and of these, 151 (53%) screened
      all women and 63 (22%) selectively screened women. Half (143, 50%) of the
      hospitals surveyed screened women using a 50 g oral glucose challenge test (OGCT)
      and 70 hospitals (25%) used a 75 g OGCT. A 75 g oral glucose tolerance test was
      most commonly used to diagnose GDM (207; 81%) and 126 hospitals (60%) recommended
      a 2 hour blood glucose level of > or = 8.0 mmol/l as diagnostic for GDM. In the
      management of women with GDM, levels for optimal glycaemic control varied.
      Postpartum testing for diabetes mellitus was recommended by the majority of
      hospitals (202; 72%). This study has shown the majority of Australian hospitals
      providing maternity care screening for GDM, but there is little consensus in
      screening practices.

PMID- 11284657
TI  - Vaginal adenosis with adenocarcinoma in situ in a woman with no recognised
      antecedent factors.
AB  - We present a case of vaginal adenosis with adenocarcinoma in situ in a woman with
      no recognised antecedent factors. This case demonstrates the importance of
      continuing thorough colposcopic assessment of the entire lower genital tract with
      repeated biopsies of all abnormal epithelium in women with persistent or
      recurrent cervical cytology abnormalities. Successful management requires
      accurate definition of the vaginal lesion.

PMID- 11284658
TI  - Human reproductive failure I: immunological factors.
AB  - Human reproductive failure may be a consequence of aberrant expression of
      immunological factors during pregnancy. Although the relative importance of
      immunological factors in human reproduction remains controversial, substantial
      evidence suggests that human leukocyte antigens (HLA), antisperm antibodies,
      integrins, the leukaemia inhibitory factor (LIF), cytokines, antiphospholipid
      antibodies, endometrial adhesion factors, mucins (MUC1) and uterine natural
      killer cells contribute to reproductive failure. In contrast, fewer data support
      the roles of anti-trophoblast antibodies, anti-endometrial antibodies, T-cells,
      peripheral natural killer cells, anti-HLA antibodies, blocking antibodies and
      suppressor cells in reproductive failure. Although immunological factors involved
      in reproductive failure have been studied traditionally using assays for
      antibodies and/or antigens, detailed research on these factors demonstrates
      conflicting results in humans. Maternal and fetal immunology is also difficult to
      investigate in humans. For these reasons, molecular assays may serve as a
      valuable alternative to investigate how the immune system affects reproductive
      outcome. In Part I of this review, immunological factors involved in human
      reproductive failure are summarized and critically evaluated. Immunogenetic and
      interacting factors in human reproductive failure will be summarized and
      evaluated in Part II.

PMID- 11284659
TI  - Human reproductive failure II: immunogenetic and interacting factors.
AB  - Studies in humans suggest that reproductive failure may be influenced by
      immunological factors or by genes encoding immunological factors and regulatory
      mechanisms controlling immunological expression. Using molecular methods,
      immunological factors can be clearly studied in an immunogenetic context. One
      example, the major histocompatibility complex (MHC), known as the human leukocyte
      antigens (HLA) in humans and MHC in other mammals, affects many different stages
      of reproduction. Studies in some outbred, and in closely related, human
      populations indicate that HLA, or HLA-linked, genes and HLA regulatory factors
      affect gamete development, embryo cleavage, blastocyst and trophoblast formation,
      implantation, fetal development and survival. Studies in non-human mammals
      indicate that MHC, or MHC-linked, genes such as the grc complex, Ped/Qa-2, t
      haplotypes and MHC regulatory factors, have similar reproductive effects. Human
      reproductive failure may also be a consequence of disruption of interacting
      factors, including interactions between HLA antigens, cytokines and natural
      killer (NK) cells. In this review, we highlight the importance of immunogenetic
      and interacting factors in human reproductive failure. We argue that studies in
      closely related human populations and animal models may contribute to a better
      understanding of the ways in which immunogenetic and interacting factors are
      involved in human reproduction.

PMID- 11284660
TI  - Clinical implications of uterine malformations and hysteroscopic treatment
      results.
AB  - Uterine malformations consist of a group of miscellaneous congenital anomalies of
      the female genital system. Their mean prevalence in the general population and in
      the population of fertile women is approximately 4.3%, in infertile patients
      approximately 3.5% and in patients with recurrent pregnancy losses approximately
      13%. Septate uterus is the commonest uterine anomaly with a mean incidence of
      approximately 35% followed by bicornuate uterus (approximately 25%) and arcuate
      uterus (approximately 20%). It seems that malformed uterus and especially septate
      uterus is not an infertility factor in itself. However, it may have a part in the
      delayed natural conception of women with mainly secondary infertility. On the
      other hand, patients with uterine malformations seem to have an impaired
      pregnancy outcome even as early as their first pregnancy. Overall term delivery
      rates in patients with untreated uterine malformations are only approximately 50%
      and obstetric complications are more frequent. Unicornuate and didelphys uterus
      have term delivery rates of approximately 45%, and the pregnancy outcome of
      patients with untreated bicornuate and septate uterus is also poor with term
      delivery rates of only approximately 40%. Arcuate uterus is associated with a
      slightly better but still impaired pregnancy outcome with term delivery rates of
      approximately 65%. Women who have undergone hysteroscopic septum resection and
      have been reported in the different series comprise a highly selected group of
      symptomatic patients with term delivery and live birth rates of only
      approximately 5%. Hysteroscopic treatment seems to restore an almost normal
      prognosis for the outcome of their pregnancies with term delivery rates of
      approximately 75% and live birth rates of approximately 85%. It seems, therefore,
      that hysteroscopic septum resection can be applied as a therapeutic procedure in
      cases of symptomatic patients but also as a prophylactic procedure in
      asymptomatic patients in order to improve their chances for a successful
      delivery.

PMID- 11284661
TI  - Oxidative stress and protection against reactive oxygen species in the pre
      implantation embryo and its surroundings.
AB  - Oxidative stress is involved in the aetiology of defective embryo development.
      Reactive oxygen species (ROS) may originate from embryo metabolism and/or embryo
      surroundings. Embryo metabolism generates ROS via several enzymatic mechanisms.
      The relative contribution of each source seems different depending on the
      species, the stage of development, and the culture conditions. Several exogenous
      factors and culture conditions can enhance the production of ROS by embryos. ROS
      can alter most types of cellular molecules, and also induce development block and
      retardation. Multiple mechanisms of embryo protection against ROS exist, and
      these have complementary actions. External protection, present in follicular and
      tubal fluids, mainly comprises non-enzymatic antioxidants such as hypotaurine,
      taurine and ascorbic acid. Internal protection mainly comprises antioxidant
      enzymes: superoxide dismutase, glutathione peroxidase and gamma-glutamylcysteine
      synthetase. Transcripts encoding for these enzymes are present in the oocyte,
      embryo and oviduct. It may be important that these transcripts are stored during
      oocyte maturation in order to allow the embryo to acquire the aptitude to
      develop. It is now common to add antioxidant compounds to culture media.
      Nevertheless, maintaining the pro-oxidant-antioxidant equilibrium in embryos
      through such supplementation is a complex problem. Further studies are necessary
      to limit oxidative stress during embryo culture.

PMID- 11284662
TI  - Impact of genetic engineering on the understanding of spermatogenesis.
AB  - To date, about 100 genes have been found, by genetic engineering, to be
      implicated in spermatogenesis. Primordial germ cells, spermatogonia,
      spermatocytes I and elongating spermatids are particularly sensitive. Transgenic
      and knockout mice permit an approach to be made to the question of genetic
      factors involved in DNA damage repair, thermal injury, sperm chromatin compaction
      and sex-specific recombination. Knockout mice reveal unexpected functional
      redundancies of testis-specific genes. This review considers how functional
      divergences can exist among homologous genes from different species, and to what
      extent the phenotypes of knockout mice can be similar to those from spontaneous
      mutations. Additional anomalies in reproductive function have frequently been
      found in these mice, as were found factors leading to tumour susceptibility
      and/or various diseases. Finally, knockout mice remind us that, in nearly all
      cases, hemizygous individuals retain a fertility and a wild-type sperm phenotype,
      although half of the spermatozoa share a genetic defect. The findings strongly
      emphasize the importance of understanding epidemiology in male infertility, to
      identify hereditary forms of impaired spermatogenesis, and to create DNA and
      pathological germ cell banks.

PMID- 11284663
TI  - Epigenetic and experimental modifications in early mammalian development: part I.
      Preface.

PMID- 11284664
TI  - Mitochondria: potential roles in embryogenesis and nucleocytoplasmic transfer.
AB  - This review examines current understanding of mammalian mitochondria and
      mitochondrial DNA in the light of new reproductive technologies. Mitochondria are
      central to ageing, apoptosis, metabolism and many diseases. They are controlled
      by a dual genome system, with cooperation between endogenous mitochondrial genes
      and mitochondrial genes translocated to the nucleus over the course of evolution.
      This translocation has been accompanied by extreme compression of the
      mitochondrial genome, with little tolerance for mutations or heteroplasmy
      (multiple genomes). The highly compact mitochondrial genome appears to be
      maintained by a stringent numerical bottleneck in embryogenesis and oogenesis,
      followed by clonal expansion from a highly selected subset of precursor
      molecules. The dual nature of control between nucleus and cytoplasm sets up
      potential conflicts, which are normally resolved by natural selection. Such
      potentially opposing interests and mechanisms are probably partly to blame for
      the poor rates of success in cloning animals by nuclear transfer. The ability to
      construct cell systems and animal embryos with novel combinations and
      permutations of nuclear and cytoplasmic genes will provide powerful tools for
      examining these fundamental biological questions. Clinically, attempts to
      'rescue' abnormal human oocytes or embryos by cytoplasmic transfer risk complex
      and unpredictable outcomes emerging from disharmonious nuclear-cytoplasmic
      interactions.

PMID- 11284665
TI  - Factors influencing blood flow patterns in the human right coronary artery.
AB  - Evidence suggests that atherogenesis is linked to local hemodynamic factors such
      as wall shear stress. We investigated the velocity and wall shear stress patterns
      within a human right coronary artery (RCA), an important site of atherosclerotic
      lesion development. Emphasis was placed on evaluating the effect of flow waveform
      and inlet flow velocity profile on the hemodynamics in the proximal, medial, and
      distal arterial regions. Using the finite-element method, velocity and wall shear
      stress patterns in a rigid, anatomically realistic model of a human RCA were
      computed. Steady flow simulations (ReD=500) were performed with three different
      inlet velocity profiles; pulsatile flow simulations utilized two different flow
      waveforms (both with Womersley parameter=1.82, mean ReD=233), as well as two of
      the three inlet profiles. Velocity profiles showed Dean-like secondary flow
      features that were remarkably sensitive to the local curvature of the RCA model.
      Particularly noteworthy was the "rotation" of these Dean-like profiles, which
      produced large local variations in wall shear stress along the sidewalls of the
      RCA model. Changes in the inlet velocity profiles did not produce significant
      changes in the arterial velocity and wall shear stress patterns. Pulsatile flow
      simulations exhibited remarkably similar cycle-average wall shear stress
      distributions regardless of waveform and inlet velocity profile. The oscillatory
      shear index was very small and was attributed to flow reversal in the waveform,
      rather than separation. Cumulatively, these results illustrate that geometric
      effects (particularly local three-dimensional curvature) dominate RCA
      hemodynamics, implying that studies attempting to link hemodynamics with
      atherogenesis should replicate the patient-specific RCA geometry.

PMID- 11284666
TI  - Mass transport in an anatomically realistic human right coronary artery.
AB  - The coronary arteries are a common site of atherosclerotic plaque formation,
      which has been putatively linked to hemodynamic and mass transport patterns. The
      purpose of this paper was to study mass transport patterns in a human right
      coronary artery (RCA) model, focusing on the effects of local geometric features
      on mass transfer from blood to artery walls. Using a previously developed
      characteristic/finite element scheme for solving advection-dominated transport
      problems, mass transfer calculations were performed in a rigid, anatomically
      realistic model of a human RCA. A qualitative and quantitative examination of the
      RCA geometry was also carried out. The concentration field within the RCA was
      seen to closely follow primary and secondary flow features. Local variations in
      mass transfer patterns due to geometric features were significant and much larger
      in magnitude than local variations in wall shear stress. We conclude that the
      complex secondary flows in a realistic arterial model can produce very
      substantial local variations in blood-wall mass transfer rates, and may be
      important in atherogenesis. Further, RCA mass transfer patterns are more
      sensitive to local geometric features than are wall shear stress patterns.

PMID- 11284667
TI  - Validation of rapid velocity encoded cine imaging of a dynamically complex flow
      field using turbo block regional interpolation scheme for k space.
AB  - Block regional interpolation scheme for k space (BRISK) is a sparse sampling
      approach to allow rapid magnetic resonance imaging of dynamic events. Rapid
      velocity encoded cine (VEC) imaging with Turbo BRISK is potentially an important
      clinical diagnostic technique for cardiovascular diseases. Previously we applied
      BRISK and Turbo BRISK to imaging pulsatile flow in a straight tube. To evaluate
      the capabilities of Turbo BRISK imaging in more complex dynamic flow fields such
      as might exist in the human vasculature, an in vitro curved tube model, similar
      in geometry to the aortic arch, was fabricated and imaged under pulsatile flow
      conditions. Velocity maps were obtained using conventional VEC and Turbo BRISK
      (turbo factors 1 through 5). Comparison of the flow fields obtained with each
      higher order turbo factor showed excellent agreement with conventional VEC with
      minimal loss of information. Similarly, flow maps showed good agreement with the
      profiles from a laser Doppler velocimetry model. Turbo-5 BRISK, for example,
      allowed a 94% savings in imaging time, reducing the conventional imaging time
      from over 8 min to a near breath-hold imaging period of 31 s. Turbo BRISK shows
      excellent promise toward the development of a clinical tool to evaluate complex
      dynamic intravascular flow fields.

PMID- 11284668
TI  - Determination of blood flow velocity and transit time in cerebral arteriovenous
      malformation using microdroplet angiography.
AB  - Advancement in imaging and biomedical technology has improved the use of catheter
      based transarterial embolization (occlusive therapy) of cerebral arteriovenous
      malformations (AVMs). Among a variety of embolic agents, liquid adhesives
      (acrylates) have proven to be more successful in permanent obliteration of AVMs.
      The use of liquid adhesives requires the experience and skill of the operator.
      However, acquiring accurate information on blood flow and transit times through
      the AVM prior to embolization can optimize the treatment. In addition, knowledge
      of the polymerization time and behavior of the acrylate enables a complete and
      safe occlusion of the arteriovenous transition within the AVM nidus. Standard
      commercially available iodine-based contrast agents seem to be insufficient to
      determine AVM transit times from angiograms. For a more accurate assessment of
      AVM transit times, the use of a nonsoluble contrast agent (Ethiodol) and a high
      speed digital subtraction angiography (DSA) is suggested. Small amounts (<20
      microl) of Ethiodol were infused to create microdroplets and traced using DSA at
      15 fps. Transit time, defined as the time interval required for a droplet to
      reach the venous part of the AVM after being flushed from the tip of the
      catheter, could be accurately calculated. Postprocessing was used to calculate
      trajectories and velocities of microdroplets.

PMID- 11284669
TI  - Shear stress reduces protease activated receptor-1 expression in human
      endothelial cells.
AB  - Shear stress has been shown to regulate several genes involved in the thrombotic
      and proliferative functions of endothelial cells. Thrombin receptor (protease
      activated receptor-1: PAR-1) increases at sites of vascular injury, which
      suggests an important role for PAR-1 in vascular diseases. However, the effect of
      shear stress on PAR-1 expression has not been previously studied. This work
      investigates effects of shear stress on PAR-1 gene expression in both human
      umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells
      (HMECs). Cells were exposed to different shear stresses using a parallel plate
      flow system. Northern blot and flow cytometry analysis showed that shear stress
      down-regulated PAR-1 messenger RNA (mRNA) and protein levels in both HUVECs and
      HMECs but with different thresholds. Furthermore, shear-reduced PAR-1 mRNA was
      due to a decrease of transcription rate, not increased mRNA degradation.
      Postshear stress release of endothelin-1 in response to thrombin was reduced in
      HUVECs and HMECs. Moreover, inhibitors of potential signaling pathways applied
      during shear stress indicated mediation of the shear-decreased PAR-1 expression
      by protein kinases. In conclusion, shear stress exposure reduces PAR-1 gene
      expression in HMECs and HUVECs through a mechanism dependent in part on protein
      kinases, leading to altered endothelial cell functional responses to thrombin.

PMID- 11284670
TI  - Compressive deformation and damage of muscle cell subpopulations in a model
      system.
AB  - To study the effects of compressive straining on muscle cell deformation and
      damage an in vitro model system was developed. Myoblasts were seeded in agarose
      constructs and cultured in growth medium for 4 days. Subsequently, the cells were
      allowed to fuse into multinucleated myotubes for 8 days in differentiation
      medium, resulting in a population of spherical myoblasts (50%), spherical
      myotubes (35%), and elongated myotubes (15%) with an overall viability of 90%. To
      evaluate cell deformation upon construct compression half-core shaped constructs
      were compressed up to 40% strain and the resulting cell shape was assessed from
      confocal scans through the central plane of spherical cells. The ratio of cell
      diameters measured parallel and perpendicular to the axis of compression was used
      as an index of deformation (DI). The average DI of myoblasts decreased with
      strain level (0.99+/-0.03, 0.70+/-0.04, and 0.56+/-0.10 at 0%, 20%, and 40%
      strain), whereas for myotubes DI decreased up to 20% strain and then remained
      fairly constant (0.99+/-0.06, 0.55+/-0.06, 0.50+/-0.11). The discrepancy in DI
      between spherical myoblasts and myotubes at 20% strain was explained by the
      relative sensitivity of the cell membrane to buckling, which is more pronounced
      in the myotubes. Sustained compression up to 24 h at 20% strain resulted in a
      significant increase in cell damage with time as compared to unstrained controls.
      Despite differences in membrane buckling no difference in damage between
      myoblasts and spherical myotubes was observed over time, whereas the elongated
      myotubes were more susceptible to damage.

PMID- 11284671
TI  - Effects of strain level and proteoglycan depletion on preconditioning and
      viscoelastic responses of rat dorsal skin.
AB  - The mechanical response of rat dorsal skin was experimentally studied under
      cyclic uniaxial ramp stretches to various strain levels. Special emphasis was
      paid to the effects of the preconditioning protocol on the stress-strain
      relationship, and to the effects of ramp strain level and proteoglycan (PG)
      depletion, on viscoelasticity and preconditioning responses. The results show
      that preconditioning significantly reduced both the slope of the low strain
      stress-strain relationship, and the stress levels at consecutive stretch cycles.
      Following a short rest there was a significant partial recovery. Stress decay due
      to preconditioning was significant at all strain levels, and increased with
      strain. Stress relaxation was significant at all strain levels, but varied little
      with strain. Recovery following a 10 min rest was minor at all strain levels and
      varied little with strain. PG-depleted samples manifested similar response
      patterns. These results are consistent with the following notion: (1) skin
      consists of three mechanical components: elastin and proteoglycan which dominate
      the low strain response and are effected by preconditioning and (PG) depletion,
      and collagen which dominates the high strain response and is unaffected by
      preconditioning and PG depletion; (2) that the viscoelasticity of elastin and PG
      vs that of collagen are similar, so that rat dorsal skin can be regarded
      quasilinear viscoelastic.

PMID- 11284672
TI  - Structure and function of the healing medial collateral ligament in a goat model.
AB  - In this study knee joint function with a healing medial collateral ligament (MCL)
      at six weeks was examined with a robotic/universal force-moment sensor testing
      system during the application of two loading conditions: (1) 5 Nm valgus moment
      and (2) 67 N anterior load. Additionally the structural properties of the femur
      MCL-tibia complex and the mechanical properties of the MCL substance were
      determined by uniaxial tensile tests. The histological appearance of the healing
      MCL was also observed. At 30 degrees and 60 degrees of knee flexion, valgus
      rotation of the healing knee was significantly increased compared to the sham.
      The in situ force in the healing MCL was significantly lower (34+/-17 N vs 54+/
      12 N) at the same flexion angles (50+/-10 N vs 62+/-7 N). The anterior
      translation of the knee had returned to normal values at 30 degrees and 60
      degrees of knee flexion. However, no differences could be found between the
      corresponding in situ forces in the healing MCL at all flexion angles examined
      during application of an anterior load. The stiffness of the healing group
      (52.5+/-19.4 N/mm) was significantly lower than the sham group (80.3+/-26.4 N/mm)
      (p<0.04). The modulus of the healing group was also significantly decreased
      (p<0.05). The findings suggest that the tensile properties of the healing goat
      MCL and valgus knee rotation have not returned to normal at six weeks after an
      isolated MCL rupture, however, anterior translation appeared to return to sham
      levels.

PMID- 11284673
TI  - Measurement of the direct-current (Faradic) resistance of the electrode
      electrolyte interface for commonly used electrode materials.
AB  - The direct-current (Faradic) resistance is important because it is the highest
      impedance that an electrode-electrolyte interface can attain. In this study, the
      Faradic resistance (Rf) of identical pairs of 0.5 cm2 electrodes of bare and
      chlorided silver, tin and chlorided tin, nickel-silver, copper, and carbon was
      measured in contact with 0.9% saline at room temperature. It was found that for
      positive and negative current flow, the data fit the expression Rf=Rf0 e(-alpha
      i) (with a high coefficient of determination), where Rf0 is the zero-current
      Faradic resistance and alpha is a constant that describes the manner in which Rf
      decreases with increasing current (i). It was found that chlorided silver
      exhibited the lowest Rf0; removing the chloride deposit increased Rf0 by more
      than sixfold. Likewise, chloriding tin reduced Rf0 by a factor of about 2.
      Electrolytically cleaning an electrode reduced Rf0. The highest value for Rf0 was
      for carbon. This paper concludes with a summary of the data for Rf0 scaled to 1
      cm2 electrode area for the electrode materials measured in the present study and
      data from the published literature.

PMID- 11284674
TI  - Conformation and orientation of the retinyl chromophore in rhodopsin: a critical
      evaluation of recent NMR data on the basis of theoretical calculations results in
      a minimum energy structure consistent with all experimental data.
AB  - In the absence of a high-resolution diffraction structure, the orientation and
      conformation of the protonated Schiffs base retinylidinium chromophore of
      rhodopsin within the opsin matrix has been the subject of much speculation. There
      have been two recent reliable and precise NMR results that bear on this issue.
      One involves a determination of the C20-C10 and C20-C11 distances by Verdegem et
      al. [Biochemistry 38, 11316-11324 (1999)]. The other is the determination of the
      orientation of the methine C to methyl group vectors C5-C18, C9-C19, and C13-C20
      relative to the membrane normal by Grobner et al. [Nature 405 (6788), 810-813
      (2000)]. Using molecular orbital methods that include extensive configuration
      interaction, we have determined what we propose to be the minimum energy
      conformation of this chromophore. The above NMR results permit us to check this
      structure in the C10-C11=C12-C13 region and then to check the global structure
      via the relative orientation of the three C18, C19, and C20 methyl groups. This
      method provides a detailed structure and also the orientation for the retinyl
      chromophore relative to the membrane normal and argues strongly that the protein
      does not appreciably alter the chromophore geometry from its minimum energy
      configuration that is nearly planar s-trans at the 6-7 bond. Finally, the
      chromophore structure and orientation presented in the recently published X-ray
      diffraction structure is compared with our proposed structure and with the
      deuterium NMR results.

PMID- 11284675
TI  - Hierarchical folding of intestinal fatty acid binding protein.
AB  - Intestinal fatty acid binding protein (IFABP) is a member of the lipid binding
      protein family, members of which have a clam shell type of motif formed by two
      five-stranded beta-sheets. Understanding the folding mechanism of these proteins
      has been hindered by the presence of an unresolved burst phase. By initiating the
      reaction with a sub-millisecond mixer and following its progression by Trp
      fluorescence, we discovered three distinct phases in the folding reaction of the
      W6Y mutant of IFABP from which we postulate the following sequence of events. The
      first phase (k(1) > 10 000 s(-1)) involves collapse of the polypeptide chain
      around a hydrophobic core. During the second phase (k(2) approximately 1500 s(
      1)), beta-strands B-G, mostly located on the top half of the clam shell
      structure, propagate from this hydrophobic core. It is followed by the final
      phase (k(3) approximately 5 s(-1)) involving the formation of the last three beta
      strands on the bottom half of the clam shell and the establishment of the native
      hydrogen bonding network throughout the protein molecule.

PMID- 11284676
TI  - Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus
      macaque leukocytes.
AB  - Most mammalian defensins are cationic peptides of 29-42 amino acids long,
      stabilized by three disulfide bonds. However, recently Tang et al. (1999, Science
      286, 498-502) reported the isolation of a new defensin type found in the
      leukocytes of rhesus macaques. In contrast to all the other defensins found so
      far, rhesus theta defensin-1 (RTD-1) is composed of just 18 amino acids with the
      backbone cyclized through peptide bonds. Antibacterial activities of both the
      native cyclic peptide and a linear form were examined, showing that the cyclic
      form was 3-fold more active than the open chain analogue [Tang et al. (1999)
      Science 286, 498-502]. To elucidate the three-dimensional structure of RTD-1 and
      its open chain analogue, both peptides were synthesized using solid-phase peptide
      synthesis and tert-butyloxycarbonyl chemistry. The structures of both peptides in
      aqueous solution were determined from two-dimensional (1)H NMR data recorded at
      500 and 750 MHz. Structural constraints consisting of interproton distances and
      dihedral angles were used as input for simulated-annealing calculations and water
      refinement with the program CNS. RTD-1 and its open chain analogue oRTD-1 adopt
      very similar structures in water. Both comprise an extended beta-hairpin
      structure with turns at one or both ends. The turns are well defined within
      themselves and seem to be flexible with respect to the extended regions of the
      molecules. Although the two strands of the beta-sheet are connected by three
      disulfide bonds, this region displays a degree of flexibility. The structural
      similarity of RTD-1 and its open chain analogue oRTD-1, as well as their
      comparable degree of flexibility, support the theory that the additional charges
      at the termini of the open chain analogue rather than overall differences in
      structure or flexibility are the cause for oRTD-1's lower antimicrobial activity.
      In contrast to numerous other antimicrobial peptides, RTD-1 does not display any
      amphiphilic character, even though surface models of RTD-1 exhibit a certain
      clustering of positive charges. Some amide protons of RTD-1 that should be
      solvent-exposed in monomeric beta-sheet structures show low-temperature
      coefficients, suggesting the possible presence of weak intermolecular hydrogen
      bonds.

PMID- 11284677
TI  - Structure-based design of a bispecific receptor mimic that inhibits T cell
      responses to a superantigen.
AB  - Key surface proteins of pathogens and their toxins bind to the host cell
      receptors in a manner that is quite different from the way the natural ligands
      bind to the same receptors and direct normal cellular responses. Here we describe
      a novel strategy for "non-antibody-based" pathogen countermeasure by targeting
      the very same "alternative mode of host receptor binding" that the pathogen
      proteins exploit to cause infection and disease. We have chosen the
      Staphylococcus enterotoxin B (SEB) superantigen as a model pathogen protein to
      illustrate the principle and application of our strategy. SEB bypasses the normal
      route of antigen processing by binding as an intact protein to the complex formed
      by the MHC class II receptor on the antigen-presenting cell and the T cell
      receptor. This alternative mode of binding causes massive IL-2 release and T cell
      proliferation. A normally processed antigen requires all the domains of the
      receptor complex for its binding, whereas SEB requires only the alpha1 subunit
      (DRalpha) of the MHC class II receptor and the variable beta subunit (TCRVbeta)
      of the T cell receptor. This prompted us to design a bispecific chimera, DRalpha
      linker-TCRVbeta, that acts as a receptor mimic and prevents the interaction of
      SEB with its host cell receptors. We have adopted (GSTAPPA)(2) as the linker
      sequence because it supports synergistic binding of DRalpha and TCRVbeta to SEB
      and thereby makes DRalpha-(GSTAPPA)(2)-TCRVbeta as effective an SEB binder as the
      native MHC class II-T cell receptor complex. Finally, we show that DRalpha
      (GSTAPPA)(2)-TCRVbeta inhibits SEB-induced IL-2 release and T cell proliferation
      at nanomolar concentrations.

PMID- 11284678
TI  - Substrate-inhibitor interactions in the kinetics of alpha-amylase inhibition by
      ragi alpha-amylase/trypsin inhibitor (RATI) and its various N-terminal fragments.
AB  - The ragi alpha-amylase/trypsin bifunctional inhibitor (RATI) from Indian finger
      millet, Ragi (Eleucine coracana Gaertneri), represents a new class of cereal
      inhibitor family. It exhibits a completely new motif of trypsin inhibitory site
      and is not found in any known trypsin inhibitor structures. The alpha-amylase
      inhibitory site resides at the N-terminal region. These two sites are independent
      of each other and the inhibitor forms a ternary (1:1:1) complex with trypsin and
      alpha-amylase. The trypsin inhibition follows a simple competitive inhibition
      obeying the canonical serine protease inhibitor mechanism. However, the alpha
      amylase inhibition kinetics is a complex one if larger (> or =7 glucose units)
      substrate is used. While a complete inhibition of trypsin activity can be
      achieved, the inhibition of amylase is not complete even at very high molar
      concentration. We have isolated the N-terminal fragment (10 amino acids long) by
      CNBr hydrolysis of RATI. This fragment shows a simple competitive inhibition of
      alpha-amylase activity. We have also synthesized various peptides homologous to
      the N-terminal sequence of RATI. These peptides also show a normal competitive
      inhibition of alpha-amylase with varying potencies. It has also been shown that
      RATI binds to the larger substrates of alpha-amylase. In light of these
      observations, we have reexamined the binding of proteinaceous inhibitors to alpha
      amylase and its implications on the mechanism and kinetics of inhibition.

PMID- 11284679
TI  - Structural basis for a change in substrate specificity: crystal structure of
      S113E isocitrate dehydrogenase in a complex with isopropylmalate, Mg2+, and NADP.
AB  - Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of
      isocitrate and has negligible activity toward other (R)-malate-type substrates.
      The S113E mutant of IDH significantly improves its ability to utilize
      isopropylmalate as a substrate and switches the substrate specificity
      (k(cat)/K(M)) from isocitrate to isopropylmalate. To understand the structural
      basis for this switch in substrate specificity, we have determined the crystal
      structure of IDH S113E in a complex with isopropylmalate, NADP, and Mg(2+) to 2.0
      A resolution. On the basis of a comparison with previously determined structures,
      we identify distinct changes caused by the amino acid substitution and by the
      binding of substrates. The S113E complex exhibits alterations in global and
      active site conformations compared with other IDH structures that include loop
      and helix conformational changes near the active site. In addition, the angle of
      the hinge that relates the two domains was altered in this structure, which
      suggests that the S113E substitution and the binding of substrates act together
      to promote catalysis of isopropylmalate. Ligand binding results in reorientation
      of the active site helix that contains residues 113 through 116. E113 exhibits
      new interactions, including van der Waals contacts with the isopropyl group of
      isopropylmalate and a hydrogen bond with N115, which in turn forms a hydrogen
      bond with NADP. In addition, the loop and helix regions that bind NADP are
      altered, as is the loop that connects the NADP binding region to the active site
      helix, changing the relationship between substrates and enzyme. In combination,
      these interactions appear to provide the basis for the switch in substrate
      specificity.

PMID- 11284680
TI  - Interligand Overhauser effects in type II dihydrofolate reductase.
AB  - R67 dihydrofolate reductase (DHFR) is a type II DHFR produced by bacteria as a
      resistance mechanism to the increased clinical use of the antibacterial drug
      trimethoprim. Type II DHFRs are not homologous in either sequence or structure
      with chromosomal DHFRs. The type II enzymes contain four identical subunits which
      form a homotetramer containing a single active site pore accessible from either
      end. Although the crystal structure of the complex of R67 DHFR with folate has
      been reported [Narayana et al. (1995) Nat. Struct. Biol. 2, 1018], the nature of
      the ternary complex which must form with substrate and cofactor is unclear. We
      have performed transferred NOE and interligand NOE (ILOE) studies to analyze the
      ternary complexes formed from NADP(+) and folate in order to probe the structure
      of the ternary complex. Consistent with previous studies of the binary complex
      formed from another type II DHFR, the ribonicotinamide bond of NADP(+) was found
      to adopt a syn conformation, while the adenosine moiety adopts an anti
      conformation. Large ILOE peaks connecting NADP(+) H4 and H5 with folate H9
      protons are observed, while the absence of a large ILOE connecting NADP(+) H4 and
      H5 with folate H7 indicates that the relative orientation of the two ligands
      differs significantly from the orientation in the chromosomal enzyme. To obtain
      more detailed insight, we prepared and studied the folate analogue 2-deamino-2
      methyl-5,8-dideazafolate (DMDDF) which contains additional protons in order to
      provide additional NOEs. For this analogue, the exchange characteristics of the
      corresponding ternary complex were considerably poorer, and it was necessary to
      utilize higher enzyme concentrations and higher temperature in order to obtain
      ILOE information. The results support a structure in which the NADP(+) and
      folate/DMDDF molecules extend in opposite directions parallel to the long axis of
      the pore, with the nicotinamide and pterin ring systems approximately stacked at
      the center. Such a structure leads to a ternary complex which is in many respects
      similar to the gas-phase theoretical calculations of the dihydrofolate-NADPH
      transition state by Andres et al. [(1996) Bioorg. Chem. 24, 10-18]. Analogous NMR
      studies performed on folate, DMDDF, and R67 DHFR indicate formation of a ternary
      complex in which two symmetry-related binding sites are occupied by folate and
      DMDDF.

PMID- 11284681
TI  - X-ray structure analyses of photosynthetic reaction center variants from
      Rhodobacter sphaeroides: structural changes induced by point mutations at
      position L209 modulate electron and proton transfer.
AB  - The structures of the reaction center variants Pro L209 --> Tyr, Pro L209 -->
      Phe, and Pro L209 --> Glu from the photosynthetic purple bacterium Rhodobacter
      sphaeroides have been determined by X-ray crystallography to 2.6-2.8 A
      resolution. These variants were constructed to interrupt a chain of tightly bound
      water molecules that was assumed to facilitate proton transfer from the cytoplasm
      to the secondary quinone Q(B) [Baciou, L., and Michel, H. (1995) Biochemistry 34,
      7967-7972]. However, the amino acid exchanges Pro L209 --> Tyr and Pro L209 -->
      Phe do not interrupt the water chain. Both aromatic side chains are oriented away
      from this water chain and interact with three surrounding polar side chains (Asp
      L213, Thr L226, and Glu H173) which are displaced by up to 2.6 A. The
      conformational changes induced by the bulky aromatic rings of Tyr L209 and Phe
      L209 lead to unexpected displacements of Q(B) compared to the wild-type protein.
      In the structure of the Pro L209 --> Tyr variant, Q(B) is shifted by
      approximately 4 A and is now located at a position similar to that reported for
      the wild-type reaction center after illumination [Stowell, M. H. B., et al.
      (1997) Science 276, 812-816]. In the Pro L209 --> Phe variant, the electron
      density map reveals an intermediate Q(B) position between the binding sites of
      the wild-type protein in the dark and the Pro L209 --> Tyr protein. In the Pro
      L209 --> Glu reaction center, the carboxylic side chain of Glu L209 is located
      within the water chain, and the binding site of Q(B) remains unchanged compared
      to the wild-type structure.

PMID- 11284682
TI  - Structural basis for the functional switch of the E. coli Ada protein.
AB  - The Escherichia coli protein Ada specifically repairs the S(p) diastereomer of
      DNA methyl phosphotriesters in DNA by direct and irreversible transfer of the
      methyl group to its own Cys 69 which is part of a zinc-thiolate center. The
      methyl transfer converts Ada into a transcriptional activator that binds sequence
      specifically to promoter regions of its own gene and other methylation resistance
      genes. Ada thus acts as a chemosensor to activate repair mechanisms in situations
      of methylation damage. Here we present a highly refined solution structure of the
      10 kDa N-terminal domain, N-Ada10, which reveals structural details of the
      nonspecific DNA interaction of N-Ada10 during the repair process and provides a
      basis for understanding the mechanism of the conformational switch triggered by
      methyl transfer. To further elucidate this, EXAFS (extended X-ray absorption fine
      structure) and XANES (X-ray absorption near-edge structure) data were acquired,
      which confirmed that the zinc-thiolate center is maintained when N-Ada is
      methylated. Thus, ligand exchange is not the mechanism that enhances sequence
      specific DNA binding and transcriptional activation upon methylation of N-Ada.
      The mechanism of the switch was further elucidated by recording NOESY spectra of
      specifically labeled methylated-Ada/DNA complexes, which showed that the
      transferred methyl group makes many contacts within N-Ada but none with the DNA.
      This implies that methylation of N-Ada induces a structural change, which
      enhances the promoter affinity of a remodeled surface region that does not
      include the transferred methyl group.

PMID- 11284683
TI  - Selective binding by the RNA binding domain of PKR revealed by affinity cleavage.
AB  - The RNA-dependent protein kinase (PKR) is regulated by the binding of double
      stranded RNA (dsRNA) or single-stranded RNAs with extensive duplex secondary
      structure. PKR has an RNA binding domain (RBD) composed of two copies of the
      dsRNA binding motif (dsRBM). The dsRBM is an alpha-beta-beta-beta-alpha structure
      present in a number of proteins that bind RNA, and the selectivity demonstrated
      by these proteins is currently not well understood. We have used affinity
      cleavage to study the binding of PKR's RBD to RNA. In this study, we site
      specifically modified the first dsRBM of PKR's RBD at two different amino acid
      positions with the hydroxyl radical generator EDTA.Fe. Cleavage by these proteins
      of a synthetic stem-loop ligand of PKR indicates that PKR's dsRBMI binds the RNA
      in a preferred orientation, placing the loop between strands beta1 and beta2 near
      the single-stranded RNA loop. Additional cleavage experiments demonstrated that
      defects in the RNA stem, such as an A bulge and two GA mismatches, do not dictate
      dsRBMI's binding orientation preference. Cleavage of VA(I) RNA, an adenoviral RNA
      inhibitor of PKR, indicates that dsRBMI is bound near the loop of the apical stem
      of this RNA in the same orientation as observed with the synthetic stem-loop RNA
      ligands. This work, along with an NMR study of the binding of a dsRBM derived
      from the Drosophila protein Staufen, indicates that dsRBMs can bind stem-loop
      RNAs in distinct ways. In addition, the successful application of the affinity
      cleavage technique to localizing dsRBMI of PKR on stem-loop RNAs and defining its
      orientation suggests this approach could be applied to dsRBMs found in other
      proteins.

PMID- 11284684
TI  - Dynamics of the proton transfer reaction on the cytoplasmic surface of
      bacteriorhodopsin.
AB  - The cytoplasmic surface of bacteriorhodopsin is characterized by a group of
      carboxylates that function as a proton attractive domain [Checover, S., Nachliel,
      E., Dencher, N. A., and Gutman, M. (1997) Biochemistry 36, 13919-13928]. To
      identify these carboxylates, we selectively mutated them into cysteine residues
      and monitored the effects of the dynamics of proton transfer between the bulk and
      the surface of the protein. The measurements were carried out without attachment
      of a pH-sensor to the cysteine residue, thus avoiding any structural perturbation
      and change in the surface charge caused by the attachment of a reporter group,
      and the protein was in its BR state. The purple membranes were suspended in an
      unbuffered solution of pyranine (8-hydroxypyrene-1,3,6-trisulfonate) and exposed
      to a train of 1000 laser pulses (2.1 mJ/pulse, lambda = 355 nm, at 10 Hz). The
      excitation of the dye ejected the hydroxyl's proton, and a few nanoseconds later,
      a pair of free protons and ground-state pyranine anion was formed. The
      experimental observation was the dynamics of the relaxation of the system to the
      prepulse state. The observed signals were reconstructed by a numeric method that
      replicates the chemical reactions proceeding in the perturbed space. The detailed
      reconstruction of the measured signal assigned the various proton-binding sites
      with rate constants for proton binding and proton exchange and the pK values.
      Comparison of the results obtained by the various mutants indicates that the
      dominant proton-binding cluster of the wild-type protein consists of D104, E161,
      and E234. The replacement of D104 or E161 with cysteine lowered the proton
      binding capacity of the cluster to approximately 60% of that of the native
      protein. The replacement of E234 with cysteine disrupted the structure of the
      cluster, causing the two remaining carboxylates to function as isolated residues
      that do not interact with each other. The possibility of proton transfer between
      monomers is discussed.

PMID- 11284685
TI  - Solution structure of the transcriptional activation domain of the bacteriophage
      T4 protein, MotA.
AB  - Bacteriophage T4 encodes a transcription factor, MotA, that binds to the -30
      region of middle-mode promoters and activates transcription by host RNA
      polymerase. The crystal structure of the N-terminal domain of MotA (MotNF)
      revealed a six-helix domain in which the two C-terminal alpha-helices mediate the
      formation of a dimer via a coiled-coil motif and hydrophobic interactions. This
      structure suggested that full-length MotA binds DNA as a dimer, but subsequent
      biochemical results have shown that a monomeric form of MotA binds DNA. In this
      study, gel filtration chromatography, dynamic light scattering, and NMR-based
      diffusion measurements show conclusively that MotNF is a monomer, and not a
      dimer, in solution. In addition, we have determined the monomeric solution
      structure of MotNF using NMR spectroscopy, and have compared this with the dimer
      structure observed in crystals. The core of the protein assumes the same helical
      conformation in solution and in crystals, but important differences are observed
      at the extreme C-terminus. In solution, helix alpha5 is followed by five
      disordered residues that probably link the N-terminal and C-terminal domains of
      MotA. In crystals, helix alpha5 forms the dimer interface and is followed by a
      short sixth helix that further stabilizes the dimer configuration. The solution
      structure of MotNF supports the conclusion that MotA functions as a monomer, and
      suggests that the existence of the sixth helix in crystals is a consequence of
      crystal packing. Our work highlights the importance of investigating protein
      structures in both crystals and solution to fully understand biomolecular
      structure and to accurately deduce relationships between structure and function.

PMID- 11284686
TI  - Role of the flexible loop of hypoxanthine-guanine-xanthine
      phosphoribosyltransferase from Tritrichomonas foetus in enzyme catalysis.
AB  - The hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase), a type I
      PRTase, from Tritrichomonas foetus, is a potential target for antitritrichomonal
      chemotherapy. Structural data on all the type I PRTases reveal a highly flexible,
      11-14-amino acid loop, presumably covering the active site. With the exception of
      a highly conserved Ser-Tyr dipeptide, the other amino acids constituting the loop
      vary widely among different PRTases. The roles of the conserved Ser73 and Tyr74
      residues in the loop and the dynamics of the loop in T. foetus HGXPRTase were
      investigated using site-directed mutants, stop-flow kinetics, chemical
      modification, and two-dimensional (1)H-(15)N heteronuclear NMR relaxation
      experiments. S73A, Y74F, and Y74E mutants of HGXPRTase exhibited a 5-7-fold
      increase in K(m) for guanine and a 3-5-fold increase in K(m) for PRPP compared to
      that of the wild type, reflecting the decreased affinity of binding for the two
      substrates. The k(cat)'s for these mutant-catalyzed reactions, however, do not
      change appreciably from that of the wild-type enzyme. Stopped-flow fluorescence
      with a Y74W mutant showed no apparent quenching by adding either PRPP or GMP
      alone. When both PRPP and guanine were added together, however, the fluorescence
      was rapidly quenched, followed by a slow recovery as the enzyme-catalyzed
      reaction progressed, suggesting movement of the loop during catalysis. In the
      presence of 9-deazaguanine and PRPP, the rapidly quenched fluorescence was not
      recovered, suggesting a closed loop form. The accessibility of Trp74 in the
      flexible loop of the mutant enzyme was also analyzed using N-bromosuccinimide
      (NBS), which reacts specifically with the tryptophan residue. NBS reacted with
      the only tryptophan in the Y74W mutant enzyme and rendered the enzyme inactive.
      GMP or PRPP alone failed to protect the enzyme from NBS inactivation. However,
      the presence of both 9-deazaguanine and PPRP protected the enzyme, allowing it to
      retain up to 70% of its activity. An S75H mutant, labeled with [(15)N]histidine,
      was used in the (1)H-(15)N NMR study. Spectra obtained in the presence of enzyme
      substrates indicated an apparent stabilization of the loop only in the presence
      of 9-deazaguanine and PRPP. These experimental results thus clearly demonstrated
      stabilization of the flexible loop upon binding of both PRPP and guanine and
      suggested its involvement in enzyme catalysis.

PMID- 11284687
TI  - Analysis of MDR1 P-glycoprotein conformational changes in permeabilized cells
      using differential immunoreactivity.
AB  - The reactivity of the ATP-dependent multidrug transporter P-glycoprotein (Pgp)
      with the conformation-sensitive monoclonal antibody UIC2 is increased in the
      presence of Pgp transport substrates, ATP-depleting agents, or mutations that
      reduce the level of nucleotide binding by Pgp. We have investigated the effects
      of nucleotides and vinblastine, a Pgp transport substrate, on the UIC2 reactivity
      of Pgp in cells permeabilized by Staphylococcus aureus alpha-toxin. ATP, ADP, and
      nonhydrolyzable ATP analogues decreased the UIC2 reactivity; this effect was
      potentiated by vanadate, a nucleotide-trapping agent. The Hill number for the
      nucleotide-induced conformational transition was 2 for ATP and ADP but 1 for
      nonhydrolyzable ATP analogues. The Hill numbers for ATP and ADP were decreased to
      1 by mutations in one of the two nucleotide binding sites of Pgp, whereas
      mutation of both sites greatly diminished the overall effect of nucleotides.
      Vinblastine reversed the decrease in the UIC2 reactivity brought about by all the
      nucleotides, including nonhydrolyzable analogues; this effect of vinblastine was
      blocked by vanadate. These data indicate that UIC2-detectable conformational
      changes of Pgp are driven by binding and debinding of nucleotides, that
      nucleotide hydrolysis affects the Hill number for its Pgp interactions, and that
      Pgp transport substrates promote nucleotide dissociation from Pgp. These findings
      are consistent with a conventional E1/E2 model that explains conformational
      transitions of a transporter protein through a series of linked equilibria.

PMID- 11284688
TI  - P-glycoprotein-mediated colchicine resistance in different cell lines correlates
      with the effects of colchicine on P-glycoprotein conformation.
AB  - The multidrug transporter P-glycoprotein (Pgp) is an ATPase efflux pump for
      multiple cytotoxic agents, including vinblastine and colchicine. We have found
      that resistance to vinblastine but not to colchicine in cell lines derived from
      different types of tissues and expressing the wild-type human Pgp correlates with
      the Pgp density. Vinblastine induces a conformational change in Pgp, evidenced by
      increased reactivity with a conformation-sensitive monoclonal antibody UIC2, in
      all the tested cell lines. In contrast, colchicine increases the UIC2 reactivity
      in only some of the cell lines. In those lines where colchicine alone did not
      affect UIC2 reactivity, this drug was, however, able to reverse the vinblastine
      induced increase in UIC2 reactivity. The magnitude of the increase in UIC2
      reactivity in the presence of saturating concentrations of colchicine correlates
      with the relative ability of Pgp to confer colchicine resistance in different
      cell lines, suggesting the existence of some cell-specific factors that have a
      coordinate effect on the ability of colchicine to induce conformational
      transitions and to be transported by Pgp. Colchicine, like vinblastine, reverses
      the decrease in UIC2 reactivity produced by nonhydrolyzable nucleotides, but
      unlike vinblastine, it does not reverse the effect of ATP at a high
      concentration. Colchicine, however, decreases the Hill number for the effect of
      ATP on the UIC2 reactivity from 2 to 1. Colchicine increases the UIC2 reactivity
      and reverses the effect of ATP in ATPase-deficient Pgp mutants, but not in the
      wild-type Pgp expressed in the same cellular background, suggesting that ATP
      hydrolysis counteracts the effects of colchicine on the Pgp conformation.

PMID- 11284689
TI  - Coordinate changes in drug resistance and drug-induced conformational transitions
      in altered-function mutants of the multidrug transporter P-glycoprotein.
AB  - The MDR1 P-glycoprotein (Pgp), responsible for a clinically important form of
      multidrug resistance in cancer, is an ATPase efflux pump for multiple lipophilic
      drugs. The G185V mutation near transmembrane domain 3 of human Pgp increases its
      relative ability to transport several drugs, including etoposide, but decreases
      the transport of other substrates. MDR1 cDNA with the G185V substitution was used
      in a function-based selection to identify mutations that would further increase
      Pgp-mediated resistance to etoposide. This selection yielded the I186N
      substitution, adjacent to G185V. Pgps with G185V, I186N, or both mutations were
      compared to the wild-type Pgp for their ability to confer resistance to different
      drugs in NIH 3T3 cells. In contrast to the differential effects of G185V, I186N
      mutation increased resistance to all the tested drugs and augmented the effect of
      G185V on etoposide resistance. The effects of the mutations on conformational
      transitions of Pgp induced by different drugs were investigated using a
      conformation-sensitive antibody UIC2. Ligand-binding analysis of the drug-induced
      increase in UIC2 reactivity was used to determine the K(m) value that reflects
      the apparent affinity of drugs for Pgp, and the Hill number reflecting the
      apparent number of drug-binding sites. Both mutations altered the magnitude of
      drug-induced increases in UIC2 immunoreactivity, the K(m) values, and the Hill
      numbers for individual drugs. Mutation-induced changes in the magnitude of UIC2
      reactivity shift did not correlate with the effects of the mutations on
      resistance to the corresponding drugs. In contrast, an increase or a decrease in
      drug resistance relative to that of the wild type was accompanied by a
      corresponding increase or decrease in the K(m) or in both the K(m) and the Hill
      number. These results suggest that mutations that alter the ability of Pgp to
      transport individual drugs change the apparent affinity and the apparent number
      of drug-binding sites in Pgp.

PMID- 11284690
TI  - Influence of lipid composition on physical properties and peg-mediated fusion of
      curved and uncurved model membrane vesicles: "nature's own" fusogenic lipid
      bilayer.
AB  - Poly(ethylene glycol) (PEG)-mediated fusion of phosphatidylcholine model
      membranes has been shown to mimic the protein-mediated biomembrane process [Lee,
      J., and Lentz, B. R. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 9274-9279]. Unlike
      the simple model membranes used in this earlier study, the lipid composition of
      fusogenic biomembranes is quite complex. The purpose of this paper was to examine
      PEG-mediated fusion of highly curved (SUV) and largely uncurved (LUV) membrane
      vesicles composed of different lipids in order to identify lipid compositions
      that produce highly fusogenic membranes. Starting with liposomes composed of five
      lipids with different physical properties, dioleoylphosphatidylcholine (DOPC),
      dioleoylphosphatidylethanolamine (DOPE), dioleoylphosphatidylserine (DOPS),
      bovine brain sphingomyelin (SM), and cholesterol (CH), we systematically varied
      the composition and tested for the extent of PEG-mediated fusion after 5 min of
      treatment. We found that a vesicle system composed of four lipids,
      DOPC/DOPE/SM/CH, fused optimally at a 35/30/15/20 molar ratio. Each lipid seemed
      to play a part in optimizing the membrane for fusion. PE disrupted outer leaflet
      packing as demonstrated with TMA-DPH lifetime, C(6)-NBD-PC partitioning, and DPH
      anisotropy measurements, and thus significantly enhanced fusion and rupture,
      without significantly altering interbilayer approach (X-ray diffraction). An
      optimal ratio of PC/PE (35/30) produced a balance between fusion and rupture. CH
      and SM, when present at an optimal ratio of 3/4 in vesicles containing the
      optimal PC/PE ratio, reduced rupture without significantly reducing fusion. This
      optimal CH/SM ratio also enhanced outer leaflet packing, suggesting that fusion
      is dependent not only on outer leaflet packing but also on the properties of the
      inner leaflet. Addition of CH without SM enhanced rupture relative to fusion,
      while SM alone reduced both rupture and fusion. The optimal lipid composition is
      very close to the natural synaptic vesicle composition, suggesting that the
      synaptic vesicle composition is optimized with respect to fusogenicity.

PMID- 11284691
TI  - Ability of the Tat basic domain and VP22 to mediate cell binding, but not
      membrane translocation of the diphtheria toxin A-fragment.
AB  - A number of proteins are able to enter cells from the extracellular environment,
      including protein toxins, growth factors, viral proteins, homeoproteins, and
      others. Many such translocating proteins, or parts of them, appear to be able to
      carry with them cargo into the cell, and a basic sequence from the HIV-1 Tat
      protein has been reported to provide intracellular delivery of several fused
      proteins. For evaluating the efficiency of translocation to the cytosol, this TAT
      peptide was fused to the diphtheria toxin A-fragment (dtA), an extremely potent
      inhibitor of protein synthesis which normally is delivered efficiently to the
      cytosol by the toxin B-fragment. The fusion of the TAT-peptide to dtA converted
      the protein to a heparin-binding protein that bound avidly to the cell surface.
      However, no cytotoxicity of this protein was detected, indicating that the TAT
      peptide is unable to efficiently deliver enzymatically active dtA to the cytosol.
      Interestingly, the fused TAT-peptide potentiated the binding and cytotoxic effect
      of the corresponding holotoxin. We made a fusion protein between VP22, another
      membrane-permeant protein, and dtA, and also in this case we detected association
      with cells in the absence of a cytotoxic effect. The data indicate that transport
      of dtA into the cell by the TAT-peptide and VP22 is inefficient.

PMID- 11284692
TI  - Enhanced potency of human Sonic hedgehog by hydrophobic modification.
AB  - Post-translational modifications of the developmental signaling protein Sonic
      hedgehog (Shh) by a long-chain fatty acid at the N-terminus and cholesterol at
      the C-terminus greatly activate the protein in a cell-based signaling assay. To
      investigate the structural determinants of this activation phenomenon,
      hydrophobic and hydrophilic moieties have been introduced by chemical and
      mutagenic methods to the soluble N-terminal signaling domain of Shh and tested in
      both in vitro and in vivo assays. A wide variety of hydrophobic modifications
      increased the potency of Shh when added at the N-terminus of the protein, ranging
      from long-chain fatty acids to hydrophobic amino acids, with EC(50) values from
      99 nM for the unmodified protein to 0.6 nM for the myristoylated form. The N
      myristoylated Shh was as active as the natural form having both N- and C-terminal
      modifications. The degree of activation appears to correlate with the
      hydrophobicity of the modification rather than any specific chemical feature of
      the adduct; moreover, substitution with hydrophilic moieties decreased activity.
      Hydrophobic modifications at the C-terminus of Shh resulted in only a 2-3-fold
      increase in activity, and no activation was found with hydrophobic modification
      at other surface positions. The N-terminal modifications did not appear to alter
      the binding affinity of the Shh protein for the transfected receptor protein,
      Patched, and had no apparent effect on structure as measured by circular
      dichroism, thermal denaturation, and size determination. Activation of Desert Hh
      through modification of its N-terminus was also observed, suggesting that this is
      a common feature of Hh proteins.

PMID- 11284693
TI  - Posttranslational modifications of microfibril associated glycoprotein-1 (MAGP
      1).
AB  - Microfibril-associated glycoprotein-1 (MAGP-1) is a small molecular weight
      protein associated with extracellular matrix microfibrils. Biochemical studies
      have shown that MAGP-1 undergoes several posttranslational modifications that may
      influence its associations with other microfibrillar components. To identify the
      sites in the molecule where posttranslational modifications occur, we expressed
      MAGP-1 constructs containing various point mutations as well as front and back
      half truncations in CHO cells. Characterization of transiently expressed protein
      showed that MAGP-1 undergoes O-linked glycosylation and tyrosine sulfation at
      sites in its amino-terminal half. This region of the protein also served as a
      major amine acceptor site for transglutaminase and mediated self-assembly into
      high molecular weight multimers through a glutamine-rich sequence. Fine mapping
      of the modification sites through mutational analysis demonstrated that Gln20 is
      a major amine acceptor site for the transglutaminase reaction and confirmed that
      a canonical tyrosine sulfation consensus sequence is the site of MAGP-1
      sulfation. Our results also show that O-glycosylation occurs at more than one
      site in the molecule.

PMID- 11284694
TI  - Insight into the chemistry of flavin reduction and oxidation in Escherichia coli
      dihydroorotate dehydrogenase obtained by rapid reaction studies.
AB  - Dihydroorotate dehydrogenase (DHOD) oxidizes dihydroorotate (DHO) to orotate in
      the only redox reaction of pyrimidine biosynthesis. The enzyme from Escherichia
      coli is a membrane-bound FMN-containing enzyme that is thought to use ubiquinone
      as the oxidizing substrate. The chemistry of the reduction of the flavin in DHOD
      from E. coli by the substrate dihydroorotate (DHO) was studied at 4 degrees C in
      anaerobic stopped-flow experiments conducted over a broad range of pH values. A
      Michaelis complex that was characterized by a approximately 20 nm red-shift of
      the oxidized flavin absorbance formed within the dead-time of the stopped-flow
      instrument ( approximately 1 ms) upon mixing with DHO. The flavin of the
      intermediate was reduced by DHO, forming a reduced flavin-orotate charge-transfer
      complex. The rate constant for the flavin reduction reaction increased with pH,
      from a value of 1 s(-1) at pH 6.5 to approximately 360 s(-1) at pH values greater
      than an observed pK(a) of 9.5 which was ascribed to Ser175, the active-site base.
      At all pH values, the reduced flavin-orotate charge-transfer complex dissociated
      too slowly to be catalytically relevant. Therefore, the oxidizing quinone
      substrate must bind to the reduced enzyme-orotate complex at a site distinct from
      the substrate binding site, in agreement with steady-state kinetic studies
      [Bjornberg, O., Gruner, A.-C., Roepstorff, P., and Jensen, K. F. (1999)
      Biochemistry 38, 2899-2908]. Menadione was used as a model quinone substrate to
      oxidize dithionite-reduced DHOD. The reduced enzyme-orotate complex reacted
      rapidly with menadione (180 s(-1)), demonstrating that the reduced enzyme-orotate
      complex is a catalytically competent intermediate.

PMID- 11284695
TI  - Inhibition studies of soybean and human 15-lipoxygenases with long-chain alkenyl
      sulfate substrates.
AB  - Lipoxygenases are currently potential targets for therapies against asthma,
      artherosceloris, and cancer. Recently, inhibition studies on both soybean (SLO)
      and human lipoxygenase (15-HLO) revealed the presence of an allosteric site that
      binds both substrate, linoleic acid, and inhibitors; oleic acid (OA) and oleyl
      sulfate (OS). OS (K(D) approximately 0.6 microM) is a approximately 30-fold more
      potent inhibitor than OA (K(D) approximately 20 microM) due to the increased
      ionic strength of the sulfate moiety. To further investigate the role of the
      sulfate moiety on lipoxygenase function, SLO and 15-HLO were assayed against
      several fatty sulfate substrates (linoleyl sulfate (LS), cis-11,14-eicosadienoyl
      sulfate, and arachidonyl sulfate). The results demonstrate that SLO catalyzes all
      three fatty sulfate substrates and is not inhibited, indicating a binding
      selectivity of LS for the catalytic site and OS for the allosteric site. The 15
      HLO, however, manifests parabolic inhibition kinetics with increasing substrate
      concentration, and it is irreversibly inhibited by these fatty sulfate substrates
      at high concentrations. The inhibition can be stopped, however, by the addition
      of detergent to the fatty sulfate mixture prior to the addition of 15-HLO. These
      results, combined with the modeling of the kinetic data, indicate that the
      inhibition of 15-HLO is due to a substrate aggregate. These substrate aggregates,
      however, do not inhibit SLO and could present a novel mode of inhibition for 15
      HLO.

PMID- 11284696
TI  - Transition state analysis and requirement of Asp-262 general acid/base catalyst
      for full activation of dual-specificity phosphatase MKP3 by extracellular
      regulated kinase.
AB  - Dual-specificity phosphatase MKP3 down-regulates mitogenic signaling through
      dephosphorylation of extracellular regulated kinase (ERK). Unlike a simple
      substrate-enzyme interaction, the noncatalytic, amino-terminal domain of MKP3 can
      bind efficiently to ERK, leading to activation of the phosphatase catalytic
      domain by as much as 100-fold toward exogenous substrates. It has been suggested
      that ERK activates MKP3 through the stabilization of the active phosphatase
      conformation, enabling general acid catalysis. Here, we investigated whether Asp
      262 of MKP3 is the bona fide general acid and evaluated its contribution to the
      catalytic steps activated by ERK. Using site-directed mutagenesis, pH rate and
      Bronsted analyses, kinetic isotope effects, and steady-state and rapid reaction
      kinetics, Asp-262 was identified as the authentic general acid catalyst, donating
      a proton to the leaving group oxygen during P-O bond cleavage. Kinetic isotope
      effects [(18)(V/K)(bridge), (18)(V/K)(nonbridge), and (15)(V/K)] were evaluated
      for the effect of ERK and of the D262N mutation on the transition state of the
      phosphoryl transfer reaction. The patterns of the three isotope effects for the
      reaction with native MKP3 in the presence of ERK are indicative of a reaction
      where the leaving group is protonated in the transition state, whereas in the
      D262N mutant, the leaving group departs as the anion. Even without general acid
      catalysis, the D262N mutant reaction is activated by ERK through increased
      phosphate affinity ( approximately 8-fold) and the partial stabilization of the
      transition state for phospho-enzyme intermediate formation ( approximately 4
      fold). Based on these analyses, we estimate that dephosphorylation of
      phosphorylated ERK by the D262N mutant is >1000-fold lower than by native,
      activated MKP3. Also, the kinetic results suggest that Asp-262 functions as a
      general base during thiol-phosphate intermediate hydrolysis.

PMID- 11284697
TI  - Characterization of a 95 kDa high affinity human high density lipoprotein-binding
      protein.
AB  - A new human 95 kDa high density lipoprotein (HDL)-binding protein (HBP)
      corresponding to a high affinity HDL-binding site with K(d) = 1.67 microg/mL and
      a capacity of 13.4 ng/mg was identified in human fetal hepatocytes. The HDL
      binding with the 95 kDa HBP plateaus at 2.5-5 microg/mL under reducing and
      nonreducing conditions. The association of HDL(3) with the 95 kDa HBP plateaued
      in 15-30 min while dissociation was complete in 30 min. HDL(3), apoA-I, and apoA
      II were recognized by the 95 kDa HBP while low density lipoproteins (LDL) and
      tetranitromethane-modified HDL were not. The 95 kDa HBP predominantly resides on
      the surface of cells since trypsin treatment of HepG2 cells eliminated nearly 70%
      of HDL binding. All studied human cells and cell lines (HepG2, Caco-2, HeLa,
      fibroblasts, SKOV-3, PA-I) demonstrated the presence of the 95 kDa protein. Both
      RT-PCR and Western blotting for HB-2/ALCAM were negative in human fetal
      hepatocytes while Gp96/GRP94 was clearly differentiated from the 95 kDa HBP by
      two-dimensional electrophoretic mobility. Moreover, deglycosylation of HepG2
      membrane preparations did not affect either HDL binding to the 95 kDa HBP or its
      size, while in contrast it affected the molecular weights of HB-2/ALCAM and SR
      BI/CLA-1. We conclude that the 95 kDa HBP is a new HDL receptor candidate widely
      expressed in human cells and cell lines.

PMID- 11284698
TI  - Substrate specificity characterization of recombinant metallo oligo-peptidases
      thimet oligopeptidase and neurolysin.
AB  - We report a systematic and detailed analysis of recombinant neurolysin (EC
      3.4.24.16) specificity in parallel with thimet oligopeptidase (TOP, EC 3.4.24.15)
      using Bk sequence and its C- and N-terminal extensions as in human kininogen as
      motif for synthesis of internally quenched fluorescent substrates. The influence
      of the substrate size was investigated, and the longest peptide susceptible to
      TOP and neurolysin contains 17 amino acids. The specificities of both
      oligopeptidases to substrate sites P(4) to P(3)' were also characterized in great
      detail using seven series of peptides based on Abz-GFSPFRQ-EDDnp taken as
      reference substrate. Most of the peptides were hydrolyzed at the bond
      corresponding to P(4)-F(5) in the reference substrate and some of them were
      hydrolyzed at this bond or at F(2)-S(3) bond. No restricted specificity was found
      for P(1)' as found in thermolysin as well for P(1) substrate position, however
      the modifications at this position (P(1)) showed to have large influence on the
      catalytic constant and the best substrates for TOP contained at P(1), Phe, Ala,
      or Arg and for neurolysin Asn or Arg. Some amino acid residues have large
      influence on the K(m) constants independently of its position. On the basis of
      these results, we are hypothesizing that some amino acids of the substrates can
      bind to different sub-sites of the enzyme fitting P-F or F-S bond, which requires
      rapid interchange for the different forms of interaction and convenient
      conformations of the substrate in order to expose and fit the cleavage bonds in
      correct position for an efficient hydrolysis. Finally, this plasticity of
      interaction with the substrates can be an essential property for a class of
      cytosolic oligopeptidases that are candidates to participate in the selection of
      the peptides to be presented by the MHC class I.

PMID- 11284699
TI  - Spectroscopic properties of the metalloregulatory Cd(II) and Pb(II) sites of S.
      aureus pI258 CadC.
AB  - Staphylococcus aureus pI258 CadC is an extrachromosomally encoded
      metalloregulatory repressor protein from the ArsR superfamily which negatively
      regulates the expression of the cad operon in a metal-dependent fashion. The
      metalloregulatory hypothesis holds that direct binding of thiophilic divalent
      cations including Cd(II), Pb(II), and Zn(II) by CadC allosterically regulates the
      DNA binding activity of CadC to the cad operator/promoter (O/P). This report
      presents a detailed characterization of the metal binding and DNA binding
      properties of wild-type CadC. The results of analytical ultracentrifugation
      experiments suggest that both apo- and Cd(1)-CadC are stable or weakly
      dissociable homodimers characterized by a K(dimer) = 3.0 x 10(6) M(-1) (pH 7.0,
      0.20 M NaCl, 25.0 degrees C) with little detectable effect of Cd(II) on the
      dimerization equilibrium. As determined by optical spectroscopy, the
      stoichiometry of Cd(II) and Pb(II) binding is approximately 0.7-0.8 mol/mol of
      wild-type CadC monomer. Chelator (EDTA) competition binding isotherms reveal that
      Cd(II) binds very tightly, with K(Cd) = 4.3 (+/-1.8) x 10(12) M(-1). The results
      of UV-Vis and X-ray absorption spectroscopy of the Cd(1) complex are consistent
      with a tetrathiolate (S(4)) complex formed by four cysteine ligands. The (113)Cd
      NMR spectrum reveals a single resonance of delta = 622 ppm, consistent with an
      S(3)(N,O) or unusual upfield-shifted S(4) complex. The Pb(II) complex reveals two
      prominent absorption bands at 350 nm (epsilon = 4000 M(-1) cm(-1)) and 250 nm
      (epsilon = 41 000 M(-1) cm(-1)), spectral properties consistent with three or
      four thiolate ligands to the Pb(II) ion. The change in the anisotropy of a
      fluorescein-labeled oligonucleotide containing the cad O/P upon binding CadC and
      analyzed using a dissociable CadC dimer binding model reveals that apo-CadC forms
      a high-affinity complex [K(a) = (1.1 +/- 0.3) x 10(9) M(-1); pH 7.0, 0.40 M NaCl,
      25 degrees C], the affinity of which is reduced approximately 300-fold upon the
      binding of a single molar equivalent of Cd(II) or Pb(II). The implications of
      these findings on the mechanism of metalloregulation are discussed.

PMID- 11284700
TI  - Interaction of protein kinase C isozymes with Rho GTPases.
AB  - Evidence is provided for direct protein-protein interactions between protein
      kinase C (PKC) alpha, betaI, betaII, gamma, delta, epsilon, and zeta and members
      of the Rho family of small GTPases. Previous investigations, based on the
      immunoprecipitation approach, have provided evidence consistent with a direct
      interaction, but this remained to be proven. In the study presented here, an in
      vitro assay, consisting only of purified proteins and the requisite PKC
      activators and cofactors, was used to determine the effects of Rho GTPases on the
      activities of the different PKC isoforms. It was found that the activity of
      PKCalpha was potently enhanced by RhoA and Cdc42 and to a lesser extent by Rac1,
      whereas the effects on the activities of PKCbetaI, -betaII, -gamma, -delta, 
      epsilon, and -zeta were much reduced. These results indicate a direct interaction
      between PKCalpha and each of the Rho GTPases. However, the Rho GTPase
      concentration dependencies for the potentiating effects on PKCalpha activity
      differed for each Rho GTPase and were in the following order: RhoA > Cdc42 >
      Rac1. PKCalpha was activated in a phorbol ester- and Ca(2+)-dependent manner.
      This was reflected by a substantial decrease in the phorbol ester concentration
      requirements for activity in the presence of Ca(2+), which for each Rho GTPase
      was induced within a low nanomolar phorbol ester concentration range. The
      activity of PKCalpha also was found to be dependent on the nature of the GTP- or
      GDP-bound state of the Rho GTPases, suggesting that the interaction may be
      regulated by conformational changes in both PKCalpha and Rho GTPases. Such an
      interaction could result in significant cross-talk between the distinct pathways
      regulated by these two signaling elements.

PMID- 11284701
TI  - All-trans-retinal forms a visible-absorbing pigment with human rod opsin.
AB  - Rhodopsin activation elicits transmembrane currents due to electrostatic events
      associated with conformational changes. We employed the sensitive rhodopsin early
      receptor current approach to reevaluate whether all-trans-retinal can form a
      visual pigment with rod opsin apoprotein. An opsin shift above 440 nm is induced
      in the action spectrum of charge motions caused by visible flashes in cells
      expressing human rod opsin and regenerated with all-trans-retinal, compared to
      cells without opsin. Near-ultraviolet stimulation of opsin regenerated with all
      trans-retinal promotes charge motions similar to those arising from the meta-II
      signaling state while photochemically regenerating a pigment with ground state
      charge motion properties. These results indicate that all-trans-retinal can form
      a visual pigment with opsin, through both protonated and unprotonated Schiff base
      linkages and likely within the native ligand binding pocket at lysine-296. The
      agonist effects of all-trans-retinal may relate to its structural accommodation
      within the core of opsin, similar to other G-protein-coupled receptors.

PMID- 11284702
TI  - A novel inhibitor of the mammalian peptide transporter PEPT1.
AB  - This study was initiated to develop inhibitors of the intestinal H(+)/peptide
      symporter. We provide evidence that the dipeptide derivative Lys[Z(NO(2))]-Pro is
      an effective competitive inhibitor of mammalian PEPT1 with an apparent binding
      affinity of 5-10 microM. Characterization of the interaction of Lys[Z(NO(2))]-Pro
      with the substrate binding domain of PEPT1 has been performed in (a) monolayer
      cultures of human Caco-2 cells expressing PEPT1, (b) transgenic Pichia pastoris
      cells expressing PEPT1, and (c) Xenopus laevis oocytes expressing PEPT1. By
      competitive uptake studies with radiolabeled dipeptides, HPLC analysis of
      Lys[Z(NO(2))]-Pro in cells, and electrophysiological techniques, we unequivocally
      show that Lys[Z(NO(2))]-Pro binds with high affinity to PEPT1, competes
      competitively with various dipeptides for uptake into cells, but is not
      transported itself. Lack of transport was substantiated by the absence of
      Lys[Z(NO(2))]-Pro in Caco-2 cell extracts as determined by HPLC analysis, and by
      the absence of any positive inward currents in oocytes when exposed to the
      inhibitor. The fact that Lys[Z(NO(2))]-Pro can bind to PEPT1 from the
      extracellular as well as the intracellular site was shown in the oocyte
      expression system by a strong inhibition of dipeptide-induced currents under
      voltage clamp conditions. Our findings serve as a starting point for the
      identification of the substrate binding domain in the PEPT1 protein as well as
      for studies on the physiological and pharmacological role of PEPT1.

PMID- 11284703
TI  - Molecular mechanisms of the functional coupling of the helicase (gp41) and
      polymerase (gp43) of bacteriophage T4 within the DNA replication fork.
AB  - Processive strand-displacement DNA synthesis with the T4 replication system
      requires functional "coupling" between the DNA polymerase (gp43) and the helicase
      (gp41). To define the physical basis of this functional coupling, we have used
      analytical ultracentrifugation to show that gp43 is a monomeric species at
      physiological protein concentrations and that gp41 and gp43 do not physically
      interact in the absence of DNA, suggesting that the functional coupling between
      gp41 and gp43 depends significantly on interactions modulated by the replication
      fork DNA. Results from strand-displacement DNA synthesis show that a minimal gp41
      gp43 replication complex can perform strand-displacement synthesis at
      approximately 90 nts/s in a solution containing poly(ethylene glycol) to drive
      helicase loading. In contrast, neither the Klenow fragment of Escherichia coli
      DNA polymerase I nor the T7 DNA polymerase, both of which are nonprocessive
      polymerases, can carry out strand-displacement DNA synthesis with gp41,
      suggesting that the functional helicase-polymerase coupling may require the
      homologous system. However, we show that a heterologous helicase-polymerase pair
      can work if the polymerase is processive. Strand-displacement DNA synthesis using
      the gp41 helicase with the T4 DNA polymerase holoenzyme or the phage T7 DNA
      polymerase-thioredoxin complex, both of which are processive, proceeds at the
      rate of approximately 250 nts/s. However, replication fork assembly is less
      efficient with the heterologous helicase-polymerase pair. Therefore, a processive
      (homologous or heterologous) "trailing" DNA polymerase is sufficient to improve
      gp41 processivity and unwinding activity in the elongation stage of the helicase
      reaction, and specific T4 helicase-polymerase coupling becomes significant only
      in the assembly (or initiation) stage.

PMID- 11284704
TI  - Editing by a tRNA synthetase: DNA aptamer-induced translocation and hydrolysis of
      a misactivated amino acid.
AB  - Aminoacyl-tRNA synthetases establish the rules of the genetic code by
      aminoacylation reactions. Occasional activation of the wrong amino acid can lead
      to errors of protein synthesis. For isoleucyl-tRNA synthetase, these errors are
      reduced by tRNA-dependent hydrolytic editing reactions that occur at a site 25 A
      from the active site. These reactions require that the misactivated amino acid be
      translocated from the active site to the center for editing. One mechanism
      describes translocation as requiring the mischarging of tRNA followed by a
      conformational change in the tRNA that moves the amino acid from one site to the
      other. Here a specific DNA aptamer is investigated. The aptamer can stimulate
      amino acid-specific editing but cannot be aminoacylated. Although the aptamer
      could in principle stimulate hydrolysis of a misactivated amino acid by an
      idiosyncratic mechanism, the aptamer is shown here to induce translocation and
      hydrolysis of misactivated aminoacyl adenylate at the same site as that seen with
      the tRNA cofactor. Thus, translocation to the site for editing does not require
      joining of the amino acid to the nucleic acid. Further experiments demonstrated
      that aptamer-induced editing is sensitive to aptamer sequence and that the
      aptamer is directed to a site other than the active site or tRNA binding site of
      the enzyme.

PMID- 11284705
TI  - The binding of bis-ANS to the isolated GroEL apical domain fragment induces the
      formation of a folding intermediate with increased hydrophobic surface not
      observed in tetradecameric GroEL.
AB  - The extent of hydrophobic exposure upon bis-ANS binding to the functional apical
      domain fragment of GroEL, or minichaperone (residues 191-345), was investigated
      and compared with that of the GroEL tetradecamer. Although a total of seven
      molecules of bis-ANS bind cooperatively to this minichaperone, most of the
      hydrophobic sites were induced following initial binding of one to two molecules
      of probe. From the equilibrium and kinetics studies at low bis-ANS
      concentrations, it is evident that the native apical domain is converted to an
      intermediate conformation with increased hydrophobic surfaces. This intermediate
      binds additional bis-ANS molecules. Tyrosine fluorescence detected denaturation
      demonstrated that bis-ANS can destabilize the apical domain. The results from (i)
      bis-ANS titrations, (ii) urea denaturation studies in the presence and absence of
      bis-ANS, and (iii) intrinsic tyrosine fluorescence studies of the apical domain
      are consistent with a model in which bis-ANS binds tightly to the intermediate
      state, relatively weakly to the native state, and little to the denatured state.
      The results suggest that the conformational changes seen in apical domain
      fragments are not seen in the intact GroEL oligomer due to restrictions imposed
      by connections of the apical domain to the intermediate domain and suppression of
      movement due to quaternary structure.

PMID- 11284706
TI  - Guanidine-induced equilibrium unfolding of a homo-hexameric enzyme 4
      oxalocrotonate tautomerase (4-OT).
AB  - 4-Oxalocrotonate tautomerase (4-OT) is a bacterial enzyme that is comprised of 6
      identical 62 amino acid subunits. The 4-OT enzyme is an attractive model system
      in which to study the interrelationship between protein folding, subunit
      assembly, and catalytic function. Here we report on the GuHCl-induced equilibrium
      unfolding properties of wild-type 4-OT using catalytic activity measurements and
      using far-UV circular dichroism (CD) spectroscopy. We demonstrate that the
      unfolding of wild-type 4-OT in 50 mM phosphate buffers containing 6 M GuHCl is
      reversible at pHs 6.0, 7.4, and 8.5; and we find that there is both an enzyme
      concentration dependence and a pH dependence to the equilibrium unfolding
      properties of 4-OT. Our data suggests that the GuHCl-induced unfolding of 4-OT in
      50 mM phosphate buffer at pH 8.5 can be modeled as a two-state process involving
      folded hexamer and unfolded monomer. On the basis of this model, we determined a
      free-energy value for the unfolding of 4-OT at pH 8.5 to be 68.7 +/- 3.2 kcal/mol
      under standard state conditions (1 M hexamer). In 50 mM phosphate buffers at pHs
      6.0 and 7.4, only the catalytic activity denaturation curves are consistent with
      a two-state folding mechanism. At the lower pHs the far-UV-CD transitions are not
      well described by a two-state model. Our results at pHs 6.0 and 7.4 suggest that
      intermediate state(s) are populated in the equilibrium unfolding reaction at
      these lower pHs and that these intermediate state(s) have some helical content
      but no measurable catalytic activity.

PMID- 11284707
TI  - Complete amino acid sequence of kaouthiagin, a novel cobra venom
      metalloproteinase with two disintegrin-like sequences.
AB  - The primary structure of kaouthiagin, a metalloproteinase from the venom of the
      cobra snake Naja kaouthia which specifically cleaves human von Willebrand factor
      (VWF), was determined by amino acid sequencing. Kaouthiagin is composed of 401
      amino acid residues and one Asn-linked sugar chain. The sequence is highly
      similar to those of high-molecular mass snake venom metalloproteinases from
      viperid and crotalid venoms comprised of metalloproteinase, disintegrin-like, and
      Cys-rich domains. The metalloproteinase domain had a zinc-binding motif
      (HEXXHXXGXXH), which is highly conserved in the metzincin family. Kaouthiagin had
      an HDCD sequence in the disintegrin-like domain and uniquely had an RGD sequence
      in the Cys-rich domain. Metalloproteinase-inactivated kaouthiagin had no effect
      on VWF-induced platelet aggregation but still had an inhibitory effect on the
      collagen-induced platelet aggregation with an IC(50) of 0.2 microM, suggesting
      the presence of disintegrin-like activity in kaouthiagin. To examine the effects
      of these HDCD and RGD sequences, we prepared synthetic peptides cyclized by an S
      S linkage. Both the synthetic cyclized peptides from the disintegrin-like domain
      and from the Cys-rich domain) had an inhibitory effect on collagen-induced
      platelet aggregation with IC(50) values of approximately 90 and approximately 4.5
      microM, respectively. The linear peptide (RAAKHDCDLPELC) and the cyclized peptide
      had little effect on collagen-induced platelet aggregation. These results suggest
      that kaouthiagin not only inhibits VWF-induced platelet aggregation by cleaving
      VWF but also disturbs the agonist-induced platelet aggregation by both the
      disintegrin-like domain and the RGD sequence in the Cys-rich domain. Furthermore,
      our results imply that the corresponding part of the Cys-rich domain in other
      snake venom metalloproteinases also has a synergistic disturbing effect on
      platelet aggregation, serving as a second disintegrin-like domain. This is the
      first report of an elapid venom metalloproteinase with two disintegrin-like
      sequences.

PMID- 11284708
TI  - A novel PCNA-binding motif identified by the panning of a random peptide display
      library.
AB  - Proliferating cell nuclear antigen (PCNA) has recently been identified as a
      target for the binding of proteins involved in DNA replication, DNA repair, and
      cell cycle control. The interactions between PCNA and a number of these proteins
      are known to be mediated by a conserved peptide motif. In this study, a random
      peptide library in which peptide sequences are displayed on the E. coli bacterial
      flagellin protein was screened for PCNA-binding sequences. Analysis of the
      retrieved peptide sequences verified the presence of the known PCNA-binding
      motif. In addition, a second, larger group of peptides containing a different
      consensus sequence for PCNA binding was discovered. This sequence was found to be
      present on DNA polymerase delta, and a peptide conforming to this sequence was
      demonstrated to bind to PCNA. Database search and analysis show that many
      proteins contain the second consensus sequence. These include proteins that are
      involved in DNA replication, repair, and cell cycle control. The demonstration of
      this second PCNA-binding motif may provide a basis for identifying and
      experimentally testing specific proteins for the structural basis for PCNA
      binding.

PMID- 11284709
TI  - Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2:
      structure-activity relationships and simulation of rate constants of individual
      steps in catalysis.
AB  - Human cytochrome P450 (P450) 1A2 is involved in the oxidation of many important
      drugs and carcinogens. The prototype substrate phenacetin is oxidized to an
      acetol as well as the O-dealkylation product [Yun, C.-H., Miller, G. P., and
      Guengerich, F. P. (2000) Biochemistry 39, 11319-11329]. In an effort to improve
      rates of catalysis of P450 1A2 enzymes, we considered a set of p
      alkoxyacylanilide analogues of phenacetin and found that variations in the O
      alkyl and N-acyl substituents altered the rates of the two oxidation reactions
      and the ratio of acetol/phenol products. Moving one methylene group of phenacetin
      from the O-alkyl group to the N-acyl moiety increased rates of both oxidations
      approximately 5-fold and improved the coupling efficiency (oxidation products
      formed/NADPH consumed) from 6% to 38%. Noncompetitive kinetic deuterium isotope
      effects of 2-3 were measured for all O-dealkylation reactions examined with wild
      type P450 1A2 and the E225I mutant, which has 6-fold higher activity. A trend of
      decreasing kinetic deuterium isotope effect for E225I > wild-type > mutant D320A
      was observed for O-demethylation of p-methoxyacetanilide, which follows the trend
      for k(cat). The set of O-dealkylation and acetol formation results for wild-type
      P450 1A2 and the E225I mutant with several of the protiated and deuterated
      substrates were fit to a model developed for the basic catalytic cycle and a set
      of microscopic rate constants in which the only variable was the rate of product
      formation (substrate oxygenation, including hydrogen abstraction). In this model,
      k(cat) is considerably less than any of the microscopic rate constants and is
      affected by several individual rate constants, including the rate of formation of
      the oxygenating species, the rate of substrate oxidation by the oxygenating
      species, and the rates of generation of reduced oxygen species (H(2)O(2), H(2)O).
      This analysis of the effects of the individual rate constants provides a
      framework for consideration of other P450 reactions and rate-limiting steps.

PMID- 11284710
TI  - Cellular functions of phosphatidylinositol 3-phosphate and FYVE domain proteins.
AB  - PtdIns3P is a phosphoinositide 3-kinase product that has been strongly implicated
      in regulating membrane trafficking in both mammalian and yeast cells. PtdIns3P
      has been shown to be specifically located on membranes associated with the
      endocytic pathway. Proteins that contain FYVE zinc-finger domains are recruited
      to PtdIns3P-containing membranes. Structural information is now available
      concerning the interaction between FYVE domains and PtdIns3P. A number of
      proteins have been identified which contain a FYVE domain, and in this review we
      discuss the functions of PtdIns3P and its FYVE-domain-containing effector
      proteins in membrane trafficking, cytoskeletal regulation and receptor
      signalling.

PMID- 11284711
TI  - The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and
      degradation of mutant tyrosinases results in a lack of pigmentation.
AB  - Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disease resulting
      from mutations of the tyrosinase gene (TYR). To elucidate the molecular basis of
      OCA1 phenotypes, we analysed the early processing and maturation of several
      different types of mutant tyrosinase with various degrees of structural
      abnormalities (i.e. two large deletion mutants, two missense mutants that
      completely destroy catalytic function and three missense mutants that have a
      temperature-sensitive phenotype). When expressed in COS7 cells, all mutant
      tyrosinases were sensitive to endoglycosidase H digestion, and immunostaining
      showed their localization in the endoplasmic reticulum (ER) and their failure to
      be sorted further to their target organelles. Pulse-chase experiments showed that
      all mutant tyrosinases were retained by calnexin in the ER and that they were
      degraded at similarly rapid rates, which coincided with their dissociation from
      calnexin. Temperature-sensitive mutant enzymes were sorted more efficiently at 31
      degrees C than at 37 degrees C, and their degradation was accelerated at 37
      degrees C compared with 31 degrees C. Thus in contrast to the current concept
      that mutant tyrosinases are transported to melanosomes but are functionally
      inactive there, our results suggest that mutant tyrosinases may not be
      transported to melanosomes in the first place. We conclude that a significant
      component of mutant tyrosinase malfunction in OCA1 results from their retention
      and degradation in the ER compartment. This quality-control process is highly
      sensitive to minimal changes in protein folding, and so even relatively minor
      mutations in peripheral sequences of the enzyme not involved with catalytic
      activity may result in a significant reduction of functional enzyme in
      melanosomes.

PMID- 11284712
TI  - Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2)
      develop fragile skin and male sterility.
AB  - Transgenic mice were prepared with inactive alleles for procollagen N-proteinase
      (ADAMTS-2; where ADAMTS stands for a disintegrin and metalloproteinase with
      thrombospondin repeats). Homozygous mice were grossly normal at birth, but after
      1-2 months they developed thin skin that tore after gentle handling. Although the
      gene was inactivated, a large fraction of the N-propeptides of type I procollagen
      in skin and the N-propeptides of type II procollagen in cartilage were cleaved.
      Therefore the results suggested the tissues contained one or more additional
      enzymes that slowly process the proteins. Electron microscopy did not reveal any
      defects in the morphology of collagen fibrils in newborn mice. However, in two
      month-old mice, the collagen fibrils in skin were seen as bizarre curls in cross
      section and the mean diameters of the fibrils were approx. half of the controls.
      Although a portion of the N-propeptides of type II procollagen in cartilage were
      not cleaved, no defects in the morphology of the fibrils were seen by electron
      microscopy or by polarized-light microscopy. Female homozygous mice were fertile,
      but male mice were sterile with a marked decrease in testicular sperm. Therefore
      the results indicated that ADAMTS-2 plays an essential role in the maturation of
      spermatogonia.

PMID- 11284713
TI  - Genomic organization and characterization of splice variants of the human
      histamine H3 receptor.
AB  - In the present paper we report the genomic organization of the human histamine H3
      receptor gene, which consists of four exons spanning 5.5 kb on chromosome 20.
      Using PCR, six alternative splice variants of the H3 receptor were cloned from
      human thalamus. These variants were found to be coexpressed in human brain, but
      their relative distribution varied in a region-specific manner. These isoforms
      displayed either a deletion in the putative second transmembrane domain (TM),
      H3(DeltaTM2, 431aa) or a variable deletion in the third intracellular loop (i3),
      H3(Deltai3, 415aa), H3(Deltai3, 365aa), H3(Deltai3, 329aa) and
      H3(DeltaTM5+Deltai3, 326aa). In order to determine the biological role of the H3
      receptor variants compared with the 'original' H3(445aa) receptor, three
      isoforms, namely H3(445aa), H3(DeltaTM2, 431aa) and H3(Deltai3, 365aa), were
      expressed in CHO cells and their pharmacological properties were investigated.
      Binding studies showed that H3(DeltaTM2, 431aa) transiently expressed in CHO
      cells was unable to bind [125I]iodoproxyfan, whereas both the H3(445aa) and
      H3(Deltai3, 365aa) receptors displayed a high affinity for [125I]iodoproxyfan
      [K(d)=28+/-5 pM (n=4) and 8+/-1 pM (n=5) respectively]. In addition, H3(Deltai3,
      365aa) possessed the same pharmacological profile as the H3(445aa) receptor.
      However, in CHO cells expressing H3(Deltai3, 365aa), H3 agonists did not inhibit
      forskolin-induced cAMP production, stimulate [35S]guanosine 5'-[gamma
      thio]triphosphate ([35S]GTP[S]) binding or stimulate intracellular Ca(2+)
      mobilization. Therefore the 80-amino-acid sequence located at the C-terminal
      portion of i3 plays an essential role in H3 agonist-mediated signal transduction.
      The existence of multiple H3 isoforms with different signal transduction
      capabilities suggests that H3-mediated biological functions might be tightly
      regulated through alternative splicing mechanisms.

PMID- 11284714
TI  - Conserved C-terminal residues within the lectin-like domain of LOX-1 are
      essential for oxidized low-density-lipoprotein binding.
AB  - Lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) is a cell
      surface endocytosis receptor for atherogenic oxLDL, which is highly expressed in
      endothelial cells. Recent studies suggest that it may play significant roles in
      atherogenesis. LOX-1 is a type-II membrane protein that structurally belongs to
      the C-type lectin family molecules. This study was designed to characterize the
      specific domain on LOX-1 that recognizes oxLDL. Truncation of the lectin domain
      of LOX-1 abrogated oxLDL-binding activity. Deletion of the utmost C-terminal ten
      amino acid residues (261-270) was enough to disrupt the oxLDL-binding activity.
      Substitutions of Lys-262 and/or Lys-263 with Ala additively attenuated the
      activity. Serial-deletion analysis showed that residues up to 265 are required
      for the expression of minimal binding activity, although deletion of the C
      terminal three residues (268-270) still retained full binding activity.
      Consistently, these alterations in LOX-1 impaired the recognition by a
      functionally blocking monoclonal antibody for LOX-1. These data demonstrated the
      distinct role of the lectin domain as the functional domain recognizing LOX-1
      ligand. The conserved C-terminal residues of lectin-like domain are essential for
      binding oxLDL. Particularly, the basic amino acid pair is important for the
      binding.

PMID- 11284715
TI  - Identification and characterization of a novel sucrose-non-fermenting protein
      kinase/AMP-activated protein kinase-related protein kinase, SNARK.
AB  - Subtraction hybridization after the exposure of keratinocytes to ultraviolet
      radiation identified a differentially expressed cDNA that encodes a protein of
      630 amino acid residues possessing significant similarity to the catalytic domain
      of the sucrose-non-fermenting protein kinase (SNF1)/AMP-activated protein kinase
      (AMPK) family of serine/threonine protein kinases. Northern blotting and reverse
      transcriptase-mediated PCR demonstrated that mRNA transcripts for the SNF1/AMPK
      related kinase (SNARK) were widely expressed in rodent tissues. The SNARK gene
      was localized to human chromosome 1q32 by fluorescent in situ hybridization.
      SNARK was translated in vitro to yield a single protein band of approx. 76 kDa;
      Western analysis of transfected baby hamster kidney (BHK) cells detected two
      SNARK-immunoreactive bands of approx. 76-80 kDa. SNARK was capable of
      autophosphorylation in vitro; immunoprecipitated SNARK exhibited
      phosphotransferase activity with the synthetic peptide substrate HMRSAMSGLHLVKRR
      (SAMS) as a kinase substrate. SNARK activity was significantly increased by AMP
      and 5-amino-4-imidazolecarboxamide riboside (AICAriboside) in rat keratinocyte
      cells, implying that SNARK might be activated by an AMPK kinase-dependent
      pathway. Furthermore, glucose deprivation increased SNARK activity 3-fold in BHK
      fibroblasts. These findings identify SNARK as a glucose- and AICAriboside
      regulated member of the AMPK-related gene family that represents a new candidate
      mediator of the cellular response to metabolic stress.

PMID- 11284717
TI  - Purification and characterization of thiol-reagent-sensitive glycerol-3-phosphate
      acyltransferase from the membrane fraction of an oleaginous fungus.
AB  - Glycerol-3-phosphate acyltransferase (GPAT), responsible for the first committed,
      rate-limiting, step of glycerolipid synthesis, was purified to homogeneity from
      the membrane fraction of an oleaginous fungus, Mortierella ramanniana var.
      angulispora. The enzyme was solubilized from the membrane fraction by
      pretreatment with 0.05% Triton X-100 and treatment of the resulting pellet with
      0.3% Triton X-100. The enzyme was subsequently purified by column chromatography
      on heparin-Sepharose, Yellow 86 agarose, a second heparin-Sepharose column,
      Superdex-200 and hydroxylapatite Bio-Gel. Enzyme activity was finally enriched
      1308-fold over that of the starting membrane fraction. SDS/PAGE of the purified
      fraction revealed a single band with a molecular mass of 45 kDa. Native PAGE
      showed a major band that corresponded to GPAT activity. Enzyme activity was
      inhibited by thiol reagents, suggesting that it originated from microsomes rather
      than mitochondria. Purified GPAT depended on exogenous oleoyl-CoA and sn-glycerol
      3-phosphate, with the highest activity at approx. 50 and 250 microM,
      respectively, and preferred oleoyl-CoA 5.4-fold over palmitoyl-CoA as an acyl
      donor. Anionic phospholipids, such as phosphatidic acid and phosphatidylserine,
      were absolutely required for activity of the purified enzyme, and their ability
      to activate GPAT was influenced by the purity of the GPAT preparation. Bivalent
      cations, such as Mg(2+) and Ca(2+), inhibited purified GPAT activity, whereas 5
      mM Mn(2+) elevated activity approx. 2-fold. These results provide new insights
      into the molecular characterization of microsomal GPAT, which has not been well
      characterized compared with mitochondrial and plastidic GPAT.

PMID- 11284716
TI  - Differential effects of oncostatin M and leukaemia inhibitory factor expression
      in astrocytoma cells.
AB  - The effects of the production of two closely related cytokines, oncostatin M
      (OSM) and leukaemia inhibitory factor (LIF), by astrocytoma cells were
      investigated using the stable cell line human U373-MG, which expressed and
      secreted both biologically active polypeptides. The expression of LIF by these
      cells caused resistance to this cytokine due to loss of the LIF receptor (LIFR),
      from the cell surface, suggesting its retention. In contrast, cells expressing
      OSM were stimulated by this cytokine, utilizing an autocrine mechanism, and
      possessed receptors for OSM, but not LIF, on the cell surface. In these cells the
      continuous up-regulation of OSM-induced gene expression was found even though the
      Janus kinase-signal transducer and activator of transcription ('JAK/STAT')
      pathway was almost exhausted due to long-term autocrine stimulation of the cells
      by OSM. The amount of LIFR was down-regulated in both LIF- and OSM-producing
      cells and this effect was not found in wild-type U373-MG cells treated with
      externally added cytokines. To investigate the mechanism of autocrine stimulation
      by OSM we constructed a stable cell line expressing a form of OSM that is
      retained in the endoplasmic reticulum (ER). This biologically active cytokine was
      not secreted, but was localized in the ER. In addition, it did not stimulate the
      astrocytoma cells in an autocrine manner. We conclude that expression of LIF
      causes resistance of astrocytoma cells to this cytokine, whereas expression of
      OSM leads to autocrine stimulation.

PMID- 11284718
TI  - Thioacylation is required for targeting G-protein subunit G(o1alpha) to detergent
      insoluble caveolin-containing membrane domains.
AB  - alpha-Subunits of heterotrimeric G(i)-like proteins (alpha(i), alpha(o) and
      alpha(z)) associate with the cytoplasmic leaflet of the plasma membrane by means
      of N-terminally linked myristic acid and palmitic acid. An additional role for
      palmitate has been recently suggested by the observation that fusion with the
      palmitoylated N-terminus of alpha(i1) relocalizes cytosolic green-fluorescent
      protein reporter to low buoyancy, Triton-insoluble membrane domains (TIFF; Triton
      insoluble floating fraction), enriched with caveolin-1 [Galbiati, Volonte, Meani,
      Milligan, Lublin, Lisanti and Parenti (1999) J. Biol. Chem 274, 5843-5850]. Here
      we show that, upon transient expression in transfected COS-7 cells, myristoylated
      and palmitoylated alpha(o) (alpha(o)wt, where wt is wild-type) is exclusively
      found in TIFF, from where non-palmitoylated alpha(o)wt and alpha(o)C3S (Cys(3)-
      >Ser) mutant are excluded. Moreover, alpha(o) fused to N-terminally truncated
      human vasopressin V2 receptor (V2TR-alpha(o)), lacking myristate and palmitate,
      still localizes at the plasma membrane by means of first transmembrane helix of
      V2R, but is excluded from TIFF. Likewise, alpha(o)C3S does not partition into
      TIFF, even when its membrane avidity is enhanced by co-expression of betagamma
      subunits. Thus membrane association, in the absence of added palmitate, is not
      sufficient to confer partitioning of alpha(o) within TIFF, suggesting that
      palmitoylation is a signal for membrane compartmentalization of dually acylated
      alpha-subunits.

PMID- 11284719
TI  - Mechanism of malarial haem detoxification inhibition by chloroquine.
AB  - The haem detoxification pathway of the malaria parasite Plasmodium falciparum is
      a potential biochemical target for drug development. Free haem, released after
      haemoglobin degradation, is polymerized by the parasite to form haemozoin
      pigment. Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2) has been
      implicated as the catalytic scaffold for detoxification of haem in the malaria
      parasite. Previously we have shown that a hexapeptide repeat sequence (Ala-His
      His-Ala-Ala-Asp), which appears 33 times in Pfhrp-2, may be the major haem
      binding site in this protein. The haem binding studies carried out by ourselves
      indicate that up to 18 equivalents of haem could be bound by this protein with an
      observed K(d) of 0.94 microM. Absorbance spectroscopy provides evidence that
      chloroquine is capable of extracting haem bound to Pfhrp-2. This was supported by
      the K(d) value, of 37 nM, observed for the haem-chloroquine complex. The native
      PAGE studies reveal that the formation of the haem-Pfhrp-2 complex is disrupted
      by chloroquine. These results indicate that chloroquine may be acting by
      inhibiting haem detoxification/binding to Pfhrp-2. Moreover, the higher affinity
      of chloroquine for haem than Pfhrp-2 suggests a possible mechanism of action for
      chloroquine; it may remove the haem bound to Pfhrp-2 and form a complex that is
      toxic to the parasite.

PMID- 11284720
TI  - Cloning and rational mutagenesis of kexstatin I, a potent proteinaceous inhibitor
      of Kex2 proteinase.
AB  - Kexstatin I is a potent proteinaceous inhibitor of Kex2 proteinase (EC
      3.4.21.61). In the present study we show the molecular cloning, primary structure
      determination and expression of the gene encoding kexstatin I. We also
      demonstrate its enhanced activity and specificity for Kex2 proteinase inhibition
      by rational mutagenesis. The cloned kexstatin I gene encoded a protein of 145
      amino acid residues, including the 35-residue signal sequence for secretion. The
      amino acid sequence showed 52% identity with those of the Streptomyces subtilisin
      inhibitors (SSIs). Thus kexstatin I is the first SSI-family member that can
      inhibit Kex2 proteinase. The reactive site of the inhibitor was determined to be 
      Thr(69)-Lys(70) downward arrowGlu(71)-, where downward arrow indicates the
      reactive site. Because Kex2 proteinase generally shows the highest affinity for
      substrates with basic amino acid residues at the P(1) and P(2) sites, conversion
      of the Thr(69)-Lys(70) segment of the inhibitor into dibasic motifs was expected
      to result in enhanced inhibitory activities. Thus we constructed kexstatin I
      mutants, in which the Thr(69)-Lys(70) sequence was replaced by the Thr(69)
      Arg(70), Lys(69)-Lys(70) and Lys(69)-Arg(70) sequences using PCR-based
      mutagenesis, and analysed them kinetically. Among these mutants, the Lys(69)
      Arg(70) mutant was the most potent inhibitor. The K(i) for Kex2 proteinase was
      3.2x10(-10) M, which was 140-fold lower than that of the inhibitor with the
      Thr(69)-Lys(70) sequence. Although kexstatin I could also inhibit subtilisin, the
      enhancement of inhibitory activity upon such mutations was specific for Kex2
      proteinase inhibition.

PMID- 11284721
TI  - Phosphorylation of murine double minute clone 2 (MDM2) protein at serine-267 by
      protein kinase CK2 in vitro and in cultured cells.
AB  - Murine double minute clone 2 oncoprotein (MDM2) is a key component in the
      regulation of the tumour suppressor p53. MDM2 mediates the ubiqutination of p53
      in the capacity of an E3 ligase and targets p53 for rapid degradation by the
      proteasome. Stress signals which impinge on p53, leading to its activation,
      promote disruption of the p53-MDM2 complex, as in the case of ionizing radiation,
      or block MDM2 synthesis and thereby reduce cellular MDM2 levels, as in the case
      of UV radiation. It is therefore likely that MDM2, which is known to be modified
      by ubiquitination, SUMOylation and multi-site phosphorylation, may itself be a
      target for stress signalling (SUMO is small ubiquitin-related modifier-1). In the
      present study we show that, like p53, the MDM2 protein is a substrate for
      phosphorylation by the protein kinase CK2 (CK2) in vitro. CK2 phosphorylates a
      single major site, Ser(267), which lies within the central acidic domain of MDM2.
      Fractionation of cellular extracts revealed the presence of a single Ser(267)
      protein kinase which co-purified with CK2 on ion-exchange chromatography and,
      like CK2, was subject to inhibition by micromolar concentrations of the CK2
      specific inhibitor 5,6-dichlororibofuranosylbenzimidazole. Radiolabelling of
      cells expressing tagged recombinant wild-type MDM2 or a S267A (Ser(267)-->Ala)
      mutant, followed by phosphopeptide analysis, confirmed that Ser(267) is a
      cellular target for phosphorylation. Ser(267) mutants are still able to direct
      the degradation of p53, but in a slightly reduced capacity. These data highlight
      a potential route by which one of several physiological modifications occurring
      within the central acidic domain of the MDM2 protein can occur.

PMID- 11284722
TI  - Heat-shock protein 90 augments neuronal nitric oxide synthase activity by
      enhancing Ca2+/calmodulin binding.
AB  - Heat-shock protein 90 (hsp90) has been shown to facilitate neuronal NO synthase
      (nNOS, type 1) activity in vivo. But the direct effect of hsp90 on purified nNOS
      has not been determined yet. Moreover, the mechanism underlying the action of
      hsp90 is not known. nNOS activity is primarily initiated and regulated by the
      binding of Ca(2+)/calmodulin (CaM). Therefore, we explored whether hsp90
      modulates nNOS activity by affecting CaM binding. Recombinant rat nNOS was
      purified from the stably transfected cells by affinity chromatography. hsp90
      increased nNOS activity in a dose-dependent manner with an EC(50) of 24.1+/-6.4
      nM. In the presence of hsp90, the CaM-nNOS dose-response curve was shifted
      markedly to the left and the maximal activity was also elevated. Further in vitro
      protein-binding experiments confirmed that hsp90 increased the binding of CaM to
      nNOS. Taken together, these data indicate that hsp90 directly augments nNOS
      catalytic function and that this effect is, at least partially, mediated by CaM
      binding enhancement.

PMID- 11284723
TI  - Up-regulation of steroid sulphatase activity in HL60 promyelocytic cells by
      retinoids and 1alpha,25-dihydroxyvitamin D3.
AB  - HL60 promyeloid cells express both classes of oestrogen receptor (ERalpha and
      ERbeta). We show that hydrolysis of oestrone sulphate by steroid sulphatase is a
      major source of oestrone in HL60 cells, and that most of the released oestrone is
      not metabolized further to 17beta-oestradiol. Treatment of HL60 cells with
      retinoids or 1alpha,25-dihydroxyvitamin D3 increased steroid sulphatase mRNA and
      activity in parallel with the induction of CD11b, an early marker of myeloid
      differentiation that is expressed before the differentiating cells stop
      proliferating. Use of agonists and antagonists against retinoid receptor-alpha
      and retinoid receptor-X revealed that both classes of retinoid receptor can drive
      steroid sulphatase up-regulation. Steroid sulphatase activity fluctuates during
      the cell cycle, being highest around the transition from G1 to S phase. During
      the differentiation of HL60 cells induced by all-trans-retinoic acid or 1alpha,25
      dihydroxyvitamin D3, there is increased conversion of 17beta-oestradiol into
      oestrone by an oxidative 17beta-hydroxysteroid dehydrogenase. Treatment of Caco-2
      colon adenocarcinoma cells with all-trans-retinoic acid or 1alpha,25
      dihydroxyvitamin D3 also increases 17beta-oestradiol oxidation to oestrone. An
      increase in local oestrone production therefore occurs in multiple cell types
      following treatment with retinoids and 1alpha,25-dihydroxyvitamin D3. The
      possible involvement of locally produced oestrogenic steroids in regulating the
      proliferation and differentiation of myeloid cells is discussed.

PMID- 11284724
TI  - Influence of phenylalanine-481 substitutions on the catalytic activity of
      cytochrome P450 2D6.
AB  - Homology models of the active site of cytochrome P450 2D6 (CYP2D6) have
      identified phenylalanine 481 (Phe(481)) as a putative ligand-binding residue, its
      aromatic side chain being potentially capable of participating in pi-pi
      interactions with the benzene ring of ligands. We have tested this hypothesis by
      replacing Phe(481) with tyrosine (Phe(481)-->Tyr), a conservative substitution,
      and with leucine (Phe(481)-->Leu) or glycine (Phe(481)-->Gly), two non-aromatic
      residues, and have compared the properties of the wild-type and mutant enzymes in
      microsomes prepared from yeast cells expressing the appropriate cDNA-derived
      protein. The Phe(481)-->Tyr substitution did not alter the kinetics [K(m)
      (microM) and V(max) (pmol/min per pmol) respectively] of oxidation of S
      metoprolol (27; 4.60), debrisoquine (46; 2.46) or dextromethorphan (2; 8.43)
      relative to the respective wild-type values [S-metoprolol (26; 3.48),
      debrisoquine (51; 3.20) and dextromethorphan (2; 8.16)]. The binding capacities
      [K(s) (microM)] of a range of CYP2D6 ligands to the Phe(481)-->Tyr enzyme (S
      metoprolol, 22.8; debrisoquine, 12.5; dextromethorphan, 2.3; quinidine, 0.13)
      were also similar to those for the wild-type enzyme (S-metoprolol, 10.9;
      debrisoquine, 8.9; dextromethorphan, 3.1; quinidine, 0.10). In contrast, the
      Phe(481)-->Leu and Phe(481)-->Gly substitutions increased significantly (3-16
      fold) the K(m) values of oxidation of the three substrates [S-metoprolol (120-124
      microM), debrisoquine (152-184 microM) and dextromethorphan (20-31 microM)].
      Similarly, the K(s) values of the ligands to Phe(481)-->Leu and Phe(481)-->Gly
      mutants were also increased 3 to 10-fold (S-metoprolol, 33.2-41.9 microM;
      debrisoquine, 85-90 microM; dextromethorphan, 15.7-18.8 microM; quinidine 0.35
      0.53 microM). However, contrary to a recent proposal that Phe(481) has the
      dominant role in the binding of substrates that undergo CYP2D6-mediated N
      dealkylation routes of metabolism, the Phe(481)-->Gly substitution did not
      substantially decrease the capacity of the enzyme to N-deisopropylate metoprolol
      (wild-type, 1.12 pmol/min per pmol of P450; Phe(481)-->Gly, 0.71), whereas an
      Asp(301)-->Gly substitution decreased the N-dealkylation reaction by 95% of the
      wild-type rate. Overall, our results are consistent with the proposal that
      Phe(481) is a ligand-binding residue in the active site of CYP2D6 and that the
      residue interacts with ligands via a pi-pi interaction between its phenyl ring
      and the aromatic moiety of the ligand. However, the relative importance of
      Phe(481) in binding is ligand-dependent; furthermore, its importance is secondary
      to that of Asp(301). Finally, contrary to predictions of a recent homology model,
      Phe(481) does not seem to have a primary role in CYP2D6-mediated N-dealkylation.

PMID- 11284725
TI  - Cloning and characterization of a fourth human lysyl oxidase isoenzyme.
AB  - We report here the complete cDNA sequence and exon-intron organization of the
      human lysyl oxidase-like (LOXL)3 gene, a new member of the lysyl oxidase (LO)
      gene family. The predicted polypeptide is 753 amino acids in length, including a
      signal peptide of 25 residues. The C-terminal region, residues 529-729, contains
      a LO domain similar to those in the LOX (the first characterized LO isoenzyme),
      LOXL and LOXL2 polypeptides. It possesses the putative copper binding sequence,
      and the lysine and tyrosine residues that form the lysyltyrosyl quinone cofactor.
      The N-terminal region, which is similar to that in LOXL2 but not those in LOX and
      LOXL, contains four subregions similar to scavenger receptor cysteine-rich
      domains and a putative nuclear localization signal. Recombinant LOXL3, expressed
      in HT-1080 cells, was secreted into the culture medium but was not detected by
      immunofluorescence staining in nuclei. The LOXL3 mRNA is 3.1 kb in size and is
      expressed in many tissues, the highest levels among the tissues studied being
      seen in the placenta, heart, ovary, testis, small intestine and spleen.

PMID- 11284726
TI  - Hierarchies of ATP-consuming processes: direct compared with indirect
      measurements, and comparative aspects.
AB  - The original aim of the present study was to deal with two problems that had
      emerged from a study on hierarchies of ATP-consuming processes in cells
      [Buttgereit and Brand (1995) Biochem. J. 312, 163-167]. Firstly, we wanted to
      find out whether the results of that study had been influenced by the method used
      for the determination of process activity and, secondly, we wondered whether and
      to what extent the structure of the hierarchy established for cell suspensions
      under energy-limiting conditions might depend on the type of cell or on the
      lifestyle, ecology and phylogenetic status of the species from which the cells
      were derived. We confined our study to the two most prominent ATP consumers of
      cells: protein synthesis and the Na(+)/K(+)-ATPase, measuring their activity
      directly by [3H]leucine incorporation and Rb(+)-flux respectively. We found large
      differences in the sensitivity of protein synthesis to energy limitation between
      hepatocytes from an anoxia-tolerant fish species and an anoxia-sensitive fish
      species (goldfish and rainbow trout respectively). On the other hand, Na(+)/K(+)
      ATPase activity was hardly affected by energy limitation in the hepatocytes from
      both fish species. We also studied the response of a human hepatoma cell line,
      HepG2, to energy limitation and found both protein synthesis and Na(+)/K(+)
      ATPase activity to be equally sensitive to energy limitation, but more sensitive
      than the Na(+)/K(+)-ATPase of the two fish species. A comparison of the indirect
      and direct methods for measuring protein synthesis revealed the rate of oxygen
      consumption to be functionally related to the concentration of cycloheximide, the
      inhibitor used. It was found that at 15 mM cycloheximide [three orders of
      magnitude higher than the concentration at which the incorporation of free amino
      acids (FAA) into protein is inhibited] total oxygen consumption was suppressed by
      71-75%, whereas the measured rate of [3H]leucine incorporation into protein
      suggested that the cycloheximide-sensitive fraction should have amounted to not
      more than approx. 10% of the total oxygen consumption. On the other hand, the
      amount of oxygen consumption suppressed with the high concentration of
      cycloheximide corresponded almost exactly to the increase in oxygen consumption
      of cells incubated in an FAA-enriched medium compared with cells incubated in a
      standard, FAA-free medium. Our major conclusions are, firstly, that high
      concentrations of cycloheximide disrupt cellular metabolism, bringing to a
      standstill all those processes that can be stimulated by incubating starved cells
      in an FAA-enriched medium, secondly, that the attempt to estimate the metabolic
      cost of protein synthesis by inhibiting oxygen consumption with cycloheximide
      leads to spurious results, and, thirdly, that the structure of a 'hierarchy' of
      ATP-consumers may reflect the lifestyle and physiology of the species studied.

PMID- 11284727
TI  - Interaction of plasminogen with dipeptidyl peptidase IV initiates a signal
      transduction mechanism which regulates expression of matrix metalloproteinase-9
      by prostate cancer cells.
AB  - Both plasminogen (Pg) activation and matrix metalloproteinases (MMPs) are
      involved in the proteolytic degradation of extracellular matrix components, a
      requisite event for malignant cell metastasis. The highly invasive 1-LN human
      prostate tumour cell line synthesizes and secretes large amounts of Pg activators
      and MMPs. We demonstrate here that the Pg type 2 (Pg 2) receptor in these cells
      is composed primarily of the membrane glycoprotein dipeptidyl peptidase IV (DPP
      IV). Pg 2 has six glycoforms that differ in their sialic acid content. Only the
      highly sialylated Pg 2gamma, Pg 2delta and Pg 2epsilon glycoforms bind to DPP IV
      via their carbohydrate chains and induce a Ca(2+) signalling cascade; however, Pg
      2epsilon alone is also able to significantly stimulate expression of MMP-9. We
      further demonstrate that the Pg-mediated invasive activity of 1-LN cells is
      dependent on the availability of Pg 2epsilon. This is the first demonstration of
      a direct association between the expression of MMP-9 and the Pg activation
      system.

PMID- 11284728
TI  - Recruitment of coat-protein-complex proteins on to phagosomal membranes is
      regulated by a brefeldin A-sensitive ADP-ribosylation factor.
AB  - Particle internalization in macrophages is followed by a complex maturation
      process. We have previously observed that proteins bound to phagocytosed
      particles are sorted from phagosomes into a heterogeneous population of vesicles
      that fuse with endosomes. However, the mechanism and the protein machinery
      involved in the formation of these phagosome-derived vesicles are largely
      unknown. It has been shown that vesicles coated with coat protein complex type I
      (COPI) have a role in both secretion and endocytosis. To address the possibility
      that COPI proteins might participate in the formation of phagosome-derived
      vesicles we studied the recruitment of beta-COP to highly purified phagosomes.
      The binding of beta-COP to phagosomal membranes was regulated by nucleotides and
      inhibited by brefeldin A (BFA). An ADP-ribosylation factor 1 (ARF1) mutant
      defective in GTP hydrolysis supported the binding of beta-COP to phagosomes
      independently of added nucleotide. AlF(4) and Gbetagamma subunits, agents known
      to modulate heterotrimeric G-protein activity, were tested in the beta-COP
      binding assay. AlF(4) increased beta-COP association, whereas binding was
      inhibited by the addition of Gbetagamma subunits. Our results suggest that COP
      proteins are recruited to phagosomal membranes by a mechanism that involves
      heterotrimeric GTP-binding proteins and a BFA-sensitive ARF. In addition, our
      findings indicate that COPI proteins are involved in the recycling of components
      from phagosomes to the cell surface.

PMID- 11284729
TI  - Differences in tissue-specific and embryonic expression of mouse Ceacam1 and
      Ceacam2 genes.
AB  - The intercellular adhesion molecule CEACAM1, also known as C-CAM1 (where CAM is
      cell-adhesion molecule), can function as a tumour suppressor in several
      carcinomas, including those of the prostate, breast, bladder and colon. This
      suggests that CEACAM1 may play an important role in the regulation of normal cell
      growth and differentiation. However, there is no direct evidence to support this
      putative function of CEACAM1. To elucidate its physiological function by targeted
      gene deletion, we isolated the Ceacam genes from a mouse 129 Sv/Ev library.
      Although there is only one Ceacam1 gene in humans and one in rats, two homologous
      genes (Ceacam1 and Ceacam2) have been identified in the mouse. Our sequence
      analysis revealed that the genes encoded nine exons and spanned approx. 16-17 kb
      (Ceacam1) and 25 kb (Ceacam2). The genes were highly similar (79.6%). The major
      differences in the protein-coding regions were located in exons 2, 5 and 6
      (76.9%, 87.0% and 78.5% similarity respectively). In addition, introns 2, 5 and 7
      were also significantly different, being 29.7%, 59.8% and 64.5% similar
      respectively. While most of these differences were due to nucleotide
      substitutions, two insertions of 418 and 5849 bp occurred in intron 2 of Ceacam2,
      and another two insertions of 1384 and 197 bp occurred in introns 5 and 7
      respectively. To determine whether functional redundancy exists between Ceacam1
      and Ceacam2, we examined their expression in 16 mouse tissues by using semi
      quantitative reverse transcription-PCR. As in human and rat, in the mouse Ceacam1
      mRNA was highly abundant in the liver, small intestine, prostate and spleen. In
      contrast, Ceacam2 mRNA was only detected in kidney, testis and, to a lesser
      extent, spleen. Reverse transcription-PCR using testis RNA indicated that Ceacam2
      in the testis is an alternatively spliced form containing only exons 1, 2, 5, 6,
      8 and 9. In the mouse embryo, Ceacam1 mRNA was detected at day 8.5, disappeared
      between days 9.5 and 12.5, and re-appeared at day 19. On the other hand, no
      Ceacam2 mRNA was detected throughout embryonic development. The different tissue
      expression patterns and regulation during embryonic development suggest that the
      CEACAM1 and CEACAM2 proteins, although highly similar, may have different
      functions both during mouse development and in adulthood.

PMID- 11284730
TI  - Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early
      concepti.
AB  - Indoleamine 2,3-dioxygenase (IDO)-initiated tryptophan degradation in the
      placenta has been implicated in the prevention of the allogeneic fetus rejection
      [Munn, Zhou, Attwood, Bondarev, Conway, Marshall, Brown, and Mellor (1998)
      Science 281, 1191-1193]. To determine how IDO is associated with the development
      of the fetus and placenta, the time course of IDO expression (tryptophan
      degrading activity, IDO protein and IDO mRNA) in the embryonic and extra
      embryonic tissues as well as maternal tissues of mice was examined. A high
      tryptophan-degrading activity was detected in early concepti on days 6.5 and 7.5,
      whereas IDO protein and its mRNA were not expressed during early gestation, but
      appeared 2-3 days later, lasted for about 3 days and declined rapidly thereafter.
      The expression of IDO basically coincided with the formation of the placenta. On
      the contrary, the early tryptophan-degrading activity was due to gene expression
      of tryptophan 2,3-dioxygenase (TDO), as shown by Northern and Western analysis.
      These findings indicate that IDO is transiently expressed in the placenta but
      that the expression does not last until birth, and that the IDO expression is
      preceded by expression of another tryptophan-degrading enzyme, TDO, in the
      maternal and/or embryonic tissues in early concepti.

PMID- 11284731
TI  - Identification and characterization of UDP-N-acetylenolpyruvylglucosamine
      reductase (MurB) from the Gram-positive pathogen Streptococcus pneumoniae.
AB  - The UDP-N-acetylenolpyruvylglucosamine reductase (MurB) from a Gram-positive
      pathogen, Streptococcus pneumoniae, was identified and characterized. The enzyme
      from S. pneumoniae shows 31% identity with the MurB protein from Escherichia
      coli, and contains the catalytic residues, substrate-binding residues and FAD
      binding motif identified previously in the E. coli protein. The gene was cloned
      into the pET28a+ expression vector, and the 34.5 kDa protein that it encodes was
      overexpressed in E. coli strain BL21(DE3) to 30% of total cell protein. The
      majority of the protein was found to be insoluble. A variety of methods were used
      to increase the amount of soluble protein to 10%. This was then purified to near
      homogeneity in a two-step process. The absorption spectrum of the purified
      protein indicated it to be a flavoprotein, like its E. coli homologue, with a
      characteristic absorption at 463 nm. The enzyme was shown to be active, reducing
      UDP-N-acetylglucosamine enolpyruvate with the concomitant oxidation of NADPH, and
      was characterized kinetically with respect to its two substrates. The enzyme
      showed properties similar to those of its E. coli counterpart, being activated by
      univalent cations and being subject to substrate inhibition. The characterization
      of an important cell wall biosynthesis enzyme from a Gram-positive pathogen
      provides a good starting point for the discovery of antibacterial agents against
      MurB.

PMID- 11284732
TI  - p38 mitogen-activated kinase is a bidirectional regulator of human fibroblast
      collagenase-1 induction by three-dimensional collagen lattices.
AB  - When fibroblasts are cultured in contracting collagen matrices, matrix
      metalloproteinase-1 (MMP-1, collagenase-1) is induced. In the present study we
      demonstrate that p38alpha mitogen-activated protein kinase (p38alpha MAPK) plays
      a bi-directional role in the MMP-1 response to contracting floating collagen
      lattices (fl-coll). fl-coll, but not attached collagen lattices (att-coll), co
      ordinately increased expression of MMP-1 and activities of p38alpha and MKK3/6
      (MAPK kinase 3/6). However, treatment of primary fibroblasts cultured in fl-coll
      with increasing doses of SB203580, an inhibitor of p38alpha and p38beta, caused a
      bipolar pattern of MMP-1 expression. Partial inhibition of p38 MAPK activity
      resulted in the lowest level of MMP-1 expression, whereas total inhibition of p38
      activity led to MMP-1 levels as high as in the absence of inhibitor. The
      activation/inhibition of p38alpha was apparently responsible for the observed
      phenomena, as supported by three lines of evidence. (1) p38alpha was the
      predominant isoform sensitive to SB203580 in primary fibroblasts. (2) Fibroblasts
      transfected with increasing dose of a dominant negative p38alpha (p38DN)
      similarly demonstrated the bipolar pattern of MMP-1 expression induced by fl
      coll. (3) The bipolar MMP-1 expression occurred during the gradual, linear
      inhibition of p38alpha kinase activity by both inhibitors, SB203580 and p38DN.
      Nuclear factor-kappaB (NF-kappaB), a previously identified positive regulator of
      MMP-1 expression induced by fl-coll [Xu, Zutter, Santoro and Clark (1998) J. Cell
      Biol. 140, 709-719] was mediated by fl-coll-activated p38alpha. However, the fl
      coll-induced expression of MMP-1 facilitated by p38alpha suppression was
      maintained independent of NF-kappaB activity, suggesting the existence of a
      p38alpha-dependent antagonistic pathway. We conclude that fl-coll-induced MMP-1
      expression is the net outcome of opposing effects mediated by p38alpha.
      Therefore, the level of p38alpha kinase activity may provide a fine-tuned control
      of MMP-1 gene expression in response to biomechanical signals.

PMID- 11284733
TI  - Detection of phospholipid oxidation in oxidatively stressed cells by reversed
      phase HPLC coupled with positive-ionization electrospray [correction of
      electroscopy] MS.
AB  - Measurement of lipid peroxidation is a commonly used method of detecting
      oxidative damage to biological tissues, but the most frequently used methods,
      including MS, measure breakdown products and are therefore indirect. We have
      coupled reversed-phase HPLC with positive-ionization electrospray MS (LC-MS) to
      provide a method for separating and detecting intact oxidized phospholipids in
      oxidatively stressed mammalian cells without extensive sample preparation. The
      elution profile of phospholipid hydroperoxides and chlorohydrins was first
      characterized using individual phospholipids or a defined phospholipid mixture as
      a model system. The facility of detection of the oxidized species in complex
      mixtures was greatly improved compared with direct-injection MS analysis, as they
      eluted earlier than the native lipids, owing to the decrease in hydrophobicity.
      In U937 and HL60 cells treated in vitro with t-butylhydroperoxide plus Fe(2+),
      lipid oxidation could not be observed by direct injection, but LC-MS allowed the
      detection of monohydroperoxides of palmitoyl-linoleoyl and stearoyl-linoleoyl
      phosphatidylcholines. The levels of hydroperoxides observed in U937 cells were
      found to depend on the duration and severity of the oxidative stress. In cells
      treated with HOCl, chlorohydrins of palmitoyloleoyl phosphatidylcholine were
      observed by LC-MS. The method was able to detect very small amounts of oxidized
      lipids compared with the levels of native lipids present. The membrane-lipid
      profiles of these cells were found to be quite resistant to damage until high
      concentrations of oxidants were used. This is the first report of direct
      detection by LC-MS of intact oxidized phospholipids induced in cultured cells
      subjected to oxidative stress.

PMID- 11284734
TI  - Telomerase is regulated by protein kinase C-zeta in human nasopharyngeal cancer
      cells.
AB  - Telomerase, a specialized ribonucleoprotein reverse transcriptase that directs
      the synthesis of telomeric DNA, is repressed in normal human somatic cells, but
      is activated in most cancers. Little is known concerning how telomerase activity
      is activated and maintained in cancer cells. We have shown previously that
      inhibition of protein kinase C (PKC) decreases the telomerase activity of human
      nasopharyngeal carcinoma (NPC) cells. Here, we provide evidence that the decrease
      of telomerase activity by PKC inhibition is not mediated by transcriptional down
      regulation of hTERT, the catalytic protein of human telomerase. In vitro
      phosphorylation studies revealed that exogenous addition of PKC-alpha, -betaI, 
      delta or -zeta led to restoration of telomerase activity in the crude extracts of
      PKC-inhibited NPC cells. However, depletion of PKC-alpha and -betaI in vivo had
      no detectable effect on the telomerase activity of NPC cells. Using antisense
      oligonucleotides against individual PKC isotypes, we observed that telomerase
      activity was inhibited only by the antisense oligonucleotide against PKC-zeta but
      not by those against PKC-alpha, -betaI or -delta. Taken together, these data
      demonstrate that PKC participates in the regulation of telomerase activity by
      direct or indirect phosphorylation of telomerase proteins, and that PKC-zeta is
      the PKC isotype that functions in vivo in the NPC cells.

PMID- 11284735
TI  - Modulation of epidermal growth factor receptor phosphorylation by endogenously
      expressed gangliosides.
AB  - The effect of changing the ganglioside composition of Chinese hamster ovary K1
      cells on the function of the epidermal growth factor receptor (EGFr) was examined
      by studying the signalling pathway generated after the binding of epidermal
      growth factor (EGF) both in cells depleted of glycosphingolipids by inhibiting
      glucosylceramide synthase activity and in cell lines expressing different
      gangliosides as the result of stable transfection of appropriate ganglioside
      glycosyltransferases. After stimulation with EGF, cells depleted of glycolipids
      showed EGFr phosphorylation and extracellular signal-regulated protein kinase 2
      (ERK2) activity as parental cells expressing GM3 [ganglioside nomenclature
      follows Svennerholm (1963) J. Neurochem. 10, 613-623] or as transfected cells
      expressing mostly GM2 and GD1a as the result of stable transfection of UDP
      GalNAc:LacCer/GM3/GD3 N-acetylgalactosaminyltransferase. However, cells stably
      transfected with CMP-NeuAc:GM3 sialyltransferase and expressing GD3 at the cell
      surface showed both decreased EGFr phosphorylation and ERK2 activation after
      stimulation with EGF. Results suggest that changes in the ganglioside composition
      of cell membranes might be important in the regulation of the EGF signal
      transduction.

PMID- 11284736
TI  - Influence of metallothionein-1 localization on its function.
AB  - Metallothioneins (MTs) have a major role to play in metal metabolism, and may
      also protect DNA against oxidative damage. MT protein has been found localized in
      the nucleus during S-phase. The mRNA encoding the MT-1 isoform has a perinuclear
      localization, and is associated with the cytoskeleton; this targeting, due to
      signals within the 3'-untranslated region (3'-UTR), facilitates nuclear
      localization of MT-1 during S-phase [Levadoux, Mahon, Beattie, Wallace and
      Hesketh (1999) J. Biol. Chem. 274, 34961-34966]. Using cells transfected with MT
      gene constructs differing in their 3'-UTRs, the role of MT protein in the nucleus
      has been studied. Chinese hamster ovary cells were transfected with either the
      full MT gene (MTMT cells) or with the MT 5'-UTR and coding region linked to the
      3'-UTR of glutathione peroxidase (MTGSH cells). Cell survival following exposure
      to oxidative stress and chemical agents was higher in cells expressing the native
      MT gene than in cells where MT localization was disrupted, or in untransfected
      cells. Also, MTMT cells showed less DNA damage than MTGSH cells in response to
      either hydrogen peroxide or mutagen. After exposure to UV light or mutagen, MTMT
      cells showed less apoptosis than MTGSH cells, as assessed by DNA fragmentation
      and flow cytometry. The data indicate that the perinuclear localization of MT
      mRNA is important for the function of MT in a protective role against DNA damage
      and apoptosis induced by external stress.

PMID- 11284737
TI  - Differential involvement of peroxisome-proliferator-activated receptors alpha and
      delta in fibrate and fatty-acid-mediated inductions of the gene encoding liver
      fatty-acid-binding protein in the liver and the small intestine.
AB  - Liver fatty-acid-binding protein (L-FABP) is a cytoplasmic polypeptide that binds
      with strong affinity especially to long-chain fatty acids (LCFAs). It is highly
      expressed in both the liver and small intestine, where it is thought to have an
      essential role in the control of the cellular fatty acid (FA) flux. Because
      expression of the gene encoding L-FABP is increased by both fibrate
      hypolipidaemic drugs and LCFAs, it seems to be under the control of transcription
      factors, termed peroxisome-proliferator-activated receptors (PPARs), activated by
      fibrate or FAs. However, the precise molecular mechanism by which these
      regulations take place remain to be fully substantiated. Using transfection
      assays, we found that the different PPAR subtypes (alpha, gamma and delta) are
      able to mediate the up-regulation by FAs of the gene encoding L-FABP in vitro.
      Through analysis of LCFA- and fibrate-mediated effects on L-FABP mRNA levels in
      wild-type and PPARalpha-null mice, we have found that PPARalpha in the intestine
      does not constitute a dominant regulator of L-FABP gene expression, in contrast
      with what is known in the liver. Only the PPARdelta/alpha agonist GW2433 is able
      to up-regulate the gene encoding L-FABP in the intestine of PPARalpha-null mice.
      These findings demonstrate that PPARdelta can act as a fibrate/FA-activated
      receptor in tissues in which it is highly expressed and that L-FABP is a
      PPARdelta target gene in the small intestine. We propose that PPARdelta
      contributes to metabolic adaptation of the small intestine to changes in the
      lipid content of the diet.

PMID- 11284739
TI  - GTP cyclohydrolase I mRNA: novel splice variants in the slime mould Physarum
      polycephalum and in human monocytes (THP-1) indicate conservation of mRNA
      processing.
AB  - GTP cyclohydrolase I (EC 3.5.4.16) is the first enzyme in the biosynthesis of
      tetrahydrobiopterin [(6R)-5,6,7,8-tetrahydro-L-biopterin, H(4)-biopterin] in
      mammals and of folic acid in bacteria. Here we have characterized the GTP
      cyclohydrolase I gene structure and two mRNA species from Physarum polycephalum,
      an acellular slime mould that synthesizes H(4)-biopterin and metabolites of the
      folic acid biosynthetic pathway. Its GTP cyclohydrolase I gene consists of seven
      exons, and the two GTP cyclohydrolase I cDNA species isolated from Physarum
      encode for proteins with 228 (25.7 kDa) and 195 (22.1 kDa) amino acids.
      Furthermore, we identified two previously undescribed mRNA species in interferon
      gamma-treated human myelomonocytoma cells (THP-1) in addition to the cDNA coding
      for the fully functional 250-residue (27.9 kDa) protein, which is identical with
      that in human phaeochromocytoma cells. One of the new splice variants codes for a
      233-residue (25.7 kDa) protein, whereas the other codes for the full-length
      protein but is alternatively spliced within the 3'-untranslated region. In
      heterologous expression, the shorter proteins of Physarum as well as of THP-1
      cells identified here are degraded by proteolysis. Accordingly, only the 27.9 kDa
      protein was detectable in Western blots from THP-1 cell extracts. Quantification
      of GTP cyclohydrolase I mRNA species in different human cell types with and
      without cytokine treatment showed that in addition to the correct mRNA the two
      splice variants isolated here, as well as the two splice variants known from
      human liver, are strongly induced by cytokines in cell types with inducible GTP
      cyclohydrolase I (THP-1, dermal fibroblasts), but not in cell types with
      constitutive GTP cyclohydrolase I expression (SK-N-SH, Hep-G2). As in human
      liver, splicing of the new mRNA variant found in THP-1 cells occurs at the
      boundary of exons 5 and 6. Strikingly, the 195-residue protein from Physarum is
      alternatively spliced at a homologous position, i.e. at the boundary of exons 6
      and 7. Thus alternative splicing of GTP cyclohydrolase I at this position occurs
      in two species highly distant from each other in terms of evolution. It remains
      to be seen whether variant proteins encoded by alternatively spliced GTP
      cyclohydrolase I mRNA transcripts do occur in vivo and whether they participate
      in regulation of enzyme activity.

PMID- 11284738
TI  - Identification, characterization and leucocyte expression of Siglec-10, a novel
      human sialic acid-binding receptor.
AB  - Here we characterize Siglec-10 as a new member of the Siglec family of sialic
      acid-binding Ig-like lectins. A full-length cDNA was isolated from a human spleen
      library and the corresponding gene identified. Siglec-10 is predicted to contain
      five extracellular Ig-like domains and a cytoplasmic tail containing three
      putative tyrosine-based signalling motifs. Siglec-10 exhibited a high degree of
      sequence similarity to CD33-related Siglecs and mapped to the same region, on
      chromosome 19q13.3. The expressed protein was able to mediate sialic acid
      dependent binding to human erythrocytes and soluble sialoglycoconjugates. Using
      specific antibodies, Siglec-10 was detected on subsets of human leucocytes
      including eosinophils, monocytes and a minor population of natural killer-like
      cells. The molecular properties and expression pattern suggest that Siglec-10 may
      function as an inhibitory receptor within the innate immune system.

PMID- 11284740
TI  - cyp7b1 catalyses the 7alpha-hydroxylation of dehydroepiandrosterone and 25
      hydroxycholesterol in rat prostate.
AB  - Dehydroepiandrosterone (DHEA) is the most prominent circulating steroid in
      humans, and it is a precursor for sex-steroid synthesis in peripheral tissues,
      including the prostate. Recently, enzyme-mediated pre-receptor metabolism has
      been recognized as a key step in determining steroid action in vivo.
      Hydroxylation of 3beta-steroids at the 7alpha-position has been reported in rat
      and human prostate to be a major inhibitory pathway to sex-steroid
      synthesis/action. However, the molecular identity of the enzyme responsible is so
      far unknown. We recently described a novel cytochrome P450 enzyme, cyp7b1,
      strongly expressed in the hippocampus of rodent brain, which catalyses the
      metabolism of DHEA, pregnenolone and 25-hydroxycholesterol to 7alpha-hydroxy
      products. In the light of this new enzyme, we have examined its possible role in
      7alpha-hydroxylation conversion in rat prostate. NADPH-dependent 7alpha
      hydroxylation was confirmed for 3beta-hydroxysteroids including DHEA and
      androstenediol, as well as 25-hydroxycholesterol. Kinetic analysis yielded an
      apparent K(m) of 14+/-1 microM for 7alpha-hydroxylation of DHEA in the prostate
      gland, a value similar to that recorded for recombinant cyp7b1 enzyme [13.6
      microM; Rose, Stapleton, Dott, Kieny, Best, Schwarz, Russell, Bjoorkheim, Seckl
      and Lathe (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 4925-4930]. The V(max) value
      of the prostate was 46+/-2 pmol/min per mg, and this activity was inhibited by
      clotrimazole, a P450-enzyme blocker. Moreover, RNA analysis (reverse
      transcription PCR, Northern blotting and in situ hybridization) revealed a high
      expression of cyp7b1 mRNA in the rat prostate, restricted to the epithelium,
      suggesting that cyp7b1 catalyses oxysterol 7alpha-hydroxylation in the prostate
      gland.

PMID- 11284741
TI  - Epidermal transformation leads to increased perlecan synthesis with heparin
      binding-growth-factor affinity.
AB  - Perlecan, a proteoglycan of basement membrane and extracellular matrices, has
      important roles in both normal biological and pathological processes. As a result
      of its ability to store and protect growth factors, perlecan may have crucial
      roles in tumour-cell growth and invasion. Since the biological functions of
      different types of glycosaminoglycan vary with cellular origin and structural
      modifications, we analysed the expression and biological functions of perlecan
      produced by a normal epidermal cell line (JB6) and its transformed counterpart
      (RT101). Expression of perlecan in tumorigenic cells was significantly increased
      in both mRNA and protein levels. JB6 perlecan was exclusively substituted with
      heparan sulphate, whereas that of RT101 contained some additional chondroitin
      sulphate. Detailed structural analysis of the heparan sulphate (HS) chains from
      perlecan of both cell types revealed that their overall sulphation and chain
      length were similar (approximately 60 kDa), but the HS chains of tumour-cell
      derived perlecan were less sulphated. This resulted from reduced 2-O- and 6-O
      sulphation, but not N-sulphation, and an increase in the proportion of
      unsulphated disaccharides. Despite this, the heparan sulphate of RT101- and JB6
      derived perlecan bound fibroblast growth factor-1, -2, -4 and -7 and heparin
      binding epidermal growth factor with similar affinity. Therefore abundant tumour
      derived perlecan may support the angiogenic responses seen in vivo and be a key
      player in tumorigenesis.

PMID- 11284742
TI  - Transcriptional and translational mechanisms of cytochrome b5 reductase isoenzyme
      generation in humans.
AB  - Cytochrome b5 reductase (b5R) is an essential enzyme that exists in soluble and
      membrane-bound isoforms, each with specific functions. In the rat, the two forms
      are generated from alternative transcripts differing in the first exons. In
      contrast, the biogenesis of b5R isoforms in the human is not yet well understood.
      In the present study we have detected three novel alternative exons, designated
      1S, S' and 1B, located between the first alternative exon 1M and the common
      second exon in the human b5R gene. Accordingly, multiple M-type, S-type and SS'
      type and B-type transcripts are generated. All types of human b5R transcript are
      expressed ubiquitously. An analysis of in vitro translation products demonstrated
      an alternative use of different AUG initiators resulting in the production of
      various human b5R protein isoforms. Our results indicate that the organization of
      the 5' region of the b5R gene is not conserved between rodents and humans.
      Insertion of Alu elements into the human b5R gene, in particular just upstream of
      the S/S' region, could be responsible for dynamic events of gene rearrangement
      during evolution.

PMID- 11284744
TI  - Delivering a diagnosis of glaucoma. Are we considering the patient or only his
      eyes?

PMID- 11284743
TI  - Co-operative regulation of the transcription of human dihydrodiol dehydrogenase
      (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)
      4alpha/gamma and HNF-1alpha.
AB  - Human dihydrodiol dehydrogenase (DD) 4/aldo-keto reductase (AKR) 1C4 is a major
      isoform of hepatic DD that oxidizes trans-dihydrodiols of polycyclic aromatic
      hydrocarbons to reactive and redox-active o-quinones and that reduces several
      ketone-containing drugs. To investigate the mechanism of transcriptional
      regulation of the human DD4 gene, the 5'-flanking region of the gene was fused to
      the luciferase gene. The results of luciferase assays using HepG2 cells and of
      1,10-phenanthroline-copper footprinting indicated that two positive regulatory
      regions were located in regions from -701 to -684 and from -682 to -666. The
      former region contained a putative hepatocyte nuclear factor (HNF)-4 binding
      motif, and the latter region contained an HNF-1 consensus binding sequence. DNA
      fragments of the HNF-4 or HNF-1 motif gave a shifted band in a gel-shift assay
      with nuclear extracts from HepG2 cells. The formation of the DNA-protein complex
      was inhibited by the HNF-4 or HNF-1 motif of the alpha(1)-antitrypsin gene. A
      supershift assay using antibodies to human HNF-4alpha, HNF-4gamma and HNF-1alpha
      showed that HNF-4alpha and HNF-4gamma bound to the HNF-4 motif, and that HNF
      1alpha interacted with the HNF-1 motif. Introduction of mutations into the HNF-4
      or HNF-1 motif lowered the luciferase activity to 10 or 8% respectively of that
      seen with the intact human DD4 gene. These results indicate that HNF-4alpha, HNF
      4gamma and HNF-1alpha regulate co-operatively the transcription of the human DD4
      gene in HepG2 cells.

PMID- 11284745
TI  - Ocular perfusion and age-related macular degeneration.
AB  - PURPOSE: To review the role of ocular perfusion in the pathophysiology of age
      related macular degeneration (AMD), the leading cause of irreversible blindness
      in the industrialized world. METHODS: Medline search of the literature published
      in English or with English abstracts from 1966 to 2000 was performed using
      various combinations of relevant key words. RESULTS: Vascular defects have been
      identified in both nonexudative and exudative AMD patients using fluorescein
      angiographic methods, laser Doppler flowmetry, indocyanine green angiography, and
      color Doppler imaging. CONCLUSION: Although these studies lend some support to
      the vascular pathogenesis of AMD, it is not possible to determine if the
      choroidal perfusion abnormalities play a causative role in nonexudative AMD, if
      they are simply an association with another primary alteration, such as a primary
      RPE defect or a genetic defect at the photoreceptor level, or if they are more
      strongly associated with one particular form of this heterogeneous disease.
      Further study is warranted.

PMID- 11284746
TI  - The impact of glaucoma on the quality of life of patients in Norway. I. Results
      from a self-administered questionnaire.
AB  - PURPOSE: To evaluate the feelings and experiences of patients living with
      glaucoma. METHODS: A questionnaire was delivered to patients willing to take
      part, at a regular visit to their ophthalmologist, for filling in anonymously at
      home. A total of 589 questionnaires were returned. RESULTS: More than 80%
      reported negative emotions on learning that they had glaucoma, one-third were
      afraid of going blind. Half the patients had no visual problem at all, 14%
      complained of poor or very poor vision. This proportion increased with age. One
      fourth of the patients on topical medication experienced adverse effects of
      moderate or high degree. About half the patients being treated with laser or
      surgery felt their situation had improved afterwards. Nine-tenths of the
      individuals were satisfied with the information and care given, although their
      knowledge about glaucoma was rather incomplete. One-fifth missed information,
      mainly on causes, treatment and prognosis of the disease. The younger patients
      were more anxious and inquiring, reported more side effects and were less
      satisfied than the older patients. The women were in general more dissatisfied
      than the men. CONCLUSION: Giving a patient a diagnosis of glaucoma influences his
      quality of life negatively. Only half of our patients experienced any visual
      difficulties, whereas one-fourth reported adverse reactions due to the therapy.
      Most of the patients were very satisfied with the information and care given.
      Ophthalmologists in private practice are quite central in the management and care
      of the glaucoma patients in a medical setting like ours.

PMID- 11284747
TI  - The impact of glaucoma on the quality of life of patients in Norway. II. Patient
      response correlated to objective data.
AB  - PURPOSE: To elucidate the relationship between the visual difficulties reported
      by patients treated for glaucoma and their objective functional damage, and to
      evaluate the reliability of the patient responses. METHODS: Questionnaires
      concerning quality of life filled in at home by 589 patients treated for chronic
      open angle glaucoma were correlated to corresponding questionnaires returned from
      their ophthalmologists. RESULTS: Few of our patients had a visual field damage
      judged to be of functional significance. There was a weak to moderate association
      between both visual field defects and decreased visual acuity and self-reported
      visual difficulties. A high proportion of the patients had normal binocular
      visual field and a stable disease, raising the suspicion that some of them were
      treated for ocular hypertension. The agreement between the responses from the
      patients and the ophthalmologists concerning the topical treatment was good,
      regarding treatment duration and other diseases of the patients the agreement was
      moderate. CONCLUSION: The association between subjective visual disability and
      presence of visual field defects was weak to moderate in our patients treated for
      glaucoma, and this association was further weakened by adjusting for visual
      acuity. Some patients might be treated unnecessarily, and a favourable prognosis
      might be given to most of them. The reliability of the patients in general was
      good.

PMID- 11284748
TI  - The effect on diurnal intraocular pressure of the fixed combination of
      latanoprost 0.005% and timolol 0.5% in patients with ocular hypertension.
AB  - PURPOSE: To measure the effect on intraocular pressure (IOP) after single-dose
      administration of the fixed combination of latanoprost 0.005% and timolol 0.5%.
      METHODS: A randomized, double-masked placebo-controlled parallel-group study was
      carried out. Twenty patients with ocular hypertension received the fixed
      combination of latanoprost+timolol, while 10 received placebo eyedrops. On
      baseline day no eyedrops were given, but IOP was measured repeatedly between 8.00
      a.m. and 8.00 p.m. On Day 7 the eyedrops were given at 8.00 a.m., and IOP
      measured as on baseline day. On Day 8 and Day 9, IOP was again measured at 8.00
      a.m. RESULTS: There was no difference in IOP in the placebo group. In the
      latanoprost+timolol group maximal IOP reduction (12.4+/-2.8 mmHg; mean+/-standard
      deviation) occurred 6.4 hours after drug administration (5.2--7.7 hours; 95%
      confidence interval [CI]). The mean IOP reduction after 24 hours was 9.8 mmHg
      (7.4--12.2 mmHg; 95% CI; p<0.001), and after 48 hours 5.7 mmHg (3.4--8.1 mmHg;
      95% CI; p<0.001). CONCLUSIONS: The fixed combination of latanoprost+timolol
      statistically significantly reduced IOP after single-dose administration. The
      maximal effect was noted after about 6 hours, and the IOP reduction was still
      pronounced after 48 hours.

PMID- 11284749
TI  - Metabolic abnormalities in patients with primary open-angle glaucoma.
AB  - PURPOSE: Although there are few data on the underlying mechanisms of primary open
      angle glaucoma (POAG), it has been suggested that metabolic diseases may play a
      role in the evolution of the disease. We carried out the present study to
      investigate the involvement of metabolic disturbances in POAG pathogenesis.
      MATERIAL/METHODS: Serum metabolic parameters were evaluated in 49 POAG patients
      without a known history of diabetes mellitus and 72 age and sex matched
      individuals without glaucoma (control group). RESULTS: Among the metabolic
      parameters examined, only fasting serum glucose and uric acid levels were found
      significantly higher in patients with glaucoma compared to the control population
      (117+/-17 mg/dl vs 105+/-11 mg/dl, p=0.05 and 6.2+/-1.9 mg/dl vs 5+/-1.2 mg/dl,
      p=0.006, respectively). Additionally, a considerably greater proportion of
      patients had disturbances of the carbohydrate metabolism and hyperuricemia.
      CONCLUSION: We conclude that disturbances of carbohydrate and uric acid
      metabolism could play a role in glaucoma damage and pathogenesis.

PMID- 11284750
TI  - Strabismus and binocular function in children with Down syndrome. A population
      based, longitudinal study.
AB  - PURPOSE: We have performed a population-based, longitudinal study on strabismus
      in children with Down syndrome. The aims of the study were to examine the
      frequency and type of strabismus, the age at onset, and the binocular potential.
      METHODS: An unselected population of 60 children with Down syndrome born 1988
      1999 was followed with repeated examinations. Mean follow-up time was 55+/-23
      months (range 24--115). The alignment of the eyes was examined using Hirschberg
      corneal reflex test and cover test for near fixation. To evaluate binocular
      function, Titmus House Fly Test and Lang's stereo test were used. RESULTS: Twenty
      five patients (42%) had strabismus (21 esotropias, two exodeviations and two
      vertical deviations). Only one case of infantile esotropia was found, the other
      esotropias were acquired forms. The mean age at "onset" (e.g. when strabismus was
      first noticed) was 54+/-35 months. In the acquired esotropia group (n=20), 15
      (75%) were associated with hypermetropia (mean spherical equivalent +4.3+/-1.7
      D). Seventeen of the strabismic patients had an accommodation weakness. Eleven of
      the strabismus patients gave a clearly positive response to one or both
      stereotests. CONCLUSIONS: The majority of the Down syndrome children with
      strabismus have an acquired esotropia and hence a potential for binocularity.
      Hypermetropia and accommodation weakness are probably important factors in
      esotropia in Down syndrome patients.

PMID- 11284751
TI  - Association between visual impairment and functional and morphological cerebral
      abnormalities in full-term children.
AB  - PURPOSE: To characterise the nature and degree of ocular disorders and cerebral
      morphological and functional abnormalities in a population-based group of
      visually impaired full-term pre-school children. METHODS: Forty-five children who
      were born at full-term between 1989 and 1995 in Varmland, Sweden, were reported
      as being visually impaired. An ophthalmological examination was performed and
      clinical data regarding mental development and neurological disease were obtained
      for all children. Cerebral imaging was performed in 35 children. RESULTS: Twenty
      six per cent of the children were found to have ocular disorders only. Forty-two
      per cent had cerebral morphological abnormalities, verified by cerebral imaging,
      and 65% had signs of cerebral functional abnormalities. In total, 74% were found
      to have cerebral morphological and/or cerebral functional abnormalities.
      CONCLUSION: The majority of children with visual impairment, including children
      with ocular disorders, were found to have cerebral morphological and/or cerebral
      functional abnormalities. We suggest that any child with visual impairment should
      therefore undergo cerebral imaging and be examined by a paediatrician in order to
      establish the correct diagnosis.

PMID- 11284752
TI  - Cataract surgery and effectiveness. 2. An index approach for the measurement of
      output and efficiency of cataract surgery at different surgery departments.
AB  - PURPOSE: To describe a model for comparing the performance of cataract surgery
      among ophthalmology departments in terms of economic efficiency. METHODS: An
      index approach for the measurement of outcome of cataract surgery is modeled. The
      index approach uses information about activities and difficulties in daily life
      as well as visual acuity and age. The change in activities and difficulties after
      surgery is expressed by changes in distances, and an overall index score is
      calculated as ratios of values to distances. Values to distances are estimated as
      solutions to linear programming problems. Index scores are calculated for two
      groups of patients, those with an ocular co-morbidity and those without. Economic
      efficiency is also estimated by use of an index approach. In the estimation of
      efficiency we use the calculated index scores of outcome of surgery as a measure
      of output of the ophthalmology department. Four different departments providing
      cataract surgery are compared. RESULTS: The studied departments showed
      differences to a great extent when traditional measures of cataract surgery
      outcomes were used. These differences changed when the outcomes were compared by
      use of index scores. When economic efficiency was calculated the difference
      between the departments was further reduced and only one department was
      considered inefficient according to the model. CONCLUSION: An index approach was
      used to study outcomes of cataract surgery and economic efficiency in four
      departments. This approach takes into account the complexity of cost in relation
      to feasible outcome. The ranking between the departments described by traditional
      methods turned out differently using the model.

PMID- 11284753
TI  - Cortical lens opacification in Iceland. Risk factor analysis -- Reykjavik Eye
      Study.
AB  - PURPOSE: Cortical lens opacification has been associated with outdoor exposure
      and UV radiation more than other types of lens opacification. We studied risk
      factors for cortical lens opacification only, the most common as well as the
      earliest age related change we observe in the lens. METHODS: 1,045 persons, 583
      females and 462 males, 50 years and older, underwent a detailed eye examination
      and answered a questionnaire. Participants with cortical lens opacification grade
      I, totalling 374 persons, were assigned to case-control study I, and to case
      control study II those with cortical lens opacification grades II and III,
      totalling 82 subjects. 378 age and sex matched persons served as controls.
      RESULTS: Those who spent more than 4 hours/day outside on weekdays, in their 20's
      -30's and 40's--50's respectively, were found to have increased risk of moderate
      to severe cortical lens opacification. Thus the relative risk for grades II &
      III, was 2.80 (95% CI 1.01--7.80) and 2.91 (95% CI 1.13--9.62) respectively.
      Ageing and systemic cortical steroids use were also found to be risk factors.
      CONCLUSION: Outdoor exposure appears to be associated with increased risk of
      moderate to severe cortical lens opacification. Ageing is, however, the main risk
      factor.

PMID- 11284754
TI  - The effect of systemic hypertension on pulsatile ocular blood flow in diabetic
      patients.
AB  - PURPOSE: To determine the haemodynamics of the ciliary choroidal system in
      diabetics with or without systemic hypertension. METHODS: 90 eyes of 45 diabetic
      patients were included into the study. Patients were divided into two groups
      based on the presence of systemic hypertension. The pulsatile component of the
      total ocular blood flow in diabetics with or without hypertension was analyzed
      using ocular blood flow tonograph (OBF Labs, UK). The control group was comprised
      of 40 age-matched eyes of 20 volunteers with no ocular or systemic disease.
      Results were compared with the control group. RESULTS: Pulse amplitude (PA),
      pulse volume (PV) and pulsatile ocular blood flow (POBF) were significantly lower
      (p<0.05) in diabetics without systemic hypertension than the controls. In
      diabetics with hypertension, although the systolic and diastolic blood pressures
      were significantly higher than the control group, there was not any statistically
      significant difference (p>0.05) between PA, PV and POBF results. CONCLUSION: POBF
      was found to be lower in diabetics without hypertension compared to the controls.
      Such a presence of systemic hypertension may increase the choroidal blood flow in
      diabetics.

PMID- 11284755
TI  - Maculopathy and visual acuity in newly diagnosed type 2 diabetic patients and non
      diabetic subjects: a 10-year follow-up study.
AB  - PURPOSE: The long-term evolution of diabetic maculopathy and visual acuity and
      their risk factors in patients with newly diagnosed Type 2 diabetes and in
      control subjects. METHODS: A 10-year prospective study consisting of a
      representative group of 133 (70 men, 63 women) newly diagnosed Type 2 diabetic
      patients diagnosed at health centers between 1979 and 1981 and 144 (62 men, 82
      women) non-diabetic control subjects recruited from the population register. The
      frequency of maculopathy was determined by grading of 45 degrees fundus
      photographs and fluorescein angiograms. The subjects were studied at baseline and
      after 5 and 10 years. RESULTS: The frequency of maculopathy in Type 2 diabetic
      patients was low at the time of diagnosis but increased sharply after 5 years of
      the disease and at the 10-year examination 21% of diabetic patients had signs of
      maculopathy. By the 10-year follow-up the visual acuity declined more markedly in
      the diabetic patients than in the control subjects. Poor glycaemic control was
      the most important predictive factor for the development of maculopathy as well
      as deterioration of visual acuity. CONCLUSIONS: In newly diagnosed patients with
      Type 2 diabetes one-fifth had developed maculopathy which deteriorated their
      visual acuity. Poor glycaemic control was the most important predictor of
      maculopathy.

PMID- 11284756
TI  - The value of electrophysiology results in patients with epilepsy and vigabatrin
      associated visual field loss.
AB  - PURPOSE: To determine the value of electrophysiological findings in patients with
      temporal lobe epilepsy and to relate these findings to the amount of concentric
      contraction of the visual field and the use of vigabatrin. METHODS: Electro
      retinograms and electro-oculograms were done on 30 patients, operated for
      temporal lobe epilepsy. The patients were divided into three groups: (A)
      concentric contraction of the visual field associated with a history of
      vigabatrin medication (15 patients), (B) normal visual field with vigabatrin use
      (11 patients) and (C) normal visual field without vigabatrin medication (4
      patients). RESULTS: Electrophysiological abnormalities were found in 50% of the
      patients in group A. The Arden ratio of the EOG was lowered in 57%. Abnormalities
      in the ERG were found: b-wave implicit time photopic F was prolonged (50%), b
      wave amplitudes scotopic B (53%), C (73%) and G (50%) and photopic H (50%) were
      diminished. The amount of visual field loss and the total dose of vigabatrin
      used, showed only slight correlation with the ERG and EOG. The use of vigabatrin
      during the ERG and EOG recording in group A, gave a higher b-wave amplitude
      scotopic G in 64% of cases. The a-wave implicit times scotopic G (73%) and
      photopic G (59%) and H (73%) were shortened in group B. CONCLUSION: EOG was
      abnormal in 57% in group A. ERG abnormalities could only be found in 50% of group
      A, mainly in the inner retina. Since also the total dose of vigabatrin and the
      amount of visual field loss did not really show a correlation with the
      electrophysiological findings and results of literature are not unanimous,
      electrophysiology does not appear at present to be a good method to detect
      patients with, or at risk of, vigabatrin associated visual field loss. Regularly
      performed visual field examination remains the cornerstone in screening.

PMID- 11284758
TI  - Randomised controlled trial of ketorolac in the management of corneal abrasions.
AB  - PURPOSE: To evaluate the role of topical non-steroidal anti-inflammatory agents
      (NSAIDs) in the management of corneal abrasions with respect to symptoms and
      healing. METHODS: The study was designed as a prospective, single center,
      randomised, placebo controlled, double-blinded trial. Eighty-eight consecutive
      patients with non-infective, non-contact lens related traumatic or foreign body
      removal related corneal abrasions were recruited to this study. They were
      randomised into two groups. Both groups were given a single instillation of Gutt.
      cyclopentolate 0.5% followed by chloramphenicol eye ointment four times a day
      until the following day. In addition, the treatment group received topical
      Ketorolac trometamol 0.5% ophthalmic solution while the control group received
      placebo Liquifilm tears. Patients were assessed at presentation and about twenty
      four hours later for subjective symptoms, abrasion size and any associated
      complications. RESULTS: There was no statistical difference in the two groups at
      base line and twenty-four hour follow-up when assessed for five subjective
      symptoms of pain, photophobia, grittiness, watering and blurring of vision.
      However, those receiving topical ketorolac required significantly less additional
      oral analgesics (p=0.001). There was no difference in the rate of healing.
      CONCLUSION: Use of topical ketorolac may be a useful adjunct in the management of
      corneal abrasions.

PMID- 11284757
TI  - Adverse ocular effects of flecainide.
AB  - PURPOSE: To study if flecainide has ocular adverse effects. METHODS: Both eyes of
      38 flecainide medicated patients were thoroughly examined including colour
      vision, contrast sensitivity and visual fields. RESULTS: 10.5% of the patients
      had blurred vision on lateral gaze lasting for a couple of seconds. Small corneal
      deposits were found in 14.5% of the patients. All visual function tests were
      normal. CONCLUSION: Flecainide seems to be a safe drug with minimal ocular
      adverse effects.

PMID- 11284759
TI  - Demonstration of increasing standard pH value of lacrimal fluid with increase of
      flow rate.
AB  - PURPOSE: To test the hypothesis that pH value of human tears is affected by flow
      rate. METHODS: After stimulation with a drop of 70% alcohol into the ipsilateral
      nasal cavity tears from the left eyes of 30 healthy volunteers were collected
      with glass capillaries while flow rate of tear secretion was registered. The
      pCO(2), actual and standard pH were determined in the collected samples with the
      Astrup method: Standard pH is defined as the pH of the sample that has been
      equilibrated at 37 degrees C with a gas mixture having pCO(2)=40 mmHg. RESULTS:
      The flow rate correlated positively and significantly with both the standard pH
      value (r=0.503, p<0.01) and the pCO(2) (r=0.517, p<0.01) while there was no
      correlation between the actual pH and the flow rate. CONCLUSION: Loss of CO(2)
      from the sample is a cause of serious uncertainty in tear pH determination. A
      positive flow rate-pH relationship was found for human tears when the uncertainty
      was removed by determination of the standard pH.

PMID- 11284760
TI  - External beam irradiation therapy for choroidal haemangiomas. Visual and
      anatomical results after a dose of 20 to 25 Gy.
AB  - PURPOSE: To evaluate the visual and anatomic results of radiation therapy in ten
      patients with choroidal haemangiomas. METHODS: Nine patients with circumscribed
      choroidal haemangiomas and one with diffuse choroidal haemangioma have been
      reviewed retrospectively. They were treated by lens-sparing external beam
      radiation therapy (20--24 Gy) (9 eyes) and plaque brachytherapy (25 Gy) (1 eye),
      respectively. RESULTS: The visual acuity improved by two lines or more in 8 of 10
      eyes. No eyes showed deterioration of visual acuity. In all cases the retinal
      detachment showed complete resolution. A regression in tumour thickness was
      observed in all cases, and a reduction of anisometropia in cases with submacular
      infiltration by the tumour. During follow-up (0.4--8.8 years) there were no signs
      of radiation cataract, retinopathy or optic neuropathy. CONCLUSIONS: External
      beam radiation (20--25 Gy) is a reasonable alternative for treatment of
      symptomatic choroidal haemangiomas.

PMID- 11284761
TI  - An evaluation of the retinal nerve fiber layer thickness by scanning laser
      polarimetry in individuals with dementia of the Alzheimer type.
AB  - PURPOSE: To determine, using scanning laser polarimetry, whether or not the
      retinal nerve fiber layer (RNFL) is altered in dementia of the Alzheimer type
      (DAT). METHODS: Thirty individuals with mild to moderate DAT and 30 healthy age
      matched controls participated in the study. Fundus images were acquired with a
      Nerve Fiber Analyzer. RNFL thickness measurements were obtained under an ellipse
      located 1.75 disc diameter from the optic nerve head (ONH) center. RESULTS: No
      differences in RNFL thickness were observed between DAT and healthy subjects. The
      regional distribution of RNFL thickness was similar between the two test groups,
      with the RNFL being thickest in the superior and inferior retinal segments
      relative to the nasal and temporal regions. CONCLUSIONS: Our data indicate that
      the RNFL is not altered in DAT, at least in the earlier stages of the disease.

PMID- 11284762
TI  - Vitreoretinal surgery in Behcet's disease with severe ocular complications.
AB  - PURPOSE: To investigate effects of vitreoretinal surgery in Behcet's disease.
      MATERIALS AND METHOD: Vitreoretinal surgery was applied to 26 eyes of 21 patients
      with Behcet's disease. Preoperative and postoperative visual acuities, number and
      duration of attacks, anterior and posterior segment pathologies were evaluated.
      RESULTS: The mean age of the patients was 33 years and female/male ratio was
      6/15. The mean follow-up was 23 months. Visual acuity increased in 15 eyes (58%),
      did not change in 11 eyes (42%). In the postoperative period, there was a
      significant decrease in mean number of uveitis attacks compared to the
      preoperative period (p=0.001), as well as a significant decrease in the mean
      duration of uveitis attacks (p=0.001). In the postoperative follow-up,
      intravitreal haemorrhage in 2 eyes (8%), posterior subcapsular cataract in 5 eyes
      (19%) and corticonuclear cataract in 2 eyes (8%) were observed. Posterior
      capsular opacification (PCO) developed in 5 of 16 eyes (31%) having ECLE-IOL. CME
      continued in 3 eyes (12%). CONCLUSION: Vitreoretinal surgery has favourable
      effect on the visual and anatomic prognosis in Behcet's patients with severe
      ocular complications.

PMID- 11284763
TI  - Normative measurements of Korean orbital structures revealed by computerized
      tomography.
AB  - PURPOSE: The purposes of this study were to establish criteria for the diameters
      of normal extraocular muscles, the width of the optic nerve, and the globe
      position as revealed by CT, and to investigate the effects of age and sex on
      these parameters in the Korean population. SUBJECTS AND METHODS: Diameters of
      extraocular muscles (medial, lateral, superior complex, and inferior rectus),
      distance from the interzygomatic line to the posterior margin of the globe, width
      of the optic nerve-sheath complex, and length of the interzygomatic line were
      calculated for 214 patients on axial and direct coronal CT images, and the
      effects of age and sex were analyzed. RESULTS: Normal range for the diameters as
      given by mean+/-2SDs of extraocular muscles were medial rectus, 2.2--5.4 mm;
      lateral rectus, 2.1--4.9 mm; inferior rectus, 2.5--5.7 mm; and superior complex
      group, 2.6--6.4 mm. The mean optic nerve-sheath complex was 4.1 mm and the values
      ranged from 2.9 mm to 5.3 mm. The mean length of the interzygomatic line was
      103.8 mm. The normal posterior position of the globe as here designed was 11.2 mm
      behind the interzygomatic line (range, 6.4--15.3 mm). All parameters under study
      were a little larger in males than females. Statistically, however, there was no
      significant difference between males' and females' results, nor between the
      various age groups (p>0.05). CONCLUSION: Our CT results may help clinical
      ophthalmologists to accurately assess enlargement of the extraocular muscles and
      the optic nerve as well as aiding in the evaluation of exophthalmos.

PMID- 11284764
TI  - Rieger syndrome is associated with PAX6 deletion.
AB  - PURPOSE: Rieger syndrome is an autosomal dominant condition defined by anterior
      segment dysgenesis in combination with facial, dental, skeletal and umbilical
      abnormalities. To date Rieger syndrome has been associated with mutations in the
      PITX2 gene at chromosome 4q25 and a second locus has been found at chromosome
      13q14. METHODS: We describe a Rieger syndrome case with all the typical
      dysmorphic features and the molecular genetic finding by use of FISH analysis of
      the PAX6 gene. RESULTS: An eight-year-old girl had iris stroma hypoplasia,
      corectopia and iridogoniodysgenesis. She had an underdeveloped premaxilla and a
      congenital absence of nine teeth in the maxilla. The front teeth in the mandible
      were peg-shaped and all teeth were small. There was failure of involution of the
      periumbilical skin. FISH analysis using probes for the PAX6 gene showed a small
      deletion for the PAX6 gene on one homologue of chromosome 11. CONCLUSION: Rieger
      syndrome can -- in addition to PITX2 gene mutations and abnormalities at
      chromosome 13q14 -- be associated with PAX6 gene abnormalities.

PMID- 11284765
TI  - Corneal pathology and outcome of keratoplasty in autoimmune polyendocrinopathy
      candidiasis-ectodermal dystrophy (APECED).
AB  - BACKGROUND: Disabling, chronic, persistent keratoconjunctivitis is an essential
      ocular manifestation in autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy (APECED). PURPOSE: Because of the paucity of previous studies our aim
      is to describe the main histopathological features of the keratopathy and to
      report the long-term outcome of corneal grafting. MATERIAL: Four corneal buttons
      obtained at keratoplasties. Two patients with clinical follow-up data of 30
      years. RESULTS: The corneal epithelium showed a severe atrophy with even areas of
      incipient epidermalization. The Bowman's membrane was destroyed. The anterior
      corneal stroma was replaced by vascularized scar tissue with areas of chronic
      inflammatory cell infiltration consisting mainly of lymphocytes and plasma cells.
      The posterior corneal stroma, the Descemet's membrane and the endothelium were
      normal. Rejection occurred after each keratoplasty. The last visual acuity of the
      first patient was finger counting of the right eye and 0.3 of the left eye and of
      the second patient 0.08 of both eyes. CONCLUSION: In chronic keratopathy of
      APECED the anterior corneal layers, the epithelium, the Bowman's membrane and the
      anterior corneal stroma are affected while the posterior cornea appears normal.
      As after keratoplasty rejection may be expected, its prevention and management
      need intensive attention.

PMID- 11284766
TI  - Anthrax as the cause of preseptal cellulitis and cicatricial ectropion.
AB  - A 54-year-old female farmer with anthrax infection of the eyelids is presented.
      She was initially managed with high dose intravenous penicillin G treatment.
      Following complete healing of the eyelid lesions, significant cicatricial
      ectropion resulted. Her right lower eyelid ectropion was corrected by surgical
      reconstruction using full thickness skin graft after a period of 6 months during
      which the cicatrization process stabilized. Satisfactory cosmetic and functional
      improvement was achieved. Anthrax of the eyelid must be considered in the
      differential diagnosis of preseptal or orbital cellulitis and any reconstructive
      procedure should be attempted only after the cessation of the healing process.

PMID- 11284767
TI  - Cataract surgery and effectiveness.

PMID- 11284770
TI  - Exfoliation (pseudoexfoliation) syndrome: toward a new understanding. Proceedings
      of the First International Think Tank.
AB  - Exfoliation (pseudoexfoliation; PEX) syndrome is the single most common
      identifiable cause of open-angle glaucoma, however, very few investigators are
      engaged in basic research on this disease. To stimulate the field, the First
      International Think Tank on Exfoliation Syndrome was held in New York in July
      1999, comprising clinicians and scientists. This report is a summary of the
      proceedings of this meeting.

PMID- 11284771
TI  - Iron and inflammatory bowel disease.
AB  - Both anaemia of iron deficiency and anaemia of chronic disease are frequently
      encountered in inflammatory bowel disease. Anaemia of iron deficiency is mostly
      due to inadequate intake or loss of iron. Anaemia of chronic disease probably
      results from decreased erythropoiesis, secondary to increased levels of
      proinflammatory cytokines, reactive oxygen metabolites and nitric oxide.
      Assessment of the iron status in a condition associated with inflammation, such
      as inflammatory bowel disease, is difficult. The combination of serum transferrin
      receptor with ferritin concentrations, however, allows a reliable assessment of
      the iron deficit. The best treatment for anaemia of chronic disease is the cure
      of the underlying disease. Erythropoietin reportedly may increase haemoglobin
      levels in some of these patients. The anaemia of iron deficiency is usually
      treated with oral iron supplements. Iron supplementation may lead to an increased
      inflammatory activity through the generation of reactive oxygen species. To date,
      data from studies in animal models of inflammatory bowel disease support the
      theoretical disadvantage of iron supplementation in this respect. The results,
      however, cannot easily be extrapolated to the human situation, because the amount
      of supplemented iron in these experiments was much higher than the dose used in
      patients with iron deficiency.

PMID- 11284772
TI  - Food hypersensitivity and irritable bowel syndrome.
AB  - Irritable bowel syndrome is a common condition but its pathophysiology remains
      poorly understood. Many irritable bowel syndrome patients give a history of food
      intolerance, but data from dietary elimination and re-challenge studies are
      inconclusive. Multiple aetio-pathological mechanisms have been postulated. The
      gut has an extensive immune system but current understanding of processing of
      food antigens in health and disease is limited. There is no clinically useful
      marker available to test for food hypersensitivity in irritable bowel syndrome.
      Researchers have employed both skin tests and serum immunoglobulins (IgG and IgE)
      as markers of food hypersensitivity in various disorders including irritable
      bowel syndrome, but published data are equivocal. In this article, the evidence
      for the role of food hypersensitivity in irritable bowel syndrome is reviewed
      and, based on the available data, a possible pathophysiological hypothesis has
      been formulated.

PMID- 11284773
TI  - A molecular rationale for the how, when and why of colorectal cancer screening.
AB  - Colorectal cancer remains a leading cause of cancer-related mortality in the
      United States. Recently, colorectal cancer screening and colorectal cancer
      prevention have gained national attention. In response, the American
      Gastroenterological Association, the American College of Gastroenterology and the
      Agency for Healthcare Policy and Research have published recommendations for
      colorectal cancer screening and surveillance in patients with sporadic as well as
      hereditary forms of colorectal cancer. This review will focus on the basic
      molecular differences underlying the formation of carcinoma in patients with
      sporadic colorectal cancer, and the heritable syndromes of familial adenomatous
      polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), and juvenile
      polyposis (JPS). By appreciating the molecular mechanisms underlying these four
      types of polyp cancer syndromes, the differences in clinical time course for
      progression from polyp to carcinoma and in current screening recommendations for
      patients with sporadic adenomas, FAP, HNPCC and JPS can be better understood.

PMID- 11284774
TI  - Infliximab induces potent anti-inflammatory and local immunomodulatory activity
      but no systemic immune suppression in patients with Crohn's disease.
AB  - BACKGROUND: Anti-TNFalpha therapy with infliximab is effective for Crohn's
      disease. Infliximab neutralizes the biological activities of TNFalpha, a cytokine
      involved in host-defence against certain infections. AIM: To evaluate the effects
      of infliximab on the gut and peripheral immune system functions. METHODS:
      Biopsies and blood samples from three clinical trials of infliximab in Crohn's
      disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell
      subsets, T cell function, and cytokine profiles of lamina propria mononuclear
      cells (LPMC) and peripheral blood mononuclear cells (PBMC) were analysed.
      RESULTS: Infliximab has a serum half-life of 9.5 days and is still detectable in
      serum 8 weeks after infusion. Leucocyte counts showed consistent changes from
      baseline toward normal values after therapy. Monocytes and lymphocytes were
      modestly increased, while neutrophils were decreased 4 weeks after treatment.
      Lymphocyte subsets and T cell proliferative responses were not altered after
      therapy. The proportion of PBMCs capable of producing IFNgamma and TNFalpha did
      not change, while Th1 cytokine production by stimulated LPMC was decreased after
      infliximab therapy. CONCLUSION: The clinical efficacy of infliximab is based on
      local anti-inflammatory and immunomodulatory effects in the bowel mucosa, without
      generalized suppression of systemic immune functions in Crohn's disease patients.

PMID- 11284775
TI  - A 10-year survey of inflammatory bowel diseases-drug therapy, costs and adverse
      reactions.
AB  - BACKGROUND: Drug therapy for Crohn's disease and ulcerative colitis is based on
      anti-inflammatory and immunodulating drugs, nutritional support and surgical
      resection. Recently, new drugs have been introduced. AIM: To report drug
      prescriptions, costs and adverse reactions among inflammatory bowel disease
      patients in Sweden between 1988 and 1997. METHODS: Drug use was calculated from
      the national Diagnosis and therapy survey and drug costs from prescriptions and
      drug sales. Adverse drug reactions were obtained from the Medical Products
      Agency's National Pharmacovigilance system. RESULTS: The annual drug exposure for
      Crohn's disease was 0.55 million daily doses per million population, mainly
      supplementation and aminosalicylic acids. Mesalazine and olsalazine had 61%
      within this group. For ulcerative colitis patients, drug exposure was 0.61
      million daily doses per million per year and aminosalicylic acids fell from 70%
      to 65%. For inflammatory bowel disease patients, corticosteroids and nutritional
      supplementation were common. The annual average cost for inflammatory bowel
      disease drugs was 7.0 million US dollars. Annually, 32 adverse drug reactions
      were reported, mainly haematological reactions such as agranulocytosis and
      pancytopenia (60%), followed by skin reactions. Only two deaths were reported.
      Aminosalicylic acids were the most commonly reported compounds. CONCLUSIONS: Drug
      use for inflammatory bowel disease in the pre-biologic agent era rested on
      aminosalicylic acid drugs and corticosteroids with stable levels, proportions and
      costs. The level of adverse drug reactions was low but haematological reactions
      support the monitoring of inflammatory bowel disease patients.

PMID- 11284776
TI  - Population-based case control study of the safety of sulfasalazine use during
      pregnancy.
AB  - BACKGROUND: We studied the human teratogenic risk of sulfasalazine because this
      drug interferes with folate metabolism. METHODS: Case control study within the
      Hungarian Case Control Surveillance of Congenital Abnormalities, 1980-1996; based
      on 22 865 new-born infants or foetuses with congenital abnormalities, and 38 151
      babies without any detected congenital abnormalities (control group). RESULTS:
      Seventeen pregnant women (0.07%) were treated with sulfasalazine in the case
      group, and 26 (0.07%) in the control group. The overall adjusted adds ratio of
      congenital abnormalities after sulfasalazine treatment was odds ratio = 1.2 (95%
      confidence interval: 0.6-2.1). None of the analyses indicated any significant
      increased prevalence of selected congenital abnormalities among the exposed
      compared with the not exposed. CONCLUSIONS: We found no significant increased
      prevalence of selected congenital abnormalities in the children of women treated
      with sulfasalazine during pregnancy. However, the amount of information is
      limited and additional data are needed to rule out a teratogenic effect.

PMID- 11284777
TI  - Comparative efficacy of new investigational agents against Helicobacter pylori.
AB  - BACKGROUND: Emergence of antibiotic resistant Helicobacter pylori has
      necessitated the identification of alternate therapies for the treatment of this
      infection. AIM: To assess the in vitro efficacy of two investigational agents:
      DMG-MINO CL 344 (a N,N-dimethylglycylamido derivative of minocycline), and
      davercin, a cyclic carbonate of erythromycin A as compared to older antibiotics
      (clarithromcyin, azithromycin, minocycline, tetracycline, ofloxacin,
      ciprofloxacin, cefixime) against clinical isolates of H. pylori. METHODS: Testing
      was performed using the agar dilution method approved by the NCCLS subcommittee
      on antimicrobial susceptibility testing, Helicobacter pylori working group. Under
      these guidelines, Mueller-Hinton agar containing 5% aged sheep blood was used.
      All incubations were done under CampyPak Plus conditions for 72 h at 37 degrees
      C. The drug concentrations in the agar ranged from 0.016 to 16 microg/mL. Twenty
      one clarithromycin-resistant and 16 clarithromycin-susceptible clinical isolates
      of H. pylori obtained from patients with duodenal ulcer were used. H. pylori ATCC
      43504 was used as the control in all determinations. RESULTS: Against
      clarithromycin susceptible isolates, all antimicrobial agents except the
      fluoroquinolones were highly effective. Against clarithromycin-resistant H.
      pylori, the MIC50/MIC90 values showed that the tetracyclines and cefixime were
      the most efficacious agents. The fluoroquinolones and macrolides were
      ineffective. Macrolide cross-resistance was detected. CONCLUSION: Macrolide cross
      resistance prevents the use of this entire class of antimicrobials when
      clarithromycin resistance is present. Tetracyclines and cefixime are possible
      alternative agents for the treatment of H. pylori infection in these patients.

PMID- 11284779
TI  - An evaluation of invasive and non-invasive tests for the diagnosis of
      Helicobacter pylori infection in Chinese.
AB  - BACKGROUND: Different tests are available for diagnosing Helicobacter pylori
      infection. AIM: To compare the most commonly used tests either alone or in
      combination in Chinese patients with respect to routine clinical use or research
      purpose. METHODS: A total of 294 consecutive dyspeptic patients without previous
      H. pylori treatment were recruited. During upper endoscopy, biopsies were taken
      from the antrum and corpus, for a commercially available CLO-test, an in-house
      rapid urease test, culture, polymerase chain reaction and histological
      examination. Patients then received a 13C-urea breath test. The H. pylori status
      of each patient was determined by a concordance of test results. RESULTS: For
      routine clinical use, histology (antral plus corpus biopsies) had an accuracy of
      100%, whilst the rapid urease test had an accuracy of 99.7%. The 13C-urea breath
      test was equally reliable, with an accuracy of 94.5%. Combinations of two tests
      did not confer additional advantage over the most accurate single test. For
      research purposes, the accuracy of using the criteria of two positives out of
      three diagnostic tests was 100% and equivocal results were not found. CONCLUSION:
      Histology with or without a rapid urease test was highly accurate for routine
      clinical use. Alternatively, the 13C-urea breath test was an equally reliable non
      invasive test. The two positives out of three tests approach was highly reliable
      in predicting H. pylori status of untreated Chinese patients in a research
      setting.

PMID- 11284778
TI  - High prevalence of mixed infections by Helicobacter pylori in Hong Kong:
      metronidazole sensitivity and overall genotype.
AB  - BACKGROUND: Diversity in metronidazole susceptibility and genotypes of
      Helicobacter pylori have been reported with varying results in different areas.
      AIMS: To investigate the prevalence of multiple strain infection in a symptomatic
      Chinese population and to determine the metronidazole susceptibility pattern and
      genotypic characteristics of these infecting strains. METHODS: Gastric biopsies
      from antrum, body and cardia were taken during upper endoscopy in symptomatic
      patients referred to our department. Pooled cultures and single colony isolates
      were obtained and tested for metronidazole susceptibility and random amplified
      polymorphic DNA (RAPD) fingerprint patterns. RESULTS: A total of 461 isolates
      were successfully cultured from 46 patients. Fifty-seven per cent of subjects had
      metronidazole-resistant strains. Among them, 77% carried a mixture of sensitive
      and resistant strains, non-uniformly distributed in the gastric mucosa. Mixed
      genotypes were found by RAPD typing in 24% of subjects. These did not correlate
      with the metronidazole susceptibility/resistance pattern. CONCLUSION: H. pylori
      infections with mixed metronidazole sensitive/resistant strains and mixed
      genotypes are common in Hong Kong. This makes it prudent to use bacterial strains
      from several biopsy sites when testing for traits such as drug resistance or
      virulence in relation to disease.

PMID- 11284780
TI  - Nitrofurantoin quadruple therapy for Helicobacter pylori infection: effect of
      metronidazole resistance.
AB  - BACKGROUND: Antibiotic resistance has increasingly been recognized as the major
      cause of treatment failure for Helicobacter pylori infection. New therapies for
      patients with metronidazole- or clarithromycin-resistant H. pylori are needed.
      AIM: To investigate the role of nitrofurantoin quadruple therapy for the
      treatment of H. pylori. METHODS: Patients with confirmed H. pylori infection
      received nitrofurantoin (100 mg t.d.s.), omeprazole (20 mg b.d.), Pepto-Bismol
      (two tablets t.d.s.), and tetracycline (500 mg t.d.s.) for 14 days. Four or more
      weeks after the end of therapy, outcome was assessed by repeat endoscopy with
      histology and culture or urea breath testing. RESULTS: Thirty patients were
      entered, including 25 men and five women; the mean age was 54.9 years. The most
      common diagnoses were duodenal ulcer (23%) and GERD (18%). The intention-to-treat
      cure rate was 70% (95% CI: 50.6-85%). Nitrofurantoin quadruple therapy was more
      effective with metronidazole-sensitive strains (88%; 15 out of 17) than with
      metronidazole-resistant strains (33%; three out of nine; P=0.008). Two of the
      treatment failures had pre-treatment isolates susceptible to metronidazole, which
      were resistant after therapy. CONCLUSIONS: Because nitrofurantoin quadruple
      therapy performed inadequately in the presence of metronidazole resistance, we
      conclude that nitrofurantoin is unlikely to find clinical utility for the
      eradication of H. pylori.

PMID- 11284781
TI  - Maximal acid reflux control for Barrett's oesophagus: feasible and effective.
AB  - The treatment of patients with Barrett's oesophagus is controversial. Debate
      exists regarding the use and value of high dose acid suppression as the standard
      of practice. Despite prolonged use of high dose proton pump inhibitors (40 mg
      omeprazole, 60 mg lansoprazole), most studies have shown no convincing evidence
      of significant regression of Barrett's length. These studies, however, have used
      fixed doses of proton pump inhibitors and did not regularly document control of
      oesophageal acid exposure. AIM: To determine whether regression of Barrett's
      epithelium can be achieved with documented maximal acid suppression. METHODS: We
      have prospectively followed nine patients with Barrett's oesophagus (eight male;
      mean age 60 years) for more than 1 year. They were all treated using medical
      therapy with pH monitoring documenting oesophageal acid exposure over 24 h < 1.6%
      of the time, and with two or more esophagogastroduodenoscopies performed by the
      same endoscopist. RESULTS: Acid control was individually tailored and achieved
      with proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) and
      ranitidine at bedtime (HS) (Ran) if necessary. All nine patients (100%) showed
      some evidence of regression. All nine patients (100%) showed a decrease in
      Barrett's length (mean 2 cm, range 1-3 cm). Six out of nine (66.67%) patients
      showed evidence of squamous islands on the last oesophagogastroduodenoscopy. The
      mean total distal oesophageal acid exposure was 0.38% (range: 0-1.5%). The mean
      follow-up of patients was 54 months (range: 13-118 months). CONCLUSIONS:
      Consistent and individually tailored maximal acid suppression documented by pH
      metry is achievable and may result in decreased length and development of
      squamous islands in patients with Barrett's epithelium. This approach should be
      further evaluated as potentially the preferred medical treatment for these
      patients.

PMID- 11284782
TI  - A dose-ranging, placebo-controlled, randomized trial of alosetron in patients
      with functional dyspepsia.
AB  - BACKGROUND: Functional dyspepsia is characterized by upper abdominal pain or
      discomfort. AIM: To assess the benefit of the 5-HT3-receptor antagonist alosetron
      in a pilot, dose-ranging, placebo-controlled, multicentre, randomized clinical
      trial. METHODS: A total of 320 functional dyspepsia patients received placebo
      (n=81), or alosetron 0.5 mg b.d. (n=77), 1.0 mg b.d. (n=79) or 2.0 mg b.d. (n=83)
      for 12 weeks, followed by 1 week of follow-up. Primary efficacy was the 12-week
      average rate of adequate relief of upper abdominal pain or discomfort. Secondary
      endpoints assessed pain and upper gastrointestinal symptoms. RESULTS: Twelve-week
      average rates of adequate relief of pain or discomfort were 46% (95% CI: 37-54%),
      55% (95% CI: 46-63%), 55% (95% CI: 47-64%) and 47% (95% CI: 38-55%) in the
      placebo, 0.5 mg, 1.0 mg and 2.0 mg alosetron groups, respectively. Alosetron 0.5
      mg or 1.0 mg showed potential benefit over placebo for early satiety and
      postprandial fullness. Females showed greater responses compared to males.
      Patients with adequate relief had significantly (P < 0.001) greater reductions in
      severity and frequency of functional dyspepsia symptoms than those without
      adequate relief. Constipation was the most commonly reported adverse event.
      CONCLUSIONS: Alosetron showed potential benefit in relieving functional dyspepsia
      symptoms compared to placebo. Patients with adequate relief of upper abdominal
      pain or discomfort showed improvements in multiple functional dyspepsia symptoms.

PMID- 11284783
TI  - Effect of nabumetone and aspirin on colonic mucosal bleeding time.
AB  - BACKGROUND: The management of patients taking aspirin or non-steroidal anti
      inflammatory drugs (NSAIDs) who require colonoscopy remains controversial because
      of concerns over bleeding after biopsy or polypectomy. AIM: To determine whether
      patients using the NSAID nabumetone, a non-acidic prodrug with mixed activity
      against cyclooxygenase-1 (COX-1) and COX-2, exhibited prolonged mucosal bleeding
      times and how this might compare with mucosal bleeding times in patients using
      aspirin. METHODS: We assessed triplicate mucosal bleeding times in patients
      undergoing screening flexible sigmoidoscopy. We compared 90 patients who had
      taken no aspirin or NSAIDs within the previous 2 weeks, to 60 patients who had
      received nabumetone 1 g b.d. by mouth for the previous 2 weeks, and 30 patients
      who had taken 325 mg aspirin daily for the previous 2 weeks. In each case, the
      investigator performing the study was blinded to the patient's medication.
      RESULTS: Mucosal bleeding times did not differ significantly among control or
      nabumetone-using patients. However, the patients receiving aspirin exhibited
      significant prolongation. Mucosal bleeding time correlated statistically
      significantly, but weakly, with skin bleeding time. CONCLUSIONS: Nabumetone does
      not appear to prolong mucosal bleeding time after mucosal pinch biopsy, and skin
      bleeding time does not reliably screen for prolonged mucosal bleeding time.

PMID- 11284784
TI  - Relationship between lactose digestion, gastrointestinal transit time and
      symptoms in lactose malabsorbers after dairy consumption.
AB  - BACKGROUND: The relationship of symptoms with objective measurements, as well as
      some of the mechanisms involved in lactose tolerance after yoghurt consumption,
      remain unclear. METHODS: The trial had a double-blind design in which 22 lactose
      malabsorbers received 25 g daily lactose in fresh (living bacteria > 108 cfu/g)
      yoghurt or heated (< 102 cfu/g) yoghurt for 15 days, followed by a cross-over (15
      days) after a wash-out period (14 days). The lactose digestion was determined by
      the breath H2 test, the gastric emptying (GE) with a 13C-acetate breath test and
      the revealed transit time (OCTT) by 15N-lactose-ureide test. Subjects reported
      their gastrointestinal symptoms (GIS) in a validated questionnaire. RESULTS:
      Breath H2 test indicated more effective lactose digestion after fresh yoghurt
      intake. The OCTT was shorter after heated yoghurt ingestion as compared with the
      fresh. There was lower severity of GIS (P < 0.05) after fresh yoghurt intake, and
      this showed an inverse correlation with OCTT (P < 0.05). CONCLUSIONS: Delayed
      orocoecal transit time was associated with fewer gastrointestinal symptoms. The
      improved lactose digestion and tolerance of fresh yoghurt should be mainly
      attributed to the presence of living bacteria.

PMID- 11284785
TI  - Induction interferon therapy in naive patients with chronic hepatitis C:
      increased end-of-treatment virological responses but absence of long-term
      benefit.
AB  - BACKGROUND AND AIMS: The low efficacy of interferon monotherapy and data from
      viral kinetic studies led us to evaluate the efficacy of interferon administered
      daily in chronic hepatitis C. PATIENTS AND METHODS: Thirty-eight naive patients
      with chronic hepatitis C and active liver disease randomly received 3 or 5 MU IFN
      alpha daily for 1 month, followed by the same dose three times a week for 11
      months. Results were compared to a three-times-a-week scheme of 3 MU IFN-alpha
      for 1 year. RESULTS: At the end of the induction period, 27 out of 38 (71%)
      patients had cleared HCV-RNA with a significantly higher rate in the 5 MU than in
      the 3 MU group (17 out of 18 or 94% vs. 10 out of 20 or 50%, P=0.003). The end-of
      treatment virological response rate was 66% (25 out of 38) in the induction
      groups and 40% (10 out of 25) in the control group (P=0.04). Six months after
      completion of therapy, the sustained response rate dropped to 29% (11 out of 38)
      compared to 28% (7 out of 25) in the standard regimen. CONCLUSIONS: In chronic
      hepatitis C, treatment with 5 or 3 MU IFN-alpha daily during the first month of a
      standard IFN regimen leads to significantly increased end-of-treatment
      virological responses, but long-term responses are similar to those of standard
      IFN monotherapy.

PMID- 11284786
TI  - On gastric polyps, proton pump inhibitors and long-term risks.

PMID- 11284788
TI  - Nicotine-induced NO release in colitis.

PMID- 11284790
TI  - Pantoprazole and cyclosporine or tacrolimus.

PMID- 11284791
TI  - Atopy-related diseases.

PMID- 11284792
TI  - Molecular regulation of class switch recombination to IgE through epsilon
      germline transcription.

PMID- 11284793
TI  - Interactions between genes and environment in the development of asthma.

PMID- 11284794
TI  - Adult-onset asthma is associated with self-reported mold or environmental tobacco
      smoke exposures in the home.
AB  - BACKGROUND: In recent years, we have gained better knowledge about the influence
      of indoor environments on respiratory symptoms and asthma. The purpose of this
      study was to examine certain exposures in the home environment and the risk of
      adult-onset asthma. METHODS: A nested case-referent study of adult-onset asthma
      was performed in a random population sample (n = 15813), aged 20-50 years. Cases
      for the study included subjects reporting "physician-diagnosed" asthma (n= 174).
      The referents (n = 870) were randomly selected from the whole population sample.
      The case-referent sample was investigated with a comprehensive mailed
      questionnaire about exposures in the home environment, asthma, respiratory
      symptoms, smoking habits, and atopy. Odds ratios (OR) with 95% confidence
      intervals (CI) were calculated while controlling for age, sex, smoking, and
      atopy. RESULTS: Increased adjusted OR for asthma were associated with exposure to
      molds (OR 2.2, 95%, CI 1.4-3.5), environmental tobacco smoke (OR 2.4, 95%, CI 1.4
      4.1), and the presence of a wood stove (OR 1.7, 95% CI 1.2-2.5). CONCLUSIONS:
      This population-based case-referent study indicates that self-reported domestic
      exposures to molds or environmental tobacco smoke can be associated with adult
      onset asthma.

PMID- 11284795
TI  - Specific immunotherapy prevents increased levels of allergen-specific IL-4- and
      IL-13-producing cells during pollen season.
AB  - BACKGROUND: Specific allergen immunotherapy (SIT) is effective for treatment of
      IgE-mediated diseases: however, the mechanisms of action still remain unclear.
      Earlier, we showed that IL-4 and IL-13 are produced in response to specific
      allergens. The aim of this study was to investigate whether these cytokine
      responses were affected by allergen SIT, and, furthermore, to evaluate the effect
      of SIT on allergen-specific IgE and IgG4 levels. METHODS: Blood samples from
      pollen-sensitized individuals were collected before the pollen season (before
      treatment) and during the pollen season (after SIT or placebo treatment).
      Peripheral blood mononuclear cells were activated in vitro with allergens and the
      numbers of IL-4-, IL-13-, IL-10-, and IFN-gamma-producing cells were determined
      by ELISPOT. Serum levels of allergen-specific IgE and IgG4 were measured by RAST
      and ELISA, respectively. RESULTS: The numbers of IL-4- and IL-13-producing cells
      were shown to be increased in the placebo group during the pollen season, an
      increment which was absent in patients receiving allergen SIT. We found an
      increase in allergen-specific IgG4 in the SIT-treated individuals, but not in the
      placebo group. Both groups displayed elevated specific IgE levels during the
      pollen season. CONCLUSIONS: Taken together, our data show a downregulation of IL
      4- and IL-13-producing cells in peripheral blood after SIT, suggesting induction
      of nonresponsiveness/tolerance or a redistribution of these cells. Furthermore,
      we demonstrate that SIT acts on antibody production by increasing the specific
      IgG4 levels.

PMID- 11284796
TI  - Three years of specific immunotherapy with house-dust-mite extracts in patients
      with rhinitis and asthma: significant improvement of allergen-specific parameters
      and of nonspecific bronchial hyperreactivity.
AB  - Twenty-seven patients with allergy to house-dust mite and the clinical symptoms
      of perennial rhinitis and/or mild asthma were treated with specific immunotherapy
      (SIT) with standardized extracts of house-dust mite for 3 years. The success of
      therapy was evaluated in yearly intervals by 1) subjective rhinitis and asthma
      scores. 2) allergen-specific skin and conjunctival tests. 3) nonspecific
      bronchial hyperreactivity to methacholine. 4) medication scores of rhinitis and
      asthma. SIT induced a significant improvement of all parameters already after 1
      year, with further improvement in the follow-up measurements at 2 and 3 years. We
      found a constant improvement of the rhinitis and asthma symptom scores, a reduced
      reactivity in the skin prick and conjunctival provocation tests, and a constantly
      increasing reduction of bronchial hyperreactivity to methacholine. Concomitantly,
      the use of medication (topical corticosteroids, beta2-mimetics, and
      antihistamines) was reduced. Our data support the concept that SIT with
      standardized extracts of house-dust mite results in an improvement of allergen
      specific parameters in patients with perennial rhinitis and intermittent asthma.
      This beneficial effect of SIT on allergen-specific immune parameters seems to
      induce also a diminution of nonspecific bronchial hyperreactivity and enables
      reduction of symptomatic treatment.

PMID- 11284797
TI  - Exposure to pets and atopy-related diseases in the first 4 years of life.
AB  - BACKGROUND: It is still unclear how early-life exposure to pets is related to
      children's risk of developing atopy-related diseases. We estimated associations
      between early-life exposure to pets and atopy-related diseases at 0-4 years of
      life in a cohort of Norwegian children. METHODS: A population-based cohort of
      2531 children born in Oslo, Norway, was followed from birth to the age of 4
      years. Information on early-life exposure to pets, a number of possible
      confounders, and atopy-related diseases was mainly collected by questionnaire.
      RESULTS: In logistic regression analysis adjusting for potential confounders, the
      odds ratio for being exposed to pets in early life (reference category: not
      exposed) was, for bronchial obstruction at 0-2 years of life, 1.2 (95% confidence
      interval 0.9, 1.8); for asthma at the age of 4 years, 0.7 (0.5, 1.1); for
      allergic rhinitis at the age of 4 years, 0.6 (0.4, 1.0); and for atopic eczema at
      0-6 months of life, 0.7 (0.5, 0.9). CONCLUSIONS: The results indicate that early
      life exposure to pets or lifestyle factors associated with exposure to pets
      reduce the risk of developing atopy-related diseases in early childhood. However,
      these findings might also be explained by selection for keeping pets.

PMID- 11284798
TI  - Health-related quality of life assessment in young adults with seasonal allergic
      rhinitis.
AB  - BACKGROUND: In health-related quality of life (HRQL) studies on allergic
      rhinitis, both disease-specific and generic questionnaires have been extensively
      used. Seasonal allergic rhinitis (SAR) has been studied mainly by focusing on
      symptomatology. The present study aimed to evaluate the SAR-HRQL by means of two
      questionnaires, the Medical Outcome Study Short Form Health Survey (SF-36) and a
      new instrument examining satisfaction in 32 aspects of daily life: the
      Satisfaction Profile (SAT-P). METHODS: Thirty-three patients with SAR (aged
      33.5+/-8.5 years; 12 men, 21 women) were evaluated during and 2 months after the
      pollen season. Data were compared with reference samples by t-test, and baseline
      and follow-up HRQL scores were compared by a matched-pair test. RESULTS:
      Patients' HRQL scores collected during the pollen season were significantly lower
      than reference sample data in many SF-36 scores and in one SAT-P item. No
      differences emerged between SF-36 and SAT-P scores collected outside the pollen
      season and reference sample scores. Compared to baseline, outside the pollen
      season, patients reported significantly higher scores in the following SF-36
      scales: physical functioning (P=0.002), physical role (P=0.00001), bodily pain
      (P=0.01), and vitality (P=0.008); and significantly higher scores in only two SAT
      P items (physical well-being [P=0.009] and resistance to stress [P=0.01]).
      CONCLUSIONS: Our data confirm the utility of using symptomatologic and health
      status questionnaires in evaluating the HRQL of SAR patients. More general
      quality of life questionnaires may prevent the symptomatologic and functional
      problems from being adequately recognized and managed. SAT-P can be a fruitful
      additional tool in HRQL evaluation.

PMID- 11284799
TI  - Is obesity a risk factor for childhood asthma?
AB  - BACKGROUND: In adolescents and adults, an association between obesity and asthma
      was found in females. Does this sex-specific association already exist in young
      children? METHODS: Questionnaire data on 9357 5- and 6-year-old German children
      were collected in 1997 in two rural regions in Bavaria. The diagnosis of asthma,
      hay fever, and eczema was ascertained with the ISAAC core and other validated
      questions. Overweight was defined by a BMI of >90th and < or =97th percentile and
      obesity by a BMI of >97th percentile. RESULTS: The lifetime prevalence of
      doctor's diagnosed asthma in girls was 3.5% (95%, CI 2.9-4.1%) for normal weight,
      5.8% (95% CI 3.2-8.4%) for overweight, and 10.3% (95% CI 5.3-15.2%) for obesity,
      whereas no relation to weight was found in boys. Hay fever and eczema were
      unrelated to weight in girls and boys. The adjusted odds ratio for asthma in
      girls was 2.12 (95% CI 1.22-3.68) for overweight and 2.33 (95% CI 1.13-4.82) for
      obesity. CONCLUSIONS: A sex-specific association with doctor's diagnosed asthma
      was also observed in girls at school entry. Since this association was confined
      to doctor's diagnosed asthma in the absence of other atopic conditions, and no
      association with other atopic manifestations was found, we hypothesize that this
      association is related to factors other than atopic sensitization.

PMID- 11284800
TI  - Effects of in vitro treatment with fluticasone propionate on natural killer and
      lymphokine-induced killer activity in asthmatic and healthy individuals.
AB  - BACKGROUND: Topical corticosteroids are beneficial in the treatment of allergic
      respiratory disorders; they exert effects on a number of cells involved in
      allergic inflammatory reactions. On the other hand, major histocompatibility
      complex (MHC)-unrestricted cytotoxicity (i.e., natural killer [NK] cell activity)
      may play a role in the inflammatory allergic reaction. The objective was to gain
      insight into the mechanisms of the therapeutic effects of fluticasone propionate
      (FP), an inhaled corticosteroid used in asthma and rhinitis therapy. Therefore,
      we evaluated the NK and lymphokine-activated killer (LAK) activity of effector
      cells in vitro treated or not with FP. METHODS: Evaluations were made on
      peripheral blood mononuclear cells (PBMNCs), obtained from healthy volunteers (n
      = 10) and from asthmatic atopic subjects (n = 10) with allergy to Parietaria.
      RESULTS: Asthmatic patients had significantly increased NK activity (P= 0.0008),
      and interleukin (IL)-2- (P=0.0005) and interferon (IFN)-alpha-induced LAK
      activities (P=0.0005). In both groups, FP 10(-7) M significantly reduced NK
      activity (P<0.0001), IL-2-induced LAK activity (P<0.0001), and IFN-alpha-induced
      LAK activity (P<0.0001). Similar results were obtained with FP 10(-8) M.
      CONCLUSIONS: Since MHC-unrestricted cytotoxicity has been implicated in the
      development of allergen-induced eosinophilic airway inflammation, inhibition of
      NK and LAK activity by FP may contribute to the steroid therapeutic effect in
      asthma.

PMID- 11284801
TI  - Smoking and the development of allergic sensitization to aeroallergens in adults:
      a prospective population-based study. The Copenhagen Allergy Study.
AB  - BACKGROUND: Several cross-sectional population-based studies have reported a
      negative association between smoking and allergic sensitization to aeroallergens.
      In a prospective study, we investigated the association between smoking and the
      development (incidence) of allergic sensitization as reflected by skin prick test
      (SPT) positivity and specific IgE positivity. METHODS: Participants in a
      population-based study of 15 69-year-olds in 1990 were invited to a follow-up in
      1998. Thus, SPT positivity and specific IgE positivity to common aeroallergens
      were assessed in 734 subjects (participation rate: 69.0%) on two occasions 8
      years apart. The effect of smoking on the development of allergic sensitization
      was adjusted for potential confounders such as age, sex, family history of hay
      fever, educational level, and total IgE. RESULTS: During the follow-up period, 58
      and 33 subjects developed SPT positivity and specific IgE positivity,
      respectively. The risk of developing SPT positivity (adjusted odds ratio: 0.45,
      95% CI 0.21-0.98) and specific IgE positivity (adjusted odds ratio: 0.62, 95%, CI
      0.26-1.49) was lower among sustained smokers than never-smokers. CONCLUSIONS: In
      this adult population, sustained smoking was negatively associated with the
      development of allergic sensitization to aeroallergens during an 8-year follow
      up. This negative association, if real, might be due to an immunosuppressive
      effect of smoking.

PMID- 11284802
TI  - Cell and cytokine profiles in nasal secretions from patients with nasal
      polyposis: effects of topical steroids and surgical treatment.
AB  - BACKGROUND: Nasal polyposis (NP), a chronic inflammatory disease of the paranasal
      sinus mucosa, is frequently associated with asthma. Previous reports showed that
      surgical treatment for nasal polyps may influence asthma evolution. We
      hypothesized that sinus surgery may alter the cytokine network in nasal
      secretions. METHODS: We evaluated the characteristics (cells and mediators) of
      nasal lavages in nine patients with untreated NP (group A), 17 patients treated
      with topical steroids (group B), 21 patients treated by nasal surgery endonasal
      ethmoidectomy associated with topical steroids (group C), and 12 healthy subjects
      (controls). RESULTS: Percentages of both eosinophils and neutrophils were higher
      in NP patients than in controls. Percentages of eosinophils and interleukin-5 (IL
      5) level were higher in group A than in group C and controls. There was a
      positive correlation between IL-5 and eosinophils. In marked contrast, IL-8, IL
      10, and IL-1beta levels were significantly higher in group C than in groups A and
      B and controls; TNF-alpha concentration was significantly lower in group C than
      in groups A and B and controls; and there was a negative correlation between IL
      10 and TNF-alpha. The percentage of eosinophils was higher in asthmatic patients
      with NP than in nonasthmatic patients. In addition, in group C, asthmatic
      patients also had a significantly higher level of IL-10 than nonasthmatic
      patients. CONCLUSIONS: Our study demonstrates that percentages of eosinophils and
      neutrophils, and IL-5 level were increased in nasal secretions from untreated
      patients with NP. Topical steroid treatment is associated with a decrease of
      inflammatory cells and mediators. In marked contrast, nasal surgery is associated
      with marked changes, in cytokine profile in nasal secretions, that are clearly
      different from those of controls and topical steroid-treated NP patients.

PMID- 11284803
TI  - Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine-induced
      nasal response in healthy adult volunteers.
AB  - BACKGROUND: Cetirizine, an effective H1-receptor antagonist, is a racemate
      mixture of two enantiomers: levocetirizine (R enantiomer) and dextrocetirizine (S
      enantiomer). METHODS: To investigate the pharmacologic activity of the two
      enantiomers of cetirizine, we conducted a randomized, double-blind, four-way,
      crossover study to assess the effect of treatment with 5 mg levocetirizine, 5 mg
      dextrocetirizine, and 10 mg cetirizine and matched placebo, on histamine-induced
      changes in the nasal airways of 24 healthy volunteers. Four hours after a single
      oral intake, all subjects were challenged by nasal aerosol application with
      increasing doubling concentrations (from 0.25 to 32 mg/ml) of histamine in both
      nostrils. Nasal resistance was measured by passive anterior rhinomanometry (PAR),
      and changes in histamine threshold were calculated together with the absolute
      number of sneezes after each challenge. RESULTS: Both levocetirizine and
      cetirizine significantly attenuated the histamine-induced increase in nasal
      airway resistance by nearly 50% (from a median resistance of 2.51 Pa per cm3/s to
      1.29 and 1.31 Pa per cm3/s, respectively) at the maximal concentration, and they
      concomitantly increased the histamine threshold by fourfold (from 8 to 32 mg/ml),
      compared with placebo. Sneezing was also attenuated by both levocetirizine and
      cetirizine. However, these antihistaminic effects were not seen with
      dextrocetirizine. CONCLUSIONS: This study shows a similar activity of
      levocetirizine and cetirizine on the inhibition of histamine-induced increase in
      nasal resistance, indicating that the antihistaminic properties of cetirizine are
      probably attributable to levocetirizine.

PMID- 11284805
TI  - Malignancy masquerading as food hypersensitivity.

PMID- 11284804
TI  - Asthma and allergy in Russian and Norwegian schoolchildren: results from two
      questionnaire-based studies in the Kola Peninsula, Russia, and northern Norway.
AB  - BACKGROUND: Previous studies have shown that the prevalence of asthma and allergy
      in children is lower in Eastern than Western Europe. METHODS: We have compared
      the prevalence of asthma, respiratory symptoms, allergic rhinoconjunctivitis, and
      atopic dermatitis in schoolchildren aged 7-13 years in a questionnaire-based
      study conducted in the city of Nikel on the Kola Peninsula, Russia, in 1994 (n =
      1143) and another conducted in northern Norway in 1995 (n = 8676). RESULTS: The
      prevalence of diagnosed asthma was 5.1% in Russian children and 8.6% in Norwegian
      children; RR =0.58 (95% CI: 0.44-0.76). The prevalence of all respiratory
      symptoms was higher in Russian children. The prevalence of allergic
      rhinoconjunctivitis was 16.9%, in Russian children and 22.1%, in Norwegian
      children: RR =0.74 (95% CI: 0.65-0.85). The prevalence of atopic dermatitis was
      7.4% in Russian children and 19.7% in Norwegian children; RR=0.38 (95% CI: 0.31
      0.46). CONCLUSIONS: We conclude that the prevalence of diagnosed asthma, allergic
      rhinoconjunctivitis, and atopic dermatitis was higher in Norwegian than Russian
      schoolchildren. The higher prevalence of respiratory symptoms in Russian children
      probably reflects a higher prevalence of undiagnosed, nonallergic asthma.

PMID- 11284806
TI  - Millet, a potentially life-threatening allergen.

PMID- 11284807
TI  - Cockroach allergy and asthma.

PMID- 11284808
TI  - Urticaria to hydrocortisone.

PMID- 11284809
TI  - Honeymoon rhinitis.

PMID- 11284810
TI  - Systemic reactions on SPT to latex.

PMID- 11284811
TI  - Chronic urticaria to wheat.

PMID- 11284812
TI  - Anaphylaxis induced by exercise and wine.

PMID- 11284813
TI  - Continuous regional analgesia: can we afford not to use it?

PMID- 11284814
TI  - Comparison of sevoflurane-nitrous oxide anaesthesia with the conventional
      intravenous-inhalational technique using bispectral index monitoring.
AB  - Ninety-one patients were randomly allocated to one of two groups. Group A was
      induced with a single vital capacity breath of 6% (end-tidal) sevoflurane in
      nitrous oxide-oxygen (2 : 1 l.min-1), whereas group B was induced with
      intravenous fentanyl 1 microg.kg-1 + propofol 2 mg.kg-1 followed by nitrous oxide
      oxygen (2 : 1 l.min-1) and sevoflurane. Induction was considered to have been
      achieved when the bispectral index value decreased to below 70. Mean induction
      time in group A (95.2 s, 95% CI 88.5-101.9 s) was longer than group B (70.3 s,
      95% CI 66.3-74.3 s; p < 0.0001). Mild coughing was more common in group A, but
      relative hypotension was more common in group B. There was no difference in the
      emergence times. Thirty minutes after emergence, there was no difference in the
      incidence of adverse effects, with the exception of essentially mild abdominal
      pain which was more frequent in group A.

PMID- 11284815
TI  - Xenon expenditure and nitrogen accumulation in closed-circuit anaesthesia.
AB  - The high price of xenon has prevented its use in routine, clinic anaesthetic
      practice. Xenon therefore has to be delivered by closed-circuit anaesthesia. The
      accumulation of nitrogen is a significant problem within the closed circuit and
      necessitates flushing, which in turn increases gas expenditure and costs. In
      previous investigations, nitrogen concentrations between 12% and 16% have been
      reported in closed-circuit anaesthesia. In order to avoid such nitrogen
      accumulation, we denitrogenised seven pigs using a non-rebreathing system and
      connected the animals to a system primed with a xenon/oxygen mixture. In
      comparison, seven pigs were anaesthetised with xenon using a standard low-flow
      anaesthetic procedure. Anaesthesia time was 2 h. Nitrogen concentrations in the
      closed system ranged from 0.08 to 7.04% and were not significantly different from
      those observed during low-flow anaesthesia. Closed-circuit anaesthesia reduced
      the xenon expenditure 10-fold compared with low-flow anaesthesia.

PMID- 11284816
TI  - Postoperative residual block after intermediate-acting neuromuscular blocking
      drugs.
AB  - The frequency and duration of postoperative residual neuromuscular block on
      arrival of 150 patients in the recovery ward following the use of vecuronium (n =
      50), atracurium (n = 50) and rocuronium (n = 50) were recorded. Residual block
      was defined as a train-of-four ratio of <0.8. An additional group of 10 patients
      received no neuromuscular blocking drugs during anaesthesia. The incidence of
      postoperative residual neuromuscular block was 64%, 52% and 39% after the use of
      vecuronium, atracurium and rocuronium, respectively. Similar numbers of patients
      were not able to maintain a sustained head or leg lift for 5 s on arrival in the
      recovery ward. The mean [range] times to attaining a train-of-four ratio of > or
      =0.8 after arrival in the recovery ward were 9.2 [1-61], 6.9 [1-24] and 14.7 [1.5
      83] min for vecuronium, atracurium and rocuronium, respectively. None of the 10
      patients who did not receive neuromuscular blocking drugs had train-of-four
      ratios <0.8 on arrival in the recovery ward. It is concluded that a large
      proportion of patients arrive in the recovery ward with a train-of-four ratio
      <0.8, even with the use of intermediate-acting neuromuscular blocking drugs.
      Although the residual block is relatively short lasting, it may occasionally be
      prolonged, requiring close observation and monitoring of such patients in the
      recovery ward.

PMID- 11284817
TI  - Comparison of the effects of intravenous alfentanil and esmolol on the
      cardiovascular response to double-lumen endobronchial intubation.
AB  - We compared the effect of alfentanil 10 microg.kg-1 and esmolol 1.5 mg.kg-1 on
      the cardiovascular responses to laryngoscopy and double-lumen endobronchial
      intubation in two groups of 20 ASA 2-3 patients undergoing pulmonary surgery, in
      a randomised double-blind study. Arterial pressure and heart rate decreased after
      induction of anaesthesia and increased after intubation in both groups (p < 0.05)
      but remained at or below baseline values, and changes were comparable in both
      groups. Plasma catecholamine concentrations decreased after induction of
      anaesthesia in both groups (p < 0.05). Epinephrine concentrations increased in
      the esmolol group after intubation (p < 0.05) but remained below baseline in the
      alfentanil group (p < 0.05). Norepinephrine concentrations increased
      significantly in both groups after intubation but were higher in the esmolol
      group (p < 0.05). Although both esmolol 1.5 mg.kg-1 and alfentanil 10 microg.kg-1
      similarly attenuated the arterial pressure and heart rate response to
      endobronchial intubation, plasma catecholamine concentrations increased in the
      esmolol group to values greater than previously reported after tracheal
      intubation.

PMID- 11284818
TI  - Indices of nitric oxide synthesis and outcome in critically ill patients.
AB  - We measured the concentrations of serum nitrates/nitrites and plasma cyclic
      guanosine monophosphate as markers of nitric oxide synthesis in patients with or
      without septic shock for 5 days following admission to intensive care. We found
      that nitrate/nitrite concentrations, when corrected for the effect of renal
      failure, were significantly higher in patients with septic shock, both on
      admission and in the final samples drawn. In a logistic regression analysis, the
      rate of change of nitrate/nitrite concentration was associated with survival to
      day 28 (falling in survivors). The concentration of cyclic guanosine
      monophosphate when corrected for the confounding effects of renal function and
      platelet count, was only associated with the septic shock group on admission.

PMID- 11284819
TI  - Levobupivacaine.
AB  - Regional anaesthesia has seen the development of a new local anaesthetic:
      levobupivacaine. This review aims to outline the rationale underlying the
      development of levobupivacaine and to consider its place in modern regional
      anaesthesia.

PMID- 11284820
TI  - Evaluation of the disposable Vital View laryngoscope apparatus.
AB  - The Vital View laryngoscope (Vital Signs, NJ, USA) consists of a plastic
      disposable blade containing a fibrelight and a non-disposable handle; there is
      therefore no need to sterilise the blade and no concern about disintegration of
      the fibrelight. In a random cross-over design, we compared the Vital View
      laryngoscope with a conventional metal fibrelight laryngoscope (Welch Allyn, NY,
      USA) in 100 patients. The Vital View laryngoscope produced a brighter field than
      the metal laryngoscope (p < 0.001), whereas there was no significant difference
      in the view of the glottis or the success rate of tracheal intubation. In no
      patient did any problem occur, such as damage to the laryngoscope blade or loss
      of light during laryngoscopy. In another 10 patients, prevention of light
      emission from the side of the laryngoscope blade reduced the brightness (p < 0.
      01). This indicated that the brightness of the Vital View laryngoscope is
      produced by light emission not only from the tip of the blade but also from the
      side of the blade. Therefore, the disposable Vital View laryngoscope can be used
      as effectively as a conventional non-disposable laryngoscope.

PMID- 11284821
TI  - A case of extensive block with the combined spinal-epidural technique during
      labour.
AB  - The increasing use of combined spinal-epidural analgesia in obstetric practice
      has arisen from a desire to achieve a rapid onset of analgesia while reducing the
      intensity of the motor block. Although the procedure has an excellent safety
      profile, as with any technique there are potential problems. Difficulty in
      assessing the position of the epidural catheter after establishment of the spinal
      blockade may lead to an abnormally extensive block when a full-strength local
      anaesthetic solution is used. We present a case in which the use of 0.5%
      bupivacaine to top-up the epidural component of a combined spinal-epidural
      resulted in a total spinal block. The possible causes of this complication are
      discussed.

PMID- 11284822
TI  - Management of comatose head-injured patients: are we getting any better?
AB  - This re-survey of neurosurgical centres was conducted to determine whether the
      publication of management guidelines has resulted in changes in the intensive
      care management of severely head-injured patients (defined as Glasgow Coma Score
      < 9) in the UK and Ireland. Results were compared with data collected from a
      similar survey conducted 2 years earlier. Almost 75% of centres monitor
      intracranial pressure in the majority of patients and 80% now set a target
      cerebral perfusion pressure of > 70 mmHg. The use of prolonged hyperventilation
      (> 12 h) is declining and the target PaCO2 is now most commonly > 4 kPa. More
      centres maintain core temperature < 36.5 degrees C. Although wide variations in
      the management of severely head-injured patients still exist, we found evidence
      of practice changing to comply with published guidelines.

PMID- 11284823
TI  - Incidence of diaphragmatic paralysis following supraclavicular brachial plexus
      block and its effect on pulmonary function.
AB  - Thirty unpremedicated ASA physical status 1-3 patients aged between 18 and 69
      years, scheduled for upper limb surgery, received a conventional supraclavicular
      brachial plexus block using a nerve stimulator and bupivacaine 0.375% 0.5 ml.kg
      1. Spirometric measurements of pulmonary function and ultrasonographic
      assessments of diaphragmatic function were made before the block and at 10-min
      intervals after injection until full motor block of the brachial plexus had
      developed. Complete paralysis of the ipsilateral hemidiaphragm occurred in 50% of
      patients. Seventeen per cent of patients had reduced diaphragmatic movement and
      the rest (33%) had no change in diaphragmatic movement. Those with complete
      paralysis all showed significant decreases in pulmonary function, whereas those
      with reduced or normal movement had minimal change. All patients remained
      asymptomatic throughout, with normal oxygen saturation on room air.

PMID- 11284824
TI  - A comparison of the intubating and standard laryngeal mask airways for airway
      management by inexperienced personnel.
AB  - Twenty-four inexperienced participants were timed inserting the intubating
      laryngeal mask airway and the laryngeal mask airway in 75 anaesthetised subjects.
      Adequacy of ventilation was assessed on a three-point scale. The pressure at
      which a leak first developed around the device's cuff was also measured. There
      was no significant difference in insertion time or the likelihood of achieving
      adequate ventilation between devices. However, the intubating laryngeal mask
      airway was better at providing adequate ventilation without audible leak (58/75
      (77%) vs. 42/75 (56%); p = 0.009). The median (range [IQR]) pressure at which an
      audible leak developed was higher for the intubating laryngeal mask airway, 34.5
      (14-40 [29-40]) cmH2O, than for the laryngeal mask airway, 27.5 (14-40 [22-33])
      cmH2O (p < 0.001). The intubating laryngeal mask airway is worthy of further
      consideration as a tool for emergency airway management for inexperienced
      personnel.

PMID- 11284825
TI  - Effect of halothane on the cerebral circulation in young children: a hysteresis
      phenomenon.
AB  - To determine the effect of halothane on the cerebral blood flow velocity (CBFV)
      with increasing then decreasing concentrations, 11 children scheduled for minor
      surgery were studied. Anaesthesia consisted of halothane, vecuronium, nitrous
      oxide in oxygen and a caudal block. End-tidal carbon dioxide, temperature, heart
      rate and systolic arterial pressure were maintained constant. CBFV increased
      significantly between 0.5 and 1.0 MAC (p <0.001), and 0.5 and 1.5 MAC of
      halothane (p <0.001), but was not different after increasing concentration from
      1.0 to 1.5 MAC. During the decreasing phase, CBFV decreased significantly from
      1.5 to 1.0 MAC of halothane (p <0.001), whereas there was no difference in CBFV
      when decreasing halothane MAC from 1.0 to 0.5 MAC. In children, the decrease in
      CBFV during decreasing halothane concentration is not superimposable to the
      increase in CBFV seen when increasing halothane concentration, suggesting the
      presence of cerebrovascular hysteresis to halothane.

PMID- 11284826
TI  - Patient-controlled analgesia and postoperative nausea and vomiting: efficacy of a
      continuous infusion of ondansetron.
AB  - A continuous infusion of ondansetron was compared with a placebo infusion in 80
      patients undergoing major breast reconstructive surgery. All patients received a
      standard anaesthetic and a bolus dose of ondansetron after induction. They were
      then randomly allocated to receive an intravenous infusion of ondansetron or a
      placebo infusion for 24 h in a double-blind fashion. Postoperative analgesia was
      provided by patient-controlled subcutaneous diamorphine. In the ondansetron
      group, the severity of nausea, measured by a 10-point verbal rating scale, was
      reduced (p = 0.01) and fewer patients stated at postoperative interview that
      nausea and vomiting was a problem (p = 0.01).

PMID- 11284827
TI  - Opportunity knocks? - I think not.

PMID- 11284828
TI  - Problems with shared offices.

PMID- 11284829
TI  - Pre-operative assessment clinics - the last word.

PMID- 11284830
TI  - So unlikely, yet so terrifying.

PMID- 11284831
TI  - Pre-registration house officers in anaesthesia.

PMID- 11284832
TI  - Inadequate pre-operative evaluation and preparation 1.

PMID- 11284833
TI  - Inadequate pre-operative evaluation and preparation 2.

PMID- 11284834
TI  - Dentist anaesthetists.

PMID- 11284835
TI  - 'All his anxiety resolved itself into a sigh and dissolved into apathy and
      drowsiness.' - Ivan Goncharov, Russian novelist, Obolomov (1859).

PMID- 11284836
TI  - Carbon dioxide during and after the apnoea test--an illustration of the Haldane
      effect.

PMID- 11284837
TI  - Reducing unnecessary blood cross-matching.

PMID- 11284838
TI  - Universal precautions at cardiac arrests.

PMID- 11284839
TI  - The fresh-gas flow sequence at the start of low-flow anaesthesia.

PMID- 11284840
TI  - Rate of change in gas concentrations in a charged circle system with absorber.

PMID- 11284841
TI  - Training in difficult airway management.

PMID- 11284842
TI  - A complication of panendoscopy.

PMID- 11284843
TI  - A new device has to be safe and reliable too.

PMID- 11284845
TI  - A missing throat pack.

PMID- 11284846
TI  - Oxygenation during percutaneous tracheostomy.

PMID- 11284847
TI  - Improving success with the intubating laryngeal mask airway.

PMID- 11284848
TI  - Airway management/failed intubation drill.

PMID- 11284849
TI  - Placement of nasogastric tubes.

PMID- 11284850
TI  - Cocaine-excited delirium and severe acidosis.

PMID- 11284851
TI  - Lingual thyroid--another potential airway threat.

PMID- 11284852
TI  - Torticollis following induction of anaesthesia.

PMID- 11284853
TI  - Liver rupture after cardiopulmonary resuscitation during peri-operative cardiac
      arrest.

PMID- 11284854
TI  - The use of sevoflurane in acute intermittent porphyria.

PMID- 11284855
TI  - Prediction of degree of hypomagnesaemia during general anaesthesia.

PMID- 11284857
TI  - A complication of non-invasive positive pressure ventilation.

PMID- 11284858
TI  - ECG dots and regional blocks.

PMID- 11284859
TI  - A faulty PCA device.

PMID- 11284860
TI  - Pressure for success.

PMID- 11284861
TI  - Ventilator failure due to non-ISO-standard components.

PMID- 11284863
TI  - Internal jugular vein cannulation doesn't have to be a pain in the neck.

PMID- 11284864
TI  - Peri-operative peripheral nerve injury.

PMID- 11284865
TI  - Pressure sores and epidurals - blame the sheets?

PMID- 11284866
TI  - Logic in the safe practice of spinal anaesthesia - 1.

PMID- 11284867
TI  - Logic in the safe practice of spinal anaesthesia - 2.

PMID- 11284869
TI  - Prolonged epidural catheterisation - a multidisciplinary technique.

PMID- 11284870
TI  - Neuroaxial block for von Willebrand's disease.

PMID- 11284871
TI  - Identification of epidural space using air and normal saline.

PMID- 11284872
TI  - Simultaneous infusions of parenteral opioids with epidural local anaesthetics.

PMID- 11284873
TI  - Should Mendelson's syndrome be renamed?

PMID- 11284874
TI  - A disposable plastic sub-Tenon cannula.

PMID- 11284875
TI  - Useful advice when using Trilene.

PMID- 11284876
TI  - Olanzapine overdose.

PMID- 11284877
TI  - Trivial pursuit: which drug is in the syringe, nitroglycerin or epinephrine?

PMID- 11284878
TI  - Sodium citrate bottles.

PMID- 11284879
TI  - A first left-handed intravenous cannula.

PMID- 11284880
TI  - An unusual ECG!

PMID- 11284881
TI  - Dreams for the future in the field of in vivo tissue engineering.

PMID- 11284882
TI  - Tissue engineering research in oral implant surgery.
AB  - In this article, we introduce some of the more extensively evaluated technologies
      using concepts of tissue engineering. We report on hard tissue engineering and
      soft tissue engineering and their utility for dental implant therapy. For hard
      tissue engineering, we evaluated human recombinant bone morphogenetic protein-2
      and marrow mesenchymal stem cells using a model of sinus augmentation procedure
      in rabbit. We also describe distraction osteogenesis as another category for hard
      tissue engineering. In addition, we evaluate soft tissue management using
      cultured epithelial grafting for soft tissue engineering. The results of our
      tissue regeneration materials and methods in this study are positive. When the
      tissue engineering materials are used in clinics in the future, implant surgery
      could be the leading field.

PMID- 11284883
TI  - Current concepts in tissue engineering technique for repair of cartilage defect.
AB  - Hunter's observation in 1743 that cartilage "once destroyed, is not repaired,"
      has not essentially changed for 250 years. At present, there is no well
      established procedure for the repair of cartilage defect with articular
      cartilage, which has the same biochemical and biomechanical properties as the
      surrounding normal intact cartilage. In 1994, transplantation of human autologous
      chondrocytes in suspension, as reported by Brittberg et al., provided a potential
      procedure for articular cartilage repair. We have improved their procedure and
      developed a new technique which creates new cartilage-like tissue by cultivating
      autologous chondrocytes embedded in Atelocollagen gel for 3 weeks before
      transplantation. These improvements maintained the chondrocyte phenotype, evenly
      distributed chondrocytes throughout the osteochondral defects, and decreased the
      risk of leakage of grafted chondrocytes into the defects. Good clinical results
      suggest that this technique should be a promising procedure for repairing
      articular cartilage defect.

PMID- 11284884
TI  - Tissue-engineered product: allogeneic cultured dermal substitute composed of
      spongy collagen with fibroblasts.
AB  - Recently, various types of allogeneic skin substitutes including cultured
      epidermal substitute (CES), cultured dermal substitute (CDS), and cultured skin
      substitute (CSS), which are composed of keratinocytes and/or fibroblasts as the
      cellular component(s), have been used as biological wound dressings. In our
      study, the allogeneic CDS was prepared by plating fibroblasts on a spongy
      collagen. The clinical evaluation was conducted using fresh or cryopreserved
      allogeneic CDS. In 145 of our clinical cases, 95% (138/145) of various wounds
      were evaluated as achieving good or excellent results, including 96% (22/23) of
      deep dermal burns (DDB) and dermal burns (DB), 100% (53/53) of partial-thickness
      donor wounds, 91% (21/23) of traumatic skin defects, 100% (5/5) of pressure
      ulcers, 82% (9/11) of chronic skin ulcers, 100% (6/6) of coverage for debrided
      DB, and 92% (22/24) of coverage for autologous meshed graft. The results obtained
      in our study suggest that the allogeneic CDS is able to provide an effective
      therapy for patients with partial and/or full-thickness skin defects.

PMID- 11284885
TI  - Development of regenerative cardiomyocytes from mesenchymal stem cells for
      cardiovascular tissue engineering.
AB  - We have isolated a cardiomyogenic (CMG) cell line from murine bone marrow stroma.
      Stromal cells were immortalized, treated with 5-azacytidine, and spontaneous
      beating cells were repeatedly screened for. The cells showed a fibroblast-like
      morphology. However, this morphology changed after 5-azacytidine treatment in
      about 30% of the cells, which connected with adjoining cells after 1 week, formed
      myotube-like structures and began spontaneous beating after 2 weeks, and beat
      synchronously after 3 weeks. These cells expressed atrial natriuretic peptide
      (ANP) and brain natriuretic peptide (BNP). Electron microscopy revealed a
      cardiomyocyte-like ultrastructure including typical sarcomeres and atrial
      granules. They had sinus node-like or ventricular cell-like action potentials.
      Analysis of the isoform of contractile protein genes, such as myosin and alpha
      actin, indicated that their phenotype was similar to fetal ventricular
      cardiomyocytes. These cells expressed Nkx2.5, GATA4, TEF-1, and MEF2-C mRNA
      before 5-azacytidine treatment, and expressed MEF2-A and MEF2-D after treatment.
      This new cell line provides a powerful model for the study of cardiomyocyte
      transplantation.

PMID- 11284886
TI  - Hybrid artificial liver using hepatocyte organoid culture.
AB  - We developed 2 types of hybrid artificial liver modules using hepatocyte organoid
      culture. One was a polyurethane foam (PUF)/hepatocyte spheroid packed-bed module.
      Hepatocytes spontaneously formed spheroids in the PUF pores, and they maintained
      liver-specific functions well for at least 2 weeks in vitro. As a preclinical
      experiment, a hybrid artificial liver with 200 g porcine hepatocytes was applied
      to a pig (25 kg) with liver failure and showed that the hybrid artificial liver
      was effective in support of liver functions and stabilization of general
      conditions. We established a new technique of hepatocyte organoid formation using
      centrifugal force. A hepatocyte organoid formed by centrifugation in hollow
      fibers maintained functions for more than 4 months in vitro. We developed a new
      sinusoid-like structure module having hollow fibers arranged by spacers in a
      micro-regular arrangement. Inoculated hepatocytes in the extra-fiber space of the
      module formed the organoid by centrifugation, and they maintained the functions
      for at least 1 month in vitro. The results indicated that this module seems to be
      promising as a hybrid artificial liver.

PMID- 11284887
TI  - Recombinant human bone morphogenetic protein-2 potentiates the in vivo osteogenic
      ability of marrow/hydroxyapatite composites.
AB  - A composite of marrow mesenchymal stem cells (MSCs) and porous hydroxyapatite
      (HA) has bone-forming capability. To promote the capability, we added recombinant
      human bone morphogenetic protein-2 (BMP) to the composite. The bone formation was
      assessed by rat subcutaneous implantation of 4 different kinds of implants, i.e.,
      HA alone, BMP/HA composites, MSCs/HA composites, and the composites containing
      BMP (MSCs/BMP/HA). Both HA and the BMP/HA composites did not show bone formation
      at any time after implantation. The MSCs/HA composites showed moderate bone
      formation at 4 weeks and extensive bone formation at 8 weeks. The MSCs/BMP/HA
      composites showed obvious bone formation together with active osteoblasts at 2
      weeks and more bone formation at 4 and 8 weeks. The MSCs/BMP/HA composites
      demonstrated high alkaline phosphatase and osteocalcin expression at both the
      protein and gene levels. These results indicate that the combination of MSCs,
      porous HA, and BMP synergistically enhances osteogenic potential and provides a
      rational basis for their clinical application in bone reconstruction surgery.

PMID- 11284888
TI  - Evaluation of water and electrolyte transport of tubular epithelial cells under
      osmotic and hydraulic pressure for development of bioartificial tubules.
AB  - Our aim was to develop bioartificial tubules using tubular epithelial cells and
      artificial membranes and evaluate the function of water and electrolyte transport
      by various tubular epithelial cells. The cells were cultivated onto extracellular
      matrix (ProNectin F) coating polycarbonate membrane. Water transport from the
      apical to the basolateral site of cells was examined using a modified Ussing
      chamber module. Water transport under colloidal osmotic pressure on the apical
      site and hydraulic pressure on the basolateral site were higher in JTC-12, LLC
      PK1 cells than in MDCK cells. Water transport under osmotic plus hydraulic
      pressure was highest in LLC-PK1 cells. We made bioartificial tubules using LLC
      PK1 cells and polysulfone hollow fiber cartridges. Water and Na ion transport
      function was high, and BUN and creatinine passage was recognized in these
      bioartificial tubules. BUN and creatinine concentrations of reabsorption fluid in
      these bioartificial tubules were significantly lower than those concentrations of
      control media and of noncell attached polysulfone hollow fiber cartridges. Though
      LLC-PK1 cells were more preferable cells for the use of bioartificial tubules in
      terms of water and electrolyte transport, the passage of BUN and creatinine was
      not appropriate for clinical use. To select more preferable cells for
      bioartificial tubules which transport water and electrolytes and do not induce
      passage of uremic toxins is necessary.

PMID- 11284889
TI  - A honeycomb collagen carrier for cell culture as a tissue engineering scaffold.
AB  - As a three-dimensional carrier for cell culture, a honeycomb structure cell
      scaffold was created from atelopeptide collagen Types I, II, and III. The
      diameter of the honeycomb pores ranged from 100 to 1,000 microm. The depth of the
      pores was from 10 to 3,000 mm. The scaffold was elastic and hard. Creation of
      various shapes was easy, and these shapes were easily maintained. Human
      fibroblasts, CHO-K1, BHK-21, and bovine endothelial cells were cultured with the
      scaffold. The growth curves of these cells were satisfactory. These results
      suggest that this carrier is a suitable scaffold for cell culture and will be
      useful as a three-dimensional tissue engineering scaffold.

PMID- 11284890
TI  - Clinical long-term results of vascular prosthesis sealed with fragmented
      autologous adipose tissue.
AB  - Tissue engineering can improve the former limitations of artificial organs. This
      article reports the long-term clinical results of grafts constructed with
      fragmented autologous adipose tissue. We did a retrospective analysis of a series
      of 53 patients with lower leg ischemia that received 69 fragmented adipose tissue
      (FAT) grafts implantation at our institution. The mean follow-up period was 36.0
      months. After 1, 2, 3, and 5 years, the primary potency rates were 85.3, 83.3,
      73.8, and 67.7%, respectively. The lumen of occluded areas not only at
      anastomotic sites but also in areas far from the anastomotic sites was occupied
      by a thickened neointima, which had a great number of capillary blood vessels,
      elastic laminae, smooth muscle cells, fibroblasts, and collagen fibers. This type
      of intimal hyperplasia was a characteristic finding in the FAT grafts. From the
      results of this clinical trial, we conclude that the FAT grafts are acceptable as
      vascular prostheses for ischemic lower extremities. The intimal hyperplasia at
      sites far from the anastomotic lines suggested the possibility of neointima
      formation throughout the luminal surface of the grafts.

PMID- 11284891
TI  - Midterm results of stent-graft repair for thoracic aortic aneurysms: computed
      tomographic evaluation.
AB  - Midterm observation of endovascular surgery using a fabric-covered stent graft
      for thoracic aortic aneurysms is discussed with postoperative follow-up findings
      based on regularly performed thoracic computed tomography (CT). From 1996 to
      1999, 20 patients with thoracic aortic aneurysm underwent stent-graft placement
      in our hospital. One year follow-up CT results after placement were obtained for
      17 patients. The CT scans found that there were both thrombosis and size
      reduction of aneurysm in 8 patients (46%), thrombosis without size reduction in 2
      (13%), a new ulcerlike projection (ULP) in 3 (19%), persistent minor endoleakage
      in 2 (13%), a new endoleak in 1 (6%), and a recurrent endoleak from intercostal
      arteries in 1 (6%). The new ULP formation seemed to be a peculiar problem
      stemming from an intimal injury caused by edges of the stent. Therefore, we
      recently adopted a new spiral stent instead of the previous stent to avoid the
      injury. The new endoleak suggested that aneurysmal thrombosis without size
      reduction could cause the aneurysm to develop recurrent endoleaks. From these
      findings, we concluded that midterm observation of stent-graft repair for
      thoracic aortic aneurysms did not give satisfactory results. In order to improve
      the results of endovascular surgery using stent-grafts, we need to develop safer
      stent grafts with a reliable design to prevent endoleaks and to avoid intimal
      injury of the aorta. We also hope to develop effective technologies that can
      accelerate organization of thrombus in the aortic aneurysm after stent-graft
      placement.

PMID- 11284892
TI  - Introduction of tissue engineering concepts into the field of endovascular
      grafts: an attempt to solve endoleakage problems of endovascular grafts implanted
      in aortic aneurysms.
AB  - To solve endoleakage problems of endovascular prostheses inserted in aortic
      aneurysms, a concept originating from tissue engineering was proposed. We
      proposed that in order to accelerate the thrombus inside the aneurysm, three
      major factors for successful tissue engineering, i.e., appropriate cells,
      extracellular matrices, and growth factors, should be introduced into a space
      between the endovascular grafts and the aneurysm. As a simulation model in
      animals, two kinds of fabric vascular prostheses were used. One was a small graft
      used as an endovascular graft and another was a large graft as an envelope for
      the small graft, used as the aneurysm wall. Adipose tissue fragments with fresh
      blood coagula were injected between the two grafts. The control was a preparation
      without tissue fragments. Two months and a half after surgery, the test group
      showed complete connective tissue formation in the space between the two grafts,
      but in the control, brownish thrombus remained. From this experiment, we
      speculated that tissue fragment transplantation will accelerate connective tissue
      formation of the thrombus, and this complete organization of the thrombus might
      reduce endoleakage.

PMID- 11284893
TI  - Psychiatry has much to offer for chronic pain.
AB  - OBJECTIVE: The objective of this study was to make an argument in favour of the
      inclusion of psychiatrists on chronic pain clinic teams. METHOD: The argument
      takes the form of answers to four central questions: (i) does pain involve an
      emotional experience; (ii) do psychiatric disorders accompany chronic pain; (iii)
      can psychiatric disorders present as chronic pain; and (iv) which patients
      present to pain units, and what do we know of their personalities? RESULTS: The
      affirmative case was substantiated in respect of the first three questions. In
      examining the last question, evidence indicates that patients who present to
      chronic pain units frequently have personality features that make assessment and
      therapy difficult. CONCLUSIONS: Psychiatry is the field of medicine where
      practitioners have the most experience with emotional states and personality, and
      is the only field where they have specialized skills in the diagnosis and
      treatment of psychiatric disorders. Psychiatry has much to offer in chronic pain
      management and chronic pain management teams should include a psychiatrist. This
      conclusion has resourcing and training implications.

PMID- 11284894
TI  - The human costs to staff from closure of a general hospital: an example of the
      effects of the threat of unemployment and fragmentation of a valued work
      structure.
AB  - OBJECTIVES: To describe the stressors and stress responses in medical (and to
      some extent other) staff as a result of the process of closure of a major general
      hospital. This is the first such clinical description in the literature. METHOD:
      Semistructured individual interviews were conducted with 50 senior medical staff
      and with administrators at a time of imminent closure of the hospital.
      Information was also pooled from medical unit and other hospital meetings.
      Impressions regarding the effects on other staff were also noted. RESULTS: The
      perceived threat of loss of work, meaninglessness of the closure and erosion of
      medical values caused manifestations of demoralization and stress, as well as
      overt medical symptoms and illnesses. Methods of coping included denial and other
      defences. Treatment included stress counselling at individual and group levels,
      which provided staff relief through being able to verbalize, label and connect
      their feelings and distress to valid stressors. However, the overall impact of
      counselling was limited. CONCLUSIONS: There must be an understanding of the human
      costs on staff and patients when hospital closures are contemplated.

PMID- 11284895
TI  - Patterns of critical incidents and their effect on outcome in an adolescent
      inpatient service.
AB  - OBJECTIVES: To identify patterns in critical incidents at an inpatient adolescent
      unit, to determine differences among patients who engage in critical incidents
      and those who do not, and to ascertain if there is an association between
      involvement in incidents and outcome of treatment. METHOD: Retrospective review
      of all critical incidents reported at an adolescent unit over 30 months. RESULTS:
      Of 243 adolescents consecutively admitted, 100 (41%) were involved in critical
      incidents. Aggressive acts were more common in male adolescents, among patients
      with conduct or oppositional disorder and/or in those with specific learning
      disorders, and occurred throughout the day. Self-destructive events were more
      common in female adolescents and among patients with borderline personality
      disorder, and took place mainly in the evening. Adolescents involved in critical
      incidents tended to have longer admissions and had a worse outcome, irrespective
      of other factors. CONCLUSIONS: Critical incidents are common among hospitalized
      adolescents and result in a poorer outcome. Increased structure during the
      evenings, problem-solving and social skills programmes for patients, and specific
      training for staff regarding management and minimization of critical incidents
      should be provided.

PMID- 11284896
TI  - A pessimistic attitude towards the future and low psychosocial functioning
      predict psychiatric diagnosis among treatment-seeking adolescents.
AB  - OBJECTIVE: The objective was to study factors associated with psychiatric
      diagnosis among adolescents (n = 164) seeking psychiatric care for mental
      symptoms. METHOD: Psychiatric diagnosis was confirmed by a structured diagnostic
      interview. Psychosocial functioning was assessed with the Global Assessment of
      Functioning Scale, and the Beck Depression Inventory and Offer Self-Image
      Questionnaire were also used. Background data were gathered. RESULTS: A majority
      (76%) of the adolescents met DSM-III-R criteria for psychiatric diagnosis. The
      self-image was more negative and the Beck score was higher among these
      adolescents than the others. All who had attempted suicide had a psychiatric
      disorder. Those diagnosed as having a psychiatric disorder consumed alcohol in
      order to get drunk more often than others. Continual conflicts with parents and
      smoking were not associated with the existence of a psychiatric disorder. In
      logistic regression analysis, low psychosocial functioning (OR = 3.9) and an
      uncertain or pessimistic attitude towards the future (OR = 9.1) proved to be
      independent risk factors for psychiatric disorders. CONCLUSIONS: Health service
      staff should be aware of factors associated with psychiatric disorders in
      adolescents so that they can identify those at high risk.

PMID- 11284897
TI  - Prevalence of psychiatric disorders in New Zealand prisons: a national study.
AB  - OBJECTIVE: The paper describes the methodologies and results obtained on a large
      cohort of prison inmates in New Zealand who were screened for psychiatric
      disorder. METHOD: All women and remanded male inmates in New Zealand prisons, and
      a randomly selected cohort of 18% of sentenced male inmates were interviewed.
      Interviewers used the Composite International Diagnostic Interview - Automated to
      establish DSM-IV diagnoses, and the Personality Disorders Questionnaire to
      identify personality disorder. All prisons in New Zealand were visited. RESULTS:
      The results indicate markedly elevated prevalence rates for major mental disorder
      in the prison population when compared with community samples. This is especially
      the case for substance misuse, psychotic disorders, major depression, bipolar
      disorder, obsessive- compulsive disorder and posttraumatic stress disorder. Of
      particular concern is not only the increased prevalence rates for schizophrenia
      and related disorders but also the high level of comorbidity with substance
      misuse disorders demonstrated by this group. While 80.8% of inmates diagnosed
      with bipolar disorder were receiving psychiatric treatment in the prison, only
      46.4% of depressed inmates and 37% of those suffering from psychosis were
      receiving treatment. Maori inmates were grossly overrepresented in the remand,
      female and male sentenced inmate population compared with the general population.
      CONCLUSIONS: A significant increase in provision of mental health services is
      required to cope with the high number of mentally ill inmates. The level of need
      demonstrated by this study requires a level of service provision that is quite
      beyond the capacity of current forensic psychiatry services, Department of
      Corrections Psychological Services or the prison nursing and medical officers.
      The elevated rates of common mental disorders argues for the use of improved
      psychiatric screening instruments, improved assessment and treatment capacities
      in the prison and an increased number of forensic psychiatric inpatient
      facilities to care for those psychotic inmates who are too unwell to be treated
      in the prison.

PMID- 11284898
TI  - Access to Australian mental health care by people from non-English-speaking
      backgrounds.
AB  - OBJECTIVE: This study aimed to examine access to mental health care for people
      from non-English-speaking backgrounds relative to that of people from English
      speaking backgrounds, in the context of the mental health status of both groups;
      and to consider whether, if they perceive that they have needs for care, these
      needs are met. METHOD: The study used data from the population-based Australian
      National Survey of Mental Health and Wellbeing, conducted in 1997. RESULTS:
      People from non-English-speaking backgrounds and English-speaking backgrounds
      were equally likely to experience anxiety disorders and affective disorders, but
      the former were less likely to experience substance-use disorders and any mental
      disorder. When those with each disorder type were considered alone, people from
      non-English-speaking backgrounds and English-speaking backgrounds were equally
      likely to use services for mental health problems. When those with perceived
      needs for care were considered in isolation, there was no difference between
      birthplace groups in terms of their likelihood of reporting that their needs were
      fully met. CONCLUSIONS: The study had several limitations (i.e. lack of detail on
      specific ethnic groups and exclusion of potential respondents who could not speak
      English), which mean that these findings should be interpreted with caution.
      There is a need to build on this population-based work, by oversampling people
      from particular non-English speaking communities and ensuring that those who do
      not speak English are included in population samples. Such work will further
      clarify the relative ability of people from non-English-speaking backgrounds to
      access services, and the extent to which their needs are met.

PMID- 11284899
TI  - Predictors of types of help provided to people using services for mental health
      problems: an analysis of the Australian National Survey of Mental Health and
      Wellbeing.
AB  - OBJECTIVE: Using the 1997 National Survey of Mental Health and Wellbeing, this
      study examined the types of mental health help provided to those Australians who
      use mental health services. We also sought to identify the extent to which
      sociodemographic factors, patterns of psychiatric morbidity and type of health
      practitioner seen were associated with receiving different types of mental health
      help. METHOD: Multiple logistic regressions were undertaken to identify predictor
      variables associated with receiving information, medication, psychological
      therapy, practical help and help looking after oneself or one's home. A total of
      25 predictor variables provided in the National Survey were considered including
      age, sex, marital status, labour force status, geographical location, education,
      psychological symptoms, neuroticism, diagnoses of affective, anxiety and
      substance-abuse disorders and self-identified depression, anxiety and substance
      abuse. The type of practitioner seen for mental health reasons was also
      considered. RESULTS: Of the sociodemographic factors, age was the most
      consistently associated with receiving particular types of help. Younger
      respondents were more likely to have received information whereas older patients
      reported receiving more medication. As might be expected, the type and severity
      of psychiatric morbidity and the category of health professional seen were also
      associated with receiving particular types of mental health help. CONCLUSIONS:
      There are relatively few predictor variables that suggest possible bias in the
      types of help provided. Age group of recipient is an important exception. Our
      findings suggest that older recipients of mental health care are not provided the
      range of mental health treatments offered younger people who present with similar
      problems.

PMID- 11284900
TI  - Uses of Community Treatment Orders in New Zealand: early findings.
AB  - OBJECTIVE: To assess the uses of Community Treatment Orders (CommTOs) in New
      Zealand. METHOD: A retrospective study of patients' records held by the regional
      administrator of mental health legislation and a survey of psychiatrists
      attending a conference in Dunedin. RESULTS: Males under Community Treatment
      Orders (CommTOs) outnumbered females 6:4; a high proportion were considered to
      have a major psychotic disorder; and one fifth remained under a CommTO for more
      than a year without inpatient care. Among the psychiatrists, there was a high
      level of agreement that, when used appropriately, the benefits of CommTOs
      outweigh their coercive impact on the patients; the most strongly supported
      indicator for use was the promotion of compliance with medication. The rate of
      use of CommTOs in Otago is remarkably similar to the rate in Victoria, Australia.
      CONCLUSIONS: Records suggest that a significant proportion of patients under
      CommTOs are not soon readmitted; and many clinicians in New Zealand consider
      CommTOs to be a useful strategy for managing the community care of long-term
      patients with schizophrenia and major affective disorders.

PMID- 11284901
TI  - Cardiovascular risk factors for people with mental illness.
AB  - OBJECTIVE: The objective of this study was to document the prevalence of risk
      factors for cardiovascular disease among people with chronic mental illness.
      METHOD: A cross-sectional survey was conducted of 234 outpatients attending a
      community mental health clinic in the North-western Health Care Network in
      Melbourne, Australia. Prevalence of smoking, alcohol consumption, body mass
      index, hypertension, salt intake, exercise and history of hypercholesterolemia
      was assessed. RESULTS: Compared with a community sample, the mentally ill had a
      higher prevalence of smoking, overweight and obesity, lack of moderate exercise,
      harmful levels of alcohol consumption and salt intake. No differences were found
      on hypertension. Men, but not women, with mental illness were less likely to
      undertake cholesterol screening. CONCLUSIONS: Psychiatric outpatients have a high
      prevalence of cardiovascular risk factors which may account for the higher rate
      of cardiovascular mortality among the mentally ill. Further research is needed to
      trial and evaluate interventions to effectively modify risk factors in this
      vulnerable population.

PMID- 11284902
TI  - Risk factors for HIV/AIDS and hepatitis C among the chronic mentally ill.
AB  - OBJECTIVE: The objective of this study was to document the prevalence of risk
      factors for HIV/AIDS and hepatitis C among people with chronic mental illness
      treated in a community setting. METHOD: 234 patients attending four community
      mental health clinics in the North-western Health Care Network in Melbourne,
      Australia, completed an interviewer-administered questionnaire which covered
      demographics, risk behaviour and psychiatric diagnosis. RESULTS: The sample was
      58% male, and 79% of the sample had a primary diagnosis of schizophrenia. Forty
      three per cent of mentally ill men and 51% of mentally ill women in the survey
      had been sexually active in the 12 months preceding the survey. One-fifth of
      mentally ill men and 57% of mentally ill women who had sex with casual partners
      never used condoms. People with mental illness were eight times more likely than
      the general population to have ever injected illicit drugs and the mentally ill
      had a lifetime prevalence of sharing needles of 7.4%. CONCLUSIONS: The prevalence
      of risk behaviours among the study group indicate that people with chronic mental
      illness should be regarded as a high-risk group for HIV/AIDS and hepatitis C. It
      is essential that adequate resources and strategies are targeted to the mentally
      ill as they are for other high-risk groups.

PMID- 11284903
TI  - Depressogenic cognitive schemas: enduring beliefs or mood state artefacts?
AB  - OBJECTIVE: The objective of this study was to review findings from a previously
      posited 'lock and key' hypothesis which challenge a number of assumptions about
      cognitive theories of depression. METHOD: A review of existing cognitive
      vulnerability theories is presented. Two recent studies employed to test the lock
      and key hypothesis are summarized. The hypothesis is reviewed in light of other
      diathesis-stress models of cognitive vulnerability. RESULTS: The identification
      of a depressed individual's core beliefs or cognitive schemas is a difficult
      task, with perhaps unresolvable difficulties in disentangling any mood state
      determinant. Longitudinal assessment of originally euthymic subjects appears the
      best method to investigate any cognitive risk to depression and the significance
      of diathesis-stress models. CONCLUSIONS: Empirical evidence for or against the
      validity of cognitive vulnerability theories is largely dependent upon the
      methodologies used to detect cognitive styles, as well as the nature of the
      subject groups studied.

PMID- 11284904
TI  - Family history of schizophrenia and the relationship of stress to symptoms:
      preliminary findings.
AB  - OBJECTIVE: It has been hypothesized that patients with a diagnosis of
      schizophrenia who have a positive family history for schizophrenia will show
      greater reactivity of their symptoms to increasing levels of stress or negative
      affect than will patients without such a family history. In the past this
      hypothesis has only been tested through manipulations of negative affect in
      laboratory settings. In this paper we test this hypothesis using longitudinal
      clinical data. METHOD: Data were derived from an earlier longitudinal study using
      monthly assessments of daily stressors (Hassles Scale) and symptom measures (the
      Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of
      Negative Symptoms). We compared longitudinal stress to symptom relations in 12
      patients with schizophrenia for whom a positive family history of schizophrenia
      could be identified with 12 matched schizophrenic patients without any known
      family history of psychiatric illness. RESULTS: There was evidence that patients
      with a family history of schizophrenia demonstrated a stronger relation between
      stress and total score on the Scale for the Assessment of Positive Symptoms. This
      difference appears to have primarily reflected a greater reactivity to stress of
      reality distortion symptoms in the positive family history group. The two groups
      did not differ in apparent reactivity to stress of the disorganization and
      psychomotor poverty dimensions of symptomatology. CONCLUSIONS: The results of
      this study provide support from a naturalistic, longitudinal clinical study for
      the hypothesis that reactivity to stress of some symptoms of schizophrenia may
      vary as a function of family history of the disorder.

PMID- 11284905
TI  - A comparison of the Composite International Diagnostic Interview (CIDI-Auto) with
      clinical assessment in diagnosing mood and anxiety disorders.
AB  - OBJECTIVE: Increasingly, epidemiological studies are employing computerized and
      highly standardized interviews, such as the Composite International Diagnostic
      Interview (CIDI-Auto), to assess the prevalence of psychiatric illness. Recent
      studies conducted in specialist units have reported poor agreement between
      experienced clinicians' and CIDI-Auto diagnoses. In this study we investigated
      the concordance rate between clinicians and the CIDI-Auto for the diagnosis of
      six anxiety disorders and two mood disorders, whereby the CIDI-Auto was treated
      as the 'gold standard'. METHOD: Subjects were 262 patients who were assessed by a
      clinical psychologist or psychiatrist and completed the CIDI-Auto at a tertiary
      referral unit for anxiety and mood disorders. Agreement between the clinicians'
      diagnoses and the diagnoses generated by the CIDI-Auto according to both DSM-IV
      and ICD-10 codes, were examined by kappa statistics. Sensitivity and specificity
      values were also calculated. RESULTS: Agreement between clinicians and the CIDI
      Auto (DSM-IV) ranged from poor for social phobia and posttraumatic stress
      disorder (kappa < 0.30) to moderate for obsessive- compulsive disorder (OCD;
      kappa = 0.52). Agreement between clinicians and the CIDI-Auto (ICD-10) ranged
      from poor for major depressive episode (kappa = 0.25) to moderate for OCD (kappa
      = 0.57). With the CIDI diagnosis treated as the gold standard, clinicians'
      diagnoses showed low sensitivity (kappa < 0.70) for all the disorders except for
      OCD (for ICD-10), but high specificity (kappa > 0.70) for all the disorders.
      CONCLUSION: Poor agreements between experienced clinicians and the CIDI-Auto were
      reported for anxiety and mood disorders in the current study. A major implication
      is that if diagnosis alone directed treatment, then patients could receive
      different treatments, depending on whether the computer, or a clinician, made the
      diagnosis.

PMID- 11284906
TI  - The validity of the 12-item General Health Questionnaire in Australia: a
      comparison between three scoring methods.
AB  - OBJECTIVE: To investigate the specificity and sensitivity of three different
      scoring methods of the 12-item General Health Questionnaire (GHQ-12) and hence to
      determine the best GHQ-12 threshold score for the detection of mental illness in
      community settings in Australia. METHOD: Secondary data analysis of the 1997
      Australian National Survey of Health and Wellbeing (n = 10 641), using the
      Composite International Diagnostic Interview as the gold standard for diagnosis
      of mental illness. RESULTS: The area under the Receiver Operating Characteristic
      (ROC) curve for the C-GHQ scoring method was 0.84 (95% CI = 0.83-0.86) compared
      with the area for the standard scoring method of 0.78 (95% CI = 0.76-0.80). The
      best threshold with C-GHQ was 3/4, with sensitivity 82.9% (95% CI = 80.2-85.5%)
      and specificity 69.0% (95% CI = 68.6-69.4%). The best threshold score with the
      standard scoring method was 0/1, with sensitivity 75.4% (95% CI = 72.5-78.4%) and
      specificity 69.9% (95% CI = 69.5-70.3%). These were also the best thresholds for
      a subsample of the population who had consulted a health practitioner in the
      previous 4 weeks. CONCLUSION: In the Australian setting, the C-GHQ scoring method
      is preferable to the standard method of scoring the GHQ-12. In Australia the GHQ
      12 appears to be a less useful instrument for detecting mental illness than in
      many other countries.

PMID- 11284907
TI  - A 12-month follow up of the implementation of clinical indicators in a
      consultation-liaison service.
AB  - OBJECTIVES: This paper reviews the use of clinical indicators in a consultation
      liaison (C-L) service over a 12-month period at the Royal Melbourne Hospital,
      Melbourne, Australia. METHOD: Clinical indicators and C-L data were collected
      during the 1999 calendar year. A review of the process was conducted during and
      after completion of the 12-month period. RESULTS: The system was found to be
      practical and useful. The use of clinical indicators led to the identification of
      problems and stimulated effective interventions. The use of the clinical
      indicators was associated with improvement in communication between C-L staff,
      parent units and practitioners providing follow-up. CONCLUSIONS: The
      implementation of a database and clinical indicators was a useful addition to the
      C-L service. The use of clinical indicators was effective in improving clinical
      performance. These benefits need to be balanced against increased administrative
      burden.

PMID- 11284908
TI  - The humble case report.
AB  - OBJECTIVE: There is negligible systematic information about case reports in the
      psychiatric literature. We aimed to describe case report articles published in
      the Australian and New Zealand Journal of Psychiatry (ANZJP), to provide data
      about the quality of evidence they offer, to ascertain changes over time and to
      make recommendations, based on our findings, about these articles. METHOD: All
      articles describing cases which appeared in the ANZJP between 1967 and 1999 were
      identified and examined. RESULTS: 256 articles describing a total of 479 cases
      were published over the study period. Fifty-five per cent of articles reported an
      unusual presentation. Thirty-eight per cent of cases had a mood disorder and 24%
      had a psychosis. Seventy-six per cent of patients had a positive outcome. Cases
      published in 1989-1999 were more likely to describe pharmacological treatments
      than cases published earlier. CONCLUSIONS: Clinical descriptions that lead to
      progress are undervalued. Case reports should retain a place in the ANZJP,
      provided they convey information that is new and useful (e.g. suggesting or
      refuting hypotheses) rather than simply document current practice or describe the
      unusual. Issues of patient consent and anonymity also warrant consideration.

PMID- 11284909
TI  - Anorexia nervosa in an elderly woman.
AB  - OBJECTIVE: To demonstrate a case of anorexia nervosa in the elderly and to
      highlight the need for broadening of current diagnostic criteria. CLINICAL
      PICTURE: First onset of anorexia nervosa in a 72-year-old woman following
      bereavement of her husband. TREATMENT: Nine treatments of electroconvulsive
      therapy. OUTCOME: Treatment resulted in remission of the depressive symptoms and
      improvement of eating behaviour. CONCLUSIONS: Anorexia nervosa does occur in the
      elderly and can be difficult to detect. Where comorbid depression exists it
      requires aggressive treatment.

PMID- 11284910
TI  - Clozapine rechallenge after myocarditis.

PMID- 11284911
TI  - Weight gain with antipsychotic medication.

PMID- 11284912
TI  - Neuroleptic malignant syndrome precipitated by promethazine and lorazepam.

PMID- 11284913
TI  - A dose-response relationship of imitational suicides with newspaper distribution.

PMID- 11284914
TI  - Improvement in chronic pain with transcranial magnetic stimulation.

PMID- 11284915
TI  - p53 functional assays: detecting p53 mutations in both the germline and in
      sporadic tumours.
AB  - The tumour suppressor gene p53 is the gene most often reported to be mutated in
      clinical cancers with something like half of all tumours harbouring mutations.
      Further, many studies have suggested that p53 mutations have prognostic
      importance and sometimes are a significant factor in determining the response of
      tumours to therapy. The value of knowing the p53 status of individual tumours
      will increase if currently researched strategies aimed at developing p53-based
      treatment protocols come to fruition. There are quite a number of techniques used
      to detect p53 defects in both tumours and in the germline of cancer-prone
      families, although some of these methods are indirect and each has certain
      drawbacks. In this brief review we will discuss the value of two assays of p53
      function as a means of detecting and partly characterizing p53 mutations. The two
      assays are the apoptotic assay, which measures the response of peripheral blood
      lymphocytes to radiation-induced DNA damage and the FASAY, a yeast based assay
      which assesses the ability of a given p53 protein to transactivate p53 target
      genes. Both of these assays are rapid, yielding results within 5 days. Further,
      they not only offer the possibility of detecting p53 mutations but also of
      characterizing a given mutation in terms of two of p53's most important
      functions, namely the induction of apoptosis and the transactivation of target
      genes.

PMID- 11284916
TI  - SERCA activity is required for timely progression through G1/S.
AB  - Changes in intracellular Ca2+ correlate with specific events in the cell cycle.
      Here we investigated the role of Ca2+ in the G1 phase. HEK 293 cells were
      arrested in mitosis and subjected to short-term treatments that alter Ca2+
      homeostasis prior to their release into G1. Treatment with thapsigargin (TG), an
      irreversible inhibitor of the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA)
      lengthened the G1 phase. Moreover, TG treatment also resulted in a dramatic
      alteration in cellular morphology and attachment and in the reduction of MAPK
      activity and lower levels of cyclin D1 and cyclin E proteins. Treatments with
      reagents that transiently increase or decrease cytosolic Ca2+ or that temporarily
      inactivate SERCA did not alter any of the above parameters. Cells expressing a TG
      resistant form of SERCA progressed normally through the G1/S transition after TG
      treatment. These results suggest that long-term SERCA inactivation affects cell
      cycle-dependent events and compromises progression through G1/S.

PMID- 11284917
TI  - Sensitivity of human glioma U-373MG cells to radiation and the protein kinase C
      inhibitor, calphostin C.
AB  - We assessed the radiosensitivity of the grade III human glioma cell line U-373MG
      by investigating the effects of radiation and the specific protein kinase C
      inhibitor, calphostin C on the cell cycle and cell proliferation. Irradiated
      glioma U-373MG cells progressed through G1-S and underwent an arrest in G2-M
      phase. The radiosensitivity of U-373MG cells to graded doses of either photons or
      electrons was determine by microculture tetrazolium assay. The data was fitted to
      the linear-quadratic model. The proliferation curves demonstrated that U-373MG
      cells appear to be highly radiation resistant since 8 Gy was required to achieve
      50% cell mortality. Compared to radiation alone, exposure to calphostin C (250
      nM) 1 h prior to radiation decreased the proliferation of U-373MG by 76% and
      calphostin C provoked a weakly synergistic effect in concert with radiation.
      Depending on the time of application following radiation, calphostin C produced
      an additive or less than additive effect on cell proliferation. We postulate that
      the enhanced radiosensitivity observed when cells are exposed to calphostin C
      prior to radiation may be due to direct or indirect inhibition of protein kinase
      C isozymes required for cell cycle progression.

PMID- 11284918
TI  - The geometry of proliferating dicot cells.
AB  - The distributions of cell size and cell cycle duration were studied in two
      dimensional expanding plant tissues. Plastic imprints of the leaf epidermis of
      three dicot plants, jade (Crassula argentae), impatiens (Impatiens wallerana),
      and the common begonia (Begonia semperflorens) were made and cell outlines
      analysed. The average, standard deviation and coefficient of variance (CV = 100 x
      standard deviation/average) of cell size were determined with the CV of mother
      cells less than the CV for daughter cells and both are less than that for all
      cells. An equation was devised as a simple description of the probability
      distribution of sizes for all cells of a tissue. Cell cycle durations as measured
      in arbitrary time units were determined by reconstructing the initial and final
      sizes of cells and they collectively give the expected asymmetric bell-shaped
      probability distribution. Given the features of unequal cell division (an average
      of 11.6% difference in size of daughter cells) and the size variation of dividing
      cells, it appears that the range of cell size is more critically regulated than
      the size of a cell at any particular time.

PMID- 11284919
TI  - Heterogeneity in nuclear transport does not affect the timing of DNA synthesis in
      quiescent mammalian nuclei induced to replicate in Xenopus egg extracts.
AB  - Intact G0 nuclei from quiescent mammalian cells initiate DNA synthesis
      asynchronously in Xenopus egg extracts, despite exposure to the same
      concentration of replication factors. This indicates that individual nuclei
      differ in their ability to respond to the inducers of DNA replication. Since the
      induction of DNA synthesis requires the accumulation of replication factors by
      active nuclear transport, any variation in the rate of transport among nuclei
      could contribute to the variability of DNA replication. Using the naturally
      fluorescent protein allophycocyanin (APC) coupled with the nuclear localization
      sequence (NLS) of SV40 T antigen, as a marker of nuclear uptake, we show here
      that individual G0 nuclei differ in their rate of transport over a range of more
      than 20-fold. Surprisingly, this variation has no direct influence on the timing
      or extent of DNA synthesis. Similar results were obtained by monitoring the
      uptake of nucleoplasmin, a nuclear protein present at high levels in egg
      extracts. These experiments show that the initiation of DNA synthesis is not
      driven merely by the accumulation of replication factors to some threshold
      concentration. Instead, some other explanation is needed to account for the
      timing of initiation.

PMID- 11284920
TI  - The diagnostic significance of relative bradycardia in infectious disease.

PMID- 11284921
TI  - PCR-based DNA fingerprinting (REP-PCR, AP-PCR) and pulsed-field gel
      electrophoresis characterization of a nosocomial outbreak caused by imipenem- and
      meropenem-resistant Acinetobacter baumannii.
AB  - OBJECTIVE: To demonstrate the usefulness of REP-PCR and AP-PCR on molecular
      typing of A. baumannii isolates. METHOD: From February to November 1997, 29
      inpatients at Ramon y Cajal Hospital, Madrid-23 in five intensive care units
      (ICUs) and six at two different medical departments-were either colonized or
      infected with imipenem- and meropenem-resistant Acinetobacter baumannii (IMRAB)
      strains (MICs of 64-256 mg/L). A wide antibiotic multiresistance profile was
      observed with IMRAB strains, and only tobramycin, sulbactam and colistin
      displayed valuable activity. For typing IMRAB isolates, repetitive extragenic
      palindromic sequence-based polymerase chain reaction (REP-PCR) and arbitrary
      primer sequence-based polymerase chain reaction (AP-PCR) methods were used and
      compared with pulsed-field gel electrophoresis (PFGE) as reference technique. For
      comparative purposes, 30 imipenem- and meropenem-susceptible A. baumannii (IMSAB)
      strains isolated before, during and after the outbreak were included in this
      study. RESULTS: The molecular typing results showed that the outbreak was caused
      by a single IMRAB strain (genotype 1). On the other hand, seven different
      genotypes were observed in the pre-, at- and post-outbreak strains tested by REP
      PCR. Regarding AP-PCR, three of four at-outbreak IMSAB strains were
      indistinguishable from the IMRAB profile. Thus, with AP-PCR, only six genotypes
      were obtained, apart from the IMRAB genotype. CONCLUSION: Under our experimental
      conditions, REP-PCR had a higher discriminatory power than AP-PCR, with PFGE as
      reference technique. The REP-PCR technique is a useful and expeditious method for
      the epidemiologic characterization of A. baumannii nosocomial outbreaks, the
      results being comparable to those obtained with the PFGE technique.

PMID- 11284922
TI  - Extra-laryngeal head and neck tuberculosis.
AB  - OBJECTIVE: Extra-laryngeal head and neck tuberculosis is exceptional. Therefore,
      a retrospective multicenter study in patients with head and neck tuberculosis,
      excluding solitary lymphadenitis and laryngeal locations was carried out.
      METHODS: We reviewed the patients with these features and tuberculosis
      confirmation by culture and/or histologic granuloma with presence of acid-fast
      bacilli (AFB). RESULTS: We found 16 patients with the following locations: eight
      in oral cavity and/or pharynx, four in ear, two in salivary glands, one in nose
      and one in frontal sinuses. The average duration of symptoms was 11.5 months.
      Purified protein derivative (PPD) was positive (> 10 mm) in all but one patient
      in whom it was performed (six of seven). Except tuberculous otitis, which occured
      without reactive lymphadenitis, this was present in 50% of the rest (six of the
      12). In all cases a biopsy was required for diagnosis. Only in four patients, all
      with pharyngeal locations, was coincident pulmonary tuberculosis confirmed. One
      patient with tuberculous otitis developed meningitis and died; three additional
      patients (two with otitis) were cured but with sequelae; the evolution of the
      remaining patients was satisfactory with medical therapy. CONCLUSIONS: Extra
      laryngeal head and neck tuberculosis has a slow course. The diagnosis is
      difficult due to the common absence of lung involvement and the usual
      requirements for biopsy procedures. The outcome is usually favorable with
      antituberculous drugs alone although in tuberculous otitis there are
      possibilities of complications.

PMID- 11284923
TI  - The ESP culture system for drug susceptibilities of Mycobacterium avium complex.
AB  - OBJECTIVE: To validate the non-radiometric, broth-based ESP system for
      determining Mycobacterium avium complex (MAC) susceptibilities. METHODS: MAC
      isolates from sterile body sites of 20 adult HIV-infected patients who were
      failing their present MAC regimen were identified. Susceptibilities were
      determined and comparisons made between the agar proportion method and the ESP
      system for clarithromycin, ethambutol, sparfloxacin and cycloserine. RESULTS:
      Ninety-nine percent of the MICS generated by the ESP system user identical to or
      lower than the MICs determined by the agar proportion METHOD: In vitro resistance
      was documented by the ESP system for 86% of the drugs that patients were taking
      at the time of breakthrough, and no resistance was seen to cycloserine, a drug
      that no patient was taking. CONCLUSIONS: The ESP system, a fast and reliable
      method for determining MAC susceptibilities, could be used to optimize MAC
      regimens in a timely fashion, avoid the use of ineffective drugs, minimize
      emerging resistance and ultimately improve outcome.

PMID- 11284924
TI  - Isolation rate, T-serotyping and susceptibility to antibiotics of Group A
      Streptococcus from pediatric infections in Athens.
AB  - OBJECTIVE: The epidemiology of Group A Streptococcus (GAS) in Greece is not
      known. We have therefore conducted this prospective study to investigate the
      isolation rate of GAS from pediatric specimens, determine T-serotype frequency
      and examine the susceptibility of GAS to penicillin, erythromycin and
      clindamycin. METHODS: Over a 3-year study-period (1993-95) 11 597 clinical
      specimens obtained from sick children were inoculated on appropriate culture
      media. The isolation and identification of GAS strains were assessed by
      conventional methods. T-typing was performed by slide agglutination. Serum
      opacity factor (OF) was detected by microwell METHOD: The susceptibility of the
      strains was tested by the Kirby Bauer method. RESULTS: GAS were isolated from
      1125 out of 11 597 (9.7%) clinical specimens, mostly from throat samples (15.6%).
      T-serotyping was performed in 652 GAS strains. A significant difference of the
      incidence of T-serotypes was observed within the 3 years studied (chi2 = 70.3, DF
      = 18, P < 0.001). The most dominant isolates were T-1 (25%), T-4 (20%) and T-12
      (16%) during 1993, 1994 and 1995, respectively. Non-typeable (NT) strains were
      4%. OF and hyaluronic acid were produced from 49.8% and 3% of the strains,
      respectively. All isolated strains were susceptible to penicillin and
      clindamycin. Resistance to erythromycin was 5.0-8.7% over the 3-year study
      period. CONCLUSIONS: There was a wide distribution of GAS T-serotypes in Athens
      and a significant change in their annual predominance. All strains were
      susceptible to penicillin and clindamycin, but a low level of erythromycin
      resistance was observed.

PMID- 11284925
TI  - Changes in lymphocyte subpopulations and CD3+/DR+ expression in sepsis.
AB  - OBJECTIVE: To detect lymphocyte subpopulations and CD3+/DR + expression in
      sepsis. METHODS: In a prospective clinical study we evaluated subpopulations of
      lymphocytes and percentage of CD3+/HLA-DR+ lymphocytes using two-color flow
      cytometry in 40 patients with sepsis and compared them with 34 healthy adults.
      RESULTS: Septic patients, when compared with healthy controls, have significantly
      lower percentage and absolute numbers of total T lymphocytes and CD4 T
      lymphocytes (P < 0.01). Absolute numbers of CD8 T lymphocytes, NK cells, CD3+/DR
      + lymphocytes and CD4/CD8 ratio were also decreased (P < 0.01). The percentage of
      B lymphocytes was increased (P < 0.01). CONCLUSION: Our results are in agreement
      with previous findings in patients with sepsis after major surgery or trauma. The
      decreases in the percentage and absolute numbers of circulating lymphocyte
      subsets in non-surgical sepsis could represent a general reaction to stress.
      Increased percentage of B lymphocytes is most probably related to the bacterial
      etiology of the disease.

PMID- 11284926
TI  - Ketolides-telithromycin, an example of a new class of antibacterial agents.
AB  - Ketolides are new medicinal chemical entities. They are obtained by removing the
      3-L-cladinose sugar moiety from erythronolide A and oxidation of the resulting 3
      hydroxyl. They were designed to overcome erythromycin A resistance within Gram
      positive cocci. The 3-keto group is responsible for the lack of induction of
      macrolide resistance, high stability in acidic environments, and the ability to
      overcome resistance due to methylation of 23SrRNA. The C11-C12 carbamate
      ketolides are able to overcome efflux and hydrolysis mechanisms of resistance and
      possess additional mechanisms of action at the ribosome level in comparison with
      erythromycin A. The nature of the side-chain substituting the C11-C12 carbamate
      residue is responsible for enhancing the in vitro and in vivo activities in
      comparison with clarithromycin, for the pharmacodynamic and pharmacokinetic
      properties, for the intracellular features, and for tolerance. This C11-C12 side
      chain is supporting the development of new ketolides.

PMID- 11284927
TI  - Towards a European strategy for controlling antibiotic resistance Nijmegen,
      Holland August 29-31, 1999.
AB  - A group of experts met under the auspices of the European Science Foundation, the
      European Medical Research Council and the European Society of Clinical
      Microbiology and Infectious Diseases to discuss formulation of a European
      strategy on the control of antibiotic resistance in Europe. This is a report of
      the meeting which was used as the basis for a European Commission grant
      application. The need for a common strategy to make best use of scarce resources
      was agreed and it was concluded that the first stage (discussed in this article)
      is to collate existing data on resistance rates, antibiotic consumption,
      antibiotic stewardship, infection control and molecular typing methods. Consensus
      reached from analysis of these data can direct us to the most appropriate
      controlled trials. While it is accepted that there is a widely held perception
      that the medical profession has been slow to react to the problem of antibiotic
      resistance, much more work still needs to be carried out before we can recommend,
      implement and trial definitive control measures. In the meantime, however, all
      reasonable efforts should be made to reduce antibiotic consumption without
      compromising patient care, establish cost-effective surveillance systems using
      existing laboratory generated data, improve hygiene in our hospitals and better
      define the molecular basis of antibiotic resistance.

PMID- 11284928
TI  - Nasopharyngeal carriage and antibacterial susceptibility of Streptococcus
      pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in Estonian
      children.

PMID- 11284929
TI  - The effect of albumin, globulin, pus and dead bacteria in aerobic and anaerobic
      conditions on the antibacterial activity of moxifloxacin, trovafloxacin and
      ciprofloxacin against Streptococcus pneumoniae, Staphylococcus aureus and
      Escherichia coli.

PMID- 11284930
TI  - Catalase-negative Staphylococcus aureus: a rare isolate of human infection.

PMID- 11284931
TI  - Nosocomial listeria gastroenteritis in a newborn, confirmed by random
      amplification of polymorphic DNA.

PMID- 11284932
TI  - Low-level resistance to fluoroquinolones among Salmonella and Shigella.

PMID- 11284933
TI  - Apparently false-positive blood cultures due to autolyzed Streptococcus
      pneumoniae.

PMID- 11284934
TI  - In vitro and in vivo synergistic activity of colistin, rifampin, and amikacin
      against a multiresistant Pseudomonas aeruginosa isolate.

PMID- 11284935
TI  - Emerging infections--a coordinated European approach.

PMID- 11284936
TI  - Definite streptococcus bovis endocarditis: characteristics in 20 patients.
AB  - OBJECTIVE: To determine the specific characteristics of Streptococcus bovis
      infective endocarditis (IE) by reviewing our own experience of S. bovis IE.
      METHODS: Twenty episodes of definite S. bovis IE were reviewed in 20 patients
      hospitalized from 1980 to 1996. RESULTS: The mean age was 62 +/- 14 years, and 14
      (70%) patients had no known predisposing cardiac condition. The principal
      antimicrobials used were penicillin G (N = 10) and amoxycillin (N = 8). Surgery
      was required in four (20%) patients. Neurologic complications occurred in eight
      (40%) patients, after initiation of therapy in six (75%) (mean time: 14 days). An
      unfavorable outcome was observed in four of 20 patients and tended to be more
      frequent in patients who had had neurologic complications (P = 0.10). Colonic
      tumors were present in 11 of 16 (69%) patients. CONCLUSIONS: Advanced age,
      occurrence of IE on presumably normal valves, high rate of neurologic
      complications, associated gastrointestinal diseases and low mortality rate during
      initial follow-up are characteristic features of S. bovis IE observed in this
      study.

PMID- 11284937
TI  - In vitro activity of a new echinocandin, LY303366, and comparison with
      fluconazole, flucytosine and amphotericin B against Candida species.
AB  - OBJECTIVE: To investigate the in vitro activity of LY303366 (LY) against Candida
      isolates comprising nine different species and comparison with fluconazole (FLU),
      flucytosine (5FC) and amphotericin B (AMB). METHODS: The method used was a
      microtitre modification of the NCCLS M27-A accepted standard using either RPMI
      1640 with 2% glucose (5FC and FLU) or antibiotic medium 3 with 2% glucose (LY and
      AMB). The minimum inhibitory concentration (MIC) was the lowest drug
      concentration that reduced growth by 80% compared with the drug-free control.
      Minimum fungicidal concentrations (MFCs; 99% kill) were also determined for all
      isolates for LY and AMB. RESULTS: Overall, 58 of 105 (55.2%) isolates were
      resistant to FLU (MIC < or = 16 mg/L). There was no relationship between FLU and
      LY MICs for C. albicans or non-albicans species. For all isolates, geometric mean
      (GM) MIC values and ranges (in mg/L) were: LY 0.011 and < or = 0.001-16, FLU 8.72
      and < or = 0.125- > 128, 5FC 0.393 and < or = 0.03- > 32, AMB 0.046 and 0.008
      0.125. Differences in susceptibility to LY were seen: C. parapsilosis (n = 12, GM
      0.4 and range 0.125-16) and C. guilliermondii (n = 8, GM 0.46 and range 0.25-1)
      were both found to be significantly less susceptible to LY than all other species
      (P < or = 0.05). For all isolates, geometric mean MFC values and ranges (in mg/L)
      were: LY 0.032 and 0.002-16, AMB 0.143 and 0.03-2. The MFC value was the same as
      or only one drug dilution higher than the MIC value for 69.5% and 48.6% of
      isolates tested for LY and AMB, respectively. Tolerance was described in 13.3%
      and 5.7% of isolates for LY and AMB, respectively. A reproducibility study
      performed on 20% of the isolates showed that 90.5%, 100%, 95.2% and 100% of
      isolates retested were the same or within one well of the original MIC value for
      LY, FLU, 5FC and AMB, respectively. CONCLUSIONS: LY303366 shows promising
      antifungal activity in vitro and warrants further in vivo investigation.

PMID- 11284938
TI  - Chloramphenicol treatment for vancomycin-resistant Enterococcus faecium
      bacteremia.
AB  - OBJECTIVE: To evaluate the results of treating vancomycin-resistant Enterococcus
      faecium (VREF) bacteremia with chloramphenicol. METHODS: We retrospectively
      reviewed the charts of all adult patients with VREF bacteremia treated with
      chloramphenicol during the calendar year 1998 at a 522-bed tertiary referral
      center in New York City. Patients were identified by reviewing microbiology
      laboratory records. Patients with clinically significant VREF bacteremia who
      received chloramphenicol for at least 48 h were included in the study. Clinical
      and microbiological outcomes were determined. Microbiological and molecular tests
      were performed on a small representative sample of isolates to identify the
      presence of resistance mechanisms and to look for similarity among the isolates.
      RESULTS: Seven episodes of significant VREF bacteremia occurred in six patients.
      Mean age was 54 years. All patients had cancer and three had severe neutropenia.
      Five of seven episodes were associated with chronic indwelling devices, but in
      only one of these cases was the device removed. All isolates were susceptible to
      chloramphenicol in vitro. All six microbiologically evaluable episodes had a
      favorable response to chloramphenicol treatment, and four of seven (57%)
      clinically evaluable episodes had favorable outcomes. Only one death may have
      been due to VREF bacteremia, so the maximal attributable mortality was 14%. The
      three representative samples that were tested further were indistinguishable from
      one another and they displayed no evidence of resistance mechanisms. CONCLUSIONS:
      In a cohort of severely ill cancer patients, chloramphenicol was effective in
      treating VREF bacteremia. The use of chloramphenicol should be considered in
      treating infections with this highly resistant organism, where therapeutic
      options are limited.

PMID- 11284939
TI  - Modified Granada Agar Medium for the detection of group B Streptococcus carriage
      in pregnant women.
AB  - OBJECTIVES: To improve the detection rate of group B streptococci (GBS) in
      pregnant women, aiming at the prevention of early-onset septicemia in the
      newborn. METHODS: The yield from culturing two sites, vaginal and anorectal, on a
      Modified Granada Medium (MGM) was compared with our standard approach of
      culturing a vaginal swab on blood agar (BA). RESULTS: Samples were processed from
      430 consecutive pregnant women. GBS was isolated from the vagina in 11.6% with
      BA, and in 13.7% with MGM. In 17.0% of anorectal samples, GBS was identified with
      MGM. The combination of both sites and media had a yield of 20.0%. MGM identified
      all but six (2%) of 310 GBS strains after aerobic incubation, with use of a cover
      slide, and missed only three strains (1%) after anaerobic incubation.
      CONCLUSIONS: Separate culture of vaginal and anorectal samples using the same MGM
      agar plate resulted in an increase in detection rate for GBS of 76% as compared
      to BA alone. The technique is simple and results are available after overnight
      incubation. MGM was confirmed as a specific medium for the identification of GBS,
      with a sensitivity of 98-99%.

PMID- 11284940
TI  - Prevention of group B streptococcal neonatal disease: a plea for a European
      consensus.

PMID- 11284941
TI  - The use of antibiotic-containing bead chains in the treatment of chronic bone
      infections.
AB  - The implantation of gentamicin polymethylmethacrylate (PMMA) chains or minichains
      into infected osteomyelitic cavities is a well-established local antibiotic
      therapy supplementary to radical debridement. The gentamicin concentrations
      achieved at the site of infection are far above the MICs for most common
      pathogens in chronic osteomyelitis. Serum and urine concentrations are low, and
      nephrotoxic and ototoxic side-effects of this form of gentamicin application are
      not to be feared. Under local antibiotic therapy with gentamicin PMMA chains,
      primary wound healing as in aseptic surgery can be expected. Prolonged systemic
      antibiotic therapy is unnecessary. In a series of 405 cases, a success rate of
      90.4% was obtained.

PMID- 11284942
TI  - Therapy of ventilator-associated pneumonia: the Tarragona strategy.

PMID- 11284943
TI  - A case of superficial septic thrombophlebitis in a varicose vein caused by
      Salmonella panama.

PMID- 11284944
TI  - Molecular diagnosis of recurrent Streptococcus mutans endocarditis by PCR
      amplification and sequencing.

PMID- 11284945
TI  - In vitro activity of moxifloxacin against Stenotrophomonas maltophilia blood
      isolates from patients with hematologic malignancies.

PMID- 11284946
TI  - Bactericidal activity in cerebrospinal fluid by treating meningitis caused by
      Stomatococcus mucilaginosus with rifampicin, cefotaxime and vancomycin in a
      neutropenic child.

PMID- 11284947
TI  - Nasopharyngeal carriage of penicillin-resistant, macrolide-resistant and multiply
      resistant Streptococcus pneumoniae in day-care centers in Sofia, Bulgaria.

PMID- 11284948
TI  - Bactericidal activity of moxifloxacin against pneumococci.

PMID- 11284949
TI  - Late diagnosis of histoplasmosis in a Brazilian patient with acquired
      immunodeficiency syndrome.

PMID- 11284950
TI  - Does HPV testing have a role in primary cervical screening?

PMID- 11284951
TI  - Significance of high-risk human papillomavirus detection by polymerase chain
      reaction in primary cervical cancer screening.
AB  - The purposes of this study were to evaluate the incidence of high-risk human
      papillomavirus (HPV) infection by polymerase chain reaction (PCR) and to assess
      its diagnostic usefulness in primary cervical screening. PCR testing for HPV type
      16, 18, 31 and 33 was performed on 1305 specimens obtained during routine
      cervical cancer screening. We analysed the concurrent cervical smears and biopsy,
      and correlated them with the HPV infection status. We also evaluated
      histologically-proven cases with ASCUS smears according to HPV infection. HPV DNA
      was identified in eight (0.7%) of 1144 cytologically normal patients; nine
      (10.5%) of 86 ASCUS; seven (25.0%) of 28 LSIL; 26 (78.8%) of 33 HSIL; and in all
      of three squamous cell carcinomas (SCC). HPV positivity was significantly
      associated with cytohistological diagnosis for HSIL of more. In addition, HPV
      positive ASCUS cases were found to be associated with histological abnormality
      rather than HPV-negative. The results indicate that high-risk HPV testing by PCR
      could be a useful adjunct tool for Pap smear in primary cervical screening. The
      combination of Pap smear and high-risk HPV testing by PCR might reduce
      unnecessary colposcopy-guided biopsy of women with cytological diagnosis of
      ASCUS.

PMID- 11284952
TI  - Performance of cytology and colposcopy in diagnosis of cervical intraepithelial
      neoplasia (CIN) in HIV-positive and HIV-negative women.
AB  - As part of an extensive multi-institutional DIANAIDS-HIV-HPV-SIL project run in
      Italy (co-ordinated by ISS), the present study compares the performance
      (sensitivity, specificity, agreement) of routine cervical smear cytology with
      that of colposcopy in the detection of histologically-confirmed CIN lesions in 37
      HIV-positive and 21 HIV-negative women, belonging to the DIANAIDS cohort of 459
      women. All women were subjected to a cervical smear, colposcopy and biopsy,
      making possible the pairwise comparison of these techniques. In the whole series
      of HIV-positive and HIV-negative women, cytology had a sensitivity of 86.9% and
      specificity of 83.3%, the sensitivity of grade 2 abnormality on colposcopy
      against histology being 82.6% and specificity, 33.3%. No statistically
      significant difference was observed in the performance of Pap smears between the
      HIV-positive and HIV-negative women. The sensitivity of cytology was 89.7% vs
      82.4% and the specificity, 75% vs 100%. For colposcopy, the sensitivity was 79.3%
      vs 88.2% and the specificity, 75% vs 50%. These data suggest that cervical Pap
      smear cytology is a highly sensitive and specific diagnostic tool in the clinical
      monitoring of lower genital tract pathology in HIV-positive women. Colposcopy, on
      the other hand, proved to be a somewhat less accurate diagnostic tool in these
      women.

PMID- 11284953
TI  - Cervical cytology EQA--the Northern experience.
AB  - The experience of the Northern region using the 1995 draft National
      Gynaecological Cervical Cytology External Quality Assurance (EQA) Scheme is
      given. Over three rounds, 390 staff reporting Cervical Cytology took part, and
      using a cumulative non-numeric marking scheme, five participants were deemed
      "unacceptable" at the end of three rounds. A total of 3450 responses were given
      to the 40 test slides used, with an overall false-positive rate of 5.9% and a
      false-negative rate of 1.4%. Grading was assessed for pathologists, and many
      appeared to perform badly by accumulating discrepancies for non-clinically
      significant grading differences. The problems of slide selection/staining and
      grading consistency/accuracy are highlighted. This EQA scheme serves its dual
      function of education and identifying poor performance. It must be seen as a
      viable EQA scheme, although other options must be considered, given advances in
      technology.

PMID- 11284954
TI  - Can British terminology in cervical cytology survive liquid-based cytology?

PMID- 11284955
TI  - The cytopathology of ductal carcinoma in situ of the breast. A detailed analysis
      of fine needle aspiration cytology of 58 cases compared with 101 invasive ductal
      carcinomas.
AB  - Bonzanini M., Gilioli E., Brancato B., Cristofori A., Bricolo D., Natale N.,
      Valentini A., and Dalla Palma P. (2001)Cytopathology 12, 107-119. The
      cytopathology of ductal carcinoma in situ of the breast. A detailed analysis of
      fine needle aspiration cytology of 58 cases compared with 101 invasive ductal
      carcinomas. The existence of cytological findings that discriminate ductal
      carcinoma in situ (DCIS) of the breast from invasive ductal carcinoma (IDC) has
      not been unanimously accepted and the role of fine needle aspiration cytology
      (FNAC) remains controversial. We report the cytological findings of a large
      series of FNAC from histologically proven DCIS compared with those of ductal
      carcinomas having a different extent of the invasive component. The association
      of high cohesiveness of atypical cells and absence of tubular aggregates showed
      good sensitivity (SE) and specificity (SP) for the diagnosis of DCIS vs IDC. The
      simultaneous presence of necrotic background, atypical cells with abundant
      eosinophilic cytoplasm and a low percentage of single malignant cells resulted in
      low sensitivity but high specificity and positive predictive value (PPV) for
      differential cytological diagnosis of DCIS vs IDC.

PMID- 11284956
TI  - Microfilariae in association with neoplastic lesions: report of five cases.
AB  - Microfilariae and adult filarial worms have occasionally been detected in
      association with neoplastic lesions in cytological smears. The presence of
      microfilariae along with neoplasms is generally regarded as a chance association,
      yet some authors suggest that such parasitic infestations may be a causative
      factor for tumourigenesis. There are only a few reported cases in cytology
      literature documenting this association. We report the presence of microfilariae
      in routine cytology smears from one benign and four malignant tumours.
      Microfilariae could not be identified on histopathology available in four of
      these cases.

PMID- 11284957
TI  - Warthin-like tumour of the thyroid--the fine needle aspiration cytology features.

PMID- 11284958
TI  - Fine needle aspiration biopsy in Western Jamaica: preliminary observations.

PMID- 11284959
TI  - Efficacy of Ki-67 antigen staining in Papanicolaou (pap) smears in postmenopausal
      women with atypia--an audit.

PMID- 11284960
TI  - Re "ABC2"; several paces forward but a big leap back for cervical cancer audit.

PMID- 11284961
TI  - Localization of mitochondrial ribosomal RNA on the chromatoid bodies of marine
      planarian polyclad embryos.
AB  - Electron-dense cytoplasmic structures, referred to as chromatoid bodies, are
      observed in the somatic stem cells, called neoblasts, and germline cells in adult
      planarians. Although it has been revealed that the chromatoid bodies
      morphologically resemble germline granules in Drosophila and Xenopus embryos,
      what essential role it plays in the planarian has remained unclear. In the
      present study, to examine whether chromatoid bodies in planarian embryos are
      responsible for germline formation, the presence and behavior of chromatoid
      bodies during embryogenesis were examined. Mitochondrial large ribosomal RNA and
      mitochondrial small ribosomal RNA were used as candidate markers for components
      of the chromatoid body. Starting from the fertilized egg, extramitochondrial
      signals of both RNA (mtrRNA) were observed. At the ultrastructural level, mtrRNA
      were localized on the surface of the chromatoid bodies. At subsequent stages, the
      signals of mtrRNA were observed in certain restricted blastomeres that contribute
      to the formation of larval structures. The signals gradually decreased from the
      gastrula stage. These results suggest that the chromatoid bodies associated with
      mtrRNA in embryogenesis are not germline granules. The chromatoid bodies of
      blastomeres may be concerned with the toti- or pluripotency and cell
      differentiation as proposed in adult planarian neoblasts.

PMID- 11284962
TI  - Human truncated Smad 6 (Smad 6s) inhibits the BMP pathway in Xenopus laevis.
AB  - A previously identified truncated form of the human Smad 6 gene containing a
      unique 12 amino acid motif at its N-terminus was studied. We have named this
      truncated form of the gene Smad 6s, for 'short-form', to distinguish it from the
      full-length form (Smad 6fl). Reverse transcription-polymerase chain reaction and
      immunohistochemistry revealed that Smad 6s has a unique pattern of expression in
      human coronary tissue and is upregulated in diseased heart tissue. We used the
      expression of human Smad 6s in Xenopus laevis as a model system to assess Smad 6s
      function. Injection of Smad 6fl RNA (4-cell embryos, 2 x ventral) produced
      tadpoles with partial secondary axes. In contrast, Smad 6s RNA injected in a
      similar manner produced tadpoles with a severe 'head-only' phenotype with no
      morphological appearance of a secondary axis. Mutant Smad 6s RNA lacking the
      unique 12 amino acids at the N-terminus of the Smad 6s isoform produced no
      embryonic phenotype, suggesting that this region is important in conferring
      biological activity. Ectodermal explant assays show that Smad 6s has activity
      consistent with being a BMP antagonist and can synergize with and enhance the
      activities of the activin and fibroblast growth factor pathways, all of which are
      novel findings in this study.

PMID- 11284963
TI  - Subtractive hybridization reveals tissue-specific expression of ahnak during
      embryonic development.
AB  - The gene product ahnak has been identified from extra-embryonic mesoderm cDNA
      enriched using a subtractive hybridization approach modified for using small
      amounts of starting material. Clones for cyclin D2 and H19 have also been
      isolated as being preferentially enriched in the extra-embryonic mesoderm
      compared with the embryo proper of embryonic day (E) 7.5 neural plate stage mouse
      embryos. The differential expression of these genes was confirmed at gastrulation
      stage using in situ hybridization. More detailed analysis of the human genomic
      ahnak sequence suggests that its highly repetitive structure was formed by
      unequal cross-over and gene conversion. During organogenesis, ahnak is expressed
      in a variety of tissues, including migratory mesenchyme. By E12.5, the major site
      of expression of ahnak is craniofacial mesenchyme. Immunohistochemical analysis
      has shown that ahnak protein is expressed mainly at the cell membrane of
      migratory mesenchymal cells, primarily in the nucleus of bone growth plate cells
      and mostly in the cytoplasm of differentiating nasal epithelia. The potential
      functions of ahnak are discussed in light of these results.

PMID- 11284964
TI  - Involvement of Rel/NF-kappaB in regulation of ascidian notochord formation.
AB  - The Rel/NF-kappaB family is known to be involved in a wide variety of biological
      processes, including morphogenesis. In the present study, two protochordate cDNA
      clones encoding Rel/NF-kappaB proteins, named As-rel1 and As-rel2, were isolated
      from a fertilized egg cDNA library of the ascidian Halocynthia roretzi. The As
      rel1 protein is a typical Rel/NF-kappaB family member, containing a Rel homology
      domain, a nuclear localization sequence and a C-terminal putative transcription
      activation domain, while the As-rel2 protein is a novel Rel/NF-kappaB family
      member that lacks a nuclear localization sequence and the C-terminal domain.
      Northern blot analyses showed that both transcripts were maternally expressed and
      that their expression changed during development of H. roretzi embryos. Although
      injection of the As-rel2 mRNA into H. roretzi fertilized eggs had little effect
      on embryonic development, injection of the As-rel1 mRNA interfered greatly with
      notochord formation, resulting in a shortened tail with a reduced number of
      notochord cells. In contrast, embryos co-injected with As-rel1 and As-rel2 mRNA
      developed normally, indicating that the As-rel2 protein rescued the defect in
      notochord formation induced by the injection of As-rel1 mRNA alone. These results
      strongly suggest that the As-rel1 protein functions as a suppressor in ascidian
      notochord formation, while the As-rel2 protein has an antagonistic effect on the
      action of the As-rel1 protein.

PMID- 11284965
TI  - Possible role for the c-ski gene in the proliferation of myogenic cells in
      regenerating skeletal muscles of rats.
AB  - Skeletal muscle regeneration after injury involves various processes, such as
      infiltration by inflammatory cells, the proliferation of satellite cells and
      fusion to myotubes. The c-ski nuclear protein has been implicated in the control
      of cell proliferation and/or terminal differentiation in the growth of skeletal
      muscle. However, there have been no reports concerning the involution of c-ski in
      the regeneration of injured skeletal muscle in mammals. A possible role for c-ski
      in the proliferation of myogenic cells in rat skeletal muscle during regeneration
      has been investigated with the assistance of in vitro experiments with L6
      skeletal muscle cells. The expression levels of c-ski mRNA in regenerating
      tissues increased to approximately threefold that of intact tissues at 2 days
      after injury and decreased to normal levels at 2 weeks after injury. Many
      mononuclear cells among the Ski-positive cells expressed desmin and proliferating
      cell nuclear antigen, indicating that Ski-producing cells include the
      proliferating myogenic cells. The proliferation of L6 cells was significantly
      retarded by expression of the antisense ski gene. The results of the present
      study reveal that the c-ski gene plays an important role in the proliferation of
      myogenic cells in the regeneration of injured skeletal muscle.

PMID- 11284966
TI  - Fibroblast growth factor-induced gene expression and cartilage pattern formation
      in chick limb bud recombinants.
AB  - To clarify the roles of fibroblast growth factors (FGF) in limb cartilage pattern
      formation, the effects of various FGF on recombinant limbs that were composed of
      dissociated and reaggregated mesoderm and ectodermal jackets were examined.
      Fibroblast growth factor-soaked beads were inserted just under the apical
      ectodermal ridge (AER) of recombinant limbs and the recombinant limbs were
      grafted and allowed to develop. Control recombinant limbs without FGF beads
      formed one or two cartilage elements. Recombinants with FGF-4 beads formed up to
      five cartilage elements, which were aligned along the anteroposterior (AP) axis.
      Each cartilage element showed digit-like segmentation. In contrast, recombinants
      with FGF-2 beads showed formation of multiple thick and unsegmented cartilage
      rods, which elongated inside and outside the AP plane from the distal end of the
      recombinants. Recombinants with FGF-8 beads formed a truncated cartilage pattern
      and recombinants with FGF-10 beads formed a cartilage pattern similar to that of
      the control recombinants. The expression of the Fgf-8, Msx-1 and Hoxa-13 genes in
      the developing recombinant limbs were examined. FGF-4 induced extension of the
      length of the Fgf-8-positive epidermis, or AER, along the AP axis 5 days after
      grafting, at which time the digits are specified. FGF-2 induced expansion of the
      Msx-1-positive area, first in the proximal direction and then along the
      dorsoventral axis. The functions of these FGF in recombinant and normal limb
      patterning are discussed in this paper.

PMID- 11284967
TI  - Position-specific and non-colinear expression of the planarian posterior
      (Abdominal-B-like) gene.
AB  - Hox genes are pivotal molecules in the control of morphogenesis along the
      anterior-posterior (AP) axis in various bilaterians. Planarians are key animals
      for understanding the evolution of the bilaterian body plan. Furthermore, they
      are also known for their strong regeneration ability and are thought to use the
      Hox genes in the process of reconstruction of the AP axis. In the present paper,
      the identification and analysis of expression of two posterior (Abdominal-B-like)
      genes, DjAbd-Ba and DjAbd-Bb, is reported in the planarian Dugesia japonica.
      DjAbd-Ba is expressed in the entire tail region and its anterior boundary is the
      posterior pharyngeal region. In contrast, DjAbd-Bb is expressed in several types
      of cells throughout the body. During regeneration, the expression of DjAbd-Ba
      rapidly recovers a pattern similar to that in the normal worm. These findings
      suggest the possibility that DjAbd-Ba is involved in the specification of the
      tail region. The anterior boundary of the expression domain of the posterior gene
      DjAbd-Ba is anterior to the domains of the central genes Plox4-Dj and Plox5-Dj.
      These expression patterns of planarian Hox genes seem out of the rule of spatial
      colinearity and may reflect an ancestral feature of bilaterian Hox genes.

PMID- 11284968
TI  - Early expressed genes showing a dichotomous developing pattern in the lancelet
      embryo.
AB  - Lancelets (amphioxus), although showing the most similar anatomical features to
      vertebrates, never develop a vertebrate-like head but rather several structures
      specific to this animal. The lancelet anatomical specificity seems to be
      traceable to early developmental stages, such as the vertebrate dorsal and
      anterior-posterior determinations. The BMP and Wnt proteins play important roles
      in establishing the early basis of the dorsal structures and the head in
      vertebrates. The early behavior of BMP and Wnt may be also related to the
      specific body structures of lancelets. The expression patterns of a dpp-related
      gene, Bbbmp2/4, and two wnt-related genes, Bbwnt7 and Bbwnt8, have been studied
      in comparison with those of brachyury and Hnf-3beta class genes. The temporal
      expression patterns of these genes are similar to those of vertebrates; Bbbmp2/4
      and Bbwnt8 are first expressed in the invaginating primitive gut and the
      equatorial region, respectively, at the initial gastrula stage. However, spatial
      expression pattern of Bbbmp2/4 differs significantly from the vertebrate
      cognates. It is expressed in the mid-dorsal inner layer of gastrulae and widely
      in the anterior region, in which vertebrates block BMP signaling. The present
      study suggests that the lancelet embryo may have two distinct developmental
      domains from the gastrula stage, the domains of which coincide later with the
      lateral diverticular and the somitocoelomic regions. The embryonic origin of the
      anterior-specific structures in lancelets corresponds to the anterior domain
      where Bbbmp2/4 is continuously expressed.

PMID- 11284969
TI  - Evidence for multiple sequences and factors involved in c-myc RNA stability
      during amphibian oogenesis.
AB  - To investigate the molecular mechanisms regulating c-myc RNA stability during
      late amphibian oogenesis, a heterologous system was used in which synthetic
      Xenopus laevis c-myc transcripts, progressively deleted from their 3' end, were
      injected into the cytoplasm of two different host axolotl (Ambystoma mexicanum)
      cells: stage VI oocytes and progesterone-matured oocytes (unfertilized eggs;
      UFE). This in vivo strategy allowed the behavior of the exogenous c-myc
      transcripts to be followed and different regions involved in the stability of
      each intermediate deleted molecule to be identified. Interestingly, these
      specific regions differ in the two cellular contexts. In oocytes, two stabilizing
      regions are located in the 3' untranslated region (UTR) and two in the coding
      sequence (exons II and III) of the RNA. In UFE, the stabilizing regions
      correspond to the first part of the 3' UTR and to the first part of exon II.
      However, in UFE, the majority of synthetic transcripts are degraded. This
      degradation is a consequence of nuclear factors delivered after germinal vesicle
      breakdown and specifically acting on targeted regions of the RNA. To test the
      direct implication of these nuclear factors in c-myc RNA degradation, an in vitro
      system was set up using axolotl germinal vesicle extracts that mimic the in vivo
      results and confirm the existence of specific destabilizing factors. In vitro
      analysis revealed that two populations of nuclear molecules are implicated: one
      of 4.4-5S (50-65 kDa) and the second of 5.4-6S (90-110 kDa). These degrading
      nuclear factors act preferentially on the coding region of the c-myc RNA and
      appear to be conserved between axolotl and Xenopus. Thus, this experimental
      approach has allowed the identification of specific stabilizing sequences in c
      myc RNA and the temporal identification of the different factors (cytoplasmic
      and/or nuclear) involved in post-transcriptional regulation of this RNA during
      oogenesis.

PMID- 11284970
TI  - Effects of Ca2+ on flavin-linked complex enzymes in mitochondria isolated from
      eggs and embryos of sea urchin.
AB  - Mitochondria isolated from sea urchin embryos in early development show almost
      the same activities of cytochrome c oxidase and flavin-linked complex enzymes,
      which are estimated by cytochrome c reductases as in those isolated from
      unfertilized eggs. The activities of these cytochrome c reductases are inhibited
      by Ca2+ at above 10-5 M more strongly than cytochrome c oxidase. To investigate
      the changes in intramitochondrial Ca2+ concentration at fertilization, the
      activity of pyruvate dehydrogenase, another mitochondrial enzyme, was measured.
      The activity of this enzyme was controlled by phosphorylation and Ca2+-dependent
      dephosphorylation of the catalytic unit. The enzyme activity increased for 30 min
      after fertilization, decreased and became close to zero within ~60 min. Then, the
      activity appreciably increased again after hatching. This seems to reflect
      changes in the intramitochondrial Ca2+ concentration. The enzyme activity was
      enhanced by pre-incubation with Ca2+ at concentrations up to 10-5 M but was made
      quite low at above 10-4 M Ca2+ and 10-3 M adenosine triphosphate. Although the
      changes in pyruvate dehydrogenase activity observed at fertilization will reflect
      the changes in the intramitochondrial calcium concentration, the
      intramitochondrial Ca2+ concentration of unfertilized eggs cannot be estimated
      from these results because high (> 10-4 M) or low (10-6 M) Ca2+ can inhibit the
      enzyme. Measurement of respiration of a single egg showed that injection of
      ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid released the
      mitochondrial electron transport in the unfertilized egg. The possibility that
      changes in intramitochondrial calcium concentration occur at fertilization is
      discussed in relation to activation of both mitochondrial respiration and
      pyruvate dehydrogenase.

PMID- 11284971
TI  - Reproducibility, validity, and responsiveness of a disease-specific symptom
      questionnaire for gastroesophageal reflux disease.
AB  - The purpose of this study was to establish the reproducibility, validity, and
      responsiveness of a symptom questionnaire to assess patients with
      gastroesophageal reflux disease (GERD). A total of 300 patients with GERD
      completed questionnaires before and 6 months after laparoscopic Nissen
      fundoplication. Forty-six GERD patients who continued on omeprazole served as
      controls. Lower esophageal sphincter pressure, 24-h pH, and quality of life
      (SF36) were measured at baseline and follow-up. Reproducibility was calculated as
      an intraclass correlation coefficient (ICC) from a repeated-measures analysis of
      variance on symptom scores (SS) on two consecutive days. Validity was established
      by correlating SS with 24-h pH and SF36 scores. Responsiveness was calculated as
      the the ratio of the mean paired difference in score in the surgical group to the
      within-subject variability in control subjects. Reproducibility was very high, as
      revealed by an ICC of 0.92. Strong correlations between SS and SF36 scores at
      baseline and after surgery demonstrated high cross-sectional validity.
      Correlation between change in SS and change in pH, SF36 pain, general health, and
      physical health scores demonstrated longitudinal validity. The mean (95%
      confidence interval) paired differences in SS were 25.6 (23.7, 27.5) in the study
      and 2.0 (-3.2, 7.3) in the control groups, and the responsive index was 1.0. The
      estimated minimally important clinical difference was 7. We conclude that the
      symptom score is a reproducible, valid, and responsive instrument for assessing
      symptoms caused by GERD.

PMID- 11284972
TI  - Long-term use of acid-suppressive therapy after the endoscopic diagnosis of
      reflux esophagitis.
AB  - A study was carried out in a group of patients in whom reflux esophagitis was
      diagnosed 4.5-7.5 years previously in order to assess current complaints and use
      of medication. A questionnaire was mailed to all patients in whom reflux
      esophagitis was diagnosed. Patients were asked about the presence of reflux
      complaints. Use of medication was assessed (continuous, intermittent, or on
      demand). In the 3-year period, reflux esophagitis was diagnosed in 312 patients
      (195 men, 117 women, mean age 59.6 years, range 17-96 years). The questionnaire
      was mailed to 246 patients, of whom 172 (70%) responded. Of these, 146 (85%) used
      acid-suppressive therapy. One hundred and eight (74%) used drugs on a daily
      basis, 31 on demand and 19 prophylactically in order to prevent the occurrence of
      reflux complaints. Despite the use of medication, patients suffered significantly
      more often from reflux complaints than did individuals who did not use any
      medication. It is concluded that the majority of patients (85%) still use acid
      suppressive therapy and, in 74% of cases, on a daily basis. Maintenance therapy
      cannot prevent clinical relapse.

PMID- 11284973
TI  - Rising incidence of esophageal adenocarcinoma in Western countries: is it
      possible to identify a population at risk?
AB  - Symptomatic gastroesophageal reflux disease (GERD) and Barrett's mucosa are risk
      factors for esophageal adenocarcinoma (ADC). The aim of this study was to analyze
      the anthropometric features and prevalence of GERD in patients with ADC compared
      with patients with squamous cell carcinoma (SCC) and control subjects. A total of
      262 patients with ADC and 302 with SCC were enrolled consecutively. A control
      group of 262 individuals, sex and age matched to the ADC group, and an additional
      group of 138 patients with GERD confirmed by 24-h pH monitoring were used for
      comparison. The prevalence of symptomatic GERD was 32.4% in the subgroup of
      patients with Barrett's ADC (male-female=6.4:1; mean age=62 years) vs. 8% in
      those with gastric cardia carcinoma (P< 0.01), 3% in the SCC group (P< 0.01), and
      10% in the control group (P< 0.01). ADC patients, controls and refluxers had
      similar body mass index (BMI) that was significantly higher than in the SCC group
      (P< 0.05). Whether surveillance endoscopy is indicated in men over 50 years with
      a long-lasting history of GERD and a BMI >25 remains to be determined.

PMID- 11284974
TI  - Heller's myotomy: thoracoscopic or laparoscopic?
AB  - Cardiomyotomy is now usually performed using a minimally invasive approach. A
      consecutive series of 18 patients with an intention to treat thoracoscopically
      were followed by the same number of patients treated laparoscopically. Both
      groups have been followed prospectively for a minimum of 2 years. The groups were
      well matched for age, symptom duration, preoperative lower esophageal sphincter
      pressure, and number having undergone balloon dilatation. There was one
      conversion from a thoracoscopic to a laparoscopic approach so that, for the
      purpose of analysis, there are 17 in the thoracoscopic group and 19 in the
      laparoscopic group. There was no difference in the average operating time, rate
      of conversion to open operation, mucosal breaches, or length of hospitalization.
      Nor was there any difference in dysphagia symptoms, with 14/17 having a
      satisfactory result after thoracoscopic myotomy and 18/19 after laparoscopic
      myotomy. Frequency of reflux symptoms was similar and, although mild reflux was
      common, only two patients required treatment with a proton pump blocker. In the
      treatment of achalasia, thoracoscopic and laparoscopic myotomy without
      fundoplication are equally effective in relieving dysphagia and have a similar
      safety profile.

PMID- 11284975
TI  - Reservoir and globe-type antireflux surgical techniques in intrathoracic
      esophagogastrostomies.
AB  - Gastroesophageal reflux is a major postoperative problem in esophageal patients
      with cancer, and the principal cause is resection of the lower esophageal
      sphincter. Two new antireflux operations to solve this problem were investigated.
      The number of patients studied was 139, with a male to female ratio of 5. The
      reservoir technique was applied to the first 50 patients and the globe technique
      was used in the remaining 89. Hospital mortality was 9.35%. Patient satisfaction
      from a reflux standpoint was excellent in 91.4%, good to fair in 6.5%, and poor
      in 2.1%. Postoperative barium swallow at the first, third, and sixth months
      showed no reflux in 93% of cases. Postoperative preanastomotic mean pressure was
      14.2 mmHg. Postoperative mucosal biopsies revealed a remarkable reduction in
      esophagitis. The radiologic, manometric, and histologic findings as well as the
      patient satisfaction rate suggest that these antireflux operations are suitable
      and effective for patients undergoing esophageal resection and intrathoracic
      esophagogastric anastomosis.

PMID- 11284976
TI  - Impact of gastric tube diameter on upper mediastinal anatomy after transhiatal
      esophagectomy.
AB  - The most common means of reconstructing the esophagus in patients undergoing
      transhiatal esophagectomy is by passing the stomach through the esophageal bed
      into the neck, where an esophagogastric anastomosis is fashioned. A number of
      factors need to be considered in mobilizing the stomach for transhiatal
      esophageal reconstruction: the stomach tube must have adequate blood supply and
      be wide enough to permit passage of solid food and yet narrow enough to
      facilitate emptying and to fit through the limited space of the upper
      mediastinum. The construction of a non-reversed, greater curvature gastric tube
      of approximately 4-5 cm diameter, supplied by the right gastroepiploic vessels,
      appears to accomplish all of these goals.

PMID- 11284977
TI  - Evaluation of the histologic effect of chemoradiation therapy for squamous cell
      carcinomas of the esophagus by assessing morphologic features of surgical
      specimens.
AB  - The histologic effects of chemoradiation therapy (CRT) for esophageal cancer,
      which determine the benefit obtained from a salvage operation, are difficult to
      evaluate preoperatively. We therefore investigated whether or not the morphologic
      features of esophageal cancer tissue after CRT can be correlated with the
      histologic features of the tissue. Seventy-six patients with advanced esophageal
      squamous cell carcinoma underwent CRT followed by esophagectomy. The effects of
      CRT were evaluated by histologic examination of the residual tumors in the
      surgical specimen and correlated with clinicopathologic factors, including
      postoperative prognosis. The histologic effects of CRT were used to classify
      tumors as grade 1 (CRT poorly effective; 23 cases, 30.3%); grade 2 (CRT
      moderately effective; 31 cases, 40.8%); or grade 3 (CRT completely effective with
      no residual tumors; 22 cases, 28.9%). Among the gross findings of the removed
      esophagus, significant correlation with the CRT effects was observed in the case
      of wall thickness and ulceration but not in the case of longitudinal tumor
      length. Tumors with no wall thickening or ulceration were never classified as
      grade 1, whereas tumors with both wall thickening and ulceration were frequently
      rated as grade 1 (18/30, 60%). Microscopic examination of grade 2 tumors (23/31,
      74.1%) revealed residual tumor cells growing below the mucosal layer, whereas
      tumor cells were exposed to the esophageal surface in 22 out of 23 patients with
      grade 1 tumors. The morphologic features after CRT can be used to evaluate its
      histologic effect, especially in the case of grade 1 tumors. However, the
      detection and prediction of grade 2 tumors remains difficult because of the
      presence of small amounts of residual tumor underneath the mucosa.

PMID- 11284978
TI  - Palliative treatment of malignant esophageal stenosis: the role of self-expanding
      stent endoscopic implantation.
AB  - Endoscopic tube implantations were carried out in 40 patients with malignant
      stenosis of the esophagus and gastric cardia using self-expanding metallic
      stents. The indications for endoscopic intubation were the advanced stage of the
      tumor in 27 cases and risk factors that made resection inadvisable in 13 cases.
      In three patients, it proved impossible to implant a stent endoscopically because
      we were not able to pass the guide wire through the stenosis, whereas correct
      stent placement was achieved in 37 cases. Functional results were good in 33
      patients, but four patients did not show any improvement of symptoms.
      Complications occurred in nine patients (24.3%): two bleedings, three neoplastic
      obstructions, one food obstruction, and three distal dislodgements of the
      prosthesis were observed, but could be readily corrected. No deaths occurred. The
      median survival time was 151 days (range 25-545 days). This study suggests that
      endoscopic placement of metallic self-expanding stents is safe and is to be
      preferred to plastic stents for easier implantation and lower morbidity.

PMID- 11284979
TI  - Synchronous esophageal and renal cell carcinoma.
AB  - Multiple cancer associated with esophageal cancer is not uncommon; however,
      synchronous esophageal and renal cell carcinoma is very rare. Only three cases
      have been reported to date, and one of these patients was treated in our
      institution. We have since successfully treated another patient. Here, we report
      the two cases treated in our institution. In the first case, esophagectomy,
      nephrectomy, and reconstruction using a gastric tube were carried out in one
      stage. Post-operative renal function was temporarily impaired by the
      complications of anastomotic leakage and pyothorax but no hemodialysis was
      needed. In the second case, as the patient had undergone distal gastrectomy
      because of gastric cancer, we chose a two-stage operation, i.e. esophagectomy and
      nephrectomy as the first stage, followed by reconstruction using a colon
      substitute after 4 weeks, resulting in only slight renal dysfunction. Patients 1
      and 2 are alive and well 7 years and 2 years after the operations respectively.

PMID- 11284980
TI  - Black esophagus: a view in the dark.
AB  - A 73-year-old man had a low anterior resection for a villous adenoma in the
      rectosigmoid. On the 4th day after surgery, he suddenly developed severe
      interscapular pain. Aortic dissection was ruled out, but endoscopy showed black
      mucosa of the entire esophagus. With conservative treatment, including proton
      pump inhibition, he recovered completely. We hypothesize that a transient gastric
      outlet obstruction and massive gastroesophageal reflux played a significant role
      in the etiology of this rare and alarming, but, in this case, completely
      reversible, syndrome.

PMID- 11284981
TI  - Quality-of-life study on four patients who underwent esophageal resection and
      delayed reconstruction for Boerhaave's syndrome.
AB  - Boerhaave's syndrome is the condition of spontaneous rupture of the esophagus as
      a consequence of the strain of emesis with or without predisposing esophageal
      disease. It is a condition with high mortality. We describe four patients who
      underwent a transthoracic esophagectomy to remove the rupture of the
      intrathoracic esophagus, closure of the esophageal gastric junction, fashioning
      of a feeding gastrostomy, and formation of a left cervical esophagostomy. Three
      patients underwent reconstruction with subcutaneous colon. We suggest that this
      method of management may be considered where primary repair is impossible in
      those patients too ill for prolonged reconstruction or as a salvage procedure
      where other methods have failed. The poor quality of life after esophagectomy is
      improved by reconstruction. Other surgical options include covering the repaired
      opening with a circumferential wrap of pleura, chest wall muscle, or omentum or
      closing the repair around a T-tube of large caliber. Esophageal exclusion using
      absorbable staples is another approach.

PMID- 11284982
TI  - Sarcoidosis and giant midesophageal diverticulum.
AB  - Traction diverticula of the midesophagus result from granulomatous inflammation
      of mediastinal lymph nodes. Tuberculosis and histoplasmosis are known etiologies
      of this condition. To the best of our knowledge, this is the first report of a
      traction diverticulum caused by sarcoidosis.

PMID- 11284983
TI  - Primary malignant melanoma of the esophagus.
AB  - is a rare disease, with only 200 cases being reported since this condition became
      an established clinical entity in 1963. This tumor, which accounts for only 0.1
      0.2% of all esophageal neoplasms, is typically aggressive and disseminates early
      via the bloodstream and lymphatics, with only some 30% of patients surviving > 1
      year after diagnosis. Management of patients with esophageal melanomata is
      unsatisfactory, as most tumors are advanced at diagnosis, and therapeutic options
      are limited by inaccessibility and early dissemination of the neoplasms. Poor
      survival rates reflect the inoperability of many tumors and the ineffectiveness
      of radiation and chemotherapy in eradicating advanced tumors and metastases. We
      present two patients with primary melanoma of the esophagus and discuss the
      treatment options currently available.

PMID- 11284984
TI  - Fibrovascular esophageal polyp as a diagnostic challenge.
AB  - Fibrovascular polyps are rare benign esophageal tumors that usually arise from
      the proximal third of the esophagus. We present the case of a 48-year-old man
      with a history of dysphagia and 7-kg weight loss over a period of 2 months. A
      barium swallow showed a distended esophagus with a tumor extending from the upper
      esophageal sphincter to the cardia. On a thoracic computed tomographic scan, a
      homogeneous intramural mass with a density of 22 Hounsfield units was seen, which
      extended throughout the entire esophagus. Fiberoptic endoscopy confirmed the
      presence an intramural tumor beginning at the upper esophageal sphincter and
      reaching to the cardia. The tumor was completely covered with mucosa, except for
      an ulcerated area at its distal end, which herniated into the stomach. On
      endoscopic ultrasound, the tumor appeared to grow submucosally and to respect the
      muscularis propria. Endoscopic biopsies from the ulcerated distal aspect of the
      tumor suggested a leiomyoma. None of the imaging modalities used revealed
      evidence of a polyp or intraluminal esophageal tumor. Rather, a potentially
      malignant extensive intramural tumor was suspected, and an esophagectomy was
      performed. Only at the time of removal of the specimen did it become evident that
      the tumor mass was located intraluminally with a pedicle in the region of the
      upper esophageal sphincter. The final pathological diagnosis was a giant
      fibrovascular polyp of the esophagus.

PMID- 11284985
TI  - Ischemic spinal cord syndrome after transthoracic esophagectomy: two cases of a
      rare neurologic complication.
AB  - Anterior spinal artery syndrome (ASAS) is a rare complication after surgery of
      the thoracic or abdominal aorta. The sulco commissuralis syndrome represents a
      partial or incomplete ASAS. We report two cases of ischemic spinal cord syndromes
      after transthoracic esophagectomy. This represents a prevalence of this syndrome
      of 0.2% in more than 1000 consecutive esophagectomies performed at our
      institution. Patient 1 developed an ASAS on the first day after esophagectomy.
      Patient 2 showed the pathognomonic clinical signs associated with sulco
      commissuralis syndrome after an asymptomatic window. In both patients, the extent
      of the neurologic symptoms initially improved but then remained unchanged for the
      rest of the follow-up of 9 and 12 months. Although the prognosis of neurologic
      syndromes resulting from spinal cord infarction is poor, preoperative tests to
      identify patients at risk appear not to be justified because of the very low
      incidence of these syndromes after esophagectomy and the poor sensitivity and
      specificity of currently available diagnostic modalities. However, the
      possibility of ischemic spinal cord syndrome should be kept in mind when patients
      present with neurologic symptoms after esophagectomy.

PMID- 11284986
TI  - Mouse cytokine gene nucleotide sequence alignments, 2000. Part IV.

PMID- 11284987
TI  - Nomenclature for factors of the HLA System, update October 2000.

PMID- 11284988
TI  - Nomenclature for factors of the HLA System, update November 2000.

PMID- 11284989
TI  - Nomenclature for factors of the HLA System, update December 2000.

PMID- 11284990
TI  - A survey of neuroimaging research in European neurological departments.
AB  - In the international neurological literature, neuroimaging research plays an
      important role. Neuroimaging techniques are also of steadily increasing
      importance for clinical diagnosis and treatment monitoring. Therefore,
      neuroimaging research activities were surveyed by a questionnaire, which was
      completed by 100 neurological centres across Europe. It showed that most groups
      use magnetic resonance imaging (MRI), fMRI, computerized tomography (CT) and
      single photon emission computerized tomography (SPECT). Positron emission
      tomography (PET) and ultrasound are also employed by nearly half of the centres.
      Neuroimaging research involves co-operation amongst typically five to 10
      disciplines. Cerebrovascular disease, dementia, cognitive disorders, epilepsy,
      movement disorders, brain tumours and multiple sclerosis are frequently being
      studied. Many groups rely on small budgets, have few full-time scientists and
      limited access to expensive resources. There is little exchange of scientists
      amongst laboratories. It was felt that funding and co-operation needed
      improvement in order to maintain a high standard in neuroimaging research.

PMID- 11284991
TI  - Prevalence of Alzheimer's type dementia in an elderly Arab population.
AB  - The aim of this study was to estimate the prevalence of dementia of the Alzheimer
      type (DAT) in an Arab Israeli community. Epidemiological studies of dementia have
      rarely been reported in Arab populations. The target population, aged 60 years or
      older, comprised 821 persons (362 males) who, on 1 October 1995, were residents
      of the rural area of Wadi Ara. These persons were examined for symptoms of
      dementia (DSM-IV criteria), using a semistructured questionnaire for collection
      of demographic and medical data. Age, gender, and education-specific prevalence
      rates were calculated for this population and compared to those obtained in other
      studies. DAT was diagnosed in 20.5% of this population. Its prevalence increased
      steeply with age, from 8% among those younger than 70 years to 33% among those
      aged 70-79 and 51% among those 80 years or older. Illiteracy was very common in
      this population, and strongly associated with higher prevalence of DAT (27% vs.
      4%, P < 0.001). DAT was more prevalent among females than males (25% vs. 15%, P <
      0.001). However, illiteracy was also significantly more frequent among women (96%
      vs. 42%, P < 0.001). After correction for illiteracy, the gender difference lost
      statistical significance. Few women smoked, but among men, the prevalence of DAT
      in those who smoked was lower as compared to non-smokers (14% vs. 23%, a non
      significant difference). These results were confirmed by logistic regression
      wherein DAT was included as the dependent variable and age, illiteracy, gender
      and smoking as independent variables (OR=2.8, 2.8, 1.2 and 0.7, respectively; P <
      0.005 for each, except for smoking). Our findings suggest that this population is
      unique because of extremely high rates of dementia. While the results support a
      protective effect of schooling against the development of dementia, other factors
      (e.g. genetic) must be sought to explain this high frequency.

PMID- 11284992
TI  - A prospective, open-label treatment trial to compare the effect of IFN beta-1a
      (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (Copaxone) on the
      relapse rate in relapsing-remitting multiple sclerosis.
AB  - A prospective, non-randomized, open-label treatment trial was performed in
      patients with relapsing-remitting multiple sclerosis (RRMS), with follow up for
      12 months. Our primary objective was to prospectively compare the effect of
      IFNbeta-1a (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (GA,
      Copaxone) on the relapse rate in patients with RRMS. Between August 1996 and
      September 1999, 156 consecutive patients with clinically definite RRMS with a
      Kurtzke scale (EDSS) score of 4 or less were followed for 12 months, from the
      time of initiating therapy or electing to remain untreated. Prior 2-year relapse
      history and available chart information was carefully reviewed at the time of
      enrolment. Thirty-three of 156 elected no treatment (mean age 32.5 years; mean
      EDSS 2.64) at enrolment; 40 elected IFNbeta-1a (mean age 32.4 years; mean EDSS
      2.69), 41 IFNbeta-1b (mean age 32.1 years; mean EDSS 2.56), and 42 chose GA (mean
      age 31.5 years; mean EDSS 2.57). Annual relapse rate based upon the 2 years prior
      to enrolment was 1.08 in the untreated group, 1.20 in the AV group, 1.21 in the
      BE group, and 1.10 in the GA group. There were no statistically significant
      differences among the four groups at enrolment. After 12 months of treatment,
      patients in the untreated groups had a relapse rate of 0.97, whereas patients in
      the IFNbeta-1a, IFNbeta-1b, and GA groups had relapse rate of 0.85, 0.61, and
      0.62, respectively. Compared to the untreated group, reduction in the relapse
      rate was statistically significant only in the GA (P=0.003) and IFNbeta-1b
      (P=0.002) groups, in contrast to the IFNbeta-1a treated patients, who did not
      show a significant reduction (P=0.309). Compared to the untreated patients, mean
      EDSS was significantly reduced only in the GA (P=0.001) and IFNbeta-1b (P=0.01),
      in contrast to IFNbeta-1a treated patients (P=0.51). In this prospective,
      controlled, open-label, non-randomized 12-month study, treatment with only GA and
      IFNbeta-1b significantly reduced the relapse rate compared to untreated patients,
      supporting early treatment in RRMS. Our results are similar to the observations
      made after 12 months of therapy in phase III studies of IFNbeta-1a, IFNbeta-1b,
      and GA. Despite some limitations of the study design, the results provide helpful
      clinical information regarding the relative efficacy of each therapy in mildly
      affected treatment-naive RRMS patients.

PMID- 11284993
TI  - Combined use of sphenoidal electrodes and the dipole localization method for the
      identification of the mesial temporal focus.
AB  - We attempted to sub-classify four cases who show temporal spikes on standard
      scalp electroencephalogram (EEG), using sphenoidal electrodes and the dipole
      localization METHOD: In a case with mesial temporal epilepsy, spikes showed phase
      reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in
      the mesial temporal lobe. In a case with lateral temporal epilepsy, spikes showed
      no phase reversal in a sphenoidal electrode, and the spike dipoles were estimated
      to be in the lateral temporal lobe. In two cases out of four, spikes showed phase
      reversal in sphenoidal electrodes, whilst the dipoles were estimated to be in the
      frontal lobe. Clinical features also suggested a diagnosis of frontal lobe
      epilepsy. In one of the two cases in which frontal lobe epilepsy was suspected,
      ictal dipoles as well as interictal spike dipoles indicated participation of the
      frontal lobe in the genesis of seizures. Nevertheless, only mesial temporal
      lobectomy was performed based on results obtained by invasive subdural
      electrodes. As a result, seizures were not controlled. Although sphenoidal
      electrodes were useful for differentiating between mesial and lateral temporal
      lobe foci, it is advisable to use them in combination with the dipole
      localization method to identify frontal lobe foci.

PMID- 11284994
TI  - Chronic polyneuropathies in Vest-Agder, Norway.
AB  - Epidemiological data on chronic polyneuropathies, especially inflammatory types,
      is limited. The purpose of this study was to examine the spectrum of causes and
      estimated prevalence of various polyneuropathy types in Vest-Agder, and to
      examine the clinical features of the Vest-Agder population of chronic
      inflammatory demyelinating polyneuropathy (CIDP). In Vest-Agder county
      (population of 155 464), polyneuropathy patients are registered in a database and
      followed prospectively. We did a measure of the database on October 31 1999. A
      total of 192 patients were registered. The prevalence for chronic inflammatory
      demyelinating polyneuropathy (CIDP) was 7.7 per 100 000 population. The course
      was relapsing in five of fifteen patients, progressive in four patients and
      slowly progressive in six of fifteen patients. Two of the fifteen patients had
      pure sensory symptoms. The mean Rankin disability score was 3.4 at maximal
      deficit and 2.1 at last follow-up. The prevalence of paraproteinemic
      polyneuropathy was 5.1 per 100 000 population. None of the patients with
      paraproteinemic polyneuropathy were worse than slightly disabled (disability
      score < or = 2). The prevalences for other polyneuropathies were as follows:
      polyneuropathy and RA, 1.3; polyneuropathy and Sjogren's syndrome or sicca
      complex, 4.5 (polyneuropathy was the presenting symptom in five of seven
      patients); sarcoidosis 1.9; polyneuropathy and chronic Lyme, 0.6; paraneoplastic
      polyneuropathy, 1.9; diabetic polyneuropathy 23.2; vitamin deficiency, 5.1;
      alcoholic and toxic polyneuropathy, 19.9; hereditary polyneuropathy, 14.8.
      Cryptogenic polyneuropathies made up 26% of all polyneuropathies. The mean
      disability score was 2.0 (SD 1.1). In conclusion, prevalence of CIDP was
      significantly higher than previously reported, and the prognosis was good in the
      majority of patients. Patients with paraproteinemic polyneuropathy were not
      severely disabled. Polyneuropathy was the presenting symptom in the majority of
      patients with Sjogren's syndrome or sicca complex.

PMID- 11284995
TI  - Sporadic ALS associated with the D90A Cu,Zn superoxide dismutase mutation in
      Russia.
AB  - Twenty blood samples from Russian patients (Moscow) with idiopathic motor neurone
      disease were analysed for mutations in the Cu,Zn superoxide dismutase (Cu,Zn SOD)
      gene. Two patients (10%) with the amyotrophic lateral sclerosis (ALS) form of the
      disease were found to have a disease-related mutation. One patient appears to
      have autosomal recessive adult-onset ALS associated with homozygosity for D90A
      and presents the characteristic phenotype of very slowly ascending paresis with
      both lower and upper motor neurone signs. Another patient, heterozygous for D90A,
      presents ALS with lumbar onset and rapid progression. This is the first report of
      a Cu,Zn SOD mutation in ALS in Russia.

PMID- 11284996
TI  - Calcitonin gene-related peptide levels during nitric oxide-induced headache in
      patients with chronic tension-type headache.
AB  - It has been proposed that nitric oxide (NO) induced headache in primary headaches
      may be associated with release of calcitonin gene-related peptide (CGRP). In the
      present study we aimed to investigate plasma levels of CGRP during headache
      induced by the NO donor glyceryl trinitrate (GTN) in 16 patients with chronic
      tension-type headache and 16 healthy controls. The subjects were randomly
      allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min on two headache
      free days. Blood samples were collected at baseline, 10, 20 and 60 min after
      start of infusion. Both patients and controls developed significantly stronger
      immediate headache on the GTN day than on the placebo day and the headache was
      significantly more pronounced in patients than in controls. There was no
      difference between the area under the CGRP curve (AUCCGRP) on GTN vs. placebo day
      in either patients (P=0.65) or controls (P=0.48). The AUCCGRP recorded on the GTN
      day did not differ between patients and controls (P=0.36). Both in patients and
      controls, CGRP levels changed significantly over time, on both the GTN and
      placebo days (P < 0.05). The present study indicates that NO-induced immediate
      headache is not associated with release of CGRP.

PMID- 11284997
TI  - Interest in genetic testing in pallido-ponto-nigral degeneration (PPND): a family
      with frontotemporal dementia with Parkinsonism linked to chromosome 17.
AB  - The specific mutation on the tau gene responsible for a neurodegenerative disease
      known as pallido-ponto-nigral degeneration (PPND) was recently located. PPND
      family members are at risk for an autosomal dominant form of frontotemporal
      dementia with Parkinsonism linked to chromosome 17 (FTDP-17). This study
      investigated whether individuals in this family would consider presymptomatic
      genetic testing. Surveys were sent to 66 at-risk individuals in the family;
      replies were received from 20 (30%). Family members were asked if they would
      consider having testing now or in the future, and to indicate their reasons for
      and against proceeding with testing. Fifty per cent (n=10) of those who were at
      risk and who responded indicated they would consider testing now, and 55% (n=11)
      would think about it in the future. The most frequently cited reasons to proceed
      with testing were to 'collaborate with research' (70%) and to 'know if my
      children are at risk' (45%). The most frequently cited reason not to pursue
      testing was 'I can enjoy my life more fully by not knowing' (50%). Results
      suggest that interest in determining whether they will manifest PPND is generally
      low among at-risk members of this family, despite wide support and participation
      in other research studies.

PMID- 11284998
TI  - Dream recall frequency and sleep quality of patients with restless legs syndrome.
AB  - The present study investigated the dream recall frequency and the pattern of
      influencing factors of patients with restless legs syndrome in comparison with
      healthy controls. The patients' dream recall frequency did not differ from that
      of healthy controls. Dream recall, however, was negatively associated with the
      number of periodic leg movements with arousal (PLMAI). Subjective estimates of
      sleep quality or feeling of being refreshed in the morning, on the other hand,
      did not correlate with the PLMAI index. Whereas subjective sleep parameters were
      related to dream recall frequency in healthy controls, no substantial
      relationships were found in the patient group, except for the positive
      correlation between sleep latency and dream recall frequency. The results of the
      present study can not be interpreted as clear evidence for the arousal-retrieval
      model of dream recall; it seems plausible that other factors, e.g. the functional
      state of the brain, are of importance in explaining dream recall in this patient
      group.

PMID- 11284999
TI  - Musicogenic epilepsy with ictal single photon emission computed tomography
      (SPECT): could these cases contribute to our knowledge of music processing?
AB  - Musicogenic epilepsy has a strong correlation with the temporal lobe with a right
      sided preponderance. We report the case of a 48-year-old woman whose seizures
      began at the age of 32 years. Her prenatal, natal and childhood histories were
      unremarkable and her family history was negative for epilepsy. She had typical
      complex partial seizures with chewing automatisms. Cranial computed tomography,
      magnetic resonance imaging (MRI) and interictal SPECT showed no abnormality.
      Interictal EEG showed paroxysmal bitemporal sharp wave discharges predominant on
      the right side. Ictal EEG showed a combination of high voltage sharp and slow
      sharp waves and spikes that originated from the right temporal leads and then
      became generalized. Ictal activity on EEG started 4-5 min after the music
      stimulus. For the ictal SPECT study, i.v. injection of 20 mCi of HMPAO was
      administered approximately 30 s after the ictal activity started. Ictal SPECT
      demonstrated a right anterior and mesial temporal hyperperfusion. These results
      seem to support the dominant role of the right temporal lobe and the possible
      relation of mesial temporal structures to the affective content of music in
      musicogenic epilepsy.

PMID- 11285000
TI  - Calculi and memory.
AB  - We describe a case of transient global amnesia related to symptomatic renal
      stones. Transient global amnesia has been related to intense emotional or painful
      experiences, such as sexual intercourse, cold water bathing and trigeminal
      stimulation. Renal stones may be at the origin of a painful experience and thus
      may induce transient global amnesia.

PMID- 11285001
TI  - Palatal palsy in dermatomyositis.

PMID- 11285002
TI  - Autoimmune hyperthyroidism in multiple sclerosis under treatment with glatiramer
      acetate--a case report.

PMID- 11285003
TI  - Dopaminergic control of synaptic plasticity in the dorsal striatum.
AB  - Cortical glutamatergic and nigral dopaminergic afferents impinge on projection
      spiny neurons of the striatum, providing the most significant inputs to this
      structure. Isolated activation of glutamate or dopamine (DA) receptors produces
      short-term effects on striatal neurons, whereas the combined stimulation of both
      glutamate and DA receptors is able to induce long-lasting modifications of
      synaptic excitability. Repetitive stimulation of corticostriatal fibres causes a
      massive release of both glutamate and DA in the striatum and, depending on the
      glutamate receptor subtype preferentially activated, produces either long-term
      depression (LTD) or long-term potentiation (LTP) of excitatory synaptic
      transmission. D1-like and D2-like DA receptors interact synergistically to allow
      LTD formation, while they operate in opposition during the induction phase of
      LTP. Corticostriatal synaptic plasticity is severely impaired after chronic DA
      denervation and requires the stimulation of DARPP-32, a small protein expressed
      in dopaminoceptive spiny neurons which acts as a potent inhibitor of protein
      phosphatase-1. In addition, the formation of LTD and LTP requires the activation
      of PKG and PKA, respectively, in striatal projection neurons. These kinases
      appear to be stimulated by the activation of D1-like receptors in distinct
      neuronal populations.

PMID- 11285004
TI  - Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and
      skeletal muscle.
AB  - We have investigated the impact of neuromuscular activity on the expression of
      neurotrophins in the lumbar spinal cord region and innervating skeletal muscle of
      adult rats. Rats were exercised on a treadmill for 1 day or 5 consecutive days
      and euthanized at 0, 2 or 6 h after the last bout of exercise. By Day 1, there
      was no clear evidence of an increase in brain-derived neurotrophic factor (BDNF)
      mRNA in the spinal cord or the soleus muscle. By Day 5, there was a significant
      increase in BDNF mRNA in the spinal cord at 2 h post-training, and the soleus
      muscle showed a robust increase between 0 and 6 h post-training. Immunoassays
      showed significant increases in BDNF protein in the soleus muscle by training Day
      5. Immunohistochemical analyses showed elevated BDNF levels in motoneuron cell
      bodies and axons in the ventral horn. Neurotrophin-3 (NT-3) mRNA was measured to
      determine whether selected neurotrophins respond with a selective pattern of
      induction to neuromuscular activity. In the spinal cord, there was a progressive
      post-training decrease in NT-3 mRNA following a single bout of training, while
      there was a significant increase in NT-3 mRNA at 2 h post-training by Day 5. The
      soleus muscle showed a progressive increase in NT-3 mRNA by Days 1 and 5
      following training. These results show that neuromuscular activity has specific
      effects on the BDNF and NT-3 systems, and that repetitive exercise affects the
      magnitude and stability of these responses.

PMID- 11285005
TI  - Immunophilin ligands can prevent progressive dopaminergic degeneration in animal
      models of Parkinson's disease.
AB  - Slowing or halting the progressive dopaminergic (DA) degeneration in Parkinson's
      disease (PD) would delay the onset and development of motor symptoms, prolong the
      efficacy of pharmacotherapies and decrease drug-induced side-effects. We tested
      the potential of two orally administered novel immunophilin ligands to protect
      against DA degeneration in two animal models of PD. First, in an MPTP (N-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine) mouse model, we compared an immunophilin
      ligand (V-10,367) documented to bind the immunophilin FKBP12 with V-13,661, which
      does not bind FKBP12. Both molecules could prevent the loss of striatal DA
      innervation in a dose-dependent fashion during 10 days of oral administration.
      Second, to determine whether an immunophilin ligand can protect against
      progressive and slow DA degeneration typical of PD, an intrastriatal 6
      hydroxydopamine-infusion rat model was utilized. Oral treatment with the FKBP12
      binding immunophilin ligand began on the day of lesion and continued for 21 days.
      At this time point, post mortem analyses revealed that the treatment had
      prevented the progressive loss of DA innervation within the striatum and loss of
      DA neurons within the substantia nigra, related to functional outcome as measured
      by rotational behaviour. Notably, DA fibres extending into the area of striatal
      DA denervation were observed only in rats treated with the immunophilin ligand,
      indicating neuroprotection or sprouting of spared DA fibres. This is the first
      demonstration that immunophilin ligands can prevent a slow and progressive DA
      axonal degeneration and neuronal death in vivo. The effects of orally
      administered structurally related immunophilin ligands in acute and progressive
      models of DA degeneration are consistent with the idea that these compounds may
      have therapeutic value in PD.

PMID- 11285006
TI  - Noradrenergic modulation of calcium currents and synaptic transmission in the
      olfactory bulb of Xenopus laevis tadpoles.
AB  - Norepinephrine (NE) has various modulatory roles in both the peripheral and the
      central nervous systems. Here we investigate the function of the locus coeruleus
      efferent fibres in the olfactory bulb of Xenopus laevis tadpoles. In order to
      distinguish unambiguously between mitral cells and granule cells of the main
      olfactory bulb and the accessory olfactory bulb, we used a slice preparation. The
      two neuron types were distinguished on the basis of their location in the slice,
      their typical branching pattern and by electrophysiological criteria. At NE
      concentrations lower than 5 microM there was only one effect of NE upon voltage
      gated conductances; NE blocked a high-voltage-activated Ca(2+)-current in mitral
      cells of both the main and the accessory olfactory bulbs. No such effect was
      observed in granule cells. The effect of NE upon mitral cell Ca(2+)-currents was
      mimicked by the alpha(2)-receptor agonists clonidine and alpha-methyl-NE. As a
      second effect, NE or clonidine blocked spontaneous synaptic activity in granule
      cells of both the main and the accessory olfactory bulbs. NE or clonidine also
      blocked the spontaneous synaptic activity in mitral cells of either olfactory
      bulb. The amplitude of glutamate-induced currents in granule cells was modulated
      neither by clonidine nor by alpha-methyl-NE. Taken together, the main effect of
      the noradrenergic, presynaptic, alpha(2)-receptor-mediated block of Ca(2)+
      currents in mitral cells appeared to be a wide-spread disinhibition of mitral
      cells in the accessory olfactory bulb as well as in the main olfactory bulb.

PMID- 11285007
TI  - Bacterial endotoxin sensitizes the immature brain to hypoxic--ischaemic injury.
AB  - Epidemiological studies show a markedly increased risk of cerebral palsy
      following the combined exposure of infection and birth asphyxia. However, the
      underlying mechanisms of this increased vulnerability remain unclear. We have
      examined the effects of a low dose of bacterial endotoxin on hypoxic--ischaemic
      injury in the immature brain of rats. Bacterial endotoxin (lipopolysaccharide 0.3
      mg/kg) was administered to 7-day-old rats 4 h prior to unilateral hypoxia-
      ischaemia and the neurological outcome was determined 3 days later. Rectal
      temperature and cerebral blood flow was measured during the study and the
      expression of CD14 and toll-like receptor-4 mRNA in the brain was examined. We
      found that a low dose of endotoxin dramatically sensitizes the immature brain to
      injury and induces cerebral infarction in response to short periods of hypoxia-
      ischaemia that by themselves caused no or little injury. This effect could not be
      explained by a reduction in cerebral blood flow or hyperthermia. In association
      with the sensitization of injury we found an altered expression of CD14 mRNA and
      toll-like receptor-4 mRNA in the brain. These results suggest that the innate
      immune system may be involved in the vulnerability of the immature brain
      following the combination of infection and hypoxia--ischaemia.

PMID- 11285008
TI  - VP-RBP, a protein enriched in brain tissue, specifically interacts with the
      dendritic localizer sequence of rat vasopressin mRNA.
AB  - The concept of mRNA localization suggests that this process is mediated by
      sequences residing in the transcript to which proteins specifically bind and
      ultimately deliver the mRNA along cytoskeletal elements to specific intracellular
      destinations. The mRNA encoding the vasopressin (VP) precursor protein is
      localized to the nerve cell processes both in hypothalamic magnocellular neurons
      and in primary cultured neurons derived from embryonic rat superior cervical
      ganglia microinjected with a corresponding eukaryotic expression vector. The last
      395 nucleotides of the VP mRNA encompassing part of the coding region, as well as
      the complete 3'-untranslated region, are sufficient to confer dendritic targeting
      to a normally nonlocalized reporter transcript. Here we report that, by employing
      in vitro crosslinking analyses with rat brain proteins and radiolabelled VP
      transcripts, an RNA-binding protein specifically interacts with the dendritic
      localizer sequence of the VP mRNA. This protein is enriched in nerve cell
      tissues. Peripheral tissues and various cell lines contain only low amounts of
      the binding activity. It therefore represents a candidate protein that may be
      involved in any aspect related to subcellular VP mRNA sorting in nerve cells,
      including transport and anchoring of the mRNA and possibly its translational
      control.

PMID- 11285009
TI  - Alterations in dystrophin and utrophin expression parallel the reorganization of
      GABAergic synapses in a mouse model of temporal lobe epilepsy.
AB  - Dystrophin and its autosomal homologue utrophin are coexpressed in muscle cells,
      and utrophin is functionally able to replace dystrophin in models of Duchenne
      muscular dystrophy. In brain, the two proteins are expressed differentially,
      suggesting distinct functional roles. Dystrophin is associated with postsynaptic
      GABA(A) receptors in hippocampus, cortex and cerebellum, whereas utrophin is
      present extrasynaptically, notably in large brainstem neurons. Here, the
      regulation of dystrophin and utrophin was investigated in a model of temporal
      lobe epilepsy. Adult mice were injected unilaterally with kainic acid into the
      dorsal hippocampus to induce loss of pyramidal cells and hypertrophy of dentate
      gyrus (DG) granule cells, as described (Suzuki, F., Junier, M.P., Guilhem, D.,
      Sorensen, J.C. & Onteniente, B. (1995) Neuroscience, 64, 665--674.). These
      morphological changes were associated with an increase in postsynaptic GABA(A)
      receptors in the ipsilateral DG, as demonstrated by a parallel increase in
      punctate immunoreactivity to GABA(A)-receptor alpha 2 subunit, gephyrin and
      dystrophin in the molecular layer. Thus, both dystrophin and gephyrin were
      involved in postsynaptic clustering of GABA(A) receptors. A transient induction
      of utrophin was seen at the onset of degeneration in CA1 and CA3 pyramidal cells
      and in the hilus. Most strikingly, however, utrophin immunoreactivity appeared in
      the granule cell layer of the DG and became very strong in hypertrophic granule
      cells 1--2 months post-kainate treatment. These results suggest that utrophin
      provides structural support of neuronal membranes, whereas dystrophin is a
      component of GABAergic synapses.

PMID- 11285010
TI  - Effects of amyloid peptides on cell viability and expression of neuropeptides in
      cultured rat dorsal root ganglion neurons: a role for free radicals and protein
      kinase C.
AB  - Chronic pain caused by nerve injury and inflammation is more common in the
      elderly. However, mechanisms underlying this phenomenon are unclear. Higher
      sensitivity of sensory neurons to free radicals has been suggested as one
      possibility. The production of free radicals can be induced by various agents,
      including the highly toxic protein beta-amyloid (A beta), which is found in
      higher amounts in the brains of Alzheimer's Disease patients. In dorsal root
      ganglion (DRG) cultures exposed to A beta, we examined cellular toxicity and
      peptide expression, in particular calcitonin gene-related peptide (CGRP), a
      peptide which is abundantly expressed by nociceptive afferents and is known to be
      involved in pain processes. Exposure of cultured rat DRG neurons to A beta(25-
      35) or A beta(1--40) (10 or 20 microM for 24--96 h) increased trypan blue-stained
      cells in a concentration- and time-dependent manner, thus, indicating cellular
      toxicity. These treatments also increased the number of CGRP immunoreactive (IR)
      neurons while decreasing the number of neuropeptide Y- and galanin-IR neurons.
      The free radical scavenger, superoxide dismutase, attenuated both the toxicity
      and neuropeptide changes induced by A beta, thus, suggesting that oxidative
      stress probably contributes to these effects. Exposure of cultured DRG neurons to
      A beta also increased the number of protein kinase C alpha (PKC alpha)-IR
      neurons. The PKC inhibitors, chelerythrine chloride and Go6976, significantly
      augmented A beta-induced cellular toxicity while attenuating the increases in
      CGRP-and PKC alpha-IR cells, supporting the notion of a protective role for PKC
      in A beta insults. These in vitro data suggest that A beta peptides may, in
      addition to causing neurotoxicity, regulate neuropeptide expression in primary
      afferents. This finding could be relevant to the higher incidence of neuropathic
      pain that occurs with ageing.

PMID- 11285011
TI  - Correlation between electrophysiological and morphological characteristics during
      maturation of rat supraoptic neurons.
AB  - The neurohypophysial peptides oxytocin (OT) and vasopressin (AVP) are well known
      for their role in reproductive functions and fluid balance regulation,
      respectively. During development, these peptides are thought to act as trophic
      factors on both peripheral and central structures. However, despite this early
      developmental function, the maturation of their secreting neurons remains poorly
      investigated. In this study, we have characterized the electrical and
      morphological characteristics displayed by OT and AVP supraoptic (SO) neurons
      between embryonic day 21 and postnatal day 20. Transient changes in passive
      membrane properties, correlated with a transient increase in the dendritic
      arborization, were observed at the beginning of the second postnatal week (PW2).
      The action potential matured mostly during PW1 and its threshold progressively
      hyperpolarized in parallel with the resting membrane potential. During PW1, SO
      neurons displayed unique characteristics with a low-threshold Ca(2+)-dependent
      depolarizing potential and a prominent hyperpolarization-activated current (I(h)
      ). This latter is involved in a depolarizing sag during hyperpolarization and an
      after hyperpolarizing potential following a depolarization. During this period,
      maintaining E(Cl) unchanged by the use of gramicidin-perforated patch recordings
      revealed excitatory GABAergic potentials, that became inhibitory during PW2,
      whilst glutamatergic potential appeared. The electrical activity was very erratic
      in young neurons and progressively differentiated in the typical firing observed
      in mature neurons (tonic and phasic for OT and AVP neurons, respectively) during
      PW2--3. These results show that the development of electrical properties of SO
      neurons is correlated with the maturation of their dendritic arborization.

PMID- 11285012
TI  - Cajal-Retzius cells in early postnatal mouse cortex selectively express
      functional metabotropic glutamate receptors.
AB  - Glutamate receptors have been linked to the regulation of several developmental
      events in the CNS. By using cortical slices of early postnatal mice, we show that
      in layer I cells, glutamate produces intracellular calcium ([Ca(2+)](i))
      elevations mediated by ionotropic and metabotropic glutamate receptors (mGluRs).
      The contribution of mGluRs to these responses was demonstrated by application of
      tACPD, an agonist to groups I and II mGluRs, which evoked [Ca(2+)](i) increases
      that could be reversibly blocked by MCPG, an antagonist to groups I and II
      mGluRs. In the absence of extracellular Ca(2+), repetitive applications of tACPD
      or quisqualate, an agonist to group I mGluRs, elicited decreasing [Ca(2+)](i)
      responses that were restored by refilling a thapsigargin-sensitive Ca(2+) store.
      The use of specific group I mGluR agonists CHPG and DHPG indicated that the
      functional mGluR in layer I was of the mGluR1 subtype. Subtype specific
      antibodies confirmed the presence of mGlur1 alpha, but not mGluR5, in Cajal
      Retzius (Reelin-immunoreactive) neurons.

PMID- 11285013
TI  - Central monoamine and plasma corticosterone changes induced by a bacterial
      endotoxin: sensitization and cross-sensitization effects.
AB  - Low doses of lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta), or exposure to a stressor (restraint) increased
      plasma corticosterone levels. In animals pretreated with lipopolysaccharide, a
      marked sensitization of the corticosterone response was evident upon subsequent
      exposure to lipopolysaccharide, TNF-alpha, or restraint, 1 day later. As well,
      the sickness-inducing effects of lipopolysaccharide, TNF-alpha and IL-1 beta were
      markedly increased in mice pretreated with lipopolysaccharide. The sensitization
      effects were marked when the second treatment was administered 1 day after
      lipopolysaccharide administration, but not when a 28-day interval elapsed. In a
      second experiment, TNF-alpha influenced monoamine functioning in the
      paraventricular nucleus of the hypothalamus and within extrahypothalamic regions,
      including the central amygdala, locus coeruleus, prefrontal cortex. Moreover,
      serotonin activity within the central amygdala, as well as dopamine activity
      within the prefrontal cortex, were subject to a sensitization effect in animals
      pretreated with lipopolysaccharide 1 day earlier. Macrophage depletion by a
      suspension of clodronate liposomes attenuated the plasma corticosterone changes
      induced by TNF-alpha, but did not affect the sensitization. In contrast, the
      acute effects of TNF-alpha on central neurotransmitters were unaffected by the
      liposome suspension, but this treatment prevented the sensitization. These data
      may be relevant to clinical situations in which individuals exposed to bacterial
      infections may be rendered more susceptible to the behavioural and neurochemical
      effects of subsequently encountered stressors and immunological challenges.

PMID- 11285014
TI  - Emergence of axons from distal dendrites of adult mammalian neurons following a
      permanent axotomy.
AB  - The distinctive features of axons and dendrites divide most neurons into two
      compartments. This polarity is fundamental to the ability of most neurons to
      integrate synaptic signals and transmit action potentials. It is not known,
      however, if the polarity of neurons in the adult mammalian nervous system is
      fixed or plastic. Following axotomy, some distal dendrites of neck motoneurons in
      the adult cat give rise to unusual processes that, at a light microscopic level,
      resemble axons (Rose, P.K. & Odlozinski, M., J. Comp. Neurol., 1998, 390, 392).
      The goal of the present experiments was to characterize these unusual processes
      using well-established ultrastructural and molecular criteria that differentiate
      dendrites and axons. These processes were immunoreactive for growth-associated
      protein-43 (GAP-43), a protein that is normally confined to axons. In contrast,
      immunoreactivity for a protein that is widely used as a marker for dendrites,
      microtubule-associated protein (MAP)-2a/b, could not be detected in the unusual
      distal arborizations. At the electron microscopic level, unusual distal processes
      contained dense collections of neurofilaments and were frequently myelinated.
      These molecular and structural characteristics are typical of axons and suggest
      that the polarity of adult neurons in the mammalian nervous system can be
      disrupted by axotomy. If this transformation in neuronal polarity is common to
      other types of neurons, axon-like processes emerging from distal dendrites may
      represent a mechanism for replacing connections lost due to injury.
      Alternatively, the connections formed by these axons may be aberrant and
      therefore maladaptive.

PMID- 11285015
TI  - Activation of frontoparietal cortices during memorized triple-step sequences of
      saccadic eye movements: an fMRI study.
AB  - To determine the cortical areas controlling memory-guided sequences of saccadic
      eye movements, we performed functional magnetic resonance imaging (fMRI) in six
      healthy adults. Subjects had to perform a memorized sequence of three saccades in
      darkness, after a triple-step stimulus of successively flashed laser targets. To
      assess the differential contribution of saccadic subfunctions, we applied several
      control conditions, such as central fixation with or without triple-step visual
      stimulation, self-paced saccades in darkness, visually guided saccades and single
      memory-guided saccades. Triple-step saccades strongly activated the regions of
      the frontal eye fields, the adjacent ventral premotor cortex, the supplementary
      eye fields, the anterior cingulate cortex and several posterior parietal foci in
      the superior parietal lobule, the precuneus, and the middle and posterior portion
      of the intraparietal sulcus, the probable location of the human parietal eye
      field. Comparison with the control conditions showed that the right intraparietal
      sulcus and parts of the frontal and supplementary eye fields are more involved in
      the execution of triple-step saccades than in the other saccade tasks. In
      accordance with evidence from clinical lesion studies, we propose that the
      supplementary eye field essentially controls the triggering of memorized saccadic
      sequences, whereas activation near the middle portion of the right intraparietal
      sulcus appears to reflect the necessary spatial computations, including the use
      of extraretinal information (efference copy) about a saccadic eye displacement
      for updating the spatial representation of the second or third target of the
      triple-step sequence.

PMID- 11285016
TI  - Restricted-feeding-induced anticipatory activity rhythm is associated with a
      phase-shift of the expression of mPer1 and mPer2 mRNA in the cerebral cortex and
      hippocampus but not in the suprachiasmatic nucleus of mice.
AB  - Daily restricted feeding (RF) can produce food-entrainable oscillations in both
      intact and suprachiasmatic nucleus (SCN)-lesioned animals. Thus, there are two
      circadian rhythms, one of which is SCN-dependent and the other SCN-independent.
      Recently, it has been established that several mouse clock genes, such as mPer1,
      mPer2 and mPer3 are expressed in the SCN and other brain tissues. Although the
      role of mPer genes expressed in the SCN has recently been evaluated in the SCN
      dependent rhythm, their function in the SCN-independent rhythm is still poorly
      understood. In order to understand the role of these genes in SCN-independent
      rhythm, we examined the expression pattern of mPer1 and mPer2 mRNA in each brain
      area of mice under RF. Mice were allowed access to food for 4 h during either the
      daytime under a light-dark cycle or the subjective daytime under constant dark.
      After 6 days of scheduled RF, the night-time or subjective night-time peak of
      mPer mRNA changed to a daytime peak in the cerebral cortex and hippocampus, with
      moderate expression in the striatum, pyriform cortex and paraventricular nucleus,
      and no expression in the SCN. The daytime peak in the cerebral cortex returned to
      a night-time peak after the release of RF to a free-feeding schedule. Although
      the basal rhythm of mPer expression disappeared in SCN-lesioned mice, RF produced
      mPer mRNA rhythm in the cerebral cortex of these mice. The present results
      provide evidence of an association between food-entrainable oscillations and the
      expression of mPer1 and mPer2 in the cerebral cortex and hippocampus.

PMID- 11285017
TI  - Place fields of rat hippocampal pyramidal cells and spatial learning in the
      watermaze.
AB  - To provide a background for studying place-related activity in hippocampal
      neurons during spatial learning, we compared the activity of hippocampal place
      cells in an annular watermaze and an analogous land-based task. Complex-spike
      cells had robust place correlates in both conditions, and a significant
      proportion of the cells had place fields at the same locations. However, the in
      field firing rates were slightly higher in the wet condition. Elevated firing was
      observed also in an open water task. There was no enhancement when the platform
      location was varied randomly or when there was no platform at all. Second, the
      place fields were under stronger directional modulation during swimming. In the
      annular task, directional sensitivity appeared regardless of whether the animals
      were trained to find a platform or not. There were directionally modulated units
      also in the open watermaze, but the number was smaller than in the corridor.
      Altogether, these observations suggest that place fields in the watermaze are
      largely controlled by the same factors as on dry land, in spite of the
      differences in kinaesthetic and vestibular input. Differences in firing rate and
      directional control may depend on the geometric and cognitive structure of the
      task rather than the medium on which the rats are moving.

PMID- 11285018
TI  - Cortical representation of acoustic motion in the rufous horseshoe bat,
      Rhinolophus rouxi.
AB  - Responses of neurons to apparent auditory motion in the azimuth were recorded in
      three different fields of auditory cortex of the rufous horseshoe bat. Motion was
      simulated using successive stimuli with dynamically changing interaural intensity
      differences presented via earphones. Seventy-one percent of sampled neurons were
      motion-direction-sensitive. Two types of responses could be distinguished. Thirty
      four percent of neurons showed a directional preference exhibiting stronger
      responses to one direction of motion. Fifty-seven percent of neurons responded
      with a shift of spatial receptive field position depending on direction of
      motion. Both effects could occur in the same neuron depending on the parameters
      of apparent motion. Most neurons with contralateral receptive fields exhibited
      directional preference only with motion entering the receptive field from the
      opposite direction. Receptive field shifts were opposite to the direction of
      motion. Specific combinations of spatiotemporal parameters determined the motion
      direction-sensitive responses. Velocity was not encoded as a specific parameter.
      Temporal parameters of motion and azimuth position of the moving sound source
      were differentially encoded by neurons in different fields of auditory cortex.
      Neurons with a directional preference in the dorsal fields can encode motion with
      short interpulse intervals, whereas direction-preferring neurons in the primary
      field can best encode motion with medium interpulse intervals. Furthermore,
      neurons with a directional preference in the dorsal fields are specialized for
      encoding motion in the midfield of azimuth, whereas direction-preferring neurons
      in the primary field can encode motion in lateral positions. The results suggest
      that motion information is differentially processed in different fields of the
      auditory cortex of the rufous horseshoe bat.

PMID- 11285019
TI  - Long-trace interval eyeblink conditioning is impaired in mutant mice lacking the
      NMDA receptor subunit epsilon 1.
AB  - To elucidate the role of the N-methyl-D-aspartate (NMDA) -type glutamate receptor
      subunit epsilon 1 (GluR epsilon 1) in classical eyeblink conditioning, delay and
      trace eyeblink conditioning were investigated in GluR epsilon 1-null mutant mice.
      In delay conditioning and short-trace interval conditioning with a trace interval
      of 250 ms, GluR epsilon 1 mutant mice attained a normal level of the conditioned
      response (CR), although acquisition was a little slower than in wild-type mice.
      In contrast, GluR epsilon 1 mutant mice exhibited severe impairment of the
      attained level of the CR and disturbed temporal pattern of CR expression in trace
      conditioning with a longer trace interval of 500 ms. These findings indicate that
      GluR epsilon 1 is essential for long-trace interval eyeblink conditioning. The
      impairments of the associative learning with a long temporal separation between
      the conditioned and unconditioned stimuli observed in the GluR epsilon 1 mutant
      mice could be attributed to an impairment of hippocampal long-term potentiation
      in this line of mutant mice.

PMID- 11285020
TI  - Impairments in visual discrimination learning and recognition memory produced by
      neurotoxic lesions of rhinal cortex in rhesus monkeys.
AB  - Much work on the cognitive functions of the primate rhinal (i.e. entorhinal plus
      perirhinal) cortex has been based on aspiration lesions of this structure, which
      might disrupt fibres passing nearby and through the rhinal cortex in addition to
      removing the cell bodies of the rhinal cortex itself. To determine whether damage
      limited to the cell bodies of the rhinal cortex is sufficient to impair visual
      learning and memory, four rhesus monkeys (Macaca mulatta) were preoperatively
      trained on a battery of visual learning and memory tasks, including single-pair
      discrimination learning for primary reinforcement, single-pair discrimination
      reversals, concurrent discrimination learning and reversal, and delayed matching
      to-sample. Following acquisition of these tasks and a preoperative performance
      test, ibotenic acid was injected bilaterally into the rhinal cortex, and the
      monkeys were retested. Consistent with the results of studies using aspiration
      lesions, the monkeys were impaired on single-pair discrimination learning as well
      as recognition memory performance postoperatively, although reliable reversal
      learning impairments were not observed. The magnitude of postoperative impairment
      in discrimination learning was not correlated with the magnitude of postoperative
      impairment in recognition memory, suggesting a possible dissociation between
      these functions within the rhinal cortex. The correspondence of behavioural
      deficits following aspiration and neurotoxic lesions of the rhinal cortex
      validates the attribution of various cognitive functions to this structure, based
      on the results of studies with aspiration lesions.

PMID- 11285021
TI  - Visual analysis and image motion in locomoting cats.
AB  - During locomotion, observers see a characteristic pattern of motion referred to
      as an optic flow field. To investigate how they make use of this pattern, we have
      developed a paradigm for testing visual function during locomotion. Foot
      placement was recorded while cats walked down an alley cluttered with a high
      density of small objects; the task was to avoid stepping on any object. In the
      experiments reported here, motion cues were eliminated by the use of low
      frequency strobe lighting. In bright continuous light cats performed with great
      accuracy, and likewise at scotopic light levels. However, in strobe lighting
      their error rates increased more than threefold. This deterioration could not be
      attributed to lower acuity, since the cats' performance remained excellent when
      the light level was reduced well below that afforded by the strobe light. When
      very dim continuous light was combined with low-frequency strobe lighting,
      performance was substantially better than under strobe light alone. We conclude
      that motion-sensitive neurons make a major contribution to visual guidance of
      foot placement during locomotion. When strobe lighting is combined with very dim
      continuous light, even the minimal motion information available in the intervals
      between bright strobe flashes improves performance significantly. Cats were also
      trained to discriminate between complex patterns, and this discrimination was not
      affected by strobe lighting, suggesting that motion-sensitive neurons are not
      critical for this analysis.

PMID- 11285022
TI  - Classical eyeblink conditioning in glutamate receptor subunit delta 2 mutant mice
      is impaired in the delay paradigm but not in the trace paradigm.
AB  - In mice lacking glutamate receptor subunit delta 2 (GluR delta 2(-/-_ mice),
      cerebellar long-term depression (LTD) at the parallel fibre-Purkinje cell
      synapses is disrupted. Unlike the cerebellar LTD-deficient mice previously used
      for eyeblink conditioning, however, the abnormalities of the GluR delta 2(-/-)
      mice are restricted to the cerebellar cortex. In delay eyeblink conditionings
      (interstimulus interval of 252 and 852 ms), in which the conditioned stimulus
      (CS) overlaps temporally with a coterminating unconditioned stimulus (US), GluR
      delta 2(-/-) mice are severely impaired in learning, strongly supporting the
      hypothesis that cerebellar cortical LTD is essential for delay conditioning. In
      the trace paradigm, in which a stimulus-free trace interval of 500 ms intervened
      between the CS and US, GluR delta 2(-/-) mice learned as successfully as wild
      type mice, indicating that cerebellar LTD is not necessary for trace
      conditioning. Thus, the present study has revealed a cerebellar LTD-independent
      learning in eyeblink conditioning.

PMID- 11285023
TI  - Social isolation after a single defeat reduces striatal dopamine transporter
      binding in rats.
AB  - A single social defeat in male rats has long lasting physiological and
      behavioural consequences, which are similar to those seen in depressive patients.
      In addition, the housing conditions after social defeat appear to be crucial for
      the development of depression-like symptoms. Because the dopaminergic system is
      thought to be altered in depressive illness, we investigated the impact of
      individual and group housing on the temporal development of changes of dopamine
      transporter (DAT) binding in male rats after a single social defeat. The number
      of striatal DAT binding sites was reduced in animals that remained isolated after
      being defeated. The isolation length after social defeat amplified this effect,
      indicating a temporal development of the changes on the striatal DAT. In animals
      which returned to the familiar group after social defeat the density of striatal
      DAT binding sites was not affected. We conclude that social isolation after a
      single defeat reduces the number of DAT binding sites. In contrast, a familiar
      environment after a single social defeat appears to prevent the stress-induced
      alterations on the dopaminergic system. This finding suggests that housing
      conditions are critical when investigating the central nervous effects of social
      defeat in male rats.

PMID- 11285024
TI  - Oxygen modulates cell death in the proliferating retina.
AB  - Many factors probably regulate the process of natural cell death during
      development. It is present in both the early undifferentiated retina and later
      following differentiation. Melanin production plays a role in regulating retinal
      development and when it is absent, cell proliferation and death are enhanced.
      Here we examine the effects of hyperoxia on this process, as oxygen has been
      shown to reduce cell death among differentiated photoreceptors late in
      development. However, in this study we examine its effects much earlier in
      pigmented and albino pigmentation phenotypes, when most cells are still actively
      dividing and are not committed to a specific fate. Newborn mice were exposed to
      high oxygen levels for 24 h and then returned to normal air for varying periods
      and their retinae examined. Hyperoxia had a dramatic effect on the number of
      dying cells, reducing them by almost 60% in pigmented animals and by over 80% in
      albinos. Following the return to normal air there was a gradual increase in their
      number over 360 min back to normal levels in pigmented mice; however, in albinos
      there was a complete rebound in levels of cell death within 40 min, reflecting
      the increased metabolic stress present in albino retinae due to their abnormal
      levels of proliferation. These results highlight the important role played by
      oxygen during early natural cell death in the retina and reveal the different
      developmental conditions present in the retinae of the two pigmentation
      phenotypes examined.

PMID- 11285025
TI  - Induction of neonatal sodium channel II and III alpha-isoform mRNAs in neurons
      and microglia after status epilepticus in the rat hippocampus.
AB  - Sodium channels (NaChs) regulate neuronal excitability in both physiological and
      pathological conditions, including epilepsy and are therefore an important target
      for antiepileptic drugs. In the present study, we examined the distribution of
      mRNAs encoding neonatal NaChs II and III alpha-isoforms in control rat
      hippocampus and after electrically-induced status epilepticus (SE), using
      nonradioactive in situ hybridization (ISH). Only weak expression of neonatal NaCh
      II and III mRNAs was observed in control hippocampus. By contrast, increased
      expression of neonatal NaCh II and III mRNAs was observed 4 h after the induction
      of SE in neurons of CA1-CA3 and the dentate granule cell layer. These changes
      were detected only in rats in which SE was successfully induced and persisted,
      although less intense, for up to 3 months, when rats display spontaneous
      seizures. Strong expression of neonatal NaCh alpha-isoforms was observed 1 week
      after SE in microglial cells, as confirmed by double labelling, combining ISH
      with immunocytochemistry for microglia markers. The increased expression of
      neonatal isoforms of the NaCh in both neurons and microglial cells may represent
      a critical mechanism for modulation of neuronal excitability, glial function and
      pharmacological response to antiepileptic drugs in the course of epileptogenesis.

PMID- 11285027
TI  - Cancer care in women: will the practice of the 20th century be relevant in the
      21st? Presidential address. International Gynecological Cancer Society, October
      25, 2000.

PMID- 11285026
TI  - Nicotine regulates 5-HT(1A) receptor gene expression in the cerebral cortex and
      dorsal hippocampus.
AB  - The 5-HT(1A) receptor has previously been shown to be important in mediating the
      behavioural effects of nicotine. It is possible that nicotine administration
      might regulate the levels of 5-HT receptors in limbic and cortical regions, and
      such regulations may underlie adaptive responses to nicotine in the central
      nervous system. The effects of acute and chronic systemic (--)-nicotine
      administration on 5-HT(1A) receptor gene expression were measured by in situ
      hybridization, in the rat cerebral cortex, dorsal hippocampus and lateral septum.
      In the cortex, acute nicotine (0.5 mg/kg i.p.) significantly increased the
      expression of 5-HT(1A) receptor mRNA 2 h and 24 h after injection. Similarly,
      acute nicotine significantly increased 5-HT(1A) receptor mRNA in the dentate
      gyrus (DG), CA3 and CA1 regions of the dorsal hippocampus 2 h and 24 h after
      injection. Acute nicotine was without effect in the lateral septum. Chronic
      nicotine (0.5 mg/kg i.p; twice daily for 7 days) significantly decreased 5-HT(1A)
      receptor mRNA in the cortex 2 h after the final injection, but was without effect
      at 24 h or 72 h. Chronic nicotine caused no changes in 5-HT(1A) mRNA in the
      lateral septum or dorsal hippocampus. These data demonstrate that nicotine
      regulates 5-HT(1A) receptor gene expression in the cortex and hippocampus. The
      rapid regulation of expression of 5-HT(1A) receptor mRNA leads to the hypothesis
      that nicotine-induced 5-HT release may alter the postsynaptic sensitivity to 5
      HT.

PMID- 11285029
TI  - Adenovirus 5 E1a-mediated gene therapy for human ovarian cancer cells in vitro
      and in vivo.
AB  - The aim of this study was to investigate therapeutic efficacy of adenovirus
      mediated E1a gene therapy for ovarian cancer in vitro and in vivo. Recombinant
      replication-deficient adenoviral vectors were prepared by superinfection of 293
      cells, and then purified. The efficacy of the adenovirus vector system to infect
      ovarian cells was tested using different multiplicity of infection (MOI) and
      different times (1-4) of Ad.RSVlacZ. SKOV-3 cells (10(3) per well) were infected
      once with 2 x 10(4) adenovirus. The cells were harvested and counted on different
      days for 7 days to generate the in vitro growth curve. Tumor-bearing mice were
      injected intraperitoneally with ovarian cancer cells and treated by
      intraperitoneal injection of 100 microl (2.5 x 10(8) PFU) viral solution
      containing either replication-deficient Ad.E1a(+); control virus Ad.E1a(-) which
      is the same adenovirus as Ad.E1a(+) except for E1a deletion, or just phosphate
      buffered solution. The transduction efficacy increased with higher MOI and
      reached a plateau at the 20:1 ratio. When Ad.E1a(+) was used to transduce the HER
      2/neu overexpressing human ovarian cancer cell line SKOV-3, tumor cell growth in
      vitro was greatly inhibited by E1a transduction. Also, Ad.E1a+ greatly inhibited
      tumor growth of SKOV-3-bearing mice. Immunohistochemistry analysis indicated that
      Ad.E1a protein was expressed in tumor tissue and expression of HER-2/neu p185
      protein was suppressed. Very strong beta-gal staining was detected in tumors, and
      beta-gal activity in small intestine, lung, heart, stomach, liver, and kidney was
      detected. No beta-gal activity was detected in the tumor and other organs in
      control mice injected with Ad.E1a(-) or PBS. Adenovirus-type 5 E1a gene can
      efficaciously inhibit HER-2/neu-overexpressing ovarian cancer, and this promising
      procedure could greatly benefit ovarian cancer patients with high expression of
      HER-2/neu.

PMID- 11285028
TI  - Epidemiologic and mucosal immunologic aspects of HPV infection and HPV-related
      cervical neoplasia in the lower female genital tract: a review.
AB  - Human papillomavirus (HPV) infections are known to play an important role in the
      pathogenesis of cervical neoplasia. Considering the morbidity and mortality of
      cervical cancer, infection with HPV can be regarded as a worldwide problem,
      especially in developing countries. Currently, many studies focus on the
      development of both prophylactic and therapeutic HPV vaccines. Crucial for these
      vaccination protocols to be successful is that they will result in a long-lasting
      ability to generate an immune response that will eliminate the virus. HPV
      transmission and subsequent infection is a local event in the lower female
      genital tract and therefore the efficacy of vaccines against this locally
      transmitted infection can be best assessed by parameters of local immunity. In
      this review we describe both the epidemiology of HPV-related cervical neoplasia
      and the general aspects of mucosal immunity in the female genital tract while
      focusing on the local humoral immunity in HPV-related cervical neoplasia.

PMID- 11285030
TI  - Cervical cancer in Canada: changing patterns in incidence and mortality.
AB  - Data on incidence of cervical cancer by histologic subtype and mortality for the
      Canadian provinces of Ontario, Saskatchewan, and British Columbia were used to
      examine time trends by age, calender period, and birth cohort. Age-adjusted
      incidence rate of squamous cell carcinoma of the cervix decreased from 11.1 per
      100,000 women in 1970-72 to 5.3 in 1994-96, while the rate for cervical
      adenocarcinoma increased from 1.1 per 100,000 women to 1.5 over the same period.
      Age-adjusted mortality rate declined from 7.9 per 100,000 women in 1953-55 to 1.9
      in 1995-97. The patterns in age-specific mortality rates in 1953-72 were
      different from those in 1973-97; younger women experienced larger reductions in
      mortality during the earlier period while older women benefited to a greater
      extent during the latter period. Age-period-cohort modeling showed that cohort
      effects were responsible for the decreasing trends in incidence of squamous cell
      carcinoma of the cervix and increasing trends in adenocarcinoma, and both period
      and cohort effects account for the observed trends in mortality. The results
      suggest that Pap smear screening has played a significant role in the reduction
      in squamous cell cervical carcinoma. The causes for the increase in cervical
      adenocarcinoma are unclear.

PMID- 11285031
TI  - Limb sparing surgery for vulvar groin recurrence: a case report and review of the
      literature.
AB  - Hemipelvectomy was successfully avoided in a patient with extensive necrotic
      groin recurrence of vulvar cancer after prior radiation therapy. Tumor-free
      resection margins were achieved by wide excision of the recurrence including
      resection of the pubic bone and adjacent muscles. After resection of the femoral
      artery, blood supply to the leg was restored by an extra-anatomic axillopopliteal
      bypass. A myocutaneous flap from the contralateral rectus abdominis was used for
      primary wound closure. Limb salvage was achieved and the patient experienced pain
      relief, excellent cosmesis, and independent gait. Aspects of treatment options,
      even though primarily palliative, in groin recurrence of vulvar carcinoma are
      discussed.

PMID- 11285032
TI  - The presence of HPV DNA in cervical cancer: correlation with clinico-pathologic
      parameters and prognostic significance: 10 years experience at the Department of
      Obstetrics and Gynecology of the Mainz University.
AB  - The objective of this study was to assess whether the presence of human
      papillomavirus (HPV) DNA and/or several genotypes of HPV DNA in cervical cancer
      are correlated with several clinicopathologic parameters of well-defined
      prognostic significance and whether virologic parameters are predictors of long
      term survival in cancer patients. Two hundred twenty three cases of cervical
      cancer patients included in this retrospective study underwent follow-up
      evaluation. Survival and cause of death were examined for 204 (91.4%) patients,
      with a mean follow-up time of 4.4 years. HPV DNA was detected using the highly
      sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing
      for HPV genotyping. These results were correlated with well-defined
      clinicopathologic parameters and survival data. HPV DNA was detected by PCR in
      150 of 193 (73.4%) tissue specimens of cervical cancer patients. DNA sequence
      analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%)
      and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with
      histologic tumor types, node status, tumor oxygenation, blood vessel invasion,
      and lymph space involvement. The presence of HPV DNA in cervical cancer as well
      as the genotype of HPV 16 could also be confirmed as significant prognostic
      factors in the univariate Cox regression analysis (RR 2.856, P < 0.003 resp. RR
      3.444, P < 0.0001). In the multivariate analysis, however, HPV DNA status failed
      to be of prognostic relevance. Exclusively HPV 16 appears to have an independent
      impact on the overall survival in cervical patients (RR 3.653, P < 0.002). We
      conclude that the detection of HPV 16 genotype may play an important adjunct role
      in assessing prognosis of cervical cancer patients. The clinical impact of the
      presence of HPV DNA in primary tumors of uterine cervix remains to be
      investigated in further studies, and the exact mechanisms by which HPV influences
      the prognosis of cervical cancer patients have to be defined.

PMID- 11285033
TI  - Treatment results in women with clinical stage I and pathologic stage II
      endometrial carcinoma.
AB  - The aim of this study is to report survival and results of therapy and possible
      prognostic factors in women with pathologic stage II endometrial carcinoma. Forty
      two patients with pathologic stage II endometrial carcinoma were treated at the
      department of Radiation Oncology of the Medisch Spectrum Twente between 1987 and
      1998. All patients received external radiotherapy following standard surgical
      procedures and no adjuvant systemic therapy was given. From the 42 patients 21
      had a pathologic stage IIA and 21 stage IIB. The median follow-up was 62 months.
      The overall recurrence rate was 21.5% (9/42). Seven patients had distant
      metastasis, of which three also had locoregional recurrence, vaginal vault and/or
      pelvic. The presence of myometrial invasion (> (1/2)) and/or lymph-angioinvasion
      showed a significant relation with distant metastasis (P = 0.017). Stage IIB
      showed more recurrences, 33% (7/21). There was a significant different 5-year
      disease specific survival for stage IIA and IIB, respectively, 95% and 74% (P =
      0.0311). Patients with a differentiation grade 3 and stage IIB showed a
      significantly poorer (P = 0.003) 5-year survival of 48.6% (P = 0.003). Results
      obtained in the present series of patients are in accordance with the literature.
      The present treatment policy seems justified, except for patients with pathologic
      stage IIB and grade 3, in which a more aggressive treatment should be considered.

PMID- 11285034
TI  - Expression of interleukin-8 in human metastatic endometrial carcinoma cells and
      its regulation by inflammatory cytokines.
AB  - In the present study, we analyzed the expression of a multifunctional cytokine,
      interleukin-8 (IL-8), in metastatic endometrial carcinoma cells. Our data
      demonstrate that human serous papillary endometrial adenocarcinoma (SPEC) and
      human endometrial adenocarcinoma (HEC) cells expressed steady-state IL-8-specific
      mRNA transcript and secreted IL-8 protein. The levels of IL-8 mRNA in SPEC-2
      cells established from stage IV serous papillary adenocarcinoma were three-fold
      higher as compared to endometrial adenocarcinoma cells, HEC-1 A, established from
      stage IA endometrial cancer. Further, we observed higher levels of IL-8 mRNA and
      protein expression in the metastatic variants of SPEC-2 and HEC-1A cells as
      compared to the parent cell lines, demonstrating that IL-8 expression was
      associated with metastatic potential. Further, the treatment of endometrial
      carcinoma cells with inflammatory cytokines, IL-1beta and tumor necrosis factor
      alpha (TNF-alpha), demonstrated that IL-1beta and TNF-alpha induced IL-8
      expression in endometrial cancer cells. IL-1beta was a more potent inducer of IL
      8 expression than TNF-alpha in our studies. These data demonstrate that
      constitutive and induced IL-8 expression in endometrial carcinoma cells might be
      an important regulatory mechanism of tumor growth and metastasis.

PMID- 11285035
TI  - High dose rate intracavitary brachytherapy for recurrent or residual lesions in
      the vaginal cuff: results in post-hysterectomy patients with carcinoma of the
      cervix.
AB  - The purpose of this study was to assess the long-term survival, disease control,
      and complication rates of high dose rate intracavitary brachytherapy (HDR-ICR)
      alone or combined with external beam irradiation (HDR-ICR + EBRT) in patients
      with pathologically involved or close surgical margin in the vagina (Group 1) and
      recurrent lesions in the vaginal cuff (Group 2) following hysterectomy for
      cervical carcinoma. In Group 1, 10 patients received HDR-ICR only, and 11
      patients received HDR-ICR + EBRT with or without paravaginal shielding. In Group
      2, 8 patients received HDR-ICR only, and 11 patients received HDR-ICR + EBRT with
      or without paravaginal shielding. The HDR-ICR dose per fraction planned at the
      Apical Vaginal Point was 5-6 Gy per week. In Group 1, the 5-year absolute
      survival rates (AS), disease-free survival rates (DFS), and vaginal control rates
      (VC) were 81.0%, 76.2%, and 100%, respectively. The 5-year AS was lower in
      patients with parametrial infiltration or adenocarcinoma. In Group 2, the 5-year
      AS, DFS, and VC were 73.3%, 77.4% and 88.8%, respectively. The 5-year AS was
      lower when tumors were larger than 3 cm or infiltrated. Late complications
      occurred in 10 patients. In all but one patient, the complications were
      acceptable. All patients with cystitis, ileus, or leg edema received EBRT + HDR
      ICR. We recommend a treatment regimen of 25-30 Gy of HDR-ICR alone for Group 1
      patients without pathologically high risk of recurrence or Group 2 patients with
      superficial recurrent lesions, and a treatment regime of 50 Gy whole pelvis EBRT
      combined with 10-15 Gy HDR-ICR for Group 1 patients with pathologically high risk
      of recurrence or Group 2 patients with infiltrated recurrent lesions.

PMID- 11285036
TI  - Primary fallopian tube carcinoma: the Queensland experience.
AB  - The purpose of this study was to review the experience with fallopian tube
      carcinoma in Queensland and to compare it with previously published data. Thirty
      six patients with primary fallopian tube carcinoma treated at the Queensland
      Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective
      clinicopathologic study. All patients had primary surgery and 31/36 received
      chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal
      pain (14/36) were the most common presenting symptoms at the time of diagnosis.
      Median follow-up was 70.3 months and the median overall survival was 68.1 months.
      Surgical stage I disease (P = 0.02) and the absence of residual tumor after
      operation (P = 0.03) were the only factors associated with improved survival.
      Twenty of the 36 patients (55%) presented with stage I disease and survival was
      62.7% at 5 years. No patient with postoperative residual tumor survived. The
      majority of the patients with fallopian tube carcinoma present with stage I
      disease at diagnosis, but their survival probability is low compared with that of
      other early stage gynecological malignancies. If primary surgical debulking
      cannot achieve macroscopic tumor clearence, the chance of survival is extremely
      low.

PMID- 11285037
TI  - The new FIGO 2000 staging and risk factor scoring system for gestational
      trophoblastic disease: description and critical assessment.
AB  - The classification of the International Federation of Obstetrics and Gynecology
      (FIGO) for Trophoblastic Disease was changed at the meeting in Washington in
      September 2000 by combining the basic FIGO anatomic staging with the modified
      World Health Organization (WHO) risk factor scoring system. This presentation
      outlines the new system and provides a critical evaluation of the issues that
      have been resolved and those that are still outstanding.

PMID- 11285038
TI  - Extensive subcutaneous metastases from squamous cell carcinoma of the cervix in
      patient with HIV.
AB  - Advanced human immunodeficiency viral disease is associated with a high
      prevalence of cervical squamous intraepithelial and invasive lesions and probably
      with a rapidly progressive course of disease. Metastases to the skin occur rarely
      in cervical cancer, even in terminal stage of the disease. A patient with human
      immunodeficiency virus (HIV) for 14 years was diagnosed with squamous cell cancer
      of the cervix, Stage I-B2 in June 1997. She underwent successful radiotherapy.
      She then presented in January 1999 with recurrence evidenced by extensive
      subcutaneous nodules and multiple metastases. The patient developed rapidly
      progressive disease and died within two months. Patients with HIV and cervical
      cancer may present with a more aggressive course of disease. Aggressive treatment
      and closer follow-up may be indicated.

PMID- 11285039
TI  - Carcinosarcoma of ovary associated with previous radiotherapy.
AB  - Carcinosarcoma is a rare neoplasm which, in the female genital tract, arises
      mainly in the endometrium. Although the pathogenesis remains obscure, there is an
      apparent association between pelvic irradiation and uterine sarcomas. There have
      been sporadic case reports of the development of carcinosarcomas of the cervix,
      vagina, and extragenital areas, but not of the ovary, after previous pelvic
      irradiation. We describe a case of ovarian carcinosarcoma arising in a 74-year
      old female who had pelvic irradiation 33 years previously. Exploratory laparotomy
      showed a 25 x 18 x 9 cm left ovarian tumor with adjacent organ invasion including
      peri-uterine serosa and rectum. The patient was treated by optimal cytoreduction,
      followed by chemotherapy with adriamycin and cisplatin. However, acute hepatitis
      caused by reactivation of hepatitis B virus infection developed just before the
      fifth course of chemotherapy. She died of hepatic failure two weeks later.

PMID- 11285040
TI  - Hormone replacement therapy and cardiovascular risk: do abnormalities of
      coagulation and fibrinolysis matter?

PMID- 11285041
TI  - Should patients with hypertension receive antithrombotic therapy?
AB  - The main complications of hypertension, i.e. coronary heart disease, ischaemic
      strokes and peripheral vascular disease (PVD), are usually related to thrombosis.
      Increasing evidence also suggests that hypertension fulfils the components of
      Virchow's triad, thus conferring a prothrombotic or hypercoagulable state, as
      evident by abnormalities of haemostasis, platelets and endothelial function. It
      therefore seems plausible that use of antithrombotic therapy may help prevent
      these thrombosis-related complications of hypertension. Indeed, hypertensive
      patients with an estimated 10-year CHD risk > or = 15% will have their
      cardiovascular risk reduced by 25% using antihypertensive treatment, but the
      addition of aspirin further reduces major cardiovascular events by 15%. Recent
      guidelines recommend the use of aspirin 75 mg daily for hypertensive patients who
      have no contraindication to aspirin, in one of the following categories: (i)
      secondary prevention - cardiovascular complications (myocardial infarction,
      angina, non-haemorrhagic stroke, peripheral vascular disease or atherosclerotic
      renovascular disease); and (ii) primary prevention - those with blood pressure
      controlled to < 150/90 mmHg and one of: (a) age > or = 50 years and target organ
      damage (e.g. LVH, renal impairment, or proteinuria); (b) a 10-year CHD risk > or
      = 15%; or (c) type II diabetes mellitus. However, some of the risks of aspirin
      administration, namely increased incidence of major bleeding events, may possibly
      outweigh the benefits, especially in low-risk individuals.

PMID- 11285042
TI  - Cardiovascular disease in type 2 diabetes: challenge for treatment and
      prevention.
AB  - Type 2 diabetes increases the risk of cardiovascular disease (CVD) two- to
      fourfold compared with the risk in non-diabetic subjects. Although type 2
      diabetes is associated with a clustering of risk factors (small, dense low
      density lipoprotein [LDL] particles, low high-density lipoprotein [HDL]
      cholesterol, high triglycerides, elevated blood pressure, obesity, central
      obesity, hyperinsulinaemia, hyperglycaemia, etc.), the cause for an excess risk
      of CVD remains unknown. Recent drug treatment trials have indicated that the
      lowering of total and LDL cholesterol and blood pressure is similarly beneficial
      in diabetic and non-diabetic subjects. The treatment of hyperglycaemia reduces
      micro- and macrovascular complications in type 2 diabetic patients. Beta-blocking
      agents, angiotensin-converting enzyme inhibitors, aspirin, and thrombolytic
      therapy are also effective in the treatment of CVD amongst diabetic patients.

PMID- 11285043
TI  - Hormone replacement therapy in healthy postmenopausal women: a randomized,
      placebo-controlled study of effects on coagulation and fibrinolytic factors.
AB  - OBJECTIVES: To evaluate effects of postmenopausal hormone replacement therapy
      (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen,
      antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free
      protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen
      activator (tPA) and resistance to activated protein C. DESIGN: Part 1: double
      blind randomized trial for 3 months. Part 2: open study for 9 months. SETTING:
      Department of Endocrinology, University Hospital, Malmo, Sweden. SUBJECTS: Fifty
      one postmenopausal women with a history of amenorrhoea of at least 6 months and
      body mass index > or = 24 kg m-2 participated in part 1 and 46 participated in
      part 2. INTERVENTION: Randomization for placebo (n=24) or HRT (n=27). HRT was
      given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10
      mg medroxyprogesterone for 10 days every third month thereafter. MEASUREMENTS: At
      baseline and after 3 and 12 months. RESULTS: During 0-3 months in the HRT group,
      FVII increased (P < 0.01), whereas fibrinogen, AT III and total protein S all
      decreased (P < 0.001 for all). Changes in variables were expressed as Delta
      values. After 3 months Delta-values differed between groups for fibrinogen (P <
      0.05), AT III (P < 0.001), total protein S (P < 0.001), and PAI-1 (P < 0.001).
      During 0-12 months, fibrinogen, total protein S, tPA (P < 0.01 for all) and AT
      III (P < 0.05) decreased. In the control group, all variables were unchanged
      during the study, except for increases (P < 0.05) in total protein S after 3 and
      12 months, and a decrease (P < 0.01) in FVIII after 12 months. After 12 months
      Delta-values differed for fibrinogen (P < 0.05), AT III (P < 0.05) and total
      protein S (P < 0.001). CONCLUSIONS: Unopposed oestrogen substitution was
      associated with both potentially beneficial effects, such as decreases in
      fibrinogen, and potentially thrombogenic effects such as decreasing AT III and
      protein S and increasing FVII. During prolonged follow-up and addition of
      progesterone, differences between groups concerning FVII were attenuated. These
      data suggest that effects of HRT upon coagulation are most pronounced early after
      institution of unopposed treatment.

PMID- 11285044
TI  - Metaiodobenzylguanidine (MIBG) scintigraphy and computed tomography (CT) in
      clinical practice. Primary and secondary evaluation for localization of
      phaeochromocytomas.
AB  - OBJECTIVE: To determine the diagnostic value of metaiodobenzylguanidine (MIBG)
      scintigraphy compared with computed tomography (CT) for the localization of
      phaeochromocytomas in clinical practice. DESIGN: Retrospective comparison between
      MIBG scintigrams and CT for localization of phaeochromocytomas in all patients
      successively examined with MIBG scintigraphy in Malmo from 1984 until January
      1997. SETTING: Malmo University Hospital, Sweden. SUBJECTS: Sixty-four patients
      with clinically suspected phaeochromocytomas. MAIN OUTCOME MEASURES: MIBG
      scintigrams and CTs classified as positive or negative based on original
      interpretations (primary evaluation) and in a secondary evaluation by one blinded
      examiner are assessed through histological confirmation or clinical rule out of
      phaeochromocytomas. RESULTS: Twenty-five patients had surgically removed
      phaeochromocytomas. The remaining 39 patients had no proof of phaeochromocytomas.
      In the secondary evaluation, sensitivity for MIBG scintigraphy was 88% (22/25)
      and for CT was 100% (25/25). The specificity for MIBG scintigraphy was 89%
      (35/39) but only 50% for CT (18/36). Two out of a total of six extra-adrenal
      tumours were amongst the false-negative MIBG scintigrams. CONCLUSIONS: MIBG
      scintigraphy for the localization of phaeochromocytomas is superior to CT as far
      as specificity, whereas CT has a higher sensitivity. After biochemical diagnosis,
      CT will detect most phaeochromocytomas. MIBG scintigraphy can be of value in
      patients who show inconclusive results with biochemical testing and CT.

PMID- 11285045
TI  - Heart failure in the general population of men--morbidity, risk factors and
      prognosis.
AB  - AIMS: To analyse the prevalence, aetiology and prognosis of heart failure.
      METHODS AND RESULTS: A random population sample of men (n=7495) was examined at
      baseline in 1970-73 and followed until 1996. During up to 27 years, 937 men were
      hospitalized for heart failure. For the statistical analysis, odds ratios and 95%
      confidence intervals, multivariate logistic regression and time-dependent Cox
      analysis were used. The incidence rate was 2.1, 9.1 and 11.5 per 1000 person
      years in the age groups 55-64, 65-74 and 75-79, and the prevalences were 0.6, 2.8
      and 6.2%, respectively. Valvular heart disease was the aetiology in 5.8%,
      coronary heart disease only or in combination with hypertension in 58.8%, and
      hypertension only in 20.3%, and various combinations with diabetes in 4.5%. Of
      the remaining 12.1%, 96% were smokers and 64% were registered for alcohol abuse.
      Risk factors were increasing age, myocardial infarction in the family, diabetes
      mellitus, chest pain, tobacco smoking, high coffee consumption, alcohol abuse,
      high body mass index, high blood pressure as well as treatment for hypertension,
      but not high total cholesterol or psychological stress. Mortality after the
      diagnosis was increased eight times. CONCLUSIONS: Coronary heart disease and
      hypertension were the most common concomitant diseases. Risk factors were similar
      to those in coronary heart disease, and also alcohol abuse, but not high total
      cholesterol, low physical activity or psychological stress. Mortality was high.

PMID- 11285046
TI  - Increased mortality in diabetes during the first 10 years of the disease. A
      population-based study (DISS) in Swedish adults 15-34 years old at diagnosis.
AB  - OBJECTIVES: To study, prospectively, in young adult patients, the mortality
      during the first years after the diagnosis of diabetes. DESIGN: The Diabetes
      Incidence Study in Sweden (DISS) aims to register all incident cases aged 15-34
      years. During a 10-year period all deaths were identified by record linkage to
      the national Cause of Death Registry. SUBJECTS: During the period, 4097 new cases
      were registered and classified as type 1 diabetes (73%), type 2 (16%), secondary
      (2%) and unclassified (9%). The median follow-up was 5 years (21 001 person
      years). MAIN OUTCOME MEASURES: Calculation of the standardized mortality ratio
      (SMR) and 95% confidence interval (CI). Evaluation of all deceased by scrutiny of
      clinical records, death certificates and autopsy protocols. RESULTS: Fifty-eight
      patients died, corresponding to an SMR of 3.5 (CI=2.7-4.5), which increased from
      1.5 at 15-19 years to 4.1 at 30-34 years. SMR was 2.7 in primary diabetes: 2.3
      (1.6-3.3) in type 1 and 4.1 (2.6-6.7) in type 2. In secondary diabetes, alcohol
      associated pancreatitis a common cause, SMR was 32 (CI=24-45). Evidence of
      alcohol or drug misuse, mental dysfunction or suicide was found in 40 of all 58
      deceased cases. Less often, hypoglycaemia (n=7) or hyperglycaemia-ketoacidosis
      (n=11) was present at death. Unexplained 'dead in bed' was found once.
      CONCLUSIONS: In the investigated population-based cohort the early mortality was
      about threefold increased. Hypoglycaemia and ketoacidosis per se played a
      relatively small role compared with a heavy impact from social and mental
      dysfunction, and from careless use of alcohol or drugs.

PMID- 11285047
TI  - Appropriate treatment of hypernatraemia in diabetic hyperglycaemic hyperosmolar
      syndrome.

PMID- 11285049
TI  - Daytime variations in central nervous system activation measured by a
      pupillographic sleepiness test.
AB  - Pupil size is regulated exclusively by the autonomic nervous system, and in
      darkness is proportional to the level of central sympathetic tone. Spontaneous
      pupillary movements, while at rest in darkness and quiet, were recorded for a
      period of 11 min, using infrared video pupillography. Thirteen young adults took
      part in a 30-h experiment lasting from 08.00 h to 14.00 h on the following day.
      Pupillographic testing and completion of a self-rated scale for the estimate of
      sleepiness were repeated every two hours. Pupillary unrest index (PUI), as a
      measure of pupil size instability associated with daytime sleepiness, showed the
      lowest values at 09.00 h, when pupil size was found to be maximal, and 23.00 h.
      During the course of the day, amplitude spectrum < or = 0.8 Hz and PUI showed
      increasing values during the afternoon hours, followed by a decrease during the
      evening. Daytime variations in the pupillary unrest index in healthy normal
      subjects were found to be positively correlated with the level of alertness.
      These findings are similar to the daytime variations found by the MSLT (multiple
      sleep latency test) in young adults.

PMID- 11285050
TI  - P300 and sleep-related positive waveforms (P220, P450, and P900) have different
      determinants.
AB  - Stimulus factors known to influence the amplitude of the well known endogenous
      event-related potential (ERP) component P300 were manipulated to determine
      whether they have the same, or a different, influence on the amplitude of
      positivities of the sleep ERPs identified as P220, P450, and P900. Behavioral
      responsiveness and ERPs were recorded as subjects moved from wakefulness to sleep
      while performing an oddball task. The task consisted of sequential presentation
      of target and non-target tone stimuli with instructions to respond to targets
      with a finger--lift response. The probability of the target and non-target
      stimuli was varied (0.2/0.8, 0.5/.05 and 0.8/0.2) across three test conditions.
      While subjects were awake, P300 was maximal parietally with amplitude inversely
      related to the relative probability of the evoking stimulus and directly related
      to its task relevance. Positive waveforms (P220, P450, P900) recorded in sleep
      were largest at frontal and central recording sites. P220 and P900 amplitudes
      were inversely related to stimulus probability. P220 was smaller following target
      relative to non-target stimuli. Processes underlying P220, P450, and P900 sleep
      related waveforms are different from those underlying the P300 component seen in
      alert wakefulness. The sleep positivities may be state-related waveforms subject
      to modulation by psychological processes.

PMID- 11285051
TI  - Urinary free cortisol and sleep under baseline and stressed conditions in healthy
      senior women: effects of estrogen replacement therapy.
AB  - The purpose of this study was to examine the effects of a mild 24-h stress
      (indwelling IV catheter) on cortisol and sleep in postmenopausal women, and to
      evaluate differences due to estrogen replacement therapy (ERT) status. This
      study, conducted in the General Clinical Research Center at the University of
      Washington Medical Center, examined sleep, cortisol and sleep-cortisol
      relationships in both baseline and stress conditions, and compared women on ERT
      with women not on ERT. Forty-two women (age=69.6 +/- 6.2 years [SD]), of whom 20
      were on ERT, participated. Urinary free cortisol (UFC) levels and sleep
      polysomnography were measured over both 24-baseline and stress condition. Sleep
      was impaired in the stress condition for both groups; mean UFC levels were
      higher, sleep efficiency and minutes of stages 2, 3 and 4 sleep were reduced, and
      morning risetime was earlier in the stress than baseline condition. For the
      combined groups, age-controlled correlations between 24-h UFC and sleep were
      significant in both conditions: at baseline, UFC levels were associated with
      earlier time of rising and less REM sleep, and under stress with reduced sleep
      efficiency, there was reduced minutes of stages 2, 3, 4 sleep, reduced REM sleep,
      and an earlier risetime. The pattern of negative significant correlations between
      UFC and sleep/sleep timing remained when plasma estrogen was statistically
      controlled; however, when groups were examined separately, the significant
      negative UFC-sleep relationships were confined to the non ERT group. Elevated 24
      h UFC is associated with impaired sleep and earlier awakening in older women not
      on ERT, but not in women on ERT.

PMID- 11285052
TI  - Sleep deprivation blunts the night time increase in aldosterone release in
      humans.
AB  - The aim of this study was to determine the effect of sleep deprivation on the 24
      h profile of aldosterone and its consequences on renal function. Aldosterone and
      its main hormonal regulatory factors, ACTH (evaluated by cortisol measurement)
      and the renin-angiotensin system [RAS, evaluated by plasma renin activity (PRA)
      measurement] were determined every 10 min for 24 h in eight healthy subjects in
      the supine position, once with nocturnal sleep and once during total 24-h sleep
      deprivation. Plasma Na(+) and K(+) were measured every 10 min in four of these
      subjects. In an additional group of 13 subjects under enteral nutrition,
      diuresis, natriuresis and kaliuresis were measured once during the sleep period
      (23.00--07.00 h) and once during a 23.00--07.00 hours sleep deprivation period.
      During sleep deprivation, aldosterone displayed lower plasma levels and pulse
      amplitude in the 23.00--07.00-hour period than during sleep. Similarly, PRA
      showed reduced levels and lower pulse frequency and amplitude. Plasma cortisol
      levels were slightly enhanced during sleep deprivation. Overnight profiles of
      plasma K(+) and Na(+) were not affected. Diuresis and kaliuresis were not
      influenced by sleep deprivation. In contrast, natriuresis significantly increased
      during sleep deprivation. This study demonstrates that sleep deprivation modifies
      the 24-h aldosterone profile by preventing the nocturnal increase in aldosterone
      release and leads to altered overnight hydromineral balance.

PMID- 11285053
TI  - The effects of total sleep deprivation, selective sleep interruption and sleep
      recovery on pain tolerance thresholds in healthy subjects.
AB  - The aim of this study was to compare the effects of total sleep deprivation
      (TSD), rapid eye movement (REM) sleep and slow wave sleep (SWS) interruption and
      sleep recovery on mechanical and thermal pain sensitivity in healthy adults. Nine
      healthy male volunteers (age 26--43 years) were randomly assigned in this double
      blind and crossover study to undergo either REM sleep or SWS interruption.
      Periods of 6 consecutive laboratory nights separated by at least 2 weeks were
      designed as follows: N1 Adaptation night; N2 Baseline night; N3 Total sleep
      deprivation (40 h); N4 and N5 SWS or REM sleep interruption; N6 Recovery. Sleep
      was recorded and scored using standard methods. Tolerance thresholds to
      mechanical and thermal pain were assessed using an electronic pressure
      dolorimeter and a thermode operating on a Peltier principle. Relative to baseline
      levels, TSD decreased significantly mechanical pain thresholds (-8%). Both REM
      sleep and SWS interruption tended to decrease mechanical pain thresholds.
      Recovery sleep, after SWS interruption produced a significant increase in
      mechanical pain thresholds (+ 15%). Recovery sleep after REM sleep interruption
      did not significantly increase mechanical pain thresholds. No significant
      differences in thermal pain thresholds were detected between and within periods.
      In conclusion this experimental study in healthy adult volunteers has
      demonstrated an hyperalgesic effect related to 40 h TSD and an analgesic effect
      related to SWS recovery. The analgesic effect of SWS recovery is apparently
      greater than the analgesia induced by level I (World Health Organization)
      analgesic compounds in mechanical pain experiments in healthy volunteers.

PMID- 11285054
TI  - Intrinsic dreams are not produced without REM sleep mechanisms: evidence through
      elicitation of sleep onset REM periods.
AB  - The hypothesis that there is a strict relationship between dreams and a specific
      rapid eye movement (REM) sleep mechanism is controversial. Many researchers have
      recently denied this relationship, yet none of their studies have simultaneously
      controlled both sleep length and depth prior to non-REM (NREM) and REM sleep
      awakenings, due to the natural rigid order of the NREM--REM sleep cycle. The
      failure to control sleep length and depth prior to arousal has confounded
      interpretations of the REM-dreams relationship. We have hypothesised that
      different physiological mechanisms underlie dreaming during REM and NREM sleep,
      based on recent findings concerning the specificity of REM sleep for cognitive
      function. Using the Sleep Interruption Technique, we elicited sleep onset REM
      periods (SOREMP) from 13 normal subjects to collect SOREMP and sleep onset NREM
      (NREMP) dreams without the confounds described above. Regression analyses showed
      that SOREMP dream occurrences were significantly related to the amount of REM
      sleep, while NREMP dream occurrences were related to arousals from NREM sleep.
      Dream properties evaluated using the Dream Property Scale showed qualitative
      differences between SOREMP and NREMP dream reports. These results support our
      hypothesis and we have concluded that although 'dreaming' may occur during both
      REM and NREM periods as previous researchers have suggested, the dreams obtained
      from these distinct periods differ significantly in their quantitative and
      qualitative aspects and are likely to be produced by different mechanisms.

PMID- 11285055
TI  - A genetic analysis of the Epworth Sleepiness Scale in 1560 World War II male
      veteran twins in the NAS-NRC Twin Registry.
AB  - Responses to the eight-item Epworth Sleepiness Scale (ESS) obtained from 1560
      World War II male veteran twin pairs [818 monozygotic (MZ), 742 dizygotic (DZ)]
      were analysed to determine the extent to which genetic influences are involved in
      self-reported daytime sleepiness in the elderly. Average ESS score (+/- SD) in
      this sample was 7.1 +/- 3.9, range 0--24. More than half of the twins (65%--67%)
      reported a moderate to high chance of falling asleep while lying down to rest;
      fewer than 3% admitted that this would occur while sitting and talking to someone
      or while stopped in traffic. Daytime sleepiness was not associated with age but
      was significantly and positively associated with obesity. The intraclass twin
      correlation on ESS scores was 0.39 in MZ pairs and 0.21 in DZ pairs (both P <
      0.001). Structural equation modeling of the observed variance-covariance matrices
      for MZ and DZ twins estimated the heritability of ESS to be 38% (95% confidence
      interval 33%--44%). Environmental influences not shared by twin brothers
      accounted for the remaining variance in daytime sleepiness. A reasonable
      interpretation of the heritability of ESS in this healthy cohort of elderly male
      twins is a genetic susceptibility for disordered breathing during sleep.

PMID- 11285056
TI  - Development of sleep patterns in early adolescence.
AB  - This study examines the developmental changes of sleep patterns as a function of
      gender and puberty and assesses the prevalence of sleep habits and sleep
      disturbances in early adolescence. It also investigates the relationship between
      sleep patterns, sleep habits and difficulty falling asleep and nocturnal
      awakenings. The present analyses are based on results available for 588 boys and
      558 girls for whom mothers completed questions concerning demographics and sleep
      at annual intervals when their child was aged 10--13 years. The results indicated
      that nocturnal sleep times decreased, bedtimes were delayed and differences
      between weekend and school day sleep schedules progressively increased with age.
      Gender and puberty were both associated with the timing of sleep on weekends.
      Girls presented longer weekend time in bed (TIB) and later weekend wake time than
      boys. Similarly, subjects with higher pubertal status showed longer weekend TIB
      and later weekend wake time than subjects with lower pubertal status. Difficulty
      falling asleep was associated with later weekend wake time and with sleeping with
      a night light. In conclusion, the gender differences commonly reported in
      adolescents' sleep patterns are most likely explained by girls' higher pubertal
      status. This study emphasizes the link between puberty and a putative
      physiological need for more sleep, in presence of a general reduction of sleep
      times during adolescence. From age 10--13 years, the delay and lengthening of the
      sleep period on weekends in comparison to schooldays is associated with
      difficulty falling asleep.

PMID- 11285057
TI  - Sleep complaints and risk factors for excessive daytime sleepiness in adult males
      in Northern Ireland.
AB  - The prevalence of sleep complaints in Northern Ireland is unknown. Sleep
      disruption can result in excessive daytime sleepiness (EDS), with significant
      socioeconomic consequences. The aim of this study was to assess the prevalence of
      sleep complaints and to determine risk factors for EDS in a Northern Irish
      community. From an urban and rural community of 499,111 people, a random sample
      of 3391 adult men were sent a questionnaire by mail. Questions were asked
      regarding sleep, EDS and medical history. There were 2364 completed
      questionnaires returned (response rate 70%). The mean age of respondents was 46.0
      years (range 18--91 years). 26.7% of men were not satisfied with their usual
      night's sleep and 68% of men woke up at least once during the night. Based on pre
      defined criteria, 24.6% of the population had insomnia and 19.8% had EDS. The
      strongest risk factor identified for EDS was a history of snoring loudly (odds
      ratio 2.62; 95% CI 1.82--3.77). Other risk factors included ankle swelling,
      feeling sad or depressed stopping sleep, experiencing vivid dreams while falling
      asleep, waking up feeling unrefreshed and age > 35 years. The prevalence rates of
      sleep complaints and EDS in this community-based study is high, although this
      does depend directly on the criteria used to define insomnia and EDS. Recognition
      of risk factors for EDS may help to identify and treat those affected.

PMID- 11285058
TI  - Health-related quality of life in narcolepsy.
AB  - Narcolepsy is a chronic sleep disorder characterised by symptoms of excessive
      daytime sleepiness and cataplexy. The aim of this study was to describe the
      health-related quality of life of people with narcolepsy residing in the UK. The
      study comprised a postal survey of 500 members of the UK narcolepsy patient
      association, which included amongst other questions the UK Short Form 36 (SF-36),
      the Beck Depression Inventory (BDI), and the Ullanlinna Narcolepsy Scale (UNS). A
      total of 305 questionnaires were included in the final analysis. The results
      showed that the subjects had significantly lower median scores on all eight
      domains of the SF-36 than normative data, and scored particularly poorly for the
      domains of role physical, energy/vitality, and social functioning. The BDI
      indicated that 56.9% of subjects had some degree of depression. In addition, many
      individuals described limitations on their education, home, work and social life
      caused by their symptoms. There was little difference between the groups
      receiving different types of medication. This study is the largest of its type in
      the UK, although the limitations of using a sample from a patient association
      have been recognised. The results are consistent with studies of narcolepsy in
      other countries in demonstrating the extensive impact of this disorder on health
      related quality of life.

PMID- 11285059
TI  - Serum levels of neutrophil activation cytokines in Kawasaki disease.
AB  - BACKGROUND: The aim of the present study was to investigate whether neutrophils
      are early effector cells for vascular endothelial damage in the acute phase of
      Kawasaki disease (KD) by examining serial changes in neutrophil counts and serum
      levels of neutrophil activation cytokines, such as granulocyte colony stimulating
      factor (G-CSF) and interleukin (IL)-8. METHODS: From October 1994 to June 1998, a
      total of 52 patients with KD were included in the study. Thirty-three patients
      had some infectious diseases, while 20 healthy children served as control
      subjects. Serial changes in neutrophils were counted by the optimal Wright-Giemsa
      staining method and serum levels of IL-8 and G-CSF in patients with KD were
      measured by an enzyme-linked immunosorbent assay system. RESULTS: Serum G-CSF
      levels both before and after intravenous immunoglobulin therapy (IVIG; P<0.05)
      and neutrophil counts after IVIG (P<0.005) were higher in KD patients with
      coronary arterial lesions (CAL) than those without CAL. However, serum IL-8
      levels before and after IVIG showed no significant differences in these two
      groups. CONCLUSIONS: These data suggest that neutrophils may be important as
      early effector cells for vascular endothelial damage and that G-CSF may play a
      more important role than IL-8 in KD.

PMID- 11285060
TI  - Retinopathy of prematurity: mutations in the Norrie disease gene and the risk of
      progression to advanced stages.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a retinal vascular disease that
      occurs in infants with short gestational age and low birth weight and may lead to
      retinal detachment and blindness. Missense mutations in the Norrie disease (ND)
      gene have been associated with the risk of progression to advanced stages in
      cases of ROP from the US and also in clinically similar ND and familial exudative
      vitreoretinopathy. METHODS: We have screened two ND gene mutations, namely A105T
      and Val60Glu, by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and allele-specific PCR methods, respectively, in 210
      Kuwaiti premature newborns to replicate these findings in a different ethnic
      group. RESULTS: In the Kuwaiti premature newborn cohort, 115 of 210 babies had no
      eye problems and served as controls, while 95 were cases of ROP. In 71 of 95 ROP
      cases, the disease regressed spontaneously on or before stage 3, while in 24 of
      95 ROP cases the disease progressed to advanced stages 4 and 5. In case of
      missense mutation (A105T), the AA genotype was detected in 96% of controls
      compared with 87% of ROP cases (NS); similarly no significant difference was
      found between spontaneously regressed ROP cases and those who progressed to
      advanced stages. For the Val60Glu mutation, no significant association was
      detected between the genotype and progression of ROP to advanced stages.
      CONCLUSIONS: Unlike data from the US, our findings from a Kuwaiti cohort of ROP
      cases and controls suggest a lack of association between the two ND gene
      mutations (A105T and Val60Glu) and ROP and the risk of progression of the disease
      to advanced stages.

PMID- 11285061
TI  - Low-dose doxapram therapy for idiopathic apnea of prematurity.
AB  - BACKGROUND: Doxapram is contraindicated for newborn infants in Japan because of
      its serious side effects. However, because of encouraging results of recent
      studies regarding the efficacy and safety of therapy for apnea of prematurity
      (AOP) with lower doses of doxapram than those previously proposed, approximately
      60% of Japanese neonatologists continue to use doxapram at small doses. Caution
      is warranted because the sample sizes of the former studies are inadequate to
      evaluate doxapram for both its beneficial and harmful effects. Therefore, we
      conducted the present study in order to investigate the efficacy and harmful
      events of low-dose doxapram therapy for idiopathic AOP in very low-birth weight
      (VLBW) infants in a larger population. METHODS: One hundred and six VLBW infants
      with idiopathic AOP were treated with doxapram at a dose of 0.2-1.0 mg/kg per h
      in combination with methylxanthines and the frequency of apnea and secondary
      outcomes were compared with a group of control infants. RESULTS: An approximate
      80% reduction in the frequency of apnea was found with only minimal side effects
      following low-dose doxapram. Although there were no significant differences in
      secondary outcomes between the doxapram-treated and control groups, mortality in
      doxapram-treated infants was significantly lower than that in control infants.
      CONCLUSIONS: Patients with AOP unresponsive to treatment with methylxanthines may
      benefit from the addition of low-dose doxapram.

PMID- 11285062
TI  - Growth and endocrine function during school age in very low-birth weight infants.
AB  - BACKGROUND: Short stature and low bodyweight are commonly encountered problems in
      the clinical follow up of premature infants. However, details about the
      underlying pathophysiology are unknown in these cases. METHODS: Evaluations of
      growth and endocrine function were performed in 23 very low-birth weight (VLBW)
      infants between 11.3 and 14.3 years of age. RESULTS: The mean (+/-SD) scores for
      height and weight were -0.50+/-0.97 and -0.50+/-1.10 SD, respectively. Mean serum
      insulin-like growth factor (IGF)-I and urine growth hormone (GH) levels were
      402+/-138 ng/mL and 18.0+/-17.5 pg/mg creatinine, respectively. Serum IGF-I and
      urine GH levels were within the normal range for all patients. The bone age
      values were consistent with the patient's true age. Physical signs of puberty
      were detected in 15 of 23 patients (65%). Using bone ages to predict final adult
      height yielded a score of -0.52+/-1.08 SD. CONCLUSIONS: Despite the almost normal
      results of serum IGF-I, urine GH levels and bone age, the physical growth of
      these VLBW infants was less than that of normal birth weight children, as was
      their predicted adult growth.

PMID- 11285063
TI  - Systemic effects of transdermal testosterone for the treatment of microphallus in
      children.
AB  - OBJECTIVES: To elucidate the metabolic effects of topical testosterone for the
      treatment of microphallus in children. METHODS: We administered 5% testosterone
      ointment to 50 prepubertal boys for the treatment of microphallus, allowing us to
      observe its metabolic effect on plasma concentrations of testosterone as a marker
      of transdermally absorbed testosterone, insulin-like growth factor (IGF)-I as a
      marker of growth hormone secretion status, and osteocalcin as a marker of bone
      metabolic turnover. RESULTS: Transdermal application of testosterone for 30 days
      at a dose that affects penile growth increased mean (+/-SD) plasma testosterone
      concentrations from 7.5+/-5.1 to 31.0+/-8.2 ng/dL (pre- vs. post-treatment,
      respectively; P<0.01). This was associated with a slight but statistically
      significant elevation of IGF-I concentrations (117.2+/-76.9 vs. 154.4+/-81.5
      ng/mL; P<0.05). No significant change in osteocalcin levels was found.
      CONCLUSIONS: When using testosterone ointment as a treatment for microphallus, it
      should be borne in mind that this application has systemic effects.

PMID- 11285064
TI  - Evaluation of growth hormone secretion after completion of therapy.
AB  - BACKGROUND: Growth hormone (GH) reserve in young adults previously diagnosed as
      having GH insufficiency, who were treated with human (h)GH replacement in
      childhood needs confirmation in adulthood. METHODS: Nine patients (seven males,
      two females; two empty cella, one hypoplasia of the hypophysis and six with
      idiopathic GH deficiency) diagnosed as having GH insufficiency by the insulin
      tolerance test (ITT) and dopamine stimulation test in childhood (mean age 12.8+/
      2.6 years) were retested at completion of linear growth (mean age 21.0+/-3.0
      years), 4.6+/-1.6 years after discontinuation of hGH therapy. RESULTS: At the
      initial diagnosis, seven had complete and two had partial GH deficiency. At
      diagnosis, the mean peak GH response to ITT and dopamine was 4.8+/-4.08 and 3.4+/
      2.9 mU/L, respectively. At retesting, the mean GH response to ITT and dopamine
      stimulation was 3.5+/-2.5 and 3.3+/-3.1 mU/L, respectively (P=0.91 and 0.96,
      respectively). During hGH therapy, mean height velocity increased from 3.5+/-1.9
      cm/year at diagnosis to 9.9+/-3.64 cm/year during the first year (P=0.002). One
      of nine children diagnosed as having GH insufficiency who was treated with hGH
      replacement had normal growth hormone secretion at completion of linear growth.
      CONCLUSIONS: All GH-insufficient children should be retested after completion of
      their hGH treatment and linear growth to identify those who are truly GH
      insufficient and who may benefit from GH therapy in adulthood.

PMID- 11285065
TI  - High prevalence of eosinophilia in growth hormone-deficient children.
AB  - BACKGROUND: To determine the clinical significance of eosinophilia in growth
      hormone (GH)-deficient children, a clinical study consisting of 72 children and
      adolescents (mean age 9 years and 6 months at diagnosis) with GH deficiency (GHD)
      was undertaken. Patients were treated with GH, along with supplementation for the
      combined deficiency in patients with multiple hormone deficiency. METHODS: A
      complete blood count and hemogram with microscopic examination of a peripheral
      blood smear was performed. RESULTS: Before treatment, differential eosinophil
      counts exceeded 5% in 30 subjects (41.7%) and absolute eosinophil counts were
      >350 /microL in 27 subjects (37.5%). Growth hormone therapy did not significantly
      affect eosinophil counts. There was an inverse relationship between absolute
      eosinophil count and peak GH value in response to the L-dopa stimulation test
      (n=65; Rs=-0.252; P=0.044). CONCLUSIONS: For the diagnosis of GHD, one should
      take into account that GH response to L-dopa stimulation can be selectively
      blunted in patients with eosinophilia.

PMID- 11285067
TI  - Frequency of portal and systemic bacteremia in acute appendicitis.
AB  - BACKGROUND: Acute appendicitis is the most common condition requiring an
      emergency abdominal operation in childhood. In the present study, we analyzed the
      frequency of portal and systemic bacteremia in 42 patients with acute
      appendicitis and determined the microbial agents responsible for an acute
      appendicitis and for portal and systemic bacteremia. METHODS: Appendectomies were
      performed on 50 young patients (5-18 years of age), as well as clinical and
      bacteriological tests. Six independent samples from each patient isolated from
      the peripheral vein, superior mesenteric vein, appendix and peritoneum were
      obtained prior to surgery, during surgery and after surgery for biochemical,
      immunologic and bacteriologic examination. RESULTS: Pathohistology confirmed the
      diagnosis of appendicitis in 42 patients, while in the other eight patients there
      were no obvious pathologic findings, so they served as a control group. Of 50
      patients with a clinical appearance of acute appendicitis, in 19 patients (38%)
      we detected portal bacteremia in the mesenteric vein, while in only three cases
      (6%) did we find systemic bacteremia detected from the peripheral vein.
      Furthermore, bacteriologic analysis revealed that Bacteroides spp. and
      Escherichia coli were the predominant species isolated. CONCLUSIONS: The results
      presented in this paper suggests that portal bacteremia did not influence
      peripheral blood reactions. Furthermore, in the present study we have found a
      positive correlation between the smear and bacteremia of the superior mesenteric
      vein, but not with the bacteremia of systemic blood.

PMID- 11285066
TI  - Diastolic flow velocity of the left pulmonary artery of patent ductus arteriosus
      in preterm infants.
AB  - BACKGROUND: The usefulness of diastolic pulmonary flow velocity determined by
      echocardiography in the assessment of symptomatic patent ductus arteriosus (sPDA)
      in preterm infants has not been confirmed. METHODS: Echocardiography was
      performed daily in infants ranging from 23 to 31 gestational weeks of age, and
      diastolic flow velocity of the left pulmonary artery (DFLPA) was measured. The
      DFLPA data before indomethacin administration for sPDA were compared with data
      obtained after indomethacin administration. The normal range of DFLPA was also
      determined from serial measurements performed in infants who did not develop sPDA
      during the first 7 days of life. Then, this range was compared with data from
      infants who did develop sPDA during this time. RESULTS: In infants who underwent
      indomethacin treatment, DFLPA increased with the development of sPDA and
      decreased when the symptoms of sPDA disappeared. On the basis of results from
      serial DFLPA measurement, the sensitivity and specificity of DFLPA for assessing
      sPDA was found to be 0.82 and 0.83, respectively. CONCLUSIONS: Measurement of
      DFLPA by echocardiography is a useful method for assessing sPDA in preterm
      infants.

PMID- 11285068
TI  - Bone mineral density in children with cerebral palsy.
AB  - BACKGROUND: The purpose of the present study was to evaluate the severity of and
      factors related to osteopenia in children with cerebral palsy (CP). METHODS: Bone
      mineral density (BMD), calcium (Ca), phosphate (P), alkaline phosphatase (ALP),
      creatinine, parathyroid hormone (PTH) and 25-hydroxy vitamin D3 (25OHD3)
      concentrations were determined in 24 children with CP (15 ambulant, nine non
      ambulant), aged between 10 months and 12 years (mean (+/-SD) 4.1+/-2.9 years).
      These vaules were compared with data obtained from a control group. RESULTS:
      Adjusted mean BMD values were lower in the patient group than in controls
      (P<0.05). However, there was no difference between BMD values of ambulant and non
      ambulant patients. The Ca and P levels of the patient group were significantly
      higher than those of controls (P<0.05). CONCLUSIONS: The present study showed
      that BMD was decreased in all children with CP, but to a greater extent in non
      ambulant children with CP, and immobilization is the major effective factor on
      bone mineralization.

PMID- 11285069
TI  - Disseminated tuberculosis in acute leukemia.

PMID- 11285070
TI  - Salmonella infection of an ovarian dermoid cyst.

PMID- 11285071
TI  - Acute disseminated encephalomyelitis in a boy with elevated plasma levels of
      thrombin-antithrombin III complex.

PMID- 11285072
TI  - Successful donor lymphocyte infusion in a patient with relapse of lymphoblastic
      leukemia after bone marrow transplantation.

PMID- 11285073
TI  - Prune-belly syndrome and pulmonary hypoplasia: a potential cause of death.

PMID- 11285074
TI  - Transcatheter closure of patent ductus arteriosus in an infant weighing 1180 g.

PMID- 11285075
TI  - Secondary arteriovenous fistula after a single arterial puncture.

PMID- 11285076
TI  - A case of Schinzel-Giedion syndrome complicated with progressive severe gingival
      hyperplasia and progressive brain atrophy.

PMID- 11285077
TI  - Changes in leptin and testosterone levels in a girl with congenital adrenal
      hyperplasia during hydrocortisone therapy.

PMID- 11285079
TI  - Postnatal depression in Japanese mothers and the reconsideration of 'Satogaeri
      bunben'.
AB  - BACKGROUND: Postnatal depression occurs in 10-15% of Western women. In Japan,
      there is a traditional support system for perinatal women and there have been few
      prospective studies on postnatal depression in terms of cross-cultural studies.
      METHODS: First, a cross-cultural study on postnatal depression was performed.
      Ninety-eight Japanese women living in England and 88 Japanese women living in
      Japan were recruited and followed up to 3 months postnatally. The Edinburgh
      Postnatal Depression Scale (EPDS) and Schedule for Affective Disorder and
      Schizophrenia were used as a self-report questionnaire and psychiatric diagnostic
      interview. Diagnoses of depression were made by Research Diagnostic Criteria.
      Second, a study on 'Satogaeri bunben' (a traditional ritual (support system) for
      perinatal women in Japan; 'Satogaeri' means returning to the original family town
      or house and 'bunben' means delivery) was undertaken. Seventy-five mothers were
      asked to answer the questionnaire 6 months postnatally. The questionnaire was
      devised by the authors about the choice of Satogaeri bunben and the reasons for
      the decision. RESULTS: The incidence of postnatal depression was 12 and 17% in
      the English and Japanese groups of mothers, respectively. However, subjects from
      both groups supressed expression of their depressed mood in answering the EPDS.
      Satogaeri bunben itself did not lower the incidence of postnatal depression. In
      the study on Satogaeri bunben, 23 of 75 women did not choose Satogaeri bunben;
      moreover, seven of these women did not have good support from their own mothers.
      DISCUSSION: Having found that postnatal depression is not uncommon in Japanese
      women, a screening system should be developed, in particular because Japanese
      women would not naturally express their emotions, and Satogaeri bunben needs to
      be reconsidered qualitatively.

PMID- 11285080
TI  - Evolution of the perinatal care system.
AB  - BACKGROUND: The perinatal support system for mothers and babies, which has
      evolved over the past 6 years at the Morioka Red Cross Hospital, is described.
      METHODS: Between July 1995 and August 1999, 1864 puerperal mothers at the Morioka
      Red Cross Hospital responded to the Maternity Blues Scale (MB) and the Edinburgh
      Postnatal Depression Scale (EPDS) at 1 month, each with an open comment form.
      RESULTS AND DISCUSSION: There was a significant difference in each MB item
      between individuals who scored above 9 points and those who scored lower in the
      EPDS. Those who later scored high in the EPDS had responses to a preceding MB
      where we had checked items of 'confusion', 'experience of crying', 'anxiety',
      'exhaustion', 'feeling depressed', 'nervousness', 'agitation' and
      'forgetfulness'. Administration of the MB and provision of a free comment form
      significantly decreased EPDS scores. Ensuring that the views of mothers are
      acknowledged within the context of an adequate care system is central to
      effective perinatal care.

PMID- 11285081
TI  - Infant abuse in Osaka: Health center activities from 1988 to 1999.
AB  - BACKGROUND: In 1988, the first survey of child abuse in Japan was conducted in
      Osaka Prefecture as a joint effort between medical, health and welfare agencies.
      Ensuing surveys in 1988 revealed that infant abuse had a death rate of 10% in
      Health Center. METHODS: In 1996 and 1999, surveys were performed on 130 and 215
      abused children under 18 years of age. They were studied in terms of their
      activity of Health Center, including help, means of involvement by health
      visitors. RESULTS: Fifty-five percent of children were detected via health
      centers. In 69% of cases, health visitors listened to parents and promptly
      contacted other agencies. Ninety-five percent of cases had home visits. The
      concerted effort of the health centers with allied disciplines in Osaka
      Prefecture yielded the following changes: the mortality rate decreased from 9.8%
      in 1988 to 2.3% in 1996, and institutionalized cases tripled from 13.7% in 1988
      to 39.5% in 1999. The rate of admission to day care centers increased from 22.4%
      in 1988 to 58.7% in 1999. Along with the constant support of health visitors, day
      care centers provided secure support and protection for parents and infants.
      CONCLUSIONS: Effective prevention and treatment become possible only when
      treatment of the child's physical and psychological health, mental care for
      parents and tangible support for childrearing and daily life were undertaken in a
      concerted way. To this end, a systematic commitment of all child agencies, child
      guidance centers, as well as medical, health educational, welfare and other
      allied disciplines is required.

PMID- 11285082
TI  - Early intervention for infants with autistic spectrum disorders in Japan.
AB  - BACKGROUND: To date, many researchers in Japan have assumed that the cause of
      autistic spectrum disorders is attributable to some disorder in the ability of
      the child. However, we have been working on the premise that autistic spectrum
      disorders are brought about by relationship disturbances in early infancy and
      have been attempting to validate this hypothesis through early intervention.
      METHODS: We have examined the developmental process of affective communication in
      infants with autistic spectrum disorders. We have postulated that approach
      avoidance motivational conflict (Richer) is the primary factor impeding the
      development of affective communication and have focused therapeutic intervention
      on this perspective. RESULTS: As a result, attachment behavior was markedly
      improved in children, but affective communication with their mothers was not.
      Examing the mothers' images of themselves in infancy in mother-infant
      psychotherapy, problems that the mothers had themselves in infacy with attachment
      behavior to their own mothers affected the mothers' internal representation of
      their children, leading to active evolution of mother-child interaction and
      development of affective communication between the mother and child. CONCLUSIONS:
      In this context, the basis and significance of the internal representation of
      both parties being determinants in the quality of mother-child communication are
      discussed. Our goal in early intervention is not the elevation of a child's
      linguistic-cognitive abilities, but the creation of a comforting relationship in
      which both parent and child can live securely, without strain.

PMID- 11285083
TI  - Executive function in traumatic brain injury and obsessive-compulsive disorder:
      an overlap?
AB  - Thirteen individuals with traumatic brain injury, 13 individuals with obsessive
      compulsive disorder (OCD) and 10 normal controls were compared on
      neuropsychological measures of executive function. Individuals with a traumatic
      brain injury performed significantly poorer than the other two groups on a test
      measuring visuo-spatial strategy. Although the traumatic brain injury group made
      more errors on a test of maze learning and the OCD group less than the control
      group, this did not reach statistical significance. No support for an overlap in
      executive dysfunction in traumatic brain injury and OCD was found. It may be that
      the 'error prevention system' in the brain was influenced in a contrasting way by
      executive dysfunction in these disorders. This difference may reveal itself
      clinically in impulsivity/perseveration and slowness, respectively. Further
      studies were needed to test this hypothesis.

PMID- 11285084
TI  - No evidence of an association between CYP2D6 polymorphisms among Japanese and
      dementia with Lewy bodies.
AB  - Dementia with Lewy bodies (DLB) is the second most frequent degenerative dementia
      among the elderly, following Alzheimer-type dementia (ATD). An association of DLB
      with CYP2D6*4, one of the cytochrome P450IID6 (debrisoquine 4-hydroxylase;
      CYP2D6) gene polymorphisms, was reported previously, but this is controversial.
      Moreover, these reports have been restricted to Caucasian populations. Therefore,
      we compared frequencies of CYP2D6*3, *4, and *10 mutant alleles in 17 Japanese
      DLB patients to those among Alzheimer-type dementia (ATD) patients and healthy
      controls. Polymerase chain reaction amplification and restriction fragment length
      polymorphism analyses were used for genotyping. No significant difference of
      genotype or mutant allele frequencies was detected between DLB, ATD, and healthy
      controls. The present results do not support the suggestion that the CYP2D6 gene
      is related to DLB susceptibility, at least in the Japanese population.

PMID- 11285085
TI  - Neurocutaneous melanosis and psychosis: a case report.
AB  - The paper describes a case of neurocutaneous melanosis (NM), with mental
      retardation, chronic psychosis, and epilepsy possibly due to a temporal focus.
      This is the first report of NM associated with a severe and chronic psychosis. It
      is likely that such an association has not previously been described because of
      the ominous prognosis of most cases of NM with early involvement of the central
      nervous system.

PMID- 11285086
TI  - High levels of nocturnal activity in children with attention-deficit
      hyperactivity disorder: a video analysis.
AB  - Sleep disturbances can lead to symptoms of attention-deficit hyperactivity
      disorder (ADHD) in children. In the present study, we compared the sleep patterns
      of 30 children with ADHD, with those of 19 controls matched for age (5-10 years)
      and sex. Sleep patterns were recorded during one night, using polysomnography
      (PSG) and a video system in the sleep laboratory. Both ADHD children and controls
      were medication free and showed no clinical signs of sleep and alertness
      problems. An infrared camera was used to record all types of movement, which were
      scored and analyzed using specific software (Observer(R) 3.0; Noldus
      International, The Netherlands). No significant differences in sleep variables
      were found between ADHD children and controls. Polysomnography data showed no
      significant difference between the two groups. Attention-deficit hyperactivity
      disorder children moved more often than controls (upper limbs, P < 0.04; lower
      limbs, P < 0.03; all types, P < 0.003). The duration of movements was
      significantly longer in ADHD children (upper limbs, P < 0.03; all types, P <
      0.02). The results of the video analysis were consistent with previous findings
      that ADHD children have higher levels of nocturnal activity than controls. This
      activity concerned mostly upper and lower limb movements. Futher studies are
      required to determine why noctural activity does not affect sleep continuity in a
      more significant way and whether it should be treated specifically.

PMID- 11285087
TI  - Stimulus dose titration for electroconvulsive therapy.
AB  - Stimulus dose titration for electroconvulsive therapy (ECT), the method to
      determine seizure threshold accurately, has not been commonly practiced. We
      describe our early experience of dose titration in 22 Chinese patients and
      compare seizure thresholds measured by dose titration with values predicted by
      the formula-based 'half-age' METHOD: Seizure thresholds, as measured by dose
      titration, varied fourfold among our sample and the average value was 105.5 mC or
      16.7 J. At the titration session, 27% of patients had seizures after a single
      stimulation and 37% had seizures after two stimulations. Only one patient
      required four stimulations to induce a seizure. No patient had significant
      adverse events associated with the dose titration procedure. The 'half-age'
      method in average overestimated seizure thresholds by 44% when compared with that
      measured by dose titration and in 23% of our sample, the overestimation was more
      than 100%. The pros and cons of dose titration and 'half-age' prediction method
      will be discussed. Our early experience suggests that dose titration could be
      performed in the majority of patients receiving ECT.

PMID- 11285088
TI  - The Japanese version of the Barratt Impulsiveness Scale, 11th version (BIS-11):
      its reliability and validity.
AB  - No instrument for assessing impulsiveness has been developed in Japan. After
      translating the Barratt Impulsiveness Scale 11th version (BIS-11) into Japanese,
      we investigated reliability and validity in student (n = 34) and worker (n = 416)
      samples. To assess test-retest reliability, the intraclass coefficient between
      test and retest was calculated in the student sample. Internal consistency was
      examined by calculating Cronbach's alpha in the worker sample. To see factor
      validity, we examined by confirmatory factor analysis whether the three-factor
      model, proposed by a previous report, fit the data. The results showed that the
      Japanese version of the BIS-11 had excellent test-retest reliability and
      acceptable internal consistency reliability. In addition, the Japanese version
      was judged to have similar factor structure to the original one. The Japanese
      version of the BIS-11 is a reliable and valid measure and has possible utility
      for assessing impulsiveness.

PMID- 11285089
TI  - Relation of apolipoprotein E polymorphism to clinically diagnosed Alzheimer's
      disease in the Korean population.
AB  - The gene for human apolipoprotein E (APOE) is found on the long arm of chromosome
      19 (19q13.2) and exists in three common allelic forms, epsilon2, epsilon3, and
      epsilon4. The APOE epsilon4 allele is overrepresented in Alzheimer's disease (AD)
      and is accepted as a genetic risk factor. Some studies reported a protective
      effect of the APOE epsilon2 allele for AD. However, there are some ethnic
      variations in the proportion of different APOE alleles and their relationship to
      AD. We examine the distribution of APOE alleles from 30 AD patients and 158
      controls in Korea. The control subjects were all cognitively intact unrelated
      Koreans. The frequencies of APOE alleles in AD patients were 18.3% (epsilon2),
      58.3% (epsilon3), and 23.3% (epsilon4). The corresponding frequencies in controls
      were 13.3% (epsilon2), 72.5% (epsilon3), and 14.2% (epsilon4). The frequency of
      the APOE epsilon2 allele in AD patients was not significantly different from that
      in controls. When statistical analysis was conducted after the exclusion of the
      APOE epsilon2 allele, the frequency of the APOE epsilon4 allele in AD patients
      was significantly higher than that in controls (P < 0.05). These results support
      that the APOE epsilon4 allele plays a role as a risk factor for AD in Koreans and
      suggest that the APOE epsilon2 allele may not play a protective role in the
      development of AD in Koreans.

PMID- 11285090
TI  - Magnetic resonance imaging findings in patients with delusional disorder due to
      diffuse cerebrovascular disease: a report of seven cases.
AB  - Delusions associated with cerebrovascular diseases have been sporadically
      reported. Although both psychiatrists and neurologists attempted to link
      delusions with anatomical locations of the brain lesion, comorbid psychiatric and
      neurological disorders make the interpretation of delusions difficult. The
      purpose of the present paper is to report the clinical features and magnetic
      resonance imaging (MRI) characteristics in patients with delusional disorder due
      to diffuse cerebrovascular diseases, and to redefine the concept of 'vascular
      delusion'. The clinical features and MRI findings were reviewed retrospectively
      in a series of seven patients with 'delusional disorder due to cerebrovascular
      disease' as defined in Diagnostic and Statistical Manual of Mental Disorders
      (DSMIV). The average age of onset is 64. No patient had a prior personal or
      family history of major psychiatric illness. The illness is presented as acute,
      subacute or stepwise course. Hypertension was present in all patients. Two had
      diabetes mellitus, and one had atrial fibrillation. Three had clinical evidence
      of previous cerebrovascular attacks, only one showed minor neurological deficits.
      Three had diffuse cortical slow wave in electroencephalogram. No patient had
      significant cognitive impairment but had multiple cortical and subcortical
      cerebrovascular lesions in MRI, with white-matter lesions (WML) in bilateral
      frontal areas. Delusional disorder due to diffuse cerebrovascular change is
      characterized by late-onset, stepwise course, and comorbid medical and
      neurological diseases. The results of vascular changes in the present study did
      not establish a cause-effect relationship and should be considered as
      multifactorial in pathogenesis. The findings suggested the hypothesis of neural
      circuit theory. Further studies in larger numbers of patients and newer
      neuroimaging techniques are needed to expand the knowledge learned from these
      findings.

PMID- 11285091
TI  - Panic disorder cases in Japanese-Brazilians in Japan: their ethnic and cultural
      confusion.
AB  - The comparatively high salaries made in Japan are attractive to many Japanese
      Brazilians. The number of individuals from this ethnic group being treated in
      Japanese mental hospitals has increased. We hypothesized that Japanese-Brazilian
      patients with panic disorders adjusted better to Japanese society and culture
      than those with other mental disorders. The subjects in the present study are 40
      Japanese-Brazilian patients undergoing treatment at the Department of Psychiatry
      at Jichi Medical School, Japan, from May 1990 to September 1998. Patients were
      divided into a panic disorder group, a schizophrenic group, a mood disorder group
      and a neurosis group. Demographic data (Japanese language ability, duration of
      residence in Japan etc.) were collected. A comparison was made among the four
      groups. Patients in the panic disorder group showed a significant tendency to be
      fluent speakers of Japanese. Patients in the panic disorder group also had been
      in Japan for a significantly longer period of time than those in the other three
      groups. Japanese ability and length of residence in Japan rule out exacerbating
      factors due to a foreign living environment. Panic disorder patients usually have
      resolved the problems inherent in living and working in a foreign country. In
      general, Japanese-Brazilians are more comfortable both financially and socially
      in Japan than other foreign laborers because of their cultural and family
      background. The emotional conflict experienced by such patients may result from
      concern over whether to live in Brazil or Japan in the future. Their ethnic and
      cultural identity may be confused, fluctuating between identifying with Brazil
      and with Japan, and this may cause vague feelings of anxiety.

PMID- 11285092
TI  - Borderline personality traits in hysterical neurosis.
AB  - The objective of the present study is to demonstrate the traits of the
      psychopathology of Borderline Personality Disorder (BPD) compared with hysterical
      neurosis. A total of 48 subjects with BPD and 40 subjects with hysterical
      neurosis both defined by DSM-III-R were assessed by Diagnostic Interview for
      Borderlines (DIB). Statistical analysis was done by quantification of the second
      type, a multivariate data analysis. The total scores of DIB were BPD group, 6.13
      +/- 1.52; hysterical neurosis group, 4.9 +/- 2.12 (t = 3.05, P = 0.0016). The
      correlation ratio (index of to what extent the two groups are discriminated) was
      0.2442. Among the four parameters of: (i) affect, (ii) cognition, (iii) impulse
      action pattern, (iv), and interpersonal relationships, the partial coefficient
      correlations of (iii) and (iv) were significantly high (0.342, 0.287, P < 0.01).
      The question items with high independent coefficients were manipulation (0.4416),
      intolerance of aloneness (0.3797), demanding nature (0.3768), self-mutilation
      (0.3609), visual hallucination (0.3395). Those with low score of independent
      coefficients were counterdependency (0.0533), identity disturbance (0.1010),
      depression (0.1551), loneliness (0.1752), hypomanic episode (0.1936). Both of BPD
      and hysterical neurosis groups were not so fairly well discriminated. However,
      these results suggested that impulse-action pattern and disorder of interpersonal
      relationships were traits of borderline personality disorder. We could admit
      manipulation, intolerance of aloneness as its symptoms. In addition,
      counterdependency, identity disturbance were comparatively common to both. There
      were some borderline personality traits symptomatically in hysterical neurosis.

PMID- 11285093
TI  - Study of anticipation in Chinese families with schizophrenia.
AB  - The anticipation phenomenon is an important aspect in several genetic disorders
      in which the age at onset (AAO) decreases and the severity of illness increases
      in successive generations. This phenomenon has been reported in several
      schizophrenic family studies, and expanded repeat mutations are implicated. In
      the present study, we investigate the anticipation phenomenon in Chinese
      schizophrenic families. We compare the AAO between two generations of 38
      unilinear schizophrenic families. Intergenerational comparisons show that the AAO
      was significantly earlier in the offspring generation (mean AAO, 22.2 years) than
      that in the parental generation (mean AAO, 31.0 years) (P < 0.001). When only
      including the offspring generation who married, the AAO difference between the
      two generations was not significant (28.4 years vs 31.0 years, P = 0.151). Our
      findings suggest that a selection bias in the parental group might greatly impact
      the study of anticipation in schizophrenia. Other unavoidable biases associated
      with these analyses are discussed in the text.

PMID- 11285094
TI  - Sociomedical aspects of epileptic patients: their employment and marital status.
AB  - We examined the employment and marital status of adult patients with epilepsy who
      did not have mental retardation and who had been treated at Hirosaki University
      Hospital, Hirosaki, Japan, for more than 5 years. The present study included 278
      patients (142 males and 136 females) ranging from 20 to 60 years of age. We
      investigated the occupational status of the subjects and found that 168 had
      permanent jobs, but 41 patients were unemployed at the time of this survey. The
      proportion of the patients whose seizures were controlled at the time of this
      survey was 68% (114/168) in the group having permanent jobs, and 22% (9/41) in
      the unemployed group. Forty cases answered that they had resigned from their jobs
      due to occurrence of epileptic seizures. Of these patients, 13 were dismissed and
      27 resigned voluntarily due to the potential for seizures. As to relationship
      between jobs and neuropsychiatric complications, the incidence of a past history
      of psychotic states in the unemployed group was significantly higher than that in
      the employed group. As to marital status, 13 males and 16 females (n = 29) had
      experienced divorce. Seven cases (two males and five females) had answered that
      epilepsy had been the reason for their divorce. We conclude that epilepsy or
      epileptic seizures have various negative effects on the patient's social life.

PMID- 11285095
TI  - Sociodemographic and clinical characteristics of psychiatric patients coercively
      brought to hospitals.
AB  - In order to clarify the sociodemographic and clinical characteristics of
      psychiatric patients with poor motivation for treatment, we examined patients who
      were coercively brought to hospitals. Sociodemographic and clinical data on 287
      inpatients from two private psychiatric hospitals in Japan were retrospectively
      analyzed. All patients were in the hospitals on 1 April 1997 and had received
      treatment prior to this admission. Of these inpatients, 67 (23.3%) were
      coercively brought to hospitals. Multiple logistic regression was performed on
      the data of these patients to identify the factors associated with their
      resistance to visiting the hospital. From the results of multivariate analysis,
      four characteristics were associated with patients coercively brought to
      hospitals, namely medication compliance, receiving regular outpatient treatment
      or not, a history of self-aggression or aggressive behavior towards others, and
      living arrangements. For patients who had lived with relatives before
      hospitalization, the primary caregiver being a parental caregiver was associated
      with patients coercively brought to hospitals, although it was not statistically
      significant. In addition, agitation was associated with patients not coercively
      brought to the hospital according to multivariate analysis. The present results
      suggest that psychiatric patients with poor motivation are more likely to have
      poor medication compliance, to have not received regular outpatient treatment, to
      have a history of aggressive behavior and to live alone. For patients who lived
      with their caregivers prior to hospitalization, poorly motivated patients tended
      to have parental caregivers and were less likely to be agitated.

PMID- 11285096
TI  - Postexercise facilitation appears durable in normal subjects.
AB  - Transcranial magnetic stimulation (TMS) was used to study the postexercise
      facilitation of 11 normal subjects on eight occasions. Between individuals, there
      was almost a sixfold difference in facilitation. The greatest positive percentage
      change for any individual was 61%, and the greatest negative percentage change
      was 51%. The results suggest that facilitation is a durable individual
      characteristic of normal subjects. Serial studies may therefore be indicated in
      monitoring individuals suffering relapsing conditions.

PMID- 11285097
TI  - Effective treatment of aggression and impulsivity in antisocial personality
      disorder with risperidone.

PMID- 11285098
TI  - Treatment and 9-year outcome of butane-induced psychotic disorder in a butane
      dependent Japanese male adolescent.

PMID- 11285099
TI  - Influence of earthquake on the quality of life of patients with type 1 diabetes.

PMID- 11285100
TI  - To tickle your fancy.

PMID- 11285101
TI  - Prevention of smoking behaviors in middle school students: student nurse
      interventions.
AB  - This article examines the use of the Tar Wars curriculum with the public health
      problem of preteen smoking and outlines interventions with a middle school
      population by community health student nurses from a state university. Smoking is
      the single most preventable cause of death and disability. Three million people
      die worldwide each year as a result of smoking. Cigarette smoking has now been
      labeled a pediatric disease. Estimates are that 3,000 children will begin a
      lifelong addiction to cigarettes every day. They will face a life of poor quality
      based on the medical consequences of smoking cigarettes. Mortality from tobacco
      use is annually greater than that from drug abuse, AIDS, suicide, homicide, and
      motor vehicle accidents combined. Preteen and teenage smoking is now a public
      health problem, therefore implications for service learning, nursing advocacy,
      and interventions with this health problem are discussed.

PMID- 11285102
TI  - Adolescent health behaviors and related factors: a review.
AB  - This review examined research relevant to adolescent health behavior in order to
      identify key behaviors and factors related to behaviors for targeting health
      promoting interventions. The 34 studies reviewed sampled mainly Caucasian
      subjects ranging in age from 12 to 24 years. The majority of the studies were
      descriptive and cross-sectional, and they dealt with a specific health behavior
      or group of behaviors such as eating, sleeping, and exercise. Primary factors
      related to health behavior included gender, family structure, ethnicity,
      knowledge, and attitudes. Increased knowledge of factors that impact adolescent
      health behaviors is essential so that public health nurses (PHNs) and other
      health professionals can be more responsive to developmental and lifestyle
      factors influencing the health of youth within families and communities.

PMID- 11285103
TI  - Scores on the Nursing Child Assessment Teaching Scale for father--toddler dyads.
AB  - Fathers of 49 Canadian children (ages 13 to 24 months) were observed interacting
      with their child at home using the Nursing Child Assessment Teaching Scale
      (NCATS). Consensus ratings from two observers were used in the analysis. Compared
      with the NCATS reference data for 164 mothers of similar ethnicity and marital
      status with similar-aged children, mothers were more responsive than fathers in
      the interactions. Mothers had significantly higher scores on the overall Total
      NCATS score, on the Total Parent score, and on the Parent Contingency score than
      the fathers. In contrast, children were more responsive to fathers than mothers.
      Children interacting with their fathers had significantly higher Total Child
      scores and higher Child Contingency scores than those interacting with their
      mothers. Maternal and paternal age and education were not correlated to scores on
      the NCATS. Implications for practitioners are discussed and the results are
      compared to a study of mothers and fathers interacting with children ages 2 to 12
      months old in which the observations were measured by the NCATS. Results suggest
      that NCATS cutoff scores used to identify mothers in need of intervention should
      be used with caution for father--toddler interactions.

PMID- 11285104
TI  - Mentoring benefits and issues for public health nurses.
AB  - New public health nurses (PHNs) move from novice to expert status with enormous
      expectations from their organization, their peers, and themselves. These
      expectations lead to stress that may be beyond the level of endurance. Mentoring
      is an important answer to this problem. Mentoring is the greatest gift PHNs can
      give to each other, especially for PHNs who self-identified themselves as
      minority cultural group members. This article describes definitions, roles,
      benefits, and responsibilities of mentors and mentees and includes mentoring
      concerns, current and proposed mentoring programs, and mentoring issues for
      gender and race. Organizational mentoring programs can be created that will
      facilitate the development of mentoring relationships. These programs help
      experienced PHNs bridge the gap between the theory and reality of nursing for
      themselves and inexperienced colleagues.

PMID- 11285105
TI  - Occupational health nurses' work and expertise in Finland: occupational health
      nurses' perspective.
AB  - The purpose of this study was to describe Finnish occupational health nurses'
      (OHNs) work in terms of its contents, characteristics, necessities, meanings,
      development areas, changes, and expertise. The data were gathered via essays
      handwritten by OHNs (n = 20). Qualitative content analysis revealed that
      occupational health nursing practice included work with individuals, work
      communities, and various collaborative partners, office tasks, and other duties.
      Responses about OHNs' work were classified as characteristics of OHNs and of
      their work with advantages as well as disadvantages. The work of OHNs requires a
      multidisciplinary knowledge basis, professional skills, certain personal
      characteristics, and other features. These should be maintained and developed
      through continual education. The outcomes of OHNs' work were better health and
      healthier habits for employers, higher productivity for employers and
      occupational health care units, and health care savings for society. The most
      significant change that has occurred over the last 20 years was the move from an
      individual and medicine orientation toward a focus on the work community and on
      nursing. Expert OHNs were expected to be competent and multiskilled professionals
      who apply multidisciplinary knowledge in practice. This study brought out the
      need for further study with a focus on the client's perspective.

PMID- 11285106
TI  - Home hygiene practices and infectious disease symptoms among household members.
AB  - Public health programs are generally targeted to communitywide, population-based
      prevention strategies, with little attention focused on the home environment as
      one potential source of transmission of infectious diseases. The purpose of this
      correlational prevalence survey was to describe the relationship between home
      hygiene practices and prevalence of infectious disease symptoms among household
      members. Three hundred and ninety-eight households with 1,662 members in an inner
      city population (96.4% Hispanic) were surveyed to examine hygiene practices and
      determine the presence of transmission of infection, defined as the presence of
      the same symptom(s) in two or more household members for which at least one
      individual sought medical attention and received treatment. At least one
      individual in 78.6% of households reported symptoms of infection in the previous
      30 days, and 37.9% of households met the definition of disease transmission. In
      univariate analyses, five factors were significantly associated with risk of
      household transmission, but in the logistic regression model, only use of
      communal laundry (p = 0.009) and lack of bleach use (p = 0.04) were significantly
      predictive of increased risk of transmission. This is the first comprehensive
      survey of home hygiene practices and the first study to identify a potential link
      between laundry and risk of disease transmission in homes. This potential link
      warrants further study in clinical trials.

PMID- 11285107
TI  - Defining risk in home visiting.
AB  - Risks associated with home visiting have been acknowledged in the nursing
      literature since the 19th century, yet there is not a well-defined body of
      literature on this subject. This void in the literature needs to be addressed in
      view of the current emphasis on practice in the community and the increase in the
      number of nurses and other health professionals that are new to the field who
      currently make visits. This article explores how different disciplines define
      risk and risk taking, identifies attributes of those who become involved in risk
      situations, and proposes the Cognitive-Perceptual Model of Risk in Home Visiting
      (CPMRHV) for community and public health nursing. The CPMRHV model provides a
      framework for identifying how field workers (FWs) perceive, assess, and evaluate
      situations relative to risk and suggests the development of policies and
      procedures to empower them and to assure the quality of care.

PMID- 11285108
TI  - The psychosocial impact of interactive computer use within a vulnerable elderly
      population: a report on a randomized prospective trial in a home health care
      setting.
AB  - Quality of care for vulnerable elderly clients makes it important to consider the
      psychosocial effects of interactive computer use as a means to communicate for
      social, functional, and/or health care purposes in a home health care setting. In
      a 3-month randomized prospective trial, telecommunications terminals were
      installed in the private residences of computer-illiterate persons, 65-years-of
      age and older, providing visiting nurses the opportunity to teach computer use
      with three different training methods. The control group had similar weekly nurse
      visits, but no computer terminal use. Pre-posttests using the Rosenberg Self
      Esteem Scale and the Geriatric Depression Scale compared change in self-esteem
      and depression scores of computer-use clients with the scores of the control
      group clients. Interactive computer use, alone, did not significantly change
      scores. Compared to the control group, however, there was a significant change
      toward improved self-esteem and depression when interactive computer use was
      accompanied with weekly nurse computer training. Weekly training with a
      significant other, as a substitute for the nurse trainer, significantly improved
      self-esteem scores but not depression scores. Interactive computer use was not
      associated with decreased self-esteem or increased depression. Attitude changes
      and responses to the particular telecommunication service used in this study were
      mixed, suggesting future research should be based on improved telecommunication
      systems with access to programs that have greater practical application to the
      needs of elderly clients.

PMID- 11285110
TI  - Fc-signalling in the modulation of immune responses by passive antibody.
AB  - Passive antibody can both suppress and augment immune responses. Until recently,
      there was virtual unanimity on the importance of the interaction of the Fc
      portion of modulating antibody with Fc-receptors (Fc-signalling), especially in
      experiments involving the suppression by antibody. Experiments reported in the
      last few years, that do not demonstrate the range of Fc-portion/Fc-receptor
      influences on the suppression of immune responses by passive antibody, have
      introduced new uncertainty into this field. The purpose of this paper is to
      review how the initial controversy on the influence of Fc-signalling in
      inhibition by passive antibody was resolved. Old and new approaches are suggested
      that may help in resolving the current uncertainty engendered by recent
      experimental results that were interpreted to mean that passive suppressive
      antibody does not utilize the inhibitory FcgammaRIIB receptor. An understanding
      of the factors that influence negative Fc-signalling is needed in order to
      optimize clinical therapies whose action depends on the suppressive property of
      antibody.

PMID- 11285111
TI  - No evidence for a role of FcgammaRIIB in suppression of in vivo antibody
      responses to erythrocytes by passively administered IgG.

PMID- 11285112
TI  - Current concepts of the mechanisms of antibody suppression are not compatible
      with contemporary knowledge of lymphocyte activation.

PMID- 11285114
TI  - Validity of the two-signal model for activation of CD28-deficient T lymphocytes:
      quantitative characterization of an alternative costimulatory function of
      dendritic cells.
AB  - The observation that primary T-dependent immune responses are generated in mice
      lacking CD28, the only receptor definitively shown to costimulate naive T cells,
      has led to ambiguity as to whether costimulation is absolutely required for
      initiation of T-cell responses. In this report, in vitro analysis of the
      relationship between cell density and proliferation demonstrates that activation
      of CD28-/- T cells to immobilized T-cell receptor (TCR)-alpha monoclonal
      antibodies (MoAb) depends on costimulatory signals provided by other cells in
      culture and occurs only at cell densities sufficient to permit these
      intercellular interactions. These signals are necessary even under TCR triggering
      conditions that obviate the CD28 requirement. Dendritic cells (DCs) provide the
      necessary costimulation in vitro and prime T cells in vivo in CD28-/- mice.
      Single-cell and limiting dilution analyses indicate that individual T cells from
      normal and CD28-/- mice produce equivalent interleukin (IL)-2 in response to DCs.
      However, half as many T cells produce IL-2 when only the CD28-independent pathway
      is used. Nonetheless, CD28-/- T cells produce sufficient IL-2 to support clonal
      expansion comparable to that of CD28+/+ T cells, which may account for the
      equally robust in vivo responses initiated by DCs in normal and CD28-deficient
      animals.

PMID- 11285115
TI  - Identification and design of p53-derived HLA-A2-binding peptides with increased
      CTL immunogenicity.
AB  - The replacement of a suboptimal amino acid in a primary anchor position with an
      optimal residue improves human leucocyte antigen (HLA) binding and
      immunogenicity, while maintaining cytotoxic T lymphocyte (CTL) specificity. Using
      a neural network capable of performing quantitative predictions of peptide
      binding to HLA-A2 molecules, we identified three p53 protein-derived nonamer
      peptides with intermediate binding owing to suboptimal amino acids in the P2
      anchor position. These peptides were synthesized along with the corresponding
      analogs, where the natural P2 residue had been replaced with the optimal leucine
      residue. All three modified peptides bound to and more efficiently stabilized HLA
      A2 molecules than the corresponding nonmodified peptides. The HLA-A2 transgenic
      mice were used for immunization. Two of the epitopes were more immunogenic in
      their modified than in their natural versions. The CTLs raised against the
      modified peptides efficiently killed the target cells pulsed with the
      corresponding native peptide. In terms of sensitizing the targets cells for the
      CTL killing, the modified peptides were more efficient than native peptides.
      Finally, the CTLs induced by modified peptide killed HLA-A2 transgenic mouse
      fibrosarcoma cells transfected with human p53 DNA. The data suggest that modified
      self-peptides derived from overexpressed tumour-associated proteins can be used
      in vaccine development against cancer, and that quantitative predictions of HLA
      binding is of value in the rational selection and improvement of target epitopes
      recognized by CTLs.

PMID- 11285116
TI  - Characterization of the early antibody response in bovine tuberculosis: MPB83 is
      an early target with diagnostic potential.
AB  - A 26-kDa antigen has been shown to be a dominant antibody target in Mycobacterium
      bovis-infected cattle. In this study, that antigen was used as an immunogen to
      raise a panel of mouse monoclonal antibodies. The majority of those bound to
      native protein with a molecular mass of 26 kDa and to recombinant MPB83, strongly
      suggesting that MPB83 is an important B-cell antigenic target in bovine
      tuberculosis. In order to provide assessment of the potential of measuring
      antibody responses to the native protein, one monoclonal antibody, 1F11, was
      incorporated into an enzyme-linked immunosorbant assay format to trap antigen
      from a crude bacterial extract. Despite some disadvantages of this format, serum
      samples from cattle which had been infected experimentally with M. bovis, and
      from tuberculin skin-test-negative and -positive field cattle were tested for the
      presence of antibodies. Data from the skin-test-negative cattle allowed an
      arbitrary cut-off value to be established and, under these conditions, test
      sensitivity and specificity were estimated at 37.5 and 89%, respectively. These
      results indicate potential for MPB83 in the development of assays for serological
      diagnosis of bovine tuberculosis.

PMID- 11285117
TI  - Differences in the reactivity of CD4+ T-cell lines generated against free versus
      nucleosome-bound SV40 large T antigen.
AB  - Previous results have revealed a strong correlation between polyomavirus BK
      reactivation and disease activity and antinuclear auto-antibody production in the
      human autoimmune disease systemic lupus erythematosus. BK virus establishes a
      latent infection in most humans, and reactivation requires the production of the
      DNA-binding large T antigen. Experimentally induced expression of the
      polyomavirus SV40 large T antigen in mice induces both an immune response to
      large T antigen and autoimmune response to nuclear antigens and antinuclear
      antibody production. Previous results have indicated that human T-antigen
      specific CD4+ T-cell lines are stimulated equally by free, soluble and nucleosome
      bound T antigen. This study was designed to determine how antigen processing of
      nucleosomes containing bound SV40 large T antigen may affect the specificity and
      response characteristics of experimentally induced T-antigen-specific CD4+ T
      cells. The results indicated that CD4+ T-cell lines generated from mice immunized
      with soluble, free T antigen responded very poorly in response to stimulation
      with T antigen bound to nucleosomes. CD4+ T-cell lines generated from mice
      immunized with nucleosomes that had bound T antigen in situ responded to both
      free and nucleosome-bound T antigen. The T-antigen-specific, CD4+ memory T cells
      induced by latent polyomavirus infections in humans may be uniquely suited to
      initiate autoimmunity to nuclear antigens upon virus reactivation.

PMID- 11285118
TI  - IgE-mediated suppression of primary antibody responses in vivo.
AB  - The ability of immunoglobulin (Ig)G to feedback suppress antibody (Ab) responses
      is a well known property clinically used to prevent haemolytic disease of
      newborns. We recently found that IgG was able to suppress the primary Ab response
      to sheep red blood cells (SRBC) in mice lacking the known Fc-receptors for IgG.
      In addition, IgE and F(ab')2 fragments of IgG were able to suppress the response
      to SRBC in wild-type mice. These results suggested that the IgG-mediated
      suppression can take place independently of the IgG (Fc) portion and that masking
      of the epitopes is an important mechanism. In the present report we investigated
      whether the suppression caused by IgE is Fc-dependent. Monoclonal IgE anti-2,4,6
      trinitrophenyl (TNP), administered with TNP-coupled SRBC (SRBC-TNP), can induce
      an efficient suppression in mice lacking FcgammaRI + RIII + FcepsilonRI (owing to
      the lack of the common gamma chain, FcRgamma), FcgammaRIIB or FcepsilonRII
      (CD23). Because the known IgE-binding receptors are FcepsilonRI, CD23,
      FcgammaRIIB and FcgammaRIII, the results suggest that also the IgE-mediated
      suppression can take place independently of the Fc-receptors. A slightly less
      efficient suppression in CD23-deficient animals, suggests a minor involvement of
      this receptor.

PMID- 11285119
TI  - Alternatively activated macrophages differentially express fibronectin and its
      splice variants and the extracellular matrix protein betaIG-H3.
AB  - Alternative activation of macrophages, induced by Th2 cytokines and
      glucocorticoids, is essential for the proper functioning of anti-inflammatory
      immune reactions. To this end, alternatively activated macrophages (aaMPhi)
      express a not yet fully unravelled set of genes including cytokines such as
      alternative macrophage activation-associated CC-chemokine (AMAC)-1 and pattern
      recognition molecules such as the scavenger receptor CD163. In order to further
      characterize the molecular repertoire of aaMPhi, differential gene expression was
      analyzed by combining subtractive suppression cloning and differential
      hybridization. We show here that aaMPhi induced by interleukin (IL)-4 overexpress
      the prototype extracellular matrix (ECM) protein fibronectin on the mRNA and
      protein level. This overall increase is accompanied by a shift in fibronectin
      splice variants from an embryonic to a mature pattern. In addition, the
      expression of another ECM protein, betaIG-H3, is also upregulated by IL-4 in
      aaMPhi. In contrast to IL-4 and in line with its inhibitory effect on wound
      healing, dexamethasone exerts a strongly suppressive effect on fibronectin and
      betaIG-H3 expression. In conclusion, overexpression of ECM proteins induced by IL
      4 in macrophages suggests that aaMPhi may be involved in ECM deposition and
      tissue remodelling during the healing phase of acute inflammatory reactions and
      in chronic inflammatory diseases.

PMID- 11285120
TI  - Binding, trafficking and accumulation of serum amyloid A in peritoneal
      macrophages.
AB  - Murine serum amyloid A1.1 (SAA1.1) has been conjugated with the fluorophore Texas
      Red (TxR), and its interaction with peritoneal macrophages has been visualized by
      scanning confocal microscopy. Binding of TxR-SAA to cell surfaces was inhibited
      by an excess of unlabelled SAA indicating the involvement of saturable receptors.
      Internalized TxR-SAA was seen initially as small punctate signals which in some
      cells evolved into a fine fluorescent network, a pattern typical of tubular
      endosomes. Colocalization of TxR-SAA with Cy5-labelled low density lipoprotein
      (LDL) but not with Oregon Green-labelled transferrin suggested that SAA
      trafficked through endosomes and lysosomes for degradation rather than through
      recycling compartments. Consistent with this catabolic pathway, macrophages
      loaded with TxR-SAA lost fluorescence within several days after being shifted to
      a fluorophore-free medium. In sharp contrast to this, cells maintained under
      amyloid-forming conditions, i.e. in the presence of unlabelled SAA and amyloid
      enhancing factor (AEF) before and after treatment with TxR-SAA, remained brightly
      fluorescent over the course of 5 days. Immunocytochemistry verified the
      accumulation of SAA within macrophages. These findings support the hypothesis
      that a decreased catabolism of internalized SAA plays a role in AA amyloid
      pathogenesis.

PMID- 11285121
TI  - Induction in mucosa of IgG and IgA antibodies against parenterally administered
      soluble immunogens.
AB  - The induction of a mucosal immunity provides an additional principle of
      vaccination by preventing the entry of pathogens in the body. Albeit the fact
      that intensive research has been conducted on local vaccines, the major mucosal
      vaccine commercially available for human use remains the oral polio vaccine. We
      have previously demonstrated that parenteral vaccination in humans with tetanus
      toxoid (TT) results in a genital immunoglobulin (Ig)G antibody (Ab) response.
      Here, we show that injections of TT with no adjuvant induces an anti-TT response
      in the mucosal tissues of normal BALB/c mice. The response is multiregional,
      involves both IgG and IgA isotypes, and is long-lasting. Similarly, injections of
      haptens coupled to TT or to other diffusible proteins may induce mucosal Abs.
      These results led us to immunize normal BALB/c mice with a viral peptide coupled
      to TT by disulfide bridging. The hapten was a 17 amino acid peptide containing
      the ELDKWA sequence of human immunodeficiency virus (HIV)-1 gp41. A significant
      IgG and IgA Ab response to the immunizing peptide was induced in various mucosal
      tissues despite the presence of a suboptimal Ab response in the spleen. The
      results indicate that mucosal immunity to peptides that are candidates for human
      vaccinations may be achieved by parenteral adjuvant-free immunization with
      peptide coupled to TT.

PMID- 11285122
TI  - C1qRp elicits a Ca++ response in rat NK cells but does not influence NK-mediated
      cytotoxicity.
AB  - The cell surface receptor C1qRp (receptor for C1q, regulating phagocytosis)
      present on macrophages and neutrophils, is presumed to stimulate phagocytosis in
      these cells. However, C1qRp is also present on natural killer (NK) cells, and in
      these cells its physiological function is not currently known. We have
      investigated putative functions of this cell surface molecule in rat NK cells
      with the aid of two novel monoclonal antibodies (MoAb) LOV3 and LOV8 against rat
      C1qRp. NK cells are known to be potent cytotoxic effector cells, both through
      specific recognition of ligands on a target cell and killing of antibody-coated
      target cells (antibody-dependent cellular cytotoxicity, ADCC). NK cells
      prestimulated with MoAbs LOV3 or LOV8 did not exhibit altered ADCC. Furthermore,
      the addition of MoAb LOV3 or LOV8 to cytotoxic cultures of NK cells and Fc
      receptor positive tumour cells did not affect killing in a redirected killing
      assay, indicating that the receptor did not influence NK cytotoxicity. However,
      this is the first paper to show that an intracellular Ca++-response is induced in
      rat NK cells upon stimulation of C1qRp with LOV3 and LOV8. The response induced
      by the antibodies was only minimally reduced in the presence of EGTA, indicating
      that most of the response is owing to the Ca++ mobilization from intracellular
      calcium stores.

PMID- 11285123
TI  - Diagnostic and biological significance of anti-p41 IgM antibodies against
      Borrelia burgdorferi.
AB  - We performed a prospective study to investigate the biological significance and
      diagnostic specificity of anti-p41 immunoglobulin (Ig)M antibodies against
      Borrelia burgdorferi. During a 1-year interval 2403 patients were referred to our
      department for B. burgdorferi serology. Sixty-three patients had repetitive
      positive tests for IgM anti-p41 antibodies and negative tests for anti-p41 IgG
      antibodies. Ten of the 63 patients recently had symptoms of erythema migrans. A
      confirmatory IgM Western blot gave a positive reaction in 5 patients out of 53
      patients with little or no clinical evidence of B. burgdorferi infection. The
      remaining 48 patients were negative in this test and were considered as false
      positives. Two whole cell enzyme-linked immunosorbent assay (ELISAs), two
      immunofluorescence assays and Western blotting were not useful as confirmatory
      tests. Sera from 330 blood donors and 72 cord sera were also screened for anti
      p41 IgM. Five blood donor sera and five cord sera showed an IgM reactivity
      against p41. Based on our data we hypothesize that up to 1.5% of the population
      may have natural IgM antibodies against p41 in their sera. We observed that six
      out of nine sera with such antibodies could immobilize a B. afzelii reference
      strain in vitro. Whether anti-p41 IgM antibodies are capable of inactivating
      infective spirochetes and thereby prevent infection in vivo is, however, not yet
      clarified. The paradoxical conclusion that anti-p41 IgM antibodies may be a sign
      of resistance to infection rather than a sign of infection should be given
      consideration.

PMID- 11285124
TI  - Activation of cell-mediated immunity following immunization with pneumococcal
      conjugate or polysaccharide vaccine.
AB  - The immunogenicity of pneumococcal polysaccharide (PS) vaccines can be improved
      by conjugating PS to a polypeptide carrier that alters the immune response from T
      cell independent to T-cell dependent. In order to study the influence of PS or
      protein antigens as inducers of cell-mediated responses, 30 adults were immunized
      with a 23-valent pneumococcal PS vaccine (PS-group) or an 11-valent, tetanus and
      diphtheria mixed carrier conjugate vaccine with (adjuvant group) or without
      aluminium adjuvant (nonadjuvant group). Cell-mediated responses were analyzed on
      days 0, 14 and 28 after vaccination by measuring lymphocyte proliferation and
      production of interferon (IFN)-gamma (Th1 marker) or interleukin (IL)-4 and IL-5
      (Th2 markers) cytokines after in vitro stimulation with the PS and protein
      components of the vaccines. Tetanus and diphtheria proteins were the main
      inducers of lymphocyte proliferative and cytokine responses. Conjugate vaccines
      induced increased proliferative responses to the tetanus or diphtheria protein,
      but not to the PS components. In the PS-group, a lymphocyte proliferative
      response to protein antigens was not observed. The number of antigen-specific and
      nonspecific IFN-gamma-secreting cells detected by ELISPOT tended to increase in
      all three groups in response to protein or to PS antigen. No major differences
      were detected in the number of IL-4-secreting cells measured 14 and 28 days after
      vaccination. The conjugate vaccine with adjuvant was associated with Th2 type of
      activation indicated by an enhanced IL-5 secretion in response to the tetanus and
      diphtheria protein antigens.

PMID- 11285125
TI  - Transracial evidence for the influence of the homologous HLA DR-DQ haplotype on
      transmission of HLA DR4 haplotypes to diabetic children.
AB  - The HLA-DQB1*0302 allele on DR4 haplotypes is a marker for type 1 diabetes
      susceptibility and it is an especially high-risk allele in DR3/4 because of its
      preferential distribution in Caucasian DR3/4 patients. In Asians, not only
      DQB1*0302 but also DQB1*0401 on DR4 haplotypes are associated with type 1
      diabetes. We investigated whether the contribution of these DQ molecules was also
      genotype-dependent in Asians. Although the prevalence of the DR4-DQB1*0302
      haplotype did not differ in patients vs. controls, the DR3/4-DQB1*0302 genotype
      had a RR of 12 (P<10(-4)). Moreover, a significant association of DQB1*0302 with
      the DR3/4 genotype was found (RR=3, P<10(-2)). In contrast, the distribution of
      DQB1*0401 alleles of DR4/X (X: other than 3, 4) is different from that of DR3/4
      and DR4/4. Especially a significant association of DQB1*0401 with DR4/X (X: other
      than 1, 3, 4) was found (RR=3, P<10(-3)). The frequency of transmission of the
      DR4-DQB1*0302 haplotypes to diabetic offspring with DR3 was 80%, while to those
      without DR3 was 40%. In contrast, the transmission of the DR4-DQB1*0401 to those
      with DR3 was 60%, while to those without DR3 was 80%. High-risk DR4 subtypes were
      predominant in DR4/X (RR=7, P<10(-3)), whereas protective DR4 subtypes were
      observed mainly in the DR3/4 (RR=3, P<0.05). The association with diabetes and
      transmission to a diabetic offspring of DR4 haplotypes varies depending on the
      haplotype borne on the homologous chromosome. This might contribute not only to
      the synergistic effect of DR3/4, but also to the susceptibility influence of HLA
      DQB1*0401 alleles confined to DR4/X.

PMID- 11285126
TI  - The origin of Minnan and Hakka, the so-called "Taiwanese", inferred by HLA study.
AB  - The Minnan and Hakka people groups, the so-called "Taiwanese", are the
      descendants of early settlers from the southeast coast of China during the last
      few centuries. Genetically they showed affinities to southern Asian populations,
      as determined by phylogenetic trees and correspondence analysis calculated from
      HLA allele frequencies. This corresponds historically with the fact that they are
      the descendants of the southeast coastal indigenous population (Yueh) of China
      and should therefore not be considered as descendants of "pure" northern Han
      Chinese. A33-B58-DRB1*03 (A33-Cw10-B58-DRB1*03-DQB1*02), the most common HLA
      haplotype among "Taiwanese", with a haplotype frequency of 6.3%, has also been
      found to be the most common haplotype among Thai-Chinese and Singapore Chinese,
      two other populations also originating from the southeast coast of China. These
      observations suggests that this haplotype is the most well-conserved ancient
      haplotype of the Yueh.

PMID- 11285127
TI  - HLA class I and class II allele and haplotype diversity in Martinicans.
AB  - The Martinican population is mainly the product of admixture between African
      people and French Caucasians. The aim of the present study is to investigate at
      the DNA level the polymorphism of HLA class I (HLA-A, HLA-B) and class II (HLA
      DRB1, DQB1 and DPB1) genes in a population of 100 Martinicans. Allelic
      distributions and interlocus linkage disequilibria were compared to those
      observed in a French Caucasian population and in African or North American
      African populations. Our data revealed a higher degree of polymorphism in
      Martinicans than in Caucasians and showed a prominant contribution of African
      origin in the admixed genetic feature of this population. African characteristic
      alleles were significantly represented in Martinicans: A*30, *33 *34, *66, *74,
      *8001, B*1510, *35, *42, *53, DRB1*0302, *0804, *1202, *1304, *1503, DPB1*0101,
      *1701, *1801, *3901. Moreover a higher diversity of A*-B* and DRB1*-DQB1*
      associations was observed in Martinicans compared to Caucasians which also
      reflects the African genetic background of this population. In the whole, using
      PCR-based genotyping methods for HLA class I and class II loci, this study allows
      a preliminary description of HLA allele distribution in this Caribbean island and
      gives new elements which may be helpful in the anthropologic field as well as in
      HLA and disease association studies.

PMID- 11285128
TI  - Distributions of HLA class I alleles and haplotypes in Bulgarians--contribution
      to understanding the origin of the population.
AB  - In this study we present for the first time HLA class I allele and haplotype
      frequencies at DNA level in the Bulgarian population. HLA class I profile of
      Bulgarians has been compared to other European and Mediterranean populations of
      common historical background in order to clarify more precisely the origin of our
      population. Genetic distances, phylogenetic trees and correspondence analyses
      show that the Bulgarian population is more closely related to the Italian, the
      Mediterranean, the Armenian and the Romanian population than to the other East
      and West European population. This is further supported by the analysis of HLA
      class I haplotypes in Bulgarians. Most of them are also common in Europe. However
      their frequency pattern in Bulgarians is similar to the South European
      populations. The presence of some rare alleles and haplotypes indicated Asian
      genetic inflow. On the basis of HLA class I profile and supported by historical
      and anthropological data, we suggest that the Bulgarian population is
      characterized by the features of the Southern European anthropological type with
      some influence of other groups such as Asians, Turks, Armenians. Migrations and
      assimilation of many different ethnic groups are the major factor determining the
      genetic diversity of our population.

PMID- 11285129
TI  - Identification of a novel single-nucleotide polymorphism (Val554Ile) and
      definition of eight common alleles for human IL4RA exon 11.
AB  - The interleukin (IL)-4 receptor alpha chain gene (IL4RA) is a polymorphic gene
      which is reportedly involved in the development of atopy. Of the 14 single
      nucleotide polymorphisms (SNP) reported to date in the coding region of IL4RA, 11
      are positioned to exon 11. This big exon encodes more than two thirds of the
      mature protein, including most of the cytoplasmic region. Here we report the
      identification of a new IL4RA SNP at the first nucleotide of codon 554 (GTA -->
      ATA) in exon 11, leading to an amino acid substitution from Val to Ile (V554I).
      Furthermore, we present complete nucleotide sequence data for eight common
      alleles resulting from combinations of 9 out of the 12 SNP at IL4RA exon 11. Homo
      or heterozygous combinations of these eight alleles accounted for all the IL4RA
      exon 11 genotypes found in Caucasian individuals from our geographical area.

PMID- 11285130
TI  - Validation of DNA-based HLA-A and HLA-B testing of volunteers for a bone marrow
      registry through parallel testing with serology.
AB  - A total of 42,160 individuals were typed for HLA-A and HLA-B by both serology and
      PCR-based typing. The HLA assignments included all of the known serological
      equivalents. The majority of the individuals (99.9%) were from U.S. minority
      population groups. The serologic typing was performed between 1993 and 1997 at
      the time of recruitment for the National Bone Marrow Program (NMDP) registry. The
      polymerase chain reaction (PCR)-based typing was carried out in two phases. In
      phase I, DNA typing was performed by PCR using sequence-specific oligonucleotide
      probes (PCR-SSOP) or PCR using sequence-specific primers (PCR-SSP) without
      knowledge of the serologic assignments. Discrepancies were identified between the
      serologic and DNA assignments in 24% of the volunteers (8% of volunteers differed
      for only HLA-A assignments, 13% for HLA-B, and 3% for both HLA-A and -B) and a
      potential explanation was assigned each discrepant serology/DNA pair. In phase
      II, a random sampling scheme was used to select a statistically significant
      number of individuals for repeat DNA typing from each of these categories. The
      categories included antigens missed by serology, nonexpressed (null) alleles, PCR
      amplification failures, misassignment of antigens and nomenclature issues. Only a
      single individual was found to carry a null allele. DNA-based testing correctly
      typed nearly 99% of the donors at HLA-A, more than 98% at HLA-B, and more than
      97% at both HLA-A and -B validating this methodology for registry typing.

PMID- 11285131
TI  - Case-control study with narcoleptic patients and healthy controls who, like the
      patients, possess both HLA-DRB1*1501 and -DQB1*0602.
AB  - In previous studies, we suggested that the tumor necrosis factor (TNF-alpha and
      its receptor 2 (TNFR2) genes could be associated with the susceptibility to human
      narcolepsy, and that haplotype carrying DRB1*1502 had a negative association with
      the disorder. To further evaluate these associations, we herein compared
      narcoleptic patients with healthy individuals who, like the patients, possessed
      both DRB1*1501 and DQB1*0602. Results agreed with the negative association of
      DRB1*1502 and positive association of the TNF-alpha(-857T) and TNFR2-196R
      combination with the disorder. In addition, a significant association of the TNF
      alpha(-857T) homozygote with the disorder and an increase in a rare haplotype
      carrying DRB1*1501 and TNF-alpha(-857T) in the patients were also observed in the
      present study.

PMID- 11285132
TI  - Nomenclature for factors of the HLA system, 2000.

PMID- 11285133
TI  - The many shapes of mitochondrial membranes.
AB  - The roles of mitochondria in cell death and in aging have generated much
      excitement in recent years. At the same time, however, a quiet revolution in our
      thinking about mitochondrial ultrastructure has begun. This revolution started
      with the use of vital dyes and of green fluorescent protein fusion proteins,
      showing that mitochondria are very dynamic structures that constantly move,
      divide and fuse throughout the life of a cell. More recently, some of the first
      proteins contributing to these various processes have been discovered. Our view
      of the internal structures of mitochondria has also changed. Three-dimensional
      reconstructions obtained with high voltage electron microscopy show that cristae
      are often connected to the mitochondrial inner membrane by thin tubules. These
      new insights are brought to bear on the wealth of data collected by conventional
      electron microscopic analysis.

PMID- 11285134
TI  - Multiple pathways used for the targeting of thylakoid proteins in chloroplasts.
AB  - The assembly of the chloroplast thylakoid membrane requires the import of
      numerous proteins from the cytosol and their targeting into or across the
      thylakoid membrane. It is now clear that multiple pathways are involved in the
      thylakoid-targeting stages, depending on the type of protein substrate. Two very
      different pathways are used by thylakoid lumen proteins; one is the Sec pathway
      which has been well-characterised in bacteria, and which involves the threading
      of the substrate through a narrow channel. In contrast, the more recently
      characterised twin-arginine translocation (Tat) system is able to translocate
      fully folded proteins across this membrane. Recent advances on bacterial Tat
      systems shed further light on the structure and function of this system. Membrane
      proteins, on the other hand, use two further pathways. One is the signal
      recognition particle-dependent pathway, involving a complex interplay between
      many different factors, whereas other proteins insert without the assistance of
      any known apparatus. This article reviews advances in the study of these pathways
      and considers the rationale behind the surprising complexity.

PMID- 11285135
TI  - PTS2 protein import into mammalian peroxisomes.
AB  - Peroxisome targeting signal (PTS)2 directs proteins from their site of synthesis
      in the cytosol to the lumen of the peroxisome. Unlike PTS1 which is present in
      the great majority of peroxisomal matrix proteins and whose import mechanics have
      been dissected in considerable detail, PTS2 is a relatively rare topogenic signal
      whose import mechanisms are far less well understood. However, as is the case for
      PTS1 proteins, an inability to import PTS2 proteins leads to human disease. In
      this report, we describe the biochemical characterization of mammalian PTS2
      protein import using a semi-permeabilized cell system. We show that a PTS2
      containing reporter molecule is taken up by peroxisomes in a reaction that is
      time-, temperature-, ATP-, and cytosol-dependent. Furthermore, the import process
      is specific, saturable, and requires action of the chaperone Hsc70, the
      cochaperone Hsp40, and the peroxins Pex5p and Pex14p. We also demonstrate
      peroxisomal translocation of PTS2 reporter/antibody complexes confirming the
      import competence of higher order structures. Importantly, cultured fibroblasts
      from patients with the rhizomelic form of chondrodysplasia punctata (RCDP) which
      are deficient for the PTS2 receptor protein, Pex7p, are unable to import the PTS2
      reporter in this assay. The ability to monitor PTS2 import in vitro will permit,
      for the first time, a detailed comparison of the biochemical properties of PTS1
      and PTS2 protein import.

PMID- 11285136
TI  - Control of nuclear export of hnRNP A1.
AB  - mRNA export is mediated by RNA-binding proteins which shuttle between the nucleus
      and cytoplasm. Using an in vitro unidirectional export assay, we observe that the
      shuttling mRNA-binding protein, hnRNP A1, is exported only extremely slowly
      unless incubations are supplemented with snRNA-specific oligonucleotides which
      inhibit splicing. In vivo microinjection experiments support this conclusion.
      Like many examples of nucleocytoplasmic transport, export of hnRNP A1 requires
      energy and is sensitive to the presence of wheat germ agglutinin. It does not,
      however, require supplementation with cytoplasmic proteins. Although the
      exportin, Crm1, is needed for export of several varieties of RNA, both the in
      vitro assay and in vivo assays show that it is not required for export of hnRNP
      A1. In vitro and in vivo studies also show that inhibition of transcription
      allows continued shuttling of hnRNP A1 and in fact accelerates its export.
      Judging from the stimulatory effects of targeted destruction of snRNAs, this is
      likely to reflect completion of the covalent maturation of the RNAs with which
      hnRNP A1 associates. These observations therefore provide a simple explanation of
      why multiple RNA-binding proteins relocate to the cytoplasm upon inhibition of
      transcription in vivo.

PMID- 11285137
TI  - Rab1 interaction with a GM130 effector complex regulates COPII vesicle cis--Golgi
      tethering.
AB  - Members of the Rab family of small molecular weight GTPases regulate the fusion
      of transport intermediates to target membranes along the biosynthetic and
      endocytic pathways. We recently demonstrated that Rab1 recruitment of the
      tethering factor p115 into a cis-SNARE complex programs coat protein II vesicles
      budding from the endoplasmic reticulum (donor compartment) for fusion with the
      Golgi apparatus (acceptor compartment) (Allan BB, Moyer BD, Balch WE. Science
      2000; 289: 444-448). However, the molecular mechanism(s) of Rab regulation of
      Golgi acceptor compartment function in endoplasmic reticulum to Golgi transport
      are unknown. Here, we demonstrate that the cis-Golgi tethering protein GM130,
      complexed with GRASP65 and other proteins, forms a novel Rab1 effector complex
      that interacts with activated Rab1-GTP in a p115-independent manner and is
      required for coat protein II vesicle targeting/fusion with the cis-Golgi. We
      propose a 'homing hypothesis' in which the same Rab interacts with distinct
      tethering factors at donor and acceptor membranes to program heterotypic membrane
      fusion events between transport intermediates and their target compartments.

PMID- 11285138
TI  - Vesicular and nonvesicular transport of phosphatidylcholine in polarized HepG2
      cells.
AB  - We have investigated the transport and canalicular enrichment of fluorescent
      phosphatidylcholine (PC) in HepG2 cells using the fluorescent analogs of PC C6
      NBD-PC and beta-BODIPY-PC. Fluorescent PC was efficiently transported to the
      biliary canaliculus (BC) and became enriched on the lumenal side of the
      canalicular membrane as shown for C6-NBD-PC. Some fluorescent PC was transported
      in vesicles to a subapical compartment (SAC) or apical recycling compartment
      (ARC) in polarized HepG2 cells as shown by colocalization with fluorescent
      sphingomyelin (C6-NBD-SM) and fluorescent transferrin, respectively. Extensive
      trafficking of vesicles containing fluorescent PC between the basolateral domain,
      the SAC/ARC and the BC as well as endocytosis of PC analogs from the canalicular
      membrane were found. Evidence for nonvesicular transport included enrichment of
      the PC-analog beta-BODIPY-PC in the BC (t1/2 = 3.54 min) prior to its
      accumulation in the SAC/ARC (t1/2 = 18.5 min) at 37 degrees C. Transport of
      fluorescent PC to the canalicular membrane also continued after disruption of the
      actin or microtubule cytoskeleton and at 2 degrees C. These results indicate
      that: (i) a nonvesicular transport pathway significantly contributes to the
      canalicular enrichment of PC in hepatocytic cells, and (ii) vesicular transport
      of fluorescent PC occurs from both membrane domains via the SAC/ARC.

PMID- 11285140
TI  - Increased mitochondrial complex I activity in platelets of schizophrenic
      patients.
AB  - It is believed that dopamine and alterations of energy metabolism in cortical and
      subcortical structures are involved in the pathophysiology of schizophrenia.
      Recently, we and others have shown that dopamine may affect energy metabolism by
      interacting with mitochondrial complex I activity in rats both in vivo and in
      vitro. In this study activity of complexes I and IV was assessed in mitochondria
      isolated from blood platelet of schizophrenic patients and compared to patients
      with affective disorders and healthy control subjects. Seventy-seven in-patients
      who met DSM-IV criteria for schizophrenia (in acute exacerbation), bipolar
      disorder depressed type (BP), or recurrent major depressive disorder (MDD) and 24
      control subjects participated in the study. A highly significant increase (240%,
      p < 0.001) in complex I activity but not in complex IV, was detected in medicated
      and unmedicated schizophrenic patients compared to controls. No such change was
      observed in patients with affective disorders. The data demonstrate a specific
      and selective, alteration in platelet complex I activity in schizophrenic
      patients, which is not related to medication. If this abnormality in platelet
      mitochondria reflects brain alterations, it may further support the relevance of
      alterations in energy metabolism to the pathophysiology of schizophrenia. Finally
      in the lack of any clinically relevant biological marker for schizophrenia,
      complex I activity in platelets might become a useful peripheral marker for this
      disorder.

PMID- 11285141
TI  - Hypothalamic aggression area under serotonergic control in mouse-killing
      behaviour of rats.
AB  - The serotonergic system participates in the modulation of aggressive behaviour.
      We examined the neuronal substrate underlying serotonergic control of aggressive
      behaviour in rats using a transplantation technique. Fetal serotonergic neurons
      transplanted into the hypothalamus restored inhibition of mouse-killing behaviour
      (muricide), in rats with raphe lesions induced by a serotonergic neurotoxin, 5,7
      dihydroxytryptamine. Immunohistochemical and neurochemical studies indicated that
      the recovery of serotonergic innervation in the lateral hypothalamic area by the
      raphe grafts brought about the inhibition of muricide. The extension of
      serotonergic fibres into the lateral hypothalamic area from the grafted
      serotonergic neurons is strongly related to inhibition of muricide. These results
      indicate the possibility that serotonergic neurons regulate muricide through the
      inhibition of the activity of the lateral hypothalamic area neurons.

PMID- 11285139
TI  - Coordinate regulation of RARgamma2, TBP, and TAFII135 by targeted proteolysis
      during retinoic acid-induced differentiation of F9 embryonal carcinoma cells.
AB  - BACKGROUND: Treatment of mouse F9 embryonal carcinoma cells with all-trans
      retinoic acid (T-RA) induces differentiation into primitive endodermal type
      cells. Differentiation requires the action of the receptors for all trans, and
      9cis-retinoic acid (RAR and RXR, respectively) and is accompanied by growth
      inhibition, changes in cell morphology, increased apoptosis, proteolytic
      degradation of the RARgamma2 receptor, and induction of target genes. RESULTS: We
      show that the RNA polymerase II transcription factor TFIID subunits TBP and
      TAFII135 are selectively depleted in extracts from differentiated F9 cells. In
      contrast, TBP and TAFII135 are readily detected in extracts from differentiated
      F9 cells treated with proteasome inhibitors showing that their disappearance is
      due to targeted proteolysis. This regulatory pathway is not limited to F9 cells
      as it is also seen when C2C12 myoblasts differentiate into myotubes. Targeting of
      TBP and TAFII135 for proteolysis in F9 cells takes place coordinately with that
      previously reported for the RARgamma2 receptor and is delayed or does not take
      place in RAR mutant F9 cells where differentiation is known to be impaired or
      abolished. Moreover, ectopic expression of TAFII135 delays proteolysis of the
      RARgamma2 receptor and impairs primitive endoderm differentiation at an early
      stage as evidenced by cell morphology, induction of marker genes and apoptotic
      response. In addition, enhanced TAFII135 expression induces a novel
      differentiation pathway characterised by the appearance of cells with an atypical
      elongated morphology which are cAMP resistant. CONCLUSIONS: These observations
      indicate that appropriately timed proteolysis of TBP and TAFII135 is required for
      normal F9 cell differentiation. Hence, in addition to transactivators, targeted
      proteolysis of basal transcription factors also plays an important role in gene
      regulation in response to physiological stimuli.

PMID- 11285142
TI  - Antinociceptive effects induced by desipramine and fluoxetine are dissociated
      from their antidepressant or anxiolytic action in mice.
AB  - This study aimed to evaluate the relationship between some aspects of
      experimental depression, anxiety and the antinociceptive effects of fluoxetine
      and desipramine in mice. Acute administration of fluoxetine and desipramine (5,
      10 and 20 mg/kg, i.p.) showed significant antinociceptive effects in the hot
      plate test and against the early and late phase of the mouse formalin test,
      dissociated from its antidepressant and anxiolytic effects as measured in the
      forced swimming and in the plus-maze tests, respectively. Neither fluoxetine nor
      desipramine, at the doses tested, produced significant effects on locomotor
      activity. Furthermore, both compounds were ineffective in the tail-flick phasic
      model of nociception. In conclusion, the results suggest that without the
      distinction of serotonergic and noradrenergic contributions, the acute
      antinociceptive effects of fluoxetine and desipramine in mice are independent of
      their sedative, antidepressant and anti-anxiety properties.

PMID- 11285143
TI  - Dopaminergic sensitization of rats with and without early prefrontal lesions:
      implications for the pathogenesis of schizophrenia.
AB  - To study whether an early lesion of prefrontal cortex (PFC) would influence
      mesolimbic dopaminergic sensitization induced by intermittent electrical
      stimulation (IES) of the ventral tegmental area (VTA) or change social
      interactions in animals exposed to both electrical sensitization and prefrontal
      lesions, we examined the behaviour of rats with or without early prefrontal
      lesions following repeated electrical stimulation of the VTA. Additionally, we
      wanted to study the influence of immobilization stress on rats exposed to a
      combination of prefrontal lesion and daily restraint in Plexiglas tubes prior to
      IES. Neither early lesion of PFC nor repeated restraint influenced development of
      sensitization. However, the combination of early prefrontal lesion and IES
      resulted in changes in social interactions neither seen following IES nor in
      lesioned rats. The changes were most pronounced in the group exposed to both IES,
      prefrontal lesions and restraint. Furthermore, repeated restraint caused a
      significant increase in the threshold current for provocation of the behavioural
      response related to VTA stimulation (head stereotypies/sniffing). The
      implications of the findings for sensitization of the mesolimbic dopaminergic
      system as a model for development of schizophrenia are discussed.

PMID- 11285144
TI  - Clozapine-induced potentiation of latent inhibition is due to its action in the
      conditioning stage: implications for the mechanism of action of antipsychotic
      drugs.
AB  - Latent inhibition (LI) refers to retarded conditioning to a stimulus as a
      consequence of its non-reinforced pre- exposure. LI is impaired in some subsets
      of schizophrenic patients and in rats treated with amphetamine. Antipsychotic
      drugs (APDs) potentiate LI under conditions that are insufficient to produce LI
      in control animals, namely, low number of pre-exposures or high number of
      conditioning trials. The present experiments tested the proposition that LI
      potentiation under both conditions stems from the action of APDs in the
      conditioning stage. Experiments 1-3 used 10 pre-exposures and 2 conditioning
      trials, and tested the effects of 2.5, 5, and 10 mg/kg clozapine, respectively.
      Experiments 4-6 used 40 pre-exposures and 5 conditioning trials, with clozapine
      doses as above. Clozapine was administered in either the pre-exposure, the
      conditioning stage, or in both. In all the experiments, vehicle controls did not
      show LI. Overall, clozapine administration in conditioning, irrespective of drug
      condition in pre-exposure, produced LI. The implications of these results for the
      mechanism of action of antipsychotic drugs are discussed.

PMID- 11285145
TI  - A functional polymorphism in the promoter of monoamine oxidase A gene and bipolar
      affective disorder.
AB  - The genes encoding for the enzymes monoamine oxidase (MAO) A and B are good
      candidates to investigate bipolar affective disorder. A 30 bp repeat in the MAOA
      promoter was recently demonstrated to be polymorphic and to affect
      transcriptional activity. In a family-based association design we found that none
      of the different repeat copies was preferentially transmitted from mothers (n =
      131) to their children affected with bipolar disorder (chi(2) = 2.75, 4 d.f., p =
      0.6). Following on our previous finding of an excess of low-activity genotypes of
      catechol-O-methyltransferase in patients with a rapid cycling form of illness, we
      examined for a similar trend with MAOA alleles. In an extended sample we found a
      non-significant trend for patients with an ultra-rapid cycling form of illness (n
      = 29) to have a higher frequency of low-activity alleles compared with 92 bipolar
      patients with a non-rapid cycling course of illness (chi(2) = 2.37, 1 d.f., p =
      0.13).

PMID- 11285146
TI  - Effects of risperidone on auditory event-related potentials in schizophrenia.
AB  - Schizophrenia is associated with cognitive deficits for which treatments remain
      elusive. The effects of risperidone (an antipsychotic differing in some of its
      pharmacological properties from typical agents) on cognitive deficits have not
      been extensively investigated. Mismatch negativity (MMN), N2 and P3 are cognitive
      event-related potentials that index preattentive (MMN) and attention-dependent
      information processing (N2, P3) and provide a measure of cognitive deficits in
      schizophrenia. The effects of risperidone treatment on MMN, N2 and P3 generation
      in chronic schizophrenic patients were investigated in an open- label,
      uncontrolled study. Risperidone treatment significantly reduced psychotic
      symptoms. It was associated with a decrease of peak latencies, particularly
      pronounced for P3. However, it did not significantly affect abnormal MMNor P3
      amplitudes. The results suggest an effect of risperidone on processing speed,
      particularly in attention-dependent tasks. These results are in agreement with
      findings in recent studies on the cognitive effects of risperidone.

PMID- 11285147
TI  - New views of biogenic amine transporter function: implications for
      neuropsychopharmacology.
AB  - Biogenic amine transporters, namely the dopamine (DA), norepinephrine (NE) and 5
      hydroxytryptamine (serotonin, 5-HT) transporters (DAT, NET and 5-HTT,
      respectively) appear to be the key elements in regulating biogenic amine
      neurotransmission. These proteins therefore represent a primary target for
      therapeutic intervention in the treatment of numerous psychiatric disorders, such
      as depression, anxiety and perhaps even schizophrenia as well as drug abuse. The
      cloning of DAT, NET and 5-HTT and development of selective radioligands for them
      over the last decade has dramatically increased our understanding of their
      location, structure and function. These breakthroughs have also enabled
      remarkable progress in determining how biogenic amine transporters are regulated
      under not only normal conditions but also when confronted with acute or chronic
      exposure to a variety of stimuli including psychotherapeutic drugs. Because of
      the important therapeutic consequences of a better understanding of these
      transporters, the present review discusses recent advances in defining their
      mechanism of action, location and regulation and the implications of the newer
      data for neuropsychopharmacology.

PMID- 11285148
TI  - Treatment of schizophrenia in low-income countries.
AB  - The introduction of the novel antipsychotics has had a major impact upon the
      treatment of schizophrenia. However, the greater acquisition costs of these drugs
      puts them beyond the reach of large sectors of the world's population.
      Consequently, the gap between the levels of care in high-income and low-income
      countries is likely to widen even further. Co-ordinated global action is
      necessary to ensure greater accessibility of these drugs. Cost-effectiveness
      studies in low-income countries need to be undertaken. The considerable evidence
      for improved safety and efficacy of low-dose compared to high-dose classical
      antipsychotics offers an alternative that could be implemented immediately in low
      income countries.

PMID- 11285149
TI  - Knockout Corner: 5-HT(1A) receptor inactivation: anxiety or depression as a
      murine experience.
AB  - 5-HT(1A) receptors play a critical role in the pathophysiology of anxiety and
      depression as well as in the mode of action of anxiolytic and antidepressant
      drugs. Mice with a targeted inactivation of the 5HT(1A) receptor show a phenotype
      that is associated with a gender-modulated and gene/dose-dependent increase of
      anxiety-related and antidepressant-like behaviours. Since this behavioural
      phenotype was observed in animals in which the mutation was bred into mice of
      different genetic backgrounds, 5-HT(1A) receptor knockout mice represent a useful
      model system for advanced investigations of 5-HT(1A) genotype/phenotype
      interaction.

PMID- 11285150
TI  - Three cases of improvement of tardive dyskinesia following olanzapine treatment.
AB  - To date, clozapine is the only antipsychotic agent that has established itself as
      having minimal, if any, risk of tardive dyskinesia (TDk). In patients with TDk,
      clozapine permits the dyskinesia to disappear in approx. 50% of cases,
      particularly those with dystonic features, i.e. tardive dystonia (TDt) (Gardos,
      1999). Unfortunately, clozapine is not always efficacious. Furthermore, some
      patients cannot be treated with clozapine because of its side-effects. Olanzapine
      is a serotonin-dopamine-receptor antagonist, which has an affinity for
      neuroreceptors similar to that of clozapine. Pooled tolerability data from
      controlled trials show that the overall incidence of TDk in patients treated with
      olanzapine is significantly lower than in patients treated with haloperidol
      (Tollefson et al., 1997). Here, we report three cases of patients affected by
      tardive disorders who dramatically improved after olanzapine treatment.

PMID- 11285151
TI  - Decline in rate of mother-to-child transmission of HIV-1 over time in Africa:
      possible role of stage of the epidemic.

PMID- 11285152
TI  - Successful shortening from seven to four days of parenteral beta-lactam treatment
      for common childhood infections: a prospective and randomized study.
AB  - OBJECTIVES: To explore whether 4-day parenteral beta-lactam therapy is as
      effective as 7-day therapy for children hospitalized for parenteral
      antimicrobials. METHODS: A series of patients aged 3 months to 15 years who
      fulfilled strict criteria for bacterial pneumonia, other respiratory infections,
      sepsis-like infections, and other acute infections were prospectively randomized
      to receive parenteral penicillin or cefuroxime randomly for 4 or 7 days. Besides
      blood and throat cultures, the etiology was searched by serology for 23 different
      agents. RESULTS: Of 154 children analyzed, a probable etiology was established in
      96. Of those, a bacterial infection, with or without concomitant viral infection,
      was disclosed in 80% and 94% in the 4-day and 7-day treatment groups,
      respectively; pneumococcus being the commonest agent. There was one possible
      treatment failure in the 4-day group, but with a questionable relation to the
      short course. Three patients in the 4-day and two in the 7-day group underwent
      treatment changes, or were rehospitalized within 30 days. All children recovered
      entirely. CONCLUSIONS: Shortening parenteral beta-lactam treatment to 4 days in
      infections for which most parenteral antimicrobials are instituted, is not only
      safe, but reduces costs, is ecologically sound, and minimizes the risks of
      nosocomial infections and other adverse effects of treatment.

PMID- 11285153
TI  - Effect of surfactant and specific antibody on bacterial proliferation and lung
      function in experimental pneumococcal pneumonia.
AB  - OBJECTIVE: To investigate the effect of surfactant and specific antibody on
      bacterial proliferation in experimental pneumococcal pneumonia. METHODS: Near
      term newborn rabbits received a standard dose (10(7)) of type 3 pneumococci via
      the airways. Control animals were sacrificed 1 minute later. Other animals were
      ventilated for 5 hours and treated via the tracheal cannula with surfactant
      (Curosurf 200 mg/kg), a mixture of surfactant and a polyclonal antipneumococcal
      antibody, the antibody without surfactant, or saline. RESULTS: There was a
      significant bacterial proliferation in lung tissue in all animals ventilated for
      5 hours. Bacterial growth, expressed as log10 colony forming units (CFU) per gram
      of lung tissue was less prominent in animals treated with a mixture of surfactant
      and specific antibody than in animals treated with antibody alone (median, 7.51,
      range, 6.80--7.70 vs. median, 7.92, range, 7.07--8.50; P < 0.05). Dynamic lung
      thorax compliance was improved with surfactant or surfactant plus antibody in
      comparison with saline or antibody alone. CONCLUSIONS: The data suggest that the
      suppressive effect of the antibody on bacterial proliferation becomes evident
      only when surfactant is administered together with the antibody.

PMID- 11285154
TI  - Tropical diabetic hand syndrome: risk factors in an adult diabetes population.
AB  - OBJECTIVES: To determine risk factors for the tropical diabetic hand syndrome, a
      condition associated with significant morbidity and mortality in Africa. METHODS:
      This was a case-control study of a Tanzanian diabetes population presenting with
      the syndrome during February 1998 to March 2000. A case patient was defined as
      any patient with diabetes presenting with hand cellulitis, ulceration, or
      gangrene. Control patients were randomly selected patients with diabetes who had
      no hand symptoms. RESULTS: Thirty-one case patients and 96 control patients were
      identified. The median age of case patients was 52 years (range, 28--76 y); 58%
      were male; 4 patients (16%) died. Precipitating events included papule (n = 6),
      insect bites (n = 6), boils (n = 5), burns (n = 2), or trauma (n = 3). Case and
      control patients were similar for presence of micro- and macrovascular disease
      and occupation. On logistic regression analysis, independent risk factors were
      body mass index of 20 or less (odds ratio [OR] = 18.0; 95% confidence interval
      [CI] = 4.3--97.0; P < 0.001), peripheral neuropathy (OR = 23.0; 95% CI = 5.3-
      124.0; P < 0.001), or type I diabetes, (OR = 6.7; 95% CI = 2.0--24.0, P < 0.01).
      CONCLUSION: The major risk factors for the tropical diabetic hand syndrome are
      intrinsically related to the underlying disease. Thus, prevention of hand
      infections may require aggressive glucose control, and education on hand care and
      the importance of seeing a doctor promptly at the onset of symptoms.

PMID- 11285155
TI  - Patients' perceptions of blood transfusion risks in Karachi, Pakistan.
AB  - OBJECTIVE: To evaluate the understanding of and attitudes toward risks of blood
      transfusions among transfusion recipients in Karachi. METHODS: One hundred forty
      one transfusion recipients from 13 major Karachi hospitals were interviewed.
      Indications for transfusion were obtained by reviewing the patients' medical
      records. RESULTS: The most common indications for transfusion were surgical
      complications (n = 77, 55%), anemia (n = 34, 24%), and generalized weakness (n =
      15, 11%). Most recipients (n = 103, 80%) had never heard of viral hepatitis, and
      44 (31%) had never heard of acquired immunodeficiency syndrome (AIDS). Ninety
      four recipients (66%) believed that generalized weakness was a valid indication
      for blood transfusion. Sixty-nine recipients (49%) were not willing to pay an
      increased price for blood that was screened for blood-borne pathogens.
      CONCLUSIONS: Blood recipients in Karachi are unaware of the risks of
      transfusions, and the reasons given by the ordering physician for many of the
      transfusions were not consistent with international guidelines. Steps to educate
      the public about the risks of transfusions and practitioners about the
      indications for transfusion could prevent blood-borne virus transmission in
      Karachi.

PMID- 11285156
TI  - Tattoos as risk factors for transfusion-transmitted diseases.
AB  - BACKGROUND: Several infectious diseases have been found to be associated with
      tattooing, including some transfusion-transmitted diseases (TTDs). Information on
      tattooing has been included in screening interviews of prospective blood donors
      and may be a reason for deferral. METHODS: Review of articles identified through
      Medline (and other computerized data bases) using medical subject heading (MeSH)
      terms and textwords for "tattooing," "transfusion", "hepatitis", "human
      immunodeficiency virus", "acquired immunodeficiency syndrome", "syphilis",
      "Chagas disease", "infection", "risk factors", and their combinations. RESULTS:
      There is strong evidence for the transmission of hepatitis B virus (HBV)
      infection, hepatitis C virus (HCV) infection, and syphilis by tattooing.
      Tattooing may also transmit the human immunodeficiency virus (HIV), although
      convincing evidence is still lacking. There is little or no evidence that other
      TTDs can be transmitted by tattooing. Epidemiologic studies to date have shown a
      large variation in odds ratio estimates of the association between tattooing and
      HBV, HCV, and HIV infections. CONCLUSION: Further studies are required to clarify
      the risk of tattoos in transmitting infectious diseases through blood
      transfusions. A reassessment of tattoos as a screening criterion among blood
      donors is justified.

PMID- 11285157
TI  - Study of biologic attributes of Cuban dengue 2 virus after serial passage in
      primary dog kidney cells.
AB  - OBJECTIVE: The serial passage of dengue viruses in primary dog kidney (PDK) cells
      has resulted in selection of attenuated viruses. However, the molecular changes
      responsible for loss of virulence are not well characterized. This article
      describes the isolation and biologic attributes of one dengue 2 virulent strain
      as a first step to allow the study of determinants of virulence at the molecular
      level. METHODS: A15 dengue 2 Cuban strain was isolated from the viremic plasma of
      a patient with uncomplicated dengue fever during the 1981 epidemic. This was then
      subjected to serial passage in PDK cells. Viruses resulting from several PDK
      passages were compared to the parent strain for plaque size and temperature
      sensitivity, neurovirulence in newborn mice, and cytopathogenic effects on LLC
      MK(2) and C6/36-HT cell lines. RESULTS: A15 dengue 2 Cuban strain was
      successfully propagated in PDK cells. Primary dog kidney 52 to 53 viruses
      exhibited several biologic attributes, such as small plaques, temperature
      sensitivity, reduced mouse neurovirulence, and cytopathic effect in permissive
      cell lines. CONCLUSIONS: These results represent the first step to allow
      attenuation of this strain of dengue 2 virus.

PMID- 11285158
TI  - Initial isolation of Candida dubliniensis from the Middle East.
AB  - Two isolates of Candida dubliniensis were identified from a collection of 30
      examined from Israel in a molecular epidemiology study. The 30 isolates were
      tentatively identified as Candida albicans. The new species, C. dubliniensis, is
      being reported from new geographic locales. These two isolates, from an Arab and
      a Druze patient, are the first to be reported from the Middle East.

PMID- 11285159
TI  - Systematic review of combination antiretroviral therapy with didanosine plus
      hydroxyurea: a partial solution to Africa's HIV/AIDS problem?
AB  - Effective antiretroviral therapy remains beyond the reach of most human
      immunodeficiency virus (HIV)-infected persons living in the third world because
      of its tremendous cost. The cancer drug, hydroxyurea, inhibits HIV-1 replication
      in vitro and, when combined with didanosine (ddI), results in significant
      antiretroviral synergy. In vivo, hydroxyurea specifically targets quiescent
      lymphocytes and macrophages, important cellular reservoirs for HIV-1, and the
      combination of ddI plus hydroxyurea effectively reduces plasma HIV-1 RNA levels.
      Combination ddI-hydroxyurea costs about one-eighth as much as currently
      recommended triple drug combinations, and several countries in Africa are
      exploring the feasibility of widescale use of ddI-hydroxyurea for their HIV
      infected populations. Intrigued by its potential relevance for Africa, the
      authors reviewed the literature on the in vitro and clinical efficacy of ddI plus
      hydroxyurea against HIV. The combination of ddI plus hydroxyurea is an effective
      and potentially more affordable regimen for HIV-infected persons living in poorer
      countries.

PMID- 11285160
TI  - Hansen's disease in a native-born, United States resident, after a brief stay in
      an endemic area abroad.

PMID- 11285161
TI  - Unusual presentation of amebic liver abscess with thrombocytopenia and
      splenomegaly.

PMID- 11285162
TI  - International work: something for everyone.

PMID- 11285163
TI  - Clinical features and epidemiology of tick typhus in travelers.
AB  - BACKGROUND: Epidemiologic features of tick typhus among German travelers has not
      been surveyed recently. METHODS: Clinical features, travel and medical histories
      in 78 patients with tick typhus who presented to a German outpatient clinic for
      Infectious and Tropical Diseases were investigated, in order to identify common
      epidemiological factors and potential strategies of prevention. Diagnosis was
      confirmed by serological detection of IgG- and IgM-antibodies to Rickettsia
      conorii by indirect immunofluorescence. RESULTS: The majority of patients (71.8%)
      had visited southern Africa prior to presentation. All patients presented with
      fever as the main symptom. An eschar was still present in 68 patients (87.2%)
      with regional lymphadenitis in 19.2%. However, only a minority of patients
      (17.9%) remembered a tick bite at the location of the eschar. CONCLUSION: Efforts
      to reduce the incidence of tick typhus in travelers should focus on preventive
      measures targeting behavioral changes. Avoiding tick bites during travel to
      endemic areas appears to be the single most important prophylactic action. Taking
      this into consideration, it should be possible to decrease the number of
      travelers returning with tick typhus significantly by adequate pretravel
      counseling.

PMID- 11285164
TI  - Health professionals' attitudes toward acute diarrhea management.
AB  - BACKGROUND: Travelers' diarrhea is the most frequent health problem in those
      participating in international journeys, and is responsible for many
      consultations abroad and on return home. METHODS: A questionnaire assessing
      attitudes toward treatment and management of travel-related and nontravel-related
      diarrhea was administered to 542 GPs, nurses and pharmacists. RESULTS: Health
      professionals' attitudes to management of acute diarrhea are variable, with
      marked divergence regarding adherence to published "good practice" guidelines and
      recommendations. Inconsistencies exist in stated attitudes toward prescribing
      antispasmodics and antimotility agents and actual prescribing behavior.
      CONCLUSIONS: Current treatment guidelines may be outdated. Inappropriate or
      delayed treatment disadvantages the patient. Limiting the use of antidiarrheal
      agents can deny access, for those inflicted with diarrhea, to a medication which
      may shorten symptomatology and morbidity, and speed the return to normality.
      Review of guidelines for diarrhea management in adults is overdue, as is
      standardization of treatment response. Educational initiatives are required to
      encourage active intervention and improved provision of care.

PMID- 11285165
TI  - Predictors of pretravel consultation in tourists from Quebec (Canada).
AB  - BACKGROUND: Although many tourists from Quebec (Canada) each year visit
      destinations at risk for infectious diseases, only a few of them seek travel
      health advice. To identify the determinants of travel health consultation, we
      conducted a study among Quebec's tourists visiting two popular sun destinations.
      METHODS: A conceptual model based on psychosocial determinants of human behavior
      was constructed. A cross-sectional survey was carried out, from January to April
      1999, on two samples of travelers planning to visit Mexico and the Dominican
      Republic. One sample was composed of people who did not consult a travel clinic
      (cluster sampling in seven flights), and the other sample was one of clients of
      travel clinics (purposive selection of 13 specialized clinics located in Quebec).
      A 34-item self-administered bilingual questionnaire was distributed to travelers.
      Statistical analysis included a multivariate approach (logistic regression).
      RESULTS: A total of 2,242 travelers were surveyed (response rate in flight 75%
      and in clinics 99%). We present only results reported by French-speaking
      tourists: 1,152 who did not consult a travel clinic and were reached in flight,
      and 449 who were reached in clinics. Multivariate analyses indicated that travel
      agent recommendation was the most important predictor of consultation among
      travelers (OR 8.0, 95% CI 5.1-13), especially among those under 45 years of age
      and those who never sought pretravel consultation before (OR 21, 95% CI 11-41).
      Other important predictors were: traveling for the first time, traveling with
      children, previous consultation, perception about efficacy of immunization, risk
      perception, and information from travel agent, family doctor, and pharmacist.
      CONCLUSIONS: Despite its limitations, this study provides data that should help
      improve public health interventions aimed at encouraging travelers to get a
      pretravel consultation.

PMID- 11285166
TI  - Imported malaria treated in Melbourne, Australia: epidemiology and clinical
      features in 246 patients.
AB  - BACKGROUND: Imported malaria is increasing in nonendemic countries, including
      Australia. The objective of this study was to describe the epidemiology and
      clinical features of travelers with imported malaria presenting to a specialist
      infectious diseases hospital. METHODS: A retrospective case series of 246
      consecutively admitted inpatients with laboratory confirmed malaria. The main
      outcome measures were the proportion of patients infected with each malaria
      species, and relationship between species and country of birth, area of
      acquisition, adequacy of chemoprophylaxis, clinical features, laboratory
      investigations, and treatment. RESULTS: Plasmodium vivax caused 182 (68.9%)
      episodes, Plasmodium falciparum caused 71 (26.9%), Plasmodium ovale caused 5
      (1.9%), and Plasmodium malariae 1 (0.4%). Fifty-six percent of patients reported
      chemoprophylaxis use. People born in a country with endemic malaria (36.6%) were
      less likely to have used chemoprophylaxis. Malaria was most commonly acquired in
      Papua New Guinea and Southeast Asia. The median times to diagnosis after return
      to Australia for P. falciparum and P. vivax infections were 1 and 9 weeks
      respectively. The longest interval between last arrival in Australia and
      presentation with P. falciparum malaria was 32 weeks. Fever (96%), headache
      (74%), and a tender or palpable spleen (40%), were the most common clinical
      features. Diarrhea was more common in P. falciparum, and rigors in P. vivax
      infections. Thrombocytopenia (71%), abnormal liver function tests and an elevated
      C-reactive protein (85%) were common. Six patients had severe falciparum malaria
      but no deaths occurred during the study period. CONCLUSION: Malaria remains a
      health threat for those traveling in endemic areas and is associated with failure
      to use chemoprophylaxis appropriately. Nonspecific clinical features may lead to
      delayed diagnosis and misdiagnosis. Malaria should be suspected in the febrile
      traveler, regardless of birthplace, prophylaxis, symptomatology, or the time that
      has elapsed since leaving the malarious area.

PMID- 11285167
TI  - Cholera vaccines.

PMID- 11285168
TI  - Schistosomiasis in Africa and international travel.

PMID- 11285169
TI  - Malaria in Rhode Island: observations from 1990 to 1998.

PMID- 11285170
TI  - Human myiasis: an unusual imported infestation in Calabria, Italy.

PMID- 11285171
TI  - Changing epidemiology of hepatitis A: time for vaccination in childhood.

PMID- 11285173
TI  - Polio immunization before travel to endemic countries.

PMID- 11285186
TI  - The chemistry and biology of aflatoxin B(1): from mutational spectrometry to
      carcinogenesis.
AB  - Dietary exposure to aflatoxin B(1) (AFB(1)) is associated with an increased
      incidence of hepatocellular carcinoma (HCC), especially in populations in which
      exposure to hepatitis B virus (HBV) is a common occurrence. Most HCC samples from
      people living where HBV is prevalent have one striking mutational hotspot: a GC-
      >TA transversion at the third position of codon 249 of the p53 gene. In this
      review, the chemical reaction of an electrophilic derivative of aflatoxin with
      specific DNA sequences is examined, along with the types of mutations caused by
      AFB(1) and the sequence context dependence of those mutations. An attempt is made
      to assign the source of these mutations to specific chemical forms of AFB(1)-DNA
      damage. In addition, epidemiological and experimental data are examined regarding
      the synergistic effects of AFB(1) and HBV on HCC formation and the predominance
      of one hotspot GC-->TA transversion in the p53 gene of affected individuals.

PMID- 11285187
TI  - Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis
      in F344 rats by JTE-522, a selective COX-2 inhibitor.
AB  - Recent studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2)
      and elevation of COX-2-mediated synthesis of prostaglandin E(2) (PGE(2)) were
      observed in various cancers including esophageal cancer, but their roles in
      carcinogenesis of the esophagi still remain unclear. To address the issue, we
      observed the reduction of N:-nitrosomethylbenzylamine (NMBA)-induced
      tumorigenesis in rat esophagi via JTE-522 (4-[4-cyclohexyl-2-methyloxazol-5-yl]-2
      fluorobenzenesulfonamide), a selective COX-2 inhibitor. In this study, 54 F344
      male rats were divided into nine groups; JTE-522 (3, 9 and 30 mg/kg) was
      administered orally. We also examined the effects of JTE-522 on COX-2 mRNA and
      synthesis of PGE(2). In the group in which JTE-522 was administered
      intermittently at a daily dose of 30 mg/kg, the number of NMBA-induced esophageal
      tumors per rat significantly reduced, to 62% (P< 0.05), but the size of the
      tumors was not significantly inhibited. In the group in which JTE-522 was
      administered continuously five times weekly for 24 weeks at a daily dose of 9
      mg/kg, both the number and size of tumors significantly reduced, to 29 and 44%,
      respectively (P<0.05). Furthermore, JTE-522 suppressed not only tumor formation
      but also developing carcinomas (P<0.0021) [corrected]. In this study, treatment
      with NMBA alone resulted in an approximately 5-fold rise in expression of COX-2
      mRNA detected by semi-quantitative RT-PCR analysis and an approximately 7-fold
      increase in the production of PGE(2) measured by ELISA compared with the normal
      esophageal mucosa. The up-regulated COX-2 expression did not decrease with the
      treatment of JTE-522 at the 3, 9 and 30 mg/kg doses; however, the increased
      levels of PGE(2) synthesis were significantly decreased by administering JTE-522
      (P<0.01). Our study suggests that COX-2-mediated PGE(2) is important in NMBA
      induced esophageal tumorigenesis in rats, and therefore may be a promising
      chemotherapeutic target for the prevention and treatment of esophageal cancer,
      especially with selective COX-2 inhibitors.

PMID- 11285188
TI  - Short-term dosing of alpha-hydroxytamoxifen results in DNA damage but does not
      lead to liver tumours in female Wistar/Han rats.
AB  - It is now generally accepted that activation of tamoxifen occurs as a result of
      metabolism to alpha-hydroxytamoxifen. In this study, alpha-hydroxytamoxifen was
      given to female Wistar/Han rats (0.103 or 0.0103 mmol/kg, intraperitoneally,
      daily for 5 days). This resulted in liver DNA damage, determined by (32)P-post
      labelling, of 3333 +/- 795 or 343 +/- 68 adducts/10(8) nucleotides, respectively
      (mean +/- SD, n = 4). Following HPLC separation, the retention times of the major
      alpha-hydroxytamoxifen DNA adducts were similar to those seen following the
      administration of tamoxifen. However, after rats were treated with alpha
      hydroxytamoxifen (0.103 mmol/kg) for 5 days and the animals kept for up to 13
      months, no liver tumours developed (0/7 rats), even with phenobarbital promotion
      (0/5 rats). GST-P foci were detected in the liver, but only after 13 months was
      their number or area significantly increased over the corresponding controls.
      When alpha-hydroxytamoxifen was given to female lambda/lacI transgenic rats
      (0.103 mmol/kg orally for 10 days) and the animals killed 46 days later, there
      was an approximate 1.8-fold increase in mutation frequency but no significant
      increase in G:C to T:A transversions as described after tamoxifen treatment. It
      is concluded that DNA damage alone, resulting from the short-term administration
      of alpha-hydroxytamoxifen, is not sufficient to initiate liver tumours even with
      phenobarbital promotion. As with tamoxifen, long-term exposure may be required to
      allow promotion and progression of transformed cells.

PMID- 11285189
TI  - Se-methylselenocysteine induces apoptosis through caspase activation in HL-60
      cells.
AB  - Apoptosis, a programmed process of cell suicide, has been proposed as the most
      plausible mechanism for the chemopreventive activities of selenocompounds. In our
      study, we found that Se-methylselenocysteine (MSC) induced apoptosis through
      caspase activation in human promyelocytic leukemia (HL-60) cells. Measurements of
      cytotoxicity, DNA fragmentation and apoptotic morphology revealed that MSC was
      more efficient at inducing apoptosis than selenite, but was less toxic. Moreover,
      MSC increased both the apoptotic cleavage of poly(ADP-ribose) polymerase (PARP)
      and caspase-3 activity, whereas selenite did not. We next examined whether
      caspases and serine proteases are required for the apoptotic induction by MSC. A
      general caspase inhibitor, z-VAD-fmk, dramatically decreased cytotoxicity in MSC
      treated HL-60 cells and several other apoptotic features, such as, caspase-3
      activation, the apoptotic DNA ladder, TUNEL-positive staining and the DNA double
      strand break. Interestingly, a general serine protease inhibitor, AAPV-cmk, also
      effectively inhibited MSC-mediated cytotoxicity and apoptosis. These results
      demonstrate that MSC is a selenocompound that efficiently induces apoptosis in
      leukemia cells and that proteolytic machinery, in particular caspase-3, is
      necessary for MSC-induced apoptosis. On the other hand, selenite-induced cell
      death could be derived from necrosis rather than apoptosis, since selenite did
      not significantly induce several apoptotic phenomena, including the activation of
      caspase-3.

PMID- 11285190
TI  - Xeroderma pigmentosum group A gene action as a protection factor against 4
      nitroquinoline 1-oxide-induced tongue carcinogenesis.
AB  - To test the hypothesis that nucleotide excision repair (NER) plays a protective
      role in chemical carcinogenesis in internal organs, xeroderma pigmentosum group A
      gene-deficient (XPA(-/-)) mice, heterozygous (XPA(+/-)) and wild-type (XPA(+/+))
      mice were orally administered 0.001% 4-nitroquinoline 1-oxide (4NQO) in their
      drinking water and compared. After 50 weeks of 4NQO exposure, tongue squamous
      cell carcinomas (SCCs) occurred in XPA(-/-) mice only, no tumors being observed
      in XPA(+/-) and XPA(+/+) animals. Of the XPA(-/-) mice 86% had tumors and 100%
      demonstrated multiple foci of dysplastic epithelium in the tongue. Accumulation
      of p53 protein was immunohistochemically detected in 56% of the SCCs. Mutational
      analysis of the p53 gene (exons 4-10) in carcinoma DNA revealed missense
      mutations in exons 5 and 9 in four of 20 samples. Our results clearly demonstrate
      that the NER gene XPA acts as a defensive factor against 4NQO-induced tongue
      carcinogenesis in vivo.

PMID- 11285191
TI  - p53 is dispensable for UV-induced cell cycle arrest at late G(1) in mammalian
      cells.
AB  - Genotoxic agents, including gamma-rays and UV light, induce transient arrest at
      different phases of the cell cycle. These arrests are required for efficient
      repair of DNA lesions, and employ several factors, including the product of the
      tumor suppressor gene p53 that plays a central role in the cellular response to
      DNA damage. p53 protein has a major function in the gamma-ray-induced cell cycle
      delay in G(1) phase. However, it remains uncertain as to whether p53 is also
      involved in the UV-mediated G(1) delay. This report provides evidence that p53 is
      not involved in UV-induced cellular growth arrest in late G(1) phase. This has
      been demonstrated in HeLa cells synchronized at the G(1)/S border by aphidicolin,
      followed by UV exposure. Interestingly, the length of this p53-independent G(1)
      arrest has been shown to be UV dose-dependent. Similar results were also obtained
      with other p53-deficient cell lines, including human promyelocytic leukemia HL-60
      and mouse p53 knock-out cells. As expected, all of these cell lines were
      defective in gamma-ray-induced cell growth arrest at late G(1). Moreover, it is
      shown that in addition to cell cycle arrest, HL-60 cells undergo apoptosis in
      G(1) phase in response to UV light but not to gamma-rays. Together, these
      findings indicate that p53- compromised cells have a differential response
      following exposure to ionizing radiation or UV light.

PMID- 11285192
TI  - DNA double-strand breaks trigger apoptosis in p53-deficient fibroblasts.
AB  - DNA double-strand breaks (DSBs) are induced by ionizing radiation (IR) and
      various radiomimetic agents directly, or indirectly as a consequence of DNA
      repair, recombination and replication of damaged DNA. They are ultimately
      involved in the generation of chromosomal aberrations and were reported to cause
      genomic instability, gene amplification and reproductive cell death. To address
      the question of whether DSBs act as a trigger of apoptosis, we induced DSBs by
      means of restriction enzyme electroporation and compared the effect with IR in
      mouse fibroblasts that differ in p53 status [wild-type (+/+) versus p53-deficient
      (-/-) cells]. We show that (i) electroporation of PVU:II is highly efficient in
      the induction of DSBs, (ii) electroporation of PVU:II increases the rate of
      apoptosis, but not of necrosis in p53-/- cells, (iii) treatment with gamma-rays
      induces both apoptosis and necrosis in p53-/- cells, (iv) the frequency of DSBs
      correlates with the yield of apoptosis and (v) both PVU:II and gamma-ray
      treatment reduce the level of anti-apoptotic Bcl-2 protein in p53-/- cells
      whereas the level of Bax remains unaltered. Cells expressing wild-type p53 were
      more resistant than p53-deficient cells as to the induction of apoptosis and did
      not show Bcl-2 decline upon treatment with PVU:II and gamma-rays. The data
      provide evidence that blunt-ended DSBs induced by restriction enzyme PVU:II act
      as a highly efficient trigger of apoptosis, but not of necrosis. This process is
      related to Bcl-2 decline and does not require p53.

PMID- 11285193
TI  - Preventive effects of Juzen-taiho-to on N-methyl-N-nitrosourea and estradiol
      17beta-induced endometrial carcinogenesis in mice.
AB  - Two experiments were conducted to determine effects of Juzen-taiho-to on
      endometrial carcinogenesis in mice. In the first experiment, Juzen-taiho-to
      treatment (2 weeks) decreased the levels of estradiol-17beta (E(2))-stimulated
      expression of c-fos/jun mRNA and their oncoproteins, determined by reverse
      transcription-polymerase chain reaction and Southern blot analysis, and the
      immunohistochemical method, in the uteri of ovarectomized mice. For the second
      experiment, 93 female ICR mice were given N-methyl-N-nitrosourea (MNU) solution
      (1 mg/100 g body weight) and normal saline (as controls) into their left and
      right uterine corpora, respectively, and were divided into four groups. Group 1
      was given a diet containing 0.2% Juzen-taiho-to and 5 p.p.m. E(2). Group 2 was
      given a diet containing 5 p.p.m. E(2) alone. Group 3 was given a diet containing
      0.2% Juzen-taiho-to alone. Group 4 was kept on the basal diet alone and treated
      as a control. Juzen-taiho-to treatment significantly decreased incidences of the
      uterine endometrial atypical (P<0.01), complex (P<0.05) and simple hyperplasias
      (P<0.01), under estrogenic stimulation. It is suggested that Juzen-taiho-to has
      an inhibitory effect on E2-related endometrial carcinogenesis in mice, relevantly
      through suppression of estrogen-induced c-fos/jun-expression.

PMID- 11285194
TI  - Genetic polymorphisms in DNA repair genes and risk of lung cancer.
AB  - Polymorphisms in DNA repair genes may be associated with differences in the
      repair efficiency of DNA damage and may influence an individual's risk of lung
      cancer. The frequencies of several amino acid substitutions in XRCC1 (Arg194Trp,
      Arg280His and Arg399Gln), XRCC3 (Thr241Met), XPD (Ile199Met, His201Tyr, Asp312Asn
      and Lys751Gln) and XPF (Pro379Ser) genes were studied in 96 non-small-cell lung
      cancer (NSCLC) cases and in 96 healthy controls matched for age, gender and
      cigarette smoking. The XPD codon 312 Asp/Asp genotype was found to have almost
      twice the risk of lung cancer when the Asp/Asn + Asn/Asn combined genotype served
      as reference [odds ratio (OR) 1.86, 95% confidence interval (CI), 1.02-3.40]. In
      light cigarette smokers (less than the median of 34.5 pack-years), the XPD codon
      312 Asp/Asp genotype was more frequent among cases than in controls and was
      associated with an increased risk of NSCLC. Compared with the Asn/Asn carriers,
      the OR in light smokers with the Asp/Asn genotype was 1.70 (CI0.35 0.43-6.74) and
      the OR in those with the Asp/Asp genotype was 5.32 (CI0.35-21.02) (P trend =
      0.01). The 312 Asp/Asp genotype was not associated with lung cancer risk in never
      smokers or heavy smokers (>34.5 pack-years). The XPD-312Asp and -751Lys
      polymorphisms were in linkage disequilibrium in the group studied; this finding
      was further supported by pedigree analysis of four families from Utah. The XPD
      312Asp amino acid is evolutionarily conserved and is located in the seven-motif
      helicase domain of the RecQ family of DNA helicases. Our results indicate that
      these polymorphisms in the XPD gene should be investigated further for the
      possible attenuation of DNA repair and apoptotic functions and that additional
      molecular epidemiological studies are warranted to extend these findings.

PMID- 11285195
TI  - Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a
      probiotic microorganism.
AB  - Regulation of innate immunity may be an effective means of cancer control.
      Delaying cancer onset is regarded as an important mode of action in cancer
      prevention. We have been investigating the chemopreventive mechanisms of
      Lactobacillus casei Shirota (LcS), a probiotic strain. In this study, we
      evaluated the effect of LcS on tumor onset and the involvement of natural killer
      (NK) cells using a 3-methylcholanthrene-induced carcinogenesis model. C3H/HeN
      mice were divided into three groups, according to treatment: vehicle-treated,
      treated with vehicle only; control, 3-methylcholanthrene treated; LcS, 3
      methylcholanthrene and LcS treated. 3-Methylcholanthrene was injected
      intradermally at 7 weeks of age. LcS was mixed into the diet (0.05%, w/w), which
      the mice were fed from the day of 3-methylcholanthrene injection onward. Tumor
      incidence was observed weekly. Profiles of splenic NK cells, in vitro
      cytotoxicity and the proportion, in the early stage of carcinogenesis were
      analyzed at 5 weeks after the injection. The tumor suppressive effect of LcS was
      also evaluated in a beige mouse model that is genetically deficient in NK cells.
      LcS delayed tumor onset and reduced tumor incidence in the results with C3H/HeN
      mice (P< 0.05). More specifically, tumor incidence in the control group was 33%
      at 6 weeks after the injection and 83% at 11 weeks as opposed to 0 and 42%,
      respectively, in the LcS group. NK cell cytotoxicity was significantly higher
      than in the control group, and the number of NK cells also increased in the LcS
      group of C3H/HeN mice. However, LcS failed to suppress tumorigenesis in the beige
      mouse. These findings suggest that enhancement of the cytotoxicity of NK cells by
      LcS delays tumor onset.

PMID- 11285196
TI  - Dietary energy restriction inhibits ERK but not JNK or p38 activity in the
      epidermis of SENCAR mice.
AB  - Ongoing studies in our laboratory have demonstrated that dietary energy
      restriction (DER) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP
      1 transcription factor binding to DNA in the epidermis of SENCAR mice. To dissect
      the specific signal transduction pathways through which DER inhibits the AP-1:DNA
      binding, we analyzed the activities of three major MAP kinases that lead to the
      induction of AP-1. The changes in ERK1 and ERK2 protein expression and
      phosphorylation were further characterized by western blot analysis. Female
      SENCAR mice were pre-fed ad libitum (AL) or 40% DER diet for 8-10 weeks. The
      kinase activities in mouse epidermis were determined by immune complex kinase
      assays at 0.5, 1, 4, or 6 h following treatment with 3.2 nmol TPA to the shaved
      dorsal backs. ERK activity at 1 h post-TPA treatment was nearly 5-fold (P< 0.005)
      above basal levels in AL mice while the increase was abolished in DER mice. The
      TPA-induced ERK activity in AL mice was accompanied by increased phosphorylation
      of ERK1 and ERK2 (P< 0.05), which was abrogated in DER mice. In addition, DER
      mice exhibited reduced expression of total ERK1 and ERK2 and higher proportions
      of ERK1 and ERK2 phosphorylation in comparison with AL mice (P<0.05). JNK
      activity was decreased at 1 and 6 h but increased at 4 h (P<0.05) post-TPA
      treatment. TPA did not change p38 kinase activity at the time points tested.
      Neither JNK nor p38 activity was altered by DER. Taken together, our results
      indicated for the first time that DER blocked the TPA stimulation of ERK activity
      and suggested that the inhibition of TPA-induced AP-1 activity by DER is likely
      through inhibition of ERK but not JNK or p38 kinase pathway.

PMID- 11285197
TI  - Promoting effects of xylazine on development of thyroid tumors in rats initiated
      with N-bis(2-hydroxypropyl)nitrosamine and the mechanism of action.
AB  - To cast light on whether xylazine hydrochloride (XZ), a veterinary medicine
      commonly used as a sedative agent for food-producing animals, has any promoting
      potential for thyroid carcinogenesis, the following studies were performed. In
      Experiment I, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ for
      52 weeks with or without initiation with 2400 mg/kg N:-bis(2
      hydroxypropyl)nitrosamine (DHPN). Focal follicular cell hyperplasias, adenomas
      and/or carcinomas were induced in the DHPN alone, XZ alone and DHPN+XZ groups,
      and the incidences and multiplicities of these lesions in the DHPN+XZ group were
      significantly increased as compared with the DHPN alone case. In Experiment II,
      male F344 rats received a diet containing 1000 or 0 p.p.m. XZ and were examined
      for serum levels of triiodothyronine (T(3)), thyroxine (T(4)) and thyroid
      stimulating hormone (TSH) at weeks 1, 2 and 4. In the XZ group, significant
      increase in thyroid weight and decrease in serum T(4) levels were observed at all
      time points. Serum T(3) and TSH levels were significantly decreased and
      increased, respectively, at week 1, but returned to within the control range
      thereafter. In Experiment III, male F344 rats received a diet containing 1000 or
      0 p.p.m. XZ, they were examined for thyroid iodine uptake and organification of
      XZ after 1 and 2 weeks. The thyroidal iodine uptake per milligram of thyroid and
      the amount of iodine bound to 1 mg protein showed a tendency for decrease at week
      1 and significant decrease at week 2. These results indicate that XZ has tumor
      promoting effects on thyroid follicular cells, and suggest an involvement of
      alterations in thyroid-related hormone levels due to inhibition of thyroid iodine
      uptake and organification, resulting, provably, in serum TSH stimulation
      depending on continuous reduction of serum T(4) level through the feedback system
      in the pituitary-thyroid axis.

PMID- 11285198
TI  - Intestinal toxicity and carcinogenic potential of the food mutagen 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in DNA repair deficient XPA-/- mice.
AB  - The effects of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) were studied in DNA repair deficient XPA(-/-) mice. The nullizygous XPA
      knockout mice, which lack a functional nucleotide excision repair (NER) pathway,
      were exposed to dietary concentrations ranging from 10 to 200 p.p.m. The results
      show that PhIP is extremely toxic to XPA(-/-) mice, even at doses 10-fold lower
      than tolerated by wild-type C57BL/6 mice. XPA(-/-) mice rapidly lost weight and
      died within 2 and 6 weeks upon administration of 200 and 100 p.p.m.,
      respectively. Intestinal abnormalities like distended and overfilled ileum and
      caecum, together with clear signs of starvation, suggests that the small
      intestines were the primary target tissue for the severe toxic effects. Mutation
      analysis in XPA(-/-) mice carrying a lacZ reporter gene, indicated that the
      observed toxicity of PhIP might be caused by genotoxic effects in the small
      intestine. LacZ mutant frequencies appeared to be selectively and dose
      dependently increased in the intestinal DNA of treated XPA(-/-) mice.
      Furthermore, DNA repair deficient XPC(-/-) mice, which are still able to repair
      DNA damage in actively transcribed genes, did not display any toxicity upon
      treatment with PhIP (100 p.p.m.). This suggests that transcription coupled repair
      of DNA damage (PhIP adducts) in active genes plays a crucial role in preventing
      the intestinal toxicity of PhIP. Finally, PhIP appeared to be carcinogenic for
      XPA(-/-) mice at subtoxic doses. Upon treatment of the mice for 6 months with 10
      or 25 p.p.m. PhIP, significantly increased tumour incidences were observed after
      a total observation period of one year. At 10 p.p.m. only lymphomas were found,
      whereas at 25 p.p.m. some intestinal tumours (adenomas and adenocarcinomas) were
      also observed.

PMID- 11285199
TI  - Oxidative damage and direct adducts in calf thymus DNA induced by the
      pentachlorophenol metabolites, tetrachlorohydroquinone and tetrachloro-1,4
      benzoquinone.
AB  - DNA damage induced by quinoid metabolites of pentachlorophenol (PCP), i.e.
      tetrachloro-1,4-benzoquinone (Cl(4)BQ) and tetrachlorohydroquinone (Cl(4)HQ), was
      investigated in calf thymus DNA. The (32)P-post-labeling assay revealed four
      major and several minor adducts (3.5 adducts per 10(5) total nucleotides) that
      were produced in calf thymus DNA treated with Cl(4)BQ (5 mM). These DNA adducts
      were chemically stable even after conditions that induce thermal depurination and
      are unlikely to undergo depurination/depyrimidination to form
      apurinic/apyrimidinic (AP) sites. In addition, increases in 8-hydroxy
      deoxyguanosine (8-HO-dG) (5 8-HO-dG per 10(5) nucleotides) and AP sites (0.5 AP
      sites per 10(5) nucleotides) were observed in Cl(4)BQ-modified calf thymus DNA.
      Further investigation indicated that in the presence of Cu(II) and NADPH, low
      concentrations of Cl(4)BQ (1 microM) induced a doubling of 8-HO-dG (10 8-HO-dG
      per 10(5) nucleotides) and dramatic increases in AP sites (20 AP sites per 10(5)
      nucleotides) and DNA single-strand breaks. The types of DNA damage induced by
      Cl(4)HQ plus Cu(II) were similar to those by Cl(4)BQ plus Cu(II) and NADPH,
      whereas catalase inhibited the formation of DNA damage. These data suggest that
      oxidative damage is causally involved in the formation of AP sites. Concentration
      dependent increases in 8-HO-dG induced by Cl(4)HQ plus Cu(II) and Cl(4)BQ plus
      Cu(II) and NADPH were correlated with the formation of AP sites (r(2) = 0.977)
      with a ratio of 8-HO-dG to AP sites at 1:1.6. The AP site-cleavage assay
      confirmed that approximately 85% of the AP sites induced by Cl(4)HQ and Cu(II)
      were detected as 5'-cleaved AP sites. Since hydrogen peroxide alone causes
      similar DNA damage, these results suggest the involvement of Cu(II) and hydrogen
      peroxide in the induction of oxidative DNA damage by Cl(4)HQ/Cl(4)BQ. The data
      demonstrate that PCP quinone and hydroquinone induce direct and oxidative base
      modifications as well as the formation of 5'-cleaved AP sites in genomic DNA.
      These lesions may have important implications for PCP clastogenicity and
      carcinogenicity.

PMID- 11285200
TI  - Induction of direct adducts, apurinic/apyrimidinic sites and oxidized bases in
      nuclear DNA of human HeLa S3 tumor cells by tetrachlorohydroquinone.
AB  - DNA damage induced by tetrachlorohydroquinone (Cl(4)HQ), the quinonoid metabolite
      of pentachlorophenol (PCP), was investigated in human HeLa S3 tumor cells.
      Formation of one major and two minor DNA adducts in cells treated with Cl(4)HQ
      (50-300 microM) was detected by (32)P-post-labeling assay and the adducts
      accumulated over the course of the experiment (0.5-2 h), with total adduct levels
      estimated to be 3-6 per 10(8) nucleotides. These adducts did not correspond to
      those derived from calf thymus DNA treated with tetrachloro-1,4-benzoquinone.
      Results from the apurinic/apyrimidinic (AP) sites assay indicated that the number
      of AP sites was 2-fold greater in cells exposed to Cl(4)HQ (300 microM) than the
      corresponding control. Further characterization of the AP sites confirmed that
      Cl(4)HQ induced predominantly (75%) putrescine-excisable AP sites in HeLa S3
      cells. In parallel, the concentration of 8-hydroxy-2'-deoxyguanosine (8-HO-dG) in
      cells treated with Cl(4)HQ for 0.5 and 2 h was increased 2- and 5-fold,
      respectively, compared with the control. The extent of oxidative DNA damage
      induced by Cl(4)HQ was approximately two orders of magnitude greater than those
      of direct DNA adducts. Overall, it appears that reactive oxygen species mediate
      the parallel formation of AP sites and 8-HO-dG in HeLa S3 cells following
      treatment with Cl(4)HQ and that the contribution of depurination/depyrimidination
      of direct DNA adducts is relatively insignificant compared with the formation of
      oxidized AP sites. We conclude that putrescine-excisable AP sites represent a
      major type of ROS-mediated oxidative DNA damage in cellular DNA induced by
      Cl(4)HQ and may play a role in PCP-induced clastogenicity in mammalian cells.

PMID- 11285201
TI  - Susceptibility of proliferating cells to benzo[a]pyrene-induced homologous
      recombination in mice.
AB  - The pink-eyed unstable mutation, p(un), is the result of a 70 kb tandem
      duplication within the murine pink-eyed, p, gene. Deletion of one copy of the
      duplicated region by homologous deletion/recombination occurs spontaneously in
      embryos and results in pigmented spots in the fur and eye. Such deletion events
      are inducible by a variety of DNA damaging agents, as we have observed previously
      with both fur- and eye-spot assays. Here we describe a study of the effect of
      exposure to benzo[a]pyrene (B[a]P) at different times of development on reversion
      induction in the eye. Previously we, among others, have reported that the retinal
      pigment epithelium (RPE) displays a position effect variegation phenotype in the
      pattern of pink-eyed unstable reversions. Following an acute exposure to B[a]P or
      X-rays on the tenth day of gestation an increased frequency of reversion events
      was detected in a distinct region of the adult RPE. Examining exposure at
      different times of eye development reveals that both B[a]P and X-rays result in
      an increased frequency of reversion events, though the increase was only
      significant following B[a]P exposure, similar to our previous report limited to
      exposure on the tenth day of gestation. Examination of B[a]P-exposed RPE in the
      present study revealed distinct regions where the induced events lie and that the
      positions of these regions are found at increasing distances from the optic nerve
      the later the time of exposure. This position effect directly reflects the
      previously observed developmental pattern of the RPE, namely that cells in the
      regions most distal from the optic nerve are proliferating most vigorously. The
      numbers and positions of RPE cells displaying the transformed (pigmented)
      phenotype strongly advocate the proposal that dividing cells are at highest risk
      to deletions induced by carcinogens.

PMID- 11285202
TI  - Age-dependent skin tumorigenesis and transgene expression in the Tg.AC (v-Ha-ras)
      transgenic mouse.
AB  - Transgenic Tg.AC (v-Ha-ras ) mice develop skin tumors in response to specific
      carcinogens and tumor promoters. The Tg.AC mouse carries the coding sequence of v
      Ha ras, linked to a zeta-globin promoter and an SV40 polyadenylation signal
      sequence. The transgene confers on these mice the property of genetically
      initiated skin. This study examines the age-dependent sensitivity of the
      incidence of skin papillomas in Tg.AC mice exposed to topically applied 12-O:
      tetradecanoylphorbol-13-acetate (TPA) treatment, full thickness skin wounding or
      UV radiation. Skin tumor incidence and multiplicity were strongly age-dependent,
      increasing with increasing age of the animal when first treated at 5, 10, 21 or
      32 weeks of age. Furthermore, the temporal induction of transgene expression in
      keratinocytes isolated from TPA-treated mouse skin was also influenced by the age
      of the mice. Transgene expression was seen as early as 14 days after the start of
      TPA treatment in mice that were 10-32 weeks of age, but was not detected in
      similarly treated 5-week old mice. When isolated keratinocytes were fractionated
      by density gradient centrifugation the highest transgene expression was found in
      the denser basal keratinocytes. Transgene expression could be detected in the
      denser keratinocyte fraction as early as 9 days from start of TPA treatment in 32
      week old mice. Using flow cytometry, a positive correlation was observed between
      expression of the v-Ha-ras transgene and enriched expression of the cell surface
      protein beta1-integrin, a putative marker of epidermal stem cells. This result
      suggests that, in the Tg.AC mouse, an age-dependent sensitivity to tumor
      promotion and the correlated induction of transgene expression are related to
      changes in cellular development in the follicular compartment of the skin.

PMID- 11285203
TI  - Repair of sulfur mustard-induced DNA damage in mammalian cells measured by a host
      cell reactivation assay.
AB  - DNA damage is thought to be the initial event that causes sulfur mustard (SM)
      toxicity, while the ability of cells to repair this damage is thought to provide
      a degree of natural protection. To investigate the repair process, we have
      damaged plasmids containing the firefly luciferase gene with either SM or its
      monofunctional analog, 2-chloroethyl ethyl sulfide (CEES). Damaged plasmids were
      transfected into wild-type and nucleotide excision repair (NER) deficient Chinese
      hamster ovary cells; these cells were also transfected with a second reporter
      plasmid containing RENILLA: luciferase as an internal control on the efficiency
      of transfection. Transfected cells were incubated at 37 degrees C for 27 h and
      then both firefly and RENILLA: luciferase intensities were measured on the same
      samples with the dual luciferase reporter assay. Bioluminescence in lysates from
      cells transfected with damaged plasmid, expressed as a percentage of the
      bioluminescence from cells transfected with undamaged plasmid, is increased by
      host cell repair activity. The results show that NER-competent cells have a
      higher reactivation capacity than NER-deficient cells for plasmids damaged by
      either SM or CEES. Significantly, NER-competent cells are also more resistant to
      the toxic effects of SM and CEES, indicating that NER is not only proficient in
      repairing DNA damage caused by either agent but also in decreasing their
      toxicity. This host cell repair assay can now be used to determine what other
      cellular mechanisms protect cells from mustard toxicity and under what conditions
      these mechanisms are most effective.

PMID- 11285204
TI  - Interleukin-10-deficient mice and inflammatory bowel disease associated cancer
      development.
AB  - Interleukin-10-deficient mice develop colitis and colorectal cancer similar to
      the inflammatory bowel disease associated cancer in humans. The aim of this study
      was to identify possible mutations of oncogenes and tumour suppressor genes
      involved in tumorigenesis in Interleukin-10 (IL-10)-deficient mice. Twenty colon
      carcinomas from IL-10-deficient mice were screened for mutations in the K-ras and
      p53 genes by 'cold' single-strand-conformation polymorphism. Immunohistochemical
      staining was performed to detect mutations in the proteins P53, APC and MSH2, and
      the transforming growth factor beta type II receptor. Microsatellite instability
      was analysed at eight chromosomal loci and plasma levels of transforming growth
      factor beta1 (TGF-beta1) were also measured. At 9 weeks, 14% of the animals
      developed colorectal cancer, and at 10-31 weeks the incidence of carcinoma was
      65%. No mutations were detected in the analysed oncogene and tumour suppressor
      genes. Plasma TGF-beta1 levels in IL-10-deficient mice 10-31 weeks old were
      higher than in wild-type littermates e.g. 45.7 +/- 4.6 ng/ml versus 19.8 +/- 4.5
      ng/ml (P<0.01). No alterations in K-ras, p53, APC: and Msh2 genes suggests that
      other genes are involved in the development of these tumours. Elevated TGF-beta1
      plasma levels correspond to the high incidence of dysplasia and cancer. Normal
      expression of the TGF-beta II receptors hints at genetic alterations in other
      members of the TGF-beta receptor signal transduction pathway.

PMID- 11285205
TI  - Cytochrome P4501A2 (CYP1A2) activity and lung cancer risk: a preliminary study
      among Chinese women in Singapore.
AB  - There is increasing evidence for the role of heterocyclic and other arylamines in
      carcinogenesis, including lung carcinogenesis. Chinese women have a high rate of
      lung cancer despite a low smoking prevalence, and studies in this population may
      provide useful information on risk factors other than smoking. Hepatic CYP1A2 and
      NAT2 are involved in the metabolism of carcinogenic arylamines, and NAT2 also
      catalyzes the detoxification pathway for these compounds. In this study, we
      examined the effect of CYP1A2 activity using a urinary caffeine metabolic ratio
      assay for 54 Chinese women with newly diagnosed lung cancer (including 28
      adenocarcinomas) and 174 hospital controls. Among them, NAT2 genotype was
      available for 47 cases and 98 controls. There was no effect of CYP1A2 activity on
      overall risk of lung cancer in the study population [odds ratio (OR) 0.8, 95%
      confidence interval (CI) 0.4-1.6, adjusted for age at diagnosis, smoking and
      cruciferous vegetable intake]. For adenocarcinomas, the OR was 1.5, 95% CI 0.6
      3.4. After further adjustment for NAT2 acetylator genotype, the OR for
      adenocarcinoma was 1.8 (95% CI 0.7-4.8). When the combined NAT2/CYP1A2 status was
      examined, women with slow NAT2 and rapid CYP1A2 activity were at highest risk
      (adjusted OR 6.9, 95% CI 1.3-37.6) relative to women with rapid NAT2 and slow
      CYP1A2 activity, for lung adenocarcinoma. While larger studies are needed to
      confirm or refute these results, they are consistent with a role for heterocyclic
      arylamines in lung carcinogenesis in this primarily non-smoking population.

PMID- 11285206
TI  - Re: Rajeswari,N., Ahuja,Y.R., Malani,U., Chandrashekar,S., Balakrishna,N.,
      Rao,K.V. and Khar,A. (2000) Risk assessment in the first degree female relatives
      of breast cancer patients using the alkaline Comet assay. Carcinogenesis, 21, 557
      561.

PMID- 11285213
TI  - Atomic structure of the major capsid protein of rotavirus: implications for the
      architecture of the virion.
AB  - The structural protein VP6 of rotavirus, an important pathogen responsible for
      severe gastroenteritis in children, forms the middle layer in the triple-layered
      viral capsid. Here we present the crystal structure of VP6 determined to 2 A
      resolution and describe its interactions with other capsid proteins by fitting
      the atomic model into electron cryomicroscopic reconstructions of viral
      particles. VP6, which forms a tight trimer, has two distinct domains: a distal
      beta-barrel domain and a proximal alpha-helical domain, which interact with the
      outer and inner layer of the virion, respectively. The overall fold is similar to
      that of protein VP7 from bluetongue virus, with the subunits wrapping about a
      central 3-fold axis. A distinguishing feature of the VP6 trimer is a central
      Zn(2+) ion located on the 3-fold molecular axis. The crude atomic model of the
      middle layer derived from the fit shows that quasi-equivalence is only partially
      obeyed by VP6 in the T = 13 middle layer and suggests a model for the assembly of
      the 260 VP6 trimers onto the T = 1 viral inner layer.

PMID- 11285214
TI  - Structural polymorphism of the major capsid protein of rotavirus.
AB  - Rotaviruses are important human pathogens with a triple-layered icosahedral
      capsid. The major capsid protein VP6 is shown here to self-assemble into
      spherical or helical particles mainly depending upon pH. Assembly is inhibited
      either by low pH (<3.0) or by a high concentration (>100 mM) of divalent cations
      (Ca(2+) and Zn(2+)). The structures of two types of helical tubes were determined
      by electron cryomicroscopy and image analysis to a resolution of 2.0 and 2.5 nm.
      In both reconstructions, the molecular envelope of VP6 fits the atomic model
      determined by X-ray crystallography remarkably well. The 3-fold symmetry of the
      VP6 trimer, being incompatible with the helical symmetry, is broken at the level
      of the trimer contacts. One type of contact is maintained within all VP6
      particles (tubes and virus), strongly suggesting that VP6 assemblies arise from
      different packings of a unique dimer of trimers. Our data show that the
      protonation state and thus the charge distribution are important switches
      governing the assembly of macromolecular assemblies.

PMID- 11285215
TI  - Cpx signaling pathway monitors biogenesis and affects assembly and expression of
      P pili.
AB  - P pili are important virulence factors in uropathogenic Escherichia coli. The Cpx
      two-component signal transduction system controls a stress response and is
      activated by misfolded proteins in the periplasm. We have discovered new
      functions for the Cpx pathway, indicating that it may play a critical role in
      pathogenesis. P pili are assembled via the chaperone/usher pathway. Subunits that
      go 'OFF-pathway' during pilus biogenesis generate a signal. This signal is
      derived from the misfolding and aggregation of subunits that failed to come into
      contact with the chaperone in the periplasm. In response, Cpx not only controls
      the stress response, but also controls genes necessary for pilus biogenesis, and
      is involved in regulating the phase variation of pap expression and, potentially,
      the expression of a panoply of other virulence factors. This study demonstrates
      how the prototypic chaperone/usher pathway is intricately linked and dependent
      upon a signal transduction system.

PMID- 11285216
TI  - The hairpin structure of the (6)F1(1)F2(2)F2 fragment from human fibronectin
      enhances gelatin binding.
AB  - The solution structure of the (6)F1(1)F2(2)F2 fragment from the gelatin-binding
      region of fibronectin has been determined (Protein Data Bank entry codes 1e88 and
      1e8b). The structure reveals an extensive hydrophobic interface between the non
      contiguous (6)F1 and (2)F2 modules. The buried surface area between (6)F1 and
      (2)F2 ( approximately 870 A(2)) is the largest intermodule interface seen in
      fibronectin to date. The dissection of (6)F1(1)F2(2)F2 into the (6)F1(1)F2 pair
      and (2)F2 results in near-complete loss of gelatin-binding activity. The hairpin
      topology of (6)F1(1)F2(2)F2 may facilitate intramolecular contact between the
      matrix assembly regions flanking the gelatin-binding domain. This is the first
      high-resolution study to reveal a compact, globular arrangement of modules in
      fibronectin. This arrangement is not consistent with the view that fibronectin is
      simply a linear 'string of beads'.

PMID- 11285217
TI  - Crystal structure of isopentenyl diphosphate:dimethylallyl diphosphate isomerase.
AB  - Isopentenyl diphosphate:dimethylallyl diphosphate (IPP:DMAPP) isomerase catalyses
      a crucial activation step in the isoprenoid biosynthesis pathway. This enzyme is
      responsible for the isomerization of the carbon-carbon double bond of IPP to
      create the potent electrophile DMAPP. DMAPP then alkylates other molecules,
      including IPP, to initiate the extraordinary variety of isoprenoid compounds
      found in nature. The crystal structures of free and metal-bound Escherichia coli
      IPP isomerase reveal critical active site features underlying its catalytic
      mechanism. The enzyme requires one Mn(2+) or Mg(2+) ion to fold in its active
      conformation, forming a distorted octahedral metal coordination site composed of
      three histidines and two glutamates and located in the active site. Two critical
      residues, C67 and E116, face each other within the active site, close to the
      metal-binding site. The structures are compatible with a mechanism in which the
      cysteine initiates the reaction by protonating the carbon-carbon double bond,
      with the antarafacial rearrangement ultimately achieved by one of the glutamates
      involved in the metal coordination sphere. W161 may stabilize the highly reactive
      carbocation generated during the reaction through quadrupole- charge interaction.

PMID- 11285218
TI  - Elevated Cu/Zn-SOD exacerbates radiation sensitivity and hematopoietic
      abnormalities of Atm-deficient mice.
AB  - Patients with the genetic disorder ataxia-telangiectasia (A-T) display a
      pleiotropic phenotype that includes neurodegeneration, immunodeficiency, cancer
      predisposition and hypersensitivity to ionizing radiation. The gene responsible
      is ATM, and ATM:-knockout mice recapitulate most features of A-T. In order to
      study the involvement of oxidative stress in the A-T phenotype, we examined mice
      deficient for Atm and overexpressing human Cu/Zn superoxide dismutase (SOD1). We
      report that elevated levels of SOD1 exacerbate specific features of the murine
      Atm- deficient phenotype, including abnormalities in hematopoiesis and
      radiosensitivity. The data are consistent with the possibility that oxidative
      stress contributes to some of the clinical features associated with the A-T
      phenotype.

PMID- 11285219
TI  - Immobilized prion protein undergoes spontaneous rearrangement to a conformation
      having features in common with the infectious form.
AB  - It is hypothesized that infectious prions are generated as the cellular form of
      the prion protein (PrP(C)) undergoes pronounced conformational change under the
      direction of an infectious PrP(Sc) template. Conversion to the infectious
      conformer is particularly associated with major structural rearrangement in the
      central portion of the protein (residues 90-120), which has an extended flexible
      structure in the PrP(C) isoform. Using a panel of recombinant antibodies reactive
      with different parts of PrP, we show that equivalent major structural
      rearrangements occur spontaneously in this region of PrP immobilized on a
      surface. In contrast, regions more towards the termini of the protein remain
      relatively unaltered. The rearrangements occur even under conditions where
      individual PrP molecules should not contact one another. The propensity of
      specific unstructured regions of PrP to spontaneously undergo large and
      potentially deleterious conformational changes may have important implications
      for prion biology.

PMID- 11285220
TI  - Turning a disulfide isomerase into an oxidase: DsbC mutants that imitate DsbA.
AB  - There are two distinct pathways for disulfide formation in prokaryotes. The DsbA
      DsbB pathway introduces disulfide bonds de novo, while the DsbC-DsbD pathway
      functions to isomerize disulfides. One of the key questions in disulfide biology
      is how the isomerase pathway is kept separate from the oxidase pathway in vivo.
      Cross-talk between these two systems would be mutually destructive. To force
      communication between these two systems we have selected dsbC mutants that
      complement a dsbA null mutation. In these mutants, DsbC is present as a monomer
      as compared with dimeric wild-type DsbC. Based on these findings we rationally
      designed DsbC mutants in the dimerization domain. All of these mutants are able
      to rescue the dsbA null phenotype. Rescue depends on the presence of DsbB, the
      native re-oxidant of DsbA, both in vivo and in vitro. Our results suggest that
      dimerization acts to protect DsbC's active sites from DsbB-mediated oxidation.
      These results explain how oxidative and reductive pathways can co-exist in the
      periplasm of Escherichia coli.

PMID- 11285221
TI  - Dynamic localization cycle of the cell division regulator MinE in Escherichia
      coli.
AB  - The MinC protein directs placement of the division septum to the middle of
      Escherichia coli cells by blocking assembly of the division apparatus at other
      sites. MinD and MinE regulate MinC activity by modulating its cellular location
      in a unique fashion. MinD recruits MinC to the membrane, and MinE induces
      MinC/MinD to oscillate rapidly between the membrane of opposite cell halves.
      Using fixed cells, we previously found that a MinE-green fluorescent protein
      fusion accumulated in an annular structure at or near the midcell, as well as
      along the membrane on only one side of the ring. Here we show that in living
      cells, MinE undergoes a rapid localization cycle that appears coupled to MinD
      oscillation. The results show that MinE is not a fixed marker for septal ring
      assembly. Rather, they support a model in which MinE stimulates the removal of
      MinD from the membrane in a wave-like fashion. These waves run from a midcell
      position towards the poles in an alternating sequence such that the time-averaged
      concentration of division inhibitor is lowest at midcell.

PMID- 11285222
TI  - Signal peptide cleavage of a type I membrane protein, HCMV US11, is dependent on
      its membrane anchor.
AB  - The human cytomegalovirus (HCMV) US11 polypeptide is a type I membrane
      glycoprotein that targets major histocompatibility complex (MHC) class I
      molecules for destruction in a proteasome-dependent manner. Although the US11
      signal sequence appears to be a classical N-terminal signal peptide in terms of
      its sequence and cleavage site, a fraction of newly synthesized US11 molecules
      retain the signal peptide after the N-linked glycan has been attached and
      translation of the US11 polypeptide has been completed. Delayed cleavage of the
      US11 signal peptide is determined by the first four residues, the so-called n
      region of the signal peptide. Its replacement with the four N-terminal residues
      of the H-2K(b) signal sequence eliminates delayed cleavage. Surprisingly, a
      second region that affects the rate and extent of signal peptide cleavage is the
      transmembrane region close to the C-terminus of US11. Deletion of the
      transmembrane region of US11 (US11-180) significantly delays processing, a delay
      overcome by replacement with the H-2K(b) signal sequence. Thus, elements at a
      considerable distance from the signal sequence affect its cleavage.

PMID- 11285223
TI  - GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins
      in the recycling endosomal compartment.
AB  - Glycosylphosphatidylinositol (GPI) anchoring is important for the function of
      several proteins in the context of their membrane trafficking pathways. We have
      shown previously that endocytosed GPI-anchored proteins (GPI-APs) are recycled to
      the plasma membrane three times more slowly than other membrane components.
      Recently, we found that GPI-APs are delivered to endocytic organelles, devoid of
      markers of the clathrin-mediated pathway, prior to their delivery to a common
      recycling endosomal compartment (REC). Here we show that the rate-limiting step
      in the recycling of GPI-APs is their slow exit from the REC; replacement of the
      GPI anchor with a transmembrane protein sequence abolishes retention in this
      compartment. Depletion of endogenous sphingolipid levels using sphingolipid
      synthesis inhibitors or in a sphingolipid-synthesis mutant cell line specifically
      enhances the rate of endocytic recycling of GPI-APs to that of other membrane
      components. We have shown previously that endocytic retention of GPI-APs is also
      relieved by cholesterol depletion. These findings strongly suggest that
      functional retention of GPI-APs in the REC occurs via their association with
      sphingolipid and cholesterol-enriched sorting platforms or 'rafts'.

PMID- 11285224
TI  - Mechanism for down-regulation of CD28 by Nef.
AB  - SIV and HIV Nef proteins disrupt T-cell receptor machinery by down-modulating
      cell surface expression of CD4 and expression or signaling of CD3-TCR. Nef also
      down-modulates class I major histocompatibility complex (MHC) surface expression.
      We show that SIV and HIV-1 Nefs down-modulate CD28, a major co-stimulatory
      receptor that mediates effective T-cell activation, by accelerating CD28
      endocytosis. The effects of Nef on CD28, CD4, CD3 and class I MHC expression are
      all genetically separable, indicating that all are selected independently. In
      cells expressing a Nef-green fluorescent protein (GFP) fusion, CD28 co-localizes
      with the AP-2 clathrin adaptor and Nef-GFP. Mutations that disrupt Nef
      interaction with AP-2 disrupt CD28 down-regulation. Furthermore, HIV and SIV Nefs
      use overlapping but distinct target sites in the membrane-proximal region of the
      CD28 cytoplasmic domain. Thus, Nef probably induces CD28 endocytosis via the AP-2
      pathway, and this involves a ternary complex containing Nef, AP-2 and CD28. The
      likely consequence of the concerted down-regulation of CD28, CD4 and/or CD3 by
      Nef is disruption of antigen-specific signaling machineries in infected T cells
      following a productive antigen recognition event.

PMID- 11285225
TI  - An unusual C(2)-domain in the active-zone protein piccolo: implications for
      Ca(2+) regulation of neurotransmitter release.
AB  - Ca(2+) regulation of neurotransmitter release is thought to require multiple
      Ca(2+) sensors with distinct affinities. However, no low-affinity Ca(2+) sensor
      has been identified at the synapse. We now show that piccolo/aczonin, a recently
      described active-zone protein with C-terminal C(2)A- and C(2)B-domains,
      constitutes a presynaptic low-affinity Ca(2+) sensor. Ca(2+) binds to piccolo by
      virtue of its C(2)A-domain via an unusual mechanism that involves a large
      conformational change. The distinct Ca(2+)-binding properties of the piccolo
      C(2)A- domain are mediated by an evolutionarily conserved sequence at the bottom
      of the C(2)A-domain, which may fold back towards the Ca(2+)-binding sites on the
      top. Point mutations in this bottom sequence inactivate it, transforming low
      affinity Ca(2+) binding (100-200 microM in the presence of phospholipids) into
      high-affinity Ca(2+) binding (12-14 microM). The unusual Ca(2+)-binding mode of
      the piccolo C(2)A-domain reveals that C(2)-domains are mechanistically more
      versatile than previously envisaged. The low Ca(2+) affinity of the piccolo C(2)A
      domain suggests that piccolo could function in short-term synaptic plasticity
      when Ca(2+) concentrations accumulate during repetitive stimulation.

PMID- 11285226
TI  - The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac- and Rab
      dependent pathways.
AB  - Dictyostelium discoideum DdRacGap1 (DRG) contains both Rho-GEF and Rho-GAP
      domains, a feature it shares with mammalian Bcr and Abr. To elucidate the
      physiological role of this multifunctional protein, we characterized the
      enzymatic activity of recombinant DRG fragments in vitro, created DRG-null cells,
      and studied the function of the protein in vivo by analysing the phenotypic
      changes displayed by DRG-depleted cells and DRG-null cells complemented with DRG
      or DRG fragments. Our results show that DRG-GEF modulates F-actin dynamics and
      cAMP-induced F-actin formation via Rac1-dependent signalling pathways. DRG's RacE
      GAP activity is required for proper cytokinesis to occur. Additionally, we
      provide evidence that the specificity of DRG is not limited to members of the Rho
      family of small GTPases. A recombinant DRG-GAP accelerates the GTP hydrolysis of
      RabD 30-fold in vitro and our complementation studies show that DRG-GAP activity
      is required for the RabD-dependent regulation of the contractile vacuole system
      in Dictyostelium.

PMID- 11285227
TI  - COP9 signalosome-specific phosphorylation targets p53 to degradation by the
      ubiquitin system.
AB  - In higher eukaryotic cells, the p53 protein is degraded by the ubiquitin-26S
      proteasome system mediated by Mdm2 or the human papilloma virus E6 protein. Here
      we show that COP9 signalosome (CSN)-specific phosphorylation targets human p53 to
      ubiquitin-26S proteasome-dependent degradation. As visualized by electron
      microscopy, p53 binds with high affinity to the native CSN complex. p53 interacts
      via its N-terminus with CSN subunit 5/Jab1 as shown by far-western and pull-down
      assays. The CSN-specific phosphorylation sites were mapped to the core domain of
      p53 including Thr155. A phosphorylated peptide, Deltap53(145-164), specifically
      inhibits CSN-mediated phosphorylation and p53 degradation. Curcumin, a CSN kinase
      inhibitor, blocks E6-dependent p53 degradation in reticulocyte lysates. Mutation
      of Thr155 to valine is sufficient to stabilize p53 against E6-dependent
      degradation in reticulocyte lysates and to reduce binding to Mdm2. The p53T155V
      mutant accumulates in both HeLa and HL 60 cells and exhibits a mutant (PAb 240+)
      conformation. It induces the cyclin-dependent inhibitor p21. In HeLa and MCF-7
      cells, inhibition of CSN kinase by curcumin or Deltap53(145-164) results in
      accumulation of endogenous p53.

PMID- 11285228
TI  - Regulated secretion of neurotrophins by metabotropic glutamate group I (mGluRI)
      and Trk receptor activation is mediated via phospholipase C signalling pathways.
AB  - Neurotrophins (NTs) play an essential role in modulating activity-dependent
      neuronal plasticity. In this context, the site and extent of NT secretion are of
      crucial importance. Here, we demonstrate that the activation of phospolipase C
      (PLC) and the subsequent mobilization of Ca(2+) from intracellular stores are
      essential for NT secretion initiated by both Trk and glutamate receptor
      activation. Mutational analysis of tyrosine residues, highly conserved in the
      cytoplasmic domain of all Trk receptors, revealed that the activation of PLC
      gamma in cultured hippocampal neurons and nnr5 cells is necessary to mobilize
      Ca(2+) from intracellular stores, the key mechanism for regulated NT secretion. A
      similar signalling mechanism has been identified for glutamate-mediated NT
      secretion-which in part depends on the activation of PLC via metabotropic
      receptors-leading to the mobilization of Ca(2+) from internal stores by inositol
      trisphosphate. Thus, PLC-mediated signal transduction pathways are the common
      mechanisms for both Trk- and mGluRI-mediated NT secretion.

PMID- 11285229
TI  - A novel mechanism of PKA anchoring revealed by solution structures of anchoring
      complexes.
AB  - The specificity of intracellular signaling events is controlled, in part, by
      compartmentalization of protein kinases and phosphatases. The subcellular
      localization of these enzymes is often maintained by protein- protein
      interactions. A prototypic example is the compartmentalization of the cAMP
      dependent protein kinase (PKA) through its association with A-kinase anchoring
      proteins (AKAPs). A docking and dimerization domain (D/D) located within the
      first 45 residues of each regulatory (R) subunit protomer forms a high affinity
      binding site for its anchoring partner. We now report the structures of two D/D
      AKAP peptide complexes obtained by solution NMR methods, one with Ht31(493-515)
      and the other with AKAP79(392-413). We present the first direct structural data
      demonstrating the helical nature of the peptides. The structures reveal conserved
      hydrophobic interaction surfaces on the helical AKAP peptides and the PKA R
      subunit, which are responsible for mediating the high affinity association in the
      complexes. In a departure from the dimer-dimer interactions seen in other X-type
      four-helix bundle dimeric proteins, our structures reveal a novel hydrophobic
      groove that accommodates one AKAP per RIIalpha D/D.

PMID- 11285230
TI  - Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I
      receptor-deficient mice.
AB  - Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice has
      previously suggested that it regulates both hematopoiesis and angiogenesis. To
      define the function of TGF-beta more precisely, we inactivated the TGF-beta type
      I receptor (TbetaRI) gene by gene targeting. Mice lacking TbetaRI die at
      midgestation, exhibiting severe defects in vascular development of the yolk sac
      and placenta, and an absence of circulating red blood cells. However, despite
      obvious anemia in the TbetaRI(-/-) yolk sacs, clonogenic assays on yolk sac
      derived hematopoietic precursors in vitro revealed that TbetaRI(-/-) mice exhibit
      normal hematopoietic potential compared with wild-type and heterozygous siblings.
      Endothelial cells derived from TbetaRI-deficient embryos show enhanced cell
      proliferation, improper migratory behavior and impaired fibronectin production in
      vitro, defects that are associated with the vascular defects seen in vivo. We
      thus demonstrate here that, while TbetaRI is crucial for the function of TGF-beta
      during vascular development and can not be compensated for by the activin
      receptor-like kinase-1 (ALK-1), functional hematopoiesis and development of
      hematopoietic progenitors is not dependent on TGF-beta signaling via TbetaRI.

PMID- 11285231
TI  - Ca(2+)-sensor region of IP(3) receptor controls intracellular Ca(2+) signaling.
AB  - Many important cell functions are controlled by Ca(2+) release from intracellular
      stores via the inositol 1,4,5-trisphosphate receptor (IP(3)R), which requires
      both IP(3) and Ca(2+) for its activity. Due to the Ca(2+) requirement, the IP(3)R
      and the cytoplasmic Ca(2+) concentration form a positive feedback loop, which has
      been assumed to confer regenerativity on the IP(3)-induced Ca(2+) release and to
      play an important role in the generation of spatiotemporal patterns of Ca(2+)
      signals such as Ca(2+) waves and oscillations. Here we show that glutamate 2100
      of rat type 1 IP(3)R (IP(3)R1) is a key residue for the Ca(2+) requirement.
      Substitution of this residue by aspartate (E2100D) results in a 10-fold decrease
      in the Ca(2+) sensitivity without other effects on the properties of the IP(3)R1.
      Agonist-induced Ca(2+) responses are greatly diminished in cells expressing the
      E2100D mutant IP(3)R1, particularly the rate of rise of initial Ca(2+) spike is
      markedly reduced and the subsequent Ca(2+) oscillations are abolished. These
      results demonstrate that the Ca(2+) sensitivity of the IP(3)R is functionally
      indispensable for the determination of Ca(2+) signaling patterns.

PMID- 11285232
TI  - Molecular basis of thermosensing: a two-component signal transduction thermometer
      in Bacillus subtilis.
AB  - Both prokaryotes and eukaryotes respond to a decrease in temperature with the
      expression of a specific subset of proteins. Although a large body of information
      concerning cold shock-induced genes has been gathered, studies on temperature
      regulation have not clearly identified the key regulatory factor(s) responsible
      for thermosensing and signal transduction at low temperatures. Here we identified
      a two-component signal transduction system composed of a sensor kinase, DesK, and
      a response regulator, DesR, responsible for cold induction of the des gene coding
      for the Delta5-lipid desaturase from Bacillus subtilis. We found that DesR binds
      to a DNA sequence extending from position -28 to -77 relative to the start site
      of the temperature-regulated des gene. We show further that unsaturated fatty
      acids (UFAs), the products of the Delta5-desaturase, act as negative signalling
      molecules of des transcription. Thus, a regulatory loop composed of the DesK-DesR
      two-component signal transduction system and UFAs provides a novel mechanism for
      the control of gene expression at low temperatures.

PMID- 11285233
TI  - The ciliary neurotrophic factor receptor alpha component induces the secretion of
      and is required for functional responses to cardiotrophin-like cytokine.
AB  - Ciliary neurotrophic factor (CNTF) is involved in the survival of a number of
      different neural cell types, including motor neurons. CNTF functional responses
      are mediated through a tripartite membrane receptor composed of two signalling
      receptor chains, gp130 and the leukaemia inhibitory factor receptor (LIFR),
      associated with a non-signalling CNTF binding receptor alpha component (CNTFR).
      CNTFR-deficient mice show profound neuronal deficits at birth, leading to a
      lethal phenotype. In contrast, inactivation of the CNTF gene leads only to a
      slight muscle weakness, mainly during adulthood, suggesting that CNTFR binds to a
      second ligand that is important for development. Modelling studies of the
      interleukin-6 family member cardiotrophin-like cytokine (CLC) revealed structural
      similarities with CNTF, including the conservation of a site I domain involved in
      binding to CNTFR. Co-expression of CLC and CNTFR in mammalian cells generates a
      secreted composite cytokine, displaying activities on cells expressing the gp130
      LIFR complex on their surface. Correspondingly, CLC-CNTFR activates gp130, LIFR
      and STAT3 signalling components, and enhances motor neuron survival. Together,
      these observations demonstrate that CNTFR induces the secretion of CLC, as well
      as mediating the functional responses of CLC.

PMID- 11285234
TI  - A family of snail-related zinc finger proteins regulates two distinct and
      parallel mechanisms that mediate Drosophila neuroblast asymmetric divisions.
AB  - Three snail family genes snail, escargot and worniu, encode related zinc finger
      transcription factors that mediate Drosophila central nervous system (CNS)
      development. We show that simultaneous removal of all three genes causes
      defective neuroblast asymmetric divisions; inscuteable transcription/translation
      is delayed/suppressed in the segmented CNS. Further more, defects in localization
      of cell fate determinants and orientation of the mitotic spindle in dividing
      neuroblasts are much stronger than those associated with inscuteable loss of
      function. In inscuteable neuroblasts, cell fate determinants are mislocalized
      during prophase and metaphase, yet during anaphase and telophase the great
      majority of mutant neuroblasts localize these determinants as cortical crescents
      overlying one of the spindle poles. This phenomenon, known as 'telophase rescue',
      does not occur in the absence of the snail family genes; moreover, in contrast to
      inscuteable mutants, mitotic spindle orientation is completely randomized. Our
      data provide further evidence for the existence of two distinct asymmetry
      controlling mechanisms in neuroblasts both of which require snail family gene
      function: an inscuteable-dependent mechanism that functions throughout mitosis
      and an inscuteable-independent mechanism that acts during anaphase/telophase.

PMID- 11285235
TI  - Transcriptional repression and developmental functions of the atypical vertebrate
      GATA protein TRPS1.
AB  - Known vertebrate GATA proteins contain two zinc fingers and are required in
      development, whereas invertebrates express a class of essential proteins
      containing one GATA-type zinc finger. We isolated the gene encoding TRPS1, a
      vertebrate protein with a single GATA-type zinc finger. TRPS1 is highly conserved
      between Xenopus and mammals, and the human gene is implicated in dominantly
      inherited tricho-rhino-phalangeal (TRP) syndromes. TRPS1 is a nuclear protein
      that binds GATA sequences but fails to transactivate a GATA-dependent reporter.
      Instead, TRPS1 potently and specifically represses transcriptional activation
      mediated by other GATA factors. Repression does not occur from competition for
      DNA binding and depends on a C-terminal region related to repressive domains
      found in Ikaros proteins. During mouse development, TRPS1 expression is prominent
      in sites showing pathology in TRP syndromes, which are thought to result from
      TRPS1 haploinsufficiency. We show instead that truncating mutations identified in
      patients encode dominant inhibitors of wild-type TRPS1 function, suggesting an
      alternative mechanism for the disease. TRPS1 is the first example of a GATA
      protein with intrinsic transcriptional repression activity and possibly a
      negative regulator of GATA-dependent processes in vertebrate development.

PMID- 11285236
TI  - The site of HIV-1 integration in the human genome determines basal
      transcriptional activity and response to Tat transactivation.
AB  - Because of the heterogeneity of chromatin, the site of integration of human
      immunodeficiency virus (HIV) in the genome could have dramatic effects on its
      transcriptional activity. We have used an HIV-1-derived retroviral vector, in
      which the green fluorescent protein is under the control of the HIV promoter, to
      generate by infection 34 Jurkat clonal cell lines each containing a single
      integration of the HIV-1 vector. In the absence of Tat, a 75-fold difference in
      expression level between the highest and lowest expressing clones was observed.
      Basal promoter activity was low in 80% of the clones and moderate to high in the
      remaining 20% of clones. We found that differences in expression levels are due
      to the integration site and are not controlled by DNA methylation or histone
      acetylation. Tat activated transcription in each clone, and an inverse
      correlation was observed between basal transcriptional activity and inducibility
      by Tat. These observations demonstrate that the chromatin environment influences
      basal HIV gene expression and that the HIV Tat protein activates transcription
      independently of the chromatin environment.

PMID- 11285238
TI  - LAP2 binds to BAF.DNA complexes: requirement for the LEM domain and modulation by
      variable regions.
AB  - LAP2 belongs to a family of nuclear membrane proteins sharing a 43 residue LEM
      domain. All LAP2 isoforms have the same N-terminal 'constant' region (LAP2-c),
      which includes the LEM domain, plus a C-terminal 'variable' region. LAP2-c
      polypeptide inhibits nuclear assembly in Xenopus extracts, and binds in vitro to
      barrier-to-autointegration factor (BAF), a DNA-bridging protein. We tested 17
      Xenopus LAP2-c mutants for nuclear assembly inhibition, and binding to BAF and
      BAF small middle dotDNA complexes. LEM domain mutations disrupted all activities
      tested. Some mutations outside the LEM domain had no effect on binding to BAF,
      but disrupted activity in Xenopus extracts, suggesting that LAP2-c has an
      additional unknown function required to inhibit nuclear assembly. Mutagenesis
      results suggest that BAF changes conformation when complexed with DNA. The
      binding affinity of LAP2 was higher for BAF small middle dotDNA complexes than
      for BAF, suggesting that these interactions are physiologically relevant.
      Nucleoplasmic domains of Xenopus LAP2 isoforms varied 9-fold in their affinities
      for BAF, but all isoforms supershifted BAF small middle dotDNA complexes. We
      propose that the LEM domain is a core BAF-binding domain that can be modulated by
      the variable regions of LAP2 isoforms.

PMID- 11285237
TI  - A role for histone deacetylase HDAC1 in modulating the transcriptional activity
      of MyoD: inhibition of the myogenic program.
AB  - The molecular mechanism(s) that are responsible for suppressing MyoD's
      transcriptional activities in undifferentiated skeletal muscle cells have not yet
      been determined. We now show that MyoD associates with a histone deacetylase-1
      (HDAC1) in these cells and that this interaction is responsible for silencing
      MyoD-dependent transcription of endogenous p21 as well as muscle-specific genes.
      Specifically, we present evidence that HDAC1 can bind directly to MyoD and use an
      acetylated MyoD as a substrate in vitro, whereas a mutant version of HDAC1
      (H141A) can not. Further more, this mutant also fails to repress MyoD-mediated
      transcription in vivo, and unlike wild-type HDAC1 it can not inhibit myogenic
      conversion, as judged by confocal microscopy. Finally, we show that an endogenous
      MyoD can be acetylated upon its conversion to a hypophosphorylated state and only
      when the cells have been induced to differentiate. These results provide for a
      model which postulates that MyoD may be co-dependent on HDAC1 and P/CAF for
      temporally controlling its transcriptional activity before and after the
      differentiation of muscle cells.

PMID- 11285239
TI  - Identification of an RNA-protein complex involved in chloroplast group II intron
      trans-splicing in Chlamydomonas reinhardtii.
AB  - In Chlamydomonas reinhardtii, the psaA mRNA is assembled by a process involving
      trans-splicing of separate transcripts, encoded at three separate loci of the
      chloroplast genome. At least 14 nuclear loci and one chloroplast gene, tscA, are
      needed for this process. We have cloned Raa3, the first nuclear gene implicated
      in the splicing of intron 1. The predicted sequence of Raa3 consists of 1783
      amino acids and shares a small region of homology with pyridoxamine 5'-phosphate
      oxidases. Raa3 is present in the soluble fraction of the chloroplast and is part
      of a large 1700 kDa complex, which also contains tscA RNA and the first psaA exon
      transcript. These partners, in association with other factors, form a chloroplast
      RNP particle that is required for the splicing of the first intron of psaA and
      which may be the counterpart of eukaryotic snRNPs involved in nuclear splicing.

PMID- 11285240
TI  - Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9
      skipping.
AB  - Alternative splicing of human cystic fibrosis transmembrane conductance regulator
      (CFTR) exon 9 is regulated by a combination of cis-acting elements distributed
      through the exon and both flanking introns (IVS8 and IVS9). Several studies have
      identified in the IVS8 intron 3' splice site a regulatory element that is
      composed of a polymorphic (TG)m(T)n repeated sequence. At present, no cellular
      factors have been identified that recognize this element. We have identified TDP
      43, a nuclear protein not previously described to bind RNA, as the factor binding
      specifically to the (TG)m sequence. Transient TDP-43 overexpression in Hep3B
      cells results in an increase in exon 9 skipping. This effect is more pronounced
      with concomitant overexpression of SR proteins. Antisense inhibition of
      endogenous TDP-43 expression results in increased inclusion of exon 9, providing
      a new therapeutic target to correct aberrant splicing of exon 9 in CF patients.
      The clinical and biological relevance of this finding in vivo is demonstrated by
      our characterization of a CF patient carrying a TG10T9(DeltaF508)/TG13T3(wt)
      genotype leading to a disease-causing high proportion of exon 9 skipping.

PMID- 11285241
TI  - SC35 autoregulates its expression by promoting splicing events that destabilize
      its mRNAs.
AB  - SC35 belongs to the family of SR proteins that regulate alternative splicing in a
      concentration-dependent manner in vitro and in vivo. We previously reported that
      SC35 is expressed through alternatively spliced mRNAs with differing 3'
      untranslated sequences and stabilities. Here, we show that overexpression of SC35
      in HeLa cells results in a significant decrease of endogenous SC35 mRNA levels
      along with changes in the relative abundance of SC35 alternatively spliced mRNAs.
      Remarkably, SC35 leads to both an exon inclusion and an intron excision in the 3'
      untranslated region of its mRNAs. In vitro splicing experiments performed with
      recombinant SR proteins demonstrate that SC35, but not ASF/SF2 or 9G8,
      specifically activates these alternative splicing events. Interestingly, the
      resulting mRNA is very unstable and we present evidence that mRNA surveillance is
      likely to be involved in this instability. SC35 therefore constitutes the first
      example of a splicing factor that controls its own expression through activation
      of splicing events leading to expression of unstable mRNA.

PMID- 11285242
TI  - An in vitro evolved precursor tRNA with aminoacylation activity.
AB  - A set of catalysts for aminoacyl-tRNA synthesis is an essential component for
      translation. The RNA world hypothesis postulates that RNA catalysts could have
      played this role. Here we show an in vitro evolved precursor tRNA consisting of
      two domains, a catalytic 5'-leader sequence and an aminoacyl-acceptor tRNA. The
      5'-leader sequence domain selectively self-charges phenylalanine on the 3'
      terminus of the tRNA domain. This cis-acting ribozyme is susceptible to RNase P
      RNA, generating the corresponding 5'-leader segment and the mature tRNA.
      Moreover, the 5'-leader segment is able to aminoacylate the mature tRNA in trans.
      Mutational studies have revealed that C(74) and C(75) at the tRNA aminoacyl
      acceptor end form base pairs with G71 and G70 of the trans-acting ribozyme. Such
      Watson-Crick base pairing with tRNA has been observed in RNase P RNA and 23S
      rRNA, suggesting that all three ribozymes use a similar mechanism for the
      recognition of the aminoacyl-acceptor end. Our demonstrations indicate that
      catalytic precursor tRNAs could have provided the foundations for the genetic
      coding system in the proto-translation system.

PMID- 11285243
TI  - Replication and preferential inheritance of hypersuppressive petite mitochondrial
      DNA.
AB  - Wild-type yeast mitochondrial DNA (mtDNA) is inherited biparentally, whereas
      mtDNA of hypersuppressive petite mutants is inherited uniparentally in crosses to
      strains with wild-type mtDNA. Genomes of hypersuppressive petites contain a
      conserved ori sequence that includes a promoter, but it is unclear whether the
      ori confers a segregation or replication advantage. Fluorescent in situ
      hybridization analysis of wild-type and petite mtDNAs in crosses reveals no
      preferential segregation of hypersuppressive petite mtDNA to first zygotic buds.
      We identify single-stranded DNA circles and RNA-primed DNA replication
      intermediates in hypersuppressive petite mtDNA that are absent from non
      hypersuppressive petites. Mutating the promoter blocks hypersuppressiveness in
      crosses to wild-type strains and eliminates the distinctive replication
      intermediates. We propose that promoter-dependent RNA-primed replication accounts
      for the uniparental inheritance of hypersuppressive petite mtDNA.

PMID- 11285244
TI  - Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may
      be caused by parental somatic recombination.
AB  - We report on the prevalence of mutations in the zinc finger transcription factor
      gene, ZIC2, in a group of 509 unrelated individuals with isolated
      holoprosencephaly (HPE) and normal chromosomes. Overall, we encountered 16 HPE
      patients (from 15 unrelated families) with ZIC2 mutations. Thus, ZIC2 mutation
      was the apparent cause of HPE in 3-4% of cases. Seven mutations were frameshifts
      that were predicted to result in loss of function, further supporting the idea
      that ZIC2 haploinsufficiency can result in HPE. One mutation, an alanine tract
      expansion which is caused by the expansion of an imperfect trinucleotide repeat,
      occurred in seven patients from six different families. In three of those
      families, the father was found to be apparently mosaic for the mutation. We
      hypothesize that this mutation can arise through errors in somatic recombination,
      an extremely unusual mutation mechanism. In addition, one mutation resulted in a
      single amino acid change and one mutation was an in-frame deletion of 12 amino
      acids. The central nervous system malformations seen in patients with ZIC2
      mutations ranged from alobar HPE (most common) to middle interhemispheric fusion
      defect (one case). Although severe facial anomalies are common in HPE, all of the
      patients with ZIC2 mutations had relatively normal faces, suggesting that ZIC2
      mutations represent a large proportion of HPE cases without facial malformation.

PMID- 11285245
TI  - Functional hemizygosity of PAFAH1B3 due to a PAFAH1B3-CLK2 fusion gene in a
      female with mental retardation, ataxia and atrophy of the brain.
AB  - We report on the molecular characterization of a translocation
      t(1;19)(q21.3;q13.2) in a female with mental retardation, ataxia and atrophy of
      the brain. Sequence analysis of the breakpoints revealed an ALU:-repeat-mediated
      mechanism of recombination that led to truncation of two genes: the kinase CLK2
      and PAFAH1B3, the gene product of which interacts with LIS1 as part of a
      heterotrimeric G protein complex PAF-AH1B. In addition, two reciprocal fusion
      genes are present. One expressed fusion gene encodes the first 136 amino acids of
      PAFAH1B3 followed by the complete CLK2 protein. Truncated PAFAH1B3 protein lost
      its potential to interact with LIS1 whereas CLK2 activity was conserved within
      the fusion protein. These data emphasize the importance of PAF-AH1B in brain
      development and functioning and demonstrate the first fusion gene apparently not
      associated with cancer.

PMID- 11285246
TI  - Deletion of a nuclease-sensitive region between the Igf2 and H19 genes leads to
      Igf2 misregulation and increased adiposity.
AB  - The insulin-like growth factor 2 gene (Igf2) is imprinted in most somatic tissues
      of the mouse with the exception of the choroid plexus and leptomeninges of the
      brain, where it is expressed from both alleles. The imprinting of Igf2 is
      dependent upon an imprinting control region (ICR) that lies 90 kb 3' of the gene
      and acts as a chromatin insulator to block enhancers that lie further 3' on the
      chromosome. Based on this model we would expect that enhancers of brain-specific
      expression of Igf2 would lie 5' of the ICR, and thus be insensitive to its
      action. Here we describe a 12 kb deletion of a region 5' of the ICR that is
      hypersensitive to nuclease digestion in chromatin. Its deletion results in a
      biallelic decrease in expression of Igf2, but not H19, in the brain, consistent
      with the proposal that it encodes a positive regulatory element. In addition, the
      deletion results in a minor relaxation of Igf2 imprinting in skeletal muscle and
      tongue. Lastly, the reduction in IGFII expression in the adult is accompanied by
      increased fat deposition and occasional obesity. Overweight animals are
      hypophagic, suggesting that IGFII affects fat metabolism rather than feeding
      behavior in adult mice.

PMID- 11285247
TI  - Single nucleotide polymorphisms in exons of the apo(a) kringles IV types 6 to 10
      domain affect Lp(a) plasma concentrations and have different patterns in Africans
      and Caucasians.
AB  - Lipoprotein(a) [Lp(a)] is a complex of apolipoprotein(a) [apo(a)] and low-density
      lipoprotein which is associated with atherothrombotic disease. Lp(a) plasma
      levels are controlled to a large extent by the apo(a) gene locus. Known
      polymorphisms in the apo(a) gene, including the kringle (K) IV-2 variable number
      of tandem repeats, explain only part of the large interindividual variability and
      do not explain the differences in Lp(a) concentrations between major human ethnic
      groups. Here we performed screening for single nucleotide polymorphisms (SNPs) in
      exons and flanking intron sequences of the apo(a) K IV types 6, 8, 9 and 10 which
      represent 1.3 kb of coding sequence in two African (Khoi San, Black South
      Africans) and one Caucasian (Tyroleans) populations and investigated whether they
      affect Lp(a) levels. Together, 768 alleles were analyzed. We identified 14 SNPs,
      including 11 non-synonymous SNPs (eight of which involved conserved residues),
      one splice site and two synonymous base changes. No sequence variants common to
      Africans and Caucasians were found. Several of the newly identified SNPs showed
      significant effects on Lp(a) plasma concentrations. The substitutions S37F in K
      IV-6 and G17R in K IV-8 were associated with Lp(a) levels significantly below
      average in Africans. In contrast, the R18W substitution in K IV-9, which occurred
      with a frequency of 8% in Khoi San, resulted in a significantly increased Lp(a)
      concentration. Together, our data suggest that several SNPs in the coding
      sequence of apo(a) affect Lp(a) levels. This indicates that many SNPs may have
      subtle effects on the gene product.

PMID- 11285248
TI  - The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate
      (HRS), associates with merlin in the "open" conformation and suppresses cell
      growth and motility.
AB  - The neurofibromatosis 2 tumor suppressor protein, merlin or schwannomin,
      functions as a negative growth regulator; however, its mechanism of action is not
      known. In an effort to determine how merlin regulates cell growth, we analyzed a
      recently identified novel merlin interactor, hepatocyte growth factor-regulated
      tyrosine kinase substrate (HRS). We demonstrate that regulated overexpression of
      HRS in rat schwannoma cells results in similar effects as overexpression of
      merlin, including growth inhibition, decreased motility and abnormalities in cell
      spreading. Previously, we showed that merlin forms an intramolecular association
      between the N- and C-termini and exists in "open" and "closed" conformations.
      Merlin interacts with HRS in the unfolded, or open, conformation. This HRS
      binding domain maps to merlin residues 453-557. Overexpression of C-terminal
      merlin has no effect on HRS function, arguing that merlin binding to HRS does not
      negatively regulate HRS growth suppressor activity. These results suggest the
      possibility that merlin and HRS may regulate cell growth in schwannoma cells
      through interacting pathways.

PMID- 11285249
TI  - Mutation of the gene encoding fibrillin-2 results in syndactyly in mice.
AB  - Fibrillins are large, cysteine-rich glycoproteins that form microfibrils and play
      a central role in elastic fibrillogenesis. Fibrillin-1 and fibrillin-2, encoded
      by FBN1 on chromosome 15q21.1 and FBN2 on chromosome 5q23-q31, are highly similar
      proteins. The finding of mutations in FBN1 and FBN2 in the autosomal dominant
      microfibrillopathies Marfan syndrome (MFS) and congenital contractural
      arachnodactyly (CCA), respectively, has highlighted their essential role in the
      development and homeostasis of elastic fibres. MFS is characterized by
      cardiovascular, skeletal and ocular abnormalities, and CCA by long, thin, flexed
      digits, crumpled ears and mild joint contractures. Although mutations arise
      throughout FBN1, those clustering within exons 24-32 are associated with the most
      severe form of MFS, so-called neonatal MFS. All the mutations described in CCA
      occur in the "neonatal region" of FBN2. Both MFS and CCA are thought to arise via
      a dominant negative mechanism. The analysis of mouse mutations has demonstrated
      that fibrillin-1 microfibrils are mainly engaged in tissue homeostasis rather
      than elastic matrix assembly. In the current investigation, we have analysed the
      classical mouse mutant shaker-with-syndactylism using a positional candidate
      approach and demonstrated that loss-of-function mutations outside the "neonatal
      region" of Fbn2 cause syndactyly in mice. These results suggest that phenotypes
      distinct from CCA may result in man as a consequence of mutations outside the
      "neonatal region" of FBN2.

PMID- 11285250
TI  - Mouse tissue culture models of unstable triplet repeats: in vitro selection for
      larger alleles, mutational expansion bias and tissue specificity, but no
      association with cell division rates.
AB  - The expansion of CAG.CTG trinucleotide repeats has been associated with an
      increasing number of human diseases. Once into the expanded disease-associated
      range, the repeats become dramatically unstable in the germline and also
      throughout the soma. Instability is expansion-biased, contributing towards the
      unusual genetics, and most likely the tissue-specificity and progressive nature
      of the symptoms. Such expansions constitute a unique form of dynamic mutation
      whose mechanism is poorly understood. It is generally assumed that repeat length
      changes arise via replication slippage, yet no direct evidence exists to support
      this hypothesis in a mammalian system. We have previously generated transgenic
      mouse models of unstable CAG.CTG repeats that reconstitute the dynamic nature of
      somatic mosaicism observed in humans. We have now used tissues from these mice to
      establish in vitro cell cultures. Monitoring of repeat stability in these cells
      has revealed the progressive accumulation of larger alleles as a result of repeat
      length changes in vitro, as confirmed by single cell cloning. We also observed
      the selection of cells carrying longer repeats during the first few passages of
      the cultures and frequent additional selective sweeps at later stages. The
      highest levels of instability were observed in cultured kidney cells, whereas the
      transgene remained relatively stable in eye cells and very stable in lung cells,
      paralleling the previous in vivo observations. No correlation between repeat
      instability and the cell proliferation rate was found, rejecting a simple
      association between length change mutations and cell division, and confirming a
      role for additional cell-type specific factors.

PMID- 11285251
TI  - "Mitotic drive" of expanded CTG repeats in myotonic dystrophy type 1 (DM1).
AB  - In myotonic dystrophy type 1 (DM1), an expanded CTG repeat shows repeat size
      instability in somatic and germ line tissues with a strong bias toward further
      expansion. To investigate the mechanism of this expansion bias, 29 DM1 and six
      normal lymphoblastoid cell lines (LBCLs) were single-cell cloned from blood cells
      of 18 DM1 patients and six normal subjects. In all 29 cell lines, the expanded
      CTG repeat alleles gradually shifted toward further expansion by "step-wise"
      mutations. Of these 29 cell lines, eight yielded a rapidly proliferating mutant
      with a gain of large repeat size that became the major allele population,
      eventually replacing the progenitor allele population. By mixing cell lines with
      different repeat expansions, we found that cells with larger CTG repeat expansion
      had a growth advantage over those with smaller expansions in culture. This growth
      advantage was attributable to increased cell proliferation mediated by Erk1,2
      activation, which is negatively regulated by p21(WAF1). This phenomenon, which we
      designated "mitotic drive" , is a novel mechanism which can explain the expansion
      bias of DM1 CTG repeat instability at the tissue level, on a basis independent of
      the DNA-based expansion models. The lifespans of the DM1 LBCLs were significantly
      shorter than normal cell lines. Thus, we propose a hypothesis that DM1 LBCLs
      drive themselves to extinction through a process related to increased
      proliferation.

PMID- 11285252
TI  - Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl
      syndrome (BBS2).
AB  - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive
      disorder with the primary clinical features of obesity, pigmented retinopathy,
      polydactyly, hypogenitalism, mental retardation and renal anomalies. Associated
      features of the disorder include diabetes mellitus, hypertension and congenital
      heart disease. There are six known BBS loci, mapping to chromosomes 2, 3, 11, 15,
      16 and 20. The BBS2 locus was initially mapped to an 18 cM interval on chromosome
      16q21 with a large inbred Bedouin kindred. Further analysis of the Bedouin
      population allowed for the fine mapping of this locus to a 2 cM region distal to
      marker D16S408. Physical mapping and sequence analysis of this region resulted in
      the identification of a number of known genes and expressed sequence tag
      clusters. Mutation screening of a novel gene (BBS2) with a wide pattern of tissue
      expression revealed homozygous mutations in two inbred pedigrees, including the
      large Bedouin kindred used to initially identify the BBS2 locus. In addition,
      mutations were found in three of 18 unrelated BBS probands from small nuclear
      families.

PMID- 11285253
TI  - Mutations in the gene encoding SLURP-1 in Mal de Meleda.
AB  - Mal de Meleda (MDM) is a rare autosomal recessive skin disorder, characterized by
      transgressive palmoplantar keratoderma (PPK), keratotic skin lesions, perioral
      erythema, brachydactyly and nail abnormalities. We report the refinement of our
      previously described interval of MDM on chromosome 8qter, and the identification
      of mutations in affected individuals in the ARS (component B) gene, encoding a
      protein named SLURP-1, for secreted Ly-6/uPAR related protein 1. This protein is
      a member of the Ly-6/uPAR superfamily, in which most members have been localized
      in a cluster on chromosome 8q24.3. The amino acid composition of SLURP-1 is
      homologous to that of toxins such as frog cytotoxin and snake venom neurotoxins
      and cardiotoxins. Three different homozygous mutations (a deletion, a nonsense
      and a splice site mutation) were detected in 19 families of Algerian and Croatian
      origin, suggesting founder effects. Moreover, one of the common haplotypes
      presenting the same mutation was shared by families from both populations.
      Secreted and receptor proteins of the Ly-6/uPAR superfamily have been implicated
      in transmembrane signal transduction, cell activation and cell adhesion. This is
      the first instance of a secreted protein being involved in a PPK.

PMID- 11285254
TI  - Conditional linkage disequilibrium analysis of a complex disease superlocus,
      IDDM1 in the HLA region, reveals the presence of independent modifying gene
      effects influencing the type 1 diabetes risk encoded by the major HLA-DQB1, -DRB1
      disease loci.
AB  - Type 1 diabetes mellitus is a common disease with a complex mode of inheritance.
      Its aetiology is underpinned by a major locus, insulin-dependent diabetes
      mellitus 1 (IDDM1) in the human leukocyte antigen (HLA) region of chromosome
      6p21, and an unknown number of loci of lesser individual effect. In linkage
      analyses IDDM1 is a single peak, but it is evident that the linkage is caused by
      allelic variation of three adjacent genes in a 75 kb region, namely the class II
      genes, HLA-DRB1, -DQA1 and -DQB1. However, even these three genes may not explain
      all of the HLA association. We investigated, in the founder population of
      Sardinia, whether non-DQ/DR polymorphic markers within a 9.452 Mb region
      encompassing the whole HLA complex further influence the disease risk, after
      taking into account linkage disequilibrium with the disease loci HLA-DQB1, -DQA1
      and -DRB1. We generalized the conditional association test, the haplotype method,
      to detect marker associations that are independent of the main DR/DQ disease
      associations. Three regions were identified as risk modifiers. These associations
      were not only independent of the polymorphic exon 2 sequences of HLA-DQB1, -DQA1
      and -DRB1, but also independent of each other. The individual contributions of
      these risk modifiers were relatively modest but their combined impact was highly
      significant. Together, alleles of single nucleotide polymorphisms at the DMB and
      DOB genes, and the microsatellite locus TNFc, identified approximately 40% of
      Sardinian DR3 haplotypes as non-predisposing. This conditional analysis approach
      can be applied to any chromosome region involved in the predisposition to complex
      traits.

PMID- 11285255
TI  - Phosphodiesterase 4D and protein kinase a type II constitute a signaling unit in
      the centrosomal area.
AB  - The mediation of cAMP effects by specific pools of protein kinase A (PKA)
      targeted to distinct subcellular domains raises the question of how inactivation
      of the cAMP signal is achieved locally and whether similar targeting of
      phosphodiesterases (PDEs) to sites of cAMP/PKA action could be observed. Here, we
      demonstrate that Sertoli cells of the testis contain an insoluble PDE4D3 isoform,
      which is shown by immunofluorescence to target to centrosomes. Staining of PDE4D
      and PKA shows co-localization of PDE4D with PKA-RIIalpha and RIIbeta in the
      centrosomal region. Co-precipitation of RII subunits and PDE4D3 from cytoskeletal
      extracts indicates a physical association of the two proteins. Distribution of
      PDE4D overlaps with that of the centrosomal PKA-anchoring protein, AKAP450, and
      AKAP450, PDE4D3, and PKA-RIIalpha co-immunoprecipitate. Finally, both PDE4D3 and
      PKA co-precipitate with a soluble fragment of AKAP450 encompassing amino acids
      1710 to 2872 when co-expressed in 293T cells. Thus, a centrosomal complex that
      includes PDE4D and PKA constitutes a novel signaling unit that may provide
      accurate spatio-temporal modulation of cAMP signals.

PMID- 11285256
TI  - The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates
      neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan
      monocyte-expressed chemoattractant receptor FPRL2.
AB  - Neutrophils express the G protein-coupled N-formyl peptide receptor (FPR) and its
      homologue FPRL1, whereas monocytes express FPR, FPRL1, and FPRL2, an orphan
      receptor sharing 83% amino acid identity with FPRL1. FPRL1 is a promiscuous
      receptor activated by serum amyloid A and by different synthetic peptides,
      including the hexapeptide Trp-Lys-Tyr-Met-Val-d-Met-NH(2) (WKYMVm). By measuring
      calcium flux in HL-60 cells transfected with FPR, FPRL1, or FPRL2, we show that
      WKYMVm activated all three receptors, whereas the l-conformer WKYMVM activated
      exclusively FPRL1 and FPRL2. The functionality of FPRL2 was further assessed by
      the ability of HL-60-FPRL2 cells to migrate toward nanomolar concentrations of
      hexapeptides. The half-maximal effective concentrations of WKYMVM for calcium
      mobilization in HL-60-FPRL1 and HL-60-FPRL2 cells were 2 and 80 nm, respectively.
      Those of WKYMVm were 75 pm and 3 nm. The tritiated peptide WK[3,5-(3)H(2)]YMVM
      bound to FPRL1 (K(D) approximately 160 nm), but not to FPR. The two conformers
      similarly inhibited binding of (125)I-labeled WKYMVm to FPRL2-expressing cells
      (IC(50) approximately 2.5-3 micrometer). Metabolic labeling with orthophosphoric
      acid revealed that FPRL1 was differentially phosphorylated upon addition of the l
      or d-conformer, indicating that it induced different conformational changes. In
      contrast to FPRL1, FPRL2 was already phosphorylated in the absence of agonist and
      not evenly distributed in the plasma membrane of unstimulated cells. However,
      both receptors were internalized upon addition of either of the two conformers.
      Taken together, the results indicate that neutrophils are activated by WKYMVM
      through FPRL1 and that FPRL2 is a chemotactic receptor transducing signals in
      myeloid cells.

PMID- 11285257
TI  - The triple threat to nascent apolipoprotein B. Evidence for multiple, distinct
      degradative pathways.
AB  - We previously showed that Omega-3 fatty acids reduce secretion of apolipoprotein
      B (apoB) from cultured hepatocytes by stimulating post-translational degradation.
      In this report, we now characterize this process, particularly in regard to the
      two known processes that degrade newly synthesized apoB, endoplasmic reticulum
      (ER)-associated degradation and re-uptake from the cell surface. First, we found
      that Omega-3-induced degradation preferentially reduces the secretion of large,
      assembled apoB-lipoprotein particles, and apoB polypeptide length is not a
      determinant. Second, based on several experimental approaches, ER-associated
      degradation is not involved. Third, re-uptake, the only process known to destroy
      fully assembled nascent lipoproteins, was clearly active in primary hepatocytes,
      but Omega-3-induced degradation of apoB continued even when re-uptake was
      blocked. Cell fractionation showed that Omega-3 fatty acids induced a striking
      loss of apoB100 from the Golgi, while sparing apoB100 in the ER, indicating a
      post-ER process. To determine the signaling involved, we used wortmannin, a
      phosphatidylinositol 3-kinase (PI3K) inhibitor, which blocked most, if not all,
      of the Omega-3 fatty acid effect. Therefore, nascent apoB is subject to ER
      associated degradation, re-uptake, and a third distinct degradative pathway that
      appears to target lipoproteins after considerable assembly and involves a post-ER
      compartment and PI3K signaling. Physiologic, pathophysiologic, and pharmacologic
      regulation of net apoB secretion may involve alterations in any of these three
      degradative steps.

PMID- 11285258
TI  - Toll-like receptor-2 mediates Treponema glycolipid and lipoteichoic acid-induced
      NF-kappaB translocation.
AB  - Recently Toll-like receptors (TLRs) have been found to be involved in cellular
      activation by microbial products, including lipopolysaccharide, lipoproteins, and
      peptidoglycan. Although for these ligands the specific transmembrane signal
      transducers TLR-4, TLR-2, or TLR-2 and -6 have now been identified, the molecular
      basis of recognition of lipoteichoic acids (LTAs) and related glycolipids has not
      been completely understood. In order to determine the role of TLRs in immune cell
      activation by these stimuli, experiments involving TLR-2-negative cell lines, TLR
      expression plasmids, macrophages from TLR-4-deficient C3H/HeJ-mice, and
      inhibitory TLR-4/MD-2 antibodies were performed. Glycolipids from Treponema
      maltophilum and Treponema brennaborense, as well as highly purified LTAs from
      Staphylococcus aureus and Bacillus subtilis exhibited TLR-2 dependence in nuclear
      factor kappaB activation and cytokine induction; however, T. brennaborense
      additionally appeared to signal via TLR-4. Fractionation of the T. brennaborense
      glycolipids by hydrophobic interaction chromatography and subsequent cell
      stimulation experiments revealed two peaks of activity, one exhibiting TLR-2-,
      and a second TLR-4-dependence. Furthermore, we show involvement of the signaling
      molecules MyD88 and NIK in cell stimulation by LTAs and glycolipids by dominant
      negative overexpression experiments. In summary, the results presented here
      indicate that TLR-2 is the main receptor for Treponema glycolipid and LTA
      mediated inflammatory response.

PMID- 11285259
TI  - alpha Arg-237 in Methylophilus methylotrophus (sp. W3A1) electron-transferring
      flavoprotein affords approximately 200-millivolt stabilization of the FAD anionic
      semiquinone and a kinetic block on full reduction to the dihydroquinone.
AB  - The midpoint reduction potentials of the FAD cofactor in wild-type Methylophilus
      methylotrophus (sp. W3A1) electron-transferring flavoprotein (ETF) and the
      alphaR237A mutant were determined by anaerobic redox titration. The FAD reduction
      potential of the oxidized-semiquinone couple in wild-type ETF (E'(1)) is +153 +/-
      2 mV, indicating exceptional stabilization of the flavin anionic semiquinone
      species. Conversion to the dihydroquinone is incomplete (E'(2) < -250 mV),
      because of the presence of both kinetic and thermodynamic blocks on full
      reduction of the FAD. A structural model of ETF (Chohan, K. K., Scrutton, N. S.,
      and Sutcliffe, M. J. (1998) Protein Pept. Lett. 5, 231-236) suggests that the
      guanidinium group of Arg-237, which is located over the si face of the flavin
      isoalloxazine ring, plays a key role in the exceptional stabilization of the
      anionic semiquinone in wild-type ETF. The major effect of exchanging alphaArg-237
      for Ala in M. methylotrophus ETF is to engineer a remarkable approximately 200-mV
      destabilization of the flavin anionic semiquinone (E'(2) = -31 +/- 2 mV, and
      E'(1) = -43 +/- 2 mV). In addition, reduction to the FAD dihydroquinone in
      alphaR237A ETF is relatively facile, indicating that the kinetic block seen in
      wild-type ETF is substantially removed in the alphaR237A ETF. Thus, kinetic (as
      well as thermodynamic) considerations are important in populating the redox forms
      of the protein-bound flavin. Additionally, we show that electron transfer from
      trimethylamine dehydrogenase to alphaR237A ETF is severely compromised, because
      of impaired assembly of the electron transfer complex.

PMID- 11285260
TI  - Maintenance of CDC42 GDP-bound state by Rho-GDI inhibits MAP kinase activation by
      the exchange factor Ras-GRF. evidence for Ras-GRF function being inhibited by
      Cdc42-GDP but unaffected by CDC42-GTP.
AB  - The function of the Ras guanine nucleotide exchange factor Ras-GRF/cdc25(Mn) is
      subject to tight regulatory processes. We have recently shown that the activation
      of the Ras/MAPK pathway by Ras-GRF is controlled by the Rho family GTPase Cdc42
      through still unknown mechanisms. Here, we report that retaining Cdc42 in its GDP
      bound state by overexpressing Rho-GDI inhibits Ras-GRF-mediated MAPK activation.
      Conversely, Ras-GRF basal and LPA- or ionomycin-stimulated activities were
      unaffected by a constitutively active GTP-bound Cdc42. Moreover, the Cdc42
      downstream effectors MLK3, ACK1, PAK1, and WASP had no detectable influence on
      Ras-GRF-mediated MAPK activation. In contrast, promoting GDP release from Cdc42
      with the Rho family GEF Dbl or with ionomycin suppressed the restraint exerted by
      Cdc42 on Ras-GRF activity. We conclude that Cdc42-GDP inhibits Ras-GRF-induced
      MAPK activation, but neither Cdc42-GTP nor the Cdc42 downstream effectors affect
      Ras-GRF performance. Interestingly, the loss of the GDP-bound state by Cdc42
      abolishes its inhibitory effects on Ras-GRF function. These results suggest that
      the Cdc42 mechanism of action may not be solely restricted to activation of
      downstream signaling cascades when GTP-loaded. Furthermore, the GDP-bound form
      may be acting as an inhibitory molecule down-modulating parallel signaling routes
      such as the Ras/MAPK pathway.

PMID- 11285261
TI  - Abrin triggers cell death by inactivating a thiol-specific antioxidant protein.
AB  - Abrin A-chain (ABRA) inhibits protein synthesis by its N-glycosidase activity as
      well as induces apoptosis, but the molecular mechanism of ABRA-induced cell death
      has been obscure. Using an ABRA mutant that lacks N-glycosidase activity as bait
      in a yeast two-hybrid system, a 30-kDa antioxidant protein-1 (AOP-1) was found to
      be an ABRA(E164Q)-interacting protein. The interaction was further confirmed in
      vitro by a glutathione S-transferase pull-down assay. The colocalization of
      endogenous AOP-1 and exogenous ABR proteins in the cell was demonstrated by
      confocal immunofluorescence. We also demonstrated that ABRA attenuates AOP-1
      antioxidant activity in a dose-dependent manner and the intracellular level of
      reactive oxygen species (ROS) increases in ABR-treated cells. Moreover, ROS
      scavengers N-acetylcysteine and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl
      delayed programmed cell death. This indicates that ROS are important mediators of
      ABR-induced apoptosis. When ectopically expressed, AOP-1 blocked the release of
      cytochrome c and prevented apoptosis in ABR-treated cells. These findings suggest
      that the binding of ABRA to AOP-1 promotes apoptosis by inhibiting the
      mitochondrial antioxidant protein AOP-1, resulting in the increase of
      intracellular ROS and the release of cytochrome c from the mitochondria to the
      cytosol, which activates caspase-9 and caspase-3.

PMID- 11285262
TI  - Crystal structure analysis of warfarin binding to human serum albumin: anatomy of
      drug site I.
AB  - Human serum albumin (HSA) is an abundant transport protein found in plasma that
      binds a wide variety of drugs in two primary binding sites (I and II) and can
      have a significant impact on their pharmacokinetics. We have determined the
      crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+)
      and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the
      protein with high affinity. The structures confirm that warfarin binds to drug
      site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular
      details of the protein-drug interaction. The two enantiomers of warfarin adopt
      very similar conformations when bound to the protein and make many of the same
      specific contacts with amino acid side chains at the binding site, thus
      accounting for the relative lack of stereospecificity of the HSA-warfarin
      interaction. The conformation of the warfarin binding pocket is significantly
      altered upon binding of fatty acids, and this can explain the observed
      enhancement of warfarin binding to HSA at low levels of fatty acid.

PMID- 11285263
TI  - Partial reconstitution of photoreceptor cGMP phosphodiesterase characteristics in
      cGMP phosphodiesterase-5.
AB  - Photoreceptor cGMP phosphodiesterases (PDE6) are uniquely qualified to serve as
      effector enzymes in the vertebrate visual transduction cascade. In the dark
      adapted photoreceptors, the activity of PDE6 is blocked via tight association
      with the inhibitory gamma-subunits (Pgamma). The Pgamma block is removed in the
      light-activated PDE6 by the visual G protein, transducin. Transducin-activated
      PDE6 exhibits an exceptionally high catalytic rate of cGMP hydrolysis ensuring
      high signal amplification. To identify the structural determinants for the
      inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we
      sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related
      cyclic GMP-specific, cGMP-binding PDE. PDE5 is insensitive to Pgamma and has a
      more than 100-fold lower k(cat) for cGMP hydrolysis. Our mutational analysis of
      chimeric PDE5/PDE6alpha' enzymes revealed that the inhibitory interaction of cone
      PDE6 catalytic subunits (PDE6alpha') with Pgamma is mediated primarily by three
      hydrophobic residues at the entry to the catalytic pocket, Met(758), Phe(777),
      and Phe(781). The maximal catalytic rate of PDE5 was enhanced by at least 10-fold
      with substitutions of PDE6alpha'-specific glycine residues for the corresponding
      PDE5 alanine residues, Ala(608) and Ala(612). The Gly residues are adjacent to
      the highly conserved metal binding motif His-Asn-X-X-His, which is essential for
      cGMP hydrolysis. Our results suggest that the unique Gly residues allow the PDE6
      metal binding site to adopt a more favorable conformation for cGMP hydrolysis.

PMID- 11285264
TI  - N-glycan structures from the major glycoproteins of pigeon egg white:
      predominance of terminal Galalpha(1)Gal.
AB  - N-Glycans from major glycoproteins of pigeon egg white (ovotransferrin,
      ovomucoid, and ovalbumins) were enzymatically released and were reductively
      aminated with 2-aminopyridine, separated, and structurally characterized by mass
      spectrometry and a three-dimensional mapping technique using three different
      columns of high performance liquid chromatography (HPLC) (Takahashi, N.,
      Nakagawa, H., Fujikawa, K., Kawamura, Y., and Tomiya, N. (1995) Anal. Biochem.
      226, 139-146). Twenty-five major N-glycan structures, all of them hitherto
      unknown, were identified as pyridylamino derivatives. Of these, 13 were neutral,
      10 were monosialyl, and 2 were disialyl oligosaccharides. All N-glycans contain
      from one to four Galalpha(1,4)Galbeta(1,4) sequences at the nonreducing terminal
      positions and are devoid of fucose residues. N-Acetylneuraminic acids were
      alpha(2,6)-linked only to beta-galactose. The HPLC profiles of the N-glycans from
      four different glycoproteins were qualitatively very similar to each other, but
      not identical in the peak distributions. Monosialyl glycans were most abundant in
      all four glycoproteins, followed by neutral glycans. Disialyl glycans were lowest
      in ovotransferrin, and highest in ovomucoid. Triantennary structures with
      bisecting GlcNAc were predominant in ovotransferrin, and tetra-antennary (with
      and without bisecting GlcNAc-containing) structures were predominant in other
      glycoproteins. Penta-antennary structures (with a sialic acid and without
      bisecting GlcNAc residue) were also found in small quantities in all four
      glycoproteins. In contrast to the chicken egg white counterparts, which contain
      mostly high mannose and hybrid types, all N-glycan structures in the major pigeon
      egg white glycoproteins are complex type.

PMID- 11285265
TI  - alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative
      voltages.
AB  - In cochlea inner hair cells (IHCs), L-type Ca(2+) channels (LTCCs) formed by
      alpha1D subunits (D-LTCCs) possess biophysical and pharmacological properties
      distinct from those of alpha1C containing C-LTCCs. We investigated to which
      extent these differences are determined by alpha1D itself by analyzing the
      biophysical and pharmacological properties of cloned human alpha1D splice
      variants in tsA-201 cells. Variant alpha1D(8A,) containing exon 8A sequence in
      repeat I, yielded alpha1D protein and L-type currents, whereas no intact protein
      and currents were observed after expression with exon 8B. In whole cell patch
      clamp recordings (charge carrier 15-20 mm Ba(2+)), alpha1D(8A) - mediated
      currents activated at more negative voltages (activation threshold, -45.7 versus 
      31.5 mV, p < 0.05) and more rapidly (tau(act) for maximal inward currents 0.8
      versus 2.3 ms; p < 0.05) than currents mediated by rabbit alpha1C. Inactivation
      during depolarizing pulses was slower than for alpha1C (current inactivation
      after 5-s depolarizations by 90 versus 99%, p < 0.05) but faster than for LTCCs
      in IHCs. The sensitivity for the dihydropyridine (DHP) L-type channel blocker
      isradipine was 8.5-fold lower than for alpha1C. Radioligand binding experiments
      revealed that this was not due to a lower affinity for the DHP binding pocket,
      suggesting that differences in the voltage-dependence of DHP block account for
      decreased sensitivity of D-LTCCs. Our experiments show that alpha1D(8A) subunits
      can form slowly inactivating LTCCs activating at more negative voltages than
      alpha1C. These properties should allow D-LTCCs to control physiological
      processes, such as diastolic depolarization in sinoatrial node cells,
      neurotransmitter release in IHCs and neuronal excitability.

PMID- 11285266
TI  - Mammalian cell morphology and endocytic membrane homeostasis require
      enzymatically active phosphoinositide 5-kinase PIKfyve.
AB  - The dual specificity mammalian enzyme PIKfyve phosphorylates in vitro position d
      5 in phosphatidylinositol (PtdIns) and PtdIns 3-P, itself or exogenous protein
      substrates. Here we have addressed the crucial questions for the identity of the
      lipid products and the role of PIKfyve enzymatic activity in mammalian cells.
      CHO, HEK293, and COS cells expressing PIKfyve(WT) at high levels and >90%
      efficiencies increased selectively the intracellular PtdIns 3,5-P(2) production
      by 30--55%. In these cell types PtdIns 5-P was undetectable. A kinase-deficient
      point mutant, PIKfyve(K1831E), transiently transfected into these or other cells
      elicited a dramatic dominant phenotype. Subsequent to a dilation of the PIKfyve
      containing vesicles, PIKfyve(K1831E)-expressing cells progressively accumulated
      multiple swollen lucent vacuoles of endosomal origin, first in the perinuclear
      cytoplasm and then toward the cell periphery. Despite their drastically altered
      morphology, the PIKfyve(K1831E)-expressing cells were viable and functionally
      active, evidenced by several criteria. This phenotype was completely reversed by
      introducing PIKfyve(WT) into the PIKfyve(K1831E)-transfected cells. Disruptions
      of the localization signal in the PIKfyve kinase-deficient mutant yielded a
      PIKfyve(K1831E Delta fyve) protein, incompetent to vacuolate cells, implying that
      an active PIKfyve enzyme at distinct late endocytic membranes is crucial for
      normal cell morphology. This was further substantiated by examining the
      vacuolation-induced potency of several pharmacological stimuli in cells
      expressing high PIKfyve(WT) levels. Together, the results indicate that PIKfyve
      enzymatic activity, possibly through the generation of PtdIns 3,5-P(2), and/or
      yet to be identified endogenous phosphoproteins, is critical for cell morphology
      and endomembrane homeostasis.

PMID- 11285267
TI  - Direct evidence for the size and conformational variability of the pyruvate
      dehydrogenase complex revealed by three-dimensional electron microscopy. The
      "breathing" core and its functional relationship to protein dynamics.
AB  - Structural studies by three-dimensional electron microscopy of the Saccharomyces
      cerevisiae truncated dihydrolipoamide acetyltransferase (tE(2)) component of the
      pyruvate dehydrogenase complex reveal an extraordinary example of protein
      dynamics. The tE(2) forms a 60-subunit core with the morphology of a pentagonal
      dodecahedron and consists of 20 cone-shaped trimers interconnected by 30 bridges.
      Frozen-hydrated and stained molecules of tE(2) in the same field vary in size
      approximately 20%. Analyses of the data show that the size distribution is bell
      shaped, and there is an approximately 40-A difference in the diameter of the
      smallest and largest structures that corresponds to approximately 14 A of
      variation in the length of the bridge between interconnected trimers. Companion
      studies of mature E(2) show that the complex of the intact subunit exhibits a
      similar size variation. The x-ray structure of Bacillus stearothermophilus tE(2)
      shows that there is an approximately 10-A gap between adjacent trimers and that
      the trimers are interconnected by the potentially flexible C-terminal ends of two
      adjacent subunits. We propose that this springlike feature is involved in a
      thermally driven expansion and contraction of the core and, since it appears to
      be a common feature in the phylogeny of pyruvate dehydrogenase complexes, protein
      dynamics is an integral component of the function of these multienzyme complexes.

PMID- 11285268
TI  - Permeation of monovalent cations through the non-capacitative arachidonate
      regulated Ca2+ channels in HEK293 cells. Comparison with endogenous store
      operated channels.
AB  - In a manner similar to voltage-gated Ca(2+) channels and Ca(2+) release-activated
      Ca(2+) (CRAC) channels, the recently identified arachidonate-regulated Ca(2+)
      (ARC) channels display a large monovalent conductance upon removal of external
      divalent cations. Using whole-cell patch-clamp recording, we have characterized
      the properties of these monovalent currents in HEK293 cells stably transfected
      with the m3 muscarinic receptor and compared them with the corresponding currents
      through the endogenous store-operated Ca(2+) (SOC) channels in the same cells.
      Although the monovalent currents seen through these two channels displayed
      certain similarities, several marked differences were also apparent, including
      the magnitude of the monovalent current/Ca(2+) current ratio, the rate and nature
      of the spontaneous decline in the currents, and the effects of external
      monovalent cation substitutions and removal of internal Mg(2+). Moreover,
      monovalent ARC currents could be activated after the complete spontaneous
      inactivation of the corresponding SOC current in the same cell. We conclude that
      the non-capacitative ARC channels share, with voltage-gated Ca(2+) channels and
      store-operated Ca(2+) channels (e.g. SOC and CRAC the general property of
      monovalent ion permeation in the nominal absence of extracellular divalent ions.
      However, the clear differences between the properties of these currents through
      ARC and SOC channels in the same cell confirm that these represent distinct
      conductances.

PMID- 11285270
TI  - Protein particles in Chlamydomonas flagella undergo a transport cycle consisting
      of four phases.
AB  - We used an improved procedure to analyze the intraflagellar transport (IFT) of
      protein particles in Chlamydomonas and found that the frequency of the particles,
      not only the velocity, changes at each end of the flagella. Thus, particles
      undergo structural remodeling at both flagellar locations. Therefore, we propose
      that the IFT consists of a cycle composed of at least four phases: phases II and
      IV, in which particles undergo anterograde and retrograde transport,
      respectively, and phases I and III, in which particles are remodeled/exchanged at
      the proximal and distal end of the flagellum, respectively. In support of our
      model, we also identified 13 distinct mutants of flagellar assembly (fla), each
      defective in one or two consecutive phases of the IFT cycle. The phase I-II
      mutant fla10-1 revealed that cytoplasmic dynein requires the function of kinesin
      II to participate in the cycle. Phase I and II mutants accumulate complex A, a
      particle component, near the basal bodies. In contrast, phase III and IV mutants
      accumulate complex B, a second particle component, in flagellar bulges. Thus, fla
      mutations affect the function of each complex at different phases of the cycle.

PMID- 11285269
TI  - Agrin-induced phosphorylation of the acetylcholine receptor regulates
      cytoskeletal anchoring and clustering.
AB  - At the developing neuromuscular junction, a motoneuron-derived factor called
      agrin signals through the muscle-specific kinase receptor to induce postsynaptic
      aggregation of the acetylcholine receptor (AChR). The agrin signaling pathway
      involves tyrosine phosphorylation of the AChR beta subunit, and we have tested
      its role in receptor localization by expressing tagged, tyrosine-minus forms of
      the beta subunit in mouse Sol8 myotubes. We find that agrin-induced
      phosphorylation of the beta subunit occurs only on cell surface AChR, and that
      AChR-containing tyrosine-minus beta subunit is targeted normally to the plasma
      membrane. Surface AChR that is tyrosine phosphorylated is less detergent
      extractable than nonphosphorylated AChR, indicating that it is preferentially
      linked to the cytoskeleton. Consistent with this, we find that agrin treatment
      reduces the detergent extractability of AChR that contains tagged wild-type beta
      subunit but not tyrosine-minus beta subunit. In addition, agrin-induced
      clustering of AChR containing tyrosine-minus beta subunit is reduced in
      comparison to wild-type receptor. Thus, we find that agrin-induced
      phosphorylation of AChR beta subunit regulates cytoskeletal anchoring and
      contributes to the clustering of the AChR, and this is likely to play an
      important role in the postsynaptic localization of the receptor at the developing
      synapse.

PMID- 11285271
TI  - Tissue transglutaminase does not contribute to the formation of mutant huntingtin
      aggregates.
AB  - The cause of Huntington's disease (HD) is a pathological expansion of the
      polyglutamine domain within the NH(2)-terminal region of huntingtin. Neuronal
      intranuclear inclusions and cytoplasmic aggregates composed of the mutant
      huntingtin within certain neuronal populations are a characteristic hallmark of
      HD. Because in vitro expanded polyglutamine repeats are glutaminyl-donor
      substrates of tissue transglutaminase (tTG), it has been hypothesized that tTG
      may contribute to the formation of these aggregates in HD. Therefore, it is of
      fundamental importance to establish whether tTG plays a significant role in the
      formation of mutant huntingtin aggregates in the cell. Human neuroblastoma SH
      SY5Y cells were stably transfected with truncated NH(2)-terminal huntingtin
      constructs containing 18 (wild type) or 82 (mutant) glutamines. In the cells
      expressing the mutant truncated huntingtin construct, numerous SDS-resistant
      aggregates were present in the cytoplasm and nucleus. Even though numerous
      aggregates were present in the mutant huntingtin-expressing cells, tTG did not
      coprecipitate with mutant truncated huntingtin. Further, tTG was totally excluded
      from the aggregates, and significantly increasing tTG expression had no effect on
      the number of aggregates or their intracellular localization (cytoplasm or
      nucleus). When a YFP-tagged mutant truncated huntingtin construct was transiently
      transfected into cells that express no detectable tTG due to stable transfection
      with a tTG antisense construct, there was extensive aggregate formation. These
      findings clearly demonstrate that tTG is not required for aggregate formation,
      and does not facilitate the process of aggregate formation. Therefore, in HD, as
      well as in other polyglutamine diseases, tTG is unlikely to play a role in the
      formation of aggregates.

PMID- 11285272
TI  - TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are
      required for maintaining articular cartilage.
AB  - Endochondral ossification begins from the condensation and differentiation of
      mesenchymal cells into cartilage. The cartilage then goes through a program of
      cell proliferation, hypertrophic differentiation, calcification, apoptosis, and
      eventually is replaced by bone. Unlike most cartilage, articular cartilage is
      arrested before terminal hypertrophic differentiation. In this study, we showed
      that TGF-beta/Smad3 signals inhibit terminal hypertrophic differentiation of
      chondrocyte and are essential for maintaining articular cartilage. Mutant mice
      homozygous for a targeted disruption of Smad3 exon 8 (Smad3(ex8/ex8)) developed
      degenerative joint disease resembling human osteoarthritis, as characterized by
      progressive loss of articular cartilage, formation of large osteophytes,
      decreased production of proteoglycans, and abnormally increased number of type X
      collagen-expressing chondrocytes in synovial joints. Enhanced terminal
      differentiation of epiphyseal growth plate chondrocytes was also observed in
      mutant mice shortly after weaning. In an in vitro embryonic metatarsal rudiment
      culture system, we found that TGF-beta1 significantly inhibits chondrocyte
      differentiation of wild-type metatarsal rudiments. However, this inhibition is
      diminished in metatarsal bones isolated from Smad3(ex8/ex8) mice. These data
      suggest that TGF-beta/Smad3 signals are essential for repressing articular
      chondrocyte differentiation. Without these inhibition signals, chondrocytes break
      quiescent state and undergo abnormal terminal differentiation, ultimately leading
      to osteoarthritis.

PMID- 11285274
TI  - The Vfl1 Protein in Chlamydomonas localizes in a rotationally asymmetric pattern
      at the distal ends of the basal bodies.
AB  - In the unicellular alga Chlamydomonas, two anterior flagella are positioned with
      180 degrees rotational symmetry, such that the flagella beat with the effective
      strokes in opposite directions (Hoops, H.J., and G.B. Witman. 1983. J. Cell Biol.
      97:902-908). The vfl1 mutation results in variable numbers and positioning of
      flagella and basal bodies (Adams, G.M.W., R.L. Wright, and J.W. Jarvik. 1985. J.
      Cell Biol. 100:955-964). Using a tagged allele, we cloned the VFL1 gene that
      encodes a protein of 128 kD with five leucine-rich repeat sequences near the
      NH(2) terminus and a large alpha-helical-coiled coil domain at the COOH terminus.
      An epitope-tagged gene construct rescued the mutant phenotype and expressed a
      tagged protein (Vfl1p) that copurified with basal body flagellar apparatuses.
      Immunofluorescence experiments showed that Vfl1p localized with basal bodies and
      probasal bodies. Immunogold labeling localized Vfl1p inside the lumen of the
      basal body at the distal end. Distribution of gold particles was rotationally
      asymmetric, with most particles located near the doublet microtubules that face
      the opposite basal body. The mutant phenotype, together with the localization
      results, suggest that Vfl1p plays a role in establishing the correct rotational
      orientation of basal bodies. Vfl1p is the first reported molecular marker of the
      rotational asymmetry inherent to basal bodies.

PMID- 11285273
TI  - A role for actin, Cdc1p, and Myo2p in the inheritance of late Golgi elements in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, Golgi elements are present in the bud very early in
      the cell cycle. We have analyzed this Golgi inheritance process using
      fluorescence microscopy and genetics. In rapidly growing cells, late Golgi
      elements show an actin-dependent concentration at sites of polarized growth. Late
      Golgi elements are apparently transported into the bud along actin cables and are
      also retained in the bud by a mechanism that may involve actin. A visual screen
      for mutants defective in the inheritance of late Golgi elements yielded multiple
      alleles of CDC1. Mutations in CDC1 severely depolarize the actin cytoskeleton,
      and these mutations prevent late Golgi elements from being retained in the bud.
      The efficient localization of late Golgi elements to the bud requires the type V
      myosin Myo2p, further suggesting that actin plays a role in Golgi inheritance.
      Surprisingly, early and late Golgi elements are inherited by different pathways,
      with early Golgi elements localizing to the bud in a Cdc1p- and Myo2p-independent
      manner. We propose that early Golgi elements arise from ER membranes that are
      present in the bud. These two pathways of Golgi inheritance in S. cerevisiae
      resemble Golgi inheritance pathways in vertebrate cells.

PMID- 11285275
TI  - Actin depolymerizing factor stabilizes an existing state of F-actin and can
      change the tilt of F-actin subunits.
AB  - Proteins in the actin depolymerizing factor (ADF)/cofilin family are essential
      for rapid F-actin turnover, and most depolymerize actin in a pH-dependent manner.
      Complexes of human and plant ADF with F-actin at different pH were examined using
      electron microscopy and a novel method of image analysis for helical filaments.
      Although ADF changes the mean twist of actin, we show that it does this by
      stabilizing a preexisting F-actin angular conformation. In addition, ADF induces
      a large ( approximately 12 degrees ) tilt of actin subunits at high pH where
      filaments are readily disrupted. A second ADF molecule binds to a site on the
      opposite side of F-actin from that of the previously described ADF binding site,
      and this second site is only largely occupied at high pH. All of these states
      display a high degree of cooperativity that appears to be an integral part of F
      actin.

PMID- 11285277
TI  - Centromeres are specialized replication domains in heterochromatin.
AB  - The properties that define centromeres in complex eukaryotes are poorly
      understood because the underlying DNA is normally repetitive and
      indistinguishable from surrounding noncentromeric sequences. However, centromeric
      chromatin contains variant H3-like histones that may specify centromeric regions.
      Nucleosomes are normally assembled during DNA replication; therefore, we examined
      replication and chromatin assembly at centromeres in Drosophila cells. DNA in
      pericentric heterochromatin replicates late in S phase, and so centromeres are
      also thought to replicate late. In contrast to expectation, we show that
      centromeres replicate as isolated domains early in S phase. These domains do not
      appear to assemble conventional H3-containing nucleosomes, and deposition of the
      Cid centromeric H3-like variant proceeds by a replication-independent pathway. We
      suggest that late-replicating pericentric heterochromatin helps to maintain
      embedded centromeres by blocking conventional nucleosome assembly early in S
      phase, thereby allowing the deposition of centromeric histones.

PMID- 11285276
TI  - Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative
      form in chondrocytes.
AB  - During skeletogenesis, cartilage develops to either permanent cartilage that
      persists through life or transient cartilage that is eventually replaced by bone.
      However, the mechanism by which cartilage phenotype is specified remains
      unclarified. Core binding factor alpha1 (Cbfa1) is an essential transcription
      factor for osteoblast differentiation and bone formation and has the ability to
      stimulate chondrocyte maturation in vitro. To understand the roles of Cbfa1 in
      chondrocytes during skeletal development, we generated transgenic mice that
      overexpress Cbfa1 or a dominant negative (DN)-Cbfa1 in chondrocytes under the
      control of a type II collagen promoter/enhancer. Both types of transgenic mice
      displayed dwarfism and skeletal malformations, which, however, resulted from
      opposite cellular phenotypes. Cbfa1 overexpression caused acceleration of
      endochondral ossification due to precocious chondrocyte maturation, whereas
      overexpression of DN-Cbfa1 suppressed maturation and delayed endochondral
      ossification. In addition, Cbfa1 transgenic mice failed to form most of their
      joints and permanent cartilage entered the endochondral pathway, whereas most
      chondrocytes in DN-Cbfa1 transgenic mice retained a marker for permanent
      cartilage. These data show that temporally and spatially regulated expression of
      Cbfa1 in chondrocytes is required for skeletogenesis, including formation of
      joints, permanent cartilages, and endochondral bones.

PMID- 11285278
TI  - FtsZ ring formation at the chloroplast division site in plants.
AB  - Among the events that accompanied the evolution of chloroplasts from their
      endosymbiotic ancestors was the host cell recruitment of the prokaryotic cell
      division protein FtsZ to function in chloroplast division. FtsZ, a structural
      homologue of tubulin, mediates cell division in bacteria by assembling into a
      ring at the midcell division site. In higher plants, two nuclear-encoded forms of
      FtsZ, FtsZ1 and FtsZ2, play essential and functionally distinct roles in
      chloroplast division, but whether this involves ring formation at the division
      site has not been determined previously. Using immunofluorescence microscopy and
      expression of green fluorescent protein fusion proteins in Arabidopsis thaliana,
      we demonstrate here that FtsZ1 and FtsZ2 localize to coaligned rings at the
      chloroplast midpoint. Antibodies specific for recognition of FtsZ1 or FtsZ2
      proteins in Arabidopsis also recognize related polypeptides and detect midplastid
      rings in pea and tobacco, suggesting that midplastid ring formation by FtsZ1 and
      FtsZ2 is universal among flowering plants. Perturbation in the level of either
      protein in transgenic plants is accompanied by plastid division defects and
      assembly of FtsZ1 and FtsZ2 into filaments and filament networks not observed in
      wild-type, suggesting that previously described FtsZ-containing cytoskeletal-like
      networks in chloroplasts may be artifacts of FtsZ overexpression.

PMID- 11285279
TI  - Cyclin A is destroyed in prometaphase and can delay chromosome alignment and
      anaphase.
AB  - Mitosis is controlled by the specific and timely degradation of key regulatory
      proteins, notably the mitotic cyclins that bind and activate the cyclin-dependent
      kinases (Cdks). In animal cells, cyclin A is always degraded before cyclin B, but
      the exact timing and the mechanism underlying this are not known. Here we use
      live cell imaging to show that cyclin A begins to be degraded just after nuclear
      envelope breakdown. This degradation requires the 26S proteasome, but is not
      affected by the spindle checkpoint. Neither deletion of its destruction box nor
      disrupting Cdk binding prevents cyclin A proteolysis, but Cdk binding is
      necessary for degradation at the correct time. We also show that increasing the
      levels of cyclin A delays chromosome alignment and sister chromatid segregation.
      This delay depends on the proteolysis of cyclin A and is not caused by a lag in
      the bipolar attachment of chromosomes to the mitotic spindle, nor is it mediated
      via the spindle checkpoint. Thus, proteolysis that is not under the control of
      the spindle checkpoint is required for chromosome alignment and anaphase.

PMID- 11285280
TI  - Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A
      starts at the beginning of mitosis and is not subject to the spindle assembly
      checkpoint.
AB  - Cyclin A is a stable protein in S and G2 phases, but is destabilized when cells
      enter mitosis and is almost completely degraded before the metaphase to anaphase
      transition. Microinjection of antibodies against subunits of the anaphase
      promoting complex/cyclosome (APC/C) or against human Cdc20 (fizzy) arrested cells
      at metaphase and stabilized both cyclins A and B1. Cyclin A was efficiently
      polyubiquitylated by Cdc20 or Cdh1-activated APC/C in vitro, but in contrast to
      cyclin B1, the proteolysis of cyclin A was not delayed by the spindle assembly
      checkpoint. The degradation of cyclin B1 was accelerated by inhibition of the
      spindle assembly checkpoint. These data suggest that the APC/C is activated as
      cells enter mitosis and immediately targets cyclin A for degradation, whereas the
      spindle assembly checkpoint delays the degradation of cyclin B1 until the
      metaphase to anaphase transition. The "destruction box" (D-box) of cyclin A is 10
      20 residues longer than that of cyclin B. Overexpression of wild-type cyclin A
      delayed the metaphase to anaphase transition, whereas expression of cyclin A
      mutants lacking a D-box arrested cells in anaphase.

PMID- 11285281
TI  - Regulation of Op18 during spindle assembly in Xenopus egg extracts.
AB  - Oncoprotein 18 (Op18) is a microtubule-destabilizing protein that is negatively
      regulated by phosphorylation. To evaluate the role of the three Op18
      phosphorylation sites in Xenopus (Ser 16, 25, and 39), we added wild-type Op18, a
      nonphosphorylatable triple Ser to Ala mutant (Op18-AAA), and to mimic
      phosphorylation, a triple Ser to Glu mutant (Op18-EEE) to egg extracts and
      monitored spindle assembly. Op18-AAA dramatically decreased microtubule length
      and density, while Op18-EEE did not significantly affect spindle microtubules.
      Affinity chromatography with these proteins revealed that the microtubule
      destabilizing activity correlated with the ability of Op18 to bind tubulin. Since
      hyperphosphorylation of Op18 is observed upon addition of mitotic chromatin to
      extracts, we reasoned that chromatin-associated proteins might play a role in
      Op18 regulation. We have performed a preliminary characterization of the
      chromatin proteins recruited to DNA beads, and identified the Xenopus polo-like
      kinase Plx1 as a chromatin-associated kinase that regulates Op18 phosphorylation.
      Depletion of Plx1 inhibits chromatin-induced Op18 hyperphosphorylation and
      spindle assembly in extracts. Therefore, Plx1 may promote microtubule
      stabilization and spindle assembly by inhibiting Op18.

PMID- 11285282
TI  - The surveillance mechanism of the spindle position checkpoint in yeast.
AB  - The spindle position checkpoint in Saccharomyces cerevisiae delays mitotic exit
      until the spindle has moved into the mother-bud neck, ensuring that each daughter
      cell inherits a nucleus. The small G protein Tem1p is critical in promoting
      mitotic exit and is concentrated at the spindle pole destined for the bud. The
      presumed nucleotide exchange factor for Tem1p, Lte1p, is concentrated in the bud.
      These findings suggested the hypothesis that movement of the spindle pole through
      the neck allows Tem1p to interact with Lte1p, promoting GTP loading of Tem1p and
      mitotic exit. However, we report that deletion of LTE1 had little effect on the
      timing of mitotic exit. We also examined several mutants in which some cells
      inappropriately exit mitosis even though the spindle is within the mother. In
      some of these cells, the spindle pole body did not interact with the bud or the
      neck before mitotic exit. Thus, some alternative mechanism must exist to
      coordinate mitotic exit with spindle position. In both wild-type and mutant
      cells, mitotic exit was preceded by loss of cytoplasmic microtubules from the
      neck. Thus, the spindle position checkpoint may monitor such interactions.

PMID- 11285283
TI  - Nucleolar components involved in ribosome biogenesis cycle between the nucleolus
      and nucleoplasm in interphase cells.
AB  - We examined the mobilities of nucleolar components that act at various steps of
      the ribosome biogenesis pathway. Fluorescence recovery after photobleaching
      (FRAP) and fluorescence loss in photobleaching (FLIP) analyses demonstrate that
      factors involved in rRNA transcription (upstream-binding factor [UBF]),
      processing (nucleolin, fibrillarin, and RNase MRP subunits, Rpp29), and ribosome
      assembly (B23) exchange rapidly between the nucleoplasm and nucleolus. In
      contrast, the mobilities of ribosomal subunit proteins (S5, L9) are much slower.
      Selective inhibition of RNA polymerase I transcription does not prevent the
      exchanges but influences the rates of exchange differentially for different
      nucleolar components. These findings suggest that the rapid exchange of nucleolar
      components between the nucleolus and nucleoplasm may represent a new level of
      regulation for rRNA synthesis. The different dynamic properties of proteins
      involved in different steps of ribosome biogenesis imply that the nucleolar
      association of these proteins is due to their specific functional roles rather
      than simply their specific nucleolar-targeting events.

PMID- 11285284
TI  - Restriction of secretory granule motion near the plasma membrane of chromaffin
      cells.
AB  - We used total internal reflection fluorescence microscopy to study quantitatively
      the motion and distribution of secretory granules near the plasma membrane (PM)
      of living bovine chromaffin cells. Within the approximately 300-nm region
      measurably illuminated by the evanescent field resulting from total internal
      reflection, granules are preferentially concentrated close to the PM. Granule
      motion normal to the substrate (the z direction) is much slower than would be
      expected from free Brownian motion, is strongly restricted over tens of nanometer
      distances, and tends to reverse directions within 0.5 s. The z-direction
      diffusion coefficients of granules decrease continuously by two orders of
      magnitude within less than a granule diameter of the PM as granules approach the
      PM. These analyses suggest that a system of tethers or a heterogeneous matrix
      severely limits granule motion in the immediate vicinity of the PM. Transient
      expression of the light chains of tetanus toxin and botulinum toxin A did not
      disrupt the restricted motion of granules near the PM, indicating that SNARE
      proteins SNAP-25 and VAMP are not necessary for the decreased mobility. However,
      the lack of functional SNAREs on the plasma or granule membranes in such cells
      reduces the time that some granules spend immediately adjacent to the PM.

PMID- 11285287
TI  - The inhibitor of apoptosis protein-binding domain of Smac is not essential for
      its proapoptotic activity.
AB  - Smac/DIABLO, a recently identified inhibitor of apoptosis protein (IAP)-binding
      protein, is released from the mitochondria during apoptosis and reportedly
      potentiates apoptosis by relieving the inhibition of IAPs on caspases. We now
      describe the molecular characterization of Smac beta, an alternatively spliced
      form of Smac, which lacks the mitochondrial-targeting sequence found in Smac and
      has a cortical distribution in both human embryonic kidney 293 and breast
      epithelial tumor MCF-7 cells. Smac beta, which binds IAPs in vitro, does not bind
      IAPs in intact cells due to cellular processing and removal of its NH(2)-terminal
      IAP-binding domain. Despite its inability to interact with IAPs in cells,
      processed Smac beta is proapoptotic, as demonstrated by its ability to potentiate
      apoptosis induced by both death receptor and chemical stimuli. Furthermore,
      expression of a NH(2)-terminally truncated Smac mutant (Delta75), which lacks the
      entire IAP-interacting domain, potentiates apoptosis to the same extent as Smac
      and Smac beta. Our data support the hypothesis that the main proapoptotic
      function of Smac and Smac beta is due to a mechanism other than IAP binding.

PMID- 11285286
TI  - Role of diacylglycerol kinase alpha in the attenuation of receptor signaling.
AB  - Diacylglycerol kinase (DGK) is suggested to attenuate diacylglycerol-induced cell
      responses through the phosphorylation of this second messenger to phosphatidic
      acid. Here, we show that DGKalpha, an isoform highly expressed in T lymphocytes,
      translocates from cytosol to the plasma membrane in response to two different
      receptors known to elicit T cell activation responses: an ectopically expressed
      muscarinic type I receptor and the endogenous T cell receptor. Translocation in
      response to receptor stimulation is rapid, transient, and requires calcium and
      tyrosine kinase activation. DGKalpha-mediated phosphatidic acid generation allows
      dissociation of the enzyme from the plasma membrane and return to the cytosol, as
      demonstrated using a pharmacological inhibitor and a catalytically inactive
      version of the enzyme. The NH(2)-terminal domain of the protein is shown to be
      responsible for receptor-induced translocation and phosphatidic acid-mediated
      membrane dissociation. After examining induction of the T cell activation marker
      CD69 in cells expressing a constitutively active form of the enzyme, we present
      evidence of the negative regulation that DGKalpha exerts on diacylglycerol
      derived cell responses. This study is the first to describe DGKalpha as an
      integral component of the signaling cascades that link plasma membrane receptors
      to nuclear responses.

PMID- 11285285
TI  - Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that
      binds to the first PDZ domain of EBP50 and E3KARP.
AB  - The cortical scaffolding proteins EBP50 (ERM-binding phosphoprotein-50) and
      E3KARP (NHE3 kinase A regulatory protein) contain two PDZ (PSD-95/DlgA/ZO-1-like)
      domains followed by a COOH-terminal sequence that binds to active ERM family
      members. Using affinity chromatography, we identified polypeptides from placental
      microvilli that bind the PDZ domains of EBP50. Among these are 64- and/or 65-kD
      differentially phosphorylated polypeptides that bind preferentially to the first
      PDZ domain of EBP50, as well as to E3KARP, and that we call EPI64 (EBP50-PDZ
      interactor of 64 kD). The gene for human EPI64 lies on chromosome 22 where nine
      exons specify a protein of 508 residues that contains a Tre/Bub2/Cdc16 (TBC)/rab
      GTPase-activating protein (GAP) domain. EPI64 terminates in DTYL, which is
      necessary for binding to the PDZ domains of EBP50, as a mutant ending in DTYLA no
      longer interacts. EPI64 colocalizes with EBP50 and ezrin in syncytiotrophoblast
      and cultured cell microvilli, and this localization in cultured cells is
      abolished by introduction of the DTYLA mutation. In addition to EPI64,
      immobilized EBP50 PDZ domains retain several polypeptides from placental
      microvilli, including an isoform of nadrin, a rhoGAP domain-containing protein
      implicated in regulating vesicular transport. Nadrin binds EBP50 directly,
      probably through its COOH-terminal STAL sequence. Thus, EBP50 appears to bind
      membrane proteins as well as factors potentially involved in regulating membrane
      traffic.

PMID- 11285288
TI  - Actin bound to the heterogeneous nuclear ribonucleoprotein hrp36 is associated
      with Balbiani ring mRNA from the gene to polysomes.
AB  - In the salivary glands of the dipteran Chironomus tentans, a specific messenger
      ribonucleoprotein (mRNP) particle, the Balbiani ring (BR) granule, can be
      visualized during its assembly on the gene and during its nucleocytoplasmic
      transport. We now show with immunoelectron microscopy that actin becomes
      associated with the BR particle concomitantly with transcription and is present
      in the particle in the nucleoplasm. DNase I affinity chromatography experiments
      with extracts from tissue culture cells indicate that both nuclear and
      cytoplasmic actin are bound to the heterogeneous RNP (hnRNP) protein hrp36, but
      not to the hnRNP proteins hrp23 and hrp45. The interaction is likely to be direct
      as purified actin binds to recombinant hrp36 in vitro. Furthermore, it is
      demonstrated by cross linking that nuclear as well as cytoplasmic actin are bound
      to hrp36 in vivo. It is known that hrp36 is added cotranscriptionally along the
      BR mRNA molecule and accompanies the RNA through the nuclear pores and into
      polysomes. We conclude that actin is likely to be bound to the BR transcript via
      hrp36 during the transfer of the mRNA from the gene all the way into polysomes.

PMID- 11285289
TI  - Centrosomes enhance the fidelity of cytokinesis in vertebrates and are required
      for cell cycle progression.
AB  - When centrosomes are destroyed during prophase by laser microsurgery, vertebrate
      somatic cells form bipolar acentrosomal mitotic spindles (Khodjakov, A., R.W.
      Cole, B.R. Oakley, and C.L. Rieder. 2000. Curr. Biol. 10:59-67), but the fate of
      these cells is unknown. Here, we show that, although these cells lack the radial
      arrays of astral microtubules normally associated with each spindle pole, they
      undergo a normal anaphase and usually produce two acentrosomal daughter cells.
      Relative to controls, however, these cells exhibit a significantly higher (30
      50%) failure rate in cytokinesis. This failure correlates with the inability of
      the spindle to properly reposition itself as the cell changes shape. Also, we
      destroyed just one centrosome during metaphase and followed the fate of the
      resultant acentrosomal and centrosomal daughter cells. Within 72 h, 100% of the
      centrosome-containing cells had either entered DNA synthesis or divided. By
      contrast, during this period, none of the acentrosomal cells had entered S phase.
      These data reveal that the primary role of the centrosome in somatic cells is not
      to form the spindle but instead to ensure cytokinesis and subsequent cell cycle
      progression.

PMID- 11285290
TI  - Helicobacter pylori genetic diversity and risk of human disease.

PMID- 11285291
TI  - Diverse virulence traits underlying different clinical outcomes of Salmonella
      infection.
AB  - Salmonella strains have evolved to infect a wide variety of reptiles, birds, and
      mammals resulting in many different syndromes ranging from colonization and
      chronic carriage to acute fatal disease. Adaptation to a large number of
      different evolutionary niches has undoubtedly driven the high degree of
      phenotypic and genotypic diversity in Salmonella strains. Differences in LPS and
      flagellar structure generate the antigenic variation that is reflected in the
      more than 2,000 known serotypes. Moreover, variations of LPS structure affect the
      virulence of the strain. The differential expression of various fimbriae by
      Salmonella is likely to be due to the wide variety of mucosal surfaces that are
      encountered by various strains, and the host immune response may select for a
      different expression pattern. As with these surface structures, a variety of
      other important virulence determinants show a variable distribution in Salmonella
      strains and also serve to delineate the divergence of the Salmonella lineage from
      E. coli. The acquisition of the SPI-1 region may have represented the defining
      genetic event in the separation of the Salmonella and E. coli lineages. The SPI-1
      cell invasion function allowed Salmonella to establish a separate niche in
      epithelial cells. The mgtC locus on SPI-3 is also present in all lineages and
      facilitates the adaptation of the bacteria to the low Mg2+, low pH environment of
      the endosome that results from SPI-1-mediated invasion. Subsequent acquisition of
      SPI-2 allowed Salmonella to manipulate the sorting of the endosome or phagosome,
      altering the intracellular environment and facilitating bacterial growth within
      infected cells. The ability to disseminate from the bowel and establish
      extraintestinal niches is promoted by the spv locus. Since Salmonella
      proliferates within macrophages and must avoid phagocytosis by neutrophils to
      establish a systemic infection, the spv genes appear to promote the macrophage
      phase of the disease process. Here the polymorphism of the spv locus is clearly
      demonstrated, since the serovars that cause most cases of nontyphoid bacteremia
      contain the spv genes. The absence of the spv genes from S. typhi is particularly
      puzzling and is a strong indication that the pathogenesis of typhoid fever is
      fundamentally different from that of bacteremia due to nontyphoid Salmonella.
      There is currently no genetic explanation for the phenotype of host adaptation or
      for the finding that only a few serovars cause the majority of human infections.
      Based on recent findings that multiple individual virulence genes have a variable
      distribution in Salmonella, it is unlikely that a single locus will be found to
      be responsible for these complex biological traits. Instead, a complicated
      combination of genes are likely to contribute to the overall virulence phenotype.

PMID- 11285292
TI  - Regulation of interactions between cells and extracellular matrix: a command
      performance on several stages.

PMID- 11285293
TI  - The de-adhesive activity of matricellular proteins: is intermediate cell adhesion
      an adaptive state?
AB  - The process of cellular de-adhesion is potentially important for the ability of a
      cell to participate in morphogenesis and to respond to injurious stimuli.
      Cellular de-adhesion is induced by the highly regulated matricellular proteins
      TSP1 and 2, tenascin-C, and SPARC. These proteins induce a rapid transition to an
      intermediate state of adhesiveness characterized by loss of actin-containing
      stress fibers and restructuring of the focal adhesion plaque that includes loss
      of vinculin and alpha-actinin, but not of talin or integrin. This process
      involves intracellular signaling mediators, which are engaged in response to
      matrix protein-receptor interactions. Each of these proteins employs different
      receptors and signaling pathways to achieve this common morphologic endpoint.
      What is the function of this intermediate adhesive state and what is the
      physiologic significance of this action of the matricellular proteins? Given that
      matricellular proteins are expressed in response to injury and during
      development, one can speculate that the intermediate adhesive state is an
      adaptive condition that facilitates expression of specific genes that are
      involved in repair and adaptation. Since cell shape is maintained in weakly
      adherent cells, this state might induce survival signals to prevent apoptosis due
      to loss of strong cell adhesion, but yet allow for cell locomotion. The three
      matricellular proteins considered here might each preferentially facilitate one
      or more aspects of this adaptive response rather than all of these equally.
      Currently, we have only preliminary data to support the specific ideas proposed
      in this article. It will be interesting in the next several years to continue to
      elucidate the biological roles of the intermediate adhesive state induced by
      these matricellular proteins. and focal adhesions in a cell that nevertheless
      maintains a spread, extended morphology and integrin clustering. TSP1, tenascin
      C, and SPARC induce the intermediate adhesive state, as shown by the red arrows.
      The significance of each adhesive state for cell behavior is indicated beneath
      the cells. The weak adhesive state would be consistent with cells undergoing
      apoptosis during remodeling or those undergoing cytokinesis. The strong adhesive
      state is characteristic of a differentiated, quiescent cell, whereas cells in the
      intermediate adhesive state would include those involved in responding to injury
      during wound healing or in tissue remodeling during morphogenesis.

PMID- 11285294
TI  - Chemokines: the times they are a-changin'.

PMID- 11285295
TI  - Imprints of disease at GNAS1.

PMID- 11285296
TI  - DR, DQ, and you: MHC alleles and autoimmunity.

PMID- 11285297
TI  - Routes to allograft survival.

PMID- 11285298
TI  - Transition metals redox: reviving an old plot for diabetic vascular disease.

PMID- 11285299
TI  - Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in
      the murine bone marrow by 17 beta-estradiol.
AB  - In agreement with evidence that estrogens slow the rate of bone remodeling by
      suppressing the production of both osteoclasts and osteoblasts, loss of estrogens
      leads to an increase in the number of osteoclast as well as early osteoblast
      progenitors (CFU-osteoblasts; CFU-OBs) in the murine bone marrow. Here we show
      that CFU-OBs are early transit-amplifying progenitors, i.e., dividing cells
      capable of limited self-renewal, and that 17 beta-estradiol acts in vivo and in
      vitro to attenuate their self-renewal by approximately 50%. Consistent with a
      direct receptor-mediated action of estrogens on early mesenchymal cell
      progenitors, anti-estrogen receptor-alpha (anti-ER alpha) Ab's stain a small
      number of marrow cells that exhibit characteristics of primitive undifferentiated
      cells, including a high nucleus/cytoplasm ratio and lack of lineage-specific
      biochemical markers; the effect of 17 beta-estradiol on CFU-OB self-renewal is
      absent in mice lacking ER alpha. Because both osteoblasts and the
      stromal/osteoblastic cells that are required for osteoclast development are
      derived from CFU-OBs, suppression of the self-renewal of this common progenitor
      may represent a key mechanism of the anti-remodeling effects of estrogens.

PMID- 11285300
TI  - A novel mouse model of lipotoxic cardiomyopathy.
AB  - Inherited and acquired cardiomyopathies are associated with marked intracellular
      lipid accumulation in the heart. To test the hypothesis that mismatch between
      myocardial fatty acid uptake and utilization leads to the accumulation of
      cardiotoxic lipid species, and to establish a mouse model of metabolic
      cardiomyopathy, we generated transgenic mouse lines that overexpress long-chain
      acyl-CoA synthetase in the heart (MHC-ACS). This protein plays an important role
      in vectorial fatty acid transport across the plasma membrane. MHC-ACS mice
      demonstrate cardiac-restricted expression of the transgene and marked cardiac
      myocyte triglyceride accumulation. Lipid accumulation is associated with initial
      cardiac hypertrophy, followed by the development of left-ventricular dysfunction
      and premature death. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling staining and cytochrome c release in transgenic hearts suggest that
      cardiac myocyte death occurs, in part, by lipid-induced programmed cell death.
      Taken together, our data demonstrate that fatty acid uptake/utilization mismatch
      in the heart leads to accumulation of lipid species toxic to cardiac myocytes.
      This novel mouse model will provide insight into the role of perturbations in
      myocardial lipid metabolism in the pathogenesis of inherited and acquired forms
      of heart failure.

PMID- 11285301
TI  - CArG elements control smooth muscle subtype-specific expression of smooth muscle
      myosin in vivo.
AB  - Expression of smooth muscle myosin heavy chain (SM-MHC) is tightly controlled
      depending on the differentiated state of smooth muscle cells (SMCs). To better
      understand the mechanisms that regulate transcription of the SM-MHC gene in vivo,
      we tested the function of several conserved CArG elements contained within the 
      4200 to +11,600 region of this gene that we had previously shown to drive SMC
      specific expression in transgenic mice. CArG1 in the 5'-flanking sequence was
      required for all SMCs, while CArG2 and a novel intronic CArG element were
      differentially required in SMC subtypes. Of particular note, mutation of the
      intronic CArG selectively abolished expression in large arteries. A promoter
      construct containing three repeats of a conserved 227-bp intronic CArG-containing
      region was sufficient to direct transcription in vascular SMCs in transgenic
      mice, although this construct was also expressed in skeletal and cardiac muscle.
      These results support a model in which transcriptional regulation of SM-MHC is
      controlled by multiple positive and negative modular control regions that differ
      between SMCs and non-SMCs and among SMC subtypes. We also demonstrated that the
      CArG elements of the endogenous SM-MHC gene were bound by SRF in chromatin.

PMID- 11285302
TI  - Human thymus contains IFN-alpha-producing CD11c(-), myeloid CD11c(+), and mature
      interdigitating dendritic cells.
AB  - Three distinct dendritic cell (DC) subsets capable of stimulating allogeneic
      naive T cells were isolated from human thymus. The most abundant subset was
      represented by plasmacytoid DCs (pDCs), which secreted high amounts of IFN-alpha
      upon stimulation with inactivated influenza virus and thus likely correspond to
      the recently identified peripheral blood natural IFN-alpha/beta-producing cells
      (IPCs). Like those latter cells, thymic pDCs had distinctive phenotypic features
      (i.e., Lin(-), HLA-DR(int), IL-3R alpha(hi), CD45RA(hi), CD11c(-), CD13(-), and
      CD33(lo)) and developed into mature DCs upon culture in IL-3 and CD40L. Of the
      two other DC subsets, one displayed a phenotype of immature myeloid DCs (imDCs)
      (HLA-DR(int), CD11c(+), CD13(+), CD33(+)), and the other represented HLA-DR(hi)
      CD11c(+) mature DCs (mDCs). Since they also expressed DC-LAMP, these mDCs appear
      to correspond to interdigitating dendritic cells (IDCs). Thymic pDCs, but not
      myeloid imDCs, strongly expressed lymphoid-specific transcripts such as pre-T
      alpha, lambda-like, and Spi-B, thereby suggesting a possible lymphoid origin. The
      detection of Spi-B mRNA, not only upon in vitro maturation of pDCs, but also in
      freshly purified IDCs, suggests that in vivo pDCs may differentiate into IDCs.

PMID- 11285303
TI  - Resistance to Lyme disease in decorin-deficient mice.
AB  - Microbial adhesion to the host tissue represents an early, critical step in the
      pathogenesis of most infectious diseases. BORRELIA: burgdorferi, the causative
      agent of Lyme disease (LD), expresses two surface-exposed decorin-binding
      adhesins, DbpA and DbpB. A decorin-deficient (Dcn(-/-)) mouse was recently
      developed and found to have a relatively mild phenotype. We have now examined the
      process of experimental LD in Dcn(-/-) mice using both needle inoculation and
      tick transmission of spirochetes. When exposed to low doses of the infective
      agent, Dcn(-/-) mice had fewer Borrelia-positive cultures from most tissues
      analyzed than did Dcn(+/+) or Dcn(+/-) mice. When the infection dose was
      increased, similar differences were not observed in most tissues but were seen in
      bacterial colonization of joints and the extent of Borreila-induced arthritis.
      Quantitative PCR demonstrated that joints harvested from Dcn(-/-) mice had
      diminished Borrelia numbers compared with issues harvested from Dcn(+/+)
      controls. Histological examination also revealed a low incidence and severity of
      arthritis in Dcn(-/-) mice. Conversely, no differences in the numbers of Borreila
      positive skin cultures were observed among the different genotypes regardless of
      the infection dose. These differences, which were observed regardless of genetic
      background of the mice (BALB/c or C3H/HeN) or method of infection, demonstrate
      the importance of decorin in the pathogenesis of LD.

PMID- 11285304
TI  - A hydroxyl radical-like species oxidizes cynomolgus monkey artery wall proteins
      in early diabetic vascular disease.
AB  - Recent evidence argues strongly that the marked increase in risk for
      atherosclerotic heart disease seen in diabetics cannot be explained by a
      generalized increase in oxidative stress. Here, we used streptozotocin to induce
      hyperglycemia in cynomolgus monkeys for 6 months and tested whether high glucose
      levels promote localized oxidative damage to artery wall proteins. We focused on
      three potential agents of oxidative damage: hydroxyl radical, tyrosyl radical,
      and reactive nitrogen species. To determine which pathways operate in vivo, we
      quantified four stable end products of these reactants -- ortho-tyrosine, meta
      tyrosine, o,o'-dityrosine, and 3-nitrotyrosine -- in aortic proteins. Levels of
      ortho-tyrosine, meta-tyrosine, and o,o'-dityrosine, but not of 3-nitrotyrosine,
      were significantly higher in aortic tissue of hyperglycemic animals. Of the
      oxidative agents we tested, only hydroxyl radical mimicked this pattern of
      oxidized amino acids. Moreover, tissue levels of ortho-tyrosine and meta-tyrosine
      correlated strongly with serum levels of glycated hemoglobin, a measure of
      glycemic control. We conclude that short-term hyperglycemia in primates promotes
      oxidation of artery wall proteins by a species that resembles hydroxyl radical.
      Our observations suggest that glycoxidation reactions in the arterial
      microenvironment contribute to early diabetic vascular disease, raising the
      possibility that antioxidant therapies might interrupt this process.

PMID- 11285305
TI  - Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediated by
      reciprocal secretion of adenosine and IL-6.
AB  - Adenosine is formed in the intestinal lumen during active inflammation from
      neutrophil-derived 5' AMP. Using intestinal epithelial cell line T84, we studied
      the effect of adenosine on the secretion of IL-6, a proinflammatory cytokine
      involved in neutrophil degranulation and lymphocyte differentiation. Stimulation
      of T84 monolayers with either apical or basolateral adenosine induces A2b
      receptor-mediated increase in IL-6 secretion, which is polarized to the apical
      (luminal) compartment. In addition, Salmonella typhimurium, TNF-alpha, and
      forskolin, known inducers of IL-6 secretion in intestinal epithelial cells, also
      stimulate IL-6 secretion into the apical compartment. We show that IL6 promoter
      induction by adenosine occurs through cAMP-mediated activation of nuclear cAMP
      responsive element-binding protein (CREB). We also show that IL-6 released in the
      luminal (apical) compartment achieves a sufficient concentration to activate
      neutrophils (from which the adenosine signal originates), since such IL-6 is
      found to induce an intracellular [Ca(++)] flux in neutrophils. We conclude that
      adenosine released in the intestinal lumen during active inflammation may induce
      IL-6 secretion, which is mediated by cAMP/CREB activation and occurs in an
      apically polarized fashion. This would allow sequential activation of neutrophil
      degranulation in the lumen -- a flow of events that would, in an epithelium
      dependent fashion, enhance microbicidal activity of neutrophils as they arrive in
      the intestinal lumen.

PMID- 11285306
TI  - The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model.
AB  - MHC class II molecules are critical determinants of genetic susceptibility to
      human type 1 diabetes. In patients, the most common haplotype contains the
      DRA1*0101-DRB1*0401 (DR4) and DQA1*0301-DQB1*0302 (DQ8) loci. To assess directly
      the relative roles of HLA-DQ8 and DR4 for diabetes development in vivo, we
      generated C57BL/6 transgenic mice that lack endogenous mouse MHC class II
      molecules but express HLA-DQ8 and/or DR4. Neither HLA-DQ nor HLA-DR transgenic
      mice developed insulitis or spontaneous diabetes. However, when they were crossed
      to transgenic mice (C57BL/6) expressing the B7.1 costimulatory molecules on
      pancreatic beta cells that do not normally develop diabetes, T cells from these
      double transgenic mice were no longer tolerant to islet autoantigens. The
      majority of DQ8/RIP-B7 mice developed spontaneous diabetes, whereas only 25% of
      DR4/RIP-B7 mice did so. Interestingly, when DQ8 and DR4 were coexpressed
      (DQ8DR4/RIP-B7), only 23% of these mice developed diabetes, an incidence
      indistinguishable from the DR4/RIP-B7 mice. T cells from both DR4/RIP-B7 and
      DQ8DR4/RIP-B7 mice, unlike those from DQ8/RIP-B7 mice, exhibited a Th2-like
      phenotype. Thus, the expression of DR4 appeared to downregulate DQ8-restricted
      autoreactive T cells in DQ8DR4/RIP-B7 mice. Our data suggest that although both
      DQ8 and DR4 can promote spontaneous diabetes in mice with a non-autoimmune-prone
      genetic background, the diabetogenic effect of the DQ8 allele is much greater,
      whereas DR4 expression downregulates the diabetogenic effect of DQ8, perhaps by
      enhancing Th2-like immune responses.

PMID- 11285307
TI  - B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4.
AB  - To examine whether B7 costimulation can be mediated by a molecule on T cells that
      is neither CD28 nor CTLA4, we generated mice lacking both of these receptors.
      CD28/CTLA4(-/-) mice resemble CD28(-/-) mice in having decreased expression of T
      cell activation markers in vivo and decreased T-cell proliferation in vitro, as
      compared with wild-type mice. Using multiple approaches, we find B7-dependent
      costimulation in CD28/CTLA4(-/-) mice. The proliferation of CD28/CTLA4(-/-) T
      cells is inhibited by CTLA4-Ig and by the use of antigen-presenting cells lacking
      both B7-1 and B7-2. CD28/CTLA4(-/-) T-cell proliferation is increased by exposure
      to Chinese hamster ovary cells transfected with B7-1 or B7-2. Finally,
      administration of CTLA4-Ig to CD28/CTLA4(-/-) cardiac allograft recipients
      significantly prolongs graft survival. These data support the existence of an
      additional receptor for B7 molecules that is neither CD28 nor CTLA4.

PMID- 11285308
TI  - Immunohistochemical and functional correlations of renal cyclooxygenase-2 in
      experimental diabetes.
AB  - Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been
      implicated in the pathological renal hemodynamics and structural alterations in
      diabetes mellitus, but the role of individual COX isoenzymes in diabetic
      nephropathy remains unknown. We explored COX-1 and COX-2 expression and
      hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2
      inhibitor NS398 in moderately hyperglycemic, streptozotocin-diabetic (D) and
      control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C
      rats and normalized by improved glycemic control. Acute systemic administration
      of NS398 induced no significant changes in mean arterial pressure and renal
      plasma flow in either C or D rats but reduced glomerular filtration rate in D
      rats, resulting in a decrease in filtration fraction. VS had no effect on renal
      hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE(2).
      However, only NS398 reduced excretion of thromboxane A(2). In conclusion, we
      documented an increase in renal cortical COX-2 protein expression associated with
      a different renal hemodynamic response to selective systemic COX-2 inhibition in
      D as compared with C animals, indicating a role of COX-2-derived PG in
      pathological renal hemodynamic changes in diabetes.

PMID- 11285309
TI  - A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by
      affecting bone density and quality.
AB  - Osteoporosis is a common disease with a strong genetic component. We previously
      described a polymorphic Sp1 binding site in the COL1A1 gene that has been
      associated with osteoporosis in several populations. Here we explore the
      molecular mechanisms underlying this association. A meta-analysis showed
      significant associations between COL1A1 "s" alleles and bone mineral density
      (BMD), body mass index (BMI), and osteoporotic fractures. The association with
      fracture was stronger than expected on the basis of the observed differences in
      BMD and BMI, suggesting an additional effect on bone strength. Gel shift assays
      showed increased binding affinity of the "s" allele for Sp1 protein, and primary
      RNA transcripts derived from the "s" allele were approximately three times more
      abundant than "S" allele--derived transcripts in "Ss" heterozygotes. Collagen
      produced from osteoblasts cultured from "Ss" heterozygotes had an increased ratio
      of alpha 1(I) protein relative to alpha 2(I), and this was accompanied by an
      increased ratio of COL1A1 mRNA relative to COL1A2. Finally, the yield strength of
      bone derived from "Ss" individuals was reduced when compared with bone derived
      from "SS" subjects. We conclude that the COL1A1 Sp1 polymorphism is a functional
      genetic variant that predisposes to osteoporosis by complex mechanisms involving
      changes in bone mass and bone quality.

PMID- 11285310
TI  - Regulatory functions of self-restricted MHC class II allopeptide-specific Th2
      clones in vivo.
AB  - We studied T-cell clones generated from grafts of rejecting and tolerant animals
      and investigated the regulatory function of Th2 clones in vitro and in vivo. To
      prevent allograft rejection, we treated LEW strain recipient rats of WF strain
      kidney grafts with CTLA4Ig to block CD28-B7 costimulation. We then isolated
      epitope-specific T-cell clones from the engrafted tissue, using a donor-derived
      immunodominant class II MHC allopeptide presented by recipient antigen-presenting
      cells. Acutely rejected tissue from untreated animals yielded self-restricted,
      allopeptide-specific T-cell clones that produced IFN-gamma, whereas clones from
      tolerant animals produced IL-4 and IL-10. Adoptive transfer into naive recipients
      of Th1 clones, but not Th2 clones, induced alloantigen-specific delayed-type
      hypersensitivity (DTH) responses. In addition, Th2 clones suppressed DTH
      responses mediated by Th1 clones in vivo and blocked Th1 cell proliferation and
      IFN-gamma production in vitro. A pilot human study showed that HLA-DR allopeptide
      specific T-cell clones generated from patients with chronic rejection secrete Th1
      cytokines, whereas those from patients with stable graft function produce Th2
      cytokines in response to donor-specific HLA-DR allopeptides. We suggest that self
      restricted alloantigen-specific Th2 clones may regulate the alloimmune responses
      and promote long-term allograft survival and tolerance.

PMID- 11285311
TI  - Laminar flow inhibits TNF-induced ASK1 activation by preventing dissociation of
      ASK1 from its inhibitor 14-3-3.
AB  - The inflammatory cytokine TNF-alpha stimulates several presumed pro-atherogenic
      signaling events in endothelial cells (ECs), including activation of c-Jun NH(2)
      terminal kinase (JNK) and induction of E-selectin. Here, we show that apoptosis
      signal-regulating kinase 1 (ASK1), a MAP kinase kinase kinase, is required for
      TNF-mediated JNK activation. TNF activates ASK1 in part by dissociating ASK1 from
      its inhibitor 14-3-3. Because the risk of atherosclerosis is decreased in regions
      of steady laminar flow, we hypothesized that laminar flow inhibits
      proinflammatory cytokine-mediated activation of JNK. Steady laminar flow
      inhibited both TNF activation of ASK1 and JNK. Inhibition of ASK1 by flow
      correlated with increased association of ASK1 with 14-3-3. A constitutively
      active form of ASK1 lacking the 14-3-3-binding site (ASK1-Delta NS967A) was not
      inhibited by flow. These data establish ASK1 as a target for flow-mediated
      inhibition of cytokine signaling and indicate a novel role for 14-3-3 as an anti
      inflammatory mediator in ECs.

PMID- 11285312
TI  - Polyunsaturated fatty acids and epidermal growth factor receptor/mitogen
      activated protein kinase signaling in mammary cancer.
AB  - Mammary cancer is the second leading cause of cancer death in women, the second
      most common neoplasm in dogs and the third leading neoplasm in cats. Mammary
      tumors are similar in morphology and progression in these species, so cats and
      dogs are good models for determining treatment or prevention modalities for the
      human population. Epidemiological, in vitro and rodent studies have demonstrated
      that polyunsaturated fatty acids (PUFA) can influence the growth, progression and
      metastasis of mammary cancer. Although a role of PUFA in modulating mammary
      cancer growth has been shown, the mechanisms by which this occurs remain unclear.
      Recent studies have demonstrated that PUFA may influence the activity of the
      epidermal growth factor receptor/mitogen-activated protein kinase pathway, which
      is involved in regulating several oncogenes (c-myc, c-fos, neu/c-erb-b2) involved
      in the progression of cancer. We review the potential mechanism by which PUFA may
      modulate the growth of mammary cancer through regulation of the epidermal growth
      factor receptor/mitogen-activated protein kinase signal transduction cascade.

PMID- 11285313
TI  - Polyunsaturated fatty acid regulation of gene transcription: a molecular
      mechanism to improve the metabolic syndrome.
AB  - This review addresses the hypothesis that polyunsaturated fatty acids (PUFA),
      particularly those of the (n-3) family, play pivotal roles as "fuel partitioners"
      in that they direct fatty acids away from triglyceride storage and toward
      oxidation, and that they enhance glucose flux to glycogen. In doing this, PUFA
      may protect against the adverse symptoms of the metabolic syndrome and reduce the
      risk of heart disease. PUFA exert their beneficial effects by up-regulating the
      expression of genes encoding proteins involved in fatty acid oxidation while
      simultaneously down-regulating genes encoding proteins of lipid synthesis. PUFA
      govern oxidative gene expression by activating the transcription factor
      peroxisome proliferator-activated receptor alpha. PUFA suppress lipogenic gene
      expression by reducing the nuclear abundance and DNA-binding affinity of
      transcription factors responsible for imparting insulin and carbohydrate control
      to lipogenic and glycolytic genes. In particular, PUFA suppress the nuclear
      abundance and expression of sterol regulatory element binding protein-1 and
      reduce the DNA-binding activities of nuclear factor Y, Sp1 and possibly hepatic
      nuclear factor-4. Collectively, the studies discussed suggest that the fuel
      "repartitioning" and gene expression actions of PUFA should be considered among
      criteria used in defining the dietary needs of (n-6) and (n-3) and in
      establishing the dietary ratio of (n-6) to (n-3) needed for optimum health
      benefit.

PMID- 11285314
TI  - Is wasting (thinness) a hidden problem in Latin America's children?

PMID- 11285315
TI  - Actions and interactions of thyroid hormone and zinc status in growing rats.
AB  - Both thyroid hormone (triiodo-L-thyronine, T3) and zinc play important roles in
      growth and development. The T3 receptor is thought to require zinc to adopt its
      biologically active conformation. Some of the effects of zinc deficiency,
      therefore, may be due to loss of zinc from the T3 receptor and impairment of T3
      action. This possibility was investigated in growing rats by examining the
      effects of hypothyroidism and hyperthyroidism in zinc-deficient, pair-fed and
      control rats. Measurement of serum zinc and T3 confirmed the efficacy of the
      treatments. Zinc deficiency and hypothyroidism resulted in lower food intake and
      growth failure, but no interaction was observed between the two treatments.
      Individual tissue weights were influenced by thyroid status as expected,
      regardless of zinc status. Both dietary and hormonal treatments influenced serum
      insulin-like growth factor (IGF)-I in an interactive manner. IGF-I was reduced to
      a greater extent in zinc-deficient than in pair-fed rats compared with controls.
      Both hypothyroidism and hyperthyroidism reduced serum IGF-I, and a greater
      reduction due to hyperthyroidism was apparent in zinc-deficient rats. IGF binding
      proteins were also influenced by diet and thyroid status. The hepatic expression
      of mRNA S14 was assessed as a direct index of the nuclear action of T3, but its
      response was not influenced by dietary treatment. Although confirming the role of
      both T3 and zinc in the regulation of growth and the somatotrophic axis, the
      growth failure of zinc deficiency does not appear to be due to impaired T3
      function.

PMID- 11285316
TI  - Reduced growth and skeletal changes in zinc-deficient growing rats are due to
      impaired growth plate activity and inanition.
AB  - We investigated the effects of dietary zinc deficiency on skeletal metabolism in
      an animal model. Thirty 21-d-old male Sprague-Dawley rats were fed for 28 d
      either a zinc-deficient (ZD) diet (1 mg zinc/kg) or a normal diet ad libitum (AL,
      50 mg zinc/kg) or in the same quantity as the ZD (pair-fed, PF). Only in the ZD
      group were general physical signs of zinc deficiency observed. Compared with the
      AL and PF rats, ZD rats showed significantly lower mean values in ponderal growth
      rate, femur weight and length, circulating levels of insulin-like growth factor
      I, bone mechanical properties and concentration of zinc and, on histomorphometry,
      a decrease in the thicknesses of the overall growth plate and hypertrophic
      cartilage. In contrast, although bone volume was significantly lower in the ZD
      and PF rats than in the AL rats, no difference was observed between the ZD and PF
      rats. Osteoclast surface/bone surface and osteoclast number/bone surface ratios
      were significantly greater in PF rats than in the other two groups and not
      different in ZD and AL rats. Collectively, these data indicate that zinc
      deficiency has profound effects on the skeletal system of growing rats. In
      particular, the effects of zinc deficiency on bone growth and mass are the result
      of the reduced activity of the growth plate, likely mediated by impairment in the
      insulin-like growth factor-I system. We did not demonstrate an effect on bone
      mass via increased bone resorption.

PMID- 11285317
TI  - Docosahexaenoic acid suppresses function of the CD28 costimulatory membrane
      receptor in primary murine and Jurkat T cells.
AB  - (n-3) polyunsaturated fatty acids (PUFA) have been widely documented to reduce
      inflammation in diseases such as rheumatoid arthritis. This study sought to
      elucidate the mechanism whereby (n-3) PUFA downregulate T-cell proliferation. We
      hypothesized that membrane incorporation of dietary PUFA would alter membrane
      structure and consequently membrane receptor function. Female C57BL/6 mice were
      fed for 14 d one of three diets containing arachidonic acid (AA), fish oil or
      docosahexaenoic acid (DHA) that varied in lipid composition only. Spleens were
      harvested and T cells ( approximately 90% purity) were activated with agonists
      that stimulated proliferation at the receptor level [anti-CD3 (alphaCD3)/anti
      CD28 (alphaCD28)], intracellularly [phorbol-12-myristate-13-acetate
      (PMA)/ionomycin] or with a combined receptor/intracellular agonist
      (alphaCD3/PMA). Although there was no significant difference (P > 0.05) in
      proliferative response across dietary groups within each agonist set, interleukin
      (IL)-2 secretion was significantly reduced (P = 0.05) in cells from DHA-fed mice
      stimulated with alphaCD3/alphaCD28. In parallel in vitro experiments, Jurkat T
      cells were incubated with 50 micromol/L linoleic acid, AA, or DHA. Similar
      agonists sets were employed, and cells incubated with DHA and AA had a
      significantly reduced (P < 0.05) IL-2 secretion in three of the agonist sets.
      However, only when the CD28 receptor was stimulated was there a significant
      difference (P < 0.05) between DHA and AA. The results of this study suggest the
      involvement of the CD28 receptor in reducing IL-2 secretion in DHA-fed mice and
      DHA-incubated Jurkat cells and that purified T cells from DHA-fed mice require
      accessory cells to modulate proliferative suppression.

PMID- 11285318
TI  - Genistein, daidzein and glycitein inhibit growth and DNA synthesis of aortic
      smooth muscle cells from stroke-prone spontaneously hypertensive rats.
AB  - Recent studies have reported that estrogen replacement therapy (ERT) reduces the
      risk of cardiovascular diseases in postmenopausal women. However, mechanisms
      responsible for this effect are not yet completely understood, and ERT is
      associated with carcinogenic side effects in women and feminizing effects in men.
      Because soybean isoflavones, a group of natural phytoestrogens, have only weak
      estrogenic activity and are not known to have side effects such as carcinogenesis
      and feminization, we evaluated the effects of genistein, daidzein and glycitein
      on the growth and DNA synthesis of aortic smooth muscle cells (SMC) from stroke
      prone spontaneously hypertensive rats (SHRSP). SMC were cultured in dishes and
      proliferated on 10% dextran-coated charcoal/fetal bovine serum, and then treated
      with 0.1-30 micromol/L of genistein, daidzein or glycitein to investigate cell
      proliferation (cell number) and DNA synthesis (cell proliferation ELISA system),
      respectively. We also studied their effects on platelet-derived growth factor
      (PDGF)-BB (20 microg/L)-induced SMC proliferation. Soybean isoflavones inhibited
      proliferation and DNA synthesis of SMC from SHRSP in a concentration-dependent
      manner. Inhibition was significant at 3 micromol/L of genistein and 10 micromol/L
      of both daidzein and glycitein. For significant inhibition of PDGF-BB-induced SMC
      proliferation, concentrations as low as 0.1 micromol/L of each isoflavone were
      effective. These isoflavones, with their inhibitory effects on natural and PDGF
      BB-induced SMC proliferation, may be useful in attenuatating such proliferation,
      a basic mechanism involved in atherosclerotic vascular change, thereby preventing
      atherosclerotic cardiovascular diseases.

PMID- 11285319
TI  - Reduced hepatic triglyceride secretion in rats fed docosahexaenoic acid-rich fish
      oil suppresses postprandial hypertriglyceridemia.
AB  - To evaluate the mechanisms of suppression of postprandial hypertriglyceridemia by
      fish oil rich in docosahexaenoic acid, the effect on the intestinal absorption of
      triglyceride, activities of lipoprotein lipase (LPL) and hepatic triglyceride
      lipase (HTGL) and metabolism of chylomicrons (CM) and CM remnants were compared
      with that of safflower oil in Sprague-Dawley rats in a series of studies. The
      feeding of fish oil for 3 wk suppressed postprandial hypertriglyceridemia (study
      1). Dietary fish oil did not alter the rate of lymphatic absorption of
      triglyceride (study 2). The activities of LPL and HTGL were measured at 5 h after
      the beginning of feeding, when serum triglyceride concentrations were highest in
      both dietary groups. The activities of LPL in adipose tissue and heart were
      greater (P < 0.05) and those of HTGL were lower (P < 0.05) in the rats fed fish
      oil (study 3). In contrast, there were no differences in the activities of LPL
      and HTGL in postheparin plasma between the fish and safflower oil groups (study
      4). The clearance rates of CM and CM remnants were measured by injecting
      intravenously CM collected from rats fed safflower or fish oils with
      [14C]triolein and [3H]cholesterol (study 5). Dietary oil did not influence the
      half-lives of CM or CM remnants. The secretion of triglyceride from the liver of
      rats injected with Triton WR-1339 was lower (P < 0.05) in the rats fed
      docosahexaenoic acid, a major component of fish oil, than those fed linoleic
      acid, a major component of safflower oil (study 6). These observations strongly
      support the hypothesis that in rats, the principal cause of the suppression of
      postprandial hypertriglyceridemia by fish oil is the depression of triglyceride
      secretion from the liver.

PMID- 11285320
TI  - Dietary ribonucleotides modulate type 1 and type 2 T-helper cell responses
      against ovalbumin in young BALB/cJ mice.
AB  - Dietary ribonucleotides have been shown to augment type 1 T-helper cell (Th1)
      responses to a protein antigen (Ag) in Th1-prone C57BL/6 mice, but their effects
      on type 2 Th (Th2)-prone mice are unknown. BALB/cJ mice have skewed Th2 responses
      against ovalbumin (OVA), characterized by augmented production of Th2 cytokines
      and immunoglobulin (Ig)G1/IgE antibodies (Ab); Th1 responses augment IgG2a Ab
      production, whereas Th2 responses augment IgG1/IgE Ab production. In this study,
      we determined the effects of dietary ribonucleotides obtained from yeast on the
      balance of Th1/Th2 responses against OVA in young BALB/cJ mice. Mice were fed a
      ribonucleotide-free (NF) or ribonucleotide-supplemented (NS) diet (4.74 g
      nucleotides/kg diet) and given OVA (10 microg/dose) with incomplete Freund's
      adjuvant (IFA) at 3 and 6 wk. We assessed T-cell responses in the regional
      draining lymph nodes (LN) by measuring production and expression of Th1/Th2
      cytokines, interferon-gamma (IFN-gamma) and interleukin-5 (IL-5), respectively.
      Anti-OVA IgG subclass and IgE Ab levels were determined 3 wk after the first OVA
      challenge and 5 d and 2 wk after the second OVA challenge. Dietary
      ribonucleotides significantly augmented OVA-specific IFN-gamma production by the
      regional draining LN cells after the first and second OVA challenges. The NS diet
      increased anti-OVA IgG2a Ab levels after the first OVA challenge and both anti
      OVA IgG2a and anti-OVA IgG2b after the second challenge. OVA-specific IgG1 and
      IgE Ab levels were lower (P < 0.05) after the second OVA challenge in mice fed
      the NS diet. Dietary ribonucleotides did not affect production or expression of
      IL-5. Our findings thus indicate that in Th2-prone BALB/c J mice, dietary
      ribonucleotides modulated skewed Th2 responses against OVA toward Th1 as measured
      by production of IFN-gamma, a Th1 cytokine, and changes in anti-OVA Ab isotype
      levels.

PMID- 11285321
TI  - Oral administration of leucine stimulates ribosomal protein mRNA translation but
      not global rates of protein synthesis in the liver of rats.
AB  - The objective of the current study was to examine the role of the branched-chain
      amino acid (BCAA) leucine in the regulation of hepatic protein synthesis and
      ribosomal protein (rp) mRNA translation in vivo. Food-deprived (18 h) male rats
      (200 g) were orally administered saline (control) or 270 mg leucine, isoleucine
      or valine and killed 1 h later. Administration of any BCAA resulted in enhanced
      phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E
      BP1) compared with controls. However, leucine was the most effective at
      stimulating phosphorylation of 4E-BP1 as well as the 70-kDa ribosomal protein S6
      kinase (S6K1). Despite these effects on components of the translation initiation
      process, there were no differences in total protein synthesis rates among
      treatment groups. The distribution of rp (S4, S8, L26) and non-rp (albumin, beta
      actin) mRNAs across sucrose density gradients showed that the preponderance of
      hepatic rp mRNAs in control rats was unloaded from polysomes. Of the BCAA, only
      leucine was the most effective in causing a shift in the distribution of rp mRNA
      to polysomes compared with controls. Non-rp transcripts remained mainly polysome
      associated under all conditions. These results suggest that leucine is most
      effective among the BCAA in its ability to stimulate translation of rp mRNA in
      liver. Furthermore, the translation of rp mRNA is disjointed from rates of total
      protein synthesis in liver and related to the degree of S6K1 phosphorylation.

PMID- 11285322
TI  - Serum aminopeptidase A activity of mice is related to dietary fat saturation.
AB  - A high intake of monounsaturated fat has been proposed to be a dietary factor
      that can decrease the incidence of cardiovascular disease and hypertension. In
      addition, increasing dietary fat saturation has been shown to increase plasma
      total cholesterol and elevate systolic and diastolic blood pressures. We
      demonstrated previously that cholesterol selectively increases in vitro
      aminopeptidase A activity, which is related to angiotensin metabolism. In this
      study, we investigated the effect of different degrees of dietary fatty acid
      saturation on serum aminopeptidase activities in vivo. Serum total cholesterol
      concentrations were also measured. Five groups of male Balb/C mice were fed for
      10 wk diets containing 2.4 g/100 g of sunflower oil, fish oil, olive oil, lard or
      coconut oil. We measured alanyl-, arginyl-, cystinyl-, pyroglutamyl-, aspartyl-
      and glutamyl-specific aminopeptidase activities using arylamides as substrates.
      Serum total cholesterol levels were higher in mice fed diets containing saturated
      oils (lard and coconut) than in those consuming sunflower oil, which is
      unsaturated. Two of the serum aminopeptidase A activities (aspartyl and glutamyl
      aminopeptidase) increased progressively with the degree of saturation of the
      dietary fatty acids; activities were significantly greater in mice fed coconut
      oil than in those fed sunflower or fish oil. Therefore, the substrates hydrolyzed
      by this activity as well as their functions may be similarly affected. These
      results may have some implication for the treatment of cardiovascular disease.

PMID- 11285323
TI  - Inducibility of hepatic CYP1A enzymes by 3-methylcholanthrene and isosafrole
      differs in male rats fed diets containing casein, soy protein isolate or whey
      from conception to adulthood.
AB  - Hepatic cytochrome P450 (CYP)1A1 and 1A2 enzymes were studied in male Sprague
      Dawley rats derived from 5-7 litters fed diets in which the protein source was
      casein, soy protein isolate or whey. At age 65 d, rats were gavaged with corn oil
      (vehicle), 40 mg/kg 3-methylcholanthrene (3-MC) or 75 mg/kg isosafrole (ISO).
      Hepatic expression of CYP1A1 and CYP1A2 mRNA, apoprotein and associated
      monooxygenase activities were measured 17 h later. No significant dietary effects
      were observed on basal expression of either enzyme. However, interactions between
      diet and the two inducers (3-MC and ISO) were observed in soy-fed rats for ethoxy
      and methoxyresorufin O-dealkylase activity, CYP1A1 and CYP1A2 apoprotein and
      mRNA (P < 0.05). The level of induction of CYP1A1 mRNA and apoprotein was lower
      in rats fed soy diets than in rats fed casein diets (P < 0.05), and the level of
      induced CYP1A2 mRNA was lower in rats fed soy or whey (P < 0.05) after treatment
      with the aryl hydrocarbon (Ah) receptor-dependent inducer 3-MC. This was
      accompanied by a 50% reduction in constitutive levels of the Ah receptor in liver
      cytosol of soy-fed, relative to casein-fed rats, and a slightly smaller reduction
      in whey-fed rats. Expression of the Ah receptor correlated with 3-MC-inducibility
      of CYP1A1 mRNA in rats fed the three diets. In contrast, in rats induced with
      ISO, which does not bind to the Ah receptor and induces CYP1As via different
      mechanisms than 3-MC, ethoxyresorufin O-deethylase activity and levels of CYP1A1
      apoprotein and mRNA were elevated to a greater degree in soy-fed than in casein-
      or whey-fed rats (P < 0.05). Moreover, after ISO treatment, induction of
      methoxyresorufin O-demethylase activity, CYP1A2 apoprotein and mRNA levels was
      observed only in rats fed soy (P < 0.05). These data suggest potential effects of
      dietary protein source on metabolism of a wide variety of CYP1A substrates,
      including environmental and dietary carcinogens, many of which induce their own
      metabolism.

PMID- 11285324
TI  - Vitamin A deficiency reduces insulin-like growth factor (IGF)-I gene expression
      and increases IGF-I receptor and insulin receptor gene expression in tissues of
      Japanese quail (Coturnix coturnix japonica).
AB  - The insulin-like growth factor (IGF) system is regulated by various stimuli,
      including hormones, growth factors and nutritional status. We examined the
      effects of vitamin A on components of the IGF system in Japanese quail. Male
      quail (1 d old) fed a vitamin A-deficient diet for 14 or 21 d developed vitamin A
      deficiency, as confirmed by a depletion of serum retinol and hepatic retinyl
      palmitate. Consuming the vitamin A-deficient diet for 14 d did not affect growth
      rate, but decreased the serum IGF-I concentrations by 22% compared with the
      control group. The decreased serum IGF-I levels were accompanied by 21-52% lower
      levels of IGF-I mRNA in the testis, lung, liver and heart, whereas IGF-I receptor
      (IGF-IR) and insulin receptor (IR) gene expressions were unaffected in these
      tissues. Continuous feeding of the vitamin A-deficient diet for 21 d retarded
      growth and further decreased the levels of serum IGF-I and tissue IGF-I mRNA.
      Serum IGF-I levels were reduced by approximately 50%; IGF-I mRNA levels were >
      90% lower in the liver and lung and approximately 60% lower in the heart and
      testis. In contrast, levels of the IGF-IR and IR mRNAs were approximately 100%
      greater in some tissues examined. When vitamin A-deficient quail received a
      single injection of retinol or retinoic acid (0.1 mg/bird), tissue IGF-I, IGF-IR
      and IR gene expressions did not change after 4 h. These results suggest a
      possible physiologic role of the IGF system in mediating vitamin A-supported
      growth of Japanese quail.

PMID- 11285325
TI  - Corn and sesame oils increase serum gamma-tocopherol concentrations in healthy
      Swedish women.
AB  - We studied the effects of dietary intervention with three vegetable oils (Linola,
      corn or sesame oil, all good sources of gamma-tocopherol) on absolute and
      relative concentrations of alpha- and gamma-tocopherol in human serum. The oils
      contained only small amounts of linolenic acid but varying amounts of oleic and
      linoleic acids, and they had different concentrations of alpha-tocopherol. Forty
      healthy female students (mean age 26 y) were randomly assigned to one of three
      groups and consumed a diet that contained one of the three oils for 4 wk. Refined
      oils were distributed as ingredients in specially prepared buns, in margarine or
      as dressing. Serum tocopherols, serum lipoproteins and plasma malondialdehyde
      concentrations were measured. The gamma-tocopherol concentrations normalized to
      serum lipids increased significantly in the corn and sesame oil groups (P <
      0.01), and the alpha-/gamma-tocopherol ratios decreased significantly from
      baseline concentrations in all groups (P < 0.05). The alpha-tocopherol
      concentrations did not change during the diet period in any of the three groups.
      Serum cholesterol, serum apolipoprotein B and plasma malondialdehyde
      concentrations decreased significantly only in the Linola oil group (P < 0.05).
      These data show that a moderately modified natural diet that contains both alpha-
      and gamma-tocopherol increases the serum gamma-tocopherol concentration in
      healthy women without affecting the serum alpha-tocopherol concentration.

PMID- 11285326
TI  - Usual dietary isoflavone intake is associated with cardiovascular disease risk
      factors in postmenopausal women.
AB  - Intervention data suggest a cardioprotective role for supplemental isoflavones;
      however, few studies have examined the cardiovascular disease (CVD) benefit of
      usual dietary isoflavone intake. This cross-sectional study examined the
      association between usual dietary isoflavone intake and CVD risk factors,
      including lipids and lipoproteins, body mass index (BMI) and fat distribution,
      blood pressure, glucose and insulin. Subjects were postmenopausal women (n = 208)
      aged 45-74 y, who attended screening and baseline visits for a randomized, double
      blind, placebo-controlled trial examining the effects of isoflavone use. At
      screening, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol
      were measured, and demographic, behavioral and menopausal characteristics were
      assessed. One month later, dietary intake over the past year was assessed with a
      standardized questionnaire. Anthropometric measurements and blood pressure were
      obtained, and a 75-g oral glucose tolerance test was administered. Isoflavone
      consumption did not vary by age, exercise, smoking, education or years
      postmenopausal. Women with high genistein intake had a significantly lower BMI (P
      trend = 0.05), waist circumference (P-trend = 0.05) and fasting insulin (P-trend
      = 0.07) than those with no daily genistein consumption. In adjusted analyses,
      genistein, daidzein and total isoflavone intake were each positively associated
      with HDL cholesterol (P = 0.05) and inversely associated with postchallenge
      insulin (P = 0.05). These data suggest a protective role for dietary soy intake
      against CVD in postmenopausal women.

PMID- 11285327
TI  - Pharmacokinetics of gallic acid and its relative bioavailability from tea in
      healthy humans.
AB  - Gallic acid (GA), a food component that is especially abundant in tea, is an
      antimutagenic, anticarcinogenic and anti-inflammatory agent. We conducted a study
      using acidum gallicum tablets that contained 10% GA and 90% glucose and a black
      tea brew that contained 93% of its GA in free form to determine the
      pharmacokinetics and relative bioavailability of GA in healthy humans. After the
      administration of a single oral dose of acidum gallicum tablets or tea (each
      containing 0.3 mmol GA) to 10 volunteers, plasma and urine samples were collected
      over various time intervals. Concentrations of GA and its metabolite, 4-O
      methylgallic acid (4OMGA), were determined, and the pharmacokinetic parameters
      were calculated. GA from both the tablets and tea was rapidly absorbed and
      eliminated with mean half-lives of 1.19 +/- 0.07 and 1.06 +/- 0.06 h and mean
      maximum concentrations of 1.83 +/- 0.16 and 2.09 +/- 0.22 micromol/L (plasma),
      respectively. After oral administration of the tablets and black tea, 36.4 +/-
      4.5 and 39.6 +/- 5.1% of the GA dose were extracted in urine as GA and 4OMGA,
      respectively. The relative bioavailability of GA from tea compared with that from
      the tablets was 1.06 +/- 0.26, showing that GA is as available from drinking tea
      as it is from swallowing tablets of GA.

PMID- 11285328
TI  - Fermented soybean-derived water-soluble Touchi extract inhibits alpha-glucosidase
      and is antiglycemic in rats and humans after single oral treatments.
AB  - A water-soluble extract of Touchi, a traditional Chinese food, was found to exert
      a strong inhibitory activity against rat intestinal alpha-glucosidase. We orally
      administered sucrose (2 g/kg) with or without Touchi extract (TE) to normal rats
      at 100 and 500 mg/kg. Postprandial increases in blood glucose levels at 30 and 60
      min after the administration of TE were significantly depressed compared with
      controls. In humans, eight borderline diabetic subjects were administered 0.1
      10.0 g TE before sucrose loading (75 g). TE decreased the glycemic response dose
      dependently after sucrose loading. Compared with the area under the curve of the
      postprandial rise in blood glucose with various doses, TE elicited a significant
      antiglycemic effect at a minimum effective dose of 0.3 g. In addition, when four
      diabetics were administered 0.3 g TE before eating 200 g of cooked rice, the
      postprandial increases in blood glucose and mean insulin levels were
      significantly depressed at 60 and 120 min, respectively, after ingestion compared
      with levels when no TE was administered. TE, which exhibits alpha-glucosidase
      inhibitory activity, demonstrated an antihyperglycemic effect and may have
      potential use in the management of patients with non-insulin-dependent diabetic
      mellitus.

PMID- 11285329
TI  - Plasma total homocysteine is influenced by prandial status in humans: the
      Hordaland Hhomocysteine Sstudy.
AB  - Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease,
      adverse pregnancy outcomes and impaired cognitive function. No population-based
      studies on the possible influence of prandial status on tHcy have been published.
      The aim of this study was to investigate the variation in plasma tHcy levels in
      relation to time since last meal. A cross-sectional, population-based study
      including 18,044 individuals in Western Norway was conducted. Most subjects were
      in the age groups 40-42 and 65-67 y. Participants who had not eaten during the
      past 6 h before the blood sampling had significantly higher mean tHcy levels
      compared with those who had eaten; 11.7 [95% confidence interval (CI): 11.4-12.1]
      vs. 11.2 (95% CI: 11.1-11.3) micromol/L among men (P = 0.03) and 10.2 (95% CI:
      9.9-10.6) vs. 9.7 (95% CI: 9.6-9.7) micromol/L among women (P = 0.003). In all
      groups except older women, tHcy concentrations were generally higher with
      increasing time after a meal (P-trend <0.01 in all 3 groups). These findings
      suggest that fasting status and time since last meal may influence levels of tHcy
      and should be considered in studies of tHcy as a risk factor for cardiovascular
      and other diseases, and when comparing tHcy values among studies.

PMID- 11285330
TI  - Intake of micronutrient-rich foods in rural Indian mothers is associated with the
      size of their babies at birth: Pune Maternal Nutrition Study.
AB  - One third of the Indian babies are of low birth weight (<2.5 kg), and this is
      attributed to maternal undernutrition. We therefore examined the relationship
      between maternal nutrition and birth size in a prospective study of 797 rural
      Indian women, focusing on macronutrient intakes, dietary quality and
      micronutrient status. Maternal intakes (24-h recall and food frequency
      questionnaire) and erythrocyte folate, serum ferritin and vitamin C
      concentrations were measured at 18 +/- 2 and 28 +/- 2 wk gestation. Mothers were
      short (151.9 +/- 5.1 cm) and underweight (41.7 +/- 5.1 kg) and had low energy and
      protein intakes at 18 wk (7.4 +/- 2.1 MJ and 45.4 +/- 14.1 g) and 28 wk (7.0 +/-
      2.0 MJ and 43.5 +/- 13.5 g) of gestation. Mean birth weight and length of term
      babies were also low (2665 +/- 358 g and 47.8 +/- 2.0 cm, respectively). Energy
      and protein intakes were not associated with birth size, but higher fat intake at
      wk 18 was associated with neonatal length (P < 0.001), birth weight (P < 0.05)
      and triceps skinfold thickness (P < 0.05) when adjusted for sex, parity and
      gestation. However, birth size was strongly associated with the consumption of
      milk at wk 18 (P < 0.05) and of green leafy vegetables (P < 0.001) and fruits (P
      < 0.01) at wk 28 of gestation even after adjustment for potentially confounding
      variables. Erythrocyte folate at 28 wk gestation was positively associated with
      birth weight (P < 0.001). The lack of association between size at birth and
      maternal energy and protein intake but strong associations with folate status and
      with intakes of foods rich in micronutrients suggest that micronutrients may be
      important limiting factors for fetal growth in this undernourished community.

PMID- 11285331
TI  - Prenatal undernutrition and postnatal growth are associated with adolescent
      thymic function.
AB  - The fetal and early infant origins of a number of adult cardiovascular and
      metabolic diseases have received considerable attention, but the long-term
      consequences of early environments for human immune function have not been
      reported. We investigated the effects of pre- and postnatal environments on
      thymic hormone production in adolescents participating in an ongoing longitudinal
      study in the Philippines. Prospective data collected at birth, during y 1 of
      life, in childhood and in adolescence were used to predict plasma thymopoietin
      concentration in 14- to 15-y-old adolescents (n = 103). Thymopoietin
      concentration was compared for small-for-gestational-age and appropriate-for
      gestational-age individuals while controlling for a range of postnatal exposures.
      Prenatal undernutrition was significantly associated with reduced thymopoietin
      production in interaction with the duration of exclusive breast-feeding (P =
      0.006). Growth in length during y 1 of life was positively associated with
      adolescent thymopoietin production (P = 0.002). These associations remained
      significant after adjusting for a range of potentially confounding variables.
      These findings provide support for the importance of fetal and early infant
      programming of thymic function, and suggest that early environments may have long
      term implications for immunocompetence and adult disease risk.

PMID- 11285332
TI  - Dietary intakes and serum nutrients differ between adults from food-insufficient
      and food-sufficient families: Third National Health and Nutrition Examination
      Survey, 1988-1994.
AB  - Approximately 10.2 million persons in the United States sometimes or often do not
      have enough food to eat, a condition known as food insufficiency. Using cross
      sectional data from the Third National Health and Nutrition Examination Survey
      (NHANES III), we examined whether dietary intakes and serum nutrients differed
      between adults from food-insufficient families (FIF) and adults from food
      sufficient families (FSF). Results from analyses, stratified by age group and
      adjusted for family income and other important covariates, revealed several
      significant findings (P < 0.05). Compared with their food-sufficient
      counterparts, younger adults (aged 20-59 y) from FIF had lower intakes of calcium
      and were more likely to have calcium and vitamin E intakes below 50% of the
      recommended amounts on a given day. Younger adults from FIF also reported lower 1
      mo frequency of consumption of milk/milk products, fruits/fruit juices and
      vegetables. In addition, younger adults from FIF had lower serum concentrations
      of total cholesterol, vitamin A and three carotenoids (alpha-carotene, beta
      cryptoxanthin and lutein/zeaxanthin). Older adults (aged > or =60 y) from FIF had
      lower intakes of energy, vitamin B-6, magnesium, iron and zinc and were more
      likely to have iron and zinc intakes below 50% of the recommended amount on a
      given day. Older adults from FIF also had lower serum concentrations of high
      density lipoprotein cholesterol, albumin, vitamin A, beta-cryptoxanthin and
      vitamin E. Both younger and older adults from FIF were more likely to have very
      low serum albumin (<35 g/L) than were adults from FSF. Our findings show that
      adults from FIF have diets that may compromise their health.

PMID- 11285333
TI  - Unplanned pregnancies are associated with less likelihood of prolonged breast
      feeding among primiparous women in Ghana.
AB  - The objectives of this study were to examine the association between pregnancy
      intentions and the likelihood of breast-feeding and to determine whether parity
      modifies this relationship in Ghana. These cross-sectional analyses were based on
      the last-born children, aged 13-36 mo, of women participating in the 1993
      Ghanaian Demographic and Health Survey. A backward stepwise multivariate logistic
      regression was conducted to examine the relationships after adjusting for child
      age and key confounders (n = 1101). Primiparous women with planned pregnancies
      had a significantly greater median duration of breast-feeding than their
      counterparts whose pregnancies were unintended (21.1 vs. 18.5 mo, respectively).
      Among multiparous women, median breast-feeding duration was similar in both
      groups (21.5 vs. 21 mo). Findings are consistent with results previously reported
      in other cultures and may have implications for breast-feeding promotion
      programs.

PMID- 11285334
TI  - Feeding infant piglets formula with long-chain polyunsaturated fatty acids as
      triacylglycerols or phospholipids influences the distribution of these fatty
      acids in plasma lipoprotein fractions.
AB  - Several sources of long-chain polyunsaturated fatty acids (LCP) are currently
      available for infant formula supplementation. These oils differ in their fatty
      acid composition, the chemical form of the fatty acid esters [triacylglycerols
      (TG) or phospholipids (PL)] and presence of other lipid components. These
      differences may affect LCP absorption, distribution and metabolic fate after
      ingestion. The purpose of the present study was to evaluate the influence of
      different chemical forms of dietary LCP on the composition of plasma, plasma
      lipoproteins, liver and jejunum in infant piglets. Thirty pigs (5 d old) were
      bottle-fed different diets for 4 wk: a control diet (C), a diet containing LCP as
      TG from tuna and fungal oils (TF-TG) or a diet containing LCP as PL from egg yolk
      (E-PL). We measured lipid and fatty acid composition of plasma and lipoproteins,
      as well as lipid composition of liver and intestinal mucosa. The arachidonic and
      docosahexaenoic acids in HDL-PL were significantly higher in piglets fed the E-PL
      diet than in those fed the TF-TG diet. Opposite results were found in the LDL-PL
      diet. No significant differences were found between groups in TG or cholesterol
      concentrations of plasma or lipoproteins. Arachidonic acid in plasma PL and
      cholesteryl esters was significantly higher in the E-PL group than in the TF-TG
      group. The chemical form in which LCP esters are present in different dietary
      sources influences their distribution in plasma lipoproteins. This may be
      important for infant nutrition and suggests that not all LCP sources may be
      biologically equivalent.

PMID- 11285335
TI  - Feeding colostrum, its composition and feeding duration variably modify
      proliferation and morphology of the intestine and digestive enzyme activities of
      neonatal calves.
AB  - We studied the effects of amounts of colostrum consumed on intestinal morphology
      and proliferation and digestive enzyme activities in neonatal calves. Group
      GrCmax calves were fed colostrum from the first milking undiluted on d 1-3 and
      diluted with 25, 50, 75 and 75 parts of a milk replacer on d 4-7. Group GrC1-3
      calves were fed colostrum from milkings 1-6 up to d 3 and then a milk replacer up
      to d 7. Group GrF1-3 calves were fed a milk-based formula (containing only traces
      of growth factors and hormones) up to d 3 and then a milk replacer up to d 7.
      Calves were killed on d 8. Differences in feeding affected villus sizes and
      villus height/crypt depth ratios in the duodenum (GrCmax > GrC1-3), villus areas
      and villus height/crypt depth ratios in the jejunum (GrC1-3 > GrF1-3) and crypt
      depths in the colon (GrF1-3 > GrC1-3). Furthermore, different feeding protocols
      affected the proliferation rates of epithelial cells in the duodenum (GrC1-3 >
      GrCmax; GrC1-3 > GrF1-3) and the jejunum (GrF1-3 > GrC1-3; based on Ki-67
      labeling). Lipase activities in the pancreas were influenced by colostrum feeding
      (GrC(max) > GrC(1-3)). Colostrum intake differentially affected intestinal
      epithelial surface and proliferation and enzyme activities. Feeding high amounts
      of first colostrum seemed to enhance the survival of mature mucosal epithelial
      cells in selected parts of the small intestine, whereas the lack of colostrum
      seemed to decrease epithelial growth.

PMID- 11285336
TI  - Expression of a cloned ovine gastrointestinal peptide transporter (oPepT1) in
      Xenopus oocytes induces uptake of oligopeptides in vitro.
AB  - We determined the primary structure, tissue distribution and in vitro functional
      characterization of a peptide transporter, oPepT1, from ovine intestine. Ovine
      PepT1 (oPepT1) cDNA was 2829-bp long, encoding a protein of 707 amino acid
      residues with an estimated molecular size of 78 kDa and an isoelectric point (pI)
      of 6.57. Transport function of oPepT1 was assessed by expressing oPepT1 in
      Xenopus oocytes using a two-electrode voltage-clamp technique. The transport
      process was electrogenic and pH dependent, but independent of Na+, Cl- and Ca2+.
      The oPepT1 displayed a broad substrate specificity for transport of neutral and
      charged dipeptides and tripeptides. All dipeptides and tripeptides examined
      evoked inward currents in a saturable manner, with an affinity constant (Kt)
      ranging from 27 micromol/L to 3.0 mmol/L. No responses were detected from
      tetrapeptides or free amino acids. Northern blot analysis demonstrated that
      oPepT1 was expressed in the small intestine, omasum and rumen, but was not
      expressed in liver and kidney. The presence of the peptide transporter in the
      forestomach at such levels could provide nutritionally important amino acid
      nitrogen to ruminants.

PMID- 11285337
TI  - The clearance and metabolism of biotin administered intravenously to pigs in
      tracer and physiologic amounts is much more rapid than previously appreciated.
AB  - Understanding of biotin pharmacokinetics and regulation of metabolism is
      essential for the determination of the biotin requirement for humans. Using
      Landrace-Cambrough pigs as a model, we initially demonstrated that biotin binding
      to protein accounts for only a small percentage of the total biotin in plasma. A
      physiologic amount of [14C]biotin was administered intravenously to three pigs;
      nine blood samples were collected over 48 h. Plasma concentrations of 14C-labeled
      metabolites were negligible for the first 2 h after biotin infusion.
      Disappearance curves of total 14C and of [14C]biotin were similar; both fit a
      triexponential function consistent with a three-compartment, open model. To
      characterize the rapid early phase of disappearance more precisely, a physiologic
      amount of [14C]biotin was administered intravenously to five pigs; eight blood
      samples were collected over the first hour and 16 total samples over 48 h. Again
      a triexponential function provided an excellent fit. The mean half-life values
      (+/- 1 SD) for the three phases were 0.11 +/- 0.07, 1.43 +/- 0.42 and 22 +/- 4 h.
      The [14C]biotin accumulated primarily in the liver, kidney and muscle. When
      administered intravenously at tracer doses to three pigs, [3H]biotin exhibited
      similar early pharmacokinetics; however, substantial quantities of a 3H-labeled
      metabolite appeared after 1 h. These studies provide evidence that egress of
      biotin from plasma is more rapid than previously appreciated. The slower second
      and third phases may represent transport into the cytosol, biotransformation into
      intermediates and covalent binding to intracellular proteins. Similar
      pharmacokinetics are likely to be seen in humans.

PMID- 11285338
TI  - Vitamin A intake affects the contribution of chylomicrons vs. retinol-binding
      protein to milk vitamin A in lactating rats.
AB  - To investigate the influence of vitamin A intake on the contribution of
      chylomicrons vs. holo retinol-binding protein to milk vitamin A, female rats were
      fed diets containing either 10 (n = 6) or 50 micromol vitamin A/kg body (n = 4)
      during pregnancy and through d 13 of lactation. [3H]Vitamin A was incorporated
      into each diet beginning on d 6 of lactation. Vitamin A concentrations on d 13
      were significantly higher in dam liver (x 3), pup liver (x 2.6), milk (x 2.5) and
      mammary tissue (x 1.3) in rats consuming the higher level of vitamin A. In both
      groups, vitamin A specific activities in plasma and milk reached apparent
      plateaus by 2.33 d after addition of [3H]vitamin A to the diets. Vitamin A
      specific activity in milk was higher than in plasma at all times in both groups.
      The estimated minimum contribution of chylomicrons to milk vitamin A was 32 +/-
      3% in rats fed the lower level of vitamin A vs. 52 +/- 10% at the higher level (P
      = 0.014). We concluded that dietary vitamin A, like triglycerides, may be
      directed to mammary tissue during lactation for preferential secretion into milk;
      thus, increasing vitamin A intakes will increase the contribution of dietary
      vitamin A to milk. In contrast to milk, mammary tissue vitamin A turns over very
      slowly.

PMID- 11285339
TI  - Class 2 resistant starches lower plasma and liver lipids and improve mineral
      retention in rats.
AB  - The effects of raw potato starch (RPS) and high amylose corn starch (HAS) on
      cecal digestion, lipid metabolism and mineral utilization (Ca and Mg) were
      compared in rats adapted to semipurified diets. The diets provided either 710 g
      wheat starch/100 g diet (control) alone or 510 g wheat starch/100 g diet plus 200
      g resistant starch/100 g (RPS or HAS). Compared with rats fed the control diet,
      significant cecal hypertrophy (240% after 7 d of the fiber consumption) and short
      chain fatty acids accumulation (especially propionic and butyric acids) occurred
      after both resistant starch diets. Apparent Ca, Mg, Zn, Fe and Cu absorptions
      were similarly enhanced by RPS and HAS (50, 50, 27, 21 and 90%, respectively).
      Cholesterol absorption was reduced to 14% of intake in rats fed RPS or HAS
      compared with 47% absorption in control rats. RPS and HAS were also effective in
      lowering plasma cholesterol (-31 and -27%, respectively) and triglycerides (-28
      and -22%, respectively). There was no effect of the diets on cholesterol in d >
      1.040 kg/L lipoproteins (HDL), whereas RPS and HAS depressed cholesterol in d <
      1.040 kg/L lipoproteins (especially in triglyceride-rich lipoproteins). Moreover,
      there were lower concentrations of cholesterol (-50 and -40%, respectively) and
      triglycerides (-53 and -47%, respectively) in the livers of RPS- and HAS-fed
      rats. Thus, RPS and HAS have similar effects on intestinal fermentation, mineral
      utilization and cholesterol metabolism in rats.

PMID- 11285340
TI  - The low prevalence of weight-for-height deficits in Brazilian children is related
      to body proportions.
AB  - Compared with children from other regions, Latin American children living in
      poverty have much lower prevalences of weight-for-height deficits than would be
      expected given the observed rates of stunting. This study was aimed at
      investigating whether variations in body proportions, particularly abdominal
      circumference, could explain this paradoxical finding. In a cross-sectional
      study, children aged 12-35 mo (n = 197) were studied in Southern Brazil. Half of
      these children were from a high socioeconomic status (SES) group whose growth
      closely resembled that of the National Center for Health Statistics (NCHS)/WHO
      reference; the other half were from low income families. The following 11
      anthropometric measurements were collected: weight, height, sitting height/crown
      rump length, head, chest, upper arm and abdominal circumference, triceps, biceps,
      subscapular and suprailiac skinfolds. These measures were compared between the
      two groups of children and with values for North American children [mostly from
      Second National Health and Nutrition Examination Survey (NHANES II)]. For nearly
      all measures, low SES Brazilian children tended to be smaller than both high SES
      and North American children. However, when body proportionality was assessed by
      dividing the measurements by the child's height, these differences tended to
      disappear or even to change direction, as was the case for head, chest and
      abdominal circumferences. Mean abdominal circumference was virtually identical
      between low and high SES children, and the former had larger abdomens for a given
      height. Despite slight differences in measuring techniques, Brazilian children
      had larger abdomens than North Americans. These findings may explain in part why
      deprived Latin American children have higher weights for their height compared
      with the NCHS/WHO reference.

PMID- 11285341
TI  - Vitamin E improves microsomal phospholipase A2 activity and the arachidonic acid
      cascade in kidney of diabetic rats.
AB  - The purpose of the present study was to investigate the effects of vitamin E on
      microsomal phospholipase A2 activity and the arachidonic acid cascade in the
      kidneys of streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats
      weighing 100 +/- 10 g were randomly assigned to one normal and three STZ-induced
      diabetic groups. The diabetic groups were fed a vitamin E-free diet (the DM-0E
      group), 40 mg vitamin E/kg diet (the DM-40E group) or a 400 mg vitamin E/kg diet
      (the DM-400E group). The kidney vitamin E concentrations were 59 and 49% lower in
      the DM-0E and DM-40E groups, respectively, than in the normal group. The kidney
      thiobarbituric acid reactive substance concentrations in the DM-0E, DM-40E and DM
      400E groups were 119, 84 and 33% greater, respectively, than that in the normal
      group. The concentration in the DM-400E group was 39% lower than that in the DM
      0E group. The phospholipase A2 (PLA2) activity in the kidney microsomes of the DM
      0E-40E and DM-400E groups were 88, 58 and 35% greater, respectively, than that in
      the normal group. The activity in the DM-400E group was 28% lower than that in
      the DM-0E group and 16% lower than that in the DM-40E group. The differences in
      the phospholipids in the kidney microsomes included reductions in the
      phosphatidylcholine and phosphatidylethanolamine compositions.
      Phosphatidylethanolamine hydrolysis in the kidney microsomes of the DM-0E and DM
      40E groups were 84 and 64%, which did not differ from the DM-400E group. The
      formation of thromboxane A2 (TXA2) in the kidney microsomes was 137 and 70%
      greater in the DM-0E and DM-40E groups, respectively, than in the normal group.
      TXA2 formation did not differ between the DM-400E and normal groups. The
      formation of prostacyclin in the kidney microsomes was 60 and 44% lower in the DM
      0E and DM-40E groups, respectively, than in the normal group, whereas the DM-400E
      group did not differ from that in the normal group. The ratio of prostacyclin to
      TXA2 was 82 and 65% lower than normal in the DM-0E and DM-40E groups,
      respectively. Kidney function appears to be improved by vitamin E supplementation
      due to its antithrombus action, which in turn controls the arachidonic acid
      cascade system.

PMID- 11285342
TI  - Use of bioimpedance spectroscopy to estimate body water distribution in rats fed
      high dietary sulfur amino acids.
AB  - The effect of dietary sulfur amino acids on bioelectric properties was studied in
      rats by using bioimpedance spectroscopy. Weanling rats were assigned to one of 12
      groups in a factorially arranged experiment with dietary variables of
      supplemental sulfur amino acid (none, 10 g DL-methionine/kg or 10 g DL
      homocystine/kg), pyridoxine hydrochloride (0 or 7.5 mg/kg) and nickel (0 or 1
      mg/kg). After 9 wk of feeding, 20-h urine specimens were collected from food
      deprived rats for measurements of creatinine, and then bioimpedance was measured
      with multifrequency (Hydra ECF/ICF 4200) and single-frequency (RJL Systems model
      101) analyzers. Urinary creatinine excretion was measured by intracellular water
      (ICW), total body solid and urinary volume (R2 = 0.675). Extracellular water
      (ECW) did not add significantly to the model. Rats fed methionine had
      significantly lower total body water, ICW and ECW than rats fed no supplemental
      sulfur amino acid. Rats fed homocystine had significantly lower ECW and a
      significantly higher ratio of ICW to ECW. Rats fed methionine or homocystine had
      significantly lower capacitance corrected for body length and ICW than those fed
      no supplemental sulfur amino acids. These results suggest that dietary
      homocystine changes the distribution of body water and that sulfur amino acids
      can affect membrane porosity and/or membrane thickness.

PMID- 11285343
TI  - Energetic efficiency of starch, protein and lipid utilization in growing pigs.
AB  - Mathematical models are increasingly used to predict the response of an animal to
      a changing nutrient supply. The objective of this experiment was to provide data
      that can be used in model development or evaluation and concerns the energetic
      efficiency with which nutrients are used for protein and lipid deposition. A
      basal diet (D1), limiting in lysine supply, was fed at 1.7 MJ metabolizable
      energy (ME)/(kg BW(0.60) x d1) to growing pigs that weighed approximately 60 kg.
      Four additional diets were formulated: the basal diet and a dietary supplement
      that consisted of starch (D2), starch and corn gluten meal (D3), starch and
      casein (D4) or starch and lipid (D5). The latter four diets were fed at 2.55 MJ
      ME/(kg BW(0.60) x d1) and ensured the same intake of the basal diet across
      treatments; the difference was supplied by the supplement. Metabolic utilization
      of the basal diet and supplements was determined using nitrogen and energy
      balances (indirect calorimetry). The N retention was similar in pigs fed diets
      D1, D2, D3 and D5 but considerably higher in those fed D4. A data analysis model
      was developed to account for differences in ME utilization between nutrients. The
      ME not deposited as protein entered a common pool of energy, which was used for
      adenosine triphosphate synthesis or lipid deposition. The energetic efficiencies
      of ME utilization were 0.842, 0.520 and 0.883 for starch, protein and lipid,
      respectively. Due to the energy cost of protein deposition (or protein turnover),
      the energetic efficiencies of depositing dietary protein as protein or lipid were
      similar.

PMID- 11285344
TI  - Nutrition: a reservoir for integrative science.
AB  - In the last twenty years, powerful new molecular techniques were introduced that
      made it possible to advance knowledge in human biology using a reductionist
      approach. Now, the need for scientists to deal with complexity should drive a
      movement toward an integrationist approach to science. We propose that
      nutritional science is one of the best reservoirs for this approach. The American
      Society for Nutritional Sciences can play an important role by developing and
      delivering a cogent message that convinces the scientific establishment that
      nutrition fills this valuable niche. The society must develop a comprehensive
      strategy to develop our image as the reservoir for life sciences integration. Our
      efforts can start with our national meeting and publications, with the research
      initiatives for which we advocate, with our graduate training programs and with
      the public relations image we project for ourselves. Defining the image and
      future directions of nutrition as the discipline that can integrate scientific
      knowledge from the cell and molecule to the whole body and beyond to populations
      can be the most important task that our society undertakes. If we do not
      effectively meet this challenge, a golden opportunity will pass to others and
      nutritional scientists will be left to follow them.

PMID- 11285345
TI  - AHA scientific statement: summary of the Scientific Conference on Dietary Fatty
      Acids and Cardiovascular Health. Conference summary from the Nutrition Committee
      of the American Heart Association.

PMID- 11285348
TI  - National nutrition and public health policies: issues related to bioavailability
      of nutrients when developing dietary reference intakes.
AB  - Dietary reference intakes (DRI), like its predecessor, the recommended dietary
      allowances (RDA) and the Recommended Nutrient Intakes (RNIs), are reference
      values, based on the best scientific evidence available. They serve as reference
      amounts of specific nutrients and food components for use in assessing the
      adequacy of and in planning for nutritious diets. They have been used for over 50
      y as the basis for national nutrition monitoring and intervention programs in the
      United States, Canada, and other countries and as the basis for dietary guidance
      developed for both individuals and for targeted groups of people. Thus, although
      not developed for specific policy applications, they have represented the best
      scientific perspectives regarding what should be the basis for nutrition and
      public health policy related to foods and supplements. In determining DRIs, as
      was the case with the RDA, significant attention must be paid to the form of the
      nutrient or food component that is evaluated. Research conducted to determine how
      much of a nutrient is needed must evaluate the chemical form provided, the matrix
      in which it is given and the effect of other food components on absorption and/or
      utilization. Because the DRI recommendations will be used in population-wide
      policy development, assumptions must be made explicitly about what is expected
      for all of these factors in a typical diet. At the same time, where data exist
      relative to nontypical but potentially very significant effects on
      bioavailability, these must also be delineated to be of use in a variety of
      settings. Finally, one of the most important aspects of determining
      bioavailability in developing reference intakes is that as new information
      emerges, new complexities enter into the process. As more chemical complexes of
      nutrients and food components become available in the marketplace, new
      bioavailability factors may need to be established. Examples of such changes
      exist in the DRI reports already published for vitamin B-12 and folate and in
      previous RDA for iron and protein. It is often the different assumptions related
      to bioavailability that alter the reference intakes used as the basis for public
      health policy in different countries, rather than the basic science from which
      the recommendation is derived.

PMID- 11285349
TI  - Using the national nutrition monitoring system to profile dietary supplement use.
AB  - The National Nutrition Monitoring and Related Research Program (NNMRRP) was
      defined by Congress in 1990 as "the set of activities necessary to provide timely
      information about the role and status of factors that bear on the contribution
      that nutrition makes to the health of the people of the United States" (7 U.S.C.
      section sign5302). The NNMRRP includes nearly 100 components at both the national
      and state level; the keystone components are the National Health and Nutrition
      Examination Surveys (conducted by the National Center for Health Statistics) and
      the Continuing Surveys of Food Intakes by Individuals (conducted by the
      Agricultural Research Service). These surveys were designed to measure
      individuals' consumption of foods and beverages and the nutrient intakes
      resulting from this consumption; expansion of these surveys to include dietary
      supplements and their nutrient contributions has been and continues to be a
      significant challenge. This article identifies the data needs regarding consumer
      use of dietary supplements in terms of the analytical demands to address the
      contribution dietary supplements make to "the health of the people of the United
      States." Important gaps in the data currently available are discussed. Current
      efforts to address dietary supplements are described along with recommendations
      regarding efficient use of the keystone surveys as well as other components of
      the NNMRRP.

PMID- 11285350
TI  - Dietary supplement use: consumer characteristics and interests.
AB  - Four major issues should be considered in a discussion of what consumers need to
      know about supplements and herbal treatments. 1) Usage of supplements is changing
      as consumers are taking charge of their health and seeking alternative forms of
      medicine (Eisenberg et al. 1998, Gilbert 1999 ). 2) The characteristics of
      supplement users have been profiled in numerous academic and industrial surveys.
      However, even the best models based on consumers' characteristics can predict <
      30% of diet-related behavior (Baranowski et al. 1999 ). 3) Experts in traditional
      medicine and nutrition lack information on supplements and herbals. The Practice
      and Policy Guidelines Panel of the National Institute of Health Office of
      Alternative Medicine (1997) stated that practices used in complementary and
      alternative medicine were "unsuitable for the development of evidence-based
      practice guidelines." Well-designed basic and clinical research is needed on the
      efficacy, bioavailability and safety of supplements and herbal medications. 4) It
      is debatable which agencies and professionals are the best gatekeepers of
      information on supplements and herbals. Significant numbers of consumers do not
      seem to rely on their physicians for information on alternative forms of medicine
      (Eisenberg 1997 ). Despite the obstacles, the traditional medical community
      (including nutritionists) should focus more research efforts on diet supplements
      and herbal treatments and increase training on these topics for students majoring
      in health care fields. Then health care professionals can mount high quality,
      targeted education programs for consumers.

PMID- 11285351
TI  - Factors influencing the measurement of bioavailability, taking calcium as a
      model.
AB  - For non-metabolizable supplemental nutrients, bioavailability is effectively
      equivalent to absorbability. Methods for measuring absorbability (balance,
      pharmacokinetic, tracer, urine increment, evoked physiological responses, and in
      vitro) are briefly characterized and their utility compared. When intrinsic
      labeling of a source is possible, tracer methods are generally the most accurate
      and precise, as well as often the least expensive. Factors influencing the
      measured end points of the various methods are described briefly. These include
      source factors such as pharmaceutic formulation, subject factors such as mucosal
      mass and the need status of the absorbing subject, and co-ingested factors such
      as other foods or food constituents. Extensive experience has shown that
      absorbability is difficult to predict from knowledge of the chemistry of the
      source, or even from the results of in vitro testing. Hence direct measurement of
      absorbability is essential to assure regulators and the general public that the
      source delivers what it promises.

PMID- 11285352
TI  - Bioavailability of nutrients: a practical approach to in vitro demonstration of
      the availability of nutrients in multivitamin-mineral combination products.
AB  - As the dietary supplements industry is registering steady and rapid growth,
      consumers are demanding quality supplements. Consumer perception of the quality
      of oral solid dosage forms is changing. Good quality is associated with the
      ability to disintegrate and dissolve. Performance characteristics of oral solid
      dosage forms in public standards will address the in vitro dissolution
      requirements, which will be presented as they relate to multivitamin-mineral
      combination products.

PMID- 11285353
TI  - Bioavailability of dietary supplements and impact of physiologic state: infants,
      children and adolescents.
AB  - Bioavailability can be broadly defined as the absorption and utilization of a
      nutrient, both of which may be affected by such host factors as gender,
      physiologic state and coexisting pathologic conditions. This report highlights
      factors of particular importance for the bioavailability of nutrients for
      infants, children and adolescents. Considerations for nutrient bioavailability
      for pediatric populations include maturation of the gastrointestinal tract,
      growth, character of the diet, and nutritional status. Critical periods of
      development include early infancy (0-6 mo), late infancy/early childhood (6-24
      mo) and adolescence (12-18 yr). Iron, zinc and calcium are minerals of particular
      interest and importance to pediatric populations and are susceptible to
      alterations in bioavailability. In the young infant, iron and zinc are highly
      bioavailable from human milk. By approximately 6 mo of age, other dietary sources
      are needed to maintain continued normal status. In breastfed infants who were
      born prematurely or with low birth weight, earlier supplemental iron is often
      recommended. For the older infant and toddler, iron and zinc are also important
      for normal growth and development. The bioavailability of these trace minerals in
      complementary foods is discussed. During adolescence, adequate calcium intake is
      critical to normal bone mineralization. In girls, peak calcium absorption and
      calcium deposition in bones occur at or near menarche, which illustrates the
      importance of the physiologic state on mineral bioavailability. Investigations
      into nutrient bioavailability must carefully consider these factors, because the
      failure to have well-matched comparison groups with respect to age and/or
      nutritional status may inadvertently mask differences in nutrient utilization.

PMID- 11285354
TI  - Effect of reproduction on the bioavailability of calcium, zinc and selenium.
AB  - Nutrient needs increase during pregnancy and lactation to support fetal growth
      and milk synthesis, respectively. Physiological adjustments that are made to meet
      those needs alter the fraction of ingested nutrient retained, or the
      bioavailability. Using stable isotopes as tracers, we measured calcium, zinc and
      selenium homeostasis in women during reproduction. The physiological response,
      and therefore the bioavailability, of these three minerals differed during
      reproduction. Calcium absorption increased approximately 2-fold during pregnancy
      but dropped to values for nonpregnant women during lactation. The calcium needs
      for lactation were met by renal conservation and bone resorption. In women
      chronically consuming a low calcium diet, fractional calcium absorption increased
      to >80% during reproduction. Zinc absorption tended to increase during pregnancy
      and lactation; renal conservation was not evident at any time during the
      reproductive cycle. Selenium absorption was high, approximately 80% of intake, in
      both pregnant and nonpregnant women. Pregnant women conserved selenium by
      decreasing urinary selenium excretion. Studies defining the impact of maternal
      status and the dietary mineral source and amount on mineral bioavailability are
      needed to determine the potential benefits of mineral supplementation during
      reproduction.

PMID- 11285355
TI  - Factors in aging that effect the bioavailability of nutrients.
AB  - Until a few years ago, little was known about bioavailability of micronutrients
      in elderly humans. It was assumed by many basic investigators and geriatricians
      that malabsorption of both macronutrients and micronutrients was a common problem
      among elderly persons. We now know that this is not the case; elderly persons who
      malabsorb macronutrients do so because of disease, not because of age. This
      report will be divided into three sections. The first section focuses on the
      general principles of absorptive processes in elderly persons. The second section
      focuses on the bioavailability of specific micronutrients in elderly persons,
      with specific examples of "problem" nutrients. The third section lays out a
      proposed research agenda for studying the bioavailability of nutrients and other
      active components of dietary supplements in elderly persons.

PMID- 11285356
TI  - Bioavailability of pure isoflavones in healthy humans and analysis of commercial
      soy isoflavone supplements.
AB  - The pharmacokinetic behavior of naturally occurring isoflavones has been
      determined for the first time in healthy adults. We compared plasma kinetics of
      pure daidzein, genistein and their beta-glycosides administered as a single-bolus
      dose to 19 healthy women. This study demonstrates differences in the
      pharmacokinetics of isoflavone glycosides compared with their respective beta
      glycosides. Although all isoflavones are efficiently absorbed from the intestinal
      tract, there are striking differences in the fate of aglycones and beta
      glycosides. Mean time to attain peak plasma concentrations (t(max)) for the
      aglycones genistein and daidzein was 5.2 and 6.6 h, respectively, whereas for the
      corresponding beta-glycosides, the t(max) was delayed to 9.3 and 9.0 h,
      respectively, consistent with the residence time needed for hydrolytic cleavage
      of the glycoside moiety for bioavailability. The apparent volume of distribution
      of isoflavones confirms extensive tissue distribution after absorption. Plasma
      genistein concentrations are consistently higher than daidzein when equal amounts
      of the two isoflavones are administered, and this is accounted for by the more
      extensive distribution of daidzein (236 L) compared with genistein (161 L). The
      systemic bioavailability of genistein [mean AUC = 4.54 microg/(mL x h)] is much
      greater than that of daidzein [mean AUC = 2.94 microg/(mL x h)], and
      bioavailability of these isoflavones is greater when ingested as beta-glycosides
      rather than aglycones as measured from the area under the curve of the plasma
      appearance and disappearance concentrations. The pharmacokinetics of methoxylated
      isoflavones show distinct differences depending on the position of the methoxyl
      group in the molecule. Glycitin, found in two phytoestrogen supplements,
      underwent hydrolysis of the beta-glycoside moiety and little further
      biotransformation, leading to high plasma glycitein concentrations. Biochanin A
      and formononetin, two isoflavones found in one phytoestrogen supplement, were
      rapidly and efficiently demethylated, resulting in high plasma genistein and
      daidzein concentrations typically observed after the ingestion of soy-containing
      foods. These differences in pharmacokinetics and metabolism have implications for
      clinical studies because it cannot be assumed that all isoflavones are comparable
      in their pharmacokinetics and bioavailability. An analysis of 33 phytoestrogen
      supplements and extracts revealed considerable differences in the isoflavone
      content from that claimed by the manufacturers. Plasma concentrations of
      isoflavones show marked qualitative and quantitative differences depending on the
      type of supplement ingested. These studies indicate a need for improvement in
      quality assurance and standardization of such products.

PMID- 11285357
TI  - Case study: folate bioavailability.
AB  - Folate nutritional status depends on intake from food and supplements as well as
      on the bioavailability of the various ingested forms of this vitamin. Although
      many advances in the understanding of folate bioavailability have occurred in
      recent years, many areas of uncertainty remain, especially with respect to
      naturally occurring dietary folate. This review includes a summary of factors
      that affect folate absorption and utilization, currently used and promising
      methods suitable for the assessment of bioavailability, significant findings on
      which current understanding is based and research needs.

PMID- 11285358
TI  - Iron.
AB  - The most useful and appropriate methods for assessing the bioavailability of
      (nonheme) iron supplements are described. When the supplement can be labeled
      isotopically, the best method for measuring bioavailability is hemoglobin
      incorporation, followed by fecal monitoring. Caco-2 cell in vitro systems can be
      used for rapid screening to predict potential availability for absorption. If the
      compound cannot be labeled, then the plasma appearance/disappearance of oral iron
      given together with an intravenous dose of iron isotope can be used to quantify
      absorption. With oral doses in excess of 25 mg, the 4- to 6-h plasma
      concentration can provide a qualitative assessment of bioavailability. Approaches
      for normalizing results to minimize intraindividual and interindividual
      variability in efficiency of iron absorption are discussed.

PMID- 11285359
TI  - What do we need to know about active ingredients in dietary supplements? Summary
      of workshop discussion.

PMID- 11285360
TI  - The impact of formulation on bioavailability: summary of workshop discussion.

PMID- 11285361
TI  - What impact does stage of physiological development and/or physiological state
      have on the bioavailability of dietary supplements? Summary of workshop
      discussion.

PMID- 11285362
TI  - Methodological issues in assessing bioavailability of nutrients and other
      bioactive substances in dietary supplements: summary of workshop discussion.

PMID- 11285363
TI  - How can we best communicate our understanding of the elements of bioavailability
      to the consuming public? Summary of workshop discussion.

PMID- 11285364
TI  - Genetic variation in mRNA coding sequences of highly conserved genes.
AB  - The frequency and distribution of genetic polymorphism in the human genome is a
      question of major importance. We have studied this in highly conserved genes,
      which encode crucial functions such as DNA replication, mRNA transcription, and
      translation. Evolutionary comparisons suggest that these genes are under
      particularly strong selective pressure, and their frequency of nucleotide
      sequence polymorphism would be expected to represent a minimum estimate for
      sequence variation throughout the genome. We have analyzed the complete coding
      sequence and the 3'-untranslated region (3'-UTR) of 22 human genes, most of which
      have homologs in all cellular organisms and all of which are at least 25% amino
      acid identical to homologs in yeast. Comparisons with similar studies of less
      conserved human disease genes indicate that 1) evolutionarily conserved genes
      are, on average, less polymorphic than disease related genes; 2) the difference
      in polymorphism levels is attributable almost entirely to reduced levels of
      variation in protein coding sequences, whereas noncoding sequences have similar
      levels of polymorphism; and 3) the character of polymorphism, in terms of the
      spectrum and frequency of mutational changes, is similar.

PMID- 11285365
TI  - VHL tumor suppressor regulates Cl-/HCO3- exchange and Na+/H+ exchange activities
      in renal carcinoma cells.
AB  - Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are thought to
      play a critical role in the pathogenesis of both sporadic and VHL disease
      associated clear-cell renal carcinomas (RCC). Differential display-PCR identified
      the AE2 anion exchanger as a candidate VHL target gene. AE2 mRNA and polypeptide
      levels were approximately threefold higher in 786-O VHL cells than in 786-O Neo
      cells. In contrast, Cl(-)/HCO(3)(-) exchange activity in 786-O VHL cells was 50%
      lower than in 786-O Neo cells. Since resting intracellular pH (pH(i)) values were
      indistinguishable, we postulated that Na(+)/H(+) exchange activity (NHE) might be
      similarly reduced in 786-O VHL cells. NHE-mediated pH(i) recovery from acid load
      was less than 50% that in 786-O Neo cells, whereas hypertonicity-stimulated,
      amiloride-sensitive NHE was indistinguishable in the two cell lines. The NHE3
      mRNA level was higher in 786-O VHL than 786-O Neo cells, but NHE1 mRNA levels did
      not differ. AE2 and NHE3 are the first transcripts reported to be upregulated by
      pVHL. Elucidation of mechanisms responsible for downregulation of both ion
      exchange activities will require further investigation.

PMID- 11285366
TI  - Insights into a plasma membrane signature.
AB  - The plasma membrane (PM) is an organized biological system that serves as a
      structural barrier and communication interface with the extracellular
      environment. Many basic questions regarding the PM as a system remain unanswered.
      In particular, we do not understand the scope of similarity and differences in
      protein expression at the PM. This study takes an initial step toward addressing
      these questions by comparing the PM proteomes of fibroblasts and mammary
      carcinoma cells. Three sets of proteins were revealed by the study. The first set
      comprises between 9 and 23% of all proteins at the PM and appears to be common to
      both fibroblasts and mammary carcinoma. A second group of proteins, comprising
      approximately 40% of the proteins at the PM, is tightly linked to cell lineage.
      The third set of proteins is unique to each cell line and is independent of cell
      lineage. It is reasonable to hypothesize then, that this third group of proteins
      is responsible for unique aspects of cell behavior. In an effort to find proteins
      linked to the metastatic phenotype, we identified several proteins that are
      uniquely expressed at the PM of the metastatic MDA-MB-435 cells. These proteins
      have functions ranging from cell adhesion to the regulation of translation and
      the control of oxidant stress.

PMID- 11285368
TI  - Time course of LPS-induced gene expression in a mouse model of genitourinary
      inflammation.
AB  - In this study, self-organizing map (SOM) gene cluster techniques are applied to
      the analysis of cDNA microarray analysis of gene expression changes occurring in
      the early stages of genitourinary inflammation. We determined the time course of
      lipopolysaccharide (LPS)-induced gene expression in experimental cystitis. Mice
      were euthanized 0.5, 1, 4, and 24 h after LPS instillation into the urinary
      bladder, and gene expression was determined using four replicate Atlas mouse cDNA
      expression arrays containing 588 known genes at each time point. SOM gene cluster
      analysis, performed without preconditions, identified functionally significant
      gene clusters based on the kinetics of change in gene expression. Genes were
      classified as follows: 1) expressed at time 0; 2) early genes (peak expression
      between 0.5 and 1 h); and 3) late genes (peak expression between 4 and 24 h). One
      gene cluster maintained a constant level of expression during the entire time
      period studied. In contrast, LPS treatment downregulated the expression of some
      genes expressed at time 0, in a cluster including transcription factors,
      protooncogenes, apoptosis-related proteins (cysteine protease), intracellular
      kinases, and growth factors. Gene upregulation in response to LPS was observed as
      early as 0.5 h in a cluster including the interleukin-6 (IL-6) receptor, alpha-
      and beta-nerve growth factor (alpha- and beta-NGF), vascular endothelial growth
      factor receptor-1 (VEGF R1), C-C chemokine receptor, and P-selectin. Another
      tight cluster of genes with marked expression at 1 h after LPS and insignificant
      expression at all other time points studied included the protooncogenes c-Fos,
      Fos-B, Fra-2, Jun-B, Jun-D, and Egr-1. Almost all interleukin genes were
      upregulated as early as 1 h after stimulation with LPS. Nuclear factor-kappaB (NF
      kappaB) pathway genes collected in a single cluster with a peak expression 4 h
      after LPS stimulation. In contrast, most of the interleukin receptors and
      chemokine receptors presented a late peak of expression 24 h after LPS coinciding
      with the peak of neutrophil infiltration into the bladder wall. Selected cDNA
      microarray observations were confirmed by RNase protection assay. In conclusion,
      the cDNA array experimental approach provided a global profile of gene expression
      changes in bladder tissue after stimulation with LPS. SOM techniques identified
      functionally significant gene clusters, providing a powerful technical basis for
      future analysis of mechanisms of bladder inflammation.

PMID- 11285369
TI  - Psoriatic arthritis--emerging concepts.

PMID- 11285367
TI  - Cloning and functional characterization of an uncoupling protein homolog in
      hummingbirds.
AB  - The cDNA of an uncoupling protein (UCP) homolog has been cloned from the swallow
      tailed hummingbird, Eupetomena macroura. The hummingbird uncoupling protein
      (HmUCP) cDNA was amplified from pectoral muscle (flight muscle) using RT-PCR and
      primers for conserved domains of various known UCP homologs. The rapid
      amplification of cDNA ends (RACE) method was used to complete the cloning of the
      5' and 3' ends of the open reading frame. The HmUCP coding region contains 915
      nucleotides, and the deduced protein sequence consists of 304 amino acids, being
      approximately 72, 70, and 55% identical to human UCP3, UCP2, and UCP1,
      respectively. The uncoupling activity of this novel protein was characterized in
      yeast. In this expression system, the 12CA5-tagged HmUCP fusion protein was
      detected by Western blot in the enriched mitochondrial fraction. Similarly to rat
      UCP1, HmUCP decreased the mitochondrial membrane potential as measured in whole
      yeast by uptake of the fluorescent potential-sensitive dye 3',3
      dihexyloxacarbocyanine iodide. The HmUCP mRNA is primarily expressed in skeletal
      muscle, but high levels can also be detected in heart and liver, as assessed by
      Northern blot analysis. Lowering the room's temperature to 12-14 degrees C
      triggered the cycle torpor/rewarming, typical of hummingbirds. Both in the
      pectoral muscle and heart, HmUCP mRNA levels were 1.5- to 3.4-fold higher during
      torpor. In conclusion, this is the first report of an UCP homolog in birds. The
      data indicate that HmUCP has the potential to function as an UCP and could play a
      thermogenic role during rewarming.

PMID- 11285371
TI  - Increased cell proliferation and associated expression of PDGFRbeta causing
      hypercellularity in patellar tendinosis.
AB  - OBJECTIVE: This study assessed cellularity in patellar tendinosis with respect to
      cell proliferation and the expression of platelet-derived growth factor receptor
      beta (PDGFRbeta). METHODS: Surgical samples were taken from 11 patients
      fulfilling criteria of patellar tendinosis and from 12 matched controls. Standard
      immunohistochemistry methods were used to detect expression of PDGFRbeta and
      proliferation cell nuclear antigen (PCNA). Results were analysed by computer
      assisted microscopy. Tendon cells were isolated from nine tendinosis and eight
      control tissues for cell culture. RESULTS: Increased cellularity (P<0.001) was
      observed in tendinosis tissues compared with controls, and also a higher
      proliferative index (P:<0.001). Increased expression of PDGFRbeta was
      demonstrated (P<0.001). Cultured tendinosis cells showed a higher proliferation
      rate than controls (P<0.001). This was maintained when the cells were cultured
      under various conditions of serum supplementation (P<0.01). Tendinosis cells also
      showed a higher proliferation rate (P<0.01) in medium containing 10 ng/ml PDGF.
      CONCLUSION: Hypercellularity in patellar tendinosis is caused by increased cell
      proliferation and is associated with increased expression of PDGFRbeta.

PMID- 11285372
TI  - A case-control study examining the role of physical trauma in the onset of
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether physical trauma may precipitate the onset of
      rheumatoid arthritis (RA). METHOD: In a case-control study comparing RA out
      patients with controls attending non-rheumatology out-patient clinics, 262
      patients and 262 age- and sex-matched controls completed a postal questionnaire
      or were interviewed about any physical trauma in the 6 months before the onset of
      their symptoms. RESULTS: Fifty-five (21%) of the RA patients reported significant
      physical trauma in the 6 months before the onset of their disease, compared with
      only 17 (6.5%) of the controls (P<0.00001). A preceding history of physical
      trauma was significantly more common in RA patients who were seronegative for
      rheumatoid factor (P=0.03), but was not significantly associated with sex
      (P=0.78), age (P=0.64), a family history of RA (P=0.07) or type of occupation,
      defined as manual or sedentary (P=0.6). CONCLUSION: Physical trauma in the
      preceding 6 months is significantly associated with the onset of RA.

PMID- 11285370
TI  - Expression of proteinases and inflammatory cytokines in subchondral bone regions
      in the destructive joint of rheumatoid arthritis.
AB  - OBJECTIVE: We previously described abnormalities in the bone marrow of patients
      with rheumatoid arthritis (RA), but were able to shed little light on the
      pathogenic roles of inflammatory cytokines and proteinases in joint destruction
      in the subchondral region in RA. This is the first report to describe the co
      localization of cytokines and proteinases in this area. METHODS: Decalcified
      paraffin-embedded sections from 10 patients with RA and five patients with
      osteoarthritis (OA) were examined for the immunolocalization of cathepsins B, K
      and L and the localization of messenger RNAs for interleukin 1beta (IL-1beta),
      tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 9 (MMP-9).
      The cells were double-stained with anti-CD68 or anti-prolyl 4-hydroxylase (PH)
      antibody. RESULTS: An immunohistochemical study confirmed the expression of
      cathepsins B and L by CD68-positive mononuclear cells at the sites of significant
      cartilage and bone erosion from the subchondral region in all RA specimens.
      Osteoclast-like cells showed intense staining for cathepsin K and MMP-9.
      Osteoblast-like cells strongly expressed MMP-9. Analysis of serial sections
      revealed that expression of the IL-1beta and TNF-alpha genes occurred near that
      of the cathepsins and MMP-9 in the subchondral region. CONCLUSION: We conclude
      that inflammatory cytokines and tissue-damaging proteinases play important roles
      in joint destruction in the subchondral region in RA.

PMID- 11285374
TI  - The relationship of the compressive modulus of articular cartilage with its
      deformation response to cyclic loading: does cartilage optimize its modulus so as
      to minimize the strains arising in it due to the prevalent loading regime?
AB  - AIM: To investigate the relationship of the instantaneous compressive modulus
      with its deformation response to cyclic loading typical of that encountered at
      the knee joint during level walking. METHOD: The study was performed on 24
      osteochondral plugs taken from three unembalmed cadaveric knees. As the
      compressive modulus of cartilage has been shown to vary topographically across
      the knee in an established manner, the specimens were taken from specific sites
      on the femur and tibia of each knee. All the cartilage specimens were immersed in
      Hanks' salt solution at 37 degrees C and were subjected to the same cyclic
      loading regimen that was representative of a typical walking cycle in a
      specialized indentation apparatus, for over 1 h. RESULTS AND CONCLUSION: The
      viscous and elastic components of matrix strain, the creep rate and the cartilage
      compressive modulus were measured. The latter was found to be significantly
      related to the strain response of cartilage to cyclic loading. Elastic strain
      varied exponentially with the compressive modulus; specimens with a modulus less
      than 4 MPa experienced elastic strains in the range 0.18-0.36, whereas stiffer
      specimens experienced strains between 0.05 and 0.13. Viscous strain varied
      linearly with cartilage stiffness and was as low as 0.02 at the lower values of
      the compressive modulus but increased to 0.22 for a compressive modulus of 18
      MN/m(2). The rate of creep under cyclic load was inversely linearly related to
      cartilage stiffness. The strain response of soft specimens approached steady
      state by 200 cycles but that of stiff specimens did not approach it until 1300
      cycles. It was hypothesized that the viscous strain response of cartilage can be
      explained in terms of differences in permeability between specimens of different
      compressive modulus, stiffer cartilage having a lower permeability than soft
      cartilage.

PMID- 11285373
TI  - Glucocorticoid-mediated repression of inflammatory cytokine production in
      fibroblast-like rheumatoid synoviocytes is independent of nuclear factor-kappaB
      activation induced by tumour necrosis factor alpha.
AB  - OBJECTIVE: To determine whether steroids inhibit the production of inflammatory
      cytokines by the inhibition of nuclear factor kappaB (NF-kappaB) activation in
      fibroblast-like rheumatoid synoviocytes (FLSs) under inflammatory conditions, and
      to determine whether steroids stimulate the induction of synthesis of the
      inhibitory protein IkappaB-alpha in the anti-inflammatory immune response of
      these cells. METHODS: Expression of the interleukin-6 (IL-6) and interleukin
      1beta (IL-1beta) genes was measured by semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR), and the secreted IL-6 was measured with the
      enzyme-linked immunosorbent assay. Inhibition of the NF-kappaB activation was
      examined with the electrophoretic mobility shift assay (EMSA). In order to study
      dexamethasone (DEX)-dependent regulation of IkappaB-alpha expression, we
      performed Western blotting before and after stimulation with tumour necrosis
      factor alpha (TNF-alpha). RESULTS: The inflammatory cytokine study showed that
      DEX suppressed gene expression and the production of protein in FLSs. EMSA
      demonstrated that identical amounts of NF-kappaB were present in the nucleus of
      the FLSs stimulated by TNF-alpha, with or without pretreatment with DEX.
      Treatment of FLSs with DEX did not induce an increase in IkappaB-alpha sufficient
      to prevent nuclear translocation of NF-kappaB on stimulation with TNF-alpha.
      CONCLUSION: DEX may suppress the production of inflammatory cytokines, such as IL
      6 and IL-1beta, but it neither prevents the translocation of NF-kappaB to the
      nucleus nor induces the synthesis of IkappaB-alpha protein in FLSs stimulated by
      TNF-alpha.

PMID- 11285375
TI  - Knee bracing for medial compartment osteoarthritis: effects on proprioception and
      postural control.
AB  - OBJECTIVE: To evaluate the effects of a functional knee brace specifically
      designed for patients with varus gonarthrosis on measures of proprioception and
      postural control. SUBJECTS: Fourteen men and six women (aged 59+/-9 yr) with
      measurable varus alignment and osteoarthritis of the knee medial compartment.
      METHODS: Proprioception was assessed in the sitting position using an isokinetic
      dynamometer and was quantified as the ability to replicate target knee-joint
      angles. Postural control was assessed with a force platform using tests of single
      limb standing balance performed, while the patient was standing on a stable
      surface and standing on foam, and was quantified as the total length of the path
      of the centre of pressure. All tests were performed with and without the
      patient's own custom-fit valgus brace. RESULTS: Proprioception was significantly
      improved following application of the brace [mean difference=0.7 degrees, 95%
      confidence interval (CI)=0.2 to 1.1 degrees ). Postural control was not
      significantly affected by the use of the brace during the stable surface test
      (mean difference=2.6 cm, 95% CI=-4.3 to 9.5 cm) or the foam surface test (mean
      difference=0.9 cm, 95% CI=-7.5 to 9.4 cm). CONCLUSION: Although enhanced
      proprioception may be partially responsible for reported improvements with the
      use of a brace, the present findings call into question the functional importance
      of the small changes observed.

PMID- 11285376
TI  - Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin
      and [3H]imipramine reuptake in the primary fibromyalgia syndrome.
AB  - BACKGROUND: Primary fibromyalgia syndrome (PFS) is a chronic disorder commonly
      seen in rheumatological practice. The pathophysiological disturbances of this
      syndrome, which was defined by the American College of Rheumatology in 1990, are
      poorly understood. This study evaluated, in 30 patients, the hypothesis that PFS
      is a pain modulation disorder induced by deregulation of serotonin metabolism.
      OBJECTIVES: To compare platelet [(3)H]imipramine binding sites and serotonin (5
      HT) levels in plasma-rich platelets (PRP) of PFS patients with those of matched
      healthy controls and to compare the levels of biogenic amine metabolites in the
      cerebrospinal fluid (CSF) of PFS patients with those of matched controls.
      METHODS: Platelet [(3)H]imipramine binding sites were defined by two criteria,
      B(max) for their density and K(d) for their affinity. PRP 5-HT and CSF
      metabolites of 5-HT (5-hydroxyindoleacetic acid, 5-HIAA), norepinephrine (3
      methoxy, 4-hydroxy phenylglycol, MHPG) and dopamine (homovanillic acid, HVA) were
      assayed by reversed-phase high-performance liquid chromatography with coulometric
      detection. RESULTS: [(3)H]Imipramine platelet binding was similar (P=0.43 for
      B(max) and P=0.30 for K(d)) in PFS patients (B(max)=901+/-83 fmol/mg protein,
      K(d)=0.682+/-0.046) and in matched controls (B(max)=1017+/-119 fmol/mg protein,
      K(d)=0.606+/-0.056). PRP 5-HT was significantly higher (P=0.0009) in PFS patients
      (955+/-101 ng/10(9) platelets) than in controls (633+/-50 ng/10(9) platelets).
      When adjusted for age, the levels of all CSF metabolites were lower in PFS
      patients. The CSF metabolite of norepinephrine (MHPG) was lower (P:=0.003) in PFS
      patients (8.33+/-0.33 ng/ml) than in matched controls (9.89+/-0.31 ng/ml) and 5
      HIAA was lower (P=0.042) in PFS female patients (22.34+/-1.78 ng/ml) than in
      matched controls (25.75+/-1.75 ng/ml). For HVA in females, the difference between
      PFS patients (36.32+/-3.20 ng/ml) and matched controls (38.32+/-2.90 ng/ml)
      approached statistical significance (P=0.054). CONCLUSION: Changes in metabolites
      of CSF biogenic amines appear to be partially correlated to age but remained
      diagnosis-dependent. High levels of PRP 5-HT in PFS patients were associated with
      low CSF 5-HIAA levels in female patients but were not accompanied by any change
      in serotonergic uptake as assessed by platelet [(3)H]imipramine binding sites.
      These findings do not allow us to confirm that serotonin metabolism is
      deregulated in PFS patients.

PMID- 11285377
TI  - The relationship between soft tissue swelling, joint space narrowing and erosive
      damage in hand X-rays of patients with rheumatoid arthritis.
AB  - OBJECTIVES: To test the hypotheses that the progression of joint space narrowing
      behaves differently from the progression of erosions and that clinically and
      radiologically assessed soft tissue swelling relates more to diffuse cartilage
      loss than to erosive damage. METHODS: Radiographs and clinical data were obtained
      from 28 patients in a prospective, multicentre, randomized, placebo-controlled
      trial of prednisolone 7.5 mg daily over 2 yr. Radiographic scoring included the
      Larsen score, joint space narrowing and soft tissue swelling. Clinical joint
      inflammation in the hands was assessed every 3 months and cumulative synovitis
      score over the period of study was then calculated for each joint. The placebo
      treated patients and the prednisolone-treated patients were analysed separately.
      The Larsen scores were compared after log transformation [transformed
      score=log(10) (original score+1)]. Changes in Larsen scores and joint space
      narrowing scores were compared with the cumulative presence of clinical synovitis
      and radiological soft tissue swelling using the correlation coefficient. RESULTS:
      There was a difference in the rate of progression in the Larsen score between
      placebo- and prednisolone-treated patients, but there was no significant
      difference in the rate of joint space loss. In placebo-treated patients, measures
      of synovitis correlated more strongly with progression of joint space narrowing
      than with changes in the Larsen score. In prednisolone-treated patients there was
      no correlation between clinical synovitis and change in Larsen score (r=0.029)
      and only a slight and non-significant correlation with joint space narrowing
      (r=0.127). Radiographic evidence of soft tissue swelling remained correlated with
      joint space narrowing (r=0.279, P:<0.001) but was not correlated with change in
      Larsen score (r=-0.113, P:<0.001 for difference between correlations). The
      correlation between Larsen score progression and joint space narrowing seen in
      the non-treated patients was completely abolished in the glucocorticoid-treated
      group (r=-0.003). CONCLUSIONS: The progression of joint space narrowing behaves
      differently from the progression of erosions. Prednisolone slows (or even stops)
      the progression of erosions (as assessed by the Larsen score) while making no
      difference to the progression of cartilage loss (as assessed by joint space
      narrowing). The results also suggest that synovitis, whether measured clinically
      or radiologically, is more closely related to diffuse cartilage loss than to
      erosion progression. Any link between synovitis and erosions is abolished by
      glucocorticoid therapy while the link between synovitis and cartilage loss is
      not, pointing to at least two different mechanisms for these observed
      radiological features.

PMID- 11285378
TI  - Expression of interleukin-18 and its monokine-directed function in rheumatoid
      arthritis.
AB  - OBJECTIVES: To investigate the expression of and monokine induction by
      interleukin 18 (IL-18; also called interferon-gamma inducing factor, IGIF), in
      peripheral blood mononuclear cells (PBMC) and cultured synoviocytes from
      rheumatoid arthritis (RA) patients. METHODS: We carried out IL-18 Western
      blotting and semi-quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) of cytokines in PBMC [IL-18, IL-1beta and tumour necrosis factor alpha
      (TNF-alpha)] and long-term cultured fibroblast-like synoviocytes (FLS) [IL-18, IL
      1beta, TNF-alpha, IL-6, interferon gamma (INF-gamma) and [granulocyte-macrophage
      colony stimulating factor (GM-CSF)] from RA patients and controls. FLS were
      isolated from RA synovial membranes (FLS(SM)) and RA synovial fluids (FLS(SF)),
      osteoarthritis (OA) FLS(SM) and FLS(SF) from spondyloarthropathy patients. FLS
      were characterized by fluorescence-activated cell sorting of the FLS. PBMC and
      FLS from RA patients and control subjects were stimulated with recombinant human
      IL-18 and IL-1beta (rHuIL-18/rHuIL-1beta), and TNF-alpha, IL-1beta and MMP-1 were
      measured by ELISA in supernatants. RESULTS: Constitutive expression of IL-18 mRNA
      was significantly reduced whereas that of TNF-alpha was enhanced in RA PBMC.
      Persistent low expression of IL-18, TNF-alpha, GM-CSF and IL-1beta was observed
      in RA and OA FLS(SM) as well as spondyloarthropathy FLS(SF). In contrast, high
      constitutive expression of IL-18 in FLS (CD90/Thy-1- and CD54-positive, CD14- and
      CD86-negative), accompanied by persistent high levels of TNF-alpha, GM-CSF and IL
      1beta expression, was restricted to synovial fluid-derived FLS obtained from RA
      patients. IFN-gamma was not detectable in any culture, but IL-6 mRNA was equally
      expressed in all FLS cultures. rHuIL-18 was effective in stimulating TNF-alpha
      and IL-1beta secretion in PBMC from healthy controls, but failed to stimulate TNF
      alpha and IL-1beta secretion from PBMC in 11 of 12 RA patients, and all FLS
      cultures. rHu-IL-1beta, but not rHu-IL-18, induced interstitial collagenase (MMP
      1) in FLS. CONCLUSIONS: Persistent high production of proinflammatory cytokines
      in RA-FLS(SF) may be relevant for chronic progression in RA synovitis. Levels of
      TNF-alpha and IL-1beta expression are increased in RA-FLS(SF), but are
      independent of IL-18. The pathological function of enhanced IL-18 expression in
      RA-FLS(SF) remains to be further elucidated.

PMID- 11285379
TI  - Assessment of pituitary gonadotropin release to gonadotropin releasing
      hormone/thyroid-stimulating hormone stimulation in women with systemic sclerosis.
AB  - OBJECTIVE: To evaluate basal and dynamic levels of pituitary gonadotropin release
      in female systemic sclerosis (SSc) patients of childbearing age and in post
      menopausal SSc patients. METHODS: We performed stimulation tests for gonadotropin
      releasing hormone (GnRH) and thyroid-stimulating hormone (TRH) during the early
      follicular phase in 12 women of childbearing age [mean age (S.E.M.) 34.8 (2.4)
      yr] with SSc to determine serum concentrations of follicle-stimulating hormone
      (FSH), luteinizing hormone (LH) and prolactin. Blood samples were also obtained
      from six post-menopausal women with SSc [mean age 46.8 (2.4) yr], after TRH
      stimulation; only serum prolactin concentration was determined, because elevated
      basal concentrations of FSH and LH were expected. Hormone concentrations were
      estimated by radioimmunoassay. Comparisons were made with healthy control women
      matched for age and reproductive status. RESULTS: In SSc patients of childbearing
      age, basal FSH, LH and oestradiol (E(2)) levels were not significantly different
      from those in controls, whereas basal prolactin concentration was significantly
      higher than in controls (P=0.0001). After the stimulation test, the peak
      concentrations of FSH (P=0.0001) and prolactin (P<0.0001) were significantly
      higher than in controls. The net integrated response curves [net area under the
      curve (AUC)] for FSH and LH did not differ significantly between SSc patients and
      controls. On the contrary, the net AUC for prolactin in response to TRH
      stimulation was significantly higher than in controls (P=0.001). In post
      menopausal patients, basal E(2), FSH, LH and prolactin levels were not
      significantly different between women with SSc and controls. However, after TRH
      stimulation, peak levels and net AUC for prolactin were not significantly higher
      in patients than those in controls. No significant correlations were found
      between basal and stimulated FSH, LH and prolactin levels and the severity of
      involvement of various organ systems. Multiple regression analysis showed that
      basal and stimulated prolactin concentrations were associated with skin sclerosis
      and peripheral vascular and lung involvement. CONCLUSION: Our results suggest
      that subclinical primary hypogonadism can occur in SSc patients. They also
      confirm an alteration in the mechanism for prolactin secretion and release, which
      may not only contribute to further disturbance of the reproductive axis but may
      also have an influence on the disease.

PMID- 11285380
TI  - Urinary excretion of glucosyl-galactosyl pyridinoline: a specific biochemical
      marker of synovium degradation.
AB  - OBJECTIVE: Glucosyl-galactosyl pyridinoline (Glc-Gal-PYD), which has been
      identified in urine, is a glycosylated analogue of pyridinoline. The tissue
      distribution of this molecule has not been yet determined and its utility as a
      potential biochemical marker of joint degradation in patients with joint diseases
      has not been investigated. METHODS AND RESULTS: In this study, we demonstrate
      that Glc-Gal-PYD is abundant in human synovium tissue, absent from bone and
      present in minute amounts in cartilage and other soft tissues, such as muscle and
      liver. Using an ex vivo model of human joint tissue degradation, we found that
      Glc-Gal-PYD is released from synovium tissue, but not from bone and cartilage.
      The urinary level of Glc-Gal-PYD was increased by 109% in patients with
      rheumatoid arthritis (RA) compared with healthy adults, but was normal in
      patients with Paget's disease of bone. In addition, Glc-Gal-PYD was higher in
      those patients with destructive disease, as assessed by X-rays of the joints,
      than in those with non-destructive RA. CONCLUSION: Glc-Gal-PYD may be useful for
      the clinical investigation of patients with joint disease.

PMID- 11285381
TI  - Chromium-51 ethylenediamine tetraacetic acid glomerular filtration rate: a better
      predictor than glomerular filtration rate calculated by the Cockcroft-Gault
      formula for renal involvement in systemic lupus erythematosus patients.
AB  - OBJECTIVE: To investigate whether the ethylenediamine tetraacetic acid (EDTA)
      glomerular filtration rate (GFR) is a better indicator of the degree of renal
      involvement than serum creatinine concentration or creatinine clearance
      calculated by the Cockroft-Gault formula. METHODS: We studied prospectively all
      systemic lupus erythematosus (SLE) patients with normal or borderline serum
      creatinine concentration (<110 micromol/l) and urinary sediment abnormalities
      and/or proteinuria in the last 2 yr. EDTA-GFR, serum creatinine concentration,
      calculated creatinine clearance (Cockroft-Gault formula) and 24-h urine protein
      were determined at the same time. Renal biopsies were performed in patients with
      low values of EDTA-GFR or significant proteinuria. RESULTS: Twenty-three patients
      were identified, of whom 22 were females. The average age of the patients was
      31.6+/-8.2 yr. Biopsies were assigned to WHO classes as follows: class II, 1
      patient; class III, 6 patients; class IV, 10 patients; class V, 6 patients. The
      average serum creatinine concentration, EDTA-GFR and calculated creatinine
      clearance were 79.8+/-mol/l, 74.5 ml/min and 97 ml/min respectively. EDTA-GFR
      showed abnormal values (<80 ml/min) in 15 of the 23 patients (65.2%) while
      calculated creatinine clearance was abnormal (<80 ml/min) in three of the 23
      patients (13%) (P<0.001). Using the Pearson correlation test, we did not find any
      correlation between EDTA-GFR or creatinine clearance values and the sum of
      activity and chronicity indices. CONCLUSION: GFR performed by EDTA-GFR correctly
      predicted renal involvement in SLE patients, whereas GFR calculated by the
      Cockcroft-Gault formula may have underestimated renal function. Significant
      numbers of patients with WHO class III, IV or V lupus nephritis may be missed if
      biochemical creatinine clearance or serum creatinine concentration alone is used
      to assess renal disease.

PMID- 11285382
TI  - Minocycline-induced lupus: clinical features and response to rechallenge.
AB  - OBJECTIVE: To describe the spectrum of clinical features in patients with
      minocycline-induced lupus (MIL) and determine their response to rechallenge.
      METHODS: The clinical features and laboratory findings of 23 patients with MIL
      were recorded. Ten patients were rechallenged, and their C-reactive protein (CRP)
      levels were monitored. RESULTS: All subjects complained of polyarthralgia; three
      had metacarpophalangeal and proximal interphalangeal joint synovitis and one had
      bilateral knee effusions. Elevated hepatic transaminases were noted in eight
      subjects. Cutaneous vasculitis was a feature in two cases. None had renal or
      central nervous system disease, although five patients complained of impaired
      concentration and poor memory and a single patient had a peripheral sensory
      neuropathy. The following serological abnormalities were detected: antinuclear
      antibodies (19/23 patients); antibodies to double-stranded DNA (4/23);
      perinuclear antineutrophil cytoplasmic antibodies (10/15); IgG anti-cardiolipin
      antibodies (6/23); hypergammaglobulinaemia (12/19). Anti-histone antibodies were
      negative in 9/9 cases. Rechallenge resulted in rapid recurrence of symptoms and
      elevation of CRP levels. CONCLUSION: MIL is associated with a wide spectrum of
      clinical and serological features. The diagnosis can be confirmed by rechallenge,
      which results in rapid reappearance of symptoms and a rise in CRP.

PMID- 11285383
TI  - The role of hyaluronic acid in protecting surface-active phospholipids from lysis
      by exogenous phospholipase A(2).
AB  - BACKGROUND: This in vitro study aimed to elucidate the extent and kind of
      involvement of hyaluronic acid (HA) in the currently accepted view of synovial
      joint lubrication, in which surface-active phospholipids (SAPL) constitute the
      main boundary lubricant. The integrity of SAPL is apparently threatened by the
      lysing activity of phospholipase A(2) (PLA(2)). METHODS: The effects of
      increasing concentrations of HA degraded by free radicals and non-degraded HA on
      the lysing activity of PLA(2) were examined in vitro. Liposomes (lipid model
      membrane) containing phosphatidylcholine (PC) were used as the substrate, on the
      assumption that they are appropriate representatives of SAPL. RESULTS: HA adhered
      to the phospholipid membrane (liposomes), inhibiting their lysis by PLA(2).
      However, in its degraded form, HA not only failed to inhibit PLA(2)-lysing
      activity, but accelerated it. CONCLUSIONS: It is reasonable to assume that HA
      plays an important indirect role in the steady state of the boundary lubrication
      process of joints by protecting SAPL from being lysed by PLA(2). However, as
      excessive loading generates free radicals within the joint (among other effects),
      the HA that is degraded in this way is incapable of protecting SAPL from lysis by
      PLA(2). When the rate of degradation exceeds that of synthesis, there will be
      insufficient replacement of HA and/or SAPL, resulting in denudation of the
      articular surfaces. These are then exposed to increasing friction, and hence
      increased danger of degenerative joint changes.

PMID- 11285384
TI  - Late reactivation of spinal tuberculosis by low-dose methotrexate therapy in a
      patient with rheumatoid arthritis.

PMID- 11285385
TI  - Tumoral enthesopathy in psoriasis.

PMID- 11285386
TI  - Chronic exertional compartment syndrome of the forearms secondary to weight
      training.

PMID- 11285387
TI  - Henoch-Schonlein purpura following meningitis C vaccination.

PMID- 11285388
TI  - Poncet's disease in a patient with AIDS.

PMID- 11285390
TI  - Fibromyalgia syndrome.

PMID- 11285389
TI  - Polymyalgia rheumatica and IUCDs.

PMID- 11285391
TI  - Fibromyalgia-monotheories, monotherapies and reductionism.

PMID- 11285392
TI  - Pyrexia and normal C-reactive protein (CRP) in patients with systemic lupus
      erythematosus: always consider the possibility of infection in febrile patients
      with systemic lupus erythematosus regardless of CRP levels.

PMID- 11285393
TI  - Secondary spontaneous pneumothorax in a patient with pulmonary rheumatoid nodules
      during treatment with methotrexate.

PMID- 11285394
TI  - First presentation of intestinal bypass syndrome 18 yr after initial surgery.

PMID- 11285395
TI  - Thyroid disease in systemic lupus erythematosus and rheumatoid arthritis.

PMID- 11285396
TI  - Jaccoud's arthropathy of the hands as a complication of pyrophosphate
      arthropathy.

PMID- 11285397
TI  - Isolated digital infarction associated with anticentromere antibody.

PMID- 11285398
TI  - EMO syndrome as a late explanation for pretibial swelling.

PMID- 11285399
TI  - Bone mineral density in Marfan syndrome.

PMID- 11285401
TI  - Syringocystadenoma papilliferum: a study of potential tumor suppressor genes.
AB  - Syringocystadenoma papilliferum (SP) is a benign tumor most commonly located on
      the scalp or face, which frequently arises from a nevus sebaceus (NS). Transition
      of SP to basal cell carcinoma (BCC) and, albeit rarely, to metastatic
      adenocarcinoma may occur. Allelic deletions of the human homologue of the
      drosophila patched gene (PTCH) occur in both NS and BCC. To search for genetic
      changes in SP, a microdissection-based genetic analysis using polymorphic markers
      at 9q22 (PTCH; D9S15, D9S303, D9S287, D9S252) as well as markers at 9p21 flanking
      the tumor suppressor gene p16 (IFNA, D9S171) was performed. Glandular epithelium
      consisting of two rows of cells as well as adjacent normal tissue or inflammatory
      infiltrates in the stroma, when present, was dissected and subjected to single
      step DNA extraction and loss of heterozygosity (LOH) analysis. Two of 10
      informative SP cases showed LOH at 9q22 (PTCH). Three of 7 informative SP cases
      showed allelic deletions at 9p21 (p16). Allelic loss at 9q22 is consistent with
      the clinical observation of transition of SP to BCC. The finding of frequent
      allelic loss at 9p21 is unlikely to be related to the rare transition of SP to
      metastatic adenocarcinoma. Our study supports the hypothesis of a gatekeeper role
      of the tumor suppressor gene p16 in a variety of benign and malignant tumors,
      including SP.

PMID- 11285402
TI  - Proliferation and differentiation of the keratinocytes in hyperplastic epidermis
      overlying dermatofibroma: immunohistochemical characterization.
AB  - Epidermal changes overlying dermatofibromas (DFs) have been described as ranging
      from psoriasiform simple hyperplasia to basaloid hyperplasia sometimes
      morphologically indistinguishable from superficial basal cell carcinoma (BCC). To
      characterize epidermal hyperplasia overlying DFs and to determine its association
      with the disease process, we examined 30 cases of DF showing hyperplastic
      epidermis. We used nine immunohistochemical markers associated with keratinocyte
      proliferation or differentiation. In DFs, the dermal metallothionein (MT)
      expression and immunophenotypic changes with regard to epidermal differentiation
      varied depending on the stage of lesional evolution of the DFs. Immunostaining
      for epidermal growth factor receptor (EGFR), MT, and keratin 6 (K6) increased in
      simple hyperplastic epidermis (SHE) overlying DFs (n = 11), whereas it gradually
      diminished in basaloid hyperplastic epidermis (BHE) overlying DFs (n = 19). In
      SHE, there was a significant increase in K14 expression. Among 19 BHE cases, 12
      showed premature expression of involucrin and delayed appearance of K1 along with
      aberrant expression of K14. Conversely, the remaining 7 BHE cases showed a
      pattern of involucrin and K1 similar to that of normal skin coinciding with
      decreased or absent dermal MT expression. Loricrin and filaggrin expression in
      all DFs was the same as that of normal skin. Based on the sparse positivity of Ki
      67 in the hyperplastic epidermis overlying DFs, we found that the biologic
      ability of BHE and SHE was not apparent in the hyperproliferative state observed
      in psoriasis and BCC. These results suggest that the dermal fibrohistiocytic
      process may trigger the induction of SHE overlying DFs by an unknown mechanism
      and then mediate both the abnormal keratinocyte differentiation and the
      transformation of SHE to BHE through the evolution of the dermal lesions.

PMID- 11285403
TI  - Molluscum contagiosum: histologic patterns and associated lesions. A study of 578
      cases.
AB  - Molluscum contagiosum (MC) is rarely associated with other skin diseases,
      especially cutaneous neoplasms. Such associations are exceptional and of unknown
      frequency. The aim of this study was to record the histologic variants and
      frequency of associated lesions in a large series of consecutive MC cases. We
      reviewed 578 MC cases from the Laboratory of Dermatopathology of the University
      Hospitals of Strasbourg, France (1959-1999). The locations of MC were as follows:
      head and neck (34.7%), trunk (27.1%), lower limbs (20.7%), upper limbs (8.7%),
      and genitalia (3.8%). Molluscum contagiosum occurred more often in female
      patients (56.7%). The age range of patients included in this study was 0 to 19
      years (34.9%), 20 to 39 years (31.1%), 40 to 59 years (22.8%), and over 60 years
      (6.5%). Histologic variants of MC were noted in 46 cases (31 pseudocystic, 8
      giant, and 7 pedunculated). An underlying abscess was present in 65 cases. Of the
      578 cases, 22 were associated with other lesions (3.8%). There were 9 cases of
      epidermal cysts, 4 of nevocellular nevi, 3 of metaplastic ossifications, 2 of
      true epidermal nevi, 2 of sebaceous hyperplasias, 2 of soft fibromas, and 1 of
      Kaposi sarcoma. Except in immunocompromised patients, such associations are
      likely to be coincidental. The clinical diagnosis was correct in 42.3% of the
      cases. Clinical accuracy varied according to the age, localization, and
      histologic pattern of MC. Pseudocystic MC, giant MC, and MC associated with other
      lesions were responsible for frequent clinical misdiagnosis.

PMID- 11285404
TI  - "Juvenile" xanthogranuloma: an immunophenotypic study with a reappraisal of
      histogenesis.
AB  - The non-Langerhans histiocytoses, a nosologic category to which juvenile
      xanthogranuoma (JXG) belongs, represent a heterogenous collection of disorders
      related to the monocyte/macrophage lineage. The dermal dendrocyte was previously
      proposed as the cell of origin for JXG on the basis of Factor XIIIa reactivity, a
      suggestion that does not fully explain the occasional xanthogranulomatous
      proliferations localizing exclusively to extracutaneous sites. This study applies
      a panel of recently developed immunohistochemical markers to JXGs and relates the
      phenotype of this process to new concepts of monocyte/dendritic cell ontogeny.
      Twenty-seven JXG, ten dermatofibromas (DF), and ten age-matched normal skin
      specimens were stained using standard immunohistochemistry methods, and all JXGs
      were fascin+ and CD68+, although 26 of 27 were reactive for HLA-DR, 25 of 27 for
      Factor XIIIa, 25 of 27 for LCA, 21of 27 for CD4, and 8 of 27 for polyclonal s100.
      Six of those eight polyclonal S100+ cases were also reactive for monoclonal S100.
      None of those cases was reactive for CD1a, CD3, CD21, CD34, or CD35. Eight of ten
      dermatofibromas were FXIIIa+; all were negative for HLA-DR, LCA, CD4, and
      polyclonal s100. In controls, fascin+ dendritic cells were present but did not
      stain for Factor XIIIa, S100, or CD4. Based on the morphologic and phenotypic
      overlap of the lesional cells in JXGs and plasmacytoid monocytes, it would appear
      that the plasmacytoid monocyte might be considered the putative normal
      counterpart of the major cellular population of JXGs, a proposal that helps
      explain the extra-cutaneous, visceral, and soft tissue location that have been
      reported for occasional cases of JXG. We would also conclude that neither Factor
      XIIIa-nor S100+ results should preclude the diagnosis of JXG, and find that
      reactivity for CD4 and LCA may be used to distinguish JXG from DF when the latter
      is heavily lipidized or the former is not.

PMID- 11285405
TI  - Fibrous spindle cell lipoma: report of a new variant.
AB  - Spindle cell lipoma is a benign tumor characterized by mature fatty tissue
      alternating with short fascicles of small spindle cells in a stroma that varies
      from fibrous to myxoid. The variable proportion of these elements among different
      examples of the neoplasm confers to spindle cell lipoma a variable microscopic
      appearance that can make the diagnosis difficult. Furthermore, in some instances,
      spindle cell lipoma may resemble liposarcoma, hemangiopericytoma, neurilemmoma,
      and other neoplasms representing a histopathologic pitfall. We report on two
      cases of spindle cell lipoma with abundant fibrous stroma reminiscence of fibroma
      and fibrolipoma. The name fibrous spindle lipoma is proposed for this tumor.

PMID- 11285406
TI  - Benign cutaneous Degos' disease: a case report with emphasis on histopathology as
      papules chronologically evolve.
AB  - The following case report details a 53-year-old man with a 6-year history of the
      benign cutaneous or skin-limited form of Degos' disease. Clinically, the patient
      demonstrated a diffuse eruption of papules on the upper trunk and arms. Many
      papules demonstrated the classic porcelain-white centers characteristic of Degos'
      disease, but others exhibited different clinical morphologies that corresponded
      to the evolutionary stages of papules originally described by Degos. Over the
      course of several clinic visits, the patient underwent a total of 5 punch
      biopsies, the histologies of which were correlated with their clinical
      morphologies. Early papules were skin-colored and demonstrated a superficial and
      deep perivascular, periadnexal, and perineural chronic inflammatory cell
      infiltrate associated with interstitial mucin deposition. The overlying epidermis
      showed a mild vacuolar interface reaction and the histologic appearances at this
      early stage resembled tumid lupus erythematosus. Fully developed papules were
      raised with umbilicated porcelain-white centers and a surrounding erythematous
      rim. Histologically these exhibited a prominent interface reaction with
      squamatization of the dermo-epidermal junction, melanin incontinence, epidermal
      atrophy, and a developing zone of papillary dermal sclerosis that resembled the
      early stages of lichen sclerosus et atrophicus in miniature. These interface
      reactions were invariably confined to the central portion of the punch biopsy
      specimen, corresponding to the central porcelain-white area seen clinically.
      Additional features of fully developed papules included a prominent lymphocytic
      vasculitis affecting venules, a mild periadnexal infiltrate of neutrophils and/or
      eosinophils, and interstitial mucin deposition. In late-stage papules, the
      porcelain-white areas were better developed and the lesion flattened.
      Histologically, the degree of inflammation was generally sparse and the overall
      picture mirrored the classic histologic description of Degos' disease with a
      central roughly wedge-shaped zone of sclerosis surmounted by an atrophic
      epidermis and hyperkeratotic compact stratum corneum. These late-stage papules
      closely resembled a miniaturized version of fully developed lichen sclerosus et
      atrophicus confined to the center of the punch biopsy specimen.

PMID- 11285408
TI  - Annular verrucous psoriasis with exaggerated papillomatosis.
AB  - Psoriasis is a disease of substantial clinical and microscopic diversity. We
      report a case of annular verrucous psoriasis associated with abnormal
      papillomatosis, resulting in finger-like projections. We believe that this
      finding may represent another odd histopathologic feature in psoriasis with
      verrucous and rupial clinical morphology.

PMID- 11285407
TI  - Anetoderma arising in cutaneous B-cell lymphoproliferative disease.
AB  - Anetoderma is circumscribed atrophy of the skin due to a localized deficiency in
      elastic tissue. It can follow inflammatory skin diseases of several types, and
      occasionally is present in the skin around neoplasms. There are a few reports of
      anetoderma in the lesional skin of cutaneous lymphoma. We report on two patients
      who presented with multiple lesions of anetoderma and who later proved to have
      low-grade cutaneous B-cell lymphomas. One patient (Patient 1) is a 39-year-old
      man and the other patient is a 26-year-old woman who is a renal transplant
      recipient (Patient 2). Some biopsy specimens from the anetodermic skin of Patient
      1 appeared to show an urticarial reaction, although plasma cells were present. A
      large nodule showed lymphoid follicles surrounded by plasmacytoid lymphocytes,
      with loss of elastic tissue in the adjacent dermis. The plasmacytoid cells
      stained overwhelmingly for lambda light chain, and staining of the urticarial
      lesions from this patient also showed a marked majority of lambda positive cells.
      Immunoglobulin heavy chain gene (IgH) rearrangements showed a dominant clonal
      pattern in the nodular lesion. We classified the disease in Patient 1 as marginal
      zone lymphoma and the disease in Patient 2 as a post-transplant
      lymphoproliferative disorder. Because of the intimate association of anetoderma
      and cutaneous B-cell lymphoproliferative disorders in these two patients, it
      seems possible that anetoderma could result from either a local effect of the
      neoplastic cells or associated inflammatory cells, especially neutrophils as in
      Case 1. The infiltrates of Case 1 had many interstitial neutrophils and only a
      few clonal plasmacytoid lymphocytes, indicating that this presentation of B-cell
      lymphoma can be a diagnostic pitfall. Given these two cases and similar ones in
      the literature, biopsy of lesional skin in anetoderma should be performed to
      ensure that lymphomatous infiltrates are not present. Even if plasma cells are
      sparse, studies to detect clonality are appropriate. Cutaneous B-cell lymphoma
      can be added to the list of associations of elastolysis and cutaneous lymphoma,
      which includes granulomatous slack skin (T-cell lymphoma) and cutis laxa
      (myeloma).

PMID- 11285409
TI  - Middermal elastolysis in two patients with lupus erythematosus.
AB  - Despite lupus erythematosus (LE) being considered a "connective tissue disease,"
      little has been written about the elastic fiber changes in the skin of affected
      patients. We report our histologic findings in two patients with unusual
      cutaneous lesions. Elastic fiber loss was noted, and scattered giant cells with
      elastic fiber phagocytosis were prominent in one patient. The findings are
      similar to those described for middermal elastolysis. Other authors have reported
      patients with LE and elastic fiber loss resembling anetoderma. We believe that a
      spectrum of elastic fiber changes can occur in patients with LE and may be
      induced by infiltrating lymphocytes and/or circulating antibodies.

PMID- 11285410
TI  - An unusual melanocytic lesion associated with eccrine duct fibroadenomatosis and
      syringoid features.
AB  - The intimate association of nevomelanocytic nevi with eccrine ducts commonly seen
      in congenital nevi was emphasized by Mishima, who described as eccrine-centered
      nevi those lesions characterized by nevomelanocytic cells predominantly
      proliferating around and within the eccrine sweat duct walls. However, there were
      no changes in the overlying epidermis, dermis, or eccrine acrosyringeal or dermal
      duct proliferation in these lesions. We present the case of a 16-year-old boy
      with a 1-year-history of a 0.6-cm diameter single tan papule on the right heel,
      clinically thought to be a Spitz nevus. Histopathologic examination revealed a
      compound nevomelanocytic nevus associated with epidermal hyperplasia, thin
      anastomosing cords of acrosyringeal epithelium extending within the dermis, and
      eccrine ductal proliferation in a syringoma-like pattern associated with a dense
      fibrous stroma. Features that distinguish our case from eccrine-centered nevus
      are that the latter lacks epidermal and eccrine duct hyperplasia and a dense
      fibrous stroma. The location of the lesion on the heel in our case suggests the
      possibility that the pathologic changes observed could result from repetitive
      trauma.

PMID- 11285411
TI  - Clear cell trichoblastoma in association with a nevus sebaceus.
AB  - Nevus sebaceus is a hamartoma that is frequently associated with various
      neoplasms. Among the neoplasms observed in sebaceus nevi, trichoblastomas are the
      most common. The present case, to my knowledge, is the first description of a
      clear cell variant of trichoblastoma.

PMID- 11285412
TI  - Herpesvirus infection of seborrheic keratoses.
AB  - We present three examples of patients with seborrheic keratoses complicated by
      necrotizing herpesvirus infection. Two patients had localized cutaneous herpetic
      infections, and the third patient had a generalized cutaneous herpesvirus
      infection. Two of the lesions were thought to be squamous cell carcinoma. The
      third was clinically identified as inflamed seborrheic keratosis. Herpesvirus
      infection was not clinically suspected in two of the patients. The histologic
      changes were similar in all cases. Epidermal proliferation was accompanied by
      hyperkeratosis and pseudo horn cyst formation. Extensive keratinocyte necrosis
      was present along with balloon degeneration of keratinocytes, herpetic viral
      inclusions, and multinucleated giant cells. Viral lesions of molluscum
      contagiosum and human papillomavirus have been observed in benign skin
      proliferations. Nevertheless, we were unable to find descriptions of herpesvirus
      involvement in seborrheic keratosis in a Medline search. Necrotic seborrheic
      keratoses should be carefully examined for the possibility of herpesvirus
      infection, a condition that may be improved by prompt medical intervention as
      demonstrated in one of our cases.

PMID- 11285413
TI  - Localized Birt-Hogg-Dube syndrome with prominent perivascular fibromas.
AB  - The autosomal dominant Birt-Hogg-Dube syndrome is a cutaneo-intestinal condition
      that manifests on the skin in the form of multiple, skin-colored small papules
      that, histologically, prove to be mantleomas (fibrofolliculomas and
      trichodiscomas). These cutaneous lesions usually appear in the region of the
      head, neck, and upper part of the trunk. To date, only a single report in the
      literature describes the localized occurrence of this syndrome. We now describe a
      localized form of the Birt-Hogg-Dube syndrome in a man with multiple mantleomas
      that were confined to the left half of the face, and which, in part, were
      arranged in the form of plaques. Another striking finding in this patient was a
      conspicuous vascular component in the lesions, characterized by a pronounced,
      well-demarcated fibrosis in the region of cutaneous blood vessel proliferations.
      Because perivascular fibromas have already been observed in other patients with
      Birt-Hogg-Dube-syndrome, the perivascular fibroma, with fibrofolliculoma and
      trichodiscoma, must be included within this syndrome's spectrum of skin changes.

PMID- 11285414
TI  - Aggressive digital papillary adenocarcinoma: a case report and review of the
      literature.
AB  - We report a case of an aggressive digital papillary adenocarcinoma (ADPA) on the
      right thumb of a 48-year-old white man. Histologic evaluation of the initial
      biopsy demonstrated features consistent with those proposed for aggressive
      digital papillary adenoma; however, re-excision of the remaining lesion revealed
      histologic features consistent with aggressive digital papillary adenocarcinoma.
      These tumors have a high rate of local recurrence and can metastasize,
      occasionally resulting in mortality. Our case demonstrates that even if the
      histologic criteria of aggressive digital papillary adenocarcinoma are met, the
      lesion may still represent an aggressive digital papillary adenocarcinoma
      (ADPAca). In agreement with a recent study by Duke et al., this case supports the
      idea that aggressive digital papillary lesions should be classified as aggressive
      digital papillary adenocarcinoma.

PMID- 11285415
TI  - On the cover. Proliferations of spindled cells.

PMID- 11285416
TI  - Atypical histologic features in melanocytic nevi.

PMID- 11285418
TI  - Histopathology of psoriasis treated with zinc pyrithione.

PMID- 11285420
TI  - Transforaminal interbody fusion versus anterior-posterior interbody fusion of the
      lumbar spine: a financial analysis.
AB  - Lumbar interbody fusion can be performed anteriorly or posteriorly. An anterior
      approach generally requires an access surgeon and often is combined with a
      posterior fusion. A traditional posterior interbody fusion can destabilize the
      spinal motion segment and requires neural retraction. A new surgical technique, a
      transforaminal lumbar interbody fusion (TLIF), was recently described. It
      requires minimal neural retraction, and the disk space is exposed
      posterolaterally with removal of only one facet joint. This study compares the
      cost of an anterior-posterior one-level lumbar fusion with the cost of the same
      procedure performed using the TLIF technique. Table 1 lists the specific
      demographics. A retrospective review of the hospital charges of 80 patients
      undergoing interbody lumbar stabilization was conducted. The two groups consisted
      of 40 patients with an anterior-posterior fusion and 40 patients who were fused
      circumferentially using the TLIF technique. A cost analysis with normalization of
      1998 dollars between the two groups was performed. The TLIF group had an average
      operative time of 213 minutes, compared with 269 minutes for the anterior
      posterior group. In addition, an average additional 38 minutes were required to
      turn the patient from the anterior or posterior position. The average blood loss
      for the anterior-posterior procedure was 969 mL, compared with 489 mL for the
      TLIF group. Twenty-three of the anterior-posterior patients received an average
      of 2.2 units of blood and six of the TLIF patients received an average of 1.3
      units. Use of the surgical intensive care unit was much lower in the TLIF group
      (38 of 40 patients versus 2 of 40 patients). The average length of stay was 6.1
      days for the anterior-posterior group compared with an average of 3.3 days for
      the TLIF group. The average cost of the anterior-posterior patients was $49,085,
      compared with $33,784 for the TLIF group. Cost analysis between the two groups
      show the TLIF patients had an average savings of approximately $15,000 per
      admission. This cost comparison was conducted only for the time of the operative
      procedure. No attempt was made to analyze rates of fusion between the two groups
      or ultimate clinic outcome. There were no major complications in either group,
      and no patient returned to surgery for a lumbar spinal problem at the authors'
      hospital within 1 year of the index procedure.

PMID- 11285419
TI  - Minimum 10-year follow-up study of anterior lumbar interbody fusion for isthmic
      spondylolisthesis.
AB  - The aims of the current study were to evaluate the long-term clinical and
      radiologic results of anterior lumbar interbody fusion (ALIF) for isthmic
      spondylolisthesis. Between 1981 and 1988, a total of 35 patients underwent ALIF
      for isthmic spondylolisthesis. Of these, 23 patients were followed clinically and
      radiographically for more than 10 years (average, 13.3 years). The Japanese
      Orthopaedic Association low-back pain score was used to evaluate the outcome of
      subjective symptoms and clinical signs. The preoperative and postoperative
      percentage of slip, preoperative and postoperative intervertebral disk height,
      interbody graft union, and pars defect union were evaluated by serial
      radiographs. The adjacent disk degeneration was also evaluated by radiographs and
      magnetic resonance imaging. Although the low-back pain score worsened after 5
      years, ALIF provides satisfactory overall long-term clinical results. The
      preoperative percentage of slip and the disk height were corrected after surgery,
      but at the time of interbody graft union, slip and disk height recurred as a
      result of grafted bone collapse. The rate of union in the grafted area was 83%.
      In the nonunion cases, the scores gradually deteriorated with time, but the
      overall results were not different from those of union cases. Radiographs showed
      adjacent disk degeneration in 52% of cases in the upper adjacent level and in 70%
      of cases in the lower adjacent level, but these changes were not correlated with
      clinical outcomes.

PMID- 11285421
TI  - Containment and stabilization of bone graft in anterior lumbar interbody fusion:
      the role of the Hartshill Horseshoe cage.
AB  - The Hartshill Horseshoe cage is a titanium implant that is inserted after removal
      of the disc in anterior lumbar interbody fusion. The authors use
      corticocancellous iliac crest graft, which is contained within the confines of
      the implant. The cage and the motion segment are stabilized by inserting screws
      into the adjacent vertebral bodies through holes in the implant. Between 1995 and
      1997, 27 patients had this implant inserted. Minimum follow-up was 2.1 years
      (mean: 2.9 years). Patients were assessed using the Oswestry disability index, a
      core set of six questions, a pain drawing, and psychometrically using the Zung
      Depression Scale and the Modified Somatic Perception Questionnaire. The patients'
      subjective assessment was also obtained. Twenty-one patients (77.8%) improved
      significantly on the Oswestry disability index and 22 patients (81.5%) improved
      by subjective assessment using the "core set" of six questions. There was no
      evidence of pseudarthrosis, loosening, or osteolysis around the implant or the
      screws. The cage prevents graft extrusion, collapse, or sinkage through the
      endplates. The normal lumbar lordosis is restored and, by restoring normal
      intervertebral disc space height, the Horseshoe opens up the neural foraminae.
      This cage stabilizes the motion segments and secures the graft, preventing
      micromotion at the graft vertebral body interface and providing a conducive
      environment for fusion.

PMID- 11285422
TI  - Effectiveness of transfixation and length of instrumentation on titanium and
      stainless steel transpedicular spine implants.
AB  - This study compares the effectiveness of transfixation on the stiffness of two
      pedicle screw-rod constructs of different manufacture, implant design, and alloy,
      applied in one-and two-level instability. Four screws composed of either
      stainless steel or Titanium were assembled in pairs to two polymethylmethacrylate
      blocks to resemble one-and two-level corpectomy models and the construct
      underwent nondestructive torsional, extension, and flexion loading. In every
      loading test, each construct was tested using stainless steel or titanium rods of
      4.9-mm diameter in two different lengths (short, 10 cm; long, 15 cm), not
      augmented or augmented with different transfixation devices or a pair of devices.
      The authors compared the stiffness of stainless steel and titanium constructs
      without cross-link with the stiffness of that reinforced with single or double
      Texas Scottish Rite Hospital (TSRH) cross-link, closed new-type cross-link
      (closed NTC), or open new-type cross-link (open NTC). The results showed that
      augmentation or no augmentation of short rods conferred significantly more
      stiffness than that of long rods of the same material in all three loading modes.
      The closed NTC provided the greatest increase of torsional, extension, and
      flexion stiffness, and single TSRH provided the least amount of stiffness.
      Torsional stiffness of short stainless steel rods augmented or not augmented was
      significantly greater than that of their titanium counterparts. Torsional
      stiffness of long titanium rods was always greater than that of their stainless
      steel counterparts. Extension stiffness of short nonaugmented titanium rods was
      superior to that of long titanium rods, whereas extension stiffness of
      nonaugmented short and long stainless steel rods was similar. Nonaugmented short
      titanium rods showed greater flexion stiffness than that of long titanium rods.
      Long stainless steel rods displayed significantly greater flexion stiffness than
      did their titanium counterparts. This nondestructive study showed that cross
      links increase the torsional stiffness significantly but less so the flexion and
      extension stiffness of both titanium and stainless steel posterior transpedicular
      constructs. This increase was proportional to the cross-sectional diameter of the
      cross-link. Titanium constructs showed more torsional stiffness when used in two
      level instability and steel showed more torsional stiffness in one-level
      instability, particularly when they are reinforced. Stainless steel constructs
      showed greater flexion stiffness when they were used in two-level and titanium
      showed greater flexion stiffness in one-level instability, particularly when they
      were reinforced with stiff cross-links. The effect of transfixation on extension
      forces was obvious when thick cross-links were used.

PMID- 11285423
TI  - Sacroiliac arthrodesis using a posterior midline fascial splitting approach and
      pedicle screw instrumentation: a new technique.
AB  - Many techniques for sacroiliac arthrodesis have been described. No single
      technique is universally accepted as the standard. The current report describes a
      new technique using a midline fascial-splitting approach and pedicle screw
      instrumentation. Four consecutive patients with nontraumatic disorders of the
      sacroiliac joint who have undergone successful arthrodesis by the described
      technique are presented. One patient had a spontaneous sacroiliac disruption
      secondary to rheumatoid arthritis, and was returned to her previous ambulatory
      status after fusion of the disrupted joint. Her fusion remained stable for 9
      years postoperatively. The others had degeneration of the sacroiliac joint that
      was symptomatically improved by arthrodesis. The described method of sacroiliac
      arthrodesis may be an attractive option for surgeons who are familiar with
      pedicle screw instrumentation techniques.

PMID- 11285424
TI  - Biomechanics of long segment fixation: hook patterns and rod strain.
AB  - This is an in vitro study of the mechanical effects of varying hook attachment
      patterns in long segment kyphotic deformity. In such cases, the optimal implant
      bulk, fatigue life, and construct rigidity to reliably achieve fusion are still
      unquantified. Rod strains were measured for multiple laminar hook patterns in a
      synthetic thoracic spine test bed. Stresses were calculated from strain data. The
      model displayed similar flexion bending stiffness to the thoracic spine. None of
      the hook patterns significantly changed overall construct stiffness. Greatest rod
      strains were seen when utilizing away-facing apical hooks. This model was too
      stiff to detect differences in construct stiffness. Nonetheless, rod stress
      analysis showed that for multisegment thoracic constructs, particularly with
      fixed kyphosis, minimizing apical hooks will minimize rod strain. If periapical
      hooks are necessary, orienting the hooks toward the apex will minimize rod
      strain.

PMID- 11285425
TI  - Correction method for determining anteroposterior diameter of the cervical spinal
      canal on lateral radiographs.
AB  - SUMMARY: Measurement of the anteroposterior diameter of the cervical spinal canal
      may prove unreliable because of the rotatory effect of degenerative disease.
      Nevertheless, this measuring error may be corrected by performing dual midpoint
      measurements between the posterior vertebral body and spinolaminar line when less
      than 10 degrees of rotation is present.

PMID- 11285426
TI  - Computer-assisted assessment of spinal sagittal plane radiographs.
AB  - The sagittal shape of the spine, particularly its sagittal balance, currently is
      being extensively investigated. The major purpose of this study is to examine the
      measurement repeatability of SpineView software, which calculates 13 independent
      variables, to shorten and facilitate the measurement of lateral spinal
      radiographs; another purpose is to collect physiological data for nonpathologic
      spines, which can be used as a reference in future research. This article also
      presents two new parameters and discusses their possible role in forthcoming
      investigations. The interobserver repeatability study shows that most of the
      variables are more repeatable (less than +/-1.5 degrees ) when the operator is
      experienced. A less (+/-6.5 degrees ) repeatable measurement is T4-T12 kyphosis,
      which may be because of the poor contrast generally observed on radiographs of
      the upper thoracic vertebrae. The intraobserver repeatability study also
      demonstrates that subjective failures do not influence the results significantly,
      but the quality of the radiographs may have significant effect on long-term
      repeatability. The mean values were generally different between male and female
      subjects, and significant differences between the two sexes were only noticed for
      pelvic thickness and global spinal inclination. Normal range values and
      correlations between some pelvic and spinal parameters were similar to data found
      in the literature. The results of the current study provide evidence that the
      SpineView software is useful for experimental investigation of sagittal spinal
      alignment.

PMID- 11285427
TI  - Diagnosis of lumbosacral nerve root anomalies by magnetic resonance imaging.
AB  - This study evaluates the use of magnetic resonance imaging (MRI) in the diagnosis
      of lumbosacral nerve root anomalies. Prevalence of anomalous nerve roots has been
      based on anatomic dissection or preoperative neuroradiologic investigations.
      Three hundred seventy-six patients with low back pain and/or radicular pain who
      underwent MRI of the lumbar spine were reviewed. Sixty-five cases of nerve root
      anomalies were found (an incidence of 17.3%) of which 1 case of cranial origin, 5
      cases of caudal origin, 2 cases of conjoined nerve root, and 57 cases of furcal
      nerve roots (15.1%) were identified. Furcal nerve roots were most commonly found
      at L3 and L4 levels and were classified, according to their division, into intra
      and extraforaminal. MRI provided accurate information on lumbosacral nerve root
      anomalies.

PMID- 11285428
TI  - Localized oxygen use of healthy and low back pain individuals during controlled
      trunk movements.
AB  - Individuals who have low back pain (LBP) have significantly different motion
      characteristics than healthy individuals. However, the cause of these differences
      is unknown. Oxygen use of the erector spinae muscle was examined while
      simultaneously monitoring motion characteristics to determine whether oxygen use
      differed between healthy and LBP individuals. Thirty volunteers were classified
      as healthy, structural, or muscular-based LBP. A near-infrared spectrometer
      monitored oxygen use and blood volume in the lumbar region. Results showed
      significant differences in oxygen use but not blood volume between healthy and
      LBP subjects with muscular-based disorders. Inability of the muscular group to
      use oxygen in a manner similar to the healthy group indicates different processes
      at the tissue level, indicating that differences in oxygen use may provide
      insight into why motion patterns differ between healthy and LBP groups.

PMID- 11285429
TI  - Percutaneous nucleotomy in elite athletes.
AB  - Percutaneous nucleotomy in elite athletes is considered a minimally invasive
      treatment of lumbar disc herniation. However, long-term effectiveness has not
      been established by careful follow-up studies. This article evaluates the outcome
      of percutaneous nucleotomy in elite athletes who have undergone the procedure.
      Thirty elite athletes with lumbar disc herniation who underwent percutaneous
      nucleotomy and had been followed for at least 2 years were compared with a
      matched group of 42 nonathletes. The outcome in athletes was worse than in
      nonathletes. Early return to vigorous sports activity in less than 3 months
      correlated with increased symptoms. Similarly, more extensive resection of disc
      material was associated with an unexpected rapid worsening of the outcome and the
      lower rate of return to preoperative sports. Patient selection and postoperative
      management of athletes and nonathletes undergoing percutaneous nucleotomy should
      be the same, and the procedure in athletes is probably not worthwhile if they do
      not obey postoperative management such as the timing of return to sports
      activity.

PMID- 11285430
TI  - Surgical therapy for dialysis-related spondyloarthropathy: review of 30 cases.
AB  - Surgical therapy for dialysis-related spondyloarthropathy was investigated
      regarding its spinal manifestation. Between August 1985 and May 1998, 31
      operations were performed on 16 male and 14 female patients; of these, 17 had
      cervical and 13 had lumbar spinal disorders. The average patient age was 59
      years. The average period of hemodialysis was 14.8 years. Twenty-eight of 30
      patients had cystic bone lesions and 24 had carpal tunnel syndrome. Four major
      postoperative complications occurred: death from paralysis and respiratory
      distress, severe kyphosis from the collapse of the grafted bone, deep infection
      from instrumentation, and wire breakage and bone fusion failure. Postoperative
      results with an average follow-up period of 2.7 years were good in 19 cases
      (63%), fair in 8 cases (27%), and poor in 3 cases (10%). As yet, surgical
      intervention for dialysis-related spondyloarthropathy is still regarded as a
      noncurative treatment; furthermore, the anterior approach to the cervical spine
      has a high risk for postoperative complications.

PMID- 11285431
TI  - Traumatic subluxation of the axis after hyperflexion injury of the cervical spine
      in children.
AB  - Six cases of children (four boys and two girls, mean age 11 years) who had
      traumatic subluxation of the axis (C2) were reviewed retrospectively. Initial
      radiographs demonstrated no detectable vertebral fracture in any of the children.
      However, a slight anterior subluxation of C2 was observed in three of the
      patients. Radiographs, taken at 1 month after injury in all but one patient,
      revealed a progression of the subluxation and a local kyphosis in all of the
      patients. Four of the children were treated conservatively with a cervical brace,
      and an improvement of both the kyphosis and the anterior slippage of C2 was
      obtained accompanied by an anteroposterior growth of the C3 vertebral body. The
      kyphosis of two of the patients became severe and, ultimately, these patients
      underwent fusion surgery. At the follow-up, none of the patients presented with
      any significant symptom. For the correct diagnosis of traumatic subluxation of
      C2, sequential radiographs to confirm the progression of subluxation and local
      kyphosis are mandatory. Conservative treatment rather than early surgical
      treatment may be chosen for this injury, because mild and moderate kyphosis can
      be corrected spontaneously by remodeling of the cervical spine.

PMID- 11285432
TI  - Sudden sensorineural hearing loss after spinal surgery under general anesthesia.
AB  - Two patients, ages 72 and 71, who underwent lumbar decompressive surgery for
      spinal stenosis, were evaluated for postoperative sudden sensorineural hearing
      loss (SSHL). After two uncomplicated spinal procedures, both patients developed
      SSHL immediately after surgery. Hearing loss was moderate to profound in these
      two patients. None of the patients had a significant otologic history. Nitrous
      oxide administration, Valsalva maneuvers during general anesthesia, and transient
      drops in cerebrospinal fluid pressure stemming from spinal decompression may, in
      some combination, lead to an implosive force on the inner ear, causing SSHL.
      Further causes of postlumbar surgery SSHL may include microemboli or viral
      infections. SSHL is a rare but possible complication after nonotologic,
      noncardiac bypass surgery; only 26 cases of SSHL after this surgery have been
      reported. We encourage the continued reporting of sudden sensorineural hearing
      loss after spinal surgery.

PMID- 11285433
TI  - A guest editorial: update on diethylstilbestrol.

PMID- 11285435
TI  - Leptin in obstetrics and gynecology: a review.
AB  - Leptin, a recently described type-1 cytokine, is involved in cellular maturation
      and growth and appears to have a relationship to some obstetrical and gynecologic
      diseases. The MEDLINE database was accessed, and leptin-related articles
      published during the past 6 years were reviewed for their relevance to
      gynecologic and obstetrical diseases. The relationships between this cytokine and
      obesity, puberty, polycystic ovary syndrome, endometriosis, assisted fertility,
      and menopause are discussed. The role of leptin in fetal physiology and in normal
      and abnormal fetal growth as well as its role in diabetes, pregnancy, and
      pregnancy-induced hypertension are reviewed.

PMID- 11285436
TI  - Lead exposure in pregnancy: a review of the literature and argument for routine
      prenatal screening.
AB  - Despite a steady decline in average blood lead levels in the U.S. population,
      approximately 0.5% of women of childbearing age may have blood levels exceeding
      10 microg/dl. Strong correlations between maternal and umbilical cord blood lead
      levels demonstrate that lead is transferred from the mother to the fetus. High
      lead levels are known to cause neurobehavioral effects in infants and children,
      and the cumulative effects of low levels of lead exposure in utero and after
      birth can have similar detrimental effects. Modern sources of exposure include
      occupational exposure during automotive or aircraft paint manufacturing, lead
      production or smeltering, exposure to stained glass soder, and environmental
      exposure during home renovation. Prenatal screening for lead exposure may include
      use of a five-item questionnaire similar to the pediatric questionnaire.
      Management of prenatal lead exposure focuses on removal of the lead source.
      Rarely, highly toxic chelation therapy is needed for maternal indications.
      Recognition and removal of lead sources during the prenatal period can prevent
      maternal and neonatal morbidity.

PMID- 11285437
TI  - Current concepts in the diagnosis and surgical repair of anterior vaginal
      prolapse due to paravaginal defects.
AB  - Anterior vaginal prolapse is often caused by defects in the paravaginal fascia.
      The purpose of this article is to review the current concepts in the diagnosis
      and surgical repair of anterior vaginal prolapse due to paravaginal defects.
      Articles related to paravaginal defects were identified through a MEDLINE search
      of English-language medical journals published between June 1909 and August 2000.
      Physical examination is usually used to diagnose paravaginal defects, but this
      method may have low specificity and low positive predictive value. Magnetic
      resonance imaging may be used to examine the pelvic anatomy, but it is expensive
      and may not be readily available to all physicians. Transabdominal ultrasound
      does not appear to be useful for detection of paravaginal defects. Paravaginal
      repair, both transvaginal and transabdominal approaches, appears to offer
      favorable cure rates and low recurrence rates of anterior vaginal prolapse.
      Paravaginal repair does not appear to be as effective as Burch colposuspension
      for treatment of stress urinary incontinence. The efficacy of laparoscopic
      paravaginal repair requires additional investigation. Complications including
      voiding dysfunction, hemorrhage, and urinary tract injury are uncommon. The long
      term efficacy of paravaginal repair requires further investigation.

PMID- 11285438
TI  - [An observational, retrospective two-year cost study in primary open-angle
      glaucoma and ocular hypertension in newly diagnosed patients].
AB  - PURPOSE: To investigate the different treatment strategies in France and the
      direct costs for patients with newly diagnosed primary open-angle glaucoma or
      ocular hypertension who have started treatment with beta-blockers, and to
      estimate the total direct cost for two years of treat. MATERIAL: and methods: We
      analyzed 225 medical charts retrospective in eleven academically and office-based
      centers in France over the first two years after diagnosis. Standard costs for
      each resource in current medical practice were determined from the French Social
      Security perspective. RESULTS: The vast majority of patients (90%) had a
      diagnosis of primary, open-angle glaucoma or ocular hypertension in both eyes. In
      60% of the patients we found a moderate or severe defect in their visual field or
      optic nerve. Intraocular pressure before treatment was 23.9+4.7mmHg and
      17.5+4.2mmHg after two years of treatment. Over the first two years, 25% of
      visits led to a change in therapy (medical or surgical), involving 64% of the
      patients. Two-thirds of the changes occurred during the first year of treatment
      and in around 80% of cases for low intraocular pressure at check-up. Laser
      surgery or surgical intervention was performed in 25% of the patients. Total
      direct costs for two years were 5698F.F. The intraocular pressure before
      treatment was positively correlated (p<0.01) with treatment costs, while the
      initial intraocular pressure-lowering effects of treatment were negatively
      correlated with two-year costs. CONCLUSION: After two years of treatment, the
      mean intraocular pressure decreased from 24 to 17.5mmHg. The higher the basal
      intraocular pressures is, the more intensive the treatment and the higher the
      costs. The more efficient the treatment to decrease baseline intraocular pressure
      is, the earlier the costs will be reduced.

PMID- 11285439
TI  - [Clinical course and prognosis of diplopias after orbital bony wall decompression
      for thyroid related orbitopathy].
AB  - INTRODUCTION: The aim of this study was to assess how oculomotor complications
      progress after orbital bony decompression for dysthyroid orbitopathy and to
      assess the residual risk of consecutive diplopia. MATERIAL AND METHODS: The
      medial orbital wall and floor were decompressed by a transpalpebral approach in
      77 patients (117 orbits). Indications for decompression were optic neuropathy in
      22 patients, exposure of the cornea in 1 patient, and cosmetic rehabilitation in
      54 patients. Occurrence of oculomotor disorder after surgery was noted and the
      clinical course after a one-year follow-up was studied. RESULTS: Diplopia was
      observed in 34 patients (44%): 18 of these patients were treated by external
      orbital radiotherapy before surgery. Diplopia decreased spontaneously over a
      period ranging from 15 days to 2 months or was treated by adequate prism in 22
      cases. A higher degree of diplopia (12 to 30 diopters) was noted in 12 cases,
      requiring surgical care that was successful in all cases. This progress was
      especially observed in patients with optic neuropathy or in patients who had been
      previously treated with external orbital radiotherapy. CONCLUSION: Prognosis of
      diplopia after bony wall decompression for thyroid-related orbitopathy can be
      favorable with spontaneous reduction, prism, or surgical treatment. Precise
      information should be given to the patients before surgery.

PMID- 11285440
TI  - [Holmium: YAG and neodymium: YAG laser assisted trans-canalicular
      dacryocystorhinostomy. Results of 317 first procedures].
AB  - PURPOSE: To assess the results of the first procedures of trans-canalicular
      dacryocystorhinostomy according to two different lasers: Neodymium: YAG (Nd: YAG)
      laser or Holmium: YAG (Ho: YAG) laser. To study the efficiency of two anti
      metabolite drugs: mitomycin-C (MMC) and 5 fluoro-uracile (5 FU). To analyse the
      rate of efficiency of the Ho: YAG laser in the canalicular obstructions. METHODS:
      Three hundred and seventeen patients were operated: 226 with the Nd: YAG laser,
      77 with the Ho: YAG laser and 14 with both lasers; 68 were treated with an
      application of MMC and 40 patients with an application of 5-FU. Sixty-three
      patients suffered from a canalicular obstruction. RESULTS: The results are based
      on 289 procedures 6 months after the operation. The global rate of success was
      63.32% after one intervention and 70.24% after one or two revisions. There is no
      statistically significant difference between Nd: YAG or Ho: YAG lasers. The use
      of antimetabolites did not improve the success rate. In 65% of the cases the
      canalicular patency is reached. CONCLUSION: Laser-assisted transcanalicular
      dacryocystorhinostomy is a very useful method because it does not cause cutaneous
      scarring and for it has a low rate of morbidity given that it causes very little
      surgical traumatism. Consequently, it can be used under topical anaesthesia and
      for patients at risk or suffering from coagulation problems. It can be undertaken
      in the cases of extremely narrow nasal fossae when an endonasal
      dacryocystorhinostomy is impossible. This procedure is less successful than
      external or endonasal dacryocystorhinostomy. The success rate is not modified by
      the use of antimetabolites or by the type of laser.

PMID- 11285442
TI  - [Capsulorhexis staining by trypan bleu in mature cataract surgery].
AB  - BACKGROUND: Capsulorrhexis may be hazardous in the absence of the red fundus
      reflex. Anterior capsule trypan blue staining enabled to perform the
      capsulorrhexis and safe phacoemulsification. MATERIAL AND METHODS: Twenty
      patients with mature cataract were enrolled in the study and opereted on after
      injection of trypan blue in the anterior chamber. RESULTS: Circular
      capsulorrhexis was performed in all cases followed by phacoemulsification and in
      the-bag IOL implantation. In two cases hard nuclei required a manual
      extracapsular technique. No operative complications, and no residual of
      coloration was noted the day after the operation. With a follow-up of 2 to 12
      months, no complications appeared (cornea, capsulorrhexis, IOP). CONCLUSION: In
      mature cataracts, with no red fundus reflex, capsulorrhexis can be done by
      anterior capsule staining.

PMID- 11285441
TI  - [Revision of failed dacryocystorhinostomies using the transcanalicular approach.
      Results of 118 procedures].
AB  - PURPOSE: To assess the efficacy of transcanalicular dacryocystorhinostomy for the
      revision of other procedures. The results are analyzed following the use of two
      different types of laser: the Neodymium: YAG (Nd: YAG) laser and the Holmium: YAG
      (Ho: YAG) laser. To study the efficacy of using two antimetabolite drugs in this
      context: mytomycin-C (MMC) and 5-fluoro-uracile (5-FU). METHODS: One hundred and
      fourteen patients were operated on. Of these, 88 had already undergone one
      procedure, 25 two procedures, and 5 three procedures. The Nd: YAG laser was used
      in 78 procedures, the Ho: YAG in 30 procedures, and both lasers in 10 procedures.
      Twenty patients were treated with an application of MMC and 25 patients with an
      application of 5-FU. RESULTS: The results are based on 106 procedures. The total
      success rate was 49.06% after one revision and 58.49% after two or three
      revisions. There is no statistically significant difference between the Nd: YAG
      and Ho: YAG lasers. The use of antimetabolites did not improve the success rate.
      CONCLUSION: Transcanalicular dacryocystorhinostomy is a very useful method
      because it does not cause cutaneous scarring and it has a low rate of morbidity
      given that it causes very little surgical traumatism. The revision of other
      dacryocystorhinostomy methods using the transcanalicular approach is
      theoretically a positive indication because it does not dissect scarring tissues
      and because the osteotomy has already been performed. However, the success rate
      is lower than for the external and endonasal approaches. The success rate is not
      modified by the use of antimetabolites or by the type of laser.

PMID- 11285443
TI  - [Tolerance of orbital implants. Retrospective study on 14 years].
AB  - The authors report the results of enucleations performed from 1985 to 1998 and
      the different orbital implants used. MATERIAL AND METHODS: All patients
      undergoing enucleation from 1985 to 1998 were studied. RESULTS: 68 men and 32
      women had an enucleation. The main indication was tumoral diseases, principally
      choroidal melanomas and ciliary melanomas (respectively, 26 and 8). More rarely
      the indication was orbital metastasis or eyelid carcinoma. The follow indications
      were traumatisms and neovascular glaucomas. The orbital implants used were mainly
      Allen implants, silicone implants and hydroxyapatite implants. The main
      complication was the expulsion of the implant, which occurred in about 20% of the
      cases, for the most part in the group of silicone and tunnel implants patient.
      These expulsions were found less with hydroyxapatite implants. For the
      hydroxyapatite implants we also noticed the some conjunctival erosion. The
      expulsion of the implant occurred most often before 2 years. CONCLUSION: The
      authors report on the survey of orbital implants used for 14 years. They noticed
      the high frequency of expulsions when they used tunnel or silicone implants and
      better results with hydroxyapatite implant.

PMID- 11285444
TI  - [Treatment of post-traumatic cyclodialysis using by direct cyclopexy].
AB  - INTRODUCTION: We report 2 cases of posttraumatic cyclodialysis treated by direct
      cyclopexy. We decided to operate because of the presence of a macular and disc
      oedema after an ocular chronic hypotony. PATIENTS: The case was a blunt ocular
      trauma and the other case a perforating injury. For the latter, a cycloplegic
      treatment was ineffective. The ocular hypotony persisted 2 months in the first
      case and 2 and a half years in the second. In both cases, the hypotony was major
      (0mmHg) and the cyclodialysis cleft was extended to 90 degrees (in the superior
      temporal quadrant and the inferior nasal quadrant). A direct cyclopexy was
      performed with cilioscleral sutures with 10-0 monofilament. RESULTS: One patient
      presented a moderate and temporary postoperative hypertony. The maximal follow-up
      was 9 months: ocular tonus was normalized (10 and 11mmHg), the fundus aspect was
      improved, and visual acuity was either the same (hand movement perception) or
      increased from 0.1, 14 to 1.0, 2 on the Parinaud scale. DISCUSSION: The direct
      cyclopexy was effective in both cases. It precisely defined the cyclodialysis
      limits, it allowed the suprachoroidal fluid to drain and restored the anatomic
      features. Moreover, it allowed treating larger cyclodialysis for which a simple
      laser treatment would be incomplete. On the other hand, it was invasive
      intraocular surgery which presented risks of hemorrhage, infection and retinal
      detachment. CONCLUSION: The direct cyclopexy is an advisable method in the
      treatment of cyclodialysis. It normalized an ocular tonus and improved of
      hypotonus retinopathy. However, vision remained sometimes limited because of the
      posttraumatic sequels are or ocular hypotony that was too lengthy.

PMID- 11285445
TI  - [Orbital metastasis in malignant melanoma].
AB  - We report the case of a 60-year-old man presenting bilateral progressive
      proptosis with diplopia, weight loss, tachycardia, nervosity, and stomach pain.
      These signs seemed at first to favor a diagnosis of Graves'ophthalmopathy.
      Thyroid tests were negative and the initial orbital CT scan was considered
      normal. A new radiological investigation 4 months later in our hospital revealed
      typical hypertrophy of the extraocular muscles compatible with orbital
      metastasis. The systemic investigations demonstrated a pulmonary tumor, multiple
      hepatic lesions, and several pigmented nodules of gastric mucosa. The pathology
      of pulmonary and gastric specimens confirmed the diagnosis of malignant melanoma.
      The primary lesion remains unknown. The authors discuss the differential
      diagnoses of orbital metastasis and the radiological characteristics of orbital
      metastasis in malignant melanoma.

PMID- 11285446
TI  - [Retinal lesion due to an obstetrical traumatism: a case report].
AB  - The authors report a case of unilateral, stable, localized, and well
      circumscribed choriocapillaris atrophy associated with retinal pigment epithelium
      dispersion and atrophy. The anterior segment was normal. Facial examination
      revealed a homolateral malar hypoplasia. The other eye was normal. The
      electrophysiologic study did not confirm pigmentary degeneration of the retina.
      The patient's history included a difficult delivery using obstetrical forceps.
      The authors review the main ocular lesions secondary to birth trauma. In this
      case, they favored a traumatic chorioretinal lesion secondary to an obstetrical
      traumatism. In this context, progressive facial hemiatrophy is the main
      differential diagnosis.

PMID- 11285447
TI  - [Traumatic superior orbital fissure syndrome: report of 4 cases and review of
      literature].
AB  - PURPOSE: The authors retrospectively analyzed four cases of posttraumatic
      superior orbital fissure syndrome and reviewed the literature. METHOD: Four
      patients (three male and one female) were followed for this complication in the
      department from october 1995 to december 1996. RESULTS: The mean age was 31
      years, the median follow-up was 8 month. Computed tomography showed involvement
      of the superior orbital fissure but no in three patients, in the fourth. The
      treatment consisted of osteosynthesis of craniofacial fracture in three patients
      and corticosteroid therapy in the last one. All patients presented partial
      recuperation of external ophthalmoplegia and ptosis. Twelve months after the
      traumatism, one patient underwent surgery for persistant ptosis and diplopia.
      CONCLUSION: The superior orbital fissure syndrome is an exceptional complication
      of orbital traumas. Partial recuperation of the neuro-ophthalmologic function
      usually occurs within a period of several months.

PMID- 11285448
TI  - [Urrets-Zavalia syndrome].
AB  - We report four cases of Urrets-Zavalia Syndrome (fixed dilated pupil with iris
      atrophy) observed after penetrating keratoplasty. The precise etiology of the
      syndrome is uncertain and different mechanisms are reviewed. Care should be taken
      to avoid the use of mydriatic eye drops after penetrating keratoplasty.

PMID- 11285449
TI  - [The materials for intraocular lenses. Part III: acrylic foldable intraocular
      lenses].

PMID- 11285450
TI  - [Iontophoresis: past and future].

PMID- 11285451
TI  - [Conjunctival in situ carcinoma in a patient with Waldenstrom's disease].
AB  - A 73-year-old male patient was treated for conjunctival in situ carcinoma
      invading the cornea of his right eye. The patient had been previously operated on
      for two corneoconjunctival lesions on the same eye (one was a pterygium, the
      other was simple epithelial hyperplasia) and was regularly followed for a
      systemic lymphoplasmocytic lymphoma (Waldenstrom's disease). After a
      corneoconjunctival excision of the tumor, the histological analysis was performed
      and established the diagnosis of in situ carcinoma. The tumor recurred a few
      months later and radiation therapy was then given. No recurrence was observed
      after this latter treatment.

PMID- 11285452
TI  - [Deep sclerectomy with cribriform trabecular ablation: a stupendous bet!].

PMID- 11285453
TI  - Protein folding: a perspective for biology, medicine and biotechnology.
AB  - At the present time, protein folding is an extremely active field of research
      including aspects of biology, chemistry, biochemistry, computer science and
      physics. The fundamental principles have practical applications in the
      exploitation of the advances in genome research, in the understanding of
      different pathologies and in the design of novel proteins with special functions.
      Although the detailed mechanisms of folding are not completely known, significant
      advances have been made in the understanding of this complex process through both
      experimental and theoretical approaches. In this review, the evolution of
      concepts from Anfinsen's postulate to the "new view" emphasizing the concept of
      the energy landscape of folding is presented. The main rules of protein folding
      have been established from in vitro experiments. It has been long accepted that
      the in vitro refolding process is a good model for understanding the mechanisms
      by which a nascent polypeptide chain reaches its native conformation in the
      cellular environment. Indeed, many denatured proteins, even those whose disulfide
      bridges have been disrupted, are able to refold spontaneously. Although this
      assumption was challenged by the discovery of molecular chaperones, from the
      amount of both structural and functional information now available, it has been
      clearly established that the main rules of protein folding deduced from in vitro
      experiments are also valid in the cellular environment. This modern view of
      protein folding permits a better understanding of the aggregation processes that
      play a role in several pathologies, including those induced by prions and
      Alzheimer's disease. Drug design and de novo protein design with the aim of
      creating proteins with novel functions by application of protein folding rules
      are making significant progress and offer perspectives for practical applications
      in the development of pharmaceuticals and medical diagnostics.

PMID- 11285454
TI  - Is pancreas development abnormal in the non-obese diabetic mouse, a spontaneous
      model of type I diabetes?
AB  - Despite extensive genetic and immunological research, the complex etiology and
      pathogenesis of type I diabetes remains unresolved. During the last few years,
      our attention has been focused on factors such as abnormalities of islet function
      and/or microenvironment, that could interact with immune partners in the
      spontaneous model of the disease, the non-obese diabetic (NOD) mouse.
      Intriguingly, the first anomalies that we noted in NOD mice, compared to control
      strains, are already present at birth and consist of 1) higher numbers of
      paradoxically hyperactive beta cells, assessed by in situ preproinsulin II
      expression; 2) high percentages of immature islets, representing islet neogenesis
      related to neonatal beta-cell hyperactivity and suggestive of in utero beta-cell
      stimulation; 3) elevated levels of some types of antigen-presenting cells and
      FasL+ cells, and 4) abnormalities of extracellular matrix (ECM) protein
      expression. However, the colocalization in all control mouse strains studied of
      fibroblast-like cells (anti-TR-7 labeling), some ECM proteins (particularly,
      fibronectin and collagen I), antigen-presenting cells and a few FasL+ cells at
      the periphery of islets undergoing neogenesis suggests that remodeling phenomena
      that normally take place during postnatal pancreas development could be disturbed
      in NOD mice. These data show that from birth onwards there is an intricate
      relationship between endocrine and immune events in the NOD mouse. They also
      suggest that tissue-specific autoimmune reactions could arise from developmental
      phenomena taking place during fetal life in which ECM-immune cell interaction(s)
      may play a key role.

PMID- 11285455
TI  - Involvement of calcium in pain and antinociception.
AB  - Calcium ions are widely recognized to play a fundamental role in the regulation
      of several biological processes. Transient changes in cytoplasmic calcium ion
      concentration represent a key step for neurotransmitter release and the
      modulation of cell membrane excitability. Evidence has accumulated for the
      involvement of calcium ions also in nociception and antinociception, including
      the analgesic effects produced by opioids. The combination of opioids with drugs
      able to interfere with calcium ion functions in neurons has been pointed out as a
      useful alternative for safer clinical pain management. Alternatively, drugs that
      reduce the flux of calcium ions into neurons have been indicated as analgesic
      alternatives to opioids. This article reviews the manners by which calcium ions
      penetrate cell membranes and the changes in these mechanisms caused by opioids
      and calcium antagonists regarding nociceptive and antinociceptive events.

PMID- 11285456
TI  - Further biochemical characterization of Mycobacterium leprae laminin-binding
      proteins.
AB  - It has been demonstrated that the alpha2 chain of laminin-2 present on the
      surface of Schwann cells is involved in the process of attachment of
      Mycobacterium leprae to these cells. Searching for M. leprae laminin-binding
      molecules, in a previous study we isolated and characterized the cationic
      proteins histone-like protein (Hlp) and ribosomal proteins S4 and S5 as potential
      adhesins involved in M. leprae-Schwann cell interaction. Hlp was shown to bind
      alpha2-laminins and to greatly enhance the attachment of mycobacteria to ST88-14
      Schwann cells. In the present study, we investigated the laminin-binding capacity
      of the ribosomal proteins S4 and S5. The genes coding for these proteins were PCR
      amplified and their recombinant products were shown to bind alpha2-laminins in
      overlay assays. However, when tested in ELISA-based assays and in adhesion assays
      with ST88-14 cells, in contrast to Hlp, S4 and S5 failed to bind laminin and act
      as adhesins. The laminin-binding property and adhesin capacity of two basic host
      derived proteins were also tested, and only histones, but not cytochrome c, were
      able to increase bacterial attachment to ST88-14 cells. Our data suggest that the
      alanine/lysine-rich sequences shared by Hlp and eukaryotic H1 histones might be
      involved in the binding of these cationic proteins to laminin.

PMID- 11285457
TI  - Genotyping of group A rotavirus samples from Brazilian children by probe
      hybridization.
AB  - The G genotyping of 74 group A rotavirus samples was done by RNA-DNA
      hybridization (dot-blot) using oligonucleotide probes for the VP7 gene region of
      the human rotavirus serotypes/genotypes 1, 2, 3 and 4. Thirty-one samples could
      be genotyped by dot-blot showing the following results: G1 = 16, G4 = 6, G3 = 5,
      and G2 = 4. The data show circulation of genotypes G1-G4 and the predominance of
      G1. The knowledge of genotypes provides important information concerning
      rotavirus circulation in Central Brazil.

PMID- 11285458
TI  - Muscle sympathetic nerve activity and hemodynamic alterations in middle-aged
      obese women.
AB  - To study the relationship between the sympathetic nerve activity and hemodynamic
      alterations in obesity, we simultaneously measured muscle sympathetic nerve
      activity (MSNA), blood pressure, and forearm blood flow (FBF) in obese and lean
      individuals. Fifteen normotensive obese women (BMI = 32.5 +/- 0.5 kg/m2) and 11
      age-matched normotensive lean women (BMI = 22.7 +/- 1.0 kg/m2) were studied. MSNA
      was evaluated directly from the peroneal nerve by microneurography, FBF was
      measured by venous occlusion plethysmography, and blood pressure was measured
      noninvasively by an autonomic blood pressure cuff. MSNA was significantly
      increased in obese women when compared with lean control women. Forearm vascular
      resistance and blood pressure were significantly higher in obese women than in
      lean women. FBF was significantly lower in obese women. BMI was directly and
      significantly correlated with MSNA, blood pressure, and forearm vascular
      resistance levels, but inversely and significantly correlated with FBF levels.
      Obesity increases sympathetic nerve activity and muscle vascular resistance, and
      reduces muscle blood flow. These alterations, taken together, may explain the
      higher blood pressure levels in obese women when compared with lean age-matched
      women.

PMID- 11285459
TI  - Influence of dexamethasone and weight loss on the regulation of serum leptin
      levels in obese individuals.
AB  - The adipocyte hormone leptin is thought to serve as a signal to the central
      nervous system reflecting the status of fat stores. Serum leptin levels and
      adipocyte leptin messenger RNA levels are clearly increased in obesity.
      Nevertheless, the factors regulating leptin production are not fully understood.
      The aim of this study was to determine the effects of in vivo administration of
      the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels
      in two independent protocols. Twenty-five obese subjects were studied (18 women
      and 7 men, mean age 26.6 +/- 6 years, BMI 31.1 +/- 2.5 kg/m(2), %fat 40.3 +/-
      8.3) and compared at baseline to 22 healthy individuals. Serum levels of leptin,
      insulin, proinsulin and glucose were assessed at baseline and after ingestion of
      dexamethasone, 4 mg per day (2 mg, twice daily) for two consecutive days. To
      study the effects of weight loss on serum leptin, 17 of the obese subjects were
      submitted to a low-calorie dietary intervention trial for 8 weeks and again blood
      samples were collected. Serum leptin levels were significantly higher in the
      obese group compared to the control group and a high positive correlation between
      leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001). After
      dexamethasone, there was a significant increase in serum leptin levels (22.9 +/-
      12.3 vs 51.4 +/- 23.3 ng/ml, P<0.05). Weight loss (86.1 +/- 15.1 vs 80.6 +/- 14.2
      kg, P<0.05) led to a reduction in leptin levels (25.13 +/- 12.8 vs 15.9 +/- 9.1
      ng/ml, P<0.05). We conclude that serum leptin levels are primordially dependent
      on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent
      secretagogues of leptin in obese subjects and a mild fat mass reduction leads to
      a disproportionate decrease in serum leptin levels. This suggests that, in
      addition to the changes in fat mass, complex nutritional and hormonal
      interactions may also play an important role in the regulation of leptin levels.

PMID- 11285460
TI  - The Agamma-195 (C-->G) mutation in hereditary persistence of fetal hemoglobin is
      not associated with activation of a reporter gene in vitro.
AB  - Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in
      which the expression of gamma-globin genes persists into adult life. Several
      point mutations have been associated with the increased gamma-globin gene
      promoter activity. We evaluated the -195 (C-->G) mutation by a functional in
      vitro assay based on the luciferase reporter gene system. The results indicated
      that the increased promoter activity observed in vivo could not be reproduced in
      vitro under the conditions employed, suggesting that other factors may be
      involved in the overexpression of the gamma-globin gene containing the -195 (C-
      >G) mutation. Furthermore, this is the first time that the -195 (C-->G) mutation
      of the Agamma-globin gene has been evaluated by in vitro gene expression.

PMID- 11285461
TI  - Relative influence of age, resting heart rate and sedentary life style in short
      term analysis of heart rate variability.
AB  - In order to assess the relative influence of age, resting heart rate (HR) and
      sedentary life style, heart rate variability (HRV) was studied in two different
      groups. The young group (YG) consisted of 9 sedentary subjects aged 15 to 20
      years (YG-S) and of 9 nonsedentary volunteers (YG-NS) also aged 15 to 20. The
      elderly sedentary group (ESG) consisted of 16 sedentary subjects aged 39 to 82
      years. HRV was assessed using a short-term procedure (5 min). R-R variability was
      calculated in the time-domain by means of the root mean square successive
      differences. Frequency-domain HRV was evaluated by power spectrum analysis
      considering high frequency and low frequency bands. In the YG the effort
      tolerance was ranked in a bicycle stress test. HR was similar for both groups
      while ESG showed a reduced HRV compared with YG. Within each group, HRV displayed
      a negative correlation with HR. Although YG-NS had better effort tolerance than
      YG-S, their HR and HRV were not significantly different. We conclude that HRV is
      reduced with increasing HR or age, regardless of life style. The results obtained
      in our short-term study agree with others of longer duration by showing that age
      and HR are the main determinants of HRV. Our results do not support the idea that
      changes in HRV are related to regular physical activity.

PMID- 11285462
TI  - Incorporation of dietary trans monounsaturated fatty acids into tissues of Walker
      256 tumor-bearing rats.
AB  - The correlation between dietary trans fatty acids and neoplasia was examined in
      the present study. Walker 256 tumor-bearing and control rats were fed a trans
      monounsaturated fatty acid (MUFA)-rich diet for 8 weeks and the incorporation of
      trans fatty acids by tumor tissue was examined. Also, the effect of tumor growth
      on trans fatty acid composition of plasma and liver, and the content of
      thiobarbituric acid-reactive substances (TBARS) was determined. Walker 256 tumor
      cells presented both trans and cis MUFAs given in the diet. The equivalent diet
      proportions were 0.66 for trans and 1.14 for cis. Taking into consideration the
      proportion of trans MUFAs in plasma (11.47%), the tumor incorporated these fatty
      acids in a more efficient manner (18.27%) than the liver (9.34%). Therefore, the
      dietary trans fatty acids present in the diet are actively incorporated by the
      tumor. Tumor growth itself caused marked changes in the proportion of
      polyunsaturated fatty acids in the plasma and liver but provoked only slight
      modifications in both trans and cis MUFAs. Tumor growth also reduced the
      unsaturation index in both plasma and liver, from 97.79 to 86.83 and from 77.51
      to 69.64, respectively. This effect was partially related to an increase in the
      occurrence of the lipid oxidation/peroxidation process of TBARS content which was
      increased in both plasma (from 0.428 to 0.505) and liver (from 9.425 to 127.792)
      due to tumor growth.

PMID- 11285463
TI  - Acute and chronic effects of cadmium on blood homeostasis of an estuarine crab,
      Chasmagnathus granulata, and the modifying effect of salinity.
AB  - Whole body oxygen consumption and some hemolymph parameters such as pH, partial
      pressure of gases, level of ions and lactate were measured in the estuarine crab
      Chasmagnathus granulata after both acute (96 h) and chronic (2 weeks) exposure to
      cadmium at concentrations ranging from 0.4 to 6.3 mg/l. In all instances, the
      crabs developed hemolymph acidosis, but no respiratory (increased PCO2) or
      lactate increases were evident. Hemolymph levels of sodium and calcium were
      always increased by cadmium exposure. The chronic toxicity of cadmium was
      enhanced at 12 per mil salinity, even causing a significantly higher mortality in
      comparison with the higher salinity (30 per mil ) used. A general metabolic
      arrest took place at 12 per mil salinity in the crabs chronically exposed to
      cadmium, as indicated by decreases of oxygen consumption and PCO2, an increase of
      PO2, along with no changes in lactate levels. These imbalances were associated
      with severe necrosis and telangiectasia in the respiratory gills, probably
      leading to respiratory impairment and finally histotoxic hypoxia and death of the
      animals.

PMID- 11285464
TI  - Effect of sodium carboxymethylcellulose and methylprednisolone on the healing of
      jejunal anastomoses in rats.
AB  - Sodium carboxymethylcellulose (SCMC) has been effective in reducing adhesion
      formation and corticosteroids reduce the inflammatory process. The objective of
      this study was to define the intraperitoneal (ip) effects of SCMC combined with
      intramuscular (im) methylprednisolone on peritoneal adhesion formation and on
      jejunal anastomosis healing in rats. Twenty Wistar rats (200-350 g) were divided
      into four groups (N = 5): groups I and III (controls) 5 and 21 days of treatment
      before sacrifice, respectively; groups II and IV (experimental groups) 5 and 21
      days of treatment, respectively. SCMC (1%) was infused into the abdominal cavity
      and methylprednisolone (10 mg kg-1 day-1) was injected im daily from the day
      before surgery for animals of groups II and IV. All rats were submitted to a
      jejunal anastomosis. Sections of the anastomosis were prepared for routine
      histopathological analysis. The abdominal adhesion of group IV was less intense
      when compared with group III (P<0.0008). Anastomotic resistance was higher in
      groups II and IV when compared with groups I and III, respectively (P<0.05).
      There was no histological difference between groups I and II (exuberant
      granulation tissue on the serosal surface). Group III presented little peritoneal
      fibrinous tissue, with numerous thick collagen fibers. Group IV presented
      extensive although immature young fibrous tissue with rare thick collagen fibers.
      Sodium carboxymethylcellulose combined with corticosteroids seemed to diminish
      peritoneal adhesion but did not reduce anastomotic resistance.

PMID- 11285465
TI  - Association between EcoRI fragment-length polymorphism of the immunoglobulin
      lambda variable 8 (IGLV8) gene family with rheumatoid arthritis and systemic
      lupus erythematosus.
AB  - The human immunoglobulin lambda variable 8 (IGLV8) subgroup is a gene family
      containing three members, one of them included in a monomorphic 3.7-kb EcoRI
      genomic fragment located at the major lambda variable locus on chromosome 22q11.1
      (gene IGLV8a, EMBL accession No. Z73650) at 100% frequency in the normal urban
      population. The second is a polymorphic RFLP allele included in a 6.0-kb EcoRI
      fragment at 10% frequency, and the third is located in a monomorphic 8.0-kb EcoRI
      fragment at 100% frequency, the last being translocated to chromosome 8q11.2 and
      considered to be an orphan gene. Our Southern blot-EcoRI-RFLP studies in normal
      individuals and in patients with rheumatoid arthritis (RA) or with systemic lupus
      erythematosus (SLE), using a specific probe for the IGLV8 gene family (probe
      pVL8, EMBL accession No. X75424), have revealed the two monomorphic genomic
      fragments containing the IGLV8 genes, i.e., the 3.7-kb fragment from chromosome
      22q11.1 and the 8.0-kb fragment from 8q11.2, both occurring at 100% frequency
      (103 normal individuals, 48 RA and 28 SLE patients analyzed), but absence of the
      6.0-kb IGLV8 polymorphic RFLP allele in all RA or SLE patients. As expected, the
      frequency of the 6.0-kb allele among the normal individuals was 10%. These
      findings suggest an association between the absence of the 6.0-kb EcoRI fragment
      and rheumatoid arthritis and systemic lupus erythematosus.

PMID- 11285466
TI  - The low efficiency of dendritic cells and macrophages from mice susceptible to
      Paracoccidioides brasiliensis in inducing a Th1 response.
AB  - In the present study we evaluated T cell proliferation and Th lymphokine patterns
      in response to gp43 from Paracoccidioides brasiliensis presented by isolated
      dendritic cells from susceptible and resistant mice. T cell proliferation assays
      showed that dendritic cells from susceptible mice were less efficient than those
      from resistant mice. The pattern of T cell lymphokines stimulated by dendritic
      cells was always Th1, although the levels of IL-2 and IFN-gamma were lower in T
      cell cultures from susceptible mice. To determine whether different antigen
      presenting cells such as macrophages and dendritic cells stimulated different
      concentrations of Th1 lymphokines, the production of IFN-gamma and IL-2 was
      measured. It was observed that dendritic cells were more efficient than
      macrophages in stimulating lymphoproliferation in resistant mice. However, no
      significant difference was observed for IFN-gamma or IL-2 production. When cells
      from susceptible mice were used, macrophages were more efficient in stimulating
      lymphoproliferation than dendritic cells, but no difference was observed in the
      production of Th1 cytokine. Taken together, these results suggest the lower
      efficiency of dendritic cells and macrophages from B10.A mice in stimulating T
      cells that secrete Th1 lymphokines in vitro, an effect that may be involved in
      the progression of the disease in vivo.

PMID- 11285467
TI  - Detection of immunoglobulin G in the lung and liver of hamsters with visceral
      leishmaniasis.
AB  - Several organs are affected in visceral leishmaniasis, not only those rich in
      mononuclear phagocytes. Hypergammaglobulinemia occurs during visceral
      leishmaniasis; anti-Leishmania antibodies are not primarily important for
      protection but might be involved in the pathogenesis of tissue lesions. The
      glomerulonephritis occurring in visceral leishmaniasis has been attributed to
      immune complex deposition but in other organs the mechanism has not been studied.
      In the current study we demonstrated the presence of IgG in the lung and liver of
      hamsters with visceral leishmaniasis. Hamsters were injected intraperitoneally
      with 2 x 10(7) amastigotes of Leishmania (Leishmania) chagasi and the presence of
      IgG in the liver and lung was evaluated at 7, 15, 30, 45, 80 and 102 days
      postinfection (PI) by immunohistochemistry. The parasite burden in the spleen and
      liver increased progressively during infection. We observed a deposit of IgG from
      day 7 PI that increased progressively until it reached highest intensity around
      30 and 45 days PI, declining at later times. The IgG deposits outlined the
      sinusoids. In the lung a deposit of IgG was observed in the capillary walls that
      was moderate at day 7 PI, but the intensity increased remarkably at day 30 PI and
      declined at later times of infection. No significant C3 deposits were observed in
      the lung or in the liver. We conclude that IgG may participate in the
      pathogenesis of the inflammatory process of the lung and liver occurring in
      experimental visceral leishmaniasis and we discuss an alternative mechanism other
      than immune complex deposition.

PMID- 11285468
TI  - Interference of propylene glycol with the hole-board test.
AB  - Experimental drugs and/or plant extracts are often dissolved in solvents,
      including propylene glycol. Nevertheless, there is evidence for psychoactive
      properties of this alcohol. In this study we found that in the hole-board test
      10% propylene glycol did not modify the head-dipping behavior. However, 30%
      propylene glycol induced an increase in the number of head-dips (46.92 +/- 2.37
      compared to 33.83 +/- 4.39, P<0.05, ANOVA/Student-Newman-Keuls), an effect
      comparable to that obtained with 0.5 mg/kg diazepam (from 33.83 +/- 4.39 to 54 +/
      3.8, P<0.01, ANOVA/Student-Newman-Keuls). These results demonstrate that 30%
      propylene glycol has significant anxiolytic effects in this model and therefore
      cannot be used as an innocuous solvent.

PMID- 11285469
TI  - Antagonism by hemoglobin of effects induced by L-arginine in neuromuscular
      preparations from rats.
AB  - Nitric oxide (NO)-synthase is present in diaphragm, phrenic nerve and vascular
      smooth muscle. It has been shown that the NO precursor L-arginine (L-Arg) at the
      presynaptic level increases the amplitude of muscular contraction (AMC) and
      induces tetanic fade when the muscle is indirectly stimulated at low and high
      frequencies, respectively. However, the precursor in muscle reduces AMC and
      maximal tetanic fade when the preparations are stimulated directly. In the
      present study the importance of NO synthesized in different tissues for the L-Arg
      induced neuromuscular effects was investigated. Hemoglobin (50 nM) did not
      produce any neuromuscular effect, but antagonized the increase in AMC and tetanic
      fade induced by L-Arg (9.4 mM) in rat phrenic nerve-diaphragm preparations. D-Arg
      (9.4 mM) did not produce any effect when preparations were stimulated indirectly
      at low or high frequency. Hemoglobin did not inhibit the decrease of AMC or the
      reduction in maximal tetanic tension induced by L-Arg in preparations previously
      paralyzed with d-tubocurarine and directly stimulated. Since only the presynaptic
      effects induced by L-Arg were antagonized by hemoglobin, the present results
      suggest that NO synthesized in muscle acts on nerve and skeletal muscle.
      Nevertheless, NO produced in nerve and vascular smooth muscle does not seem to
      act on skeletal muscle.

PMID- 11285470
TI  - Vertical human immunodeficiency virus type 1--HIV-1--transmission--a review.
AB  - Several factors appear to affect vertical HIV-1 transmission, dependent mainly on
      characteristics of the mother (extent of immunodeficiency, co-infections, risk
      behaviour, nutritional status, immune response, genetical make-up), but also of
      the virus (phenotype, tropism) and, possibly, of the child (genetical make-up).
      This complex situation is compounded by the fact that the virus may have the
      whole gestation period, apart from variable periods between membrane rupture and
      birth and the breast-feeding period, to pass from the mother to the infant. It
      seems probable that an extensive interplay of all factors occurs, and that some
      factors may be more important during specific periods and other factors in other
      periods. Factors predominant in protection against in utero transmission may be
      less important for peri-natal transmission, and probably quite different from
      those that predominantly affect transmission by mothers milk. For instance,
      cytotoxic T lymphocytes will probably be unable to exert any effect during breast
      feeding, while neutralizing antibodies will be unable to protect transmission by
      HIV transmitted through infected cells. Furthermore, some responses may be
      capable of controlling transmission of determined virus types, while being
      inadequate for controlling others. As occurrence of mixed infections and
      recombination of HIV-1 types is a known fact, it does not appear possible to
      prevent vertical HIV-1 transmission by reinforcing just one of the factors, and
      probably a general strategy including all known factors must be used. Recent
      reports have brought information on vertical HIV-1 transmission in a variety of
      research fields, which will have to be considered in conjunction as background
      for specific studies.

PMID- 11285471
TI  - Cutaneous leishmaniasis caused by members of Leishmania braziliensis complex in
      Nayarit, State of Mexico.
AB  - An epidemiological study was carried out in the northern Mexican state, Nayarit.
      Fourteen patients with possible cutaneous leishmaniasis skin lesions gave
      positive Montenegro skin tests. Biopsies were taken from the skin ulcer and
      analyzed by polymerase chain reaction (PCR) with specific primers for the
      Leishmania mexicana complex; however all biopsies were not amplified. PCR carried
      out with specific primers for the L. braziliensis complex resulted in the
      amplification of all patient DNA. DNA from 12 out of 14 biopsies gave positive
      amplification with primers species specific for L. (Viannia) braziliensis and
      hybridized with a species specific L. (V.) braziliensis probe. These results
      demonstrate the presence in Nayarit of at least two members of the L.
      braziliensis complex. Most of the cutaneous lesions were caused by L. (V.)
      braziliensis and two by another species belonging to the L. braziliensis complex.
      As far as we are aware, this is the first report of L. (V.) braziliensis in
      Nayarit. The main risk factor associated with the contraction of this disease in
      Nayarit is attributed to working on coffee plantations.

PMID- 11285472
TI  - Prevalence of human immunodeficiency virus infection in alcoholics.
AB  - To verify the prevalence of infection by human immunodeficiency virus (HIV) in
      alcoholics we studied 131 alcoholic patients (119 males and 12 females) with a
      mean age of 44.3 +/- 10.8 years. Serum samples were collected from this group and
      analysed, by ELISA, for antibodies against HIV as well as for serological markers
      for hepatitis B virus (HBV) and hepatitis C virus (HCV). As we have previously
      described, we found a high prevalence of HBV (26.4%) and HCV (4.2%) markers as
      compared to the prevalence of these markers in samples of normal blood donors
      from Uberlandia's Hemocentro Regional, which are 4% and 0.4%, respectively. Of
      the 131 patients, four (3%) had antibodies against HIV, three (75%) of which were
      injecting drug users (IDU). In the HIV-negative group, only one patient was an
      IDU. The prevalence of HIV in our population, according to data from the city's
      Health Secretary, varies from 3.1% to 6.2%. We conclude that, at least for the
      moment, alcoholism per se, did not constitute an important risk factor for HIV
      infection. However, acquired immunodeficiency syndrome is a rather recent disease
      as compared to hepatitis B and C and, as the transmission routes are similar for
      HIV and hepatitis viruses, an increase in the incidence of HIV infection in
      alcoholics may be just a question of time.

PMID- 11285473
TI  - Hepatitis E virus infection in selected Brazilian populations.
AB  - A retrospective study on the prevalence of hepatitis E virus (HEV) infection was
      conducted in selected populations in Rio de Janeiro, Brazil. A total of 1,115
      subjects were tested including 146 patients with acute Non-A Non-B Non-C (NANBNC)
      viral hepatitis, 65 hemodialysis patients, 93 blood donors, 102 intravenous drug
      users (IVDUs), 304 pregnant women, 145 individuals living in the rural area and
      260 individuals living in the urban area. In order to characterize a favorable
      epidemiological set for enterically transmitted infection in the studied
      populations we also evaluated the prevalence of anti-HAV IgG (hepatitis A virus)
      antibodies. Specific antibodies to HEV (anti-HEV IgG) were detected by a
      commercial EIA and specific antibodies to HAV (anti-HAV IgG) were detected using
      a competitive "in house" EIA. We found a high prevalence of anti-HAV IgG in these
      populations, that could indicate some risk for infections transmitted via the
      fecal-oral route. The anti-HEV IgG prevalence among the different groups were:
      2.1% in patients with acute NANBNC viral hepatitis, 6.2% in hemodialysis
      patients, 4.3% in blood donors, 11.8% in IVDUs, 1% in pregnant women, and 2.1% in
      individuals form the rural area. Among individuals living in the urban area we
      did not find a single positive serum sample. Our results demonstrated the
      presence of anti-HEV IgG in almost all studied populations; however, further
      studies are necessary to establish the real situation of HEV epidemiology in Rio
      de Janeiro, Brazil.

PMID- 11285474
TI  - Population genetic analysis of Colombian Trypanosoma cruzi isolates revealed by
      enzyme electrophoretic profiles.
AB  - Although Colombia presents an enormous biological diversity, few studies have
      been conducted on the population genetics of Trypanosoma cruzi. This study was
      carried out with 23 Colombian stocks of this protozoa analyzed for 13
      isoenzymatic loci. The Hardy-Weinberg equilibrium, the genetic diversity and
      heterogeneity, the genetic relationships and the possible spatial structure of
      these 23 Colombian stocks of T. cruzi were estimated. The majority of results
      obtained are in agreement with a clonal population structure. Nevertheless, two
      aspects expected in a clonal structure were not discovered in the Colombian T.
      cruzi stocks. There was an absence of given zymodemes over-represented from a
      geographical point of view and the presumed temporal stabilizing selective
      phenomena was not observed either in the Colombian stocks sampled several times
      through the years of the study. Some hypotheses are discussed in order to explain
      the results found.

PMID- 11285475
TI  - Biological characterization of Trypanosoma cruzi strains.
AB  - Biological parameters of five Trypanosoma cruzi strains from different sources
      were determined in order to know the laboratory behaviour of natural populations.
      The parameters evaluated were growth kinetics of epimastigotes, differentiation
      into metacyclic forms, infectivity in mammalian cells grown in vitro and parasite
      susceptibility to nifurtimox, benznidazole and gentian violet. Differences in
      transformation to metacyclic, in the percentage of infected cells as well as in
      the number of amastigotes per cell were observed among the strains. Regarding to
      pharmacological assays, Y strain was the most sensitive to the three assayed
      compounds. These data demonstrate the heterogeneity of natural populations of T.
      cruzi, the only responsible of infection in humans.

PMID- 11285476
TI  - Ultrastructure of spermatogenesis and sperm development in Saccocoelioides godoyi
      Kohn & Froes, 1986 (Digenea, Haploporidae).
AB  - Ultrastructural observations of spermatogenesis and sperm development of
      Saccocoelioides godoyi, an intestinal parasite of Leporinus friderici (Bloch,
      1794) are described. The irregular-shaped spermatogonia form a peripheral layer,
      and show a prominent nucleus. Spermatocytes are larger than spermatogonia, and in
      the early stage present synaptonemal complex. Spermatids show nuclei smaller than
      the spermatocytes. Spermiogenesis is characterized by outgrowth of the zone of
      differentiation, presenting basal bodies, separated by an intercentriolar body.
      At the end of this process, the spermatozoa are released into the residual
      cytoplasmic mass. The spermatozoa of S. godoyi are elongate, similar to the
      pattern described for other Digenea, showing nuclei, mitochondria and two
      axonemes with the 9+1 configuration. The peripheral cortical microtubules on the
      dorsal and ventral faces are laterally interrupted.

PMID- 11285477
TI  - [A new species of the oliveirai complex (new designation for matogrossensis
      complex) from the State of Rio Grande do Sul, Brazil].
AB  - The authors describe a new species of Triatominae (Hemiptera, Reduviidae) from
      the State of Rio Grande do Sul, Brazil. The study was made with specimens
      captured in basaltic formations, at an average altitude of 750 m.o.s.l. The new
      species is included in the oliveirai complex together with other four species T.
      williami, T. matogrossensis, T. guazu and T. jurbergi). The new species was
      compared with the most similar one, T. oliveirai, from which the main differences
      are on the proportions of head, ante and postocular regions, the general color
      pattern and the male genitalia, specially on the median process of the pygophore,
      the support of phallosome, the vesica and the process of the endosome.

PMID- 11285478
TI  - Nematodes of elasmobranch fishes from the southern coast of Brazil.
AB  - New records for nematode species recovered from elasmobranch fishes in Brazil are
      established and new systematical arrangements proposed. Parascarophis sphyrnae
      Campana-Rouget, 1955 from the spiral valve of Sphyrna zygaena is referred for the
      first time in South America as a new host record. Procamallanus (S.) pereirai
      Annereaux, 1946, from the spiral valve of Raja castelnaui is reported
      parasitizing an elasmobranch host. Nematode larvae of the genera Anisakis,
      Contracaecum, Pseudoterranova and Raphidascaris are listed from the stomach and
      spiral valves of several hosts. Anisakidae larvae previously referred in Brazil
      in the genus Phocanema should be reallocated in Pseudoterranova. Nematodes of the
      genera Anisakis, Contracaecum, Pseudoterranova and Raphidascaris are reported for
      the first time parasitizing elasmobranchs in Brazil.

PMID- 11285479
TI  - Immunochemotherapy in American cutaneous leishmaniasis: immunological aspects
      before and after treatment.
AB  - In this study, we evaluated the immune response of patients suffering from
      cutaneous leishmaniasis treated with two distinct protocols. One group was
      treated with conventional chemotherapy using pentavalent antimonium salts and the
      other with immunochemotherapy where a vaccine against cutaneous leishmaniasis was
      combined with the antimonium salt. Our results show that, although no differences
      were observed in the necessary time for complete healing of the lesions between
      the two treatments, peripheral blood mononuclear cells from patients treated by
      chemotherapy showed smaller lymphoproliferative responses at the end of the
      treatment than those from patients in the immunochemotherapy group. Furthermore,
      IFN-gamma production was also different between the two groups. While cells from
      patients in the chemotherapy group produced more IFN-gamma at the end of
      treatment, a significant decrease in this cytokine production was associated with
      healing in the immunochemotherapy group. In addition, IL-10 production was also
      less intense in this latter group. Finally, an increase in CD8+ -IFN-gamma
      producing cells was detected in the chemotherapy group. Together these results
      point to an alternative treatment protocol where healing can be induced with a
      decreased production of a potentially toxic cytokine.

PMID- 11285480
TI  - Vertical toxoplasmosis in a murine model. Protection after immunization with
      antigens of Toxoplasma gondii incorporated into liposomes.
AB  - Distinct Toxoplasma gondii antigens were entrapped within liposomes and evaluated
      for their ability to protect Balb/c mice against congenital transmission: soluble
      tachyzoite antigen (L/STAg), soluble tissue cyst antigen (L/SCAg), soluble
      tachyzoite plus tissue cyst (L/STCAg) or purified 32kDa antigen of tachyzoite
      (L/pTAg). Soluble tachyzoite antigen alone in PBS (STAg) or emulsified in
      Freund's Complete Adjuvant (FCA/STAg) was also evaluated. Dams were inoculated
      subcutaneously with these antigens 6, 4 and 2 weeks prior to a challenge with
      four tissue cysts of the P strain of T. gondii orally between 10 and 14 days of
      pregnancy. Significant diminution differences were observed between the frequency
      of infected pups born of the dams immunized with the antigens incorporated into
      liposomes and that of pups born of the dams immunized with antigen emulsified in
      FCA or non immunized group (p<0.05). There was a significant decrease in the
      number of pups born dead in the groups L/STAg, L/SCAg and L/pTAg when compared
      with pups from all other groups (p <0.05). All dams immunized with or without
      adjuvant showed an antibody response and a proliferation of T-cells. However, no
      correlation was found between immune response and protection against the
      challenge.

PMID- 11285481
TI  - Characterization of constitutive and putative differentially expressed mRNAs by
      means of expressed sequence tags, differential display reverse transcriptase-PCR
      and randomly amplified polymorphic DNA-PCR from the sand fly vector Lutzomyia
      longipalpis.
AB  - Molecular studies of insect disease vectors are of paramount importance for
      understanding parasite-vector relationship. Advances in this area have led to
      important findings regarding changes in vectors' physiology upon blood feeding
      and parasite infection. Mechanisms for interfering with the vectorial capacity of
      insects responsible for the transmission of diseases such as malaria, Chagas
      disease and dengue fever are being devised with the ultimate goal of developing
      transgenic insects. A primary necessity for this goal is information on gene
      expression and control in the target insect. Our group is investigating molecular
      aspects of the interaction between Leishmania parasites and Lutzomyia sand flies.
      As an initial step in our studies we have used random sequencing of cDNA clones
      from two expression libraries made from head/thorax and abdomen of sugar fed L.
      longipalpis for the identification of expressed sequence tags (EST). We applied
      differential display reverse transcriptase-PCR and randomly amplified polymorphic
      DNA-PCR to characterize differentially expressed mRNA from sugar and blood fed
      insects, and, in one case, from a L. (V.) braziliensis-infected L. longipalpis.
      We identified 37 cDNAs that have shown homology to known sequences from GeneBank.
      Of these, 32 cDNAs code for constitutive proteins such as zinc finger protein,
      glutamine synthetase, G binding protein, ubiquitin conjugating enzyme. Three are
      putative differentially expressed cDNAs from blood fed and Leishmania-infected
      midgut, a chitinase, a V-ATPase and a MAP kinase. Finally, two sequences are
      homologous to Drosophila melanogaster gene products recently discovered through
      the Drosophila genome initiative.

PMID- 11285482
TI  - Molecular karyotype and chromosomal localization of genes encoding beta-tubulin,
      cysteine proteinase, hsp 70 and actin in Trypanosoma rangeli.
AB  - The molecular karyotype of nine Trypanosoma rangeli strains was analyzed by
      contour-clamped homogeneous electric field electrophoresis, followed by the
      chromosomal localization of beta-tubulin, cysteine proteinase, 70 kDa heat shock
      protein (hsp 70) and actin genes. The T. rangeli strains were isolated from
      either insects or mammals from El Salvador, Honduras, Venezuela, Colombia, Panama
      and southern Brazil. Also, T. cruzi CL-Brener clone was included for comparison.
      Despite the great similarity observed among strains from Brazil, the molecular
      karyotype of all T. rangeli strains analyzed revealed extensive chromosome
      polymorphism. In addition, it was possible to distinguish T. rangeli from T.
      cruzi by the chromosomal DNA electrophoresis pattern. The localization of beta
      tubulin genes revealed differences among T. rangeli strains and confirmed the
      similarity between the isolates from Brazil. Hybridization assays using probes
      directed to the cysteine proteinase, hsp 70 and actin genes discriminated T.
      rangeli from T. cruzi, proving that these genes are useful molecular markers for
      the differential diagnosis between these two species. Numerical analysis based on
      the molecular karyotype data revealed a high degree of polymorphism among T.
      rangeli strains isolated from southern Brazil and strains isolated from Central
      and the northern South America. The T. cruzi reference strain was not clustered
      with any T. rangeli strain.

PMID- 11285484
TI  - Life cycle and reproductive parameters of Clerada apicicornis signoret
      (Hemiptera: Lygaeidae) under laboratory conditions.
AB  - The life cycle of Clerada apicicornis was determined under laboratory conditions.
      Mean development times in days were: egg 27.2, nymph I 12.5, nymph II 12, nymph
      III 13.4, nymph IV 16.4, nymph V 26. The life expectancy of adults ranged from
      117 to 317 days (mean 196 days). Based on a cohort of 29 females of C.
      apicicornis, a horizontal life table was constructed. The following predictive
      parameters were obtained: net rate of reproduction (Ro = 48.31), intrinsic rate
      of population increase (r(m) = 0.153), generation time (Tc = 28.20 weeks), and
      finite rate of population increment (lambda = 1.16). The reproductive value (Vx)
      for each age class of the cohort females was calculated. The following observed
      parameters were calculated after mortality in each stage: net rate of
      reproduction (R'o=13.4), intrinsic rate of population increase (r c' =0.09 ), and
      finite rate of population increment (lambda' =1.1). The generation time (Tc'
      =27.4) was estimated using the methods of Laughlin and Bengstron. A vertical life
      table was elaborated and mortality was described for one generation of the
      cohort.

PMID- 11285483
TI  - The molluscicidal activity of the latex of Euphorbia splendens var. hislopii on
      Melanoides tuberculata (Thiaridae), a snail associated with habitats of
      Biomphalaria glabrata (Planorbidae).
AB  - The use of the latex of Euphorbia splendens var. hislopii was considered as an
      effective control method for Biomphalaria glabrata in Sumidouro, Rio de Janeiro.
      However, the appearance and expansion of the snail Melanoides tuberculata since
      August 1997, with the concomitant reduction of the population of B. glabrata
      suggest that competitive exclusion might be taking place. Depending on the
      susceptibility of the thiarid to the E. splendens toxin, the natural control that
      is occurring could be interrupted by the employment of the latex if the planorbid
      were less susceptible to the toxin. The aim of this study is to investigate the
      molluscicidal activity of the latex on M. tuberculata. We used 420 M.
      tuberculata, from Sumidouro. Fourteen different latex concentrations were tested
      using World Health Organization general methodology. Probit analysis was used for
      LD90 and LD50 determination. The LD50 was 3.57 mg/l and LD90 was 6.22 mg/l. At
      the highest concentration (10 mg/l) there was no survival. No significant
      differences among replicas (chi2 = 8.31; gl = 13; p > 0.05) were found. The LD90
      dose for M. tuberculata was 13.8 times greater than that for B. glabrata, so that
      the molluscicide in the presence of the thiarid may have a synergic effect on
      reduction of Biomphalaria populations.

PMID- 11285485
TI  - Worm burdens in outbred and inbred laboratory rats with morphometric data on
      Syphacia muris (Yamaguti, 1935) Yamaguti, 1941 (Nematoda, Oxyuroidea).
AB  - Syphacia muris worm burdens were evaluated in the rat Rattus norvegicus of the
      strains Wistar (outbred), Low/M and AM/2/Torr (inbred), maintained conventionally
      in institutional animal houses in Brazil. Morphometrics and illustration data for
      S. muris recovered from Brazilian laboratory rats are provided for the first time
      since its proposition in 1935.

PMID- 11285486
TI  - [Flight initiation in Triatoma infestans and T. melanosoma (Hemiptera,
      Reduviidae)].
AB  - The flight initiation of T. infestans, the main vector of Chagas disease in the
      Southern Cone countries of Latin America, and of the closely-related species T.
      melanosoma was studied in laboratory. The results demonstrated that after the
      beginning of observations the peak of the flight activity was about 14 days after
      feeding in both species and it was usually more marked in the females than in the
      males, but there were no significant differences in the flight behaviour of the
      two species.

PMID- 11285487
TI  - Role of two Triatoma (Hemiptera: Reduviidae: Triatominae) species in the
      transmission of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) to man in
      the west coast of Mexico.
AB  - From August 1997 to August 1998, 334 specimens of Triatoma longipennis and 62 of
      T. picturata were collected in four groups of localities placed in the zone from
      Guadalajara, Jalisco to Tepic, Nayarit, in the West Coast of Mexico. Most T.
      longipennis were collected outdoors (69.2%) while most T. picturata (58.1%) were
      collected indoors. All collected specimens were examined for Trypanosoma cruzi
      infection, which was detected on 98 (29.3%) T. longipennis and 17 (27.4%) T.
      picturata. This study confirms the role of T. longipennis and T. picturata as
      some of the main T. cruzi vectors to humans in Mexico. Habitation Infestation
      Rate with T. longipennis was of 0.09 and with T. picturata was of 0.03 and the
      predominating ecotopes were pile of blocks, chicken coops, pigsties, wall crawls
      and beds.

PMID- 11285488
TI  - Community ecology of the metazoan parasites of white croaker, Micropogonias
      furnieri (Osteichthyes: Sciaenidae), from the coastal zone of the State of Rio de
      Janeiro, Brazil.
AB  - One hundred specimens of white croakers, Micropogonias furnieri (Desmarest 1823)
      (Osteichthyes: Sciaenidae) collected from Pedra de Guaratiba (23 degrees 01'S, 43
      degrees 38'W), State of Rio de Janeiro, Brazil, from September 1997 to August
      1999, were necropsied to study their parasites. The majority of the fish (95%)
      were parasitized by metazoan. Twenty-eight species of parasites were collected.
      The nematodes were the 40.5% of the total number of parasites specimens
      collected. Dichelyne elongatus was the most dominant species. Lobatostoma
      ringens, Pterinotrematoides mexicanum, Corynosoma australe, D. elongatus, and
      Caligus haemulonis showed a positive correlation between the host's total length
      and parasite prevalence and abundance. The monogenean P. mexicanum had
      differences in the prevalence and abundance in relation to sex of the host. The
      mean diversity in the infracommunities of M. furnieri was H=0.499+/-0.411, with
      correlation with the host's total length and without differences in relation to
      sex of the host. One pair of ectoparasites showed positive covariation, and two
      pairs of endoparasites showed positive association and covariation between their
      prevalences and abundances, respectively. Negative association or covariations
      were not found. The dominance of endoparasites in the croakers parasite
      infracommunities reinforced the differences found in sciaenids from the South
      American Pacific Ocean, in which the ectoparasites are dominant.

PMID- 11285489
TI  - Respiratory syncytial virus groups A and B in Porto Alegre, Brazil, from 1990 to
      1995 and 1998.
AB  - We analyzed the respiratory syncytial virus (RSV) groups and their
      epidemiological pattern that were detected over the course of seven years in
      southern Brazil. The two RSV groups co-circulated each year, but frequencies of
      groups A and B varied both between and within yearly outbreaks. In 1991, group A
      predominated over group B (p=0.0016). RSV outbreaks analyzed showed a temperature
      dependent pattern and no association with rainfall, similarly to other countries
      from southern South America. Knowledge of the variants is important in terms of
      both diagnosis and definition of a vaccine composition.

PMID- 11285490
TI  - Domestic and peridomestic transmission of American cutaneous leishmaniasis:
      changing epidemiological patterns present new control opportunities.
AB  - Predictions that deforestation would reduce American cutaneous leishmaniasis
      incidence have proved incorrect. Presentations at a recent international
      workshop, instead, demonstrated frequent domestication of transmission throughout
      Latin America. While posing new threats, this process also increases the
      effectiveness of vector control in and around houses. New approaches for sand fly
      control and effective targeting of resources are reviewed.

PMID- 11285491
TI  - Clinical picture of cutaneous leishmaniases due to Leishmania (Leishmania)
      mexicana in the Yucatan peninsula, Mexico.
AB  - Localized cutaneous leishmaniasis (LCL), known as "chiclero's ulcer" in southeast
      Mexico, was described by Seidelin in 1912. Since then, the sylvatic region of the
      Yucatan peninsula has been identified as an endemic focus of LCL. The purpose of
      the present work was to describe the clinical picture of LCL caused by Leishmania
      (Leishmania) mexicana in the Yucatan peninsula. A total of 136 cases of LCL,
      based on isolation and characterization of L. (L.) mexicana by isoenzymes and/or
      monoclonal antibodies, were selected. Some variability of clinical features
      regarding number, type, size, form, location and time of evolution of the lesions
      was observed. The most frequently observed presentation was a single, ulcerated,
      rounded small lesion, located on the ear, with an evolution time of less than
      three months, with neither cutaneous metastases nor lymphatic nor mucosal
      involvement. This picture corresponds to previous studies carried out in the same
      endemic area where an organism of the L. mexicana complex has been incriminated
      as a major aetiological agent of classical "chiclero's ulcer", confirming that in
      the Yucatan peninsula LCL due to L. (L.) mexicana when located on the pinna of
      the ear is a remarkable characteristic.

PMID- 11285492
TI  - Prevalence, species differentiation, haemolytic activity, and antibiotic
      susceptibility of aeromonads in untreated well water.
AB  - The use of untreated water for drinking and other activities have been associated
      with intestinal and extraintestinal infections in humans due to Aeromonas
      species. In the present study aeromonads were isolated from 48.7% of 1,000 water
      samples obtained from wells and other miscellaneous sources. Aeromonas species
      were detected in 45% of samples tested in spring, 34.5% in summer, 48% in autumn
      and 60% of samples tested in winter. Speciation of 382 strains resulted in 225
      (59%) being A. hydrophila, 103 (27%) A. caviae, 42 (11%) A. sobria and 11 (3%)
      atypical aeromonads. Of 171 Aeromonas strains tested for their haemolytic
      activity, 53%, 49%, 40% and 37% were positive in this assay using human, horse,
      sheep and camel erythrocytes respectively. The results obtained indicate that
      potentially enteropathogenic Aeromonas species are commonly present in untreated
      drinking water obtained from wells in Libya (this may also apply to other
      neighbouring countries) which may pose a health problem to users of such water
      supplies. In addition, ceftriaxone and ciprofloxacin are suitable drugs that can
      be used in the treatment of Aeromonas-associated infections, particularly in the
      immunocompromised, resulting from contact with untreated sources of water.

PMID- 11285493
TI  - Prevalence and intensity of Haemoproteus columbae in three species of wild doves
      from Brazil.
AB  - The prevalence and intensity of blood parasites in three species of wild doves
      were studied in the municipality of Junqueiropolis, in the western region of the
      State of Sao Paulo, Brazil. Three species of doves were surveyed: 331 specimens
      of Zenaida auriculata Des Murs, 1847, 62 specimens of Columbina talpacoti
      Temminck, 1811 and 57 specimens of Scardafella squammata Lesson, 1831.
      Haemoproteus columbae Kruse, 1890 was found in blood from all the doves species.
      The prevalence of this parasite was 100% in Z. auriculata, 51.6% in C. talpacoti
      and 19.3% in S. squammata. Specimens of Z. auriculata had a higher intensity of
      infection than the other doves species.

PMID- 11285494
TI  - Malaria vectors in the municipality of Serra do Navio, State of Amapa, Amazon
      Region, Brazil.
AB  - We conducted a survey to determine the vectors of malaria in six localities of
      Serra do Navio municipality, State of Amapa, from 1990 to 1991. Malaria infection
      rates of 29.3%, 6.2% and 20.4% were detected by human blood smears in Colonia
      Agua Branca, Porto Terezinha and Arrependido, respectively. There was no malaria
      infection detected in Serra do Navio. Fifteen species were identified among 3,053
      anopheline mosquitoes collected by human bait and 64.4% were identified as
      Anopheles albitarsis s.l., 16.7% An. braziliensis, 9.5% An. nuneztovari and 5.8%
      An. triannulatus. An. darlingi, the main vector of malaria in the Amazon region
      of Brazil, was scare. Using enzyme-linked immunosorbent assay (ELISA), a total
      positive rate of 0.8% (23/2876) was found for six species: fifteen An. albitarsis
      s.l., four An. nuneztovari, and one of each: An. braziliensis, An. triannulatus,
      An. oswaldoi and An. rangeli. Nine of 23 positive mosquitoes were infected with
      Plasmodium malariae, eight with P. vivax VK210, three with P. vivax VK247 and
      three with P. falciparum. Since An. albitarsis s.l. was collected feeding on
      humans, was present in the highest density and was positive by ELISA for malaria
      sporozoites, it probably plays an important role in malaria transmission in this
      area.

PMID- 11285495
TI  - Prevalence of antibodies to hepatitis B core antigen in blood donors in the
      middle West region of Brazil.
AB  - The prevalence of antibodies to hepatitis B core antigen in 552 prime blood
      donors was of 9.4%. The majority (71.2%) has antibodies to hepatitis B surface
      antigen. The hepatitis B surface antigen was present in 0.7%, all of them
      antibodies to hepatitis B core antigen positive.

PMID- 11285496
TI  - Genetic variability among populations of Lutzomyia (Psathyromyia) shannoni (Dyar
      1929) (Diptera: Psychodidae: Phlebotominae) in Colombia.
AB  - Polyacrylamide gel electrophoresis was used to elucidate genetic variation at 13
      isozyme loci among forest populations of Lutzomyia shannoni from three widely
      separated locations in Colombia: Palambi (Narino Department), Cimitarra
      (Santander Department) and Chinacota (Norte de Santander Department). These
      samples were compared with a laboratory colony originating from the Magdalena
      Valley in Central Colombia. The mean heterozygosity ranged from 16 to 22%, with
      2.1 to 2.6 alleles detected per locus. Nei's genetic distances among populations
      were low, ranging from 0.011 to 0.049. The estimated number of migrants (Nm=3.8)
      based on Wright's F-Statistic, F ST, indicated low levels of gene flow among Lu.
      shannoni forest populations. This low level of migration indicates that the
      spread of stomatitis virus occurs via infected host, not by infected insect. In
      the colony sample of 79 individuals, the Gpi locus was homozygotic (0.62/0.62) in
      all females and heterozygotic (0.62/0.72) in all males. Although this phenomenon
      is probably a consequence of colonization, it indicates that Gpi is linked to a
      sex determining locus.

PMID- 11285497
TI  - Ootaxonomic investigation of five Lutzomyia species (Diptera, Psychodidae) from
      Venezuela.
AB  - The eggshell fine structure of five sand fly species from Venezuela belonging to
      the genus Lutzomyia (L. migonei, L. ovallesi, L. absonodonta, L. gomezi and L.
      panamensis) was examined by scanning electron microscopy. The chorionic
      sculpturing of L. migonei, L. ovallesi, L. absonodonta and L. gomezi was
      characterized by series of columns arranged in palisade to form sinuous ridges.
      In inter-ridge areas, the basal layer was covered with fibrous material. The
      outer chorion of L. panamensis had a pattern known as "mountain- or volcano
      like". The morphology of the posterior pole and aeropyle had a common structure
      in the five species, with some species-specific characters. The eggshell features
      of the five species are compared with those of other phlebotomine sand flies.

PMID- 11285498
TI  - Ultrastructure and chaetotaxy of sensory receptors in the cercaria of a species
      of Allopodocotyle Pritchard, 1966 (Digenea: Opecoelidae).
AB  - Previous investigations of sensory systems in opecoelid cercariae have focused on
      chaetotaxy and ultrastructure of sensory receptors. They revealed chaetotaxic
      patterns within family, genus, and species as well as different receptors.
      Chaetotaxic and ultrastructural observations have rarely been combined. We
      investigated the ultrastructure of cercarial sensory receptors in conjunction
      with chaetotaxy and neuromorphology in a species of Allopodocotyle. Cercariae
      were treated with acetylthiocholine iodide and silver nitrate, and some were
      processed for light, scanning (SEM), and transmission (TEM) electron microscopy.
      Five nerve regions were distinguished. Chaetotaxy was consistent with that of
      other opecoelids. Five types of receptors were distinguished with SEM. Types
      differed in number of cilium-like structures (one or more), length of cilium-like
      structure (short, moderately long, or long), presence or absence of a tegumentary
      collar, and length of tegumentary collar (low, moderately low, or very high).
      Internal ultrastructure of some types revealed unsheathed cilium-like structures,
      basal body, and thickened nerve collars. Possible subtegumentary and sheathed
      receptors are introduced. Some receptor types were site-specific. For example,
      receptors with multiple cilium-like structures were concentrated on cephalic
      region whereas receptors with short cilium-like structure were widespread
      throughout most regions. Ultrastructure and site-specificity observations suggest
      that most receptors are mechanoreceptors.

PMID- 11285499
TI  - Pseudempleurosoma gibsoni n. sp., a new ancyrocephalid monogenean from
      Paralonchurus brasiliensis (Sciaenidae) from off the southeastern coast of
      Brazil.
AB  - Pseudempleurosoma gibsoni n. sp. (Monogenea: Ancyrocephalidae) is described from
      the oesophagus of Paralonchurus brasiliensis (Steindachner) from off the coast of
      Brazil. The type-species of Pseudempleurosoma Yamaguti, 1965, P. carangis
      Yamaguti, 1965, is redescribed and the diagnosis of the genus is amended.
      Metadiplectanotrema Gerasev et al. 1987 is considered synonym of
      Pseudempleurosoma. This genus now contains four species, including P. carangis,
      P. caranxi Gerasev et al., 1987 n. comb., P. myripristi Gerasev et al., 1987 n.
      comb. and the one new species.

PMID- 11285500
TI  - Protective CD8+ T cell responses against the pre-erythrocytic stages of malaria
      parasites: an overview.
AB  - CD8+ T cells have been implicated as critical effector cells in protection
      against the pre-erythrocytic stage of malaria in mice and humans following
      irradiated sporozoite immunization. Immunization experiments in animal models by
      several investigators have suggested different strategies for vaccination against
      malaria and many of the targets from liver stage malaria antigens have been shown
      to be immunogenic and to protect mice from the sporozoite challenge. Several
      prime/boost protocols with replicating vectors, such as vaccinia/influenza, with
      non-replicating vectors, such as recombinant particles derived from yeast
      transposon (Ty-particles) and modified vaccinia virus Ankara, and DNA,
      significantly enhanced CD8+ T cell immunogenicity and also the protective
      efficacy against the circumsporosoite protein of Plasmodium berghei and P. yeti.
      Based on these experimental results the development of a CD8+ T cell inducing
      vaccine has moved forward from epitope identification to planning stages of
      safety and immunogenicity trials of candidate vaccines.

PMID- 11285501
TI  - Detection of circulant tumor necrosis factor-alpha, soluble tumor necrosis factor
      p75 and interferon-gamma in Brazilian patients with dengue fever and dengue
      hemorrhagic fever.
AB  - Pro-inflammatory cytokines are believed to play an important role in the
      pathogenesis of dengue infection. This study reports cytokine levels in a total
      of 54 patients examined in Recife, State of Pernambuco, Brazil. Five out of eight
      patients who had hemorrhagic manifestations presented tumor necrosis factor-alpha
      (TNF-alpha) levels in sera which were statistically higher than those recorded
      for controls. In contrast, only one out of 16 patients with mild manifestations
      had elevated TNF-alpha levels. The levels of interleukin-6 (IL), IL-1beta tested
      in 24 samples and IL-12 in 30 samples were not significantly increased.
      Interferon-g was present in 10 out of 30 patients with dengue. The data support
      the concept that the increased level of TNF-alpha is related to the severity of
      the disease. Soluble TNF receptor p75 was found in most patients but it is
      unlikely to be related to severity since it was found with an equivalent
      frequency and levels in 15 patients with dengue fever and another 15 with dengue
      hemorrhagic fever.

PMID- 11285502
TI  - Antigen incorporation on Cryptosporidium parvum oocyst walls.
AB  - Cryptosporidium parvum oocysts are the infective stages responsible for
      transmission and survival of the organism in the environment. In the present work
      we show that the oocyst wall, far from being a static structure, is able to
      incorporate antigens by a mechanism involving vesicle fusion with the wall, and
      the incorporation of the antigen to the outer oocyst wall. Using immunoelectron
      microscopy we show that the antigen recognized by a monoclonal antibody used for
      diagnosis of cryptosporidiosis (Merifluor(R), Meridian Diagnostic Inc.) could be
      found associated with vesicles in the space between the sporozoites and the
      oocysts wall, and incorporated to the outer oocyst wall by an unknown mechanism.

PMID- 11285503
TI  - Development of an enzyme-linked immunosorbent assay for detection of IgM
      antibodies to Babesia bigemina in cattle.
AB  - A crude antigenic preparation of Babesia bigemina was used to develop an ELISA
      for the detection of IgM antibodies. Optimal dilutions of the antigen, using
      positive and negative reference sera, were determined by checkerboard titrations.
      Negative sera from cattle imported from tick-free areas, serum samples collected
      from infected B. bigemina cattle were used to validate the test. The specificity
      was 94% and sensitivity of the Elisa 87.5%. Sera from 385 cattle deriving from
      areas free from tick-borne diseases, which were submitted to a preimmunization
      process, were screened by this technique. The Elisa detected seroconversion on
      the 14th day post-inoculation in animals either infested with Boophilus microplus
      ticks (infected with B. bigemina), or inoculated with B. bigemina infected blood.
      Antibody titers decreased after day 33; however, all animals remained positive
      until the end of the experiment (124 days). The ELISA described may prove to be
      an appropriate serological test for the detection of IgM antibodies against B.
      bigemina.

PMID- 11285504
TI  - Enzyme-linked immunosorbent assay for detection and quantification of
      Cryptococcus neoformans antigen.
AB  - An enzyme-linked immunosorbent assay was standardized for the detection of
      cryptococcal antigen in serum and cerebrospinal fluid. The system was evaluated
      in clinical samples from patients infected by human immunodeficiency virus with
      and without previous cryptococcosis diagnosis. The evaluated system is highly
      sensitive and specific, and when it was compared with latex agglutination there
      were not significant differences. A standard curve with purified Cryptococcus
      neoformans antigen was settled down for the antigen quantification in positive
      samples.

PMID- 11285505
TI  - Mutations in the rpoB gene of rifampicin-resistant Mycobacterium tuberculosis
      strains isolated in Brazil and France.
AB  - We evaluated the mutations in a 193bp of the rpoB gene by automated sequencing of
      rifampicin (RMP)-resistant and susceptible Mycobacterium tuberculosis strains
      isolated from Brazil (25 strains) and France (37 strains). In RMP-resistant
      strains, mutations were identified in 100% (16/16) from France and 89% (16/18)
      from Brazil. No mutation was detected in the 28 RMP-susceptible strains. Among
      RMP-resistant or RMP-susceptible strains deletion was observed. A double point
      mutation which had not been reported before was detected in one strain from
      France. Among French resistant strains mutations were found in codons 531
      (31.2%), 526, 513 and 533 (18.7% each). In Brazilian strains the most common
      mutations were in codons 531 (72.2%), 526 (11.1%) and 513 (5.5%). The
      heterogeneity found in French strains may be related to the fact that most of
      those strains were from African or Asian patients.

PMID- 11285506
TI  - Relationship between biological behaviour and randomly amplified polymorphic DNA
      profiles of Trypanosoma cruzi strains.
AB  - Once known some biological characteristics of six Trypanosoma cruzi strains,
      randomly amplified polymorphic DNA (RAPD) analysis was made. Cluster analysis by
      UPGMA (unweighted pair group method analysis) was then applied both to biological
      parameters and RAPD profiles. Inspection of the UPGMA phenograms indicates
      identical clusters, so supporting that usefulness of biological parameters to
      characterization of T. cruzi strains still remains.

PMID- 11285507
TI  - Expression of mosquito active toxin genes by a Colombian native strain of the
      gram-negative bacterium Asticcacaulis excentricus.
AB  - Mosquito control with biological insecticides, such as Bacillus sp. toxins, has
      been used widely in many countries. However, rapid sedimentation away from the
      mosquito larvae feeding zone causes a low residual effect. In order to overcome
      this problem, it has been proposed to clone the Bacillus toxin genes in aquatic
      bacteria which are able to live in the upper part of the water column. Two
      strains of Asticcacaulis excentricus were chosen to introduce the B. sphaericus
      binary toxin gene and B. thuringiensis subsp. medellin cry11Bb gene cloned in
      suitable vectors. In feeding experiments with these aquatic bacteria, it was
      shown that Culex quinquefasciatus, Aedes aegypti, and Anopheles albimanus larvae
      were able to survive on a diet based on this wild bacterium. A. excentricus
      recombinant strains were able to express both genes, but the recombinant strain
      expressing the B. sphaericus binary toxin was toxic to mosquito larvae. Crude
      protease A. excentricus extracts did not degrade the Cry11Bb toxin. The
      flotability studies indicated that the recombinant A. excentricus strains
      remained in the upper part of the water column longer than the wild type Bacillus
      strains.

PMID- 11285509
TI  - A soil emergence trap for collections of phlebotomine sand flies.
AB  - The identification of breeding sites of sand flies is of great epidemiological
      interest. A soil emergence trap for investigating potential sand fly breeding
      sites is described. The trap was tested in two rural areas in the Mogi Guacu
      River Valley where the American cutaneous leishmaniasis is an endemic disease.
      Seventy-three sand fly individuals of three species, Lutzomyia intermedia s. l.,
      L. whitmani and L. pessoai, were collected on the forest floor and peridomicile.

PMID- 11285508
TI  - Morphologic aspects of Tetratrichomonas didelphidis isolated from opossums
      Didelphis marsupialis and Lutreolina crassicaudata.
AB  - Tetratrichomonas didelphidis (Hegner & Ratcliffe, 1927) Andersen & Reilly, 1965
      is a flagellate protozoan found in the intestine, cecum, and colon of Didelphis
      marsupialis. The parasitic protozoa used in this study was found and isolated in
      the intestine of opossums in Pavlova starch-containing medium in Florianopolis,
      State of Santa Catarina, Brazil, from D. marsupialis and Lutreolina
      crassicaudata. The strains were cultivated in Diamond medium without maltose and
      with starch solution, pH 7.5 at 28 degrees C. The specimens were stained by the
      Giemsa method and Heidenhain's iron hematoxylin. The light microscopy study of
      the trophozoites revealed the same morphologic characteristics as specimens
      previously described.

PMID- 11285510
TI  - Survival of tubercle bacilli in heat-fixed and stained sputum smears.
AB  - We used a slide culture technique to detect tubercle bacilli surviving in sputum
      smears (n=46) after conventional heat fixation and Ziehl-Neelsen staining. In all
      heat-fixed sputum smears, tubercle bacilli survived after time 0 (n=22), 24 h
      (n=7), 48 h (n=7), 72 h (n=4), and seven days (n=6). None of the stained sputum
      smears showed growth on slide cultures. Viable tubercle bacilli remaining in heat
      fixed sputum smears for at least seven days may present an infection risk to
      laboratory staff. Thus, sputum smears should be stained immediately by the Ziehl
      Neelsen method or stored in a safe container to avoid transmission of
      tuberculosis.

PMID- 11285511
TI  - [Work conditions and automation: the case of glassblower].
AB  - OBJECTIVE: To investigate how the use of different technologies, organizational
      structures, and task control determine the health-disease process in workers.
      METHODS: The study was developed in two glass industries, one automated and the
      other manual, in the city of S. Paulo, Brazil, between 1996 and 1997. Ergonomics
      methods were used as main principles underlying the techniques of data
      collection. The techniques applied were case study and group comparisons,
      including a direct observation of the work condition, interviews and a
      questionnaire answered by all 41 workers of the workplaces studied: operators of
      automated machines (27 workers) and manual glass blow operators (14 workers). The
      questions were about their jobs and workplace characteristics and health
      complaints. The data were analyzed using Epi Info 6. RESULTS: The comparison
      between the two group of workers showed statistically significant differences in
      relation to workers' perceptions about excessive noise, work tools, posture while
      performing their work and complaints of pain in the arms. There were also
      identified differences in risk factors: movement repetition seen in the manual
      industry and those related to work organization in both industries, such as work
      rhythm, employees' participation in important decisions and training.
      CONCLUSIONS: The use an ergonomics methodology was perfectly adequate. Manual
      industry workers seem to play a role that makes them feel they have an important
      participation in the work process, as they performed a significant part of the
      total work, contrasting with automatic industry workers, which task is only of
      supervising the process, where the machine is the actual producer.

PMID- 11285512
TI  - [Effect of design in cluster sampling to estimate the distribution of occupations
      among workers].
AB  - OBJECTIVE: To describe the effect of design associated with a sample survey
      carried out to estimate the distribution of occupations within an economic active
      population. METHODS: A cluster sample of households, chosen from a comprehensive
      directory via systematic random sampling, was performed including 4,782 of all
      residences in Botucatu, Brazil, between June and July 1997. RESULTS: Of the 4,782
      households, 17,219 subjects were assessed. Due to the loss of distribution
      heterogeneity of the occupations within the households, the effect of design
      found ranged from 1.00 to 1.96. CONCLUSIONS: The results suggest that when
      planning similar studies aiming at estimating the distribution of occupations
      among economic active populations, the effect of design should be estimated as
      e=1.50 for surveys in urban areas, and e=2.00 for surveys in rural areas.

PMID- 11285513
TI  - Housework, paid work and psychiatric symptoms.
AB  - OBJECTIVE: To evaluate the hypothesis that work burden, the simultaneous
      engagement in paid work and unpaid family housework, is a potential risk factor
      for psychiatric symptoms among women. METHODS: A cross-sectional study was
      carried out with 460 women randomly selected from a poor area of the city of
      Salvador, Brazil. Women between 18 to 70 years old, who reported having a paid
      occupation or were involved in unpaid domestic activities for their families,
      were eligible. Work burden-related variables were defined as: a) double work
      shift, i.e., simultaneous engagement in a paid job plus unpaid housework; and b)
      daily working time. Psychiatric symptoms were collected through a validated
      questionnaire, the QMPA. RESULTS: Positive, statistically significant
      associations between high (>7 symptoms) QMPA scores and either double work shift
      (prevalence ratio - PR=2.04, 95% confidence interval - CI: 1.16, 2.29) or more
      than 10 hours of daily work time (PR=2.29, 95% CI: 1.96, 3.43) were found after
      adjustment for age, marital status and number of pre-school children.
      CONCLUSIONS: Major correlates of high QMPA scores are work burden variables.
      Being married or having pre-school children are also associated with high QMPA
      scores only when associated with work burden.

PMID- 11285514
TI  - [Men participation in contraception according to women's perspective].
AB  - OBJECTIVE: To identify women's perceptions on men's participation in
      contraception. METHODS: Home interviews in the southern region of the city of S.
      Paulo, SP, Brazil, were carried out. The participant sample was of 254 female
      users of reversible contraceptive methods, who claimed to have sexual partners at
      moment of the interview. Statistical analysis of the demographic variables and
      content analysis techniques of the open questions were performed. RESULTS: In
      78.8% of the cases, the contraceptive method of choice was of exclusive female
      use (pills, injectable, IUD, diaphragm). In spite of the high prevalence of
      female contraceptive methods, 82.7% of the participants asserted that their male
      partners were active participants in the contraception, which shows a discrepancy
      between the method used and their perception on men's participation. The main
      categories concerning women's perceptions on men's participation in contraception
      were: men support for the women to use female contraceptive methods and the
      occasional use by men of male contraceptive method when a woman needs to
      temporarily interrupt the use of her current contraceptive method. CONCLUSIONS:
      Women perceive men's participation in contraception as a support for them to use
      contraceptive methods that are highly efficient. The partner's support may be
      translated by buying the contraceptive pills, reminding the woman of taking them
      or expressing their opinion about the desired number of children. Women see
      contraception as an activity of her responsibility and their partners have an
      auxiliary role.

PMID- 11285515
TI  - [Oral contraceptive and breast cancer: a case-control study].
AB  - OBJECTIVE: To investigate the association between breast cancer and the duration
      of use of oral contraceptives (OC), and age it started to be used in a population
      of Pelotas, Southern Brazil. METHODS: There were identified 250 incident cases of
      breast cancer in patients aged 20 to 60 years from records of pathology
      laboratories and there were enrolled 1,020 controls drawn from hospital and
      neighbourhood population. For 90 cases identified in Pelotas, 270 hospital
      controls and 270 neighbourhood controls were selected, for another 78 cases in
      Pelotas, 234 controls were selected, and for 82 cases from other municipalities,
      246 hospital controls were selected. Controls were matched by age. Adjusted
      analysis was performed using conditional logistic regression. RESULTS: No
      association between oral contraceptive use and breast cancer was found
      (OR=1.1;CI95% 0.7 - 1.6 for hospital controls, and OR=0.9;CI95% 0.6 - 1.6 for
      neighbourhood controls) neither for different duration of use or starting age. To
      increase the test power, 250 cases and all 1020 controls were analyzed together,
      and an odds ratio of 1.6 (CI95% 1.0 - 2.4) was found for women older than 45
      years of age who had been using oral contraceptives for five years or more.
      CONCLUSIONS: No evidence was found of a general association between oral
      contraceptive use and breast cancer. When analyzing the whole date set, with all
      neighbourhood and hospital controls together, for women older than 45 years of
      age who had been using oral contraceptives for more than 5 years, it was found an
      increased risk almost statistically significant (p=0.05).

PMID- 11285516
TI  - [Validation of predictive equations of basal metabolic rate of women living in
      Southern Brazil].
AB  - OBJECTIVE: To measure the basal metabolic rate of women (aged 20 to 40 years)
      living in Porto Alegre, Brazil, and to compare it with estimated values bored on
      published predictive equations. METHODS: Basal metabolic rate was measured by
      indirect calorimetry under standard conditions in the follicular phase of the
      menstrual cycle of 60 volunteers. RESULTS: Mean measured basal metabolic rate (+/
      standard deviation) was 1,185.3+/- 148.6 kcal/24 hours. Estimated basal
      metabolic rates were significantly greater (7% to 17%) than measured basal
      metabolic rate (p<0.0001). CONCLUSIONS: These results show that predictive
      equations are not suitable to estimate basal metabolic rate in these groups of
      women and that the use of estimated basal metabolic rate will lead to an
      overestimation of energy requirements in women with similar characteristics.

PMID- 11285517
TI  - [Factors associated with abdominal obesity among childbearing-age women].
AB  - OBJECTIVE: To investigate variables potentially associated with abdominal obesity
      among childbearing-age women. METHODS: A total of 781 women were studied based on
      data from the Nutrition and Health Survey conducted in 1996 in the municipality
      of Rio de Janeiro, Brazil. Abdominal obesity was defined as waist girth (WG) > 80
      cm or waist:hips girth ratio (WHR) > 0.85. Statistical analysis involved
      calculation of central trend measures. Calculating the odds ratio using
      multivariate logistic regression tested the association between abdominal obesity
      and BMI, age, parity, and tobacco use. RESULTS: The highest frequencies of
      abdominal obesity were observed in women over 35 years of age and those with two
      or more children (50.7%). OR showed the effect of interaction between parity and
      age for WG>80 cm when only the effect of these two variables was controlled.
      Based on the logistic regression models, the study showed that when the
      population was categorized into women with and without overweight, schooling was
      the only factor associated with WHR, while the association with age and parity
      disappeared for WG>80 cm. CONCLUSIONS: Abdominal obesity in this population group
      is independent of age and parity when adjusted by relative weight, with overall
      adiposity and schooling as the greatest determinant. Having more schooling meant
      having a smaller WHR. It is crucial to implement strategies to prevent the
      development of obesity in childbearing-age women.

PMID- 11285518
TI  - [Analysis of household expenditures with food in the city of S. Paulo in the
      1990's].
AB  - OBJECTIVE: To identify food consumption patterns in the city of S. Paulo, from
      1990 to 1996, and compare these patterns with those derived from nutritionally
      balanced food baskets (FB). METHODS: Household budget surveys were verified and
      the percentage of food expenditures was assessed according to three food groups:
      semi-elaborated, industrialized and non-processed food (an emphasis was given to
      this group). Data on prices to consumer were used to evaluate the relative cost
      of the products and their influence on household budgets. FB were elaborated
      using linear programming. RESULTS: From 1990 to 1996, there was a relative
      increase in household expenditures with industrialized foods and a relative
      decrease with semi-elaborated foods. The percentage of expenditures with non
      processed group revealed an important reduction (35%), but these changes cannot
      be fully explained by variations in products' prices. Results indicated that
      household consumption patterns differ from those recommended in the FB and the
      cost of almost all FB was lower than the actual household expenditures with food.
      CONCLUSIONS: An inadequate nutritional consumption in Sao Paulo's households is
      probable, which carry the risks associated with an insufficient ingestion of
      vegetables and fruits.

PMID- 11285519
TI  - [Minimizing losses and maximizing efficiency in the detection of acute severe
      malnutrition].
AB  - OBJECTIVE: One of the many challenges faced by epidemiologists is to adequately
      plan and optimize subject selection procedures in terms of effectiveness and
      efficiency. In the context of a case-control study involving severe acute
      malnutrition, a two-step subject selection procedure is used. The aim of the
      article is to establish an appropriate cut-off point for the screening phase and
      to achieve a common ground for standards, efficiency in detecting severe
      malnutrition and the two-step procedure. METHODS: The study includes 154 children
      under the age of 2 from two different hospitals. To determine the ideal cut-off
      point of weight-for-age (WFA), the following estimators are of interest: the
      proportion of false negatives (PFN), false positives (PFP) and the percentage of
      total gain by time (ptg). Weight-for-height (WFH) (cut-off point at -2 SDs) is
      used as reference for establishing severe acute malnutrition. RESULTS: The
      magnitude of false negatives declines steadily until the 3rd WFA percentile (P3)
      and reaches zero close to P9. At this point, the PFP is around 0.4. The ptg
      decreases sharply up to P4, declining smoothly towards P10 thereafter (54.5%).
      CONCLUSIONS: The WFA P10 can be recommended for the screening phase. At this cut
      off point, there is still efficiency whereas losses of true cases of severe acute
      malnutrition are minimized.

PMID- 11285520
TI  - [Prevalence and risk factors for anemia among children in Brazil].
AB  - OBJECTIVE: To verify the prevalence of anemia among children aged 0 to 36 months,
      who attend public day care centers in Porto Alegre, Brazil, and assess its
      possible risk factors. METHODS: A cross-sectional study was carried out in 557
      children aged 0 to 36 months of all public day care centers in Porto Alegre.
      Anthropometric measurements and hemoglobin levels were performed. The portable
      HemoCue photometer was employed to measure hemoglobin levels, and anemia was
      considered when the hemoglobin level was below 11 g/dl. Information regarding
      each child was obtained by means of a questionnaire applied to the mother. The
      association of the variables studied to anemia was analyzed using the log
      binomial regression technique applied to the hierarchical model. RESULTS: A 47.8%
      prevalence of anemia was found in this population. The risk factors for anemia in
      the studied group were: families with per capita income equal or less than one
      monthly minimal wage (prevalence ratio - RP =1.6), age between 12 and 23 months
      (RP=1.4), and having 2 or more siblings younger than 5 years old (RP=1.4).
      CONCLUSIONS: There is a high prevalence of anemia among children aged 0 to 36
      months in public day care centers, especially among children with the lowest
      socioeconomic level, in the 12 to 23 months age group, and who have 2 or more
      siblings under 5 years of age, indicating that there is an urgent need for
      effective measures to fight and prevent this condition.

PMID- 11285521
TI  - [The pregnancy during adolescence as a risk factor for low birth weight, Brazil].
AB  - OBJECTIVE: To identify the role of pregnancy during adolescence as a risk factor
      to low birth weight (LBW). METHODS: A stratified sample of live births from the
      Information System of Live Births in the municipality of Rio de Janeiro, in the
      period 1996-98, was selected. The risk factors of LBW were analyzed for the two
      strata composed by the mother age, 15-19 and 20-24 years old. For the statistical
      analysis, odds ratios and correspondent confidence intervals were estimated.
      Logistic regression procedures were used. RESULTS: The LBW was significantly
      greater among the adolescent mothers group than the 20-24 years one. Regarding
      prenatal care, adolescents had a lower number of appointments and a higher
      percentage of no attendance. More than 50% of the older mothers completed high
      school, but only 31.5% among the younger mothers had the same level of
      instruction. The percentage of premature live births in this group was
      significantly greater. Differences were observed by type of hospital (public or
      private) and there was a predominant use of public hospitals by the adolescents.
      The logistic regression analysis showed a significant effect of the mother age on
      LBW, even when controlled for other variables. CONCLUSIONS: The results suggest
      that further investigation on the mechanisms that underlie the association
      between LBW and pregnancy during adolescence should be carried out, taking into
      consideration sociocultural factors such as poverty and social deprivation, as
      well as biological and nutritional factors during pregnancy.

PMID- 11285522
TI  - Age transition of tuberculosis incidence and mortality in Brazil.
AB  - OBJECTIVE: Before the Aids pandemic, demographic transition and control programs
      prompted a shift in the age of incidence of tuberculosis from adults to older
      people in many countries. The objective of the study is to evaluate this
      transition in Brazil. METHODS: Tuberculosis incidence and mortality data from the
      Ministry of Health and population data from the Brazilian Bureau of Statistics
      were used to calculate age-specific incidence and mortality rates and medians.
      RESULTS: Among reported cases, the proportion of older people increased from
      10.5% to 12% and the median age from 38 to 41 years between the period of 1986
      and 1996. The smallest decrease in the incidence rate occurred in the 30 - 49 and
      60+ age groups. The median age of death increased from 53 to 55 years between
      1980 and 1996. The general decline in mortality rates from 1986 to 1991 became
      less evident in the 30+ age group during the period of 1991 to 1996. A direct
      correlation between age and mortality rates was observed. The largest proportion
      of bacteriologically unconfirmed cases occurred in older individuals.
      CONCLUSIONS: The incidence of tuberculosis has begun to shift to the older
      population. This shift results from the decline in the annual risk of infection
      as well as the demographic transition. An increase in reactivation tuberculosis
      in older people is expected, since this population will grow from 5% to 14% of
      the Brazilian population over the next 50 years. A progressive reduction in HIV
      related cases in adults will most likely occur. The difficulty in diagnosing
      tuberculosis in old age leads to increased mortality.

PMID- 11285523
TI  - [Diabetes mellitus at the primary health care level in Southern Brazil:
      structure, course of action and outcome].
AB  - OBJECTIVE: To describe and evaluate the structure, course of action, and the
      outcome of diabetic patient care delivered at primary health care level in
      Pelotas, Southern Brazil. METHODS: Through a cross-sectional study all of 32
      health centers in the region were assessed, along with the 61 doctors who were
      managing diabetic patients. A sample of 378 diabetic patients who attended these
      health centers was also included. Patients were interviewed at home and their
      glucose capillary blood level, blood pressure and body mass index were assessed
      and compared with standard parameters. Course of action and structure components
      were compared against the basic recommendations for the care of diabetic
      patients. RESULTS: Most centers didn't meet the basic recommendations. Blood
      pressure measurement was the most reported action in the physical examination in
      the first visit. As part of the management plan set in the first visit, almost
      85% of the doctors reported to prescribe a special diet and 72% referred
      recommending physical exercise. For laboratory monitoring, all doctors reported
      asking for fasting blood glucose and 60% of them reported checking their
      patients' glycated hemoglobin. The rate of disease control ranged from 6 to 11%,
      according to the Latin American Diabetes Association and the Ministry of Health
      parameters, respectively. CONCLUSIONS: Although currently undersupplied, the
      primary health sector is potentially able to improve in its three components
      (structure, course of actions and outcome) by training medical doctors and their
      compliance with established guidelines.

PMID- 11285524
TI  - Incidence rate and spatio-temporal clustering of type 1 diabetes in Santiago,
      Chile, from 1997 to 1998.
AB  - OBJECTIVE: To estimate the incidence rate of type 1 diabetes in the urban area of
      Santiago, Chile, from March 21, 1997 to March 20, 1998, and to assess the spatio
      temporal clustering of cases during that period. METHODS: All sixty-one incident
      cases were located temporally (day of diagnosis) and spatially (place of
      residence) in the area of study. Knox's method was used to assess spatio-temporal
      clustering of incident cases. RESULTS: The overall incidence rate of type 1
      diabetes was 4.11 cases per 100,000 children aged less than 15 years per year
      (95% confidence interval: 3.06 - 5.14). The incidence rate seems to have
      increased since the last estimate of the incidence calculated for the years 1986 
      1992 in the metropolitan region of Santiago. Different combinations of space
      time intervals have been evaluated to assess spatio-temporal clustering. The
      smallest p-value was found for the combination of critical distances of 750
      meters and 60 days (uncorrected p-value = 0.048). CONCLUSIONS: Although these are
      preliminary results regarding space-time clustering in Santiago, exploratory
      analysis of the data method would suggest a possible aggregation of incident
      cases in space-time coordinates.

PMID- 11285525
TI  - [Zoonotic brucellosis risk associated with clandestine slaughtered porks].
AB  - To determine the sanitary risk to human health, 59 sera samples of clandestine
      slaughtered porks were examined through serologic procedures and have
      demonstrated to have anti-Brucella antibodies and antibodies titles suggestive of
      brucellosis infection. Surveillance measurements are recommended to prevent
      potential risk of zoonotic infection.

PMID- 11285526
TI  - [Multiprofessional healthcare team: concept and typology].
AB  - This paper introduces concept and typology to teamwork as well as criteria to
      identify types of teams. The concept and the typology were developed based on the
      literature and research on multi-professional work in healthcare, based in the
      theory of studies on work process in healthcare and in the theory of
      communicative action. According to this theoretical proposition, teamwork is a
      form of collective work characterized by a reciprocal relationship between
      technical interventions and the interaction of agents. The proposed typology
      refers to two forms of teams: integrated teams as opposed to groups of people.
      The criteria to identify the types of team are related to communication among
      work agents; technical differences and inequality in social recognition of
      specialized works; formulation of a common care program; specificity of each
      professional area; flexibility of work division; and technical autonomy.

PMID- 11285527
TI  - Pancreatic pseudocyst treated by laparoscopic Roux-en-Y cystojejunostomy. Report
      of a case and review of the literature.
AB  - Advances in laparoscopic surgical technique and instrumentation have furthered
      our ability to perform more complex laparoscopic procedures. We report the case
      of a 45-year-old man in whom a giant pancreatic pseudocyst developed after
      biliary pancreatitis. He underwent laparoscopic internal drainage by a Roux-en-Y
      cyst-jejunal anastomosis after unsuccessful percutaneous drainage. The surgical
      technique and a review of the current literature is presented. We conclude that
      although laparoscopic internal drainage technically is feasible in selected
      cases, additional data are required to define the role of this surgical approach
      in the treatment of pancreatic pseudocysts.

PMID- 11285528
TI  - An unusual complication after percutaneous drainage of a pancreatic pseudocyst
      into the stomach.
AB  - In the period between September 1995 and June 1999, we performed percutaneous
      drainage into the stomach in 12 patients. There were no complications or
      pseudocyst recurrences on insertion or after endoscopic removal of the catheter,
      which was left in site for 1 year on average. After endoscopic removal of the
      drainage catheter, one of the patients presented with a cystic formation in the
      stomach wall, which caused stomach emptying disorder. Therefore, the patient had
      to be reoperated. The cyst wall was incised and a part of the cystic wall sampled
      for histological examination. The cyst was then drained into the isolated Roux
      loop of the jejunum. Histological findings of the cystic wall specimen showed the
      presence of granulation tissue and smooth muscle layers with ganglia cells of
      myenteric nerve plexus. Despite this complication, we believe that percutaneous
      endoscopically and ultrasonographically guided drainage of pancreatic pseudocyst
      into the stomach by means of a double pigtail catheter is a good method that
      yields encouraging results in sonographically selected cases. The position of the
      drainage catheter needs to be checked endoscopically, and the catheter should be
      removed only after 1 year.

PMID- 11285529
TI  - The role of laparoscopic biopsies in lumbar spondylodiscitis.
AB  - The infection of an intervertebral disk is a serious condition. The diagnosis
      often is elusive and difficult to make. It is imperative to have appropriate
      microbiologic specimens before the initiation of treatment. We report the case of
      a 51-year-old woman with lumbar spondylodiscitis caused by infection after the
      placement of an epidural catheter for postoperative analgesia. A spinal magnetic
      resonance imaging (MRI) scan confirmed the diagnosis, but computed tomography
      (CT)-guided fine-needle biopsy did not yield adequate material for a
      microbiologic diagnosis. Laparoscopic biopsies of the involved disk provided good
      specimens and a diagnosis of Propionibacterium acnes infection. We believe that
      this minimally invasive procedure should be performed when CT-guided fine-needle
      biopsy fails to yield a microbiologic diagnosis in spondylodiscitis.

PMID- 11285531
TI  - Telesurgical laparoscopic cholecystectomy between two countries.
AB  - Telesurgery is a form of operative videoconferencing in which a remotely located
      surgeon observes a procedure through a camera and provides visual and auditory
      feedback to the operative site. With the use of more robotic devices in
      laparoscopic surgery, various forms of telesurgery have been tried. We describe
      the first two international telesurgical, telementored, robot-assisted
      laparoscopic cholecystectomies performed in the world, between the Johns Hopkins
      Institute, Baltimore, Maryland, USA, and the National University Hospital,
      Singapore.

PMID- 11285530
TI  - Endoscopic surgery for lateral cervical cysts. A report of three cases.
AB  - Recently, endoscopic surgery has been applied to cervical exploration. We have
      developed new techniques for endoscopic neck surgery, and in this paper report
      our experience with three patients with lateral cervical cysts. A 5- or 10-mm
      midline trocar for the endoscope and two 5- or 10-mm lateral trocars were
      inserted from the anterior chest wall and/or both axillary fossae to avoid neck
      scars. There were no intraoperative complications. Slight subcutaneus emphysema
      was present postoperatively, but it was limited to the neck and disappeared in a
      few days. The incisions were completely covered by the patients' undergarments.
      This is the first report of endoscopic lateral cervical cystectomy.

PMID- 11285532
TI  - Surgical clips as a nidus for stone formation in the common bile duct.
AB  - We report the case of a 40-year-old woman who presented with symptomatic
      gallbladder stones. A laparoscopic cholecystectomy was performed using metallic
      clips. Three years later, she underwent a endoscopic retrograde
      cholangiopancreatography (ERCP) for interscapular and right upper quadrant pain,
      jaundice, and fever. This examination revealed a stone and clips in the common
      bile duct (CBD). A sphinteroctomy was undertaken, but the stone could not be
      extracted despite multiple attempts. Ultimately, a Kocher incision was required
      to achieve choledocotomy and extraction of the stone and the clips.

PMID- 11285533
TI  - Laparoscopic repair of a Spigelian hernia using an expanded
      polytetrafluoroethylene (ePTFE) mesh.
AB  - Spigelian hernia are rare and difficult to diagnose. The use of the laparoscope
      has simplified the diagnosis, clarified its localization, and facilitated the
      subsequent repair of these hernias. We describe a Spigelian hernia treated with
      an expanded polytetrafluoroethylene (ePTFE) patch that was applied as an
      peritoneal onlay. We added coagulation of the hernial sac to the standard
      technique in order to prevent formation of a seroma, a frequent complication of
      the use of an ePTFE patch.

PMID- 11285534
TI  - Laparoscopic management of Spigelian hernia.
AB  - Spigelian hernia (SH) is an uncommon abdominal wall hernia. Its clinical symptoms
      are not characteristic, and the preoperative diagnosis is often difficult because
      SH can simulate the symptoms of more classical lower quadrant abdominal diseases.
      We report a case of SH in an 80-year-old woman that was complicated by
      incarceration and diagnosed by physical examination and ultrasound. At the time
      of presentation, she had an abdominal mass that was soft and occasionally
      painful, and aggravated by movements that increase intraabdominal pressure.
      Laparoscopic examination of the abdominal cavity identified the incarcerate
      jejunum ansae. The defect was a large opening in the peritoneum along the lateral
      margin of the rectus abdominis muscle. After dissection of the intestinal
      adhesions, a prosthetic polypropylene mesh was introduced and fixed with staples
      into the lateral abdominal wall. There were no postoperative complications. We
      conclude that the laparoscopic approach is a feasible alternative to the
      conventional open technique that is easy, safe, and allows excellent operative
      visualization.

PMID- 11285535
TI  - Capnocytophaga pleural empyema following laparoscopic Nissen fundoplication. A
      rare complication, a rare pathogen.
AB  - Empyema complicating laparoscopic fundoplication is exceedingly rare, as is
      Capnocytophaga infection in the immunocompetent host, with the exception of
      gingivitis. We report a 29-year-old healthy man who presented with Capnocytophaga
      empyema 10 days after uneventful elective, laparoscopic Nissen fundoplication for
      gastroesophageal reflux disease. The exact mechanism of this complication is not
      known, but hypotheses, including a mini-Boerrhave's syndrome, can be drawn based
      on knowledge of the operation, the involvement of Capnocytophaga sp., and a
      patient history that included severe gingivitis. Because of prompt operative
      evacuation of the empyema and expedient identification of Capnocytophaga in the
      empyema fluid, appropriate antibiotic therapy was initiated. The infection was
      adequately treated, and the patient recovered fully. To the best of our
      knowledge, this is the first report of such a complication.

PMID- 11285536
TI  - Laparoscopic sigmoid colectomy with intracorporeal hand-sewn anastomosis.
AB  - In recent years, laparoscopy has had a significant impact on colorectal surgery.
      However, to date, totally laparoscopic procedures have required the use of
      stapling devices to fashion the anastomosis. Herein we report a case of totally
      laparoscopic sigmoid colectomy with intracorporeal hand-sewn anastomosis for
      diverticulitis. We describe the surgical technique, focusing on the advantages of
      and indications for the laparoscopic hand-sewn anastomosis.

PMID- 11285537
TI  - Postcoital pneumoperitoneum after hysterectomy.
AB  - Usually, pneumoperitoneum is a serious condition suggesting a perforation of the
      abdominal viscus. Nonsurgical pneumoperitoneum accounts for approximately 10% of
      all cases. The authors present a case of postcoital pneumoperitoneum after a
      hysterectomy. A 46-year-old woman presented to the emergency department 4 months
      after an abdominal hysterectomy with complaints of abdominal discomfort and
      radiographic evidence of free air under the diaphragm. The clinical finding did
      not support the radiographic evidence. An unclear peptic ulcer history led us at
      first to mistakenly diagnose a covered perforation of gastroduodenal ulcer.
      Diagnostic perplexity forced us to perform a laparoscopy after 30 h. The
      abdominal cavity was surprisingly normal, and no perforation was found.
      Nonsurgical postcoital pneumoperitoneum is rare. We solved such a case for the
      first time. By means of laparoscopy, we could exclude perforation of the viscus
      and peritonitis, and the operation was carried out in a minimally invasive way.

PMID- 11285538
TI  - Video-assisted thoracic surgery (VATS) in a patient with impaired pulmonary
      function.
AB  - A 72-year-old woman successfully underwent thoracoscopic wedge resection of the
      lung with the assistance of a minithoracotomy. Poor pulmonary function made her a
      high-risk operative candidate. Video-assisted thoracic surgery with the
      assistance of minithoracotomy may be the treatment of choice for high-risk
      patients with a peripheral pulmonary nodule.

PMID- 11285539
TI  - Wolf in sheep's clothing: spilled gallstones can cause severe complications after
      endoscopic surgery.
AB  - Bile concrements may remain intraperitoneally after laparoscopic cholecystectomy.
      Previously, this was considered harmless, a view supported by some experimental
      studies. Recently, however, spilled gallstones have been identified as a source
      of rare but potentially serious complications. We report a case of a retrohepatic
      abscess and dorsal fistulation after laparoscopic cholecystectomy. Healing was
      achieved only by repeated surgery, including abscess drainage, stone removals,
      and fistula excision. Since 1990, 73 cases with gallstone-related complications
      after laparoscopic cholecystectomy have been reported in the literature. Among
      these complications, intra-abdominal abscesses and transabdominal fistulas were
      predominant. The interval between the cholecystectomy and the appearance of
      complications ranged from 4 days to 29 months, with a peak incidence at 4 months.
      Spillage of small bile concrements or fragments is, with the exception of
      multiple irremovable stones, not commonly an indication for conversion to an open
      procedure. However, the patient needs to be warned about the risk of gallstone
      loss and its associated complications at the time when informed consent is
      obtained. Furthermore, if gallstone loss has occurred, the patient should be
      informed, and the occurrence should be documented.

PMID- 11285540
TI  - A new simple laparoscopic-extracorporeal technique for the repair of a Morgagni
      diaphragmatic hernia.
AB  - We used a new technique to treat a right-sided Morgagni hernia in a symptomatic
      adult with a transverse colon that was herniated in the chest. Three trocars were
      required. The herniated viscera were easily reduced in the abdomen, and the
      diaphragmatic border that was mobilized from the liver showed the elliptical
      diaphragmatic defect (9 x 5 cm); however, the hernial sac was not resected. Four
      transversal 1-cm cutaneous incisions were made just below the costal arch. Using
      a Reverdin needle holder, we introduced eight ligatures under laparoscopic
      control through the abdominal wall and through the free diaphragmatic border.
      Each suture was then held by the grasper and freed from the Reverdin. After the
      Reverdin was extracted and reintroduced more caudally, the intraabdominal suture
      was placed into it and finally extracted again. Before knotting, all the sutures
      were pulled together to achieve perfect closure of the defect. A suction drain
      was placed in the hernial sac. The duration of the procedure was 12 min. The
      patient was discharged on the 5th postoperative day. A review of 20 other
      patients treated via a video-assisted approach is also included here. We found
      this original technique to be extremely simple, rapid, and effective. It can also
      be performed by surgeons who are not specially trained in intracorporeal suturing
      and knotting and can probably also be used for the repair of other types of
      diaphragmatic defects. The use of laparoscopy and magnification allows the
      surgeon to achieve a better point of control for simpler solutions.

PMID- 11285541
TI  - Horseshoe kidney injury during laparoscopic inguinal herniorrhaphy.
AB  - A 23-year-old man was admitted to our department following laparoscopic right
      side inguinal herniorrhaphy at a community-based hospital. Gross hematuria led to
      the diagnosis of renal pelvis injury that was first suspected on sonography. A
      computerized tomography (CT) scan revealed perforation of a horseshoe kidney with
      blood clots in the renal pelvis. Retrograde pyelography showed extravasation into
      perirenal tissue. The renal pelvis injury was managed conservatively by drainage
      of the upper urinary tract by transurethral placement of a mono-J stent. Serial
      sonography tests and a repeated retrograde pyelography revealed complete
      resolution of blood clots and perirenal urinoma. The clinical course was
      uneventful, with the double-J stent left in place for 4 weeks. To our knowledge,
      this is the first case report of a renal pelvis perforation in a horseshoe kidney
      during laparoscopic inguinal herniorrhaphy. In the present case, preoperative
      abdominal sonography would have been helpful to demonstrate the anatomical
      aberration. In general, but even more so in the case of anatomic abnormalities,
      the execution of a mini-laparotomy is recommended to allow a safe insertion of
      the optical trocar. This precaution would ensure that such injuries are avoided.

PMID- 11285542
TI  - Laparoscopic gastric resection for bleeding metastatic choriocarcinoma.
AB  - Although intestinal metastases from extraabdominal malignancies are an infrequent
      occurrence, they may cause obstruction, visceral perforation, or gastrointestinal
      bleeding. We report a case of upper gastrointestinal bleeding from a metastasis
      in the body of the stomach in a 69-year-old man with advanced malignant disease
      treated by laparoscopic wedge resection. Laparoscopic exploration was undertaken
      under general anesthesia, confirming the position of the tumor on the greater
      curve of stomach adjacent to the lower pole of the spleen. The greater curve of
      the stomach was mobilized with the harmonic scalpel. The gastroepiploic arcade
      was divided below the tumor, and local resection of the tumor was performed. The
      specimen was removed in a bag. Postoperatively, the patient made an uneventful
      recovery and was discharged on the 3rd postoperative day. Histological
      examination of the specimen indicated choriocarcinoma. We conclude that in
      selected patients with good functional status, resection of bleeding metastatic
      lesions of the gastrointestinal tract is a useful palliative procedure.
      Laparoscopic resection is especially advantageous in patients with a limited
      prognosis because it shortens postoperative stay and enables early resumption of
      daily activities.

PMID- 11285543
TI  - Targeted laparoscopic abdominal adhesiolysis.
AB  - Postoperative abdominal pathogenic bands may produce intermittent subocclusive
      intestinal crises or chronic abdominal pain. Laparotomy has been widely used to
      define the diagnosis and perform adhesiolysis, but recurrences of the bands are
      frequent. Laparoscopy may reduce their incidence; nevertheless, 10-25% of cases
      recur with this procedure as well. Instead of using widespread adhesiolysis to
      treat this condition, a successful outcome may be achieved by removing only the
      pathogenic bands. It is thus essential to identify them. In order to do so, we
      performed a combined laparoscopic-endoscopic procedure. Following an abdominal
      focused radiological and endoscopic workup, two patients with intermittent
      abdominal pain from colonic subocclusion underwent laparoscopic adhesiolysis.
      This procedure was guided by intraoperative colonoscopy. During laparoscopic
      exploration of the abdominal cavity, intraoperative colonoscopy revealed the site
      of the obstacle whichcorresponded precisely to the position of the colonoscopic
      intraluminal. Thus, we identified the location of the transit obstacle and
      selected the bands to be removed. We then performed a targeted adhesiolysis.
      There were no postoperative complications. Symptom-free abdominal function was
      achieved in both cases 3 days after the operation. Both patients are symptom-free
      1 year after treatment. Our preliminary experience indicates that this combined
      procedure, if properly performed (i.e., with a minimal amount of air inflation),
      is helpful in performing correct laparoscopic adhesiolysis.

PMID- 11285544
TI  - An atypical presentation of upper urothelial tumor.
AB  - In some cases of primary transitional cell carcinoma (TCC), there may be some
      uncertainty in clinical decision making. We present a case in which a pT1-N0
      urothelial tumor was found in the renal pelvis after an open nephrectomy for
      urolithiasis. Because incomplete excision of the ureter can lead to recurrence of
      the TCC, we deemed it necessary to remove the residual ureter. Therefore, a
      combined endoscopic-transvescical laparoscopic ureterectomy was performed. The
      transabdominal approach was chosen for the procedure, because the patient had
      already undergone open nephrectomy with retroperitoneal access and was thus
      likely to have adhesions and inflammation in the region. For the endoscopic phase
      of surgery, a technique of ureteral intussusception was combined with
      transurethral resection. The choice of the endoscopic transurethral procedure was
      prompted by the fact that transurethral resection of the ureteral orifice and
      invagination ureterectomy has already been proposed as the first step of
      nephroureterectomy. The combined endoscopic laparoscopic procedure was not
      technically demanding; the ureterectomy took no longer than an open procedure.
      The surgery was uneventful, and the patient resumed normal activities the day
      after surgery. The broader issue of whether this technique should be adopted by
      the urological community at large as a routine practice requires longer follow-up
      outcome data.

PMID- 11285545
TI  - Hand-assisted laparoscopic live donor nephrectomy in a patient with renal artery
      aneurysm.
AB  - Among the transplantation teams there is an increasing interest in laparoscopic
      live donor nephrectomy. For technical reasons, the use of the left kidney is
      recommended. However, considering the shortage of organ donors, it is likely that
      right-side laparoscopic live donor nephrectomy will need to be considered in
      selected donors, even those with vascular anomalies. Here we report the first
      case of right-side live donor laparoscopic nephrectomy in a patient with a renal
      artery aneurysm. Arteriography showed a 3-cm saccular aneurysm of the main right
      renal artery located at the bifurcation of the secondary branches and associated
      with an inferior polar artery coming directly from the aorta. The patient was
      placed in the lumbotomy position. An 8-cm midline incision was made above the
      umbilicus to insert the HandPort system (Smith & Nephew S.A., 72019 Le Mans
      Cedex2, France). Four additional trocars were introduced. Dissection of the renal
      artery was carried out beyond the level of relieving the aneurysm behind the vena
      cava. The main and polar arteries were clipped, and the renal vein was stapled.
      The kidney was removed through the HandPort and perfused cold ex vivo. The warm
      ischemia time for the kidney was 1 min, and the total operative time was 280 min.
      Vascular abnomalies were corrected ex vivo. The postoperative course of the donor
      was uneventful. At 6 months after transplantation, the graft function was normal.
      The hand-assisted approach is of particular value on the right side where the
      dissection must be carried out behind the vena cava. The HandPort may save few
      precious minutes over the sac extraction technique of the standard laparoscopic
      procedure.

PMID- 11285547
TI  - Pathology of low- and intermediate-grade gliomas.
AB  - Under the current World Health Organization (WHO) classification, gliomas can be
      divided into diffuse variants such as astrocytoma, oligodendroglioma, and mixed
      oligo-astrocytoma versus more discrete subtypes such as pilocytic astrocytoma and
      other less common entities. These tumors have been assigned histologic grades
      ranging from I to IV to reflect expected biological behavior. The ever-growing
      body of literature on genetic alterations of glial neoplasms promises to augment
      therapeutic and prognostic information in the future. An important example is the
      1p and 19q deletions in oligodendrogliomas that recently have been associated
      with chemosensitivity and prolonged patient survival. This article reviews the
      pathology of low- and intermediate-grade gliomas, highlighting practical
      diagnostic and prognostic issues.

PMID- 11285548
TI  - Imaging of low- and intermediate-grade gliomas.
AB  - Imaging plays a crucial role in the diagnosis and management of low- and
      intermediate-grade gliomas. In this article, the traditional role of imaging
      studies in glioma patients and the appearance of some of the more common glial
      tumors on conventional computed tomography (CT) and magnetic resonance (MR)
      examinations are reviewed. The impact that MR spectroscopy and MR perfusion
      imaging have made on the evaluation patients after therapy for glial tumors also
      is reviewed.

PMID- 11285549
TI  - Neurosurgical management of low- and intermediate-grade gliomas.
AB  - Surgery remains an effective treatment for most histologic types of low- and
      intermediate-grade gliomas and is an important part of their initial management.
      Controversies nonetheless abound regarding the timing and goals of surgery for
      these gliomas. This article reviews surgical therapy of low- and intermediate
      grade gliomas, paying special attention to new surgical techniques.

PMID- 11285550
TI  - Three-dimensional conformal radiation treatment planning and delivery for low-
      and intermediate-grade gliomas.
AB  - Three-Dimensional conformal radiation treatment (3D-CRT) planning and delivery is
      an external beam radiation therapy modality that has the general goal of
      conforming the shape of a prescribed dose volume to the shape of a 3-dimensional
      target volume, simultaneously limiting dose to critical normal structures. 3
      Dimensional conformal therapy should include at least one volumetric imaging
      study of the patient. This image should be obtained in the treatment position for
      visualizing the target and normal anatomic structures that are potentially within
      the irradiated volume. Most often, computed tomography (CT) and/or magnetic
      resonance imaging (MRI) are used; however, recently, other imaging modalities
      such as functional MRI, MR spectroscopy, and positron emission tomography (PET)
      scans have been used to visualize the clinically relevant volumes. This article
      will address the clinically relevant issues with regard to low- and intermediate
      grade gliomas and the role of 3D-CRT planning. Specific issues that will be
      addressed will include normal tissue tolerance, target definition, treatment
      field design in regard to isodose curves and dose-volume histograms, and
      immobilization.

PMID- 11285551
TI  - Chemotherapy of low-grade gliomas.
AB  - Histologic subtypes of low-grade gliomas include pilocytic astrocytomas (World
      Health Organization [WHO] grade I), diffuse infiltrating astrocytomas,
      oligodendrogliomas, and mixed oligo-astrocytomas (WHO grade II). Although
      extended survival is typical with these tumors, most patients eventually succumb
      to recurrent or progressive disease despite receiving either adjuvant radiation
      therapy or radiation at the time of recurrence. Not surprisingly, chemotherapy
      for low-grade gliomas has primarily been evaluated in the salvage setting of
      postradiotherapy progression in both adults and children. Unfortunately, the
      published body of literature describing chemotherapy for these tumors is small
      and subject to a number of confounding methodologic limitations. Nonetheless,
      some guidelines for the use of chemotherapy in these patients can be inferred
      from the published experience. The data reviewed clearly identifies a potential
      benefit for PCV chemotherapy (procarbazine, CCNU, and vincristine) in at least a
      subset of patients with low-grade oligodendroglial tumors. Nitrosoureas and
      platinum agents appear to have modest efficacy in recurrent oligodendroglial
      tumors and in some patients with newly diagnosed or progressive low-grade
      astrocytomas; however, surgery and radiation remain the primary treatment
      modalities for this group of malignancies. Until new data becomes available,
      chemotherapy still should be used only as a salvage option in previously
      irradiated patients with recurrent or progressive low-grade gliomas.

PMID- 11285552
TI  - Randomized trials of radiation therapy in adult low-grade gliomas.
AB  - There are two central questions in the radiotherapeutic management of the adult
      patient with a supratentorial low-grade (WHO grade II) astrocytoma, oligo
      astrocytoma, or oligodendroglioma. The first question is one of timing. Following
      tissue diagnosis with or without maximum surgical resection, should immediate
      postoperative radiation therapy (RT) be given, or should RT be deferred to the
      time of local recurrence? The second question is one of dose. Assuming RT is
      given, should lower doses (ie, approximately 45-50 Gray (Gy)) or higher doses
      (ie, approximately 60-65 Gy) be administered? One Phase III prospective
      randomized clinical trial addressing the first question and two addressing the
      second question have been performed. Their results suggest that delayed (versus
      immediate) RT and low-dose (versus high-dose) RT are both acceptable treatment
      strategies despite the bias amongst radiation oncologists (primarily based on
      retrospective data) that immediate and high-dose RT would result in better
      outcome. The schema of the ongoing Radiation Therapy Oncology Group study is
      presented.

PMID- 11285553
TI  - Multidisciplinary management of pediatric low-grade gliomas.
AB  - Low-grade gliomas comprise a heterogeneous group of tumors accounting for 30% to
      40% of all primary central nervous system (CNS) neoplasms in the pediatric
      population. Management of these patients has evolved significantly over the past
      2 decades, the present emphasis being on surgery. Adjuvant therapies, such as
      radiation and/or chemotherapy are generally withheld until symptomatic or
      radiographic progression is evident. The goal of surgery is gross total
      resection, while preserving maximal neurologic function. The goal of radiation
      and chemotherapy is to provide symptom and tumor control with minimal acute and
      late toxicities. Chemotherapy has the additional goal of deferring radiation to
      allow maximal development and maturation of the child's CNS. The incorporation of
      these 3 modalities into the overall care of the pediatric low-grade glioma
      patient involves the multidisciplinary input of the neurosurgeon, radiation
      oncologist, and pediatric neuro-oncologist both at time of diagnosis and
      throughout the course of their disease.

PMID- 11285554
TI  - Multidisciplinary management of adult anaplastic astrocytomas.
AB  - The management of patients with anaplastic astrocytoma (AA) requires
      multidisciplinary involvement. In this article, the literature on the treatment
      of patients with AA is reviewed, emphasizing randomized trials and key
      retrospective studies. The role of surgery, radiation therapy, and chemotherapy
      in newly diagnosed patients and those with recurrent disease is described. Basic
      science insights, advances in neuroimaging and neuropathology, and novel
      therapies targeting invasion, angiogenesis, and growth modulation will hopefully
      lead to improved outcome in this subset of patients with malignant glioma.

PMID- 11285555
TI  - Multidisciplinary management of adult anaplastic oligodendrogliomas and
      anaplastic mixed oligo-astrocytomas.
AB  - Once thought to be rare, oligodendroglial tumors might actually represent up to
      25% of primary glial neoplasms. In recent years, the histologic criteria for the
      diagnosis of oligodendroglioma have been broadened to include most small cell,
      monomorphic glial neoplasms. These refinements have led to an increased
      recognition of oligodendroglial neoplasms, but uniform definitions of pure versus
      mixed oligodendroglioma as well as the criteria for high-grade (anaplastic)
      versus low-grade tumors remain elusive. From a prognostic standpoint, the
      presence of an oligodendroglial component in a malignant glioma predicts longer
      survivals times for patients treated with surgery, and radiation therapy with or
      without chemotherapy. High rates of response to PCV (procarbazine, CCNU and
      Vincristine) chemotherapy also have been noted among patients with anaplastic
      oligodendroglial neoplasms. Ongoing prospective trials seek to clarify the role
      of PCV chemotherapy when added to radiation therapy and surgery. In addition, the
      role of molecular markers as diagnostic aides and guides to therapy and prognosis
      are being explored for patients with pure and mixed anaplastic oligodendroglial
      tumors.

PMID- 11285556
TI  - Effects of the incorporation of CHAPS into SDS micelles on neuropeptide-micelle
      binding: separation of the role of electrostatic interactions from hydrophobic
      interactions.
AB  - It is well known that neuropeptides interact with lipid vesicles in a manner
      similar to biological membranes, with electrostatic interactions between the two
      providing a mechanism for concentrating the peptide at the vesicle's surface,
      followed by hydrophobic interactions between the peptide and the core of the
      vesicle that induce and stabilize secondary structure motifs. In an effort to
      understand these interactions to a greater extent, our group has developed a
      series of anionic micelles (SDS) containing various concentrations of the bile
      salt CHAPS, which is used as a model for cholesterol. The incorporation of CHAPS
      into the hydrophobic core of these micelles should alter the degree to which the
      neuropeptide can insert itself, affecting structure. These interactions were
      investigated using two-dimensional NMR, pulse-field gradient (PFG) NMR, and
      molecular modeling experiments. The results of this study clearly indicate that
      electrostatic and hydrophobic interactions between the micelle and neuropeptide
      are completely independent of one another. Increasing the concentration of CHAPS
      to 15 mM in the micelles blocks the insertion of the hydrophobic side chains of
      the neuropeptide into the hydrophobic core of the micelles. The electrostatic
      interactions as determined by diffusion measurements are not affected by the
      presence of increasing CHAPS concentration. Our observations are consistent with
      the predictions of Seelig (A. Seelig and J. Seelig, "Interaction of Drugs and
      Peptides with the Lipid Membrane," in Structure and Function of 7TM Receptors, T.
      W. Schwartz, S. A. Hjorth, and T. S. Kastrup, Eds., Munksgaard: Location, 1996).

PMID- 11285557
TI  - Controlled proteolysis of amelogenins reveals exposure of both carboxy- and amino
      terminal regions.
AB  - The matrix-mediated enamel biomineralization involves secretion of the enamel
      specific amelogenin proteins that through self-assembly into nanosphere
      structures provide the framework within which the initial enamel crystallites are
      formed. During enamel mineralization, amelogenin proteins are processed by tooth
      specific proteinases. The aim of this study was to explore the factors that
      affect the activity of enamel proteases to process amelogenins. Two factors
      including amelogenin self-assembly and enzyme specificity are considered. We
      applied a limited proteolysis approach, combined with mass spectrometry, in order
      to determine the surface accessibility of conserved domains of amelogenin
      assemblies. A series of commercially available proteinases as well as a
      recombinant enamelysin were used, and their proteolytic actions on recombinant
      amelogenin were examined under controlled and limited conditions. The N-terminal
      region of the recombinant mouse amelogenin rM179 was found to be more accessible
      to tryptic digest than the C-terminal region. The endoproteinase Glu-C cleaved
      amelogenin at both the N-terminal (E18/V) and C-terminal (E178/V) sites.
      Chymotrypsin cleaved amelogenin at both the carboxy- (F151/S) and amino-terminal
      (W25/Y) regions. Interestingly, the peptide bond F/S152 was also recognized by
      the action of enamelysin on recombinant mouse amelogenin whereas thermolysin
      cleaved the S152/M153 peptide bond in addition to T63/L64 and I159/L160 and
      M29/I30 bonds. It was then concluded that regions at both the carboxy- and amino
      terminal were exposed on the surface of amelogenin nanospheres when the N
      terminal 17 amino acid residues were proposed to be protected from proteolysis,
      presumably as the result of their involvement in direct protein-protein
      interaction. Cleavage around the FSM locus occurred by recombinant enamelysin
      under limited conditions, in both mouse (F151/S152) and pig amelogenins (S148/M).
      Our in vitro observations on the limited proteolysis of amelogenin by enamelysin
      suggest that enamelysin cleaved amelogenin at the C-terminal region showing a
      preference of the enzyme to cleave the S/M and F/S bonds. The present limited
      proteolysis studies provided insight into the mechanisms of amelogenin
      degradation during amelogenesis.

PMID- 11285558
TI  - Conformational behavior of nucleotide-sugar in solution: molecular dynamics and
      NMR study of solvated uridine diphosphate-glucose in the presence of monovalent
      cations.
AB  - The nucleotide-sugars are metabolites of primary importance in the biosynthesis
      of polysaccharides and glycoconjugates since they serve as sugar donors in the
      reactions of glycosyltransferases, enzymes that displays a high specificity for
      both donors and acceptors. In order to determine the conformational behavior of
      uridinediphosphoglucose in dilute aqueous solution that includes a
      physiologically relevant concentration of salt, parallel NMR and molecular
      modeling investigations have been conducted. Nine molecular dynamics trajectories
      of 3 ns each were calculated in presence of explicit water and monovalent cations
      with the use of the AMBER force field with recently developed energy parameters
      for nucleotide-sugars (P. Petrova, J. Koca, and A. Imberty, Journal of American
      Chemical Society, 1999, vol. 121, pp. 5535-5547). Theoretical nuclear Overhauser
      effect data were calculated from these simulations using a model-free approach
      that takes into account internal motions. Comparison of theoretical and
      experimental data gives excellent agreement for the region surrounding the
      glucose-phosphate linkage including the pyrophosphate linkage itself. Less
      satisfactory agreement is obtained for the ribose ring and the base orientations.
      On the whole, both NMR and molecular dynamics simulations predict the molecule to
      be flexible, and to visit a large number of conformations while maintaining an
      extended overall shape.

PMID- 11285559
TI  - Crystal structure of a depsipeptide, Boc-(Leu-Leu-Lac)3-Leu-Leu-OEt.
AB  - A sequential polydepsipeptide, Boc-(Leu-Leu-Lac)3-Leu-Leu-OEt (1) (Lac = L-lactic
      acid residue) has been synthesized by the segment condensation method. The
      sequential unit of 1, -Leu-Leu-Lac-, is consisted of two amino acid residues and
      one hydroxy acid residue. X-ray diffraction measurement with an imaging plate
      detector and a direct-methods procedure of Shake-and-Bake successfully revealed
      the crystal structure of 1. In the solid state, the 11-mer depsipeptide, 1, have
      clear alpha-helical conformation even with the three ester linkages.

PMID- 11285560
TI  - Molecular dynamics simulation of adrenocorticotropin (1-10) peptide in a solvated
      dodecylphosphocholine micelle.
AB  - Adrenocorticotropin (ACTH) (1-10), an adrenocorticotropin hormone fragment, has
      been studied by molecular dynamics (MD) simulation in an NPT ensemble in an
      explicit dodecylphosphocholine (DPC) micelle. Two starting configurations of the
      peptide/micelle system, corresponding to the insertion and surface-binding modes,
      were used. A common equilibrated configuration, in which the peptide lies
      parallel to the micellar surface, was reached from both simulations. In the
      initial part of the simulations, distance restraints derived from NMR nuclear
      Overhauser enhancements were incorporated before the peptide reached an
      equilibrium configuration with respect to the micelle. Analyses of the
      trajectories from the subsequent free (unrestrained) MD simulation showed that
      ACTH (1-10) does not conform strictly to a helical structure. The loss of the
      helical structure is due to decreased intramolecular hydrogen bonding accompanied
      by an increase of hydrogen bonding between the amide protons of the peptide and
      the micellar head groups. However, the extent of the latter interaction is less
      pronounced than in the negatively charged SDS micelle. The final structure
      enhances the amphipathic nature of the peptide, facilitating better interactions
      at the water-hydrophobic interface. The primary hydrophobic interactions with the
      micelle came from the side chains of Met4, Phe7, and Trp9. All peptide bonds were
      either hydrated or were involved in intramolecular hydrogen bonding. The
      interactions with the DPC micelle, the conformation of the bound peptide, and the
      dynamics of the peptide, as revealed by the time correlation functions of the N-H
      bonds, were compared with those of the ACTH (1-10)/SDS system studied previously
      by MD simulations.

PMID- 11285561
TI  - Distribution of hepatitis C virus infection in liver biopsies from children and
      adults with chronic hepatitis C.
AB  - Chronic hepatitis C in children is characterized by milder forms of liver damage
      than those found in adults. Such a difference has been attributed to a low viral
      load in children that may lead to poor recognition of infected cells by the
      immune system. One approach that could be used to confirm this hypothesis may be
      to examine the number of infected hepatocytes in liver biopsies. Paraffin
      embedded liver biopsies from 21 children and 15 adults with chronic hepatitis C
      virus (HCV) infection (with a similar duration of the infection) were hybridized
      in situ and the percentage of infected hepatocytes was correlated with the
      histological activity index, alanine aminotransferase levels and HCV viraemia
      levels. Histological activity index and HCV viraemia levels were statistically
      higher (P < 0.05 and P < 0.01 respectively) in adults than in children, and the
      percentage of infected hepatocytes was higher in adults (11.0 +/- 19.7%) than in
      children (4.6 +/- 3.6%), although it did not reach statistical significance.
      Also, the percentage of infected hepatocytes correlated with HCV-RNA
      concentration in serum in both children (r = 0.683, P = 0.001) and adults (r =
      0.768, P = 0.001). The results show that liver damage in children with chronic
      hepatitis C is not related to the extent of infection in the liver. This findings
      support the hypothesis of that liver injury in chronic HCV infection is mediated
      by the host immune response.

PMID- 11285562
TI  - Mosquito cells bind and replicate hepatitis C virus.
AB  - Several studies have demonstrated some hepatitis C virus (HCV) replication in
      lymphocyte and hepatocyte cell lines such as in African green monkey Vero cells.
      The aim of the present study was to select other cell lines able to bind and
      replicate HCV. Human hepatoma PLC/PRF/5 cells, human lymphoma Namalwa cells, Vero
      and mosquito AP61 cells were inoculated with HCV-positive plasma, washed six
      times and examined for the presence of the viral genome at different times post
      infection, using an RT-PCR method. Binding of HCV to cells was estimated by HCV
      RNA detection in cells 2 hr after inoculation and in the last wash of these
      cells. Successive virus passages in cells were carried out. All the cells studied
      were able to bind HCV but only AP61 and Vero cells provided evidence of
      replication and production of infectious virus: virus RNA was detected during 28
      days post-infection in four successive virus passages. CD81 molecules, a putative
      HCV receptor, were detected by cytofluorometric analysis. Vero cells express CD81
      molecules whereas these molecules were not detected on AP61 cells. It is
      suggested that other receptors are involved in HCV binding to Vero and AP61
      cells.

PMID- 11285563
TI  - Evaluation of hepatitis C antibody testing in saliva specimens collected by two
      different systems in comparison with HCV antibody and HCV RNA in serum.
AB  - Two different ELISA assays, the Ortho HCV 3.0 ELISA (Ortho Diagnostics Systems)
      and the Mono-Lisa anti-HCV Plus (Sanofi Diagnostics Pasteur) were evaluated for
      the detection of hepatitis C virus (HCV) antibody in saliva samples. Specimens
      were collected from 152 individuals who participated in a longitudinal cohort
      study on HIV infection, and who used illicit drugs. Saliva specimens were
      collected using two different systems: Salivette (Sarstedt) and Omni-Sal (Saliva
      Diagnostic Systems). Saliva specimens were tested following modified protocols by
      both ELISAs, and the results were compared with serum specimens that were tested
      according to the instructions of the manufacturer. Serum samples of 102 (67%)
      participants were positive by both assays, and 50 persons were negative for HCV
      antibody. A total of 99 of the 102 serum specimens were confirmed as positive
      using Ortho Riba HCV 3.0 (Ortho Diagnostics System) and Deciscan HCV (Sanofi
      Diagnostics Pasteur), and 3 yielded discrepant results. As no cut-off level is
      known for testing saliva samples by ELISA, 3 different levels were chosen: mean
      (M) + 1 standard deviation (SD), M + 2 SD, and M + 3 SD of the optical densities
      of saliva tests of the 50 HCV serum antibody negative persons. At a level of M +
      1 SD and M + 2 SD the Salivette/Mono-Lisa combination gave the greatest
      proportion of HCV antibody positive saliva specimens obtained from the 102 HCV
      serum antibody positive participants, 88% and 79%, respectively. Differences
      between the various collection systems and assay combinations were not
      significant statistically. In 76 of the 102 persons with HCV antibodies in serum,
      HCV RNA was detected in serum. Salivary presence of HCV RNA, however, could not
      be demonstrated. The results show that the assays compared are unsuitable for
      diagnostic use, but the sensitivities of the assays are acceptable for use in
      epidemiological studies.

PMID- 11285564
TI  - Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks in Finland.
AB  - Approximately 20 cases of tick-borne encephalitis (TBE) occur annually in
      Finland. The known endemic areas are situated mainly in the archipelago and
      coastal regions of Finland, with highest incidence in Aland islands. Ixodes
      ricinus panels collected in 1996-1997 from two endemic areas were screened for
      the presence of RNA. Two distinct RT-PCR methods were applied, and were shown to
      have an approximate detection limit of 10 focus forming doses (FFD)/100 microl.
      One out of 20 pools (a total of 139 ticks) from Helsinki Isosaari Island and one
      out of 48 pools (a total of 450 ticks) from Aland were positive with both
      methods, whereas the remaining pools were negative. The observed overall
      frequency (0.34%) in ticks in endemic areas of Finland, was similar to the low
      incidence found by virus isolation in mice in the 1960s (0.5%). Viral RNA was
      detectable in a diluted sample representing 0.005% of a positive pool of ten
      nymphs suggesting that the viral RNA load within an infected tick pool was
      approximately equivalent to 20,000-200,000 FFD. Sequence analysis did not show
      geographical clustering of the Finnish strains, suggesting an independent
      emergence of different TBE foci from the south. TBE virus RNA positive ticks were
      not found in I. ricinus panels consisting of 130 pools (726 ticks) from Helsinki
      city parks or 41 pools (197 ticks) from Vormsi Island in Estonia.

PMID- 11285565
TI  - Association of tumour necrosis factor alpha and interleukin 6 levels with
      cytomegalovirus DNA detection and disease after renal transplantation.
AB  - Cytokines such as tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL
      6) are thought to be important in the pathogenesis of post-transplant
      cytomegalovirus (CMV) disease. CMV infection increases the production of TNF
      alpha and IL-6. Conversely, TNF-alpha switches on the replication of CMV. To
      study the association of these two cytokines with CMV activity and disease, TNF
      alpha and IL-6 levels were assayed in plasma samples taken serially from three
      groups of renal transplant recipients. Group A (n = 12) had CMV disease and
      syndrome; Group B (n = 11) had detectable CMV DNA in plasma or peripheral blood
      leucocytes without disease, i.e., presumed asymptomatic CMV infection, and Group
      C (n = 11) had no detectable CMV DNA nor disease. The median peak TNF-alpha
      levels in patients with CMV disease (Group A) were significantly higher than that
      in Group B or Group C (P < 0.02) whereas the median peak IL-6 levels in group C
      patients were significantly lower than that in group A (P < 0.04) or group B (P <
      0.03). A TNF-alpha level of above 100 pg/ml was significantly associated with CMV
      disease and high plasma CMV load (> 10,000 copies/ml). IL-6 levels above 15 pg/ml
      were significantly associated with CMV DNA detection, but not with CMV disease or
      elevated CMV load. High levels of TNF-alpha or IL-6 were not associated with CMV
      donor/recipient serostatus, HHV-6 or HHV-7 DNA detection, immunosuppressive
      regimen or rejection episodes. The role of TNF-alpha in the pathogenesis of CMV
      disease deserves further investigation.

PMID- 11285566
TI  - Longitudinal analysis of human cytomegalovirus glycoprotein B (gB)-specific and
      neutralizing antibodies in AIDS patients either with or without cytomegalovirus
      end-organ disease.
AB  - Serum neutralizing and glycoprotein B (gB)-specific antibody levels were
      monitored prospectively in AIDS patients who either did or did not develop human
      cytomegalovirus (HCMV) end-organ disease, to delineate further the role of
      antibodies in protecting against HCMV disease. Antibody levels declined
      substantially (at least 4-fold) only in patients who developed HCMV disease; this
      decline in turn occurred concurrently with antigenemia. Nevertheless, AIDS
      patients who remained free of HCMV disease and did not become antigenemic during
      the follow-up period maintained stable levels of serum antibodies, with only
      minor fluctuations. The impact of HAART on the levels of functional anti-HCMV
      antibodies was investigated in a number of AIDS patients. Serum levels and
      kinetics of gB and neutralizing antibodies did not differ significantly between
      patients who responded biologically and virologically to therapy and those who
      failed to respond. In addition, CD4 + cell counts and HIV viral RNA levels did
      not correlate with anti-HCMV antibody titers.

PMID- 11285567
TI  - Prevalence and distribution of human herpesvirus 6 variants A and B in adult
      human brain.
AB  - The presence of human herpesvirus 6 (HHV-6) in brain tissues of 40 consecutive
      post-mortem cases was examined. For each case, autopsy samples were collected
      from the cerebellum, frontal, temporal, parietal and occipital lobes of both
      sides of the brain. HHV-6 DNA was detected by nested polymerase chain reaction
      and characterised into variants A and B. Overall, 97/400 (24.3%) samples were
      positive for HHV-6 DNA with 16 being variant A and 81 being variant B, but none
      of the samples harboured both variants. When analysed by patient, 34/40 (85%) had
      HHV-6 DNA detected in the brain. The viral DNA positivity did not show
      significant variation with gender and age. Four patients harboured variant A, 23
      harboured variant B, and seven had both variants at different positions. The
      results indicate that both HHV-6A and HHV-6B are neurotropic and human brain may
      be another site for latency. HHV-6B was detected in brain tissues of a majority
      (75%) of the studied population and with a widespread distribution within the
      brain. Although the observed prevalence of HHV-6A in brain is lower (27.5%), in
      view of its lower seroprevalence, the neuroinvasive potential of variant A may be
      comparable to that of variant B. Although both variants are potential pathogens
      for the nervous system, the fact that they can exist, probably for most of the
      time, as commensals in human brain needs to be considered when interpreting their
      roles in neuropathology.

PMID- 11285568
TI  - Anorectal melanomas do not harbour the Kaposi sarcoma-associated human
      herpesvirus type 8 DNA.
AB  - Anorectal melanomas are similar to cutaneous melanomas with regard to the mode of
      spread and to the immunophenotype. When compared with patients with cutaneous
      melanoma, those suffering from anorectal melanoma have a much worse outcome. The
      etiology of anorectal melanomas is as yet completely unknown. For anatomical
      reasons, ultra-violet (UV-B) radiation can not cause anorectal melanomas as in
      cutaneous tumours, that are associated with exposure of the skin to UV-B
      radiation. As the cytokine interleukin-6 (IL-6) is known to stimulate melanoma
      tumour cell proliferation and a functional homologue of human IL-6 has been
      identified recently in the HHV-8 genome, this tumorigenic virus might be involved
      in the pathogenesis of anorectal melanomas. Twelve formalin fixed and paraffin
      embedded primary anorectal melanomas from seven female and five male patients
      with a mean age at diagnosis of 71 years (range 38-88 years) were investigated
      for the presence of HHV-8 DNA. Using a specific and highly sensitive polymerase
      chain reaction protocol, this tumorigenic gamma-herpesvirus was not detectable in
      any tumour. This data indicates that HHV-8 is not involved in the development of
      anorectal melanomas.

PMID- 11285569
TI  - Use of bacterially expressed EBNA-1 protein cloned from a nasopharyngeal
      carcinoma (NPC) biopsy as a screening test for NPC patients.
AB  - EBV serological tests have been used for many years as accessory diagnostic
      predictors of nasopharyngeal carcinoma (NPC). To increase the sensitivity and
      specificity of the NPC detection rate, a novel enzyme-linked immunosorbent assay
      (ELISA) was established using a bacterially-expressed GST-EBNA-1 protein,
      containing the EBNA-1 sequence cloned from an NPC patient. Serum samples were
      collected from age- and gender-matched patients with NPC, community control
      subjects and hospital control patients and tested using this ELISA. The
      positivity rates were 78.7% (247/314) in NPC, 11.5% (28/244) in hospital controls
      and 3.8% (10/263) in the community control group. These serum samples were also
      tested for IgA anti-VCA antibodies and their ability to neutralize EBV DNase and
      the sensitivities of the anti-VCA antibody and DNase-neutralization tests also
      were analyzed. The optimum combination is VCA plus EBNA-1, which can identify
      92.5% (287/310) of NPC patients, and shows a specificity of 92.7% (242/261) for
      normal individuals.

PMID- 11285570
TI  - Molecular epidemiology of 'Norwalk-like viruses' associated with gastroenteritis
      outbreaks in New Zealand.
AB  - Outbreaks of gastroenteritis are a major public health problem in New Zealand.
      The introduction of molecular detection methods has now shown that the 'Norwalk
      like viruses' (NLVs) are the major cause of food and waterborne nonbacterial
      gastroenteritis. Reverse transcription and polymerase chain reaction (RT-PCR)
      were used to determine the presence of NLVs in faecal specimens from 83
      nonbacterial gastroenteritis outbreaks occurring in New Zealand between August
      1995 and July 1999. Further characterisation of the NLVs for epidemiological
      purposes was carried out by dot blot DNA hybridisation and DNA sequencing of
      representative outbreak strains. The majority of NLV strains occurring in New
      Zealand since August 1995 are similar to those occurring overseas. The
      predominant New Zealand strain is genetically similar to the Bristol/Lordsdale
      virus group. Several New Zealand outbreaks were attributed to Auckland virus, a
      Mexico-like NLV strain identified as the most likely cause of gastroenteritis
      after consumption of contaminated oysters in 1994. A new strain, designated
      Napier virus, has been identified in six outbreaks since 1996. A number of
      strains closely resembling internationally recognised strains, including
      Southampton virus, Saratoga virus; Desert Shield virus and Melksham virus have
      been associated with gastroenteritis outbreaks across New Zealand. Application of
      these typing methods has provided information on disease transmission for
      epidemiological investigations of public health significance.

PMID- 11285571
TI  - Differential IgM response to conformational and linear epitopes of parvovirus B19
      VP1 and VP2 structural proteins.
AB  - The IgM immune response against conformational and linear epitopes of B19
      structural proteins VP1 and VP2 was examined in serum samples with a suspect B19
      infection to determine the most suitable antigen for use in IgM detection and
      also to evaluate a possible relationship between the course of B19 infection and
      the presence of epitope type-specific IgM. The detection of IgM against
      conformational epitopes was performed by ELISA using undenatured VP1 and VP2
      antigens whereas the detection of IgM against linear epitopes was performed by
      Western blot assays using denatured VP1 and VP2. IgM immune response against VP1
      conformational epitopes appeared dominant, being detected in all serum samples
      positive for specific IgM, whereas IgM against VP2 linear antigen were found less
      frequently, being identified in less than half of the B19 IgM positive sera. In
      the examination of the course of infection, IgM against VP1 conformational
      epitopes appeared in the active phase of B19 infection at the same time and with
      the same frequency as IgM anti VP2 conformational epitopes and anti linear VP1
      epitopes. IgM against VP1 conformational epitopes were seen to be long-lasting
      because in the recent phase of infection they were still present when other
      specific IgM were absent. During the active phase of B19 infection, IgM against
      VP2 linear epitopes were less frequently found than other specific IgM and in the
      recent phase they underwent a rapid temporal diminution. The data demonstrate
      that a sensitive B19 IgM test needs to be performed in diagnostic laboratories by
      ELISA using conformational B19 antigens; Western blot assays can be used only as
      confirmatory tests using VP1 linear antigens.

PMID- 11285572
TI  - Histopathologic impact of TT virus infection on the liver of type C chronic
      hepatitis and liver cirrhosis in Japan.
AB  - The present investigation compared the histological findings in the liver of
      chronic hepatitis C patients who were or were not co-infected with TT virus (TTV)
      to determine the histological and clinical characteristics of TTV infection. One
      hundred eighty patients with chronic hepatitis or liver cirrhosis type C were
      included in this study. Serum samples were tested for the presence of TTV DNA by
      a nested polymerase chain reaction. The liver biopsy specimen of each patient was
      examined, and scores were assigned to indicate the severity of each of the
      following features: inflammatory cell infiltration in the periportal,
      parenchymal, and portal areas; fibrous stage; lymphoid reaction in the portal
      area; portal sclerotic change; perivenular fibrosis; pericellular fibrosis;
      damage of bile duct; and irregular regeneration of hepatocytes. Sixty-four
      (34.4%) of the 180 patients were positive for TTV DNA. The histological features
      of the liver and the blood biochemical parameters of the TTV DNA-positive and TTV
      DNA-negative patients, did not differ significantly except for the score of
      irregular regeneration (IR) of hepatocytes. Among those in the F4 stage of
      fibrosis, the score of IR of the TTV DNA-positive patients was significantly
      higher than that of the TTV DNA-negative patients. In conclusion, chronic TTV
      infection does not modify the biochemical features of chronic hepatitis type C
      patients. TTV may be a risk factor, however, for the development of
      hepatocellular carcinoma in patients with type C liver disease in the F4 stage.

PMID- 11285573
TI  - A regulatory region rearranged BK virus is associated with tubulointerstitial
      nephritis in a rejected renal allograft.
AB  - A renal allograft transplant patient with high serum creatinine presented
      clinical symptoms of rejection. Sections of renal biopsy tissue showed
      mononuclear leukocyte infiltration in the tubulointerstitium and nuclear
      enlargement with inclusions in the tubular epithelium. The morphological
      characteristics resembled polyomavirus-induced interstitial nephritis. Electron
      microscopy of the nuclear inclusions showed paracrystalline arrays of naked viral
      particles with a diameter of 45 nm. Molecular studies revealed that a new variant
      of BK virus (BKV) with rearrangement at the regulatory region was involved in the
      nephritis. The BKV regulatory region contained a tandem repeat from the P-block
      to the Q-block causing duplication of several important transcriptional elements
      or transcriptional factor binding motifs. This is the first report to show a
      naturally occurring BKV variant with regulatory region rearrangement associated
      with tubulointerstitial nephritis.

PMID- 11285574
TI  - Body image in boys: a review of the literature.
AB  - OBJECTIVE: Both scientific research and popular attention have begun to focus on
      the neglected issue of body image in boys. We reviewed the findings of this
      emerging literature. METHOD: Using computer and manual search techniques, we
      located 17 studies that assessed body image attitudes in boys under age 18.
      RESULTS: We located 17 studies, most performed within the last 10 years. Eight
      studies used exclusively questionnaires or interviews; the rest also used figure
      drawings from which the subjects could choose specific images in answer to
      questions. Although boys generally displayed less overall body concern than
      girls, many boys of all ages reported dissatisfaction with their bodies, often
      associated with reduced self-esteem. Whereas girls typically wanted to be
      thinner, boys frequently wanted to be bigger. However, most studies failed to
      distinguish between "bigness" due to increased muscle and that due to fat.
      CONCLUSIONS: Body image dissatisfaction in boys is common and often associated
      with distress. To better assess this phenomenon, future studies should take care
      to separate the indices of muscle and fat.

PMID- 11285575
TI  - Child sexual abuse and later disordered eating: a New Zealand epidemiological
      study.
AB  - OBJECTIVE: This community-based study examined how some women who have
      experienced childhood sexual abuse (CSA) develop an eating disorder (ED), whereas
      others develop depression and anxiety, and others show no adverse psychological
      sequelae. METHODS: A two-stage random community sampling strategy was used to
      select two groups of women: (1) women with CSA prior to age 16 years and (2) a
      comparison group of women reporting no abuse. Both groups completed the Parental
      Bonding Instrument (PBI), the Present State Examination, and additional ICD-10
      eating disorders questions. Information on the nature and frequency of the CSA
      was obtained at interview. CSA women with ED (CSA+ED) were compared with CSA
      women without ED (CSA-noED) and with CSA women with anxiety and/or depression
      (psychiatric comparison group). RESULTS: Higher rates of EDs in women who have
      experienced CSA were confirmed in this study. Belonging to a younger age cohort,
      experiencing menarche at an early age, and high paternal overcontrol on the PBI
      independently increased the risk of developing an ED in women who had experienced
      CSA. Low maternal care was specifically associated with the development of
      anorexia nervosa, whereas early age of menarche differentiated women with bulimia
      nervosa. Younger age and early age of menarche also differentiated the CSA+ED
      women from the psychiatric comparison group. DISCUSSION: Early maturation and
      paternal overcontrol emerged as risk factors for ED development in women with
      CSA. Although these variables are also risk factors in the general population,
      women with CSA may be vulnerable to ED development because these risk factors are
      particular domains of concern that emanate from experiences of CSA.

PMID- 11285576
TI  - Pretreatment motivational enhancement therapy for eating disorders: a pilot
      study.
AB  - Eating disorder patients are notoriously ambivalent about treatment and often
      lack motivation to change. These characteristics may decrease the number of
      patients entering treatment and increase the number of patients dropping out of
      treatment prematurely. OBJECTIVE: The aim of this pilot study was to develop and
      evaluate a motivational enhancement therapy (MET) group program for eating
      disorder patients. The goal of the MET intervention was to increase participants'
      motivation to change, which might be expected to increase the success of future
      treatment of patients with eating disorders. METHOD: Nineteen individuals who
      were referred for specialized treatment took part in the study. The intervention
      was based on existing literature in the field of addictions and modified for
      eating disorders. RESULTS: The motivational measures suggested that the
      participants' motivation to change increased following the intervention. A
      decrease in depressive symptoms and an increase in self-esteem were also found.
      DISCUSSION: The results of this study suggest that MET could be valuable for the
      treatment of eating disorder patients and provide a rationale to conduct further
      research in this area.

PMID- 11285577
TI  - Reducing risk factors for eating disorders: targeting at-risk women with a
      computerized psychoeducational program.
AB  - OBJECTIVE: This controlled study evaluated whether an 8-week program offered over
      the Internet would significantly decrease body image dissatisfaction, disordered
      eating patterns, and preoccupation with shape/weight among women at high risk for
      developing an eating disorder. METHOD: Fifty-six college women were recruited on
      the basis of elevated scores (> or =110) on the Body Shape Questionnaire (BSQ).
      Psychological functioning, as measured by the Eating Disorder Inventory Drive for
      Thinness (EDI-DT) subscale, Eating Disorder Examination-Questionnaire (EDE-Q),
      and the BSQ, was assessed at baseline, posttreatment, and at 10-week follow-up.
      RESULTS: All participants improved over time on most measures, although effect
      sizes suggest that the program did impact the intervention group. DISCUSSION:
      Findings suggest that technological interventions may be helpful for reducing
      disordered eating patterns and cognitions among high-risk women. Future research
      is needed to assess whether such programs are effective over time for prevention
      of and reduction in eating disorder symptomatology.

PMID- 11285579
TI  - Deficits in haptic perception and right parietal theta power changes in patients
      with anorexia nervosa before and after weight gain.
AB  - OBJECTIVE: Our goal was to investigate whether patients with anorexia nervosa
      (AN) show deficits in haptic exploration tasks before and after weight gain.
      METHOD: The haptic exploration tasks consisted of palpating the structure of six
      sunken reliefs in sequence with both hands, eyes closed. After each exploration,
      the structure was reproduced on a piece of paper. A 19-channel digital
      electroencephalogram (EEG; linked ears) was continuously recorded during rest and
      haptic tasks for 10 AN patients (females, mean age: 15.90) and 10 healthy
      controls (CO; females, mean age: 16.14). Mean spectral power density was
      calculated as the mean amplitude of the spectral lines of the theta band (4-8
      Hz). The AN patients were examined again after weight gain (T(0) and T(1)).
      RESULTS: The reproductions submitted by the AN patients were of notably poorer
      quality than those of the CO. Reproduction quality was unchanged after weight
      gain and independent of body mass index and intelligence. Mean exploration time
      was similiar in AN patients and CO. The analysis of spectral EEG power of both
      groups showed significant decrease in power data in the theta frequency band
      during haptic exploration compared with the rest intervals. The comparison of the
      theta power between CO and AN patients during haptic exploration showed major
      differences between the groups in both T(0) and T(1). Theta power was lower in AN
      patients than in the CO over the right hemisphere and right parietal regions.
      DISCUSSION: The quality of reproduction of the haptic stimuli and the theta-power
      changes indicate a cortical dysfunction and deficits in somatosensory integration
      processing of the right parietal cortex in AN patients even after weight gain.

PMID- 11285578
TI  - Hemispheric differences in body image in anorexia nervosa.
AB  - OBJECTIVE: This study tested the hypothesis that women with anorexia nervosa (AN)
      have an inappropriately fatter body image in the left cerebral hemisphere (LH)
      than in the right cerebral hemisphere (RH). METHOD: Women with AN symptomatology
      were compared with thin controls in a divided visual field experiment. Distorted
      and undistorted pictures of their own and someone else's body were flashed
      briefly in the left and right visual fields. Participants judged the pictures as
      thinner than, equal to, or fatter than the actual body size. RESULTS: The AN
      participants judged a higher proportion of fatter distortions as equal to their
      own size. They responded faster when stimuli were presented initially to the LH
      than when they were presented initially to the RH. In contrast, fewer thinner
      distortions were judged as equal to their own body size, and were judged more
      slowly, on LH trials than on RH trials. Controls did not show hemispheric
      differences when judging their own body and AN participants did not show
      hemispheric differences when judging pictures of somebody else. Additional
      analyses revealed that these findings were carried entirely by a subgroup who had
      AN in the past, not by the subgroup who currently had AN. DISCUSSION: The brain
      lateralization paradigm may prove useful in understanding body image disturbance
      in AN patients.

PMID- 11285580
TI  - The positive influence of maternal identification on body image, eating
      attitudes, and self-esteem of Hispanic and Anglo girls.
AB  - OBJECTIVE: The role of maternal identification in the development of girls' body
      image, eating attitudes, and self-esteem was examined. METHOD: Hispanic and Anglo
      girls (n = 410) ages 8-13 were surveyed using the Body Esteem Scale (BES), the
      Children's Eating Attitudes Test, the Piers-Harris Children's Self-Concept Scale,
      and the Child Figure Drawing task. From this sample, normal-weight girls with
      high or low scores on the BES were selected for the main study. Ninety-two mother
      daughter pairs participated in this second phase in which mothers completed
      similar questionnaires and girls performed a Q-sort task measuring maternal
      identification. RESULTS: Maternal identification was positively correlated with
      girls' self-esteem and negatively correlated with eating problems and body
      dissatisfaction. Also, mothers with high self-esteem tended to have daughters
      with high self-esteem. The mothers of girls with low BES scores found a
      significantly greater discrepancy than the mothers of girls with high BES scores
      when contrasting their daughters' current shape with either the ideal figure for
      their daughter or the figure they believed boys would find attractive.
      DISCUSSION: Girls who aspired to be like their mothers in terms of personality
      traits felt better about themselves and their bodies compared with girls with low
      maternal identification.

PMID- 11285581
TI  - Nasogastric feeding in children and adolescents with eating disorders: toward
      good practice.
AB  - OBJECTIVE: This study aimed to provide an insight into the subjective experiences
      of nasogastric feeding from the perspective of patients with eating disorders and
      their parents. METHOD: A semistructured self-report questionnaire was completed
      by patients from two specialist eating disorders units who had received
      nasogastric feeding. Parents' views were also assessed via a similar self-report
      questionnaire. RESULTS: Diverse views were expressed by both patients and
      parents. Some regarded the experience of nasogastric feeding as wholly negative,
      but acknowledged the lack of suitable alternatives. Others had a more positive
      view and identified several helpful aspects. CONCLUSION: Reactions were generally
      more positive than had been anticipated. A number of useful suggestions were made
      regarding how to improve the procedure. These have informed the development of
      guidelines for good practice.

PMID- 11285582
TI  - The role of daily hassles in binge eating.
AB  - OBJECTIVE: The present study investigated the relationship between daily hassles
      and the frequency and caloric intake of eating episodes among normal-weight women
      who engage in binging (n = 17) and those who do not (n = 17). METHOD: For 2
      weeks, participants self-monitored their food intake during the day and completed
      The Hassles Scale each evening before retiring. RESULTS: Results indicated that
      women who engage in binge eating rated daily hassles as significantly more
      stressful than women who do not binge. Also, women who engage in binge eating
      consumed significantly more calories on those days characterized by higher as
      opposed to lower levels of stress. DISCUSSION: Theoretical and clinical
      implications of these findings are discussed.

PMID- 11285583
TI  - Alcohol abuse and dysfunctional eating in adolescent girls: the influence of
      individual differences in sensitivity to reward and punishment.
AB  - OBJECTIVE: An unusually high comorbidity of eating disorders and alcohol abuse
      has been found in clinical and community samples of young women. This paper
      proposes that individual differences in sensitivity to reward and punishment may
      influence the propensity of young women to engage in dysfunctional eating and
      drinking behaviour. METHOD: The Drive for Thinness scale, the Alcohol Use
      Disorders Identification Test and the BIS/BAS scales were administered to 232
      high school girls. RESULTS: Heightened sensitivity to reward was the better
      predictor of alcohol misuse while heightened sensitivity to both reward and
      punishment was predictive of dysfunctional eating. When categorised by group,
      alcohol abusing, dysfunctional eating, and comorbid girls reported greater
      sensitivity to reward than non-disordered girls. Girls with dysfunctional eating
      with and without comorbid alcohol abuse reported greater sensitivity to
      punishment than alcohol abusing only girls. DISCUSSION: These findings suggest
      that girls who abuse alcohol and have dysfunctional eating may share a
      vulnerability to heightened sensitivity to reward, yet be differentiated by
      sensitivity to punishment.

PMID- 11285585
TI  - Total energy expenditure as measured by doubly-labeled water in outpatients with
      bulimia nervosa.
AB  - OBJECTIVE: This study measured total energy expenditure (TEE) in symptomatic
      outpatient women with bulimia nervosa and normal controls. The study aimed to
      test the conceptual model of bulimia nervosa as an illness characterized by a
      physiological state of starvation, despite normal weight. METHOD: Total fat and
      fat-free mass were measured using hydrodensitometry and total energy expenditure
      was assessed via the doubly-labeled water method, in nine normal weight
      outpatient females with DSM-III-R bulimia nervosa and ten healthy female
      controls. RESULTS: Patients and controls were similar in age, body mass index,
      weight, lean body mass, and levels of exercise and general activity. Patients had
      an average baseline binge frequency of 14.7 episodes per week and purge frequency
      of 16.8 times per week, and had been ill for an average of 11.9 years. Group mean
      TEE did not differ between patients and controls (patients 2380 +/- 482 kcal/day,
      controls 2368 +/- 515 kcal day). Observed TEE in the bulimic subjects did not
      differ significantly from TEE predicted on the basis of data from the controls.
      DISCUSSION: This finding of normal TEE in symptomatic outpatients with bulimia
      nervosa is consistent with a previous study that found no difference in TEE in a
      sample of symptomatic inpatients with bulimia nervosa. These data suggest that
      the energy conserving metabolic adaptations characteristic of semi-starvation do
      not occur in patients with bulimia nervosa.

PMID- 11285584
TI  - Antibodies against human putamen in adolescents with anorexia nervosa.
AB  - OBJECTIVE: To examine whether antiputamen antibodies are present in adolescents
      with anorexia nervosa (AN). METHOD: Using enzyme-linked immunosorbent assay
      (ELISA) with an extract of human putamen as an antigen, sera samples obtained
      from 22 adolescents with active AN and from 22 healthy adolescents (control
      group) were assayed for antibodies to neuronal components RESULTS: Mean optical
      density (OD) readings for serum antibodies against human putamen in adolescents
      with AN was significantly greater than the mean OD readings in the control group
      (0.492 +/- 0.086 vs. 0.275 +/- 0.028, p =.02). When serum positivity was defined
      as an OD level greater than 2 SD above the mean control group value (0.541),
      antiputamen antibodies were detected in the blood of 6 AN patients (27%) whereas
      they were detected in the blood of 1 patient (5%) in the control group (p <.05;
      Fisher's exact test). DISCUSSION: The detection of antiputamen antibodies in
      adolescents with AN suggests an underlying immune process at the putamen level in
      some patients with this eating disorder.

PMID- 11285586
TI  - Prevalence of eating disorders and weight control practices in Germany in 1990
      and 1997.
AB  - OBJECTIVE: To investigate whether the prevalence of bulimic behaviors and weight
      control practices changed between 1990 and 1997. METHOD: In November 1997, we
      surveyed a representative sample of 2,130 adult subjects in West Germany and
      2,155 subjects in East Germany. We asked subjects about binge eating, vomiting,
      use of laxatives, appetite suppressants and diuretics, and about dieting,
      weighing, and exercise. As the same questions had been used in a representative
      survey (N = 1,773) in autumn 1990 in West Germany, trend comparisons for
      prevalence between 1990 and 1997 are possible. RESULTS: The prevalence of severe
      eating binges twice a week dropped nonsignificantly between 1997 and 1990 from
      3.1% to 2.4% in men and from 2.3% to 1.3% in women. In men, the prevalence of
      binge eating disorder dropped nonsignificantly from 2.4% to 1.5%, the prevalence
      of bulimia nervosa from 2.1% to 1.1%. In women, the prevalence of binge eating
      disorder dropped nonsignificantly from 1.5% to 0.7% and that of bulimia nervosa
      from 2.4% to 1.1%. CONCLUSION: The prevalence of bulimic behaviors decreased
      slightly during 1990 and 1997 in the West German population.

PMID- 11285587
TI  - Postnatal depression, eating, exercise, and vomiting before and during pregnancy.
AB  - OBJECTIVE: To examine the postnatal distress and the eating, exercise, and weight
      losing behavior of women before and during pregnancy. METHOD: The subjects were
      healthy women who had given birth to a singleton healthy baby in the week before
      the study. They were drawn from two consecutive series of mothers of babies whose
      birth weights were either < or =2,500 g or >2,500 g. A total of 181 women were
      interviewed using a standardized interview modified for pregnancy and related
      behaviors. They also completed the Edinburgh Postnatal Distress Questionnaire.
      RESULTS: Regression analysis produced a final model containing variables that
      made a unique contribution to predicting the level of distress of women in the
      week following childbirth. The model accounted for 25% of the variance and
      included four variables that were associated with greater distress: fear of
      weight gain before and during pregnancy, being distracted by thoughts of food
      during pregnancy, being afraid of gaining more weight than the pregnancy would
      explain, and vomiting more frequently during the first 3-4 months of pregnancy. A
      fifth variable accounted for less distress, that is, participating in low
      intensity exercise for reasons of shape and weight during months 3-4 of
      pregnancy. Other variables associated with distress only in the preliminary
      analysis were maternal age, binge eating, and vomiting before pregnancy. The most
      distressed mothers were suffering from an eating disorder at the time of
      pregnancy. The binge and/or purge type of eating disorder was associated with
      more distress than a food restriction type. DISCUSSION: Postnatal distress is
      associated with body weight and shape concerns, with disordered eating before and
      during pregnancy, and with vomiting during pregnancy. The protective role of low
      intensity exercise during early pregnancy needs to be explored. Women with eating
      disorders should be considered at risk for postnatal problems.

PMID- 11285588
TI  - Test meal intake in obese binge eaters in relation to mood and gender.
AB  - OBJECTIVE: We assessed test meal intake in men and women with and without binge
      eating disorder (BED) in relation to mood score (Zung scale). METHODS: Eighty
      five overweight subjects (24 males and 61 females) participated; 30 subjects with
      BED and 55 without BED. Following an 8-hr fast, subjects consumed a liquid test
      meal until extremely full. RESULTS: BED subjects consumed significantly more (p
      =.009) of the test meal (1,032 g +/- 429) than the non-binge eaters (737 g +/-
      399). The men ingested more than the women (p =.002). BED subjects also had
      higher depression scores (p =.01), without differing by gender. However,
      depression scores were unrelated to test meal intakes (r = -.01). DISCUSSION: The
      larger meal intakes of the BED group may be due to the larger stomach capacity
      previously found in both bulimics and obese subjects. The findings also support
      the premise that BED, listed in the DSM-IV appendix for further study, is found
      in a distinct subgroup of overweight individuals.

PMID- 11285589
TI  - Sertraline in underweight binge eating/purging-type eating disorders: five case
      reports.
AB  - DISCUSSION: Control trials show that antidepressants are efficacious in eating
      disorders. Although selective serotonin reuptake inhibitors (SSRIs) are used in
      clinical practice, there are relatively few controlled or open trials
      demonstrating that SSRIs are effective. We report five cases of underweight women
      with binge eating/purging-type eating disorders who gained weight and had reduced
      core eating disorder behaviors in response to sertraline.

PMID- 11285590
TI  - Acute renal failure requiring dialysis after percutaneous coronary interventions.
AB  - Acute renal failure requiring dialysis is a rare but serious complication after
      percutaneous coronary interventions (PCI), associated with high in-hospital
      mortality and poor long-term survival. We have analyzed the incidence, resource
      utilization, short- and long-term outcomes, and predictors of dialysis after
      percutaneous coronary interventions. We studied 51 consecutive patients who were
      not on dialysis on admission and developed acute renal failure that required in
      hospital dialysis after PCI in comparison to the 7,690 patients who did not
      require dialysis after PCI. Patients who required dialysis were older, with a
      higher incidence of hypertension, diabetes, prior bypass surgery, chronic renal
      failure, and a significantly lower left ventricular ejection fraction. Despite
      similar angiographic success, these patients had a higher incidence of in
      hospital mortality (27.5% vs. 1.0%, P < 0.0001), non-Q-wave myocardial infarction
      (45.7% vs. 14.6%, P < 0.0001), vascular and bleeding complications, and longer
      hospitalization. At 1-year follow-up, mortality (54.5% vs. 6.4%, P < 0.0001),
      myocardial infarction (4.5% vs. 1.6%, P = 0.006), and event-free survival (38.6%
      vs. 72.0%, P < 0.0001) were significantly worse in patients who required dialysis
      compared to patients who did not. Multivariate analysis revealed in-hospital
      dialysis and an increase in baseline serum creatinine levels as the most
      important predictors of in-hospital and long-term mortality. Thus, acute renal
      failure that requires dialysis after percutaneous coronary interventions is
      associated with very high in-hospital and 1-year mortality rates and a dramatic
      increase in hospital resource utilization.

PMID- 11285591
TI  - No CAN?

PMID- 11285592
TI  - Intravascular ultrasound findings in patients with abnormal coronary flow reserve
      after stenting.
AB  - A coronary flow reserve (CFR) of 2.0 has been advocated as the endpoint for
      coronary intervention therapy. Experience shows, however, that CFR does indeed
      exceed 2.0 in many cases poststenting, while remaining below 2.0 in others. In
      this study, we assessed the clinical characteristics and IVUS findings of
      patients whose CFR remained below 2.0 after stent implantation, specifically 16
      patients with CFR below 2.0 (22 lesions, 64 +/- 9 years, 4 female), and 102
      patients with CFR above 2.0 (112 lesions, mean age 66 +/- 11 years, 22 female).
      Patient population comprised patients selected for retrospective study, but
      participants were selected on the basis of matching patient and lesion
      characteristics. The IVUS findings showed that incidence of calcified lesions and
      post-PTCA dissection of hard plaque were higher among patients with CFR < 2.0.
      Further, IVUS-obtained vascular measurements showed post-PTCA area stenosis to be
      58.7 +/- 15.2% in the CFR < 2.0 group, and 45.3 +/- 12.5% among CFR > or = 2.0
      patients (P < 0.05). These findings indicate that patients with diffuse calcified
      lesions or high post-PTCA % area stenosis, as determined by IVUS, are more likely
      to have lower CFR after stenting.

PMID- 11285593
TI  - A comparative study of light transmission aggregometry and automated bedside
      platelet function assays in patients undergoing percutaneous coronary
      intervention and receiving abciximab, eptifibatide, or tirofiban.
AB  - Platelet inhibition is central to the efficacy of glycoprotein (GP) IIb-IIIa
      antagonist therapy, but is not routinely measured during percutaneous coronary
      intervention (PCI). Data directly comparing the antiplatelet effects of these
      agents are also limited. Therefore, we compared ex vivo platelet function by
      standard light transmission aggregometry (LTA) and two automated bedside platelet
      function assays in 36 patients undergoing PCI with GP IIb-IIIa inhibitors. At
      baseline and 10 min following clinically recommended bolus and infusion of
      abciximab (0.25 mg/kg, 0.125 microg/kg/min), eptifibatide (180 microg/kg, 2
      microg/kg/min), or tirofiban (10 microg/kg, 0.1 microg/kg/min), we measured 20
      microM ADP- and 1.9 mg/mL collagen-induced platelet aggregation using LTA.
      Platelet function was also assessed using the bedside Accumetrics Ultegra-Rapid
      Platelet Function Assay (RPFA) and the Xylum Clot Signature Analyzer (CSA). The
      degree of platelet inhibition, as assessed by LTA, varied significantly between
      the clinically recommended doses of these GP IIb-IIIa antagonists. RPFA
      measurements agreed closely with LTA for abciximab, but tended to overestimate
      the degree of platelet inhibition for small molecules. CSA demonstrated
      profoundly inhibited shear-induced platelet function, but lacked sensitivity to
      discriminate between agents. These findings may have implications for the results
      of trials comparing the efficacy of these agents in patients undergoing PCI.

PMID- 11285594
TI  - IIb or not IIb: when, how, and which GP IIb/IIIa inhibitor?

PMID- 11285595
TI  - Long-term outcome of patients with proximal left anterior descending coronary
      artery in-stent restenosis treated with rotational atherectomy.
AB  - Once a first interventional procedure has failed, patients with proximal left
      anterior descending in-stent restenosis are frequently sent for surgical
      revascularization. Data on long-term outcome in selected patients with proximal
      left anterior descending in-stent restenosis treated with RA are lacking. The
      study's objective was to evaluate the long-term outcome of patients with proximal
      left anterior descending artery in-stent restenosis treated with rotational
      atherectomy. The study population is constituted by 42 patients with proximal
      left anterior descending in-stent restenosis treated with rotational atherectomy.
      Patients were followed up for 2.1 +/- 0.9 years (range, 6--54). Restenosis length
      was 16.5 +/- 9.2 mm, and restenosis was diffuse (> 10 mm in length) in 30
      (71.4%). The rotational atherectomy procedure was guided by intravascular
      ultrasound in 18 patients (42.9%). Maximum burr/artery ratio was > 0.7 in 24
      (57.1%) patients. One patient suffered a periprocedural non--Q-wave infarction,
      but no deaths, Q-wave infarction, or new target vessel revascularization occurred
      during hospitalization. There were no deaths or myocardial infarctions after
      discharge. Sixteen patients (38.1%) needed a new revascularization, but only five
      (11.9%) underwent coronary bypass grafting at the end of the follow-up (2.1 +/-
      0.9 years). The rate of surgical revascularization at 6 months, 1 year, and 3
      years was 4.8%, 7.4%, and 18.4%, respectively. The rate of new target vessel
      revascularization at 6 months, 1 year, and 3 years was 16.7%, 36.5%, and 40.5%,
      respectively. Patients with < or = 5 months since stent implantation had a
      significantly higher rate of new target vessel revascularization. Patients with
      proximal left anterior descending in-stent restenosis may be safely treated with
      rotational atherectomy. This strategy is associated with a very good long-term
      outcome, with few patients undergoing surgical revascularization.

PMID- 11285596
TI  - Direct coronary stent implantation: safety, feasibility, and predictors of
      success of the strategy of direct coronary stent implantation.
AB  - This prospective study was designed to evaluate the feasibility, safety,
      predictive factors of success, and 6-month follow-up of stent implantation
      without balloon predilatation (direct stenting) in 250 patients undergoing
      elective stent implantation. Balloon dilatation prior to stent implantation was a
      prerequisite to facilitate passage and deployment of the stent. Stent technology
      has changed tremendously, resulting in stents with improved properties, which may
      allow stent placement without prior balloon dilatation. Patients with coronary
      lesions suitable for elective stent implantation were included in this trial.
      Coronary interventions were undertaken predominantly via the transradial route
      using 6 Fr guiding catheters. Direct stent implantation was attempted using AVE
      GFX II coronary stent delivery systems. Upon failure, predilatation was
      undertaken before reattempting stent implantation. Patient data and ECGs were
      obtained from case records and from personal or telephone interviews 6 months
      after the procedure. Values were presented as mean +/- standard deviation.
      Student's t-test, two-tailed at 5% level of significance, was used to compare the
      difference of two means. Multivariate logistic regression analysis was performed
      to establish predictive factors for failure of direct stenting. Two hundred and
      sixty-six direct stent implantations were attempted in 250 patients. Direct
      stenting was successful in 226 (85%) cases. Out of 40(15%) cases where direct
      stenting failed, balloon predilatation facilitated stent implantation in 39. In
      one lesion, stent implantation was not possible despite adequate predilatation.
      Predictive factors for failure of direct stenting on multivariate analysis were
      LCx lesions (P < 0.01), complex lesions (P < 0.01), and longer stents (P <
      0.001). Minimal luminal diameter and percentage diameter stenosis of lesions in
      the successful and the failure group were not significantly different (0.94 +/-
      0.39 mm vs. 0.84 +/- 0.41 mm, P = NS, and 70.2 +/- 11.2 vs. 73.2 +/- 11.2, P =
      NS). Stent loss occurred in five (2.0%) cases, with successful retrieval in four.
      One stent was lost permanently in a small branch of the radial artery. Post
      percutaneous coronary intervention (post-PCI) myocardial infarction occurred in
      four (1.6%) patients. There were no other in-hospital events. Six-month-follow up
      information was obtained in 99% of patients. Subacute stent thrombosis was noted
      in four (1.6%) cases. Target vessel-related myocardial infarction rate was 3.2%,
      of which half was caused by subacute stent thrombosis. The overall reintervention
      rate (coronary artery bypass grafting or PCI) was 9.7%. Target lesion
      revascularization by PCI occurred in only 4.0%. At 6 months, overall mortality
      was 2.0%, of which 1.2% was due to coronary events. Direct stent implantation is
      safe and feasible in the majority of cases with low rate of complications.
      Unfavorable factors include circumflex lesion, more complex lesion morphology,
      and increasing length of stent. Severity of stenosis does not appear to be of
      predictive value. Long-term outcome is favorable with a low target lesion
      revascularization rate.

PMID- 11285597
TI  - Impact of coronary plaque morphology as assessed by IVUS computer-aided analysis
      on mechanisms of balloon angioplasty and stenting.
AB  - This study was performed in order to quantitate structural coronary plaque
      modifications after balloon angioplasty and stenting and to evaluate the impact
      of plaque morphology on the mechanisms of lumen enlargement during angioplasty.
      Plaque morphology was studied by computer-aided analysis of 60 cross-sectional
      intravascular ultrasound (IVUS) images of the target lesion in 20 patients
      undergoing percutaneous coronary angioplasty. Based on a computer-aided video
      densitometry classification of plaque morphology, three groups of plaques were
      defined based on the slope value of a fifth polynomial regression of the plaque
      gray-level distribution. In groups A and B, balloon angioplasty provided
      significant increases in lumen area (P < 0.0001) and vessel area (P < 0.05)
      without a reduction in plaque area; neither parameter increased in group C. In
      group A, stenting was associated with an additional lumen enlargement (P <
      0.0001) due to plaque reduction (P < 0.05). In groups B and C, stenting further
      increased lumen area (P < 0.0001) by improving vessel area (P < 0.001) but
      without plaque reduction. Balloon angioplasty and stenting provided a significant
      decrease in plaque area in group A as compared to groups B (P < 0.05) and C (P <
      0.01). Finally, vessel area improvement was greater in group B than in groups A
      (P < 0.01) and C (P < 0.05). The mechanisms underlying lumen enlargement after
      coronary angioplasty are highly dependent on plaque morphology as defined by an
      IVUS computer-aided analysis and may differ between balloon angioplasty and
      stenting.

PMID- 11285598
TI  - Provisional stenting for symptomatic intracranial stenosis using a
      multidisciplinary approach: acute results, unexpected benefit, and one-year
      outcome.
AB  - Percutaneous techniques have dramatically changed our approach to coronary and
      peripheral revascularization. Intracranial atherosclerosis is a highly morbid
      disease; however, techniques for revascularization are still in evolution. The
      authors comprise a multidisciplinary team of neurologists, neuroradiologists, and
      interventional cardiologists who have collaborated in treating fifteen patients
      with symptomatic intracranial stenosis who have failed medical therapy. The acute
      success rate (100%) and one-year freedom from death and stroke (93.4%) using
      balloon angioplasty and provisional stenting are encouraging. A surprising
      observation in this patient cohort was that 53% of patients had improvement or
      resolution of a deficit that was chronic and presumed to be permanent and
      irreversible. This type of chronic but reversible deficit is termed "brain
      angina". The background, rationale for a multidisciplinary team, techniques, and
      preliminary results of intracranial angioplasty with provisional stenting are
      presented.

PMID- 11285599
TI  - Lepirudin as a safe alternative for effective anticoagulation in patients with
      known heparin-induced thrombocytopenia undergoing percutaneous coronary
      intervention: case reports.
AB  - Heparin-induced thrombocytopenia (HIT) is a well-documented complication of
      heparin anticoagulation therapy. Heparin's frequent use in the cardiovascular
      population poses a significant challenge for managing patients with HIT in need
      of percutaneous coronary intervention (PCI). We describe four patients with HIT
      who successfully underwent PCI without thrombotic or hemorrhagic complications
      while on lepirudin.

PMID- 11285600
TI  - From confusion to clarity: Direct thrombin inhibitors for patients with heparin
      induced thrombocytopenia.

PMID- 11285601
TI  - Right heart catheterization in the presence of an inferior vena cava filter.
AB  - Inferior vena cava filters are being inserted with increasing frequency. When
      such patients later require right heart catheterization, brachial or jugular vein
      access is usually attempted. We describe our experience in 10 consecutive
      patients using the standard femoral approach, first assessing filter patency and
      then carefully crossing the filter using a straight guidewire. The right heart
      chambers were successfully accessed in every case. There were no complications,
      and in no case did the filter migrate or become dislodged. This technique may
      prove useful when right heart catheterization is indicated in a patient who has a
      Greenfield inferior vena cava filter.

PMID- 11285602
TI  - All roads lead to Rome.

PMID- 11285604
TI  - An unusual case of groin discomfort.
AB  - Groin complications after cardiac catheterizations are common. With the
      increasing use of mechanical hemostatic devices, cardiologists must be alert to a
      wide array of potential problems. We report an unusual complication after the use
      of a closure device.

PMID- 11285603
TI  - Use of a 0.052" Gianturco coil to embolize a persistent right superior vena cava
      following extracardiac total cavopulmonary connection.
AB  - A persistent right superior vena following extracardiac total cavopulmonary
      connection was occluded using a 0.052" Gianturco coil combined with a 3 Fr biopsy
      forceps. Controlled delivery of a 0.052" Gianturco coil is a safe and effective
      procedure to occlude a large anomalous vessel other than a large persistent
      arterial duct.

PMID- 11285605
TI  - Severe delayed thrombocytopenia associated with abciximab (ReoPro) therapy.
AB  - Acute thrombocytopenia associated with abciximab therapy has been well described,
      although the exact mechanism remains obscure. We report a case of delayed severe
      thrombocytopenia associated with abciximab therapy for percutaneous coronary
      intervention that occurred following hospital discharge. The detection of this
      phenomenon is important as it may portend heightened risk for severe or profound
      thrombocytopenia on subsequent reexposure to abciximab therapy.

PMID- 11285607
TI  - Successful stenting of a complex inferior vena cava stenosis using a modified
      sharp recanulization technique.
AB  - We describe a case of a 30-year-old male who presented with features of
      noncirrhotic portal hypertension, who was diagnosed to have inferior vena cava
      (IVC) obstruction. IVC angiogram and ultrasound study revealed a long-segment (36
      mm long), chronic total thrombotic occlusion that was dilated and stented with a
      satisfactory end result. The unique feature of this case is a modified sharp
      recanulization technique involving the use of Brokenborough (septal puncture)
      needle and Mullin dilator to create a track in such a long, chronic total
      occlusion under simultaneous ultrasound and fluoroscopic guidance.

PMID- 11285606
TI  - Retrieval of dislodged and disfigured transradially delivered coronary stent:
      report on a case using forcep and antegrade brachial sheath insertion.
AB  - We report a case of dislodged and damaged stent during transradial coronary
      procedure using 6 Fr device, which was successfully retrieved by using a forcep
      and 8 Fr antegrade brachial sheath. The disfigured and bulky stent can be
      removed, after their retrieval from the coronary circulation, using a forcep
      inserted through an 8 Fr brachial artery sheath if the radial artery is deemed
      too small to accommodate larger sheath.

PMID- 11285608
TI  - Three separate coronary artery ostia arising from the right coronary cusp: a case
      report.
AB  - Coronary artery anomalies are uncommon in the general population and most are
      asymptomatic. We report a rare congenital coronary anomaly and discuss diagnosis
      and management strategies as well as review the pertinent literature.

PMID- 11285609
TI  - Torn-off balloon tip of Z-5 atrial septostomy catheter.
AB  - Creation of atrial communication was performed in a newborn with critical aortic
      stenosis. After the success of the initial creation, balloon atrial septostomy
      using Z-5 catheter was performed. When catheter was pulled back, the tip of the
      balloon was torn off. This experience could be considered as noteworthy when
      using this catheter in patients with unusually thick atrial septum.

PMID- 11285610
TI  - Changes in coil morphology following transcatheter coil occlusion of the patent
      ductus arteriosus using a modified snare technique.
AB  - We observed a decrease in length of the Gianturco coils following transcatheter
      occlusion of the patent ductus arteriosus (PDA). Coil length was measured on
      chest radiograph within 24 hr of coil placement and compared to the length at the
      time of follow-up. Echocardiograms were also reviewed for evidence of duct
      recanalization. Twenty-seven patients met inclusion criteria. The median time to
      follow-up was 5 months (1--12 months). Twenty-four out of 27 (89%) patients had a
      decrease in coil length by 1.9 +/- 1.1 mm (P < 0.01). This was an average
      decrease of 16%. One patient had an increase in length and two patients had no
      change in coil length. Nineteen out of 27 patients had echocardiograms. Despite
      the change in coil length, there was no evidence of flow acceleration in the
      pulmonary artery or descending aorta. No patients had evidence of duct
      recanalization.

PMID- 11285611
TI  - Outcomes of transcatheter embolization in the treatment of coronary artery
      fistulas.
AB  - Thirteen children (seven male) with coronary artery fistula underwent
      percutaneous transcatheter occlusion. The age range was 8 months to 14 years
      (mean, 6.3 years). The fistulas had their origins from the right coronary artery
      (six), from the left anterior descending coronary artery (three), and from the
      left circumflex coronary artery (four). Drainage was to the right ventricle
      (seven), the right atrium (three), and one each to the pulmonary artery, left
      atrium, and superior caval vein. The fistulas were closed with coils in 10
      patients, a Rashkind double-umbrella device in 1 patient, and an Amplatzer Duct
      Occluder in 2 patients. Complete occlusion was achieved in 9 of 13 patients.
      Complications consisted of migration of coils in four and transient arrhythmias
      or changes in the resting electrocardiogram in four patients. Follow-up studies 1
      to 31 months (mean, 14.6 months) after occlusion noted only four patients with
      trivial (clinically insignificant) residual shunts. Owing to various coronary
      fistula morphologies, transcatheter occlusion requires availability of different
      embolization techniques. Short-term follow-up supports persistent clinical
      efficacy and transcatheter closure techniques as the initial form of therapy.

PMID- 11285612
TI  - Basic science review: radiotherapy for prevention of restenosis.

PMID- 11285613
TI  - Balloon atrial septostomy in end-stage pulmonary hypertension guided by a novel
      intracardiac echocardiographic transducer.
AB  - Blade and balloon atrial septostomy has been used to reduce cardiopulmonary
      symptoms and as a bridge to lung or heart lung transplant in primary pulmonary
      hypertension. Due to severe right atrial dilatation and resultant loss of
      anatomical landmarks, the procedure is technically difficult, and the reported
      postprocedure mortality rate varies between 5% and 50%. Among others, marked
      systemic desaturation and systemic hypotension presumably secondary to an
      excessively large atrial septal defect have been reported as causes of
      postprocedure death. We report a case where a novel intracardiac catheter-based
      phased-array 5.5--10 MHz transducer with spectral and color-flow Doppler
      capabilities was used to assist a balloon atrial septostomy and to obtain
      hemodynamic data in a patient with end-stage pulmonary hypertension.

PMID- 11285614
TI  - PACE, but with grace.

PMID- 11285616
TI  - Fine-needle aspiration biopsy of metastatic soft-tissue sarcomas to lymph nodes.
AB  - This paper highlights the role of fine-needle aspiration cytology (FNAC) in 15
      cases of metastatic soft-tissue sarcomas involving lymph nodes. Histopathology
      reports of the primary tumor were available in all cases. Histological diagnoses
      correlated well with the cytology reports. The most common type of sarcoma to
      involve the lymph node was embryonal rhabdomyosarcoma (6 cases), followed by
      synovial sarcoma (2 cases), leiomyosarcoma (2 cases), malignant fibrous
      histiocytoma (2 cases), fibrosarcoma (1 case), malignant peripheral nerve sheath
      tumor (1 case), and rhabdomyosarcoma (1 case). FNAC was thus helpful in the early
      diagnosis, proper staging, and management. Importantly, it obviated a lymph node
      biopsy in the majority of cases.

PMID- 11285617
TI  - Role of immunocytochemistry and DNA flow cytometry in the fine-needle aspiration
      diagnosis of malignant small round-cell tumors.
AB  - In the present study, DNA flow cytometry (FCM) and immunocytochemistry (ICC) with
      a selected panel of antibodies were performed on 51 cases of malignant tumors
      which were referred for fine-needle aspiration biopsy (FNAB) to our Department of
      Cytology for the last 2 yr. Twelve cases were diagnosed as neuroblastoma, 16 as
      Ewing's sarcoma, 2 as retinoblastoma, 5 as non-Hodgkin's lymphoma (NHL), 5 as
      rhabdomyosarcoma, 2 as peripheral neuroectodermal tumors (PNETs), and 8 as Wilms'
      tumor. Eleven of 12 neuroblastomas were diploid by FCM, and 1 was aneuploid, with
      an S-phase fraction (SPF) of 8.3%. Neuron-specific enolase (NSE) was negative in
      3 and positive in 8 cases of neuroblastoma, whereas neuroblastoma marker was
      positive in 3/11. Sixteen of 17 Ewing's sarcomas were diploid, and 1 showed
      tetraploid aneuploidy, with an SPF of 10.06%. Eight of 13 Ewing's sarcomas were
      positive for Mic-2 gene product (Ewing's marker). All 5 NHL were positive for
      leukocyte-common antigen (LCA). Three of 5 rhabdomyosarcomas were diploid, and 2
      cases showed aneuploidy. Rhabdomyosarcoma showed muscle-specific actin positivity
      in 4 and desmin positivity in 3 cases. All 3 cases of PNET were diploid and
      positive for the Mic-2 gene product, whereas NSE and vimentin were positive in 2
      cases. Both cases of retinoblastoma were diploid. Immunostaining was
      noncontributory in 1 case, and the other showed positivity for the retinoblastoma
      gene product, NSE, and chromogranin. Seven of 8 Wilms' tumors were diploid, and 1
      showed aneuploid, with an SPF of 11.13%. Seven of 8 Wilms' tumors were positive
      for cytokeratin (CK), 5 were positive for NSE, 6 were positive for epithelial
      membrane antigen (EMA), and 5 were positive for vimentin. FNAB diagnosis of
      malignant round-cell tumors is difficult only by light microscopy. Due to the
      availability of specific markers for subgrouping tumors, ICC has proved to be
      more useful these days, while DNA FCM has little diagnostic value, as most of
      them are diploid. Further ancillary studies, e.g., electron microscopy, image
      analysis, and other molecular investigations, are required to further categorize
      these tumors more precisely for better clinical management of these cases.

PMID- 11285618
TI  - Significance of lymphoglandular bodies in bone marrow aspiration smears.
AB  - The presence of lymphoglandular bodies (LGB) or Soderstrom bodies is often stated
      to be a feature of lymphoid processes. In our experience, LGB are typically
      identified in B-cell processes but not in T-cell lymphomas or myeloid leukemias.
      We reviewed 136 bone marrow aspirate smears. The number of LGB per five high
      power fields was counted, and median counts for B-cell processes, non-B-cell
      processes, myeloid leukemias, and T-cell malignancies were obtained and compared
      by the Wilcoxon rank sum test. Bone marrow aspirate smears involved with B-cell
      malignancies contained a median of 30 (range, 1-250) LGB per five high-power
      fields. Compared to myeloid leukemias (median, 11; range, 1-253) and T-cell
      malignancies (median, 7; range, 0-41), the differences were statistically
      significant (P < 0.001 and P = 0.01, respectively). While lymphoglandular bodies
      can be seen in a variety of malignant hematopoietic and nonhematopoietic
      disorders, they are found in significantly greater numbers in B-cell
      malignancies.

PMID- 11285619
TI  - Fite stain positivity in Rhodococcus equi: yet another acid-fast organism in
      respiratory cytology--a case report.
AB  - Rhodococcus equi is an aerobic Gram-positive and acid-fast coccobacillus that may
      cause cavitary pneumonia in immunocompromised hosts such as HIV-infected
      patients. Numerous Grocott's methenamine silver (GMS)-positive organisms were
      initially noted on the direct smear; a minor number of acid-fast organisms were
      seen in the Thin-Prep slide. Since the abundant mucous material with the attached
      organisms seen in conventional smears may be lost in liquid-based preparations,
      more sensitive stains such as Fite, as well as a more diligent search for
      organisms, is needed. This case illustrates the importance of careful selection
      and evaluation of special stains in sputum specimens.

PMID- 11285620
TI  - Cytodiagnosis of bile microspheroliths: a case report.
AB  - We recently observed numerous microspheroliths consisting of microscopic
      organized crystalline structures of varying shapes, sizes, and colors in a bile
      specimen from a 65-yr-old woman obtained directly from the gallbladder during a
      surgical procedure for cholecystectomy. Detection of microspheroliths could be
      very useful in the diagnostic approach to patients with recurrent pain in the
      biliary region or with acute pancreatitis of unknown origin. To date, we are
      unaware of any cytologic reports describing microspheroliths in bile.

PMID- 11285621
TI  - Fine-needle aspiration biopsy of alveolar rhabdomyosarcoma of the parotid: a case
      report and review of the literature.
AB  - The cytologic features of an alveolar rhabdomyosarcoma arising within the parotid
      gland are described. The occurrence of this neoplasm as a primary malignancy in
      the parotid gland is very rare, and the tumor is usually not included in the
      cytologic differential diagnosis of parotid tumors. The diagnosis of the current
      case was achieved by a combination of fine-needle aspiration biopsy and frozen
      sections. Realizing the difficulty of recognizing this tumor both histologically
      and cytologically, we present this case to increase the awareness of this tumor's
      occurrence within the parotid gland and other salivary glands, and to highlight
      cytomorphologic features that will aid the pathologist in making the correct
      diagnosis.

PMID- 11285622
TI  - Cytology of small-cell carcinoma of the uterine cervix in serous effusion: a
      report on two cases.
AB  - Cytologic features of 2 cases of small-cell carcinoma of the uterine cervix in
      the body fluid are described. Case 1 was a 34-yr-old woman with a stage IIA
      cervical tumor. Pleural effusion developed 6 mo after initial diagnosis. Case 2
      was a 38-yr-old woman with a stage IB tumor. Ascites was detected 11 mo after
      hysterectomy. Histologically, both cervical tumors were indistinguishable from
      small-cell carcinoma of oat-cell type in the lungs or other sites. Cytologically,
      the tumor cells in the pleural effusion of case 1 had characteristic features of
      small-cell carcinoma, including nuclear molding. However, almost all tumor cells
      in the ascites of case 2 showed a single-cell pattern mimicking malignant
      lymphoma. Mitotic figures and karyorrhetic bodies were occasionally seen. Nuclear
      molding was rarely identified. Small-cell carcinoma should be included in the
      differential diagnosis of malignant effusions containing lymphoma-like cells.

PMID- 11285623
TI  - Cytologic clue of so-called nodular histiocytic hyperplasia of the pleura.
AB  - So-called "nodular histiocytic hyperplasia" (NHH) is a benign histiocytic lesion
      caused by mechanical irritation, inflammation, and tumor. Frequently, it has been
      confused with mesothelial lesions and other malignant neoplasms. The diagnostic
      clue is proliferating cells in the lesion showing diffuse, strong
      immunoreactivity against the histiocytic marker, CD68. Recently, we encountered a
      case of so-called NHH of the pleura and confused it with various malignant
      neoplasms on histologic examination. An 80-yr-old Korean female presented with
      ascites, pleural effusions, and nodules on the pleural base. Both ascites and
      pleural effusion tapping smears displayed moderate cellularity, vaguely nodular
      cellular aggregates mainly composed of mononuclear cells with bland morphology,
      entrapped mesothelial cells, and background lymphocytes. Pleural biopsy
      demonstrated vaguely nodular, compact cellular aggregates of reactive histiocytes
      which were immunoreactive against CD68. Based on our case, cytologic examination
      as well as immunohistochemical study should be stressed in the case of so-called
      NHH. They can provide us more credible morphologic clues to reach a more accurate
      diagnosis than histologic examination alone, and we can avoid invasive procedures
      or unnecessary therapies to patients. To our best knowledge, this is the first
      report describing the cytologic features of so-called NHH in the English-language
      literature.

PMID- 11285624
TI  - What is the role of cytopathologists in stereotaxic needle biopsy diagnosis of
      nonpalpable mammographic abnormalities?
AB  - The popularity of screening mammography has led to increased detection of
      mammographic lesions that require pathologic diagnosis. Stereotaxic needle biopsy
      techniques to sample such lesions can be used to either identify those lesions
      that require excision from those that can be followed, or to confirm a
      mammographic impression of malignancy prior to excision. Stereotaxic core biopsy
      (SCBX) and stereotaxic fine needle aspiration (SFNA) have rarely been directly
      compared. For this review we undertook a uniform re-analysis of the data that was
      presented in the published studies of SFNA and/or SCBX. The main endpoint was the
      negative predictive value (NPV) that measures the frequency that a benign
      diagnosis is truly benign. There was variability in NPV (likely due to sampling
      methods) and specific aspects of sampling techniques are discussed. The NPV was
      compared to indicators of selection of lesions to biopsy (frequency of invasive
      cancer in the study population), mammographic characteristics (masses or
      microcalcifications), and the reported nondiagnostic rates. The general
      conclusion is that SFNA and SCBX are equivalent in accuracy, with considerable
      variability that reflects the types of lesions that are selected for biopsy and
      the thoroughness of sampling. For SFNA studies, nondiagnostic rates were
      inversely related to NPV, and therefore have clinical implications. This was not
      shown for SCBX studies, and probably reflects an inability to correctly identify
      non-representative tissue biopsies. The main advantage for including cytologic
      methods with stereotaxic breast biopsy is immediate sample assessment, and this
      advantage can also be applied to core needle procedures.

PMID- 11285625
TI  - Significance of histiocytes in cervical smears from peri/postmenopausal women.
AB  - Histiocytes in cervicovaginal smears from peri- or postmenopausal women have been
      viewed as a potential indicator of endometrial neoplasia, but recent studies have
      refuted that view. This study further defines the clinical significance of such
      findings. All cervical smears were selected from women (< or = 50 yr) in whom the
      presence of histiocytes was mentioned; pertinent clinical history, follow-up
      information, and selected slides were reviewed. Among 105,225 total
      cervicovaginal smears from a 3.5-yr period, 106 smears from 103 women were
      identified. Forty-two patients (41%) were on hormone replacement therapy (2 on
      tamoxifen), and 23 (22.3%) patients experienced vaginal bleeding, all of whom had
      biopsy or cytology follow-up. Ten (9.6%) patients had no follow-up, 35 (32%) had
      repeat smears only, and 58 (56.3%) had endometrial/endocervical sampling. In 28
      patients, the index smear was categorized as other than within normal limits or
      benign cellular changes; of these, 24 had subsequent tissue sampling and 4 had
      cytology follow-up. Of the patients with tissue sampling, 51 (84%) had benign
      findings (including polyps), 2 (3.5%) had hyperplasia, and 5 (10%) had
      adenocarcinoma. All 5 patients with adenocarcinoma had endometrial glandular
      cells on the smear, and 4 had vaginal bleeding. One patient with hyperplasia had
      vaginal bleeding, and the other was on tamoxifen and had endometrial glandular
      cells on the smear. None of the patients having only histiocytes on their smears
      and no clinical symptoms or risk factors had endometrial adenocarcinoma or
      hyperplasia. These findings support the conclusion that the presence of
      histiocytes alone on cervicovaginal smears from peri- or postmenopausal women is
      nonspecific and of no major clinical significance in the absence of other
      clinical or cytologic findings.

PMID- 11285626
TI  - Prevalence and epidemiologic correlates of atypical squamous cells of
      undetermined significance in women at low risk for cervical cancer.
AB  - Our aim was to determine the prevalence and epidemiologic correlates of atypical
      squamous cells of undetermined significance (ASCUS) in a population at low risk
      for cervical cancer in Porto Alegre, Brazil. Sociodemographic data and
      gynecological and obstetrical history from 977 women screened at an outpatient
      clinic were recorded. Specimens were collected for Papanicolaou cervical
      cytology, colposcopy, and biopsy (if indicated). Sixty-two (6.3%) patients
      presented ASCUS, 21 (2.1%) presented low-grade squamous intraepithelial lesions,
      and 6 (0.6%) presented high-grade lesions. Presence of human papillomavirus (HPV)
      DNA in cervical cells (odds ratio (OR) = 1.57; confidence interval (CI) 95% =
      1.11-2.23), history of HPV infection (OR = 3.12; CI 95% = 1.22-7.96), and
      becoming sexually active at 18 yr or younger (OR = 1.70; CI 95% = 1.15-2.51) were
      independently associated with ASCUS. ASCUS patients reported HPV infections and
      presented HPV DNA in cervical cells more often than did patients with normal
      cytology; therefore, they should be carefully monitored to ensure early detection
      of cancer precursor lesions and prevention of cervical cancer.

PMID- 11285627
TI  - PNET-like features of synovial sarcoma of the lung: a pitfall in the cytologic
      diagnosis of soft-tissue tumors.
AB  - Fine-needle aspiration (FNA) cytology of soft-tissue tumors is evolving. As more
      experience is gained, we are becoming aware of potential pitfalls. We describe 2
      cases of synovial sarcoma of the lung, primary and metastatic, in patients who
      had FNA biopsy performed on a lung mass. The cytologic smears showed extremely
      cellular groups of malignant small round cells, intersected by small blood
      vessels, with numerous loose single cells, in a background of macrophages and
      mature lymphocytes. The tumors displayed monomorphic cells forming rosettes and
      displaying occasional mitoses. A diagnosis of neuroendocrine tumor/primitive
      neuroepithelial tumor (PNET) was suspected. Furthermore, this suspicion was
      supported by immunohistochemical stains, which showed positivity for a
      neuroendocrine marker, Leu 7 (case 1), and for a neural marker, CD 99 (O 13 or
      HBA 71) (both cases); and negativity for cytokeratins (case 1). The resection
      specimen of case 1 had mostly tightly packed small round cells, with occasional
      rosettes, similar to the FNA biopsy, and focal areas composed of spindle cells,
      organized in a focal fibrosarcoma-like and hemangiopericytoma-like pattern. A
      balanced translocation between chromosomes X and 18, demonstrated by both
      karyotyping and fluorescent in situ hybridization (FISH), enabled us to make a
      diagnosis of synovial sarcoma, which was histologically classified as poorly
      differentiated. Case 2 was a metastatic biphasic synovial sarcoma of the arm,
      with a prominent epithelial component. Synovial sarcoma, when composed mainly of
      small round cells on cytologic smears, is a great mimicker of neuroendocrine/PNET
      tumors, with light microscopic and immunohistochemical overlap. Awareness of this
      potential pitfall may aid in preventing a misdiagnosis. Its recognition is of
      major concern, especially for the poorly differentiated variant, because it is
      associated with a worse prognosis.

PMID- 11285628
TI  - Intraoperative diagnosis of tanycytic ependymoma: pitfalls and differential
      diagnosis.
AB  - Smear preparations have become increasingly popular in the intraoperative
      assessment of central nervous system pathology. The cytological features of a
      histologically proven tanycytic ependymoma are presented with the pitfalls and
      differential diagnosis. The smear preparation showed a glial neoplasm composed of
      cells with long, bipolar glial processes and oval to spindle-shaped nuclei
      resembling those seen in pilocytic astrocytoma smears. The smear characteristics
      of an ependymoma usually show remarkably uniform round-to-oval nuclei, fluffy
      glial processes, and a perivascular nuclear-free zone (pseudorosetting). None of
      these features were present in our case. The accompanying frozen section showed a
      fascicular spindle-cell tumor that resembled a schwanomma, a commonly reported
      misinterpretation of the histology of tanycytic ependymomas on frozen sections.
      Careful attention to the radiological findings, the surgeon's impression, and the
      intraoperative smear preparation details should allow one to include this
      uncommon entity in the differential diagnosis of spinal neoplasms.

PMID- 11285629
TI  - Accuracy of the smear technique in the cytological diagnosis of 650 lesions of
      the central nervous system.
AB  - The authors analyzed the results of 650 lesions of the central nervous system
      submitted to intraoperative cytological diagnosis by the smear technique.
      Cytological and paraffin section diagnoses were compared. The following
      statistical values were obtained: accuracy of 97.3%, sensitivity of 97.9%,
      specificity of 95%, positive predictive value of 99.1%, and negative predictive
      value of 89.6%. The authors comment on their main pitfalls using this cytological
      diagnostic procedure.

PMID- 11285630
TI  - Fine-needle aspiration of pleomorphic lipoma.

PMID- 11285631
TI  - Cytology of Rosai-Dorfman disease.

PMID- 11285632
TI  - Infarction of pleomorphic adenoma: a rare complication of fine-needle aspiration
      obscuring definitive diagnosis.

PMID- 11285633
TI  - [Outbreak of bovine virus diarrhea on Dutch dairy farms induced by a bovine
      herpesvirus 1 marker vaccine contaminated with bovine virus diarrhea virus type
      2].
AB  - On 23 February 1999, the Dutch Animal Health Service advised all Dutch veterinary
      practices to postpone vaccination against bovine herpesvirus 1 (BHV1)
      immediately. The day before severe disease problems were diagnosed on four dairy
      farms after vaccination with the same batch of BHV1 marker vaccine. Using
      monoclonal antibodies, bovine virus diarrhoea virus (BVDV) type 2 was found in
      the vaccine batch. This paper describes an outbreak of BVDV type 2 infection
      caused by the use of a batch of modified live BHV1 marker vaccine contaminated
      with BDVD. Sources of information used were reports of farm visits, minutes of
      meetings, laboratory results, and oral communications from the people involved.
      The first symptoms of disease were observed on average six days after
      vaccination. Morbidity was high on 11 of the 12 farms. On five farms more than
      70% of the animals became ill, while on one farm no symptoms could be detected.
      During the first week after vaccination, feed intake and milk production
      decreased. During the second week, some animals became clinically diseased having
      nasal discharge, fever, and diarrhoea. At the end of the second week and at the
      start of the third week, the number of diseased animals increased rapidly, the
      symptoms became more severe, and some animals died. Mortality varied among herds.
      Necropsy most often revealed erosions and ulcers of the mucosa of the digestive
      tract. In addition, degeneration of the liver, hyperaemia of the abomasum, and
      swollen mesenterial lymph nodes and swollen spleen were found. On 11 of the 12
      farms all animals were culled between 32 and 68 days after vaccination after an
      agreement was reached with the manufacturer of the vaccine. This was the third
      outbreak of BVD in cattle after administration of a contaminated vaccine in the
      Netherlands. The possibilities to prevent contamination of a vaccine as a
      consequence of infection of fetal calf serum with BVDV are discussed. Improvement
      of controls to prevent contamination before and during vaccine production, and
      improvement of the monitoring of side-effects is necessary.

PMID- 11285634
TI  - [Did vaccination with an infectious bovine rhinotracheitis (IBR) marker vaccine
      on thirteen cattle farms give rise to chronic wasting among dairy cattle?].
AB  - At the end of May 1999 the author was asked by the Dutch Animal Health Service
      (GD) to evaluate problems with 'chronic wasting' cows on 13 farms. The cows were
      thought to have become ill after vaccination with an IBR marker vaccine. On nine
      farms a number of cows aborted shortly after vaccination. On eight farms lameness
      was a problem, as was mastitis. Diarrhoea occurred on four farms. A number of
      farms had problems with stillbirth, subfertility, abomasal displacement, and
      decreasing body condition. It was concluded that the abortions, stillbirth, and
      weak calves at birth in the first weeks after vaccination might be associated
      with the vaccination. However, the author found no indication that the other
      problems were associated with the vaccination. This was because the symptoms on
      the 13 farms were not uniform, and many of the herds already had problems before
      the herd was vaccinated. The 'chronic wasting' problem cannot be attributed to
      vaccination with the IBR marker vaccine. 'Chronic wasting' concerns a
      multifactorial complex of diseases, and has always been present, but has
      increased in incidence in the last years as a result of 'Holsteinization', a very
      high milk production, longer periods of housing indoors (and in many cases
      insufficient quality of the stable and cubicles), a too high work load, and
      insufficient management.

PMID- 11285635
TI  - [Analysis of symptoms associated with bovine herpesvirus 1 vaccination].
AB  - Between 1 May 1998 and 22 February 1999, it was compulsory for Dutch cattle
      farmers to take measures against bovine herpesvirus 1 (BHV1). Cattle on farms
      that were not certified as infectious bovine rhinotracheitis (IBR)-free had to be
      vaccinated twice a year. During the vaccination programme, both farmers and
      veterinarians reported side-effects of the vaccine. These reports were collected
      by the Stichting IBR/BVD Schade (SIS; Foundation for IBR/BVD Damage) in order to
      draw up a damage report. In 1999 in total 6977 cattle farmers lodged complaints
      which they considered to be related to the vaccination against BHV1. On these
      farms, 15,150 herd vaccinations had been performed, 10,269 of which were
      associated with one or more symptoms. During the compulsory vaccination period,
      13% of the herd vaccinations led to symptoms and complaints. In March 1999, a
      number of vaccine batches were found to be contaminated with bovine virus
      diarrhoea (BVD) virus. For the purposes of this analysis, a 'known contaminated'
      herd vaccination was defined as one in which at least one 'known contaminated'
      batch or lot of vaccine was used. In total, 987 of 1007 herds vaccinated with
      'known contaminated' vaccines developed one or more symptoms compatible with
      acute BVD. There were no commonly seen combinations of symptoms. For this reason,
      and because the start and end dates were not reported for 55% of the symptoms, it
      was not possible to detect a symptom pattern. Therefore there were no 'suspect'
      batches of vaccine which, although not contaminated with BVD virus, gave rise to
      symptoms. The number of BVD symptoms was determined for those herds with
      vaccination-related symptoms. There was no difference in the distribution
      frequency between batch numbers or between 'known contaminated' batches and 'non
      suspect' batches. The farmers' definition of chronic wasting was used in this
      investigation, with the inevitable large differences in definition. The symptom
      chronic 'wasting' was reported for 3209 of the 10,269 herds with vaccination
      related symptoms. On 161 farms (164 herd vaccinations) 'chronic wasting'
      accounted for more than 20% of the symptoms. As expected, other symptoms were
      reported in addition to wasting. The symptom 'chronic wasting' was reported more
      often on forms where a 'known contaminated' vaccine was used. Inactivated vaccine
      was used for 154 herd vaccinations. In 34 cases, one or more symptoms of acute
      BVD were reported. The frequency was the same as that for live vaccines. The
      frequency of reported symptoms tended to be lower with the inactivated vaccine.
      On the basis of the SIS data, no relationship was found between vaccine batch and
      reported symptoms. This may be because (i) the classification of a vaccine as
      'known contaminated', 'non-suspect', and 'not known' may not have been in keeping
      with the real status of the vaccine, (ii) farmers may have reported symptoms
      selectively, and (iii) there is no relationship with vaccination against BHV1.

PMID- 11285636
TI  - [Prevalence of chronic wasting in Dutch dairy herds with a history of chronic
      health problems].
AB  - The prevalence of chronic wasting in cattle in March and April 2000 was studied
      on 218 dairy farms with a history of health problems accompanied by wasting,
      following reports in the media suggesting that chronic wasting was a substantial
      problem on Dutch dairy farms. A telephone call revealed that the health problems
      had resolved on 41 farms; 16 of these farms had culled all cattle. Two farmers
      refused co-operation. On the remaining 175 farms the animals were inspected and
      was completed a questionnaire. A high percentage of culling for of health reasons
      (on average 18.1% of young stock and adult cattle) and an increased mortality
      rate (4.8%) were reported on the farms visited. In only two of the 175 inspected
      herds, more than 20 percent of cattle were found showing signs of wasting. These
      two herds were identified as 'chronic wasting herds'. The prevalence of such
      herds was low in this study. Consequently, it is likely that there were very few
      'chronic wasting herds' among the whole Dutch dairy population in March/April
      2000.

PMID- 11285637
TI  - [Clinical findings of cows who originated from dairy herds with chronic wasting
      disease].
AB  - Since Spring 1999, a number of dairy farms have reported problems with wasting in
      cattle. After calving, the physical condition of the cows deteriorated for
      reasons unknown. Chronic wasting is also associated with disorders such as
      lameness, abortion, endometritis, mastitis, and respiratory problems. Between
      April 1999 and March 2000, 19 cows were sent to the Faculty of Veterinary
      Medicine for further investigation of the chronic wasting. Clinical and
      pathological investigations resulted in a broad range of diagnoses such as
      mastitis, abomasal displacement, and claw disorders. The latter, characterised
      severe laminitis, were predominant and could explain a number of secondary
      symptoms (inflammation of the bursa, metastatic processes). There were no clear
      consistent changes compatible with a certain agent, with the exception of one
      case in which a virus was shown to be the causative agent. The results indicate
      that wasting disease is not a distinct entity but is characterized by a broad
      range of diseases in which acute laminitis may be the original problem. The
      disease profile of chronic wasting disease is very similar to that of 'concrete
      disease' described by Rebhun in 1995.

PMID- 11285638
TI  - [Detection of bovine virus diarrhea virus in a live bovine herpes virus 1 marker
      vaccine].
AB  - In February 1999, 12 Dutch herds were vaccinated with a live bovine herpesvirus 1
      vaccine from which bovine virus diarrhea virus (BVDV) could be isolated. All
      vaccine batches that were on the Dutch market and that had not yet reached the
      expiry date were tested for BVDV. In total, seven of 82 batches tested were found
      positive. Batch numbers TX3607, VB3914, VB3915, VB4046, TW3391, and TV3294 were
      positive for BVDV type 1, and batch number WG4622 was positive for BVDV type 2.
      This latter batch induced clinical signs of BVDV in an animal experiment with
      susceptible animals.

PMID- 11285639
TI  - [Comparison of performance of dairy herds that were or were not vaccinated with a
      bovine herpes virus 1 marker vaccine in 1998].
AB  - This study analysed the effects of the use of bovine herpesvirus 1 (BHV1) marker
      vaccine on the performance of dairy cattle. In Spring of 1999, vaccination of 12
      herds with the BHV1 marker vaccine resulted in severe animal health problems and
      mortality. The vaccines used on these farms were all from a batch that appeared
      to be contaminated with bovine virus diarrhoea virus type 2. This led to a
      general call to farmers and veterinary practitioners to report side-effects of
      this vaccine. As a result, more than 7000 farmers reported symptoms. The
      information was obtained by means of a questionnaire; there was no control group.
      To determine the effects of the use of the marker vaccine, it was necessary to
      perform a study based on objectively acquired information. The information
      collected by the Royal Dutch Cattle Syndicate and the office of Identification
      and Registration was complied into herd indices on production, udder health,
      reproduction, and culling. Two groups of dairy farms that had used the BHV1
      marker vaccine (attenuated and inactivated vaccine) were compared with farms that
      were certified BHV1-free. The analyses were performed based on intra-herd
      comparisons, meaning that per herd each index calculated over a certain period of
      time after the use of the marker vaccine was compared to a similar period of time
      prior to the use of the marker vaccine. A total of 144 comparisons were made.
      Seven comparisons were statistically significant. In two comparisons, the results
      were in favour of the BHV1-free farms and in five comparisons, the result were in
      favour of the vaccinated farms. Thus use of the BHV1 marker vaccine could not be
      proven to affect herd performance. The sensitivity of the tests was very high, so
      with a high level of probability even very small differences in indices between
      groups would have been detected.

PMID- 11285640
TI  - [Management and herd performance of dairy herds with and without chronic wasting
      disease].
AB  - 'Chronic wasting' in cattle acquired a special meaning in the Netherlands in
      1999. It was used to define animal health problems that were thought to be
      associated with the use of bovine herpesvirus 1 marker vaccine. Criteria have not
      been set by which an objectively independent inventory of the problems could be
      made. The objective of this study was to determine management factors associated
      with the problem of 'chronic wasting' prior to the use of the BHV1 marker
      vaccine. Knowledge about these factors could be helpful for generating additional
      hypotheses about the aetiology of chronic wasting in cattle. A total of 188 farms
      participated in the study, of which 94 had severe problems with chronic wasting.
      The other half consisted of control farms matched with the case farms that did
      not report problems after the use of the BHV1 marker vaccine. Data analyses were
      performed over the period before (and not at the time of) 'chronic wasting'
      problems. Data were collected from various sources. A questionnaire was used to
      collect information on farm management practice. In addition, information on
      laboratory submissions for 1996 to 1998, animal movements in 1998, roughage
      analyses of 1997 and 1998, expenses for animal health in 1998, and herd
      performance in 1995 to 1999 was collected. In the analyses, a distinction was
      made between information obtained objectively and subjectively. Herds with
      problems of 'chronic wasting' were larger than herds without wasting problems
      (animals, surface) but not more intensively managed. 'Wasting' herds had a lower
      performance in terms of fertility and udder health. In addition, these herds had
      more contact with other herds through the purchase of animals. There were no
      differences in farm management practices related to disease control and
      prevention. Additional studies are required with regard to the patho-physiology
      of chronic wasting cows. The role of herd size needs more study.

PMID- 11285641
TI  - [Vaccination of calves with contaminated batches of bovine herpes virus 1
      vaccines did not result in infection with bovine virus diarrhea virus].
AB  - The aim of the experiment was to study whether bovine herpesvirus 1 (BHV1) marker
      vaccine batches known to be contaminated with bovine virus diarrhoea virus (BVDV)
      type 1 could cause BVD in cattle. For this purpose, four groups of cattle were
      used. The first group (n = 4 calves, the positive control group), was vaccinated
      with vaccine from a batch contaminated with BVDV type 2. The second group (n = 4
      calves, the negative control group), was vaccinated with vaccine from a batch
      that was not contaminated with BVDV. The third group (n = 39 calves), was
      vaccinated with a vaccine from one of four batches contaminated with BVDV type 1
      (seronegative experimental group). The fourth group (n = 6 seropositive heifers),
      was vaccinated with a vaccine from one of three batches known to be contaminated
      with BVDV type 1. All cattle were vaccinated with an overdose of the BHV1 marker
      vaccine. At the start of the experiment, all calves except those from group 4
      were seronegative for BVDV and BHV1. The calves from group 4 had antibodies
      against BVDV, were BVDV-free and seronegative to BHV1. After vaccination, the
      positive control calves became severely ill, had fever for several days, and BVDV
      was isolated from nasal swabs and white blood cells. In addition, these calves
      produced antibodies to BVDV and BHV1. No difference in clinical scores of the
      other groups was seen, nor were BVDV or BVDV-specific antibody responses detected
      in these calves; however, they did produce antibodies against BHV1. The remainder
      of each vaccine vial used was examined for the presence of infectious BVDV in
      cell culture. From none of the vials was BVDV isolated after three subsequent
      passages. This indicates that BVDV was either absent from the vials or was
      present in too low an amount to be isolated. Thus vaccination of calves with
      vaccines from BHV1 marker vaccine batches contaminated with BVDV type 1 did not
      result in BVDV infections.

PMID- 11285642
TI  - [The effect of a high dose bovine herpes virus 1 marker vaccine in pregnant
      heifers: virological, bacteriological, immunological, and pathological findings].
AB  - To determine a possible relationship between the compulsory vaccination against
      bovine herpesvirus 1 (BHV1) and cattle wasting disease, the effects of BHV1
      vaccination on heifers were investigated. Twenty heifers in the third trimester
      of pregnancy were randomly allotted to a vaccine and a control group. The vaccine
      group was vaccinated twice with a 50-fold dose of BHV1 vaccine and the control
      group was inoculated with the diluent. The experiment was performed double blind.
      After vaccination, the cows were examined daily and condition scores were
      determined weekly. Blood, milk, and faeces samples were collected weekly for
      virological, bacteriological, and immunological investigation. The heifers were
      euthanized either 9 or 13 weeks after the first inoculation and pathological,
      virological, and bacteriological examination was performed. No differences were
      detected between the vaccine group and the control group. No concurrent
      infections were detected and there were no indications of immunosuppression after
      vaccination. No relationship between the BHV1 vaccination and wasting disease in
      cattle was detected.

PMID- 11285643
TI  - [Vitamin B12 supplementation and milk production on farms with 'chronic wasting'
      cattle].
AB  - From early 1999 onwards, cattle health problems accompanied by chronic wasting of
      unknown aetiology were reported on a number of dairy farms. An association
      between these health problems and the compulsory use of gE-negative marker
      vaccines against bovine herpesvirus 1 was presumed by farmers. On one dairy farm
      an increased milk production of 50% was reported within a few days after
      parenteral vitamin B12 treatment. Therefore, the current study was designed to
      determine the effect of parenteral vitamin B12 treatment on the milk production
      of dairy herds with wasting cattle. A randomized blind trial was performed in
      five problem herds and two control herds. On each farm five lactating cows were
      injected intramuscularly with 20 mg vitamin B12 and paired with five untreated
      lactating cows. The milk production of treated and untreated animals was measured
      for 19 days following treatment and compared to pre-treatment production. No
      effect of vitamin B12 treatment on milk production was established on either
      problem farms or control farms. Neither was a difference detected in the response
      to vitamin B12 treatment between problem herds and control herds. In a second
      experiment, parenteral vitamin B12 treatment was applied in three problem herds
      by local veterinary practitioners. The results of this experiment were in line
      with the results of the first experiment.

PMID- 11285644
TI  - [Possibilities for further research of chronic wasting in dairy cows].
AB  - In this study, we reviewed the research that has been conducted in relationship
      with the problem of 'chronic wasting' in dairy cows in the Netherlands as was
      experienced during 1998 and 1999. Emphasis was drawn towards three aspects of
      this 'chronic wasting'; the definition, the magnitude, and the possible cause or
      causes. It appeared that a clear, objective definition of 'chronic wasting' in
      cows, and of farms with a problem of 'chronic wasting' cows is still lacking.
      Furthermore, the incidence (of the problem) was restricted to approximately 150
      dairy farms at most. Currently, no farms with 'chronic wasting' cows are known.
      Combined with the uncertainty in the definition, this will hamper future
      research. Many of the studies were related to the hypothesis that the vaccination
      with the BHV1 marker vaccine had caused 'chronic wasting' in the cows. None of
      the results, however, substantiated this hypothesis. Other possible causes have
      hardly been investigated and further research would be needed to evaluate the
      role of nutrition, infectious agents, and genetics. However, due to the waning of
      the phenomenon, the availability of data and controls will be limiting.

PMID- 11285645
TI  - [Chronic wasting, a consequence of subacute ruminal acidosis?].

PMID- 11285646
TI  - [An alternative view. Mycotoxins and mycoses].

PMID- 11285647
TI  - [What lessons are to be learned? Quality of animal vaccines].

PMID- 11285648
TI  - [The cause of chronic wasting: what can be concluded?].

PMID- 11285649
TI  - [Chronic wasting?].

PMID- 11285650
TI  - [Chronic wasting: what can we learn from it?].

PMID- 11285651
TI  - [Chronic wasting disease. What do we know for sure at this point?].

PMID- 11285652
TI  - [Veterinarians must prevent infection in other small animals].

PMID- 11285653
TI  - On getting it all together.

PMID- 11285654
TI  - Malpractice: provider risk or consumer protection?
AB  - The National Practitioner Data Bank (NPDB) began operation in September 1990 as a
      clearinghouse for adverse action, licensure, and malpractice information in an
      effort to protect consumers and promote quality in health care. This study
      analyzed 66,107 and 1291 records of payments made for 50,396 physicians and 1218
      nurses, respectively, from 1994 through 1998, to describe characteristics,
      trends, and risk factors of malpractice payment for physicians and nurses. The
      median payments, more often settlements paid by insurance companies than
      judgments in courts of law, were higher for physicians than for nurses. Mean
      payments were higher for residents than for non-resident physicians; median
      payments for residents were slightly lower than other physicians when adjusted
      for number of providers included in the payment. On the state level, correlation
      analyses suggested a significant positive association between the nurse rate of
      malpractice payments that were made and median per capita income, number of
      physicians per 1000 residents, and number of attorneys per 1000 residents;
      analysis revealed a significant negative association between this rate and the
      percentage of residents residing in rural areas and the number of nurses per 1000
      residents. Although findings suggested that payment trends remained stable, there
      was great regional variation in the risk of malpractice payment for both
      physicians and nurses. The physician risk ranged from a low of 0.73% per
      physician per year in Alabama to a high of 3.7% in Wyoming, and the nurse risk
      ranged from a low of 0% per nurse per year in Vermont to a high of 0.075% in the
      District of Columbia. If the quality of health care provided by physicians and
      nurses does not vary geographically in the United States, then such a great
      discrepancy seems to challenge the notion that the risk of malpractice litigation
      consistently promotes the quality of health care.

PMID- 11285655
TI  - Commentary: applying hospital quality indicators to clinical practice.
AB  - Hospitals use various methods to establish performance benchmarks. This may
      include cooperative data shared between organizations to allow broad, general
      comparisons. These can, however, be misinterpreted as representing standards of
      patient care. In the authors' institution, a more complete examination was made
      of one of these quality indicators when it appeared quality indicator standards
      were in conflict with standards of patient care. The authors conclude that
      quality indicators are valuable when screening a hospital, just as we utilize
      screening tests to identify patients at potential risk. Neither should we apply
      broad quality indicators as standards of care without a full understanding of
      their strengths and weaknesses and the foundation on which they are built.

PMID- 11285656
TI  - California provider group report cards: what do they tell us?
AB  - The objective of this study was to perform a practical assessment of publicly
      reported data from 4 reports on California provider groups through the eyes of
      the consumer. The study compared performance indicator content and rating
      methodologies, examined the degree of correlation in provider group performance
      on indicators common to 2 or more reports, and assessed the level of concordance
      among summary ratings of performance. Comparative analyses revealed significant
      variation in performance indicator content, data sources, and rating
      methodologies. Spearman correlation analysis revealed highly correlated group
      performance on patient satisfaction and member-requested group transfers, poorly
      correlated performance on breast and cervical cancer screening, and moderately
      correlated performance on state and regional average scores. Summary ratings
      applied to these data were only moderately correlated. These findings suggest
      that competing California provider group report cards produce inconsistent
      messages about provider quality and may create barriers to use, comprehension,
      and reliance upon quality information among consumers and other potential users.

PMID- 11285657
TI  - Brief communication: detecting depression: providing high quality primary care
      for HIV-infected patients.
AB  - Depression is common among HIV-infected patients, but little is known about risk
      factors for depression in this population. Several studies before protease
      inhibitors became available have reported inconsistent associations between
      depression and disease severity. Delivering high quality HIV care includes
      adequate detection and treatment of depression. The objective of this study was
      to describe the prevalence and correlates of depression among a contemporary
      group of HIV-infected patients. The setting and design for the study was a chart
      abstraction for HIV-infected patients in a primary care practice in Boston, Mass,
      in June 1997. Among 275 HIV-infected patients, depression was documented in 147
      patient charts (53%), half of whom (n = 73, 27%) also received antidepressant
      medications. We used multivariable logistic regression to identify risk factors
      for depression among patients with both a chart diagnosis of depression and
      current antidepressant medication use. We observed increased risk of depression
      among patients with a history of substance use (odds ratio 2.7, 95% confidence
      interval 1.5-4.7), recent medical hospitalization (2.6, 1.4-5.0), and homosexual
      risk behavior (2.1, 1.1-4.2). Depression remains a common problem for HIV
      infected patients, particularly among those with history of substance abuse,
      medical hospitalization, or homosexual risk behavior. Routine screening for
      depression in this population with special attention to those at higher risk may
      offer opportunities for earlier diagnosis and treatment.

PMID- 11285658
TI  - Is estimating maternal mortality useful?

PMID- 11285659
TI  - Blindness: a global priority for the twenty-first century.

PMID- 11285660
TI  - An epidemic of blindness: a consequence of improved HIV care?

PMID- 11285661
TI  - Estimates of maternal mortality for 1995.
AB  - OBJECTIVE: To present estimates of maternal mortality in 188 countries, areas,
      and territories for 1995 using methodologies that attempt to improve
      comparability. METHODS: For countries having data directly relevant to the
      measurement of maternal mortality, a variety of adjustment procedures can be
      applied depending on the nature of the data used. Estimates for countries lacking
      relevant data may be made using a statistical model fitted to the information
      from countries that have data judged to be of good quality. Rather than estimate
      the Maternal Mortality Ratio (MMRatio) directly, this model estimates the
      proportion of deaths of women of reproductive age that are due to maternal
      causes. Estimates of the number of maternal deaths are then obtained by applying
      this proportion to the best available figure of the total number of deaths among
      women of reproductive age. FINDINGS: On the basis of this exercise, we have
      obtained a global estimate of 515,000 maternal deaths in 1995, with a worldwide
      MMRatio of 397 per 100,000 live births. The differences, by region, were very
      great, with over half (273,000 maternal deaths) occurring in Africa (MMRatio: >
      1000 per 100,000), compared with a total of only 2000 maternal deaths in Europe
      (MMRatio: 28 per 100,000). Lower and upper uncertainty bounds were also
      estimated, on the basis of which the global MMRatio was unlikely to be less than
      234 or more than 635 per 100,000 live births. These uncertainty bounds and those
      of national estimates are so wide that comparisons between countries must be made
      with caution, and no valid conclusions can be drawn about trends over a period of
      time. CONCLUSION: The MMRatio is thus an imperfect indicator of reproductive
      health because it is hard to measure precisely. It is preferable to use process
      indicators for comparing reproductive health between countries or across time
      periods, and for monitoring and evaluation purposes.

PMID- 11285662
TI  - Comparison of two azithromycin distribution strategies for controlling trachoma
      in Nepal.
AB  - OBJECTIVE: The study compares the effectiveness of two strategies for
      distributing azithromycin in an area with mild-to-moderate active trachoma in
      Nepal. METHODS: The two strategies investigated were the use of azithromycin for
      1) mass treatment of all children, or 2) targeted treatment of only those
      children who were found to be clinically active, as well as all members of their
      household. FINDINGS: Mass treatment of children was slightly more effective in
      terms of decreasing the prevalence of clinically active trachoma (estimated by
      clinical examination) and of chlamydial infection (estimated by DNA amplification
      tests), although neither result was statistically significant. CONCLUSION: Both
      strategies appeared to be effective in reducing the prevalence of clinically
      active trachoma and infection six months after the treatment. Antibiotic
      treatment reduced the prevalence of chlamydial infection more than it did the
      level of clinically active trachoma.

PMID- 11285663
TI  - Cost-effectiveness of trachoma control measures: comparing targeted household
      treatment and mass treatment of children.
AB  - OBJECTIVE: The present study compares the cost-effectiveness of targeted
      household treatment and mass treatment of children in the most westerly part of
      Nepal. METHODS: Effectiveness was measured as the percentage point change in the
      prevalence of trachoma. Resource measures included personnel time required for
      treatment, transportation, the time that study subjects had to wait to receive
      treatment, and the quantity of azithromycin used. The costs of the programme were
      calculated from the perspectives of the public health programme sponsor, the
      study subjects, and the society as a whole. FINDINGS: Previous studies have
      indicated no statistically significant differences in effectiveness, and the
      present work showed no significant differences in total personnel and
      transportation costs per child aged 1-10 years, the total time that adults spent
      waiting, or the quantity of azithromycin per child. However, the mass treatment
      of children was slightly more effective and used less of each resource per child
      aged 1-10 years than the targeted treatment of households. CONCLUSION: From all
      perspectives, the mass treatment of children is at least as effective and no more
      expensive than targeted household treatment, notwithstanding the absence of
      statistically significant differences. Less expensive targeting methods are
      required in order to make targeted household treatment more cost-effective.

PMID- 11285664
TI  - HIV/AIDS and blindness.
AB  - Nearly 34 million people are currently living with HIV/AIDS: ocular complications
      are common, affecting 50% to 75% of all such patients at some point during the
      course of their illness. Cytomegalovirus retinitis is by far the most frequent
      cause of vision loss in patients with AIDS. Although the prevalence of
      cytomegalovirus retinitis is decreasing in industrialized countries because of
      the widespread availability of highly active antiretroviral therapy, between 10%
      and 20% of HIV-infected patients worldwide can be expected to lose vision in one
      or both eyes as a result of ocular cytomegalovirus infection. Less frequent but
      important causes of bilateral vision loss in patients with HIV/AIDS include
      varicella zoster virus and herpes simplex virus retinitis, HIV-related ischaemic
      microvasculopathy, ocular syphilis, ocular tuberculosis, cryptococcal meningitis,
      and ocular toxic or allergic drug reactions. At present, most patients with
      HIV/AIDS in developing countries who lose their vision have a very limited life
      expectancy. As antiretroviral therapy makes its way to these countries, however,
      both life expectancy and the prevalence of blindness related to HIV/AIDS can be
      expected to increase dramatically.

PMID- 11285665
TI  - Corneal blindness: a global perspective.
AB  - Diseases affecting the cornea are a major cause of blindness worldwide, second
      only to cataract in overall importance. The epidemiology of corneal blindness is
      complicated and encompasses a wide variety of infectious and inflammatory eye
      diseses that cause corneal scarring, which ultimately leads to functional
      blindness. In addition, the prevalence of corneal disease varies from country to
      country and even from one population to another. While cataract is responsible
      for nearly 20 million of the 45 million blind people in the world, the next major
      cause is trachoma which blinds 4.9 million individuals, mainly as a result of
      corneal scarring and vascularization. Ocular trauma and corneal ulceration are
      significant causes of corneal blindness that are often underreported but may be
      responsible for 1.5-2.0 million new cases of monocular blindness every year.
      Causes of childhood blindness (about 1.5 million worldwide with 5 million
      visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia
      neonatorum, and less frequently seen ocular diseases such as herpes simplex virus
      infections and vernal keratoconjunctivitis. Even though the control of
      onchocerciasis and leprosy are public health success stories, these diseases are
      still significant causes of blindness--affecting a quarter of a million
      individuals each. Traditional eye medicines have also been implicated as a major
      risk factor in the current epidemic of corneal ulceration in developing
      countries. Because of the difficulty of treating corneal blindness once it has
      occurred, public health prevention programmes are the most cost-effective means
      of decreasing the global burden of corneal blindness.

PMID- 11285666
TI  - Blindness prevention programmes: past, present, and future.
AB  - Blindness and visual impairment have far-reaching implications for society, the
      more so when it is realized that 80% of visual disability is avoidable. The
      marked increase in the size of the elderly population, with their greater
      propensity for visually disabling conditions, presents a further challenge in
      this respect. However, if available knowledge and skills were made accessible to
      those communities in greatest need, much of this needless blindness could be
      alleviated. Since its inception over 50 years ago, and beginning with trachoma
      control, WHO has spearheaded efforts to assist Member States to meet the
      challenge of needless blindness. Since the establishment of the WHO Programme for
      the Prevention of Blindness in 1978, vast strides have been made through various
      forms of technical support to establish national prevention of blindness
      programmes. A more recent initiative, "The Global Initiative for the Elimination
      of Avoidable Blindness" (referred to as "VISION 2020--The Right to Sight"),
      launched in 1999, is a collaborative effort between WHO and a number of
      international nongovernmental organizations and other interested partners. This
      effort is poised to take the steps necessary to achieve the goal of eliminating
      avoidable blindness worldwide by the year 2020.

PMID- 11285667
TI  - Childhood blindness in the context of VISION 2020--the right to sight.
AB  - The major causes of blindness in children vary widely from region to region,
      being largely determined by socioeconomic development, and the availability of
      primary health care and eye care services. In high-income countries, lesions of
      the optic nerve and higher visual pathways predominate as the cause of blindness,
      while corneal scarring from measles, vitamin A deficiency, the use of harmful
      traditional eye remedies, and ophthalmia neonatorum are the major causes in low
      income countries. Retinopathy of prematurity is an important cause in middle
      income countries. Other significant causes in all countries are cataract,
      congenital abnormalities, and hereditary retinal dystrophies. It is estimated
      that, in almost half of the children who are blind today, the underlying cause
      could have been prevented, or the eye condition treated to preserve vision or
      restore sight. The control of blindness in children is a priority within the
      World Health Organization's VISION 2020 programme. Strategies need to be region
      specific, based on activities to prevent blindness in the community--through
      measles immunization, health education, and control of vitamin A deficiency--and
      the provision of tertiary-level eye care facilities for conditions that require
      specialist management.

PMID- 11285668
TI  - The SAFE strategy for the elimination of trachoma by 2020: will it work?
AB  - WHO has recently launched a programme (GET 2020) for the elimination of trachoma,
      the leading cause of preventable blindness. GET 2020 has adopted the SAFE
      strategy, a comprehensive set of control measures (Surgery for
      entropion/trichiasis; Antibiotics for infectious trachoma; Facial cleanliness to
      reduce transmission; Environmental improvements such as control of disease
      spreading flies and access to clean water). The present article reviews the
      strengths and weaknesses of each component of the strategy. Although significant
      hurdles remain to be overcome there is every reason to hope that GET 2020 will be
      successful.

PMID- 11285669
TI  - Refractive error blindness.
AB  - Recent data suggest that a large number of people are blind in different parts of
      the world due to high refractive error because they are not using appropriate
      refractive correction. Refractive error as a cause of blindness has been
      recognized only recently with the increasing use of presenting visual acuity for
      defining blindness. In addition to blindness due to naturally occurring high
      refractive error, inadequate refractive correction of aphakia after cataract
      surgery is also a significant cause of blindness in developing countries.
      Blindness due to refractive error in any population suggests that eye care
      services in general in that population are inadequate since treatment of
      refractive error is perhaps the simplest and most effective form of eye care.
      Strategies such as vision screening programmes need to be implemented on a large
      scale to detect individuals suffering from refractive error blindness. Sufficient
      numbers of personnel to perform reasonable quality refraction need to be trained
      in developing countries. Also adequate infrastructure has to be developed in
      underserved areas of the world to facilitate the logistics of providing
      affordable reasonable-quality spectacles to individuals suffering from refractive
      error blindness. Long-term success in reducing refractive error blindness
      worldwide will require attention to these issues within the context of
      comprehensive approaches to reduce all causes of avoidable blindness.

PMID- 11285670
TI  - Prevention of blindness and priorities for the future.
AB  - The impact of visual loss has profound implications for the person affected and
      society as a whole. The majority of blind people live in developing countries,
      and generally, their blindness could have been avoided or cured. Given the
      current predictions that the number of blind people worldwide will roughly double
      by the year 2020, it is clear that there is no room for complacency. As the
      world's population increases and as a greater proportion survives into late
      adulthood, so the number of people with visual loss will inexorably rise. Given
      the success of programmes in combating the most common causes of blindness
      (infectious diseases and malnutrition) which generally affect the young, and the
      projected demographic shift, age-related eye disease will become increasingly
      prevalent. Effective preventive measures for these diseases can only be
      established as more is known about their etiology. As the longevity of the
      world's population increases, the visual requirements at the workplace are also
      changing. People with low vision may be at a disadvantage in many common
      activities, and may face unemployment--particularly in technological societies.
      The definition of blindness needs to be rethought, to ensure that people with
      "economic" blindness are not forgotten. Efforts should be made to recognize and
      treat those affected at an early stage, for the benefit of the individual and
      society.

PMID- 11285671
TI  - Cataract blindness--challenges for the 21st century.
AB  - Cataract prevalence increases with age. As the world's population ages, cataract
      induced visual dysfunction and blindness is on the increase. This is a
      significant global problem. The challenges are to prevent or delay cataract
      formation, and treat that which does occur. Genetic and environmental factors
      contribute to cataract formation. However, reducing ocular exposure to UV-B
      radiation and stopping smoking are the only interventions that can reduce factors
      that affect the risk of cataract. The cure for cataract is surgery, but this is
      not equally available to all, and the surgery which is available does not produce
      equal outcomes. Readily available surgical services capable of delivering good
      vision rehabilitation must be acceptable and accessible to all in need, no matter
      what their circumstances. To establish and sustain these services requires
      comprehensive strategies that go beyond a narrow focus on surgical technique.
      There must be changes in government priorities, population education, and an
      integrated approach to surgical and management training. This approach must
      include supply of start-up capital equipment, establishment of surgical audit,
      resupply of consumables, and cost-recovery mechanisms. Considerable innovation is
      required. Nowhere is this more evident than in the pursuit of secure funding for
      ongoing services.

PMID- 11285672
TI  - Cataract blindness--the African perspective.

PMID- 11285673
TI  - Cataract genetics.

PMID- 11285674
TI  - Cataract blindness--the Indian experience.

PMID- 11285675
TI  - Can cataracts be prevented?

PMID- 11285676
TI  - Is Crede's prophylaxis for ophthalmia neonatorum still valid?

PMID- 11285677
TI  - Role of the Red Cross movement in Uganda's Ebola outbreak.

PMID- 11285678
TI  - Applying DALYs to the burden of infectious diseases.

PMID- 11285679
TI  - Even an HIV vaccine may not mean the end of AIDS.

PMID- 11285680
TI  - Restoring sight to the millions--the Aravind way.

PMID- 11285681
TI  - Inulin: a review of nutritional and health implications.

PMID- 11285682
TI  - Oriental noodles.
AB  - Oriental noodles have been consumed for thousands of years and remain an
      important part in the diet of many Asians. There is a wide variety of noodles in
      Asia with many local variations as result of differences in culture, climate,
      region and a host of other factors. In this article noodle classification,
      formulation, processing and evaluation are reviewed, with emphasis on eight major
      types. Wheat quality requirements, basic flour specifications, ingredient
      functions, and production variables are identified for different noodles. In the
      evaluation of flour for noodle making, three key quality attributes are
      considered: processability, noodle color and texture. Noodle process behavior is
      particularly important in the modern industrial production. Each noodle type has
      its own unique color and texture characteristics. Flour color, protein content,
      ash content, yellow pigment and polyphenol oxidase activity are important factors
      responsible for noodle color. Starch characteristics, protein content and quality
      play major roles in governing the texture of cooked noodles. However, the
      relative importance of starch and proteins varies considerably with noodle type.
      Starch pasting quality is the primary trait determining the eating quality of
      Japanese and Korean noodles that are characterized by soft and elastic texture,
      while protein quantity and strength are very important to Chinese-type noodles
      that require firm bite and chewy texture. Other factors such as ingredients added
      in the noodle formula and processing variables used during noodle preparation
      also affect the cooked noodle texture as well.

PMID- 11285683
TI  - The role of natural color additives in food allergy.
AB  - A critical evaluation of the available information demonstrates that reactions to
      natural color additives are rare. Studies of turmeric and carotenoid pigments
      administered in mixtures with other food colorings failed to definitely identify
      reactions to either color additive. For carotenoids, the one case report of an
      adverse reaction was not conclusive. An anaphylactic reaction to saffron does
      suggest an IgE-mediated reaction, but the high use of saffron as compared with
      this single report of an adverse reaction suggests that sensitivity to saffron is
      extremely rare. Numerous reports of reactions to grapes or grape products have
      been reported in the literature, but no reports of sensitivities to grape skin
      extract or grape color extract were found. In rare cases, annatto dye may provoke
      a severe, adverse reaction in individuals with an uncommon hypersensitivity, and
      may aggravate the symptoms of patients suffering from recurrent urticaria. In its
      long history of use, there has been only one reported case of anaphylaxis
      resulting from the ingestion of annatto. Studies designed to investigate the role
      of annatto in recurrent urticaria sufferers were limited due to the absence of
      double-blind challenge and placebo controls. A number of cases of adverse
      reactions to carmine following ingestion have been reported in the literature.
      These adverse reactions suggest an IgE-mediated hypersensitivity. In many of the
      reported cases, the cause of sensitization to carmine was topical exposure from
      the use of carmine-containing cosmetics or occupational exposure to carmine and
      not from ingestion of carmine-containing foods and beverages. Following
      sensitization, affected individuals would be sensitive to carmine and the amounts
      present in foods and beverages could elicit allergic reactions. It is not known
      whether all individuals with carmine sensitivity induced through topical use are
      sensitive to the ingestion of carmine in foods. However, reactions to carmine
      solely because of ingestion are likely to be exceedingly rare due to the low use
      levels of carmine in foods and beverages. Despite their widespread use in food
      products, few reports of allergic reactions following ingestion have been
      reported for the majority of natural color additives. It is concluded that the
      ingestion of natural color additives presents a very low risk of provoking
      adverse reactions.

PMID- 11285684
TI  - Developments in sorghum food technologies.

PMID- 11285685
TI  - Bovine spongiform encephalopathy--food safety implications.

PMID- 11285686
TI  - Microbial attachment to food and food contact surfaces.

PMID- 11285687
TI  - Microwave technology and foods.

PMID- 11285688
TI  - Adolescent risk-taking behavior: a review of the role of parental involvement.

PMID- 11285689
TI  - [Living donors in kidney and liver transplantation].
AB  - The shortage of organs available for transplantation has rekindled the interest
      for the kidney living donor, and has recently induced the use of living donors
      for liver transplantation too. Both methods raise many medical and ethical
      interrogations. The aim of this paper is to analyse this type of organ
      harvesting, and to report our experience and results with kidney and liver living
      donors.

PMID- 11285690
TI  - [Gene therapy and cancer].
AB  - Gene therapy by definition aims at modifying the genetic program of a cell
      towards a therapeutic or prophylactic goal. Several gene therapy strategies for
      cancer are currently under evaluation: 1) "suicide" gene therapy where an
      inactive prodrug is converted into a cytotoxic drug; 2) modification of the
      function of oncogenes and tumor suppressor genes; 3) modification of the host
      immune response towards the tumor; 4) disruption of the tumor neovascularisation;
      5) lysis of tumor cells with replication-competent viruses. Recent results of
      phase I and II clinical studies have brought great hopes. However, the
      inefficiency of current gene vectors in infecting targeted cells and their
      inability to selectively access diseased cells distributed systemically are two
      major limitations that have to be overcome for further successful clinical
      applications.

PMID- 11285691
TI  - [Surgical treatment of hepatic metastases].
AB  - The liver is a common site for metastases from various forms of primary tumors.
      Colorectal cancer most commonly, but also neuroendocrine tumors, gastrointestinal
      sarcoma, ocular melanoma and others metastasize to the liver. A complete staging
      is important before considering treatment options. Surgical resection is the only
      form of curative treatment for colorectal cancer metastases. Systemic or
      intraarterial hepatic chemotherapy may be an alternative for patients with
      unresectable disease. Other promising treatment options such as cryotherapy and
      radiofrequency ablation are curRently under evaluation. The treatment of
      metastases from neuroendocrine tumors and other noncolorectal primary
      malignancies has to be individualized based on the patient's clinical status and
      the extent of the disease.

PMID- 11285692
TI  - [Surgical site infection surveillance: an effective preventive measure].
AB  - Surgical site infection (SSI) is a feared complication of any surgical procedure.
      Despite clear progresses during the last decades, recent studies (some from
      Switzerland) show that many patients still suffer from SSIs and that SSIs have a
      huge impact for patients and public health. Thus, the prevention of SSIs must
      constitute a priority of nosocomial infections control in hospitals. In addition
      to classical approaches focusing on skin preparation, antibiotic prophylaxis,
      asepsis, and operative environment, surveillance has proved effective in
      decreasing the incidence of SSIs. The present paper reviews the principles and
      the main components of an SSI surveillance program.

PMID- 11285693
TI  - [Advanced Trauma Life Support: towards a standardization of care for the trauma
      patient].
AB  - The ATLS concept is a strategy for the treatment of the injured patient and a
      teaching method. ATLS originates from the USA and it was introduced in the French
      speaking part of Switzerland two years ago. This article describes the principles
      that made ATLS successful, as well as its objectives and impact on the treatment
      of injured patients. As a consequence, a trend is now emerging towards a
      standardisation of care of the trauma patient.

PMID- 11285694
TI  - [Validation of laparoscopic surgical techniques].
AB  - The use of laparoscopic surgery has increased rapidly. However, a technically
      feasible procedure is not automatically recommendable. Thus, if cholecystectomy
      and fundoplication are currently fully validated techniques, this does not hold
      true for gastroplasty and kidney harvesting for transplantation: these operations
      are feasible indeed but their efficacy remains to be proved. Laparoscopic
      oncology has been shown to be feasible too, but its efficacy has not been
      documented yet.

PMID- 11285695
TI  - [Revascularization of the diabetic foot].
AB  - Diabetes is an important risk factor for atherosclerosis. The diabetic foot is
      characterised by the association of arteriopathy and neuropathy. The vascular
      damage associates a non-occlusive microangiopathy and a macroangiopathy. The
      first principles of treatment are the control of pain, of an eventual infection,
      and the restoration of pulsatile blood flow in case of ischemia. Angiologic
      investigation must be undertaken, as well as an arteriography, in order to plan
      the revascularisation. The treatment options are angioplasty with or without
      stenting and surgery. Distal reconstructions with anastomosis to the leg or pedal
      arteries have a satisfactory limb-salvage rates. This aggressive and systematic
      approach to the diabetic foot is economically sound, allows hope for limb salvage
      and improves the quality of life.

PMID- 11285696
TI  - [Value of the "sleeve" resection for pulmonary cancers].
AB  - A sleeve resection is an anatomical pulmonary resection (segmentectomy, lobectomy
      or pneumonectomy) combined with the excision of a bronchial segment, with the
      anastomosis between the airway proximal and distal to it. This technique allows a
      certain number of centrally located tumors to be completely resected with
      sufficient margins of healthy tissue. Thus it is possible that the rest of the
      involved lung can be spared (sleeve segmentectomy or lobectomy), or a
      pneumonectomy can be performed despite invasion of the carina or distal trachea.
      The comparison of series of sleeve and conventional resections shows similar 5
      year survival rates if the stage and histological subtypes are taken into
      account. The specific morbidity of the procedure is the partial or complete
      breakdown of the anastomosis (producing a stenosis or a bronchopleural fistula).
      This is uncommon and can usually be prevented by the use of a protective
      perianastomotic flap.

PMID- 11285697
TI  - [Psychiatric disorders in elderly patients with Parkinson's disease and their
      treatments].
AB  - Parkinson's disease (PD) is a neuropsychiatric disorder. During the course of PD,
      most patients develop at least one psychiatric syndrome. Depression is the most
      frequent disorder and affects nearly half of all patients. The use of an
      increasing number of new drugs, in particular the dopaminergic agents, puts these
      patients at risk of developing both delirium and psychosis. This article
      summarizes the different psychiatric syndromes seen in PD and gives an account of
      the various treatment possibilities.

PMID- 11285699
TI  - [Euthanasia: ethical questions. Opening message].

PMID- 11285698
TI  - [Giardia lamblia gastritis. A case report].
AB  - A 56 year-old male patient had a gastric resection (Billroth II) at age 33. In
      1993 he had vague upper digestive complaints. During investigations for a
      moderate anaemia biopsies performed during an oesogastroduodenoscopy revealed a
      jejunitis with Giardia lamblia (G.l.) trophozoites which were also found on the
      gastric mucosa associated with Helicobacter pylori related chronic active
      gastritis. The few publications dealing with the presence of Giardia lamblia in
      the stomach either assert or cast some doubts on the pathogenicity of this
      protozoa for the gastric mucosa. Gastric involvement by G.l. is usually
      associated with duodeno-jejunal disease responsible for diarrhoea which may occur
      as epidemics of varying extension. Since Giardia lamblia infection is not
      submitted to reporting in Switzerland, the epidemiology in our country is
      scarcely known and investigated. In our opinion, however, health authorities in
      Switzerland should consider the need of reporting this infectious disease.

PMID- 11285700
TI  - [Some religious and ethical aspects of active, direct euthanasia].

PMID- 11285701
TI  - [Euthanasia, view of a clinician].

PMID- 11285702
TI  - [Point of view on assisted suicide].

PMID- 11285703
TI  - [Point of view. Who is crazy?].

PMID- 11285705
TI  - [Transplantation medicine: a social debate].
AB  - Twenty-eight randomly chosen citizens originating from the three linguistic areas
      of Switzerland discussed transplantation medicine in November 2000. This
      PubliForum was organised by the Swiss Federal Office of Public Health, the Swiss
      National Science Foundation and the Swiss Centre for Technology Assessment. The
      aim was to explore the hopes, fears and emotions raised in the population by this
      highly sophisticated therapy. After a 2-day hearing of specialists and concerned
      persons, the citizens wrote a report dealing with the definition of death, the
      consent for organ harvesting, the criteria for the allocation of donated organs
      and xenotransplantation research. The panel made a plea for a thorough public
      debate on these topics. They also stressed that information and transparency are
      key issues to guarantee that the social and individual needs of the donors, the
      recipients and their involved relatives will be met.

PMID- 11285706
TI  - [Twelve years of liver transplantation in Lausanne].
AB  - From 1988 to June 2000 138 transplantations were performed in 129 adult patients.
      Actuarial patient and graft survivals have been 80.7% and 75.4% at one year and
      67.8% and 63.5% at 10 years. This compares favourably with the statistics of the
      European Liver Transplant Registry that collected data from more than 30,000
      grafts. Over the twelve years of activity, the indications have become more
      liberal and the techniques have been simplified. The waiting list has therefore
      grown and some patients are now unfortunately dying before a graft can be found
      because the number of brain dead donors remains stable. In order to palliate this
      shortage, older donors are now being accepted even with co-morbidities and/or
      moderate alterations of the liver function tests. The use of live donors and the
      split of the best cadaveric grafts for two recipients will also reduce the gap
      between the demand and the offer.

PMID- 11285707
TI  - [Joint radiography in patients with gonarthrosis].

PMID- 11285708
TI  - [Preclinical development of a medication: application to diacerhein].

PMID- 11285709
TI  - [Physical exercise and arthrosis].

PMID- 11285710
TI  - [Biomechanical bases of surgical treatment of arthrosis].

PMID- 11285711
TI  - [Orthoses, soles, and functional reeducation: are there solutions to the
      biomechanical problems of lower limb arthrosis?].

PMID- 11285712
TI  - [Measurement of the radiologic articular interlinear narrowing space in
      coxarthrosis. Practical value for the study of the natural course of the disease
      and help for therapeutic decision making].

PMID- 11285713
TI  - [Epidemiology of arthrosis].

PMID- 11285714
TI  - [Role of mechanical constraints in the maintenance and degradation of articular
      cartilage].

PMID- 11285715
TI  - Are guidelines achievable today and in the future? Proceedings of a Satellite
      Symposium held at the 71st European Atherosclerosis Society Congress, Athens,
      Greece, 28 May 1999.

PMID- 11285716
TI  - The benefit of aggressive lipid lowering.
AB  - The beneficial effects of lipid-lowering therapy for the primary and secondary
      prevention of coronary heart disease (CHD) have been conclusively demonstrated in
      large-scale clinical trials. Does more aggressive lipid lowering provide even
      greater clinical benefit? The post coronary artery bypass graft (post-CABG) study
      was the first angiographic trial to show that aggressive lipid-lowering therapy
      was more effective at reducing disease progression than conventional approaches
      to cholesterol management. Recently, the results of the atorvastatin versus
      revascularization treatments (AVERT) trial have also shown significant benefit on
      clinical events with aggressive lipid lowering. A total of 341 patients with
      stable CHD were randomly assigned to receive medical therapy with atorvastatin 80
      mg/day plus conventional treatment or angioplasty followed by usual care.
      Atorvastatin therapy resulted in a 46% reduction in the mean low-density
      lipoprotein cholesterol level compared with an 18% decrease for patients in the
      angioplasty/usual care group. Patients treated with atorvastatin had fewer
      ischemic events compared with those who had angioplasty (13 vs. 21%, P = 0.048)
      and a significantly greater time to first ischemic event (P = 0.027). AVERT is
      the first clinical study demonstrating that patients with stable CHD achieve
      significant cardiovascular benefit by aggressively lowering cholesterol levels
      with atorvastatin. It would therefore appear that an aggressive approach to lipid
      lowering therapy is beneficial in patients with existing CHD.

PMID- 11285717
TI  - Treating to target with statins.
AB  - Large-scale drug intervention trials have proven that cholesterol-lowering
      therapy reduces the risk of coronary events in a wide range of at-risk patient
      groups. This has led to a growing consensus that plasma total and low-density
      lipoprotein cholesterol (LDL-C) should be reduced to target levels that have been
      shown in population studies to be associated with low rates of coronary heart
      disease (CHD). Despite this consensus, however, a substantial proportion of
      patients at high coronary risk still do not receive lipid-lowering therapy.
      Furthermore, of those patients receiving therapy, many do not achieve the
      recommended targets. In order to address this problem, several treatment-to
      target studies have been conducted to determine whether recommended targets are
      attainable with the lipid-lowering drugs that are currently available. These
      studies have confirmed that the statins are able to achieve recommended target
      levels in the majority of patients at risk. The studies have also demonstrated
      that most patients achieve a total cholesterol target with atorvastatin.

PMID- 11285718
TI  - The revised joint guidelines.
AB  - There is a wealth of scientific evidence that lifestyle interventions and the use
      of drug therapies in patients with coronary heart disease (CHD) and individuals
      at high risk for developing CHD can reduce cardiovascular morbidity and
      mortality. In the revised guidelines of the European Joint Task Force for the
      prevention of CHD in clinical practice, these individuals remain the priority for
      prevention. The new guidelines have been formulated as a result of evidence from
      numerous epidemiological, observational and clinical trials and define specific
      goals of therapy for the management of lipids, blood pressure and diabetes. The
      intensity of lifestyle intervention and need for drug therapy should be
      determined by the absolute risk of a major ischemic event, based on an assessment
      of all risk factors. Implementation of these recommendations in clinical practice
      will ensure a common approach to CHD prevention throughout Europe and improve
      patients' quality of life.

PMID- 11285719
TI  - Are we treating to target?
AB  - The identification of a number of independent risk factors for coronary heart
      disease (CHD) led to the development of guidelines for the prevention of CHD in
      an attempt to target these risk factors and reduce the rates of CHD-related
      morbidity and mortality. Surveys conducted of physician's clinical practice
      patterns indicate, however, that the recommendations made in the guidelines are
      often not implemented and the predefined goals of therapy for patients are not
      achieved. Possible reasons for this apparent shortfall in preventive care include
      a lack of physician awareness of evidenced-based guidelines, an insufficient
      focus towards preventive care in health care systems, and patient non-compliance
      with lifestyle changes and medication. To ensure an optimal outcome, specialists,
      primary care physicians and the patient need to provide an integrated approach to
      the management of CHD. The first step is to achieve universal understanding and
      implementation of the guidelines. Not only do guidelines promote interventions of
      proven benefit, but when followed they also improve consistency of care. Nurse
      led shared-care programs, which individualize care based on a comprehensive
      assessment of CHD risk factors, are of proven benefit and offer continuity
      between the hospital and a patients return to the community. Patients themselves
      also have a role to play in the management of their disease by adhering to
      lifestyle changes and medication.

PMID- 11285720
TI  - Field observations on the variability of crude oil impact on indigenous
      hydrocarbon-degrading bacteria from sub-Antarctic intertidal sediments.
AB  - Oil pollution of the oceans has been a problem ever since man began to use fossil
      fuels. Biodegradation by naturally occurring populations of micro-organisms is a
      major mechanism for the removal of petroleum from the environment. To examine the
      effects of crude oil pollution on intertidal bacteria, we repeated the same
      contamination experiments on nine different sub-Antarctic intertidal beaches
      using specifically built enclosures (PVC pipe, 15 cm in inner diameter and 30 cm
      in height). Despite the pristine environmental conditions, significant numbers of
      indigenous hydrocarbon-degrading bacteria were observed in all the studied
      beaches. Introduction of oil into these previously oil-free environments resulted
      in several orders of magnitude of increase in hydrocarbon-degrading micro
      organisms within a few days in some of the studied sites but has no obvious
      effects on two others. The physical environment of the bacterial assemblage seems
      to play a major role in the biodegradation capacities. After 3 months of
      contamination, both remaining oil concentrations and biodegradation indexes
      differ strongly between the different stations. Thus, chemical and biological
      parameters reveal a strong heterogeneity of biodegradation capacities between the
      different sites.

PMID- 11285721
TI  - Trophic accumulation and depuration of mercury by blue crabs (Callinectes
      sapidus) and pink shrimp (Penaeus duorarum).
AB  - Mercury concentrations in blue crabs (Callinectes sapidus) collected from an area
      of mercury-contaminated sediments in Lavaca Bay, TX, USA, are more than an order
      of magnitude greater than concentrations in penaeid shrimp from the same area.
      Laboratory feeding experiments using mercury-contaminated fish as food showed
      that both blue crabs and pink shrimp (Penaeus duorarum) could accumulate mercury
      concentrations comparable to those in their food in 28 days. Calculated mercury
      assimilation efficiencies averaged 76% for blue crabs and 72% for pink shrimp.
      Significant depuration of mercury by blue crabs was not observed during a
      subsequent 28-day period, but pink shrimp lost mercury at a rate of about 0.012
      day-1. Model calculations predict biomagnification factors of mercury of about
      two to three at steady state for both species. The large difference in observed
      concentrations of mercury in field-collected blue crabs and penaeid shrimp does
      not result from differences in efficiency of mercury assimilation from their food
      or from differences in excretion rates. It is more likely the result of
      differences in residence times in the contaminated area and of differences in
      feeding habits.

PMID- 11285722
TI  - Imposex in the rock shell, Thais clavigera, as evidence of organotin
      contamination in the marine environment of Korea.
AB  - Imposex was measured in the rock shell, Thais clavigera, from the coast of the
      Korean peninsula. Frequency of imposex was 0% at two reference sites, but at 47
      out of 61 sites, frequency of imposex was recorded as 100%. The degree of imposex
      was relatively high at the sites near a harbor and a shipyard. Tributyltin (TBT)
      and triphenyltin (TPT) concentrations in T. clavigera ranged from 5 to 508 ng/g
      and from 3 to 2460 ng/g, respectively. A significant positive relationship was
      found between degree of imposex and organotin concentration, whereas a
      significant negative relationship was obtained between female-to-male sex ratio
      and the degree of imposex. During a field transplantation of T. clavigera from a
      pristine area to a port, TBT and TPT were accumulated in T. clavigera, and
      imposex was induced. T. clavigera shows considerable potential as a bioindicator
      species of the adverse effects of TBT and TPT contamination.

PMID- 11285723
TI  - Plasma steroid levels in female flounder (Platichthys flesus) after chronic
      dietary exposure to single polycyclic aromatic hydrocarbons.
AB  - The chronic effects of polycyclic aromatic hydrocarbons (PAHs) on ovary
      development, total hepatic lipids and plasma sex- and corticosteroid levels in
      female flounder (Platichthys flesus) were examined. Sexually mature feral female
      flounder were exposed via the diet to phenanthrene (0.5, 2.5 or 12.5 nmol/g food)
      or chrysene (0.4 nmol/g food) for 12 weeks, during the previtellogenic phase of
      the annual reproductive cycle. PAH exposure did not directly affect germ cell
      development since no structural and/or developmental differences were observed
      between control and exposed fish. On the contrary, all treatments resulted in
      altered plasma steroid levels. The most pronounced effect was the significant
      decrease in plasma 17 beta-estradiol to 19 +/- 11%, 27 +/- 7%, 63 +/- 20% and 61
      +/- 12% in relation to control fish, respectively, in flounders exposed to 12.5,
      2.5 or 0.5 nmol phenanthrene/g food and 0.4 nmol chrysene/g food. Impaired
      ovarian growth was not observed, most likely because experiments were ended
      before the period of vitellogenesis, even though a non-significant general
      decline in total hepatic lipids could be observed. Moreover, all exposed
      flounders, except fish fed with the highest amount of phenanthrene, showed a
      negative correlation between plasma 17 beta-estradiol and 17 alpha
      hydroxyprogesterone levels (r = -0.46). One possible explanation is that PAH
      action may be mediated by a specific inhibition of steroidogenic enzymes. These
      findings provide evidence that selected PAHs are antiestrogenic xenobiotics with
      the capability to impair female teleost reproductive function.

PMID- 11285724
TI  - Acoustic interaction of humpback whales and whale-watching boats.
AB  - The underwater acoustic noise of five representative whale-watching boats used in
      the waters of west Maui was measured in order to study the effects of boat noise
      on humpback whales. The first set of measurements were performed on 9 and 10
      March, close to the peak of the whale season. The ambient noise was relatively
      high with the major contribution from many chorusing humpback whales.
      Measurements of boat sounds were contaminated by this high ambient background
      noise. A second set of measurements was performed on 28 and 29 April, towards the
      end of the humpback whale season. In both sets of measurements, two of the boats
      were inflatables with outboard engines, two were larger coastal boats with twin
      inboard diesel engines and the fifth was a small water plane area twin hull
      (SWATH) ship with inter-island cruise capabilities. The inflatable boats with
      outboard engines produced very complex sounds with many bands of tonal-like
      components. The boats with inboard engines produced less intense sounds with
      fewer tonal bands. One-third octave band measurements of ambient noise measured
      on 9 March indicated a maximum sound pressure level of about 123 dB re 1 microPa
      at 315 Hz. The maximum sound pressure level of 127 dB at 315 Hz was measured for
      the SWATH ship. One of the boats with outboard engines produced sounds between 2
      and 4 kHz that were about 8-10 dB greater than the level of background humpback
      whale sounds at the peak of the whale season. We concluded that it is unlikely
      that the levels of sounds produced by the boats in our study would have any grave
      effects on the auditory system of humpback whales.

PMID- 11285725
TI  - Networking and expert-system analysis: next frontier in biomonitoring.
AB  - The extensive use of biomarkers in environment biomonitoring programmes has
      raised the problem of data management and intercomparison. A research project
      (Pollution Effect Network, PEN) is proposed here, consisting of the realisation
      of an on-line warehouse for biomarker data (http://www.muf.unipmn.it/pen). The
      web site will contain repository sections and expert system procedures able to
      integrate information from different biomarkers and provide ranking of the
      organism health status in terms of synthetic stress syndrome indexes. Researchers
      accessing the site will be able to submit and process their own data. This will
      allow common criteria in the evaluation of the biological effects of pollutants,
      and an intercomparison of biomonitoring data among different geographic areas and
      sentinel species.

PMID- 11285726
TI  - Correlation between the level of the potential biomarker, heat-shock protein, and
      the occurrence of DNA damage in the dab, Limanda limanda: a field study in the
      North Sea and the English Channel.
AB  - In the present study, heat-shock protein of M(r) 70 kDa (HSP70), a marker of
      cellular stress response, was validated as a potential biomarker under field
      conditions. The dab, Limanda limanda (female, size > or = 25 cm, spawning
      maturity stage 2) was used as the indicator organism. The data on HSP level were
      correlated with the occurrence of DNA damage, measured in the same specimens of
      L. limanda, to prove the usefulness of the method. The area under investigation
      was the North Sea. Four locations were selected: station N01, close to
      Heligoland, in the North Sea; station N04 at the Dogger Bank; station N06 at the
      Firth of Forth; and station G08 in the English Channel. Ten animals from each
      location were selected and their livers used for the experiments. The results
      show that the highest levels of HSP70 (consisting of two forms of M(r) 75 and 73
      kDa) were in fish from station N04, while low values were measured in livers from
      L. limanda collected at station N01. Intermediate levels were seen in the animals
      from the two other locations. By application of a novel technique, it was found
      that the extent of DNA damage (single-strand breaks and alkaline labile sites) in
      fish liver parallels the levels of both HSP70 forms. Our results suggest that L.
      limanda may be a useful bioindicator and heat-shock proteins, a useful biomarker
      for monitoring of environmental pollution.

PMID- 11285727
TI  - Interactions between dissolved petroleum hydrocarbons and pure and humic acid
      coated mineral surfaces in artificial seawater.
AB  - The adsorption of total petroleum hydrocarbons (TPHs) on suspended particles in
      the marine environment is an important process affecting the fate of oils spilled
      in the ocean. Adsorption kinetics and adsorption isotherms of the water-soluble
      fraction of Fuel Oil No. 6 were performed on pure and humic acid-modified
      montmorillonite, alumina and kaolinite. The rates of adsorption on all sorbents
      are very fast and a pseudo-equilibrium is reached within 0.5 h. Linear adsorption
      isotherms were obtained for TPH and individual aromatic hydrocarbons on all
      sorbents. Higher sorption coefficients (Kd) were obtained for the humic acid
      coated clays compared to the pure clays. However, a great contribution of mineral
      surface to overall adsorption was found on humic acid-modified particles in this
      study. A linear relationship between the log K and log Kow was also found for
      individual compounds on both pure alumina (log Km) and humic acid-coated alumina
      (log Koc).

PMID- 11285728
TI  - Long-term recovery of a Louisiana brackish marsh plant community from oil-spill
      impact: vegetation response and mitigating effects of marsh surface elevation.
AB  - Oil spills can have significant, short-term, negative impacts on coastal marshes,
      but the long-term effects and eventual recovery are not well documented,
      particularly in brackish marshes. The goals of this investigation were to: (1)
      document the long-term recovery of a Louisiana brackish marsh plant community
      impacted by a 1985 oil spill; (2) separate the effect of the oil spill on marsh
      deterioration from ambient rates of marsh deterioration; and (3) assess the
      relative importance of residual oil in the sediment and decreased marsh surface
      elevation in the failure of certain areas to recover. A total of 68 permanent
      plots previously established in 1985 were re-surveyed for plant and soil recovery
      in the fall of 1989. Although substantial (and near total) vegetative recovery
      was evident by significant increases in live and total vegetative cover, many of
      the plots that were initially heavily impacted by oil still displayed elevated
      levels of total saturated hydrocarbons in the soil. August 1990 measurements of
      plant photosynthetic response and edaphic variables revealed no significant
      differences between control plots and plots heavily impacted by oil that
      displayed vegetative regrowth. Rates of wetland land loss in the oiled marsh
      during an 8-year period that bracketed the time of the spill were within the
      historical range measured for this site and similar to the land loss rates of
      adjacent reference marshes. Results from a manipulative field transplant
      experiment indicated that the long-term failure of certain small areas to
      revegetate was primarily due to a decrease of marsh surface elevation (increased
      flooding stress), not a residual oil effect.

PMID- 11285729
TI  - Does historical exposure to hydrocarbon contamination alter the response of
      benthic communities to diesel contamination?
AB  - A microcosm experiment was used to compare the influence of diesel contamination
      on two benthic salt-marsh communities, one chronically exposed to petroleum
      hydrocarbons for decades (Louisiana [LA]) and the other relatively uncontaminated
      (Mississippi [MS]). Initial meiofaunal community composition of the two sites was
      similar. Higher organic content of MS sediments should have reduced
      bioavailability, and thus the toxicity of hydrocarbons relative to the LA site.
      Nevertheless, although responses to diesel contamination at the two sites were
      generally qualitatively similar, a species-specific and several community
      response variables were influenced to a much greater degree in the MS community.
      In particular, the abundance of total nauplii, ostracods, and copepods were
      negatively impacted to a greater extent in MS than in LA, as was grazing by
      ostracods on benthic microalgae. Nematode:copepod ratios in contaminated
      sediments were much higher in MS than in LA sediments. Pseudostenhelia wellsi (a
      benthic copepod) nauplii suffered greater adverse effects of diesel in MS than in
      LA. We conclude that the MS community was more sensitive to diesel contamination
      than was the LA community. The differential sensitivity is presumably a
      manifestation of different tolerances to hydrocarbon contaminants, mediated by a
      higher proportion of more tolerant species and/or increased tolerance among
      individual species in LA. Although the MS site was more sensitive to diesel
      contamination, qualitative response of the LA and MS communities were similar,
      and comparable to previous studies of diesel contamination. The spatial and
      temporal consistency of diesel impacts on salt-marsh communities suggests that
      hydrocarbon contamination results in predictable community responses.
      Specifically, crustacean (e.g. copepods, ostracods, and nauplii) benthos are most
      sensitive to hydrocarbons. Reductions in abundance and grazing activity of
      crustaceans leads to enhanced algal biomass, reduced copepod diversity, and
      alters competitive interactions among meiofauna.

PMID- 11285730
TI  - Seasonal variation of Zn, Pb, Cu and Cd concentrations in the root-sediment
      system of Spartina maritima and Halimione portulacoides from Tagus estuary salt
      marshes.
AB  - Concentrations of Zn, Pb, Cu and Cd have been determined in leaves, stems and
      roots of Spartina maritima and Halimione portulacoides from the Tagus estuary
      salt mash (Corroios) and in the sediments between their roots. Biological
      materials and sediments were sampled every 2 months, between July 1991 and July
      1992. Root biomass increased from July to September and from January to March.
      The greatest metal concentrations occurred in the roots, with lowest levels in
      January and increasing levels during the growth periods. Zn, Pb and Cu in
      sediments exhibited a corresponding change in concentrations, reaching maximum in
      January and subsequently decreasing in spring. The ratios between metal
      concentrations in the root and in sediments were higher for H. portulacoides when
      compared to S. maritima, whose roots are surrounded by a more acidic and reduced
      sediment environment. It was concluded, therefore, that H. portulacoides is a
      more effective accumulator of metals than S. maritima, and both root-sediment
      systems exhibited a seasonal variation of metal concentrations.

PMID- 11285731
TI  - Spatial distribution of persistent organochlorines in ringed seal (Phoca hispida)
      blubber.
AB  - Blubber samples, taken through the entire blubber column, were collected from
      three different anatomical locations on ringed seals (Phoca hispida). The outer
      and inner layers of these samples were analysed for concentrations of sigma PCBs
      (sum of the analysed congeners, polychlorinated biphenyls) and p,p'-DDE (4,4'
      dichlorodiphenyldichloroethylene). No significant differences were found in
      blubber thickness or in per cent extractable lipid when comparing age- and sex
      groups, or in extractable lipid content when comparing anatomical locations of
      the blubber or blubber depth. No significant differences were found between the
      three different anatomical locations with respect to the concentrations of sigma
      PCBs or p,p'-DDE. However, the concentrations of both sigma PCB and p,p'-DDE were
      significantly higher in the outer blubber layer compared to the inner. Higher
      levels of both sigma PCB and p,p'-DDE were found in males compared to females and
      juveniles in both the inner and outer parts of the blubber column. The most
      commonly used blubber sampling devices are biopsy tools that penetrate only the
      outer layer of the blubber. Analyses of such samples will not reflect the real
      body burden of organochlorines. Standard methods for sampling blubber of marine
      mammals should be developed so that comparative studies and longitudinal
      monitoring programs of pollutants in marine mammals can be conducted in a
      meaningful way.

PMID- 11285732
TI  - Extreme variation in the concentration of trace metals in sediments and bivalves
      from the Bilbao estuary (Spain) caused by the 1989-90 drought.
AB  - Intertidal sediments and bivalves Scrobicularia plana from Bilbao estuary (Spain)
      were repeatedly sampled during and after the 1989-90 drought. The organic content
      (OC) and the concentration of most of the 10 metals analysed in sediments were
      extremely variable (e.g. Cd ranged from 4 to 112 micrograms g-1, ppm dry wt), and
      they were strongly related to an index applied to estimate the magnitude of the
      drought (namely the deficit flow of the main river). After OC normalisation, the
      correlation versus deficit was lost for some elements (Cr, Fe, Ni) but not for
      others (Cd, Co, Cu, Pb, Zn). This leads to the conclusion that both a natural and
      a man-induced process account for the observed rise and fall of the contamination
      pattern: the reduced river flow raised the metal-binding capacity of sediments,
      and restrictions in the water supply increased the corrosion of sewers and their
      leaching of some elements. The concentration of trace metals in local bivalves
      (Cd reached 100 and 458 ppm dry wt, respectively, for whole tissues and digestive
      gland) mirrored the sediment contamination dynamics, but at a slower pace. The
      means by which S. plana is able to tolerate such high Cd tissue levels remain
      unknown. These results constitute some prime field evidence of drought effects
      that should be born in mind when pollution and risk from climate change are
      assessed in estuaries.

PMID- 11285733
TI  - Recent changes of biogenic carbonate deposition in anoxic sediments of the Black
      Sea: sedimentary record and climatic implication.
AB  - Recent changes of carbonate deposition were traced in a Black Sea sediment core
      taken in the western abyssal basin. The sediments were dated from a vertical
      profile of excess 210Pb. The 210Pb geochronology corresponded well to the 137Cs
      fallout record. A 20-year cyclic variability of carbon deposition has been traced
      in the dated sediments and has been related inversely to the long-term changes in
      temperature of air over the basin, forcing the convection in the upper water
      column, which may bear influence upon the coccolithophorid blooms by bringing
      nutrients from deeper water to the surface.

PMID- 11285734
TI  - Lead in the southern East China Sea.
AB  - At present, in most oceans the lead (Pb) biogeochemical cycling has been
      disturbed by anthropogenic Pb through atmospheric input. The Pb concentrations in
      the upper water positively correlate with atmospheric input fluxes of Pb. The
      North Pacific is affected greatly by atmospheric substances via long-range
      transport from eastern Asia, especially from Mainland China. Mainland China may
      export considerable amounts of pollutants into the seas via rivers and the
      atmosphere owing to its recent fast growth in industry and economy. The East
      China Sea lies in an important geographical position--a transit between Mainland
      China and the western North Pacific. However, no data are available for seawater
      concentrations of Pb, a representative element with anthropogenic origin. In this
      work seawater samples from both 5 and 30-50 m water layers of 15 stations
      occupied over a cyclonic eddy in the southern East China Sea were analyzed for
      particulate Pb (PPb) and dissolved Pb (DPb). The Mean concentration of DPb
      (approximately 128 ng/l) in the southern East China Sea upper waters (< or = 50
      m) is approximately several times higher than those in the Pacific; the high DPb
      concentrations in the southern East China Sea waters correspond to much higher
      atmospheric supplies of Pb to the East China Sea. Thus, this study partly fills
      the 'data gap' of the marginal seas. Also, it indicates that the East China Sea
      may be considerably contaminated by deposited polluted aerosols. Spatial
      distributions of DPb in the surface water show a tendency of increasing
      concentrations with distance offshore, that depends on the magnitudes of
      atmospheric Pb inputs and on particle scavenging processes. In contrast to DPb,
      spatial distributions of PPb basically display an 'omega'-like picture and a
      tendency of decreasing concentrations with distance offshore. These are related
      to riverine and scavenging sources and to the drive by the eddy. Additionally,
      the residence times of DPb in the surface water were estimated to be about 2
      years, agreeing well with the reported data.

PMID- 11285736
TI  - Detection distances of bottom-set gillnets by harbour porpoises (Phocoena
      phocoena) and bottlenose dolphins (Tursiops truncatus).
AB  - Many odontocetes die annually in gillnet fisheries. Why they become entangled is
      not yet clear. Maybe some species detect the nets too late to avoid collision.
      Therefore, the target strength of 11 types of bottom-set gillnets was measured
      under 0 and 45 degrees angles of incidence. From these target strengths and from
      knowledge on the echolocation abilities of two odontocete species (harbour
      porpoises, bottlenose dolphins), the detection ranges of the nets by these small
      cetaceans could be estimated. The 90% detection range by echolocating harbour
      porpoises, approaching the nets at right (perpendicular) angles under low noise
      level conditions, varied between 3 and 6 m depending on the net type. For
      bottlenose dolphins, under high noise conditions, the 90% detection range varied
      between 25 and 55 m. At other angles of approach, the estimated detection ranges
      are shorter. The study suggests that echolocating bottlenose dolphins can detect
      nets in time to avoid collision, whereas echolocating harbour porpoises cannot in
      most cases. Suggestions for future research to reduce small cetacean bycatch by
      improving the nets' detectability by echolocation are given.

PMID- 11285735
TI  - Biological transport and mammal to mammal transfer of organochlorines in Arctic
      fauna.
AB  - Ringed seal (Phoca hispida) is assumed to be the most important and common prey
      of polar bears (Ursus maritimus). However, during a scientific survey in the ice
      area of the northern Barents Sea east of Svalbard in June 1995, an unexpectedly
      high number of polar bears were observed feeding on harp seal (Phoca
      groenlandica) carcasses. Samples of both harp and ringed seals were obtained and
      organochlorine (OC) occurrence and pattern in these two potential polar bear prey
      species were determined. Significantly higher OC concentrations were found in
      harp seals, as compared to the ringed seals. All animals in the northern harp
      seal group were lean specimens in late moult. The industrial chemicals,
      polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB), and the OC
      pesticides bis-2,2,(chlorophenyl)-1,1,1-trichloroethanes (DDTs),
      hexachlorocyclohexanes (HCHs), and chlordanes (CHLORs) were analysed in blubber.
      The concentrations of sigma PCB (sum of concentrations of 16 PCB congeners) and
      sigma DDT (sum of concentrations of p,p'-DDT and p,p'-DDE) in the northern harp
      seal group ranged from 2093 to 20,382 and 1460 to 10,381 ng g-1 lipid weight,
      with mean concentrations of 11,133 and 6847 ng g-1 lipid weight, respectively.
      The mean concentrations of the CHLORs, oxychlordane and trans-nonachlor, were
      1311 and 3743 ng g-1 lipid weight, respectively, while the mean concentrations of
      HCB and HCH isomers (alpha-, beta- and gamma-HCH) were all < 500 ng g-1 lipid
      weight. No significant difference was found in the mean total blubber mass
      between the two seal species when collected in June. This indicates that polar
      bears preying on harp seals instead of ringed seals at this time of the year
      could accumulate significantly higher PCB concentrations. We suggest that polar
      bears feeding along the ice-edge east of Svalbard in May and June preferentially
      prey on harp seals instead of ringed seals, and that this may partly explain the
      variation in PCB concentrations among polar bears from the Norwegian Arctic. An
      hypothesis is that the harp seal may function as a transport vector of OCs into
      the high Arctic environment.

PMID- 11285737
TI  - Factors that influence the accumulation of copper and cadmium by transplanted
      eastern oysters (Crassostrea virginica) in the Patuxent River, Maryland.
AB  - To investigate the continued accumulation of copper and cadmium by oysters in the
      Patuxent River, MD, which have been at high levels since at least the mid 1960s,
      hatchery-raised Eastern oysters were transplanted into trays at four sites in the
      upper estuary. At each site two groups of oysters were used to determine growth
      and mortality, and another group was sampled for meat condition, metal
      concentration and body burden. Copper in oysters in the discharge of a coal-fired
      power plant was significantly greater than at all other sites, but maximum
      concentration of 310 micrograms g-1 was well below the maximum of 1880 micrograms
      g-1 detected in 1982. Cadmium levels were also significantly greater in the
      discharge than at the other sites, but probably because of higher discharge
      temperatures. Trace metal loadings, the local salinity gradient and the higher
      temperatures caused by power plant operation all appear to contribute to metal
      accumulation by oysters in the upper Patuxent estuary.

PMID- 11285738
TI  - Evidence for two pathways of thiosulfate oxidation in Starkeya novella (formerly
      Thiobacillus novellus).
AB  - The pathway of thiosulfate oxidation in the facultatively chemolithotrophic,
      sulfur-oxidizing bacterium Starkeya novella (formerly Thiobacillus novellus) has
      not been established beyond doubt. Recently, isolation of the sorAB genes, which
      encode a soluble sulfite:cytochrome c oxidoreductase, has been reported,
      indicating that a thiosulfate-oxidizing pathway not involving a multienzyme
      complex may exist in this organism. Here we report the cloning and sequencing of
      the soxBCD genes from S. novella, which are closely related to the corresponding
      genes encoding the thiosulfate-oxidizing multienzyme complex from Paracoccus
      pantotrophus. These findings suggest two distinct pathways for thiosulfate
      oxidation in S. novella. The expression of sorAB and soxC in cells grown on
      thiosulfate- and/or glucose-containing media was studied by Western blot
      analysis. The results showed that the SorAB protein is synthesized in the
      presence of thiosulfate irrespective of the presence of glucose. In contrast, the
      SoxC protein is subject to repression by glucose; the repression, however,
      appears to be dependent on the relative amounts of glucose and thiosulfate
      present. The regulatory effects observed for the expression of sorAB are likely
      to be mediated by an extracytoplasmic function sigma factor encoded by the sigE
      gene identified upstream of sorAB.

PMID- 11285739
TI  - Regulative fine-tuning of the two novel DAHP isoenzymes aroFp and aroGp of the
      filamentous fungus Aspergillus nidulans.
AB  - Two novel genes, aroF and aroG, from the filamentous fungus Aspergillus nidulans
      were isolated and the regulative fine-tuning between the encoded, differentially
      regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthases was
      analyzed. A wide range of DAHP synthase isoenzymes of various organisms are
      known, but only a few have been characterized further. DAHP synthases (EC
      4.1.2.15) catalyze the first committed step of the shikimate pathway, which is a
      putative target for anti-weed drugs. The reaction is the condensation of
      erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to yield DAHP. The two
      purified DAHP synthases showed different affinities for the substrates: 175
      microM for PEP and 341 microM for E4P for the aroFp isoenzyme and weaker
      affinities of 239 microM (PEP) and 475 microM (E4P) for the aroGp isoenzyme. The
      enzymes are differentially regulated by tyrosine (aroFp) and phenylalanine
      (aroGp). The calculated kcat values are 7.0 s-1 for the tyrosine-inhibitable
      (aroFp) and 5.5 s-1 for the phenylalanine inhibitable (aroGp) enzyme. Tyrosine is
      a competitive inhibitor of the aroFp DAHP synthase in its reaction with PEP.
      Phenylalanine is a competitive inhibitor of the isoenzyme aroGp in its reaction
      with E4P. Both enzymes are inhibited by the chelating agent EDTA, which indicates
      a metal ion as cofactor.

PMID- 11285740
TI  - The Aspergillus nidulans homoaconitase gene lysF is negatively regulated by the
      multimeric CCAAT-binding complex AnCF and positively regulated by GATA sites.
AB  - In beta-lactam-antibiotic-producing fungi, such as Aspergillus (Emericella)
      nidulans, L-alpha-aminoadipic acid is the branching point of the lysine and
      penicillin biosynthesis pathways. To obtain a deeper insight into the regulation
      of lysine biosynthesis genes, the regulation of the A. nidulans lysF gene, which
      encodes homoaconitase, was studied. Band-shift assays indicated that the A.
      nidulans multimeric CCAAT-binding complex AnCF binds to two of four CCAAT motifs
      present in the lysF promoter region. AnCF consists at least of three different
      subunits, designated HapB, HapC, and HapE. In both a delta hapB and a delta hapC
      strain, the expression of a translational lysF-lacZ gene fusion integrated in
      single copy at the chromosomal argB gene locus was two to three-fold higher than
      in a wild-type strain. These data show that AnCF negatively regulates lysF
      expression. The results of Northern blot analysis and lysF-lacZ expression
      analysis did not indicate a lysine-dependent repression of lysF expression.
      Furthermore, mutational analysis of the lysF promoter region revealed that two
      GATA sites matching the GATA consensus sequence HGATAR positively affected lysF
      lacZ expression. Results of Northern blot analysis also excluded that the global
      nitrogen regulator AreA is the responsible trans-acting GATA-binding factor.

PMID- 11285741
TI  - Analysis of a 2,4,6-trichlorophenol-dehalogenating enrichment culture and
      isolation of the dehalogenating member Desulfitobacterium frappieri strain TCP-A.
AB  - An anaerobic, 2,4,6-trichlorophenol ortho-dehalogenating mixed culture was
      enriched from sediment of the river Saale (Germany). Two isolated dechlorinating
      colonies (MK1 and MK2) consisted of rods of different lengths and thicknesses,
      indicating heterogeneity. Following subcultivation with thiosulfate as
      alternative electron acceptor and cocultivation with Clostridium celerecrescensT,
      the 2,4,6-trichlorophenol-dehalogenating bacterium Desulfitobacterium frappieri
      strain TCP-A was isolated and characterized regarding its taxonomic properties
      and the spectrum of chlorophenols that it dehalogenated. Four other bacterial
      strains were coenriched and identified as organisms with closest phylogenetic
      relatedness to the Clostridium type strains C. indolis, C. glycolicum, C.
      hydroxybenzoicum and C. sporosphaeroides (16S rDNA sequence identities of 99.5,
      99.2, 94.4, and 93.5%, respectively). Amplified ribosomal DNA restriction
      analysis of the original dehalogenating cultures MK1 and MK2 (when not exposed to
      thiosulfate) confirmed the microbial heterogeneity and revealed the presence of
      two additional species related to the type strains of C. celerecrescens and
      Clostridium propionicum. Only one copy of the 16S rRNA genes of
      Desulfitobacterium frappieri in each of the clone libraries of MK1 and MK2
      (containing 136 and 56 clones, respectively) was found by dot-blot hybridization,
      suggesting a relatively low number of the dehalogenating bacterium within the
      enrichment culture.

PMID- 11285742
TI  - The Rhizobium leguminosarum bv. trifolii pssB gene product is an inositol
      monophosphatase that influences exopolysaccharide synthesis.
AB  - The pssB gene of Rhizobium leguminosarum bv. trifolii encodes a protein of 284
      amino acids with sequence similarity to eukaryotic inositol monophosphatases. The
      gene was cloned and overexpressed in Escherichia coli. The purified gene product
      of pssB showed inositol monophosphatase activity with a Km of 0.23 mM, and a Vmax
      of 3.27 mumol Pi min-1 (mg protein)-1. Its substrate specificity, Mg+2
      requirement, Li+ inhibition, and subunit association (dimerization) were studied
      and compared to those of other inositol monophosphatases. Western immunoblotting
      with anti-PssB antibodies showed the presence of PssB in R. leguminosarum bv.
      trifolii strain TA1 and lack of this protein in the pssB mutant strain Rt12A. The
      presence of PssB protein in R. leguminosarum bv. trifolii TA1 was correlated with
      phosphatase activity with myo-inositol 1-phosphate as a substrate. Evidence for a
      regulatory function of PssB protein in exopolysaccharide (EPS) synthesis is
      presented. The mutation in pssB caused EPS overproduction, and introduction of
      pssB into the wild-type TA1 strain reduced EPS synthesis. The changes in the
      level of EPS production were correlated with a non-nitrogen-fixing phenotype of
      rhizobia.

PMID- 11285743
TI  - Mutants in the nodFEL promoter of Rhizobium leguminosarum bv. viciae reveal a
      role of individual nucleotides in transcriptional activation and protein binding.
AB  - The highly conserved nod box sequence in the promoters of the inducible
      nodulation genes of rhizobia is required for transcription activation together
      with NodD, a LysR-type transcriptional regulator, and a flavonoid as a coinducer.
      DNA fragments containing nod box sequences form two binding complexes when crude
      preparations of Rhizobium leguminosarum bv. viciae are used: a NodD-dependent and
      an additional, NodD-independent complex. The role of individual nucleotides in
      the conserved nod box sequence in complex formation and in nodulation gene
      expression was investigated by introducing 13 individual base-pair substitutions
      in the nodF nod box of R. leguminosarum bv. viciae and studying their effect on
      promoter activity and protein-DNA complex formation. Two mutants showed decreased
      NodD binding and decreased promoter activity. Five mutants showed a NodD
      dependent complex as with the wild-type nodF nod box, whereas their promoter
      activity was severely reduced after induction. This result is in agreement with
      earlier observations that NodD DNA binding also occurs in the absence of inducer.
      Four mutants were impaired in the formation of the NodD-independent retardation
      complex. Three of them showed no alterations in promoter activity, meaning that
      no specific role for the protein forming the NodD-independent complex could be
      established. The two mutants in the highly conserved LysR motif of the nod box
      were unable to direct coinducer-dependent promoter activity but, unexpectedly,
      their retardation patterns were not altered. The remaining two mutants showed
      constitutive promoter activity. The results are discussed in terms of the
      relevance of conserved nucleotides and motifs identified in the nod box.

PMID- 11285745
TI  - Inheritance of the replication complex: a unique or common phenomenon in the
      control of DNA replication?
AB  - Early models of the regulation of initiation of DNA replication by protein
      complexes predicted that binding of a replication initiator protein to a
      replicator region is required for initiation of each DNA replication round, since
      after the initiation event the replication initiator should dissociate from DNA.
      It was, therefore, assumed that binding of the replication initiator is a signal
      for triggering DNA replication. However, more recent investigations have revealed
      that in many replicons this is not the case. Studies on the regulation of the
      replication of plasmids derived from bacteriophage lambda demonstrated that, once
      assembled, the replication complex can be inherited by one of the two daughter
      plasmid copies after each replication round and may function in subsequent
      replication rounds. Since this DNA-bound protein complex bears information about
      specific initiation of DNA replication, this phenomenon has been called "protein
      inheritance." A similar phenomenon has recently been reported for oriJ-based
      plasmids. Moreover, the current model of the initiation of DNA replication in the
      yeast Saccharomyces cerevisiae proposes that the origin recognition complex (ORC)
      remains bound to one copy of the ori sequence (the ARS region) after initiation
      of DNA replication. Thus, it seems plausible that protein inheritance is not
      unique for lambda plasmids, but may be a common phenomenon in the control of DNA
      replication, at least in microbes.

PMID- 11285744
TI  - The clc element of Pseudomonas sp. strain B13 and other mobile degradative
      elements employing phage-like integrases.
AB  - Genes for metabolic pathways in bacteria that degrade aromatic or aliphatic
      pollutants have mostly been confined to either plasmid DNAs or to the chromosome.
      For a few pathways, including classical pathways for chlorocatechol and biphenyl
      degradation, recent evidence has been obtained for location of the pathway genes
      on mobile DNA elements which employ phage-like integrases. This enables the DNA
      elements to integrate into specific sites on the chromosome and yet to excise and
      transfer to other host bacteria. This mini-review gives an overview of those
      elements and their relationship to an increasing number of phage-like elements
      associated with bacterial virulence.

PMID- 11285746
TI  - Denitrification at extremely high pH values by the alkaliphilic, obligately
      chemolithoautotrophic, sulfur-oxidizing bacterium Thioalkalivibrio denitrificans
      strain ALJD.
AB  - Thioalkalivibrio denitrificans is the first example of an alkaliphilic,
      obligately autotrophic, sulfur-oxidizing bacterium able to grow anaerobically by
      denitrification. It was isolated from a Kenyan soda lake with thiosulfate as
      electron donor and N2O as electron acceptor at pH 10. The bacterium can use
      nitrite and N2O, but not nitrate, as electron acceptors during anaerobic growth
      on reduced sulfur compounds. Nitrate is only utilized as nitrogen source. In
      batch culture at pH 10, rapid growth was observed on N2O as electron acceptor and
      thiosulfate as electron donor. Growth on nitrite was only possible after
      prolonged adaptation of the culture to increasing nitrite concentrations. In
      aerobic thiosulfate-limited chemostats, Thioalkalivibrio denitrificans strain
      ALJD was able to grow between pH values of 7.5 and 10.5 with an optimum at pH
      9.0. Growth of the organism in continuous culture on N2O was more stable and
      faster than in aerobic cultures. The pH limit for growth on N2O was 10.6. In
      nitrite-limited chemostat culture, growth was possible on thiosulfate at pH 10.
      Despite the observed inhibition of N2O reduction by sulfide, the bacterium was
      able to grow in sulfide-limited continuous culture with N2O as electron acceptor
      at pH 10. The highest anaerobic growth rate with N2O in continuous culture at pH
      10 was observed with polysulfide (S8(2-)) as electron donor. Polysulfide was also
      the best substrate for oxygen-respiring cells. Washed cells at pH 10 oxidized
      polysulfide to sulfate via elemental sulfur in the presence of N2O or O2. In the
      absence of the electron acceptors, elemental sulfur was slowly reduced which
      resulted in regeneration of polysulfide. Cells of strain ALJD grown under anoxic
      conditions contained a soluble cd1-like cytochrome and a cytochrome-aa3-like
      component in the membranes.

PMID- 11285747
TI  - [The status of vaccine preventable diseases in Germany].
AB  - The European members of the World Health Assembly (WHO) adopted the goal of
      eliminating poliomyelitis by the year 2000 (certification 2003), tetanus of the
      newborn by 2005 and measles by 2007 (certification 2010). Regarding the reduction
      by 2010 diphtheria, hepatitis B, pertussis and rubella syndrome are in the
      foreground of discussions. As WHO-member Germany looks after these aims with
      growing acceptance, too. The current situation of the specific target illnesses
      is differentiated in the eastern and western part of Germany. While the final
      stage of certification for a polio-free region in the whole of Germany has been
      reached and there have only been single illnesses of diphtheria and tetanus for
      years, there are reported more than 5,000 illnesses of hepatitis B every year
      with an estimated number of unknown cases of at least 15,000 clinically
      manifested illnesses and a high age specific incidence rate for people who are 20
      40 years old. The incidence rate in the eastern federal states is lower than in
      the western federal states owing to a smaller portion of endangered risk groups
      in the population. The trend on the whole is declining. Useful epidemiological
      data of measles and pertussis are currently only available in the eastern federal
      states of reunited Germany. To control measles a national intervention programme
      "measles, mumps, rubella" was started. The aim of this programme is to reduce the
      illnesses of measles in Germany from currently 50 to at first 5 illnesses per
      100,000 inhabitants. In the eastern German federal states the situation is still
      better than in the western federal states. However, a permanent lower incidence
      rate of less than 1/100,000 inhabitants has not been reached after 1990.
      Pertussis is an example for the consequences of different vaccination strategies
      in East and West. The estimated illness rates in the western federal states are
      at 80-100/100,000 inhabitants. In the eastern federal states a continuous
      increase of incidence rates of more than 5 per 100,000 inhabitants has been
      noticed since 1991. For a permanent reduction of incidence rates of infectious
      diseases which are preventable by vaccination, provable high vaccination coverage
      and an effective epidemiological control are necessary.

PMID- 11285748
TI  - [Epidemiology of hantaviruses in Baden-Wurttemberg].
AB  - Hantavirus, originally named after the Hantaan River in Korea, is the aetiologic
      agent for the Hemorrhagic Fever with Renal Syndrome (HFRS) in the asian region,
      in the Americas for the Hantavirus Pulmonary Syndrome  (HPS). In Middle Europe
      hantaviruses are responsible for the "Nephropathia Epidemica" (NE), a mild form
      of HFRS. Hantaviruses belong to the family of Bunyaviridae. Like other members of
      this family their genome consists of three segments of single stranded RNA (ss
      RNA) leading to various subtypes, strongly associated with different rodent
      hosts. There are two major groups, the hantaan lineage harbored by murine rodents
      and the Puumala lineage harbored by arvicolidae ("old world") and sigmodontidae
      ("new world"). Infected rodents may develop chronic infections for months or even
      life-long and may shed infectious virus with urine and feces. The primary mode of
      infection of man occurs by inhaling contaminated aerosols or soil particles. The
      collection of epidemiologic data in the state of Baden-Wurttemberg was realized
      in three different steps: Collection and localisation of clinical cases (n = 62):
      A concentration of clinical cases in the middle of the state was found. The
      examination of the seroprevalence of exposed persons: By the examination of 4000
      sera from forest workers, a seroprevalence with an average of 2.1% was found. In
      the districts of Reutlingen and Tubingen seroprevalences up to 9% were found.
      This leads to the assumption that there are endemic areas. Epidemiologic studies
      of reservoir hosts: Serologic surveys of rodents (n = 1150) in the described
      areas yielded to a seroprevalence up to 10-30%. Virus carriers were determined
      with RT-PCR and nested-PCR testing. The prevalence in the rodent population
      showed an average of 10%. The isolated subtypes were all identified as members of
      the Puumala-lineage. The origin of sporadic infections with Hantavirus of the
      Hantaan-lineage in Baden-Wuerttemberg is still unknown.

PMID- 11285749
TI  - [Community health documentation as an instrument for further developing
      recommendations in community health].
AB  - The local health conference in a North Rhine-Westphalian county of Germany has
      made proposals to improve immunisation rates against measles, mumps and rubella.
      Another target was to prevent decubitus by elderly patients in hospitals, nursing
      homes and in the outpatient nursing. Local public health reports were the basis
      for the development of (local) health targets in the health conference. The data
      of 12,830 immunisation papers from 11-19-year old students showed immunisation
      rates against measles, mumps and rubella from 44% to 14% depending on the type of
      school. Virus hepatitis B immunisation rates are 32% in the county. There were
      also great differences between local towns of the county. The decubitus data
      showed rates from 2.3% in nursing homes to 5.1% in the outpatient sector. It is
      also shown that health reports and health conferences help to improve local
      conditions in public and individual health.

PMID- 11285750
TI  - [Evaluating health risk tolerance and risk assessment].
AB  - According to current regulations, major projects are subject to an environmental
      impact assessment. Within this framework, not only ecological criteria have to be
      met, but also the possible health impact for the exposed population must
      assessed. In the absence of limit values for carcinogenic substances in the air,
      the health impact assessment can be based on quantitative risk assessment. This
      technology was formerly developed for the assessment of cancer risk imposed by
      existing environmental exposures, but it is also suitable for the prediction of
      future exposures and their health consequences. This is demonstrated by using a
      planned toxic waste incinerator as a model.

PMID- 11285751
TI  - [Risk evaluation and construction planning in a high pollution region].
AB  - More than thousand years of mining and metallurgical engineering in the Harz
      mountains is the reason why heavy metal contamination in soil and air by arsenic,
      cadmium and lead is a problem in parts of the Harz region. Risk assessment is the
      duty of the district community physician. Checkup of sanitary conditions in
      habitat planning is very important and the basis for the development of healthy
      cities.

PMID- 11285752
TI  - [Environmental medicine in public health service--a social responsibility and its
      consequences].
AB  - The special committee for "Environmental Medicine" established by the Federal
      Association of Doctors in the German Public Health Service presents its paper
      entitled "Environmental Medicine in the Public Health Service--A Social
      Responsibility and its Consequences: Propositions with regard to the situation,
      aims, strategies, and opportunities for action". The paper includes core ideas
      and responsibilities in the public health service. It aims at providing a number
      of guidelines for implementing "Environment and Health" ("Umwelt und
      Gesundheit"), an action programme by the Federal Ministry of Environmental
      Protection and the Ministry of Health, as well as "Health 21" ("Gesundheit 21"),
      the framework concept "Health for all" for the WHO's European Region. The paper
      also aims at initiating and facilitating steps for joint action by the Public
      Health Service. These theses were passed on to Mrs. Andrea Fischer, the Federal
      Minister of Health, during a meeting with the Board of the Association. In
      Germany, environment-related public health protection is well established in the
      Public Health Departments and state institutes/departments within the scope of
      public health provision and disease prevention. Typical responsibilities include
      environmental hygiene and environment-related medical services which have
      increased in importance. The range of responsibilities and its current political
      importance are a result of environment-related public health risks, the social
      situation of the population, also with regard to health issues, and the scope of
      responsibilities and competencies by doctors and staff in the public health
      departments. With the people's demands for health, quality of life and life
      expectancy, this need for action increases. In this paper, judicial,
      professional, and personal consequence are presented which arise as public health
      authorities assume these responsibilities.

PMID- 11285753
TI  - [Psychological disorders and environmental pollution].
AB  - In the past years Environmental Medicine has established itself in the
      departments of community medicine. The clients of these health offices as well as
      those attending other Environmental Outpatient Departments and who suffer from
      anxiety in connection with environmental pollution show increasingly psychomatic
      and even psychiatric disturbances. This paper demonstrates, from the
      psychiatrists as well as the environmental physicians point of view, the
      relationship between psychological disturbances and environmental pollution in a
      typical case-history. The differentiation between possibly toxically induced
      symptoms and psychologically caused symptoms will be made clear. The aim of this
      interdisciplinary paper is to contribute towards reducing contact anxiety between
      Psychiatry und Environmental Medicine also to reduce the clients' fears of
      psychiatrisation and thus to facilitate therapeutic intervention.

PMID- 11285754
TI  - [Exposure status of East and West German households with house dust mites and
      fungi].
AB  - The interrelation between biological pollution of indoor spaces and health
      disorders, allergic symptoms and health issues in general is well known. Besides
      animal epithelia, the exposure to house dust mites and mould fungi is considered
      a serious risk factor. In the scope of a comparative study involving school
      beginners in East and West Germany (launched in 1991), dust was vacuumed from a
      total of 218 mattresses of children's beds and checked for their content of house
      dust mites and mould fungi. This investigation aimed at assessing the degree of
      exposure, to determine regional differences, if any, and to uncover the
      correlation between exposure and symptoms. Dust mite infestation was highest in
      the small town of Borken in Westphalia (in 86% of the specimens > 2 micrograms
      mite allergens/g of dust) and lowest in Magdeburg in Saxony-Anhalt (55.3%). Total
      concentrations of mould fungi varied from 1.4 x 10(3) CFU/g of dust and 300 x
      10(3) CFU/g of dust with a geometric mean of 26.5 x 10(3) CFU/g of dust. A total
      of 41 different genera/species were identified. Most frequent were the following
      genera: Penicillium, Eurotium, Aspergillus, Alternaria, Epicoccum and
      Cladosporium. The importance of individual factors influencing was confirmed.
      Humidity decreases the higher the flat is situated in a building. This partly
      explains the differences in concentrations between Borken where children live
      mainly on the ground floor, and the other cities with taller buildings. Spores of
      mould fungi were discovered more frequently in mattresses from humid flats. An
      association between biological indoor space factors and some allergological
      parameters seemed obvious, however, due to the small size of the test group most
      of them were not significant.

PMID- 11285755
TI  - ["Data for action" from the viewpoint of the Regional Dental Board and the
      Regional Professional Group for Dental Health].
AB  - Lecture by the President of the Landeszahnarztekammer (Regional Chamber of Dental
      Surgeons) Baden Wuerttemberg and Chairman of the Landesarbeitsgemeinschaft
      Zahngesundheit (Regional Task Force for Dental Health) on the occasion of the
      50th scientific convention "Healthy into the Future" of the Federal Association
      of Doctors and Dentists in the Public Health Sector. This lecture by Dr. Rudiger
      Engel highlights the planned goals of the Landesarbeitsgemeinschaft
      Zahngesundheit (Regional Task Force for Dental Health) as well as those of the 37
      associated Regional Task Forces for Dental Health up to year 2003.

PMID- 11285756
TI  - [Sociodental indicators in children and adolescents].
AB  - Sociodental indicators are measures for the psychological and social impact of
      dental diseases. They add the subjective views of patients to professionally
      defined clinical indices. The article describes the theoretical and empirical
      background for the development of those indicators and states which indicators
      have been used so far in Germany. Sociodental indicators may be used in oral
      health promotion for children and adolescents to assess their problems, to better
      understand their experiences and perceptions and to demonstrate the need for
      dental prevention to the public and financing institutions. The indicators are
      less suitable for planning purposes and for evaluating health promotion, because
      they represent effects which are too remote from the intervention itself and are
      influenced by too many co-factors. Finally, a conceptual framework for indicators
      of psychosocial impacts on children is presented.

PMID- 11285757
TI  - [Effective of preventive programs on oral hygiene of adults and school children].
AB  - The improvement of dental hygiene is considered to be one of the most important
      measures in dental health education. Hence, it was the aim of the present study
      to investigate the influence of two similar preventive programmes on oral hygiene
      performed in adults and schoolchildren. In the adult study, the oral hygiene
      indices PI (Quigley-Hein) and API (Lange) could be significantly improved after
      six months by an individualized preventive programme performed every three
      months. Besides repeated instructions and motivations in oral hygiene, the
      programme included professional toothcleaning. In contrast, nine-year old
      schoolchildren showed no improvement in the oral hygiene indices PI and PBI
      (Muhlemann and Son) after applying a similar programme over three years. For the
      PI, even a deterioration from 1.86 at the beginning of the study to 2.65 at the
      final examination was seen. Other authors were more successful by applying a
      programme without professional toothcleaning but with inclusion of the parents.
      It is therefore concluded that children should be educated to oral self-care by
      including their parents and by taking their status of psychological development
      into account.

PMID- 11285758
TI  - [Autopsy--as superfluous as goiter?].

PMID- 11285759
TI  - [Dysplastic bronchial changes as etiology of sudden death. A plea for the
      necessity of diagnostic autopsy].
AB  - BACKGROUND AND OBJECTIVE: Legal regulations of cadaver examination and autopsy
      require fundamental changes. Regulations that result in up to 75% errors in the
      recorded cause of death on the death certificate make no sense. As an example,
      rare disease of bronchial malformation may cause sudden, unexpected death but is
      only detectable at autopsy with subsequent histological examination. PATIENTS AND
      METHODS: In an series of 17.204 autopsies (from 1980 to 1999) 894 cases of
      sudden, unexpected death were examined. In 28 cases (3.1%) only histological
      examination of the lungs provided the cause of natural death. RESULTS: Bronchial
      dysplasia may be clinically silent and leads to focal panazinar emphysema and
      atelectasis due to chronic airflow obstruction and an "air trapping" mechanism.
      Subsequent pulmonary hypertension results in a cor pulmonale, which may fail
      suddenly and unexpectedly. CONCLUSION: The diagnostic problems of natural death
      justifies the performance of an autopsy. This fact should be recognized legally.
      Using the example of bronchial malformation, it is shown that only an autopsy may
      reveal the exact cause of death.

PMID- 11285760
TI  - [Can pathological left ventricular hypertrophy in arterial hypertension be
      distinguished from physiological hypertrophy caused by sports?].
AB  - BACKGROUND AND OBJECTIVE: Patients with hypertensive heart disease and left
      ventricular hypertrophy demonstrate impaired left ventricular diastolic filling.
      Aim of this study was to find out if physiological left ventricular hypertrophy
      induced by endurance training causes abnormal left ventricular systolic and
      diastolic filling. METHODS: We examined 42 athletes with left ventricular
      hypertrophy due to endurance training (aged 25 +/- 7 years), 31 patients with
      left ventricular hypertrophy due to hypertensive heart disease (aged 28 +/- 6
      years) and 20 untrained, healthy subjects (controls, aged 26 +/- 8 years) by
      conventional echocardiography and calculated left ventricular muscle mass and
      fractional shortening. In addition the following Doppler-echocardiographic
      parameters were measured: maximal early and late velocity of diastolic filling,
      ratio of maximal early and late velocity of diastolic filling, acceleration and
      deceleration time and isovolumetric relaxation time. RESULTS: All three study
      groups showed normal fractional shortening. Conventional echocardiography
      revealed a higher left ventricular muscle mass in the two study groups as
      compared to the controls (controls: 119 +/- 12 g, athletes: 225 +/- 18 g*;
      hypertensive patients: 216 +/- 16 g*; * p < 0.01 versus controls). In the
      athletes with physiological left ventricular hypertrophy a normal left
      ventricular diastolic filling pattern was documented (VE: 0.64 +/- 0.1 m/s; VA:
      0.51 +/- 0.2 m/s). In hypertensive heart disease a diastolic dysfunction in terms
      of a delayed relaxation pattern with a decrease of maximal early velocity of
      diastolic filling (VE: 0.45 +/- 0.09 m/s) and a compensatory increase of the
      maximal late velocity of diastolic filling (VA: 0.54 +/- 0.1 m/s) was
      demonstrated. CONCLUSION: In pathological left ventricular hypertrophy due to
      hypertensive heart disease a pathological diastolic filling pattern was
      documented. In athletes with physiological left ventricular hypertrophy a normal
      left ventricular diastolic filling pattern was revealed. Thus Doppler
      echocardiographic parameters of left ventricular diastolic function can be of
      diagnostic importance for discriminating between pathological and physiological
      left ventricular hypertrophy.

PMID- 11285761
TI  - [Angiographically unexplained myocardial ischemia in high grade coronary stenosis
      with main stem involvement in intravascular ultrasound].
AB  - HISTORY AND ADMISSION FINDINGS: For seven weeks a 57-year-old man had been
      complaining of recurrent non-radiating retrosternal pain and pressure on
      slightest exertion. Admission physical examination was unremarkable except for
      evidence of peripheral vascular disease. Cardiovascular risk factors were
      hypertension, hyperlipoproteinaemia and obesity. INVESTIGATIONS: The resting ECG
      was unremarkable. Objective signs of myocardial ischaemia were produced in the
      exercise ECG (angina at 100 Watt, negative T waves in V2 to V6 and borderline S-T
      depression in V4). Myocardial scintigraphy showed reversible reduced perfusion of
      the anterior wall near the apex and also of the apex and septum. Left ventricular
      (LV) angiography demonstrated a normally contracting LV, while selective coronary
      angiogram revealed a 20% reduction in caliber of the proximal branch of the
      anterior interventricular branch (AIVB), with otherwise normal coronary arteries.
      Subsequent intravascular ultrasound (IVUS) showed a circular echo-poor 80%
      stenosis at the origin of the AIVB with extension to the main stem. TREATMENT AND
      COURSE: A bypass from the internal mammary artery to the AIVB and an
      aortocoronary venous bypass to the intermediate branch were performed. The
      patient was free of symptoms postoperatively. CONCLUSION: If cases where there is
      a discrepancy between clinical and coronary angiographic findings--the latter
      being unclear or inconsistent, especially in the area of the left main stem,
      bifurcations or vessel origin--IVUS may contribute decisively to demonstrating
      coronary anatomy or pathology, and to indicating the type of revascularizing
      measures.

PMID- 11285762
TI  - [Sj"ogren syndrome associated with pernicious anemia. Systemic versus organ
      specific autoimmune disease].

PMID- 11285763
TI  - [Critical aspects of current methadone treatment in Germany].

PMID- 11285764
TI  - [Therapy possibilities in AA amyloidosis in long-term Crohn disease].

PMID- 11285765
TI  - [What may the insurance carrier change in the contract of the medical department
      head? Decision of the Hameln court 23 November 1998].

PMID- 11285766
TI  - [Evidence-biased medicine--or: deceptive safety of the evidence].

PMID- 11285767
TI  - [Evidence-biased medicine--or: the deceptive safety of the evidence].

PMID- 11285768
TI  - [Requirements for patient education exemplified by radiotherapy].
AB  - BACKGROUND: Under existing law which goes back to a decision of the supreme court
      of the German Reich in 1894, any medical intervention, even if performed lege
      artis and successfully, meets the elements of physical injury both in terms of
      civil and criminal law and, thus, is illegal. This unlawfulness can only be
      validly reversed by the patient's informed consent which requires adequate
      effective patient information. METHODS: The relevant principles in patient
      information on potential risks elaborated by the West German administration of
      justice are outlined by 22 these. Subsequently, supreme and highest court
      decisions are listed, briefly summarizing the jurisdiction on patient information
      relevant to radiotherapists. CONCLUSION AND PERSPECTIVES: Tendencies to gain
      financial profit from improper patient information can be resolutely steered
      against right from the start.

PMID- 11285769
TI  - Differentiated thyroid cancer: prognostic factors and influence of treatment on
      the outcome in 441 patients.
AB  - BACKGROUND: Differentiated thyroid cancer (DTC) is a rare tumor entity with
      excellent prognosis. Thus, assessment of the efficacy of different treatment
      modalities requires follow-up for such a long period that the validity of the
      conclusion may be limited because diagnostic and therapeutic standards have
      changed substantially. Accordingly, the indication for external radiotherapy is
      still controversial. The aim of the present retrospective study is to evaluate
      prognostic factors and the influence of treatment on outcome of differentiated
      thyroid cancer from a large data base. PATIENTS AND METHODS: Records of 441
      patients (317 females, 124 males; mean age 46 years) with 270 follicular and 171
      papillary thyroid carcinomas (pT1-4, pN0-3) were reviewed. Treatment was surgery
      in 440, radioiodine therapy in 338, postoperative external radiotherapy (50-60
      Gy) in 223 patients. In 182 cases the three modalities were combined. RESULTS:
      The 5-year actuarial survival rate of the whole study population was 95%, 10-year
      survival 92%. 10-year survival was significantly influenced by: tumor stage (pT1:
      100%, pT2: 94%, pT3: 94%, pT4: 79%; p = 0.0005), age (< 40 years: 100%, 41-60
      years: 91%, > 60 years: 79%; p = 0.0001) and the presence of lymph node
      metastases in the follicular subtype (pN0: 96%, pN1-3: 81%; p = 0.02). No
      significant differences in survival were found according to gender or
      histological subtype. External radiotherapy yielded a non-significant (p = 0.06)
      increase in the 10-year survival rate (87% vs 46%; p = 0.06) in patients with pT4
      tumors (n = 60). CONCLUSION: Prognostic factors predominantly confirmed those
      reported in the literature. Further clinical studies should clarify, if the trend
      towards better survival in irradiated patients with pT4 tumors can be confirmed
      in larger patient groups.

PMID- 11285770
TI  - [Mediastinal Hodgkin lymphomas in computerized tomography. Comparison of exact CT
      assisted volumetry and volume assessment using simple geometric models].
AB  - BACKGROUND: The importance of the size of the primary tumor in lymphomas and its
      size after treatment is still uncertain. Assuming a prognostic relevance, an
      assessment of tumor volume before and after induction of chemotherapy has been
      performed in the pediatric Hodgkin's disease study (HD-90). Since an exact CT
      scan-based volumetric tumor assessment is time-consuming and in some centers not
      possible, the tumor volume is often estimated based on simple geometric
      approximations. Aim of this study was the development of an easy to apply and
      nearly exact model of volume estimation compared to CT-scan-based tumor volume
      measurements. MATERIAL AND METHODS: Thirty computed tomographies (CT) of
      mediastinal Hodgkin lymphomas of children aged 5 to 16 years have been examined.
      The CT scans were digitalized using a CCD camera combined with a frame grabber.
      Applying the Global Lab image software, the true tumor volume was determined
      excluding local organs, which did not belong to the lymphoma. Subsequently,
      volumes were assessed using simple geometric models (block, ellipsoid, octaeder)
      by using the maximum diameters of the tumor. The differences between the volume
      of the geometric models and the true volume, based on the CT scan evaluation,
      were compared. RESULTS: The maximum diameters of a tumor can be used to calculate
      its volume based on simple geometric models. The model "block" overestimates the
      volume by 89 to 268%. The model "ellipsoid" overestimates the volume on average
      by 29%. The model "octaeder" underestimates the volume on average by 18%. A
      division of the block volume by 2.3 approximated the geometric closest to the
      true volume: the average volume was overestimated by 2% in tumors with a volume
      larger than 20 ml. No model was sufficient to approximate tumors with a volume of
      less than 20 ml. CONCLUSIONS: For the estimation of tumor volumes in mediastinal
      Hodgkin lymphomas exceeding 20 ml, the formula "block/2.3" results in the closest
      approximation compared to the true volume. In the course of clinical studies it
      might be helpful to apply this formula to determine the prognostic relevance of
      the tumor size and its development under therapy.

PMID- 11285771
TI  - Clinical relevance of positron emission tomography (PET) in treatment control and
      relapse of Hodgkin's disease.
AB  - BACKGROUND: In Hodgkin's disease accurate restaging is important to assess
      treatment results and may eventually provide a basis for further therapeutic
      strategies. A typical dilemma after treatment of Hodgkin's disease with
      radiographically persistent lymphoma is the differentiation between sterilized
      residual mass and viable tumor. Positron emission tomography (PET) has been
      described as a reliable tool to identify active lymphoma. Aim of the present
      study was to assess the accuracy and clinical relevance of PET for treatment
      control and in the situation of a suspected relapse of Hodgkin's disease.
      PATIENTS AND METHODS: 63 patients (32 men, 31 women, mean age 41.5 years) with
      Hodgkin's disease were investigated with FDG-PET. In 51 patients 63 PET studies
      were performed as a treatment control (group 1) after primary therapy. 17
      patients (5 of whom preexamined in group 1) underwent 18 PET scans for
      confirmation of suspected relapse (group 2). PET was performed with a dedicated
      whole-body ring scanner. In a retrospective analysis, all FDG-PET scans were
      compared with conventional imaging methods and related to the final diagnosis
      obtained by histology and/or clinical follow-up (mean 22.4 months). RESULTS:
      Group 1: FDG-PET showed an accuracy of 91%, whereas the accuracy of conventional
      imaging was 62%. Group 2: The accuracy for PET was 83% and 56% for conventional
      imaging. CONCLUSION: The present data suggest that PET is a sensitive and
      reliable tool for detection of involved areas of active Hodgkin's disease. The
      accuracy of PET for restaging purpose seems to be superior than conventional
      imaging.

PMID- 11285772
TI  - [Therapy monitoring with 2-(18F)-FDG positron emission tomography after
      neoadjuvant radiation treatment of mouth carcinoma].
AB  - BACKGROUND: Combined protocols of radiation therapy and surgical resection, as
      applied in advanced oral cancer, rely on objective and early assessment of
      treatment response to radiation therapy. Non-responders require immediate radical
      salvage surgery even in spite of substantial operative risks, while complete or
      subtotal response may give reasons for continuing the conservative approach.
      Therefore, we investigated radiation response by FDG-PET for early monitoring of
      oral cancer. PATIENTS AND METHODS: In 30 patients with advanced stages of oral
      cancer (Table 1), FDG-PET (Siemens, ECAT EXACT 922) was performed within 4 weeks
      after completion of preoperative radiation therapy (36 Gy). SUV of tumor regions
      were compared to the histologic degree of tumor regression in complete resection
      specimens. Statistic evaluation included correlation analysis of SUV vs tumor
      regression and ROC analysis for SUV cut-off values. RESULTS: While low FDG
      accumulation was found in tumors with histological complete remission (2.3 +/-
      0.4) as well as in cases of residual tumor (3.4 +/- 1.8), high FDG uptake was a
      rather specific indicator of vital tumor tissue (Figure 2). Significant
      correlation (p = 0.045) between postradiotherapeutic FDG-uptake and histological
      tumor regression was recognized. A SUV > 2.75 as a clinically practicable
      threshold value for the identification of residual vital tumor resulted in a
      specificity of 88%, sensitivity of 68%, a positive predictive value of 94% and a
      negative predictive value of 50% (Figure 3). Based on our actual follow-up data
      we could not confirm a significant correlation between postradiotherapeutic SUV
      and patients' survival. CONCLUSION: Within a standardized protocol, FDG-PET
      recognize treatment response to radiation therapy in oral squamous cell carcinoma
      with a reasonable specificity and thus provides a basis for further therapeutic
      decisions. An increased SUV (> 2.75) may be the rational to justify an aggressive
      surgical approach even when patients face substantial surgical or
      anesthesiological risk. However, the posttherapeutic pattern of glucose uptake
      varies with the applied treatment modalities and has to be explored for the
      protocol applied.

PMID- 11285773
TI  - Prognostic impact of tumor perfusion in MR-imaging studies in Ewing tumors.
AB  - BACKGROUND: Intratumoral hypoxia is associated with poor prognosis in various
      solid tumors. Severe and long-lasting hypoxia results in necrosis. The presence
      of necrosis therefore might also be correlated with unfavorable outcome. This has
      been demonstrated for head and neck cancers, gliomas and adult soft tissue
      sarcomas. We have investigated whether or not the patterns of contrast
      enhancement and the presence of visible necrosis on pretreatment MR images has
      prognostic impact in Ewing tumors. PATIENTS AND METHODS: From December 1993
      though March 1997, 79 patients with Ewing tumors were prospectively analyzed for
      the presence and amount of necrosis in their tumors. The median age was 12 years
      (range 4-30 years). The median follow-up at the time of this analyses was 3
      years. All patients were treated according to the multicentric EICESS-92 protocol
      with multi-agent chemotherapy (VACA or VAIA or EVAIA) and local therapy
      (radiotherapy with 50-60 Gy or surgery or surgery with pre- or postoperative
      irradiation with 45-50 Gy). For the measurement of necrosis, gadolinium contrast
      enhanced T1-weighted MR images were used. Necrosis was defined as non-perfused
      areas in the tumor and the necrotic volume was expressed as percentage of total
      volume. RESULTS: Out of 79 tumors, 10 (13%) showed no necrosis, 30 (38%) had 1
      25% necrosis, 21 (27%) had 26-50% necrosis and the remaining 18 (23%) more than
      50% necrosis. There was a correlation between tumor size and necrosis (p =
      0.001): the median tumor volume increased with amount of necrosis (47 cm3 in non
      necrotic tumors, 59 cm3 vs 280 cm3 vs 284 cm3 for tumors with 1-25% vs 26-50% vs
      > 50% necrosis). Tumor site (central location vs proximal extremities vs distal
      extremities) had no impact on necrosis (p = 0.71). 23 out of 79 patients had
      metastases (M1) at the time of diagnosis. The frequency of metastatic spread
      increased with the amount of necrosis: 1/10 (10%) patients with non-necrotic
      tumors had metastases vs 7/30 (23%) vs 6/21 (28%) vs 9/18 (50%) for tumors with 1
      25% vs 26-50% vs > 50% necrosis. "Unfavorable" metastatic spread (bone or
      multiple metastases) was only noted in patients with high amount of necrosis (>
      25% necrosis) whereas even large tumors did not show unfavorable metastases if
      they contained no or only small amounts of necrosis. All patients with non
      necrotic tumors survived event-free during the observation period. Patients with
      necrotic tumors had a 3-year event-free survival of 55% (p = 0.06 vs tumors
      without necrosis). CONCLUSIONS: The presence of non-perfused (presumably
      necrotic) areas on pretreatment contrast-enhanced MR-images is associated with an
      increased risk of metastases, especially an unfavorable pattern of metastatic
      spread at diagnosis. This observation may be explained by a more aggressive
      biological behavior of hypoxic tumor cells. The small group of patients with non
      necrotic tumors (13%) had an excellent prognosis suggesting that the absence of
      necrosis might be helpful in identifying a very favorable prognostic subgroup in
      Ewing tumors.

PMID- 11285774
TI  - [Value of positron emission tomography in treatment of lymphoma patients].

PMID- 11285775
TI  - [Preoperative staging of non-small-cell bronchial carcinoma with PET].

PMID- 11285776
TI  - [Comparison of various fractionation schedule in curative radiotherapy alone of
      locally advanced head and neck tumors].

PMID- 11285777
TI  - [Role of radiotherapy in induction of myeloid secondary neoplasms after high
      dosage therapy of malignant lymphomas].

PMID- 11285778
TI  - [Inflammatory hypertrophic cranial pachymeningitis].
AB  - DEFINITION: Inflammatory cranial hypertrophic pachymeningitis (ICHP) is a
      fibrosing inflammatory process that thickens the dura mater. This condition is
      increasingly reported owing to the use of CT and MRI. CLINICAL ASPECTS: Chronic
      headache and cranial neuropathies are the main presentations. Generally the
      erythrocyte sedimentation rate is elevated and cerebrospinal fluid is
      inflammatory. DIAGNOSIS: Non-invasive imagery visualizes the thickening of the
      dura mater that may be focal or diffuse. On MRI diffuse intense enhancement due
      to intra cranial hypotension must not be confused with ICHP. Focal thickening of
      the dura may be tumoral. Biopsy of the thickened dura mater is useful for
      confirming the inflammatory nature of the process and for orienting the
      etiological diagnosis. "SECONDARY" ICHP: ICHP has many causes, infectious and
      noninfectious. It may be the presenting manifestation of systemic diseases as
      sarcoidosis or Wegener's granulomatosis. "IDIOPATHIC" ICHP: A diagnosis of
      exclusion, ICHP might be an isolated intracranial localization of multifocal
      fibrosis, an ill-defined autoimmune disease. TREATMENT: A specific treatment is
      indicated in some cases of secondary ICHP. In most cases treatment relies on
      corticosteroids an/or immunosuppressive therapy.

PMID- 11285779
TI  - [Sleep and aging].
AB  - A COMMON DISORDER: Sleep is one of the most often altered functions in elderly
      people. Obviously, insomnia is one of the main complain, inducing benzodiazepine
      (BSD) abuse, but we must keep in mind that sleep apnoea syndrome (SAS) and
      restless legs syndrome (RLS) are also frequent in this group of age. After
      exclusion of the various age-related conditions that could induce sleep
      disorders, we must focalise on primary and secondary sleep disorders. As an
      introduction, methods of sleep analysis are described and qualitative and
      quantitative sleep variables are given. PHYSIOLOGICAL SLEEP: Comparing the sleep
      of elderly people to the one of young adult give us the opportunity to define the
      limits of the physiological sleep aging. It seems that the main age-induced sleep
      disturbances are problems to maintain sleep and chronobiological disorganisation
      of the sleep-wake rhythm, both responsible for insomnia complains. It is
      important to note that SAS and RLS prevalence are correlated with age. Also
      crucial is the complex association between sleep, depression and dementia. These
      interactions are addressed from a diagnostic and a therapeutic point of view.
      THERAPEUTIC APPROACH: Lastly, concerning insomnia we emphasise the importance of
      therapeutic alternative to BZD, responsible for addictions and cognitive
      impairment, mainly behavioural and chronotherapeutic methods (phototherapy,
      melatonin). For clinicians, it is recommended to respect the individual rhythms
      of each elderly patient and to prefer nonpharmacological methods.

PMID- 11285780
TI  - [Therapeutic aspects of cerebral ischemia].
AB  - ACUTE STROKE: At the acute stage of cerebral ischemia, the treatment consists of:
      -general non-specific rules, such as treating a vital emergency, keeping
      biological parameters within normal limits and preventing complications;-
      admission in a stroke unit, to decrease mortality without increasing dependence
      or recurrence risks;--intravenous administration of rt-PA within 3 hours of
      stroke onset in eligible patients;--in patients who are not eligible for rt-PA,
      aspirin (160 to 300 mg) to reduce early recurrence and death, even in atrial
      fibrillation;--decompressive surgery in patients with raised intracranial
      pressure. SECONDARY PROPHYLAXIS: Secondary prevention consists of:--treatment of
      risk factors for stroke;--aspirin (75 to 325 mg), or clopidogrel, or the
      association aspirin-dipyridamole in high-risk subjects without cardiopathy, or
      warfarin in patients with high-risk cardiopathies;--carotid surgery in patients
      selected by clinical and imaging criteria.

PMID- 11285781
TI  - [Primary tuberculosis of the breast].
AB  - BACKGROUND: Despite generalized BCG vaccination, tuberculosis remains a public
      health issue in France. Breast localizations are exceptional and constitute a
      diagnostic and therapeutic challenge. CASE REPORT: A 34-year-old woman who was
      nursing her 3-month old infant underwent emergency surgery for a breast abscess
      that had been incised one month earlier and treated with non-specific antibiotic
      therapy without success. All necrotic tissue was removed. Pathology provided the
      diagnosis of tuberculosis. An anti-tuberculosis regimen (INH + rifampicin + PZA +
      ethambutol for two months followed by INH + rifampicin for 7 months) was
      instituted. The epidemiology search was negative and no extension was found. The
      clinical course was favorable at 6 months. DISCUSSION: Tuberculosis is rarely
      localized in the breast. The main differential diagnosis is breast cancer.
      Pathology examination is required for diagnosis. Anti-tuberculosis antibiotic
      therapy may be associated with surgery in case of extension.

PMID- 11285782
TI  - [Apropos of indications for curarization in anesthesia].

PMID- 11285783
TI  - [Transmissible subacute spongiform encephalopathies. What is really known
      today?].

PMID- 11285784
TI  - [Gait disorders in Parkinson disease. Neuroanatomic and physiologic organization
      of gait].
AB  - GAIT IS A VOLUNTARY, AUTOMATIC AND REFLEX RHYTHMIC ACTIVITY: It is generated by a
      central pattern generator identified from animal models. This spinal gait
      generator (SGG) is controlled by various parts of the central nervous system: the
      descending tracts and locomotor regions of the brainstem, the cerebellum, the
      basal ganglia, the motor and parietal cortex and the hippocampus. Kinesthetic
      inputs which project to the SGG and the cerebellum, play an important role in the
      production of postural reflex responses; vestibular and visual inputs mainly
      control balance. GAIT MAINLY DEPENDS ON THE RELATIONSHIP BETWEEN POSTURE BALANCE
      AND MOVEMENT: As concerns posture each segment is under the control of both
      peripheral and central nervous systems and is used as a system of reference to
      organize movements of adjacent segments. Balance is maintained by sensory inputs
      which provide corrective mechanisms: anticipatory postural responses, reflex
      postural responses and voluntary responses. DIFFERENT DESCRIPTIVE PARAMETERS MAY
      BE PROPOSED: Analysis of kinematic (displacement, speed and acceleration of
      segments) and kinetic parameters during the four successive stages of gait
      (posture, initiation, rhythmic gait and return to the initial posture) provides
      an understanding of neurological gait disorders. In particular the relationship
      between the center of pressure and the center of gravity is used to analyze
      infraclinical gait abnormalities. NEW AND SOPHISTICATED INVESTIGATIONS METHODS
      ARE AVAILABLE: The optoelectronic system provides a tridimensional analysis of
      movement and can be combined with forceplate and electromyographic recordings.
      These methods constitute an interesting contribution to the clinical analysis of
      gait. CLASSIFICATION: This is established according to clinical data and the
      positionment of the lesion among the structures of the nervous system. The
      physiopathological approach is then specified taking into account the lesions of
      the muscular, skeletal and nervous structures.

PMID- 11285785
TI  - [Gait disorders in Parkinson disease. Clinical description, analysis of posture,
      initiation of stabilized gait].
AB  - A WELL INFORMED DESCRIPTION: The parkinsonian posture is generally described as a
      stooped one. At the beginning of the disease, the gait troubles remain moderate;
      gradually the gait is composed of small steps without a wide base; the patient
      tends to run after his centre of gravity by accelerating the step (festination
      phenomenon). Difficulties occurs for starting up (delay of gait initiation), for
      about-turn or for clearing obstacles. Kinetic jammings and standing around
      (freezing) can last several seconds and be responsible for falls. POSTURAL
      INSTABILITY, A MAJOR SYMPTOM IN PARKINSON'S DISEASE: This symptom is little
      improved by therapies and is responsible for serious disability. Postural
      instability induces a disequilibrium and is partially due to a simultaneous
      antagonist muscles contraction and to the impossibility of modifying postural
      responses to changing support conditions. The passive viscoelastic properties of
      muscles and tendons constitute a first line of defence against the disequilibrium
      and contribute to postural stability in the case of medium disturbances.
      Automatic and voluntary postural responses which come into play in the case of
      major disturbances can also be impaired (delay or defect of the responses). GAIT
      INITIATION FAILURE ARE FREQUENT: They result from an increase of the postural
      phase and a decrease of the propulsion forces, depending on a deficit of the
      postural anticipation mechanisms and also the sequential organization and the
      integration of two different motor programs, postural and locomotor. They can be
      controlled partially with sensory stimuli, notably visual inputs. DATA CONCERNING
      STABILIZED WALKING AND ITS PATHOPHYSIOLOGY REMAINS TO BE CLARIFIED: Spatial and
      temporal parameters are impaired: speed, step length and swing phase are reduced,
      while cadence increases to compensate these troubles. These modifications are the
      consequence of an incapacity to produce internal marks to generate regular steps.
      When the parkinsonian patient is supplied with external marks, these parameters
      can be normalized. From a pathophysiological point of view, gait disorders could
      result from defective central integration of proprioceptive information during
      movement within the basal ganglia, associated with a visual perceptive deficit
      linked with a retinal dopaminergic cells dysfunction and finally from an
      impairment of the proprioceptive feedback of the load receptors in the leg
      extensor muscles.

PMID- 11285786
TI  - [Gait disorders in Parkinson disease. Gait freezing and falls: therapeutic
      management].
AB  - GAIT ARRESTS: They affect the evolution of the disease. This freezing phenomenon
      which induces falls sometimes constitutes an initial sign. Like the gait
      initiation failure, freezing can be controlled by sensory stimulation, notably
      visual inputs, but also by more sustained attention. FALLS ARE MAINLY CONNECTED
      WITH BOTH POSTURAL INSTABILITY AND RIGIDITY: They are poorly influenced by
      dopaminergic therapies. The progressive decrease of step width represents a main
      factor in their occurrence. PRECOCITY OF GAIT DISORDERS IS UNUSUAL IN PARKINSON'S
      DISEASE: Other parkinsonian syndromes such as progressive supranuclear palsy,
      multiple system atrophy and vascular parkinsonian syndrome must then be evoked.
      Their association with a cognitive impairment and abnormal sphincter behaviour
      infers a diagnosis of normal pressure hydrocephalus. GAIT IMPROVES WITH L-DOPA
      THERAPY: Speed, step length and duration of the swing phase are increased without
      change of cadence. Progressive loss of L-dopa efficiency on gait and postural
      stability contrasts with the persistent effect on tremor, rigidity and
      bradykinesia; a functional abnormality of nondopaminergic systems can explain
      these symptoms. In the following stages, gait troubles increased by motor
      fluctuations and abnormal involuntary movements are less controlled by L-dopa
      therapy. PHYSICAL THERAPY PLAYS A MAJOR ROLE IN THERAPEUTIC MANAGEMENT: An
      individual or collective rehabilitation project must be established according to
      the stage of evolution; the exercises aim to protect postural control and
      coordination. Visual or sound rhythmic inputs can be employed in the case of gait
      initiation failure. THE EFFECTS OF FUNCTIONAL NEUROSURGERY ARE IN THE COURSE OF
      EVALUATION: Thermolesion and chronic electrical stimulation of deep brain
      structures have opposite effects on gait troubles. Bilateral thalamotomy or
      pallidotomy are sometimes a source of disequilibrium. Chronic thalamic
      stimulation does not induce either benefits or adverse effects. On the other
      hand, stimulation of the internal pallidum improves gait kinematic parameters;
      improved postural adjustments have also been reported. The effect of subthalamic
      nucleus stimulation is comparable to that of L-dopa, however the long-term effect
      remains to be evaluated.

PMID- 11285787
TI  - Sickness absence and rehabilitation: what hope of change?

PMID- 11285788
TI  - Neurological complications of cervical spine manipulation.
AB  - To obtain preliminary data on neurological complications of spinal manipulation
      in the UK all members of the Association of British Neurologists were asked to
      report cases referred to them of neurological complications occurring within 24
      hours of cervical spine manipulation over a 12-month period. The response rate
      was 74%. 24 respondents reported at least one case each, contributing to a total
      of about 35 cases. These included 7 cases of stroke in brainstem territory (4
      with confirmation of vertebral artery dissection), 2 cases of stroke in carotid
      territory and 1 case of acute subdural haematoma. There were 3 cases of
      myelopathy and 3 of cervical radiculopathy. Concern about neurological
      complications following cervical spine manipulation appears to be justified. A
      large long-term prospective study is required to determine the scale of the
      hazard.

PMID- 11285789
TI  - Health consequences of global climate change.

PMID- 11285790
TI  - Severe asthma phenotypes: the case for more specificity.

PMID- 11285791
TI  - BCG immunotherapy for superficial bladder cancer.

PMID- 11285792
TI  - Reptile-related salmonellosis.

PMID- 11285793
TI  - Diabetic retinal screening in the UK.

PMID- 11285794
TI  - A brief history of pancreatitis.

PMID- 11285795
TI  - Silicone in the sputum after rupture of a calf implant.

PMID- 11285796
TI  - Seven recurrences of spinal inflammation.

PMID- 11285797
TI  - Herpetic trigeminal trophic syndrome in an infant.

PMID- 11285798
TI  - Metastatic in-situ perianal Paget's disease.

PMID- 11285799
TI  - Orthopaedic manifestations of congenital insensitivity to pain.

PMID- 11285800
TI  - Psychosis in hypomelanosis of Ito.

PMID- 11285801
TI  - John Misaubin, Hogarth's quack: a case for rehabilitation.

PMID- 11285802
TI  - Does psychiatry stigmatize?

PMID- 11285803
TI  - Instrumental psychosis (Svejkosis).

PMID- 11285804
TI  - Instrumental psychosis (Svejkosis).

PMID- 11285805
TI  - Instrumental psychosis (Svejkosis).

PMID- 11285806
TI  - Instrumental psychosis (Svejkosis).

PMID- 11285807
TI  - Why doctors get angry in Crown courts.

PMID- 11285808
TI  - Reversible dementia in Paget's disease.

PMID- 11285809
TI  - Analyzing developmental trajectories of distinct but related behaviors: a group
      based method.
AB  - This article presents a group-based method to jointly estimate developmental
      trajectories of 2 distinct but theoretically related measurement series. The
      method will aid the analysis of comorbidity and heterotypic continuity. Three key
      outputs of the model are (a) for both measurement series, the form of the
      trajectory of distinctive subpopulations; (b) the probability of membership in
      each such trajectory group; and (c) the joint probability of membership in
      trajectory groups across behaviors. This final output offers 2 novel features.
      First, the joint probabilities can characterize the linkage in the developmental
      course of distinct but related behaviors. Second, the joint probabilities can
      measure differences within the population in the magnitude of this linkage. Two
      examples are presented to illustrate the application of the method.

PMID- 11285810
TI  - Empirical and hermeneutic approaches to phenomenological research in psychology:
      a comparison.
AB  - Empirical phenomenology and hermeneutic phenomenology, the 2 most common
      approaches to phenomenological research in psychology, are described, and their
      similarities and differences examined. A specific method associated with each
      form of phenomenological inquiry was used to analyze an interview transcript of a
      woman's experience of work-family role conflict. A considerable degree of
      similarity was found in the resulting descriptions. It is argued that such
      convergence in analyses is due to the human capacities of reflection and
      intuition and the presence of intersubjective meanings. The similarity in the
      analyses is also encouraging about researchers' ability to reveal meaning despite
      the use of different methods and the difficulties associated with interpreting
      meaning.

PMID- 11285811
TI  - Do logistic regression and signal detection identify different subgroups at risk?
      Implications for the design of tailored interventions.
AB  - Identifying subgroups of high-risk individuals can lead to the development of
      tailored interventions for those subgroups. This study compared two multivariate
      statistical methods (logistic regression and signal detection) and evaluated
      their ability to identify subgroups at risk. The methods identified similar risk
      predictors and had similar predictive accuracy in exploratory and validation
      samples. However, the 2 methods did not classify individuals into the same
      subgroups. Within subgroups, logistic regression identified individuals that were
      homogeneous in outcome but heterogeneous in risk predictors. In contrast, signal
      detection identified individuals that were homogeneous in both outcome and risk
      predictors. Because of the ability to identify homogeneous subgroups, signal
      detection may be more useful than logistic regression for designing distinct
      tailored interventions for subgroups of high-risk individuals.

PMID- 11285812
TI  - Hierarchical modeling of paired comparison data.
AB  - The method of paired comparisons belongs to a small group of techniques that
      provide explicit information about the consistency of individual and aggregated
      choices. This article investigates the link between the individual- and group
      level judgments by extending R. D. Luce's (1959) model, which was originally
      developed for individual choice behavior, to a mixed-effects paired comparison
      model. It is shown that standard multilevel software for binary data can be used
      to estimate the model. The interpretation of the paired comparison parameters and
      statistical model tests are discussed in detail. An extensive analysis of an
      experimental study illustrates the usefulness of a hierarchical approach in
      modeling multiple pairwise judgments.

PMID- 11285813
TI  - A comparison of factor scores under conditions of factor obliquity.
AB  - Six different methods of computing factor scores were investigated in a
      simulation study. Population scores created from oblique factor patterns selected
      from the psychological literature served as the bases for the simulations, and
      the stability of the different methods was assessed through cross-validation in a
      subject-sampling model. Results from 5 evaluative criteria indicated that a
      simplified, unit-weighting procedure based on the factor score coefficients was
      generally superior to several unit-weighting procedures based on the pattern or
      structure coefficients. This simplified method of computing factor scores also
      compared favorably with an exact-weighting scheme based on the full factor score
      coefficient matrix. Results are discussed with regard to their potential impact
      on current practice, and several recommendations are offered.

PMID- 11285815
TI  - Working knowledge. Touch screens.

PMID- 11285814
TI  - Three-way component analysis: principles and illustrative application.
AB  - Three-way component analysis techniques are designed for descriptive analysis of
      3-way data, for example, when data are collected on individuals, in different
      settings, and on different measures. Such techniques summarize all information in
      a 3-way data set by summarizing, for each way of the 3-way data set, the
      associated entities through a few components and describing the relations between
      these components. In this article, 3-mode principal components analysis is
      described at an elementary level. Guidance is given concerning the choices to be
      made in each step of the process of analyzing 3-way data by this technique. The
      complete process is illustrated with a detailed description of the analysis of an
      empirical 3-way data set.

PMID- 11285816
TI  - Getting more from Moore's.

PMID- 11285817
TI  - Code of the code.

PMID- 11285818
TI  - Colorful pebbles and Darwin's dictum.

PMID- 11285819
TI  - Whose blood is it, anyway?

PMID- 11285820
TI  - Seeds of concern.

PMID- 11285821
TI  - The risks on the table.

PMID- 11285822
TI  - Does the world need GM foods? Yes. Interview by Sasha Nemecek.

PMID- 11285823
TI  - Does the world need GM foods? No. Interview by Sasha Nemecek.

PMID- 11285824
TI  - Virtually there.

PMID- 11285825
TI  - Life's rocky start.

PMID- 11285826
TI  - The fury of space storms.

PMID- 11285827
TI  - Violent pride.

PMID- 11285829
TI  - [Study on alkaline hydrolysis of polyglutamate for de-esterification].
AB  - This paper reports the alkaline hydrolysis of poly(methyl glutamate), poly
      (benzyl glutamate) and copoly(methyl glutamate-benzyl glutamate-glutamic acid)
      for de-esterification. The results showed that in this process of alkaline
      hydrolysis the demethylation of poly(methyl glutamate) was faster, but
      debenzylation of poly(benzyl glutamate) was hardly processed. An increase in the
      methyl glutamate content of starting copolymers, in the alkaline concentration
      and the time of alkaline hydrolysis, and a decrease in the film thickness, would
      lead to a raise in the degree of alkaline hydrolysis, that is, an increase of the
      glutamic acid segment content in product of alkaline hydrolysis.

PMID- 11285828
TI  - [Evaluation of performance and blood compatibility of polyethersulfone hollow
      fiber plasma separator].
AB  - In this study, we evaluated the performance and blood compatibility of
      polyethersulfone hollow fiber membrane plasma separator by animal experiment.
      Hemolysis did not occur under the usual conditions of plasma separation. The
      sieving coefficients of total protein, albumin and globulin were over 95%, and
      about 60% of total plasma were extracted from the whole blood. White blood cells,
      platelets, fibrinogen, and coagulation factors were decreased during the early
      stage of plasma separation and appeared to be within acceptable ranges for
      clinical use.

PMID- 11285830
TI  - [In vitro testing of a new implantable ventricular assist rotary pump made in
      China].
AB  - We have measured the hemodynamic properties of the rotary pump in order to give
      directions for use in animal test and even in clinical application. In our
      mocking circulation circuit, under definite preload, the inner diameter of inlet
      and outlet cannulae and the afterload have been changed for measuring the
      pressure of input and output of the pump and the pump flowing rate when it runs
      under 75% maxim working condition. The results demonstrate that with the cannulae
      of inner diameter of 8 mm as drainage, the pump provides 5.32 L/min of output
      against a mean afterload of average 60 mmHg(1 mmHg = 0.133 kPa) with a filling
      pressure of 10 mmHg. With the cannulae usually used in clinical setting, the
      flowing rates are more than 1.5 L/min against a mean afterload of 90 mmHg, and
      all output pressure of the pump is higher than 120 mmHg. In conclusion, the
      volume of the rotary pump is small, the needed power is low, and the hemodynamic
      parameters are suitable for animal test and even for clinical use.

PMID- 11285831
TI  - [Analysis of dynamic stress for human skull-brain under impact loading with
      acceleration and deceleration].
AB  - In this paper, we measure and analyze the changes of dynamic stress in human
      skull-brain under impact loading. By applying the frequency responding function
      and coherence function produced by the pressure of impact wave at each point on
      skull, and by use of the viewpoint of biomechanics, we further research into
      brain injuries and have got some data which cannot be obtained in clinical
      setting.

PMID- 11285832
TI  - [One-dimensional impact dynamic response of cancellous bone].
AB  - In this paper a one-dimensional dynamic response of cancellous bone to impact
      loading is investigated. It is demonstrated, based on the studies with scanning
      electron microscope, cancellous bone could be viewed as a cellular solid
      consisting of an interconnected skeleton filled with medulla. A two-phase
      poroelastic model is introduced to describe the cancellous bone, in which the
      tissue(material) densities of the skeleton and medulla are assumed to be
      unchangeable while the corresponding apparent densities are changeable due to the
      change of volume fraction, the governing equations are derived for the case of a
      linear poroelastic solid skeleton saturated with an inviscid medulla. Under the
      impact loading, responses of the skeleton displacement and stress as well as the
      medullary pressure are obtained with the use of Laplace transform technique. The
      computational result shows that the cancellous bone is provided with certain
      features similar to those appearing in viscoelastic solids, which means that the
      responses do not only depend on time, but furthermore depend on previous loading
      history. It is worth paying attention to the result that the medullary pressure
      can be negative. This point is due to the recovery of the skeleton after
      unloading whereas the medulla is not squeezed out but absorbed into the pores by
      suction.

PMID- 11285833
TI  - [Measure of vibration protection effect of driver's corset and analysis of its
      biomechanical effect].
AB  - The purpose of this study was to evaluate the vibration protection and
      biomechanical effect of driver's corset. The frequencies of vertfical and
      horizontal vibrations were measured at low back of driver. The vehicle driven was
      ISUZU truck (loading capacity 8 tons). Vibration of the driver's lumbar back was
      measured real time with wear corset and without wear corset when the truck loaded
      with 6 tons was driven at the spead of ten, thirty and sixty kilometers an hour
      on the asphalt road. The results showed: 1. Vibration frequencies at driver's low
      back was under 10 Hz. It is a low frequency vibration. 2. The value of vertical
      vibration was higher than the value of horizontal (back and forth) vibration. 3.
      The vibration value of wear corset was higher than un-wear corset. These indicate
      the driver's corset is effective for protecting lumbar spine by means of change
      in the biomechanical characteristics and the resonace requencies of lumbar spine.
      So the driver's corset is one of the good methods for preventing the back pain of
      drivers.

PMID- 11285834
TI  - [A biomechanical model of lymph formation].
AB  - In this study we analysed the interactions between initial lymphatic and
      interstitium, examined the procedure of lymph formation, developed the
      interaction theory for lymph formation, and showed that not only interstitial
      fluid prssure but also normal stress of interstitial solid phase should be
      considered and that lymph flow rate is greatly affected by interstitial porosity.

PMID- 11285835
TI  - [Bridging artery defect with autogenous vein under required anastomosing tension-
      a theoretical analysis based on related biomechanical evidence].
AB  - This study was aimed to establish a rabbit model of bridging artery defect with
      autogenous vein under required tension by selecting and appropriate length of
      graft. The uniaxial loading test in longitudinal direction was performed using 14
      femoral arteries and 14 femoral veins. The tension(F)-strain(lambda) curve was
      measured and the exponential form F = m1 * [em2(lambda-1)-1] was employed to fit
      the curve. The results showed that with the range of 35.0 mm actual isolated
      length (AIL), the exponential form Fa = 0.22[e5.75(lambda a-1)-1] and Fv = 6.15 *
      10(-3) [e7.89(lambda v-1)-1] could well fit the experimental data of rabbit's
      femoral artery and vein respectively. Therefore to make sure the required
      anastomosing tension F, the length of vein graft(LVG) should qualify the
      equation: (LVG/1.64) x lambda v + [(AIL - ADL)/1.58] x lambda a = AIL while 1.65
      and 1.58 are the physiological stretch ratio of artery and vein, lambda v and
      lambda a stand for that of vein and artery under tension F, respectively.

PMID- 11285836
TI  - [Surface EMG signal classification using wavelet transform].
AB  - A Surface EMG signal classification method based on wavelet transform is
      presented in this paper. To utilize the nonstationary character of the EMG
      signals, dyadic wavelet transform is employed to obtain the signals' time
      frequency representation. Singular value decomposition(SVD) is then used to
      extract feature vector for pattern classification. This motion classifier can
      successfully identify four types of forearm movement: hand grasp, hand extension,
      forearm pronation and forearm supination. Experimental result shows that this
      method has a great potential in the practical application of prothesis control.

PMID- 11285837
TI  - [Improvement of pulse waveform detection with autoregressive model in blood
      oxygen saturation measurement].
AB  - Blood oxygen saturation is an important physiological parameter of human body.
      The accurate measurement of it is important to both physiological research and
      medical application. Dual-wavelength method is widely adopted in nonivasive
      detection of blood oxygen saturation. In this method, the calculation of blood
      oxygen saturation is based on the identification of pulse waveform and the
      extraction of peak characteristic values. But the pulse waveform obtained from
      this method merely has distinctive features such as the QRS complexes in ECG, so
      the ratio of correct detection of pulse waveform is always low. An autoregressive
      model of heart-beat intervals is developed. The output of the differential method
      is compared with that of the AR model so as to distinguish the false or missing
      detection. The ratio of correct detection is improved by the use of this method.

PMID- 11285838
TI  - [3-D motion detection system of human hand].
AB  - This paper presents a 3-D motion detection system of human hand, which is based
      on ordinary video cameras. It includes two pickup cameras, calibration frame and
      landmark identification system. The DLT algorithm is used to reconstruct the 3-D
      motion trajectory of human hand. The paper also presents the principle of the
      system and some detection experiments, and the results showed the good
      performance of the system. It offers a useful tool for the human hand motion
      quality analysis and evaluation.

PMID- 11285839
TI  - [Computerized surgical simulation with 3D reconstruction of upper limbs].
AB  - This paper reports our study on how to realize computerized surgical simulation
      through reconstructing 3D anatomy of upper limbs. CT images and serial sections
      of upper limbs were matched to reconstruct 3D images. We compiled the computer
      programs of 3D reconstruction and surgical simulation with borland C++ computer
      language, and built 3D digital model of anatomic structure of upper limbs. The
      results showed that all structures reconstructed could be displayed alone, in any
      group or totally. While operating, we could choose one of three segments of the
      upper limbs model and operate on any parts and in any direction. The surgical
      simulation system could be used to design operative schemes, choose the best
      operative paths, and teach the processes of operations and anatomy. It could run
      in 586-personal computers.

PMID- 11285840
TI  - [An experimental study of human tracheal epithelial transfer of human neutrophil
      defensin gene].
AB  - This study was amied at the possibility of production of the human neutrophil
      defensin in human tracheal epithelial cells when transfected with it's gene by
      using liposome. The plasmid vector carrying the human neutrophil defensin HNP1
      (human Neutrophil Peptide-1) gene was used to transfect the human tracheal
      epithelial cells cultured in serum-free complement medium by lipofection reagent.
      Antiserum of HNP1 was prepared and used for the immunocytochemistry staining to
      detect expression of HNP1 gene in human tracheal epithelial cells. The result
      showed that recombinant eukaryote expression plasmid-pBabe-Neo-HNP1 could be
      transducted into human tracheal epithelial cells by liposomal transfection
      method. Transducted cells showed strong positive staining for HNP by
      immunohistochemistry assay. It was suggested that HNP1 gene could be productively
      transduced into human tracheal epithelial cells and expressed by using liposome.
      Antibiotic peptide gene might be used for gene therapy of respiratory infections.

PMID- 11285841
TI  - [Study on human sensitivity of extremely low frequency electromagnetic field].
AB  - In this paper, the action potential through membrane is calculated and analyzed
      based on the crowd model. The analysis shows that membrane action potential will
      be amplified if the coefficient k1, k2 meet some certain conditions. This effect
      could cause ionic current increase and even results in electroporation, membrane
      broken. The result can be used to explain some athermal bioeffect of living
      beings in weak EMF and is helpful for biomedicine application.

PMID- 11285842
TI  - [The software method for cross-talk correction in ultrasound Doppler blood flow
      measurement].
AB  - The cross-talk in ultrasound Doppler measurement will lead to wrong decision in
      clinical diagnosis. In order to reduce cross-talk, the software method for cross
      talk correction was presented in this paper. The cross-talk error was obtained by
      signal correlation technique first, the correction for blood flow signal was then
      realized. Simulation results prove that the software method can be used to
      correct cross-talk error well. It is a promising method.

PMID- 11285843
TI  - [An analysis of precision and accuracy of the phonocardiogram exercise test].
AB  - Phonocardiogram exercise testing (PCGET) is a recently developed method to
      evaluate cardiac contractility and the cardiac reserve of patients with heart
      disease and of healthy subjects. In order to test the reliability of PCGET
      method, the present author conducted a study on its precision and accuracy.
      Thirty volunteers underwent PCGET. When different examiners measured the S1
      amplitude in the same cardiac cycle of the same subject, the data obtained by
      examiner A were: x +/- s = 5.05 +/- 0.0451; the data obtained by examiner B were:
      x +/- s = 4.95 +/- 0.0346, F = 1.699, P > 0.05. When different examiners measured
      the same cardiac cycle of the same subject, the data obtained by examiner A were:
      x +/- s = 0.789 +/- 0.0018; the data obtained by examiner B were: x +/- s = 0.787
      +/- 0.0017, F = 1.167, P > 0.05. The results suggest that PCGET is a nonivasive,
      convenient, and inexpensive technique to quantitatively evaluate cardiac reserve
      for abnormal or normal persons.

PMID- 11285844
TI  - [The development and application of a minitype multifunctional bio-impactor].
AB  - This study was aimed to develop a device that can be used for gas percussion,
      rigid impact, cell injury and simple estimation of the condition of injury. The
      device has been developed with the use of aerodynamical principle, measuring
      technique for feeble signal, and integration of machine-electricity. The gas
      percussion, rigid impact, and cell injury can be produced by altering impact tip.
      It was examined in the experimental researches of eye, brain, lung and cell
      injury; the parameters of causing injury could be controlled and on-line tested
      by the computer. The neurological states of pre- and post-injury were evaluated
      with the device. The results of animal experiments showed that mild, moderate and
      severe injury models were produced by gas pressure respectively. The pressure was
      400, 600, 700 kPa for rats brain gas percussion injury, 600, 800, 1000 kPa for
      rabbits' retinal contusion, 300, 450, 600 kPa for rats' lung rigid impact injury,
      and 100, 150, 200 kPa for cultured cells' injury. In conclusion, the device is
      simple and easy to use for making controllable injury models, in which different
      parts and levels of injuries on different minitype animals can be reproduced.

PMID- 11285845
TI  - [Study of an in-vivo and real-time method to measure blood viscosity].
AB  - The traditional methods to measure blood viscosity are out-line. They have the
      disadvantages of long measurement time, many disturbance factors during
      measurement, the damage to blood sample, and etc. So rapidity, accuracy and
      repeatability are not satisfactory. A new method to measure blood viscosity is
      proposed in this paper, which uses needle instead of capillary and can measure
      blood viscosity during collecting blood. Owing to the advantages of small amount
      of blood sample, rapidity and repeatability, the new method is of value for
      clinical application.

PMID- 11285846
TI  - [Recognition of multiple information of human auricular points by linear model].
AB  - The three variables of the electric characteristic of human auricular points can
      be regarded as observed targets that reflect the physiologic or pathologic
      changes. Medical principle design follows the theory of the channels and
      collaterals and the viscera-state doctrine of traditional Chinese medicine and
      that of the pattern recognition. The linear integration model can be established
      by drawing the characteristic variables of the correlation groups of the
      auricular points and applying the multi-variable normalization. With this model,
      the recognition of the three variations of the auricular points can be of use for
      differential diagnosis. In this paper, the test to identify the cases of Upper
      Digestive tract achieves good result. This research, based on the integration of
      modern science with traditional Chinese medicine, provides a method for building
      the specialist system of the auricular point diagnosis, and probably has some
      prospect in clinical application.

PMID- 11285847
TI  - [Photochemical immobilization--a new approach to surface modification of medical
      polymer materials].
AB  - The present paper reviews the approach of surface modification of medical polymer
      materials-photochemical immobilization. The approach is dramatically different
      from any other surface modification process available for medical materials. The
      topics include the principle of photochemical immobilization, the fundamental
      classification photoreactive groups and the typical applications of photochemical
      surface modification.

PMID- 11285848
TI  - [Biomechanics of temporomandibular joint].
AB  - Temporomandibular joint (TMJ) is one of the most intricate and complicate loading
      joints in the human body. Articular cartilage is characteristic of low
      infiltrative, porous viscoelastic material. In physiological condition, there is
      a stress-absorbing architecture system in the TMJ cartilage, which consists of
      collagen-proteoglycan-water gel network. TMJ disc is a specific connective tissue
      as stress concentration absorber between condyle and articular fossa, but it does
      not belong to fibrocartilage. Retrodiscal tissue has high compliance of which the
      role is to play volume-compensating mechanism in joint movement. Lateral wall is
      a complexed structure out of ligament and capsule with weak tensile strength and
      tensile rigidity. Therefore, prolonged oral parafunction will result in joint
      fatigue and failure.

PMID- 11285849
TI  - [Discussion on the engineering problems in oral implantology].
AB  - The engineering problems in oral implantology are discussed in this paper. The
      problems discussed include the comparison among implants of different shapes, the
      influence of lengths and diameters of implants on the biomechanics properties of
      interface, the influence of pitches and tooth angles of threaded implants on the
      biomechanics properties of interface, the influence of methods of surface
      treatment and surface topography of implants on the biomechanics properties of
      interface, the characteristics of implant denture design, the application of
      picture treatment technology and solid model manufacturing technology in implant
      denture reconstruction.

PMID- 11285850
TI  - [Mathematical models of cardiac myocytes and their applications in simulating
      electrophysiological activities].
AB  - Based on historical developments, the mathematical models of cardiac myocytes and
      their applications in simulating electrophysiological activities are summed up.

PMID- 11285851
TI  - [Automated analysis technology of electrocardiograms].
AB  - Study of detection and analysis methods for electrocardiograms(ECGs) has been
      developed for more a decade. But it is still existing some problems because of
      patient idiosyncrasy. The automated analysis of ECGs was simply summarized at the
      present for existing problems and with possible way to solve those troubles. We
      have reviewed preprocessing methods of waveform detection of ECGs and diagnosis
      techniques of arrhythmia.

PMID- 11285852
TI  - [Progress in researches on anti-tumor agent L-asparaginase for treatment of
      leukemia].
AB  - L-asparaginase is a very effective anti-tumor agent. To take the most advantage
      of enzyme treatment method, the natural L-asparaginase could be chemically
      modified, entrapped or immobilized into/onto other carriers. The extracorporeal
      shunt system with immobilized enzyme reactor deserves to receive special
      attention. It provides an entirely new idea for leukemia treatment and is proved
      to be very prospective in the future leukemia cure.

PMID- 11285853
TI  - [Preparation of biological bone carrier].
AB  - A series of studies on biological bone carrier (BBC), including preparation
      methods, components analysis, animal implantation test, biomechanical strength,
      ultrastructure, cross antigenicity and clinical application are reported in this
      article. Comprehensive process was adopted to reduce the antigen of BBC. As a
      substitute for bone, BBC has the following merits: (1) good biocompatibility; (2)
      suitable mechanical strength; (3) natural porous structure and porosity; (4)
      absorbability and replaceability in host; (5) unlimited sources, ready
      availability and simplicity in process and storage; (6) both functions of
      osteoconductability and osteoinductability can be developed after BBC combined
      with BMP.

PMID- 11285854
TI  - [Analysis of the design principle and mechanics nature of adjustable semi
      circular planum external fixator].
AB  - This thesis presents our studies of an adjustable semi-circular planum external
      fixator and offers a relatively detailed introduction and analysis of the
      structure principle and mechanics nature. Because dual-direction joining pole
      with active joints was used, by adjusting the length of each pole, it can not
      only make the two semi-circular steel plates more parallely along the axis line
      to stabilize the fracture and lengthen the extremity, but it also can change the
      planum angle of the steel plate, and thus achieve the effect of orthopaedic
      function.

PMID- 11285855
TI  - [The research and manufacture of the pneumatic left ventricular assist pump].
AB  - The manufacturing methods and testing results of the pneumatic left ventricular
      assist pump(L-Y pump) are introduced in this paper. The results demonstrate that
      L-Y pump is reliable, biocompatible and in keeping with the clinical
      requirements.

PMID- 11285856
TI  - [The development of a computer-based visual field analyzer].
AB  - Visual field is one of the important visual functions; it is the extent of the
      visual field defect that can be employed in judging whether the visual function
      is impaired. The rapid achievements in computer technologies do provide an
      impulse for improvement of visual field detection, making possible the automatic,
      rapid, accurate, detailed and large-scaled visual field detection. This paper
      gives a thorough description about development of the visual field analyzer,
      model TEC-2A, which is based on PC windows platform, Visual Basic software
      developing tool, ISA peripheral circuits, standard Goldmann visual field half
      ball and standard stimulus.

PMID- 11285857
TI  - [A study of sleep apnea monitoring method and instrument].
AB  - In this paper the fundamental principle and great significance of sleep apnea
      monitoring are introduced, and the status quo of this field at home and abroad is
      described. Several kinds of methods for sleep apnea monitorin are analyzed, and
      on this basis the authors have developed a cheap and portable sleep apnea
      monitoring instrument. Experiment results demonstrate that the instrument is of
      convenience, high accuracy and good performance.

PMID- 11285858
TI  - [Analysis of the construction of creature valves frame].
AB  - This paper analyses the construction of the creature valves frame according as
      the theory of Membrane in order to enable the creature valves to take the place
      of cardial valves of human being. It provides solid theoretical foundations for
      building the mathematical model and computer-aided design of the creature valves
      frame.

PMID- 11285859
TI  - [Determination of fructose-1,6-diphosphate with aldolase-DNPH by the colorimetric
      method].
AB  - This paper presents a modified method of enzymatic assay for Fructose-1,6
      diphosphate(FDP). FDP is split to dihydroxyacetone phosphate (DAP) and
      glyceraldehyde-3-phosphate (GAP) by the action of aldolase. DAP is hydrolyzed at
      room temperature to free triose. Under alkaline conditions, the free triose is
      reacted with 2,4-dinitrophenylhydrazine (DNPH), yielding a 2,4
      dinitrophenylhydrazine derivative which dissolve in alkali forming a purple color
      mixture, with maximum absorption at 540.nm. It is proportional to the contents of
      FDP. Because the method depends on the colorimetric determination of triose
      formed from fructose-1,6-diphosphate only by aldolase, glycerophosphate
      dehydrogenase/triosephosphate isomerase (GDH/TIM) and reduced nicotinamide
      adenine dinucleotide (NADH) which usually applied in multienzymatic method, are
      omitted in the modified method. The method is specific, convenient and accuracy
      for the determination of FDP.

PMID- 11285860
TI  - [Skeletal dysplasia and osteoporosis due to inadequate athletic].
AB  - Athletic load is an important factor that has an influence on the growth,
      development and mature of skeleton. In patients who had the functional disorder
      of hip joint resulting from hip diseases during their teen-ages, skeletal
      dysplasia and osteoporosis would occur. The present paper reported 30 cases of
      unilateral hip disorder. The patients were 20 men and 10 women whose age ranged
      from 2 to 20 years. The course of disease lasted 2 to 49 years. Their primary
      diseases included suppurant hip arthritis (16 cases), tuberculous arthritis of
      hip (10 cases), and others (4 cases). The follow-up study revealed fixed hip
      joint in 18 cases, positive Thomas sign in 22 cases, limited motion of hip joint
      in 12 cases, and unequal length of lower extremities in 25 cases; at the same
      time X-ray films showed ankylosis of hip at normal position in 10 patients,
      dislocation with ankylosis of hip in 13 patients, arthritic disorder of hip in 7
      patients, skeletal dysplacia of ischium and pubis in 18 patients, and skeletal
      dysplasia of femur in 22 patients. All patients had osteoporosis. A discussion
      about the basic mechanism for skeletal dysplasia and osteoporosis following
      inadequate athletic load is presented. We believe that the skeletal dysplasia and
      osteoporosis in our group were caused by the diseases that led to inadequate
      athletic load. Therefore it is important to provide a thorough treatment and help
      the patients to their strength to be loaded in time.

PMID- 11285861
TI  - To solve a deadly shortage: economic incentives for human organ donation.
AB  - In this article Dr. Harris and attorney Alcorn propose the establishment of a
      governmentally regulated, posthumous organ market, with economic incentives for
      the donors, in order to increase the supply of transplantable organs. The authors
      review transplant technology, provide a short history of donation and sale of
      organs, tissues, and cells, discuss the various legislative approaches that have
      been made to increase the supply of organs, and analyze the problems with the
      open market approach. They conclude with a proposal for a regulated posthumous
      organ market.

PMID- 11285862
TI  - Countertransference and assisted suicide.

PMID- 11285863
TI  - Abortion, information & the law: what every doctor needs to know.
AB  - 1. Before commencing any treatment, doctors must inform patients of all material
      risks of the treatment (Rogers v. Whitaker, 1992). 2. It is not up to the
      professional judgment of doctors to decide how much information to give to
      patients (Rogers v. Whitaker, 1992). 3. The same duty to inform applies to
      abortion ("Ellen's Case," 1998). 4. GPs and counsellors who refer for abortion
      also have a legal duty to inform women of risks, because everyone who gives
      specialized or professional advice may be sued for negligence if that advice is
      given without due care (Evatt's Care, 1969). 5. Doctors have been inadequately
      informed on the medical risks of abortion, by writers seeking to present abortion
      as a risk-free procedure. 6. Abortion may increase the risk of cancer. 7.
      Abortion carries risks of injury and illness. 8. Abortion caries risks of future
      reproduction. 9. Abortion may have adverse psychological and psychiatric
      sequelae. In some women, these sequelae are severe and intractable, and may occur
      irrespective of a woman's personal attitudes towards abortion (Melinda Tankard
      Reist, Giving Sorrow Words: Women's Stories of Grief After Abortion, Sydney,
      Duffy & Snellgrove, 2000). 10. Women still die in Australia from abortion. 11. It
      has not been proved that pregnancy and delivery are more dangerous than abortion.
      12. The risks of mortality and morbidity in carrying a pregnancy to term are
      often exaggerated, in an effort to make abortion appear safer. 13. Doctors are
      not required to refer for abortion. On the other hand, doctors do have a duty to
      inform themselves of the professional competence of any practitioner to whom they
      refer any patient for any procedure. Doctors who are referring for abortion can
      avoid legal jeopardy by informing women fully of the risks, and by keeping very
      comprehensive records of the information they have given. Alternatively, doctors
      can avoid legal liability by declining to refer for abortion. There are
      compelling medical reasons for treating abortion as a social, non-therapeutic,
      potentially harmful procedure with which conscientious doctors would choose not
      to involve themselves.

PMID- 11285864
TI  - Legalization of euthanasia in the Netherlands.

PMID- 11285865
TI  - Should color vision screening yield a black or white answer?

PMID- 11285866
TI  - Screening for color vision testing should be black or white, but screening should
      not constitute the final answer.

PMID- 11285867
TI  - Silica, silicosis, and lung cancer.

PMID- 11285868
TI  - Workforce health problems: present--and now accounted for.

PMID- 11285869
TI  - The effects of chronic medical conditions on work loss and work cutback.
AB  - Although work performance has become an important outcome in cost-of-illness
      studies, little is known about the comparative effects of different commonly
      occurring chronic conditions on work impairment in general population samples.
      Such data are presented here from a large-scale nationally representative general
      population survey. The data are from the MacArthur Foundation Midlife Development
      in the United States (MIDUS) survey, a nationally representative telephone-mail
      survey of 3032 respondents in the age range of 25 to 74 years. The 2074 survey
      respondents in the age range of 25 to 54 years are the focus of the current
      report. The data collection included a chronic-conditions checklist and questions
      about how many days out of the past 30 each respondent was either totally unable
      to work or perform normal activities because of health problems (work-loss days)
      or had to cut back on these activities because of health problems (work-cutback
      days). Regression analysis was used to estimate the effects of conditions on work
      impairments, controlling for sociodemographics. At least one illness-related work
      loss or work-cutback day in the past 30 days was reported by 22.4% of
      respondents, with a monthly average of 6.7 such days among those with any work
      impairment. This is equivalent to an annualized national estimate of over 2.5
      billion work-impairment days in the age range of the sample. Cancer is associated
      with by far the highest reported prevalence of any impairment (66.2%) and the
      highest conditional number of impairment days in the past 30 (16.4 days). Other
      conditions associated with high odds of any impairment include ulcers, major
      depression, and panic disorder, whereas other conditions associated with a large
      conditional number of impairment days include heart disease and high blood
      pressure. Comorbidities involving combinations of arthritis, ulcers, mental
      disorders, and substance dependence are associated with higher impairments than
      expected on the basis of an additive model. The effects of conditions do not
      differ systematically across subsamples defined on the basis of age, sex,
      education, or employment status. The enormous magnitude of the work impairment
      associated with chronic conditions and the economic advantages of interventions
      for ill workers that reduce work impairments should be factored into employer
      cost-benefit calculations of expanding health insurance coverage. Given the
      enormous work impairment associated with cancer and the fact that the vast
      majority of employed people who are diagnosed with cancer stay in the workforce
      through at least part of their course of treatment, interventions aimed at
      reducing the workplace costs of this illness should be a priority.

PMID- 11285870
TI  - p53 gene expression in relation to indoor exposure to unvented coal smoke in Xuan
      Wei, China.
AB  - Lung cancer mortality rates in Xuan Wei County, which are among the highest in
      China, have previously been associated with exposure to indoor emissions from
      burning smoky coal. To determine if this association is stronger among lung
      cancer patients with abnormal expression of p53, we performed a population-based
      case-control study. Ninety-seven newly diagnosed lung cancer patients and 97
      controls, individually matched by age, sex, and home fuel type, were enrolled. We
      used immunocytochemical methods to assess p53 protein accumulation in exfoliated
      tumor cells isolated from sputum samples. As expected, the amount of lifetime
      smoky coal use was associated with an overall increase in lung cancer risk.
      Compared with subjects who used less than 130 tons of smoky coal during their
      lifetime, the odds ratios (OR) for lung cancer were 1.48 (95% confidence interval
      [CI], 0.73 to 3.02) for subjects exposed to 130 to 240 tons, and 3.21 (95% CI,
      1.23 to 9.03) for subjects who used more than 240 tons of smoky coal (P for trend
      0.01). The effect was due almost exclusively to the pattern in women, almost all
      of whom were nonsmokers. Further, among highly exposed women, the association was
      substantially larger and achieved statistical significance only among patients
      with sputum samples that were positive for p53 overexpression (OR, 18.72; 95% CI,
      1.77 to 383.38 vs OR, 4.80; 95% CI, 0.66 to 43.87 for p53-negative cases). This
      study suggests that exposure to the combustion products of smoky coal in Xuan Wei
      is more strongly associated with women who have lung cancer accompanied by p53
      protein overexpression in exfoliated tumor cells.

PMID- 11285871
TI  - Efficacy of serial medical surveillance for chronic beryllium disease in a
      beryllium machining plant.
AB  - There is limited information on the use of the blood beryllium lymphocyte
      proliferation test (BeLPT) at regular intervals in medical surveillance.
      Employees of a beryllium machining plant were screened with the BeLPT biennially,
      and new employees were screened within 3 months of hire. Of 235 employees
      screened from 1995 to 1997, a total of 15 (6.4%) had confirmed abnormal BeLPT
      results indicating beryllium sensitization; nine of these employees were
      diagnosed with chronic beryllium disease. Four of the 15 cases were diagnosed
      within 3 months of first exposure. When 187 of the 235 employees participated in
      biennial screening in 1997 to 1999, seven more had developed beryllium
      sensitization or chronic beryllium disease, increasing the overall rate to 9.4%
      (22 of 235). The blood BeLPT should be used serially in beryllium disease
      surveillance to capture new or missed cases of sensitization and disease.
      Beryllium sensitization and chronic beryllium disease can occur within 50 days of
      first exposure in modern industry.

PMID- 11285872
TI  - Beryllium particulate exposure and disease relations in a beryllium machining
      plant.
AB  - We examined the relationship between exposure to beryllium and the presence of
      beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of
      workers in a beryllium precision machining facility. Twenty workers with BeS or
      CBD (cases) were compared with 206 worker-controls in a case-control study.
      Exposure for each job title was measured using cascade impactors placed in the
      workers' breathing zone to measure total beryllium exposure and exposure to
      particles < 6 microns and < 1 micron in aerodynamic diameter. Cumulative exposure
      was calculated as sigma (job title exposure estimate x years in job title).
      Individual lifetime-weighted (LTW) exposure was calculated as sigma [(job title
      exposure x years in job title) divided by total years employment)]. Workers in
      the case group were more likely to have worked as machinists (odds ratio, 4.4;
      95% confidence interval, 1.1 to 17.5) than those in the control group. The median
      cumulative exposure was consistently greater in the cases compared with the
      controls for all exposure estimates and particle size fractions, although this
      was not statistically significant. The median cumulative exposure was 2.9
      micrograms/m3-years in the cases versus 1.2 micrograms/m3-years in the controls
      for total exposure, and 1.7 micrograms/m3-years in the cases versus 0.5
      microgram/m3-years in the controls for exposure to particles < 6 microns in
      diameter. With cumulative exposure categorized into low-, intermediate-, and high
      exposure groups, the odds ratios were 2.4 (95% confidence interval, 0.7 to 8.2)
      for the intermediate-exposure group and 1.2 (95% confidence interval, 0.4 to 4.2)
      for the high-exposure group compared with the low-exposure group. The median LTW
      exposure was 0.25 microgram/m3 in both groups. The median LTW exposure to
      particles < 6 microns was 0.20 microgram/m3 in the cases compared with 0.14
      microgram/m3 in the controls. The differences in cumulative and LTW exposure were
      not statistically significant. None of the 22 workers with LTW exposure < 0.02
      microgram/m3 had BeS or CBD. Twelve workers (60%) in the case group had LTW
      exposures > 0.20. In conclusion, increased cumulative and LTW exposure to total
      and respirable beryllium was observed in workers with CBD or BeS compared with
      the controls. These results support efforts to control beryllium exposure in the
      workplace.

PMID- 11285873
TI  - Cancer mortality patterns among hairdressers and barbers in 24 US states, 1984 to
      1995.
AB  - We evaluated cancer mortality patterns among hairdressers and barbers, according
      to occupation, coded on 7.2 million death certificates in 24 states from 1984 to
      1995. Of the 38,721 deaths among white and black hairdressers and barbers of both
      sexes, 9495 were from all malignant neoplasms. Mortality odds ratios were
      significantly elevated for all malignant neoplasms, lung cancer, and all
      lymphatic and hemopoietic cancers among black and white female hairdressers.
      White female hairdressers had significant excess mortality from cancers of the
      stomach, colon, pancreas, breast, and bladder and from non-Hodgkin's lymphoma and
      lymphoid leukemia; mortality from these cancers was also elevated among black
      female hairdressers. White male hairdressers had significantly elevated mortality
      from non-melanoma skin cancer and non-Hodgkin's lymphoma. Mortality from all
      malignant neoplasms, although significantly elevated among both white and black
      female hairdressers, was significantly below the null for white male
      hairdressers. Black and white male barbers had significantly elevated mortality
      from stomach and pharyngeal cancer, respectively. A significant deficit in
      mortality from all neoplasms and cancers of the pancreas, lung, and prostate was
      noted for white male barbers. This large study of cancer mortality among
      hairdressers and barbers showed some differences in mortality patterns by gender
      and race. Further studies are required to determine if specific occupational
      exposures may explain some of the elevated cancer rates.

PMID- 11285874
TI  - Chemical sensitivity and chronic fatigue in Gulf War veterans: a brief report.
AB  - The foci of this brief report are to (1) describe the prevalence of chemical
      sensitivity (CS) and chronic fatigue (CF) symptomatology and of presumptive
      multiple CS and CF syndrome diagnoses, and (2) explore the potential overlap
      between one purported case definition (i.e., chronic multi-symptom illness) and
      these unexplained symptom syndromes in a well-characterized group of Gulf War
      veterans. The number of subjects with CS and CF symptomatology and presumptive
      multiple CS and CF syndrome diagnoses was higher in the Gulf War-deployed group
      compared with a group deployed to Germany during the Gulf War. However, the
      percent differences were not significant when comparing the presumptive diagnoses
      of multiple CS and CF syndrome. The characteristic differences between the groups
      and the overlap with chronic multi-symptom illness are also discussed.

PMID- 11285875
TI  - Health care utilization and workplace interventions for neck and upper limb
      problems among newspaper workers.
AB  - Data on the use of various therapeutic interventions among working populations at
      risk for musculoskeletal disorders are rare, despite the need for such
      information in assessing adherence to best practices. Using the results of a
      cross-sectional survey of newspaper workers who reported neck and upper limb pain
      or discomfort (n = 309), we describe the prevalence of a wide range of clinical
      and workplace interventions. Information/education, exercises, and physical
      treatments were the most common interventions, and work changes were less
      prevalent. Those with more frequent, longer-duration, and/or more severe symptoms
      more commonly reported visits to physiotherapists and health practitioners at
      work and use of physical treatments, medications, and devices. The multiplicity
      of interventions used pose evaluation challenges for occupational health
      practitioners and researchers.

PMID- 11285876
TI  - Modified work: prevalence and characteristics in a sample of workers with soft
      tissue injuries.
AB  - Modified-work programs are designed to facilitate the return to work for
      employees with a work-related injury. Although extensive published literature
      exists that describes and evaluates "ideal" programs, to date there is a paucity
      of data describing practice. To address this pertinent issue, we administered a
      survey to a large sample of 1833 workers with soft-tissue injuries in Ontario,
      Canada, and asked them detailed questions about modified work and employer
      contact. Our results reveal that most workers (66%) were contacted by someone
      from their workplace to check on how they were doing. However, only a minority
      (36%) were offered arrangements by their employer to help them return to work
      after developing a work-related soft-tissue injury. Most arrangements that were
      offered to injured workers consisted of such temporary modifications as reduced
      hours (24%), flexible work hours (25%), or a lighter job (57%) rather than more
      permanent changes to the way that work is conducted, such as changes to the work
      layout or equipment (8%). Merely being contacted by the workplace to check on how
      the worker was doing was not associated with reduced compensation benefit
      duration. Workplace offers of arrangements to help the worker return to work were
      associated with reduced compensation benefit duration but were not statistically
      associated with workers' pain grade.

PMID- 11285877
TI  - Time and knowledge barriers to recognizing occupational disease.
AB  - Traditionally, inadequate training has been considered the major barrier to
      recognition of occupational disease. A survey of 136 practitioners was conducted
      to determine which barriers were actually considered most relevant. The sample
      included three subgroups: primary care, occupational medicine-oriented, and
      Mexican. Four aggregate indices were derived: Knowledge, Time, Unpleasant
      aspects, and Importance. Inadequate Time was as important as inadequate
      Knowledge, whereas perceived lack of Importance and Unpleasant aspects were less
      relevant. Patterns among the subgroups were generally comparable. This study
      implies that training more occupational medicine specialists in increasing
      recognition is not sufficient unless specific strategies to overcome time
      constraints are also implemented. For example, emphasizing a "complete
      occupational history" may be counterproductive. Limiting histories to selected
      patients; use of focused, brief histories; and, perhaps, computer-based methods
      are needed.

PMID- 11285878
TI  - Long-term assessment of a sanitary education and lumbar rehabilitation program
      for health care workers with chronic low back pain at the University Hospital of
      Lille.
AB  - A back school was established in 1992 at the University Hospital of Lille
      (France) for employees with low back pain. We report its medical and
      socioeconomic benefits with a mean time to follow-up of 4 years. Our
      retrospective study included 108 health care workers and provides objective data
      (absenteeism, use of health care) and subjective information (progression of pain
      and disorder, social and professional impact) before training and a mean of 4
      years after training. We found that 92% of the participants were satisfied with
      the training and that back pain had regressed or resolved for 55% of them. Both
      the frequency and duration of pain had decreased significantly. Seventy percent
      continue to apply the advice they received in their everyday life. Dealing with
      the problems specific to professional activities contributed to reduce the strain
      experienced on the job by the health care workers and improved their satisfaction
      at work. Global absenteeism was reduced by 57.8%, whereas it was reduced by 33%
      for back pain alone 4 years after implementing this program. Our study provides
      evidence of the positive impact of this type of training on the way back pain is
      perceived and on everyday life. The assessment of the cost/efficiency ratio
      completes the list of durable benefits reported here.

PMID- 11285879
TI  - Chronic mercury exposure examined with a computer-based tremor system.
AB  - Tremor is being increasingly evaluated by quantitative computer-based systems to
      differentiate its causes. In this study, a group of mercury-exposed workers were
      assessed to determine whether tremor characteristics differed by exposure level.
      Workers were classified into two groups: those with an average urine mercury
      concentration below the American Conference of Government Industrial Hygienist
      Biological Exposure Index of 35 micrograms/g creatinine, and those with an
      average urine mercury concentration above the Biological Exposure Index. Tremor
      characteristics (including intensity, harmonic index, center frequency, standard
      deviation of the center frequency, and tremor index) were measured and recorded
      with a computer-based tremor system. Sixteen of 17 workers who were potentially
      exposed to mercury participated in the study. Three workers had a mean urine
      mercury concentration of 27.0 micrograms/g-creatinine and were assigned to the
      low-exposure group, and 13 workers had a mean urine mercury concentration of
      200.2 micrograms/g-creatinine and were assigned to the high-exposure group. There
      was a statistically significant difference in the tremor index (which compiles
      five individual tremor parameters into a single value) between the two groups (P
      = 0.04; Wilcoxon's rank sum test). Other tremor characteristics did not differ
      significantly between the groups. Tremor index may be more useful than measures
      of individual tremor parameters in differentiating normal from subclinical
      pathological tremors among groups of workers with chronic mercury exposure.

PMID- 11285880
TI  - Value of vertebral X-rays in osteoporosis.

PMID- 11285881
TI  - Bone density measurement techniques in the diagnosis and management of
      osteoporosis.

PMID- 11285882
TI  - Corticosteroid-induced osteoporosis.

PMID- 11285883
TI  - Therapy for osteoporosis.

PMID- 11285884
TI  - A wake-up call to South Carolina: and calling all doctors!

PMID- 11285885
TI  - Osteoporosis: a growing problem.

PMID- 11285886
TI  - Treatment and prevention of osteoporosis: future directions.
AB  - Osteoporosis is an important disease because of its prevalence and because it is
      associated with significant morbidity and mortality. As a consequence,
      development of new means of treating the disease is a major goal of drug
      companies. A number of new scientific discoveries have provided new rationales
      for development of new drugs that act either to inhibit bone resorption or to
      stimulate bone formation. These new drugs should greatly expand the therapeutic
      approach that can be used for treatment of this common disorder in the individual
      patient.

PMID- 11285887
TI  - Overview of hypoxia around the world.
AB  - No other environmental variable of such ecological importance to estuarine and
      coastal marine ecosystems around the world has changed so drastically, in such a
      short period of time, as dissolved oxygen. While hypoxic and anoxic environments
      have existed through geological time, their occurrence in shallow coastal and
      estuarine areas appears to be increasing, most likely accelerated by human
      activities. Several large systems, with historical data, that never reported
      hypoxia at the turn of the 19th century (e.g., Kattegat, the sea between Sweden
      and Denmark) now experience severe seasonal hypoxia. Synthesis of literature
      pertaining to benthic hypoxia and anoxia revealed that the oxygen budgets of many
      major coastal ecosystems have been adversely affected mainly through the process
      of eutrophication (the production of excess organic matter). It appears that many
      ecosystems that are now severely stressed by hypoxia may be near or at a
      threshold of change or collapse (loss of fisheries, loss of biodiversity,
      alteration of food webs).

PMID- 11285888
TI  - Seasonal hypoxia in the bottom water off the Mississippi River delta.
AB  - Hypoxia (oxygen concentration less than 2 mg L-1 or 62.5 mmol m-3) occurs on the
      Louisiana continental shelf during summer when the consumption of oxygen by
      sediment and water column respiration exceed resupply by photosynthesis and
      mixing. Biological processes that consume or produce oxygen have been summarized
      in a budget that can be used to quantify the degree to which consumption in deep
      water and in the sediments exceeds net production and thus the time it takes to
      reach hypoxic conditions following the spring onset of stratification. The net
      consumption rate by the sea floor biota (sediment oxygen consumption, SOC) is
      inversely related to oxygen concentration and directly related to temperature.
      Photosynthesis is of potential importance throughout the deep water column and on
      the sea floor when light is adequate. A non-steady state, time-dependent
      numerical simulation model is used to compare biological and physical processes
      with shipboard measurements and continuous near-bottom records. The simulations
      illustrate possible variations in oxygen concentration on time scales of hours to
      months, and these in general match much of the variability in the direct
      observations at time scales of days to weeks. The frequently observed unremitting
      anoxia lasting weeks at some locations is not produced in the present
      simulations. A possible explanation is the chemical oxidation in the water column
      of reduced metabolic end-products produced in the sediments by anaerobic
      metabolism. Direct measurements of biological processes could lead to better
      understanding of how extrinsic forcing functions can best be managed to improve
      water quality.

PMID- 11285889
TI  - Oxygen-deficient waters along the Japanese coast and their effects upon the
      estuarine ecosystem.
AB  - Development of hypoxia in Japan has been confirmed in the inner part of almost
      every major bay of Japan on the Pacific Coast from Tokyo southward. This paper
      presents multiple aspects (present condition, hydraulic mechanism, effect upon
      fisheries, historical progress and nutrient budget between sediment and water)
      using Mikawa Bay, where Japan's most serious hypoxia occurs, as an example.
      Although hypoxia basically results from the increase of nutrient load input from
      domestic and livestock sources, the intense reclamation of shallows (including
      tidal flats) and the large reduction in river flow due to farmland irrigation
      drastically accelerated dissolved oxygen deficiency. Oxygen-deficient waters in
      Mikawa Bay are large enough to strip the water purification capacity of the
      remaining shallows. Unfortunately, the shallows have turned from a purifier to a
      source of nutrient load. These conditions are more or less common in all bays
      where the dissolved oxygen-deficient waters have been reported. To break this
      cycle, dissolved oxygen deficiency must be contained to the extent that the
      purification capacity of the shallows can be restored to an efficient level. For
      this purpose, the first thing to do is to restore tidal flats over an extensive
      area and to recover sufficient water flow, which may be a more urgent imperative
      than reducing the nutrient load input.

PMID- 11285890
TI  - Chesapeake Bay eutrophication: scientific understanding, ecosystem restoration,
      and challenges for agriculture.
AB  - Chesapeake Bay has been the subject of intensive research on cultural
      eutrophication and extensive efforts to reduce nutrient inputs. In 1987 a
      commitment was made to reduce controllable sources of nitrogen (N) and
      phosphorous (P) by 40% by the year 2000, although the causes and effects of
      eutrophication were incompletely known. Subsequent research, modeling, and
      monitoring have shown that: (i) the estuarine ecosystem had been substantially
      altered by increased loadings of N and P of approximately 7- and 18-fold,
      respectively; (ii) hypoxia substantially increased since the 1950s; (iii)
      eutrophication was the major cause of reductions in submerged vegetation; and
      (iv) reducing nutrient sources by 40% would improve water quality, but less than
      originally thought. Strong public support and political commitment have allowed
      the Chesapeake Bay Program to reduce nutrient inputs, particularly from point
      sources, by 58% for P and 28% for N. However, reductions of nonpoint sources of P
      and N were projected by models to reach only 19% and 15%, respectively, of
      controllable loadings. The lack of reductions in nutrient concentrations in some
      streams and tidal waters and field research suggest that soil conservation-based
      management strategies are less effective than assumed. In 1997, isolated
      outbreaks of the toxic dinoflagellate Pfiesteria piscicida brought attention to
      the land application of poultry manure as a contributing factor to elevated soil
      P and ground water N concentrations. In addition to developing more effective
      agricultural practices, emerging issues include linking eutrophication and living
      resources, reducing atmospheric sources of N, enhancing nutrient sinks,
      controlling sprawling suburban development, and predicting and preventing harmful
      algal blooms.

PMID- 11285891
TI  - Hypoxia in the Gulf of Mexico.
AB  - Seasonally severe and persistent hypoxia, or low dissolved oxygen concentration,
      occurs on the inner- to mid-Louisiana continental shelf to the west of the
      Mississippi River and Atchafalaya River deltas. The estimated areal extent of
      bottom dissolved oxygen concentration less than 2 mg L-1 during mid-summer
      surveys of 1993-2000 reached as high as 16,000 to 20,000 km2. The distribution
      for a similar mapping grid for 1985 to 1992 averaged 8000 to 9000 km2. Hypoxia
      occurs below the pycnocline from as early as late February through early October,
      but is most widespread, persistent, and severe in June, July, and August. Spatial
      and temporal variability in the distribution of hypoxia exists and is, at least
      partially, related to the amplitude and phasing of the Mississippi and
      Atchafalaya discharges and their nutrient flux. Mississippi River nutrient
      concentrations and loadings to the adjacent continental shelf have changed
      dramatically this century, with an acceleration of these changes since the 1950s
      to 1960s. An analysis of diatoms, foraminiferans, and carbon accumulation in the
      sedimentary record provides evidence of increased eutrophication and hypoxia in
      the Mississippi River delta bight coincident with changes in nitrogen loading.

PMID- 11285892
TI  - Nitrogen input to the Gulf of Mexico.
AB  - Historical streamflow and concentration data were used in regression models to
      estimate the annual flux of nitrogen (N) to the Gulf of Mexico and to determine
      where the nitrogen originates within the Mississippi Basin. Results show that for
      1980-1996 the mean annual total N flux to the Gulf of Mexico was 1,568,000 t yr
      1. The flux was about 61% nitrate N, 37% organic N, and 2% ammonium N. The flux
      of nitrate N to the Gulf has approximately tripled in the last 30 years with most
      of the increase occurring between 1970 and 1983. The mean annual N flux has
      changed little since the early 1980s, but large year-to-year variations in N flux
      occur because of variations in precipitation. During wet years the N flux can
      increase by 50% or more due to flushing of nitrate N that has accumulated in the
      soils and unsaturated zones in the basin. The principal source areas of N are
      basins in southern Minnesota, Iowa, Illinois, Indiana, and Ohio that drain
      agricultural land. Basins in this region yield 1500 to more than 3100 kg N km-2
      yr-1 to streams, several times the N yield of basins outside this region.

PMID- 11285893
TI  - Nitrate nitrogen in surface waters as influenced by climatic conditions and
      agricultural practices.
AB  - Subsurface tile drainage from row-crop agricultural production systems has been
      identified as a major source of nitrate entering surface waters in the
      Mississippi River basin. Noncontrollable factors such as precipitation and
      mineralization of soil organic matter have a tremendous effect on drainage
      losses, nitrate concentrations, and nitrate loadings in subsurface drainage
      water. Cropping system and nutrient management inputs are controllable factors
      that have a varying influence on nitrate losses. Row crops leak substantially
      greater amounts of nitrate compared with perennial crops; however, satisfactory
      economic return with many perennials is an obstacle at present. Improving N
      management by applying the correct rate of N at the optimum time and giving
      proper credits to previous legume crops and animal manure applications will also
      lead to reduced nitrate losses. Nitrate losses have been shown to be minimally
      affected by tillage systems compared with N management practices. Scientists and
      policymakers must understand these factors as they develop educational materials
      and environmental guidelines for reducing nitrate losses to surface waters.

PMID- 11285894
TI  - Additives to reduce ammonia and odor emissions from livestock wastes: a review.
AB  - This paper reviews the use of additives to reduce odor and ammonia (NH3)
      emissions from livestock wastes. Reduction of NH3 volatilization has been shown
      to be possible, particularly with acidifying and adsorbent additives, and
      potential exists to develop further practical and cost-effective additives in
      this area. Masking, disinfecting, and oxidizing agents can provide short-term
      control of malodor, but as the capacity of these additives is finite, they
      require frequent reapplication. Microbial-based digestive additives may offer a
      solution to this problem as they are regenerative, but they appear to have been
      developed without a thorough understanding of microbiological processes occurring
      in livestock wastes. Currently, their use to reduce odor or NH3 emissions cannot
      be recommend. If the potential of these types of additives is to be realized,
      research needs to shift from simply evaluating these unknown products to
      investigating known strains of bacteria or enzymes with known modes of action. To
      protect the farmers' interest, standard independent test procedures are required
      to evaluate efficacy. Such tests should be simple and quantify the capacity of
      the additive to perform as claimed. The principle use of additives needs to be
      identified and addressed during their development. Producers may not use
      effective additives in one area if they further compound other problems that they
      perceived to be more important. There is the potential to use additives to treat
      other problems associated with livestock wastes, particularly to improve handling
      properties, reduce pollution potential to watercourses, and reduce pathogenic
      bacteria. Further work is required in these areas.

PMID- 11285895
TI  - Effect on water resources from upstream water diversion in the Ganges basin.
AB  - Bangladesh faces at least 30 upstream water diversion constructions of which
      Farakka Barrage is the major one. The effects of Farakka Barrage on water
      resources, socioeconomy, and culture have been investigated downstream in the
      basins of the Ganges and its distributaries. A diversion of up to 60% of the
      Ganges water over 25 yr has caused (i) reduction of water in surface water
      resources, (ii) increased dependence on ground water, (iii) destruction of the
      breeding and raising grounds for 109 species of Gangetic fishes and other aquatic
      species and amphibians, (iv) increased malnutrition, (v) deficiency in soil
      organic matter content, (vi) change in the agricultural practices, (vii)
      eradication of inland navigable routes, (viii) outbreak of waterborne diseases,
      (ix) loss of professions, and (x) obstruction to religious observances and
      pastimes. Further, arsenopyrites buried in the prebarrage water table have come
      in contact with air and formed water-soluble compounds of arsenic. Inadequate
      recharging of ground water hinders the natural cleansing of arsenic, and
      threatens about 75,000,000 lives who are likely to use water contaminated with up
      to 2 mg/L of arsenic. Furthermore, the depletion of surface water resources has
      caused environmental heating and cooling effects. Apart from these effects,
      sudden releases of water by the barrage during the flood season cause devestating
      floods. In consideration of such a heavy toll for the areas downstream, strict
      international rules have to be laid down to preserve the riparian ecosystems.

PMID- 11285896
TI  - Methane oxidation in two Swedish landfill covers measured with carbon-13 to
      carbon-12 isotope ratios.
AB  - The release of methane (CH4) from landfills to the atmosphere and the oxidation
      of CH4 in the cover soils were quantified with static chambers and a 13C-isotope
      technique on two landfills in Sweden. One of the landfills had been closed and
      covered 17 years before this investigation while the other was recently covered.
      On both landfills, the tops of the landfills were compared with the sloping parts
      in the summer and winter. Emitted CH4, captured in chambers, was significantly
      enriched in 13C during summer compared with winter (P < 0.0001), and was enriched
      relative to anaerobic-zone methane. The difference between emitted and anaerobic
      zone delta 13C-CH4 was used to estimate soil methane oxidation. In summer, these
      differences ranged from 9 to 26@1000, and CH4 oxidation was estimated to be
      between 41 and 50% of the produced CH4 in the new landfill, and between 60 and
      94% in the old landfill. In winter, when soil temperature was below 0 degree C,
      no difference in delta 13C was observed between emitted and anaerobic-zone CH4,
      suggesting that there was no soil oxidation. The temperature effect shown in this
      experiment suggests that there may be both seasonal and latitudinal differences
      in the importance of landfill CH4 oxidation. Finally the isotopic fractionation
      factor (alpha) varied from 1.023 to 1.038 and was temperature dependent,
      increasing at colder temperatures. Methanotrophic bacteria appeared to have high
      growth efficiencies and the majority of the methane consumed in incubations did
      not result in immediate CO2 production.

PMID- 11285897
TI  - Greenhouse gas emissions during cattle feedlot manure composting.
AB  - The emission of greenhouse gases (GHG) during feedlot manure composting reduces
      the agronomic value of the final compost and increases the greenhouse effect. A
      study was conducted to determine whether GHG emissions are affected by composting
      method. Feedlot cattle manure was composted with two aeration methods--passive
      (no turning) and active (turned six times). Carbon lost in the forms of CO2 and
      CH4 was 73.8 and 6.3 kg C Mg-1 manure for the passive aeration treatment and
      168.0 and 8.1 kg C Mg-1 manure for the active treatment. The N loss in the form
      of N2O was 0.11 and 0.19 kg N Mg-1 manure for the passive and active treatments.
      Fuel consumption to turn and maintain the windrow added a further 4.4 kg C Mg-1
      manure for the active aeration treatment. Since CH4 and N2O are 21 and 310 times
      more harmful than CO2 in their global warming effect, the total GHG emission
      expressed as CO2-C equivalent was 240.2 and 401.4 kg C Mg-1 manure for passive
      and active aeration. The lower emission associated with the passive treatment was
      mainly due to the incomplete decomposition of manure and a lower gas diffusion
      rate. In addition, turning affected N transformation and transport in the window
      profile, which contributed to higher N2O emissions for the active aeration
      treatment. Gas diffusion is an important factor controlling GHG emissions. Higher
      GHG concentrations in compost windrows do not necessarily mean higher production
      or emission rates.

PMID- 11285898
TI  - Greenhouse gases in non-oxygenated and artificially oxygenated eutrophied lakes
      during winter stratification.
AB  - Concentrations of dissolved methane (CH4), carbon dioxide (CO2), and nitrous
      oxide (N2O) were measured in the water columns of non-oxygenated and artificially
      oxygenated, ice-covered eutrophied lakes in the mid-boreal zone in Finland during
      late winter 1997 and 1999. Sampling was conducted during winter stratification,
      the critical period for oxygen (O2) deficiency in seasonally ice-covered,
      thermally stratified lakes. Oxygen concentrations were maintained at least at a
      moderate level throughout the oxygenated water columns, whereas the non
      oxygenated columns suffered anoxic hypolimnia. The mean concentrations of
      dissolved CH4 exceeding the atmospheric equilibrium were greater in the non
      oxygenated water columns (20.6-154 microM) than in the oxygenated ones (0.01-1.41
      microM). In contrast, the mean excess CO2 concentrations varied less between the
      non-oxygenated and oxygenated sites (0.28-0.47 and 0.25-0.31 mM, respectively).
      Oxygenated water columns had greater mean excess concentrations of N2O (0.018
      0.032 microM) than the non-oxygenated ones (0.005-0.024 microM). If the
      accumulated greenhouse gas stores in the water columns during winter are assumed
      to be released to the atmosphere during the spring overturn, the global warming
      potentials (GWP, time horizon 100 yr) of these potential emissions at the non
      oxygenated, eutrophic study sites ranged from 177 to 654 g CO2 equivalent (CO2-e)
      m-2 compared with 144 to 173 g CO2-e m-2 at the oxygenated sites. The increase in
      the accumulation of CH4 was the main reason for the higher GWP of the non
      oxygenated sites. Anthropogenic eutrophication of lake ecosystems can generate
      increased CH4 emissions due to associated O2 depletion of their sediment and
      water column.

PMID- 11285899
TI  - Phytoremediation of aged petroleum sludge: effect of inorganic fertilizer.
AB  - Phytoremediation is a promising new technology that uses higher plants to enhance
      biodegradation. Nutrient availability is an important factor governing the
      success of phytoremediation and can be regulated through the addition of
      fertilizer. A greenhouse study was conducted to assess the importance of nitrogen
      and phosphorus for the phytoremediation of petroleum sludge. Degradation of total
      petroleum hydrocarbons (TPH) was quantified for six fertilization rates and three
      vegetation treatments: bermuda grass [Cynodon dactylon (L.) Pers.], tall fescue
      (Festuca arundinacea Schreb.), and an unvegetated control. During the first 6 mo
      of the experiment, TPH declined by an average of 49% with no significant
      differences between treatments. After 1 yr, TPH degradation was significantly
      greater in both vegetated treatments with a mean TPH reduction of 68% for
      bermuda, 62% for fescue, and 57% for the unvegetated control. Degradation of TPH
      in the fescue and bermuda treatments was significantly lower in the treatments in
      which no fertilizer was added or N and P were added simply to maintain plant
      growth compared with the higher rates of fertilization. For this short-term,
      greenhouse experiment, optimal remediation was obtained by fertilization that
      produced a C to N to P ratio of 100:2:0.2.

PMID- 11285900
TI  - Solid-state nitrogen-15 nuclear magnetic resonance analysis of biologically
      reduced 2,4,6-trinitrotoluene in a soil slurry remediation.
AB  - Soil contaminated with 2,4,6-trinitrotoluene (TNT) and spiked with [14C]- and
      [15N3]-TNT was subjected to an anaerobic-aerobic soil slurry treatment and
      subsequently analyzed by radiocounting and solid-state 15N nuclear magnetic
      resonance (NMR) spectroscopy. This treatment led to a complete disappearance of
      extractable radioactivity originating from TNT and almost all of the
      radioactivity was recovered in the insoluble soil fraction. As revealed by solid
      state 15N NMR, a major fraction of partially reduced metabolites of TNT was
      immobilized into the soil during the early stage of the anaerobic treatment,
      although some of the compounds (i.e., aminodinitrotoluenes and azoxy compounds)
      were extractable by methanol. Considerable 15N intensity was assigned to
      condensation products of TNT metabolites. A smaller signal indicated the
      formation of azoxy N. This signal and the signal for nitro groups were not
      observed at the end of the anaerobic phase, revealing further reduction and/or
      transformation of their corresponding compounds. An increase of the relative
      proportion of the condensation products occurred with increasing anaerobic
      incubation. Aerobic incubation resulted in a further decrease of aromatic amines,
      presumably due to oxidative transformations or their involvement in further
      condensation reactions. The results of the study demonstrate that the anaerobic
      aerobic soil slurry treatment represents an efficient strategy for immobilizing
      reduced TNT in soils.

PMID- 11285901
TI  - Metalaxyl toxicity, uptake, and distribution in several ornamental plant species.
AB  - Phytoremediation depends on the ability of plants to tolerate and assimilate
      contaminants. This research characterized the interaction between several
      ornamental plant species and the fungicidal active ingredient, metalaxyl [N-(2,6
      dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester]. Species evaluated
      included sweetflag (Acorus gramineus Sol. ex Aiton), canna (Canna hybrida L.
      'Yellow King Humbert'), parrotfeather [Myriophyllum aquaticum (Vell.) Verdc.],
      and pickerelweed (Pontederia cordata L.). Metalaxyl tolerance levels for each
      species were determined by exposing plants for 7 d to solutions containing 0, 5,
      10, 25, 50, 75, or 100 mg metalaxyl L-1 aqueous nutrient media. Response
      endpoints included fresh mass production after 7 d exposure and 7 d post-exposure
      and quantum efficiency using dark-adapted (Fv/Fm) and light-adapted (fluorescence
      yields) plants. Metalaxyl uptake and distribution within the plant was determined
      by growing plants in aqueous nutrient media containing 1.18 x 10(6) Bq L-1
      [14C]metalaxyl (0.909 mg L-1) for 1, 3, 5, or 7 d. Plant tissues were combusted
      and analyzed by liquid scintillation counting. Metalaxyl had no effects on the
      endpoints measured, except for fresh mass production of sweetflag at the 75 and
      100 mg L-1 treatment levels. However, leaf necrosis was apparent in most species
      after 5 d exposure to concentrations greater than 25 mg L-1. Metalaxyl removal
      from the spiked nutrient media ranged from 15 to 60% during the 7-d exposure
      period. The majority of metalaxyl removed from the solution was detected within
      individual plants. In nearly all cases, activity from the radiolabeled pesticide
      accumulated in the leaves. Uptake of metalaxyl was correlated with water uptake
      throughout the 7 d. These results suggest that all species examined may be good
      candidates for incorporation into a phytoremediation scheme for metalaxyl.

PMID- 11285902
TI  - Removal of herbicides from liquid media by fungi isolated from a contaminated
      soil.
AB  - Fungi were isolated from soil samples corresponding to pesticide-contaminated
      soil (CS) and noncontaminated soil (NCS) in the Annaba vicinity (Algeria) and
      identified. The number of isolates obtained from CS and NCS were 263 and 288,
      respectively. The most frequent species (Aspergillus fumigatus, A. niger, A.
      terreus, Absidia corymbifera, and Rhizopus microsporus var microsporus) were not
      sensitive to the pesticides. The growth of the genus Trichoderma was inhibited by
      the pesticides, while genera Absidia and Fusarium were stimulated. The 53 species
      isolated were assayed for their ability to remove metribuzin from liquid medium.
      Only Botrytis cinerea from NCS and Sordaria superba and Absidia fusca from CS
      removed more than 50% of the compound after 5 d. Metamitron was very resistant.
      Among the 21 species tested, only Alternaria solani (from NCS), Drechslera
      australiensis (from CS and NCS), and Absidia fusca (from CS) reduced the
      concentration in the medium more than 10% (10-16%). Twelve species were grown
      with linuron, seven of them were inefficient in removing this compound. The two
      strains of Sordaria macrospora yielded 22 to 25% depletion, while Botrytis
      cinerea depleted linuron almost completely. Among the 31 species assayed for
      their ability to eliminate metobromuron, Botrytis cinerea (from CS and NCS)
      depleted almost completely the chemical from the medium. Rhizopus oryzae and
      Absidia fusca from CS removed 40 and 47% of the compound, respectively. No
      systematic relationships were observed between the soil contamination and
      herbicide elimination capacities of soil fungi. Absidia fusca and Botrytis
      cinerea were particularly interesting for bioremediation purposes because they
      were able to transform efficiently three of the four compounds assayed.

PMID- 11285903
TI  - Hardwood seeding root and nutrient parameters for a model of nutrient uptake.
AB  - Use of mechanistic models is an increasingly accepted way to evaluate complex
      processes. The Barber-Cushman model provides a means to simulate nutrient uptake
      once information on root system characteristics, nutrient uptake, and soil
      nutrient supply are developed. Objectives of this study were to determine during
      a growing season: (i) root growth for 1-yr-old black cherry (Prunus serotina
      Ehrh.), northern red oak (Quercus rubra L.), and red maple (Acer rubrum L.)
      seedlings; (ii) net plant increase in N, P, K, Ca, and Mg; (iii) soil solution
      and solid phase nutrient concentrations; and (iv) the influence of root growth
      and soil nutrient supply changes on nutrient uptake using the Barber-Cushman
      model. Seedlings were grown in pots containing A horizon soil from two forest
      sites. Measurements were made on five occasions during the growing season. Root
      growth averaged 41.5 cm d-1 for red maple compared with 28.0 and 16.7 cm d-1 for
      cherry and oak, respectively. Seventy-five percent of root growth occurred at the
      end of the growing season. Total plant N showed the greatest change (25-58%) due
      to soil source. Model simulations underestimated observed uptake by 31 to 99%. A
      clear relationship between soil solution nutrient concentration and plant uptake,
      an important assumption of the model, was not observed. Results indicate care
      will need to be exercised in the development and use of root growth and nutrient
      supply values in mechanistic models.

PMID- 11285904
TI  - Bermudagrass fertilized with slow-release nitrogen sources. I. Nitrogen uptake
      and potential leaching losses.
AB  - With the objectives of analyzing N recovery and potential N losses in the warm
      season hybrid bermudagrass 'Tifgreen' [Cynodon dactylon (L.) Pers. x C.
      transvaalensis Burtt-Davy], two greenhouse studies were conducted. Plugs were
      planted in PVC cylinders filled with a modified sandy growing medium. Urea (URE),
      sulfur-coated urea (SCU), and Hydroform (HYD) (Hydro Agri San Francisco, Redwood
      City, CA) were broadcast at rates of 100 and 200 kg N ha-1 every 20 and 40 d. The
      grass was clipped three times every 10 d and analyzed for N concentration and N
      yield. In addition, leachates were analyzed for NO3-N. Use of the least soluble
      source, HYD, resulted in the lowest average clipping N concentration and N yield,
      as compared with SCU and URE. Clipping N concentration and N yield showed a
      cyclic pattern through time, particularly under long-day (> 12 h) conditions.
      When the photoperiod decreased below 12 h, leachate NO3-N concentration exceeded
      the standard limit for drinking water (10 mg L-1) by 10 to 19 times with the high
      SCU and URE application rate and frequency. However, leaching N losses
      represented a minimal fraction (< 1%) of the total applied N. More applied N was
      recovered in plant tissues using SCU and URE (89.5%) than using HYD (64.1%), with
      more than 52% of applied N accumulating in clipping. Highly insoluble N sources
      such as HYD decrease N leaching losses but may limit bermudagrass growth and
      quality. Risks of NO3-N losses in bermudagrass can be avoided by proper
      fertilization and irrigation programs, even when a highly soluble N source is
      used.

PMID- 11285905
TI  - Summary of well water sampling in California to detect pesticide residues
      resulting from nonpoint-source applications.
AB  - This report summarizes well sampling protocols, data collection procedures, and
      analytical results for the presence of pesticides in ground water developed by
      the California Department of Pesticide Regulation (DPR). Specific well sampling
      protocols were developed to meet regulatory mandates of the Pesticide
      Contamination Prevention Act (PCPA) of 1986 and to provide further understanding
      of the agronomic, chemical, and geographic factors that contribute to movement of
      residues to ground water. The well sampling data have formed the basis for the
      DPR's regulatory decisions. For example, a sampling protocol, the Four-Section
      Survey, was developed to determine if reported detections were caused by nonpoint
      source agricultural applications, a determination that can initiate formal review
      and subsequent regulation of a pesticide. Selection of sampling sites, which are
      primarily rural domestic wells, was initially based on pesticide use and cropping
      patterns. Recently, soil and depth-to-ground water data have been added to
      identify areas where a higher frequency of detection is expected. In accordance
      with the PCPA, the DPR maintains a database for all pesticide well sampling in
      California with submission required by all state agencies and with invitations
      for submission extended to all local and federal agencies or other entities. To
      date, residues for 16 active ingredients and breakdown products have been
      detected in California ground water as a result of legal agricultural use.
      Regulations have been adopted for all detected parent active ingredients, and
      they have been developed regardless of the level of detection.

PMID- 11285906
TI  - Immobilization of nickel and other metals in contaminated sediments by
      hydroxyapatite addition.
AB  - Batch experiments were conducted to evaluate the ability of hydroxyapatte (HA) to
      reduce the solubility of metals, including the primary contaminants of concern,
      Ni and U, from contaminated sediments located on the Department of Energy's
      Savannah River Site, near Aiken, SC. Hydroxyapatitie was added to the sediments
      at application rates of 0, 5, 15.8, and 50 g kg-1. After equilibrating in either
      0.02 M KCl or 0.01 M CaCl2, the samples were centrifuged and the supernatants
      filtered prior to metal, dissolved organic C, and PO4 analyses. The treated soils
      were then air-dried and changes in solid-phase metal distribution were evaluated
      using sequential extractions and electron-based microanalysis techniques.
      Hydroxyapatite was effective at reducing the solubility of U and, to a lesser
      degree, Ni. Hydroxyapatite was also effective in reducing the solubility of Al,
      Ba, Cd, Co, Mn, and Pb. Sequential extractions indicate that HA transfers such
      metals from more chemically labile forms, such as the water-soluble and
      exchangeable fractions, by altering solid-phase speciation in favor of secondary
      phosphate precipitates. Hydroxyapatite effectiveness was somewhat reduced in the
      presence of soluble organics that likely increased contaminant metal solubility
      through complexation. Arsenic and Cr solubility increased with HA addition,
      suggesting that the increase in pH and competition from PO4 reduced sorption of
      oxyanion contaminants. Energy dispersive x-ray (EDXA) analysis conducted in the
      transmission electron microscope (TEM) confirmed that HA amendment sequesters U,
      Ni, Pb, and possibly other contaminant metals in association with secondary Al
      phosphates.

PMID- 11285907
TI  - Removal of uranium(VI) from contaminated sediments by surfactants.
AB  - Uranium(VI) sorption onto a soil collected at the Melton Branch Watershed (Oak
      Ridge National Laboratory, TN) is strongly influenced by the pH of the soil
      solution and, to a lesser extent, by the presence of calcium, suggesting specific
      chemical interactions between U(VI) and the soil matrix. Batch experiments
      designed to evaluate factors controlling desorption indicate that two anionic
      surfactants, AOK and T77, at concentrations ranging from 60 to 200 mM, are most
      suitable for U(VI) removal from acidic soils such as the Oak Ridge sediment.
      These surfactants are very efficient solubilizing agents at low uranium
      concentrations: ca. 100% U(VI) removal for [U(VI)]o,sorbed = 10(-6) mol kg-1. At
      greater uranium concentrations (e.g., [U(VI)]o,sorbed = ca. 10(-5) mol kg-1), the
      desorption efficiency of the surfactant solutions increases with an increase in
      surfactant concentration and reaches a plateau of 75 to 80% of the U(VI)
      initially sorbed. The most probable mechanisms responsible for U(VI) desorption
      include cation exchange in the electric double layer surrounding the micelles
      and, to a lesser extent, dissolution of the soil matrix. Limitations associated
      with the surfactant treatment include loss of surfactants onto the soil
      (sorption) and greater affinity between U(VI) and the soil matrix at large soil
      to liquid ratios. Parallel experiments with H2SO4 and carbonate-bicarbonate (CB)
      solutions indicate that these more conventional methods suffer from strong matrix
      dissolution with the acid and reduced desorption efficiency with CB due to the
      buffering capacity of the acidic soil.

PMID- 11285908
TI  - Stability constants for the complexation of various metals with a rhamnolipid
      biosurfactant.
AB  - The presence of toxic metals in natural environments presents a potential health
      hazard for humans. Metal contaminants in these environments are usually tightly
      bound to colloidal particles and organic matter. This represents a major
      constraint to their removal using currently available in situ remediation
      technologies. One technique that has shown potential for facilitated metal
      removal from soil is treatment with an anionic microbial surfactant, rhamnolipid.
      Successful application of rhamnolipid in metal removal requires knowledge of the
      rhamnolipid-metal complexation reaction. Therefore, our objective was to evaluate
      the biosurfactant complexation affinity for the most common natural soil and
      water cations and for various metal contaminants. The conditional stability
      constant (log K) for each of these metals was determined using an ion-exchange
      resin technique. Results show the measured stability constants follow the order
      (from strongest to weakest): Al3+ > Cu2+ > Pb2+ > Cd2+ > Zn2+ > Fe3+ > Hg2+ >
      Ca2+ > Co2+ > Ni2+ > Mn2+ > Mg2+ > K+. These data indicate that rhamnolipid will
      preferentially complex metal contaminants such as lead, cadmium, and mercury in
      the presence of common soil or water cations. The measured rhamnolipid-metal
      stability constants were found in most cases to be similar or higher than
      conditional stability constants reported in the literature for metal complexation
      with acetic acid, oxalic acid, citric acid, and fulvic acids. These results help
      delineate the conditions under which rhamnolipid may be successfully applied as a
      remediation agent in the removal of metal contaminants from soil, as well as
      surface waters, ground water, and wastestreams.

PMID- 11285909
TI  - Fractionation and mobility of copper, lead, and zinc in soil profiles in the
      vicinity of a copper smelter.
AB  - Four soil profiles located near a copper smelter in Poland were investigated for
      the distribution and chemical fractions of Cu, Pb, and Zn and their mobility in
      relation to soil properties. Contamination with heavy metals was primarily
      restricted to surface horizons and the extent of contamination was 7- to 115-fold
      for Cu, 30-fold for Pb, and 6-fold for Zn as compared with subsurface horizons.
      In the less-contaminated fine-textured soil, the metals were distributed in the
      order: residual >> Fe-Mn oxides occluded > organically complexed > exchangeable
      and specifically adsorbed, while the order for sandy soils was: residual >
      organically complexed > Fe-Mn oxides occluded > exchangeable and specifically
      adsorbed. The contaminated surface horizons of these profiles showed no
      consistent pattern of metal distribution. However, the common features of highly
      contaminated soils were very low percentage of residual fraction and the
      dominance of the NH4OAc extractable fraction. The sum of mobile metal fractions
      was generally < 10% in subsurface horizons, while in the contaminated surface
      horizons these fractions made up 50% of the total metal contents. Soil properties
      contributed more to the relative distribution of the metal fractions in the
      studied profiles than did the distance and direction to the source of pollution.
      The amounts of metal extracted by 0.01 M CaCl2 accounted for only a small part of
      the same metals extracted by NH4OAc. The mobility indexes of metals correlated
      positively and significantly with the total content of metals and negatively with
      the clay content.

PMID- 11285910
TI  - Use of diammonium phosphate to reduce heavy metal solubility and transport in
      smelter-contaminated soil.
AB  - Phosphate treatments can reduce metal dissolution and transport from contaminated
      soils. However, diammonium phosphate (DAP) has not been extensively tested as a
      chemical immobilization treatment. This study was conducted to evaluate DAP as a
      chemical immobilization treatment and to investigate potential solids controlling
      metal solubility in DAP-amended soils. Soil contaminated with Cd, Pb, Zn, and As
      was collected from a former smelter site. The DAP treatments of 460, 920, and
      2300 mg P kg-1 and an untreated check were evaluated using solute transport
      experiments. Increasing DAP decreased total metal transported. Application of
      2300 mg P kg-1 was the most effective for immobilizing Cd, Pb, and Zn eluted from
      the contaminated soil. Metal elution curves fitted with a transport model showed
      that DAP treatment increased retardation (R) 2-fold for Cd, 6-fold for Zn, and
      3.5-fold for Pb. Distribution coefficients (Kd) increased with P application from
      4.0 to 9.0 L kg-1 for Cd, from 2.9 to 10.8 L kg-1 for Pb, and from 2.5 to 17.1 L
      kg-1 for Zn. Increased Kd values with additional DAP treatment indicated reduced
      partitioning of sorbed and/or precipitated metal released to mobile metal phases
      and a concomitant decrease in the concentration of mobile heavy metal species.
      Activity-ratio diagrams indicated that DAP decreased solution Cd, Pb, and Zn by
      forming metal-phosphate precipitates with low solubility products. These results
      suggest that DAP may have potential for protecting water resources from heavy
      metal contamination near smelting and mining sites.

PMID- 11285911
TI  - Effects of elevated carbon dioxide on soils in a Florida scrub oak ecosystem.
AB  - The results of a 3-yr study on the effects of elevated CO2 on soil N and P, soil
      pCO2, and calculated CO2 efflux in a fire-regenerated Florida scrub oak ecosystem
      are summarized. We hypothesized that elevated CO2 would cause (i) increases in
      soil pCO2 and soil respiration and (ii) reduced levels of soil-available N and P.
      The effects of elevated CO2 on soil N availability differed according to the
      method used. Results of resin lysimeter collections and anion exchange membrane
      tests in the field showed reduced NO3- in soils in Years 1 and 3. On the other
      hand, re-analysis of homogenized, buried soil bags after 1 yr suggested a
      relative increase in N availability (lower C to N ratio) under elevated CO2. In
      the case of P, the buried bags and membranes suggested a negative effect of CO2
      on P during the first year; this faded over time, however, as P availability
      declined overall, probably in response to P uptake. Elevated CO2 had no effect on
      soil pCO2 or calculated soil respiration at any time, further suggesting that
      plant rather than microbial uptake was the primary factor responsible for the
      observed changes in N and P availability with elevated CO2.

PMID- 11285912
TI  - Approximating phosphorus release from soils to surface runoff and subsurface
      drainage.
AB  - Phosphorus application in excess of crop needs has increased the concentration of
      P in surface soil and runoff and led many states to develop P-based nutrient
      management strategies. However, insufficient data are available relating P in
      surface soil, surface runoff, and subsurface drainage to develop sound
      guidelines. Thus, we investigated P release from the surface (0-5 cm depth) of a
      Denbigh silt loam from Devon, U.K. (30-160 mg kg-1 Olsen P) and Alvin, Berks,
      Calvin, and Watson soils from Pennsylvania (10-763 mg kg-1 Mehlich-3 P) in
      relation to the concentration of P in surface runoff and subsurface drainage. A
      change point, where the slopes of two linear relationships between water- or
      CaCl2-extractable soil P and soil test phosphorus (STP) (Olsen or Mehlich-3)
      meet, was evident for the Denbigh at 33 to 36 mg kg-1 Olsen P, and the Alvin and
      Berks soils at 185 to 190 mg Mehlich-3 P kg-1. Similar change points were also
      observed when STP was related to the P concentration of surface runoff (185 mg kg
      1) and subsurface drainage (193 mg kg-1). The use of water and CaCl2 extraction
      of surface soil is suggested to estimate surface runoff P (r2 of 0.92 for UK and
      0.86 for PA soils) and subsurface drainage P (r2 of 0.82 for UK and 0.88 for PA
      soils), and to determine a change point in STP, which may be used in support of
      agricultural and environmental P management.

PMID- 11285913
TI  - On the interaction mechanisms of atrazine and hydroxyatrazine with humic
      substances.
AB  - Atrazine (6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine) is retained
      against leaching losses in soils principally by sorption to organic matter, but
      the mechanism of sorption has been a matter of controversy. Conflicting evidence
      exists for proton transfer, electron transfer, and hydrophobic interactions
      between atrazine and soil humus, but no data are conclusive. In this paper we add
      to the database by investigating the role of (i) hydroxyatrazine (6-hydroxy-N2
      ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine) and (ii) hydrophobicity in the
      sorption of atrazine by Brazilian soil humic substances. We demonstrate,
      apparently for the first time, that hydroxyatrazine readily forms electron
      transfer complexes with humic substances. These complexes probably are the cause
      of the well-known strong adsorption by humic acids and they may be the undetected
      cause of apparent electron-transfer complexes between soil organic matter and
      atrazine, whose transformation to the hydroxy form is facile. We also present
      evidence that supports the important contribution of hydrophobic interactions to
      the pH-dependent sorption of atrazine by humic substances.

PMID- 11285914
TI  - Sorption of polycyclic aromatic compounds to humic and fulvic acid HPLC column
      materials.
AB  - Two different humic acids (HA) and a fulvic acid (FA) were chemically immobilized
      to a high performance liquid chromatography (HPLC) silica column material. The
      immobilization was performed by binding amino groups in HA/FA to the free
      aldehyde group in glutardialdehyde attached to the silica gel. The HPLC column
      materials were compared with a blank column material made by applying the same
      procedure but without immobilizing HA or FA. Also, a column was made by binding
      carbonyl groups in HA to amino groups attached to the silica gel. The humic
      substances were selected to secure appropriate variation of their structural
      features. The retention factors of 45 polycyclic aromatic compounds (PAC) to the
      four columns were determined by HPLC. The advantage of the technique is a large
      number of compounds can easily be studied. The binding procedure does not appear
      to cause a drastic selection between the HA molecules. The k' values obtained for
      the two Aldrich HA columns agree in general reasonably. The retention or sorption
      of the compounds increased with the size of the PAC and the number of lipophilic
      substituents, but decreased when polar substituents were present. The PAC
      retention was much stronger to the two HA columns than to the FA and blank
      column, both for hydrophobic polycyclic aromatic hydrocarbons (PAH) and the polar
      PAC. Other factors impacting the PAC binding may be specific interactions with HA
      and the ionic strength of the aqueous phase. The technique has been applied to do
      direct determinations of Koc.

PMID- 11285915
TI  - The selective removal of phosphorus from soil: is event size important?
AB  - Data from the Woburn Erosion Reference Experiment (Bedfordshire, UK) were used to
      test the hypothesis that losses of phosphorus (P) in small erosion events are as
      great as those in infrequent large events, and to examine the effect of storm
      characteristics on the selective enrichment of P in eroded sediment. For almost
      every plot event in the period 1988 to 1994, the clay-sized fraction of the
      sediment was enriched compared with the soil of the plots. There was more
      variation in clay enrichment for smaller erosion events than for larger ones. The
      clay and P contents of the sediment were strongly correlated (p < 0.01), and
      there was a wider range of P concentrations in the sediment derived from small
      events than in that from large events. However, individual events resulting in
      small soil losses (< 100 kg) did not account for greater P losses than larger
      events (> 100 kg). The greater frequency of smaller events, combined with the
      likelihood of higher P concentrations in the sediment, therefore accounted for a
      greater proportion of the P lost over the 6-yr period than the infrequent large
      events. Phosphorus concentrations generally increased with increasing peak
      discharge and decreased with increasing event duration. For the same return
      period, P losses were generally greater from plots cultivated up and down the
      slope than from those cultivated across the slope. Overall, our results suggest
      that small erosion events should be controlled to prevent P contamination of
      surface waters and that the most effective means of doing this are by the
      introduction of minimal tillage techniques and across-slope cultivations.

PMID- 11285916
TI  - Phosphorus mobilization from various sediment pools in response to increased pH
      and silicate concentration.
AB  - Phosphorus (P) release from sediment particles to the interstitial water has been
      studied extensively, but the contribution of different inorganic P pools in
      sediment under differing environmental conditions is not fully understood. This
      study was undertaken to get more detailed information about the chemical
      mobilization mechanisms. Phosphorus mobilization from reserves bound by Al, Fe,
      and Ca compounds in response to increased pH and to inorganic silicon (Si)
      enrichments was investigated using a sequential fractionation analysis and an
      isotope-labeling technique. The aerobic sediment of Lake Vesijarvi had a high P
      retention capacity, and Fe-bound P was the largest inorganic P pool as well as
      the main source of released P. High Si addition (47 mg Si L-1 sediment) released
      more P to the interstitial water than did the elevation of pH from 6.6 to 9.5,
      since Si lowered the resorption of released P onto hydrated Al oxides. This
      finding reveals that P equilibrium between Fe-bound and Al-bound P in sediments
      regulates P net mobilization to the interstitial water under aerobic conditions.
      Furthermore, elevated pH combined with high Si enrichment had a positive
      synergistic effect, resulting in the most substantial P mobilization. This
      synergism may cause a self-fueled increase in the internal loading of P. It
      accentuates the effect of diatom sedimentation on P fluxes in eutrophic lakes
      with high pH and may favor the appearance of bloom-forming cyanobacteria.

PMID- 11285917
TI  - Measurement and modeling of diclosulam runoff under the influence of simulated
      severe rainfall.
AB  - A runoff study was conducted near Tifton, GA to measure the losses of water,
      sediment, and diclosulam (N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro
      [1,2,4]triazolo-[1,5c]-pyrimidine- 2-sulfonamide), a new broadleaf herbicide,
      under a 50-mm-in-3-h simulated rainfall event on three separate 0.05-ha plots.
      Results of a runoff study were used to validate the Pesticide Root Zone Model
      (PRZM, v. 3.12) using field-measured soil, chemical, and weather inputs. The
      model-predicted edge-of-field diclosulam loading was within 1% of the average
      observed diclosulam runoff from the field study; however, partitioning between
      phases was not as well predicted. The model was subsequently used with worst-case
      agricultural practice inputs and a 41-yr weather record from Dublin, GA to
      simulate edge-of-field runoff losses for the two most prevalent soils (Tifton and
      Bibb) in the southeastern U.S. peanut (Arachis hypogaea L.) market for 328
      simulation years, and showed that the 90th percentile runoff amounts, expressed
      as percent of applied diclosulam, were 1.8, 0.6, and 5.2% for the runoff study
      plots and Tifton and Bibb soils, respectively. The runoff study and modeling
      indicated that more than 97% of the total diclosulam runoff was transported off
      the field by water, with < 3% associated with the sediment. Diclosulam losses due
      to runoff can be further reduced by lower application rates, tillage and crop
      residue management practices that reduce edge-of-field runoff, and conservation
      practices such as vegetated filter strips.

PMID- 11285918
TI  - Tillage, intercrop, and controlled drainage-subirrigation influence atrazine,
      metribuzin, and metolachlor loss.
AB  - Atrazine (6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine) and
      metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1
      methylethyl)acetamide] have been found with increasing occurrence in rivers and
      streams. Their continued use will require changes in agricultural practices. We
      compared water quality from four crop-tillage treatments: (i) conventional
      moldboard plow (MB), (ii) MB with ryegrass (Lolium multiflorum Lam.) intercrop
      (IC), (iii) soil saver (SS), and (iv) SS + IC; and two drainage control
      treatments, drained (D) and controlled drainage-subirrigation (CDS). Atrazine
      (1.1 kg a.i. ha-1), metribuzin [4-amino-6-(1,1-dimethylethyl)-3-(methylthio)
      1,2,4-triazine-5(4H)-one] (0.5 kg a.i. ha-1), and metolachlor (1.68 kg a.i. ha-1)
      were applied preemergence in a band over seeded corn (Zea mays L.) rows.
      Herbicide concentration and losses were monitored from 1992 to spring 1995.
      Annual herbicide losses ranged from < 0.3 to 2.7% of application. Crop-tillage
      treatment influenced herbicide loss in 1992 but not in 1993 or 1994, whereas CDS
      affected partitioning of losses in most years. In 1992, SS + IC reduced herbicide
      loss in tile drains and surface runoff by 46 to 49% compared with MB. The
      intercrop reduced surface runoff, which reduced herbicide transport. Controlled
      drainage-subirrigation increased herbicide loss in surface runoff but decreased
      loss through tile drainage so that total herbicide loss did not differ between
      drainage treatments. Desethyl atrazine [6-chloro-N-(1-methylethyl)-1,3,5-triazine
      2,4-diamine] comprised 7 to 39% of the total triazine loss.

PMID- 11285919
TI  - Detailed characterization of solute transport in a heterogeneous field soil.
AB  - There is a necessity for improved physical understanding of solute transport
      processes in heterogeneous soil systems. In situ nondestructive techniques like
      time domain reflectometry (TDR) and fiber optic miniprobes (FOMPs) permit the
      collection of unique measurements of solute transport processes in soils for the
      purposes of model development and validation. This study examined the application
      of TDR and FOMPs to measure solute transport at various points laterally and at
      two depths in a heterogeneous clay-loam soil. A miscible displacement experiment
      was performed at a constant irrigation flux to examine the applicability of these
      probes to field soils. In their first application to a field soil, the FOMPs were
      successfully calibrated and performed well in measuring solute breakthrough
      curves. Two flow regimes were identified in the soil profile, the first where
      lateral spreading of the solute occurred in the surface horizon, followed by
      convergence into preferential flow pathways in the second transport zone. The
      measured transport response was heterogeneous with at least two identifiable
      vertical flow phases. It was demonstrated using transfer function modeling and
      data from a corresponding laboratory study that the FOMPs were measuring the
      slower phase, while the TDR probes captured a composite of the fast and slow
      phases. The combination of these two techniques may be a means to separate solute
      transport phases in heterogeneous media and relate laboratory column results to
      field studies.

PMID- 11285920
TI  - SOIL-SOILN simulations of water drainage and nitrate nitrogen transport from soil
      core lysimeters.
AB  - Water resources protection from nitrate nitrogen (NO3-N) contamination is an
      important public concern and a major national environmental issue. The abilities
      of the SOIL-SOILN model to simulate water drainage and nitrate N fluxes from
      orchardgrass (Dactylis glomerata L.) were evaluated using data from a 3-yr field
      experiment. The soil is classified as a Hagerstown silt loam soil (fine, mixed,
      semiactive, mesic Typic Hapludalf). Nitrate losses below the 1-m depth from N
      fertilized grazed orchardgrass were measured with intact soil core lysimeters.
      Five N-fertilizer treatments consisted of a control, urine application in the
      spring, urine application in the summer, urine application in the fall, and feces
      application in the summer. The SOIL-SOILN models were evaluated using water
      drainage and nitrate flux data for 1993-1994, 1994-1995, and 1995-1996. The N
      rate constants from a similar experiment with inorganic fertilizer and manure
      treatments under corn (Zea mays L.) were used to evaluate the SOILN model under
      orchardgrass sod. Results indicated that the SOIL model accurately simulated
      water drainage for all three years. The SOILN model adequately predicted nitrate
      losses for three urine treatments in each year and a control treatment in 1994
      1995. However, it failed to produce accurate simulations for two control
      treatments in 1993-1994 and 1995-1996, and feces treatments in all three years.
      The inaccuracy in the simulation results for the control and feces treatments
      seems to be related to an inadequate modeling of N transformation processes. In
      general, the results demonstrate the potential of the SOILN model to predict NO3
      N fluxes under pasture conditions using N transformation rate constants
      determined through the calibration process from corn fields on similar soils.

PMID- 11285921
TI  - Particulate phosphorus and sediment in surface runoff and drainflow from clayey
      soils.
AB  - Recent work has shown that a significant portion of the total loss of phosphorus
      (P) from agricultural soils may occur via subsurface drainflow. The aim of this
      study was to compare the concentrations of different P forms in surface and
      subsurface runoff, and to assess the potential algal availability of particulate
      phosphorus (PP) in runoff waters. The material consisted of 91 water-sample pairs
      (surface runoff vs. subsurface drainage waters) from two artificially drained
      clayey soils (a Typic Cryaquept and an Aeric Cryaquept) and was analyzed for
      total suspended solids (TSS), total phosphorus (TP), dissolved molybdate-reactive
      phosphorus (DRP), and anion exchange resin-extractable phosphorus (AER-P). On the
      basis of these determinations, we calculated the concentrations of PP, desorbable
      particulate phosphorus (PPi), and particulate unavailable (nondesorbable)
      phosphorus (PUP). Some water samples and the soils were also analyzed for 137Cs
      activity and particle-size distribution. The major P fraction in the waters
      studied was PP and, on average, only 7% of it was desorbable by AER. However, a
      mean of 47% of potentially bioavailable P (AER-P) consisted of PPi. The suspended
      soil material carried by drainflow contained as much PPi (47-79 mg kg-1) as did
      the surface runoff sediment (45-82 mg kg-1). The runoff sediments were enriched
      in clay-sized particles and 137Cs by a factor of about two relative to the
      surface soils. Our results show that desorbable PP derived from topsoil may be as
      important a contributor to potentially algal-available P as DRP in both surface
      and subsurface runoff from clayey soils.

PMID- 11285922
TI  - Influence of fly ash on soil physical properties and turfgrass establishment.
AB  - A field study (1993-96) assessed the benefits of applying unusually high rates of
      coal fly ash as a soil amendment to enhance water retention of soils without
      adversely affecting growth and marketability of the turf species, centipedegrass
      [Eremochloa ophiuroides (Munro) Hack.]. A Latin Square plot design was employed
      that included 0 (control, no ash applied), 280, 560, and 1120 Mg ha-1 application
      rates of unweathered precipitator fly ash. The fly ash was spread evenly over
      each plot area, rototilled, and allowed to weather under natural conditions for 8
      mo before seeding. High levels of soluble salts, indicated by the electrical
      conductivity (EC) of soil extracts, in tandem with an apparent phytotoxic effect
      from boron (B), apparently inhibited initial plant establishment as shown by
      substantially lower germination counts in treated soil. However, plant height and
      rooting depth were not adversely affected, as were the dry matter (DM) yields
      throughout the study period. Ash treatment did not significantly influence water
      infiltration rate, bulk density, or temperature of the soil, but substantially
      improved water-holding capacity (WHC) and plant-available water (PAW). Enhanced
      water retention capacity improved the cohesion and handling property of harvested
      sod.

PMID- 11285923
TI  - Stabilization of composted organic matter after application to a humus-free sandy
      mining soil.
AB  - The use of mining substrates for recultivation purposes is limited due to their
      low organic matter (OM) contents. In a 1-yr laboratory experiment we evaluated
      the stabilization of biowaste compost added to a humus-free sandy mining soil to
      examine the suitability of compost amendment for the formation of stable soil
      organic matter (SOM). The stabilization process was characterized by measuring
      enrichment of OM and nitrogen in particle size fractions obtained after
      dispersion with different amounts of energy (ultrasonication and shaking in
      water), carbon mineralization, and amount of dissolved organic carbon (DOC).
      During the experiment, 17.1% of the organic carbon (OC) was mineralized. Organic
      carbon enrichment in the < 20-micron particle size fraction at the beginning of
      the experiment was in the range of natural soils with similar texture. Within 12
      mo, a distinct OC redistribution from coarse into fine fractions was found with
      both dispersion methods. The accumulation of OC was more pronounced for the size
      separates obtained by ultrasonication, where the carbon distribution between 0.45
      to 20-micron particle size fractions increased from 30% at the beginning to 71%
      at the end of the experiment. Dissolved organic carbon contents ranged between 50
      and 68 g kg-1 OC and decreased during the incubation. In conclusion, the
      exponential decrease of carbon mineralization and the OC enrichment in the fine
      particle size fractions both indicated a distinct OM stabilization in the mining
      soil.

PMID- 11285924
TI  - Fly ash and lime-stabilized biosolid mixtures in mine spoil reclamation:
      simulated weathering.
AB  - The use of large quantities of neutral coal fly ash (NFA) may be facilitated by
      co-application with a lime-stabilized biosolid (LSB) for the reclamation of acid
      mine spoil (AMS). Although NFA may not aid in the mitigation of acid drainage,
      questions concerning the leachability and mineralogy of native and NFA- and LSB
      born metals must be addressed. In this study, the potential long-term influence
      of LSB and NFA on AMS leachate chemistry and trace element mineralogy was
      evaluated using laboratory weathering and selective dissolution techniques. The
      application of LSB at a rate sufficient to neutralize the potential acidity of
      the AMS increased leachate pH from approximately 3 to 7.5 for the duration of the
      study. Fly ash rates (1X, 1.5X, and 2X LSB rate) did not affect leachate pH. The
      dominant electrolytes in all leachates were Ca and SO4, the concentrations of
      which were mirrored by solution electrical conductivity (EC). Leachate
      concentrations of Al, Fe, Mn, K, Cu, Ni, and Zn were significantly reduced by LSB
      application, whereas concentrations of Ca, SO4, Mg, Cl, F, B, and P were
      increased. Nitrate concentrations were not affected by LSB. With the exception of
      leachate B, which increased with increasing NFA rate and was regenerated during
      the weathering study, NFA did not affect leachate composition. Sequential
      selective dissolution indicated a transformation of Co, Cr, Cu, Ni, Pb, and Zn
      into less labile mineral pools with weathering. The results of these evaluations
      suggest that the application of NFA during AMS reclamation would have little
      effect on leachate chemistry or the mineralogy of trace elements. Thus, the high
      volume application of NFA to AMS during reclamation may offer an additional
      opportunity for the use of this combustion by-product.

PMID- 11285925
TI  - Denitrification from a swine lagoon overland flow treatment system at a pasture
      riparian zone interface.
AB  - In manure disposal systems, denitrification is a major pathway for N loss and to
      reduce N transport to surface and ground water. We measured denitrification and
      the changes in soil N pools in a liquid manure disposal system at the interface
      of a pasture and a riparian forest. Liquid swine manure was applied weekly at two
      rates (approximately 800 and 1600 kg N ha-1 yr-1) to triplicate plots of overland
      flow treatment systems with three different vegetation treatments.
      Denitrification (acetylene block technique on intact cores) and soil N pools were
      determined bimonthly for 3 yr. The higher rate of manure application had higher
      denitrification rates and higher soil nitrate. Depth 1 soil (0-6 cm) had higher
      denitrification, nitrate, and ammonium than depth 2 soil (6-12 cm). The
      vegetation treatment consisting of 20 m of grass and 10 m of forest had lower
      denitrification. Denitrification did not vary significantly with position in the
      plot (7, 14, 21, and 28 m downslope), but nitrate decreased in the downslope
      direction while ammonium increased downslope. Denitrification ranged from 4 to
      12% of total N applied in the manure. Denitrification rates were similar to those
      from a nearby dairy manure irrigation site, but were generally a lower percent of
      N applied, especially at the high swine effluent rate. Denitrification rates for
      these soils range from 40 to 200 kg N ha-1 yr-1 for the top 12 cm of soil treated
      with typical liquid manure that is high in ammonium and low in nitrate.

PMID- 11285926
TI  - Correlation of human olfactory responses to airborne concentrations of malodorous
      volatile organic compounds emitted from swine effluent.
AB  - Direct multicomponent analysis of malodorous volatile organic compounds (VOCs)
      present in ambient air samples from 29 swine (Sus scrofa) production facilities
      was used to develop a 19-component artificial swine odor solution that simulated
      olfactory properties of swine effluent. Analyses employing either a human panel
      consisting of 14 subjects or gas chromatography were performed on the air stream
      from an emission chamber to assess human olfactory responses or odorant
      concentration, respectively. Analysis of the olfactory responses using Fisher's
      LSD statistics showed that the subjects were sensitive to changes in air
      concentration of the VOC standard across dilutions differing by approximately
      16%. The effect of chemical synergisms and antagonisms on human olfactory
      response magnitudes was assessed by altering the individual concentration of nine
      compounds in artificial swine odor over a twofold concentration range while
      maintaining the other 18 components at a constant concentration. A synergistic
      olfactory response was observed when the air concentration of acetic acid was
      increased relative to the concentration of other VOC odorants in the standard. An
      antagonistic olfactory response was observed when the air concentration of 4
      ethyl phenol was increased relative to the other VOC odorants in the standard.
      The collective odorant responses for nine major VOCs associated with swine odor
      were used to develop an olfactory prediction model to estimate human odor
      response magnitudes to swine manure odorants through measured air concentrations
      of indicator VOCs. The results of this study show that direct multicomponent
      analysis of VOCs emitted from swine effluent can be applied toward estimating
      perceived odor intensity.

PMID- 11285927
TI  - Functional classification of swine manure management systems based on effluent
      and gas emission characteristics.
AB  - Gaseous emissions from swine (Sus scrofa) manure storage systems represent a
      concern to air quality due to the potential effects of hydrogen sulfide, ammonia,
      methane, and volatile organic compounds on environmental quality and human
      health. The lack of knowledge concerning functional aspects of swine manure
      management systems has been a major obstacle in the development and optimization
      of emission abatement technologies for these point sources. In this study, a
      classification system based on gas emission characteristics and effluent
      concentrations of total phosphorus (P) and total sulfur (S) was devised and
      tested on 29 swine manure management systems in Iowa, Oklahoma, and North
      Carolina in an effort to elucidate functional characteristics of these systems.
      Four swine manure management system classes were identified that differed in
      effluent concentrations of P and S, methane (CH4) emission rate, odor intensity,
      and air concentration of volatile organic compounds (VOCs). Odor intensity and
      the concentration of VOCs in air emitted from swine manure management systems
      were strongly correlated (r2 = 0.88). The concentration of VOC in air samples was
      highest with outdoor swine manure management systems that received a high input
      of volatile solids (Type 2). These systems were also shown to have the highest
      odor intensity levels. The emission rate for VOCs and the odor intensity
      associated with swine manure management systems were inversely correlated with
      CH4 and ammonia (NH3) emission rates. The emission rates of CH4, NH3, and VOCs
      were found to be dependent upon manure loading rate and were indirectly
      influenced by animal numbers.

PMID- 11285928
TI  - Nutrient conversions by photosynthetic bacteria in a concentrated animal feeding
      operation lagoon system.
AB  - A diurnal examination was conducted to determine the effect of photosynthetic
      bacteria on nutrient conversions in a two-stage concentrated animal feeding
      operation (CAFO) lagoon system in west-central Oklahoma. Changes in nutrients,
      microbial populations, and physical parameters were examined at three depths (0,
      1.5, and 3.0 m) every 3 h over a 36-h period. The south lagoon (SL) was anaerobic
      (dissolved oxygen [DO] = 0.09 +/- 0.12 mg/L) while the north lagoon (NL) was
      facultative (DO ranged from 4.0-0.1 mg/L over 36-h period). Negative sulfide
      sulfate (-0.85) and bacteriochlorophyll a (bchl a)-sulfate (-0.83) correlations,
      as well as positive bchl a-sulfide (0.87) and light intensity (I)-bchl a (0.89)
      correlations revealed that the SL was dominated by sulfur conversions driven by
      the photosynthetic purple sulfur bacteria (PSB). The correlation data was
      supported by diurnal trends for sulfate, sulfide, and bchl a. Both nitrogen and
      sulfur conversions played a role in the NL; however, nitrogen conversions
      appeared to dominate this system because of the activity of cyanobacteria. This
      was shown by positive chlorophyll a (chl a)-I (0.91) and chl a-nitrate (0.98)
      correlations and the negative correlation between ammonium and nitrite (-0.88).
      Correlation data was further supported by diurnal trends observed for chl a, DO,
      and ammonium. For both lagoons, the dominant photosynthetic microbial species
      determined which nutrient conversion processes were most important.

PMID- 11285929
TI  - Hydrologic behavior of two engineered barriers following extreme wetting.
AB  - Many engineered barriers are expected to function for hundreds of years or
      longer. Over the course of time, it is likely that some barriers will experience
      infiltration to the point of breakthrough. This study compares the recovery from
      breakthrough of two storage-evapotranspiration type engineered barriers.
      Replicates of test plots comprising thick soil and capillary-biobarrier covers
      were wetted to breakthrough in 1997. Test plots were kept cleared of vegetation
      to maximize hydrologic stress during recovery. Following cessation of drainage
      resulting from the wetting irrigations, water storage levels in all plots were at
      elevated levels compared with pre-irrigation levels. As a result, infiltration of
      melting snow during the subsequent spring overloaded the storage capacity and
      produced drainage in all plots. Relatively rapid melting of accumulated snowfall
      produced the most significant infiltration events each year during the study.
      Capillary barriers yielded less total drainage than thick soil barriers. By
      limiting drainage, capillary barriers increased water storage in the upper
      portions of the test plots, which led to increased evaporation from the capillary
      barrier plots compared with thick soil plots. Increased evaporation in the
      capillary barrier plots allowed more water to infiltrate in the second season
      following the wetting tests without triggering drainage. All thick soil plots
      again yielded drainage in the second season. Within two years of intentionally
      induced breakthrough, evaporation alone (without transpiration) restored the
      capability of the capillary barrier covers to function as intended, although
      water storage in these covers remained at elevated levels.

PMID- 11285930
TI  - Hydrologic influence on stability of organic phosphorus in wetland detritus.
AB  - Accretion of organic matter in wetlands provides long-term storage for nutrients
      and other contaminants. Water-table fluctuations and resulting alternate flooded
      and drained conditions may substantially alter the stability of stored materials
      including phosphorus (P). To study the effects of hydrologic fluctuation on P
      mobilization in wetlands, recently accreted detrial material (derived primarily
      from Typha spp.) was collected from the Everglades Nutrient Removal Project
      (ENRP), a constructed wetland used to treat agricultural drainage water in the
      northern Everglades. The detrital material was subjected to different periods of
      drawdown and consecutive reflooding under laboratory conditions. The 31P nuclear
      magnetic resonance (31P NMR) spectroscopy analysis revealed that sugar phosphate,
      glycerophosphate, polynucleotides, and phospholipids (glycerophosphoethanolamine
      and glycerophosphocholine) were the major forms of P in the detrital material.
      After 30 d of drawdown, polynucleotides were reduced to trace levels, whereas
      sugar phosphate, glycerophosphate, and phospholipids remained the major fractions
      of organic P. Microorganisms seemed to preferentially utilize nucleic acid P,
      perhaps to obtain associated nutrients including carbon and nitrogen. At the end
      of the 30-d reflooding period, cumulative P flux from detritus to water column
      accounted for 3% of the total P (< or = 15 d of drawdown) and further decreased
      to 2% at 30 d of drawdown, but increased to 8% at 60 d of drawdown. The drawdown
      (< or = 30 d) not only reduced P flux to the water column, but also increased the
      humification and microbial immobilization of P. Excessive drawdown (60 d),
      however, triggered the release of P into the water column as the water content of
      detritus decreased from 95 to 11%.

PMID- 11285931
TI  - Evaluating non-equilibrium solute transport in small soil columns.
AB  - Displacement studies on leaching of bromide and two pesticides (atrazine and
      isoproturon) were conducted under unsaturated steady state flow conditions in 24
      small undisturbed soil columns (5.7 cm in diameter and 10 cm long) each collected
      from two sites differing in soil structure and organic carbon content in North
      Germany. There were large and irregular variabilities in the characteristics of
      both soils, as well as in the shapes of breakthrough curves (BTCs) of different
      columns, including some with early breakthrough and increased tailing,
      qualitatively indicating the presence of preferential flow. It was estimated that
      one preferential flow column (PFC) at site A, and four at site B, contributed,
      respectively to 11% and 58% of the accumulated leached fraction and to more than
      80% of the maximum observed standard deviation (SD) in the field-scale
      concentration and mass flux of pesticides at two sites. The bromide BTCs of two
      sites were analyzed with the equilibrium convection-dispersion equation (CDE) and
      a non-equilibrium two-region/mobile-immobile model. Transport parameters of these
      models for individual BTCs were determined using a curve fitting program, CXTFIT,
      and by the time moment method. For the CDE based equilibrium model, the mean
      values of retardation factor, R, considered separately for all columns, PFCs or
      non-preferential flow columns (NPFCs) were comparable for the two methods;
      significant differences were observed in the values of dispersion coefficients of
      two sites using the two estimation methods. It was inferred from the estimated
      parameters of non-equilibrium model that 5-12% of water at site A, and 12% at
      site B, was immobile during displacement in NPFCs. The corresponding values for
      PFCs of two sites were much larger, ranging from 25% to 51% by CXTFIT and from
      24% to 72% by the moment method, suggesting the role of certain mechanisms other
      than immobile water in higher degrees of non-equilibrium in these columns. Peclet
      numbers in PFCs of both sites were consistently smaller than five, indicating the
      inadequacy of the non-equilibrium model to incorporate the effect of all forms of
      non-equilibrium in PFCs. Overall, the BTCs of individual NPFCs, PFCs and of field
      average concentration at the two sites were better reproduced with parameters
      obtained from CXTFIT than by the moment method. The moment method failed to
      capture the peak concentrations in PFCs, but tended to describe the desorption
      and tail branches of BTCs better than the curve fitting approach.

PMID- 11285932
TI  - On the behavior of approaches to simulate reactive transport.
AB  - Two families of approaches exist to simulate reactive transport in groundwater:
      The Direct Substitution Approach (DSA), based on Newton-Raphson and the Picard or
      Sequential Iteration Approach (SIA). We applied basic versions of both methods to
      several test cases and compared both computational demands and quality of the
      solution for varying grid size. Results showed that the behavior of the two
      approaches is sensitive to both grid size and chemistry. As a general rule, the
      DSA is more robust than the SIA, in the sense that its convergence is less
      sensitive to time step size (any approach will converge given a sufficiently
      small time step). Moreover, the DSA leads to a better simulation of sharp fronts,
      which can only be reproduced with fine grids after many iterations when the SIA
      is used. As a consequence, the DSA runs faster than SIA in chemically difficult
      cases (i.e., highly non-linear and/or very retarded), because the SIA may require
      very small time steps to converge. On the other hand, the size of the system of
      equations is much larger for the DSA than for the SIA, so that its CPU time and
      memory requirements tend to be less favorable with increasing grid size. As a
      result, the SIA may become faster than the DSA for very large, chemically simple
      problems. The use of an iterative linear solver for the DSA makes its CPU time
      less sensitive to grid size.

PMID- 11285933
TI  - A model of oscillatory transport in granular soils, with application to
      barometric pumping and earth tides.
AB  - A simple algebraic model is proposed to estimate the transport of a volatile or
      soluble chemical caused by oscillatory flow of fluid in a porous medium. The
      model is applied to the barometric pumping of vapors in the vadose zone, and to
      the transport of dissolved species by earth tides in an aquifer. In the model,
      the fluid moves sinusoidally with time in the porosity of the soil. The chemical
      concentration in the mobile fluid is considered to equilibrate with the
      concentration in the surrounding matrix according to a characteristic time
      governed by diffusion, sorption, or other rate processes. The model provides a
      closed form solution, to which barometric pressure data are applied in an example
      of pore gas motion in the vadose zone. The model predicts that the additional
      diffusivity due barometric pumping in an unfractured vadose zone would be
      comparable to the diffusivity in stagnant pore gas if the equilibration time is 1
      day or longer. Water motion due to the M2 lunar tide is examined as an example of
      oscillatory transport in an aquifer. It is shown that the tidal motion of the
      water in an aquifer might significantly increase the vertical diffusivity of
      dissolved species when compared to diffusion in an absolutely stagnant aquifer,
      but the hydrodynamic dispersivity due to tidal motion or gravitational flow would
      probably exceed the diffusivity due to oscillatory advection.

PMID- 11285934
TI  - Modeling solute diffusion in the presence of pore-scale heterogeneity: method
      development and an application to the Culebra dolomite member of the Rustler
      Formation, New Mexico, USA.
AB  - Previous studies have revealed the presence of pore-scale variability in
      diffusivity in the Culebra (dolomite) member of the Rustler Formation, NM. In
      this study, eight laboratory-scale diffusion experiments on five Culebra samples
      were analyzed using a methodology for modeling solute diffusion through porous
      media in the presence of multiple matrix diffusivities, Dp. A lognormal
      distribution of Dp is assumed within each of the lab samples. The estimated
      standard deviation (sigma d) of ln(Dp) within each sample ranges from 0 to 1,
      with most values lying between 0.5 and 1. The variability over all samples leads
      to a combined sigma d in the range of 1.0-1.2, which is consistent with the
      distribution of independently determined formation factor measurements for
      similar Culebra samples. A comparison of our estimation results to other rock
      properties suggests that, at the lab-scale, the geometric mean of Dp increases
      with bulk porosity and the quantity of macroscopic features such as vugs and
      fractures. However, sigma d appears to be determined by variability within such
      macroscopic features and/or by micropore-scale heterogeneity. In addition,
      comparison of these experiments to those at larger spatial scales suggests that
      increasing sample volume results in an increase in sigma d.

PMID- 11285935
TI  - On the selection of primary variables in numerical formulation for modeling
      multiphase flow in porous media.
AB  - Selecting the proper primary variables is a critical step in efficiently modeling
      the highly nonlinear problem of multiphase subsurface flow in a heterogeneous
      porous-fractured media. Current simulation and ground modeling techniques consist
      of (1) spatial discretization of mass and/or heat conservation equations using
      finite difference or finite element methods; (2) fully implicit time
      discretization; (3) solving the nonlinear, discrete algebraic equations using a
      Newton iterative scheme. Previous modeling efforts indicate that the choice of
      primary variables for a Newton iteration not only impacts computational
      performance of a numerical code, but may also determine the feasibility of a
      numerical modeling study in many field applications. This paper presents an
      analysis and general recommendations for selecting primary variables in
      simulating multiphase, subsurface flow for one-active phase (Richards' equation),
      two-phase (gas and liquid) and three-phase (gas, water and nonaqueous phase
      liquid or NAPL) conditions. In many cases, a dynamic variable switching or
      variable substitution scheme may have to be used in order to achieve optimal
      numerical performance and robustness. The selection of primary variables depends
      in general on the sensitivity of the system of equations to the variables
      selected at given phase and flow conditions. We will present a series of
      numerical tests and large-scale field simulation examples, including modeling one
      (active)-phase, two-phase and three-phase flow problems in multi-dimensional,
      porous-fractured subsurface systems.

PMID- 11285936
TI  - Temporal changes in kerosene content and composition in field soil as a result of
      leaching.
AB  - A field experiment was designed to determine the combined effect of leaching and
      natural attenuation on the redistribution dynamics of kerosene--a volatile
      petroleum hydrocarbon mixture (VPHM)--and of its selected individual components
      in the soil subsurface. Variables included the composition of contaminant
      spilled, the soil water content before contamination and the leaching pattern.
      Temporal changes in the residual kerosene concentration and composition in the
      soil subsurface of the experimental field during 39 days and leaching by 500 mm
      of irrigation water were determined to a depth of 100 cm. The main processes
      controlling contaminant attenuation were volatilization and redistribution with
      depth. Soil hydration status was found to affect the attenuation, redistribution
      and composition of VPHM in the porous media. An initial relative increase of n
      alkanes in the subsurface compared with the total VPHM in the first leaching
      period was a result of the volatilization of low vapor pressure compounds. The
      redistribution of individual components in the soil profile during leaching was
      in accordance with their physico-chemical properties.

PMID- 11285937
TI  - Surfactant enhanced recovery of tetrachloroethylene from a porous medium
      containing low permeability lenses. 1. Experimental studies.
AB  - A matrix of batch, column and two-dimensional (2-D) box experiments was conducted
      to investigate the coupled effects of rate-limited solubilization and layering on
      the entrapment and subsequent recovery of a representative dense NAPL,
      tetrachloroethylene (PCE), during surfactant flushing. Batch experiments were
      performed to determine the equilibrium solubilization capacity of the surfactant,
      polyoxyethylene (20) sorbitan monooleate (Tween 80), and to measure fluid
      viscosity, density and interfacial tension. Results of one-dimensional column
      studies indicated that micellar solubilization of residual PCE was rate-limited
      at Darcy velocities ranging from 0.8 to 8.2 cm/h and during periods of flow
      interruption. Effluent concentration data were used to develop effective mass
      transfer coefficient (Ke) expressions that were dependent upon the Darcy velocity
      and duration of flow interruption. To simulate subsurface heterogeneity, 2-D
      boxes were packed with layers of F-70 Ottawa sand and Wurtsmith aquifer material
      within 20-30 mesh Ottawa sand. A 4% Tween 80 solution was then flushed through
      PCE-contaminated boxes at several flow velocities, with periods of flow
      interruption. Effluent concentration data and visual observations indicated that
      both rate-limited solubilization and pooling of PCE above the fine layers reduced
      PCE recovery to levels below those anticipated from batch and column
      measurements. These experimental results demonstrate the potential impact of both
      mass transfer limitations and subsurface layering on the recovery of PCE during
      surfactant enhanced aquifer remediation.

PMID- 11285938
TI  - Surfactant enhanced recovery of tetrachloroethylene from a porous medium
      containing low permeability lenses. 2. Numerical simulation.
AB  - A numerical model of surfactant enhanced solubilization was developed and applied
      to the simulation of nonaqueous phase liquid recovery in two-dimensional
      heterogeneous laboratory sand tank systems. Model parameters were derived from
      independent, small-scale, batch and column experiments. These parameters included
      viscosity, density, solubilization capacity, surfactant sorption, interfacial
      tension, permeability, capillary retention functions, and interphase mass
      transfer correlations. Model predictive capability was assessed for the
      evaluation of the micellar solubilization of tetrachloroethylene (PCE) in the two
      dimensional systems. Predicted effluent concentrations and mass recovery agreed
      reasonably well with measured values. Accurate prediction of enhanced
      solubilization behavior in the sand tanks was found to require the incorporation
      of pore-scale, system-dependent, interphase mass transfer limitations, including
      an explicit representation of specific interfacial contact area. Predicted
      effluent concentrations and mass recovery were also found to depend strongly upon
      the initial NAPL entrapment configuration. Numerical results collectively
      indicate that enhanced solubilization processes in heterogeneous, laboratory sand
      tank systems can be successfully simulated using independently measured soil
      parameters and column-measured mass transfer coefficients, provided that
      permeability and NAPL distributions are accurately known. This implies that the
      accuracy of model predictions at the field scale will be constrained by our
      ability to quantify soil heterogeneity and NAPL distribution.

PMID- 11285939
TI  - Preoperative assessment of coagulation disorders.

PMID- 11285940
TI  - Continuous renal replacement therapy.

PMID- 11285941
TI  - The controversy of "renal-dose dopamine".

PMID- 11285942
TI  - Thrombocytopenia.

PMID- 11285943
TI  - Thromboelastography: where is it and where is it heading?

PMID- 11285944
TI  - Spinal and epidural anesthesia and anticoagulation.

PMID- 11285945
TI  - Ventilatory management of patients with severe asthma.

PMID- 11285946
TI  - Abdominal compartment syndrome.

PMID- 11285947
TI  - Perioperative acute renal failure.

PMID- 11285948
TI  - Standard setting for laparoscopic resection of colorectal cancer.

PMID- 11285949
TI  - Laparotomy, laparoscopy, cancer, and beyond.
AB  - The fate of laparoscopic methods for the treatment of cancer remains uncertain.
      Published middle-range oncologic results from nonrandomized studies demonstrate
      that laparoscopic methods are associated with an outcome comparable with results
      after open resection. The world awaits the 3- and 5-year oncologic results of the
      ongoing randomized and prospective trials. There is a possibility that
      laparoscopic methods may be associated with a survival benefit. Port tumors
      remain a concern. However, results at this writing suggest that these recurrences
      take place at a frequency similar to that of incisional recurrences following
      open cancer resection. Port tumors currently are viewed as local recurrences.
      Traumatization of the tumor at the time of resection is thought to be the most
      important surgery-related risk factor. The demonstration of a survival benefit in
      a randomized trial would likely have a tremendous impact on the surgical world.
      Avoidance of laparotomy-related immunosuppression and tumor stimulation, both of
      which have been well demonstrated in animal studies, theoretically, might account
      for differences in cancer outcome. The early postoperative period may be a
      critical time during which the fate of many cancer patients is determined. It is
      possible that this may be an ideal time frame for antitumor immunotherapy because
      the tumor burden is at its lowest, and because immunotherapy, unlike conventional
      chemotherapy, is unlikely to have a negative impact on wound and anastomotic
      healing. Perioperative nonspecific upregulation of immune function via
      pharmacologic means may improve long-term oncologic results. Similarly,
      preoperative tumor vaccines might provide patients with a specific means of
      combating any remaining tumor cells after curative resection. The results of
      several recently completed murine studies support both of these ideas. Finally,
      early postoperative administration of monoclonal antitumor antibodies might
      provide patients with specific means of combating any remaining tumor cells after
      curative resection. The introduction of advanced minimally invasive techniques
      nearly a decade ago has led to new methods of approaching malignant tumors that
      have the potential to have an impact on the oncologic outcome of cancer patients.
      This decade-long journey also has led to new insights regarding the impact of
      surgery on the patient. It also has alerted us concerning the importance of the
      immediate postoperative period in the patient's ongoing struggle against the
      tumor. These insights hopefully will lead to better surgical methods and new
      perioperative adjuvant therapies that will increase the rate of survival and
      reduce the recurrence rates for cancer patients.

PMID- 11285950
TI  - Experience as a factor influencing the indications for laparoscopic colorectal
      surgery and the results.
AB  - BACKGROUND: The influence of experience on the results of treatment with
      laparoscopic surgery is indisputable. The establishment of indications and
      contraindications is relative, and varies depending on the experience of the
      surgeon. Learning curves have been described for a number of laparoscopic
      interventions, in particular laparoscopic cholecystectomy. The current
      prospective multicenter study investigates, among other things, the interrelation
      between experience and the results of treatment using laparoscopic colorectal
      surgery. The study makes no pronouncements on the long-term results achieved in
      patients with colorectal carcinoma who underwent an operation with curative
      intent, although relevant data were indeed collected. RESULTS: Between August 1,
      1995 and February 1, 1999, a total of 1,658 patients were recruited to the
      prospective multicenter study initiated by the Laparoscopic Colorectal Surgery
      Study Group. To investigate the influence of surgical experience, two groups were
      formed. Group A comprised all the institutions and surgeons with experience of
      more than 100 laparoscopic colorectal operations. Group B contained institutions
      and surgeons with experience of fewer than 100 such interventions. The results of
      this study clearly show that in Group A, significantly more procedures involving
      the rectum were performed (26.7% vs 9.5%), and significantly more carcinomas were
      surgically managed (37.3% vs 17.3%). Despite this significantly higher level of
      technically difficult procedures in the patient population of group A, which was
      comparable in terms of age, gender, height, and weight with the patient in group
      B, the postoperative mortality and morbidity was, with the exception of urinary
      tract infections, identical between the two groups. Conversion to open surgery
      was significantly less frequent in group A (4.3% vs 6.9%), and, finally, the
      duration of the procedures performed by the more experienced surgeons of group A
      was appreciably shorter than in institutions with a smaller frequency of such
      operations. CONCLUSIONS: Laparoscopic colorectal surgery is very demanding, and
      can be performed with low morbidity and mortality rates only by a surgeon with
      above-average experience with this type of surgery and a large caseload of
      laparoscopic colorectal procedures. The learning curve for such procedures is
      appreciably longer than for other laparoscopic operations. With increasing
      experience, technically more demanding operations, including radical oncologic
      rectal laparoscopic procedures, can be performed with appreciably reduced
      operating times and conversion rates, but with no increase in morbidity or
      mortality.

PMID- 11285951
TI  - Efficacy of surgical measures in preventing port-site recurrences in a porcine
      model.
AB  - BACKGROUND: Port-site recurrences are serious complications of laparoscopy
      performed for cancer. Incidences reported in the literature vary between 0% and
      21%, suggesting an influence of the surgeon. METHODS: The aim of this
      experimental, prospective, randomized, single-blind study was to investigate the
      influence that the quality surgery has on the incidence of port-site recurrences.
      After a 12-mmHg carbon dioxide (CO2) pneumoperitoneum was created, 10(7) human
      HeLa cell were injected into the peritoneal cavity of 18 pigs, creating a
      xenogeneic tumor. Laparoscopic sigmoid resections then were performed using four
      trocars and a transanal double-stapling technique. The following protective
      measures were applied in nine animals: trocar fixation, prevention of gas leaks,
      rinsing of instruments with povidone-iodine, minilaparotomy protection, rinsing
      of trocars before removal, peritoneal closure, and rinsing of all wounds with
      povidoneiodine. Surgeons and type of procedures were randomized. After 4 weeks,
      the animals were killed and all portsites excised. Blinded immunohistologic
      analysis with antihuman pancytokeratin antibody was performed. RESULTS: Tumor
      recurrence was present in 23 of 36 port sites (63.8%) in the control group, but
      only in 5 of 36 port sites (13.8%) in the group that received protective measures
      (p = 0.002; Fisher's exact test). No peritoneal carcinosis nor anastomotic
      recurrences were observed. CONCLUSION: These results strongly suggest that the
      quality of surgical technique has an influence on the incidence of port-site
      recurrences. From now on, we propose to use these protective measures routinely
      in cancer laparoscopy.

PMID- 11285952
TI  - Endoscopic clipping in video-assisted thoracoscopic sympathetic blockade for
      axillary hyperhidrosis. An analysis of 26 cases.
AB  - BACKGROUND: Endoscopic thoracic sympathectomy or sympathicotomy is the standard
      method for the treatment of axillary hyperhidrosis. But postoperative
      compensatory sweating may be troublesome in some patients. Therefore, we use
      endoclips to perform the T3 and T4 sympathetic blockade instead of permanently
      interrupting the transmission of nerve impulses from the sympathetic trunk.
      METHODS: Between May 1997 and June 1998, a total of 26 patients with axillary
      hyperhidrosis underwent video-assisted thoracoscopic sympathetic blocking of the
      T3 and T4 ganglia at our hospital. There were 10 men and 16 women with a mean age
      of 31.7 years (range, 16-47). All patients were placed in a semi-sitting position
      under single-lumen intubated anesthesia. We performed the sympathetic blockade by
      clipping the T3 and T4 ganglia at the level of the third, fourth, and fifth rib
      beds using an 8-mm 0 degree thoracoscope. RESULTS: Bilateral T3 and T4
      sympathetic blockade was achieved in all 26 patients. The operation was usually
      completed within 30 min (range, 20-42). Most patients were discharged within 4 h
      after the operation. Surgical complications were minimal, with only one case of
      segmental atelectasis (3.8%). There were no deaths. The mean postoperative follow
      up period was 31.3 months (range, 24-37). Twenty-three patients (88.5%) developed
      compensatory sweating of the trunk and lower limbs. Twenty-four patients (92.3%)
      were satisfied with the results of the operation. Improvement of axillary
      hyperhidrosis was obtained in all patients. One patient underwent a reverse
      operation to remove the endoclips due to intolerable compensatory sweating;
      improvement was seen 25 days after removal of the clips. CONCLUSION: Video
      assisted thoracoscopic T3 and T4 sympathetic blockade by clipping is a safe and
      effective method for the treatment of patients with axillary hyperhidrosis.
      Patients who experience excessive compensatory sweating may require a reverse
      operation for endoclip removal.

PMID- 11285953
TI  - Thoracoscopic splanchnicectomy for control of intractable pain due to advanced
      pancreatic cancer.
AB  - BACKGROUND: Severe upper abdominal pain is a dominant and distressing feature of
      advanced pancreatic cancer. This study was performed to evaluate pain intensity
      and to determine the ways in which pain may interfere with the common daily
      activities of patients with intractable pain before and after thoracoscopic
      splanchnicectomy. METHODS: Twenty-six left-sided thoracoscopic splanchnicectomies
      were performed. To assess pain severity and the impact of pain, all patients
      completed a short questionnaire using the 0-10 Numeric Rating Scale. The Pain
      Management Index was used to describe and compare the adequacy of analgesic
      management. Patients were evaluated 1 day prior to operation and for 6 months
      after the procedure. RESULTS: Pain was reduced significantly after the operation
      (p < 0.001), and all patients enjoyed consistent pain relief during the
      postoperative follow-up. The degree to which pain interfered with their daily
      function decreased significantly (p < 0.001) after surgery. The adequacy of the
      analgesic management improved, and none of the patients required opioids.
      CONCLUSIONS: Unilateral left thoracoscopic splanchnicectomy is a simple,
      minimally invasive, effective, and safe procedure that can be recommended as the
      method of choice for the management of intractable upper abdominal pain due to
      advanced pancreatic cancer.

PMID- 11285954
TI  - Resolution of chronic medical conditions after laparoscopic adjustable silicone
      gastric banding for the treatment of morbid obesity in the elderly.
AB  - BACKGROUND: The routine cutoff age of surgery for morbid obesity is 55 years. A
      minimally invasive surgical approach, however, may enable its safe use in older
      individuals. METHODS: Laparoscopic adjustable silicon gastric banding (LASGB) was
      performed in 18 patients 60 years or older. The perioperative course, early and
      late complications, and long-term follow-up all were recorded. RESULTS: Of 398
      patients who underwent LASBG until November 1998 (mean age, 38.1 years), 18 were
      60 years or older (mean, 63.6 years). The mean body mass index (BMI) was 44.4
      (range, 35-64.7). There were no intraoperative complications. However, four
      patients had late complications requiring reoperation. The mean operative time
      was 65 min; the mean hospital stay was 1.3 days; and the mean follow-up period
      was 21.9 months. The BMI dropped from 44.2 to 30.5, and all comorbid conditions
      improved markedly: Diabetes mellitus resolved in 71% of the patients,
      hypertension in 33%, and sleep apnea in 100%. CONCLUSION: According to the
      findings from this study, LASGB is feasible, safe, and effective in the elderly,
      and most benefit from resolution or marked improvement of comorbid conditions.

PMID- 11285955
TI  - Accuracy and effectiveness of laparoscopic vs open hepatic radiofrequency
      ablation.
AB  - BACKGROUND: The purpose of this study was to compare the accuracy (in terms of
      ultrasound-guided probe placement) and the effectiveness (in terms of pathologic
      tumor-free margin) of laparoscopic vs open radiofrequency (RF) ablation. METHODS:
      Using a previously validated tissue-mimic model, 1-cm simulated hepatic tumors
      were ablated in 10 pigs randomized to open or laparoscopic techniques. Energy was
      applied until tissue temperature reached 100 degrees C (warm-up) and thereafter
      for 8 min. A pathologist blinded to technique examined all specimens immediately
      after treatment. Analysis was by Fisher's exact test and the Mann-Whitney U test;
      p < 0.05 was considered significant. RESULTS: Off-center distance (3.5 +/- 1.6 vs
      4.2 +/- 1.4 mm), size (24.7 +/- 3.1 vs 25.6 +/- 3.8 mm), symmetry (40% vs 73%),
      margin positivity (33% vs 9%), and margin distance (1.1 +/- 1.2 vs 2.2 +/- 1.6
      mm) were not significantly different between laparoscopic (n = 15) and open (n =
      11) ablations, respectively. The proportion of round/ovoid lesions (20% vs 64%)
      was lower (p = 0.043), and warm-up time (20.2 +/- 14.0 vs 10.7 +/- 7.5) was
      longer (p = 0.049) for the laparoscopic than for the open groups, respectively.
      CONCLUSION: Accurate probe placement can be achieved using laparoscopic and open
      RF ablation techniques. The physiologic effects of laparoscopy may alter ablation
      shape and warm-up time. Additional studies are needed to establish effective ways
      of achieving complete tumor destruction.

PMID- 11285956
TI  - Radiofrequency interstitial thermal ablation of hepatocellular carcinoma in liver
      cirrhosis. Role of the laparoscopic approach.
AB  - BACKGROUND: The laparoscopic approach to radiofrequency interstitial thermal
      ablation (RITA) of hepatocellular carcinoma (HCC) with intraoperative ultrasound
      guidance has been proposed with the aim of obtaining additional information for a
      better neoplastic staging and a complete and effective treatment of the liver
      lesions in patients with a difficult percutaneous approach. METHODS: In this
      pilot study, 29 patients with HCC in liver cirrhosis were submitted to
      laparoscopic RITA under sonographic guide. Most of these patients were in Child's
      A class of liver function. Patients with large tumors (> 5 cm), portal vein
      thrombosis, or severe liver disease (Child's C class) were excluded from the
      study. RESULTS: The laparoscopic RITA procedure was completed in 27 of 29
      patients (93% feasibility rate). The laparoscopic ultrasound examination
      identified new malignant liver nodules in five patients (18.5%). A total of 44
      lesions were treated. The mean operative time was 75.8 +/- 20.5 min (range, 45
      120 min), and the mean RITA time was 18 +/- 10 min (range, 10-56 min). There was
      no operative mortality, and postoperative morbidity was low (four cases) without
      any mortality. A complete tumor necrosis was observed in 90% of the patients via
      spiral computed tomography (CT) 1 month after treatment. CONCLUSIONS:
      Laparoscopic RITA of hepatocellular carcinoma proved to be a safe and effective
      technique, at least in the short term. Its role in the treatment of HCC needs to
      be defined in larger series.

PMID- 11285957
TI  - Laparoscopic treatment of severe acute pancreatitis.
AB  - BACKGROUND: The appropriate surgical treatment for severe acute pancreatitis has
      been disputed for a long time. Herein we describe our experience with the
      laparoscopic treatment of this disease. METHODS: Ten patients, seven male and
      three female, with an average age of 55 years were diagnosed with severe acute
      pancreatitis. All cases but one were found to be without biliary stones by
      ultrasonic and CT scans. Laparoscopic exploration, irrigation, drainage, and
      decompression of the pancreas were performed. Further treatment, including
      gastric decompression, irrigation via the drainage tubes, antibiotics,
      somatostatin, and parenteral nutrition, was continued in all patients following
      the laparoscopic procedures. RESULTS: Nine patients recovered successfully; one
      died from adult respiratory distress syndrome (ARDS) soon after the operation.
      The hospital stay was 10-30 days. CONCLUSIONS: The laparoscopic era offers new
      hope for the treatment of severe acute pancreatitis. The technique can be used to
      determine the pathologic extent of the disease, to irrigate and drain the
      abdominal cavity, and to decompress the pancreas. Almost every surgical procedure
      for acute pancreatitis can be performed laparoscopically.

PMID- 11285958
TI  - Effect of increased intraabdominal pressure on cardiac output and tissue blood
      flow assessed by color-labeled microspheres in the pig.
AB  - BACKGROUND: Studies of the hemodynamic effects associated with the
      pneumoperitoneum have had controversial results. We set out to investigate the
      effect of increased intraabdominal pressure (IAP) on cardiac output and tissue
      blood flow in various intraabdominal and extraabdominal organs using the color
      labeled microsphere (CLM) technique. METHODS: IAP was induced by CO2 insufflation
      in anesthetized pigs; 0, 5, and 10 mmHg was used in the low-pressure group and 0,
      15, and 24 mmHg in the high-pressure group. Tissue blood flow (ml.min-1.g-1) and
      cardiac output (CO) (ml/min) were determined by the CLM technique. RESULTS: CO
      decreased at IAP > or = 15 mmHg. Arterial PaCO2 and hydrogen ion concentration
      increased in response to all levels of IAP. Arterial PaO2, oxygen saturation, and
      bicarbonate ion concentration remained unchanged. Low IAP did not influence
      tissue blood flows in most of the organs. However, in the spleen, pancreas,
      esophagus, and gastric mucosal specimens, tissue blood flow was significantly
      decreased at 24 mmHg. CONCLUSION: The level of IAP used in current practice (10
      12 mmHg) appears to be safe with regard to hemodynamic variables and tissues
      blood flow; however, higher levels may induce a decrease in cardiac output and
      tissue blood flow.

PMID- 11285959
TI  - Laparoscopic adrenalectomy in children.
AB  - BACKGROUND: The aim of this study was to describe the indications and results of
      laparoscopic adrenalectomy in children. METHODS: This retrospective multicenter
      study included six children (four boys, two girls) aged 2-16 years (mean, 9.5).
      Three children had hypertension. In three cases, the adrenal mass was discovered
      incidentally. The tumors were bilateral in two children, right-sided in two
      cases, and left-sided in two cases. The mean tumor size was 4 cm (range, 1-7).
      Each child underwent MIBG scintigraphy and MRI before the operation. RESULTS:
      Four right and two left adrenal glands were resected by laparoscopy
      (transperitoneal), and two left glands were resected by retroperitoneoscopy. Two
      conversions were necessary for two left adrenal glands (one retroperitoneoscopy,
      one laparoscopy). Two partial resections and six adrenalectomies were performed.
      Histological examination of the tumors revealed two ganglioneuromas, one
      neuroblastoma, and five pheochromocytomas (two bilateral). One child had an
      involved node (pheochromocytoma). Both bilateral pheochromocytomas had von Hippel
      Lindau disease. There was no morbidity. Mean hospitalstay was 6 days.
      Postoperative evaluation at 1 month was normal in all children. CONCLUSION: The
      indications for laparoscopic adrenalectomy in children are benign tumors and
      pheochromocytomas. In these cases, laparoscopic adrenalectomy is feasible and
      safe, even in cases of pheochromocytoma.

PMID- 11285960
TI  - A critical analysis of intraoperative time utilization in laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Most of the expense of laparoscopic cholecystectomy (LC) is incurred
      while the patient is in the operation room; however, heretofore there has been no
      critical analysis of the time required to perform the various steps of the
      operation. An understanding of how operative time is used is the first step
      toward improving the efficiency of the procedure and decreasing costs while
      maintaining an acceptable standard of care. METHODS: Of 194 patients undergoing
      LC at a university hospital between 1994 and 1997, operational videotapes of 48
      randomly chosen patients were reviewed. Three groups of patients were identified:
      those undergoing LC for chronic cholecystitis (n = 27), those undergoing LC for
      acute cholecystitis (n = 11), and those with common bile duct stones (CBDS), (n =
      10) undergoing LC with transcystic common bile duct exploration. The procedure
      was divided into the following seven steps; trocar entry, laparoscopic
      ultrasound, dissection of the triangle of Calot, cholangiogram, dissection of the
      gallbladder, extraction of the gallbladder, and irrigation-aspiration with
      removal of ports. Time spent for camera cleaning, bleeding control, and insertion
      of the cholangiocatheter into the cystic duct was also calculated. The groups
      were compared in terms of time spent for each step using the Kruskal-Wallis and
      Mann-Whitney U tests. RESULTS: The mean +/- SD operating time was 66.5 +/- 20.5
      min. The acute group had the longest operating time, followed by the CBDS and
      chronic groups. Dissection of the gallbladder, insertion of the
      cholangiocatheter, and irrigation-aspiration were longer steps in the acute group
      than in the other groups (p < 0.05). Dissection of the triangle of Calot took
      longer in acute cholecystitis than in chronic cholecystitis (p < 0.05). CBDS
      cases took longer (p < 0.05) than chronic cases because stone extraction added an
      average of 17.5 min to the time required for the cholangiogram in chronic
      cholecystitis. Laparoscopic ultrasound took longer in the CBDS group than in the
      other groups (p < 0.05). The mean +/- SD time spent for the cholangiogram and
      laparoscopic ultrasound in chronic cholecystitis was 7.5 +/- 4.3 and 4.8 +/- 1.9
      min, respectively. CONCLUSIONS: This time analysis study demonstrates that acute
      cholecystitis requires a longer operating time because most of the individual
      steps in the procedure take longer. In patients with choledocholithiasis, stone
      extraction was responsible for longer operating times. This study should serve as
      a basis for future studies focusing on time utilization in laparoscopic surgery.

PMID- 11285961
TI  - A randomized controlled trial assessing the effect of heated carbon dioxide for
      insufflation on pain and recovery after laparoscopic fundoplication.
AB  - BACKGROUND: Insufflation with heated gas for laparoscopy may reduce postoperative
      pain. This study assessed the effect of heated gas on outcome after
      fundoplication. METHODS: A blinded, randomized trial compared the effect of
      heated or standard carbon dioxide (CO2) on core temperature, postoperative pain,
      analgesic requirement, and postoperative recovery. Pain scores were assessed with
      a 100 mm visual analog scale (VAS). Recovery was assessed with a patient diary
      and clinical follow-up assessment at 8 days and 1 month postoperatively. RESULTS:
      For this study, 40 patients were randomized to heated CO2 (n = 19) and standard
      CO2 (control) (n = 21) groups. The heated CO2 group increased core body
      temperature from 35.9 degrees to 36.1 degrees C, (p = 0.008), whereas the control
      group maintained core temperature at 35.8 degrees C. The control group had lower
      analgesic requirements and pain scores, significant at 12 h (VAS: 20 vs 36 mm; p
      = 0.04). There was no difference between the groups in terms of late recovery.
      The heated CO2 group showed a significant correlation between operative duration
      and requirement for postoperative morphine (p = 0.01). CONCLUSIONS: Heated gas
      provides no benefit for patients and may be associated with increased early pain.
      The elevation of core body temperature observed with heated CO2 is of little
      clinical significance.

PMID- 11285962
TI  - Psychiatric disorders affect outcomes of antireflux operations for
      gastroesophageal reflux disease.
AB  - BACKGROUND: Most of the information used to determine a patient's candidacy for
      antireflux surgery has centered on physiologic measurements of esophageal
      functioning and quantitative assessment of acid reflux. Unfortunately, little
      attention has been paid to the study of psychosocial factors that could affect
      outcomes. The purpose of this study was to establish whether concomitant
      psychiatric disorders might affect the symptomatic outcomes of antireflux
      surgery. METHODS: We retrospectively reviewed a prospectively gathered database
      of patients with gastroesophageal reflux disease (GERD) who underwent either open
      or laparoscopic antireflux surgery. A history of a psychiatric disorder was
      considered to be present if the patient had been previously diagnosed with a DSM
      IV psychiatric diagnosis and was being medically treated for it. Preoperatively,
      patients were evaluated with the symptom severity questionnaire, the GERD-HRQL
      (best score 0, worst score 50). Later in the series, patients were also evaluated
      with the generic quality-of-life questionnaire, the SF-36 (best score 100, worst
      score 0). After antireflux surgery, patients completed both questionnaires 6
      weeks postoperatively. RESULTS: A total of 94 patients underwent antireflux
      surgery. Seventy-seven of them had laparoscopic antireflux surgery (either Nissen
      or Toupet fundoplication), and 17 had open antireflux surgery (Nissen, Toupet,
      Collis-Nissen, or Belsey fundoplications). Nine patients had psychiatric
      disorders (five major depression, four anxiety disorders). At 6-week follow-up,
      95.3% of patients without psychiatric disorders were satisfied with surgery, as
      compared to 11.1% of patients with psychiatric disorders (p < 0.000001). Patients
      satisfied with surgery had a median SF-36 mental health domain score of 76, as
      compared to a score of 36 for patients dissatisfied with surgery (p = 0.0002).
      Patients without psychiatric disorders showed improvement in the median total
      GERD-HRQL score from 27 preoperatively to 1 postoperatively (p < 0.000001),
      whereas patients with psychiatric disorders demonstrated less improvement, from
      30 preoperatively to 10.5 postoperatively (p = 0.03). CONCLUSIONS: Patients with
      psychiatric disorders are rarely satisfied with the results of antireflux
      surgery. Moreover, these patients demonstrated less symptomatic relief than
      patients without psychiatric disorders. Patients who were dissatisfied with
      antireflux surgery--even those without psychiatric disorders--had lower scores on
      the SF-36 mental health domain. These results suggest that even patients who
      might otherwise be candidates for antireflux surgery may have a poor symptomatic
      outcome, if they also have low mental health domain scores. Antireflux surgery in
      patients who suffer from major depression or anxiety disorder should be
      approached with great trepidation.

PMID- 11285963
TI  - Thoracoscopic mobilization of the esophagus. A 6 year experience.
AB  - BACKGROUND: Traditionally, esophageal resection has been performed using a
      thoracotomy to access the intrathoracic esophagus. With the aim to avoid the
      potential morbidity of the open thoracic approach, mobilization of the esophagus
      under direct vision recently has been described. We report our experience at
      attempting thoracoscopic mobilization of the esophagus in 162 patients during a 6
      year period. METHODS: Patients with malignancy or end-stage benign disease of the
      esophagus considered suitable for a three-stage esophagectomy underwent a
      thoracoscopy with a view to endoscopic mobilization of the esophagus. Of the 162
      patients in whom the procedure was attempted, it was abandoned in 9 patients
      (6%), and the procedure was converted to open surgery in 11 patients (7%).
      RESULTS: In the patients whose esophagus was mobilized, the average blood loss
      was 165 ml, and the average time for the thoracoscopic segment of the surgery was
      104 min. In the 133 patients who underwent a resection for invasive malignancy, a
      limited mediastinal nodal dissection retrieved an average of 11 nodes, and the
      median survival was 29 months. The 30-day mortality was 3.3% and the in-hospital
      mortality 5.3%. CONCLUSIONS: Thoracoscopic mobilization can be performed safely
      with satisfactory outcomes in a center performing a large volume of esophageal
      surgery and possessing advanced endoscopic surgery skills. Further assessment of
      this technique and comparisons with traditional open procedures are needed to
      assess this approach further as an appropriate oncologic procedure.

PMID- 11285964
TI  - Pneumoperitoneum upregulates preproendothelin-1 messenger RNA.
AB  - BACKGROUND: Laparoscopic pneumoperitoneum has been shown to decrease glomerular
      filtration rate (GFR) and urine volume (UV). Endothelin-1 (ET-1), a potent renal
      vasoconstrictor, has been implicated. The purpose of this study was to determine
      renal function, ET-1 gene expression, and peptide localization in kidneys
      subjected to CO2 pneumoperitoneum. METHODS: Experiments were performed in three
      groups of anesthetized Sprague-Dawley rats in which GFR and UV were measured
      before, during, and after insufflation. In the first group (n = 8),
      pneumoperitoneum (10 mmHg) was established for 30 min. The second group (n = 4)
      underwent a sham operation without pneumoperitoneum. In the final group (n = 4),
      kidneys were obtained from normal control animals without any prior surgical
      instrumentation. PreproET-1 (ppET-1) mRNA levels were measured by reverse
      transcription-polymerase chain reaction (RT-PCR). The ET-1 peptide was localized
      within kidneys by immunohistochemistry (IHC). RESULTS: Pneumoperitoneum caused a
      significant (p < 0.05) 87% decrease in GFR and a 79% decrease in UV from
      baseline, with a return to baseline values after desufflation. RT-PCR showed a
      significant (p < 0.05) increase in expression of ppET-1 mRNA in the laparoscopic
      group; it was 3.52 +/- 0.33 densitometric units (DU), as compared to 0.35 +/-
      0.06 DU and 0.57 +/- 0.12 DU in the control and sham groups, respectively. IHC
      showed enhanced expression of the ET-1 peptide in the vascular endothelium and
      proximal tubular cells of the laparoscopic group compared to the control and sham
      groups. CONCLUSION: Pneumoperitoneum induces ET-1 gene and peptide upregulation
      in the kidney. Expression of ET-1 is increased in the renal vasculature and
      proximal tubular cells. The elevation of ET-1 and its localization may account
      for some of the renal dysfunction observed during pneumoperitoneum. This suggests
      that antagonism of ET-1 may be beneficial in patients with renal impairment
      undergoing prolonged laparoscopic procedures or in protecting allograft function
      during and after living donor nephrectomy.

PMID- 11285965
TI  - Liver metastasis following pneumoperitoneum with different gases in a mouse
      model.
AB  - BACKGROUND: The validity of using CO2 in laparoscopic tumor surgery has not yet
      been established. To address this question, we investigated the growth of liver
      metastases following insufflation with different gases in a mouse laparoscopy
      model. METHODS: Male BALB/C mice inoculated intraportally with colon 26 cells
      were randomized to undergo pneumoperitoneum with CO2 (n = 16), helium (n = 16),
      argon (n = 16), or air (n = 17), or to act as controls without insufflation (n =
      17). RESULTS: The growth of cancer nodules on the liver 14 days after surgery was
      greater in mice following insufflation with CO2 (p < 0.01), helium (p < 0.01),
      argon (p = 0.01), and air (p = 0.07) than in control mice. No significant
      differences were found between the four insufflation groups in the growth of
      liver metastases. CONCLUSION: These results suggest that insufflation plays an
      important role in the development of liver metastases but that the choice of gas
      may not affect their growth.

PMID- 11285966
TI  - Outpatient laparoscopic cholecystectomy. Outcomes of 847 planned procedures.
AB  - BACKGROUND: Cholecystectomy is now being performed on an outpatient basis at many
      centers. The purpose of this study was to review the results of our large
      experience with this procedure. METHODS: Between 1990 and 1997, 2288 patients
      underwent laparoscopic cholecystectomy at our clinic. A total of 847 (37%) were
      scheduled as outpatients. The selection criteria for planned outpatient
      laparoscopic cholecystectomy called for nonfrail patients with an ASA < 4 who
      were living < 2 h from the hospital. All patients received detailed preoperative
      instruction about outpatient laparoscopic cholecystectomy. A questionnaire was
      sent to 309 patients to sample their opinions. RESULTS: Since 1993, we have
      increased the number of planned outpatient cholecystectomies performed at our
      clinic, but the percentage of cholecystectomies completed on an outpatient basis
      has remained approximately 60%. A total of 547 of 847 operations scheduled as
      outpatient procedures (74.5%) were completed as planned, and 204 patients (24%)
      were kept in the hospital overnight. Twenty-seven (3%) were converted to open
      procedures. Eighteen laparoscopic patients (2%) stayed > 1 day (range, 2-20).
      None of the patients died. Of the 142 patients (46%) who completed our opinion
      survey, 66% were happy with their experience, 32% would like to have stayed in
      the hospital, and 2% were undecided. CONCLUSION: Successful same-day surgery
      requires proper patient instruction, appropriate patient selection, and a low
      threshold to convert patients to inpatient status when the situation warrants. No
      major complications occurred as a result of same-day discharge, and two-thirds of
      the patients said that they preferred outpatient surgery.

PMID- 11285967
TI  - Systemic vs local administration of delta-aminolevulinic acid for laparoscopic
      fluorescence diagnosis of malignant intra-abdominal tumors. Experimental study.
AB  - BACKGROUND: Administration of delta-aminolevulinic acid (ALA) either systemically
      or locally results in tumor-specific accumulation of protoporphyrin IX (PpIX).
      When excited with light at a defined wavelength and viewed with the appropriate
      filter cells containing PpIX, have a characteristic red fluorescence. We
      evaluated both locally (intraperitoneally [i.p.]) and systemically (intravenously
      [i.v.]) administered ALA to compare its effectiveness for laparoscopic
      fluorescent visualization of intraperitoneal tumors. METHODS: Peritoneal
      carcinosis was induced in rats using colon carcinoma cells (CC531).
      Photosensitization was achieved either by intravenous (i.v. group) or
      intraperitoneal (i.p. group) application of ALA solution. Staging laparoscopy was
      performed in both groups, first using conventional white light and subsequently
      using blue light (380-440 nm) to excite PpIX-induced fluorescence. RESULTS:
      Conventional white light laparoscopy showed 142 visible intraperitoneal tumor
      foci in the i.p. group and 116 such foci in the i.v. group. In the i.p. group,
      all tumors (100%) also were fluorescence positive, whereas in the i.v. group only
      32 of the tumors (28%) showed the typical red fluorescence. In the i.p. group, 30
      additional tumors were detected by fluorescence excitation (21%), as compared
      with eight additional tumors in the i.v. group (7%). CONCLUSIONS: Fluorescence
      laparoscopy after local (i.p.) photosensitization with ALA is a more reliable and
      effective method than systemic (i.v.) photosensitization for the detection of
      small or occult i.p. tumors.

PMID- 11285968
TI  - Laparoscopy reduces unnecessary appendicectomies and improves diagnosis in
      fertile women. A randomized study.
AB  - BACKGROUND: The aim of this study was to study the value of diagnostic
      laparoscopy prospectively in fertile women scheduled for acute appendectomy.
      METHODS: For this study, 110 women, with acute abdominal pain ages 15 to 47
      years, in whom the surgeon had decided to perform an appendectomy, were
      randomized to either open appendectomy or diagnostic laparoscopy, then open
      appendectomy if necessary. RESULTS: Appendicitis was diagnosed in 66% of the
      women after open surgery, and in 73% after laparoscopy. During laparoscopy, was
      appendicitis misdiagnosed in only 7% of the women, from whom the appendix
      unnecessarily removed, whereas 34% in the open surgery group had a healthy
      appendix removed. No appendicitis was missed in the laparoscopic group. The
      relative risk of removing a healthy appendix in open surgery was 6.6 relative
      risk (range, 2-21 C.I.) as compared with laparoscopy. Among the women with a
      healthy appendix, a gynecologic diagnosis was found in 73% after laparoscopy, as
      compared with 17% after open surgery. CONCLUSIONS: Laparoscopy reduces
      unnecessary appendectomies and improves diagnosis in fertile women.

PMID- 11285969
TI  - Septic complications of elective laparoscopic colorectal resection.
AB  - BACKGROUND: We set out to determine the rate and pattern of septic complications
      of the surgical wound, abdominal cavity, and urinary and respiratory tracts
      following laparoscopic colorectal resection. METHODS: A longitudinal database of
      500 consecutive cases of colorectal resections was reviewed. RESULTS: The total
      wound infection rate was 7.2% (36/500) and included infections of the abdominal
      wall wounds (32/500, 6.4%) and the perineal wounds (4/50, 8%). The anastomotic
      leak rate in 418 patients who underwent resection with primary anastomosis was
      3.3% (14/418). Intraabdominal abscesses were diagnosed in 1% (5/500) of patients.
      Urinary tract infections were rare (3/500, 0.6%), as was postoperative pneumonia
      (6/500, 1%). CONCLUSIONS: This study confirms the low rate of postoperative
      pneumonia observed with all other minimally invasive procedures. Intraabdominal
      abscesses, urinary tract infections, and postoperative pneumonia occur
      considerably less frequently than in reported historical controls for open
      surgery. The rates of abdominal wound infection and anastomotic leak in
      laparoscopic colorectal resection appear to be equivalent to traditional surgery,
      whereas the rate of perineal wound sepsis is lower. Comparative studies are
      needed to determine the differential costs of the septic episodes associated with
      the two approaches.

PMID- 11285970
TI  - Use of a fluorescent bile acid to enhance visualization of the biliary tract and
      bile leaks during laparoscopic surgery in rabbits.
AB  - BACKGROUND: We set out to determine whether intravenously administered
      cholylglycylaminofluorescein (CGF), a fluorescent bile acid, would enhance the
      visualization of the biliary tract and bile leaks in rabbits undergoing
      laparoscopic cholecystectomy (LC). METHODS: CGF was infused at doses of 1, 5, and
      10 mg/kg b.w. Biliary recovery was determined spectrophotometrically (six
      rabbits). For LC (seven rabbits), a blue (fluorescein) filter was attached to the
      light source, and a fluorescein-emission filter was attached to the charge
      coupled device (CCD) camera. The biliary tract and bile leak (made by incising
      the gallbladder) was observed under standard and fluorescent illumination.
      RESULTS: Apple-green fluorescence appeared in 2 min and persisted for 30-60 min,
      enhancing visualization of bile duct anatomy as well as the bile leak. Biliary
      recovery of CGF at 90 min was high (86-96% of the infused dose). CONCLUSION: In
      rabbits, CGF is secreted quantitatively in bile, induces biliary fluorescence,
      and enhances visualization of the bile ducts and bile leaks when viewed with
      appropriate filters.

PMID- 11285972
TI  - Laparoscopic adrenalectomy of large cystic pheochromocytoma.

PMID- 11285971
TI  - Percutaneous endoscopic gastrostomy after abdominal surgery.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has been established as a
      minimally invasive and safe procedure to provide nutritional support in patients
      unable to swallow food properly. However, a relative contraindication for the
      procedure is the existence of previous abdominal surgery. METHOD: We described
      our experience in performing PEG on 37 patients who had undergone surgery for
      upper abdominal diseases 10 days to 25 years previously. This group of 37
      patients, 22 of whom had been subjected to laparotomy in the previous 2 weeks,
      was compared with 291 patients who had an intact abdomen regarding failure of the
      procedure to be performed, major and minor complications, and mortality. RESULTS:
      The two groups were found to be comparable: failure rates of 2.71% (1/37) and
      1.72% (5/291), no major complications, no mortality, minor complication rates of
      2.77% (1/36) and 2.44% (7/286). CONCLUSIONS: The PEG procedure is associated with
      minimal risk even in patients previously subjected to upper abdominal surgery, as
      long as transillumination of the stomach and finger palpation are seen clearly
      during endoscopy.

PMID- 11285973
TI  - Radiologic gastrostomy.

PMID- 11285974
TI  - Transthoracic endoscopic sympathectomy.

PMID- 11285975
TI  - Laparoscopic incisional hernia repair.

PMID- 11285976
TI  - Exposure of human oocytes to endometrioma fluid does not alter fertilization or
      early embryo development.
AB  - BACKGROUND: Extensive endometriosis causes a mechanical disturbance in the pelvis
      leading to obstructive-type infertility. However, minimal or mild endometriosis
      is suspected to cause infertility, possibly through a humoral agent. Previous
      studies reported the presence of a factor in the serum of patients with
      endometriosis which reduced fertilization and early embryo formation in a rat IVF
      model. METHODS: In the present article, we report a comparison of oocytes exposed
      to endometrioma fluid and oocytes not exposed (controls) in the context of a
      human IVF setting. We have been in the practice of aspirating oocytes into
      prewarmed 60-ml syringes containing culture medium. We have shown previously that
      this technique reduces the length of oocyte retrieval without compromising
      success. In 14 women undergoing oocyte retrieval, we inadvertently entered an
      endometrioma. This resulted in retrieved oocytes that were either exposed or not
      exposed to endometrioma fluid. RESULTS: In contrast to previous reports, we found
      no difference in fertilization or early embryo development between the two
      groups. The fertilization rate for oocytes exposed to an endometrioma was 60%,
      versus 56% for controls. The good-quality embryo formation rate for oocytes
      exposed to an endometrioma was 45%, versus 46% for controls.

PMID- 11285977
TI  - The expression of pseudogene cyclin D2 mRNA in the human ovary may be a novel
      marker for decreased ovarian function associated with the aging process.
AB  - PURPOSE: Our purpose was to investigate the expression pattern of cyclin D2 and
      pseudogene cyclin D2 mRNA in the human ovary with age. METHODS: After extraction
      of the total RNA from ovarian tissues of 23 premenopausal patients, cyclin D2 and
      pseudogene cyclin D2 mRNAs were measured by the reverse transcription-polymerase
      chain reaction technique using cyclin D2 and pseudogene cyclin D2 specific
      primers. Analysis of the cyclin D2 and pseudogene cyclin D2 mRNA expression
      pattern with age and correlation analysis were carried out. RESULTS: A 489-bp
      cyclin D2 band and a 441-bp pseudogene cycin D2 mRNA band were detected in the
      human ovarian tissue. While cyclin D2 mRNA expression showed a decreasing
      tendency with age (P = 0.17), pseudogene cyclin D2 mRNA expression increased with
      age (P < 0.05). Pseudogene cyclin D2 mRNA expression showed a negative
      correlation with cyclin D2 mRNA (R = -0.35, P < 0.03). CONCLUSION: The expression
      of pseudogene cyclin D2 mRNA in the human ovary increases with age, which may be
      a novel marker for decreased ovarian function associated with the aging process.

PMID- 11285978
TI  - A rise of the serum level of von Willebrand factor occurs before clinical
      manifestation of the severe form of ovarian hyperstimulation syndrome.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) appears to be caused by
      increased capillary permeability in the vascular endothelial cells. Such cells
      secrete excess amounts of von Willebrand factor (vWF), a large adhesive
      glycoprotein. METHODS: We retrospectively evaluated the circulating levels of vWF
      and of vascular endothelial growth factor (VEGF) twice, on the days of oocyte
      retrieval and embryo transfer, in 46 women who developed early-onset OHSS.
      RESULTS: Nineteen, 14, and 13 women developed mild, moderate, and severe OHSS,
      respectively. Inconsistent changes were observed in the VEGF during oocyte
      retrieval and embryo transfer. However, the net increase in serum vWF during that
      period showed an increase in absolute value at the time of embryo transfer that
      paralleled an increase in the severity of OHSS. That is, in mild OHSS, the serum
      vWF increased from 140 +/- 44 to 164 +/- 28%; in moderate OHSS, it increased from
      113 +/- 47 to 186 +/- 22%; and in severe OHSS, it increased from 120 +/- 35 to
      274 +/- 63%. All 9 women with a vWF level > 230% at embryo transfer developed
      severe OHSS, while 9 of 13 women with severe OHSS exhibited a vWF > 230% at
      embryo transfer. CONCLUSION: The results suggest that a rise of the serum level
      of vWF occurs prior to clinical manifestation of OHSS in patients with severe
      OHSS but not in patients with mild OHSS.

PMID- 11285979
TI  - Ovarian hyperstimulation syndrome complicating a spontaneous singleton pregnancy:
      a case report.
AB  - It has been known that most cases of ovarian hyperstimulation syndrome (OHSS) are
      associated with the use of exogenous gonadotropins to induce multiple ovulation.
      However, OHSS is infrequently associated with a spontaneous ovulatory cycle,
      usually in the case of multiple gestations, hypothyroidism, or polycystic ovarian
      syndrome. We report a case of severe OHSS in a spontaneously pregnant woman with
      no underlying disease.

PMID- 11285980
TI  - Reflections on the cost-effectiveness of recombinant FSH in assisted
      reproduction. The clinician's perspective.
AB  - PURPOSE: To analyze the relative cost-effectiveness of recombinant FSH (rFSH) and
      urinary FSH (uFSH) in assisted reproduction techniques (ART). METHODS:
      Calculation of the average cost-effectiveness ratio and the incremental cost
      effectiveness ratio to compare costs and effects (pregnancy rates) of the two
      therapeutic options (rFSH and uFSH). RESULTS: Assuming that the cost of the
      procedure per ART cycle is between 100,000 pesetas (601 euro) and 150,000 pesetas
      (901.52 euro), and pricing the GnRH analogues used for pituitary suppression at
      35,000 pesetas (210.3 euro), the cost-effectiveness ratio is better for rFSH than
      for uFSH, implying that the cost per pregnancy is lower when the recombinant
      preparation is used. CONCLUSIONS: In ART, the use of rFSH is more cost-effective
      than uFSH.

PMID- 11285981
TI  - Distributive justice in the allocation of donor oocytes.
AB  - Due to the shortage of oocyte donors, the waiting lists are lengthening. This
      raises the ethical question of how the available oocytes should be distributed
      among candidate recipients. The paper clarifies the ethical structure of the
      allocation process to find a set of rules that generates decisions that are
      acceptable for all people involved. The selection includes two steps: admission
      to the waiting list and ranking of those on the list. The following criteria can
      be used to decide about the admission of candidates: success rate, health risks,
      age, parental competence, nationality, primary versus secondary infertility, and
      capacity to pay. Four criteria may function to rank recipients who should have
      first priority for receiving oocytes: waiting time, medical urgency, phenotypic
      matching, and synchronization. The introduction of a point system is defended
      because it allows balancing of the different ethical principles involved and
      because it installs an objective system of operating rules which avoid favoritism
      and personal biases.

PMID- 11285982
TI  - Tenth anniversary of preimplantation genetic diagnosis.

PMID- 11285983
TI  - Assessing outcome.

PMID- 11285984
TI  - IVF births and pregnancies: an exploration of two methods of assessment using
      life-table analysis.
AB  - PURPOSE: Our purpose was to explore two methods of expressing the performance of
      IVF programs. METHODS: Using life-table methods, hazard and cure rates and a
      "monthly fecundability rate" were calculated for an Ontario IVF clinic. The rates
      were evaluated for their meaningfulness as indicators of the clinic's
      performance. RESULTS AND CONCLUSIONS: While the hazard rate describes monthly
      fertility among those who will eventually become pregnant, the fecundability rate
      describes fertility for all patients who enter the program, making it the more
      appropriate index for program comparisons. However, from a prospective patient's
      perspective, both methods are valid indices for summarizing a program's
      performance.

PMID- 11285985
TI  - Development of blastocyst-stage embryos after round spermatid injection in
      patients with complete spermiogenesis failure.
AB  - PURPOSE: Our purpose was to evaluate the progression of embryos derived from
      round spermatid injection to the blastocyst stage and compare the results with
      those obtained by the use of testicular or epididymal spermatozoa. METHODS:
      Thirty-eight patients with azoospermia enrolled in this study. In 29 patients
      with obstructive or nonobstructive azoospermia, spermatozoa were recovered from
      epididymis or testis. In the remaining nine cases with nonobstructive
      azoospermia, only round spermatids were found in seven, whereas in two of the
      patients, there were no elongated or round spermatids. Six of these cases
      underwent round spermatid injection. RESULTS: Twenty-one of 29 patients with
      injection of spermatozoa underwent embryo transfer on day 3, and 10 pregnancies
      (47.6%) were obtained. In eight cycles, embryos were further cultured for delayed
      transfer. In six cases undergoing round spermatid injection, no transfer was
      performed on day 3 and extended culture with delayed embryo transfer was applied.
      The mean number of fertilized oocytes and mean number of embryos on day 3 and
      also the fertilization rate and mean number of good-quality embryos on day 3,
      mainly grade 1 or 2, were statistically significantly higher in the spermatozoa
      group than the round spermatid injection group. Compared to the spermatozoa
      group, the number of arrested embryos was significantly higher and the number of
      blastocyst-stage embryos and number of good-quality blastocysts were
      significantly lower in the spermatid injection group. No blastocysts developed in
      two spermatid cycles and embryo transfer was not possible, and in the remaining
      four cycles, after at least one blastocyst transfer, no pregnancies were
      achieved. However, in eight cycles with extended culture in the spermatozoa
      group, embryo transfers were achieved in all and three pregnancies, for a
      pregnancy rate of 37.5%, were obtained after blastocyst transfer. CONCLUSIONS:
      Our preliminary results showed that round spermatid injection was associated with
      a significantly lower fertilization and embryo development rate and a
      significantly higher developmental arrest rate compared with the injection of
      spermatozoa. Extended culture and delayed embryo transfer did not improve the
      clinical outcome after round spermatid injection, and these results suggested a
      developmental failure in embryos preventing successful implantation after round
      spermatid injection.

PMID- 11285986
TI  - Human chorionic gonadotropin-to-oocyte collection interval in a superovulation
      IVF program. A prospective study.
AB  - PURPOSE: The aim of this study was to investigate whether the hCG-oocyte
      collection interval has any influence on the oocyte recovery rate, fertilization
      rate, and outcome of IVF-ET cycles. METHODS: Five hundred thirty-three
      consecutive patients undergoing their first IVF-ET treatment cycle at King's
      Assisted Conception Unit between 1993 and 1995 were included in this study.
      RESULTS: There was no significant difference in the oocyte recovery rates,
      fertilization rates, or outcome of IVF-ET treatment among the hCG-oocyte
      collection intervals examined (33-41 hr). None of the 533 women studied had
      ovulated before oocyte collection. CONCLUSIONS: The results do not suggest a
      trend toward increased ovulation more than 36 hr after hCG administration.

PMID- 11285987
TI  - Determination of the efficiency of controlled ovarian hyperstimulation in the
      gonadotropin-releasing hormone agonist-suppression cycle using the initial
      follicle count during gonadotropin stimulation.
AB  - PURPOSE: Our purpose was to evaluate the relationship between the initial
      follicle count during gonadotropin stimulation after gonadotropin-releasing
      hormone (GnRH) agonist suppression and the efficiency of controlled ovarian
      hyperstimulation (COH) in patients receiving treatment with assisted reproductive
      technologies (ARTs). METHODS: A total of 338 COH procedures in 291 couples was
      performed with cycles that reached the stage of oocyte retrieval. The ovarian
      antral follicle number was measured using transvaginal ultrasonography at the
      folliculometry during gonadotropin stimulation by GnRH agonist suppression in
      patients undergoing ARTs. Controlled ovarian hyperstimulation was accomplished
      using GnRH agonist down-regulation combined with FSH and menotropin stimulation.
      The characteristics of oocytes after retrieval and embryos after in vitro culture
      and the pregnancy rates were assessed. RESULTS: The procedures performed included
      195 ET cycles, 129 TET cycles, and 14 incomplete cycles. The treatment cycles
      were divided into four categories according to the antral follicle number (i.e.,
      < or = 5, 6-10, 11-15, and > or = 16) at the first folliculometry to evaluate the
      influence of various factors. The antral follicle count correlated significantly
      with the patient age, dosage of gonadotropins, serum estradiol concentration,
      number of antral follicles (> or = 13 mm) while receiving hCG injections, number
      of oocytes retrieved, and, later, number of embryos transferred. There was a
      trend toward an increasing number of pregnancies per cycle as the number of
      antral follicles increased (14.7, 26.5, 44, and 45%, respectively). CONCLUSIONS:
      We were able to predict the efficiency of COH and outcome of ARTs based on the
      follicle count during the first folliculometry during gonadotropin stimulation
      after GnRH agonist suppression. The results of the folliculometry significantly
      predicted the ovarian response to COH and the outcome of ARTs in the current
      treatment cycle.

PMID- 11285989
TI  - Epidemiology of osteoporosis.
AB  - This review has shown that osteoporosis is a major public health problem because
      of its association with fracture. It is now possible to predict future risk of
      fracture by measuring BMD with noninvasive techniques. The relation between BMD
      and fracture is comparable to that between blood pressure and stroke such that
      fracture risk can be assessed from a definition of osteoporosis using bone mass
      and past history of fracture. Because some of the risk factors for peak bone
      mass, involutional bone loss, and fracture are now characterized, coupled with
      innovative agents capable of retarding bone loss, it is becoming possible to
      generate preventive strategies, for the entire population as well as for those at
      highest risk.

PMID- 11285988
TI  - Development of a well-defined medium for the in vitro maturation of immature
      bovine cumulus-oocyte complexes.
AB  - PURPOSE: Our purpose was to develop a well-defined medium for the in vitro
      maturation (IVM) of immature bovine cumulus-oocyte complexes (COC). METHODS: The
      COC were cultured in the presence of three protein supplementations: fetal bovine
      serum (FBS), bovine serum albumin, and Synthetic Serum Substitute. The embryos
      obtained after in vitro fertilization of IVM oocytes were cocultured with Vero
      cells and their development to the morula and blastocyst stages was studied.
      RESULTS: When FBS was absent from the IVM medium, a significantly lower
      fertilization rate was observed, followed by a decrease in the percentage of
      embryos reaching the blastocyst stage. When FBS was replaced by a defined protein
      supplementation, the best results were obtained with Synthetic Serum Substitute.
      CONCLUSIONS: Adequate protein supplementation of the IVM medium optimizes the
      fertilization rate and the development of bovine IVM oocytes. The implication of
      these results in the human field is discussed.

PMID- 11285990
TI  - Calcium and vitamin D in osteoporosis.
AB  - Calcium and vitamin D are useful adjunctive therapies in the prevention and
      treatment of osteoporosis. Peak BMD is optimally achieved with sustained optimal
      calcium and vitamin D intakes. Calcium and vitamin D intakes continue to be
      important after the third decade and into senescence. Although calcium and
      vitamin D are not therapies to be used alone to prevent early postmenopausal bone
      loss, they assume more prominent roles in late menopause and in the elderly to
      preserve bone health with advancing age. Calcium and vitamin D supplementation is
      an important adjunctive therapy to use together with antiresorptive therapies.

PMID- 11285991
TI  - Role of exercise in preventing and treating osteoporosis.
AB  - Bone mass at any time of life reflects the totality of events that have impinged
      on the skeleton to that point. For adults, these events include those that have
      influenced the acquisition of bone during years of growth, resulting in the
      achievement of skeletal maturity, or "peak bone mass," as well as those that have
      subsequently influenced bone losses. For each limb of this trajectory, physical
      activity has been implicated as a powerful and independent factor. This article
      reviews current evidence regarding the relation of habitual physical activity to
      bone acquisition and maintenance, the skeletal consequences of exercise training,
      and the clinical value of exercise for patients with skeletal frailty.

PMID- 11285992
TI  - Role of estrogens in the management of postmenopausal bone loss.
AB  - It is well known that estrogen deficiency is the major determinant of bone loss
      in postmenopausal women. Estrogen is important to the bone remodeling process
      through direct and indirect actions on bone cells. The largest clinical
      experience exists with estrogen therapy, demonstrating its successful prevention
      of osteoporosis as well as its positive influence on oral bone health, vasomotor
      and urogenital symptoms, and cardiovascular risk factors, which may not occur
      with other nonestrogen-based treatments. Compliance with HRT, however, is
      typically poor because of the potential side effects and possible increased risk
      of breast or endometrial cancer. Nevertheless, there is now evidence that lower
      doses of estrogens in elderly women may prevent bone loss while minimizing the
      side effects seen with higher doses of estrogen. Additionally, when adequate
      calcium, vitamin D, and exercise are used in combination with estrogen-based
      treatments, more positive increases occur in bone density. The benefits and risks
      of HRT must be assessed on a case-by-case basis, and the decision to use HRT is a
      matter for each patient in consultation with her physician. Estrogen-based
      therapy remains the treatment of choice for the prevention of osteoporosis in
      most postmenopausal women, and there may be a role for estrogen to play in the
      prevention of corticosteroid osteoporosis. Combination therapies using estrogen
      should probably be reserved for patients who continue to fracture on single
      therapy or should be used in patients who present initially with severe
      osteoporosis.

PMID- 11285993
TI  - The role of selective estrogen receptor modulators in the prevention and
      treatment of osteoporosis.
AB  - Osteoporosis can affect almost everyone in the population, and although clinical
      outcome of fracture is manifested in late life, the disease process begins in the
      early postmenopausal years in women. The pharmacologic agents currently available
      for osteoporosis prevention and treatment act by inhibiting bone resorption, and
      include estrogen or hormone replacement therapy (estrogen with progestin),
      bisphosphonates, salmon calcitonin nasal spray, and selective estrogen receptor
      modulators (SERMs). Raloxifene is a benzothiophene SERM that has estrogen against
      effects in bone and on serum lipid metabolism and estrogen antagonist effects on
      breast and uterine tissue. This article summarizes the effects of these
      antiresorptive agents, as measured by changes in bone mineral density,
      biochemical markers of bone turnover, and incident fractures in postmenopausal
      osteoporosis.

PMID- 11285994
TI  - Calcitonin.
AB  - Calcitonin reduces the risk of vertebral fracture in postmenopausal women with
      osteoporosis. Calcitonin produces small increments in the bone mass of the spine
      and modestly reduces bone turnover in women with osteoporosis. No significant
      effect on nonvertebral fractures has been observed. Calcitonin may have analgesic
      benefit.

PMID- 11285995
TI  - Osteoporosis in men.
AB  - Although less common than in women, osteoporosis in men is a prevalent worldwide
      problem with important socioeconomic implications. Our understanding of this
      condition in men is growing, but there remains a great deal more to be
      determined. Definitions for osteoporosis in men are needed. Cost-effective
      guidelines on who should be investigated and treated, and how, are clearly
      necessary. The role of bone mineral densitometry in diagnosis and treatment
      decisions needs to be clarified. The efficacy of drug therapies for osteoporosis
      in men requires greater attention. Currently, a large multicenter study is
      underway in the United States and should provide much needed insight into the
      epidemiology of osteoporosis in men.

PMID- 11285996
TI  - Treatment of osteoporosis with bisphosphonates.
AB  - Bisphosphonates are safe and effective agents for treatment and prevention of
      osteoporosis. Alendronate and risedronate are the best studied of all agents for
      osteoporosis in terms of efficacy and safety. They increase bone mass. In
      patients who have established osteoporosis, they reduce the risk of vertebral
      fractures. They are the only agents shown in prospective trials to reduce the
      risk of hip fractures and other nonvertebral fractures. They are approved by the
      US FDA for prevention of bone loss in recently menopausal women, for treatment of
      postmenopausal osteoporosis, and for management of glucocorticoid-induced bone
      loss. Other bisphosphonates (e.g., etidronate for oral use, pamidronate for
      intravenous infusion) are also available and can be used off-label for patients
      who cannot tolerate approved agents. Bisphosphonates combined with estrogen
      produce greater gains in bone mass compared with either agent used alone; whether
      there is a greater benefit of combination therapy on fracture risk is not clear.
      Combining a bisphosphonate with raloxifene or calcitonin is probably safe,
      although data on effectiveness are lacking.

PMID- 11285997
TI  - Emerging anabolic treatments for osteoporosis.
AB  - Therapy for osteoporosis is principally centered on the use of agents that block
      bone resorption and supplementation with vitamin D and calcium. Although these
      drugs are effective in reducing the risk of subsequent fractures, and modestly
      increasing bone density, most patients being treated for osteoporosis still have
      low bone mass and a greater risk of fracture. Anabolic agents stimulate bone
      formation, strength, and mass. In addition, there is emerging evidence that
      anabolic agents can reduce subsequent fracture risk. The two most promising
      agents, parathyroid hormone (PTH) and GH/IGF-I, act to increase osteoblast
      mediated bone formation. A review of the potential usefulness of PTH and GH/IGF-I
      is presented.

PMID- 11285998
TI  - An update on glucocorticoid-induced osteoporosis.
AB  - In general, bone loss from glucocorticoid treatment occurs rapidly within the
      first 6 months of therapy. Glucocorticoids alter bone metabolism by multiple
      pathways; however, the bone loss is greatest in areas rich in trabecular bone.
      Preventive measures should be initiated early. It is the author's opinion that
      all subjects initiating treatment with prednisone at 7.5 mg or greater require
      calcium supplementation (diet plus supplement) at a dose of 1500 mg and vitamin D
      at a dose of 400 to 800 IU/d. If the patient is going to remain on this dose of
      glucocorticoid for more than 4 weeks, an antiresorptive agent should be started
      (e.g., estrogen, bisphosphonate, raloxifene). If a patient has established
      osteoporosis and is either initiating glucocorticoid therapy or is chronically
      treated with prednisone at 5 mg d or greater in addition to calcium and vitamin D
      supplementation, a potent antiresorptive agent (bisphosphonate) should be
      started. A bone mineral density measurement of either the lumbar spine or the hip
      may be helpful is assessing an individual's risk of osteoporosis, may improve
      compliance with treatment, and can be used to monitor the efficacy of the
      prescribed therapy. There is no reason to withhold treatment for glucocorticoid
      induced bone loss until a bone mass measurement is taken, however. In motivated
      patients, a weight-bearing and resistance exercise program should be prescribed
      to help retain muscle strength and prevent depression. If hypercalciuria develops
      with glucocorticoid use, either thiazide diuretics or sodium restriction may be
      helpful. In patients who continue to lose bone or experience fracture's despite
      antiresorptive therapy while on glucocorticoids, bone-building anabolic agents
      (e.g., hPTH 1-34 or PTH 1-84) may be available someday soon.

PMID- 11285999
TI  - The nonskeletal consequences of osteoporotic fractures. Psychologic and social
      outcomes.
AB  - The prevalence of osteoporosis is rising as the population of the United States
      and other developed countries ages. These increasing numbers of people have
      motivated pharmaceutical companies to develop and market several antiresorptive
      medications that can slow down the bone loss associated with osteoporosis.
      Although these are not cures for this disease, they are an important first step
      in a vital ongoing public health effort to prevent osteoporosis in the future and
      to manage osteoporosis now. We cannot expect to remediate the problems caused by
      this disease if we attend only to its skeletal implications. Like any other
      chronic disease, osteoporosis has significant psychologic and social
      consequences. From anxiety and depression to social withdrawal and isolation, if
      these problems are left unresolved, they can have a significant negative impact
      not only on health issues but also on overall quality of life. No quick fixes
      exist for the numerous ways in which osteoporosis can transform an autonomous
      person into a dependent and hopeless patient. In part, responsibility for helping
      this patient rests with the medical community. Referrals to appropriate providers
      can improve a patient's physical and emotional well-being. Physician specialists
      can help the patient manage comorbid conditions. Physical and occupational
      therapists can teach exercises, home safety, and safe movement. Social workers
      can provide a framework for coping that enables individuals to improve their
      interpersonal interactions and minimize stress in their lives. Nutritionists,
      pharmacists, nurses, and other health care professionals can make major
      contributions to the quality of life of people with osteoporosis and should be
      encouraged to do so. Unfortunately, managed care has set policies that deprive
      patients with osteoporosis of the kinds of care that would be most useful to
      them. As we have advocated for the last 15 years, a multidisciplinary approach
      offers patients the most positive overall way to manage osteoporosis. Therefore,
      new alternatives need to be examined, alternatives that provide both low-cost and
      high-quality care. In the long run, patients who practice self-management, that
      is, those who take responsibility for their own calcium and vitamin D intake, are
      compliant with medications, exercise, and practice home safety, and who have a
      healthy outlook, can control their osteoporosis. The most effective intervention
      for the future may be to teach individuals how to use self-management strategies
      so that they can take charge of their osteoporosis and positively influence their
      quality of life.

PMID- 11286000
TI  - Biochemical markers to survey bone turnover.
AB  - Molecular markers of bone turnover have gained increasing relevance in the
      evaluation of patients with metabolic bone diseases. Their clinical applications
      include the assessment of future osteoporotic fracture risk, complementation of
      bone density measurements, diagnosis of certain metabolic osteopathies,
      therapeutic decision making, and monitoring of therapeutic efficacy and patient
      compliance. One should be aware, however, that the results from large
      epidemiologic or clinical trials are sometimes difficult to translate into the
      everyday clinical situation. The individual patient often has more than one
      disease that might affect either bone turnover or the handling of the parameters
      mentioned (or both). Analytic and biologic variability of bone markers can be
      significant and also needs to be considered when using these indices. In the
      scientific setting, conventional and new markers of bone turnover can help to
      elucidate formerly unknown mechanisms and pathways. Because the development of
      ever more specific and sensitive markers of bone metabolism is progressing
      rapidly, we are likely to witness new insights into the pathophysiology of bone
      diseases in the near future.

PMID- 11286001
TI  - Update on bone density measurement.
AB  - Bone densitometry is a clinically accepted technique for assessing fracture risk
      and evaluating skeletal change. The proper clinical use of densitometry requires
      an understanding of the available techniques, their appropriate application, and
      the potential sources of measurement error. Recent clinical guidelines recommend
      that all women over the age of 65 years and all postmenopausal women with risk
      factors should have their bone density assessed. With the advent of smaller
      portable devices, bone density measurements are now widely available. In
      particular, ultrasound techniques, which do not use radiation, have particular
      promise for widespread screening applications. Peripheral densitometry alone
      cannot adequately address all clinical questions, particularly the question of
      monitoring subtle changes in bone density. For this purpose, central
      densitometers are still preferred. For any bone density measurement to be
      clinically useful, it must be performed with careful attention to detail,
      particularly with regard to instrument calibration, patient positioning,
      measurement analysis, and interpretation.

PMID- 11286002
TI  - Sadomasochistically oriented behavior: diversity in practice and meaning.
AB  - One hundred and eighty-four subjects (22 women and 162 men) who were members of
      two sadomasochistically oriented clubs answered a semistructured questionnaire
      containing items relating to a variety of sexual behaviors. Using a multivariate
      statistical analysis that geometrically represents the co-occurrence of
      individual actions as a visual array (Guttman (1954). In Lazarfeld, P. E. (ed.),
      Mathematical Thinking in the Social Sciences, Free Press, Glencoe, IL.) four
      qualitatively different sexual scripts emerged: hypermasculinity; administration
      and receiving of pain; physical restriction; and psychological humiliation.
      Although similar themes have been suggested before, this study demonstrated their
      empirical base. Humiliation was significantly associated more with females and
      with heterosexual orientation in men, while hypermasculinity was associated with
      males and with homosexual orientation in men.

PMID- 11286003
TI  - Sexual attitudes and number of partners in young British men.
AB  - The relationship between sexual attitudes and number of heterosexual partners in
      a survey-based and nationally representative random sample of 551 British men
      aged 16-25 years was examined. The main predictor of the number of partners in
      the last 5 years was the time since the first sexual intercourse, whereas age,
      marital status, education, social class, smoking, and alcohol consumption
      contributed on a smaller but significant level. Sexual attitudes were summarized
      in terms of three underlying dimensions which could be described as
      permissiveness, attitudes toward sexual relations of same-sex partners, and
      importance of orgasm for sex. None of these was a significant predictor of the
      number of partners in the last 5 years. Both permissiveness and number of
      partners were associated with the age of first sexual intercourse and other
      background variables indicating opportunities for social contact. In conclusion,
      common factors of sexual attitudes and the number of sexual partners are not
      directly related but rather jointly predicted by a very similar set of background
      variables such as age, time since first sexual intercourse, social class,
      smoking, and alcohol consumption. Given the absence of a significant relationship
      between sexual attitudes and number of young men's partners, promoting safer sex
      may be a more sensible strategy than trying to change these attitudes.

PMID- 11286004
TI  - Personality, individual differences, and preferences for the sexual media.
AB  - The extent to which personality and individual differences predict preferences
      for and choices of various forms of sexual media was examined. Personality (e.g.,
      intelligence, aggression) and individual difference factors (e.g., prior sexual
      experience) were assessed in 160 undergraduate men. These men also indicated
      their preferences for and choices of various forms of sexual media (e.g.,
      "erotic," female insatiability, violent). As expected, individual differences
      were predictive, with, for example, men lower in intelligence and higher in
      aggressive/antisocial tendencies having a higher preference for violent sexual
      stimuli than men higher in intelligence and lower in aggressive/antisocial
      tendencies had. In addition, as much as 50% of the variation in the preference
      for violent sexual materials was accounted for by an additive combination of
      individual differences and self-report arousal to these materials. Finally, the
      results indicated that, when given a choice to view different media materials,
      the men chose a broad range of media materials, although the "female
      insatiability" films were more popular than the other sexual films (e.g.,
      "erotic" or violent). Results are discussed in relation to recent research and
      psychological theories that view adults as active in choosing their own social
      environments.

PMID- 11286005
TI  - Sexual functioning after treatment for testicular cancer--review and meta
      analysis of 36 empirical studies between 1975-2000.
AB  - Literature concerning sexual functioning after treatment for testicular cancer
      from 1975-2000 is reviewed. After a literature search in Medline and Psylit was
      conducted, as well as a search for cross-references made, a meta-analysis was
      performed. To describe sexual functioning, several aspects of the sexual response
      cycle were used: sexual desire, sexual arousal, erection, and orgasm; ejaculatory
      function, sexual activity, and sexual satisfaction were used as well. The number
      of patients included in the studies as well as treatment modalities were taken
      into account. A total of 36 relevant studies was screened (28 retrospective and 7
      prospective studies), concerning 2,786 cases of testicular cancer. Meta-analysis
      revealed that ejaculatory dysfunction was reported most frequently and was
      related to surgery in the retroperitoneal area. Erectile dysfunction was related
      to irradiation, but was reported least frequently. Other sexual functions were
      not related to treatment modality. Meta-analysis revealed no deterioration of
      sexual functioning in the course of time, except a decrease in sexual desire and
      an increase in sexual satisfaction. Retrospective studies reported more sexual
      dysfunction than did prospective studies. Detailed analysis of separate studies,
      however, revealed a wide variation in reported sexual morbidity, as well as in
      assessment methods. Somatic consequences of disease and treatment may reduce
      ejaculation; however, other aspects of sexual functioning are not clearly related
      to disease- or treatment-related factors and may instead refer to a psychological
      vulnerability caused by one's confrontation with a life-threatening, genito
      urinary disease, such as testicular cancer.

PMID- 11286006
TI  - Kallmann's syndrome and transsexualism.
AB  - Until the present, in the world literature only one patient with Kallmann's
      syndrome has been reported who became transsexual. This patient was seen almost
      50 years ago. In this report, a second case is presented to encourage studies of
      the sexual and gender identity development in these patients. This patient's rare
      endocrine disorder and secondary emotional problems have led to negative
      consequences because appropriate treatment of her transsexualism became
      impossible.

PMID- 11286007
TI  - The use of essential drugs.
AB  - This report presents the recommendations of a WHO Expert Committee responsible
      for updating and revising the Model List of Essential Drugs. The first part
      describes the criteria for the selection of essential drugs and pharmaceutical
      dosage forms, and includes discussion of quality assurance, pharmacovigilance,
      drug utilization studies, drug information and educational activities, and future
      developments of the model list. In the light of increasing resistance to
      antimicrobials, particular attention is drawn to the need for and use of reserve
      antimicrobials. The second part presents the eleventh revised model list,
      together with details of the changes that have been made, a glossary of terms and
      an alphabetical index of all the drugs included.

PMID- 11286008
TI  - Evaluation of certain food additives and contaminants.
AB  - This report represents the conclusions of a Joint FAO/WHO Expert Committee
      convened to evaluate the safety of various food additives and contaminants, with
      a view to recommending Acceptable Daily Intakes (ADIs) for humans, and to prepare
      specifications for the identity and purity of food additives. The first part of
      the report contains a general discussion of the principles governing the
      toxicological evaluation of food additives and contaminants (including flavouring
      agents), assessments of the intake of contaminants, and the establishment and
      revision of specifications. A summary follows of the Committee's evaluations of
      toxicological data on various specific food additives (hydrogenated poly-1
      decene, erythritol, curdlan, gamma-cyclodextrin and sodium sulfate), substances
      used in food fortification (sodium iron EDTA), flavouring agents, peanut oil,
      soya bean oil and contaminants (lead, methylmercury and zearalenone). Annexed to
      the report are tables summarizing the Committee's recommendations for ADIs of the
      food additives and substance used in food fortification considered, changes in
      the status of specifications for these substances and specific flavouring agents,
      further information required and the report of an ad hoc Panel on Food Allergens.

PMID- 11286009
TI  - The contribution of mesangial cell proliferation to progressive glomerular
      injury.
AB  - Mesangial cell proliferation is a general characteristic of a variety of
      glomerular diseases. Therefore, an understanding of the regulatory mechanism is
      important for treatment of glomerular diseases. The present review shows that the
      growth arrest gene 6 (Gas 6) is a new autocrine growth factor of mesangial cells
      and that warfarin inhibits mesangial cell proliferation by inhibiting the gamma
      carboxylation of Gas 6 in vitro and in vivo. The present findings also show that
      a vitamin D analog (22-oxa-calcitriol) is a new growth regulator of mesangial
      cells in vitro and in vivo. These findings indicate that these compounds have
      considerable potential for therapeutic use in the treatment of progressive
      glomerular disease.

PMID- 11286010
TI  - DNA adduct formation by 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in rat
      colon.
AB  - A food-born carcinogen, 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) induces
      cancer in the rat colon. The mechanism for colonic DNA adduct formation leading
      to cancer by IQ was studied using a colostomized F344 rat model. In this model,
      the transverse colon of the rat was colostomized, which produced a fecal stream
      positive proximal colon and a negative distal colon were produced. When IQ (50
      mg/kg) was administered into the distal colon of the colostomized rats (n = 5),
      the ratio of the DNA adduct level of the distal colonic mucosa to the paired
      muscular layer 24 hr after dosage was 2.02, whereas that was 1.51 and 1.37 when
      IQ was administered into the stomach (n = 6) and the vein (n = 5), respectively.
      This suggested that luminal exposure of IQ induced DNA adduct formation. Since IQ
      (an amine form) has no reactivity toward DNA, these findings suggested that IQ
      was immediately activated in the absorbed mucosal cells and reacted with DNA.
      However, most of the IQ absorbed was metabolically activated in the liver,
      distributed by blood circulation, and formed DNA adducts in the colonic mucosa
      and muscular layer.

PMID- 11286011
TI  - CD40 and IFN-gamma dependent T cell activation by human bronchial epithelial
      cells.
AB  - We examined whether freshly isolated human bronchial cells (HBEC) and bronchial
      epithelial cell line/BEAS-2B cells expressed surface molecules required for APC
      function. These cells expressed CD40 and ICAM-1, but not B7-1, B7-2 or HLA-DR
      molecules. Treatment of these cells with IFN-gamma resulted in enhanced
      expression of CD40 and ICAM-1 as well as induction of HLA-DR expression. Th2
      cytokines such as IL-4 and IL-5, proinflammatory cytokine of GM-CSF and
      nonspecific activator endotoxin had no effect on these phenotypic expressions.
      Functional examinations showed that allogeneic lymphocytes purified from
      peripheral blood strongly proliferated in response to BEAS-2B cells cultured with
      IFN-gamma, but only weakly compared with those without IFN-gamma. When allogeneic
      lymphocytes were purified to CD4+ cells, the proliferative response against BEAS
      2B cells was abolished. Blockade of CD40-CD40L interaction by anti-CD40 antibody
      also inhibited the proliferation of lymphocytes to BEAS-2B cells, although this
      treatment showed a minimum effect on the response to allogeneic MNC. Thus,
      bronchial epithelial cells have the ability to present allogeneic antigens to T
      cells in both CD40- and IFN-gamma-dependent manners under the presence of third
      party cells that transduce co-stimulatory signals.

PMID- 11286012
TI  - Signal transduction of reactive oxygen species and mitogen-activated protein
      kinases in cardiovascular disease.
AB  - Reactive oxygen species (ROS), generated by reduction-oxidation (redox)
      reactions, have been recognized as important chemical mediators that regulate
      signal transduction. It has been reported that increase in ROS generation may
      relate to a risk for cardiovascular diseases such as atherosclerosis, angina
      pectoris, and myocardial infarction. Therefore, understanding the ROS-generating
      biological processes and ROS-induced intracellular signaling will be informative
      to gain insights into the pathogenesis of these diseases. In this review, we
      focus on the sources and reactions of ROS in the cardiovascular system and the
      role of mitogen-activated protein (MAP) kinase pathway in redox-mediated signal
      transduction. Clinical implications of ROS and MAP kinase are then described to
      provide insight into the pathogenesis of various redox-sensitive cardiovascular
      diseases. The pathways responsible for ROS generation in the cardiovascular
      system may provide novel therapeutic targets.

PMID- 11286013
TI  - Asymptomatic case of congenital absence of the gallbladder.
AB  - Congenital absence of the gallbladder is rare among biliary abnormalities, and
      its preoperative diagnosis has been considered very difficult. We encountered a
      patient with congenital absence of the gallbladder and suggest a possible
      preoperative diagnosis of the abnormality, as well as reviewing the literature.

PMID- 11286014
TI  - Genetic modulation of immature T lymphocytes and its application.
AB  - T lymphocytes are the cells that play an essential role in regulating immune
      responses. The thymus is the organ in which T lymphocytes are generated. Our
      laboratory has investigated molecular signals that determine cell fate during T
      lymphocyte development in the thymus. To this goal, we have devised a technique
      in which one may efficiently introduce foreign genes into immature T lymphocytes.
      The somatic gene-transfer into developing T lymphocytes are likely useful to
      restore various immunodeficiencies and to establish immune tolerance to any
      introduced genes. The genetically engineered immune tolerance may be applied to
      reduce allergies and autoimmune diseases, as well as to sustain gene therapies by
      allowing prolonged survival of therapeutic vectors.

PMID- 11286015
TI  - Matrix metalloproteinases and bladder cancer.
AB  - Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes which
      degrade the extracellular matrix or components of the basement membrane. They
      have essential roles in tumor invasion and metastasis. In bladder cancer,
      elevated MMP-2 and MMP-9 expression in tumor tissues, correlated with tumor
      stage, grade or prognosis, were reported in several studies. Moreover, high
      levels of serum or urine MMP and TIMP were observed in patients with bladder
      cancer especially in advanced cases. However, the true roles of MMPs and TIMPs in
      bladder cancer progression are not yet clarified. Here, we discuss the roles and
      clinical implications of MMPs in bladder cancer.

PMID- 11286016
TI  - Neural mechanisms of motion sickness.
AB  - Three kinds of neurotransmitters: histamine, acetylcholine and noradrenaline,
      play important roles in the neural processes of motion sickness, because
      antihistamines, scopolamine and amphetamine are effective in preventing motion
      sickness. Histamine H1-receptors are involved in the development of the symptoms
      and signs of motion sickness, including emesis. On provocative motion stimuli, a
      neural mismatch signal activates the histaminergic neuron system in the
      hypothalamus, and the histaminergic descending impulse stimulates H1-receptors in
      the emetic center of the brainstem. The histaminergic input to the emetic center
      through H1-receptors is independent of dopamine D2-receptors in the chemoreceptor
      trigger zone in the area postrema and serotonin 5HT3-receptors in the visceral
      afferent, which are also involved in the emetic reflex. Antihistamines block
      emetic H1-receptors to prevent motion sickness. Scopolamine prevents motion
      sickness by modifying the neural store to reduce the neural mismatch signal and
      by facilitating the adaptation/habituation processes. The noradrenergic neuron
      system in the locus coeruleus is suppressed by the neural mismatch signal.
      Amphetamine antagonizes mismatch-induced suppression of noradrenergic neural
      transmission, resulting in preventing motion sickness.

PMID- 11286017
TI  - Expression of tyrosine hydroxylase in cerebellar Purkinje cells of ataxic mutant
      mice: its relation to the onset and/or development of ataxia.
AB  - This report describes recent studies on tyrosine hydroxylase (TH) expression in
      Purkinje cells of the cerebellum of ataxic mutant mice. An increased expression
      of TH in some Purkinje cells has been observed in two allelic groups of mutant
      mice, tottering and dilute. TH-positive Purkinje cells appeared preceding the
      onset of ataxia. Northern blot analysis revealed 2.1 kb of TH mRNA in the mutant
      cerebella, and the size was identical to that of TH transcripts in other brain
      regions. However, TH in Purkinje cells did not seem to participate in
      catecholamine biosynthesis. In vitro studies showed that cultured non
      catecholaminergic neurons expressed the TH transcripts following Ca2+ influx.
      Therefore, abnormal TH expression in the mutant Purkinje cells may indicate
      neuronal dysfunction caused by misregulation of intracellular Ca2+
      concentrations.

PMID- 11286018
TI  - PCR-dot blot hybridization based on the neuraminidase-encoding gene is useful for
      detection of Bacteroides fragilis.
AB  - Bacteroides fragilis is a Gram-negative obligate anaerobe frequently isolated
      from clinical specimens and sometimes causes severe septicemia in compromised
      hosts. Increasing interest has been shown in the enterotoxigenicity and drug
      resistance of B. fragilis in the field of medical microbiology. We previously
      reported rapid detection of this anaerobe by nested PCR targeting a neuraminidase
      encoding gene nanH. In the present study, we synthesized a digoxigenin-labeled
      oligonucleotide probe, NH1, which is specific for nanH of B. fragilis, and we
      combined the hybridization assay using NH1 with the nanH-PCR to detect this
      anaerobe in a bacteremia model mice. In the specificity test, the oligonucleotide
      probe, NH1, hybridized only to amplification products from B. fragilis. PCR-dot
      blot hybridization based on nanH enabled detection of cells of B. fragilis in
      blood samples even when the number was as low as 2 x 10(3) colony-forming
      units/ml. These findings suggest that PCR-dot blot hybridization targeting nanH
      is a useful procedure for diagnosis of septicemia caused by B. fragilis when
      viable cells in blood cannot be detected by the traditional culture techniques.

PMID- 11286019
TI  - Clinical study of strangulation obstruction of the small bowel.
AB  - Early diagnosis of strangulation obstruction is very important for surgeons
      because delayed diagnosis often leads to severe complications. Thirty patients
      underwent an operation because of small bowel obstruction between April, 1993 and
      December, 1999. In the present study, we examined the differences in clinical
      findings between simple obstruction and strangulation obstruction. In addition,
      we examined the manifestation of systemic inflammatory response syndrome (SIRS)
      and whether it is useful for early diagnosis of strangulation obstruction, and
      whether it is correlated with the severity of ischemia due to strangulation.
      Tenderness was examined in all patients and signs such as abdominal irritation
      were detected more often in patients with strangulation obstruction than in the
      patients with simple obstruction. According to SIRS, the large number of the
      patients with strangulation obstruction showed SIRS before operation and the
      manifestation of SIRS correlated well with the length of the necrosis in the
      strangulated small bowel. We recognized the importance of anamnesis and clinical
      findings in examinations of small bowel obstruction, furthermore, it was
      suggested that SIRS should be the warning sign for strangulation obstruction.

PMID- 11286021
TI  - Molecular cloning of a cystatin from parasitic intestinal nematode,
      Nippostrongylus brasiliensis.
AB  - A novel member of the cystatin family, nippocystatin (NbCys), was identified from
      excretory-secretory (ES)-products of a nematode Nippostrongylus brasiliensis, and
      the cDNA was cloned and sequenced. The mRNA of NbCys was confirmed to be
      expressed in both larvae and adults of the parasite. NbCys was translated as a
      proform with a single domain for secretion and was detected as a 14-kDa mature
      form in ES-products of the adult worm. Recombinant protein of NbCys profoundly
      inhibited the activity of cysteine proteases such as cathepsin L and B, but not
      that of cathepsin D, an aspartic protease. Furthermore, the ES-products had also
      been confirmed to inhibit cysteine proteases. Taken together, NbCys may play a
      role in evasion of N. brasiliensis from host defense systems, since cysteine
      proteases are known to participate in immune systems of infected hosts.

PMID- 11286020
TI  - Role of innate immune cells in protection against Toxoplasma gondii at inflamed
      site.
AB  - The intraperitoneal infection with Toxoplasma gondii (T. gondii) caused
      accumulation of gamma delta T, NK, NK1.1+T-like (NKT) cells at inflamed sites. To
      clarify the roles of these cells in protection against T. gondii at the inflamed
      sites, BALB/c mice were depleted of gamma delta T, NK, NK and NKT cells by
      treatment with antibody against TCR-gamma delta, asialoGM1 or Interleukin-2
      receptor beta-chain (IL-2 R beta), respectively, prior to infection. Mice treated
      with anti-TCR-gamma delta monoclonal antibody (mAb) became more susceptible to
      infection, whereas mice treated with anti-IL-2R beta mAb acquired resistance.
      Treatment with anti-asialoGM1 Ab showed no effect. We previously reported that
      heat shock protein 65 (HSP65) in macrophages induced by gamma delta T cells plays
      an essential role in protective immunity against T. gondii infection, by
      preventing apoptotic death of infected macrophages. In the present study, we
      showed that treatment with anti-IL-2R beta mAb, but not with anti-asialoGM1 Ab,
      enhanced the HSP65 induction in macrophages, and inhibited Interleukin-4 (IL-4)
      expression in nonadherent peritoneal exudate cells. Furthermore, neutralization
      of endogenous IL-4 by anti-IL-4 mAb enhanced the HSP65 induction in macrophages.
      These findings suggest that NKT cells, but not NK cells, negatively regulate the
      protective immunity against T. gondii infection possibly by producing IL-4 and
      suppressing HSP65 induction.

PMID- 11286022
TI  - Inhibitory effects of bitter melon (Momordica charantia Linn.) on bacterial
      mutagenesis and aberrant crypt focus formation in the rat colon.
AB  - Antimutagenicity and chemopreventive activity of an 80%-ethanol extract of bitter
      melon (Momordica charantia Linn.) against the formation of azoxymethane (AOM)
      induced aberrant crypt foci (ACF) was investigated. The bitter melon extract was
      nonmutagenic and inhibited the mutagenicity of heterocyclic amines 2-amino-3,4
      dimethylimidazo[4,5-f]quinoline and 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine, and aflatoxin B1 in the Salmonella mutation assay. To examine the
      inhibitory effect of bitter melon on AOM-induced ACF formation, male F344 rats
      were fed various concentrations of the extract (0.1, 0.5, and 1.0 g/kg body
      weight) for five weeks during the initiation stage. One week after the
      administration of the plant extract, rats were subcutaneously given AOM at 15
      mg/kg body weight once a week for two weeks. Three rats in each group were
      sacrificed 12 hr after the second AOM injection to analyze DNA adducts, O6
      methylguanine (O6-meG) and N7-methylguanine in the liver and colon. The remaining
      rats were sacrificed 3 weeks after the second AOM injection to observe ACF. To
      examine the inhibitory effect of the extract on ACF formation in the
      postinitiation stage, rats were fed the extract at 0.1 and 1.0 g/kg body weight
      for 12 weeks starting two weeks after the second AOM injection. Treatment with
      bitter melon extract significantly inhibited ACF formation in the colon during
      the initiation stage and dose-dependently decreased the average of O6-meG DNA
      adduct in the colonic mucosa. During the postinitiation stage, bitter melon
      extract, at 1.0 g/kg body weight, significantly inhibited ACF formation in the
      colon, especially the formation of ACF with four or more crypts per focus. These
      findings suggest that bitter melon is a possible chemopreventive agent against
      colon carcinogenesis.

PMID- 11286023
TI  - Interferon-gamma activates outwardly rectifying chloride channels in the human
      bronchial epithelial cell line BEAS-2B.
AB  - The mechanism of increased chloride currents by inflammatory cytokine, interferon
      gamma (IFN-gamma), was investigated in cultured a human bronchial epithelial cell
      line (BEAS-2B) using cell-attached and inside-out patch configurations. The
      channel sensitive to chloride ion was activated by forskolin, an activator of
      adenylate cyclase, or 100 microM dibutyryl 5'-cyclic monophosphate in cell
      attached configurations. The conductance of this channel was 40 +/- 4 pS in
      symmetrical 150 mM chloride solution between membrane potentials of 0 to  mV, and
      this channel was blocked by 500 microM 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid (DIDS), suggesting that this channel was an outwardly rectifying
      chloride channel (ORCC). Treatment of 10-1000 U/ml IFN-gamma for 3 hours, but not
      IFN-alpha, significantly increased channel activities of ORCC, and this
      activation was observed at least 24 hours after treatment. Erythromycin, a
      macrolide antibiotic, at a concentration of 100 microM inhibited the activation
      of ORCC induced by IFN-gamma. The findings of the present study indicate that
      increased mucus secretion during inflammation might be partly due to activation
      of chloride permeability by cytokine and erythromycin might improve oversecretion
      of mucus from bronchial epithelium by blocking ORCC.

PMID- 11286024
TI  - [Insulin secretion and resistance during pregnancy in women with glucose
      intolerance].
AB  - OBJECTIVE: To investigate whether insulin secretion and resistance are different
      in glucose tolerant and intolerant women with normal pre-pregnant body mass index
      (BMI) during late pregnancy and to find out if there is association between
      gestational diabetes and insulin resistance syndrome. METHODS: On the basis of a
      4-hour oral glucose tolerance test (OGTT), 32 gestational diabetes mellitus (GDM)
      patients, 21 gestational impaired glucose tolerant (GIGT) patients, and 50 normal
      glucose tolerant (NGT) cases were selected from uncomplicated pregnant women.
      Those had normal pre-pregnant BMI who had a 1-hour 50-g glucose-screening test (>
      or = 7.2 mmol/L), performed between 24-28 weeks of gestation. During the OGTT,
      several indexes of insulin resistance, insulin secretion, lipid metabolism were
      measured in addition to the standard glucose measurements. RESULTS: Glucose area
      under curve (GAUC), insulin area under curve (IAUC), insulin sensitivity index
      (ISI) transformed to natural logarithm and triglycerides (TG) are all
      significantly higher (P < 0.05) in GDM women. The means of these indexes in GDM
      group are 26.3 mmol/L.h-1, 276.5 mU/L.h-1, 4.2 and 3.2 mmol/L, respeetively. On
      the other hand, however, the differences of these indexes (except TG) between
      GIGT and NGT women are not statistically significant. The ratio of IAUC/GAUC has
      an increasing trend from GDM group, GIGT group to NGT group (10.5, 11.4 and 11.7,
      respectively), but the difference is not statistically significant. Multiple
      correlation coefficient study demonstrated that ISI is significantly positively
      correlated with GAUC, IAUC and TG (P < 0.01). CONCLUSIONS: Compared with NGT
      women, GDM women has impaired insulin secretion, abnormally increased insulin
      resistance, and relatively dyslipidemia. GDM seems to be a component of the
      syndrome of insulin resistance that provides an excellent model for study and
      prevention in a relatively young aged group.

PMID- 11286025
TI  - [Analysis on maternal deaths from pregnancy complicated with acute abdominal
      diseases in Shanghai during 1989-1998].
AB  - OBJECTIVE: To raise the vigilance for pregnancy complicated with acute abdominal
      diseases and to reduce the maternal mortality rate. METHODS: A retrospective
      study was done. RESULTS: (1) The maternal mortality of pregnancy complicated with
      acute abdominal diseases was 1.31/10(5) in the period of 1989-1993, which was
      significantly higher than that in the period of 1994-1998 (0.71/10(5)). (2) The
      main cause of maternal deaths was misdiagnosis and the rate of misdiagnosis was
      72.7%. (3) Among the acute abdominal diseases, pregnancy complicated with
      pancreatitis ranked the first that accounted for 54.6%. CONCLUSIONS: For the
      purpose of reducing the mortality rate of pregnancy complicated with acute
      abdominal diseases, the correct diagnosis and proper treatment especially for
      those with acute pancreatitis are important.

PMID- 11286026
TI  - [Changes of maternal and umbilical serum nitric oxide in patients with the
      intrauterine growth retardation].
AB  - OBJECTIVE: To determine whether the levels of maternal and umbilical serum nitric
      oxide (NO) were changed in cases of intrauterine growth retardation (IUGR).
      METHODS: Fifteen pregnant women with fetuses of IUGR (IUGR group) and 25 normal
      pregnant women in late trimester (normal control group) were studied. Maternal
      and fetal umbilical venous blood were collected from all the cases. Serum NO2
      /NO3-, the end products of NO, were measured with the Griess reaction after
      reduction with nitrate reductase. RESULTS: Mean NO2-/NO3- values in maternal
      serum were (74.22 +/- 28.99) mumol/L in IUGR group and (56.71 +/- 22.81) mumol/L
      in the control. Umbilical serum NO2-/NO3- values were (39.73 +/- 24.65) mumol/L
      in IUGR group and (21.49 +/- 6.69) mumol/L in the control. Compared with the
      control, maternal as well as umbilical serum NO2-/NO3- in IUGR group were
      significantly higher (P < 0.05 and P < 0.001, respectively). The total nitrite
      levels in fetal circulation were lower than in maternal circulation in both
      groups (P < 0.05). CONCLUSIONS: Changes of NO in the pregnant women and their
      fetuses were due to the result of secondary complementary response in the
      patients with IUGR. The metabolic disorder of nitric oxide in maternal and fetal
      circulation may play an important role in pathogenesis of IUGR.

PMID- 11286027
TI  - [The complication of multiple system organs failure in pregnancy: a clinical
      analysis of 13 cases].
AB  - OBJECTIVE: To find out the features and causes of the complications of multiple
      system organs failure (MSOF) in pregnancy and increase the level of its
      prevention and treatment. METHODS: A retrospective study was carried out on 13
      cases with the complication of MSOF in pregnancy admitted between Feb 1992-Jun
      1999. RESULTS: There were two or more organs or systems function failure in the
      pregnancy. Four cases induced by infection, 5 cases induced by heart diseases, 3
      cases induced by pregnancy induced hypertension, 1 case induced by amniotic fluid
      embolism. 12 of 13 were cured. 1 was died. Among them one infant was died.
      CONCLUSIONS: During the treatment of pregnancy with multiple system organs
      failure, it is important to control the causes and inducements. It is forcible to
      terminate pregnancy in time and choose a best style of delivery. It is better to
      keep watch on saving multiple system organs function.

PMID- 11286028
TI  - [Effects of insulin-like growth factor-I and insulin-like growth factor binding
      protein 1 on development of ovarian follicles during superovulation cycle].
AB  - OBJECTIVE: To investigate the effects of insulin-like growth factor I (IGF-I) and
      insulin-like growth factor binding-protein 1 (IGFBP-1) on development of ovarian
      follicles during gonadotropin stimulation in in-vitro fertilization (IVF)
      program. METHODS: Enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay
      were used to determine the levels of IGF-I, IGFBP-1 and estradiol (E2) in serum
      and follicular fluid obtained during oocyte pick-up (OPU) in 32 IVF-embryo
      transfer cycles. RESULTS: (1) Serum IGFBP-1 levels increased with growth of
      follicles [(3.5 +/- 1.0) micrograms/L during OPU, (2.1 +/- 0.5) micrograms/L
      before stimulation, P < 0.05]; follicular fluid (FF) IGFBP-1 levels were
      significantly higher than those of matched serum levels [(77.7 +/- 26.7)
      micrograms/L, (3.5 +/- 1.0) micrograms/L respectively P < 0.001]; Serum IGFBP-1
      levels were positively correlated with developing of follicle numbers (r = 0.48,
      P < 0.05). (2) There were no significant changes of serum IGF-I levels before and
      after superovulation, neither was there between serum and follicle fluid [(103.7
      +/- 39.2) micrograms/L, (105.9 +/- 36.8) micrograms/L, (108.9 +/- 19.1)
      micrograms/L respectively P > 0.05]. Significant positive correlation was found
      between serum IGFBP-1 and serum E2[(3.5 +/- 1.0) micrograms/L, (3,293 +/- 1,361)
      pmol/L, r = 0.41, P < 0.05). CONCLUSIONS: During superovulation serum total IGF-I
      levels do not change. However changes of serum IGFBP-1 levels may play a
      complementary role in regulation of follicular development by altering free IGF-I
      levels.

PMID- 11286029
TI  - [Changes of T lymphocyte and CD4+ T helper subsets in peripheral blood from women
      with unexplained recurrent spontaneous abortion].
AB  - OBJECTIVE: To investigate the relationship between occurrence of unexplained
      recurrent spontaneous abortion(URSA) and immune function of T lymphocytes.
      METHODS: T lymphocyte subsets and CD4+ T helper subsets (including T helper 1 and
      T helper 2 cells) in peripheral blood from 30 cases with URSA and 24 healthy
      women (controls) were detected by enzyme-linked immunospot assay (ELISPOT).
      RESULTS: The percentage of CD4+ positive T lymphocytes in URSA group was higher
      than that in the controls (60% vs 45%, P < 0.05). Compared with the normal group,
      the percentage of Th1 cells increased (26% vs 14%, P < 0.01) but the percentage
      of Th2 cells decreased (7% vs 20%, P < 0.05), the ratio of Th1 to Th2 increased
      (3.80 vs 0.73, P < 0.01) in the URSA group. CONCLUSIONS: The occurrence of URSA
      might be associated with proliferation of the CD4+ positive T cells and
      enhancement of cellular immune function mediated by Th1 cells.

PMID- 11286030
TI  - [Effects of epimedium on the expression of interleukin-6 messenger ribonucleic
      acid in bone of ovariectomized rat].
AB  - OBJECTIVE: To investigate the effects of the traditional herb-epimedium on the
      expression of interleukin-6 (IL-6) mRNA in bone of ovariectomized rat. METHODS:
      Forty female rats were randomly allocated into 4 groups, 10 in each:
      ovariectomized (OVX) group, sham operation group, OVX followed by epimedium
      (group 3) or nilestriol (group 4) for 3 months respectively. All rats were then
      sacrificed, and total RNA were directly isolated from their right tibia.
      Interleukin-6 mRNA expression was detected by relative semiquantitative reverse
      transcription-polymerase chain reaction technique. Lumbar bone mineral density
      (BMD) was measured by dual-energy X ray absorptiometry before sacrifice. RESULTS:
      The BMD of epimedium group was significantly higher than that in the OVX group (P
      < 0.05). On the contrary, the IL-6 mRNA expression level of epimedium group was
      significantly lower than that in the OVX group (P < 0.01), but higher than those
      in the sham and nilestrial group (P < 0.01). CONCLUSIONS: IL-6 may play a role in
      the pathogenesis of postmenopausal teoporosis. Epimedium can inhibit the
      expression of IL-6 mRNA, which may contribute to its anti-resorptive effect.

PMID- 11286031
TI  - [Study on women with abnormal uterine bleeding treated by hysteroscopic electric
      resection].
AB  - OBJECTIVE: To evaluate the efficacy, prognosis and influences of hysteroscopic
      electrosurgery in treating abnormal uterine bleeding (AUB). METHODS: Eighty two
      women with AUB were treated by hysteroscopic electric resection. Among them, 48
      cases had submucous myomas, 29 cases endometrial polyps, 4 cases dysfunctional
      uterine bleeding, and 1 case had submucous myoma and endometrial polyps. RESULTS:
      The mean time of follow-up was 25.5 months. The effective rate of menstrual flow
      ameliorated was in 91.5% of the patients. Yet, the percentage of the effective
      rate was decreased gradually with time. The improved effective rates of
      dysmenorrhea, midcycle pain, premenstrual symptoms and perimenstrual symptoms
      were 83.3%, 60.0%, 60.0% and 62.7% respectively. The effective rate of total
      symptoms improved in endometrial thickness with < or = 5 mm was 91.3%, and that
      in endometrial thickness with > 5 mm was 63.6%. There is a significant difference
      between in endometrial thickness with < 5 mm and in endometrial thickness with <
      5 mm (P < 0.05). The effective rate of total symptoms improved with drugs
      suppressing endometrium used in perioperation was 93.8%, and that with no drug
      used was 72.0%. There is also a significant difference between drug used and no
      drug used groups (P < 0.05). CONCLUSIONS: Hysteroscopic electric resection in
      treating AUB improves not only menstrual flow but also perimenstrual symptoms.
      The effectiveness and prognosis of this operation may be related to endometrial
      thickness and medical treatment.

PMID- 11286032
TI  - [The study on biologic manner and clinical management of intravenous uterine
      leiomyoma].
AB  - OBJECTIVE: To investigate the biologic manner of intravenous uterine myoma and
      the clinical management. METHODS: Analysed 11 cases of intravenous leiomyoma
      retrospectively from 1994 to 1998, of which all specimens of intravenous
      leiomyoma were confirmed by pathologic examination. The estrogen receptor was
      measured by immunohistochemistry. RESULTS: Nine patients (81.8%) presented
      menorrhagia, two patients (18.2%) appeared anemia. The size of uterus more than
      three pregnancy months was seen in seven cases (63.6%), of which six patients
      (6/7) showed uterine multiple nodule and abundant blood flow by ultrasound
      compared with those whose uterine size smaller than three pregnancy months (P >
      0.05). The correct diagnosis before operation was 0 percent, 63.6% of the
      patients was diagnosed during operation (P < 0.05). Seven patients (63.6%) had
      classical pathological appearance of intravenous leiomyoma. Positive estrogen
      receptors were detected in six patients. One patient (9.1%) was recurred.
      CONCLUSIONS: Uterine intravenous leiomyoma has typical clinical and pathologic
      feature. The adverse biologic manner and the clinical treatment are related to
      prognosis.

PMID- 11286033
TI  - [Clinical study of four cases with malignant gestation trophoblastic tumor after
      mifepristone abortion].
AB  - OBJECTIVE: To describe the clinical characteristics of malignant gestational
      trophoblastic tumor after medical abortion used by mifepristone combined with
      misoprostol and its diagnosis and differential diagnosis from incomplete
      abortion. METHODS: Four cases with malignant gestational trophoblast tumor after
      medical abortion were presented focusing on the clinical manifestation and the
      methods of diagnosis and differential diagnosis. RESULTS: Irregular vaginal
      bleeding and abnormal high level of beta-human chorionic gonadotropin (hCG) in
      plasma were the common manifestation of the gestational trophoblast tumour and
      incomplete abortion after medical abortion. However, beta-hCG of the former after
      curettage was still higher by dynamic monitoring. Malignant gestational
      trophoblast tumor showed rich blood flow signal and low blood flow resistance
      index (RI, RI < 0.5) in uterus in color doppler echography, digital subtraction
      angiography (DSA) with abnormal enlargement of the arteria of uterine,
      arteriovenous fistula beside the uterine were the main characteristics of
      malignant gestational trophoblast tumour. CONCLUSIONS: Pay attention to the early
      stage malignant gestational trophoblast tumour among patients with abnormal
      vaginal bleeding after medical abortion. beta-hCG and DSA were the most effective
      methods to diagnose and differentially diagnose choriocarcinoma from the
      incomplete abortion among the patients with abnormal vaginal bleeding after
      medical abortion.

PMID- 11286034
TI  - [Adenovirus-mediated herpes simplex virus thymidine kinase gene transference and
      combined drug therapy leads to apoptosis of human epithelial ovarian cancer
      cells].
AB  - OBJECTIVE: To evaluate the treatment and apoptosis effect of adenovirus-mediated
      herpes simplex virus thymidine kinase (HSV1-tk) gene transference followed by
      administration of ganciclovir (GCV) and acyclovir (ACV) on ovarian epithelial
      cancer cells. METHODS: Recombinant adenovirus was amplificated and purified by
      routine method. The expression of HSV1-tk gene was assayed by polymerase chain
      reaction (PCR). The efficiency of recombinant Advtk transference was evaluated.
      The cytotoxicity efficacy of TYK cells that carry HSV1-tk gene was evaluated
      followed by GCV, ACV administration after the transference of Advtk. The changes
      and apoptosis of TYK cells that carry HSV1-tk gene were observed by means of
      analysis of DNA fragmentation and electronic microscopy. RESULTS: Adenovirus was
      amplificated and purified in large amount. PCR assay showed 404 bp special band.
      When the multiplicities of infection (MOI) was 100, the transduction rate was
      98.9%. The inhibition rates of TYK cells that carry HSV1-tk gene increased with
      the increase of MOI when the same concentration of GCV, ACV were given. When the
      MOI was same, the inhibition rates were also increased with the increase
      concentration of GCV, ACV. Apoptosis of TYK cells that carry HSV1-tk gene after
      administration of GCV was observed by means of analysis of DNA fragmentation and
      electronic microscopy. CONCLUSIONS: The HSV1-tk gene can effectively transferred
      into TYK cells by recombinant replicated-deficient adenovirus vector, GCV, ACV
      can effectively kill TYK cells that carry HSV1-tk gene in vitro. Apoptosis may be
      the mechanism of the killing effect.

PMID- 11286035
TI  - [Protein expression of human progesterone receptor isoforms A and B in uterine
      leiomyoma].
AB  - OBJECTIVE: To investigate the role of two isoforms of human progesterone receptor
      A (hPR-A) and B (hPR-B) in the development of uterine leiomyoma, their
      distribution and expression in leiomyoma were detected. METHODS: The tissues of
      leiomyoma and normal myometrium from 30 uteri, which were excised for leiomyoma,
      were used for the localization and quantification of protein of the two isoforms.
      Immunohistochemistry and Western blot were applied respectively. RESULTS: Both
      hPR-A and hPR-B were nuclear receptors. Concentrations of hPR-(A + B) and hPR-A
      in leiomyoma were higher than those in normal myometrium (295,796 +/- 90,856,
      256,275 +/- 98,560; P = 0.042, P = 0.000,563). Both isoforms were presented in
      leiomyoma and normal myometrium, with a consistent dominance of hPR-B over hPR-A.
      More expression of hPR-A was found during secretive phase than proliferative
      phase, not only in leiomyoma but also in normal myometrium (P = 0.037, P =
      0.024). CONCLUSIONS: The development of uterine leiomyoma seems to be related
      with the progesterone receptor isoforms, especially hPR-A.

PMID- 11286036
TI  - The surgical approach to cerebellopontine angle lipomas.

PMID- 11286037
TI  - Welcoming normative data for Wisconsin Card Sorting Test.

PMID- 11286038
TI  - Study Group of Bioethics and Palliative Care in Neurology: program document.

PMID- 11286039
TI  - Efficacy and tolerability of sumatriptan in the treatment of multiple migraine
      attacks.
AB  - This cross-over, double blind, randomized, multicentre study evaluated the
      consistency of efficacy and safety of oral sumatriptan in 233 migraneurs. The
      patients received 50 mg oral sumatriptan or placebo for the treatment of 12
      migraine attacks. Within each group of 4 attacks, three were treated with
      sumatriptan and one with placebo, according to a randomization list. Over all the
      attacks, the efficacy rate was statistically significant for sumatriptan against
      placebo at 2 or 4 hours (2 hours: sumatriptan 60%, PLO 38%, p < 0.001; 4 hours
      sumatriptan 79%, PLO 47%, p < 0.001). Oral sumatriptan was similarly effective at
      relieving the associated symptoms and at reducing clinical disability in most
      attacks. The incidence of adverse events did not differ between treatment groups.
      All the events recorded were mild to moderate as intensity and resolved
      spontaneously.

PMID- 11286040
TI  - Wisconsin card sorting test: a new global score, with Italian norms, and its
      relationship with the Weigl sorting test.
AB  - The Wisconsin card sorting test and the Weigl test are two neuropsychological
      tools widely used in clinical practice to assess frontal lobe functions. In this
      study we present norms useful for Italian subjects aged from 15 to 85 years, with
      5-17 years of education. Concerning the Wisconsin card sorting test, a new
      measure of global efficiency (global score) is proposed as well as norms for some
      well known qualitative aspects of the performance, i.e. perseverative responses,
      failure to maintain the set and non-perseverative errors. In setting normative
      values, we followed a statistical methodology (equivalent scores) employed in
      Italy for other neuropsychological tests, in order to favour the possibility of
      comparison among these tests. A correlation study between the global score of the
      Wisconsin card sorting test and the score on the Weigl test was carried out and
      it emerges that some cognitive aspects are not overlapping in these two measures.

PMID- 11286041
TI  - Quantitative assessment of cerebral vascular reserve by means of transcranial
      Doppler ultrasound and rebreathing maneuver: bedside test and mathematical
      modeling.
AB  - Cerebral vascular reserve was measured by means of the transcranial Doppler (TCD)
      technique from carbon dioxide (CO2) tests, in healthy individuals and patients
      with unilateral internal carotid artery (ICA) occlusion. The percentage changes
      in middle cerebral arteries blood flow velocity (VMCA) per mmHg of pCO2
      variations (reactivity index, RI) were separately computed during hypocapnia and
      hypercapnia, the latter obtained by a rebreathing maneuver. Clinical data have
      been compared with predictions obtained using an original mathematical model of
      intracranial dynamics, in order to search a theoretical explanation of the
      hemodynamic events observed during clinical testing. This analysis has also been
      considered in order to support the choice between different CO2 tests for
      quantitative assessment of vascular reactivity. Clinical data and model
      simulations agree in showing that side-to-side reactivity differences (Irel)
      measured from hypercapnia test allow a good discrimination of patients with poor
      compensatory capacity. They suggest that an Irel significantly greater than 30%
      after hypercapnia test can be considered indicative of patients with poor
      compensatory capacity. These preliminary results encourage a long-term follow-up
      of cerebral vascular reserve by means of TCD during "rebreathing test", for
      selecting patients with poor vascular reserve that may benefit from brain
      revascularization.

PMID- 11286042
TI  - Can seizures be the only manifestation of transient ischemic attacks? A report of
      four cases.
AB  - Several studies have investigated the frequency of epileptic seizures following
      ischemic strokes and transient ischemic attacks (TIAs). Little attention has been
      paid to the possibility that seizures may be precipitated by TIAs. We examined if
      seizures can be the only symptom of a TIA and how often this might occur. We
      performed a retrospective analysis of clinical charts and electroencephalograms
      of 160 consecutive patients evaluated for a first-ever seizure from January 1997
      to December 1999 at Belluno General Hospital. From January to May 2000, 19 more
      first-ever seizure patients were evaluated directly. Four patients (2%) had
      seizures in the presence of important risk factors for ischemic stroke (atrial
      fibrillation in two patients, atrial fibrillation and ventricular mural thrombus
      in one patient, hemodynamically significant left carotid stenosis in one
      patient). Seizures were not accompanied by other neurological deficits or brain
      lesions on CT or MRI. As risk factors for brain ischemia are frequent in the
      general population not developing seizures, our results do not prove that the
      occurrence of seizures was more than casual in these patients. Yet they indicate
      that in a small percentage of patients, seizures can occur in a context highly
      suggestive of TIA, with no other focal deficits.

PMID- 11286043
TI  - Cognitive function and neurophysiological evaluation in early-treated hypothyroid
      children.
AB  - In this study, we assessed cognitive function and neurophysiological development
      in congenitally hypothyroid (CH) children. We performed a cross-sectional study
      at the outpatient Pediatric Clinic and Department of Neurophysiology at San
      Raffaele Hospital, Milan. The study enrolled 25 CH patients (6.00-10.83 years of
      age) detected by neonatal screening, and 34 healthy control children (4-11 years
      of age). Patients and controls had comparable scores at neuropsychological tests
      (WISC-R), and at auditory P300 tests. In contrast, we found significantly longer
      LLSEP latencies in CH patients (p < 0.03). CH patients treated 30 days after
      birth showed lower scores at neuropsychological tests, but not at
      neurophysiological tests, compared to patients who started the replacement
      therapy earlier. Patients with more severe fetal hypothyroidism (T4 levels at
      diagnosis < or = 2 micrograms/dl) had lower neuropsychological scores, and
      similar neurophysiological results, compared with patients with moderate fetal
      hypothyroidism. The severity of fetal hypothyroidism and early treatment
      influence the mental outcome of CH patients. Neurophysiological results show that
      central nervous system damage occurs in some patients despite early treatment.

PMID- 11286044
TI  - New alternative agents in essential tremor therapy: double-blind placebo
      controlled study of alprazolam and acetazolamide.
AB  - Propranolol and primidone are widely used, effective agents in essential tremor
      although they are not tolerated by all patients. In the present study, the
      effectiveness of alprazolam, a triazole analog of benzodiazapine class, and
      acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic
      treatments for essential tremor. We studied 22 patients with essential tremor in
      a double-blind, cross-over, placebo-controlled design. The patients received in
      random order alprazolam, acetazolamide, primidone and placebo for four weeks,
      each separated by a two-week washout period. The study demonstrated that
      alprazolam was superior to placebo and equipotent to primidone, whereas there was
      no statistically significant difference between acetazolamide and placebo. The
      mean effective daily dose of alprazolam was 0.75 mg and there was not any
      troublesome side effect reported by the patients on alprazolam. Alprazolam can be
      used as an alternative agent in elderly essential tremor patients who can not
      tolerate primidone or propranolol.

PMID- 11286045
TI  - The physician-patient relationship in amyotrophic lateral sclerosis.
AB  - The principal models of the physician-patient relationship are analysed in terms
      of their historical development. An outline is given of the clinical,
      psychological and ethical particularities of the approach to patients with
      amyotrophic lateral sclerosis. The peculiarities of this disease are so exclusive
      that they do not resemble other progressive diseases with a negative prognosis,
      and therefore require an equally exclusive approach to the physician-patient
      relationship. This approach should not only be informative, scientific and
      interpretative-deliberative, but must simultaneously be founded on a solid
      therapeutic alliance aimed at seeking the best interests of the patients while
      respecting their autonomy as well as their "good" (not only in the sense of
      physical well-being, but also in terms of respect for their personal values).
      This is the only way to confront the conflicts that inevitably arise (especially
      in advanced stages of the disease) without the risks associated with a desire to
      escape or to adopt extreme solutions (such as euthanasia and therapeutic
      insistence) and without the risk of burn-out.

PMID- 11286046
TI  - Anatomical and psychological mechanism of reduplicative misidentification
      syndromes.
AB  - Reduplicative misidentifications syndromes (RMS) are rare memory disorders
      characterized by the subjective conviction that a place, person or event is
      duplicated. Even if RMS often follow a right frontal lesion, several studies have
      stressed the importance of bilateral hemispheric pathology. Moreover, from a
      psychological perspective, there is uncertainty if this symptom should be
      considered just as a kind of confabulation or if it should be associated with
      personal psychosocial and behavioral aspects. We report a patient who developed
      normal pressure hydrocephalus and RMS one year after a post-traumatic right
      frontal lesion. At the first neuropsychological evaluation, we found mild
      impairment of all functions, associated with the presence of reduplicative
      paramnesia. After the ventricle-peritoneal shunt intervention, we observed a
      progressive improvement of all functions but the frontal ones. The memory deficit
      became less specific and the RMS disappeared. We therefore postulate that a focal
      right frontal lesion is not sufficient to cause RMS per se. Our clinical report
      suggests that paramnesic events held on reasonable ground, not being just a kind
      of confabulation.

PMID- 11286047
TI  - Therapeutic considerations in cerebellopontine angle lipomas inducing hemifacial
      spasm.
AB  - Lipoma is a very rare tumour at the cerebellopontine angle. We report a case of
      incomplete hemifacial spasm, associated with a lipoma involving and compressing
      both facial and acoustic nerves at their origin in the brainstem. The patient was
      treated with medical therapy (botulinum toxin A) and surgery. We present a review
      of the last ten years of the literature, with particular regard to management.

PMID- 11286048
TI  - Clinical neurophysiology: the hard way to a better future.

PMID- 11286049
TI  - Phosphorus removal characteristics of a combined AS-biofilm process cultured by
      different COD/TP ratios.
AB  - The COD/TP ratio of influent is an important parameter for the phosphorus removal
      in a biological nutrient removal (BNR) process. In this study, we investigated
      the phosphorus removal and denitrification characteristics of a combined
      activated sludge-biofilm process, as cultured by different influent COD/TP ratios
      ranged from 12 to 120. Experimental results indicated that, when COD/TP ratios
      exceeded 30, the removal efficiencies of COD, TN and TP were 98%, 76% and 100%,
      respectively. However, when the COD/TP ratios were less than 30, the COD removal
      efficiency still surpassed 98%, but the TP removal efficiency decreased to 41%
      and 31.8% when COD/TP ratios were 20 and 12. Moreover, the weight percentage of
      phosphorus in the sludge attained a stable value when the COD/TP ratios were
      below 30. The maximum weight percentage of phosphorus in the sludge was found to
      be about 6% and, under this condition, the critical COD/TP ratio of influent was
      30 of the process under a sludge retention time of 12 days. Although the amount
      of accumulated PHAs per mg phosphate released (gamma PHA/PO4) remained stable
      between a COD/TP ratio of 30 to 120, it increased with a decreased of the COD/TP
      ratio when the COD/TP ratio was less than 30.

PMID- 11286050
TI  - Methane oxidation in three Alberta soils: influence of soil parameters and
      methane flux rates.
AB  - Current concern over the potentially negative impacts of climate change has
      brought attention to anthropogenic sources of methane, a primary greenhouse gas.
      Two such emission sources are methane leakage at heavy oil wells and sanitary
      landfills. At both of these sources, substantial quantities of methane could
      potentially be oxidised by methanotrophic microbes living in soils. Optimisation
      of this phenomenon may serve as an inexpensive technique for reducing methane
      emissions. Soil column and batch incubation experiments were performed on a
      landfill loam, an agricultural loam and a sedge peat to gain a better
      quantitative understanding of the biological and physical processes limiting CH4
      oxidation in soils that undergo the freeze-thaw cycles associated with northern
      climates. Moisture content emerged as a critical variable that can limit a soil's
      CH4 oxidation potential. For example, the oxidation rate of the agricultural soil
      was seen to increase by an order of magnitude after increasing its moisture
      content from 6% to 10% of its dry weight.

PMID- 11286051
TI  - The impact of residual coagulant on downstream treatment processes.
AB  - A series of jar tests were undertaken to optimise for suspended solids (SS) and
      phosphorus removal from raw wastewater. The residual metal concentration in the
      settled wastewater from the jar test experiments and the residual concentration
      from the optimum doses plus two higher doses were selected for investigation. The
      identified levels of residual metal were fed into a four lane activated sludge
      pilot plant to investigate the impact of metal concentration on (i) activated
      sludge performance and (ii) sludge production and characteristics. Optimum pre
      precipitation studies showed residual ion concentrations of 1.68 and 3.46 mg l-1
      for Fe(III) and Al(III) respectively. At these levels %P removal increased by
      approximately 25 and 60% respectively. NH3 removal decreased by approximately 20
      and 34% in the activated sludge treatment process. Chemically dosed biomass had a
      significantly lower oxygen uptake rate than the control which was accompanied by
      a reduction in VSS; 10% for Fe(III) and 17% for Al(III). Changes in sludge
      characteristics were also observed. Chemical sludge had a greater settleability
      but a lower dewaterability than biological sludge. Sludge floc morphology was
      characterised which showed chemical flocs to be consistently smaller and visually
      denser than biological sludge flocs. The work presented in this paper considers
      the impact of residual iron and aluminium coagulants on downstream treatment
      processes.

PMID- 11286052
TI  - Mathematical modeling of electrochemical remediation for soils under
      galvanostatic conditions.
AB  - This work proposes a mathematical model for the electrochemical remediation of
      clayey soils based on the total volume concept for a two-phase system. The
      mathematical formulation was done including contributions from theories for:
      groundwater, membranes, porous electrodes and environmental soil chemistry. The
      resulting model accounts for: free and complexed species in the soil matrix and
      the pore solution; chemical reactions taking place on either phase and/or between
      phases; a dynamic soil surface charge affected by the ion content of the pore
      solution; and electroneutrality of the total volume. Soil surface charge was
      included in a modified Ohm's law (voltage gradient) and in a modified Schlog's
      law (convective movement). Numerical implementation was done using orthogonal
      collocation on finite elements for spatial derivatives, and forward finite
      differences for time derivatives. Visual Fortran supported by IMSL subroutines
      was used for computer simulation. Model predictions were successfully compared
      with reported experimental data. Also, an analysis of pH profiles through the
      soil is provided for conditions when parameters including hydrostatic head,
      applied current density and initial pH are modified.

PMID- 11286053
TI  - Arsenic characterisation in industrial soils by chemical extractions.
AB  - The purpose of this research was to find a reliable and easy to use method to
      characterise As in iron-rich industrial or mining site soils. In this objective
      classical sequential extraction schemes and single extractions with EDTA and
      phosphate solutions were used. Results showed that classical Tessier's scheme
      overestimated residual As. A scheme specific to anionic species was also not
      really suitable to evaluate As distribution in these iron-rich soils. A more
      complex scheme using specific iron reagents indicated a correlation between iron
      dissolution and arsenic leaching and these results were confirmed by single
      extractions with EDTA and oxalate solutions. Finally a simplified and less time
      consuming scheme was established, tested on diverse industrial soils and
      validated on a certified sediment reference material. It allowed evaluation in 24
      hours of the easily extractable fraction, amount solubilized under reducing
      conditions and As strongly bound to the soil.

PMID- 11286054
TI  - Removal of toluene in gas streams by a fibrous-bed trickling filter.
AB  - A novel fibrous-bed trickling filter was developed to remove toluene present in
      contaminated air. Pure culture of Pseudomonas putida F1 was attached on fibrous
      bed and utilized toluene as the carbon source. Experimental results indicated the
      removal efficiency decreased with the increase of inlet concentration. In
      general, the removal efficiency of toluene was greater than 90% when the inlet
      loading capacity was below 70 g m-3h-3. The elimination capacity increased with
      increasing inlet loading capacity, but the increased rate decreased gradually.
      When the inlet loading capacity increased to 300 g m-3h-1, the elimination
      capacity could approach to 130 g m-3h-1. The first order kinetics model was
      useful to describe the removal of toluene in this filter and an excellent linear
      relationship was found between the apparent first order parameter and inlet
      concentration (ranging from 1.2 g m-3 to 3.5 g m-3). Also, the performance of
      fibrous-bed trickling filter was relatively stable during the four-month period
      of continuous operation. Slight clogging phenomena of filters were observed only
      under high loading capacity.

PMID- 11286055
TI  - Evaluation of porous ceramic as microbial carrier of biofilter to remove toluene
      vapor.
AB  - Three kinds of porous ceramic microbe media are fabricated from fly ash,
      diatomite and a mixture of fly ash and diatomite powders. Water holding capacity,
      density, porosity, pore size and distribution, compressive strength and micro
      structure of each of the fabricated media are measured and compared. The fly ash
      and diatomite mixture ceramic is evaluated as the best biofilter medium among the
      three media because of its high compressive strength. It is selected as an
      experimental biofilter medium inoculated with thickened activated sludge. The
      laboratory scale biofilter was operated for 42 days under various experimental
      conditions varying in inlet toluene concentration and flow rate of contaminated
      air stream. The experimental result shows that the removal efficiency reaches up
      to 96.6% after 4 days from the start-up. Nutrient limitation is considered as a
      major factor limiting biofilter efficiency. Biofilter efficiency decreases
      substantially at the build-up of backpressure, which is largely due to the
      accumulation of excess VSS within the media. Periodic backwashing of the
      biofilter is necessary to remove excess biomass and attain stable long-term high
      removal efficiency. The bed needs to be backwashed when the overall pressure drop
      becomes greater than 460.6 Pa at space velocity of 100 h-1. A maximum flow rate
      of 444.85 g m-3hr-1 of toluene elimination by the mixture ceramic biofilter,
      which is higher than the previously reported values. This indicates that the fly
      ash and diatomite mixture ceramic biofilter can be effectively applied for
      removing toluene vapor.

PMID- 11286056
TI  - Oxygen transfer characteristics in a pilot scale surface aeration vessel with
      Simcar aerator.
AB  - The volumetric mass transfer coefficient, KLa, was determined by dynamic method
      in a surface aerated pilot scale squared vessel up to 0.531 m3 equipped with
      Simcar type impeller. Through surface aeration, the oxygen transfer
      characteristics were investigated with the variations of operating variables such
      as stirring speed, impeller diameter, liquid height and power input per liquid
      volume (P0/V). It was seen from the results of different oxygen concentration
      absorption that the dynamic method might lead to errors in KLa when air was used
      for absorption. To provide reliable KLa values measured by dynamic, the KLa data
      using pure oxygen were used and confirmed with feeding steady-state method (FSM).
      As expected, KLa depends on P0/V, impeller size and liquid height. However, for
      Simcar type impeller, the KLa shows linear dependency on P0/V in contrast to
      majority of correlations reported in the literature which shows KLa variation of
      (P0/V)0.65 for disk type impeller. Moreover, it was interesting to find that the
      bubble behaviors inside the vessel computed by computational fluid dynamics (CFD)
      could explain qualitatively the KLa changes with operating variables. For the
      purpose of scale-up procedures, the empirical correlations for predicting KLa
      were developed within +/- 2% accuracy.

PMID- 11286057
TI  - Using of surfactant modified Fe-pillared bentonite for the removal of
      pentachlorophenol from aqueous stream.
AB  - The first part of this work considers the preparing of the adsorbent type Montm
      FeOH-CTAC. After purification of two types Algerian bentonites (Maghnia and
      Mostaghanem) and preparation of cationic polyhydroxy ferric solution, we have
      optimized following parameters: CTAC/Montm.-FeOH = 7 mmol.g-1 and pH = 3.4, in
      order to obtain the adsorbent with maximum uptake of PCP. The study of the
      different experimental equilibrium isotherms showed clearly the high efficiency
      of these new adsorbents toward PCP, with significant quantities adsorbed
      especially onto Maghnia samples in acidic environment. Using two mathematical
      models Langmuir and Freundlich was found to be the Freundlich the best fitted. A
      comparative study of PCP adsorption onto the two modified clays and an activated
      carbon in the same conditions has been done.

PMID- 11286058
TI  - Effective combination of microfiltration and intermittent ozonation for high
      permeation flux and VFAs recovery from coagulated raw sludge.
AB  - This research was conducted to investigate the effect of intermittent ozonation
      on permeation flux recovery and production for soluble organic materials in a
      membrane-coupled anaerobic VFAs fermenter (MCAVF) system. Flux recovery ratio
      exceeded 80% with 22.2 gO3 l-1 of ozone injection and then showed nearly 95% with
      43 gO3 l-1 in batch experiment. Under the same ozone concentration, extending
      contact time was more effective than increasing bubbling dose rate for flux
      recovery. In continuous-flow operation, the value of average permeation flux was
      0.69 m3 m-2 d-1 during without ozonation period, while average permeation flux
      for 70 days with intermittent ozone bubbling was 1.17 m3 m-2 d-1 that corresponds
      to 1.7 times that with no ozonation period. Moreover, in spite of intermittent
      ozone bubbling for 70 days, significant inhibition was not observed for volatile
      fatty acids (VFAs) producing bacteria and VFAs production. It was found that the
      average value of [permeates total organic carbon (TOC) concentration: Influent
      TOC concentration] with ozonation period was about 1.5 times higher than that of
      no ozonation period. Consequently, it is believed that a membrane-coupled
      anaerobic VFAs fermenter (MCAVF) process combined with intermittent ozonation is
      suitable to overcome the flux decline of membrane and simultaneously is useful to
      the recovery of soluble organic materials from coagulated raw sludge.

PMID- 11286059
TI  - Effects of pretreatment on physical and ion exchange properties of natural
      clinoptilolite.
AB  - Four pretreatment procedures have been applied to natural clinoptilolite to
      establish the influence of the pretreatment process on the properties of the
      material under investigation. Modification of material properties is imposed for
      its use in wastewater treatment via ion exchange processes. Batch pretreatment
      procedures as well as continuous flow column have been studied by using sodium
      chloride, sodium hydroxide and nitric acid solutions in deionized water.
      Measurements of the effective capacity, the diffusion coefficient in the solid
      state and examination of the crystal structure have been employed to assess the
      effect of each specific pretreatment on the material under test. The effective
      capacity is improved in all cases, by a factor of 2.4 to 3.6, while the diffusion
      coefficient values depend strongly on the type of pretreatment used and fall in
      the range of 0.03-1.37 x 10(-8) cm2s-2 at 20 degrees C. The crystal structure
      remains unaltered as evidenced by XRD measurements.

PMID- 11286060
TI  - Adsorption of the organic fraction of a tannery sludge by means of organophilic
      bentonite.
AB  - Two different organophilic bentonites obtained by cationic exchange with
      benzyldimethyloctadecylammonium chloride and trimethyloctadecylammonium chloride
      have been used to adsorb the organic fraction of a tannery sludge. The exchange
      process was carried out to different extents to obtain bentonite samples with
      different organophilicities and different interlayer spacings. Before adsorption,
      the organic matter was extracted by contacting the sludge with a Ca(OH)2
      saturated solution. The adsorption capacity was found to increase with the amount
      of ammonium salt exchanged for both bentonites, but the one exchanged with
      benzyldimethyloctadecylammonium chloride proved to be more active: up to about
      80% TOC could be removed from the contacting solution. The adsorption of the
      organic matter caused a further increase of the bentonite interlayer spacing. In
      both cases, the adsorption isotherms were found to be of cooperative type, due to
      weak adsorbent-adsorbate interactions at low loading followed by increasing
      adsorbate-adsorbate interactions at increasing loading. The results may be
      applied to tannery sludge stabilization by cementitious systems.

PMID- 11286061
TI  - Effect of hydraulic loading rate on acidogenesis in a membrane-coupled anaerobic
      VFAs fermenter.
AB  - A membrane-coupled anaerobic VFAs fermenter (MCAVF) was operated with five
      different hydraulic loading rates (3, 2, 1, 0.5 and 0.25 day-1) to evaluate its
      influence on acid phase VFAs production from coagulated raw sludge. Results show
      that C2 to C5 volatile fatty acids were formed as predominant compounds. At
      constant solids retention time (SRT) of 10 days, VFAs production ratio moderately
      increased over the range of hydraulic loading rate (HLR) of 3 day-1 to 2 day-1,
      but significantly decreased at other HLR conditions. First order hydrolysis rate
      constant decreased with a decrease in HLR. The relatively high degradation
      percentages of carbohydrate and protein were observed, ranging from 25 to 47%, 27
      to 47%, respectively. However, lipid and fiber component were degraded at much
      lower ratio than the previous other two organic materials. On the other hand,
      despite some variation in the minor acids in five HLR cases, VFAs speciation
      appeared to be independent of HLR. The results obtained emphasize that; at least
      in the range investigated, the optimal HLR for VFAs production and recovery from
      coagulated raw sludge is in the range of 2 day-1 and 1 day-1.

PMID- 11286062
TI  - Ground water and climate.

PMID- 11286064
TI  - Atrazine retention and degradation in the vadose zone at a till plain site in
      central Indiana.
AB  - The vadose zone was examined as an environmental compartment where significant
      quantities of atrazine and its degradation compounds may be stored and
      transformed. The vadose zone was targeted because regional studies in the White
      River Basin indicated a large discrepancy between the mass of atrazine applied to
      fields and the amount of the pesticide and its degradation compounds that are
      measured in ground and surface water. A study site was established in a
      rotationally cropped field in the till plain of central Indiana. Data were
      gathered during the 1994 growing season to characterize the site hydrogeology and
      the distribution of atrazine, desethylatrazine, deisopropylatrazine,
      didealkylatrazine and hydroxyatrazine in runoff, pore water, and ground water.
      The data indicated that atrazine and its degradation compounds were transported
      from land surface to a depth of 1.5 m within 60 days of application, but were
      undetected in the saturated zone at nearby monitoring wells. A numerical model
      was developed, based on the field data, to provide information about processes
      that could retain and degrade atrazine in the vadose zone. Simulations indicated
      that evapotranspiration is responsible for surface directed soil-moisture flow
      during much of the growing season. This process causes retention and degradation
      of atrazine in the vadose zone. Increased residence time in the vadose zone leads
      to nearly complete transformation of atrazine and its degradation products to
      unquantified degradation compounds. As a result of macropore flow, small
      quantities of atrazine and its degradation compounds may reach the saturated
      zone.

PMID- 11286065
TI  - Evaluation of ground water monitoring network by principal component analysis.
AB  - Principal component analysis is a data reduction technique used to identify the
      important components or factors that explain most of the variance of a system.
      This technique was extended to evaluating a ground water monitoring network where
      the variables are monitoring wells. The objective was to identify monitoring
      wells that are important in predicting the dynamic variation in potentiometric
      head at a location. The technique is demonstrated through an application to the
      monitoring network of the Bangkok area. Principal component analysis was carried
      out for all the monitoring wells of the aquifer, and a ranking scheme based on
      the frequency of occurrence of a particular well as principal well was developed.
      The decision maker with budget constraints can now opt to monitor principal wells
      which can adequately capture the potentiometric head variation in the aquifer.
      This was evaluated by comparing the observed potentiometric head distribution
      using data from all available wells and wells selected using the ranking scheme
      as a guideline.

PMID- 11286066
TI  - Natural attenuation of volatile organic compounds (VOCs) in the leachate plume of
      a municipal landfill: using alkylbenzenes as process probes.
AB  - More than 70 individual VOCs were identified in the leachate plume of a closed
      municipal landfill. Concentrations were low when compared with data published for
      other landfills, and total VOCs accounted for less than 0.1% of the total
      dissolved organic carbon. The VOC concentrations in the core of the anoxic
      leachate plume are variable, but in all cases they were found to be near or below
      detection limits within 200 m of the landfill. In contrast to the VOCs, the
      distributions of chloride ion, a conservative tracer, and nonvolatile dissolved
      organic carbon, indicate little dilution over the same distance. Thus, natural
      attenuation processes are effectively limiting migration of the VOC plume. The
      distribution of C2-3-benzenes, paired on the basis of their octanol-water
      partition coefficients and Henry's law constants, were systematically evaluated
      to assess the relative importance of volatilization, sorption, and biodegradation
      as attenuation mechanisms. Based on our data, biodegradation appears to be the
      process primarily responsible for the observed attenuation of VOCs at this site.
      We believe that the alkylbenzenes are powerful process probes that can and should
      be exploited in studies of natural attenuation in contaminated ground water
      systems.

PMID- 11286067
TI  - Distribution functions of spring discharges according to their lithologies and
      the influence of lower limit to flow: an example from Spain.
AB  - Specific functions of distribution of the number of springs and of their
      contributions according to flow for each of nine lithological groups are
      established. These functions confirm the suitability of a general type of
      distribution (Sanz 1996), which is a borderline case of the lognormal
      distribution. The statistical methods proposed for the lithological types
      presented can be applied to any region if data on flow and lithology of the
      aquifers drained by springs are available. These methods have been applied to
      Spain, a representative region with varied geology, climate and topography; 71.2%
      of spring flow is supplied by limestones, 19.17% by alluvial sediments and marls,
      6.7% by conglomerates and sandstones, and 3% by slates, plutonic rocks,
      quartzites, and other groups. Springs with discharge rates exceeding 2000 L/s
      exist only in limestones. The majority of springs with low flow occur in marls.
      If we consider springs with flow greater than 0.5 L/s, alluvial sediments,
      sandstones, marls, and limestones have the greatest density of springs per
      surface area, although the average flow varies greatly from one lithology to the
      next. The cumulative estimated discharge and the estimated number of springs
      depend upon the definition of the lower limit of flow. For example, total
      discharge is reduced by 30% if we eliminate all springs with flow lower than 0.5
      L/min.

PMID- 11286068
TI  - Use of quantitative models to design microbial transport experiments in a sandy
      aquifer.
AB  - A suite of numerical models was applied to the problem of designing field tracer
      and bacterial injection experiments in a sandy surficial aquifer near Oyster,
      Virginia. The models were constructed based on the integration of diverse
      characterization data including hydrologic, geophysical, geological, geochemical,
      and biological information. A one-dimensional particle-tracking model was used to
      analyze laboratory transport experiments conducted using intact core samples to
      prescribe transport parameters describing solute dispersion and bacterial fate. A
      geostatistical model of three-dimensional hydraulic conductivity variations was
      developed, conditioned on in situ measurements of hydraulic conductivity and
      interpretations of geophysical data, and used to generate alternative aquifer
      descriptions. A regional-scale, two-dimensional flow model was used to design
      pumping rates of a forced-gradient hydraulic control system. Information from
      these various models was then combined into a high-resolution, three-dimensional
      flow and transport model for the prediction of field-scale solute and bacterial
      transport. Model predictions were used in an iterative experimental design
      process to specify: (1) the locations of multilevel samplers for monitoring
      transport; (2) frequency and timing of sample collection during bromide tracer
      injection experiments; and (3) frequency and timing of sample collection during a
      bacterial injection experiment. At each stage of the design, information gained
      during the previous stage was used to refine the model and target subsequent
      experimentation.

PMID- 11286069
TI  - Chemical erosion of the Lilburn Cave system, Kings Canyon National Park,
      California.
AB  - Multi-year instrumental records for input, throughflow and output waters of the
      Lilburn Cave system provide control on denudation rates as they respond to
      seasonal and spatial variability. Data suggest that maximum denudation is in the
      late fall and early winter. This is when non-snowmelt discharge is at its
      maximum. At lower discharge rates the volume of water moving through the cave
      system is the limiting control on the volume of denudation. During periods of
      snowmelt the limiting control is the rate at which the calcite dissolves. This is
      probably the result of water flowing through wider channels during these times.
      Based on instrumental measurements, there is considerable variation in terms of
      where denudation occurs inside the cave. The loci of dissolution change from year
      to year. This is to be expected in the dynamic environment of the cave where
      materials shift routinely. This variability should be studied over longer periods
      of time in order to more fully understand its extent. The relatively small area
      of carbonate exposure relative to the area of the drainage basin gives rise to
      relatively high denudation rates. The carbonate is being removed at a rate of
      about 5000 metric tons per year, or at about 830 mm/y. This is about five times
      the rate reported in the humid karst regions of Malaysia. This information
      indicates that the relative proportion of carbonate in the drainage basin needs
      to be considered when trying to estimate denudation in other areas.

PMID- 11286070
TI  - A rapid screening-level method to optimize location of infiltration ponds.
AB  - A rapid-screening technique was developed to identify lithologies that best
      disperse artificial recharge via surface infiltration and minimize effects on
      ground water chemistry. The technique prospectively evaluates basin infiltration
      rates and water chemistry influences by integrating geotechnical, hydraulic, and
      water quality data with column test data and numerical modeling. The technique
      was validated using field data collected from surface infiltration basins
      designed to recharge ground water pumped from the Pipeline pit gold mine in
      Nevada. Observed recharge rates at these infiltration sites correlated most
      significantly with depth to groundwater, with basins in coarse-grained
      lithologies performing better (0.45 to 0.85 m/day) than those with fine-grained
      layers (< 0.30 m/day). Observed water quality resulting from leaching of the
      previously unsaturated vadose zone showed a transitory (< six months) increase in
      solute concentrations followed by a decrease to baseline conditions, a phenomenon
      also observed in column tests that leached native soils with local ground water.
      Leaching of fine-grained soils with evaporites resulted in greater solute
      concentrations (TDS > 2000 mg/L) than coarse-grained soils (< 1200 mg/L). The
      results of HYDRUS_2D simulations using the accumulated data as input were in
      agreement with observed ground water chemistry downgradient of the infiltration
      basins for a variety of lithologies. Sites for infiltration basins can be rapidly
      screened to include areas with greatest depth to groundwater and in coarsest
      alluvial sediments, and impact to ground water chemistry can be reliably
      predicted using computer modeling and column test results.

PMID- 11286071
TI  - Sources of salinity in ground water from Jericho area, Jordan Valley.
AB  - One of the major problems in the lower Jordan Valley is the increasing
      salinization (i.e., chloride content) of local ground water. The high levels of
      salinity limit the utilization of ground water for both domestic and agriculture
      applications. This joint collaborative study evaluates the sources and mechanisms
      for salinization in the Jericho area. We employ diagnostic geochemical
      fingerprinting methods to trace the potential sources of the salinity in (1) the
      deep confined subaquifer system (K2) of Lower Cenomanian age; (2) the upper
      subaquifer system (K1) of Upper Cenomanian and Turonian ages; and (3) the shallow
      aquifer system (Q) of Plio-Pleistocene ages. The chemical composition of the
      saline ground water from the two Cenomanian subaquifers (K1 and K2) point to a
      single saline source with Na/Cl approximately 0.5 and Br/Cl approximately 7 x 10(
      3). This composition is similar to that of thermal hypersaline spring that are
      found along the western shore of the Dead Sea (e.g., En Gedi thermal spring). We
      suggest that the increasing salinity in both K1 and K2 subaquifers is derived
      from mixing with deep-seated brines that flow through the Rift fault system. The
      salinization rate depends on the discharge volume of the fresh meteoric water in
      the Cenomanian Aquifer. In contrast, the chemical composition of ground water
      from the Plio-Pleistocene Aquifer shows a wide range of Cl- (100-2000 mg/L),
      Na/Cl (0.4-1.0), Br/Cl (2-6 x 10(-3)), and SO4/Cl (0.01-0.4) ratios. These
      variations, together with the high SO4(2-), K+, and NO3- concentrations, suggest
      that the salinity in the shallow aquifer is derived from the combination of (1)
      upconing of deep brines as reflected by low Na/Cl and high Br/Cl ratios; (2)
      leaching of salts from the Lisan Formation within the Plio-Pleistocene Aquifer,
      as suggested by the high SO4(2-) concentrations; and (3) anthropogenic
      contamination of agriculture return flow and sewage effluents with distinctive
      high K+ (80 mg/L) and NO3- (80 mg/l) contents and low Br/Cl ratios (2 x 10(-3)).
      Our data demonstrates that the chemical composition of salinized ground water can
      be used to delineate the sources of salinity and hence to establish the
      conceptual model for explaining salinization processes.

PMID- 11286072
TI  - A strategy for modeling ground water rebound in abandoned deep mine systems.
AB  - Discharges of polluted water from abandoned mines are a major cause of
      degradation of water resources worldwide. Pollution arises after abandoned
      workings flood up to surface level, by the process termed ground water rebound.
      As flow in large, open mine voids is often turbulent, standard techniques for
      modeling ground water flow (which assume laminar flow) are inappropriate for
      predicting ground water rebound. More physically realistic models are therefore
      desirable, yet these are often expensive to apply to all but the smallest of
      systems. An overall strategy for ground water rebound modeling is proposed, with
      models of decreasing complexity applied as the temporal and spatial scales of the
      systems under analysis increase. For relatively modest systems (area < 200 km2),
      a physically based modeling approach has been developed, in which 3-D pipe
      networks (representing major mine roadways, etc.) are routed through a variably
      saturated, 3-D porous medium (representing the country rock). For systems
      extending more than 100 to 3000 km2, a semidistributed model (GRAM) has been
      developed, which conceptualizes extensively interconnected volumes of workings as
      ponds, which are connected to other ponds only at discrete overflow points, such
      as major inter-mine roadways, through which flow can be efficiently modeled using
      the Prandtl-Nikuradse pipe-flow formulation. At the very largest scales, simple
      water-balance calculations are probably as useful as any other approach, and a
      variety of proprietary codes may be used for the purpose.

PMID- 11286073
TI  - Assessing herbicide concentrations in the saturated and unsaturated zone of a
      Chalk aquifer in southern England.
AB  - The behavior of the herbicides isoproturon (IPU) and chlortoluron (CTU) in ground
      water and shallow unsaturated zone sediments were evaluated at a site situated on
      the Chalk in southern England. Concentrations of IPU in ground water samples
      varied from < 0.05 to 0.23 microgram/L over a five-year period of monitoring, and
      were found to correlate with application of the pesticide. Concentrations of
      pesticides in ground water samples collected during periods of rising water table
      were significantly higher than pumped samples and suggest that rapidly
      infiltrating recharge water contains higher herbicide concentrations than the
      native ground water. Significant variations in herbicide concentrations were
      observed over a three-month period in ground water samples collected by an
      automated system, with concentrations of IPU ranging from 0.1 to 0.5 microgram/L,
      and concentrations of a recent application of CTU ranging from 0.2 to 0.8
      microgram/L. Different extraction methods were used to assess pore water
      concentrations of herbicides in the unsaturated zone, and samples were analyzed
      by standard HPLC analysis and immunoassay (ELISA) methods. These data indicated
      highly variable concentrations of herbicide ranging from 4 to 200 g/ha for HPLC
      and 0.01 to 0.04 g/ha for ELISA, but indicate a general pattern of decreasing
      concentrations with depth. The results of this study indicate that transport of
      IPU and CTU through the unsaturated zone to shallow ground water occurs and that
      this transport increases immediately following herbicide application. Measured
      concentrations of herbicides are generally lower than specified by the European
      Union Drinking Water Directive, but are observed to spike above this limit. These
      results imply that, while delivery of pesticides to ground water can occur as a
      result of normal agricultural practices, the impact on potable supplies is likely
      to be negligible due to the potential for degradation during the relatively long
      travel time through the unsaturated zone and high degree of dilution that occurs
      within the aquifer. As a result of the wide variation in concentrations detected
      by different techniques, it is suggested that for future site investigations more
      than one sampling strategy be employed to characterize the occurrence of
      pesticide residues and elucidate the transport mechanisms.

PMID- 11286074
TI  - Extension of Vedernikov's graph for seepage from canals.
AB  - In this investigation, using previously derived equations by Vedernikov and Morel
      Seytoux, closed-form solutions have been obtained to compute the seepage from a
      slit and a strip. Also, a graphical solution as an extension of Vedernikov's
      graph has been presented for computing quantity of seepage from triangular,
      rectangular, and trapezoidal canals. The solution replaces approximately the
      cumbersome evaluation of improper integrals with unknown implicit transformation
      variables.

PMID- 11286075
TI  - Influence of transient flow on contaminant biodegradation.
AB  - The rate of biodegradation in contaminated aquifers depends to a large extent on
      dispersive mixing processes that are now generally accepted to result from
      spatial variations in the velocity field. It has been shown, however, that
      transient flow fields can also contribute to dispersive mixing. The influence of
      transient flow on biodegrading contaminants is particularly important since it
      can enhance mixing with electron acceptors, further promoting the reactive
      process. Using numerical simulations, the effect of transient flow on the
      behavior of a biodegradable contaminant is evaluated here both with respect to
      the development of apparently large horizontal transverse dispersion and also
      with respect to enhanced mixing between the substrate (electron donor) and
      electron acceptor. The numerical model BIO3D, which solves for advective
      dispersive transport coupled with Monod-type biodegradation of substrates in the
      presence of an electron acceptor, was used for the simulations. The model was
      applied in a two-dimensional plan view mode considering a single substrate.
      Transient flow fields were found to yield larger apparent transverse dispersion
      because the longitudinal dispersivity also acts transverse to the mean flow
      direction. In the reactive case, the transient flow field increases substrate
      oxygen mixing, which in turn enhances the overall rate of biodegradation. The
      results suggest that in the case of moderate changes of flow directions, a steady
      state flow field can be justified, thereby avoiding the higher computational
      costs of a fully transient simulation. The use of a higher transverse horizontal
      dispersivity in a steady flow field can, under these conditions, adequately
      forecast plume development.

PMID- 11286076
TI  - A stream depletion field experiment.
AB  - A field experiment was carried out to measure drawdowns in observation wells and
      stream depletion flows that occurred when water was abstracted from a well beside
      a stream. The field data is analyzed herein to determine the aquifer
      transmissivity, T, the aquifer storage coefficient, S, and a streambed leakage
      parameter, lambda, by comparing measurements with a solution obtained by Hunt
      (1999). The analysis uses early time drawdowns with a match-point method to
      determine T and S, and stream depletion measurements at later times are used to
      determine lambda. The final results are reasonably consistent for measurements
      taken in four observation wells. The advantages and disadvantages of this
      approach are discussed, and two alternative ways of estimating lambda are also
      discussed.

PMID- 11286077
TI  - Relating nitrogen sources and aquifer susceptibility to nitrate in shallow ground
      waters of the United States.
AB  - Characteristics of nitrogen loading and aquifer susceptibility to contamination
      were evaluated to determine their influence on contamination of shallow ground
      water by nitrate. A set of 13 explanatory variables was derived from these
      characteristics, and variables that have a significant influence were identified
      using logistic regression (LR). Multivariate LR models based on more than 900
      sampled wells predicted the probability of exceeding 4 mg/L of nitrate in ground
      water. The final LR model consists of the following variables: (1) nitrogen
      fertilizer loading (p-value = 0.012); (2) percent cropland-pasture (p < 0.001);
      (3) natural log of population density (p < 0.001); (4) percent well-drained soils
      (p = 0.002); (5) depth to the seasonally high water table (p = 0.001); and (6)
      presence or absence of a fracture zone within an aquifer (p = 0.002). Variables 1
      3 were compiled within circular, 500 m radius areas surrounding sampled wells,
      and variables 4-6 were compiled within larger areas representing targeted land
      use and aquifers of interest. Fitting criteria indicate that the full logistic
      regression model is highly significant (p < 0.001), compared with an intercept
      only model that contains none of the explanatory variables. A goodness-of-fit
      test indicates that the model fits the data well, and observed and predicted
      probabilities of exceeding 4 mg/L nitrate in ground water are strongly correlated
      (r2 = 0.971). Based on the multivariate LR model, vulnerability of ground water
      to contamination by nitrate depends not on any single factor but on the combined,
      simultaneous influence of factors representing nitrogen loading sources and
      aquifer susceptibility characteristics.

PMID- 11286078
TI  - A comparison of solute-transport solution techniques and their effect on
      sensitivity analysis and inverse modeling results.
AB  - Five common numerical techniques for solving the advection-dispersion equation
      (finite difference, predictor corrector, total variation diminishing, method of
      characteristics, and modified method of characteristics) were tested using
      simulations of a controlled conservative tracer-test experiment through a
      heterogeneous, two-dimensional sand tank. The experimental facility was
      constructed using discrete, randomly distributed, homogeneous blocks of five sand
      types. This experimental model provides an opportunity to compare the solution
      techniques: the heterogeneous hydraulic-conductivity distribution of known
      structure can be accurately represented by a numerical model, and detailed
      measurements can be compared with simulated concentrations and total flow through
      the tank. The present work uses this opportunity to investigate how three common
      types of results--simulated breakthrough curves, sensitivity analysis, and
      calibrated parameter values--change in this heterogeneous situation given the
      different methods of simulating solute transport. The breakthrough curves show
      that simulated peak concentrations, even at very fine grid spacings, varied
      between the techniques because of different amounts of numerical dispersion.
      Sensitivity-analysis results revealed: (1) a high correlation between hydraulic
      conductivity and porosity given the concentration and flow observations used, so
      that both could not be estimated; and (2) that the breakthrough curve data did
      not provide enough information to estimate individual values of dispersivity for
      the five sands. This study demonstrates that the choice of assigned dispersivity
      and the amount of numerical dispersion present in the solution technique
      influence estimated hydraulic conductivity values to a surprising degree.

PMID- 11286079
TI  - A modification to the Bouwer and Rice method of slug-test analysis for large
      diameter, hand-dug wells.
AB  - The Bouwer and Rice method of estimating the saturated hydraulic conductivity
      (Ks) from slug-test data was evaluated for geometries typical of hand-dug wells.
      A two-dimensional, radially symmetric and variably saturated, ground water
      transport model was used to simulate well recovery given a range of well and
      aquifer geometries and unsaturated soil properties, the latter in terms of the
      van Genuchten parameters. The standard Bouwer and Rice method, when applied to
      the modeled recharge rates, underestimated Ks by factors ranging from 1.3 to 5.6,
      depending on the well geometry and the soil type. The Bouwer and Rice analytical
      solution was modified to better explain the recovery rates as predicted by the
      numerical model, which revealed a significant dependence on the unsaturated soil
      for the shallow and wide geometries that are typical of traditional wells. The
      modification introduces a new parameter to the Bouwer and Rice analysis that is a
      measure of soil capillarity which improves the accuracy of Ks estimates by
      tenfold for the geometries tested.

PMID- 11286080
TI  - Stochastic-convective transport with nonlinear reactions and mixing: finite
      streamtube ensemble formulation for multicomponent reaction systems with intra
      streamtube dispersion.
AB  - An effective streamtube ensemble method is developed to upscale convective
      dispersive transport with multicomponent nonlinear reactions in steady nonuniform
      flow. The transport is cast in terms of a finite ensemble of independent discrete
      streamtubes that approximate convective transport along macroscopically averaged
      pathlines and dispersive transport longitudinally as microscopic mixing within
      streamtubes. The representation of fate and transport via a finite ensemble of
      effective linear streamtubes, allows the treatment of arbitrarily complex
      reaction systems involving both homogeneous and heterogeneous reactions, and
      longitudinal dispersive/diffusive mixing within streamtubes. This allows the use
      of reactive-transport codes designed to solve such problems in an Eulerian
      framework, as opposed to reliance on closed-form (convolutional or canonical)
      expressions for reactive transport in exclusively convective streamtubes. The
      approach requires both reactive-transport solutions for a representative ensemble
      of one-dimensional convective-dispersive-reactive streamtubes and the
      distribution of flux over the streamtube ensemble variants, and it does not allow
      for lateral mixing between streamtubes. Here, the only ensemble variant is travel
      time. The discussion details the way that the conventional Eulerian fate and
      transport model is converted first into an ensemble of transports along three
      dimensional streamtubes of unknown geometry, and then to approximate one
      dimensional streamtubes that are designed to honor the important global
      properties of the transport. Conditions under which such an 'equivalent' ensemble
      of one-dimensional streamtubes are described. The breakthrough curve of a
      nonreactive tracer in the ensemble is expressed as a combined Volterra-Fredholm
      integral equation, which serves as the basis for estimation of the distribution
      of flux over the variant of the ensemble, travel time. Transient convective speed
      and the effects of errors in flux distributions are described, and the method is
      applied to a demonstration problem involving nonlinear multicomponent reaction
      kinetics and strongly nonuniform flow.

PMID- 11286081
TI  - Analysis of field observations of tracer transport in a fractured till.
AB  - We analyze a set of observations from a recently published, field-scale tracer
      test in a fractured till. These observations demonstrate a dominant, underlying
      non-Fickian behavior, which cannot be quantified using traditional modeling
      approaches. We use a continuous time random walk (CTRW) approach which thoroughly
      accounts for the measurements, and which is based on a physical picture of
      contaminant motion that is consistent with the geometric and hydraulic
      characterization of the fractured formation. We also incorporate convolution
      techniques in the CTRW theory, to consider transport between different regions
      containing distinct heterogeneity patterns. These results enhance the possibility
      that limitations in predicting non-Fickian modes of contaminant migration can be
      overcome.

PMID- 11286082
TI  - Multicomponent simulation of wastewater-derived nitrogen and carbon in shallow
      unconfined aquifers. I. Model formulation and performance.
AB  - One of the most common methods to dispose of domestic wastewater involves the
      release of septic effluent from drains located in the unsaturated zone. Nitrogen
      from such systems is currently of concern because of nitrate contamination of
      drinking water supplies and eutrophication of coastal waters. The objectives of
      this study are to develop and assess the performance of a mechanistic flow and
      reactive transport model which couples the most relevant physical, geochemical
      and biochemical processes involved in wastewater plume evolution in sandy
      aquifers. The numerical model solves for variably saturated groundwater flow and
      reactive transport of multiple carbon- and nitrogen-containing species in a three
      dimensional porous medium. The reactive transport equations are solved using the
      Strang splitting method which is shown to be accurate for Monod and first- and
      second-order kinetic reactions, and two to four times more efficient than
      sequential iterative splitting. The reaction system is formulated as a fully
      kinetic chemistry problem, which allows for the use of several special-purpose
      ordinary differential equation (ODE) solvers. For reaction systems containing
      both fast and slow kinetic reactions, such as the combined nitrogen-carbon
      system, it is found that a specialized stiff explicit solver fails to obtain a
      solution. An implicit solver is more robust and its computational performance is
      improved by scaling of the fastest reaction rates. The model is used to simulate
      wastewater migration in a 1-m-long unsaturated column and the results show
      significant oxidation of dissolved organic carbon (DOC), the generation of
      nitrate by nitrification, and a slight decrease in pH.

PMID- 11286083
TI  - Multicomponent simulation of wastewater-derived nitrogen and carbon in shallow
      unconfined aquifers. II. Model application to a field site.
AB  - A multicomponent reactive transport model as presented by MacQuarrie and Sudicky
      [MacQuarrie, K.T.B., Sudicky, E.A., this volume. Multicomponent simulation of
      wastewater-derived nitrogen and carbon in shallow unconfined aquifers: I. Model
      formulation and performance, J. Contam. Hydrol.] is applied to a well-studied
      wastewater plume in a sandy aquifer near Cambridge, Ontario. Domestic wastewater
      is released into the unsaturated zone via a drain field at a depth of about 0.8
      m. The physical transport parameters for the model are obtained by simulating a
      non-reactive solute, while kinetic input data for the nitrogen and carbon
      reaction network are obtained from the literature. The model shows that the
      wastewater-loading rate has little influence on the moisture content in the
      unsaturated zone, thus oxygen diffusion in the air phase is an important
      transport mechanism. The model results are in general agreement with the field
      determined moisture and oxygen profiles near the drain field. The simulation
      results show that oxidation of ammonium and dissolved organic carbon (DOC) goes
      to completion in the 1.5-m distance between the drain field and the water table,
      and that calcite dissolution limits the pH reduction to about 0.2 units. The
      model-predicted nitrate concentrations in the core of the plume are in the range
      of 20-25 mg N/l and are in good agreement with the field data. Overall, the
      results for the major reactive species from the model simulation agree well with
      the geochemical data obtained below the drain field and it is concluded that the
      major physical and biochemical processes have been correctly captured in the
      current model formulation.

PMID- 11286084
TI  - [Bioaccumulation of elements and radionuclides by macrofungi. Review for
      territories of Poland].
AB  - A bibliographic review is presented on publications related to bioaccumulation of
      elements, specially metals and radionuclides in fruiting bodies of higher
      mushrooms collected at the territory of Poland. In the paper apart from the list
      of references in tables is given, chronologically, name of the first author, year
      of publication, site, the type of work (in situ, commercial source, field
      experiment, laboratory study), chemical symbols of the elements and the
      abbreviations of the latin names of the mushroom species under study.

PMID- 11286085
TI  - [Content of mercury in edible mushrooms on the terrains of Morag and Lukta].
AB  - Mercury concentrations were determined in the caps and stalks of seven species of
      edible mushrooms: Cantharellus cibarius, Xerocomus badius, Leccinum rufum,
      Leccinum scabrum, Boletus edulis, Tricholoma terreum and Marasmius oreades,
      collected at the area of the communes Morag and Lukta in the County of Ostroda in
      1997-98. The method of mercury measurement was cold-vapour atomic absorption
      spectroscopy (CV-AAS) after wet digestion of the samples with concentrated nitric
      acid under pressure in teflon vessels in microwave oven. There were a large
      variation of mercury content between examined mushrooms species. Boletus edulis
      showed a highest mercury concentration, i.e. 3.000 +/- 1.600 ng/g in the caps and
      1.800 +/- 900 ng/g dry matter in the stalks. The lowest mercury concentration was
      detected in Cantharellus cibarius and Tricholoma terreum.

PMID- 11286086
TI  - [Content of selected bioelements in complete daily food rations of students at
      the Bialystok Medical Academy].
AB  - The aim of the study was to evaluate calcium and iron content in a daily food
      ration of students of Bialystok Medical Academy. The analysis was correlated with
      the consumption of product groups being the main source of these bioelements in
      the diet (milk, meat and their products). The study involved 492 students (66%
      women and 34% men) aged 19-25 years. Quantitative analysis was carried out using
      the 24-hour recall method. Calcium and iron content in the diet were estimated
      according to Kunachowicz et al. The results were compared with the standards
      accepted by the Institute of Food and Nutrition in Warsaw, for people with
      moderate physical activity. The mean calcium content in the diet of female
      students was 582.9 mg, while in the diet of male students 802.2 mg. Daily diet
      calcium content covered 53% and 73% of the safe norm in women and men
      respectively, the recommended norm being 49% and 67%. Calcium content in a daily
      food ration of the Bialystok Medical Academy students was too low, which was
      caused by insufficient intake of milk and its products. Mean iron intake in a
      daily food ration of female students was 10.1 mg/day and of male students 15
      mg/day. The difference was statistically significant. Iron supply in men, s diet
      covered the recommended norm in 100%, while the safe norm in 136.4%. In women
      iron in diet covered the safe norm in 72.1% and the recommended norm in 56.1%.
      Differences in iron content in a daily food ration of the students examined are
      associated with differentiated consumption of meat and its products (high intake
      was noted in men studying at Bialystok Medical Academy).

PMID- 11286087
TI  - [Fatty acids in confectionery products].
AB  - The content of fat and fatty acids in 144 different confectionery products
      purchased on the market in Warsaw region during 1997-1999 have been investigated.
      In examined confectionery products considerable variability of both fat and fatty
      acids content have been found. The content of fat varied from 6.6% (coconut
      cookies) up to 40% (chocolate wafers). Saturated fatty acids were present in both
      cis and trans form. Especially trans fatty acids reach (above 50%) were fats
      extracted from nut wafers, coconuts wafers.

PMID- 11286088
TI  - [Evaluation of pharmacodynamic properties of medium-mineralized alkaline water
      designed for distribution as bottled natural mineral water].
AB  - Basing on the carried-out investigations it has been shown that the alkaline
      water from "Paproc" source in Tymbark indicates a biological activity. Applied in
      rats orally, in an appropriate dose through the period of 30 days, it causes a
      statistically significant increase of the pH of urine and blood, of the level of
      uric acid in urine and a statistic lowering of the levels of calcium and
      potassium in the blood serum. The investigated water shows diuretic activity,
      neutralizes and inhibits gastric juice secretion in people, affects the
      peristaltic movements of the smooth muscles of the small intestine of the rabbit.
      No effect of that water on the elements of the protein metabolism, the fat
      metabolism, on the smear and the morphological composition of the peripheral
      blood of rats, on the excretion of bile in guinea pigs has been observed.

PMID- 11286089
TI  - [Nutrition of preschool age children. General considerations and assessment of
      child nutrition].
AB  - Results of the study performed between June 1999 and January 2000 on dietary
      assessment of 822 pre-school children (age 3-7) showed that majority of children
      regularly consumed the main meals: breakfast, dinner and supper. The habit of
      snacks eating between the meals was observed in 91% of children. The presence and
      structure basic products in analysed children diets (milk, fermented milk
      products, fats, fish, whole grain bread, juices) was different. About 87%
      reported drinking of milk, 75%--yoghurt or other fermented milk products, 97%-
      fruit juices including nectar, water--42%. The main fat used to spreading on
      bread was butter. Fish products recommended as a source of n-3 polyunsaturated
      fatty acids were still not eaten by 23% of children. Whole grain bread was
      consumed daily only in 8% children. The study also showed that the diets included
      products being the source of unfavourable fatty acids (chips, sweet bars,
      cookies, hard margarine) and excess of saccharose (sweets, lollipops, chewing
      gum). The results of the study showed the permanent need of the dissemination of
      dietary recommendations for children at pre-school age.

PMID- 11286090
TI  - [Selected indices of nutritional status and food habits among young ballet
      dancers].
AB  - The work has been aimed at assessment of nutritional status on the base of some
      selected anthropometric factors and at evaluation of food habits among
      schoolchildren of the ballet dance school at Gdansk. The 58 boys and girls were
      examined. The height, body mass and body fat were measured, and the Body Mass
      Index values calculated. The results were compared to those obtained among
      children at Poznan and Kielce. The survey of food habits was made with the
      especially prepared questionnaire. The substantial deficiency of body fat and
      relatively low body mass were observed. The BMI value below 18 was found for 35%
      of subjects, and between 20 and 25 only for 23% of subjects. The wrong food
      habits were found, especially low number of meals and their irregular
      consumption.

PMID- 11286091
TI  - [Balance of magnesium and iron and their content in tissues and body fluids of
      rats after supplementation with magnesium carbonate].
AB  - Effect of magnesium on iron and magnesium metabolism in rats were investigated.
      96 male Wistar rats were divided into four groups received 2.5; 5.0 and 10.0 mg
      magnesium daily per kg of body weight--dissolved in 2%--solution of arabic gum
      (tests groups) or clear 2%--solution of arabic gum (test group) for 4 weeks and
      the next 4 weeks without supplements. Iron concentrations increased in the brain
      and kidney of the experimental rats, but decreased in the spleen, intestine and
      liver (2 and 4 weeks only) also in the heart and femur (only 8 week). Percentage
      of iron retention decreased during the whole experiment. Magnesium concentrations
      increased in the spleen, liver and intestine of rats. It was shown that at 8
      weeks of experiment the magnesium level of heart and femur decreased (only groups
      received 2.5 mg and 5.0 mg Mg/kg b.w./24 h), but in group received 10.0 mg Mg/kg
      b.w./24 h increased for all experiment. The apparent retention of magnesium
      increased in start of the experiment. This results show that oral magnesium
      supplementation disturbs metabolism of these elements, especially balance of
      iron.

PMID- 11286092
TI  - [The effect of selected tannery chemical compounds on selected bacteria of
      activated sludge].
AB  - Influence of tannery chemical compounds on the selected bacteria of the activated
      sludge was investigated. The chromium compounds must be diluted to 1:15-1:20 to
      loss its activity on the bacteria. Other compounds like: natrium chloratum,
      natrium formate and greased oils have any influence on the growth of the selected
      bacteria.

PMID- 11286093
TI  - Perceived outcomes of public health privatization: a national survey of local
      health department directors.
AB  - Almost three quarters of the nation's local health departments (LHDs) have
      privatized some services. About half of LHD directors who privatized services
      reported cost savings and half reported that privatization had facilitated their
      performance of the core public health functions. Expanded access to services was
      the most commonly reported positive outcome. Of those privatizing, over two
      fifths of LHDs reported a resulting increase in time devoted to management. Yet,
      one-third of directors reported difficulty monitoring and controlling services
      that have been contracted out. Communicable disease services was cited most often
      as a service that should not be privatized. There is a pervasive concern that by
      contracting out services, health departments can lose the capacity to respond to
      disease outbreaks and other crises.

PMID- 11286094
TI  - The managed care backlash: perceptions and rhetoric in health care policy and the
      potential for health care reform.
AB  - The focus on managed care and the managed care backlash divert attention from
      more important national health issues, such as insurance coverage and quality of
      care. The ongoing public debate often does not accurately convey the key issues
      or the relevant evidence. Important perceptions of reduced encounter time with
      physicians, limitations on physicians' ability to communicate options to
      patients, and blocked access to inpatient care, among others, are either
      incorrect or exaggerated. The public backlash reflects a lack of trust resulting
      from cost constraints, explicit rationing, and media coverage. Inevitable errors
      are now readily attributed to managed care practices and organizations. Some
      procedural consumer protections may help restore the eroding trust and refocus
      public discussion on more central issues.

PMID- 11286095
TI  - Improving the quality of workers' compensation health care delivery: the
      Washington State Occupational Health Services Project.
AB  - This article has summarized research and policy activities undertaken in
      Washington State over the past several years to identify the key problems that
      result in poor quality and excessive disability among injured workers, and the
      types of system and delivery changes that could best address these problems in
      order to improve the quality of occupational health care provided through the
      workers' compensation system. Our investigations have consistently pointed to the
      lack of coordination and integration of occupational health services as having
      major adverse effects on quality and health outcomes for workers' compensation.
      The Managed Care Pilot Project, a delivery system intervention, focused on making
      changes in how care is organized and delivered to injured workers. That project
      demonstrated robust improvements in disability reduction; however, worker
      satisfaction suffered. Our current quality improvement initiative, developed
      through the Occupational Health Services Project, synthesizes what was learned
      from the MCP and other pilot studies to make delivery system improvements. This
      initiative seeks to develop provider incentives and clinical management processes
      that will improve outcomes and reduce the burden of disability on injured
      workers. Fundamental to this approach are simultaneously preserving workers'
      right to choose their own physician and maintaining flexibility in the provision
      of individualized care based on clinical need and progress. The OHS project then
      will be a "real world" test to determine if aligning provider incentives and
      giving physicians the tools they need to optimize occupational health delivery
      can demonstrate sustainable reduction in disability and improvements in patient
      and employer satisfaction. Critical to the success of this initiative will be our
      ability to: (1) enhance the occupational health care management skills and
      expertise of physicians who treat injured workers by establishing community-based
      Centers of Occupational Health and Education; (2) design feasible methods of
      monitoring patient outcomes and satisfaction with the centers and with the
      providers working with them in order to assess their effectiveness and value; (3)
      establish incentives for improved outcomes and worker and employer satisfaction
      through formal agreements with the centers and providers; and (4) develop quality
      indicators for the three targeted conditions (low back sprain, carpal tunnel
      syndrome, and fractures) that serve as the basis for both quality improvement
      processes and performance-based contracting. What lessons or insights does our
      experience offer thus far? The primary lesson is the importance of making
      effective partnerships and collaborations. Our policy and research activities
      have benefited significantly from the positive relationship the DLI established
      with the practice community through the Washington State Medical and Chiropractic
      Associations and from the DLI's close association with the Healthcare
      Subcommittee of the Workers' Compensation Advisory Committee. This committee is
      established by state regulation and serves as a forum for dialogue between the
      committee and the employer and labor communities. Our experience thus underscores
      the importance of establishing broad-based support for delivery system
      innovations. Our research activities have also benefited from the close
      collaboration between DLI program staff and UW health services researchers. The
      DLI staff brought important program and policy experience, along with an
      appreciation of the context and environment within which the research, policy,
      and R&D activities were conducted. The UW research team brought scientific rigor
      and methodological expertise to the design and implementation of the research and
      policy activities. In Washington State, the DLI represents a "single payer" for
      the purposes of workers' compensation. As discussed earlier, Washington State,
      along with five other states, has a state-fund system that requires all employers
      that are not self-insured to purchase workers' compensation insurance through the
      state fund. No matter what one feels about the merits or drawbacks of a single
      payer system of health care financing, the fact is that such a system creates
      important opportunities for policy initiatives and for research and evaluation.
      Our ability to access population-based data on injured workers and to develop
      policy initiatives through innovation and pilot testing to assess whether
      proposed changes are really improvements has been critical. Understanding what
      works within the constraints and complexities of the system on a small scale is
      critical in order to bring forth policy and processes that will be of value
      systemwide. Finally, we note that general medical care faces many of the same
      quality-related problems and challenges as occupational health care. Medical care
      for chronic diseases, such as diabetes, is often fragmented and uncoordinated.
      (ABSTRACT TRUNCATED)

PMID- 11286096
TI  - Hospital restructuring and the work of registered nurses.
AB  - American hospitals have undergone three waves of organizational restructuring in
      the past two decades. These changes have had direct effects on a key set of
      employees--nurses. A review of the relevant literature to identify the ways in
      which hospital restructuring affects the work of registered nurses focuses on
      three important structural characteristics of nursing work: nurses' work roles,
      workload, and control of work. The review concludes that the impact of
      restructuring on each of the characteristics affects nurses' satisfaction with
      their work and may also affect the quality of patient care. While much of the
      policy debate around restructuring focuses on the extent to which reductions in
      nurse staffing levels affects quality of care, it is important to examine not
      only changes in nurse staffing levels, but changes in the work performed by
      registered nurses, as well.

PMID- 11286097
TI  - Capitation and risk adjustment in health care financing: an international
      progress report.
AB  - In every system of health care, capitation payments have become the accepted tool
      used by health care purchasers in much of the developed world to determine
      prospective budgets. The policy prescription of capitation is perceived to
      address both equity objectives (of great importance in publicly funded systems of
      health care) and efficiency objectives (the dominant concern in competitive
      insurance markets). An examination of the current state of the art in 20
      countries outside the United States in which health care capitation has been
      implemented confirms that capitation has assumed central importance within
      diverse systems of health care. In practice, however, the setting of capitation
      payments has been heavily constrained to date by poor data availability and
      unsatisfactory analytic methodology.

PMID- 11286098
TI  - CRM--clinical or crew resource management?

PMID- 11286099
TI  - The solicitor from heaven.

PMID- 11286100
TI  - Medical evidence in criminal prosecutions.

PMID- 11286101
TI  - Black sheep, scapegoats and lambs to the slaughter--some reflections on the work
      of a protection organisation.

PMID- 11286102
TI  - The legal liability, if any, of the company doctor to the prospective employee or
      other examinee.

PMID- 11286103
TI  - [Direct measurement of nitric oxide levels in aqueous humor with selective iso-NO
      electrode under physiologic conditions and after phacoemulsification and
      artificial acrylic lens implantation in experiments on rabbits].
AB  - PURPOSE: Using a direct method, with selective and nitric oxide sensitive
      electrode Iso-NO, we estimated the level of the Nitric Oxide (NO) in the aqueous
      humor of the rabbit's eye after phacoemulsification and acrylic foldable lens
      implantation. We also analysed the NO level during early postoperative days
      between the 1st and the 5th postoperative day. The current methods of the NO
      level estimations are also considered. MATERIAL AND METHODS: We examined 30 gray
      rabbits (weighing 3.0-3.5 kg). Just before surgery, samples of aqueous humor were
      aspirated. Lens was extracted with phacoemulsification technique. In 15 eyes
      acrylic foldable IOL was implanted and 15 eyes were left aphacic. The aqueous
      samples were collected 1, 3, 5 days after surgery. Nitric oxide in each sample
      was determined with direct, selective nitric oxide sensitive electrode Iso-NO.
      Because of changing values of the NO concentration and its characteristic course,
      we expressed the concentration of NO in aqueous humor using field-under-curve
      method to compare it with control group. The results of our examination are
      presented in the absolute values. RESULTS: During physiological conditions the
      mean value of the field under curve of the NO concentration was estimated as
      4987.29 +/- 895.89. After phacoemulsification with or without artificial lens
      implantation the level of the NO was higher as compared to the control group.
      After phacoemulsification and acrylic foldable lens implantation the highest
      level of NO was estimated on the 1st postoperative day as 6917.10 +/- 1199.72.
      During the examinations, the field under curve of NO concentration was estimated
      as 6246.63 +/- 327.02 and 5172.28 +/- 552.67 (on the 3rd and 5th days
      respectively). Only on the 1st and the 3rd postoperative day, the value of the
      field under curve of NO was significantly higher as compared with the control
      group. In contrast, after phacoemulsification without lens implantation the
      highest value of NO field under curve, was estimated on the 3rd postoperative
      days as 5801.44 +/- 344.45. During the examinations, the field under curve of NO
      concentration was estimated as 5115.30 +/- 796.11 and 4837.12 +/- 205.87 (on the
      1st and the 5th days, respectively). Moreover, it was the only one day of
      examination with significantly higher value of NO field under curve as compared
      with the control. CONCLUSION: We came to conclusion that the level of nitric
      oxide in aqueous humor after phacoemulsification with or without artificial lens
      implantation is higher than in control group. The highest value of the field
      under curve was estimated on the 1st postoperative day after phacoemulsification
      and acrylic foldable lens implantation and on the 3rd postoperative day after
      phacoemulsification without lens implantation.

PMID- 11286104
TI  - [Direct measurement of nitric oxide levels in aqueous humor with selective iso-NO
      electrode under physiologic conditions and after extracapsular cataract
      extraction and artificial lens implantation with PMMA in experiments with
      rabbits].
AB  - PURPOSE: To estimate the level of the nitric oxide (NO) within the aqueous humor
      of the rabbit eye after ECCE and PMMA artificial lens implantation using
      selective, nitric oxide sensitive electrode Iso-NO. We analysed the NO level
      during early postoperative period between the 1st and the 5th day. MATERIAL AND
      METHODS: We examined 30 gray rabbits (weighing 3.0-3.5 kg). Just before surgery,
      samples of aqueous humor were aspirated to control the NO level in physiological
      condition. Lens was extracted with ECCE (envelope) technique. In 15 eyes PMMA IOL
      were implanted and 15 eyes were left aphacic. The aqueous samples were also
      collected 1, 3, 5 days after surgery. Nitric oxide in each sample was estimated
      directly with selective, nitric oxide sensitive electrode Iso-NO. Changing values
      of the NO concentration during the examination were expressed using evaluation of
      field under curve in the absolute values. Such results were compared with control
      group. RESULTS: During physiological conditions the mean value of the field under
      curve of the NO concentration was estimated as 4987.29 +/- 895.89. After ECCE
      with or without PMMA artificial lens implantation the levels of the NO were
      higher as compared to the control group. After ECCE and PMMA artificial lens
      implantation the highest level of NO was estimated on the 3rd postoperative day
      (7978.98 +/- 949.77). During the examinations the fields under curve of NO
      concentration were estimated as 6626.30 +/- 1176.53 and 6288.19 +/- 604.90 (on
      the 1st and the 5th days, respectively). On all postoperative days, values of the
      field under curve of NO were significantly higher as compared to the control
      group. In contrast, after ECCE without lens implantation the highest value of NO
      field under curve, was estimated on the 1st postoperative day as 11727.83 +/-
      1032.44. During the examinations, the fields under curve of NO concentration were
      estimated as 9841.52 +/- 698.06 and 5446.96 +/- 568.47 (on the 3rd and the 5th
      postoperative days, respectively). Moreover, on all days of examination the value
      of NO fields under curve were significantly higher as compared to the control
      group. CONCLUSION: The level of nitric oxide in aqueous humor after ECCE with or
      without artificial lens implantation was higher than in the control group. The
      highest value of the field under curve was estimated on the 3rd postoperative day
      after ECCE and PMMA artificial lens implantation and on the 1st postoperative day
      after ECCE without lens implantation. The use of direct selective electrode Iso
      NO is a simple method of nitric oxide estimation in aqueous humor, but the
      interpretation of results seems to be very difficult. This method may be suitable
      for comparative estimations of NO during the experimental works.

PMID- 11286105
TI  - [Trans-scleral resection of the ciliary body and choroidal melanoma].
AB  - PURPOSE: To present our preliminary results of trans-scleral resection of ciliary
      body and choroidal melanoma. MATERIAL AND METHODS: 16 patients aged 20-73 years
      (mean 56 years) were treated from February 1999 to March 2000. There were 10
      patients with ciliary body tumors, 2 with choroidal tumors and in 4 patients the
      tumor involved ciliary body and choroid. The mean basal diameter of tumors was
      9.4 mm and the mean thickness was 7.2 mm. Trans-scleral resection was performed
      in all cases. Adjunctive radiotherapy using 106Ru plaques was applied in 7 cases.
      RESULTS: Histopathologically the diagnosis of melanoma was confirmed in all
      cases. In 10 cases there were spindle cell melanomas and in 6 mixed type. The
      intra-operative complications were vitreous hemorrhage in 3 patients, vitreous
      loss in three and both complications in one patient. Post-operative complications
      occurred in 3 cases of single instances each of retinal detachment, retinal edema
      and haemophthalmus. After surgery visual acuity did not change in 9 eyes,
      improved in 2 and deteriorated in 5 eyes. CONCLUSIONS: Our preliminary results
      confirm the opinion that trans-scleral resection could be a valuable method in
      the treatment of intraocular melanoma.

PMID- 11286106
TI  - [Trans-scleral resection of choroidal malignant melanoma].
AB  - PURPOSE OF THE STUDY: Case presentation of local transscleral resection of
      choroidal malignant melanoma. MATERIAL AND METHODS: A 45-year-old woman with
      enormous choroidal tumor not suitable for treatment with ruthenium plaque.
      Methods--microsurgical, local transscleral tumor resection with subsequent
      ruthenium plaque application performed in general hypotension. RESULTS: Non
      complicated tumor resection proved the possibility of eye preservation with final
      distant vision 0.5 and close vision 1.0/30.

PMID- 11286107
TI  - [Trabeculectomy as the initial procedure in primary congenital glaucoma].
AB  - PURPOSE: To estimate the effectiveness of trabeculectomy performed in buphthalmic
      eyes. MATERIAL AND METHODS: 42 eyes of 24 children, 14 boys and 10 girls. There
      were 18 children (32 eyes) operated on at the age from 7 days to 12 months (group
      I) and 6 patients (10 eyes) at the age from 3 to 7 years (group II) with primary
      congenital glaucoma. Corneal diameter ranged from 11.5 to 15 mm in infants, in 10
      eyes of 6 children elder than 2 years it was from 13 to 15 mm. The axial length
      of eyeballs was from 19 to 23.5 mm. Forty five trabeculectomies were performed,
      in 3 cases they were repeated two and six years after the first procedure. Follow
      up was from 1 year to 22 years, mean 82 months, 7 years of group I, 6 years of
      group II. RESULTS: 29 of 42 eyes (64.2%) with intraocular pressure varied between
      8 and 21 mm Hg, other eyes required additional local antiglaucoma treatment.
      Normal IOP was obtained in 95.2% of eyes. Trabeculectomy normalized IOP in 68.9%
      eyes of infants (group I), whereas in elder children the percentage came up to 50
      (group II). In other eyes pharmacological agents decreased IOL to values below 21
      mm Hg, in the group I in 97% of eyes and in the group II in 90% of cases.
      CONCLUSION: Trabeculectomy performed as a first procedure in primary congenital
      glaucoma is effective in infants and older children with buphthalmos in long-term
      follow-up. The necessity to perform this operation in very small children and
      even neonates does not always mean poor prognosis, and intraocular pressure can
      be stabilized at safe level for many years.

PMID- 11286108
TI  - [Structural changes in the cornea after LASIK-u during the early postoperative
      period].
AB  - PURPOSE: The study aimed to evaluate in vivo the corneal structure after
      refractive surgery and monitor morphologic and morphometric changes in the post
      operative period. MATERIAL AND METHODS: The study included 35 eyes (25 patients)
      who underwent LASIK correction of myopia. The structure of the cornea was
      evaluated in vivo using a scanning slit confocal microscope. Each cornea was
      examined before, 2, 4 and 8 weeks after procedure. The keratocyte density was
      evaluated morphometrically in the anterior and posterior corneal stroma. RESULTS:
      Before surgery the keratocyte density in the anterior stroma ranged from 900 to
      1200/mm2, while in the posterior stroma it ranged from 600 to 950/mm2. 8 weeks
      after LASIK the keratocyte density in anterior stroma ranged from 695 to 1048/mm2
      and in posterior stroma from 565 to 935/mm2. CONCLUSIONS: After LASIK the
      keratocyte density decreases in anterior stroma while in posterior stoma it is
      constant.

PMID- 11286109
TI  - [Changes in corneal structure observed with confocal microscopy during Fuchs
      endothelial dystrophy].
AB  - PURPOSE: The study aimed to in vivo evaluate corneal structure in Fuchs'
      dystrophy. MATERIAL AND METHODS: Forty-two eyes of 21 patients (11 women and 10
      men) aged 34-80 (mean 60.8) were studied. Sixteen patients presented clinical
      symptoms. The cornea was examined using a Confoscan P4 scanning slit confocal
      microscope (Tomey). Before examination, the cornea was anesthetized with 0.5%
      propacaine (Alcaine, Alcon) in order to inhibit the corneopalpebral reflex. A 40x
      microscope objective was covered with a drop of polyarylic acid gel (Vidisic,
      Mann Pharma) and then it was moved horizontally close to the patient's cornea and
      the examination was carried out. RESULTS: In the early stage of Fuchs dystrophy,
      slit biomicroscopy revealed fine dark spots within the corneal endothelium, while
      in the advanced stage the cornea had the appearance of beaten metal. On confocal
      microscopy, there were diffused hyporeflective areas in the early-stage disease.
      The endothelial cells located beyond these areas were pleomorphic and
      polymegathic. In the late stage we observed diffused hyporeflective areas
      surrounded by hyperreflective endothelial cells, which could not be analyzed
      separately. Within the corneal stroma, the collagen fibers were blurred and the
      background illumination was increased. In the posterior part of the stroma, dark
      bands were seen. The epithelium contained cystic structures (blisters). The
      membranes of the basal cells were thickened and the background illumination was
      increased. CONCLUSIONS: Confocal microscopy allows to diagnose Fuchs dystrophy
      and visualize endothelial cells within the swollen cornea.

PMID- 11286110
TI  - [Use of cyclophotocoagulation with diode laser in treatment of secondary glaucoma
      in children].
AB  - AIM OF THE PAPER: To evaluate the effectiveness of transscleral diode laser
      cyclophotocoagulation in treatment of secondary glaucoma in children. MATERIAL
      AND METHODS: 50 children (50 eyes) with secondary glaucoma (aphakic,
      posttraumatic, in Sturge-Weber syndrome and in aniridia) which was uncontrolled
      with medical and surgical therapy or the surgery had a high risk of postoperative
      complications. In all patients diode laser transscleral cyclophotocoagulation has
      been performed. RESULTS: After one month intraocular pressure was reduced (with
      or without medical treatment) below 23 mm Hg in 40% of patients and after 6
      months in 68% of patients. The worst results were observed in posttraumatic
      glaucoma. CONCLUSION: Diode laser transscleral cyclophotocoagulation is a safe
      and effective method of secondary glaucoma therapy in children uncontrolled with
      other methods of medical and surgical therapy or when the surgery has a high risk
      of postoperative complications.

PMID- 11286111
TI  - [Correction of myopia with LASIK--two year observation].
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of
      correction of moderate and high myopia as well as myopic astigmatism with LASIK.
      MATERIAL AND METHODS: 112 randomly selected eyes (79 patients) were analyzed
      after LASIK. In this group there were 55 women and 24 men aged 17 to 50 (mean
      34.9). The eyes were divided into two groups (the first: between -8.0 D to -14.75
      D; the second: between -15.0 D to -23.0 D). The follow-up time was 24 months. The
      effectiveness of this method was evaluated on the basis of the best visual acuity
      without correction after LASIK procedure compared to the best visual acuity with
      correction before LASIK. The course of the healing process, the state of cornea
      and subjective symptoms were also evaluated. RESULTS: One week after the
      operation (after LASIK) a statistically significant decrease of mean visual
      acuity was observed. In group I after 2 weeks the mean visual acuity was in the
      same range of values compared with the visual acuity before the operation. In the
      next period no statistically significant were observed differences. In group II
      after 2, 4, and 12 weeks the mean visual acuity was equalized in comparison with
      the mean visual acuity before correction. After 6, 12 and 24 months statistically
      significant improvement of visual acuity was observed. CONCLUSION: On the basis
      of our own observations we can say that LASIK is an effective and safe method of
      myopia and myopic astigmatism correction.

PMID- 11286113
TI  - [Use of keratoprosthesis type "champagne cork"--case report].
AB  - Kerathoprosthesis application is limited to strictly definite indications such
      as: after a severe corneal scald, after repeated graft rejections or temporarily
      just before the intricate eye operation to expose the posterior segment.
      Considerable progress in this province has been observed since PMMA were
      introduced. Recently a new successful method of "champagne cork"
      kerathoprosthesis, described firstly by Worst, has been reported. It is designed
      as a reverse cone and in comparison with other models provides significantly
      wider range of vision and simultaneuosly better visibility of fundus, which are
      the main advantages of this prosthesis. In our case this pattern of prosthesis
      was implanted in general anaesthesis and 24 hours after operation the visual
      acquity was 3/50. The insight into fundus was too blurred to assess fundus
      details. After 48 hours the haemorrhage to corpus vitreum appeared and after 3
      months without clot absorption the decision was made to extract it by pars plana
      vitrectomy. In local anaesthesis the operation was performed with 3 typical
      entrance incisions, and clots that formed non-transparent membrane on the cone
      together with involved corpus vitreum were removed. After 24 hours visual acquity
      was 5/50 and corpus vitreum and retina could be assessed through an anterior
      segment. It seems that this type of kerathoprosthesis should be widely
      recommended.

PMID- 11286112
TI  - [Treating retinopathy of prematurity with laser diode photocoagulation].
AB  - AIM: The purpose of the study was to assess the outcomes of the diode laser in
      the treatment of retinopathy of prematurity and to discuss the up-to-date
      possibilities of treating of active phase of this disease. MATERIAL AND METHODS:
      96 children (185 eyes) treated with diode laser retinal photocoagulation for
      active stage 3 of ROP in our department in years 1996-2000. RESULTS: Favorable
      structural outcome was observed in 83.8% of treated eyes. In the remaining eyes
      the disease progressed despite of the treatment and falciform retinal fold
      (5.4%), partial retinal detachment (6.5%) and total retinal detachment (4.3%)
      developed. No serious complications were observed after the treatment.
      CONCLUSIONS: Diode laser retinal photocoagulation is a safe and effective
      procedure for treating active stage 3 of retinopathy of prematurity. It has been
      especially useful for treatment of changes in zone 1 and 2 of the disease. Diode
      laser photocoagulation is now the preferred method of treating active stage 3 of
      ROP in our department.

PMID- 11286114
TI  - [A case of orbital foreign body in a 17-year old boy].
AB  - The authors describe a case of a 17-year-old boy who sustained orbital trauma. It
      is very interesting on account of the foreign body size, its location and
      successful treatment outcome.

PMID- 11286115
TI  - [Trichotillomania--case report].
AB  - This paper presents a case of trichotillomania involving the eyelids and
      eyebrows. This is a chronic illness that may be difficult to treat. The most
      common approach consists of pharmacotherapy and psychotherapy combination.
      Trichotillomania, classified in DSM IV as an impulse control disorder is
      characterized by an irresistible urge to pull hair, accompanied by a build up of
      tension and subsequent sense of relief. The mean age of onset is 8 years for
      males and 12 for females. Hair is pulled from a variety of sites, most frequently
      from the scalp but also eyelashes, eyebrows, beard, armpit and the pubic area.

PMID- 11286116
TI  - [New generation of excimer laser--Asclepion Meditec MEL 70 G-Scan].
AB  - The new Asclepion-Meditec MEL 70 G-Scan represents a breakthrough in surgical
      application of excimer laser. The laser uses the latest generation of flying spot
      system which utilizes a SafeScan algorithm (patent pending) to avoid corneal
      surface irregularities. The system utilizes a Gaussian beam profile. In cases
      where the cornea has regular surface, the conventional excimer laser PRK or LASIK
      method will provide good results. If the cornea shows an irregular surface shape,
      custom-tailored, topography-based ablation, which has been adapted to the corneal
      irregularity, should provide better results. Asclepion-Meditec have added a TSA
      (Tissue saving Algorithm) module to TOSCA (Topography Supported Customized
      Ablations) software for carrying out topography-guided corrections. This module
      automatically minimises the tissue removal when calculating the correction
      program. MEL 70 G-Scan allows to treat all forms of refractive errors, myopia and
      myopic astigmatism -24 D sph, -12 D cyl, hyperopia and hyperopic astigmatism +16
      D sph, +8 D cyl, mixtus and irregular astigmatism.

PMID- 11286117
TI  - Synergistic antiviral effect of PEG-asparaginase (ONCASPAR), with protease
      inhibitor alone and in combination with RT inhibitors against HIV-1 infected T
      cells: a model of HIV-1-induced T-cell lymphoma.
AB  - We evaluated the anti-HIV-1 activity of the T-cell-specific protein inhibitor PEG
      asparaginase (PEG-ASNase) in human HIV-1-infected T-cells. We further examined
      the drug synergism between PEG-ASNase and the protease inhibitor Saquinavir
      (SAQ), both alone and in combination with nucleoside analog reverse transcriptase
      inhibitors (NRTI). Our drug synergism studies served as a model for an HIV
      induced T-cell lymphoma. Phytohemagglutinin [PHA(+)] stimulated T-cells were
      infected with HIV-1 and then treated with one or more drugs 90 minutes from the
      viral exposure. To measure inhibition of viral replication, we examined HIV-1 RT
      and HIV-1 RNA in the supernatant and intracellularly on day 7 post-infection and
      drug treatment. Last, we examined the effect of administering drugs immediately
      after HIV-1 infection of T-cells to simulate treatment after an accidental
      exposure to the virus. PEG-ASNase, even when used alone, has anti-HIV-1 activity
      in PHA(+)-stimulated T-cells due to inhibition of protein synthesis. When the
      drug was used with SAQ, the combination was synergistic in inhibiting HIV-1 RT
      and RNA in the supernatant and intracellularly by 2.5 log10 in comparison with
      controls. PEG-ASNase and SAQ were even more effective in inhibiting HIV-1
      replication when combined with the NRTI inhibitors azidothymidine (AZT) and (-)
      beta-2',3'-dideoxy-3'-thiacytidine (3TC, lamivudine). The addition of
      ribonucleotide reductase inhibitor, 2-methyl-1H-isoindole-1,3-dione (MISID),
      further potentiated the antiviral effect of the regimen. HIV-1 RT and RNA
      analyses showed that the administration of the PEG-ASNase + SAQ drug combination
      immediately following exposure to HIV-1 completely inhibited the infection of T
      cells in our in vitro T-cell model. From these results we conclude that PEG
      ASNase is a valuable T-cell-specific protein inhibitor against HIV-1 infection,
      when used singly or in combination with a protease inhibitor, an RT inhibitor and
      an RR inhibitor. Since PEG-ASNase is a drug of choice for the treatment of T-cell
      lymphomas, a combination regimen containing PEG-ASNase could be very effective in
      the treatment of HIV-1-induced T-cell lymphoma and possibly AIDS. Future studies
      are needed in HIV-infected and/or HIV-induced T-cell lymphoma patients to
      investigate these findings.

PMID- 11286118
TI  - Detection of chemoresistance profile of cell lines K562, KB, GLC4 and HL60
      through characterisation of the hmdr1, mrp and lrp transcripts.
AB  - The current trend in innovative cancer therapy is moving towards targeting the
      genes of interest by means of oligonucleotides developed for therapeutic or
      diagnostic use. These new approaches are of particular interest in oncology, and
      it would therefore be extremely useful to characterise all the biological tools
      currently available in this field. The chemoresistance profiles of four human
      cancer cell lines were determined by identifying of the operating conditions
      needed to characterise the presence of hmdr1, mrp and lrp mRNA by gene
      amplification.

PMID- 11286119
TI  - A new rare allele at the CGG repeat polymorphism in the first intron of human c-H
      ras gene.
AB  - We have examined a region in the first intron of the human c-H-ras gene
      containing a CGG repeat. This region was previously shown to be variable in
      length. The length variation was attributed to the presence of the CGG repeat
      after estimation of its electrophoretic mobility. In the present report we have
      characterized in detail this region by PCR-RFLP and automated sequencing, in a
      total of 102 histologically normal tissues from unrelated individuals affected by
      lung and breast cancer. Four alleles were detected and analysis of their internal
      sequence showed that the length alterations of this region were due to the
      presence of 5, 6, 8 and 9 CGG triplets respectively. The last three occur most
      often (44.1%, 34.8%, 20.6% respectively) and coincide with three previously
      reported alleles (Riggins et al, Hum Mol Genet 9: 775, 1992). The fourth allele
      consisting of 5 repeats is a rare one (0.5%), whilst alleles with 7, and a
      previously reported one suggested to comprise 11 repeats (1%) were not present in
      our cohort. This polymorphism coincides in position with an element that was
      previously shown to possess regulatory activity.

PMID- 11286120
TI  - Chronic colitis in baboons: similarities with chronic colitis in humans.
AB  - In recent years, a substantial number of baboons died at the Southwest Foundation
      for Biomedical Research following protracted intractable diarrheas. The
      histopathologic diagnosis at autopsy was chronic colitis. The diarrhea could last
      for more than one year and occurred in infants, juveniles or young adult baboons,
      i.e. < or = 8 years of age (a healthy baboon may live up to 27 years). The aim
      was to assess the histopathologic subtype of chronic colitis in a relatively
      large number of colonic specimens obtained at autopsy (n = 132). In 88 out of 132
      baboons with chronic diarrhea, the colonic mucosa was well preserved for
      histological examination. At review, various histological phenotypes of chronic
      colitis were disclosed in 86 of the 88 baboons. Chronic lymphocytic-plasmacytic
      colitis was found in 54.6% (47 out of 86), chronic ulcerative colitis in 15.1%
      (13 out of 86), Crohn's colitis in 12.8% (11 out of 86), superficial lymphocytic
      colitis in 10.5% (9 out of 86), cryptal lymphocytic colitis in 5.8% (5 out of 86)
      and collagenous colitis in 1.2% (1 out of 86). Chronic ulcerative colitis,
      Crohn's colitis, superficial lymphocytic colitis and collagenous colitis in
      baboons closely mimic corresponding histological phenotypes of chronic colitis in
      humans. Recently, cryptal lymphocytic colitis has also been found in humans. The
      awareness that chronic colitis in baboons is not one disease but a series oi
      chronic inflammatory changes, having common clinical symptoms and similar gross
      appearance, may lead to the correct diagnosis of the subtype of the disease. Only
      then would it be feasible to systematically initiate the search for the
      corresponding etiologic agent(s), aiming to tailor specific therapeutic
      strategies in those animals.

PMID- 11286121
TI  - Insulin increases blood flow rate in the microvasculature of cremaster muscle of
      the anesthetized rats.
AB  - The hemodynamic actions of insulin in skeletal muscle microvasculature are not
      yet well elucidated. In the present study, we investigated the effects of
      systemic insulin injection on arteriole and capillary diameter and blood flow
      rate in rat cremaster muscle, using intravital real-time confocal laser-scanning
      microscope system in combination with selective fluorescent labeling.
      Subcutaneous insulin injecbon (1 U/kg) significantly increased serum insulin
      levels at 15 minutes as compared with saline injection. At 15 and 30 minutes
      after insulin injection, blood glucose levels were significantly lower compared
      to saline injected controls. Arteriolar diameter was significantly increased at
      15 and 30 minutes by insulin. Arteriolar erythrocyte flow velocity was
      significantly increased at 15 and 30 minutes. In addition, capillary erythrocyte
      flow velocity was increased at 15 and 30 minutes. These results demonstrated that
      calculated blood flow rates in capillary and arteriole increased after insulin
      injection.

PMID- 11286122
TI  - Changes in thymidine incorporation into tumor cells induced by supernatants of
      calcium-ionophore-treated macrophages incubated with tumor cells.
AB  - Thioglycollate-elicited peritoneal M phi of mice were treated with calcium
      ionophore A23187 prior to incubation with tumor cells. Supernatants prepared from
      the incubation mixtures were assayed for their effects on incorporation of 3H
      thymidine into tumor cells. Significant inhibition of incorporation was observed
      in most instances. Ingestion of indomethacin in the drinking water for 7 days by
      prospective M phi donors increased the inhibition by supernatants. The activity
      of the supernatants was neither specific for the strain and sex of M phi donors
      nor correlated with the genotype of the tumors. The activity even crossed the
      species barrier inasmuch as inhibitory supernatants were produced by murine M phi
      incubated with either murine or human tumor cells. Supernatants derived from
      murine as well as human tumor cells significantly depressed thymidine
      incorporation into murine and human tumor cells, although there were some
      differences in the response of the two kinds of tumor cells. In rare instances,
      supernatants enhanced, rather than inhibited, thymidine incorporation. Moreover,
      when supernatants, added to tumor cells, were removed and replaced by fresh
      medium, in most instances, significant enhancement of thymidine incorporated
      occurred. The formation of both growth-inhibiting and growth-promoting factors by
      M phi in the in vitro model used in this study, may explain the dual role of M
      phi in neoplasia in vivo.

PMID- 11286123
TI  - Diverse biological activities of healthy foods.
AB  - Diverse biological activities of 7 healthy foods [powdered pine needle, citrate
      fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame
      oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))]
      were investigated. The pine needle, sesame and powdered coffee was also extracted
      successively by ethanol and hot water, and lyophilized. The pine needle and
      coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and
      oxidation activity, as compared with other 4 lipophilic healthy foods. However,
      propolis showed slightly lower, but significant cytotoxic and bactericidal
      activity with much reduced oxidation potential. ESR spectroscopy demonstrated
      that the cytotoxic activity of these extracts was closely related to their
      radical generation and O2- scavenging activities. Healthy food components may
      have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with
      pine needle, sesame or powdered coffee extract significantly reduced the
      lethality of bacterial infection, possibly due to their host-mediated action.
      These extracts failed to reduce the cytophatic effect of HIV-1 (human
      immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was
      detected in mice by oral administration of 10 g/kg of these extracts. This data
      suggest the medicinal efficacy of healthy foods.

PMID- 11286124
TI  - Preventive effects of a Chinese herbal medicine, hochu-ekki-to, on bone loss in
      ovariectomized rats.
AB  - To evaluate the effects of a traditional Chinese herbal medicine, Hochu-ekki-to
      [Bu-zong-yi-qi-tang], on the bone loss induced by ovariectomy in rats,
      ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were
      daily given Hochu-ekki-to and/or 17 alpha-ethynylestradiol for 8 weeks by gastric
      tube and, subsequently, the serum hormone levels and the tibial bone mineral
      density were measured. Hochu-ekki-to treatment suppressed the ovariectomy-induced
      reduction of the bone mineral density in the whole and metaphysis of tibia with a
      slight increase of serum levels of estradiol and progesterone, maintaining bone
      mineral density values similar to that in the estradiol treated ovariectomized
      rats, as well as the intact control rats. Hochu-ekki-to is suggested to elevate
      the serum levels of ovarian hormones slightly and prevent bone loss in
      ovariectomized rats.

PMID- 11286125
TI  - Accumulated means analysis: a novel method to determine reliability of behavioral
      studies using continuous focal sampling.
AB  - During the past decade, the behavioral needs, and especially the social needs, of
      laboratory animals have received increasing attention. New captive care
      guidelines have been developed, and these advocate group housing of laboratory
      animals whenever possible and appropriate. Analyses of behavioral observations
      are commonly used to assess the effects of experimental manipulations on
      behavioral responses. In studies of animal welfare, stress levels and effects on
      well being can be measured in this manner. Collecting the proper amount of data
      both to allow statistical analyses and to optimize time investment in data
      collection is a practical concern in behavioral research. The aim of the present
      study was to develop a simple method to estimate how much behavioral data should
      be collected in order to achieve a preset level of reliability across
      observations. This paper examines the behavior of 12 rhesus monkeys (Macaca
      mulatta) housed in two small social groups. Each monkey was observed for a total
      of two hours in 10 minute observation periods spread over 12 days. Accumulated
      Means Analysis, in which the accumulated mean for a behavior across successive
      observation sessions must meet several criteria, is proposed as a method to
      assess reliability across observations, thereby providing information concerning
      the optimum number of observational data sessions that need to be collected. The
      data in this study indicate that this optimum number of observations varies with
      the behavior being measured and with the group observed, as does the value of the
      Accumulated Means Analysis technique. Six hours of observation of rhesus macaques
      may be sufficient to provide the type of simple, yet reliable time budget (for a
      specific window of time) needed by those managing groups of primates. Accumulated
      Means Analysis should be applicable to behavioral data collected during multiple
      time periods on other non-human primate species, both in captivity and in the
      field.

PMID- 11286126
TI  - Apoptotic colonic disease: a new entity in a primate.
AB  - A Macaca fascicularis died following chronic, intractable diarrheas. At autopsy,
      the entire colon was macroscopically red and swollen. At histology, the most
      conspicuous histologic finding was a marked accumulation of intraepithelial
      apoptotic granules in the lower one third of the epithelium of the colonic
      crypts. The cells in those crypts showed various degrees of swelling or
      necrobiosis. Since no other explanation was found at autopsy, it was concluded
      that the marked apoptosis with marked epithelial cell destruction was the cause
      of the colonic disease which apparently resulted in untreatable protracted
      diarrheas in this animal. The term apoptotic colonic disease is proposed for this
      previously unreported condition.

PMID- 11286127
TI  - Arginine modulated cyclosporine-induced immune suppression in rats transplanted
      with gastric cancer cells.
AB  - BACKGROUND: The incidence of cancer is significantly increased in kidney
      transplant patients receiving cyclosporine treatment. It has been reported that
      arginine can modify cyclosporine-induced nephrotoxicity in rats. Whether arginine
      interfered with cyclosporine-induced immune suppression in tumor transplant is
      not clear. MATERIALS AND METHODS: Male Wistar rats were inoculated subcutaneously
      with human gastric cancer SC-M1 cells and separated into 4 groups; control,
      cyclosporine, cyclosporine plus arginine and cyclosporine plus glycine groups.
      The growth of SC-M1 tumor was monitored on 4, 7, 10, 14 and 21 days after tumor
      implant. In another set of experiments, the rats were separated into control,
      cyclosporine, arginine and cyclosporine plus arginine groups. After treatment for
      one week, mononuclear cells were collected and stained with anti-rat CD3 antibody
      followed by flowcytometric analysis. On the other hand, splenocytes from each
      group of rats were stimulated with phyto-hemaglutinin (PHA) to determine their
      DNA synthesis by 3H-thymidine uptake assay. RESULTS: The SC-M1 tumors in the
      cyclosporine-treated rats were larger than that of the arginine plus cyclosporine
      group. Although SC-M1 tumors were eventually rejected in Wistar rats, the
      duration of detectable SC-M1 tumors in cyclosporine-treated rats was longer than
      that of rats treated with arginine plus cyclosporine. More infiltrating
      inflammatory cells were detected at an early stage of tumor rejection in rats
      treated with arginine plus cyclosporine than in cyclosporine-treated rats. In
      vitro analysis of PHA-stimulated splenocyte proliferation showed that arginine
      activated lymphocyte proliferation while cyclosporine inhibited lymphocyte
      proliferation. Arginine significantly interfered with cyclosporine-induced growth
      inhibition of PHA stimulated lymphocytes (p = 0.0039). CONCLUSION: Using a tumor
      transplant model, we have found that dietary supplements of arginine interfered
      with cyclosporine-induced immunosuppression in rats. The antagonistic effect
      between arginine and cyclosporine on immune suppression is worthy of further
      investigation in organ transplant patients.

PMID- 11286128
TI  - Prediction of accelerated Ca-induced Ca release rate by clinical findings in
      malignant hyperthermia susceptible subjects.
AB  - BACKGROUND: An abnormally accelerated Ca-induced Ca release (CICR) rate is known
      to be correlated with malignant hyperthermia susceptibility (MHS). OBJECTIVE: To
      analyze significant clinical findings concerning CICR rate and develop a computer
      program for its prediction in human MHS. PATIENTS AND METHOD: Using data from 146
      subjects who had received a muscle biopsy for the determination of CICR rate,
      because of their anesthesia-related MHS history, we analyzed 23 different
      clinical features. There were 71 subjects with an abnormally accelerated CICR
      rate and 75 with a normal rate. Accelerated CICR rate was used as the objective
      variable whilst clinical findings and ages were used as independent variables and
      control variables, respectively. A multiple logistic regression model was
      employed for the analyses and the most suitable formulae for prediction were
      determined for use in the development of a computer program. RESULTS: The
      following 8 clinical findings were determined to be the most significant: the
      presence of muscle rigidity, the most serious PaCO2 reading (mmHg), peak body
      temperature (degree C), body temperature rate of increase over 15 minutes (degree
      C/15 minutes), most serious arterial pH reading, administration of dantrolene,
      improvement of acidosis with dantrolene, and time elapsed to peak body
      temperature after administration of anesthetics (minutes). By ranking the subject
      ages into 14 groups, we were able to minimize the prediction error rate with each
      corresponding formula. The computer program developed for prediction whilst
      consisted of these formulae yielded a sensitivity of 80% and a specificity of
      86%. CONCLUSION: This method of prediction may contribute to the accurate
      prediction of CICR rate at the bedside. For clinical convenience, we will
      distribute the computer program upon request.

PMID- 11286130
TI  - Bcl-2 expression as an apoptotic index in non small cell lung carcinomas.
AB  - To evaluate the bcl-2 protein expression in non small cell lung carcinomas
      (NSCLC) as an index of apoptosis of these tumors, in fine needle aspiration
      biopsies (FNABs) of the lung, we studied thirty-eight cases of NSCLC (25
      bronchogenic adenocarcinomas and 13 squamous. carcinomas. Bcl-2 protein was used
      as the primary antibody (monoclonal, DAKO) by Alkaline-phosphatase method. Very
      light haematoxylin was performed as the counterstain. The results were compared
      and confirmed histologically. A cytoplasmatic expression of the bcl-2 protein was
      found in 72% (18 out of 15) of the bronchogenic adenocarcinomas while 61.54% (8
      out of 13) of squamous carcinomas showed bcl-2 expression. For the quantitative
      analysis of our results, we used the t-test and the difference between those two
      histologic types was regarded as statistically significant with p < 0.001.

PMID- 11286129
TI  - Isolation and characterization of a protein from Mendole (Spicara maena) eggs
      that binds to DNA and inhibits its replication as well as its acid precipitation.
AB  - Proteins that bind and protect nucleic acids from acid precipitation have been
      characterized from human and mouse plasma. In the present study, one protein from
      Mendole (Spicara maena) eggs was purified to homogeneity, by means of acetone
      fractionation and Sephadex G-100 gel filtration. The protein inhibited DNA
      replication, exerted by various DNA polymerases. Amino-acid sequence analysis in
      the amino terminus revealed a unique sequence. Its possible physiological role is
      discussed.

PMID- 11286131
TI  - Matrix metalloproteinase expression in malignant melanomas: tumor-extracellular
      matrix interactions in invasion and metastasis.
AB  - Structural changes in the extracellular matrix (ECM) are necessary for cell
      migration during tissue remodeling and tumor invasion. The matrix
      metalloproteinases (MMPs) and their inhibitors have been shown to be critical
      modulators of ECM composition and are, thus, crucial in neoplastic cell invasion
      and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in
      human malignant melanomas (MMs) employing an indirect alkaline phosphatase
      conjugated immunocytochemical technique. Evaluation of the results was based on
      (a) the percent of neoplastically transformed cells/surrounding stroma that
      reacted positively and (b) a measure of staining intensity [graded from A
      (highest) to D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence
      homology, but exhibit differences in cellular synthesis and inducibility by
      cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10
      was found in MMs, especially in the ECM adjacent to blood vessels. Positive
      immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90%
      of the neoplastically transformed cells (++++), and the staining intensity was
      also the strongest possible (A,B). Focal (+), high intensity (A,B) staining could
      be detected for MMP-2, -9, and -13. Thus, it seems that the stromelysins are
      involved in the generalized growth and expansion of the neoplastic cell mass,
      while MMP-2, -9 and -13 are involved in the neoangiogenic and focal clonal
      selection and expansion phenomena associated with in situ tumor progression,
      invasion of the microvasculature, and metastasis.

PMID- 11286132
TI  - Immunocytochemical detection of matrix metalloproteinase expression in prostate
      cancer.
AB  - Structural changes in the extracellular matrix (ECM) are necessary for cell
      migration during tissue remodeling and tumor invasion. The matrix
      metalloproteinases (MMPs) and their inhibitors have been shown to be critical
      modulators of ECM composition and are, thus, crucial in neoplastic cell invasion
      and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in
      human prostatic carcinomas employing an indirect alkaline phosphatase conjugated
      immunocytochemical technique. Evaluation of the results was based on (a) the
      percent of neoplastically transformed cells/surrounding stroma that reacted
      positively and (b) a measure of staining intensity [graded from A (highest) to
      D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but
      exhibit differences in cellular synthesis and inducibility by cytokines and
      growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in
      lung adenocarcinomas, especially in the ECM adjacent to blood vessels. Positive
      immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90%
      of the neoplastically transformed cells (++++), and the staining intensity was
      also the strongest possible (A,B). Focal (+), low to high intensity (C to A)
      staining could be detected for MMP-2, while no immunoreactivity was observed
      employing MoABs directed against MMP-9 and -13. Thus, it seems that the
      stromelysins are involved in the generalized growth and expansion of the
      neoplastic cell mass, while MMP-2 is involved in the neoangiogenic and focal
      clonal selection and expansion phenomena associated with in situ tumor
      progression, invasion of the microvasculature, and metastasis.

PMID- 11286133
TI  - Immunocytochemical detection of the expression of members of the matrix
      metalloproteinase family in adenocarcinomas of the pancreas.
AB  - Structural changes in the extracellular matrix (ECM) are necessary for cell
      migration during tissue remodeling and tumor invasion. The matrix
      metalloproteinases (MMPs) and their inhibitors have been shown to be critical
      modulators of ECM composition and are, thus, crucial in neoplastic cell invasion
      and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in
      human pancreatic adenocarcinomas employing an indirect alkaline phosphatase
      conjugated immunocytochemical technique. Evaluation of the results was based on
      (a) the percent of neoplastically transformed cells/surrounding stroma that
      reacted positively and (b) a measure of staining intensity [graded from A
      (highest) to D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence
      homology, but exhibit differences in cellular synthesis and inducibility by
      cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10
      was found in lung adenocarcinomas, especially in the ECM adjacent to blood
      vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM
      surrounding over 90% of the neoplastically transformed cells (++++), and the
      staining intensity was also the strongest possible (A,B). Focal (+), high
      intensity (A,B) staining could be detected for MMP-2 and -13, while no
      immunoreactivity was observed employing the anti-MMP-9 MoAB. Thus, it seems that
      the stromelysins are involved in the generalized growth and expansion of the
      neoplastic cell mass, while MMP-2 and -13 are involved in the neoangiogenic and
      focal clonal selection and expansion phenomena associated with in situ tumor
      progression, invasion of the microvasculature, and metastasis.

PMID- 11286134
TI  - Effect of poly ICLC treatment on hepatic oxidative stress and antioxidant defense
      indices in Plasmodium yoelii nigeriensis infected mice.
AB  - BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal
      malaria infection in Swiss albino mice. Reactive oxygen species (ROS) are
      important mediators of tissue injury during malaria infection. OBJECTIVE: To
      study the status of hepatic oxidative stress and antioxidant defense indices
      during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and poly ICLC
      treatment of normal and P. y. nigeriensis infected Swiss albino mice. METHODS:
      Mice were divided into four groups viz., 1. Normal mice, 2. Normal mice treated
      with poly ICLC (5 mg/kg body weight, i.p.), 3. P. y. nigeriensis infected mice
      and 4. P. y. nigeriensis infected mice treated with poly ICLC (5 mg/kg body
      weight, i.p.). RESULTS: P. y. nigeriensis infection caused a significant increase
      in hepatic oxidative stress indices viz., xanthine oxidase and lipid
      peroxidation. This was accompanied by a significant increase in antioxidant
      defense indices viz., reduced glutathione (GSH), glutathione reductase while
      superoxide dismutase and catalase showed a significant decrease with respect to
      normal mice. Poly ICLC treatment of P. y. nigeriensis infected mice did not cure
      blood parasitemia. However, poly ICLC treatment of normal and P. y. nigeriensis
      resulted in an increased generation of hepatic oxidative stress and an associated
      increase in the antioxidant defense indices. CONCLUSION: poly ICLC therapy alone
      is not sufficient to treat the malaria infection caused by multiple drug
      resistant strain of P. y. nigeriensis. Therefore there is a need to develop newer
      antimalarias which can act alone or in combination with traditional antimalarials
      to be effective against drug resistant malarial parasite.

PMID- 11286136
TI  - Deceleration of carcinogenic potential by adaptation with low dose gamma
      irradiation.
AB  - Animals that have been exposed to a very low dose of radiation are known to have
      many physiological benefits. Very low dose of ionizing radiation also induces
      mechanisms whereby cell or tissue become better fit to cope with subsequent
      exposures of high doses. This phenomenon of low dose radiation is termed
      'adaptive response'. This response has been reported to be true in many
      biological systems and confirmed by experiments on chromosomal and chromatid
      aberrations, micronucleus formation, sister chromatid exchange tests, DNA
      mutation and cell survival study and using many other biological end points,
      although there are quite a few exceptions. The adaptation induced by low doses of
      radiation has been attributed to the induction of an efficient chromosome break
      repair mechanism at molecular and biochemical level. It is also substantiated in
      whole animal systems. When mice are initially conditioned with very small
      adapting doses, incidence of a challenging dose induced thymic lymphoma is
      recorded, with delayed latency and reduced frequency. Similarly, appearance of a
      transplanted barcl-95 thymic tumor has been delayed when mice are preconditioned
      with a small dose of radiation. Appearance and development of a tumour following
      transplantation of in vitro irradiated barcl-95 tumour cells with a small dose of
      1 cGy are also delayed and volume of the tumour is reduced. Latency period of
      radiation-induced leukemia is modified by prior treatment with an adapting dose
      of radiation. Neoplastic transformation of several human cultured cells is also
      significantly decreased by prior low dose exposure of radiation compared to non
      exposed cells. These results indicate that an earlier exposure to a small dose of
      radiation also reduces the radiation-induced carcinogenesis. Various aspects of
      molecular mechanism underlying the radio-adaptation have been explained. However,
      the mechanism underlying the inhibition of carcinogenesis by low dose radiation
      is yet to be fully resolved.

PMID- 11286135
TI  - Increased Na(+)-dependent D-glucose transport in small intestine of retinyl
      palmitate treated rats.
AB  - The administration of retinyl palmitate (RP) to rats enhanced Na(+)-dependent D
      glucose transport in the small intestine. Effects of RP on Na(+)-dependent D
      glucose cotransporter (SGLT1) in rat small intestine were investigated in this
      study. RP was orally administered (1000 IU/kg/day) to rats for 3 days. The uptake
      of [3H]D-glucose into the brush-border membrane vesicles (BBMV) of the RP-treated
      rats, was 1.7-fold larger than that of the control rats. The western blot
      analysis of SGLT1 protein in BBMV indicated that the amount of SGLT1 was
      unaffected by the RP treatment. Scatchard analysis of phlorizin binding to both
      BBMV also showed that the dissociation constant (Kd) and number of phlorizin
      binding site (Bmax) were unchanged by the RP treatment. The fluidity of the brush
      border membrane (BBM) was examined by measuring the fluorescence anisotropy of
      BBM labeled with 1, 6-diphenyl-1, 3, 5-hexatriene (DPH). The membrane fluidity
      decreased in the RP-treated rats compared with that of the control rats. In
      conclusion, the RP treatment increased the glucose transport in BBMV. This
      enhancement of glucose transport is unlikely due to the change in the amount of
      SGLT1 protein in BBM. The decrease of the BBM fluidity may contribute to the
      enhancement of glucose transport in BBM of the RP-treated rats by changing the
      affinity of SGLT1 for glucose and/or the turnover rate of SGLT1.

PMID- 11286137
TI  - The interspecies sensitivity to transplacental effects of carcinogens.
AB  - Childhood cancer is a serious problem in oncology. Because the period of high
      sensitivity to environmental effects has been suggested to be early in life, it
      is thought that a variety of influences on pregnant mothers might result in the
      development of neoplasia in offspring. Environmental and genetic factors have
      been shown to play a significant role in modifying transplacental tumorigenesis.
      To better understand the possible mechanisms governing this phenomenon, an
      analysis of interspecies sensitivity to the transplacental effect of carcinogens,
      reviewed herein, should be of interest to many specialists in medicine and
      biology.

PMID- 11286138
TI  - New interferon alfa formulation licensed for treatment of hepatitis C.

PMID- 11286139
TI  - Bayer agrees to $14 million settlement over Medicaid pricing.

PMID- 11286141
TI  - Weaknesses cited in VA national formulary.

PMID- 11286140
TI  - Withdrawn drugs posed greater health risk for women than men, GAO says.

PMID- 11286142
TI  - Surveys debunk negative images of managed care.

PMID- 11286143
TI  - California power shortage brings new focus on conservation.

PMID- 11286144
TI  - Link between volume and health care outcomes studied.

PMID- 11286145
TI  - Nurturing [correction of Nuturing] relationships: an essential ingredient of
      leadership.
AB  - All pharmacists must develop the skills necessary to establish caring
      professional relationships with patients and colleagues. An absence of such
      relationships makes it difficult to compete for resources, motivate staff, or
      provide the best care to patients. Getting to know the people you spend so much
      of your life with is not only logical but enriching. Good leaders promote the
      growth of others and find--to their surprise--that they have grown along with
      them. Good leaders take pride in the accomplishments of staffers and residents
      who distinguish themselves in pharmacy, but they also smile at the pictures of
      their babies. Having recently turned 50, I begin to see the professional legacy I
      will leave behind, and it is my turn to embrace a sense of deep personal
      fulfillment. As leaders, we influence not only the lives of the people closest to
      us, but the lives of many we may never know. It must be an awesome realization
      for John Webb to know that, through his leadership and compassion, he has had a
      profound effect on pharmacy practiced by generations of pharmacists. Mr. Webb, it
      is for this reason and for the endearment you inspire in so many colleagues and
      friends that I am honored to be named this year's John Webb Visiting Professor in
      Hospital Pharmacy.

PMID- 11286146
TI  - Treatment of intermittent claudication with pentoxifylline and cilostazol.
AB  - The pathophysiology of intermittent claudication (IC) and the role of
      pentoxifylline and cilostazol for treating IC are discussed. IC, a result of
      inadequate blood flow to the musculature, is the primary symptom of occlusive
      peripheral vascular disease (PVD). Patients with IC often have a decreased
      quality of life because of mobility limitations. PVD is a sign of generalized
      atherosclerosis and increases the risk of cardiac morbidity and mortality.
      Smoking, hypertension, diabetes mellitus, and increasing age may hasten the
      progression of PVD. Strategies for treating IC are aimed at improving symptoms
      and reducing the progression of atherosclerosis and include risk-factor
      modification, exercise, and antiplatelet therapy. Cilostazol and pentoxifylline
      are the only two drugs with FDA-approved labeling for use in treating IC. Both
      drugs have been shown to increase pain-free walking time and total distance
      walked, although there is some conflicting evidence for pentoxifylline.
      Cilostazol and pentoxi-fylline are fairly well tolerated; the most common adverse
      effects involve the gastrointestinal tract and central nervous system. Inhibitors
      of cytochrome P-450 isoenzymes 3A4 and 2C19 should be used cautiously in patients
      taking cilostazol, and this drug is contraindicated in patients with congestive
      heart failure. Cilostazol is more costly than pentoxifylline. Initiation of
      therapy with either pentoxifylline or cilostazol may be reasonable if risk-factor
      modifications, lifestyle changes, and antiplatelet therapy are not effective. The
      mainstays of therapy for IC are risk-factor modification, exercise, and
      antiplatelet therapy. If these prove inadequate, treatment with pentoxifylline or
      cilostazol may be reasonable.

PMID- 11286147
TI  - Impact of a pharmacist on drug costs in a coronary care unit.
AB  - The impact of clinical pharmacy services on direct drug costs in a coronary care
      unit (CCU) was studied. An observational, nonrandomized study was conducted on
      all patients admitted to the CCU to evaluate the impact of clinical pharmacy
      services on direct drug costs. Clinical pharmacy services were introduced into
      the CCU in July 1998. Patient characteristics, mean drug costs per admission,
      mean drug category costs per admission, and total hospital costs per admission
      were determined for October 1997 to June 1998 (nonintervention period), July 1998
      to March 1999 (intervention period 1), and April 1999 to December 1999
      (intervention period 2). The Clini-Trend program was used to estimate the total
      reduction in drug costs associated with documented pharmacist interventions from
      January to December 1999. Mean patient age, sex, admitting diagnosis-related
      group, Medicare case-mix index, ventilator days, length of stay, and number of
      deaths did not differ significantly among the three study periods. Mean +/- S.D.
      drug costs per admission for the nonintervention period were $374.05 +/- $75.51.
      With the introduction of clinical pharmacy services, mean +/- S.D. drug costs per
      admission were $381.94 +/- $66.16 (p > 0.1 for intervention period 1 compared
      with the nonintervention period) and $233.74 +/- $84.16 (p = 0.002 for
      intervention period 2 compared with the nonintervention period). From January to
      December 1999, 4151 pharmacist interventions were documented. The estimated
      reduction in drug costs associated with the interventions totaled $372,384. A
      pharmacist's clinical services in the CCU allowed for significant estimated
      reductions in total drug costs.

PMID- 11286148
TI  - Visual compatibility of amiodarone hydrochloride injection with various
      intravenous drugs.
AB  - The Notes section welcomes the following types of contributions: (1) practical
      innovations or solutions to everyday practice problems, (2) substantial updates
      or elaborations on work previously published by the same authors, (3) important
      confirmations of research findings previously published by others, and (4) short
      research reports, including practice surveys, of modest scope or interest. Notes
      should be submitted with AJHP's manuscript checklist. The text should be concise,
      and the number of references, tables, and figures should be limited.

PMID- 11286149
TI  - Redesigning technician training to accommodate more students and enhance
      learning.
AB  - Management Case Studies describe approaches to real-life management problems in
      health systems. Each installment is a brief description of a problem and how it
      was dealt with. The cases are intended to help readers deal with similar
      experiences in their own work sites. Problem solving, not hypothesis testing, is
      emphasized. Successful resolution of the management issue is not a criterion for
      publication--important lessons can be learned from failures, too.

PMID- 11286150
TI  - Update on management of scleroderma.

PMID- 11286151
TI  - Clinical relevance of statins: instituting treatment early in acute coronary
      syndrome patients.
AB  - The efficacy of statins in lowering the total and low-density lipoprotein
      cholesterol and reducing the risk of cardiac events is now well established. The
      secondary prevention studies started treatment several months after the acute
      event. However, the greatest risk of recurrence is shortly after the index event.
      Recent evidence from small-scale clinical trials shows that standard doses of
      statins can be both safe and effective when given early after an acute coronary
      event, including early after thrombolytic therapy for myocardial infarction.
      Angiographic studies have shown beneficial effects of pravastatin on coronary
      stenosis when initiated after a coronary event. While none of these studies have
      been powered to demonstrate an effect on outcome, each has shown a reduction in
      major cardiovascular events. Two large observational studies have shown a
      reduction in 6- and 12-month risk-adjusted mortality among post-MI patients
      treated early with statins. Large-scale trials of all statins are now in progress
      to evaluate further the efficacy of early initiation of statin therapy in acute
      coronary syndromes. The largest of these is the Australian Pravastatin Acute
      Coronary Treatment (PACT) study, which will compare early outcomes in patients
      treated with pravastatin versus placebo prescribed within the first 24 h of an
      acute coronary event.

PMID- 11286152
TI  - Clinical relevance of statins: their role in secondary prevention.
AB  - Five large randomized clinical trials show the benefits of lipid lowering with
      statins on cardiac morbidity and mortality. Three of these were secondary
      prevention trials--the Long-term Intervention with Pravastatin in Ischemic
      Disease (LIPID) study, Cholesterol and Recurrent Events (CARE), and Scandinavian
      Simvastatin Survival Study (4S). The CARE and LIPID studies, performed with
      pravastatin, comprise populations that are representative of the majority of
      patients with coronary disease in that they included subjects with 'average'
      cholesterol levels. The 4S study, using simvastatin, comprised a patient
      population with elevated lipid levels. Pooled data from three trials, CARE,
      LIPID, and the West of Scotland Coronary Prevention Study (WOSCOPS), were
      examined in the Pravastatin Pooling Project (PPP). Individual patient data from
      these three event trials were pooled into a single database, permitting subgroup
      analyses and providing increased power. In the PPP, pravastatin-treated patients
      had significantly lower all-cause mortality (7.9, vs. 9.8% in those receiving
      placebo, a relative risk reduction of 20%). Pravastatin treatment was associated
      with a significant 24% reduction in CHD mortality and a nonsignificant difference
      in other vascular deaths (17%) and noncardiovascular deaths (12%). However, the
      reductions in absolute risk were much larger in those with a history of coronary
      heart disease than in those without. In the combined analysis of CARE and LIPID,
      there was also a uniform relative risk reduction in both men and women. In high
      risk groups such as diabetics, smokers, hypertensives, and the elderly, there
      were also significant risk reductions in clinical end points. Finally, in the 598
      participants, who had a stroke (90% of which were non-fatal), CARE and LIPID
      individually demonstrated reductions in non-fatal and total stroke. These data
      confirm that benefits of treatment in secondary prevention of coronary heart
      disease encompasses prevention of stroke as well as coronary heart disease
      events. The benefits are found in those who have had unstable angina as well as
      myocardial infarction. These findings strengthen even further the case for much
      more widespread use of statins in secondary prevention.

PMID- 11286153
TI  - Changing the practice of cardiovascular medicine.
AB  - Five large randomized trials of statins in primary and secondary prevention show
      the benefits of lipid-modifying therapy on cardiac morbidity and mortality.
      Evidence is beginning to accumulate showing that early and aggressive treatment
      of patients with acute coronary syndromes (acute myocardial infarction or
      unstable angina) can result in reduced mortality and morbidity and imparts a
      variety of mechanistic benefits. Nevertheless, recent surveys of coronary heart
      disease prevention in Europe and the US indicate that current evidence-based
      management of risk factors such as hypercholesterolemia is not uniformly
      employed. In fact, in Europe, only about a third of patients discharged from the
      hospital after an acute coronary syndrome are receiving prescriptions for
      statins. In US, more than a fourth of adults are eligible for treatment according
      to national guidelines but two thirds of them do not receive it. Among those
      treated, a considerable number do not reach their target levels. Therefore,
      strategies are needed to improve prescribing patterns among physicians and
      compliance among patients. It is essential that clinicians be aware of the
      evidence base supporting early and aggressive treatment of patients with acute
      coronary syndromes and that this is communicated to all clinicians involved in
      their care of patients with acute coronary syndromes.

PMID- 11286154
TI  - The treatment potential in preventive cardiology.
AB  - The Joint European Societies--European Society of Cardiology, European
      Atherosclerosis Society and European Society of Hypertension--1998
      recommendations on prevention of coronary heart disease (CHD) in clinical
      practice set priorities and goals. The top priority is patients with established
      CHD, or other atherosclerotic disease, because they are already under the care of
      cardiologists and are at high risk of further morbidity and mortality. The
      lifestyle goals are to stop smoking, make healthy food choices and be active
      physically. The risk factor goals are a BP < 140/90 mmHg, total cholesterol < 5.0
      mmol/l (190 mg/dl) and LDL-cholesterol < 3.0 mmol/l (115 mg/dl). The appropriate
      use of prophylactic drug therapies--aspirin, beta-blockers, ACE inhibitors, lipid
      modification therapies and anticoagulants--is also a recommended goal. The final
      goal is to screen relatives of patients with premature CHD (men < 55 years and
      women < 65 years). Surveys of clinical practice such as EUROASPIRE (European
      Action on Secondary Prevention) have shown risk can be further reduced in
      patients with established CHD because many are not achieving these lifestyle and
      risk factor goals. So there is considerable potential to raise the standard of
      preventive care for coronary patients through more effective lifestyle
      intervention and the use of drug therapies with proven efficacy. For the patient,
      this will mean a longer life with better quality.

PMID- 11286155
TI  - Mechanisms of acute coronary syndromes and the potential role of statins.
AB  - The conventional concepts of the pathogenesis of acute coronary syndromes are
      changing. High-risk lesions are not necessarily the angiographicaly 'tight'
      stenoses. Rather, vulnerable lesions are those that are unstable, with a large
      lipid core and a thin fibrous cap. Plaque instability is closely related to the
      development of inflammation within the intima and acute coronary syndromes result
      from rupture of a vulnerable atherosclerotic plaque. Stabilization of lesions by
      modification of structure and content, rather than simple improvement in the
      luminal diameter, provides a new therapeutic target. Stabilization may be
      accomplished through lifestyle changes and appropriate pharmacologic therapy. In
      the past few years, it has become evident that a major beneficial effect of
      statins is to induce plaque stability and regression. In fact, statins, in
      addition to lowering low-density lipoprotein cholesterol, have a variety of
      pleiotropic, or cholesterol-independent, effects that make them a particularly
      suitable choice in patients with acute coronary syndromes. Among these are
      improvements in endothelial function, smooth muscle cells, thrombus
      formation/platelet function, and inflammation.

PMID- 11286156
TI  - [The bridle procedure in treatment of foot deformity in children with slight
      cerebral spastic paralysis].
AB  - OBJECTIVE: To evaluate the effectiveness of the Bridle procedure in treatment of
      foot deformity in children with slight cerebral spastic paralysis. METHODS: From
      February 1993 to April 1999, 32 cases with 57 deformed feet, due to slight
      cerebral spastic paralysis, which included 20 males and 12 females, ranging from
      4 to 14 years old, were reported after 6 to 74 months' follow-up, averaging 38
      months. Bilateral feet were involved in 25 cases and unilateral feet involved in
      7 cases. The deformities in all feet, including 26 feet of acroceph-foot
      deformity in 15 cases, 13 equinovarus deformity in 8 cases and 18 scissors gait
      deformity in 9 cases, were treated by Bridle procedure, followed by temporal
      external fixation of long-leg plaster splint for 6 to 8 weeks. RESULTS: Clinical
      observation revealed complete and permanent correction of deformity in 48 out of
      all 57 feet (84.2%), reoccurrence of deformity in 7 feet (12.3%), and occurrence
      of valgus deformity in 2 feet (3.5%). No joint stiffness was observed.
      CONCLUSION: The Bridle procedure is an easily performed operation and effective
      in the treatment of foot deformity in children with slight cerebral spastic
      paralysis.

PMID- 11286157
TI  - [Comparison of three types of vaginoplasty].
AB  - OBJECTIVE: To select a satisfactory surgical approach in vaginoplasty with
      minimum injury and maximum effectiveness. METHODS: From January 1997 to December
      1998, 86 cases of congenital absence of vagina were treated by three types of
      vaginoplasty, using abdominal skin graft, fetal skin graft and vulvar-inguinal
      skin flap respectively. The duration of operation and hospitalization, the wound
      healing of donor site, as well as the moist sensation of the artificial vagina
      and the sexual life quality were compared among the three types of vaginoplasty.
      RESULTS: Compared with those by abdominal skin graft and vulvar-inguinal skin
      flaps, the vaginoplasty by fetal skin graft had the shortest surgical duration (P
      < 0.01); the duration of hospitalization with fetal skin grafting was shorter
      than that of abdominal skin grafting (P < 0.01) but almost the same as that of
      vulvar-inguinal skin transferring (P > 0.05). The fetal skin grafting had minimum
      injury. Moreover, artificial vagina by fetal skin grafting had the best moist
      sensation and the most satisfactory sexual life quality (P < 0.01). CONCLUSION:
      In view of the minimum injury and maximum mimic of nature vagina, the
      vaginoplasty by fetal skin graft is the most ideal approach among the three types
      of vaginoplasty investigated in this trial.

PMID- 11286158
TI  - [The influence of interleukin-1 on nerve growth factor secretion in newborn rat
      astrocytes in vitro].
AB  - OBJECTIVE: To study the nerve growth factor (NGF) expression and the influence of
      IL-1 alpha or IL-1 beta on NGF secretion in newborn rat astrocytes. METHODS:
      Astrocytes obtained from the brain cortex of newborn rats were cultured and
      purified, and they were divided into three groups, experimental, control and
      blank groups. IL-1 alpha or IL-1 beta were added into the experimental group with
      25, 50 and 100 U/ml, each group was cultured for 24, 48 or 72 hours, and then the
      NGF contents in cultured astrocytes suspension media were measured by a two-cite
      enzymelinked immunoserbent assay (ELISA). RESULTS: Astrocytes could secret NGF by
      themselves and each concentration of IL-1 alpha or IL-1 beta media at any testing
      time could enhance NGF secreting in newborn rat astrocytes in certain degrees.
      The effects of IL-1 beta were stronger than IL-1 alpha, the strongest effect in
      the unit time was observed in IL-1 beta with 50 U/ml for 24 hours. CONCLUSION:
      Astrocytes can express NGF, and IL-1 alpha or IL-1 beta can enhance the NGF
      expression in newborn rat astrocytes.

PMID- 11286159
TI  - [Reconstruction of tissue engineered vascular model in vitro].
AB  - OBJECTIVE: To explore the feasibility of reconstructing tissue engineered vessel
      in vitro. METHODS: Bovine endothelial cells were isolated from calf thoracic
      aorta by enzyme digestion methods and subcultured and purified. The endothelial
      cells of the 3rd to 7th passages were seeded into the inner surface of tubular
      scaffold material by polyglycolic acid(PGA) coated with cross-linked collagen,
      and cultured in vitro for 10 days using dynamic rotation culture technique.
      Scanning electron microscopy was used to analyse the morphological
      characteristics, and prostacyclin released by endothelial cells was measured by
      radioimmunoassay of 6-keto-prostaglandin F1 alpha. RESULTS: The VIII factor
      staining of cultured endothelial cells was positive. The endothelial cells
      adhered well on the inner surface of tubular scaffold material with confluent
      monolayer covering(91.2 +/- 1.5)%. The endothelialized model released
      prostacyclin at a rate of (4.6 +/- 0.5) micrograms/cm2.min. There was significant
      difference to control group (P < 0.05). CONCLUSION: The PGA coating with collagen
      is an ideal scaffold for endothelial cells, the coverage rate is increased
      through dynamic rotation culture technique. It will lay a good foundation for
      architecture of a laminated structure of tissue engineered vessel.

PMID- 11286160
TI  - [The influence of tissue engineered tendon on subgroup of T lymphocytes and its
      receptor in roman chickens].
AB  - OBJECTIVE: To investigate the influence of tissue engineered tendon on subgroup
      of T lymphocytes and its receptor in Roman chickens. METHODS: The flexor
      digitorum profundus of the third toes of right feet in 75 Roman chickens were
      resected and made 2.5 cm defects as experimental model. They were randomly
      divided into five groups according to five repair methods: no operation (group
      A), autograft (group B), fresh allograft (group C), polymer combined with
      allogenous tendon cells (group D), derived tendon materials combined with
      allogenous tendon cells (group E). The proliferation and transformation of
      lymphocytes and contribution of CD4+, CD8+, CD28 and T cell receptor (TCR) were
      detected to study the immune response. RESULTS: The CD4+, CD8+ and TCR of group D
      and E were increased slightly than that of group B after 7 days, while after 14
      days, those data decreased gradually and no significant difference between tissue
      engineered tendon and autografts (P > 0.05), and there was significant difference
      between fresh allograft and tissue engineered tendon (P < 0.05). Lymphocytes
      transformation induced by conA also showed no significant difference between
      tissue engineered tendon and autografts (P > 0.05). CONCLUSION: Tendon cells are
      hypoantigen cells, there are less secretion of soluble antigen or antigen chips
      dropped out from cells. Tissue engineered tendon has excellent biocompatibility.

PMID- 11286161
TI  - [Transplantation of cultured human keratinocyte on collagen sponge].
AB  - OBJECTIVE: To investigate the skin regeneration using cultured human
      keratinocytes with collagen sponge transplanted into thickness wound of nude
      mice. METHODS: Human foreskin from foreskin ectomy procedures was detached with
      0.5% Dispase II. Epidermis sheets were separated from dermis and digested with
      0.05% Trypsin into single cell suspension. Keratinocytes were cultured and seeded
      into collagen sponge during logarithmic growth phase. After 3 days, the
      keratinocytes-collagen sponge were grafted on full thickness wound of nude mice,
      compared with simple collagen sponge without keratinocytes. The histological,
      immunohistochemical examination and electron microscopy were detected. RESULTS:
      After the epidermal substitute was grafted onto wound, the human keratinocytes
      were able to further proliferate and differentiate and develop into new
      epithelia. Compared with the control group, the wound healed earlier and
      contracted less, epithelia matured earlier, and the collagen fiber was less
      beneath epithelia. CONCLUSION: Keratinocytes can grow on collagen sponge and
      migrate onto wound to develop into stratified epithelia and inhibit wound
      contract. The keratinocyte graft can be used to repair skin defect.

PMID- 11286162
TI  - [Progress on evaluation criterion of wound healing].
AB  - OBJECTIVE: To set up some objective and accurate criteria to evaluate wound
      healing. METHODS: Documents about wound healing were reviewed and summarized in
      detail. RESULTS: Wound healing rate, wound healing time, histopathology analysis,
      quantity assay of macrophage, determination of hydroxyproline, proliferation of
      cell, assay of DNA contents and circle of cells, level of transforming growth
      factor-alpha, levels of interleukin-1, interleukin-6 and tumor necrosis factor,
      assay of keratinocyte collagenase-1, level of fibroblast growth factor receptor
      1, level of monocyte chemoattractant protein-1 and level of keratinocyte
      plasminogen activator inhabitor type 2 were selected as the evaluation criteria
      of wound healing. CONCLUSION: Wound healing rate, wound healing time and
      histopathology analysis are direct and efficient criteria of wound healing.

PMID- 11286163
TI  - [Effects of different methods of fetal spinal cord tissue transplanted on
      reversing the axotomy-induced neurons atrophy rats injured spinal cord].
AB  - OBJECTIVE: To explore the effects of different methods of fetal spinal cord(FSC)
      tissue transplanted on reversing the axotomy-induced neurons atrophy of adult
      rats injured spinal cord. METHODS: One hundred and twenty adult rats received
      lumbar spinal cord hemisection. Experimental rats were divided into five groups,
      the control group(Group A); spinal cord hemisection only(Group B); spinal cord
      hemisection plus FSC transplant (Group C); spinal cord hemisection plus FSC
      transplant plus pedicled paraspinal muscle(Group D); spinal cord hemisection plus
      FSC transplant plus pedicled omentum (Group E). Combined behavioral scores(CBS),
      somatosensory evoked potentials (SEP), motor evoked potentials(MEP) were examined
      to evaluate the recovery of neurological function after operation. Rats were
      sacrificed after 1, 4 and 12 weeks. Nissl stained section was used for neurons
      quantitative image analysis. The positive cells were quantitative analysis by
      computer image analysis system. RESULTS: The different methods of FSC tissue
      transplantation could prevent the neurons atrophy secondary to axon injury of
      spinal cord in adult rats. The size of neurons were observed in five groups, they
      were group E > group D > group C > group B > group A (P < 0.05). Those increases
      in size of neurons were paralleled with a significant improvement in neurological
      function recovery. CONCLUSION: It indicates that the different methods of FSC
      tissue transplantation can maintain the neurons morphology and improve the
      neurological function of rats.

PMID- 11286164
TI  - [Experimental study on combining selective rhizotomy of different anterior and
      posterior sacral roots for restoration of bladder function after spinal cord
      injury].
AB  - OBJECTIVE: To investigate an alternative procedure for complete denervation of
      bladder in the supra-cone cord injury to restore the bladder function. METHODS:
      Sixteen dogs were included in this study after their spinal cords were transected
      above the cone. They were divided into 6 groups and performed the rhizotomy of L7
      to S3 root in different combination respectively. The bladder and urethra
      pressure change by electrostimulation during operation and cystometrogram change
      after operation were tested. RESULTS: 1. Electrostimulation study: for bladder
      innervation, S2 was the most important and S1 was secondary. While for urethra
      innervation, S1 was more important than S2. When the anterior and posterior roots
      of S1 and S2 were intact with rhizotomy of posterior roots of L7 and S3,
      stimulated the common or posterior root of S1 and S2, the change of pressure in
      bladder and urethra was the same. When the anterior roots of S1 and S2 were
      resected with rhizotomy of posterior roots of L7 and S3, the pressure in bladder
      and urethra was significant decreased compared to stimulating the corresponding
      posterior roots. 2. Cystometrogram (CMG) study: in the complete deafferented
      group, resecting the posterior roots of L7 to S3, the bladder became flaccid.
      While resecting the posterior root of S2 and anterior root of S1 or, resecting
      the posterior root of S1 and anterior root of S2, combining with rhizotomy of
      posterior roots of L7 and S3, the CMG curve was similar to the complete
      deafferented group. In the S1 and S2 intact group, the bladder became spastic.
      CONCLUSION: Combining rhizotomy of anterior and posterior sacral root in
      different level has the same effects on bladder as complete deafferentation.

PMID- 11286165
TI  - [Effect of fetal spinal cord graft with nerve growth factor and nimodipine in
      secondary injury of spinal cord of adult rat].
AB  - OBJECTIVE: To observe the effect of nerve growth factor (NGF) and nimodipine (NP)
      on fetal spinal cord graft in repair of injury of spinal cord. METHODS: A total
      of 144 adult Wistar rats were included in this study. All were made as the hemi
      section cavity injury model at the lumbar enlargement and divided into three
      groups: fetal spinal cord graft (group Tr), fetal spinal cord graft with NGF
      (group TN), and fetal spinal cord graft with NGF and NP (group TNN). The
      intracellular concentration of free ionic calcium was measured at the 4th, 8th,
      and 24th hour, and superoxidase (SOD) and malondialdehyde (MDA) at 3rd, 6th,
      12th, 24th and 72nd hour after operation. RESULTS: After spinal cord was injured,
      the concentration of MDA and intracellular concentration of free ionic calcium
      increased and reached to the peak at the 6th and 8th hour respectively, but SOD
      decreased and at 24th hour to its vale. The MDA was significantly lower in group
      TN than in group Tr, while the SOD was higher (P < 0.05). There was no
      significant difference on intracellular free ionic calcium concentration between
      group Tr and TN. The concentration of SOD of group TNN was the highest and the
      intracellular concentration of free ionic calcium was the lowest in the three
      groups (P < 0.05). The weekly mortality was 33%, 31%, 17% respectively in group
      Tr, TN and TNN. The mortality of group TNN was significantly lower than the other
      two groups (P < 0.01). CONCLUSION: Although the fetal spinal cord graft is an
      effective method to repair laboratory spinal cord injury, NGF and ND can
      interrupt secondary injury and increase survival rate of the host.

PMID- 11286166
TI  - [Variation of neurotrophic factors expression in spinal cord and muscle after
      root avulsion of brachial plexus].
AB  - OBJECTIVE: To investigate the variation of neurotrophic factors expression in
      spinal cord and muscle after root avulsion of brachial plexus. METHODS: Forty
      eight Wistar rats were involved in this study and according to the observing time
      in 1st day, 1st week, 4th week, 8th week, and 12th week after avulsion, and the
      control, were divided into 6 groups. By immunohistochemical and hybridization in
      situ assays, the expression of nerve growth factor (NGF) on muscle, basic
      fibroblast growth factor(bFGF) and its mRNA on the neurons of corresponding
      spinal cord was detected. Computer image analysis system was used to calculate
      the result. RESULTS: After the root avulsion of brachial plexus occurred,
      expression of NGF increased and reached to the peak at the 1st day. It subsided
      subsequently but was still higher than normal control until the 12th week. While
      expression of bFGF and its mRNA increased in the neurons of spinal cord and
      reached to the peak at the 1st week. Then it dropped down and at the 12th week it
      turned lower than normal control. CONCLUSION: After root avulsion of brachial
      plexus, neurotrophic factors expression increase on target muscle and neurons of
      corresponding spinal cord. It maybe the autoregulation and may protect neuron and
      improve nerve regeneration.

PMID- 11286167
TI  - [Experimental study on closing the firearm injured soft tissue defect by skin
      stretch].
AB  - OBJECTIVE: To investigate the availability and effect of skin stretch in closing
      the firearm injured soft tissue defect. METHODS: Eight white pigs with firearm
      injured soft tissue defect were divided into 3 groups. Each group I and group II
      had 3 pigs which were performed skin stretch. The control group had 2 pigs
      without stretch. The average diameter of the defect in three groups was (7.3 +/-
      0.2) cm, (9.1 +/- 0.3) cm, (7.3 +/- 0.2) cm respectively, and the site of defect
      was on the lateral thigh and buttock. RESULTS: Skin stretch could make a visible
      reduction of the wound. It was possible to close the wound by direct traction
      when the diameter of the buttock wound was less than 7 cm, and when the diameter
      of the lateral thigh wound was less than the radius of thigh. The skin stretch
      should not last more than 7 days and the best effect appeared in 4 to 5 days
      after performing the skin stretch. CONCLUSION: The skin stretch can be applied in
      the repair of the firearm injured soft tissue defect. It has many advantage
      compared with the tradtional treatment.

PMID- 11286168
TI  - [Applied anatomy of the sensate latissimus dorsal muscular flap with the lateral
      posterior branch of the intercostal nerve].
AB  - OBJECTIVE: To provide anatomy basis for a free latissimus dorsal muscular flap
      with the sensate nerve. METHODS: The structure of back and lateral chest area
      were dissected and the origin, alignment and distribution of the intercostals
      nerve within the area of latissimus dorsal muscular flap were observed in 40
      adult cadaver specimens. RESULTS: The 5th to 10th lateral posterior branches of
      the thoracic nerve pierced from respective intercostal area near the axial
      anterior line and run a long distance in deep fascia. They distributed mainly in
      lateral latissimus skin outside the scapular line and anastomosed with the lower
      branch near the scapular line. Among these branchs, the 6th to 8th branches had a
      longer nerve distribution respectively and the pedicle of nerve and artery was
      parallel and long. CONCLUSION: It is possible to design a sensate latissimus
      dorsal muscular flap with the 6th to 8th lateral posterior branch of the
      intercostal nerve.

PMID- 11286169
TI  - [Anatomy and clinical application of vascularized tarsal bone flaps].
AB  - OBJECTIVE: To provide a series of surgical approaches for treatment of talus neck
      fracture, ischemic necrosis of talus body, and other bone lesions in ankle and
      foot. METHODS: The major blood supply to cuboid bone, medial cuneiform bone and
      navicular bone was observed in 30 adult cadavers, by infiltration of red emulsion
      via major arteries of the lower limbs. Based on these anatomical investigations,
      3 types of vascularized tarsal bone grafting were designed for repair of bone
      lesions in the area of ankle and foot, and applied in 49 clinical cases, ranging
      from 10 to 58 years in age, and 43 cases of which were followed up for 4 years
      and 3 months in average. RESULTS: Primary healing was achieved in 40 cases, and
      secondary healing achieved after further surgical intervention in other 3 cases.
      The function of all ankle joints recovered satisfactorily. CONCLUSION: The
      designed three types of vascularized tarsal bone flaps are easy and reliable for
      dissection because of their superficial pedicles, and they are available for
      different clinical cases with various bone lesions in ankle and foot.

PMID- 11286170
TI  - [Experimental study of allogenic tendon with sheath grafting in chicken].
AB  - OBJECTIVE: To investigate availability of deep freeze stored allogenic tendon
      with sheath grafting in repairing the tendon and sheath defect in the II area of
      flexor digitorum tendon. METHODS: Sixty chickens with tendon and sheath defect
      were divided into 2 groups randomly, group A was treated with allogenic grafting
      and group B was treated with autogenic grafting, these two groups were divided
      into two subgroups respectively, they were, group A1 allogenic tendon with whole
      sheath grafting, group A2 allogenic tendon with partial sheath grafting, group B1
      autogenic tendon with whole sheath grafting and group B2 autogenic tendon with
      whole sheath grafting. All the allogenic grafts were treated by deep freeze.
      Histomorphological study, histoimmunological study and slipping function of the
      grafts were measured after operation. RESULTS: In group A1 and B1, the local
      reaction was sever, the nutrition of tendon graft was barricaded by the whole
      sheath resulting in adhesion, degeneration and necrosis. In group A2 and B2, the
      tendon graft healed well and little adhesion existed between tendon and sheath.
      The results showed that there were significant differences between tendon
      grafting with whole sheath and tendon grafting with partial sheath. CONCLUSION:
      Deep freeze store can reduce the immunogenicity of allogenic tendon with sheath.
      Allogenic tendon with partial sheath grafting can be used as a new biological
      material for repairing the tendon and sheath defect.

PMID- 11286171
TI  - [Repair and functional reconstruction of severe electrical burns of wrist].
AB  - OBJECTIVE: To reduce amputation rate of severe electrical burn of wrist and to
      promote partial recovery of the injuried hand. METHODS: From 1987 to 1999, 44
      cases, with 55 limbs of severe electrical burn were classified into 4 types,
      according to criteria of Dr Shen Zuyao, and were all treated by primary adequate
      decompression, timely debridement, reconstruction of blood circulation in cases
      complicated with blood vessel injury, and skin flap grafting from chest, abdomen
      or inguinal area, followed by treatment of anti-coaggluation and anti-infection.
      Once the wound healed, auto- or allo-transplantation or transferring of tendons
      were performed to repair tendon defect, and auto-nerve or fetal nerve
      transplantation performed for nerve defect. RESULTS: After the primary treatment
      of the 55 burned limbs, all limbs of type IV were amputated, and most of other 3
      types survived. The function, including sensation and movement, of survived hands
      partially recovered. CONCLUSION: Primary reconstruction of blood circulation,
      cover of wound with skin flap, and timely repair of sensation and motor function
      are very crucial approach to reduce amputation rate and to promote the survived
      hand function of severe electrical burns of wrists.

PMID- 11286172
TI  - [Treating cicatricial baldness with scalp expanding and hair autografting].
AB  - OBJECTIVE: To investigate the effective method to treat cicatricial baldness.
      METHODS: From 1993 to 1998, 21 cases with multi-region or great-dimensional
      cicatricial baldness were treated with scalp expanding and hair autografting.
      Among them, there were 17 males and 4 females, aged from 14 to 49 years old. The
      operation was divided into two stages, stage one meaned to embed the expander
      under the scalp and stage two meaned to sow the autogenous hair. RESULTS: All
      cases, no matter what the position and area, were repaired successfully. The
      biggest dimension of repaired baldness was 340 cm2, one expander exposed and one
      failed in expanding after operation and be corrected immediately. The normal hair
      direction changed in two cases. CONCLUSION: Combined use of scalp expanding and
      hair autografting is an effective method to treat multi-region or great
      dimensional cicarticial baldness.

PMID- 11286173
TI  - [Interspecies lysogenization in staphylococci: transfer of bacteriophage
      converting enterotoxin A from a clinical strain of Staphylococcus aureus to
      Staphylococcus intermedius].
AB  - The ability of lysogenization was examined of 50 S. intermedius strains and of 77
      strains belonging to 14 different species of coagulase-negative staphylococci
      using 8 enterotoxin A converting bacteriophages isolated from S. aureus. All the
      examined bacteriophages showed lytic activity against at least 1 of 11
      susceptible strains of S. intermedius to them. Lytic activity towards coagulase
      negative staphylococci was observed for 6 of 8 examined bacteriophages. Two
      bacteriophages were active against 1 of 9 examined S. capitis strains, one
      against 1 of 11 examined S. haemolyticus strains, four against 1 of 6 examined S.
      lugdunensis strains, three against 1 of 6 examined S. warneri strains and one
      against 1 of 5 examined S. xylosus strains. Lysogenization with bacteriophage
      f421-1 able to convert positively enterotoxin A and staphylokinase and negatively
      beta-haemolysin of one S. intermedius strain was successful. S. intermedius
      lysogenized with phi 421-1 was able to produce both enterotoxin A and
      staphylokinase and lost ability to produce beta-haemolysin. Our results showed a
      broad lytic spectrum and interspecies host range of some S. aureus bacteriophages
      and the ability of interspecies transfer of bacteriophages between S. aureus and
      S. intermedius.

PMID- 11286174
TI  - [Evaluation of methicillin-resistance in Staphylococcus aureus by the agar disk
      diffusion method and PCR].
AB  - Staphylococcus aureus is a widespread human pathogen. One the most striking
      characteritics of this bacterium is resistance to methicillin and all beta-lactam
      antibiotics. The agar disk diffusion method is the most widely used in vitro
      susceptibility test, but recently molecular methods, e.g. Polymerase Chain
      Reaction, have been also introduced. We compared the detection of methicillin
      resistant coagulase positive Staphylococcus aureus isolated from clinical
      materials in Silesian microbiological laboratories by diffusion method and PCR
      through the detection of nuc and mec A genes. Our results show that PCR used for
      the detection of mec A gene increases the detection of methicillin-resistant
      Staphylococcus aureus strains by 10% as compared to the agar disk diffusion
      method. Among Staphylococcus aureus strains, detected as methicillin-resistant,
      17% of organisms showed no presence of mec A gene.

PMID- 11286175
TI  - [Changes of methicillin-resistant Staphylococcus aureus (MRSA) phagotypes in
      Gdansk in 1990-1998].
AB  - The aim of the study was the assessment of changes in the occurrence of various
      MRSA phagotypes in hospitals in the Gdansk area in 1990-1998. The study was
      carried out on 175 MRSA strains: 45 strains isolated in 1990-1995 and 130 in 1997
      1998. The studied staphylococci were obtained from various clinical materials
      from patients in 18 hospitals. Phagotyping was done with a set of 10 experimental
      phages from MRSA strains obtained from the Central Public Health Laboratory in
      London. Drug-resistance was determined by the disc-diffusion method and in case
      of strains with medium susceptibility to fusidic acid the minimal inhibitory
      concentration (MIC) was determined by serial dilutions on solid medium. The study
      showed among MRSA strains isolated in 1997-1998 a new, previously not known
      strains with phage pattern MR25/M5 predominated (57.7%). Its presence was found
      in various hospitals in that area. MRSA belonging to MR25/M5 phagotype were
      mostly resistant to doxycycline, gentamycin, erythromycin, clindamycin,
      ciprofloxacin, rifampicin and were resistant or only had medium susceptibility to
      fusidic acid. The MIC values for strains with medium susceptibility to fusidic
      acid (4-8 micrograms/ml) showed an evident decrease of the susceptibility to this
      antibiotic, formerly common in MRSA. At the same time, in 1997-1998 a
      considerable decrease was observed of the number of MRSA strains belonging to
      MR8/MR12/MR25/30/33/38/M5/622 phagotype (from 31.1% to 0.8%), and disappearance
      of strains with phagotypes MR25/56B/M3 and MR8/MR25/622, which in 1990-1995
      accounted for 15.6% of the studied staphylococci.

PMID- 11286176
TI  - [Susceptibility to selected coagulase-negative chemotherapeutic agents of
      methicillin resistant staphylococci isolated from clinical materials in 1997
      1998].
AB  - The study was aimed at assessment of the sensitivity of methicillin-resistant
      coagulase-negative staphylococci isolated from clinical material in 1997/1998 to
      selected chemotherapeutic agents. The investigated material comprised 96
      methicillin-resistant coagulase-negative staphylococci from hospital and
      ambulatory infections isolated during the period from April 1997 to May 1998.
      Species affiliation was determined by classical identification methods and
      commercial diagnostic tests for identification of staphylococci. Methicillin
      resistance was determined by agar disk-diffusion method and screening.
      Sensitivity to chemotherapeutics was determined by agar disk-diffusion method and
      agar dilution methods. All the investigated strains were sensitive to
      nitrofurantoin, furazolidone and vancomycin. To teicoplanin--the second
      glycopeptide antibiotic--84% strains were sensitive, whereas the percentages of
      resistant and moderately sensitive strains amounted to 5.2% and 10.4%,
      respectively. 85% and 82% of coagulase-negative staphylococcal strains were
      sensitive to fusidic acid and mupirocin. Considerable differences were noted with
      respect to sensitivity to aminoglycoside group antibiotics. About 35% of strains
      were sensitive to gentamicin, and 90% sensitive to netilmicin. Ca. 40% of
      coagulase-negative staphylococci were resistant both to cotrimoxazole and
      trimethoprim, which, in view of 98% resistance to the second component of
      cotrimoxazole, may be associated with the activity of only one of the components
      of the drug--trimethoprim.

PMID- 11286177
TI  - [Production of reactive nitrogen and oxygen intermediates in human granulocytes
      and monocytes during internalization of live BCG bacilli].
AB  - The production of nitric oxide (NO) and reactive oxygen intermediates in
      granulocytes and macrophages from healthy volunteers, infected in vitro with live
      Bacille Calmette-Guerin (BCG) mycobacteria, was estimated. Significant
      differences in the biochemical reactions induced by BCG bacilli in granulocytes
      and monocytes are described. The activity of phagocytes was also investigated in
      the cultures with cytokines: IFN-gamma, TNF-alpha, GM-CSF, IL-4.

PMID- 11286178
TI  - [Adhesion of human T lymphocytes and granulocytes to endothelial cells stimulated
      by cell-surface antigens of Bacteroides thetaiotaomicron].
AB  - The aim of this study was to assay the degree of human T lymphocyte and
      granulocyte adhesion to the vascular endothelial cells stimulated by Bacteroides
      thetaiotaomicron lipopolysaccharides, components of LPS and capsular
      polysaccharide. HMEC-1 cells were activated with bacterial preparations in
      concentration 10 micrograms/ml for 4 and 24 hours. T lymphocytes and granulocytes
      were isolated from peripheral blood of healthy blood donors. Thereafter, the
      adhesion tests of granulocytes and adhesion tests of non-activated and activated
      with PMA (in concentration 10 ng/ml) T lymphocytes to the resting and stimulated
      vascular endothelium were performed. The number of viable cells, which adhered to
      the endothelium, was determined using inverted microscope (magnification 200x).
      The results were presented as the number of viable cells adhering to 1 mm2 of the
      endothelial cell culture. The obtained results indicate that granulocytes and T
      lymphocytes (resting and activated with PMA) adhere to the endothelial cells
      stimulated by B. thetaiotaomicron cell-surface antigens. B. thetaiotaomicron
      lipopolysaccharides and capsular polysaccharide are weaker stimulants of human
      leukocyte adhesion to the HMEC-1 cells than E. coli O55:B5 LPS.

PMID- 11286179
TI  - [Intestinal flora of patients with suspected antibiotic associated diarrhea
      (AAD). I. Clostridium perfringens].
AB  - Stool samples of 158 patients suspected of antibiotic-associated diarrhoea (AAD)
      were studied. Toxin A of C. difficile and enterotoxin of C. perfringens were
      detected in stool samples by immunoenzymatic assays and PCR. In 35 stool samples
      toxin A of C. difficile was detected and in 48 cases (30%) C. difficile strains
      were cultured from 21 stool samples (13%). The presence of the cpe gene of C.
      perfringens, enabling the production of enterotoxin, could not be detected by
      PCR, both in stool samples and in isolated strains, using ent 1 and ent 2 primer
      pairs. C. difficile and C. perfringens were isolated from the same stool samples
      in 4 cases. From stool samples of two patients with AAD C. perfringens strains,
      thermoresistant spores were cultured.

PMID- 11286180
TI  - [Survival of Bacillus anthracis spores in various tannery baths].
AB  - The influence of tannery baths: liming, deliming, bating, pickling, tanning,
      retannage on the survival and on the germination dynamism of B. anthracis spores
      (Sterne strain) was investigated. The periods and the conditions of this
      influence were established according to technological process of cow hide
      tannage. Practically after every bath some part of the spores remained vital. The
      most effective killing of spores occurred after pickling, liming and deliming.
      Inversely, the most viable spores remained after bating and retannage process.
      The lack of correlation that was observed between survival and germination of
      spores after retannage bath can be explained by different mechanism of spores
      germination inhibition and their killing.

PMID- 11286181
TI  - [The influence of anaerobic bacteria and mycoplasma isolated from the genital
      tract on mast cell activation].
AB  - Nowadays, it is known that mast cells, numerously appearing in all organs and
      being a source of a wide range of mediators and cytokines, are involved both in
      physiological and pathological processes. The aim of our study was to examine
      whether vaginal bacteria, especially those participating in Bacterial vaginosis,
      are able to activate mast cells to mediators secretion. The study was done on rat
      peritoneal mast cells. The mast cells were incubated in vitro with suspensions of
      Bacteroides capillosus, Actinomyces naeslundii (2 strains), Peptostreptococcus
      spp., Lactobacillus fermentum (2 strains), Mycoplasma hominis or Ureaplasma
      urealyticum killed by temperature. Activation of mast cells was estimated on the
      basis of histamine release. It was established that M. hominis, U. urealyticum
      and B. capillosus strongly stimulated rat mast cells to histamine secretion
      (histamine release 53.0%, 17.4% and 10.0%, respectively). Histamine release
      induced by Peptostreptococcus spp., A. naeslundii and L. fermentum was lower (at
      a range of 2.4%-8.2%). The obtained results can suggest that presumably
      interactions between vaginal bacteria and placental mast cells could influence
      the course of pregnancy.

PMID- 11286183
TI  - [The public professional duties of the physician. From the series of lectures on
      "Physician legal information" organized by the Central Committee for Physician
      Continuing Education in Prussia. 1905].

PMID- 11286182
TI  - [The effect of selected factors on the course of wound healing after surgery for
      laryngeal neoplasms].
AB  - Finding of the a etiologic factors and participation of bacteria flora in wound
      healing in laryngeal cancer treatment was the purpose of our study.
      Investigations were performed in 27 patients. Swabs were taken from the
      postoperative wounds. Detailed identifications of the bacteria flora and
      antibiotic susceptibility of bacteria were performed. Wound healing was estimated
      according to extension of the carcinoma, applied antibiotics, state of the oral
      cavity, the kind of bacteriological flora isolated after surgical treatment from
      postoperative wounds. It was found that wound healing depended on the extension
      of carcinoma, as well as, type of isolated bacteria and antibiotic therapy used.
      The proper healing of postoperative wounds was not dependent on the state of the
      oral cavity and the dentition. The main cause of postoperative complication of
      wounds was methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 11286184
TI  - A Nobel Prize for cell biology.

PMID- 11286185
TI  - European Best Practice Guidelines for Renal Transplantation (part 1).

PMID- 11286187
TI  - Arterial Thrombosis: from Mechanisms to Treatment. Proceedings of the XIII Paavo
      Nurmi Symposium. 1-3 September 2000, Espoo, Finland.

PMID- 11286186
TI  - [Theoretical problems of Hungarian family planning in the last few decades.
      1975].

PMID- 11286188
TI  - Cell: sporozoite interactions and invasion by apicomplexan parasites of the genus
      Eimeria.
AB  - The site specificity that avian Eimeria sporozoites and, to a more limited
      degree, other apicomplexan parasites exhibit for invasion in vivo suggests that
      specific interactions between the sporozoites and the target host cells may
      mediate the invasion process. Although sporozoite motility and structural and
      secreted antigens appear to provide the mechanisms for propelling the sporozoite
      into the host cell,there is a growing body of evidence that the host cell
      provides characteristics by which the sporozoites recognise and interact with the
      host cell as a prelude to invasion. Molecules on the surface of cells in the
      intestinal epithelium, that act as receptor or recognition sites for sporozoite
      invasion, may be included among these characteristics. The existence of receptor
      molecules for invasion by apicomplexan parasites was suggested by in vitro
      studies in which parasite invasion was inhibited in cultured cells that were
      treated with a variety of substances designed to selectively alter the host cell
      membrane. These substance included cationic compounds or molecules, enzymes that
      cleave specific linkages, protease inhibitors, monoclonal antibodies, etc. More
      specific evidence for the presence of receptors was provided by the binding of
      parasite antigens to specific host cell surface molecules. Analyses of host cells
      have implicated 22, 31, and 37 kDa antigens, surface membrane
      glycoconjugates,conserved epitopes of host cells and sporozoites, etc., but no
      treatment that perturbs these putative receptors has completely inhibited
      invasion of the cells by parasites. Regardless of the mechanism,sporozoites of
      the avian Eimeria also invade the same specific sites in foreign host birds that
      they invade in the natural host. Thus, site specificity for invasion may be a
      response to characteristics of the intestine that are shared by a number of hosts
      rather than to a unique trait of the natural host. Protective immunity elicited
      against avian Eimeria species is not manifested in a total blockade of parasite
      invasion. In fact, the effect of immunity on invasion differs according to the
      eliciting species and depends upon the area of the intestine that is invaded.
      Immunity produced against caecal species of avian Eimeria, for example Eimeria
      tenella and Eimeria adenoeides, inhibits subsequent invasion by homologous or
      heterologous challenge species, regardless of the area of the intestine that the
      challenge species invade. Conversely, in birds immunised with upper intestinal
      species, Eimeria acervulina and Eimeria meleagrimitis, invasion by challenge
      species is not decreased and often is significantly increased.

PMID- 11286189
TI  - Baroreflex control of heart rate during exercise: a topic of perennial conflict.

PMID- 11286191
TI  - AIDS in China.

PMID- 11286190
TI  - A new home for infection research.

PMID- 11286192
TI  - The origins and evolution of viruses.

PMID- 11286193
TI  - Why does Helicobacter pylori actually have Lewis antigens?

PMID- 11286195
TI  - British Society of Gastroenterology annual meeting. 18-21 March 2001. Glasgow,
      United Kingdom. Abstracts.

PMID- 11286194
TI  - The role of CFTR protein susceptibility to bacterial infections in cystic
      fibrosis.

PMID- 11286196
TI  - Peter Singer and Telford Taylor: what questions do they raise for us all?

PMID- 11286198
TI  - Acute Leukemias IX: Basic Research, Experimental Approaches and Novel Therapies.
      February 24-28, 2001. Munich, Germany. Abstracts.

PMID- 11286197
TI  - 5th International Conference of Nuclear Cardiology. May 2-5, 2001. Vienna,
      Austria. Abstracts.

PMID- 11286199
TI  - 45th Annual meeting of the GTH (Gesellschaft fur Thrombose- und
      Hamostaseforschung). February 14-17, 2001. Dusseldorf, Germany. Abstracts.

PMID- 11286200
TI  - Experimental Biology 2001. Orlando, Florida, USA. March 31-April 4, 2001.
      Abstracts, part II.

PMID- 11286201
TI  - Domestic violence screening rate leaves much to be desired.

PMID- 11286202
TI  - 2000 Index issue. Cumulative indexes for volumes 267-279.

PMID- 11286204
TI  - Pathological Society of Great Britain and Ireland 182nd meeting. 3-5 January
      2001. Maastricht, The Netherlands. Abstracts.

PMID- 11286203
TI  - Non-invasive management of Ascaris lumbricoides biliary tact migration: a
      prospective study in 69 patients from Ecuador.
AB  - Ascariasis is one of the most common helminthic diseases. Its most feared
      complication is migration into the biliary tree. Some authors recommend immediate
      duodenoscopy in all cases of biliary migration, with sphincterotomy for the
      extraction of the parasites, and surgical extraction in case of intrahepatic
      ascariasis. We followed prospectively 69 patients with ultrasonographical
      evidence of migration. Initial treatment consisted of intravenous analgesics and
      antispasmodics, and albendazole 800 mg by mouth. Only patients with persisting
      symptoms or with high amylasaemia underwent duodenoscopy, with extraction in case
      of a visible worm. Surgery was limited to cases with persistent or progressive
      complications. In 97% of our cases the worms disappeared with noninvasive therapy
      alone. A duodenoscopy was done in 30 (42%) cases; in 10 (14%) a worm was found in
      the ampulla of Vater and extracted without sphincterotomy. In none of the 6 cases
      with A. lumbricoides in the intrahepatic biliary tree did the parasite persist.
      Only one patient required surgical intervention. Treatment of A. lumbricoides
      migration to the biliary tract should be principally medical. Duodenoscopy with
      extraction of a visible worm should be limited to cases with persisting pain
      and/or hyperamylasaemia. Invasive methods like sphincterotomy and surgery should
      be restricted to patients who do not respond to conservative treatment.

PMID- 11286205
TI  - Hydrochemical distribution patterns in stream waters, Trondelag, central Norway.
AB  - A regional geochemical sampling program of stream waters has been carried out in
      the Nord-Trondelag region of central Norway. This area has hitherto been little
      affected by regional anthropogenic sources of pollution. Hydrochemical trends
      appear to be dominated by interplay of two main factors: (i) input of sea salts
      via marine aerosols in precipitation: and (ii) geological sources (mineral
      weathering). Factor (i) results in a predominance of Na-Cl waters near the coast,
      and may also be partially responsible (via proton displacement from soil ion
      exchange sites by marine cations) for lower pH values in near-coastal waters.
      Further inland, the importance of marine salts decreases and waters become
      dominantly Ca-(Na)-HCO3. Sub-regional anomalies in geochemical maps for, e.g.
      nitrate and copper may indicate anthropogenic sources for these parameters from
      agriculture or mining activities.

PMID- 11286206
TI  - Atmospheric and children's blood lead as indicators of vehicular traffic and
      other emission sources in Mumbai, India.
AB  - Average concentration of Pb in atmospheric air particulates in different suburbs
      of Mumbai was studied for almost a decade and its spatial and temporal profiles
      are discussed in relation to emission sources. In general the concentration of Pb
      in all the residential suburban atmosphere is well below the Central Pollution
      Control Board (CPCB, 1994) prescribed limit of 1.5 microg m(-3) barring a few
      exceptions for some residential/industrial sites, such as those of Thane and
      Kurla scrap yards. The correlation between blood lead of children and air lead
      reveals that the blood Pb level in children could increase by 3.6 microg dl(-1)
      for an incremental rise of 1.0 microg Pb m(-3) of air. The temporal profile of
      air Pb values indicates a decreasing trend in residential suburbs (Khar: 1984,
      0.39 microg m(-3); 1996, 0.17 microg m(-3)) as well as in suburban residential
      areas with low traffic (Goregaon: 1984, 0.53 microg m(-3); 1996, 0.30 microg m(
      3)).

PMID- 11286207
TI  - The availability of plutonium and americium in Irish Sea sediments for re
      dissolution.
AB  - The availability of plutonium and americium, for re-dissolution from offshore
      sediments into Irish Sea water, has been examined. Sediments collected from the
      mud-patch near the Cumbrian coast were characterized in terms of spatial
      location, particle size, partitioning of radionuclides with respect to physico
      chemical bonds and availability of actinides for release into seawater.
      Sequential extraction investigations revealed that plutonium was predominantly
      associated with strongly bound sesquioxide and organic complex fractions.
      Americium was associated mainly with the organic complex fraction, but a
      significant fraction was in carbonate form. Sediment/water re-dissolution
      experiments with and without stirring were compared to simulate the effect of
      disturbing bed sediment. After 1 week, neither set of re-dissolution data
      provided significant trends between dissolved activity and time. Stirred systems
      appeared to release 2.5 times more plutonium and americium into seawater than
      unstirred systems. Measured 239,240Pu and 241Am distribution coefficients (Kd
      values) were both typically approximately 10(5) l kg(-1). 241Am Kd values are an
      order of magnitude lower than previously reported for the north-eastern Irish
      Sea, but similar to western Irish Sea values. Overall, the fractions of plutonium
      and americium available for re-dissolution from bed sediment are very low at <
      0.1%, with proportionally more plutonium being released than americium. These
      findings lend further support for the extrapolation of laboratory-derived
      information to environmental conditions.

PMID- 11286208
TI  - A multi-element profile of housedust in relation to exterior dust and soils in
      the city of Ottawa, Canada.
AB  - This paper presents multi-element profiles of indoor dust versus exterior soils
      and dusts from 50 residences located in 10 neighborhoods across Ottawa, the
      capital city of Canada. Mercury concentrations were determined using nitric
      sulphuric acid digestion and cold vapor AAS. Concentrations of 31 other elements
      were determined using nitric-hydrofluoric acid digestion and ICP-MS. Comparisons
      of household dust, garden soil and street dust at the individual residence scale
      and at the community scale were based on a consistent 100-250-microm particle
      size fraction. Results showed housedust samples to contain significantly higher
      concentrations of many key elements, including lead, cadmium, antimony and
      mercury, than either street dust or garden soil samples. Also, housedust profiles
      revealed a distinct multi-element signature in relation to exterior dust and soil
      samples. Interestingly, garden soil contained higher concentrations of aluminum,
      barium and thallium than either house or street dust. Geometric mean
      concentrations (mg/kg) of these elements in household dust/garden soil were: lead
      233/42; cadmium 4.42/0.27; antimony 5.54/0.25; mercury 1.728/0.055; aluminum
      24281/55677; barium 454/763; and thallium 0.14/0.29. Street dust contained lower
      geometric mean concentrations than garden soil for 23 out of a total of 32
      elements. In general, indoor/outdoor concentration ratios varied widely from one
      element to another, and from one residence to another within the community. In
      the case of Ottawa, which is a city with a low concentration of heavy industries,
      it would be difficult-to-impossible to accurately predict indoor dust
      concentrations based on exterior soil data. It is concluded that dust generated
      from sources within the house itself can contribute significantly to exposures to
      certain elements, such as lead, cadmium, antimony and mercury.

PMID- 11286209
TI  - Can one use ambient air concentration data to estimate personal and population
      exposures to particles? An approach within the European EXPOLIS study.
AB  - The objective of this paper is to devise a way to facilitate the use of fixed air
      monitors data in order to assess population exposure. A weighting scheme that
      uses the data from different monitoring sites and takes into account the time
      activity patterns of the study population is proposed. PM2.5 personal monitoring
      data were obtained within the European EXPOLIS study, in Grenoble, France (40
      adult non-smoking volunteers, winter 1997). Volunteers carried PM2.5 personal
      monitors during 48 h and filled in time-activity diaries. Workplaces and places
      of residence were classified into two categories using a Geographic Information
      System (GIS): some volunteers' life environments are seen as best represented by
      PM10 ambient air monitors located in urban background sites; others by monitors
      situated close to high traffic density sites (proximity sites). Measurements from
      the Grenoble fixed monitoring network using a TEOM PM10 sampler were available
      across the same period for these two types of sites (PM10block and PM10prox).
      These data were used to compute a translator parameter deltai that forces the
      measured PM2.5 personal exposures (PM2.5persoi) to equate the average PM10 urban
      ambient air concentrations ([PM10back + PM10prox]/2) measured the same days.
      Average deltai was 4.2 microg/m3 (CI95%[-3.4; 11.9]), with true average PM2.5
      personal exposure being 36.2 microg/m3 (28.2; 44.1). PM10 ambient levels at the
      proximity site and at the background site were respectively PM10prox = 43.8
      microg/m3 (37.1; 50.6) and PM10back = 37.0 microg/m3 (31.8; 42.3). In order to
      assess the consistency of this approach, six scenarios of 'proximity' and
      'background' environments were accommodated, according to traffic intensity and
      road distance. Deltai was estimated for the entire EXPOLIS population and for
      subgroups, using terciles based on the percentage of time spent in proximity by
      each subject. Other similar studies need to be conducted in different urban
      settings, and with other pollutants, in order to assess the generalizability of
      this simple approach to estimate population exposures from air quality
      surveillance data.

PMID- 11286211
TI  - Lead and cadmium in eggs of colonially nesting waterbirds of different position
      in the food chain of Greek wetlands of international importance.
AB  - Lead and cadmium concentrations were measured in eggs of collonially nesting
      waterbirds with different position in the food chains of Greek wetlands of
      international importance. Differences were found between species in the levels of
      both lead and cadmium in the Evros and Axios Deltas attributable to their
      different diets. Nevertheless, the concentration in eggs was unrelated to the
      position of each species studied in its food chain. There was no significant
      difference in lead levels among four wetlands sampled for the cormorant and in Cd
      levels among three wetlands sampled for the Mediterranean gull, probably implying
      species-specific accumulation patterns. A higher lead pollution of the Axios
      Delta area was only reflected in the eggs of the Mediterranean gull. The very low
      concentrations of both metals found in the eggs may either suggest low
      environmental inputs or lack of sensitivity in using eggs as lead and cadmium
      biomonitors, thus a more sensitive bioindicator still remains to be found.

PMID- 11286210
TI  - The Mt. Diwata study on the Philippines 1999--assessing mercury intoxication of
      the population by small scale gold mining.
AB  - The region of Diwalwal, dominated by Mt. Diwata, is a gold rush area on Mindanao
      (Philippines) where approximately 15000 people live. The fertile plain of Monkayo
      is situated downstream, where people grow crops such as rice and bananas; locally
      caught fish is eaten frequently. The ore is dug in small-scale mines and ground
      to a powder by ball-mills while still in Diwalwal. The gold is then extracted by
      adding liquid mercury (Hg), forming gold-amalgam. To separate the gold from the
      Hg, in most cases the amalgam is simply heated in the open by blow-torches. A
      high external Hg burden of the local population must be assumed. To evaluate the
      internal Hg burden of the population and the extent of possible negative health
      effects, 323 volunteers from Mt. Diwalwal, Monkayo and a control group from Davao
      were examined by a questionnaire, neurological examination and neuro
      psychological testing. Blood, urine and hair samples were taken from each
      participant and analyzed for total Hg. A statistical evaluation was possible for
      102 workers (occupationally Hg burdened ball-millers and amalgam-smelters), 63
      other inhabitants from Mt. Diwata ('only' exposed from the environment), 100
      persons, living downstream in Monkayo, and 42 inhabitants of Davao (serving as
      controls). The large volume of data was reduced to yes/no decisions. Alcohol as a
      possible bias factor was excluded (level of alcohol consumption and type, see
      Section 4.4). Each factor with a statistically significant difference of at least
      one exposed group to the control group was included in a medical score (0-21
      points). In each of the exposed groups this score was significantly worse than in
      the control group (median control, 3; downstream, 9; Mt. Diwata, non-occupational
      exposed, 6; Hg workers, 10). In comparison to the surprisingly high Hg
      concentration in blood (median, 9.0 microg/l; max, 31.3) and in hair (2.65
      microg/g; max, 34.7) of the control group, only the workers show elevated levels:
      Hg-blood median 11.4, max 107.6; Hg-hair median 3.62, max 37.8. The Hg urine
      concentrations of the occupational exposed and non-exposed population on Mt.
      Diwata was significantly higher than in the control group: control median 1.7
      microg/l, max 7.6; non-occupational burdened median 4.1, max 76.4; and workers
      median 11.0, max 294.2. The participants, living downstream on the plain of
      Monkayo show no statistically significant difference in Hg-blood, Hg-urine or Hg
      hair in comparison with the control group. The German Human-Biological-Monitoring
      value II (HBM II) was exceeded in 19.5% (control), 26.0% (downstream), 19.4% (Mt.
      Diwata, non-occupational) and 55.4% (workers) of the cases, the German
      occupational threshold limit in 19.6% of the workers. Only some of the clinical
      data, characteristic for Hg intoxication (e.g. tremor, loss of memory, bluish
      discoloration of the gingiva, etc.), correlate with Hg in blood or urine, but not
      with Hg in hair. The medical score sum correlates only with Hg in urine. The poor
      correlation between the Hg concentration in the biomonitors to classic clinical
      signs of chronic Hg intoxication may be explained by several factors: Hg in
      blood, urine and hair do not adequately monitor the Hg burden of the target
      tissues, especially the brain. Inter-individual differences in the sensitiveness
      to Hg are extremely large. In this area a mixed burden of Hg species must be
      assumed (Hg vapor, inorganic Hg, methyl-Hg). Chronic Hg burden may have
      established damage months or even years before the actual determination of the Hg
      concentrations in the bio-monitors under quite different burden was performed
      (Drasch G. Mercury. In: Seiler HG, Sigel A, Sigel H, editors. Handbook on metals
      in clinical and analytical chemistry. New York: Marcel Dekker, 1994:479-494).
      Therefore, a 'Hg intoxication', that should be treated, was not diagnosed by the
      Hg concentration in the bio-monitors alone, but by a balanced combination of
      these Hg values and the medical score sum. In principle, this means the higher
      the Hg concentration in the bio-monitors, the lower the number of characteristic
      adverse effects are required for a positive diagnosis. By this method, 0% of the
      controls, 38% downstream, 27% from Mt. Diwata, non-occupational exposed and 71.6%
      of the workers were classified as Hg intoxicated. A reduction of the external Hg
      burden on Mt. Diwata is urgently recommended. An attempt to treat the intoxicated
      participants with the chelating agent dimercaptopropanesulfonic acid (DMPS) is
      planned.

PMID- 11286212
TI  - Effect of cigarette smoke on seed germination.
AB  - The effect of cigarette smoke was studied on the germination of radish, kale,
      lettuce, amaranth, wheat, rice, barley and rye seeds. It was found that such
      smoke markedly retarded, in all cases, the rate of germination. Furthermore,
      cigarette smoke caused a retardation of the levels of certain enzymes (alpha
      amylase or lysozyme) known to be significant in the germination of these seeds.

PMID- 11286213
TI  - The importance of ligand speciation in environmental research: a case study.
AB  - The speciations of EDTA and DTPA in process, waste and river waters are modelled
      and simulated, specifically to the mode of occurrence in the pulp and paper mill
      effluents and subsequently in receiving waters. Due to relatively short residence
      times in bleaching process and waste water treatment and slow exchange kinetics,
      it is expected that the thermodynamic equilibrium is not necessarily reached.
      Therefore, the initial speciation plays a key role. As such, the simulations have
      been extended to the process waters of the pulp and paper industry taking into
      account estimated average conditions. The results reveal that the main species
      are; Mn and Ca complexes of EDTA and DTPA in pulp mill process waters; Fe(III)
      and Mn complexes of EDTA and DTPA in waste waters; Fe(III) and Zn complexes of
      EDTA and DTPA in receiving waters. It is also shown how the increasing
      concentration of complexing agents effects the speciation. Alkaline earth metal
      chelation plays a significant role in the speciation of EDTA and DTPA when there
      is a noticeable molar excess of complexing agents compared with transition
      metals.

PMID- 11286214
TI  - Transfer of iodine from soil to cereal grains in agricultural areas of Austria.
AB  - The concentrations of iodine in cereal grains cultivated at 38 locations in
      Austria from cereal-producing sites in agricultural areas and soil-to-grain
      transfer factors (TF) were determined. The concentrations of iodine in cereal
      grains, which were analyzed by radiochemical neutron activation analysis ranged
      from 0.002 to 0.03 microg g(-1), the arithmetic mean and the median were 0.0061
      microg g(-1) and 0.0046 microg g(-1), respectively. The TF values for cereal
      grains were calculated to be 0.0005-0.02 and the median was 0.0016. The TF values
      correlated positively with the iodine concentrations in cereal grains. However,
      the TF values correlated negatively with the iodine concentrations in soils as
      well as with the amount of clay contents of soils. The TF values were almost
      independent on pH values (5.4-7.6) of soils.

PMID- 11286215
TI  - Indoor and outdoor BTX levels in German cities.
AB  - On the basis of the ongoing study INGA (INdoor exposure and Genetics in Asthma),
      Germany's most detailed and standardized epidemiological study on indoor exposure
      to both allergens in house dust and volatile compounds in the air of the home
      environment has been performed. The purpose of this paper is to describe the
      spatial and seasonal variability of indoor and outdoor BTX (Benzene, toluene,
      ethyl benzene, ortho-xylene, meta- and para-xylene) concentrations for the study
      period from June 1995 to November 1996. Within this framework, air concentrations
      of volatile organic compounds (BTX) were measured in 204 households in Erfurt
      (Eastern Germany) and 201 households in Hamburg (Western Germany). BTX sampling
      was conducted over one week using OVM 3500 passive diffusion sampling devices in
      the indoor (living room and bedroom) and outdoor environment (outside the window
      of the living room). Indoor and outdoor median BTX concentrations in Erfurt were
      slightly, but significantly higher than those in Hamburg. This gap was most
      pronounced in the levels of indoor toluene (37.3 microg/m3 for Erfurt and 20.5
      microg/m3 for Hamburg, P < 0.0001). In both cities, winter indoor and outdoor
      concentrations for the five compounds exceeded the summer values. Outdoor
      concentrations of ethyl benzene and ortho-xylene were very low (50% < L.D.). In
      general, the indoor BTX air concentrations were significantly higher than the
      outdoor concentra- tions, the lowest I/O ratios were found in the case of
      benzene. Living room and bedroom values for the five compounds were highly
      correlated (Spearman coefficient 0.5-0.9). Despite the better insulation of the
      homes in West Germany, no indication for the expected higher indoor
      concentrations of BTX in the West could be found. The strong and yet undiscovered
      indoor source for toluene in East Germany might lead to a further increase in the
      indoor air load in those homes in the East, which undergo renovations which will
      lead to improved insulation.

PMID- 11286216
TI  - A dynamic compartmental food chain model of radiocaesium transfer to Apodemus
      sylvaticus in woodland ecosystems.
AB  - A study was undertaken to quantify the activity concentrations of 137Cs in
      Apodemus sylvaticus (the woodmouse) in two woodland sites, Lady Wood and Longrigg
      Wood, adjacent to British Nuclear Fuels Ltd. (BNFL) Sellafield, Cumbria, UK. A
      deterministic dynamic compartmental food chain model was also constructed to
      predict 137Cs activity concentration [Bq kg(-1) dry weight (dw)] in A. sylvaticus
      on a seasonal basis given the activity concentrations in its diet. Within the
      coniferous woodland site (Lady Wood), significant differences were found between
      seasons (P < 0.05, summer vs. autumn cohort; P < 0.001, spring vs. autumn
      cohort), with an autumn peak in activity concentration (geometric mean = 140
      x/divided by 2.3 Bq kg(-1) dw) being attributed to mycophagy. Fungal
      concentrations ranged from 2-3213 Bq kg(-1) dw. The modelled activity
      concentrations fell between the confidence intervals of the observed data in four
      of the six seasonal cohorts sampled. Disparities between predicted and observed
      activity concentrations are attributed to uncertainties surrounding the
      fundamental feeding ecology of small mammals.

PMID- 11286217
TI  - Concentrations and distribution of some polychlorinated biphenyls (PCBs) and
      polycyclic aromatic hydrocarbons (PAHs) in an ombrotrophic peat bog profile of
      Switzerland.
AB  - An efficient method was developed for the analysis of selected PCBs and PAHs in
      dry peat samples. The method includes a shaking extraction using acetone and
      hexane followed by the purification of the crude extract by gel permeation
      chromatography (GPC) which turned out to be the key clean-up step. The method was
      used to determine seven indicator PCBs and 16 EPA-PAHs in individual sections of
      an ombrotrophic peat core in south-west Switzerland. The maximum concentrations
      of PCBs (19 microg sigma PCBs/kg dm) were found at a peat depth of 10-15 cm which
      is estimated to correspond to a time period of 1976-1960 whereas the PAH profile
      showed a maximum (2853 microg sigma PAHs/kg dm) at a depth of 20-25 cm which
      represents circa 1951-1930. Compared to these maxima, the concentrations of PAHs
      in the top layer (1990-1986) are six times lower, but the decline in PCBs is only
      38%. The concentration profiles are generally consistent with known changes in
      contaminant emissions, and suggest that more detailed studies of ombrogenic peat
      bog profiles could be used for detailed reconstructions of the changing
      atmospheric fluxes of these and other organic contaminants.

PMID- 11286218
TI  - Environmental exposure to lead in a population of adults living in northern
      France: lead burden levels and their determinants.
AB  - As part of the assessment of a site in northern France polluted by metals from
      two smelters (in particular, lead, cadmium and mercury), a cross-sectional study
      was carried out which intended to estimate the levels of the lead burden of the
      adult population living on the site and the factors associated with these levels.
      The exposed zone included 10 municipalities in the Nord-Pas de Calais region,
      located in the vicinity of two non-ferrous metal smelters. The soils in these
      municipalities contained between 100 and 1700 ppm of lead. The non-polluted zone
      contained 20 municipalities from the same region, drawn randomly from those in
      the region of comparable size but free from any industrial lead exposure. The
      adult study population (301 men and 300 women) was stratified according to age,
      sex, employment status and exposure level. The inclusion criteria required
      subjects who were aged between 20 and 50 years and had been living in the exposed
      zone for at least 8 years; the exclusion criteria were pregnancy, cancer, kidney
      disease and diabetes. No more than 10% of the subjects participating could work
      at one of the two smelters. Data collection took place at home; visiting nurses
      interviewed subjects to complete a questionnaire and also took blood samples. The
      lead assay was performed by atomic absorption spectrometry. The geometric mean of
      the blood-lead levels was 74 microg/l, 95% CI = 69-80 among men and 49 microg/l,
      95% CI = 46-53 among women. Blood-lead levels exceeding 100 microg/l were found
      among 30% of men and 12% of women. Several factors were associated with variation
      of the mean blood-lead level: the blood-lead level was significantly higher among
      the men for subjects living less than 1 km from the smelters (geometric mean x
      1.3, 95% CI = 1.1-1.6), for those who drink alcoholic beverages (x 1.1, 95% CI =
      1.0-1.2 for consumption of 30 g/day), those who smoke (x 1.2, 95% CI = 1.0-1.3
      for 20 cigarettes/day), and for subjects with occupational exposure; among the
      women, for subjects living less than 1 km from the smelters (geometric mean x
      1.5, 95% CI = 1.2-1.7), for those who drink alcohol (x 1.1, 95% CI = 1.1-1.2 for
      a daily consumption of 10 g), and for women living in a building constructed
      before 1948 (x 1.2, 95% CI = 1.0-1.4).

PMID- 11286219
TI  - The nomenclature of major histocompatibility complex class I gene regulatory
      regions -- the case of two different downstream regulatory elements.

PMID- 11286220
TI  - Experimental Biology 2001. Orlando, Florida, USA. March 31-April 4, 2001.
      Abstracts, part I.

PMID- 11286221
TI  - Splenectomy and hemopoietic stem cell transplantation for myelofibrosis.

PMID- 11286222
TI  - Flow cytometry cannot assess surface binding of perforin to target cells.

PMID- 11286223
TI  - Risk for cytomegalovirus disease in patients receiving polymerase chain reaction
      based preemptive antiviral therapy after allogeneic stem cell transplantation
      depends on transplantation modality.

PMID- 11286224
TI  - Significance of neutrophil elastase mutations versus G-CSF receptor mutations for
      leukemic progression of congenital neutropenia.

PMID- 11286225
TI  - Drug-dependent antibodies against the prodrug carbimazole do not react with the
      metabolite thiamazole.

PMID- 11286226
TI  - BCR-ABL rearrangement is not detectable in essential thrombocythemia.

PMID- 11286227
TI  - Increase in platelet count in response to rHuEpo in a patient with
      thrombocytopenia and absent radii syndrome.

PMID- 11286228
TI  - Y Lacourciere, L Poirier, J Lefebvre. A comparative review of the efficacy of
      antihypertensive agents on 24 h ambulatory blood pressure. Can J Cardiol
      2000;16:1155-1166.

PMID- 11286230
TI  - Richard J. Davidson. Award for distinguished scientific contributions.

PMID- 11286229
TI  - Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen
      storage disease type II: results of a phase I/II clinical trial.
AB  - PURPOSE: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic
      muscle disorder caused by deficiency of acid alpha-glucosidase (GAA). The purpose
      of this study was to investigate the safety and efficacy of recombinant human GAA
      (rhGAA) enzyme therapy for this fatal disorder. METHODS: The study was designed
      as a phase I/II, open-label, single-dose study of rhGAA infused intravenously
      twice weekly in three infants with infantile GSD-II. rhGAA used in this study was
      purified from genetically engineered Chinese hamster ovary (CHO) cells
      overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary,
      neurologic, and motor functions were evaluated during 1 year of the trial period.
      The primary end point assessed was heart failure-free survival at 1 year of age.
      This was based on historical control data that virtually all patients died of
      cardiac failure by 1 year of age. RESULTS: The results of more than 250 infusions
      showed that rhGAA was generally well tolerated. Steady decreases in heart size
      and maintenance of normal cardiac function for more than 1 year were observed in
      all three infants. These infants have well passed the critical age of 1 year
      (currently 16, 18, and 22 months old) and continue to have normal cardiac
      function. Improvements of skeletal muscle functions were also noted; one patient
      showed marked improvement and currently has normal muscle tone and strength as
      well as normal neurologic and Denver developmental evaluations. Muscle biopsies
      confirmed that dramatic reductions in glycogen accumulation had occurred after
      rhGAA treatment in this patient. CONCLUSIONS: This phase I/II first study of
      recombinant human GAA derived from CHO cells showed that rhGAA is capable of
      improving cardiac and skeletal muscle functions in infantile GSD-II patients.
      Further study will be needed to assess the overall potential of this therapy.

PMID- 11286231
TI  - E. Tory Higgins. Award for distinguished scientific contributions.

PMID- 11286232
TI  - Elizabeth S. Spelke. Award for distinguished scientific contributions.

PMID- 11286233
TI  - David H. Barlow. Award for distinguished scientific applications of psychology.

PMID- 11286234
TI  - Alan J. Christensen. Award for distinguished scientific early career
      contributions to psychology.

PMID- 11286235
TI  - Robert L. Goldstone. Award for distinguished scientific early career
      contributions to psychology.

PMID- 11286236
TI  - Thomas E. Joiner. Award for distinguished scientific early career contributions
      to psychology.

PMID- 11286237
TI  - Dario Maestripieri. Award for distinguished scientific early career contributions
      to psychology.

PMID- 11286238
TI  - Jeffrey G. Parker. Award for distinguished scientific early career contributions
      to psychology.

PMID- 11286239
TI  - Karen Wynn. Award for distinguished scientific early career contributions to
      psychology.

PMID- 11286240
TI  - Laura M. Mackner. Edwin B. Newman graduate research award.

PMID- 11286241
TI  - Simon H. Budman. Award for distinguished professional contributions to knowledge.

PMID- 11286242
TI  - Mathilda B. Canter. Award for distinguished contributions to applied psychology
      as a professional practice.

PMID- 11286243
TI  - Allan G. Barclay. Award for distinguished professional contributions to public
      service.

PMID- 11286244
TI  - Lillian Comas-Diaz. Award for distinguished senior career contributions to the
      public interest.

PMID- 11286245
TI  - Jeannette R. Ickovics. Award for distinguished early career contributions to
      psychology in the public interest.

PMID- 11286246
TI  - Mary P. Koss. Award for distinguished contributions to research in public policy.

PMID- 11286247
TI  - Sylvia Rosenfield. Award for distinguished career contributions to education and
      training.

PMID- 11286248
TI  - Roger P. Weissberg. Award for distinguished contributions of applications of
      psychology to education and training.

PMID- 11286249
TI  - Florence W. Kaslow. Award for distinguished contributions to the international
      advancement of psychology.

PMID- 11286250
TI  - Author and subject index: volumes 68-79 (January 1995-December 2000).

PMID- 11286251
TI  - European Conference on Cancer Strategies and Outcomes. 11-14 March 2001.
      Edinburgh, United Kingdom. Abstracts.

PMID- 11286252
TI  - Society of Cardiovascular Anesthesiologists 23rd annual meeting. Vancouver,
      British Columbia, Canada. May 5-9, 2001. Abstracts.

PMID- 11286253
TI  - Orthopaedic proceedings. 1999, 2000. Abstracts.

PMID- 11286254
TI  - Joint Congress of the Scandinavian and the German Physiological Societies. 10-13
      March 2001, Berlin, Germany. Abstracts.

PMID- 11286256
TI  - Biochemistry. Ribosome's inner workings come into sharper view.

PMID- 11286255
TI  - An unfortunate U-turn on carbon.

PMID- 11286257
TI  - Research reactors. German neutron source faces new demands.

PMID- 11286258
TI  - Conservation. No easy answers for biodiversity in Africa.

PMID- 11286259
TI  - Neurobiology. How cannabinoids work in the brain.

PMID- 11286260
TI  - Marine mammalogy. River dolphins add branches to family tree.

PMID- 11286261
TI  - Climate change. Early birds may miss the worms.

PMID- 11286262
TI  - Toxicology. Science only one part of arsenic standards.

PMID- 11286263
TI  - Peer review. NSF scores low on using own criteria.

PMID- 11286264
TI  - DNA arrays. Affymetrix settles suit, fixes mouse chips.

PMID- 11286265
TI  - Biomedical training. NIH pledges big hike in postdoc stipends.

PMID- 11286266
TI  - Nutrition. The soft science of dietary fat.

PMID- 11286267
TI  - Nutrition. What if Americans ate less saturated fat?

PMID- 11286268
TI  - Nutrition. The epidemic that wasn't?

PMID- 11286269
TI  - A comprehensive U.S. energy policy.

PMID- 11286270
TI  - A comprehensive U.S. energy policy.

PMID- 11286271
TI  - Portugal: a case history in S&T cooperation.

PMID- 11286272
TI  - Tracking antibiotics up the food chain.

PMID- 11286273
TI  - Taiwan seeks to solve its resistance problems.

PMID- 11286274
TI  - Antibiotic resistance affects plant pathogens.

PMID- 11286275
TI  - Developmental biology. Don't clone humans!

PMID- 11286277
TI  - Quantum physics. Standing room only at the quantum scale.

PMID- 11286276
TI  - Cancer.     A CINtillating new job for the APC tumor suppressor.

PMID- 11286278
TI  - Cell biology. Chewing the fat--ACC and energy balance.

PMID- 11286280
TI  - Atomic force microscopy.     You may squeeze the atoms but don't mangle the
      surface!

PMID- 11286279
TI  - Neuroscience. The song does not remain the same.

PMID- 11286281
TI  - Carbon cycle. Discriminating plants.

PMID- 11286282
TI  - Facilitative glucose transporters in livestock species.
AB  - The study of facilitative glucose transporters (GLUT) requires carefully done
      immunological experiments and sensitive molecular biology approaches to identify
      the various mechanisms which control GLUT expression at the RNA and protein
      levels. The cloning of species-specific GLUT cDNAs showed that GLUT4 and GLUT1
      diverge less among species than other GLUT isoforms. The key role of GLUT in
      glucose homeostasis has been demonstrated in livestock species. In vitro studies
      have suggested specific roles of GLUT1 and GLUT3 in avian cells. In vivo studies
      have demonstrated a regulation of GLUTs (especially of GLUT4) by nutritional and
      hormonal factors in pigs and cattle, in lactating cows and goats and throughout
      the foetal life in the placenta and tissues of lambs and calves. All these
      results suggest that any changes in GLUT expression and activity (such as GLUT4
      in muscles) could modify nutrient partitioning and tissue metabolism, and hence,
      the qualities of animal products (milk, meat).

PMID- 11286283
TI  - L-carnitine supplementation in breeding pigeons: impact on zootechnical
      performance and carnitine metabolism.
AB  - In the first experiment (Exp1), three consecutive breeding rounds were performed
      by two groups of six pigeon couples in order to study the impact of L-carnitine
      supplementation (80 mg x d(-1)) of parent pigeons on zootechnical performance.
      Both in the second and third experiments (Exp2, Exp3), one breeding round was
      performed by two groups of six pigeon couples to reveal the biochemical
      background of the increase in squab growth, the limitation of body weight
      decrease in male parent birds and the tendency for an improved cumulative feed
      efficiency due to L-carnitine supplementation in Exp1. Growth improvement of the
      squabs with L-carnitine was only seen when the parent pigeons were supplemented,
      together with a marked rise in the body weight of the parent birds around
      hatching. Based on the results of the crop milk analysis, growth improvement was
      probably due to a quantitative impact on crop milk production. The crop milk from
      the supplemented groups in both Exp2 and Exp3 had increased levels of carnitine.
      Carnitine, gamma-butyrobetaine and acetylcarnitine were increased in plasma
      samples of the supplemented parent pigeons. No differences were present in the
      squabs' plasma for these parameters. In the squabs of Exp3, no changes were seen
      in the proportional growth or the protein content of the heart, breast muscle and
      liver, but the breast muscle of the squabs from the supplemented group in Exp3
      showed a considerable rise in carnitine and a marked decrease in gamma
      butyrobetaine.

PMID- 11286284
TI  - Contribution of erythrocytes and plasma in threonine and lysine transfer across
      the portal drained viscera and the liver in pigs. Effect of threonine and lysine
      dietary supply.
AB  - Contributions of erythrocytes and plasma to threonine and lysine transport across
      the PDV and the liver were determined in growing pigs successively fed a
      threonine deficient diet and a control well-balanced diet (experiment 1) or a
      lysine deficient or a well-balanced diet (experiment 2). The animals were
      surgically prepared for insertion of chronic catheters in the mesenteric vein
      (MV), the portal vein (PV), a hepatic vein (HV) and the carotid artery (CA).
      Plasma and whole blood AA concentrations in PV, HV and CA and PV and HV blood
      flows were determined during 6 hours of para-aminohippuric acid constant
      infusion. During this period the pigs were continuously fed (1 meal per hour).
      The contribution of plasma to lysine and threonine transport was higher in pigs
      fed the well balanced diets. More than 50% of threonine and lysine appearing in
      the PV and in the HV are transported by the plasma. Our results suggest that
      erythrocytes are probably little involved in lysine and threonine transfer across
      the liver and digestive tract of pig continuously fed.

PMID- 11286285
TI  - Evidence that growth factors IGF-I, IGF-II and EGF can stimulate nuclear
      maturation of porcine oocytes via intracellular protein kinase A.
AB  - The aim of our in vitro experiments was to study the role of growth factors and
      protein kinase A (PKA)-dependent intracellular mechanisms in the control of
      nuclear maturation of porcine oocytes. Oocytes were cultured with or without
      growth factors (IGF-I, IGF-II, EGF; 10 ng x mL(-1) medium) and inhibitors of PKA
      (Rp-cAMPS or KT5720; 100 ng x mL(-1)). Stages of meiosis were determined from the
      structure of chromosomes after staining with Giemza. Intracellular levels of PKA
      were evaluated immunocytochemically using primary antisera against the PKA
      regulatory and catalytic subunits and by Western immunoblotting using primary
      antiserum against the PKA catalytic subunit. It was found that after 24 h culture
      the majority of oocytes had resumed nuclear maturation (they were at a stage of
      meiosis after diplotene) and that after 48 h culture the majority of cells had
      completed maturation (they had reached metaphase II of meiosis). Addition of IGF
      I, IGF-II or EGF, or a combination of IGF-I and EGF, significantly increased the
      proportion of oocytes which resumed and completed meiosis. Immunocytochemistry
      demonstrated a significant increase in the proportion of cells containing
      catalytic and, in some cases, the regulatory subunits of PKA after addition of
      IGF-I, IGF-II and EGF. Immunoblotting showed the presence of 2 forms of the PKA
      catalytic subunit within the oocytes (MW approximately 52 and 40 kD). EGF, but
      not IGF-I or IGF-II, increased the content of both isoforms. Inhibitors of PKA,
      when given alone, did not substantially influence the proportion of oocytes which
      resumed or completed meiosis. However, Rp-cAMPS and KT5720 both prevented the
      stimulatory effects of IGF-I, IGF-II and EGF on the resumption and completion of
      oocyte maturation. The present observations suggest (1) that IGF-I, IGF-II and
      EGF are potent stimulators of both resumption and completion of porcine oocyte
      nuclear maturation, (2) that PKA is present in oocytes, and (3) that PKA
      dependent intracellular mechanisms can mediate the action of growth factors on
      porcine oocytes.

PMID- 11286286
TI  - GH and IGF-I binding sites in adipose tissue, liver, skeletal muscle and ovaries
      of feed-restricted gilts.
AB  - The influence of feed restriction on GH and IGF-I binding was examined in the
      cyclic gilt. IGF-1, IGFBPs, insulin and leptin levels in plasma were also
      measured. Twenty-four gilts whose oestrous cycle was synchronised were used. From
      day 3 to day 12, (with day 0 being the first day of oestrus) feed allowance was
      240% and 80% of the energy requirements for maintenance for well-fed (H) and
      restricted gilts (L) respectively. Six gilts in each group were treated with an
      antagonist of GnRH but the treatment had no effect on any reported measurements.
      Blood and tissue samples were collected on days 12 and 13 respectively. L gilts
      lost live weight whereas H gilts gained weight. Plasma IGF-I, insulin and leptin
      concentrations were lower in L than in H gilts whereas plasma IGFBP levels were
      not affected by feed restriction. The specific binding of 125I-bGH to adipose
      tissue, liver, skeletal muscle and ovary membranes did not differ significantly
      between H and L gilts. Specific binding of 125I-IGF-I to hepatic membranes was
      higher in L than in H gilts whereas it did not differ between the two groups in
      the other tissue membranes.

PMID- 11286287
TI  - Rumen effective degradability of amino acids from soybean meal corrected for
      microbial contamination.
AB  - Rumen degradation kinetics and effective degradability of individual amino acids,
      total analysed amino acids (TAA) and crude protein (CP) of soybean meal were
      measured on four rumen-cannulated wethers using the nylon bag technique.
      Microbial contamination of the incubated residues was corrected using a
      continuous 15N intraruminal infusion and isolated solid associated bacteria as a
      reference sample. TAA showed a lower soluble fraction (14.9 vs. 20.8%; P < 0.01),
      a similar insoluble-degradable fraction (79.0 vs. 79.2%) and a higher degradation
      rate (11.5 vs. 8.4% x h(-1); P < 0.05) than CP. As a consequence, effective
      degradability was similar for TAA and CP (74.7 vs. 75.7%). Degradability values
      of individual amino acids varied moderately (range: +/-6% of TAA degradability).
      Valine, isoleucine, leucine, alanine, aspartic acid and tyrosine showed
      significantly lower degradability than TAA, while the opposite effect was
      observed for histidine, threonine and glutamic acid. Degradability of individual
      amino acids was related to their soluble fraction (r = 0.877; P<0.001).

PMID- 11286288
TI  - An immunohistochemical study on the regulation of estrogen receptor alpha by
      estradiol in the endometrium of the immature ewe.
AB  - The effects of estradiol-17beta (E2) on the expression of estrogen receptor alpha
      (ERalpha) in stromal and epithelial cells of endometrium in prepubertal lambs
      were investigated. Twenty three-month-old lambs were treated or not treated with
      one, two or three i.m. injections of E2 (1 microg x kg(-1)) in corn oil at
      intervals of 24 h. Lambs were slaughtered 12 or 24 h after the last injection. An
      immunohistochemical technique was used to visualize ERalpha immunostaining which
      was then analyzed quantitatively by a computer imaging analysis system. Seven
      endometrial compartments defined by cell type and location were analyzed
      separately. Positive staining of ERalpha was seen in the nuclei of stromal and
      epithelial cells. Glandular epithelium located next to the myometrium was stained
      more intensely than that next to the luminal epithelium and this phenomenon was
      maintained during treatment. Significantly less immunostaining was found in
      stromal cells 12 and 24 h after the first injection compared to the control
      group. A similar pattern was found in the glandular epithelium, although the
      decrease was more pronounced and the restoration of ERalpha was faster. This
      study shows that E2 treatment down regulates ERalpha in the endometrium
      temporarily in both stromal and epithelial cells, but the characteristics of this
      effect seems to be cell type specific.

PMID- 11286289
TI  - Activation of avian embryo formation by unfertilized quail germ discs: comparison
      with early amphibian development.
AB  - In the present study we placed germ discs (or fragments containing the deep
      central part of it) from unfertilized laid or extracted quail eggs on the deep
      side of the upper layer of isolated anti-sickle regions from unincubated chicken
      blastoderms. After culture in vitro of associations where the central deep part
      of the germ discs was in contact with the deep side of the upper layer (UL), we
      observed in about 30% of the cases the onset of embryonic development. Both
      associated parts play a role in the final formation of an embryo. Our
      experimental results, suggest that the delta ooplasm of the nucleus of Pander
      influences the cranial upper layer to segregate an endophyll layer. The
      definitive embryonic structures i.e. mesoderm, epiblast and neural plate are
      derived from the chicken upper layer by respectively normal gastrulation and
      (pre)neurulation phenomena. Our experiments seem to have some homology with the
      association experiments of isolated cortices from various regions of unfertilized
      Xenopus eggs implanted into the ventroequatorial core of a recipient 8-cell
      Xenopus embryo.

PMID- 11286290
TI  - Health care social workers' views of ethical issues, practice, and policy in end
      of-life care.
AB  - End-of-life care decision making is perhaps the most difficult practice situation
      faced by health care social workers. Complex ethical issues arise from decisions
      regarding use of advancing medical technologies and/or other artificial
      treatments that may prolong life and/or compromise its quality. NASW has set
      forth a policy to help guide social workers dealing with end-of-life care
      decisions and the preservation of client self-determination in these situations.
      However, the present study (N = 63) revealed that a majority (57%) of social
      workers were not aware of the existence of, or were only somewhat familiar with
      the policy. Ethical dilemmas most often faced in end-of-life care situations
      related primarily to issues of communication between and among patients,
      families, and professionals. Practitioners indicated that more specific practice
      guidelines and increased education regarding bioethics and issues of end-of-life
      care are needed to be effective in assisting patients and families in end-of-life
      decision making.

PMID- 11286291
TI  - The influence of religious and personal values on nursing home residents'
      attitudes toward life-sustaining treatments.
AB  - A cross-sectional survey design was used to interview 133 Jewish, Catholic and
      Protestant residents from 13 nursing homes to examine the influence of religious
      and personal values on attitudes toward life-sustaining treatments. Subjects on
      average were 83 years old, Caucasian and female, with more than half having
      Advance Directives (ADs). Jewish subjects, as well as those who relied on God,
      were better educated and more anxious about death, had significantly more
      positive attitudes toward life-sustaining treatments at the end-of-life. On the
      other hand, those who had implemented ADs desired fewer life-sustaining
      treatments. Findings demonstrate that understanding individual desires for life
      sustaining treatments is complex. Practitioners who provide education on end-of
      life decisions need to discuss a myriad of issues including individual religious
      and personal values and other characteristics in an effort to understand and
      respect treatment choices.

PMID- 11286292
TI  - Employment and health among older bereaved men in the normative aging study: one
      year and three years following a bereavement event.
AB  - Research has indicated that the negative effects of bereavement on health among
      elderly men occur within the first six to twelve months following a bereavement
      event while other studies indicate that the death of a loved one can have long
      term effects on social functioning and mental health (Arbuckle & DeVries, 1995;
      Vinick, 1983a). However, employment has been found to buffer the strain produced
      by stressful life events. The purpose of this study was to examine the
      differential effects of employment on physical and mental health between elderly
      men bereaved for one year and elderly men bereaved for two to three years. We
      selected two groups of men from the Normative Aging Study: those bereaved within
      the past year (N = 248) and those bereaved from two to three years (N = 262).
      Ordinary least squares multiple regression analyses examined the direct effect of
      employment, controlling for age, education, income, marital status, and stress,
      on physical and mental health among the two groups of men. Although there were no
      significant differences between the two groups of men, the results from the
      separate analyses indicated that employment had a direct positive effect on
      physical health among those bereaved for one year and those bereaved from two to
      three years, but no significant effects were observed on mental health. The
      results suggest that employment can benefit men soon after a bereavement event
      and also over a longer period of time, especially on physical health.
      Implications for clinical practice and future research are discussed.

PMID- 11286293
TI  - Knowledge and attitudes of health care social workers regarding advance
      directives.
AB  - This cross sectional investigation describes the knowledge and attitudes of
      health care social workers regarding advance directives and explores factors that
      influence them. As major contributors to quality patient care, the level of
      knowledge and attitudes held by health care social workers regarding health care
      policy mandates are important. Mail survey methods were used to collect data from
      a systematic random sample (n = 324) of social workers throughout one mid-western
      state. Results indicate that the majority of health care social workers have high
      to moderate levels of knowledge about advance directives and hold positive
      attitudes regarding the policy. Social workers with more experience working with
      the elderly had higher levels of knowledge. Those employed in nursing homes and
      hospice settings had more positive attitudes than did those working in other
      health care facilities.

PMID- 11286294
TI  - Ethical dilemmas in general hospitals: social workers' contribution to ethical
      decision-making.
AB  - Thirty-two hospital social workers, fourteen of them directors of social work
      services and eighteen direct practitioners, were interviewed about their
      perception of the factors influencing social workers' contribution to the
      resolution of ethical dilemmas in general hospitals in Israel. Findings revealed
      that while ethical decision-making in hospitals is an interdisciplinary process,
      social workers' contribution to the process is affected by rivalry between social
      workers and other members of the health team, personality differences, type of
      ward and the nature of the ethical dilemma. Participants of the study had quite a
      clear perception of their role and of the unique knowledge-base social work can
      offer, including knowledge of the individual and family life course,
      understanding and skills in coping with diseases, and systems thinking. In order
      to increase their influence in ethical decision-making, the hospital social
      workers felt they must put more effort into developing their relationships with
      the other professionals involved in ethical decision-making both by making
      themselves more indispensable and by making their contribution explicit through
      greater documentation of their activities. The findings also implied that in
      order to gain more power and be accepted as equal partners in multidisciplinary
      teams, hospital social workers should improve their communication skills when
      interacting with representatives of other heath care professions.

PMID- 11286295
TI  - Effects of trimebutine on intestinal motility after massive small bowel
      resection.
AB  - Effects of trimebutine maleate (TM) on intestinal motility in short bowel
      syndrome (SBS) were studied in conscious canines in both acute and chronic phases
      following 80% massive distal small bowel resection (MSBR). TM was administered
      orally to beagles with MSBR or as controls in the postprandial and fasting
      states, and given simultaneously with meals. Intestinal motility was measured
      using bipolar electrodes for approximately 1 month after the electrodes were
      implanted in each beagle and the data compared between treatment groups. When TM
      was given with meals, the postprandial period without duodenal migrating
      myoelectric (or motor) complexes (MMCs) was shorter than in those given meals
      only. When TM was given in the postprandial state in short bowel beagles, the
      initial duodenal MMCs occurred earlier, i.e. the postprandial period was shorter.
      Diarrhea did not occur in these beagles. When TM was given in the fasting state,
      duodenal MMCs occurred and propagated to the distal intestine. In conclusion,
      oral TM administration can produce a more appropriate intestinal condition for
      the next food intake and make enteral nutrition possible even in the acute phase
      after MSBR. Such feeding can be carried out without overloading gut function as a
      result of the modulation of gastrointestinal motility by TM.

PMID- 11286296
TI  - Endothelial factors involved in the bradykinin-induced relaxation of the guinea
      pig aorta.
AB  - Endothelial factors involved in the bradykinin (BK)-induced relaxation of the
      guinea-pig aorta were investigated using isolated aortic rings. In intact aortic
      rings, higher concentrations of BK (> or = 10(-7) M) produced contraction,
      possibly as a direct action on smooth muscle. This BK-induced contraction was
      enhanced either by Nw-nitro-L-arginine (NOLA), an inhibitor of the production of
      nitric oxide or by indomethacin (IND), an inhibitor of cyclooxygenase, but not by
      carbenoxolone (CX), a known inhibitor of gap junctions. In aortic rings
      contracted with noradrenaline, BK elicited a relaxation with two components; an
      initial fast relaxation followed by a gradually diminishing slow relaxation, both
      in an endothelium-dependent manner. The BK-induced relaxation was inhibited in a
      drug specific manner by either NOLA, IND or CX. NOLA either abolished the fast
      relaxation, or sometimes converted it into a contractile response. IND reduced
      the amplitude and duration of the relaxation, by inhibiting the fast relaxation
      and abolishing the following slow relaxation. CX reduced both components of the
      relaxation. In the presence of both NOLA and CX, the BK-induced relaxation was
      converted to a contractile response followed by an IND-sensitive slow relaxation.
      In the presence of NOLA and IND together, BK stimulation caused a contraction
      with no following relaxation. These results indicate that in aortic rings of the
      guinea-pig, BK stimulates endothelial cells to release nitric oxide and
      prostanoids that produce the fast and slow components of the relaxation
      respectively. The effects of CX suggest that the contribution of EDHF to the BK
      induced relaxation is weak.

PMID- 11286297
TI  - Transmural field stimulation-induced relaxation in the rat common hepatic artery.
AB  - Hepatic arteries are reportedly innervated by vasoconstrictor and vasodilator
      nerves. Experiments were carried out to investigate the possible involvement of
      calcitonin gene related peptide (CGRP) and nitric oxide as neurotransmitters
      during the relaxation of the rat common hepatic artery produced by transmural
      electrical field stimulation (ES). Common hepatic arteries were excised under
      ether-anesthesia from 6 weeks-old female rats, and isometric tensions recorded
      from endothelium-damaged ring preparations. In the presence of atropine and
      guanethidine, ES relaxed arteries which had been previously contracted with
      vasopressin. The relaxation response to ES was attenuated by either tetrodotoxin
      or capsaicin-pretreatment. CGRP induced a concentration-dependent relaxation,
      which was inhibited by the CGRP antagonist CGRP(8-37). The ES-induced relaxation
      was attenuated either slightly by the nitric oxide synthesis inhibitor L
      nitroarginine (L-NNA) or markedly by CGRP(8-37). The relaxation response was
      nearly abolished in the presence of both CGRP(8-37) and L-NNA. These results may
      indicate that the nerve stimulation-induced vasodilatation of the rat common
      hepatic artery is mediated mainly by CGRP and partly by nitric oxide.

PMID- 11286298
TI  - Further evidence that (+/-)-carteolol-induced relaxation is mediated by beta2
      adrenoceptors but not by beta3-adrenoceptors in the guinea pig taenia caecum.
AB  - The properties of the beta1- and beta2-adrenoceptor partial agonist (+/-)
      carteolol were investigated against the beta2- and beta3-adrenoceptors of the
      taenia caecum of the guinea pig. (--)-Isoprenaline and (+/-)-carteolol induced
      concentration-dependent relaxation in this tissue. The non-selective beta1- and
      beta2-adrenoceptor antagonist (+/-)-propranolol (10-100 nM), the selective beta2
      adrenoceptor antagonist ICI 118,551 (10-100 nM) and the non-selective beta1-,
      beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol (10-100nM), caused a
      concentration-dependent rightward shift of the concentration-response curves for
      (--)-isoprenaline and (+/-)-carteolol. Schild regression plot analyses carried
      out for (+/-)-propranolol against (--)-isoprenaline and (+/-)-carteolol gave pA2
      values of 8.35 and 8.24, respectively. Schild plot analyses of ICI 118,551
      against (--)-isoprenaline and (+/-)-carteolol gave pA2 values of 8.47 and 8.41,
      respectively. Schild plot analyses of (+/-)-bupranolol against (--)-isoprenaline
      and (+/-)-carteolol gave pA2 values of 8.47 and 8.53, respectively. Slopes of the
      Schild plots were not significantly different from unity. These results suggest
      that the relaxant effects of (+/-)-carteolol in the guinea pig taenia caecum are
      mediated by beta2-adrenoceptors but not by beta3-adrenoceptors.

PMID- 11286299
TI  - Aquaporin-1 expression in visceral smooth muscle cells of female rat reproductive
      tract.
AB  - The aquaporins (AQ-s) are a group of intrinsic membrane proteins which facilitate
      movement of water across cell membranes; their recent identification in the
      kidney has led to the reappraisal of the mechanisms and pathways of water
      movement across epithelia. Aquaporin-1, (CHIP-28) is reported distributed in
      cardiac myocytes and vascular smooth muscle cells of large arteries. A related
      protein, AQ-4, has been identified in the sarcolemma of skeletal muscle fibres.
      We report aquaporin expression in the cell membrane of smooth muscle cells of the
      rat genital tract; fluorescence immunohistochemistry of rat uterine (fallopian)
      tube and vagina demonstrated AQ-1 in visceral smooth muscle of these tissues. In
      the uterine tube, AQ-1 labelling is most pronounced in the innermost longitudinal
      and the inner cells of the circular muscle layer and is absent from the outer
      longitudinal muscle layer of the myosalpinx. The possibility of a specific role
      for AQ-1 in tubal transport by altering the tubal luminal diameter during the
      estrus cycle is suggested.

PMID- 11286300
TI  - Alpha-adrenoceptor-mediated penile erection in dogs: in vivo and in vitro
      observations.
AB  - We have evaluated the role of adrenergic components in the pelvic splanchnic
      nerve on the erectile function in the dog. Electrical stimulation of pelvic
      splanchnic nerves increased blood flow in the internal pudendal artery and also
      elevated the cavernous pressure. These increases were blocked in part by
      phentolamine or methylene blue, but not by propranolol or atropine. The effects
      of cholinergic and adrenergic agonists and antagonists on mechanical responses
      were also examined in muscle strips obtained from various arteries in the
      intrapelvic region including the internal pudendal artery. Norepinephrine induced
      contraction in the iliac artery and relaxation in the internal pudendal artery,
      and both the contraction and relaxation responses were blocked by phentolamine
      but not by propranolol. These findings suggest that in the dog, alpha-adrenergic
      components projected through the pelvic splanchnic nerve may contribute to penile
      erection, together with cyclic GMP-mediated mechanisms.

PMID- 11286301
TI  - Imaging of cardiac metabolism using radiolabelled glucose, fatty acids and
      acetate.
AB  - The heart metabolizes a wide variety of substrates such as free fatty acids,
      glucose, lactate, pyruvate, ketone bodies and amino acids, but under normal
      conditions, free fatty acids and glucose are the major sources of energy. In
      contrast, in ischaemia with less than normal delivery of oxygen, oxidative
      metabolism of free fatty acids is decreased and exogenous glucose becomes the
      preferred substrate and the production of energy mainly depends on anaerobic
      glycolysis. These metabolic changes under various pathophysiological conditions
      of the myocardium stress the importance of metabolism for the function of the
      heart and allow metabolic imaging of important cardiovascular diseases. For the
      detection of cardiac energy metabolism, three different tracers have been
      developed and validated; namely radiolabelled glucose, fatty acids and acetate.
      [18F]-fluorodeoxyglucose (FDG) is a glucose analogue and the initial uptake of
      [18F]-fluorodeoxyglucose is almost identical to that of glucose. After uptake,
      [18F]-fluorodeoxyglucose undergoes phosphorylation but, unlike glucose-6
      phosphate, FDG-6-PO4 does not undergo further metabolism and remains trapped in
      the myocardium. This trapping of FDG allows imaging of FDG by positron-emission
      tomography and single photon emission computed tomography (SPECT) cameras. Use of
      FDG for assessing acute and chronic ischaemic syndromes has been studied, but it
      is mainly used in clinical practice to assess dysfunction of viable myocardium,
      which has the ability to improve in function. FDG data have been shown to
      adequately predict regional and global function improvement after
      revascularization of patients with chronic left ventricular dysfunction and
      coronary artery disease (CAD). They can also be a powerful predictor of prognosis
      in these patients. Fatty-acid metabolism can be studied after labelling with 1
      123. Beta-methyl iodine phenylpentadecanoic acid is a structurally modified fatty
      acid, which is used to trace uptake of fatty acids in the myocardium. Similarly
      to the case with FDG distinct uptake patterns have been observed in patients with
      CAD, and preliminary data concerning detection of myocardial viability assessment
      of prognosis are available. Interesting data suggest that fatty-acid imaging is
      the most sensitive technique for assessing metabolic changes in patients with
      hypertrophic cardiomyopathy. [11C]-Acetate immediately enters the tricarboxylic
      acid (TCA) cycle and metabolism of [11C]-acetate is dependent solely on the TCA
      cycle activity. Because the TCA-cycle activity is directly coupled to myocardial
      oxygen consumption, clearance rates of [11C]-acetate are used to assess regional
      myocardial consumption of oxygen. [11C]-acetate imaging has been validated for
      normal subjects and patients with CAD and appears to be as effective as use of
      FDG for assessing viability. The unique feature of this technique is to measure
      the regional consumption of oxygen non-invasively. Thus myocardial metabolic
      imaging is a promising approach for achieving direct insight into the processes
      underlying functional abnormalities of the myocardium.

PMID- 11286302
TI  - Dobutamine stress echocardiography and the effects of trimetazidine on left
      ventricular dysfunction in patients with coronary artery disease.
AB  - Trimetazidine, a metabolic agent that is opening the way to a new class of 3
      ketoacyl coenzymeA thiolase inhibitors, has been shown to improve exercise
      tolerance and increase the ischaemic threshold in patients with effort angina,
      both in monotherapy or in combination with other anti-anginal drugs. The aim of
      this study was to assess the effects of oral trimetazidine on the ischaemic
      threshold and left ventricular dysfunction of patients with coronary artery
      disease. Dobutamine stress echocardiography was used, a technique that allows
      direct visualisation of localised left ventricular dysfunction that occurs as a
      result of ischaemia. Dobutamine increases heart rate and contractility thus
      augmenting oxygen demand. In coronary artery disease, this increased demand leads
      to metabolic changes responsible for decreased wall thickness and abnormal wall
      motion.

PMID- 11286303
TI  - Haemodynamic and metabolic agents in the treatment of stable angina: publication
      review.
AB  - Many patients with stable angina pectoris are over-treated with haemodynamic
      agents. Understanding the different mode of action of the metabolic agent
      trimetazidine offers us the opportunity to implement effective combination
      therapy. Patients who fail to respond to optimal haemodynamic and metabolic
      therapy should be considered for a revascularisation procedure, not random
      additional drug therapy.

PMID- 11286304
TI  - Anti-ischaemic efficacy and tolerability of trimetazidine administered to
      patients with angina pectoris: results of three studies.
AB  - Several clinical studies have compared the anti-ischaemic properties of
      trimetazidine used as monotherapy with those of standard anti-anginal therapy. In
      the treatment of uncontrolled angina pectoris, the addition of a metabolic agent
      such as trimetazidine to existing therapy with a haemodynamic agent would appear
      to confer advantages over the addition of a second haemodynamic agent. Here we
      report the results of three studies conducted in Poland, the Czech Republic and
      Hungary that provide additional evidence for the beneficial effects of combining
      trimetazidine with a conventional haemodynamic agent such as beta-blockers, long
      acting nitrate or calcium channel blockers. This combination provided significant
      benefits in terms of improved exercise capacity and decreased number of angina
      attacks along with a good tolerability profile.

PMID- 11286305
TI  - Metabolic energy metabolism in diabetes: therapeutic implications.
AB  - Diabetic alterations of myocardial metabolism result mainly from malfunctions of
      acetyl-coenzyme A carboxylase, carnitine-palmitoyl-transferase-I and pyruvate
      dehydrogenase inducing an overshoot of fatty acid oxidation that inhibits glucose
      oxidation. Gene expression of pyruvate-dehydrogenase and glucose transporters and
      depression of the third step of the mitochondrial respiratory chain also
      contribute to the diabetic alterations of myocardial metabolism. Ischaemic
      cardiovascular alterations are common and treatment is rarely successful in cases
      of diabetes since fatty acid oxidation is the costliest metabolic pathway for
      oxygen. Thus, in diabetes, aerobic glycolysis gradually shifts to anaerobic
      glycolysis under ischaemia, with accumulation of lactate and acid metabolites
      that in turn induce myocardial deterioration, Animal experiments have
      demonstrated that elective depression of activity of carnitine-palmitoyl
      transferase-I enzyme-activity promotes glucose oxidation and early rapid recovery
      of myocardial contractility, especially under diabetic conditions. To reduce
      diabetic alterations of myocardial metabolism, anti-diabetic treatment must be
      switched to insulin during the acute ischaemic and post-ischaemic period of
      coronary diseases. Trimetazidine optimizes energy metabolism by selectively
      inhibiting action of the 3-ketoacyl-coenzyme A thiolase enzyme involved in beta
      oxidation and inhibiting the overshoot of fatty oxidation. Trimetazidine, as the
      first 3-ketoacyl-coenzyme A thiolase inhibitor, therefore provides permanent
      myocardial cytoprotection in stable angina pectoris. However, in our experience,
      this beneficial anti-anginal effect is only observed in well-controlled
      situations.

PMID- 11286306
TI  - Cardiac energetics during ischaemia and the rationale for metabolic
      interventions.
AB  - Cardiac work is supported by high rates of combustion of carbon fuel and oxygen
      consumption. Fatty acids are the main fuel for the healthy heart, supplying
      approximately 60-80% of the energy. The balance of the energy comes from the
      oxidation of glucose and lactate. ATP is broken down to fuel contractile work.
      ATP is resynthesized in the mitochondria using energy from the oxidation of fatty
      acids, glucose, and lactate. Myocardial ischaemia dramatically alters fuel
      metabolism. Ischaemia occurs when the coronary blood flow is insufficient to
      supply enough oxygen to combust carbon fuels and resynthesize ATP at the normal
      rate. During partial reductions in coronary blood flow (30-60% of normal) there
      is a proportional decrease in the rates of oxygen consumption and production of
      ATP, and an increase in uptake of glucose by the heart. However, unlike under
      normal aerobic conditions, the glucose taken up by the ischaemic myocardium is
      not readily oxidized in the mitochondria, but rather is converted to lactate and
      there is a switch from uptake of lactate by the heart to lactate production. This
      causes a dramatic disruption in cell homeostasis: ATP content decreases; there is
      accumulation of lactate and H+, a fall in intracellular pH and a decrease in
      contractile work. Paradoxically, the ischaemic tissue continues to derive most of
      its energy (50-70%) from the oxidation of fatty acids despite there being a high
      rate of lactate production. This ischaemia-induced disruption of cardiac
      metabolism can be minimized by metabolic agents that decrease oxidation of fatty
      acids and increase the rates of combustion of glucose and lactate, resulting in
      clinical benefit to the ischaemic patient.

PMID- 11286307
TI  - Optimizing cardiac energy metabolism: how can fatty acid and carbohydrate
      metabolism be manipulated?
AB  - Optimizing energy metabolism in the heart is a novel approach for the management
      of ischaemic heart disease, especially in conjunction with optimizing or
      restoring coronary flow. In particular, promoting myocardial glucose metabolism
      can enhance heart function, lessen injury to tissue, or both. Several
      pharmacological agents that directly stimulate myocardial glucose oxidation or
      indirectly stimulate glucose oxidation secondary to inhibition of oxidation of
      fatty acids are now available. Trimetazidine is the first compound in the class
      of 3-ketoacyl-coenzyme A thiolase inhibitors to see wide-spread clinical use.
      This agent increases glucose metabolism in the heart secondary to a direct
      inhibition of fatty acid metabolism. Considering results of experimental and
      clinical studies on other agents, it is clear that metabolic agents may provide a
      new approach to treating cardiovascular disease that should complement and
      improve existing therapies.

PMID- 11286308
TI  - Acute coronary care and beyond: the expanding role of low-molecular-weight
      heparin.

PMID- 11286309
TI  - The low-molecular-weight heparin dalteparin as adjuvant therapy in acute
      myocardial infarction: the ASSENT PLUS study.
AB  - Rapid reperfusion of an infarct-related artery reduces the extent of myocardial
      damage and improves survival in acute myocardial infarction (AMI). Currently,
      anticoagulant treatment with unfractionated heparin (UFH) is used as adjuvant
      therapy to fibrinolytic treatment. The low-molecular-weight heparin (LMWH)
      dalteparin is at least as effective as UFH in unstable coronary artery disease.
      The ASSENT PLUS trial was carried out to evaluate whether dalteparin is as
      effective as UFH as an adjunct to recombinant tissue-plasminogen activator (rt
      PA) and aspirin in obtaining patency and Thrombolysis in Myocardial Infarction
      (TIMI)-3 flow in patients with AMI. The primary assessment of this phase II trial
      was TIMI flow, determined by coronary angiography. Patients with ST-elevation MI
      were randomized to receive aspirin and either rt-PA and UFH for 48 h, or rt-PA
      and dalteparin for 4 to 7 days. Evaluation was by TIMI flow after 4 to 7 days and
      clinical events (death, reinfarction, or revascularization) up to 30 days. There
      was a clear trend toward greater TIMI 3 flow with dalteparin compared with UFH.
      There was significantly less TIMI 0-1 flow or thrombus in the dalteparin group.
      Bleeding rates were similar. The occurrence of reinfarction was reduced during
      dalteparin treatment. These findings suggest that dalteparin could be substituted
      for UFH as an adjunct to rt-PA/aspirin in the management of patients with AMI.

PMID- 11286310
TI  - Atrial fibrillation: is there a role for low-molecular-weight heparin?
AB  - Atrial fibrillation (AF) is the most common form of tachyarrhythmia and carries a
      significant risk of serious thromboembolic complications. Anticoagulation is used
      for long-term thromboprophylaxis and for short-term management in a number of
      clinical situations, among which is the medical or electrical cardioversion of AF
      to sinus rhythm. Current guidelines recommend prompt cardioversion with heparin
      cover for AF of <48 h duration, and several weeks of warfarin therapy prior to
      cardioversion when the duration of disease is longer. Recent animal and human
      studies, however, have shown that swifter cardioversion is likely to be more
      successful in achieving sinus rhythm and in reducing the risk of recurrence of
      AF. Other observations have demonstrated that thrombi can develop within a few
      hours of the development of AF. These considerations suggest that cardioversion
      should be carried out as early as possible in all cases, and that the most
      sensitive means of detecting atrial thrombi, currently transesophageal
      echocardiography (TEE), should be used to screen all patients prior to
      cardioversion. Within this context, there is growing interest in the use of low
      molecular-weight heparin (LMWH) as an anticoagulant therapy in AF. Compared with
      unfractionated heparin, LMWH therapy does not involve prolonged intravenous
      administration, hospitalization, or laboratory monitoring; LMWH therefore has the
      potential to greatly simplify anticoagulation therapy for AF, especially
      pericardioversion. Recent studies have demonstrated that LMWH can be used safely
      and effectively in place of unfractionated heparin for acute treatment at the
      onset of AF and during early cardioversion. For example, in patients with AF, a
      strategy of immediate administration of dalteparin (100 IU/kg s.c. twice daily)
      continued for 11 days, combined with early TEE and immediate cardioversion in
      patients with no thrombus, resulted in sinus rhythm in 74% of patients after a
      median of 7 days. Low-molecular-weight heparin therapy may also find a role
      perioperatively and in selected patients, notably those with warfarin
      intolerance, as a replacement for warfarin following cardioversion. Controlled
      clinical studies are still required, however, to establish a firm, evidence-based
      foundation for the use of LMWHs in AF.

PMID- 11286311
TI  - Evaluating the place of low-molecular-weight heparin in the management of acute
      coronary syndromes. A panel discussion with audience participation.

PMID- 11286312
TI  - Improving outcomes in acute coronary syndromes--the FRISC II trial.
AB  - The FRISC II study addressed two key questions in the management of acute
      coronary syndromes: is it beneficial to extend low-molecular-weight heparin
      (LMWH) therapy with dalteparin beyond the initial period of acute treatment; and,
      is a strategy of early invasive therapy, including angioplasty and surgical
      revascularization, preferable to a more conservative strategy? The study focused
      on patients with unstable coronary artery disease (UCAD), that is, angina and non
      ST-segment-elevation myocardial infarction (MI). Patients were allocated in a
      randomized, factorial study design to either an invasive or a conservative
      management strategy. Within each of these groups, patients were further
      randomized to receive either 3 months of extended treatment with dalteparin or
      placebo, following at least 5 days' treatment with open-label dalteparin. After 1
      year, patient survival and MI-free survival were significantly higher in the
      invasive therapy group than in the noninvasive group. Patients who received
      extended dalteparin treatment had a significantly reduced probability of death or
      MI after 1 month (relative risk reduction 47%; p = 0.002), a benefit still
      evident after 60 days, but after 3 months there was no longer any significant
      clinical advantage compared with placebo. There was, however, a significant
      reduction in the combined incidence of death, MI, or revascularization at 3
      months in the extended dalteparin treatment group (relative risk reduction 13%; p
      = 0.031). The benefits of extended dalteparin treatment were particularly marked
      in patients with elevated troponin-T or ST-segment depression. A subgroup
      analysis of conservatively managed patients who underwent revascularization in
      the first 45 days revealed that the probability of death or MI at 1 year was
      significantly lower among patients who received extended dalteparin treatment
      (relative risk reduction 35%; p = 0.02). Extended dalteparin treatment is,
      however, associated with a small increase in bleeding risk. In conclusion, early
      invasive therapy (following combined treatment with aspirin and dalteparin) is
      recommended in a majority of patients with UCAD. Furthermore, extended dalteparin
      treatment for up to 45 days is efficacious and well tolerated, and therefore
      provides a useful "bridge" to revascularization when early revascularization is
      not immediately available.

PMID- 11286313
TI  - Glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparins: a combined
      role in coronary interventions?
AB  - Management strategies for acute coronary syndromes (ACS) are making increasing
      use of both low-molecular-weight heparins (LMWHs) and glycoprotein (GP) IIb/IIIa
      inhibitors. To date, however, relatively few studies have assessed the clinical
      potential of these two classes of agents in combination. There are theoretical
      grounds to expect LMWHs to be more effective than unfractionated heparin (UFH) in
      combination with GP IIb/IIIa inhibitors, since UFH, but not LMWH, activates
      platelets. The antiplatelet effects of GP IIb/IIIa inhibitors are therefore
      likely to be both more potent and more predictable when combined with LMWH. A
      recent study in more than 100 patients has demonstrated that a combination of
      dalteparin and the GP IIb/IIIa inhibitor abciximab provided effective
      anticoagulation in patients undergoing percutaneous coronary intervention (PCI),
      without causing significant bleeding or adverse events. Similar results were
      demonstrated in the National Investigators Collaborating on Enoxaparin (NICE-4)
      study using a combination of abciximab and enoxaparin in patients undergoing PCI.
      Of importance is the fact that there were no cases of severe thrombocytopenia in
      either LMWH study, although this is a recognized potential complication when UFH
      and abciximab are used in combination. Further studies are now warranted to
      confirm the efficacy of LMWH and GP IIb/IIIa inhibitors in combination, both for
      PCI and medical stabilization.

PMID- 11286314
TI  - Effect of denervation of the pylorus and transection of the duodenum on
      acetaminophen absorption in rats; possible mechanism for early delayed gastric
      emptying after pylorus preserving pancreatoduodenectomy.
AB  - Early delayed gastric emptying has been reported as a frequent complication
      following pylorus preserving pancreatoduodenectomy (PPPD). We investigated the
      effect of division of the pyloric branch of the vagus nerve and/or transection of
      the duodenum on gastric emptying using the acetaminophen method in rats to
      speculate the unknown etiology of early delayed gastric emptying after PPPD.
      Twenty-four male Wistar rats were divided into the following four groups; Group
      S, sham operation as controls; Group N, disturbance of neuro-vascular supply to
      the pylorus; Group D, temporary interference of the duodenal continuity; and
      Group N+D, with both procedures in Group N and Group D. Gastric emptying was
      measured using the acetaminophen method at 1, 2, and 4 weeks after operations in
      each group. No significant difference was observed in Group S at any intervals
      after the operation. Gastric emptying was prolonged significantly in Group N,
      Group D and Group N+D compared to Group S until 2 weeks following surgery.
      Significant delayed gastric emptying was sustained in Group N+D at 4 weeks,
      although gastric emptying in Group N and Group D was improved by 4 weeks. The
      results in rodent models suggest that both dissection of the pyloric branch of
      the vagus and transection of the duodenum might be causative factors of
      postoperative delayed gastric emptying following PPPD.

PMID- 11286315
TI  - Bladder preservation by internal iliac arterial infusion chemotherapy and
      irradiation in T3 bladder carcinoma patients over the age of 70 years.
AB  - Treatment by internal iliac arterial infusion chemotherapy (IA) combined with
      pelvic irradiation has proved to be effective for locally invasive bladder. Eight
      male patients, median age of 78 years (range 73-81) were enrolled. Pretreatment
      CT and whole layer core biopsy revealed T3a or T3b. Pelvic CT or fine needle
      aspiration biopsy following bipedal lymphography revealed N0 in 4 cases, N2 in 2
      and N3 in 2, respectively. Three to 7 cycles of cisplatin (CDDP) 30-50 mg/m2,
      methotrexate 20 mg/m2 and tetrahydropymnyl-adriamycin 20 mg/m2 every 3 week was
      administered combined with 40-50 Gy. of whole pelvis irradiation. In 4 renal
      function impaired patients, 100 mg/m2 of carboplatin was administered instead of
      CDDP. All patients obtained complete response and the bladders were preserved.
      Observation periods were from 9 to 75 months (median 37 months). One N2 patient
      died with metastatic disease and two died without carcinoma. Two patients
      developed invasive bladder cancer on the side opposite to the primary tumors.
      Both were successfully treated by IA and irradiation. Bladders of all except one
      patient functioned for a long period. Side effects of IA and irradiation were not
      significant. IA combined with pelvic irradiation is effective and safe for
      elderly patients with bladder carcinoma.

PMID- 11286317
TI  - Changes in fetal plasma adenosine and xanthine concentrations during fetal
      asphyxia with maternal oxygen administration in ewes.
AB  - In this study, we measured fetal plasma adenosine and xanthine concentrations
      during and after severe asphyxia, and investigated the key issues related to
      oxygen therapy. Asphyxia was induced by occluding the umbilical cord for 5
      minutes in 6 fetal sheep with and without the administration of oxygen to the
      ewe. Plasma adenosine concentration increased significantly during cord occlusion
      in the all fetuses, and the differences between the values in the fetuses with
      and without maternal oxygen administration was not significant. By 30 minutes
      after cord release, plasma adenosine concentration in all fetuses had returned to
      levels similar to those at the start of the experiment. Plasma xanthine
      concentration also increased during cord occlusion in all fetuses. However, 30
      minutes after cord release, plasma xanthine concentration had decreased
      significantly in fetuses without additional oxygen, while it did not change
      significantly in fetuses with maternal oxygen administration. Thus, we speculated
      that maternal oxygen administration before fetal asphyxia may not contribute to
      additional ATP stores in fetal organs and may produce oxygen free radicals
      following asphyxia.

PMID- 11286316
TI  - Expression of transcription factors during megakaryocytic differentiation of
      CD34+ cells from human cord blood induced by thrombopoietin.
AB  - Although normal megakaryocytic development has been shown to require the presence
      of functional GATA-1 and NF-E2 transcription factors in vivo, the roles of other
      members of the GATA binding factors and NF-E2 family during megakaryocytic
      differentiation are unclear. the present study, the expression of GATA family
      members, GATA-1 and GATA-2, a GATA-binding factor, EVI-1, the large subunit of NF
      E2 factor, p45 and the related factors, Nrf1, Nrf2, Nrf3, BACH1, BACH2, and the
      small subunit of NF-E2, MAFK and MAFG has been examined in human megakaryocytic
      and erythroid cells by reverse transcriptase-polymerase chain reaction. CD34+
      cells isolated from human cord blood were induced to unilineage megakaryocytic or
      erythroid differentiation in liquid suspension culture in the presense of
      thrombopoietin or erythropoietin, respectively. Each lineage was identified by
      monoclonal antibody against GPIIb/IIIa or glycophorin A. In megakaryocytic
      culture, p45, Nrf1, Nrf2, BACH1, MAFK and MAFG mRNAs were induced similarly to
      erythroid culture. Nrf3 mRNA was barely detected in both cultures. BACH2 was
      induced only in megakaryocytic culture, although the level of expression was low.
      Furthermore, the profiles of transcription factors involved in hematopoiesis, EVI
      1 and Ets-1 mRNAs were induced only in megakaryocytic culture. Megakaryocytic and
      erythroid differentiation pathways are closely related to each other, and these
      two lineage cells share a number of lineage-specific transcription factors.
      However, the results showed that the profile of the expression of these
      transcription factors in megakaryocytic cells is distinct from that of erythroid
      lineage. The dynamic changes in the levels of different transcription factors
      that occur during primary megakaryocytic differentiation suggest that the levels
      of these factors may influence the progression to specific hematopoietic
      pathways.

PMID- 11286318
TI  - Repeated electroconvulsive shock treatment induces two humoral anti-depressive
      factors in mouse.
AB  - Forced swimming is considered a depression model. Repeated electroconvulsive
      shock treatment shows an anti-depressive effect in mice forced swimming. In serum
      of the mice treated with repeated electroconvulsive shock, the humoral anti
      depressive factors were detected. The factors were the glycolipid having GalNAc
      alpha1-3GalNAc and mouse fibrinopeptide A having amino acid sequence
      TDTEKDGEFLSGGGV. The behavioral anti-depressive activity of the glycolipid was
      decreased by the low doses (100 to approximately 10 microg/kg) of dopamine 2
      receptor antagonist sulpiride. Behavioral activity of the peptide was also
      decreased by the low doses (100 to approximately 1 microg/kg) of dopamine 1
      receptor antagonist SCH-23390. The present findings clearly indicate that
      repeated electroconvulsive shock treatment induces the humoral anti-depressive
      factors affecting the dopaminergic neuronal system in mice.

PMID- 11286319
TI  - Retrospective study of factors affecting employability of individuals with
      cerebral palsy in Japan.
AB  - The purpose of this study was to investigate the characteristics of individuals
      with cerebral palsy that affected their ability to find a job in Japan. A
      retrospective nonrandomized descriptive study was performed. Subjects were 99
      individuals with cerebral palsy who were eligible to have a vocational training
      at the National Rehabilitation Center for the Disabled after graduation from high
      school. All of them were able to perform ADL unassistedly. The mean age of the
      subjects was 19.9 years (range, 18 to 33) and the mean intelligence quotient
      measured by WAIS-R was 78.5 (range, 46 to 110). Walking ability, being female and
      experience of learning in a regular middle high school were significant
      explanatory variables in the multiple regression equation. The ability of
      individuals with cerebral palsy to get a job in Japan in the 1990's was largely
      determined by being able to walk and having an education in a regular school.

PMID- 11286320
TI  - Oscillatory oxido-reductive reaction of intracellular hemoglobin in human
      erythrocyte incubated with o-aminophenol.
AB  - When human erythrocytes were incubated with o-aminophenol at pH 7.0 at 37 degrees
      C for 46 hours, intracellular oxyhemoglobin was completely oxidized to
      methemoglobin during the initial 6 hours, and methemoglobin formed was then
      reduced to oxyhemoglobin during the following 20 hours. This was demonstrated by
      the changes in absorption spectra of intracellular hemoglobin. Such oscillatory
      behavior of intracellular hemoglobin during reaction with o-aminophenol was
      explained by the fact that o-aminophenol has the ability to both oxidize
      oxyhemoglobin and reduce methemoglobin. In order to study the mechanism of oxido
      reductive reactions of hemoglobin with aromatic reductants including o
      aminophenol, the oxidation of ferrous hemoglobin and reduction of methemoglobin
      with various aromatic reductants such as o-aminophenol, 2-amino-4-methyl-phenol,
      2-amino-5-methylphenol, and homogentisic acid were investigated under various
      conditions. It was found that oxyhemoglobin was oxidized by these aromatic
      compounds, and the oxidation rate was accelerated in the presence of inositol
      hexaphosphate, but was not affected in the presence of catalase and superoxide
      dismutase, except for the case with homogentisic acid. The oxidation of ferrous
      hemoglobin by these compounds did not proceed under anaerobic conditions.
      Methemoglobin was reduced by these aromatic compounds, and the reduction rate was
      much accelerated in the presence of inositol hexaphosphate, but was not affected
      in the presence of catalase and superoxide dismutase, except for the case with
      homogentisic acid. The reduction of methemoglobin by these compounds proceeded
      under anaerobic conditions, suggesting that ferric heme of hemoglobin reacts
      directly with aromatic reductants. On the basis of these results, the mechanism
      of oxido-reductive reaction of ferrous and ferric hemoglobin with aromatic
      reductants was proposed.

PMID- 11286321
TI  - The development of the bradykinin agonist labradimil as a means to increase the
      permeability of the blood-brain barrier: from concept to clinical evaluation.
AB  - Labradimil (Cereport; also formerly referred to as RMP-7) is a 9-amino-acid
      peptide designed for selectivity for the bradykinin B2 receptor and a longer
      plasma half-life than bradykinin. It has been developed to increase the
      permeability of the blood-brain barrier (BBB) and is the first compound with
      selective bradykinin B2 receptor agonist properties to progress from concept
      design through to tests of efficacy in patients. In vitro studies demonstrate
      that labradimil has a longer half-life than bradykinin and selectively binds to
      bradykinin B2 receptors, initiating typical bradykinin-like second messenger
      systems, including increases in intracellular calcium and phosphatidylinositol
      turnover. Initial proof of principle studies using electron microscopy
      demonstrated that intravenous labradimil increases the permeability of the BBB by
      disengaging the tight junctions of the endothelial cells that comprise the BBB.
      Autoradiographic studies in rat models further demonstrated that labradimil
      increases the permeability of the BBB in gliomas. Intravenous or intra-arterial
      labradimil increases the uptake of many different radiolabelled tracers and
      chemotherapeutic agents into the tumour in a dose-related fashion. These effects
      are selective for the tumour and for the brain surrounding the tumour, and are
      particularly robust in tumour areas that are normally relatively impermeable. The
      increased chemotherapeutic concentrations are maintained for at least 90 minutes,
      well beyond the transient effects on the BBB. The increase in permeability with
      labradimil occurs rapidly but is transient, in that restoration of the BBB occurs
      very rapidly (2 to 5 minutes) following cessation of infusion. Even with
      continuous infusion of labradimil, spontaneous restoration of the barrier begins
      to occur within 10 to 20 minutes. Collectively, these data demonstrate that the
      B2 receptor system that modulates permeability of the BBB is highly sensitive and
      autoregulated and that careful attention to the timing of labradimil and the
      chemotherapeutic agent is important to achieve maximal effects. Survival studies
      in rodent models of both gliomas and metastatic tumours in the brain demonstrate
      that the enhanced uptake observed with the combination of labradimil and water
      soluble chemotherapeutics enhances survival to a greater extent than achieved
      with chemotherapy alone. Finally, preliminary clinical trials in patients with
      gliomas provide confirmatory evidence that labradimil permeabilises the blood
      brain tumour barrier and might, therefore, be used to increase delivery of agents
      such as carboplatin to tumours without the toxicity typically associated with
      dose escalation.

PMID- 11286322
TI  - A retrospective analysis of pharmacokinetic-pharmacodynamic parameters as
      indicators of the clinical efficacy of ceftizoxime.
AB  - OBJECTIVE: To analyse the relationship between a series of estimated
      pharmacokinetic-pharmacodynamic parameters and the reported efficacy of
      ceftizoxime. DESIGN: Retrospective literature search and analysis using different
      correlation models. METHODS: The following parameters were calculated for each
      group of patients included in the study from the simulated plasma concentration
      curves corresponding to the dosage regimen administered: (i) peak concentration
      at steady state divided by the minimum inhibitory concentration (CmaxSS/MIC);
      (ii) the time that the plasma drug concentration exceeded the MIC scaled to 24
      hours at steady state [(tSS)24h > MIC]; (iii) the total area under the
      concentration-time curve over 24 hours at steady state divided by the MIC
      [(AUC(SS))24h/MIC]; and (iv) the AUC at steady state for the period of time that
      the concentration is above the MIC over a period of 24 hours divided by the MIC
      [(AUIC(SS))24h]. A univariate correlation analysis was performed considering
      efficacy [rate (%) of clinical cure or bacterial eradication] as the dependent
      variable and the pharmacokinetic-pharmacodynamic parameter as the independent
      variable, using linear and nonlinear models. RESULTS: (tSS)24h > MIC was the only
      parameter that was statistically correlated with efficacy, the linear model being
      the best choice among the 4 relationship approaches tested. A biased frequency
      distribution of reported efficacy data constricts the correlation analysis to a
      narrow range of efficacy and hinders interpretation of the results. CONCLUSIONS:
      The reporting of cases with low efficacy rates as well as those with high
      efficacy rates, including information on patient idiosyncrasies and the infecting
      organisms, would be of great help in performing retrospective analyses of the use
      of antimicrobial agents, leading to the optimisation of therapy with this type of
      drug in clinical practice.

PMID- 11286323
TI  - Food does not influence the pharmacokinetics of a new extended release
      formulation of tolterodine for once daily treatment of patients with overactive
      bladder.
AB  - OBJECTIVE: To determine whether food intake influences the pharmacokinetics of a
      new, once daily, extended release (ER) capsule formulation of tolterodine in
      healthy volunteers, and to compare its bioavailability with that of the existing
      immediate release (IR) tablet. DESIGN: Open, randomised, 3-way crossover trial.
      PARTICIPANTS: 17 healthy volunteers (3 females, 14 males) aged between 19 and 50
      years. With the exception of 1 male volunteer, all participants were classified
      as extensive metabolisers by cytochrome P450 2D6 genotyping. METHODS: Volunteers
      received single oral doses of tolterodine L-tartrate ER 8 mg (2 x 4 mg capsules)
      on an empty stomach or with a standardised high-fat breakfast. Reference therapy
      comprised tolterodine L-tartrate IR 4 mg (2 x 2 mg tablets), administered in the
      fasting state. Serum concentrations of tolterodine, its active 5-hydroxymethyl
      metabolite (5-HM) and the active moiety (sum of unbound tolterodine + 5-HM) were
      measured for up to 72 hours post-dose. Safety endpoints were also determined.
      RESULTS: No effect of food on the bioavailability of tolterodine ER capsules was
      apparent and there was no sign of dose-dumping with meals. The geometric mean
      fed:fasting ratio of area under the serum concentration-time curve to infinity
      (AUCinfinity) of the active moiety, for all volunteers combined, was 0.95 (90%
      confidence interval 0.88 to 1.03). Equivalence with respect to AUCinfinity (dose
      corrected) was also found for the ER capsule compared with the IR tablet,
      although uncorrected maximum serum concentrations were around 50% lower despite
      the fact that the capsule dose was twice as high. Seven volunteers reported
      adverse events, predominantly headache. No volunteer reported dry mouth. Overall,
      there were no safety concerns. CONCLUSIONS: The new ER formulation of tolterodine
      shows no pharmacokinetic interaction with food. On the basis of these results,
      patients with overactive bladder may, therefore, be advised to take the drug
      without regard to the timing of meals, maximising convenience during therapy.

PMID- 11286324
TI  - Pharmacokinetic study of esomeprazole in the elderly.
AB  - OBJECTIVE: Esomeprazole is the first proton pump inhibitor to be developed as an
      optical isomer for the treatment of patients with acid-related diseases. The aim
      of this study was to examine the pharmacokinetics and tolerability of
      esomeprazole in the elderly, relative to middle-aged patients with gastro
      oesophageal reflux disease (GORD). DESIGN: Nonblinded single-centre
      pharmacokinetic study with historical control group. PATIENTS AND PARTICIPANTS:
      14 healthy elderly volunteers [mean age 74 (range 71 to 80) years]. METHODS:
      Participants received treatment with esomeprazole 40 mg once daily for 5 days,
      with 24-hour blood sampling on days 1 and 5. The total area under the plasma
      concentration-time curve (AUCinfinity), maximum plasma drug concentration (Cmax),
      terminal elimination half-life (t(1/2z)) and time to Cmax (tmax) were determined
      for the parent drug and its hydroxy and sulphone metabolites. AUCinfinity and
      Cmax data were compared with those in an historical group of 36 middle-aged
      patients [mean age 45 (range 29 to 58) years] with GORD, treated with an
      identical dosage of esomeprazole for 5 days. RESULTS: A total of 13 volunteers
      completed the study. On day 5, the mean plasma AUCinfinity of esomeprazole was
      16.0 micromol x h/L, Cmax was 5.6 micromol/L, tmax was 1.5 hours and t(1/2z) was
      1.7 hours. The AUCinfinity and Cmax values for the parent drug were 2- and 1.5
      fold higher on day 5 compared with day 1. AUCinfinity and Cmax values for the
      sulphone metabolite increased to a slightly greater extent, and values for the
      hydroxy metabolite were unchanged. Ratios of the AUCinfinity and Cmax values
      between elderly volunteers and patients with GORD were 1.25 [95% confidence
      interval (CI) 0.94, 1.67] and 1.18 (0.91, 1.52), respectively. Esomeprazole was
      well tolerated and there were no safety concerns. CONCLUSIONS: The AUCinfinity
      and Cmax values in the elderly were not significantly different from those
      obtained in a group of middle-aged patients. The difference for AUCinfinity was
      25% (95% CI -6% to +67%). Esomeprazole has a wide therapeutic window and our
      results do not indicate that dosage adjustment should be necessary in the
      elderly.

PMID- 11286325
TI  - Bioadhesion: new possibilities for drug administration?
AB  - Bioadhesion (and mucoadhesion) is the process whereby synthetic and natural
      macromolecules adhere to mucosal surfaces in the body. If these materials are
      then incorporated into pharmaceutical formulations, drug absorption by mucosal
      cells may be enhanced or the drug released at the site for an extended period of
      time. For synthetic polymers, such as the chitosans, carbopols and carbomers, the
      mechanism of bio/mucoadhesion is the result of a number of different
      physicochemical interactions. Biological bio/mucoadhesives, such as plant
      lectins, show specific interactions with cell surfaces and mucin and are seen as
      the 'second generation' bioadhesives. Bioadhesive systems for drug administration
      via the buccal and nasal cavities are nearing the market; in the case of nasal
      bioadhesion, bioadhesive microparticles are used. A bioadhesive formulation for
      drug administration to the vagina is in use. The gastrointestinal tract is
      proving a more difficult site because of the rapid turnover of mucus, and
      relatively constant transit time, but intensive research is in progress. Micro-
      and nano-particles, coated with either bio/mucoadhesive polymers or specific
      biological bioadhesives, are showing some promise, but will require considerable
      research and development before reaching the market.

PMID- 11286326
TI  - Clinical pharmacokinetics of capecitabine.
AB  - Capecitabine is a novel oral fluoropyrimidine carbamate that is preferentially
      converted to the cytotoxic moiety fluorouracil (5-fluorouracil; 5-FU) in target
      tumour tissue through a series of 3 metabolic steps. After oral administration of
      1250 mg/m2, capecitabine is rapidly and extensively absorbed from the
      gastrointestinal tract [with a time to reach peak concentration (tmax) of 2 hours
      and peak plasma drug concentration (Cmax) of 3 to 4 mg/L] and has a relatively
      short elimination half-life (t(1/2)) [0.55 to 0.89 h]. Recovery of drug-related
      material in urine and faeces is nearly 100%. Plasma concentrations of the
      cytotoxic moiety fluorouracil are very low [with a Cmax of 0.22 to 0.31 mg/L and
      area under the concentration-time curve (AUC) of 0.461 to 0.698 mg x h/L]. The
      apparent t(1/2) of fluorouracil after capecitabine administration is similar to
      that of the parent compound. Comparison of fluorouracil concentrations in primary
      colorectal tumour and adjacent healthy tissues after capecitabine administration
      demonstrates that capecitabine is preferentially activated to fluorouracil in
      colorectal tumour, with the average concentration of fluorouracil being 3.2-fold
      higher than in adjacent healthy tissue (p = 0.002). This tissue concentration
      differential does not hold for liver metastasis, although concentrations of
      fluorouracil in liver metastases are sufficient for antitumour activity to occur.
      The tumour-preferential activation of capecitabine to fluorouracil is explained
      by tissue differences in the activity of cytidine deaminase and thymidine
      phosphorylase, key enzymes in the conversion process. As with other cytotoxic
      drugs, the interpatient variability of the pharmacokinetic parameters of
      capecitabine and its metabolites, 5'-deoxy-5-fluorocytidine and fluorouracil, is
      high (27 to 89%) and is likely to be primarily due to variability in the activity
      of the enzymes involved in capecitabine metabolism. Capecitabine and the
      fluorouracil precursors 5'-deoxy-5-fluorocytidine and 5'-deoxy-5-fluorouridine do
      not accumulate significantly in plasma after repeated administration. Plasma
      concentrations of fluorouracil increase by 10 to 60% during long term
      administration, but this time-dependency is assumed to be not clinically
      relevant. A potential drug interaction of capecitabine with warfarin has been
      observed. There is no evidence of pharmacokinetic interactions between
      capecitabine and leucovorin, docetaxel or paclitaxel.

PMID- 11286327
TI  - Electrode potential-modulated cleavage of surface-confined DNA by hydroxyl
      radicals detected by an electrochemical biosensor.
AB  - Damage to DNA frequently involves interruption of DNA sugar-phosphate strands
      (strand breaks, sb). Under aerobic conditions, transition metal ions cause DNA
      damage through production of reactive oxygen species (frequently via Fenton-type
      reactions). Formation of sb in covalently closed supercoiled (sc) DNA can be
      detected using an electrochemical biosensor based on a scDNA-modified mercury
      electrode. By controlling the potential of the electrode, this technique can be
      employed in studies of redox reactions involved in formation of DNA strand
      breaks, and to detect species involved in these reactions. ScDNA anchored at HMDE
      was cleaved by catalytic amounts of iron/EDTA ions in the absence of chemical
      reductants when appropriate electrode potential (sufficiently negative to reduce
      [Fe(EDTA)]- to [Fe(EDTA)]2-) was applied. The process required oxygen or hydrogen
      peroxide. The extent of DNA damage increased with the shift of the electrode
      potential to negative values, displaying a sharp inflection point matching the
      potential of [Fe(EDTA)]2-/[Fe(EDTA)]- redox pair. In the absence of transition
      metal ions, significant DNA damage was observed at potentials sufficiently
      negative for reduction of dioxygen at the mercury electrode. This observation
      suggests cleavage of the surface-attached scDNA by radical intermediates of
      oxygen reduction at HMDE.

PMID- 11286328
TI  - Non-invasive measurement of cell membrane associated proton gradients by ion
      sensitive field effect transistor arrays for microphysiological and
      bioelectronical applications.
AB  - The pH in the cellular microenvironment (pH(M)) is an important regulator of cell
      to-cell and cell-to-host interactions. Additionally the extracellular
      acidification rate of a cell culture is an important indicator of global cellular
      metabolism. In a new approach a biocompatible ion-sensitive field effect
      transistor (ISFET)-array was developed to measure the pH(M) close to a surface
      and the global extracellular acidification rate at the same time. This ISFET
      array is part of a new multiparametric microsensor chip. The paper highlights
      some basic applications of this method for in-vitro measurements. Using a fluid
      perfusion system for cell culture media, it is possible to measure the pH(M) of
      few (five to ten) adherent tumor cells in a distance of 10-100 nm from the cell
      plasma membrane. Experiments showed a pH(M)-value of 6.68 +/- 0.06 pH. Further
      experiments suggest that both the low pH, and the extracellular acidification
      rate of the examined tumor cell line are mainly built up by glycolysis.

PMID- 11286329
TI  - Chemiluminescent choline biosensor using histidine-modified peroxidase
      immobilised on metal-chelate substituted beads and choline oxidase immobilised on
      anion-exchanger beads co-entrapped in a photocrosslinkable polymer.
AB  - A novel sensing layer design is presented based on the non-covalent
      immobilisation of enzymes on derivatized Sepharose beads subsequently entrapped
      in PVA-SbQ photopolymer. Two different modified Sepharose beads were used, IDA-
      and DEAE-Sepharose, for the immobilisation, respectively, of horseradish
      peroxidase (HRP) modified with histidine, and choline oxidase (Chx). The HRP-IDA
      Sepharose-based sensing layer was used in a flow injection analysis
      chemiluminescent system as the basis of an H2O2 biosensor. It was shown that the
      pre-immobilisation on IDA-Sepharose beads enhanced the sensing layer stability
      and enabled the immobilisation of a larger amount of enzyme. A 1.8 mg charge of
      HRP-IDA-Sepharose beads in the sensing layer produced the most sensitive H2O2
      biosensor. Such an analytical system exhibited very good performances, with a
      cycle time of 2 min and a detection limit of 15 pmol (detection ranging over four
      decades at least), and an unusual long operational stability of 200 measurements
      (CV, 3.5%). The HRP-IDA-Sepharose beads were then combined with Chx-DEAE
      Sepharose. With this modified Sepharose-based biosensor the limit of detection
      for choline (S/N, 3) was equal to 0.5 pmol and the working range was 0.35 pmol-10
      nmol. Moreover, the cycle time was only 2.5 min with the new sensing layer, and a
      long operational stability of 150 successive assays was found, with a variation
      coefficient of 2.6%.

PMID- 11286330
TI  - Rapid and sensitive biosensor for Salmonella.
AB  - The rapid and sensitive detection of Salmonella typhymurium based on the use of a
      polyclonal antibody immobilized by the Langmuir-Blodgett method on the surface of
      a quartz crystal acoustic wave device was demonstrated. The binding of bacteria
      to the surface changed the crystal resonance parameters; these were quantified by
      the output voltage of the sensor instrumentation. The sensor had a lower
      detection limit of a few hundred cells/ml, and a response time of < 100 s over
      the range of 10(2)-10(10) cells/ml. The sensor response was linear between
      bacterial concentrations of 10(2)-10(7) cells/ml, with a sensitivity of 18
      mV/decade. The binding of bacteria was specific with two binding sites needed to
      bind a single cell. The sensors preserve approximately 75% of their sensitivity
      over a period of 32 days.

PMID- 11286331
TI  - Amperometric glucose biosensor based on lipid film.
AB  - A novel glucose biosensor based on cast lipid film was developed. This model of
      biological membrane was used to supply a biological environment on the surface of
      the electrode, moreover it could greatly reduce the interference and effectively
      exclude hydrophilic electroactive material from reaching the detecting surface.
      TTF was selected as a mediator because of its high electron-transfer efficiency,
      and it was incorporated in the lipid film firmly. Glucose oxidase was immobilized
      in hydrogel covered on the lipid film. The effects of pH, operating potential
      were explored for the optimum analytical performance by using amperometric
      method. The response time of the biosensor was less than 20 s, and the linear
      range is up to 10 mmol l(-1) (corr. coeff. 0.9932) with the detection limit of 2
      x 10(-5) mol l(-1). The biosensor also exihibited good stability and
      reproducibility.

PMID- 11286332
TI  - Cytosensor Microphysiometer: technology and recent applications.
AB  - The Cytosensor Microphysiometer system detects functional responses from living
      cells in minutes and offers novel information on cell signalling that is often
      unobtainable with other assay methods. The principle of the system is based on
      the measurement of small changes in extracellular acidification, using a light
      addressable potentiometric sensor (LAPS). Energy metabolism in living cells is
      tightly coupled to cellular ATP usage, so that any event which perturbs cellular
      ATP levels--such as receptor activation and initiation of signal transduction-
      will result in a change in acid excretion. As the extrusion of protons is a very
      general parameter involved in the activation of nearly all kinds of membrane
      bound receptors, receptors can be investigated without prior knowledge of the
      corresponding signalling pathway. However, by blocking certain signalling
      pathways inside the cell by means of signal transduction probes, specificity can
      be brought into the system and the corresponding receptor pathways can easily be
      elucidated. The aim is to give an overview about Cytosensor Microphysiometer
      technology and to demonstrate, with the help of some recent applications, the
      capability of the system to measure acidification rates from a wide variety of
      cell- and receptor-types coupled to different signal transduction pathways. This
      feature makes the cytosensor system an ideal tool for acting as a single assay
      system and circumventing the need for multiple assays.

PMID- 11286333
TI  - Comparative assessment of chemical and gamma-irradiation procedures for
      implantable glucose enzyme electrodes.
AB  - Chemical and gamma-irradiation sterilisation were examined in this study for
      implantable needle electrodes. Exposure to isopropyl alcohol (IPA) led to
      response elevation, but time-dependent exposures up to 30 min variously to
      chlorhexidine, H2O2, HCl, HCl/IPA, and alcoholic iodine/potassium iodide, all
      caused substantial time-dependent response degradation. Sterility was not
      assessed for such electrodes. High dose (30 KGy) gamma-irradiation also
      compromised sensor response, with exposed electrodes exhibiting approximately 30%
      reduction in response, comparable in magnitude to 10 min exposure to chemical
      sterilisation. However, a lower dose (25 KGy) gamma-irradiation was well
      tolerated and subsequent microbiological testing (following contamination with
      Streptococcus epidermidis and Staphylococus aureus) proved device sterility with
      no culture growth following 7 days incubation at 37 degrees C in brain heart
      infusion medium.

PMID- 11286334
TI  - Operational characteristics of an antibody-immobilized QCM system detecting
      Salmonella spp.
AB  - A quartz crystal microbalance (QCM) system detecting Salmonella spp. was
      developed by an anti-Salmonella antibody immobilization onto one gold surface of
      a piezoelectric quartz crystal surface with sulfosuccinimidyl 6-[3-(2
      pyridyldithio)propionamido]hexanoate (sulfo-LC-SPDP) thiolation. The optimum
      temperature and pH for the antibody-immobilized sensor were 35 degrees C and 7.2,
      respectively. The frequency shifts obtained were correlated with the Salmonella
      concentrations in the range 3.2 x 10(6)-4.8 x 10(8) CFU per ml. The system was
      quite specific to Salmonella spp. and applicable for repetitive use after a
      regeneration step employing 1.2 M NaOH. A model sample measurement was done for a
      market milk spiked with Salmonella typhimurium.

PMID- 11286335
TI  - Evaluation of agonist selectivity for the NMDA receptor ion channel in bilayer
      lipid membranes based on integrated single-channel currents.
AB  - A new method for evaluating chemical selectivity of agonists to activate the N
      methyl-D-aspartate (NMDA) receptor was presented by using typical agonists NMDA,
      L-glutamate and (2S, 3R, 4S)-2-(carboxycyclopropyl)glycine (L-CCG-IV) and the
      mouse epsilon1/zeta1 NMDA receptor incorporated in bilayer lipid membranes (BLMs)
      as an illustrative example. The method was based on the magnitude of an agonist
      induced integrated single-channel current corresponding to the number of total
      ions passed through the open channel. The very magnitudes of the integrated
      single-channel currents were compared with the different BLMs as a new measure of
      agonist selectivity. The epsilon1/zeta1 NMDA receptor was partially purified from
      Chinese hamster ovary (CHO) cells expressing the epsilon1/zeta1 NMDA receptor and
      incorporated in BLMs formed by the tip-dip method. The agonist-induced integrated
      single-channel currents were obtained at 50 microM agonist concentration, where
      the integrated current for NMDA was shown to reach its saturated value. The
      obtained integrated currents were found to be (4.5 +/- 0.55) x 10(-13) C/s for
      NMDA, (5.8 +/- 0.72) x 10(-13) C/s for L-glutamate and (6.6 +/- 0.61) x 10(-13)
      C/s for L-CCG-IV, respectively. These results suggest that the agonist
      selectivity in terms of the total ion flux through the single epsilon1/zeta1 NMDA
      receptor is in the order of L-CCG-IV approximately = L-glutamate > NMDA.

PMID- 11286336
TI  - Nature of immobilized antibody layers linked to thioctic acid treated gold
      surfaces.
AB  - Utilization of 125I-labeled IgG enables an investigation of protein immobilized
      to gold electrodes sputter deposited on microporous nylon membranes, including
      the precise nature of the surface-protein bond (i.e. covalent or non-specific
      adsorption), physical location of the immobilized protein (i.e. on the surface of
      the gold electrode or within the pores of the membrane), and the amount of
      protein immobilized. This is accomplished by comparing the mass of protein
      immobilized to gold surfaces that have been treated in several different
      fashions, as well as, deposition of the gold on nylon membranes that have been
      treated differently. It is shown that these microporous gold electrodes, proposed
      previously for conducting novel non-separation electrochemical enzyme
      immunoassays, consist of multiple protein layers non-specifically adsorbed.
      Approximately, half of the total adsorbed protein is immobilized to the gold
      surface with the remaining protein bound within the pores on the nylon membrane.

PMID- 11286337
TI  - Improved multianalyte detection of organophosphates and carbamates with
      disposable multielectrode biosensors using recombinant mutants of Drosophila
      acetylcholinesterase and artificial neural networks.
AB  - Engineered variants of Drosophila melanogaster acetylcholinesterase (AChE) were
      used as biological receptors of AChE-multisensors for the simultaneous detection
      and discrimination of binary mixtures of cholinesterase-inhibiting insecticides.
      The system was based on a combination of amperometric multielectrode biosensors
      with chemometric data analysis of sensor outputs using artificial neural networks
      (ANN). The multisensors were fully manufactured by screen-printing, including
      enzyme immobilisation. Two types of multisensors were produced that consisted of
      four AChE variants each. The AChE mutants were selected in order to obtain high
      resolution, enhanced sensitivity and minimal assay time. This task was
      successfully achieved using multisensor I equipped with wild-type Drosophila AChE
      and mutants Y408F, F368L, and F368H. Each of the AChE variants was selected on
      the basis of displaying an individual sensitivity pattern towards the target
      analytes. For multisensor II, the inclusion of F368W, which had an extremely
      diminished paraoxon sensitivity, increased the sensor's capacity even further.
      Multisensors I and II were both used for inhibition analysis of binary paraoxon
      and carbofuran mixtures in a concentration range 0-5 microg/l, followed by data
      analysis using feed-forward ANN. The two analytes were determined with prediction
      errors of 0.4 microg/l for paraoxon and 0.5 microg/l for carbofuran. A complete
      biosensor assay and subsequent ANN evaluation was completed within 40 min. In
      addition, multisensor II was also investigated for analyte discrimination in real
      water samples. Finally, the properties of the multisensors were confirmed by
      simultaneous detection of binary organophosphate mixtures. Malaoxon and paraoxon
      in composite solutions of 0-5 microg/l were discriminated with predication errors
      of 0.9 and 1.6 microg/l, respectively.

PMID- 11286338
TI  - Porous gold surfaces for biosensor applications.
AB  - The sensitivity of optical biosensors where the detection takes place on a planar
      gold surface can be improved by making the surface porous. The porosity allows a
      larger number of ligands per surface area resulting in larger optical shifts when
      interacting with specifically binding analyte molecules. The porous gold was
      deposited as a thin layer on a planar gold surface by electrochemical deposition
      in a solution of tetrachloroaurate and lead acetate. A protein, streptavidin, was
      adsorbed into the formed porous layer and the time course of the adsorption was
      monitored by in-situ ellipsometry. When the porous layer was 500 nm in thickness
      a six-fold increase of the ellipsometric response was obtained compared with a
      planar gold surface. The dependency of porosity and layer thickness was explained
      with a mathematical model of the gold/porous gold/protein/solution system.

PMID- 11286339
TI  - Amperometric measurement of copper ions with a deputy substrate using a novel
      Saccharomyces cerevisiae sensor.
AB  - The first microbial biosensor to detect Cu2+ by an amperometric method has been
      developed. For this purpose, recombinant Saccharomyces cerevisiae strains are
      suitable as the microbial component. These strains contain plasmids with the Cu2+
      inducible promoter of the CUP1-gene from Saccharomyces cerevisiae fused to the
      lacZ-gene from E. coli. On this sensor the CUP1 promoter is first induced by the
      Cu2+-containing probe and subsequently lactose is used as a deputy substrate to
      make the measurement. If Cu2+ is present in the sample, these recombinant strains
      are able to utilize lactose as a carbon source, which leads to alterations in the
      oxygen consumption of the cells. The sensor measured Cu2+ in a concentration
      range between 0.5 and 2 mM CuSO4. In addition, an indirect amperometric
      measurement principle was developed which allows the detection of samples
      containing Cu2+ and fast biodegradable substances.

PMID- 11286341
TI  - Sleep research: celebration and opportunity.

PMID- 11286340
TI  - Development of immunosensors for the analysis of 1-naphthol in organic media.
AB  - Immunosensor systems have been developed for the rapid determination of 1
      naphthol. In this work, the comparison of performance of immunosensors working in
      aqueous and organic media was done. Direct, indirect and capture formats were
      studied. Immunoreagents were immobilized on controlled pore glass (CPG),
      hidroxysuccinimide agarose gel or on azlactone Protein A/G supports. The Protein
      A/G-based sensor showed the best performance. In aqueous media, a LOD of 16.2
      microg l(-1) and a DR of 33.7-586.6 microg l(-1) were achieved employing Tween 20
      at a concentration ranging from 0.01 to 0.05% v/v. Maximum sensitivity was
      reached with 0.025% of surfactant. Binary mixtures of methanol or acetonitrile
      with aqueous buffer and ternary mixtures of methanol/isopropanol or ethyl
      acetate/methanol with the same buffer were studied as organic media. The mixture
      50% MeOH-50% 20 mM sodium phosphate, pH 8, with 0.05% (v/v) Tween 20 resulted to
      be the best. A detection limit of 12.0 microg l(-1) and a dynamic range of 53.6
      17,756.0 microg l(-1) were reached. The recycling of Protein A/G-based sensor
      working in this media was about 300 assays. Preconcentration factors around 250
      were achieved using methanol as extracting solvent. It has been demonstrated that
      the technique can be successful in carrying out the analysis of low solubility in
      water analytes, such as 1-naphthol. The sensors developed can use higher
      concentrations of organic solvent (up to 50% methanol) compared to ELISA. On the
      other hand, the advantage of preconcentration can also be taken for the use of
      the same procedure as recommended for standard sample treatments.

PMID- 11286342
TI  - Suppression of diaphragmatic activity during spontaneous ponto-geniculo-occipital
      waves in cat.
AB  - It has been reported that spontaneous ponto-geniculo-occipital (PGO) waves, which
      occur during REM sleep in the cat, are associated with a brief inhibition of
      diaphragmatic activity (Orem, 1980). This report was preliminary and not
      supported by a detailed analysis. We report here analysis of the relationship
      between PGO waves and diaphragmatic activity based on 3073 PGO waves recorded
      simultaneously with diaphragmatic activity. The results show that there is indeed
      an inhibition of diaphragmatic activity during PGO waves. This inhibition has an
      amplitude up to 20% of background, and a duration (approximately 80 ms)
      approximately coinciding with the temporal duration of the PGO wave. In addition,
      we analyzed the relationships among the activity of medullary respiratory
      neurons, PGO waves, and diaphragmatic activity. Two neurons were observed whose
      relationships to diaphragmatic activity and PGO waves were consistent with the
      idea that they mediated the PGO-associated inhibition of diaphragmatic activity.
      However, the number of PGO waves involved in the analysis of the interaction
      between medullary respiratory neuronal activity and diaphragmatic activity was
      small and, although suggestive, was not conclusive.

PMID- 11286343
TI  - Cholinomimetics, but not morphine, increase antinociceptive behavior from pontine
      reticular regions regulating rapid-eye-movement sleep.
AB  - Sleep disruption is a significant problem associated with the subjective
      experience of pain. Both rapid-eye-movement (REM) sleep and nociception are
      modulated by cholinergic neurotransmission, and this study tested the hypothesis
      that antinociceptive behavior can be evoked cholinergically from medial pontine
      reticular formation (mPRF) regions known to regulate REM sleep. The foregoing
      hypothesis was investigated by quantifying the effect of mPRF drug administration
      on tail flick latency (TFL) of cat during polygraphically defined sleep/wake
      states. The mPRF was microinjected with 0.25 ml saline, carbachol (4.0 microg),
      neostigmine (6.7 microg), or morphine sulfate (14.7 microg), and TFL measures
      were obtained in response to radiant heat. During wakefulness TFL (% increase)
      was not increased by morphine or saline, but was significantly increased by mPRF
      administration of carbachol (42.4%) and neostigmine (35.2%). Cortical
      somatosensory potentials (SSEPs) were reliably evoked by tail stimulation before
      and after mPRF microinjections of carbachol. The results show for the first time
      that mPRF administration of cholinomimetics significantly increased TFL. During
      NREM sleep and REM sleep, TFL was significantly increased compared to waking TFL
      (110% and 321%, respectively). The finding of sleep-dependent alterations in TFL
      demonstrates that mPRF regions known to regulate REM sleep can modulate
      supraspinal cholinergic antinociceptive behavior.

PMID- 11286344
TI  - Effects of aging on sleep in the golden hamster.
AB  - The golden hamster (Mesocricetus auratus) has been a model organism for the study
      of circadian rhythmicity and, in particular, the effects of age on the circadian
      system. Surprisingly, nothing is known about the effects of advanced age on sleep
      in this species. As a first step in determining the effects of aging on sleep in
      the golden hamster, we recorded sleep for 24 hours in 12 young (3 months) and 18
      old (17-18 months) golden hamsters entrained to a 14:10 light:dark (LD) cycle.
      Aged hamsters exhibited small but significant increases in overall NREM sleep
      time, primarily due to an increase in time the old animals spent in the NREM
      sleep state during the dark period relative to the young hamsters. There were no
      significant differences in REM sleep, median sleep episode length, or the number
      of arousals. The most striking differences between the sleep of young and old
      hamsters was in NREM delta (0.5-4 Hz) power per epoch. Old hamsters showed
      approximately 27% less (p=0.0004) delta power per NREM epoch than young hamsters.
      It is possible that increased NREM sleep time in the old hamsters may be a failed
      attempt to maintain cumulative delta power; ie, old hamsters may have more NREM
      sleep in order to make up for the lower intensity of their sleep. This decline in
      delta power with age parallels earlier findings in cats and humans, although has
      it not been previously reported in rodents.

PMID- 11286345
TI  - Inactivation of the pons blocks medullary-induced muscle tone suppression in the
      decerebrate cat.
AB  - The pontomedullary region is responsible for the reduction of muscle activity in
      rapid-eye-movement sleep and contributes to the control of muscle tone in waking.
      This study sought to clarify the nature of the interaction between the pontine
      and medullary reticular formation in mediating muscle tone suppression. The
      degree of medullary-induced neck muscle tone suppression in the decerebrate cat
      was assessed before and after microinjection of lidocaine into the pontine
      reticular formation. Medullary stimulation-induced suppression of neck muscle
      tone was blocked after pontine lidocaine microinjection. The maximum blockade was
      observed at 16.6 minutes on average after the injection, and recovery occurred
      within 45 minutes. We conclude that descending mechanisms from the medulla are
      not sufficient for the triggering of muscle tone suppression. A two-way
      interaction between the medulla and pons is hypothesized to play a crucial role
      in the control of muscle tone.

PMID- 11286346
TI  - Sleep-disordered breathing and self-reported general health status in the
      Wisconsin Sleep Cohort Study.
AB  - OBJECTIVE: To determine the relationship between sleep-disordered breathing and
      self-reported general health status. breathing status assessed by overnight in
      laboratory polysomnography. SETTING: General Community. SUBJECTS: Employed men
      (n=421) and women (n=316), ages 30-60 years, enrolled in the Wisconsin Sleep
      Cohort Study. INTERVENTIONS: None. OUTCOME MEASURE: Self-reported general health
      profile and life satisfaction measured by the Medical Outcomes Survey Short Form
      36 and obtained by interview. RESULTS: Sleep-disordered breathing was associated
      with lower general health status before and after adjustment for age, sex, body
      mass index, smoking status, alcohol usage, and a history of cardiovascular
      conditions. Even mild sleep-disordered breathing (apnea-hypopnea index = 5) was
      associated with decrements in the Medical Outcomes Short Form 36 Survey health
      constructs comparable to the magnitude of decrements linked to other chronic
      conditions such as arthritis, angina, hypertension, diabetes, and back problems.
      CONCLUSIONS: Sleep-disordered breathing is independently related to lower general
      health status, and this relationship is of clinical significance. Given the
      growing emphasis of the importance of patients' perceptions of health, these
      findings are relevant to estimating the overall impact of sleep-disordered
      breathing.

PMID- 11286347
TI  - Long-term facilitation of ventilation in humans during NREM sleep.
AB  - The purpose of this study was to determine whether episodic hypoxic exposure
      would elicit long term facilitation (LTF) of ventilation (V(I)) in sleeping
      humans. Twenty subjects gave written informed consent. Of these, six subjects
      were unable to maintain stable stage 2 sleep or deeper for a majority of the
      experiment and their data were excluded from the analysis. On night 1 after
      subjects had reached stable sleep (stage 2 or deeper), the subjects breathed room
      air for 5 minutes, followed by 3 minutes of hypoxia (F(I)O2 = 8%). This sequence
      was repeated 10 times, and the breathing pattern was observed for a further 60
      minutes. Subjects returned to the laboratory for a second visit, which served as
      a sham night. Instrumentation and study time were the same as on night 1, but
      subjects breathed room air only. Airflow, tidal volume (V(T)), end tidal O2 and
      CO2, and estimation of arterial O2 saturation (%) were measured. Seven of the
      subjects had long-term facilitation (LTF), which was manifested as a significant
      increase in V(I) that persisted for up to 40 minutes following the last hypoxic
      exposure. In the other seven subjects, no substantial increase in V(I) was found.
      We could not explain this difference based on body size (BMI), gender, level of
      hypoxemia, or magnitude of the hyperpnea during hypoxia. The difference between
      the two groups was that the LTF group consisted of habitual snorers, and that the
      NLTF were not inspiratory-flow-limited during the experiment.

PMID- 11286348
TI  - Local reflex mechanisms: influence on basal genioglossal muscle activation in
      normal subjects.
AB  - STUDY OBJECTIVES: To define the influence of topical nasopharyngeal anesthesia on
      genioglossal EMG responsiveness to both negative pressure and basal muscle
      activity. The effects on airway mechanics (resistance and collapsibility) were
      also determined. PARTICIPANTS: 18 normal adult subjects (9 males and 9
      premenopausal females) DESIGN AND MEASUREMENTS: Genioglossal EMG (GG EMG) was
      measured with intramuscular electrodes. Basal phasic and tonic GG EMG were
      defined, in addition to the muscle response to multiple brief applications of
      negative airway pressure (-10 to 12 cm H2O). Airflow resistance (at 0.2 L/second
      and peak flow) plus airway collapsibility were also determined. All measurements
      were completed with and without dense nasopharyngeal anesthesia (lidocaine).
      RESULTS: Following nasopharyngeal anesthesia, peak GG EMG response to negative
      pressure fell from 28.1+/-4.3 (SE) to 19.6+/-3.4% of maximum (p<0.01). This was
      associated with a significant fall in both peak phasic and tonic GG EMG under
      basal conditions (phasic: 20.2+/-3.2 to 15.9+/-2.7% of maximum, tonic: 13.9+/-2.5
      to 9.8+/-1.8% of maximum). Falling muscle activity led to a trend of rising
      airflow resistance and increasing airway collapsibility. CONCLUSIONS: Local,
      topical receptor mechanisms located in the nasopharynx importantly modulate upper
      airway dilator muscle activity in humans during normal tidal breathing.
      Therefore, the mechanisms exist for the airway to respond to local events which
      would tend to compromise airway patency.

PMID- 11286349
TI  - The effects of hypoxia and sleep apnea on isoproterenol sensitivity.
AB  - STUDY OBJECTIVES: To determine the effects of both apnea and hypoxia on beta
      adrenergic receptor sensitivity. DESIGN: Cross-sectional study. SETTING: A
      clinical research center. PATIENTS: Forty-five normotensive and hypertensive
      sleep apnea patients (respiratory disturbance index >20) and non-apneic controls.
      MEASUREMENTS AND RESULTS: The chronotropic 25 dose (CD25), an in vivo measure of
      beta-adrenergic receptor sensitivity derived from the heart rate response to a
      graded infusion of isoproterenol, was determined while subjects breathed either a
      normoxic (21% O2, 79% N2) or a hypoxic (15% O2, 85% N2) gas mixture. Under
      normoxic conditions, apnea patients showed a significantly higher CD25 (lower
      beta-adrenergic receptor sensitivity) as compared to controls (5.9 microg, SD=2.1
      versus 4.6 microg, SD=1.2, respectively; p=0.018). In response to hypoxia, apnea
      patients showed no change in CD25, while controls showed a significant increase
      in CD25 (beta-adrenergic receptor desensitization) (p=0.002), to a value
      comparable to the apneics' (5.6 microg, SD=2.0). CONCLUSION: The in vivo finding
      of reduced beta-adrenergic receptor sensitivity in sleep apnea patients is
      consistent with previous in vitro assessments of the beta-adrenergic receptor.
      The finding that apnea patients do not respond to hypoxia with a further receptor
      desensitization suggests that sleep apnea patients may have reached a threshold
      effect of hypoxia on the beta-adrenergic receptor. These findings may be relevant
      to the greater incidence of hypertension seen in patients with sleep apnea
      syndrome.

PMID- 11286350
TI  - Blood pressure perturbations caused by subclinical sleep-disordered breathing.
AB  - We studied the acute effects of apneas and hypopneas on blood pressure in a
      nonclinic population of middle-aged adults. Arterial pressure was measured
      noninvasively (photoelectric plethysmography) during an overnight, in-laboratory
      polysomnographic study in 72 men and 23 women enrolled in the Wisconsin Sleep
      Cohort Study, a population-based study of sleep-disordered breathing. Sleep
      disordered breathing events (272 apneas and 1469 hypopneas) were observed in 92%
      of subjects. The across-subject mean decreases in arterial O2 saturation were 9+/
      8% (SD) for apneas (17+/-8 seconds duration) and 4+/-3% for hypopneas (21+/-6
      seconds duration; 41+/-17% of baseline ventilation). In both apneas and
      hypopneas, even those with only 1% to 3% O2 desaturations, blood pressure
      decreased during the event, followed by an abrupt increase in the postevent
      recovery period. Mean values for peak changes in blood pressure (difference
      between the maximum during the recovery period and the minimum during the event)
      were 23+/-10 mm Hg for systolic and 13+/-6 mm Hg for diastolic pressure. The
      strongest predictors of the pressor responses to apneas and hypopneas were (in
      order of importance): magnitude of the ventilatory overshoot, length of the
      event, magnitude of changes in heart rate and arterial O2 saturation, and
      presence or absence of electroencephalographic arousal. We speculate that these
      fluctuations may play a role in the pathogenesis of hypertension in individuals
      with subclinical sleep-disordered breathing.

PMID- 11286351
TI  - Reliability of scoring respiratory disturbance indices and sleep staging.
AB  - STUDY OBJECTIVES: Unattended, home-based polysomnography (PSG) is increasingly
      used in both research and clinical settings as an alternative to traditional
      laboratory-based studies, although the reliability of the scoring of these
      studies has not been described. The purpose of this study is to describe the
      reliability of the PSG scoring in the Sleep Heart Health Study (SHHS), a
      multicenter study of the relation between sleep-disordered breathing measured by
      unattended, in-home PSG using a portable sleep monitor, and cardiovascular
      outcomes. DESIGN: The reliability of SHHS scorers was evaluated based on 20
      randomly selected studies per scorer, assessing both interscorer and intrascorer
      reliability. RESULTS: Both inter- and intrascorer comparisons on epoch-by-epoch
      sleep staging showed excellent reliability (kappa statistics >0.80), with stage 1
      having the greatest discrepancies in scoring and stage 3/4 being the most
      reliably discriminated. The arousal index (number of arousals per hour of sleep)
      was moderately reliable, with an intraclass correlation (ICC) of 0.54. The
      scorers were highly reliable on various respiratory disturbance indices (RDIs),
      which incorporate an associated oxygen desaturation in the definition of
      respiratory events (2% to 5%) with or without the additional use of associated
      EEG arousal in the definition of respiratory events (ICC>0.90). When RDI was
      defined without considering oxygen desaturation or arousals to define respiratory
      events, the RDI was moderately reliable (ICC=0.74). The additional use of
      associated EEG arousals, but not oxygen desaturation, in defining respiratory
      events did little to increase the reliability of the RDI measure (ICC=0.77).
      CONCLUSIONS: The SHHS achieved a high degree of intrascorer and interscorer
      reliability for the scoring of sleep stage and RDI in unattended in-home PSG
      studies.

PMID- 11286352
TI  - Bibliography of recent literature in sleep research.

PMID- 11286353
TI  - Gambling as an addictive disorder among athletes: clinical issues in sports
      medicine.
AB  - This article examines the role of gambling as an addictive disorder experienced
      by athletes, both college and professional. Gambling may often be seen as a
      comorbid factor with other addictions and with depression among athletes. The
      focus on addictions among athletes has gained considerable attention among sports
      medicine clinicians. Diagnostic indicators, risk and protective factors, and a
      stage model of addiction among athletes are addressed. An algorithm and pathway
      of care for athletes with an addictive disorder is offered as are recommendations
      that sports physicians, sports medicine specialists, coaches and counsellors need
      to address athletes who have an addictive disorder.

PMID- 11286354
TI  - Interventions for weight loss and weight gain prevention among youth: current
      issues.
AB  - The recent increase in the prevalence of paediatric obesity is one of the most
      pressing public health concerns today because of the immediate and long term
      health consequences associated with this often intractable disease. Efforts are
      currently being made to reduce the prevalence of paediatric obesity. Youth weight
      loss studies have produced significant long term results. Most of these
      programmes included behaviour modification, diet and exercise. Studies have
      suggested that lifestyle exercise programmes may produce the best long term
      results. Effective components of these programmes appear to be parental
      involvement, reduced intake of foods having high energy density and reductions in
      physical inactivity. Future weight loss studies need to determine the type,
      intensity, and duration of exercise that will produce acceptable adherence and
      consequent long term weight loss, and to ascertain the reinforcing factors that
      determine youth behaviour choice. Weight gain prevention interventions for youth
      are clearly in their infancy. This review describes 3 completed and 2 ongoing
      weight gain prevention trials. One study showed reductions in the prevalence of
      obesity among junior high school girls, but not among boys. Another study among
      elementary school students showed significant mean decreases in body mass index
      in boys and girls following an intervention specifically to reduce time spent
      viewing television. Whether these studies altered food intake or increased
      physical activity remains unclear. A combination of weight loss treatment and
      weight gain prevention strategies employed in parallel is likely to yield the
      greatest benefits. Development and testing of novel intervention strategies,
      using innovative behavioural approaches to increase the likelihood that children
      will adopt healthy dietary, physical activity, and sedentary behaviour patterns,
      holds great promise to significantly reduce the epidemic of obesity.

PMID- 11286358
TI  - Older people and AIDS: quantitative evidence of the impact in Thailand.
AB  - Discussions of the AIDS epidemic rarely consider the impact on older people
      except as infected persons. Virtually no systematic quantitative assessments
      exist of the involvement of parents or other older generation relatives in the
      living and caretaking arrangements of persons with AIDS in either the West or the
      developing world. We assess the extent of such types of involvement in Thailand,
      a country where substantial proportions of elderly parents depend on adult
      children for support and where co-residence with an adult child is common.
      Interviews with local key informants in the public health system in rural and
      urban communities provided quantitative information on a total of 963 adult cases
      who either had died of AIDS or were currently symptomatic. The results indicate
      that a substantial proportion of persons with AIDS move back to their communities
      of origin at some stage of the illness. Two-thirds of the adults who died of an
      AIDS-related disease either lived with or adjacent to a parent by the terminal
      stage of illness and a parent, usually the mother, acted as a main caregiver for
      about half. For 70%, either a parent or other older generation relative provided
      at least some care. The vast majority of the parents were aged 50 or more and
      many were aged 60 or older. This extent of older generation involvement appears
      to be far greater than in Western countries such as the US. We interpret the
      difference as reflecting the contrasting epidemiological and socio-cultural
      situations in Thailand and the West. The fact that older people in Thailand, and
      probably many other developing countries, are extensively impacted by the AIDS
      epidemic through their involvement with their infected adult children has
      important implications for public health programs that address caretaker
      education and social and economic support.

PMID- 11286356
TI  - Factors affecting performance in an ultraendurance triathlon.
AB  - In the recent past, researchers have found many key physiological variables that
      correlate highly with endurance performance. These include maximal oxygen uptake
      (VO2max), anaerobic threshold (AT), economy of motion and the fractional
      utilisation of oxygen uptake (VO2). However, beyond typical endurance events such
      as the marathon, termed 'ultraendurance' (i.e. >4 hours), performance becomes
      harder to predict. The ultraendurance triathlon (UET) is a 3-sport event
      consisting of a 3.8 km swim and a 180 km cycle, followed by a 42.2 km marathon
      run. It has been hypothesised that these triathletes ride at approximately their
      ventilatory threshold (Tvent) during the UET cycling phase. However, laboratory
      assessments of cycling time to exhaustion at a subject's AT peak at 255 minutes.
      This suggests that the AT is too great an intensity to be maintained during a
      UET, and that other factors cause detriments in prolonged performance. Potential
      defeating factors include the provision of fuels and fluids due to finite gastric
      emptying rates causing changes in substrate utilisation, as well as fluid and
      electrolyte imbalances. Thus, an optimum ultraendurance intensity that may be
      relative to the AT intensity is needed to establish ultraendurance intensity
      guidelines. This optimal UET intensity could be referred to as the ultraendurance
      threshold.

PMID- 11286357
TI  - Reliability of power in physical performance tests.
AB  - The reliability of power in tests of physical performance affects the precision
      of assessment of athletes, patients, clients and study participants. In this meta
      analytic review we identify the most reliable measures of power and the factors
      affecting reliability. Our measures of reliability were the typical (standard)
      error of measurement expressed as a coefficient of variation (CV) and the percent
      change in the mean between trials. We meta-analysed these measures for power or
      work from 101 studies of healthy adults. Measures and tests with the smallest CV
      in exercise of a given duration include field tests of sprint running
      (approximately 0.9%), peak power in an incremental test on a treadmill or cycle
      ergometer (approximately 0.9%), equivalent mean power in a constant-power test
      lasting 1 minute to 3 hours on a treadmill or cycle ergometer (0.9 to 2.0%),
      lactate-threshold power (approximately 1.5%), and jump height or distance
      (approximately 2.0%). The CV for mean power on isokinetic ergometers was
      relatively large (> 4%). CV were larger for nonathletes versus athletes (1.3 x),
      female versus male nonathletes (1.4 x), shorter (approximately 1-second) and
      longer (approximately 1-hour) versus 1-minute tests (< or = 1.6 x), and
      respiratory- versus ergometer-based measures of power (1.4 to 1.6 x). There was
      no clear-cut effect of time between trials. The importance of a practice trial
      was evident in studies with > 2 trials: the CV between the first 2 trials was 1.3
      times the CV between subsequent trials; performance also improved by 1.2% between
      the first 2 trials but by only 0.2% between subsequent trials. These findings
      should help exercise practitioners and researchers select or design good measures
      and protocols for tests of physical performance.

PMID- 11286359
TI  - Predictors of decline in self-assessments of health among older people--a 5-year
      longitudinal study.
AB  - Within the framework of the Evergreen project we examined how changes in several
      indicators of health and functioning and physical activity predicted a decline in
      self-assessments of health evaluated over a 5-year period in older people by two
      different measurements: self-rated health (SRH) and self-assessed change in
      health (SACH). The study group comprised all 75-year-old persons born in 1914 (N
      = 382) and living in Jyvaskyla, a town in central Finland. At baseline in 1989,
      91.6%, and at follow-up 5 years later in 1994, 87.3% of those eligible
      participated in the interview and 77.2 and 71.3%, respectively, in the
      examinations in the study centre, focusing on different domains of health and
      functional capacity. One-fifth of the subjects reported a deterioration in and
      one-fifth an improvement in SRH over the 5 years. The rest gave identical self
      assessments of their health at baseline and at follow-up in response to the same
      question. Decline in SRH was associated with a decrease in physical activity and
      cognitive capacity. When asked directly about changes in their health (SACH),
      however, half the subjects said their health had declined. Negative SACH over the
      5-year period was related to an increased number of chronic conditions,
      deterioration in functional performance and physical activity, and to the number
      of chronic conditions at baseline. We suggest that ageing people adapt to changes
      in their objective health and functional performance: the majority tend to assess
      their health as similar to or even better with increasing age despite an increase
      in chronic diseases and decline in functional performance. However, a negative
      SACH indicates that older people are realistic about these negative changes.
      These results support the assumption that the two subjective measurements of
      change in health are based on different criteria: assessment of current general
      health status tends to be based on inter-individual comparison, whereas
      assessment of change in health over a given time period may be based on intra
      individual comparison. Physical activity seems to be an important factor when
      older people assess their health.

PMID- 11286360
TI  - When nurses double as interpreters: a study of Spanish-speaking patients in a US
      primary care setting.
AB  - The United States is experiencing one of its largest migratory waves, so health
      providers are caring for many patients who do not speak English. Bilingual nurses
      who have not been trained as medical interpreters frequently translate for these
      patients. To examine the accuracy of medical interpretations provided by nurses
      untrained in medical interpreting, we conducted a qualitative, cross-sectional
      study at a multi-ethnic, university-affiliated primary care clinic in southern
      California. Medical encounters of 21 Spanish-speaking patients who required a
      nurse-interpreter to communicate with their physicians were videorecorded.
      Encounters were transcribed by blinded research assistants. Transcriptions were
      translated and analyzed for types of interpretive errors and processes that
      promoted the occurrence of errors. In successful interpretations where
      misunderstandings did not develop, nurse-interpreters translated the patient's
      comments as completely as could be remembered and allowed the physician to
      extract the clinically-relevant information. In such cases, the physician
      periodically summarized his/her perception of the problem for back-translation
      and verification or correction by the patient. On the other hand, approximately
      one-half of the encounters had serious miscommunication problems that affected
      either the physician's understanding of the symptoms or the credibility of the
      patient's concerns. Interpretations that contained errors that led to
      misunderstandings occurred in the presence of one or more of the following
      processes: (1) physicians resisted reconceptualizing the problem when
      contradictory information was mentioned; (2) nurses provided information
      congruent with clinical expectations but not congruent with patients' comments;
      (3) nurses slanted the interpretations, reflecting unfavorably on patients and
      undermining patients' credibility; and (4) patients explained the symptoms using
      a cultural metaphor that was not compatible with Western clinical nosology. We
      conclude that errors occur frequently in interpretations provided by untrained
      nurse-interpreters during cross-language encounters, so complaints of many non
      English-speaking patients may be misunderstood by their physicians.

PMID- 11286355
TI  - Chronic fatigue syndrome: an update.
AB  - The chronic fatigue syndrome is characterised by a fatigue that is
      disproportionate to the intensity of effort that is undertaken, has persisted for
      6 months or longer, and has no obvious cause. Unless there has been a long period
      of patient- or physician-imposed inactivity, objective data may show little
      reduction in muscle strength or peak aerobic power, but the affected individual
      avoids heavy activity. The study of aetiology and treatment has been hampered by
      the low disease prevalence (probably <0.1% of the general population), and (until
      recently) by a lack of clear and standardised diagnostic criteria. It is unclear
      how far the aetiology is similar for athletes and nonathletes. It appears that in
      top competitors, overtraining and/or a negative energy balance can be
      precipitating factors. A wide variety of other possible causes and/or
      precipitating factors have been cited in the general population, including
      psychological stress, disorders of personality and affect, dysfunction of the
      hypothalamic-pituitary-adrenal axis, hormonal imbalance, nutritional deficits,
      immune suppression or activation and chronic infection. However, none of these
      factors have been observed consistently. The prognosis is poor; often disability
      and impairment of athletic performance are prolonged. Prevention of overtraining
      by careful monitoring seems the most effective approach in athletes. In those
      where the condition is established, treatment should aim at breaking the vicious
      cycle of effort avoidance, deterioration in physical condition and an increase in
      fatigue through a combination of encouragement and a progressive exercise
      programme.

PMID- 11286361
TI  - Service quality perceptions and patient satisfaction: a study of hospitals in a
      developing country.
AB  - Patients'perceptions about health services seem to have been largely ignored by
      health care providers in developing countries. That such perceptions, especially
      about service quality, might shape confidence and subsequent behaviors with
      regard to choice and usage of the available health care facilities is reflected
      in the fact that many patients avoid the system or avail it only as a measure of
      last resort. Those who can afford it seek help in other countries, while
      preventive care or early detection simply falls by the wayside. Patients'voice
      must begin to play a greater role in the design of health care service delivery
      processes in the developing countries. This study is, therefore, patient-centered
      and identifies the service quality factors that are important to patients; it
      also examines their links to patient satisfaction in the context of Bangladesh. A
      field survey was conducted. Evaluations were obtained from patients on several
      dimensions of perceived service quality including responsiveness, assurance,
      communication, discipline, and baksheesh. Using factor analysis and multiple
      regression, significant associations were found between the five dimensions and
      patient satisfaction. Implications and future research issues are discussed.

PMID- 11286362
TI  - Income and health: the time dimension.
AB  - It is widely recognised that poverty is associated with poor health even in
      advanced industrial societies. But most existing studies of the relationship
      between the availability of financial resources and health status fail to
      distinguish between the transient and permanent impact of poverty on health. Many
      studies also fail to address the possibility of reverse causation; poor health
      causes low income. This paper aims to address these issues by moving beyond the
      static perspective provided by cross-sectional analyses and focusing on the
      dynamic nature of people's experiences of income and health. The specific
      objective is to investigate the relationship between income and health for adult
      participants in the British Household Panel Survey from 1991 to 1996/97. The
      paper pays particular attention to: the problem of health selection; the role of
      long-term income; and, the effect of income dynamics on health. The results
      confirm the general findings from the small number of longitudinal studies
      available in the international literature: long-term income is more important for
      health than current income; income levels are more significant than income
      change; persistent poverty is more harmful for health than occasional episodes;
      and, income reductions appear to have a greater effect on health than income
      increases. After controlling for initial health status the association between
      income and health is attenuated but not eliminated. This suggests that there is a
      causal relationship between low income and poor health.

PMID- 11286363
TI  - The relationship between heart problems and mortality in different social
      classes.
AB  - The aim of this study is to analyze how relative mortality risk varies between
      persons with and without heart problems in different social classes. Cox
      proportional hazards regression was used to analyze relative mortality risk for
      the period 1968-1996 for a Swedish nationally representative sample of 4585
      persons born between 1892 and 1942, and interviewed 1968. Survivors from the
      original sample were also interviewed in 1974, 1981 and 1991 or 1992. "Heart
      problems" is defined as the presence of three mild or one severe symptom
      associated with circulatory problems. Social class is based on occupation. The
      relative mortality risk varied significantly between social classes and between
      persons with and without heart problems, among both men and women. These
      differences were smaller among women than among men. The main results are that
      there are significant additive interactions between social class and heart
      problems among men. Men from lower social classes have a more elevated mortality
      risk than men from higher social classes when they have a heart problem. Among
      white-collar workers the coefficient of the difference between men with and
      without heart problems was 0.53. The corresponding difference was significantly
      larger among workers (1.59, P = 0.01), thus demonstrating an additive
      interaction. The difference was even greater (1.86) among "unclassifiable" men-
      those who could not report an occupation that could be coded into a social class,
      mainly because they were long-term unemployed or on early-retirement pensions.
      Among women, the mortality difference between white-collar workers with and
      without heart problems was 0.85. None of the mortality differences between those
      with and without heart problems in other social classes differed significantly
      from those of white-collar workers. The mortality difference between women with
      and without heart problems was, however, large (2.34) among the "unclassifiable".
      This difference is even larger than the corresponding difference among men.

PMID- 11286364
TI  - Malevolent ogbanje: recurrent reincarnation or sickle cell disease?
AB  - The Igbo of Nigeria believe that everyone is ogbanje (reincarnates) but
      malevolent ogbanje differ from others in being revenge-driven, chronically ill
      and engaging in repeated cycles of birth, death and reincarnation. This study
      examined culturally defined symptoms of 100 children classified as malevolent
      ogbanje; and investigated their family history and child mortality experience.
      There was concordance between cultural descriptions of malevolent ogbanje and
      symptoms as manifested in sickle cell patients. Hemoglobin analysis showed that
      70 of the 100 children had sickle cell disease (SCD); while 68 families had death
      related names. The symptoms associated with Igbo cases of reincarnation, high
      child mortality rates, and the high prevalence of sickle cell disease among
      children classified as malevolent ogbanje all support the conclusion that the
      symptomatology and early mortality experience are related to sickle cell. Names
      with themes of death were prevalent in families of children described as
      malevolent ogbanje. The findings are discussed with reference to cultural
      resistance to SCD as an explanation for malevolent ogbanje and the implications
      for the health care of children with SCD in Nigeria.

PMID- 11286365
TI  - Writing wrongs? An analysis of published discourses about the use of patient
      information leaflets.
AB  - Much has been written about how to communicate with patients, but there has been
      little critical scrutiny of this literature. This paper presents an analysis of
      publications about the use of patient information leaflets. It suggests that two
      discourses can be distinguished in this literature. The first of these is the
      larger of the two. It reflects traditional biomedical concerns and it invokes a
      mechanistic model of communication in which patients are characterised as passive
      and open to manipulation in the interests of a biomedical agenda. The persistence
      of the biomedical model in this discourse is contrasted with the second
      discourse, which is smaller and more recent in origin. This second discourse
      draws on a political agenda of patient empowerment, and reflects this in its
      choice of outcomes of interest, its concern with the use of leaflets as a means
      of democratisation, and its orientation towards patients. It is suggested that
      the two discourses, though distinct, are not entirely discrete, and may begin to
      draw closer as they begin to draw on a wider set of resources, including
      sociological research and theory, to develop a rigorous theoretically grounded
      approach to patient information leaflets.

PMID- 11286366
TI  - A family history of breast cancer: women's experiences from a theoretical
      perspective.
AB  - Individuals at increased risk of developing breast cancer due to their family
      history of the disease face a number of uncertainties. Personal cancer risk
      estimates are imprecise and current methods for early detection or prevention are
      not 100% effective. It is therefore not surprising that adverse psychosocial
      outcomes have been described within this population. Research attempting to
      predict the incidence of distress and dysfunction in individuals at increased
      risk of cancer has been largely a-theoretical and has overlooked a number of
      potentially important predictive variables. In particular, the influence of
      personal experience of cancer through involvement with affected relatives has
      been neglected. There are strong theoretical grounds for hypothesising that
      dimensions of personal experience may influence response to cancer risk. This
      paper discusses the potential impact of personal experience on risk perception,
      illness representations and decision-making. Systematic research in this area may
      improve predictions of outcome of cancer genetic counselling and inform the
      clinical process.

PMID- 11286367
TI  - Return to work after myocardial infarction/coronary artery bypass grafting:
      patients' and physicians' initial viewpoints and outcome 12 months later.
AB  - Nonmedical factors play an important role in determining whether patients resume
      their work after myocardial infarction or CABG. The main questions dealt with in
      this study are: What is the respective basis of physicians' and patients'
      judgements as far as vocational disabilities are concerned, and what are the
      decisive factors that facilitate a prediction as to who will return to work and
      who will not? 132 male patients participating in a cardiac rehabilitation program
      served as subjects. The age group was limited to patients between 40 and 59 yr of
      age. The work situation 12 months following rehabilitation is known for 119
      subjects; 74 had resumed their occupations. Results of regression analyses show
      that patients' and physicians' views on disabilities and re-employment are based
      on different factors. The physicians derive their estimates mainly from medical
      variables (cardiac status and comorbidity), whereas the patients' views are based
      on the overall health status, their former job status, job satisfaction, and
      negative incentives for the return to work. Three variables were found that allow
      a prediction to be made as to re-employment in 85% of all cases: (1) age, (2)
      patients' feelings about the extent to which they are disabled by their cardiac
      problem, and (3) the physicians' views on the extent to which the patient is
      vocationally disabled by his overall medical situation. Medical variables (e.g.
      cardiac status) had little relevance to re-employment. The results are discussed
      with regard to the consequences for cardiac rehabilitation.

PMID- 11286368
TI  - Immigrant women's health.
AB  - The immigration process entails many changes in the lives of those who emigrate
      including establishing oneself in a new country. There is continuing interest in
      what happens to the health of those who undergo this process. This qualitative
      study investigated the perceived health and health-related experiences of a
      sample of mid-life immigrant women and explored relationships between
      determinants of health and their experiences connected to immigration. Forty-two
      women participated in the study. While respondents were relatively well educated,
      their current socioeconomic status was relatively low. While women defined their
      health in a holistic manner. personal health focused on their physical health and
      their ability to function. This functionality was closely related to women's
      roles as resources for their families' well-being. Several health-related themes
      were identified that related to their change in homelands as adults: immigration
      and health, adapting to immigration and rebuilding their lives. Women are
      unlikely to talk about non-physical aspects of health unless asked about the
      general context of their lives. The family-centredness of immigrant women's well
      being is a mediating factor in all aspects of their health; it is the health of
      the family unit that is the final point of adjudication for women. Spirituality
      and religious practices were identified as important resources for health. In
      addition, the process of immigration needs to be recognized as a determinant of
      health in and of itself. An understanding of these conceptualizations and health
      beliefs is an important component of the knowledge to be brought to formulating
      health promotion strategies and health services delivery that are relevant to and
      appropriate for this population of mid-life women.

PMID- 11286369
TI  - Estimating time preferences for health using discrete choice experiments.
AB  - This study is the first to use discrete choice experiments to elicit inter
      temporal preferences for health. Inter-temporal preferences with respect to one's
      own future health are compared with inter-temporal preferences with respect to
      others' future health. Discrete choice experiments are used to measure the
      relative importance of the duration of ill-health and how far in the future the
      ill-health occurs. Data were collected by postal questionnaire in the UK. The
      median implied rates of discount range from 0.055 to 0.091 for own health,
      depending on the period of delay, and from 0.078 to 0.147 for others' health. The
      implied discount rate varies with respect to age, self-rated health, and version
      of the questionnaire. The implied discount rates are broadly comparable with
      other published estimates using closed-ended methods. One concern is the large
      percentage of respondents with dominant preferences. This issue needs to be
      explored before adopting the approach of discrete choice experiments to elicit
      inter-temporal preferences.

PMID- 11286370
TI  - An historical commentary on the physiological effects of music: Tomatis, Mozart
      and neuropsychology.
AB  - This article provides an overview of the theoretical underpinnings of the Tomatis
      Method, along with a commentary on other forms of sound/music training and the
      need for research. A public debate was sparked over the "Mozart Effect." This
      debate has turned out to be unfortunate because the real story is being missed.
      The real story starts with Alfred Tomatis, M.D., scientist and innovator. Dr.
      Tomatis was the first to develop a technique using modified music to stimulate
      the rich interconnections between the ear and the nervous system to integrate
      aspects of human development and behavior. The originating theories behind the
      Tomatis Method are reviewed to describe the ear's clear connection to the brain
      and the nervous system. The "neuropsychology of sound training" describes how and
      what the Tomatis Method effects. Since Dr. Tomatis opened this field in the mid
      20th century, no fewer than a dozen offshoot and related systems of training have
      been developed. Though each new system of treatment makes claims of
      effectiveness, no research exists to substantiate their claims. Rather, each
      simplified system bases its "right to exist and advertise" on the claimed
      relationship to Tomatis and his complex Method. Research is desperately needed in
      this area. The 50 years of clinical experience and anecdotal evidence amassed by
      Tomatis show that sound stimulation can provide a valuable remediation and
      developmental training tool for people of all ages. Offshoot systems have watered
      down the Tomatis Method without research to guide the decisions of simplifying
      the techniques and equipment.

PMID- 11286371
TI  - Effects of Medical Resonance Therapy Music on patients with psoriasis and
      neurodermatitis--a pilot study.
AB  - Stress medicine has shown that emotional disharmony can be a substantial factor
      for skin diseases. The harmonisation of the emotional status and a corresponding
      reduction of stress hormones by the Medical Resonance Therapy Music (MRT-Music)
      as shown in other studies (1,2,3,4) inspired us to investigate its benefits for
      patients with psoriasis vulgaris and neurodermatitis (neurodermatitis
      constitutionalis atopica). Over a period of 14 days we measured the parameters of
      blood pressure, heart rate, stimulus to scratch and the degree of sickness in
      two, respectively four groups of 68 patients in total: two experimental groups
      (psoriasis/neurodermatitis) and two control groups. All patients received the
      normal treatment of our hospital, the experimental groups were additionally
      treated with 3 x 30 minutes of MRT-Music per day, while the controls were asked
      to somehow relax during this time. In the experimental groups the measurements
      showed a reduction of blood pressure and heart rate and revealed an enhanced
      reduction of the stimulus to scratch and an enhanced reduction in the degree of
      sickness. Interestingly the effects of MRT-Music were stronger with the psoriasis
      patients than with the neurodermatitis patients. The results of this pilot study
      convinced us to offer the treatment with the Medical Resonance Therapy Music to
      all our patients.

PMID- 11286372
TI  - Clinical application of Medical Resonance Therapy Music in high-risk pregnancies.
AB  - Music is an ancient method for healing. In the year 550 B.C., Pythagoras from
      Greece developed a concept for the use of music in medicine, esteeming music
      higher than many other medical treatments. The Medical Resonance Therapy Music
      (MRT-Music) of the German classical composer and musicologist Peter Huebner is
      built on this concept of Pythagorean music medicine. Its therapeutic effect may
      be best explained by the natural phenomenon of resonance between the harmony laws
      of the microcosm of music and the biological laws of the body. Results received
      after application of MRT-Music indicate multiple positive effects on the organism
      of pregnant women both with a healthy pregnancy as with a pathologic one,
      reducing the rate of premature births very effectively. Furthermore, MRT-Music
      came out to be an effective method in the complex therapy of late gestoses and a
      nearly irreplaceable method for preoperative preparation of pregnant woman for
      caesarean section. It demonstrated a powerful anti-stress effect and allowed to
      reduce the amount of administered pain-killers to pregnant women by the factor
      1.5 to 2.0, thus reducing the negative pharmacological load to the foetus. It
      furthermore reduced labour time and shortened hospital stay. It helped to create
      optimal conditions for the course of pregnancy and heightened pain sensitivity
      threshold by means of improving the functional, hormonal, and psycho-emotional
      conditions of pregnant and lying-in women. Thus, the labour process became more
      natural, the delivery non-traumatic, and motherhood more happy and safe.

PMID- 11286373
TI  - Effects of the Medical Resonance Therapy Music on haemodynamic parameter in
      children with autonomic nervous system disturbances.
AB  - The present investigation is dedicated to the effects of the Medical Resonance
      Therapy Music (MRT-Music) on basic haemodynamic parameter in children with
      transient arterial hypertension due to disturbances of the autonomic nervous
      system with different degrees of initial sympatheticotonia. After the nuclear
      accident at Chernobyl many children developed blood pressure too high for their
      age norm. Having already observed a decrease in high blood pressure in pregnant
      women during Medical Resonance Therapy Music (Gerasimovich, Einysh,1999;
      Gerasimovich, Sidorenko, 1995; Sidorenko, Tetiorkina, Korotkov, 1997) we studied
      the effects of the Medical Resonance Therapy Music (MRT-Music) on such children
      with very positive results: the treatment with the music preparations
      demonstrated a clear sympatholythic effect and led the disturbed haemodynamic
      state back to its healthy age norm.

PMID- 11286374
TI  - Effects of the Medical Resonance Therapy Music in the complex treatment of
      epileptic patients.
AB  - The purpose of the study was to evaluate the effectiveness of Medical Resonance
      Therapy Music (MRT-Music) as a psycho-physiological method for the treatment of
      epilepsy in severe epileptic patients, whose attacks persevered despite
      comprehensive drug treatments. Under investigation were frequency and severity of
      epileptic attacks, the subjective state, the dynamics of the inter-paroxysmal
      symptoms and the individual parameters of the functional asymmetry of the brain
      (IPFA). Frequency and severity of the paroxysms changed positively in 80 percent
      of the cases: frequency of attacks were reduced by 75 percent and many attacks
      manifested in the form of abortive variants. The paroxysmal component, the degree
      of amnesia and the polymorphism of the attacks were reduced. Such positive
      changes were 4 times less frequent in the control group. Changes in subjective
      state were 90 percent positive: the patients felt more healthy, were calmer, had
      a better mood and fewer ups and downs in mood, released tension, and reduced
      unrest, wrath, and irritation. The evaluation of the Minnesota Multiphasic
      Personality Inventory (MMPI) showed clear improvements in the inter-paroxysmal
      clinical picture, particularly in those parameters that characterise the general
      degree of sickness, psychasthenic and paranoid traits, hypochondria, aggression
      and depressive states. Similar positive changes in the control group were
      observed two times less frequently. The changes of the IPFA-values were positive
      in 73.3 percent of the patients (27.8 percent in controls), had differently
      directed shiftings, were dependent on the initial level, and were determined by
      the location of the epileptic focus.

PMID- 11286375
TI  - Can the Medical Resonance Therapy Music affect autonomous innervation of cerebral
      arteries?
AB  - The purpose of this investigation was to study the effects of Medical Resonance
      Therapy Music (MRT-Music) upon autonomous innervation of cerebral arteries by
      examining slow spontaneous oscillations of cerebral blood flow (SSO) using
      transcranial Doppler ultrasound (TCD). TCD detects SSO with 3-9 cycles per minute
      (M-waves) and 0.5-2 cycles per minute (B-waves). The SSO are caused by rhythmic
      diameter changes of the medium and small cerebral arteries. Six patients aged 24
      65 years suffering from tension headache were treated with MRT-Music. Twelve
      additional patients were examined with TCD only to register SSO for further
      spectral analysis. After fast Fourier transformation four groups of peaks were
      registered on the SSO spectra, divided into four rhythms: A. 0.0-0.02 Hz, B. 0.02
      0.033 Hz, C. 0.06-0.09 Hz, D. 0.09-0.15 Hz and an intermediate diapason of 0.034
      0.059 Hz. Spectral analysis of the SSO showed changes between initial and final
      amplitude peaks in all patients. In contrast to A-, B-and D-rhythms, the
      reduction of peaks in the C-diapason was statistically significant (31-60%, P
      3D0.04, CI 3D95%) for patients treated with MRT-Music. All patients treated with
      the MRT-Music reported a relief of headache while and after treatment.
      CONCLUSION: SSO may represent an equilibrium in autonomous innervation of the
      cerebral arteries. The MRT-Music affects the functioning of the brain structures
      concerning autonomous nervous system and works as a non-chemical sympatholythic.
      Registration of the SSO is a useful tool to prove an influence of the MRT-Music
      upon the autonomous regulation of cerebral vessels.

PMID- 11286376
TI  - Integrative music of the lambdoma.

PMID- 11286377
TI  - Phenylketonuria: tyrosine beyond the phenylalanine-restricted diet.
AB  - Controversies exist on the role of tyrosine in the pathogenesis of
      phenylketonuria (PKU) and, consequently, on the therapeutic role of tyrosine.
      This review examines data and theoretical considerations on the role of tyrosine
      in the pathogenesis and treatment of PKU. It is concluded that treatment with
      tyrosine alone to replace the phenylalanine-restricted diet cannot be justified.
      A treatment with large neutral amino acids (LNAA) including tyrosine to restore
      the balance in the transport of phenylalanine and other LNAA across the blood
      brain barrier deserves further investigation. Such studies should prove the
      safety and the efficacy of such a treatment, finding the optimal dose of all
      LNAA, disclosing the correct age to start and the way to monitor treatment
      biochemically.

PMID- 11286378
TI  - Sequence variations in the NDUFA1 gene encoding a subunit of complex I of the
      respiratory chain.
AB  - NDUFA1 is one of the 36 nuclear genes encoding subunits of the mitochondrial
      complex I involved in the respiratory chain. The human NDUFA1 has been cloned,
      completely sequenced and mapped to Xq24. In the present study, we searched for
      sequence variations in NDUFA1 as causative defects in complex I deficiency using
      genomic DNA of 152 patients with various clinical phenotypes. The patient sample
      consisted of 54 patients (46 male and 8 female) with Leber heriditary optic
      neuropathy (LHON) from 48 unrelated families from Germany and 98 patients (72
      male and 26 female) with biochemically proven complex I deficiency including
      Leigh syndrome. Patient DNA was used to amplify all three exons, including the
      exon/intron boundaries and the promoter region of NDUFA1 for heteroduplex
      analysis and direct sequencing. In the 152 patients tested, no mutation was found
      that could be related to any of the disease phenotypes included. However, three
      single-nucleotide polymorphisms (SNPs) located in the promoter region (SNP G/C at
      nt -71 and SNP T/C at nt -189) and in intron 1 (SNP T/G nt 1454) were discovered.
      Allele frequencies of the SNPs were estimated in a German and Estonian control
      population and compared to complex I-deficient patients. There was no significant
      difference between the control population, the LHON patients, or the severely
      affected patients with complex I deficiency, excluding an association of the
      polymorphisms with the diseases. Our results suggest that mutations in NDUFA1 do
      not cause the gender difference observed in clinically severe and complex
      phenotypes with complex I deficiency.

PMID- 11286380
TI  - Features of carnitine palmitoyltransferase type I deficiency.
AB  - Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty
      acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic'
      and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is
      expressed in liver, kidney and fibroblasts and at low levels in the heart, while
      the other isoform occurs in skeletal muscle and is the predominant form in heart.
      Reported patients with CPT I deficiency lack activity of the hepatic isoform and
      present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with
      raised transaminases, seizures and coma. We discuss four new cases in three
      families showing, variously, renal tubular acidosis, transient hyperlipidaemia
      and, paradoxically, myopathy with elevated creatinine kinase or cardiac
      involvement in the neonatal period as additional features that deserve wider
      recognition.

PMID- 11286379
TI  - Dramatic improvement in mitochondrial cardiomyopathy following treatment with
      idebenone.
AB  - Idebenone, a synthetic analogue of coenzyme Q10, has been shown to improve
      cardiac function in patients with Friedreich ataxia and a deficiency of
      respiratory chain complexes I-III. We describe a woman with severe combined right
      and left heart failure due to a mitochondrial cardiomyopathy. The patient
      underwent an endomyocardial biopsy as part of an evaluation for cardiac
      transplantation. It showed severely decreased respiratory complex activities
      dependent on CoQ, pointing to CoQ depletion. Following idebenone treatment there
      was a dramatic improvement in her clinical status with resolution of the heart
      failure.

PMID- 11286382
TI  - Ornithine carbamoyltransferase deficiency: improved sensitivity of testing for
      protein tolerance in the diagnosis of heterozygotes.
AB  - The most direct test of functional capacity of the liver in nitrogen disposal is
      to stress the urea cycle with a high protein load. This has been used in the
      diagnosis of heterozygosity for ornithine carbamoyltransferase deficiency for
      many years by measuring the subsequent excretion of orotic acid in urine. Reports
      have shown some ambiguity in both this and the more recent allopurinol test. We
      investigated the effects of different foods as the protein load and of different
      analytical methods. A standardized protocol was developed, giving 35 g protein
      per m2 surface area as steamed fat-free chicken breast to be eaten within 30 min.
      Urine was collected at zero time and over 0-2, 2-4 and 4-6 h. Compliance was
      checked by assessing excretion of amino acids. Diagnostic sensitivity was
      improved by reference to the change in excretion, i.e. the ratio of excretions 2
      4 h/0-2 h. Extension of the test to 6 h gave no diagnostic advantage over a 4 h
      test. Comparison of the analysis of total orotic acids by the photometric method
      of Harris and Oberholtzer, the reference method for this study, with that by the
      method of Goldstein and colleagues showed that the latter gave erratic results
      with some false positives. However, comparison of the method of Harris and
      Oberholtzer with specific orotic acid analysis by a modification of the stable
      isotope internal standard method of Rimoldi and colleagues yielded the same
      diagnoses. The improved protein load test gave a clearly positive result in all
      16 obligate heterozygotes and 2 possible heterozygotes tested from 14 kindred,
      and a clearly negative result in all 18 control subjects and all 6 of the
      possible heterozygotes who were later shown by DNA studies not to carry the
      family mutation. The test appears at least as sensitive and specific as the
      allopurinol test, and is more convenient because of the short period of sample
      collection.

PMID- 11286383
TI  - Carnitine palmitoyltransferase I deficiency in neonate identified by dried blood
      spot free carnitine and acylcarnitine profile.
AB  - A neonate at risk for hepatic carnitine palmitoyltransferase I (L-CPT I)
      deficiency was investigated from birth. The free carnitine and acylcarnitine
      profile in dried whole blood filter paper samples collected at ages 1 and 4 days
      showed a markedly elevated concentration of free carnitine (141 and 142
      micromol/L, respectively), normal concentrations of acetyl- and
      propionylcarnitine, with the near absence of all other species. The diagnosis was
      confirmed by in vitro fatty acid oxidation screening assays and enzyme assay in
      cultured skin fibroblasts. Retrospective study of the newborn whole blood sample
      of the index case showed a similar profile (free carnitine 181 micromol/L). The
      newborn population distribution of free carnitine (n = 143,981) showed that only
      three samples had free carnitine > 140 micromol/L (>99.9th centile), two were
      from L-CPT I-deficient neonates and one from a baby with sepsis. While there are
      other conditions that can cause elevated concentrations of free carnitine, an
      isolated elevation of free carnitine only in an apparently healthy term neonate
      warrants further investigation to exclude L-CPT I deficiency.

PMID- 11286381
TI  - Genetic analysis of phytosterolaemia.
AB  - Two women with multiple xanthomas, intermittent arthritis and thrombocytopenia
      were diagnosed as phytosterolaemia, an autosomal-recessive lipid storage disease,
      based on their increased serum concentrations of beta-sitosterol, campesterol and
      sitostanol. The gene responsible for this disease is located within a distance of
      18 cM between microsatellite markers of D2S 1788 and D2S1352 at chromosome 2p21.
      We genotyped the patients and their family members with 16 microsatellite markers
      around this locus. The results from the homozygosity mapping of one family
      suggested that the gene was located within the distance of 12.6 cM between
      D2S2328 and D2S1352. We have shortened the genetic distance by 5.4 cM.

PMID- 11286384
TI  - Survival of two patients with severe delta-aminolaevulinic acid dehydratase
      deficiency porphyria.
AB  - The course of delta-aminolaevulinic acid dehydratase activity was studied over
      the 23 years in erythrocytes of two male patients. The enzyme activity was
      originally 1-2%, which then increased to approximately 8%, of normal levels
      several years after clinical manifestation of the acute hepatic porphyria
      syndrome. Urinary excretions of delta-aminolaevulinic acid and coproporphyrin III
      were excessively increased in the two patients with compound-heterozygous delta
      aminolaevulinic acid dehydratase deficiency porphyria.

PMID- 11286386
TI  - Congenital porto-left renal venous shunt as a cause of galactosaemia.
AB  - Congenital porto left renal venous (PRV) shunt was found to be the cause of
      galactosaemia in four galactosaemic neonates detected by mass screening (Paigen
      method). The patients did not have hereditary galactosaemias and were diagnosed
      as having galactosaemia of unknown cause, because porto-systemic venous (PS)
      shunts had not been recognized. At the time of diagnosis, hypergalactosaemia was
      not severe (0.44-0.55 mmol/L; 8-10 mg/dl) and plasma concentration of total bile
      acids (TBA) did not suggest a PS shunt (46-50 micromol/L). However, slightly but
      consistently increased concentrations of galactose and TBA strongly suggested the
      presence of a PS shunt, and careful ultrasonographic investigation revealed PRV
      shunt. We conclude that PRV shunt should be suspected in patients with
      hypergalactosaemia of unknown cause.

PMID- 11286385
TI  - Peripheral and autonomic nervous system involvement in chronic GM2
      gangliosidosis.
AB  - GM2-gangliosidosis (McKusick 268800 and 272800) is a rare hereditary, progressive
      disorder of ganglioside metabolism caused by deficiency of lysosomal beta
      hexosaminidase (EC 3.2.1.52) activity. It is characterized by severe central
      nervous system involvement. Involvement of the peripheral and autonomic nervous
      system has been suspected but rarely documented in published case reports in the
      chronic form of the disease. Four patients, aged 24-29 years, with chronic GM2
      gangliosidosis were examined prospectively for evidence of peripheral and
      autonomic nervous system dysfunction. All had nerve conduction studies,
      sympathetic skin responses and cardiac monitoring during the head tilt-table
      test. Three patients had objective evidence of autonomic dysfunction with
      abnormal sympathetic nervous skin responses and axonal sensorimotor
      polyneuropathy. None of the patients had evidence of significant cardiovascular
      autonomic dysfunction on the head tilt-table test. The peripheral and autonomic
      nervous system may be involved in patients with chronic GM2-gangliosidosis. In
      some cases, this may be clinically significant. On the other hand, cardiovascular
      autonomic instability is apparently not a significant problem in young adult
      patients with the disease.

PMID- 11286387
TI  - Second spontaneous pregnancy in a galactosaemic woman homozygous for the Q188R
      mutation.

PMID- 11286388
TI  - A new case of succinyl-CoA:acetoacetate transferase deficiency: favourable course
      despite very low residual activity.

PMID- 11286389
TI  - Allelic heterogeneity in Spanish patients with Sanfilippo disease type B.
      Identification of eight new mutations.

PMID- 11286390
TI  - Identification of three novel mutations in the PHKA2 gene in Czech patients with
      X-linked liver glycogenosis.

PMID- 11286391
TI  - Mutation spectrum in patients with fructose-1,6-bisphosphatase deficiency.

PMID- 11286392
TI  - Characterization and application of a gastric surface mucous cell line GSM06
      established from temperature-sensitive simian virus 40 large T-antigen transgenic
      mice.
AB  - It has been indicated that transgenic mouse harboring a temperature-sensitive
      simian virus 40 large T-antigen gene is useful for establishing cell lines from
      tissues that have proved difficult to culture in vitro. The gastric surface
      mucous cell line GSM06 was established from a primary culture of gastric fundic
      mucosal cells of the transgenic mice. GSM06 cells showed temperature-sensitive
      growth in culture and expressed large T-antigen at a permissive temperature (33
      degrees C) but not at a nonpermissive temperature (39 degrees C). At 39 degrees
      C, the cells produced periodic acid-Schiff positive glycoconjugates that formed a
      mucous sheet like the gastric surface mucosa in the stomach. Insulin markedly
      increased the production of glycoconjugates. In addition, proprotein-processing
      endoprotease furin suppression retarded cell growth, but accelerated cell
      differentiation. An air-liquid interface promoted the differentiation of GSM06
      cells in a reconstruction culture with nitrocellulose membrane and collagen gel.
      The gastric surface mucous cell line GSM06 with unique characteristics,
      therefore, should be useful as an in vitro model of the gastric mucosa for
      physiological and pharmacological investigations. Moreover, experiments using
      immortalized cells established in vitro and having specific functions may offer
      an alternative to experiments using living animals and thereby offer a solution
      to this ethical issue.

PMID- 11286393
TI  - Nitrooxy alkyl apovincaminate activates K+ currents in rat neocortical neurons.
AB  - The effects of nitrooxy alkyl apovincaminate VA-045 ((+)-eburunamenine-14
      carboxylic acid(2-nitroxy-ethyl ester), VA) were investigated in acutely
      dissociated rat neocortical neurons by using a nystatin-perforated patch
      recording configuration. VA activated a steady-state outward current in a
      concentration-dependent manner, with an EC50 of 0.65 microM. The reversal
      potential for the current shifted 56.5 mV with tenfold changes in the
      extracellular K+ concentration, suggesting that the current was carried by K+.
      The VA-induced current was not suppressed by apamin (1 microM), charybdotoxin (1
      microM), Cs+ (3 mM), Ba2+ (3 mM), 4-aminopyridine (10 mM) or glibenclamide (10
      microM), whereas tetraethylammonium suppressed the current with an IC50 of 1.4
      mM. These pharmacological properties of the VA-induced current were compatible
      with a slowly inactivating delayed rectifier current (I(K)). It was suggested
      that the current activated by VA was I(K). The VA-induced current was not
      affected by Ca2+ depletion or by staurosporine (0.1 microM), quinacrine (10
      microM), wortmanin (1 microM) or genistein (1 microM). The intracellular
      perfusion of GDPbetaS (0.4 mM) also had no significant effect. Thus, VA may
      directly activate the K+ channels.

PMID- 11286394
TI  - Nitric oxide donating compounds inhibit HCl-induced gastric mucosal lesions
      mainly via prostaglandin.
AB  - Prostaglandin (PG) and nitric oxide (NO) have been known to inhibit the lesion
      formation induced by necrotic agents. However, no clear correlation between PG
      and NO has been shown in the gastroprotective action against necrotic agent
      induced gastric mucosal lesions in rats. Thus, the present study was performed to
      clarify this correlation. Gastric mucosal lesions were induced by the oral
      administration of 0.6 M HCl in rats. 16,16-Dimethyl PGE2 (0.3-3 microg/kg, p.o.;
      dim-PGE2), sodium nitrite (0.3 and 1 mg/kg, s.c.) and sodium nitroprusside (30
      and 100 microg/kg, i.v.; SNP) dose-dependently inhibited the lesion formation.
      Orally administered sodium nitrite or SNP (3 mg/kg) also significantly inhibited
      the lesion formation. The gastroprotective action by dim-PGE2 was not affected by
      the pre-treatment with N(G)-nitro-L-arginine methylester (10 mg/kg, i.v.). The
      gastroprotective effect by sodium nitrite or SNP was markedly attenuated by the
      pre-treatment with indomethacin (10 mg/kg, s.c.). These findings suggest that NO
      donating compounds inhibit the HCl-induced mucosal lesions mainly through
      prostaglandin, but dim-PGE2 directly inhibits the lesions without involvement of
      NO in rats.

PMID- 11286395
TI  - Involvement of prostaglandin E2 in clearance of aggregated protein via protein
      kinase A in glomeruli.
AB  - Recently we immunohistochemically demonstrated that prostaglandin E2 (PGE2)
      promoted the clearance of aggregated bovine serum albumin (a-BSA) deposited in
      glomeruli. Herein, we investigated the role of PGE2 and its signal transduction
      in the disposal of macromolecules in glomeruli. EP2 and EP4 receptor mRNA was
      detected in glomeruli by RT-PCR analysis. A-BSA was injected twice into mice.
      Glomeruli were then isolated and incubated. A-BSA gradually disappeared from
      isolated glomeruli. PGE2 increased the intracellular cyclic AMP and decreased a
      BSA level in glomeruli. Additionally, 8-bromocyclic AMP evoked a loss of a-BSA in
      isolated glomeruli. The effect of 8-bromo-cyclic AMP on the clearance of a-BSA
      was abolished by KT 5720 in glomeruli. PGE2 and 8-bromo-cyclic AMP also prompted
      disposal of a-BSA in cultured mesangial cells. These findings indicate that PGE2
      positively regulates the removal of macromolecules via cyclic AMP and protein
      kinase A in glomeruli, and they provide insight into how to prevent the
      development of glomerulonephritis and glomerulosclerosis.

PMID- 11286396
TI  - Regulation of endothelial nitric oxide synthase and endothelin-1 expression by
      fluvastatin in human vascular endothelial cells.
AB  - We investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme
      A (HMG-CoA) reductase inhibitor, on endothelial vasoactive substances using human
      umbilical vein endothelial cells (HUVECs). Incubation of HUVECs with fluvastatin
      for 12 h increased endothelial nitric oxide synthase (eNOS) mRNA expression in a
      concentration-dependent manner (peak, 276 +/- 38%, mean +/- S.D., of the control,
      at 1.0 microM fluvastatin, P<0.01). In addition, fluvastatin increased eNOS
      protein production (245 +/- 51% of the control level, P<0.05) as well as nitrite
      production (165 +/- 35% of the control level, P<0.01). In contrast, incubation of
      HUVECs with 1.0 microM fluvastatin for 12 h significantly reduced the production
      of endothelin-1 (ET-1) and preproET-1 mRNA expression in HUVECs (28 +/- 1% and 39
      +/- 1% of the control level, respectively, P<0.01). Our results suggest that
      fluvastatin might be involved in improvement of endothelial function and
      prevention of the progression of atherosclerosis.

PMID- 11286397
TI  - Effects of chondroitin sulfate on colitis induced by dextran sulfate sodium in
      rats.
AB  - Chondroitin sulfate (CS) is currently marketed as a therapeutic drug for
      neurodynia, lumbago and arthrodynia. Recently, many clinical studies have
      demonstrated the therapeutic effects of orally administered CS against diseases
      with inflammation. Furthermore, these reports suggest CS plays an important role
      in the protection of the base of ulcers and has anti-inflammatory activity. We
      investigated the effects of CS against dextran sulfate sodium (DSS)-induced rat
      colitis. Rats were given 3% DSS solution for 10 days ad libitum. CS and 5
      aminosalicylic acid (5-ASA) were orally administered daily. The doses of the CS
      groups were 20 or 100 mg/kg and that for the 5-ASA group was 100 mg/kg.
      Evaluations were made of bloody stools, areas of erosion and hematological data.
      CS improved the symptoms of bloody stools, erosion and increase of white blood
      cells. Especially, CS (100 mg/kg) group showed markedly more improvement than the
      5-ASA group. We think that the major mechanism of the therapeutic effects of CS
      are the prevention of tissue damage by the protection of digestive mucosa and
      anti-inflammatory effects. Therefore, CS may have therapeutic value for
      alimentary tract diseases such as inflammatory bowel disease or ulcer.

PMID- 11286398
TI  - Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in
      hyperoxic rat lungs.
AB  - Because it was still uncertain whether a stimulation of beta1-adrenoceptors
      accelerated alveolar fluid clearance in hyperoxic lung injury, the effect of
      denopamine, a selective beta1-adrenergic agonist, on alveolar fluid clearance was
      determined in rats exposed to 93% oxygen for 48 and 56 h. Alveolar fluid
      clearance was measured by the progressive increase in the concentration of Evans
      blue labeled albumin instilled into the alveolar spaces over 1 h at 37 degrees C
      in isolated rat lungs. The principle results were as follows: 1) Although lung
      water volume increased in rats exposed to hyperoxia for 48 and 56 h, basal
      alveolar fluid clearance did not change for up to 56 h; 2) Denopamine increased
      alveolar fluid clearance in rats exposed to hyperoxia as well as in rats without
      exposure to hyperoxia; 3) Denopamine primarily increased amiloride-insensitive
      alveolar fluid clearance in rats exposed to hyperoxia; 4) The potency of
      denopmaine was similar to that of terbutaline, a selective beta2-adrenergic
      agonist. In summary, denopamine is a potent stimulator of alveolar fluid
      clearance in rats exposed to hyperoxia.

PMID- 11286399
TI  - Interactions of ligands at angiotensin II-receptors and imidazoline receptors.
AB  - Ligands for angiotensin II-(AT)-receptors and imidazoline receptors have
      structural similarities and influence blood pressure via various mechanisms. The
      goal of this study was to study the specificity of various ligands by
      displacement experiments. Antazoline, cimetidine, clonidine, efaroxan, guanabenz,
      guanethidine, idazoxan, moxonidine and rilmenidine up to a concentration of 100
      microM failed to displace the specific binding of [125I]Sar1,Ile8 angiotensin II
      at the AT1-receptor characterized by losartan (IC50 = 26 +/- 12 nM) in liver
      homogenate. The same substances up to 100 microM produced no reduction of
      specific [125I]Sar1,Ile8 angiotensin II binding to the AT2-receptor of
      phaeochromocytoma cell membranes characterized by PD123319 (IC50 = 20 +/- 5 nM).
      Displacement experiments at the imidazoline I1-receptors were performed on bovine
      adrenal medulla membranes using [3H]clonidine after characterization by the I1
      ligand clonidine (IC50 = 459 +/- 13 nM) and the I2-ligand idazoxan (IC50 = 3.29
      +/- 0.88 microM). The investigated AT-receptor ligands angiotensin II, losartan,
      EXP 3174 and PD123319 revealed no displacement of [3H]clonidine up to a
      concentration of 100 microM. The I2-receptor in liver homogenate was
      characterized by displacement of [3H]idazoxan by cold idazoxan and clonidine
      (IC50 = 0.37 +/- 0.17 and 68 +/- 31 microM, respectively). The investigated AT
      receptor ligands angiotensin II, losartan and PD123319 failed to displace
      [3H]idazoxan specifically up to 100 microM. Hence, the tested substances showed
      no cross-reactivity at the corresponding AT- and I-receptors up to 100 microM, a
      concentration markedly higher than the plasma concentrations achieved after
      therapeutic application.

PMID- 11286401
TI  - Hemodynamic effects of synephrine treatment in portal hypertensive rats.
AB  - Synephrine, a sympathomimetic alpha1-adrenoceptor agonist, has been shown to
      induce dose-dependent portal hypotensive effects after acute intravenous
      infusion. The present study was undertaken to investigate the hemodynamic effects
      of 8-day administration of synephrine in portal hypertensive rats. Portal
      hypertension was induced by either partial portal vein ligation (PVL) or bile
      duct ligation (BDL). Portal hypertensive rats were allocated into one of two
      groups: vehicle group (0.1 N HCl, 0.5 ml/12 h) or synephrine group (1 mg/kg per
      12 h), with 7 rats in each group. Synephrine or vehicle was administered by
      gavage into PVL and BDL rats for 8 consecutive days. Systemic as well as
      splanchnic hemodynamic parameters were measured thereafter. Synephrine
      significantly ameliorated the hyperdynamic state in both PVL and BDL rats. The
      portal venous pressure in PVL and BDL rats (-13.5% and -10.1%, respectively),
      portal tributary blood flow (-19.5% and -20.4%) and cardiac index (-12.1% and 
      18.8%) were significantly reduced, while mean arterial pressure (10.4% and 23.4%)
      and systemic (26.3% and 51.0%) as well as portal territory (47.1% and 67.7%)
      vascular resistance were enhanced by treatment of synephrine as compared with
      vehicle treatment. Our results showed that eight-day administration of synephrine
      exerted beneficial hemodynamic effects in two models of portal hypertensive rats.

PMID- 11286400
TI  - The anti-inflammatory effect of FR188582, a highly selective inhibitor of
      cyclooxygenase-2, with an ulcerogenic sparing effect in rats.
AB  - The anti-inflammatory and ulcerogenic effects of FR188582, 3-chloro-5-[4
      (methylsulfonyl) phenyl]-1-phenyl-1H-pyrazole, were investigated. In a
      recombinant human cyclooxygenase (COX) enzyme activity, FR188582 inhibited COX-2
      with an IC50 value of 0.017 microM, and the inhibition of prostaglandin (PG) E2
      formation by FR188582 was over 6000 times more selective for COX-2 than COX-1.
      Oral administration of FR188582 dose-dependently inhibited adjuvant arthritis.
      This effect was threefold more potent than that of indomethacin. FR188582 and
      indomethacin dose-dependently suppressed the formation of immunoreactive PGE2,
      but not immunoreactive leukotriene (LT) B4, in arthritic paw. Unlike
      indomethacin, FR188582 did not induce visible gastric lesions in rats at doses up
      to 32 mg/kg, p.o. Furthermore, FR188582 did not inhibit the level of
      immunoreactive PGE2 and immunoreactive 6-keto PGF1alpha in rat gastric mucosa.
      These results suggest that FR188582, a highly selective COX-2 inhibitor, has a
      potent anti-inflammatory effect mediated by inhibition of PGE2 in inflamed
      tissues. The safety profile of FR188582 appears to be improved over the safety
      profile of indomethacin.

PMID- 11286402
TI  - Anxiety-like behavior in elevated plus-maze tests in repeatedly cold-stressed
      mice.
AB  - To clarify the relationship between SART (specific alternation of rhythm in
      temperature) stress (repeated cold stress) and anxiety, the effects of various
      types of stress on the behavior of mice were studied in elevated plus-maze tests
      and then the effects of anxiolytics were evaluated. The percentage of time spent
      in the open arms of the plus-maze apparatus decreased in mice subjected to SART
      stress without change in the total number of arm entries. No change was noted in
      mice subjected to other stresses, such as 1-h, 2-day and 5-day cold stress and 1
      h, 15-h and 5 x 15-h restraint stress. The reduction in the percentage of time
      spent in the open arms caused by SART stress was inhibited by single and repeated
      administrations of diazepam and alprazolam and by a single administration of
      buspirone, which have no influence on the percentage of time spent in the open
      arms in nonstressed mice, but not by flumazenil, WAY-100635 and chronic treatment
      with buspirone. The effects of diazepam and buspirone were antagonized by
      flumazenil and WAY-100635, respectively. The behavior of SART-stressed mice in
      the plus-maze would thus appear to arise from anxiety, to which benzodiazepine
      and serotonin receptors are related, but the diazepam binding inhibitor, an
      endogenous anxiogenic protein, is not. Thus SART-stressed animals may be useful
      for investigating the psychopharmacological and neuropharmacological basis of
      anxiety.

PMID- 11286403
TI  - Disturbance of circadian rhythm in heart rate, blood pressure and locomotive
      activity at the stroke-onset in malignant stroke-prone spontaneously hypertensive
      rats.
AB  - Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP), separated from
      SHRSP, develop severe hypertension and spontaneously develop stroke at early
      ages. Using this model of cerebrovascular stroke, influence of stroke-onset on
      the autonomic nervous system was investigated. Heart rate (HR), systolic and
      diastolic blood pressures (SBP and DBP) and locomotive activity were monitored
      during development of stroke using a telemetry system. Stroke-onset was assessed
      by neurologic symptoms, changes in body weight, fluid intake and serum NOx level.
      The rat displayed a nocturnal pattern of circadian rhythms. At stroke-onset, mean
      HR over 24 h increased by 20 to 30 bpm and rapidly increased at post stroke,
      approximately 100 bpm higher than that at pre stroke. Circadian variation in HR,
      which was normally 50 bpm higher during night than during day, attenuated at
      stroke-onset, and it was blunted or reversed at post stroke. BP variation, which
      was approximately 7 mmHg higher at night than at day, decreased one or two days
      before stroke-onset and reversed at post stroke, especially in DBP. Insufficient
      falls in HR and BP during the day mainly accounted for the disturbed circadian
      variations. Variation of locomotive activity also decreased. These changes serve
      as reliable and accurate markers for stroke-onset in evaluation of drugs for the
      prevention and outcome predictions of stroke.

PMID- 11286404
TI  - Short term hypercholesterolemia alters N(G)-nitro-L-arginine- and indomethacin
      resistant endothelium-dependent relaxation by acetylcholine in rabbit renal
      artery.
AB  - The tension of isolated rings was measured isometrically to compare the N(G)
      nitro-L-arginine- and indomethacin-resistant relaxation by acetylcholine (ACh) in
      the renal artery from normal rabbits and short term hypercholesterolemia rabbits
      (0.5% cholesterol chow for 5 weeks). ACh-induced relaxation in the renal artery
      precontracted with phenylephrine was not influenced by cholesterol-enriched chow.
      However, in comparison with artery from normal rabbits, the N(G)-nitro-L-arginine
      and indomethacin-resistant endothelium-dependent relaxation by ACh was
      significantly enhanced by the chow. The resistant part of ACh-induced relaxation
      was significantly inhibited when the artery was treated with tetraethylammonium
      or SKF 525a. Results suggest that short term hypercholesterolemia modulates
      endothelium-derived hyperpolarizing factor-mediated relaxation in rabbit renal
      artery.

PMID- 11286405
TI  - Formulations and processing of yogurt affect the microbial quality of carbonated
      yogurt.
AB  - Carbonation, flavor, culture type, pH, and storage time were varied to
      investigate the effects of these variables and their interactions on the growth
      of both typical and nontypical yogurt cultures and some contaminating bacteria.
      Two types of yogurt cultures (YC-470 and YC-180) were used as the source of
      typical yogurt bacteria, Streptococcus thermophilus and Lactobacillus delbrueckii
      subsp. bulgaricus. In addition, Lactobacillus acidophilus (LA-K) and
      Bifidobacterium longum ATCC 15707 were added as nontypical yogurt cultures to
      make sweetened low fat (1%) Swiss-style plain, strawberry, and lemon yogurts.
      Samples were incubated at 43 degrees C until pH values of 5.0 or 4.2 were
      reached. Strawberry yogurts at low (4.2) and high (5.0) pHs were divided into
      three portions, which were separately inoculated with contaminating bacteria,
      Bacillus licheniformis ATCC 14580, Escherichia coli ATCC 11775, and Listeria
      monocytogenes Scott A. After incorporation of carbon dioxide (1.10 to 1.27 volume
      of CO2 gas dissolved in water), the yogurt was stored at 4 degrees C for a 90-d
      period. Carbon dioxide did not affect the growth of typical or nontypical yogurt
      bacteria. Also, CO2 did not inhibit the growth of undesirable microorganisms. In
      general, low levels of CO2 did not affect the bacterial population in yogurt. The
      microflora of yogurt were influenced by culture type, pH, flavor type, and
      storage time or their interactions.

PMID- 11286406
TI  - Microbiological and biochemical properties of canestrato pugliese hard cheese
      supplemented with bifidobacteria.
AB  - Canestrato Pugliese cheeses from ewe milk were produced according to a
      traditional protocol and by adding 7.0 log10 cfu of fresh cells per gram of
      Bifidobacterium bifidum Bb02, Bifidobacterium longum Bb46, or both species. The
      traditional technology was modified slightly to favor the survival of probiotic
      microorganisms. After 56 d of ripening, the survival of B. bifidum Bb02 and B.
      longum Bb46 was 6.0 and 5.0 log10 cfu/g, respectively. After 19 d cheeses
      contained ca. 7.0 log10 cfu/g of bifidobacteria. Compared to traditional cheese,
      the addition of bifidobacteria seemed to support the growth and survival of
      mesophilic lactobacilli and Streptococcus thermophilus, used as starter, during
      ripening. No significant differences were observed in the main chemical
      composition, and only a slightly higher concentration of acetic acid was found in
      cheeses with bifidobacteria added. On the contrary, alpha- and beta-galactosidase
      activities were markedly more pronounced in the presence of bifidobacteria,
      especially with B. bifidum Bb02. In contrast with traditional cheese, the lactose
      was completely hydrolyzed in cheeses made with bifidobacteria. Urea-PAGE
      electrophoresis of the pH 4.6-soluble and pH 4.6-insoluble N fractions did not
      show appreciable variations. Only the reversed-phase-HPLC analysis of the pH 4.6
      soluble N showed a slightly more complex profile in the presence of
      bifidobacteria. This finding was in agreement with the higher value of the pH 4.6
      soluble N/total N ratio and with the more pronounced amino-, imino-, and
      dipeptidase activities found in all the cheeses with the bifidobacteria added,
      especially B. bifidum Bb02. No differences were found in the free amino acid and
      free fatty acid contents. The amino acids glutamic acid, valine, proline,
      leucine, and lysine and the fatty acids butyric, caproic, capric, and oleic acids
      were found at the highest concentrations. The sensory evaluation did not show
      significant differences, and Canestrato Pugliese cheeses were characterized by
      small and uniformly distributed eyes, were pale yellow, had an elastic
      consistency and a Pecorino-like smell, were very salty, and tended to be
      moderately piquant.

PMID- 11286407
TI  - Mild isolation procedure discloses new protein structural properties of beta
      lactoglobulin.
AB  - To explore the potentially available functional properties of beta-lactoglobulin
      in, for example, the processing of food products, it is important to isolate the
      protein by a procedure that avoids all possible denaturing conditions, such as
      low pH, high ionic strength, or low or elevated temperatures that could cause the
      protein to undergo irreversible conformational changes. In this work, a mild
      isolation protocol for beta-lactoglobulin from bovine milk is presented,
      applicable to semi large-scale isolations (50 to 200 g). The protein could be
      isolated with a high efficiency (>80%) and a good purity (>98%). Biochemical
      characterization of the material demonstrated no lactosylation of the protein,
      nor the formation of irreversibly associated dimers. Also, no proteose peptones
      could be detected. The ability of beta-lactoglobulin to undergo conformational
      changes is studied by far and near-ultraviolet circular dichroism and
      differential scanning calorimetry. A "global" unfolding of the protein is
      detected around 72 (tertiary level) and 77 degrees C (secondary level). The dimer
      monomer dissociation occurring around 52 degrees C could also be monitored at a
      secondary structural level. Remarkably, a low temperature transition around 30
      degrees C was observed, where approximately 10 beta-stranded residues unfold
      cooperatively, not been reported previously. This low temperature transition is
      irreversible at temperatures higher than 35 degrees C or upon freezing the
      material at -20 degrees C. The addition of 20% glycerol could prevent this
      irreversible conformational change. The effect of the low temperature transition
      on the protein's functionality remains to be investigated.

PMID- 11286408
TI  - The role of coagulase-negative Staphylococcus spp. and associated somatic cell
      counts in the ovine mammary gland.
AB  - The somatic cell count (SCC) of ewes' milk was determined by the Fossomatic
      method and compared with the bacteriological status of the mammary gland. Of 366
      samples from uninfected udder halves, 64.5% had SCC less than 50 x 10(3)
      cells/ml, 81.9% had SCC less than 250 x 10(3), and 92.4% had less than 500 x
      10(3) cells/ml. Of 130 bacteriologically positive samples, 91.1% had SCC more
      than 500 x 10(3) cells/ml and 98.8% more than 250 x 10(3). Of the examined milk
      samples 26.2% showed positive bacteriology during the single sampling. The most
      frequent pathogens isolated from the milk samples were coagulase-negative
      staphylococci. Considering our results, 250 x 10(3) cells/ml should be the
      threshold value, which could be regarded as the upper limit for normal SCC of
      ewes' milk.

PMID- 11286409
TI  - Determination of acetone in cow milk by Fourier transform infrared spectroscopy
      for the detection of subclinical ketosis.
AB  - Fourier transform infrared analysis (FTIR) was used in combination with partial
      least squares regression (PLS) to predict the concentration of acetone in milk.
      FTIR spectra were compared with results of a gas-chromatographic head space
      method. Principal component analysis of whole spectra (3000 to 1000 cm(-1))
      suggested to reduce the spectrum of analysis for acetone to 1450 to 1200 cm(-1).
      A second derivative was applied to the spectra to remove baseline effects and
      further enhance the spectral features. Full cross-validation was used to compare
      the reference with predicted acetone concentrations of samples not included in
      model development. PLS applied to the full spectral range resulted in a complex
      19-factor model with a cross-validation error of 0.22 mM. After reducing the
      spectrum and taking the second derivative, we obtained a model with seven factors
      that yielded a cross-validation error of 0.21 mM. This compares favorably with a
      previously reported model with 20 factors and an error of 0.25 mM. Using PLS
      predictions to identify cows with subclinical ketosis resulted in 95 to 100%
      sensitivity and 96 to 100% specificity when the threshold for subclinical ketosis
      was 0.4 to 1.0 mM. The corresponding positive predictive values were > or = 76%
      and the negative predictive values > 98% throughout an assumed range of
      subclinical ketosis prevalence of 10 to 30%.

PMID- 11286410
TI  - Ketone bodies in milk and blood of dairy cows: relationship between
      concentrations and utilization for detection of subclinical ketosis.
AB  - The objective of this study was to investigate the relationship between the
      concentrations of the different ketone bodies in milk and blood and to evaluate
      these concentrations for the detection of subclinical ketosis. A total of 60
      multiparous cows were used. Concentrations of acetone, acetoacetate, and beta
      hydroxybutyrate were analyzed quantitatively in blood and milk, and the Ketolac
      strip test was used for semiquantitative determination of beta-hydroxybutyrate in
      milk. Cows were defined subclinically ketotic when their concentration of blood
      beta-hydroxybutyrate was over 1200 micromol/L. High correlation coefficients were
      observed between blood acetone and blood acetoacetate, and between blood and milk
      acetone. On the contrary, concentrations of milk and blood beta-hydroxybutyrate
      were poorly correlated with the other concentrations of ketone bodies. The
      Ketolac strip test overestimated the concentrations of beta-hydroxybutyrate in
      milk. For the detection of subclinical ketosis, the best sensitivity-specificity
      combination was obtained with the determination of acetoacetate in blood or milk,
      with threshold concentrations of 125 and 50 micromol/L, respectively.
      Determination of beta-hydroxybutyrate in the milk via an enzymatic analysis or
      via the Ketolac strip test provided valuable results, with threshold
      concentrations of 70 and 100 micromol/L, respectively. The simplicity of use of
      the Ketolac strip test makes it a valuable way to investigate subclinical
      ketosis.

PMID- 11286411
TI  - Analysis of an outbreak of Streptococcus uberis mastitis.
AB  - An outbreak of Streptococcus uberis mastitis was described to gain insight into
      the dynamics of Strep. uberis infections at a herd level. Data were obtained from
      a longitudinal observational study on a commercial Dutch dairy farm with good
      udder health management. Quarter milk samples for bacteriological culture were
      routinely collected at 3-wk intervals from all lactating animals (n = 95 +/- 5).
      Additional samples were collected at calving, clinical mastitis, dry-off, and
      culling. During the 78-wk observation period, 54 Strep. uberis infections were
      observed. The majority of infections occurred during a 21-wk period that
      constituted the disease outbreak. The incidence rate was higher in quarters that
      had recovered from prior Strep. uberis infection than in quarters that had not
      experienced Strep. uberis infection before. The incidence rate of Strep. uberis
      infection did not differ between quarters that were infected with other pathogens
      compared with quarters that were not infected with other pathogens. The expected
      number of new Strep. uberis infections per 3-wk interval was described by means
      of a Poisson logistic regression model. Significant predictor variables in the
      model were the number of existing Strep. uberis infections in the preceding time
      interval (shedders), phase of the study (early phase vs. postoutbreak phase), and
      prior infection status of quarters with respect to Strep. uberis, but not
      infection status with respect to other pathogens. Results suggest that contagious
      transmission may have played a role in this outbreak of Strep. uberis mastitis.

PMID- 11286412
TI  - The effect of extended calving intervals in high-yielding lactating cows on milk
      production and profitability.
AB  - A field trial was conducted to examine the effect of extended calving interval
      (CI) on production and profitability of high yielding cows (n = 937). First
      insemination was performed at 154 and 93 d postpartum (pp), for treatment and
      control primiparous cows, respectively, and at 124 and 71 d pp for treatment and
      control multiparous cows, respectively. During the first experimental lactation,
      average daily value-corrected milk (VCM) yield was 28.5 and 27.7 kg/d of CI for
      treatment (n = 131) and control (n = 133) primiparous cows, respectively. No
      significant difference in average daily VCM yield (33.0 and 32.8 kg/d of CI) was
      found between treatment (n = 271) and control (n = 215) multiparous cows . In the
      first 150 d of the subsequent lactation, there were significant differences in
      milk and VCM production in favor of the treatment primiparous cows (41.4 vs. 39.7
      kg of VCM/d) but no significant differences in the production of multiparous
      cows. Primiparous and multiparous cows with extended lactations were more
      profitable. During the first experimental lactation, there were advantages of
      $0.19 and $0.12/d of CI in the net returns for primiparous cows and multiparous
      cows with longer CI, respectively. When the economic analysis included the first
      experimental lactation plus the first 150 d of the subsequent one, the net return
      per day of CI was higher for cows with an extended voluntary waiting period:
      $0.21/d and $0.16/d for primiparous and multiparous cows, respectively. A delay
      of 60 d with respect to the usual voluntary waiting period in the beginning of
      inseminations of high yielding cows has economic advantages and allows the farmer
      an option for decisions regarding individual cows.

PMID- 11286413
TI  - Effect of oral drenching with zinc oxide or synthetic zeolite A on total blood
      calcium in dairy cows.
AB  - Danish Holstein dairy cows in late lactation and milked in the morning only were
      used as a model for dry pregnant cows to determine the effect of oral drenching
      with zeolite A and zinc oxide, respectively, on total serum calcium. Ten cows
      were assigned randomly to two groups of five cows each, given either synthetic
      zeolite A (group A) or zinc oxide (group B). Blood samples were drawn daily at 10
      a.m. and 10 p.m. during the whole experiment, and total serum calcium was
      determined. Daily fluctuations in blood calcium were recorded, with morning
      values being consistently lower than evening values. Oral drenching with a single
      dose of zinc oxide of 100 mg/kg of body weight as well as with zeolite in doses
      of 500 g of zeolite/cow twice a day for 2.5 d was reflected in serum calcium
      levels. In the group given zeolite A, there was a depression in evening values of
      total serum calcium although the difference did not reach statistical
      significance. It was followed by an increase above baseline level
      ("overshooting"). This was interpreted as a response from the calcium homeostatic
      mechanisms. In the group given a single dose of zinc oxide, a decrease in total
      serum calcium occurred. This decrease was not followed by overshooting,
      indicating that the single treatment with zinc oxide did not stimulate the
      calcium homeostatic mechanisms. The perspective of this first attempt to reduce
      dry cow ration calcium availability may be seen in relation to difficulties in
      formulating dry cows rations from home grown forage sufficiently low in calcium
      to elicit a hypocalcemia protective response at calving.

PMID- 11286414
TI  - Active intestinal absorption of nucleosides by Na+-dependent transport across the
      brush border membrane in cows.
AB  - Transport of 3H-labeled nucleosides across the bovine intestinal brush border
      membrane (BBM) was characterized with BBM vesicles (BBMV) isolated from mid
      jejunum of cows because large amounts of nucleic acids are digested in the small
      intestine of ruminants. Two Na+-dependent electrogenic nucleoside transporters
      with overlapping substrate specificity were shown to be present in the jejunal
      BBM, one for pyrimidine nucleosides and one for purine nucleosides. As indicated
      by inhibitory studies, thymidine seemed to be a specific substrate for the
      pyrimidine nucleoside transporter, while this applied to guanosine and
      deoxyguanosine for the purine nucleoside transporter. Uridine and adenosine
      appear to have an affinity to both transporters. This also applies to
      deoxyadenosine and deoxyuridine. Nucleobases (uracil, hypoxanthine) did not
      affect transport of nucleosides. The kinetic constants (Km and Vmax) for Na
      dependent thymidine and guanosine transport were 29 and 24 micromol/L and 78 and
      51 pmol (mg protein)(-1) s(-1), respectively. These values are much higher than
      those reported for monogastric species.

PMID- 11286416
TI  - The locomotion of dairy cows on floor surfaces with different frictional
      properties.
AB  - The locomotion of dairy cows was evaluated on floors with a smooth epoxy resin
      surface or with a surface-applied bauxite aggregate of mean diameter 0.5, 1.2, or
      2.5 mm (coefficients of static friction, mu 0.35, 0.42, 0.49, and 0.74,
      respectively). Locomotion was recorded as cows walked to receive a food reward.
      Cows on the floor with least friction walked rapidly (0.85 m/s), with frequent,
      short steps. At the start of the supporting phase the upper limbs were more
      vertical. Joint arcs during this phase were reduced. Cows on 0.5-mm aggregate
      also walked rapidly (0.84 m/s); they had the least vertical limb angles and long
      steps but held the hoof more vertical, probably to offset any increased slip
      risk. On floors with larger aggregate, cows decreased speed and step frequency
      but maintained long steps, keeping their upper forelimbs more vertical to reduce
      the supporting limb phase. It is concluded that on a low friction floor (mu <
      0.4), cows walk quickly with frequent, short steps. As mu increases to 0.5, step
      length increases and the number of steps decreases to maintain speed at increased
      friction, producing an optimal coefficient of friction between 0.4 and 0.5.
      Further increases in mu may increase the hanging limb phase at the expense of the
      supporting limb phase, to reduce friction, while maintaining a long stride to
      expedite arrival at the reward.

PMID- 11286415
TI  - Short communication: effects of increased expression of alpha-lactalbumin in
      transgenic mice on milk yield and pup growth.
AB  - Lactose synthase (a complex of beta1,4-galactosyltransferase and alpha
      lactalbumin) forms lactose in the Golgi complex of mammary epithelial cells. To
      determine whether alpha-lactalbumin is a limiting component in this complex,
      transgenic mice that expressed bovine alpha-lactalbumin were studied. Transgenic
      mice produced 0.5 to 1.5 mg/ml of bovine alpha-lactalbumin in their milk, 5- to
      15-fold more alpha-lactalbumin than in milk of control mice. Transgenic and
      control mice produced milk with the same concentrations of lactose, cream, and
      total solids, and showed similar mammary gland growth, morphology, and histology.
      Milk from transgenic mice had 0.6% less protein than milk from control mice (P <
      0.05). The in vitro lactose synthase activity in mammary gland homogenates from
      alpha-lactalbumin transgenic mice was increased (P < 0.05), demonstrating that
      bovine alpha-lactalbumin could interact with murine beta1,4
      galactosyltransferase. Pups reared by lactating transgenic mice showed a 4%
      increase in growth on d 10 of lactation, suggesting that milk production was
      increased (P = 0.06). Milk volume, estimated using the weigh-suckle-weigh
      technique, tended to be higher (although not significantly) in transgenic mice (P
      = 0.11). These results suggest that augmenting alpha-lactalbumin expression in
      the dam increases the growth of suckling offspring.

PMID- 11286417
TI  - Effects of solar radiation and feeding time on behavior, immune response and
      production of lactating ewes under high ambient temperature.
AB  - A 6-wk trial was performed with 40 late-lactation Comisana ewes, which were
      either exposed to or protected from solar radiation and fed either in the morning
      (EXPM, PROM) or afternoon (EXPA, PROA) during summer in a Mediterranean climate.
      Behavioral traits of ewes were recorded once per week from 0800 to 2000 h. Rectal
      temperature (RT) and respiration rate (RR) were measured twice weekly at 1430 h.
      The phytohemagglutinin (PHA) skin test was performed to induce nonspecific
      delayed-type hypersensitivity at d 10, 20, and 32 of the experiment. Jugular
      blood samples were taken from ewes at the beginning and at d 21 and 42 of the
      experiment. Ewe milk yield was recorded daily. Individual milk samples were
      analyzed weekly for milk composition, coagulating properties, somatic cell count
      (SCC) and polymorphonuclear neutrophil leukocyte counts (PMNLC) and every 2 wk
      for bacteriological characteristics. Solar radiation and the interaction of solar
      radiation x time of feeding had significant effects on rectal temperatures. EXPM
      ewes had higher rectal temperatures than EXPA ewes, which in turn exhibited
      higher RT compared with PROM and PROA ewes. EXP groups also had significantly
      higher respiration rates than PRO groups. Immune response was lower in EXPM ewes
      at d 10 and in EXPM, EXPA, and PROM animals at d 20 compared with PROA ewes.
      Exposure to solar radiation resulted in decreased plasma concentrations of
      alanine amino-transferase, alkaline phosphatase, potassium, and magnesium, as
      well as in increased levels of nonesterified fatty acids and aspartate amino
      transferase. Milk yield and composition were not changed by exposure to solar
      radiation and time of feeding, but the EXPM treatment resulted in lower yields of
      casein and fat and reduced clot firmness compared with the three other
      treatments. Milk SCC was similar across treatments, but PMNLC was higher in EXPM
      than in PROM and PROA milk. EXPM animals also had the greatest amounts of total
      and fecal coliforms and of Pseudomonadaceae as well as the highest number of
      mastitis related pathogens in their milk. Results suggest that provision of
      shaded areas can play a major role in helping lactating ewes to minimize the
      adverse effects of high ambient temperatures on thermal balance and energy and
      mineral metabolism. Changing the time of feeding to late afternoon may be
      beneficial to exposed ewes in lowering their heat loads during the warmest hours
      of the day, thereby reducing the detrimental impact of thermal stress on immune
      function and udder health.

PMID- 11286418
TI  - Influence of supplemental, dietary vitamin A on retinol-binding protein
      concentrations in the plasma of preruminant calves.
AB  - Transport of retinol (vitamin A alcohol) from retinoid stores in the liver to
      target tissues is accomplished exclusively by a specific plasma protein, retinol
      binding protein. Within individuals, retinol-binding protein concentrations in
      plasma are regulated and remain constant except in extremes of vitamin A
      nutriture or in disease. In the present study, retinol-binding protein
      concentrations in plasma from preruminant calves supplemented with 0, 1700 (i.e.,
      current NRC requirement), 34,000, or 68,000 IU of vitamin A daily from birth to
      27 d of age (n = 6/treatment) were quantified. Retinol-binding protein
      concentrations at birth averaged 21 microg/ml (n = 24) or approximately 50% of
      concentrations in dairy heifers and cows. Plasma retinol and retinol-binding
      protein concentrations were correlated positively, corroborating the role of
      vitamin A nutriture in the regulation of retinol-binding protein secretion from
      the liver. In this regard, dietary vitamin A influenced positively retinol and
      retinol-binding protein concentrations and, as a consequence, the degree of
      saturation of retinol-binding protein with retinol. At 27 d of age, calves fed >
      or = 34,000 IU of vitamin A had substantially higher retinol and retinol-binding
      protein concentrations than did calves fed < or = 1700 IU of vitamin A,
      indicating that dietary vitamin A effects positively vitamin A status. The data
      also suggest that the current NRC requirement may not be sufficient to assure
      vitamin A adequacy in preruminant calves. Percent saturation of retionol-binding
      protein with retinol in all calves was < 35%, much lower than anticipated and
      suggests that the retinol requirement of vitamin A-responsive tissues exceeded
      vitamin A availability.

PMID- 11286419
TI  - Accuracy and precision of computer models to predict passage of crude protein and
      amino acids to the duodenum of lactating cows.
AB  - To evaluate the ability of several models to accurately and precisely predict the
      passage of crude protein (CP) and amino acids to the duodenum of lactating cows,
      we simulated data from six published studies using the 1989 National Research
      Council equations, the Mepron Dairy Ration Evaluator (version 1.1), the
      University of Pennsylvania release of the Net Carbohydrate and Protein System
      (version 2.12p), the Cornell Net Carbohydrate and Protein System (version 3), and
      CPM Dairy (version 1.0). Models overestimated the passage of CP from microbes by
      an average of 323 g/d, and underestimated the passage of CP from feed by an
      average of 874 g/d. These two errors were partially canceled when CP from
      microbes and feed were summed to estimate passage of total CP to the duodenum.
      Many dietary composition variables appeared to bias the predictions; however, the
      influence of any one variable was small. The efficiency of modeling was high for
      most predictions but was variable for predicting passage of specific individual
      amino acids to the small intestine depending on the model selected. These
      simulations indicated no obvious advantage for any model over the others tested.
      The models responded to changes in diets by altering the amount of protein from
      microbes and feed that reached the duodenum, resulting in improved accuracy of
      predictions of duodenal CP passage compared with simply assuming a constant value
      for passage of CP to the duodenum.

PMID- 11286420
TI  - Prediction of crude protein and amino acid passage to the duodenum of lactating
      cows by models compared with in vivo data.
AB  - To determine whether statistical inferences obtained from predictions by models
      were similar to those of measured data from individual cows, data from six
      research trials published between 1989 and 1997 were simulated using the 1989
      National Research Council Model, the Mepron Dairy Ration Evaluator (version 1.1),
      The University of Pennsylvania release of the Net Carbohydrate and Protein System
      (version 2.12p), The Cornell Net Carbohydrate and Protein System (version 3), and
      the CPM Dairy (version 1.0). Both predicted and measured protein fractions were
      analyzed by ANOVA and compared to determine whether statistical inferences among
      treatments from predictions by the models were similar to those from the measured
      data. The interpretations and statistical inferences of measured data did not
      always agree with those for predicted data. All models responded to changes in
      diet composition and often predicted that dietary changes would result in
      statistically different amounts of protein and amino acids passing to the
      duodenum than were observed in the measured data. The direction of predicted
      change among treatments for passage of nitrogen fractions to the duodenum also
      did not agree with the measured data a large percentage of the time.
      Discrepancies in ANOVA and interpretations between predicted and measured data
      may be due to the reduction in variation associated with modeling biological
      systems, associative effects of feeds not accounted for by models, inadequate
      equations in the models, inadequate description of feeds, or experimental error
      in measured data. Before model simulations of duodenal flow of crude protein and
      amino acids can be substituted for experimental measurements, better descriptors
      of main dietary effects, microbial protein production, ruminal protein
      degradation, and interactions among dietary factors must be developed.

PMID- 11286421
TI  - Effect of dietary lipid source on conjugated linoleic acid concentrations in milk
      fat.
AB  - Conjugated linoleic acids (CLA) found in ruminant milk fat are a byproduct of
      incomplete biohydrogenation of lipids by ruminal bacteria. We examined the effect
      of different dietary fat supplements and processing methods on CLA. In trial 1,
      dietary supplements of Ca salts of fatty acids from canola oil, soybean oil, and
      linseed oil increased CLA content of milk fat by three- to fivefold over the
      control diet. Trials 2 and 3 examined the effect of processing methods for heat
      treatment of full fat soybeans. In trial 2, extrusion, micronizing, and roasting
      resulted in two- to threefold greater concentrations of CLA in milk fat than the
      control diet (raw ground soybeans). In trial 3, different temperatures of
      extrusion (120, 130, and 140 degrees C) increased the CLA content of milk fat to
      a similar extent; CLA averaged 19.9 mg/g of fatty acids for the extrusion
      treatments compared with 4.2 mg/g of fatty acids for the control diet (raw ground
      soybeans). Fish oil (200 and 400 ml/d) was examined in trial 4 and both levels
      resulted in CLA concentrations in milk fat that were about threefold greater than
      the control diet. In trial 5, grain and silage from a high oil corn hybrid
      increased the CLA content of milk fat; however, responses were modest with the
      CLA concentration (mg/g of fatty acids) averaging 4.6 and 2.8 for diets with high
      oil hybrid and normal hybrid, respectively. Similarly, dietary supplements of
      animal fat byproducts (tallow plus yellow grease; trial 6) resulted in modest
      increases in the CLA content of milk fat. Overall, several dietary manipulations
      involving lipid sources and processing methods were identified that allow for a
      marked increase in the conjugated linoleic acid content of milk fat.

PMID- 11286422
TI  - Hot topic: prevention of parturient paresis and subclinical hypocalcemia in dairy
      cows by zeolite A administration in the dry period.
AB  - To test the effects of a zeolite feed supplement on parturient calcium status and
      milk fever, two groups of dry cows were treated with either 1 kg of zeolite/d or
      none for 4 wk prepartum. At calving and d 1 and 2 after calving all cows were
      given 250 g of calcium carbonate as a drench, and a blood sample was taken. Serum
      calcium analysis revealed a greater calcium concentration in zeolite-treated
      cows. While three control cows contracted milk fever, necessitating intravenous
      calcium therapy, and six out of eight control cows experienced serum calcium
      levels below 2 mmol/L in one or more samples taken, none of the zeolite-treated
      cows contracted milk fever or experienced subclinical hypocalcemia.

PMID- 11286423
TI  - Bayesian inference for categorical traits with an application to variance
      component estimation.
AB  - We implemented statistical models of Bayesian inference that included direct and
      maternal genetic effects for genetic parameter estimation of categorical traits
      by Gibbs sampling. The estimation errors and variances of estimates of animal
      versus sire and maternal grandsire models, of linear versus threshold models, of
      single-trait versus multiple-trait models, and of treating herd-year-season as
      fixed versus random effects in the model were compared. The results indicated
      that linear models yielded biased estimates of genetic parameters for categorical
      traits. The animal model was improper for analysis of categorical traits using a
      threshold model and the Gibbs sampler. Moreover, linear versus threshold models
      and animal versus sire-maternal grandsire models resulted in larger Monte Carlo
      errors and increased auto-correlations among posterior samples. Treating herd
      year-seasons as random effects in the threshold models decreased the Monte Carlo
      error, auto-correlations, and the variances of estimates. Efficiency of the
      single-trait threshold sire model, as measured by the variance of the estimates,
      was lower than for a multiple-trait model that included a correlated continuous
      trait, but both estimates were unbiased. Therefore, the threshold single-trait
      sire and maternal grandsire model is a feasible alternative to the multiple-trait
      model for analysis of variance components of categorical traits affected by
      direct and maternal genetic factors.

PMID- 11286424
TI  - Modeling milk production and labor efficiency in modernized Wisconsin dairy
      herds.
AB  - The 1999 Wisconsin Dairy Modernization Project was conducted to examine variation
      in milk production and labor efficiency among herds that had recently expanded.
      Data were obtained from a sample of Wisconsin herds that expanded between 1994
      and 1998. Using rolling herd average milk production in 1998 as the dependent
      variable in the milk production model, milking frequency, bovine somatotropin
      use, sprinkler use, average linear somatic cell score, average age at first
      calving, average days dry, and rolling herd average milk production in 1994
      predicted 69% of the variation in milk production. Milking three times daily,
      using bovine somatotropin, using sprinklers to cool cows, and decreasing linear
      somatic cell score, age at first calving, and days dry were associated with
      increased milk production. Each of these variables supports previous research
      from designed experiments with on-farm results. Variation in milk production is
      determined primarily by differences in management ability and management
      practices employed by the dairy producer. Using cows per full-time equivalent as
      the dependent variable in the labor efficiency model, acres per cow, number of
      people involved in the milking operation, milking system type, herd size, and
      interactions between milking system types and herd size predicted approximately
      43% of the variation in labor efficiency. As expected, labor efficiency increased
      with larger herd sizes, fewer acres per cow, and fewer people involved in the
      milking process. Parallel milking parlors were associated with the highest cows
      per full-time equivalent followed by herringbone parlors, flat barns, and stall
      barns.

PMID- 11286425
TI  - An overview of experiences of Wisconsin dairy farmers who modernized their
      operations.
AB  - Wisconsin dairy producers who modernized their operations between 1994 and 1998
      had positive feelings about their expansion experiences, accompanied by increased
      production and improved profitability and quality of life. The average herd in
      this survey experienced increased production during the 5-yr period studied.
      Nearly all producers were satisfied with their expansion experience. The negative
      effect on milk production normally associated with expansion was minimal for most
      years and did not exist if all herds were summarized together. Managing labor
      appeared to be the most daunting challenge facing producers following expansion.
      Respondents who built all new facilities observed higher production, greater
      labor efficiency, and satisfaction with measures of profitability and quality of
      life than respondents who modified facilities or added no new facilities. As herd
      size increased, milk production, labor efficiency, and satisfaction with herd
      performance, profitability, and quality of life increased. Producers who built
      all new facilities spent less time on farm work, more time managing employees,
      and had less difficulty finding, training, supervising, and keeping farm
      employees than producers who modified facilities or added new facilities to
      existing operations. Larger herds were associated with an increased reliance on
      nonfamily labor. Managing labor appears to be an easier task for managers of
      larger herds. The most difficult challenges for producers who modernized their
      operations were with labor management, financing, and loan procurement,
      construction and cost overruns, and feet and leg health. Difficulties with
      expansion differed little between expansion types (same type, some new, or all
      new facilities) or herd sizes.

PMID- 11286426
TI  - A case-acquisition and decision-support system for the analysis of group-average
      lactation curves.
AB  - A case-acquisition and decision-support system was developed to support the
      analysis of group-average lactation curves and to acquire example cases from
      domain specialists. This software was developed through several iterations of a
      three-step approach involving 1) problem analysis and formulation in consultation
      with two dairy nutrition specialists; 2) development of a case-acquisition and
      decision-support prototype by the system developer; and 3) use of the prototype
      by the domain specialists to analyze and classify milk-recording data from
      example herds. The overall problem was decomposed into three subproblems: removal
      of outlier tests and lactation curves of individual cows; interpretation of group
      average lactation curves; and diagnosis of detected abnormalities at the herd
      level through the identification of potential management deficiencies. For each
      subproblem, a software module was developed allowing the user to analyze both
      graphical and numerical performance representations and classify these
      representations using predefined linguistic descriptors. The example-based method
      for the development of the program proved to be very useful, facilitating the
      communication between system developer and domain specialists, and allowing the
      specialists to explore the appropriateness of the various prototypes developed.
      The resulting software represents a formalization of the approach to group
      average lactation curve analysis, elicited from the two domain specialists. In
      future research, the case-acquisition and decision-support system will be
      complemented with knowledge to automate identified classification tasks, which
      will be captured through the application of machine-learning techniques to
      example cases, acquired from domain specialists using the software.

PMID- 11286427
TI  - The hepatitis C epidemic, shall we remain silent?

PMID- 11286428
TI  - Hepatitis C in methadone maintenance patients: prevalence and public policy
      implications.
AB  - OBJECTIVE: This study measured the extent and examined implications of hepatitis
      C (HCV) infection in a methadone maintenance treatment (MMT) population. METHOD:
      Four hundred and sixty patients were tested for HCV-Ab, hepatic enzymes and
      bilirubin, HCV-RNA, and hepatitis B antibody. RESULTS: Overall, 87% of this
      population had evidence of HCV-Ab. Among drug injectors (IDU), 96% were HCV-Ab
      positive. Among a subset of Laotian opium-smoking patients prevalence was only
      11%. Sixty-two percent of patients with HCV-Ab had detectable HCV-RNA. Only 41%
      had elevated hepatic enzymes, and 5% had elevated bilirubin levels. All age
      groups were equally infected. Systemic problems in screening and treating HCV in
      drug users were identified. CONCLUSION: HCV infection poses significant long-term
      health risks for this population. Harm reduction interventions aimed at reducing
      transmission of HCV and other needle-related infectious disease deserves more
      consideration.

PMID- 11286429
TI  - Hepatitis C: education and counseling issues.
AB  - This paper examines issues and dilemmas faced by counselors and other health care
      providers in addressing the needs of active or recovering alcohol and drug users
      who test positive for HCV. The ambiguities and changing treatment prospects for
      these patients require education and counseling interventions, elements of which
      are described in the paper. Motivational enhancement issues are particularly
      important, to facilitate the patient's commitment to maintain a healthy life
      style while effective treatments are being developed. The high proportion of
      recovering staff in addiction treatment settings adds a level of complexity, as
      their concerns may mirror those of the patients being served, but are rarely
      addressed systematically within the program.

PMID- 11286430
TI  - Crack cocaine--a two-year follow-up of treated patients.
AB  - OBJECTIVES: To investigate the 2-year outcome of the first 131 crack cocaine
      users who had been admitted for a period of inpatient treatment. DESIGN: Follow
      up study of consecutive patients admitted between 1992 and 1994. SETTING:
      Inpatient detoxification unit of a public general hospital in Sao Paulo City,
      Brazil. PARTICIPANTS: 131 consecutive crack cocaine users. MEASURES: Reported
      crack use during last 12 months, incarceration and death. FINDINGS: After 2
      years, 50 patients reported crack use in the last 12 months, 29 said that they
      had not used it during this period, 9 were in prison, 13 had died, 2 had
      disappeared and no information was available on 28. CONCLUSIONS: Crack cocaine
      use seems to be associated with a high mortality rate and criminal involvement
      but about one-third of patients give up using the drug within 2 years of
      inpatient treatment.

PMID- 11286431
TI  - Violent behavior as related to use of marijuana and other drugs.
AB  - The relationship of the degree of use of each of ten types of illicit drugs with
      each of eight types of violent criminal offenses, is reported for an African
      American, inner-city, low SES, young adult study sample (N = 612). Prospective
      data from the time of birth was available for the statistical analyses, to
      provide 51 control variables on factors other than substance use which might
      predict to later violent behavior FINDINGS: Greater frequency of use of marijuana
      was found unexpectedly to be associated with greater likelihood to commit weapons
      offenses; and this association was not found for any of the other drugs, except
      for alcohol. Marijuana use was also found associated with commission of Attempted
      Homicide/Reckless Endangerment offenses. Cocaine/crack and marijuana were the
      only two types of drugs the frequency of use of which was found, for this sample,
      to be significantly related to the frequency of being involved in the selling of
      drugs. These findings may not apply to a middle-class African-American sample.

PMID- 11286432
TI  - Emergence of depression during early abstinence in depressed and non-depressed
      women smokers.
AB  - The emergence of depression early in a quit attempt and its relationship to
      ability to maintain abstinence were studied in 99 depressed and non-depressed
      women smokers. Participants rated withdrawal symptomatology during a baseline
      week and the first two weeks of a quit attempt, during which they used a 21-mg
      nicotine patch and received behavioral counseling. Depressed women experienced
      greater difficulty maintaining early abstinence than non-depressed women. They
      were significantly more likely to smoke on the first day of abstinence and smoked
      marginally more days during the first week. Among participants who relapsed
      during the first two weeks, latency to relapse was significantly shorter for
      depressed women. Although craving and all withdrawal symptoms except insomnia
      showed significant increases over baseline, only depression showed significant
      group differences, with trend analyses suggesting that depression asymptotes in
      non-depressed women after the first week but continues increasing in depressed
      women. Larger increases in depression on the first day of abstinence were
      associated with earlier lapse. Because depression is relatively infrequent as a
      withdrawal symptom, it may not be a "true" withdrawal symptom except in depressed
      people. Identification of depressed smokers and anticipation of their increased
      need for support during this period may help to counteract the "first-day effect"
      and difficulties during early abstinence.

PMID- 11286433
TI  - Adverse outcomes in a controlled trial of pergolide for cocaine dependence.
AB  - We conducted a double-blind, multiple dose comparison study of pergolide versus
      placebo for the treatment of cocaine dependence. In the present study, we
      examined patients who met criteria for cocaine dependence without comorbid
      alcohol dependence (N = 255). Study completion rates favored placebo (48.9%) over
      the low dose (33.3%) and high dose (21.5%) pergolide subjects (chi2(2) = 14.17, p
      < or = 0.001). Treatment effectiveness scores (TES) were significantly higher for
      the placebo group (31.7) than the low dose (25.2) and high dose (14.2) pergolide
      groups (F2,252 = 6.21, p = 0.002). There were no significant differences in side
      effect profiles after first dose of pergolide or placebo, or at study
      termination. Results of this study suggest that pergolide was not efficacious in
      the treatment of cocaine dependence due to reduced study participation. Caution
      regarding the outpatient use of pergolide in similar populations is warranted.

PMID- 11286434
TI  - Hepatitis C, B, D, and A: contrasting features and liver function abnormalities
      in heroin addicts.
AB  - Over 90% of intravenous heroin addicts (IVHAs) carry the hepatitis C virus (HCV).
      The other hepatitis viruses, A, B, D, and G are relatively unimportant in IVHAs
      compared to HCV although active hepatitis B may demonstrate a chronic,
      degenerative course identical to that of HCV. The clinical course of HCV and
      active hepatitis B may span three or more decades. It is helpful to classify
      patients as in the active, cirrhosis, or liver failure stages. Only in the
      active, early stage are the liver enzymes, ALT and AST, likely to be elevated. It
      is this stage that will most likely respond to antiviral therapy. HCV has so many
      extra-hepatic manifestations including immune suppression, collagen diseases, and
      possibly lymphoma and leukemia that the disease is best termed HCV syndrome
      rather than simple hepatitis.

PMID- 11286435
TI  - Methadone treatment: our vision for the future.

PMID- 11286436
TI  - An effect of body massage on voice loudness and phonation frequency in reading.
AB  - The effect of massage on voice fundamental frequency (F(0)) and sound pressure
      level (SPL) was investigated. Subjects were recorded while reading a 3-min
      passage of prose text. Then, a 30-min session of massage was administered by a
      trained naprapathy therapist. Sixteen subjects were given the massage, while 15
      controls rested, lying down in silence for the same amount of time. The subjects
      were then recorded reading the same passage again. The F(0), and SPL averages
      across the whole passage were measured for the pre- and post-treatment
      recordings. In the post-massage recordings, subjects had lowered their F(0) by
      1.1 semitones and their SPL by 1.0 dB, with very high statistical significance.
      The drop in F(0) was somewhat larger for the males than for the females. The
      control subjects showed no effect at all.

PMID- 11286437
TI  - Respiratory function in operatic singing: effects of emotional connection.
AB  - The respiratory patterns of five professional operatic singers when performing
      with "emotional connection" (EC) as if communicating to an audience were compared
      with "technical" (T) singing as if rehearsing. Recordings of the performances
      were played to experienced listeners to provide independent confirmation of the
      singers' intentions. The findings show that, in comparison with T singing, EC
      singing, especially in the aria task, used more air with a greater percentage of
      vital capacity (VC) expired per second, but without a simple association with
      sound pressure level (SPL) or breath (phrase) duration. These findings suggest
      that the performing state of mind itself can effect technical results in operatic
      singing. Pedagogical implications are discussed.

PMID- 11286438
TI  - A real-time interface for a formant speech synthesizer.
AB  - This paper describes a multi-parametric user interface based around the Musical
      Instrument Digital Interface (MIDI) Creator system developed at York which
      provides MIDI data in response to changing pressures on five strain gauge sensors
      to control the fundamental frequency, first three formants and the overall
      amplitude of synthesized speech. Vocal synthesis is achieved by means of a freely
      available time domain formant synthesis system running on a standard PC
      compatible machine. The result is a novel hand-controlled speech synthesizer
      which is not command/phoneme based, but is rather more like a continually
      controlled musical instrument where the speech sounds are shaped in real-time.

PMID- 11286439
TI  - Reliability and content validity of a new instrument for assessment of
      communicative skills and language abilities in young Swedish children.
AB  - The Swedish Early Communicative Development Inventories (SECDI)--w&g (words and
      gestures; 8-16 months) and w&s (words and sentences; 16-28 months)--is a new
      instrument to assess communicative and language abilities in Swedish speaking
      children. Test-retest reliability and content validity of SECDI were examined.
      The results show that the SECDI covers common words in Swedish children's
      vocabulary and that its grammar scale (w&s) incorporates items that develop early
      among many children. Test-retest was analysed over 2 or 3 months, first for 57
      and then for 60 children. Test-retest reliability scores are as follows: SECDI-
      w&g = between 0.70 and 0.90 in most age ranges; and SECDI--w&s = close to or
      above 0.90 on most measures.

PMID- 11286440
TI  - Surgical management of cutaneous squamous cell carcinoma of the head and neck.
AB  - A retrospective audit was made of histological records and hospital case notes of
      patients who had cutaneous squamous cell carcinomas excised from the head and
      neck region at the Maxillofacial Units at St Richard's Hospital, Chichester and
      Southlands Hospital, Shoreham-By-Sea, UK. A total of 227 lesions were excised
      from 183 patients over a 5-year period between 1990 and 1995. The local
      recurrence rate was 4% (9/227) and 12 (7%) of the patients presented with or
      developed regional nodal metastases. Of the 183 patients, 177 (97%) were cured.
      These rates compare favourably with those of other published series of cutaneous
      squamous cell carcinoma managed by surgical techniques that did not follow the
      micrographical technique of Mohs. Certain characteristics may aid in the
      prediction of those cancers that may be more aggressive. It is important to
      evaluate each case in terms of histological grade and site and to design
      management plans to deal with each lesion in the most appropriate way.

PMID- 11286441
TI  - Effect of hyperbaric oxygenation on bone induced by recombinant human bone
      morphogenetic protein-2.
AB  - We examined the effect of hyperbaric oxygen (HBO) therapy on the osteoinductive
      activity of recombinant human bone morphogenetic protein-2 (rhBMP-2), 5mg of
      which was implanted into the calf muscle of rats using atelopeptide type I
      collagen as a carrier. Thirty Wistar rats were divided equally to be given HBO or
      act as controls. New bone formation was measured radiographically, biochemically,
      and histol ogically 3, 7, and 21 days after implantation. In both groups, new
      bone formation was found on day 21. However, there was significantly more new
      bone in the HBO group. In the HBO group, cartilage was present at the outer edge
      of the implanted material on day 7. On days 7 and 21, the local tissue alkaline
      phosphatase activity and calcium content in the HBO group were significantly
      greater than in the control group. These results suggest that HBO accelerated the
      activity and rate of osteoinduction by rhBM P-2.

PMID- 11286442
TI  - Surgical accuracy in Le Fort I maxillary osteotomies.
AB  - The surgical outcome of planned movements of Le Fort I osteotomies is dependent
      on the surgeon's ability to achieve such movements intraoperatively. Our aim was
      to assess the surgical accuracy achieved for 30 consecutive patients undergoing
      Le Fort I osteotomies treated by one maxillofacial surgeon and his team. METHOD:
      Intraoperative control of the mobilized maxilla vertically was achieved by a
      combination of a nasion screw as the external reference point and bony marks
      above and below the osteotomy cuts intraorally. Movements horizontally and
      transversely were controlled with occlusal wafers. The surgical accuracy of
      maxillary movements vertically and horizontally (anteroposteriorly) were assessed
      by standard lateral cephalometric tracings of radiographs taken within two weeks
      prior to operation and 48 hours afterwards. Audit targets were arbitrarily set to
      be satisfactory when the difference between planned movements and actual
      movements as measured on the cephalometric tracings were 2 mm or less. RESULTS:
      The mean (SD) difference from planned vertical movements of the anterior maxilla
      was 0.37 mm (SD 0.64) and horizontal movements 0.85 mm (SD 0.91). Ninety-seven
      percent (29/30) of anterior maxillary movements in the vertical dimension, 90%
      (27/30) of anterior maxillary movements in the horizontal dimension and 87%
      (26/30) of movements in both dimensions had a difference of 2 mm or less. These
      results were comparable with the reported 'gold standard'. CONCLUSION: Good
      surgical accuracy in positioning the mobilized maxilla in Le Fort I osteotomies
      can be achieved with the use of external and internal reference points.

PMID- 11286443
TI  - Cluster headache: review of the literature.
AB  - All papers on cluster headaches were reviewed according to preset criteria under
      the following headings: classification, epidemiology, aetiology, pathophysiology,
      and clinical features. The management review used the Cochrane systematic review
      guidelines and so is based on randomized controlled trials wherever possible. A
      meta-analysis was not done. Other treatments are discussed and their drawbacks
      are highlighted and guidelines proposed based on the evidence of this review.

PMID- 11286444
TI  - Investigation and medical management of trigeminal neuralgia by consultant oral
      and maxillofacial surgeons in the British Isles.
AB  - Trigeminal neuralgia is an extremely painful affliction of the face that is
      treated by various specialists including oral and maxillofacial surgeons. Some
      aspects of its management remain controversial, including screening for secondary
      trigeminal neuralgia, and the monitoring of treatment with carbamazepine. There
      is, however, little information available about current practice. A postal
      questionnaire was sent to 254 fellows of the British Association of Oral and
      Maxillofacial Surgeons (BAOMS) about v arious aspects of the management of
      trigeminal neuralgia. One hundred and seventy nine replies (70%) were received.
      Orofacial and cranial nerve examinations were undertaken by the majority of
      surgeons, but most did not routinely arrange computed tomograp hy or magnetic
      resonance imaging for all patients, nor did they refer the patient to a
      neurologist. In contrast with current recommendations, warnings about the adverse
      effects of carbamazepine were given by only a few surgeons, while most routinely
      monitored full blood counts.

PMID- 11286445
TI  - Postoperative monitoring of flaps by digital camera and Internet link.

PMID- 11286446
TI  - Necrotizing fasciitis of odontogenic origin in Ibadan, Nigeria.
AB  - We reviewed eight patients with necrotizing fasciitis of odontogenic origin.
      There were three women and five men, mean age 58 (range 46-72), and none had any
      associated medical condition such as diabetes. All cases had symptoms of
      toothache for a mean duration of 34 days (range 26-42) before they sought
      treatment. Infection originated in the molar teeth region, and initially
      presented as an odontogenic or periodontal abscess. The clinical features of
      necrotizing fasciitis became apparent only after the superficial fascia had been
      invaded. The transient unusually reddish hue for a dark skin might be explained
      by the fact the deep fascia and muscles were affected before the superficial
      fascia and skin. Necrosis of the skin began in the submandibular region and
      progressed downwards. The necrotic area was less than the extent of infection.
      Antimicrobial treatment, debridement, and fasciotomy improved healing. Delay
      before appropriate treatment had an adverse affect on outcome, and one patient
      died.

PMID- 11286447
TI  - Surgically repaired cleft lips depicted in paintings of the late Gothic period
      and the Renaissance.
AB  - Paintings and drawings by Lucas Moser, Leonardo da Vinci, Albrecht Durer, and
      Jacob Cornelisz van Oostsanen suggest that they employed people who had had cleft
      lips operated on as models for their works of art. Created between 1431 and 1520,
      the portraits show diagnostic facial profiles with a curved nasal dorsum, short
      columella, maxillary retrusion, and pseudoprogenia. The first medical
      illustration of cleft lip surgery was published in 1564 by Ambroise Pare. It was
      therefore late Gothic and Renaissance artists who depicted the conspicuous signs
      of surgically treated patients with cleft lip more than 130 years before the
      surgeons.

PMID- 11286448
TI  - Role of antimicrobials in third molar surgery: prospective, double
      blind,randomized, placebo-controlled clinical study.
AB  - AIM: To test the efficacy of two dosing regimens of antimicrobial prophylaxis
      during the removal of impacted lower third molars. DESIGN: Double blind,
      prospective, placebo-controlled trial. SETTING: Teaching hospital, India.
      SUBJECTS: 151 patients aged 19-36 having impacted lower third molars removed.
      METHODS: Random allocation into three groups: placebo (n= 34), metronidazole 1g
      orally, 1 hour preoperatively (n= 44), or metronidazole 400mg orally eight hourly
      for 5 days postoperatively (n= 47). Patients were recalled on the sixth
      postoperative day for assessment of pain scores on the second and sixth days,
      swelling, differences in mouth opening between preoperative and the sixth
      postoperative day, and the state of the wound. RESULTS: There were no significant
      differences in the outcome between the three groups (P= 0.09). CONCLUSION:
      Antimicrobial prophylaxis does not seem to reduce morbidity after removal of
      lower third molars.

PMID- 11286449
TI  - Hypotensive anaesthesia and blood loss in orthognathic surgery: a clinical study.
AB  - OBJECTIVES: To find out whether hypotensive anaesthesia minimized blood loss
      during orthognathic surgery. DESIGN: A prospective randomized clinical study.
      SUBJECTS AND METHODS: 53 consecutive patients, 15-33 years old, who were to have
      orthognathic operations were admitted to the study. They were randomly allocated
      to either normotensive or hypotensive anaesthesia. RESULTS: Median (range) blood
      loss/operation (ml) under hypotensive anaesthesia was 200 (90-400)ml and under
      normotensive anaesthesia was 350 (130-1575)ml (P= 0.01), and those for maxillary
      segmental osteotomy under hypotensive anaesthesia were 85 (40-240)ml and, under
      normotensive anaesthesia, 175 (100-190)ml (P= 0.05). CONCLUSION: There was
      pronounced reduction in blood loss during orthognathic operations done under
      hypotensive anaesthesia compared with those done under normotensive anaesthesia.

PMID- 11286450
TI  - Acne with chronic recurrent multifocal osteomyelitis involving the mandible as
      part of the SAPHO syndrome: case report.
AB  - For 12 years, a 26-year-old man had acne conglobata and a non-suppurative diffuse
      sclerosing osteomyelitis of the mandible as part of a chronic recurrent
      multifocal osteomyelitis of the sternum, the pelvic bones, and the femoral head,
      and aseptic arthritis of the knee, the fibulotalar, and the sternoclavicular
      joints. This fulfills the formal criteria of the SAPHO syndrome. Repeated
      surgical and antibiotic treatment combined with hyperbaric oxygen caused partial
      improvement. Complete relief and partial disappearance of the scintigraphic
      lesions was achieved with long-term corticosteroids, non-steroidal anti
      inflammatory drugs, minocycline, and isotretinoin.

PMID- 11286451
TI  - Mandibular fractures in Townsville, Australia: incidence, aetiology and treatment
      using the 2.0 AO/ASIF miniplate system.
AB  - In 1995 a total of 114 patients presented with 154 mandibular fractures at the
      Townsville General Hospital, Australia. Fifty-eight (51%) were white, 50 (44%)
      aboriginal, and six (5%) of other or unknown race. One-hundred-and-twenty-four of
      the fractures (81%) occurred in male and 30 (19%) in female patients. Most
      fractures (n= 128, 83%) resulted from fights. The rest being a result of road
      traffic accidents (10%), falls (3%), accidents caused by falling objects (3%) and
      sport accidents (2%). The mandibular angle (n= 66, 43%) and the symphyseal area
      (n= 40, 26%) were the most common fracture sites. Combined fractures were found
      in 30% patients (26%). Of all angle fractures, 97% were related to third molars.
      One-hundred-and-five patients had open reduction by an intraoral approach and
      stabilization by 2.0 AO/ASIF titanium miniplates and nine closed reduction.
      Complications included temporary sensory deficit of the mental nerve (3%), minor
      malocclusion (2%) and infection or dehiscence (5%). We conclude that
      osteosynthesis of mandibular fractures by the 2.0 AO/ASIF titanium miniplate
      system is reliable.

PMID- 11286452
TI  - Extended transbasal approach with preservation of olfaction: ananatomical study.
AB  - Many craniofacial approaches to the sphenoethmoidal region, anterior fossa, and
      central skull base compartment have been described, a number of which involve the
      mobilization of the frontonasoorbital complex en bloc. Spetzler's modification
      incorporates osteotomies around the cribriform plate, to preserve olfaction. In
      this morphological study of three cadavers, photographs were used to show the
      technique and define its anatomical boundaries and limitations. The study
      illustrates access to a number of anatomical regions, particularly the exposure
      of the medial orbit, the cavernous sinus, the clivus, and the vertebrobasilar
      complex.

PMID- 11286453
TI  - Reconstruction of the orbital floor after its removal for malignancy.
AB  - Reconstruction of the orbital floor for malignant disease can be difficult. The
      tissue used should replace the floor itself and the orbital rim to ensure
      appropriate positioning of the globe and to avoid ectropion. The authors present
      a simple technique using temporalis muscle with attached coronoid process of the
      mandible that covers both these areas, and which is suitable for most defects in
      this area.

PMID- 11286454
TI  - A true craniomaxillary fracture.

PMID- 11286455
TI  - Descriptive titles: 'primary' and 'secondary' cleft surgeons.

PMID- 11286456
TI  - Cervicofacial subcutaneous emphysema after oral laser surgery.

PMID- 11286457
TI  - The great auricular and the facial nerve: is there a correlation between the
      diameter of these nerves?

PMID- 11286458
TI  - Re: McCreary CE, McCarten BE. Clinical management of oral lichen planus. Br J
      Oral Maxillofac Surg 1999; 37: 338-343.

PMID- 11286459
TI  - Antibiotics and anticoagulants: beware when prescribing concurrently.

PMID- 11286460
TI  - Quality of life following surgery for oral and pharyngeal malignancy.

PMID- 11286461
TI  - Re: da Silva et al. An unusual foreign body in the tongue. Br J Oral Maxillofac
      Surg 2000; 38: 241-242.

PMID- 11286463
TI  - Adjuvant therapy for gastric cancer - has the standard changed?

PMID- 11286464
TI  - Randomized trial of adjuvant chemotherapy versus control after curative resection
      for gastric cancer: 5-year follow-up.
AB  - Adjuvant chemotherapy of gastric cancer after curative resection is still subject
      to discussion. In this study 137 patients with gastric adenocarcinoma, all with
      positive nodes, were randomized after curative resection so that 69 received
      epidoxorubicin (EPI), leucovorin (LV) and 5-fluorouracil (5-FU) on days 1-3 every
      3 weeks for 7 months, whereas the remaining 68 did not. After a follow-up period
      of 5 years, 21 of the 69 treated patients (30%) and nine controls (13%) were
      still alive; median survival time was 18 months for the controls and 31 months
      for the patients treated with adjuvant chemotherapy (P< 0.01).

PMID- 11286465
TI  - Hormonal therapy with megestrol in inoperable hepatocellular carcinoma
      characterized by variant oestrogen receptors.
AB  - Variant liver oestrogen receptor transcripts in hepatocellular carcinoma are
      associated with aggressive clinical course and unresponsiveness to tamoxifen. To
      evaluate the impact on survival and on tumour growth of megestrol (progestin drug
      acting at post-receptorial level) we enrolled 45 patients with HCC characterized
      by variant liver oestrogen receptors in a prospective, randomized study with
      megestrol vs. placebo. Presence of variant oestrogen receptors was determined by
      RT/PCR. 24 patients were randomized to no treatment and 21 to therapy with
      megestrol 160 mg day(-1). Results were analysed by Kaplan-Meier and Cox methods.
      Survival of hepatocellular carcinoma characterized by variant oestrogen receptors
      was extremely poor (median survival 7 months); megestrol significantly improved
      survival (18 months) (P = 0.0090). Tumour growth at one year was significantly
      slowed down in megestrol-treated patients (P = 0.0212). Bilirubin levels,
      presence of portal thrombosis, HBV aetiology and treatment were identified at
      univariate analysis as factors significantly associated with survival; at
      multivariate analysis, only megestrol therapy (P = 0.0003), presence of HBV
      infection (P = 0.0009) and presence of portal vein thrombosis (P = 0.0051) were
      factors independently related with survival. (1) Megestrol slows down the
      aggressive tumour growth of patients with hepatocellular carcinoma characterized
      by variant estrogen receptors and (2) is also able to favourably influence the
      course of disease, more than doubling median survival.

PMID- 11286467
TI  - Chromosomal radiosensitivity as a marker of predisposition to common cancers?
AB  - We previously found that 40% of breast cancer patients showed enhanced
      sensitivity to X-ray induced chromosome damage in G(2)lymphocytes and suggested
      that this might indicate a low penetrance predisposition to breast cancer, for
      which there is good epidemiological evidence. We have now tested the hypothesis
      that elevated G(2)radiosensitivity is a marker of such predisposition to other
      common cancers. We tested patients with colorectal cancer, for which there is
      also good epidemiological evidence of inherited risk in a substantial proportion
      of cases, and patients with cancers having a strong environmental aetiology (lung
      and cervix). We also repeated our study of breast cancer cases and tested
      patients with chronic diseases other than cancer. The results support our
      hypothesis, in that 30% (12/37) of colorectal cases showed enhanced sensitivity
      compared with 9% (6/66) of normal healthy controls (P = 0.01), whereas the
      proportions of sensitive cervix (11%, 3/27, P = 0.72) and lung cancer cases (23%,
      8/35, P = 0.07) were not significantly above normals. We confirmed the enhanced
      sensitivity of 40% (12/31, P = 0.001) of breast cancer patients and found that
      patients with non-malignant disease had a normal response in the assay (12%,
      4/34, P = 0.73). We suggest that enhanced G(2)chromosomal radiosensitivity is a
      consequence of inherited defects in the ability of cells to process DNA damage
      from endogenous or exogenous sources, of a type that is mimicked by ionizing
      radiation, and that such defects predispose to breast and colorectal cancer.

PMID- 11286466
TI  - Effect of pravastatin on survival in patients with advanced hepatocellular
      carcinoma. A randomized controlled trial.
AB  - Chemotherapy is not effective for hepatocellular carcinoma (HCC). HMG-CoA
      redutase inhibitors have cytostatic activity for cancer cells, but their clinical
      usefulness is unknown. To investigate whether pravastatin, a potent HMG-CoA
      reductase inhibitor, prolongs survival in patients with advanced HCC, this
      randomized controlled trial was conducted between February 1990 and February 1998
      at Osaka University Hospital. 91 consecutive patients <71 years old (mean age 62)
      with unresectable HCC were enroled in this study. 8 patients were withdrawn
      because of progressive liver dysfunction; 83 patients were randomized to standard
      treatment with or without pravastatin. All patients underwent transcatheter
      arterial embolization (TAE) followed by oral 5-FU 200 mg(-1)d for 2 months.
      Patients were then randomly assigned to control (n = 42) and pravastatin (n = 41)
      groups. Pravastatin was administered at a daily dose of 40 mg. The effect of
      pravastatin on tumour growth was assessed by ultrasonography. Primary endpoint
      was death due to progression of HCC. The duration of pravastatin administration
      was 16.5 +/- 9.8 months (mean +/- SD). No patients in either group were lost to
      follow-up. Median survival was 18 months in the pravastatin group versus 9 months
      in controls (P = 0.006). The Cox proportional hazards model showed that
      pravastatin was a significant factor contributing to survival. Pravastatin
      prolonged the survival of patients with advanced HCC, suggesting its value for
      adjuvant treatment.

PMID- 11286468
TI  - Prospective study on gynaecological effects of two antioestrogens tamoxifen and
      toremifene in postmenopausal women.
AB  - To assess and compare the gynaecological consequences of the use of 2
      antioestrogens we examined 167 postmenopausal breast cancer patients before and
      during the use of either tamoxifen (20 mg/day, n = 84) or toremifene (40 mg/day,
      n = 83) as an adjuvant treatment of stage II-III breast cancer. Detailed
      interview concerning menopausal symptoms, pelvic examination including
      transvaginal sonography (TVS) and collection of endometrial sample were performed
      at baseline and at 6, 12, 24 and 36 months of treatment. In a subgroup of 30
      women (15 using tamoxifen and 15 toremifene) pulsatility index (PI) in an uterine
      artery was measured before and at 6 and 12 months of treatment. The mean (+/-SD)
      follow-up time was 2.3 +/- 0.8 years. 35% of the patients complained of vasomotor
      symptoms before the start of the trial. This rate increased to 60.0% during the
      first year of the trial, being similar among patients using tamoxifen (57.1%) and
      toremifene (62.7%). Vaginal dryness, which was present in 6.0% at baseline,
      increased during the use of tamoxifen (26.2%) and toremifene (24.1%). Endometrial
      thickness increased from baseline (3.9 +/- 2.7 mm) to 6.8 +/- 4.2 mm at 6 months
      (P< 0.001), and no difference emerged between the 2 regimens in this regard.
      Before the start of the antioestrogen regimen, the endometrium was atrophic in 71
      (75.5%) and proliferative in 19 of 94 (20.2%) samples; 4 patients had benign
      endometrial polyps. During the use of antioestrogen altogether 339 endometrial
      samples were taken (159 in tamoxifen group, 180 in toremifene group). The
      endometrium was proliferative more often in the tamoxifen group (47.8%) than in
      the toremifene group (32.2%) (P< 0.0001). 20 patients had a total of 24 polyps
      (17 in tamoxifen and 9 in toremifene group, P< 0.05) during the use of
      antioestrogens. One patient in the toremifene group developed endometrial
      adenocarcinoma at 12 months, and one patient had breast cancer metastasis on the
      endometrium. Tamoxifen failed to affect the PI in the uterine artery, but
      toremifene reduced it by 15.0% (P< 0.05) by 12 months. In conclusion, tamoxifen
      and toremifene cause similarly vasomotor and vaginal symptoms. Neither regimen
      led to the development of premalignant endometrial changes. Our data suggest that
      so close endometrial surveillance as used in our study may not be mandatory
      during the first 3 years of use of antioestrogen treatment.

PMID- 11286469
TI  - Brain metastases at the time of presentation of non-small cell lung cancer: a
      multi-centric AERIO analysis of prognostic factors.
AB  - A multi-centre retrospective study involving 4 French university institutions has
      been conducted in order to identify routine pre-therapeutic prognostic factors of
      survival in patients with previously untreated non-small cell lung cancer and
      brain metastases at the time of presentation. A total of 231 patients were
      recorded regarding their clinical, radiological and biological characteristics at
      presentation. The accrual period was January 1991 to December 1998. Prognosis was
      analysed using both univariate and multivariate (Cox model) statistics. The
      median survival of the whole population was 28 weeks. Univariate analysis (log
      rank), showed that patients affected by one of the following characteristics
      proved to have a shorter survival in comparison with the opposite status of each
      variable: male gender, age over 63 years, poor performance status, neurological
      symptoms, serum neuron-specific enolase (NSE) level higher than 12.5 ng ml(-1),
      high serum alkaline phosphatase level, high serum LDH level and serum sodium
      level below 132 mmol l(-1). In the Cox's model, the following variables were
      independent determinants of a poor outcome: male gender: hazard ratio (95%
      confidence interval): 2.29 (1.26-4.16), poor performance status: 1.73 (1.15
      2.62), age: 1.02 (1.003-1.043), a high serum NSE level: 1.72 (1.11-2.68),
      neurological symptoms: 1.63 (1.05-2.54), and a low serum sodium level: 2.99 (1.17
      7.62). Apart from 4 prognostic factors shared in common with other stage IV NSCLC
      patients, whatever the metastatic site (namely sex, age, gender, performance
      status and serum sodium level) this study discloses 2 determinants specifically
      resulting from brain metastasis: i.e. the presence of neurological symptoms and a
      high serum NSE level. The latter factor could be in relationship with the extent
      of normal brain tissue damage caused by the tumour as has been demonstrated after
      strokes. Additionally, the observation of a high NSE level as a prognostic
      determinant in NSCLC might reflect tumour heterogeneity and understimated
      neuroendocrine differentiation.

PMID- 11286470
TI  - Rural and urban differences in stage at diagnosis of colorectal and lung cancers.
AB  - There is evidence that patients living in outlying areas have poorer survival
      from cancer. This study set out to investigate whether they have more advanced
      disease at diagnosis. Case notes of 1323 patients in north and northeast Scotland
      who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed.
      Of patients with lung cancer, 42% (69/164) living 58 km or more from a cancer
      centre had disseminated disease at diagnosis compared to 33% (71/215) living
      within 5 km. For colorectal cancer the respective figures were 24% (38/161) and
      16% (31/193). For both cancers combined, the adjusted odds ratio for disseminated
      disease at diagnosis in furthest group compared to the closest group was 1.59 (P
      = 0.037). Of 198 patients with non-small-cell lung cancer in the closest group,
      56 (28%) had limited disease (stage I or II) at diagnosis compared to 23 of 165
      (14%) of the furthest group (P = 0.002). The respective figures for Dukes A and B
      colorectal cancer were 101 of 196 (52%) and 67 of 172 (39%) (P = 0.025). These
      findings suggest that patients who live remote from cities and the associated
      cancer centres have poorer chances of survival from lung or colorectal cancer
      because of more advanced disease at diagnosis. This needs to be taken into
      account when planning investigation and treatment services.

PMID- 11286471
TI  - Expression of SART3 antigen and induction of CTLs by SART3-derived peptides in
      breast cancer patients.
AB  - We recently reported the SART3 tumour-rejection antigen as possessing tumour
      epitopes capable of inducing HLA-class I-restricted cytotoxic T lymphocytes
      (CTLs). This study investigated expression of the SART3 antigen in breast cancer
      to explore an appropriate molecule for use in specific immunotherapy of breast
      cancer patients. The SART3 antigen was detected in all of the breast cancer cell
      lines tested, 30 of 40 (75%) breast cancer tissue samples, and 0 of 3 non
      tumourous breast tissue samples. SART3 derived peptides at positions 109-118 and
      315-323 induced HLA-A24 restricted CTLs that reacted to breast cancer cells from
      the peripheral blood mononuclear cells (PBMCs) of breast cancer patients.
      Therefore, the SART3 antigen and its peptides could be an appropriate molecule
      for use in specific immunotherapy of the majority of HLA-A24-positive breast
      cancer patients.

PMID- 11286472
TI  - The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in
      cutaneous natural killer/T-cell lymphomas.
AB  - The nasal type, extranodal natural killer or T(NK/T)-cell lymphoma is usually
      associated with latent Epstein-Barr virus (EBV) infection. In order to elucidate
      the EBV gene expression patterns in vivo, we examined eight patients with
      cutaneous EBV-related NK/T-cell lymphomas, including six patients with a NK-cell
      phenotype and two patients with a T-cell phenotype. The implication of EBV in the
      skin lesions was determined by the presence of EBV-DNA, EBV-encoded nuclear RNA
      (EBER) and a clonality of EBV-DNA fragments containing the terminal repeats.
      Transcripts of EBV-encoded genes were screened by reverse transcription-
      polymerase chain reaction (RT-PCR), and confirmed by Southern blot hybridization.
      The expression of EBV-related antigens was examined by immunostaining using
      paraffin-embedded tissue sections and cell pellets of EBV-positive cell lines.
      Our study demonstrated that all samples from the patients contained EBV nuclear
      antigen (EBNA)-1 mRNA which was transcribed using the Q promoter, whereas both
      the Q promoter and another upstream promoter (Cp/Wp) were used in EBV-positive
      cell lines, B95.8, Raji and Jiyoye. Latent membrane protein-1 (LMP-1) mRNA was
      detected in seven of eight patients and all cell lines, whereas EBNA-2
      transcripts were found only in the cell lines. Immunostaining showed no LMP-1,
      EBNA-2 or ZEBRA antigens in the paraffin-embedded tissue sections, although they
      were positive in the cell line cells. Latent BHRF1 transcripts encoding bcl-2
      homologue and BCRF1 transcripts encoding viral interleukin (vIL)-10 were detected
      in one and two of eight patients, respectively. A patient with NK-cell lymphoma
      expressing both transcripts died of rapid progression of the illness. Our results
      indicate that the restricted expression of the latency-associated EBV genes and
      the production of vIL-10 and bcl-2 homologue may favour tumour growth, evading
      the host immune surveillance.

PMID- 11286473
TI  - Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for
      proliferation in serum-free conditions.
AB  - In-vitro and in-vivo studies have shown that autocrine growth factors and
      receptors are frequently expressed in human malignancies. Few of these studies,
      however, provide evidence that the identified autocrine pathway is functional. In
      this study, a functional autocrine growth pathway in pancreatic cancer has been
      identified using an in-vitro cell culture system. When pancreatic cancer cells
      were grown without change of medium, proliferation was greater than when either
      medium was replaced frequently (HPAF, CAPAN-2, PANC-1 or SW1990) or cells were
      grown in the presence of the EGF receptor tyrosine kinase inhibitor AG1478 or the
      MEK inhibitor PD098059 (HPAF or CAPAN-2). Activity of extracellular-regulated
      kinases (ERK) 1 and 2 and c- jun and c- fos mRNA levels were significantly
      elevated in CAPAN-2 cells cultured continuously in serum-free medium.
      Collectively, the observations indicate that the EGF receptor and the ERK MAP
      kinase pathway mediate autocrine signals. In contrast to previous reports, the
      GRP and IGF-I receptors were shown not to be required for autocrine effects on
      pancreatic cancer cell proliferation. Autocrine stimulation of the EGF receptor
      can contribute to sustained mitogenic activity and proliferation of pancreatic
      cancer cells.

PMID- 11286474
TI  - Differential regulation of cell proliferation and protease secretion by epidermal
      growth factor and amphiregulin in tumoral versus normal breast epithelial cells.
AB  - Amphiregulin (AR) is a heparin-binding epidermal growth factor (EGF)-related
      peptide that seems to play an important role in mammary epithelial cell growth
      regulation. We have investigated the regulation of AR-gene expression and 
      protein secretion by EGF in normal breast epithelial cells (HMECs), as well as in
      the tumoral breast epithelial cell lines MCF-7 and MDA-MB231. EGF induced a dose
      dependent increase of AR mRNA level in both normal and tumoral cells. Thus, 10(
      8)M EGF stimulated AR expression in HMECs to 140-300% of control. A similar EGF
      concentration increased AR mRNA level to 550% and 980% of control in MCF-7 and
      MDA-MB231 cells, respectively. This was accompanied by an accumulation of AR into
      conditioned culture media. However, HMECs secreted in response to EGF, 5-10 fold
      more AR than tumour cells. Furthermore, the potential participation of AR in the
      regulation of the plasminogen activator (PA)/plasmin system was investigated.
      Whereas HMEC-proliferation was stimulated by AR, the levels of secreted urokinase
      type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAi
      1) remained unaffected. Conversely, AR failed to regulate the proliferation of
      tumoral cell lines but induced an accumulation of uPA and PAi-1 into culture
      media. This was accompanied by an increase of the number of tumoral cells that
      invaded matrigel in vitro. Moreover, the presence of a neutralizing anti-uPA
      receptor antibody reversed the increased invasiveness of MDA-MB231 cells induced
      by AR. These data reveal differential behaviour of normal versus tumoral breast
      epithelial cells in regard to the action of AR and demonstrate that, in a number
      of cases, AR might play a significant role in tumour progression through the
      regulation of the PA/plasmin system.

PMID- 11286475
TI  - Activation of Ca(2+)-dependent proteolysis in skeletal muscle and heart in cancer
      cachexia.
AB  - Cachexia is a syndrome characterized by profound tissue wasting that frequently
      complicates malignancies. In a cancer cachexia model we have shown that protein
      depletion in the skeletal muscle, which is a prominent feature of the syndrome,
      is mostly due to enhanced proteolysis. There is consensus on the views that the
      ubiquitin/proteasome pathway plays an important role in such metabolic response
      and that cytotoxic cytokines such as TNFalpha are involved in its triggering
      (Costelli and Baccino, 2000), yet the mechanisms by which the relevant
      extracellular signals are transduced into protein hypercatabolism are largely
      unknown. Moreover, little information is presently available as to the possible
      involvement in muscle protein waste of the Ca(2+)-dependent proteolysis, which
      may provide a rapidly activated system in response to the extracellular signals.
      In the present work we have evaluated the status of the Ca(2+)-dependent
      proteolytic system in the gastrocnemius muscle of AH-130 tumour-bearing rats by
      assaying the activity of calpain as well as the levels of calpastatin, the
      natural calpain inhibitor, and of the 130 kDa Ca(2+)-ATPase, both of which are
      known calpain substrates. After tumour transplantation, total calpastatin
      activity progressively declined, while total calpain activity remained unchanged,
      resulting in a progressively increasing unbalance in the calpain/calpastatin
      ratio. A decrease was also observed for the 130 kDa plasma membrane form of
      Ca(2+)-ATPase, while there was no change in the level of the 90 kDa sarcoplasmic
      Ca(2+)-ATPase, which is resistant to the action of calpain. Decreased levels of
      both calpastatin and 130 kDa Ca(2+)-ATPase have been also detected in the heart
      of the tumour-bearers. These observations strongly suggest that Ca(2+)-dependent
      proteolysis was activated in the skeletal muscle and heart of tumour-bearing
      animals and raise the possibility that such activation may play a role in
      sparking off the muscle protein hypercatabolic response that characterizes cancer
      cachexia.

PMID- 11286477
TI  - Dexrazoxane significantly impairs the induction of doxorubicin resistance in the
      human leukaemia line, K562.
AB  - Dexrazoxane combined with doxorubicin (+ 5-fluorouracil + cyclophosphamide - the
      FAC regime) leads to a significant decrease in doxorubicin cardiotoxicity and a
      significant increase in median survival time for patients with advanced breast
      cancer responsive to FAC. The reason for this increase in survival may be due to
      interference with the mechanism involved in the emergence of multidrug resistance
      (MDR). In order to test this hypothesis, we induced resistance to doxorubicin in
      the K562 cell line by growing cells in increasing concentrations of doxorubicin
      (10-30 nM) in the presence and absence of dexrazoxane (20 nM). The doxorubicin
      sensitivity of all resultant sublines was measured using the MTT assay. Flow
      cytometry was used to assess the MDR1 phenotype, measuring P-glycoprotein
      expression with MRK 16 antibody and drug accumulation in the presence and absence
      of PSC 833 for functional P-glycoprotein. Long-term growth in doxorubicin
      increased the cellular resistance (IC(50)) of K562 cells in a concentration
      dependent manner (r(2 )= 0.908). Doxorubicin resistance was not induced in the
      presence of dexrazoxane (P< 0.0001) for several months. In parallel, the
      expression of functional P-glycoprotein was delayed after concomitant addition of
      dexrazoxane to the selecting medium (P< 0.001). Dexrazoxane did not act as a
      conventional modulator of P-glycoprotein. These results suggest that dexrazoxane
      may delay the development of MDR1, thus allowing responders to the FAC regime to
      continue to respond.

PMID- 11286476
TI  - Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal
      rat osteosarcoma cell line.
AB  - Local growth of osteosarcoma involves destruction of host bone by proteolytic
      mechanisms and/or host osteoclast activation. Osteoclast formation and activity
      are regulated by osteoblast-derived factors such as the osteoclast
      differentiating factor, receptor activator of NF-kappaB ligand (RANKL) and the
      inhibitor osteoprotegerin (OPG). We have investigated the in vitro effects of
      bisphosphonates on a clonal rat osteosarcoma cell line. The aminobisphosphonate
      pamidronate was added to UMR 106-01 cell cultures (10(-8)M to 10(-4)M up to 5
      days). The non-aminobisphosphonate clodronate was administered for the same time
      periods (10(-6)M to 10(-2)M). Cell proliferation, apoptosis and mRNA expression
      was assessed. Both agents inhibited cell proliferation in a time- and dose
      dependent manner. ELISA analysis demonstrated an increase in DNA fragmentation
      although there was no significant dose-related difference between the doses
      studied. Bisphosphonate-treated cultures had a greater subpopulation of cells
      exhibiting morphological changes of apoptosis. Expression of mRNA for osteopontin
      and RANKL was down-regulated by both agents, while the expression of mRNA for
      alkaline phosphatase, pro-alpha1(I) collagen and OPG was not altered. Out in
      vitro work suggests the bisphosphonates not only have direct effects on
      osteosarcoma cell growth and apoptosis, but also, by altering the relative
      expression of osteoclast-regulating factors, they may inhibit the activity of
      osteoclasts and their recruitment.

PMID- 11286478
TI  - Aspirin and risk for gastric cancer: a population-based case-control study in
      Sweden.
AB  - While aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) are
      associated with gastric mucosal damage, they might reduce the risk for gastric
      cancer. In a population-based case-control study in 5 Swedish counties, we
      interviewed 567 incident cases of gastric cancer and 1165 controls about their
      use of pain relievers. The cases were uniformly classified to subsite (cardia/non
      cardia) and histological type and information collected on other known risk
      factors for gastric cancer. Helicobacter pylori serology was tested in a subset
      of 542 individuals. Users of aspirin had a moderately reduced risk of gastric
      cancer compared to never users; odds ratio (OR) adjusted for age, gender and
      socioeconomic status was 0.7 (95% CI = 0.6-1.0). Gastric cancer risk fell with
      increasing frequency of aspirin use (P for trend = 0.02). The risk reduction was
      apparent for both cardia and non-cardia tumours but was uncertain for the diffuse
      histologic type. No clear association was observed between gastric cancer risk
      and non-aspirin NSAIDs or other studied pain relievers. Our finding lends support
      to the hypothesis that use of aspirin reduces the risk for gastric cancer.

PMID- 11286479
TI  - Familial colorectal adenocarcinoma and hereditary nonpolyposis colorectal cancer:
      a nationwide epidemiological study from Sweden.
AB  - Although estimates are available of the proportion of hereditary nonpolyposis
      colorectal cancer (HNPCC) among all colorectal cancer (CRC), its proportion among
      familial CRC is unclear. We estimated these proportions epidemiologically from
      the nationwide Swedish Family-Cancer Database on 9.6 million individuals.
      Colorectal adenocarcinomas were retrieved from the Cancer Registry covering years
      1958-1996. Standardized incidence ratios (SIRs) were calculated for offspring
      (aged less than 62 years) when their parent had colorectal adenocarcinoma. In
      9.82% of all families, an offspring and a parent were affected, giving a
      population attributable proportion of 4.91% and a familial SIR of 2.00. When
      offspring and parents shared the anatomic site, the SIR was 2.32 for proximal and
      2.00 for distal CRC. When offspring were diagnosed before age 40 years and
      parents before age 50 years, the SIR was 25.72 for familial proximal CRC. In
      older age groups familial risks did not differ between proximal and distal CRC.
      Familial risks were increased also for endometrial, small intestinal and gastric
      cancers, manifestations in HNPCC. Depending on which assumptions were made, HNPCC
      was calculated to account for 20 to 50% of familial CRC, corresponding to 1 or
      2.5% of all CRC among 0-61-year-old individuals.

PMID- 11286482
TI  - Parental cancer as a risk factor for nine common childhood malignancies.
AB  - The nationwide Swedish Family-Cancer Database was used to analyse childhood
      tumours among 8158 offspring by parental cancers. The results showed 2-fold
      familial increases for nervous system cancers and lymphomas, a 6.4-fold increase
      for endocrine tumours, a 60-fold increased risk for retinoblastomas but no excess
      risk for leukaemia and Wilms tumour.

PMID- 11286481
TI  - Frequent k- ras -2 mutations and p16(INK4A)methylation in hepatocellular
      carcinomas in workers exposed to vinyl chloride.
AB  - Vinyl chloride (VC) is a know animal and human carcinogen associated with liver
      angiosarcomas (LAS) and hepatocellular carcinomas (HCC). In VC-associated LAS
      mutations of the K- ras -2 gene have been reported; however, no data about the
      prevalence of such mutations in VC associated HCCs are available. Recent data
      indicate K- ras -2 mutations induce P16 methylation accompanied by inactivation
      of the p16 gene. The presence of K- ras -2 mutations was analysed in tissue from
      18 patients with VC associated HCCs. As a control group, 20 patients with
      hepatocellular carcinoma due to hepatitis B (n = 7), hepatitis C (n = 5) and
      alcoholic liver cirrhosis (n = 8) was used. The specific mutations were
      determined by direct sequencing of codon 12 and 13 of the K- ras -2 gene in
      carcinomatous and adjacent non-neoplastic liver tissue after microdissection. The
      status of p16 was evaluated by methylation-specific PCR (MSP), microsatellite
      analysis, DNA sequencing and immunohistochemical staining. All patients had a
      documented chronic quantitated exposure to VC (average 8883 ppmy, average
      duration: 245 months). K- ras -2 mutations were found in 6 of 18 (33%) examined
      VC-associated HCCs and in 3 cases of adjacent non-neoplastic liver tissue. There
      were 3 G --> A point mutations in the tumour tissue. All 3 mutations found in non
      neoplastic liver from VC-exposed patients were also G --> A point mutations
      (codon 12- and codon 13-aspartate mutations). Hypermethylation of the 5' CpG
      island of the p16 gene was found in 13 of 18 examined carcinomas (72%). Of 6
      cancers with K- ras -2 mutations, 5 specimens also showed methylated p16. Within
      the control group, K- ras -2 mutation were found in 3 of 20 (15%) examined HCC.
      p16 methylation occurred in 11 out of 20 (55%) patients. K- ras -2 mutations and
      p16 methylation are frequent events in VC associated HCCs. We observed a K- ras 
      2 mutation pattern characteristic of chloroethylene oxide, a carcinogenic
      metabolite of VC. Our results strongly suggest that K- ras -2 mutations play an
      important role in the pathogenesis of VC-associated HCC.

PMID- 11286480
TI  - Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a
      prospective study.
AB  - We assessed the association of postmenopausal serum levels of oestrogens and sex
      hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control
      study nested within the NYU Women's Health Study cohort. Among 7054 women
      postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a
      median of 5.5 years after blood donation. Each case was compared to 4 controls
      matched on age, menopausal status at enrolment, and serum storage duration.
      Endometrial cancer risk increased with higher levels of oestradiol (odds ratio =
      2.4 in highest vs lowest tertile, P for trend = 0.02), percent free oestradiol
      (OR = 3.5, P< 0.001), and oestrone (OR = 3.9, P< 0.001). Risk decreased with
      higher levels of percent SHBG-bound oestradiol (OR = 0.43, P = 0.03) and SHBG (OR
      = 0.39, P = 0.01). Trends remained in the same directions after adjusting for
      height and body mass index. A positive association of body mass index with risk
      was substantially reduced after adjusting for oestrone level. Our results
      indicate that risk of endometrial cancer increases with increasing postmenopausal
      oestrogen levels but do not provide strong support for a role of body mass index
      independent of its effect on oestrogen levels.

PMID- 11286483
TI  - Lifetime physical activity and breast cancer risk in the Shanghai Breast Cancer
      Study.
AB  - Overall physical activity in adolescence and adulthood, and changes in activity
      over the lifespan were analysed by in-person interviews among 1459 women newly
      diagnosed with breast cancer and 1556 age-matched controls in urban Shanghai.
      Physical activity from exercise and sports, household, and transportation
      (walking and cycling) was assessed in adolescence (13-19 y) and adulthood (last
      10 y), as was lifetime occupational activity. Logistic regression was used to
      estimate odds ratios (OR) and 95% confidence limits (OR (95% CL)) while
      controlling for confounders. Risk was reduced for exercise only in adolescence
      (OR = 0.84 (0.70-1.00)); exercise only in adulthood (OR = 0.68 (0.53-0.88)), and
      was further reduced for exercise in both adolescence and adulthood (OR = 0.47
      (0.36-0.62)). Graded reductions in risk were noted with increasing years of
      exercise participation (OR(1-5 yrs)= 0.81 (0.67-0.94); OR(6-10 yrs)= 0.74 (0.59
      0.93); OR(11-15 yrs)= 0.55 (0.38-0.79); OR(16 + yrs)= 0.40 (0.27-0.60);P(trend,)<
      0.01). Lifetime occupational activity also was inversely related to risk
      (P(trend)< 0.01). These findings demonstrate that consistently high activity
      levels throughout life reduce breast cancer risk. Furthermore, they suggest that
      women may reduce their risk by increasing their activity levels in adulthood.

PMID- 11286484
TI  - Paternal occupational contact level and childhood leukaemia in rural Scotland: a
      case-control study.
AB  - In a national Scottish study of 809 cases of leukaemia and non-Hodgkins lymphoma
      diagnosed in 1950-89 among children aged 0-4 years who were born in Scotland,
      together with 2363 matched population controls, we investigated one aspect of the
      infective hypothesis. This concerns whether in rural areas (where the prevalence
      of susceptible individuals is likely to be higher) the risk is greater among the
      young children of men whose work involves contacts with many different people,
      particularly children, as noted in certain childhood infections. A positive trend
      was found in rural areas across 3 levels of increasing paternal occupational
      contact (as recorded at birth) by each of 2 previously defined classifications;
      no such effect was found in urban areas. The rural trend was more marked in that
      part of the study period with greater population mixing, but the difference from
      the period with less mixing was not itself significant, leaving open whether
      these rural findings reflect the extreme isolation of much of rural Scotland, or
      the effects in such areas of a degree of population mixing. In marked contrast,
      among the 850 cases and 2492 controls aged 5-14, those in rural areas in the
      higher population mixing period showed a significantly decreasing trend with
      increasing paternal occupational contact level. This would be consistent with
      immunity produced either by earlier infection at ages 0-4 years, or directly by
      low doses of the infective agent that were largely immunizing at these older
      ages. The findings overall provide further support for infection underlying
      childhood leukaemia and for the role of adults.

PMID- 11286486
TI  - An algorithm for constructing local regions in a phylogenetic network.
AB  - The groupings of taxa in a phylogenetic tree cannot represent all the conflicting
      signals that usually occur among site patterns in aligned homologous genetic
      sequences. Hence a tree-building program must compromise by reporting a subset of
      the patterns, using some discriminatory criterion. Thus, in the worst case, out
      of possibly a large number of equally good trees, only an arbitrarily chosen tree
      might be reported by the tree-building program as "The Tree." This tree might
      then be used as a basis for phylogenetic conclusions. One strategy to represent
      conflicting patterns in the data is to construct a network. The Buneman graph is
      a theoretically very attractive example of such a network. In particular, a
      characterization for when this network will be a tree is known. Also the Buneman
      graph contains each of the most parsimonious trees indicated by the data. In this
      paper we describe a new method for constructing the Buneman graph that can be
      used for a generalization of Hadamard conjugation to networks. This new method
      differs from previous methods by allowing us to focus on local regions of the
      graph without having to first construct the full graph. The construction is
      illustrated by an example.

PMID- 11286487
TI  - Phylogeny of the genus Chironomus (Diptera) inferred from DNA sequences of
      mitochondrial cytochrome b and cytochrome oxidase I.
AB  - Two mitochondrial genes, Cytochrome b (Cytb) and Cytochrome c oxidase subunit I
      (COI), have been used as phylogenetic markers in Chironomids. The nucleotide
      sequences of 685 bp from Cytb and 596 bp from COI have been determined for 36
      Chironomus species from the Palearctic, or Holarctic, and Australasia. The
      concatenated sequence of 1281 bp from both genes was used to investigate the
      phylogenetic relationships among these species. The nucleotide sequence
      alignments were used for construction of phylogenetic trees based on maximum
      parsimony and neighbor-joining methods. Both techniques produced similar
      phylogenies. Monophyly of the genus Chironomus is supported by a bootstrap value
      of 100% at the basal branch. Six clusters of species have been revealed with high
      bootstrap values supporting both monophyly of each cluster and the validity of
      the branching order within each cluster. Four species, C. circumdatus, C.
      nepeanensis, C. dorsalis, and C. crassiforceps, cannot be placed into any
      cluster. Cytological phylogenies were constructed using the same set of species,
      except for C. biwaprimus. These trees showed many similarities to that obtained
      from the mitochondrial (mt) sequence analysis, but also a number of significant
      differences. When compared with the tree constructed from the sequence of 23
      species available for one of the globin genes, globin 2b (gb2b), there was better
      support for the mt tree than for the cytological trees. An intron, which varies
      in its occurrence and position in gb2b, was also investigated and the
      distribution of the introns supports the phylogenetic history of the genus
      Chironomus obtained with mt data. The differences observed in the cytological
      trees seem to be attributable more to the retention of the same chromosome
      banding sequence across several species, rather than convergent evolutionary
      events. An important question is the determination of the position of the
      subgenus Camptochironomus in relation to the representatives of the nominal
      subgenus Chironomus, since it has been suggested that this is a separate genus.
      The Camptochironomus species are internal to the trees and have arisen more
      recently than some of the species of the subgenus Chironomus, indicating that
      they are not sufficiently differentiated to be considered more than a subgenus.

PMID- 11286489
TI  - Phylogenetic relationships of the five extant Rhinoceros species (Rhinocerotidae,
      Perissodactyla) based on mitochondrial cytochrome b and 12S rRNA genes.
AB  - A major question in rhinocerotid phylogenetics concerns the position of the
      Sumatran rhinoceros (Dicerorhinus sumatrensis) with regard to the other extant
      Asian (Rhinoceros unicornis and R. sondaicus) and African (Diceros bicornis and
      Ceratotherium simum) species. We have examined this particular question through
      the phylogenetic analysis of the complete sequences of the mitochondrial 12S rRNA
      and cytochrome b genes. Three additional perissodactyls (one tapir and two
      equids) plus several outgroup cetartiodactyls were included in the analysis. The
      analysis identified a basal rhinocerotid divergence between the African and the
      Asian species, with the Sumatran rhinoceros forming the sister group of the genus
      Rhinoceros. We estimate the Asian and African lineages to have diverged at about
      26 million years before present.

PMID- 11286488
TI  - Partial combination applied to phylogeny of European cyprinids using the
      mitochondrial control region.
AB  - Previous molecular phylogenies of European cyprinids led to some solid facts and
      some uncertainties. This study is based on a stretch of more than 1 kb in the
      mitochondrial control region newly sequenced for 35 European cyprinids and on
      previous cytochrome b and 16S rDNA data. The trees based on the control region
      are more accurate and robust than those obtained from the two other genes.
      Character incongruence among the three genes was tested using the incongruence
      length difference (ILD) test. Iterative removals of individual sequences followed
      by new ILD tests identified two sequences responsible for statistically
      significant incongruence. A partial combination was conducted, that is, a
      combination of the three data sets, removing the two sequences previously
      identified. The phylogenetic analysis of this partial combination gives a more
      robust and resolved picture of subfamilial interrelationships. The Rasborinae are
      the sister group of all other cyprinids. The monophyletic Cyprininae emerges
      next. Tinca tinca first and then Rhodeus are the sister groups of all the
      remaining nonrasborine and noncyprinine species. Gobio is the sister group of the
      Leuciscinae, in which the Phoxinini are the sister group of the Leuciscini.
      Within the Leuciscini, the genus Leuciscus and the subfamily Alburninae are both
      paraphyletic. The Rasborinae are the most basal cyprinid subfamily and the
      Tincinae are not the sister group of the Cyprininae. These two results challenge
      only two anatomical characters, which need to be reinterpreted or considered as
      homoplastic in cyprinid evolution: the modification of the first pleural rib and
      its parapophysis and the bony composition of the interorbital septum.

PMID- 11286490
TI  - Molecular phylogeny of the lemur family cheirogaleidae (primates) based on
      mitochondrial DNA sequences.
AB  - Cheirogaleidae currently comprises five genera whose relationships remain
      contentious. The taxonomic status and phylogenetic position of both Mirza
      coquereli and Allocebus trichotis are still unclear. The taxonomic status of the
      recently discovered Microcebus ravelobensis (a sympatric sibling species of
      Microcebus murinus) and its phylogenetic position also require further
      examination. A approximately 2.4-kb mitochondrial DNA sequence including part of
      the COIII gene, complete ND3, ND4L, and ND4 genes, and 5 tRNAs was used to
      clarify relationships among cheirogaleids. Mirza and Microcebus form a clade
      representing the sister group of Allocebus, with a clade containing Cheirogaleus
      major and Cheirogaleus medius diverging first. M. ravelobensis and Microcebus
      rufus form a subclade within Microcebus, with M. murinus as its sister group. The
      molecular data support the generic status of Mirza coquereli and species-level
      divergence of M. ravelobensis. Furthermore, "M. rufus" may well represent more
      than one species.

PMID- 11286491
TI  - Nuclear and mtDNA phylogenies of the Trimeresurus complex: implications for the
      gene versus species tree debate.
AB  - Phylogenies based on mitochondrial DNA (mtDNA) may represent gene trees that may
      not be congruent with the equivalent species tree. One solution to this problem
      is to include additional, independent loci from the nuclear genome. Sequence data
      from the seventh intron of the beta-fibrinogen gene were generated for 25
      specimens of vipers, including 8 nominal species of the Trimeresurus complex of
      Asian pit vipers. Phylogenetic trees were generated using maximum-parsimony and
      maximum-likelihood methods. The taxonomic level at which the intron provided
      significant phylogenetic information was examined and the trees were compared to
      those produced from previously obtained mtDNA cytochrome b sequences. A variety
      of different approaches (separate analyses, conditional data combination, and
      consensus) were used in an attempt to provide a sound organismal phylogeny based
      on both nuclear and mtDNA data sets. We discuss the implications for the gene
      tree-species tree debate and its particular relevance to medically important
      organisms.

PMID- 11286492
TI  - Nuclear DNA variation in spider monkeys (Ateles).
AB  - Phylogenetic relationships based on DNA sequence variation for the aldolase A
      intron V nuclear genomic region were evaluated and compared to phylogenies based
      on mitochondrial DNA sequence variation among spider monkeys (Ateles). Samples of
      Ateles ranging from Central America throughout the Amazon Basin were sequenced to
      determine phylogenetic relationships among geographically widely distributed
      populations. Analysis of nuclear DNA sequences using parsimony, maximum
      likelihood, and genetic distance analyses produced similar phylogenies. Four
      previously proposed monophyletic species of spider monkeys were: (1) Ateles
      paniscus, composed of haplotypes from the northeastern Amazon Basin; (2) A.
      belzebuth, found in the western and southern Amazon Basin; (3) A. hybridus,
      located primarily along the Magdalena River valley of Colombia; and (4) A.
      geoffroyi, including all haplotypes found in the Choco region of South America
      and throughout Central America. The nuclear phylograms were analyzed based on
      associated bootstrap support and confidence probabilities. Support from the
      nuclear DNA genome was less robust than support from the mitochondrial DNA data,
      most likely due to a level of sequence variation, which was 90% less than that of
      the mitochondrial DNA genome. Nuclear DNA congruencies with mitochondrial DNA
      based phylogenies, as supported by the incongruence length difference and winning
      sites tests, provide further support for the suggested revisions in Ateles
      taxonomy that are contradictory to long-held taxonomies based on pelage
      variation.

PMID- 11286493
TI  - Phylogenetic utility of the major opsin in bees (Hymenoptera: Apoidea): a
      reassessment.
AB  - Major opsin (LW Rh) DNA sequence has been reported to provide useful data for
      resolving phylogenetic relationships among tribes of corbiculate bees based on
      analyses of 502 bp of coding sequence. However, the corbiculate tribes are
      believed to be of Cretaceous age, and strong support for insect clades of this
      age from small data sets of nucleotide sequence data has rarely been
      demonstrated. To more critically assess opsin's phylogenetic utility we generated
      an expanded LW Rh data set by sequencing the same gene fragment from 52
      additional bee species from 24 tribes and all six extant bee families. Analyses
      of this data set failed to provide substantial support for monophyly of
      corbiculate bees, for relationships among corbiculate tribes, or for most other
      well-established higher-level relationships among long-tongued bees. However,
      monophyly of nearly all genera and tribes is strongly supported, indicating that
      LW Rh provides useful phylogenetic signal at lower taxonomic levels. When our
      expanded LW Rh data set is combined with a morphological and behavioral data set
      for corbiculate bees, the results unambiguously support the traditional phylogeny
      of the corbiculate bee tribes: (Euglossini + (Bombini + (Meliponini + Apini))).
      This implies a single origin of advanced eusocial behavior among bees rather than
      dual origins, as proposed by several recent studies.

PMID- 11286494
TI  - Evolutionary relationships among the true vipers (Reptilia: Viperidae) inferred
      from mitochondrial DNA sequences.
AB  - Nucleotide sequences of mitochondrial cytochrome b and 16S rRNA genes, totaling
      946 bp, were used to reconstruct a molecular phylogeny of 42 species of the
      subfamily Viperinae representing 12 of the 13 recognized genera. Maximum
      parsimony and maximum-likelihood were used as methods for phylogeny
      reconstruction with and without a posteriori weighting. When representatives of
      the Causinae were taken as outgroup, five major monophyletic groups were
      consistently identified: Bitis, Cerastes, Echis, the Atherini (Atheris s.l.), and
      the Eurasian viperines. Proatheris was affiliated with Atheris, and Adenorhinos
      clustered within Atheris. The African Bitis consisted of at least three
      monophyletic groups: (i) the B. gabonica group, (ii) the B. caudalis group, and
      (iii) the B. cornuta group. B. worthingtoni and B. arietans are not included in
      any of these lineages. Eurasian viperines could be unambiguously devided into
      four monophyletic groups: (i) Pseudocerastes and Eristicophis, (ii) European
      vipers (Vipera s.str.), (iii) Middle East Macrovipera plus Montivipera (Vipera
      xanthina group), and (iv) North African Macrovipera plus Vipera palaestinae and
      Daboia russelii. These evolutionary lineages are consistent with historical
      biogeographical patterns. According to our analyses, the viperines originated in
      the Oligocene in Africa and successively underwent a first radiation leading to
      the five basal groups. The radiation might have been driven by the possession of
      an effective venom apparatus and a foraging startegy (sit-wait-strike) superior
      in most African biomes and might have been adaptive. The next diversifications
      led to the Proatheris-Atheris furcation, the basal Bitis splitting, and the
      emergence of the basal lineages within the Eurasian stock. Thereafter, lineages
      within Echis, Atheris, and Cerastes evolved. The emergence of three groups within
      Vipera s.l. might have been forced by the existence of three land masses during
      the early Miocene in the area of the Paratethys and the Mediterranean Seas.
      Taxonomic consequences of these findings are discussed.

PMID- 11286495
TI  - The phylogenetic relationships of "predatory water-fleas" (Cladocera: Onychopoda,
      Haplopoda) inferred from 12S rDNA.
AB  - Within the Cladocera, the water-fleas, four major taxa can be distinguished:
      Anomopoda, Ctenopoda, Haplopoda, and Onychopoda. Haplopoda and Onychopoda are
      called "predatory water-fleas." The Haplopoda is monotypic; its only
      representative, Leptodora kindtii, is common in palearctic and nearctic
      freshwater bodies. The Onychopoda show a remarkable geographic distribution. Most
      of the described species are restricted to the Caspian Sea, the Aral Sea, and
      peripheral areas of the Black Sea, including the Sea of Azov--all remnants of the
      Eastern Paratethys. The remaining onychopods are either freshwater inhabitants or
      marine animals, widespread in the world oceans. We present molecular evidence for
      a sister group relationship between Haplopoda and Onychopoda within the
      Cladocera. The Onychopoda and its three families are monophyletic. We suggest an
      independent invasion into the Ponto-Caspian basin at least three times, twice
      originating in the palearctic freshwater bodies and once starting from the world
      oceans.

PMID- 11286496
TI  - Molecular polytomies.
AB  - This paper focuses on polytomies, especially molecular polytomies. The
      distinction between molecular and species polytomies is important, but is often
      not made. Likelihood ratio tests are an easier method for detecting molecular
      polytomies than other methods cited herein. Simulation shows that parsimony will
      generally falsely resolve molecular polytomies, which is worrisome because a
      simple mathematical model described herein predicts that molecular polytomies
      will occur often when the mean branch length is small. A test of the model using
      several real molecular data sets indicates that molecular polytomies may actually
      occur more often than predicted by the model. This suggests that at least some
      published molecular parsimony trees contain clades that are false resolutions of
      polytomies. Finally, a possible method for detecting species polytomies from
      molecular data is described.

PMID- 11286497
TI  - On the status of the Serranid fish genus Epinephelus: evidence for paraphyly
      based upon 16S rDNA sequence.
AB  - Historically, attempts to elucidate evolutionary relationships among members of
      the genus Epinephelus (Teleostei: Serranidae), commonly known as groupers, have
      been hindered by the overwhelming number of species (98, sensu stricto), a pan
      global distribution, and the lack of morphological specializations traditionally
      used in ichthyological classification. To date, no comprehensive phylogenetic
      study, morphological or molecular, to evaluate the monophyly of this genus has
      been presented. In this study, previous hypotheses regarding the relationships
      among the American grouper species and the allied genera were evaluated by
      examination of mitochondrial DNA sequences of the 16S ribosomal DNA region. A 590
      bp region of the 16S rDNA gene was amplified using a universal primer pair for 42
      serranid species, including members of the genera Epinephelus, Mycteroperca, and
      Paranthias from the New World and selected Indo-Pacific congeners. Maximum
      parsimony criteria and neighbor-joining analysis dispute the monophyly of the
      American Epinephelus species as previously hypothesized. The data support the
      monophyly of Cephalopholis only with the inclusion of the morphologically
      distinct Paranthias and the monophyly of Mycteroperca with the inclusion of the
      Indo-Pacific Anyperodon leucogrammicus.

PMID- 11286498
TI  - Molecular phylogenetics of western North American frogs of the Rana boylii
      species group.
AB  - Phylogenetic relationships among frogs of the genus Rana from western North
      America are investigated using 2013 aligned bases of mitochondrial DNA sequence
      from the genes encoding ND1 (subunit one of NADH dehydrogenase), tRNA(Ile),
      tRNA(Gln), tRNA(Met), ND2, tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr),
      and COI (subunit I of cytochrome c oxidase), plus the origin for light-strand
      replication (O(L)) between the tRNA(Asn) and tRNA(Cys) genes. The aligned
      sequences contain 401 phylogenetically informative characters. A well-resolved
      phylogenetic hypothesis in which the Rana boylii species group (R. aurora, R.
      boylii, R. cascadae, R. muscosa, and R. pretiosa) is monophyletic is obtained.
      Molecular sequence divergence suggests that the R. boylii species group is
      approximately 8 million years old. The traditional hypothesis showing monophyly
      of the yellow-legged frogs (R. boylii and R. muscosa) is statistically rejected
      in favor of a hypothesis in which R. aurora, R. cascadae, and R. muscosa form a
      clade. Reanalyses of published nuclear ribosomal DNA restriction-site data and
      allozymic data support a monophyletic R. boylii group, but do not effectively
      resolve relationships among species within this group. Eight populations of R.
      muscosa form two major clades separated by a biogeographic break in the Sierra
      Nevada of California. This biogeographic break is broadly concordant with breaks
      found in four other amphibian and reptilian taxa. The two major clades within R.
      muscosa are estimated to have diverged approximately 2.2 million years before
      present. Each of these major clades contains two subgroups showing approximately
      1.5 million years divergence, implicating climatic effects of Pleistocene
      glaciation in vicariance. The four distinct subgroups of R. muscosa separated by
      at least 1.4 million years of evolutionary divergence are suggested as potential
      units for conservation.

PMID- 11286499
TI  - Phylogenetic relationships within Diadasia, a group of specialist bees.
AB  - We estimated phylogenetic relationships among species of the bee genus Diadasia,
      a group of new world, specialist bees. We sequenced approximately 2 kb of the
      mitochondrial genes cytochrome oxidase subunit I and II and tRNA leucine and
      approximately 1 kb of the nuclear gene elongation factor 1-alpha for 24 North
      American Diadasia species, 4 South American species, and five outgroup genera.
      Parsimony analyses of the two data sets were highly congruent. A combined
      analysis produced a well-resolved phylogenetic hypothesis that supported the
      monophyly of Diadasia, but not that of traditional subgenera: Diadasia s. str.
      was paraphyletic in all analyses. With one exception, the North and South
      American species formed separate clades, supporting previous hypotheses that two
      lineages of Diadasia have dispersed from South to North America: a more recent
      dispersal of D. ochracea and an older dispersal of the ancestor to all other
      North American species. Different species of Diadasia specialize on pollen from
      at least five different plant families; the phylogeny presented here, along with
      known host affinities, indicates that host-switching has been rare.

PMID- 11286500
TI  - The mitochondrial cytochrome oxidase II gene in Bacillus stick insects: ancestry
      of hybrids, androgenesis, and phylogenetic relationships.
AB  - Sequencing of a cytochrome oxidase II (COII) gene fragment in Bacillus taxa
      provided evidence that the bisexual B. rossius is the maternal ancestor of the
      hybridogenetic B. rossius-grandii strains and revealed the same ancestry for both
      parthenogenetic hybrids: the diploid B. whitei (B. rossius/grandii grandii) and
      the triploid B. lynceorum (B. rossius/grandii grandii/atticus). Present data
      clearly demonstrate that all Bacillus unisexuals arose through asymmetrical
      hybridization events and realized a paraphyletic derivation from the B. rossius
      redtenbacheri subspecies. The invention of B. rossius mitochondrial DNA
      haplotypes in specimens with B. grandii grandii nuclear genomes revealed the
      occurrence of androgenesis in nature. Natural androgens represent a peculiar
      escape from hybridity and can help maintain the hybridogenetic system through the
      production of the fathering taxon via hybrid females. Results from the COII gene
      support the phyletic relationships among taxa suggested by previous taxonomical
      approaches, but also indicate a departure of B. grandii subspecies from the
      established taxonomy. Assuming the existence of a molecular clock, the evaluated
      substitution rate brings the splitting between B. rossius and B. grandii/B.
      atticus back to 22.79 +/- 2.65 myr before present, while the origin of hybrids
      appears to be much more recent (1.06 +/- 0.53 myr).

PMID- 11286501
TI  - Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis
      for overgrowth, malformation, and cancer predisposition.
AB  - Simpson Golabi Behmel syndrome (SGBS) is a complex congenital overgrowth syndrome
      with features that include macroglossia, macrosomia, and renal and skeletal
      abnormalities as well as an increased risk of embryonal cancers. Most cases of
      SGBS appear to arise as a result of either deletions or point mutations within
      the glypican-3 (GPC3) gene at Xq26, one member of a multigene family encoding for
      at least six distinct glycosylphophatidylinositol-linked cell surface heparan
      sulfate proteoglycans. As a class of molecules, heparan sulfate proteoglycans
      have been found to play essential roles in development by modulating cellular
      responses to growth factors and morphogens. Specifically, mutations in both the
      murine GPC3 gene and the Drosophila glypican, dally, have been found to modify
      cellular responses to bone morphogenetic proteins, providing important clues to
      the molecular basis of SGBS in humans. Despite these advances, there remains a
      paucity of information about the natural history of SGBS and optimal medical
      management strategies, and whether select mutations influence the SGBS phenotype
      and risk of cancer. To this end, an International SGBS Registry has been created
      and is being maintained to improve the clinical care and understanding of the
      pathogenesis of SGBS. Using an integrated approach employing epidemiology,
      molecular genetic characterization of specific GPC3 mutations, and the use of
      model organisms should rapidly expand the understanding of this complex disorder.

PMID- 11286502
TI  - The role of corticotropin-releasing hormone receptors in placenta and fetal
      membranes during human pregnancy.
AB  - Corticotropin-releasing hormone (CRH) is a 41 amino acid polypeptide that exerts
      a wide spectrum of hypothalamic and extrahypothalamic functions. Moreover, the
      placenta and other intrauterine tissues produce and secrete immunoreactive CRH.
      It has been demonstrated that placental CRH is secreted into the maternal
      circulation in large amounts during the third trimester of human pregnancy and
      may play an important role in the onset of labor. CRH exerts a number of
      functions within the intratuterine environment like induction of prostaglandin
      production and maintenance of the placental blood flow. Here we present an
      overview of current knowledge about the CRH receptor subtypes and their signaling
      properties within the feto-placental unit.

PMID- 11286503
TI  - Functional analysis of the human galactose-1-phosphate uridyltransferase promoter
      in Duarte and LA variant galactosemia.
AB  - Human galactose-1-phosphate uridyltransferase (hGALT) is an evolutionarily
      conserved enzyme central to D-galactose metabolism. The impairment of hGALT
      causes galactosemia. One missense mutation, an aspartate to asparagine
      substitution at amino acid 314 (N314D), impairs 50% activity in the homozygous
      state in some patients but gives near normal activity in others. The former
      condition is called Duarte (D) and the latter, Los Angeles (LA). The D allele is
      linked to hGALT polymorphisms including a deletion 5'to the translation start
      site (-119 to -116delGTCA), g1391G --> A and g1105G --> C. The LA allele is
      linked to a g1721C --> T transition. To investigate possible mechanisms for
      differences in hGALT activity between the D and LA alleles, we sequenced 3951
      nucleotides of genomic DNA 5' to the hGALT translation start site. Using a dual
      luciferase reporter system to express deletion constructs of the hGALT promoter,
      we noted both positive and negative regulatory regions. Two putative positive
      regulatory domains overlap with the naturally occurring -119 to -116delGTCA
      linked to Duarte. One is an E-box motif (CACGTG) at -117 to -112 bp. The second
      is an AP-1 motif (TCAGTCAG) at -124 to -119 bp. The delGTCA mutation confers
      reduced luciferase activity to transfected cell lines derived from human ovarian
      and liver neoplasms. Additionally, human lymphoblasts derived from patients with
      the Duarte allele have reduced GALT mRNA. We conclude that the human GALT gene is
      regulated in the first -165 bp of its promoter region by positive regulators of
      GALT gene expression. The -119 to -116delGTCA reduces hGALT transcription
      resulting in reduced GALT activity in the Duarte allele.

PMID- 11286504
TI  - Galactose metabolism in mice with galactose-1-phosphate uridyltransferase
      deficiency: sucklings and 7-week-old animals fed a high-galactose diet.
AB  - Mice deficient in galactose-1-phosphate uridyltransferase (GALT) demonstrate
      abnormal galactose metabolism but no obvious clinical phenotype. To further
      dissect the pathways of galactose metabolism in these animals, galactose
      oxidation and metabolite levels were studied in 16-day-old sucklings and the
      effect of a 4 week prior exposure to a 40% glucose or 40% galactose diet was
      determined in 7-week-old mice. Suckling GALT-deficient (G/G) mice slowly oxidized
      [1-14C]galactose to 14CO2, 4.0% of the dose when fed and 7.9% when fasted
      compared to normal animals 38.3 and 36.4% in 4 h, respectively. Plasma of G/G
      sucklings contained 11.1 mM galactose and erythrocyte galactose 1-phosphate
      levels were 28.2 and 31.9 mg/dl packed cells. Galactose, galactitol, galactonate,
      and galactose 1-phosphate were found in G/G suckling mouse tissues. The tissue
      galactose concentrations were 10% or less of that in plasma, suggesting that
      there was limited cellular entry of galactose. In 7-week-old fasted mice with 4
      weeks prior exposure to glucose or galactose-containing diet, 4-h oxidation was
      12.9 and 15.0% of the administered radiolabeled galactose, respectively. Normal
      animals oxidized 33.9 and 37.9% of the dose when fed the same diets,
      respectively. The ability of G/G mice to oxidize galactose in the absence of GALT
      activity suggests the presence of alternate metabolic pathways for galactose
      disposition. G/G mice fed the galactose-free 40% glucose diet had erythrocyte
      galactose 1-phosphate levels ranging from 6.4 to 17.7 mg/dl packed cells and
      detectable galactose and galactose metabolites in tissues, suggesting that these
      animals endogenously produced galactose. The plasma of 40% galactose-fed G/G mice
      contained 9.1 mM galactose with red blood cell galactose 1-phosphate averaging
      43.6 mg/dl. Tissues of these animals also contained high levels of galactose and
      galactose 1-phosphate. Liver contained over 4 micromol/g galactonate but little
      galactitol. Despite the elevated galactose and galactose 1-phosphate, the animals
      tolerated the high-galactose diet and were indistinguishable from normal animals,
      exhibiting no manifestations of galactose toxicity seen in human GALT-deficient
      galactosemia. The data suggest that high galactose 1-phosphate levels do not
      cause galactose toxicity and that high galactitol in combination with galactose 1
      phosphate may be a prerequisite. Absence of GALT appears necessary but
      insufficient to produce human galactosemic phenotype.

PMID- 11286505
TI  - Evidence for alternate galactose oxidation in a patient with deletion of the
      galactose-1-phosphate uridyltransferase gene.
AB  - The persistent, dietary-independent elevation of galactose metabolites in
      patients with galactose-1-phosphate uridyltransferase (GALT) deficiency is
      probably secondary to de novo synthesis of galactose. Relatively constant steady
      state levels of galactose metabolites in patients also suggest that non-GALT
      metabolic pathways must function to dispose of the galactose synthesized each
      day. The discovery of a patient with a rare deletion of the GALT gene provided a
      unique opportunity to examine the availability of any alternate galactose
      oxidative capacity both in vivo and in vitro. Utilizing genomic DNA from the
      patient, Southern blot data demonstrated that 10 of the 11 GALT exons were
      homozygously deleted. By measurement of 13CO2 in expired air for up to 24 h after
      an oral bolus of [1-13C]galactose, it was demonstrated that 17% of the galactose
      was metabolized, a value comparable to the 3-h elimination rate in a control
      subject. Furthermore, lymphoblasts prepared from the patient could also convert
      [1-14C]galactose to 14CO2. This unique study provides the first unambiguous
      evidence that another pathway exists in man that can be responsible for galactose
      disposal. Further knowledge of this alternate galactose oxidative route and its
      regulation may aid in formulating new strategies for the treatment of
      galactosemia.

PMID- 11286506
TI  - Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a
      novel T-protein mutation (N145I): a strategy for the molecular investigation of
      patients with nonketotic hyperglycinemia (NKH).
AB  - Screening a DNA bank from 50 patients with enzymatic confirmation of their
      diagnosis of nonketotic hyperglycinemia gave allele frequencies of 5% for R515S
      of P-protein (glycine decarboxylase) and 7% for R320H of T-protein
      (aminomethyltransferase). In a previous report we found that 3% of the same
      patient alleles were positive for T-protein IVS7-1G>A. In total, testing for
      these three mutations identified 15% of alleles and positive results (one or two
      mutations) were found in 11 of the 50 patients. In addition, a novel point
      mutation in T-protein, N145I, was found in a single case and a PCR/restriction
      enzyme assay was developed for its detection.

PMID- 11286507
TI  - G76E substitution in type I collagen is the first nonlethal glutamic acid
      substitution in the alpha1(I) chain and alters folding of the N-terminal end of
      the helix.
AB  - The majority of osteogenesis imperfecta (OI) is caused by substitutions for
      glycine residues in the two alpha chains of type I collagen. Since only 4% of
      possible nucleotide changes in type I collagen glycine codons would result in a
      glutamic acid substitution, these are predicted to be infrequent. Only one
      glutamic acid substitution in type I collagen has been fully reported. We
      describe here the clinical, biochemical, and molecular characterization of a girl
      with severe type III OI caused by a G76E substitution in COL1A1. This is the
      first delineation of a glutamic acid substitution in the alpha1(I) chain causing
      nonlethal osteogenesis imperfecta. The proband's fibroblast type I collagen
      chains and cyanogen bromide peptides were electrophoretically normal, while
      osteoblast collagen was slightly overmodified. This suggested a mutation near the
      N-terminal end of the collagen helix. A mismatch was detected by RNA:DNA hybrid
      analysis in cDNA coding for 106 amino acids at the N-terminal end of the helical
      region. Subclones of both alleles were sequenced and revealed a G --> A (c.761G >
      A) mutation causing an alpha1(I) G76E substitution in one allele. The presence of
      the mutation in the proband's leukocyte gDNA, and its absence in parental gDNA,
      was confirmed by Tsp509I digestion. The glutamic acid substitution alters the
      folding of the mutant collagen helices. Pericellular processing of type I
      collagen by the proband's fibroblasts yielded an earlier appearance of the pC
      alpha1(I) form and of mature alpha chains as compared to control cell processing.
      Also, the presence of the glutamic acid substitution apparently exposes the
      adjacent Arg75 residue in the alpha1 chain. Trypsin digestion of proband
      fibroblast collagen resulted in shortened alpha1 chains, as confirmed by CNBr
      analysis. In addition, the Tm for mutant helices from fibroblasts and osteoblasts
      was decreased 2-4 degrees C versus controls, demonstrating a decrease in helix
      stability. These findings increase our understanding of the disruptive effect of
      glutamic acid substitutions in collagen.

PMID- 11286508
TI  - Identification of the alpha-aminoadipic semialdehyde dehydrogenase
      phosphopantetheinyl transferase gene, the human ortholog of the yeast LYS5 gene.
AB  - In mammals, L-lysine is first catabolized to alpha-aminoadipate semialdehyde by
      the bifunctional enzyme alpha-aminoadipate semialdehyde synthase (AASS), followed
      by a conversion to alpha-aminoadipate by alpha-aminoadipate semialdehyde
      dehydrogenase. In Saccharomyces cerevisiae, which synthesize rather than degrade
      lysine, the latter activity requires two distinct genes. LYS2 encodes the alpha
      aminoadipate reductase activity, while LYS5 encodes a phosphopantetheinyl
      transferase activity that is required to activate Lys2p. We have identified a
      full-length human cDNA homologous to the yeast LYS5 gene. The cDNA contains an
      open-reading frame of 930 bp predicted to encode 309 amino acids, and the human
      protein is 26% identical and 44% similar to its yeast counterpart. In Northern
      blot analysis the cDNA hybridizes to a single transcript of approximately 3 kb in
      all tissues except testis, where there is an additional transcript of 1.5 kb.
      Expression is highest in brain followed by heart and skeletal muscle, and to a
      lesser extent in liver. We further identified three human genomic BAC clones
      containing the human gene. Fluorescence in situ hybridization (FISH) analysis
      using the BAC clones mapped the gene to chromosome 11q22 while alignment of the
      cDNA and genomic sequences allowed partial identification of the intron-exon
      boundaries. Finally, using one-step homologous recombination in S. cerevisiae we
      generated a lys5 knockout strain. Complementation studies in the yeast knockout
      demonstrate that the human homolog encodes alpha-aminoadipate dehydrogenase
      phosphopantetheinyl transferase activity. We hypothesize that defects in this
      gene may result in pipecolic acidemia.

PMID- 11286509
TI  - Identification of a human brain-specific gene, calneuron 1, a new member of the
      calmodulin superfamily.
AB  - The calmodulin superfamily includes the calmodulins, calcium-binding proteins,
      and related genes. Herein, we describe the cloning and characterization of human
      calneuron 1 (CALN1). CALN1 encodes a novel neuron-specific protein that maps to
      chromosome 7q11. CALN1 spans a large genomic region (>360 kb). Sequence
      comparison shows significant similarity with the calmodulin superfamily of genes,
      especially in the two conserved EF-hand motifs. The mouse orthologous gene
      (Caln1) shows little prenatal expression, with highest expression at Postnatal
      Day 21. In situ hybridization to adult mouse brain shows high expression in the
      cerebellum, hippocampus, and cortex. The high expression of this gene exclusively
      in brain, the developmental changes in expression levels, the high homology with
      calmodulin which indicates a potential role in signal transduction, and the
      cellular localization of the mRNA suggest that CALN1 has a significant role in
      the physiology of neurons and is potentially important in memory and learning.

PMID- 11286510
TI  - Long-term treatment with sodium phenylbutyrate in ornithine transcarbamylase
      deficient patients.
AB  - Ornithine transcarbamylase deficiency is a very heterogeneous urea cycle disorder
      resulting in hyperammonemia with various presentations from the neonatal period
      through adulthood. We performed a retrospective study in nine patients (four
      male/five female, age at diagnosis ranging from 6 days to 14 years) to evaluate
      the safety and efficacy of sodium phenylbutyrate (Ammonaps) in long-term
      treatment. All patients were diagnosed by DNA mutational analysis and/or liver
      enzyme measurement. They had previously been treated with sodium benzoate (median
      dose 248 mg/kg/day; range 106-275) and low protein diet (median 0.84 g/kg/day)
      and were switched to sodium phenylbutyrate (median dose of 352 mg/kg/day) at 8.9
      and 4.9 years of age (median) in males and females, respectively. We analyzed
      clinical and biochemical data and the median follow-up duration was 26 months.
      During that time, there were no hyperammonemic episodes requiring
      hospitalization. Median plasma ammonia and glutamine levels were 30 and 902
      micromol/L, respectively. Total protein intake could be increased to 0.95
      g/kg/day after 18 months. No side effects related to therapy were observed.
      Further prospective studies should be performed to define the optimal dosage of
      sodium phenylbutyrate and the requirements for protein diet at different ages.

PMID- 11286511
TI  - Linkage studies of SOX13, the ICA12 autoantigen gene, in families with type 1
      diabetes.
AB  - SOX13 is a member of the SOX family of transcription factors that encodes the
      type 1 diabetes autoantigen, ICA12. The SOX13 gene maps at chromosome 1q31.3-32.1
      near a region containing a susceptibility locus for type 1 diabetes. SOX13 was
      assessed as a candidate susceptibility gene. Analysis of the SOX13 gene
      identified a number of single nucleotide polymorphisms and a polymorphic CA
      dinucleotide repeat. Linkage and association studies indicate that SOX13 is
      unlikely to make a substantial contribution to type 1 diabetes susceptibility.

PMID- 11286512
TI  - Analysis of slc19a2, on 1q23.3 encoding a thiamine transporter as a candidate
      gene for type 2 diabetes mellitus in pima indians.
AB  - Mutations in the SLC19A2 gene cause thiamine-responsive megaloblastic anemia
      (TRMA) frequently combined with diabetes mellitus and deafness. Type 2 diabetes
      mellitus is heritable and a region on 1q21-q23 encompassing SLC19A2 was linked
      with the disease in Pima Indians and Caucasians. We therefore investigated this
      candidate gene in selected diabetic and nondiabetic Pimas and found no variants.
      We conclude that mutations in SLC19A2 do not contribute to type 2 diabetes in
      this population.

PMID- 11286515
TI  - Coronary revascularization, when it needs to be done it needs to be done.

PMID- 11286516
TI  - Increased QT dispersion with the D-allele of the ACE polymorphism.

PMID- 11286517
TI  - Radioactive stents to reduce restenosis: time for an epitaph?

PMID- 11286518
TI  - The heart failure epidemic: exactly how big is it?

PMID- 11286519
TI  - How do you measure exercise capacity in chronic heart failure?

PMID- 11286520
TI  - Intracoronary radiation therapy.

PMID- 11286521
TI  - 'It all used to be so simple in the old days'; a personal view.

PMID- 11286522
TI  - The consequences of under-use of coronary revascularization; results of a cohort
      study in Northern Italy.
AB  - AIM: To assess whether under-use of coronary artery bypass graft (CABG) or
      percutaneous transluminal coronary angioplasty (PTCA) affects patient outcome.
      PATIENTS AND METHODS: A prospective observational study was performed following
      up a cohort of patients, candidates for a revascularization procedure (either
      CABG or PTCA) after an index angiogram. A total of 1258 patients, candidates --
      according to explicit criteria -- for either CABG or PTCA entered the study
      enrolled by 16 hospitals located in a Northern Italian region (Lombardia).
      Information on demographic and clinical characteristics, type of care received
      (i.e. CABG or PTCA performed Yes/No) and vital status was obtained from
      revascularization laboratories, patients' hospital medical records and local
      census offices of the town of patients' residence. The main outcome measure was
      total unadjusted and adjusted mortality at a minimum follow-up of 9 months after
      the index cardiac angiogram. RESULTS: Patients who received CABG or PTCA (n=863)
      had lower mortality than those who did not (n=350) (4.8% vs 10.6%, P=0.001). This
      held true after adjustment for relevant risk factors between the two groups such
      as extent of coronary artery disease, clinical symptoms, and cardiac surgical
      risk index (adjusted odds ratio=0.48; 95% confidence intervals=0.30--0.77) and
      after performing a survival analysis (adjusted hazard ratio=0.31; 95% confidence
      intervals=0.19--0.50). CONCLUSIONS: Failure to perform a revascularization
      procedure when it was indicated led, in this study, to a significantly increased
      mortality showing that under-use of effective procedures may represent a
      significant quality of care problem even in areas where health care systems are
      well developed. Although the study was not specifically designed to identify
      determinants of under-use (i.e. reduced capacity leading to waiting lists,
      physicians' competence or patients' refusal to undergo a recommended procedure)
      our data suggest that limited capacity could have been the most important reason.
      Our findings also provide further evidence of the validity of the RAND method to
      assess the impact of under-use of coronary revascularization procedures.

PMID- 11286523
TI  - The D-allele of the ACE polymorphism is related to increased QT dispersion in 609
      patients after myocardial infarction.
AB  - AIMS: Prolongation of QT dispersion can be observed in some patients with
      myocardial infarction and serves as a possible independent risk factor for sudden
      cardiac death. Angiotensin-converting enzyme (ACE) inhibition has been shown to
      reduce QT dispersion in myocardial infarction patients. We hypothesized that ACE
      gene I/D polymorphism, which is known to modulate ACE activity, may also affect
      QT dispersion after myocardial infarction. METHODS AND RESULTS: We studied 609
      myocardial infarction patients (532 men, aged 56.1+/-0.3; mean 5.5 years after
      myocardial infarction) from a population-based myocardial infarction register by
      standardized questionnaire, anthropometry, ECG, echocardiography, and genotyping
      of ACE I/D polymorphism. In addition, 540 unaffected siblings (251 men, age
      54.6+/-0.4 years) of these patients were studied by the same protocol. As
      compared with their healthy siblings, mean QT dispersion was prolonged in
      myocardial infarction patients (65.9+/-1.4 ms vs 91.2+/-2.3 ms, respectively,
      P<0.001). QT dispersion was negatively correlated to left ventricular ejection
      fraction (P<0.005). The ACE DD-genotype was associated with longer QT dispersion
      in myocardial infarction patients (103.0+/-4.6 ms vs 81.9+/-4.5 ms in the II
      group, P<0.001). This association was noted to be strong in multivariate analyses
      that included age, gender, ejection fraction, left ventricular end-diastolic
      diameter, medication, and heart rate. In contrast, no association between the ACE
      DD-genotype and QT dispersion was detected in healthy siblings of myocardial
      infarction patients. CONCLUSION: Thus, the ACE D-allele may be associated with
      increased QT dispersion in patients after myocardial infarction but not in
      healthy subjects. An interaction of myocardial damage and genetic predisposition
      that both enhance the activity of the renin angiotensin system may decrease the
      repolarization homogeneity of the heart.

PMID- 11286524
TI  - Clinical and angiographical follow-up after implantation of a 6--12 microCi
      radioactive stent in patients with coronary artery disease.
AB  - AIMS: This study is the contribution by the Thoraxcenter, Rotterdam, to the
      European(32)P Dose Response Trial, a non-randomized multicentre trial to evaluate
      the safety and efficacy of the radioactive Isostent in patients with single
      coronary artery disease. METHODS AND RESULTS: The radioactivity of the stent at
      implantation was 6--12 microCi. All patients received aspirin indefinitely and
      either ticlopidine or clopidogrel for 3 months. Quantitative coronary angiography
      measurements of both the stent area and the target lesion (stent area and up to 5
      mm proximal and distal to the stent edges) were performed pre- and post-procedure
      and at the 5-month follow-up. Forty-two radioactive stents were implanted in 40
      patients. Treated vessels were the left anterior descending coronary artery
      (n=20), right coronary artery (n=10) or left circumflex artery (n=10). Eight
      patients received additional non-radioactive stents. Lesion length measured 10+/
      3 mm with a reference diameter of 3.07+/-0.69 mm. Minimal lumen diameter
      increased from 0.98+/-0.53 mm pre-procedure to 2.29+/-0.52 mm (target lesion) and
      2.57+/-0.44 mm (stent area) post-procedure. There was one procedural non-Q wave
      myocardial infarction, due to transient thrombotic closure. Thirty-six patients
      returned for angiographical follow-up. Two patients had a total occlusion
      proximal to the radioactive stent. Of the patent vessels, none had in-stent
      restenosis. Edge restenosis was observed in 44%, occurring predominantly at the
      proximal edge. Target lesion revascularization was performed in 10 patients and
      target vessel revascularization in one patient. No additional clinical end-points
      occurred during follow-up. The minimal lumen diameter at follow-up averaged
      1.66+/-0.71 mm (target lesion) and 2.12+/-0.72 (stent area); therefore late loss
      was 0.63+/-0.69 (target lesion) and 0.46+/-0.76 (stent area), resulting in a late
      loss index of 0.65+/-1.15 (target lesion) and 0.30+/-0.53 (stent area).
      CONCLUSION: These results indicate that the use of radioactive stents is safe and
      feasible, however, the high incidence of edge restenosis makes this technique
      currently clinically non-applicable.

PMID- 11286525
TI  - Left ventricular systolic dysfunction in 75-year-old men and women; a population
      based study.
AB  - AIMS: To determine the prevalence of left ventricular systolic dysfunction in 75
      year-old men and women. METHODS AND RESULTS: In a population-based random sample
      of 75-year-old subjects (n=433; response rate 70.1%) the left ventricular
      systolic function was determined using two echocardiographic methods: (1) wall
      motion in nine left ventricular segments was visually scored and wall motion
      index was calculated as the mean value of the nine segments and (2) ejection
      fraction as measured by the disc summation method. Presence of heart failure was
      determined by a cardiologist's clinical evaluation. Wall motion index was
      achievable in 95% of the participants while ejection fraction was measurable in
      65%. Normal values were obtained from a healthy subgroup (n=108) and left
      ventricular systolic dysfunction was defined as the 0.5th percentile of the wall
      motion index (i.e. <1.7). In participants in whom both ejection fraction and wall
      motion index were achievable, wall motion index <1.7 predicted ejection fraction
      <43% with a sensitivity and specificity of 84.0% and 99.6%, respectively. The
      prevalence of left ventricular systolic dysfunction was 6.8% (95% CI, 5.6--8.0%)
      and was greater in men than in women (10.2% vs 3.4%, P=0.006). Clinical evidence
      of heart failure was absent in 46% of the participants with left ventricular
      systolic dysfunction. CONCLUSIONS: Left ventricular systolic dysfunction is
      common among 75-year-olds with a prevalence of 6.8% in our estimate. The
      condition is more likely to affect men than women. In nearly half of 75-year-olds
      with left ventricular systolic dysfunction there is no clinical evidence of heart
      failure.

PMID- 11286526
TI  - Assessing the effect of exercise training in men with heart failure; comparison
      of maximal, submaximal and endurance exercise protocols.
AB  - AIMS: No consensus exists regarding the most appropriate exercise testing
      protocol for patients with congestive heart failure. This study describes the
      effect of exercise training on performance using three different protocols
      (maximal, submaximal and endurance testing) in patients with heart failure.
      METHODS AND RESULTS: Thirty men (mean age 67+/-8 years) with congestive heart
      failure in NYHA class III (mean ejection fraction 32+/-5%) were evaluated prior
      to and following exercise training. A maximal exercise cycle test with gas
      exchange measurements, a submaximal 6 min walk test and an endurance treadmill
      test with blood lactate sampling were used to evaluate exercise capacity after 12
      weeks of exercise training. There was a 44.6% (P<0.001) increase in work
      performed during the maximal cycle test, with no significant increase in peak
      VO(2). The distance covered by the submaximal 6 min walk test increased by 8.1%
      (P<0.001). Lactate measured as area under the curve during the matched work
      intensity treadmill endurance test was reduced by 19.5% (P<0.005). CONCLUSION: We
      demonstrated a significant improvement in maximal, submaximal and endurance
      exercise capacity following 12 weeks of exercise training in patients with
      congestive heart failure. Endurance tests may be more sensitive and appropriate
      when assessing the efficacy of intervention in this population. Specifically,
      demonstration of reduced lactate production at matched work intensities suggests
      more efficient work and decreased dependence on anaerobic metabolism following
      training. Although maximal cycle tests are commonly used in clinical work,
      submaximal and endurance testing might be preferable for evaluating new treatment
      regimens in this population as they are easy to perform, are reproducible, and
      reflect daily tasks better than the maximal cycle test in this population.

PMID- 11286527
TI  - Trends in hospital activity, morbidity and case fatality related to atrial
      fibrillation in Scotland, 1986--1996.
AB  - AIMS: Atrial fibrillation is a common and important cause of cardiovascular
      morbidity and mortality that may become more prevalent due to an ageing
      population and more prolonged exposure to predisposing cardiovascular disease
      states. This study examines recent trends in hospitalizations related to atrial
      fibrillation in Scotland. METHODS AND RESULTS: Scotland (population 5.1 million)
      has a well described system for recording hospitalization data. All hospital
      discharges (and death) can be linked for each individual patient. We examined the
      period 1986--1996, during which time a total of 103,085 hospitalizations with a
      principal or secondary diagnosis of atrial fibrillation were recorded. The number
      of hospitalizations with a principal diagnosis of atrial fibrillation increased
      threefold from 1869 in 1986 to 5757 in 1996; the number with a secondary
      diagnosis rose from 3577 to 11,522. Similar increases were seen in the number of
      patients hospitalized, in those having a 'first-ever' hospitalization and in
      population hospitalization rates overall. The average age of patients rose, in
      men from 63.8 (SD 13.2) to 65.0 (13.2) years and in women from 72.2 (12.2) to
      73.2 (11.4) years. The proportion of those aged >75 years rose from 33% to 35% in
      men and from 56% to 60% in women. Average length of stay and case fatality fell
      during this period, but, because of the overall increase in hospitalizations,
      atrial fibrillation contributed to a growing proportion of cardiovascular-related
      bed-days utilized (from 18% to 37% with atrial fibrillation coded in any
      diagnostic position). CONCLUSION: The number of hospitalizations for atrial
      fibrillation has increased dramatically (two- to threefold) in recent years.
      These findings may be due to a real increase in atrial fibrillation prevalence,
      changing medical practice (e.g. coding or admission thresholds) or both.
      Consequently, the public health burden of atrial fibrillation is enormous.
      Moreover, the observed increase in atrial fibrillation-related hospital activity
      shows no sign of abating.

PMID- 11286528
TI  - New normal limits for the paediatric electrocardiogram.
AB  - AIMS: Previous studies that determined the normal limits for the paediatric ECG
      had their imperfections: ECGs were recorded at a relatively low sampling rate,
      ECG measurements were conducted manually, or normal limits were presented for
      only a limited set of parameters. The aim of this study was to establish an up-to
      date and complete set of clinically relevant normal limits for the paediatric
      ECG. METHODS AND RESULTS: ECGs from 1912 healthy Dutch children (age 11 days to
      16 years) were recorded at a sampling rate of 1200 Hz. The digitally stored ECGs
      were analysed using a well-validated ECG computer program. The normal limits of
      all clinically relevant ECG measurements were determined for nine age groups.
      Clinically significant differences were shown to exist, compared with previously
      established normal limits. Sex differences could be demonstrated for QRS duration
      and several amplitude measurements. CONCLUSIONS: These new normal limits differ
      substantially from those commonly used and suggest that diagnostic criteria for
      the paediatric ECG should be adjusted.

PMID- 11286529
TI  - Use of low-molecular-weight heparin as bridge anticoagulation therapy in patients
      with atrial fibrillation undergoing transoesophageal echocardiography guided
      cardioversion.

PMID- 11286530
TI  - Acute stress and ventricular arrhythmias.

PMID- 11286531
TI  - The wider use of magnesium.

PMID- 11286532
TI  - Normalized left ventricular torsion to area loops are almost equal for controls
      and aortic valve stenosis patients.

PMID- 11286533
TI  - Socioeconomic inequalities in cardiovascular disease mortality.

PMID- 11286536
TI  - Gene therapy for tolerance and autoimmunity: soon to be fulfilled promises?

PMID- 11286537
TI  - The neutrophil: function and regulation in innate and humoral immunity.
AB  - The neutrophil is a critical effector cell in humoral and innate immunity and
      plays vital roles in phagocytosis and bacterial killing. Discussed here are the
      neutrophil components necessary for these processes and the diseases in which
      these components are either lacking or dysfunctional, illustrating that normal
      neutrophil function is vital for health.

PMID- 11286538
TI  - The B cell superantigen-like interaction of intravenous immunoglobin (IVIG) with
      Fab fragments of V(H) 3-23 and 3-30/3-30.5 germline gene origin cloned from a
      patient with Kawasaki disease is enhanced after IVIG therapy.
AB  - The etiology of Kawasaki disease (KD) is still unknown. Therefore, the diagnosis
      relies on clinical criteria only. Although a specific therapy for KD is not
      available, coronary complications can be significantly reduced with the help of
      intravenous immunoglobulin (IVIG) therapy. It is not clear how IVIG interacts
      with the immune system. Previously, we selected a large number of IgG and IgM Fab
      fragments specifically reacting with IVIG molecules by phage display and
      antiidiotypic panning from three patients with autoimmune thrombocytopenia, a
      patient with lupus, and a healthy individual. Sequencing revealed that the
      favored V(H) germline gene segments of these IVIG-bound Fabs were 3-23 or 3-30/3
      30.5, the most frequently rearranged V(H) genes among human B cells. The binding
      pattern suggested a B cell superantigen-like, specific interaction of an IVIG
      subset with B cells that present B cell receptors derived from these two germline
      genes. The aim of the current study was to investigate whether treatment with
      IVIG influences this restricted interaction. Therefore we cloned and selected Fab
      fragments from a patient with KD before and after IVIG therapy. A favored
      selection of antibodies derived from both the 3-23 and the 3-30/3-30.5 germline
      gene segments as before was observed. Importantly, the reactivity with IVIG was
      significantly higher for clones from the library prepared after the IVIG
      treatment, providing the first in vivo functional evidence that a subset of IVIG
      may selectively activate B cells of this germline origin. This mechanism may add
      to the therapeutic effect of IVIG in the treatment of KD.

PMID- 11286539
TI  - Immunotherapy of HIV-infected patients with intermittent interleukin-2: effects
      of cycle frequency and cycle duration on degree of CD4(+) T-lymphocyte expansion.
AB  - The ability of IL-2 to induce expansion of the CD4(+) T lymphocyte pool has made
      it the most studied cytokine in the treatment of HIV infection. The majority of
      trials have used an empirical regimen of 5-day IL-2 cycles given every 8 weeks--a
      regimen based upon early pharmacodynamic studies and patient preference. To
      better define optimal duration and frequency of cycles, a randomized trial was
      conducted in which patients who received this "standard" regimen were compared to
      patients who received cycles of variable duration (based on individual patterns
      of cell cycle progression) and to patients who received cycles of variable
      frequency (based on individual CD4(+) T lymphocyte responses to previous cycles).
      Twenty-two patients with HIV-1 infection and CD4(+) T lymphocyte counts > 200
      cells/mm(3) were randomized to one of three treatment groups for 32 weeks of
      study. Eight participants received four 5-day IL-2 cycles (controls) every 8
      weeks; 7 participants received four cycles of longer duration (mean 7.7-days);
      and 7 participants received an increased frequency of 5-day cycles (every 4.1
      weeks on average). All three groups experienced significant increases in mean
      CD4(+) T lymphocytes. However, there were no statistically significant
      differences in CD4(+) T lymphocyte increases between the group that received
      longer cycles (median increase 239 cells/mm(3), P = 0.78) or between the group
      that received more frequent cycles (median increase 511 cells/mm(3), P = 0.54)
      and the control group (median 284 cells/mm(3)). HIV-1 viral loads decreased
      during the study period in all three groups. Our inability to demonstrate a
      significant advantage of increased frequency or duration of IL-2 administration
      provides corroborating experimental evidence for the use of an IL-2 regimen
      consisting of 5-day cycles administered no more frequently than every 8 weeks in
      future clinical trials aimed at expanding the CD4(+) T lymphocyte pool.

PMID- 11286540
TI  - Chemokines have diverse abilities to form solid phase gradients.
AB  - Chemokines play critical roles in leukocyte recruitment into sites of
      inflammation such as rheumatoid arthritis (RA). While chemokines immobilized on
      endothelium (solid-phase), but not soluble chemokines, direct rolling leukocytes
      to firmly adhere to endothelium, soluble and solid-phase chemokine gradients may
      play important roles in leukocyte extravasation into the tissue. In this study,
      we have sought to determine (1) if chemokines can be immobilized on structures in
      the extravascular space, (2) the mechanisms by which chemokines may be
      immobilized, and (3) if different chemokines have similar potentials to form
      solid-phase gradients. While secreted alkaline phosphatase (SEAP)-tagged
      chemokines SLC (CCL21), TARC (CCL17), and RANTES (CCL5) bound to mast cells and
      the extracellular matrix (ECM) in RA synovium under physiologic salt conditions,
      MCP1 (CCL2), MIP1 alpha (CCL3), MIP1 beta (CCL4), and fractalkine (FKN, CX3CL1)
      fusion proteins did not detectably bind. Chemokine binding to ECM and mast cells
      in situ and to immobilized heparin was inhibited by high salt and
      glycosaminoglycans (GAGs) heparin, heparan sulfate, chondroitin sulfate, and
      dermatan sulfate, but not by dextran or hyaluronan, indicating that the
      chemokines bind to highly sulfated GAGs. Chemokine binding to synovial structures
      correlated strongly with avidity of chemokine binding to heparin (SLC > TARC >
      RANTES > MIP1 beta > MCP1 > MIP1 alpha > FKN). A RANTES mutant with decreased
      avidity for heparin was not able to bind to ECM or mast cells. Thus, these data
      indicate that chemokines can bind to ECM and mast cell granule constituents in
      situ via interactions with GAGs. Further, only a subset of chemokines were able
      to bind efficiently to structures in the extravascular space, indicating that
      chemokines may form different types of gradients based on their GAG binding
      ability and that chemotactic gradients in tissues may be quite complex.

PMID- 11286541
TI  - Decreased natural killer (NK) cell function in chronic NK cell lymphocytosis
      associated with decreased surface expression of CD11b.
AB  - Chronic natural killer cell lymphocytosis (CNKL) is characterized by greatly
      increased numbers of natural killer (NK) cells and patients with this disease may
      survive for long periods. This is in contrast to patients with leukemic
      proliferations of NK cells who can have a rapidly progressive clinical course. We
      identified a pediatric patient who was largely healthy who had CNKL and we sought
      to determine if the expanded CD16(+)CD3(-) population in this patient functions
      differently than classical NK cells. Cytotoxic activity against NK cell-sensitive
      K562 target cells was present, but lower than that in control donors when
      calculated as lytic units per CD16(+)CD3(-) cell. This cytolytic activity was
      inducible in patient samples by IL-2/IL-12 stimulation proportionately to that
      induced in samples from control donors. Intracellular perforin was also present
      and induced in patient CD16(+)CD3(-) cells similarly to controls. Other presumed
      NK cell activities, such as IL-2/IL-12 induced IFN-gamma expression and
      initiation of apoptosis evidenced by annexin V binding after CD16 crosslinking
      were present in patient samples. Patient CD16(+)CD3(-) cells, however, differed
      from classical NK cells, as the majority did not express CD56, CD57, CD8, or
      CD11b. Most convincingly, there was a 5 log decrease in CD11b expression in
      patient CD16(+)CD3(-) cells compared to control as determined by mean channel
      fluorescence. These observed differences may explain the relatively benign
      phenotype of this disorder.

PMID- 11286542
TI  - Incidence of GM-CSF antibodies in cancer patients receiving GM-CSF for
      immunostimulation.
AB  - We have assessed the immunogenicity profile of GM-CSF in patients with either
      colorectal carcinoma (CRC) at different stages of disease or with multiple
      myeloma who were given recombinant human GM-CSF (Escherichia coli-derived)
      combination therapy. Metastatic CRC patients received a colon carcinoma-reactive
      antibody and high doses of GM-CSF (425--500 microg/day for 10 days), while other
      CRC patients and those with myeloma received low doses of GM-CSF (75--80
      microg/day for 4 days) as an adjuvant along with appropriate tumor antigens. We
      found that 55% of the patients (11/20) given high doses of GM-CSF developed GM
      CSF-reactive antibodies in comparison with an incidence of only 16% (4/25) in
      patients given low doses of GM-CSF. None of the patients developed neutralizing
      antibodies and so the biological effects of GM-CSF were not compromised. A
      majority of patients (80%) (36/45) also developed antibodies to E. coli proteins
      that were present as trace contaminants in the GM-CSF product. Treatment with
      recombinant GM-CSF products, therefore, may induce antibodies against this
      cytokine depending on the regimen and the amounts used. In this study, multiple
      immunizations with low doses of GM-CSF was associated with a low incidence of GM
      CSF antibodies, which did not neutralize the effect of the cytokine. This
      therapeutic strategy was effective in inducing adjuvant-type effects and needs to
      be explored in further clinical trials with this cytokine.

PMID- 11286543
TI  - Expression and activation of a C-terminal truncated isoform of STAT5 (STAT5
      Delta) following interleukin 2 administration or AZT monotherapy in HIV-infected
      individuals.
AB  - Intermittent administration of recombinant interleukin-2 (rIL-2) to individuals
      infected with human immunodeficiency virus (HIV) has been shown to raise and
      maintain the absolute number of circulating CD4(+) T cells to normal or near
      normal levels. One of the signaling pathways triggered by IL-2 is the Janus
      kinase-signal transducer and activator of transcription (JAK-STAT). In
      particular, IL-2 activates the tyrosine kinases JAK1 and JAK3 and the
      transcription factors STAT3 and STAT5. We have previously observed that most
      HIV(+) individuals, unlike healthy seronegative controls, show a constitutive
      activation of STAT1 and a C-terminal truncated isoform of STAT5 (STAT5 Delta). In
      the present study, we have analyzed the protein level and activation state of
      STAT5 isoforms expressed in peripheral blood mononuclear cells of two HIV
      infected individuals who showed a good or a poor response to intermittent IL-2
      administration, respectively, and of a single individual before and after
      initiation of Zidovudine monotherapy. We provide evidence that both therapeutic
      interventions enhanced the expression and activation of the C-terminal truncated
      isoform of STAT5 (STAT5 Delta) in vivo.

PMID- 11286544
TI  - Vitamin D(3) and its synthetic analogs inhibit the spontaneous in vitro
      immunoglobulin production by SLE-derived PBMC.
AB  - The production of high-affinity pathogenic autoantibodies in systemic lupus
      erythematosus (SLE) may result from aberrant immune regulation. Since 1,25
      dihydroxy vitamin D(3) (1,25 D(3)) has immunoregulatory activity, we examined
      effects of 1,25 D(3) and its analogs HM, V, MC1288, and KH1060 on autoantibody
      production and proliferation of SLE PBMC. We found, in SLE, a higher percentage
      of T, B, and NK expressing vitamin D(3) receptors (VDRs) (P = 0.034, 0.006,
      0.012, respectively). Incubating SLE PBMC with 1,25 D(3) compounds significantly
      reduced proliferation, polyclonal and anti-dsDNA IgG production, and the
      percentages of CD3(+)/DR(+) T and B (CD19(+)) cells, while elevating NK (CD16(+))
      cells (P < 0.001). 1,25 D(3) analogs were more potent than the natural compound:
      KH1060 up-regulated CD14 expression by SLE monocytes (P < 0.001), inhibited
      polyclonal and anti-dsDNA IgG production by SLE-derived B lymphoblasts, and
      induced apoptosis of activated B lymphoblasts. These data suggest that 1,25 D(3)
      compounds can offer novel approaches to the clinical management of SLE.

PMID- 11286545
TI  - A case of X-linked agammaglobulinemia diagnosed in adulthood.
AB  - X-linked agammaglobulinemia (XLA), caused by mutations in Bruton's tyrosine
      kinase (BTK), typically presents in early childhood. We report here the case of a
      male diagnosed at age 23 years with hypogammaglobulinemia, originally classified
      as common variable immunodeficiency (CVID). On further analysis at age 40, flow
      cytometric analysis of lymphocytes showed only 0.1% B cells and Western blot
      analysis showed a deficiency of BTK protein in peripheral blood mononuclear
      cells, indicating the patient has XLA. BTK cDNA and genomic DNA analysis revealed
      a splice site mutation at the 3' end of intron 13. Multiple abnormally spliced
      mRNA species were identified, one of which was predicted to produce a protein
      with a 24-amino-acid insertion between the SH2 and kinase domains. In vitro
      kinase assay of this product showed weak kinase activity, perhaps resulting in
      milder than usual disease. XLA can present in adult males, and sporadic cases may
      be misdiagnosed as CVID.

PMID- 11286546
TI  - Comparing flow cytometry of sputum, bronchoalveolar lavage, and peripheral blood
      cells in healthy individuals.

PMID- 11286548
TI  - Phosphorylation causes subtle changes in solvent accessibility at the interdomain
      interface of methylesterase CheB.
AB  - The crystal structure of the unphosphorylated state of methylesterase CheB shows
      that the regulatory domain blocks access of substrate to the active site of the
      catalytic domain. Phosphorylation of CheB at Asp56 results in a catalytically
      active transiently phosphorylated enzyme with a lifetime of approximately two
      seconds. Solvent accessibility changes in this transiently phosphorylated state
      were probed by MALDI-TOF-detected amide hydrogen/deuterium exchange. No changes
      in solvent accessibility were seen in the regulatory domain upon phosphorylation
      of Asp56, but two regions in the catalytic domain (199-203 and 310-317) became
      more solvent accessible. These two regions flank the active site and contain
      domain-domain contact residues. Comparison with results from the isolated
      catalytic domain-containing C-terminal fragment of CheB (residues 147-349) showed
      that the increased solvent accessibility was less than would have occurred upon
      detachment of the regulatory domain. Thus, phosphorylation causes subtle changes
      in solvent accessibility at the interdomain interface of CheB.

PMID- 11286549
TI  - Effects of histone acetylation on the equilibrium accessibility of nucleosomal
      DNA target sites.
AB  - Posttranslational acetylation of the conserved core histone N-terminal tail
      domains is linked to gene activation, but the molecular mechanisms involved are
      not known. In an earlier study we showed that removing the tail domains
      altogether by trypsin proteolysis (which leaves nucleosomes nevertheless intact)
      leads to 1.5 to 14-fold increases in the dynamic equilibrium accessibility of
      nucleosomal DNA target sites. These observations suggested that, by modestly
      increasing the equilibrium accessibility of buried DNA target sites, histone
      acetylation could result in an increased occupancy by regulatory proteins,
      ultimately increasing the probability of transcription initiation. Here, we
      extend these observations to a more natural system involving intact but
      hyperacetylated nucleosomes. We find that histone hyperacetylation leads to 1.1
      to 1.8-fold increases in position-dependent equilibrium constants for exposure of
      nucleosomal DNA target sites, with an average increase of 1.4(+/-0.1)-fold. The
      mechanistic and biological implications of these results are discussed.

PMID- 11286550
TI  - Sequence dependence of translational positioning of core nucleosomes.
AB  - The basis for the choice of translational position of a histone octamer on DNA is
      poorly understood. To gain further insights into this question we have studied
      the translational and rotational settings of core particles assembled on a simple
      repeating 20 bp positioning sequence. We show that the translational positions of
      the core particles assembled on this sequence are invariant with respect to the
      DNA sequence and occur at 20 bp intervals. Certain modifications of the original
      sequence reduce the spacing of possible dyads to 10 bp. At least one of these
      alters both the translational and rotational settings. We conclude that the
      translational position of a core particle is specified by sequence determinants
      additional to those specifying rotational positioning. The rotational settings on
      either side of the dyads of core particles assembled on the wild-type and a
      mutant sequence differ by +2 bp, corresponding to an overall helical periodicity
      of approximately 10.15 bp. The average helical periodicity of the central two to
      four turns is 10.5-11 bp whilst that of the flanking DNA is closer to 10 bp. The
      DNA immediately flanking the dyad is also characterised by a more extensive
      susceptibility to cleavage by hydroxyl radical.

PMID- 11286551
TI  - Mapping arm-DNA-binding domain interactions in AraC.
AB  - AraC protein, the regulator of the l-arabinose operon in Escherichia coli has
      been postulated to function by a light switch mechanism. According to this
      mechanism, it should be possible to find mutations in the DNA-binding domain of
      AraC that result in weaker arm-DNA-binding domain interactions and which make the
      protein constitutive, that is, it no longer requires arabinose to activate
      transcription. We isolated such mutations by randomizing three contiguous leucine
      residues in the DNA-binding domain, and then by systematically scanning surface
      residues of the DNA-binding domain with alanine and glutamic acid. As a result, a
      total of 20 constitutive mutations were found at ten different positions. They
      form a contiguous trail on the DNA-distal face of the DNA-binding domain, and
      likely define the region where the N-terminal arm that extends from the N
      terminal dimerization domain contacts the C-terminal DNA-binding domain.

PMID- 11286552
TI  - The prion protein has DNA strand transfer properties similar to retroviral
      nucleocapsid protein.
AB  - The transmissible spongiform encephalopathies are fatal neurodegenerative
      diseases that are associated with the accumulation of a protease-resistant form
      of the cellular prion protein (PrP). Although PrP is highly conserved and widely
      expressed in vertebrates, its function remains a matter of speculation. Indeed
      PrP null mice develop normally and are healthy. Recent results show that PrP
      binds to nucleic acids in vitro and is found associated with retroviral
      particles. Furthermore, in mice the scrapie infectious process appears to be
      accelerated by MuLV replication. These observations prompted us to further
      investigate the interaction between PrP and nucleic acids, and compare it with
      that of the retroviral nucleocapsid protein (NC). As the major nucleic acid
      binding protein of the retroviral particle, NC protein is tightly associated with
      the genomic RNA in the virion nucleocapsid, where it chaperones proviral DNA
      synthesis by reverse transcriptase. Our results show that the human prion protein
      (huPrP) functionally resembles NCp7 of HIV-1. Both proteins form large
      nucleoprotein complexes upon binding to DNA. They accelerate the hybridization of
      complementary DNA strands and chaperone viral DNA synthesis during the minus and
      plus DNA strand transfers necessary to generate the long terminal repeats. The
      DNA-binding and strand transfer properties of huPrP appear to map to the N
      terminal fragment comprising residues 23 to 144, whereas the C-terminal domain is
      inactive. These findings suggest that PrP could be involved in nucleic acid
      metabolism in vivo.

PMID- 11286553
TI  - Two divalent metal ions in the active site of a new crystal form of human
      apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic
      mechanism.
AB  - The major human abasic endonuclease, Ape1, is an essential DNA repair enzyme that
      initiates the removal of apurinic/apyrimidinic sites from DNA, excises 3'
      replication-blocking moieties, and modulates the DNA binding activity of several
      transcriptional regulators. We have determined the X-ray structure of the full
      length human Ape1 enzyme in two new crystal forms, one at neutral and one at
      acidic pH. The new structures are generally similar to the previously determined
      structure of a truncated Ape1 protein, but differ in the conformation of several
      loop regions and in spans of residues with weak electron density. While only one
      active-site metal ion is present in the structure determined at low pH, the
      structure determined from a crystal grown at the pH optimum of Ape1 nuclease
      activity, pH 7.5, has two metal ions bound 5 A apart in the active site. Enzyme
      kinetic data indicate that at least two metal-binding sites are functionally
      important, since Ca(2+) exhibits complex stimulatory and inhibitory effects on
      the Mg(2+)-dependent catalysis of Ape1, even though Ca(2+) itself does not serve
      as a cofactor. In conjunction, the structural and kinetic data suggest that Ape1
      catalyzes hydrolysis of the DNA backbone through a two metal ion-mediated
      mechanism.

PMID- 11286554
TI  - Structural studies on the empty capsids of Physalis mottle virus.
AB  - The three-dimensional crystal structure of the empty capsid of Physalis mottle
      tymovirus has been determined to 3.2 A resolution. The empty capsids crystallized
      in the space group P1, leading to 60-fold non-crystallographic redundancy. The
      known structure of Physalis mottle virus was used as a phasing model to initiate
      the structure determination by real-space electron-density averaging. The main
      differences between the structures of the native and the empty capsids were in
      residues 10 to 28 of the A-subunit, residues 1 to 9 of the B-subunit and residues
      1 to 5 of the C-subunit, which are ordered only in the native virus particles. An
      analysis of the subunit disposition reveals that the virus has expanded radially
      outward by approximately 1.8 A in the empty particles. The A-subunits move in a
      direction that makes 10 degrees to the icosahedral 5-fold axes of symmetry. The B
      and C-subunits move along vectors making 12 degrees and 15 degrees to the quasi 6
      fold axes. The quaternary organization of the pentameric and hexameric capsomeres
      are not altered significantly. However, the pentamer-hexamer contacts are
      reduced. Therefore, encapsidation of RNA appears to cause a reduction in the
      particle radius concomittant with the ordering of the N-terminal arm in the three
      subunits. These structural changes in Physalis mottle virus appear to be larger
      than the corresponding changes observed in viruses for which both the empty and
      full particle structures have been determined.

PMID- 11286555
TI  - Sequence and crystal structure determination of a basic phospholipase A2 from
      common krait (Bungarus caeruleus) at 2.4 A resolution: identification and
      characterization of its pharmacological sites.
AB  - This is the first phospholipase A2 (PLA2) structure from the family of kraits.
      The protein was isolated from Bungarus caeruleus (common krait) and the primary
      sequence was determined using cDNA approach. Three-dimensional structure of this
      presynaptic neurotoxic PLA2 from group I has been determined by molecular
      replacement method using the model of PLA2 component of beta2-bungarotoxin
      (Bungarus multicinctus) and refined using CNS package to a final R-factor of 20.1
      % for all the data in resolution range 20.0-2.4 A. The final refined model
      comprises 897 protein atoms and 77 water molecules. The overall framework of
      krait phospholipase A2 with three long helices and two short antiparallel beta
      strands is extremely similar to those observed for other group I PLA2s. However,
      the critical parts of PLA2 folding are concerned with its various functional
      loops. The conformations of these loops determine the efficiency of enzyme action
      and presence/absence of various pharmacological functions. In the present
      structure calcium-binding loop is occupied by a sodium ion with a 7-fold co
      ordination. The conformation of loop 55-75 in krait PLA2 corresponds to a very
      high activity of the enzyme. A comparison of its sequence with multimeric PLA2s
      clearly shows the absence of critical residues such as Tyr3, Trp61 and Phe64,
      which are involved in the multimerization of PLA2 molecules. The protein shows
      anticoagulant and neurotoxic activities.

PMID- 11286556
TI  - Conformational properties of alpha-synuclein in its free and lipid-associated
      states.
AB  - alpha-Synuclein (alphaS) is a presynaptic terminal protein that is believed to
      play an important role in the pathogenesis of Parkinson's disease (PD). We have
      used NMR spectroscopy to characterize the conformational properties of alphaS in
      solution as a free monomer and when bound to lipid vesicles and lipid-mimetic
      detergent micelles. Free wild-type alphaS is largely unfolded in solution, but
      exhibits a region with a preference for helical conformations that may be
      important in the aggregation of alphaS into fibrils. The N-terminal region of
      alphaS binds to synthetic lipid vesicles and detergent micelles in vitro and
      adopts a highly helical conformation, consistent with predictions based on
      sequence analysis. The C-terminal part of the protein does not associate with
      either vesicles or micelles, remaining free and unfolded. These results suggest
      that one function of alphaS may be to tether as of yet unidentified partners to
      lipid surfaces via interactions with its C-terminal tail.

PMID- 11286557
TI  - Backbone dynamics of Escherichia coli thioesterase/protease I: evidence of a
      flexible active-site environment for a serine protease.
AB  - Escherichia coli thioesterase/protease I (TEP-I) is a member of a novel subclass
      of the lipolytic enzymes with a distinctive GDSLS motif. In addition to
      possessing thioesterase and protease activities, TEP-I also exhibits arylesterase
      activity. We have determined the (15)N nuclear magnetic spin relaxation rates,
      R(1) and R(2), and the steady state (1)H-(15)N heteronuclear Overhauser effect,
      measured at both 11.74 T and 14.09 T, of (u-(15)N) TEP-I. These data were
      analyzed using model-free formalism (with axially symmetric rotational diffusion
      anisotropy) to extract the backbone dynamics of TEP-I. The results reveal that
      the core structure of the central beta-sheet and the long alpha-helices are
      rigid, while the binding pocket appears to be rather flexible. The rigid core
      serves as a scaffold to anchor the essential loops, which form the binding
      pocket. The most flexible residues display large amplitude fast (ps/ns time
      scale) motion and lie on one stripe whose orientation is presumed to be the
      ligand-binding orientation. We also detected the presence of several residues
      displaying slow (microseconds/ms time-scale) conformational exchanging processes.
      These residues lie around the binding pocket and are oriented perpendicularly to
      the orientation of the flexible stripe. Two of the putative catalytic triads,
      Ser10 and His157, and their neighbors show motion on the microseconds/ms time
      scale, suggesting that their slow motion may have a role in catalysis, in
      addition to their possible roles in ligand binding. The presence of a flexible
      substrate-binding pocket may also facilitate binding to a wide range of
      substrates and confer the versatile functional property of this protein.

PMID- 11286558
TI  - Volume, expansivity and isothermal compressibility changes associated with
      temperature and pressure unfolding of Staphylococcal nuclease.
AB  - We have characterized the temperature- and pressure-induced unfolding of
      staphylococcal nuclease (Snase) using high precision densitometric measurements.
      The changes in the apparent specific volume, expansion coefficient and isothermal
      compressibility were determined by these measurements. To our knowledge, these
      are the first measurements of the volume and isothermal compressibility changes
      of a protein undergoing pressure-induced unfolding. In order to aid in
      interpreting the temperature and pressure dependence of the apparent specific
      volume of Snase, we have also carried out differential scanning calorimetry under
      the solution conditions which are used for the volumetric studies. We have seen
      that large compensating volume and compressibility effects accompany the
      temperature and pressure-induced protein unfolding. Measurements of the apparent
      specific volume and thermal expansion coefficient of Snase at ambient pressure
      indicate the formation of a pre-transitional, molten globule type of intermediate
      structure about 10 degrees C below the actual unfolding temperature of the
      protein. Compared to the folded state, the apparent specific volume of the
      unfolded protein is about 0.3-0.5 % smaller. In addition, we investigated the
      pressure dependence of the apparent specific volume of Snase at a number of
      different temperatures. At 45 degrees C we calculate a decrease in apparent
      specific volume due to pressure-induced unfolding of -3.3 10(-3) cm(3) g(-1) or 
      55 cm(3) mol(-1). The threefold increase in compressibility between 40 and 70 MPa
      reflects a transition to a partially unfolded state, which is consistent with our
      results obtained for the radius of gyration of the pressure-denatured state of
      Snase. At the lower temperature of 35 degrees C, a significant increase in
      compressibility around 30 MPa is indicative of the formation of a pressure
      induced molten globule-like intermediate. Changes in the apparent volume,
      expansion coefficient and isothermal compressibility are discussed in terms of
      instrinsic, hydrational and thermal contributions accompanying the unfolding
      transition.

PMID- 11286559
TI  - The importance of hinge sequence for loop function and catalytic activity in the
      reaction catalyzed by triosephosphate isomerase.
AB  - We have determined the sequence requirements for the N-terminal protein hinge of
      the active-site lid of triosephosphate isomerase. The codons for the hinge (PVW)
      were replaced with a genetic library of all possible 8000 amino acid
      combinations. The most active of these 8000 mutants were selected using in vivo
      complementation of a triosephosphate isomerase-deficient strain of Escherichia
      coli, DF502. Approximately 0.3 % of the mutants complement DF502 with an activity
      that is between 10 and 70 % of wild-type activity. They all contain Pro at the
      first position. Furthermore, the sequences of these hinge mutants reveal that
      hydrophobic packing is very important for efficient formation of the enediol
      intermediate. However, the reduced catalytic activities observed are not due to
      increased rates of loop opening. To explore the relationship between the N
      terminal and C-terminal hinges, three semi-active mutants from the N-terminal
      hinge selection experiment (PLH, PHS and PTF), and six active C-terminal hinge
      mutants from previous work (NSS, LWA, YSL, KTK, NPN, KVA) were combined to form
      18 "double-hinge" mutants. The activities of these mutants suggest that the N
      terminal and C-terminal hinge structures affect one another. It appears that
      specific side-chain interactions are important for forming a catalytically active
      enzyme, but not for preventing release of the unstable enediol intermediate from
      the active site of the enzyme. The independence of intermediate release on amino
      acid sequence is consistent with the absence of a "universal" hinge sequence in
      structurally related enzymes.

PMID- 11286560
TI  - Evolution of function in protein superfamilies, from a structural perspective.
AB  - The recent growth in protein databases has revealed the functional diversity of
      many protein superfamilies. We have assessed the functional variation of
      homologous enzyme superfamilies containing two or more enzymes, as defined by the
      CATH protein structure classification, by way of the Enzyme Commission (EC)
      scheme. Combining sequence and structure information to identify relatives, the
      majority of superfamilies display variation in enzyme function, with 25 % of
      superfamilies in the PDB having members of different enzyme types. We determined
      the extent of functional similarity at different levels of sequence identity for
      486,000 homologous pairs (enzyme/enzyme and enzyme/non-enzyme), with structural
      and sequence relatives included. For single and multi-domain proteins, variation
      in EC number is rare above 40 % sequence identity, and above 30 %, the first
      three digits may be predicted with an accuracy of at least 90 %. For more
      distantly related proteins sharing less than 30 % sequence identity, functional
      variation is significant, and below this threshold, structural data are essential
      for understanding the molecular basis of observed functional differences. To
      explore the mechanisms for generating functional diversity during evolution, we
      have studied in detail 31 diverse structural enzyme superfamilies for which
      structural data are available. A large number of variations and peculiarities are
      observed, at the atomic level through to gross structural rearrangements. Almost
      all superfamilies exhibit functional diversity generated by local sequence
      variation and domain shuffling. Commonly, substrate specificity is diverse across
      a superfamily, whilst the reaction chemistry is maintained. In many
      superfamilies, the position of catalytic residues may vary despite playing
      equivalent functional roles in related proteins. The implications of functional
      diversity within supefamilies for the structural genomics projects are discussed.
      More detailed information on these superfamilies is available at
      http://www.biochem.ucl.ac.uk/bsm/FAM-EC/.

PMID- 11286561
TI  - The active site of the junction-resolving enzyme T7 endonuclease I.
AB  - Endonuclease I is a junction-resolving enzyme encoded by bacteriophage T7, that
      selectively binds and cleaves four-way DNA junctions. We have recently solved the
      structure of this dimeric enzyme at atomic resolution, and identified the
      probable catalytic residues. The putative active site comprises the side-chains
      of three acidic amino acids (Glu20, Asp55 and Glu65) together with a lysine
      residue (Lys67), and shares strong similarities with a number of type II
      restriction enzymes. However, it differs from a typical restriction enzyme as the
      proposed catalytic residues in both active sites are contributed by both
      polypeptides of the dimer. Mutagenesis experiments confirm the importance of all
      the proposed active site residues. We have carried out in vitro complementation
      experiments using heterodimers formed from mutants in different active site
      residues, showing that Glu20 is located on a different monomer from the remaining
      amino acid residues comprising the active site. These experiments confirm that
      the helix-exchanged architecture of the enzyme creates a mixed active site in
      solution. Such a composite active site structure should result in unilateral
      cleavage by the complemented heterodimer; this has been confirmed by the use of a
      cruciform substrate. Based upon analogy with closely similar restriction enzyme
      active sites and our mutagenesis experiments, we propose a two-metal ion
      mechanism for the hydrolytic cleavage of DNA junctions.

PMID- 11286562
TI  - Developmental expression of vascular endothelial growth factor (VEGF) receptors
      and VEGF binding in ovine placenta and fetal membranes.
AB  - The receptor tyrosine kinases, kinase-insert domain-containing receptor (KDR) and
      fms-like tyrosine kinase (Flt-1), and their ligand vascular endothelial growth
      factor (VEGF) are essential for the development and maintenance of placental
      vascular function during pregnancy. To further understand the role of VEGF in
      mediating angiogenesis and vascular permeability during development, the cellular
      localization of KDR and Flt-1 mRNA and protein, and the distribution of(125)I
      VEGF binding sites in placenta, chorion and amnion of ovine fetuses were examined
      at three different gestational ages. In placentae at 62, 103 and 142 days, the
      predominant site of KDR mRNA and protein, and VEGF binding was the maternal
      vascular endothelium. In addition, a specific, although weak, signal for KDR mRNA
      was found in the maternal epithelium. At 103 and 142 days but not 62 days
      gestation, KDR mRNA and protein as well as VEGF binding sites were abundantly
      present in the endothelium of villous blood vessels. In the fetal membranes at
      62, 103 and 142 days gestation, KDR mRNA and protein were expressed in the
      amniotic epithelium and intramembranous blood vessel endothelium, where binding
      of(125)I-VEGF was strong. There was no KDR mRNA or VEGF binding in the chorionic
      cytotrophoblast. Flt-1 expression was not detectable in placentae or fetal
      membranes at the three ages studied. In summary, the results demonstrated that
      VEGF receptors are present in the maternal and fetal vasculatures of the ovine
      placenta. This expression is consistent with a capillary growth-promoting
      function of KDR and its ligand VEGF. Further, the presence of KDR and VEGF
      binding sites in ovine fetal membranes suggests a role for VEGF in promoting
      intramembranous vascularity and permeability throughout gestation.

PMID- 11286563
TI  - Developmental regulation of morphological differentiation of placental villous
      trophoblast in the baboon.
AB  - The present study determined whether morphological differentiation of placental
      villous cytotrophoblasts into syncytiotrophoblast during primate pregnancy was
      developmentally regulated and whether oestrogen has a role in this process.
      Placental volumetric composition of the cytotrophoblast and syncytiotrophoblast
      was determined by the test-point counting method on days 45-54, 60, 100, and 170
      of gestation (term=184 days) in untreated baboons, on day 60 after placental
      oestrogen production was prematurely elevated by administration of aromatizable
      androstenedione or oestradiol, and on day 170 after oestrogen production was
      suppressed by administration of aromatase inhibitor CGS 20267. Cytotrophoblast
      and syncytiotrophoblast volumes and oestrogen levels increased (P< 0.01) with
      advancing gestation. Due to the rise in syncytiotrophoblast volume (12-fold)
      exceeded that of the cytotrophoblast (threefold), the mean (sem) ratio of
      syncytiotrophoblast and cytotrophoblast volumes increased (P< 0.001) from 3.4
      (0.5) ml on day 60 to 12.1 (2.8) ml on day 170. Androstenedione administration
      elevated serum oestradiol levels threefold (P< 0.01) and increased the ratio of
      syncytiotrophoblast: cytotrophoblast volumes on day 60 by 50 per cent (P< 0.03)
      to that normally observed on day 100. However, the ratio of trophoblast volumes
      was unaltered in oestradiol-treated and CGS 20267-treated baboons. It is
      concluded that there is a developmental increase in morphological differentiation
      of the placental villous trophoblast during primate pregnancy and that
      androstenedione potentially via its conversion to oestrogen has a role in this
      process.

PMID- 11286564
TI  - Structure of anchoring villi and the trophoblastic shell in the human, baboon and
      macaque placenta.
AB  - Anchoring villi of first trimester placentae of the macaque, baboon and human
      were examined by light and electron microscopy. The anchoring villi of the baboon
      and macaque are similar in having more elongated cell columns than those of the
      human and in having more extracellular matrix between cytotrophoblast cells.
      These species also have a thicker and more uniform trophoblastic shell. The
      generative region of cytotrophoblast cells adjacent to the villous mesenchyme is
      similar in all three species, with the aspect of the core abutting this area
      being lined by a thickened basal lamina. Similarly, migratory cytotrophoblast
      cells form extracellular matrix in all three species, but matrix-rich regions of
      the anchoring villi and shell are more extensive in the non-human primates. The
      extracellular matrix and especially the material resembling fibrillin may serve
      to strengthen the villi, particularly the elongated villi of the non-human
      primate, and also may prevent maternal cells migrating into the trophoblastic
      shell. The baboon and macaque cytotrophoblast cells that form this matrix tend to
      be linked by gap and desmosomal junctions and are in contiguous arrays, whereas
      those in the human that are blocked from reaching normal decidua form abundant
      extracellular matrix but have no gap junctions. Whether the lack of extensive
      invasion of the endometrium by baboon and macaque cytotrophoblast cells is
      related to the increased amount of extracellular matrix, their greater distance
      from the mesenchymal core, or their intercellular linkages is not known. The
      investigation of isolated villi from the macaque or baboon, as has been
      extensively carried out in the human, might help to determine whether the
      cytotrophoblast cells are intrinsically different or are responding to different
      environmental cues.

PMID- 11286565
TI  - Placental superoxide is increased in pre-eclampsia.
AB  - One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states
      that the placenta secretes one or more cytotoxic factors resulting in maternal
      endothelial dysfunction. Among the candidate factors are the products of
      increased oxidative stress. Although there is circumstantial evidence of such an
      increase, direct evidence is still lacking. Electron paramagnetic spin trap
      resonance (EPR), the most direct method to detect free radicals in tissues, was
      used to measure superoxide levels in placentae from normal pregnancies (n=13) and
      pregnancies complicated by PE (n=10). The superoxide level was significantly
      increased in the placental tissue of pre-eclamptic women. Moreover, upon
      inhibition of Cu-Zn superoxide dismutase (SOD) activity the relative increase of
      the superoxide levels was significantly smaller in the placentae from the PE
      patients, implying decreased basal Cu-Zn SOD activity. These findings lend direct
      support to the hypothesis that oxidative stress in placental tissue is increased
      in PE.

PMID- 11286566
TI  - Severely reduced presence of tissue macrophages in the basal plate of pre
      eclamptic placentae.
AB  - Pre-eclampsia is a disorder of unknown aetiology peculiar to human pregnancy. A
      well-described pathological feature being shallow trophoblast invasion into the
      spiral arteries during placenta development. Epidemiological studies have
      revealed an increased risk in pregnancies of primipaternity, and an association
      with the maternal-fetal HLA-DR relationship, both suggesting the involvement of
      an immunological component. We were therefore interested in the distribution of
      HLA-DR expressing myeloid cells in the decidua of healthy and pre-eclamptic
      placentae. We have studied the monocytes in maternal and fetal peripheral blood
      as well as in the placenta and identified the cluster of differentiation (CD)
      14(+)myeloid cells in the basal plate as mannose receptor (ManR) positive tissue
      macrophages. In a comparison between peripheral blood monocytes from healthy
      pregnant and pre-eclamptic women we found no significant difference in the
      subpopulation size of CD14(+)/CD16(+)monocytes. The number and location of
      macrophages in the placental villi was similar. However, while the basal plate of
      the normal decidua contained numerous CD14(+), HLA-DR(bright), ManR(+)tissue
      macrophages, this compartment was virtually void of these phagocytic cells in the
      pre-eclamptic placenta. This novel finding suggests that in pre-eclampsia not
      only the migration of endovascular cytotrophoblasts is disturbed, but that also
      maternal macrophage migration is affected.

PMID- 11286567
TI  - Differential expression of lactate dehydrogenase isozymes (LDH) in human placenta
      with high expression of LDH-A(4) isozyme in the endothelial cells of pre
      eclampsia villi.
AB  - To evaluate the role of LDH isozymes in the human placenta during the third
      trimester, placentae were obtained from patients with normal pregnancy and pre
      eclampsia. LDH-A(4)isozyme was immunolocalized primarily in the fetal endothelial
      cells while LDH-B(4)isozyme was predominantly present in syncytiotrophoblasts.
      This distinct cellular expression pattern of LDH isozymes was confirmed in HUVE
      and JEG cells. In addition to demonstrating the presence of five LDH isozymes in
      the placenta, zymograms showed that there was predominant activity of LDH
      A(4)isozyme in HUVE cells and high activity of LDH-B(4)in JEG cells. Quantitative
      studies of LDH by agarose gel electrophoresis and Northern analysis in patients
      concluded that LDH-A(4)isozyme was increased in pre-eclampsia. The LDH
      A(4)isozyme activity increased (P< 0.01) approx 1.6-fold in pre-eclampsia but
      there was no difference in the LDH-B(4)isozyme activity between placentae from
      normal compared to pre-eclampsia pregnancy. The level of LDH-A mRNA was increased
      (P< 0.05) approx twofold in pre-eclampsia. We conclude that the LDH-A gene in the
      endothelial cells of the placenta within the fetal microvasculature is increased
      in pre-eclampsia, probably as a result of hypoxia. LDH-A(4)isozyme activity and
      gene expression in placental endothelial cells, therefore, is a marker for the
      endothelial pathology seen in pre-eclampsia.

PMID- 11286568
TI  - Twin pregnancy consisting of 46, XY heterozygous complete mole coexisting with a
      live fetus.
AB  - Complete hydatidiform mole and coexistent fetus (CMCF) is a rare occurrence and
      is associated with an increased risk of persistent gestational trophoblastic
      diseases. The aim of this study was to reveal a potential risk factor and to
      determine optimum management of CMCF cases. Molar tissues are cytogenetically
      divided into two types, homozygous and heterozygous. The molar tissue of our case
      showed a 46, XY heterozygous complete mole. Genomic DNA was analyzed by the
      polymerase chain reaction using sets of unlabelled forward and Cy-5-labelled
      reverse primers for DNA marker loci. The patient developed persistent
      trophoblastic disease (PTD) with lung metastasis. Since 1980 there have been 13
      reports (including our case) that cytogenetically revealed CMCF and clarified the
      clinical outcome. Nine of the 16 CMCF cases before 21 weeks of gestation and
      seven of the 12 CMCF cases after 22 weeks of gestation developed PTD. The
      incidence of PTD from CMCF was not related to the gestational age at termination
      or delivery. There were 10 case reports that analyzed the zygosity of a mole,
      heterozygous or homozygous. Two of six homozygous and three of four heterozygous
      moles in CMCF cases developed PTD. A heterozygous mole is thought to be a high
      risk factor for the incidence of PTD. Cytogenetic study is clinically useful for
      the optimum management of CMCF cases.

PMID- 11286569
TI  - Inwardly rectifying K(+) current and differentiation of human placental
      cytotrophoblast cells in culture.
AB  - Ion transport is important for driving nutrient transport across the
      syncytiotrophoblast and yet is poorly understood. We have examined K(+)currents
      under basal conditions in cultured cytotrophoblast cells, at various stages of
      differentiation, using the whole cell patch clamp technique. Cytotrophoblast
      cells were isolated from human term placenta and maintained in culture for up to
      3 days. Cells were studied at four stages of progressive morphological
      differentiation: (i) mononuclear cells, (ii) mononuclear cells in aggregates,
      (iii) small multinucleate cells and (iv) large multinucleate syncytiotrophoblast
      like cells. In the conditions of whole cell recording the only K(+) selective
      current identified in all cell types was a strong inwardly rectifying current
      which was sensitive to Ba(2+) and Cs(+). This current was unaffected by
      intracellular ATP whereas intracellular GTPgammas caused either run down of the
      current or activated a linear current. The characteristics of the current
      described are consistent with those of the inwardly rectifying K(+) channel
      Kir2.1. The inwardly rectifying K(+) current was observed in three out of 19 (16
      per cent ) mononuclear cells, seven out of 21 (33 per cent ) mononuclear
      aggregates, eight out of 21 (38 per cent ) small multinucleate cells and 16 out
      of 19 (84 per cent ) large multinucleate cells. This inwardly rectifying K(+)
      current is likely to have an important role in determining net K(+) diffusion
      across the syncytiotrophoblast cell membrane, perhaps increasing in importance as
      the cells terminally differentiate.

PMID- 11286570
TI  - Effects of nitrovasodilators on the human fetal-placental circulation in vitro.
AB  - This study examines the vasorelaxation of isolated human placental chorionic
      plate arteries and the perfused fetal-placental vasculature, in vitro, to a
      variety of nitrovasodilator compounds including glyceryl trinitrate (GTN) sodium
      nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-N
      glutathione (SNG) and NaNO(2). The effects of these compounds were also examined
      under conditions of high (>450 mmHg) and low oxygen (<50 mmHg) tension. In a
      separate series of experiments the effects of GTN and NaNO(2)were further
      investigated with addition of the antioxidants cysteine (100 microm), glutathione
      (100 microm) or superoxide dismutase (SOD) (30 I.U./ml). The order of
      nitrovasodilator potency, when added directly to isolated fetal vessels was
      GTN=SNP>SNAP=SNG>NaNO(2). The order under low oxygen tension was similar,
      GTN=SNP>SNG= SNAP>or=NaNO(2). SNG ( approximately fourfold) and NaNO(2)(
      approximately 50-fold) were significantly more potent under low oxygen
      conditions. Cysteine, glutathione and SOD were without effect on GTN induced
      vasodilatation. However, all three agents significantly enhanced (six- to
      ninefold) the effects of NaNO(2)under similar conditions. When infused directly
      into the fetal-placental circulation during in vitro perfusion experiments the
      order of potency was GTN>SNP>or=SNG>or=SNAP>or=NaNO(2). When the
      nitrovasodilators were infused indirectly via the maternal intervillous space the
      order of potency was GTN>or=SNP>or=NaNO(2)>or=SNAP=SNG. Our observations suggest
      that there are important differences in the action of different classes of
      nitrovasodilator compounds on the fetal-placental circulation. The changes
      observed with SNG and NaNO(2)may be influenced by levels of tissue oxygenation.

PMID- 11286571
TI  - Leptin secretion to both the maternal and fetal circulation in the ex vivo
      perfused human term placenta.
AB  - The contribution of placental leptin, if any, to both the fetal and maternal
      circulation and its role in pregnancy remains to be determined. In an experiment
      to investigate this, 27 placentae from term pregnancies were perfused ex vivo
      (gestational age=39.5 s.d. 1.2; range=38-42 weeks: fetal weight=3285 s.d. 482;
      range=2480-4420; birthweight centile range=4th to the 98th) at both the maternal
      and fetal interface. Placental leptin was exported into both the maternal and
      fetal circulations. The log leptin production by the maternal side of the
      placenta was significantly greater (P=0.001) than that for the fetal side (5.193
      s.d.1.049 versus 4.387 s.d. 0.768 ng/placenta/min). There was no significant
      relationship between maternal and fetal log leptin production and maternal body
      mass index, birthweight, birthweight centile, ponderal index or gestational age
      or with cord blood pO(2), pCO(2) and pH. There was however, a significant
      increase in the maternal log leptin production with increasing fetal to placental
      weight ratio (P=0.017; r(2)=20.7 per cent) but no corresponding relationship for
      fetal leptin production. It is proposed that such a mechanism would allow the
      placenta to modulate fat supply to the fetus in response to the fetal demand
      relative to placental supply.

PMID- 11286572
TI  - Thyroid hormone receptor expression in rat placenta.
AB  - The expression of c- erbAalpha and -beta encoded thyroid hormone receptors (TR)
      was investigated in rat placenta between 16 and 21 days of gestation (dg), and in
      fetal liver and brain at 16 dg, using semi-quantitative RT-PCR and nuclear 3,5,3'
      triiodothyronine (T(3)) binding. TRalpha1, TRbeta1, c- erbAalpha 2 and c-
      erbAalpha 3 mRNA abundance was unchanged in placenta between 16 and 21 dg, as was
      the dissociation constant (K(d)) of T(3) binding. The maximal T(3) binding
      capacity (B(max)) in placenta doubled over this period, suggesting placental TR
      binding activity is post-transcriptionally regulated. Transcript abundance in
      tissues at 16 dg can be summarized: TRalpha1, placenta=fetal liver<fetal brain;
      TRbeta1, placenta=fetal liver>fetal brain; c- erbAalpha 2 and alpha3,
      placenta=fetal liver<fetal brain; TRbeta2; none detected. T(3)binding in fetal
      liver and brain exhibited equivalent K(d) and B(max), the K(d) being less than 50
      per cent of that in placenta, though B(max) was unchanged. The higher K(d)in
      placenta may reflect tissue-specific patterns of TR modification. In conclusion,
      rat placenta expresses significant levels of c- erbAalpha and -beta transcripts
      and protein, providing a possible mechanism of action for T(3) of maternal and
      fetal origin in this tissue.

PMID- 11286573
TI  - Study on risk factors for transplacental viral infections; effect of bacterial
      factors and double viral infections on virus replication in placenta and amniotic
      membranes.
AB  - Among risk factors for vertical transmission of HIV there are listed concomitant
      viral and bacterial infections. Therefore the influence on the viruses
      replication in human placenta and amniotic membrane cultures of double viral
      infection with two unrelated viruses - encephalomyocarditis (EMCV) and vesicular
      stomatitis virus (VSV) - was studied and compared with the replication of the
      viruses in single virus infection (EMCV or VSV) in the same organ cultures.
      Additionally effect of bacterial factors - lipopolysaccharide (LPS) Escherichia
      coli and sonicated Treponema pallidum antigens (Tpa) - on VSV replication in the
      same culture system was studied and compared with VSV replication in untreated
      explants. Two effects were observed in double-virus infected cultures and also in
      bacterial factors treated cultures: inhibition and stimulation of virus
      replication. The kind of effect in the both cases was dependent on the presence
      or absence of innate antiviral immunity. In virus-sensitive organs double
      infected or treated with LPS or Tpa, inhibition of virus titer (2-5 log
      TCID(50)/ml) was observed. In the organs expressing the innate immunity,
      stimulation (1-4 log TCID(50)/ml) of virus replication was noticed. Contribution
      of endogenous TNFalpha in both reactions (stimulation and inhibition) was
      confirmed using antibodies against the TNF.

PMID- 11286575
TI  - Decidual stromal cell-lymphocyte interactions in pregnancy.

PMID- 11286574
TI  - Presence of CD30(+) and CD30L(+) cells in human placenta and soluble CD30 levels
      in cord blood are independent of maternal atopy.
AB  - The intrauterine environment is characterized by a Th2 dominance during
      pregnancy, a milieu that also promotes atopic allergy. The aim of this study was
      to compare the presence of CD30, a molecule associated with Th2 related disorders
      such as atopic allergy, and its ligand (CD30L) in placenta in order to
      investigate if the placenta environment differs between atopic and non-atopic
      women. Serum concentrations of soluble CD30 (sCD30) from the mothers and their
      newborns were also elucidated. There were no differences in the
      immunohistochemical expression of CD30 and CD30L in placenta from atopic (n=28)
      compared with non-atopic (n=37) women. CD30 was expressed on the decidual stromal
      cells alone, while CD30L, previously not described in placenta, was detected on
      macrophage-like HLA-DR(+) cells throughout the mesenchymal chorionic villi. Serum
      sCD30 in atopic mothers was significantly elevated compared with serum sCD30 in
      non-atopic mothers (P< 0.05), while sCD30 levels in cord blood were similar in
      both groups independently of maternal atopic heredity. We suggest that sCD30 in
      cord blood and CD30 expression by decidual cells may reflect the Th2 environment
      surrounding the fetus, and both CD30 and CD30L could have immune regulatory
      functions in placenta.

PMID- 11286576
TI  - Current concepts in imaging of tendinopathy.
AB  - With the rising popularity of recreational sports, radiologists are being asked
      to image tendons with increasing frequency. Recognition of the critical link
      tendons provide between muscle and bone has also led to a better understanding of
      the processes leading to tendon damage. While plain radiography and CT have only
      a limited role to play in the diagnosis of tendon abnormality, the improvements
      in ultrasound and MRI technology mean that tendons can now be demonstrated in
      exquisite detail and previously undetectable abnormalities are readily
      demonstrated. This article reviews the structure and pathological processes
      affecting tendons and discusses the role of imaging in their assessment with an
      emphasis on ultrasound and MRI.

PMID- 11286577
TI  - The role of CT in the management of adult urinary tract trauma.
AB  - Computed tomography (CT) is now the investigation of choice for evaluating
      haematuria following major abdominal trauma. This pictorial review provides a
      logical framework for understanding the classification and features of urinary
      tract injuries, defines the indications and outlines the techniques for CT
      imaging in upper and lower urinary tract trauma. The use of other competing
      imaging modalities is also discussed.

PMID- 11286578
TI  - Differentiation of mammographically suspicious lesions: evaluation of breast
      ultrasound, MRI mammography and electrical impedance scanning as adjunctive
      technologies in breast cancer detection.
AB  - AIM: Various modalities are used as an adjunct to mammography for differentiation
      of potentially suspicious breast lesions. Electrical impedance scanning (EIS) is
      a new technique based upon the principle that cancer cells exhibit altered local
      dielectric properties and thus show measurably higher conductivity values. The
      accuracy of differentiation of benign and malignant breast lesions was evaluated
      to determine whether EIS duplicates or supplements the results obtainable from
      ultrasound (US) or magnetic resonance imaging (MRI). MATERIALS AND METHODS: One
      hundred mammographically suspicious lesions were examined using US, MRI and EIS.
      Definitive histology was acquired through either lesion biopsy or surgical
      excision. RESULTS: Fifty of 62 malignant lesions were correctly identified using
      EIS (81% overall sensitivity), 24/38 benign lesions were correctly identified as
      benign (63% specificity). Negative predictive value and positive predictive value
      of 67 and 78% were observed, respectively. kappa-factor evaluation revealed a
      value of 0.82 between MRI and EIS and 0.62 between US and EIS. CONCLUSIONS: EIS
      may be a valuable adjunct for differentiation of suspicious mammographic lesions.
      Based upon the calculated kappa-factor, EIS results supplement US examinations.
      Artifacts (superficial skin lesions, poor contact, air bubbles) currently result
      in the high false-positive rate of EIS.

PMID- 11286579
TI  - Power Doppler sonography of metastatic nodes from papillary carcinoma of the
      thyroid.
AB  - AIMS: Metastatic nodes on power Doppler sonography tend to demonstrate high
      intranodal resistance and abnormal distribution of vascularity within a node.
      However, in our experience metastatic nodes from papillary carcinoma of the
      thyroid frequently demonstrate low intranodal resistance and some do not
      demonstrate the presence of any abnormal vascularity within. We were therefore
      interested to document these features. MATERIALS AND METHODS: The grey scale and
      power Doppler sonograms of 21 metastatic nodes from papillary carcinoma of the
      thyroid were evaluated. The intranodal distribution of vessels and the intranodal
      vascular resistance of vessels was assessed and compared with the reported
      features of metastatic nodes from other head and neck primaries. RESULTS: A
      majority (17/20, 85%) of metastatic nodes from papillary carcinoma of the thyroid
      had a maximum resistance index (RI) and pulsatility index (PI) < 0.8 and 1.6,
      respectively. A majority of the nodes (16/21, 76%) demonstrated abnormal capsular
      vascularity within the nodes. CONCLUSION: Metastatic nodes from papillary
      carcinoma on power Doppler sonography frequently have low RI and PI and 24%
      demonstrate just prominent hilar vascularity similar to reactive nodes.

PMID- 11286580
TI  - Spinal ultrasound in cloacal exstrophy.
AB  - AIM: To assess the diagnostic value of spinal ultrasound in cloacal exstrophy, a
      caudal malformation which is associated with spinal dysraphism, and to assess the
      prevalence of spinal dysraphism in cloacal exstrophy. MATERIALS AND METHODS: Ten
      infants under 1 year old with cloacal exstrophy underwent spinal ultrasound at
      presentation. Three patients also had a magnetic resonance imaging (MRI)
      examination. Ultrasound and MRI images were reviewed and correlated. RESULTS:
      Nine of 10 patients had no external signs of spinal dysraphism. One patient had a
      clinically apparent myelomeningocele. Five of 10 patients (50%) had spinal
      dysraphism on ultrasound: there were two patients with a low cord, two with
      tethered cords and a lipoma, and one patient with tethering and a
      myelomeningocele. Thus, in four of these five patients spinal dysraphism was
      occult. In a small number of patients (n = 3) MRI was also performed-in these
      cases the MRI and ultrasound appearances correlated, however MRI was not
      performed in those patients in whom spinal ultrasound was normal. CONCLUSION: In
      three cases where spinal ultrasound detected occult dysraphism and MRI was
      performed, spinal ultrasound and MRI correlated. Advantages of spinal ultrasound
      include ease of examination, production of high quality multi-planar images and
      the facility for portable imaging at the bedside. Spinal ultrasound should be the
      first investigation in all babies with cloacal exstrophy to diagnose occult and
      non-occult spinal dysraphism.

PMID- 11286582
TI  - Multi-slice technology in computed tomography.
AB  - Multi-slice systems represent a considerable advance in CT and will assure the
      future of the technique for many years to come. This article describes this new
      technology, indicating its provenance and its position in the evolution of CT.
      While it does not seek to be a physics and engineering text, enough detail of
      these are given to allow an informed discussion of the many advantages and a few
      potential problems associated with the technology. A discussion of a number of
      applications and a brief consideration of contrast enhancement regimens and the
      possible need for their modification are presented.

PMID- 11286581
TI  - Imaging of primary non-Hodgkin's lymphoma of the liver.
AB  - AIM: To describe the radiological findings in primary liver lymphoma, which is a
      rare entity, presenting usually as a localized liver mass. MATERIALS AND METHODS:
      We reviewed retrospectively the imaging findings at presentation, of patients in
      whom a diagnosis of primary liver lymphoma was finally made histologically. The
      study period covered a 10-year period between January 1990 and December 1999.
      There were seven patients, all men, with a mean age of 49.6 years. Each patient
      presented with hepatobiliary disease without peripheral adenopathy. Imaging prior
      to diagnosis included ultrasonography (seven patients), computed tomography
      (seven patients) and magnetic resonance imaging (MRI) (two patients). Appearances
      during and after aggressive chemotherapy were reviewed. RESULTS: Imaging
      appearances were of either single or multiple liver lesions simulating liver
      metastases. On ultrasound all foci of primary hepatic lymphoma (PHL) were
      hypoechoic relative to normal liver. Computed tomography (CT) showed
      hypoattenuating lesions in all cases, and two cases showed rim enhancement
      following contrast administration. The MRI appearances were variable, and no
      pathognomonic feature of PHL was identified, so that histology was required in
      all patients to establish the diagnosis. CONCLUSIONS: This paper demonstrates the
      spectrum of findings encountered on various imaging modalities in PHL. We
      conclude that although PHL is a rare condition, it should always be considered in
      the differential diagnosis of liver metastases when no primary tumour is
      apparent.

PMID- 11286583
TI  - Documentation of in-training assessment for radiology trainees.
AB  - AIM: To determine if the assessment of radiology trainees can be improved by
      modifying the in-training assessment form issued by the Royal College of
      Radiologists (RCR). MATERIALS AND METHODS: A qualitative study comparing the RCR
      assessment form with other alternative forms in use in the U.K. Individual semi
      structured interviews were conducted with trainees (21) and trainers (18) in
      Sheffield to collect their views on the RCR form and an alternative form
      introduced on the North Trent Training Scheme. A postal questionnaire was sent to
      Heads of Training (24) to find out what assessment forms were in use at other
      centres and collect their views on the different forms. RESULTS: Trainees and
      trainers in Sheffield were virtually unanimous in their support of the new North
      Trent assessment form. The main advantages perceived were the encouragement of
      appraisal, setting of objectives and feedback from the trainees. Six other
      radiology training centres were using alternative assessment forms and all
      believed their forms had advantages over the RCR in-training assessment form.
      CONCLUSION: The results of this study suggest that the assessment process for
      radiology trainees can be improved by modifications to the RCR in-training
      assessment form and allows various recommendations to be made.

PMID- 11286584
TI  - Magnetic resonance imaging of suspected scaphoid fractures using a low field
      dedicated extremity MR system.
AB  - AIM: To determine whether magnetic resonance imaging (MRI) using a dedicated
      extremity system could be utilized for the routine assessment of patients with a
      clinically suspected scaphoid fracture, and to determine the most cost-effective
      timing of MRI for these patients. MATERIALS AND METHODS: MRI of the wrist using a
      0.2T extremity MR system was performed in two groups of patients. Fifty-six
      patients were examined within 4 days of injury and 53 with persistent symptoms at
      10 days to 6 weeks following injury. A scaphoid series of radiographs was
      negative in both groups. RESULTS: The early MR group had seven scaphoid, six
      radial and four other fractures. Management was altered in 89%. The late MR group
      had 14 scaphoid, nine radial and three other fractures. Management was altered in
      69%. A cost model showed that overall costs are less with early rather than late
      scanning. CONCLUSION: MRI of the wrist when scaphoid fracture is suspected can be
      undertaken in all patients with negative radiographs and could be performed in
      most departments with an MRI machine. There are significant patient benefits and
      overall costs would change little from conventional practice.

PMID- 11286585
TI  - Cardiopulmonary resuscitation and contrast media reactions in a radiology
      department.
AB  - AIM: To assess current knowledge and training in the management of contrast media
      reactions and cardiopulmonary resuscitation within a radiology department.
      MATERIALS AND METHODS: The standard of knowledge about the management of contrast
      media reactions and cardiopulmonary resuscitation among radiologists,
      radiographers and nurses were audited using a two-section questionnaire. Our
      results were compared against nationally accepted standards. Repeat audits were
      undertaken over a 28-month period. Three full audit cycles were completed.
      RESULTS: The initial audit confirmed that although a voluntary training programme
      was in place, knowledge of cardiopulmonary resuscitation techniques were below
      acceptable levels (set at 70%) for all staff members. The mean score for
      radiologists was 50%. Immediate changes instituted included retraining courses,
      the distribution of standard guidelines and the composition and distribution of
      two separate information handouts. Initial improvements were complemented by new
      wallcharts, which were distributed throughout the department, a series of
      lectures on management of contrast reactions and regular reviews with feedback to
      staff. In the third and final audit all staff groups had surpassed the required
      standard. CONCLUSION: Knowledge of contrast media reactions and resuscitation
      needs constant updating. Revision of skills requires a prescriptive programme;
      visual display of advice is a constant reminder. It is our contention all
      radiology departmental staff should consider it a personal duty to maintain their
      resuscitation skills at appropriate standards.

PMID- 11286586
TI  - Malakoplakia of the gall-bladder: imaging and histological features.

PMID- 11286587
TI  - Percutaneous transhepatic use of the hydrolyser thrombectomy catheter to re
      canalize an occluded biliary wallstent.

PMID- 11286588
TI  - Thymic enlargement in an adult following a severe infection.

PMID- 11286589
TI  - Leukoencephalopathy following chemotherapy for colonic carcinoma.

PMID- 11286590
TI  - MRI of Copenhagen's disease in an adult.

PMID- 11286591
TI  - Ultrasound of the testis.

PMID- 11286592
TI  - Palliative treatment of metastatic bone pain by embolization.

PMID- 11286593
TI  - Patients and research.

PMID- 11286594
TI  - Whose interests do lay people represent? Towards an understanding of the role of
      lay people as members of committees.
AB  - Increasingly, lay people are appointed as members to health service committees.
      The term 'lay' is used loosely and the reasons for involving lay people are
      seldom clearly defined. This paper argues that the different roles that lay
      people play need to be explicitly defined in order for their contributions to be
      realized. Although lay members of health service committees are generally assumed
      to be working for patients' interests, our observations lead us to think that
      some lay people tend to support professionals' or managers' interests rather than
      patients' interests as patients would define them. We suggest that lay people
      fall into three broad categories: supporters of dominant (professional)
      interests, supporters of challenging (managerial) interests and supporters of
      repressed (patient) interests. These alignments should be taken into account in
      appointments to health service bodies. Further research is needed on the
      alignments and roles of lay members.

PMID- 11286595
TI  - Developing a prioritisation framework: experiences from a Scottish Health
      Authority.
AB  - OBJECTIVES: To describe the development of the Prioritisation Scoring Index (PSI)
      and its use in a prioritisation framework, providing examples where it has been
      used to prioritise between bids from different specialities and to assist in
      decision-making regarding funding of service developments. To outline lessons
      learned for other health authorities when developing their own prioritisation
      methodologies. BACKGROUND: The PSI was designed for prioritising: investments and
      dis-investments; non-recurring and recurring monies as well as differing
      specialities, care groups and types of intervention. METHODS: The PSI consists of
      a 'basket' of utility criteria and takes account of the numbers of people that
      would receive the proposed intervention and the marginal cost for each additional
      person receiving the intervention. A multidisciplinary panel scored and ranked
      the bids. Two rankings were produced for each intervention according to (1) the
      average panel score for the utility criteria and (2) the cost per additional
      person receiving the intervention. An average of these two rankings produced the
      overall PSI rankings. RESULTS: Almost 200 bids, with a total value of pound 50
      million, were ranked, using the PSI, to prioritise developments worth
      approximately pound 17.5 million that could be funded in a phased implementation
      through the Health Improvement Programme. CONCLUSIONS: Use of the PSI has allowed
      explicit prioritisation of development bids in substantial exercises for both non
      recurring and recurring funding. We describe steps to be considered when other
      health authorities are developing their own prioritisation frameworks.

PMID- 11286596
TI  - Involving consumers in a needs-led research programme: a pilot project.
AB  - OBJECTIVES: To describe the methods used for involving consumers in a needs-led
      health research programme, and to discuss facilitators, barriers and goals.
      DESIGN: In a short action research pilot study, we involved consumers in all
      stages of the Health Technology Assessment (HTA) Programme: identifying and
      prioritizing research topics; commissioning and reporting research; and
      communicating openly about the programme. We drew on the experience of
      campaigning, self-help and patients' representative groups, national charities,
      health information services, consumer researchers and journalists for various
      tasks. We explored consumer literature as a potential source for research
      questions, and as a route for disseminating research findings. These innovations
      were complemented by training, one-to-one support and discussion. A reflective
      approach included interviews with consumers, co-ordinating staff, external
      observers and other programme contributors, document analysis and
      multidisciplinary discussion (including consumers) amongst programme
      contributors. RESULTS: When seeking research topics, face-to-face discussion with
      a consumer group was more productive than scanning consumer research reports or
      contacting consumer health information services. Consumers were willing and able
      to play active roles as panel members in refining and prioritizing topics, and in
      commenting on research plans and reports. Training programmes for consumer
      involvement in service planning were readily adapted for a research programme.
      Challenges to be overcome were cultural divides, language barriers and a need for
      skill development amongst consumers and others. Involving consumers highlighted a
      need for support and training for all contributors to the programme. CONCLUSIONS:
      Consumers made unique contributions to the HTA Programme. Their involvement
      exposed processes which needed further thought and development. Consumer
      involvement benefited from the National Co-ordinating Centre for Health
      Technology Assessment (NCCHTA) staff being comfortable with innovation,
      participative development and team learning. Neither recruitment nor research
      capacity were insurmountable challenges, but ongoing effort is required if
      consumer involvement is to be sustained.

PMID- 11286598
TI  - Citizens' expectations and likely use of a NHS Walk-in Centre: results of a
      survey and qualitative methods of research.
AB  - OBJECTIVES: To find out which groups of people would use a National Health
      Service walk-in centre that would offer mainly health care advice, staffed by
      nurses. To understand the circumstances in which people would use a walk-in
      centre and to ascertain to what extent it would meet patients' expressed health
      care needs. DESIGN: A postal survey of 2400 people plus 27 semi-structured
      interviews and one focus group. SETTING AND PARTICIPANTS: The study was conducted
      in Wakefield, Yorkshire UK, and included both white and ethnic minority groups.
      RESULTS: Most people reported that they would use a walk-in centre. It would be
      more attractive to young as compared with older people, ethnic minority as
      compared with white people, people who are dissatisfied with access to NHS
      services and people with urgent health-care problems. People want a wide range of
      services, including diagnosis, treatment, prevention, and general information.
      People also want access to both doctors and nurses, to male as well as female
      practitioners, to counsellors and interpreters. The type of service planned for
      this walk-in centre will meet some of the expressed needs. However, patients'
      expectations of the walk-in centre exceed planned provision in a number of key
      respects. CONCLUSION: Walk-in centres without GPs and with limited services will
      disappoint the public. It is important that walk-in centres are evaluated and
      attention paid to 'local voices' before additional money is allocated for such
      centres elsewhere.

PMID- 11286597
TI  - What do people with MS want and expect from health-care services?
AB  - OBJECTIVE: To determine the health-care preferences of people with Multiple
      Sclerosis (MS). DESIGN: Cross-sectional survey using a postal questionnaire
      comprising standardized measures of health related quality of life (SF-36) and of
      depression (BDI) and original questions about issues linked to health-care,
      prioritized by people with MS during an earlier qualitative phase. PARTICIPANTS:
      A stratified sample of 318 people with MS in Scotland and England. RESULTS:
      Questionnaires were sent to 471 people with multiple sclerosis. The 318
      respondents (68%) reported a wide variation in quality of life, but on average
      scored significantly lower than normative values in all dimensions of the SF-36.
      The most commonly used home treatment during the previous year was evening
      primrose oil, taken by almost half of the sample (47%). Use of cannabis was
      acknowledged by 8%. There was evidence that many preferences concerning health
      services were not satisfied. For instance lack of advice about at least one MS
      related issue was reported lacking for three-quarters of the sample and 17%
      lacked advice in at least five areas. Advice about exercise was the single most
      requested area. The most frequently consulted health professional was the GP
      (78%) followed by the hospital consultant (50%). The professional that
      respondents most commonly said they would like to have seen was a specialist MS
      nurse (30%). Forty-three percent of the sample said they had attended a special
      meeting for people with MS or disabilities. They were equally divided between
      those who did and who did not find their last attendance helpful. CONCLUSIONS:
      People with MS display a wide variation in their preference for services and
      unmet needs. Information about management (both conventional and unconventional),
      relevant tailored advice and access to appropriately skilled professionals should
      be feasible components of high quality care. This work has highlighted the value
      of involving people with MS in the identification of their preferences; further
      research is needed to show how these might be provided most effectively.

PMID- 11286599
TI  - Women's preferences for discussion of prognosis in early breast cancer.
AB  - OBJECTIVES: To determine preference for prognostic information in women with
      early breast cancer. DESIGN: Cross sectional survey. PARTICIPANTS: 100 women with
      early stage breast cancer attending six teaching hospitals in Sydney, Australia.
      MAIN OUTCOME MEASURES: Women's preference for prognostic information. RESULTS:
      This study identifies new elements to consider in the prognostic consultation.
      Whilst 91% of women wanted to know their prognosis prior to commencing adjuvant
      treatment, 63% wanted their cancer specialist to check with them first before
      giving it. Seventy-seven percent wanted to be asked if they would like a second
      opinion. Seventy-five percent wanted to know about complementary therapies. Most
      wanted their cancer specialist to check their understanding, provide an
      opportunity to ask questions, and explain medical terms (98%). The majority
      wanted information summarized (94%), supported by published information (88%) and
      written down (79%). Ninety-seven percent wanted their fears and concerns listened
      to and 79% wanted emotional support. In addition 80% of women wanted their cancer
      specialist to tell them where they could go to get additional emotional support
      for themselves and their families. Seventy-two percent of women wanted their
      cancer specialist to make sure they had a relative or friend with them.
      CONCLUSIONS: Data from this study suggests that a variety of techniques are
      needed to communicate prognosis. Whilst acknowledging individual women's
      preferences, and not wanting to appear prescriptive, recommendations emerge for
      effective discussion of prognosis with women with early stage breast cancer.

PMID- 11286600
TI  - Conversation analysis: a method for research into interactions between patients
      and health-care professionals.
AB  - BACKGROUND: It is clear that much of the success of health-care provision depends
      on the quality of interactions between health professionals and patients. For
      instance, it is widely recognized that patients are more likely to take
      medication effectively if they have been involved in discussions about treatment
      options, and understand and support the decision about what is prescribed
      (patient concordance). Hence, patient participation is important for the success
      of medical outcomes. The key is to explore how communicative choices made by
      health professionals impact on the quality of interactions in general, and of
      patient participation in particular. However, to date there has not been an
      appropriate method for investigating this connection or impact. OBJECTIVE: To
      outline the perspective and method of Conversation Analysis (CA). Developed
      within sociology and linguistics, CA offers a rigorous method (applicable to
      large data sets) to the study of interaction in health settings. STRATEGY: The
      method of CA is illustrated through a review of CA studies of doctor-patient
      interactions. Two such studies, one from the US and the other from Finland, are
      reviewed, in order to show how CA can be applied to identifying both forms of
      patient participation, and the interactional conditions which provide
      opportunities for patient participation. These studies focus principally on the
      medical examination and diagnostic stages of the consultation. Further research
      will examine the forms and conditions of patient participation in decision
      making.

PMID- 11286601
TI  - Information and involvement.
AB  - This article discusses the beliefs that provision of good quality information is
      the key to (a) successful and satisfying involvement of patients in their own
      decision-making and (b) involvement of lay people in the research process, in
      debate and other involvement in wider health issues. Education of children,
      health professionals, the public and the media is advocated, enabling critical
      appraisal skills and good quality health information to lead to improved
      involvement of citizens in health-care decisions of all kinds, both individual
      and societal. Examples of individual, group and specific group involvement
      through research projects, debates about screening, Citizens' Juries, etc. are
      used to illustrate benefits to patients and to health provision in general.

PMID- 11286602
TI  - Beta-blockers in heart failure. 2. Mode of action.

PMID- 11286603
TI  - Consensus methods in prescribing research.

PMID- 11286604
TI  - Cardiac natriuretic peptides--hope or hype?
AB  - In recent years, biomedical science has witnessed the emergence of peptide
      biochemicals as significant topics of research. Some of these peptides are of
      little potential clinical use, while others, of which cardiac natriuretic
      peptides are an example, appear to be promising. This particular group of
      peptides (i.e. ANP, BNP and CNP) shows promising diagnostic as well as
      therapeutic potential for various pathological conditions. In the case of acute
      myocardial infarction, these peptides have significant diagnostic and predictive
      properties, more so than other biochemicals such as adrenaline, renin and
      aldosterone. In addition, ANP is found to have significant benefits over the
      classical anti-anginal drug glyceryl trinitrate. However, as is the case with
      other peptides, applying these benefits clinically may not be easy because of the
      structure of the compounds, but various strategies are now being applied to solve
      this problem. These include the use of non-peptide receptor ligands, inhibitors
      of ANP metabolism, gene therapy and so on. The development of drugs in clinical
      practice, which exploits the natriuretic peptides system therefore seems to be
      promising, and this article reviews advances in our understanding of these
      compounds.

PMID- 11286605
TI  - Rational pharmacotherapy of hypertension in the elderly: analysis of the choice
      and dosage of drugs.
AB  - OBJECTIVES: To determine in older people with uncomplicated hypertension: (a) the
      pattern of prescribing of antihypertensives; (b) the extent of physicians'
      adherence to recommendations on dosage for antihypertensive combinations; (c)
      whether prescribing practice conforms with recommended therapeutic guidelines;
      and (d) the frequency of prescribing of other drugs which have the potential to
      alter the efficacy of antihypertensive agents. METHODS: A survey of prescribing
      in older patients with uncomplicated hypertension in primary care setting of
      Bahrain was conducted. RESULTS: Of the 432 (56.5%) patients on monotherapy, 192
      (44.4%) were treated with beta-blockers, 87 (20.1%) with calcium channel blockers
      (CCBs), 53 (12.3%) with alpha-methyldopa, 47 (10.9%) with diuretics, 46 (10.6%)
      with angiotensin converting enzyme (ACE) inhibitors, and 7 (1.6%) with
      hydralazine. Of the 1146 patients on mono- or combination therapies, 434 (56.8%)
      were treated with beta-blockers, 244 (31.9%) with diuretics, 211 (27.6%) with
      CCBs, 139 (18.2%) with ACE inhibitors, 103 (13.5%) with alpha-methyldopa 8 (1.0%)
      with brinerdine and 7 (0.9%) with hydralazine. In the 332 (43.5%) patients on
      combination therapy, 15 different two- and three-antihypertensive drug
      combinations were prescribed: a diuretic with a beta-blocker (37.2%) and a beta
      blocker with either a CCB (20.9%) or an ACE inhibitor (12.4%) were the most
      popular two-drug regimens. The most commonly prescribed triple drug regimens were
      a diuretic and a beta-blocker plus either a CCB (26.1%) or an ACE inhibitor
      (17.4%) and diuretic plus an ACE inhibitor and a CCB (15.2%). Daily dosage of
      beta-blockers, ACE inhibitors and alpha-methyldopa were somewhat high in a
      considerable proportion of patients on both mono- and combined therapies. A
      substantial proportion (9.7%) of patients on monotherapy were treated with
      immediate release nifedipine. CONCLUSION: The pharmacotherapy of hypertension in
      elderly patients was found in some instances not to conform to recommended
      guidelines. For certain classes of antihypertensive agent such as beta-blockers,
      ACE inhibitors and alpha-methyldopa, neither the principles of geriatric
      pharmacology nor of antihypertensive combination therapy, and in particular, the
      need to reduce daily dosage, were followed. The use of immediate release
      nifedipine in the elderly is irrational, and instead, the use of long-acting
      dihydropyridine CCBs should be considered. The results of long-term randomized
      clinical trials published during the last decade have had a minimal impact on
      clinical practice of primary care physicians in Bahrain.

PMID- 11286606
TI  - Comparative in vitro and in vivo study of a sugar-coated chloroquine preparation
      marketed in Tanzania versus an ordinary brand.
AB  - OBJECTIVE: To investigate the absorption and the quality of a sugar-coated
      chloroquine (CQ) marketed in Tanzania. METHOD: Twenty healthy volunteers were
      randomised to take either the test brand (group A) or a control chloroquine
      phosphate (group B). Each subject received 300 mg chloroquine base. Whole blood
      dried on filter papers were collected at time 0 and at 15 and 30 min and at 1, 2,
      3, 4, 6, 8, 24, 36, 48, 72 and 168 h after drug intake. Urine samples were
      collected at time 0, 0-4 h, 4-8 h, 8-24 h, 24-48 h and 48-72 h after drug
      administration. In an in vitro study, six tablets from each of the two CQ
      preparations were checked for the amount of active drug contained in each tablet
      and their dissolution rates. RESULTS: The blood concentration Area Under the
      Curve (AUC) of group B was about 10% larger than that of group A. The total
      amounts of CQ plus deethylchloroquine excreted with the urine during the 72-h
      study period were 5% for group A and 6% for group B. None of the pharmacokinetic
      parameters were significantly different between the two groups. All the tablets
      contained the labelled amount of chloroquine; however, one tablet from the test
      drug failed to fulfil the required dissolution rate. CONCLUSION: We found no
      major difference between the AUCs of the two CQ preparations, but the sugar
      coated brand has shown to have variable dissolution rate.

PMID- 11286607
TI  - Enteral suspension of nifedipine for neonates. Part 1. Formulation of nifedipine
      suspension for hospital use.
AB  - OBJECTIVE: To formulate an oral suspension of nifedipine for paediatric use and
      to assess its content uniformity as well as the microbiological and physical
      stabilities of the hypromellose solution that was used in the formulation.
      METHOD: Six concentrations (0.5-3.0%) of hypromellose colloids and water as a
      blank were compounded with nifedipine, both as a powder and as crushed tablets,
      to a concentration of 1 mg/mL. Four different screening tests were used to find
      the most homogenous and dose-accurate combination. First, nifedipine suspensions
      were stored in vials for one month and visual homogenity of the redispersed
      suspensions was observed. Second, the homogenity of the suspensions was studied
      by measuring the nifedipine concentration from upper, middle and lower parts of
      the redispersed suspension. Next, the nifedipine concentration was measured from
      the suspensions immediately, 1 min and 2 min after shaking to ensure dose
      accuracy during the administration period. Finally, suspensions were packaged
      into oral disposable syringes and nifedipine concentrations were determined after
      one month of storage. Content uniformity of the packaged single-dose syringe
      suspensions was studied according to a method established by the European
      Pharmacopoeia. Microbiological stability, density, pH, osmolality, viscosity and
      surface tension of the hypromellose solution were studied over a 12-month storage
      period. RESULTS: From the results of the screening tests of hypromellose
      solution, 1.0% hypromellose was chosen as the vehicle for nifedipine enteral
      suspensions, made from both crushed tablets and nifedipine powder. Nifedipine
      suspensions made from hypromellose 1.0% were easiest to redisperse as a
      homogenous solution, and it also appeared best on visual inspection. The content
      uniformity of the suspension complied with the test recommended by the European
      Pharmacopoeia. The 1.0% hypromellose solution was found to be microbiologically
      stable for 6 months and physically stable for 12 months.

PMID- 11286608
TI  - Enteral suspension of nifedipine for neonates. Part 2. Stability of an
      extemporaneously compounded nifedipine suspension.
AB  - OBJECTIVE: To investigate the chemical, microbiological and physical stability of
      an extemporaneously prepared nifedipine oral suspension, packaged in disposable
      syringes and prepared in a hospital pharmacy for paediatric use. METHODS: Two
      different suspensions were prepared, from nifedipine tablets and drug powder, by
      using an autoclaved 1.0% solution of hypromellose as the vehicle. The final
      theoretical drug concentration was 1 mg/mL. Doses of 1.0 ml were packaged into a
      2 ml syringe with a cap. Nifedipine suspensions were stored under three
      conditions: at room temperature (22 degrees C), in a refrigerator (6 degrees C)
      protected from light, and at room temperature (22 degrees C) exposed to
      artificial daylight (400 lux) under controlled circumstances. The nifedipine
      concentration was measured in suspensions protected from light on days 0, 1, 3,
      5, 7, 14, 21 and 28, and in suspensions exposed to light at 0, 3, 6, 18 and 24 h,
      and on days 2, 3, 5 and 7 after preparation. Nifedipine was analysed by a
      reproducible and validated stability-indicating HPLC-method. Microbiological and
      physical stability of the nifedipine suspension samples protected from light were
      examined for 28 days. RESULTS: Mean nifedipine concentration remained over 90% of
      the initial concentration throughout the 4-week study period in light-protected
      unit-dose suspensions, prepared from either crushed tablets or drug powder with
      hypromellose 1.0%. When exposed to light, however, nifedipine decomposed rapidly.
      Photodegradation of nifedipine exceeded 25% within 3 h and was essentially
      complete within 7 days. CONCLUSION: In the University Hospital of Kuopio,
      newborns have been treated with nifedipine suspension prepared from tablets, and
      preliminary experiences with administration of suspension have been encouraging.
      It may also be possible to apply this methodology to other medicines used in
      paediatrics.

PMID- 11286609
TI  - Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects
      aspect: a double-blind randomized controlled trial.
AB  - OBJECTIVE: Baclofen is known for the alleviation of signs and symptoms of
      spasticity. Reports from our previous study have suggested that it may be at
      least as effective as clonidine in the management of physical symptoms of opiate
      withdrawal syndromes and superior to clonidine in the management of mental
      symptoms. We now report on a randomized double-blind comparison of baclofen vs.
      clonidine in view of side-effects profile. METHODS: A total of 62 opiates addicts
      were randomly assigned to treatment with baclofen or clonidine during a 14-day,
      double-blind clinical trial. All patients met the DSM IV criteria for opioid
      dependence. Maximum daily doses were 40 mg for baclofen and 0.8 mg for clonidine.
      This trial medication was given three times per day in divided doses. The
      severity of side-effects was measured in days 0, 1, 2, 3, 4, 7 and 14. RESULTS:
      There was no significant difference between two treat7ments in terms of retention
      in treatment (dropout) and overall side-effect. Nevertheless, significantly more
      problems relating to hypotension were encountered with subjects on clonidine.
      CONCLUSION: We conclude that, the low incidence of hypotension with baclofen
      suggests that the drug may be suitable for outpatient ambulatory treatment of
      withdrawal from opiates.

PMID- 11286610
TI  - Adherence with naltrexone prescription advice in hospital outpatient alcohol
      rehabilitation programme.
AB  - BACKGROUND: The anti-craving drug, naltrexone, is used as a pharmacotherapeutic
      adjunct in the treatment of alcohol dependence. In addictive disorders,
      compliance issues remain central. There are limited data on compliance with
      naltrexone treatment regimens within formalized rehabilitation programs and even
      less data that identifies factors that have an impact on this. OBJECTIVE: To
      study patient adherence to naltrexone medication regimens and examine whether
      patients' reported pre-treatment alcohol use, dependence severity and measures of
      psychological health are predictive of medication compliance. METHOD: Fifty
      outpatients meeting DSM IV criteria for alcohol dependence enrolled in a 12-week
      rehabilitation programme. This included cognitive behavioural therapy (CBT) and
      naltrexone, 50 mg orally daily. Measures included: pharmacy prescription pick-up
      including number of tablets dispensed, programme attendance and patient pre
      treatment alcohol use variables. Measures of psychological health included
      somatic symptoms, anxiety, social dysfunction and depression as measured by the
      General Health Questionnaire (GHQ-28). RESULTS: Classifying the sample into
      compliant (> or = 90% medication pick-up) and less compliant groups, 66% of
      subjects were naltrexone-compliant. Pre-treatment alcohol use variables were not
      predictive of compliance. Although social dysfunction and depression tended
      towards poorer prescription filling, measures of psychological distress (GHQ-28)
      did not identify factors predictive of medication non-compliance. One patient
      withdrew from treatment because of naltrexone-induced dysphoria. CONCLUSION:
      Patients with alcohol dependence demonstrated high levels of anti-craving
      medication compliance, good rehabilitation programme participation and favourable
      outcomes. Naltrexone was well tolerated. Medication compliance in this study
      group compared well with those of other hospital populations with chronic
      disorders. Factors predictive of anti-craving medication compliance in alcohol
      dependence require further study.

PMID- 11286612
TI  - Pemphigus: is there another half of the story?

PMID- 11286613
TI  - Calcium regulates the expression of insulin-like growth factor binding protein-3
      by the human keratinocyte cell line HaCaT.
AB  - The insulin-like growth factor (IGF) system is essential for epidermal
      homeostasis. Insulin-like growth factor binding protein 3 (IGFBP-3), a modulator
      of IGF action that also exhibits IGF-independent activity, is localized to
      selected keratinocytes in the basal epidermal layer and may thus contribute to
      keratinocyte differentiation. We have utilized the human keratinocyte cell line,
      HaCaT, to examine the effect of calcium on the regulation of components of the
      IGF system. Western ligand and northern blot analyses revealed secreted IGFBP-3
      and IGFBP-3 mRNA were reduced by an elevation in calcium levels in the culture
      medium. At 1.0 and 1.2 mM CaCl2 culture conditions IGFBP-3 abundance was reduced
      to 36% +/- 1.6% and 26% +/- 7.1%, respectively, of that from cells grown at 0.03
      mM CaCl2. IGFBP-3 mRNA levels in 0.7 mM and 1.2 mM CaCl2 were reduced to 46% +/-
      17.4% and 24% +/- 4.6%, respectively, compared with IGFBP-3 mRNA levels at 0.03
      mM CaCl2. The observed reduction of IGFBP-3 was not associated with IGFBP-3
      proteolysis. In contrast IGF-I receptor protein and mRNA levels remained
      unchanged. The IGF-I stimulated proliferative response of HaCaT keratinocytes
      showed that under low (0.03 mM) and high (1.2 mM) CaCl2 conditions IGF-I at 100
      and 1000 ng per ml similarly increased cell number 2.4- and 2.7-fold,
      respectively, with similar dose-response curves. HaCaT keratinocytes grown under
      medium (0.7 mM) and high (1.2 mM), but not low (0.03 mM), CaCl2 conditions for 21
      d revealed an induction of profilaggrin mRNA, a marker of keratinocyte
      differentiation. These studies indicate that the exposure of HaCaT keratinocytes
      to elevated calcium levels is associated with a decline in IGFBP-3 but not IGF-I
      receptor levels. These findings suggest a potential mechanism for the
      distribution of IGFBP-3 in the epidermis, which may be involved in the process of
      keratinocyte differentiation.

PMID- 11286615
TI  - Clonal nature of seborrheic keratosis demonstrated by using the polymorphism of
      the human androgen receptor locus as a marker.
AB  - We evaluated the clonality of seborrheic keratoses using a polymorphism due to
      the random inactivation of one of two X chromosomes in females. Thirty-eight
      seborrheic keratoses obtained from the skin of females with polymorphism of the
      human androgen receptor (HUMARA) locus were examined by a fluorescent polymerase
      chain reaction procedure, which allowed accurate measurement of the peak
      intensities of each HUMARA allele. The epithelial portion of seborrheic keratosis
      and normal control epidermis adjacent to the seborrheic keratosis were removed by
      laser capture microdissection. As biopsied specimens of seborrheic keratoses
      contained small amounts of normal epidermis, the effect of digestion by a
      restriction enzyme (HhaI) recognizing the nonmethylated active sites was compared
      between seborrheic keratoses and normal control epidermis in only five seborrheic
      keratosis cases. Disappearance or significant reduction in intensity of one of
      two HUMARA alleles was observed after HhaI digestion in seborrheic keratoses, but
      not in the normal control epidermis. Although the skewing of the polymorphism was
      not corrected by the normal control epidermis in the remaining 33 seborrheic
      keratosis cases, one of two HUMARA peaks practically disappeared after HhaI
      digestion in 20 of 33 seborrheic keratosis cases. In total, 25 of 38 seborrheic
      keratoses were considered to be monoclonal. The histologic type of seborrheic
      keratoses did not affect clonality.

PMID- 11286614
TI  - Detection of mRNA for eotaxin-2 and eotaxin-3 in human dermal fibroblasts and
      their distinct activation profile on human eosinophils.
AB  - As many new biologically active chemokines have been cloned exploring the genomic
      DNA sequence database in the vicinity of already known chemokine sequences
      without demonstrating their natural origin, it is important to transfer findings
      from in vitro experiments with chemokines into the in vivo situation. With
      respect to eosinophils and fibroblasts that play an important part in the
      pathogenesis of allergic and autoimmune diseases, the role of the recently
      discovered members of the eotaxin family, eotaxin-2 and eotaxin-3, is not really
      understood. In order to elucidate the origin and biologic potency of the eotaxin
      family this study was performed. Conventional reverse transcription-polymerase
      chain reaction analysis was suitable to detect mRNA for eotaxin and eotaxin-3 but
      not for eotaxin-2 in dermal fibroblasts. In contrast to conventional reverse
      transcription-polymerase chain reaction, LightCycler analysis revealed that
      dermal fibroblasts constitutively expressed mRNA not only for eotaxin and eotaxin
      3 but also for eotaxin-2. Moreover, with this technique we investigated mRNA
      expression levels after stimulation of fibroblasts with interleukin-4 and
      interleukin-4 plus tumor necrosis factor-alpha: the rank order of expression
      levels within the eotaxin family was eotaxin > eotaxin-3 > eotaxin-2. To address
      the question of the efficacy of eotaxin-3, we compared its activity with eotaxin,
      eotaxin-2, monocyte chemotactic protein-3, monocyte chemotactic protein-4, and
      RANTES in different test systems for eosinophils. The efficacy of the CC
      chemokines at equimolar concentrations with respect to the chemotactic response
      of human eosinophils was eotaxin-3 = eotaxin = eotaxin-2 > RANTES > monocyte
      chemotactic protein-4. The rank order of activity with respect to actin
      polymerization and release of toxic reactive oxygen species was eotaxin-3 =
      eotaxin = eotaxin-2 and eotaxin = eotaxin-2 > eotaxin-3 = monocyte chemotactic
      protein-3 = monocyte chemotactic protein-4 = RANTES, respectively. This study
      indicated a distinct profile in expression levels of the members of the eotaxin
      family in dermal fibroblasts. Indeed, all three eotaxin ligands demonstrated
      activation of human eosinophils with similar efficacies for chemotaxis,
      cytoskeletal rearrangements, activation of Gi proteins and transients of [Ca2+]i,
      but a distinct profile of activity with respect to the binding to CCR3 and the
      release of toxic reactive oxygen species. These findings may help to understand
      further the role of CC chemokines in fibroblast/eosinophil activation, which is
      of interest particularly in allergic and autoimmune diseases.

PMID- 11286616
TI  - Evidence for novel functions of the keratin tail emerging from a mutation causing
      ichthyosis hystrix.
AB  - Unraveling the molecular basis of inherited disorders of epithelial fragility has
      led to understanding of the complex structure and function of keratin
      intermediate filaments. Keratins are organized as a central alpha-helical rod
      domain flanked by nonhelical, variable end domains. Pathogenic mutations in 19
      different keratin genes have been identified in sequences corresponding to
      conserved regions at the beginning and end of the rod. These areas have been
      recognized as zones of overlap between aligned keratin proteins and are thought
      to be crucial for proper assembly of keratin intermediate filaments.
      Consequently, all keratin disorders of skin, hair, nail, and mucous membranes
      caused by mutations in rod domain sequences are characterized by perinuclear
      clumping of fragmented keratin intermediate filaments, thus compromising
      mechanical strength and cell integrity. We report here the first mutation in a
      keratin gene (KRT1) that affects the variable tail domain (V2) and results in a
      profoundly different abnormality of the cytoskeletal architecture leading to a
      severe form of epidermal hyperkeratosis known as ichthyosis hystrix Curth
      Macklin. Structural analyses disclosed a failure in keratin intermediate filament
      bundling, retraction of the cytoskeleton from the nucleus, and failed
      translocation of loricrin to the desmosomal plaques. These data provide the first
      in vivo evidence for the crucial role of a keratin tail domain in supramolecular
      keratin intermediate filament organization and barrier formation.

PMID- 11286617
TI  - 2-Nonenal newly found in human body odor tends to increase with aging.
AB  - Human body odor consists of various kinds of odor components. Here, we have
      investigated the changes in body odor associated with aging. The body odor of
      subjects between the ages of 26 and 75 was analyzed by headspace gas
      chromatography/mass spectrometry. 2-Nonenal, an unsaturated aldehyde with an
      unpleasant greasy and grassy odor, was detected only in older subjects (40 y or
      older). Furthermore, analysis of skin surface lipids revealed that omega7
      unsaturated fatty acids and lipid peroxides also increased with aging and that
      there were positive correlations between the amount of 2-nonenal in body odor and
      the amount of omega7 unsaturated fatty acids or lipid peroxides in skin surface
      lipids. 2-Nonenal was generated only when omega7 unsaturated fatty acids were
      degraded by degradation tests in which some main components of skin surface
      lipids were oxidatively decomposed using lipid peroxides as initiator of an
      oxidative chain reaction. The results indicate that 2-nonenal is generated by the
      oxidative degradation of omega7 unsaturated fatty acids, and suggest that 2
      nonenal may be involved in the age-related change of body odor.

PMID- 11286618
TI  - An autocrine loop mediates expression of vascular endothelial growth factor in
      human dermal microvascular endothelial cells.
AB  - The expression of vascular endothelial growth factor mRNA and protein is
      regulated by a number of agents including growth factors, cytokines, and phorbol
      esters. Here we report that vascular endothelial growth factor is able to
      increase its own level in cultured human dermal microvascular endothelial cells.
      Accumulation of vascular endothelial growth factor mRNA and polypeptide can be
      detected as early as 4 h after addition of vascular endothelial growth factor to
      the cell culture medium. The autocrine action of vascular endothelial growth
      factor appears to be mediated by the KDR receptor. The increase of its own
      message by vascular endothelial growth factor is blocked by the transcription
      inhibitor actinomycin D. Transient transfection experiments performed with human
      dermal microvascular endothelial cells and using a 3.2 kb human vascular
      endothelial growth factor promoter fragment showed that vascular endothelial
      growth factor auto-induction can be mimicked at the promoter level. This
      indicates that the observed vascular endothelial growth factor mRNA increase
      after vascular endothelial growth factor treatment is occurring at the level of
      transcription. Furthermore, vascular endothelial growth factor auto-induction is
      inhibited by PD 098059, showing that phosphorylation events, catalyzed by mitogen
      activated protein kinases, are a prerequisite for the vascular endothelial growth
      factor effect. Examination of extracellular signal-regulated kinase and c-Jun N
      terminal protein kinase catalytic activities showed that both enzymes have to be
      activated to mediate the vascular endothelial growth factor signal. Our data
      demonstrate for the first time the existence of an autocrine loop for vascular
      endothelial growth factor in endothelial cells. Most probably this represents an
      amplification mechanism for the action of vascular endothelial growth factor in
      the microvascularization process.

PMID- 11286619
TI  - Contact-free spectroscopy of leg ulcers: principle, technique, and calculation of
      spectroscopic wound scores.
AB  - Objective wound monitoring is an essential tool for evidence-based medicine in
      leg ulcers and other chronic wounds. Non-invasive and contact-free optical
      remittance spectroscopy seems to be a useful approach as it can provide
      additional information with respect to more traditional techniques of wound
      scoring. Twenty-three patients with chronic venous, arterial, and mixed leg
      ulcers were enrolled in this study. The clinical state of the ulcers was
      documented by a clinical wound score (quantity, color, and consistency of
      granulation tissue). The spectroscopic readings were performed with a novel diode
      array spectrometer system in the visible and near-infrared range of the spectrum
      (400-1600 nm) with a resolution of 5 nm. The wound spectra mainly depend on the
      absorption of hemoglobin and water. The maximum correlation coefficients of mean
      remittance spectra with the clinical wound scores did not exceed +/- 0.5.
      Discriminant and cluster analysis were applied for spectral classification of
      wound scores. By using cross-validation the percentage of correct predicted wound
      scores was about 69%. Our results indicate that the application of optical
      visible and near-infrared spectroscopy could be a valuable remedy for the
      clinician.

PMID- 11286620
TI  - Autofluorescence of human skin is age-related after correction for skin
      pigmentation and redness.
AB  - When measuring the skin fluorescence in vivo, the absorption of chromophores such
      as melanin and hemoglobin often contribute predominantly to the changes in
      fluorescence and obscure the information from the fluorophores. We measured in
      vivo the collagen-linked 375 nm fluorescence (excitation: 330 nm) and 455 nm
      fluorescence (excitation: 370 nm) from nonexposed buttock skin of healthy
      volunteers. Skin pigmentation and redness of the same sites were quantified by
      reflectance of the skin at 555 nm and 660 nm. Multiple regression analysis was
      used to find the correlation between the fluorescence and skin pigmentation and
      redness. The fluorescence was corrected for the impact of pigmentation and
      redness according to the equation found in the regression analyses. The age
      related trend of the fluorescence was evaluated. The 375 nm fluorescence showed
      positive relation to age, whereas the 455 nm fluorescence showed no significant
      relation to age. The increasing rate of the 375 nm fluorescence (logarithm
      transformed) was 2% per year, which is comparable with previously published data.
      The results suggest that the correction of the autofluorescence intensity for
      skin pigmentation and redness is valid, and the 375 nm skin autofluorescence may
      be used as a biologic marker of skin aging in vivo.

PMID- 11286621
TI  - Expression of multiple cytochrome p450 enzymes and multidrug resistance
      associated transport proteins in human skin keratinocytes.
AB  - Cytochrome P450 enzymes metabolize various endogenous and exogenous small
      molecular weight compounds. Transport-associated proteins, such as P
      glycoprotein, multidrug resistance-associated protein and lung resistance protein
      are overexpressed in drug-resistant cell lines, as well as in human tumors from
      various histologic origins, including malignant melanoma. Little is known about
      the expression and function of cytochrome enzymes and multidrug resistance
      associated transport proteins in human skin; therefore, the aim of this study was
      to analyze the expression pattern of cytochrome enzymes and multidrug resistance
      associated transport proteins in proliferating human epidermal keratinocytes
      under constitutive conditions and after induction with various inducers. Reverse
      transcription-polymerase chain reaction revealed constitutive expression of
      cytochromes 1A1, 1B1, 2B6, 2E1, and 3A5 in keratinocytes and showed expression of
      cytochrome 3A4 after incubation with dexamethasone. The expression of cytochrome
      1A1 was enhanced on the mRNA level after induction with benzanthracene. Reverse
      transcription-polymerase chain reaction analysis of the multidrug resistance
      associated transport proteins revealed constitutive expression of multidrug
      resistance-associated proteins 1 and 3-6, and lung resistance protein in human
      epithelial keratinocytes and was negative for multidrug resistance 1 and 2.
      Expression of 1 was seen after induction with dexamethasone. Reverse
      transcription-polymerase chain reaction results were confirmed by immunoblots
      which showed expression of cytochromes 1A1, 2B6, 2E1, and 3A, multidrug
      resistance-associated proteins 1, 3, and 5 as well as multidrug resistance 1
      after induction with dexamethasone. Immunohistology showed positive
      immunofluorescence in skin specimens for cytochromes 1A1, 2B6, 2E1, and 3A and
      multidrug resistance-associated protein 1 and multidrug resistance 1.
      Constitutive activity of cytochrome 1A1, 2B, 2E1, and 3A enzymes was measured by
      catalytic assays. These results show that keratinocytes of the human skin express
      various transport-associated enzymes and detoxifying metabolic enzymes. Previous
      studies have revealed that cytochrome enzymes and transport-associated proteins
      play complementary parts in drug disposition by biotransformation (phase I) and
      anti-transport (phase III) and act synergistically as a drug bioavailability
      barrier.

PMID- 11286622
TI  - Characterization of the CC chemokine receptor 3 on human keratinocytes.
AB  - CC chemokine receptors are expressed on hematopoietic cells, and these may impart
      selective homing of monocyte, leukocyte, and lymphocyte subsets to sites of
      inflammation. CC chemokine receptor 3 is the major receptor on eosinophils and is
      also expressed on other inflammatory cells suggesting its important role for
      allergic diseases such as atopic dermatitis and bronchial asthma. Eotaxin,
      eotaxin-2 and eotaxin-3 have been identified as ligands that only activate CC
      chemokine receptor 3. CC chemokine receptor 3 is also activated by other
      promiscuous ligands, however, such as RANTES and monocyte chemotactic protein 4.
      To date, CC chemokine receptor 3 has not been reported to be expressed on
      nonhematopoietic cells. In this study, we investigated whether keratinocytes
      possess autocrine and paracrine mechanisms for CC chemokine secretion and
      receptor expression as reported for the expression of interleukin 8 and its
      receptors. Reverse transcriptase polymerase chain reaction analysis demonstrated
      that CC chemokine receptor 3 mRNA is expressed constitutively in cultured
      keratinocytes. The signal quantities of the CC chemokine receptor 3 amplicons
      showed lower intensities for keratinocytes than for eosinophils. In situ
      hybridization techniques exhibited that basal cell layers of the epidermis were
      stained homogeneously for CC chemokine receptor 3 mRNA with a decreasing signal
      to the upper epidermis showing that differentiating and proliferating
      keratinocytes did express mRNA specific for CC chemokine receptor 3.
      Immunohistochemical studies confirmed low expression of CC chemokine receptor 3
      protein on epidermal keratinocytes compared to the high level observed on
      infiltrating eosinophils. Furthermore, stimulation of cultured keratinocytes with
      eotaxin resulted in an increased [3H]thymidine incorporation indicating a role of
      CC chemokine receptor 3 in epidermal proliferation and differentiation. These
      data demonstrate that CC chemokine receptor 3 is expressed not only on
      hematopoietic cells but also on keratinocytes as nonhematopoietic cells with
      ectodermal origin. Therefore, the identification of CC chemokine receptor 3 on
      epidermal keratinocytes may indicate a role for CC chemokine receptor 3 and its
      ligands in skin physiology and pathophysiology.

PMID- 11286623
TI  - Paraneoplastic pemphigus sera react strongly with multiple epitopes on the
      various regions of envoplakin and periplakin, except for the c-terminal
      homologous domain of periplakin.
AB  - Paraneoplastic pemphigus sera react with multiple plakin family proteins, among
      which only envoplakin and periplakin are constantly detected by immunoblotting
      using normal human epidermal extracts. Using bacterial expression vectors
      containing polymerase chain reaction-amplified cDNA, we have prepared variously
      truncated recombinant glutathione-S-transferase-fusion proteins of envoplakin and
      periplakin, which presented N-terminal, central and C-terminal domains of each
      protein, as well as the so-called C-terminal homologous domain of envoplakin and
      the junctional regions of these domains. By immunoblotting using these 11
      recombinant proteins, we demonstrated that most of the 26 paraneoplastic
      pemphigus sera reacted very strongly with multiple recombinant proteins of
      envoplakin and periplakin, except for the C-terminal homologous domain of
      periplakin. We also examined the reactivity with these recombinant proteins of
      other blistering diseases, including pemphigus vulgaris, pemphigus foliaceus, and
      bullous pemphigoid, and found that a few nonparaneoplastic pemphigus sera showed
      a weak reactivity with some of the recombinant proteins. Interestingly, some sera
      showed relatively strong reactivity with the C-terminal homologous domain of
      periplakin to which paraneoplastic pemphigus sera reacted less frequently. These
      results indicate that, although nonparaneoplastic pemphigus sera occasionally
      show a weak reactivity with envoplakin and periplakin, the pathogenicity and the
      mechanism of antibody production in these cases may be different from those in
      paraneoplastic pemphigus.

PMID- 11286624
TI  - Expression, candidate gene, and population studies of the melanocortin 5
      receptor.
AB  - In mouse the melanocortin 5 receptor is known to regulate sebaceous gland
      function. To clarify its role in man, we have studied melanocortin 5 receptor
      expression in skin, and allelic variation at the melanocortin 5 receptor locus in
      diverse human populations and candidate disease groups. Melanocortin 5 receptor
      protein and mRNA expression were studied by immunohistochemistry and reverse
      transcriptase polymerase chain reaction. Melanocortin 5 receptor mRNA was
      detected in normal skin and cultured keratinocytes but not in cultured
      fibroblasts or melanocytes. Immunohistochemistry revealed melanocortin 5 receptor
      immunoreactivity in the epithelium and appendages, including the sebaceous gland,
      eccrine glands, and apocrine glands, as well as low level expression in the
      interfollciular epidermis. In order to screen for genetic diversity in the
      melanocortin 5 receptor that might be useful for allelic association studies we
      sequenced the entire melanocortin 5 receptor coding region in a range of human
      populations. One nonsynonymous change (Phe209Leu) and four synonymous changes
      (Ala81Ala, Asp108Asp, Ser125Ser, and Thr248Thr) were identified. Similar results
      were found in each of the populations except for the Inuit in which only the
      Asp108Asp variant was seen. The apparent "global distribution" of melanocortin 5
      receptor variants may indicate that they are old in evolutionary terms. Variation
      of melanocortin 5 receptor was examined in patients with acne (n = 21),
      hidradenitis supprativa (n = 4), and sebaceous gland lesions comprising sebaceous
      nevi, adenomas, and hyperplasia (n = 13). No additional mutations were found. In
      order to determine the functional status of the Phe209Leu change, increase in
      cAMP in response to stimulation with alpha-melanocyte-stimulating hormone was
      measured in HEK-293 cells transfected with either wild-type or the Phe209Leu
      variant. The variant melanocortin 5 receptor was shown to act in a concentration
      dependent manner, which did not differ from that of wild type. We have therefore
      found no evidence of a causative role for melanocortin 5 receptor in sebaceous
      gland dysfunction, and in the absence of any association between variation at the
      locus and disease group, the pathophysiologic role of the melanocortin 5 receptor
      in man requires further study.

PMID- 11286625
TI  - The role of the epidermal endothelin cascade in the hyperpigmentation mechanism
      of lentigo senilis.
AB  - Little is known about the mechanism(s) underlying hyperpigmentation in lentigo
      senilis. We have previously reported that keratinocyte-derived endothelins are
      intrinsic paracrine mitogens and melanogens for human melanocytes and that they
      play an essential role in stimulating ultraviolet-B-induced melanogenesis. In
      this study, we have used immunohistochemistry and reverse transcriptase
      polymerase chain reaction analysis to clarify the role of the endothelin cascade,
      including endothelin production, processing by endothelin-converting enzyme, and
      expression of the endothelin B receptor, in the hyperpigmentary mechanism(s)
      involved in lentigo senilis. The number of tyrosinase immunopositive melanocytes
      in lentigo senilis lesional skin was increased 2-fold over the perilesional
      epidermis. Immunohistochemistry using antibodies to endothelin-1 demonstrated
      relatively stronger staining in the lesional epidermis than in the perilesional
      epidermis. Reverse transcriptase polymerase chain reaction analysis concomitantly
      demonstrated accentuated expression of transcripts for endothelin-1 and for the
      endothelin B receptor in lentigo senilis lesional skin, which was accompanied by
      a similar accentuated expression of tyrosinase mRNA compared with the
      perilesional control. The endothelin-1-inducible cytokine, tumor necrosis factor
      alpha, was consistently upregulated in the lentigo senilis lesional epidermis as
      determined at the transcriptional level and by immunostaining, whereas
      interleukin-1alpha was downregulated. In contrast, endothelin-converting enzyme
      1alpha mRNA was not substantially increased in the lesional epidermis. These
      findings suggest that an accentuation of the epidermal endothelin cascade,
      especially with respect to expression of endothelin and the endothelin B
      receptor, plays an important role in the mechanism involved in the
      hyperpigmentation of lentigo senilis.

PMID- 11286626
TI  - The paracrine role of stem cell factor/c-kit signaling in the activation of human
      melanocytes in ultraviolet-B-induced pigmentation.
AB  - The interaction of stem cell factor with its receptor, c-kit, is well known to be
      critical to the survival of melanocytes. Little is known about the role(s) of the
      stem cell factor/c-kit interaction in epidermal pigmentation, however. To clarify
      whether the stem cell factor/c-kit signaling has a paracrine role in ultraviolet
      B-induced pigmentation, we determined whether the exposure of human
      keratinocytes, melanocytes, and the epidermis to ultraviolet B light stimulates
      the expression of stem cell factor or c-kit at the gene and/or protein levels. We
      further examined whether interrupting the binding of stem cell factor to c-kit by
      subepidermal injection of a monoclonal antibody to c-kit affects ultraviolet-B
      induced pigmentation in brownish guinea pig skin. When human keratinocytes and
      melanocytes in culture were exposed to ultraviolet B light, transcripts of stem
      cell factor and c-kit (as assessed by reverse transcription polymerase chain
      reaction) and expression of those proteins (by enzyme-linked immunosorbent assay
      and western blotting) increased significantly and peaked at a dose of 20-40 mJ
      per cm2. In ultraviolet-B-exposed human epidermis, stem cell factor transcripts
      and protein expression were also markedly enhanced compared with the nonexposed
      epidermis. Immunohistochemistry with antibodies to stem cell factor revealed an
      increased staining in the ultraviolet-B-exposed epidermis, which was accompanied
      by a slight epidermal hyperplasia. In the course of ultraviolet-B-induced
      pigmentation of brownish guinea pig skin, the subepidermal injection of c-kit
      inhibitory antibodies completely abolished the induction of pigmentation in the
      ultraviolet-B-exposed area, and there was no increase in the number of
      dihydroxyphenylalanine-positive melanocytes. These findings indicate that the
      stem cell factor/c-kit signaling is critically involved in the biologic mechanism
      of ultraviolet-B-induced pigmentation.

PMID- 11286627
TI  - An alternative approach to depigmentation by soybean extracts via inhibition of
      the PAR-2 pathway.
AB  - The protease-activated receptor 2, expressed on keratinocytes but not on
      melanocytes, has been ascribed functional importance in the regulation of
      pigmentation by phagocytosis of melanosomes. Inhibition of protease-activated
      receptor 2 activation by synthetic serine protease inhibitors requires
      keratinocyte-melanocyte contact and results in depigmentation of the dark skinned
      Yucatan swine, suggesting a new class of depigmenting mechanism and agents. We
      therefore examined natural agents that could exert their effect via the protease
      activated receptor 2 pathway. Here we show that soymilk and the soybean-derived
      serine protease inhibitors soybean trypsin inhibitor and Bowman-Birk inhibitor
      inhibit protease-activated receptor 2 cleavage, affect cytoskeletal and cell
      surface organization, and reduce keratinocyte phagocytosis. The depigmenting
      activity of these agents and their capability to prevent ultraviolet-induced
      pigmentation are demonstrated both in vitro and in vivo. These results imply that
      inhibition of the protease-activated receptor 2 pathway by soymilk may be used as
      a natural alternative to skin lightening.

PMID- 11286628
TI  - Antagonistic effects of the staphylococcal enterotoxin a mutant, SEA(F47A/D227A),
      on psoriasis in the SCID-hu xenogeneic transplantation model.
AB  - Psoriasis is a T-cell-mediated immune dermatosis probably triggered by bacterial
      superantigens. This pathomechanism has been experimentally reproduced in a SCID
      hu xenogeneic transplantation model. We analyzed the effects of different
      bacterial superantigens on the induction of psoriasis in this model.
      Staphylococcal enterotoxin B and exfoliative toxin triggered the onset of
      psoriasis when administered repetitively intracutaneously over a period of 2 wk,
      whereas staphylococcal enterotoxin A representing a distinct subfamily of
      staphylococcal enterotoxins only mimicked certain aspects of psoriasis. The
      biologic effects of staphylococcal enterotoxin A were more pronounced when a
      mutated form, SEA(H187A), of this superantigen with reduced affinity to major
      histocompatibility complex class II was coinjected. Another mutated variant,
      SEA(F47A/D227A), exhibiting no measurable major histocompatibility complex class
      II affinity blocked the effects triggered by wild-type staphylococcal enterotoxin
      A when injected in a 10-fold higher dose. Inhibition was specific as induction of
      psoriasiform epidermal changes by staphylococcal enterotoxin B could not be
      blocked. As staphylococcal enterotoxin A, in contrast to the other superantigens
      tested, is capable of inducing epidermal thickening but not the typical
      appearance of psoriasis, we conclude that bacterial superantigens may differ with
      regard to their effects on human nonlesional psoriatic skin. Staphylococcal
      enterotoxin-A-mediated effects were blocked by a genetically engineered
      superantigen highlighting the potential therapeutic use of mutated superantigens.

PMID- 11286629
TI  - Adenoviral gene transfer restores lysyl hydroxylase activity in type VI Ehlers
      Danlos syndrome.
AB  - Type VI Ehlers-Danlos syndrome is a disease characterized by disturbed lysine
      hydroxylation of collagen. The disease is caused by mutations in lysyl
      hydroxylase 1 gene and it affects several organs including the cardiovascular
      system, the joint and musculoskeletal system, and the skin. The skin of type VI
      Ehlers-Danlos syndrome patients is hyperelastic, scars easily, and heals slowly
      and poorly. We hypothesized that providing functional lysyl hydroxylase 1 gene to
      the fibroblasts in and around wounds in these patients would improve healing. In
      this study we tested the feasibility of transfer of the lysyl hydroxylase 1 gene
      into fibroblasts derived from rats and a type VI Ehlers-Danlos syndrome patient
      (in vitro) and into rat skin (in vivo). We first cloned human lysyl hydroxylase 1
      cDNA into a recombinant adenoviral vector (Ad5RSV-LH). Transfection of human type
      VI Ehlers-Danlos syndrome fibroblasts (about 20% of normal lysyl hydroxylase 1
      activity) with the vector increased lysyl hydroxylase 1 activity in these cells
      to near or greater levels than that of wild type, unaffected fibroblasts. The
      adenoviral vector successfully transfected rat fibroblasts producing both beta
      galactosidase and lysyl hydroxylase 1 gene activity. We next expanded our studies
      to a rodent model. Intradermal injections of the vector to the abdominal skin of
      rats produced lysyl hydroxylase 1 mRNA and elevated lysyl hydroxylase 1 activity,
      in vivo. These data suggest the feasibility of gene replacement therapy to modify
      skin wound healing in type VI Ehlers-Danlos syndrome patients.

PMID- 11286630
TI  - Novel splice site mutation in keratin 1 underlies mild epidermolytic palmoplantar
      keratoderma in three kindreds.
AB  - We report a novel mutation in the exon 6 splice donor site of keratin 1 (G4134A)
      that segregates with a palmoplantar keratoderma in three kindreds. The nucleotide
      substitution leads to the utilization of a novel in-frame splice site 54 bases
      downstream of the mutation with the subsequent insertion of 18 amino acids into
      the 2B rod domain. This mutation appears to have a milder effect than previously
      described mutations in the helix initiation and termination sequence on the
      function of the rod domain, with regard to filament assembly and stability.
      Affected individuals displayed only mild focal epidermolysis in the spinous layer
      of palmoplantar epidermis, in comparison with cases of bullous congenital
      ichthyosiform erythroderma also due to keratin 1 mutations, which show widespread
      and severe epidermolysis. This study describes a novel mutation in KRT1 that
      results in a phenotype distinct from classical bullous congenital ichthyosiform
      erythroderma.

PMID- 11286631
TI  - Homozygous variegate porphyria: 20 y follow-up and characterization of molecular
      defect.
AB  - The long-term follow-up of a homozygous variegate porphyria patient revealed
      severe photosensitivity accompanied by mild sensory neuropathy and IgA
      nephropathy. A 35T to C transition in exon 2 (I12T) and a 767C to G transversion
      in exon 7 (P256R) of the protoporphyrinogen oxidase gene were identified from
      both alleles of the patient's cDNA and genomic DNA samples. Both prokaryotic and
      eukaryotic expression studies showed that the first mutation in the evolutionary
      conserved region resulted in a decrease in the protoporphyrinogen oxidase
      activity in contrast to the polymorphic substitution in exon 7, which affected
      the function of the enzyme assayed in Escherichia coli but not COS-1 cells.

PMID- 11286632
TI  - PTCH mutations in squamous cell carcinoma of the skin.
AB  - Ultraviolet light exposure is the major risk factor for the development of
      squamous cell carcinoma in Caucasians. Mutations in the tumor suppressor gene p53
      have been identified in both squamous cell carcinomas and basal cell carcinomas.
      The human homolog of the Drosophila patched gene, has been shown to be mutated in
      sporadic basal cell carcinomas; however, mutations in the patched gene have not
      been found in squamous cell carcinoma. In this study, we screened a total of 20
      squamous cell carcinoma samples for mutations in the patched gene. Using
      polymerase chain reaction-single strand conformation polymorphism as an initial
      screening method, we identified one non-sense mutation, two mis-sense mutations
      and three silent mutations in five squamous cell carcinoma samples. In one
      squamous cell carcinoma sample, we identified a tandem GG-->AA transitional
      change at nucleotide 3152 in exon 18 of the patched gene that resulted in a
      premature stop codon at codon 1051. The three squamous cell carcinoma samples
      containing non-sense and mis-sense mutations were isolated from individuals with
      histories of multiple basal cell carcinoma. Sequence analysis of the p53 gene in
      these five squamous cell carcinoma samples identified one CC-->TT and three C-->T
      ultraviolet-specific nucleotide changes. Our study provides evidence that the
      patched gene is mutated in squamous cell carcinoma from individuals with a
      history of multiple basal cell carcinoma. The identification of ultraviolet
      specific nucleotide changes in both tumor suppressor genes supports the notion
      that ultraviolet exposure plays an important part in the development of squamous
      cell carcinoma.

PMID- 11286633
TI  - Contrasting localization of c-Myc with other Myc superfamily transcription
      factors in the human hair follicle and during the hair growth cycle.
AB  - The mammalian hair follicle is a highly dynamic skin appendage that undergoes
      repeated cycles of growth and regression, involving closely co-ordinated
      regulation of cell proliferation, differentiation, and apoptosis. The Myc
      superfamily of transcription factors have been strongly implicated in the
      regulation of these processes in many tissues. Using immunohistochemistry, we
      have investigated the patterns of c-Myc, N-Myc, Max, and Mad1-4 expression at
      different stages of the human hair growth cycle. N-Myc, Max, Mad1, and Mad3
      immunoreactivity was detected in the epidermis and the epithelium of both anagen
      and telogen hair follicles. Three distinct patterns of hair follicle c-Myc
      immunoreactivity were observed. In the infundibulum, c-Myc staining was
      predominantly in the basal layers, with little detectable immunoreactivity in the
      terminally differentiating suprabasal layers; this pattern was similar to that
      seen in the epidermis. In contrast, c-Myc expression in the follicle bulb was
      found both in the proliferating germinative epithelial cells and in the
      terminally differentiating matrix cells that give rise to the hair fiber.
      Finally, intense c-Myc immunoreactivity was detected in the bulge region of the
      outer root sheath. Using the C8/144B antibody as a bulge marker, we confirmed
      that c-Myc immunoreactivity in the outer root sheath correlates with the putative
      hair follicle stem cell compartment. c-Myc expression in the bulge was
      independent of the hair growth cycle stage. Our data suggest that Myc superfamily
      members serve different functions in separate epithelial compartments of the hair
      follicle and may play an important role in determining cell fate within the
      putative stem cell compartment.

PMID- 11286634
TI  - Fibroblast growth factor 10 induces proliferation and differentiation of human
      primary cultured keratinocytes.
AB  - Fibroblast growth factor 10 is a novel member of the fibroblast growth factor
      family, which is involved in morphogenesis and epithelial proliferation. It is
      highly homologous to the keratinocyte growth factor (or fibroblast growth factor
      7), a key mediator of keratinocyte growth and differentiation. Both fibroblast
      growth factor 10 and keratinocyte growth factor bind with high affinity to the
      tyrosine kinase keratinocyte growth factor receptor. Here we analyzed the effect
      of fibroblast growth factor 10 on primary cultures of human keratinocytes, grown
      in chemically defined medium, and we compared the proliferative and
      differentiative cell responses to fibroblast growth factor 10 with those induced
      by keratinocyte growth factor and epidermal growth factor. Cell counting, 5-bromo
      2'-deoxyuridine incorporation, and western blot analysis showed that fibroblast
      growth factor 10, similarly to keratinocyte growth factor, not only is a potent
      mitogen for human keratinocytes, but also promotes the expression of both early
      differentiation markers K1 and K10 and late differentiation marker filaggrin in
      response to the Ca2+ signal, and seems to sustain the proliferative activity in
      suprabasal stratified cells. Immunoprecipitation/western blot analysis revealed
      that fibroblast growth factor 10, similarly to keratinocyte growth factor, is
      able to induce tyrosine phosphorylation of keratinocyte growth factor receptor
      and of cellular substrates such as PLCgamma.

PMID- 11286635
TI  - Selective femtosecond pulse-excitation of melanin fluorescence in tissue.

PMID- 11286636
TI  - CTLA4 gene polymorphisms are associated with, and linked to, insulin-dependent
      diabetes mellitus in a Russian population.
AB  - BACKGROUND: The association between the human cytotoxic T lymphocyte-associated
      antigen-4 (CTLA4) gene and insulin-dependent diabetes mellitus (IDDM) is unclear
      in populations. We therefore investigated whether the gene conferred
      susceptibility to IDDM in a Russian population. We studied two polymorphic
      regions of the CTLA4 gene, the codon 17 dimorphism and the (AT)n microsatellite
      marker in the 3' untranslated region in 56 discordant sibling pairs and in 33
      identical by descent (IBD) affected sibships. RESULTS: The Alal7 allele of the
      CTLA4 gene was preferentially transmitted from parents to diabetic offspring
      (p<0.0001) as shown by the combined transmission/disequlibrium test (TDT) and sib
      TDT (S-TDT) analysis. A significant difference between diabetic and non-diabetic
      offspring was also observed for the transmission of alleles 17, 20, and 26 of the
      dinucleotide microsatellite. Allele 17 was transmitted significantly more
      frequently to affected offspring than to other children (p=0.0112) whereas
      alleles 20 and 26 were transmitted preferentially to non-diabetic sibs (p=0.045
      and 0.00068 respectively). A nonrandom excess of the Ala17 CTLA4 molecular
      variant (maximum logarithm of odds score (MLS) of 3.26) and allele 17 of the
      dinucleotide marker (MLS=3.14) was observed in IBD-affected sibling pairs.
      CONCLUSION: The CTLA4 gene is strongly associated with, and linked to IDDM in a
      Russian population.

PMID- 11286637
TI  - Search for antisense copies of beta-globin mRNA in anemic mouse spleen.
AB  - BACKGROUND: Previous studies by Volloch and coworkers have reported that during
      the expression of high levels of beta-globin mRNA in the spleen of anemic mice,
      they could also detect small but significant levels of an antisense (AS) globin
      RNA species, which they postulated might have somehow arisen by RNA-directed RNA
      synthesis. For two reasons we undertook to confirm and possibly extend these
      studies. First, previous studies in our lab have focussed on what is an
      unequivocal example of host RNA-directed RNA polymerase activity on the RNA
      genome of human hepatitis delta virus. Second, if AS globin species do exist they
      could in turn form double-stranded RNA species which might induce post
      transcriptional gene silencing, a phenomenon somehow provoked in eukaryotic cells
      by AS RNA sequences. RESULTS: We reexamined critical aspects of the previous
      globin studies. We used intraperitoneal injections of phenylhydrazine to induce
      anemia in mice, as demonstrated by the appearance and ultimate disappearance of
      splenomegaly. While a 30-fold increase in globin mRNA was detected in the spleen,
      the relative amount of putative AS RNA could be no more than 0.004%. CONCLUSIONS:
      Contrary to earlier reports, induction of a major increase in globin transcripts
      in the mouse spleen was not associated with a detectable level of antisense RNA
      to globin mRNA.

PMID- 11286638
TI  - Role of nitrogen oxides on eicosanoid production during atherosclerosis:
      understanding the controversies.

PMID- 11286639
TI  - Evidence for expanded clinical utility of statin drugs.

PMID- 11286640
TI  - Genetic determinants of plasma triglycerides: impact of rare and common
      mutations.
AB  - Raised plasma triglyceride (TG) levels are an independent risk factor for
      coronary artery disease (CAD), and thus understanding the genetic and
      environmental determinants of TG levels are of major importance. TG metabolism is
      a process for delivering free fatty acids for energy storage or b-oxidation, and
      involves a number of different hydrolytic enzymes and apolipoproteins (apo). The
      genes encoding these proteins are, therefore, candidates for determining plasma
      TGs. Although rare mutations in lipoprotein lipase (LPL), the major TG
      hydrolyzing enzyme, and apo CII (APOC2), its essential activator, result in
      extremely high plasma TG levels, their low frequency means they have little
      impact upon TG levels in the general population. Common mutations in LPL, apo
      CIII (APOC3), and apo E (APOE) have the strongest effect on plasma TG levels at
      the population level. In addition, environmental factors such as diet, obesity,
      and smoking interact with genetic determinants of TG to produce a modulating high
      risk environment.

PMID- 11286641
TI  - Gene-diet interaction and plasma lipid response to dietary intervention.
AB  - Research in the field of gene-diet interactions as determinants of plasma lipid
      response to dietary interventions has accumulated a substantial body of evidence
      during the past decade. Several candidate genes have shown some promise as
      potential markers of individual dietary responsiveness. Among the best
      characterized are the APOE, APOA4, APOB, APOC3, and LPL loci. Other genes are
      being continuously incorporated to this most interesting search. However, in very
      few cases has consensus been achieved about the usefulness of genetic markers as
      clinically significant predictors of dietary response. The increased ability to
      generate genotypic information, in combination with the knowledge from the human
      genome project and more comprehensive experimental designs, will dramatically
      improve our capacity to answer many of our current questions. It will also help
      to prove that knowledge of an individual's genetic background will facilitate
      more precise dietary counseling and intervention, and more efficacious primary
      and secondary coronary heart disease prevention.

PMID- 11286642
TI  - The genetics of venous and arterial thromboembolism.
AB  - There is substantial evidence to indicate that the pathologic processes of venous
      and arterial thromboembolism involve both genetic and environmental influences.
      Scientific progress over the past decade has revealed a growing number of genetic
      factors, such as factor V Leiden and the prothrombin gene variant, that are
      present in more than 1% of the population and increase the relative risk of
      venous thrombosis between two- and sevenfold. Furthermore, several of these
      factors have been demonstrated to interact adversely with environmental
      influences, such as oral contraceptives and smoking. Although these traits are
      present at relatively high prevalence in the population, the magnitude of the
      increased thrombotic risk associated with these factors is substantially less
      than that related to inherited deficiency of the natural anticoagulant protein
      antithrombin, and somewhat less than the elevated risk with protein C and protein
      S deficiencies. In contrast to the progress that has been made in understanding
      the genetic contributions to venous thromboembolism, much still remains to be
      learned about the genetic basis of arterial thrombosis. Despite the documentation
      of associations between several genetic polymorphisms with plasma procoagulant
      levels, consistent associations with arterial thrombotic disease have not been
      found.

PMID- 11286643
TI  - Genes and environment in type 2 diabetes and atherosclerosis in aboriginal
      Canadians.
AB  - The incidence of coronary heart disease (CHD) among aboriginal people in northern
      Ontario has tripled over the past 20 years. This is inextricably linked to the
      remarkably high prevalence of type 2 diabetes in these native communities.
      Approximately 40% of the Oji-Cree of northern Ontario have typical obesity
      related type 2 diabetes, which represents a drastic increase from virtually
      unreportable levels 50 years ago. The Oji-Cree have a private mutation in the
      HNF1A gene, namely G319S, which is absent from other ethnic groups and aboriginal
      populations. The most compelling reasons that HNF1A S319 is a diabetes
      susceptibility allele are its consistent statistical association with the
      presence and severity of diabetes. Also, HNF1A S319 has specificity and positive
      predictive values of 97% and 95%, respectively, for the development of diabetes
      in the Oji-Cree by 50 years of age. This makes the HNF1A G319S genotype the most
      specific predictive genetic test for diabetes in any human population. HNF1A S319
      has all the attributes of a thrifty allele in the Oji-Cree. It is possible that
      the recent increase in CHD in the aboriginal people of northern Ontario is the
      result of the expression of diabetes susceptibility due to HNF1A S319 as a
      consequence of rapid changes in environment and lifestyle.

PMID- 11286644
TI  - Plaque angiogenesis and atherosclerosis.
AB  - Therapeutic angiogenesis trials refer to the stimulation of collateral arterioles
      and new vascular conduits to perfuse ischemic myocardium and limbs.
      Atherosclerotic lesions responsible for vascular occlusions themselves are
      associated with angiogenesis within the vessel wall. Plaque neovascularization is
      comprised of a network of capillaries that arise from the adventitial vasa
      vasorum and extend into the intimal layer of atherosclerotic lesions and other
      types of vascular injury. The functions of these plaque capillaries are proposed
      to be important regulators of plaque growth and lesion instability. The
      development of agents that are positive and negative regulators of angiogenesis
      may have potential therapeutic implications in the progression and acute
      manifestations of atherosclerosis. This review focuses on the role of plaque
      angiogenesis in atherosclerosis and discusses the potential therapeutic
      applications of angiogenesis inhibitors in this disease.

PMID- 11286645
TI  - Biologic effect and molecular regulation of vascular apoptosis in
      atherosclerosis.
AB  - Apoptosis, a form of genetically programmed cell death, plays a key role in
      regulation of cellularity of the arterial wall. During atherogenesis, deregulated
      apoptosis may cause abnormalities of arterial morphogenesis, wall structural
      stability, and metabolisms. Many biophysiologic and biochemical factors,
      including mechanical forces, reactive oxygen and nitrogen species, cytokines,
      growth factors, oxidized lipoproteins, etc. may influence apoptosis of vascular
      cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein
      family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc
      may be activated in atherosclerotic lesions and mediate vascular apoptosis during
      the development of atherosclerosis. Abnormal expression and dysfunction of these
      apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis
      and affect the integrity and stability of plaques. Clarification of the molecular
      mechanism that regulates apoptosis may help design a new strategy for treatment
      of atherosclerosis and its major complication, the acute vascular syndromes.

PMID- 11286646
TI  - The role of chemokines in atherosclerosis.
AB  - Recruitment of mononuclear leukocytes and the migration, growth, and activation
      of the multiple cell types within atherosclerotic lesions are critical features
      of the chronic inflammatory and fibroproliferative response central to
      atherosclerosis. Attraction of leukocyte to tissues is controlled by chemokines,
      whose presence is well documented in atherosclerotic lesions. Studies using
      knockout and transgenic murine models have demonstrated that chemokine
      receptor/ligand interactions are of crucial importance in the development of
      atherosclerosis. Beyond their chemotactic effect on mononuclear leukocytes,
      chemokines may also interfere with smooth muscle cell migration and growth, as
      well as platelet activation and other well-defined features of the
      atherosclerotic process. There is no doubt that the identification of chemokines
      as important vascular signals has provided insights into our understanding of
      basic cellular and molecular mechanism of atherosclerosis. Thus, there is
      evidence that chemokine receptor/ligands could be identified as potential new
      targets for therapeutic intervention to prevent or control atherosclerosis in the
      near future.

PMID- 11286647
TI  - Atherogenesis and the arginine hypothesis.
AB  - In patients who have elevated levels of plasma ADMA, a relative deficiency of L
      arginine has been found to contribute to the pathophysiology of athersclerosis,
      causing vasoconstriction, and accelerating atherogenesis. This finding--that
      there is a relative deficiency of L-arginine in atherosclerotic disease--is a
      breakthrough that will open new avenues of therapy.

PMID- 11286649
TI  - Risk-taking in the Era of Highly Active Antiretroviral Therapy.

PMID- 11286648
TI  - What has intravascular ultrasound taught us about plaque biology?
AB  - Intravascular ultrasound (IVUS) has a defined role in the cardiac catheterization
      laboratory to assess lesion severity and the procedural success of vascular
      interventions. However, IVUS has also contributed to our understanding of the
      biology of atherosclerosis and restenosis. In acute coronary syndromes, IVUS has
      revealed varying degrees of stenosis, thrombosis, and plaque derangement typical
      of the plaque disruption seen in many pathologic studies of patients who have
      died of this condition. IVUS has demonstrated that the culprit lesions of
      patients surviving acute coronary syndromes also tend to be softer, with less
      calcium, and tend to have more plaque with positive arterial remodeling
      (compensatory enlargement) than lesions causing stable coronary syndromes.
      Arterial remodeling is also an important component of restenosis after coronary
      interventions. IVUS has suggested that interventions that reduce restenosis tend
      to have a greater impact on preventing negative remodeling (constriction) rather
      than reducing neointimal proliferation. Oxidant stress may be an important
      contributor to negative remodeling, as IVUS has demonstrated this anatomy at
      sites of coronary artery spasm. Positive remodeling seen by IVUS is also
      associated with impaired endothelial vasomotor dysfunction, and IVUS studies have
      demonstrated the contribution of vasomotor tone to arterial elasticity. Future
      directions include integrating IVUS with other imaging modalities, such as
      angiography, to study the interaction of anatomic and physiologic factors in
      atherosclerosis progression, and using the raw ultrasound signal to distinguish
      plaque components and differences in wall strain that may identify vulnerable
      plaques.

PMID- 11286650
TI  - Management and Prevention of Clostridium difficile-Associated Diarrhea.
AB  - Clostridium difficile is a major cause of antibiotic-associated diarrhea. While
      treatment regimens for C. difficile have been available for decades, they remain
      less than optimal due to the frequent recurrences that occur after therapy is
      completed. Moreover, the morbidity and expense associated with C. difficile have
      underscored the need for more effective preventive measures than are currently
      available. In this review, we outline the current recommendations for treatment
      and prevention of C. difficile infection and, highlight some promising new
      approaches that may help to control this common nosocomial pathogen in the
      future.

PMID- 11286651
TI  - Campylobacter Enteritis and the Guillain-Barre Syndrome.
AB  - Campylobacter jejuni is one of the most common causes of bacterial
      gastroenteritis in the United States and worldwide with approximately 2.4 million
      infections per year in the United States. A now clearly recognized sequelae
      following Campylobacter infection is the Guillain-Barre syndrome, an acute immune
      mediated attack on the peripheral nervous system. How Campylobacter induces
      Guillain-Barre syndrome is the subject of intense investigation, and this article
      discusses some of the recent advances in our understanding of the clinical,
      epidemiologic, and pathogenic features of the disease.

PMID- 11286652
TI  - Recent Advances in the Management of Infections in Liver Transplant Recipients.
AB  - Antimicrobial-resistant bacteria (vancomycin-resistant enterococci and
      Staphylococcus aureus) have emerged as leading pathogens in liver transplant
      recipients. Liver transplant recipients have also been shown to be uniquely more
      susceptible to harboring extended-spectrum beta-lactamase-producing
      Enterobacteriaceae. The frequency of mycelial fungal infections has increased;
      however, effective prophylaxis and management of these infections remains
      suboptimal. Emerging reports have highlighted the morbidity due to novel
      herpesviruses in these patients. Finally, the emergence of ganciclovir resistance
      in cytomegalovirus has implications relevant for all solid organ transplant
      recipients.

PMID- 11286653
TI  - Issues in HIV/Hepatitis C Co-infection.
AB  - Co-infection of patients with hepatitis C virus (HCV) and HIV is prevalent. HCV
      disease is clearly exacerbated in the setting of HIV disease, and the long-term
      effects of HCV have become an increasing concern as patients live longer on
      highly active antiretroviral therapy. Although treatment for HCV disease is
      evolving rapidly, its role in the HIV-infected patient is not well delineated.
      This review will focus on the major issues in the HIV/HCV co-infected patient and
      discuss therapy for HCV in the era of highly active antiretroviral therapy.

PMID- 11286655
TI  - Clinical Trials Report.

PMID- 11286654
TI  - Current Options for the Therapy of Chronic Hepatitis B Infection.
AB  - Until recently the only available treatment for chronic hepatitis B was
      interferon-alpha. Over the past few years a new class of antiviral has become
      available, the reverse transcriptase inhibitors. Lamivudine is a nucleoside
      analogue reverse transcriptase inhibitor that was recently approved in many
      countries for the treatment of hepatitis B. Despite the potent action of
      lamivudine, the development of new antivirals and new strategies to treat
      hepatitis B are still the major goal. We review the latest options for therapy of
      chronic hepatitis B, including combination strategies that could be an approach
      to improving the response rate of antivirals.

PMID- 11286656
TI  - Impact of New Sexually Transmitted Disease Diagnostics on Clinical Practice and
      Public Health Policy.
AB  - Nucleic acid amplification tests (NAAT) offer enhanced sensitivity and excellent
      specificity for many sexually transmitted diseases. For some pathogens for which
      a practical diagnostic test does not exist, such as human papillomavirus (HPV),
      NAAT are also useful. Further, most NAAT can be applied to less "invasive"
      patient specimens, including urine and vaginal fluid. This dramatically increases
      opportunities to test persons outside of traditional clinic settings. Use of NAAT
      has resulted in revisions of the proportion of sexually transmitted diseases
      (STDs) that are asymptomatic, and has increased measured prevalence of some STDs,
      notably Chlamydia trachomatis. NAAT have helped to clarify the eitiologies of
      genital ulcer disease and urethritis, and have provided a more complete picture
      of the natural history of genital herpes and HPV. The ability of polymerase chain
      reaction to detect HPV may change the management of patients who have abnormal
      Pap smears. Efforts to bear the relatively high cost of NAAT, such as pooling
      urine, are under study. NAAT for bacterial STD should be in populations at high
      risk for asymptomatic STD, especially those who might not access routine STD
      screening at traditional settings. Working through the cost to health care
      systems, including the public health arena, and implementation at the laboratory
      level are challenges to overcome before NAAT become the standard of care in most
      settings.

PMID- 11286657
TI  - Role of Vaginal Flora As a Barrier to HIV Acquisition.
AB  - Recent evidence has linked bacterial vaginosis with acquisition of sexually
      transmitted diseases, including HIV infection. Prospective data show that women
      with bacterial vaginosis are at a significantly higher risk for HIV infection
      than those without bacterial vaginosis. The hallmark of bacterial vaginosis is
      the shift in the microbiology of the vaginal flora away from a lactobacilli
      predominant milieu. In particular, lactobacilli that produce hydrogen peroxide
      are notably absent. Hydrogen peroxide-producing lactobacilli have been shown in
      vitro to be virucidal to HIV. Thus, the lack of these apparently protective
      bacteria, along with other local changes resulting from the shift in microflora,
      is thought to represent a biological risk factor for HIV acquisition.

PMID- 11286658
TI  - Quinolone Resistance in Neisseria gonorrhoeae.
AB  - Single-dose oral quinolones have been recommended for gonorrhea treatment since
      1989. The antimicrobial resistance surveillance system has detected several
      outbreaks of quinolone-resistant gonococcal infections (QRNG), and sporadic
      treatment failures have been reported from high-incidence areas such as southeast
      Asia. QRNG may result from mutations that cause structural-functional changes in
      DNA topoisomerase (the quinolone target enzyme) or by changes in antimicrobial
      transport into the bacteria. QRNG has occurred sporadically in the United States,
      predominantly in persons with contact to persons in southeast Asia, and has
      typically occurred as an epiphenomenon in persons who were treated with other
      regimens. Nevertheless, this entity warrants close monitoring. The emergence of
      QRNG is probably related to antimicrobial misuse and overuse, in particular long
      term suppressive or subtherapeutic doses.

PMID- 11286659
TI  - Efforts to Control Sexually Transmitted Diseases As a Means to Limit HIV
      Transmission: Pros and Cons.
AB  - A large body of literature suggests that treatment of sexually transmitted
      diseases (STDs) has a measurable effect on reducing HIV infectiousness and
      susceptibility at both the individual and general population levels. Recent
      research includes biological studies on genital herpes and genital shedding of
      HIV-1; two large-scale, community-based clinical trials in Africa; and the use of
      mathematical modeling to further explore data from these landmark trials. These
      studies suggest that a combination of improved STD services, syndromic
      management, and periodic mass treatment tailored to the dynamics of the
      HIV/AIDS/STD epidemic in a given population can help reduce overall HIV
      transmission.

PMID- 11286660
TI  - Will New Human Papillomavirus Diagnostics Improve Cervical Cancer Control
      Efforts?
AB  - With the causal link between specific types of human papillomavirus (HPV) and
      cervical cancer firmly established, efforts have turned to assessing the relative
      merits of offering HPV testing in screening, triage, and posttreatment
      management. Many unanswered questions remain, but a growing body of evidence
      supports a role for HPV testing in cervical cancer prevention programs. Already,
      clinical centers that serve thousands of women in Europe and the United States
      have incorporated HPV DNA tests in triage algorithms.

PMID- 11286661
TI  - Metabolic Complications of HIV and AIDS.
AB  - Nutritional problems in the patient with HIV/AIDS may include both wasting and
      the more recently described lipodystrophy syndromes, which are complex disorders
      of body composition and metabolism associated with antiretroviral therapy. In
      this paper we review the pathophysiology and treatment options for both wasting
      and lipodystrophy.

PMID- 11286662
TI  - New Drugs for the Treatment of HIV Infection.
AB  - Despite the availability of 15 approved drugs for the treatment of HIV infection,
      issues of convenience, tolerability, and antiretroviral activity make the
      continued development of newer drugs important. New drugs in clinical development
      represent both existing classes of antiretroviral agents--reverse transcriptase
      inhibitors (eg, diaminopurine dioxolane), nonnucleoside reverse transcriptase
      inhibitors (eg, capravirine), and protease inhibitors (eg, tipranavir and BMS
      232632)--and newer classes of antiretroviral agents, such as nucleotide analogue
      reverse transcriptase inhibitors (eg, tenofovir) and fusion inhibitors (eg,
      pentafuside). Newer drugs may offer improvements over existing agents by having
      simpler dosing schedules (once or twice daily), better tolerability, or improved
      virologic activity against wild-type or resistant virus. Continued advancements
      in HIV treatment will stem from ongoing development of antiretroviral drugs.

PMID- 11286663
TI  - Local medical treatment in rheumatic diseases.

PMID- 11286664
TI  - An update on the science and therapy of obesity and its relationship to
      osteoarthritis.
AB  - Obesity and osteoarthritis are two commonly encountered clinical problems that
      can lead to significant physical and emotional disability. This report examines
      the association between obesity and osteoarthritis, and discusses potential
      mechanisms by which obesity influences osteoarthritis. Special attention is
      devoted to reviewing the molecular and genetic mechanisms that underlie the
      development of clinical obesity. Improved understanding of obesity will hopefully
      lead to improved treatment and subsequent amelioration of this important risk
      factor for osteoarthritis.

PMID- 11286665
TI  - Helicobacter pylori and NSAID gastropathy: an ambiguous association.
AB  - Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are
      associated with adverse gastro- intestinal effects ranging from mild dyspepsia to
      serious complications such as bleeding peptic ulcer. However, controversy
      persists regarding the interaction between these two well-documented risk
      factors. Physiology studies reveal that H. pylori infection can protect the upper
      gastrointestinal tract by increasing prostaglandin levels. In contrast, clinical
      trial evidence suggests that eradication of H. pylori infection leads to a
      decreased risk for endoscopic ulcers in people taking NSAIDs. Given the rates of
      morbidity and mortality and costs attributable to NSAID-associated toxicity,
      preventive strategies to reduce NSAID side-effects remain important. Until
      controlled investigations definitively quantify the effect of H. pylori infection
      and eradication on clinically significant adverse events, a compelling argument
      can be made for H. pylori testing of chronic NSAID users at increased risk for
      ulcer disease and eradicating the organism if present.

PMID- 11286666
TI  - Meta-analysis of antidepressants in fibromyalgia.

PMID- 11286667
TI  - Fibromyalgia and other unexplained clinical conditions.
AB  - Several unexplained clinical conditions frequently coexist with fibromyalgia;
      these include chronic fatigue syndrome, irritable bowel syndrome,
      temporomandibular disorder, tension and migraine headaches, and others. However,
      only recently have studies directly compared the physiological parameters of
      these conditions (eg, fibromyalgia vs irritable bowel syndrome) to elucidate
      underlying pathogenic mechanisms. This review summarizes data from comparative
      studies and discusses their implications for future research.

PMID- 11286668
TI  - Cognitive dysfunction in fibromyalgia.
AB  - Fibromyalgia is a puzzling syndrome of widespread musculoskeletal pain. In
      addition to pain, patients with fibromyalgia frequently report that cognitive
      function, memory, and mental alertness have declined. A small body of literature
      suggests that there is cognitive dysfunction in fibromyalgia. This article
      addresses several questions that physicians may have regarding cognitive function
      in their patients. These questions concern the types of cognitive tasks that are
      problematic for patients with fibromyalgia, the role of psychological factors
      such as depression and anxiety, the role of physical factors such as pain and
      fatigue, the nature of patients' perceptions of their cognitive abilities, and
      whether patients can be tested for cognitive dysfunction. Critical areas for
      further investigation are highlighted.

PMID- 11286669
TI  - The role of gender in fibromyalgia syndrome.
AB  - Fibromyalgia syndrome (FMS), characterized by widespread pain and tenderness on
      palpation (tender points), is much more common in women than in men in a
      proportion of 9:1. Two recent studies have shown important gender differences in
      various clinical characteristics of FMS. In a community and a clinic sample,
      women experienced significantly more common fatigue, morning fatigue, hurt all
      over, total number of symptoms, and irritable bowel syndrome. Women had
      significantly more tender points. Pain severity, global severity and physical
      functioning were not significantly different between the sexes, nor were
      psychologic factors, eg, anxiety, stress, and depression. Gender differences have
      also been observed in other related syndromes, eg, chronic fatigue syndrome,
      irritable bowel syndrome, and headaches. The mechanisms of gender differences in
      these illnesses are not fully understood, but are likely to involve an
      interaction between biology, psychology, and sociocultural factors.

PMID- 11286670
TI  - Exercise for patients with fibromyalgia: risks versus benefits.
AB  - Although exercise in the form of stretching, strength maintenance, and aerobic
      conditioning is generally considered beneficial to patients with fibromyalgia
      (FM), there is no reliable evidence to explain why exercise should help alleviate
      the primary symptom of FM, namely pain. Study results are varied and do not
      provide a uniform consensus that exercise is beneficial or what type, intensity,
      or duration of exercise is best. Patients who suffer from exercise-induced pain
      often do not follow through with recommendations. Evidence-based prescriptions
      are usually inadequate because most are based on methods designed for persons
      without FM and, therefore, lack individualization. A mismatch between exercise
      intensity and level of conditioning may trigger a classic neuroendocrine stress
      reaction. This review considers the adverse and beneficial effects of exercise.
      It also provides a patient guide to exercise that takes into account the risks
      and benefits of exercise for persons with FM.

PMID- 11286671
TI  - Complementary and alternative therapies for fibromyalgia.
AB  - Fibromyalgia (FM) is a syndrome of chronic widespread musculoskeletal pain that
      is accompanied by sleep disturbance and fatigue. Clinical treatment usually
      includes lifestyle modifications and pharmacologic interventions meant to relieve
      pain, improve sleep quality, and treat mood disorders. These therapies are often
      ineffective or have been shown in clinical studies to have only short-term
      effectiveness. Pharmacologic treatments have considerable side effects. Patients
      may have difficulty complying with exercise-based treatments. Thus, patients seek
      alternative therapeutic approaches and physicians are routinely asked for advice
      about these treatments. This article reviews nontraditional treatment
      alternatives, from use of nutritional and herbal supplements to acupuncture and
      mind-body therapy. Little is known about efficacy and tolerance of complementary
      and alternative therapies in FM and other chronic musculoskeletal pain syndromes.
      Most studies on these treatments have been performed for osteoarthritis,
      rheumatoid arthritis, or focal musculoskeletal conditions. Clinical trials are
      scarce; the quality of these trials is often criticized because of small study
      population size, lack of appropriate control interventions, poor compliance, or
      short duration of follow-up. However, because of widespread and growing use of
      alternative medicine, especially by persons with chronic illnesses, it is
      essential to review efficacy and adverse effects of complementary and alternative
      therapies.

PMID- 11286672
TI  - The role of psychiatric disorders in fibromyalgia.
AB  - The cardinal features of fibromyalgia are chronic widespread pain in the presence
      of widespread tenderness as measured by multiple tender points. Despite extensive
      investigations, the etiology of this syndrome remains unclear. Increased rates of
      psychiatric disorders, particularly depressive, anxiety, and somatoform
      disorders, are apparent in clinic populations. Epidemiologic evidence suggests
      that this is also true for community subjects. Depression, generalized
      psychological distress, and other psychological factors have been shown to be
      associated with the onset and persistence of fibromyalgia symptoms. However, the
      bodily processes through which such factors may lead to the onset of fibromyalgia
      are unclear. Recent investigations have demonstrated altered stress system
      responsiveness, most notably the hypothalamic-pituitary-adrenal stress axis, in
      patients with fibromyalgia. These findings, and one promising avenue for
      investigating the interaction between psychological and biological factors in the
      onset of chronic pain syndromes including fibromyalgia, are discussed.

PMID- 11286673
TI  - Juvenile primary fibromyalgia syndrome.
AB  - Juvenile primary fibromyalgia syndrome (JPFS) is a common musculoskeletal pain
      syndrome of unknown etiology characterized by widespread persistent pain, sleep
      disturbance, fatigue, and the presence of multiple discrete tender points on
      physical examination. Other associated symptoms include chronic anxiety or
      tension, chronic headaches, subjective soft tissue swelling, and pain modulated
      by physical activity, weather, and anxiety or stress. Research and clinical
      observations suggest that JPFS may have a chronic course that impacts the
      functional status and psychosocial development of children and adolescents. In
      addition, several factors have been implicated in the etiology and maintenance of
      JPFS including genetic and anatomic factors, disordered sleep, psychological
      distress, and familial and environmental influences. A multidisciplinary approach
      to treatment of JPFS is advocated, including pharmacologic and nonpharmacologic
      interventions (eg, psychotherapy, aerobic exercise, sleep hygiene).

PMID- 11286675
TI  - Nervous immunity: neurotransmitters, extracellular K+ and T-cell function.
AB  - T cells are required to respond quickly to tissue injuries and dysregulations of
      varied complexity, and do so not under the direction of specific 'classical'
      immunological signals. This suggests that additional signals might be supplied by
      the nervous system and by physiological modulation of the ionic environment to
      activate T cells in a T-cell receptor independent manner.

PMID- 11286676
TI  - Creating therapeutic cancer vaccines: notes from the battlefield.
AB  - With the identification of tumor antigens and a knowledge of how to vaccinate
      against them, the field of tumor immunology faces new challenges. In this
      article, the authors argue that successful immunotherapies of the future will
      activate anti-tumor T cells without inducing their anergy or apoptotic death.

PMID- 11286677
TI  - Signaling from the brink of danger.

PMID- 11286678
TI  - Immature human dendritic cells induce regulatory T cells in vitro.

PMID- 11286679
TI  - A matter of choice....

PMID- 11286680
TI  - A role for the proteasome in HIV infection.

PMID- 11286681
TI  - New drug delivery system developed to prevent immune activation.

PMID- 11286682
TI  - Scientists finally develop transgenic Burkitt's mice.

PMID- 11286683
TI  - RANTES polymorphism affects susceptibility to HIV and asthma.

PMID- 11286684
TI  - Anti B cell therapy proves successful in severe cases of rheumatoid arthritis.

PMID- 11286685
TI  - Measles outbreaks on the horizon?

PMID- 11286686
TI  - Itk/Emt: a link between T cell antigen receptor-mediated Ca2+ events and
      cytoskeletal reorganization.
AB  - Itk/Emt, a tec family tyrosine kinase, is important for T-cell development and
      activation through the antigen receptor. Here, we review data suggesting that
      Itk/Emt is involved in the generation of critical second messengers (Ca(2+), PKC)
      whose duration it modulates by regulation of cytoskeletal reorganization. We
      propose that Itk/Emt constitutes an important link between these critical
      signaling events.

PMID- 11286687
TI  - Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to
      die, that is the mucosal question.
AB  - T-cell resistance against apoptosis contributes to inappropriate T-cell
      accumulation and the perpetuation of chronic mucosal inflammation in inflammatory
      bowel diseases (IBDs). Anti-interleukin-12 (IL-12) and anti-IL-6 receptor
      antibodies suppress colitis activity by the induction of T-cell apoptosis. These
      findings have important implications for the design of effective treatment
      regimens in IBD.

PMID- 11286688
TI  - Mechanism of anti-D-mediated immune suppression--a paradox awaiting resolution?
AB  - During pregnancy, women can be immunized by fetal red blood cells (RBCs) of an
      incompatible blood group. Subsequent transplacental passage of the antibodies can
      result in fetal morbidity or mortality due to RBC destruction. The administration
      of anti-D antibodies to D(-) women after delivery of a D(+) infant, and
      subsequent prevention of Rhesus (Rh) D haemolytic disease of the fetus and
      newborn, is the most successful clinical use of antibody-mediated immune
      suppression. The passive IgG anti-D might prevent immunization to D(+) RBCs by an
      IgG Fcgamma receptor (Fcgamma R)-dependent mechanism such as crosslinking the D
      specific B-cell receptor and inhibitory FcgammaRIIb. However, recent murine
      studies demonstrate that the suppressive effects of antibodies to heterologous
      RBCs can be Fcgamma R-independent, suggesting other mechanisms might contribute.

PMID- 11286689
TI  - Caspases: more than just killers?
AB  - Proteases of the caspase family constitute the central executioners of apoptosis.
      Several recent observations suggest that caspases and apoptosis-regulatory
      molecules exert important functions beyond that of cell death, including the
      control of T-cell proliferation and cell-cycle progression. Here, Los and
      colleagues propose a model that directly connects cell suicide mechanisms to the
      regulation of cell-cycle progression.

PMID- 11286690
TI  - Gene expression physiology and pathophysiology of the immune system.
AB  - Genomic-scale gene expression profiling can reveal cellular physiology with
      unprecedented richness. This technology is being used to define the gene
      expression targets of individual regulatory proteins and signaling pathways.
      Comprehensive databases of gene expression measurements can be used to understand
      the pathological mechanisms underlying disease processes.

PMID- 11286691
TI  - Modulating the immune response with dendritic cells and their growth factors.
AB  - Different subsets of dendritic cells (DCs) appear to play a role in determining
      the specific cytokines secreted by T helper (Th) cells. A model is proposed that
      links together factors such as the pathogen, microenvironment, DCs and T cells in
      a mechanism that results in a flexible determination of T-cell polarization.

PMID- 11286692
TI  - The contribution of proteinase inhibitors to immune defense.
AB  - The colonization of a potential host by a parasite requires an ability to cross
      the integuments and then to escape from the host immune defenses. Proteinases are
      important virulence factors that assist these processes. Host proteinase
      inhibitors potentially contribute to immunity by inactivating the proteinase
      virulence factors of pathogens.

PMID- 11286693
TI  - Divergent and convergent evolution of NK-cell receptors.
AB  - Natural killer (NK)-cell receptors specific for major histocompatibility complex
      (MHC) class I molecules have been identified in humans and mice. Some of the most
      important receptors are structurally unrelated in the two species: the murine Ly
      49 receptors are C-type lectins, while human killer-cell inhibitory receptors
      (KIRs) belong to the immunoglobulin superfamily. Here, Roland Barten and
      colleagues describe the divergent and convergent evolution of NK-cell receptors.

PMID- 11286694
TI  - The role of TALL-1 and APRIL in immune regulation.

PMID- 11286695
TI  - Primitive Toll signalling: bugs, flies, worms and man.

PMID- 11286696
TI  - Complex layers of genetic alteration in the generation of antibody diversity.

PMID- 11286697
TI  - RasGRP: the missing link for Ras activation in thymocytes.

PMID- 11286698
TI  - Double break-point in the match for the mutator.

PMID- 11286699
TI  - Specificity in the innate response: pathogen recognition by Toll-like receptor
      combinations.

PMID- 11286706
TI  - Role of CD30+ T cells in rheumatoid arthritis: a counter-regulatory paradigm for
      Th1-driven diseases.
AB  - CD30 has been proposed to identify Th0/2-type clones. However, the in vivo
      relevance of this finding is still a matter of debate, as high serum levels of
      soluble CD30 have been found in both Th1- and Th2- dominated disorders. Among
      these, rheumatoid arthritis represents a condition where the Th1 predominance is
      combined with the presence of CD30(+) T-cell activity, particularly in specific
      stages of the disease. This article discusses the hypothesis that CD30(+) T cells
      might play a counter-regulatory role at sites of inflammation in Th1-mediated
      conditions, such as rheumatoid arthritis.

PMID- 11286707
TI  - Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice.
AB  - Based on recent findings in myeloid differentiation factor 88 (MyD88)- and Toll
      like receptor (TLR)-knockout mice, Tsuneyasu Kaisho and Shizuo Akira discuss the
      roles of TLRs and MyD88 in dendritic cell (DC) maturation and cytokine
      production. Lipopolysaccharide binds TLR4 and can induce DC maturation in the
      absence of MyD88, whereas CpG DNA binds TLR9 and induces DC maturation in a MyD88
      dependent manner.

PMID- 11286708
TI  - RANTES: a versatile and controversial chemokine.
AB  - The activity of the chemokine RANTES is not restricted merely to chemotaxis. It
      is a powerful leukocyte activator, a feature potentially relevant in a range of
      inflammatory disorders. RANTES has attracted attention because it can potently
      suppress and, in some circumstances, enhance HIV replication. These
      characteristics are critically dependent on its ability to self-aggregate and
      bind to glycosaminoglycans.

PMID- 11286709
TI  - Evolution of bone marrow transplantation--the original immunotherapy.
AB  - Allogeneic bone-marrow transplantation (BMT) has provided a curative treatment
      option for chronic myeloid leukaemia (CML) over the past 20-30 years. New drugs -
      signal transduction inhibitors - that target the bcr-abl oncogene have the
      potential to render such transplantation procedures obsolete and provide hope for
      those without a suitable donor ( approximately 60% of patients). Here, we discuss
      how new drug and immune-based approaches could be combined to enhance treatment
      of this already 'curable' malignancy.

PMID- 11286710
TI  - Structured treatment interruptions to control HIV-1 and limit drug exposure.
AB  - Although therapy-mediated suppression of HIV-1 is effective and results in a
      degree of immune reconstitution, the complications resulting from life-long
      treatment emphasize the need for alternatives. This review discusses the use of
      structured interruptions in antiviral therapy to induce drug-free periods of
      immune-mediated control of HIV-1. Such an approach has the ultimate objective of
      harnessing anti-viral immune responses, reducing drug exposure (toxicity and
      cost) and potentially extending the clinical benefits of a suppressive treatment
      regimen.

PMID- 11286711
TI  - Innate immunity and autoimmunity: from self-protection to self-destruction.
AB  - Innate immune responses provide the body with its first line of defense against
      infections. Signals generated by a subset of lymphocytes, including natural
      killer (NK) cells and natural killer T (NKT) cells, during the early host
      response might have an additional role in determining the nature of downstream
      adaptive immune responses. Here, Fu-Dong Shi, Hans-Gustaf Ljunggren and Nora
      Sarvetnick discuss the role of cellular and soluble components of innate immunity
      in the development of autoimmune diseases. Some putative pathways leading from
      innate immunity to autoimmunity are proposed.

PMID- 11286712
TI  - Viral vectors for dendritic cell-based immunotherapy.
AB  - Transduction of dendritic cells (DCs) by viral vectors genetically engineered to
      express tumor-associated antigens (TAAs) or cytokines can produce a high level of
      transgene expression and is an attractive approach for DC-based immunotherapy. Ex
      vivo transduction allows the control of DC quality, antigen quantity and site of
      DC reinjection. This review evaluates the viral vectors currently being developed
      for use in DC-based immunotherapy.

PMID- 11286713
TI  - The role of molecules that mediate apoptosis in T-cell selection.
AB  - The T-cell repertoire is generated as a result of selection processes that happen
      in the thymus. The molecular basis of these processes is beginning to be
      elucidated and many of the molecules identified have a role in regulating cell
      death. These molecules range from orphan nuclear receptors and transcription
      factors to cyclin-dependent kinase 2 and Bcl2 family members.

PMID- 11286714
TI  - IL-12 gene therapy for cancer: in synergy with other immunotherapies.
AB  - In preclinical models of cancer, gene therapy with interleukin 12 (IL-12) has
      reached unprecedented levels of success when combined with immunotherapy
      approaches such as gene transfer of other cytokines and/or chemokines,
      costimulatory molecules or adoptive cell therapy. These combinations have been
      found to produce synergistic rather than additive effects. Meanwhile, IL-12 gene
      therapy is beginning clinical testing as a single agent, but combination
      strategies are at hand.

PMID- 11286715
TI  - Is TGF-beta1 the key to suppression of human asthma?
AB  - Transforming growth factor beta1 (TGF-beta1) is produced by many types of cells
      that are activated in the asthmatic response. Recent studies have highlighted
      this cytokine as an important negative regulator in an experimental model of
      asthma. Although the role of TGF-beta1 in human asthma remains obscure, data
      derived from animal models have encouraged the further investigation of such
      suppression mechanisms in order to develop novel therapies for asthma.

PMID- 11286716
TI  - Effector and regulatory T cells in allergic contact dermatitis.
AB  - Allergic contact dermatitis is a prototypic T-cell-mediated disease that has a
      socio-economic impact in industrialized countries. Here, Andrea Cavani and
      colleagues highlight recent developments in the T-cell-based effector and
      regulatory mechanisms of this common skin disorder.

PMID- 11286727
TI  - A symbiotic concept of autoimmunity and tumour immunity: lessons from vitiligo.
AB  - Vitiligo is a skin disease in which melanocytes (MCs) are eradicated from
      lesional epidermis, resulting in disfiguring loss of pigment. MCs are destroyed
      by MC-reactive T cells, as well as other non-immune and immune components.
      Similarities exist between the autoimmunity observed in vitiligo and the tumour
      immunity observed in melanoma immuno-surveillance. An analysis of these
      mechanisms might lead to the development of new therapies for both vitiligo and
      melanoma.

PMID- 11286728
TI  - Human memory T cells: lessons from stem cell transplantation.
AB  - Animal models have revealed the rules for the organization of mature T-cell
      pools. However, in humans, little is known about memory T cells, which differ in
      lifespan and in the number of times that the same antigen is encountered. Here,
      Nathalie Rufer and colleagues discuss their findings in stem-cell-transplanted
      patients, which provide interesting data on the human T-cell compartment.

PMID- 11286729
TI  - Dendritic cells resurrect antigens from dead cells.
AB  - Antigens that do not normally access the cytoplasm of antigen-presenting cells,
      such as certain tumor and viral antigens, become targets of cytotoxic T
      lymphocytes (CTLs). Over the past 25 years, substantial evidence has emerged for
      an 'exogenous' pathway for loading MHC class I molecules. Dendritic cells are
      potent stimulators of T-cell responses and can induce CD8(+) CTLs by phagocytosis
      of dead tumor or virus-infected cells. Here, Marie Larsson and colleagues discuss
      the role of dendritic cells in stimulating MHC class I-restricted T-cell
      responses by exogenous routes.

PMID- 11286730
TI  - Immunotherapeutic gene transfer into muscle.
AB  - Immuno-gene therapy can be advantageously performed with nonviral approaches.
      Genes that encode regulatory cytokines or inflammatory cytokine inhibitors can be
      delivered intramuscularly and expressed for weeks or months. This type of gene
      transfer into muscle has been shown to ameliorate several autoimmune diseases and
      is relevant to the development of effective DNA vaccines in autoimmune diseases,
      infectious diseases and cancer.

PMID- 11286731
TI  - Notch1 and T-cell development: insights from conditional knockout mice.
AB  - Notch proteins influence cell-fate decisions in many developmental systems. Gain
      of-function studies have suggested a crucial role for Notch1 signaling at several
      stages during lymphocyte development, including the B/T, alphabeta/gammadelta and
      CD4/CD8 lineage choices. Here, we critically re-evaluate these conclusions in the
      light of recent studies that describe inducible and tissue-specific targeting of
      the Notch1 gene.

PMID- 11286732
TI  - TB vaccines: progress and problems.
AB  - Tuberculosis (TB) is the biggest killer worldwide of any infectious disease, a
      situation worsened by the advent of the HIV epidemic and the emergence of multi
      drug resistant strains of Mycobacterium tuberculosis. The existing vaccine,
      Mycobacterium bovis bacille Calmette-Guerin (BCG), has proven inefficient in
      several recent field trials. There is currently intense research using cutting
      edge vaccine technology to combat this ancient disease. However, it is necessary
      to understand why BCG has failed before we can rationally develop the next
      generation of vaccines. Several hypotheses that might explain the failure of BCG
      and the strategies designed to address these shortcomings are discussed.

PMID- 11286733
TI  - Infection and heart disease: the current situation.

PMID- 11286734
TI  - RNA polymerase III: a fundamental mechanism contributing to transformation.

PMID- 11286735
TI  - Rare bone disorders reveal a key metabolic gene.

PMID- 11286736
TI  - Tracking down a genetic culprit in type 2 diabetes.

PMID- 11286739
TI  - 'Forkhead' gene expression balanced on a knife-edge.

PMID- 11286742
TI  - Are eosinophils out of asthma?

PMID- 11286755
TI  - Is oxidative stress central to the pathogenesis of chronic obstructive pulmonary
      disease?
AB  - There is now considerable evidence for an increased oxidant burden in patients
      with chronic obstructive pulmonary disease (COPD). Oxidative stress is a critical
      feature in the pathogenesis of COPD, since it results in inactivation of
      antiproteinases, airspace epithelial injury, MUCUS HYPERSECRETION, increased
      influx of neutrophils into the lungs, transcription factor activation and gene
      expression of pro-inflammatory mediators. Antioxidants should therefore not only
      protect against the direct injurious effects of oxidants, but also may
      fundamentally alter the inflammatory events which have a central role in the
      pathogenesis of COPD.

PMID- 11286756
TI  - Xenotransplantation, endogenous pig retroviruses and the precautionary principle.
AB  - Xenotransplantation poses challenges to scientists, ethicists and clinicians.
      Recent studies of the role of endogenous retroviruses suggest that these agents
      could threaten the safety of porcine xenotransplantation both for the recipient
      of a transplant, and possibly for people who have contact with that patient.
      Although the risk of such complications is low, the history of recent infectious
      diseases suggests that the precautionary principle should be invoked.

PMID- 11286757
TI  - The molecular basis of copper-transport diseases.
AB  - Copper (Cu) is a potentially toxic yet essential element. MENKES DISEASE, a
      copper deficiency disorder, and WILSON DISEASE, a copper toxicosis condition, are
      two human genetic disorders, caused by mutations of two closely related Cu
      transporting ATPases. Both molecules efflux copper from cells. Quite diverse
      clinical phenotypes are produced by different mutations of these two Cu
      transporting proteins. The understanding of copper homeostasis has become
      increasingly important in clinical medicine as the metal could be involved in the
      pathogenesis of some important neurological disorders such as Alzheimer's
      disease, motor neurone diseases and prion diseases.

PMID- 11286758
TI  - Genetic clues to the molecular basis of tobacco addiction and progress towards
      personalized therapy.
AB  - The molecular processes that underlie addiction are beginning to unfold.
      Genetically determined variations in dopaminergic neurotransmission predispose to
      nicotine dependence. In addition, tobacco use is likely to be governed by the
      rate at which smokers metabolize nicotine. Functional polymorphisms in CYTOCHROME
      P450 monooxygenases that metabolize nicotine have now been defined and it should
      soon be possible to identify fast nicotine metabolizers by DNA analysis. Here, we
      review the key neurotransmitter receptors and metabolic enzymes implicated in
      tobacco dependence. We explore the potential benefits of classifying smokers
      according to the molecular aetiology of their habit. One major benefit will be in
      planning effective strategies for smoking cessation. Methods of typing for
      alleles related to smoking behavior that might be suitable for use in clinical
      practice in the future will also be discussed

PMID- 11286759
TI  - Microsatellite instability as a tool for the classification of gastric cancer.
AB  - Microsatellite instability (MSI) is a common feature of gastric cancers that
      reflects underlying mismatch-repair deficiency in the tumor, caused most
      frequently by methylation of the hMLH1 promoter. Tumors with MSI have been found
      to inactivate certain target genes by permitting an increased frequency of
      mutations in mononucleotide runs in their coding regions. Gastric tumors with MSI
      have a distinct clinicopathological profile with a relatively good prognosis.
      Using the simple and robust methodologies available, MSI detection in
      gastrointestinal tumors promises to be one of the first widely used molecular
      prognostic tests for human cancer. Here, we review the molecular context of this
      exciting prospect with respect to one of the world's most prevalent cancers, that
      of the stomach.

PMID- 11286760
TI  - DHEA: a novel adjunct for the treatment of male trauma patients.
AB  - Despite significant advances in the management of trauma victims, traumatic
      injury with the ensuing sepsis and multiple organ failure remains the leading
      cause of death between the ages of 18 and 44 in the USA. Recently, interest in
      the clinically and experimentally observed gender dimorphic response to traumatic
      injury has led to the possibility of modulating cell and organ functions
      following trauma and hemorrhagic shock by the administration of sex steroids.
      Here, we review the effects of the adrenal steroid dehydroepiandrosterone (DHEA),
      a precursor of sex steroid synthesis, on organ and immune functions following
      trauma-hemorrhage, and its potential as a novel therapy for improving the
      depressed cell and organ functions in trauma patients.

PMID- 11286761
TI  - Disease model: dissecting the pathogenesis of the measles virus.
AB  - Host-pathogen interactions of measles virus (MV), a leading cause of childhood
      mortality worldwide, are still poorly understood. Using transgenic mice that
      express the human MV receptor CD46, we generated models to study the pathogenesis
      of MV infection of the central nervous system (CNS) and immune system. CNS
      infection in CD46 transgenic mice allows replication and spread throughout
      neurons, inflammation, and ultimately death of the animals. CD46-transgenic mice
      can also be used to study immunosuppression, a hallmark of measles. Together with
      mouse knockout technology and a system for generating recombinant MVs, CD46
      transgenic mice will ultimately lead to a better understanding of both viral and
      host factors contributing to disease.

PMID- 11286762
TI  - Bruce Spiegelman interviewed by David Bradley.

PMID- 11286763
TI  - Strategies for improved antigen delivery into dendritic cells.
AB  - Efficacious vaccines against cancers and infectious diseases will, in general,
      need to elicit comprehensive immune responses, including cytotoxic T lymphocyte
      activity. Because of their unique T cell stimulatory capacities, dendritic cells
      (DC) have emerged as the most potent antigen-presenting cell. Vaccination
      strategies should therefore aim at the acquisition and display of the antigen(s)
      of choice by DC. Results from vaccination studies, in animal models and in
      humans, stress the need for optimized antigen delivery systems to DC, to increase
      vaccination efficacy as well as to improve control on the immunological outcome.
      Here, we discuss the advantages and limitations of several recently described
      methodologies for antigen delivery into DC.

PMID- 11286764
TI  - A new chapter in Rh research: Rh proteins are ammonium transporters.
AB  - Occasionally, an original research paper has an unusually significant impact on a
      particular research field. Such a paper, published recently in Nature Genetics,
      describes the uncovering of the functional role of the Rh protein family--the
      proteins that express the Rh blood group antigens. Marini et al. (1) demonstrate
      how two human Rh glycoproteins can correct ammonium transport deficiency in
      mutant yeast cells. Rh proteins are therefore ammonium transporters--a role that,
      in vertebrates, has remained previously uncharacterized. These data herald a new
      era in Rh protein research, beyond their role as blood group antigens, and into
      the characterization of ammonium transport mechanisms, notably in the kidney.

PMID- 11286765
TI  - Endostatin "cell factories" shrink rodent brain tumors.

PMID- 11286766
TI  - Can staphylococcal superantigens be neutralized by healthy infants?

PMID- 11286767
TI  - Capsule essential for fatal tropical disease pathogen.

PMID- 11286768
TI  - Inverted chemistry--from drug to prodrug.

PMID- 11286769
TI  - Homing in on Russell-Silver.

PMID- 11286770
TI  - Antisense therapy to ameliorate DMD.

PMID- 11286771
TI  - Screening for schizophrenia.

PMID- 11286772
TI  - Tracking genes.

PMID- 11286773
TI  - Night owls and morning larks.

PMID- 11286774
TI  - Insights into eating disorders.

PMID- 11286775
TI  - Niemann-Pick disease genes.

PMID- 11286777
TI  - Looking into mirror movement disorder.

PMID- 11286776
TI  - Alternatives to Viagra.

PMID- 11286778
TI  - Ups and downs.

PMID- 11286779
TI  - PubMed Central.

PMID- 11286780
TI  - Brain iron transport and neurodegeneration.
AB  - Despite years of investigation, it is still not known why iron levels are
      abnormally high in some regions of the brain in neurodegenerative disorders.
      Also, it is not clear whether iron accumulation in the brain is an initial event
      that causes neuronal death or is a consequence of the disease process. Here, we
      propose that iron and iron-induced oxidative stress constitute a common mechanism
      that is involved in the development of neurodegeneration. Also, we suggest that,
      at least in some neurodegenerative disorders, brain iron misregulation is an
      initial cause of neuronal death and that this misregulation might be the result
      of either genetic or non-genetic factors.

PMID- 11286781
TI  - Prions: disease propagation and disease therapy by conformational transmission.
AB  - Transmissible spongiform encephalopathies - also known as prion-related diseases 
      are a group of fatal neurodegenerative disorders associated with the misfolding
      of prion protein. Several unprecedented scientific findings, which have directly
      confronted popular dogmas in biology, have put prion research in the spotlight.
      The experimental evidence supports an entirely novel disease mechanism, involving
      disease transmission by replication of protein conformation. Here, we describe
      exciting scientific findings that make the prion field attractively heretical,
      and we propose the transmission of protein conformation as a novel approach to
      producing drugs to combat a variety of diseases.

PMID- 11286782
TI  - Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and
      therapy.
AB  - Multiple sclerosis is a chronic inflammatory disease of the nervous system in
      which a T-cell-mediated inflammatory process is associated with destruction of
      myelin sheaths. Although demyelination is the primary event, axons are also
      destroyed in the lesions, and the loss of axons correlates with permanent
      functional deficit. Here, we discuss evidence that demyelination and axonal
      destruction follow different pathogenetic pathways in subgroups of patients. This
      might, at least in part, explain the heterogeneity in genetic susceptibility,
      clinical presentation and response to treatment observed between individuals.

PMID- 11286783
TI  - Molecular basis of partial lipodystrophy and prospects for therapy.
AB  - Lipodystrophy is characterized by altered partition of adipose tissue. Despite
      heterogeneous causes, which include genetic, autoimmune and drug-induced forms,
      lipodystrophy syndromes have similar metabolic attributes, including insulin
      resistance, hyperlipidemia and diabetes. The mechanisms underlying the insulin
      resistance are unknown. One form of lipodystrophy, namely Dunnigan-type familial
      partial lipodystrophy (FPLD) was shown to result from mutations in the LMNA gene,
      which encodes nuclear lamins A and C. Although the relationship between the
      mutations in the nuclear envelope and insulin resistance is unclear at present,
      these findings might eventually be shown to have relevance for the common insulin
      resistance syndrome and for drug-associated lipodystrophies.

PMID- 11286784
TI  - Biological effects of growth hormone and its antagonist.
AB  - Serum levels of growth hormone (GH) can vary. Low levels of GH can result in a
      dwarf phenotype and have been positively correlated with an increased life
      expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed
      acromegaly and has been implicated in diabetic eye and kidney damage.
      Additionally the GH/IGF-1 system has been postulated as a risk factor for several
      types of cancers. Thus both elevated and suppressed circulating levels of GH can
      have pronounced physiological effects. More than a decade ago the first drug of a
      new class, a GH antagonist, was discovered. This molecule is now being tested for
      its ability to combat the effects of high circulating levels of GH. Here, we
      discuss some of the detrimental actions of GH, and how a GH antagonist can be
      used to combat these effects.

PMID- 11286785
TI  - Disease model: photoreceptor degenerations.
AB  - Retinal diseases can be caused by genetic or non-genetic factors, and typically
      involve specific cell layers within the retina. A large number of simple
      Mendelian gene defects are known to affect the photoreceptor cell layer. As
      photoreceptor cells cannot be maintained in vitro, the study of animal models is
      instrumental in understanding the disease process and in testing therapeutic
      approaches. This review briefly summarizes those animal models of photoreceptor
      diseases with defined genotypes.

PMID- 11286786
TI  - Disease model: pulmonary tuberculosis.
AB  - In spite of a massive effort to apply the tools currently available for
      tuberculosis (TB) control, both in this country and abroad, it is clear that
      complicating factors [for example, HIV co-infection, drug resistance, lack of
      patient compliance with chemotherapy, variable efficacy of Bacille Calmette
      Guerin (BCG) vaccine] will prevent disease control unless new drugs, vaccines and
      diagnostic tests are developed (1). The publication of the complete genome
      sequence of Mycobacterium tuberculosis in 1998 (2) has facilitated a directed
      search for virulence genes, new drug targets, and vaccine antigens. This research
      effort has been made possible by the availability of highly biologically relevant
      animal models of pulmonary TB ((3)).

PMID- 11286787
TI  - Hair cell function - it's all a matter of organization.

PMID- 11286788
TI  - Rationale for malaria anti-toxin therapy.

PMID- 11286789
TI  - One million insects--a lot of parasites?

PMID- 11286794
TI  - Possible modes of action of the artemisinin-type compounds.
AB  - Artemisinin-type compounds are used for the treatment of uncomplicated and severe
      forms of malaria. They reduce parasitaemia more rapidly than any other
      antimalarial compound known, and are effective against multidrug-resistant
      parasites. However, uncertainties remain as to how they act on the parasite and
      cause toxicity. In this review, we summarize current ideas.

PMID- 11286795
TI  - Do basophils play a role in immunity against parasites?
AB  - The link between parasites and eosinophilia has been known for more than a
      century, although the role of eosinophils in host protection is still an open
      issue. Much less appreciated, however, is the concurrent systemic induction of a
      related cell type, the basophil, in parasitized hosts. To date, little is known
      about the role of basophils in immunity against parasites, but recent evidence
      points to a possible crucial role in the initiation of T-helper type 2 responses
      in the host. In this article, we review the current understanding of parasitic
      infections and basophils and discuss their putative role in immunity.

PMID- 11286796
TI  - The role of mucins in host-parasite interactions: Part II - helminth parasites.
AB  - Some parasites express mucin-like molecules. These have possible roles in
      attachment and invasion of host cells and in the avoidance of host immune
      processes. Enzymes of parasite origin might also facilitate infection, either by
      degrading host mucus barriers or by generating binding sites on host cells. Host
      mucins have roles in preventing parasite establishment or in parasite expulsion.
      They, in turn, might be exploited by parasites, either as sources of fuel or
      binding sites, or as host-finding targets. Here, we describe the biochemical
      properties of mucins and mucin-like molecules in relation to interactions
      (established and putative) between helminth parasites and their hosts.

PMID- 11286798
TI  - Dinitroaniline herbicides against protozoan parasites: the case of Trypanosoma
      cruzi.
AB  - The drugs presently in use against Chagas disease are very toxic, inducing a
      great number of side effects. Alternative treatments are necessary, not only for
      Chagas disease but also for other diseases caused by protozoan parasites where
      current drugs pose toxicity problems. The plant microtubule inhibitor trifluralin
      has previously been tested with success against Leishmania, Trypanosoma brucei
      and several other protozoan parasites. Trypanosoma cruzi, the causative agent of
      Chagas disease, is also sensitive to the drug. This sensitivity has been
      correlated with the deduced amino acid sequences of alpha- and beta-tubulin of T.
      cruzi as compared with plant, mammal and other parasite sequences.

PMID- 11286799
TI  - Nucleoside transporters of parasitic protozoa.
AB  - Protozoan parasites are incapable of synthesizing purine nucleotides de novo and
      so must salvage preformed purines from their hosts. This process of purine
      acquisition is initiated by the translocation of preformed host purines across
      parasite or host membranes. Here, we report upon the identification and isolation
      of DNAs encoding parasite nucleoside transporters and the functional
      characterization of these proteins in various expression systems. These potential
      approaches provide a powerful approach for a thorough molecular and biochemical
      dissection of nucleoside transport in protozoan parasites.

PMID- 11286800
TI  - Child mortality and malaria transmission intensity in Africa.
AB  - The desirability of controlling malaria transmission in the areas of highest
      endemicity of Plasmodium falciparum has long been debated. Most recently, it has
      been claimed that rates of malaria morbidity are no higher in areas of very high
      transmission in Africa than they are in places with lower inoculation rates. We
      now review the literature on the relationship of morbidity and mortality to
      malaria transmission intensity, and have linked published child mortality and
      malaria transmission rates to examine how age-specific mortality actually varies
      with the inoculation rate of P. falciparum.

PMID- 11286801
TI  - In vitro cultivation and characterization of axenic amastigotes of Leishmania.
AB  - The establishment of axenic cultures of the amastigote stage of Leishmania is
      important to understand the mechanisms regulating the differentiation, survival
      and pathogenicity of the parasite with a view to develop and identify molecular
      and chemotherapeutic targets. Recent developments in axenic culture and the
      characterization of amastigotes of different species of Leishmania are discussed.

PMID- 11286804
TI  - The production of reactive oxygen species by irradiated camphorquinone-related
      photosensitizers and their effect on cytotoxicity.
AB  - Camphorquinone (CQ) is widely used as an initiator in modern light-cured resin
      systems but there are few reports about its effects on living cells. To clarify
      the mechanism of photosensitizer-induced cytotoxicity, the production of
      initiator radicals and subsequent reactive oxygen species (ROS) by CQ, benzil
      (BZ), benzophenone (BP), 9-fluorenone (9-F) in the presence of the reducing agent
      (2-dimethylaminoethyl methacrylate or N,N-dimethyl-p-toluidine, DMT) with visible
      light irradiation was examined in a cell or cell-free system. Initiator radical
      production was estimated by the reduction rate of 1,1-diphenyl-2-picrylhydrazyl
      and by the conversion of poly-triethyleneglycol dimethacrylate; the results
      indicated that CQ/DMT had the highest activity among them. The cytotoxic effects
      of the photosensitizers on both human submandibular gland (HSG) adenocarcinoma
      cell line and primary human gingival fibroblast (HGF) showed that the 50% toxic
      concentration (TC(50)) declined in the order: CQ>BP>9-F>BZ. ROS produced in HSG
      or HGF cells by elicited, irradiated photosensitizers were evaluated in two
      different assays, one using adherent cell analysis and sorting cytometry against
      adherent cells and the other, flow cytometry against floating cells, with
      fluorescent probes. ROS production was dose- and time- dependent, and declined in
      the order: BZ>9-F>BP>CQ. Cytotoxic activity was correlated with the amount of
      ROS. Cytotoxicity and ROS generation in HGF cells was significantly lower than in
      HSG cells. ROS induced by aliphatic ketones (CQ) were efficiently scavenged by
      hydroquinone and vitamin E, whereas those by aromatic ketones (9-F) were
      diminished by mannitol and catalase, suggesting that OH radicals were involved in
      ROS derived from 9-F. A possible link between the cytotoxic activity and ROS is
      suggested.

PMID- 11286805
TI  - An immuno-light- and electron-microscopic study of the expression of bone
      morphogenetic protein-2 during the process of ectopic bone formation in the rat.
AB  - Immunolocalization of endogenous bone morphogenetic protein-2 (BMP-2) was
      investigated during the process of ectopic bone formation induced by recombinant
      human BMP-2 (rhBMP-2). Pellets consisting of 5 microg of rhBMP-2 and 6 mg of
      atelopeptide type I collagen (AC) were implanted into the calf muscles of 6-week
      old rats. On days 7, 10, 14, 21 and 28 after implantation, tissue specimens were
      removed and examined immunohistochemically by light and electron microscopy after
      incubation with anti-BMP-2 monoclonal antibodies. Immunolocalization by light
      microscopy showed BMP-2 in chondrocytes at the pellet rim on days 7 and 10, in
      osteocyte-like cells in the chondroid matrix on day 14, and in osteocytes in the
      newly formed bone on days 21 and 28 after implantation. Ultrastructurally, on
      days 7 and 10 after implantation, immunolabelling for BMP-2 was aggregated in
      vesicle-like matrices released from mature chondrocytes in the chondroid matrix.
      On day 14, immunolabelling against BMP-2 had accumulated in vesicle-like matrices
      embedded in the calcified cartilage, in the cytoplasmic vacuoles of chondroclasts
      absorbing the matrix, and at the resorption surface of the calcified cartilage.
      On days 21 and 28, BMP-2 immunolabelling was seen in the osteoid layer and
      osteocyte lacunae. These results suggest that the chondrocytes and osteocytes
      induced by rhBMP-2 produce endogenous BMP-2. It seems that part of the endogenous
      BMP-2 that accumulated in the chondroid matrix was absorbed by chondroclasts and
      then participated in the osteoblastic differentiation of immature mesenchymal
      cells. This study indicates that, in addition to the implanted exogenous rhBMP-2,
      endogenous BMP-2 plays an important part in the maintenance of the bone-formation
      cascade during ectopic osteoinduction.

PMID- 11286806
TI  - Relationships between medication intake, complaints of dry mouth, salivary flow
      rate and composition, and the rate of tooth demineralization in situ.
AB  - The aim of this study was to describe the relationships between the rate of tooth
      demineralisation and medication intake, subjective feeling of dry mouth, saliva
      flow, saliva composition and the salivary level of lactobacilli. The study group
      consisted of 28 subjects that were divided into three groups according to their
      unstimulated whole saliva flow rate. Group 1 had an unstimulated saliva low rate
      < or =0.16 ml/min (n=10), group 2 had one from 0.17--0.30 ml/min (n=9), and group
      3 had one >0.30 ml/min (n=9). The rate of tooth demineralization was determined
      as mineral loss assessed by quantitative microradiography of human root surfaces,
      exposed to the oral environment for 62 days in situ. The unstimulated and
      stimulated saliva flow rates, pH, bicarbonate, calcium, phosphate, and protein
      concentrations, as well as the degree of saturation of saliva with hydroxyapatite
      and the saliva buffer capacity were determined. The results showed that almost
      all subjects developed demineralization, albeit at highly varying rates. Eighty
      five percent of the subjects in group 1, 33% of the subjects in group 2, and 0%
      of the subjects in group 3 developed mineral loss above the mean mineral loss for
      all the root surfaces in this experiment. Futhermore, group 1 differed
      significantly from groups 2 and 3 in having a higher medication intake, a more
      pronounced feeling of dry mouth, lower stimulated saliva flow rate, lower
      stimulated bicarbonate concentration, lower unstimulated and stimulated
      compositional outputs (bicarbonate, calcium, phosphate, and protein), and a
      higher Lactobacillus level. The best explanatory variable for high mineral loss
      in this study was a low unstimulated saliva flow rate. In conclusion, our results
      suggest that an unstimulated salivary flow rate < or =0.16 ml/min as described by
      Navazesh et al. (1992), is a better indicator of increased caries risk due to
      impaired salivation, than the currently accepted definition of hyposalivation
      (unstimulated saliva flow rate < or =0.10 ml/min), which relates to the function
      of the salivary glands (Sreebny, 1992).

PMID- 11286807
TI  - A longitudinal study of time trends in the eruption of permanent teeth in Danish
      children.
AB  - The purpose was: (1) to estimate mean eruption times of permanent teeth in Danish
      schoolchildren for the birth cohorts from 1969 to 1982; and (2) to determine any
      time trends in eruption. For teeth with a low proportion of aplasia, the
      distribution of the eruption time was close to normal. For teeth with a higher
      proportion of aplasia there was a slight deviation from the normal distribution
      in the right-hand part of the distribution. For erupted teeth, the time to
      eruption was, however, again very close to the normal distribution. A small, but
      statistically significant, increase in mean eruption times was found for both
      sexes and almost all teeth. Averaged over all teeth the increase was 1.5 days per
      year (95% CI: 0.9--2.2) for boys and 2.6 days per year (95% CI: 2.2--2.9) for
      girls.

PMID- 11286808
TI  - Excitatory actions of experimental muscle pain on early and late components of
      human jaw stretch reflexes.
AB  - It has recently been shown that a slow stretch evokes a short-latency (probably
      monosynaptic) and a long-latency (polysynaptic) reflex response in human jaw
      closing muscles. The effect of nociceptive muscle input on the fusimotor system
      has not been investigated in detail. In order to investigate the effect of
      sustained muscle pain on the jaw stretch reflex, two main experiments were
      performed. Stretch reflex responses were evoked in the masseter and temporalis
      muscles by slow stretches (1-mm displacement, 40-ms ramp time) before, during and
      15 min after a period of experimentally induced muscle pain. In experiment I, a
      dose of 1.0 M hypertonic or 154 mM isotonic (control) saline was infused in
      random order into the left masseter for up to 15 min (n=12). The level of
      excitation of the left masseter at 15% maximal voluntary contraction was
      controlled by visual feedback of the surface EMG (sEMG). In experiment II, a dose
      of 1.0 M saline was infused into the left masseter but with feedback from the
      sEMG of the right masseter (n=12). In a control experiment, both sEMG and
      intramuscular EMG (imEMG) were recorded from the left and right masseters; the
      feedback was from imEMG of the left masseter (n=12). The early (onset: 9--10 ms)
      and late (duration from 25 to 40 ms) reflex components were recorded and analysed
      in all experiments. Infusion of 1.0 M saline caused moderate pain (mean score on
      a Visual Analogue Pain Scale: 4.9--5.0 cm). The peak-to-peak amplitude of the
      early reflex component in the painful masseter normalized to the pre-stimulus EMG
      activity was significantly higher during the pain than the pre- and post-infusion
      conditions in all experiments. The normalized area of the late reflex component
      in the painful masseter was significantly larger than in the pre-infusion
      condition in all experiments. Isotonic saline had no significant effect on the
      jaw stretch reflexes. These results indicate that experimental jaw-muscle pain in
      humans facilitates the early as well as the late component of the jaw stretch
      reflex response as revealed by both sEMG and imEMG. This effect appears to be
      independent of the level of excitation of the muscle and not related to volume
      effects of the injected saline. A change in the sensitivity of the fusimotor
      system during muscle pain is suggested as an explanation.

PMID- 11286810
TI  - Expression of phosphodiesterase 3 in rat submandibular gland cell lines.
AB  - A recent preliminary (unpublished) study showed that phosphodiesterase (PDE) 3A
      and 3B are expressed in rat submandibular glands. Here, PDE3 activity was
      detected in homogenates of rat submandibular gland acinar epithelial (SMIE)
      cells, but not rat A5 (epithelial duct) cells. Most of the PDE3 activity in SMIE
      cells was recovered in the particulate fraction. Only PDE3B mRNA was detected by
      reverse transcription-polymerase chain reaction in RNA from SMIE cells. The
      nucleotide sequence of the fragment was identical to the sequence of rat PDE3B.
      The PDE3 specific inhibitor, OPC3689 (10 and 50 microM), inhibited the growth of
      SMIE cells (19 and 63%), but not A5 cells. As the submandibular gland contains
      many types of cells, these results indicate that PDE3B may regulate a cAMP pool
      that is important in submandibular gland acinar epithelial cell function.

PMID- 11286809
TI  - Effects of ovariectomy and/or dietary calcium deficiency on bone dynamics in the
      rat hard palate, mandible and proximal tibia.
AB  - The effects of ovariectomy and/or dietary calcium deficiency on bone dynamics
      were examined by comparing the histomorphometric changes in these bones. Five
      groups of rats were studied, (1) unoperated basal controls; (2) sham-operated,
      fed on a normal-calcium diet; (3) ovariectomized, fed on a normal-calcium diet;
      (4) sham-operated, fed on a calcium-deficient diet; (5) ovariectomized, fed on a
      calcium-deficient diet. The basal controls were killed at 6 weeks of age, and the
      remaining groups were killed at 18 weeks of age. The hard palate, mandible and
      proximal tibia were processed undemineralized for quantitative bone
      histomorphometry. Bone volume, eroded surface, osteoid surface and bone-formation
      ratio were calculated. A significant age-related increase in bone volume and a
      significant decrease in bone formation were observed in the hard palate and
      mandible, whereas no significant age-related increase in bone volume could be
      found in the tibia. In the hard palate, ovariectomy neither inhibited age-related
      increases in bone volume nor affected bone dynamics, while both the combined
      ovariectomy and dietary calcium deficiency and dietary calcium deficiency alone
      led to bone loss and increased bone turnover. In contrast, in the mandible and
      proximal tibia, ovariectomy alone as well as dietary calcium deficiency led to
      bone loss and increased bone turnover. Ovariectomy, therefore, produced no
      significant changes in the hard palate, but affected bone dynamics in the
      mandible and tibia. However, dietary calcium deficiency induced bone loss and
      increased bone turnover in the hard palate, mandible and proximal tibia,
      independently of ovariectomy.

PMID- 11286811
TI  - Novel COL1A1 mutation (G559C) [correction of G599C] associated with mild
      osteogenesis imperfecta and dentinogenesis imperfecta.
AB  - A genotype-phenotype analysis of a three-generation family segregating for an
      autosomal-dominant osteogenesis imperfecta (OI) variant is reported here. The
      family was ascertained through the presentation of a proband concerned about
      discoloration of her teeth, found to be dentinogenesis imperfecta (DGI).
      Examination of 36 family members identified 15 individuals with DGI. Linkage
      studies were performed for genetic markers from candidate intervals known to
      contain genes responsible for DGI on chromosomes 4q, 7q, and 17q. Conclusive
      evidence for linkage of DGI was obtained to genetic markers on chromosome 17q21
      q22 (DLX-3, Z(max) = 5.34, theta = 0.00). All DGI-affected family members shared
      a common haplotype, which was not present in individuals without DGI. Haplotype
      analysis sublocalized the gene to a 5-cM genetic interval that contained the
      collagen 1 alpha 1 (COL1A1) gene. More than 150 different COL1A1 gene mutations
      have been associated with various forms of OI, and five of these have been
      associated with DGI and type IV OI. After excluding these five mutations,
      mutational analysis was performed on the remaining exons including intron--exon
      boundaries, which resulted in identification of a Gly559Cys mutation in exon 32,
      present in all DGI-affected family members. Clinical features segregating with
      this G559C mutation included hyperextensible joints, joint pain and an increased
      propensity for bone fractures with moderate trauma. This is the first report of
      joint pain associated with a COL1A1 mutation and DGI. The mild skeletal features
      and reduced penetrance of the non-dental findings illustrate the importance of
      genetic evaluations for families with a history of DGI.

PMID- 11286812
TI  - Spatial distribution of vital and dead microorganisms in dental biofilms.
AB  - To examine the spatial structure of dental biofilms a vital fluorescence
      technique was combined with optical analysis of sections in a confocal laser
      scanning microscope (CLSM). Enamel slaps were worn in intraoral splints by three
      volunteers for five days to accumulate smooth-surface plaque. After vital
      staining with fluorescein diacetate and ethidium bromide the specimens were
      processed for CLSM examination. Optical sections 1 microm apart were analysed in
      the z-axis of these dental biofilms. One of the films was 15 microm high, sparse
      and showed low vitality, i.e. <16%, while the others were taller (25 and 31
      microm) and more vital, i.e. up to 30 and 69%, respectively. In all instances the
      bacterial vitality increased from the enamel surface to the central part of the
      plaque and decreased again in the outer parts of the biofilm. The spatial
      arrangement of the microorganisms in the biofilm showed voids outlined by layers
      of vital bacteria, which themselves were packed in layers of dead material.

PMID- 11286813
TI  - Neuropsychological performance and spectrum personality traits in the relatives
      of patients with schizophrenia and affective psychosis.
AB  - Neuropsychological deficits are found in both schizophrenic patients and their
      relatives, and some studies have shown similar, but less severe, deficits in
      affective psychotic patients and their relatives. We set out to establish: (a)
      whether schizophrenia spectrum personality traits are more common in the
      relatives of schizophrenic patients than, in the relatives of affective psychotic
      patients; and (b) what the relation is between spectrum personality traits and
      neuropsychological deficits in these relatives. Relatives were interviewed using
      the International Personality Disorder Examination (IPDE), and also completed the
      National Adult Reading Test (NART), the Trail Making Test (TMT; Parts A and B)
      and Thurstone's Verbal Fluency Test (TVFT). Spectrum personality traits were
      equally common in 129 relatives of schizophrenic patients and 106 relatives of
      affective psychotic patients, but the performance of the former group was
      inferior to that of the latter on the NART and the TVFT. Relatives with high
      paranoid traits had lower NART scores than relatives without such personality
      traits; similarly, those with high schizoid traits took longer to complete the
      TMT, part B, than those without such traits; and relatives with high schizotypal
      traits generated significantly fewer words on the TVFT than those without such
      traits. We conclude that relatives of schizophrenic and affective psychotic
      patients share a propensity to schizophrenia spectrum traits, but relatives of
      the former have poorer neuropsychological performance. Furthermore, there exists
      an association between neuropsychological deficits and spectrum traits in both
      groups of relatives; in particular those with high paranoid traits have lower IQ
      scores than their less paranoid counterparts.

PMID- 11286814
TI  - Early, non-psychotic deviant behavior in schizophrenia: a possible endophenotypic
      marker for genetic studies.
AB  - Early non-psychotic deviance occurs in some, but not all, pre-schizophrenic
      patients and has been linked to the later course of the disorder, suggesting its
      relationship with the schizophrenia syndrome. However, early deviance has rarely
      been explored as an endophenotypic marker in large samples of schizophrenic
      patients. We characterized the early childhood behavior and syndrome history of
      205 adults with DSM-IV schizophrenia. Sixty percent of our sample had poor
      socialization, extreme fears/chronic sadness, and/or attention
      impairment/learning disabilities beginning before age 10. The remaining 40% were
      without behavioral difficulties until the onset of schizophrenia. Logistic
      regression analyses suggested that the risk of syndrome onset before age 17 was
      2.5 times more likely among patients with poor socialization beginning before age
      10. Schizoaffective disorder was 3.75 times greater among patients with extreme
      fears/chronic sadness in childhood, and schizophrenic patients with early
      attention impairment/learning disabilities were 2 times more likely to have a 1
      degrees, 2 degrees or 3 degrees relative with schizophrenia. We concluded that
      early deviant behavior indicated a distinct subgroup of patients, and was linked
      to syndrome characteristics specifically relevant to genetic studies, in
      particular age at onset and family history of schizophrenia. Since early syndrome
      onset has been associated with specific genetic anomalies in other complex
      neuropathologic disorders, it may prove valuable to regard these early deviant
      behaviors as an indicator of early syndrome onset for future genetic studies of
      schizophrenia.

PMID- 11286815
TI  - Low birth weight, developmental milestones, and behavioral problems in Chinese
      children and adolescents.
AB  - This study examined the association of low birth weight (LBW) and developmental
      milestones with behavioral and emotional problems in a general population sample
      of 3344 Chinese children and adolescents aged 6-16 years in 1997. Parents
      completed a self-administrated questionnaire including information about birth
      weight and developmental milestones (i.e. lifting the head up, tooth eruption,
      speech, walking and bedwetting cessation), and the Child Behavioral Checklist
      (CBCL). Teachers completed the Teacher's Report Form (TRF) to assess classroom
      behavior problems. Results indicated that LBW and delayed developmental
      milestones were significantly associated with an increased risk for almost all
      parent- and teacher-reported behavioral problems after controlling for the
      potential effects of child's gender, age and birth order, parental ages at birth,
      education, occupation, complications at birth and number of children in the
      family. LBW was significantly associated with delay in achieving all
      developmental milestones including lifting of the head, tooth eruption, sitting
      without support, walking without help, speech as saying words with meaning, and
      bedwetting cessation. It is concluded that LBW and delayed early childhood
      development may predict the occurrence of a wide range of behavioral and
      emotional problems in later childhood and adolescence.

PMID- 11286816
TI  - Plasma GABA levels correlate with aggressiveness in relatives of patients with
      unipolar depressive disorder.
AB  - Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with
      depression, mania and alcoholism. Medications which increase plasma GABA improve
      symptoms of mood disorders and can decrease aggression. We examined the
      relationship between plasma GABA and aggressiveness on the Buss-Durkee Hostility
      Inventory in 77 psychiatrically healthy adults. In subjects selected for having a
      first-degree relative with primary unipolar depressive disorder (FH+, n=33),
      plasma GABA was negatively correlated with aggressiveness (beta=-0.338, P=0.036),
      as was age (beta=-0.483, P=0.005). A relationship between plasma GABA levels and
      aggressiveness was not observed in subjects with no such family history (FH-,
      n=44). Moreover, FH+ subjects had significantly lower plasma GABA concentrations
      than FH- subjects. These data suggest that low GABA levels may correlate with
      some aspects of aggressiveness and may be genetically regulated.

PMID- 11286817
TI  - Anxiety sensitivity does not predict fearful responding to 35% carbon dioxide in
      patients with panic disorder.
AB  - The aim of the present study was to examine the relationship between anxiety
      sensitivity, as measured by the Anxiety Sensitivity Index (ASI), and four
      dimensions of behavioural reactivity to a single inhalation of 35% carbon dioxide
      (CO(2)) in 31 patients with panic disorder. ASI scores correlated positively with
      baseline State-Trait Anxiety Inventory scores but did not correlate with post
      CO(2) scores. Correlational analyses revealed a significant, albeit modest,
      correlation between anxiety sensitivity and cognitive symptoms induced with
      CO(2). However, no significant association was found between anxiety sensitivity
      and other dimensions of CO(2)-induced anxiety, including severity of somatic
      symptoms, subjective levels of anxiety, fear or apprehension, and fear of the
      somatic symptoms induced by CO(2). Overall, these data do not support the view
      that anxiety sensitivity plays a key role in mediating behavioural sensitivity to
      CO(2) inhalation in panic disorder.

PMID- 11286818
TI  - Visual P300 and the self-directedness scale of the Temperament and Character
      Inventory.
AB  - Reduced amplitude of the P300 event-related brain potential has been associated
      with several psychopathological conditions and is thought to represent brain
      dysfunction in such conditions. Predisposition to personality disorders and
      psychopathology in general is also associated with low scores on the self
      directedness (SD) scale of the Temperament and Character Inventory. The present
      preliminary study investigated the relationship between amplitudes of P300
      elicited by rare target stimuli in a visual oddball task and SD scores in 58
      healthy participants. P300 was found to be significantly reduced in subjects with
      low SD, as supported by correlational analysis and by comparison of groups formed
      on the basis of SD scores. This finding may be relevant to prior findings
      indicating reduced P300 amplitudes in a variety of psychopathological conditions
      and suggests that a common vulnerability factor, reflected in the low SD
      personality scores, may contribute to the P300 reduction in psychiatric
      populations.

PMID- 11286819
TI  - Startle reactivity and PTSD symptoms in a community sample of women.
AB  - Exaggerated startle and PTSD symptoms have been investigated primarily in
      relation to acute or Type I stressors. The present study examined PTSD symptoms
      and startle eyeblink response in relation to chronic or Type II stressors. Type
      II stressors were operationally defined as high levels of childhood corporal
      punishment and high levels of current partner aggression. This study recruited a
      sample of 52 women from a metropolitan community and administered several
      questionnaires assessing experience of corporal punishment in childhood, current
      intimate partner aggression and level of PTSD symptoms. Following questionnaires,
      women were presented with eight auditory startle probes (white noise). Results
      showed that both childhood corporal punishment and intimate partner aggression
      were associated with women's PTSD symptom scores. However, only PTSD symptom
      scores were associated with reduced startle. Results are discussed in light of
      Type I and Type II stressors, and recent suggestions in the PTSD literature that
      a subgroup of individuals may experience physiological suppression rather than
      heightened physiological reactivity.

PMID- 11286820
TI  - Repetitive behaviors in Tourette's syndrome and OCD with and without tics: what
      are the differences?
AB  - Gilles de la Tourette Syndrome (GTS) and obsessive-compulsive disorder (OCD)
      share obsessive-compulsive phenomena. The aims of this study were to compare the
      OC symptom distribution between GTS and OCD and to investigate whether a
      subdivision of these phenomena into obsessions, compulsions and 'impulsions' is
      useful in distinguishing GTS and OCD patients. Thirty-two GTS, 31 OCD (10 with
      tics, 21 without tics) and 29 control subjects were studied using the Leiden
      repetitive behaviors semi-structured interview to assess GTS as well as OCD
      related behaviors. Each reported repetitive thought or action was evaluated on
      the presence of anxiety and on goal-directedness. This information was used to
      define whether the behavior was an obsession, compulsion, or 'impulsion'. Both
      the GTS and OCD study groups showed higher scores than control subjects on rating
      scales measuring depression, OC behavior and anxiety. In GTS, Y-BOCS severity
      scores and trait anxiety were lower than in the OCD groups. Furthermore, GTS
      patients differed from OCD patients in the distribution of symptoms. Aggressive
      repetitive thoughts, contamination worries and washing behaviors were reported
      more frequently by tic-free OCD, while mental play, echophenomena, touching and
      (self)-injurious behaviors were reported more frequently by GTS. OCD individuals
      with tics were intermediate, but closer to tic-free OCD. GTS individuals reported
      significantly more 'impulsions' and fewer obsessions and compulsions than OCD
      individuals with and without tics. Factor analysis revealed three factors
      accounting for 44% of the variance, resulting in an 'impulsive' factor related to
      GTS, a 'compulsive' factor related to OCD and an 'obsessive' factor related to
      tic-free OCD. In conclusion, OCD individuals reported more anxiety and goal
      directedness associated with their behaviors than did GTS subjects. The
      distinction between obsessions, compulsions and impulsions is of importance in
      identifying Tourette-related vs. non-Tourette-related repetitions.

PMID- 11286821
TI  - Increased titers of antibodies against streptococcal M12 and M19 proteins in
      patients with Tourette's syndrome.
AB  - It has been suggested that a post-streptococcal autoimmune process may be
      involved in the pathogenesis of a subgroup of children with tics and obsessive
      compulsive symptoms (PANDAS). Elevated antibody titers against streptococcal
      antigens have also been described in adult patients suffering from Tourette's
      syndrome (TS). In order to characterise further streptococcal antigens, we
      focussed on M proteins. M proteins are a major virulence factor of group A
      streptococci and known to evoke an immunologic cross-reaction with diverse
      epitopes of human tissue including brain tissue. Therefore, antibodies against M
      proteins may play a role in the pathophysiology of at least a subgroup of TS
      patients. Antibodies against M proteins were studied in 25 adult patients
      suffering from TS and 25 healthy controls after careful medical examination. The
      antibody titers against the peptides M1, M4, M6, M12 and M19 were estimated by
      ELISA. Our results show increased titers of antibodies against the streptococcal
      M12 and M19 proteins in TS patients as compared with controls, while antibody
      titers against M1, M4 and M6 did not differ between the TS and control groups.
      Elevated serum titers of antibodies against M12 and M19 proteins support the view
      that a streptococcus-induced autoimmune process may be involved in TS. The
      finding of a possible autoimmune origin of TS has implications for both
      pathophysiology and future therapeutic strategies.

PMID- 11286822
TI  - Measurement of inter-episode impulsivity in bipolar disorder.
AB  - We carried out a preliminary investigation of impulsivity in patients with
      bipolar I disorder not meeting criteria for active episodes. Barratt
      Impulsiveness Scale (BIS-11) scores were significantly higher in bipolar disorder
      than in control subjects. Laboratory measurements of impulsivity correlated with
      a BIS-11 score or severity of manic symptoms. Impulsivity in bipolar disorder may
      have both stable and state-dependent aspects.

PMID- 11286824
TI  - Investing in our future: listening to those who will take us where we need to go.

PMID- 11286825
TI  - Elevated cyclooxygenase-2 expression correlates with diminished survival in
      carcinoma of the cervix treated with radiotherapy.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      overall survival and prognostic factors in carcinoma of the cervix treated with
      radiation therapy. A clinicopathologic study was performed on 24 patients.
      METHODS AND MATERIALS: Formalin-fixed, paraffin-embedded tumor biopsies were
      stained for Cyclooxygenase-2 (COX-2), Topoisomerase I, Topoisomerase II, and p53.
      Clinical factors such as stage, grade, tumor size, pre- and post-treatment
      hemoglobin level, and radiotherapy dose were also evaluated. RESULTS: Median
      follow-up was 75 months for living patients. The only immunohistochemical or
      clinical factor that was associated with improved survival was decreased COX-2
      distribution staining. High COX-2 distribution staining was associated with
      decreased overall survival (p = 0.021) and decreased disease-free survival (p =
      0.015) by log-rank comparison of Kaplan-Meier survival curves. The 5-year overall
      survival rates for tumors with low vs. high COX-2 distribution values were 75%
      and 35%, respectively. COX-2 staining intensity was found to correlate positively
      with tumor size (p = 0.022). CONCLUSION: These findings indicate that increased
      expression of COX-2 portends a diminished survival in patients with invasive
      carcinoma of the cervix treated with radiotherapy. Because COX-2 is an early
      response gene involved in angiogenesis and inducible by different stimuli, these
      data may indicate opportunity to intervene with specific inhibitors of COX-2 in
      carcinoma of the cervix.

PMID- 11286826
TI  - Patterns of failure after induction chemotherapy and radiotherapy for
      locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital
      experience.
AB  - PURPOSE: Our center contributed 183 patients to the Asian-Oceanian Clinical
      Oncology Association (AOCOA) multicenter randomized trial comparing induction
      chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with
      locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a
      preliminary report no difference in terms of overall survival or relapse-free
      survival was found between the 2 treatment arms. To study the long-term outcome
      and patterns of failure after CT for NPC, we analyzed our own center data for
      which a uniform radiation treatment protocol was adopted and a longer follow-up
      time was available. METHODS AND MATERIALS: Between September 1989 and August
      1993, a total of 183 patients were recruited into the AOCOA randomized study from
      our center. Patients with newly diagnosed NPC of Ho's T3 disease, N2-N3 disease,
      or with neck node size of at least 3 cm were eligible. Stratification was made
      according to the nodal size (< or = 3 cm, >3- 6 cm, > 6 cm). Patients were
      randomized to receive 2-3 cycles of CT with cisplatin 60 mg/m(2) and epirubicin
      110 mg/m(2) D1 followed by RT or RT alone. Four patients were excluded from the
      current analysis (2 died before treatment, 2 received treatment elsewhere). The
      remaining 179 patients were randomized to the two treatment arms, with 92 to the
      CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all
      patients completed radiation treatment. Overall survival (OAS), relapse-free
      survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival
      (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan-
      Meier method and significance of survival curve differences calculated using log-
      rank test. Analysis was performed based on the intent-to-treat. RESULTS: The
      median follow-up was 70 months. At the time of analysis, 50% of patients in the
      CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the
      RT arm had died of the disease. The median RFS was 83 months in the CT arm and 37
      months in the RT arm. The median OAS has not yet been reached for both arms. No
      significant differences were found for the various endpoints, although there was
      a trend suggesting better nodal control in the CT arm. The 5-year rates for the
      various endpoints in the CT arm vs. the RT arm were: 53% vs. 42% for RFS (p =
      0.13), 70% vs. 67% for OAS (p = 0.68), 80% vs. 77% for LRFS (p = 0.73), 89% vs.
      80% for NRFS (p = 0.079), and 70% vs. 68% for DMFS (p = 0.59). There was also no
      significant difference in the patterns of failure between both arms: in the CT
      arm, 28% of failures were local only, 13% regional only, 4% locoregional, 44%
      distant, and 11% mixed locoregional and distant. In the RT arm, 23% of failures
      were local only, 13% regional only, 11% locoregional, 43% distant, and 9% mixed
      locoregional and distant. CONCLUSION: Induction chemotherapy with the regimen
      used in the current study did not improve the treatment outcome or alter the
      failure patterns in patients with locoregionally advanced NPC, although there was
      a trend suggesting better nodal control in the combined modality arm. Alternative
      strategies of combining chemotherapy and radiotherapy should be tested and
      employed instead.

PMID- 11286827
TI  - Failure of a 3D conformal boost to improve radiotherapy for nasopharyngeal
      carcinoma.
AB  - PURPOSE: To determine whether the use of 3-dimensional (3D) boost for patients
      with nasopharynx cancer improves local control and reduces the risk of long-term
      complications. METHODS AND MATERIALS: From 1988 to 1998, 68 patients with
      nasopharynx cancer received conventional external beam therapy followed by a 3D
      boost. Disease characteristics of treated patients were as follows: WHO I
      histology 7%, WHO II 62%, WHO III 31%, clinical AJCC stage T1--2 45%, T3--4 55%,
      N0--1 63%, N2--3 37%, M0 100%. The median radiation dose was 70 Gy (68--75.6 Gy).
      Thirty-five patients (52%) received cisplatin-based chemotherapy. The median
      follow-up of surviving patients was 42 months (12--118 months). RESULTS: Five
      year actuarial local control was 77%, regional control was 97%, progression-free
      survival was 56%, and overall survival was 58%. Stage was the only identifiable
      prognostic factor: 5-year progression-free survival was 65% for Stages I--III vs.
      40% for Stage IV (p = 0.01). The incidence of Grade 3-4 complications was 25% and
      included hearing loss, trismus, dysphagia, chronic sinusitis, and cranial
      neuropathy. These results are comparable to outcomes reported with conventional
      radiation techniques for similarly staged patients. CONCLUSION: The lack of a
      major benefit with the 3D boost may be related to the fact that CT planning was
      only used for a fraction of the total dose. We are now using intensity modulated
      radiation therapy to deliver the entire course of radiation. Intensity modulated
      radiation therapy achieves better conformal distributions than conventional 3D
      planning, allowing dose escalation and increased normal tissue sparing.

PMID- 11286828
TI  - Carcinoma-in-situ of the glottic larynx: results of treatment with radiation
      therapy.
AB  - PURPOSE: Carcinoma-in-situ (CIS) of the vocal cords frequently progresses to
      invasive disease if untreated. Treatment approaches include vocal cord stripping,
      radiation therapy (RT), and laser excision. The purpose of this analysis was to
      assess the efficacy and safety of a standard RT regimen in the treatment of this
      condition. METHODS AND MATERIALS: Between January 1980 and December 1994, 67
      patients (52 men, 15 women; median age, 65 years) with glottic CIS were treated
      with RT. The standard RT regimen was 51 Gy in 20 fractions given over 4 weeks
      (99% of patients). Prior to receiving RT, 21 patients (31%) had undergone 1 or 2
      vocal cord stripping procedures, and 1 had been treated with laser. RESULTS: With
      a median follow-up of 6.5 years, 1 patient developed invasive glottic cancer,
      giving a 5-year actuarial local control rate of 98%. This patient recurred 14
      months after treatment and was salvaged with laryngectomy. He is currently free
      of disease 2 years after surgery. There were no serious acute or late treatment
      complications. Sixteen patients (24%) developed subsequent malignancies, 8 of
      these being in the upper aerodigestive tract, although none were in the radiation
      field. CONCLUSIONS: Moderate-dose radiation therapy is an effective treatment for
      glottic CIS. It is well tolerated, produces no serious acute or long-term side
      effects, with an excellent cure rate.

PMID- 11286829
TI  - Efficacy of radiotherapy for giant cell tumor of bone: given either
      postoperatively or as sole treatment.
AB  - PURPOSE: The aim of this paper is to evaluate efficacy of radiotherapy for giant
      cell tumor of bone given either postoperatively or as sole treatment, and to
      assess prognostic factors for treatment outcome. METHODS AND MATERIALS: The study
      includes 37 patients. In 9 cases, soft tissue involvement was noted. Nonradical
      operation followed by radiotherapy was given to 23 patients, and 14 patients
      received irradiation only. Total dose of 39--64 Gy was delivered. The average
      follow-up was 5 years. Probability of local tumor control (LTC) depending on the
      treatment strategy was calculated, and prognostic factors were assessed. RESULTS:
      LTC was noted in 31 cases. Ten-year LTC for surgery with irradiation was 83% and
      69% for radiotherapy alone; however, this difference was not statistically
      significant. For tumors smaller than 4 cm LTC probability was above 90%, and it
      decreased to less than 60% for tumors larger than 8.5 cm. No dose-response
      relationship has been found. In 7 cases, late normal tissue effect occurred.
      CONCLUSIONS: Giant cell tumors of bone can be considered as radiosensitive and
      radiotherapy with total dose of 40--45 Gy seems to be an effective sole treatment
      especially for tumors smaller than 4 cm in diameter. For larger tumors, surgery
      combined with postoperative radiotherapy should be considered.

PMID- 11286830
TI  - Megavoltage radiotherapy for aneurysmal bone cysts.
AB  - PURPOSE: An aneurysmal bone cyst (ABC) is a rapidly expansile and destructive
      benign tumor of bone that is usually treated by curettage and bone graft, with or
      without adjuvant treatment. For recurrent tumors, or tumors for which surgery
      would result in significant functional morbidity, does radiotherapy (RT) provide
      a safe and effective alternative for local control? PATIENTS AND METHODS: Nine
      patients with histologically diagnosed aneurysmal bone cysts without other
      associated benign or malignant tumors were treated at the University of Florida
      with megavoltage RT between February 1964 and June 1992. The patients received
      local radiotherapy doses between 20 and 60 Gy, with 6 patients receiving 26--30
      Gy. In 6 patients the diagnosis was made by biopsy alone; 3 underwent
      intralesional curettage before RT. Minimum follow-up was 20 months; 7 of 9
      patients (77%) had follow-up greater than 11 years. RESULTS: No patient
      experienced a local recurrence (median follow-up, 17 years). One patient required
      stabilization of the cervical spine 10 months after RT because of dorsal kyphosis
      from vertebral body collapse. No other significant side effects were experienced,
      and no patients developed secondary malignancies. Four patients were lost to
      follow-up: at 20 months, 11.5 years, 17 years, and 20 years after the initiation
      of treatment, none with any evidence of local recurrence. All of the patients who
      had significant pain before RT had relief of their symptoms within 2 weeks of
      completion of therapy. CONCLUSIONS: Using modern-day RT, patients with recurrent
      or inoperable aneurysmal bone cysts can be treated effectively (with minimal
      toxicity) using a prescribed tumor dose of 26--30 Gy.

PMID- 11286831
TI  - CT and (18)F-deoxyglucose (FDG) image fusion for optimization of conformal
      radiotherapy of lung cancers.
AB  - PURPOSE: To validate a computed tomography (CT) and (18)F-deoxyglucose (FDG)
      image fusion procedure and to evaluate its usefulness to facilitate target
      definition and treatment planning in three-dimensional conformal radiation
      therapy (3D-CRT) for non-small-cell lung cancer. METHODS AND MATERIALS: Twelve
      patients were assessed by CT and FDG-coincidence mode dual-head gamma camera
      (CDET) before radiotherapy. The patients were placed in a similar position during
      CT and FDG-CDET. Matching was achieved by minimizing the cost function by 3D
      translation and rotation between four landmarks drawn on the patient's skin.
      Virtual simulation was performed from image fusion and estimated dose-volume
      histograms (DVH) were calculated. RESULTS: Quantitative analysis indicated that
      the matching error was < 5 mm. Fusion of anatomic and metabolic data corrected
      staging of lymph nodes (N) for 4 patients and staging of metastases for 1
      patient. In these 5 patients, DVH revealed that the lung volume irradiated at 20
      Gy (Vl(20)) was decreased by an average of 22.8%, and tumor volume irradiated at
      the 95% isodose (V(95)) was increased by 22% and 8% for 2 patients, respectively,
      and was decreased by an average of 59% for 3 patients after fusion. No difference
      in terms of Vl(20) and V(95) was observed for the other 7 patients. CONCLUSION:
      We have validated CT and FDG-CDET lung image fusion to facilitate determination
      of lung cancer volumes, which improved the accuracy of 3D-CRT.

PMID- 11286832
TI  - Prognostic significance of lymphocyte infiltration following preoperative
      chemoradiotherapy and hyperthermia for esophageal cancer.
AB  - PURPOSE: Lymphocyte infiltration (LI) around cancerous lesions is an important
      immune response. The purpose of this study is to evaluate the prognostic
      significance of LI after preoperative treatment for esophageal cancer. METHODS
      AND MATERIALS: Preoperative chemoradiotherapy (CR therapy), either bleomycin 30
      mg or cisplatin 120 mg/m(2) plus radiation 30 Gy, was performed on 51 cases with
      esophageal cancer, while hyperthermo-chemoradiotherapy (HCR therapy) was also
      indicated in 71 cases. Using resected specimens, both the histopathologic
      effectiveness and degree of LI to cancerous lesions were evaluated. RESULTS: The
      incidences of the cases in which preoperative treatment was effective were 56%
      and 92.3% in LI (-) and LI (++) group (p < 0.05). The presence of LI resulted in
      favorable prognosis; the 5-year survival rates of LI (++) and LI (+) patients
      were 75.5% and 46.1%, both of which were significantly better than LI (-) (27.8%,
      p < 0.05 and p < 0.01, respectively). Especially among cases whose preoperative
      treatment was moderately effective, a multivariate analysis revealed LI to be a
      favorable prognostic factor independent of other clinicopathologic factors (p =
      0.0171). Regarding the preoperative treatment, the incidence of LI (++) was
      higher in the HCR group (16.9%) than in the CR group (2.0%, p < 0.01).
      CONCLUSIONS: LI appears to be a prognostic predictor after preoperative CR
      therapy while, in addition, simultaneous hyperthermia may stimulate LI in cases
      with esophageal cancer.

PMID- 11286833
TI  - Intraoperative irradiation for locally recurrent colorectal cancer in previously
      irradiated patients.
AB  - PURPOSE: Information in the literature regarding salvage treatment for patients
      with locally recurrent colorectal cancer who have previously been treated with
      high or moderate dose external beam irradiation (EBRT) is scarce. A retrospective
      review was therefore performed in our institution to determine disease control,
      survival, and tolerance in patients treated aggressively with surgical resection
      and intraoperative electron irradiation (IOERT) +/- additional EBRT and
      chemotherapy. METHODS AND MATERIALS: From 1981 through 1994, 51 previously
      irradiated patients with recurrent locally advanced colorectal cancer without
      evidence of distant metastatic disease were treated at Mayo Clinic Rochester with
      surgical resection and IOERT +/- additional EBRT. An attempt was made to achieve
      a gross total resection before IOERT if it could be safely accomplished. The
      median IOERT dose was 20 Gy (range, 10--30 Gy). Thirty-seven patients received
      additional EBRT either pre- or postoperatively with doses ranging from 5 to 50.4
      Gy (median 25.2 Gy). Twenty patients received 5-fluorouracil +/- leucovorin
      during EBRT. Three patients received additional cycles of 5-fluorouracil +/-
      leucovorin as maintenance chemotherapy. RESULTS: Thirty males and 21 females with
      a median age of 55 years (range 31--73 years) were treated. Thirty-four patients
      have died; the median follow-up in surviving patients is 21 months. The median, 2
      yr, and 5-yr actuarial overall survivals are 23 months, 48% and 12%,
      respectively. The 2-yr actuarial central control (within IOERT field) is 72%.
      Local control at 2 years has been maintained in 60% of patients. There is a trend
      toward improved local control in patients who received > or =30 Gy EBRT in
      addition to IOERT as compared to those who received no EBRT or <30 Gy with 2-yr
      local control rates of 81% vs. 54%. Distant metastatic disease has developed in
      25 patients, and the actuarial rate of distant progression at 2 and 4 years is
      56% and 76%, respectively. Peripheral neuropathy was the main IOERT-related
      toxicity; 16 (32%) patients developed neuropathies (7 mild, 5 moderate, 4
      severe). Ureteral narrowing or obstruction occurred in seven patients. All but
      one patient with neuropathy or ureter fibrosis received IOERT doses > or =20 Gy.
      CONCLUSION: Long-term local control can be obtained in a substantial proportion
      of patients with aggressive combined modality therapy, but long-term survival is
      poor due to the high rate of distant metastasis. Re-irradiation with EBRT in
      addition to IOERT appears to improve local control. Strategies to improve
      survival in these poor-risk patients may include the more routine use of
      conventional systemic chemotherapy or the addition of novel systemic therapies.

PMID- 11286835
TI  - Radioimmunoguided imaging of prostate cancer foci with histopathological
      correlation.
AB  - PURPOSE: We have previously presented a technique that fuses ProstaScint and
      pelvic CT images for the purpose of designing brachytherapy that targets areas at
      high risk for treatment failure. We now correlate areas of increased intensity
      seen on ProstaScint-CT fusion images to biopsy results in a series of 7 patients
      to evaluate the accuracy of this technique in localizing intraprostatic disease.
      METHODS AND MATERIALS: The 7 patients included in this study were evaluated
      between June 1998 and March 29, 1999 at Metrohealth Medical Center and University
      Hospitals of Cleveland in Cleveland, Ohio. ProstaScint and CT scans of each
      patient were obtained before transperineal biopsy and seed implantation. Each
      patient's prostate gland was biopsied at 12 separate sites determined
      independently of Prostascint-CT scan results. RESULTS: When correlated with
      biopsy results, our method yielded an overall accuracy of 80%: with a sensitivity
      of 79%, a specificity of 80%, a positive predictive value of 68%, and a negative
      predictive value of 88%. CONCLUSION: The image fusion of the pelvic CT scan and
      ProstaScint scan helped identify foci of adenocarcinoma within the prostate that
      correlated well with biopsy results. These data may be useful to escalate doses
      in regions containing tumor by either high-dose rate or low-dose rate
      brachytherapy, as well as by external beam techniques such as intensity modulated
      radiotherapy (IMRT).

PMID- 11286834
TI  - Paclitaxel and concurrent radiation for locally advanced pancreatic cancer.
AB  - PURPOSE: To determine the activity and toxicity of paclitaxel and concurrent
      radiation for pancreatic cancer. METHODS AND MATERIALS: Forty-four patients with
      locally unresectable pancreatic cancer were studied. Patients received
      paclitaxel, 50 mg/m(2) by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22
      and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in
      1.80 Gy fractions, for 28 treatments. RESULTS: Nausea and vomiting were the most
      common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4
      hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable
      patients, the overall response rate was 26%. The median survival was 8 months,
      and the 1-year survival was 30%. CONCLUSION: Concurrent paclitaxel and radiation
      demonstrate local-regional activity in pancreatic cancer. Future investigations
      combining paclitaxel with other local-regional and systemic treatments are
      warranted.

PMID- 11286836
TI  - Chemical disease-free survival in localized carcinoma of prostate treated with
      external beam irradiation: comparison of American Society of Therapeutic
      Radiology and Oncology Consensus or 1 ng/mL as endpoint.
AB  - PURPOSE: To compare postirradiation biochemical disease-free survival using the
      American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus or
      elevation of postirradiation prostate-specific antigen (PSA) level beyond 1 ng/mL
      as an endpoint and correlate chemical failure with subsequent appearance of
      clinically detected local recurrence or distant metastasis. METHODS AND
      MATERIALS: Records of 466 patients with histologically confirmed adenocarcinoma
      of the prostate treated with irradiation alone between January 1987 and December
      1995 were analyzed; 339 patients were treated with bilateral 120 degrees arc
      rotation and, starting in 1992, 117 with three-dimensional conformal irradiation.
      Doses were 68--77 Gy in 1.8 to 2 Gy daily fractions. Minimum follow-up is 4 years
      (mean, 5.5 years; maximum, 9.6 years). A chemical failure was recorded using the
      ASTRO Consensus or when postirradiation PSA level exceeded 1 ng/mL at any time.
      Clinical failures were determined by rectal examination, radiographic studies,
      and, when clinically indicated, biopsy. RESULTS: Six-year chemical disease-free
      survival rates using the ASTRO Consensus according to pretreatment PSA level for
      T1 tumors were: < or = 4 ng/mL, 100%; 4.1--20 ng/mL, 80%; and > 20 ng/mL, 50%.
      For T2 tumors the rates were: < or = 4 ng/mL, 91%; 4.1--10 ng/mL, 81%; 10.1--20
      ng/mL, 55%; 20.1--40 ng/mL, 63%; and > 40 ng/mL, 46%. When postirradiation PSA
      levels higher than 1 ng/mL were used, the corresponding 6-year chemical disease
      free survival rates for T1 tumors were 92% for pretreatment PSA levels of < or =
      4 ng/mL, 58--60% for levels of 4.1--20 ng/mL, and 30% for levels > 20 ng/mL. For
      T2 tumors, the 6-year chemical disease-free survival rates were 78% in patients
      with pretreatment PSA levels of 4--10 ng/mL, 45% for 10.1--40 ng/mL, and 25% for
      > 40 ng/mL. Of 167 patients with T1 tumors, 30 (18%) developed a chemical
      failure, 97% within 5 years from completion of radiation therapy; no patient has
      developed a local recurrence or distant metastasis. In patients with T2 tumors,
      overall 45 of 236 (19%) had chemical failure, 94% within 5 years of completion of
      radiation therapy; 4% have developed a local recurrence, and 10%, distant
      metastasis. In patients with T3 tumors, overall, 24 of 65 (37%) developed a
      chemical failure, 100% within 3.5 years from completion of radiation therapy; 4%
      of these patients developed a local recurrence within 2 years, and 12% developed
      distant metastasis within 4 years of completion of irradiation. The average time
      to clinical appearance of local recurrence or distant metastasis after a chemical
      failure was detected was 5 years and 3 years, respectively. CONCLUSION: There was
      a close correlation between the postirradiation nadir PSA and subsequent
      development of a chemical failure. Except for patients with T1 tumors and
      pretreatment PSA of 4.1--20 ng/mL, there is good agreement in 6-year chemical
      disease-free survival using the ASTRO Consensus or PSA elevations above 1 ng/mL
      as an endpoint. Although the ASTRO Consensus tends to give a higher percentage of
      chemical disease-free survival in most groups, the differences with longer follow
      up are not statistically significant (p > 0.05). It is important to follow these
      patients for at least 10 years to better assess the significance of and the
      relationship between chemical and clinical failures.

PMID- 11286837
TI  - Retrospective stratification of a consecutive cohort of prostate cancer patients
      treated with a combined regimen of external-beam radiotherapy and brachytherapy.
AB  - PURPOSE: The evaluation of clinical variables that influence biochemical relapse
      free survival in a cohort of patients treated by combined radiotherapy over a
      fixed interval. METHODS AND MATERIALS: Three hundred forty-eight patients
      diagnosed with clinical Stage T1--T3a prostate cancer were treated with a course
      of (103)Pd or (125)I brachytherapy followed by a limited course of external beam
      radiation formed the basis for study. All censored patients had a minimum 2-year
      follow-up. Biochemical relapse-free survival (BRFS) was estimated using a
      modified American Society for Therapeutic Radiology and Oncology consensus
      definition. Discrete "risk groups" were developed based on BRFS as influenced by
      pretreatment parameters. RESULTS: Significant risk factors contributing to
      biochemical failure were serum prostate-specific antigen (PSA) greater than 20
      ng/mL, Gleason sum of 7 or greater, or clinical stage T2c or greater. Five-year
      biochemical control for those exhibiting no risk factor was 88%; one risk factor,
      75%; two or more risk factors, 51%. The differences in BRFS among all three risk
      groups were statistically significant. Outcomes for patients presenting with PSA
      10 to 20 ng/mL, but otherwise low-risk disease, fared no differently from those
      low risk patients presenting with PSA less than 10 ng/mL. CONCLUSIONS: Combined
      radiotherapy with (103)Pd or (125)I followed by external beam radiotherapy
      achieves a high rate of biochemical and clinical control in patients with low- to
      intermediate-risk clinically organ confined disease.

PMID- 11286838
TI  - Apoptosis, proliferation and p53, cyclin D1, and retinoblastoma gene expression
      in relation to radiation response in transitional cell carcinoma of the bladder.
AB  - PURPOSE: To determine whether the apoptotic index, the Ki67 index, and the
      expression of the p53, cyclin D1, and retinoblastoma genes correlate with local
      control, overall survival, and time to distant metastases in invasive bladder
      cancer treated with external beam radiation. METHODS AND MATERIALS: Paraffin
      embedded pretreatment biopsies from 83 patients with invasive transitional cell
      carcinoma of the bladder were scored morphologically for apoptosis and
      immunohistochemically for Ki67, p53, cyclin D1, and retinoblastoma gene
      expression. Survival analysis methods were used to assess overall survival, local
      control, and freedom from distant metastases. A multiple proportional hazard (PH)
      regression analysis was performed to study the prognostic value of the
      abovementioned biologic parameters (all divided into two categories, except Ki67)
      in addition to classical prognostic factors such as T stage, histologic grade,
      multifocality of the tumor, and completeness of transurethral resection. All
      patients were treated with external beam radiation as sole treatment. Median
      follow-up for the 19 patients still living was 7.5 years. RESULTS: Apoptotic
      index varied from 0% to 3.4% with a mean of 0.8% and a median of 0.6%. Ki67 index
      varied from 0% to 60% with a mean of 14% and a median of 12%. P53 protein was
      detectable in 61% of the tumors. Overexpression of cyclin D1 was observed in 39%
      of the tumors and loss of retinoblastoma protein in 23% of the tumors. High Ki67
      index was found to be significantly associated with p53 expression (p = 0.04) and
      cyclin D1 overexpression (p = 0.023). Cyclin D1 overexpression was found more
      often in Rb-positive tumors than in Rb-negative tumors (p = 0.006). Other
      associations between the markers are less clear. Biologic markers were not
      correlated with T stage or grade. In the PH analysis local control was found to
      be significantly better for tumors with wild-type p53 (p = 0.028). Also, tumors
      with an apoptotic index above the median value (0.6%) had a significantly better
      local control rate (p = 0.035). Ki67 index (p = 0.35), retinoblastoma gene
      expression (p = 0.30) and cyclin D1 overexpression (p = 0.61) were not found to
      have an additional predictive value regarding local tumor control. None of the
      tested biologic parameters were found to be associated with overall survival.
      Time to distant metastases was significantly shorter for tumors with high Ki67
      index (p = 0.01) and tumors with an apoptotic index less than median (p = 0.009).
      CONCLUSIONS: The results of our study provide evidence for a prognostic value of
      p53 expression and apoptotic index with respect to the radiation response in
      bladder cancer in addition to more conventional prognosticators. The value of
      these parameters as a predictive assay for radiation response warrants
      confirmation in larger and prospective studies.

PMID- 11286839
TI  - Aichi Cancer Center 10-year experience with conservative breast treatment of
      early breast cancer: retrospective analysis regarding failure patterns and
      factors influencing local control.
AB  - PURPOSE: We analyzed the clinical results of conservative breast therapy in our
      institute to determine the risk factors influencing local and distant disease
      recurrence. METHODS AND MATERIALS: From 1989 to 1997, 301 breasts of 295 women
      with early breast cancer were treated with conservative surgery and adjuvant
      radiotherapy. There were 212 incidences of Stage I breast cancer, and 89 of Stage
      II. Patients were routinely treated with local resection, axillar dissection, and
      46--50 Gy irradiation given in 23--25 fractions. Some also received a radiation
      boost to the tumor bed. RESULTS: The 5-/8-year overall survival, disease-free
      survival, and local control rates were 93.2/91.5%, 86.0/80.6%, and 95.1/92.5%,
      respectively. Using both univariate and multivariate analyses, tumor volume,
      estrogen receptor status, and age < 40 years were significant prognostic factors
      for disease-free survival. Both age < 40 years and surgical method had a strong
      effect on local control by uni- and multivariate analysis. Surgical margin status
      was a significant prognostic factor for local control at the univariate level (p
      < 0.0001), though it had only borderline significance at the multivariate level
      (p = 0.08). No patient experienced severe morbidity due to radiotherapy.
      CONCLUSION: The results obtained are comparable to previously reported data.
      Although the follow-up period was too short to draw definite conclusions about
      long-term outcomes, the outcome from conservative breast treatment was
      acceptable.

PMID- 11286840
TI  - Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is
      feasible and effective except for inflammatory disease.
AB  - PURPOSE: To investigate the feasibility and effectiveness of
      radiochemothermotherapy (triple-modality therapy) in patients with inoperable
      recurrent breast cancer. PATIENTS AND METHODS: Patients with inoperable recurrent
      lesions, World Health Organization (WHO) performance status of 2 or greater, life
      expectancy of more than 3 months, adequate bone marrow, hepatic and renal
      function were eligible for this Phase I/II study. Conventionally fractionated or
      hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia
      (HT) combined with chemotherapy (CT; epirubicin 20 mg/m(2), ifosfamide 1.5
      g/m(2)) was applied within 30 min after RT. RESULTS: Twenty-five patients, all
      heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy.
      The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone
      marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The
      overall response rate was 80% with a complete response (CR) rate of 44%. Response
      rates in patients with noninflammatory disease (n = 14; CR 10 patients, partial
      response [PR] 3 patients) were far better than in patients with inflammatory
      disease (n = 11; CR 1 patient, PR 6 patients). CONCLUSIONS: In patients with
      recurrent breast cancer, triple-modality therapy is feasible with acceptable
      toxicity. High remission rates can be achieved in noninflammatory disease,
      however, local control is limited to a few months. Whether the addition of
      chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an
      open question.

PMID- 11286841
TI  - The risk of second malignant tumors and its consequences for the overall survival
      of Hodgkin's disease patients and for the choice of their treatment at
      presentation: analysis of a series of 1524 cases consecutively treated at the
      Florence University Hospital.
AB  - PURPOSE: To quantify the incidence of second malignant tumors (SMT) as a whole
      and that of second "solid" tumors (SST) and leukemia (L) in a large series of
      1524 Hodgkin's disease (HD) patients (pts) treated at the Florence University
      Hospital (UFH); to define the clinical and therapeutic features possibly related
      with SMT occurrence; to evaluate the consequences of SMT for the overall survival
      of the series studied and for the choice of the treatment of HD at presentation.
      METHODS AND MATERIALS: From 1960 to 1991, 1524 pts with HD, Clinical Stage (CS) I
      -IV have been treated at the UFH. Overall treatment consisted of radiation alone
      (RT, 36%), chemotherapy alone (CHT, 21%), or both (RT + CHT, 43%). The cumulative
      probability (CP) of SMT, SST, and L was calculated for the whole series and for
      the different clinical and therapeutic subgroups, and the results compared with
      uni- and multivariate analysis ("internal" comparison, IC). Standardized
      incidence ratios (SIR) for different SMT types (estimated on the basis of gender,
      age, period specific incidence rates of the general population) have been also
      calculated ("external" comparison, EC). The impact of the SMT-related mortality
      on the survival of the entire series has been estimated. RESULTS: A 14.9% 20-year
      CP of SMT was registered, along with a SIR of 2.04 (95% confidence interval [CI]:
      1.2--2.5). Both IC and EC showed a statistically significant relationship between
      L incidence and treatment with CHT, alone or in combination with RT. A
      significant excess of breast cancers has been observed in RT-treated patients
      with longer follow-up (SIR, 2.9); an excess of other common SST (lung, non
      Hodgkin's lymphomas) is evident in pts treated with either RT, RT + CHT, or CHT.
      The actuarial long-term survival of the series would have been better of about
      3%, in absence of the SMT mortality possibly due to HD treatment, which is almost
      equally divided between patients treated with RT alone, CHT alone, and RT + CHT.
      CONCLUSIONS: SMT represent an important late event in HD long-term survivors. The
      relationship between L and treatment with CHT seems to be the most clearly
      defined. The effect of SMT on the survival of the entire series, although not
      negligible, does not seem to justify by itself substantial alterations in the
      current standards for the treatment of HD at presentation.

PMID- 11286842
TI  - Transient enlargement of contrast uptake on MRI after linear accelerator (linac)
      stereotactic radiosurgery for brain metastases.
AB  - PURPOSE/OBJECTIVE: With the increasing number of patients successfully treated
      with stereotactic radiosurgery for brain metastases, decision making after
      therapy based on follow-up imaging findings becomes more and more important.
      Magnetic resonance imaging (MRI) is the most sensitive means for follow-up
      studies. The objective of this study was to investigate the treatment outcome of
      our radiosurgery program and to describe the response of brain metastases to
      contrast-enhanced MRI after linear accelerator (linac) stereotactic radiosurgery
      and identify factors to distinguish among local control and local failure.
      METHODS AND MATERIALS: Using serial MRI, we followed the course of 87 brain
      metastases in 48 consecutive patients treated between September 1996 and November
      1997 with linac-based radiosurgery with 15-MV photons. Treatment planning was
      performed on an MR data cube. For spherical metastases, radiosurgery was
      delivered using a 9 noncoplanar arc technique with circular-shaped collimators.
      For irregularly shaped targets, radiosurgery was delivered using a manually
      driven multi-leaf collimator with a leaf width of 1.5 mm projected to the
      isocenter. Median radiosurgery dose was 20 Gy prescribed to the 80% isodose.
      Together with whole brain radiotherapy (20 x 2 Gy, 5/w), a median radiosurgical
      dose of 15 Gy was delivered. Median follow-up was 8 (range 2--36) months. Factors
      influencing local control and survival rates were analyzed with respect to MRI
      response, and Kaplan-Meier curves were calculated. RESULTS: Actuarial local tumor
      control was 91% at one and two years. Patient survival at one and two years was
      30% and 18%. Median survival was 9 months. During follow-up in 70 (81%) of the 87
      treated metastases, the contrast-enhancing volumes on T1W images were stable or
      disappeared partly or completely. A transient enlargement of contrast-enhancing
      volumes was observed in 11 (12%) of the 87 lesions treated, while a progressive
      enlargement due to local treatment failure was observed in 6 (7%) of the 87
      treated metastases. Younger age, early contrast onset after radiosurgery, and
      previous chemotherapy were associated with this transient enlargement of contrast
      enhancing lesion volume. CONCLUSIONS: Linac-based radiosurgery is an effective,
      noninvasive, and safe treatment option for patients with brain metastases. A
      marked enlargement of the contrast-enhancing volume on T(1)-weighted MR images
      after radiosurgery is a sensitive predictor for, but not equivalent with, local
      failure. In as many as two-thirds of the cases with contrast enlargement in MRI
      follow-up, the contrast enlargement is transient with no need for further
      treatment. While some MRI findings are more likely if transient enlargement is
      present, a clear decision cannot be made based on MRI, and ultimately the
      clinical status dictates further action.

PMID- 11286843
TI  - Equivalence of hyperfractionated and continuous brachytherapy in a rat tumor
      model and remarkable effectiveness when preceded by external irradiation.
AB  - PURPOSE: In clinical brachytherapy, there is a tendency to replace continuous low
      dose-rate (LDR) irradiation by either single-dose or fractionated high-dose-rate
      (HDR) irradiation. In this study, the equivalence of LDR treatments and
      fractionated HDR (2 fractions/day) or pulsed-dose-rate (PDR, 4 fractions/day)
      schedules in terms of tumor cure was investigated in an experimental tumor model.
      METHODS AND MATERIALS: Tumors (rat rhabdomyosarcoma R1M) were grown s.c. in the
      flank of rats and implanted with 4 catheters guided by a template. All
      interstitial radiation treatment (IRT) schedules were given in the same geometry.
      HDR was given using an (192)Ir single-stepping source. To investigate small
      fraction sizes, part of the fractionated HDR and PDR schedules were applied after
      an external irradiation (ERT) top-up dose. The endpoint was the probability of
      tumor control at 150 days after treatment. Cell survival was estimated by
      excision assay. RESULTS: Although there was no fractionation effect for
      fractionated HDR given in 1 or 2 fractions per day, TCD(50)-values were
      substantially lower than that for LDR. A PDR schedule with an interfraction
      interval of 3 h (4 fractions/day), however, was equivalent to LDR. The
      combination of ERT and IRT resulted in a remarkably increased tumor control
      probability in all top-up regimens, but no difference was found between 2 or 4
      fractions/day. Catheter implantation alone decreased the TCD(50) for single-dose
      ERT already by 17.4 Gy. Cell viability assessed at 24 h after treatment
      demonstrated an increased effectiveness of interstitial treatment, but, after 10
      Gy ERT followed by 10 Gy IRT (24-h interval), it was not less than that
      calculated for the combined effect of these treatments given separately.
      CONCLUSION: In full fractionation schedules employing large fractions and long
      intervals, the sparing effect of sublethal damage repair may be significantly
      counteracted by reoxygenation. During 3-h intervals, however, repair may be
      largely completed with only partial reoxygenation causing PDR schedules to be
      less effective than fractionated HDR, and equivalent to LDR. Brachytherapy with
      clinically sized fractions after a large external top-up dose showed a remarkable
      increase in tumor control rate with no effect of fractionation (up to 4
      fractions/day), which could not be fully explained by differences in dose
      distribution or in the cell viability assessed after treatment. This suggests a
      longer lasting effect on cell survival or radiosensitivity associated with
      catheter implantation shortly after the top-up dose.

PMID- 11286844
TI  - Radiobiologic significance of apoptosis and micronucleation in quiescent cells
      within solid tumors following gamma-ray irradiation.
AB  - PURPOSE: To determine the frequency of apoptosis in quiescent (Q) cells within
      solid tumors following gamma-ray irradiation, using four different tumor cell
      lines. In addition, to assess the significance of detecting apoptosis in these
      cell lines. METHODS AND MATERIALS: C3H/He mice bearing SCC VII or FM3A tumors,
      Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5
      bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic
      pumps to label all proliferating (P) cells. The mice then received gamma-ray
      irradiation at a dose of 4--25 Gy while alive or after tumor clamping.
      Immediately after irradiation, the tumors were excised, minced, and trypsinized.
      The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a
      cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU
      labeling (= Q cells) was determined using immunofluorescence staining for BrdU.
      Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same
      manner were fixed. The apoptosis frequency in Q cells was also determined with
      immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P
      + Q) tumor cells were determined from the tumors that were not pretreated with
      BrdU. RESULTS: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable
      relationships between MN frequency and surviving fraction (SF). However, fewer
      micronuclei were induced in EL4 cells than the other cell lines. In contrast, a
      comparatively close relationship between apoptosis frequency and SF was found in
      total cells of EL4 cell line. Less apoptosis was observed in the other cell
      lines. Quiescent tumor cells exhibited significantly lower values of MN and
      apoptosis frequency probably due to their large hypoxic fraction, similar to
      total tumor cells on clamped irradiation. CONCLUSION: gamma-ray irradiation
      induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis
      was marked in EL4 cells compared with the other cell lines. Our method for
      detecting the Q cell response to gamma-ray irradiation using P cell labeling with
      BrdU and the MN frequency assay was also applicable to apoptosis detection assay.

PMID- 11286845
TI  - The role of intracellular Ca(2+) in apoptosis induced by hyperthermia and its
      enhancement by verapamil in U937 cells.
AB  - PURPOSE: The relationship between apoptosis induced by 42 degrees C and 44
      degrees C hyperthermia alone or in combination with verapamil and changes in
      intracellular Ca(2+) concentration ([Ca(2+)]i) was investigated in U937 cells.
      METHODS: Apoptosis induced by hyperthermia was assessed according to DNA
      fragmentation, nuclear morphologic changes, and expression of phosphatidylserine
      on the outside plasma cell membrane. These changes were measured by flow
      cytometry. The [Ca(2+)]i of individual cells after hyperthermia was monitored by
      a digital image-analyzing technique using Fura-2. RESULTS: Hyperthermia-induced
      apoptosis reached a plateau after 6 h and was found to be both time and
      temperature-dependent. DNA fragmentation was maximum at 44 degrees C after 30
      min. Verapamil enhanced the apoptosis induced by 42 degrees C and 44 degrees C
      hyperthermia in normal cells and by 44 degrees C hyperthermia in thermotolerant
      cells. The number of cells containing higher [Ca(2+)]i (more than 200 nM) was
      significantly increased by hyperthermia and further elevated by the addition of
      verapamil in both normal and thermotolerant cells. Apoptosis induced by
      hyperthermia was markedly decreased by an intracellular Ca(2+) chelator, BAPTA
      AM, in a dose-dependent manner. CONCLUSION: These results indicate that [Ca(2+)]i
      increase plays a crucial role in apoptosis induced by hyperthermia and the
      combined treatment with verapamil in normal and thermotolerant U937 cells.
      Furthermore, hyperthermia-combined drug therapy has potential significance in
      cancer therapy.

PMID- 11286846
TI  - Effects of Motexafin gadolinium on tumor metabolism and radiation sensitivity.
AB  - PURPOSE: Experiments were undertaken to determine if metabolic changes induced by
      Motexafin gadolinium (Gd-Tex(+2), XCYTRIN) predict time intervals between drug
      and radiation wherein there is enhancement of radiation efficacy. METHODS AND
      MATERIALS: We evaluated the effect of Gd-Tex(+2) on tumor metabolism and on tumor
      growth using a mouse mammary carcinoma model and (31)P nuclear magnetic resonance
      (NMR) experiments. Response to therapy was evaluated based on time for the tumor
      to regrow to pretreatment size and also tumor doubling time. RESULTS: (31)P NMR
      experiments indicated that Gd-Tex(+2) effected tumor energy metabolism during the
      first 24 hours postadministration. A decrease in phosphocreatine was noted at 2
      (p < 0.04), 6 (p < 0.006), and 24 (p < 0.001) hours post Gd-Tex(+2). A decrease
      in nucleoside triphosphates was noted only at 2 hours (p < 0.02), with subsequent
      recovery at 6 hours. Phosphocreatine in control (saline treated) tumors showed a
      significant decrease only at 24 hours (p < 0.01). Irradiation at 2 and 6 hours
      post Gd-Tex(+2) induced an enhanced effect compared to radiation alone as
      measured by analyzing the growth curves, maximum tumor volumes, and the time for
      the tumors to regrow to their initial volumes. Irradiation at 24 hours post Gd
      Tex(+2) induced a modest enhancement in tumor growth delay compared to radiation
      alone. DISCUSSION: NMR spectroscopy may be useful for monitoring tumor metabolism
      after treatment with Gd-Tex(+2) and administering radiation during the time of
      maximal efficacy of Gd-Tex(+2).

PMID- 11286847
TI  - Acidic environment modifies heat- or radiation-induced apoptosis in human
      maxillary cancer cells.
AB  - PURPOSE: The effects of hyperthermia or irradiation on cell killing and induction
      of apoptosis were evaluated using human maxillary carcinoma IMC-3 cells and low
      pH (pH 6.8) adapted cells (IMC-3-pH). METHODS AND MATERIALS: Cellular heat
      sensitivity or radiosensitivity was determined using the clonogenic assay.
      Apoptosis was assessed on the basis of a flow cytometric determination of the DNA
      content, DNA fragmentation, and poly(ADP-ribose)polymerase cleavage. RESULTS:
      When IMC-3 cells or IMC-3-pH cells were exposed to heat at 44 degrees C in pH 6.8
      medium, an increase in thermosensitivity was observed compared with when the IMC
      3 cells were exposed to heat at 44 degrees C in pH 7.4 medium. However, the
      selective reduction in survival was not observed after irradiation. In IMC-3
      cells, apoptosis after heating at 44 degrees C for 60 min in pH 7.4 medium
      occurred earlier than that after 8 Gy irradiation, although both thermal and
      irradiated doses decreased the cell count to 10%. The degree of apoptosis after
      heating at pH 6.8 in IMC-3 cells or IMC-3-pH cells was greater than that at pH
      7.4 in IMC-3 cells. However, the degree of apoptosis after 8 Gy irradiation at pH
      6.8 in IMC-3 cells or IMC-3-pH cells was smaller than that at pH 7.4 in IMC-3
      cells. CONCLUSION: Hyperthermia treatment is more effective at inducing apoptosis
      than radiation is in tumors that contain a population of low pH adapted cells.

PMID- 11286848
TI  - The potential impact of treatment variations on the results of radiotherapy of
      the internal mammary lymph node chain: a quality-assurance report on the dummy
      run of EORTC Phase III randomized trial 22922/10925 in Stage I--III breast
      cancer(1).
AB  - PURPOSE: To present the results of the dummy run of the European Organization for
      Research and Treatment of Cancer (EORTC) trial investigating the role of adjuvant
      internal mammary and medial supraclavicular (IM-MS) irradiation in Stage I--III
      breast cancer. METHODS AND MATERIALS: All participating institutions were asked
      to produce a treatment plan without (Arm 1) and with (Arm 2) simultaneous IM-MS
      irradiation of 1 patient after mastectomy and of 1 patient after lumpectomy.
      Thirty-two dummy runs have been evaluated for compliance to protocol guidelines,
      with respect to treatment technique and dose prescription. RESULTS: A number of
      more or less important deviations in treatment setup and prescription have been
      found. The dose in the IM-MS region deviated significantly from the prescribed
      dose in 10% of the cases for Arm 1, and in 21% for Arm 2. Assuming a true 5% 10
      year survival benefit from optimal IM-MS irradiation, an increase of only 3.8%
      will be found due to this suboptimal dose distribution. CONCLUSION: In the dummy
      run, a number of potential systematic protocol deviations that might lead to
      false-negative results were detected. By providing recommendations to the
      participating institutions, we expect to improve the interinstitutional
      consistency and to promote a high quality irradiation in all institutions
      participating in the trial.

PMID- 11286849
TI  - Accurate in vivo dosimetry of a randomized trial of prostate cancer irradiation.
AB  - PURPOSE: To guarantee an accurate dose delivery, within +/- 2.5%, in a Phase III
      randomized trial of prostate cancer irradiation (68 vs. 78 Gy) by means of a
      comprehensive in vivo dosimetry program. METHODS AND MATERIALS: Prostate patients
      are generally treated in our clinic with a 3-field isocentric technique: an 8-MV
      anteroposterior beam and 2 18-MV wedged laterals. All fields are shaped
      conformally to the PTV. Patients were randomized between two dose levels of 68 Gy
      and 78 Gy. During treatment, the entrance and exit dose were measured for each
      patient with diodes. Special 2.5-mm thick steel build-up caps were applied to
      make the diodes appropriate for measurements in 18-MV photon beams as well.
      Portal images were used to verify the correct position of the diodes and to
      detect and correct for gas filling in the rectum that may influence the exit dose
      reading. Entrance and exit dose measurements were converted to midplane dose,
      which was used in combination with a depth dose correction to obtain the dose at
      the specification point. An action level of 2.5% was applied. RESULTS: The added
      build-up for the diodes in the 18-MV beams resulted in correction factors that
      were only slightly sensitive to changes in beam setup and comparable to the
      corrections used in the 8-MV beams for diodes without extra build-up. The
      calibration factor increased almost linearly with cumulative dose: 0.7%/kGy for
      the 8-MV and 1.2%/kGy for the 18-MV photon beams. The introduction of average
      correction factors made the analysis easier, while keeping the accuracy within
      acceptable limits. In a period of 3 years, 225 patients were analyzed, from which
      8 patients needed to be corrected. The average ratio of measured and prescribed
      dose was 1.009 (standard deviation [SD] 0.012) for the total group treated on two
      linear accelerators. When the results were analyzed per accelerator, the ratios
      were 1.002 (SD, 0.001) for Accelerator A and 1.015 (SD, 0.001) for Accelerator B.
      This difference could be attributed to the cumulative effect of three small
      imperfections in the performance of Accelerator B that were well within the
      limits of our quality assurance program. CONCLUSION: Diodes can be used for
      accurate in vivo dosimetry during prostate irradiation in high-energy photon
      beams. The dose delivery in this randomized trial is guaranteed within the 2.5%
      limits on an individual patient basis. This could not be achieved without the in
      vivo dosimetry program, despite our high-standard quality assurance program of
      treatment delivery.

PMID- 11286850
TI  - Treatment planning using a dose-volume feasibility search algorithm.
AB  - PURPOSE: An approach to treatment plan optimization is presented that inputs dose
      -volume constraints and utilizes a feasibility search algorithm that seeks a set
      of beam weights so that the calculated dose distributions satisfy the dose-
      volume constraints. In contrast to a search for the "best" plan, this approach
      can quickly determine feasibility and point out the most restrictive of the
      predetermined constraints. METHODS AND MATERIALS: The cyclic subgradient
      projection (CSP) algorithm was modified to incorporate dose--volume constraints
      in a treatment plan optimization schema. The algorithm was applied to determine
      beam weights for several representative three-dimensional treatment plans.
      RESULTS: Using the modified CSP algorithm, we found that either a feasible
      solution to the dose--volume constraint problem was found or the program
      determined, after a predetermined set of iterations was performed, that no
      feasible solution existed for the particular set of dose--volume constraints. If
      no feasible solution existed, we relaxed several of the dose--volume constraints
      and were able to achieve a feasible solution. CONCLUSION: Feasibility search
      algorithms can be used in radiation treatment planning to generate a treatment
      plan that meets the dose--volume constraints established by the radiation
      oncologist. In the absence of a feasible solution, these algorithms can provide
      information to the radiation oncologist as to how the dose--volume constraints
      may be modified to achieve a feasible solution.

PMID- 11286851
TI  - Methodologies and tools for proton beam design for lung tumors.
AB  - PURPOSE: Proton beams can potentially increase the dose delivered to lung tumors
      without increasing the dose to critical normal tissues because protons can be
      stopped before encountering the normal tissues. This potential can only be
      realized if tissue motion and planning uncertainties are correctly included
      during planning. This study evaluated several planning strategies to determine
      which method best provides adequate tumor coverage, minimal normal tissue
      irradiation, and simplicity of use. METHODS AND MATERIALS: Proton beam treatment
      plans were generated using one or more of three different planning strategies.
      These strategies included designing apertures and boluses to the PTV, apertures
      to the PTV and boluses to the CTV, and aperture and bolus to the CTV. RESULTS:
      The planning target volume as specified in ICRU Report 50 can be used only to
      design the lateral margins of beams, because the distal and proximal margins
      resulting from CT number uncertainty, beam range uncertainty, tissue motions, and
      setup uncertainties, are different than the lateral margins resulting from these
      same factors. The best strategy for target coverage with the planning tools
      available overirradiated some normal tissues unnecessarily. The available tools
      also made the planning of lung tumors difficult. CONCLUSIONS: This study
      demonstrated that inclusion of target motion and setup uncertainties into a plan
      should be performed in the beam design step instead of creating new targets. New
      computerized treatment planning system tools suggested by this study will ease
      planning, facilitate abandonment of the PTV concept, improve conformance of the
      dose distribution to the target, and improve conformal avoidance of critical
      normal tissues.

PMID- 11286852
TI  - A comparison of dose distributions of proton and photon beams in stereotactic
      conformal radiotherapy of brain lesions.
AB  - PURPOSE: Micromultileaf collimators (mMLC) have recently been introduced to
      conform photon beams in stereotactic irradiation of brain lesions. Proton beams
      and stereotactic conformal radiotherapy (SCRT) can be used to tailor the dose to
      nonspherical targets, as most tumors of the brain are irregularly shaped.
      Comparative planning of brain lesions using either proton or stereotactically
      guided photon beams was done to assess the institution's clinically available
      modality for three-dimensional conformal radiotherapy. METHODS AND MATERIALS: For
      the photon treatment, multiple stereotactically guided uniform intensity beams
      from a linear accelerator were used, each conformed to a projection of the
      planning target volume (PTV) by a mMLC. Proton beams were delivered from an
      isocentrically mounted gantry, using the spot-scanning technique and energy
      modulation. Seven patients were scanned in a stereotactic frame; target volumes
      and organs at risk (OAR) were delineated with the help of MR images. Four
      different lesions were selected: (1) concave, (2) ellipsoid isolated, (3)
      superficial and close to an organ at risk, and (4) irregular complex. Dose
      distributions in the PTV and critical structures were calculated using three
      dimensional treatment-planning systems, followed by both a quantitative (by dose-
      volume histogram and conformity index) and qualitative (visual inspection)
      assessment of the plans. RESULTS: A high degree of conformation was achieved with
      a mMLC and stereotactic uniform intensity beams with comparable conformity
      indices to protons for 5 out of 7 plans, especially for superficial or spherical
      lesions. In the cases studied, the conformity index was better for protons than
      for photons for complex or concave lesions, or when the PTV was in the
      neighborhood of critical structures. CONCLUSION: The results for the cases
      studied, show that for simple geometries or for superficial lesions, there is no
      advantage in using protons. However, for complex PTV shapes, or when the PTV is
      in the vicinity of critical structures, protons seem to be potentially better
      than the fixed-field photon technique.

PMID- 11286853
TI  - Dynamic arc radiosurgery and radiotherapy: commissioning and verification of dose
      distributions.
AB  - PURPOSE: Conformal stereotactic radiosurgery and radiotherapy using a linear
      accelerator and a micromultileaf collimator (mMLC) offer the possibility of
      irradiating irregularly shaped target volumes. Dynamic arc radiosurgery and
      radiotherapy, i.e., stereotactic radiation therapy combining a moving gantry with
      a dynamic mMLC, enable the radiation even of lesions with concave structures.
      METHODS AND MATERIALS: The dynamic arc method requires additional tools for
      quality assurance (QA) and three-dimensional verification at a high spatial
      resolution. A QA program was developed. Dose distributions of planning target
      volumes with concavities were investigated in polymer gel phantoms. The radiation
      induced change of the relaxation rate R(2) was measured by magnetic resonance
      imaging. The distributions were compared with image processing tools. RESULTS:
      Using the therapy-planning software BrainSCAN 4.0 (and 4.1 beta) in combination
      with the mMLC m3, deviations between the planned and measured 90% isodoses of
      about 2 mm were registered in the isocenter plane. Three-dimensional verification
      was feasible in the range of accuracy achieved in planning and dose measurement.
      CONCLUSIONS: Dynamic arc radiosurgery and radiotherapy offer excellent
      conformation even for complicated planning target volumes with concavities. The
      dose distribution calculated with the treatment-planning software used can be
      accomplished with the available equipment. Patients can be treated by dynamic arc
      radiosurgery and radiotherapy.

PMID- 11286854
TI  - Effect of Foley catheters on seed positions and urethral dose in (125)I and
      (103)Pd prostate implants.
AB  - PURPOSE: To estimate the perturbation of seed position and urethral dose,
      subsequent to withdrawal of urethral catheters. METHODS AND MATERIALS: A
      mathematical model based on the volume incompressibility of tissues was used to
      compute seed positions and doses following removal of the Foley. The model
      assumed that the central axis of the urethra remains stationary, and that
      prostate tissue and seeds move radially toward the center of the urethra to fill
      the void left by the catheter. Seed motion has also been measured using
      transrectal ultrasound. RESULTS: Based on the computations, seeds located
      originally close to the urethra travel relatively large distances toward the
      urethra upon Foley removal, whereas seeds located further away move substantially
      less. This seed motion leads to higher urethral doses than shown in a standard
      treatment plan. Dose enhancements increase with catheter size, decrease with
      increasing prostate volume, are more pronounced for (103)Pd than for (125)I, and
      range between 3.5% and 32.4%. Postimplant dosimetry is equally affected if images
      are taken with urethral catheters in place, showing lower urethral doses than
      actually delivered. Preliminary ultrasound based measurements of seed motion
      agree with the theory. CONCLUSION: During the implantation procedure, 12 fr or
      smaller urethral catheters are preferable to larger diameter catheters if urine
      drainage is sufficient. Treatment planners should avoid planning seeds at 5 mm or
      closer from the urethra. Special caution is indicated in prostates having about
      20 cm(3) or smaller volumes, and when (103)Pd is used. Postimplant dosimetry is
      susceptible to the same errors.

PMID- 11286855
TI  - A simplified shielding approach for limiting fetal dose during radiation therapy
      of pregnant patients.
AB  - PURPOSE: To investigate the effectiveness of a simple and practical shielding
      device to reduce fetal dose for a patient undergoing radiation therapy of
      nasopharyngeal carcinoma. METHODS AND MATERIALS: Using 5-cm-thick lead bricks and
      a heavy-duty steel cart, a 50 x 50-cm portable shield was designed and fabricated
      to reduce fetal dose due to collimator scatter and head leakage radiation. With
      the gantry at 90 degrees /270 degrees the shield can be easily positioned between
      the machine head and the fetus to reduce peripheral dose. Dose measurements for 6
      MV X-rays and 9-MeV electrons have been made, utilizing a Rando phantom, to
      quantify the effect of the shield. RESULTS: Measurements show that the peripheral
      dose to the fetus can be reduced by 60% when the simple shielding device is used.

PMID- 11286856
TI  - Does the standardized helmet technique lead to adequate coverage of the
      cribriform plate? An analysis of current practice with respect to the ICRU 50
      report.
AB  - PURPOSE: To investigate whether the standardized helmet technique adequately
      covers the cribriform plate. METHODS AND MATERIALS: For 11 patients with acute
      leukemia or primary intracerebral neoplasms undergoing irradiation with the
      standardized helmet technique, three-dimensional isodose distributions were
      evaluated with special respect to the dose to the cribriform plate and the ocular
      lenses. RESULTS: The average dose received by 95% of the cribriform plate with
      the standardized helmet technique was 85% of the prescribed dose. To enclose the
      cribriform plate by the 95% isodose (according to the ICRU 50 report) with a 10
      mm safety margin allowing for deviations during treatment planning and delivery,
      the eye block had to be moved in the ventrocaudal direction with an average
      vector length of 13.6 mm. Consequently, the mean dose received by 5% of the
      lenses rose from 18% to 91% of the prescribed total dose. CONCLUSION: Sufficient
      lens shielding is usually not compatible with safe irradiation of the frontobasis
      by the standardized helmet technique.

PMID- 11286857
TI  - Dynamic arc radiosurgery field shaping: a comparison with static field conformal
      and noncoplanar circular arcs.
AB  - PURPOSE: Recent advances in field-shaping technology and linac multileaf
      collimator (MLC) integration have resulted in new approaches to performing
      stereotactic radiosurgery. We present a modeling study comparing the absolute
      dose distributions from three radiosurgery delivery techniques: a conventional
      approach utilizing noncoplanar circular arcs, a static field conformal approach,
      and a dynamic arc field-shaping approach. In the latter, the MLC leaves more in a
      continuous fashion, conforming to the beam's-eye-view projection of the target at
      every increment along the path of an arc. METHODS AND MATERIALS: For the
      analysis, we devised a simulated target consisting of three overlapping spheres.
      This was chosen because it offered a straightforward planning approach for all
      three techniques, primarily the multiple isocenter approach. In addition, three
      representative cases were selected from the prior radiosurgery experience. These
      range in increasing size, from 0.50 to 9.79 cm(3), and in complexity, requiring
      from 3 isocenters to 16 in the case of circular arcs. In each situation, the
      goals were twofold: (1) to cover the entire volume with as high an appropriate
      isodose level (90% in the case of the conformal and dynamic arc techniques, 50%
      in the case of circular collimators) while (2) minimizing the dose to normal
      brain and where applicable, any adjacent radiation-sensitive structures. Because
      of the latter requirement, a single isocenter circular arc approach was ruled out
      for the analysis. RESULTS: In the case of large or irregularly shaped lesions,
      the circular arc technique requires multiple isocenters, producing a high level
      of dose heterogeneity within the target volume. Both the static field and dynamic
      arc conformal techniques, as with all single isocenter approaches, produce a
      highly homogeneous dose throughout the target region. For a given large dose,
      peripheral dose is decreased as additional beams or arc degrees are added with
      either of the conformal approaches. Dose--volume histogram analysis evaluating
      the peripheral dose shows that, in many cases, dose to surrounding structures can
      be reduced through the use of a conformal static or dynamic arc approach over the
      conventional multiple isocenter, circular arc techniques. CONCLUSIONS: Dynamic
      arc shaping is an efficient and effective method for accurately delivering a
      homogeneous target dose while simultaneously minimizing peripheral dose in
      radiosurgery applications.

PMID- 11286858
TI  - Three-dimensional accuracy and interfractional reproducibility of patient
      fixation and positioning using a stereotactic head mask system.
AB  - PURPOSE: Conformal radiotherapy in the head and neck region requires precise and
      reproducible patient setup. The definition of safety margins around the clinical
      target volume has to take into account uncertainties of fixation and positioning.
      Data are presented to quantify the involved uncertainties for the system used.
      METHODS AND MATERIALS: Interfractional reproducibility of fixation and
      positioning of a target point in the brain was evaluated by biplanar films. 118
      film pairs obtained at 52 fractions in 4 patients were analyzed. The setup was
      verified at the actual treatment table position by diagnostic X-ray units aligned
      to the isocenter and by a stereotactic X-ray localization technique. The
      stereotactic coordinates of the treated isocenter, of fiducials on the mask, and
      of implanted internal markers within the patient were measured to determine
      systematic and random errors. The data are corrected for uncertainty of the
      localization method. RESULTS: Displacements in target point positioning were 0.35
      +/- 0.41 mm, 1.22 +/- 0.25 mm, and -0.74 +/- 0.32 mm in the x, y, and z
      direction, respectively. The reproducibility of the fixation of the patient's
      head within the mask was 0.48 mm (x), 0.67 mm (y), and 0.72 mm (z). Rotational
      uncertainties around an axis parallel to the x, y, and z axis were 0.72 degrees,
      0.43 degrees, and 0.70 degrees, respectively. A simulation, based on the acquired
      data, yields a typical radial overall uncertainty for positioning and fixation of
      1.80 +/- 0.60 mm. CONCLUSIONS: The applied setup technique showed to be highly
      reproducible. The data suggest that for the applied technique, a safety margin
      between clinical and planning target volume of 1-2 mm along one axis is
      sufficient for a target at the base of skull.

PMID- 11286859
TI  - Young Investigators Workshop--Radiation Research Program, Radiation Oncology
      Sciences Program, National Cancer Institute, NIH, August 1-2 2000.

PMID- 11286862
TI  - Lessons and questions from the structure of the Spo0A activation domain.
AB  - The carboxy-terminal domain of Spo0A in Bacillus subtilis is one of the few
      response regulator activation domains for which the structure is known. Here, we
      discuss some of the mutational data and biological roles of Spo0A in light of its
      structure.

PMID- 11286864
TI  - Chlamydia pneumoniae and multiple sclerosis: no significant association.
AB  - The cause of multiple sclerosis (MS) is unknown. Despite indications from
      epidemiological and identical-twin studies that MS is infectious, no virus or
      other infectious agent has been tightly linked to disease. The isolation of
      Chlamydia pneumoniae from the cerebrospinal fluid (CSF) of MS patients and the
      detection of both Chlamydia-specific DNA and antibody in MS CSF have been
      reported. Other analyses of brain and CSF have shown no significant difference in
      C. pneumoniae-specific DNA or antibody between MS and control subjects. Recent
      work has revealed intrathecal production of C. pneumoniae-specific IgG in only
      24% of MS patients compared with 5% of control patients. More importantly, the
      major CSF oligoclonal bands from MS patients did not react to C. pneumoniae.

PMID- 11286866
TI  - M. leprae genome sequence.

PMID- 11286865
TI  - It's easy to build your own microarrayer!
AB  - DNA microarrays are becoming the tool of choice for microbial gene-expression
      profiling and genotypic analysis. The construction of a gridding robot for the
      'in-house' production of microarrays is a choice worth considering, and offers
      distinct advantages over other options in terms of cost effectiveness and scale.
      Having built our own robot, we want to dispel some of the myths that might be
      associated with such a project, as well as provide practical advice for potential
      builders in the UK and Europe.

PMID- 11286867
TI  - Parasite variation provides hope for malaria vaccine design.

PMID- 11286868
TI  - Metabolomics breaks the silence.

PMID- 11286869
TI  - DC targeting by a bacterial OmpA.

PMID- 11286870
TI  - Genome sequence of E. coli O157:H7.

PMID- 11286871
TI  - Microbial genomics.

PMID- 11286880
TI  - Processing and export of peptide pheromones and bacteriocins in Gram-negative
      bacteria.
AB  - Cell-density-dependent gene expression is widespread in bacteria and is mediated
      by extracellular communication molecules. Gram-negative bacteria often use N-acyl
      homoserine lactones, whereas cell-cell signaling in Gram-positive bacteria is
      accomplished using post-translationally processed peptide pheromones. In many
      Gram-positive bacteria, export of these peptides requires the activity of a
      dedicated ATP-binding cassette (ABC) transporter, which cleaves off a typical
      leader peptide termed the double-glycine leader sequence concomitant with
      translocation across the membrane. Inspection of bacterial genome sequences has
      revealed the presence of similar ABC transporters, as well as genes encoding
      peptides with double-glycine-type leader sequences in Gram-negative bacteria, and
      it is suggested that the postulated transported peptides could perform a
      signaling function.

PMID- 11286881
TI  - Ureaplasma urealyticum: an opportunity for combinatorial genomics.
AB  - Examination of genomic or enzymatic activity data alone neither provides a
      complete picture of metabolic function or potential nor confidently reveals sites
      amenable to inhibition. Furthermore, in some cases, gene annotation and in aqua
      assays disagree by describing gene annotation without enzyme activity and enzyme
      activity without homologous annotation. The newly sequenced genome of Ureaplasma
      urealyticum (parvum) is another prokaryote example of the class Mollicutes where
      such confounding differences are observed. The little-considered role of some
      proteins as multifunctional enzymes - substitutes for 'missing' genes - could
      both partially explain the apparent anomalies and relate to any inaccurate
      deductions of inhibitor function. A combinatorial analysis involving available
      evidence of genomic sequence, transcription, translational phenomena, structure
      and enzymatic activity gives the best picture of the organism's vital metabolic
      alternatives.

PMID- 11286882
TI  - The ALS gene family of Candida albicans.
AB  - The ALS gene family of Candida albicans encodes large cell-surface glycoproteins
      that are implicated in the process of adhesion to host surfaces. ALS genes are
      also found in other Candida species that are isolated from cases of clinical
      disease. Genes in the ALS family are differentially regulated by physiologically
      relevant mechanisms. ALS genes exhibit several levels of variability including
      strain- and allele-specific size differences for the same gene, strain-specific
      differences in gene regulation, the absence of particular ALS genes in certain
      isolates, and additional ALS coding regions in others. The differential
      regulation and genetic variability of the ALS genes results in a diverse cell
      surface Als protein profile that is also affected by growth conditions. The ALS
      genes are one example of a gene family associated with pathogenicity mechanisms
      in C. albicans and other Candida species.

PMID- 11286883
TI  - Exploring the evolution of diversity in pathogen populations.
AB  - Pathogen biodiversity is an under-exploited source of inference regarding disease
      processes and the evolution of pathogens and pathogenesis. In addition, the
      structure of pathogen populations, especially for diverse organisms such as the
      meningococcus, has implications for public health interventions including
      vaccination and antibiotic use. The predominant paradigm for interpreting
      bacterial diversity has been the clonal population structure, which has been
      modified by the incorporation of the effects of horizontal genetic exchange.
      Multilocus models of variable antigens, which explore the effects of immune
      selection, provide alternative explanations for structured diversity in pathogen
      populations.

PMID- 11286884
TI  - The tc genes of Photorhabdus: a growing family.
AB  - The toxin complex (tc) genes of Photorhabdus encode insecticidal, high molecular
      weight Tc toxins. These toxins have been suggested as useful alternatives to
      those derived from Bacillus thuringiensis for expression in insect-resistant
      transgenic plants. Although Photorhabdus luminescens is symbiotic with nematodes
      that kill insects, tc genes have recently been described from other insect
      associated bacteria such as Serratia entomophila, an insect pathogen, and
      Yersinia pestis, the causative agent of bubonic plague, which has a flea vector.
      Here, recent advances in our understanding of the tc gene family are reviewed in
      view of their potential development as insect-control agents.

PMID- 11286885
TI  - Dynamics of the transition between open and closed conformations in a calmodulin
      C-terminal domain mutant.
AB  - BACKGROUND: Calmodulin is a ubiquitous Ca(2+)-activated regulator of cellular
      processes in eukaryotes. The structures of the Ca(2+)-free (apo) and Ca(2+)
      loaded states of calmodulin have revealed that Ca(2+) binding is associated with
      a transition in each of the two domains from a closed to an open conformation
      that is central to target recognition. However, little is known about the
      dynamics of this conformational switch. RESULTS: The dynamics of the transition
      between closed and open conformations in the Ca(2+)-loaded state of the E140Q
      mutant of the calmodulin C-terminal domain were characterized under equilibrium
      conditions. The exchange time constants (tau(ex)) measured for 42 residues range
      from 13 to 46 micros, with a mean of 21 +/- 3 micros. The results suggest that
      tau(ex) varies significantly between different groups of residues and that
      residues with similar values exhibit spatial proximity in the structures of apo
      and/or Ca(2+)-saturated wild-type calmodulin. Using data for one of these groups,
      we obtained an open population of p(o) = 0.50 +/- 0.17 and a closed --> open rate
      constant of k(o) = x 10(4) s(-1). CONCLUSIONS: The conformational exchange
      dynamics appear to involve locally collective processes that depend on the
      structural topology. Comparisons with previous results indicate that similar
      processes occur in the wild-type protein. The measured rates match the estimated
      Ca(2+) off rate, suggesting that Ca(2+) release may be gated by the
      conformational dynamics. Structural interpretation of estimated chemical shifts
      suggests a mechanism for ion release.

PMID- 11286886
TI  - Crystal structure of the archaeal holliday junction resolvase Hjc and
      implications for DNA recognition.
AB  - BACKGROUND: Homologous recombination is a crucial mechanism in determining
      genetic diversity and repairing damaged chromosomes. Holliday junction is the
      universal DNA intermediate whose interaction with proteins is one of the major
      events in the recombinational process. Hjc is an archaeal endonuclease, which
      specifically resolves the junction DNA to produce two separate recombinant DNA
      duplexes. The atomic structure of Hjc should clarify the mechanisms of the
      specific recognition with Holliday junction and the catalytic reaction. RESULTS:
      The crystal structure of Hjc from the hyperthermophilic archaeon Pyrococcus
      furiosus has been determined at 2.0 A resolution. The active Hjc molecule forms a
      homodimer, where an extensive hydrophobic interface tightly assembles two
      subunits of a single compact domain. The folding of the Hjc subunit is clearly
      different from any other Holliday junction resolvases thus far known. Instead, it
      resembles those of type II restriction endonucleases, including the
      configurations of the active site residues, which constitute the canonical
      catalytic motifs. The dimeric Hjc molecule displays an extensive basic surface on
      one side, which contains many conserved amino acids, including those in the
      active site. CONCLUSIONS: The architectural similarity of Hjc to restriction
      endonucleases allowed us to construct a putative model of the complex with
      Holliday junction. This model accounts for how Hjc recognizes and resolves the
      junction DNA in a specific manner. Mutational and biochemical analyses highlight
      the importance of some loops and the amino terminal region in interaction with
      DNA.

PMID- 11286887
TI  - Structural basis for the ADP-specificity of a novel glucokinase from a
      hyperthermophilic archaeon.
AB  - BACKGROUND: ATP is the most common phosphoryl group donor for kinases. However,
      certain hyperthermophilic archaea such as Thermococcus litoralis and Pyrococcus
      furiosus utilize unusual ADP-dependent glucokinases and phosphofructokinases in
      their glycolytic pathways. These ADP-dependent kinases are homologous to each
      other but show no sequence similarity to any of the hitherto known ATP-dependent
      enzymes. RESULTS: We solved the crystal structure at 2.3 A resolution of an ADP
      dependent glucokinase from T. litoralis (tlGK) complexed with ADP. The overall
      structure can be divided into large and small alpha/beta domains, and the ADP
      molecule is buried in a shallow pocket in the large domain. Unexpectedly, the
      structure was similar to those of two ATP-dependent kinases, ribokinase and
      adenosine kinase. Comparison based on three-dimensional structure revealed that
      several motifs important both in structure and function are conserved, and the
      recognition of the alpha- and beta-phosphate of the ADP in the tlGK was almost
      identical with the recognition of the beta- and gamma-phosphate of ATP in these
      ATP-dependent kinases. CONCLUSIONS: Noticeable points of our study are the first
      structure of ADP-dependent kinase, the structural similarity to members of the
      ATP-dependent ribokinase family, its rare nucleotide specificity caused by a
      shift in nucleotide binding position by one phosphate unit, and identification of
      the residues that discriminate ADP- and ATP-dependence. The strict conservation
      of the binding site for the terminal and adjacent phosphate moieties suggests a
      common ancestral origin of both the ATP- and ADP-dependent kinases.

PMID- 11286888
TI  - Three-dimensional structure of a voltage-gated potassium channel at 2.5 nm
      resolution.
AB  - BACKGROUND: The voltage-gated potassium channel Shaker from Drosophila consists
      of a tetramer of identical subunits, each containing six transmembrane segments.
      The atomic structure of a bacterial homolog, the potassium channel KcsA, is much
      smaller than Shaker. It does not have a voltage sensor and other important
      domains like the N-terminal tetramerization (T1) domain. The structure of these
      additional elements has to be studied in the more complex voltage-gated channels.
      RESULTS: We determined the three-dimensional structure of the entire Shaker
      channel at 2.5 nm resolution using electron microscopy. The four-fold symmetric
      structure shows a large and a small domain linked by thin 2 nm long connectors.
      To interpret the structure, we used the crystal structures of the isolated T1
      domain and the KcsA channel. A unique density assignment was made based on the
      symmetry and dimensions of the crystal structures and domains, identifying the
      smaller domain as the cytoplasmic mass of Shaker containing T1 and the larger
      domain as embedded in the membrane. CONCLUSIONS: The two-domain architecture of
      the Shaker channel is consistent with the recently proposed "hanging gondola"
      model for the T1 domain, putting the T1 domain at a distance from the membrane
      domain but attached to it by thin connectors. The space between the two domains
      is sufficient to permit cytoplasmic access of ions and the N-terminal
      inactivation domain to the pore region. A hanging gondola architecture has also
      been observed in the nicotinic acetylcholine receptor and the KcsA structure,
      suggesting that it is a common element of ion channels.

PMID- 11286889
TI  - Structural basis of the enhanced stability of a mutant ribozyme domain and a
      detailed view of RNA--solvent interactions.
AB  - BACKGROUND: The structure of P4-P6, a 160 nucleotide domain of the self-splicing
      Tetrahymena thermophila intron, was solved previously. Mutants of the P4-P6 RNA
      that form a more stable tertiary structure in solution were recently isolated by
      successive rounds of in vitro selection and amplification. RESULTS: We show that
      a single-site mutant (Delta C209) possessing greater tertiary stability than wild
      type P4-P6 also crystallizes much more rapidly and under a wider variety of
      conditions. The crystal structure provides a satisfying explanation for the
      increased stability of the mutant; the deletion of C209 allows the adjacent
      bulged adenine to enter the P4 helix and form an A-G base pair, presumably
      attenuating the conformational flexibility of the helix. The structure of another
      mutant (Delta A210) was also solved and supports this interpretation. The
      crystals of Delta C209 diffract to a higher resolution limit than those of wild
      type RNA (2.25 A versus 2.8 A), allowing assignment of innersphere and
      outersphere coordination contacts for 27 magnesium ions. Structural analysis
      reveals an intricate solvent scaffold with a preponderance of ordered water
      molecules on the inside rather than the surface of the folded RNA domain.
      CONCLUSIONS: In vitro evolution facilitated the identification of a highly
      stable, structurally homogeneous mutant RNA that was readily crystallizable.
      Analysis of the structure suggests that improving RNA secondary structure can
      stabilize tertiary structure and perhaps promote crystallization. In addition,
      the higher resolution model provides new details of metal ion-RNA interactions
      and identifies a core of ordered water molecules that may be integral to RNA
      tertiary structure formation.

PMID- 11286890
TI  - Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty
      acids elucidate its catalytic machinery.
AB  - BACKGROUND: beta-ketoacyl-acyl carrier protein synthase (KAS) I is vital for the
      construction of the unsaturated fatty acid carbon skeletons characterizing E.
      coli membrane lipids. The new carbon-carbon bonds are created by KAS I in a
      Claisen condensation performed in a three-step enzymatic reaction. KAS I belongs
      to the thiolase fold enzymes, of which structures are known for five other
      enzymes. RESULTS: Structures of the catalytic Cys-Ser KAS I mutant with
      covalently bound C10 and C12 acyl substrates have been determined to 2.40 and
      1.85 A resolution, respectively. The KAS I dimer is not changed by the formation
      of the complexes but reveals an asymmetric binding of the two substrates bound to
      the dimer. A detailed model is proposed for the catalysis of KAS I. Of the two
      histidines required for decarboxylation, one donates a hydrogen bond to the
      malonyl thioester oxo group, and the other abstracts a proton from the leaving
      group. CONCLUSIONS: The same mechanism is proposed for KAS II, which also has a
      Cys-His-His active site triad. Comparison to the active site architectures of
      other thiolase fold enzymes carrying out a decarboxylation step suggests that
      chalcone synthase and KAS III with Cys-His-Asn triads use another mechanism in
      which both the histidine and the asparagine interact with the thioester oxo
      group. The acyl binding pockets of KAS I and KAS II are so similar that they
      alone cannot provide the basis for their differences in substrate specificity.

PMID- 11286891
TI  - Structural basis for the function of pyridoxine 5'-phosphate synthase.
AB  - BACKGROUND: Pyridoxal 5'-phosphate is the active form of vitamin B(6) that acts
      as an essential, ubiquitous coenzyme in amino acid metabolism. In Escherichia
      coli, the pathway of the de novo biosynthesis of vitamin B(6) results in the
      formation of pyridoxine 5'-phosphate (PNP), which can be regarded as the first
      synthesized B(6) vitamer. PNP synthase (commonly referred to as PdxJ) is a
      homooctameric enzyme that catalyzes the final step in this pathway, a complex
      intramolecular condensation reaction between 1-deoxy-D-xylulose-5'-phosphate and
      1-amino-acetone-3-phosphate. RESULTS: The crystal structure of E. coli PNP
      synthase was solved by single isomorphous replacement with anomalous scattering
      and refined at a resolution of 2.0 A. The monomer of PNP synthase consists of one
      compact domain that adopts the abundant TIM barrel fold. Intersubunit contacts
      are mediated by three additional helices, respective to the classical TIM barrel
      helices, generating a tetramer of symmetric dimers with 422 symmetry. In the
      shared active sites of the active dimers, Arg20 is directly involved in substrate
      binding of the partner monomer. Furthermore, the structure of PNP synthase with
      its physiological products, PNP and P(i), was determined at 2.3 A resolution,
      which provides insight into the dynamic action of the enzyme and allows us to
      identify amino acids critical for enzymatic function. CONCLUSION: The high
      resolution structures of the free enzyme and the enzyme-product complex of E.
      coli PNP synthase suggest essentials of the enzymatic mechanism. The main
      catalytic features are active site closure upon substrate binding by
      rearrangement of one C-terminal loop of the TIM barrel, charge-charge
      stabilization of the protonated Schiff-base intermediate, the presence of two
      phosphate binding sites, and a water channel that penetrates the beta barrel and
      allows the release of water molecules in the closed state. All related PNP
      synthases are predicted to fold into a similar TIM barrel pattern and have
      comparable active site architecture. Thus, a common mechanism can be anticipated.

PMID- 11286892
TI  - The structure of the fusion glycoprotein of Newcastle disease virus suggests a
      novel paradigm for the molecular mechanism of membrane fusion.
AB  - BACKGROUND: Membrane fusion within the Paramyxoviridae family of viruses is
      mediated by a surface glycoprotein termed the "F", or fusion, protein. Membrane
      fusion is assumed to involve a series of structural transitions of F from a
      metastable (prefusion) state to a highly stable (postfusion) state. No detail is
      available at the atomic level regarding the metastable form of these proteins or
      regarding the transitions accompanying fusion. RESULTS: The three-dimensional
      structure of the fusion protein of Newcastle disease virus (NDV-F) has been
      determined. The trimeric NDV-F molecule is organized into head, neck, and stalk
      regions. The head is comprised of a highly twisted beta domain and an additional
      immunoglobulin-like beta domain. The neck is formed by the C-terminal extension
      of the heptad repeat region HR-A, capped by a four-helical bundle. The C terminus
      of HR-A is encased by a further helix HR-C and a 4-stranded beta sheet. The stalk
      is formed by the remaining visible portion of HR-A and by polypeptide immediately
      N-terminal to the C-terminal heptad repeat region HR-B. An axial channel extends
      through the head and neck and is fenestrated by three large radial channels
      located approximately at the head-neck interface. CONCLUSION: We propose that
      prior to fusion activation, the hydrophobic fusion peptides in NDV-F are
      sequestered within the radial channels within the head, with the central HR-A
      coiled coil being only partly formed. Fusion activation then involves, inter
      alia, the assembly of a complete HR-A coiled coil, with the fusion peptides and
      transmembrane anchors being brought into close proximity. The structure of NDV-F
      is fundamentally different than that of influenza virus hemagglutinin, in that
      the central coiled coil is in the opposite orientation with respect to the viral
      membrane.

PMID- 11286893
TI  - PhosphoSerine/threonine binding domains: you can't pSERious?
AB  - The fundamental biological importance of protein phosphorylation is underlined by
      the existence of more than 500 protein kinase genes within the human genome. In
      many cases, phosphorylation on serine, threonine, and tyrosine residues creates
      binding surfaces for a variety of phospho-amino acid binding proteins/modules.
      Here, we review the insights into serine/threonine phosphorylation-dependent
      signal transduction processes provided by structures of several of these proteins
      and their complexes.

PMID- 11286894
TI  - Seeing with S cones.
AB  - The S cone is highly conserved across mammalian species, sampling the retinal
      image with less spatial frequency than other cone photoreceptors. In human and
      monkey retina, the S cone represents typically 5-10% of the cone mosaic and
      distributes in a quasi-regular fashion over most of the retina. In the fovea, the
      S cone mosaic recedes from a central "S-free" zone whose size depends on the
      optics of the eye for a particular primate species: the smaller the eye, the less
      extreme the blurring of short wavelengths, and the smaller the zone. In the human
      retina, the density of the S mosaic predicts well the spatial acuity for S
      isolating targets across the retina. This acuity is likely supported by a
      bistratified retinal ganglion cell whose spatial density is about that of the S
      cone. The dendrites of this cell collect a depolarizing signal from S cones that
      opposes a summed signal from M and L cones. The source of this depolarizing
      signal is a specialized circuit that begins with expression of the L-AP4 or
      mGluR6 glutamate receptor at the S cone-->bipolar cell synapse. The pre-synaptic
      circuitry of this bistratified ganglion cell is consistent with its S-ON/(M+L)
      OFF physiological receptive field and with a role for the ganglion cell in
      blue/yellow color discrimination. The S cone also provides synapses to other
      types of retinal circuit that may underlie a contribution to the cortical areas
      involved with motion discrimination.

PMID- 11286895
TI  - Retinal research using the perfused mammalian eye.
AB  - The effort to isolate and maintain alive in vitro an intact mammalian eye is
      rewarded by the full control provided over the arterial input and exclusion of
      systemic regulatory or compensatory mechanisms. Electrical recording of typical
      light-evoked field potentials from retina and optic nerve can be complemented by
      single-cell recording. Thus, light-induced electrical activity reflects the
      function of the retinal pigment epithelium, of the layers of the retina and of
      the ganglion cells or their axons. Retinal function in vitro is documented by
      electrophysiological and morphological methods revealing subtle features of
      retinal information processing as well as optic nerve signals that approach-at
      threshold stimulus intensity-the human psychophysical threshold. Such sensitivity
      of third-order retinal neurons is described for the first time. This well
      controlled in vitro preparation has been used successfully for biophysical,
      metabolic and pharmacological studies. Examples are provided that demonstrate the
      marked sensibility of the rod system to changes in glucose supply. Moreover,
      histochemical identification of glycogen stores revealed labeling of the second-
      and third-order neurons subserving the rod system, in addition to labeling of
      Muller (glial) cells in the cat retina. The glycogen content of the cat retina is
      augmented by prolonged anesthesia, largely depleted by ischemia after enucleation
      and enhanced by insulin. Pharmacological experiments using agonists and
      antagonists of putative retinal neurotransmitters are summarized and outlined
      using the muscarinic cholinergic agonist QNB as an example. Actions and uptake of
      the neuromodulator adenosine are presented in detail, including inhibitory
      effects on physiologically characterized ganglion cells. Neuronal effects of
      adenosine are distinguished from those resulting from vasodilatation and from
      glycogenolysis induced by the neuromodulator. To open the blood-retina barrier, a
      hyperosmotic challenge can be applied transiently. This process is monitored
      histochemically using FITC-albumin and with electrophysiological parameters.
      Changes in vitreo-scleral resistance and in the amplitude of the EOG-light peak
      appear to reflect the open/closed status of the barrier. This overview of the
      uses of the isolated perfused mammalian eye in retinal research concludes with a
      discussion of potential implications for clinically relevant topics.

PMID- 11286896
TI  - Vasospasm, its role in the pathogenesis of diseases with particular reference to
      the eye.
AB  - Vasospasm can have many different causes and can occur in a variety of diseases,
      including infectious, autoimmune, and ophthalmic diseases, as well as in
      otherwise healthy subjects. We distinguish between the primary vasospastic
      syndrome and secondary vasospasm. The term "vasospastic syndrome" summarizes the
      symptoms of patients having such a diathesis as responding with spasm to stimuli
      like cold or emotional stress. Secondary vasospasm can occur in a number of
      autoimmune diseases, such as multiple sclerosis, lupus erythematosus,
      antiphospholipid syndrome, rheumatoid polyarthritis, giant cell arteritis,
      Behcet's disease, Buerger's disease and preeclampsia, and also in infectious
      diseases such as AIDS. Other potential causes for vasospasm are hemorrhages,
      homocysteinemia, head injury, acute intermittent porphyria, sickle cell disease,
      anorexia nervosa, Susac syndrome, mitochondriopathies, tumors, colitis ulcerosa,
      Crohn's disease, arteriosclerosis and drugs. Patients with primary vasospastic
      syndrome tend to suffer from cold hands, low blood pressure, and even migraine
      and silent myocardial ischemia. Valuable diagnostic tools for vasospastic
      diathesis are nailfold capillary microscopy and angiography, but probably the
      best indicator is an increased plasma level of endothelin-1. The eye is
      frequently involved in the vasospastic syndrome, and ocular manifestations of
      vasospasm include alteration of conjunctival vessels, corneal edema, retinal
      arterial and venous occlusions, choroidal ischemia, amaurosis fugax, AION, and
      glaucoma. Since the clinical impact of vascular dysregulation has only really
      been appreciated in the last few years, there has been little research in the
      according therapeutic field. The role of calcium channel blockers, magnesium,
      endothelin and glutamate antagonists, and gene therapy are discussed.

PMID- 11286897
TI  - Rod vision: pathways and processing in the mammalian retina.
AB  - Bipolar cells in the mammalian retina are postsynaptic to either rod or cone
      photoreceptors, thereby segregating their respective signals into parallel
      vertical streams. In contrast to the cone pathways, only one type of rod bipolar
      cell exists, apparently limiting the routes available for the propagation of rod
      signals. However, due to numerous interactions between the rod and cone
      circuitry, there is now strong evidence for the existence of up to three
      different pathways for the transmission of scotopic visual information. Here we
      survey work over the last decade or so that have defined the structure and
      function of the interneurons subserving the rod pathways in the mammalian retina.
      We have focused on: (1) the synaptic ultrastructure of the interneurons; (2)
      their light-evoked physiologies; (3) localization of specific transmitter
      receptor subtypes; (4) plasticity of gap junctions related to changes in
      adaptational state; and (5) the functional implications of the existence of
      multiple rod pathways. Special emphasis has been placed on defining the circuits
      underlying the different response components of the AII amacrine cell, a central
      element in the transmission of scotopic signals.

PMID- 11286898
TI  - Immunological and aetiological aspects of macular degeneration.
AB  - Aetiological and immunological aspects of AMD, a leading cause of blindness in
      Western countries, have been reviewed. Developmental studies suggest that
      anatomical features unique to the fovea result in a critical relationship between
      metabolic demand and blood supply at the macula, which is maintained throughout
      life. Recent studies show a sufficient degree of consistency in the link between
      smoking and both dry and wet AMD to regard it as causative. Dry AMD is considered
      to be the natural endstage of the disease; epidemiological and morphological
      studies point to choroidal vascular atrophy as the causative event and it is
      suggested that signals associated with acute vascular compromise lead to the
      development of subretinal neovascularisation. The relationship between sub
      pigment epithelial deposits, including basal laminar deposit, and the
      pathogenesis of AMD is examined. Much of the literature is consistent with a
      choroidal origin for the constituents of drusen. The blood-retinal barrier
      preserves the physiological environment of the neural retina and limits
      inflammatory responses. The factors, including cytokines, adhesion molecules and
      the presence of resident immunocompetent cells (microglia), which determine the
      immune status of the retina are considered. Historical descriptions of the
      involvement of inflammatory cells are provided, evidence implicating inflammation
      in the pathogenesis of AMD involving macrophages, giant cells and microglia has
      been derived from observations of human and animal subretinal neovascular
      lesions. The role of humoral factors such as anti-retinal autoantibodies and
      acute phase proteins together with clinical observations has been surveyed. Taken
      together these data demonstrate the involvement of both cellular and humoral
      immunity in the pathogenesis of AMD. It remains to be determined to what degree
      the influence of immunity is causative or contributory in both wet and dry AMD,
      however, the use of anti-inflammatory agents to ameliorate the condition further
      indicates the existence of an inflammatory component.

PMID- 11286900
TI  - Switching on plant genes by external chemical signals.
AB  - During the past decade there has been rapidly increasing interest in the role of
      plant volatiles in insect-plant interactions and the induction of plant defence
      systems by both pathogens and herbivores. Scientists are striving to link the
      proximate studies elucidating pathways and genes with the ultimate adaptive
      studies that attempt to explain their ecological role. However, we still do not
      know whether plants 'talk' to one another by employing 'phytopheromones'.

PMID- 11286902
TI  - Mining out for iron.

PMID- 11286899
TI  - AtMYB4: a transcription factor general in the battle against UV.
AB  - Mounting evidence indicates that members of the large family of plant MYB
      proteins are involved in the transcriptional regulation of an array of metabolic
      and developmental processes. Recently, the Arabidopsis thaliana MYB, AtMYB4, was
      shown to regulate the accumulation of the UV-protectant compound sinapoylmalate
      by repressing the transcription of the gene encoding the phenylpropanoid enzyme
      cinnamate 4-hydroxylase. AtMYB4 is thus a key regulator of phenylpropanoid
      pathway gene expression, and is the first example of a MYB protein that functions
      as a transcriptional repressor.

PMID- 11286903
TI  - A Nod and a wave: calcium signals during nodulation.

PMID- 11286904
TI  - Oxygen transport in the static plant cell system.

PMID- 11286905
TI  - Smart plants or stealthy bugs?

PMID- 11286918
TI  - Peroxisomes as a source of reactive oxygen species and nitric oxide signal
      molecules in plant cells.
AB  - The important role of plant peroxisomes in a variety of metabolic reactions such
      as photorespiration, fatty acid beta-oxidation, the glyoxylate cycle and
      generation-degradation of hydrogen peroxide is well known. In recent years, the
      presence of a novel group of enzymes, mainly involved in the metabolism of oxygen
      free-radicals, has been shown in peroxisomes. In addition to hydrogen peroxide,
      peroxisomes can generate superoxide-radicals and nitric oxide, which are known
      cellular messengers with a variety of physiological roles in intra- and inter
      cellular communication. Nitric oxide and hydrogen peroxide can permeate the
      peroxisomal membrane and superoxide radicals can be produced on the cytosolic
      side of the membrane. The signal molecule-generating capacity of peroxisomes can
      have important implications for cellular metabolism in plants, particularly under
      biotic and abiotic stress.

PMID- 11286919
TI  - Was the evolution of plastid genetic machinery discontinuous?
AB  - The plastid nucleoid consists of plastid DNA and various, mostly uncharacterized,
      DNA-binding proteins. The plastid DNA undoubtedly originated from an ancestral
      cyanobacterial genome, but the origin of the nucleoid proteins appears complex.
      Initial biochemical analysis of these proteins, as well as comparative genome
      informatics, suggest that proteins of eukaryotic origin replaced most of the
      original prokaryotic proteins during the evolution of plastids in the lineage of
      green plants.

PMID- 11286920
TI  - Controlling transgene integration in plants.
AB  - The creation of transgenic plants has brought significant advances to light in
      plant biotechnology. However, in spite of the fact that transgenic plants are
      beginning to be grown widely, controlled transgene integration into a pre
      determined site remains to be achieved. Here we suggest two alternative
      approaches for gene targeting in plants: manipulating the host and donor
      sequence, and targeting during active homologous recombination stages.

PMID- 11286921
TI  - Mobile factories: Golgi dynamics in plant cells.
AB  - The plant Golgi apparatus plays a central role in the synthesis of cell wall
      material and the modification and sorting of proteins destined for the cell
      surface and vacuoles. Earlier perceptions of this organelle were shaped by static
      transmission electron micrographs and by its biosynthetic functions. However, it
      has become increasingly clear that many Golgi activities can only be understood
      in the context of its dynamic organization. Significant new insights have been
      gained recently into the molecules that mediate this dynamic behavior, and how
      this machinery differs between plants and animals or yeast. Most notable is the
      discovery that plant Golgi stacks can actively move through the cytoplasm along
      actin filaments, an observation that has major implications for trafficking to,
      through and from this organelle.

PMID- 11286922
TI  - The glycine decarboxylase system: a fascinating complex.
AB  - The mitochondrial glycine decarboxylase multienzyme system, connected to serine
      hydroxymethyltransferase through a soluble pool of tetrahydrofolate, consists of
      four different component enzymes, the P-, H-, T- and L-proteins. In a multi-step
      reaction, it catalyses the rapid destruction of glycine molecules flooding out of
      the peroxisomes during the course of photorespiration. In green leaves, this
      multienzyme system is present at tremendously high concentrations within the
      mitochondrial matrix. The structure, mechanism and biogenesis of glycine
      decarboxylase are discussed. In the catalytic cycle of glycine decarboxylase,
      emphasis is given to the lipoate-dependent H-protein that plays a pivotal role,
      acting as a mobile substrate that commutes successively between the other three
      proteins. Plant mitochondria possess all the necessary enzymatic equipment for de
      novo synthesis of tetrahydrofolate and lipoic acid, serving as cofactors for
      glycine decarboxylase and serine hydroxymethyltransferase functioning.

PMID- 11286923
TI  - Nitric oxide: comparative synthesis and signaling in animal and plant cells.
AB  - Since its identification as an endothelium-derived relaxing factor in the 1980s,
      nitric oxide has become the source of intensive and exciting research in animals.
      Nitric oxide is now considered to be a widespread signaling molecule involved in
      the regulation of an impressive spectrum of mammalian cellular functions. Its
      diverse effects have been attributed to an ability to chemically react with
      dioxygen and its redox forms and with specific iron- and thiol-containing
      proteins. Moreover, the effects of nitric oxide are dependent on the dynamic
      regulation of its biosynthetic enzyme nitric oxide synthase. Recently, the role
      of nitric oxide in plants has received much attention. Plants not only respond to
      atmospheric nitric oxide, but also possess the capacity to produce nitric oxide
      enzymatically. Initial investigations into nitric oxide functions suggested that
      plants use nitric oxide as a signaling molecule via pathways remarkably similar
      to those found in mammals. These findings complement an emerging body of evidence
      indicating that many signal transduction pathways are shared between plants and
      animals.

PMID- 11286924
TI  - Life and death in the JUNgle.
AB  - Experiments with transgenic and knockout mice have begun to elucidate distinct
      roles for the three members of the Jun family of transcription factors. Mice with
      tissue-specific loss of JunB develop a myeloproliferative disorder, emphasizing
      the important roles that Jun proteins play in regulating life and death decisions
      in disease.

PMID- 11286925
TI  - Three down and counting: the transformation of human mammary cells from normal to
      malignant in three steps.
AB  - An array of genetic mutations associated with human breast cancers has been
      identified. However, which specific combination of mutations permit normal cells
      to form breast cancer remains unknown. Elenbaas et al. recently described an
      experimental system for studying the genetic requirements for the development of
      breast cancer.

PMID- 11286930
TI  - Leukemia cells fall on their swords.

PMID- 11286926
TI  - Chimeric stem cells.
AB  - There is growing excitement over stem cell biology. It has stirred strong ethical
      and moral debates over the status and rights of small clusters of cells. It has
      promised a panacea for illnesses ranging from diabetes to stroke. It has
      challenged historical dogmas in developmental biology. There have been many
      commentaries on all of these issues in prominent journals and newspapers over
      recent months. In this article, we take a critical look at new data that underpin
      the last of these claims: the chimeric stem cell.

PMID- 11286931
TI  - CFTR crystals.

PMID- 11286932
TI  - Tamoxifen is good for the heart.

PMID- 11286933
TI  - Stopping the flu.

PMID- 11286934
TI  - Step back and look at the forest.

PMID- 11286937
TI  - Stemming stroke-damaged brains.

PMID- 11286938
TI  - A "two-hit" model of cystogenesis in autosomal dominant polycystic kidney
      disease?
AB  - An intriguing feature of autosomal dominant polycystic kidney disease (ADPKD) is
      the focal and sporadic nature of individual cyst formation. Typically, only a few
      renal cysts are detectable in an affected individual during the first two decades
      of life. By the fifth decade, however, hundreds to thousands of renal cysts can
      be found in most patients. Additionally, significant intra-familial variability
      of ADPKD has been well documented. Taken together, these findings suggest that
      factor(s) in addition to the germline mutation of a polycystic kidney disease
      gene might be required for individual cyst formation. Indeed, recent studies have
      provided compelling evidence in support of a "two-hit" model of cystogenesis in
      ADPKD. In this model, inactivation of both copies of a polycystic kidney disease
      gene by germline and somatic mutations within an epithelial cell provides growth
      advantages for it to proliferate clonally into a cyst. This article highlights
      key findings of these recent studies and discusses the controversies and
      implications of the "two-hit" model in ADPKD.

PMID- 11286939
TI  - Tumorigenesis in neurofibromatosis: new insights and potential therapies.
AB  - The neurofibromatoses NF1 and NF2 are inherited cancer predisposition syndromes
      in which affected individuals are prone to development of mostly benign, but
      occasionally malignant, tumors. The NF1 and NF2 genes function as tumor
      suppressor genes (negative growth regulators), such that their loss of expression
      predisposes to tumor formation. Neurofibromin, the protein product of the NF1
      gene, acts as a negative regulator of the ras proto-oncogene, to reduce cell
      growth. Merlin, the NF2 gene product, is involved in regulating cell
      proliferation and motility, and probably plays a role in integrating multiple
      cell-signaling pathways. By understanding the function of these tumor
      suppressors, we have a unique opportunity to develop targeted pharmacotherapeutic
      interventions for these disorders.

PMID- 11286940
TI  - Oocyte activation: lessons from human infertility.
AB  - During fertilization, the spermatozoon penetrates through the cumulus cells and
      the zona pellucida that surrounds the oocyte, before it binds and fuses with the
      oocyte plasma membrane to induce activation. In vitro fertilization (IVF) studies
      performed in non-human mammals have contributed extensive knowledge regarding the
      mechanisms by which the spermatozoon activates the meiotic-arrested oocyte to
      resume meiosis, cleave and develop into an embryo. Although IVF has been used
      extensively for treating subfertile couples, not all of them were able to benefit
      from this procedure. In intracytoplasmic sperm injection (ICSI), one viable
      spermatozoon only is sufficient for successful fertilization of a single oocyte.
      Moreover, the injected fertilizing spermatozoon bypasses several physiological
      barriers, compared with IVF, which together could explain the high success rate
      for this procedure. ICSI has also allowed the identification of sperm components
      that are required for successful fertilization.

PMID- 11286941
TI  - Searching for schizophrenia genes.
AB  - Schizophrenia is characterized by profound disturbances of cognition, emotion and
      social functioning. It carries a lifetime risk within the general population of
      approximately 1%. Genetic epidemiological studies have shown that the syndrome
      has a high heritability, indicating a significant genetic component to its
      aetiology. However, the undoubted complexity and probable heterogeneity of the
      disorder continue to confound research, and the precise underlying
      neurobiological mechanisms remain largely unknown. Although molecular-genetic
      approaches face formidable difficulties, the identification of susceptibility
      genes is likely to provide valuable insights into the aetiology and pathogenesis
      that could lead to the development of more effective treatments.

PMID- 11286942
TI  - DNA-based vaccines for the treatment of cancer--an experimental model.
AB  - Antigenic differences between normal and malignant cells form the basis of
      clinical immunotherapy protocols. Because the antigenic phenotype varies widely
      among different cells within the same tumor mass, immunization with a vaccine
      that stimulates immunity to a broad array of tumor antigens expressed by the
      entire population of malignant cells is likely to be more efficacious than
      immunization with a vaccine for a single antigen. One strategy is to prepare a
      vaccine by transfer of DNA from the patient's tumor into a highly immunogenic
      cell line. Weak tumor antigens, characteristic of malignant cells, become
      strongly antigenic if they are expressed by immunogenic cells. In animal models
      of melanoma and breast cancer, immunization with a DNA-based vaccine is
      sufficient to deter tumor growth and to prolong the lives of tumor-bearing mice.

PMID- 11286943
TI  - Disease model: human aging.
AB  - Very little is known about the molecular mechanisms of human aging. This, at
      least in part, derives from a paucity of appropriate animal models of aging.
      Until recently, the senescence-accelerated mouse was the only mammalian model of
      aging. However, novel mouse models that exhibit multiple aging phenotypes have
      been developed in the past few years by disruption of the klotho gene, the
      telomerase gene and the genes involved in premature aging syndromes. These mouse
      models are expected to be important tools for aging research.

PMID- 11286944
TI  - Patient advocacy organizations partner genetic research, and forge the agenda.

PMID- 11286945
TI  - Pictures in Molecular Medicine: Telomeres copying telomeres in human cells.

PMID- 11286946
TI  - Physician interpretation of electrocardiographic artifact that mimics ventricular
      tachycardia.
AB  - BACKGROUND: Patients who are misdiagnosed with ventricular tachycardia because of
      electrocardiographic artifact may be subjected to unnecessary procedures. The
      purpose of this study was to determine how often electrocardiographic artifact is
      misdiagnosed as ventricular tachycardia. METHODS: Physicians (n = 766) were
      surveyed with a case simulation that included a two-lead electrocardiographic
      monitor tracing of artifact simulating a wide-complex tachycardia. RESULTS: The
      rhythm strip was not recognized as artifact by 52 of the 55 internists (94%), 128
      of the 221 cardiologists (58%), and 186 of the 490 electrophysiologists (38%).
      One hundred fifty-six of the 181 electrophysiologists (88%), 67 of the 126
      cardiologists (53%), and 14 of the 15 internists (31%) who misdiagnosed the
      rhythm as ventricular tachycardia recommended an invasive procedure for further
      evaluation or therapy. CONCLUSIONS: This physician survey suggests that
      electrocardiographic artifact that mimics ventricular tachycardia may frequently
      result in patients being subjected to unnecessary invasive cardiac procedures.
      Physicians should include artifact in their differential diagnosis of wide
      complex tachycardias to minimize unneeded procedures.

PMID- 11286947
TI  - Equivalent outcomes in patients with chronic myelogenous leukemia after early
      transplantation of phenotypically matched bone marrow from related or unrelated
      donors.
AB  - PURPOSE: To determine if the favorable outcomes after transplantation of matched
      sibling donor bone marrow in patients with chronic myelogenous leukemia can be
      achieved using bone marrow from an HLA-A,B/DRB1-matched unrelated donor. SUBJECTS
      AND METHODS: Between April 1983 and December 1997, 141 patients with chronic
      myelogenous leukemia in its first chronic phase received a bone marrow transplant
      from a matched sibling donor (n = 96) or an HLA-A,B/DRB1-matched unrelated donor
      (n = 45). The median age of matched sibling donor recipients was 38 years (range,
      8 to 56 years) and of unrelated donor recipients was 35 years (range, 3 to 53
      years; P = 0.03). The median follow-up was 6 years (range, 1 to 15 years) in
      matched sibling donor recipients and 5 years (range, 2 to 10 years) in unrelated
      donor recipients. RESULTS: There was no significant difference in the 5-year
      survival rates of matched sibling donor recipients [58%; 95% confidence interval
      (CI), 48% to 68%] and unrelated donor recipients (53%; 95% CI, 39% to 67%; P =
      0.4). Among patients who underwent transplantation within 1 year after diagnosis,
      the 5-year survival rate of matched sibling donor recipients (76%; 95% CI, 65% to
      87%) was not significantly different (P = 0.5) from that of unrelated donor
      recipients (70%; 95% CI, 52% to 88%). In multiple regression analysis, longer
      time from diagnosis to transplantation, T-cell depletion, and grades III or IV
      graft versus host disease were independently associated with poorer survival.
      Transplantation of unrelated donor bone marrow was not associated with mortality
      (relative risk, 1.1; 95% CI, 0.6 to 2.1; P = 0.7). CONCLUSIONS: Transplantation
      of bone marrow from a matched sibling donor or an HLA-A,B/DRB1-matched unrelated
      donor produces equivalent outcomes in patients with chronic myelogenous leukemia,
      particularly if the transplant takes place within 1 year after diagnosis.

PMID- 11286948
TI  - Declining rate of substance abuse throughout the month.
AB  - PURPOSE: The timing of federal disbursements of welfare, disability, and military
      benefits may be associated with monthly patterns of substance abuse. We assessed
      whether this association was reflected in the pattern of psychiatric
      presentations to an emergency room. SUBJECTS AND METHODS: We conducted a
      retrospective, case-control study of 12,904 patient presentations to an urban
      emergency department for psychiatric reasons during a 7-year period. Cases were
      defined as patients (n = 2,403) given a primary diagnosis of substance abuse.
      Controls included patients (n = 10,501) with a primary diagnosis of another
      psychiatric illness. We calculated the "boundary effect" (R = 100 times the
      number of presentations during the first week of the month divided by number of
      presentations during the last week of the preceding month) for each month, and
      averaged these values across months to determine overall effects. RESULTS: The
      boundary effect was stronger for patients with primary substance abuse disorders
      (R = 134, 95% confidence interval [CI] = 118 to 151) than for patients with other
      psychiatric disorders (R = 106, 95% CI = 100 to 112; P < 0.001). Weekly
      presentations for substance abuse declined consistently throughout the month (P =
      0.01), and declined significantly more than the incidence of other psychiatric
      presentations (P = 0.005). These effects remained, after adjusting for
      fluctuations in presentations around holidays and the new year. The lunar cycle
      did not influence the incidence of presentations. CONCLUSION: Our results confirm
      that substance-related morbidity is highest at the beginning of the month and
      declines thereafter, corresponding to the availability of disposable income from
      monthly checks.

PMID- 11286949
TI  - Efficacy and safety of combination simvastatin and colesevelam in patients with
      primary hypercholesterolemia.
AB  - PURPOSE: To examine the efficacy and safety of colesevelam hydrochloride, a
      novel, nonsystemic, lipid-lowering agent, when coadministered with starting doses
      of simvastatin in a multicenter, randomized, double-blind, placebo-controlled
      trial. PATIENTS AND METHODS: Subjects with hypercholesterolemia (plasma low
      density lipoprotein [LDL] cholesterol level > 160 mg/dL and triglyceride level <
      or = 300 mg/dL) were randomly assigned to receive daily doses of placebo (n =
      33), colesevelam 3.8 g (recommended dose, n = 37), simvastatin 10 mg (n = 35),
      colesevelam 3.8 g with simvastatin 10 mg (n = 34), colesevelam 2.3 g (low dose, n
      = 36), simvastatin 20 mg (n = 39), or colesevelam 2.3 g with simvastatin 20 mg (n
      = 37), for 6 weeks. RESULTS: Mean LDL cholesterol levels decreased relative to
      baseline in the placebo group (P < 0.05) and in all active treatment groups (P <
      0.0001). For groups treated with combination therapy, the mean reduction in LDL
      cholesterol level was 42% (-80 mg/dL; P < 0.0001 compared with baseline), which
      exceeded the reductions for simvastatin 10 mg (-26%, -48 mg/dL) or 20 mg (-34%, 
      61 mg/dL) alone, or for colesevelam 2.3 g (-8%, -17 mg/dL) or 3.8 g (-16%, -31
      mg/dL) alone (P < 0.001). The effects of combination therapy on serum HDL
      cholesterol and triglyceride levels were similar to those for simvastatin alone.
      Side effects were similar among treatment groups, and there were no clinically
      important changes in laboratory parameters. CONCLUSION: Coadministration of
      colesevelam and simvastatin was effective and well tolerated, providing additive
      reductions in LDL cholesterol levels compared with either agent alone.

PMID- 11286950
TI  - Prognostic value of pharmacologic stress echocardiography in patients with left
      bundle branch block.
AB  - PURPOSE: Although coronary artery disease is a frequent cause of left bundle
      branch block, the prognostic value of myocardial ischemia in patients with this
      conduction abnormality has not been defined. We investigated the value of
      pharmacologic stress echocardiography in risk stratification of patients with
      left bundle branch block. PATIENTS AND METHODS: Three hundred eighty-seven
      patients [230 men and 157 women, mean (+/- SD) age, 64 +/- 9 years] with complete
      left bundle branch block on the resting electrocardiogram underwent dobutamine (n
      = 217) or dipyridamole (n = 170) stress echocardiography to evaluate suspected or
      known coronary artery disease. A summary wall motion score (on a one to four
      scale) was calculated. The primary end points were cardiac death and nonfatal
      myocardial infarction. RESULTS: A positive echocardiographic result (evidence of
      ischemia) was detected in 109 (28%) patients. During a mean follow-up of 29 +/-
      26 months, there were 21 cardiac deaths and 20 myocardial infarctions, 63
      patients underwent coronary revascularization, and 1 patient received a heart
      transplant. In a multivariate analysis, four clinical and echocardiographic
      variables were associated with increased risk of cardiac death: resting wall
      motion score index [hazard ratio (HR) = 7.5 per unit; 95% confidence interval
      (CI), 2.8 to 20; P = 0.001], previous myocardial infarction (HR = 2.9; 95% CI,
      1.1 to 7.3; P = 0.02), diabetes (HR = 2.7; 95% CI, 1.1 to 6.6; P = 0.03), and the
      change in wall motion score index from rest to peak stress (HR = 3.0 per unit;
      95% CI, 1.0 to 8.6; P = 0.04). The 5-year survival was 77% in the ischemic group
      and 92% in the nonischemic group (P = 0.02). Four variables were associated with
      increased risk of cardiac death or infarction: previous myocardial infarction (HR
      = 3.4; 95% CI, 1.7 to 6.8; P = 0.0005), diabetes (HR = 2.4; 95% CI, 1.2 to 4.6; P
      = 0.01), resting wall motion score index (HR = 2.2 per unit; 95% CI, 1.1 to 4.1;
      P = 0.02), and positive echocardiographic result (HR = 2.2; 95% CI, 1.1 to 4.5; P
      = 0.03). The 5-year infarction-free survival was 60% in the ischemic group and
      87% in the nonischemic group (P < 0.0001). Stress echocardiography significantly
      improved risk stratification in patients without previous myocardial infarction
      (P = 0.0001), but not in those with previous myocardial infarction (P = 0.08). In
      particular, it provided additional value over clinical and resting
      echocardiographic findings in predicting cardiac events among patients without
      previous infarction. CONCLUSIONS: Myocardial ischemia during pharmacologic stress
      echocardiography is a strong prognostic predictor in patients with left bundle
      branch block, particularly in those without previous myocardial infarction.

PMID- 11286951
TI  - Electronic publishing of science: better late than never.
AB  - The time required for medical publication in the print literature has changed
      little in 200 years, whereas scientific discovery now proceeds at a dizzying
      pace. There is a growing disjunction between the efficiency of science and the
      inefficiency of scientific reporting. Electronic publication as proposed for
      PubMedCentral is a logical solution to this problem.

PMID- 11286952
TI  - Physician opinion about electronic publications.
AB  - PURPOSE: Many medical journals are currently offering physicians the option to
      subscribe electronically, allowing readers access by means of the Internet.
      However, physicians' opinions about this innovation are not known. This
      exploratory study was designed to learn more about physicians' opinions and
      attitudes regarding electronic publications. SUBJECTS AND METHODS: A three-page
      questionnaire was developed to survey all physicians (faculty and house officers)
      at a large university-affiliated teaching hospital in Baltimore, Maryland. The
      questionnaire explored many of the features that make electronic journals
      distinct from printed journals. RESULTS: Of the 314 physicians surveyed, 255
      (81%) returned a completed questionnaire. The mean (+/- SD) age of the
      respondents was 41 +/- 10 years, 164 (65%) were male, and 50 (20%) were house
      officers. Twenty-six percent of respondents (n = 66) thought that electronic
      journals would lower the quality of the medical literature, and 25% (n = 63)
      believed that the prestige of authorship would be lessened. Seventy to eighty
      percent of physicians responded that electronic journals would decrease clutter
      in their offices and homes, be more environmentally friendly than the current
      system, make it easier to locate research reports that they had read, and offer
      the benefit of linkage to related articles. Seventy-four percent of physicians (n
      = 188) were concerned about losing the convenience of being able to read a
      printed journal anywhere. In multivariate analyses, female sex, being a faculty
      member (vs house officer), fewer publications, better computer skills, and more
      frequent use of the Internet were independently associated with positive
      attitudes toward various aspects of electronic journals. CONCLUSIONS: Physicians
      responded favorably to the many potential values and applications of electronic
      publications but were most concerned with the loss of the convenience that
      printed journals offer.

PMID- 11286953
TI  - A systematic review of randomized trials of disease management programs in heart
      failure.
AB  - PURPOSE: Disease management programs are often advocated for the care of patients
      with chronic disease. This systematic review was conducted to determine whether
      these programs improve outcomes for patients with heart failure. METHODS:
      Randomized clinical trials of disease management programs in patients with heart
      failure were identified by searching Medline 1966 to 1999, Embase 1980 to 1998,
      Cinahl 1982 to 1999, Sigle 1980 to 1998, the Cochrane Controlled Trial Registry,
      the Cochrane Effective Practice and Organization of Care Study Registry, and the
      bibliographies of published studies. We also contacted experts in the field.
      Studies were selected and data extracted independently by two investigators, and
      summary risk ratios (RR) and 95% confidence intervals (CI) were calculated using
      both the random and fixed effects models. RESULTS: A total of 11 trials
      (involving 2,067 patients with heart failure) were identified. Disease management
      programs were cost saving in 7 of the 8 trials that reported cost data and also
      appeared to have beneficial effects on prescribing practices. Hospitalizations
      (RR = 0.87, 95% CI: 0.79 to 0.96) but not all-cause mortality (RR = 0.94, 95% CI:
      0.75 to 1.19) were reduced by the programs. However, there were considerable
      differences in the effects of various interventions on hospitalization rates;
      specialized follow-up by a multidisciplinary team led to a substantial reduction
      in the risk of hospitalization (RR = 0.77, 95% CI 0.68 to 0.86, n = 1366),
      whereas trials employing telephone contact with improved coordination of primary
      care services failed to find any benefit (RR = 1.15, 95% CI 0.96 to 1.37, n =
      646). CONCLUSION: Disease management programs for the care of patients with heart
      failure that involve specialized follow-up by a multidisciplinary team reduce
      hospitalizations and appear to be cost saving. Data on mortality are
      inconclusive. Further studies are needed to establish the incremental benefits of
      the different elements of these programs.

PMID- 11286954
TI  - Molecular biology and the prolonged QT syndromes.
AB  - The prolonged QT syndromes are characterized by prolongation of the QT interval
      corrected for heart rate (QTc) on the surface electrocardiogram associated with T
      wave abnormalities, relative bradycardia, and ventricular tachyarrhythmias,
      including polymorphic ventricular tachycardia and torsades de pointes. These
      patients tend to present with episodes of syncope, seizures, or sudden death
      typically triggered by exercise, emotion, noise, or, in some cases, sleep. These
      disorders of cardiac repolarization are commonly inherited, with the autosomal
      dominant form, Romano-Ward syndrome, most common. A rare autosomal recessive form
      associated with sensorineural deafness, Jervell and Lange-Nielsen syndrome, in
      which the cardiac disorder is autosomal dominant and deafness is a recessive
      trait, also occurs. The underlying genetic causes of these forms of prolonged QT
      interval syndromes are heterogeneous, with at least seven genes responsible for
      the clinical syndromes. All of the five genes identified to date encode ion
      channel proteins, suggesting this to be an ion channelopathy. In this review, the
      genetic basis of the prolonged QT interval syndromes will be discussed, genotype
      phenotype correlations identified, and the approaches to genetic testing and
      treatments will be outlined.

PMID- 11286955
TI  - Guillain-Barre syndrome complicated with hemolytic anemia in association with
      antiganglioside GM3 antibody.

PMID- 11286957
TI  - Electrocardiography artifact: what you do not know, you do not recognize.

PMID- 11286958
TI  - Treatment of chronic myeloid leukemia.

PMID- 11286959
TI  - Relapse triggers-full moon, full wallet, or foolhardy?

PMID- 11286960
TI  - Publishing at the speed of life.

PMID- 11286961
TI  - Heart failure disease management programs: efficacy and limitations.

PMID- 11286962
TI  - Teaching students the art and science of physical diagnosis.

PMID- 11286963
TI  - Delipidated serum abolishes the inhibitory effect of serum on in vitro liposome
      mediated transfection.
AB  - All the standard in vitro lipofection has been routinely performed in serum-free
      medium as the transfection activity of liposome/DNA complexes is sensitive to the
      presence of serum. In this study, we have demonstrated that lipid-rich serum
      lipoprotein included in the transfection medium strongly inhibited the
      transfection activity of DC-chol liposome/DNA complexes in five different cell
      types (CHO, 293, A2780CP, A431 and SKBR3). The levels of inhibition by serum
      lipoprotein were rather greater than those by serum and varied with cell types.
      However, this inhibition was completely abolished by delipidation of serum. Thus,
      delipidated serum can be included in the transfection medium. The complexes
      formed in the presence of serum (zeta=-18.2+/-1.07 mV), delipidated serum (zeta=
      19.6+/-0.54 mV), IgG (zeta=-21.6+/-1.92 mV) or serum lipoprotein (zeta=-10.5+/
      2.33 mV) were as much negatively charged as those in serum-free medium (zeta=
      21.3+/-1.60 mV). The results suggest that the inhibition of liposome-mediated
      transfection by serum was not associated with charges of serum proteins but with
      lipids or lipid-associated proteins present in serum.

PMID- 11286964
TI  - Homologues of archaeal rhodopsins in plants, animals and fungi: structural and
      functional predications for a putative fungal chaperone protein.
AB  - The microbial rhodopsins (MR) are homologous to putative chaperone and retinal
      binding proteins of fungi. These proteins comprise a coherent family that we have
      termed the MR family. We have used modeling techniques to predict the structure
      of one of the putative yeast chaperone proteins, YRO2, based on homology with
      bacteriorhodopsins (BR). Availability of the structure allowed depiction of
      conserved residues that are likely to be of functional significance. The results
      lead us to predict an extracellular protein folding function and a transmembrane
      proton transport pathway. We suggest that protein folding is energized by a novel
      mechanism involving the proton motive force. We further show that MR family
      proteins are distantly related to a family of fungal, animal and plant proteins
      that include the human lysosomal cystine transporter (LCT) of man (cystinosin),
      mutations in which cause cystinosis. Sequence and phylogenetic analyses of both
      the MR family and the LCT family are reported. Proteins in both families are of
      the same approximate size, exhibit seven putative transmembrane alpha-helical
      spanners (TMSs) and show limited sequence similarity. We show that the LCT family
      arose by an internal gene duplication event and that TMSs 1-3 are homologous to
      TMSs 5-7. Although the same could not be demonstrated statistically for MR family
      members, homology with the LCT family suggests (but does not prove) a common
      evolutionary pathway. Thus, TMSs 1-3 and 5-7 in both LCT and MR family members
      may share a common origin, accounting for their shared structural features.

PMID- 11286966
TI  - Exclusion of a cholesterol analog from the cholesterol-rich phase in model
      membranes.
AB  - Vesicles of phosphatidylcholine/cholesterol mixtures show a wide composition
      range with coexistence of two fluid phases, the 'liquid disordered' (cholesterol
      poor) and 'liquid ordered' (cholesterol-rich) phases. These systems have been
      widely used as models of membranes exhibiting lateral heterogeneity (membrane
      domains). The distributions of two fluorescent probes (a fluorescent cholesterol
      analog, NBD-cholesterol, and a lipophilic rhodamine probe, octadecylrhodamine B)
      in dimyristoylphosphatidylcholine/cholesterol vesicles were studied, at 30
      degrees C and 40 degrees C. The steady-state fluorescence intensity of both
      probes decreases markedly with increasing cholesterol concentration, unlike the
      fluorescence lifetimes. The liquid ordered to liquid disordered phase partition
      coefficients K(p) were measured, and values much less than unity were obtained
      for both probes, pointing to preference for the cholesterol-poor phase. Globally
      analyzed time-resolved energy transfer results confirmed these findings. It is
      concluded that, in particular, NBD-cholesterol is not a suitable cholesterol
      analog and its distribution behavior in phosphatidylcholine/cholesterol bilayers
      is in fact opposite to that of cholesterol.

PMID- 11286965
TI  - Conformation and orientation of the gene 9 minor coat protein of bacteriophage
      M13 in phospholipid bilayers.
AB  - The membrane-bound state of the gene 9 minor coat protein of bacteriophage M13
      was studied in model membrane systems, which varied in lipid head group and lipid
      acyl chain composition. By using FTIR spectroscopy and subsequent band analysis a
      quantitative analysis of the secondary structure of the protein was obtained. The
      secondary structure of the gene 9 protein predominantly consists of alpha-helical
      (67%) and turn (33%) structures. The turn structure is likely to be located C
      terminally where it has a function in recognizing the phage DNA during
      bacteriophage assembly. Attenuated total reflection FTIR spectroscopy was used to
      determine the orientation of gene 9 protein in the membrane, revealing that the
      alpha-helical domain is mainly transmembrane. The conformational and
      orientational measurements result in two models for the gene 9 protein in the
      membrane: a single transmembrane helix model and a two-helix model consisting of
      a 15 amino acid long transmembrane helix and a 10 amino acid long helix oriented
      parallel to the membrane plane. Potential structural consequences for both models
      are discussed.

PMID- 11286967
TI  - The influence of two azones and sebaceous lipids on the lateral organization of
      lipids isolated from human stratum corneum.
AB  - The main problem with topical application of compounds to administer drugs to and
      regulate drug levels in a human body, is the barrier formed by the intercellular
      lipid matrix of the stratum corneum (SC). In a search for possibilities to
      overcome this barrier function, a good understanding of the organization and
      phase behavior of these lipids is required. SC lipid model studies especially
      provide a wealth of information with respect to the lipid organization and the
      importance of certain subclasses of lipids for the structure. Previously, we have
      shown that electron diffraction (ED) provides detailed information on the lateral
      lipid packing in both intact SC (G.S.K. Pilgram et al., J. Invest. Dermatol. 113
      (1999) 403) and SC lipid models (G.S.K. Pilgram et al., J. Lipid Res. 39 (1998)
      1669). In the present study, we used ED to examine the influence of two azones
      and sebaceous lipids on the lateral phase behavior of lipids isolated from human
      SC. We established that human SC lipids are arranged in an orthorhombic packing
      pattern. Upon mixing with the two enhancers the orthorhombic packing pattern was
      still observed; however, an additional fluid phase became more apparent. In
      mixtures with sebaceous lipids, the presence of the hexagonal lattice increased.
      These findings provide a basis for the mechanism by which these enhancers and
      sebaceous lipids interact with human SC lipids.

PMID- 11286968
TI  - Antifreeze proteins differentially affect model membranes during freezing.
AB  - Over the past decade antifreeze proteins from polar fish have been shown either
      to stabilize or disrupt membrane structure during low temperature and freezing
      stress. However, there has been no systematic study on how membrane composition
      affects the interaction of antifreeze proteins with membranes under stress
      conditions. Therefore, it is not possible at present to predict which antifreeze
      proteins will protect, and which will damage a particular membrane during
      chilling or freezing. Here, we analyze the effects of freezing on spinach
      thylakoid membranes and on model membranes of varying lipid composition in the
      presence of antifreeze protein type I (AFP I) and specific fractions of
      antifreeze glycoproteins (AFGP). We find that the addition of galactolipids to
      phospholipid model membranes changes the effect each protein has on the membrane
      during freezing. However, the greatest differences observed in this study are
      between the different types of antifreeze proteins. We find that AFP type I and
      the largest molecular weight fractions of AFGP induce concentration dependent
      leakage from, and are fusogenic to the liposomes. This is the first report that
      an antifreeze protein induces membrane fusion. In contrast, the smallest fraction
      of AFGP offers a limited degree of protection during freezing and does not induce
      membrane fusion at concentrations up to 10 mg/ml.

PMID- 11286969
TI  - Cholesterol stabilizes hemifused phospholipid bilayer vesicles.
AB  - Cholesterol was found to inhibit full fusion of oppositely charged phospholipid
      bilayer vesicles by stabilizing the contacting membranes at the stage of the
      hemifused intermediate. Vesicles of opposite charge containing different amounts
      of cholesterol were prepared using cationic (1,2-dioleoyl-sn-glycero-3
      ethylphosphocholine) and anionic (dioleoylphosphatidylglycerol) phospholipids.
      Pairwise interactions between such vesicles were observed by fluorescence video
      microscopy in real time after electrophoretically maneuvering the vesicles into
      contact. Hemifusion accounted for more than 80% of the observed events when the
      vesicles contained 33-50 mole% cholesterol. In contrast, vesicles containing only
      a small proportion of cholesterol (</=10 mole%), underwent full fusion in approx.
      70% of the interactions monitored. The role of cholesterol is explained both as
      favoring the formation of the hemifused intermediate according to the adhesion
      condensation mechanism of bilayer fusion and as disfavoring the transition from
      hemifusion to full fusion on the basis of reduced tension in the vesicle
      bilayers.

PMID- 11286970
TI  - Occurrence of gangliosides in the common squid and pacific octopus among
      protostomia.
AB  - Acidic lipids from tissues of the common squid Todarodes pacificus and the
      pacific octopus Octopus vulgaris were characterized. Hepatopancreatic tissues of
      both animals had complex compositions of resorcinol-positive acidic lipids, many
      of which became reactive with cholera toxin B subunit and anti-G(M1) antibody
      after in situ treatment with sialidase on TLC. One of the major acidic lipids in
      squid tissue was isolated and examined for its structure. This acidic lipid was
      identified to be the ganglioside G(D1a) based upon the susceptibility to
      sialidases of different substrate specificity, characterization of reaction
      products, and electrospray ionization-mass spectrometry of the lipid.
      Hepatopancreatic tissues of squid and octopus also contained acidic lipids that
      reacted with A2B5, a monoclonal antibody specific to c-series gangliosides.
      Cerebral ganglia of both animals expressed resorcinol-positive acidic lipids,
      though their compositional patterns differed from the hepatopancreatic tissues. N
      Acetylneuraminic acid was identified as the main species in lipid-bound sialic
      acid in both tissues. The contents of lipid-bound sialic acid in cerebral ganglia
      were significantly lower than those of hepatopancreatic tissues in both animals.
      The present study presents the first evidence for the occurrence of gangliosides
      in protostomia.

PMID- 11286971
TI  - Effects of (+)-totarol, a diterpenoid antibacterial agent, on phospholipid model
      membranes.
AB  - (+)-Totarol, a highly hydrophobic diterpenoid isolated from Podocarpus spp., is
      inhibitory towards the growth of diverse bacterial species. (+)-Totarol decreased
      the onset temperature of the gel to liquid-crystalline phase transition of DMPC
      and DMPG membranes and was immiscible with these lipids in the fluid phase at
      concentrations greater than 5 mol%. Different (+)-totarol/phospholipid mixtures
      having different stoichiometries appear to coexist with the pure phospholipid in
      the fluid phase. At concentrations greater than 15 mol% (+)-totarol completely
      suppressed the gel to liquid-crystalline phase transition in both DMPC and DMPG
      vesicles. Incorporation of increasing amounts of (+)-totarol into DEPE vesicles
      induced the appearance of the H(II) hexagonal phase at low temperatures in
      accordance with NMR data. At (+)-totarol concentrations between 5 and 35 mol%
      complex thermograms were observed, with new immiscible phases appearing at
      temperatures below the main transition of DEPE. Steady-state fluorescence
      anisotropy measurements showed that (+)-totarol decreased and increased the
      structural order of the phospholipid bilayer below and above the main gel to
      liquid-crystalline phase transition of DMPC respectively. The changes that (+)
      totarol promotes in the physical properties of model membranes, compromising the
      functional integrity of the cell membrane, could explain its antibacterial
      effects.

PMID- 11286972
TI  - Specific heat determination of plant barrier lipophilic components: biological
      implications.
AB  - The specific heat of isolated plant cuticles and their corresponding cuticular
      waxes have been measured for the physiological temperature in the range of 273
      318 K at regular intervals. C(p) values ranged from 1.5 up to 4 J K(-1) g(-1)
      indicating a high cohesion, at the molecular level, of the molecular lipophilic
      components that constitute the plant cuticle. Second order phase transitions
      around 293 K, assigned to the cuticular matrix mainly constituted of the
      biopolyester cutin, have been detected and measured. Ecophysiological and
      physical implications of these thermodynamic data are discussed.

PMID- 11286973
TI  - Thermal transitions of DMPG bilayers in aqueous solution: SAXS structural
      studies.
AB  - Dimyristoylphosphatidylglycerol (DMPG) has been extensively studied as a model
      for biological membranes, since phosphatidylglycerol is the most abundant anionic
      phospholipid in prokaryotic cells. At low ionic strengths, this lipid presents a
      peculiar thermal behavior, with two sharp changes in the light scattering
      profile, at temperatures named here T(on)(m) and T(off)(m). Structural changes
      involved in the DMPG thermal transitions are here investigated by small angle X
      ray scattering (SAXS), and compared to the results yielded by differential
      scanning calorimetry (DSC) and electron spin resonance (ESR). The SAXS results
      show a broad peak, indicating that DMPG is organized in single bilayers, for the
      range of temperature studied (10-45 degrees C). SAXS intensity shows an unusual
      effect, starting to decrease at T(on)(m), and presenting a sharp increase at
      T(off)(m). The bilayer electron density profiles, obtained from modeling the SAXS
      curves, show a gradual decrease in electron density contrast (attributed to
      separation between charged head groups) and in bilayer thickness between T(on)(m)
      and T(off)(m). Results yielded by SAXS, DSC and ESR indicate that a chain melting
      process starts at T(on)(m), but a complete fluid phase exists only for
      temperatures above T(off)(m), with structural changes occurring at the bilayer
      level in the intermediate region.

PMID- 11286974
TI  - Spontaneous insertion of gene 9 minor coat protein of bacteriophage M13 in model
      membranes.
AB  - Gene 9 minor coat protein from bacteriophage M13 is known to be located in the
      inner membrane after phage infection of Escherichia coli. The way of insertion of
      this small protein (32 amino acids) into membranes is still unknown. Here we show
      that the protein is able to insert in monolayers. The limiting surface pressure
      of 35 mN/m for 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn
      glycero-3-phosphoglycerol lipid systems indicates that this spontaneous insertion
      can also occur in vivo. By carboxyfluorescein leakage experiments of vesicles it
      is demonstrated that protein monomers, or at least small aggregates, are more
      effective in releasing carboxyfluorescein than highly aggregated protein. The
      final orientation of the protein in the bilayer after insertion was addressed by
      proteinase K digestion, thereby making use of the unique C-terminal location of
      the antigenic binding site. After insertion the C-terminus is still available for
      the enzymatic digestion, while the N-terminus is not. This leads to the overall
      conclusion that the protein is able to insert spontaneously into membranes
      without the need of any machinery or transmembrane gradient, with the positively
      charged C-terminus remaining on the outside. The orientation after insertion of
      gene 9 protein is in agreement with the 'positive inside rule'.

PMID- 11286975
TI  - The carboxyl terminus of Dictyostelium discoideum protein 1I encodes a functional
      glycosyl-phosphatidylinositol signal sequence.
AB  - The 1I gene is expressed in the prespore cells of culminating Dictyostelium
      discoideum. The open reading frame of 1I cDNA encodes a protein of 155 amino
      acids with hydrophobic segments at both its NH(2)- and COOH-termini that are
      indicative of a glycosyl-phosphatidylinositol (GPI)-anchored protein. A hexaHis
      tagged form of 1I expressed in D. discoideum cells appeared on Western blot
      analysis as a doublet of 27 and 24 kDa, with a minor polypeptide of 22 kDa. None
      of the polypeptides were released from the cell surface with bacterial
      phosphatidylinositol-specific phospholipase C, although all three were released
      upon nitrous acid treatment, indicating the presence of a phospholipase-resistant
      GPI anchor. Further evidence for the C-terminal sequence of 1I acting as a GPI
      attachment signal was obtained by replacing the GPI anchor signal sequence of
      porcine membrane dipeptidase with that from 1I. Two constructs of dipeptidase
      with the 1I GPI signal sequence were constructed, one of which included an
      additional six amino acids in the hydrophilic spacer. Both of the resultant
      constructs were targeted to the surface of COS cells and were GPI-anchored as
      shown by digestion with phospholipase C, indicating that the Dictyostelium GPI
      signal sequence is functional in mammalian cells. Site-specific antibodies
      recognising epitopes either side of the expected GPI anchor attachment site were
      used to determine the site of GPI anchor attachment in the constructs. These
      parallel approaches show that the C-terminal signal sequence of 1I can direct the
      addition of a GPI anchor.

PMID- 11286976
TI  - Surface properties of cholesterol-containing membranes detected by Prodan
      fluorescence.
AB  - The fluorescent membrane probe 6-propionyl-2-dimethylaminonaphthalene (Prodan)
      displays a high sensitivity to the polarity and packing properties of lipid
      membrane. Contrary to 6-lauroyl-2-dimethylaminonaphthalene (Laurdan), Prodan can
      also monitor the properties of the membrane surface, i.e., the polar-head
      pretransition. In bilayers composed of coexisting gel and liquid-crystalline
      phases, Prodan shows a preferential partitioning in the latter, so that the
      detected membrane properties mainly belong to fluid domains. In the presence of
      cholesterol, the packing properties of the gel phase phospholipids are modified
      in such a way that Prodan can penetrate and label the membrane. Although Prodan
      labeling of the gel phase is a function of cholesterol concentration, 3 mol
      percent cholesterol is sufficient for a 60% Prodan labeling with respect to the
      maximum labeling reached at 15 mol percent cholesterol. We present steady-state
      and dynamical fluorescence measurements of Prodan in bilayers in the presence of
      cholesterol. Our results fit the liquid-ordered/liquid-disordered phase model for
      cholesterol-containing membranes and show that the presence of cholesterol, in
      addition to modification to the phase state of the hydrophobic portion of the
      bilayer, strongly affects the packing and the polarity of the membrane
      hydrophobic-hydrophilic interface.

PMID- 11286977
TI  - Comparative behavior of sterols in phosphatidylcholine-sterol monolayer films.
AB  - The ability of sterols other than cholesterol (CHOL) to support membrane
      functions in membranes that normally contain CHOL as the primary, if not sole,
      sterol may be due, in part, to how well such sterols can mimic CHOL's behavior
      and physical properties in membranes. We compared the mixing properties of CHOL,
      7-dehydrocholesterol (7DHC), and desmosterol (DES) in egg phosphatidylcholine
      sterol monolayer films containing 10, 20, and 30 mol percent sterol, measuring
      pressure-area isotherms on a Langmuir-Blodgett trough with the aqueous, buffered
      subphase maintained at 37 degrees C. Under the conditions employed, the pressure
      area isotherms for all three sterols were similar, with 7DHC exhibiting slightly
      larger molecular areas on the water surface at all compositions. These results
      are discussed in the context of the ability of sterols such as 7DHC and DES to
      substitute structurally and functionally for CHOL in biological membranes.

PMID- 11286978
TI  - Transport of aspartic acid, arginine, and tyrosine by the opportunistic protist
      Pneumocystis carinii.
AB  - In order to improve culture media and to discover potential drug targets, uptake
      of an acidic, a basic, and an aromatic amino acid were investigated. Current
      culture systems, axenic or co-cultivation with mammalian cells, do not provide
      either the quantity or quality of cells needed for biochemical studies of this
      organism. Insight into nutrient acquisition can be expected to lead to improved
      culture media and improved culture growth. Aspartic acid uptake was directly
      related to substrate concentration, Q(10) was 1.10 at pH 7.4. Hence the organism
      acquired this acidic amino acid by simple diffusion. Uptake of the basic amino
      acid arginine and the aromatic amino acid tyrosine exhibited saturation kinetics
      consistent with carrier-mediated mechanisms. Kinetic parameters indicated two
      carriers (K(m)=22.8+/-2.5 microM and K(m)=3.6+/-0.3 mM) for arginine and a single
      carrier for tyrosine (K(m)=284+/-23 microM). The effects of other L-amino acids
      showed that the tyrosine carrier was distinct from the arginine carriers.
      Tyrosine and arginine transport were independent of sodium and potassium ions,
      and did not appear to require energy from ATP or a proton motive force. Thus
      facilitated diffusion was identified as the mechanism of uptake. After 30 min of
      incubation, these amino acids were incorporated into total lipids and the
      sedimentable material following lipid extraction; more than 90% was in the
      cellular soluble fraction.

PMID- 11286979
TI  - Changes induced by malathion, methylparathion and parathion on membrane lipid
      physicochemical properties correlate with their toxicity.
AB  - Perturbations induced by malathion, methylparathion and parathion on the
      physicochemical properties of dipalmitoylphosphatidylcholine (DPPC) were studied
      by fluorescence anisotropy of DPH and DPH-PA and by differential scanning
      calorimetry (DSC). Methylparathion and parathion (50 microM) increased the
      fluorescence anisotropy evaluated by DPH-PA and DPH, either in gel or in the
      fluid phase of DPPC bilayers, but mainly in the fluid phase. Parathion is more
      effective than methylparathion. On the other hand, malathion had almost no
      effect. All the three xenobiotics displaced the phase transition midpoint to
      lower temperature values and broadened the phase transition profile of DPPC, the
      effectiveness following the sequence: parathion>methylparathion>>malathion. A
      shifting and broadening of the phase transition was also observed by DSC.
      Furthermore, at methylparathion/lipid molar ratio of 1/2 and at parathion/lipid
      molar ratio of 1/7, the DSC thermograms displayed a shoulder in the main peak, in
      the low temperature side, suggesting coexistence of phases. For higher ratios,
      the phase transition profile becomes sharp as the control transition, but the
      midpoint is shifted to the previous shoulder position. Conversely to
      methylparathion and parathion, malathion did not promote phase separation. The
      overall data from fluorescence anisotropy and calorimetry indicate that the
      degree of effect of the insecticides on the physicochemical membrane properties
      correlates with toxicity to mammals. Therefore, the in vivo effects of
      organophosphorus compounds may be in part related with their ability to perturb
      the phospholipid bilayer structure, whose integrity is essential for normal cell
      function.

PMID- 11286980
TI  - Regulation of surfactant-like particle secretion by Caco-2 cells.
AB  - Surfactant-like particle (SLP) is a phosphatidylcholine (PC)-rich membrane
      produced in the small intestine, and its secretion is increased by fat feeding.
      In Caco-2 cells known to produce SLP, preincubation with [(3)H]palmitate labelled
      the SLP and was used as a marker for newly secreted membrane. SLP-associated PC
      and protein (d=1.07-1.08 g/ml in a linear non-equilibrium NaBr gradient) were
      secreted in parallel with triacylglycerols (TG) and at a rate about twice the
      control rate in response to feeding cells with an oleate/egg PC mixture.
      Cholesterol and apolipoprotein A-I identified only a small peak corresponding to
      high-density lipoprotein (HDL), but the largest peak corresponded with SLP
      (d=1.07-1.08). Palmitate incorporation into PC showed a similar small peak
      migrating at the density of HDL, but most labelled PC secreted from the cells was
      due to SLP. PC secretion, alkaline phosphatase activity, and newly synthesized
      immunoprecipitated SLP proteins from conditioned serum-free media migrated
      together at a density of >/=1.21 g/ml in a lipoprotein NaBr step gradient, and
      represented SLP. Glycerol incorporated into TG migrated at a peak density of 1.12
      g/ml, consistent with HDL secretion from cells incubated in serum-free media.
      These data confirm that the secreted PC in SLP is distinct from lipoprotein
      particles. Incorporation of [(3)H]palmitate into the PC fraction of either whole
      cell homogenate or isolated brush border membranes was not affected by oleate/egg
      PC feeding. Both Pluronic L-81, an inhibitor of chylomicron secretion, and BMS
      197636-02, a microsomal triglyceride transfer protein inhibitor, blocked the
      secretion of both TG and PC. Elevation of intracellular cAMP levels that
      stimulate surfactant secretion from type II pneumocytes caused a 50% reduction in
      SLP and TG secretion from Caco-2 cells. These results confirm the SLP response to
      fat feeding found in vivo, further supporting a role for SLP in TG secretion from
      the enterocyte, and show that the regulation of SLP secretion differs from that
      of pulmonary surfactant.

PMID- 11286981
TI  - Stretch-sensitive switching among different channel sublevels of an endothelial
      cation channel.
AB  - A mechanosensitive Ca(2+)-permeable cation channel was recorded by patch clamp in
      isolated rat aortic endothelial cells. A low level of channel activity could be
      observed after seal formation. The channel displayed some inward rectification
      and had a conductance for inward current of approx. 32 pS in Ca(2+)-free pipette
      and bath solutions. Negative suction of -10 to -20 mmHg increased the probability
      of the channel being open. When the negative pressure in the pipette was raised
      to -35 to -45 mmHg, the channel underwent an abrupt transition to a large
      conductance substate that was interrupted occasionally by two other low
      conductance levels. Under this condition, the overwhelming majority of openings
      and closings were between a main level of 83 pS and the closed level. Compared to
      the 32 pS substate, the 83 pS large conductance substate had shorter mean open
      and closed times. The two channel substates had similar ionic selectivity and
      both were sensitive to the inhibition of cGMP and protein kinase G. This is the
      first demonstration showing that mechanostress can change the single channel
      conductance level of an ion channel in eukaryotic cells.

PMID- 11286982
TI  - Nonlinear temperature modulation of sodium channel kinetics in GH(3) cells.
AB  - The effect of temperature on sodium channel function was examined in GH(3) cells,
      using the whole cell patch-clamp methodology. Specific parameters examined were
      current-voltage relationships, activation time, and inactivation time. For the
      temperature range studied, 23-37 degrees C, there was no change in the current
      voltage relationship. A linear response to temperature was seen in the
      inactivation time constant, tau(h). The activation time constant, tau(m), was
      clearly nonlinear, with a sharp discontinuity at 28 degrees C. This nonlinearity
      was especially evident at lower membrane voltages. These findings are consistent
      with the hypothesis that membrane structural changes, which occur during the
      thermotropic phase transition, are capable of influencing the function of the
      intramembranous portion of the channel. Caution should, therefore, be exercised
      in extrapolating data on channel function obtained at room temperature to
      physiological temperatures.

PMID- 11286983
TI  - p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific
      ligands, including monoclonal antibodies, to distal ends of PEG chains via p
      nitrophenylcarbonyl groups.
AB  - We have attempted to simplify the procedure for coupling various ligands to
      distal ends of liposome-grafted polyethylene glycol (PEG) chains and to make it
      applicable for single-step binding of a large variety of a primary amino group
      containing substances, including proteins and small molecules. With this in mind,
      we have introduced a new amphiphilic PEG derivative, p-nitrophenylcarbonyl-PEG
      1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (pNP-PEG-DOPE), synthesized by
      reaction of DOPE with excess of bis(p-nitrophenylcarbonyl)-PEG in a
      chloroform/triethylamine mixture. pNP-PEG-DOPE readily incorporates into
      liposomes via its PE residue, and easily binds primary amino group-containing
      ligands via its water-exposed pNP groups, forming stable and non-toxic urethane
      (carbamate) bonds. The reaction between the pNP group and the ligand amino group
      proceeds easily and quantitatively at pH around 8.0, and remaining free pNP
      groups are promptly eliminated by spontaneous hydrolysis. Therefore, pNP-PEG-DOPE
      could serve as a very convenient tool for protein attachment to the distal ends
      of liposome-grafted PEG chains. To investigate the applicability of the suggested
      protocol for the preparation of long-circulating targeted liposomes, we have
      coupled several proteins, such as concanavalin A (ConA), wheat germ agglutinin
      (WGA), avidin, monoclonal antimyosin antibody 2G4 (mon2G4), and monoclonal
      antinucleosome antibody 2C5 (mon2C5) to PEG-liposomes via terminal pNP groups and
      studied whether the specific activity of these immobilized proteins is preserved.
      The method permits the binding of several dozens protein molecules per single 200
      nm liposome. All bound proteins completely preserve their specific activity.
      Lectin-liposomes are agglutinated by the appropriate polyvalent substrates
      (mannan for ConA-liposomes and glycophorin for WGA-liposomes); avidin-liposomes
      specifically bind with biotin-agarose; antibody-liposomes demonstrate high
      specific binding to the substrate monolayer both in the direct binding assay and
      in ELISA. A comparison of the suggested method with the method of direct membrane
      incorporation was made. The effect of the concentration of liposome-grafted PEG
      on the preservation of specific protein activity in different coupling protocols
      was also investigated. It was also shown that pNP-PEG-DOPE-liposomes with and
      without attached ligands demonstrate increased stability in mouse serum.

PMID- 11286984
TI  - Role of the sugar moiety in the pharmacological activity of anthracyclines:
      development of a novel series of disaccharide analogs.
AB  - The sugar moiety is an essential component of anthracycline antibiotics for their
      topoisomerase poisoning activity and antitumor efficacy. Since the sugar
      interacts with the minor groove, modifications in this moiety could enhance the
      recognition potential of the drug at the target level. Based on this hypothesis,
      novel anthracyclines, disaccharides lacking the amino group in the first
      (aglycone-linked) sugar, were designed. The 3'-amino group in the first sugar was
      replaced by an hydroxyl group, and the second sugar residue was bound to the
      first sugar via an alpha (1-4) linkage. The cytotoxic and antitumor activities of
      disaccharide analogs of idarubicin were critically dependent on the optimal
      (axial) orientation of the second sugar residue. Although configurational
      requirements of the sugar moiety for optimal drug activity support a critical
      role of the external (non-intercalating) drug domains in the interaction of
      anthracyclines with the DNA-topoisomerase (ternary complex), the antitumor
      efficacy of disaccharide analogs is not fully explained by effects mediated by
      the nuclear enzyme target. The development of this novel disaccharide series may
      provide insights for a rational synthesis of anthracycline analogs with improved
      pharmacological profile.

PMID- 11286985
TI  - Broussochalcone A, a potent antioxidant and effective suppressor of inducible
      nitric oxide synthase in lipopolysaccharide-activated macrophages.
AB  - The antioxidant properties of broussochalcone A (BCA) and its effects on nitric
      oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages were
      investigated in this study. BCA, isolated from Broussonetia papyrifera Vent.,
      inhibited iron-induced lipid peroxidation in rat brain homogenate in a
      concentration-dependent manner with an IC(50) of 0.63 +/- 0.03 microM. It was as
      potent as butylated hydroxytoluene, a common antioxidant used for food
      preservation. In a diphenyl-2-picrylhydrazyl assay system, the radical-scavenging
      activity of BCA seemed to be more potent than that of alpha-tocopherol, its
      IC(0.200) being 7.6 +/- 0.8 microM. BCA could directly scavenge superoxide anion
      and hydroxyl radicals. These results indicated that BCA was a powerful
      antioxidant with versatile free radical-scavenging activity. On the other hand,
      we found that BCA suppressed NO production concentration-dependently, with an
      IC(50) of 11.3 microM in LPS-activated macrophages. This effect was not the
      consequence of a direct inhibitory action on the enzyme activity of inducible NO
      synthase (iNOS). Our results indicated that BCA exerts potent inhibitory effects
      on NO production, apparently mediated by its suppression of IkappaBalpha
      phosphorylation, IkappaBalpha degradation, nuclear factor-kappa B activation, and
      iNOS expression. Therefore, we conclude that the antioxidant activities of BCA
      and its inhibition of IkappaBalpha degradation and iNOS protein expression may
      have therapeutic potential, given that excessive free radicals and NO production
      have been associated with various inflammatory diseases.

PMID- 11286986
TI  - Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular
      endothelial growth factor in Hep3B cells.
AB  - YC-1 is a newly developed agent that inhibits platelet aggregation and vascular
      contraction. Although its effects are independent of nitric oxide (NO), it mimics
      some of the biological actions of NO. For example, it stimulates soluble
      guanylate cyclase (sGC) and increases intracellular cGMP concentration. Here, we
      tested the possibility that YC-1 inhibits hypoxia-inducible factor (HIF)-1
      mediated hypoxic responses, as does NO. Hep3B cells were used during the course
      of this work to observe hypoxic induction of erythropoietin (EPO) and vascular
      endothelial growth factor (VEGF), and the effects of YC-1 were compared with
      those of a NO donor, sodium nitropurruside (SNP). In hypoxic cells, YC-1 blocked
      the induction of EPO and VEGF mRNAs, and inhibited the DNA-binding activity of
      HIF-1. It suppressed the hypoxic accumulation of HIF-1alpha, but not its mRNA
      level. It also reduced HIF-1alpha accumulation induced by cobalt and
      desferrioxamine. Treatment with antioxidants did not recover the HIF-1alpha
      suppressed by YC-1. We examined whether these effects of YC-1 are related to the
      sGC/cGMP signal transduction system. Two sGC inhibitors examined failed to block
      the effects of YC-1, and 8-bromo-cGMP did not mimic actions of YC-1. The effects
      of YC-1 on the hypoxic responses were comparable with those of SNP. These results
      suggest that YC-1 and SNP suppressed the hypoxic responses by post
      translationally inhibiting HIF-1alpha accumulation. The YC-1 effect may be linked
      with the metal-related oxygen sensing pathway, and is not due to the stimulation
      of sGC. This observation implies that the inhibitory effects of YC-1 on hypoxic
      responses can be developed to suppress EPO-overproduction by tumor cells and
      tumor angiogenesis.

PMID- 11286987
TI  - Factors influencing the induction of DT-diaphorase activity by 1,2-dithiole-3
      thione in human tumor cell lines.
AB  - NAD(P)H:(quinone acceptor)oxidoreductase (DT-diaphorase) is a two-electron
      reducing enzyme that activates bioreductive antitumor agents and is induced by a
      wide variety of compounds including 1,2-dithiole-3-thione (D3T). We investigated
      factors influencing DT-diaphorase induction in fourteen human tumor cell lines.
      Four cell lines had basal DT-diaphorase activity that was increased by D3T
      treatment (group A), six cell lines had basal DT-diaphorase activity but the
      activity was not increased by D3T (group B), and four cell lines had low enzyme
      activity without, or with, D3T (group C). Two cell lines in group A and two cell
      lines in group B had a C to T polymorphism at base 609 in the NQO(1), DT
      diaphorase gene, in one allele, while all four cell lines in group C were
      homozygous mutants. The base 609 mutant NQO(1) gene produces a protein with
      little enzyme activity. In group A, D3T increased NQO(1) mRNA and wild-type
      protein, and also increased mutant protein in the two heterozygous cell lines. In
      group B, the inducer slightly increased NQO(1) mRNA, did not increase the wild
      type protein, but did increase the mutant protein in the two heterozygous cell
      lines. In group C, D3T increased NQO(1) mRNA as well as its mutant enzyme
      product. Transfection of the mutant NQO(1) gene into cells with two wild-type
      alleles did not alter DT-diaphorase activity. The results suggest that the lack
      of induction of DT-diaphorase activity is transcriptional in nature, that basal
      and induced expression of DT-diaphorase are regulated independently, and that
      mutant NQO(1) does not act as a dominant-negative to suppress DT-diaphorase
      activity.

PMID- 11286988
TI  - Stimulation of cyclooxygenase-2-activity by nitric oxide-derived species in rat
      chondrocyte: lack of contribution to loss of cartilage anabolism.
AB  - Cross-talk between inducible nitric oxide synthase (NOS II) and cyclooxygenase-2
      (COX-2) was investigated in rat chondrocytes. In monolayers, interleukin-1beta
      (IL-1beta) induced COX-2 and NOS II expression in a dose- and time-dependent
      manner, to produce high prostaglandin E(2) (PGE(2)) and nitrite (NO(2)(-)) levels
      in an apparently coordinated fashion. COX-2 mRNA was induced earlier (30 min.
      versus 4 hr) and less markedly (4-fold versus 12-fold at 24 hr) than NOS II, and
      was poorly affected by the translational inhibitor cycloheximide (CHX). IL-1beta
      did not stabilize COX-2 mRNA in contrast to CHX. Indomethacin and NS-398 lacked
      any effect on NO(2)(-) levels whereas L-NMMA and SMT reduced PGE(2) levels at
      concentration inhibiting NO(2)(-) production from 50 to 90%, even when added at a
      time allowing a complete expression of both enzymes (8 hr). Basal COX activity
      was unaffected by NO donors. The SOD mimetic, CuDips inhibited COX-2 activity by
      more than 75% whereas catalase did not. Inhibition of COX-2 by CuDips was not
      sensitive to catalase, consistent with a superoxide-mediated effect. In
      tridimensional culture, IL-1beta inhibited radiolabelled sodium sulphate
      incorporation while stimulating COX-2 and NOS II activities. Cartilage injury was
      corrected by L-NMMA or CuDips but not by NSAIDs, consistent with a peroxynitrite
      mediated effect. These results show that in chondrocytes: (i) COX2 and NOS II
      genes are induced sequentially and distinctly by IL-1beta; (ii) COX-1 and COX-2
      activity are affected differently by NO-derived species; (iii) peroxynitrite
      accounts likely for stimulation of COX-2 activity and inhibition of proteoglycan
      synthesis induced by IL-1beta.

PMID- 11286989
TI  - Effects of genistein on cell proliferation and cell cycle arrest in nonneoplastic
      human mammary epithelial cells: involvement of Cdc2, p21(waf/cip1), p27(kip1),
      and Cdc25C expression.
AB  - Genistein, a soy isoflavone, has been reported to inhibit the multiplication of
      numerous neoplastic cells, including those in the breast. However, there is
      limited information on the effect of genistein on nonneoplastic human breast
      cells. In the present studies, genistein inhibited proliferation of, and DNA
      synthesis in, the nonneoplastic human mammary epithelial cell line MCF-10F with
      an IC(50) of approximately 19-22 microM, and caused a reversible G2/M block in
      cell cycle progression. Genistein treatment (45 microM) increased the
      phosphorylation of Cdc2 by 3-fold, decreased the activity of Cdc2 by 70% after 8
      hr, and by 24 hr reduced the expression of Cdc2 by 70%. In addition, genistein
      enhanced the expression of the cell cycle inhibitor p21(waf/cip1) by 10- to 15
      fold, increased p21(waf/cip1) association with Cdc2 by 2-fold, and increased the
      expression of the tumor suppressor p53 by 2.8-fold. Genistein did not alter the
      expression of p27(kip1) significantly. Furthermore, genistein inhibited the
      expression of the cell cycle-associated phosphatase Cdc25C by 80%. From these
      results, we conclude that genistein inhibits the growth of nonneoplastic MCF-10F
      human breast cells by preventing the G2/M phase transition, induces the
      expression of the cell cycle inhibitor p21(waf/cip1) as well as its interaction
      with Cdc2, and inhibits the activity of Cdc2 in a phosphorylation-related manner.
      Down-regulation of the cell cycle-associated phosphatase Cdc25C combined with up
      regulation of p21(waf/cip1) expression appear to be important mechanisms by which
      genistein decreases Cdc2 kinase activity and causes G2 cell cycle arrest.

PMID- 11286990
TI  - Differential effect of simvastatin on various signal transduction intermediates
      in cultured human smooth muscle cells.
AB  - The underlying mechanism of the antiproliferative effect of S (simvastatin), a
      HMG-CoA reductase inhibitor, in vascular smooth muscle cells (SMC) is still
      poorly understood. In the present study, we used synchronized human SMC, isolated
      from left interior mammary artery, as an in vitro model to test the effects of S
      on platelet-derived growth factor (PDGF)-induced DNA synthesis, extracellular
      regulated kinase 1/2 (ERK1/2), p38/stress-activated protein kinase 2 (SAPK2),
      RhoA and Rac1 activation. ERK1/2 phosphorylation was triggered within 2 min of
      PDGF stimulation (early G1 phase) and was blocked by PD98059, a specific
      inhibitor of the ERK1/2 pathway, which also strongly inhibited PDGF-induced DNA
      synthesis (IC(50) = 10 micromol/L). PDGF quickly induced p38 phosphorylation
      (early G1 phase) and SB203580, a specific inhibitor of the p38/SAPK2 pathway,
      also blocked PDGF-induced DNA synthesis (IC(50) = 0.3 micromol/L). Translocation
      to the plasma membrane of small GTPases, such as RhoA and Rac1, could not be
      detected within 15 min of stimulation with PDGF or lysophosphatidic acid (LPA)
      (early G1 phase), but occurred after 24 hr of PDGF stimulation (late G1/S phase).
      S inhibited PDGF-induced DNA synthesis (IC(50) = 3.5 micromol/L), and this effect
      was dependent on intracellular mevalonate, farnesyl pyrophosphate, and
      geranylgeranyl pyrophosphate availability. The critical time period for the
      reversal of the S effect by mevalonate comprised both the early and late G1 phase
      of the SMC cycle. PDGF-induced ERK1/2 phosphorylation and PDGF-induced p38
      phosphorylation were not markedly affected by S during the whole G1 phase.
      However, S treatment blocked the PDGF- and LPA-induced membrane translocation of
      RhoA that occurred during the late G1/S phase. In the case of Rac1, the same
      process was also inhibited by S treatment. We concluded from these results that,
      in SMC, the early events associated with ERK1/2 and p38 signal transduction
      pathways, recruited for PDGF-mediated DNA synthesis, were insensitive to S
      action, whereas the mevalonate-dependent, posttranslational modification of RhoA
      and Rac1 molecules, required for PDGF-induced membrane translocation, was blocked
      by this drug. These results suggest that the antiproliferative effect of S can be
      explained not only by the blockage of RhoA-mediated signaling events but also by
      Rac1-mediated signaling events.

PMID- 11286991
TI  - Prooxidant activity of beta-hematin (synthetic malaria pigment) in arachidonic
      acid micelles and phospholipid large unilamellar vesicles.
AB  - Intraerythrocytic malaria parasite has evolved a unique pathway to detoxify
      hemoglobin-derived heme by forming a crystal of Ferri-protoporphyrin IX dimers,
      known as hemozoin or "malaria pigment." The prooxidant activity of beta-hematin
      (BH), the synthetic malaria pigment obtained from hematin at acidic pH, was
      studied in arachidonic acid micelles and phospholipid Large Unilamellar Vesicles
      (LUVs) and compared to that of alpha-hematin (AH, Ferri-protoporphyrin IX
      hydroxide) and hemin (HE, Ferri-protoporphyrin-chloride). Lipid peroxidation was
      measured as production of thiobarbituric acid reactive substances (TBARS). The
      extent of peroxidation induced by either AH or BH was strongly dependent upon the
      content of pre-existing hydroperoxides and efficiently inhibited by
      triphenylphosphine, a deoxygenating agent able to reduce hydroperoxides to
      hydroxides and by lipophilic scavengers. BH prooxidant activity was linearly
      related to the material, whereas that of AH seemed dependent on the aggregation
      state of the porphyrin. Maximal activity was observed when AH was present in
      concentration lower than 2 microM. In this case a shift of spectra in the Soret
      region, leading to the increase of the O.D. 400/385 nm ratio, suggested a
      transition toward a less aggregated state. BH prooxidant activity was
      significantly lower than that of monomeric AH, yet higher than that of AH
      aggregates. Differently from AH aggregates, BH-induced peroxidation was
      unaffected by GSH and inhibited rather than enhanced by acidic pH (5.7) and
      chloroquine. UV/Vis spectroscopy of AH aggregates at acidic pH, low GSH
      concentrations and chloroquine suggests a shift of AH aggregates toward the less
      aggregated state, more active as peroxidation catalyst.

PMID- 11286992
TI  - Inhibition of nicotinic acetylcholine receptors and calcium channels by clozapine
      in bovine adrenal chromaffin cells.
AB  - The effects of clozapine on the activities of nicotinic acetylcholine receptors
      (nAChRs) and voltage-sensitive calcium channels (VSCCs) were investigated and
      compared with those of chlorpromazine (CPZ) in bovine adrenal chromaffin cells.
      [(3)H]Norepinephrine ([(3)H]NE) secretion induced by activation of nAChRs was
      inhibited by clozapine and CPZ with half-maximal inhibitory concentrations
      (IC(50)) of 10.4 +/- 1.1 and 3.9 +/- 0.2 microM, respectively. Both cytosolic
      calcium increase and inward current in the absence of extracellular calcium
      induced by nicotinic stimulation were also inhibited by clozapine and CPZ, but
      the greater inhibition was achieved by CPZ. In addition, [(3)H]nicotine binding
      to chromaffin cells was inhibited by clozapine and CPZ with IC(50) values of
      approximately 19 and 2 microM, respectively. On the other hand, [(3)H]NE
      secretion induced by high K(+) was inhibited by clozapine and CPZ with similar
      IC(50) values of 15.5 +/- 3.8 and 17.1 +/- 3.9 microM, respectively. Our results
      suggest that clozapine, as well as CPZ, inhibits nAChRs and VSCCs, thereby
      causing inhibition of catecholamine secretion, and that clozapine is much less
      potent than CPZ in inhibiting nAChRs.

PMID- 11286994
TI  - Inhibition of Kv1.3 channels by H-89 (N--[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulfonamide) independent of protein kinase A.
AB  - The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A
      (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary
      (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89
      decreased Kv1.3 currents and accelerated the decay rate of current inactivation
      in a concentration-dependent manner with an IC(50) value of 1.70 microM. These
      effects were completely reversible after washout. Intracellular infusion with PKA
      inhibitors, adenosine 3', 5'-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein
      kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not
      prevent the inhibitory action of H-89 on the current. H-89 applied to the
      cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches.
      These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.

PMID- 11286993
TI  - Specific involvement of G(alphai2) with epidermal growth factor receptor
      signaling in rat hepatocytes, and the inhibitory effect of chronic ethanol.
AB  - We have previously shown that chronic alcohol consumption inhibits liver
      regeneration by impairing epidermal growth factor receptor (EGFR)-operated
      phospholipase C-(gamma1) (PLC-(gamma1)) activation and the resultant rise in
      intracellular [Ca(2+)](i). In hepatocytes, activation of PLC-(gamma1) by EGFR
      requires involvement of a pertussis toxin-sensitive inhibitory guanine nucleotide
      binding regulatory protein (G(alphai)) as an intermediate. In the present study,
      we first identified the G(alphai) protein isoform associated with the activated
      EGFR, and then examined whether the toxic effect of alcohol on EGFR signaling and
      liver cell proliferation was exerted on this association. In cultured hepatocytes
      from control rats, EGF rapidly induced association between EGFR and G(alphai2)
      but not other G(alphai) isoforms. In hepatocytes from rats fed alcohol for 16
      weeks, EGF failed to stimulate this association of G(alphai2) with the EGFR. The
      impairment of EGFR-G(alphai2) complex formation caused by alcohol was associated
      with a decreased level of G(alphai2) in the plasma membrane fraction
      (approximately 50% control). Pertussis toxin, an inhibitor of G(alphai) function,
      produced an analogous disruption of the association between G(alphai2) and the
      EGFR, as well as inhibiting EGF-induced DNA synthesis. It is concluded that, in
      hepatocytes, G(alphai2) is specific among G(alphai) isoforms in coupling
      activation of the EGFR to other signaling pathways that control cell
      proliferation. Impaired coupling of G(alphai2) of EGFR could contribute to the
      mechanism by which chronic alcohol exposure inhibits liver regeneration.

PMID- 11286995
TI  - Involvement of oxygen radicals in cytarabine-induced apoptosis in human
      polymorphonuclear cells.
AB  - We investigated apoptosis in polymorphonuclear neutrophils (PMNs) induced by
      cytarabine (Ara-C). This drug increased apoptosis by 100% with respect to the
      controls after 3 hr of incubation. This increase was inhibited by N-acetyl-L
      cysteine (NAC) or diphenyleneiodonium chloride (DPI). Ara-C alone caused an early
      increase (after a 30-min incubation) in intracellular oxidant generation
      (inhibitable by rotenone, fumonisin b1, and DPI) and in protein tyrosine
      phosphorylations (inhibitable by NAC). The drug also affected the observed
      reduction of dimethylthiazol diphenyltetrazolium bromide (MTT). No extracellular
      release of reactive oxygen species (ROS) was elicited by the addition of Ara-C,
      while the drug increased the release of ROS by N-formyl-leucyl-phenylalanine-(f
      MLP) but not phorbol 12-myristate 13-acetate-stimulated PMNs. This phenomenon was
      abolished by the addition of genistein, whereas such an effect was not observed
      following the addition of 1-(5-isoquinolynilsulfonyl)-2-methylpiperazine (H7).
      Ara-C induced ROS release from PMNs in the presence of subthreshold
      concentrations of f-MLP (priming effect). These results indicate that
      intracellular ROS production from mitochondria promotes Ara-C-induced apoptosis.
      Ara-C primes plasma membranes by a mechanism involving protein tyrosine
      phosphorylations and may also contribute to ROS generation from the granules.

PMID- 11286996
TI  - Role of petasin in the potential anti-inflammatory activity of a plant extract of
      petasites hybridus.
AB  - A large production of leukotrienes (LTs) can be induced in human eosinophils or
      neutrophils by priming with granulocyte-macrophage colony-stimulating factor and
      subsequent stimulation with platelet-activating factor (PAF) or the anaphylatoxin
      C5a. Here, we investigated the effects of a plant extract of petasites hybridus
      (Ze339) and its isolated active sesquiterpene ester petasin in these two in vitro
      cell models. Zileuton, a 5-lipoxygenase inhibitor, was used as a positive
      control. All compounds inhibited both cysteinyl-LT synthesis in eosinophils and
      LTB(4) synthesis in neutrophils. In contrast, only Ze339 and petasin, but not
      zileuton, abrogated PAF- and C5a-induced increases in intracellular calcium
      concentrations. These data suggest that Ze339 and petasin may block, compared to
      zileuton, earlier signalling events initiated by G protein-coupled receptors in
      granulocytes, perhaps at the level of or proximal to phospholipase C(beta). Taken
      together, petasin appears to be one major active compound of petasites hybridus
      extract, since it demonstrates the same inhibitory activities on calcium fluxes
      and subsequent LT generation in both eosinophils and neutrophils as Ze339 does.

PMID- 11286997
TI  - Nuclear and mitochondrial apoptotic pathways of p53.
AB  - In contrast to p53-mediated cell cycle arrest, the mechanisms of p53-mediated
      apoptosis in response to cellular stresses such as DNA damage, hypoxia and
      oncogenic signals still remain poorly understood. Elucidating these pathways is
      all the more pressing since there is good evidence that the activation of
      apoptosis rather than cell cycle arrest is crucial in p53 tumor suppression.
      Moreover, the therapeutic interest in p53 as the molecular target of anticancer
      intervention rests mainly on its powerful apoptotic capability. This puzzling
      elusiveness suggests that p53 not only engages a plethora of downstream pathways
      but itself might possess a biochemical flexibility that goes beyond its role as a
      mere transcription factor. Recent evidence of a direct pro-apoptotic role of p53
      protein at mitochondria suggests a synergistic effect with its transcriptional
      activation function and brings an unexpected new level of complexity into p53
      apoptotic pathways.

PMID- 11286998
TI  - The solution structure of the disulphide-linked homodimer of the human trefoil
      protein TFF1.
AB  - The trefoil factor family protein, TFF1, forms a homodimer, via a disulphide
      linkage, that has greater activity in wound healing assays than the monomer.
      Having previously determined a high-resolution solution structure of a monomeric
      analogue of TFF1, we now investigate the structure of the homodimer formed by the
      native sequence. The two putative receptor/ligand recognition domains are found
      to be well separated, at opposite ends of a flexible linker. This contrasts
      sharply with the known fixed and compact arrangement of the two trefoil domains
      of the closely related TFF2, and has significant implications for the mechanism
      of action and functional specificity of the TFF of proteins.

PMID- 11286999
TI  - Down-regulation of peroxisome proliferator-activated receptor-gamma gene
      expression by sphingomyelins.
AB  - We recently demonstrated that the sphingomyelin (SM) content of adipocyte
      membranes was negatively correlated with the expression of peroxisome
      proliferator-activated receptor-gamma (PPARgamma) in the subcutaneous adipose
      tissue of obese women with variable degrees of insulin resistance. We have now
      investigated whether SM really does have an impact on the expression of PPARgamma
      in 3T3-F442A adipocytes. Adding SM to the culture medium for 24 h caused a
      significant increase in SM content of adipocyte membranes and an acyl chain
      length-dependent decrease in the levels of PPARgamma mRNA and protein. The longer
      the acyl chain of the fatty acid of SM, the greater was the decrease in
      PPARgamma. These data suggest that the nature of the fatty acid is important in
      the regulation of PPARgamma by the SM pathway.

PMID- 11287000
TI  - Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting
      subunit and inhibits myosin phosphatase activity.
AB  - Myotonic dystrophy protein kinase (DMPK) and Rho-kinase are related. An important
      function of Rho-kinase is to phosphorylate the myosin-binding subunit of myosin
      phosphatase (MYPT1) and inhibit phosphatase activity. Experiments were carried
      out to determine if DMPK could function similarly. MYPT1 was phosphorylated by
      DMPK. The phosphorylation site(s) was in the C-terminal part of the molecule.
      DMPK was not inhibited by the Rho-kinase inhibitors, Y-27632 and HA-1077. Several
      approaches were taken to determine that a major site of phosphorylation was T654.
      Phosphorylation at T654 inhibited phosphatase activity. Thus both DMPK and Rho
      kinase may regulate myosin II phosphorylation.

PMID- 11287001
TI  - Depletion of phosphatidylethanolamine affects secretion of Escherichia coli
      alkaline phosphatase and its transcriptional expression.
AB  - In this report we demonstrate that depletion of the major phospholipid
      phosphatidylethanolamine, a single non-bilayer forming phospholipid of
      Escherichia coli, significantly reduces the secretion efficiency of alkaline
      phosphatase in vivo. Secretion, however, is correlated with the content in
      membranes of cardiolipin, which in combination with selected divalent cations has
      a strong tendency to adopt a non-bilayer state indicating the possible
      involvement of lipid polymorphism in efficient protein secretion. Depletion of
      this zwitterionic phospholipid also inhibits expression of the protein controlled
      by the endogenous P(PHO) promoter but not the P(BAD) promoter, which is suggested
      to be due to the effect of unbalanced phospholipid composition on the
      orthophosphate signal transduction system (Pho regulon) through an effect on its
      membrane bound sensor.

PMID- 11287002
TI  - Dual Ser and Thr phosphorylation of CPI-17, an inhibitor of myosin phosphatase,
      by MYPT-associated kinase.
AB  - Phosphorylation of CPI-17 and PHI-1 by the MYPT1-associated kinase (M110 kinase)
      was investigated. M110 kinase is a recently identified serine/threonine kinase
      with a catalytic domain that is homologous to that of ZIP kinase (ZIPK. GST-rN
      ZIPK, a constitutively active GST fusion fragment, phosphorylates CPI-17 (but not
      PHI-1) to a stoichiometry of 1.7 mol/mol. Phosphoamino acid analysis revealed
      phosphorylation of both Ser and Thr residues. Phosphorylation sites in CPI-17
      were identified as Thr 38 and Ser 12 using Edman sequencing with (32)P release
      and a point mutant of Thr 38.

PMID- 11287003
TI  - A deteriorated triple-helical scaffold accelerates formation of the Tetrahymena
      ribozyme active structure.
AB  - The Tetrahymena group I ribozyme requires a hierarchical folding process to form
      its correct three-dimensional structure. Ribozyme activity depends on the
      catalytic core consisting of two domains, P4-P6 and P3-P7, connected by a triple
      helical scaffold. The folding proceeds in the following order: (i) fast folding
      of the P4-P6 domain, (ii) slow folding of the P3-P7 domain, and (iii) structure
      rearrangement to form the active ribozyme structure. The third step is believed
      to directly determine the conformation of the active catalytic domain, but as yet
      the precise mechanisms remain to be elucidated. To investigate the folding
      kinetics of this step, we analyzed mutant ribozymes having base substitution(s)
      in the triple-helical scaffold and found that disruption of the scaffold at A105G
      results in modest slowing of the P3-P7 folding (1.9-fold) and acceleration of
      step (iii) by 5.9-fold. These results suggest that disruption or destabilization
      of the scaffold is a normal component in the formation process of the active
      structure of the wild type ribozyme.

PMID- 11287004
TI  - Functional coupling with Galpha(q) and Galpha(i1) protein subunits promotes high
      affinity agonist binding to the neurotensin receptor NTS-1 expressed in
      Escherichia coli.
AB  - To analyze the coupling of Galpha subunits to the rat neurotensin receptor NTS-1
      (NTR), fusion proteins were expressed in Escherichia coli with various Galpha
      subunits covalently linked to the receptor C-terminus. The presence of Galpha(q)
      or Galpha(i/q), in which the six C-terminal residues of Galpha(i1) were replaced
      with those from Galpha(q), increased the percentage of receptors in the agonist
      high-affinity state. This effect was less pronounced for wild-type Galpha(i1) and
      not observed for Galpha(i/s). Functional coupling of neurotensin receptor to
      Galpha was demonstrated by neurotensin-induced [(35)S]GTPgammaS binding for the
      Galpha(q), Galpha(i/q) and Galpha(i1) subunits, but not for Galpha(i/s). Our
      results extend previous findings of the dual coupling of NTR to pertussis toxin
      sensitive and -insensitive G-proteins in Chinese hamster ovary cells with
      preference for the latter.

PMID- 11287005
TI  - The BPS domain of Grb10 inhibits the catalytic activity of the insulin and IGF1
      receptors.
AB  - Grb7, Grb10 and Grb14 comprise a family of adaptor proteins that interact with
      numerous receptor tyrosine kinases upon receptor activation. Between the
      pleckstrin homology (PH) domain and the Src homology 2 (SH2) domain of these
      proteins is a region of approximately 50 residues known as the BPS (between PH
      and SH2) domain. Here we show, using purified recombinant proteins, that the BPS
      domain of Grb10 directly inhibits substrate phosphorylation by the activated
      tyrosine kinase domains of the insulin receptor and the insulin-like growth
      factor 1 (IGF1) receptor. Although inhibition by the BPS domain is dependent on
      tyrosine phosphorylation of the kinase activation loop, peptide competition
      experiments indicate that the BPS domain does not bind directly to
      phosphotyrosine. These studies provide a molecular mechanism by which Grb10
      functions as a negative regulator of insulin- and/or IGF1-mediated signaling.

PMID- 11287006
TI  - UV-light-dependent binding of a visual arrestin 1 isoform to photoreceptor
      membranes in a neuropteran (Ascalaphus) compound eye.
AB  - Arrestins are regulators of the active state of G-protein-coupled receptors.
      Towards elucidating the function of different arrestin subfamilies in sensory
      cells, we have isolated a novel arrestin 1, Am Arr1, from the UV photoreceptors
      of the neuropteran Ascalaphus macaronius. Am Arr1 forms a phylogenetic clade with
      antennal and visual Arr1 isoforms of invertebrates. Am Arr1 undergoes a light
      dependent binding cycle to photoreceptor membranes, as reported earlier only for
      members of the arrestin 2 subfamily. This suggests a common control mechanism for
      the active state of invertebrate rhodopsins and G-protein-coupled receptors of
      antennal sensory cells. Furthermore, it implies that a strict correlation of
      distinct arrestin isoforms to distinct functions is not a general principle for
      invertebrate sensory cells.

PMID- 11287007
TI  - The Rev/Rex homolog HERV-K cORF multimerizes via a C-terminal domain.
AB  - Expression of human endogenous retrovirus K (HERV-K) is associated with germ-cell
      neoplasia. HERV-K encodes a protein of the Rev/Rex family, cORF, that supports
      cellular transformation and binds the promyelocytic leukemia zinc finger (PLZF)
      protein implicated in spermatogenesis. Rev/Rex function invariably depends on
      multimerization. Here we show that cORF likewise self-associates to form higher
      order oligomers. Amino acids (aa) 47-87 in cORF are sufficient, aa 75-87
      essential for self-association. Consistently, this domain is predicted to form a
      hydrophobic alpha-helix that may represent an oligomerization interface. The
      existence of a dimerization-competent cORF mutant lacking PLZF-binding activity
      (cORF47-87) suggests a way of dominant negative inhibition of the proposed tumor
      susceptibility factor cORF.

PMID- 11287008
TI  - Annexin A5 D226K structure and dynamics: identification of a molecular switch for
      the large-scale conformational change of domain III.
AB  - The domain III of annexin 5 undergoes a Ca(2+)- and a pH-dependent conformational
      transition of large amplitude. Modeling of the transition pathway by computer
      simulations suggested that the interactions between D226 and T229 in the IIID
      IIIE loop on the one hand and the H-bond interactions between W187 and T224 on
      the other hand, are important in this process [Sopkova et al. (2000) Biochemistry
      39, 14065-14074]. In agreement with the modeling, we demonstrate in this work
      that the D226K mutation behaves as a molecular switch of the pH- and Ca(2+)
      mediated conformational transition. In contrast, the hydrogen bonds between W187
      and T224 seem marginal.

PMID- 11287009
TI  - A sequence motif responsible for ER export and surface expression of Kir2.0
      inward rectifier K(+) channels.
AB  - Integral membrane proteins are sorted via the secretory pathway. It was proposed
      that this pathway is non-selective provided that the cargo protein is properly
      assembled and lacks an endoplasmic reticulum (ER) retention signal. However,
      recent experimental evidence suggests that efficient export of proteins from the
      ER to the Golgi complex is not simply a default pathway. Here we demonstrate a
      novel sequence motif (FxYENEV) in the cytoplasmic C-terminus of mammalian inward
      rectifier potassium (Kir) channels which determines ER export. This motif is
      found to be both necessary and sufficient for efficient export from the ER that
      eventually leads to efficient surface expression of Kir2.1 channels.

PMID- 11287010
TI  - NaCl-activated nucleoside diphosphate kinase from extremely halophilic archaeon,
      Halobacterium salinarum, maintains native conformation without salt.
AB  - Enzymes from extremely halophilic archaea are readily denatured in the absence of
      a high salt concentration. However, we have observed here that a nucleoside
      diphosphate kinase prepared from Halobacterium salinarum was active and stable in
      the absence of salt, though it has the amino acid composition characteristic of
      halophilic enzymes. Recombinant nucleoside diphosphate kinase expressed in
      Escherichia coli requires salt for activation in vitro, but once it acquires the
      proper folding, it no longer requires the presence of salts for its activity and
      stability.

PMID- 11287011
TI  - Directed evolution of beta-galactosidase from Escherichia coli by mutator strains
      defective in the 3'-->5' exonuclease activity of DNA polymerase III.
AB  - Directed evolution of Escherichia coli beta-galactosidase into variants featuring
      beta-glucosidase activity was challenged. To this end, mutagenesis of lacZ was
      performed by replication in E. coli CC954, a mutator strain containing a DNA
      polymerase III defective in 3'-->5' exonuclease activity. beta-Galactosidase
      variants can be isolated upon mutagenesis of lacZ hosted into the self
      transmissible episome F'128. Optimal evolution of lacZ can be achieved by
      propagation of E. coli CC954/F'128 cultures for 15 generations; further growth of
      mutator cultures for 37 or 55 generations imposes a high mutational load on lacZ
      and hinders the selection of efficiently evolved clones.

PMID- 11287012
TI  - Fertility options for female cancer patients: facts and fiction.
AB  - OBJECTIVE: To review the latest progress in the prevention of ovarian failure
      induced by chemo/radiotherapy, as well as the latest advances in culture
      technology and transplantation of frozen-thawed ovarian tissue. DESIGN: The
      English-language literature was searched with PubMed and related references.
      CONCLUSION(S): The development of combination chemotherapy and radiotherapy has
      improved the long-term survival of young cancer patients who are then frequently
      faced with iatrogenic ovarian failure and its consequences. The use of prior and
      concomitant GnRH analogs with chemotherapy offers encouraging results in animal
      studies with regard to prevention of ovarian failure. Adequately controlled
      research projects are needed to define the utility of GnRHa cotreatment in women
      cancer patients exposed to prolonged chemotherapy. Ovarian tissue
      cryopreservation is the optimal procedure for follicle banking. Theoretic options
      include returning the banked tissue back to the original pedicle so that
      pregnancy could be achieved naturally. Alternatively, the tissue can be grafted
      to a heterotopic site, either as an autograft (i.e., rectus abdominis muscle
      sheath) or as a xenograft (i.e., immunodeficient mice). Follicles could also be
      grown in vitro. Until reliable ovarian culture technology becomes available,
      autologous transplantation offers the best prospect of using frozen-thawed
      ovarian tissue. A primary concern, however, is the issue of microscopic
      metastatic disease to the ovary and the possibility of tumor reimplantation.
      Areas of research should focus on optimizing the freeze/thaw procedure for
      ovarian tissue, minimizing the ischemia-reperfusion injury after transplantation,
      and detecting minimal residual disease in ovarian tissue grafts.

PMID- 11287014
TI  - A comparison of intrauterine versus intracervical insemination in fertile single
      women.
AB  - OBJECTIVE: To compare the efficacy of intrauterine insemination (IUI) and
      intracervical insemination (ICI) when used by fertile single women in a donor
      insemination program. DESIGN: Prospective randomized crossover study. SETTING:
      Donor insemination program (not an infertility clinic). PATIENT(S): Single
      fertile women choosing to inseminate with frozen donor semen. INTERVENTION(S):
      Clients received procreative counseling and screening and were then randomly
      assigned to begin office insemination with ICI or IUI. If additional insemination
      cycles were required, the clients used the method opposite their previous method
      of insemination until pregnancy was achieved. MAIN OUTCOME MEASURE(S): Monthly
      fecundity rate was compared between the two methods of insemination. RESULT(S):
      Sixty-two women contributed a total of 189 cycles, 94 by IUI and 95 by ICI. The
      monthly fecundity rate for IUI was 15%, as compared with 9% for ICI, (P=0.14).
      When the analysis was confined to cycles in which only one insemination was
      performed (64 IUI and 65 ICI cycles), the monthly fecundity rates were 14% for
      IUI and 5% for ICI (P=0.04). CONCLUSION(S): Intrauterine insemination with frozen
      donor sperm is more effective than intracervical insemination for single women
      without known fertility problems.

PMID- 11287015
TI  - Effect of the total motile sperm count on the efficacy and cost-effectiveness of
      intrauterine insemination and in vitro fertilization.
AB  - OBJECTIVE: To determine prognostic factors for achieving a pregnancy with
      intrauterine insemination (IUI) and IVF. To compare the effectiveness and cost
      effectiveness of IUI and IVF based on semen analysis results. DESIGN:
      Retrospective cohort study. SETTING: Academic university hospital-based
      infertility center. PATIENT(S): One thousand thirty-nine infertile couples
      undergoing 3,479 IUI cycles. Four hundred twenty-four infertile couples
      undergoing 551 IVF cycles. INTERVENTION(S): IUI and IVF treatment. MAIN OUTCOME
      MEASURE(S): Multiple logistic regression analysis was used to assess the
      significance of prognostic factors including a woman's age, gravidity, duration
      of infertility, diagnoses, use of ovulation induction, and sperm parameters for
      predicting the outcomes of clinical pregnancy and live birth rate after the first
      cycle of IUI and IVF. The relative effectiveness and cost-effectiveness of these
      treatments were then determined based on sperm count results. RESULT(S): Female
      age, gravidity, and use of ovulation induction were all independent factors in
      predicting pregnancy after IUI. The average total motile sperm count in the
      ejaculate was also an important factor, with a threshold value of 10 million. For
      IVF, only female age was an important predictor for both clinical and ongoing
      pregnancy. When the average total motile sperm count was under 10 million, IVF
      with ICSI was more cost-effective than IUI in our clinic. CONCLUSION(S): An
      average total motile sperm count of 10 million may be a useful threshold value
      for decisions about treating a couple with IUI or IVF.

PMID- 11287016
TI  - Cyclin-dependent kinase 5 is expressed in both Sertoli cells and metaphase
      spermatocytes.
AB  - OBJECTIVE: To gain insight into the function of cyclin-dependent kinase 5 (Cdk5)
      in spermatogenesis. DESIGN: The expression of the Cdk5 protein was determined
      with the use of immunohistochemical and immunoblot analysis. SETTING: Academic
      research laboratory. ANIMAL(S): Adult mouse and archival human testicular tissue
      were used for the immunohistochemical analysis. Adult mice were used as the
      source of tissues for the immunoblot analysis. INTERVENTION(S): The
      immunohistochemical analysis was performed with an anti-Cdk5 antibody. The double
      immunohistochemical analysis was performed with anti-Cdk5 and alpha-tubulin
      antibodies. Immunoblotting was used to examine multiple mouse tissues for Cdk5
      expression. MAIN OUTCOME MEASURE(S): Analysis of Cdk5 protein distribution.
      RESULT(S): Cdk5 was localized specifically within the cytoplasm of Sertoli cells
      and meiotic metaphase germ cells. The double immunohistochemistry analysis
      demonstrated the co-localization of Cdk5 and alpha-tubulin within the Sertoli
      cells. Western blot analysis revealed a high level of expression of Cdk5 in the
      testicular lysate. CONCLUSION(S): The cyclin-dependent kinases are known
      regulators of the cell cycle; however, Cdk5 expression previously has been
      described in terminally differentiated cells of the brain. The present evidence
      of an association between Cdk5 and microfilaments of Sertoli cells and meiotic
      metaphase germ cells suggests a role of Cdk5 in both seminiferous tubule function
      and meiosis.

PMID- 11287017
TI  - Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA
      fragmentation, in fertile and infertile men.
AB  - OBJECTIVE: To evaluate two different assays of human sperm DNA integrity, DNA
      denaturation (DD) and DNA fragmentation (DF), and to correlate these with
      standard semen parameters. DESIGN: Prospective, observational study. SETTING:
      University infertility clinic. PATIENT(S): Forty consecutive semen samples from
      33 nonazoospermic men presenting for infertility evaluation and 7 fertile men
      presenting for vasectomy. INTERVENTION(S): Assessment of sperm concentration,
      motility, morphology, DD and DF. MAIN OUTCOME MEASURE(S): Sperm DD and DF in
      fertile and infertile men. RESULT(S): The mean (+/-SE) rates of DD and DF were
      significantly higher in infertile subjects compared to fertile controls,
      respectively: 25.4 +/- 3.0 vs. 10.2 +/- 2.3 (P=.028) and 27.6 +/- 2.5 vs. 13.3 +/
      2.5% (P=.016). DF and DD correlated strongly (r = 0.71, P<.0001). Also, DD and
      DF correlated negatively with standard semen parameters (concentration, motility,
      and morphology), the strongest correlation being with sperm motility.
      CONCLUSION(S): The strong correlation between sperm DD and DF, and the higher
      levels of sperm DNA damage in infertile compared with fertile men, indicate that
      male infertility is associated with poor sperm DNA integrity. Although infertile
      men may father children with assisted conception, fertilization with DNA-damaged
      spermatozoa may increase the risk of genetic disease in the offspring.

PMID- 11287018
TI  - Karyotype of the abortus in recurrent miscarriage.
AB  - OBJECTIVE: To assess the chromosomal aberrations in the abortus in recurrent
      miscarriage and the live birth rate after a euploid or aneuploid miscarriage.
      DESIGN: Retrospective analysis. SETTING: Tertiary referral unit in university
      hospital. PATIENT(S): One hundred sixty-seven patients with 3 to 16 miscarriages
      before 20 weeks. INTERVENTION(S): Material collected at curettage from 167
      abortuses was analyzed by standard G-banding techniques. MAIN OUTCOME MEASURE(S):
      The incidence of aberrations and the outcome of the subsequent pregnancy were
      assessed according to the embryonic karyotype. RESULT(S): In this study 125
      specimens were successfully karyotyped. Of these, 29% (36 of 125) had chromosome
      aberrations; 94% of the aberrations were aneuploidy, and 6% were structural. The
      most prevalent anomalies were chromosome 16, 18, and 21 trisomies, triploidy, and
      monosomy X. After an aneuploid miscarriage, there was a 68% subsequent live birth
      rate (13 of 19) compared to the 41% (16 of 39) rate after a euploid abortion.
      CONCLUSION(S): The low (29%) incidence of aberrations indicates that alternative
      mechanisms may be responsible for the majority of recurrent miscarriages. These
      figures provide a basis for assessing the efficacy of therapy for recurrent
      miscarriage. If further studies confirm that patients with karyotypically
      abnormal fetuses have a good prognosis, an informed decision can be made as to
      whether further investigations and treatment should be undertaken.

PMID- 11287019
TI  - Interleukin 1 receptor antagonist polymorphism in women with idiopathic recurrent
      miscarriage.
AB  - OBJECTIVE: Proinflammatory cytokines have been described as etiologic factors in
      idiopathic recurrent miscarriage. We investigated the relation between idiopathic
      recurrent miscarriage and polymorphisms in the gene encoding for the interleukin
      1 receptor antagonist, an indigenous modulator of proinflammatory immune
      response. DESIGN: Prospective case control study. SETTING: Academic research
      institution. PATIENT(S): One hundred five women with a history of three or more
      consecutive pregnancy losses before 20 weeks of gestation and 91 healthy,
      postmenopausal controls with at least two live births and no history of pregnancy
      loss. INTERVENTION(S): Peripheral venous puncture. MAIN OUTCOME MEASURE(S):
      Polymerase chain reaction was performed to identify the different alleles of the
      gene encoding for interleukin 1 receptor antagonist. RESULT(S): Allele
      frequencies among women with idiopathic recurrent miscarriage and controls were
      0.34 and 0.11, respectively, for the polymorphic allele 2 (P=.002; odds ratio:
      7.4, confidence interval: 2.9--10.8) and.05 and.05, respectively, for the
      polymorphic allele 3 (P=.6; odds ratio: 1.3, confidence interval: 0.8--2.3).
      Allele 2 was present in homozygous form in 9% of women with idiopathic recurrent
      miscarriage. In contrast, 1% of the control women were homozygous for this allele
      (P<.001; odds ratio: 13.5, confidence interval: 7.5--21.8). CONCLUSION(S): These
      data support a role for allele 2 of the gene encoding for interleukin 1 receptor
      antagonist as genetic determinant of idiopathic recurrent miscarriage.

PMID- 11287020
TI  - Dynamics of the development of multiple follicles during ovarian stimulation for
      in vitro fertilization using recombinant follicle-stimulating hormone (Puregon)
      and various doses of the gonadotropin-releasing hormone antagonist ganirelix
      (Orgalutran/Antagon).
AB  - OBJECTIVE: To investigate relations between dose of GnRH antagonist and
      follicular phase characteristics. DESIGN: Randomized controlled multicenter
      trial. SETTING: Tertiary referral fertility centers. PATIENT(S): Three hundred
      and twenty-nine IVF patients. INTERVENTION(S): Ovarian stimulation for IVF with
      recombinant FSH starting on cycle day 2. From cycle day 7 onwards, cotreatment
      was provided with 0.0625, 0.125, 0.25, 0.5, 1.0, or 2.0 mg/d GnRH antagonist.
      MAIN OUTCOME MEASURE(S): Number of follicles, total follicular surface area,
      gonadotropin, and serum steroid concentrations. RESULT(S): In 311 patients,
      similar follicular growth was observed in all treatment groups. FSH levels
      increased during the follicular phase. Late follicular phase LH, androstenedione
      (AD), and E(2) levels showed a GnRH antagonist dose-related decrease (P<0.05).
      Late follicular phase E(2) levels correlated with total follicular surface area,
      AD, LH, and FSH (all P<0.001). Increasing GnRH antagonist doses exhibited
      additional suppressive action on E(2) levels. CONCLUSION(S): Follicular growth
      was unaffected by the dose of GnRH antagonist. A rise in follicular phase FSH
      serum concentrations during the follicular phase, largely related to exogenous
      FSH, enabled ongoing follicular growth in all treatment groups. The effect of
      GnRH antagonist on late follicular phase E(2) levels could not be exclusively
      attributed to suppression of LH.

PMID- 11287021
TI  - Serum and follicular fluid hormone levels during in vitro fertilization after
      short- or long-course treatment with a gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: To examine the impact of flare (short) vs. down-regulation (long) GnRH
      agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen
      concentrations in women undergoing IVF treatment cycles. DESIGN: Prospective
      observational study. SETTING: IVF clinic. PATIENT(S): One hundred sixteen
      ovulatory subjects undergoing IVF. INTERVENTION(S): Fifty-eight ovulatory
      patients undergoing a down-regulation regimen matched with 58 undergoing the
      flare regimen as part of an IVF cycle. MAIN OUTCOME MEASURE(S): Serum
      concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and E(2) on
      the day of hCG administration were compared between the two groups. In addition,
      the FF P4, 17OHP4, A, T, and E(2) levels were compared in the two groups.
      RESULT(S): Serum LH was significantly higher with the flare regimen (15.2 +/-
      1.14 IU/L, P<.05) when compared with results with the down-regulation protocol
      (9.5 +/- 0.77 IU/L). In addition, FF A was significantly higher in the flare
      protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the down-regulation
      protocol (27 +/- 2.44 ng/mL). Serum and FF P4, 17OH P4, T, and E(2) were not
      statistically significantly different between the two groups. CONCLUSION(S):
      Serum LH and FF A are significantly higher in the flare regimen in comparison
      with the down-regulation regimen. Circulating LH appears to play a role in
      determining FF A concentration.

PMID- 11287022
TI  - Serum human chorionic gonadotropin levels are correlated with body mass index
      rather than route of administration in women undergoing in vitro fertilization-
      embryo transfer using human menopausal gonadotropin and intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To compare subcutaneous (SC) and intramuscular (IM) hCG administration
      and their association with body mass index (BMI) in women undergoing IVF-ET using
      hMG and ICSI. DESIGN: Prospective, randomized controlled trial. SETTING: Private
      infertility clinic. PATIENT(S): Twenty-one ovulatory women, 29-39 years, were
      enrolled. Treatment of one patient who failed to respond to hMG was canceled.
      INTERVENTION(S): A standard IVF-ET treatment plan using an initial dose of 300 U
      of hMG was followed. Patients were randomly assigned to receive 10,000 IU hCG,
      either IM in the gluteal region or SC in the lower abdomen. Exactly 12 hours
      later, serum for hCG determination was obtained. All oocytes were fertilized
      using ICSI technology. MAIN OUTCOME MEASURE(S): Human chorionic gonadotropin
      levels 12 hours after injection, BMI, and oocyte maturity. RESULT(S): No
      significant differences in hCG levels were found, with mean levels of 225 +/- 24
      mIU/mL for SC injection versus 213 +/- 26 mIU/mL for IM injection. No differences
      were observed in the percentage of mature oocytes. A significant negative
      correlation was found between BMI and hCG levels in all patients, regardless of
      route of administration. CONCLUSION(S): The highest levels of hCG were measured
      in women with the lowest BMI. Patients' body size, rather than route of hCG
      delivery, appears to determine circulating levels of hCG.

PMID- 11287023
TI  - In vitro fertilization for cancer patients and survivors.
AB  - OBJECTIVE: To determine in vitro fertilization (IVF) outcome in cancer patients.
      DESIGN: Retrospective record review. SETTING: Academic, hospital-based assisted
      reproductive technology (ART) program. PATIENT(S): Sixty-nine women undergoing
      113 IVF/gamete intrafallopian transfer (GIFT) cycles after cancer treatment in
      one partner, and 13 women undergoing 13 IVF cycles for embryo cryopreservation
      before chemotherapy/radiation. INTERVENTION(S): IVF, intracytoplasmic sperm
      injection (ICSI), assisted hatching, and gamete intrafallopian transfer as
      indicated. MAIN OUTCOME MEASURE(S): Delivery rate, spontaneous abortion rate,
      number of embryos cryopreserved, cancer diagnosis, systemic or local cancer
      treatment, female age, amount of gonadotropin used, treatment duration, peak
      estradiol level, and number of oocytes and embryos. RESULT(S): The women
      undergoing IVF after chemotherapy had poorer responses to gonadotropins than did
      the women with locally treated cancers even though they were younger (33.5 +/-
      1.3 vs. 36.5 +/- 0.5 years; P<.05). The delivery rates after the women had
      undergone chemotherapy tended to be lower among the systemic treatment group than
      it was for the local cancer treatment group: (13.3% [2 of 15] vs. 40% [14 of 56,
      P=NS]). The women who had cryopreserved all embryos before chemotherapy produced
      more oocytes (18.7 +/- 3.2 vs. 14.5 +/- 1.2) and embryos (11.3 +/- 1.9 vs. 7.5 +/
      0.7) than did the women who had had a history of local cancer treatment. Male
      factor infertility as a result of cancer treatment is well treated with IVF or
      intracytoplasmic sperm injection, where indicated (32% delivery rate/cycle), with
      no difference between the frozen sperm banked before cancer treatment and fresh
      sperm produced after treatment. CONCLUSION(S): Chemotherapy diminishes the
      response to ovulation induction in assisted reproductive technologies. IVF with
      cryopreservation of embryos allows embryo banking before chemotherapy for women
      who have been newly diagnosed with cancer. Factors related to the partner affect
      the success of IVF for male factor infertility as a result of cancer treatment.

PMID- 11287024
TI  - Paracervical block with and without conscious sedation: a comparison of the pain
      levels during egg collection and the postoperative side effects.
AB  - OBJECTIVE: To compare the pain levels during egg collection and the subsequent
      postoperative side effects in patients receiving a paracervical block (PCB) with
      and without conscious sedation. DESIGN: A prospective, randomized, double-blind,
      and placebo-controlled study. SETTING: A tertiary assisted reproduction unit.
      PATIENT(S): 150 patients undergoing egg collection. INTERVENTION(S): Randomized
      to receive PCB only (control group) and PCB in conjunction with conscious
      sedation (sedation group). MAIN OUTCOME MEASURE(S): Vaginal and abdominal pain
      levels; severity of postoperative side effects. RESULT(S): The median pain levels
      during vaginal punctures were 12.0 (2.5th--97.5th centiles: 0--84.3) and 30.0
      (2.5th--97.5th centiles: 0--100) in the sedation and placebo groups,
      respectively. The corresponding median abdominal pain levels were 16.5 (2.5th-
      97.5th centiles: 0--100) and 43.0 (2.5th--97.5th centiles: 0--100). The pain
      levels were significantly higher in the placebo group than the sedation group.
      There were no significant differences between the two groups in the severity of
      nausea, vomiting, dizziness, and drowsiness. CONCLUSION(S): Patients who received
      only a PCB during the egg collection experienced 2.5 times higher levels of
      vaginal and abdominal pain as compared to those who received both PCB and
      conscious sedation. The use of PCB along is not recommended for all patients but
      it may be considered with selected patients after they have been given extensive
      counseling.

PMID- 11287025
TI  - Symptomatic treatment of premenstrual mastalgia in premenopausal women with
      lisuride maleate: a double-blind placebo-controlled randomized study.
AB  - OBJECTIVE: To determine the therapeutic effect of lisuride maleate on
      premenstrual mastalgia in premenopausal women. DESIGN: Double-blind randomized
      prospective study. SETTING: Department of obstetrics and gynecology at a
      university hospital. PATIENT(S): Sixty women with premenstrual mastalgia were
      included in the study. Study and control groups consisted of 30 women each.
      INTERVENTION(S): Women enrolled in the study and control group were given one
      tablet daily (0.2 mg) of lisuride maleate or placebo orally for 2 months.
      Severity of mastalgia was evaluated using the visual analog scale. MAIN OUTCOME
      MEASURE(S): Severity of mastalgia and side effects of the drug administered.
      RESULT(S): Mastalgia subsided significantly in women receiving lisuride maleate
      compared with controls. There were no significant side effects from lisuride
      maleate. Prolactin levels decreased significantly in the group receiving
      lisuride, which correlated well with pain resolution. CONCLUSION(S): Lisuride
      maleate may be useful for the symptomatic treatment of premenstrual mastalgia.

PMID- 11287026
TI  - Candidate gene analysis in premature pubarche and adolescent hyperandrogenism.
AB  - OBJECTIVE: To identify genetic markers associated with premature pubarche in
      children and hyperandrogenism in adolescent girls. DESIGN: Association study.
      SETTING: Academic research environment. PATIENT(S): Forty children with premature
      pubarche (PP), 29 adolescent girls with hyperandrogenism (HA), and 15 healthy
      control women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genetic variations
      at five loci selected because of known associations with hyperandrogenism,
      insulin resistance, hyperinsulinemia, or obesity. RESULT(S): Heterozygosity for
      CYP21 mutations was identified in 14 of 40 (35%) PP, 8 of 29 (28%) HA, and 1 of
      30 (3%) controls. Heterozygosity for HSD3B2 variants was identified in 3 of 40
      (7.5%) PP, 5 of 29 (17%) HA, and 0/15 controls. Among the PP, 11 of 80 (14%), 5
      of 80 (6%), and 7 of 80 (9%) alleles showed the IRS-1, GRL, and ADRB3 variants,
      respectively. Among the HA, 5 of 58 (8.6%), 3 of 58 (5%), and 6 of 58 (10%)
      alleles showed the IRS-1, GRL, and ADRB3 variants, respectively. Among the
      control participants, variant allele frequency was 1 of 30 (3.3%) for IRS-1, 2 of
      30 (6.6%) for GRL, and 2 of 30 (6.6%) for ADRB3. CONCLUSION(S): Our findings
      suggest that the development of PP and HA can be associated with the occurrence
      of multiple sequence variants at five susceptibility loci, especially
      steroidogenic enzyme genes. This approach offers a novel paradigm to investigate
      and identify the genetic factors relevant to polycystic ovary syndrome.

PMID- 11287027
TI  - Natural versus induced twinning and pregnancy outcome: a Dutch nationwide survey
      of primiparous dizygotic twin deliveries.
AB  - OBJECTIVE: To compare obstetrical outcome of twin pregnancies after assisted
      reproduction with that of natural twin pregnancies. DESIGN: Retrospective
      national database study. SETTING: Academic Medical Centre. PATIENT(S): One
      thousand ninety-three primiparous mothers registered in the Dutch National Birth
      Registry who gave birth to a dizygotic (DZ) twin (male/female) in 1994, 1995, and
      1996. We compared 613 natural twin pregnancies and 480 twin pregnancies born
      after assisted reproduction. MAIN OUTCOME MEASURE(S): Gestational length, mode of
      delivery, mode of presentation of the children, birth weight, APGAR score,
      congenital anomalies, perinatal mortality rate, highest recorded maternal
      diastolic blood pressure, and maternal postpartum complications. RESULT(S): Rates
      of perinatal mortality and very premature parturition (<29 weeks) were lower in
      natural twin mothers. Overall, induced DZ twins were born 3.5 days earlier with a
      lower birth weight and APGAR score compared with controls. Rates of congenital
      anomalies and incidence of cesarean section were not different. The highest
      recorded diastolic blood pressure was lower in induced twinning with a 30% lower
      incidence of diastolic blood pressure >90 mm Hg. CONCLUSION(S): Obstetric outcome
      for induced DZ twin pregnancy is less optimal than in natural DZ twin pregnancy.
      Twinning in assisted reproduction is known for its contribution to the high rate
      of premature deliveries, but in addition being a subfertile patient undergoing
      treatment makes an intrinsic contribution to adverse events as well.

PMID- 11287028
TI  - Short-term effects of three continuous hormone replacement therapy regimens on
      platelet tritiated imipramine binding and mood scores: a prospective randomized
      trial.
AB  - OBJECTIVE: To evaluate the effects of continuous hormone replacement therapy
      (HRT) regimens on platelet-tritiated ((3)H-) imipramine binding (Bmax) and mood.
      DESIGN: Prospective randomized study. SETTING: University hospital. PATIENT(S):
      Sixty postmenopausal patients. INTERVENTION(S): Randomization to 3 months of
      daily treatment with tibolone and conjugated equine estrogen (CEE).625 mg
      combined either with 2.5 or 5 mg of medroxyprogesterone acetate (MPA). The
      inclusion criteria-matched patients declined for HRT were prescribed daily
      alendronate. Pre- and posttreatment blood sampling for Bmax and mood evaluation
      with the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory
      (STAI) were done. MAIN OUTCOME MEASURE(S): Pre- and posttreatment Bmax and mood
      scores. RESULT(S): As compared with baseline, both CEE+MPA regimens and tibolone
      significantly increased Bmax. The comparisons of percent change from baseline
      Bmax for the CEE+MPA and tibolone groups were similar. All three HRT regimens
      improved the BDI significantly, while there were no significant changes in the
      STAI. In the alendronate group, there were no significant changes in both pre-
      and posttreatment Bmax and mood scores. CONCLUSION(S): Continuous treatment with
      CEE+MPA and tibolone increases platelet (3)H-imipramine binding and improves
      mood. Mood-enhancing effects of tibolone may occur through the serotonergic
      system, as is the case with estrogen.

PMID- 11287029
TI  - Delayed first injection of the once-a-month injectable contraceptive containing
      25 mg of medroxyprogesterone acetate and 5 mg of E(2)-cypionate: effects on
      ovarian function.
AB  - OBJECTIVE: To assess whether women who were administered the first injection of
      DMPA+E(2)C on day 7 of their menstrual cycle (delayed injection) exhibit the same
      degree of ovarian suppression as women who receive it on day 5 of their menstrual
      cycle. DESIGN: Multicenter, randomized controlled trial. SETTING: Reproductive
      health clinics. PATIENT(S): Women aged between 18 and 38 years (inclusive)
      willing to use DMPA+E(2)C as their method of contraception. INTERVENTION(S):
      Participants received a DMPA+E(2)C injection on day 5 (control group, n = 41) or
      day 7 (delayed-injection group, n = 117) of their menstrual cycle. MAIN OUTCOME
      MEASURE(S): Ovarian activity and follicular development determined by serial
      serum progesterone levels and vaginal ultrasound. RESULT(S): Participants who
      received DMPA+E(2)C on day 5 of their menstrual cycle (control group) exhibited
      no more than limited follicular growth (no follicle >16 mm). Of those women who
      received DMPA+E(2)C on day 7 of their menstrual cycle (delayed-injection group),
      21 (18%) showed some follicular growth, of whom 4 (3%) ovulated. CONCLUSION(S):
      The first injection of DMPA+E(2)C given on day 7 of a menstrual cycle does not
      provide the same inhibition of ovarian activity as that observed when it is
      administered on day 5 of the menstrual cycle.

PMID- 11287030
TI  - A one-year experience with a capitated health care plan for infertility.
AB  - OBJECTIVE: To report on a one-year experience participating in a capitated
      healthcare plan for infertility. DESIGN: Prospective study. SETTING: University
      population. PATIENT(S): Reproductive-age women 15 to 50 years. INTERVENTION(S):
      The first-generation Lewin infertility algorithm and CATHI software were used to
      negotiate infertility services under a capitated arrangement for $0.50 per member
      per month. The following reports our experience for the fiscal year 1997. MAIN
      OUTCOME MEASURE(S): Infertility services rendered, pregnancy rate, cost of
      services, collection rates. RESULT(S): Five thousand forty-six women representing
      39,689 member months generated 39 new and 198 return visits. Thirty-two percent
      of the patients required three visits or less; six patients generated 22% of the
      visits. Fifty-one percent listed infertility as one of their chief complaints;
      31% had mixed diagnoses. Eight (7.6%) patients required surgery, 11 (10.5%)
      patients underwent either IVF or GIFT cycles. Total charges submitted were
      $176,636; the amount assigned to specialty care was $135,277, and to IVF/GIFT,
      $33,433. Total capitated payments, including copayments, was $126,256 under the
      reproductive medicine agreement and $32,891 under the infertility rider. This
      resulted in a 71% gross collections rate. CONCLUSION(S): This study indicates
      that entering into a capitated health care plan to provide an infertility benefit
      can produce a successful result.

PMID- 11287031
TI  - Follicular viability and morphology of sheep ovaries after exposure to
      cryoprotectant and cryopreservation with different freezing protocols.
AB  - OBJECTIVE: To test the toxicity of cryoprotectant in sheep ovarian tissue and to
      determine optimal conditions for freezing hemiovary cortex. DESIGN: Small
      follicles (<60 microm in diameter) were isolated enzymatically for viability
      testing. Dead and live follicles were identified by using trypan blue staining,
      and follicle morphology was examined histologically. SETTING: Centre hospitalo
      universitaire de Biologie de la Reproduction, Hopital Edouard Herriot, Lyon,
      France. ANIMAL(S): Lambs 5 to 6 months of age. INTERVENTION(S): Two-millimeter
      slices of hemiovarian cortex were prepared for cryoprotectant toxicity tests and
      freezing procedures. MAIN OUTCOME MEASURE(S): Follicular mortality and histologic
      structure. RESULT(S): For freezing procedures, the concentration of
      cryoprotectant was increased to 2 M on the basis of results of cryoprotectant
      toxicity tests in fresh tissues. Follicular mortality rates were 4.6% with of 2 M
      dimethyl sulfoxide (DMSO) and 3.8% with 2 M of propylene glycol (PROH). After
      freezing with semiautomatic seeding, follicular mortality rates were 8.4% (2 M of
      DMSO) and 12.4% (2 M of PROH). Tissue morphology was well preserved with 1.5 M of
      DMSO or PROH. With 1.5 M DMSO, results of the slow cooling protocol (2 degrees
      C/min) without seeding and the standard very slow cooling protocol (0.3 degrees
      C/min) were similar. CONCLUSION(S): Optimal survival of primordial follicles in
      the sheep was obtained by using a slow cooling protocol with semiautomatic
      seeding at 2 M of DMSO.

PMID- 11287032
TI  - Molecular characterization of fibroblasts isolated from human peritoneum and
      adhesions.
AB  - OBJECTIVE: To determine the response of adhesion and peritoneal fibroblasts to
      hypoxia. DESIGN: Prospective experimental study. SETTING: University medical
      center. PATIENT(S): Primary cultures of fibroblasts established from the
      peritoneal and adhesion tissues of the same patients (n = 2) to minimize genetic
      variations. INTERVENTION(S): Hypoxia treatment of the primary cultured
      fibroblast. MAIN OUTCOME MEASURE(S): Analyze the expression of extracellular
      matrix (ECM) components, metalloproteinases and their tissue inhibitors, growth
      factors, and cytokines in adhesion and peritoneal fibroblasts under normal and
      hypoxic conditions by reverse transcriptase/polymerase chain reaction analysis.
      RESULT(S): Compared to peritoneal fibroblasts, adhesion fibroblasts had a
      significant increase in the basal mRNA levels for collagen I, fibronectin, MMP-1,
      TIMP-1, TGF-beta 1, TGF-beta 2, and IL-10. Hypoxia resulted in a further increase
      in collagen 1, fibronectin, TIMP-1, TGF-beta 1, TGF-beta 2, IL-10, and IFN-gamma
      mRNA levels in both peritoneal and adhesion fibroblasts. The increase was more
      profound in adhesion fibroblasts. CONCLUSION(S): Hypoxia induces molecular
      changes in both peritoneal and adhesion fibroblasts, creating a milieu that
      favors adhesion development. The effect of hypoxia was more profound on adhesion
      fibroblasts.

PMID- 11287033
TI  - Effects of chilling to 0 degrees C on the morphology of meiotic spindles in human
      metaphase II oocytes.
AB  - OBJECTIVE: To determine the effects of chilling to 0 degrees C on the meiotic
      spindle of human metaphase II oocytes, as observed by optical sectioning
      microscopy. DESIGN: Laboratory study. SETTING: Academic research laboratory in a
      medical school. PATIENT(S): Seventy-two women undergoing infertility treatment
      donated a total of 108 oocytes. INTERVENTION(S): Metaphase II oocytes were
      stripped of their cumulus cells, cooled directly to 0 degrees C, and held for
      periods of 1 to 10 minutes. They were then fixed at 37 degrees C, stained for
      immunofluorescence, and examined microscopically. MAIN OUTCOME MEASURE(S):
      Morphology of the meiotic spindle in chilled and control oocytes. RESULT(S):
      Microscopic evaluations of 46 chilled oocytes revealed various time-dependent
      changes in microtubules compared to 9 control oocytes. After 1 minute at 0
      degrees C, spindle damage was negligible, but in oocytes cooled for 2 or 3
      minutes, there was obvious shortening of the spindle and loss of polarity.
      Cooling to 0 degrees C for 4 to 9 minutes resulted in increasingly more drastic
      changes; by 10 minutes the spindles had totally disappeared. Despite
      depolymerization of microtubular tubulin at 0 degrees C, the chromosomes did not
      become dispersed, but remained anchored even in the absence of spindles.
      CONCLUSION(S): Even brief exposure of human oocytes to temperatures near 0
      degrees C causes profound alterations of the meiotic spindle.

PMID- 11287034
TI  - Aspirin dose dependently inhibits the interleukin-1 beta-stimulated increase in
      inducible nitric oxide synthase, nitric oxide, and prostaglandin E(2) production
      in rat ovarian dispersates cultured in vitro.
AB  - OBJECTIVE: Determine if aspirin inhibits the IL-1 beta-stimulated expression of
      inducible nitric oxide synthase (iNOS), nitric oxide (NO), and prostaglandin E(2)
      (PGE(2)) in rat ovarian dispersates cultured in vitro. DESIGN: Prospective,
      controlled in vitro study. SETTING: Academic research laboratory. ANIMALS:
      Ovaries collected from immature rats. INTERVENTION(S): Ovaries were collected
      from immature rats and enzymatically dispersed. Ovarian dispersates were placed
      into plates containing media alone or media supplemented with IL-1 beta (100
      U/mL) and varying concentrations of aspirin (0, 1, 3, 5 and 10 mM). Ovarian
      dispersates were cultured in a humidified environment of 5% CO(2) in air at 37
      degrees C for 24 or 48 hours. MAIN OUTCOME MEASURE(S): Twenty-four- and 48-hour
      iNOS, nitrite (a stable metabolite of NO), and PGE(2) levels were determined from
      ovarian dispersates cultured in vitro. RESULT(S): Administration of IL-1 beta
      increased nitrite and PGE(2) levels over that observed in the control group after
      culture of ovarian dispersates for 24 and 48 hours. Aspirin dose dependently
      reduced the IL-1 beta-stimulated increase in nitrite production from ovarian
      dispersates after culture for 24 and 48 hours. Aspirin completely (24 hours) or
      dose dependently (48 hours) prevented the IL-beta-stimulated increase in PGE(2.)
      Coadministration of IL-1 beta and aspirin (10 mM) attenuates IL-1 beta-stimulated
      iNOS expression after culture for 24 and 48 hours. CONCLUSION(S): Aspirin
      significantly inhibits the IL-1 beta-stimulated expression of iNOS, NO, and
      PGE(2) in ovarian dispersates cultured in vitro.

PMID- 11287035
TI  - Xanthine oxidase in eutopic and ectopic endometrium in endometriosis and
      adenomyosis.
AB  - OBJECTIVE: To investigate the expression of xanthine oxidase in eutopic and
      ectopic endometrium in endometriosis and adenomyosis. DESIGN: Immunohistochemical
      identification of xanthine oxidase in endometrial tissues by using polyclonal
      antibody. SETTING: University hospital. PATIENT(S): Thirty-four women with
      endometriosis, 34 women with adenomyosis, and 44 fertile control women.
      INTERVENTION(S): Biopsy samples were obtained from the endometrium throughout the
      menstrual cycle. MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining
      (evaluation nomogram) score of endometrial cells. RESULT(S): The level of
      xanthine oxidase expression in the glandular epithelium of control varied
      according to menstrual phase, but no such variation in expression was seen in
      endometriosis. Variation in xanthine oxidase expression was observed during the
      menstrual cycle in patients with adenomyosis; this variation differed completely
      from that in controls. Xanthine oxidase expression was found in ectopic
      endometrial tissue in all cases. The mean evaluation nomogram levels in the
      glandular epithelium in adenomyosis tissue were as high as those in the early
      secretory phase in the eutopic endometrium. CONCLUSION(S): Aberrant expression of
      xanthine oxidase in eutopic and ectopic endometrium appears to play a pathologic
      role in endometriosis and adenomyosis.

PMID- 11287036
TI  - Differential expression of integrin alpha v and beta 3 in serosal tissue of human
      intraperitoneal organs and adhesion.
AB  - OBJECTIVE: To assess the expression of integrin alpha v and beta 3 in the serosal
      tissue of intraperitoneal organs and adhesions in persons with and without
      adhesions. DESIGN: Prospective study. SETTING: Academic research centers.
      PATIENT(S): Fifty-seven patients undergoing abdominal or pelvic surgery. MAIN
      OUTCOME MEASURE(S): Integrin alpha v and beta 3 messenger RNA (mRNA) expression
      was evaluated by quantitative reverse transcription polymerase chain reaction.
      RESULT(S): The serosal tissue of the parietal peritoneum, uterus, fallopian
      tubes, ovary, and the large and small bowel, as well as peritoneal adhesions,
      skin, fascia, subcutaneous tissue, and omentum, expresses integrin alpha v and
      beta 3 mRNA. The level of alpha v and beta 3 mRNA expression varied among these
      tissues; expression of the former substance was highest in uterine serosa and
      lowest in the skin and small bowel, and expression of the latter substance was
      highest in the fallopian tubes and skin and lowest in the uterine serosa.
      Parietal peritoneum and adhesions express equal levels of integrin alpha v;
      however, integrin beta 3 expression was >100-fold lower in adhesions than in
      peritoneum. The level of integrin beta 3 expression in omentum, small and large
      bowels, and subcutaneous tissue was 100-fold to 10,000-fold lower than in other
      tissues. CONCLUSION(S): Serosal tissue of peritoneal organs and adhesions express
      variable levels of integrin alpha v and beta 3 mRNA. On the basis of such
      variation and the knowledge that tissue injury alters local integrin expression,
      integrins may play a key role in adhesion development, particularly in tissue
      with higher integrin expression.

PMID- 11287037
TI  - Role of the pentanucleotide (tttta)(n) polymorphism in the promoter of the CYP11a
      gene in the pathogenesis of hirsutism.
AB  - OBJECTIVE: To determine if the (tttta)(n) repeat polymorphism in the promoter
      region of CYP11a gene is associated with hirsutism and hyperandrogenism in women
      from Spain. DESIGN: Controlled clinical study. SETTING: Tertiary-care
      institutional hospital. PATIENT(S): Ninety-two hirsute women and 33 healthy
      control women. INTERVENTION(S): Basal and adrenocorticotropin-stimulated serum
      samples and genomic DNA extracted and purified from whole-blood samples were
      obtained during the follicular phase of the menstrual cycle. MAIN OUTCOME
      MEASURE(S): CYP11a (tttta)(n) repeat-polymorphism genotype and serum ovarian and
      adrenal androgen levels. RESULT(S): None of the CYP11a (tttta)(n) polymorphic
      alleles was associated with hirsutism. The absence of the four-repeat-units
      allele (4R-- genotype), which has been reported by other authors to be associated
      with polycystic ovary syndrome (PCOS), was found in 22.4% of the women studied
      here and was equally distributed among patients and controls, independently of
      the presence of PCOS and/or ovarian or adrenal hyperandrogenism. No differences
      were observed in serum hormone concentrations in 4R-- individuals as compared
      with subjects with at least one four-repeat-units allele. CONCLUSION(S): The
      (tttta)(n) repeat polymorphism in the promoter region of CYP11a does not appear
      to play any significant role in the pathogenesis of hirsutism and
      hyperandrogenism in women from Spain.

PMID- 11287038
TI  - Diagnostic inadequacy of dilatation and curettage.
AB  - OBJECTIVE: To assess the diagnostic inadequacy of dilatation and curettage (D&C)
      by comparing histologic findings with this technique with those obtained after
      hysterectomy. DESIGN: Retrospective clinical study. SETTING: University
      affiliated hospital. PATIENT(S): Three hundred ninety-seven patients with
      abnormal uterine bleeding who underwent D&C and, within 2 months, hysterectomy
      because of histologic findings or persistence of symptoms. MAIN OUTCOME
      MEASURE(S): Comparison of histologic findings on D&C with those obtained after
      hysterectomy. RESULT(S): In 248 of 397 patients (62.5%), D&C failed to detect
      intrauterine disorders subsequently found at hysterectomy; the sensitivity was
      46%, the specificity was 100.0%, the positive predictive value was 100.0%, and
      the negative predictive value was 7.1%. CONCLUSION(S): Dilatation and curettage
      is an inadequate diagnostic and therapeutic tool for all uterine disorders; this
      technique missed 62.5% of major intrauterine disorders, and all endometrial
      disorders were still present in the removed uterus.

PMID- 11287039
TI  - Gross and histologic characteristics of laparoscopic injuries with four different
      energy sources.
AB  - OBJECTIVE: To compare the gross and histologic effects of bipolar and monopolar
      cautery, ultrasonic scalpel, and CO(2) laser on porcine ureter, bladder, and
      rectum. DESIGN: Experimental prospective study. SETTING: Cleveland Clinic
      Foundation Animal Research Laboratory, Cleveland, Ohio. ANIMAL(S): Nonpregnant
      adult female pigs. INTERVENTION(S): The rectum, bladder, and ureters of 12 female
      pigs were injured with four different laparoscopic energy sources. MAIN OUTCOME
      MEASURE(S): Gross measurements of injured tissue and histologic analysis of the
      depth of the tissue injury. RESULT(S): Gross assessment results were that
      monopolar injuries of the bowel and bladder were significantly longer than
      ultrasonic injuries (P<0.01). Injuries were generally manifest as coagulative
      denaturation of collagen bundles. This resulted in an eosinophilic homogenization
      of tissue. Nuclei were retained in the injured tissue, although in most cases
      they had a pyknotic, streamed appearance. The CO(2) laser caused no deep-tissue
      injury. CONCLUSION(S): Laparoscopic energy sources injure tissue differently.
      Monopolar cautery appears to have the most lateral spread of thermal energy. The
      CO(2) laser appears to cause the least deep-tissue injury.

PMID- 11287040
TI  - Electroejaculation before chemotherapy in adolescents and young men with cancer.
AB  - OBJECTIVE: To evaluate the outcome of repeated electroejaculation for obtaining
      semen from adolescents and young men before initiation of anticancer therapies.
      DESIGN: Retrospective clinical study. SETTING: Bikur Cholim Hospital, Jerusalem,
      Israel. PATIENT(S): Six young male patients (average age, 18+/-3 years) with
      diagnosed cancer who underwent 12 procedures of electroejaculation before
      chemotherapy. INTERVENTION(S): Transrectal electroejaculation. Semen was
      cryopreserved in small aliquots. MAIN OUTCOME MEASURE(S): Semen analysis.
      RESULT(S): In all patients, semen was obtained by electroejaculation. Sperm count
      and motility were relatively low; mean values were 16 x 10(6) (range, 0--45 x
      10(6)) and 14% (range, 0--53%) respectively. CONCLUSION(S): If necessary,
      electroejaculation can be performed in adolescents, and sperm may be obtained by
      repeated treatments over a short period.

PMID- 11287041
TI  - Histocompatibility leukocyte antigen-G is not expressed by endometriosis or
      endometrial tissue.
AB  - OBJECTIVE: The immunological mechanisms that support persistence and
      proliferation of ectopic endometrial implants within the peritoneal cavity of
      women with endometriosis are unknown. Inhibition of natural killer (NK) and
      cytotoxic T-cell function has been proposed as a mechanism. We tested the
      hypothesis that expression of a nonclassical major histocompatibility antigen,
      HLA-G, might explain the local immunosuppression associated with ectopic
      endometrium. DESIGN: Nested case-control study of women with and without
      laparoscopic evidence of endometriosis. SETTING: Reproductive endocrinology
      clinic at a university hospital. PATIENT(S): Peritoneal fluid specimens from 10
      women with revised AFS stage I-IV endometriosis and from 10 age-matched normal
      controls without laparoscopic evidence of endometriosis were tested for the
      presence of HLA-G protein. Endometriosis and normal endometrial biopsies from
      four patients were used to prepare stromal cell cultures directly evaluated for
      HLA-G protein. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The expression of
      HLA-G in peritoneal fluid, tissue, and cell cultures was determined by
      immunoblotting with a specific monoclonal antibody. RESULT(S): HLA-G protein was
      not detectable in peritoneal fluid specimens of endometriosis patients or
      controls. Moreover, ectopic and normal endometrial tissues and stromal cells did
      not express HLA-G. CONCLUSION(S): Immune cell inhibition in endometriosis must be
      mediated by factors other than HLA-G.

PMID- 11287042
TI  - Uterine fistula induced by hysteroscopic resection of an embolized migrated
      fibroid: a rare complication after embolization of uterine fibroids.
AB  - OBJECTIVE: To describe a case in which hysteroscopic removal of a fibroid that
      had migrated through the uterine wall induced formation of a uterine fistula.
      DESIGN: After embolization of uterine fibroids, an investigative clinical,
      sonographic, and hysteroscopic protocol was followed. SETTING: Gynecologic clinic
      of a university hospital. PATIENT(S): A 38-year-old woman undergoing embolization
      of uterine arteries for uterine fibroids. INTERVENTION(S): Angiography-guided
      transcatheter bilateral embolization of uterine arteries, with clinical,
      sonographic, and hysteroscopic follow-up. MAIN OUTCOME MEASURE(S): Patient
      morbidity and satisfactory intercourse. RESULT(S): Six months after embolization
      of the uterine arteries, the patient presented migration of the fibroid through
      the uterine wall. Hysteroscopic removal of the fibroid induced posthysteroscopic
      formation of a uterine fistula. CONCLUSION(S): After embolization of the uterine
      arteries, thorough follow-up examination of the uterine cavity is strictly
      recommended. Diagnosis of a uterine wall perforation can identify an abnormal
      source of uterine bleeding, and patients should be counseled to avoid pregnancy
      until the lesion heals completely.

PMID- 11287043
TI  - Serum leptin concentrations are higher in azoospermic than in normozoospermic
      men.

PMID- 11287045
TI  - Local injection of hyperosmolar glucose solution versus salpingotomy for tube
      preserving therapy in women with unruptured tubal pregnancy and a serum hCG level
      of <2,500 IU/L.

PMID- 11287044
TI  - Vitamin supplementation and pregnancy outcome in women with recurrent early
      pregnancy loss and hyperhomocysteinemia.

PMID- 11287046
TI  - Sex chromosome aneuploidy in sperm cells obtained from Hodgkin's lymphoma
      patients before therapy.

PMID- 11287047
TI  - Nonsurgical female sterilization: comparison of intrauterine application of
      quinacrine alone or in combination with ibuprofen.

PMID- 11287048
TI  - High implantation and pregnancy rates with transfer of human hatching day 6
      blastocysts.

PMID- 11287050
TI  - Decreased corticotropin-releasing hormone (CRH) concentrations in the
      cerebrospinal fluid of eucortisolemic suicide attempters.
AB  - Several lines of evidence suggest a dysregulation of the adrenocortical (HPA)
      system with hypersecretion of CRH is associated with suicidal behavior. However,
      controversial results have emerged from the determination of corticotropin
      releasing hormone (CRH) concentrations in the lumbar cerebrospinal fluid (CSF) of
      suicide attempters probably due to methodological differences. We simultaneously
      measured CRH concentrations in the CSF and in the plasma of 41 psychiatric in
      patients with different diagnoses (affective disorder, schizophrenia, personality
      disorders, adjustment disorder, substance abuse) and eight neurological control
      subjects. We also measured plasma cortisol concentrations because data from
      animal experiments suggest that cortisol may influence CSF CRH concentrations.
      The major finding was that patients who attempted suicide prior to admission had
      significantly lower CSF CRH concentrations than psychiatric patients without
      suicidal behavior. CRH concentrations were significantly higher in the CSF than
      in plasma in both, psychiatric patients and neurological control subjects. There
      was no significant difference between suicide attempters and patients with acute
      suicidal ideations. The latter group showed a trend towards lower CSF CRH
      concentrations compared with the neurological control subjects. Patients with
      affective disorder alone as well as patients with multiple diagnoses, but not
      schizophrenic patients, showed significantly lower CSF CRH concentrations than
      neurological control subjects. Plasma CRH and plasma cortisol concentrations did
      not differ among diagnostic groups or between suicide attempters vs. non
      attempters. Further studies with more homogeneous samples, drug-free patients and
      with simultaneous assessment of various parameters of the HPA system are
      warranted.

PMID- 11287051
TI  - Increased serum S100B protein in schizophrenia: a study in medication-free
      patients.
AB  - S100B protein, a calcium binding protein produced and released by glial cells,
      has been used as a sensitive marker of brain damage. Previous studies have found
      alterations in peripheral S100B levels in schizophrenic patients on medication.
      We compared serum S100B levels of 20 medication-free DSM-IV schizophrenic
      patients and 20 age-gender matched healthy controls. Schizophrenic patients
      presented higher serum S100B levels (mean 0.120 ng/ml+/-S.D. 0.140) compared to
      controls (mean 0.066 ng/ml+/-S.D. 0.067; P=0.014) and there was a negative
      correlation with illness duration (r=-0.496, P=0.031). The results of this study
      indicate that serum S100B levels may be a state marker of a limited
      neurodegenerative process, particularly in the early course of schizophrenia or,
      at least, in a subgroup of schizophrenic patients.

PMID- 11287052
TI  - No deficit in total number of neurons in the prefrontal cortex in schizophrenics.
AB  - The prefrontal cortex (PFC), defined as the cortical region which has the major
      reciprocal connections with the mediodorsal thalamic nucleus (MD), has often been
      implicated in schizophrenia. Morphometric studies have shown altered neuronal
      density and structure in parts of the PFC in schizophrenic brains. In addition,
      the MD and nucleus accumbens have shown a significant deficit in total neuron
      number. The purpose of the present study was to estimate the total neuron number
      in the PFC in schizophrenics and controls. Using a stereological design, the PFC
      was studied in eight brains from schizophrenic patients and 10 age-matched
      control brains. The bilateral average total number of neurons in the PFC was
      estimated to be 2.76 x 10(9) (CV=S.D./mean=0.15) in the schizophrenic brains
      whereas that of controls was a non-significantly different value of 3.11 x 10(9)
      (CV=0.22; P=0.23). Furthermore, no significant differences were found between the
      two groups in neuronal density (P=0.10) or volume of the PFC (P=0.49). It is of
      course possible that a neuronal deficit, which cannot be revealed when estimating
      the total global number of neurons in the whole PFC, might exist in a subregion
      of the PFC. In conclusion, uniform loss of neuronal soma in the PFC does not
      appear to constitute the neural substrate of the pathological process in
      schizophrenia.

PMID- 11287053
TI  - Plasma homovanillic acid in untreated schizophrenia--relationship with
      symptomatology and sex.
AB  - Plasma homovanillic acid (pHVA) concentrations are considered to reflect, in
      part, central dopamine metabolism and thus may be of value in assessing the role
      of dopamine neurotransmission in schizophrenia. Furthermore, some recent studies
      have suggested a relationship of pHVA with symptomatology. We have undertaken a
      study of pHVA in a large cohort of unmedicated DSM-IV schizophrenic patients in
      order to assess the relationship of pHVA to various clinical parameters. pHVA in
      58 drug-free patients (10.11+/-0.52 ng/ml) was significantly elevated in
      comparison with 62 matched control subjects (8.77+/-0.39 ng/ml). pHVA was found
      to be higher in patients with a more negative syndrome. No significant
      correlation of pHVA with overall SAPS or SANS scores was apparent in the patients
      although, within the SANS subscales, a significant relationship to anhedonia
      asociality was apparent. Interestingly, the male drug-free patients showed a
      correlation of pHVA with negative symptoms defined by SANS and several SANS
      subscales, while females showed no significant relationship with any SANS
      subscales. The results may suggest that an increased dopaminergic turnover is
      apparent in (male) schizophrenic patients with predominantly negative symptoms,
      providing some support for reports that this change in neuronal activity may be
      related to the neuropathological abnormalities seen in the disease, which may
      themselves differ between males and females. Such neuronal deficits of
      developmental or degenerative origin may thus result in an
      elevation/disinhibition of central dopamine metabolism in schizophrenia.

PMID- 11287054
TI  - Effects of the monoamine oxidase A inhibitor moclobemide on hippocampal
      plasticity in GR-impaired transgenic mice.
AB  - A reduction in glucocorticoid receptor (GR) function leads to hippocampus
      dependent allocentric spatial learning deficits, altered novelty exploration and
      disrupted hippocampal long-term potentiation (LTP) in transgenic mice expressing
      a GR antisense construct. After continuous long-term treatment of these mice with
      moclobemide (a reversible inhibitor of monoamine oxidase A), spatial navigation
      performance but not accuracy improved during initial acquisition. These changes
      were associated with a shift of the threshold for the induction of hippocampal
      LTP at low stimulation frequencies. Moreover, novel object exploration increased
      in both control and transgenic animals following long-term treatment with
      moclobemide. These findings open the possibility that antidepressants might
      improve hippocampal function under conditions of impaired stress hormone
      regulation, and that these drugs might in part act through this mechanism to
      attenuate cognitive deficiency in disorders such as depression.

PMID- 11287055
TI  - Enhanced long-latency somatosensory potentials in major depressive disorder.
AB  - Bodily misperceptions are a frequent symptom in major depressive disorder. A
      reduced ability to deflect attention from somatosensory stimuli may contribute to
      the generation of unpleasant bodily sensations and co-occur with altered
      habituation of the brain electric reactions to somatosensory stimuli. The aim of
      the present study was to explore whether attention-related components of
      somatosensory evoked potentials (SSEP) and the habituation of these components
      are altered in major depression. Fifteen patients with major depressive disorder
      were compared to an age- and gender-matched group of 15 healthy controls. A
      series of identical, intrusive but not painful electric stimuli were applied to
      the left index finger for 48 min. Averaged SSEP were computed from multichannel
      EEG recordings for consecutive recording blocks of the experiment, each block
      containing 162 stimuli. Based on these data the habituation process of late
      components of the SSEP was analysed in two latency intervals (50-150, 170-370
      ms). Patients showed significantly enhanced reactions throughout the entire
      experiment. The persistence of enhanced SSEP components throughout the
      habituation process may be caused by a deficit in reducing the activity of
      attention-related brain processes concerned with intrusive, yet behaviourally
      irrelevant, continued stimulation in the state of major depression.

PMID- 11287056
TI  - On the impact of episode sensitization on the course of recurrent affective
      disorders.
AB  - Sensitization of an organism by recurrent disease episodes is postulated as a key
      mechanism governing the progressive long-term course of affective disorders. The
      particular significance is that episode sensitization could underly the
      transition from externally triggered disease episodes to autonomous episode
      generation. Functionally, this transition might be explained by positive feedback
      between a disease episode and the activity state of an organism which includes
      the introduction of a memory trace for generated disease episodes. Here we
      consider the functional consequences of episode sensitization for the course of
      recurrent affective disorders. We use a computational approach and extend our
      previously introduced model for the course of affective disorders by a feedback
      mechanism for episode sensitization. Depending on sensitization timescale and
      amount, triggered episodes leave the model in a sustained sensitized state or
      induce autonomous disease progression. Runaway activation can end in saturation.
      Remarkably, however, over a broad parametric range the progression ends in
      intermediate states with fluctuating disease patterns. This behavior results from
      the model's nonlinear dynamics and represents a situation where the feedback
      intermittently changes between positive and negative directions. Our simulations
      strongly support episode sensitization as an important disease mechanism for
      affective disorders. From a nonlinear standpoint, this mechanism offers an
      explanation not only for autonomous disease progression but also for occurence
      and stability of irregular rapid-cycling disease states.

PMID- 11287058
TI  - Gate questions in psychiatric interviewing: the case of suicide assessment.
AB  - Gate questions are commonly used to shorten structured interviews, by not probing
      negative responses with more detailed questions. This study quantified cases of
      aborted suicide attempts that would have been missed, if we had skipped detailed
      questions following a gate. To accomplish this, we interviewed a random sample of
      135 adult psychiatric inpatients concerning their past suicidal behavior. Using
      our structured interview, subjects were asked a general question about aborted
      suicide attempts, and then asked method-specific questions regardless of their
      response to the general "gate" question. Of the seventy subjects who were found
      to have histories of aborted attempts, 44.3% answered "no" to the gate question.
      Comparing these "false negative" subjects to "true positives," who had answered
      "yes" to the gate question and reported bona fide aborted attempts yielded no
      significant associations with demographics, psychiatric diagnoses, or reported
      histories of actual suicide attempts. Thus, a large number of subjects with
      aborted attempts would have been missed if a negative response to the gate
      question had not been probed. Clinical and reasearch implications generally, as
      well as implications for suicide assessment, are discussed.

PMID- 11287057
TI  - Panic-agoraphobic spectrum: reliability and validity of assessment instruments.
AB  - DSM IV is a simple, reliable diagnostic system with many advantages. However, DSM
      diagnostic criteria may not provide sufficient characterization of clinically
      significant symptoms. We have undertaken a project to assess an array (spectrum)
      of clinical features associated with different DSM Disorders. The purpose of this
      paper is to report on reliability of assessment instruments for Panic-Agoraphobic
      Spectrum (PAS), to document convergent validity of PAS symptom groupings, and to
      confirm the relationship between PAS and DSM IV Panic Disorder (PD). We studied
      22 normal controls and 95 outpatients who met criteria for Panic Disorder with
      and without lifetime Major Depression, and Major Depression or Obsessive
      Compulsive Disorder without lifetime Panic Disorder. Assessment instruments had
      excellent reliability and there was good concordance between interview and self
      report formats. PAS scores were highest in subjects with PD, followed by
      outpatients without PD, and were lowest in normal controls. PAS scores varied
      among PD patients, and a subgroup of patients without PD scored high on PAS. We
      conclude that PAS can be reliably assessed, and that it describes a valid,
      coherent constellation of features associated with DSM IV Panic Disorder, but
      providing additional important clinical information.

PMID- 11287059
TI  - Age-dependent changes in HCNP-related antigen expression in the human
      hippocampus.
AB  - Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from
      the young rat hippocampus, enhances the cholinergic phenotype development of the
      medial septal nucleus in vitro. In this study, we examined the HCNP-antigen
      distribution and the age-related changes in the number of positive cells in the
      hippocampus (obtained at autopsy from 74 subjects with no known neurological
      disorders). Immunohistochemical assay revealed that the immunopositive cells were
      GABAergic neurons and oligodendrocytes. They were first identified in the fetus
      at around 25 to 30 weeks and their number increased rapidly with advancing
      postconceptional age to reach maximal at the perinatal stage and in early
      postnatal life; it then decreased to the adult level by 10 years old. These
      results suggest that HCNP-related antigen may play important roles in the
      development and/or differentiation of the human hippocampus.

PMID- 11287060
TI  - Muscarinic acetylcholine receptors in the normal, developing and regenerating
      newt retinas.
AB  - Immunoreactivity for m2 and m4 muscarinic acetylcholine receptors (mAChRs) was
      demonstrated in the adult newt retina. The m2 mAChR was localized to somata on
      either side of the inner plexiform layer (IPL), especially ganglion cells, and
      also distributed into two bands within the IPL. The distal band at a depth of 0
      15% IPL co-localized with one of two choline acetyltransferase (ChAT)
      immunoreactive bands, while the proximal band at 85-100% depth did not overlap
      with either of the ChAT-ir bands. The m4 mAChR was localized to somata closely
      apposed to either side of the IPL, probably amacrine cell somata, and no
      immunoreactivity was detectable throughout the IPL. The time course of appearance
      of the m2 and m4 mAChRs was examined in both developing and regenerating retinas.
      Like acetylcholinesterase (AChE), the m2 was first detected in somata located at
      the most proximal level of the retina well before ChAT-ir cholinergic neurons
      appeared, while the m4 was detected at the time of appearance of ChAT, in both
      developing and regenerating retinas. When the outer plexiform layer (OPL) began
      to form, somata in the horizontal cell layer became transiently immunoreactive to
      the m2. The discrepancy in distribution of the m2 and ChAT in the IPL suggests
      that mAChR may play a role other than cholinergic neurotransmission. Furthermore,
      the similarity in time course of appearance of the m2 and m4, as well as other
      cholinergic system components [4], in both developing and regenerating retinas
      would suggest that the mechanisms that control neuronal differentiation during
      retinal development and regeneration are similar.

PMID- 11287061
TI  - Stress-induced alterations in locus coeruleus gene expression during ontogeny.
AB  - Brainstem noradrenergic neurons, particularly the locus-coeruleus (LC), play a
      pivotal role in modulating the central stress response and have been implicated
      in regulating the hypothalamic-pituitary-adrenal (HPA) axis. In adult rats, acute
      stress causes an increase in LC firing and tyrosine hydroxylase (TH) gene
      expression. While the role of the LC-norepinephrine (LC-NE) system in the adult
      stress response has been well characterized, there is limited evidence for its
      participation during development. Previous studies described the neonatal HPA
      axis as hyporeactive because of stimulus-selective pituitary activation. However,
      maternal deprivation does reinstate stress-induced endocrine activity and can
      amplify the neural stress response. Considering that LC neurons can modulate
      neuroendocrine activity, we hypothesized that the LC-NE system would be stress
      responsive during development. Because maternal deprivation (DEP) can alter the
      central stress response, we examined the LC-NE stress response in both DEP and
      non-deprived (NDEP) pups. Following an isotonic saline injection (stressor) the
      time course of TH, c-fos and glucocorticoid receptor (GR) mRNA was examined.
      Stress-induced TH mRNA was increased in DEP pups at postnatal day (pnd) 12 and in
      both NDEP and DEP pups at pnd 18. At 15, 30 and 240 min c-fos mRNA was markedly
      increased in all groups examined. GR mRNA was not altered at pnd 12; however, at
      pnd 18 NDEP pups showed reduced GR mRNA expression. These data indicate that
      during ontogeny the LC-NE system is stress-responsive to an acute mild challenge.
      Activation of LC-NE neurons suggests that this system may participate in
      modulating the neuroendocrine stress response during development.

PMID- 11287062
TI  - Effects of age and clustered hypoxia on [(125)I] substance P binding to
      neurotachykinin-1 receptors in brainstem of developing swine.
AB  - This work focused on the postnatal development of substance P-bound
      neurotachykinin-1 (NK-1) receptors in the porcine brainstem using 2-3-, 6-11-, 16
      18-, and 21-28-day-old piglets versus adult, and on alterations in these
      receptors after single and six-daily repeated clustered hypoxia using 6-11- and
      21-28-day-old piglets. NK-1 receptor localization and densities were determined
      by quantitative autoradiography using mono-iodinated Bolton-Hunter substance P
      ([(125)I]BHSP). Slide-mounted brainstem sections, incubated in [(125)I]BHSP and
      then exposed to film, have shown [(125)I]BHSP binding throughout many brainstem
      nuclei and tracts, including the ambigual/periambigual (nAmb), dorsal motor vagal
      (dmnv), gigantocellular (nGC), hypoglossal (nHyp), medial parabrachial (nPBM),
      lateral reticular (nRL), raphe magnus (nRMg), raphe obscurus (nROb) and solitary
      tract (nTS) nuclei. NK-1 receptor densities decreased with age. As compared to
      normoxia, NK-1 receptor densities increased significantly after the six-daily
      hypoxia protocol in nAmb, dmnv, nHyp, nRL, nRMg, nROb, and nTS of both the young
      and older age groups. This increase may represent receptor upregulation as an
      adaptation to repeated hypoxia.

PMID- 11287063
TI  - Neuronal synthesized insulin roles on neural differentiation within fetal rat
      neuron cell cultures.
AB  - We previously, described the production and secretion of insulin by fetal neurons
      in culture and demonstrated that neuronal synthesized insulin [I(n)] promoted
      neurofilament distribution and axonal growth. In this study we investigated the
      role of I(n) in promoting neural differentiation. Stem cells from 16 day
      gestational age rat brains were cultured in an insulin-free defined medium (IFDM)
      and treated with: 5, 20 or 100 ng/ml of exogenous insulin, 100 ng/ml insulin-like
      growth factor I (IGF-I) or an anti-insulin antibody. The neurons were studied at
      1 and 3 days of incubation. The total number of cells showed no significant
      difference (P>0.05) in any of the media used, except the IFDM at day 3 of
      incubation treated with the anti-insulin antibody (P<0.05) and IGF-I to 20 ng/ml
      of insulin (P<0.05). No significant difference (P>0.05) was found in the number
      of differentiated neurons incubated in the IFMD, in which the neurons produce and
      secrete I(n), between days 1 and 3 of incubation, but neural differentiation
      decreased significantly (P<0.05) when treated with the anti-insulin antibody.
      Exogenous insulin significantly increased (P<0.05) the number of differentiated
      neurons compared to the IFDM. A significant reduction (P<0.05) of differentiated
      neurons was observed at day 3 of incubation with IGF-I compared to all the
      different media. Thus, I(n) has a role in promoting neural differentiation and
      growth, but exogenous insulin promoted neural differentiation and growth beyond
      I(n).

PMID- 11287064
TI  - Ontogeny of brain-derived neurotrophic factor gene expression in the forebrain of
      prairie and montane voles.
AB  - Brain-derived neurotrophic factor (BDNF) plays an important role in normal brain
      development. In the present study, we examined the ontogenetic pattern of BDNF
      gene expression in both monogamous prairie voles (Microtus ochrogaster) and
      promiscuous montane voles (M. montanus); two closely related microtine rodents
      that differ in life strategy and social behavior. In both species, BDNF mRNA
      showed an early appearance and a transient expression in a regionally specific
      manner. In the dentate gyrus and CA3 region of the hippocampus, BDNF mRNA was
      found neonatally, increased gradually during development, and reached a peak at
      weaning, followed by a subsequent decline to the adult level. In the
      paraventricular nucleus of the hypothalamus, levels of BDNF mRNA persisted until
      weaning, followed by a significant increase to the adult levels at 3 months of
      age. BDNF mRNA also demonstrated a species-specific developmental pattern. In the
      cingulate cortex, BDNF mRNA labeling displayed a transient increase in the second
      and third postnatal weeks followed by a subsequent decrease to the adult level in
      prairie voles, but persisted throughout the course of development in montane
      voles. In general, montane voles achieved an adult pattern of BDNF mRNA
      expression earlier than did prairie voles. Together, these data indicate that
      BDNF may function differently in infant and adult brains, and that the two
      species of voles differ in the ontogenetic pattern of BDNF mRNA expression in a
      regional-specific manner, which may be associated with their different life
      strategy and brain and behavioral development.

PMID- 11287065
TI  - Apoptosis in cultured hNT neurons.
AB  - Programmed cell death (apoptosis) is an important mechanism shaping the size of
      different cell populations within the developing nervous system. In our study we
      used the NT2/D1 clone originally established from the Ntera 2 cell line to
      investigate the baseline levels of apoptosis in cultured postmitotic hNT (NT2-N)
      neurons previously treated for 3, 4 or 5 weeks with retinoic acid (RA) and
      compared it with apoptosis in NT2 precursors unexposed to RA. First, we examined
      whether different lengths of exposure to RA might affect baseline apoptotic rate
      in differentiating hNT neurons. Second, we investigated whether cultured hNT
      neurons, previously shown to possess dopaminergic characteristics, would be
      preferentially affected by apoptosis. Using the terminal deoxynucleotidyl
      transferase (tdt)-labeling technique we found that the postmitotic hNT neuronal
      cells exposed to RA demonstrated significantly higher numbers of apoptotic cells
      (12.5-15.8%) in comparison to rapidly dividing NT2 precursor cell line (3.6-4.4%)
      at both studied (1 and 5 days in vitro, DIV) time points. Similar apoptotic
      nuclear morphology, including a variable extent of nuclear fragmentation was
      observed in all examined hNT cultures. On the other hand, the incidence of
      apoptotic nuclei was rare in cultures of NT2 precursors not subjected to RA
      treatment. Combined immunocytochemistry for tyrosine hydroxylase (TH) and Hoechst
      staining revealed dopaminergic hNT neurons destined to die. Our double-labeling
      studies have demonstrated that only a subset of TH-positive hNT cells had
      condensed chromatin after 1 (approx. 15%) and 5 (approx. 20%) DIV. NT2 precursors
      were not TH-positive. Collectively, our results demonstrated that exposure to
      differentiating agent RA triggers an apoptotic commitment in a subset of
      postmitotic hNT neurons. These results suggest that this cell line may serve as a
      model of neuronal development to test various pathogenic factors implicated in
      the etiology of Parkinson's disease (PD), as well as to screen numerous
      pharmacological treatments that may slow or prevent dopaminergic deterioration.

PMID- 11287066
TI  - Paradoxical effects of ketamine on the memory of fetuses of different ages.
AB  - Brain N-methyl-D-aspartate (NMDA) glutamate receptors have been implicated as
      important mediators of both learning and neuronal development. The current study
      investigated how ketamine (a well-known NMDA-receptor blocking drug) influences
      taste-mediated conditioned motor responses (CMRs) in perinatal rats. Dams
      pregnant with either embryonic day 18 (E18) or E19 rat fetuses were injected with
      0 or 100 mg/kg ketamine HCl (i.p.). One-half hour later, a reversible spinal
      block was performed on the dam and fetuses received oral lavage with 10 microl,
      0.3% saccharin (SAC) or water (control) in utero. After the oral injection,
      fetuses received either a saline (control) or lithium chloride (LiCl) injection
      (81 mg/kg, i.p.). The uterus was replaced and, 2 days later (E20 or E21), some
      rats received oral lavage with SAC. Other litters were born via normal vaginal
      delivery or Cesarean section and orally exposed to SAC on post-natal day 3 (P3).
      Motor responses were observed immediately after the oral lavage of SAC. If SAC
      had been paired with LiCl in utero, pups generally exhibited conditioned
      suppression of orofacial movements (as compared to controls). Ketamine
      significantly attenuated this taste-mediated CMR of animals conditioned on E19.
      However, the same treatments did not disrupt CMRs of rats treated with ketamine
      before CS-US pairing on E18. Our findings indicate an age-dependent role for NMDA
      receptors in the formation of CMRs in perinatal rats.

PMID- 11287067
TI  - Activity modulates neuronal proliferation in the developing olfactory epithelium.
AB  - The present experiment demonstrates that environmental stimulation can activate
      neurogenesis within olfactory mucosae exhibiting depressed proliferation. Rats
      underwent naris occlusion on P1 with plugs that were removed 20 days later.
      Normal respiration induced a sharp increase in proliferating neuronal precursors
      within 24-48 h, and epithelial depth was restored within 5 days.

PMID- 11287068
TI  - Different developmental profiles of the expression of preprosomatostatin and
      preprotachykinin-A mRNAs in rat SCN neurons.
AB  - The suprachiasmatic nucleus (SCN), a central circadian oscillator of mammals,
      contains various peptides arranged in the compartment specific manner. In the
      present study, we examined a distinct population of neurons in the central part
      of the SCN. In situ hybridization histochemistry has demonstrated that these
      neurons coexpressed both preprosomatostatin (PPSS) and preprotachykinin A (PPT-A)
      mRNAs, but the developmental expression profiles were different among two. PPSS
      mRNA first appeared in the SCN at postnatal day 1(P1). The intensity and number
      of PPSS mRNA signals increased and peaked at P7-P14 and gradually decreased as to
      adult age (P56). However, PPT-A mRNA-positive appeared late at P7, and gradually
      increased up to P56. These findings suggest that neurons encoding both the PPSS
      and PPTA genes first express PPSS and then express PPT-A at a later stage of
      maturation.

PMID- 11287069
TI  - Confirmation of the retinopetal/centrifugal nature of the tyrosine hydroxylase
      immunoreactive fibers of the retina and optic nerve in the weaver mouse.
AB  - The number of tyrosine hydroxylase-immunoreactive fibers in the nerve fiber layer
      is increased in the retina of the weaver compared to control mice (Dev. Brain
      Res. 121 (2000) 113). To confirm the retinopetal/centrifugal nature of these
      fibers, a newly devised whole-mounted optic nerve technique allowed us to
      determine, during development, their first appearance within the optic nerve
      (post-natal day 12) compared to retina (post-natal day 13). One such fiber was
      also observed looping in the retina of a monkey fetus.

PMID- 11287070
TI  - Cell migration to the anterior and posterior divisions of the granule cell layer
      of the accessory olfactory bulb of adult opossums.
AB  - To test the hypothesis that differential addition of new cells occurs in the two
      functionally distinct divisions of the accessory olfactory bulb (AOB), the
      addition of bromodeoxyuridine-labeled cells was analyzed in the anterior and
      posterior subdivisions of the AOB as a function of post-injection survival time
      (0-11 days). One week postinjection, an increase of cells was detected in the
      granule layer but not in the glomerular or mitral/tufted cell layers. No evidence
      for differential addition of cells to the anterior and posterior divisions was
      observed.

PMID- 11287071
TI  - Estradiol alleviates depressive-like symptoms in a novel animal model of post
      partum depression.
AB  - The effect of hormone withdrawal following hormone-simulated "pregnancy" on
      "depressive-like behavior" in the Forced Swim Test (FST) was investigated in
      female Long-Evans rats. Females were randomly assigned to "pregnant",
      "pregnant"+estradiol benzoate (EB), and control groups. Both the "pregnant" and
      "pregnant"+EB groups received daily injections of the hormones estradiol and
      progesterone to simulate the 23-day gestational period in the rat. However, the
      "pregnant"+EB group continued to receive daily estradiol injections after
      "pregnancy". All groups were tested 48 h after the last injection of the
      pregnancy period in the FST and subsequently in the Open Field Test (OFT).
      Results revealed that the "pregnant" rats exhibited significantly increased
      immobility and decreased struggling and swimming behaviors as compared to the
      "pregnant"+EB and control groups. These findings could not be explained by an
      overall depression in general locomotor activity among "pregnant" rats, as the
      "pregnant" rats made more area crossings in the OFT. Thus "pregnant" rats
      exhibited behaviors consistent with "depressive-like" symptoms "post-partum"
      (after their hormone regime was discontinued). Continual treatment with high
      levels of estradiol in the "pregnant"+EB group, however, reversed the exhibition
      of these behaviors. These results imply that withdrawal from chronic high levels
      of pregnancy-associated hormones (estradiol and progesterone) can produce
      depressed symptomology in rodents, which can be prevented by prolonging exposure
      to high levels of estradiol through the post-partum period. These findings are
      the first demonstration of "depressive-like" symptoms in a rodent model of post
      partum pregnancy and the ability of high levels of estradiol to attenuate these
      "depressive-like" symptoms.

PMID- 11287072
TI  - The nature of the conditioned response mediating olfactory conditioned
      ejaculatory preference in the male rat.
AB  - We have developed a model to study the influence of conditioning on sexual
      partner preference in the rat. In this model, pairing a neutral odor (almond)
      with copulation to ejaculation produces a subsequent preference to ejaculate with
      females bearing that odor. We refer to this phenomenon as a conditioned
      ejaculatory preference (CEP). The present study investigates the nature of the
      conditioned response that mediates CEP. Given equal mount and intromission
      distributions, but an unequal ejaculation distribution, we hypothesized that two
      mechanisms could account for CEP: facilitated ejaculation or selective
      ejaculation. To test these hypotheses, we examined the effect of omitting the
      olfactory conditioned stimulus (CS) or applying it to a nonreceptive female.
      Males trained with the CS paired with copulation (paired-trained males) failed to
      display evidence of delayed ejaculation when copulating with unscented females.
      Conversely, paired-trained males displayed CS-elicited copulatory behavior with
      CS-bearing nonreceptive females. In addition, we re-analyzed the data from the
      copulatory preference tests of previous experiments for CEP-displaying males.
      Again, we failed to find evidence of facilitated ejaculation with the scented
      female. However, the time between the last mount or intromission and ejaculation
      was increased if either occurred with the scented female. Furthermore, more
      mounts were directed towards the scented female near the end, but not at other
      points, of an ejaculatory series. These findings suggest that the paired-trained
      males attend to the scented female near the point of ejaculation, and are
      consistent with the hypothesis that CEP is mediated by selective ejaculation.

PMID- 11287073
TI  - Pattern of REM sleep occurrence in continuous darkness following the exposure to
      low ambient temperature in the rat.
AB  - The occurrence of REM sleep episodes, separated by intervals >3 min (single
      episodes) and < or =3 min (sequential episodes), was determined in the rat during
      the recovery (ambient temperature (Ta) 23 degrees C, L period of the LD [12 h:12
      h]-cycle), which followed the exposure to low Ta (0 and -10 degrees C) during the
      D period of the previous LD-cycle, either in normal light (DL) or in continuous
      darkness (DD). Both exposures were characterized by an almost complete
      disappearance of REM sleep, whilst the recoveries showed an increase in the
      amount of REM sleep in the form of sequential episodes, which in DD was
      particularly prominent and concomitant with a decrease in the amount of REM sleep
      in the form of single episodes. The initial 2 h-rate of REM sleep occurrence was
      lower following the exposure to Ta -10 degrees C, than to Ta 0 degrees C. In DD,
      such an effect was due to the large reduction in the occurrence of sequential REM
      sleep episodes. A functional correlate of this finding is that the accumulation
      capacity of a second messenger (cAMP) was found to be lower at the end of the
      exposure to Ta -10 degrees C, with respect to both the control (Ta 23 degrees C)
      and the end of exposure to Ta 0 degrees C, in the preoptic-anterior hypothalamus,
      but not in the cerebral cortex.

PMID- 11287074
TI  - Estrogen attenuates the drinking response induced by activation of
      angiotensinergic pathways from the lateral hypothalamic area to the subfornical
      organ in female rats.
AB  - The present study was carried out to investigate whether estrogen modulates the
      drinking response induced by activation of angiotensinergic neural pathways from
      the lateral hypothalamic area (LHA) to the subfornical organ (SFO) in the female
      rats. Microinjection of ANG II (10(-10) M, 0.2 microl) into the LHA caused
      drinking in 17 out of 26 ovariectomized (OVX) female rats that were treated with
      propylene glycol (PG) vehicle and in 18 out of 28 OVX female rats that were
      treated with estrogen benzoate (EB). In both groups, previous injections of the
      ANG II antagonist saralasin (Sar, 10(-10) M, 0.2 microl) into the SFO
      significantly attenuated the water intake caused by the ANG II injection,
      suggesting that the ANG II-induced drinking response may be mediated by the
      angiotensinergic LHA projections to the SFO. Injections of ANG II (10(-10) M, 0.2
      microl) into the SFO elicited drinking in all the animals that demonstrated the
      drinking response to ANG II injected into the LHA. The amount of water intake
      caused by either the injection of ANG II into the LHA or the SFO was
      significantly greater in the PG-treated than in the EB-treated animals. These
      results suggest that the circulating estrogen may act to attenuate the dipsogenic
      response induced by activation of the angiotensinergic pathways from the LHA to
      the SFO.

PMID- 11287075
TI  - Dissociation of arousal-like from anxiogenic-like actions of brain corticotropin
      releasing factor receptor ligands in rats.
AB  - Behavioral actions of centrally administered corticotropin-releasing factor (CRF)
      are likely subserved by multiple brain targets and functional effector systems.
      The present studies compared effects of two CRF ligands, a full, post-synaptic
      CRF receptor agonist (rat/human CRF(1-41)) and a CRF binding protein ligand
      inhibitor (rat/human CRF(6-33)) in a behavioral testing battery sensitive to
      arousal, fear-like and aversive processes in Wistar rats. The profile of global
      efficacy for the centrally administered CRF receptor agonist was characterized by
      low dose (0.5-1.0 microg) arousal-like effects in locomotor and conditioned
      ambulation contexts and by high dose (5-25 microg) conditioned immobility, taste
      aversion and place aversion. In contrast, a profile of limited efficacy for the
      centrally administered CRF binding protein ligand inhibitor included only dose
      dependent motor activating and facilitation of fear conditioning effects without
      any of the anxiogenic-like or aversive properties of CRF agonist administration.
      These results suggest that arousal-like activation is a fundamental,
      physiologically relevant consequence of brain CRF system stimulation whereas
      aversive and anxiety-like effects reflect pharmacological actions of a CRF
      receptor agonist.

PMID- 11287076
TI  - Differential effect of Fyn tyrosine kinase deletion on offensive and defensive
      aggression.
AB  - Fyn tyrosine kinase is highly expressed in the limbic system and mice lacking Fyn
      tyrosine kinase showed increased fearfulness in a variety of tests for anxiety
      related behaviors. To investigate the possible role of Fyn tyrosine kinase in
      aggression, we assessed the aggressive behaviors of the mice lacking the Fyn
      tyrosine kinase using the resident-intruder and restraint-induced target biting
      paradigms. The percentage of Fyn-deficient mice that attacked an inanimate target
      in a restraint tube was higher than that of the control mice. On the contrary, in
      the resident-intruder paradigm, the percentage of Fyn-deficient mice that
      attacked the intruder was lower and the Fyn-deficient mice showed a longer
      latency to attack an intruder. These results suggest a distinct role of Fyn
      tyrosine kinase in enhancing the offensive aggression and decreasing the
      defensive aggression. A possible influence of anxiety-phenotype of the Fyn
      deficient mice on their abnormal aggressive behavior was discussed.

PMID- 11287077
TI  - Role of right hemifield in visual control of approach to target in zebrafish.
AB  - When a zebrafish has to choose between two identical stimuli (e.g. a conditioned
      stimulus, CS, for food reward), it tends to respond to the one on its right.
      Errors are more numerous when reinforced for taking the one on the left rather
      than the one on the right. When trained to a single medial stimulus, and
      presented in non-reinforced probe trials with a pair of identical stimuli, the
      one on the right is chosen. Use by zebrafish of right eye (RE), viewing to
      control a planned motor response, extends from objects that are to be bitten to a
      choice of one of two routes. When the CS is visible behind a barrier of vertical
      bars, so that it can be approached around either end, it is the right end that is
      chosen. Standing motor bias independent of the nature of the task can be
      excluded. Other vertebrates show RE control of response. Toads are more likely to
      take food seen with the RE. The domestic chick uses the RE in visual control of
      approach to an object that has to be manipulated with the bill. RE control of use
      of the mouth in a fish shows that that this is an earlier condition than
      lateralised control of bilateral effectors like hands.

PMID- 11287078
TI  - Effects of dorsal and ventral striatal lesions on delayed matching trained with
      retractable levers.
AB  - Recent evidence has suggested that thalamic amnesia results from damage to the
      intralaminar nuclei, an important source of input to striatum. To test the
      hypothesis that intralaminar damage disrupts functions mediated by striatum, we
      studied the effects of striatal lesions on a delayed matching task known to be
      affected by intralaminar lesions. Rats were trained to perform the task and given
      one of five treatments: sham surgery or a lesion of medial or lateral
      caudate/putamen, nucleus accumbens, or ventral striatum. Rats with ventral
      striatal lesions were impaired compared to all other groups. Rats with medial
      caudate/putamen or nucleus accumbens lesions were impaired compared to controls.
      The effects of ventral striatal lesions were sufficient to account for
      impairments in the accuracy and latency of delayed matching responses observed in
      previous studies of intralaminar and medial frontal cortical lesions. The ventral
      striatal lesions involved portions of ventral pallidum and thus it seems likely
      that they affected functions mediated by the nucleus accumbens as well as
      striatal areas of the tubercle. Serial reversal learning trained in the same
      apparatus with the same reinforcer was unaffected by all of the lesions. These
      results are discussed in terms of the roles of midline thalamic nuclei and of
      thalamo-cortico-striatal circuits in delayed conditional discrimination tasks.

PMID- 11287079
TI  - Motor behavioural changes after intracerebroventricular injection of 6
      hydroxydopamine in the rat: an animal model of Parkinson's disease.
AB  - At the beginning of the 1970s, different studies reported behavioural
      disturbances after the intracerebroventricular (icv) administration of 6
      hydroxydopamine (6-OHDA) in the rat. Despite the fact that this neurotoxic agent
      degenerates brain dopaminergic (DA-) cells, its potential utility to produce a
      rat model of Parkinson's disease (PD) was never systematically studied because
      the aphagia and adipsia were often observed. In the present study, a procedure
      that induces a marked DA-cell degeneration that bypasses these and other
      undesirable complications of icv injection of 6-OHDA is reported. Lesioned
      animals (50-500 microg of 6-OHDA) showed a persistent motor syndrome composed of
      hypokinesia, purposeless chewing and catalepsy. The intensity of motor signs was
      dose-dependent, and recovered partially after administration of DA-receptor
      agonists, exposure to sensorial stimuli and stress, three procedures that reduce
      motor dysfunctions in Parkinson's disease (PD). Lesioned animals showed bilateral
      and symmetrical midbrain DA-cell degeneration with the highest cell-loss in A9
      group (substantia nigra), followed by A8 (retrorubral field) and A10 (ventral
      tegmental area) groups. The similarity between the behavioural syndrome and the
      topographical profile of cell-loss after icv injection of 6-OHDA in rats and the
      clinical and neuropathological features of PD indicates that this may be a
      convenient animal model of PD particularly useful for checking in rats the
      possible efficacy of new anti-parkinsonian drugs on specific parameters of motor
      dysfunctions.

PMID- 11287080
TI  - Pivagabine effects on neuroendocrine responses to experimentally-induced
      psychological stress in humans.
AB  - Neuroendocrinology of chronic stress seems to be characterized by HPA axis
      hyperactivity and early childhood stressors have been hypothesized to predispose
      individuals to adult onset depression by means of dysregulation of the HPA axis.
      Pivagabine (PVG), a hydrophobic 4-aminobutyric acid derivative, has been used
      experimentally recently in the treatment of different disorders related to stress
      maladaptation, because of its possible inhibitory action on corticotrophin
      releasing factor secretion and HPA axis function. In the present study, 20
      healthy male subjects were each exposed twice to the same psychosocial stressor
      (stroop color-word interference task, public speaking and mental arithmetic in
      front of an audience) during a first session (day 1) and a second session (day
      8). Plasma concentrations of norepinephrine (NE), epinephrine (EPI),
      adrenocorticotropic hormone (ACTH) and cortisol (CORT), heart rate (HR) and
      systolic blood pressure (SBP) were measured immediately before the beginning of
      the tests and at their end, 30 min later, on both experimental days. Utilizing a
      double blind schedule, the subjects received pivagabine (900 mg, twice a day)(PVG
      group: nine subjects) or placebo (PBO group: 11 subjects) during the 7 days
      between the two stress sessions. NE, EPI, ACTH, and CORT levels were
      significantly elevated after stress exposure on day 1 and day 8 in PBO group
      subjects. After PVG treatment, on day 8, ACTH, CORT, NE and EPI responses to
      stress were significantly blunted, together with HR and SBP, in PVG group
      subjects. These results add to the evidence concerning PVG capacity to inhibit
      the HPA axis in humans, in response to stressful stimuli, and suggest that the
      action of PVG may be mediated not only by GABAergic receptors, but also by the
      suppression of catecholamines response. PVG treatment could modulate HPA hyper
      responsiveness to stress in subjects with negative affectivity and depressive
      traits.

PMID- 11287081
TI  - Effect of the beta(2)-agonist clenbuterol on the locomotor activity of rat
      submitted to a 14-day period of hypodynamia-hypokinesia.
AB  - The beta(2)-adrenergic agonist clenbuterol is known for its anabolic action on
      normal and atrophied muscles. The aim of this work was to evaluate if chronic
      clenbuterol administration could prevent alterations in the locomotor activity
      induced by hindlimb suspension. The effects of clenbuterol were evaluated in
      three studies: muscle morphological characteristics, observation of locomotor
      movement and electromyographic activity of soleus and gastrocnemius muscles. Rats
      were divided into four groups: control (CON, morphological study only), hindlimb
      suspended (HS), clenbuterol administered (CB, 2 mg kg(-1) per day in drinking
      water), and hindlimb suspended+clenbuterol administered (HSCB). The soleus muscle
      weight was reduced in the two suspended groups (HS and HSCB) but did not change
      after clenbuterol treatment. By contrast, the gastrocnemius weight was not
      affected by suspension but was increased by clenbuterol (CB and HSCB). Some
      locomotor deficits were always observed in HS rats (unstable gait, ankle
      hyperextension, ellipsis). Clenbuterol administration did not prevent these
      perturbations. Cycle duration and soleus burst duration were increased in the
      three groups. Soleus mean EMG (burst area/duration) was decreased in HS rats, but
      not in the two other groups. For the gastrocnemius, burst duration was increased
      in CB rats, decreased in HSCB rats and unchanged in HS ones; mean EMG did not
      change. In conclusion, clenbuterol cannot be used as a countermeasure to reduce
      the alteration in locomotor performance. Moreover, our results suggest that this
      alteration is specifically related to changes in neuronal properties.

PMID- 11287083
TI  - Origins of the many NPY-family receptors in mammals.
AB  - The NPY system has a multitude of effects and is particularly well known for its
      role in appetite regulation. We have found that the five presently known
      receptors in mammals arose very early in vertebrate evolution before the
      appearance of jawed vertebrates 400 million years ago. The genes Y(1), Y(2) and
      Y(5) arose by local duplications and are still present on the same chromosome in
      human and pig. Duplications of this chromosome led to the Y(1)-like genes Y(4)
      and y(6). We find evidence for two occasions where receptor subtypes probably
      arose before peptide genes were duplicated. These observations pertain to the
      discussion whether ligands or receptors tend to appear first in evolution. The
      roles of Y(1) and Y(5) in feeding may differ between species demonstrating the
      importance of performing functional studies in additional mammals to mouse and
      rat.

PMID- 11287084
TI  - NPY in invertebrates: molecular answers to altered functions during evolution.
AB  - As in Lymnaea stagnalis NPY plays a key role in regulating energy flows but has
      no effect on food intake, two important questions arise: 1) How is the amount of
      food consumed related to energy storage? 2) Can we give a molecular explanation
      for this alteration in function of NPY during evolution? Recent data have shown
      that also in Lymnaea a leptin-like factor is produced by glycogen storing cells
      which inhibits food intake, a Lymnaea storage feedback factor (LySFF). So, food
      consumption seems in balance with the amount of energy stored in this animal. We
      suppose that NPY neurons in Lymnaea have receptors for LySFF so that their
      activity in regulating energy homeostasis reflects the amount of stored energy.
      By comparing the molecular structure of NPYs in invertebrates it became clear
      that only molluscan and arthropod NPY are synthesized from a prohormone similar
      to vertebrate NPYs and should be considered as real invertebrate homologs of NPY.
      Based on pharmacological data we suppose that the identified Lymnaea NPY receptor
      is a Y1 subtype. This might explain that LyNPY has no effect on food intake in
      Lymnaea as this function of NPY in mammals is regulated through the Y5 subtype
      receptor.

PMID- 11287085
TI  - Anomalous rates of evolution of pancreatic polypeptide and peptide tyrosine
      tyrosine (PYY) in a tetraploid frog, Xenopus laevis (Anura:Pipidae).
AB  - The South African clawed frog Xenopus laevis is believed to have arisen as a
      result of a tetraploidization event occurring approximately 30 million years ago.
      Two molecular forms of pancreatic polypeptide (PP) have been isolated from an
      extract of the pancreas of this species and two molecular forms of peptide
      tyrosine-tyrosine (PYY) from the intestine. Despite the fact that the amino acid
      sequence of PP has, in general, been very poorly conserved during the evolution
      of tetrapods (only Pro(5), Pro(8), Gly(9), Ala(12), Tyr(27), Arg(33) and Arg(35)
      are invariant among species studied so far), the two Xenopus PPs differ by only a
      single amino acid substition (Asp(22)-->Glu). In contrast the two molecular forms
      of PYY differ by six amino acid substitutions (Glu(15)-->Gln, Thr(18)-->Ala,
      Leu(21)-->Met, Ile(22)-->Thr, Ile(28)-->Val, Val(31)-->Ile). The data imply that
      strong evolutionary pressure is acting to conserve the functional domain in both
      genes encoding PP and so suggest that PP may have an important physiological role
      in amphibians (although the nature of this role has yet to be determined). The
      more rapid mutation of the functional domain in the genes encoding PYY, a peptide
      whose amino acid sequence has been quite well conserved in tetrapods and whose
      physiological significance is well established, suggests that one of the PYY
      genes may be evolving towards a new function or towards becoming a pseudogene.

PMID- 11287086
TI  - Characterization and distribution of neuropeptide Y in the brain of a caecilian
      amphibian.
AB  - Neuropeptide Y (NPY) from the brain of an amphibian from the order Gymnophiona
      (the caecilian, Typhlonectes natans) was characterized. We cloned a 790 base pair
      cDNA encoding the caecilian NPY precursor. The open reading frame consisted of
      291 bases, indicating an NPY precursor of 97 amino acids. Both deduced and
      isolated NPY primary structures were Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu(10)
      Asp-Ala-Pro-Ala-Glu-Asp-Met-Ala-Lys-Tyr(20)-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn
      Leu(30)-Ile-Thr-Arg-Gln-Arg-Tyr. NH2. In caecilian brain, we observed NPY
      immunoreactive cells within the medial pallium, basal forebrain, preoptic area,
      midbrain tegmentum and trigeminal nucleus. The prevalence of preoptic and
      hypothalamic terminal field staining supports the hypothesis that NPY controls
      pituitary function in this caecilian.

PMID- 11287087
TI  - Characterization of neuropeptide Y Y1-like and Y2-like receptor subtypes in the
      mouse brain.
AB  - To characterize receptor subtypes in the mouse, we performed autoradiographic
      localization and pharmacological characterization studies using the selective
      radiolabeled agonists, [(125)I]-Leu(31), Pro(34)-PYY and [(125)I]-PYY 3-36. The
      pharmacology of [(125)I]-Leu(31), Pro(34)-PYY and [(125)I]-PYY 3-36 binding to
      mouse brain homogenates were consistent with Y1-like and Y2-like receptors,
      respectively. Using receptor autoradiography, high Y1-like binding was observed
      in the islands of Calleja and dentate gyrus. [(125)I]-PYY 3-36 binding was
      highest in the hippocampus, lateral septum, stria terminalis of the thalamus, and
      compacta and lateralis of the substantia nigra. In addition, there are
      differences in receptor distribution in mouse brain compared to other species
      that may translate into different functional roles for the NPY receptors within
      each species.

PMID- 11287089
TI  - Studies of the human, rat, and guinea pig Y4 receptors using neuropeptide Y
      analogues and two distinct radioligands.
AB  - The neuropeptide Y-family receptor Y4 differs extensively between human and rat
      in sequence, receptor binding, and anatomical distribution. We have investigated
      the differences in binding profile between the cloned human, rat, and guinea pig
      Y4 receptors using NPY analogues with single amino acid replacements or deletion
      of the central portion. The most striking result was the increase in affinity for
      the rat receptor, but not for human or guinea pig, when amino acid 34 was
      replaced with proline; [Ahx(8-20),Pro(34)]NPY bound to the rat Y4 receptor with
      20-fold higher affinity than [Ahx(8-20)]NPY. Also, the rat Y4 tolerates alanine
      in position 34 since p[Ala(34)]NPY bound with similar affinity as pNPY while the
      affinity for hY4 and gpY4 decreased about 50-fold. Alanine substitutions in
      position 33, 35, and 36 as well as the large loop-deletion, [Ahx(5-24)]NPY,
      reduced the binding affinity to all three receptors more than 100-fold. NPY and
      PYY competed with (125)I-hPP at Y4 receptors expressed in CHO cells according to
      a two-site model. This was investigated for gpY4 by saturation with either
      radiolabeled hPP or pPYY. The number of high-affinity binding-sites for (125)I
      pPYY was about 60% of the receptors recognized by (125)I-hPP. Porcine
      [Ala(34)]NPY and [Ahx(8-20)]NPY bound to rY4 (but not to hY4 or gpY4) according
      to a two-site model. These results suggest that different full agonists can
      distinguish between different active conformations of the gpY4 receptor and that
      Y4 may display functional differences in vivo between human, guinea pig, and rat.

PMID- 11287088
TI  - Cloning and characterization of Rhesus monkey neuropeptide Y receptor subtypes.
AB  - Neuropeptide Y (NPY) is a 36 amino acid peptide that is abundant in the brain and
      peripheral nervous system. NPY has a variety of effects when administered into
      the brain including a pronounced feeding effect, anxiolysis, regulation of
      neuroendocrine axes and inhibition of neurotransmitter release. These effects are
      mediated by up to 6 G protein coupled receptors designated Y1, Y2, Y3, Y4, Y5 and
      y6. To better understand the phylogeny and pharmacology of NPY in non-human
      primates, we have cloned and expressed the NPY Y1, Y2 and Y5 receptor subtypes
      from the Rhesus monkey. No cDNA sequence encoding a Y4 receptor was found
      suggesting substantial sequence differences when compared to the human sequence.
      Comparison of these sequences with those from human indicated strong sequence
      conservation of Y1, Y2 and Y5 between the two species. The displacement of (125)I
      PYY binding to the Rhesus monkey and human receptors by various peptides was
      compared to evaluate the pharmacology of the two species. Similar pharmacologies
      were noted across the species at the various receptor subtypes. These results
      indicate the Rhesus monkey and human NPY receptor subtypes have a close amino
      acid sequence conservation and that the peptide recognition domains are conserved
      as well.

PMID- 11287090
TI  - Cloning and characterization of the guinea pig neuropeptide Y receptor Y5.
AB  - The Y5 receptor has been postulated to be the main receptor mediating NPY-induced
      food intake in rats, based on its pharmacological profile and mRNA distribution.
      To further characterize this important receptor subtype, we isolated the Y5 gene
      in the guinea pig, a widely used laboratory animal in which all other known NPY
      receptors (Y1, Y2, Y4, y6) [2,13,33,37] have recently been cloned by our group.
      Our results show that the Y5 receptor is well conserved between species; guinea
      pig Y5 displays 96% overall amino acid sequence identity to human Y5, the highest
      identity reported for any non-primate NPY receptor orthologue, regardless of
      subtype. Thirteen of the twenty substitutions occur in the large third
      cytoplasmic loop. The identities between the guinea pig Y5 receptor and the dog,
      rat, and mouse Y5 receptors are 93%, 89%, and 89% respectively. When transiently
      expressed in EBNA cells, the guinea pig Y5 receptor showed a high binding
      affinity to iodinated porcine PYY with a dissociation constant of 0.41 nM.
      Competition experiments showed that the rank order of potency for NPY-analogues
      was PYY = NPY = NPY2-36 > gpPP > rPP >> NPY 22-36. Thus the pharmacological
      profile of the guinea pig Y5 receptor agrees well with that reported for the Y5
      receptor from other cloned species.

PMID- 11287091
TI  - Y-receptor affinity modulation by the design of pancreatic
      polypeptide/neuropeptide Y chimera led to Y(5)-receptor ligands with picomolar
      affinity.
AB  - Neuropeptide Y (NPY) and pancreatic polypeptide (PP) bind to the Y-receptors with
      very different affinities: NPY has high affinity for the receptors Y(1), Y(2) and
      Y(5), while PP binds only to Y(4)-receptor with picomolar affinity. By exchanging
      of specific amino acid positions between the two peptides, we developed 38 full
      length PP/NPY chimeras with binding properties that are completely different from
      those of the two native ligands. Pig NPY (pNPY) analogs containing the segment 19
      23 from human PP (hPP) bound to the Y-receptors with much lower affinity than NPY
      itself. The affinity of the hPP analog containing the pNPY segments 1-7 and 19-23
      was comparable to that of pNPY at the Y(1)- and Y(5)-receptor subtypes, and to
      that of hPP at the Y(4)-receptor. Furthermore, the presence of the segments 1-7
      from chicken PP (cPP) and 19-23 from pNPY within the hPP sequence led to a ligand
      with IC(50) of 40 pM at the Y(5)-receptor. This is the most potent Y(5)-receptor
      ligand known so far, with 15-fold higher affinity than NPY.

PMID- 11287092
TI  - Neuropeptide Y Y2 receptor signalling mechanisms in the human glioblastoma cell
      line LN319.
AB  - Neuropeptide Y (NPY) regulates neurotransmitter release through activation of the
      Y2 receptor subtype. We have recently characterized a human glioblastoma cell
      line, LN319, that expresses exclusively NPY Y2 receptors and have demonstrated
      that NPY triggers transient decreases in cAMP and increases in intracellular
      calcium responses. The present study was designed to further characterize calcium
      signalling by NPY and bradykinin (BK) in LN319 cells. Both agonists elevated free
      intracellular calcium ([Ca(2+)](i)) without soliciting calcium influx. NPY
      appeared to activate two distinct signalling cascades that liberate calcium from
      thapsigargin- and ryanodine-insensitive compartments. One pathway proceeded
      through phospholipase C (PLC)-dependent phosphatidylinositol turnover, while the
      other triggered calcium release through a so far unidentified mediator. Part of
      the response was sensitive to pertussis toxin (PTX) under conditions where the
      toxin totally abolished the NPY-mediated effects on cAMP. The calcium release
      induced by BK on the other hand was largely PTX-insensitive, PLC-dependent, and
      from both thapsigargin- and ryanodine-sensitive stores. Following stimulation
      with NPY, subsequent [Ca(2+)](i) responses to NPY were strongly depressed.
      Partial heterologous desensitization occurred, when BK was used as the first
      agonist, whereas NPY had no effect on a subsequent stimulation with BK. These
      data suggest that NPY-induced calcium mobilization in LN319 cells involves two
      different G proteins and signalling mediators, and a hitherto unidentified
      calcium compartment. Homologous desensitization of NPY signalling might be
      explained by receptor-G protein uncoupling, while heterologous desensitization by
      BK could be the result of either transient depletion or inhibition of a mediator
      in the calcium signalling cascades activated by NPY.

PMID- 11287093
TI  - Limited signal transduction repertoire of human Y(5) neuropeptide Y receptors
      expressed in HEC-1B cells.
AB  - In HEC-1B cells transfected with human Y(5) neuropeptide Y (NPY) receptors (but
      not in non-transfected cells) NPY inhibited forskolin-stimulated cAMP
      accumulation in a pertussis toxin-sensitive manner (-log EC(50) 8.88 +/- 0.25).
      Elevations of intracellular Ca(2+) were largely restricted to very high NPY
      concentrations and similar in transfected and nontransfected cells. NPY did not
      increase inositol phosphate accumulation and did not activate a variety of
      isoforms of protein kinase C or mitogen-activated protein kinases. We conclude
      that at least upon expression in HEC-1B cells the signal transduction of Y(5) NPY
      receptors is limited to inhibition of cAMP accumulation.

PMID- 11287094
TI  - Differential regulation of neuropeptide Y receptors in the brains of NPY knock
      out mice.
AB  - To study the effect of NPY deletion on the regulation of its receptors in the NPY
      knockout (NPY KO) mice, the expression and binding of NPY receptors were
      investigated by in situ hybridization and receptor autoradiography using (125)I
      [Leu(31),Pro(34)]PYY and (125)I-PYY(3-36) as radioligands. A 6-fold increase in
      Y2 receptor mRNA was observed in the CA1 region of the hippocampus in NPY KO
      mice, but a significant change could not be detected for Y1, Y4, Y5 and y6
      receptors. Receptor binding reveals a 60-400% increase of Y2 receptor binding in
      multiple brain areas. A similar increase in Y1 receptor binding was seen only in
      the hypothalamus. These results demonstrate the NPY receptor expression is
      altered in mice deficient for its natural ligand.

PMID- 11287095
TI  - Different binding sites for the neuropeptide Y Y1 antagonists 1229U91 and J
      104870 on human Y1 receptors.
AB  - The peptidic Y1 antagonist 1229U91 and the non-peptidic antagonist J-104870 have
      high binding affinities for the human Y1 receptor. These Y1 antagonists show
      anorexigenic effects on NPY-induced feeding in rats, although they have
      completely different structures and molecular sizes. To identify the binding
      sites of these ligands, we substituted amino acid residues of the human Y1
      receptor with alanine and examined the abilities of the mutant receptors to bind
      the radio-labeled ligands. Alanine substitutions, F98A, D104A, T125A, D200A,
      D205A, L215A, Q219A, L279A, F282A, F286A, W288A and H298A, in the human Y1
      receptor lost their affinity for the peptide agonist PYY, but not for 1229U91 and
      J-104870, while L303A and F173A lost affinity for 1229U91 and J-104870,
      respectively. N283A retained its affinity for 1229U91, but not for PYY and J
      104870. Y47A and N299A retained their affinity for J-104870, but not for PYY and
      1229U91. W163A and D287A showed no affinity for any of the three ligands. Taken
      together, these data indicate that the binding sites of 1229U91 are widely
      located in the shallow region of the transmembrane (TM) domain of the receptor,
      especially TM1, TM6 and TM7. In contrast, J-104870 recognized the pocket formed
      by TM4, TM5 and TM6, based on the molecular modeling of the Y1 receptor and J
      104870 complex. In conclusion, 1229U91 and J-104870 have high affinities for Y1
      receptors using basically different binding sites. D287 of the common binding
      site in the TM6 domain could be crucial for the binding of Y1 antagonists.

PMID- 11287096
TI  - Control of the expression of human neuropeptide Y by leptin: in vitro studies.
AB  - Neuropeptide Y (NPY) participates in the regulation of reproduction and food
      intake. The adipose-secreted hormone, leptin, has also been involved in these
      processes, and has been shown to exert its effects in part by controlling NPY
      synthesis and release at the hypothalamic level. In the present study, we
      utilized the SH-SY5Y human neuroblastoma cell line, to study the leptin-NPY
      interrelationships. SH-SY5Y cells were found to express leptin receptors (RT-PCR
      and Western blot analyses). A 24-h treatment with leptin at different
      concentrations did not affect NPY gene expression, but resulted in a stimulation
      of NPY release. This stimulated secretion was blocked by the combined treatment
      with leptin and the muscarinic agonist carbachol or the phorbol ester TPA. Leptin
      and carbachol also caused an increased intracellular content of NPY. In
      conclusion, the SH-SY5Y human neuroblastoma cell line appears to be a suitable in
      vitro model for studying the pharmacological effects of leptin on the
      biosynthesis and secretion of NPY.

PMID- 11287098
TI  - Neuropeptide Y and the adrenal gland: a review.
AB  - This paper sets out to review several aspects of NPY and adrenal function,
      starting with the localisation of NPY in the adrenal, then describing the
      regulation of NPY release and considering whether the adrenal is a significant
      source of circulating NPY. The review then describes the regulation of adrenal
      content of peptide, and finally covers the actions of NPY on the adrenal gland,
      and the receptor subtypes thought to mediate these effects. The regulation and
      actions of NPY are discussed with reference to both the adrenal cortex and the
      medulla.

PMID- 11287097
TI  - Increased insulin concentrations and glucose storage in neuropeptide Y Y1
      receptor-deficient mice.
AB  - Mice lacking NPY Y1 receptors develop obesity without hyperphagia indicating
      increased energy storage and/or decreased energy expenditure. Then, we
      investigated glucose utilization in these animals at the onset of obesity. Fasted
      NPY Y1 knockouts showed hyperinsulinemia associated with increased whole body and
      adipose tissue glucose utilization and glycogen synthesis but normal glycolysis.
      Since leptin modulates NPY actions, we studied whether the lack of NPY Y1
      receptor affected leptin-mediated regulation of glucose metabolism. Leptin
      infusion normalized hyperinsulinemia and glucose turnover. These results suggest
      a possible mechanism for the development of obesity without hyperphagia via
      dysfunction in regulatory loops involving NPY, leptin and insulin.

PMID- 11287099
TI  - ATP stimulated cyclic AMP formation in bovine chromaffin cells is enhanced by
      neuropeptide Y.
AB  - ATP increases cAMP formation in bovine chromaffin cells, EC(50) = 7.1 x 10(-6) M.
      NPY, EC(50) = 4.1 x 10(-8) M, increases the efficacy of ATP (1.5-2 fold).
      Inclusion of the selective Y1 receptor antagonist 1229U91 produced a decrease in
      NPY potency (EC(50) = 2.7 x 10(-7) M). PTX pretreatment did not abolish either
      the effect of ATP nor the enhancement by NPY. NPY could also enhance the ability
      of angiotensin and bradykinin to increase cAMP formation. The selective
      phospholipase C inhibitor, U73122, and the selective protein kinase C inhibitors,
      bisindolylmaleimide I and RO-31-8425, were effective inhibitors of the enhancing
      effect of NPY.

PMID- 11287100
TI  - Multiple Y receptors mediate pancreatic polypeptide responses in mouse colon
      mucosa.
AB  - A functional study has been performed to characterise the Y receptors responsible
      for NPY, PYY and PP-stimulated responses in mouse colonic mucosal preparations.
      Electrogenic ion secretion was stimulated with VIP following which NPY, PYY and
      PP analogues were, to varying degrees, inhibitory. PYY(3-36), hPP, Gln(23)hPP and
      rPP were effective but less potent than full length PYY, NPY or their Pro(34)
      substituted analogues, while the Y(5) agonist Ala(31), Aib(32)hNPY was the least
      active peptide tested. The Y(1) antagonists, BIBP3226 and BIBO3304 virtually
      abolished Pro(34)PYY and PYY responses while PYY(3-36) responses were selectively
      inhibited by the Y(2) antagonist, BIIE0246. A combination of BIBO3304 and
      BIIE0246 also partially attenuated hPP responses, leaving residual effects that
      were most probably Y(4)-mediated. Thus we conclude that Y(1), Y(2) and Y(4)
      receptors attenuate ion secretion in mouse colon.

PMID- 11287101
TI  - Critical role of dipeptidyl peptidase IV in neuropeptide Y-mediated endothelial
      cell migration in response to wounding.
AB  - Recently, we have discovered that neuropeptide Y (NPY), a sympathetic
      neurotransmitter, is also present in human umbilical endothelial cells (HUVECs),
      and is potently chemotactic and angiogenic by acting on one or several of Y1-Y5
      receptors. In HUVECs, NPY is co-localized with dipeptidyl peptidase IV (DPPIV)
      which cleaves Tyr(1)-Pro(2) from NPY(1-36) to form NPY(3-36) resulting in the
      formation of a non-Y1 receptor agonist, which remains angiogenic. Presently we
      studied the effects of DPPIV's blockade using monoclonal antibodies (mAbs) on
      migration of HUVECs in response to NPY(1-36) or NPY(3-36) following cell
      wounding. Both peptides caused similar dose-dependent increases in cell migration
      (+80% at 0.1 nM) 12 h after wounding. DPPIV mAbs, E19 and E26, significantly
      reduced HUVEC's migration below that of the untreated cells, and blocked
      responses to NPY(1-36) but not NPY(3-36). Enhanced expression of DPPIV was found
      in the migrating cells and in cells with their protrusions at the edge of the
      wound (immunostaining and Western blot). Thus, DPPIV's expression is stimulated
      by endothelial wounding and its enzymatic activity is required for NPY-mediated
      chemotaxis. Furthermore, this suggests that non-Y1 receptors activated by NPY(3
      36) (Y2, Y3 and/or Y5) mediate angiogenic effects of NPY.

PMID- 11287102
TI  - Decreased neuropeptide Y (NPY) expression in the infundibular nucleus of patients
      with nonthyroidal illness.
AB  - In patients with a variety of illnesses, serum concentrations of T3 decrease
      without giving rise to elevated serum levels of TSH, a phenomenon known as the
      sick euthyroid syndrome or nonthyroidal illness (NTI). Our previous studies in
      postmortem brain material showed decreased thyrotropin-releasing hormone (TRH)
      messenger RNA (mRNA) in the paraventricular nucleus (PVN) of patients with NTI,
      suggesting a role for TRH cells in the persistence of low TSH levels in NTI. In
      the present study, we hypothesized that changes in neuropeptide Y (NPY) input
      from the infundibular nucleus (IFN) to TRH cells in the PVN might be a
      determinant of decreased TRH expression in NTI. We investigated the hypothalamus
      of nine patients whose endocrine status had been assessed in a serum sample taken
      less than 24h before death and we examined NPY expression in the IFN by means of
      immunocytochemistry and mRNA in situ hybridization using an image analysis
      system. There was a negative correlation (r = -0.88; p = 0.01) between serum
      leptin concentrations and total NPY mRNA in the IFN. The total amount of NPY
      immunoreactivity in the IFN correlated with total NPY mRNA (r = 0.69; p = 0.04).
      In contrast to the situation in food-deprived rodents, total NPY immunoreactivity
      in the IFN showed a positive correlation with total TRH mRNA in the PVN (r =
      0.77; p = 0.02). The results suggest a role for decreased NPY input from the IFN
      in the resetting of thyroid hormone feedback on hypothalamic TRH cells in NTI.

PMID- 11287103
TI  - Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic
      axes in male rats are independent of adrenal hormones.
AB  - Neuropeptide Y (NPY) in the hypothalamus exerts multiple physiological functions
      including stimulation of adipogenic pathways such as feeding and insulin
      secretion as well as inhibition of the somatotropic and gonadotropic axes. Since
      hypothalamic NPY-ergic activity is increased by negative energy balance, NPY
      enables coordinated regulation of growth and reproduction in parallel with energy
      availability. Chronic pathological increases in central NPY-ergic activity
      contribute to obesity. Many of the adipogenic effects of NPY are specifically
      dependent on adrenal glucocorticoids. However, in the current study we show that
      central NPY does not require adrenal hormones to inhibit the somatotropic and
      gonadotropic axes in rats. Male adrenalectomized and sham-operated normal rats
      were intracerebroventricularly (ICV) infused with NPY (15 microg/day) or saline
      for 5-7 days, and plasma leptin, insulin-like growth factor (IGF-1) and
      testosterone were assayed, and epididymal white adipose tissue (WATe) was
      weighed. In normal intact rats, WATe weight and leptinemia were significantly
      increased by NPY, and these effects were prevented by adrenalectomy. In normal
      rats, NPY markedly reduced plasma IGF-1 levels (470 +/- 40 versus 1260 +/- 90
      ng/ml) and testosterone (0.53 +/- 0.28 versus 5.4 +/- 0.80 nmol/l in saline
      infused controls, p < 0.0001). Adrenalectomy decreased plasma IGF-1
      concentrations to 290 +/- 30 (p < 0.0001 versus normal rats), which were
      significantly reduced further by NPY. However, adrenalectomy had no significant
      effect on basal nor on NPY-induced plasma testosterone concentrations. In
      conclusion unlike the stimulatory effects of NPY on fat mass and leptinemia, NPY
      induced inhibition of the somatotropic and gonadotropic axes in male rats do not
      require adrenal hormones.

PMID- 11287104
TI  - A GABA-neuropeptide Y (NPY) interplay in LH release.
AB  - Neuropeptide Y (NPY) stimulates and gamma-amino butyric acid (GABA) inhibits LH
      release in the rat. Since a sub-population of NPY-producing neurons in the
      arcuate nucleus (ARC) of the hypothalamus co-express GABA, the possibility of an
      interplay between NPY and GABA in the release of LH was investigated in two ways.
      First by employing light and electron microscopic double staining for NPY and
      GABA, using pre and post-immunolabeling on rat brain sections, we detected GABA
      in NPY immunoreactive axon terminals in the MPOA, one of the primary sites of
      action of these neurotransmitters/neuromodulators in the regulation of LH
      release. These morphological findings raised the possibility that inhibitory GABA
      co-released with NPY may act to restrain the excitatory effects of NPY on LH
      release. Muscimol (MUS, 0.44 or 1.76 nmol/rat), a GABA(A) receptor agonist,
      administered intracerebroventricularly (icv), alone failed to affect LH release,
      but NPY (0.47 nmol/rat icv) alone stimulated LH release in ovarian steroid-primed
      ovariectomized rats. On the other hand, administration of MUS blocked the NPY
      induced stimulation of LH release in a dose-dependent manner. Similarly,
      administration of MUS abolished the excitatory effects on LH release of 1229U91,
      a selective NPY Y4 receptor agonist. These results support the possibility that
      in the event of co-release of these neurotransmitters/neuromodulators, GABA may
      act to restrain stimulation of LH release by NPY during the basal episodic and
      cyclic release of LH in vivo.

PMID- 11287105
TI  - Food intake inhibition and reduction in body weight gain in rats treated with
      GI264879A, a non-selective NPY-Y1 receptor antagonist.
AB  - Neuropeptide Y has been proposed to play a major role in the hypothalamic
      regulation of feeding behavior through the activation of specific, central NPY
      receptor(s). In an effort to design small molecule antagonists of NPY receptors,
      we have synthesized a series of substituted dipeptides based on defined
      pharmacophores, previously identified by us and others as essential for the
      interaction with the peptide receptors. GI264879A behaves as a functional
      antagonist of Y1 receptors while displaying no binding selectivity for the
      different NPY receptor subtypes. We demonstrate here that administration of
      GI264879A to rats causes a significant decrease in food intake and body weight
      partly through a mechanism dependent on the integrity of the vagus nerve.

PMID- 11287106
TI  - Feeding after fourth ventricular administration of neuropeptide Y receptor
      agonists in rats.
AB  - Neuropeptide Y (NPY) and peptide YY (PYY) stimulate food intake after injection
      into the fourth cerebral ventricle, suggesting that NPY receptors in the
      hindbrain are targets for the stimulatory effect of these peptides on food
      intake. However, the NPY/PYY receptor subtype mediating the feeding response in
      the hindbrain is not known. To approach to this question we compared dose-effect
      of several NPY receptor agonists to stimulate food intake in freely-feeding rats
      60- and 120-min after injection into the fourth cerebral ventricle. At the 120
      min time point, PYY was 2- to 10-times as potent as NPY over the dose-response
      range and stimulated twice the total intake at the maximally effective dose (2
      fold greater efficacy). NPY was 2-times as potent as the Y1, Y5 receptor agonist,
      [Leu(31)Pro(34)]NPY but acted with comparable efficacy. The Y5-, Y2
      differentiating receptor agonist, NPY 2-36, was comparable in potency to PYY at
      low doses but equal in efficacy NPY and [Leu(31)Pro(34)]NPY. The Y2 receptor
      agonist, NPY 13-36, produced only a marginal effect on total food intake. The
      profile of agonist potency after fourth cerebral ventricle administration is
      similar to the profile obtained when these or related agonists are injected in
      the region of the hypothalamus. Agonists at both Y1 and Y5 receptors stimulated
      food intake with a rank order of potency that does not conclusively favor the
      exclusive involvement of a single known NPY receptor subtype. Thus it is possible
      that the ingestive effects of NPY and PYY are mediated by multiple or novel
      receptor subtypes in the hindbrain. And the relatively greater potency and
      efficacy of PYY raises the possibility that a novel PYY-preferring receptor in
      the hindbrain is involved in the stimulation of food intake.

PMID- 11287107
TI  - Emerging functions of neuropeptide Y Y(2) receptors in the brain.
AB  - The Y(2) receptor is the predominant neuropeptide Y (NPY) receptor subtype in the
      brain. Y(2) receptor mRNA is discretely distributed in the brain, including
      specific subregions of the hippocampus and the hypothalamus, and is largely
      consistent with the distribution of Y(2) receptor protein demonstrated by
      radioligand-binding methods. Y(2) receptor-mediated effects have been reported
      principally based on the observations using the C-terminal fragments of NPY.
      Recent studies indicate an involvement of the receptor in food intake,
      gastrointestinal motility, cardiovascular regulation, and neuronal excitability.
      Very recently, Y(2) receptor selective antagonist has been developed and Y(2)
      receptor-deficient animals have been created. These new pharmacological tools
      will help to clarify the roles of this receptor in brain functions.

PMID- 11287108
TI  - The mPVN mediates blockade of NPY-induced feeding by a Y5 receptor antagonist: a
      c-FOS analysis.
AB  - To identify the site(s) of NPY Y5 receptor (Y5R) mediation of NPY-induced
      feeding, we employed c-Fos immunostaining and a selective Y5R antagonist (Y5R-A),
      CGP71683A, in adult male rats. Intracerebroventricular (icv) administration of
      NPY stimulated feeding and c-Fos-like immunoreactivity (FLI) in the dorsomedial
      hypothalamus, supraoptic nucleus and the two subdivision of the hypothalamic
      paraventricular nucleus (pPVN), the parvocellular (pPVN), and magnocellular
      (mPVN). Y5R-A on its own, injected either intraperitoneally or icv, neither
      affected feeding nor FLI in hypothalamic sites. However, Y5R-A pretreatment
      suppressed NPY-induced food intake and FLI selectively in the mPVN. Taken
      together with our previous similar finding of Y1R involvement, these results
      suggest that NPY receptor sites concerned with feeding behavior reside
      selectively in the mPVN and Y1 and Y5 receptors are either coexpressed or
      expressed separately in those target neurons that promote appetitive drive.

PMID- 11287109
TI  - Neuropeptide-Y in the paraventricular nucleus increases ethanol self
      administration.
AB  - The paraventricular nucleus (PVN) of the hypothalamus is known to modulate
      feeding, obesity, and ethanol intake. Neuropeptide-Y (NPY), which is released
      endogenously by neurons projecting from the arcuate nucleus to the PVN, is one of
      the most potent stimulants of feeding behavior known. The role of NPY in the PVN
      on ethanol self-administration is unknown. To address this issue, rats were
      trained to self-administer ethanol via a sucrose fading procedure and injector
      guide cannulae aimed at the PVN were surgically implanted. Microinjections of NPY
      and NPY antagonists in the PVN were conducted prior to ethanol self
      administration sessions. All doses of NPY significantly increased ethanol self
      administration and preference, and decreased water intake. The NPY antagonist D
      NPY partially reduced ethanol self-administration and completely blocked the
      effects of an intermediate dose of NPY (10 fmol) on ethanol intake, preference,
      and water intake. The competitive non-peptide Y1 receptor antagonist BIBP 3226
      did not significantly alter ethanol self-administration or water intake when
      administered alone in the PVN but it completely blocked the effect of NPY (10
      fmol) on ethanol intake. NPY infused in the PVN had no effect on ethanol self
      administration when tested in rats that did not have a long history of ethanol
      self-administration. The doses of NPY tested produced no effect on food intake or
      body weight measured during the 24-h period after infusion in either ethanol
      experienced or ethanol-inexperienced rats. These results indicate that elevation
      of NPY levels in the PVN potently increases ethanol self-administration and that
      this effect is mediated through NPY Y1 receptors.

PMID- 11287110
TI  - Repeated inhibitory effects of NPY on hippocampal CA3 seizures and wet dog
      shakes.
AB  - Intracerebroventricular injection of NPY inhibits epileptiform seizures and
      seizure-related "wet dog shakes" (WDS) following electrical stimulation of the
      dentate gyrus or subiculum. This study examined the effects of NPY on seizures
      and WDS elicited in hippocampal CA3. Like in the other hippocampal regions, NPY
      significantly inhibited both seizures and accompanying WDS consistent with in
      vitro data. The identification of an additional antiepileptic hippocampal target
      for NPY could prove therapeutically relevant considering that the hippocampal
      formation is a frequent seizure focus in human epilepsy. The effects of NPY were
      found to persist on seven repeated NPY injection days. Thus tolerance to the anti
      seizure effects of NPY does not appear to develop rapidly. Tolerance being a
      problem with several current antiepileptic drugs, this further strengthens the
      concept of NPY receptors as a potential future antiepileptic target.

PMID- 11287111
TI  - Neuropeptide Y and epilepsy: varying effects according to seizure type and
      receptor activation.
AB  - In vitro and in vivo experiments suggest antiepileptic properties for NPY. In
      this study, the pharmacology of these effects was examined and compared in
      different rat models of seizures. Agonists for Y(1), Y(2) and Y(5) receptors
      reduced seizure-like activity in hippocampal cultures. Intracerebral injection of
      NPY or Y(5) agonists reduced the expression of focal seizures produced by a
      single electrical stimulation of the hippocampus. Conversely, NPY agonists
      increased the duration of generalized convulsive seizures induced by
      pentylenetetrazol. These results suggest that NPY reduces seizures of hippocampal
      origin through activation of Y(5) receptors. They also point to probable
      modulatory effects of NPY in brain structures other than the hippocampus,
      involved in initiation, propagation or control of seizures.

PMID- 11287112
TI  - Does neuropeptide Y contribute to the anorectic action of amylin?
AB  - Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the
      hypothalamus. Amylin, a peptide co-released with insulin from pancreatic beta
      cells, inhibits feeding following peripheral or central administration. However,
      the mechanism by which amylin exerts its anorectic effect is controversial. This
      study investigated the acute effect of amylin on food intake induced by NPY, and
      the effect of chronic amylin administration on food intake and body weight in
      male Sprague Dawley rats previously implanted with intracerebroventricular (icv)
      cannulae. Rats received 1 nmol NPY, followed by amylin (0.05, 0.1, 0.5 nmol) or 2
      microl saline. Increasing doses of amylin resulted in a dose-dependent inhibition
      of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine
      the chronic effects of i.c.v. amylin administration on feeding, rats received 0.5
      nmol amylin or saline daily, 30 min before dark phase, over 6 days. Amylin
      significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days, amylin
      treated rats showed a significant reduction in body weight, having lost 17.3 +/-
      6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY
      concentrations were not elevated, despite the reduced food intake, suggesting
      amylin may regulate NPY production or release. Thus, amylin potently inhibits NPY
      induced feeding and attenuates normal 24 hour food intake, leading to weight
      loss.

PMID- 11287113
TI  - Neuropeptide Y in the mammalian circadian system: effects on light-induced
      circadian responses.
AB  - The present review examine the role of neuropeptide (NPY) in the circadian
      system, focusing on the interactions between light and NPY, especially during the
      subjective night. NPY has two different effects on the circadian system of
      mammals. On one hand, NPY, similar to behavioral stimulation, can change the
      phase of the clock by itself during the subjective day. On the other hand, NPY,
      again similar to behavioral stimulation, can inhibit the phase-shifting effect of
      light during the night. These effects of NPY may occur through different receptor
      subtypes, the Y2 receptor mediating day-time effects and the Y5 receptor
      mediating night-time effects of NPY. Our results also indicate that there are
      differences between in vivo and in vitro studies: NPY inhibition of in vivo light
      induced phase shifts was observed only late in the subjective night; however, NPY
      applied in vitro could block light-induced phase shifts early in the subjective
      night as well. Contrasting these in vivo and in vitro results led us to suggest
      that the time of day of maximal effect of NPY in the intact animal may be a time
      when exogenous administration of NPY has little effect, due to saturation of the
      system. This situation could be an example of how the measurable output of the
      clock can be affected by the behavioral state in a different way at different
      time points, depending not only on the clock itself but also on behavior. If
      verified in human beings, the ability of NPY to modulate the circadian-clock
      responses to light may be of clinical importance.

PMID- 11287114
TI  - Occurrence of ovalbumin in ovarian yolk of chicken during oogenesis.
AB  - Yolk specimens from chicken ovaries during oogenesis gave a positive signal for
      ovalbumin as analyzed by Western blotting, indicating that the ovarian yolk
      contains ovalbumin. Northern blotting and reverse transcriptase-polymerase chain
      reaction gave a negative signal for ovalbumin mRNA in the liver and other organs
      except oviduct, whereas the laying hen serum was found to indicate
      immunologically the presence of ovalbumin. It was therefore assumed that
      ovalbumin synthesized in the oviduct might partly be secreted into the blood
      circular system, from which it is taken up into the oocyte.

PMID- 11287115
TI  - A rapid and sensitive method for the analysis of cyanophycin.
AB  - A method has been devised for the quantitative analysis of cyanophycin, based on
      (1)H nuclear magnetic resonance (NMR) spectroscopy, allowing determination of the
      nitrogen status of cyanobacteria. Cyanophycin is extracted with minimal washing
      from small volumes of cells and quantified by integration of the NMR peak
      attributed to the protons attached to the delta-carbon of arginine. Linear
      relationships were found between the amount of cyanophycin determined by this
      method and both known concentrations of cyanophycin solutions and the amount of
      cyanophycin determined using the standard chemical arginine assay.

PMID- 11287116
TI  - Oxidative stress increases MICA and MICB gene expression in the human colon
      carcinoma cell line (CaCo-2).
AB  - The human major histocompatibility complex class I chain-related A gene (MICA)
      and the MICB gene are newly identified members of the major histocompatibility
      complex class I chain-related gene family. We demonstrate here that oxidative
      stress, induced by H(2)O(2), promoted MICA (2.2-fold) and MICB (3.8-fold) gene
      expression using the human colon carcinoma cell line (CaCo-2) and semi
      quantitative RT-PCR.

PMID- 11287117
TI  - Heme oxygenase-1 induction by nitric oxide in RAW 264.7 macrophages is
      upregulated by a cyclo-oxygenase-2 inhibitor.
AB  - Unstimulated RAW 264.7 macrophages express negligible heme oxygenase-1 (HO-1)
      protein but incubation with the nitric oxide (NO) donor spermine nonoate (SPNO)
      induced HO-1 and weakly cyclo-oxygenase-2 (COX-2) protein. This effect was
      potentiated by coincubation with the COX-2 selective inhibitor, SC58125. Cells
      incubated with SPNO showed a strong increase in HO-1 mRNA levels after 4 h with a
      significant potentiation in the presence of SC58125, which did not modify HO-1
      mRNA stability. The induction of HO-1 by NO and its potentiation by anti
      inflammatory agents may play a role in inflammatory and immune responses.

PMID- 11287118
TI  - Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a
      potential role in body weight control.
AB  - Interleukin (IL)-15 is a cytokine which is highly expressed in skeletal muscle.
      Cell culture studies have indicated that IL-15 may have an important role in
      muscle fiber growth and anabolism. However, data concerning the metabolic effects
      of this cytokine in vivo are lacking. In the present study, IL-15 was
      administered to adult rats for 7 days. While IL-15 did not cause changes in
      either muscle mass or muscle protein content, it induced significant changes in
      the fractional rates of both muscle protein synthesis and degradation, with no
      net changes in protein accumulation. Additionally, IL-15 administration resulted
      in a 33% decrease in white adipose tissue mass and a 20% decrease in circulating
      triacylglycerols; this was associated with a 47% lower hepatic lipogenic rate and
      a 36% lower plasma VLDL triacylglycerol content. The decrease in white fat
      induced by IL-15 was in adipose tissue. No changes were observed in the rate of
      lipolysis as a result of cytokine administration. These findings indicate that IL
      15 has significant effects on both protein and lipid metabolism, and suggest that
      this cytokine may participate in reciprocal regulation of muscle and adipose
      tissue mass.

PMID- 11287119
TI  - Three mutations in v-Rel render it resistant to cleavage by cell-death protease
      caspase-3.
AB  - The retroviral oncoprotein v-Rel is a transcriptional activator in the Rel/NF
      kappa B family. v-Rel causes rapidly fatal lymphomas in young chickens, and
      transforms and immortalizes chicken lymphoid cells in vitro. Several mutations
      that have enhanced the oncogenicity of v-Rel have been selected during in vitro
      and in vivo passage of v-Rel-containing retroviruses. In this report, we show
      that the C-terminal deletion and two point mutations (Asp-->Gly at residue 91 and
      Asp-->Asn at residue 437) in v-Rel make it resistant to cleavage by the cell
      death protease caspase-3. In contrast, c-Rel, which has Asp residues at these
      sites, can be cleaved by caspase-3 in vitro as well as in vivo in cells induced
      to undergo apoptosis. We have characterized activities of v-Rel mutants with
      recreated single caspase-3 cleavage sites, two cleavage sites, or an introduced
      artificial cleavage site. All of these mutant v-Rel proteins are sensitive to
      caspase-3 cleavage in vitro, and show wild-type activity in terms of nuclear
      localization in chicken fibroblasts and DNA binding in vitro. Moreover, all
      caspase-3-sensitive v-Rel mutants transform chicken spleen cells in vitro and
      induce fatal lymphoid tumors in vivo to approximately the same extent as wild
      type v-Rel. As with v-Rel mutants, caspase-3-resistant c-Rel mutants behave
      similarly to caspase-3-sensitive wild-type c-Rel in terms of DNA binding,
      transcriptional activation, in vitro transformation, and tumorigenicity.
      Mammalian c-Rel proteins can also be cleaved by caspase-3 in vitro, and a c-Rel
      mutant from a human pre-T lymphoma cell line is less sensitive than wild-type
      human c-Rel to cleavage by caspase-3. Taken together, these results demonstrate
      that specific mutations render oncogenic forms of Rel proteins resistant to
      cleavage by a cell-death caspase; however, the biological relevance of this
      resistance remains unclear. Nevertheless, to our knowledge, this is the first
      demonstration of mutations in caspase-3 recognition sites occurring during the
      evolution of an oncogenic protein.

PMID- 11287120
TI  - Screening of a unique lectin from 16 cultivable mushrooms with hybrid
      glycoprotein and neoproteoglycan probes and purification of a novel N
      acetylglucosamine-specific lectin from Oudemansiella platyphylla fruiting body.
AB  - Hybrid glycoprotein and neoproteoglycan probes were prepared by coupling various
      glycoproteins or polysaccharides to peroxidase or biotinyl bovine serum albumin,
      respectively. Lectins recognizable by the neoglycoconjugate probes were extracted
      from 16 cultivable mushrooms. Dot-blot assay revealed five extracts to be
      reactive with only hybrid glycoprotein probes, but others also reacted with
      neoproteoglycan probes. According to the reactivity pattern with probe screening,
      the one lectin from Oudemansiella platyphylla extract (OPL) bound best with
      asialotransferrin-- and asialoagalactotransferrin--peroxidase probes and was
      isolated using an asialotransferrin column, but it did not bind with other hybrid
      glycoprotein or neoproteoglycan probes. OPL, consisting of two polypeptides with
      high homology in the N-terminal amino acid sequences, exhibited weak
      hemagglutinating activity. Purified OPL specifically bound the beta-GlcNAc probe
      among various biotinylated polymeric sugar probes, while it exhibited essentially
      the same binding specificity toward neoglycoconjugate probes as that of the crude
      extract, showing a preference for the asialobiantennary complex type of N-linked
      glycans. These results indicate that the neoglycoconjugate probes are valuable in
      lectin screening.

PMID- 11287121
TI  - Metabolism and effects on cholestasis of isoursodeoxycholic and ursodeoxycholic
      acids in bile duct ligated rats.
AB  - Isoursodeoxycholic acid (isoUDCA), the 3 beta-epimer of ursodeoxycholic acid
      (UDCA), may have pharmaceutical potential because of its similar hydrophilicity
      and in vitro cytoprotection as compared with UDCA. We compared metabolism and
      effects on cholestasis of UDCA and isoUDCA in experimental cholestasis in rats.
      Cholestasis was induced by bile duct ligation. For bile flow and biliary bile
      acid analysis, UDCA or isoUDCA were infused intraduodenally. For the study of
      chronic effects, chow was supplemented with 2.5 g/kg UDCA or isoUDCA for 3 weeks.
      Sham-operated animals served as controls. IsoUDCA became completely converted to
      UDCA in the liver. Choleresis and biliary bile acids were the same after the
      intraduodenal administration of either compound. Oral administration of UDCA or
      isoUDCA significantly improved liver biochemistry but not clinical and
      histological parameters in chronic cholestasis. The decrease of serum cholic acid
      in control animals was more pronounced after isoUDCA (-93%) than after UDCA (
      76%). Only after UDCA, this decrease was compensated by increases of UDCA, beta
      muricholic acid (MCA), and Delta(22)-beta-MCA. Our results show that isoUDCA has
      the same effect on choleresis and liver biochemistry as UDCA. IsoUDCA features
      pro-drug characteristics of UDCA and causes compared to the latter lower serum
      bile acid concentrations in non-cholestatic animals.

PMID- 11287122
TI  - Effect of albumin on the kinetics of ascorbate oxidation.
AB  - The fluorescence intensity of the fluorophore in dansyl piperidine-nitroxide is
      intramolecularly quenched by the nitroxyl fragment. Therefore, the oxidation of
      ascorbic acid by the fluorophore-nitroxide (FN) probe can be monitored by two
      independent methods: steady-state fluorescence and electron paramagnetic
      resonance. Bovine serum albumin (BSA) affects the rate of this reaction. The
      influence of BSA on the rate is attributed to the adsorption of both ascorbate
      and the probe to BSA. Adsorption of ascorbate to BSA is confirmed by NMR
      relaxation experiments. The spatial distribution of the molecules on the BSA
      surface changes the availability of ascorbate and FN to each other. The results
      also point out that, in the presence of BSA, the autoxidation of ascorbate is
      significantly slowed down. The effect is studied at different pH values and
      explained in terms of the electrostatic interaction between the ascorbate anion
      and the BSA molecule.

PMID- 11287123
TI  - Adsorption of IgG onto hydrophobic teflon. Differences between the F(ab) and F(c)
      domains.
AB  - The effect of differences in the degree of hydrophobicity of protein
      patches/fragments on the adsorption behaviour of the protein is investigated. The
      adsorption isotherm of a monoclonal mouse anti-human immunoglobulin G (isotype
      2b) onto hydrophobic Teflon particles is measured using a depletion method. The
      adsorption-induced denaturation of the immunoglobulin as a function of the
      adsorbed amount is studied by differential scanning calorimetry, and the
      corresponding rearrangements in the secondary structure of the whole IgG molecule
      and its F(ab) and F(c) fragments are determined by circular dichroism
      spectroscopy. The effects of adsorption on the F(ab) and F(c) fragments in the
      intact IgG molecule occur independently. Adsorption of the whole IgG molecule
      leads to denaturation of the F(ab) fragments, whereas the F(c) fragment remains
      unperturbed; adsorption of the isolated fragments results in structural changes
      in both F(ab) and F(c). The surface hydrophobicity of the isolated fragments was
      studied by HPLC. These experiments support the hypothesis that differences in the
      degree of denaturation between F(ab) and F(c) are due to the higher degree of
      hydrophobicity of the F(ab) fragment. The adsorption-induced changes in the
      secondary structure are more prominent for the isolated fragments as compared to
      intact IgG. This is ascribed to the higher flexibility of the isolated fragment,
      as compared to the fragment in the whole molecule.

PMID- 11287124
TI  - UDP hydrolase activity associated with the porcine liver annexin fraction.
AB  - In the crude fraction of porcine liver annexins, we identified annexin IV
      (AnxIV), AnxII and AnxVI of MW (molecular weight) of 32, 36 and 68 kDa,
      respectively, an albumin of MW of 61.5 kDa and an UDP hydrolase (UDPase) of MW of
      62 kDa, related to the human UDPase from Golgi membranes. The latter enzyme
      exhibits its highest specificity towards UDP and GDP but not ADP and CDP, and it
      is stimulated by Mg(2+) and Ca(2+). AnxVI itself, although it binds purine
      nucleotides, does not exhibit hydrolytic activity towards nucleotides. Taken
      together, these results suggest that AnxVI may interact in vivo with a nucleotide
      utilizing enzyme, UDPase. This is in line with observations made by other
      investigators that various annexins are able to interact with nucleotide
      utilizing proteins, such as protein kinases, GTPases, cytoskeletal proteins and
      p120(GAP). Such interactions could be of particular importance in modulating the
      biological activities of these proteins in vivo.

PMID- 11287125
TI  - Developmental expression and distribution of amphibian glutathione transferases.
AB  - This work is aimed at detecting the expression and location of embryonic Bufo
      bufo GST (bbGSTP1-1) and adult B. bufo GST (bbGSTP2-2) during toad development,
      in order to assign a putative role to these enzymes also on the basis of their
      compartmentalization and to verify whether during the premetamorphic liver
      ontogeny the bbGSTP2-2 form appears. This study was also performed in the adult
      liver (the primary site of Pi class GST expression) and in the mature ovary, to
      discern if the embryonic form derives from maternal form. The results show that
      the embryos and the ovary express only bbGSTP1-1. Moreover, bbGSTP1-1
      distribution is the same both in the early embryos and in the ovary: this
      strongly suggests that bbGSTP1-1 is of maternal origin. As development goes on, a
      wide distribution of bbGSTP1-1 all over the differentiating organs is observed.
      The embryonic liver expresses exclusively the bbGSTP1-1 form, while the adult
      liver is highly positive only towards the bbGSTP2-2 form. This implies that the
      switch towards the adult bbGSTP2-2 form occurs in metamorphic or postmetamorphic
      phases and that the detoxication metabolic requirements of the embryo may be
      completely fulfilled by the bbGSTP1-1 isoenzyme.

PMID- 11287126
TI  - Human placenta hydrolases active on free ADP-ribose: an ADP-sugar pyrophosphatase
      and a specific ADP-ribose pyrophosphatase.
AB  - Free ADP-ribose has a reducing ribose moiety and it is hazardous due to its
      nonenzymic reactivity toward protein side chains. ADP-ribose hydrolases are
      putative protective agents to avoid the intracellular accumulation of ADP-ribose.
      In mammalian sources, two types of enzymes with ADP-ribose hydrolase activity are
      known: (i) highly specific ADP-ribose pyrophosphatases, which in a Mg(2+)
      dependent fashion hydrolyse only ADP-ribose and the nonphysiological analogue IDP
      ribose, and (ii) less specific nucleoside diphosphosugar or diphosphoalcohol (NDP
      X) pyrophosphatases, which besides A(I)DP-ribose hydrolyse also some nonreducing
      NDP-X substrates. So far, of these two enzyme types only the less specific one
      has been reported in human sources: an ADP-sugar pyrophosphatase purified from
      erythrocytes or expressed from cDNA clones. Here we report that human placenta
      extracts contain two ADP-ribose hydrolases, which were characterised after a near
      1000-fold purification. One is an ADP-sugar pyrophosphatase: it hydrolysed ADP
      ribose, ADP-glucose and ADP-mannose, but not e.g. UDP-glucose, at similar rates.
      It resembles the erythrocyte and recombinant enzyme(s), but showed a 5-20-fold
      lower K(m) for ADP-ribose (7 microM). The other enzyme is a highly specific ADP
      ribose pyrophosphatase (the first of this kind to be reported in humans): it
      hydrolysed only ADP-ribose and IDP-ribose at similar rates, with a very low, 0.4
      microM K(m) for the former. This is a major candidate to control the accumulation
      of free ADP-ribose in humans. It remains to be seen whether it belongs to the
      'nudix' protein family, which includes several ADP-ribose hydrolases and other
      'housecleaning' enzymes (M.J. Bessman, D.N. Frick, S.F. O'Handley, J. Biol. Chem.
      271 (1996) 25059-25062).

PMID- 11287127
TI  - Involvement of the perferryl complex of nitric oxide synthase in the catalysis of
      secondary free radical formation.
AB  - Neuronal nitric oxide synthase (NOS I) has been shown to generate nitric oxide
      (NO*) and superoxide (O(2)* during enzymatic cycling, and the ratio of each free
      radical is dependent upon the concentration of L-arginine. Using spin trapping
      and electron paramagnetic resonance spectroscopy, we detected alpha-hydroxyethyl
      radical (CH(3)*CHOH), produced during the NOS I metabolism of ethanol (EtOH). The
      generation of CH(3)*CHOH by NOS I was found to be Ca(2+)/calmodulin dependent.
      Superoxide dismutase prevented CH(3)*CHOH formation in the absence of L-arginine.
      However, in the presence of L-arginine, the production of CH(3)*CHOH was
      independent of O(2)* but dependent upon the concentration of L-arginine.
      Formation of CH(3)*CHOH was inhibited by substituting D-arginine for L-arginine,
      or inclusion of the NOS inhibitors N(G)-nitro-L-arginine methyl ester, N(G)
      monomethyl-L-arginine and the heme blocker, sodium cyanide. The addition of
      potassium hydrogen persulfate to NOS I, generating the perferryl complex (NOS
      [Fe(5+)=O](3+)) in the absence of oxygen and Ca(2+)/calmodulin, and EtOH resulted
      in the formation of CH(3)*CHOH. NOS I was found to produce the corresponding
      alpha-hydroxyalkyl radical from 1-propanol and 2-propanol, but not from 2-methyl
      2-propanol. Data demonstrated that the perferryl complex of NOS I in the presence
      of L-arginine was responsible for catalyses of these secondary reactions.

PMID- 11287128
TI  - Antithrombin binding of low molecular weight heparins and inhibition of factor
      Xa.
AB  - Fluorescence and stopped flow methods were used to compare clinically used
      heparins with regard to their ability to bind to antithrombin and to accelerate
      the inactivation of factor Xa. Titration of antithrombin with both low molecular
      weight heparin (LMWH) (enoxaparin, fragmin and ardeparin) and unfractionated
      heparin (UFH) produced an equivalent fluorescence increase and indicates similar
      affinity of all heparin preparations to antithrombin. However, relative to UFH
      enoxaparin, the LMWH with the smallest average molecular mass, contained only 12%
      material with high affinity for antithrombin. The rate of factor Xa inhibition by
      antithrombin increased with the concentration of the examined heparins to the
      same limiting value, but the concentration required for maximal acceleration
      depended on the preparation. According to these data the high affinity fraction
      of the heparin preparations increased the intrinsic fluorescence and inhibitory
      activity equally without additional effects by variations in chain length and
      chemical composition. In contrast, in the presence of Ca UFH accelerated the
      inhibition of factor Xa by antithrombin 10-fold more efficiently than comparable
      concentrations of the high affinity fractions of enoxaparin and fragmin. The bell
      shaped dependence of this accelerating effect suggests simultaneous binding of
      both proteins to heparin. In conclusion, under physiologic conditions the anti
      factor Xa activity of heparin results from a composite effect of chain length and
      the content of material with high affinity to antithrombin. Thus, the reduced
      antithrombotic activity of LMWH relative to UFH results from a smaller content of
      high affinity material and the absence of a stimulating effect of calcium.

PMID- 11287129
TI  - The dynamics of cortical macronetworks in the human brain: introduction and
      overview.

PMID- 11287130
TI  - Maturation of white matter in the human brain: a review of magnetic resonance
      studies.
AB  - This review focuses on the maturation of brain white-matter, as revealed by
      magnetic resonance (MR) imaging carried out in healthy subjects. The review
      begins with a brief description of the nature of the MR signal and its possible
      biological underpinnings, and proceeds with a description of MR findings obtained
      in newborns, infants, children and adolescents. On MR images, a significant
      decrease in water content leads to a decrease of longitudinal relaxation times
      (T1) and transverse relaxation times (T2) and consequent "adult-like" appearance
      of T1-weighted and T2-weighted images becomes evident towards the end of the
      first year of life. Owing to the onset of myelination and the related increase of
      lipid content, MR images gradually acquire an exquisite grey-white matter
      contrast in a temporal sequence reflecting the time course of myelination. Albeit
      less pronounced, age-related changes in white matter continue during childhood
      and adolescence; white matter increases its overall volume and becomes more
      myelinated in a region-specific fashion. Detection of more subtle changes during
      this "late" phase of brain development is greatly aided by computational analyses
      of MR images. The review also briefly outlines future directions, including the
      use of novel MR techniques such as diffusion tensor imaging and magnetization
      transfer, as well as the suggestion for the concurrent use of experimental
      behavioral test-batteries, with structural MR imaging, to study developmental
      changes in structure-function relationships.

PMID- 11287131
TI  - Interpreting PET and fMRI measures of functional neural activity: the effects of
      synaptic inhibition on cortical activation in human imaging studies.
AB  - Human brain imaging methods such as postiron emission tomography and functional
      magnetic resonance imaging have recently achieved widespread use in the study of
      both normal cognitive processes and neurological disorders. While many of these
      studies have begun to yield important insights into human brain function, the
      relationship between these measurements and the underlying neuronal activity is
      still not well understood. One open question is how neuronal inhibition is
      reflected in these imaging results. In this paper, we describe how large-scale
      modeling can be used to address this question. Specifically, we identify three
      factors that may play a role in how inhibition affects imaging results: (1) local
      connectivity; (2) context; and (3) type of inhibitory connection. Simulation
      results are presented that show how the interaction among these three factors can
      explain seemingly contradictory experimental results. The modeling suggests that
      neuronal inhibition can raise brain imaging measures if there is either low local
      excitatory recurrence or if the region is not otherwise being driven by
      excitation. Conversely, with high recurrence or actively driven excitation,
      inhibition can lower observed values.

PMID- 11287132
TI  - Dynamic representations and generative models of brain function.
AB  - The main point made in this article is that the representational capacity and
      inherent function of any neuron, neuronal population or cortical area is dynamic
      and context-sensitive. This adaptive and contextual specialisation is mediated by
      functional integration or interactions among brain systems with a special
      emphasis on backwards or top-down connections. The critical notion is that
      neuronal responses, in any given cortical area, can represent different things at
      different times. Our argument is developed under the perspective of generative
      models of functional brain architectures, where higher-level systems provide a
      prediction of the inputs to lower-level regions. Conflict between the two is
      resolved by changes in the higher-level representations, driven by the resulting
      error in lower regions, until the mismatch is 'cancelled'. In this model the
      specialisation of any region is determined both by bottom-up driving inputs and
      by top-down predictions. Specialisation is therefore not an intrinsic property of
      any region but depends on both forward and backward connections with other areas.
      Because these other areas have access to the context in which the inputs are
      generated they are in a position to modulate the selectivity or specialisation of
      lower areas. The implications for 'classical' models (e.g., classical receptive
      fields in electrophysiology, classical specialisation in neuroimaging and
      connectionism in cognitive models) are severe and suggest these models provide
      incomplete accounts of real brain architectures. Generative models represent a
      far more plausible framework for understanding selective neurophysiological
      responses and how representations are constructed in the brain.

PMID- 11287133
TI  - Cortical networks for working memory and executive functions sustain the
      conscious resting state in man.
AB  - The cortical anatomy of the conscious resting state (REST) was investigated using
      a meta-analysis of nine positron emission tomography (PET) activation protocols
      that dealt with different cognitive tasks but shared REST as a common control
      state. During REST, subjects were in darkness and silence, and were instructed to
      relax, refrain from moving, and avoid systematic thoughts. Each protocol
      contrasted REST to a different cognitive task consisting either of language,
      mental imagery, mental calculation, reasoning, finger movement, or spatial
      working memory, using either auditory, visual or no stimulus delivery, and
      requiring either vocal, motor or no output. A total of 63 subjects and 370
      spatially normalized PET scans were entered in the meta-analysis. Conjunction
      analysis revealed a network of brain areas jointly activated during conscious
      REST as compared to the nine cognitive tasks, including the bilateral angular
      gyrus, the left anterior precuneus and posterior cingulate cortex, the left
      medial frontal and anterior cingulate cortex, the left superior and medial
      frontal sulcus, and the left inferior frontal cortex. These results suggest that
      brain activity during conscious REST is sustained by a large scale network of
      heteromodal associative parietal and frontal cortical areas, that can be further
      hierarchically organized in an episodic working memory parieto-frontal network,
      driven in part by emotions, working under the supervision of an executive left
      prefrontal network.

PMID- 11287134
TI  - Cerebral networks in sensorimotor disturbances.
AB  - Increasing evidence suggests that the human brain employs multiple,
      interconnected brain areas for information processing and control of behavior,
      including the performance of laboratory tasks. Brain diseases are expected to
      affect these networks directly by interference and indirectly as a consequence of
      deficit compensation. Covariance analyses applied to functional brain imaging
      data open the opportunity to study neural networks and their disease-related
      changes in the human brain. Here, we review our analytic approach based on
      principal component analysis (PCA) to address such questions. We will discuss its
      methodological foundations and applications in patients with sensorimotor
      disorders. We will show that PCA in combination with, both, hypothesis-driven
      testing and correlation statistics provides a powerful tool for elucidating
      disease-related abnormalities and postlesional reorganization of neural networks
      in the human brain.

PMID- 11287135
TI  - Processing of odorous signals in humans.
AB  - from the first contact of an odor molecule with a receptor in the olfactory
      epithelium, to the coding and processing of this information in the central
      nervous system, the arousal of feelings and the storage of memories. The present
      chapter gives a short overview over the major components of these processes in
      humans.

PMID- 11287136
TI  - Different neural systems for recognizing plants, animals, and artifacts.
AB  - The purpose of this study was to investigate functional organization in the human
      brain involved in the representation of knowledge regarding plants. We measured
      the brain activity of eight male volunteers during the recognition of visual
      stimuli representing plants, animals and artifacts, using positron emission
      tomography. The participants were presented with and were required to name
      silently two different images each of 15 entities belonging to three ontological
      categories, and 30 series of four to six digits. Marked increases in regional
      cerebral blood flow were found in the hippocampus and the parahippocampal areas
      bilaterally and the right lateral occipital cortex during the silent naming of
      all three categories, compared with that during the silent reading of digits. The
      right lateral occipital cortex was specifically activated in association with the
      naming of plants, and the right fusiform cortex was specifically activated in
      association with the naming of animals. In addition, the right temporo-occipital
      cortex was activated only during animals and plants, not artifacts. Our results
      indicate that there were a few characteristic activations for the different
      categories, and that entities belonging to the different categories are not
      necessarily represented in different locations of the brain.

PMID- 11287137
TI  - Neural networks for internal reading and visual imagery of reading: a PET study.
AB  - Regional cerebral blood flow (rCBF) measurements with positron emission
      tomography (PET) were made on 10 volunteers in rest condition as well as while
      the subjects, with closed eyes, (i) internally listed the letters of the alphabet
      and cited the first verse of the Hungarian national anthem, (ii) visualised the
      capital letters of the alphabet, and (iii) visualised the capital letters of the
      first verse of the Hungarian national anthem. Significant changes in rCBF
      indicated various networks of cortical neuronal populations active during the
      tasks. Internal listing, as compared to the rest condition, activated the left
      precentral gyrus. Visualising the letters of the alphabet, when compared to the
      rest condition, activated a cortical network comprising fields along the banks of
      the left and right intraparietal sulci, the left medial frontal, precentral and
      occipital sulci, and the right superior frontal gyrus. Visualising the letters of
      the anthem, when compared to the rest condition, activated a cortical network
      comprising fields along the banks of the left and right intraparietal sulci, the
      left medial and inferior frontal gyri, and the right anterior cingulate gyrus.
      Contrasting the two visualisation tasks revealed task specific activation in the
      left lateral occipital gyrus (alphabet vs. anthem visualisation) and in the left
      anterior cingulate gyrus (anthem vs. alphabet visualisation). The data indicate
      that visual imagery of letters of the alphabet or a text engages a widespread
      network of cortical fields in the visual association cortices and the frontal
      cortex, without the engagement of the primary (V1) and secondary (V2) visual
      cortical areas. This finding supports the hypothesis that neuronal populations
      engaged by visual imagery and visual perception only partially overlap. The
      networks, activated in the visualisation tasks, have a core which is identical in
      the different visualisation tasks. The core network is complemented in a task
      specific manner by the recruitment of additional cortical neuronal populations.

PMID- 11287138
TI  - Chlamydia pneumoniae and atherosclerosis: does the evidence support a causal or
      contributory role?
AB  - The intracellular bacterial pathogen Chlamydia pneumoniae causes respiratory
      tract infection and has been associated with atherosclerosis and coronary artery
      disease. Since atherosclerosis is a progressive disease and is considered to be a
      chronic inflammation of the artery vessel wall, the interaction of C. pneumoniae
      with cells of the vasculature that can result in a local inflammatory response is
      of paramount importance. In this essay we review the pathophysiology of
      atherosclerosis in the context of C. pneumoniae infection and present an
      integrated model that includes the involvement of C. pneumoniae in all stages of
      atherogenesis including initiation, inflammation, fibrous plaque formation,
      plaque rupture and thrombosis. We hypothesize that acute and persistent infection
      of professional immune cells (T-cells, monocytes and macrophages) and non-immune
      cells (endothelial cells and smooth muscle cells) contributes to a sustained
      inflammatory response mediated by extensive cellular 'crosstalk' and numerous
      cytokines/chemokines. This cascade of inflammatory mediators may contribute to
      cellular dysfunction and tissue remodelling of the arterial intima. An improved
      understanding of the precise mechanism(s) of C. pneumoniae involvement in
      atherogenesis may help resolve the question of causality however, at the present
      time, we interpret the data as favoring a contributory rather than a causal role.
      Future research directed at the discovery of chlamydial virulence factors
      necessary for intracellular survival and subsequent alterations in host cell gene
      expression including signalling pathways may be important for the design of
      future clinical trials.

PMID- 11287139
TI  - Cytotoxic T cells and mycobacteria.
AB  - How the immune system kills Mycobacterium tuberculosis is still a puzzle. The
      classical picture of killing due to phagocytosis by activated macrophages may be
      only partly correct. Based on recent evidence, we express here the view that
      cytotoxic T lymphocytes also make an important contribution and suggest that DNA
      vaccines might be a good way to enhance this.

PMID- 11287140
TI  - tRNA genes were found in Piscirickettsia salmonis 16S-23S rDNA spacer region
      (ITS).
AB  - Piscirickettsia salmonis is the etiological agent of Salmonid Rickettsial
      Septicemia, a disease affecting salmon aquaculture industry. We analyzed the 16S
      23S rDNA spacer region (internal transcribed spacer, ITS) of Chilean P. salmonis
      isolates LF-89 and EM-90. Two main ITS amplification products were obtained by
      PCR using L1 and G1 primers, differing from that described where only one ITS
      region was found. By Southern blot, it was established that these two
      amplification products contained sequences related to P. salmonis ITS. Sequence
      analysis confirmed that P. salmonis had two ITS regions: ITS A and ITS B. In both
      isolates, the smaller (ITS B) corresponded to ITS sequences previously described
      for each one, and the larger (ITS A) were almost the same as their respective ITS
      B sequences interrupted by an insert which contained two tRNAs genes: tRNA-Ile
      and tRNA-Ala.

PMID- 11287141
TI  - Shared antigenicity between Helicobacter pylori and periodontopathic
      Campylobacter rectus strains.
AB  - Periodontopathic Campylobacter rectus strains possess 41- and 68-kDa
      proteinaceous antigens which share antigenicity with antigens of Helicobacter
      pylori strains. H. pylori strains have a 54-kDa antigen which reacts with C.
      rectus strains. We found that the salivary IgA levels against H. pylori were
      correlated with those against C. rectus. These cross-reactive antigens of C.
      rectus may affect the serological diagnosis of H. pylori infections, especially
      when saliva is used. It is possible that these cross-reacting antigens may relate
      to the induction of immunopathological responses against both microorganisms.

PMID- 11287142
TI  - Application of gel microdroplet and flow cytometry techniques to selective
      enrichment of non-growing bacterial cells.
AB  - We describe an application of gel microdroplet (GMD) and flow cytometry
      techniques to selective enrichment of non-growing Leuconostoc mesenteroides
      cells, which are well culturable on other media, from a mixture with Bacillus
      subtilis cells in nutrient broth. After encapsulating cells of the mixed
      population within GMDs and a brief incubation in nutrient broth, the inability of
      L. mesenteroides cells to form microcolonies within GMDs allowed their
      discrimination from B. subtilis cells. After staining the GMD mixture with 6
      carboxyfluorescein diacetate, which showed no influence on cell viability, the
      GMDs containing single cells of L. mesenteroides were selectively collected using
      flow cytometry sorting based on differences in fluorescence intensity. The cells
      of L. mesenteroides retained viability during the process.

PMID- 11287143
TI  - Xanthomonas oryzae pv. oryzae recA is transcribed and regulated from multiple
      promoters.
AB  - Transcription regulation of Xanthomonas oryzae pv. oryzae recA was characterized.
      Primer extension experiments showed that recA is transcribed from three promoters
      designated P1, P2 and P3. The sequences of -10 and -35 regions of these promoters
      have moderate homology to the proposed consensus sequence for a Xanthomonas
      promoter. Putative SOS boxes were identified in the vicinity of P1 and P2
      promoters. Deletion analysis and in vivo monitoring of promoter activity of these
      promoters revealed that the three promoters have different characteristics. P1
      and P2 show stress-inducible high and low promoter strengths respectively. P3 is
      a non-inducible moderate promoter strength. These promoters are regulated by two
      SOS boxes. The multiplicity of promoters and SOS boxes provides back-up systems
      to ensure proper regulation of recA.

PMID- 11287144
TI  - Anaerobiosis induces complex changes in sterol esterification pattern in the
      yeast Saccharomyces cerevisiae.
AB  - Yeast Saccharomyces cerevisiae is auxotrophic for ergosterol in the absence of
      oxygen. We showed that complex changes in esterification of exogenously supplied
      sterols were also induced by anaerobiosis. Utilization of oleic acid for sterol
      esterification was significantly impaired in anaerobic cells. Furthermore,
      anaerobic cells fed different sterols exhibited striking variation in
      esterification efficiency (high levels of sterol esters for cholesterol and
      sitosterol, low levels for ergosterol, lanosterol or stigmasterol). Relative
      activities of two yeast acylCoA:sterol acyltransferases (Are1p and Are2p) changed
      in response to anaerobiosis: while Are2p was dominant under aerobic conditions,
      Are1p provided the major activity in the absence of oxygen. Our results indicate
      that sterol esters may fulfil different roles in aerobic and anaerobic cells.

PMID- 11287145
TI  - CytK toxin of Bacillus cereus forms pores in planar lipid bilayers and is
      cytotoxic to intestinal epithelia.
AB  - CytK is a cytotoxin isolated from a strain of Bacillus cereus cultured from cases
      of necrotic enteritis and the amino acid sequence of the protein suggests that it
      may belong to the family of beta-barrel pore-forming toxins. We show here in
      planar lipid bilayers the toxin is able to form pores which are weakly anion
      selective and exhibit an open channel probability close to one. The predicted
      minimum pore diameter is approximately 7 A. We also show that cytK is a potent
      cytotoxin against human intestinal Caco-2 epithelia. CytK, like other beta-barrel
      pore-forming toxins, spontaneously forms oligomers which are resistant to sodium
      dodecyl sulphate (SDS), but not to boiling. CytK represents a pore-forming toxin
      linked with human cases of necrotic enteritis.

PMID- 11287146
TI  - Molecular cloning, nucleotide sequence and structural analysis of the
      Streptomyces galbus DSM40480 fda gene: the S. galbus fructose-1,6-bisphosphate
      aldolase is a member of the class II aldolases.
AB  - The fda gene of Streptomyces galbus DSM40480 encoding the fructose-1,6
      bisphosphate aldolase (EC 4.1.2.13) was cloned, sequenced and characterised. The
      fda gene encodes a protein of 341 amino acids with a molecular mass of 36.5 kDa
      and belongs to the class II aldolases. When the S. galbus fda gene was expressed
      in the Escherichia coli fda(ts) mutant NP315, the growth defect of the strain was
      complemented at temperatures >35 degrees C. In Northern hybridisations, we
      identified an fda transcript of 1200 bp length. The transcript length indicates
      that the fda gene is transcribed from its own promoter. Attempts to isolate fda
      knock out mutants were not successful. Streptomyces lividans strains with a
      second copy of the fda gene were constructed and analysed.

PMID- 11287147
TI  - Heat-labile proteases in molecular biology applications.
AB  - Thermolabile proteases were identified in three Gram-negative psychrotrophic
      bacteria. The protease from the psychrotrophic strain A9 was purified and its
      application to common molecular biology techniques was demonstrated. Heat-stable
      molecular biology enzymes (Taq polymerase and PvuII) were digested by a heat
      labile protease, which was then inactivated by a mild heat treatment. The clear
      benefit of using heat-labile proteases arises in situations where further
      reactions may be accomplished without an intermediate purification step, thereby
      saving time and avoiding the possibility of product loss.

PMID- 11287148
TI  - The carboxy-terminal tail of the Ste2 receptor is involved in activation of the G
      protein in the Saccharomyces cerevisiae alpha-pheromone response pathway.
AB  - The Ste2 gene encodes the yeast alpha-pheromone receptor that belongs to the
      superfamily of seven-transmembrane G protein-coupled receptors. Binding of
      pheromone induces activation of the heterotrimeric G protein triggering growth
      arrest in G1 phase and induction of genes required for mating. By random PCR
      mediated mutagenesis we isolated mutant 8L4, which presents a substitution of an
      asparagine residue by serine at position 388 of the alpha-factor receptor. The
      8L4 mutant strain shows phenotypic defects such as: reduction in growth arrest
      after pheromone treatment, diminished activation of the Fus1 gene, and impaired
      mating competence. The asparagine residue lies in the second half of the
      intracellular protruding C-terminal tail of the receptor, and its replacement by
      serine affects interaction with both the G(alpha) and Gbeta subunits. Since
      expression of the receptor as well as its kinetic parameters, i.e., ligand
      affinity and receptor number, are unaffected in the mutant strain, we propose
      that association of the C-terminal tail of the receptor with G(alpha) and Gbeta
      subunits is required for proper activation of the heterotrimeric G protein.
      Besides its described role in downregulation and in formation of preactivation
      complex, the results here shown indicate that the C-terminal tail of the receptor
      plays an active role in transmitting the stimulus of mating pheromone to the
      heterotrimeric G protein.

PMID- 11287149
TI  - DDSE: downstream targets of the SNF3 signal transduction pathway.
AB  - Mutations in the yeast SNF3 gene affect glucose sensing and snf3 mutants show
      defective growth on glucose. DNA sequence dependent suppressing elements (DDSEs)
      are regions located in the promoters of yeast glucose transporter (HXT) genes
      that when present in high copy suppress the snf3 growth defect. Here we provide
      evidence that the multicopy DDSE suppression is due to the titration of the Rgt1p
      transcriptional repressor. The DDSE region from HXT4 was found to function as a
      UAS sequence rendering a UAS(gal)-less LacZ gene fused to the GAL1 promoter
      responsive to glucose induction. Expression mediated by the UAS(DDSE) was
      dependent upon the presence of Snf3p. Expression was elevated to a high level in
      an rgt1 mutant in the absence of Snf3p suggesting that this DDSE region contains
      binding sites for the Rgt1p transcriptional repressor/activator. The UAS(DDSE)
      led to expression in a grr1 mutant background, which confers a defect in
      inactivation of Rgt1p, as predicted from the model. The presence of tandem
      repeats of the putative Rgt1p binding site gave results similar to those of the
      DDSE, suggesting that loss of repression is due to the presence of Rgt1p
      footprint in the multicopy DDSE.

PMID- 11287150
TI  - Morphological and intracellular alterations induced by cytotoxin VT2y produced by
      Escherichia coli isolated from chickens with swollen head syndrome.
AB  - Recently, a novel verocytotoxin named VT2y was described which belongs to the STx
      family and is produced by Escherichia coli isolated from domestic poultry with
      swollen head syndrome (SHS). The VT2y toxin induced apoptosis in Vero, HeLa, CHO,
      CEF (primary chicken embryo fibroblast) and PCK (primary chicken kidney) cell
      lines. Morphological evidence (nuclear shrinkage, chromatin condensation and
      blebbing of the plasma membrane) of apoptosis could be distinguished in 15 min
      and was maximal at 1 h after treatment with VT2y. This was confirmed by the
      terminal dUTP nick-end-labeling (TUNEL) method.

PMID- 11287151
TI  - Characterization of the active-site residues asparagine 167 and lysine 161 of the
      IMP-1 metallo beta-lactamase.
AB  - The roles of lysine at position 161 and asparagine at position 167 in IMP-1
      metallo beta-lactamase were studied by site-directed mutagenesis. These residues
      are highly conserved in metallo beta-lactamases and are thought to be present in
      the active-site cavity. Mutant enzymes with alanine or aspartic acid at position
      167 showed almost the same properties as the wild-type enzyme. Kinetic parameters
      for the mutant enzymes differing at position 161 indicated that the positive
      charge of lysine 161 is required for electrostatic interaction with the carboxyl
      moiety of the substrate, i.e. C-3 of penicillins or C-4 of cephalosporins.

PMID- 11287152
TI  - FlhD/FlhC-regulated promoters analyzed by gene array and lacZ gene fusions.
AB  - The Escherichia coli transcriptional regulatory complex FlhD/FlhC, initially
      identified as a flagella-specific activator, is a global regulator involved in
      many cellular processes. Using gene arrays, lacZ gene fusions and enzyme assays,
      eight new targets of FlhD/FlhC were recognized. These are the transporter for
      galactose (MglBAC), the rod-shape determination proteins (MreBCD), malate
      dehydrogenase, and several enzymes involved in anaerobic respiration (glycerol 3
      phosphate dehydrogenase, GlpABC; periplasmic nitrate reductase, NapFAGHBC;
      nitrite reductase, NrfABCDEFG; dimethyl sulfoxide reductase, DmsABC; and the
      modulator for hydrogenases, HydNHypF).

PMID- 11287153
TI  - Formation of allyl isothiocyanate from sinigrin in the digestive tract of rats
      monoassociated with a human colonic strain of Bacteroides thetaiotaomicron.
AB  - A human digestive strain of Bacteroides thetaiotaomicron was tested for its
      ability to metabolise sinigrin, a glucosinolate commonly found in Brassica
      vegetables. Gnotobiotic rats harbouring the bacterial strain were orally dosed
      with 50 micromol sinigrin. HPLC analysis of the digestive contents showed that
      sinigrin was degraded in the large bowel, where B. thetaiotaomicron was
      established at a high level. Concurrently, a hydrolysis product of sinigrin,
      allyl isothiocyanate, was identified by GC-MS analysis, following headspace solid
      phase microextraction of the digestive contents; its production peaked at ca. 200
      nmol, 12 h after dosing. This is the first study to demonstrate in vivo the
      involvement of a human colonic predominant bacterium in the bioconversion of a
      dietary glucosinolate to a potentially anticarcinogenic isothiocyanate.

PMID- 11287154
TI  - Inhibition of phosphofructokinases by copper(II).
AB  - The biochemical inhibition by Cu2+ on eight phylogenetically and biochemically
      different phosphofructokinases (PFKs) was investigated. The enzymes screened
      included representatives from thermophilic and mesophilic bacteria, a
      hyperthermophilic archaeon and a eukaryote, covering all three phosphoryl donor
      subtypes (ATP, ADP and pyrophosphate). The sensitivities of the enzymes to Cu2+
      varied greatly, with the archaeal ADP-PFK being the least and the eukaryote ATP
      PFK being the most sensitive. The bacterial ATP- and pyrophosphate-dependent PFKs
      showed intermediate sensitivity with the exception of the Spirochaeta thermophila
      enzyme (pyrophosphate-dependent) which was relatively resistant.

PMID- 11287155
TI  - Analysis of pFQ31, a 8551-bp cryptic plasmid from the symbiotic nitrogen-fixing
      actinomycete Frankia.
AB  - The actinomycete Frankia has never been transformed genetically. To favour the
      development of Frankia cloning vectors, we have fully sequenced the Frankia alni
      pFQ31 cryptic plasmid and performed analyses to characterise its coding and non
      coding regions. This plasmid is 8551 bp-long and contains 72% G+C. Computer
      assisted analyses identified 18 open reading frames (ORFs). These ORFs show a
      synonymous codon usage different from the one of Frankia chromosomal genes,
      suggesting an evolutionary bias linked to the nature of the replicon or a
      horizontal transfer. Three ORFs were found to encode genes likely to be involved
      in plasmid replication and stability: parFA (partition protein), ptrFA
      (transcriptional repressor of the GntR family) and repFA (initiation of
      replication). DNA signatures of a replication origin were identified in the ptrFA
      repFA intergenic region. These structural motifs are similar to those observed
      among origins of iteron-containing plasmids replicating via a &theta; mode.

PMID- 11287156
TI  - Plasmid transfer and susceptibility to antibiotics in the halophilic phototrophs
      Rhodovibrio salinarum and Rhodothalassium salexigens.
AB  - The present study defines a series of genetic procedures to be used for molecular
      studies in photosynthetic halophilic species such as Rhodovibrio salinarum and
      Rhodothalassium salexigens. In both species, the minimal inhibitory
      concentrations for the antibiotics tetracycline, rifampicin, chloramphenicol,
      spectinomycin, streptomycin, and kanamycin were determined. In addition, conjugal
      transfer of IncP and IncQ plasmids from Escherichia coli was demonstrated and the
      resistance markers expressed in these halophiles were determined. Finally, Rth.
      salexigens growth dependence on variable salt concentrations was measured:
      maximal growth rates were seen at 6% and 4% NaCl under phototrophic and
      chemotrophic conditions, respectively. To the best of our knowledge, this is the
      first report analyzing the genetic properties of two representative species of
      halophilic purple non-sulfur phototrophs.

PMID- 11287157
TI  - The iron-regulated isiA gene of Fischerella muscicola strain PCC 73103 is linked
      to a likewise regulated gene encoding a Pcb-like chlorophyll-binding protein.
AB  - The expression of the chlorophyll a-binding, iron stress-induced protein IsiA is
      part of the cyanobacterial response to iron deficiency. A new isiA gene from the
      filamentous heterocystous cyanobacterial strain, Fischerella muscicola PCC 73103,
      was identified using standard and inverse PCR. While in unicellular
      cyanobacterial strains isiA is organized in an operon with isiB (encoding
      flavodoxin), in Fischerella not an isiB gene but another chlorophyll-binding
      protein encoding gene was identified downstream of isiA, which shows significant
      similarities to Pcb-like protein encoding genes known from prochlorophytes. The
      expression of both genes was clearly activated under iron deficiency. Although
      isiA and pcbC were independently transcribed, the size of the pcbC transcript
      indicates a large iron-regulated operon. Beside a 10-fold increase of isiA
      transcript content iron-starved cells of Fischerella showed a blue-shift in the
      red chlorophyll a absorption peak. In addition, chlorophyll fluorescence at 77 K
      was dominated by an emission peak at 685 nm. These features are in accordance
      with the characteristics of IsiA accumulation in iron-starved unicellular
      cyanobacteria, suggesting identical IsiA function in heterocystous strains in
      spite of different genetic organization.

PMID- 11287159
TI  - Basic principles of MRA.
AB  - Two types of MR angiography techniques are used in the radiological practice for
      neurovascular applications: flow based techniques and ultrafast contrast enhanced
      acquisitions. Both techniques have their specific advantages and limitations.
      Whereas flow based techniques can be run on most MR scanners, high quality
      contrast enhanced studies require a state-of-the-art system with high slew rates
      and dedicated tools to match bolus passage and MR scanning. In this text, we
      focus on the physical acquisition principles and we illustrate the different
      phenomena in clinical examples. Numerous studies have proven the clinical
      applications for the 2 acquisition strategies. So far, an understanding of the
      basic physics remains necessary to explain occasional artefacts: MR angiography
      techniques are not yet fully robust. Further optimizations of the current
      approaches can be expected as there is still a need to improve image quality.

PMID- 11287160
TI  - Magnetic resonance angiography of the intracranial vessels.
AB  - In this overview the results and indications of Magnetic Resonance Angiography of
      the intracranial vasculature will be discussed. The value of MRA will be studied
      in the visualisation of normal variants of the cerebral anatomy, the imaging of
      cerebrovascular disease, the diagnosis of aneurysms and cerebral arteriovenous
      malformations, the preoperative setup of cerebral tumors and the demonstration of
      vascular compression.

PMID- 11287161
TI  - Diffusion and perfusion MRI: basic physics.
AB  - Diffusion and perfusion MR imaging are now being used increasingly in neuro
      vascular clinical applications. While diffusion weighted magnetic resonance
      imaging exploits the translational mobility of water molecules to obtain
      information on the microscopic behaviour of the tissues (presence of
      macromolecules, presence and permeability of membranes, equilibrium intracellular
      extracellular water, ellipsis), perfusion weighted imaging makes use of
      endogenous and exogenous tracers for monitoring their hemodynamic status. The
      combination of both techniques is extremely promising for the early detection and
      assessment of stroke, for tumor characterisation and for the evaluation of
      neurodegenerative diseases. This article provides a brief review of the basic
      physics principles underlying the methodologies followed.

PMID- 11287162
TI  - Actual trends in diagnosis/thrombolytic therapy of acute cerebral stroke.
AB  - The recent reports confirm the idea that the selection of cerebral stroke
      patients for thrombolysis should be performed by MRI. These studies suggested
      that DWI/PWI/MRA may be able to identify patients who are most likely to benefit
      from thrombolytics, and that the PWI>DWI pattern in particular is associated with
      an improved outcome from thrombolytic therapy. However, many questions remain
      unanswered and a lot of work is necessary before MRI guided thrombolysis in acute
      cerebral stroke becomes a part of the standard care.

PMID- 11287164
TI  - Aplasia of bilateral uncinate processes with a bilateral nasomaxillary cavity.
AB  - Aplasia or hypoplasia of the uncinate process is associated with maxillary sinus
      aplasia or hypoplasia. It is of particular clinical importance to recognize the
      presence of normal or abnormal uncinate processes in patients who will undergo
      surgical procedures for paranasal sinus diseases. In this report, we present a
      case of aplasia of bilateral uncinate processes, discuss the variations of
      uncinate processes, and review related literature.

PMID- 11287163
TI  - Unusual changing CT and MR appearance of an epithelial intracranial cyst.
AB  - INTRODUCTION: Epithelial cysts are infrequent intracranial lesions and may
      content cilia and mucosecretant cells that may be responsible for the protein
      concentration within the contents and the variable radiological appearance on CT
      and MRI. METHODS AND PATIENTS: We present a case of an extraaxial epithelial cyst
      with changing CT and MR characteristics. RESULTS: The appearance of our cyst on
      CT or MRI changed with size and morphology. When CT studies showed an hypodense
      cyst, the lesion was large but when an hyperdense mass was present, the lesion
      was smaller. In the later situation MRI showed hyperintensity on T1-weighted
      images and hypointensity on T2-weighted images and the protein concentration of
      the cystic contents was high. CONCLUSIONS: We believe that a relatively high
      protein concentration in our cyst was the major factor for the high attenuation
      on CT and the hyperintensity or hypointensity on T1- and T2-weighted images,
      respectively. We believe than these atypical imaging findings were caused by
      changes in the protein concentration within the cyst.

PMID- 11287165
TI  - Transient MRI abnormalities associated with partial status epilepticus: a case
      report.
AB  - We report the case of an 18-year-old woman who presented a long-lasting cluster
      of partial seizures, and MRI cortical abnormalities localized in the left
      parietal lobe. The MRI changes correlated with the site of the epileptogenic
      focus, and disappeared within 2 weeks. The recognition of these reversible MRI
      abnormalities, which are presumably due to a temporary alteration of blood-brain
      barrier in the epileptogenic zone with subsequent edema, and are not associated
      with any underlying organic conditions, is extremely useful in the medical
      management of the patient and allows to avoid other invasive diagnostic
      procedures.

PMID- 11287166
TI  - Crossed cerebellar diaschisis in herpes simplex encephalitis.
AB  - Diaschisis is extremely rare in patients with viral encephalitis. We report the
      phenomenon of crossed cerebellar diaschisis (CCD) in a 73-year-old man with acute
      herpes simplex type-1 (HSV-1) encephalitis. The diagnosis of HSV-1 encephalitis
      was confirmed by detecting HSV-1 deoxyribonucleic acid in the cerebrospinal fluid
      (CSF). Magnetic resonance images (MRI) showed enhancing lesions at bilateral
      temporal lobes, insular cortices, and right frontoparietal lobes. Increase signal
      intensity on T2-weighted images was seen in the mesecephalon. Technetium-99m
      ethyl cysteinate dimer (99mTc-ECD) single photon emission computed tomography
      (SPECT) of the brain showed a large area of hypoperfusion in the right
      frontotemporoparietal lobes. The side-to-side cerebellar count revealed 19%
      reduction of the radioisotope tracer uptake in the left cerebellum. The
      phenomenon of CCD was proposed to be due to both anterograde disconnection of the
      corticopontocerebellar tracts and retrograde deafferentation of
      dentatothalamocortical projections.

PMID- 11287167
TI  - Spontaneous intracranial hypotension with diffuse dural enhancement of the spinal
      canal and transient enlargement of the pituitary gland.
AB  - Spontaneous intracranial hypotension is a rare phenomenon characterized by
      postural headache, neck rigidity, nausea and vomiting. Imaging findings on
      magnetic resonance imaging (MRI) is characteristic with diffuse intracranial
      pachymeningeal thickening and enhancement following intravenous gadolinium. We
      present a case of spontaneous intracranial hypotension with two unusual imaging
      findings; pachymeningeal enhancement of the spinal canal and enlargement of the
      pituitary gland in addition to the diffuse intracranial pachymeningeal
      enhancement. In this case report, we will discuss the clinical features, MRI
      findings and underlying pathophysiology of this rare condition.

PMID- 11287168
TI  - Comparison of two-dimensional gradient echo, turbo spin echo and two-dimensional
      turbo gradient spin echo sequences in MRI of the cervical spinal cord anatomy.
AB  - The aim of this study was to assess the detectability and distinguishability of
      the cervical spinal cord, the anterior and posterior spinal roots and of the
      internal anatomy of the cord (distinction of grey and white matter). For this
      purpose 20 healthy volunteers were examined using a 1.5 T MR unit with 20 mT/m
      gradient strength and a dedicated circular polarized neck array coil. Three T2*
      weighted (w). 2D gradient echo sequences, two T2 w. 2D turbo spin echo (TSE)
      sequences and one T2 w. 2D turbo gradient spin echo (TGSE) sequence were
      compared. The multiecho 2D fast low angle shot (FLASH) sequence with
      magnetization transfer saturation pulse (me FLASH+MTS) yielded the best results
      for liquor/compact bone, liquor/spinal cord and grey/white matter contrast, as
      found with regions of interest (ROI) analysis. The single echo 2D FLASH sequence
      was significantly poorer than the two me FLASH+/-MTS sequences. Two-dimensional
      TGSE as well as 2D TSE with a 256 matrix and with a 512 matrix yielded the
      poorest results. In the visual analysis the contrast between liquor and compact
      bone, liquor and cord as well as liquor and roots was best with me FLASH+MTS,
      whereas grey/white matter distinction was best using me FLASH-MTS. In conclusion,
      we would therefore recommend the inclusion of an axial T2* w. multiecho 2D
      spoiled gradient echo sequence with magnetization transfer saturation pulse and
      gradient motion rephasing in a MR imaging protocol of the cervical spine.

PMID- 11287169
TI  - Prediction of ocular irritancy of prototype shampoo formulations by the isolated
      rabbit eye (IRE) test and bovine corneal opacity and permeability (BCOP) assay.
AB  - The isolated rabbit eye (IRE) test and bovine corneal opacity and permeability
      (BCOP) assay were evaluated for their ability to predict the eye irritation
      potential of a range of hair shampoo formulations, some containing a novel non
      surfactant ingredient known to be an ocular irritant. The additional endpoints of
      corneal swelling and histological examination were incorporated into the standard
      BCOP protocol. Historic Draize data were available for several of the
      formulations and served as a reference. The standard BCOP assay (without
      histology) failed to distinguish between shampoos of low and high irritant
      potential, when exposure times of 10 and 60 min were employed (for undiluted and
      10% dilution of the shampoos, respectively) and the in vitro score classified the
      majority of formulations as mild. The incorporation of the histological endpoint
      to the BCOP protocol allowed discrimination between formulations of differing
      irritancy, and should be included to augment the standard BCOP protocol. Corneal
      swelling values did not, however, correlate with the irritant potential of the
      shampoos tested. The IRE which includes the endpoints of corneal swelling and
      histopathological scoring produced classifications of irritancy that were fairly
      consistent with in vivo data and distinguished between the high and low irritant
      potential shampoos.

PMID- 11287170
TI  - Mini mutagenicity test: a miniaturized version of the Ames test used in a
      prescreening assay for point mutagenesis assessment.
AB  - The bacterial reverse mutagenicity test on Salmonella typhimurium, known as the
      Ames test, is widely used by regulatory agencies, academic institutions and
      chemical companies to assess the mutagenic potential of raw compounds. Several
      attempts have been made to miniaturise the Ames test in order to fit the
      industrial constraint of screening more products at the low quantities available.
      The major limitation of these miniaturised versions of the Ames test lies in the
      impossibility to work with all the six strains used in the regular Ames test,
      especially with those showing a low spontaneous revertant frequency. We describe
      here a mini version of the regulatory Ames test protocol that allows a
      significant reduction of the quantity of test substance needed (300 mg) but
      remains applicable to all Salmonella strains used in the regulatory protocol. In
      a preliminary study, 10 in-house chemical compounds have been evaluated in the
      Mini Mutagenicity Test (MMT) together with some positive control substances. A
      first set of historical data obtained in 1999 as well as the predictivity and the
      sensitivity of the MMT are presented and compared to those of the regular Ames
      test.

PMID- 11287171
TI  - Extent of initial corneal injury as a basis for alternative eye irritation tests.
AB  - Based on studies that have characterized the extent of injury occurring with
      irritants of differing type and severity, we have proposed that extent of initial
      injury is the principal mechanism underlying ocular irritation. We report here
      our efforts to apply this hypothesis, as a mechanistic basis, to the development
      of an alternative eye irritation assay using an ex vivo rabbit corneal model.
      Rabbit eyes were obtained immediately after sacrifice or from an abattoir and 8.5
      mm diameter corneal buttons were removed and cultured overnight at an air-liquid
      interface under serum-free conditions. Buttons were exposed to materials of
      differing type (surfactant, acid, base, alcohol and aldehyde) and irritancy
      (slight to severe) that had been previously characterized microscopically in the
      rabbit low-volume eye test. Exposure was accomplished by applying 1.5 microl of
      an irritant to a sterile, 3 mm diameter, filter paper disk and then placing the
      disk on the center of the corneal button for 10 s. After removal of the disk,
      buttons were washed and cultured for 3, 24 or 48 h. Buttons were then evaluated
      for extent of injury using a Live/Dead staining kit and fluorescent microscopy to
      measure cell size of live surface epithelial cells, area of epithelial denudation
      and depth of stromal injury. Ex vivo exposure to slight irritants generally
      reduced surface epithelial cell size (i.e. erosion) while exposure to mild
      irritants produced epithelial denudation with variable injury to the corneal
      stroma. Severe irritants generally produced extensive epithelial denudation and
      damaged the corneal stroma and endothelium. Overall, ex vivo extent of injury
      significantly correlated with in vivo extent of injury as measured in previous
      animal tests (r=0.81, P<0.001). These findings indicate that extent of corneal
      injury, as shown to be associated with ocular irritation occurring in vivo, can
      be applied to the development of a mechanistically-based alternative eye
      irritation model. We believe that this approach may ultimately lead to an
      alternative assay to replace the use of animals in ocular irritation testing.

PMID- 11287172
TI  - Fluoroquinolones as chemical tools to define a strategy for photogenotoxicity in
      vitro assessment.
AB  - Today's lifestyle is often associated with frequent exposure to sunlight, but
      some xenobiotics used in drugs, cosmetics or food chemicals can produce adverse
      biological effects when irradiated. In particular, they can increase the risk of
      photogenotoxicity already due to UV radiation itself. There is thus a need to
      design appropriate approaches in order to obtain relevant data at the molecular
      and cellular level in this field. For ethical and practical reasons, in vitro
      models can be very convenient at least for first evaluation tests. Here, we
      propose a strategy based on complementary experiments to study the photogenotoxic
      potential of a compound. The fluoroquinolones BAYy3118 and lomefloxacin were used
      as standards to demonstrate the performance of each test: photoinduced
      interaction with supercoiled circular DNA, photomutagenicity in the yeast
      Saccharomyces cerevisae, induction of DNA photodamage in cultured human skin
      cells as revealed by comet assay, and finally induction of specific phototoxic
      stress responses such as p53 activation or melanogenesis stimulation. Such a
      strategy should help to ensure the safety of products likely to undergo
      environmental sunlight exposure.

PMID- 11287173
TI  - Herbicides and the microtubular apparatus of Nicotiana tabacum pollen tube:
      immunofluorescence and immunogold labelling studies.
AB  - Herbicides are chemical compounds widely used in agriculture. As their intensive
      application is becoming a cause of environmental pollution, detailed and more
      sophisticated investigations are needed to understand better their consequences
      at the biological level. After herbicides are dispersed in the fields, they
      establish chemical interactions with both target and non-target plants. In both
      cases, herbicides can interact with the plant reproductive apparatus;
      consequently they could play a role during the fertilisation process in higher
      plants. Using an antibody to the alpha-tubulin subunit in immunofluorescence and
      immunoelectron microscopy techniques, we investigated the distribution of
      microtubules in Nicotiana tabacum pollen tubes grown under in vitro conditions in
      the presence of five different herbicides selected among those used frequently in
      central Italy. Herbicides have a specific effect on the microtubular apparatus of
      both pollen tube and generative cell. In addition to other tests and assays,
      these results suggest that the microtubule cytoskeleton of pollen tubes can be
      used as a bioindicator for studying the toxicity effects induced by herbicides.

PMID- 11287174
TI  - In vitro long-term cytotoxicity testing of 27 MEIC chemicals on Hep G2 cells and
      comparison with acute human toxicity data.
AB  - Within the framework of the EDIT (Evaluation guided Development of In vitro
      Toxicity and toxicokinetic tests) programme, the long-term cytotoxicity of 27
      chemicals was investigated on Hep G2 cells. The first step in the experiments was
      to determine the PI50(24h) of the chemicals. This is the concentration of
      compound needed to reduce the total protein content by 50% after 24 h of
      treatment. In the long-term experiments the chemicals were tested in six
      different concentrations, using the PI50(24h) as maximum concentration. The cells
      were treated twice a week with the same concentration of test compound and were
      trypsinised and counted once a week (dynamic culture). The number of cells was
      compared to the number of cells of the control. Three major long-term
      cytotoxicity patterns could be distinguished. After 6 weeks, the EC50(6w)s were
      determined. This is the concentration of compound needed to reduce the number of
      cells by 50% after 6 weeks of treatment. These values were compared with the
      PI50(24h). A good correlation was found for the 27 chemicals (r(2)=0.860). After
      6 weeks, the concentration of test compound needed to reduce the total cell
      protein content by 50% after 24 h after 6 weeks of pretreatment of the cells with
      a particular concentration of test compound was measured: the PI50(24h-6w). For
      the majority of compounds there is no difference between the PI50(24h) and the
      PI50(24h-6w). For ethanol, arsenic (III) oxide, verapamil hydrochloride and
      orphenadrine, the PI50(24h-6w) increased in comparison to the PI50(24h). For some
      compounds a doseresponse was observed, indicating that the cells have become more
      resistant or more sensitive. Linear regression analysis revealed a good
      correlation (r(2)=0.709) between the EC50(6w) and the human acute toxicity. All
      these data indicate that a good alternative test may be found for predicting the
      long-term human toxicity.

PMID- 11287175
TI  - Effect of O(2)/O(3) atmosphere on the rate of osmotic hemolysis of bovine
      erythrocytes in the presence of some antioxidants.
AB  - Purified red blood cells, exposed to an ozone atmosphere, show an increased rate
      of hemolysis on sudden osmotic stress. To determine this effect of ozone in the
      presence of natural antioxidants, bovine red blood cells, used as models, were
      suspended in blood plasma, or in physiological saline with one of the following
      antioxidants: albumin, glutathione, uric acid, glucose and a vitamin E analog
      (trolox). After exposure of the suspensions to oxygen and oxygen/ozone
      atmospheres the rates of osmotic hemolysis were measured, using a stop-flow
      technique, and compared with rates measured in air-exposed controls. Blood
      plasma, containing all natural antioxidants, caused a decreased rate of osmotic
      hemolysis of cells exposed to oxygen and also decreased the effect of ozone.
      Trolox cancelled the oxygen effects only. Albumin, glutathione and uric acid
      tended to protect the cells from the hemolytic effects of ozone. The
      antihemolytic effect of glucose, seen only in some samples, may depend on
      uncontrolled factors. The alteration of the rates correlates with an increased
      fluidity of red cell membranes exposed to ozone.

PMID- 11287176
TI  - Effects of p,p'-DDE on immature cells in culture at concentrations relevant to
      the Alaskan environment.
AB  - Arctic Alaskan Natives who maintain a traditional lifestyle have a disease
      profile that is significantly different from the general US population. There is
      concern that food sources containing environmental pollutants may contribute to
      this profile. In a preliminary study, umbilical cord blood was examined for the
      presence of several environmental contaminants. All cord blood samples analyzed
      thus far contain p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) with an
      average concentration of 0.33 microg/l. This study was undertaken to ascertain if
      this concentration of p,p'-DDE had detectable effects on immature cells in
      culture. NIH 3T3 (embryonic mouse fibroblast) and WS1 (human fetal fibroblast)
      cultures were exposed to media containing either 1 or 10 times the average cord
      blood concentration of p,p'-DDE. Initial experiments indicated that exposure to
      p,p'-DDE resulted in a decrease in the cell number of both cell types. Subsequent
      analysis revealed that the decrease in cell number was due to cell death in NIH
      3T3 cells and to cell-cycle arrest in WS1 cells. Furthermore, p,p'-DDE decreased
      the long-term survival of NIH 3T3 but not WS1 cells. This study has demonstrated
      that p,p'-DDE, at relevant environmental concentrations, has significant effects
      on two immature mammalian cell types in culture. In addition, these results
      highlight the necessity for further studies to address the specific effects of
      p,p'-DDE on developing fetal systems.

PMID- 11287177
TI  - Cross-regulation of Hox genes in the Drosophila melanogaster embryo.
AB  - Cross-regulation of Homeotic Complex (Hox) genes by ectopic Hox proteins during
      the embryonic development of Drosophila melanogaster was examined using Gal4
      directed transcriptional regulation. The expression patterns of the endogenous
      Hox genes were analyzed to identify cross-regulation while ectopic expression
      patterns and timing were altered using different Gal4 drivers. We provide
      evidence for tissue specific interactions between various Hox genes and
      demonstrate the induction of endodermal labial (lab) by ectopically expressed
      Ultrabithorax outside the visceral mesoderm (VMS). Similarly, activation and
      repression of Hox genes in the VMS from outside tissues seems to be mediated by
      decapentaplegic (dpp) gene activation. Additionally, we find that proboscipedia
      (pb) is activated in the epidermis by ectopically driven Sex combs reduced (Scr)
      and Deformed (Dfd); however, mesodermal pb expression is repressed by ectopic Scr
      in this tissue. Mutant analyses demonstrate that Scr and Dfd regulate pb in their
      normal domains of expression during embryogenesis. Ectopic Ultrabithorax and
      Abdominal-A repress only lab and Scr in the central nervous system (CNS) in a
      timing dependent manner; otherwise, overlapping expression in the CNS in
      tolerated. A summary of Hox gene cross-regulation by ectopically driven Hox
      proteins is tabulated for embryogenesis.

PMID- 11287178
TI  - Homeotic Complex (Hox) gene regulation and homeosis in the mesoderm of the
      Drosophila melanogaster embryo: the roles of signal transduction and cell
      autonomous regulation.
AB  - In this paper we evaluate homeosis and Homeotic Complex (Hox) regulatory
      hierarchies in the somatic and visceral mesoderm. We demonstrate that both Hox
      control of signal transduction and cell autonomous regulation are critical for
      establishing normal Hox expression patterns and the specification of segmental
      identity and morphology. We present data identifying novel regulatory
      interactions associated with the segmental register shift in Hox expression
      domains between the epidermis/somatic mesoderm and visceral mesoderm. A proposed
      mechanism for the gap between the expression domains of Sex combs reduced (Scr)
      and Antennapedia (Antp) in the visceral mesoderm is provided. Previously, Hox
      gene interactions have been shown to occur on multiple levels: direct cross
      regulation, competition for binding sites at downstream targets and through
      indirect feedback involving signal transduction. We find that extrinsic
      specification of cell fate by signaling can be overridden by Hox protein
      expression in mesodermal cells and propose the term autonomic dominance for this
      phenomenon.

PMID- 11287179
TI  - Mice with a homozygous gene trap vector insertion in mgcRacGAP die during pre
      implantation development.
AB  - In a phenotypic screen in mice using a gene trap approach in embryonic stem
      cells, we have identified a recessive loss-of-function mutation in the mgcRacGAP
      gene. Maternal protein is present in the oocyte, and mgcRacGAP gene transcription
      starts at the four-cell stage and persists throughout mouse pre-implantation
      development. Total mgcRacGAP deficiency results in pre-implantation lethality.
      Such E3.5 embryos display a dramatic reduction in cell number, but undergo
      compaction and form a blastocoel. At E3.0-3.5, binucleated blastomeres in which
      the nuclei are partially interconnected are frequently observed, suggesting that
      mgcRacGAP is required for normal mitosis and cytokinesis in the pre-implantation
      embryo. All homozygous mutant blastocysts fail to grow out on fibronectin-coated
      substrates, but a fraction of them can still induce decidual swelling in vivo.
      The mgcRacGAP mRNA expression pattern in post-implantation embryos and adult
      mouse brain suggests a role in neuronal cells. Our results indicate that
      mgcRacGAP is essential for the earliest stages of mouse embryogenesis, and add
      evidence that CYK-4-like proteins also play a role in microtubule-dependent steps
      in the cytokinesis of vertebrate cells. In addition, the severe phenotype of null
      embryos indicates that mgcRacGAP is functionally non-redundant and cannot be
      substituted by other GAPs during early cleavage of the mammalian embryo.

PMID- 11287181
TI  - Identification of essential sequence motifs in the node/notochord enhancer of
      Foxa2 (Hnf3beta) gene that are conserved across vertebrate species.
AB  - The expression of a winged-helix transcription factor, Foxa2/HNF3beta, is
      essential for development of the node and the notochord. We examined the
      node/notochord enhancer of mouse Foxa2 for sequence motifs conserved across
      vertebrate species. We cloned Foxa2 genes from chicken and fish, and identified
      the respective node/notochord enhancers that were active in transgenic mouse
      embryos. Comparison of the sequences of the enhancers revealed three
      evolutionally conserved sequence motifs, CS1, CS2 and CS3. Mutational analysis of
      the mouse enhancer indicated that CS3 is indispensable for gene expression in the
      node and the notochord, while CS1 and CS2 are required to augment enhancer
      activity. These motifs do not correspond to the consensus binding sequences of
      transcription factors known to be involved in node/notochord development.

PMID- 11287180
TI  - Secreted Frizzled-related proteins can regulate metanephric development.
AB  - Wnt-4 signaling plays a critical role in kidney development and is associated
      with the epithelial conversion of the metanephric mesenchyme. Furthermore,
      secreted Frizzled-related proteins (sFRPs) that can bind Wnts are normally
      expressed in the developing metanephros, and function in other systems as
      modulators of Wnt signaling. sfrp-1 is distributed throughout the medullary and
      cortical stroma in the metanephros, but is absent from condensed mesenchyme and
      primitive tubular epithelia of the developing nephron where wnt-4 is highly
      expressed. In contrast, sfrp-2 is expressed in primitive tubules. To determine
      their role in kidney development, recombinant sFRP-1, sFRP-2 or combinations of
      both were applied to cultures of 13-dpc rat metanephroi. Both tubule formation
      and bud branching were markedly inhibited by sFRP-1, but concurrent sFRP-2
      treatment restored some tubular differentiation and bud branching. sFRP-2 itself
      showed no effect on cultures of metanephroi. In cultures of isolated, induced rat
      metanephric mesenchymes, sFRP-1 blocked events associated with epithelial
      conversion (tubulogenesis and expression of lim-1, sfrp-2 and E-cadherin);
      however, it had no demonstrable effect on early events (compaction of mesenchyme
      and expression of wt1). As shown herein, sFRP-1 binds Wnt-4 with considerable
      avidity and inhibits the DNA-binding activity of TCF, an effector of Wnt
      signaling, while sFRP-2 had no effect on TCF activation. These observations
      suggest that sFRP-1 and sFRP-2 compete locally to regulate Wnt signaling during
      renal organogenesis. The antagonistic effect of sFRP-1 may be important either in
      preventing inappropriate development within differentiated areas of the medulla
      or in maintaining a population of cortical blastemal cells to facilitate further
      renal expansion. On the other hand, sFRP-2 might promote tubule formation by
      permitting Wnt-4 signaling in the presence of sFRP-1.

PMID- 11287182
TI  - The role of the Drosophila TAK homologue dTAK during development.
AB  - The TAK kinases belong to the MAPKKK group and have been implicated in a variety
      of signaling events. Originally described as a TGF-beta activated kinase (TAK) it
      has, however, subsequently been demonstrated to signal through p38, Jun N
      terminal kinase (JNK) and Nemo types of MAP kinases, and the NFkappaB inducing
      kinase. Despite these multiple proposed functions, the in vivo role of TAK family
      kinases remains unclear. Here we report the isolation and genetic
      characterization of the Drosophila TAK homologue (dTAK). By employing
      overexpression and double-stranded RNA interference (RNAi) techniques we have
      analyzed its function during embryogenesis and larval development. Overexpression
      of dTAK in the embryonic epidermis is sufficient to induce the transcription of
      the JNK target genes decapentaplegic and puckered. Furthermore, overexpression of
      dominant negative (DN) or wild-type forms of dTAK in wing and eye imaginal discs,
      respectively, results in defects in thorax closure and ommatidial planar
      polarity, two well described phenotypes associated with JNK signaling activity.
      Surprisingly, RNAi and DN-dTAK expression studies in the embryo argue for a
      differential requirement of dTAK during developmental processes controlled by JNK
      signaling, and a redundant or minor role of dTAK in dorsal closure. In addition,
      dTAK-mediated activation of JNK in the Drosophila eye imaginal disc leads to an
      eye ablation phenotype due to ectopically induced apoptotic cell death. Genetic
      analyses in the eye indicate that dTAK can also act through the p38 and Nemo
      kinases in imaginal discs. Our results suggest that dTAK can act as a JNKKK
      upstream of JNK in multiple contexts and also other MAPKs in the eye. However,
      the loss-of-function RNAi studies indicate that it is not strictly required and
      thus either redundant or playing only a minor role in the context of embryonic
      dorsal closure.

PMID- 11287183
TI  - Evidence that SPROUTY2 functions as an inhibitor of mouse embryonic lung growth
      and morphogenesis.
AB  - Experimental evidence is rapidly emerging that the coupling of positive
      regulatory signals with the induction of negative feedback modulators is a
      mechanism of fine regulation in development. Studies in Drosophila and chick have
      shown that members of the SPROUTY family are inducible negative regulators of
      growth factors that act through tyrosine kinase receptors. We and others have
      shown that Fibroblast Growth Factor 10 (FGF10) is a key positive regulator of
      lung branching morphogenesis. Herein, we provide direct evidence that mSprouty2
      is dynamically expressed in the peripheral endoderm in embryonic lung and is
      downregulated in the clefts between new branches at E12.5. We found that
      mSprouty2 was expressed in a domain restricted in time and space, adjacent to
      that of Fgf10 in the peripheral mesenchyme. By E14.5, Fgf10 expression was
      restricted to a narrow domain of mesenchyme along the extreme edges of the
      individual lung lobes, whereas mSprouty2 was most highly expressed in the
      subjacent epithelial terminal buds. FGF10 beads upregulated the expression of
      mSprouty2 in adjacent epithelium in embryonic lung explant culture. Lung cultures
      treated with exogenous FGF10 showed greater branching and higher levels of mSpry2
      mRNA. Conversely, Fgf10 antisense oligonucleotides reduced branching and
      decreased mSpry2 mRNA levels. However, treatment with exogenous FGF10 or
      antisense Fgf10 did not change Shh and FgfR2 mRNA levels in the lungs. We
      investigated Sprouty2 function during lung development by two different but
      complementary approaches. The targeted overexpression of mSprouty2 in the
      peripheral lung epithelium in vivo, using the Surfactant Protein C promoter,
      resulted in a low level of branching, lung lobe edges abnormal in appearance and
      the inhibition of epithelial proliferation. Transient high-level overexpression
      of mSpry2 throughout the pulmonary epithelium by intra-tracheal adenovirus
      microinjection also resulted in a low level of branching. These results indicate
      for the first time that mSPROUTY2 functions as a negative regulator of embryonic
      lung morphogenesis and growth.

PMID- 11287185
TI  - Role of QN1 protein in cell proliferation arrest and differentiation during the
      neuroretina development.
AB  - In this report, we describe the involvement of the quail neuroretina 1 (QN1)
      protein in retinal development. The Qn1 cDNA was isolated as a gene specifically
      expressed at the onset of neuronal cell cycle withdrawal (Bidou et al., Mech.
      Dev. 43 (1993) 159). Qn1 is located in the cytoplasm in proliferating cells
      during the early stages of the development. Its distribution changes, becoming
      predominantly nuclear, in neurons during establishment of the quiescent state
      upon the differentiation. We decreased the amount of QN1 protein by an antisense
      strategy in vitro or in vivo. This decrease of the amount of QN1 protein results
      in additional mitosis and in severe abnormalities such as retinal dysplasia. Our
      results suggest that QN1 plays a key role at the onset of neuronal cell cycle
      withdrawal.

PMID- 11287184
TI  - Involvement of EphA2 in the formation of the tail notochord via interaction with
      ephrinA1.
AB  - Eph receptors have been implicated in cell-to-cell interaction during
      embryogenesis. We generated EphA2 mutant mice using a gene trap method.
      Homozygous mutant mice developed short and kinky tails. In situ hybridization
      using a Brachyury probe found the notochord to be abnormally bifurcated at the
      caudal end between 11.5 and 12.5 days post coitum. EphA2 was expressed at the tip
      of the tail notochord, while one of its ligands, ephrinA1, was at the tail bud in
      normal mice. In contrast, EphA2-deficient notochordal cells were spread broadly
      into the tail bud. These observations suggest that EphA2 and its ligands are
      involved in the positioning of the tail notochord through repulsive signals
      between cells expressing these molecules on the surface.

PMID- 11287186
TI  - Screening from a subtracted embryonic chick hindbrain cDNA library:
      identification of genes expressed during hindbrain, midbrain and cranial neural
      crest development.
AB  - The vertebrate hindbrain is segmented into a series of transient structures
      called rhombomeres. Despite knowing several factors that are responsible for the
      segmentation and maintenance of the rhombomeres, there are still large gaps in
      understanding the genetic pathways that govern their development. To find
      previously unknown genes that are expressed within the embryonic hindbrain, a
      subtracted chick hindbrain cDNA library has been made and 445 randomly picked
      clones from this library have been analysed using whole mount in situ
      hybridisation. Thirty-six of these clones (8%) display restricted expression
      patterns within the hindbrain, midbrain or cranial neural crest and of these,
      twenty-two are novel and eleven encode peptides that correspond to or are highly
      related to proteins with previously uncharacterised roles during early neural
      development. The large proportion of genes with restricted expression patterns
      and previously unknown functions in the embryonic brain identified during this
      screen provides insights into the different types of molecules that have
      spatially regulated expression patterns in cranial neural tissue.

PMID- 11287187
TI  - Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse
      gonad development and represses expression of Ad4BP/SF-1.
AB  - Mammalian sex-determination and differentiation are controlled by several genes,
      such as Sry, Sox-9, Dax-1 and Mullerian inhibiting substance (MIS), but their
      upstream and downstream genes are largely unknown. Ad4BP/SF-1, encoding a zinc
      finger transcription factor, plays important roles in gonadogenesis. Disruption
      of this gene caused disappearance of the urogenital system including the gonad.
      Ad4BP/SF-1, however, is also involved in the sex differentiation of the gonad at
      later stages, such as the regulation of steroid hormones and MIS. Pod-1/Capsulin,
      a member of basic helix-loop-helix transcription factors, is expressed in a
      pattern closely related but mostly complimentary to that of the Ad4BP/SF-1
      expression in the developing gonad. In the co-transfection experiment using
      cultured cells, overexpression of Pod-1/Capsulin repressed expression of a
      reporter gene that carried the upstream regulatory region of the Ad4BP/SF-1 gene.
      Furthermore, forced expression of Pod-1/Capsulin repressed expression of Ad4BP/SF
      1 in the Leydig cell-derived I-10 cells. These results suggest that Pod
      1/Capsulin may play important roles in the development and sex differentiation of
      the mammalian gonad via transcriptional regulation of Ad4BP/SF-1.

PMID- 11287188
TI  - Mechanisms of transcriptional activation of the col6a1 gene during Schwann cell
      differentiation.
AB  - A transgenic mouse line expressing the lacZ reporter under the control of a
      regulatory region of the col6a1 gene has been used to investigate differentiation
      of Schwann cells. The data suggest that: (1) activation of col6a1 gene
      transcription in the peripheral nervous system is part of the differentiation
      program of Schwann cells from neural crest cells stimulated by neuregulins; (2)
      once the Schwann cell precursors have acquired the competence of transcribing the
      col6a1 gene, transcriptional regulation becomes independent from neuregulins and
      is modulated by different mechanisms, including cell cycle; (3) activation of
      transgene expression after birth in sciatic nerves corresponds to the time of
      withdrawal of immature Schwann cells from the cell cycle and the beginning of
      their differentiation into myelinating Schwann cells.

PMID- 11287189
TI  - Xenopus Enhancer of Zeste (XEZ); an anteriorly restricted polycomb gene with a
      role in neural patterning.
AB  - We have identified the Xenopus homologue of Drosophila Enhancer of Zeste using a
      differential display strategy designed to identify genes involved in early
      anterior neural differentiation. XEZ codes for a protein of 748 amino acids that
      is very highly conserved in evolution and is 96% identical to both human and
      mouse EZ(H)2. In common with most other Xenopus Pc-G genes and unlike mammalian
      Pc-G genes, XEZ is anteriorly restricted. Zygotic expression of XEZ commences
      during gastrulation, much earlier than other anteriorly localized Pc-G genes;
      expression is restricted to the anterior neural plate and is confined later to
      the forebrain, eyes and branchial arches. XEZ is induced in animal caps
      overexpressing noggin; up-regulation of XEZ therefore represents a response to
      inhibition of BMP signalling in ectodermal cells. We show that the
      midbrain/hindbrain junction marker En-2,and hindbrain marker Krox-20, are target
      genes of XEZ and that XEZ functions to repress these anteroposterior marker
      genes. Conversely, XEZ does not repress the forebrain marker Otx-2. XEZ
      overexpression results in a greatly thickened floor of the forebrain. These
      results implicate an important role for XEZ in the patterning of the nervous
      system.

PMID- 11287190
TI  - Characterization of mouse Dach2, a homologue of Drosophila dachshund.
AB  - The Drosophila genes eyeless, eyes absent, sine oculis and dachshund cooperate as
      components of a network to control retinal determination. Vertebrate homologues
      of these genes have been identified and implicated in the control of cell fate.
      We present the cloning and characterization of mouse Dach2, a homologue of
      dachshund. In situ hybridization studies demonstrate Dach2 expression in
      embryonic nervous tissues, sensory organs and limbs. This pattern is similar to
      mouse Dach1, suggesting a partially redundant role for these genes during
      development. In addition, we determine that Dach2 expression in the forebrain of
      Pax6 mutants and dermamyotome of Pax3 mutants is not detectably altered. Finally,
      genetic mapping experiments place mouse Dach2 on the X chromosome between Xist
      and Esx1. The identification of human DACH2 sequences at Xq21 suggests a possible
      role for this gene in Allan-Herndon syndrome, Miles-Carpenter syndrome, X-linked
      cleft palate and/or Megalocornea.

PMID- 11287191
TI  - Distinct domains mediate the early and late functions of the Drosophila ovarian
      tumor proteins.
AB  - The Drosophila melanogaster ovarian tumor (otu) gene encodes two novel protein
      isoforms that are required at multiple stages of oogenesis. We have examined the
      activity of a set of C-terminal truncation Otu proteins as well as a GFP-tagged
      Otu (Otu-GFP). These experiments have shown that a putative Tudor domain in the
      central region of the large Otu isoform and a separate domain in the C-terminal
      region are required for regulation of cyst formation and oocyte maturation,
      respectively. We also present evidence that a portion of Otu co-fractionates with
      mRNA/protein complexes (mRNPs) and show that Otu-GFP associates with cytoplasmic
      aggregates at periphery of the nucleus at an intermediate stage of oogenesis.
      This study substantially clarifies the relationship between Otu structure and
      function and reveals new clues about interacting components.

PMID- 11287192
TI  - The RHG motifs of Drosophila Reaper and Grim are important for their distinct
      cell death-inducing abilities.
AB  - Reaper, Hid, and Grim are three Drosophila cell death activators that each
      contain a conserved NH(2)-terminal Reaper, Hid, Grim (RHG) motif. We have
      analyzed the importance of the RHG motifs in Reaper and Grim for their different
      abilities to activate cell death during development. Analysis of chimeric R/Grim
      and G/Reaper proteins indicated that the Reaper and Grim RHG motifs are
      functionally distinct and help to determine specific cell death activation
      properties. A truncated GrimC protein lacking the RHG motif retained an ability
      to induce cell death, and unlike Grim, R/Grim, or G/Reaper, its actions were not
      efficiently blocked by the cell death inhibitors, Diap1, Diap2, p35, or a
      dominant/negative Dronc caspase. Finally, we identified a second region of
      sequence similarity in Reaper, Hid, and Grim, that may be important for shared
      RHG motif-independent activities.

PMID- 11287193
TI  - Net, an Ets ternary complex transcription factor, is expressed in sites of
      vasculogenesis, angiogenesis, and chondrogenesis during mouse development.
AB  - The Net gene encodes an Ets transcription factor belonging to the ternary complex
      factor subfamily. We studied Net expression during mouse development (E7.5-E18.5)
      by in situ hybridization. Net is expressed at E7.5-8.5 in developing vascular
      primordia, including the allantoic vessels, heart endocardium and dorsal aortae.
      Vascular endothelial cell expression persists throughout development. Additional
      sites of expression appear at E9.5-E10.5, especially in facial, branchial arch
      and distal limb-bud mesenchyme. Later, expression is most conspicuous in
      developing cartilage and becomes progressively restricted to perichondrium. Net
      expression during mouse development correlates with vasculogenesis, angiogenesis
      and cartilage ontogeny.

PMID- 11287194
TI  - Expression of a novel mammalian epidermal growth factor-related gene during mouse
      neural development.
AB  - We have recently reported the preliminary characterisation of a novel EGF-related
      gene, Scube1 (signal peptide-CUB domain-EGF-related, gene 1), that is expressed
      prominently in the developing gonad, nervous system, somites, surface ectoderm
      and limb buds of the mouse. Here we describe the expression pattern of a closely
      related gene, Scube2 (also known as Cegp1), which maps to the distal region of
      mouse chromosome 7. Scube2 transcription is restricted to the embryonic
      neurectoderm but is also detectable in the adult heart, lung and testis.

PMID- 11287195
TI  - fgfr3 and regionalization of anterior neural tube in zebrafish.
AB  - Here we describe the isolation of the zebrafish fgfr3 gene, its structure and
      chromosomal location. Expression in wild type embryos occurs in the axial
      mesoderm, the diencephalon, the anterior hindbrain and the anterior spinal cord.
      In the hindbrain, a differential expression of fgfr3 was detected at several
      levels of intensity, with the highest expression in the posterior rhombomere 1
      that is morphologically distinct from the anterior part, which develops into the
      cerebellum. Further, analysis of fgfr3 expression in mutants deficient in the
      formation of the midbrain-hindbrain boundary (MHB), noi(-/-) and ace(-/-),
      demonstrated that in the absence of Pax2.1 and FGF8 activity, the expression
      domains of FGFR3 expand into the MHB, tegmentum, cerebellum and optic tectum,
      which are the affected structures in these mutants.

PMID- 11287196
TI  - NSPc1, a novel mammalian Polycomb gene, is expressed in neural crest-derived
      structures of the peripheral nervous system.
AB  - Anterior-posterior (A-P) patterning is a key element in early embryonic
      development. Polycomb group (PcG) genes act as transcriptional repressors to
      regulate A-P patterning by either directly or indirectly controlling the
      coordinated expression of the HOM/Hox homeobox (Curr. Opin. Genet. Dev. 7 (1997)
      488; Trends Genet. 13 (1997) 167). We describe the isolation and characterization
      of a novel mammalian PcG gene, termed Nervous System Polycomb-1 (NSPc1). Human
      and mouse NSPc1 genes encode proteins with an N-terminal RING finger domain and
      share homology with Drosophila melanogaster lethal(3)73Ah and the mammalian Mel18
      and Bmi1 genes. Transcripts are observed at 10 dpc in the otic vesicle,
      urogenital bud and dorsal root ganglia. At 11.5 dpc, transcripts are present in a
      subset of neural crest cell derivatives of the peripheral nervous system, and in
      the neural tube. NSPc1 expression is ubiquitous in adult tissue.

PMID- 11287197
TI  - Cloning and expression of a novel cysteine-rich secreted protein family member
      expressed in thyroid and pancreatic mesoderm within the chicken embryo.
AB  - We have isolated a new chicken gene that is a member of the cysteine-rich
      secreted protein family (CRISP). The CRISP family is composed of over 70 members
      that are found in many phyla of organisms, including: vertebrates, plants, fungi,
      yeast, and insects. Here we describe the cloning of a novel member of this
      family, SugarCrisp, and its expression pattern throughout chicken embryogenesis.
      We also describe its utility as a marker of thyroid and pancreatic mesoderm in
      the developing chicken embryo and its expression within the human and mouse in
      glandular tissue.

PMID- 11287198
TI  - Cloning and expression of CSAL2, a new member of the spalt gene family in chick.
AB  - In this study we describe cloning and expression of CSAL2, a second member of the
      spalt gene family in chick. All spalt proteins are characterized by the presence
      of multiple zinc-finger motifs, which are highly conserved. Mutations in HSAL1, a
      human spalt gene result in Townes-Brocks syndrome (TBS). We show here that CSAL2
      is expressed in many of the tissues affected in TBS, including neural tissue,
      limb buds, mesonephros and cloaca.

PMID- 11287199
TI  - Expression pattern of the frizzled 7 gene during zebrafish embryonic development.
AB  - We have identified a novel frizzled gene in zebrafish, (Danio rerio): frizzled 7,
      highly related to mouse, chick and Xenopus fz7. No maternal expression was
      detected. Zygotic transcription starts at the end of gastrulation anteriorly in
      the presumptive neurectoderm and in the presomitic mesoderm. During somitogenesis
      expression is detected in developing central nervous system, including forebrain,
      midbrain, hindbrain and spinal cord, the lateral mesoderm and the anterior part
      of the forming somites. The strong sequence conservation of fz7 to the mouse,
      chick and Xenopus counterparts is also true for their expression pattern.

PMID- 11287200
TI  - Dynamic expression of alternate splice forms of D-cbl during embryogenesis.
AB  - The Cbl family of proteins act as E3 ubiquitin-protein ligases and have been
      associated with the down regulation of a variety of receptor tyrosine kinases.
      Cbl proteins associate with many different cell signalling molecules suggesting
      that they may have functions outside of the RING finger-mediated ubiquitin ligase
      activity. The Drosophila melanogaster cbl gene (D-cbl) encodes two splice forms
      (Oncogene 19 (2000) 3299). Here we report on the differential expression of these
      isoforms during Drosophila embryogenesis. Both isoforms are maternally expressed
      but the long isoform of D-cbl is also transiently expressed in the invaginating
      mesoderm and later is specifically expressed in neurons of the central nervous
      system (CNS). Cbl protein is shown to be localised to axons of the longitudinal
      connectives and commissures in the central nervous system.

PMID- 11287202
TI  - Tissue-specific expression of an Ornithine decarboxylase paralogue, XODC2, in
      Xenopus laevis.
AB  - Ornithine decarboxylase (ODC) is involved in the biosynthesis of polyamines and
      hence has been found in almost all types of cells studied. Therefore it is
      frequently used as internal standard. We isolated a cDNA, XODC2, which is a
      paralogue to ubiquitous ODC and expressed in a spatial and temporal manner during
      the early embryogenesis of Xenopus laevis. Expression of XODC2was first detected
      at the animal pole at stage 9. During neurula stages the signals were found both
      in the extreme anterior and posterior part of the dorsal body axis. In tailbud
      stages the expression is further shifted to both the tail and head areas and
      gradually restricted to distinct tissues: forebrain, inner layer of epidermis of
      the head area, stomodeal-hypophyseal anlage, frontal gland, ear vesicle,
      branchial arches, the front tip of neural tube and proctodeum. In addition,
      signals were also found in the inner layer of epidermis underneath the cement
      gland during early tailbud stages while in later tailbud stages signals were
      detected at the apical zone of the cement gland. Comparative studies indeed could
      confirm that XODC1 in contrast to XODC2 is expressed ubiquitously throughout the
      whole embryos during early development of Xenopus laevis.

PMID- 11287201
TI  - Dystrophin and Dp71, two products of the DMD gene, show a different pattern of
      expression during embryonic development in zebrafish.
AB  - Dystrophin, the protein defective in Duchenne muscular dystrophy (DMD), plays a
      critical role in the formation and maintenance of the neuromuscular junction. In
      addition to dystrophin, activation of internal promoters of the DMD gene leads to
      the production of several short products. Among these, Dp71, which consists of
      the C-terminal domain of dystrophin, is the most abundant product of the gene in
      non-muscle tissues and brain. In this report, we compare the temporal and
      regional expression patterns of dystrophin and Dp71 at different stages of
      embryonic development and during retinal differentiation in zebrafish. The Dp71
      transcripts are the earliest to be expressed at 9-10 h post-fertilization (hpf)
      in the axial mesoderm. As development proceeds, intense Dp71 staining is observed
      in the notochord, the developing brain, the marginal regions of the somites and
      the eye primordium. At the completion of retinal differentiation, Dp71 is
      expressed in the ganglion and inner nuclear layers. Transcripts encoding
      dystrophin have a slightly later onset of expression, 13-14 hpf, and remain
      restricted to the transverse myosepta through all the developmental stages
      examined. The complementary patterns of expression of dystrophin and Dp71 suggest
      that these two proteins exert different functions during embryonic development in
      zebrafish.

PMID- 11287203
TI  - Cloning and developmental expression of a zebrafish meis2 homeobox gene.
AB  - We show here that a zebrafish meis2 gene homolog has a dynamic expression pattern
      in the developing mesoderm and central nervous system. Meis family homeodomain
      proteins are known to act as cofactors with other homeodomain proteins. We find
      expression of meis2.1 in the developing zebrafish hindbrain and somites,
      correlating with reported sites of zebrafish hox gene expression, as well as in
      presumptive cerebellum, midbrain, retina and ventral forebrain. The expression
      pattern shares some, but not all, features with that of murine Meis2.

PMID- 11287204
TI  - Xenopus brevican is expressed in the notochord and the brain during early
      embryogenesis.
AB  - A complete cDNA encoding the Xenopus laevis homologue of the aggrecan/versican
      family member, brevican (Xbcan) was cloned from an embryonic stage 42 cDNA
      library. In the deduced amino acid sequence, 1152 in length, similarity to the
      hyaluronan-binding (link) domains of brevicans from other species were present in
      the N-terminal region as well as EGF-, lectin- and complement regulatory protein
      like domains in the C-terminal part, the latter three being characteristic for
      brevican found within the extracellular matrix (J. Biol. Chem. 269 (1994) 10119).
      Indeed, Xbcan was secreted into the extracellular space as a soluble protein when
      expressed in oocytes. No cDNAs encoding a GPI-anchored bcan variant could be
      isolated from that cDNA library. During embryonic development, the expression of
      this gene was first observed in the notochord of neurula stage embryos. In
      addition to this, in tailbuds, Xbcan was also found to be expressed within the
      fifth and sixth rhombomere of the hindbrain. In tadpole stage embryos, expression
      was furthermore observed in periventricular regions of the developing brain and
      the rostral part of the spinal cord.

PMID- 11287205
TI  - Xpitx3: a member of the Rieg/Pitx gene family expressed during pituitary and lens
      formation in Xenopus laevis.
AB  - Xpitx3 is the Xenopus homologue of the mouse Pitx3 gene and belongs to the family
      of RIEG/PITX homeobox genes. Here, we report on the embryonic expression of
      Xpitx3. It is transcribed in the presumptive pituitary already at the open neural
      tube stage. During further development Xpitx3 is strongly transcribed in the
      pituitary Anlage, the lens placodes and head mesenchyme, respectively.

PMID- 11287206
TI  - Metallocarboxypeptidase Z is dynamically expressed in mouse development.
AB  - Metallocarboxypeptidase Z (CPZ), a new member of the regulatory
      metallocarboxypeptidases, contains a 120-residue cysteine-rich region that has 20
      35% amino acid sequence identity to Drosophila and mammalian frizzled proteins.
      In order to gain insights into the function of CPZ, we have examined the
      distribution of the protein by immunohistochemistry throughout mouse development.
      The expression of CPZ peaks at E9-E12, decreases in late gestation and falls
      further in adult tissues. CPZ expression in amnion cells, cochlear epithelial
      cells and surrounding mesenchyme, ventricular lining cells in the brain and
      cartilagenous condensations and surrounding connective tissue in ribs remains at
      high levels throughout mouse gestation. The expression pattern of CPZ overlaps
      with the expression pattern of several Wnt genes, consistent with the putative
      role of CPZ in Wnt signaling.

PMID- 11287207
TI  - Expression of proneural and neurogenic genes in the zebrafish lateral line
      primordium correlates with selection of hair cell fate in neuromasts.
AB  - Expression of a mouse atonal homologue, math1, defines cells with the potential
      to become sensory hair cells in the mouse inner ear (Science 284 (1999) 1837) and
      Notch signaling limits the number of cells that are permitted to adopt this fate
      (Nat. Genet. 21 (1999) 289; J. Neurocytol. 28 (1999) 809). Failure of lateral
      inhibition mediated by Notch signaling is associated with an overproduction of
      ear hair cells in the zebrafish mind bomb (mib) and deltaA mutants (Development
      125 (1998a) 4637; Development 126 (1999) 5669), suggesting a similar role for
      these genes in limiting the number of hair cells in the zebrafish ear. This study
      extends the analysis of proneural and neurogenic gene expression to the lateral
      line system, which detects movement via clusters of related sensory hair cells in
      specialized structures called neuromasts. We have compared the expression of a
      zebrafish atonal homologue, zath1, and neurogenic genes, deltaA, deltaB and
      notch3, in neuromasts and the posterior lateral line primordium (PLLP) of wild
      type and mib mutant embryos. We describe progressive restriction of proneural and
      neurogenic gene expression in the migrating PLLP that appears to correlate with
      selection of hair cell fate in maturing neuromasts. In mib mutants there is a
      failure to restrict expression of zath1 and Delta homologues in the neuromasts
      revealing similarities with the phenotype previously described in the ear.

PMID- 11287208
TI  - Expression of the Na-K-2Cl-cotransporter NKCC1 during mouse development.
AB  - Here we describe the expression pattern of the Na-K-2Cl-cotransporter NKKC1
      during embryonal and early postnatal mouse development. During early stages
      hybridization signals were detected over single cells of the developing
      neuroepithelia, whereas the neuroepithelium of the basal telencephalon was
      labeled continuously. With ongoing differentiation a distinct pattern of
      hybridization became apparent, which switched from a neuronal to a more glial
      pattern in the adult. Outside the nervous system NKCC1 transcripts were present
      in many organs and were mostly confined to epithelia.

PMID- 11287209
TI  - Ci-IPF1, the pancreatic homeodomain transcription factor, is expressed in neural
      cells of Ciona intestinalis larva.
AB  - We describe the cloning and the expression pattern of insulin promoter factor 1
      in the ascidian Ciona intestinalis (Ci-IPF1). Northern blot analysis showed that
      transcripts appeared at the late tailbud stage and increased at the larval stage.
      We have raised a specific antibody against the Ci-IPF1-GST fusion protein to
      determine the spatial expression of this gene. The protein is immunodetected at
      the larval stage in the sensory vesicle, in the visceral ganglion and in the
      mesenchymal cells. Our results support the hypothesis that IPF1/IDX1 might have
      extrapancreatic functions during animal development, particularly in neural
      cells.

PMID- 11287210
TI  - Xenopus p63 expression in early ectoderm and neurectoderm.
AB  - The tumor-suppressor protein p53 belongs to a small gene family that includes p63
      and p73. While p53 and p73 regulate cell cycle progression and apoptosis, the
      major role of p63 appears to be in promoting ectodermal proliferation and
      differentiation. In this report we describe the cloning of a Xenopus orthologue
      of mammalian p63 that is extraordinarily conserved in sequence. The major sites
      of expression of Xenopus p63 mRNA are the epidermis and some neural crest and
      crest derivatives such as the branchial arches and tail fin. Expression is also
      observed in the neural plate and in the stomodeal-hypophyseal anlage. Antibodies
      against p63 detect a nuclear protein that is distributed in a manner similar to
      that of Xp63 mRNA. Both mRNA and protein are conspicuously absent from regions of
      the epidermal sensorial layer that are induced to form a number of (but not all)
      ectodermal placodes and Xp63 protein levels are particularly dynamic in the
      epidermis of the eye as the lens forms.

PMID- 11287211
TI  - Chicken Nkx6.1 expression at advanced stages of development identifies distinct
      brain nuclei derived from the basal plate.
AB  - This study of the embryonic chicken central nervous system defines previously
      unknown domains of neuroepithelial Nkx6.1 expression in neuroepithelial
      progenitors and identifies nuclei that express Nkx6.1 at progressively more
      advanced stages of central nervous system development.

PMID- 11287212
TI  - Quantitative expression studies of aldolase A, B and C genes in developing
      embryos and adult tissues of Xenopus laevis.
AB  - We previously cloned cDNAs for all the members (A, B and C) of Xenopus aldolase
      gene family, and using in vitro transcribed RNAs as references, performed
      quantitative studies of the expression of three aldolase mRNAs in embryos and
      adult tissues. A Xenopus egg contains ca. 60 pg aldolase A mRNA and ca. 45 pg
      aldolase C mRNA, but contains only ca. 1.5 pg aldolase B mRNA. The percent
      composition of three aldolase mRNAs (A:B:C) changes from 56:1.5:42.5 (fertilized
      egg) to 54:10:36 (gastrula), to 71:14.5:14.5 (neurula) and to 73:20:7 (tadpole)
      during development. These results are compatible with the previous results of
      zymogram analysis that aldolases A and C are the major aldolases in early
      embryos, whose development proceeds depending on yolk as the only energy source.
      Aldolase B mRNA is expressed only late in development in tissues such as
      pronephros, liver rudiment and proctodeum which are necessary for the future
      dietary fructose metabolism, and the expression pattern is consistent to that in
      adult tissues. We also show that three aldolase genes are localized on different
      chromosomes as single copy genes.

PMID- 11287213
TI  - Protein- and tryptophan-restricted diets induce changes in rat gonadal hormone
      levels.
AB  - The release of gonadotrophic hormones starts at puberty and, along with the
      subsequent estral cyclicity, is subject to hormonal feedback systems and to the
      action of diverse neuroactive substances such as gamma amino butyric acid and
      catecholamines. This study shows the effect of the administration during 40 days
      of protein-restricted and corn-based (tryptophan- and lysine-deficient) diets on
      the serotonin concentration in medial hypothalamic fragments as well as in
      follicle-stimulating luteinizing hormones, 17-beta-estradiol and progesterone
      serum levels, and estral cyclicity in 60- and 100-day-old rats (young, mature,
      and in gestation). In young rats, a delay in vaginal aperture development, and a
      lengthening of the estral cycle to a continuous anestral state was observed,
      mainly in the group fed corn. This group showed a 25% decrease in the serotonin
      concentration compared with the protein-restricted group, which exhibited an
      increase of 9% over the control group. Luteinizing hormone levels decreased in
      16% and 13%, whereas follicle-stimulating hormone increased in 13% and 5% in the
      young animals of restricted groups, respectively, compared with the control
      group. Serum progesterone levels decreased only in young restricted versus
      control animals, and no differences were seen among adult and gestational rats.
      Serum levels of 17-beta-estradiol in restricted animals showed different
      concentration patterns, mainly in the corn group, which was higher at the 20th
      gestational day, falling drastically postpartum. The results obtained in this
      study show serotonin to be a very important factor in the release of
      gonadotrophic hormones and the start of puberty.

PMID- 11287214
TI  - Transfer of cobalamin from intrinsic factor to transcobalamin II.
AB  - The process is obscure by which cobalamin (Cbl) in the endocytosed intrinsic
      factor (IF)-cobalamin (Cbl) complex is released and transferred to transcobalamin
      II (TCII) within the enterocyte. Using recombinant IF and TCII, binding of Cbl to
      IF at pH 5.0 was 70% of binding at pH 7.0, whereas for TCII alone, the value was
      only 12%. TCII binding activity was lost rapidly at lower pH, but this was not
      due to protease action. TCII incubated at pH 5.0 with cathepsin L was degraded
      and could not subsequently bind Cbl. Thus, transfer from IF to TCII is unlikely
      to occur within an acid compartment. Only 13-15% of bound Cbl was released at pH
      5.0 and pH 6.0 from either rat IF, human IF, or human TCII. The K(a) of human or
      rat IF at pH 7.5 was 2.2 nM; for TCII, the value was 0.34 nM. At pH 7.5, Cbl
      transfers from IF to TCII, but only to a limited extent (21%), as detected by
      nondenaturing electrophoresis. Transfer of Cbl from IF to TCII could not be
      demonstrated at pH values of 5.0 or 6.0. Thus, luminal transfer of Cbl between IF
      and TCII is likely to be limited, but is possible. The most likely mechanism for
      intracellular transfer of Cbl from IF to TCII involves initial lysosomal
      proteolysis of IF, with subsequent Cbl binding to TCII in a more neutral cellular
      compartment.

PMID- 11287215
TI  - Dietary fatty acids effects on sucrose-induced cardiovascular syndrome in rats.
AB  - Cardiovascular disease is one of the leading causes of morbidity and mortality in
      Mexico. We investigated the effects of omega-3 (n-3) and omega-6 (n-6)
      polyunsaturated fatty acids on the metabolic syndrome associated with
      cardiovascular disease in a high-sucrose-fed rat model. The metabolic syndrome
      induced rats showed a significant increase in systolic blood pressure, serum
      insulin, nonfasting serum triglyceride and serum cholesterol levels. Experimental
      high-sucrose-fed animals received either a n-3 or n-6 enriched diet or a control
      diet during 6 weeks. Animals fed the n-3 enriched diet had a significant
      reduction in blood pressure and serum insulin and triglyceride levels. Serum
      triglyceride levels were also significantly reduced in the n-6-rich diet animals.

PMID- 11287216
TI  - Diet- and diabetes-induced change in insulin binding to the nuclear membrane in
      spontaneously diabetic rats is associated with change in the fatty acid
      composition of phosphatidylinositol.
AB  - Insulin binding to the nucleus in vivo alters the binding of transcription
      factors to the promoter region of lipogenic genes, thereby changing expression of
      these genes. The present research was designed to investigate whether change in
      diet fat composition alters insulin binding to nuclear insulin receptors at
      various stages of onset of diabetes in spontaneously diabetic B/B rats. The fatty
      acid composition of lipids comprising the nuclear membrane was also examined.
      Weanling rats were fed a nonpurified diet (low-fat commercial rat chow) or a
      semipurified diet containing 20 g/100 g fat of either high (1.0) or low (0.25)
      polyunsaturated to saturated (P/S) fatty acid ratio. Insulin binding to liver
      nuclei was measured when the blood glucose level was 100 mg/dl and 400 mg/dl. No
      effect of diet treatment on age of onset of diabetes was found. Specific binding
      of insulin to nuclei from rats with a blood glucose level of 100 mg/dl did not
      differ from nondiabetic rats, and was higher than in diabetic rats with a blood
      glucose level of 400 mg/dl. Insulin binding was greater in rats fed a high P/S
      diet. The high versus low P/S diet treatment primarily altered the fatty acid
      composition of phosphatidylinositol in the nuclear membrane. Diabetic rats fed
      nonpurified diet showed a significant increase in levels of 18:2(n-6) and 22:6(n
      3), whereas 20:4(n-6) decreased in the phosphatidylcholine fraction compared with
      control rats fed chow. As rats became diabetic, the level of monounsaturated
      fatty acids, 18:2(n-6) and 22:6(n-3) decreased, whereas the level of 20:4(n-6)
      increased in phosphatidylinositol. Change in the composition of these nuclear
      membrane components may be associated with transitions in insulin binding.

PMID- 11287217
TI  - Hydrolysis of tocopheryl and retinyl esters by porcine carboxyl ester hydrolase
      is affected by their carboxylate moiety and bile acids.
AB  - The objective of this study was to examine the in vitro hydrolysis of vitamin E
      esters (alpha-tocopheryl acetate, alpha-tocopheryl succinate and alpha-tocopheryl
      nicotinate) by pancreatic carboxyl ester hydrolase (CEH) at the concurrent
      presence of different bile acids at different concentrations. The assay was
      performed by measuring the amount of alpha-tocopherol released by porcine
      pancreatic juice upon addition to different solutions of alpha-tocopheryl esters,
      which were dispersed in bile acid mixed micelles at 37 degrees C, pH 7.4. The CEH
      activity was 10 U in the final assay, and the optimal concentration of cholate in
      this in vitro-system was determined to 30 mM for the hydrolysis of alpha
      tocopheryl acetate. The hydrolysis of alpha-tocopheryl esters required presence
      of pancreatic juice and bile acids, and the results showed furthermore that the
      ability of pancreatic CEH towards hydrolysis of different alpha-tocopheryl esters
      increased with increasing lipophility, irrespective of the type or concentration
      of bile acid present in the assay. Likewise, retinyl palmitate was hydrolyzed at
      a faster rate than retinyl acetate. The structure of the bile acid influenced the
      rate of hydrolysis. Thus, cholate followed by glycodeoxy- and
      glycochenodeoxycholate were the most effective activators of CEH among the bile
      acids tested in this assay. The presence of gamma-tocopherol or all-trans-retinyl
      acetate in the assay showed a non-competitive inhibition of the hydrolysis rate
      of alpha-tocopheryl acetate.

PMID- 11287218
TI  - Idiorrhythmic zinc dose-rate induction of intestinal metallothionein in rats
      depends upon their nutritional zinc status(dagger).
AB  - The idiorrhythmic dose-rate feeding experimental model was used to study the
      induction of intestinal metallothionein (iMT) by zinc (Zn) in the
      gastrointestinal (GIT) mucosa of young growing male rats relative to their
      nutritional Zn status. The idiorrhythmic approach requires that the average
      dietary Zn concentration, referred to as modulo (M), is kept constant across
      different groups over the whole experimental epoch (E). This is done by adjusting
      the Zn concentration of the supplemented diet to compensate for the reduction in
      the number of days on which this diet is fed, the latter being spread evenly over
      the whole experiment. Idiorrhythms (I) involve offering the diet with n times the
      overall Zn concentration (M) only every nth day with a Zn-deficient diet offered
      on other days. We studied three modulos (low-Zn, M3; adequate-Zn, M12; and high
      Zn, M48), each M having 8 analogous idiorrhythms (I = Mx/1 to 8Mx/8); every I was
      fed over a 48-d idiorrhythmic E. Over the wide range of peak doses of dietary Zn
      (3-384 mg Zn/kg diet), the higher the modulo, the greater the capacity for iMT to
      be induced (M3 < M12 < M48; P < 0.05). Also, the ability of Zn to induce iMT
      increased proportionally with the progression of the idiorrhythms from I = Mx/1
      to 8Mx/8 (P < 0.001). When rats were fed M3, less Zn was required to induce iMT
      than when they were fed M12 or M48. Thus, within the M and E limits of this
      study, the better the nutritional Zn status of the animal, the more Zn is
      required to induce iMT and vice versa. The fact that iMT was increased means that
      the amount of available Zn was not proportional with the actual steady state of
      its metabolism. This indicates that for any Zn supplementation program to be
      effective, it should progress gradually from a lower to a higher Zn dose relative
      to the given nutritional Zn status.

PMID- 11287219
TI  - Fructose triggers DNA modification and damage in an Escherichia coli plasmid.
AB  - The nonenzymatic reaction between reducing sugars and amino groups of long-lived
      macromolecules results in an array of chemical modifications that may account for
      several physiological complications. The characteristics of the reaction are
      directly related to the type of the reducing sugars involved, whether aldoses or
      ketoses, phosphorylated or non-phosphorylated, and these in turn determine the
      consequences of the induced modifications. So far, most studies have been focused
      on the nonenzymatic reaction between glucose and proteins, while the reaction
      with fructose, a faster glycating agent, attracted only a minor attention. We
      have recently demonstrated that long-term fructose consumption induces age
      related changes in collagen from skin and cortical bones faster than glucose. In
      the present study we provide evidence that fructose and its phosphate metabolites
      can modify DNA faster than glucose and its phosphate metabolites under in vitro
      conditions. Incubating the plasmid pBR322 with fructose and glucose phosphate
      metabolites induced DNA modifications and damage that were verified by gel
      electrophoresis and transformation capacity of the plasmid into an Escherichia
      coli host. The intensity of the tested sugars to modified and damage DNA after
      incubation for 15 days increased significantly in the following order: glucose 1
      phosphate < glucose < glucose 6-phosphate < fructose 1-phosphate < fructose <
      fructose 6-phosphate. The data suggest that fructose should deserve more
      attention as a factor that may influence glycation and induce physiological
      complications.

PMID- 11287220
TI  - Effect of various levels of supplementation with sodium pivalate on tissue
      carnitine concentrations and urinary excretion of carnitine in the rat.
AB  - In previous studies, sodium pivalate has been administered to rats in their
      drinking water (20 mmoles/L; equivalent to 0.3% of the diet) as a way to lower
      the concentration of carnitine in tissues and to produce a model of secondary
      carnitine deficiency. Although this level of supplementation results in a marked
      decrease in carnitine concentration in a variety of tissues, it does not produce
      the classical signs of carnitine deficiency (i.e., decreased fatty acid oxidation
      and ketogenesis). The present study was designed (1) to determine if increasing
      the level of pivalate supplementation (0.6, 1.0% of the diet) would further
      reduce the concentrations of total and free carnitine in rat tissues without
      altering growth or food intake, and (2) to examine the effect of length of
      feeding (4 vs. 8 weeks) on these variables. Male, Sprague-Dawley rats were
      randomly assigned to either a control (0.2% sodium bicarbonate) or experimental
      diet (0.3, 0.6, 1.0% sodium pivalate) for either four or eight weeks. Animals (n
      = 6/group) were housed in metabolic cages; food and water were provided ad
      libitum throughout the study. Supplementation with sodium pivalate did not alter
      water intake or urine output. Ingestion of a diet containing 1.0% pivalic acid
      decreased food intake (g/day; P < 0.05), final body weight (P < 0.007), and
      growth rate (P < 0.001) after four weeks. The concentration of total carnitine in
      plasma, heart, liver, muscle, and kidney was reduced in all experimental groups
      (P < 0.001), regardless of level of supplementation or length of feeding. The
      concentration of free carnitine in heart, muscle, and kidney was also reduced (P
      < 0.001) in rats treated with pivalate for either four or eight weeks. The
      concentration of free carnitine in liver was reduced in animals supplemented with
      pivalate for eight weeks (P < 0.05), but no effect was observed in livers from
      rats treated for four weeks. Excretion of total carnitine and short chain
      acylcarnitine in urine was increased in pivalate supplemented rats throughout the
      entire feeding period (P < 0.001). Free carnitine excretion was increased during
      Weeks 1 and 2 (P < 0.01), but began to decline during Week 3 in experimental
      groups. During Weeks 6 and 8, free carnitine excretion in pivalate supplemented
      rats was less than that of control animals (P < 0.01). In summary, no further
      reduction in tissue carnitine concentration was observed when rats were
      supplemented with sodium pivalate at levels greater than 0.3% of the diet. Food
      intake (g/day) and growth were decreased in rats fed a diet containing 1.0%
      sodium pivalate. These data indicate that maximal lowering of tissue carnitine
      concentrations is achieved by feeding diets containing 0.3% sodium pivalate or
      less.

PMID- 11287223
TI  - Plant biotechnology Light at the end of the tunnel: from genes to function.

PMID- 11287224
TI  - Computational methods for gene annotation: the Arabidopsis genome.
AB  - Since the structure of the DNA molecule was identified half a century ago, the
      complete genome sequence has been determined for 37 prokaryotes and several
      eukaryotes. With the exponential growth of genetic information, bioinformatics
      has attempted to predict gene locations and functions in cyberspace prior to
      experimental confirmation at the bench.

PMID- 11287225
TI  - Analysis of the plant proteome.
AB  - For many years the analysis of plant proteomes has been restricted to the
      construction of descriptive catalogues or the search for markers. The analysis of
      plant proteomes is now gaining a functional dimension, however, because the focus
      has shifted onto well-defined plant-specific tissues and organelles, the
      simultaneous mining of proteomic and physiological data and specific
      methodological efforts.

PMID- 11287226
TI  - Gene discovery via metabolic profiling.
AB  - Biochemical analysis is adding a new dimension to the process of gene discovery.
      Two major developments have recently taken place in the emerging science of
      biochemical genomics. The first is an approach that uses a combination of tagged
      fusion proteins and simple pooling strategies in order to efficiently and
      directly assign biochemical function to the products of open reading frames
      (ORFs) expressed in yeast. The second is the application of metabolic profiling
      technologies to the study of mutant and transgenic plants. The latter approach
      has the potential not only to discover novel genes but also to ascribe a function
      to them in the context of the organism from which they are derived.

PMID- 11287227
TI  - Elimination of selection markers from transgenic plants.
AB  - Selection markers, which were necessary for the isolation of transgenic plants,
      are no longer required in mature plants, especially when they are grown in
      fields. Regimes to achieve their efficient elimination, mostly through site
      specific recombination or transposition, are being developed.

PMID- 11287228
TI  - Novel approach in plastid transformation.
AB  - Engineering the nuclear genome of plants is perceived to be associated with
      problems regarding biosafety and the stability of expression of the transgene.
      Alternative transformation strategies using the genomic outfit of the plastid
      promise to be more successful in this respect. Over the past few years progress
      has been made in screening procedures, and plastid transformation technology has
      allowed function to be assigned to open reading frames, massive expression of
      insecticidal agents and proteins involved in herbicide resistance, and the
      accumulation of biopolymers. Recently, the design of a novel femtoinjection
      technique that allows injection into chloroplasts has provided the opportunity to
      further manipulate and understand chloroplastic gene expression.

PMID- 11287229
TI  - Viral suppressors of RNA silencing.
AB  - The suppression of RNA silencing by plant viruses represents a viral adaptation
      to a novel host antiviral defense. Three types of viral suppressors have been
      identified through the use of a variety of silencing suppression assays. The
      first two types of suppressor are capable of a complete or partial reversal of
      pre-existing RNA silencing; the third type does not reverse RNA silencing but can
      instead prevent its systemic signaling.

PMID- 11287230
TI  - Metabolic engineering and applications of flavonoids.
AB  - During the past decade, the increasing knowledge of flavonoid biosynthesis and
      the important function of flavonoid compounds in plants and in human and animal
      nutrition have made the biosynthetic pathways to flavonoids and isoflavonoids
      excellent targets for metabolic engineering. Recent strategies have included
      introducing novel structural or regulatory genes, and the antisense or sense
      suppression of genes in these pathways.

PMID- 11287231
TI  - Plant concepts for mineral acquisition and allocation.
AB  - Plant biotechnology is expected to make a major contribution to the steady
      increase of crop production in the near future. The improvement of mineral
      assimilation has to meet the challenges of reducing fertilizer application in
      developed countries, preserving the environment, enabling sustainable agriculture
      management and generating low-input crops with increased performance in areas
      where soil infertility limits productivity. Natural genetic resources and
      engineered plants will help to achieve the implementation of traits for improved
      mineral assimilation.

PMID- 11287232
TI  - Oligonucleotide-directed plant gene targeting.

PMID- 11287233
TI  - Biochemical engineering: Bioprocessing of therapeutic proteins.

PMID- 11287234
TI  - Understanding and modulating apoptosis in industrial cell culture.
AB  - Currently, the production of therapeutic recombinant proteins relies heavily on
      the large-scale culture of eukaryotic cells that secrete the protein of interest
      into the media. It has been recognized that programmed cell death, or apoptosis,
      may pose a significant hurdle to maximum productivity in such systems. With a
      greater understanding of the molecular events causing apoptosis, alterations can
      be made to the cells and culture conditions to prevent apoptosis and enhance
      volumetric productivity.

PMID- 11287235
TI  - Industrial choices for protein production by large-scale cell culture.
AB  - Traditional barriers to large-scale mammalian culture have now been addressed,
      with the standard stirred-tank reactor emerging as industry's technology of
      choice. The issues of adapting cells to suspension culture, shear sensitivity and
      oxygen supply have been largely resolved. But for many low-volume and specialty
      applications, such as the production of viral vaccines and gene therapies,
      reactor technology remains diversified, with reactor types ranging from roller
      bottles to stacked plates and hollow fibers.

PMID- 11287236
TI  - Therapeutic antibody expression technology.
AB  - With the technological advances made during the past decade, antibodies now
      represent an important and growing class of biotherapeutics. With the potential
      new targets resulting from genomics and with methods now in place to make fully
      human antibodies, the potential of antibodies as valuable therapeutics in
      oncology, inflammation and cardiovascular disease can be fully realised. Systems
      to produce these antibodies as full-length molecules and as fragments include
      expression in both mammalian and bacterial cells grown in bioreactors and in
      transgenic organisms. Factors including molecular fidelity and the cost of goods
      are critical in evaluating expression systems. Mammalian cell culture and
      transgenic organisms show the greatest promise for the expression of full-length,
      recombinant human antibodies, and bacterial fermentation seems most favorable for
      the expression of antibody fragments.

PMID- 11287237
TI  - Advances in Escherichia coli production of therapeutic proteins.
AB  - Escherichia coli offers a means for the rapid and economical production of
      recombinant proteins. These advantages, coupled with a wealth of biochemical and
      genetic knowledge, have enabled the production of such economically sensitive
      products as insulin and bovine growth hormone. Although significant progress has
      been made in transcription, translation and secretion, one of the major
      challenges is obtaining the product in a soluble and bioactive form. Recent
      progress in oxidative cytoplasmic folding and cell-free protein synthesis offers
      attractive alternatives to standard expression methods.

PMID- 11287238
TI  - Protein refolding for industrial processes.
AB  - Inclusion body refolding processes are poised to play a major role in the
      production of recombinant proteins. Improving renaturation yields by minimizing
      aggregation and reducing chemical costs are key to the industrial implementation
      of these processes. Recent developments include solubilization methods that do
      not rely on high denaturant concentrations and the use of high hydrostatic
      pressure for simultaneous solubilization and renaturation.

PMID- 11287239
TI  - Membrane separations in biotechnology.
AB  - Membranes have always been an integral part of biotechnology processes. The
      sterile filtration of fermentation media, purification buffers, and protein
      product pools is standard practice in industry. Microfiltration is also used
      extensively for medium exchange and harvest. Ultrafiltration can be found in
      virtually every biotechnology process. A significant number of mammalian cell
      processes use filtration as an integral part of the overall strategy for viral
      clearance. Depth filters have also seen widespread use for the clarification of
      both mammalian and bacterial feed streams. Improvements in membrane technology
      are now focused on high-resolution applications, including improved protein-virus
      separation, protein purification by high-performance tangential flow filtration
      and enhanced membrane chromatography. These developments will allow membranes to
      play an important role in the evolution of the next generation of biotechnology
      processes.

PMID- 11287240
TI  - Emerging protein delivery methods.
AB  - The efficient and safe delivery of therapeutic proteins is the key to commercial
      success and, in some cases, the demonstration of efficacy in current and future
      biotechnology products. Numerous delivery technologies and companies have evolved
      over the past year. To critically evaluate the available options, each method
      must be assessed in terms of how easily it can be manufactured, impact on protein
      quality, bioavailability, and toxicity. Recent advances in depot delivery systems
      have, for the most part, overcome all of these obstacles except for complex and
      costly manufacturing. On the other hand, pulmonary delivery usually involves
      efficient manufacturing, but low protein bioavailability resulting in higher
      doses compared with injections. Although recent advances in transdermal and oral
      delivery have been significant, both of these delivery routes require logarithmic
      increases in bioavailability to make them viable candidates for
      commercialization. In the next few years, protein delivery for commercial
      products will probably be limited to injection devices, depot systems and
      pulmonary administration.

PMID- 11287241
TI  - International Adolescent Health: realizing his vision: Herbert Friedman, Ph.D.
      (1936-2000).

PMID- 11287242
TI  - Role of self-presentation in the health practices of a sample of Irish
      adolescents.
AB  - The association between self-presentational motives and health behaviors were
      studied in a sample of 183 Irish adolescents. Among girls, dieters and
      nonexercisers scored higher on measures of trait self-presentational concern than
      nondieters and exercisers. Self-presentational concerns were positively
      correlated with boys' and girls' endorsement of self-presentational motives for
      certain health practices.

PMID- 11287243
TI  - Outcomes of a brief alcohol abuse prevention program for Israeli high school
      students.
AB  - PURPOSE: To implement a brief intervention aimed at reducing abuse of alcohol
      among adolescents, and to assess its effectiveness. METHODS: One thousand 10th
      grade students from seven high schools, chosen by random from the roster of all
      schools in southern Israel, were assigned to intervention and control groups. The
      intervention, which was based on Botvin's social skills theory, was conducted
      over 3 days and included dissemination of information, workshops, lectures by
      guest experts, and activity areas. It was administered by the staff of the high
      schools and the Psychological Counseling Service in Israel. A self-administered
      questionnaire was answered anonymously by students in the 10th grade (pretest)
      and again in the 11th and 12th grades (posttests). It included questions on
      sociodemographic data, alcohol-related habits, smoking habits, use of illicit
      drugs, knowledge, and attitudes. Data were collected between 1994 and 1997 with a
      76% follow-up rate at 2 years. RESULTS: At baseline there was no statistical
      difference in alcohol consumption between the intervention and control groups. At
      1- and 2-year follow-up the rates of alcohol consumption did not change in the
      intervention group (p > .05) but rose significantly in the control group (p <
      .001). In multiple regression analysis the variables male gender, positive
      attitudes, cigarette smoking, availability of illegal drugs, and intervention
      group were significant predictors of alcohol consumption. CONCLUSIONS: The
      results of this study show the effectiveness of this intervention program, based
      on reduced alcohol consumption in the intervention group at 1- and 2-year follow
      up, compared with the control group. Compared with other programs, the present
      intervention is brief, intensive, and relatively easy to implement.

PMID- 11287244
TI  - Heavy drinking is associated with more severe psychosocial dysfunction among
      girls than boys in Finland.
AB  - PURPOSE: To investigate social, psychological, and environmental factors related
      to heavy drinking by 15-year-old Finnish school pupils. METHODS: Each of 240
      pupils completed a questionnaire about alcohol use, smoking, and illicit drug
      use; an Offer Self-Image Questionnaire; an Inventory of Parent and Peer
      Attachment; and a Psychosomatic Symptoms Questionnaire. Teachers assessed each
      pupil according to a Social Skills Rating Scale. Academic achievement was
      assessed on the basis of report grades. RESULTS: Heavy drinking was associated
      with smoking, trial of drugs, poor social skills in class, and poor school
      achievement in both boys and girls. In girls, heavy drinking was associated with
      psychosomatic symptoms and a negative social self-image. Girls who drank heavily
      also had more difficulty with concentration and externalizing problems and more
      problems with teachers than those who were abstinent or consumed alcohol
      moderately. The self-images of boys who drank heavily were more negative than
      those of alcohol-abstinent boys. In boys, heavy drinking was associated with
      higher numbers of peer relationships. CONCLUSIONS: Heavy drinking is associated
      with more severe psychosocial dysfunction among girls than boys. It may be
      possible to identify girls at school who drink heavily and guide them toward
      treatment.

PMID- 11287245
TI  - Use of health services and reported satisfaction among primary school adolescents
      in Arusha, Tanzania.
AB  - PURPOSE: To describe Tanzanian adolescents' utilization of health services, their
      satisfaction with the health services, and determinants of their satisfaction
      with these services. METHODS: A questionnaire was administered to 1279 seventh
      grade school pupils, measuring use of health services in the past 2 years,
      reasons for seeking health services, and satisfaction with the health services
      provided during the last visit. Descriptive statistics were calculated on health
      service utilization and satisfaction variables, and univariate and multiple
      logistic regression analyses were performed to assess the factors associated with
      reported satisfaction with the health services. RESULTS: Seventy-five percent of
      the respondents reported using modern health services only, 1.2% used traditional
      services only, and 10% had used both during the past 2 years. Fever was the most
      common reason for seeking modern health services, followed by injury. The vast
      majority of the respondents reported being satisfied with the services provided
      during the last visit. Age was the only factor significantly associated with
      being very satisfied with traditional health services, whereas type of health
      facility and discussion of the issues of sexually transmitted diseases and AIDS
      were significantly associated with being very satisfied with modern health
      services during the last visit. CONCLUSION: Urban primary school adolescents
      report using modern health services, and the majority are satisfied with the
      services.

PMID- 11287246
TI  - Health-related quality of life reported by French adolescents: a predictive
      approach of health status?
AB  - PURPOSE: To examine the relevance of a self-administered multidimensional
      instrument to the discrimination of illness and health among adolescents in South
      eastern France. METHODS: We show the results of a self-reported HRQL assessment
      by the Vecu et Sante Percue de l'Adolescent (VSP-A) multidimensional
      questionnaire, conducted on a population of 3061 adolescents. The VSP-A produces
      a score for each of the seven dimensions (relationships with friends,
      relationships with parents, school life, inaction, psychological distress,
      future, and energy/vitality) and a global score. The result is compared with the
      answers of the parents to the same multidimensional HRQL questionnaire reworded
      for them (VSP-P) and to the perceived health self-reported by the adolescents on
      a visual analogue scale (VAS). The adolescents filled both the VSP-A and VAS
      questionnaires twice at a 1-month interval. RESULTS: A total of 2941 adolescents
      completed the questionnaire correctly, and 1760 VSP-P questionnaires were filled
      out by their parents. The global HRQL score as well as the dimension scores from
      the parents' assessment were significantly different from those of the
      adolescents. At the inception, using three approaches (self-reported VAS, VSP-A,
      and VSP-P), it was possible to discriminate between ill and healthy adolescents.
      Nevertheless, the VSP-A completed at the inception is the only of the three
      approaches that can point out the adolescents who will become ill during the
      following month. Furthermore, the results reported by VSP-A largely agree with
      literature. CONCLUSION: The VSP-A could provide a comprehensive approach of HRQL
      of young people in both health prevention and the health care system.

PMID- 11287247
TI  - Health risk behaviors and associated risk and protective factors among Brazilian
      adolescents in Santos, Brazil.
AB  - OBJECTIVE: To describe the prevalence of health risk behaviors and identify risk
      and protective factors that are associated with several health risk behaviors
      (cigarette smoking, drug use, onset of sexual intercourse before age 15,
      pregnancy, gun-carrying, suicidal ideation, and suicide attempts) among
      adolescents in Brazil, as well as to explore gender differences. METHODS: We
      estimated prevalence rates, evaluated bivariate associations, and explored
      multivariate analyses using logistic regression on data from a 1997 survey of
      adolescent health among 2059 eighth- and 10(th)-grade students in Santos, Brazil.
      RESULTS: Youth in Santos, Brazil report high rates of gun-carrying, suicidal
      thoughts and attempts, sexual intercourse, and pregnancy. Factors associated with
      diminished involvement for nearly all health risk behaviors, for both boys and
      girls, included having good family relationships, and feeling liked by friends
      and teachers. Factors associated with increases in nearly all health risk
      behaviors were: gun-carrying and gun availability in the home, drug use, and
      sexual abuse. CONCLUSIONS: Factors that are associated with a wide range of
      health risk behaviors among adolescents in Brazil appear to parallel those found
      in industrialized countries: access to guns, substance use, and sexual abuse.
      Likewise, connectedness to family, school, and peers is consistently the
      protective factor associated with diminished risky behaviors.

PMID- 11287248
TI  - Adolescent maternal mortality in Mozambique.
AB  - PURPOSE: To describe adolescent maternal mortality and analyze its avoidability.
      METHODS: An audit approach was used to clarify the presence of avoidable factors
      in 239 maternal deaths, of which 22% were among adolescents. RESULTS: The main
      causes of adolescent death were malaria, pregnancy-induced hypertension,
      puerperal sepsis, and septic abortion. The audit classified as avoidable 75% of
      all maternal deaths. CONCLUSION: Adequate strategies addressing the special needs
      of adolescents are required to prevent currently high levels of maternal
      mortality in this age group.

PMID- 11287249
TI  - Family and adolescent childbearing.
AB  - PURPOSE: To determine the risk factors for adolescent childbearing in Taiwan
      within the context of family. METHODS: In this case-control study, the cases were
      198 mothers aged < or =19 years with firstborn infants in Taichung City, Taiwan,
      in 1997. The controls were composed of nonchildbearing adolescents matched with
      the cases with respect to age and neighborhood for each case. A self-administered
      structured questionnaire asking about a variety of family factors was used to
      gather relevant information from the study subjects. Adjusted odds ratios (ORs)
      with 95% confidence intervals (CIs) for variables associated with adolescent
      childbearing were obtained by multiple logistic regression analysis. RESULTS:
      There were 162 cases and the same number of controls completing the
      questionnaire, for a response rate of 81.8%. Compared with the controls,
      childbearing adolescents were more likely to have all adverse sociodemographic
      and familial conditions. However, multiple logistic regression analysis showed
      that adolescents living outside the home (adjusted OR = 2.1, 95% CI 1.0-4.6),
      single-parent families (adjusted OR = 4.8, 95% CI 1.4-16.1), family dysfunction
      (adjusted OR = 1.8, 95% CI 1.1-3.1), mother's inadequate education (adjusted OR =
      1.4, 95% CI 1.0-2.2), and mother's childbearing in adolescence (adjusted OR =
      4.9, 95% CI 2.2-11.0) were the significant risk factors for adolescent
      childbearing. CONCLUSIONS: Some familial factors contribute significantly to
      adolescent childbearing in Taiwan, as reported in other countries; these factors
      should be taken into consideration for further research and development of
      prevention programs.

PMID- 11287250
TI  - Swedish teenagers' attitudes toward the emergency contraceptive pill.
AB  - PURPOSE: To explore knowledge, attitudes toward, and experience with, the
      emergency contraceptive pill (ECP) among teenagers in Sweden. METHODS: A
      questionnaire with 23 questions concerning the students' demographics, knowledge
      of, attitudes toward, and experience of the ECP was delivered to a random sample
      of 20 classes in senior high school in two medium-sized cities in Sweden. The
      participation rate was 100% (n = 408). Differences in responses between teenagers
      in the two cities, boys and girls, theoretical and practical classes, or native
      Swedish and immigrant teenagers were calculated with the Chi-square test.
      RESULTS: The mean age was 16.5 years. Almost half (45.4%) of the teenagers had
      had sexual intercourse and of those, 28.3% stated that they themselves or their
      partner had used ECP. Four of five teenagers knew about ECP and where to obtain
      it if necessary. Many teenagers (67.3%) also knew that ECP prevented
      implantation. The main sources of information about ECP were youth clinics (n =
      179) and friends (n = 159). The attitude toward using ECP in an emergency
      situation was positive, but the teenagers, especially girls, were restrictive as
      to whether ECP should be available without a prescription. The girls believed ECP
      could be used much more, and two-thirds of both sexes thought it could lead to
      negligence with ongoing contraception. Seventy-seven percent of teenagers
      preferred turning to a youth clinic when in need of ECP. One in four believed
      that concerns for side effects could deter them from using ECP. CONCLUSIONS:
      Based on the results in the present study, the importance of counseling in this
      situation is confirmed. The awareness about ECP was good, but teenagers also
      expressed concerns about side effects. The girls were more hesitant than the boys
      about having ECP available over the counter.

PMID- 11287251
TI  - Assessment of physical activity among rural Senegalese adolescent girls:
      influence of age, sexual maturation, and body composition.
AB  - PURPOSE: To analyze the level of habitual physical activity and its relationship
      with age, maturational stage, and growth status in a group of adolescent
      Senegalese girls. METHODS: Physical activity was assessed for 3 consecutive years
      in a sample of 40 girls of rural origin. They were 13.3 +/- 0.5 years old at the
      beginning of the study and belonged to a Sereer community located in the center
      of Senegal. Minute-by-minute movement counts using accelerometers enabled
      quantification of levels of physical activity. The assessment was performed
      during a 4-day period in the first round (1997) and during a 3-day period in 1998
      and 1999. Half of the girls were not yet pubescent during the first round, and
      the whole sample displayed growth retardation in weight and stature, compared
      with the World Health Organization/National Center for Health Statistics
      reference. RESULTS: Estimated levels of activity were high, ranging from 1.80 to
      1.85 multiples of basal metabolic rate. There was a clear decline in the activity
      level during the course of study. Schoolgirls were less active than the others.
      Mature adolescents showed more activity during the night. A weak, but significant
      and positive correlation existed between body mass index and activity during the
      day; during the night, there was a positive correlation with fat and lean body
      mass. CONCLUSION: Factors determining the activity level were intricate but
      greater maturity and better nutritional status appeared to be positively related
      to the activity level.

PMID- 11287252
TI  - Dietary intake as a cardiovascular risk factor in Costa Rican adolescents.
AB  - PURPOSE: To evaluate Costa Rican adolescents' dietary intake as a cardiovascular
      disease (CVD) risk factor. METHODS: Dietary intake was determined using 3-day
      food records; nutrient content of fast foods prepared in school cafeteria was
      calculated by the weighted records. RESULTS: Around 30% of adolescents exceed the
      American Heart Association dietary recommendation for total fat and saturated
      fat. About 50% reported a cholesterol intake higher than 100 mg/1000 kcal. On
      average, 45% of adolescents do not meet the dietary fiber recommendation of 10
      g/1000 kcal, the 66% of the recommended daily allowance for vitamins E and B(6),
      or around 25% for folic acid. A higher proportion of urban adolescents do not
      satisfy the established dietary recommendation to prevent CVD. CONCLUSIONS: To
      avoid further increases in the Costa Rican CVD mortality rate, it is necessary to
      develop primary prevention programs, oriented to modify adolescent's nutrition
      habits. Schools have the potential to carry out such programs, as at least 60% of
      all adolescents in Costa Rica are enrolled in high schools.

PMID- 11287253
TI  - Eating disorders and altered eating behaviors in adolescents of normal weight in
      a Spanish city.
AB  - PURPOSE: To study the prevalence of altered eating behaviors or eating disorder
      related behaviors among adolescents of normal weight that do not fulfill criteria
      for anorexia nervosa and bulimia nervosa. METHOD: Cross-sectional study by means
      of a self-completed questionnaire (School of Nutrition of Granada, Spain) and
      measurement of weight and height in a population of 491 schoolchildren aged 14-18
      years. The statistical inferences and estimation of risk are based on comparison
      of proportions and means test, and the relative inequality of prevalences.
      RESULTS: Of 491 adolescents of normal weight, 9% (females 2:1) were following
      diets; 42% presented "recurrent episodes of binging" with the sensation of loss
      of self-control; and 41%% avoided specific types of food. Overall, 46.2%
      presented altered eating behavior. Factors significantly associated with this
      were the occurrence of periods of food abstinence and the use of purgatives
      [confidence interval 95% (CI 95%) prevalence ratio (PR) 1.41-2.02]. Compensatory
      behaviors were present in 33% of the adolescents, predominantly in females (CI
      95% PR 1.79-3.07). The prevalences of abnormal eating behaviors were 16.3% for
      those related to anorexia (A-RB) and 17.1% for those related to bulimia (B-RB),
      with a clear predominance of females (2:1) and public education. There seems to
      be a greater aesthetic concern among those with B-RB and more worry about weight
      among those with A-RB. CONCLUSIONS: A high proportion of adolescents with
      abnormal eating behaviors and an altered perception of body fat may currently be
      diagnosed as having atypical eating disorder" (Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Revision) considering that their body mass index was
      within normal range.

PMID- 11287254
TI  - Early puberty and early sexual activity are associated with bulimic-type eating
      pathology in middle adolescence.
AB  - PURPOSE: To examine the associations between early pubertal timing and early
      advanced sexual development with bulimic-type eating pathology in middle
      adolescents. METHODS: A total of 19,321 boys and 19,196 girls aged 14-16 years
      (mean age 15.3 years, standard deviation 0.59) responded to the School Health
      Promotion Study, a class-room survey among Finnish adolescents about health,
      health behavior, and school experiences. Bulimic-type eating pathology was
      assessed with a questionnaire formulated according to the fourth edition of the
      Diagnostic and Statistical Manual for Mental Disorders IV (DSM-IV) criteria.
      Pubertal timing was assessed by self-reported age at menarche or oigarche.
      Statistical methods were used chi-square and logistic regression. RESULTS:
      Bulimic-type eating pathology among girls was associated with early menarche,
      early sexual experiences, and increasing age. Among boys, onset of ejaculations
      at the normative age was protective for bulimic-type eating pathology, and the
      risk was elevated among very early and late maturers. Early sexual experience was
      associated with bulimic-type eating pathology. CONCLUSION: To prevent bulimia
      nervosa and to create opportunities for early intervention, attention should be
      paid to early maturing girls and off-time maturing boys, as well as those with
      early onset of sexual activity.

PMID- 11287255
TI  - Bilateral breast cancer--under age 20 years.

PMID- 11287257
TI  - Expanding cerebellar horizons.
AB  - Anatomical connections must underly neuronal function. A new study by Middleton
      and Strick shows that the cerebellum projects to the dorsal prefrontal cortex of
      the monkey. This could provide the basis for cerebellar modulation of cognitive
      processes.

PMID- 11287258
TI  - Morphological tensions.

PMID- 11287259
TI  - Probing Mus silicium.

PMID- 11287260
TI  - When bottom-up meets top-down.

PMID- 11287261
TI  - Two new face illusions.

PMID- 11287262
TI  - Sociable computing.

PMID- 11287264
TI  - ANTS in space?

PMID- 11287263
TI  - Plum take-away.

PMID- 11287265
TI  - Topping the science charts.

PMID- 11287266
TI  - Perfect pitch.

PMID- 11287267
TI  - How evolutionary history shapes recognition mechanisms.
AB  - Evolutionary psychologists have emphasized the importance of natural selection in
      shaping cognitive functions, but historical contingency has not received direct
      study. This is crucial because in response to selection, complex traits tend to
      be fine-tuned or jury-rigged rather than totally reconstructed. We hypothesize
      that the neural and cognitive strategies an animal employs in signal recognition
      are influenced by the strategies used by its ancestors. The responses of female
      tungara frogs to ancestral calls and to calls of other closely related species
      are influenced by history. By training artificial neural networks with a series
      of calls that mimic the species' past history of call evolution or various
      control histories, we have shown that only networks that evolved through the
      mimetic history predict the response biases of tungara frogs.

PMID- 11287268
TI  - Capgras delusion: a window on face recognition.
AB  - Capgras delusion is the belief that significant others have been replaced by
      impostors, robots or aliens. Although it usually occurs within a psychiatric
      illness, it can also be the result of brain injury or other obviously organic
      disorder. In contrast to patients with prosopagnosia, who cannot consciously
      recognize previously familiar faces but display autonomic or covert recognition
      (measured by skin conductance responses), people with Capgras delusion do not
      show differential autonomic activity to familiar compared with unknown faces.
      This challenges traditional models of the way faces are identified and presents
      some epistemological questions concerning identity. New data also indicate that,
      contrary to previous evidence, covert recognition can be fractionated into
      autonomic and behavioural/cognitive types, which is consistent with a recently
      proposed modification of the modal face recognition model.

PMID- 11287269
TI  - Eye movements during reading: some current controversies.
AB  - For many researchers, eye-movement measures have become instrumental in revealing
      the moment-to-moment activity of the mind during reading. In general, there has
      been a great deal of consistency across studies within the eye-movement
      literature, and researchers have discovered and examined many variables involved
      in the reading process that affect the nature of readers' eye movements. Despite
      remarkable progress, however, there are still a number of issues to be resolved.
      In this article, we discuss three controversial issues: (1) the extent to which
      eye-movement behavior is affected by low-level oculomotor factors versus higher
      level cognitive processes; (2) how much information is extracted from the right
      of fixation; and (3) whether readers process information from more than one word
      at a time.

PMID- 11287270
TI  - Human intelligence differences: towards a combined experimental-differential
      approach.
AB  - Despite the fact that much is known about the taxonomy and predictive validity of
      human intelligence differences, there has been relatively little progress in
      understanding their cognitive bases. However, some recent firm findings mark the
      beginnings of a cognitive reductionism in human intelligence. Progress towards
      discovering 'cognitive components' that, firstly, show individual differences
      and, secondly, relate to psychometric intelligence differences is described here
      at different nominal levels of analysis: 'psychometric', 'cognitive-experimental'
      and 'psychophysical'. The field of intelligence differences remains a fertile yet
      seriously under-developed demesne in which cognitive scientists should
      collaborate with differential psychologists.

PMID- 11287271
TI  - Discerning intentions in dynamic human action.
AB  - When we observe others in motion, we usually care little about the surface
      behaviors they exhibit. What matters are their underlying intentions. Judgments
      about intentions and intentionality dictate how we understand and remember
      others' actions, how we respond, and what we predict about their future action. A
      generative knowledge system underlies our skill at discerning intentions,
      enabling us to comprehend intentions even when action is novel and unfolds in
      complex ways over time. Recent work spanning many disciplines illuminates some of
      the processes involved in intention detection. We review these developments and
      articulate a set of questions cutting across current theoretical dividing lines.

PMID- 11287272
TI  - Cultural and dietary risk factors of oral cancer and precancer--a brief overview.
AB  - This is an update on cultural and dietary risk factors for oral precancer and
      cancer. It is an overview on ethnic differences (where possible) and socio
      cultural risk factors (tobacco/areca nut/betel quid, alcohol use and dietary
      factors) in relation to oral precancer and cancer. While studies were from
      Western countries, India and China, this update also attempts to include and
      highlight some studies conducted in the Asia-Pacific region.

PMID- 11287274
TI  - Factors related to advanced stage oral squamous cell carcinoma in southern
      Thailand.
AB  - A critical factor that indicates a poor prognosis of oral squamous cell carcinoma
      (OSCC) is advanced stage disease. This study, therefore, aimed to identify the
      factors related to advanced stage (TNM staging III, IV) OSCC in Thailand. There
      were 161 patients with squamous cell carcinoma of the oral cavity and lip (ICD-9
      140, 141, 143-5), included in the study. Sixty-two per cent of the patients
      presented with advanced stage disease. Information on demographic
      characteristics, risk habits, health-seeking behaviour prior to health care
      professional (HCP) consultation, tumour characteristics and patient and
      professional delay was obtained by questionnaire-based interview of the patients.
      These variables were included as initial variables in a logistic regression to
      calculate the odds ratio (OR) of advanced versus early stage OSCC. Having
      traditional herbal medication before HCP consultation significantly increased the
      risk of advanced stage OSCC (OR 5.77; 95% C.I. 1.25-26.62). Floor of mouth
      location of tumour was associated with a lower risk of advanced stage disease (OR
      0.27; 95% C.I. 0.09-0.82) as was having an ulcer (OR 0.43, 95% C.I. 0.02-0.89).
      The findings indicate that having traditional herbal medication before HCP
      consultation increased the risk of advanced stage disease. The lower risk of
      advanced stage OSCC associated with ulcerative tumours and those on the floor of
      the mouth may be due to their being more readily detected by the patients.

PMID- 11287273
TI  - Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno
      associated virus vector.
AB  - The purpose of this study was to test the possibility of gene transfer as a new
      therapy for oral cancer. Adeno-associated virus (AAV) has already been used in
      the fields of cystic fibrosis and Parkinson's disease as a potential vector for
      gene therapy because of its wide host range, high transduction efficiency, and
      lack of cytopathogenicity. Four human oral squamous cell carcinoma cell lines
      were transduced with an AAV vector containing the beta-galactosidase gene
      (AAVlacZ) in vitro. Gene transduction efficiency was from 20 to 50% at a
      multiplicity of infection (MOI; for the purposes of this study the number of
      vector genomes per target cell) of 1x10(3), and nearly 100% of each cell line
      were transduced at an MOI of 1x10(4). Next, four cell lines were transduced with
      an AAV vector containing the herpes simplex virus thymidine kinase (HSVtk) gene,
      which sensitizes transduced cells to ganciclovir (GCV). Subsequent administration
      of GCV resulted in nearly 100% tumor cell killing at an MOI of 1x10(4) and from
      70 to 80% tumor cell killing at an MOI of 1x10(3). These results suggest that AAV
      mediated gene transfer of HSVtk and administration of GCV has potential as a new
      therapy for oral squamous cell carcinoma.

PMID- 11287275
TI  - Mutational analysis of the candidate tumor suppressor gene ING1 in Indian oral
      squamous cell carcinoma.
AB  - ING1, a recently identified candidate tumor suppressor gene, involved in the p53
      signaling pathway is mapped at chromosome 13q34. Since loss of heterozygosity at
      13q34 has been reported in squamous cell carcinoma of head and neck, we screened
      for mutations in ING1 by polymerase chain reaction-single strand conformation
      polymorphism in 71 oral squamous cell carcinomas (OSCC) from India, 15 of which
      were known to harbor p53 mutations. A single polymorphism (G to A) was detected
      in 14 (19.7%) of the tumors analyzed. No mutation was observed in any of the 71
      OSCCs analyzed. These results suggest that ING1 is not a target for mutational
      inactivation in OSCC of Indians.

PMID- 11287276
TI  - Overexpression of BMP-2/4, -5 and BMPR-IA associated with malignancy of oral
      epithelium.
AB  - The aim of the present study was to determine the relationships between bone
      morphogenetic proteins (BMPs), BMP receptor type IA and carcinogenesis of oral
      epithelium. A retrospective study was performed on material obtained from oral
      mucosa, including nine cases of normal mucosa (NB), eight cases of nonspecific
      chronic inflammation (NCI), seven cases of hyperkeratosis (HK), five cases of
      squamous cell papilloma (SCP), 29 cases of squamous cell carcinoma (SCC) with
      various grades of differentiation and 10 cases of epithelium adjacent to
      carcinoma (EAC). Six cases of NB from hard palate (NHP) were chosen as a control
      group. The benign groups consisted of NCI, HK and SCP. The antibodies against BMP
      2/4, -5, receptor BMPR-IA and purified bovine BMP (bBMP-McAb) were utilised using
      an immunocytochemical method. The results demonstrated that the immunostaining of
      BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb was weak and not consistent in normal and
      benign groups. The immunoreactivity level was independent of the clinical and
      pathological grading of SCC. All cases of SCC showed positive staining for BMP
      2/4, BMP-5, BMPR-IA and bBMP-McAb except for three cases and one case of SCC
      which negatively stained for BMP-2/4 and BMP-5, respectively. The staining
      intensity and proportion of the positively stained cells were markedly increased
      in SCC when compared with that of the normal and benign groups except for EAC.
      The metastatic carcinoma cells in lymph nodes were strongly and positively
      stained for BMP-2/4 and BMP-5 when compared with the primary lesions. Our results
      indicate that there was an overexpression of BMP-2/4, BMP-5, bBMP-McAb and BMPR
      IA in the high-risk premalignant and malignant lesions of oral epithelium. Our
      findings suggest that BMP-2/4 and BMP-5 but not BMPR-IA might be involved in the
      metastasis of oral carcinoma cells.

PMID- 11287277
TI  - Fibrin induces IL-8 expression from human oral squamous cell carcinoma cells.
AB  - In recent studies, we have demonstrated that fibrin is present in association
      with tumor cells in oral squamous cell carcinoma (OSCC) in vivo. We hypothesized
      that this fibrin can directly induce the expression of known angiogenic factors
      from oral tumor cells. Since IL-8 is known to be the major inducer of
      angiogenesis caused by these cells, we examined the ability of fibrin to
      stimulate IL-8 expression from OSCC cells in vitro. A physiologically relevant
      concentration of fibrin was found to cause a dose and time-dependent stimulation
      of IL-8 expression from oral and pharyngeal tumor cells but not from a non
      tumorigenic oral cell line. Fibrinogen, thrombin and collagen were all unable to
      induce significant IL-8 expression, establishing the specificity of fibrin in
      causing this response. Gel filtration chromatography confirmed the molecular
      identity of the IL-8 antigen detected in the ELISA system used. These results
      suggest that fibrin may promote angiogenesis in oral tumors in vivo by directly
      upregulating the expression of IL-8 from tumor cells.

PMID- 11287278
TI  - Correlation between p53 gene mutations and circulating antibodies in betel- and
      tobacco-consuming North Indian population.
AB  - Alterations in p53 tumour suppressor gene and its expression may be implicated in
      the pathogenesis of betel- and tobacco-related oral cancer. There is wide
      regional variation in betel- and tobacco-consuming habits in different parts of
      the Indian subcontinent. The purpose of this study was to determine the
      correlations between p53 gene mutations, protein accumulation and serum
      antibodies in oral precancer and cancer. We analysed 30 potentially malignant
      oral lesions (leukoplakia) and 30 oral squamous cell carcinomas (SCCs) from
      northern India because the betel quid-consuming habits are different from those
      prevalent in other regions of India. p53 mutations were analysed by polymerase
      chain reaction amplification of genomic DNA and direct sequencing, p53 protein
      accumulation by immunohistochemical analysis and circulating p53 antibodies by
      ELISA. p53 gene mutations, analysed within exons 5-9, were observed in five out
      of 30 (17%) potentially malignant oral lesions and seven out of 30 (23%) oral
      SCCs. All the mutations were base substitution mutations. Three missense and two
      nonsense mutations were observed in potentially malignant oral lesions, while six
      missense and one nonsense mutations were identified in oral SCCs. The probable
      hot spots for the mutations were identified at codons 126, 136 and 174, which
      have not been observed thus far. A good correlation was observed between p53
      missense mutation, p53 antibodies and p53 protein accumulation in matched
      potentially malignant and malignant oral lesions. All the potentially malignant
      and cancerous lesions harbouring missense mutations showed accumulation of p53
      protein and the majority of these patients showed circulating p53 antibodies
      suggesting that serological detection of p53 antibodies may serve as a surrogate
      marker for p53 alterations in oral lesions.

PMID- 11287279
TI  - Gene expression of differentiation-specific keratins in oral epithelial dysplasia
      and squamous cell carcinoma.
AB  - The aim of the study was to investigate the differentiation-specific keratins
      (K4, K13, K1 and K10) in oral epithelial dysplasia and squamous cell carcinoma
      (SCC). Alterations in keratin gene expression were determined by in situ
      hybridization using 35S-labeled riboprobes and immunohistochemistry with
      monoclonal antibodies. In mild dysplasia, both sets of differentiation keratins
      were expressed in the same group of cells but in moderate lesions, expression of
      K4 and K13 was reduced in the presence of enhanced K1 and K10 synthesis. In
      severe dysplasia, neither mRNAs nor proteins were detected. In tumor islands of
      well and moderately differentiated SCCs, the K4/K13 complex was co-expressed with
      K1/K10, but in poorly differentiated carcinomas, differentiation keratins were
      absent. Consequently, mild oral epithelial dysplasia and well differentiated SCC
      retain an essentially normal pattern of keratin gene expression and hence
      epithelial differentiation while in severe dysplasia and poorly differentiated
      SCC keratin gene expression reflects the gross changes in epithelial
      differentiation and maturation.

PMID- 11287280
TI  - Clinical guidelines in early detection of oral squamous cell carcinoma arising in
      oral lichen planus: a 5-year experience.
AB  - In recent years, studies on the malignant potential of oral lichen planus (OLP)
      provided clinical evidence that patients affected by OLP have an increased risk
      to develop oral squamous cell carcinoma (OSCC); nevertheless, controversies still
      exist as to whether OLP has inherent predisposition to become malignant, or not.
      We believe extremely careful management of OLP patient is mandatory, and the aim
      of this paper is to illustrate our clinical guidelines in evaluating the possible
      risk of transformation in OLP lesions. Five-hundred and two patients (311 women
      and 191 men) affected by OLP regularly undergo follow-up examination in our
      Department. Patients' ages range from 18 to 83 years, with a mean of 55.4 years
      (57.5 for women and 53.9 for men); minimal follow-up period is 4 months, with a
      maximum of 12 years. In our group of OLP patients in the past 5 years we detected
      24 carcinomas: excluding three cases in which diagnoses of OLP and OSCC were
      synchronous and three patients who had a history of tobacco use, thus possible
      malignant transformation of OLP would appear to be 3.7%. Clinical criteria used
      in our follow-up allowed us to detect 28.5% of tumours as in situ OSCC, 38% as
      microinvasive OSCC, 28.5% as stage I OSCC and 4.7% as stage II OSCC, with a
      remarkable improvement in prognosis compared to our previous study in which we
      adopted different criteria.

PMID- 11287281
TI  - Frequent cyclin D1 gene amplification and protein overexpression in oral
      epithelial dysplasias.
AB  - Amplification of the cyclin D1 gene has been identified in 17-55% of head and
      neck squamous cell carcinoma. In some tumors, this alteration has been associated
      with decreased survival and increased recurrence rates. In precancerous lesions
      of the mouth, the frequency of cyclin D1 gene amplification is not known. In
      addition, it is unknown whether amplification of the gene translates to
      overexpressed cyclin D1 protein in these lesions. We examined 59 formalin-fixed,
      paraffin embedded tissue biopsies of oral epithelial dysplasias (OED) and 25 oral
      squamous cell carcinoma (SCC) from the floor of the mouth for cyclin D1 gene and
      protein levels. Genomic DNA was extracted from laser microdissected lesional
      tissue and a duplex, quantitative PCR assay was used to determine the
      amplification of the cyclin D1 gene relative to interferon-gamma. Cyclin D1
      protein expression was determined using immunohistochemistry and counting
      positive nuclei by computer image analysis. We found cyclin D1 gene amplification
      in 41% of mild, 45% of moderate and 24% of severe OEDs. Cyclin D1 was amplified
      in 36% of SCC. Overexpression of cyclin D1 protein was identified in 29% of mild,
      47% of moderate, 29% of severe OED's, and in 32% of SCC. Overexpression of cyclin
      D1 protein was identified in similar proportions of all grades of dysplasia and
      SCC. There were statistically significant correlations identified between gene
      and protein levels in all categories of disease. We concluded that amplification
      of the cyclin D1 gene is frequent in OED and that duplex, quantitative polymerase
      chain reaction is a reliable method to detect this change in routinely processed
      biopsies. The strong correlation between cyclin D1 gene amplification and protein
      levels suggests that this method may be suitable to assess cyclin D1 gene status
      in tissues not suitable for protein analysis.

PMID- 11287282
TI  - Lack of association between p53 expression and betel nut chewing in oral cancers
      from Thailand.
AB  - To elucidate whether betel-associated oral squamous cell carcinoma is associated
      with p53 protein expression, tumor samples from 156 patients with detailed
      histories of exposures were investigated immunohistochemically using CM1
      antibody. The expression of p53 (>10% positive cells) was found in 38.5% of the
      cases. The frequency of expression in betel chewers alone and betel chewer with
      tobacco use were 37.9% (11/29) and 25%(9/36), respectively, whereas that in betel
      chewers with smoking/drinking it was 47.2%(17/36) and in smokers or drinkers
      without chewing was 42.0% (21/50). However, the differences were not
      statistically significant. Multivariate analysis also revealed with the no
      independent association of betel chewing with p53 expression (odds ratio [OR]
      1.81, 95% confidence interval 0.50-6.49), whereas alcohol drinking and smokeless
      tobacco use were significant (OR 7.58, 2.01-28.53 and 0.39, 0.16-0.98,
      respectively). These results suggested that betel chewing with or without
      smokeless tobacco use may not induce oral cancers via a p53-dependent pathway.
      However, since this is an immunohistochemical study, further molecular analysis
      is needed.

PMID- 11287284
TI  - Amitotic cell divisions and tumour growth: an alternative model for cell kinetic
      compartments in solid tumours.
AB  - Previous studies on cytological assay of amitotic changes such as micronucleation
      or nuclear budding (akaryokinesis) and multinucleation (acytokinesis; Bhattathiri
      et al., Serial cytological assay of micronucleus induction--a new tool to predict
      human cancer radiosensitivity. Radiother Oncol 1996; 41: 139-142; Serial
      cytological assay of micronucleus induction--a new tool to predict human cancer
      radiosensitivity. Radiother Oncol. 1997; 41: 139-142; Radiation-induced acute
      immediate nuclear abnormalities in oral cancer cells. Serial cytologic
      evaluation. Acta Cytol 1998; 42: 1084-1090) had suggested that, in addition to
      predicting radiosensitivity, they may be related to proliferation characteristics
      of tumours. Hence the present study was undertaken to see if their pre-treatment
      frequency was related to the clinical growth characteristics of tumours. Smears
      from 121 untreated oral cancers were stained with Giemsa and the frequency, in
      percentage of total cells counted, of micronucleated or nuclear budded,
      binucleated and multinucleated cells taken as the akaryokinesis index (AKI),
      mitotic index (MI) and acytokinesis index (ACI), respectively were evaluated. The
      sum of AKI and MI was taken as the amitotic index (AMI), and the sum of AMI and
      MI as the cell division index (CDI). The tumours were divided to three groups
      according to size: <2 cm (Tsize1); 2-4 cm (Tsize2) and >4 cm (Tsize3). The
      tumours were divided to those with duration of <4 months and > or =4 months, this
      data having been collected from the patient. The differences in the frequency of
      the indices among the three size groups were analysed by Kruskall-Wallis one-way
      analysis of variance. Within each size group, the differences in frequency of the
      indices betwen the two duration groups was analysed by Mann-Whitney U test.
      Larger tumours had significantly higher CDI, the median frequency being 1.2, 2.29
      and 3.28% in Tsize1, Tsize2 and Tsize3 tumours, respectively (P=0.0025). In the
      case of AMi, the frequency was significantly higher the median values being 1.0,
      6.3 and 10.05%, respectively (P=0.0015). The difference was not significant in
      the case of the MI, the frequency being 0.69, 0.99 and 1.32%, respectively. AKI
      and ACI also showed significant increase. As regards relation to clinical growth,
      those tumours which reached larger size in shorter duration had higher frequency
      of MI. Those tumours which remained small in spite of a longer duration of growth
      had statistically significantly higher AKI whereas tumours which reached Tsize2
      in shorter duration of growth had significantly higher ACI. The results suggests
      that cytological evaluation of mitoses and amitoses can be helpful in evaluating
      proliferation characteristics of solid tumours. Micronucleated and multinucleated
      cells are clonogenically dead, but not physically so, but continue to divide for
      a few times before dying. The significant increase in AMI with size suggests that
      induction of amitoses is an important mechanism of cell loss as tumours enlarge,
      probably induced by associated hypovascularity, and precedes necrosis. The high
      frequency of amitoses in untreated tumours suggest that proliferation markers
      such as Tpot, growth fraction, etc., as measured by techniques such as
      flowcytometry, thymidine and BrdUrd labelling, etc., which do not evaluate
      amitoses, may essentially be wrong. Based on the findings of the study, an
      alternative model for tumour cell kinetic compartmentalisation, which includes a
      non-clonogenic compartment in addition to clonogenic and quiscent compartments,
      is presented.

PMID- 11287283
TI  - Co-expression of colligin and collagen in oral submucous fibrosis: plausible role
      in pathogenesis.
AB  - The high incidence of oral submucous fibrosis (OSF), a potentially malignant
      condition of the oral cavity, in the Indian subcontinent is causally associated
      with commonly prevailing habit of chewing areca nut and tobacco. Knowledge of
      molecular alterations in OSF is meagre. OSF is characterised by progressive
      accumulation of collagen fibres in lamina propria and oral submucosa.
      Colligin/HSP47 is a 47KDa stress protein which acts as a chaperone for collagen.
      We hypothesized that since colligin plays a vital role in folding and assembling
      collagen it may be involved in the pathogenesis of OSF. The present study was
      undertaken in tobacco and areca nut chewing Indian OSF patients to investigate
      the correlation, if any, between the expression of colligin and collagen type I
      proteins in OSF lesions. Immunohistochemical analysis showed overexpression of
      colligin and collagen type I proteins in 16/23 (70%) and 15/23 (65%) of OSF
      cases, respectively. The hallmark of the study was the significant association
      between the increased expression of type I collagen and its chaperone, colligin,
      in OSF lesions (P=0.0494). The data suggest that the increased levels of colligin
      in OSF may contribute to the deposition of collagen and consequent increased
      fibrosis in the oral submucosa in OSF lesions.

PMID- 11287285
TI  - Cisplatin inhibits the expression of X-chromosome-linked inhibitor of apoptosis
      protein in an oral carcinoma cell line.
AB  - Cisplatin is known to activate caspase-3 through the mitogen-activated kinase
      (MAPK) pathway. We found that X-chromosome-linked inhibitor of apoptosis protein
      (XIAP), a direct inhibitor of caspase-3, 7, and 9, is constitutively expressed in
      a cell line of oral squamous cell carcinoma, KOSC-2. Cisplatin treatment of the
      cells inhibited the expression of XIAP, and this was associated with DNA
      fragmentation. Overexpression of XIAP, by a transfection experiment, inhibited
      the cisplatin-induced apoptosis. We conclude that cisplatin induces apoptosis
      mediated not only by the activation of MAPK pathway but by the inhibition of
      XIAP.

PMID- 11287286
TI  - Establishment and characterization of an oral melanoma cell line (ME).
AB  - A new cell line, ME, has been established from a melanoma of the palatal mucosa.
      The cultured monolayer of cells was fusiform and melanin-producing. The cells
      were highly tumorigenic and metastatic in nude mice. The xenographic tumors
      resembled the original tumor in morphology, melanin production, and the
      expression of S-100 and HMB-45 antigens. The metaphase karyotype of ME indicated
      multiple aberrations of chromosomes 2, 3, 5, 7-11, 13, 19, 21 and X. A homozygous
      loss of the p16/MTS1 gene during the establishment of ME correlated with
      karyotypic evidence of chromosome 9 abnormalities. Absence of nm23 protein
      expression and elevated expression of CD44 protein (indicative of metastatic
      phenotypes) were demonstrated in primary and xenographic tumors. ME cells could
      be valuable in developing novel therapeutic strategies for oral melanoma.

PMID- 11287288
TI  - Expression of p53 tumor suppressor gene in adenoid cystic and mucoepidermoid
      carcinomas of the salivary glands.
AB  - Seventeen adenoid cystic carcinomas (ACCs) and 27 mucoepidermoid carcinomas
      (MECs) occurring in the salivary glands were analyzed for p53 tumor suppressor
      gene alteration (exons 5-8) and protein expression. The cell proliferation
      activity was also examined by Ki-67 immunohistochemistry. The p53 alterations
      were detected in three samples (17.6%) of ACC and in four samples (14.8%) of MEC,
      and were only found in carcinomas arising in the minor salivary glands. The
      occurrence of the p53 gene alteration is less frequent in ACC and MEC than that
      in other kinds of tumors, and therefore does not seem to play a critical role in
      the course of the tumorigenesis in ACC and MEC. All ACC samples arising from the
      minor salivary glands exhibiting p53 gene alterations showed
      recurrence/metastasis, thus suggesting a poor outcome of these patients. All ACCs
      and three out of four MECs samples with p53 gene alterations showed the lowest
      degree of p53 immunostaining ratio, thus suggesting that no correlation exists
      between the p53 gene alterations and the p53 immunostaining in these salivary
      gland carcinomas. No significant relationship was demonstrated between the
      immunostaining ratio of either p53 or Ki-67 and the morphological growth pattern
      or patient clinical course in the ACC samples. The p53 immunopositivity in MEC
      correlated to the histological grade. The Ki-67 immunostaining ratio was also
      significantly related to the histological grade and the clinical course in MEC.

PMID- 11287287
TI  - Expression of Rb, pRb2/p130, p53, and p16 proteins in malignant melanoma of oral
      mucosa.
AB  - We previously reported that pRb2/p130 gene, one of the Rb family members, was
      immunohistochemically abundantly expressed in well-differentiated oral squamous
      cell carcinomas, whereas in undifferentiated ones the expression was low. Oral
      malignant melanoma is extremely rare, however the prognosis is poor because it
      tends to locally invade tissue or metastasize and its biological behavior appears
      to be different from cutaneous malignant melanoma. The present study dealt with
      the expression of pRb2/p130, Rb, p53, and p16 in 13 cases of malignant melanoma
      of oral mucosa as revealed by immunohistochemical staining. The stage
      classification of the 13 patients was as follows; stage II: eight patients, stage
      III: three patients, and stage IV: two patients. pRb2/p130 was expressed in only
      two stage II-cases, neither of which have shown any evidence of recurrence or
      metastasis for over 14 years. Positive staining for Rb was found in three cases
      consisting of one stage II-case, one stage III-case, and one stage IV-case. p53
      was expressed in two cases, one a stage II and the other a stage IV. Positive
      staining for p16 was found in seven cases consisting of four stage II-cases, two
      stage III-cases, and one stage IV-case. pRb2/p130 may be inversely correlated
      with the malignancy of oral malignant melanoma, but further study is needed.

PMID- 11287289
TI  - Angiomyolipoma of the palate. Report of a case.
AB  - Angiomyolipoma (AML) is a tumour or an hamartomatous growth that usually affects
      the kidney. Only rarely has AML been described in the oral cavity. The authors
      report a case of AML located in the palate in a 43-year-old patient. AML is
      composed of smooth muscle cells, blood vessels and mature fat cells. In 50% of
      cases, AML presents with symptoms of tuberous sclerosis. Renal AML are often
      invasive, may involve regional nodes and may recur, while, on the contrary, AML
      are most often well circumscribed and easily resected. AML seems to follow an
      entire benign course.

PMID- 11287290
TI  - Verruciform xanthoma of the oral mucosa. Report of four cases and a review of the
      literature.
AB  - We present four new cases of verruciform xanthoma (VX) in the oral mucosa and
      review the literature. Clinical, histological, and immunohistochemical features
      of four new cases of VX were analysed together with cases found in a review of
      the literature. Expression of CD-68 was studied by immunohistochemistry. Only 162
      cases were reported in the oral mucosa. Ninety were males (55.5%) and 72 were
      females (44.5%). Mean age was 44.9 years. The majority of cases occurred in
      masticatory mucosa (69.7%). Our cases exhibited papillary or verrucous
      proliferation of squamous epithelium associated with hyperparakeratosis and with
      numerous foamy cells confined to the lamina propria papillae. Foamy cells were
      positive to CD-68 antibody, showing a macrophagic nature. VX is a rare benign
      lesion, and is probably inflammatory. However, its aetiology and pathological
      mechanisms remain unknown.

PMID- 11287291
TI  - Antioxidant vitamins C, E and beta-carotene reduce DNA damage before as well as
      after gamma-ray irradiation of human lymphocytes in vitro.
AB  - The protective effect of Vitamins C, E and beta-carotene against gamma-ray
      induced DNA damage in human lymphocytes in vitro was investigated. Cultured
      lymphocytes were exposed to increasing concentration of these vitamins either
      before or after irradiation with 2Gy of gamma-rays and DNA damage was estimated
      using micronucleus assay. A radioprotective effect was observed when antioxidant
      vitamins were added to cultured cells before as well after irradiation; the
      strongest effect was observed when they were added no later than 1h after
      irradiation. The radioprotective effect of vitamins also depended on their
      concentration; Vitamins C added at low concentration (1 microg/ml) before
      exposure of the cells to radiation prevented induction of micronuclei. Vitamin E
      at the concentration above 2 microg/ml decreased the level of radiation-induced
      micronuclei when compared to the cells irradiated without vitamin treatment. beta
      Carotene was effective at all tested concentrations from 1 to 5 microg/ml and
      reduced the number of micronuclei in irradiated cells. The vitamins had no effect
      on radiation-induced cytotoxicity as measured by nuclear division index. The
      radioprotective action of antioxidant Vitamins C, E and beta-carotene was
      dependent upon their concentration as well as time and sequence of application.

PMID- 11287292
TI  - Evaluation of micronuclei frequency in the cultured peripheral blood lymphocytes
      of cancer patients before and after radiation treatment.
AB  - The frequency of micronucleated binucleate lymphocyte (MNBNC) was determined in
      the peripheral blood lymphocytes of patients suffering from various types of
      cancer before the onset of radiation treatment, middle (mid-) of the treatment
      and after completion of the treatment (post-treatment). The frequency of
      micronuclei increased significantly in the pretreatment sample of cancer patients
      when compared with the normal untreated healthy volunteers. During the middle of
      the radiotherapy an approximate two or > two-fold increase was observed in the
      micronuclei frequency in most of the patients when compared with the concurrent
      pretreatment samples. Immediately after the completion of treatment, the
      frequency of micronuclei further increased, and this increase was significantly
      higher than that of pretreatment and mid-treatment samples. Out of 27 patients
      analyzed, only nine patients did not have any history of smoking, tobacco chewing
      or alcohol consumption, while the remaining 18 patients had a history of either
      smoking, tobacco chewing or alcohol consumption or combination of two or all
      habits at the time of blood collection.

PMID- 11287293
TI  - Induction and repair of DNA damage as measured by the Comet assay and the yield
      of somatic mutations in gamma-irradiated tobacco seedlings.
AB  - The advantage of using the tobacco (Nicotiana tabacum var. xanthi) mutagenicity
      assay is the ability to analyze and compare on the same plants under identical
      treatment conditions both the induced acute DNA damage in somatic cells as
      measured by the Comet assay and the yield of induced leaf somatic mutations.
      Gamma-irradiation of tobacco seedlings induced a dose-dependent increase in
      somatic mutations from 0.5 (control) to 240 per leaf (10Gy). The increased yield
      of somatic mutations was highly correlated (r = 0.996) with the increased DNA
      damage measured by the Comet assay immediately after irradiation. With increased
      dose of gamma-irradiation, the averaged median tail moment values ( +/- S.E.)
      significantly increased from 1.08 +/- 0.10 (control) to 20.26 +/- 1.61 microm
      (10Gy). Nuclei isolated from leaves 24h after irradiation expressed tail moment
      values that were not significantly different from the control (2.08 +/- 0.11).
      Thus a complete repair of DNA damage induced by gamma-irradiation and measurable
      by the Comet assay was observed, whereas the yield of somatic mutations increased
      in relation to the radiation dose. Data on the kinetics of DNA repair and of DNA
      damage induced by gamma-radiation on isolated tobacco nuclei, and on nuclei
      isolated from irradiated leaves and roots are presented.

PMID- 11287294
TI  - Cytogenetic analysis of children under long-term antibacterial therapy with
      nitroheterocyclic compound furagin.
AB  - Cytogenetic analysis of chromosome aberrations (CAs) and sister chromatid
      exchanges (SCEs) was performed in 109 blood samples from 95 pediatric patients
      with urinary tract infections (UTIs). Children were exposed to diagnostic levels
      of X-rays during voiding cystourethrography and subsequently treated for one to
      12 months with low doses of furagin - N-(5-nitro-2-furyl)-allylidene-1
      aminohydantoin. Furagin is 2-substituted 5-nitrofuran, chemically and
      structurally similar to well-known antibacterial compound nitrofurantoin.
      Increased frequencies of CAs were found in children undergoing voiding
      cystourethrography as compared with the unexposed, acentric fragments being the
      most frequent alteration (2.03 versus 0.88 per 100 cells, P=0.006). However, a
      significant decrease in the frequency of acentric fragments was determined with
      the time elapsed since X-ray examination was performed. A time-independent
      increase in SCE frequency was found in lymphocytes of children treated with
      furagin. Total CA frequency did not differ significantly between groups of
      children with various duration of furagin treatment. However, frequency of
      chromatid exchanges (triradials and quadriradials) increased significantly with
      duration of treatment.

PMID- 11287295
TI  - Prediction of the genotoxicity of aromatic and heteroaromatic amines using
      electrotopological state indices.
AB  - In the past decade, electrotopological state (E-state) indices have come into
      their own as useful descriptors for correlating a variety of physicochemical and
      biological properties of chemical compounds. Genotoxicity and mutagenicity,
      however, appear not to have been previously considered. In the present study, the
      genotoxicity of a set of 95 aromatic and heteroaromatic amines, which has been
      modeled previously using several sets of parameters, is modeled using E-state
      indices, both with and without principal components analysis. Parallels are drawn
      between E-state indices that were important in these models and other types of
      descriptors found significant in previous studies, thus, shedding light on
      connections to the molecular mechanism of activity. The best result had a
      correlation coefficient r = 0.876 and a standard error s< or = 1 log unit. These
      values are comparable to those in previously published models that were based on
      topological/geometric or on physicochemical parameters. They are not as good as
      those for a model based on descriptors derived from extensive quantum mechanical
      analysis, but E-state indices are much easier to compute.

PMID- 11287296
TI  - Micronuclei monitoring of fishes from Lake Paranoa, under influence of sewage
      treatment plant discharges.
AB  - Fish micronuclei tests (MN) were used to evaluate the ability of wastewater from
      two municipal sewage treatment plants that empty into Lake Paranoa to cause
      genetic damage. There were no significant differences in the frequencies of
      micronuclei between the control and hypertrophic areas. In contrast,
      cyclophosphamide and mitomycin C, used to test the sensitivity of the biological
      assay, significantly increased the micronuclei counts in Tilapia rendalli,
      Oreochromis niloticus and Cyprinus carpio, T. rendalli was the most sensitive
      specie to both clastogens and C. carpio, the most resistant.

PMID- 11287297
TI  - Role of reactive oxygen species in cupric 8-quinolinoxide-induced genotoxic
      effect.
AB  - This study demonstrates that cupric 8-quinolinoxide (CuQ) has induced genetic
      toxicity in bacteria and mammalian cells through a mechanism of reactive oxygen
      species (ROS) generation. In the Ames test with rat liver S9, CuQ dose
      dependently caused a point mutation in Salmonella typhimurium TA100. The effect
      of CuQ on DNA damage in HL60 and V79 cells identified in the comet assay is
      direct and enhanced by the addition of S9. Meanwhile, the tailing length of comet
      DNA is related to the increasing dosage of CuQ. The genotoxic effect of CuQ on
      either gene mutation in bacteria or DNA damage in culture cells can be generally
      blocked by several antioxidants, e.g. pyrrolidinedithiocarbamate, N
      acetylcysteine, Vitamins C and E. Supportive of this observation, ROS generation
      induced by CuQ can be demonstrated both in vitro and in vivo by using the DCFH-DA
      fluoroprobe. The CuQ-induced intracellular ROS level is also dramatically
      inhibited by the above antioxidants. Above results imply that the CuQ-induced
      genotoxicity could be mediated by ROS generation. The nature of ferrous-dependent
      and S9-enhancing in CuQ-induced ROS generation hints a Fenton-like reaction or
      some specific enzymes activation could be involved in this process. Furthermore,
      a DNA damage- and oxidative stress-dependent protein, P53, could also been
      induced by CuQ treatments in a time-course and dose-dependent manners. Its
      expression level is recoverable by antioxidants too. In conclusion, our current
      study strongly suggests that CuQ induces gene mutation, global DNA damage, and
      P53 expression through a ROS-dependent mechanism.

PMID- 11287298
TI  - Chromosome analysis of human spermatozoa following in vitro exposure to
      cyclophosphamide, benzo(a)pyrene and N-nitrosodimethylamine in the presence of
      rat liver S9.
AB  - For the purpose of assessing mutagenic effects (clastogenicity) of metabolites
      derived from chemical mutagens/carcinogens on human sperm chromosomes,
      spermatozoa were exposed in vitro to cyclophosphamide (CP), benzo(a)pyrene (BP)
      or N-nitrosodimethylamine (NDMA) for 2h in the presence or absence of rat liver
      S9, a metabolic activator of these chemicals. After in vitro fertilization
      between human spermatozoa and zona-free hamster oocytes, chromosome complements
      of sperm origin were analyzed cytogenetically. In the absence of S9, none of
      three chemicals (20 microg/ml CP, 200 microg/ml BP and 20mg/ml NDMA) caused a
      significant increase in spermatozoa with structural chromosome aberrations (8.6,
      10.0 and 7.5%), as compared with their matched controls (10.9, 11.0 and 8.5%). In
      the presence of S9, however, a significant increase in chromosomally abnormal
      spermatozoa was observed in CP (37.1%, P < 0.001) and BP (31.0%, P < 0.001),
      indicating that enzymatic activation of CP and BP induced chromosomal
      abnormalities in human sperm. In contrast, NDMA did not induce chromosome
      aberrations in human spermatozoa by S9 treatment, although positive results have
      been observed in somatic cells. The present results on in vitro clastogenicity of
      CP, BP and NDMA are consistent with the results in previous in vivo studies with
      murine spermatozoa. Our S9/human sperm chromosome assay seems to be useful for
      estimation of hereditary risk of chemicals in human. Because most chemicals need
      metabolic activation to bind to DNA.

PMID- 11287299
TI  - Identification of co-mutagenic chlorinated harmans in final effluent from a
      sewage treatment plant.
AB  - Harman (1-methyl-9H-pyrido[3,4-b]indole) reacted readily with sodium hypochlorite
      in an aqueous medium to give the mono-chlorinated derivatives, which reportedly
      have greater co-mutagenic activity than harman in the presence of o-toluidine
      toward Salmonella typhimurium TA 98 with S9 mix. Mono-chlorinated harmans were
      detected by concentration using blue rayon (BR) and GC/MS analysis in the final
      effluent from a sewage treatment plant in Shizuoka, Japan. The amounts adsorbed
      for 24h were 1-45ng/gBR for mono-chlorinated harman and 110-730ng/gBR for harman.

PMID- 11287300
TI  - Frequency of sister-chromatid exchange among greenhouse farmers exposed to
      pesticides.
AB  - Sister-chromatid exchange (SCE) was measured in peripheral lymphocytes of 104
      greenhouse farmers exposed to pesticides and 44 unexposed workers. The results of
      SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and,
      (b) proportion of high frequency cells (cells with more than eight SCEs). A high
      correlation was found between these two variables. The adjusted means of both
      SCEs variables were significantly higher among the farmers compared with the
      unexposed group (P < 0.01). Adjustment was made for smoking, age, education, and
      origin. The adjusted means of both SCE variables, were significantly elevated (P
      < 0.05) among the farmers who prepared and applied more than 70% of the
      pesticides by themselves compared with those who prepared and applied less than
      70% of the pesticides by themselves. Both SCEs variables were also significantly
      elevated (P < 0.05) among farmers who were involved in more than 7.4 sprays per
      year compared with those with 7.4 or less sprays per year (P < 0.05). We found a
      tendency towards elevation of the two variables of SCEs among those who did not
      use protective measures while preparing the pesticides. Evaluation of the
      influence of years of exposure on the frequency of SCEs showed that the two
      variables of SCEs were higher among those farmers who were exposed to pesticides
      for more than 21 years than among those with less than 21 years of exposure. The
      variables that had the most influence on the elevation of SCEs were self
      preparation of the pesticide mixtures and the number of sprayings per year.
      Because the farmers used a mixture of almost 24 different chemical classes it was
      impossible to attribute exposure to a specific pesticide or group of pesticides
      to single farmers. Our finding of a significant increase of SCEs frequency in
      peripheral lymphocytes in greenhouse farmers indicates a potential cytogenetic
      hazard due to pesticides exposure.

PMID- 11287301
TI  - Genotoxic effects of butadiene in mouse lung cells detected by an ex vivo
      micronucleus test.
AB  - Lung fibroblasts from BD-exposed mice have been analysed for the occurrence of
      micronuclei. Primary cultures set up 24h after the end of exposure were treated
      with cytochalasin B and micronuclei scored in binucleate cells. A three-fold
      statistically significant increase of micronucleated cells was detected after
      exposure to 500ppm, the lowest tested concentration. A linear dose effect
      relationship was observed between 500 and 1300ppm. Immunofluorescent staining of
      kinetochore proteins was applied to distinguish between acentric micronuclei
      produced by chromosome breaks and micronuclei containing a centromeric region,
      most likely induced by chromosome loss. A statistically significant increase of
      both types of MN in 1300ppm-exposed females and a significant increase in
      centromeric MN in 500ppm-exposed males were detected. These data demonstrate that
      an intermediate of BD metabolism with a potential for clastogenic and aneugenic
      effects is active in lung cells after inhalation exposure. These effects can play
      a role in the initiation and promotion of BD-induced lung tumours.

PMID- 11287302
TI  - Induction of micronuclei by 7H-dibenzo[c,g]carbazole and its tissue specific
      derivatives in Chinese hamster V79MZh1A1 cells.
AB  - The clastogenicity/aneugenicity of N-heterocyclic polycyclic aromatic pollutant
      7H-dibenzo[c,g]carbazole (DBC) and its two synthetic derivatives N-methyl DBC
      (MeDBC) and 5,9-dimethyl DBC (diMeDBC) was evaluated in the genetically
      engineered Chinese hamster V79 cell line V79MZh1A1 with stable expression of
      human cytochrome P4501A1 and in the parental V79MZ cell line without any
      cytochrome P450 activity. While none of the three carbazoles changed
      significantly the level of micronuclei in the parental V79MZ cells, a variable,
      but statistically significant rise of micronucleus frequencies was assessed in
      V79MZh1A1 cells. DBC induced dose-dependent increase in the number of micronuclei
      at harvest times of 24 and 48h and MeDBC at sampling time of 48h in V79MZh1A1
      cells in comparison to untreated cells, however, no significant time-dependent
      increase in micronucleus frequencies was found. The use of the antikinetochore
      immunostaining revealed that DBC and MeDBC induced approximately equal levels of
      both kinetochore positive (C+) and kinetochore negative (C-) micronuclei.
      DiMeDBC, a strict hepatocarcinogen, did not manifest any effect on micronucleus
      induction in V79MZh1A1 cells. These studies suggest that genetically engineered
      Chinese hamster V79 cell lines expressing individual CYP cDNAs are a useful in
      vitro model for evaluation the role of particular cytochromes P450 in
      biotransformation of DBC and its tissue and organ specific derivatives.

PMID- 11287303
TI  - Chromosome painting for cytogenetic monitoring of occupationally exposed and non
      exposed groups of human individuals.
AB  - The suitability of a three-color fluorescence in situ suppression hybridization
      technique was examined for monitoring five different groups of individuals: 30
      occupied in radiology, 26 occupied in nuclear medicine or radiation physics, 32
      patients with breast cancer, 26 occupied with military waste disposal, all
      presumably exposed to low doses of radiation or chemical mutagens and a non
      exposed control group (N=29). The average frequency of breaks constituting the
      various aberrations did not significantly differ between the groups of medical
      radiation appliers and the control group. However, breast tumor patients and
      military waste disposers, as groups, showed a higher aberration rate than did
      healthy controls. Stable rearrangements mainly characterized the groups of
      controls, tumor patients, and radiation appliers, while a higher proportion of
      unstable aberrations was found in the chemically exposed individuals. Individuals
      with an increased frequency of aberrations could be detected within each examined
      group, which clearly determined the average values of the whole group. With
      respect to interchromosomal distribution of the breakpoints constituting the
      found aberrations and the involvement of the labeled chromosomes in
      rearrangements, the observed values were very close to the expected ones in the
      controls. A rather similar trend of deviations from expectation was observed in
      all other groups. Chromosome 4 was slightly over-affected, while chromosome 2 was
      slightly underrepresented in all analyzed groups (except tumor patients).
      Rearrangements of the labeled chromosomes with the unlabeled ones exceeded
      expectation. In conclusion, chromosome painting if included in further attempts
      of human population monitoring will broaden the basis of argumentation with
      respect to health risks introduced by mutagen exposure.

PMID- 11287304
TI  - Influence of smokeless tobacco exposure on detoxification status and chromosomal
      damage in male and female habitues.
AB  - In India, a large number of tobacco chewers and masheri users are chronically
      exposed to tobacco genotoxicants. Detoxification processes involving cellular
      glutathione (GSH) and glutathione S-transferases (GST) determine the outcome of
      exposure to environmental mutagens including those present in tobacco. Hence, in
      this study, GSH levels, GST activity, GSTM1 genotype and cytogenetic damage were
      determined using lymphocytes from 114 smokeless tobacco habitues and controls.
      The study groups comprised of male tobacco chewers, female masheri users, and age
      and sex-matched controls. Irrespective of the tobacco habit, GSH levels and GST
      activity were higher in females than in males. In both the groups of habitues,
      GSH levels were similar to those in controls, while a significant reduction in
      GST activity was observed in tobacco chewers only. The frequency of cytogenetic
      alterations was significantly elevated in both the groups of habitues with
      respect to controls. However, break-type aberrations were more frequent in
      tobacco chewers while gaps were commonly observed in masheri users. Differences
      in the nature of chromosomal alterations in the two groups of habitues appeared
      to be related to variation in total tobacco exposure and gender-related
      differences in the efficacy of the GSH/GST detoxification system.

PMID- 11287305
TI  - The Salmonella mutagenicity assay in a surface water quality monitoring program
      based on a 20-year survey.
AB  - Since 1979, the Environmental Agency of Sao Paulo State in Brazil, CETESB, has
      been using the Salmonella mutagenicity assay to assess the quality of natural
      waters. This paper is a compilation of data obtained during the last 20 years
      from more than a thousand samples. Potencies up to 30,000 revertants/l were
      observed in 137 positive samples. The Salmonella typhimurium strain TA98 was more
      sensitive than TA100; 79% of the mutagenicity was detected by this strain,
      regardless of the presence of S9-mix. A classification of the mutagenic response
      was proposed to facilitate in the dissemination of the information to the public.
      The classification was low, moderate, high and extreme for samples with mutagenic
      potency (revertants/l equivalent) of < 500, 500-2500, 2500-5000 and > 5000,
      respectively. As a result of this effort to standardize methodologies, compile
      and classify the mutagenic effect of water pollution, in 1998, the Salmonella
      mutagenicity assay was officially and systematically included in the Sao Paulo
      State Water Quality Monitoring Program. This assay has proven to be a useful tool
      in the identification of important pollution sources. Correction and prevention
      actions in Water Pollution Control Programs were generated as a result.

PMID- 11287306
TI  - Persistence of aneuploid immature/primitive hemopoietic sub-populations in mice 8
      months after benzene exposure in vivo.
AB  - Benzene (bz) is a common environmental contaminant associated with increased risk
      of myeloid leukemia. Chronic bz exposure in vivo increases the frequency of
      aneuploid circulating lymphocytes in humans. However, there is no information
      about persistence of bz-associated aneuploidy in immature/primitive cells, at
      risk of leukemic transformation, after bz exposure in vivo. We explored the
      relationship between the induction and persistence of aneuploidy in primitive
      hemopoietic cells from mice that received oral doses of bz in vivo. Short- and
      long-term persistence of aneuploidy were evaluated in immature/primitive sub
      populations (Lin(-)c-kit(+)Sca-1(+)), as well as lymphoid and myeloid cells, 6
      days and 2-8 months after exposure. Mice receiving bz in a corn oil carrier, or
      corn oil alone, both have increased aneuploidy frequencies (1-5%, compared to <1%
      in untreated controls) in all sub-populations, 6 days after exposure. However,
      unlike bz-induced aneuploidy, corn oil-induced aneusomies are transient, with
      frequencies returning to background levels in lymphoid and myeloid cells, 9 weeks
      after exposure. The frequency (5-9%) of aneuploid lymphocytes and myeloid cells
      is higher at 9 weeks than at 6 days, suggesting that bz disrupts chromosomal
      segregation in differentiated cells and/or progenitors. About 8 months after bz
      exposure, the Lin(-)c-kit(+)Sca-1(+) sub-population contains up to 14% aneuploid
      cells with numerical chromosomal aberrations affecting chromosomes 2 or 11. These
      data demonstrate that bz induces DNA copy number changes in immature/primitive
      cells, and that these changes persist for long periods. Although, initial
      exposures are not leukemogenic, subsequent exposures of cells to genotoxins or
      oxidative radicals that induce additional genetic hits may increase the risk of
      transformation. The contribution of bz-induced aneuploidy in immature/primitive
      cells to leukemogenesis remains to be determined.

PMID- 11287307
TI  - DNA damage evaluated by alkaline single cell gel electrophoresis (SCGE) in
      children of Chernobyl, 10 years after the disaster.
AB  - Using the alkaline single cell gel electrophoresis (Comet) assay, the extent of
      DNA damage was evaluated in leukocytes of 43 Belarussian children (16 healthy and
      27 affected by thyroid cancer). Thirty-nine healthy children from Pisa (Italy)
      were enrolled in the study as controls. In addition to basal levels of DNA
      damage, leukocytes were treated in vitro with bleomycin (BLM), a radiomimetic
      drug, to evaluate a possible adaptive response in different groups of children.
      Results with the Comet assay indicated an increased level of DNA damage (P=0.037)
      in leukocytes of Belarussian children compared to the Italian control group. In
      addition, within the Belarus group, lower basal levels of DNA damage (P<0.001)
      were found in children with cancer compared to healthy children. Tumor affected
      children were living in less radiocontaminated areas (P<0.04) than the healthy
      children and there was a significant relationship (P=0.03) between the amount of
      environmental radiocontamination and DNA damage in leukocytes. There were no
      differences in the sensitivity of leukocytes from different groups of children to
      BLM, indicating the absence of an adaptive response. The lack of an adaptive
      response may have been due to the use of noncycling cells and/or the bleomycin
      dose chosen. Tests for the presence of clastogenic factors (CF) in the blood
      serum of children showed that 39% of the tumor affected children and 19% of the
      healthy children in the exposed group were positive as compared to the Italian
      control group (0%) (Chi-square test, P<0.04). The higher levels of genomic damage
      in children evaluated 10 years after the Chernobyl disaster could be related to
      the increased incidence of individuals with CF.

PMID- 11287308
TI  - Mutagen sensitivity of nasopharyngeal cancer patients.
AB  - Primary nasopharyngeal carcinomas (NPCs) may be of various types, including
      squamous cell carcinomas, undifferentiated carcinomas, and lymphoepitheliomas.
      Tumor initiation has been linked to the Epstein-Barr virus and, in some
      geographical regions, to alimentary factors. Possible hereditary components for
      the appearance of NPCs have not yet been clearly identified. In this study,
      genetic sensitivity to the genotoxic effects of carcinogenic xenobiotics as an
      endogenous risk factor of tumor initiation was investigated. The single cell
      microgel electrophoresis assay was used to quantify chemically-induced DNA damage
      in lymphocytes of 30 NPC patients and 30 non-tumor donors. The xenobiotics
      investigated were N'-nitrosodiethylamine, sodium dichromate, and nickel sulphate,
      with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and dimethyl sulfoxide (DMSO) as
      positive and negative controls, respectively. The extent of DNA migration in the
      solvent control cultures was not significantly different between the two groups
      (1.2+/-0.5 mean Olive tail moment and standard deviation of 30 individuals for
      NPC patients; 1.1+/-0.4 for non-tumor donors). With constant exposure and
      electrophoretic conditions, genotoxic effects of varying degrees were induced by
      the different xenobiotics in tumor and non-tumor patients (nickel sulphate: 7.1+/
      2.5 for NPC patients and 5.9+/-1.6 for non-tumor donors; sodium dichromate:
      18.1+/-5.3 for NPC patients and 16.2+/-5.4 for non-tumor donors; MNNG: 47.8+/
      13.3 for NPC patients and 52.7+/-13.6 for non-tumor donors). Only N'
      nitrosodiethylamine proved to induce significantly more DNA migration in
      lymphocytes of tumor patients (9.8+/-3.1) as compared to non-tumor patients
      (8.2+/-2.3). Although for sodium dichromate the degree of DNA migration did not
      significantly differ, variability in migration patterns proved to be lower in the
      tumor group. Mutagen sensitivity of NPC patients was shown to be elevated for a
      selected xenobiotic, whereas a general elevation of DNA fragility was not
      present. Further studies on mutagen sensitivity as an endogenous risk factor
      influencing the susceptibility of patients at the time of first diagnosis of
      nasopharyngeal carcinomas are warranted.

PMID- 11287309
TI  - Genotoxic effects of styrene-7,8-oxide in human white blood cells: comet assay in
      relation to the induction of sister-chromatid exchanges and micronuclei.
AB  - Styrene is used in the production of plastics, resins and rubber. The highest
      human exposures to styrene take place by inhalation during the production of
      fiberglass reinforced plastics. Styrene is metabolized mainly in the liver to
      styrene-7,8-oxide (SO), its principal in vivo mutagenic metabolite. In this
      study, human peripheral white blood cells were exposed to several SO
      concentrations (10-200 microM) in order to evaluate its genotoxic properties by
      means of comet assay, sister-chromatid exchanges (SCE) and cytokinesis-blocked
      micronucleus (MN) test, in addition to determine its clastogenic or aneugenic
      properties by combining MN with fluorescence in situ hybridization (FISH)
      procedures. Our results show that SO induces DNA damage, SCE and MN in human
      leukocytes in vitro at concentrations above 50 microM, and that there is a strong
      relationship between DNA damage, as measured by the comet assay, and cytogenetic
      damage induced by SO at the doses employed. SO shows preferentially a clastogenic
      activity and produces a cytostatic effect at high doses, reflected by the
      significant decrease of the calculated proliferation indices. A good dose-effect
      relationship is obtained in the three tests performed at the concentration range
      assayed.

PMID- 11287310
TI  - Lymphocyte DNA damage in bus manufacturing workers.
AB  - To study the effect of occupational exposure, smoking, and drinking on lymphocyte
      DNA damage in bus manufacturing workers, 346 employees (106 women and 240 men)
      from six job categories (welders, mechanics, painters, and assembling, auxiliary
      and managerial workers) in a bus manufacturing factory in Guangzhou were
      included. Significant differences of tail moment among the six job categories
      were found (P=0.003) with adjustment for age and gender. Smoking increased tail
      moment significantly (3.14 (2.89-3.40) versus 2.79 microm (2.63-2.97), P=0.023).
      Analysis of covariance showed that occupational exposure (P=0.001) and smoking
      (P=0.019) had significant effect on tail moment after adjusting for all factors,
      whereas age and gender had no effect on DNA damage. Stratified analysis showed
      that painters (P=0.002), auxiliary workers (P=0.011), and mechanics (P=0.044) had
      larger tail moments than managerial workers after adjusting for age, gender,
      smoking, and drinking.

PMID- 11287311
TI  - Mutagenicity in Salmonella typhimurium TA98 and TA100 of nitroso and respective
      hydroxylamine compounds.
AB  - Five aromatic nitroso compounds were prepared and their mutagenicity in
      Salmonella typhimurium strains TA98 and TA100 compared with that of the
      corresponding hydroxylamines and the previously studied nitroarenes. A remarkable
      correspondence of the dose-response curves was observed between the nitroso and
      the respective hydroxylamine compounds. This effect could be observed in TA98 and
      TA100. It was only marginally dependent on the metabolical activation by rat
      liver S9-mix. Even the presence of a bulky alkyl substituent either near to the
      functional group, or far away from it, previously shown to considerably influence
      the mutagenic properties of nitroarenes, does not remarkably affect the
      properties of the nitroso and hydroxylamine species. The similarity between the
      latter two is likely to be due to a fast reduction of the nitrosoarenes to the
      hydroxylamine species under the test conditions. It seems that enzymes are not
      responsible for that reduction step, because sterical crowding near the
      functional group does not influence that behaviour. The test results of the
      aromatic hydroxylamines bearing a bulky substituent show that there are at least
      two ways to influence the mutagenicity of an aromatic nitro compound by such a
      group. A substituent near the functional group (ortho-position) disturbs the
      enzymatic reduction of the nitro group, because 3-tert-butyl-4
      hydroxylaminobiphenyl and its corresponding nitroso compound are highly
      mutagenic, whereas 3-tert-butyl-4-nitrobiphenyl was previously shown to be
      inactive even after addition of S9-mix. In contrast, 4'-tert-butyl-4
      hydroxylaminobiphenyl with the tert-butyl group "far away" from the hydroxylamino
      functionality clearly shows decreased mutagenic activity suggesting a different
      influence of a substituent in that position. In addition, the substance shows
      only little cell toxicity even at higher concentrations. Both effects could be
      due to a reduced effective dose of the hydroxylamine in the cells compared to the
      non-alkylated compound, caused by a faster degradation of the hydroxylamine or a
      hindered interaction between that substance and the cells.

PMID- 11287312
TI  - The effects of 4'-alkyl substituents on the mutagenic activity of 4-amino- and 4
      nitrostilbenes in Salmonella typhimurium.
AB  - Six derivatives of trans-4-aminostilbene bearing different alkyl groups in the 4'
      position and six of the corresponding nitro compounds were synthesized and tested
      for their mutagenic potency in Salmonella typhimurium strains TA98 and TA100.
      Regarding the test series in presence of S9-mix, maximum activity was observed
      for those trans-4-aminostilbenes and trans-4-nitrostilbenes bearing small alkyl
      substituents like methyl and ethyl. More bulky substituents reduced the mutagenic
      potential in the order iso-propyl<sec-butyl<tert-butyl for the aminostilbenes.
      The corresponding nitrostilbenes showed a similar trend under these conditions
      although the mutagenic activity of the tert-butyl-substituted compound was
      unexpectedly high in TA100. In the series without metabolic activation the
      nitrostilbenes showed a continuous decrease of mutagenic activity with the size
      of the substituents (methyl>ethyl>iso-propyl>sec-butyl>tert-butyl). These trends
      have been compared with quantitative structure activity relationship (QSAR) model
      predictions, leading to the conclusion that steric demand is an important factor
      for mutagenicity of substituted aminostilbenes and nitrostilbenes. The unexpected
      result for the tert-butyl nitrostilbene tested with metabolic activation may be
      attributed to a different metabolic pathway.

PMID- 11287313
TI  - Mutation spectrum of o-aminoazotoluene in the cII gene of lambda/lacZ transgenic
      mice (MutaMouse).
AB  - The o-aminoazotoluene (AAT) has been evaluated as a possible human carcinogen by
      the International Agency for Research on Cancer. In rodents, it is carcinogenic
      mainly in the liver, and also in lung following long term administration. We
      previously examined in lambda/lacZ transgenic mice for the induction of lacZ
      mutations in liver, lung, urinary bladder, colon, kidney, bone marrow, and
      testis. AAT induced gene mutations strongly in the liver and colon. In the
      present report, we reveal the molecular nature of mutations induced by AAT in the
      lambda cII gene (the cII gene, a phenotypically selectable marker in the lambda
      transgene, has 294bp, which makes it easier to sequence than the original target,
      the 3kb lacZ gene). The cII mutant frequency in liver and colon was five and nine
      times higher, respectively, in AAT-treated mice than in control mice. Sequence
      analysis revealed that AAT induced G:C to T:A transversions, whereas spontaneous
      mutations consisted primarily of G:C to A:T transitions at CpG sites.

PMID- 11287314
TI  - Increased functional cell surface expression of CFTR and DeltaF508-CFTR by the
      anthracycline doxorubicin.
AB  - Cystic fibrosis (CF) is a disease that is caused by mutations within the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene. The most common
      mutation, DeltaF508, accounts for 70% of all CF alleles and results in a protein
      that is defective in folding and trafficking to the cell surface. However,
      DeltaF508-CFTR is functional when properly localized. We report that a single,
      noncytotoxic dose of the anthracycline doxorubicin (Dox, 0.25 microM)
      significantly increased total cellular CFTR protein expression, cell surface CFTR
      protein expression, and CFTR-associated chloride secretion in cultured T84
      epithelial cells. Dox treatment also increased DeltaF508-CFTR cell surface
      expression and DeltaF508-CFTR-associated chloride secretion in stably transfected
      Madin-Darby canine kidney cells. These results suggest that anthracycline analogs
      may be useful for the clinical treatment of CF.

PMID- 11287315
TI  - Evaluation of ovarian POMC mRNA through quantitative RT-PCR analysis in Rana
      esculenta.
AB  - The evaluation of changes in the expression of specific genes requires accurate
      measurement of the corresponding mRNA concentration, especially when the gene is
      expressed at a very low level. We previously showed that the proopiomelanocortin
      (POMC) gene is expressed in the ovary of the frog Rana esculenta, and, to
      evaluate its mRNA content in frog ovary, we have now developed a sensitive
      quantitative RT-PCR method. This study provides evidence for the validation of
      this method and for the effects of captivity and hypophysectomy on POMC gene
      expression in the ovary of this anuran. Our data indicate that ovarian POMC gene
      is involved in short-term captivity stress response and seems not influenced by
      pituitary. These results are discussed taking into account the knowledge of the
      role played by opioids in stress response; moreover, a local control of POMC gene
      expression is also suggested.

PMID- 11287316
TI  - Mac-1-dependent tyrosine phosphorylation during neutrophil adhesion.
AB  - Activated neutrophils display an array of physiological responses, including
      initiation of the oxidative burst, phagocytosis, and cell migration, that are
      associated with cellular adhesion. Under conditions that lead to cellular
      adhesion, we observed rapid tyrosine phosphorylation of an intracellular protein
      with an approximate relative molecular mass of 92 kDa (p92). Phosphorylation of
      p92 was inducible when Mac-1 was activated by phorbol 12-myristate 13-acetate,
      the beta(2)-specific activating antibody CBR LFA-1/2, or interleukin-8 (77 amino
      acids). In addition, tyrosine phosphorylation of p92 was dependent on engagement
      of Mac-1 with ligand. Several observations suggest that this event may be an
      important step in the signaling pathway initiated by Mac-1 binding. p92
      phosphorylation was specifically blocked with antibodies to CD11b, the alpha
      subunit of Mac-1, and was rapidly reversible on disengagement of the integrin
      ligand interaction. Integrin-stimulated phosphorylation of p92 created binding
      sites that were recognized in vitro by the SH2 domains of c-CrkII and Src. Our
      observations suggest that neutrophil adhesion mediated through the binding of the
      beta(2)-integrin Mac-1 initiates a signaling cascade that involves the activation
      of protein tyrosine kinases and leads to the regulation of protein-protein
      interactions via SH2 domains, a key process shared with growth factor signaling
      pathways.

PMID- 11287317
TI  - TNF-alpha inhibits flow and insulin signaling leading to NO production in aortic
      endothelial cells.
AB  - Endothelial cells release nitric oxide (NO) acutely in response to increased
      "flow" or fluid shear stress (FSS), and the increase in NO production is
      correlated with enhanced phosphorylation and activation of endothelial nitric
      oxide synthase (eNOS). Both vascular endothelial growth factor and FSS activate
      endothelial protein kinase B (PKB) by way of incompletely understood pathway(s),
      and, in turn, PKB phosphorylates eNOS at Ser-1179, causing its activation. In
      this study, we found that either FSS or insulin stimulated insulin receptor
      substrate-1 (IRS-1) tyrosine and serine phosphorylation and increased IRS-1
      associated phosphatidylinositol 3-kinase activity, phosphorylation of PKB Ser
      473, phosphorylation of eNOS Ser-1179, and NO production. Brief pretreatment of
      bovine aortic endothelial cells with tumor necrosis factor-alpha (TNF-alpha)
      inhibited the above described FSS- or insulin-stimulated protein phosphorylation
      events and almost totally inhibited FSS- or insulin-stimulated NO production.
      These data indicate that FSS and insulin regulate eNOS phosphorylation and NO
      production by overlapping mechanisms. This study suggests one potential mechanism
      for the development of endothelial dysfunction in disease states with alterations
      in insulin regulation and increased TNF-alpha levels.

PMID- 11287318
TI  - n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras
      activation in colonocytes.
AB  - Ras proteins are critical regulators of cell function, including growth,
      differentiation, and apoptosis, with membrane localization of the protein being a
      prerequisite for malignant transformation. We have recently demonstrated that
      feeding fish oil, compared with corn oil, decreases colonic Ras membrane
      localization and reduces tumor formation in rats injected with a colon
      carcinogen. Because the biological activity of Ras is regulated by
      posttranslational lipid attachment and its interaction with stimulatory lipids,
      we investigated whether docosahexaenoic acid (DHA), found in fish oil, compared
      with linoleic acid (LA), found in corn oil, alters Ras posttranslational
      processing, activation, and effector protein function in young adult mouse colon
      cells overexpressing H-ras (YAMC-ras). We show here that the major n-3
      polyunsaturated fatty acid (PUFA) constituent of fish oil, DHA, compared with LA
      (an n-6 PUFA), reduces Ras localization to the plasma membrane without affecting
      posttranslational lipidation and lowers GTP binding and downstream p42/44(ERK)
      dependent signaling. In view of the central role of oncogenic Ras in the
      development of colon cancer, the finding that n-3 and n-6 PUFA differentially
      modulate Ras activation may partly explain why dietary fish oil protects against
      colon cancer development.

PMID- 11287319
TI  - Characterization of nucleoside transport systems in cultured rat epididymal
      epithelium.
AB  - The nucleoside transport systems in cultured epididymal epithelium were
      characterized and found to be similar between the proximal (caput and corpus) and
      distal (cauda) regions of the epididymis. Functional studies revealed that 70% of
      the total nucleoside uptake was Na(+) dependent, while 30% was Na(+) independent.
      The Na(+)-independent nucleoside transport was mediated by both the equilibrative
      nitrobenzylthioinosine (NBMPR)-sensitive system (40%) and the NBMPR-insensitive
      system (60%), which was supported by a biphasic dose response to NBMPR
      inhibition. The Na(+)-dependent [(3)H]uridine uptake was selectively inhibited
      80% by purine nucleosides, indicating that the purine nucleoside-selective N1
      system is predominant. Since Na(+)-dependent [(3)H]guanosine uptake was inhibited
      by thymidine by 20% and Na(+)-dependent [(3)H]thymidine uptake was broadly
      inhibited by purine and pyrimidine nucleosides, this suggested the presence of
      the broadly selective N3 system accounting for 20% of Na(+)-dependent nucleoside
      uptake. Results of RT-PCR confirmed the presence of mRNA for equilibrative
      nucleoside transporter (ENT) 1, ENT2, and concentrative nucleoside transporter
      (CNT) 2 and the absence of CNT1. It is suggested that the nucleoside transporters
      in epididymis may be important for sperm maturation by regulating the
      extracellular concentration of adenosine in epididymal plasma.

PMID- 11287320
TI  - Cloning of a novel EGFR-related peptide: a putative negative regulator of EGFR.
AB  - Although epidermal growth factor receptor (EGFR) plays a key role in regulating
      cell proliferation, differentiation, and transformation in many tissues, little
      is known about the factor(s) that may modulate its function. We have isolated a
      cDNA clone from the rat gastroduodenal mucosa whose full length revealed 1,958 bp
      that contained 227 bp of 5'-untranslated region (UTR) and an open-reading frame
      encoding 479 amino acids, followed by 290 bp of 3'-UTR. It showed ~85% nucleotide
      homology to the external domain of the rat EGFR. We refer to the product of the
      newly isolated cDNA as EGFR-related protein (ERRP). In Northern blot analysis
      with poly(A)(+) RNA from different rat tissues, ERRP cDNA hybridized to several
      mRNA transcripts with the strongest reaction noted with a transcript of
      approximately 2 kb. Maximal expression of the 2-kb mRNA transcript was observed
      in the small intestine, followed by colon, liver, gastric mucosa, and other
      tissues. Transfection of ERRP cDNA into a colon cancer cell line, HCT116,
      resulted in a marked reduction in proliferation in monolayer and colony formation
      in soft agar compared with the vector-transfected controls. In another colon
      cancer cell line, Caco-2, with a tetracycline-regulated promoter system,
      induction of ERRP expression in the absence of doxycycline was associated with a
      marked reduction in EGFR activation and proliferation. We conclude that the ERRP
      cDNA may represent a new member of the EGFR gene family and that ERRP plays a
      role in regulating cell proliferation by modulating the function of EGFR.

PMID- 11287321
TI  - Na(+)/Ca(2+) exchange and its role in intracellular Ca(2+) regulation in guinea
      pig detrusor smooth muscle.
AB  - The role of Na(+)/Ca(2+) exchange in regulating intracellular Ca(2+)
      concentration ([Ca(2+)](i)) in isolated smooth muscle cells from the guinea pig
      urinary bladder was investigated. Incremental reduction of extracellular Na(+)
      concentration resulted in a graded rise of [Ca(2+)](i); 50-100 microM
      strophanthidin also increased [Ca(2+)](i). A small outward current accompanied
      the rise of [Ca(2+)](i) in low-Na(+) solutions (17.1 +/- 1.8 pA in 29.4 mM
      Na(+)). The quantity of Ca(2+) influx through the exchanger was estimated from
      the charge carried by the outward current and was approximately 30 times that
      which is necessary to account for the rise of [Ca(2+)](i), after correction was
      made for intracellular Ca(2+) buffering. Ca(2+) influx through the exchanger was
      able to load intracellular Ca(2+) stores. It is concluded that the level of
      resting [Ca(2+)](i) is not determined by the exchanger, and under resting
      conditions (membrane potential -50 to -60 mV), there is little net flux through
      the exchanger. However, a small rise of intracellular Na(+) concentration would
      be sufficient to generate significant net Ca(2+) influx.

PMID- 11287322
TI  - Protein kinase C-mediated desensitization of the neurokinin 1 receptor.
AB  - An understanding of the mechanisms that regulate signaling by the substance P
      (SP) or neurokinin 1 receptor (NK1-R) is of interest because of their role in
      inflammation and pain. By using activators and inhibitors of protein kinase C
      (PKC) and NK1-R mutations of potential PKC phosphorylation sites, we determined
      the role of PKC in desensitization of responses to SP. Activation of PKC
      abolished SP-induced Ca(2+) mobilization in cells that express wild-type NK1-R.
      This did not occur in cells expressing a COOH-terminally truncated NK1-R (NK1
      Rdelta324), which may correspond to a naturally occurring variant, or a point
      mutant lacking eight potential PKC phosphorylation sites within the COOH tail
      (NK1-R Ser-338, Thr-339, Ser-352, Ser-387, Ser-388, Ser-390, Ser-392, Ser
      394/Ala, NK1-RKC4). Compared with wild-type NK1-R, the t(1/2) of SP-induced
      Ca(2+) mobilization was seven- and twofold greater in cells expressing NK1
      Rdelta324 and NK1-RKC4, respectively. In cells expressing wild-type NK1-R,
      inhibition of PKC caused a 35% increase in the t(1/2) of SP-induced Ca(2+)
      mobilization. Neither inhibition of PKC nor receptor mutation affected
      desensitization of Ca(2+) mobilization to repeated challenge with SP or SP
      induced endocytosis of the NK1-R. Thus PKC regulates SP-induced Ca(2+)
      mobilization by full-length NK1-R and does not regulate a naturally occurring
      truncated variant. PKC does not mediate desensitization to repeated stimulation
      or endocytosis of the NK1-R.

PMID- 11287323
TI  - Stimulation of cardiac L-type calcium channels by extracellular ATP.
AB  - The co-release of ATP with norepinephrine from sympathetic nerve terminals in the
      heart may augment adrenergic stimulation of cardiac Ca(2+) channel activity. To
      test for a possible direct effect of extracellular ATP on L-type Ca(2+) channels,
      single channels were reconstituted from porcine sarcolemma into planar lipid
      bilayers so that intracellular signaling pathways could be controlled.
      Extracellular ATP (2-100 microM) increased the open probability of the
      reconstituted channels, with a maximal increase of approximately 2.6-fold and an
      EC(50) of 3.9 microM. The increase in open probability was due to an increase in
      channel availability and a decrease in channel inactivation rate. Other
      nucleotides displayed a rank order of effectiveness of ATP > alpha,beta-methylene
      ATP > 2-methylthio-ATP > UTP > adenosine 5'-O-(3-thiotriphosphate) >> ADP;
      adenosine had no effect. Several antagonists of P2 receptors had no impact on the
      ATP-dependent increase in open probability, indicating that receptor activation
      was not required. These results suggest that extracellular ATP and other
      nucleotides can stimulate the activity of cardiac L-type Ca(2+) channels via a
      direct interaction with the channels.

PMID- 11287324
TI  - Increased contractility and altered Ca(2+) transients of mouse heart myocytes
      conditionally expressing PKCbeta.
AB  - Activation of protein kinase C (PKC) in heart muscle signals hypertrophy and may
      also directly affect contractile function. We tested this idea using a transgenic
      (TG) mouse model in which conditionally expressed PKCbeta was turned on at 10 wk
      of age and remained on for either 6 or 10 mo. Compared with controls, TG cardiac
      myocytes demonstrated an increase in the peak amplitude of the Ca(2+) transient,
      an increase in the extent and rate of shortening, and an increase in the rate of
      relengthening at both 6 and 10 mo of age. Phospholamban phosphorylation and
      Ca(2+)-uptake rates of sarcoplasmic reticulum vesicles were the same in TG and
      control heart preparations. At 10 mo, TG skinned fiber bundles demonstrated the
      same sensitivity to Ca(2+) as controls, but maximum tension was depressed and
      there was increased myofilament protein phosphorylation. Our results differ from
      studies in which PKCbeta was constitutively overexpressed in the heart and in
      studies that reported a depression of myocyte contraction with no change in the
      Ca(2+) transient.

PMID- 11287325
TI  - Coupling of L-type voltage-sensitive calcium channels to P2X(2) purinoceptors in
      PC-12 cells.
AB  - Extracellular ATP elevates cytosolic Ca(2+) by activating P2X and P2Y
      purinoceptors and voltage-sensitive Ca(2+) channels (VCCCs) in PC-12 cells,
      thereby facilitating catecholamine secretion. We investigated the mechanism by
      which ATP activates VSCCs. 2-Methylthioadenosine 5'-triphosphate (2-MeS-ATP) and
      UTP were used as preferential activators of P2X and P2Y, respectively. Nifedipine
      inhibited the ATP- and 2-MeS-ATP-evoked cytosolic Ca(2+) concentration increase
      and [(3)H]norepinephrine secretion, but not the UTP-evoked responses. Studies
      with Ca(2+) channel blockers indicated that L-type VSCCs were activated after the
      P2X activation. Mn(2+) entry profiles and studies with thapsigargin revealed that
      Ca(2+) entry, rather than Ca(2+) release, was sensitive to nifedipine. Although
      P2X(2) and P2X(4) receptor mRNAs were detected, studies with pyridoxal phosphate
      6-azophenyl-2',4'-disulfonic acid revealed that P2X(2) was mainly coupled to the
      L-type VSCCs. The inhibitory effect of nifedipine did not occur in the absence of
      extracellular Na(+), suggesting that Na(+) influx, which induces depolarization,
      was essential for the P2X(2)-mediated activation of VSCCs. We report that
      depolarization induced by Na(+) entry through the P2X(2) purinoceptors
      effectively activates L-type VSCCs in PC-12 cells.

PMID- 11287326
TI  - Single-channel basis for conductance increase induced by isoflurane in Shaker H4
      IR K(+) channels.
AB  - Volatile anesthetics modulate the function of various K(+) channels. We
      previously reported that isoflurane induces an increase in macroscopic currents
      and a slowing down of current deactivation of Shaker H4 IR K(+) channels. To
      understand the single-channel basis of these effects, we performed nonstationary
      noise analysis of macroscopic currents and analysis of single channels in patches
      from Xenopus oocytes expressing Shaker H4 IR. Isoflurane (1.2% and 2.5%) induced
      concentration-dependent, partially reversible increases in macroscopic currents
      and in the time course of tail currents. Noise analysis of currents (70 mV)
      revealed an increase in unitary current (approximately 17%) and maximum open
      probability (approximately 20%). Single-channel conductance was larger
      (approximately 20%), and opening events were more stable, in isoflurane. Tail
      current slow time constants increased by 41% and 136% in 1.2% and 2.5%
      isoflurane, respectively. Our results show that, in a manner consistent with
      stabilization of the open state, isoflurane increased the macroscopic conductance
      of Shaker H4 IR K(+) channels by increasing the single-channel conductance and
      the open probability.

PMID- 11287328
TI  - Regulation of mitochondrial glutamine/glutamate metabolism by glutamate
      transport: studies with (15)N.
AB  - We focused on the role of plasma membrane glutamate uptake in modulating the
      intracellular glutaminase (GA) and glutamate dehydrogenase (GDH) flux and in
      determining the fate of the intracellular glutamate in the proximal tubule-like
      LLC-PK(1)-F(+) cell line. We used high-affinity glutamate transport inhibitors D
      aspartate (D-Asp) and DL-threo-beta-hydroxyaspartate (THA) to block extracellular
      uptake and then used [(15)N]glutamate or [2-(15)N]glutamine to follow the
      metabolic fate and distribution of glutamine and glutamate. In monolayers
      incubated with [2-(15)N]glutamine (99 atom %excess), glutamine and glutamate
      equilibrated throughout the intra- and extracellular compartments. In the
      presence of 5 mM D-Asp and 0.5 mM THA, glutamine distribution remained unchanged,
      but the intracellular glutamate enrichment decreased by 33% (P < 0.05) as the
      extracellular enrichment increased by 39% (P < 0.005). With glutamate uptake
      blocked, intracellular glutamate concentration decreased by 37% (P < 0.0001), in
      contrast to intracellular glutamine concentration, which remained unchanged. Both
      glutamine disappearance from the media and the estimated intracellular GA flux
      increased with the fall in the intracellular glutamate concentration. The labeled
      glutamate and NH formed from [2-(15)N]glutamine and recovered in the media
      increased 12- and 3-fold, respectively, consistent with accelerated GA and GDH
      flux. However, labeled alanine formation was reduced by 37%, indicating
      inhibition of transamination. Although both D-Asp and THA alone accelerated the
      GA and GDH flux, only THA inhibited transamination. These results are consistent
      with glutamate transport both regulating and being regulated by glutamine and
      glutamate metabolism in epithelial cells.

PMID- 11287327
TI  - Intracellular Ca(2+) signaling in endothelial cells by the angiogenesis
      inhibitors endostatin and angiostatin.
AB  - Intracellular signaling mechanisms by the angiogenesis inhibitors endostatin and
      angiostatin remain poorly understood. We have found that endostatin (2 microg/ml)
      and angiostatin (5 microg/ml) elicited transient, approximately threefold
      increases in intracellular Ca(2+) concentration ([Ca(2+)](i)). Acute exposure to
      angiostatin or endostatin nearly abolished subsequent endothelial [Ca(2+)](i)
      responses to carbachol or to thapsigargin; conversely, thapsigargin attenuated
      the Ca(2+) signal elicited by endostatin. The phospholipase C inhibitor U-73122
      and the inositol trisphosphate (IP(3)) receptor inhibitor xestospongin C both
      inhibited endostatin-induced elevation in [Ca(2+)](i), and endostatin rapidly
      elevated endothelial cell IP(3) levels. Pertussis toxin and SB-220025 modestly
      inhibited the endostatin-induced Ca(2+) signal. Removal of extracellular Ca(2+)
      inhibited the endostatin-induced rise in [Ca(2+)](i), as did a subset of Ca(2+)
      entry inhibitors. Peak Ca(2+) responses to endostatin and angiostatin in
      endothelial cells exceeded those in epithelial cells and were minimal in NIH/3T3
      cells. Overnight pretreatment of endothelial cells with endostatin reduced the
      subsequent acute elevation in [Ca(2+)](i) in response to vascular endothelial
      growth factor or to fibroblast growth factor by approximately 70%. Intracellular
      Ca(2+) signaling may initiate or mediate some of the cellular actions of
      endostatin and angiostatin.

PMID- 11287329
TI  - Nongenomic effect of testosterone on chloride secretion in cultured rat efferent
      duct epithelia.
AB  - Short-circuit current (I(sc)) technique was used to investigate the role of
      testosterone in the regulation of chloride secretion in cultured rat efferent
      duct epithelia. Among the steroids tested, only testosterone, and to a lesser
      extent, 5alpha-dihydrotestosterone (5alpha-DHT), reduced the basal and forskolin
      induced I(sc) in cultured rat efferent duct epithelia when added to the apical
      bathing solution. Indomethacin, a 3alpha-hydroxysteroid dehydrogenase, did not
      affect the inhibitory effect of 5alpha-DHT. The effect of testosterone occurred
      within 10-20 s upon application and was dose dependent with apparent IC(50) value
      of 1 microM. The effect was abolished by removal of Cl(-) but not HCO from the
      normal Krebs-Henseleit solution, suggesting that testosterone mainly inhibited
      Cl(-) secretion. The efferent duct was found to be most sensitive to
      testosterone, while the caput and the cauda epididymidis were only mildly
      sensitive. Cyproterone acetate, a steroidal antiandrogen, or flutamide, a
      nonsteroidal antiandrogen, did not block the effect of testosterone on the
      forskolin-induced I(sc), nor did protein synthesis inhibitors, cycloheximide, or
      actinomycin D. However, pertussis toxin, a G(i) protein inhibitor, attenuated the
      inhibition of forskolin-induced I(sc) by testosterone. Testosterone caused a dose
      dependent inhibition of forskolin-induced rise in cAMP in efferent duct cells. It
      is suggested that the rapid effect of testosterone was mediated through a
      membrane receptor that is negatively coupled to adenylate cyclase via G(i)
      protein. The role of nongenomic action of testosterone in the regulation of
      electrolyte and fluid transport in the efferent duct is discussed.

PMID- 11287330
TI  - Transcriptional regulation of rat Na(+)/H(+) exchanger isoform-2 (NHE-2) gene by
      Sp1 transcription factor.
AB  - The rat Na(+)/H(+) exchanger isoform-2 (NHE-2) gene promoter lacks a TATA box and
      is very GC rich. A minimal promoter extending from bp -36 to +116 directs high
      level expression of NHE-2 in mouse inner medullary collecting duct (mIMCD-3)
      cells. Four Sp1 consensus elements were found in this region. The introduction of
      mutations within these Sp1 consensus elements and DNA footprinting revealed that
      only two of them were utilized and are critical for basal transcriptional
      activation in mIMCD-3 cells. The use of Sp1, Sp3, and Sp4 antisera in
      electrophoretic mobility shift assays demonstrated that Sp1, Sp3, and Sp4 bound
      to this minimal promoter. We further analyzed the transcriptional regulation of
      NHE-2 by members of the Sp1 multigene family. In Drosophila SL2 cells, which lack
      endogenous Sp1, the minimal promoter cannot drive transcription. Introduction of
      Sp1 activated transcription over 100-fold, suggesting that Sp1 is critical for
      transcriptional regulation. However, neither Sp3 nor Sp4 was able to activate
      transcription in these cells. Furthermore, in mIMCD-3 cells, Sp1-mediated
      transcriptional activation was repressed by expression of Sp3 and Sp4. These data
      suggest that Sp1 is critical for the basal promoter function of rat NHE-2 and
      that Sp3 and Sp4 may repress transcriptional activation by competing with Sp1 for
      binding to core cis-elements.

PMID- 11287331
TI  - Acidification and glucocorticoids independently regulate branched-chain alpha
      ketoacid dehydrogenase subunit genes.
AB  - Acidification or glucocorticoids increase the maximal activity and subunit mRNA
      levels of branched chain alpha-ketoacid dehydrogenase (BCKAD) in various cell
      types. We examined whether these stimuli increase transcription of BCKAD subunit
      genes by transfecting BCKAD subunit promoter-luciferase plasmids containing the
      mouse E2 or human E1alpha-subunit promoter into LLC-PK(1) cells, which do not
      express glucocorticoid receptors, or LLC-PK(1)-GR101 cells, which we have
      engineered to constitutively express the glucocorticoid receptor gene.
      Dexamethasone or acidification increased luciferase activity in LLC-PK(1)-GR101
      cells transfected with the E2 or E1alpha-minigenes; acidification augmented
      luciferase activity in LLC-PK(1) cells transfected with these minigenes but
      dexamethasone did not. A pH-responsive element in the E2 subunit promoter was
      mapped to a region >4.0 kb upstream of the transcription start site.
      Dexamethasone concurrently stimulated E2 subunit promoter activity and reduced
      the binding of nuclear factor-kappaB (NF-kappaB) to a site in the E2 promoter.
      Thus acidification and glucocorticoids independently enhance BCKAD subunit gene
      expression, and the glucocorticoid response in the E2 subunit involves
      interference with NF-kappaB, which may act as a transrepressor.

PMID- 11287332
TI  - Differential expression and alternative splicing of TRP channel genes in smooth
      muscles.
AB  - Nonselective cation channels (NSCC) are targets of excitatory agonists in smooth
      muscle, representing the nonselective cation current I(cat). Na(+) influx through
      NSCC causes depolarizations and activates voltage-dependent Ca(2+) channels,
      resulting in contraction. The molecular identity of I(cat) in smooth muscle has
      not been elucidated; however, products of the transient receptor potential (TRP)
      genes have characteristics similar to native I(cat). We have determined the
      levels of TRP transcriptional expression in several murine and canine
      gastrointestinal and vascular smooth muscles and have analyzed the alternative
      processing of these transcripts. Of the seven TRP gene family members,
      transcripts for TRP4, TRP6, and TRP7 were detected in all murine and canine
      smooth muscle cell preparations. TRP3 was detected only in canine renal artery
      smooth muscle cells. The full-length cDNAs for TRP4, TRP6, and TRP7, as well as
      one splice variant of TRP4 and two splice variants of TRP7, were cloned from
      murine colonic smooth muscle. Quantitative RT-PCR determined the relative amounts
      of TRP4, TRP6, and TRP7 transcripts, as well as that of the splice variants, in
      several murine smooth muscles. TRP4 is the most highly expressed, while TRP6 and
      TRP7 are expressed at a lower level in the same tissues. Splice variants for
      TRP7, deleted for exons encoding amino acids including transmembrane segment S1,
      predominated in murine smooth muscles, while the full-length form of the
      transcript was expressed in canine smooth muscles.

PMID- 11287333
TI  - Nifedipine-activated Ca(2+) permeability in newborn rat cortical collecting duct
      cells in primary culture.
AB  - To characterize Ca(2+) transport in newborn rat cortical collecting duct (CCD)
      cells, we used nifedipine, which in adult rat distal tubules inhibits the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) increase in response to hormonal
      activation. We found that the dihydropyridine (DHP) nifedipine (20 microM)
      produced an increase in [Ca(2+)](i) from 87.6 +/- 3.3 nM to 389.9 +/- 29.0 nM in
      65% of the cells. Similar effects of other DHP (BAY K 8644, isradipine) were also
      observed. Conversely, DHPs did not induce any increase in [Ca(2+)](i) in cells
      obtained from proximal convoluted tubule. In CCD cells, neither verapamil nor
      diltiazem induced any rise in [Ca(2+)](i). Experiments in the presence of EGTA
      showed that external Ca(2+) was required for the nifedipine effect, while
      lanthanum (20 microM), gadolinium (100 microM), and diltiazem (20 microM)
      inhibited the effect. Experiments done in the presence of valinomycin resulted in
      the same nifedipine effect, showing that K(+) channels were not involved in the
      nifedipine-induced [Ca(2+)](i) rise. H(2)O(2) also triggered [Ca(2+)](i) rise.
      However, nifedipine-induced [Ca(2+)](i) increase was not affected by protamine.
      In conclusion, the present results indicate that 1) primary cultures of cells
      from terminal nephron of newborn rats are a useful tool for investigating Ca(2+)
      transport mechanisms during growth, and 2) newborn rat CCD cells in primary
      culture exhibit a new apical nifedipine-activated Ca(2+) channel of capacitive
      type (either transient receptor potential or leak channel).

PMID- 11287334
TI  - Influence of caveolin-1 on cellular cholesterol efflux mediated by high-density
      lipoproteins.
AB  - Caveolin-1 is a principal structural component of caveolae membranes. These
      membrane microdomains participate in the regulation of signaling, transcytosis,
      and cholesterol homeostasis at the plasma membrane. In the present study, we
      determined the effect of caveolin-1 expression on cellular cholesterol efflux
      mediated by high-density lipoprotein (HDL). We evaluated this effect in parental
      NIH/3T3 cells as well as in two transformed NIH/3T3 cell lines in which caveolin
      1 protein levels are dramatically downregulated. Compared with parental NIH/3T3
      cells, these two transformed cell lines effluxed cholesterol more rapidly to HDL.
      In addition, NIH/3T3 cells harboring caveolin-1 antisense also effluxed
      cholesterol more rapidly to HDL. However, this effect was not due to changes in
      total cellular cholesterol content. We further showed that chronic HDL exposure
      reduced caveolin-1 protein expression in NIH/3T3 cells. HDL exposure also
      inhibited caveolin-1 promoter activity, suggesting a direct negative effect of
      HDL on caveolin-1 gene transcription. Moreover, we showed that HDL-induced
      downregulation of caveolin-1 prevents the uptake of oxidized low-density
      lipoprotein in human endothelial cells. These data suggest a novel proatherogenic
      role for caveolin-1, i.e., regarding the uptake and/or transcytosis of modified
      lipoproteins.

PMID- 11287335
TI  - Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate
      cotransporter from mouse brain.
AB  - Neurons contain a high-affinity Na(+)/dicarboxylate cotransporter for absorption
      of neurotransmitter precursor substrates, such as alpha-ketoglutarate and malate,
      which are subsequently metabolized to replenish pools of neurotransmitters,
      including glutamate. We have isolated the cDNA coding for a high-affinity
      Na(+)/dicarboxylate cotransporter from mouse brain, called mNaDC-3. The mRNA
      coding for mNaDC-3 is found in brain and choroid plexus as well as in kidney and
      liver. The mNaDC-3 transporter has a broad substrate specificity for
      dicarboxylates, including succinate, alpha-ketoglutarate, fumarate, malate, and
      dimethylsuccinate. The transport of citrate is relatively insensitive to pH, but
      the transport of succinate is inhibited by acidic pH. The Michaelis-Menten
      constant for succinate in mNaDC-3 is 140 microM in transport assays and 16 microM
      at -50 mV in two-electrode voltage clamp assays. Transport is dependent on
      sodium, although lithium can partially substitute for sodium. In conclusion,
      mNaDC-3 likely codes for the high-affinity Na(+)/dicarboxylate cotransporter in
      brain, and it has some unusual electrical properties compared with the other
      members of the family.

PMID- 11287336
TI  - IFN-gamma downregulates expression of Na(+)/H(+) exchangers NHE2 and NHE3 in rat
      intestine and human Caco-2/bbe cells.
AB  - Diarrhea associated with inflammatory bowel diseases has traditionally been
      attributed to stimulated secretion. The purpose of this study was to determine
      whether chronic stimulation of intestinal mucosa by interferon-gamma (IFN-gamma)
      affects expression and function of the apical membrane Na(+)/H(+) exchangers NHE2
      and NHE3 in rat intestine and Caco-2/bbe (C2) cells. Confluent C2 cells
      expressing NHE2 and NHE3 were treated with IFN-gamma for 2, 24, and 48 h. Adult
      rats were injected with IFN-gamma intraperitoneally for 12 and 48 h. NHE2 and
      NHE3 activities were measured by unidirectional (22)Na influx across C2 cells and
      in rat brush-border membrane vesicles. NHE protein and mRNA were assessed by
      Western and Northern blotting. IFN-gamma treatment of C2 monolayers caused a >50%
      reduction in NHE2 and NHE3 activities and protein expression. In rats, region
      specific, time- and dose-dependent reductions of NHE2 and NHE3 activities,
      protein expression, and mRNA were observed after exposure to IFN-gamma. Chronic
      exposure of intestinal epithelial cells to IFN-gamma results in selective
      downregulation of NHE2 and NHE3 expression and activity, a potential cause of
      inflammation-associated diarrhea.

PMID- 11287337
TI  - Pertussis toxin directly activates endothelial cell p42/p44 MAP kinases via a
      novel signaling pathway.
AB  - Bordetella pertussis generates a bacterial toxin utilized in signal transduction
      investigation because of its ability to ADP ribosylate specific G proteins. We
      previously noted that pertussis toxin (PTX) directly activates endothelial cells,
      resulting in disruption of monolayer integrity and intercellular gap formation
      via a signaling pathway that involves protein kinase C (PKC). We studied the
      effect of PTX on the activity of the 42- and 44-kDa extracellular signal
      regulated kinases (ERK), members of a kinase family known to be activated by PKC.
      PTX caused a rapid time-dependent increase in bovine pulmonary artery endothelial
      cell ERK activity that was significantly attenuated by 1) pharmacological
      inhibition of MEK, the upstream ERK activating kinase, 2) an MEK dominant
      negative construct, and 3) PKC inhibition with bisindolylmaleimide. There was
      little evidence for the involvement of either Gbetagamma-subunits, Ras GTPases,
      Raf-1, p60(src), or phosphatidylinositol 3'-kinases in PTX-mediated ERK
      activation. Both the purified beta-oligomer binding subunit of the PTX holotoxin
      and a PTX holotoxin mutant genetically engineered to eliminate intrinsic ADP
      ribosyltransferase activity completely reproduced PTX effects on ERK activation,
      suggesting that PTX-induced ERK activation involves a novel PKC-dependent
      signaling mechanism that is independent of either Ras or Raf-1 activities and
      does not require G protein ADP ribosylation.

PMID- 11287338
TI  - Evaluation of islet heme oxygenase-CO and nitric oxide synthase-NO pathways
      during acute endotoxemia.
AB  - We investigated, by a combined in vivo and in vitro approach, the temporal
      changes of islet nitric oxide synthase (NOS)-derived nitric oxide (NO) and heme
      oxygenase (HO)-derived carbon monoxide (CO) production in relation to insulin and
      glucagon secretion during acute endotoxemia induced by lipopolysaccharide (LPS)
      in mice. Basal plasma glucagon, islet cAMP and cGMP content after in vitro
      incubation, the insulin response to glucose in vivo and in vitro, and the insulin
      and glucagon responses to the adenylate cyclase activator forskolin were greatly
      increased after LPS. Immunoblots demonstrated expression of inducible NOS (iNOS),
      inducible HO (HO-1), and an increased expression of constitutive HO (HO-2) in
      islet tissue. Immunocytochemistry revealed a marked expression of iNOS in many
      beta-cells, but only in single alpha-cells after LPS. Moreover, biochemical
      analysis showed a time dependent and markedly increased production of NO and CO
      in these islets. Addition of a NOS inhibitor to such islets evoked a marked
      potentiation of glucose-stimulated insulin release. Finally, after incubation in
      vitro, a marked suppression of NO production by both exogenous CO and glucagon
      was observed in control islets. This effect occurred independently of a
      concomitant inhibition of guanylyl cyclase. We suggest that the impairing effect
      of increased production of islet NO on insulin secretion during acute endotoxemia
      is antagonized by increased activities of the islet cAMP and HO-CO systems,
      constituting important compensatory mechanisms against the noxious and
      diabetogenic actions of NO in endocrine pancreas.

PMID- 11287339
TI  - Differential effects of growth hormone and insulin-like growth factor I on human
      endothelial cell migration.
AB  - Effects of growth hormone (GH), insulin-like growth factor I (IGF-I), and
      endothelin-1 (ET-1) on endothelial cell migration and the underlying molecular
      mechanisms were explored using a human umbilical cord endothelial cell line,
      ECV304 cells, in vitro. Treatment of the cells with IGF-I or ET-1, but not GH,
      stimulated the cell migration. Interestingly, however, ET-1-induced, but not IGF
      I-induced, migration of the cells was inhibited by GH. Both ET-1 and IGF-I caused
      activation of mitogen-activated protein kinase (MAPK) in the cells, and GH
      eliminated the MAPK activation produced by ET-1 but not that produced by IGF-I.
      On the other hand, migration of the cells was stimulated by protein kinase C
      (PKC) agonist, phorbol 12-myristate 13-acetate. ET-1 promoted PKC activity, and a
      PKC inhibitor, GF-109203X, blocked ET-1-induced cell migration. Although GH
      inhibited ET-1-induced cell migration and MAPK activity, it did not block ET-1
      induced PKC activation. Thus ET-1 stimulation of endothelial cell migration
      appears to be mediated by PKC/MAPK pathway, and GH may inhibit the MAPK
      activation by ET-1 at the downstream of PKC.

PMID- 11287340
TI  - In vivo regulation of the beta-myosin heavy chain gene in hypertensive rodent
      heart.
AB  - The main goal of this study was to examine the transcriptional activity of
      different-length beta-myosin heavy chain (beta-MHC) promoters in the hypertensive
      rodent heart using the direct gene transfer approach. A hypertensive state was
      induced by abdominal aortic constriction (AbCon) sufficient to elevate mean
      arterial pressure by approximately 45% relative to control. Results show that
      beta-MHC promoter activity of all tested wild-type constructs, i.e., -3500, -408,
      -299, -215, -171, and -71 bp, was significantly increased in AbCon hearts. In the
      normal control hearts, expression of the -71-bp construct was comparable to that
      of the promoterless vector, but its induction by AbCon was comparable to that of
      the other constructs. Additional results, based on mutation analysis and DNA gel
      mobility shift assays targeting betae1, betae2, GATA, and betae3 elements, show
      that these previously defined cis-elements in the proximal promoter are indeed
      involved in maintaining basal promoter activity; however, none of these elements,
      either individually or collectively, appear to be major players in mediating the
      hypertension response of the beta-MHC gene. Collectively, these results indicate
      that three separate regions on the beta-MHC promoter are involved in the
      induction of the gene in response to hypertension: 1) a distal region between 
      408 and -3500 bp, 2) a proximal region between -299 and -215 bp, and 3) a basal
      region within -71 bp of the transcription start site. Future research needs to
      further characterize these responsive regions to more fully delineate beta-MHC
      transcriptional regulation in response to pressure overload.

PMID- 11287341
TI  - Overexpression of stomatin depresses GLUT-1 glucose transporter activity.
AB  - We showed previously that GLUT-1 glucose transporter is associated with stomatin
      (band 7.2b) in human red blood cell membranes and in Clone 9 cells. We show here
      that in a mixed population of stably transfected cells, overexpression of either
      murine or human stomatin resulted in 35-50% reduction in the basal rate of
      glucose transport. Moreover, there was a correlation between increased expression
      of stomatin and depression in the rate of glucose transport. In two clones chosen
      for further study, the ~10% and ~70% reduction in basal rate of glucose transport
      was associated with increases in stomatin mRNA and protein expression without a
      detectable change in GLUT-1 content in plasma membranes of either clone. In the
      clone overexpressing high levels of stomatin, immunoprecipitated GLUT-1 was
      associated with a large amount of stomatin as a coimmunoprecipitant. Employing
      extracts of cells overexpressing human stomatin, we found that stomatin bound to
      the glutathione-S-transferase (GST) fusion protein containing the COOH-terminal
      42-amino acid segment of GLUT-1 but not to GST alone or a GST fusion protein
      containing the 66-amino acid central loop of GLUT-1. Rat stomatin cDNA was cloned
      by RT-PCR and found to be highly homologous to mouse (97%) and human (86%)
      stomatins. These results suggest that overexpression of stomatin results in a
      depression in the basal rate of glucose transport by decreasing the "intrinsic"
      activity of GLUT-1, probably through protein-protein interaction.

PMID- 11287342
TI  - A store-operated nonselective cation channel in lymphocytes is activated directly
      by Ca(2+) influx factor and diacylglycerol.
AB  - Agonist-receptor interactions at the plasma membrane often lead to activation of
      store-operated channels (SOCs) in the plasma membrane, allowing for sustained
      Ca(2+) influx. While Ca(2+) influx is important for many biological processes,
      little is known about the types of SOCs, the nature of the depletion signal, or
      how the SOCs are activated. We recently showed that in addition to the Ca(2+)
      release-activated Ca(2+) (CRAC) channel, both Jurkat T cells and human peripheral
      blood mononuclear cells express novel store-operated nonselective cation channels
      that we termed Ca(2+) release-activated nonselective cation (CRANC) channels.
      Here we demonstrate that activation of both CRAC and CRANC channels is
      accelerated by a soluble Ca(2+) influx factor (CIF). In addition, CRANC channels
      in inside-out plasma membrane patches are directly activated upon exposure of
      their cytoplasmic side to highly purified CIF preparations. Furthermore, CRANC
      channels are also directly activated by diacylglycerol. These results strongly
      suggest that the Ca(2+) store-depletion signal is a diffusible molecule and that
      at least some SOCs may have dual activation mechanisms.

PMID- 11287343
TI  - Arachidonic acid both inhibits and enhances whole cell calcium currents in rat
      sympathetic neurons.
AB  - We recently reported that arachidonic acid (AA) inhibits L- and N-type Ca(2+)
      currents at positive test potentials in the presence of the dihydropyridine L
      type Ca(2+) channel agonist (+)-202-791 in dissociated neonatal rat superior
      cervical ganglion neurons [Liu L and Rittenhouse AR. J Physiol (Lond) 525: 291
      404, 2000]. In this first of two companion papers, we characterized the mechanism
      of inhibition by AA at the whole cell level. In the presence of either omega
      conotoxin GVIA or nimodipine, AA decreased current amplitude, confirming that L-
      and N-type currents, respectively, were inhibited. AA-induced inhibition was
      concentration dependent and reversible with an albumin-containing wash solution,
      but appears independent of AA metabolism and G protein activity. In
      characterizing inhibition, an AA-induced enhancement of current amplitude was
      revealed that occurred primarily at negative test potentials. Cell dialysis with
      albumin minimized inhibition but had little effect on enhancement, suggesting
      that AA has distinct sites of action. We examined AA's actions on current
      kinetics and found that AA increased holding potential-dependent inactivation. AA
      also enhanced the rate of N-type current activation. These findings indicate that
      AA causes multiple changes in sympathetic Ca(2+) currents.

PMID- 11287344
TI  - Arachidonic acid reversibly enhances N-type calcium current at an extracellular
      site.
AB  - We examined the effects of arachidonic acid (AA) on whole cell Ca(2+) channel
      activity in rat superior cervical ganglion neurons. Our companion paper (Liu L,
      Barrett CF, and Rittenhouse AR. Am J Physiol Cell Physiol 280: C1293-C1305, 2001)
      demonstrates that AA induces several effects, including enhancement of current
      amplitude at negative voltages, and increased activation kinetics. This study
      examines the mechanisms underlying these effects. First, enhancement is rapidly
      reversible by bath application of BSA. Second, enhancement appears to occur
      extracellularly, since intracellular albumin was without effect on enhancement,
      and bath-applied arachidonoyl coenzyme A, an amphiphilic AA analog that cannot
      cross the cell membrane, mimicked enhancement. In addition, enhancement is
      voltage dependent, in that currents were enhanced to the greatest degree at -10
      mV, whereas virtually no enhancement occurred positive of +30 mV. We also
      demonstrate that AA-induced increases in activation kinetics are correlated with
      enhancement of current amplitude. An observed increase in the voltage sensitivity
      may underlie these effects. Finally, the majority of enhancement is mediated
      through N-type current, thus providing the first demonstration that this current
      type can be enhanced by AA.

PMID- 11287345
TI  - Mouse MCT3 gene is expressed preferentially in retinal pigment and choroid plexus
      epithelia.
AB  - Monocarboxylate transporters (MCTs) are a family of highly homologous membrane
      proteins that mediate the 1:1 transport of a proton and a lactate ion. In
      chicken, MCT3 is preferentially expressed in the retinal pigment epithelium
      (RPE). We have isolated the mouse MCT3 cDNA and gene and characterized the
      pattern of tissue expression. MCT3 is a single copy gene with a 1.8-kb transcript
      that encodes a protein with a predicted molecular mass of 51.5 kDa. Based on
      Northern hybridization analysis, MCT3 transcript was expressed in only two
      tissues: RPE and choroid plexus epithelium (CPE). The choroid plexus forms a
      barrier between the cerebrospinal fluid and fenestrated capillaries, similar to
      the organization of the RPE and choroidal vessels. Immunohistochemical staining
      demonstrated that MCT3 was restricted to the basolateral membranes of both
      epithelia but was more abundant in RPE than CPE. Differences in the level of
      protein expression were confirmed by Western blot analysis. The cloning of MCT3
      identifies a specific transporter that could regulate lactate levels in fluid
      bathing neuronal tissues.

PMID- 11287346
TI  - Molecular identification of a TTX-sensitive Ca(2+) current.
AB  - The TTX-sensitive Ca(2+) current [I(Ca(TTX))] observed in cardiac myocytes under
      Na(+)-free conditions was investigated using patch-clamp and Ca(2+)-imaging
      methods. Cs(+) and Ca(2+) were found to contribute to I(Ca(TTX)), but TEA(+) and
      N-methyl-D-glucamine (NMDG(+)) did not. HEK-293 cells transfected with cardiac
      Na(+) channels exhibited a current that resembled I(Ca(TTX)) in cardiac myocytes
      with regard to voltage dependence, inactivation kinetics, and ion selectivity,
      suggesting that the cardiac Na(+) channel itself gives rise to I(Ca(TTX)).
      Furthermore, repeated activation of I(Ca(TTX)) led to a 60% increase in
      intracellular Ca(2+) concentration, confirming Ca(2+) entry through this current.
      Ba(2+) permeation of I(Ca(TTX)), reported by others, did not occur in rat
      myocytes or in HEK-293 cells expressing cardiac Na(+) channels under our
      experimental conditions. The report of block of I(Ca(TTX)) in guinea pig heart by
      mibefradil (10 microM) was supported in transfected HEK-293 cells, but Na(+)
      current was also blocked (half-block at 0.45 microM). We conclude that I(Ca(TTX))
      reflects current through cardiac Na(+) channels in Na(+)-free (or "null")
      conditions. We suggest that the current be renamed I(Na(null)) to more accurately
      reflect the molecular identity of the channel and the conditions needed for its
      activation. The relationship between I(Na(null)) and Ca(2+) flux through slip
      mode conductance of cardiac Na(+) channels is discussed in the context of ion
      channel biophysics and "permeation plasticity."

PMID- 11287347
TI  - Model organisms: new insights into ion channel and transporter function. Stomatin
      homologues interact in Caenorhabditis elegans.
AB  - In C. elegans the protein UNC-1 is a major determinant of anesthetic sensitivity
      and is a close homologue of the mammalian protein stomatin. In humans stomatin is
      missing from erythrocyte membranes in the hemolytic disease overhydrated
      hereditary stomatocytosis, despite an apparently normal stomatin gene.
      Overhydrated hereditary stomatocytosis is characterized by alteration of the
      normal transmembrane gradients of sodium and potassium. Stomatin has been shown
      to interact genetically with sodium channels. It is also postulated that stomatin
      is important in the organization of lipid rafts. We demonstrate here that
      antibodies against UNC-1 stain the major nerve tracts of Caenorhabditis elegans,
      with very intense staining of the nerve ring. We also found that a gene encoding
      a stomatin-like protein, UNC-24, affects anesthetic sensitivity and is
      genetically epistatic to unc-1. In the absence of UNC-24, the staining of the
      nerve ring by anti-UNC-1 is abolished, despite normal transcriptional levels of
      the unc-1 mRNA. Western blots indicate that UNC-24 probably affects the stability
      of the UNC-1 protein. UNC-24 may therefore be necessary for the correct placement
      of UNC-1 in the cell membrane and organization of lipid rafts.

PMID- 11287348
TI  - Role of IP(3) in modulation of spontaneous activity in pacemaker cells of rabbit
      urethra.
AB  - Isolated interstitial ("pacemaker") cells from rabbit urethra were examined using
      the perforated-patch technique. Under voltage clamp at -60 mV, these cells fired
      large spontaneous transient inward currents (STICs), averaging -860 pA and >1 s
      in duration, which could account for urethral pacemaker activity. Spontaneous
      transient outward currents (STOCs) were also observed and fell into two
      categories, "fast" (<100 ms in duration) and "slow" (>1 s in duration). The
      latter were coupled to STICs, suggesting that they shared the same mechanism,
      while the former occurred independently at faster rates. All of these currents
      were abolished by cyclopiazonic acid, caffeine, or ryanodine, suggesting that
      they were activated by Ca(2+) release. When D-myo-inositol 1,4,5-trisphosphate
      (IP(3))-sensitive stores were blocked with 2-aminoethoxydiphenyl borate, the
      STICs and slow STOCs were abolished, but the fast STOCs remained. In contrast,
      the fast STOCs were more nifedipine sensitive than the STICs or the slow STOCs.
      These results suggest that while fast STOCs are mediated by a mechanism similar
      to STOCs in smooth muscle, STICs and slow STOCs are driven by IP(3). These
      results support the hypothesis that pacemaker activity in the urethra is driven
      by the IP(3)-sensitive store.

PMID- 11287349
TI  - AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle.
AB  - The AMP-activated protein kinase (AMPK) has been hypothesized to mediate
      contraction and 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR)
      induced increases in glucose uptake in skeletal muscle. The purpose of the
      current study was to determine whether treadmill exercise and isolated muscle
      contractions in rat skeletal muscle increase the activity of the AMPK alpha 1 and
      AMPK alpha 2 catalytic subunits in a dose-dependent manner and to evaluate the
      effects of the putative AMPK inhibitors adenine 9-beta-D-arabinofuranoside (ara
      A), 8-bromo-AMP, and iodotubercidin on AMPK activity and 3-O-methyl-D-glucose (3
      MG) uptake. There were dose-dependent increases in AMPK alpha 2 activity and 3-MG
      uptake in rat epitrochlearis muscles with treadmill running exercise but no
      effect of exercise on AMPK alpha1 activity. Tetanic contractions of isolated
      epitrochlearis muscles in vitro significantly increased the activity of both AMPK
      isoforms in a dose-dependent manner and at a similar rate compared with increases
      in 3-MG uptake. In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo
      AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPK alpha 2 activity
      and 3-MG uptake but had little effect on AMPK alpha 1 activity. In contrast,
      these compounds had absent or minimal effects on contraction-stimulated AMPK
      alpha 1 and -alpha 2 activity and 3-MG uptake. Although the AMPK alpha 1 and 
      alpha 2 isoforms are activated during tetanic muscle contractions in vitro, in
      fast-glycolytic fibers, the activation of AMPK alpha 2-containing complexes may
      be more important in regulating exercise-mediated skeletal muscle metabolism in
      vivo. Development of new compounds will be required to study contraction
      regulation of AMPK by pharmacological inhibition.

PMID- 11287350
TI  - Activation of NADPH oxidase by AGE links oxidant stress to altered gene
      expression via RAGE.
AB  - Engagement of the receptor for advanced glycation end products (RAGE) by products
      of nonenzymatic glycation/oxidation triggers the generation of reactive oxygen
      species (ROS), thereby altering gene expression. Because dissection of the
      precise events by which ROS are generated via RAGE is relevant to the
      pathogenesis of complications in AGE-related disorders, such as diabetes and
      renal failure, we tested the hypothesis that activation of NADPH oxidase
      contributed, at least in part, to enhancing oxidant stress via RAGE. Here we show
      that incubation of human endothelial cells with AGEs on the surface of diabetic
      red blood cells, or specific AGEs, (carboxymethyl)lysine (CML)-modified adducts,
      prompted intracellular generation of hydrogen peroxide, cell surface expression
      of vascular cell adhesion molecule-1, and generation of tissue factor in a manner
      suppressed by treatment with diphenyliodonium, but not by inhibitors of nitric
      oxide. Consistent with an important role for NADPH oxidase, although macrophages
      derived from wild-type mice expressed enhanced levels of tissue factor upon
      stimulation with AGE, macrophages derived from mice deficient in a central
      subunit of NADPH oxidase, gp91phox, failed to display enhanced tissue factor in
      the presence of AGE. These findings underscore a central role of NADPH oxidase in
      AGE-RAGE-mediated generation of ROS and provide a mechanism for altered gene
      expression in AGE-related disorders.

PMID- 11287351
TI  - A high-sucrose diet increases gluconeogenic capacity in isolated periportal and
      perivenous rat hepatocytes.
AB  - A high-sucrose (SU) diet increases gluconeogenesis (GNG) in the liver. The
      present study was conducted to determine the contribution of periportal (PP) and
      perivenous (PV) cell populations to this SU-induced increase in GNG. Male Sprague
      Dawley rats were fed an SU (68% sucrose) or starch (ST, 68% starch) diet for 1
      wk, and hepatocytes were isolated from the PP or PV region of the liver acinus.
      Hepatocytes were incubated for 1 h in the presence of various gluconeogenic
      substrates, and glucose release into the medium was used to estimate GNG. When
      incubated in the presence of 5 mM lactate, which enters GNG at the level of
      pyruvate, glucose release (nmol x h(-1) x mg(-1)) was significantly increased by
      the SU diet in both PP (84.8 +/- 3.4 vs. 70.4 +/- 2.6) and PV (64.3 +/- 2.5 vs.
      38.2 +/- 2.1) cells. Addition of palmitate (0.5 mM) increased glucose release
      from lactate in PP cells by 11.6 +/- 0.5 and 20.6 +/- 1.5% and in PV cells by
      11.0 +/- 4.4 and 51.1 +/- 9.1% in SU and ST, respectively. When cells were
      incubated with 5 mM dihydroxyacetone (DHA), which enters GNG at the
      triosephosphate level, glucose release was significantly increased by the SU diet
      in both cell types. In contrast, glucose release from fructose (0.5 mM) was
      significantly increased by the SU diet in PV cells only. These changes in glucose
      release were accompanied by significant increases in the maximal specific
      activities of glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate
      carboxykinase (PEPCK) in both PP and PV cells. These data suggest that the SU
      diet influences GNG in both PP and PV cell populations. It appears that SU
      feeding produces changes in GNG via alterations in at least two critical enzymes,
      G-6-Pase and PEPCK.

PMID- 11287352
TI  - Fructose augments infection-impaired net hepatic glucose uptake during TPN
      administration.
AB  - During chronic total parenteral nutrition (TPN), net hepatic glucose uptake
      (NHGU) and net hepatic lactate release (NHLR) are markedly reduced (downward
      arrow approximately 45 and approximately 65%, respectively) with infection.
      Because small quantities of fructose are known to augment hepatic glucose uptake
      and lactate release in normal fasted animals, the aim of this work was to
      determine whether acute fructose infusion with TPN could correct the impairments
      in NHGU and NHLR during infection. Chronically catheterized conscious dogs
      received TPN for 5 days via the inferior vena cava at a rate designed to match
      daily basal energy requirements. On the third day of TPN administration, a
      sterile (SHAM, n = 12) or Escherichia coli-containing (INF, n = 11) fibrin clot
      was implanted in the peritoneal cavity. Forty-two hours later, somatostatin was
      infused with intraportal replacement of insulin (12 +/- 2 vs. 24 +/- 2 microU/ml,
      SHAM vs. INF, respectively) and glucagon (24 +/- 4 vs. 92 +/- 5 pg/ml) to match
      concentrations previously observed in sham and infected animals. After a 120-min
      basal period, animals received either saline (Sham+S, n = 6; Inf+S, n = 6) or
      intraportal fructose (0.7 mg x kg(-1) x min(-1); Sham+F, n = 6; Inf+F, n = 5)
      infusion for 180 min. Isoglycemia of 120 mg/dl was maintained with a variable
      glucose infusion. Combined tracer and arteriovenous difference techniques were
      used to assess hepatic glucose metabolism. Acute fructose infusion with TPN
      augmented NHGU by 2.9 +/- 0.4 and 2.5 +/- 0.3 mg x kg(-1) x min(-1) in Sham+F and
      Inf+F, respectively. The majority of liver glucose uptake was stored as glycogen,
      and NHLR did not increase substantially. Therefore, despite an infection-induced
      impairment in NHGU and different hormonal environments, small amounts of fructose
      enhanced NHGU similarly in sham and infected animals. Glycogen storage, not
      lactate release, was the preferential fate of the fructose-induced increase in
      hepatic glucose disposal in animals adapted to TPN.

PMID- 11287353
TI  - Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase
      activity and glycogen synthesis.
AB  - Although chronic hyperinsulinemia has been shown to induce insulin resistance,
      the basic cellular mechanisms responsible for this phenomenon are unknown. The
      present study was performed 1) to determine the time-related effect of
      physiological hyperinsulinemia on glycogen synthase (GS) activity, hexokinase II
      (HKII) activity and mRNA content, and GLUT-4 protein in muscle from healthy
      subjects, and 2) to relate hyperinsulinemia-induced alterations in these
      parameters to changes in glucose metabolism in vivo. Twenty healthy subjects had
      a 240-min euglycemic insulin clamp study with muscle biopsies and then received a
      low-dose insulin infusion for 24 (n = 6) or 72 h (n = 14) (plasma insulin
      concentration = 121 +/- 9 or 143 +/- 25 pmol/l, respectively). During the
      baseline insulin clamp, GS fractional velocity (0.075 +/- 0.008 to 0.229 +/-
      0.02, P < 0.01), HKII mRNA content (0.179 +/- 0.034 to 0.354 +/- 0.087, P <
      0.05), and HKII activity (2.41 +/- 0.63 to 3.35 +/- 0.54 pmol x min(-1) x ng(-1),
      P < 0.05), as well as whole body glucose disposal and nonoxidative glucose
      disposal, increased. During the insulin clamp performed after 24 and 72 h of
      sustained physiological hyperinsulinemia, the ability of insulin to increase
      muscle GS fractional velocity, total body glucose disposal, and nonoxidative
      glucose disposal was impaired (all P < 0.01), whereas the effect of insulin on
      muscle HKII mRNA, HKII activity, GLUT-4 protein content, and whole body rates of
      glucose oxidation and glycolysis remained unchanged. Muscle glycogen
      concentration did not change [116 +/- 28 vs. 126 +/- 29 micromol/kg muscle, P =
      nonsignificant (NS)] and was not correlated with the change in nonoxidative
      glucose disposal (r = 0.074, P = NS). In summary, modest chronic hyperinsulinemia
      may contribute directly (independent of change in muscle glycogen concentration)
      to the development of insulin resistance by its impact on the GS pathway.

PMID- 11287354
TI  - Insulin secretion and IP levels in two distant lineages of the genus Mus:
      comparisons with rat islets.
AB  - Islet responses of two different Mus geni, the laboratory mouse (Mus musculus)
      and a phylogenetically more ancient species (Mus caroli), were measured and
      compared with the responses of islets from rats (Rattus norvegicus). A minimal
      and flat second-phase response to 20 mM glucose was evoked from M. musculus
      islets, whereas a large rising second-phase response characterized rat islets. M.
      caroli responses were intermediate between these two extremes; a modest rising
      second-phase response to 20 mM glucose was observed. Prior, brief stimulation of
      rat islets with 20 mM glucose results in an amplified insulin secretory response
      to a subsequent 20 mM glucose challenge. No such potentiation or priming was
      observed from M. musculus islets. In contrast, M. caroli islets displayed a
      modest twofold potentiated first-phase response upon subsequent restimulation
      with 20 mM glucose. Inositol phosphate (IP) accumulation in response to 20 mM
      glucose stimulation in [(3)H]inositol-prelabeled rat or mouse islets paralleled
      the insulin secretory responses. The divergence in 20 mM glucose-induced insulin
      release between these species may be attributable to differences in phospholipase
      C-mediated IP accumulation in islets.

PMID- 11287355
TI  - Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex
      specific effects.
AB  - Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on days
      40--41, days 50--51, and days 60--61 of gestation. Adult offspring were split
      into two groups. Group 1 guinea pigs were catheterized, and the hypothalamo
      pituitary-adrenal (HPA) axis was tested in basal and activated states. Group 2
      guinea pigs were euthanized with no further manipulation. In male offspring,
      prenatal dexamethasone exposure resulted in a significant reduction in brain-to
      body weight ratio. Dexamethasone-exposed male offspring exhibited reduced basal
      and activated plasma cortisol levels, which was associated with elevated
      hippocampal mineralocorticoid receptor (MR) mRNA and increased plasma
      testosterone. In females exposed to glucocorticoids in utero, basal and
      stimulated plasma cortisol levels were higher in the follicular and early luteal
      phases of the cycle, but this effect was reversed in the late luteal phase,
      indicating a significant interaction of sex steroids. In female offspring (at
      estrus), glucocorticoid receptor mRNA levels were lower in the paraventricular
      nucleus and pars distalis but higher in the hippocampus in animals exposed to
      dexamethasone in utero. Hippocampal MR mRNA levels were significantly lower
      (approximately 50%) than in controls. In conclusion, repeated antenatal
      glucocorticoid treatment programs HPA function in a sex-specific manner, and
      these changes are associated with modification of corticosteroid receptor
      expression in the adult brain and pituitary.

PMID- 11287356
TI  - Direct evidence for tonic sympathetic support of resting metabolic rate in
      healthy adult humans.
AB  - The sympathetic nervous system (SNS) plays an important role in the regulation of
      energy expenditure. However, whether tonic SNS activity contributes to resting
      metabolic rate (RMR) in healthy adult humans is controversial, with the majority
      of studies showing no effect. We hypothesized that an intravenous propranolol
      infusion designed to achieve complete beta-adrenergic blockade would result in a
      significant acute decrease in RMR in healthy adults. RMR (ventilated hood,
      indirect calorimetry) was measured in 29 healthy adults (15 males, 14 females)
      before and during complete beta-adrenergic blockade documented by plasma
      propranolol concentrations > or =100 ng/ml, lack of heart rate response to
      isoproterenol, and a plateau in RMR with increased doses of propranolol.
      Propranolol infusion evoked an acute decrease in RMR (-71 +/- 11 kcal/day; -5 +/-
      0.7%, P < 0.0001), whereas RMR was unchanged from baseline levels during a saline
      control infusion (P > 0.05). The response to propranolol differed from the
      response to saline control (P < 0.01). The absolute and percent decreases in RMR
      with propranolol were modestly related to baseline plasma concentration of
      norepinephrine (r = 0.38, P = 0.05; r = 0.44, P = 0.02, respectively). These
      findings provide direct evidence for the concept of tonic sympathetic beta
      adrenergic support of RMR in healthy nonobese adults.

PMID- 11287357
TI  - Adipose tissue tumor necrosis factor and interleukin-6 expression in human
      obesity and insulin resistance.
AB  - Adipose tissue expresses tumor necrosis factor (TNF) and interleukin (IL)-6,
      which may cause obesity-related insulin resistance. We measured TNF and IL-6
      expression in the adipose tissue of 50 lean and obese subjects without diabetes.
      Insulin sensitivity (S(I)) was determined by an intravenous glucose tolerance
      test with minimal-model analysis. When lean [body mass index (BMI) <25 kg/m(2)]
      and obese (BMI 30-40 kg/m(2)) subjects were compared, there was a 7.5-fold
      increase in TNF secretion (P < 0.05) from adipose tissue, and the TNF secretion
      was inversely related to S(I) (r = -0.42, P < 0.02). IL-6 was abundantly
      expressed by adipose tissue. In contrast to TNF, plasma (rather than adipose) IL
      6 demonstrated the strongest relationship with obesity and insulin resistance.
      Plasma IL-6 was significantly higher in obese subjects and demonstrated a highly
      significant inverse relationship with S(I) (r = -0.71, P < 0.001). To separate
      the effects of BMI from S(I), subjects who were discordant for S(I) were matched
      for BMI, age, and gender. By use of this approach, subjects with low S(I)
      demonstrated a 3.0-fold increased level of TNF secretion from adipose tissue and
      a 2.3-fold higher plasma IL-6 level (P < 0.05) compared with matched subjects
      with a high S(I). Plasma IL-6 was significantly associated with plasma
      nonesterified fatty acid levels (r = 0.49, P < 0.002). Thus the local expression
      of TNF and plasma IL-6 are higher in subjects with obesity-related insulin
      resistance.

PMID- 11287358
TI  - Effects of beta-adrenergic receptor stimulation and blockade on substrate
      metabolism during submaximal exercise.
AB  - We used beta-adrenergic receptor stimulation and blockade as a tool to study
      substrate metabolism during exercise. Eight moderately trained subjects cycled
      for 60 min at 45% of VO(2 peak) 1) during a control trial (CON); 2) while
      epinephrine was intravenously infused at 0.015 microg. kg(-1) x min(-1) (beta
      STIM); 3) after ingesting 80 mg of propranolol (beta-BLOCK); and 4) combining
      beta-BLOCK with intravenous infusion of Intralipid-heparin to restore plasma
      fatty acid (FFA) levels (beta-BLOCK+LIPID). beta-BLOCK suppressed lipolysis
      (i.e., glycerol rate of appearance) and fat oxidation while elevating
      carbohydrate oxidation above CON (135 +/- 11 vs. 113 +/- 10 micromol x kg(-1) x
      min(-1); P < 0.05) primarily by increasing rate of disappearance (R(d)) of
      glucose (36 +/- 2 vs. 22 +/- 2 micromol x kg(-1) x min(-1); P < 0.05). Plasma FFA
      restoration (beta-BLOCK+LIPID) attenuated the increase in R(d) glucose by more
      than one-half (28 +/- 3 micromol x kg(-1) x min(-1); P < 0.05), suggesting that
      part of the compensatory increase in muscle glucose uptake is due to reduced
      energy from fatty acids. On the other hand, beta-STIM markedly increased glycogen
      oxidation and reduced glucose clearance and fat oxidation despite elevating
      plasma FFA. Therefore, reduced plasma FFA availability with beta-BLOCK increased
      R(d) glucose, whereas beta-STIM increased glycogen oxidation, which reduced fat
      oxidation and glucose clearance. In summary, compared with control exercise at
      45% VO(2 peak) (CON), both beta-BLOCK and beta-STIM reduced fat and increased
      carbohydrate oxidation, albeit through different mechanisms.

PMID- 11287359
TI  - T(3) increases mitochondrial ATP production in oxidative muscle despite increased
      expression of UCP2 and -3.
AB  - Triiodothyronine (T(3)) increases O(2) and nutrient flux through mitochondria
      (Mito) of many tissues, but it is unclear whether ATP synthesis is increased,
      particularly in different types of skeletal muscle, because variable changes in
      uncoupling proteins (UCP) and enzymes have been reported. Thus Mito ATP
      production was measured in oxidative and glycolytic muscles, as well as in liver
      and heart, in rats administered T(3) for 14 days. Relative to saline-treated
      controls, T(3) rats had 80, 168, and 62% higher ATP production in soleus muscle,
      liver, and heart, respectively, as well as higher activities of citrate synthase
      (CS; 63, 90, 25%) and cytochrome c oxidase (COX; 119, 225, 52%) in the same
      tissues (all P < 0.01). In plantaris muscle of T(3) rats, CS was only slightly
      higher (17%, P < 0.05) than in controls, and ATP production and COX were
      unaffected. mRNA levels of COX I and III were 33 and 47% higher in soleus of T(3)
      rats (P < 0.01), but there were no differences in plantaris. In contrast, UCP2
      and -3 mRNAs were 2.5- to 14-fold higher, and protein levels were 3- to 10-fold
      higher in both plantaris and soleus of the T(3) group. We conclude that T(3)
      increases oxidative enzymes and Mito ATP production and Mito-encoded transcripts
      in oxidative but not glycolytic rodent tissues. Despite large increases in UCP
      expression, ATP production was enhanced in oxidative tissues and maintained in
      glycolytic muscle of hyperthyroid rats.

PMID- 11287360
TI  - Differential effects of insulin on peripheral and visceral tissue protein
      synthesis in neonatal pigs.
AB  - We recently demonstrated in neonatal pigs that, with amino acids and glucose
      maintained at fasting levels, the stimulation of protein synthesis in longissimus
      dorsi muscle with feeding can be reproduced by a physiological rise in insulin
      alone. In the current report, we determine whether the response of protein
      synthesis to insulin in the neonatal pig is 1) present in muscles of different
      fiber types, 2) proportional in myofibrillar and sarcoplasmic proteins, 3)
      associated with increased translational efficiency and ribosome number, and 4)
      present in other peripheral tissues and in viscera. Hyperinsulinemic-euglycemic
      amino acid clamps were performed in 7- and 26-day-old pigs infused with 0, 30,
      100, or 1,000 ng. kg(-0.66). min(-1) of insulin to reproduce insulin levels
      present in fasted, fed, refed, and supraphysiological conditions, respectively.
      Tissue protein synthesis was measured using a flooding dose of L-[4
      (3)H]phenylalanine. Insulin increased protein synthesis in gastrocnemius muscle
      and, to a lesser degree, masseter muscle. The degree of stimulation of protein
      synthesis by insulin was similar in myofibrillar and sarcoplasmic proteins.
      Insulin increased translational efficiency but had no effect on ribosome number
      in muscle. All of these insulin-induced changes in muscle protein synthesis
      decreased with age. Insulin also stimulated protein synthesis in cardiac muscle
      and skin but not in liver, intestine, spleen, pancreas, or kidney. The results
      support the hypothesis that insulin mediates the feeding-induced stimulation of
      myofibrillar and sarcoplasmic protein synthesis in muscles of different fiber
      types in the neonate by increasing the efficiency of translation. However,
      insulin does not appear to be involved in the feeding-induced stimulation of
      protein synthesis in visceral tissues. Thus different mechanisms regulate the
      growth of peripheral and visceral tissues in the neonate.

PMID- 11287361
TI  - Involvement of upstream open reading frames in regulation of rat V(1b)
      vasopressin receptor expression.
AB  - The V(1b) vasopressin receptor, expressed mainly in the corticotroph of the
      anterior pituitary, mediates the stimulatory effect of vasopressin on ACTH
      release. To clarify the regulation of receptor expression, we cloned, sequenced
      (up to approximately 5 kb from the translation start site), and characterized the
      5'-flanking region of the rat V(1b) receptor gene. We identified the
      transcription start site by amplification of cDNA ends and found a new intron
      within the 5'-untranslated region (5'-UTR) by comparing the sequence with that of
      cDNA. We then confirmed that the obtained promoter indeed has transcriptional
      activity by use of the luciferase reporter in AtT-20 mouse corticotroph cells.
      Interestingly, there were five short upstream open reading frames (uORFs) located
      within the 5'-UTR that were found to suppress V(1b) expression. Subsequent
      mutational analyses showed that the two downstream uORFs have an inhibitory
      effect on expression in both homologous and heterologous contexts. Furthermore,
      the inhibition did not accompany a parallel decrease in mRNA, suggesting that the
      suppressive effect occurs at a level downstream of transcription. Taken together,
      our data strongly suggest that the expression of the V(1b) receptor is regulated
      at the posttranscriptional as well as transcriptional level through uORFs within
      the 5'-UTR region of the mRNA. Whether the uORF-mediated regulation of V(1b)
      expression is functionally linked to any intracellular and/or extracellular
      factor(s) awaits further research.

PMID- 11287362
TI  - Adaptation of beta-cell mass to substrate oversupply: enhanced function with
      normal gene expression.
AB  - Although type 2 diabetes mellitus is associated with insulin resistance, many
      individuals compensate by increasing insulin secretion. Putative mechanisms
      underlying this compensation were assessed in the present study by use of 4-day
      glucose (GLC; 35% Glc, 2 ml/h) and lipid (LIH; 10% Intralipid + 20 U/ml heparin;
      2 ml/h) infusions to rats. Within 2 days of beginning the infusion of either
      lipid or glucose, plasma glucose profiles were normalized (relative to saline
      infused control rats; SAL; 0.45% 2 ml/h). During glucose infusion, plasma glucose
      was maintained in the normal range by an approximately twofold increase in plasma
      insulin and an approximately 80% increase in beta-cell mass. During LIH infusion,
      glucose profiles were also maintained in the normal range. Plasma insulin
      responses during feeding were doubled, and beta-cell mass increased 54%. For both
      groups, the increase in beta-cell mass was associated with increased beta-cell
      proliferation (98% increase during GLC and 125% increase during LIH). At the end
      of the 4-day infusions, no significant changes were observed in islet-specific
      gene transcription (i.e., the expression of islet hormone genes, glucose
      metabolism genes, and insulin transcription factors were unaffected). Two days
      after termination of the infusions, the glucose-stimulated plasma insulin
      response was increased approximately 67% in glucose-infused animals. No sustained
      effect on insulin secretory capacity was observed in the LIH animals. The
      increase in plasma insulin response after glucose infusion was achieved in the
      absence of any change in insulin clearance. We conclude that, in rats, an
      increase in insulin demand after an increase in glucose appearance or free fatty
      acid leads to an increase in beta-cell mass, mediated in part by an increase in
      beta-cell proliferation, and that these compensatory changes lead to increased
      insulin secretion, normal plasma glucose levels, and the maintenance of normal
      islet gene expression.

PMID- 11287363
TI  - High-fat hypocaloric diet modifies carbohydrate utilization of obese rats during
      weight loss.
AB  - The effects of fat content in the hypocaloric diet on whole body glucose
      oxidation and adipocyte glucose transport were investigated in two animal-feeding
      experiments. Diet-induced obese rats were food restricted to 75% of their
      previous energy intakes with either a high (45% by calorie) or a low (12% by
      calorie) corn oil diet for 9 wk (experiment 1) or 10 days (experiment 2). The
      losses of body weight (P < 0.05) and adipose depot weight (P < 0.05) were less in
      the 45% compared with the 12% fat group. During the dynamic phase of weight loss
      (day 10 of food restriction), plasma glucose and insulin concentrations were
      higher (P < 0.05) in the 45% than those in the 12% fat group. Whole body
      carbohydrate oxidation rate in response to an oral load of glucose was increased
      (P < 0.001) by food restriction in both dietary groups; however, carbohydrate
      oxidation rates were lower (P < 0.01) in the 45% than in the 12% fat-fed rats
      during the weight loss period. Adipocyte glucose transport was greater (P < 0.02)
      in the 45% than in the 12% fat group in an intra-abdominal adipose depot but not
      in subcutaneous fat. These data suggest that dietary fat content modifies whole
      body glucose oxidation and intra-abdominal adipocyte glucose uptake during weight
      loss.

PMID- 11287364
TI  - Cysteine regulates expression of cysteine dioxygenase and gamma-glutamylcysteine
      synthetase in cultured rat hepatocytes.
AB  - Rat hepatocytes cultured for 3 days in basal medium expressed low levels of
      cysteine dioxygenase (CDO) and high levels of gamma-glutamylcysteine synthetase
      (GCS). When the medium was supplemented with 2 mmol/l methionine or cysteine, CDO
      activity and CDO protein increased by >10-fold and CDO mRNA increased by 1.5- or
      3.2-fold. In contrast, GCS activity decreased to 51 or 29% of basal, GCS heavy
      subunit (GCS-HS) protein decreased to 89 or 58% of basal, and GCS mRNA decreased
      to 79 or 37% of basal for methionine or cysteine supplementation, respectively.
      Supplementation with cysteine consistently yielded responses of greater magnitude
      than did supplementation with an equimolar amount of methionine. Addition of
      propargylglycine to inhibit cystathionine gamma-lyase activity and, hence,
      cysteine formation from methionine prevented the effects of methionine, but not
      those of cysteine, on CDO and GCS expression. Addition of buthionine sulfoximine
      to inhibit GCS, and thus block glutathione synthesis from cysteine, did not alter
      the ability of methionine or cysteine to increase CDO. GSH concentration was not
      correlated with changes in either CDO or GCS-HS expression. The effectiveness of
      cysteine was equivalent to or greater than that of its precursors (S
      adenosylmethionine, cystathionine, homocysteine) or metabolites (taurine,
      sulfate). Taken together, these results suggest that cysteine itself is an
      important cellular signal for upregulation of CDO and downregulation of GCS.

PMID- 11287365
TI  - Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B
      activation in skeletal muscle.
AB  - To determine the molecular mechanism underlying hyperglycemia-induced insulin
      resistance in skeletal muscles, postreceptor insulin-signaling events were
      assessed in skeletal muscles of neonatally streptozotocin-treated diabetic rats.
      In isolated soleus muscle of the diabetic rats, insulin-stimulated 2-deoxyglucose
      uptake, glucose oxidation, and lactate release were all significantly decreased
      compared with normal rats. Similarly, insulin-induced phosphorylation and
      activation of Akt/protein kinase B (PKB) and GLUT-4 translocation were severely
      impaired. However, the upstream signal, including phosphorylation of the insulin
      receptor (IR) and insulin receptor substrate (IRS)-1 and -2 and activity of
      phosphatidylinositol (PI) 3-kinase associated with IRS-1/2, was enhanced. The
      amelioration of hyperglycemia by T-1095, a Na(+)-glucose transporter inhibitor,
      normalized the reduced insulin sensitivity in the soleus muscle and the impaired
      insulin-stimulated Akt/PKB phosphorylation and activity. In addition, the
      enhanced PI 3-kinase activation and phosphorylation of IR and IRS-1 and -2 were
      reduced to normal levels. These results suggest that sustained hyperglycemia
      impairs the insulin-signaling steps between PI 3-kinase and Akt/PKB, and that
      impaired Akt/PKB activity underlies hyperglycemia-induced insulin resistance in
      skeletal muscle.

PMID- 11287366
TI  - Auditory neglect and right parietal cortex.

PMID- 11287367
TI  - Semantic dementia: relevance to connectionist models of long-term memory.
AB  - Semantic dementia is a recently documented syndrome associated with non-Alzheimer
      degenerative pathology of the polar and inferolateral temporal neocortex, with
      relative sparing (at least in the early stages) of the hippocampal complex.
      Patients typically show a progressive deterioration in their semantic knowledge
      about people, objects, facts and the meanings of words. Yet, at least clinically,
      they seem to possess relatively preserved day-to-day (episodic) memory.
      Neuropsychological investigations of semantic dementia provide, therefore, a
      unique opportunity to investigate the organization of human long-term memory and,
      more specifically, to determine the relationship between semantic memory and
      other cognitive systems, such as episodic memory. In this review, we summarize
      recent empirical findings from patients with semantic dementia and discuss
      whether the neuropsychological phenomena of the disease are consistent with
      current cognitive and computational models of human long-term memory and amnesia.
      Six specific issues are addressed: (i) the relative preservation of category
      level (superordinate) compared with fine-graded (subordinate) semantic knowledge
      as the disease progresses; (ii) the better recall of recent autobiographical and
      semantic memories compared with those in the distant past; (iii) the preservation
      of new learning, as measured by recognition memory, early in the disease; (iv)
      the interaction between autobiographical experience and semantic knowledge in the
      current, but not the distant, time-period; (v) increased long-term forgetting of
      newly learned material; and (vi) impaired implicit memory. It is concluded that
      recent findings from semantic dementia offer strong support for the view that
      memory consolidation in humans is dependent upon interactions between the
      hippocampal complex and neocortex. Furthermore, these investigations have
      provided computational modellers of human memory with a novel set of
      neuropsychological data to be simulated and tested.

PMID- 11287368
TI  - Two types of auditory neglect.
AB  - Auditory neglect, defined as inattention to stimuli within the left hemispace, is
      mostly reported in association with left ear extinction in dichotic listening.
      However, it remains disputed as to how far dichotic extinction reflects a primary
      attentional deficit and is thus appropriate for the diagnosis of auditory
      neglect. We report here on four patients who presented left ear extinction in
      dichotic listening following right unilateral hemispheric lesions. Auditory
      spatial attention was assessed with two additional tasks: (i) diotic test by
      means of interaural time differences (ITDs), simulating bilateral simultaneous
      spatial presentation of the dichotic tasks without the inconvenience of
      interaural intensity or content difference; and (ii) sound localization. A
      hemispatial asymmetry on the ITD diotic test or a spatial bias on sound
      localization were found to be part of auditory neglect. Two patients (J.C.N. and
      M.B.) presented a marked hemispatial asymmetry favouring the ipsilesional
      hemispace in the ITD diotic test, but did not show any spatial bias in sound
      localization. Two other patients (A.J. and E.S.) had the reverse profile: no
      hemispatial asymmetry in the ITD diotic test, but a severe spatial bias directed
      to the ipsilesional side in sound localization. J.C.N. and M.B. had mainly
      subcortical lesions affecting the basal ganglia. A.J. and E.S. had cortical
      lesions in the prefrontal, superior temporal and inferior parietal areas. Thus,
      there are two behaviourally and anatomically distinct types of auditory neglect
      characterized by: (i) deficit in allocation of auditory spatial attention
      following lesions centred on basal ganglia; or (ii) distortion of auditory
      spatial representation following frontotemporoparietal lesions.

PMID- 11287369
TI  - Somatostatin- and neuropeptide Y-synthesizing neurones in the fascia dentata of
      humans with temporal lobe epilepsy.
AB  - We used in situ hybridization techniques to study the distribution of neurones
      synthesizing somatostatin mRNA and neuropeptide Y mRNA in the hilar region of the
      hippocampal formation of patients with temporal lobe epilepsy. In the dentate
      gyrus, somatostatin mRNA- and neuropeptide Y mRNA-synthesizing neurones were
      found to be exclusively located within the hilar region. Unlike animal models, no
      ectopic expression of either peptide was found in principal cells. The numbers of
      hilar interneurones expressing somatostatin mRNA and neuropeptide Y mRNA were
      compared with the degree of hilar cell loss determined by immunohistochemistry
      against neuronal nuclear antigen. The numbers of somatostatin and neuropeptide Y
      mRNA-synthesizing neurones varied considerably between patients, but both were
      found to be highly correlated to the total number of neuronal nuclear antigen
      immunoreactive hilar neurones. These results suggest that loss of somatostatin
      and neuropeptide Y interneurones occurs in proportion to overall hilar cell loss,
      and therefore the hypothesis of a selective loss of these interneurones in
      temporal lobe epilepsy seems unlikely.

PMID- 11287370
TI  - Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in
      exon skipping.
AB  - Nonsense mutations outside the splicing consensus sequence have been reported to
      cause skipping of the nonsense-containing exon in several human diseases. We
      describe, for the first time, nonsense-mediated exon skipping in the laminin
      alpha2 (LAMA2) gene. Two siblings from a consanguineous family had altered
      expression of the laminin alpha2 chain and moderate clinical manifestations. In
      both we identified the new nonsense mutation Arg744Stop, which we expected to
      result in a totally non-functional polypeptide. However, analysis of the
      transcript revealed skipping of exon 15, containing the mutation, even though the
      consensus sequences for splicing at both ends of the exon and the beginning of
      intron 15 were unaltered. Exon skipping restored the open reading frame of the
      mutant transcript and resulted in a truncated protein. In cases where the genetic
      findings do not elucidate the phenotype, mRNA analysis is necessary to clarify
      the primary effect of mutations. Our findings also point to the necessity of
      immunochemical screening for expression of laminin alpha2 chain in atypical
      dystrophic adults as well as children.

PMID- 11287372
TI  - A study of tremor in multiple sclerosis.
AB  - One hundred patients with definite multiple sclerosis, who were randomly selected
      from a multiple sclerosis unit in London, were examined in order to study the
      prevalence, subtypes, clinical features and associated disability of tremor in
      this population. There were 35 males and 65 females with an average age of 47
      years and an average disease duration of 18.8 years. The mean tremor duration was
      13 years, with a median latency of 11 years from disease onset to appearance of
      tremor. Tremor was reported in 37 patients but was detected in 58. Tremor
      affected the arms (56%), legs (10%), head (9%) and trunk (7%). There were no
      examples of face, tongue or jaw tremor. All the patients had action tremor,
      either postural or kinetic (including intention). Rest, Holmes' ('rubral') and
      primary orthostatic tremors were not encountered. Tremor severity ranged from
      minimal in 27%, to mild in 16% and moderate or severe in 15% of cases. Tremor
      severity correlated with the degree of dysarthria, dysmetria and
      dysdiadochokinesia but not with grip strength. In order to determine the clinical
      characteristics of these tremors, the action tremors of the upper limbs were
      subclassified according to the predominant site and state of tremulous activity.
      Of the 50 patients with tremor in the right arm, 32% had distal postural tremor,
      36% had distal postural and kinetic tremor, 16% had proximal postural and kinetic
      tremor; 4% had proximal and distal postural and kinetic tremor and 12% isolated
      intention tremor. Twenty-seven percent of the overall study population had tremor
      related disability and 10% had incapacitating tremor. Patients with abnormal
      tremor (severity grade >1/10) were more likely than those without tremor to be
      wheelchair dependent and have a worse Expanded Disability Systems Score, but
      Barthel activities of daily living indices and cognitive scores were comparable
      in the two groups.

PMID- 11287371
TI  - Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP
      induced interleukin-4 and interferon-gamma response in blood cells.
AB  - Copolymer-1 (Copaxone or COP) inhibits experimental allergic encephalomyelitis
      and has beneficial effects in multiple sclerosis. There is presently no practical
      in vitro assay for monitoring the immunological effects of COP. We used an
      automated, computer-assisted enzyme-linked immunoadsorbent spot assay for
      detecting COP-induced interferon-gamma (IFN-gamma)- and interleukin-4 (IL-4)
      producing cells and a standard proliferation assay to assess the immunological
      response to COP in peripheral blood mononuclear cells from 20 healthy donors, 20
      untreated multiple sclerosis patients and 20 COP-treated multiple sclerosis
      patients. Compared with untreated and healthy controls, COP-treated patients
      showed (i) a significant reduction of COP-induced proliferation; (ii) a positive
      IL-4 Elispot response mediated predominantly by CD4 cells after stimulation with
      a wide range of COP concentrations; and (iii) an elevated IFN-gamma response
      partially mediated by CD8 cells after stimulation with high COP concentrations.
      All three effects were COP-specific as they were not observed with the control
      antigens, tuberculin-purified protein or tetanus toxoid. The COP-induced changes
      were consistent over time and allowed correct identification of COP-treated and
      untreated donors in most cases. We propose that these criteria may be helpful to
      monitor the immunological response to COP in future clinical trials.

PMID- 11287373
TI  - A double dissociation between accuracy and time of execution on attentional tasks
      in Alzheimer's disease and multi-infarct dementia.
AB  - Two cancellation/attentional tasks: (i) Lines Cancellation (LC) and Multiple
      Features Targets Cancellation (MFTC) and (ii) a standard battery of
      neuropsychological tests, the Mental Deterioration Battery (MDB), were
      administered to 68 patients with dementia of the Alzheimer's type (DAT) and 40
      patients with multi-infarct dementia (MID), who were accurately matched for the
      overall severity of dementia, and to 40 normal controls. Both accuracy and time
      of execution were considered in evaluating performance on the two cancellation
      tasks, which involved visuospatial exploration and psychomotor speed, but were
      differently demanding in terms of selective attention. On the first cancellation
      task (LC), requiring a lower attentional load, the two demented patient groups
      performed at the same level of accuracy. On the second cancellation task (MFTC),
      which was more demanding in terms of selective and divided attention, DAT
      patients were significantly less accurate than MID patients, making a higher
      number of 'false-alarm' errors. Conversely, the time employed in the execution of
      both LC and MFTC took longer for MID than for DAT patients, suggesting a greater
      impairment of psychomotor speed in MID. In the MDB, DAT patients scored
      significantly worse than MID patients on several measures of episodic memory (the
      immediate recall, delayed recall and delayed recognition of Rey's Auditory Verbal
      Learning Test) and on a test of visual-spatial memory. These data suggest that,
      while psychomotor speed and the lower (sensorimotor) levels of attention are
      preferentially impaired in subcortical forms of dementia such as MID, the higher
      levels of selective and divided attention are more markedly disrupted in the
      Alzheimer type of dementia.

PMID- 11287374
TI  - Altered brain functional connectivity and impaired short-term memory in
      Alzheimer's disease.
AB  - To examine functional interactions between prefrontal and medial temporal brain
      areas during face memory, blood flow was measured in patients with Alzheimer's
      disease and healthy controls using PET. We hypothesized that controls would show
      correlated activity between frontal and posterior brain areas, including the
      medial temporal cortex, whereas patients would not, although frontal activity per
      se might be spared or even increased compared with controls. We used a delayed
      match to sample paradigm with delays from 1 to 16 s. There was no change in
      recognition accuracy with increasing delay in controls, whereas patients showed
      impaired recognition over all delays that worsened as delay increased. Controls
      showed increased activity in the bilateral prefrontal and parietal cortex with
      increasing delay, whereas the patients had increased activity in the right
      prefrontal, anterior cingulate and left amygdala. Increased activity in the right
      prefrontal cortex was associated with better memory performance in both groups
      and activity in the left amygdala was correlated with better performance in the
      patients. Based on these task and behavioural effects, we examined functional
      connectivity of the right prefrontal cortex and left amygdala in both groups by
      determining those areas whose activity was correlated with activity in these
      regions. In controls, activity in the right prefrontal cortex was positively
      correlated with blood flow in the left prefrontal cortex, bilateral extrastriate
      and parietal areas and the right hippocampus. In patients, activity in the right
      prefrontal cortex was correlated mainly with other prefrontal regions. Areas
      where activity was correlated with the left amygdala in patients included the
      bilateral posterior parahippocampal gyri, a number of left prefrontal regions,
      anterior and posterior cingulate, thalamus, and insula. Controls had a relatively
      restricted set of regions where activity correlated with the left amygdala,
      mainly temporal and occipital areas. These results support the idea of a
      functional disconnection between the prefrontal cortex and the hippocampus in
      Alzheimer's disease and suggest that memory breakdown in early Alzheimer's
      disease is related to a reduction in the integrated activity within a distributed
      network that includes these two areas. The unexpected finding of increased
      involvement of the amygdala suggests that the patients may have processed the
      emotional content of the faces to a greater degree than did the controls.
      Furthermore, the positive association between amygdala activity and memory
      performance in the patients suggests a possible compensatory role for an emotion
      related network of regions.

PMID- 11287375
TI  - Functional changes of the primary somatosensory cortex in patients with
      unilateral cerebellar lesions.
AB  - Although cerebellar lesions do not cause evident sensory deficits, it has been
      suggested recently that the cerebellum might play a role in sensory acquisition
      and discrimination. To determine whether the cerebellum influences the early
      phases of cortical somatosensory processing, we recorded cortical somatosensory
      evoked potentials after median nerve stimulation in five patients with unilateral
      cerebellar damage. We also performed a dipolar source analysis of traces by means
      of brain electrical source analysis. In all patients, the amplitude of the
      frontal N24 and parietal P24 components, as well as the strength of the
      corresponding dipolar sources, were significantly smaller after stimulation of
      the symptomatic side. These neurophysiological findings indicate that the primary
      somatosensory cortical processing is altered after contralateral cerebellar
      damage. They represent the first indication of a possible substrate for the
      reduction in cerebral blood flow observed in the parietal cortex after cerebellar
      lesion. Furthermore, the present data allow characterization of the functional
      influence of the cerebellar input to the primary somatosensory cortex as
      specifically acting over the inhibitory components of somatosensory processing.

PMID- 11287376
TI  - Prospective study of selective peripheral denervation for botulinum-toxin
      resistant patients with cervical dystonia.
AB  - We have carried out a prospective study of selective peripheral denervation (SPD)
      in cervical dystonia (CD) patients with primary or secondary botulinum toxin (BT)
      treatment failure using independent standardized assessment. Patients referred
      for surgery had a standardized clinical examination, neck muscle EMG,
      videofluoroscopic swallow and CT of the cervical spine, and were selected for
      surgery on the basis of the results of these investigations. CD severity,
      disability and pain were assessed preoperatively and at 3, 6, 9, 12 and 18 months
      postoperatively using the Toronto Western Spasmodic Torticollis Rating Scale
      (TWSTRS). Severity of head tremor and dysphagia were scored using established
      rating scales. Additionally, psychosocial function was assessed in a
      representative subsample of patients (n = 12) using several established
      questionnaires. Of the 62 patients who were assessed, 22 (35.5%) were not offered
      surgery, most commonly because of widespread dystonia. Of the remaining 40
      patients, 37 have so far had surgery, 31 of whom have been followed up for at
      least 1 year, and 15 for 18 months after surgery (mean follow-up duration 16.7
      months). Using the TWSTRS global outcome score, 68% of patients derived
      functionally relevant improvement at 12 months after surgery. In the entire
      operated group, total TWSTRS scores were reduced by 30% at 6 and 12 months after
      surgery (P < 0.0001). The subscores for severity, disability and pain were
      reduced by 20, 30 and 40%, respectively, at 6 months (P < or = 0.01) and 20, 40
      and 30%, respectively, at 12 months (P < 0.01). Pain increased over time, which
      appeared to result from muscle reinnervation. TWSTRS scores were not
      significantly improved in the six patients with primary BT treatment failure.
      Head tremor did not change. There was a significant improvement of body concept,
      perceived disfigurement, stigma, and quality of life in the 12 patients whose
      psychosocial function was assessed. Preoperative disability and restriction of
      head movement were negatively correlated and the initial response to BT treatment
      positively correlated with global outcome score. Spread or deterioration of
      dystonia elsewhere in the body occurred in three patients, with unpleasant
      sensory symptoms in denervated posterior cervical segments occurring in 14. Ten
      patients developed mild to moderate dysphagia, and two developed severe
      dysphagia. We conclude that SPD is an effective treatment for patients with
      secondary, but probably not for those with primary, BT treatment failure.
      Reinnervation is not infrequent and can compromise outcome. Postoperative
      morbidity is low, but there is a risk of dysphagia.

PMID- 11287377
TI  - Changes in dopamine availability in the nigrostriatal and mesocortical
      dopaminergic systems by gait in Parkinson's disease.
AB  - The basal ganglia play a role in controlling movement during gait. The aim of the
      present study was to investigate changes in dopamine transporter (DAT)
      availability in the striatum and extrastriatal region in association with walking
      exercise in six normal subjects and seven age-matched unmedicated patients with
      Parkinson's disease. This was done by comparing DAT radioligand uptake in the
      dopaminergic projection areas after gait with that under the resting condition
      using a DAT probe, 11C-labelled 2-beta-carbomethoxy-3beta-(4-fluorophenyl)
      tropane ([11C]CFT) and PET. Physiological parameters were stable during and after
      gait in both groups. The regions of interest method for measuring differences in
      [11C]CFT uptake level and voxel-based statistical parametric mapping (SPM96)
      showed that [11C]CFT uptake in the striatum (specifically the putamen) was
      decreased by gait to a greater extent in normal subjects, whereas a significant
      reduction in [11C]CFT uptake was not found in the putamen but in the caudate and
      orbitofrontal cortex in Parkinson's disease patients. These results are the first
      in vivo evidence that DAT availability is reduced in the nigrostriatal projection
      area by basic human behaviour, i.e. gait. Alterations in this availability in
      Parkinson's disease suggested that shifted activation in the medial striatum and
      the mesocortical dopaminergic system might reflect the pathophysiology of
      parkinsonian gait.

PMID- 11287378
TI  - The crossing of the spinothalamic tract.
AB  - The question whether the spinothalamic and spinoreticular fibres cross the cord
      transversely or diagonally was investigated in cases of anterolateral cordotomy
      and in a case of thrombosis of the anterior spinal artery. The pattern of sensory
      loss following transection of the anterolateral quadrant of the cord consists of
      a narrow area of decreased nociception and thermanalgesia at the level of the
      incision; it extends for 1-2 segments cranial and cordal to the incision. This
      area is immediately cranial to the area of total loss of these modalities. This
      pattern of sensory loss is explained as follows. The cordotomy incision transects
      two groups of fibres: those that are already within the anterior and
      anterolateral funiculi and those that are crossing the cord. The area of total
      thermanaesthesia and analgesia is due to transection of fibres that are already
      within this region. The area of partial sensory loss is due to transection of the
      fibres that are crossing the cord at that level. Owing to the craniocaudal extent
      of the branches of the dorsal roots, there is an overlap of their collaterals
      that results in every spinothalamic neurone receiving an input from several
      dorsal roots. The narrow cordotomy incision thus divides the few fibres crossing
      at that level, causing diminished noxious and thermal sensibility over a few
      segments above and below the incision. These facts can be accounted for only on
      the assumption that these spinothalamic fibres are crossing the cord
      transversely. This evidence of transverse crossing was found in the cervical,
      thoracic and lumbar segments. There were three of 63 cordotomies for which this
      explanation of the partial sensory loss could not be maintained. Although no
      explanation has been suggested, this is unlikely to be due to the fibres crossing
      the cord diagonally.

PMID- 11287379
TI  - The neural correlates of person familiarity. A functional magnetic resonance
      imaging study with clinical implications.
AB  - Neural activity was measured in 10 healthy volunteers by functional MRI while
      they viewed familiar and unfamiliar faces and listened to familiar and unfamiliar
      voices. The familiar faces and voices were those of people personally known to
      the subjects; they were not people who are more widely famous in the media.
      Changes in neural activity associated with stimulus modality irrespective of
      familiarity were observed in modules previously demonstrated to be activated by
      faces (fusiform gyrus bilaterally) and voices (superior temporal gyrus
      bilaterally). Irrespective of stimulus modality, familiarity of faces and voices
      (relative to unfamiliar faces and voices) was associated with increased neural
      activity in the posterior cingulate cortex, including the retrosplenial cortex.
      Our results suggest that recognizing a person involves information flow from
      modality-specific modules in the temporal cortex to the retrosplenial cortex. The
      latter area has recently been implicated in episodic memory and emotional
      salience, and now seems to be a key area involved in assessing the familiarity of
      a person. We propose that disturbances in the information flow described may
      underlie neurological and psychiatric disorders of the recognition of familiar
      faces, voices and persons (prosopagnosia, phonagnosia and Capgras delusion,
      respectively).

PMID- 11287380
TI  - Effects of temperature on the excitability properties of human motor axons.
AB  - The effects of temperature on parameters of motor nerve excitability were
      investigated in 10 healthy human subjects. The median nerve was stimulated at the
      wrist and compound muscle action potentials were recorded from the abductor
      pollicis brevis. Multiple excitability measures were recorded: stimulus-response
      curves, the strength-duration time constant (tauSD), threshold electrotonus, a
      current-threshold relationship and the recovery of excitability following
      supramaximal activation. Recordings were made at wrist temperatures of 35, 32 and
      29 degrees C by immersing the arm proximal to the wrist in a water-bath. Cooling
      increased the relative refractory period by 7.8% per degree C (P < 0.0001),
      slowed the accommodation to depolarizing currents by 4.0% per degree C (P <
      0.0001) and increased tauSD by 2.6% per degree C (P < 0.01), but most other
      excitability parameters were not affected significantly. The effects of
      temperature on threshold electrotonus were investigated further in separate
      studies on two subjects over the range 28-36 degrees C and found to be complex.
      Whereas the rate of accommodation to depolarizing current was closely related to
      instantaneous temperature, the threshold increase induced by hyperpolarizing
      current was most sensitive to changes in temperature, probably because warming
      the nerve causes a transient hyperpolarization by accelerating the electrogenic
      sodium pump. Consequently, it may be preferable to make allowances for
      differences in skin temperature when testing patients for abnormal excitability
      parameters, rather than to change the temperature to a standard value. For most
      excitability parameters, however, temperature control is not as important as it
      is for conduction velocity measurements.

PMID- 11287381
TI  - Modulation of presynaptic inhibition and disynaptic reciprocal Ia inhibition
      during voluntary movement in spasticity.
AB  - The aim of the study was to investigate whether impaired control of transmission
      in spinal inhibitory pathways contributes to the functional disability of
      patients with spasticity. To this end, transmission in the pathways mediating
      disynaptic reciprocal Ia inhibition and presynaptic inhibition was investigated
      in 23 healthy subjects and 20 patients with spastic multiple sclerosis during
      ankle dorsiflexion and plantar flexion. In healthy subjects, but not in spastic
      patients, the soleus H reflex was depressed at the onset of dorsiflexion (300 ms
      rise time, 20% of maximal voluntary effort). At the onset of plantar flexion, the
      soleus H reflex was more facilitated in the healthy subjects than in the
      patients. The H reflex increased more with increasing level of tonic plantar
      flexion and decreased more with dorsiflexion in the healthy subjects than in the
      spastic patients. Transmission in the disynaptic Ia reciprocal inhibitory pathway
      from ankle dorsiflexors to plantar flexors was investigated by conditioning the
      soleus H reflex by previous stimulation of the common peroneal nerve
      (conditioning-test interval 2-3 ms; stimulation intensity 1.05 times the motor
      response threshold). At the onset of dorsiflexion, stimulation of the common
      peroneal nerve evoked a significantly larger inhibition than at rest in the
      healthy subjects but not in the spastic patients. At the onset of plantar flexion
      the inhibition decreased in the healthy subjects, but because only weak
      inhibition was observed at rest in the patients it was not possible to determine
      whether a similar decrease occurred in this group. There were no differences in
      the modulation of inhibition during tonic plantar flexion and dorsiflexion in the
      two populations. Presynaptic inhibition of Ia afferents terminating on soleus
      motor neurones was evaluated from the monosynaptic Ia facilitation of the soleus
      H reflex evoked by femoral nerve stimulation. Femoral nerve facilitation was
      decreased at the onset of dorsiflexion and increased at the onset of plantar
      flexion in the healthy subjects and patients, but the changes were significantly
      greater in the healthy subjects. There was no difference between the two
      populations in the modulation of presynaptic inhibition during tonic plantar
      flexion and dorsiflexion. It is suggested that the abnormal regulation of
      disynaptic reciprocal inhibition and presynaptic inhibition in patients with
      spasticity is responsible for the abnormal modulation of stretch reflexes in
      relation to voluntary movement in these patients. Lack of an increase in
      reciprocal inhibition and presynaptic inhibition at the onset of dorsiflexion may
      be responsible for the tendency to elicitation of unwanted stretch reflex
      activity and co-contraction of antagonistic muscles in patients with spasticity.

PMID- 11287382
TI  - Responses of the ant Lasius niger to various compounds perceived as sweet in
      humans: a structure-activity relationship study.
AB  - A behavioural study on the ant Lasius niger was performed by observing its
      feeding responses to 85 compounds presented in a two-choice situation (tested
      compound versus water control or sucrose solution). Among these compounds, only
      21 were phagostimulating: six monosaccharides (D-glucose, 6-deoxy-D-glucose, L
      galactose, L-fucose, D-fructose, L-sorbose), four derivatives of D-glucose
      (methyl alpha-D-glucoside, D-gluconolactone and 6-chloro- and 6-fluoro-deoxy-D
      glucose), five disaccharides (sucrose, maltose, palatinose, turanose and
      isomaltose), one polyol glycoside (maltitol), three trisaccharides (melezitose,
      raffinose and maltotriose) and two polyols (sorbitol and L-iditol). None of the
      16 non-carbohydrate non-polyol compounds tested, although perceived as sweet in
      humans, was found to be active in ants. The molar order of effectiveness of the
      major naturally occuring compounds (melezitose > sucrose = raffinose > D-glucose
      > D-fructose = maltose = sorbitol) is basically different from the molar order of
      their sweetness potency in humans (sucrose > D-fructose > melezitose > maltose >
      D-glucose = raffinose = sorbitol). On a molar basis melezitose is in L. niger
      about twice as effective as sucrose or raffinose, while D-glucose and D-fructose
      are three and four times less effective, respectively, than sucrose or raffinose.
      From a structure-activity relationship study it was inferred that the active
      monosaccharides and polyols should interact with the ant receptor through only
      one type of receptor, through the same binding pocket and the same binding
      residues, via a six-point interaction. The high effectiveness of melezitose in L.
      niger mirrors the feeding habits of these ants, which attend homopterans and are
      heavy feeders on their honeydew, which is very rich in this carbohydrate.

PMID- 11287383
TI  - The influence of essential oils on human attention. I: alertness.
AB  - Scientific research on the effects of essential oils on human behavior lags
      behind the promises made by popular aromatherapy. Nearly all aspects of human
      behavior are closely linked to processes of attention, the basic level being that
      of alertness, which ranges from sleep to wakefulness. In our study we measured
      the influence of essential oils and components of essential oils [peppermint,
      jasmine, ylang-ylang, 1,8-cineole (in two different dosages) and menthol] on this
      core attentional function, which can be experimentally defined as speed of
      information processing. Substances were administered by inhalation; levels of
      alertness were assessed by measuring motor and reaction times in a reaction time
      paradigm. The performances of the six experimental groups receiving substances (n
      = 20 in four groups, n = 30 in two groups) were compared with those of
      corresponding control groups receiving water. Between-group analysis, i.e.
      comparisons between experimental groups and their respective control groups,
      mainly did not reach statistical significance. However, within-group analysis
      showed complex correlations between subjective evaluations of substances and
      objective performance, indicating that effects of essentials oils or their
      components on basic forms of attentional behavior are mainly psychological.

PMID- 11287384
TI  - Judgement of odor intensity is influenced by subjects' knowledge of the odor
      source.
AB  - Odor perception, including intensity, is affected by knowledge of odor source.
      For 76 subjects tested with 24 everyday odorants, ratings of intensity,
      pleasantness and familiarity were enhanced when subjects either could identify
      the odor source themselves or were provided with the name by the experimenter.
      Ratings were highest when subjects judged that the names provided matched their
      own perception, suggesting an interaction between individuals' cognitive
      representation of odors and their immediate perceptual experience.

PMID- 11287385
TI  - NaCl detection thresholds: comparison of Fischer 344 and Wistar rats.
AB  - Adult Fischer 344 (F344) rats fail to display any preference for NaCl solutions
      at concentrations typically preferred by other rat strains. To determine whether
      this behavior is due to a strain difference in NaCl detection threshold, a
      conditioned taste aversion (CTA) was first established to a suprathreshold
      concentration of NaCl (0.1 M). Then, a series of dilute NaCl solutions, ranging
      from 0.0 to 0.011 M NaCl, were presented to F344 (n = 16) and Wistar (n = 16)
      rats. The lowest concentration at which there was a reliable difference in the
      preference scores of conditioned and control rats was defined as the detection
      threshold. Results indicate that the detection threshold for NaCl lies between
      0.001 and 0.002 M NaCl for both F344 and Wistar rats. The addition of the sodium
      channel blocker amiloride to the NaCl solutions raised the detection threshold 10
      fold to 0.03-0.04 M NaCl for both strains of rats. These results suggest that the
      NaCl detection thresholds of F344 and Wistar rats are similar and that these
      strains do not differ in the degree to which amiloride raises this threshold.

PMID- 11287386
TI  - IP(3) receptor type 3 and PLCbeta2 are co-expressed with taste receptors T1R and
      T2R in rat taste bud cells.
AB  - The Ca(2+) signaling cascade has been reported to be activated by many tastants
      in vertebrate taste systems. Recently we have shown that G(i2) and phospholipase
      Cbeta2 (PLCbeta2) are co-expressed in a subset of taste bud cells and are
      possibly involved in Ca(2+) triggering of taste signaling in rats. We report here
      that, as a component downstream of PLCbeta2, the type 3 isoform of the inositol
      1,4,5-trisphosphate (IP(3)) receptor (IP(3)R3) is specifically expressed in the
      same cells as PLCbeta2 in rat taste buds. We also show that cells expressing
      rT2R9, a probable cycloheximide receptor, are included among PLCbeta2- and
      IP(3)R3-positive cells, as in the case of rT1R2, a different type of taste
      receptor. Our findings indicate that PLCbeta2 and IP(3)R3 co-localize together
      with G(i2) as downstream components of two different types of taste receptors,
      T1R and T2R, in taste bud cells.

PMID- 11287387
TI  - Implicit learning and implicit memory for odors: the influence of odor
      identification and retention time.
AB  - One hundred and fifty-two subjects, divided into eight groups, were exposed to a
      room with a low concentration of either orange or lavender and to an odorless
      room. In a careful double-blind procedure, neither the subjects nor the
      experimenters were made aware of the presence of the odors in the experimental
      conditions. Later they were asked to indicate how well each of 12 odor stimuli,
      including the experimental and control odors, befitted each of 12 visual
      contexts, including the exposure rooms. At the end of this session they rated the
      pleasantness and the familiarity of the odors, and identified them by name.
      Finally they were debriefed and asked specifically whether they had perceived the
      experimental odors anywhere in the building. The results of four subjects who
      answered positively to the latter question were omitted. The results confirm the
      earlier finding that non-identifiers implicitly link odor and exposure room,
      whereas identifiers do not show such a link. It is suggested that episodic
      information is an essential constituent of olfactory memory and that its function
      is comparable to that of form and structure in visual and auditory memory
      systems.

PMID- 11287388
TI  - Effects of chiral fragrances on human autonomic nervous system parameters and
      self-evaluation.
AB  - The effects of chiral fragrances (enantiomers of limonene and carvone) on the
      human autonomic nervous system (ANS) and on self-evaluation were studied in 20
      healthy volunteers. Each fragrance was administered to each subject by inhalation
      using an A-A-B design. Individuals were tested in four separate sessions; in one
      session one fragrance was administered. ANS parameters recorded were skin
      temperature, skin conductance, breathing rate, pulse rate, blood oxygen
      saturation and systolic as well as diastolic blood pressure. Subjective
      experience was assessed in terms of mood, calmness and alertness on visual analog
      scales. In addition, fragrances were rated in terms of pleasantness, intensity
      and stimulating property. Inhalation of (+)-limonene led to increased systolic
      blood pressure, subjective alertness and restlessness. Inhalation of (-)-limonene
      caused an increase in systolic blood pressure but had no effects on psychological
      parameters. Inhalation of (-)-carvone caused increases in pulse rate, diastolic
      blood pressure and subjective restlessness. After inhalation of (+)-carvone
      increased levels of systolic as well as diastolic blood pressure were observed.
      Correlational analyses revealed that changes in both ANS parameters and self
      evaluation were in part related to subjective evaluation of the odor and suggest
      that both pharmacological and psychological mechanisms are involved in the
      observed effects. In conclusion, the present study indicates that: (i) prolonged
      inhalation of fragrances influences ANS parameters as well as mental and
      emotional conditions; (ii) effects of fragrances are in part based on subjective
      evaluation of odor; (iii) chirality of odor molecules seems to be a central
      factor with respect to the biological activity of fragrances.

PMID- 11287391
TI  - An environmental nuisance: odor concentrated and transported by dust.
AB  - Intensive swine production generates odorous emissions which flow from the
      buildings housing the animals. High ventilation rates bring in fresh air, remove
      heat and moisture and enhance pork productivity. Numerous compounds contribute to
      the uniquely offensive odors from swine facilities, including fatty acids,
      amines, aromatics and sulfur compounds. Dust particles, which originate
      predominantly from feces and feed, can adsorb and concentrate odorants in swine
      facilities. In addition, organic particles can decay and generate odorous
      compounds. Odorants can exist in much higher concentrations in the dust particles
      than in equivalent volumes of air. Thus, inhalation of odorous dust and
      deposition of the dust particles in the mucus overlying the olfactory mucosa are
      likely responsible for some odor-related complaints by swine farm neighbors.
      Accurate prediction of odor transport and dispersion downwind from swine farms
      may require models of dust dispersion and correlation between dust and odorant
      levels. Unfortunately, many approaches to estimating odor impact currently
      incorporate filtering of air to remove particulate matter before sensing by
      humans or electronic sensors. Accelerated progress in understanding this and
      other 'real world' odor control problems will require methodological innovations
      that allow quantification of odor in response to air streams containing vapor and
      particulate phases.

PMID- 11287392
TI  - Candidate physiological measures of annoyance from airborne chemicals.
AB  - Annoyance due to short-term exposure to airborne chemicals is a key factor in
      modern environmental research. Unpleasant odors or those that are believed
      harmful can annoy us. Since annoyance is modulated by the psychological and
      physiological states of the exposed persons, it is essential that we understand
      how these factors interact with environmental stimuli to yield a given level of
      this response. A potentially fruitful approach in this effort may be to treat
      annoyance as an emotion induced by the odor, and possibly irritation, resulting
      from chemical exposures. In this way, methods applied to assess induced emotions
      will likely be of value in elucidating annoyance. A rationale is presented for
      use of the startle reflex to elucidate the motor component of annoyance, which is
      manifest as a redirecting of attention towards the annoying odor (or irritant).
      Although evidence supporting the use of breathing changes to assess the
      vegetative component of annoyance is somewhat more scattered and indirect, this
      approach seems likely to be the most fruitful for future research. Experiments to
      enhance our understanding of annoyance using these two non-verbal end-points are
      outlined.

PMID- 11287393
TI  - Odor-associated health complaints: competing explanatory models.
AB  - Physical symptoms may be reported in workplace and community settings in which
      odorous airborne chemicals are present. Despite the relative frequency of such
      reports, clinicians, public health authorities and sensory scientists often
      experience difficulty interpreting odor-associated symptoms. The approach to
      interpretation advocated in this review involves: (i) understanding the
      toxicology of the agent(s) involved (in particular their relative irritant and
      odorant potencies); (ii) assessing exposure parameters (i.e. concentration and
      duration). Depending upon exposure concentration, duration and relative irritant
      and odorant potencies, a variety of pathophysiological mechanisms may be invoked
      in explaining odor-associated health symptoms. Some of these imputed mechanisms
      fall under the traditional scope of toxicology and others involve attitudinal
      and/or behavioral responses to odors.

PMID- 11287394
TI  - Measurements of the effects of air quality on sensory perception.
AB  - Occupants in indoor non-industrial environments decide whether the indoor air
      quality is acceptable or not. This paper describes the method by which the
      assessments of acceptability of air quality can be used to measure short-term
      sensory effects on humans caused by indoor exposures. Advantages and
      disadvantages of the method are discussed in the light of a need for future
      research in order to fully understand how many variables (environmental,
      organismic, physiological and psychological) influence the ratings of
      acceptability of air quality and to learn how the results obtained in laboratory
      experiments can be used to predict responses in natural environments.

PMID- 11287395
TI  - Glycans as legislators of host-microbial interactions: spanning the spectrum from
      symbiosis to pathogenicity.
AB  - The number of microbes associated with our gut likely exceeds our total number of
      somatic and germ cells. Despite their numbers, almost nothing is known about the
      molecular mechanisms that determine whether the interaction between a microbial
      species and its host will be beneficial. Recent results obtained from in vivo
      models have revealed critical roles for glycoconjugates in helping define the
      outcome of two such host-microbial relationships. In one case, attachment of
      Helicobacter pylori to fucosylated or sialylated glycans produced by various
      gastric epithelial lineages and their progenitors skews the destiny of
      colonization toward pathogenicity. In the second case, a molecular dissection of
      how Bacteroides thetaiotaomicron, a normal inhabitant of the distal small
      intestine, is able to communicate with intestinal epithelial cells has revealed a
      novel role for host fucosylated glycans in forging a mutually beneficial
      relationship. These observations lend support to the hypothesis that the capacity
      to synthesize diverse carbohydrate structures may have arisen in part from our
      need to both evade pathogenic relationships and to coevolve symbiotic
      relationships with our nonpathogenic resident microbes.

PMID- 11287396
TI  - Biochemical engineering of the N-acyl side chain of sialic acid: biological
      implications.
AB  - N-Acetylneuraminic acid is the most prominent sialic acid in eukaryotes. The
      structural diversity of sialic acid is exploited by viruses, bacteria, and toxins
      and by the sialoglycoproteins and sialoglycolipids involved in cell-cell
      recognition in their highly specific recognition and binding to cellular
      receptors. The physiological precursor of all sialic acids is N-acetyl D
      mannosamine (ManNAc). By recent findings it could be shown that synthetic N-acyl
      modified D-mannosamines can be taken up by cells and efficiently metabolized to
      the respective N-acyl-modified neuraminic acids in vitro and in vivo.
      Successfully employed D-mannosamines with modified N-acyl side chains include N
      propanoyl- (ManNProp), N-butanoyl- (ManNBut)-, N-pentanoyl- (ManNPent), N
      hexanoyl- (ManNHex), N-crotonoyl- (ManNCrot), N-levulinoyl- (ManNLev), N-glycolyl
      (ManNGc), and N-azidoacetyl D-mannosamine (ManNAc-azido). All of these compounds
      are metabolized by the promiscuous sialic acid biosynthetic pathway and are
      incorporated into cell surface sialoglycoconjugates replacing in a cell type
      specific manner 10-85% of normal sialic acids. Application of these compounds to
      different biological systems has revealed important and unexpected functions of
      the N-acyl side chain of sialic acids, including its crucial role for the
      interaction of different viruses with their sialylated host cell receptors. Also,
      treatment with ManNProp, which contains only one additional methylene group
      compared to the physiological precursor ManNAc, induced proliferation of
      astrocytes, microglia, and peripheral T-lymphocytes. Unique, chemically reactive
      ketone and azido groups can be introduced biosynthetically into cell surface
      sialoglycans using N-acyl-modified sialic acid precursors, a process offering a
      variety of applications including the generation of artificial cellular receptors
      for viral gene delivery. This group of novel sialic acid precursors enabled
      studies on sialic acid modifications on the surface of living cells and has
      improved our understanding of carbohydrate receptors in their native environment.
      The biochemical engineering of the side chain of sialic acid offers new tools to
      study its biological relevance and to exploit it as a tag for therapeutic and
      diagnostic applications.

PMID- 11287397
TI  - Characterization of monoclonal antibody MEST-2 specific to glucosylceramide of
      fungi and plants.
AB  - An IgG2a monoclonal antibody anti-glucosylceramide was established and termed
      MEST-2. High performance thin layer chromatography immunostaining, and solid
      phase radioimmunoassay showed that MEST-2 reacts with glucosylceramide from yeast
      and mycelium forms of Paracoccidioides brasiliensis, Histoplasma capsulatum, and
      Sporothrix schenckii; from hyphae of Aspergillus fumigatus; and from yeast forms
      of Candida albicans, Cryptococcus neoformans, Cryptococcus laurentii, and
      Cryptococcus albidus. Studies on the fine specificity of MEST-2 showed that it
      recognizes the beta-D-glucose residue, and that the 2-hydroxy group present in
      the fatty acid is an important auxiliary feature for the antibody binding. It was
      also demonstrated that phosphatidylcholine and ergosterol modulate MEST-2
      reactivity to glucosylceramide, by solid-phase radioimmunoassay. Indirect
      immunofluorescence showed that MEST-2 reacts with the surface of yeast forms of
      P. brasiliensis, H. capsulatum and S. schenckii. Weak staining of mycelial forms
      of P. brasiliensis and hyphae of A. fumigatus was also observed. The availability
      of a monoclonal antibody specific to fungal glucosylceramide, and its potential
      use in analyzing biological roles attributed to glucosylceramide in fungi are
      discussed.

PMID- 11287398
TI  - Characterization of cerebrosides from the thermally dimorphic mycopathogen
      Histoplasma capsulatum: expression of 2-hydroxy fatty N-acyl (E)-Delta(3)
      unsaturation correlates with the yeast-mycelium phase transition.
AB  - Cerebroside (monohexosylceramide) components were identified in neutral lipids
      extracted from both the yeast and mycelial forms of the thermally dimorphic
      mycopathogen Histoplasma capsulatum. The components were purified from both forms
      and their structures elucidated by 1- and 2-dimensional nuclear magnetic
      resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS),
      and low energy tandem collision-induced dissociation mass spectrometry (ESI
      MS/CID-MS). Both components were characterized as beta-glucopyranosylceramides
      (GlcCers) containing (4E,8E)-9-methyl-4,8-sphingadienine as the long-chain base,
      attached to 18-carbon 2-hydroxy fatty N-acyl components. However, while the fatty
      acid of the yeast form GlcCer was virtually all N-2'-hydroxyoctadecanoate, the
      mycelium form GlcCer was characterized by almost exclusive expression of N-2'
      hydroxy-(E)-delta(3)-octadecenoate. These results suggest that the yeast-mycelium
      transition is accompanied by up-regulation of an as yet uncharacterized ceramide
      or cerebroside 2-hydroxy fatty N-acyl (E)-delta(3)-desaturase activity. They also
      constitute further evidence for the existence of two distinct pathways for
      ceramide biosynthesis in fungi, since glycosylinositol phosphorylceramides
      (GIPCs), the other major class of fungal glycosphingolipids, are found with
      ceramides consisting of 4-hydroxysphinganine (phytosphingosine) and longer chain
      2-hydroxy fatty acids. In addition to identification of the major
      glucocerebroside components, minor components (< 5%) detectable by molecular
      weight differences in the ESI-MS profiles were also characterized by tandem ESI
      MS/CID-MS analysis. These minor components were identified as variants differing
      in fatty acyl chain length, or the absence of the sphingoid 9-methyl group or (E)
      delta(8)-unsaturation, and are hypothesized to be either biosynthetic
      intermediates or the result of imperfect chemical transformation by the enzymes
      responsible for these features. Possible implications of these findings with
      respect to chemotaxonomy, compartmentalization of fungal glycosphingolipid
      biosynthetic pathways, and regulation of morphological transitions in
      H.capsulatum and other dimorphic fungi are discussed.

PMID- 11287399
TI  - Specificity of carbohydrate structures of gangliosides in the activity to
      regenerate the rat axotomized hypoglossal nerve.
AB  - We previously reported that a ganglioside mixture from bovine brain could prevent
      neuronal death and promote regeneration in rats with hypoglossal nerve resection.
      In the present study, we have compared the neurotrophic effects of various
      glycosphingolipids including lactosyl-ceramide. The findings revealed that GT1b
      had the activity of neuronal death prevention equivalent to a ganglioside mixture
      or autograft, while other glycolipids exhibited about 60% activity. However, the
      capability to promote the regeneration varied among glycolipids, that is, GT1b
      (86%), GD1b (55%), GD1a (35%), GQ1b (34%), GM1 (20%), lactosyl-ceramide (17%) in
      the number of horseradish peroxidase-positive neurons as an indicator of
      regeneration. The experiments with oligosaccharides of GT1b or GD1b and ceramide
      showed that the carbohydrate moiety mainly exerts neurotrophic effects. These
      findings suggested that fine structures of carbohydrate moiety in gangliosides
      are critical in the regenerative activity in this hypoglossal nerve regeneration
      system.

PMID- 11287400
TI  - Structure and properties of the exopolysaccharide produced by Streptococcus
      macedonicus Sc136.
AB  - Streptococcus macedonicus is a Gram positive lactic acid bacterium that is part
      of the starter flora present in Greek sheep and goat cheeses. The S. macedonicus
      Sc136 strain produces a high-molecular-mass, highly texturizing exopolysaccharide
      composed of D-glucose, D-galactose, and N-acetyl-D-glucosamine in the molar ratio
      of 3:2:1. The structure of the exopolysaccharide produced by S. macedonicus Sc136
      was determined by chemical analysis, mass spectrometry, and nuclear magnetic
      resonance spectroscopy. The repeating unit was shown to be: (see text) The
      polysaccharide sidechain beta-D-Galf-(1-->6)-beta-D-Glcp-(1-->6)-beta-D-GlcpNAc
      is a key factor in the highly texturizing properties of the S.macedonicus Sc136
      exopolysaccharide. Finally, the trisaccharide sequence beta-D-GlcpNAc-(1-->3)
      beta-D-Galp-(1-->4)-beta-D-Glcp corresponds to the internal backbone of the lacto
      N-tetraose and lacto-N-neotetraose units, which serve as a structural basis for
      the large majority of human milk oligosaccharides, an additional property
      offering an important potential for the development of improved infant nutrition
      products.

PMID- 11287401
TI  - Rapid determination of the binding affinity and specificity of the mushroom
      Polyporus squamosus lectin using frontal affinity chromatography coupled to
      electrospray mass spectrometry.
AB  - The binding affinity and specificity of the mushroom Polyporus squamosus lectin
      has been determined by the recently developed method of frontal affinity
      chromatography coupled to electrospray mass spectrometry (FAC/MS). A micro-scale
      affinity column was prepared by immobilizing the lectin ( approximately 25
      microg) onto porous glass beads in a tubing column (9.8 microl column volume).
      The column was then used to screen several oligosaccharide mixtures. The
      dissociation constants of 22 sialylated or sulfated oligosaccharides were
      evaluated against the immobilized lectin. The lectin was found to be highly
      specific for Neu5Acalpha2-6Galbeta1-4Glc/GlcNAc containing oligosaccharides with
      K(d) values near 10 microM. The FAC/MS assay permits the rapid determination of
      the dissociation constants of ligands as well as a higher throughput screening of
      compound mixtures, making it a valuable tool for affinity studies, especially for
      testing large numbers of compounds.

PMID- 11287402
TI  - Characteristic structural features of schistosome cercarial N-glycans: expression
      of Lewis X and core xylosylation.
AB  - Schistosomal egg N-glycans are the only examples in nature that have been
      structurally shown to contain beta2-xylosylation, alpha6-fucosylation, and alpha3
      fucosylation on the N,N'-diacetyl chitobiose core. We present evidence that core
      difucosylated and xylosylated N-glycans are characteristics of Schistosoma
      japonicum eggs but not of the cercariae and adults, for which neither core
      xylosylation nor alpha3-fucosylation could be readily detected. In contrast, a
      majority of the N-glycans from Schistosoma mansoni cercariae but not the adults
      are core xylosylated. Tandem mass spectrometry analysis coupled with
      chromatographic mapping, sequential exoglycosidase digestion, and methylation
      analysis were employed to unambiguously define the structures of core beta2
      xylosylated, alpha6-fucosylated N-glycans from S. mansoni cercariae.
      Unexpectedly, a majority of these N-glycans were found to carry Lewis X
      determinant, Galbeta1-->4(Fucalpha1-->3)GlcNAcbeta1-->, on the nonreducing
      termini of mono- and biantennary structures. The Lewis X-containing glycoproteins
      were found to be distinct from those carrying the complex, multifucosylated
      glycocalyx O-glycans reported previously. The corresponding N-glycans from S.
      japonicum cercariae are likewise dominated by Lewis X termini but without the
      core xylosylation. We concluded that the invading cercariae present an important
      and abundant source of Lewis X antigens, which may contribute to the induced
      humoral response upon infection. Following transformation and development into
      the adults, the N-glycans synthesized comprise a significantly larger amount of
      high mannose and fucosylated pauci-mannose structures in comparison with the
      cercarial N-glycans. A portion of the mono- and biantennary complex types were
      identified to carry Lewis X and fucosylated LacdiNAc termini, which could also be
      detected by mass spectrometry analysis on larger, complex-type structures.

PMID- 11287403
TI  - Ectopic expression of alpha1,6 fucosyltransferase in mice causes steatosis in the
      liver and kidney accompanied by a modification of lysosomal acid lipase.
AB  - The alpha1,6 fucosyltransferase (alpha1,6 FucT) catalyzes the transfer of a
      fucose from GDP-fucose to the innermost GlcNAc residue of N-linked glycans via an
      alpha1,6 linkage. alpha1,6 FucT was overexpressed in transgenic mice under the
      control of a combined cytomegalovirus and chicken beta-actin promoter.
      Histologically numerous small vacuoles, in which lipid droplets had accumulated,
      were observed in hepatocytes and proximal renal tubular cells. Electron
      microscopic studies showed that the lipid droplets were membrane-bound and
      apparently localized within the lysosomes. Cholesterol esters and triglycerides
      were significantly increased in liver and kidney of the transgenic mice. Liver
      lysosomal acid lipase (LAL) activity was significantly lower in the transgenic
      mice compared to the wild mice, whereas LAL protein level, which was detected
      immunochemically, was increased, indicating that the specific activity of LAL was
      much lower in the transgenic mice. In all of the transgenic and nontransgenic
      mice examined, the activity of liver LAL was negatively correlated with the level
      of alpha1,6 FucT activity. As evidenced by lectin and immunoblot analysis, LAL
      was found to be more fucosylated in the transgenic mice, suggesting that the
      aberrant fucosylation of LAL causes an accumulation of inactive LAL in the
      lysosomes. Such an accumulation of inactive LAL could be a likely cause for a
      steatosis in the lysosomes of the liver and kidney in the case of the alpha1,6
      FucT transgenic mice.

PMID- 11287404
TI  - Short-term inpatient pharmacotherapy of schizophrenia.
AB  - There is much practice variation in the pharmacotherapy of schizophrenia on short
      term acute inpatient units, where the length of stay may be 1 week or less. We
      surveyed relevant practice guidelines, review articles, and individual studies
      and developed summary statements regarding evidence-supported procedures for
      short-term inpatient stabilization. If the patient requires parenteral treatment,
      the combination of intramuscular haloperidol 2-5 mg and lorazepam has the
      earliest effect. For initial oral treatment, monotherapy with one of the new
      "atypical" antipsychotics is favored. Some evidence suggests that risperidone may
      have an earlier onset of action. Olanzapine seems to have a relatively more rapid
      effect when started at a daily dose of 15 mg, rather than 5 or 10 mg. The role of
      quetiapine is somewhat unclear. In the event of nonresponse to the initial
      antipsychotic after 3-7 days, alternatives may include increasing the dose,
      switching to a different antipsychotic, or adding a mood stabilizer.

PMID- 11287405
TI  - Day treatment for personality disorders: a review of research findings.
AB  - Day treatment, a form of partial hospitalization, may have unique advantages in
      the care of patients with personality disorders. It appears to offer a favorable
      level of intensiveness and containment, thus facilitating treatment of the
      chronic emotional and behavioral difficulties experienced by these individuals.
      Although several authors have written about the appropriateness of day treatment
      for personality disorder patients, empirical support has been slow to accumulate.
      More recently, greater research attention has been focused on this question. This
      review examines the current research. The findings suggest that day treatment is
      effective for this difficult patient population and that it is more effective
      than standard treatment (i.e., medication and support). Preliminary evidence
      indicates that day treatment may lead to a reduction in future health-services
      costs. Some findings also show that day treatment may be particularly beneficial
      for certain patients-for example, those who are more psychologically minded.
      Implications of these findings for clinical practice are considered. Limitations
      in our current approach to research in this area are highlighted, and
      recommendations for future study are provided.

PMID- 11287406
TI  - The advanced practice of psychotherapy.
AB  - The advanced practice of psychotherapy involves deconstructing and transcending
      separate schools in the search for universal healing processes. Knowledge from
      major psychotherapeutic schools over the last 100 years, as well as ancient
      teachings over the last 5000 years, is distilled in the training and formation of
      the psychotherapist. Five major elements of training (theory, technique, the
      patient, the therapist, and the patient/therapist relationship), as well as one
      element in the therapist's formation (the person), are presented. To be a true
      healer, the clinician must cultivate his or her soul and spirit. Only then can
      the therapist guide the patient to reach his or her authentic self.

PMID- 11287408
TI  - Law and psychiatry: what should our residents learn?

PMID- 11287407
TI  - A case of factitious disorder by proxy: the role of the health-care system,
      diagnostic dilemmas, and family dynamics.

PMID- 11287409
TI  - Is assertive community treatment ethical care?

PMID- 11287410
TI  - Is depression and the parenting of young children a women's issue?

PMID- 11287411
TI  - Ikappa b-alpha, the NF-kappa B inhibitory subunit, interacts with ANT, the
      mitochondrial ATP/ADP translocator.
AB  - The transcription factor NF-kappaB regulates a wide set of genes involved in the
      establishment of many cellular processes that control cell activation,
      proliferation, and apoptosis. IkappaB inhibitory subunits integrate NF-kappaB
      activation signals through phosphorylation and ubiquitination of its N-terminal
      domain. Using the two-hybrid system in yeast, we searched for IkappaB-alpha N
      terminal domain interactors and therefore potential NF-kappaB regulators. An
      interaction of IkappaB-alpha with the mitochondrial ATP/ADP translocator ANT was
      detected in yeast and confirmed in glutathione S-transferase pull-down assays and
      co-precipitation experiments in transfected cells. Subcellular cell
      fractionation, resistance to proteinase K treatment, and electron microscopy
      experiments demonstrated the presence of IkappaB-alpha and associated p65 NF
      kappaB in the mitochondrial intermembrane space. IkappaB-alpha.NF-kappaB appeared
      to be released from mitochondria upon the induction of apoptosis by engagement of
      the Fas receptor. These data suggest that the mitochondrial IkappaB-alpha.NF
      kappaB pool participates in the regulation of apoptosis.

PMID- 11287412
TI  - Regulation of the Src homology 2-containing inositol 5-phosphatase SHIP1 in
      HIP1/PDGFbeta R-transformed cells.
AB  - It has been shown previously that the Huntingtin interacting protein 1 gene
      (HIP1) was fused to the platelet-derived growth factor beta receptor gene
      (PDGFbetaR) in leukemic cells of a patient with chronic myelomonocytic leukemia.
      This resulted in the expression of the chimeric HIP1/PDGFbetaR protein, which
      oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the Ba/F3
      murine hematopoietic cell line to interleukin-3-independent growth. Tyrosine
      phosphorylation of a 130-kDa protein (p130) correlates with transformation by
      HIP1/PDGFbetaR and related transforming mutants. We report here that the p130
      band is immunologically related to the 125-kDa isoform of the Src homology 2
      containing inositol 5-phosphatase, SHIP1. We have found that SHIP1 associates and
      colocalizes with the HIP1/PDGFbetaR fusion protein and related transforming
      mutants. These mutants include a mutant that has eight Src homology 2-binding
      phosphotyrosines mutated to phenylalanine. In contrast, SHIP1 does not associate
      with H/P(KI), the kinase-dead form of HIP1/PDGFbetaR. We also report that
      phosphorylation of SHIP1 by HIP1/PDGFbetaR does not change its 5-phosphatase
      specific activity. This suggests that phosphorylation and possible PDGFbetaR
      mediated sequestration of SHIP1 from its substrates (PtdIns(3,4,5)P(3) and
      Ins(1,3,4,5)P(4)) might alter the levels of these inositol-containing signal
      transduction molecules, resulting in activation of downstream effectors of
      cellular proliferation and/or survival.

PMID- 11287413
TI  - Sustained activation of extracellular signal-regulated kinase stimulated by
      hepatocyte growth factor leads to integrin alpha 2 expression that is involved in
      cell scattering.
AB  - We have previously shown that hepatocyte growth factor (HGF) selectively
      increases the expression of integrin alpha(2) in Madin-Darby canine kidney (MDCK)
      cells. In this study, we have further investigated the signal transduction
      pathways responsible for the event and its role in HGF-induced cell scattering.
      We found that the level of integrin alpha(2)beta(1) expression induced by HGF
      correlated with the extent of cell scattering and that a functional blocking
      antibody against integrin alpha(2) at the concentration of 25 microg/ml partially
      (40%) inhibited the HGF-induced cell scattering. However, in the presence of the
      specific phosphatidylinositol 3-kinase inhibitor LY294002 or the selective Src
      family kinase inhibitor PP1, although cells retained their response to HGF for
      increasing integrin alpha(2) expression, they failed to scatter, indicating that
      increased expression of integrin alpha(2) alone is not sufficient for cell
      scattering. Moreover, epidermal growth factor, which induced a transient (1 h)
      activation of extracellular signal-regulated kinase (ERK) in MDCK cells, only
      slightly increased integrin alpha(2) expression and failed to trigger cell
      scattering. Conversely, HGF induced a sustained (at least 12 h) activation of ERK
      in the cells. Expression of constitutively active ERK kinase (MEK) in MDCK cells
      led to increased expression of integrin alpha(2) even in the absence of HGF
      stimulation. In contrast, expression of ERK phosphatase or dominant negative MEK
      inhibited HGF-induced integrin alpha(2) expression. Taken together, our results
      suggest that the increased expression of integrin alpha(2)beta(1) by HGF is at
      least partially required for cell scattering and that the duration of MEK/ERK
      activation is likely to be a crucial determinant for cells to activate integrin
      alpha(2) expression and cell scattering.

PMID- 11287414
TI  - Class I major histocompatibility complex anchor substitutions alter the
      conformation of T cell receptor contacts.
AB  - An immunogenic peptide (GP2) derived from HER-2/neu binds to HLA-A2.1 very
      poorly. Some altered-peptide ligands (APL) of GP2 have increased binding affinity
      and generate improved cytotoxic T lymphocyte recognition of GP2-presenting tumor
      cells, but most do not. Increases in binding affinity of single-substitution APL
      are not additive in double-substitution APL. A common first assumption about
      peptide binding to class I major histocompatibility complex is that each residue
      binds independently. In addition, immunologists interested in immunotherapy
      frequently assume that anchor substitutions do not affect T cell receptor contact
      residues. However, the crystal structures of two GP2 APL show that the central
      residues change position depending on the identity of the anchor residue(s).
      Thus, it is clear that subtle changes in the identity of anchor residues may have
      significant effects on the positions of the T cell receptor contact residues.

PMID- 11287415
TI  - A point mutation in nucleoside diphosphate kinase results in a deficient light
      response for perithecial polarity in Neurospora crassa.
AB  - In Neurospora crassa, the phosphorylation of nucleoside diphosphate kinase (NDK)
      1 is rapidly enhanced after blue light irradiation. We have investigated the
      function of NDK-1 in the blue light signal transduction pathway. A mutant called
      psp (phosphorylation of small protein) shows undetectable phosphorylation of NDK
      1 and is defective in light-responsive regulation of perithecial polarity.
      Sequencing analysis of ndk-1 cDNA by reverse transcription-polymerase chain
      reaction revealed that proline 72 of ndk-1 was replaced with histidine in psp.
      The mutation ndk-1(P72H) resulted in accumulation of normal levels of mRNA and of
      about 25% of NDK-1(P72H) protein compared with that of wild type as determined by
      Western blot analysis. The ectopic expression of cDNA and introduction of genomic
      DNA of wild type ndk-1 in psp (ndk-1(P72H)) suppressed the reduction in
      accumulation and phosphorylation of NDK-1 and the light-insensitive phenotype.
      These findings demonstrated that the phenotype of psp was caused by the ndk
      1(P72H) mutation. Biochemical analysis using recombinant NDK-1 and NDK-1(P72H)
      indicated that the P72H substitution in NDK-1 was responsible for the decrease in
      phosphotransfer activities, 5% of autophosphorylation activity, and 2% of V(max)
      for protein kinase activity phosphorylating myelin basic protein, compared with
      those of wild type NDK-1, respectively.

PMID- 11287416
TI  - ERK7 is an autoactivated member of the MAPK family.
AB  - Extracellular signal-regulated kinase 7 (ERK7) shares significant sequence
      homology with other members of the ERK family of signal transduction proteins,
      including the signature TEY activation motif. However, ERK7 has several
      distinguishing characteristics. Unlike other ERKs, ERK7 has been shown to have
      significant constitutive activity in serum-starved cells, which is not increased
      further by extracellular stimuli that typically activate other members of the
      mitogen-activated protein kinase (MAPK) family. On the other hand, ERK7's
      activation state and kinase activity appear to be regulated by its ability to
      utilize ATP and the presence of its extended C-terminal region. In this study, we
      investigated the mechanism of ERK7 activation. The results suggest that 1) MAPK
      kinase (MEK) inhibitors do not suppress ERK7 kinase activity; 2) intramolecular
      autophosphorylation is sufficient for activation of ERK7 in the absence of an
      upstream MEK; and 3) multiple regions of the C-terminal domain of ERK7 regulate
      its kinase activity. Taken together, these results indicate that
      autophosphorylation is sufficient for ERK7 activation and that the C-terminal
      domain regulates its kinase activity through multiple interactions.

PMID- 11287417
TI  - Mapping the hyaluronan-binding site on the link module from human tumor necrosis
      factor-stimulated gene-6 by site-directed mutagenesis.
AB  - Link modules are hyaluronan-binding domains found in extracellular proteins
      involved in matrix assembly, development, and immune cell migration. Previously
      we have expressed the Link module from the inflammation-associated protein tumor
      necrosis factor-stimulated gene-6 (TSG-6) and determined its tertiary structure
      in solution. Here we generated 21 Link module mutants, and these were analyzed by
      nuclear magnetic resonance spectroscopy and a hyaluronan-binding assay. The
      individual mutation of five amino acids, which form a cluster on one face of the
      Link module, caused large reductions in functional activity but did not affect
      the Link module fold. This ligand-binding site in TSG-6 is similar to that
      determined previously for the hyaluronan receptor, CD44, suggesting that the
      location of the interaction surfaces may also be conserved in other Link module
      containing proteins. Analysis of the sequences of TSG-6 and CD44 indicates that
      the molecular details of their association with hyaluronan are likely to be
      significantly different. This comparison identifies key sequence positions that
      may be important in mediating hyaluronan binding, across the Link module
      superfamily. The use of multiple sequence alignment and molecular modeling
      allowed the prediction of functional residues in link protein, and this approach
      can be extended to all members of the superfamily.

PMID- 11287418
TI  - Functionally similar vanadate-induced 8-azidoadenosine 5'-[alpha
      (32)P]Diphosphate-trapped transition state intermediates of human P-glycoprotin
      are generated in the absence and presence of ATP hydrolysis.
AB  - P-glycoprotein (Pgp) is an ATP-dependent drug efflux pump whose overexpression
      confers multidrug resistance to cancer cells. Pgp exhibits a robust drug
      substrate-stimulable ATPase activity, and vanadate (Vi) blocks this activity
      effectively by trapping Pgp nucleotide in a non-covalent stable transition state
      conformation. In this study we compare Vi-induced [alpha-(32)P]8-azido-ADP
      trapping into Pgp in the presence of [alpha-(32)P]8-azido-ATP (with ATP
      hydrolysis) or [alpha-(32)P]8-azido-ADP (without ATP hydrolysis). Vi mimics P(i)
      to trap the nucleotide tenaciously in the Pgp.[alpha-(32)P]8-azido-ADP.Vi
      conformation in either condition. Thus, by using [alpha-(32)P]8-azido-ADP we show
      that the Vi-induced transition state of Pgp can be generated even in the absence
      of ATP hydrolysis. Furthermore, half-maximal trapping of nucleotide into Pgp in
      the presence of Vi occurs at similar concentrations of [alpha-(32)P]8-azido-ATP
      or [alpha-(32)P]8-azido-ADP. The trapped [alpha-(32)P]8-azido-ADP is almost
      equally distributed between the N- and the C-terminal ATP sites of Pgp in both
      conditions. Additionally, point mutations in the Walker B domain of either the N-
      (D555N) or C (D1200N)-terminal ATP sites that arrest ATP hydrolysis and Vi
      induced trapping also show abrogation of [alpha-(32)P]8-azido-ADP trapping into
      Pgp in the absence of hydrolysis. These data suggest that both ATP sites are
      dependent on each other for function and that each site exhibits similar affinity
      for 8-azido-ATP (ATP) or 8-azido-ADP (ADP). Similarly, Pgp in the transition
      state conformation generated with either ADP or ATP exhibits drastically reduced
      affinity for the binding of analogues of drug substrate
      ([(125)I]iodoarylazidoprazosin) as well as nucleotide (2'(3')-O-(2,4,6
      trinitrophenyl)adenosine 5'-triphosphate). Analyses of Arrhenius plots show that
      trapping of Pgp with [alpha-(32)P]8-azido-ADP (in the absence of hydrolysis)
      displays an approximately 2.5-fold higher energy of activation (152 kJ/mol)
      compared with that observed when the transition state intermediate is generated
      through hydrolysis of [alpha-(32)P]8-azido-ATP (62 kJ/mol). In aggregate, these
      results demonstrate that the Pgp.[alpha-(32)P]8-azido-ADP (or ADP).Vi transition
      state complexes generated either in the absence of or accompanying [alpha-(32)P]8
      azido-ATP hydrolysis are functionally indistinguishable.

PMID- 11287419
TI  - CYR61 stimulates human skin fibroblast migration through Integrin alpha vbeta 5
      and enhances mitogenesis through integrin alpha vbeta 3, independent of its
      carboxyl-terminal domain.
AB  - CYR61, an angiogenic factor and a member of the CCN protein family, is an
      extracellular matrix-associated, heparin-binding protein that mediates cell
      adhesion, promotes cell migration, and enhances growth factor-stimulated cell
      proliferation. CYR61 induces angiogenesis and promotes tumor growth in vivo and
      is expressed in dermal fibroblasts during cutaneous wound healing. It has been
      demonstrated recently that adhesion of primary skin fibroblasts to CYR61 is
      mediated through integrin alpha(6)beta(1) and cell surface heparan sulfate
      proteoglycans, resulting in adhesive signaling and up-regulation of matrix
      metalloproteinases 1 and 3. CYR61 is composed of four discrete structural domains
      that bear sequence similarities to the insulin-like growth factor-binding
      proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and
      a carboxyl-terminal (CT) domain that resembles cysteine knots found in some
      growth factors. In this study, we show that a CYR61 mutant (CYR61DeltaCT) that
      has the CT domain deleted is unable to support adhesion of primary human skin
      fibroblasts but is still able to stimulate chemotaxis and enhance basic
      fibroblast growth factor-induced mitogenesis similar to wild type. In addition,
      fibroblast migration to CYR61 is mediated through integrin alpha(v)beta(5) but
      not integrins alpha(6)beta(1) or alpha(v)beta(3). Furthermore, we show that CYR61
      binds directly to purified integrin alpha(v)beta(5) in vitro. By contrast, CYR61
      enhancement of basic fibroblast growth factor-induced DNA synthesis is mediated
      through integrin alpha(v)beta(3), a known receptor for CYR61 that mediates CYR61
      dependent cell adhesion and chemotaxis in vascular endothelial cells. Thus, CYR61
      promotes primary human fibroblast adhesion, migration, and mitogenesis through
      integrins alpha(6)beta(1), alpha(v)beta(5), and alpha(v)beta(3), respectively.
      Together, these findings establish CYR61 as a novel ligand for integrin
      alpha(v)beta(5) and show that CYR61 interacts with distinct integrins to mediate
      disparate activities in a cell type-specific manner.

PMID- 11287420
TI  - Interaction of the hepatitis B virus X protein with the Crm1-dependent nuclear
      export pathway.
AB  - The leucine-rich nuclear export signal (NES) is used to shuttle large cellular
      proteins from the nucleus to the cytoplasm. The nuclear export receptor Crm1 is
      essential in this process by recognizing the NES motif. Here, we show that the
      oncogenic hepatitis B virus (HBV) X protein (HBx) contains a functional NES
      motif. We found that the predominant cytoplasmic localization of HBx is sensitive
      to the drug leptomycin B (LMB), which specifically inactivates Crm1. Mutations at
      the two conserved leucine residues to alanine at the NES motif (L98A,L100A)
      resulted in a nuclear redistribution of HBx. A recombinant HBx protein binds to
      Crm1 in vitro. In addition, ectopic expression of HBx sequesters Crm1 in the
      cytoplasm. Furthermore, HBx activates NFkappaB by inducing its nuclear
      translocation in a NES-dependent manner. Abnormal cytoplasmic sequestration of
      Crm1, accompanied by a nuclear localization of NFkappaB, was also observed in
      hepatocytes from HBV-positive liver samples with chronic active hepatitis. We
      suggest that Crm1 may play a role in HBx-mediated liver carcinogenesis.

PMID- 11287421
TI  - Conserved Kv4 N-terminal domain critical for effects of Kv channel-interacting
      protein 2.2 on channel expression and gating.
AB  - Association of Kv channel-interacting proteins (KChIPs) with Kv4 channels leads
      to modulation of these A-type potassium channels (An, W. F., Bowlby, M. R.,
      Betty, M., Cao, J., Ling, H. P., Mendoza, G., Hinson, J. W., Mattsson, K. I.,
      Strassle, B. W., Trimmer, J. S., and Rhodes, K. J. (2000) Nature 403, 553-556).
      We cloned a KChIP2 splice variant (KChIP2.2) from human ventricle. In comparison
      with KChIP2.1, coexpression of KChIP2.2 with human Kv4 channels in mammalian
      cells slowed the onset of Kv4 current inactivation (2-3-fold), accelerated the
      recovery from inactivation (5-7-fold), and shifted Kv4 steady-state inactivation
      curves by 8-29 mV to more positive potentials. The features of Kv4.2/KChIP2.2
      currents closely resemble those of cardiac rapidly inactivating transient outward
      currents. KChIP2.2 stimulated the Kv4 current density in Chinese hamster ovary
      cells by approximately 55-fold. This correlated with a redistribution of
      immunoreactivity from perinuclear areas to the plasma membrane. Increased Kv4
      cell-surface expression and current density were also obtained in the absence of
      KChIP2.2 when the highly conserved proximal Kv4 N terminus was deleted. The same
      domain is required for association of KChIP2.2 with Kv4 alpha-subunits. We
      propose that an efficient transport of Kv4 channels to the cell surface depends
      on KChIP binding to the Kv4 N-terminal domain. Our data suggest that the binding
      is necessary, but not sufficient, for the functional activity of KChIPs.

PMID- 11287422
TI  - Isolation and characterization of major glycoproteins of pigeon egg white:
      ubiquitous presence of unique N-glycans containing Galalpha1-4Gal.
AB  - Ovotransferrin (POT), two ovalbumins (POA(hi) and POA(lo)), and ovomucoid (POM)
      were isolated from pigeon egg white (PEW). Unlike their chicken egg white
      counterparts, PEW glycoproteins contain terminal Galalpha1-4Gal, as evidenced by
      GS-I lectin (specific for terminal alpha-Gal), anti-P(1) (Galalpha1-4Galbeta1
      4GlcNAcbeta1-3Galbeta1-4Glcbeta1-1Cer) monoclonal antibody, and P fimbriae on
      uropathogenic Escherichia coli (specific for Galalpha1-4Gal). Galalpha1-4Gal on
      PEW glycoproteins were found in N-glycans releasable by treatment with
      glycoamidase F. The respective contents of N-glycans in each glycoprotein were
      3.5%, POT; 17%, POA(hi); and 31-37%, POM. POA(hi) has four N-glycosylation sites,
      in contrast to chicken ovalbumin, which has only one. High performance liquid
      chromatography analysis showed that N-glycans on POA(hi) were highly
      heterogeneous. Mass spectrometric analysis revealed that the major N-glycans were
      monosialylated tri-, tetra-, and penta-antennary oligosaccharides containing
      terminal Galalpha1-4Gal with or without bisecting N-acetylglucosamine.
      Oligosaccharide chains terminating in Galalpha1-4Gal are rare among N-glycans
      from the mammals and avians that have been studied, and our finding is the first
      predominant presence of (Galalpha1-4Gal)-terminated N-glycans.

PMID- 11287423
TI  - Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying
      potassium channel, Kir2.1.
AB  - Protein kinase A (PKA) is targeted to discrete subcellular locations close to its
      intended substrates through interaction with A kinase-anchoring proteins (AKAPs).
      Ion channels represent a diverse and important group of kinase substrates, and it
      has been shown that membrane targeting of PKA through association with AKAPs
      facilitates PKA-mediated phosphorylation and regulation of several classes of ion
      channel. Here, we investigate the effect of AKAP79, a membrane-associated
      multivalent-anchoring protein, upon the function and modulation of the strong
      inwardly rectifying potassium channel, Kir2.1. Functionally, the presence of
      AKAP79 enhanced the response of Kir2.1 to elevated intracellular cAMP, suggesting
      a requirement for a pool of PKA anchored close to the channel. Antibodies
      directed against a hemagglutinin epitope tag on Kir2.1 coimmunoprecipitated
      AKAP79, indicating that the two proteins exist together in a complex within
      intact cells. In support of this, glutathione S-transferase fusion proteins of
      both the intracellular N and C domains of Kir2.1 isolated AKAP79 from cell
      lysates, while glutathione S-transferase alone failed to interact with AKAP79.
      Together, these findings suggest that AKAP79 associates directly with the Kir2.1
      ion channel and may serve to anchor kinase enzymes in close proximity to key
      channel phosphorylation sites.

PMID- 11287424
TI  - Aggretin, a heterodimeric C-type lectin from Calloselasma rhodostoma (Malayan pit
      viper), stimulates platelets by binding to alpha2beta1 integrin and glycoprotein
      Ib, activating Syk and phospholipase Cgamma 2, but does not involve the
      glycoprotein VI/Fc receptor gamma chain collagen receptor.
AB  - Aggretin, a potent platelet activator, was isolated from Calloselasma rhodostoma
      venom, and 30-amino acid N-terminal sequences of both subunits were determined.
      Aggretin belongs to the heterodimeric snake C-type lectin family and is thought
      to activate platelets by binding to platelet glycoprotein alpha(2)beta(1). We now
      show that binding to glycoprotein (GP) Ib is also required. Aggretin-induced
      platelet activation was inhibited by a monoclonal antibody to GPIb as well as by
      antibodies to alpha(2)beta(1). Binding of both of these platelet receptors to
      aggretin was confirmed by affinity chromatography. No binding of other major
      platelet membrane glycoproteins, in particular GPVI, to aggretin was detected.
      Aggretin also activates platelets from Fc receptor gamma chain (Fcgamma)
      deficient mice to a greater extent than those from normal control mice, showing
      that it does not use the GPVI/Fcgamma pathway. Platelets from Fcgamma-deficient
      mice expressed fibrinogen receptors normally in response to collagen, although
      they did not aggregate, indicating that these platelets may partly compensate via
      other receptors including alpha(2)beta(1) or GPIb for the lack of the Fcgamma
      pathway. Signaling by aggretin involves a dose-dependent lag phase followed by
      rapid tyrosine phosphorylation of a number of proteins. Among these are p72(SYK),
      p125(FAK), and PLCgamma2, whereas, in comparison with collagen and convulxin, the
      Fcgamma subunit neither is phosphorylated nor coprecipitates with p72(SYK). This
      supports an independent, GPIb- and integrin-based pathway for activation of
      p72(SYK) not involving the Fcgamma receptor.

PMID- 11287425
TI  - Stimulation of human endonuclease III by Y box-binding protein 1 (DNA-binding
      protein B). Interaction between a base excision repair enzyme and a transcription
      factor.
AB  - Human endonuclease III (hNth1) is a DNA glycosylase/apurinic/apyrimidinic (AP)
      lyase that initiates base excision repair of pyrimidines modified by reactive
      oxygen species, ionizing, and ultraviolet radiation. Using duplex 2'-deoxyribose
      oligonucleotides containing an abasic (AP) site, a thymine glycol, or a 5
      hydroxyuracil residue as substrates, we found the AP lyase activity of hNth1 was
      7 times slower than its DNA glycosylase activity, similar to results reported for
      murine and human 8-oxoguanine-DNA glycosylase, which are also members of the
      endonuclease III family. This difference in rates contrasts with the equality of
      rates found in Escherichia coli and Saccharomyces cerevisiae endonuclease III
      homologs. A yeast two-hybrid screen for potential modulators of hNth1 activity
      revealed interaction with the damage-inducible transcription factor Y box-binding
      protein 1 (YB-1), also identified as DNA-binding protein B (DbpB). The in vitro
      addition of His(6)YB-1 to hNth1 increased the rate of DNA glycosylase and AP
      lyase activity. Analysis revealed that YB-1 affects the steady state equilibrium
      between the covalent hNth1-AP site Schiff base ES intermediate and the
      noncovalent ES intermediate containing the AP aldehydic sugar and the epsilon
      amino group of the hNth1 active site lysine. This equilibrium may be a checkpoint
      in modulating hNth1 activity.

PMID- 11287426
TI  - Allergic cross-reactivity made visible: solution structure of the major cherry
      allergen Pru av 1.
AB  - Birch pollinosis is often accompanied by hypersensitivity to fruit as a
      consequence of the cross-reaction of pollen allergen-specific IgE antibodies with
      homologous food proteins. To provide a basis for examining the cross-reactivity
      on a structural level, we used heteronuclear multidimensional NMR spectroscopy to
      determine the high-resolution three-dimensional structure of the major cherry
      allergen, Pru av 1, in solution. Based on a detailed comparison of the virtually
      identical structures of Pru av 1 and Bet v 1, the major birch pollen allergen, we
      propose an explanation for a significant aspect of the observed cross-reactivity
      pattern among the family of allergens under consideration. The large hydrophobic
      cavity expected to be important for the still unknown physiological function of
      Bet v 1 is conserved in Pru av 1. Structural homology to a domain of human MLN64
      associated with cholesterol transport suggests phytosteroids as putative ligands
      for Pru av 1. NMR spectroscopy provides experimental evidence that Pru av 1
      interacts with phytosteroids, and molecular modeling shows that the hydrophobic
      cavity is large enough to accommodate two such molecules.

PMID- 11287427
TI  - Molecular cloning of a novel lipocalin-1 interacting human cell membrane receptor
      using phage display.
AB  - Human lipocalin-1 (Lcn-1, also called tear lipocalin), a member of the lipocalin
      structural superfamily, is produced by a number of glands and tissues and is
      known to bind an unusually large array of hydrophobic ligands. Apart from its
      specific function in stabilizing the lipid film of human tear fluid, it is
      suggested to act as a physiological scavenger of potentially harmful lipophilic
      compounds, in general. To characterize proteins involved in the reception,
      detoxification, or degradation of these ligands, a cDNA phage-display library
      from human pituitary gland was constructed and screened for proteins interacting
      with Lcn-1. Using this method an Lcn-1 interacting phage was isolated that
      expressed a novel human protein. Molecular cloning and analysis of the entire
      cDNA indicated that it encodes a 55-kDa protein, lipocalin-1 interacting membrane
      receptor (LIMR), with nine putative transmembrane domains. The cell membrane
      location of this protein was confirmed by immunocytochemistry and Western blot
      analysis of membrane fractions of human NT2 cells. Independent biochemical
      investigations using a recombinant N-terminal fragment of LIMR also demonstrated
      a specific interaction with Lcn-1 in vitro. Based on these data, we suggest LIMR
      to be a receptor of Lcn-1 ligands. These findings constitute the first report of
      cloning of a lipocalin interacting, plasma membrane-located receptor, in general.
      In addition, a sequence comparison supports the biological relevance of this
      novel membrane protein, because genes with significant nucleotide sequence
      similarity are present in Takifugu rubripes, Drosophila melanogaster,
      Caenorhabditis elegans, Mus musculus, Bos taurus, and Sus scrofa. According to
      data derived from the human genome sequencing project, the LIMR-encoding gene has
      to be mapped on human chromosome 12, and its intron/exon organization could be
      established. The entire LIMR-encoding gene consists of about 13.7 kilobases in
      length and contains 16 introns with a length between 91 and 3438 base pairs.

PMID- 11287428
TI  - Ceramide enables fas to cap and kill.
AB  - Recent studies suggest that trimerization of Fas is insufficient for apoptosis
      induction and indicate that super-aggregation of trimerized Fas might be
      prerequisite. For many cell surface receptors, cross-linking by multivalent
      ligands or antibodies induces their lateral segregation within the plasma
      membrane and co-localization into "caps" on one pole of the cell. In this study,
      we show that capping of Fas is essential for optimal function and that capping is
      ceramide-dependent. In Jurkat T lymphocytes and in primary cultures of
      hepatocytes, ceramide elevation was detected as early as 15-30 s and peaked at 1
      min after CH-11 and Jo2 anti-Fas antibody treatment, respectively. Capping was
      detected 30 s after Fas ligation, peaked at 2 min, and was maintained at a lower
      level for as long as 30 min in both cell types. Ceramide generation appeared
      essential for capping. Acid sphingomyelinase -/- hepatocytes were defective in
      Jo2-induced ceramide generation, capping, and apoptosis, and nanomolar
      concentrations of C(16)-ceramide restored these events. To further explore the
      role of ceramide in capping of Fas, we employed FLAG-tagged soluble Fas ligand
      (sFasL), which binds trimerized Fas but is unable to induce capping or apoptosis
      in Jurkat cells. Cross-linking of sFasL with M2 anti-FLAG antibody induced both
      events. Pretreatment of cells with natural C(16)-ceramide bypassed the necessity
      for forced antibody cross-linking and enabled sFasL to cap and kill. The presence
      of intact sphingolipid-enriched membrane domains may be essential for Fas capping
      since their disruption with cholesterol-depleting agents abrogated capping and
      prevented apoptosis. These data suggest that capping is a ceramide-dependent
      event required for optimal Fas signaling in some cells.

PMID- 11287429
TI  - Overexpression of gamma-sarcoglycan induces severe muscular dystrophy.
      Implications for the regulation of Sarcoglycan assembly.
AB  - The sarcoglycan complex is found normally at the plasma membrane of muscle.
      Disruption of the sarcoglycan complex, through primary gene mutations in
      dystrophin or sarcoglycan subunits, produces membrane instability and muscular
      dystrophy. Restoration of the sarcoglycan complex at the plasma membrane requires
      reintroduction of the mutant sarcoglycan subunit in a manner that will permit
      normal assembly of the entire sarcoglycan complex. To study sarcoglycan gene
      replacement, we introduced transgenes expressing murine gamma-sarcoglycan into
      muscle of normal mice. Mice expressing high levels of gamma-sarcoglycan, under
      the control of the muscle-specific creatine kinase promoter, developed a severe
      muscular dystrophy with greatly reduced muscle mass and early lethality. Marked
      gamma-sarcoglycan overexpression produced cytoplasmic aggregates that interfered
      with normal membrane targeting of gamma-sarcoglycan. Overexpression of gamma
      sarcoglycan lead to the up-regulation of alpha- and beta-sarcoglycan. These data
      suggest that increased gamma-sarcoglycan and/or mislocalization of gamma
      sarcoglycan to the cytoplasm is sufficient to induce muscle damage and provides a
      new model of muscular dystrophy that highlights the importance of this protein in
      the assembly, function, and downstream signaling of the sarcoglycan complex. Most
      importantly, gene dosage and promoter strength should be given serious
      consideration in replacement gene therapy to ensure safety in human clinical
      trials.

PMID- 11287430
TI  - Purification, characterization, and cloning of the cDNA of human signal
      recognition particle RNA 3'-adenylating enzyme.
AB  - The 3'-terminal adenylic acid residue in several human small RNAs including
      signal recognition particle (SRP) RNA, nuclear 7SK RNA, U2 small nuclear RNA, and
      ribosomal 5S RNA is caused by a post-transcriptional adenylation event (Sinha,
      K., Gu, J., Chen, Y., and Reddy, R. (1998) J. Biol. Chem. 273, 6853-6859). Using
      the Alu portion of the SRP RNA as a substrate in an in vitro adenylation assay,
      we purified an adenylating enzyme that adds adenylic acid residues to SRP/Alu RNA
      from the HeLa cell nuclear extract. All the peptide sequences obtained by
      microsequencing of the purified enzyme matched a unique human cDNA corresponding
      to a new adenylating enzyme having homologies to the well characterized mRNA
      poly(A) polymerase. The amino terminus region of the human SRP RNA adenylating
      enzyme showed approximately 75% homology to the amino terminus of the human mRNA
      poly(A) polymerase that includes the catalytic domain. The carboxyl terminus of
      the human SRP RNA adenylating enzyme showed less than 25% homology to the
      carboxyl terminus of poly(A) polymerase, which interacts with other factors and
      provides specificity. The SRP RNA adenylating enzyme is coded for by a gene
      located on chromosome 2 in contrast to the poly(A) polymerase gene, which is
      located on chromosome 14. A recombinant protein for the SRP RNA adenylating
      enzyme was prepared, and its activity was compared with the purified enzyme from
      HeLa cells. The data indicate that in addition to the SRP RNA adenylating enzyme,
      other factors may be required to carry out accurate 3'-end adenylation of SRP
      RNA.

PMID- 11287431
TI  - Evidence for direct interaction between enzyme I(Ntr) and aspartokinase to
      regulate bacterial oligopeptide transport.
AB  - Bradyrhizobium japonicum transports oligopeptides and the heme precursor delta
      aminolevulinic acid (ALA) by a common mechanism. Two Tn5-induced mutants
      disrupted in the lysC and ptsP genes were identified based on the inability to
      use prolyl-glycyl-glycine as a proline source and were defective in [(14)C]ALA
      uptake activity. lysC and ptsP were shown to be proximal genes in the B.
      japonicum genome. However, RNase protection and in trans complementation analysis
      showed that lysC and ptsP are transcribed separately, and that both genes are
      involved in oligopeptide transport. Aspartokinase, encoded by lysC, catalyzes the
      phosphorylation of aspartate for synthesis of three amino acids, but the lysC
      strain is not an amino acid auxotroph. The ptsP gene encodes Enzyme I(Ntr)
      (EI(Ntr)), a paralogue of Enzyme I of the phosphoenolpyruvate:sugar
      phosphotransferase (PTS) system. In vitro pull-down experiments indicated that
      purified recombinant aspartokinase and EI(Ntr) interact directly with each other.
      Expression of ptsP in trans from a multicopy plasmid complemented the lysC
      mutant, suggesting that aspartokinase normally affects Enzyme I(Ntr) in a manner
      that can be compensated for by increasing the copy number of the ptsP gene. ATP
      was not a phosphoryl donor to purified EI(Ntr), but it was phosphorylated by ATP
      in the presence of cell extracts. This phosphorylation was inhibited in the
      presence of aspartokinase. The findings demonstrate a role for a PTS protein in
      the transport of a non-sugar solute and suggest an unusual regulatory function
      for aspartokinase in regulating the phosphorylation state of EI(Ntr).

PMID- 11287432
TI  - Retinoids for ovarian cancer prevention: laboratory data set the stage for
      thoughtful clinical trials.

PMID- 11287433
TI  - Counting recurrent events in cancer research.

PMID- 11287434
TI  - Are physician-scientists a vanishing breed?

PMID- 11287436
TI  - Microarrays have arrived: gene expression tool matures.

PMID- 11287437
TI  - Draft human genome sequence yields several surprises.

PMID- 11287438
TI  - Lymphoma rate rise continues to baffle researchers.

PMID- 11287440
TI  - Britain implements nationwide cancer standards.

PMID- 11287442
TI  - Lymphangiogenesis explored as potential route for metastasis.

PMID- 11287443
TI  - SEER doubles coverage by adding registries for four states.

PMID- 11287444
TI  - Impact of patient and provider characteristics on the treatment and outcomes of
      colorectal cancer.
AB  - While the management and prognosis of colorectal cancer are largely dependent on
      clinical features such as tumor stage, there is considerable variation in
      treatment and outcome not explained by traditional prognostic factors. To guide
      efforts by researchers and health-care providers to improve quality of care, we
      review studies of variation in treatment and outcome by patient and provider
      characteristics. Surgeon expertise and case volume are associated with improved
      tumor control, although surgeon and hospital factors are not associated
      consistently with perioperative mortality or long-term survival. Some studies
      indicate that patients are less likely to undergo permanent colostomy if they are
      treated by high-volume surgeons and hospitals. Differences in treatment and
      outcome of patients managed by health maintenance organizations or fee-for
      service providers have not generally been found. Older patients are less likely
      to receive adjuvant therapy after surgery, even after adjustment for comorbid
      illness. In the United States, black patients with colorectal cancer receive less
      aggressive therapy and are more likely to die of this disease than white
      patients, but cancer-specific survival differences are reduced or eliminated when
      black patients receive comparable treatment. Patients of low socioeconomic status
      (SES) have worse survival than those of higher SES, although the reasons for this
      discrepancy are not well understood. Variations in treatment may arise from
      inadequate physician knowledge of practice guidelines, treatment decisions based
      on unmeasured clinical factors, or patient preferences. To improve quality of
      care for colorectal cancer, a better understanding of mechanisms underlying
      associations between patient and provider characteristics and outcomes is
      required.

PMID- 11287445
TI  - Effects of retinoids on cancerous phenotype and apoptosis in organotypic cultures
      of ovarian carcinoma.
AB  - BACKGROUND: Retinoic acid analogues, called retinoids, have shown promise in
      clinical trials in preventing breast and ovarian cancers. Classic retinoids bind
      to retinoic acid receptors, which regulate cell growth. Some novel retinoids,
      such as fenretinide, i.e., N-(4-hydroxyphenyl)retinamide (4-HPR), induce
      apoptosis through retinoic acid receptor-independent mechanisms; however, they
      appear to do so only at concentrations above those achieved in clinical
      chemoprevention trials. At lower concentrations (< or =1 microM), 4-HPR acts like
      classic retinoids, by inducing differentiation through a receptor-dependent
      mechanism. Our goal was to compare the effects of novel receptor-independent
      (apoptotic) retinoids with those of classic growth-inhibitory retinoids at
      clinically achievable doses on growth, differentiation, and apoptosis in ovarian
      tissue. METHODS: Four receptor-independent (apoptotic) and seven growth
      inhibitory retinoids, including synthetic, low-toxicity compounds called
      heteroarotinoids, were administered at concentrations of 1 microM to organotypic
      cultures of ovarian primary and cancer cell lines: OVCAR-3, Caov-3, and SK-OV-3.
      After fixation, embedding, and sectioning, the growth fraction was quantified by
      measuring expression of the proliferation marker Ki-67/myb, differentiation was
      assessed by expression of mucin, and apoptosis was evaluated by the TUNEL assay.
      Spearman correlation analysis was performed on the data, and all P values were
      two-sided. RESULTS: All 11 retinoids reversed characteristics associated with the
      cancerous phenotype in all neoplastic cultures. Glandular structures were
      observed consistently in retinoid-treated, but not in untreated, OVCAR-3 and Caov
      3 cultures. All retinoids decreased growth fractions, and some increased mucin
      expression. All receptor-independent retinoids and two receptor-dependent
      retinoids induced apoptosis, and the induction correlated significantly with
      increased expression of the mucin MUC1 (r =.83; P =.03). Retinoids with ester
      linking groups did not induce apoptosis but decreased the growth fraction in
      correlation with MUC1 induction (r = -.93; P =.02). CONCLUSIONS: At clinically
      achievable concentrations, all retinoids tested decrease the growth fraction,
      induce differentiation and apoptosis. Induction of MUC1 expression is implicated
      in the mechanisms of action.

PMID- 11287446
TI  - Fruit, vegetables, dietary fiber, and risk of colorectal cancer.
AB  - BACKGROUND: Several recent large prospective cohort studies have failed to
      demonstrate the presumed protective effect of fruit, vegetable, and dietary fiber
      consumption on colorectal cancer risk. To further explore this issue, we have
      examined these associations in a population that consumes relatively low amounts
      of fruit and vegetables and high amounts of cereals. METHODS: We examined data
      obtained from a food-frequency questionnaire used in a population-based
      prospective mammography screening study of women in central Sweden. Women with
      colorectal cancer diagnosed through December 31, 1998, were identified by linkage
      to regional cancer registries. Cox proportional hazards models were used to
      estimate relative risks. All statistical tests were two-sided. RESULTS: During an
      average 9.6 years of follow-up of 61 463 women, we observed 460 incident cases of
      colorectal cancer (291 colon cancers, 159 rectal cancers, and 10 cancers at both
      sites). In the entire study population, total fruit and vegetable consumption was
      inversely associated with colorectal cancer risk. Subanalyses showed that this
      association was due largely to fruit consumption. The association was stronger,
      however, and the dose-response effect was more evident among individuals who
      consumed the lowest amounts of fruit and vegetables. Individuals who consumed
      less than 1.5 servings of fruit and vegetables per day had a relative risk for
      developing colorectal cancer of 1.65 (95% confidence interval = 1.23 to 2.20;
      P(trend) =.001) compared with individuals who consumed more than 2.5 servings. We
      observed no association between colorectal cancer risk and the consumption of
      cereal fiber, even at amounts substantially greater than previously examined, or
      of non-cereal fiber. CONCLUSIONS: Individuals who consume very low amounts of
      fruit and vegetables have the greatest risk of colorectal cancer. Relatively high
      consumption of cereal fiber does not appear to lower the risk of colorectal
      cancer.

PMID- 11287447
TI  - Methodology for treatment evaluation in patients with cancer metastatic to bone.
AB  - BACKGROUND: Patients with cancer metastatic to bone experience several adverse
      and clinically important skeletal-related events, including pathologic fractures,
      vertebral compressions with fracture, the need for surgery to treat or prevent
      fractures, and the need for radiation therapy for the treatment of bone pain. We
      present appropriate methods for describing and modeling the clinical course of
      skeletal-related events and comparing treatments for such events. METHODS: On the
      basis of data from a recently completed randomized, placebo-controlled trial
      involving 380 breast cancer patients with bone metastases, we tested the validity
      of the "events-per-person-years" method, one of the most commonly used
      techniques, for the analysis of skeletal-related events. We then used more robust
      methods of analysis that are based on fewer assumptions, including a random
      effects Poisson model, and contrasted the inferences about skeletal-related event
      rates and treatment effects for the different analytic methods. All statistical
      tests were two-sided. RESULTS: The events-per-person-years analysis
      underestimated substantially the variation in the data and is not appropriate to
      summarize the incidence rate of skeletal-related events. A random-effects Poisson
      model did provide a valid basis for analyzing such data. CONCLUSIONS: The
      underestimation of variability in data associated with the use of the events-per
      person-years analysis leads to unduly narrow confidence intervals for
      complication rates and inflated false-positive error rates in treatment
      comparisons. A random-effects Poisson model provides a valid, robust basis for
      describing the clinical course of bone complications and evaluating treatment
      effects.

PMID- 11287448
TI  - Gender- and smoking-related bladder cancer risk.
AB  - BACKGROUND: There is growing evidence that, when smoking habits are comparable,
      women incur a higher risk of lung cancer than men. Because smokers are also at
      risk for bladder cancer, we investigated possible sex differences in the
      susceptibility to bladder cancer among smokers. METHODS: A population-based, case
      -control study was conducted in Los Angeles, CA, involving 1514 case patients
      with bladder cancer and 1514 individually matched population control subjects.
      Information on tobacco use was collected through in-person interviews. Peripheral
      blood was collected from study participants to measure 3- and 4-aminobiphenyl
      (ABP)-hemoglobin adducts, a marker of arylamine exposure. Data were analyzed to
      determine whether the risk of bladder cancer differs between male and female
      smokers and whether female smokers exhibit higher levels of ABP-hemoglobin
      adducts than male smokers with comparable smoking habits. All statistical tests
      were two-sided. RESULTS: Cigarette smokers had a statistically significant 2.5
      fold higher risk (95% confidence interval = 2.1 to 3.0) of bladder cancer than
      never smokers. Use of filtered versus nonfiltered cigarettes, low-tar versus
      higher tar cigarettes, or the pattern of inhalation did not modify the risk. The
      risk of bladder cancer in women who smoked was statistically significantly higher
      than that in men who smoked comparable numbers of cigarettes (P =.016 for sex
      lifetime smoking interaction). Consistent with the sex difference in smoking
      related bladder cancer risk, the slopes of the linear regression lines of the 3-
      and 4-ABP--hemoglobin adducts by cigarettes per day were statistically
      significantly steeper in women than in men (P values for sex differences <.001
      and.006, respectively). CONCLUSION: The risk of bladder cancer may be higher in
      women than in men who smoked comparable amounts of cigarettes.

PMID- 11287449
TI  - Cancer risk in men exposed in utero to diethylstilbestrol.
AB  - BACKGROUND: An association between prenatal diethylstilbestrol (DES) exposure and
      cancer in men, especially testicular cancer, has been suspected, but findings
      from case-control studies have been inconsistent. This study was conducted to
      investigate the association between prenatal DES exposure and cancer risk in men
      via prospective follow-up. METHODS: A total of 3613 men whose prenatal DES
      exposure status was known were followed from 1978 through 1994. The overall and
      site-specific cancer incidence rates among the DES-exposed men were compared with
      those of the unexposed men in the study and with population-based rates. The
      relative rate (RR) was used to assess the strength of the association between
      prenatal DES exposure and cancer development. All statistical tests were two
      sided. RESULTS: Overall cancer rates among DES-exposed men were similar to those
      among unexposed men (RR = 1.07; 95% confidence interval [CI] = 0.58 to 1.96) and
      to national rates (RR = 0.99; 95% CI = 0.65 to 1.44). Testicular cancer may be
      elevated among DES-exposed men, since the RRs for testicular cancer were 3.05
      (95% CI = 0.65 to 22.0) times those of unexposed men in the study and 2.04 (95%
      CI = 0.82 to 4.20) times those of males in the population-based rates. The higher
      rate of testicular cancer in the DES-exposed men is, however, also compatible
      with a chance observation. CONCLUSIONS: To date, men exposed to DES in utero do
      not appear to have an increased risk of most cancers. It remains uncertain,
      however, whether prenatal DES exposure is associated with testicular cancer.

PMID- 11287450
TI  - Three-year results of the Finnish prostate cancer screening trial.

PMID- 11287451
TI  - Re: CYP17 promoter polymorphism and breast cancer in Australian women under age
      forty years.

PMID- 11287452
TI  - Re: Role of transforming growth factor-beta signaling in cancer.

PMID- 11287454
TI  - Re: Population-based, case-control study of HER2 genetic polymorphism and breast
      cancer risk.

PMID- 11287457
TI  - Re: Chemoprevention of gastric dysplasia: randomized trial of antioxidant
      supplements and anti-helicobacter pylori therapy.

PMID- 11287458
TI  - Epstein-Barr virus and breast cancer: search for antibodies to the novel BFRF1
      protein in sera of breast cancer patients.

PMID- 11287459
TI  - High-frequency stimulation produces a transient blockade of voltage-gated
      currents in subthalamic neurons.
AB  - The effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN)
      was analyzed with patch-clamp techniques (whole cell configuration, current- and
      voltage-clamp modes) in rat STN slices in vitro. A brief tetanus, consisting of
      100-micros bipolar stimuli at a frequency of 100--250 Hz during 1 min, produced a
      full blockade of ongoing STN activity whether it was in the tonic or bursting
      mode. This HFS-induced silence lasted around 6 min after the end of stimulation,
      was frequency dependent, could be repeated without alteration, and was not
      synaptically induced as it was still observed in the presence of blockers of
      ionotropic GABA and glutamate receptors or in the presence of cobalt at a
      concentration (2 mM) that blocks voltage-gated Ca(2+) channels and synaptic
      transmission. During HFS-induced silence, the following alterations were
      observed: the persistent Na(+) current (I(NaP)) was totally blocked (by 99%), the
      Ca(2+)-mediated responses were strongly reduced including the
      posthyperpolarization rebound (-62% in amplitude) and the plateau potential (-76%
      in duration), suggesting that T- and L-type Ca(2+) currents are transiently
      depressed by HFS, whereas the Cs(+)-sensitive, hyperpolarization-activated
      cationic current (I(h)) was little affected. Thus a high-frequency tetanus
      produces a blockade of the spontaneous activities of STN neurons as a result of a
      strong depression of intrinsic voltage-gated currents underlying single-spike and
      bursting modes of discharge. These effects of HFS, which are completely
      independent of synaptic transmission, provide a mechanism for interrupting
      ongoing activities of STN neurons.

PMID- 11287460
TI  - Spermine mediates inward rectification in potassium channels of turtle retinal
      Muller cells.
AB  - Retinal Muller cells are highly permeable to potassium as a consequence of their
      intrinsic membrane properties. Therefore these cells are able to play an
      important role in maintaining potassium homeostasis in the vertebrate retina
      during light-induced neuronal activity. Polyamines and other factors present in
      Muller cells have the potential to modulate the rectifying properties of
      potassium channels and alter the Muller cells capacity to siphon potassium from
      the extracellular space. In this study, the properties of potassium currents in
      turtle Muller cells were investigated using whole cell voltage-clamp recordings
      from isolated cells. Overall, the currents were inwardly rectifying.
      Depolarization elicited an outward current characterized by a fast transient that
      slowly recovered to a steady level along a double exponential time course. On
      hyperpolarization the evoked inward current was characterized by an instantaneous
      onset (or step) followed by a slowly developing sustained inward current. The
      kinetics of the time-dependent components (block of the transient outward current
      and slowly developing inward current) were dependent on holding potential and
      changes in the intracellular levels of magnesium ions and polyamines. In
      contrast, the instantaneous inward and the sustained outward currents were ohmic
      in character and remained relatively unaltered with changes in holding potential
      and concentration of applied spermine (0.5--2 mM). Our data suggest that cellular
      regulation in vivo of polyamine levels can differentially alter specific aspects
      of potassium siphoning by Muller cells in the turtle retina by modulating
      potassium channel function.

PMID- 11287461
TI  - Is persistent activity of calcium/calmodulin-dependent kinase required for the
      maintenance of LTP?
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is concentrated in the
      postsynaptic density (PSD) and plays an important role in the induction of long
      term potentiation (LTP). Because this kinase is persistently activated after the
      induction, its activity could also be important for LTP maintenance. Experimental
      tests of this hypothesis, however, have given conflicting results. In this paper
      we further explore the role of postsynaptic CaMKII in induction and maintenance
      of LTP. Postsynaptic application of a CaMKII inhibitor [autocamtide-3 derived
      peptide inhibitor (AC3-I), 2 mM] blocked LTP induction but had no detectable
      affect on N-methyl-D-aspartate (NMDA)-mediated synaptic transmission, indicating
      that the primary function of CaMKII in LTP is downstream from NMDA channel
      function. We next explored various methodological factors that could account for
      conflicting results on the effect of CaMKII inhibitors on LTP maintenance. In
      contrast to our previous work, we now carried out experiments at higher
      temperature (33 degrees C), used slices from adult animals, and induced LTP using
      a tetanic stimulation. However, we still found that LTP maintenance was not
      affected by postsynaptic application of AC3-I. Furthermore the inhibitor did not
      block LTP maintenance under conditions designed to enhance the Ca(2+)-dependent
      activity of protein phosphatases 1 and 2B (elevated Ca(2+), calmodulin, and an
      inhibitor of protein kinase A). We also tested the possibility that CaMKII
      inhibitor might not be able to affect CaMKII once it was inserted into the PSD.
      In whole-brain extracts, AC3-I blocked autophosphorylation of both soluble and
      particulate/PSD CaMKII with similar potencies although the potency of the
      inhibitor toward other CaMKII substrates varied. Thus we were unable to
      demonstrate a functional role of persistent Ca(2+)-independent CaMKII activity in
      LTP maintenance. Possible explanations of the data are discussed.

PMID- 11287462
TI  - Mechanism for increased hippocampal synaptic strength following differential
      experience.
AB  - Exposure to novel environments or behavioral training is associated with
      increased strength at hippocampal synapses. The present study employed quantal
      analysis techniques to examine the mechanism supporting changes in synaptic
      transmission that occur following differential behavioral experience. Measures of
      CA1 synaptic strength were obtained from hippocampal slices of rats exposed to
      novel environments or maintained in individual cages. The input/output (I/O)
      curve of extracellularly recorded population excitatory postsynaptic potentials
      (EPSPs) increased for animals exposed to enrichment. The amplitude of the
      synaptic response of the field potential was related to the fiber potential
      amplitude and the paired-pulse ratio, however, these measures were not altered by
      differential experience. Estimates of biophysical parameters of transmission were
      determined for intracellularly recorded unitary responses of CA1 pyramidal cells.
      Enrichment was associated with an increase in the mean unitary synaptic response,
      an increase in quantal size, and a trend for decreased input resistance and
      reduction in the stimulation threshold to elicit a unitary response. Paired-pulse
      facilitation, the percent of response failures, coefficient of variance, and
      estimates of quantal content were not altered by experience but correlated well
      with the mean unitary response amplitude. The results suggest that baseline
      synaptic strength is determined, to a large extent, by presynaptic release
      mechanisms. However, increased synaptic transmission following environmental
      enrichment is likely due to an increase in the number or efficacy of receptors at
      some synapses and the emergence of functional synaptic contacts between
      previously unconnected CA3 and CA1 cells.

PMID- 11287463
TI  - Distinct roles of CaMKII and PKA in regulation of firing patterns and K(+)
      currents in Drosophila neurons.
AB  - The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP-dependent
      protein kinase A (PKA) cascades have been implicated in neural mechanisms
      underlying learning and memory as supported by mutational analyses of the two
      enzymes in Drosophila. While there is mounting evidence for their roles in
      synaptic plasticity, less attention has been directed toward their regulation of
      neuronal membrane excitability and spike information coding. Here we report
      genetic and pharmacological analyses of the roles of PKA and CaMKII in the firing
      patterns and underlying K(+) currents in cultured Drosophila central neurons.
      Genetic perturbation of the catalytic subunit of PKA (DC0) did not alter the
      action potential duration but disrupted the frequency coding of spike-train
      responses to constant current injection in a subpopulation of neurons. In
      contrast, selective inhibition of CaMKII by the expression of an inhibitory
      peptide in ala transformants prolonged the spike duration but did not affect the
      spike frequency coding. Enhanced membrane excitability, indicated by spontaneous
      bursts of spikes, was observed in CaMKII-inhibited but not in PKA-diminished
      neurons. In wild-type neurons, the spike train firing patterns were highly
      reproducible under consistent stimulus conditions. However, disruption of either
      of these kinase pathways led to variable firing patterns in response to identical
      current stimuli delivered at a low frequency. Such variability in spike duration
      and frequency coding may impose problems for precision in signal processing in
      these protein kinase learning mutants. Pharmacological analyses of mutations that
      affect specific K(+) channel subunits demonstrated distinct effects of PKA and
      CaMKII in modulation of the kinetics and amplitude of different K(+) currents.
      The results suggest that PKA modulates Shaker A-type currents, whereas CaMKII
      modulates Shal-A type currents plus delayed rectifier Shab currents. Thus
      differential regulation of K(+) channels may influence the signal handling
      capability of neurons. This study provides support for the notion that, in
      addition to synaptic mechanisms, modulations in spike activity patterns may
      represent an important mechanism for learning and memory that should be explored
      more fully.

PMID- 11287464
TI  - Prefrontal cortex neurons reflecting reports of a visual illusion.
AB  - When a small, focally attended visual stimulus and a larger background frame
      shift location at the same time, the frame's new location can affect spatial
      perception. For horizontal displacements on the order of 1--2 degrees, when the
      frame moves more than the attended stimulus, human subjects may perceive that the
      attended stimulus has shifted to the right or left when it has not done so.
      However, that misapprehension does not disable accurate eye movements to the same
      stimulus. We trained a rhesus monkey to report the direction that an attended
      stimulus had shifted by making an eye movement to one of the two report targets.
      Then, using conditions that induce displacement illusions in human subjects, we
      tested the hypothesis that neuronal activity in the prefrontal cortex (PF) would
      reflect the displacement directions reported by the monkey, even when they
      conflicted with the actual displacement, if any, of the attended stimulus. We
      also predicted that these cells would have directional selectivity for movements
      used to make those reports, but not for similar eye movements made to fixate the
      attended stimulus. A population of PF neurons showed the predicted properties,
      which could not be accounted for on the basis of either eye-movement or frame
      shift parameters. This activity, termed report-related, began approximately 150
      ms before the onset of the reporting saccade. Another population of PF neurons
      showed greater directional selectivity for saccadic eye movements made to fixate
      the attended stimulus than for similar saccades made to report its displacement.
      In view of the evidence that PF functions to integrate inputs and actions
      occurring at different times and places, the present findings support the idea
      that such integration involves movements to acquire response targets, directly,
      as well as actions guided by less direct response rules, such as perceptual
      reports.

PMID- 11287465
TI  - Effects of spike parameters and neuromodulators on action potential waveform
      induced calcium entry into pyramidal neurons.
AB  - Neocortical pyramidal neurons express several different calcium channel types.
      Previous studies with square voltage steps have found modest biophysical
      differences between these calcium channel types as well as differences in their
      modulation by transmitters. We used acutely dissociated neocortical pyramidal
      neurons to test whether this diversity extends to different activation by
      physiological stimuli. We conclude that 1) peak amplitude, latency to peak, and
      the total charge entry for the Ca(2+) channel current is dependent on the shape
      of the mock action potential waveforms (APWs). 2) The percent contribution of the
      five high-voltage-activated currents to the whole cell current was not altered by
      using an APW as opposed to a voltage step to elicit the current. 3) The identity
      of the charge carrier affects the amplitude and decay of the whole cell current.
      With Ca(2+), there was a greater contribution of T-type current to the whole cell
      current. 4) Total Ba(2+) charge entry is linearly dependent on the number of
      spikes in the stimulating waveform and relatively insensitive to spike frequency.
      5) Current decay was greatest with Ca(2+) as the charge carrier and with minimal
      internal chelation. 6) Voltage-dependent neurotransmitter-mediated modulations
      can be reversed by multiple spikes. The extent of the reversal is dependent on
      the number of spikes in the stimulating waveform. Thus the neuronal activity
      pattern can determine the effectiveness of voltage-dependent and -independent
      modulatory pathways in neocortical pyramidal neurons.

PMID- 11287466
TI  - RCPH modulation of a multi-oscillator network: effects on the pyloric network of
      the spiny lobster.
AB  - The neuropeptide red pigment concentrating hormone (RPCH), which we have
      previously shown to activate the cardiac sac motor pattern and lead to a conjoint
      gastric mill-cardiac sac pattern in the spiny lobster Panulirus, also activates
      and modulates the pyloric pattern. Like the activity of gastric mill neurons in
      RPCH, the pattern of activity in the pyloric neurons is considerably more complex
      than that seen in control saline. This reflects the influence of the cardiac sac
      motor pattern, and particularly the upstream inferior ventricular (IV) neurons,
      on many of the pyloric neurons. RPCH intensifies this interaction by increasing
      the strength of the synaptic connections between the IV neurons and their targets
      in the stomatogastric ganglion. At the same time, RPCH enhances postinhibitory
      rebound in the lateral pyloric (LP) neuron. Taken together, these factors largely
      explain the complex pyloric pattern recorded in RPCH in Panulirus.

PMID- 11287467
TI  - Responses of neurons in neonatal cortex and thalamus to patterned visual
      stimulation through the naturally closed lids.
AB  - In studies of the developing mammalian visual system, it has been axiomatic that
      visual experience begins with eye-opening. Any role for neuronal activity earlier
      in development has been attributed to the patterned spontaneous activity found in
      retina and lateral geniculate nucleus (LGN). Here we show that, as early as 2 wk
      before eye-opening, visual stimuli presented through the closed eyelids can drive
      neuronal activity in LGN and striate cortex of the ferret. At this age,
      spontaneous activity in cortex is much lower than in LGN, and the visual
      responses of many cortical, but not geniculate, neurons depend on the orientation
      of a moving grating. Furthermore the selectivity of cortical neurons to the
      orientation of gratings presented through the closed eyelids improves with age.
      Thus neuronal activity patterned by visual experience, rather than by spontaneous
      retinal activity, is present in visual cortex much earlier than previously
      thought. This could have important implications for the self-organization of
      visual cortex.

PMID- 11287468
TI  - Model for olfactory discrimination and learning in Limax procerebrum
      incorporating oscillatory dynamics and wave propagation.
AB  - We extend our model of the procerebral (PC) lobe of Limax, which is comprised of
      a layer of coupled oscillators and a layer of memory neurons, each layer 4 rows
      by 20 columns, corresponding to the cell body layer (burster cells) and neuropil
      layer (nonburster cells) of the PC lobe. A gradient of connections in the layer
      of model burster cells induces periodic wave propagation, as measured in the PC
      lobe. We study odor representations in the biological PC lobe using the technique
      of Kimura and coworkers. Lucifer yellow injection into intact Limax after
      appetitive or aversive odor learning results in a band or patch of labeled cells
      in the PC lobe with the band long axis normal to the axis of wave propagation.
      Learning two odors yields two parallel bands of labeled PC cells. We introduce
      olfactory input to our model PC lobe such that each odor maximally activates a
      unique row of four cells which produces a short-term memory trace of odor
      stimulation. A winner-take-all synaptic competition enabled by collapse of the
      phase gradient during odor presentation produces a single short-term memory band
      for each odor. The short-term memory is converted to long-term memory if odor
      stimulation is followed by activation of an input pathway for the unconditioned
      stimulus (US) which presumably results in release of one or more neuromodulatory
      amines or peptides in the PC lobe.

PMID- 11287469
TI  - Characterization of outward currents induced by 5-HT in neurons of rat
      dorsolateral septal nucleus.
AB  - Properties of the 5-hydroxytryptamine (5-HT)-induced current (I(5-HT)) were
      examined in neurons of rat dorsolateral septal nucleus (DLSN) by using whole cell
      patch-clamp techniques. I(5-HT) was associated with an increase in the membrane
      conductance of DLSN neurons. The reversal potential of I(5-HT) was -93 +/- 6 (SE)
      mV (n = 7) in the artificial cerebrospinal fluid (ACSF) and was changed by 54 mV
      per decade change in the external K(+) concentration, indicating that I(5-HT) is
      carried exclusively by K(+). Voltage dependency of the K(+) conductance
      underlying I(5-HT) was investigated by using current-voltage relationship. I(5
      HT) showed a linear I-V relation in 63%, inward rectification in 21%, and outward
      rectification in 16% of DLSN neurons. (+/-)-8-Hydroxy-dipropylaminotetralin
      hydrobromide (30 microM), a selective 5-HT(1A) receptor agonist, also produced
      outward currents with three types of voltage dependency. Ba(2+) (100 microM)
      blocked the inward rectifier I(5-HT) but not the outward rectifier I(5-HT). In
      I(5-HT) with linear I-V relation, blockade of the inward rectifier K(+) current
      by Ba(2+) (100 microM) unmasked the outward rectifier current in DLSN neurons.
      These results suggest that I(5-HT) with linear I-V relation is the sum of inward
      rectifier and outward rectifier K(+) currents in DLSN neurons. Intracellular
      application of guanosine-5'-O-(3-thiotriphosphate) (300 microM) and guanosine-5'
      O-(2-thiodiphosphate) (5 mM), blockers of G protein, irreversibly depressed I(5
      HT). Protein kinase C (PKC) 19-36 (20 microM), a specific PKC inhibitor,
      depressed the outward rectifier I(5-HT) but not the inward rectifier I(5-HT). I(5
      HT) was depressed by N-ethylmaleimide, which uncouples the G-protein-coupled
      receptor from pertussis-toxin-sensitive G proteins. H-89 (10 microM) and
      adenosine 3',5'-cyclic monophosphothioate Rp-isomer (300 microM), protein kinase
      A inhibitors, did not depress I(5-HT). Phorbol 12-myristate 13-acetate (10
      microM), an activator of PKC, produced an outward rectifying K(+) current. These
      results suggest that both 5-HT-induced inward and outward rectifying currents are
      mediated by a G protein and that PKC is probably involved in the transduction
      pathway of the outward rectifying I(5-HT) in DLSN neurons.

PMID- 11287470
TI  - Role of primate magnocellular red nucleus neurons in controlling hand preshaping
      during reaching to grasp.
AB  - Reaching to grasp is of fundamental importance to primate motor behavior and
      requires coordinating hand preshaping with limb transport and grasping. We aimed
      to clarify the role of cerebellar output via the magnocellular red nucleus (RNm)
      to the control of reaching to grasp. Rubrospinal fibers originating from RNm
      constitute one pathway by which cerebellar output influences spinal circuitry
      directly. We recorded discharge from individual forelimb RNm neurons while
      monkeys performed a reach-to-grasp task and two tasks that were similar to the
      reach-to-grasp task in trajectory, amplitude, and direction but did not include a
      grasp. One of these, the device task, elicited reaches while holding a handle,
      and the other, the free-reach task, elicited reaches that did not require any
      specific hand use for task performance. The results demonstrate that coordinated
      whole-limb reaching movements are associated with large discharge modulations of
      RNm neurons predominantly when hand use is included. Therefore RNm neurons can at
      best only make a minor contribution to the control of reaching movements that
      lack hand use. We evaluated relations between the discharge of individual RNm
      neurons and electromyographic (EMG) activity of forelimb muscles during the reach
      to-grasp task by comparing times of peak RNm discharge to times of peak EMG
      activity. The results are consistent with the view that RNm discharge may
      contribute to EMG activity of both distal and proximal muscles during reaching to
      grasp especially digit extensor and limb elevation muscles. Relations between the
      discharge of individual RNm neurons and movements of the metacarpi-phalangeal
      (MCP), wrist, elbow, and shoulder joints during individual trials of task
      performance were quantified by parametric correlation analyses on a subset of
      neurons studied during the reach-to-grasp and free-reach tasks. The results
      indicate that MCP extensions were consistently preceded by bursts of RNm
      discharge, and strong correlations were observed between parameters of discharge
      and the duration, velocity, and amplitude of corresponding MCP extensions. In
      contrast, relations between discharge and movements of proximal joints were
      poorly represented, and RNm discharge was not related to the speed of limb
      transport. Based on our data and those of others, we hypothesize that cerebellar
      output via RNm is specialized for controlling hand use and conclude that RNm may
      contribute to the control of hand preshaping during reaching to grasp by
      activating muscle synergies that produce the appropriate MCP extension at the
      appropriate phase of limb transport.

PMID- 11287471
TI  - Neurotensin excites periaqueductal gray neurons projecting to the rostral
      ventromedial medulla.
AB  - Microinjection of neurotensin into the midbrain periaqueductal gray (PAG)
      produces a potent and naloxone-insensitive analgesic effect. To test the
      hypothesis that neurotensin induces the analgesic effect by activating the PAG
      rostral ventromedial medulla (RVM) descending antinociceptive pathway, PAG
      neurons that project to RVM (PAG-RVM) were identified by microinjecting DiI(C18),
      a retrograde tracing dye, into the rat RVM. Subsequently, fluorescently labeled
      PAG-RVM projection neurons were acutely dissociated and selected for whole cell
      patch-clamp recordings. During current-clamp recordings, neurotensin depolarized
      retrogradely labeled PAG-RVM neurons and evoked action potentials. Voltage-clamp
      recordings indicated that neurotensin excited PAG-RVM neurons by opening the
      voltage-insensitive and nonselective cation channels. Both SR 48692, a selective
      NTR-1 antagonist, and SR 142948A, a nonselective antagonist of NTR-1 and NTR-2,
      failed to prevent neurotensin from exciting PAG-RVM neurons. Neurotensin failed
      to evoke cationic currents after internally perfusing PAG-RVM projection neurons
      with GDP-beta-S or anti-G(alpha q/11) antiserum. Cellular Ca(2+) fluorescence
      measurement using fura-2 indicated that neurotensin rapidly induced Ca(2+)
      release from intracellular stores of PAG-RVM neurons. Neurotensin-evoked cationic
      currents were blocked by heparin, an IP(3) receptor antagonist, and 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a fast chelator of
      Ca(2+). These results suggest that by activating a novel subtype of neurotensin
      receptors, neurotensin depolarizes and excites PAG-RVM projection neurons through
      enhancing Ca(2+)-dependent nonselective cationic conductance. The coupling
      mechanism via G(alpha q/11) proteins is likely to involve the production of
      IP(3), and subsequent IP(3)-evoked Ca(2+) release leads to the opening of
      nonselective cation channels.

PMID- 11287472
TI  - High-pass filtering of corticothalamic activity by neuromodulators released in
      the thalamus during arousal: in vitro and in vivo.
AB  - The thalamus is the principal relay station of sensory information to the
      neocortex. In return, the neocortex sends a massive feedback projection back to
      the thalamus. The thalamus also receives neuromodulatory inputs from the brain
      stem reticular formation, which is vigorously activated during arousal. We
      investigated the effects of two neuromodulators, acetylcholine and
      norepinephrine, on corticothalamic responses in vitro and in vivo. Results from
      rodent slices in vitro showed that acetylcholine and norepinephrine depress the
      efficacy of corticothalamic synapses while enhancing their frequency-dependent
      facilitation. This produces a stronger depression of low-frequency responses than
      of high-frequency responses. The effects of acetylcholine and norepinephrine were
      mimicked by muscarinic and alpha(2)-adrenergic receptor agonists and blocked by
      muscarinic and alpha-adrenergic antagonists, respectively. Stimulation of the
      brain stem reticular formation in vivo also strongly depressed corticothalamic
      responses. The suppression was very strong for low-frequency responses, which do
      not produce synaptic facilitation, but absent for high-frequency corticothalamic
      responses. As in vitro, application of muscarinic and alpha-adrenergic
      antagonists into the thalamus in vivo abolished the suppression of
      corticothalamic responses induced by stimulating the reticular formation. In
      conclusion, cholinergic and noradrenergic activation during arousal high-pass
      filters corticothalamic activity. Thus, during arousal only high-frequency inputs
      from the neocortex are allowed to reach the thalamus. Neuromodulators acting on
      corticothalamic synapses gate the flow of cortical activity to the thalamus as
      dictated by behavioral state.

PMID- 11287473
TI  - Hippocampal synaptic transmission and plasticity are preserved in myosin Va
      mutant mice.
AB  - Recent studies have identified myosin Va as an organelle motor that may have
      important functions in neurons. Abundantly expressed at the hippocampal
      postsynaptic density, it interacts with protein complexes involved in synaptic
      plasticity. It is also located in presynaptic terminals and may function to
      recruit vesicles in the reserve pool to the active zone. Dilute-lethal mice are
      spontaneous myosin Va mutants and have severe neurological symptoms. We studied
      hippocampal physiology at CA3-CA1 excitatory synapses in dilute-lethal mutant
      mice to test the hypothesis that myosin Va plays a role in pre- or postsynaptic
      elements of synaptic transmission. In all assays performed, the mutant synapses
      appeared to be functioning normally, both pre- and postsynaptically. These data
      suggest that myosin Va is not essential for the synaptic release machinery,
      postsynaptic receptor composition, or plasticity at this synapse, but does not
      exclude significant roles for myosin Va in other cell types nor potential
      compensation by other myosin V isoforms.

PMID- 11287474
TI  - Depression of windup of spinal neurons in the neonatal rat spinal cord in vitro
      by an NK3 tachykinin receptor antagonist.
AB  - The effects of the NK3 tachykinin receptor antagonist SR 142801 on synaptic
      transmission and spike windup induced by trains of stimuli applied to a dorsal
      root were investigated with intra- and extracellular recording from the neonatal
      rat spinal cord in vitro. SR 142801 (10 microM) reduced the depolarization
      (recorded from lumbar ventral roots) induced by senktide (an NK3 agonist) more
      strongly than the one evoked by substance P methyl ester (SPMeO; an NK1 agonist).
      Nevertheless, after a long (>2 h) application time, SR 142801 largely depressed
      the response to SPMeO as well. When NK1 or NK3 receptors were blocked by >50% in
      the presence of SR 142801, there was also a significant reduction in the
      cumulative depolarization induced by repeated stimuli to a single dorsal root.
      This blocking action by SR 142801 was also observed in the presence of the N
      methyl-D-aspartate (NMDA) receptor antagonist D-aminophosphonovalerate (APV) and
      the calcium channel blocker nifedipine. Intracellular data from lumbar
      motoneurons showed that the spike windup was the first and most sensitive target
      for the SR 142801 blocking effect. Increasing stimulus strength to dorsal root
      fibers could partly surmount such a block. SR 142801 per se had no direct action
      on fast synaptic transmission, membrane potential, or input resistance. These
      findings indicate that SR 142801 could lead to an early, large reduction in the
      windup of action potential discharge by motoneurons, suggesting its ability to
      suppress the reflex component of central sensitization evoked by repeated dorsal
      root stimuli.

PMID- 11287475
TI  - Pretectal neurons optimized for the detection of saccade-like movements of the
      visual image.
AB  - The visual response properties of nondirectional wide-field sensitive neurons in
      the wallaby pretectum are described. These neurons are called scintillation
      detectors (SD-neurons) because they respond vigorously to rapid, high contrast
      visual changes in any part of their receptive fields. SD-neurons are most densely
      located within a 1- to 2-mm radius from the nucleus of the optic tract,
      interspersed with direction-selective retinal slip cells. Receptive fields are
      monocular and cover large areas of the contralateral visual field (30--120
      degrees ). Response sizes are equal for motion in all directions, and spontaneous
      activities are similar for all orientations of static sine-wave gratings.
      Response magnitude increases near linearly with increasing stimulus diameter and
      contrast. The mean response latency for wide-field, high-contrast motion
      stimulation was 43.4 +/- 9.4 ms (mean +/- SD, n = 28). The optimum visual stimuli
      for SD-neurons are wide-field, low spatial frequency (<0.2 cpd) scenes moving at
      high velocities (75--500 degrees /s). These properties match the visual input
      during saccades, indicating optimal sensitivity to rapid eye movements. Cells
      respond to brightness increments and decrements, suggesting inputs from ON and
      OFF channels. Stimulation with high-speed, low spatial frequency gratings
      produces oscillatory responses at the input temporal frequency. Conversely, high
      spatial frequency gratings give oscillations predominantly at the second harmonic
      of the temporal frequency. Contrast reversing sine-wave gratings elicit
      transient, phase-independent responses. These responses match the properties of Y
      retinal ganglion cells, suggesting that they provide inputs to SD-neurons. We
      discuss the possible role of SD-neurons in suppressing ocular following during
      saccades and in the blink or saccade-locked modulation of lateral geniculate
      nucleus activity to control retino-cortical information flow.

PMID- 11287476
TI  - Responses and afferent pathways of superficial and deeper c(1)-c(2) spinal cells
      to intrapericardial algogenic chemicals in rats.
AB  - Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent
      fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to
      compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2)
      spinal neurons to noxious chemical stimulation of cardiac afferents and determine
      the relative contribution of vagal and sympathetic afferent pathways for
      transmission of noxious cardiac afferent input to C(1)--C(2) neurons.
      Extracellular potentials of single C(1)--C(2) neurons were recorded in
      pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the
      pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that
      contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and
      prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the
      activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae,
      whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P <
      0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41
      (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial
      chemicals. E or I neurons responsive to intrapericardial chemicals were
      subdivided into two groups: short-lasting (SL) and long-lasting (LL) response
      patterns. In superficial gray matter, excitatory responses to cardiac inputs were
      more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic
      field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2)
      spinal neurons that responded to intrapericardial chemicals; 31 neurons were
      classified as wide dynamic range, 49 were high threshold, 5 responded only to
      joint movement, and no neuron was classified as low threshold. For superficial
      neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast,
      31% of the deeper neurons had small somatic fields and 46% had bilateral fields.
      Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2
      I) neurons; sequential transection of the contralateral cervical vagus nerve
      (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in
      4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt
      effects of sympathetic afferent input abolished responses to cardiac input in
      10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results
      of this study support the concept that C(1)-C(2) superficial and deeper spinal
      neurons play a role in integrating cardiac noxious inputs that travel in both the
      cervical vagal and/or thoracic sympathetic afferent nerves.

PMID- 11287477
TI  - GABA uptake and heterotransport are impaired in the dentate gyrus of epileptic
      rats and humans with temporal lobe sclerosis.
AB  - In vivo dialysis and in vitro electrophysiological studies suggest that GABA
      uptake is altered in the dentate gyrus of human temporal lobe epileptics
      characterized with mesial temporal sclerosis (MTLE). Concordantly, anatomical
      studies have shown that the pattern of GABA-transporter immunoreactivity is also
      altered in this region. This decrease in GABA uptake, presumably due to a change
      in the GABA transporter system, may help preserve inhibitory tone interictally.
      However, transporter reversal can also occur under several conditions, including
      elevations in [K(+)]o, which occurs during seizures. Thus GABA transporters could
      contribute to seizure termination and propagation through heterotransport. To
      test whether GABA transport is compromised in both the forward (uptake) and
      reverse (heterotransport) direction in the sclerotic epileptic dentate gyrus, the
      physiological effects of microapplied GABA and nipecotic acid (NPA; a compound
      that induces heterotransport) were examined in granule cells in hippocampal
      slices from kainate (KA)-induced epileptic rats and patients with temporal lobe
      epilepsy (TLE). GABA- and NPA-induced responses were prolonged in granule cells
      from epileptic rats versus controls (51.3 and 31.3% increase, respectively) while
      the conductance change evoked with NPA microapplication was reduced by 40%.
      Furthermore the ratio of GABA/NPA conductance, but not duration, was
      significantly >1 in epileptic rats but not controls, suggesting a compromise in
      transporter function in both directions. Similar changes were observed in tissue
      resected from epileptic patients with medial temporal sclerosis but not in those
      without the anatomical changes associated with MTLE. These data suggest that the
      GABA transporter system is functionally compromised in both the forward and
      reverse directions in the dentate gyrus of chronically epileptic tissue
      characterized by mesial temporal sclerosis. This alteration may enhance
      inhibitory tone interically yet be permissive for seizure propagation due to a
      decreased probability for GABA heterotransport during seizures.

PMID- 11287478
TI  - Gap junctions and inhibitory synapses modulate inspiratory motoneuron
      synchronization.
AB  - Interneuronal electrical coupling via gap junctions and chemical synaptic
      inhibitory transmission are known to have roles in the generation and
      synchronization of activity in neuronal networks. Uncertainty exists regarding
      the roles of these two modes of interneuronal communication in the central
      respiratory rhythm-generating system. To assess their roles, we performed studies
      on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord
      preparations where rhythmic inspiratory motor activity can readily be recorded
      from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity
      observed had two temporal characteristics: the basic respiratory frequency
      occurring on a long time scale and the synchronous neuronal discharge within the
      inspiratory burst occurring on a short time scale. In both preparations, we
      observed that bath application of gap-junction blockers, including 18 alpha
      glycyrrhetinic acid, 18 beta-glycyrrhetinic acid, and carbenoxolone, all caused a
      reduction in respiratory frequency. In contrast, peak integrated phrenic and
      hypoglossal inspiratory activity was not significantly changed by gap-junction
      blockade. On a short-time-scale, gap-junction blockade increased the degree of
      synchronization within an inspiratory burst observed in both nerves. In contrast,
      opposite results were observed with blockade of GABA(A) and glycine receptors. We
      found that respiratory frequency increased with receptor blockade, and
      simultaneous blockade of both receptors consistently resulted in a reduction in
      short-time-scale synchronized activity observed in phrenic and hypoglossal
      inspiratory bursts. These results support the concept that the central
      respiratory system has two components: a rhythm generator responsible for the
      production of respiratory cycle timing and an inspiratory pattern generator that
      is involved in short-time-scale synchronization. In the neonatal rodent,
      properties of both components can be regulated by interneuronal communication via
      gap junctions and inhibitory synaptic transmission.

PMID- 11287479
TI  - Mouse taste cells with glialike membrane properties.
AB  - Taste buds are sensory structures made up by tightly packed, specialized
      epithelial cells called taste cells. Taste cells are functionally heterogeneous,
      and a large proportion of them fire action potentials during chemotransduction.
      In view of the narrow intercellular spaces within the taste bud, it is expected
      that the ionic composition of the extracellular fluid surrounding taste cells may
      be altered significantly by activity. This consideration has led to postulate the
      existence of glialike cells that could control the microenvironment in taste
      buds. However, the functional identification of such cells has been so far
      elusive. By using the patch-clamp technique in voltage-clamp conditions, I
      identified a new type of cells in the taste buds of the mouse vallate papilla.
      These cells represented about 30% of cells patched in taste buds and were
      characterized by a large leakage current. Accordingly, I named them "Leaky"
      cells. The leakage current was carried by K(+), and was blocked by Ba(2+) but not
      by tetraethylammonium (TEA). Other taste cells, such as those possessing voltage
      gated Na(+) currents and thought to be chemosensory in function, did not express
      any sizeable leakage current. Consistent with the presence of a leakage
      conductance, Leaky cells had a low input resistance (approximately 0.25 G Omega).
      In addition, their zero-current ("resting") potential was close to the
      equilibrium potential for potassium ions. The electrophysiological analysis of
      the membrane currents remaining after pharmacological block by Ba(2+) revealed
      that Leaky cells also possessed a Cl(-) conductance. However, in resting
      conditions the membrane of these cells was about 60 times more permeable to K(+)
      than to Cl(-). The resting potassium conductance in Leaky cells could be involved
      in dissipating rapidly the increase in extracellular K(+) during action potential
      discharge in chemosensory cells. Thus Leaky cells might represent glialike
      elements in taste buds. These findings support a model in which specific cells
      control the chemical composition of intercellular fluid in taste buds.

PMID- 11287480
TI  - Response properties of mechanoreceptors and nociceptors in mouse glabrous skin:
      an in vivo study.
AB  - The increasing use of transgenic mice for the study of pain mechanisms
      necessitates comprehensive understanding of the murine somatosensory system.
      Using an in vivo mouse preparation, we studied response properties of tibial
      nerve afferent fibers innervating glabrous skin. Recordings were obtained from
      225 fibers identified by mechanical stimulation of the skin. Of these, 106 were
      classed as A beta mechanoreceptors, 51 as A delta fibers, and 68 as C fibers. A
      beta mechanoreceptors had a mean conduction velocity of 22.2 +/- 0.7 (SE) m/s
      (13.8--40.0 m/s) and a median mechanical threshold of 2.1 mN (0.4--56.6 mN) and
      were subclassed as rapidly adapting (RA, n = 75) or slowly adapting (SA, n = 31)
      based on responses to constant force mechanical stimuli. Conduction velocities
      ranged from 1.4 to 13.6 m/s (mean 7.1 +/- 0.6 m/s) for A delta fibers and 0.21 to
      1.3 m/s (0.7 +/- 0.1 m/s) for C fibers. Median mechanical thresholds were 10.4
      and 24.4 mN for A delta and C fibers, respectively. Responses of A delta and C
      fibers evoked by heat (35--51 degrees C) and by cold (28 to -12 degrees C)
      stimuli were determined. Mean response thresholds of A delta fibers were 42.0 +/-
      3.1 degrees C for heat and 7.6 +/- 3.8 degrees C for cold, whereas mean response
      thresholds of C fibers were 40.3 +/- 0.4 degrees C for heat and 10.1 +/- 1.9
      degrees C for cold. Responses evoked by heat and cold stimuli increased
      monotonically with stimulus intensity. Although only 12% of tested A delta fibers
      were heat sensitive, 50% responded to cold. Only one A delta nociceptor responded
      to both heat and cold stimuli. In addition, 40% of A delta fibers were only
      mechanosensitive since they responded neither to heat nor to cold stimuli.
      Thermal stimuli evoked responses from the majority of C fibers: 82% were heat
      sensitive, while 77% of C fibers were excited by cold, and 68% were excited by
      both heat and cold stimuli. Only 11% of C fibers were insensitive to heat and/or
      cold. This in vivo study provides an analysis of mouse primary afferent fibers
      innervating glabrous skin including new information on encoding of noxious
      thermal stimuli within the peripheral somatosensory system of the mouse. These
      results will be useful for future comparative studies with transgenic mice.

PMID- 11287481
TI  - Adaptive adjustment of connectivity in the inferior colliculus revealed by focal
      pharmacological inactivation.
AB  - In the midbrain sound localization pathway of the barn owl, a map of auditory
      space is synthesized in the external nucleus of the inferior colliculus (ICX) and
      transmitted to the optic tectum. Early auditory experience shapes these maps of
      auditory space in part by modifying the tuning of the constituent neurons for
      interaural time difference (ITD), a primary cue for sound-source azimuth. Here we
      show that these adaptive modifications in ITD tuning correspond to changes in the
      pattern of connectivity within the inferior colliculus. We raised owls with an
      acoustic filtering device in one ear that caused frequency-dependent changes in
      sound timing and level. As reported previously, device rearing shifted the
      representation of ITD in the ICX and tectum but not in the primary source of
      input to the ICX, the central nucleus of the inferior colliculus (ICC). We
      applied the local anesthetic lidocaine (QX-314) iontophoretically in the ICC to
      inactivate small populations of neurons that represented particular values of
      frequency and ITD. We measured the effect of this inactivation in the optic tecta
      of a normal owl and owls raised with the device. In the normal owl, inactivation
      at a critical site in the ICC eliminated responses in the tectum to the frequency
      specific ITD value represented at the site of inactivation in the ICC. The
      location of this site was consistent with the known pattern of ICC-ICX-tectum
      connectivity. In the device-reared owls, adaptive changes in the representation
      of ITD in the tectum corresponded to dramatic and predictable changes in the
      locations of the critical sites of inactivation in the ICC. Given that the
      abnormal representation of ITD in the tectum depended on frequency and was likely
      conveyed directly from the ICX, these results suggest that experience causes
      large-scale, frequency-specific adjustments in the pattern of connectivity
      between the ICC and the ICX.

PMID- 11287482
TI  - Selective stimulation of cat sciatic nerve using an array of varying-length
      microelectrodes.
AB  - Restoration of motor function to individuals who have had spinal cord injuries or
      stroke has been hampered by the lack of an interface to the peripheral nervous
      system. A suitable interface should provide selective stimulation of a large
      number of individual muscle groups with graded recruitment of force. We have
      developed a new neural interface, the Utah Slanted Electrode Array (USEA), that
      was designed to be implanted into peripheral nerves. Its goal is to provide such
      an interface that could be useful in rehabilitation as well as neuroscience
      applications. In this study, the stimulation capabilities of the USEA were
      evaluated in acute experiments in cat sciatic nerve. The recruitment properties
      and the selectivity of stimulation were examined by determining the target
      muscles excited by stimulation via each of the 100 electrodes in the array and
      using force transducers to record the force produced in these muscles. It is
      shown in the results that groups of up to 15 electrodes were inserted into
      individual fascicles. Stimulation slightly above threshold was selective to one
      muscle group for most individual electrodes. At higher currents, co-activation of
      agonist but not antagonist muscles was observed in some instances. Recruitment
      curves for the electrode array were broader with twitch thresholds starting at
      much lower currents than for cuff electrodes. In these experiments, it is also
      shown that certain combinations of electrode pairs, inserted into an individual
      fascicle, excite fiber populations with substantial overlap, whereas other pairs
      appear to address independent populations. We conclude that the USEA permits more
      selective stimulation at much lower current intensities with more graded
      recruitment of individual muscles than is achieved by conventional cuff
      electrodes.

PMID- 11287483
TI  - Inactivation of voltage-activated Na(+) currents contributes to different
      adaptation properties of paired mechanosensory neurons.
AB  - Voltage-activated sodium current (I(Na)) is primarily responsible for the leading
      edge of the action potential in many neurons. While I(Na) generally activates
      rapidly when a neuron is depolarized, its inactivation properties differ
      significantly between different neurons and even within one neuron, where I(Na)
      often has slowly and rapidly inactivating components. I(Na) inactivation has been
      suggested to regulate action potential firing frequency in some cells, but no
      clear picture of this relationship has emerged. We studied I(Na) in both members
      of the paired mechanosensory neurons of a spider slit-sense organ, where one
      neuron adapts rapidly (type A) and the other slowly (type B) in response to a
      step depolarization. In both neuron types I(Na) activated and inactivated with
      single time constants of 2--3 ms and 5--10 ms, respectively, varying with the
      stimulus intensity. However, there was a clear difference in the steady-state
      inactivation properties of the two neuron types, with the half-maximal
      inactivation (V(50)) being -40.1 mV in type A neurons and -58.1 mV in type B
      neurons. Therefore I(Na) inactivated closer to the resting potential in the more
      slowly adapting neurons. I(Na) also recovered from inactivation significantly
      faster in type B than type A neurons, and the recovery was dependent on
      conditioning voltage. These results suggest that while the rate of I(Na)
      inactivation is not responsible for the difference in the adaptation behavior of
      these two neuron types, the rate of recovery from inactivation may play a major
      role. Inactivation at lower potentials could therefore be crucial for more rapid
      recovery.

PMID- 11287484
TI  - Synaptically activated calcium responses in dendrites of hippocampal oriens
      alveus interneurons.
AB  - Activation of metabotropic glutamate receptors (mGluRs) by agonists increases
      intracellular calcium levels ([Ca(2+)](i)) in interneurons of stratum
      oriens/alveus (OA) of the hippocampus. We examined the mechanisms that contribute
      to dendritic Ca(2+) increases in these interneurons during agonist activation of
      mGluRs and during synaptically evoked burst discharges, using simultaneous whole
      cell recordings and confocal Ca(2+) imaging in rat hippocampal slices. First, we
      found that the group I/II mGluR agonist 1S,3R-1-aminocyclopentane-1,3
      dicarboxylic acid (ACPD; 100 microM) increased dendritic [Ca(2+)](i) and
      depolarized OA interneurons. Dendritic Ca(2+) responses were correlated with
      membrane depolarizations, but Ca(2+) responses induced by ACPD were larger in
      amplitude than those elicited by equivalent somatic depolarization. Next, we used
      linescans to measure changes in dendritic [Ca(2+)](i) during synaptically evoked
      burst discharges and somatically elicited repetitive firing in disinhibited
      slices. Dendritic Ca(2+) signals and electrophysiological responses were stable
      over repeated trials. Peak Ca(2+) responses were linearly related to number and
      frequency of action potentials in burst discharges for both synaptic and somatic
      stimulation, but the slope of the relationship was steeper for responses evoked
      somatically. Synaptically evoked [Ca(2+)](i) rises and excitatory postsynaptic
      potentials were abolished by antagonists of ionotropic glutamate receptors. The
      group I/II mGluR antagonist S-alpha-methyl-4-carboxyphenylglycine (500 microM)
      produced a significant partial reduction of synaptically evoked dendritic Ca(2+)
      responses. The mGluR antagonist did not affect synaptically evoked burst
      discharges and did not reduce either Ca(2+) responses or burst discharges evoked
      somatically. Therefore ionotropic glutamate receptors appear necessary for
      synaptically evoked dendritic Ca(2+) responses, and group I/II mGluRs may
      contribute partially to these responses. Dendritic [Ca(2+)](i) rises mediated by
      both ionotropic and metabotropic glutamate receptors may be important for
      synaptic plasticity and the selective vulnerability to excitotoxicity of OA
      interneurons.

PMID- 11287485
TI  - Long-term correlations in the spike trains of medullary sympathetic neurons.
AB  - Fano factor analysis was used to characterize the spike trains of single
      medullary neurons with sympathetic nerve-related activity in cats that were
      decerebrate or anesthetized with Dial-urethan or urethan. For this purpose,
      values (Fano factor) of the variance of the number of extracellularly recorded
      spikes divided by the mean number of spikes were calculated for window sizes of
      systematically varied length. For window sizes < or =10 ms, the Fano factor was
      close to one, as expected for a Bernoulli process with a low probability of
      success. The Fano factor dipped below one as the window size approached the
      shortest interspike interval (ISI) and reached its nadir at window sizes near the
      modal ISI. The extent of the dip reflected the shape (skewness) of the ISI
      histogram with the dip being smallest for the most asymmetric distributions. Most
      importantly, for a wide range of window sizes exceeding the modal ISI, the Fano
      factor curve took the form of a power law function. This was the case independent
      of the component (cardiac related, 10 Hz, or 2--6 Hz) of inferior cardiac
      sympathetic nerve discharge to which unit activity was correlated or the
      medullary region (lateral tegmental field, raphe, caudal and rostral
      ventrolateral medulla) in which the neuron was located. The power law
      relationship in the Fano factor curves was eliminated by randomly shuffling the
      ISIs even though the distribution of the intervals was unchanged. Thus the power
      law relationship arose from long-term correlations among ISIs that were disrupted
      by shuffling the data. The presence of long-term correlations across different
      time scales reflects the property of statistical self-similarity that is
      characteristic of fractal processes. In most cases, we found that mean ISI and
      variance for individual spike trains increased as a function of the number of
      intervals counted. This can be attributed to the clustering of long and short
      ISIs, which also is an inherent property of fractal time series. We conclude that
      the spike trains of brain stem sympathetic neurons have fractal properties.

PMID- 11287486
TI  - Nonlinear behavior of sinusoidally forced pyloric pacemaker neurons.
AB  - Periodic current forcing was used to investigate the intrinsic dynamics of a
      small group of electrically coupled neurons in the pyloric central pattern
      generator (CPG) of the lobster. This group contains three neurons, namely the two
      pyloric dilator (PD) motoneurons and the anterior burster (AB) interneuron.
      Intracellular current injection, using sinusoidal waveforms of varying amplitude
      and frequency, was applied in three configurations of the pacemaker neurons: 1)
      the complete pacemaker group, 2) the two PDs without the AB, and 3) the AB neuron
      isolated from the PDs. Depending on the frequency and amplitude of the injected
      current, the intact pacemaker group exhibited a wide variety of nonlinear
      behaviors, including synchronization to the forcing, quasiperiodicity, and
      complex dynamics. In contrast, a single, broad 1:1 entrainment zone characterized
      the response of the PD neurons when isolated from the main pacemaker neuron AB.
      The isolated AB responded to periodic forcing in a manner similar to the complete
      pacemaker group, but with wider zones of synchronization. We have built an analog
      electronic circuit as an implementation of a modified Hindmarsh-Rose model for
      simulating the membrane potential activity of pyloric neurons. We subjected this
      electronic model neuron to the same periodic forcing as used in the biological
      experiments. This four-dimensional electronic model neuron reproduced the
      autonomous oscillatory firing patterns of biological pyloric pacemaker neurons,
      and it expressed the same stationary nonlinear responses to periodic forcing as
      its biological counterparts. This adds to our confidence in the model. These
      results strongly support the idea that the intact pyloric pacemaker group acts as
      a uniform low-dimensional deterministic nonlinear oscillator, and the regular
      pyloric oscillation is the outcome of cooperative behavior of strongly coupled
      neurons, having different dynamical and biophysical properties when isolated.

PMID- 11287487
TI  - Receptor-stimulated phospholipase A(2) liberates arachidonic acid and regulates
      neuronal excitability through protein kinase C.
AB  - Type B photoreceptors in Hermissenda exhibit increased excitability (e.g.,
      elevated membrane resistance and lowered spike thresholds) consequent to the
      temporal coincidence of a light-induced intracellular Ca(2+) increase and the
      release of GABA from presynaptic vestibular hair cells. Convergence of these pre-
      and postsynaptically stimulated biochemical cascades culminates in the activation
      of protein kinase C (PKC). Paradoxically, exposure of the B cell to light alone
      generates an inositol triphosphate-regulated rise in diacylglycerol and
      intracellular Ca(2+), co-factors sufficient to stimulate conventional PKC
      isoforms, raising questions as to the unique role of synaptic stimulation in the
      activation of PKC. GABA receptors on the B cell are coupled to G proteins that
      stimulate phospholipase A(2) (PLA(2)), which is thought to regulate the
      liberation of arachidonic acid (AA), an "atypical" activator of PKC. Here, we
      directly assess whether GABA binding or PLA(2) stimulation liberates AA in these
      cells and whether free AA potentiates the stimulation of PKC. Free fatty-acid was
      estimated in isolated photoreceptors with the fluorescent indicator acrylodan
      derivatized intestinal fatty acid-binding protein (ADIFAB). In response to 5
      microM GABA, a fast and persistent increase in ADIFAB emission was observed, and
      this increase was blocked by the PLA(2) inhibitor arachidonyltrifluoromethyl
      ketone (50 microM). Furthermore, direct stimulation of PLA(2) by melittin (10
      microM) increased ADIFAB emission in a manner that was kinetically analogous to
      GABA. In response to simultaneous exposure to the stable AA analogue oleic acid
      (OA, 20 microM) and light (to elevate intracellular Ca(2+)), B photoreceptors
      exhibited a sustained (>45 min) increase in excitability (membrane resistance and
      evoked spike rate). The excitability increase was blocked by the PKC inhibitor
      chelerythrine (20 microM) and was not induced by exposure of the cells to light
      alone. The increase in excitability in the B cell that followed exposure to light
      and OA persisted for > or =90 min when the pairing was conducted in the presence
      of the protein synthesis inhibitor anisomycin (1 microm), suggesting that the
      synergistic influence of these signaling agents on neuronal excitability did not
      require new protein synthesis. These results indicate that GABA binding to G
      protein-coupled receptors on Hermissenda B cells stimulates a PLA(2) signaling
      cascade that liberates AA, and that this free AA interacts with postsynaptic
      Ca(2+) to synergistically stimulate PKC and enhance neuronal excitability. In
      this manner, the interaction of postsynaptic metabotropic receptors and
      intracellular Ca(2+) may serve as the catalyst for some forms of associative
      neuronal/synaptic plasticity.

PMID- 11287488
TI  - Neural processing of gravito-inertial cues in humans. II. Influence of the
      semicircular canals during eccentric rotation.
AB  - All linear accelerometers, including the otolith organs, respond equivalently to
      gravity and linear acceleration. To investigate how the nervous system resolves
      this ambiguity, we measured perceived roll tilt and reflexive eye movements in
      humans in the dark using two different centrifugation motion paradigms (fixed
      radius and variable radius) combined with two different subject orientations
      (facing-motion and back-to-motion). In the fixed radius trials, the radius at
      which the subject was seated was held constant while the rotation speed was
      changed to yield changes in the centrifugal force. In variable radius trials, the
      rotation speed was held constant while the radius was varied to yield a
      centrifugal force that nearly duplicated that measured during the fixed radius
      condition. The total gravito-inertial force (GIF) measured by the otolith organs
      was nearly identical in the two paradigms; the primary difference was the
      presence (fixed radius) or absence (variable radius) of yaw rotational cues. We
      found that the yaw rotational cues had a large statistically significant effect
      on the time course of perceived tilt, demonstrating that yaw rotational cues
      contribute substantially to the neural processing of roll tilt. We also found
      that the orientation of the subject relative to the centripetal acceleration had
      a dramatic influence on the eye movements measured during fixed radius
      centrifugation. Specifically, the horizontal vestibuloocular reflex (VOR)
      measured in our human subjects was always greater when the subject faced the
      direction of motion than when the subjects had their backs toward the motion
      during fixed radius rotation. This difference was consistent with the presence of
      a horizontal translational VOR response induced by the centripetal acceleration.
      Most importantly, by comparing the perceptual tilt responses to the eye movement
      responses, we found that the translational VOR component decayed as the
      subjective tilt indication aligned with the tilt of the GIF. This was true for
      both the fixed radius and variable radius conditions even though the time course
      of the responses was significantly different for these two conditions. These
      findings are consistent with the hypothesis that the nervous system resolves the
      ambiguous measurements of GIF into neural estimates of gravity and linear
      acceleration. More generally, these findings are consistent with the hypothesis
      that the nervous system uses internal models to process and interpret sensory
      motor cues.

PMID- 11287489
TI  - Slow and fast (gamma) neuronal oscillations in the perirhinal cortex and lateral
      amygdala.
AB  - Most lesion studies emphasize the distinct contributions of the amygdala and
      perirhinal cortex to memory. Yet, the presence of strong reciprocal excitatory
      projections between these two structures suggests that they are functionally
      coupled. To gain some insight into this issue, the present study examined whether
      the close anatomical ties existing between perirhinal and lateral amygdala (LA)
      neurons are expressed in their spontaneous activity. To this end, multiple
      simultaneous recordings of single unit discharges and local field potentials were
      performed in the LA and perirhinal cortex in ketamine-xylazine anesthetized cats.
      The perirhinal cortex and LA exhibited a similar pattern of spontaneous activity.
      Recordings at both sites were dominated by a slow focal oscillation at 1 Hz onto
      which was superimposed a faster rhythm (approximately 30 Hz) whose amplitude
      fluctuated cyclically. Computing crosscorrelograms between focal waves recorded
      simultaneously in the perirhinal cortex and LA revealed a close relationship
      between their spontaneous activity. Even when recording sites were separated by
      as much as 8 mm, the slow focal oscillation remained highly correlated (r > or =
      0.7). In contrast, the correlation between fast oscillations was usually lower (r
      approximately 0.3). Perievent histograms of neuronal discharges revealed that the
      firing probability of most LA and perirhinal neurons increased during the depth
      negative component of the slow oscillation. In addition, respectively, 47 and 64%
      of LA and perirhinal neurons exhibited a significant modulation of firing
      probability in relation to the fast oscillations. Finally, crosscorrelating unit
      discharges simultaneously recorded in the LA and perirhinal cortex confirmed the
      presence of phase-related oscillatory events in both structures. In summary, our
      results suggest that the interconnections existing between the perirhinal cortex
      and LA can support the genesis of coherent neuronal activities at various
      frequencies. These results imply that cooperative interactions must be taking
      place between these structures.

PMID- 11287490
TI  - Frontal eye field sends delay activity related to movement, memory, and vision to
      the superior colliculus.
AB  - Many neurons within prefrontal cortex exhibit a tonic discharge between visual
      stimulation and motor response. This delay activity may contribute to movement,
      memory, and vision. We studied delay activity sent from the frontal eye field
      (FEF) in prefrontal cortex to the superior colliculus (SC). We evaluated whether
      this efferent delay activity was related to movement, memory, or vision, to
      establish its possible functions. Using antidromic stimulation, we identified 66
      FEF neurons projecting to the SC and we recorded from them while monkeys
      performed a Go/Nogo task. Early in every trial, a monkey was instructed as to
      whether it would have to make a saccade (Go) or not (Nogo) to a target location,
      which permitted identification of delay activity related to movement. In half of
      the trials (memory trials), the target disappeared, which permitted
      identification of delay activity related to memory. In the remaining trials
      (visual trials), the target remained visible, which permitted identification of
      delay activity related to vision. We found that 77% (51/66) of the FEF output
      neurons had delay activity. In 53% (27/51) of these neurons, delay activity was
      modulated by Go/Nogo instructions. The modulation preceded saccades made into
      only part of the visual field, indicating that the modulation was movement
      related. In some neurons, delay activity was modulated by Go/Nogo instructions in
      both memory and visual trials and seemed to represent where to move in general.
      In other neurons, delay activity was modulated by Go/Nogo instructions only in
      memory trials, which suggested that it was a correlate of working memory, or only
      in visual trials, which suggested that it was a correlate of visual attention. In
      47% (24/51) of FEF output neurons, delay activity was unaffected by Go/Nogo
      instructions, which indicated that the activity was related to the visual
      stimulus. In some of these neurons, delay activity occurred in both memory and
      visual trials and seemed to represent a coordinate in visual space. In others,
      delay activity occurred only in memory trials and seemed to represent transient
      visual memory. In the remainder, delay activity occurred only in visual trials
      and seemed to be a tonic visual response. In conclusion, the FEF sends diverse
      delay activity signals related to movement, memory, and vision to the SC, where
      the signals may be used for saccade generation. Downstream transmission of
      various delay activity signals may be an important, general way in which the
      prefrontal cortex contributes to the control of movement.

PMID- 11287491
TI  - Spatial distribution and subunit composition of GABA(A) receptors in the inferior
      olivary nucleus.
AB  - GABAergic inhibitory feedback from the cerebellum onto the inferior olivary (IO)
      nucleus plays an important role in olivo-cerebellar function. In this study we
      characterized the physiology, subunit composition, and spatial distribution of
      gamma-aminobutyric acid-A (GABA(A)) receptors in the IO nucleus. Using brain stem
      slices, we identified two types of IO neuron response to local pressure
      application of GABA, depending on the site of application: a slow desensitizing
      response at the soma and a fast desensitizing response at the dendrites. The
      dendritic response had a more negative reversal potential than did the somatic
      response, which confirmed their spatial origin. Both responses showed voltage
      dependence characterized by an abrupt decrease in conductance at negative
      potentials. Interestingly, this change in conductance occurred in the range of
      potentials wherein subthreshold membrane potential oscillations usually occur in
      IO neurons. Immunostaining IO sections with antibodies for GABA(A) receptor
      subunits alpha 1, alpha 2, alpha 3, alpha 5, beta 2/3, and gamma 2 and against
      the postsynaptic anchoring protein gephyrin complemented the electrophysiological
      observation by showing a differential distribution of GABA(A) receptor subtypes
      in IO neurons. A receptor complex containing alpha 2 beta 2/3 gamma 2 subunits is
      clustered with gephyrin at presumptive synaptic sites, predominantly on distal
      dendrites. In addition, diffuse alpha 3, beta 2/3, and gamma 2 subunit staining
      on somata and in the neuropil presumably represents extrasynaptic receptors.
      Combining electrophysiology with immunocytochemistry, we concluded that alpha 2
      beta 2/3 gamma 2 synaptic receptors generated the fast desensitizing (dendritic)
      response at synaptic sites whereas the slow desensitizing (somatic) response was
      generated by extrasynaptic alpha 3 beta 2/3 gamma 2 receptors.

PMID- 11287492
TI  - Analysis of firing correlations between sympathetic premotor neuron pairs in
      anesthetized cats.
AB  - The activity of sympathetic premotor neurons in the rostral ventrolateral medulla
      (subretrofacial nucleus) supports sympathetic vasomotor tone, but the factors
      that drive these premotor neurons' activity have not been determined. This study
      examines whether either direct interconnections between subretrofacial neurons or
      synchronizing common inputs to them are important for generating their tonic
      activity. Simultaneous extracellular single-unit recordings were made from 32
      pairs of sympathetic premotor neurons in the subretrofacial nucleus of chloralose
      anesthetized cats. Paired spike trains were either separated by spike shape from
      a single-electrode recording (14 pairs) or recorded from two electrodes less than
      250 microm apart (18 pairs). All neurons were inhibited by carotid baroreceptor
      stimulation and most had a spinal axon proven by antidromic stimulation from the
      spinal cord. Autocorrelation, inter-spike interval, and cardiac cycle-triggered
      histograms were constructed from the spontaneous activity of each neuron, and
      cross-correlation histograms covering several time scales were generated for each
      neuron pair. No significant peaks or troughs were found in short-term cross
      correlation histograms (2 ms bins, +/-100 ms range), providing no support for
      important local synaptic interactions. On an intermediate time scale (20 ms bins,
      +/-1 s range), cross-correlation revealed two patterns indicating shared,
      synchronizing inputs. Repeating peaks and troughs (19/32 pairs) were due to the
      two neurons' common cardiac rhythmicity, of presumed baroreceptor origin. Single,
      zero time-spanning peaks of 40--180 ms width were seen in 5/32 cases.
      Calculations based on the prevalence and strength of these synchronizing inputs
      indicate that most of the ensemble spike activity of the subretrofacial neuron
      population is derived from asynchronous sources (be they intrinsic or extrinsic).
      If synchronizing sources such as neuronal oscillators were responsible for more
      than a minor part of the drive, they would be multiple, dispersed, and weak.

PMID- 11287493
TI  - Theta-frequency facilitation of AMPA receptor-mediated synaptic currents in the
      principal cells of the medial septum.
AB  - Recent evidence suggests that Ca(2+)-permeable AMPA receptors display rapid,
      short-lasting current facilitation. In this study, we investigated the properties
      of AMPA receptor-mediated synaptic currents in medial septal neurons of the rat
      in an in vitro slice preparation. Immunocytochemistry with a selective antibody
      to the GluR2 subunit revealed that both choline acetyltransferase-containing and
      parvalbumin-containing neurons of the medial septum express no detectable GluR2
      subunit immunoreactivity. We used whole cell voltage-clamp recordings to measure
      synaptically evoked AMPA receptor-mediated currents from medial septal neurons
      following stimulation of midline afferents. The GYKI 52466 (50 microM)- and 2,3
      dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (20
      microM)-sensitive AMPA receptor-mediated component of the synaptic response was
      isolated by blocking GABA(A)- and N-methyl-D-aspartate receptor-mediated currents
      with 30 microM bicuculline and 100 microM 2-amino-5-phosphonovaleric acid,
      respectively. In some cases, patched cells were filled with Lucifer yellow (0.1%)
      and imaged using 2-photon laser scanning microscopy. AMPA receptor-mediated
      currents that were observed in large medial septal neurons (20--30 microm)
      displayed rectification. These currents were sensitive to external application of
      philanthotoxin-343 (PhTx-343, 50 microM), a potent, high-affinity antagonist of
      Ca(2+)-permeable, GluR2-lacking AMPA receptors. Rectifying AMPA receptor-mediated
      currents also displayed a rapid increase in amplitude when evoked five times at
      low frequency such as 6 Hz. In contrast to currents observed in large medial
      septal neurons, AMPA-receptor mediated currents evoked in the remaining small (8-
      11 microm) neurons were nonrectifying and displayed rapid synaptic depression
      when stimulated five times at 6 Hz. The currents evoked in these cells were
      unaffected by external application of PhTx-343 and were therefore GluR2
      containing AMPA receptors. The results of the present study demonstrate that the
      principal projection neurons of the medial septum contain PhTx-343-sensitive,
      GluR2-lacking AMPA receptors that display rapid current facilitation when
      stimulated at low frequencies.

PMID- 11287494
TI  - Electrophysiological characteristics of reactive astrocytes in experimental
      cortical dysplasia.
AB  - Neocortical freeze lesions have been widely used to study neuronal mechanisms
      underlying hyperexcitability in dysplastic cortex. Comparatively little attention
      has been given to biophysical changes in the surrounding astrocytes that show
      profound morphological and biochemical alterations, often referred to as reactive
      gliosis. Astrocytes are thought to aid normal neuronal function by buffering
      extracellular K(+). Compromised astrocytic K(+) buffering has been proposed to
      contribute to neuronal dysfunction. Astrocytic K(+) buffering is mediated,
      partially, by the activity of inwardly rectifying K(+) channels (K(IR)) and may
      involve intracellular redistribution of K(+) through gap-junctions. We
      characterized K(+) channel expression and gap-junction coupling between
      astrocytes in freeze-lesion-induced dysplastic neocortex. Whole cell patch-clamp
      recordings were obtained from astrocytes in slices from postnatal day (P) 16--P24
      rats that had received a freeze-lesion on P1. A marked increase in glial
      fibrillary acidic protein immunoreactivity was observed along the entire length
      of the freeze lesion. Clusters of proliferative (bromo-deoxyuridine nuclear
      staining, BrdU+) astrocytes were seen near the depth of the microsulcus.
      Astrocytes in cortical layer I surrounding the lesion were characterized by a
      significant reduction in K(IR). BrdU-positive astrocytes near the depth of the
      microsulcus showed essentially no expression of K(IR) channels but markedly
      enhanced expression of delayed rectifier K(+) (K(DR)) channels. These
      proliferative cells showed virtually no dye coupling, whereas astrocytes in the
      hyperexcitable zone adjacent to the microsulcus displayed prominent dye-coupling
      as well as large K(IR) and outward K(+) currents. These findings suggest that
      reactive gliosis is accompanied by a loss of K(IR) currents and reduced gap
      junction coupling, which in turn suggests a compromised K(+) buffering capacity.

PMID- 11287495
TI  - Functional organization of squirrel monkey primary auditory cortex: responses to
      pure tones.
AB  - The spatial organization of response parameters in squirrel monkey primary
      auditory cortex (AI) accessible on the temporal gyrus was determined with the
      excitatory receptive field to pure tone stimuli. Dense, microelectrode mapping of
      the temporal gyrus in four animals revealed that characteristic frequency (CF)
      had a smooth, monotonic gradient that systematically changed from lower values
      (0.5 kHz) in the caudoventral quadrant to higher values (5--6 kHz) in the
      rostrodorsal quadrant. The extent of AI on the temporal gyrus was approximately 4
      mm in the rostrocaudal axis and 2--3 mm in the dorsoventral axis. The entire
      length of isofrequency contours below 6 kHz was accessible for study. Several
      independent, spatially organized functional response parameters were demonstrated
      for the squirrel monkey AI. Latency, the asymptotic minimum arrival time for
      spikes with increasing sound pressure levels at CF, was topographically organized
      as a monotonic gradient across AI nearly orthogonal to the CF gradient. Rostral
      AI had longer latencies (range = 4 ms). Threshold and bandwidth co-varied with
      the CF. Factoring out the contribution of the CF on threshold variance, residual
      threshold showed a monotonic gradient across AI that had higher values (range =
      10 dB) caudally. The orientation of the threshold gradient was significantly
      different from the CF gradient. CF-corrected bandwidth, residual Q10, was
      spatially organized in local patches of coherent values whose loci were specific
      for each monkey. These data support the existence of multiple, overlying
      receptive field gradients within AI and form the basis to develop a conceptual
      framework to understand simple and complex sound coding in mammals.

PMID- 11287496
TI  - Calcium dynamics and electrophysiological properties of cerebellar Purkinje cells
      in SCA1 transgenic mice.
AB  - Cerebellar Purkinje cells (PCs) from spinocerebellar ataxia type 1 (SCA1)
      transgenic mice develop dendritic and somatic atrophy with age. Inositol 1,4,5
      trisphosphate receptor type 1 and the sarco/endoplasmic reticulum Ca(2+) ATPase
      pump, which regulate [Ca(2+)](i), are expressed at lower levels in these cells
      compared with the levels in cells from wild-type (WT) mice. To examine PCs in
      SCA1 mice, we used whole-cell patch clamp recording combined with fluorometric
      [Ca(2+)](i) and [Na(+)](i) measurements in cerebellar slices. PCs in SCA1 mice
      had Na(+) spikes, Ca(2+) spikes, climbing fiber (CF) electrical responses,
      parallel fiber (PF) electrical responses, and metabotropic glutamate receptor
      (mGluR)-mediated, PF-evoked Ca(2+) release from intracellular stores that were
      qualitatively similar to those recorded from WT mice. Under our experimental
      conditions, it was easier to evoke the mGluR-mediated secondary [Ca(2+)](i)
      increase in SCA1 PCs. The membrane resistance of SCA1 PCs was 3.3 times higher
      than that of WT cells, which correlated with the 1.7 times smaller cell body
      size. Most SCA1 PCs (but not WT) had a delayed onset (about 50--200 ms) to Na(+)
      spike firing induced by current injection. This delay was increased by
      hyperpolarizing prepulses and was eliminated by 4-aminopyridine, which suggests
      that this delay was due to enhancement of the A-like K(+) conductance in the SCA1
      PCs. In response to CF stimulation, most PCs in mutant and WT mice had rapid,
      widespread [Ca(2+)](i) changes that recovered in <200 ms. Some SCA1 PCs showed a
      slow, localized, secondary Ca(2+) transient following the initial CF Ca(2+)
      transient, which may reflect release of Ca(2+) from intracellular stores. Thus,
      with these exceptions, the basic physiological properties of mutant PCs are
      similar to those of WT neurons, even with dramatic alteration of their morphology
      and downregulation of Ca(2+) handling molecules.

PMID- 11287497
TI  - Dopamine-mediated volume transmission in midbrain is regulated by distinct
      extracellular geometry and uptake.
AB  - Somatodendritic release of dopamine (DA) in midbrain is, at least in part,
      nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic.
      Thus somatodendritic DA mediates volume transmission, with an efficacy regulated
      by the diffusion and uptake characteristics of the local extracellular
      microenvironment. Here, we quantitatively evaluated diffusion and uptake in
      substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area
      (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters
      that govern diffusion, extracellular volume fraction (alpha) and tortuosity
      (lambda), together with linear uptake (k'), were determined for
      tetramethylammonium (TMA(+)), and for DA, using point-source diffusion combined
      with ion-selective and carbon-fiber microelectrodes. TMA(+)-diffusion
      measurements revealed a large alpha of 30% in SNc, SNr, and VTA, which was
      significantly higher than the 22% in cortex. Values for lambda and k' for TMA(+)
      were similar among regions. Point-source DA-diffusion curves fitted theory well
      with linear uptake, with significantly higher values of k' for DA in SNc and VTA
      (0.08--0.09 s(-1)) than in SNr (0.006 s(-1)), where DA processes are sparser.
      Inhibition of DA uptake by GBR-12909 caused a greater decrease in k' in SNc than
      in VTA. In addition, DA uptake was slightly decreased by the norepinephrine
      transport inhibitor, desipramine in both regions, although this was statistically
      significant only in VTA. We used these data to model the radius of influence of
      DA in midbrain. Simulated release from a 20-vesicle point source produced DA
      concentrations sufficient for receptor activation up to 20 microm away with a DA
      half-life at this distance of several hundred milliseconds. Most importantly,
      this model showed that diffusion rather than uptake was the most important
      determinant of DA time course in midbrain, which contrasts strikingly with the
      striatum where uptake dominates. The issues considered here, while specific for
      DA in midbrain, illustrate fundamental biophysical properties relevant for all
      extracellular communication.

PMID- 11287498
TI  - Isolation of the kernel for respiratory rhythm generation in a novel preparation:
      the pre-Botzinger complex "island".
AB  - The pre-Botzinger complex (pre-BotC), a bilaterally distributed network of
      rhythmogenic neurons within the ventrolateral medulla, has been proposed to be
      the critical locus for respiratory rhythm generation in mammals. To date, thin
      transverse medullary slice preparations that capture the pre-BotC have served as
      the optimal experimental model to study the region's inherent cellular and
      network properties. We have reduced the thin slices to isolated pre-BotC
      "islands" to further establish whether the pre-BotC has intrinsic rhythmicity and
      is the kernel for rhythmogenesis in the slice. We recorded neuron population
      activity locally in the pre-BotC with macroelectrodes and fluorescent imaging of
      Ca(2+) activities with Calcium Green-1AM dye before and after excising the
      island. The isolated island remained rhythmically active with a population burst
      profile similar to the inspiratory burst in the slice. Rhythmic population
      activity persisted in islands after block of GABA(A)ergic and glycinergic
      synaptic inhibition. The loci of pre-BotC Ca(2+) activity imaged in thin slices
      and islands were similar, and imaged pre-BotC neurons exhibited synchronized
      flashing after blocking synaptic inhibition. Population burst frequency increased
      monotonically as extracellular potassium concentration was elevated, consistent
      with mathematical models consisting entirely of an excitatory network of
      synaptically coupled pacemaker neurons with heterogeneous, voltage-dependent
      bursting properties. Our results provide further evidence for a rhythmogenic
      kernel in the pre-BotC in vitro and demonstrate that the islands are ideal
      preparations for studying the kernel's intrinsic properties.

PMID- 11287499
TI  - Motor control of low-threshold motor units in the human trapezius muscle.
AB  - The firing pattern of low-threshold motor units was examined in the human
      trapezius and first dorsal interosseous (FDI) muscles during slowly augmenting,
      low-amplitude contractions that were intended to mimic contractile activity in
      postural muscles. The motor unit activity was detected with a special needle
      electrode and was analyzed with the assistance of computer algorithms. The
      surface electromyographic (EMG) signal was recorded. Its root-mean-square (RMS)
      value was calculated and presented to the subject who used it to regulate the
      muscle force level. In the trapezius, there was minimal, if any, firing rate
      modulation of early recruited motor units during slow contractions (< or =1%
      EMG(max)/s), and later recruited motor units consistently presented higher peak
      firing rates. As the force rate of the contraction increased (3% EMG(max)/s), the
      firing rates of the motor units in the trapezius approached an orderly
      hierarchical pattern with the earliest recruited motor units having the greatest
      firing rate. In contrast, and as reported previously, the firing rates of all
      motor units in the FDI always presented the previously reported hierarchical
      "onion-skin" pattern. We conclude that the low-threshold motor units in the
      postural trapezius muscle, that is the motor units that are most often called on
      to activate the muscle in postural activities, have different control features in
      slow and fast contractions. More detailed analysis revealed that, in the low
      force-rate contractions of the trapezius, recruitment of new motor units
      inhibited the firing rate of active motor units, providing an explanation for the
      depressed firing rate of the low-threshold motor units. We speculate that Renshaw
      cell inhibition contributes to the observed deviation of the low-threshold motor
      units from the hierarchical onion-skin pattern.

PMID- 11287500
TI  - Frequency dependence of spike timing reliability in cortical pyramidal cells and
      interneurons.
AB  - Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit
      subthreshold oscillations when depolarized by constant current injection. For
      both types of neurons, the frequencies of these oscillations for current
      injection just below spike threshold were 2--10 Hz. Above spike threshold,
      however, the subthreshold oscillations in pyramidal cells remained low, but the
      frequency of oscillations in interneurons increased up to 50 Hz. To explore the
      interaction between these intrinsic oscillations and external inputs, the
      reliability of spiking in these cortical neurons was studied with sinusoidal
      current injection over a range of frequencies above and below the intrinsic
      frequency. Cortical neurons produced 1:1 phase locking for a limited range of
      driving frequencies for fixed amplitude. For low-input amplitude, 1:1 phase
      locking was obtained in the 5- to 10-Hz range. For higher-input amplitudes,
      pyramidal cells phase-locked in the 5- to 20-Hz range, whereas interneurons phase
      locked in the 5- to 50-Hz range. For the amplitudes studied here, spike time
      reliability was always highest during 1:1 phase-locking, between 5 and 20 Hz for
      pyramidal cells and between 5 and 50 Hz for interneurons. The observed
      differences in the intrinsic frequency preference between pyramidal cells and
      interneurons have implications for rhythmogenesis and information transmission
      between populations of cortical neurons.

PMID- 11287501
TI  - Spinal allografts of adrenal medulla block nociceptive facilitation in the dorsal
      horn.
AB  - Transplantation of chromaffin cells into the lumbar subarachnoid space has been
      found to produce analgesia, most conspicuously against chronic neuropathic pain.
      To ascertain the neurophysiological mechanism, we recorded electrical activity
      from wide-dynamic-range dorsal horn neurons in vivo, measuring the short-lasting
      homosynaptic facilitatory effect known as windup, which is induced by repetitive
      C-fiber input. Rats were given adrenal medulla allografts, or, as controls,
      striated-muscle allografts. The adrenal-transplanted rats showed analgesia 3--4
      wk after transplantation, measured as a reduction in flinching reflexes 30--55
      min after subcutaneous formalin injection. Recordings were made under halothane
      anesthesia, 3--7 days following the behavioral testing. The average C-fiber
      response and subsequent afterdischarge were facilitated severalfold in control
      rats by 1-Hz cutaneous electrical stimulation. Such facilitation was essentially
      absent in adrenal-transplanted animals and also in the A-fiber response of both
      preparations. Extirpation of transplanted tissue several hours prior to recording
      did not significantly affect this difference. In conclusion, the adrenal
      transplants block short-term spinal nociceptive facilitation, probably by
      stimulating some persistent cellular process that may be an important
      determinant, but not the only one, of their analgesic effect.

PMID- 11287502
TI  - Credentials for peripheral angioplasty: comments on society of cardiac
      angiography and intervention revisions.

PMID- 11287503
TI  - Society of Cardiovascular & Interventional Radiology position statement on
      radiation safety.

PMID- 11287504
TI  - Use of metallic stents and balloons in the esophagus and gastrointestinal tract.
AB  - The majority of malignant and benign strictures in the esophagus and GI tract can
      be treated with use of minimally invasive alternatives to surgery such as balloon
      dilation or metallic stents. Virtually any obstructing lesion in the esophagus,
      stomach, duodenum, colon, and rectum can be treated with these methods with use
      of interventional radiologic or endoscopic techniques. In general, metallic
      stents are reserved for malignant strictures and balloon dilation is indicated
      for benign lesions. Patients with malignant esophageal fistulas and perforations
      can be palliated effectively and promptly by sealing the fistula or leak by
      deployment of a covered stent. Patients with malignant disease may benefit from a
      treatment regime that includes metallic stent placement, chemotherapy, radiation
      therapy and/or brachytherapy, although the efficacy of such combined therapies
      has yet to be defined. Further refinements to stent design are required. The
      ideal stent would be resistant to tumor ingrowth and migration. Placing a coating
      material on uncovered stents to prevent tumor ingrowth may achieve these aims.
      Finally, a biodegradable stent that dissolves before the development of intimal
      hyperplasia might enable stents to be used to treat benign strictures.

PMID- 11287505
TI  - The 6-F nitinol TrapEase inferior vena cava filter: results  of a prospective
      multicenter trial.
AB  - PURPOSE: The authors report the first results of a new 6-F symmetrically designed
      permanent nitinol inferior vena cava (IVC) filter, the Cordis TrapEase, evaluated
      in a multicenter prospective study with 6-months of follow-up. MATERIALS AND
      METHODS: A total of 65 patients (29 men, 36 women) who ranged in age from 37 to
      96 years (mean age, 68 years) and who were at high risk of pulmonary embolism
      (PE) were enrolled in 12 centers in Europe and Canada. The study was approved by
      the institutional review boards at all centers. Study objectives were to evaluate
      filter effectiveness, filter stability, and caval occlusion. Indications for
      filter placement were deep vein thrombosis with recurrent thromboembolism and/or
      free-floating thrombus with contraindication to anticoagulation in 37 patients,
      and complications in achieving adequate anticoagulation in 28 patients. Follow-up
      included clinical examination, plain film, Doppler ultrasound, CT scan, and
      nuclear medicine. RESULTS: The analysis of the data revealed a technical success
      of 95.4% (three filter-system related implantations not at the intended site, no
      events of filter tilting) and a clinical success of 100% at 6 months (no cases of
      symptomatic PE), the study primary endpoint. There were no cases (0%) of filter
      migration, insertion site thrombosis, filter fracture, or vessel wall
      perforation. During the study period, there were two cases of filter thrombosis:
      one case of early symptomatic thrombosis that was successfully treated in the
      hospital, and one case of nonsymptomatic filter thrombosis detected at 1-month
      follow-up, with spontaneous recanalization at 3 months. In the latter patient,
      some residual thrombus was still detected at 6 months. Of the study population of
      65 patients, there were 23 deaths. These deaths were not related to the device or
      the implantation procedure but to the underlying disease process. CONCLUSION:
      This study demonstrates the new nitinol permanent IVC filter to be a safe and an
      effective device, with a low overall complication rate, for use in patients with
      thromboembolic disease at high risk of PE.

PMID- 11287506
TI  - Thrombolysis of clotted hemodialysis grafts with tissue-type plasminogen
      activator.
AB  - PURPOSE: To evaluate prospectively the efficacy of treating thrombosed
      hemodialysis arteriovenous polytetrafluoroethylene (PTFE) grafts using tissue
      type plasminogen activator (tPA) and percutaneous transluminal angioplasty (PTA).
      MATERIALS AND METHODS: Forty-two sequential thrombosed PTFE dialysis grafts in 33
      patients presented for declotting. All 42 grafts were treated with a modified
      lysis and PTA technique with use of 2 mg tPA and 3,000-5,000 U heparin in a total
      volume of 5 mL, administered into the graft via an angiocatheter. The elapsed
      time from tPA injection until completion was recorded. Prospective data
      collection included demographic information, technical details of the procedure,
      immediate outcomes, complications, and patency rates. RESULTS: Technical success,
      defined as complete graft recanalization with a palpable thrill after treatment
      plus successful hemodialysis, was achieved in all cases, except five. These five
      cases were deliberate graft closures due to inadequacy of the outflow veins to
      support an arteriovenous graft after successful lysis. Mean lysis time was 40.8
      minutes and mean room procedure time after the lysis period was 65.4 minutes.
      Eight procedure-related complications occurred (two major and six minor). The
      follow-up period was 4-241 days, with an estimated mean of 157 days. The 30-day
      and 90-day primary patency rates were 57% and 50%, respectively. CONCLUSIONS:
      Treatment of thrombosed PTFE dialysis grafts with use of 2 mg tPA and 3,000 U of
      heparin is safe and effective. Use of this modified lysis and PTA technique
      allows an expeditious procedure in the angiography suite. However, this technique
      precludes imaging of the outflow veins before treatment, so that grafts entering
      diffusely diseased veins may need to be closed after successful lysis.

PMID- 11287507
TI  - Legs For Life national screening program for peripheral vascular disease:
      addressing a major public health need.

PMID- 11287508
TI  - Liver abscess after transcatheter oily chemoembolization for hepatic tumors:
      incidence, predisposing factors, and clinical outcome.
AB  - PURPOSE: To evaluate the incidence of, predisposing factors for, and clinical
      outcome of liver abscess developing in patients with hepatic tumors after
      transcatheter oily chemoembolization (TOCE). MATERIALS AND METHODS: During the
      past 6-year period, 2,439 patients with hepatic tumors underwent a total of 6,255
      TOCE procedures. With a retrospective review of medical records, the authors
      evaluated the occurrence of liver abscess, the statistical significance of
      potential predisposing factors including portal vein obstruction, metastatic
      tumors, biliary abnormalities (type 1, simple biliary obstruction; type 2, status
      prone to ascending biliary infection), malignant gastrointestinal mucosal
      lesions, and additional gelatin sponge particle embolization in liver abscess
      formation, and the clinical outcome of abscess. RESULTS: Fifteen liver abscesses
      occurred in 14 patients (0.2%). Liver abscesses developed in three of 987 (0.3%)
      TOCE procedures for portal vein obstruction, three of 114 (2.6%) procedures for
      metastatic tumors, one of 49 (1.8%) for type 1 biliary abnormality, four of 55
      (7.4%) for type 2 biliary abnormality, two of 18 (11.1%) for malignant
      gastrointestinal mucosal lesion, and nine of 2,108 (0.4%) for additional gelatin
      sponge particle embolization. Univariate and multivariate statistical analysis
      showed that type 2 biliary abnormality was a significant predisposing factor. The
      mortality related to liver abscess occurred in two patients (13.3%). Thirteen
      liver abscesses were successfully treated with parenteral antibiotics and
      percutaneous catheter drainage. However, irreversible deterioration of liver
      function occurred in two patients. Two of nine further TOCE procedures in three
      patients caused recurrent septicemia and liver abscess. CONCLUSION: The biliary
      abnormality prone to ascending biliary infection was the most important
      predisposing factor to the development of liver abscess after TOCE. Postembolic
      liver abscess could be effectively managed with percutaneous catheter drainage.

PMID- 11287509
TI  - Determinants of postembolization syndrome after hepatic chemoembolization.
AB  - PURPOSE: Postembolization syndrome (PES) occurs in the majority of patients
      undergoing hepatic chemoembolization, and is the major reason for hospitalization
      after the procedure. The ability to identify which groups of patients are at
      increased or decreased risk of PES would be useful to better counsel patients, to
      minimize toxicity, and to plan inpatient versus outpatient therapy. MATERIALS AND
      METHODS: Seventy hepatic chemoembolization procedures were performed in 29
      patients using cytotoxic drugs mixed with Ethiodol and polyvinyl alcohol. The
      following procedural variables were retrospectively assessed and evaluated for
      association with PES and length of postprocedural hospitalization: gallbladder
      embolization, lobe embolized, percentage liver volume embolized, percentage
      embolized volume occupied by tumor, previous embolization of the same territory,
      and dose of chemoembolic emulsion. Logistic regression was used to quantify the
      relative effect of each procedural variable. RESULTS: Gallbladder embolization
      and dose administered were associated with an increased risk of PES and an
      extended hospitalization, with odds ratios of 2.8 and 3.0, and 3.0 and 4.6,
      respectively. Previous embolization was associated with a decreased risk of both
      PES and extended hospitalization, with odds ratios of 0.5 and 0.4, respectively.
      There was a statistical trend toward significance for gallbladder embolization (P
      = .06), dose administered (P = .07), and previous embolization (P = .14).
      CONCLUSION: Clinically relevant predictors of the severity of PES and length of
      postprocedural hospitalization may exist. Avoiding embolization of the
      gallbladder reduces the risk of PES. Re-embolization of previously treated
      vessels is associated with decreased toxicity and may assist in selecting
      patients for treatment on an outpatient basis, especially when a reduced dose is
      required.

PMID- 11287510
TI  - Long-term results of balloon-occluded retrograde transvenous obliteration for the
      treatment of gastric varices and hepatic encephalopathy.
AB  - PURPOSE: To evaluate the long-term results of balloon-occluded retrograde
      transvenous obliteration (B-RTO) for the treatment of gastric varices (GV) and
      hepatic encephalopathy. MATERIALS AND METHODS: A total of 43 patients who had
      undergone B-RTO were evaluated, 32 with GV, two with hepatic encephalopathy, and
      nine with both. All but one had been consecutively followed up with
      gastrointestinal endoscopy for more than 1 year (3-60 months; mean, 30.44
      months). Collateral veins of gastric varices were graded using balloon-occluded
      retrograde left adrenal venography. The relation of both worsening of esophageal
      varices (EV) and improved Child-Pugh score after B-RTO to the grades of
      collateral vein development was analyzed. The relapse-free survival and the
      prognostic factors for survival after B-RTO were also assessed. RESULTS: GV
      disappeared or decreased markedly in size, and hepatic encephalopathy was
      completely cured in all patients. Improvement in Child-Pugh score was observed in
      21 patient (50.0%) 6 months after B-RTO, but in only 11 patients (25.6%) 1 year
      after B-RTO. Worsening of EV was seen in eight patients and was related to a
      worsened grade of collateral veins. Cumulative relapse-free survival rate was
      90.8% at 1 year and 87.4% at 3 years after B-RTO. The most significant prognostic
      factor was Child-Pugh classification (relative risk: 4.16) CONCLUSION: B-RTO is a
      safe and effective treatment for patients with GV and hepatic encephalopathy. The
      most important prognostic factors are the extent of Child-Pugh classification.

PMID- 11287511
TI  - Aortic side branch embolization before endovascular aneurysm repair: incidence of
      type II endoleak.
AB  - PURPOSE: To assess the feasibility of embolization of aortic side branches and
      its impact on the incidence of type II endoleak after endovascular aneurysm
      repair. MATERIALS AND METHODS: Endovascular aneurysm repair was performed in 74
      patients. Aortic side branch vessels were evaluated on the preoperative angiogram
      and computed tomography (CT) and, where embolization of lumbar and inferior
      mesenteric vessels was considered technically possible, this was attempted prior
      to endovascular repair. Follow-up CT was used to assess the presence of type II
      endoleak. RESULTS: Seventy-two patients were followed up for longer than 1 month.
      Embolization was attempted in 25 cases, successfully in 10, with partial success
      in 11, and failure in four. Twenty patients with successful or partly successful
      preoperative embolization were discharged and followed-up. Four (20%) had
      demonstrable type II endoleak during follow-up, with two of these persisting at
      latest follow-up. Of 43 patients without previous embolization, there were 10
      (23.3%) type II endoleaks during the follow-up period, four of these persisting.
      In cases with type II endoleak, mean sac diameter change was -0.5 mm in the cases
      with previous embolization and +3.1 mm without. The mean period to onset of type
      II endoleak was 6.9 months without, and 15.3 months with, previous embolization.
      CONCLUSION: Although the cohort size is below a level that would confer
      significance, the trend of these findings is such as to suggest a lack of
      influence of aortic side branch embolization on the incidence of type II endoleak
      during the follow-up period.

PMID- 11287512
TI  - Sonographic needle guidance in cholangiography in children.
AB  - PURPOSE: To evaluate feasibility and benefits of sonographic guidance of
      percutaneous transhepatic cholangiography (PTC) in children with liver
      transplants. MATERIALS AND METHODS: The authors prospectively followed 24 PTC
      procedures in 19 pediatric patients (11 females, 8 males; age 3 months to 17
      years) randomized to fluoroscopic or sonographic guidance. The number of needle
      passes, the contrast material dose, fluoroscopy time, and procedure time for each
      procedure were recorded. All patients were transplant recipients-six whole and 13
      reduced-size grafts. Cases were randomly assigned to two groups: group I,
      fluoroscopically guided PTC (12 procedures); group II, sonographically guided PTC
      (12 procedures). RESULTS: The technical success rate was 92% (11 of 12) for each
      group. In group I, there were two procedure-related complications: postprocedural
      fever caused by biliary to portal vein fistula, and peritoneal bleeding requiring
      surgery. In group II, there were no procedure-related complications. A mean of
      8.2 +/- 3.7 needle passes were required in group I compared to only 2.0 +/- 1.3
      in group II (P < .0001). A mean contrast material dose of 19.5 mL +/- 13.4 was
      required in group I compared to only 2.5 mL +/- 1.9 in group II (P < .001). A
      mean procedure time of 15.7 minutes +/- 7.4 was required in group I compared to
      only 6.1 minutes +/- 4.5 in group II (P < .001). A mean fluoroscopy time of 10.4
      minutes +/- 5.0 was required in group I compared to only 1.0 minutes +/- 0.7 in
      group II (P < .0001). CONCLUSION: In pediatric patients who have undergone liver
      transplantation, sonographic guidance significantly decreases the number of
      needle passes, contrast material dose, and fluoroscopy time required for PTC.

PMID- 11287513
TI  - Perivascular release of insulin-like growth factor-1 limits neointima formation
      in the balloon-injured artery by redirecting smooth muscle cell migration.
AB  - PURPOSE: Insulin-like growth factor-1 (IGF-1) is a potent chemoattractant to
      vascular smooth muscle cells (SMCs). The authors hypothesize that perivascular
      release of IGF-1 in vivo can direct migration of SMCs away from the lumen and
      reduce neointima formation in a rabbit model of arterial balloon injury.
      MATERIALS AND METHODS: Balloon angioplasty of the common femoral arteries was
      performed in adult male New Zealand White rabbits (n = 8 per treatment group) and
      controlled release microspheres delivering either IGF-1 or blank control
      treatment were implanted perivascularly at the angioplasty site prior to surgical
      closure. At 7 days, five arteries per group were harvested and cross-sections
      were subjected to anti-PCNA (proliferating cell nuclear antigen) immunostaining
      to determine the number and distribution of proliferating SMCs. At 28 days, the
      remaining three arteries per group were harvested and sections were evaluated for
      intima-to-media (I/M) ratios by means of VVG-Masson staining. One-way analysis of
      variance with Fisher protected least significant difference post hoc testing was
      used to determine statistical significance at P < .05. RESULTS: At 7 days,
      PCNA(+) medial SMCs assumed a significantly more peripheral (ie, further from
      lumen) distribution in the vessel wall with use of perivascular IGF-1 than with
      use of blank treatment (P < .05). Overall SMC proliferation was not significantly
      different, thus the change in distribution was likely due to directionally
      altered SMC migration. At 28 days, perivascular IGF-1 significantly decreased I/M
      ratios by 44% relative to control treatment (P < .05). CONCLUSIONS: Perivascular
      release of IGF-1 can directionally guide SMC migration away from the lumen and
      reduce neointima in the balloon-injured artery. This novel strategy might have
      implications in the development of antirestenosis therapies.

PMID- 11287514
TI  - Biocompatibility and performance of the Wallstent and several covered stents in a
      sheep iliac artery model.
AB  - PURPOSE: To compare the biocompatibility and performance of various stent-grafts
      to those of a bare stent in an ovine model with a subchronic (3 months) endpoint.
      MATERIALS AND METHODS: Three different types of stent-grafts (ePTFE/nitinol, n =
      8; polyester/nitinol, n = 8; and polycarbonate urethane/cobalt-alloy, n = 8) and
      a bare stent as a control (Ni-Co-Ti-steel-alloy, n = 8) were implanted in the
      iliac arteries in eight female sheep. One type of each stent-graft was implanted
      per animal, two implants at each side. The implantation sites for each type
      varied from animal to animal. Angiographic control and intravascular ultrasound
      (IVUS) imaging were performed before and after implantation, after 2 months, and
      before explantation at 3 months and were used to characterize patency and to
      assess intimal hyperplasia. After 3 months, the implants were retrieved and
      subjected to histologic evaluation (after methacrylate embedding, cutting, and
      histologic staining) to characterize the biologic response. RESULTS: Implantation
      was technically successful in all procedures. At 2 and 3 months after
      implantation, all segments in which stents had been implanted were patent. Marked
      neointima formation was found in the polyester-covered stent-graft that showed
      significant luminal narrowing of 50%, compared to the ePTFE-covered (24%) and
      polycarbonate urethane-covered endoprostheses (22%), as well as the bare stent
      (Wallstent; 9%; P < .001). A minimal inflammatory vessel wall reaction was
      demonstrated for the polyester-covered and ePTFE-covered endoprostheses; the
      polycarbonate urethane-covered stent-graft's response was demonstrable but not
      significantly different from that of the Wallstent. At 3 months, the ePTFE
      covered stent-graft showed incomplete (>90%) endothelial coverage; in the other
      endoprostheses, complete but partially immature endothelialization was found.
      CONCLUSION: All stent-grafts induced an inflammatory vessel wall reaction with
      neointimal hyperplasia. The polyester-covered endoprosthesis caused a marked
      reaction with 50% luminal stenosis. Endothelialization was retarded with the
      ePTFE-covered stent-graft. The bare stent performed best in regard to neointimal
      formation and caused the least inflammatory response.

PMID- 11287515
TI  - Bifurcated drum occluder endograft for treatment of abdominal aortic aneurysm: an
      experimental study in dogs.
AB  - PURPOSE: To evaluate a new, low profile, home-made, bifurcated drum occluder
      endograft (BDOEG), designed for percutaneous, transcatheter treatment of
      abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: AAA was created in 10
      dogs with over-dilated Palmaz stents. To prevent back filling, the lumbar
      arteries, inferior mesenteric artery, and common internal iliac arteries were
      embolized. The BDOEG was constructed of a drum occluder device and two PTFE
      endografts. The drum device consisted of a modified Z stent with Dacron stretched
      across and held within the ends of the stent, each with two 8 x 6-mm slits
      through which PTFE endografts were delivered. The PTFE endografts were 8 mm in
      diameter and 9.5 cm in length. Preloaded, the BDOEG was delivered through a 10-F
      sheath from both femoral arteries in a three-step procedure. All 10 animals were
      treated with BDOEG. Aortography was performed immediately, 6 weeks, and 12 weeks
      after stent-graft placement. Five animals were killed at 6 weeks and five were
      killed at 3 months. Gross and histologic evaluation was performed. RESULTS: The
      infrarenal aortic diameters and both external iliac arteries ranged from 8.0 mm
      to 10.3 mm (mean, 9.4 mm +/- 0.6) and from 5.2 mm to 6.8 mm (mean, 5.8 mm +/-
      0.5), respectively. Creation of the AAA was successful in all 10 dogs. AAA
      diameters ranged from 13.7 mm to 15.9 mm (mean, 14.9 mm +/- 0.7). Complete
      exclusion of the AAA was achieved immediately after BDOEG placement and aneurysms
      remained excluded without perigraft leak to the time of killing in all 10
      animals. There was a high incidence of aortoiliac limb occlusion. Occlusion of 12
      aortoiliac limbs (60%) caused by intimal hyperplasia at the distal end of the
      endografts in iliac arteries developed in nine animals (90%). In six animals
      (60%), one limb occluded and, in three animals (30%), there was occlusion of both
      limbs. CONCLUSION: This study suggests a new approach for treatment of AAA. BDOEG
      use reduces sheath size for endograft delivery and may eliminate the need for a
      surgical cut down on femoral arteries. Tapering of the iliac ends of endografts
      to the size of the artery will be needed to prevent distal intimal hyperplasia.

PMID- 11287516
TI  - MR imaging of vascular stents: effects of susceptibility, flow, and
      radiofrequency eddy currents.
AB  - PURPOSE: The purpose of this in vitro study was to examine the various sources of
      artifacts in magnetic resonance (MR) imaging and angiography of vascular stents.
      MATERIALS AND METHODS: Five low-artifact stents-Wallstent (cobalt alloy),
      Memotherm (nitinol), Perflex (stainless steel), Passager (tantalum), and Smart
      (nitinol)-were imaged in a vascular flow phantom, consisting of a thin-walled
      cellulose vessel model connected to a pump system. The echo time and the
      angulation of the stents with respect to the direction of the main magnetic field
      were varied. Spin echo and gradient echo images as well as three-dimensional MR
      angiograms were obtained to study the effects of flow, magnetic susceptibility,
      and radiofrequency-induced eddy currents. RESULTS: Susceptibility artifacts were
      restricted to the stents' direct environment and were mildest at short echo times
      and with the stents aligned with the main magnetic field. Nitinol stents showed
      less artifacts than steel stents did. Radiofrequency artifacts obscuring the
      stent lumen and flow-related lumen displacement were seen in all stents. The
      extent to which these occurred depended on strut geometry and orientation.
      CONCLUSIONS: For low-artifact stents, the material the stent is made of is not
      the only important factor in the process of artifact formation. Susceptibility
      artifacts, radiofrequency eddy currents and flow-related artifacts all contribute
      to the image distortion, and are dependent on the geometry and orientation of the
      struts and on the orientation of the stent in the main magnetic field.

PMID- 11287517
TI  - Pleurx tunneled catheter in the management of malignant ascites.
AB  - The authors report their experience with the Pleurx tunneled catheter in patients
      with end-stage abdominal carcinomatosis and intractable ascites. Ten patients
      with intractable ascites and abdominal carcinomatosis underwent placement of
      tunneled Pleurx catheters. The catheters were placed with combined US and
      fluoroscopic guidance. Patients' charts were reviewed for procedural
      complications, serum albumin levels, infection, efficacy of catheters in
      providing effective drainage of ascites, and duration of catheter patency. There
      were no procedural complications. The serum albumin level decreased from 2.7 g/L
      to 2.3 at 3 weeks and 2.4 g/L at 6 weeks. There were no catheter infections. Some
      patients required continuous drainage, whereas others were successfully treated
      by drainage once per week. Mean catheter survival was 70 days. In patients with
      end-stage abdominal carcinomatosis complicated by malignant ascites, the Pleurx
      tunneled catheter can provide effective palliation and alleviated the need for
      repeated percutaneous paracentesis.

PMID- 11287518
TI  - Sheathless technique of Ash Split-Cath insertion.
AB  - A novel technique for insertion of the Ash Split-Cath without a peel-away sheath
      to decrease the potential for air embolism is described. A retrospective review
      of 62 attempted Ash Split-Cath insertions at three hospitals was made. Conversion
      to the usual technique using a sheath was necessary in four cases, mostly because
      of extensive scarring from previous catheters. There was no air embolus,
      hematoma, or immediate catheter malfunction. The authors believe that the
      occurrence of air embolism during placement of Ash Split-Cath may be lessened by
      eliminating the use of a peel-away sheath.

PMID- 11287519
TI  - Intraarterial low-dose cisplatin via an indwelling port and concurrent
      radiotherapy for invasive bladder cancer.
AB  - Thirteen patients with invasive bladder cancer who had residual tumor after
      transurethral resections, were treated with consecutive intraarterial (IA)
      cisplatin (15 mg/d; total, 150 mg) and concurrent radiation (1.8 Gy/d; total,
      30.6 Gy). All patients received unilateral or bilateral placement of vascular
      access devices (VAD) to perform daily cisplatin infusion after alteration of
      intrapelvic blood flow by coil embolizations. Tumor response was evaluated by
      transurethral biopsy 2 weeks after treatment. Complete response, defined as no
      viable tumor cell in the biopsy specimen, was achieved in seven patients (54%).
      After a median follow-up of 30 months (range, 12-48 months), 10 patients (77%)
      were alive, five (38%) of whom had no recurrence. Two cancer-related deaths were
      observed. All complete response cases survived with a median follow-up of 35
      months (range, 25-48 months). Cause-specific and disease-free survival rates at 4
      years were 85% and 28%, respectively. The regimen was well-tolerated, with no
      dose-limiting toxic events. There were no VAD-related complications. Consecutive
      IA low-dose cisplatin and concurrent radiation may be an acceptable alternative
      treatment for patients with bladder cancer who are not suitable for systemic
      chemotherapy. The use of a VAD contributed to successful consecutive IA
      infusions.

PMID- 11287520
TI  - Anomalous left adrenal venous drainage directly into the inferior vena cava.
AB  - Primary hyperaldosteronism is a potential cause of hypertension. Unilateral
      adrenal adenoma and bilateral adrenal cortical hyperplasia are the most common
      causes of primary hyperaldosteronism. Adrenal venous sampling is employed as the
      gold standard test to differentiate between these two different causes when the
      results of other studies in the work-up protocol are non-diagnostic or ambiguous.
      Adrenal venous sampling can be a challenging procedure, especially in the
      presence of anomalous venous drainage patterns. Knowledge of normal adrenal
      venous anatomy, as well as possible variants, is therefore important to ensure a
      successful procedure. The authors describe an unusual variant of left adrenal
      venous drainage directly into the IVC.

PMID- 11287521
TI  - Hyperperfusion syndrome of the left hand after percutaneous transluminal
      angioplasty and stent placement in a subclavian artery stenosis.

PMID- 11287522
TI  - Multi-branched stent-graft for type III thoracoabdominal aortic aneurysm.

PMID- 11287523
TI  - Gadolinium arteriography complicated by acute pancreatitis and acute renal
      failure.

PMID- 11287524
TI  - Spontaneous nontraumatic rupture of the descending thoracic aorta with
      development of a giant pseudoaneurysm.

PMID- 11287525
TI  - The use of mechanical thrombectomy devices in the management of acute peripheral
      arterial occlusive disease.
AB  - A number of percutaneous mechanical thrombectomy devices are currently being used
      or undergoing clinical evaluation for the treatment of acute and chronic limb
      threatening ischemia. Preliminary studies on the safety, efficacy, and device
      limitations have spurred an interest in percutaneous techniques for thrombus
      debulking as stand-alone therapy or an adjunct to pharmacologic thrombolysis. The
      devices have various mechanisms or combinations of mechanisms to optimize
      thrombus removal. Efficacy of thrombus removal is balanced by the propensity for
      vessel wall damage and distal embolization, especially for wall-contact devices
      (Arrow-Trerotola device and Cragg and Castaneda brushes). Initial experience in
      hemodialysis graft occlusion has subsequently moved on to peripheral arterial
      occlusions. Although the U.S. Food and Drug Administration has approved eight
      mechanical thrombectomy devices (MTDs) for use in thrombosed hemodialysis grafts,
      only the AngioJet LF140 is currently approved for use in peripheral arterial
      occlusive disease. Nevertheless, numerous clinical articles and abstracts have
      reported the "off-label" use of MTDs in the management of limb-threatening
      ischemia. A description of the eight MTDs and a review of the current literature
      on use of MTDs for acute peripheral arterial occlusive disease are provided.

PMID- 11287526
TI  - Rheolytic thrombectomy in the management of acute and subacute limb-threatening
      ischemia.
AB  - PURPOSE: To evaluate the use of a percutaneous mechanical thrombectomy (PMT)
      catheter (AngioJet) as an initial treatment for acute (<2 weeks) and subacute (2
      weeks to 4 months) arterial occlusion of the limbs. MATERIALS AND METHODS: A
      total of 86 (acute, n = 65; subacute, n = 21) patients were available for
      retrospective analysis, averaging 65 +/- 14 years of age. Outcomes assessed
      include initial angiographic success (failure = less than 50% luminal restoration
      [LR]; partial success = 50%-95% LR; success = more than 95% LR), pre- and
      postprocedural ankle-brachial index (ABI), device-related and systemic
      complications, 1-month amputation, mortality, and short-term patency. RESULTS:
      Angiographic success was evaluated in 83 of 86 patients (guide wire unable to
      traverse lesion in three patients). The procedure failed in 13 of 83 (15.6%)
      patients, partial success was seen in 19 of 83 patients (22.9%), and successful
      recanalization was noted in 51 of 83 patients (61.4%). Adjunctive thrombolysis
      was used in 50 of 86 patients (58%). However, thrombolysis resulted in
      angiographic improvement at the site of PMT in only seven of 50 of these patients
      (14%). Adjunctive thrombolysis was uniformly unsuccessful in patients in whom
      initial PMT failed. The median increase in ABI was 0.64 (95% CI: 0.43-0.81).
      Success was more likely in the setting of in situ thrombosis, with 61 of 68 (90%)
      procedures successful, compared to embolic occlusions, with nine of 15 (60%)
      procedures successful (P =.011). Angiographic outcome was not dependent on the
      duration of occlusion (acute, 51 of 62; subacute, 19 of 21; P =.35) or the
      conduit type (graft, 28 of 31; native vessel, 42 of 52; P =.35). An underlying
      stenosis was identified in 53 of the 70 patients (75.7%) with a successful PMT,
      and 51 of these 53 unmasked lesions were successfully treated. Follow-up data
      were available in 56 patients for patency assessment at a median of 3.9 months
      (range, 0.1-28.5 months). Patency at 6 months was 79% (95% CI: 65-92). Systemic
      complications occurred in 16.3% of patients, local complications were noted in
      18.6%, and 1-month amputation and mortality rates were 11.6% and 9.3%,
      respectively. CONCLUSION: PMT offers the potential to rapidly reestablish flow to
      an ischemic extremity and may be the only available treatment option in patients
      at high risk for open surgery or with contraindications to pharmacologic
      thrombolysis.

PMID- 11287527
TI  - Transcatheter intraarterial infusion of rt-PA for acute lower limb ischemia:
      results and complications.
AB  - PURPOSE: To determine the success and complication rates of intraarterial
      recombinant tissue-type plasminogen activator (rt-PA) infusion for the treatment
      of acute lower extremity artery and bypass graft occlusions. MATERIALS AND
      METHODS: The results of 74 limbs in 70 patients (mean age, 66 y) treated with
      catheter-directed rt-PA infusion for the treatment of acute lower extremity
      ischemia were retrospectively evaluated. The group included 42 bypass grafts and
      32 native arteries. All limbs were viable at presentation. The mean duration of
      symptoms was 11.9 days. rt-PA was infused for a mean of 27.9 hours for a mean
      total dose of 38.7 mg. Initial infusion rates of 3-6 mg/h were lowered to a
      preferred rate of 1.5 mg/h. Thrombolytic success was defined as 95% thrombolysis
      of an occluded segment with return of antegrade flow. Major bleeding
      complications were defined as any hemorrhagic event leading to surgery, extended
      or unexpected hospitalization, transfusion, death, intracranial hemorrhage, or a
      decrease in hemoglobin of 5 g/dL or in hematocrit of 15%. Thirty-day mortality
      and amputation rates were calculated. Patient characteristics and infusion
      parameters were evaluated as to whether they contributed to thrombolytic success
      or major bleeding events. RESULTS: Thrombolytic success was achieved in 64 limbs
      (86%). Major bleeding complications occurred in 33 (47%) patients. In 22 of these
      patients, bleeding occurred at a vascular puncture site, whereas remote bleeding
      occurred in seven patients. Remote bleeding complications included two
      retroperitoneal hematomas, two rectus sheath hematomas, one lower
      gastrointestinal hemorrhage, one episode of hemoptysis, and one dehiscence of a
      femoral-popliteal bypass graft revision. No parameters were found to be
      predictive of thrombolytic success, whereas a negative history of smoking,
      increasing duration of infusion, and a low preprocedural ankle-brachial index
      (ABI) were found to be associated with major hemorrhagic events. Four patients
      (6%) underwent amputation and one patient (1%) died, resulting in a 30-day
      amputation-free survival rate of 93%. CONCLUSION: Catheter-directed rt-PA
      infusion is effective in achieving thrombolysis. Despite a significant number of
      bleeding complications, 30-day mortality and amputation rates were favorable.
      Nonetheless, complication rates related to bleeding were not trivial and further
      evaluation with use of variable dosing regimens is indicated.

PMID- 11287528
TI  - A randomized, prospective evaluation of the Tesio, Ash split, and Opti-flow
      hemodialysis catheters.
AB  - PURPOSE: A randomized, prospective evaluation of three high-flow hemodialysis
      catheters. MATERIALS AND METHODS: Ninety-four patients were randomly assigned 113
      Tesio, Ash split, and Opti-flow catheters from December 1998 through June 1999.
      Insertion times, procedural complications, and ease of insertion were recorded.
      Mean catheter flow rates were recorded at first dialysis, 30 days, and 90 days.
      Patency, catheter survival, and catheter-related infections were evaluated.
      RESULTS: Thirty-eight Ash split, 39 Opti-flow, and 36 Tesio catheters were
      placed. Tesio mean insertion time (41.5 min) was significantly longer than Ash
      split (29.4 min) or Opti-flow (29.6 min) (P =.004). There were four complications
      related to Tesio catheters (three cases of pericatheter bleeding, one air
      embolism), one related to an Opti-flow catheter (pericatheter bleeding), and zero
      related to Ash split catheters. Opti-flow and Ash split catheters were
      significantly easier to insert than Tesio catheters (P =.041). Mean flow rates
      were not significantly different among the catheters initially (P =.112), at 30
      days (P =.281), or at 90 days (P =.112). Catheter-related infection rates per 100
      catheter days were 0.12 for Ash split, 0.35 for Opti-flow, and 0.14 for TESIO:
      Median catheter survival was 302 days for Ash split, 176 days for Opti-flow, and
      228 days for TESIO: CONCLUSIONS: Opti-Flow and Ash split catheters were faster
      and easier to place than Tesio catheters. There was no difference in hemodialysis
      flow rates or catheter survival.

PMID- 11287529
TI  - Ovarian function after uterine artery embolization for leiomyomata: assessment
      with use of serum follicle stimulating hormone assay.
AB  - PURPOSE: To determine if uterine artery embolization (UAE) for leiomyomata causes
      a change in ovarian function as measured by serial basal follicle stimulating
      hormone (FSH) assay. MATERIALS AND METHODS: Sixty-three patients undergoing UAE
      for symptomatic leiomyomata had blood samples obtained on day 3 of a menstrual
      cycle before UAE and on day 3 during menstrual cycles 3 and 6 months after
      treatment. Analysis of variance was used to detect differences in FSH levels
      among age groups at each interval. Repeated measures analysis of variance was
      used to determine if individual mean change occurred for the group as a whole and
      for each age group. Onset of new menopausal symptoms was compared between groups
      with use of the chi(2) test. RESULTS: There was no significant change in basal
      FSH levels for the group as a whole (P =.16), but there was a statistically
      significant difference when age groups were compared (P =.03). Individual change
      of >2 SD from baseline mean FSH level occurred at 6 months in seven patients, all
      45-50 years of age. Four of these patients (15% of patients over age 44) had FSH
      levels increase to more than 20 IU/L. chi(2) analysis did not reveal any
      difference among the groups studied in the onset of menopausal symptoms.
      CONCLUSIONS: Most patients had no change in ovarian function as measured by basal
      FSH after UAE. For patients aged 45 or older, there is approximately a 15% chance
      of an increase in basal FSH into the perimenopausal range.

PMID- 11287530
TI  - Fibroid calcification after uterine artery embolization: ultrasonographic
      appearance and pathology.
AB  - PURPOSE: To describe the ultrasonographic (US) appearance of fibroid
      calcification occurring after uterine artery embolization (UAE) and discuss its
      etiology and pathology. MATERIALS AND METHODS: Twenty-seven of a total of 38
      patients were followed up clinically and with duplex US for longer than 6 months
      after UAE for uterine fibroids. At US, changes in uterine size, fibroid
      vascularity, and morphology have been recorded. Pathologic studies were performed
      by one of the authors on resected specimens from a different cohort of patients,
      at intervals ranging from 4 months to 1 year after UAE. RESULTS: Twenty patients
      reported complete resolution of symptoms. In 16 of these, a reduction in fibroid
      volume of 70%-85% was recorded and, at US, the development of a peripheral
      hyperechoic rim around an increasingly hypoechoic fibroid was noted. Computed
      tomography in two patients revealed it to be a rim of calcium. Histologic studies
      in a different cohort of patients who had undergone hysterectomy at variable
      intervals after UAE demonstrated early aggregation of polyvinyl alcohol (PVA)
      particles, an intermediate giant cell inflammatory reaction, and calcification in
      the periphery of the infarcted fibroid at 6-12 months. CONCLUSION: Calcification
      is the end stage of hyaline degeneration. However, its peripheral location is
      unlike that of natural fibroid involution and hyaline necrosis. Pathologic
      studies in resected human fibroids after embolization suggest that its
      development is the end result of aggregation of PVA particles in peripheral
      fibroid arteries.

PMID- 11287531
TI  - CPT coding by interventional radiologists: accuracy and implications.
AB  - PURPOSE: To evaluate the accuracy of Current Procedural Terminology (CPT) coding
      for interventional radiology services when coding is performed by the operating
      physician. MATERIALS AND METHODS: Coding data for 1,174 interventional radiology
      encounters in 736 patients were analyzed for appropriate use of CPT codes.
      Physician operators initially assigned provisional codes. Formal coding for
      billing purposes was performed at a later date by one of two experienced
      interventional radiology physician coders. Initial operator coding errors and
      associated relative value unit (RVU) impact were analyzed. The coding patterns of
      experienced physician coders were compared with those of the other
      interventionalists. RESULTS: Only 82% of encounters were initially coded
      correctly, with a small net tendency toward undercoding. The overall net RVU
      impact of errors was only -1.2%, with the effects of undercoding outweighing
      those of overcoding. More complex cases (> or =4 CPT codes) were much more likely
      to be coded erroneously than less complex cases (24% vs 14%, P <.001).
      Experienced physician coders committed significantly fewer errors than other
      physicians (10% vs 25%, P <.001), but there was a similar minimal net RVU impact
      of errors (-1.1% vs -1.4%, P =.198). CONCLUSION: Although initial physician
      coding errors for interventional radiology procedures are common, the net RVU
      impact is minimal. The accuracy of experienced physician coders is significantly
      higher than that for other interventionalists. Because of the regulatory
      consequences of coding inaccuracies, practices should establish quality
      improvement systems to minimize errors and use the skills of experienced
      individuals in their coding processes.

PMID- 11287532
TI  - Percutaneous radiofrequency ablation of liver tumors with the LeVeen probe: is
      roll-off predictive of response?
AB  - PURPOSE: The LeVeen radiofrequency (RF) probe uses roll-off of electrical
      impedance as the endpoint for RF cautery of hepatic tumors. The purpose of this
      study is to determine the relation of roll-off to local control of hepatic
      tumors. MATERIALS AND METHODS: Twenty hepatic tumors, including 10 hepatomas and
      10 metastases, were treated. Lesions ranged from 1.4 cm to 6.0 cm in diameter; 13
      (57%) were smaller than 3.0 cm. Each lesion was ablated with use of the LeVeen 15
      gauge RF needle according to the manufacturer's protocol. Five patients underwent
      chemoembolization the day before. Patients were followed up with contrast
      enhanced computed tomography or magnetic resonance imaging at 1 month and every 3
      months thereafter. RESULTS: Among the 20 lesions, roll-off was achieved at all
      burn locations in 11 (55%), no burn locations in eight (40%), and two of three
      burn locations in one (5%). Roll-off was observed in all patients who had
      undergone chemoembolization the day before. Six local recurrences occurred, five
      after RF ablation without roll-off and one after RF ablation with roll-off.
      According to life-table analysis, the local recurrence rate at 6 months without
      roll-off was 43% and with roll-off was 15% (P =.024; OR = 8.3; 95% CI = 0.93-66).
      CONCLUSION: Roll-off is a significant predictor of local control after RF
      ablation. Strategies to enhance roll-off, such as concurrent embolization, may be
      important to optimize the therapeutic effect of this device.

PMID- 11287533
TI  - Prospective comparison of MR phase-contrast velocimetry with intravascular
      doppler US during infrainguinal artery angioplasty.
AB  - PURPOSE: To evaluate the accuracy of magnetic resonance (MR) velocimetry for
      quantitative assessment of stenosis in patients undergoing percutaneous
      transluminal angioplasty (PTA). MATERIALS AND METHODS: Thirty patients underwent
      PTA of the infrainguinal region. To assess hemodynamic parameters of lesions, MR
      phase-contrast velocimetry with a circular-polarized extremity receiver coil and
      a cardiac gated gradient echo sequence was conducted before and 1 day after PTA.
      Additionally, all lesions were examined by means of intravascular Doppler flow
      measurements (0.018-inch wire, 12 MHz). From these data, the degree of stenosis
      was calculated and a comparison of MR velocimetry with intravascular Doppler US
      was undertaken. RESULTS: Correlation between calculated grade of stenosis for MR
      velocimetry and intravascular Doppler US was good and significant (r = 0.74; P
      <.001). Calculated luminal stenosis grade were similar for both methods before
      PTA (intravascular Doppler US: 0.62 +/- 0.18, MR velocimetry: 0.54 +/- 0.19; P
      =.17 with paired Student t-test) and after PTA (0.25 +/- 0.23 and 0.3 +/- 0.2,
      respectively; P =.56). CONCLUSION: MR velocimetry results in reliable noninvasive
      in vivo flow measurements and allows accurate assessment of stenosis in a
      clinical setting.

PMID- 11287534
TI  - Delayed complications after esophageal stent placement for treatment of malignant
      esophageal obstructions and esophagorespiratory fistulas.
AB  - PURPOSE: To evaluate delayed complications after esophageal expandable metallic
      stent placement. MATERIALS AND METHODS: From April 1993 to December 1997, 90
      expandable metallic stents were placed in 82 consecutive patients with inoperable
      malignant esophageal obstruction (n = 49) or malignant esophagorespiratory
      fistula (n = 33). Stents used included covered Gianturco-Rosch Z stents (n = 20),
      Wallstents (covered, n = 31; uncovered, n = 13), and Ultraflex stents (covered, n
      = 8; uncovered, n = 10). Patients were followed prospectively and monitored for
      delayed complications, defined as major (hemorrhage, tracheal compression, stent
      migration, perforation or fistula formation, granulomatous obstruction, tumor
      ingrowth and overgrowth, funnel phenomenon, and stent covering disruption) or
      minor (reflux, chest pain, and food impaction). RESULTS: Mean survival was 4.5
      months after stent placement (range, 3 weeks to 26 months). The overall incidence
      of delayed complications was 64.6%, with 17 patients (20.7%) experiencing more
      than one complication. The rates of delayed complications in patients with Z
      stents, Wallstents, and Ultraflex stents were 75.0%, 68.1%, and 44.4%,
      respectively (P <.05). Most complications were life-threatening and occurred more
      frequently when stents were placed in the proximal third of the esophagus,
      compared with more distally (P <.05). Thirteen patients (15.9%) died from
      complications directly related to stent placement. CONCLUSION: Esophageal stent
      placement for malignant obstruction or fistula is associated with a substantial
      incidence of delayed complications.

PMID- 11287535
TI  - Intravascular US-guided direct intrahepatic portacaval shunt with a PTFE-covered
      stent-graft: feasibility study in swine and initial clinical results.
AB  - PURPOSE: To determine the feasibility of the creation of a direct intrahepatic
      inferior vena cava (IVC)-to-portal-vein shunt with puncture guided by a
      transfemorally placed intravascular ultrasound (IVUS) probe and use of a
      polytetrafluoroethylene (PTFE)-covered stent-graft. MATERIALS AND METHODS: In
      five swine, transjugular access was used to perform a direct puncture from the
      IVC to the portal vein with use of a modified Rosch-Uchida Portal Access set
      directed with real-time IVUS (9 MHz) introduced from a transfemoral venous
      approach. The direct intrahepatic portocaval shunt (DIPS) was then created with
      single or overlapping PTFE-covered Palmaz stents placed through a 10-F sheath and
      dilated to a diameter of 8 mm. Follow-up was performed with transhepatic
      portography at 2, 4, and 8 weeks. Animals were killed when shunts occluded or at
      the termination of the study at 8 weeks. Gross and microscopic histologic study
      was performed on sacrificed animals. A similar technique was used to create DIPS
      in five patients with intractable ascites, with follow-up by US and venography.
      RESULTS: All experimental DIPS created in swine were created without
      complications. Portal vein punctures were achieved in four of five swine on the
      first or second pass of the needle. Follow-up transhepatic portography at 2 weeks
      demonstrated occlusion of two shunts, both explained by technical reasons at
      sacrifice. At 4 and 8 weeks, the remaining three shunts were patent on
      portography. Histology showed a thin neointimal lining with no significant tissue
      ingrowth or hyperplasia. Clinically, in five patients, successful puncture of the
      portal vein from the IVC was achieved in one to three passes. Creation of DIPS
      led to a reduction of mean portosystemic gradient from 18-29 mm Hg (mean, 24 mm
      Hg) to 9-10 mm Hg (mean, 9 mm Hg). One patient died of liver failure 2 days after
      creation of DIPS. The other four patients were doing well 2-15 months (mean, 8
      months) after the procedure, with patency confirmed by US and venography.
      CONCLUSION: Creation of DIPS is technically feasible, and the direct IVC-to
      portal-vein puncture can be done accurately with real-time IVUS guidance. Further
      studies and longer follow-up are necessary to determine if the short length of
      the PTFE-covered stent-graft and avoidance of the hepatic vein will increase the
      long-term patency compared to standard transjugular intrahepatic portosystemic
      shunt creation.

PMID- 11287537
TI  - Use of an Amplatz Goose Neck snare as a target for collateral neck vein dialysis
      catheter placement.
AB  - The authors describe a technique for insertion of a hemodialysis catheter when
      the usual large neck veins are difficult to access. The essence of the procedure
      is the use of the Amplatz Goose Neck snare as a fluoroscopic target. The snare is
      used in its conventional mode to grasp the introduction wire. The dialysis line
      then can be placed in its usual fashion.

PMID- 11287536
TI  - Evaluation of local abciximab delivery from the surface of a polymer-coated
      covered stent: in vivo canine studies.
AB  - PURPOSE: To determine the in vitro feasibility of abciximab absorption and
      elution from a polymer-coated, silicone-covered stent, and to determine the in
      vivo effect of local delivery of abciximab concerning endothelialization of a
      polymer-coated, silicone-covered stent in a canine model. MATERIALS AND METHODS:
      Six polymer-coated, silicone-lined Wallstents were soaked in 2 mg/mL of
      concentrated solution of I131-labeled abciximab for a period as long as 48 hours.
      Quantification of abciximab absorption was determined by photon emission. Six
      maximally drug-loaded devices were then washed continuously with normal saline
      with use of a pustule pump apparatus. The quantity of residual abciximab was
      determined by photon emission for a period as long as 16 days. Eight similar
      devices (as described previously) were then implanted within the iliac arteries
      of four adult canines. Devices were identical except that four of eight were
      maximally loaded with abciximab. For each animal, one control implant was placed
      in the right iliac artery and one experimental implant (drug loaded) was placed
      in the left iliac artery, via right carotid cutdown. Animals were allowed to
      recover and no chronic medications were given. After an interval of 6 weeks, the
      animals were killed. Implants were isolated and perfused with 10% buffered
      formalin at a pressure of approximately 100 mm Hg for a period of 1 hour. Each
      implant was encased in methacrylate, sectioned into six equal segments, ground
      and polished, and stained with hematoxylin and eosin. Each slide was projected on
      a screen and the thickness of the neointima quantified. The mean neointima was
      determined for control and experimental groups, and compared for a potential
      significant difference with a Student t test. RESULTS: Mean absorption of
      abciximab was 21.53 microg +/- 2.99 per device. Devices were fully saturated at
      24 hours. Forty percent was absorbed at 1 hour, and 60% and 80% were absorbed at
      4 hours and 12 hours, respectively. Regarding elution, 30% of abciximab was
      washed out after 1 hour. There was a gradual elution of the drug to 16 days, with
      approximately 40% remaining at the end of the term. Mean neointimal thickness was
      995 microm +/- 597 for the experimental group and 1,738 microm +/- 1,042 for the
      control group. The difference was significant (P <.05). CONCLUSIONS: Absorption
      and elution of abciximab from the surface of a covered stent is feasible. Local
      delivery of abciximab from the surface of this covered stent reduced the
      thickness of endothelial lining in the canine iliac artery compared to control.

PMID- 11287538
TI  - Use of a catheter with a large side hole for selective catheterization of the
      inferior phrenic artery.
AB  - The authors report the use of a catheter with a large side hole in the
      catheterization of the right inferior phrenic artery (IPA) arising from the
      proximal portion of the celiac trunk. A 5-F catheter with a side hole on either
      the top or the right side of the superior portion near the tip was used in five
      patients with hepatocellular carcinoma fed by the right IPA, which could not be
      selected by a conventional coaxial technique. In all patients, a 3-F
      microcatheter was successfully advanced into the right IPA through the side hole
      of this catheter introduced into the celiac artery or the common hepatic artery.

PMID- 11287539
TI  - Balloon dacryocystoplasty: results and factors influencing outcome in 350
      patients.
AB  - PURPOSE: To evaluate the initial and long-term results of balloon
      dacryocystoplasty in the treatment of epiphora caused by obstruction of the
      lacrimal system with analysis of the procedure's favorable effects. MATERIALS AND
      METHODS: Four hundred thirty eyes of 350 patients with obstructions of the
      lacrimal system were enrolled. Dacryocystoplasty was performed with use of a
      balloon catheter and a ball-tipped guide wire. The lesions were categorized
      according to cause, severity, site of the obstruction, and diameter and inflation
      time of the balloon. The technical success, initial success (improvement of
      symptoms after 1 week), and long-term patency rates were calculated. These rates
      in each group were compared with the chi(2) test and the Kaplan-Meier method.
      RESULTS: The overall technical success rate was 95.3%. The overall initial
      success rate was 57.4%. There was no significant complication except for mild
      epistaxis in 12%. The 2-month, 1-year, and 5-year patency rates were 48.2%,
      39.4%, and 36.9%, respectively. Initial success was influenced by the severity (P
      =.014) and the site (P <.001) of the obstruction, and the diameter of the balloon
      (P =.047). Long-term patency was affected by the site of the obstruction (P
      <.001) and the balloon inflation time (P <.001). Among the 183 initially
      ineffective and 88 recurrent cases, 62 underwent repeat balloon
      dacryocystoplasty, and the initial success rate was 38.7%. CONCLUSIONS: The
      initial success rate of balloon dacryocystoplasty is relatively low. However,
      long-term patency can be expected in cases with initial success. Some additional
      factors also should be considered for better results.

PMID- 11287540
TI  - Value of three-dimensional US for optimizing guidance for ablating focal liver
      tumors.
AB  - PURPOSE: To determine if three-dimensional ultrasound (3D US), by nature of its
      ability to simultaneously evaluate structures in three orthogonal planes and to
      study relationships of devices to tumor(s) and surrounding anatomic structures
      from any desired orientation, adds significant additional information to real
      time 2D US used for placement of devices for ablation of focal liver tumors.
      MATERIALS AND METHODS: Sixteen patients underwent focal ablation of 23 liver
      tumors during two intraoperative cryoablation (CA) procedures, three
      intraoperative radiofrequency ablation (RFA) procedures, 11 percutaneous ethanol
      injections (PEI) procedures, and six percutaneous RFA procedures. After
      satisfactory placement of the ablative device(s) with 2D US guidance, 3D US was
      used to reevaluate adequacy to device position. Information added by 3D US and
      resultant alterations in device deployment were tabulated. RESULTS: 3D US added
      information in 20 of 22 (91%) procedures and caused the operator to readjust the
      number or position of ablative devices in 10 of 22 (45%) of procedures.
      Specifically, 3D US improved visualization and confident localization of devices
      in 13 of 22 (59%) procedures, detected unacceptable device placement in 10 of 22
      (45%), and determined that 2D US had incorrectly predicted device orientation to
      a tumor in three of 22 (14%). CONCLUSIONS: Compared to conventional 2D US, 3D US
      provides additional relationship information for improved placement and optimal
      distribution of ablative agents for treatment of focal liver malignancy.

PMID- 11287541
TI  - Type B aortic dissection complicating renal artery angioplasty and stent
      placement.
AB  - Percutaneous renal artery stent placement has been demonstrated to improve blood
      pressure control and stabilize renal function in patients with atherosclerotic
      renal artery disease. However, this procedure is not without risk of significant
      morbidity, and its effectiveness, as compared to alternative treatments, has not
      been adequately established. The authors report a case of acute type B aortic
      dissection complicating renal artery stent placement. The authors postulate that
      an intimal disruption occurred during initial balloon angioplasty, and that
      repeated application of radial, shear, and torque forces during stent placement
      may have extended the injury. The diagnosis of acute aortic dissection should be
      considered in patients with suggestive symptoms immediately after stent
      placement.

PMID- 11287542
TI  - Tuberculous aneurysm of the aorta presenting with uncontrolled hypertension.
AB  - Mycotic aneurysm secondary to tuberculous infection of the aorta is a rare entity
      with less than 50 cases having been described in the literature. Clinical
      presentation is usually a consequence of the aneurysm, including pain, palpable
      mass, or hypovolemia secondary to leak. Definitive treatment is surgical, with
      nearly 30 documented successful cases. The authors present a case of tuberculous
      aortitis with mycotic aneurysms that presented with uncontrolled hypertension and
      occlusion of the right renal artery that underwent successful surgical repair.

PMID- 11287543
TI  - Percutaneous treatment of a pancreatic fistula after pancreaticoduodenectomy.
AB  - Breakdown of the pancreaticojejunal anastomosis after a Whipple procedure is
      reported to occur in as many as 15% of cases. Intraoperative placement of a drain
      adjacent to the anastomosis is performed to allow the creation of a controlled
      pancreaticocutaneous fistula in the event of an anastomotic disruption. The
      authors present a case of successful percutaneous treatment of a disrupted
      pancreaticojejunal anastomosis. This was achieved with use of the resulting
      pancreaticocutaneous fistula for access to restore internal drainage, followed by
      fistula occlusion with use of gelatin pledgets.

PMID- 11287544
TI  - Ehlers-Danlos syndrome mimicking mesenteric vasculitis: therapy, then diagnosis.
AB  - The etiology of acute intraabdominal bleeding is often unclear at the time
      emergent arteriography is performed. During localization and embolization, the
      arteriogram may suggest the diagnosis of vasculitis. However, controlling the
      bleeding remains the priority. Connective tissue diseases such as Ehlers-Danlos
      syndrome (EDS) may also cause bleeding and mimic vasculitis and must be included
      in the differential diagnosis. We present such a case in which the initial
      findings were misleading.

PMID- 11287545
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 1:
      Hughes-Stovin syndrome.

PMID- 11287546
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 2: Left
      hepatic arterioportal fistula.
AB  - A 65-year-old man with cryptogenic cirrhosis initially underwent transjugular
      intrahepatic portosystemic shunt (TIPS) creation for variceal bleeding. For the
      following 16 months, variceal bleeding and intractable ascites persisted despite
      TIPS revision with variceal embolization. A surgical distal splenorenal shunt was
      then created, but, although there was initial improvement, intractable ascites
      recurred. At presentation at a different hospital, the patient gave a history of
      dyspnea on exertion and orthopnea. Physical examination demonstrated a distended
      abdomen, consistent with severe ascites, a large right pleural effusion, and
      bilateral peripheral edema.

PMID- 11287547
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 3:
      Right middle adrenal artery aneurysm.

PMID- 11287548
TI  - SCVIR annual meeting film panel session: diagnosis and discussion of case 4:
      Infected aortic aneurysm.

PMID- 11287549
TI  - Selective transcatheter platelet infusion for gastrointestinal bleeding after
      failed embolization with resistant thrombocytopenia.

PMID- 11287550
TI  - Jugular vein placement of a small-caliber dual-lumen catheter in patients with
      chronic renal insufficiency or chronic renal failure.

PMID- 11287551
TI  - Quintuple deglycosylation mutant of simian immunodeficiency virus SIVmac239 in
      rhesus macaques: robust primary replication, tightly contained chronic infection,
      and elicitation of potent immunity against the parental wild-type strain.
AB  - We previously generated a mutant of simian immunodeficiency virus (SIV) lacking 5
      of a total of 22 N-glycans in its external envelope protein gp120 with no
      impairment in viral replication capability and infectivity in tissue culture
      cells. Here, we infected rhesus macaques with this mutant and found that it also
      replicated robustly in the acute phase but was tightly, though not completely,
      contained in the chronic phase. Thus, a critical requirement for the N-glycans
      for the full extent of chronic infection was demonstrated. No evidence indicating
      reversion to a wild type was obtained during the observation period of more than
      40 weeks. Monkeys infected with the mutant were found to tolerate a challenge
      infection with wild-type SIV very well. Analyses of host responses following
      challenge revealed no neutralizing antibodies against the challenge virus but
      strong secondary responses of cytotoxic T lymphocytes against multiple antigens,
      including Gag-Pol, Nef, and Env. Thus, the quintuple deglycosylation mutant
      appeared to represent a novel class of SIV live attenuated vaccine.

PMID- 11287553
TI  - West Nile virus recombinant DNA vaccine protects mouse and horse from virus
      challenge and expresses in vitro a noninfectious recombinant antigen that can be
      used in enzyme-linked immunosorbent assays.
AB  - Introduction of West Nile (WN) virus into the United States in 1999 created major
      human and animal health concerns. Currently, no human or veterinary vaccine is
      available to prevent WN viral infection, and mosquito control is the only
      practical strategy to combat the spread of disease. Starting with a previously
      designed eukaryotic expression vector, we constructed a recombinant plasmid
      (pCBWN) that expressed the WN virus prM and E proteins. A single intramuscular
      injection of pCBWN DNA induced protective immunity, preventing WN virus infection
      in mice and horses. Recombinant plasmid-transformed COS-1 cells expressed and
      secreted high levels of WN virus prM and E proteins into the culture medium. The
      medium was treated with polyethylene glycol to concentrate proteins. The
      resultant, containing high-titered recombinant WN virus antigen, proved to be an
      excellent alternative to the more traditional suckling-mouse brain WN virus
      antigen used in the immunoglobulin M (IgM) antibody-capture and indirect IgG
      enzyme-linked immunosorbent assays. This recombinant antigen has great potential
      to become the antigen of choice and will facilitate the standardization of
      reagents and implementation of WN virus surveillance in the United States and
      elsewhere.

PMID- 11287552
TI  - Reovirus binding to cell surface sialic acid potentiates virus-induced apoptosis.
AB  - Reovirus induces apoptosis in cultured cells and in vivo. Genetic studies
      indicate that the efficiency with which reovirus strains induce apoptosis is
      determined by the viral S1 gene, which encodes attachment protein sigma1.
      However, the biochemical properties of sigma1 that influence apoptosis induction
      are unknown. To determine whether the capacity of sigma1 to bind cell surface
      sialic acid determines the magnitude of the apoptotic response, we used isogenic
      reovirus mutants that differ in the capacity to engage sialic acid. We found that
      T3SA+, a virus capable of binding sialic acid, induces high levels of apoptosis
      in both HeLa cells and L cells. In contrast, non-sialic-acid-binding strain T3SA-
      induces little or no apoptosis in these cell types. Differences in the capacity
      of T3SA- and T3SA+ to induce apoptosis are not due to differences in viral
      protein synthesis or production of viral progeny. Removal of cell surface sialic
      acid with neuraminidase abolishes the capacity of T3SA+ to induce apoptosis.
      Similarly, incubation of T3SA+ with sialyllactose, a trisaccharide comprised of
      lactose and sialic acid, blocks apoptosis. These findings demonstrate that
      reovirus binding to cell surface sialic acid is a critical requirement for the
      efficient induction of apoptosis and suggest that virus receptor utilization
      plays an important role in regulating cell death.

PMID- 11287554
TI  - Regulation of viral intermediate gene expression by the vaccinia virus B1 protein
      kinase.
AB  - The B1 gene of vaccinia virus encodes a serine/threonine protein kinase that is
      expressed early after infection. Under nonpermissive conditions, temperature
      sensitive mutants (ts2 and ts25) that map to B1 fail to efficiently replicate
      viral DNA. Our goal was to extend studies on the function of B1 by determining if
      the kinase is required for intermediate or late gene expression, two events that
      ordinarily depend on viral DNA replication. First, we established that early
      viral gene expression occurred at the nonpermissive temperature. By using a
      transfection procedure that circumvents the viral DNA replication requirement, we
      found that reporter genes regulated by an intermediate promoter were transcribed
      only under conditions permissive for expression of active B1. To assay late gene
      expression, the T7 RNA polymerase gene was inserted into the genome of ts25 to
      form ts25/T7. A DNA replication-independent late gene transcription system was
      established by cotransfecting plasmids containing T7 promoter-driven late gene
      transcription factors and a late promoter reporter gene into ts25/T7-infected
      cells. Late genes, unlike intermediate genes, were expressed at the nonpermissive
      temperature. Last, we showed that overexpression of B1 stimulated intermediate
      but inhibited late gene expression in cells infected with wild-type virus.

PMID- 11287555
TI  - Construction and in vitro properties of a series of attenuated simian
      immunodeficiency viruses with all accessory genes deleted.
AB  - We have generated simplified simian immunodeficiency virus (SIV) constructs
      lacking the nef, vpr, vpx, vif, tat, and rev genes (Delta6 viruses). To
      accomplish this, we began with an infectious molecular clone of SIV, i.e.
      SIVmac239, and replaced the deleted segments with three alternate elements: (i) a
      constitutive transport element (CTE) derived from simian retrovirus type 1 to
      replace the Rev/Rev-responsive element (RRE) posttranscriptional regulation
      system, (ii) a chimeric SIV long terminal repeat (LTR) containing a
      cytomegalovirus (CMV) promoter to augment transcription and virus production, and
      (iii) an internal ribosome entry site (IRES) upstream of the env gene to ensure
      expression of envelope proteins. This simplified construct (Delta6CCI)
      efficiently produced all viral structural proteins, and mature virions possessed
      morphology typical of wild-type virus. It was also observed that deletion of the
      six accessory genes dramatically affected both the specificity and efficiency of
      packaging of SIV genomic RNA into virions. However, the presence of both the CTE
      and the chimeric CMV promoter increased the specificity of viral genomic RNA
      packaging, while the presence of the IRES augmented packaging efficiency. The
      Delta6CCI virus was extremely attenuated in replication capacity yet retained
      infectiousness for CEMx174 and MT4 cells. We also generated constructs that
      retained either the rev gene or both the rev and vif genes and showed that these
      viruses, when complemented by the CMV promoter, i.e., Delta5-CMV and Delta4-CMV,
      were able to replicate in MT4 cells with moderate and high-level efficiency,
      respectively. Long-term culture of each of these constructs over 6 months
      revealed no potential for reversion. We hope to shortly evaluate these simplified
      constructs in rhesus macaques to determine their long-term safety as well as
      ability to induce protective immune responsiveness as proviral DNA vaccines.

PMID- 11287556
TI  - The SH integral membrane protein of the paramyxovirus simian virus 5 is required
      to block apoptosis in MDBK cells.
AB  - In some cell types the paramyxovirus simian virus 5 (SV5) causes little
      cytopathic effect (CPE) and infection continues productively for long periods of
      time; e.g., SV5 can be produced from MDBK cells for up to 40 days with little
      CPE. SV5 differs from most paramyxoviruses in that it encodes a small (44-amino
      acid) hydrophobic integral membrane protein (SH). When MDBK cells were infected
      with a recombinant SV5 containing a deletion of the SH gene (rSV5DeltaSH), the
      MDBK cells exhibited an increase in CPE compared to cells infected with wild-type
      SV5 (recovered from cDNA; rSV5). The increased CPE correlated with an increase in
      apoptosis in rSV5DeltaSH-infected cells over mock-infected and rSV5-infected
      cells when assayed for annexin V binding, DNA content (propidium iodide
      staining), and DNA fragmentation (terminal deoxynucleotidyltransferase-mediated
      dUTP-biotin nick end labeling assay). In rSV5DeltaSH-infected MDBK cells an
      increase in caspase-2 and caspase-3 activities was observed. By using peptide
      inhibitors of individual caspases it was found that caspase-2 and caspase-3 were
      activated separately in rSV5DeltaSH-infected cells. Expression of caspase-2 and 
      3 in rSV5DeltaSH-infected MDBK cells appeared not to require STAT1 protein, as
      STAT1 protein could not be detected in SV5-infected MDBK cells. When mutant mice
      homologous for a targeted disruption of STAT1 were used as a model animal system
      and infected with the viruses it was found that rSV5DeltaSH caused less mortality
      than wild-type rSV5, consistent with the notion of clearance of apoptotic cells
      in a host species.

PMID- 11287557
TI  - Adeno-associated virus type 2-mediated gene transfer: altered endocytic
      processing enhances transduction efficiency in murine fibroblasts.
AB  - Adeno-associated virus type 2 (AAV) is a single-stranded-DNA-containing,
      nonpathogenic human parvovirus that is currently in use as a vector for human
      gene therapy. However, the transduction efficiency of AAV vectors in different
      cell and tissue types varies widely. In addition to the lack of expression of the
      viral receptor and coreceptors and the rate-limiting viral second-strand DNA
      synthesis, which have been identified as obstacles to AAV-mediated transduction,
      we have recently demonstrated that impaired intracellular trafficking of AAV
      inhibits high-efficiency transduction of the murine fibroblast cell line, NIH 3T3
      (J. Hansen, K. Qing, H. J. Kwon, C. Mah, and A. Srivastava, J. Virol. 74:992-996,
      2000). In this report, we document that escape of AAV from the endocytic pathway
      in NIH 3T3 cells is not limited but processing within endosomes is impaired
      compared with that observed in the highly permissive human cell line 293. While
      virions were found in both early and late endosomes or lysosomes of infected 293
      cells, they were localized predominantly to the early endosomes in NIH 3T3 cells.
      Moreover, treatment of cells with bafilomycin A1 (Baf), an inhibitor of the
      vacuolar H(+)-ATPase and therefore of endosomal-lysosomal acidification,
      decreased the transduction of 293 cells with a concomitant decrease in nuclear
      trafficking of AAV but had no effect on NIH 3T3 cells. However, after exposure of
      NIH 3T3 cells to hydroxyurea (HU), a compound known to increase AAV-mediated
      transduction in general, virions were detected in late endosomes and lysosomes,
      and these cells became sensitive to Baf-mediated inhibition of transduction.
      Thus, HU treatment overcomes defective endocytic processing of AAV in murine
      fibroblasts. These studies provide insights into the underlying mechanisms of
      intracellular trafficking of AAV in different cell types, which has implications
      in the optimal use of AAV as vectors in human gene therapy.

PMID- 11287559
TI  - Arbovirus of marine mammals: a new alphavirus isolated from the elephant seal
      louse, Lepidophthirus macrorhini.
AB  - A novel alphavirus was isolated from the louse Lepidophthirus macrorhini,
      collected from southern elephant seals, Mirounga leonina, on Macquarie Island,
      Australia. The virus displayed classic alphavirus ultrastructure and appeared to
      be serologically different from known Australasian alphaviruses. Nearly all
      Macquarie Island elephant seals tested had neutralizing antibodies against the
      virus, but no virus-associated pathology has been identified. Antarctic Division
      personnel who have worked extensively with elephant seals showed no serological
      evidence of exposure to the virus. Sequence analysis illustrated that the
      southern elephant seal (SES) virus segregates with the Semliki Forest group of
      Australasian alphaviruses. Phylogenetic analysis of known alphaviruses suggests
      that alphaviruses might be grouped according to their enzootic vertebrate host
      class. The SES virus represents the first arbovirus of marine mammals and
      illustrates that alphaviruses can inhabit Antarctica and that alphaviruses can be
      transmitted by lice.

PMID- 11287558
TI  - Infection of the CD45RA+ (naive) subset of peripheral CD8+ lymphocytes by human
      immunodeficiency virus type 1 in vivo.
AB  - To investigate the mechanism and functional significance of infection of CD8+
      lymphocytes by human immunodeficiency virus type 1 (HIV-1) in vivo, we determined
      frequencies of infection, proviral conformation, and genetic relationships
      between HIV-1 variants infecting naive (CD45RA+) and memory (CD45RO+) peripheral
      blood CD4+ and CD8+ lymphocytes. Infection of CD3+ CD8+ CD45RA+ cells was
      detected in 9 of 16 study subjects at frequencies ranging from 30 to 1,400
      proviral copies/10(6) cells, more frequently than CD3+ CD8+ lymphocytes
      expressing the RO isoform of CD45 (n = 2, 70 and 260 copies /10(6) cells). In
      agreement with previous studies, there was no evidence for a similar preferential
      infection of CD4+ naive lymphocytes. Proviral sequences in both CD4+ and CD8+
      lymphocyte subsets were complete, as assessed by quantitation using primers from
      the long terminal repeat region spanning the tRNA primer binding site. In six of
      the seven study subjects investigated, variants infecting CD8+ lymphocytes were
      partially or completely genetically distinct in the V3 region from those
      recovered from CD4+ lymphocytes and showed a greater degree of
      compartmentalization than observed between naive and memory subsets of CD4+
      lymphocytes. In two study subjects, arginine substitutions at position 306,
      associated with use of the chemokine coreceptor CXCR4, were preferentially found
      in CD4 lymphocytes. These population differences may have originated through
      different times of infection rather than necessarily indicating a difference in
      their biological properties. The preferential distribution of HIV-1 in naive CD8+
      lymphocytes indeed suggests that infection occurred early in T-lymphocyte
      ontogeny, such as during maturation in the thymus. Destruction of cells destined
      to become CD8+ lymphocytes may be a major factor in the decline in CD8+
      lymphocyte frequencies and function on disease progression and may contribute
      directly to the observed immunodeficiency in AIDS.

PMID- 11287560
TI  - Recombinant human parvovirus B19 vectors: erythrocyte P antigen is necessary but
      not sufficient for successful transduction of human hematopoietic cells.
AB  - The blood group P antigen, known to be abundantly expressed on erythroid cells,
      has been reported to be the cellular receptor for parvovirus B19. We have
      described the development of recombinant parvovirus B19 vectors with which high
      efficiency, erythroid lineage-restricted transduction can be achieved (S.
      Ponnazhagan, K. A. Weigel, S. P. Raikwar, P. Mukherjee, M. C. Yoder, and A.
      Srivastava, J. Virol. 72:5224-5230, 1998). However, since a low-level
      transduction of nonerythroid cells could also be detected and since P antigen is
      expressed in nonerythroid cells, we reevaluated the role of P antigen in the
      viral binding and entry into cells. Cell surface expression analyses revealed
      that approximately 75% of primary human bone marrow mononuclear erythroid cells
      and approximately 31% of cells in the nonerythroid population were positive for P
      antigen. Two human erythroleukemia cell lines, HEL and K562, and a human
      promyelocytic leukemia cell line, HL-60, were also examined for P antigen
      expression and binding and entry of the vector. HEL and K562 cells showed
      intermediate levels, whereas HL-60 cells demonstrated high levels of expression
      of P antigen. However, the efficiency of vector binding to these cells did not
      correlate with P antigen expression. Moreover, despite P antigen positivity and
      efficient viral binding, HEL, K562, and HL-60 cells could not be transduced with
      the vector. Low levels of P antigen expression could also be detected in two
      primary cell types, human umbilical vein endothelial cells (HUVEC) and normal
      human lung fibroblasts (NHLF). In addition, vector binding occurred in both cell
      types and was inhibited by globoside, indicating the involvement of P antigen in
      virus binding to these cells. These primary cells could be efficiently transduced
      with the recombinant vector. These data suggest that (i) P antigen is expressed
      on a variety of cell types and is involved in binding of parvovirus B19 to human
      cells, (ii) the level of P antigen expression does not correlate with the
      efficiency of viral binding, (iii) P antigen is necessary but not sufficient for
      parvovirus B19 entry into cells, and (iv) parvovirus B19 vectors can be used to
      transduce HUVEC and NHLF. These studies further suggest the existence of a
      putative cellular coreceptor for efficient entry of parvovirus B19 into human
      cells.

PMID- 11287562
TI  - Sequences in the cytoplasmic tail of the gibbon ape leukemia virus envelope
      protein that prevent its incorporation into lentivirus vectors.
AB  - Pseudotyping retrovirus and lentivirus vectors with different viral fusion
      proteins is a useful strategy to alter the host range of the vectors. Although
      lentivirus vectors are efficiently pseudotyped by Env proteins from several
      different subtypes of murine leukemia virus (MuLV), the related protein from
      gibbon ape leukemia virus (GaLV) does not form functional pseudotypes. We have
      determined that this arises because of an inability of GaLV Env to be
      incorporated into lentivirus vector particles. By exploiting the homology between
      the GaLV and MuLV Env proteins, we have mapped the determinants of
      incompatibility in the GaLV Env. Three modifications that allowed GaLV Env to
      pseudotype human immunodeficiency virus type 1 particles were identified: removal
      of the R peptide (C-terminal half of the cytoplasmic domain), replacement of the
      whole cytoplasmic tail with the corresponding MuLV region, and mutation of two
      residues upstream of the R peptide cleavage site. In addition, we have previously
      proposed that removal of the R peptide from MuLV Env proteins enhances their
      fusogenicity by transmitting a conformational change to the ectodomain of the
      protein (Y. Zhao et al., J. Virol. 72:5392-5398, 1998). Our analysis of chimeric
      MuLV/GaLV Env proteins provides further evidence in support of this model and
      suggests that proper Env function involves both interactions within the
      cytoplasmic tail and more long-range interactions between the cytoplasmic tail,
      the membrane-spanning region, and the ectodomain of the protein.

PMID- 11287561
TI  - Herpes simplex virus type 1 entry is inhibited by the cobalt chelate complex CTC
      96.
AB  - The CTC series of cobalt chelates display in vitro and in vivo activity against
      herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). The experiments described
      here identify the stage in the virus life cycle where CTC-96 acts and demonstrate
      that the drug inhibits infection of susceptible cells. CTC-96 at 50 microg/ml has
      no effect on adsorption of virions to Vero cell monolayers. Penetration assays
      reveal that CTC-96 inhibits entry of the virus independent of gC and cellular
      entry receptors. This observation was supported by the failure to detect the
      accumulation of virus-specified proteins and alpha mRNA transcripts when CTC-96
      is present at the onset of infection. Moreover, virion-associated alphaTIF does
      not accumulate in the nucleus of cells infected in the presence of CTC-96. CTC-96
      targets the initial fusion event between the virus and the cell and also inhibits
      cell-to-cell spread and syncytium formation. Furthermore, CTC-96 inhibits plaque
      formation by varicella-zoster virus and vesicular stomatitis virus as efficiently
      as by HSV-1. Collectively, these experiments suggest that CTC-96 is a broad
      spectrum inhibitor of infection by enveloped viruses and that it inhibits HSV-1
      infection at the point of membrane fusion independent of the type of virus and
      cellular receptors present.

PMID- 11287563
TI  - The E8 domain confers a novel long-distance transcriptional repression activity
      on the E8E2C protein of high-risk human papillomavirus type 31.
AB  - Infections with high-risk human papillomaviruses (HPVs) are the major risk factor
      for the development of anogenital cancers. Viral E2 proteins are involved in
      viral DNA replication and regulation of transcription. Repression of the viral
      P97 promoter by E2 proteins has been implicated in the modulation of the
      immortalization capacity and DNA replication properties of high-risk HPVs.
      Analysis of the cis and trans requirements for repression of the HPV type 31
      (HPV31) P97 promoter, however, revealed striking differences between the full
      length E2 and the E8E2C fusion protein which were due to conserved residues W6
      and K7 of the E8 domain. In contrast to E2, E8E2C completely inhibited the P97
      promoter from a single promoter-distal E2 binding site. This novel long-distance
      repression activity of the E8 domain also enabled E8E2C to inhibit the HPV6a P2
      promoter and minimal-promoter constructs containing E2 binding sites. Thus, E8E2C
      may represent the master repressor of viral gene expression during a high-risk
      HPV infection, and changes in the activity of E8E2C might contribute to the
      progression of high-risk HPV-induced lesions.

PMID- 11287564
TI  - Human papillomavirus type 6b virus-like particles are able to activate the Ras
      MAP kinase pathway and induce cell proliferation.
AB  - The initial step in viral infection is the attachment of the virus to the host
      cell via an interaction with its receptor. We have previously shown that a
      receptor for human papillomavirus is the alpha6 integrin. The alpha6 integrin is
      involved in the attachment of epithelial cells with the basement membrane, but
      recent evidence suggests that ligation of many integrins results in intracellular
      signaling events that influence cell proliferation. Here we present evidence that
      exposure of A431 human epithelial cells to human papillomavirus type 6b L1 virus
      like particles (VLPs) results in a dose-dependent increase in cell proliferation,
      as measured by bromodeoxyuridine incorporation. This proliferation is lost if
      VLPs are first denatured or incubated with a monoclonal antibody against L1
      protein. The MEK1 inhibitor PB98059 inhibits the VLP-mediated increase in cell
      proliferation, suggesting involvement of the Ras-MAP kinase pathway. Indeed, VLP
      binding results in rapid phosphorylation of the beta4 integrin upon tyrosine
      residues and subsequent recruitment of the adapter protein Shc to beta4. Within
      30 min, the activation of Ras, Raf, and Erk2 was observed. Finally, the
      upregulation of c-myc mRNA was observed at 60 min. These data indicate that human
      papillomavirus type 6b is able to signal cells via the Ras-MAP kinase pathway to
      induce cell proliferation. We hypothesize that such a mechanism would allow
      papillomaviruses to infect hosts more successfully by increasing the potential
      pool of cells they are able to infect via the initiation of proliferation in
      resting keratinocyte stem and suprabasal cells.

PMID- 11287565
TI  - Role of the cytoplasmic domain of the beta-subunit of integrin alpha(v)beta6 in
      infection by foot-and-mouth disease virus.
AB  - Field isolates of foot-and-mouth disease virus (FMDV) are believed to use RGD
      dependent integrins as cellular receptors in vivo. Using SW480 cell
      transfectants, we have recently established that one such integrin,
      alpha(v)beta6, functions as a receptor for FMDV. This integrin was shown to
      function as a receptor for virus attachment. However, it was not known if the
      alpha(v)beta6 receptor itself participated in the events that follow virus
      binding to the host cell. In the present study, we investigated the effects of
      various deletion mutations in the beta6 cytoplasmic domain on infection. Our
      results show that although loss of the beta6 cytoplasmic domain has little effect
      on virus binding, this domain is essential for infection, indicating a critical
      role in postattachment events. The importance of endosomal acidification in
      alpha(v)beta6-mediated infection was confirmed by experiments showing that
      infection could be blocked by concanamycin A, a specific inhibitor of the
      vacuolar ATPase.

PMID- 11287566
TI  - Vaccine-elicited V3 loop-specific antibodies in rhesus monkeys and control of a
      simian-human immunodeficiency virus expressing a primary patient human
      immunodeficiency virus type 1 isolate envelope.
AB  - Vaccine-elicited antibodies specific for the third hypervariable domain of the
      surface gp120 of human immunodeficiency virus type 1 (HIV-1) (V3 loop) were
      assessed for their contribution to protection against infection in the simian
      human immunodeficiency virus (SHIV)/rhesus monkey model. Peptide vaccine-elicited
      anti-V3 loop antibody responses were examined for their ability to contain
      replication of SHIV-89.6, a nonpathogenic SHIV expressing a primary patient
      isolate HIV-1 envelope, as well as SHIV-89.6P, a pathogenic variant of that
      virus. Low-titer neutralizing antibodies to SHIV-89.6 that provided partial
      protection against viremia following SHIV-89.6 infection were generated. A
      similarly low-titer neutralizing antibody response to SHIV-89.6P that did not
      contain viremia after infection with SHIV-89.6P was generated, but a trend toward
      protection against CD4+ T-lymphocyte loss was seen in these infected monkeys.
      These observations suggest that the V3 loop on some primary patient HIV-1
      isolates may be a partially effective target for neutralizing antibodies induced
      by peptide immunogens.

PMID- 11287567
TI  - Genetic targeting of an adenovirus vector via replacement of the fiber protein
      with the phage T4 fibritin.
AB  - The utility of adenovirus (Ad) vectors for gene therapy is restricted by their
      inability to selectively transduce disease-affected tissues. This limitation may
      be overcome by the derivation of vectors capable of interacting with receptors
      specifically expressed in the target tissue. Previous attempts to alter Ad
      tropism by genetic modification of the Ad fiber have had limited success due to
      structural conflicts between the fiber and the targeting ligand. Here we present
      a strategy to derive an Ad vector with enhanced targeting potential by a radical
      replacement of the fiber protein in the Ad capsid with a chimeric molecule
      containing a heterologous trimerization motif and a receptor-binding ligand. Our
      approach, which capitalized upon the overall structural similarity between the
      human Ad type 5 (Ad5) fiber and bacteriophage T4 fibritin proteins, has resulted
      in the generation of a genetically modified Ad5 incorporating chimeric fiber
      fibritin proteins targeted to artificial receptor molecules. Gene transfer
      studies employing this novel viral vector have demonstrated its capacity to
      efficiently deliver a transgene payload to the target cells in a receptor
      specific manner.

PMID- 11287568
TI  - Polyadenylation in rice tungro bacilliform virus: cis-acting signals and
      regulation.
AB  - The polyadenylation signal of rice tungro bacilliform virus (RTBV) was
      characterized by mutational and deletion analysis. The cis-acting signals
      required to direct polyadenylation conformed to what is known for plant poly(A)
      signals in general and were very similar to those of the related cauliflower
      mosaic virus. Processing was directed by a canonical AAUAAA poly(A) signal, an
      upstream UG-rich region considerably enhanced processing efficiency, and
      sequences downstream of the cleavage site were not required. When present at the
      end of a transcription unit, the cis-acting signals for 3'-end processing were
      highly efficient in both monocot (rice) and dicot (Nicotiana plumbaginifolia)
      protoplasts. In a promoter-proximal position, as in the viral genome, the signal
      was also efficiently processed in rice protoplasts, giving rise to an abundant
      "short-stop" (SS-) RNA. The proportion of SS-RNA was considerably lower in N.
      plumbaginifolia protoplasts. In infected plants, SS-RNA was hardly detectable,
      suggesting either that SS-RNA is unstable in infected plants or that read-through
      of the promoter-proximal poly(A) site is very efficient. SS-RNA is readily
      detectable in transgenic rice plants (A. Kloti, C. Henrich, S. Bieri, X. He, G.
      Chen, P. K. Burkhardt, J. Wunn, P. Lucca, T. Hohn, I. Potrylus, and J. Futterer,
      1999. Plant Mol. Biol. 40:249-266), thus the absence of SS-RNA in infected plants
      can be attributed to poly(A) site bypass in the viral context to ensure
      production of the full-length pregenomic viral RNA. RTBV poly(A) site suppression
      thus depends both on context and the expression system; our results suggest that
      the circular viral minichromosome directs assembly of a transcription-processing
      complex with specific properties to effect read-through of the promoter-proximal
      poly(A) signal.

PMID- 11287569
TI  - Identification and antigenicity of broadly cross-reactive and conserved human
      immunodeficiency virus type 1-derived helper T-lymphocyte epitopes.
AB  - Human immunodeficiency virus (HIV)-specific helper T lymphocytes (HTL) play a key
      role in the immune control of HIV type 1 (HIV-1) infection, and as such are an
      important target of potential HIV-1 vaccines. In order to identify HTL epitopes
      in HIV-1 that might serve as vaccine targets, conserved HIV-1-derived peptides
      bearing an HLA-DR binding supermotif were tested for binding to a panel of the
      most representative HLA-DR molecules. Eleven highly cross-reactive binding
      peptides were identified: three in Gag and eight in Pol. Lymphoproliferative
      responses to this panel of peptides, as well as to the HIV-1 p24 and p66
      proteins, were evaluated with a cohort of 31 HIV-1-infected patients. All 11
      peptides were recognized by peripheral blood mononuclear cells from multiple HIV
      infected donors. Many of the responsive HIV-infected subjects showed recognition
      of multiple peptides, indicating that HIV-1-specific T-helper responses may be
      broadly directed in certain individuals. A strong association existed between
      recognition of the parental recombinant HIV-1 protein and the corresponding HTL
      peptides, suggesting that these peptides represent epitopes that are processed
      and presented during the course of HIV-1 infection. Lastly, responses to the
      supermotif peptides were mediated by CD4(+) T cells and were restricted by major
      histocompatibility complex class II molecules. The epitopes described herein are
      potentially important components of HIV-1 therapeutic and prophylactic vaccines.

PMID- 11287571
TI  - Acutely transforming avian leukosis virus subgroup J strain 966: defective genome
      encodes a 72-kilodalton Gag-Myc fusion protein.
AB  - Avian leukosis virus subgroup J (ALV-J), the most recent member of the avian
      retroviruses, is predominantly associated with myeloid leukosis in meat-type
      chickens. We have previously demonstrated that the acutely transforming virus
      strain 966, isolated from an ALV-J-induced tumor, transformed peripheral blood
      monocyte and bone marrow cells in vitro and induced rapid-onset tumors,
      suggesting transduction of oncogenes (L. N. Payne, A. M. Gillespie, and K. Howes,
      Avian Dis. 37:438-450, 1993). In order to understand the molecular basis for the
      rapid transformation and tumor induction, we have determined the complete genomic
      structure of the provirus of the 966 strain. The sequence of the 966 provirus
      clone revealed that its genome is closely related to that of HPRS-103 but is
      defective, with the entire pol and parts of the gag and env genes replaced by a
      1,491-bp sequence representing exons 2 and 3 of the c-myc gene. LSTC-IAH30, a
      stable cell line derived from turkey monocyte cultures transformed by the 966
      strain of ALV-J, expressed a 72-kDa Gag-Myc fusion protein. The identification of
      the myc gene in 966 virus as well as in several other ALV-J-induced tumors
      suggested that the induction of myeloid tumors by this new subgroup of ALV occurs
      through mechanisms involving the activation of the c-myc oncogene.

PMID- 11287570
TI  - Envelope glycoprotein determinants of neutralization resistance in a simian-human
      immunodeficiency virus (SHIV-HXBc2P 3.2) derived by passage in monkeys.
AB  - The simian-human immunodeficiency virus SHIV-HXBc2 contains the envelope
      glycoproteins of a laboratory-adapted, neutralization-sensitive human
      immunodeficiency virus type 1 variant, HXBc2. Serial in vivo passage of the
      nonpathogenic SHIV-HXBc2 generated SHIV KU-1, which causes rapid CD4(+) T-cell
      depletion and an AIDS-like illness in monkeys. A molecularly cloned pathogenic
      SHIV, SHIV-HXBc2P 3.2, was derived from the SHIV KU-1 isolate and differs from
      the parental SHIV-HXBc2 by only 12 envelope glycoprotein amino acid residues.
      Relative to SHIV-HXBc2, SHIV-HXBc2P 3.2 was resistant to neutralization by all of
      the antibodies tested with the exception of the 2G12 antibody. The sequence
      changes responsible for neutralization resistance were located in variable
      regions of the gp120 exterior envelope glycoprotein and in the gp41 transmembrane
      envelope glycoprotein. The 2G12 antibody, which neutralized SHIV-HXBc2 and SHIV
      HXBc2P 3.2 equally, bound the HXBc2 and HXBc2P 3.2 envelope glycoproteins on the
      cell surface comparably. The ability of the other tested antibodies to achieve
      saturation was less for the HXBc2P 3.2 envelope glycoproteins than for the HXBc2
      envelope glycoproteins, even though the affinity of the antibodies for the two
      envelope glycoproteins was similar. Thus, a highly neutralization-sensitive SHIV,
      by modifying both gp120 and gp41 glycoproteins, apparently achieves a
      neutralization-resistant state by decreasing the saturability of its envelope
      glycoproteins by antibodies.

PMID- 11287572
TI  - Efficient translation initiation is required for replication of bovine viral
      diarrhea virus subgenomic replicons.
AB  - An internal ribosome entry site (IRES) mediates translation initiation of bovine
      viral diarrhea virus (BVDV) RNA. Studies have suggested that a portion of the
      N(pro) open reading frame (ORF) is required, although its exact function has not
      been defined. Here we show that a subgenomic (sg) BVDV RNA in which the NS3 ORF
      is preceded only by the 5' nontranslated region did not replicate to detectable
      levels following transfection. However, RNA synthesis and cytopathic effects were
      observed following serial passage in the presence of a noncytopathic helper
      virus. Five sg clones derived from the passaged virus contained an identical,
      silent substitution near the beginning of the NS3 coding sequence (G400U), as
      well as additional mutations. Four of the reconstructed mutant RNAs replicated in
      transfected cells, and in vitro translation showed increased levels of NS3 for
      the mutant RNAs compared to that of wild-type (wt) MetNS3. To more precisely
      dissect the role of these mutations, we constructed two sg derivatives: ad3.10,
      which contains only the G400U mutation, and ad3.7, with silent substitutions
      designed to minimize RNA secondary structure downstream of the initiator AUG.
      Both RNAs replicated and were translated in vitro to similar levels. Moreover,
      ad3.7 and ad3.10, but not wt MetNS3, formed toeprints downstream of the initiator
      AUG codon in an assay for detecting the binding of 40S ribosomal subunits and 43S
      ribosomal complexes to the IRES. These results suggest that a lack of stable RNA
      secondary structure(s), rather than a specific RNA sequence, immediately
      downstream of the initiator AUG is important for optimal translation initiation
      of pestivirus RNAs.

PMID- 11287573
TI  - Jaagsiekte sheep retrovirus proviral clone JSRV(JS7), derived from the JS7 lung
      tumor cell line, induces ovine pulmonary carcinoma and is integrated into the
      surfactant protein A gene.
AB  - Ovine pulmonary carcinoma (OPC) is a contagious neoplasm of alveolar epithelial
      type II (ATII) or Clara cells caused by a type D/B chimeric retrovirus,
      jaagsiekte sheep retrovirus (JSRV). Here we report the isolation, sequencing,
      pathogenicity, and integration site of a JSRV provirus isolated from a sheep lung
      tumor cell line (JS7). The sequence of the virus was 93 to 99% identical to other
      JSRV isolates and contained all of the expected open reading frames. To produce
      virions and test its infectivity, the JS7 provirus (JSRV(JS7)) was cloned into a
      plasmid containing a cytomegalovirus promoter and transfected into 293T cells.
      After intratracheal inoculation with virions from concentrated supernatant fluid,
      JSRV-associated OPC lesions were found in one of four lambs, confirming that
      JSRV(JS7) is pathogenic. In JS7-cell DNA, the viral genome was inserted in the
      protein-coding region for the surfactant protein A (SP-A) gene, which is highly
      expressed in ATII cells, in an orientation opposite to the direction of
      transcription of the SP-A gene. No significant transcription was detected from
      either the viral or the SP-A gene promoter in the JS7 cell line at passage level
      170. The oncogenic significance of the JSRV proviral insertion involving the SP-A
      locus in the JS7 tumor cell line is unknown.

PMID- 11287575
TI  - Replacement of the V3 region of gp120 with SDF-1 preserves the infectivity of T
      cell line-tropic human immunodeficiency virus type 1.
AB  - Interaction between the human immunodeficiency virus type 1 (HIV-1) envelope and
      the relevant chemokine receptors is crucial for subsequent membrane fusion and
      viral entry. Although the V3 region of gp120 is known to determine the cell
      tropism as well as the coreceptor usage, the significance of the binding of the
      V3 region to the chemokine receptor has not been fully understood. To address
      this issue, we adopted the pseudotyped virus infection assay in which the V3
      region of the T-cell line-tropic (T-tropic) NL4-3 envelope was replaced with a
      portion of stromal cell-derived factor 1 (SDF-1), the ligand of CXCR4. The V3
      region of the NL4-3 envelope expression vector was replaced with three different
      stretches of SDF-1 cDNA. Expression of each chimeric envelope protein was
      confirmed by immunoprecipitation and Western blotting. Luciferase reporter
      viruses were prepared by cotransfection of the pNL4-3.Luc.E(-)R(-) vector and
      each chimeric envelope expression vector, and the infection assay was then
      carried out. We showed that pseudotyped viruses with one of the chimeric
      envelopes, NL4-3/SDF1-51, could infect U87.CD4.CXCR4 but not U87.CD4 or U87.CXCR4
      cells and that this infection was inhibited by the ligand of CXCR4, SDF-1beta, by
      anti-human SDF-1 antibody, or by an anti-CD4 antibody, Leu3a, in a dose-dependent
      manner. Furthermore, chimeric NL4-3/SDF1-51 gp120 significantly inhibited binding
      of labeled SDF-1 to CXCR4. It was suggested that replacement of the V3 region of
      the NL4-3 envelope with SDF-1 preserved the CD4-dependent infectivity of T-tropic
      HIV-1. These results indicate that binding between the V3 region and the relevant
      coreceptor is important for viral entry, whether its amino acid sequence is
      indigenous to the virus or not.

PMID- 11287574
TI  - Hepatitis B virus HBx protein activation of cyclin A-cyclin-dependent kinase 2
      complexes and G1 transit via a Src kinase pathway.
AB  - Numerous studies have demonstrated that the hepatitis B virus HBx protein
      stimulates signal transduction pathways and may bind to certain transcription
      factors, particularly the cyclic AMP response element binding protein, CREB. HBx
      has also been shown to promote early cell cycle progression, possibly by
      functionally replacing the TATA-binding protein-associated factor 250
      (TAF(II)250), a transcriptional coactivator, and/or by stimulating cytoplasmic
      signal transduction pathways. To understand the basis for early cell cycle
      progression mediated by HBx, we characterized the molecular mechanism by which
      HBx promotes deregulation of the G0 and G1 cell cycle checkpoints in growth
      arrested cells. We demonstrate that TAF(II)250 is absolutely required for HBx
      activation of the cyclin A promoter and for promotion of early cell cycle transit
      from G0 through G1. Thus, HBx does not functionally replace TAF(II)250 for
      transcriptional activity or for cell cycle progression, in contrast to a previous
      report. Instead, HBx is shown to activate the cyclin A promoter, induce cyclin A
      cyclin-dependent kinase 2 complexes, and promote cycling of growth-arrested cells
      into G1 through a pathway involving activation of Src tyrosine kinases. HBx
      stimulation of Src kinases and cyclin gene expression was found to force growth
      arrested cells to transit through G1 but to stall at the junction with S phase,
      which may be important for viral replication.

PMID- 11287576
TI  - Mutational evidence for an internal fusion peptide in flavivirus envelope protein
      E.
AB  - The envelope protein E of the flavivirus tick-borne encephalitis (TBE) virus
      promotes cell entry by inducing fusion of the viral membrane with an
      intracellular membrane after uptake by endocytosis. This protein differs from
      other well-studied viral and cellular fusion proteins because of its distinct
      molecular architecture and apparent lack of involvement of coiled coils in the
      low-pH-induced structural transitions that lead to fusion. A highly conserved
      loop (the cd loop), which resides at the distal tip of each subunit and is mostly
      buried in the subunit interface of the native E homodimer at neutral pH, has been
      hypothesized to function as an internal fusion peptide at low pH, but this has
      not yet been shown experimentally. It was predicted by examination of the X-ray
      crystal structure of the TBE virus E protein (F. A. Rey et al., Nature 375:291
      298, 1995) that mutations at a specific residue within this loop (Leu 107) would
      not cause the native structure to be disrupted. We therefore introduced amino
      acid substitutions at this position and, using recombinant subviral particles,
      investigated the effects of these changes on fusion and related properties.
      Replacement of Leu with hydrophilic amino acids strongly impaired (Thr) or
      abolished (Asp) fusion activity, whereas a Phe mutant still retained a
      significant degree of fusion activity. Liposome coflotation experiments showed
      that the fusion-negative Asp mutant did not form a stable interaction with
      membranes at low pH, although it was still capable of undergoing the structural
      rearrangements required for fusion. These data support the hypothesis that the cd
      loop may be directly involved in interactions with target membranes during
      fusion.

PMID- 11287577
TI  - Muscle-specific overexpression of the adenovirus primary receptor CAR overcomes
      low efficiency of gene transfer to mature skeletal muscle.
AB  - Significant levels of adenovirus (Ad)-mediated gene transfer occur only in
      immature muscle or in regenerating muscle, indicating that a developmentally
      regulated event plays a major role in limiting transgene expression in mature
      skeletal muscle. We have previously shown that in developing mouse muscle,
      expression of the primary Ad receptor CAR is severely downregulated during muscle
      maturation. To evaluate how global expression of CAR throughout muscle affects Ad
      vector (AdV)-mediated gene transfer into mature skeletal muscle, we produced
      transgenic mice that express the CAR cDNA under the control of the muscle
      specific creatine kinase promoter. Five-month-old transgenic mice were compared
      to their nontransgenic littermates for their susceptibility to AdV transduction.
      In CAR transgenics that had been injected in the tibialis anterior muscle with
      AdVCMVlacZ, increased gene transfer was demonstrated by the increase in the
      number of transduced muscle fibers (433 +/- 121 in transgenic mice versus 8 +/- 4
      in nontransgenic littermates) as well as the 25-fold increase in overall beta
      galactosidase activity. Even when the reporter gene was driven by a more
      efficient promoter (the cytomegalovirus enhancer-chicken beta-actin gene
      promoter), differential transducibility was still evident (893 +/- 149 versus 153
      +/- 30 fibers; P < 0.001). Furthermore, a fivefold decrease in the titer of
      injected AdV still resulted in significant transduction of muscle (253 +/- 130
      versus 14 +/- 4 fibers). The dramatic enhancement in AdV-mediated gene transfer
      to mature skeletal muscle that is observed in the CAR transgenics indicates that
      prior modulation of the level of CAR expression can overcome the poor AdV
      transducibility of mature skeletal muscle and significant transduction can be
      obtained at low titers of AdV.

PMID- 11287578
TI  - Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive
      genes and upregulate proliferation-associated and NF-kappaB-responsive genes in
      cervical keratinocytes.
AB  - Infection with high-risk human papillomaviruses (HPV) is a major risk factor for
      development of cervical cancer. Expression of the HPV E6 and E7 oncoproteins
      increases in differentiating keratinocytes, resulting in inactivation of the p53
      and retinoblastoma proteins, two important transcriptional regulators. We used
      cDNA microarrays to examine global alterations in gene expression in
      differentiating cervical keratinocytes after infection with retroviruses encoding
      HPV type 16 (HPV-16) E6 and E7. Expression of 80 cellular genes (approximately 4%
      of the genes on the array) was altered reproducibly by E6 and/or E7. Cluster
      analysis classified these genes into three functional groups: (i) interferon
      (IFN)-responsive genes, (ii) genes stimulated by NF-kappaB, and (iii) genes
      regulated in cell cycle progression and DNA synthesis. HPV-16 E6 or a dominant
      negative p53 protein downregulated multiple IFN-responsive genes. E6 decreased
      expression of IFN-alpha and -beta, downregulated nuclear STAT-1 protein, and
      decreased binding of STAT-1 to the IFN-stimulated response element. E7 alone was
      less effective; however, coexpression of E6 and E7 downregulated IFN-responsive
      genes more efficiently than E6. The HPV-16 E6 protein also stimulated expression
      of multiple genes known to be inducible by NF-kappaB and AP-1. E6 enhanced
      expression of functional components of the NF-kappaB signal pathway, including
      p50, NIK, and TRAF-interacting protein, and increased binding to NF-kappaB and AP
      1 DNA consensus binding sites. Secretion of interleukin-8, RANTES, macrophage
      inflammatory protein 1alpha, and 10-kappaDa IFN-gamma-inducible protein were
      increased in differentiating keratinocytes by E6. Thus, high-level expression of
      the HPV-16 E6 protein in differentiating keratinocytes directly alters expression
      of genes that influence host resistance to infection and immune function.

PMID- 11287579
TI  - Analyses of single-amino-acid substitution mutants of adenovirus type 5 E1B-55K
      protein.
AB  - The E1B-55K protein plays an important role during human adenovirus type 5
      productive infection. In the early phase of the viral infection, E1B-55K binds to
      and inactivates the tumor suppressor protein p53, allowing efficient replication
      of the virus. During the late phase of infection, E1B-55K is required for
      efficient nucleocytoplasmic transport and translation of late viral mRNAs, as
      well as for host cell shutoff. In an effort to separate the p53 binding and
      inactivation function and the late functions of the E1B-55K protein, we have
      generated 26 single-amino-acid mutations in the E1B-55K protein. These mutants
      were characterized for their ability to modulate the p53 level, interact with the
      E4orf6 protein, mediate viral late-gene expression, and support virus replication
      in human cancer cells. Of the 26 mutants, 24 can mediate p53 degradation as
      efficiently as the wild-type protein. Two mutants, R240A (ONYX-051) and H260A
      (ONYX-053), failed to degrade p53 in the infected cells. In vitro binding assays
      indicated that R240A and H260A bound p53 poorly compared to the wild-type
      protein. When interaction with another viral protein, E4orf6, was examined, H260A
      significantly lost its ability to bind E4orf6, while R240A was fully functional
      in this interaction. Another mutant, T255A, lost the ability to bind E4orf6, but
      unexpectedly, viral late-gene expression was not affected. This raised the
      possibility that the interaction between E1B-55K and E4orf6 was not required for
      efficient viral mRNA transport. Both R240A and H260A have retained, at least
      partially, the late functions of wild-type E1B-55K, as determined by the
      expression of viral late proteins, host cell shutoff, and lack of a cold
      sensitive phenotype. Virus expressing R240A (ONYX-051) replicated very
      efficiently in human cancer cells, while virus expressing H260A (ONYX-053) was
      attenuated compared to wild-type virus dl309 but was more active than ONYX-015.
      The ability to separate the p53-inactivation activity and the late functions of
      E1B-55K raises the possibility of generating adenovirus variants that retain the
      tumor selectivity of ONYX-015 but can replicate more efficiently than ONYX-015 in
      a broad spectrum of cell types.

PMID- 11287581
TI  - Global impact of influenza virus on cellular pathways is mediated by both
      replication-dependent and -independent events.
AB  - Influenza virus, the causative agent of the common flu, is a worldwide health
      problem with significant economic consequences. Studies of influenza virus
      biology have revealed elaborate mechanisms by which the virus interacts with its
      host cell as it inhibits the synthesis of cellular proteins, evades the innate
      antiviral response, and facilitates production of viral RNAs and proteins. With
      the advent of DNA array technology it is now possible to obtain a large-scale
      view of how viruses alter the environment within the host cell. In this study,
      the cellular response to influenza virus infection was examined by monitoring the
      steady-state mRNA levels for over 4,600 cellular genes. Infections with active
      and inactivated influenza viruses identified changes in cellular gene expression
      that were dependent on or independent of viral replication, respectively. Viral
      replication resulted in the downregulation of many cellular mRNAs, and the effect
      was enhanced with time postinfection. Interestingly, several genes involved in
      protein synthesis, transcriptional regulation, and cytokine signaling were
      induced by influenza virus replication, suggesting that some may play essential
      or accessory roles in the viral life cycle or the host cell's stress response.
      The gene expression pattern induced by inactivated viruses revealed induction of
      the cellular metallothionein genes that may represent a protective response to
      virus-induced oxidative stress. Genome-scale analyses of virus infections will
      help us to understand the complexities of virus-host interactions and may lead to
      the discovery of novel drug targets or antiviral therapies.

PMID- 11287580
TI  - Regulation of human immunodeficiency virus type 1 infection, beta-chemokine
      production, and CCR5 expression in CD40L-stimulated macrophages: immune control
      of viral entry.
AB  - Mononuclear phagocytes (MP) and T lymphocytes play a pivotal role in the host
      immune response to human immunodeficiency virus type 1 (HIV-1) infection.
      Regulation of such immune responses can be mediated, in part, through the
      interaction of the T-lymphocyte-expressed molecule CD40 ligand (CD40L) with its
      receptor on MP, CD40. Upregulation of CD40L on CD4+ peripheral blood mononuclear
      cells during advanced HIV-1 disease has previously been reported. Based on this
      observation, we studied the influence of CD40L-CD40 interactions on MP effector
      function and viral regulation in vitro. We monitored productive viral infection,
      cytokine and beta-chemokine production, and beta-chemokine receptor expression in
      monocyte-derived macrophages (MDM) after treatment with soluble CD40L. Beginning
      1 day after infection and continuing at 3-day intervals, treatment with CD40L
      inhibited productive HIV-1 infection in MDM in a dose-dependent manner. A
      concomitant and marked upregulation of beta-chemokines (macrophage inhibitory
      proteins 1alpha and 1beta and RANTES [regulated upon activation normal T-cell
      expressed and secreted]) and the proinflammatory cytokine tumor necrosis factor
      alpha (TNF-alpha) was observed in HIV-1-infected and CD40L-treated MDM relative
      to either infected or activated MDM alone. The addition of antibodies to RANTES
      or TNF-alpha led to a partial reversal of the CD40L-mediated inhibition of HIV-1
      infection. Surface expression of CD4 and the beta-chemokine receptor CCR5 was
      reduced on MDM in response to treatment with CD40L. In addition, treatment of
      CCR5- and CD4-transfected 293T cells with secretory products from CD40L
      stimulated MDM prior to infection with a CCR5-tropic HIV-1 reporter virus led to
      inhibition of viral entry. In conclusion, we demonstrate that CD40L-mediated
      inhibition of viral entry coincides with a broad range of MDM immune effector
      responses and the down-modulation of CCR5 and CD4 expression.

PMID- 11287582
TI  - L1 interaction domains of papillomavirus l2 necessary for viral genome
      encapsidation.
AB  - BPHE-1 cells, which harbor 50 to 200 viral episomes, encapsidate viral genome and
      generate infectious bovine papillomavirus type 1 (BPV1) upon coexpression of
      capsid proteins L1 and L2 of BPV1, but not coexpression of BPV1 L1 and human
      papillomavirus type 16 (HPV16) L2. BPV1 L2 bound in vitro via its C-terminal 85
      residues to purified L1 capsomers, but not with intact L1 virus-like particles in
      vitro. However, when the efficiency of BPV1 L1 coimmunoprecipitation with a
      series of BPV1 L2 deletion mutants was examined in vivo, the results suggested
      that residues 129 to 246 and 384 to 460 contain independent L1 interaction
      domains. An L2 mutant lacking the C-terminal L1 interaction domain was impaired
      for encapsidation of the viral genome. Coexpression of BPV1 L1 and a chimeric L2
      protein composed of HPV16 L2 residues 1 to 98 fused to BPV1 L2 residues 99 to 469
      generated infectious virions. However, inefficient encapsidation was seen when L1
      was coexpressed with either BPV1 L2 with residues 91 to 246 deleted or with BPV1
      L2 with residues 1 to 225 replaced with HPV16 L2. Impaired genome encapsidation
      did not correlate closely with impairment of the L2 proteins either to localize
      to promyelocytic leukemia oncogenic domains (PODs) or to induce localization of
      L1 or E2 to PODs. We conclude that the L1-binding domain located near the C
      terminus of L2 may bind L1 prior to completion of capsid assembly, and that both
      L1-binding domains of L2 are required for efficient encapsidation of the viral
      genome.

PMID- 11287583
TI  - Multiple immediate-early gene-deficient herpes simplex virus vectors allowing
      efficient gene delivery to neurons in culture and widespread gene delivery to the
      central nervous system in vivo.
AB  - Herpes simplex virus (HSV) has several potential advantages as a vector for
      delivering genes to the nervous system. The virus naturally infects and remains
      latent in neurons and has evolved the ability of highly efficient retrograde
      transport from the site of infection at the periphery to the site of latency in
      the spinal ganglia. HSV is a large virus, potentially allowing the insertion of
      multiple or very large transgenes. Furthermore, HSV does not integrate into the
      host chromosome, removing any potential for insertional activation or
      inactivation of cellular genes. However, the development of HSV vectors for the
      central nervous system that exploit these properties has been problematical. This
      has mainly been due to either vector toxicity or an inability to maintain
      transgene expression. Here we report the development of highly disabled versions
      of HSV-1 deleted for ICP27, ICP4, and ICP34.5/open reading frame P and with an
      inactivating mutation in VP16. These viruses express only minimal levels of any
      of the immediate-early genes in noncomplementing cells. Transgene expression is
      maintained for extended periods with promoter systems containing elements from
      the HSV latency-associated transcript promoter (J. A. Palmer et al., J. Virol.
      74:5604-5618, 2000). Unlike less-disabled viruses, these vectors allow highly
      effective gene delivery both to neurons in culture and to the central nervous
      system in vivo. Gene delivery in vivo is further enhanced by the retrograde
      transport capabilities of HSV. Here the vector is efficiently transported from
      the site of inoculation to connected sites within the nervous system. This is
      demonstrated by gene delivery to both the striatum and substantia nigra following
      striatal inoculation; to the spinal cord, spinal ganglia, and brainstem following
      injection into the spinal cord; and to retinal ganglion neurons following
      injection into the superior colliculus and thalamus.

PMID- 11287584
TI  - Functional characterization of the N termini of murine leukemia virus envelope
      proteins.
AB  - The function of the N terminus of the murine leukemia virus (MuLV) surface (SU)
      protein was examined. A series of five chimeric envelope proteins (Env) were
      generated in which the N terminus of amphotropic 4070A was replaced by equivalent
      sequences from ecotropic Moloney MuLV (M-MuLV). Viral titers of these chimeras
      indicate that exchange with homologous sequences could be tolerated, up to
      V17eco/T15ampho (crossover III). Constructs encoding the first 28 amino acids
      (aa) of ecotropic M-MuLV resulted in Env expression and binding to the receptor;
      however, the virus titer was reduced 5- to 45-fold, indicating a postbinding
      block. Additional exchange beyond the first 28 aa of ecotropic MuLV Env resulted
      in defective protein expression. These N-terminal chimeras were also introduced
      into the AE4 chimeric Env backbone containing the amphotropic receptor binding
      domain joined at the hinge region to the ecotropic SU C terminus. In this
      backbone, introduction of the first 17 aa of the ecotropic Env protein
      significantly increased the titer compared to that of its parental chimera AE4,
      implying a functional coordination between the N terminus of SU and the C
      terminus of the SU and/or transmembrane proteins. These data functionally dissect
      the N-terminal sequence of the MuLV Env protein and identify differential effects
      on receptor-mediated entry.

PMID- 11287585
TI  - Human foamy virus capsid formation requires an interaction domain in the N
      terminus of Gag.
AB  - Retroviral Gag expression is sufficient for capsid assembly, which occurs through
      interaction between distinct Gag domains. Human foamy virus (HFV) capsids
      assemble within the cytoplasm, although their budding, which mainly occurs in the
      endoplasmic reticulum, requires the presence of homologous Env. Yet little is
      known about the molecular basis of HFV Gag precursor assembly. Using fusions
      between HFV Gag and a nuclear reporter protein, we have identified a strong
      interaction domain in the N terminus of HFV Gag which is predicted to contain a
      conserved coiled-coil motif. Deletion within this region in an HFV provirus
      abolishes viral production through inhibition of capsid assembly.

PMID- 11287586
TI  - Herpes simplex virus IE63 (ICP27) protein interacts with spliceosome-associated
      protein 145 and inhibits splicing prior to the first catalytic step.
AB  - The multifunctional herpes simplex virus type 1 (HSV-1) protein IE63 (ICP27)
      interacts with the essential pre-mRNA splicing factor, spliceosome-associated
      protein 145 (SAP145), and in infected cells IE63 and SAP145 colocalize. This
      interaction was reduced or abrogated completely using extracts from cells
      infected with IE63 viral mutants, with mutations in IE63 KH and Sm homology
      domains, which do not exhibit host shutoff or inhibit splicing. In the presence
      of IE63, splicing in vitro was inhibited prior to the first catalytic step and
      the B/C complex formed during splicing was shifted up in mobility and reduced in
      intensity. With the use of splicing extracts, IE63 and SAP145 both comigrated
      with the B/C complex, suggesting that they interact within this complex to
      inhibit B/C complex formation or conversion. The inhibition of splicing may
      facilitate the export of viral or cellular transcripts, possibly via other
      protein partners of IE63. These data provide important new insights into how IE63
      influences pre-mRNA processing during HSV-1 infection.

PMID- 11287587
TI  - Enhancer and long-term expression functions of herpes simplex virus type 1
      latency-associated promoter are both located in the same region.
AB  - During herpes simplex virus type 1 (HSV-1) latent infection in vivo, the latency
      associated promoter (LAP) is the only promoter to remain highly active long term.
      In a previous attempt to characterize LAP activity in vitro and in a mouse model,
      we showed that a 1.5-kb fragment called the long-term expression element (LTE),
      located immediately downstream from the transcriptional start site of LAP, was
      able to (i) increase gene expression in an orientation-independent manner,
      regardless of the cell type or the promoter used in vitro (enhancer activity) and
      (ii) keep LAP active during latency in vivo (long-term expression activity) (H.
      Berthomme, J. Lokensgard, L. Yang, T. Margolis, and L. T. Feldman, J. Virol.
      74:3613-3622, 2000). To determine if these two functions could be separated
      genetically, we conducted a mutational analysis on the LTE and analyzed the
      effect on the LAP-LTE properties in both transient expression in cell culture and
      mouse dorsal root ganglia lytic and latent infection. In this report, we show
      that the first half of the LTE sequence, corresponding to the region previously
      described as LAP2 or exon1, encodes the enhancer function. This same region is
      also required to keep the LAP active during latency. These results exclude the
      intron region as containing any significant enhancer activity or any ability to
      keep the LAP active during latency. The results also show that these two
      functions have not been separated, leaving open the possibility that there is no
      long-term expression function per se but that the enhancer itself may function to
      keep the LAP active during latency by raising the level of expression to a
      detectable one. Further mutational analysis will be required to determine if
      these two potential functions continue to cosegregate.

PMID- 11287588
TI  - In vivo accumulation of cyclin A and cellular replication factors in autonomous
      parvovirus minute virus of mice-associated replication bodies.
AB  - Autonomous parvovirus minute virus of mice (MVM) DNA replication is strictly
      dependent on cellular factors expressed during the S phase of the cell cycle.
      Here we report that MVM DNA replication proceeds in specific nuclear structures
      termed autonomous parvovirus-associated replication bodies, where components of
      the basic cellular replication machinery accumulate. The presence of DNA
      polymerases alpha and delta in these bodies suggests that MVM utilizes partially
      preformed cellular replication complexes for its replication. The recruitment of
      cyclin A points to a role for this cell cycle factor in MVM DNA replication
      beyond its involvement in activating the conversion of virion single-stranded DNA
      to the duplex replicative form.

PMID- 11287589
TI  - Measles viruses on throat swabs from measles patients use signaling lymphocytic
      activation molecule (CDw150) but not CD46 as a cellular receptor.
AB  - Both CD46 and signaling lymphocytic activation molecule (SLAM) have been shown to
      act as cellular receptors for measles virus (MV). The viruses on throat swabs
      from nine patients with measles in Japan were titrated on Vero cells stably
      expressing human SLAM. Samples from all but two patients produced numerous
      plaques on SLAM-expressing Vero cells, whereas none produced any plaques on Vero
      cells endogenously expressing CD46. The Edmonston strain of MV, which can use
      either CD46 or SLAM as a receptor, produced comparable titers on these two types
      of cells. The results strongly suggest that the viruses in the bodies of measles
      patients use SLAM but probably not CD46 as a cellular receptor.

PMID- 11287590
TI  - The LD78beta isoform of MIP-1alpha is the most potent CC-chemokine in inhibiting
      CCR5-dependent human immunodeficiency virus type 1 replication in human
      macrophages.
AB  - The CC-chemokines RANTES, macrophage inflammatory protein 1alpha (MIP-1alpha),
      and MIP-1beta are natural ligands for the CC-chemokine receptor CCR5. MIP-1alpha,
      also known as LD78alpha, has an isoform, LD78beta, which was identified as the
      product of a nonallelic gene. The two isoforms differ in only 3 amino acids.
      LD78beta was recently reported to be a much more potent CCR5 agonist than
      LD78alpha and RANTES in inducing intracellular Ca2+ signaling and chemotaxis.
      CCR5 is expressed by human monocytes/macrophages (M/M) and represents an
      important coreceptor for macrophage-tropic, CCR5-using (R5) human
      immunodeficiency virus type 1 (HIV-1) strains to infect the cells. We compared
      the antiviral activities of LD78beta and the other CC-chemokines in M/M. LD78beta
      at 100 ng/ml almost completely blocked HIV-1 replication, while at the same
      concentration LD78alpha had only weak antiviral activity. Moreover, when HIV-1
      infection in M/M was monitored by a flow cytometric analysis using p24 antigen
      intracellular staining, LD78beta proved to be the most antivirally active of the
      chemokines. RANTES, once described as the most potent chemokine in inhibiting R5
      HIV-1 infection, was found to be considerably less active than LD78beta. LD78beta
      strongly downregulated CCR5 expression in M/M, thereby explaining its potent
      antiviral activity.

PMID- 11287591
TI  - PR domain of rous sarcoma virus Gag causes an assembly/budding defect in insect
      cells.
AB  - While baculovirus expression of Gag proteins from numerous retroviruses has led
      reliably to production of virus-like particles (VLPs), we observed that
      expression of Rous sarcoma virus Gag failed to produce VLPs. Transmission and
      scanning electron microscopy analysis revealed that the Gag protein reached the
      plasma membrane but was unable to correctly form particles. Addition of a
      myristylation signal had no effect on the budding defect, but deletion of the PR
      domain of Gag restored normal budding. The resulting VLPs were morphologically
      distinct from human immunodeficiency virus type 1 VLPs expressed in parallel.

PMID- 11287592
TI  - Restoration of anti-human immunodeficiency virus type 1 (HIV-1) responses in CD8+
      T cells from late-stage patients on prolonged antiretroviral therapy by
      stimulation in vitro with HIV-1 protein-loaded dendritic cells.
AB  - We demonstrate that dendritic cells loaded in vitro with human immunodeficiency
      virus type 1 (HIV-1) protein-liposome complexes activate HLA class I-restricted
      anti-HIV-1 cytotoxic T-lymphocyte and gamma interferon (IFN-gamma) responses in
      autologous CD8+ T cells from late-stage HIV-1-infected patients on prolonged
      combination drug therapy. Interleukin-12 enhanced this effect through an
      interleukin-2- and IFN-gamma-mediated pathway. This suggests that dendritic cells
      from HIV-1-infected persons can be engineered to evoke stronger anti-HIV-1 CD8+ T
      cell reactivity as a strategy to augment antiretroviral therapy.

PMID- 11287593
TI  - Human T-cell leukemia virus type 1 (HTLV-1) infection of mice: proliferation of
      cell clones with integrated HTLV-1 provirus in lymphoid organs.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is suggested to cause adult T-cell
      leukemia after 40 to 50 years of latency in a small percentage of carriers.
      However, little is known about the pathophysiology of the latent period and the
      reservoir organs where polyclonal proliferation of cells harboring integrated
      provirus occurs. The availability of animal models would be useful to analyze the
      latent period of HTLV-1 infection. At 18 months after HTLV-1 infection of C3H/HeJ
      mice inoculated with the MT-2 cell line, which is an HTLV-1-producing human T
      cell line, HTLV-1 provirus was detected in spleen DNA from eight of nine mice. No
      more than around 100 proviruses were found per 10(5) spleen cells. Cellular
      sequences flanking the 3' long terminal repeat (LTR) and the clonalities of the
      cells which harbor integrated HTLV-1 provirus were analyzed by linker-mediated
      PCR. The results showed that the flanking sequences are of mouse genome origin
      and that polyclonal proliferation of the spleen cells harboring integrated HTLV-1
      provirus had occurred in three mice. A sequence flanking the 5' LTR was isolated
      from one of the mice and revealed the presence of a 6-nucleotide duplication of
      cellular sequences, consistent with typical retroviral integration. Moreover, PCR
      was performed on DNA from infected tissues, with LTR primers and primers derived
      from seven novel flanking sequences of the three mice. Data revealed that the
      expected PCR products were found from lymphatic tissues of the same mouse,
      suggesting that the lymphatic tissues were the reservoir organs for the infected
      and proliferating cell clones. The mouse model described here should be useful
      for analysis of the carrier state of HTLV-1 infection in humans.

PMID- 11287594
TI  - AIDS vaccination studies using an ex vivo feline immunodeficiency virus model:
      reevaluation of neutralizing antibody levels elicited by a protective and a
      nonprotective vaccine after removal of antisubstrate cell antibodies.
AB  - In the feline immunodeficiency virus system, immunization with a fixed-infected
      cell vaccine conferred protection against virulent homologous challenge but the
      immune effectors involved remained elusive. In particular, few or no neutralizing
      antibodies were detected in sera from vaccinated cats. Here we show that, when
      preadsorbed with selected feline cells, the same sera revealed clearly evident
      virus-neutralizing activity. Because high titers of neutralizing antibody in cell
      adsorbed sera from 23 cats immunized with fixed-infected-cell or whole
      inactivated-virus vaccines correlated with protection, it is likely that they
      were more important for protection than formerly realized. In vitro, the fixed
      cell vaccine efficiently removed neutralizing antibody from immune sera while the
      whole-inactivated-virus vaccine was much less effective.

PMID- 11287596
TI  - Virus-specific and bystander CD8+ T-cell proliferation in the acute and
      persistent phases of a gammaherpesvirus infection.
AB  - The cycling characteristics of CD8+ T cells specific for two lytic-phase epitopes
      of murine gammaherpesvirus 68 (gammaHV68) have been analyzed for mice with high
      or low levels of virus persistence. The extent of cell division is generally
      reflective of the antigen load and suggests that gammaHV68 may be regularly
      reactivating from latency for some months after the resolution of the acute phase
      of the infectious process. Although gammaHV68 infection is also associated with
      massive proliferation of lymphocytes that are not obviously specific for the
      virus, the level of "bystander-induced" cycling in a population of influenza
      virus-specific CD8+ T cells was generally fourfold lower than the extent of cell
      division seen for the antigen-driven, gammaHV68-specific response. The overall
      conclusion is that turnover rates substantially in excess of 5 to 10% over 6 days
      for CD8+ "memory" T-cell populations are likely to be reflective of continued
      antigenic exposure.

PMID- 11287595
TI  - Rabies virus-based vectors expressing human immunodeficiency virus type 1 (HIV-1)
      envelope protein induce a strong, cross-reactive cytotoxic T-lymphocyte response
      against envelope proteins from different HIV-1 isolates.
AB  - Novel viral vectors that are able to induce both strong and long-lasting immune
      responses may be required as effective vaccines for human immunodeficiency virus
      type 1 (HIV-1) infection. Our previous experiments with a replication-competent
      vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from a
      laboratory-adapted HIV-1 strain (NL4-3) and a primary HIV-1 isolate (89.6) showed
      that RV-based vectors are excellent for B-cell priming. Here we report that
      cytotoxic T-lymphocyte (CTL) responses against HIV-1 gp160 are induced by
      recombinant RVs. Our results indicated that a single inoculation of mice with an
      RV expressing HIV-1 gp160 induced a solid and long-lasting memory CTL response
      specific for HIV-1 envelope protein. Moreover, CTLs from immunized mice were not
      restricted to the homologous HIV-1 envelope protein and were able to cross-kill
      target cells expressing HIV-1 gp160 from heterologous HIV-1 strains. These
      studies further suggest promise for RV-based vectors to elicit a persistent
      immune response against HIV-1 and their potential utility as efficacious anti-HIV
      1 vaccines.

PMID- 11287597
TI  - Generation of a highly pathogenic avian influenza A virus from an avirulent field
      isolate by passaging in chickens.
AB  - Highly virulent avian influenza viruses can arise from avirulent strains
      maintained in poultry, but evidence to support their generation from viruses in
      wild birds is lacking. The most likely mechanism for the acquisition of virulence
      by benign avian viruses is the introduction of mutations by error-prone RNA
      polymerase, followed by the selection of virulent viruses. To investigate whether
      this mechanism could apply to wild waterfowl, we studied an avirulent wild-swan
      virus that replicates poorly in chickens. After 24 consecutive passages by air
      sac inoculation, followed by five passages in chicken brain, the avirulent virus
      became highly pathogenic in chickens, producing a 100% mortality rate. Sequence
      analysis at the hemmaglutinin cleavage site of the original isolate revealed a
      typical avirulence type of sequence, R-E-T-R, which progressed incrementally to a
      typical virulence type of sequence, R-R-K-K-R, during repeated passages in
      chickens. These results demonstrate that avirulent viruses maintained in wild
      waterfowl in nature and bearing the consensus avirulence type sequence R-E-T-R
      have the potential to become highly pathogenic while circulating in chickens.

PMID- 11287598
TI  - Selection of apoptosis-deficient adenovirus E4orf4 mutants in Saccharomyces
      cerevisiae.
AB  - Adenovirus E4orf4 protein has been shown to induce p53-independent, protein
      phosphatase 2A (PP2A)-dependent apoptosis in transformed cells. Furthermore,
      E4orf4 also induces toxicity in Saccharomyces cerevisiae in a PP2A-dependent
      manner (D. Kornitzer and T. Kleinberger, submitted for publication). In this
      work, we utilized yeast cells to select for nonapoptotic E4orf4 mutants which, in
      turn, were shown to possess a diminished ability to bind PP2A. The success of
      this selection system will provide additional apoptosis-relevant mutants for
      E4orf4 research and strongly supports the relevance of E4orf4-induced toxicity in
      S. cerevisiae to E4orf4-induced apoptosis in mammalian cells.

PMID- 11287599
TI  - Macaques with rapid disease progression and simian immunodeficiency virus
      encephalitis have a unique cytokine profile in peripheral lymphoid tissues.
AB  - The influence of host cytokine response on viral load, disease progression, and
      neurologic lesions was investigated in the simian immunodeficiency virus (SIV)
      infected macaque model of AIDS. Cytokine gene expression (interleukin-1beta [IL
      1beta], IL-2, IL-6, IL-10, gamma interferon [IFN-gamma], and tumor necrosis
      factor alpha [TNF-alpha]) and viral loads were evaluated by semiquantitative
      reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals
      infected with SIVmac251 at the terminal stages of AIDS. Infected animals showed
      higher expression of IFN-gamma, IL-6, and IL-10 mRNAs compared with controls.
      Levels of all cytokines were comparable between animals with rapid (survival,
      <200 days) or slow/normal (survival, >200 days) disease progression. However,
      among rapid progressors, the eight animals with SIV encephalitis had a unique
      cytokine profile (increased IL-2, IL-6, and IFN-gamma) that was associated with
      higher viral loads. These observations provide evidence that host cytokine
      responses may influence SIV neuropathogenesis independent of disease progression.

PMID- 11287600
TI  - Inhibition of host transcription by vesicular stomatitis virus involves a novel
      mechanism that is independent of phosphorylation of TATA-binding protein (TBP) or
      association of TBP with TBP-associated factor subunits.
AB  - The matrix (M) protein of vesicular stomatitis virus (VSV) is a potent inhibitor
      in vivo of transcription by all three host RNA polymerases (RNAP). In the case of
      host RNA polymerase II (RNAPII), the inhibition is due to lack of activity of the
      TATA-binding protein (TBP), which is a subunit of the basal transcription factor
      TFIID. Despite the potency of M protein-induced inhibition in vivo, experiments
      presented here show that M protein cannot directly inactivate TFIID in vitro.
      Addition of M protein to nuclear extracts from uninfected cells did not inhibit
      transcription activity, indicating that the inhibition is indirect and is
      mediated through host factors. The host factors that are known to regulate TBP
      activity include phosphorylation by host kinases and association with different
      TBP-associated factor (TAF) subunits. However, TBP in VSV-infected cells was
      found to be assembled normally with its TAF subunits, as shown by ion exchange
      high-pressure liquid chromatography and sedimentation velocity analysis. A normal
      pattern of phosphorylation of TBP in VSV-infected cells was also observed by pH
      gradient gel electrophoresis. Collectively, these data indicate that M protein
      inactivates TBP activity in RNAPII-dependent transcription by a novel mechanism,
      since the known mechanisms for regulating TBP activity cannot account for the
      inhibition.

PMID- 11287601
TI  - Human papillomavirus type 16 E6-induced degradation of E6TP1 correlates with its
      ability to immortalize human mammary epithelial cells.
AB  - Recent analyses have identified a number of binding partners for E6, including
      E6AP, ERC55, paxillin, hDlg, p300, interferon regulatory factor 3, hMCM7, Bak,
      and E6TP1. Notably, association with E6 targets p53, E6TP1, myc, hMCM7, and Bak
      for degradation. However, the relative importance of the various E6 targets in
      cellular transformation remains unclear. E6 alone can dominantly immortalize
      normal human mammary epithelial cells (MECs), permitting an assessment of the
      importance of various E6 targets in cellular transformation. Studies in this
      system indicate that E6-induced degradation of p53 and E6 binding to ERC55 or
      hDlg do not correlate with efficient immortalization. Here, we have examined the
      role of E6TP1, a Rap GTPase-activating protein, in E6-induced immortalization of
      MECs. We tested a large set of human papillomavirus type 16 E6 mutants for their
      ability to bind and target E6TP1 for degradation in vitro and in vivo. We
      observed a strict correlation between the ability of E6 protein to target E6TP1
      for degradation and its ability to immortalize MECs. Recent studies have
      identified telomerase as a target of E6 protein. Previous analyses of E6 mutants
      have revealed this trait to closely correlate with MEC immortalization. We
      examined our entire panel of E6 mutants for rapid induction of telomerase
      activity and found in general a strong correlation with immortalizing ability.
      The tight correlation between E6TP1 degradation and MEC immortalization strongly
      supports a critical role of functional inactivation of E6TP1 in E6-induced
      cellular immortalization.

PMID- 11287602
TI  - Transcriptional activation of the telomerase hTERT gene by human papillomavirus
      type 16 E6 oncoprotein.
AB  - The E6 and E7 oncogenes of human papillomavirus type 16 (HPV-16) are sufficient
      for the immortalization of human genital keratinocytes in vitro. The products of
      these viral genes associate with p53 and pRb tumor suppressor proteins,
      respectively, and interfere with their normal growth-regulatory functions. The
      HPV-16 E6 protein has also been shown to increase the telomerase enzyme activity
      in primary epithelial cells by an unknown mechanism. We report here that a study
      using reverse transcription-PCR and RNase protection assays in transduced primary
      human foreskin keratinocytes (HFKs) shows that the E6 gene (but not the E7 gene)
      increases telomerase hTERT gene transcription coordinately with E6-induced
      telomerase activity. In these same cells, the E6 gene induces a 6.5-fold increase
      in the activity of a 1,165-bp 5' promoter/regulatory region of the hTERT gene,
      and this induction is attributable to a minimal 251-bp sequence (-211 to +40).
      Furthermore, there is a 35-bp region (+5 to +40) within this minimal E6
      responsive promoter that is responsible for 60% of E6 activity. Although the
      minimal hTERT promoter contains Myc-responsive E-box elements and recent studies
      have suggested a role for Myc protein in hTERT transcriptional control, we found
      no alterations in the abundance of either c-Myc or c-Mad in E6-transduced HFKs,
      suggesting that there are other or additional transcription factors critical for
      regulating hTERT expression.

PMID- 11287603
TI  - Sequences flanking hypersensitive sites of the beta-globin locus control region
      are required for synergistic enhancement.
AB  - The major distal regulatory sequence for the beta-globin gene locus, the locus
      control region (LCR), is composed of multiple hypersensitive sites (HSs).
      Different models for LCR function postulate that the HSs act either independently
      or synergistically. To test these possibilities, we have constructed a series of
      expression cassettes in which the gene encoding the enhanced green fluorescent
      protein (EGFP) is under the control of DNA fragments containing single and
      multiple HSs of the LCR. LCR DNA fragments containing only the minimal region
      needed for position-independent expression (HS cores) or containing cores plus
      flanking sequences (HS units) were compared to ascertain whether conserved
      sequences between the HS cores contributed to enhancement. Expression of these
      constructs was measured after targeted integration into three defined loci in
      murine erythroleukemia cells using recombinase-mediated cassette exchange. At all
      three marked loci, synergistic enhancement of expression was observed in
      cassettes containing a combination of HS2, HS3, and HS4 units. In contrast, HS2,
      HS3, and HS4 cores (without flanking sequences) give an activity equivalent to
      the sum of the activities of the individual HS cores. These data suggest a model
      in which an HS core plus flanking regions, bound by specific proteins, forms a
      structure needed for interaction with other HS units to confer strong enhancement
      by the LCR. The three targeted integration sites differ substantially in their
      permissivity for expression, but even the largest LCR construct tested could not
      overcome these position effects to confer equal expression at all three sites.

PMID- 11287604
TI  - Phosphorylation of nuclear phospholipase C beta1 by extracellular signal
      regulated kinase mediates the mitogenic action of insulin-like growth factor I.
AB  - It is well established that a phosphoinositide (PI) cycle which is operationally
      distinct from the classical plasma membrane PI cycle exists within the nucleus,
      where it is involved in both cell proliferation and differentiation. However,
      little is known about the regulation of the nuclear PI cycle. Here, we report
      that nucleus-localized phospholipase C (PLC) beta1, the key enzyme for the
      initiation of this cycle, is a physiological target of extracellular signal
      regulated kinase (ERK). Stimulation of Swiss 3T3 cells with insulin-like growth
      factor I (IGF-I) caused rapid nuclear translocation of activated ERK and
      concurrently induced phosphorylation of nuclear PLC beta1, which was completely
      blocked by the MEK inhibitor PD 98059. Coimmunoprecipitation detected a specific
      association between the activated ERK and PLC beta1 within the nucleus. In vitro
      studies revealed that recombinant PLC beta1 could be efficiently phosphorylated
      by activated mitogen-activated protein kinase but not by PKA. The ERK
      phosphorylation site was mapped to serine 982, which lies within a PSSP motif
      located in the characteristic carboxy-terminal tail of PLC beta1. In cells
      overexpressing a PLC beta1 mutant in which serine 982 is replaced by glycine
      (S982G), IGF-I failed to activate the nuclear PI cycle, and its mitogenic effect
      was also markedly attenuated. Expression of S982G was found to inhibit ERK
      mediated phosphorylation of endogenous PLC beta1. This result suggests that ERK
      evoked phosphorylation of PLC beta1 at serine 982 plays a critical role in the
      activation of the nuclear PI cycle and is also crucial to the mitogenic action of
      IGF-I.

PMID- 11287605
TI  - Identification of liver X receptor-retinoid X receptor as an activator of the
      sterol regulatory element-binding protein 1c gene promoter.
AB  - In an attempt to identify transcription factors which activate sterol-regulatory
      element-binding protein 1c (SREBP-1c) transcription, we screened an expression
      cDNA library from adipose tissue of SREBP-1 knockout mice using a reporter gene
      containing the 2.6-kb mouse SREBP-1 gene promoter. We cloned and identified the
      oxysterol receptors liver X receptor (LXRalpha) and LXRbeta as strong activators
      of the mouse SREBP-1c promoter. In the transfection studies, expression of either
      LXRalpha or -beta activated the SREBP-1c promoter-luciferase gene in a dose
      dependent manner. Deletion and mutation studies, as well as gel mobility shift
      assays, located an LXR response element complex consisting of two new LXR-binding
      motifs which showed high similarity to an LXR response element recently found in
      the ABC1 gene promoter, a reverse cholesterol transporter. Addition of an LXR
      ligand, 22(R)-hydroxycholesterol, increased the promoter activity. Coexpression
      of retinoid X receptor (RXR), a heterodimeric partner, and its ligand 9-cis
      retinoic acid also synergistically activated the SREBP-1c promoter. In HepG2
      cells, SREBP-1c mRNA and precursor protein levels were induced by treatment with
      22(R)-hydroxycholesterol and 9-cis-retinoic acid, confirming that endogenous LXR
      RXR activation can induce endogenous SREBP-1c expression. The activation of SREBP
      1c by LXR is associated with a slight increase in nuclear SREBP-1c, resulting in
      activation of the gene for fatty acid synthase, one of its downstream genes, as
      measured by the luciferase assay. These data demonstrate that LXR-RXR can modify
      the expression of genes for lipogenic enzymes by regulating SREBP-1c expression,
      providing a novel link between fatty acid and cholesterol metabolism.

PMID- 11287606
TI  - Two distinct domains within CIITA mediate self-association: involvement of the
      GTP-binding and leucine-rich repeat domains.
AB  - CIITA is the master regulator of class II major histocompatibility complex gene
      expression. We present evidence that CIITA can self-associate via two domains:
      the C terminus (amino acids 700 to 1130) and the GTP-binding domain (amino acids
      336 to 702). Heterotypic and homotypic interactions are observed between these
      two regions. Deletions within the GTP-binding domain that reduce GTP-binding and
      transactivation function also reduce self-association. In addition, two leucine
      residues in the C-terminal leucine-rich repeat region are critical for self
      association as well as function. This study reveals for the first time a complex
      pattern of CIITA self-association. These interactions are discussed with regard
      to the apoptosis signaling proteins, Apaf-1 and Nod1, which share domain
      arrangements similar to those of CIITA.

PMID- 11287608
TI  - Caspase cleavage enhances the apoptosis-inducing effects of BAD.
AB  - The function of BAD, a proapoptotic member of the Bcl-2 family, is regulated
      primarily by rapid changes in phosphorylation that modulate its protein-protein
      interactions and subcellular localization. We show here that, during interleukin
      3 (IL-3) deprivation-induced apoptosis of 32Dcl3 murine myeloid precursor cells,
      BAD is cleaved by a caspase(s) at its N terminus to generate a 15-kDa truncated
      protein. The 15-kDa truncated BAD is a more potent inducer of apoptosis than the
      wild-type protein, whereas a mutant BAD resistant to caspase 3 cleavage is a weak
      apoptosis inducer. Truncated BAD is detectable only in the mitochondrial
      fraction, interacts with BCL-X(L) at least as effectively as the wild-type
      protein, and is more potent than wild-type BAD in inducing cytochrome c release.
      Human BAD, which is 43 amino acids shorter than its mouse counterpart, is also
      cleaved by a caspase(s) upon exposure of Jurkat T cells to anti-FAS antibody,
      tumor necrosis factor alpha (TNF-alpha), or TRAIL. Moreover, a truncated form of
      human BAD lacking the N-terminal 28 amino acids is more potent than wild-type BAD
      in inducing apoptosis. The generation of truncated BAD was blocked by Bcl-2 in IL
      3-deprived 32Dcl3 cells but not in Jurkat T cells exposed to anti-FAS antibody,
      TNF-alpha, or TRAIL. Together, these findings point to a novel and important role
      for BAD in maintaining the apoptotic phenotype in response to various apoptosis
      inducers.

PMID- 11287607
TI  - AP-1 repressor protein JDP-2: inhibition of UV-mediated apoptosis through p53
      down-regulation.
AB  - Members of the AP-1 transcription factor family, especially c-Jun and c-Fos, have
      long been known to mediate critical steps in the cellular response to ultraviolet
      (UV) irradiation. We sought to examine whether two newly discovered members of
      the AP-1 family, JDP-1 and JDP-2, also participate in the mammalian UV response.
      Here we report that JDP-2, but not JDP-1, is transiently induced upon UV
      challenge and that elevated levels of JDP-2 increase cell survival following UV
      exposure. This protective function of JDP-2 appears to be mediated through
      repression of p53 expression at the transcriptional level, via a conserved
      atypical AP-1 site in the p53 promoter.

PMID- 11287609
TI  - A novel yeast U2 snRNP protein, Snu17p, is required for the first catalytic step
      of splicing and for progression of spliceosome assembly.
AB  - We have isolated and microsequenced Snu17p, a novel yeast protein with a
      predicted molecular mass of 17 kDa that contains an RNA recognition motif. We
      demonstrate that Snu17p binds specifically to the U2 small nuclear
      ribonucleoprotein (snRNP) and that it is part of the spliceosome, since the pre
      mRNA and the lariat-exon 2 are specifically coprecipitated with Snu17p. Although
      the SNU17 gene is not essential, its knockout leads to a slow-growth phenotype
      and to a pre-mRNA splicing defect in vivo. In addition, the first step of
      splicing is dramatically decreased in extracts prepared from the snu17 deletion
      (snu17Delta) mutant. This defect is efficiently reversed by the addition of
      recombinant Snu17p. To investigate the step of spliceosome assembly at which
      Snu17p acts, we have used nondenaturing gel electrophoresis. In Snu17p-deficient
      extracts, the spliceosome runs as a single slowly migrating complex. In wild-type
      extracts, usually at least two distinct complexes are observed: the
      prespliceosome, or B complex, containing the U2 but not the U1 snRNP, and the
      catalytically active spliceosome, or A complex, containing the U2, U6, and U5
      snRNPs. Northern blot analysis and affinity purification of the snu17Delta
      spliceosome showed that it contains the U1, U2, U6, U5, and U4 snRNPs. The
      unexpected stabilization of the U1 snRNP and the lack of dissociation of the U4
      snRNP suggest that loss of Snu17p inhibits the progression of spliceosome
      assembly prior to U1 snRNP release and after [U4/U6.U5] tri-snRNP addition.

PMID- 11287610
TI  - Scaffolding protein Gab2 mediates differentiation signaling downstream of Fms
      receptor tyrosine kinase.
AB  - Fms is the receptor for macrophage colony-stimulating factor (M-CSF) and contains
      intrinsic tyrosine kinase activity. Expression of exogenous Fms in a murine
      myeloid progenitor cell line, FDC-P1 (FD-Fms), results in M-CSF-dependent growth
      and macrophage differentiation. Previously, we described a 100-kDa protein that
      was tyrosine phosphorylated upon M-CSF stimulation of FD-Fms cells. In this
      report, we identify this 100-kDa protein as the recently cloned scaffolding
      protein Gab2, and we demonstrate that Gab2 associates with several molecules
      involved in M-CSF signaling, including Grb2, SHP2, the p85 subunit of
      phosphatidylinositol 3'-kinase, SHIP, and SHC. Tyrosine phosphorylation of Gab2
      in response to M-CSF requires the kinase activity of Fms, but not that of Src.
      Overexpression of Gab2 in FD-Fms cells enhanced both mitogen-activated protein
      kinase (MAPK) activity and macrophage differentiation, but reduced proliferation,
      in response to M-CSF. In contrast, a mutant of Gab2 that is unable to bind SHP2
      did not potentiate MAPK activity. Furthermore, overexpression of this mutant in
      FD-Fms cells inhibited macrophage differentiation and resulted in a concomitant
      increase in growth potential in response to M-CSF. These data indicate that Gab2
      is involved in the activation of the MAPK pathway and that the interaction
      between Gab2 and SHP2 is essential for the differentiation signal triggered by M
      CSF.

PMID- 11287613
TI  - Role of NF-Y in in vivo regulation of the gamma-globin gene.
AB  - The duplicated CCAAT box is required for gamma gene expression. We report here
      that the transcriptional factor NF-Y is recruited to the duplicated CCAAT box in
      vivo. A mutation of the duplicated CCAAT box that severely disrupts the NF-Y
      binding also reduces the accessibility level of the gamma gene promoter, affects
      the assembly of basal transcriptional machinery, and increases the recruitment of
      GATA-1 to the locus control region (LCR) and the proximal promoter and the
      recruitment of transcription cofactor CBP/p300 to the LCR. These findings suggest
      that recruitment of NF-Y to the duplicated CCAAT box plays a role in the
      chromatin opening of the gamma gene promoter as well as in the communication
      between the gamma gene promoter and the LCR.

PMID- 11287612
TI  - Negative regulation of CD4 gene expression by a HES-1-c-Myb complex.
AB  - Expression of the CD4 gene is tightly controlled throughout thymopoiesis. The
      downregulation of CD4 gene expression in CD4(-) CD8(-) and CD4(-) CD8(+) T
      lymphocytes is controlled by a transcriptional silencer located in the first
      intron of the CD4 locus. Here, we determine that the c-Myb transcription factor
      binds to a functional site in the CD4 silencer. As c-Myb is also required for CD4
      promoter function, these data indicate that depending on the context, c-Myb plays
      both positive and negative roles in the control of CD4 gene expression.
      Interestingly, a second CD4 silencer-binding factor, HES-1, binds to c-Myb in
      vivo and induces it to become a transcriptional repressor. We propose that the
      recruitment of HES-1 and c-Myb to the silencer leads to the formation of a
      multifactor complex that induces silencer function and repression of CD4 gene
      expression.

PMID- 11287611
TI  - Inhibition of cellular proliferation through IkappaB kinase-independent and
      peroxisome proliferator-activated receptor gamma-dependent repression of cyclin
      D1.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      is a ligand-regulated nuclear receptor superfamily member. Liganded PPARgamma
      exerts diverse biological effects, promoting adipocyte differentiation,
      inhibiting tumor cellular proliferation, and regulating monocyte/macrophage and
      anti-inflammatory activities in vitro. In vivo studies with PPARgamma ligands
      showed enhancement of tumor growth, raising the possibility that reduced immune
      function and tumor surveillance may outweigh the direct inhibitory effects of
      PPARgamma ligands on cellular proliferation. Recent findings that PPARgamma
      ligands convey PPARgamma-independent activities through IkappaB kinase (IKK)
      raises important questions about the specific mechanisms through which PPARgamma
      ligands inhibit cellular proliferation. We investigated the mechanisms regulating
      the antiproliferative effect of PPARgamma. Herein PPARgamma, liganded by either
      natural (15d-PGJ(2) and PGD(2)) or synthetic ligands (BRL49653 and troglitazone),
      selectively inhibited expression of the cyclin D1 gene. The inhibition of S-phase
      entry and activity of the cyclin D1-dependent serine-threonine kinase (Cdk) by
      15d-PGJ(2) was not observed in PPARgamma-deficient cells. Cyclin D1
      overexpression reversed the S-phase inhibition by 15d-PGJ(2). Cyclin D1
      repression was independent of IKK, as prostaglandins (PGs) which bound PPARgamma
      but lacked the IKK interactive cyclopentone ring carbonyl group repressed cyclin
      D1. Cyclin D1 repression by PPARgamma involved competition for limiting abundance
      of p300, directed through a c-Fos binding site of the cyclin D1 promoter. 15d
      PGJ(2) enhanced recruitment of p300 to PPARgamma but reduced binding to c-Fos.
      The identification of distinct pathways through which eicosanoids regulate anti
      inflammatory and antiproliferative effects may improve the utility of COX2
      inhibitors.

PMID- 11287614
TI  - High-mobility-group proteins NHP6A and NHP6B participate in activation of the RNA
      polymerase III SNR6 gene.
AB  - Transcription of yeast class III genes involves the formation of a transcription
      initiation complex that comprises RNA polymerase III (Pol III) and the general
      transcription factors TFIIIB and TFIIIC. Using a genetic screen for positive
      regulators able to compensate for a deficiency in a promoter element of the SNR6
      gene, we isolated the NHP6A and NHP6B genes. Here we show that the high-mobility
      group proteins NHP6A and NHP6B are required for the efficient transcription of
      the SNR6 gene both in vivo and in vitro. The transcripts of wild-type and
      promoter-defective SNR6 genes decreased or became undetectable in an nhp6ADelta
      nhp6BDelta double-mutant strain, and the protection over the TATA box of the wild
      type SNR6 gene was lost in nhp6ADelta nhp6BDelta cells at 37 degrees C. In vitro,
      NHP6B specifically stimulated the transcription of SNR6 templates up to fivefold
      in transcription assays using either cell nuclear extracts from nhp6ADelta
      nhp6BDelta cells or reconstituted transcription systems. Finally, NHP6B activated
      SNR6 transcription in a TFIIIC-independent assay. These results indicate that
      besides the general transcription factors TFIIIB and TFIIIC, additional auxillary
      factors are required for the optimal transcription of at least some specific Pol
      III genes.

PMID- 11287615
TI  - Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of
      the SNARE Snc1p in yeast.
AB  - Skp1p-cullin-F-box protein (SCF) complexes are ubiquitin-ligases composed of a
      core complex including Skp1p, Cdc53p, Hrt1p, the E2 enzyme Cdc34p, and one of
      multiple F-box proteins which are thought to provide substrate specificity to the
      complex. Here we show that the F-box protein Rcy1p is required for recycling of
      the v-SNARE Snc1p in Saccharomyces cerevisiae. Rcy1p localized to areas of
      polarized growth, and this polarized localization required its CAAX box and an
      intact actin cytoskeleton. Rcy1p interacted with Skp1p in vivo in an F-box
      dependent manner, and both deletion of its F box and loss of Skp1p function
      impaired recycling. In contrast, cells deficient in Cdc53p, Hrt1p, or Cdc34p did
      not exhibit recycling defects. Unlike the case for F-box proteins that are known
      to participate in SCF complexes, degradation of Rcy1p required neither its F box
      nor functional 26S proteasomes or other SCF core subunits. Importantly, Skp1p was
      the only major partner that copurified with Rcy1p. Our results thus suggest that
      a complex composed of Rcy1p and Skp1p but not other SCF components may play a
      direct role in recycling of internalized proteins.

PMID- 11287616
TI  - Unanticipated repression function linked to erythroid Kruppel-like factor.
AB  - The erythroid cell-specific transcription factor erythroid Kruppel-like factor
      (EKLF) is an important activator of beta-globin gene expression. It achieves this
      by binding to the CACCC element at the beta-globin promoter via its zinc finger
      domain. The coactivators CBP and P300 interact with, acetylate, and enhance its
      activity, helping to explain its role as a transcription activator. Here we show
      that EKLF can also interact with the corepressors mSin3A and HDAC1 (histone
      deacetylase 1) through its zinc finger domain. When linked to a GAL4 DNA binding
      domain, full-length EKLF or its zinc finger domain alone can repress
      transcription in vivo. This repressive activity can be relieved by the HDAC
      inhibitor trichostatin A. Although recruitment of EKLF to a promoter is required
      to show repression, its zinc finger domain cannot bind directly to DNA and
      repress transcription simultaneously. In addition, the target promoter
      configuration is important for enabling EKLF to exhibit any repressive activity.
      These results suggest that EKLF may function in vivo as a transcription repressor
      and play a previously unsuspected additional role in regulating erythroid gene
      expression and differentiation.

PMID- 11287617
TI  - Vav-Rac1-mediated activation of the c-Jun N-terminal kinase/c-Jun/AP-1 pathway
      plays a major role in stimulation of the distal NFAT site in the interleukin-2
      gene promoter.
AB  - Vav, a hematopoiesis-specific signaling protein, plays an important role in T
      cell development and activation. Vav upregulates the expression of the
      interleukin-2 (IL-2) gene, primarily via activation of the distal NFAT site in
      the IL-2 gene promoter (NFAT-IL-2). However, since this site cooperatively binds
      NFAT and AP-1, the relative contribution of Vav to NFAT versus AP-1 activation
      has not been determined. Here, we studied the respective roles of the AP-1 and
      NFAT pathways in the T-cell receptor (TCR)-mediated, Vav-dependent activation of
      NFAT-IL-2. Although Vav stimulated the transcriptional activity of an NFAT-IL-2
      reporter gene, it failed to stimulate the transcriptional or DNA-binding
      activities of an AP-1-independent NFAT site derived from the human gamma
      interferon gene promoter. Vav also did not stimulate detectable Ca(2+)
      mobilization and nuclear translocation of NFATc or NFATp. On the other hand, Vav
      induced the activation of Rac1 or Cdc42 and c-Jun N-terminal kinase (JNK),
      enhanced the transcriptional and DNA-binding activities of AP-1, and induced
      increased phosphorylation of c-Jun. Dominant-negative Vav and/or Rac1 mutants
      blocked the TCR-mediated stimulation of these events, demonstrating the
      physiological relevance of these effects. Vav also associated with Rac1 or Cdc42
      in T cells, and anti-CD3 antibody stimulation enhanced this association. These
      findings indicate that a Rac1-dependent JNK/c-Jun/AP-1 pathway, rather than the
      Ca(2+)/NFAT pathway, plays the predominant role in NFAT-IL-2 activation by Vav.

PMID- 11287618
TI  - Gadd45gamma is dispensable for normal mouse development and T-cell proliferation.
AB  - Gadd45gamma, a family member of the growth arrest and DNA damage-inducible gene
      family 45 (Gadd45), is strongly induced by interleukin-2 (IL-2) in peripheral T
      cells. While in most tissues all Gadd45 family members are expressed, Gadd45gamma
      is the only member that is induced by IL-2. Here we show that the IL-2-induced
      expression of Gadd45gamma is dependent on a signaling pathway mediated by the
      tyrosine kinase Jak3 and the transcription factors Stat5a and Stat5b (signal
      transducer and activator of transcription). Previous studies with ectopically
      overexpressed Gadd45gamma in various cell lines implicated its function in
      negative growth control. To analyze the physiological role of Gadd45gamma we used
      homologous recombination to generate mice lacking Gadd45gamma. Gadd45gamma
      deficient mice develop normally, are indistinguishable from their littermates,
      and are fertile. Furthermore, hematopoiesis in mice lacking Gadd45gamma is not
      impaired and Gadd45gamma-deficient T lymphocytes show normal responses to IL-2.
      These data demonstrate that Gadd45gamma is not essential for normal mouse
      development and hematopoiesis, possibly due to functional redundancy among the
      Gadd45 family members. Gadd45gamma is also dispensable for IL-2-induced T-cell
      proliferation.

PMID- 11287620
TI  - Generation and analysis of mice lacking the chemokine fractalkine.
AB  - Fractalkine (CX(3)CL1) is the first described chemokine that can exist either as
      a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can
      mediate adhesion of cells expressing its receptor, CX(3)CR1. This activity,
      together with its expression on endothelial cells, suggests that fractalkine
      might mediate adhesion of leukocytes to the endothelium during inflammation.
      Fractalkine is also highly expressed in neurons, and its receptor, CX(3)CR1, is
      expressed on glial cells. To determine the biologic role of fractalkine, we used
      targeted gene disruption to generate fractalkine-deficient mice. These mice did
      not exhibit overt behavioral abnormalities, and histologic analysis of their
      brains did not reveal any gross changes compared to wild-type mice. In addition,
      these mice had normal hematologic profiles except for a decrease in the number of
      blood leukocytes expressing the cell surface marker F4/80. The cellular
      composition of their lymph nodes did not differ significantly from that of wild
      type mice. Similarly, the responses of fractalkine(-/-) mice to a variety of
      inflammatory stimuli were indistinguishable from those of wild-type mice.

PMID- 11287619
TI  - Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid
      cohesion.
AB  - CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both
      exhibit genetic and physical ties to replication fork constituents. We find that
      absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and
      leads to a preanaphase accumulation of cells that depends on the spindle assembly
      checkpoint. The physical and genetic interactions between CTF4, CTF18, and core
      components of replication fork complexes observed in this study and others
      suggest that both gene products act in association with the replication fork to
      facilitate sister chromatid cohesion. We find that Ctf18p, an RFC1-like protein,
      directly interacts with Rfc2p, Rfc3p, Rfc4p, and Rfc5p. However, Ctf18p is not a
      component of biochemically purified proliferating cell nuclear antigen loading RF
      C, suggesting the presence of a discrete complex containing Ctf18p, Rfc2p, Rfc3p,
      Rfc4p, and Rfc5p. Recent identification and characterization of the budding yeast
      polymerase kappa, encoded by TRF4, strongly supports a hypothesis that the DNA
      replication machinery is required for proper sister chromatid cohesion. Analogous
      to the polymerase switching role of the bacterial and human RF-C complexes, we
      propose that budding yeast RF-C(CTF18) may be involved in a polymerase switch
      event that facilities sister chromatid cohesion. The requirement for CTF4 and
      CTF18 in robust cohesion identifies novel roles for replication accessory
      proteins in this process.

PMID- 11287621
TI  - RNA polymerase III transcription complexes on chromosomal 5S rRNA genes in vivo:
      TFIIIB occupancy and promoter opening.
AB  - Quantitative analysis of multiple-hit potassium permanganate (KMnO(4))
      footprinting has been carried out in vivo on Saccharomyces cerevisiae 5S rRNA
      genes. The results fix the number of open complexes at steady state in
      exponentially growing cells at between 8 and 17% of the 150 to 200 chromosomal
      copies. UV and dimethyl sulfate footprinting set the transcription factor TFIIIB
      occupancy at 23 to 47%. The comparison between the two values suggests that RNA
      polymerase III binding or promoter opening is the rate-limiting step in 5S rRNA
      transcription in vivo. Inhibition of RNA elongation in vivo by cordycepin
      confirms this result. An experimental system that is capable of providing
      information on the mechanistic steps involved in regulatory events in S.
      cerevisiae cells has been established.

PMID- 11287622
TI  - Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans is an opportunistic fungal pathogen that infects the
      human central nervous system. This pathogen elaborates two specialized virulence
      factors: the antioxidant melanin and an antiphagocytic immunosuppressive
      polysaccharide capsule. A signaling cascade controlling mating and virulence was
      identified. The PKA1 gene encoding the major cyclic AMP (cAMP)-dependent protein
      kinase catalytic subunit was identified and disrupted. pka1 mutant strains were
      sterile, failed to produce melanin or capsule, and were avirulent. The PKR1 gene
      encoding the protein kinase A (PKA) regulatory subunit was also identified and
      disrupted. pkr1 mutant strains overproduced capsule and were hypervirulent in
      animal models of cryptococcosis. pkr1 pka1 double mutant strains exhibited
      phenotypes similar to that of pka1 mutants, providing epistasis evidence that the
      Pka1 catalytic subunit functions downstream of the Pkr1 regulatory subunit. The
      PKA pathway was also shown to function downstream of the Galpha protein Gpa1 and
      to regulate cAMP production by feedback inhibition. These findings define a
      Galpha protein-cAMP-PKA signaling pathway regulating differentiation and
      virulence of a human fungal pathogen.

PMID- 11287624
TI  - Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1)
      protein kinase.
AB  - Emk is a serine/threonine protein kinase implicated in regulating polarity, cell
      cycle progression, and microtubule dynamics. To delineate the role of Emk in
      development and adult tissues, mice lacking Emk were generated by targeted gene
      disruption. Emk(-/-) mice displayed growth retardation and immune cell
      dysfunction. Although B- and T-cell development were normal, CD4(+)T cells
      lacking Emk exhibited a marked upregulation of the memory marker CD44/pgp-1 and
      produced more gamma interferon and interleukin-4 on stimulation through the T
      cell receptor in vitro. In addition, B-cell responses to T-cell-dependent and 
      independent antigen challenge were altered in vivo. As Emk(-/-) animals aged,
      they developed splenomegaly, lymphadenopathy, membranoproliferative
      glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and
      kidneys. Taken together, these results demonstrate that the Emk protein kinase is
      essential for maintaining immune system homeostasis and that loss of Emk may
      contribute to autoimmune disease in mammals.

PMID- 11287623
TI  - Induction of beta3-integrin gene expression by sustained activation of the Ras
      regulated Raf-MEK-extracellular signal-regulated kinase signaling pathway.
AB  - Alterations in the expression of integrin receptors for extracellular matrix
      (ECM) proteins are strongly associated with the acquisition of invasive and/or
      metastatic properties by human cancer cells. Despite this, comparatively little
      is known of the biochemical mechanisms that regulate the expression of integrin
      genes in cells. Here we demonstrate that the Ras-activated Raf-MEK-extracellular
      signal-regulated kinase (ERK) signaling pathway can specifically control the
      expression of individual integrin subunits in a variety of human and mouse cell
      lines. Pharmacological inhibition of MEK1 in a number of human melanoma and
      pancreatic carcinoma cell lines led to reduced cell surface expression of alpha6-
      and beta3-integrin. Consistent with this, conditional activation of the Raf-MEK
      ERK pathway in NIH 3T3 cells led to a 5 to 20-fold induction of cell surface
      alpha6- and beta3-integrin expression. Induced beta3-integrin was expressed on
      the cell surface as a heterodimer with alphav-integrin; however, the overall
      level of alphav-integrin expression was not altered by Ras or Raf. Raf-induced
      beta3-integrin was observed in primary and established mouse fibroblast lines and
      in mouse and human endothelial cells. Consistent with previous reports of the
      ability of the Raf-MEK-ERK signaling pathway to induce beta3-integrin gene
      transcription in human K-562 erythroleukemia cells, Raf activation in NIH 3T3
      cells led to elevated beta3-integrin mRNA. However, unlike immediate-early Raf
      targets such as heparin binding epidermal growth factor and Mdm2, beta3-integrin
      mRNA was induced by Raf in a manner that was cycloheximide sensitive.
      Surprisingly, activation of the Raf-MEK-ERK signaling pathway by growth factors
      and mitogens had little or no effect on beta3-integrin expression, suggesting
      that the expression of this gene requires sustained activation of this signaling
      pathway. In addition, despite the robust induction of cell surface alphavbeta3
      integrin expression by Raf in NIH 3T3 cells, such cells display decreased
      spreading and adhesion, with a loss of focal adhesions and actin stress fibers.
      These data suggest that oncogene-induced alterations in integrin gene expression
      may participate in the changes in cell adhesion and migration that accompany the
      process of oncogenic transformation.

PMID- 11287625
TI  - Identification of TFII-I as the endoplasmic reticulum stress response element
      binding factor ERSF: its autoregulation by stress and interaction with ATF6.
AB  - When mammalian cells are subjected to stress targeted to the endoplasmic
      reticulum (ER), such as depletion of the ER Ca(2+) store, the transcription of a
      family of glucose-regulated protein (GRP) genes encoding ER chaperones is
      induced. The GRP promoters contain multiple copies of the ER stress response
      element (ERSE), consisting of a unique tripartite structure, CCAAT(N(9))CCACG.
      Within a subset of mammalian ERSEs, N(9) represents a GC-rich sequence of 9 bp
      that is conserved across species. A novel complex (termed ERSF) exhibits enhanced
      binding to the ERSE of the grp78 and ERp72 promoters using HeLa nuclear extracts
      prepared from ER-stressed cells. Optimal binding of ERSF to ERSE and maximal ERSE
      mediated stress inducibility require the conserved GGC motif within the 9-bp
      region. Through chromatographic purification and subsequent microsequencing, we
      have identified ERSF as TFII-I. Whereas TFII-I remains predominantly nuclear in
      both nontreated NIH 3T3 cells and cells treated with thapsigargin (Tg), a potent
      inducer of the GRP stress response through depletion of the ER Ca(2+) store, the
      level of TFII-I transcript was elevated in Tg-stressed cells, correlating with an
      increase in TFII-I protein level in the nuclei of Tg-stressed cells. Purified
      recombinant TFII-I isoforms bind directly to the ERSEs of grp78 and ERp72
      promoters. The stimulation of ERSE-mediated transcription by TFII-I requires the
      consensus tyrosine phosphorylation site of TFII-I and the GGC sequence motif of
      the ERSE. We further discovered that TFII-I is an interactive protein partner of
      ATF6 and that optimal stimulation of ERSE by ATF6 requires TFII-I.

PMID- 11287626
TI  - Hepatic nuclear factor 1-alpha directs nucleosomal hyperacetylation to its tissue
      specific transcriptional targets.
AB  - Mutations in the gene encoding hepatic nuclear factor 1-alpha (HNF1-alpha) cause
      a subtype of human diabetes resulting from selective pancreatic beta-cell
      dysfunction. We have analyzed mice lacking HNF1-alpha to study how this protein
      controls beta-cell-specific transcription in vivo. We show that HNF1-alpha is
      essential for the expression of glut2 glucose transporter and L-type pyruvate
      kinase (pklr) genes in pancreatic insulin-producing cells, whereas in liver,
      kidney, or duodenum tissue, glut2 and pklr expression is maintained in the
      absence of HNF1-alpha. HNF1-alpha nevertheless occupies the endogenous glut2 and
      pklr promoters in both pancreatic islet and liver cells. However, it is
      indispensable for hyperacetylation of histones in glut2 and pklr promoter
      nucleosomes in pancreatic islets but not in liver cells, where glut2 and pklr
      chromatin remains hyperacetylated in the absence of HNF1-alpha. In contrast, the
      phenylalanine hydroxylase promoter requires HNF1-alpha for transcriptional
      activity and localized histone hyperacetylation only in liver tissue. Thus,
      different HNF1-alpha target genes have distinct requirements for HNF1-alpha in
      either pancreatic beta-cells or liver cells. The results indicate that HNF1-alpha
      occupies target gene promoters in diverse tissues but plays an obligate role in
      transcriptional activation only in cellular- and promoter-specific contexts in
      which it is required to recruit histone acetylase activity. These findings
      provide genetic evidence based on a live mammalian system to establish that a
      single activator can be essential to direct nucleosomal hyperacetylation to
      transcriptional targets.

PMID- 11287627
TI  - Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors
      p18(Ink4c) and p19(Ink4d).
AB  - Male mice lacking both the Ink4c and Ink4d genes, which encode two inhibitors of
      D-type cyclin-dependent kinases (Cdks), are infertile, whereas female fecundity
      is unaffected. Both p18(Ink4c) and p19(Ink4d) are expressed in the seminiferous
      tubules of postnatal wild-type mice, being largely confined to postmitotic
      spermatocytes undergoing meiosis. Their combined loss is associated with the
      delayed exit of spermatogonia from the mitotic cell cycle, leading to the
      retarded appearance of meiotic cells that do not properly differentiate and
      instead undergo apoptosis at an increased frequency. As a result, mice lacking
      both Ink4c and Ink4d produce few mature sperm, and the residual spermatozoa have
      reduced motility and decreased viability. Whether or not Ink4d is present,
      animals lacking Ink4c develop hyperplasia of interstitial testicular Leydig
      cells, which produce reduced levels of testosterone. The anterior pituitary of
      fertile mice lacking Ink4c or infertile mice doubly deficient for Ink4c and Ink4d
      produces normal levels of luteinizing hormone (LH). Therefore, the failure of
      Leydig cells to produce testosterone is not secondary to defects in LH
      production, and reduced testosterone levels do not account for infertility in the
      doubly deficient strain. By contrast, Ink4d-null or double-null mice produce
      elevated levels of follicle-stimulating hormone (FSH). Because Ink4d-null mice
      are fertile, increased FSH production by the anterior pituitary is also unlikely
      to contribute to the sterility observed in Ink4c/Ink4d double-null males. Our
      data indicate that p18(Ink4c) and p19(Ink4d) are essential for male fertility.
      These two Cdk inhibitors collaborate in regulating spermatogenesis, helping to
      ensure mitotic exit and the normal meiotic maturation of spermatocytes.

PMID- 11287628
TI  - Accumulation of cyclin E is not a prerequisite for passage through the
      restriction point.
AB  - The restriction point (R) is defined as the point in G(1) after which cells can
      complete a division cycle without growth factors and divides G(1) into two
      physiologically different intervals in cycling cells, G(1)-pm (a postmitotic
      interval with a constant length of 3 to 4 h) and G(1)-ps (a pre-DNA-synthetic
      interval with a variable length of 1 to 10 h). Cyclin E is a G(1) regulatory
      protein whose accumulation has been suggested to be critical for passage through
      R. We have studied cyclin E protein levels in individual cells of asynchronously
      growing cell populations, with respect to both passage through R and entry into S
      phase. We found that the postmitotic G(1) cells that had not yet reached R were
      negative for cyclin E accumulation. On the other hand, cells that had passed R
      were found to accumulate cyclin E at variable times (1 to 8 h) after passage
      through R and 2 to 5 h before entry into S. These kinetic data rule out the
      hypothesis that passage through R is dependent on the accumulation of cyclin E
      but suggest, instead, the converse, that passage through R is a prerequisite for
      cyclin E accumulation. Furthermore, we found that most of the cyclin E protein is
      downregulated within 1 to 2 h after entry into S.

PMID- 11287629
TI  - Expression level-dependent contribution of glucocorticoid receptor domains for
      functional interaction with STAT5.
AB  - The action of the glucocorticoid receptor (GR) on beta-casein gene transcription
      serves as a well-studied example of a case where the action of the GR is
      dependent on the activity of another transcription factor, STAT5. We have
      investigated the domain-requirement of the GR for this synergistic response in
      transfection experiments employing GR mutants and CV-1 or COS-7 cells. The
      results were influenced by the expression levels of the GR constructs. At low
      expression, STAT5-dependent transactivation by mutants of the GR DNA binding
      domain or N-terminal transactivation domain was impaired and the
      antiglucocorticoid RU486 exhibited a weak agonistic activity. When the N-terminal
      region of the GR was exchanged with the respective domain of the progesterone
      receptor, STAT5-dependent transactivation was reduced at low and high expression
      levels. Only at high expression levels did the GR exhibit the properties of a
      coactivator and enhanced STAT5 activity in the absence of a functional DNA
      binding domain and of GR binding sites in the proximal region of the beta-casein
      gene promoter. Furthermore, at high GR expression levels RU486 was nearly as
      efficient as dexamethasone in activating transcription via the STAT5 dependent
      beta-casein gene promoter. The results reconcile the controversial issue
      regarding the DNA binding-independent action of the GR together with STAT5 and
      provide evidence that the mode of action of the GR depends not only on the type
      of the particular promoter at which it acts but also on the concentration of the
      GR. GR DNA binding function appears to be mandatory for beta-casein gene
      expression in mammary epithelial cells, since the promoter function is completely
      dependent on the integrity of GR binding sites in the promoter.

PMID- 11287630
TI  - A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes
      tumor necrosis factor inhibition of insulin signaling through insulin receptor
      substrate-1.
AB  - Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by the insulin
      receptor permits this docking protein to interact with signaling proteins that
      promote insulin action. Serine phosphorylation uncouples IRS-1 from the insulin
      receptor, thereby inhibiting its tyrosine phosphorylation and insulin signaling.
      For this reason, there is great interest in identifying serine/threonine kinases
      for which IRS-1 is a substrate. Tumor necrosis factor (TNF) inhibited insulin
      promoted tyrosine phosphorylation of IRS-1 and activated the Akt/protein kinase B
      serine-threonine kinase, a downstream target for phosphatidylinositol 3-kinase
      (PI 3-kinase). The effect of TNF on insulin-promoted tyrosine phosphorylation of
      IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor,
      which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas
      constitutively active Akt impaired insulin-promoted IRS-1 tyrosine
      phosphorylation. Conversely, TNF inhibition of IRS-1 tyrosine phosphorylation was
      blocked by kinase dead Akt. Inhibition of IRS-1 tyrosine phosphorylation by TNF
      was blocked by rapamycin, an inhibitor of the mammalian target of rapamycin
      (mTOR), a downstream target of Akt. mTOR induced the serine phosphorylation of
      IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin. These
      results suggest that TNF impairs insulin signaling through IRS-1 by activation of
      a PI 3-kinase/Akt/mTOR pathway, which is antagonized by PTEN.

PMID- 11287631
TI  - Fit genotypes and escape variants of subgroup III Neisseria meningitidis during
      three pandemics of epidemic meningitis.
AB  - The genetic variability at six polymorphic loci was examined within a global
      collection of 502 isolates of subgroup III, serogroup A Neisseria meningitidis.
      Nine "genoclouds" were identified, consisting of genotypes that were isolated
      repeatedly plus 48 descendent genotypes that were isolated rarely. These
      genoclouds have caused three pandemic waves of disease since the mid-1960s, the
      most recent of which was imported from East Asia to Europe and Africa in the mid
      1990s. Many of the genotypes are escape variants, resulting from positive
      selection that we attribute to herd immunity. Despite positive selection, most
      escape variants are less fit than their parents and are lost because of
      competition and bottlenecks during spread from country to country. Competition
      between fit genotypes results in dramatic changes in population composition over
      short time periods.

PMID- 11287632
TI  - Structure and function of the C-terminal PABC domain of human poly(A)-binding
      protein.
AB  - We have determined the solution structure of the C-terminal quarter of human
      poly(A)-binding protein (hPABP). The protein fragment contains a protein domain,
      PABC [for poly(A)-binding protein C-terminal domain], which is also found
      associated with the HECT family of ubiquitin ligases. By using peptides derived
      from PABP interacting protein (Paip) 1, Paip2, and eRF3, we show that PABC
      functions as a peptide binding domain. We use chemical shift perturbation
      analysis to identify the peptide binding site in PABC and the major elements
      involved in peptide recognition. From comparative sequence analysis of PABC
      binding peptides, we formulate a preliminary PABC consensus sequence and identify
      human ataxin-2, the protein responsible for type 2 spinocerebellar ataxia (SCA2),
      as a potential PABC ligand.

PMID- 11287633
TI  - Effects of temporal association on recognition memory.
AB  - The influence of temporal association on the representation and recognition of
      objects was investigated. Observers were shown sequences of novel faces in which
      the identity of the face changed as the head rotated. As a result, observers
      showed a tendency to treat the views as if they were of the same person.
      Additional experiments revealed that this was only true if the training sequences
      depicted head rotations rather than jumbled views; in other words, the sequence
      had to be spatially as well as temporally smooth. Results suggest that we are
      continuously associating views of objects to support later recognition, and that
      we do so not only on the basis of the physical similarity, but also the
      correlated appearance in time of the objects.

PMID- 11287635
TI  - Deuterium isotope effect on the intramolecular electron transfer in Pseudomonas
      aeruginosa azurin.
AB  - Intramolecular electron transfer in azurin in water and deuterium oxide has been
      studied over a broad temperature range. The kinetic deuterium isotope effect,
      k(H)/k(D), is smaller than unity (0.7 at 298 K), primarily caused by the
      different activation entropies in water (-56.5 J K(-1) mol(-1)) and in deuterium
      oxide (-35.7 J K(-1) mol(-1)). This difference suggests a role for distinct
      protein solvation in the two media, which is supported by the results of
      voltammetric measurements: the reduction potential (E(0')) of Cu(2+/+) at 298 K
      is 10 mV more positive in D(2)O than in H(2)O. The temperature dependence of
      E(0') is also different, yielding entropy changes of -57 J K(-1) mol(-1) in water
      and -84 J K(-1) mol(-1) in deuterium oxide. The driving force difference of 10 mV
      is in keeping with the kinetic isotope effect, but the contribution to DeltaS
      from the temperature dependence of E(0') is positive rather than negative.
      Isotope effects are, however, also inherent in the nuclear reorganization Gibbs
      free energy and in the tunneling factor for the electron transfer process. A
      slightly larger thermal protein expansion in H(2)O than in D(2)O (0.001 nm K(-1))
      is sufficient both to account for the activation entropy difference and to
      compensate for the different temperature dependencies of E(0'). Thus, differences
      in driving force and thermal expansion appear as the most straightforward
      rationale for the observed isotope effect.

PMID- 11287634
TI  - Genetic evidence for different male and female roles during cultural transitions
      in the British Isles.
AB  - Human history is punctuated by periods of rapid cultural change. Although
      archeologists have developed a range of models to describe cultural transitions,
      in most real examples we do not know whether the processes involved the movement
      of people or the movement of culture only. With a series of relatively well
      defined cultural transitions, the British Isles present an ideal opportunity to
      assess the demographic context of cultural change. Important transitions after
      the first Paleolithic settlements include the Neolithic, the development of Iron
      Age cultures, and various historical invasions from continental Europe. Here we
      show that patterns of Y-chromosome variation indicate that the Neolithic and Iron
      Age transitions in the British Isles occurred without large-scale male movements.
      The more recent invasions from Scandinavia, on the other hand, appear to have
      left a significant paternal genetic legacy. In contrast, patterns of mtDNA and X
      chromosome variation indicate that one or more of these pre-Anglo-Saxon cultural
      revolutions had a major effect on the maternal genetic heritage of the British
      Isles.

PMID- 11287636
TI  - Attomole level protein sequencing by Edman degradation coupled with accelerator
      mass spectrometry.
AB  - Edman degradation remains the primary method for determining the sequence of
      proteins. In this study, accelerator mass spectrometry was used to determine the
      N-terminal sequence of glutathione S-transferase at the attomole level with
      zeptomole precision using a tracer of (14)C. The transgenic transferase was
      labeled by growing transformed Escherichia coli on [(14)C]glucose and purified by
      microaffinity chromatography. An internal standard of peptides on a solid phase
      synthesized to release approximately equal amounts of all known amino acids with
      each cycle were found to increase yield of gas phase sequencing reactions and
      subsequent semimicrobore HPLC as did a lactoglobulin carrier. This method is
      applicable to the sequencing of proteins from cell culture and illustrates a path
      to more general methods for determining N-terminal sequences with high
      sensitivity.

PMID- 11287637
TI  - Structures of two molluscan hemocyanin genes: significance for gene evolution.
AB  - We present here the description of genes coding for molluscan hemocyanins. Two
      distantly related mollusks, Haliotis tuberculata and Octopus dofleini, were
      studied. The typical architecture of a molluscan hemocyanin subunit, which is a
      string of seven or eight globular functional units (FUs, designated a to h, about
      50 kDa each), is reflected by the gene organization: a series of eight
      structurally related coding regions in Haliotis, corresponding to FU-a to FU-h,
      with seven highly variable linker introns of 174 to 3,198 bp length (all in phase
      1). In Octopus seven coding regions (FU-a to FU-g) are found, separated by phase
      1 introns varying in length from 100 bp to 910 bp. Both genes exhibit typical
      signal (export) sequences, and in both cases these are interrupted by an
      additional intron. Each gene also contains an intron between signal peptide and
      FU-a and in the 3' untranslated region. Of special relevance for evolutionary
      considerations are introns interrupting those regions that encode a discrete
      functional unit. We found that five of the eight FUs in Haliotis each are encoded
      by a single exon, whereas FU-f, FU-g, and FU-a are encoded by two, three and four
      exons, respectively. Similarly, in Octopus four of the FUs each correspond to an
      uninterrupted exon, whereas FU-b, FU-e, and FU-f each contain a single intron.
      Although the positioning of the introns between FUs is highly conserved in the
      two mollusks, the introns within FUs show no relationship either in location nor
      phase. It is proposed that the introns between FUs were generated as the eight
      unit polypeptide evolved from a monomeric precursor, and that the internal
      introns have been added later. A hypothesis for evolution of the ring-like
      quaternary structure of molluscan hemocyanins is presented.

PMID- 11287638
TI  - Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside
      phosphorylase, selectively inhibits human T lymphocytes.
AB  - Transition-state theory has led to the design of Immucillin-H (Imm-H), a
      picomolar inhibitor of purine nucleoside phosphorylase (PNP). In humans, PNP is
      the only route for degradation of deoxyguanosine, and genetic deficiency of this
      enzyme leads to profound T cell-mediated immunosuppression. This study reports
      the biological effects and mechanism of action of Imm-H on malignant T cell lines
      and on normal activated human peripheral T cells. Imm-H inhibits the growth of
      malignant T cell leukemia lines with the induction of apoptosis. Imm-H also
      inhibits activated normal human T cells after antigenic stimulation in vitro.
      However, Imm-H did not inhibit malignant B cells, colon cancer cell lines, or
      normal human nonstimulated T cells, demonstrating the selective activity of Imm
      H. The effects on leukemia cells were mediated by the cellular phosphorylation of
      deoxyguanosine and the accumulation of dGTP, an inhibitor of ribonucleotide
      diphosphate reductase. Cells were protected from the toxic effects of Imm-H when
      deoxyguanosine was absent or when deoxycytidine was present. Guanosine
      incorporation into nucleic acids was selectively blocked by Imm-H with no effect
      on guanine, adenine, adenosine, or deoxycytidine incorporation. Imm-H may have
      clinical potential for treatment of human T cell leukemia and lymphoma and for
      other diseases characterized by abnormal activation of T lymphocytes. The design
      of Imm-H from an enzymatic transition-state analysis exemplifies a powerful
      approach for developing high-affinity enzyme inhibitors with pharmacologic
      activity.

PMID- 11287639
TI  - Three-dimensional image reconstruction of dephosphorylated smooth muscle heavy
      meromyosin reveals asymmetry in the interaction between myosin heads and
      placement of subfragment 2.
AB  - Regulation of the actin-activated ATPase of smooth muscle myosin II is known to
      involve an interaction between the two heads that is controlled by
      phosphorylation of the regulatory light chain. However, the three-dimensional
      structure of this inactivated form has been unknown. We have used a lipid
      monolayer to obtain two-dimensional crystalline arrays of the unphosphorylated
      inactive form of smooth muscle heavy meromyosin suitable for structural studies
      by electron cryomicroscopy of unstained, frozen-hydrated specimens. The three
      dimensional structure reveals an asymmetric interaction between the two myosin
      heads. The ATPase activity of one head is sterically "blocked" because part of
      its actin-binding interface is positioned onto the converter domain of the second
      head. ATPase activity of the second head, which can bind actin, appears to be
      inhibited through stabilization of converter domain movements needed to release
      phosphate and achieve strong actin binding. When the subfragment 2 domain of
      heavy meromyosin is oriented as it would be in an actomyosin filament lattice,
      the position of the heads is very different from that needed to bind actin,
      suggesting an additional contribution to ATPase inhibition in situ.

PMID- 11287640
TI  - IL-1-induced NFkappa B and c-Jun N-terminal kinase (JNK) activation diverge at IL
      1 receptor-associated kinase (IRAK).
AB  - Mutant I1A cells, lacking IL-1 receptor-associated kinase (IRAK) mRNA and
      protein, have been used to study the involvement of IRAK in NFkappaB and c-Jun N
      terminal kinase (JNK) activation. A series of IRAK deletion constructs were
      expressed in I1A cells, which were then tested for their ability to respond to IL
      1. Both the N-terminal death domain and the C-terminal region of IRAK are
      required for IL-1-induced NFkappaB and JNK activation, whereas the N-proximal
      undetermined domain is required for the activation of NFkappaB but not JNK. The
      phosphorylation and ubiquitination of IRAK deletion mutants correlate tightly
      with their ability to activate NFkappaB in response to IL-1, but IRAK can mediate
      IL-1-induced JNK activation without being phosphorylated. These studies reveal
      that the IL-1-induced signaling pathways leading to NFkappaB and JNK activation
      diverge either at IRAK or at a point nearer to the receptor.

PMID- 11287641
TI  - ANX7, a candidate tumor suppressor gene for prostate cancer.
AB  - The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to
      harbor a tumor suppressor gene(s) (TSG) associated with prostate and other
      cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7
      dependent suppression of human tumor cell growth, stage-specific ANX7 expression
      in 301 prostate specimens on a prostate tissue microarray, and loss of
      heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we
      report that human tumor cell proliferation and colony formation are markedly
      reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell
      lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in
      human prostate tumor microarrays reveals a significantly higher rate of loss of
      ANX7 expression in metastatic and local recurrences of hormone refractory
      prostate cancer as compared with primary tumors (P = 0.0001). Using four
      microsatellite markers at or near the ANX7 locus, and laser capture
      microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The
      microsatellite marker closest to the ANX7 locus showed the highest rate of LOH,
      including one homozygous deletion. We conclude that the ANX7 gene exhibits many
      biological and genetic properties expected of a TSG and may play a role in
      prostate cancer progression.

PMID- 11287642
TI  - Selective ablation of retinoid X receptor alpha in hepatocytes impairs their
      lifespan and regenerative capacity.
AB  - Retinoid X receptors (RXRs) are involved in a number of signaling pathways as
      heterodimeric partners of numerous nuclear receptors. Hepatocytes express high
      levels of the RXRalpha isotype, as well as several of its putative heterodimeric
      partners. Germ-line disruption (knockout) of RXRalpha has been shown to be lethal
      in utero, thus precluding analysis of its function at later life stages.
      Hepatocyte-specific disruption of RXRalpha during liver organogenesis has
      recently revealed that the presence of hepatocytes is not mandatory for the
      mouse, at least under normal mouse facility conditions, even though a number of
      metabolic events are impaired [Wan, Y.-J., et al. (2000) Mol. Cell. Biol. 20,
      4436-4444]. However, it is unknown whether RXRalpha plays a role in the control
      of hepatocyte proliferation and lifespan. Here, we report a detailed analysis of
      the liver of mice in which RXRalpha was selectively ablated in adult hepatocytes
      by using the tamoxifen-inducible chimeric Cre recombinase system. Our results
      show that the lifespan of adult hepatocytes lacking RXRalpha is shorter than that
      of their wild-type counterparts, whereas proliferative hepatocytes of
      regenerating liver exhibit an even shorter lifespan. These lifespan shortenings
      are accompanied by increased polyploidy and multinuclearity. We conclude that
      RXRalpha plays important cell-autonomous function(s) in the mechanism(s) involved
      in the lifespan of hepatocytes and liver regeneration.

PMID- 11287643
TI  - On the absorbance changes in the photocycle of the photoactive yellow protein: a
      quantum-chemical analysis.
AB  - Spectral changes in the photocycle of the photoactive yellow protein (PYP) are
      investigated by using ab initio multiconfigurational second-order perturbation
      theory at the available structures experimentally determined. Using the dark
      ground-state crystal structure [Genick, U. K., Soltis, S. M., Kuhn, P.,
      Canestrelli, I. L. & Getzoff, E. D. (1998) Nature (London) 392, 206-209], the
      pipi* transition to the lowest excited state is related to the typical blue-light
      absorption observed at 446 nm. The different nature of the second excited state
      (npi*) is consistent with the alternative route detected at 395-nm excitation.
      The results suggest the low-temperature photoproduct PYP(HL) as the most
      plausible candidate for the assignment of the cryogenically trapped early
      intermediate (Genick et al.). We cannot establish, however, a successful
      correspondence between the theoretical spectrum for the nanosecond time-resolved
      x-ray structure [Perman, B., Srajer, V., Ren, Z., Teng, T., Pradervand, C., et
      al. (1998) Science 279, 1946-1950] and any of the spectroscopic photoproducts
      known up to date. It is fully confirmed that the colorless light-activated
      intermediate recorded by millisecond time-resolved crystallography [Genick, U.
      K., Borgstahl, G. E. O., Ng, K., Ren, Z., Pradervand, C., et al. (1997) Science
      275, 1471-1475] is protonated, nicely matching the spectroscopic features of the
      photoproduct PYP(M). The overall contribution demonstrates that a combined
      analysis of high-level theoretical results and experimental data can be of great
      value to perform assignments of detected intermediates in a photocycle.

PMID- 11287644
TI  - Localization of CD4+ T cell epitope hotspots to exposed strands of HIV envelope
      glycoprotein suggests structural influences on antigen processing.
AB  - The spectrum of immunogenic epitopes presented by the H2-IA(b) MHC class II
      molecule to CD4(+) T cells has been defined for two different (clade B and clade
      D) HIV envelope (gp140) glycoproteins. Hybridoma T cell lines were generated from
      mice immunized by a sequential prime and boost regime with DNA, recombinant
      vaccinia viruses, and protein. The epitopes recognized by reactive T cell
      hybridomas then were characterized with overlapping peptides synthesized to span
      the entire gp140 sequence. Evidence of clonality also was assessed with
      antibodies to T cell receptor Valpha and Vbeta chains. A total of 80 unique
      clonotypes were characterized from six individual mice. Immunogenic peptides were
      identified within only four regions of the HIV envelope. These epitope hotspots
      comprised relatively short sequences ( approximately 20-80 aa in length) that
      were generally bordered by regions of heavy glycosylation. Analysis in the
      context of the gp120 crystal structure showed a pattern of uniform distribution
      to exposed, nonhelical strands of the protein. A likely explanation is that the
      physical location of the peptide within the native protein leads to differential
      antigen processing and consequent epitope selection.

PMID- 11287645
TI  - Polymerization of a single protein of the pathogen Yersinia enterocolitica into
      needles punctures eukaryotic cells.
AB  - A number of pathogenic, Gram-negative bacteria are able to secrete specific
      proteins across three membranes: the inner and outer bacterial membrane and the
      eukaryotic plasma membrane. In the pathogen Yersinia enterocolitica, the primary
      structure of the secreted proteins as well as of the components of the secretion
      machinery, both plasmid-encoded, is known. However, the mechanism of protein
      translocation is largely unknown. Here we show that Y. enterocolitica polymerizes
      a 6-kDa protein of the secretion machinery into needles that are able to puncture
      the eukaryotic plasma membrane. These needles form a conduit for the transport of
      specific proteins from the bacterial to the eukaryotic cytoplasm, where they
      exert their cytotoxic activity. In negatively stained electron micrographs, the
      isolated needles were 60-80 nm long and 6-7 nm wide and contained a hollow center
      of about 2 nm. Our data indicate that it is the polymerization of the 6-kDa
      protein into these needles that provides the force to perforate the eukaryotic
      plasma membrane.

PMID- 11287646
TI  - Rethinking the role of phosducin: light-regulated binding of phosducin to 14-3-3
      in rod inner segments.
AB  - Phosducin (Pd), a small protein found abundantly in photoreceptors, is widely
      assumed to regulate light sensitivity in the rod outer segment through
      interaction with the heterotrimeric G protein transducin. But, based on
      histochemistry and Western blot analysis, Pd is found almost entirely in the
      inner segment in both light and dark, most abundantly near the rod synapse. We
      report a second small protein, 14-3-3, in the rod with a similar distribution. By
      immunoprecipitation, phospho-Pd is found to interact with 14-3-3 in material from
      dark-adapted retina, and this interaction is markedly diminished by light, which
      dephosphorylates Pd. Conversely, unphosphorylated Pd binds to inner segment G
      protein(s) in the light. From these results and reported functions of 14-3-3, we
      have constructed a hypothesis for the regulation of light sensitivity at the
      level of rod synapse. By dissociating the Pd/14-3-3 complex, light enables both
      proteins to function in this role.

PMID- 11287647
TI  - Prion protein: evolution caught en route.
AB  - The prion protein displays a unique structural ambiguity in that it can adopt
      multiple stable conformations under physiological conditions. In our view, this
      puzzling feature resulted from a sudden environmental change in evolution when
      the prion, previously an integral membrane protein, got expelled into the
      extracellular space. Analysis of known vertebrate prions unveils a primordial
      transmembrane protein encrypted in their sequence, underlying this relocalization
      hypothesis. Apparently, the time elapsed since this event was insufficient to
      create a "minimally frustrated" sequence in the new milieu, probably due to the
      functional constraints set by the importance of the very flexibility that was
      created in the relocalization. This scenario may explain why, in a structural
      sense, the prion protein is still en route toward becoming a foldable globular
      protein.

PMID- 11287648
TI  - Biogeographic range expansion into South America by Coccidioides immitis mirrors
      New World patterns of human migration.
AB  - Long-distance population dispersal leaves its characteristic signature in
      genomes, namely, reduced diversity and increased linkage between genetic markers.
      This signature enables historical patterns of range expansion to be traced.
      Herein, we use microsatellite loci from the human pathogen Coccidioides immitis
      to show that genetic diversity in this fungus is geographically partitioned
      throughout North America. In contrast, analyses of South American C. immitis show
      that this population is genetically depauperate and was founded from a single
      North American population centered in Texas. Variances of allele distributions
      show that South American C. immitis have undergone rapid population growth,
      consistent with an epidemic increase in postcolonization population size. Herein,
      we estimate the introduction into South America to have occurred within the last
      9,000-140,000 years. This range increase parallels that of Homo sapiens. Because
      of known associations between Amerindians and this fungus, we suggest that the
      colonization of South America by C. immitis represents a relatively recent and
      rapid codispersal of a host and its pathogen.

PMID- 11287649
TI  - Expression of the telomerase catalytic subunit, hTERT, induces resistance to
      transforming growth factor beta growth inhibition in p16INK4A(-) human mammary
      epithelial cells.
AB  - Failures to arrest growth in response to senescence or transforming growth factor
      beta (TGF-beta) are key derangements associated with carcinoma progression. We
      report that activation of telomerase activity may overcome both inhibitory
      pathways. Ectopic expression of the human telomerase catalytic subunit, hTERT, in
      cultured human mammary epithelial cells (HMEC) lacking both telomerase activity
      and p16(INK4A) resulted in gaining the ability to maintain indefinite growth in
      the absence and presence of TGF-beta. The ability to maintain growth in TGF-beta
      was independent of telomere length and required catalytically active telomerase
      capable of telomere maintenance in vivo. The capacity of ectopic hTERT to induce
      TGF-beta resistance may explain our previously described gain of TGF-beta
      resistance after reactivation of endogenous telomerase activity in rare
      carcinogen-treated HMEC. In those HMEC that overcame senescence, both telomerase
      activity and TGF-beta resistance were acquired gradually during a process we have
      termed conversion. This effect of hTERT may model a key change occurring during
      in vivo human breast carcinogenesis.

PMID- 11287651
TI  - Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate
      synthase.
AB  - Undecaprenyl diphosphate synthase (UPS) catalyzes the cis-prenyl chain elongation
      onto trans, trans-farnesyl diphosphate (FPP) to produce undecaprenyl diphosphate
      (UPP), which is indispensable for the biosynthesis of bacterial cell walls. We
      report here the crystal structure of UPS as the only three-dimensional structure
      among cis-prenyl chain elongating enzymes. The structure is classified into a
      protein fold family and is completely different from the so-called "isoprenoid
      synthase fold" that is believed to be a common structure for the enzymes relating
      to isoprenoid biosynthesis. Conserved amino acid residues among cis-prenyl chain
      elongating enzymes are located around a large hydrophobic cleft in the UPS
      structure. A structural P-loop motif, which frequently appears in the various
      kinds of phosphate binding site, is found at the entrance of this cleft. The
      catalytic site is determined on the basis of these structural features, from
      which a possible reaction mechanism is proposed.

PMID- 11287650
TI  - Noninvasive functional optical spectroscopy of human breast tissue.
AB  - Near infrared diffuse optical spectroscopy and diffuse optical imaging are
      promising methods that eventually may enhance or replace existing technologies
      for breast cancer screening and diagnosis. These techniques are based on highly
      sensitive, quantitative measurements of optical and functional contrast between
      healthy and diseased tissue. In this study, we examine whether changes in breast
      physiology caused by exogenous hormones, aging, and fluctuations during the
      menstrual cycle result in significant alterations in breast tissue optical
      contrast. A noninvasive quantitative diffuse optical spectroscopy technique,
      frequency-domain photon migration, was used. Measurements were performed on 14
      volunteer subjects by using a hand-held probe. Intrinsic tissue absorption and
      reduced scattering parameters were calculated from frequency-domain photon
      migration data. Wavelength-dependent absorption (at 674, 803, 849, and 956 nm)
      was used to determine tissue concentration of oxyhemoglobin, deoxyhemoglobin,
      total hemoglobin, tissue hemoglobin oxygen saturation, and bulk water content.
      Results show significant and dramatic differences in optical properties between
      menopausal states. Average premenopausal intrinsic tissue absorption and reduced
      scattering values at each wavelength are 2.5- to 3-fold higher and 16-28 %
      greater, respectively, than absorption and scattering for postmenopausal
      subjects. Absorption and scattering properties for women using hormone
      replacement therapy are intermediate between premenopausal and postmenopausal
      populations. Physiological properties show differences in mean total hemoglobin
      (7.0 microM, 11.8 microM, and 19.2 microM) and water concentration relative to
      pure water (10.9 %, 15.3 %, and 27.3 %) for postmenopausal, hormone replacement
      therapy, and premenopausal subjects, respectively. Because of their unique,
      quantitative information content, diffuse optical methods may play an important
      role in breast diagnostics and improving our understanding of breast disease.

PMID- 11287652
TI  - Proteomic analysis of the bacterial cell cycle.
AB  - A global approach was used to analyze protein synthesis and stability during the
      cell cycle of the bacterium Caulobacter crescentus. Approximately one-fourth
      (979) of the estimated C. crescentus gene products were detected by two
      dimensional gel electrophoresis, 144 of which showed differential cell cycle
      expression patterns. Eighty-one of these proteins were identified by mass
      spectrometry and were assigned to a wide variety of functional groups. Pattern
      analysis revealed that coexpression groups were functionally clustered. A total
      of 48 proteins were rapidly degraded in the course of one cell cycle. More than
      half of these unstable proteins were also found to be synthesized in a cell cycle
      dependent manner, establishing a strong correlation between rapid protein
      turnover and the periodicity of the bacterial cell cycle. This is, to our
      knowledge, the first evidence for a global role of proteolysis in bacterial cell
      cycle control.

PMID- 11287653
TI  - Chrysanthemyl diphosphate synthase: isolation of the gene and characterization of
      the recombinant non-head-to-tail monoterpene synthase from Chrysanthemum
      cinerariaefolium.
AB  - Chrysanthemyl diphosphate synthase (CPPase) catalyzes the condensation of two
      molecules of dimethylallyl diphosphate to produce chrysanthemyl diphosphate
      (CPP), a monoterpene with a non-head-to-tail or irregular c1'-2-3 linkage between
      isoprenoid units. Irregular monoterpenes are common in Chrysanthemum
      cinerariaefolium and related members of the Asteraceae family. In C.
      cinerariaefolium, CPP is an intermediate in the biosynthesis of the pyrethrin
      ester insecticides. CPPase was purified from immature chrysanthemum flowers, and
      the N terminus of the protein was sequenced. A C. cinerariaefolium lambda cDNA
      library was screened by using degenerate oligonucleotide probes based on the
      amino acid sequence to identify a CPPase clone that encoded a 45-kDa preprotein.
      The first 50 aa of the ORF constitute a putative plastidial targeting sequence.
      Recombinant CPPase bearing an N-terminal polyhistidine affinity tag in place of
      the targeting sequence was purified to homogeneity from an overproducing
      Escherichia coli strain by Ni(2+) chromatography. Incubation of recombinant
      CPPase with dimethylallyl diphosphate produced CPP. The diphosphate ester was
      hydrolyzed by alkaline phosphatase, and the resulting monoterpene alcohol was
      analyzed by GC/MS to confirm its structure. The amino acid sequence of CPPase
      aligns closely with that of the chain elongation prenyltransferase farnesyl
      diphosphate synthase rather than squalene synthase or phytoene synthase, which
      catalyze c1'-2-3 cyclopropanation reactions similar to the CPPase reaction.

PMID- 11287654
TI  - X-ray structure of the human hyperplastic discs protein: an ortholog of the C
      terminal domain of poly(A)-binding protein.
AB  - The poly(A)-binding protein (PABP) recognizes the 3' mRNA poly(A) tail and plays
      an essential role in eukaryotic translation initiation and mRNA
      stabilization/degradation. PABP is a modular protein, with four N-terminal RNA
      binding domains and an extensive C terminus. The C-terminal region of PABP is
      essential for normal growth in yeast and has been implicated in mediating PABP
      homo-oligomerization and protein-protein interactions. A small, proteolytically
      stable, highly conserved domain has been identified within this C-terminal
      segment. Remarkably, this domain is also present in the hyperplastic discs
      protein (HYD) family of ubiquitin ligases. To better understand the function of
      this conserved region, an x-ray structure of the PABP-like segment of the human
      HYD protein has been determined at 1.04-A resolution. The conserved domain adopts
      a novel fold resembling a right-handed supercoil of four alpha-helices. Sequence
      profile searches and comparative protein structure modeling identified a small
      ORF from the Arabidopsis thaliana genome that encodes a structurally similar but
      distantly related PABP/HYD domain. Phylogenetic analysis of the experimentally
      determined (HYD) and homology modeled (PABP) protein surfaces revealed a
      conserved feature that may be responsible for binding to a PABP interacting
      protein, Paip1, and other shared interaction partners.

PMID- 11287655
TI  - Mechanisms of migraine aura revealed by functional MRI in human visual cortex.
AB  - Cortical spreading depression (CSD) has been suggested to underlie migraine
      visual aura. However, it has been challenging to test this hypothesis in human
      cerebral cortex. Using high-field functional MRI with near-continuous recording
      during visual aura in three subjects, we observed blood oxygenation level
      dependent (BOLD) signal changes that demonstrated at least eight characteristics
      of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in
      BOLD signal (possibly reflecting vasodilation), developed within extrastriate
      cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 +/-
      1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual
      percept. Following the same retinotopic progression, the BOLD signal then
      diminished (possibly reflecting vasoconstriction after the initial vasodilation),
      as did the BOLD response to visual activation. During periods with no visual
      stimulation, but while the subject was experiencing scintillations, BOLD signal
      followed the retinotopic progression of the visual percept. These data strongly
      suggest that an electrophysiological event such as CSD generates the aura in
      human visual cortex.

PMID- 11287656
TI  - F-spondin is a contact-repellent molecule for embryonic motor neurons.
AB  - The floor plate plays a key role in patterning axonal trajectory in the embryonic
      spinal cord by providing both long-range and local guidance cues that promote or
      inhibit axonal growth toward and across the ventral midline of the spinal cord,
      thus acting as an intermediate target for a number of crossing (commissural) and
      noncrossing (motor) axons. F-spondin, a secreted adhesion molecule expressed in
      the embryonic floor plate and the caudal somite of birds, plays a dual role in
      patterning the nervous system. It promotes adhesion and outgrowth of commissural
      axons and inhibits adhesion of neural crest cells. In the current study, we
      demonstrate that outgrowth of embryonic motor axons also is inhibited by F
      spondin protein in a contact-repulsion fashion. Three independent lines of
      evidence support our hypothesis: substrate-attached F-spondin inhibits outgrowth
      of dissociated motor neurons in an outgrowth assay; F-spondin elicits acute
      growth cone collapse when applied to cultured motor neurons; and challenging
      ventral spinal cord explants with aggregates of HEK 293 cells expressing F
      spondin, causes contact-repulsion of motor neurites. Structural-functional
      studies demonstrate that the processed carboxyl-half protein that contains the
      thrombospondin type 1 repeats is more prominent in inhibiting outgrowth,
      suggesting that the processing of F-spondin is important for enhancing its
      inhibitory activity.

PMID- 11287657
TI  - Maximum likelihood estimation of a migration matrix and effective population
      sizes in n subpopulations by using a coalescent approach.
AB  - A maximum likelihood estimator based on the coalescent for unequal migration
      rates and different subpopulation sizes is developed. The method uses a Markov
      chain Monte Carlo approach to investigate possible genealogies with branch
      lengths and with migration events. Properties of the new method are shown by
      using simulated data from a four-population n-island model and a source-sink
      population model. Our estimation method as coded in migrate is tested against
      genetree; both programs deliver a very similar likelihood surface. The algorithm
      converges to the estimates fairly quickly, even when the Markov chain is started
      from unfavorable parameters. The method was used to estimate gene flow in the
      Nile valley by using mtDNA data from three human populations.

PMID- 11287658
TI  - Extracellular matrix composition determines the transcriptional response to
      epidermal growth factor receptor activation.
AB  - The transcriptional response to epidermal growth factor (EGF) was examined in a
      cultured cell model of adhesion. Gene expression was monitored in human embryonic
      kidney cells (HEK293) after attachment of cells to the extracellular matrix (ECM)
      proteins, laminin, and fibronectin, by using complementary DNA microarrays
      printed with 1,718 individual human genes. Cluster analysis revealed that the
      influence of EGF on gene expression, either positive or negative, was largely
      independent of ECM composition. However, clusters of EGF-regulated genes were
      identified that were diagnostic of the type of ECM proteins to which cells were
      attached. In these clusters, attachment of cells to a laminin or fibronectin
      substrata specifically modified the direction of gene expression changes in
      response to EGF stimulation. For example, in HEK293 cells attached to
      fibronectin, EGF stimulated an increase in the expression of some genes; however,
      genes in the same group were nonresponsive or even suppressed in cells attached
      to laminin. Many of the genes regulated by EGF and ECM proteins in this manner
      are involved in ECM and cytoskeletal architecture, protein synthesis, and cell
      cycle control, indicating that cell responses to EGF stimulation can be
      dramatically affected by ECM composition.

PMID- 11287659
TI  - Allostatic load as a marker of cumulative biological risk: MacArthur studies of
      successful aging.
AB  - Allostatic load (AL) has been proposed as a new conceptualization of cumulative
      biological burden exacted on the body through attempts to adapt to life's
      demands. Using a multisystem summary measure of AL, we evaluated its capacity to
      predict four categories of health outcomes, 7 years after a baseline survey of
      1,189 men and women age 70-79. Higher baseline AL scores were associated with
      significantly increased risk for 7-year mortality as well as declines in
      cognitive and physical functioning and were marginally associated with incident
      cardiovascular disease events, independent of standard socio-demographic
      characteristics and baseline health status. The summary AL measure was based on
      10 parameters of biological functioning, four of which are primary mediators in
      the cascade from perceived challenges to downstream health outcomes. Six of the
      components are secondary mediators reflecting primarily components of the
      metabolic syndrome (syndrome X). AL was a better predictor of mortality and
      decline in physical functioning than either the syndrome X or primary mediator
      components alone. The findings support the concept of AL as a measure of
      cumulative biological burden.

PMID- 11287660
TI  - Differentiation of embryonic mesenchymal cells to odontoblast-like cells by
      overexpression of dentin matrix protein 1.
AB  - Cells of the craniofacial skeleton are derived from a common mesenchymal
      progenitor. The regulatory factors that control their differentiation into
      various cell lineages are unknown. To investigate the biological function of
      dentin matrix protein 1 (DMP1), an extracellular matrix gene involved in
      calcified tissue formation, stable transgenic cell lines and adenovirally
      infected cells overexpressing DMP1 were generated. The findings in this paper
      demonstrate that overexpression of DMP1 in pluripotent and mesenchyme-derived
      cells such as C3H10T1/2, MC3T3-E1, and RPC-C2A can induce these cells to
      differentiate and form functional odontoblast-like cells. Functional
      differentiation of odontoblasts requires unique sets of genes being turned on and
      off in a growth- and differentiation-specific manner. The genes studied include
      transcription factors like core binding factor 1 (Cbfa1), bone morphogenetic
      protein 2 (BMP2), and BMP4; early markers for extracellular matrix deposition
      like alkaline phosphatase (ALP), osteopontin, osteonectin, and osteocalcin; and
      late markers like DMP2 and dentin sialoprotein (DSP) that are expressed by
      terminally differentiated odontoblasts and are responsible for the formation of
      tissue-specific dentin matrix. However, this differentiation pathway was limited
      to mesenchyme-derived cells only. Other cell lines tested by the adenoviral
      expression system failed to express odontoblast-phenotypic specific genes. An in
      vitro mineralized nodule formation assay demonstrated that overexpressed cells
      could differentiate and form a mineralized matrix. Furthermore, we also
      demonstrate that phosphorylation of Cbfa1 (osteoblast-specific transcription
      factor) was not required for the expression of odontoblast-specific genes,
      indicating the involvement of other unidentified odontoblast-specific
      transcription factors or coactivators. Cell lines that differentiate into
      odontoblast-like cells are useful tools for studying the mechanism involved in
      the terminal differentiation process of these postmitotic cells.

PMID- 11287661
TI  - An important function of Nrf2 in combating oxidative stress: detoxification of
      acetaminophen.
AB  - Nrf2, a member of the "cap 'n collar" group of transcription factors, is
      important for protecting cells against oxidative damage. We investigated its role
      in the detoxification of acetaminophen [N-acetyl-p-aminophenol (APAP)]-induced
      hepatotoxicity. When Nrf2 knockout (Nrf2(-/-)) and wild-type mice were given APAP
      by i.p. injection, the Nrf2(-/-) mice were highly susceptible to APAP treatment.
      With doses of APAP that were tolerated by wild-type mice, the Nrf2(-/-) mice died
      of liver failure. When hepatic glutathione was depleted after a dose of 400 mg/kg
      of APAP, the wild-type mice were able to compensate and regain the normal
      glutathione level. In contrast, the glutathione level in the Nrf2(-/-) mice was
      not compensated and remained low. This was because of the decrease in the gene
      expression of gcs(H) and gcs(L) as well as gss in the livers of the Nrf2(-/-)
      mice. In addition, the expression of ugt1a6 and gstpi that detoxify APAP by
      conjugation was also decreased. This increased susceptibility of the Nrf2(-/-)
      mice to APAP, because of an impaired capacity to replenish their glutathione
      stores, compounded with a decreased detoxification capability, highlights the
      importance of Nrf2 in the regulation of glutathione synthesis and cellular
      detoxification processes.

PMID- 11287663
TI  - On a psychophysical transformed-rule up and down method converging on a 75% level
      of correct responses.
AB  - Transformed-rule up and down psychophysical methods have gained great popularity,
      mainly because they combine criterion-free responses with an adaptive procedure
      allowing rapid determination of an average stimulus threshold at various
      criterion levels of correct responses. The statistical theory underlying the
      methods now in routine use is based on sets of consecutive responses with assumed
      constant probabilities of occurrence. The response rules requiring consecutive
      responses prevent the possibility of using the most desirable response criterion,
      that of 75% correct responses. The earliest transformed-rule up and down method,
      whose rules included nonconsecutive responses, did not contain this limitation
      but failed to become generally accepted, lacking a published theoretical
      foundation. Such a foundation is provided in this article and is validated
      empirically with the help of experiments on human subjects and a computer
      simulation. In addition to allowing the criterion of 75% correct responses, the
      method is more efficient than the methods excluding nonconsecutive responses in
      their rules.

PMID- 11287664
TI  - Can medial temporal lobe regions distinguish true from false? An event-related
      functional MRI study of veridical and illusory recognition memory.
AB  - To investigate the types of memory traces recovered by the medial temporal lobe
      (MTL), neural activity during veridical and illusory recognition was measured
      with the use of functional MRI (fMRI). Twelve healthy young adults watched a
      videotape segment in which two speakers alternatively presented lists of
      associated words, and then the subjects performed a recognition test including
      words presented in the study lists (True items), new words closely related to
      studied words (False items), and new unrelated words (New items). The main
      finding was a dissociation between two MTL regions: whereas the hippocampus was
      similarly activated for True and False items, suggesting the recovery of semantic
      information, the parahippocampal gyrus was more activated for True than for False
      items, suggesting the recovery of perceptual information. The study also yielded
      a dissociation between two prefrontal cortex (PFC) regions: whereas bilateral
      dorsolateral PFC was more activated for True and False items than for New items,
      possibly reflecting monitoring of retrieved information, left ventrolateral PFC
      was more activated for New than for True and False items, possibly reflecting
      semantic processing. Precuneus and lateral parietal regions were more activated
      for True and False than for New items. Orbitofrontal cortex and cerebellar
      regions were more activated for False than for True items. In conclusion, the
      results suggest that activity in anterior MTL regions does not distinguish True
      from False, whereas activity in posterior MTL regions does.

PMID- 11287665
TI  - Diacylglycerol kinase epsilon regulates seizure susceptibility and long-term
      potentiation through arachidonoyl- inositol lipid signaling.
AB  - Arachidonoyldiacylglycerol (20:4-DAG) is a second messenger derived from
      phosphatidylinositol 4,5-bisphosphate and generated by stimulation of glutamate
      metabotropic receptors linked to G proteins and activation of phospholipase C.
      20:4-DAG signaling is terminated by its phosphorylation to phosphatidic acid,
      catalyzed by diacylglycerol kinase (DGK). We have cloned the murine DGKepsilon
      gene that showed, when expressed in COS-7 cells, selectivity for 20:4-DAG. The
      significance of DGKepsilon in synaptic function was investigated in mice with
      targeted disruption of the DGKepsilon. DGKepsilon(-/-) mice showed a higher
      resistance to electroconvulsive shock with shorter tonic seizures and faster
      recovery than DGKepsilon(+/+) mice. The phosphatidylinositol 4,5-bisphosphate
      signaling pathway in cerebral cortex was greatly affected, leading to lower
      accumulation of 20:4-DAG and free 20:4. Also, long-term potentiation was
      attenuated in perforant path-dentate granular cell synapses. We propose that
      DGKepsilon contributes to modulate neuronal signaling pathways linked to synaptic
      activity, neuronal plasticity, and epileptogenesis.

PMID- 11287666
TI  - Translocation pathway of protein substrates in ClpAP protease.
AB  - Intracellular protein degradation, which must be tightly controlled to protect
      normal proteins, is carried out by ATP-dependent proteases. These multicomponent
      enzymes have chaperone-like ATPases that recognize and unfold protein substrates
      and deliver them to the proteinase components for digestion. In ClpAP, hexameric
      rings of the ClpA ATPase stack axially on either face of the ClpP proteinase,
      which consists of two apposed heptameric rings. We have used cryoelectron
      microscopy to characterize interactions of ClpAP with the model substrate,
      bacteriophage P1 protein, RepA. In complexes stabilized by ATPgammaS, which bind
      but do not process substrate, RepA dimers are seen at near-axial sites on the
      distal surface of ClpA. On ATP addition, RepA is translocated through
      approximately 150 A into the digestion chamber inside ClpP. Little change is
      observed in ClpAP, implying that translocation proceeds without major
      reorganization of the ClpA hexamer. When translocation is observed in complexes
      containing a ClpP mutant whose digestion chamber is already occupied by
      unprocessed propeptides, a small increase in density is observed within ClpP, and
      RepA-associated density is also seen at other axial sites. These sites appear to
      represent intermediate points on the translocation pathway, at which segments of
      unfolded RepA subunits transiently accumulate en route to the digestion chamber.

PMID- 11287667
TI  - Jasmonic acid carboxyl methyltransferase: a key enzyme for jasmonate-regulated
      plant responses.
AB  - Methyl jasmonate is a plant volatile that acts as an important cellular regulator
      mediating diverse developmental processes and defense responses. We have cloned
      the novel gene JMT encoding an S-adenosyl-l-methionine:jasmonic acid carboxyl
      methyltransferase (JMT) from Arabidopsis thaliana. Recombinant JMT protein
      expressed in Escherichia coli catalyzed the formation of methyl jasmonate from
      jasmonic acid with K(m) value of 38.5 microM. JMT RNA was not detected in young
      seedlings but was detected in rosettes, cauline leaves, and developing flowers.
      In addition, expression of the gene was induced both locally and systemically by
      wounding or methyl jasmonate treatment. This result suggests that JMT can
      perceive and respond to local and systemic signals generated by external stimuli,
      and that the signals may include methyl jasmonate itself. Transgenic Arabidopsis
      overexpressing JMT had a 3-fold elevated level of endogenous methyl jasmonate
      without altering jasmonic acid content. The transgenic plants exhibited
      constitutive expression of jasmonate-responsive genes, including VSP and PDF1.2.
      Furthermore, the transgenic plants showed enhanced level of resistance against
      the virulent fungus Botrytis cinerea. Thus, our data suggest that the jasmonic
      acid carboxyl methyltransferase is a key enzyme for jasmonate-regulated plant
      responses. Activation of JMT expression leads to production of methyl jasmonate
      that could act as an intracellular regulator, a diffusible intercellular signal
      transducer, and an airborne signal mediating intra- and interplant
      communications.

PMID- 11287668
TI  - HDA2 and HDA3 are related proteins that interact with and are essential for the
      activity of the yeast histone deacetylase HDA1.
AB  - Histone deacetylase HDA1, the prototype for the class II mammalian deacetylases,
      is likely the catalytic subunit of the HDA1-containing complex that is involved
      in TUP1-specific repression and global deacetylation in yeast. Although the class
      I RPD3-like enzymatic complexes have been well characterized, little is known
      about the identity and interactions of the factors that associate to form the
      HDA1 complex. In this paper, we identify related HDA2 and HDA3 proteins that are
      found in the HDA1 complex and show that HDA1 interacts with itself and with the
      HDA2-HDA3 subcomplex to form a likely tetramer. These interactions are necessary
      for catalytic activity because mutations in any of the three components disrupt
      activity both in vitro and in vivo. In this respect the HDA1 complex differs from
      yeast RPD3, which has components such as SIN3 that are not essential for activity
      in vitro, and yeast HOS3, which has intrinsic in vitro activity as a homodimer in
      the absence of other subunits.

PMID- 11287669
TI  - Ccm1, a regulatory gene controlling the induction of a carbon-concentrating
      mechanism in Chlamydomonas reinhardtii by sensing CO2 availability.
AB  - Aquatic photosynthetic organisms, including the green alga Chlamydomonas
      reinhardtii, induce a set of genes for a carbon-concentrating mechanism (CCM) to
      acclimate to CO2-limiting conditions. This acclimation is modulated by some
      mechanisms in the cell to sense CO2 availability. Previously, a high-CO2
      requiring mutant C16 defective in an induction of the CCM was isolated from C.
      reinhardtii by gene tagging. By using this pleiotropic mutant, we isolated a
      nuclear regulatory gene, Ccm1, encoding a 699-aa hydrophilic protein with a
      putative zinc-finger motif in its N-terminal region and a Gln repeat
      characteristic of transcriptional activators. Introduction of Ccm1 into this
      mutant restored an active carbon transport through the CCM, development of a
      pyrenoid structure in the chloroplast, and induction of a set of CCM-related
      genes. That a 5,128-base Ccm1 transcript and also the translation product of 76
      kDa were detected in both high- and low-CO2 conditions suggests that CCM1 might
      be modified posttranslationally. These data indicate that Ccm1 is essential to
      control the induction of CCM by sensing CO2 availability in Chlamydomonas cells.
      In addition, complementation assay and identification of the mutation site of
      another pleiotropic mutant, cia5, revealed that His-54 within the putative zinc
      finger motif of the CCM1 is crucial to its regulatory function.

PMID- 11287670
TI  - A postgermination developmental arrest checkpoint is mediated by abscisic acid
      and requires the ABI5 transcription factor in Arabidopsis.
AB  - Seed dormancy is a trait of considerable adaptive significance because it
      maximizes seedling survival by preventing premature germination under unfavorable
      conditions. Understanding how seeds break dormancy and initiate growth is also of
      great agricultural and biotechnological interest. Abscisic acid (ABA) plays
      primary regulatory roles in the initiation and maintenance of seed dormancy. Here
      we report that the basic leucine zipper transcription factor ABI5 confers an
      enhanced response to exogenous ABA during germination, and seedling
      establishment, as well as subsequent vegetative growth. These responses correlate
      with total ABI5 levels. We show that ABI5 expression defines a narrow
      developmental window following germination, during which plants monitor the
      environmental osmotic status before initiating vegetative growth. ABI5 is
      necessary to maintain germinated embryos in a quiescent state thereby protecting
      plants from drought. As expected for a key player in ABA-triggered processes,
      ABI5 protein accumulation, phosphorylation, stability, and activity are highly
      regulated by ABA during germination and early seedling growth.

PMID- 11287673
TI  - Conformational change of proteins arising from normal mode calculations.
AB  - A normal mode analysis of 20 proteins in 'open' or 'closed' forms was performed
      using simple potential and protein models. The quality of the results was found
      to depend upon the form of the protein studied, normal modes obtained with the
      open form of a given protein comparing better with the conformational change than
      those obtained with the closed form. Moreover, when the motion of the protein is
      a highly collective one, then, in all cases considered, there is a single low
      frequency normal mode whose direction compares well with the conformational
      change. When it is not, in most cases there is still a single low-frequency
      normal mode giving a good description of the pattern of the atomic displacements,
      as they are observed experimentally during the conformational change. Hence a lot
      of information on the nature of the conformational change of a protein is often
      found in a single low-frequency normal mode of its open form. Since this
      information can be obtained through the normal mode analysis of a model as simple
      as that used in the present study, it is likely that the property captured by
      such an analysis is for the most part a property of the shape of the protein
      itself. One of the points that has to be clarified now is whether or not amino
      acid sequences have been selected in order to allow proteins to follow a single
      normal mode direction, as least at the very beginning of their conformational
      change.

PMID- 11287671
TI  - A ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO)-like protein from
      Chlorobium tepidum that is involved with sulfur metabolism and the response to
      oxidative stress.
AB  - A gene encoding a product with substantial similarity to ribulose-1,5
      bisphosphate carboxylase/oxygenase (RubisCO) was identified in the preliminary
      genome sequence of the green sulfur bacterium Chlorobium tepidum. A highly
      similar gene was subsequently isolated and sequenced from Chlorobium limicola
      f.sp. thiosulfatophilum strain Tassajara. Analysis of these amino acid sequences
      indicated that they lacked several conserved RubisCO active site residues. The
      Chlorobium RubisCO-like proteins are most closely related to deduced sequences in
      Bacillus subtilis and Archaeoglobus fulgidus, which also lack some typical
      RubisCO active site residues. When the C. tepidum gene encoding the RubisCO-like
      protein was disrupted, the resulting mutant strain displayed a pleiotropic
      phenotype with defects in photopigment content, photoautotrophic growth and
      carbon fixation rates, and sulfur metabolism. Most important, the mutant strain
      showed substantially enhanced accumulation of two oxidative stress proteins.
      These results indicated that the C. tepidum RubisCO-like protein might be
      involved in oxidative stress responses and/or sulfur metabolism. This protein
      might be an evolutional link to bona fide RubisCO and could serve as an important
      tool to analyze how the RubisCO active site developed.

PMID- 11287674
TI  - Assessing the role of tryptophan residues in the binding site.
AB  - Instead of looking at the interfacial area as a measure of the extent of a
      protein--protein recognition site, a new procedure has been developed to identify
      the importance of a specific residue, namely tryptophan, in the binding process.
      Trp residues which contribute more towards the free energy of binding have their
      accessible surface area reduced, on complex formation, for both the main-chain
      and side-chain atoms, whereas for the less important residues the reduction is
      restricted only to the aromatic ring of the side chain. The two categories of
      residues are also distinguished by the presence or absence of hydrogen bonds
      involving the Trp residue in the complex. A comparison of the observed change in
      the accessible surface area with the value calculated using an analytical
      expression provides another way of characterizing the Trp residues critical for
      binding and this has been used to identify such residues involved in binding non
      proteinaceous molecules in protein structures.

PMID- 11287675
TI  - Post-translational GPI lipid anchor modification of proteins in kingdoms of life:
      analysis of protein sequence data from complete genomes.
AB  - To investigate the occurrence of glycosylphosphatidylinositol (GPI) lipid anchor
      modification in various taxonomic ranges, potential substrate proteins have been
      searched for in completely sequenced genomes. We applied the big-pi predictor for
      the recognition of propeptide cleavage and anchor attachment sites with a new,
      generalized analytical form of the extreme-value distribution for evaluating
      false-positive prediction rates. (i) We find that GPI modification is present
      among lower and higher Eukaryota (approximately 0.5% of all proteins) but it
      seems absent in all eubacterial and three archaeobacterial species studied. Four
      other archaean genomes appear to encode such a fraction of substrate proteins (in
      the range of eukaryots) that they cannot be explained as false-positive
      predictions. This result supports the possible existence of GPI anchor
      modification in an archaean subgroup. (ii) The frequency of GPI-modified proteins
      on various chromosomes of a given eukaryotic species is different. (iii) Lists of
      potentially GPI-modified proteins in complete genomes with their predicted
      cleavage sites are available at
      http://mendel.imp.univie.ac.at/gpi/gpi_genomes.html. (iv) Orthologues of known
      transamidase subunits have been found only for EUKARYA: Inconsistencies in domain
      structure among homologues some of which may indicate sequencing errors are
      described. We present a refined model of the transamidase complex.

PMID- 11287676
TI  - Prediction of the structure of human Janus kinase 2 (JAK2) comprising the two
      carboxy-terminal domains reveals a mechanism for autoregulation.
AB  - The structure of human Janus kinase 2 (JAK2) comprising the two C-terminal
      domains (JH1 and JH2) was predicted by application of homology modelling
      techniques. JH1 and JH2 represent the tyrosine kinase and tyrosine kinase-like
      domains, respectively, and are crucial for function and regulation of the
      protein. A comparison between the structures of the two domains is made and
      structural differences are highlighted. Prediction of the relative orientation of
      JH1 and JH2 was aided by a newly developed method for the detection of correlated
      amino acid mutations. Analysis of the interactions between the two domains led to
      a model for the regulatory effect of JH2 on JH1. The predictions are consistent
      with available experimental data on JAK2 or related proteins and provide an
      explanation for inhibition of JH1 tyrosine kinase activity by the adjacent JH2
      domain.

PMID- 11287677
TI  - Design of inhibitors of Ras--Raf interaction using a computational combinatorial
      algorithm.
AB  - Drugs that inhibit important protein-protein interactions are hard to find either
      by screening or rational design, at least so far. Most drugs on the market that
      target proteins today are therefore aimed at well-defined binding pockets in
      proteins. While computer-aided design is widely used to facilitate the drug
      discovery process for binding pockets, its application to the design of
      inhibitors that target the protein surface initially seems to be limited because
      of the increased complexity of the task. Previously, we had started to develop a
      computational combinatorial design approach based on the well-known 'multiple
      copy simultaneous search' (MCSS) procedure to tackle this problem. In order to
      identify sequence patterns of potential inhibitor peptides, a three-step
      procedure is employed: first, using MCSS, the locations of specific functional
      groups on the protein surface are identified; second, after constructing the
      peptide main chain based on the location of favorite locations of N
      methylacetamide groups, functional groups corresponding to amino acid side chains
      are selected and connected to the main chain C(alpha) atoms; finally, the
      peptides generated in the second step are aligned and probabilities of amino
      acids at each position are calculated from the alignment scheme. Sequence
      patterns of potential inhibitors are determined based on the propensities of
      amino acids at each C(alpha) position. Here we report the optimization of
      inhibitor peptides using the sequence patterns determined by our method. Several
      short peptides derived from our prediction inhibit the Ras--Raf association in
      vitro in ELISA competition assays, radioassays and biosensor-based assays,
      demonstrating the feasibility of our approach. Consequently, our method provides
      an important step towards the development of novel anti-Ras agents and the
      structure-based design of inhibitors of protein--protein interactions.

PMID- 11287678
TI  - Experimental and computational mapping of the binding surface of a crystalline
      protein.
AB  - Multiple Solvent Crystal Structures (MSCS) is a crystallographic technique to
      identify energetically favorable positions and orientations of small organic
      molecules on the surface of proteins. We determined the high-resolution crystal
      structures of thermolysin (TLN), generated from crystals soaked in 50--70%
      acetone, 50--80% acetonitrile and 50 mM phenol. The structures of the protein in
      the aqueous-organic mixtures are essentially the same as the native enzyme and a
      number of solvent interaction sites were identified. The distribution of probe
      molecules shows clusters in the main specificity pocket of the active site and a
      buried subsite. Within the active site, we compared the experimentally determined
      solvent positions with predictions from two computational functional group
      mapping techniques, GRID and Multiple Copy Simultaneous Search (MCSS). The
      experimentally determined small molecule positions are consistent with the
      structures of known protein--ligand complexes of TLN.

PMID- 11287679
TI  - Structure-function studies of an IGF-I analogue that can be chemically cleaved to
      a two-chain mini-IGF-I.
AB  - The structure and biological activities of two disulphide isomers of a C-region
      deletion mutant of insulin-like growth factor-I (IGF-I) which has an Asn--Gly
      link engineered at the junction of the A- and B-regions were studied before and
      after chemical cleavage. Circular dichroism (CD) spectra and binding affinity to
      IGF binding protein 3 (IGFBP3) indicated that the treatment with hydroxylamine
      did not disrupt the overall tertiary fold of the hormones. Cleavage restored some
      binding affinity for the IGF-I receptor in both isomers and weakly restored the
      ability to stimulate incorporation of tritiated thymidine into DNA in NIH 3T3
      fibroblasts transfected with the human IGF-I receptor. Cleavage also restored
      metabolic capacity, as measured by the ability of the isomers to promote
      lipogenesis in isolated rat adipocytes through the insulin receptor. These
      results are consistent with the theory that binding of IGF-I to the IGF-I
      receptor requires a conformational change similar to that involved in insulin
      binding the insulin receptor. The weak affinity for the IGF-I receptor after
      cleavage is consistent with the belief that residues in the C-region interact
      with the IGF-I receptor. This structural difference between insulin and IGF-I
      gives each a higher binding affinity for its own receptor.

PMID- 11287680
TI  - A central core structure in an antibody variable domain determines antigen
      specificity.
AB  - Antibody binding sites provide an adaptable surface capable of interacting with
      essentially any molecular target. Using CDR shuffling, residues important for the
      assembly of mucin-1 specific paratopes were defined by random recombination of
      the complementarity determining regions derived from a set of mucin-1 specific
      clones, previously selected from an antibody fragment library. It was found that
      positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light
      chain were conserved in many of the clones. These particular residues seem to be
      located centrally in the binding site as indicated by a structure model analysis.
      The importance of several of these conserved residues was supported by their
      presence in a mouse monoclonal antibody with a known structure and the same
      epitope specificity. Several of these corresponding residues in the mouse
      monoclonal antibody are known to interact with the antigen. In conclusion,
      critical residues important for maintaining a human antigen-specific binding site
      during the process of in vitro antibody evolution were defined. Furthermore, an
      explanation for the observed restricted germline gene usage in certain antibody
      responses against protein epitopes is provided.

PMID- 11287681
TI  - The Diploma in Genitourinary Medicine (London Society of Apothecaries).

PMID- 11287683
TI  - Measuring sexual behaviour: methodological challenges in survey research.

PMID- 11287684
TI  - Gene therapy for HIV.

PMID- 11287685
TI  - HIV associated nephropathy: a treatable condition.
AB  - OBJECTIVES: To describe current knowledge on the aetiology, pathology, diagnosis,
      and treatment of HIV associated nephropathy. METHODS: A Medline search was
      performed using the key words "HIV," "nephropathy," "renal," and "kidney." A
      further search was performed for each of the currently licensed antiretroviral
      agents linked to key words "renal" or "kidney" and also using the MeSH heading
      "pharmacokinetics." RESULTS: HIV associated nephropathy is a common complication
      of HIV in black African and Afro-Caribbean patients and presents with progressive
      renal failure and heavy proteinuria. As other causes of renal failure are likely
      to fall in incidence among patients successfully treated with highly active
      antiretroviral therapy (HAART), HIV associated nephropathy will become
      increasingly prominent as a cause of renal impairment in HIV infected patients.
      Recent evidence suggests that HIV associated nephropathy will respond to HAART
      with a dramatic improvement in renal function. CONCLUSION: HIV associated
      nephropathy is a treatable condition. This condition should be actively sought in
      HIV infected patients if they are to receive the benefits of therapy.

PMID- 11287686
TI  - No association of anti-Chlamydia trachomatis antibodies and severity of cervical
      neoplasia.
AB  - OBJECTIVE: To explore whether the presence of Chlamydia trachomatis antibodies is
      associated with the severity of neoplastic lesions in women with cervical
      dyskaryosis. METHODS: In a cross sectional study in two groups of women referred
      for an abnormal Papanicolaou smear (group A: 296, group B: 331 women) blood
      samples were analysed for antichlamydial antibodies by enzyme immunoassay.
      Cervical neoplasia was graded histologically. RESULTS: In group A no association
      was found between increasing grade of CIN and the presence of antichlamydial
      antibodies. The proportion (93%) of women with antichlamydial antibodies was
      higher in 14 women with (micro)invasive carcinoma than in women with CIN (35%).
      As the high prevalence of antichlamydial antibodies in women with cervical
      carcinoma is not consistent with prevalences reported in recent literature, we
      analysed a second group of women in which indeed the high prevalence was not
      confirmed CONCLUSION: Our results suggest that the presence of circulating
      antichlamydial antibodies is not associated with the severity of neoplastic
      lesions and it seems unlikely that C trachomatis has a role in the progression of
      cervical neoplasia.

PMID- 11287687
TI  - Endocervical Gram stain smears and their usefulness in the diagnosis of Chlamydia
      trachomatis.
AB  - OBJECTIVE: To evaluate the usefulness of endocervical Gram stain smears in the
      diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in a female
      population attending a STD clinic. METHODS: 494 females attending a STD clinic
      and undergoing a speculum examination had endocervical specimens submitted for C
      trachomatis culture, direct fluorescent antibody testing (DFA), and N gonorrhoeae
      culture. Endocervical smears were also collected for Gram stain. The number of
      polymorphonuclear leucocytes (PMN) per high power field (HPF), presence of
      bacteria, yeast, red blood cells, and clue cells were recorded. Clinical signs of
      cervicitis were also documented. RESULTS: N gonorrhoeae was isolated from one
      subject who was co-infected with C trachomatis and no further analysis was done
      regarding N gonorrhoeae. Analysis was performed on 220 participants. The
      prevalence of C trachomatis infection was 13%. Of the Gram smears collected, 55%
      were inadequate owing to the presence of vaginal contamination. There were an
      equal number of C trachomatis isolates in patients with < or = 10 PMN/HPF (48%)
      and > 10 PMN/HPF (52%). Endocervical mucopus and erythema were statistically
      significant for the presence of C trachomatis (p < 0.001 and 0.02 respectively).
      The presence of any signs of cervicitis-that is, mucopus, friability, erythema,
      and ectropion together with > 10 PMN/HPF was statistically significant for the
      presence of C trachomatis. CONCLUSION: The use of endocervical Gram smear results
      together with clinical information can be used to identify high risk women for C
      trachomatis infection.

PMID- 11287689
TI  - The prevalence of Chlamydia trachomatis infection in male undergraduates: a
      postal survey.
AB  - OBJECTIVES: To determine the prevalence of Chlamydia trachomatis infection in
      male undergraduates and to investigate whether prevalence increases with time
      spent at university. To investigate the feasibility of screening men for C
      trachomatis by self sampling and posting of urine specimens. METHODS: The study
      design was a postal survey undertaken by the Department of Genito-Urinary
      Medicine (GUM) and Student University Health Service (SUHS) in SHEFFIELD: 2607
      male undergraduates from the SUHS patient list were invited to participate in the
      study by providing a first void urine specimen and posting it to the laboratory.
      The main outcome measure was the detection of C trachomatis infection. RESULTS:
      758 students participated in the study, a response rate of 29.1%. Nine students
      (1.2%) tested positive for C trachomatis. The prevalence of infection in the
      first, second, and third year of study was 0.7%, 1.5%, and 1.6% of participants
      respectively. There was no statistically significant difference in prevalence of
      infection between first and third year students (chi(2) test, p = 0.32). However,
      students with chlamydia had a higher median age (Mann-Whitney U test, p < or =
      0.05). Contact tracing identified four further cases of C trachomatis infection.
      CONCLUSION: Screening for C trachomatis infection by postal survey is feasible.
      However, the response rate in this study was poor and the estimated sample size
      was not reached. Therefore, it has not been possible to determine the true
      prevalence of infection in this population or to accurately assess changes in
      prevalence with time spent at university.

PMID- 11287688
TI  - Cervical cytology smears in sexually transmitted infection clinics in the United
      Kingdom.
AB  - OBJECTIVES: To determine the current practice of smear taking in sexually
      transmitted infection (STI) clinics within the United Kingdom; what proportion of
      smears are taken within the national guidelines; whether clinics are screening
      women not covered by the national screening programme. To compare the abnormality
      rates of routine and opportunistic (that is, in addition to the screening
      recommendations) smears; the abnormality rates of smears taken within STI clinics
      with those taken within the community setting. METHODS: A questionnaire was
      circulated to all clinics in May 1998. Details of screening practice were
      requested. The clinics then prospectively collected details of patient's age, GP
      registration, date and result of previous smear, and current result of all smears
      taken between 11 May 1998 and 25 May 1998. RESULTS: There were 1828 smears taken
      in the 2 week period; 504 (27.6%) were opportunistic. Opportunistic smears had
      marginal significantly increased rates of low grade abnormalities but lower (but
      not statistically significant) high grade abnormalities than in routine smears.
      231 (12.6%) of the women were not registered with a GP so would not be included
      in the national programme. The national rates of abnormalities were significantly
      higher in the STI clinics compared with the community setting. CONCLUSION: The
      majority of smears taken within STI clinics fall within the national guidelines,
      and 12.6% of the women would probably not otherwise have been screened. The rates
      of abnormality were significantly higher in the STI clinics but smears taken
      opportunisticly were less likely to have high grade abnormalities. There is no
      evidence from this study to support the practice of additional smears in the
      presence of an effective national cytology screening programme.

PMID- 11287690
TI  - Sexually transmitted infections among married women in Dhaka, Bangladesh:
      unexpected high prevalence of herpes simplex type 2 infection.
AB  - OBJECTIVES: To document the prevalence of reproductive tract infections (RTI) and
      sexually transmitted infections (STI) among women attending a basic healthcare
      clinic in Dhaka, Bangladesh, to identify risk factors associated with the
      diseases and to estimate the incidence of syphilis, hepatitis C (HCV), hepatitis
      B (HBV), and herpes simplex type 2 (HSV-2) infection. METHODS: A cross sectional
      sample of 2335 consecutive women was examined during 1996-8. Women were
      interviewed about risk factors for RTI/STI and tested for Neisseria gonorrhoeae,
      Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, HIV, HCV, HBV,
      HSV-1 and HSV-2 infection as well as vaginal candidosis and bacterial vaginosis.
      Women with antibodies to T pallidum were retested at regular intervals. One year
      after ending the study seroconversion for syphilis, HBV, HCV, and HSV-2 infection
      was detected among women initially negative for the respective diseases. RESULTS:
      The overall prevalence rate of N gonorrhoeae, C trachomatis, T vaginalis, and T
      pallidum infection was 0.5%, 1.9%, 2.0%, and 2.9% respectively. Overall, 35% of
      the women had antibodies to hepatitis B core antigen, 0.9% had HCV, and 12% HSV-2
      infection. Risk factors for gonorrhoea/C trachomatis infection were a husband not
      living at home or suspected of being unfaithful. HSV-2 infection was associated
      with the same risk factors and with a polygamous marriage. The prevalence of HSV
      2 infection among women "at risk" was 23%. HIV infection was not diagnosed.
      Repeated serological examination indicated that only 32% of women with
      serological evidence of syphilis had active disease. The seroincidences of HBV,
      HCV, and HSV-2 were 0.03, 0.007, and 0.009 per person year. Seroconversion for
      syphilis was not observed.

PMID- 11287691
TI  - Prevalence and risk factors of HSV-1 and HSV-2 antibodies in European HIV
      infected women.
AB  - OBJECTIVES: To investigate the prevalence and risk factors of HSV-1 and HSV-2
      antibodies in HIV infected women and the association between recurrent genital
      ulcerations and HIV disease progression in HSV-2 positive women. METHODS: The
      presence of HSV antibodies was tested in 276 of the 487 women participating in a
      European cohort study of HIV infected women. Prevalence rate ratios described the
      association between HSV infection and its risk factors, using log binomial
      regression. Generalised estimating equations (GEE) analysis was performed to
      determine the impact of markers of HIV disease progression on recurrent genital
      ulcerations. RESULTS: The prevalence of HSV-1 and HSV-2 antibodies was 76% (95%
      confidence interval (95% CI): 71-81) and 42% (95% CI: 36-50); 30% (95% CI: 24-35)
      of the women had antibodies against both HSV-1 and HSV-2. The prevalence of HSV-1
      was 86% (95% CI: 80-92) in southern Europe compared with 69% (95% CI: 57-79) and
      67% (95% CI: 55-77) in central and northern Europe (p=0.002). This geographical
      variation remained after adjustment for other risk factors. An increasing number
      of years of sexual activity (p=0.0002) and a history of prostitution (p=0.0001)
      were independently associated with HSV-2 prevalence. In HSV-2 positive women,
      symptomatic cases of HSV infection were minimal, but increased with decreasing
      CD4 count. CONCLUSION: In HIV infected women, the prevalence of HSV antibodies is
      high and symptomatic cases of HSV infection are minimal, but increase with
      decreasing CD4 count. HSV-2 but not HSV-1 was related to sexual behaviour (that
      is, a history of prostitution and the number of sexually active years) in this
      group of HIV infected women.

PMID- 11287692
TI  - Aetiology of urethral discharge in Bangui, Central African Republic.
AB  - OBJECTIVES: To determine the aetiology of urethritis in Bangui, Central African
      Republic. METHODS: 410 men presenting with urethral discharge and 100
      asymptomatic controls were enrolled. Urethral swabs were obtained and processed
      by gonococcal culture and polymerase chain reaction for the detection of
      Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas
      vaginalis, and Ureaplasma urealyticum. RESULTS: In multivariate analyses, M
      genitalium and C trachomatis were significantly associated with urethral
      discharge when comparing cases of non-gonococcal urethritis (NGU) with controls.
      T vaginalis was also more common in cases than in controls, but this reached
      statistical significance only among cases in whom N gonorrhoeae was also
      detected. U urealyticum was not associated with urethritis. The gonococcus was
      found in 69% of cases of urethral discharge. M genitalium was the predominant
      pathogen in patients with NGU, being found in 42% (53/127) of such patients while
      C trachomatis was found in only 17% (22/127). T vaginalis was found in 18%
      (23/127) of patients with NGU, but also in 15% (43/283) of patients with
      gonococcal urethritis, and two thirds of patients with T vaginalis also had the
      gonococcus. Multiple infections were common. M genitalium caused a syndrome
      similar to chlamydial urethritis, with a less severe inflammation than in
      gonococcal infection. No behavioural or clinical characteristic could
      discriminate between the various aetiological agents. CONCLUSIONS: M genitalium
      is more prevalent than C trachomatis and is the most common cause of NGU in
      BANGUI: It causes a syndrome similar to chlamydial urethritis. T vaginalis is
      weakly associated with urethritis, and is often found along with other pathogens.

PMID- 11287694
TI  - Acute neonatal respiratory failure and Chlamydia trachomatis.

PMID- 11287693
TI  - Sexual behaviour of heterosexual individuals with HIV infection naive for
      antiretroviral therapy in Italy.
AB  - BACKGROUND: Specific information about determinants of sexual behaviour of HIV
      infected heterosexuals, like injecting drug use (IDU), are essential to design
      interventions aimed at promoting safer sex practices. METHODS: We analysed data
      on sexual behaviour collected, between March 1997 and March 1999, through a self
      administered questionnaire among 1050 IDUs and 642 non-IDU heterosexuals enrolled
      in a prospective multicentre cohort study on the natural history of HIV
      infection. RESULTS: Among non-IDU heterosexuals, more women (48.5%) than men
      (25.1%) (p<0.001) reported that they were infected by HIV positive regular
      partners whose HIV status they were not aware of. Among the 1119 heterosexual
      males, one fifth reported having had more than 25 sexual partners during their
      lifetime. Condom use in the last sexual intercourse was more common among
      heterosexual IDUs (64.9%) than among non-IDU heterosexual males (58.3%) (p=0.05).
      Heterosexual IDU males were more likely (66.7%) than non-IDU heterosexuals
      (50.6%) to have an HIV negative partner (p<0.001). Of the 573 heterosexual
      females studied, 10.2% reported having had more than 25 lifetime sex partners.
      This proportion was higher among heterosexual IDUs (18.8%) than among non-IDU
      heterosexuals (4.3%) (p<0.001). Nearly 50% of the women in both groups reported
      having used a condom in the last intercourse. Almost 57% of heterosexual IDUs had
      a current HIV negative partner, compared with 34.9% non-IDU heterosexuals
      (p<0.001). In both sexes, the findings from univariate analysis were confirmed by
      multiple logistic regression analysis. CONCLUSIONS: This study identified some
      important differences, in both males and females, in sexual lifestyles according
      to injecting drug use (for example, in terms of HIV negative partners). This
      observation indicates the need to tailor HIV prevention messages according to
      history of injecting drug use.

PMID- 11287696
TI  - Split median raphe: a cause of concern?

PMID- 11287695
TI  - Trovofloxacin for the treatment of chronic granuloma inguinale.

PMID- 11287697
TI  - Why common things are common: the tale of non-gonococcal urethritis.

PMID- 11287698
TI  - Chlamydia trachomatis infection in an urban setting.

PMID- 11287699
TI  - Evolution of Neisseria gonorrhoeae drug susceptibility in Buenos Aires,
      Argentina, 1985-99.

PMID- 11287700
TI  - Uptake of HIV testing in a genitourinary medicine clinic is affected by
      individual doctors.

PMID- 11287703
TI  - Attitudes to lesbians and homosexual men: medical students care.

PMID- 11287704
TI  - Papulonecrotic tuberculide of the glans penis.

PMID- 11287705
TI  - Questionnaires and postal research: more than just high response rates.

PMID- 11287706
TI  - Genital herpes may mask underlying neoplasia.

PMID- 11287707
TI  - Deterioration of disseminated cutaneous Mycobacterium avium complex infection
      with a leukaemoid reaction following institution of highly active antiretroviral
      therapy.

PMID- 11287708
TI  - Sexually shared infections.

PMID- 11287710
TI  - Detection or treatment: which outcome measure?

PMID- 11287712
TI  - Assessment of the functional significance of coronary lesions using a monorail
      catheter.
AB  - Myocardial fractional flow reserve (FFR) < 0.75 is a reliable index of a
      functionally severe coronary stenosis. FFR is best assessed by a sensor-tipped
      pressure monitoring guidewire (PW). The purpose of this study was to assess
      whether a multifunctional probing catheter (MFP), a 3 French dual-lumen monorail
      catheter, can be used to accurately measure intracoronary pressure and FFR. In 35
      lesions (35 patients; learning group), we calculated FFR by both PW (FFRPW) and
      MFP (FFRMFP). Using ROC analysis, the FFRMFP value of 0.65 had the highest
      sensitivity with the FFRPW < 0.75. FFRMFP cut-off (0.65) was tested in 40
      patients (testing group). In all cases, lumen diameter was documented by an
      intracoronary ultrasound examination. In the learning group, the FFRPW was 0.82
      +/- 0.17 and FFRMFP was 0.70 +/- 0.23 (r = 0.88; p < 0.001). The FFRMFP cut-off
      value (0.65) correctly predicted the FFRPW in 37/40 cases in the testing group.
      In the 3 discordant cases, FFR was critical (< 0.65) by MFP and normal (> 0.75)
      by PW. In all these cases, minimal lumen cross-sectional area was < 2.8 mm2. When
      FFRMFP is > 0.65, FFRPW is always > 0.75. These data demonstrate that even with
      larger cross-sectional area than a pressure wire, the MFP catheter can easily and
      reliably be used to assess the functional severity of coronary stenosis.

PMID- 11287711
TI  - Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary
      intervention.
AB  - Randomized controlled trials of patients with non-ST segment elevation acute
      coronary syndromes have established the superiority of enoxaparin (versus
      unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore,
      adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is
      associated with improved clinical outcomes. Since algorithms for integrating
      these pharmacotherapies have not been determined, patients undergoing elective
      PCI were enrolled into 2 distinct and separate studies conducted by the National
      Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4
      studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously
      (without abciximab) and those enrolled in NICE 4 were administered a reduced dose
      (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab
      intravenously during PCI. Bleeding events and ischemic outcomes assessed in
      hospital and at 30-days post-PCI were infrequent with either pharmacologic
      regimen. In the dose regimens studied, enoxaparin with or without abciximab
      appears to provide safe and effective anticoagulation during PCI. The combination
      of reduced-dose enoxaparin and abciximab was associated with a low incidence of
      adverse outcomes (bleeding or ischemic events). Additional studies may be
      required to establish the relative safety and efficacy of this new adjunctive
      pharmacologic strategy when compared with the combination of low-dose, weight
      adjusted unfractionated heparin and abciximab.

PMID- 11287713
TI  - Probing fractional flow reserve.

PMID- 11287714
TI  - Primary angioplasty in acute inferior myocardial infarction with anomalous-origin
      right coronary arteries as infarct-related arteries: focus on anatomic and
      clinical features, outcomes, selection of guiding catheters and management.
AB  - BACKGROUND: Inferior wall myocardial infarction caused by obstruction of an
      anomalous-origin right coronary artery (RCA) is a rare angiographic finding;
      primary angioplasty to an anomalous-origin RCA has never been reported. METHODS:
      In 185 patients with acute inferior wall myocardial infarction resulting from RCA
      occlusion who underwent primary angioplasty, eight patients (4.3%) had anomalous
      origin RCAs. RESULTS: Coronary angiography showed that all 8 patients had a
      dominant RCA. Six patients (75%) had an anomalous-origin RCA arising from the
      anterior aspect of the ascending aorta above the sinotubular line and the other 2
      patients (25%) had an anomalous-origin RCA arising from the left sinus of
      Valsalva with a separate ostium from the left main coronary artery. The standard
      Judkins right guiding catheter did not offer adequate support in these patients.
      In the group of 6 patients, an Amplatz guiding catheter offered good support,
      while a standard Judkins left guiding catheter was adequate in the other 2
      patients. Obstruction of the proximal RCA occurred in 6 patients (75%).
      Successful reperfusion was achieved in 6 patients (75%), resulting in an
      uneventful clinical course and long-term survival (mean follow-up, 24.9 +/- 16.5
      months). Two patients (25%) had unsuccessful reperfusion and died from
      cardiogenic shock. CONCLUSIONS: In this small series, anomalous-origin RCAs were
      the dominant artery and predisposed to atherosclerosis at the proximal portions.
      We suggest that appropriate guide catheter selection and careful manipulation are
      essential for the success of revascularization. Complete reperfusion results in
      an excellent clinical and long-term outcome in patients with anomalous-origin
      RCAs.

PMID- 11287716
TI  - Transcatheter closure of patent ductus arteriosus with the Amplatzer duct
      occluder: short-term follow-up.
AB  - BACKGROUND: Transcatheter closure of the patent ductus arteriosus is a well
      established procedure. The objective of this study was to assess the
      effectiveness and the safety of the Amplatzer duct occluder. METHODS AND RESULTS:
      Occlusion of the patent ductus arteriosus was attempted in 23 patients. The
      median weight was 11.7 Kg (range, 5 kg - 42.4 kg) with a mean ductus diameter of
      3.7 mm (range, 1.6 - 7.2 mm). The immediate closure rate was 86% with a closure
      rate of 100% at 6 months, 1 year and 2 years following device placement. There
      was one device embolization that occurred immediately following device placement.
      No patient had aortic narrowing or pulmonary artery stenosis following the
      procedure. CONCLUSIONS: The Amplatzer duct occluder is safe and effective in the
      closure of a patent ductus arteriosus up to 7.2 mm in diameter. Selecting a
      device at least 12 mm larger than the minimal ductal diameter can minimize
      embolization.

PMID- 11287717
TI  - Transcatheter closure of moderate to large patent ductus arteriosus.

PMID- 11287718
TI  - Transcatheter treatment of IVC channel obstruction and baffle leak after Mustard
      procedure for d-transposition of the great arteries using Amplatzer ASD device
      and multiple stents.
AB  - A patient with d-transposition of the great arteries who underwent the Mustard
      operation at one year of age developed intermittent symptomatic cyanosis as a
      young adult. Evaluation demonstrated a large baffle leak with bidirectional flow
      and stenosis of the intra-atrial IVC baffle channel. Initially, a single stent
      was placed to relieve the obstruction, followed by placement of an Amplatzer
      septal occluder device which assumed suboptimal position after release. Placement
      of additional stents securely repositioned the ASD device into excellent
      position, resulting in complete occlusion of the baffle leak and no residual
      obstruction in the IVC channel.

PMID- 11287719
TI  - Transhepatic catheterization: its role in pediatric cardiac practice.

PMID- 11287720
TI  - An unusual complication of metallic balloon shaft fracture during coronary
      angioplasty.
AB  - We describe two cases of metallic balloon catheter shaft fracture, at a site just
      proximal to the hemostatic Y-adapter, while attempting to push the stent-balloon
      assembly through a tortuous left circumflex artery. In both instances, the stent
      carrying the balloon catheter had a stainless-steel hypotube constituting the
      proximal stiff portion of the shaft. While no inferences pertaining to this
      design can be made, our cases call for a closer observation. It would probably be
      prudent to change the catheter or the dilatation strategy once the shaft started
      buckling.

PMID- 11287721
TI  - Aortic arch (pseudo) aneurysm complicating cardiac catheterization.
AB  - The development of an infected aortic (pseudo)aneurysm which occurred after
      placement of a coronary artery stent is reported. Complications of cardiac
      catheterization and coronary artery stent placement are infrequent and this
      complication has not yet been reported in the literature.

PMID- 11287722
TI  - Multivessel spasm during coronary and peripheral angiography.
AB  - The development of an infected aortic (pseudo)aneurysm which occurred after
      placement of a coronary artery stent is reported. Complications of cardiac
      catheterization and coronary artery stent placement are infrequent and this
      complication has not yet been reported in the literature.

PMID- 11287723
TI  - Avoiding complications of catheter ablation: a review of the current state of the
      art.
AB  - Radiofrequency catheter ablation (RFA) has emerged as a common therapeutic option
      for cardiac arrhythmias. Although tremendous strides have been made to improve
      the efficacy and safety of this procedure, adverse outcomes are still an
      unfortunate reality. The goal of this review is to point out the most common
      pitfalls of RFA and offer guidelines on how to minimize the risks.

PMID- 11287724
TI  - Catheter-based therapeutic angiogenesis: fluoroscopic versus electromechanical
      mapping and guidance.

PMID- 11287725
TI  - Lessons learned from human gene therapy in patients with chronic critical limb
      ischemia.

PMID- 11287726
TI  - Preclinical and clinical experience in vascular gene therapy: advantages over
      conservative/standard therapy.
AB  - No systemic pharmacological treatment has been shown to convincingly reduce the
      incidence of restenosis after angioplasty or increase the formation of
      collaterals in ischemic tissue in patients. The lack of success of many
      pharmaceutical agents in reducing restenosis rates or in inducing angiogenesis
      post-angioplasty and following stent implantation has encouraged the development
      of new technological treatment approaches. Gene therapy is a novel strategy with
      the potential to prevent some of the sequelae after arterial injury, particularly
      cell proliferation, and to induce growth of new vessels or remodeling of pre
      existing vessel branches, which may help patients with critical ischemia. Gene
      therapy strategies have the advantage of minimizing systemic side effects and may
      have a long-term effect as the encoded protein is released. Most clinical trials
      investigating gene therapy for vascular disease have been uncontrolled phase I
      and IIa trials. Gene therapy into vessels with the genes for growth factors has
      been demonstrated to be feasible and efficient. Local drug delivery devices have
      been used in combination with gene therapy in several trials to maximize safety
      and efficiency. Data from experimental animal work indicates that gene therapy
      may modify intimal hyperplasia after arterial injury, but there are few clinical
      trials on restenosis in patients. Preliminary clinical results show only limited
      success in altering restenosis rates. In vitro and experimental in vivo
      investigations into gene therapy for angiogenesis demonstrate increased formation
      of collaterals and functional improvement of limb ischemia. There is some
      evidence of increased collateral formation and clinical improvement in patients
      with critical limb ischemia. Results of placebo-controlled and double-blind
      trials of gene therapy for vascular disease are awaited.

PMID- 11287727
TI  - Perspectives on selective retroinfusion of coronary veins as an alternative
      approach for myocardial gene transfer and angiogenesis.

PMID- 11287728
TI  - Interview with Fayaz A. Shawl, MD by Laurie Gustafson.

PMID- 11287729
TI  - Molecular biology of Alzheimer's dementia and its clinical relevance to early
      diagnosis and new therapeutic strategies.
AB  - Over the past few years, molecular biological research has considerably deepened
      our understanding of the pathophysiological basis of Alzheimer's dementia (AD).
      Although different genetic origins of the disease have been identified, all of
      the findings point to a common terminal sequence in familial AD. This consists of
      an increased production of beta-amyloid peptides from beta-amyloid precursor
      protein. For the cases of sporadic AD, which far outweigh the number of cases of
      familial AD, an impaired catabolism of the beta-amyloid peptides may also be
      pathophysiologically decisive according to the latest findings. Research into the
      molecular level of AD makes it possible to identify points of attack for rational
      drug treatment of the disease, while molecular markers of AD are increasingly
      being used as a part of early and differential neurochemical diagnostics.

PMID- 11287730
TI  - Alleviating constipation in the elderly improves lower urinary tract symptoms.
AB  - BACKGROUND: Constipation and lower urinary tract symptoms (LUTS) very frequently
      occur in the elderly, and several reports have suggested that dysfunction in
      either one of these systems may affect the other. Most studies correlating rectal
      and bladder dysfunction, however, have been carried out in children or young
      women. OBJECTIVE: To examine the effect of alleviating constipation on LUTS in
      the elderly. METHODS: Fifty-two patients aged 65-89 (mean 72 +/- 13) years with
      chronic constipation and LUTS participated in this prospective cohort study.
      Before treatment of constipation was initiated and on their monthly visits,
      patients completed a questionnaire regarding their constipation pattern, urinary
      symptoms, sexual function and mood, and underwent urinalysis. Urinary tract
      anatomy and residual urine were evaluated by abdominal ultrasound at the
      commencement and completion of the study. Patients were followed up for 4 months.
      RESULTS: Treatment of constipation increased the number of weekly defecations
      from 1.5 +/- 0.9 to 4.7 +/- 1.2 (p < 0.001). Patients spent less time on the
      toilet (25 +/- 2.1 versus 63 +/- 1.9 min, p < 0.0001). Fewer patients reported
      urgency (16 versus 34, p < 0.001), frequency (25 versus 47, p < 0.001) and
      burning sensation during urination (6 versus 17, p < 0.05). There was improvement
      in the scoring of urgency, frequency and burning sensation (from a baseline of 52
      to 126, 131 and 95, respectively, p < 0.001). Urinary stream disturbances
      improved in 32 of the 52 patients (p < 0.001). Residual urine volume decreased
      from 85 +/- 39.5 to 30 +/- 22.56 ml (p < 0.001). There was also a significant
      decrease in the number of patients with bacteriurial events (5 versus 17, p <
      0.001), and an improvement in sexual activity and mood (p < 0.05). CONCLUSIONS:
      Our data demonstrated that medical relief of constipation significantly improves
      LUTS in the elderly which, in turn, improves the patient's mood, sexual activity
      and quality of life.

PMID- 11287731
TI  - Elevation of serum hyaluronan level in Werner's syndrome.
AB  - BACKGROUND: There is a well-established association between Werner's syndrome
      (WS) and hyperhyaluronic aciduria; however, to date hyaluronan (HA) in the serum
      has not been statistically linked with WS. Recently, the gene that causes WS has
      been defined as a DNA helicase on chromosome 8, and 19 different mutations in WS
      patients have been identified. It is not known whether the mutation type of the
      Werner helicase gene affects the levels of serum and urine HA in WS patients.
      OBJECTIVE: To evaluate the association of serum HA with WS, and the relationship
      of the serum and urine HA levels to the mutation type. METHODS: HA both in the
      serum and the urine was measured in 40 patients with WS and 114 normal controls.
      The serum and urine HA were quantified by sandwich binding protein assay and
      competitive ELISA-like method, respectively. The muation on WS helicase gene was
      analyzed by mutant-allele-specific amplification and oligomer ligation assay.
      RESULTS: WS patients showed significantly higher levels of HA in the serum (mean
      +/- SD: 115.7 +/- 119.8 ng/ml, p < 0.001) and urine (1,040.8 +/- 777.3 ng/mg
      creatinine, Cre, p < 0.001) than age-matched controls (serum HA: 15.8 +/- 14.2
      ng/ml, urine HA: 379.7 +/- 124.2 ng/mg Cre). The serum and urine HA levels of WS
      patients are almost equal to those of normal controls over 80 years (serum HA:
      118.5 +/- 108.4 ng/ml, urine HA: 914.5 +/- 712.1 ng/mg Cre). There was a
      significant correlation between serum and urine HA levels in WS patients (r =
      0.42, p = 0.007). Analysis of the mutation on the helicase gene in 22 WS patients
      showed that among 44 chromosomes, 3 (6.8%) chromosomes had type 1 mutation, 22
      (50.0%) had type 4 mutation, 14 (31.8%) had type 6 mutation, and the rest had
      other mutations. The serum and urine levels of HA did not show any significant
      association with the mutation type. CONCLUSION: The hyperhyaluronic aciduria in
      WS reflects the high level of serum HA. The serum and urine HA levels are useful
      biochemical markers for WS irrespective of the muation type of the Werner
      helicase gene.

PMID- 11287732
TI  - Telemedicine: a pilot study in nursing home residents.
AB  - BACKGROUND: Telemedicine has been applied successfully in various fields of
      medicine. This mode of health care delivery may potentially be useful in
      supporting frail nursing home residents who require multidisciplinary geriatric
      services. OBJECTIVE: To assess the feasibility of telemedicine in providing
      geriatric services to nursing home residents, and whether this mode of care
      resulted in increased productivity and savings. METHODS: A local 200-bed nursing
      home supported by the Community Geriatric Assessment Team (CGAT) was recruited.
      Over a 1-year period, teleconferencing was used to replace conventional geriatric
      outreach services. The feasibility of telemedicine was evaluated by participating
      specialists. Productivity gains, consumption of hospital services and user
      satisfaction were measured. RESULTS: Telemedicine was adequate for service
      delivery in up to 99% of cases, depending on the specialty. A greater number of
      clients were served and follow-up intervals were shortened. The service was
      cheaper than conventional outreach or clinic activities, and acceptable to users
      and clients. In particular, savings were made through a 9% reduction in visits to
      the Accidents and Emergency Department and in 11% fewer admissions to acute
      hospital wards. CONCLUSION: telemedicine is a feasible means of delivering
      multidisciplinary care to frail nursing home residents, and may result in
      increased productivity and significant savings.

PMID- 11287733
TI  - Age-dependent changes of serum oxygen radical scavenger capacity and haemoglobin
      glycosylation in non-insulin-dependent diabetic patients.
AB  - BACKGROUND: Contradictory results have been reported in the literature concerning
      the correlation between glycosylated haemoglobin (HbA1c) and peroxidation level
      in serum of diabetic patients. OBJECTIVE: To evaluate this correlation in type 2
      diabetic patients by comparing the level of HbA1c with the oxygen radical
      absorbance capacity (ORAC(OH)) of serum. METHODS: One hundred and five type 2
      diabetic patients were enrolled for the study. After having obtained informed
      consent, venous blood samples were drawn after overnight fast at the time of
      routine diabetic check-ups. The blood was collected in plain and EDTA (1 mg/ml)
      tubes. Glycosylated haemoglobin (HbA1c) was determined by cation-exchange
      chromatography (HPLC), and spectrophotometric detection (Diamat Analyzer,
      BioRad). Serum was used for biochemical determinations performed by standard
      laboratory procedures and for ORAC(OH) analysis. This last parameter was
      determined measuring the loss of beta-phycoerytrin fluorescence due to oxidation
      by hydroxyl radicals generated by Cu(2+) and H(2)O(2), in the presence and
      absence of serum. Seventy-eight control age-matched subjects were obtained from
      the personnel staff of our Research Department and old healthy subjects, selected
      on the basis of Senieur Protocol, were relatives of the above mentioned
      personnel. RESULTS: When the population of diabetic patients was taken as a
      whole, a decrease of ORAC(OH) has been observed compared to the controls.
      Moreover, negative correlations were found comparing ORAC(OH) either with HbA1c
      (r = -0.213; p = 0.029) and with the age of patients (r = -0.27; p = 0.005). To
      better understand the effect of age, the data were re-examined dividing the
      diabetics into two populations, i.e. under and over 65 years of age. An age
      dependent decrease of ORAC(OH) and an increase in HbA1c levels has been observed
      comparing these two populations; however, the correlation between the two
      parameters remained statistically significant only in the oldest group (r = 
      0.31; p = 0.026). CONCLUSIONS: Present data point to an involvement of oxidative
      stress in the glycation of haemoglobin especially in old diabetic patients, and
      provide support for the potential use of an antioxidant therapy in these
      patients, irrespective of their glycaemic control.

PMID- 11287734
TI  - Superficial siderosis of the central nervous system: a 70-year-old man with
      ataxia, depression and visual deficits.
AB  - BACKGROUND: Superficial siderosis of the central nervous system (SSNS) is caused
      by cerebral, cerebellar and spinal cord tissue deposition of hemosiderin, often
      related to repeated episodes of subarachnoid hemorrhage. Typical symptoms include
      ataxia, sensorineural deafness and dementia. METHODS AND RESULTS: An elderly
      patient with SSNS presenting with ataxia, depression and severe visual impairment
      was admitted to the Unit of Geriatrics of the University Hospital of Perugia,
      Italy. Late diagnosis and the association of symptoms with SSNS prevented the
      possible surgical treatment of the disease. CONCLUSIONS: Recognition of uncommon
      clinical variants may facilitate early diagnosis of SSNS and improve therapeutic
      results.

PMID- 11287735
TI  - What was the disease of the legs that afflicted King Asa?
AB  - BACKGROUND/OBJECTIVE: The elderly have suffered from pain in their legs, which
      may be associated with various diseases, for thousands of years. This report
      analyzes the disease that afflicted the biblical King Asa (the third king of the
      house of Judah who reigned between 867 and 906 BCE). RESULTS: The sentence
      'Nevertheless in the time of his old age he was diseased in his legs' indicates
      that King Asa suffered from disease in his legs. Among numerous diseases,
      peripheral vascular disease, gout, and degenerative osteoarthritis were most
      likely to affect the King's legs. And among these diseases, the diagnosis of
      peripheral vascular disease is the most acceptable. CONCLUSION: This report shows
      that the roots of contemporary modern gerontology can be traced back to biblical
      times.

PMID- 11287736
TI  - Short-term fluctuations in elderly people's sensorimotor functioning predict text
      and spatial memory performance: The Macarthur Successful Aging Studies.
AB  - BACKGROUND: While age-related increases of between-person variability in a
      variety of cognitive measures are commonly reported in cross-sectional studies,
      the nature of short-term intraindividual fluctuation in elderly people's
      performance is relatively unexplored. OBJECTIVE: The goal of the present study is
      to examine short-term fluctuations in elderly people's sensorimotor functioning
      and their relations to individual differences in verbal and spatial memory.
      METHODS: Fluctuations in old adults' (mean = 75.71 years, SD = 6.93 years)
      sensorimotor performance were investigated by biweekly measurements spanning
      approximately 7 months. Sensorimotor performance was measured by three walking
      tasks, including the duration and the number of steps taken to walk a 360-degree
      circle and to walk 10 feet both at normal and fast pace. Performances of verbal
      and spatial memory were assessed by weekly measurements of digit memory span,
      memory for short text and spatial recognition. RESULTS: The magnitude of
      intraindividual fluctuation in most sensorimotor and memory tasks examined was at
      least half as great as the level of individual differences across persons. In
      addition, intraindividual fluctuation in sensorimotor performance is a relatively
      stable individual attribute, which correlates positively with age and negatively
      with the levels of sensorimotor, text and spatial memory performance. Although a
      substantial amount of individual differences in intraindividual fluctuation was
      shared with mean performance level, variance component and hierarchical
      regression analyses showed that intraindividual fluctuation in walking steps
      added significant independent contribution over and above that given by level of
      performance in predicting text and spatial memory. CONCLUSION: Taking these
      results together, we suggest that intraindividual fluctuations in elderly
      people's performance should not be ignored or simply treated as measurement
      error; rather, they are potentially important empirical variables for
      understanding sensory and cognitive aging and the nature of intraindividual
      response variations in general.

PMID- 11287737
TI  - Epidemiology of hepatitis C virus infection in the elderly.

PMID- 11287739
TI  - Testing quantitative traits for association and linkage in the presence or
      absence of parental data.
AB  - Zhu and Elston developed a transmission disequilibrium test for quantitative
      traits by defining a linear transformation to condition out founder information.
      The method tests the null hypothesis of no linkage or association and can be
      applied to general pedigree structures. However, this method requires both
      genotype and phenotype parental information, which may be difficult to obtain. In
      this paper, we describe parametric and non-parametric methods to relax this
      requirement when only nuclear families are sampled. We show that neither method
      is affected by population stratification in the absence of linkage. The
      statistical power and validity of the tests are investigated by simulation. A
      simple simulation method to calculate the power of the nonparametric method is
      also discussed. In practice, the data may have some families with parental
      phenotype and genotype information available and some without. We briefly discuss
      how all the data may be analyzed jointly.

PMID- 11287740
TI  - Effects of implicit parameters in segregation analysis.
AB  - In human genetic analysis, data are collected through the so-called
      'ascertainment procedure'. Statistically this sampling scheme can be thought of
      as a multistage sampling method. At the first stage, one or several probands are
      ascertained. At the subsequent stages, a sequential sampling scheme is applied.
      Sampling in such a way is virtually a nonrandom procedure, which, in most cases,
      causes biased estimation which may be intractable. This paper focuses on the
      underlying causes of the intractability problem of ascertained genetic data.
      Three types of parameters, i.e. target, design and nuisance parameters, are
      defined as the essences to formulate the true likelihood of a set of data. These
      parameters are also classified into explicit or implicit parameters depending on
      whether they can be expressed explicity in the likelihood function. For
      ascertained genetic data, a sequential scheme is regarded as an implicit design
      parameter, and a true pedigree structure as an implicit nuisance parameter. The
      intractability problem is attributed to loss of information of any implicit
      parameter in likelihood formulation. Several approaches to build a likelihood for
      estimation of the segregation ratio when only an observed pedigree structure is
      available are proposed.

PMID- 11287741
TI  - Power to detect linkage based on multiple sets of data in the presence of locus
      heterogeneity: comparative evaluation of model-based linkage methods for affected
      sib pair data.
AB  - The development of rigorous methods for evaluating the overall strength of
      evidence for genetic linkage based on multiple sets of data is becoming
      increasingly important in connection with genomic screens for complex disorders.
      We consider here what happens when we attempt to increase power to detect linkage
      by pooling multiple independently collected sets of families under conditions of
      variable levels of locus heterogeneity across samples. We show that power can be
      substantially reduced in pooled samples when compared to the most informative
      constituent subsamples considered alone, in spite of the increased sample size
      afforded by pooling. We demonstrate that for affected sib pair data, a simple
      adaptation of the lod score (which we call the compound lod), which allows for
      intersample admixture differences can afford appreciably higher power than the
      ordinary heterogeneity lod; and also, that a statistic we have proposed
      elsewhere, the posterior probability of linkage, performs at least as well as the
      compound lod while having considerable computational advantages. The companion
      paper (this issue, pp 217-225) shows further that in application to multiple data
      sets, familiar model-free methods are in some sense equivalent to ordinary lod
      scores based on data pooling, and that they therefore will also suffer dramatic
      losses in power for pooled data in the presence of locus heterogeneity and other
      complicating factors.

PMID- 11287742
TI  - Offspring risk and sibling risk for multilocus traits.
AB  - The recurrence risk of a trait in a relative of type R is the probability that an
      individual who is in relationship of type R to an affected proband has the trait.
      It is intuitively clear that closer relationships lead to higher recurrence
      risks. However, no exact analysis of this phenomenon has been presented for
      multilocus traits. We prove a theorem that shows how recurrence risks are
      influenced by the degree of closeness of the relationship R. For example, our
      theorem implies that sibling risk is always higher than offspring risk. The loci
      influencing the trait are assumed to be autosomal and unlinked, but arbitrary
      epistasis between the loci is allowed. We give a detailed proof of the theorem by
      using stochastic matrices. A shorter proof based on the additive and dominance
      genetic variances is also sketched. Additionally, we also give some empirical
      results and discuss generalizations of the theorem.

PMID- 11287743
TI  - Comparison of 'model-free' and 'model-based' linkage statistics in the presence
      of locus heterogeneity: single data set and multiple data set applications.
AB  - Earlier work [Knapp et al.: Hum Hered 1994;44:44-51] focusing on affected sib
      pair (ASP) data established the equivalence between the mean test and a test
      based on a simple recessive lod score, as well as equivalences between certain
      forms of the maximum likelihood score (MLS) statistic [Risch: Am J Hum Genet
      1990;46:242-253] and particular forms of the lod score. Here we extend the
      results of Knapp et al. [1994] by reconsidering these equivalences for ASP data,
      but in the presence of locus heterogeneity. We show that Risch's MLS statistic
      under the possible triangle constraints [Holmans: Am J Hum Genet 1993;52:362-374]
      is locally equivalent to the ordinary heterogeneity lod score assuming a simple
      recessive model (HLOD/R); while the one-parameter MLS assuming no dominance
      variance is locally equivalent to the (homogeneity) recessive lod. The companion
      paper (this issue, pp 199-208) showed that when considering multiple data sets in
      the presence of locus heterogeneity, the HLOD can suffer appreciable losses in
      power. We show here that in ASP data, these equivalences ensure that this same
      loss in power is incurred by both forms of the MLS statistic as well. The
      companion paper also introduced an adaptation of the lod, the compound lod score
      (HLOD/C). We confirm that the HLOD/C maintains higher power than these 'model
      free' methods when applied to multiple heterogeneous data sets, even when it is
      calculated assuming the wrong genetic model.

PMID- 11287744
TI  - Rapid multipoint linkage analysis via inheritance vectors in the Elston-Stewart
      algorithm.
AB  - The calculation of multipoint likelihoods of pedigree data is crucial for
      extracting the full available information needed for both parametric and
      nonparametric linkage analysis. Recent mathematical advances in both the Elston
      Stewart and Lander-Green algorithms for computing exact multipoint likelihoods of
      pedigree data have enabled researchers to analyze data sets containing more
      markers and more individuals both faster and more efficiently. This paper
      presents novel algorithms that further extend the computational boundary of the
      Elston-Stewart algorithm. They have been implemented into the software package
      VITESSE v. 2 and are shown to be several orders of magnitude faster than the
      original implementation of the Elston-Stewart algorithm in VITESSE v. 1 on a
      variety of real pedigree data. VITESSE v. 2 was faster by a factor ranging from
      168 to over 1,700 on these data sets, thus making a qualitative difference in the
      analysis. The main algorithm is based on the faster computation of the
      conditional probability of a component nuclear family within the pedigree by
      summing over the joint genotypes of the children instead of the parents as done
      in the VITESSE v. 1. This change in summation allows the parent-child
      transmission part of the calculation to be not only computed for each parent
      separately, but also for each locus separately by using inheritance vectors as is
      done in the Lander-Green algorithm. Computing both of these separately can lead
      to substantial computational savings. The use of inheritance vectors in the
      nuclear family calculation represents a partial synthesis of the techniques of
      the Lander-Green algorithm into the Elston-Stewart algorithm. In addition, the
      technique of local set recoding is introduced to further reduce the complexity of
      the nuclear family computation. These new algorithms, however, are not
      universally faster on all types of pedigree data compared to the method
      implemented in VITESSE v. 1 of summing over the parents. Therefore, a hybrid
      algorithm is introduced which combines the strength of both summation methods by
      using a numerical heuristic to decide which of the two to use for a given nuclear
      family within the pedigree and is shown to be faster than either method on its
      own. Finally, this paper discusses various complexity issues regarding both the
      Elston-Stewart and Lander-Green algorithms and possible future directions of
      further synthesis.

PMID- 11287745
TI  - Genistein effects on growth and cell cycle of Candida albicans.
AB  - Microbial virulence is generally considered to be multifactorial with infection
      resulting from the sum of several globally regulated virulence factors. Estrogen
      may serve as a signal for global virulence induction in Candida albicans.
      Nonsteroidal estrogens and estrogen receptor antagonists may therefore have
      interesting effects on yeast and their virulence factors. Growth of C. albicans
      was monitored by viable plate counts at timed intervals after inoculation into
      yeast nitrogen broth plus glucose. To determine if increased growth of yeast in
      the presence of estradiol was due to tyrosine kinase-mediated signaling, we
      measured growth in the presence of genistein, estradiol or genistein plus
      estradiol and compared these conditions to controls, which were not supplemented
      with either compound. Unexpectedly, genistein stimulated growth of C. albicans.
      In addition, genistein was found to increase the rate of germination (possibly
      reflecting release from G(0) into G(1) cell cycle phase) and also increased Hsp90
      expression, demonstrated by a dot blot technique which employed a commercial
      primary antibody detected with chemiluminescence with horseradish peroxidase
      labeled secondary antibody. These biological effects may be attributable to
      genistein's activity as a phytoestrogen. In contrast, nafoxidine suppressed
      growth of Candida and mildly diminished Hsp90 expression. This study raises the
      possibility of receptor cross-talk between estrogen and isoflavinoid compounds,
      and antiestrogens which may affect the same signaling system, though separate
      targets for each compound were not ruled out.

PMID- 11287746
TI  - The role of RsmA in the regulation of swarming motility in Serratia marcescens.
AB  - Swarming motility is a multicellular phenomenon comprising population migration
      across surfaces by specially differentiated cells. In Serratia marcescens, a
      network exists in which the flhDC flagellar regulatory master operon,
      temperature, nutrient status, and quorum sensing all contribute to the regulation
      of swarming motility. In this study, the rsmA (repressor of secondary
      metabolites) gene (hereafter rsmA(Sm)) was cloned from S. marcescens. The
      presence of multicopy, plasmid-encoded rsmA(Sm) expressed from its native
      promoter in S. marcescens inhibits swarming. Synthesis of N-acylhomoserine
      lactones, presumably by the product of smaI (a luxI homolog isolated from S.
      marcescens), was also inhibited. Knockout of rsmA(Sm) on the S. marcescens
      chromosome shortens the time before swarming motility begins after inoculation to
      an agar surface. A single copy of the chromosomal PrsmA(Sm)::luxAB reporter of
      rsmA(Sm) transcription was constructed. Using this reporter, the roles of the
      flhDC flagellar regulatory master operon, temperature and autoregulation in the
      control of rsmA(Sm) expression were determined. Our findings indicate that
      RsmA(Sm) is a component of the complex regulatory network that controls swarming.

PMID- 11287748
TI  - Regulation of thymidine kinase expression during cellular senescence.
AB  - As human diploid fibroblasts (HDFs) in culture senesce, the expression of
      thymidine kinase (TK) and the activity of its promoter become attenuated. Herein
      we analyze the cis-elements involved in transcriptional activation of the hTK
      promoter, and show that the Sp1 binding site located at -118/-113 and one CCAAT
      box located at either -71/-67 or -40/-36 are critical for maximal expression of
      hTK promoter activity in young IMR-90 HDFs. However, the DNA binding activities
      to TK-CCAAT and Sp1 were not defective in serum-stimulated senescent HDFs. On the
      other hand, treatment of young HDFs during the late G1 transition with a specific
      inhibitor of CDK2, roscovitine, blocked the induction of TK RNA expression.
      Because CDK2 remained inactive during serum stimulation in senescent HDFs, it is
      likely that the impairment of TK expression in senescent HDFs during serum
      stimulation is relevant to the inactivation of CDK2, rather than to the
      controlling mechanism at the level of NF-Y and Sp1 activity.

PMID- 11287747
TI  - Construction of a tagging system for subcellular localization of proteins encoded
      by open reading frames.
AB  - We have previously characterized a monoclonal antibody (SC1D7) that is directed
      to maltose-binding protein (MBP) of Escherichia coli and other closely related
      enteric bacteria. SC1D7 does not cross-react with proteins in eucaryotes and
      appears to be a highly specific tool in immunochemical analyses. To better map
      the epitope, we took advantage of an available plasmid, pMAL-c2, that encodes the
      E. coli MBP-coding sequence and constructed plasmids to express MBP fragments. A
      construct containing the N-terminal portion of MBP does not react with SC1D7,
      whereas a second construct expressing glutathione S-transferase fused with the C
      terminal half of MBP does react with SC1D7. To precisely define the epitope,
      random peptides displayed on M13 were used to react with SC1D7. Sequences of
      reactive peptides were aligned, and a consensus sequence of XDXRIPX was deduced.
      This sequence matches MBP with an amino acid stretch of KDPRIAA. To consolidate
      the mapping result, a sequence encoding this epitope was inserted into an
      expression vector and the resulting recombinant protein did react with SC1D7.
      Thereafter, this epitope was incorporated into a eucaryotic expression plasmid
      containing a previously defined hepatitis delta virus epitope for protein
      tagging. This two-epitope-tagging vector is useful in various molecular analyses.
      We demonstrate its usage for localization of a bacterial virulence factor in host
      cells. This vector should be applicable for high-throughput characterization of
      new open reading frames found in genome sequencing.

PMID- 11287750
TI  - Gene deletion patterns in spinal muscular atrophy patients with different
      clinical phenotypes.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by
      degeneration of lower motor neurons. We have assayed deletions in two candidate
      genes, the survival motor neuron (SMN) and neuronal apoptosis inhibitory protein
      (NAIP) genes, in 108 samples, of which 46 were from SMA patients, and 62 were
      from unaffected subjects. The SMA patients included 3 from Bahrain, 9 from South
      Africa, 2 from India, 5 from Oman, 1 from Saudi Arabia, and 26 from Kuwait. SMN
      gene exons 7 and 8 were deleted in all type I SMA patients. NAIP gene exons 5 and
      6 were deleted in 22 of 23 type I SMA patients. SMN gene exon 7 was deleted in
      all type II SMA patients while exon 8 was deleted in 19 of 21 type II patients.
      In 1 type II SMA patient, both centromeric and telomeric copies of SMN exon 8
      were deleted. NAIP gene exons 5 and 6 were deleted in only 1 type II SMA patient.
      In 1 of the 2 type III SMA patients, SMN gene exons 7 and 8 were deleted with no
      deletion in the NAIP gene, while in the second patient, deletions were detected
      in both SMN and NAIP genes. None of the 62 unaffected subjects had deletions in
      either the SMN or NAIP gene. The incidence of biallelic polymorphism in SMN gene
      exon 7 (BsmAI) was found to be similar (97%) to that (98%) reported in a Spanish
      population but was significantly different from that reported from Taiwan (0%).
      The incidence of a second polymorphism in SMN gene exon 8 (presence of the
      sequence ATGGCCT) was markedly different in our population (97%) and those
      reported from Spain (50%) and Taiwan (0%).

PMID- 11287749
TI  - Protein kinase C-mediated tyrosine phosphorylation of paxillin and focal adhesion
      kinase requires cytoskeletal integrity and is uncoupled to mitogen-activated
      protein kinase activation in human hepatoma cells.
AB  - Treatment of cultured human hepatoma HepG2 cells with the protein kinase C (PKC)
      activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), results in an increase in
      tyrosine phosphorylation of several proteins, including the focal adhesion kinase
      (FAK) and paxillin using anti-phosphotyrosine Western blotting and
      immunoprecipitation. However, when cells are in suspension or in the presence of
      cytochalasin D which disrupts the intracellular network of actin microfilaments,
      TPA loses its ability to stimulate tyrosine phosphorylation of FAK and paxillin
      but it still activates mitogen-activated protein kinase (MAPK) and induces PKC
      translocation from cytosol to the membrane in HepG2 cells. On the other hand,
      PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, blocks
      TPA-induced MAPK activation but has no effect on TPA-induced tyrosine
      phosphorylation. Our findings suggest that TPA-induced tyrosine phosphorylation
      of FAK and paxillin in human hepatoma cells is PKC dependent and requires the
      integrity of the cell cytoskeleton but is uncoupled to the signal transduction
      pathway of PKC leading to the translocation of PKC and MAPK activation.

PMID- 11287751
TI  - The effect of increased processivity on overall fidelity of human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - We previously reported that two insertions of 15 amino acids in the beta3-beta4
      hairpin loop of fingers subdomain of HIV-1(NL4-3) RT confer an increased
      polymerase processivity. The processivity of human immunodeficiency virus (HIV)
      reverse transcriptase (RT) is thought to influence the fidelity of HIV-1 RT,
      which tends to create errors at template sites with high termination probability.
      Employing the two insertion variants of HIV-1 RT (FE20 and FE103), we examined
      the relationship between processivity, overall fidelity and error specificity.
      Although the overall mutation rate was unaffected by increased processivity, one
      of the mutants, FE103, generated significantly fewer frameshift errors. The other
      mutant, FE20, generated errors at hotspots not previously observed for HIV-1 RT.
      Our results indicate that an increase in the polymerase processivity of HIV-1 RT
      does not necessarily result in a decreased mutation rate and confirm that changes
      in processivity alter the sequence context in which the errors are made.
      Furthermore, our results also reveal that the mutation frequency obtained via in
      vitro gap-filling reactions with wild-type HIV-1(NL4-3) RT is only 2-fold higher
      than that obtained via a single cycle infection assay using the same, wild-type
      HIV-1(NL4-3) RT sequence as part of the helper pol function [Mansky and Temin: J
      Virol 69:5087-5094;1995].

PMID- 11287752
TI  - The expression of HPV-16 E5 protein in squamous neoplastic changes in the uterine
      cervix.
AB  - To investigate the expression of human papillomavirus type 16 (HPV-16) E5 protein
      in squamous neoplastic changes in the uterine cervix, the specific E5 antibody
      was generated and used to identify the expression of E5 protein in 40 cases of
      HPV-16-positive tissues and 5 previously identified HPV-negative normal cervical
      tissues. The results revealed that E5 protein was primarily expressed in the
      lower third of the epithelium in low-grade squamous intraepithelial lesions
      (SILs) and throughout the whole epithelium in high-grade SILs. In invasive
      squamous carcinoma, 60% of HPV-16-infected cancers which contained the episomal
      viral genome had the E5 gene, and could express E5 protein which was located
      throughout the whole epithelium. Previously, we documented the expression of type
      I growth factor receptors [ERBB1/EGFR (epidermal growth factor receptor), ERBB2,
      ERBB3 and ERBB4] in the full range of cervical neoplasias by immunohistochemistry
      assay. Hence, in this study, we extensively analyzed the correlation between the
      expression of E5 protein and the expression of type I growth factor receptors.
      Among 40 HPV-16- infected cervical neoplasias, we found that the expression of E5
      protein was significantly correlated with either the expression of the ERBB1 or
      the ERBB4 receptor.

PMID- 11287753
TI  - Microarray profiling of gene expression patterns in bladder tumor cells treated
      with genistein.
AB  - Microarray technology was used to gain an insight into the molecular events of
      tumor cell growth inhibition mediated by the soy isoflavone genistein. For this,
      a susceptible bladder tumor line TCCSUP was treated with the inhibitory dose (50
      microM) of genistein for various periods of time, followed by mRNA isolations,
      cDNA probe preparations, and hybridization individually to cDNA chips containing
      884 sequence-verified known human genes. After analyzing the hybridization
      signals with a simple quantitative method developed by this study, we detected
      that egr-1, whose expression has been associated with proliferation and
      differentiation, was transiently induced and this expression pattern was later
      confirmed by RT-PCR. Thus, microarray technology is a reliable and powerful tool
      for profiling gene expression patterns in many biological systems related to
      cancer. We further detected many groups of genes with distinct expression
      profiles and most of them encode for proteins that regulate the signal
      transduction or the cell cycle pathways. These genes warrant further
      investigation as regards their roles in the susceptibility of the tumor cell line
      to the antitumor drug.

PMID- 11287754
TI  - Hepatitis E virus DNA vaccine elicits immunologic memory in mice.
AB  - Injection of an expression vector pJHEV containing hepatitis E virus (HEV)
      structural protein open reading frame 2 gene generates a strong antibody response
      in BALB/c mice that can bind to and agglutinate HEV. In this study, we tested for
      immunologic memory in immunized mice whose current levels of IgG to HEV were low
      or undetectable despite 3 doses of HEV DNA vaccine 18 months earlier. Mice
      previously vaccinated with vector alone were controls. All mice were administered
      a dose of HEV DNA vaccine to simulate an infectious challenge with HEV. The
      endpoint was IgG to HEV determined by ELISA. Ten days after the vaccine dose, 5
      of 9 mice previously immunized with HEV DNA vaccine had a slight increase in IgG
      to HEV. By 40 days after the vaccine dose, the level of IgG to HEV had increased
      dramatically in all 9 mice (108-fold increase in geometric mean titer). In
      contrast, no control mice became seropositive. These results indicate that mice
      vaccinated with 3 doses of HEV DNA vaccine retain immunologic memory. In response
      to a small antigenic challenge delivered as DNA, possibly less than delivered by
      a human infective dose of virus, mice with memory were able to generate high
      levels of antibody in less time than the usual incubation period of hepatitis E.
      We speculate that this type of response could protect a human from overt disease.

PMID- 11287755
TI  - Ventricular arrhythmias and sudden cardiac death in end-stage renal disease
      patients on chronic hemodialysis.

PMID- 11287757
TI  - Renal functional reserve in patients with recently diagnosed Type 2 diabetes
      mellitus with and without microalbuminuria.
AB  - BACKGROUND/AIMS: During the first 10 years, two thirds of the patients with type
      2 diabetes mellitus (DM) have microalbuminuria (MA). Functional renal reserve
      (FRR) and its relationship with proteinuria and metabolic control are unknown at
      the early phases of disease. We investigated the frequency of MA in recently
      diagnosed type 2 DM patients, and its association with FRR. METHODS: We studied
      181 type 2 DM patients with less than 6 months since diagnosis. Renal volume, MA,
      glomerular filtration rate (GFR) and renal plasma flow (ERPF) were evaluated
      before and after an acute oral protein load in 28 type 2 DM patients (14 with,
      and 14 without MA), and in 7 healthy subjects. RESULTS: A total of 10.6% of the
      patients had MA. MA patients had higher cholesterol and triglyceride levels than
      those normoalbuminuric. Twenty recently diagnosed type 2 diabetic patients showed
      high basal GFR. Twelve of them had MA and insulin resistance. After the acute
      oral protein load, the control subjects and the patients without MA increased
      their GFR and their ERPF. The group with MA did not. CONCLUSIONS: Seventy-five
      percent of the patients were hyperfiltering. Normoalbuminuric patients had larger
      increase in GFR and ERRPF than MB patients. We conclude that FRR measurement can
      be an important tool for the diagnosis of latent diabetic nephropathy.

PMID- 11287756
TI  - Molecular mechanisms of erythropoietin signaling.
AB  - Erythropoietin is an obligatory growth factor for red blood cell production. The
      receptor for erythropoietin contains a single membrane-spanning domain with no
      intrinsic tyrosine kinase motifs. On binding to erythropoietin, the receptor
      dimerizes and activates multiple intracellular signaling molecules, including but
      not limited to JAK2, STAT5, PI 3-kinase, IRS-2, RAS, and Ca2+ channels. This
      review focuses on cytoplasmic signaling cascades involved in erythropoietin
      action.

PMID- 11287758
TI  - Intraglomerular synthesis of complement C3 and its activation products in IgA
      nephropathy.
AB  - BACKGROUND: Complement activation is thought to be pathologically important in
      IgA nephropathy (IgAN). Although C3 deposition in the mesangium is found in IgAN,
      the origin of C3 is not clear. We recently demonstrated intraglomerular C3
      synthesis in the human kidney; however, the activation and pathological role of
      locally synthesized C3 remains unclear. Here we performed nonradioactive in situ
      hybridization for C3 mRNA and immunohistochemistry for C3 and its activation
      products, such as C3d and membrane attack complex (MAC), to determine whether
      locally produced C3 in glomeruli was activated in IgA nephropathy. METHODS: Renal
      samples from 14 patients with IgAN and 5 with minimal change nephrotic syndrome
      (MCNS) were examined. Uninvolved portions of surgically removed kidneys with
      tumors served as normal controls. RESULTS: C3 mRNA was not detected in glomeruli
      in control tissue and MCNS, but was strongly expressed in resident glomerular
      cells of IgAN, including mesangial cells, glomerular epithelial cells and the
      cells of Bowman's capsule. Examination of serial sections disclosed that more
      than 70% of cells positive for C3 mRNA were also stained for C3 protein, C3d, and
      MAC. Double staining for in situ hybridization and immunohistochemistry also
      revealed that those C3 mRNA signals were present in intraglomerular cells
      positive for C3. The expression of C3 mRNA and MAC in glomeruli correlated
      significantly with the degree of mesangial matrix expansion. CONCLUSIONS: Our
      results demonstrated that locally synthesized C3 is activated in the glomeruli of
      IgAN and that its expression correlated with the severity of mesangial matrix
      expansion. These findings suggest that activation of C3 may be involved in tissue
      injury in IgAN through the formation of membrane attack complex.

PMID- 11287759
TI  - Transforming growth factor-beta(1) and myofibroblasts: a potential pathway
      towards renal scarring in human glomerular disease.
AB  - BACKGROUND/AIMS: The cellular and humoral factors involved in the development and
      progression of renal scarring have not been fully investigated. Transforming
      growth factor-beta (TGF-beta(1)) is considered to be the main fibrogenic growth
      factor and it is implicated in the pathogenesis of renal fibrosis in experimental
      and clinical nephropathies. On the other hand, collagen III is an important
      component of the extracellular matrix. In this study we attempted to identify any
      possible links between TGF-beta(1) and collagen III synthesis and expression with
      the expression of myofibroblasts in the evolution of renal scarring in human
      glomerular diseases. METHODS: We studied retrospectively 40 patients with various
      types of primary and secondary glomerulonephritis (GN), with either proliferative
      or nonproliferative pattern, with emphasis on the renal synthesis of TGF-beta(1)
      and collagen III (detected by in situ hybridization) and their expression
      (detected by immunohistochemistry) as well as myofibroblast expression. The
      possible links of TGF-beta(1) expression with myofibroblast distribution (alpha
      smooth muscle actin, alpha-SMA(+) cells) and with conventional histopathology and
      renal function was also examined. RESULTS: TGF-beta(1) protein and mRNA were
      detected in the renal tubular epithelial cells and interstitium and to a lesser
      extent within glomeruli of patients with GN. Collagen III was mainly detected in
      the interstitium (peritubular and periglomerular areas) and to a lesser extent in
      the glomeruli. Messenger RNA for collagen III followed a similar peritubular and
      periglomerular distribution to that of TGF-beta(1) and alpha-SMA(+) interstitial
      cells. The intensity of interstitial TGF-beta(1) protein expression was
      significantly related to the degree of interstitial fibrosis (r = 0.628, p <
      0.01), tubular atrophy (r = 0.612, p < 0.01), interstitial collagen III
      expression (r = 0.478, p < 0.05), and serum creatinine values (r = 0.722, p <
      0.001). Also there was a close positive correlation between the severity of
      interstitial myofibroblast expression and interstitial TGF-beta(1) (r = 0.412, p
      < 0.05), as well as collagen III (r = 0.409, p < 0.05). In addition, a
      significant correlation was found between glomerular TGF-beta(1) expression and
      severity of glomerulosclerosis (r = 0.620, p < 0.01). CONCLUSION: The results of
      this study suggest that TGF-beta(1) plays an important role in the pathogenesis
      of fibrosis developing in human kidney, during the evolution of glomerular
      disease. Interstitial myofibroblasts may contribute to interstitial fibrosis
      through the synthesis and release of both TGF-beta1 and collagen III.

PMID- 11287760
TI  - Polymorphism in methylenetetrahydrofolate reductase gene: its impact on plasma
      homocysteine levels and carotid atherosclerosis in ESRD patients receiving
      hemodialysis.
AB  - The methylenetetrahydrofolate reductase (MTHFR) gene polymorphism has been shown
      to be associated with cardiovascular disease in healthy subjects as well as in
      patients with end-stage renal disease (ESRD). In this study, we examined the
      allelic frequency and genotype distribution of the MTHFR gene in 151 Chinese ESRD
      patients receiving hemodialysis and 135 healthy controls. In addition, we
      investigated the relationship between the MTHFR gene polymorphism and the plasma
      homocysteine (Hcy) level as well as the intima-media thickness of common carotid
      artery (CC-IMT) in these patients. The allelic frequency of the MTHFR gene with
      the C677T mutation in ESRD patients was 24.5% and that in healthy controls was
      23%. Mean plasma Hcy level of the ESRD patients (23.1 +/- 7.4 micromol/l) was
      significantly higher than that of the controls (10.1 +/- 5.0 micromol/l), but did
      not correlate with vitamin B(6) and vitamin B(12) status. Moreover, the extent of
      hyperhomocysteinemia was genetically affected by the C677T mutation of the MTHFR
      gene. The plasma Hcy levels for the patients with the CC, CT and TT genotypes of
      the MTHFR gene were 22.3 +/- 6.8, 22.8 +/- 7.3, and 28.3 +/- 2.8 micromol/l,
      respectively. In addition, we found that the patients bearing the TT genotype had
      the highest CC-IMT (0.93 +/- 0.07 mm), whereas the lowest values (0.79 +/- 0.13
      mm) were observed in those who had the CC genotype. One-way ANOVA showed that the
      CC-IMT in the patients with the TT genotype was significantly greater than that
      of the patients with the CC genotype (p < 0.05). Moreover, the mean CC-IMT of the
      patients carrying either TT or CT genotype of the MTHFR gene was significantly
      higher than that of the patients bearing the CC genotype (0.86 +/- 0.14 vs. 0.79
      +/- 0.13 mm, p = 0.002). Multiple regression analysis, in which the change in CC
      IMT was used as the dependent variables, identified age, smoking, the MTHFR
      genotype (CC = 0, CT = 1, TT = 2) and diabetes mellitus as the independent
      variables significantly associated with the increase of CC-IMT (p < 0.001). These
      risk factors jointly explained 43.9% of the CC-IMT variation and age explained
      most of the variation (R(2) = 0.34). We conclude that both the TT genotype and
      the T allele of the MTHFR gene are associated with the increase of CC-IMT in
      hemodialysis patients. The C677T mutation of the MTHFR gene may be an independent
      risk factor that predicts the development of carotid atherosclerosis in ESRD
      patients.

PMID- 11287761
TI  - Direct effect of the correction of acidosis on plasma parathyroid hormone
      concentrations, calcium and phosphate in hemodialysis patients: a prospective
      study.
AB  - BACKGROUND: Metabolic acidosis contributes to renal osteodystrophy and together
      with hyperphosphatemia, hypocalcemia and altered vitamin D metabolism may result
      in increased levels of intact parathyroid hormone (iPTH) and metastatic
      calcifications. However, the impact of the correction of metabolic acidosis on
      iPTH levels and calcium-phosphate metabolism is still controversial. STUDY
      DESIGN: The effects of the correction of metabolic acidosis on serum
      concentrations of iPTH, calcium (Ca), phosphate (PO(4)) and alkaline phosphatase
      were prospectively studied. Twelve uremic patients on maintenance hemodialysis
      (HD) for 49 months (median; range 6-243 months) with serum bicarbonate levels <
      or =20 mmol/l were studied before and after 3 months of oral sodium bicarbonate
      supplementation. Predialysis serum bicarbonate, arterial pH, ionized calcium,
      plasma sodium, plasma potassium, serum creatinine, hemoglobin, K(t)/V,
      postdialysis body weight, predialysis systolic and diastolic blood pressure were
      also evaluated before and after correction. RESULTS: Serum bicarbonate levels and
      arterial pH increased respectively from 19.3 +/- 0.6 to 24.4 +/- 1.2 mmol/l (p <
      0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (p < 0.001). iPTH levels decreased
      significantly from 399 +/- 475 to 305 +/- 353 pg/ml (p = 0.026). No changes in
      total serum Ca, plasma PO(4), serum akaline phosphatase, K(t)/V, serum
      creatinine, hemoglobin, body weight, predialysis systolic and diastolic blood
      pressures were observed. iCa decreased significantly. CONCLUSIONS: Our study
      demonstrates that the correction of metabolic acidosis in chronic HD patients
      reduces iPTH concentrations in HD patients with secondary hyperparathyroidism
      possibly by a direct effect on iPTH secretion.

PMID- 11287762
TI  - Inhibitory effects of nicorandil on rat mesangial cell proliferation via the
      protein kinase G pathway.
AB  - We investigated the effects of nicorandil, which is a hybrid between a nitrate
      and an ATP-sensitive potassium channel (K(ATP)) opener, on cultured rat mesangial
      cell proliferation. Nicorandil (1 microM to 1 mM inhibited [(3)H]thymidine
      incorporation into rat mesangial cells in a concentration-dependent manner.
      Nicorandil (1 microM to 1 mM) also inhibited the number of cells. Nicorandil
      increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial
      cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition
      of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate
      cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell
      proliferation. We also examined the effects of K(ATP) mediators. Cromakalim, a
      K(ATP) activator, and glibenclamide, a K(ATP) inhibitor, had little effect on the
      proliferation of mesangial cells. These results suggest that the inhibitory
      effects of nicorandil on mesangial cell proliferation are mediated via the
      protein kinase G pathway.

PMID- 11287763
TI  - Cell proliferation/cell death balance in renal cell cultures after exposure to a
      static magnetic field.
AB  - The effect of a static magnetic field (MF) of 0.5 mT of intensity on the cell
      proliferation/cell death balance was investigated in renal cells (VERO) and
      cortical astrocyte cultures from rats. Magnetic stimulation was delivered by
      magnetic disks at known intensities. The percentage of apoptotic and necrotic
      cells was evaluated using flow cytometry and morphological analysis following
      Hoechst chromatin staining. An index of cell proliferation was determined using
      sulfonated tetrazolium (WST-1). Control cultures were prepared without exposure
      to MFs. After 2, 4 and 6 days of exposure to a MF, we observed a gradual decrease
      in apoptosis and proliferation and a gradual increase in cells with a necrotic
      morphology with respect to the control group. In astrocyte cultures, over a 6-day
      exposure period. A gradual increase was observed in apoptotic, proliferating, and
      necrotic cells. Our findings suggest that the effect of exposure to MFs varies,
      depending on the cell type; MFs may also have a nephropathogenic effect.

PMID- 11287764
TI  - Platelet-activating factor antagonist, SM-12502, attenuates experimental
      glomerular thrombosis in rats.
AB  - Platelet-activating factor (PAF) is involved in many pathologic conditions
      through its potent proinflammatory and vasoactive effects. Using a specific PAF
      antagonist, SM-12502, we investigated the role of PAF in rat experimental
      glomerular thrombosis. In this model, sequential injections of nephrotoxic serum
      (NTS) and lipopolysaccharide (LPS) selectively induce glomerular fibrin
      deposition accompanied by neutrophil accumulation. SM-12502, when injected
      simultaneously with either NTS or LPS, strongly inhibited glomerular fibrin
      deposition in a dose-dependent manner. In contrast, neutrophil invasion was
      similar in both SM-12502-injected and uninjected rats, suggesting that the
      antithrombotic effect was not mediated by inhibition of neutrophil migration.
      However, serum myeloperoxidase activity, a marker of neutrophil activation, was
      significantly suppressed by treatment with SM-12502. From a previous finding
      supporting the indispensable role of neutrophils in this model and the current
      observations, SM-12502 is suggested to attenuate glomerular thrombosis by
      inhibiting neutrophil activation. Thus, the present findings suggest an
      involvement of PAF in this glomerular thrombosis model.

PMID- 11287766
TI  - Serum crosslaps correlations with serum ICTP and urine DPD in hemodialyzed and
      peritoneally dialyzed patients.

PMID- 11287765
TI  - Nadroparin-induced Calcinosis cutis in renal transplant recipients.
AB  - Low-molecular-weight heparins are routinely used to prevent deep venous
      thrombosis following renal transplantation in our department. We report 2
      patients who developed tender erythematous subcutaneous nodules with induration,
      ulceration and necrosis at the site of subcutaneous administration of nadroparin.
      Both patients were renal transplant recipients with impaired graft function and
      high serum calcium-phosphate products. The diagnosis calcinosis cutis was
      confirmed by technetium-99m bone scan and by histological examination of
      biopsies. Both patients showed spontaneous recovery several weeks after
      discontinuation of nadroparin. Patients with chronic renal failure and
      hyperphosphatemia may be predisposed to develop calcinosis cutis. In addition,
      the role of the calcium content of nadroparin is discussed.

PMID- 11287767
TI  - Overall no adverse effect of a single session of hemodialysis on hearing
      abilities.

PMID- 11287768
TI  - Glycosuria in alcoholics. Alcohol diabetes, transient hyperglycemia, renal
      tubular syndrome or factitious dipstick test result?

PMID- 11287769
TI  - Posterior leukoencephalopathy syndrome during steroid therapy in a down syndrome
      patient with nephrotic syndrome.

PMID- 11287770
TI  - Surgical correction of nephrotic syndrome.

PMID- 11287771
TI  - Linear growth of low-dose cyclosporin A therapy in children with steroid
      dependent nephrotic syndrome.

PMID- 11287772
TI  - Advanced glycation end products in end-stage renal disease and their removal.

PMID- 11287773
TI  - Plasticity of intercalated cell polarity: effect of metabolic acidosis.
AB  - The cortical collecting duct (CCD) is capable of secreting H(+) or HCO3(-)
      depending on the acid-base status in vivo. Transport is a function of two types
      of intercalated cells in the CCD: A-intercalated cells secrete H(+) and B
      intercalated cells secrete HCO3(-). Metabolic acidosis results in a decrease in
      HCO3(-) secretion and an increase in H(+) secretion by the respective cells.
      Using a model of metabolic acidosis in vitro, we have shown that the down
      regulation of HCO3(-) secretion occurs by endocytosis of apical anion exchangers
      in B-intercalated cells. The finding of basolateral anion exchangers in some
      adapted B-intercalated cells is consistent with a reversal of functional
      epithelial polarity. Plasticity of polarity is also observed in cultured
      intercalated cells: high-density plating results in converting B- to A
      intercalated cells via the deposition of the novel protein hensin in the
      extracellular matrix. A key problem in renal physiology is to investigate the
      role of hensin in mediating the adaptation of the CCD to acidosis in vitro and in
      vivo.

PMID- 11287774
TI  - Upregulation of fractalkine in human crescentic glomerulonephritis.
AB  - BACKGROUND/AIM: To evaluate the importance of fractalkine, a novel member of the
      CX3C chemokine, and natural killer (NK) cells in human crescentic
      glomerulonephritis, we determined the presence of fractalkine in the diseased
      kidneys immunohistochemically, and the correlation among fractalkine, NK cells
      and the degree of renal damage. METHODS: Twenty-three patients (13 males and 10
      females) with primary or secondary crescentic glomerular disease were evaluated
      in this study. Fractalkine and CD16-positive cells including NK cells were
      detected immunohistochemically. RESULTS: Fractalkine-positive cells were detected
      in the interstitium of 23 patients with crescentic glomerulonephritis, while they
      were not detected in the glomeruli. In addition, CD16-positive cells were
      detected in both the glomeruli (1.3 +/- 0.2/glomerulus) and interstitium (1.3 +/-
      0.2/visual field). The number of fractalkine-positive cells in the interstitium
      correlated with the number of CD16-positive cells before glucocorticoid therapy
      (r = 0.43, p = 0.047, n = 23). The number of fractalkine-positive cells in the
      interstitium before glucocorticoid therapy (0.2 +/- 0.1/visual field) decreased
      after therapy (0.1 +/- 0.1/visual field, p = 0.050) in 11 cases tested. The
      number of CD16-positive cells in the diseased kidneys did not change after
      glucocorticoid therapy. CONCLUSION: These results suggest that the local
      production of fractalkine may explain the presence of CD16-positive cells
      including NK cells, which may participate in the interstitial lesions of human
      crescentic glomerulonephritis before corticoid therapy.

PMID- 11287775
TI  - Urinary prostaglandin D synthase (beta-trace) excretion increases in the early
      stage of diabetes mellitus.
AB  - OBJECTIVE: Circulating levels of lipocalin-type prostaglandin D synthase (L
      PGDS)/beta-trace reportedly increase in renal failure as well as in
      cardiovascular injuries. We investigated the alterations of L-PGDS in urine and
      plasma in the early stage of type-2 diabetic patients. METHOD: Thirty-six type-2
      diabetic patients and 29 normal subjects were studied. Overnight spot urine and
      plasma samples were obtained in the morning. L-PGDS was measured by ELISA method
      using anti-L-PGDS antibody. Variables indicating renal function were determined.
      RESULTS: Plasma L-PGDS concentration was slightly higher in the patients with
      diabetes mellitus than in the control subjects, whereas the urinary L-PGDS
      excretion almost doubled in the diabetic patients as compared with that in the
      control subjects. Plasma L-PGDS was determined by plasma creatinine (Cr)
      concentration while urinary L-PGDS excretion was correlated solely with urinary
      protein excretion. There was no relationship between plasma L-PGDS concentration
      and urinary L-PGDS excretion. The averaged plasma concentration of L-PGDS in the
      diabetics with a normal Cr level in plasma, corresponding to that in the
      controls, was determined by the plasma Cr concentration. On the other hand, the
      urinary L-PGDS excretion was determined by the amount of proteinuria and greater
      in the diabetics with a normal Cr level in plasma than in the controls even when
      the patients exhibited urinary protein excretion equal to that in the control
      subjects. CONCLUSIONS: Urinary L-PGDS excretion increased in the early stage of
      kidney injury in patients with type-2 diabetes mellitus. The urinary excretion
      was correlated independently with urinary protein excretion even when there was
      no difference in urinary protein or albumin excretions, thereby suggesting that
      urinary L-PGDS excretion is possibly a more sensitive indicator of renal injuries
      than proteinuria. Urinary L-PGDS may thus predict the progression of renal
      injuries in diabetic patients.

PMID- 11287777
TI  - Serum uric acid and renal prognosis in patients with IgA nephropathy.
AB  - BACKGROUND/AIMS: This study was designed to elucidate the clinical significance
      of serum uric acid (SUA) and the relationship between hyperuricemia and renal
      prognosis in IgA nephropathy. METHODS: The correlation between SUA and other
      clinical parameters were examined in 748 IgA nephropathy patients (432 males and
      316 females). Among these patients, 226 (144 males and 82 females) who were
      followed for more than 5 years were examined for the relationship between
      hyperuricemia and renal prognosis. RESULTS: In IgA nephropathy, SUA correlated
      negatively with creatinine clearance (Ccr), and positively with urinary protein
      and tubulointerstitial damage. SUA was higher in patients with hypertension or
      diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for
      renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p =
      0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after
      more than 8 years was -22.3 +/- 20.8% in 13 patients with hyperuricemia, compared
      with +2.6 +/- 39.4% in 43 patients without hyperuricemia (p = 0.0238).
      Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461).
      CONCLUSION: Hyperuricemia in IgA nephropathy is derived from both glomerular and
      tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a
      risk factor for renal prognosis in IgA nephropathy.

PMID- 11287776
TI  - Vitamin B(6) therapy does not improve hematocrit in hemodialysis patients
      supplemented with iron and erythropoietin.
AB  - BACKGROUND/AIM: Pyridoxine deficiency may be the cause of failure to respond
      appropriately to iron and erythropoietin (EPO) administration in hemodialysis
      patients. METHOD: We studied 36 patients on chronic hemodialysis amply
      supplemented with iron and EPO, who failed to raise hematocrit levels >33%.
      Patients were divided into three equal groups and evaluated for 6 months as
      follows: Group A -- no additional therapy; group B -- supplemented with oral
      pyridoxine 50 mg/day, and group C received 100 mg/day pyridoxine orally. RESULTS:
      In all our patients, erythrocyte pyridoxine levels were initially within
      reference range for a healthy population and did not vary significantly during
      the study period. Likewise, ferritin levels and iron saturation values remained
      normal and constant. Hemoglobin and/or hematocrit levels remained practically
      unchanged in all three groups. CONCLUSIONS: The results indicate that in
      hemodialysis patients with normal pyridoxine status who, despite appropriate
      supplementation of iron and EPO, fail to reach optimal hematocrit levels,
      additional pyridoxine treatment does not produce any hematocrit elevation.

PMID- 11287778
TI  - Inheritance of a stable mutation in a family with early-onset disease.
AB  - Autosomal/dominant polycystic kidney disease (ADPKD) exhibits a high inter- and
      intrafamilial heterogeneity partly explained by the involvement of at least 3
      different genes in the disorder transmission. PKD1, the major locus, is located
      on chromosome 16p. The occurrence of very early-onset cases of ADPKD (sometimes
      in utero) in a few PKD1 families or the increased severity of the disease in
      successive generations raise the question of anticipation. This is a subject of
      controversial discussion. This report deals with the molecular analysis in
      families with very early-onset ADPKD. The finding of the same stable mutation
      with such different phenotypes rules out a dynamic mutation. The molecular basis
      of severe childhood PKD in typical ADPKD families remains unclear; it may include
      segregation of modifying genes or unidentified factors and the two-hit mechanism.

PMID- 11287779
TI  - Effect of high glucose concentration on the synthesis of monocyte chemoattractant
      protein-1 in human peritoneal mesothelial cells: involvement of protein kinase C.
AB  - Human peritoneal mesothelial cells (HMC) contribute to the activation and control
      of inflammatory processes in the peritoneum by their potential to produce various
      inflammatory mediators. The present study was designed to assess the effect of
      glucose, the osmotic active compound in most commercially available peritoneal
      dialysis fluids, on the synthesis of the C-C chemokine monocyte chemoattractant
      protein-1 (MCP-1) in cultured HMC. The MCP-1 concentration in the cell
      supernatants was determined by enzyme-linked immunosorbent assay and the MCP-1
      mRNA expression was examined using Northern blot analysis. Incubation of HMC with
      glucose (30-120 mM) resulted in a time- and concentration-dependent increase in
      MCP-1 protein secretion and mRNA expression. After 24 h the MCP-1 synthesis was
      increased from 2.8 +/- 0.46 to 4.2 +/- 0.32 ng/10(5) cells (n = 5, p < 0.05) in
      HMC treated with 60 mM glucose. In contrast, osmotic control media containing
      either the metabolically inert monosaccharide mannitol or NaCl did not influence
      MCP-1 production. The stimulating effect of high glucose on MCP-1 expression in
      HMC was mimicked by activation of protein kinase C (PKC) with the phorbol ester
      PMA (20 nM). Coincubation of the cells with glucose and the specific PKC
      inhibitor Ro 31-8220 completely blunted glucose-mediated MCP-1 expression. In
      summary, our results indicate that glucose induces MCP-1 synthesis by a PKC
      dependent pathway. Since osmotic control media did not increase MCP-1 release, it
      is suggested that the effect of glucose is mainly related to metabolism and not
      to hyperosmolarity. These data may in part explain elevated steady-state levels
      of MCP-1 found in the dialysis effluent of continuous ambulatory peritoneal
      dialysis patients.

PMID- 11287780
TI  - Sialyl Lewis X and anti-P-selectin antibody attenuate lipopolysaccharide-induced
      acute renal failure in rabbits.
AB  - BACKGROUND/AIM: Acute renal failure (ARF) is one of the common problems
      associated with sepsis or multiple organ dysfunction syndrome (MODS). We have
      investigated the effects of inhibiting selectin-mediated cell adhesion on
      lipopolysaccharide-induced ARF in rabbits, using sialyl Lewis X oligosaccharide
      and PB1.3, an anti-human P-selectin monoclonal antibody, as inhibitors. METHODS:
      ARF was induced by intravenous administration of lipopolysaccharide (0.3 mg/kg,
      i.v. bolus injection) to New Zealand White rabbits. Induction of ARF was
      characterized by increases in blood urea nitrogen (BUN), creatinine, and the
      number of polymorphonuclear leukocytes infiltrating glomeruli, and by fibrin
      deposition in glomeruli, and tubular dilatation in the kidney. Sialyl Lewis X
      oligosaccharide (14 mg/kg, i.v. bolus injection immediately before
      lipopolysaccharide administration and 9 mg/kg/h, i.v. infusion) or PB1.3 (5
      mg/kg, i.v. bolus injection before lipopolysaccharide administration), anti-P
      selectin antibody, were treated. RESULTS: Treatment with sialyl Lewis X
      oligosaccharide inhibited the increases in BUN, creatinine, and the number of
      infiltrating polymorphonuclear leukocytes, and attenuated histopathological
      impairments. Similarly, treatment with PB1.3 prevented some of the
      characteristics associated with lipopolysaccharide-induced ARF, not but the
      increase in creatinine. CONCLUSION: These results suggest that selectin
      inhibitors, including sialyl Lewis X oligosaccharide and PB1.3, may provide
      clinical benefits in the prevention of ARF associated with sepsis and MODS. To
      our knowledge, this is the first report that P-selectin is directly involved in
      lipopolysaccharide-induced ARF in rabbits.

PMID- 11287782
TI  - De novo fibrillary glomerulopathy in the renal allograft of a patient with
      systemic lupus erythematosus.
AB  - Lupus glomerulonephritis is a complication of systemic lupus erythematosus, with
      10% of the patients developing end-stage renal disease. It is accepted that lupus
      patients are good candidates for kidney transplantation and that the disease
      activity is subdued after transplantation due to rigorous immunosuppression, with
      a low rate of graft loss due to recurrent glomerulonephritis. While recurrent
      fibrillary glomerulopathy has been reported in renal allografts, de novo disease
      has not. We report a patient with systemic lupus who underwent a renal
      transplantation and subsequently lost her allograft due to de novo fibrillary
      glomerulopathy. Four years after her first kidney transplant, the patient
      presented with acute deterioration of her renal function. A renal biopsy was
      performed, and it revealed a focal mesangioproliferative pattern with positive
      amorphous mesangial immunofluorescence staining for IgG and C3. Congo red
      staining was negative. Electron microscopy demonstrated the presence of randomly
      oriented nonamyloid fibrils in the mesangiun. The diagnosis of de novo fibrillary
      glomerulopathy was made. The patient lost her allograft and received a second
      cadaveric renal transplant 1 year later. She has had a stable renal function
      since then.

PMID- 11287781
TI  - Cyclosporine-associated thrombotic microangiopathy during daclizumab induction: a
      suggested therapeutic approach.
AB  - A woman on daclizumab developed thrombotic microangiopathy secondary to
      cyclosporine after a living-unrelated kidney transplant. Despite cyclosporine
      discontinuation, hemolysis persisted. The second dose of daclizumab was postponed
      24 h, and after a maximum of two sessions of plasmapheresis (to avoid further
      modifications in daclizumab schedule) with plasma exchange, daclizumab was
      administered. Plasma infusions were prescribed until D-dimer and fibrinogen
      degradation products normalized; thereafter, FK-506 was started without
      recurrence of the hemolytic picture and renal function restored. This observation
      suggests that in patients on daclizumab who develop thrombotic microangiopathy
      secondary to immunosuppressants, if discontinuation of the offending drug is
      unsuccessful, plasmapheresis with plasma exchange can be performed when the
      lowest levels of daclizumab exist, followed by daclizumab infusion. Plasma
      prescription must be continued thereafter until D-dimer and figrinogen
      degradation products normalize. However, if hemolysis persists when daclizumab
      levels are high, plasma infusions are useful and plasmapheresis avoided. FK-506
      administration did not result in recurrence of hemolysis during daclizumab
      induction.

PMID- 11287783
TI  - Urinary von Willebrand factor as a marker of lupus nephritis progression.

PMID- 11287784
TI  - Corticosteroids in cholesterol emboli syndrome.

PMID- 11287785
TI  - Mannose-binding lectin contributes to glomerulonephritis induced by hepatitis C
      virus infection.

PMID- 11287786
TI  - Serotonin 6 receptor polymorphism in schizophrenia: frequency, age at onset and
      cognitive function.
AB  - The relative abundance of serotonin 6 receptor (5HT6) in some limbic regions and
      the high affinity of some antipsychotics for 5HT6 suggest that the 5HT6 gene
      might play a role in the pathogenesis of schizophrenic disorders. A recent study
      reported an association between a C267T polymorphism of the 5HT6 gene and
      schizophrenia. In order to test whether the 5HT6 gene plays a role in the
      pathogenesis of schizophrenic disorders, patients (n = 148) and control subjects
      (n = 160) were genotyped for 5HT6. We also investigated the relationship between
      genotypes and patients' age at onset and cognitive function in schizophrenic
      patients. Cognitive function in the patients was evaluated by the Mini-Mental
      State Examination (MMSE). The results demonstrated no significant differences in
      genotype or allele frequencies between controls and patients. In the patient
      group, age at onset and MMSE score did not differ significantly among the three
      5HT6 genotpyes. The results of this study suggest that the 5HT6 C267T
      polymorphism plays no major role in susceptibility to the development of
      schizophrenia and is not related to cognitive impairment or age at onset in
      schizophrenic patients. Further studies of the relation between 5HT6 polymorphism
      and the symptoms and the therapeutic response in schizophrenic patients may help
      to elucidate the role of 5HT6 in the pathogenesis of schizophrenia.

PMID- 11287787
TI  - No correlation between aggression and platelet (3)H-paroxetine binding in
      obsessive-compulsive disorder patients.
AB  - Different findings suggest that the serotonin (5-HT) system may be involved in
      both the regulation of aggression and the pathophysiology of obsessive-compulsive
      disorder (OCD). Our study aimed to evaluate the aggressive features of a group of
      OCD patients and to explore possible correlations with a serotonergic marker,
      namely platelet 5-HT transporter. Psychopathological and biological patterns were
      compared with those of a group of healthy controls and those of patients with
      major depression. Twenty-one patients affected by OCD, 21 by depression and 21
      healthy controls were included in the study. Aggressive features were measured by
      means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT
      transporter was evaluated by means of the (3)H-paroxetine binding parameters
      (maximum binding capacity, B(max) and dissociation constant, K(d)). The OCD
      patients showed a total score on the BDHI not significantly different from that
      of healthy controls and lower than that of depressed patients. The factor profile
      was similar in the 3 groups, but higher in the depressed patients. The
      irritability, resentment, guilt, negativism and suspiciousness factors were
      significantly more pronounced in depressed patients. Some sex-related difference
      in single factors were also observed. The B(max) of (3)H-paroxetine binding was
      lower in OCD patients than in depressives or healthy controls. OCD patients were
      more similar to healthy controls than to depressed patients with regard to
      aggressive features measured by means of the BDHI. This suggests that aggression
      in OCD is a complex phenomenon that probably requires specific instruments of
      evaluation.

PMID- 11287788
TI  - mRNA expression of serotonin receptors of type 2C and 5A in human resting
      lymphocytes.
AB  - We investigated the presence of mRNA for serotonin receptors of type 2C (5
      HT(2C)) in resting lymphocytes by means of RT-PCR and Southern blotting analyses,
      given their possible role in the pathophysiology of anxiety and eating disorders.
      At the same time, we explored also the presence of the specific mRNA for 5-HT(5A)
      receptors, a novel subtype for which still no functional data exist. Healthy
      subjects and patients with obsessive-compulsive or bipolar disorders were
      included in the study. The results showed the presence of the specific mRNAs for
      both 5-HT(2C) and 5-HT(5A) receptors in resting lymphocytes of the three groups
      of subjects. An additional band was also observed after the amplification of the
      5-HT(5A) cDNA in each sample. These findings, while revealing the presence of 5
      HT(2C) and 5-HT(5A) receptor mRNAs in an easily available tissue, can be
      considered preliminary for future quantitative analyses in patients with
      different psychiatric conditions.

PMID- 11287789
TI  - Antidepressive response to sleep deprivation in unipolar depression is not
      associated with dopamine D3 receptor genotype.
AB  - The psychostimulant theory of antidepressive sleep deprivation (SD) proposes a
      contribution of dopamine D3 receptors (DRD3) in the limbic system to the
      antidepressant effects of SD. Neuroendocrinological studies suggest a positive
      correlation of clinical response to SD and cortisol secretion. We hypothesized
      that the clinical response to SD and amount of cortisol secretion upon SD is
      associated with the 1-1 genotype of the Bal1 polymorphism of DRD3 on exon 1. In
      this study, aiming at evaluating the feasibility of screening large patient
      samples, 52 inpatients (19 males/33 females) with unipolar depression and a score
      of 18 or more on the 21-item Hamilton Depression Rating Scale were treated with 1
      night of total SD. We found that 31% of our patients responded to SD. There was
      no association between response to SD and the genotype of the DRD3 Bal1
      polymorphism (p < 0.879). There was also no association between increase in
      cortisol secretion after SD and DRD3 genotypes (p < 1.000) in a subgroup of
      patients. Statistical power analysis ruled out a major effect of the DRD3 Bal1
      polymorphism on clinical response to SD. These results suggest that the DRD3 Bal1
      polymorphism is not a promising lead to be followed up in larger patient samples.

PMID- 11287790
TI  - Polymorphism of the 5'-upstream region of the human SNAP-25 gene: an association
      analysis with schizophrenia.
AB  - Recent studies have suggested that synaptic abnormalities may be part of the
      pathophysiology of schizophrenia. SNAP-25 (synaptosomal-associated protein of 25
      kD) is one of the synaptic proteins responsible for presynaptic
      neurotransmission, axonal elongation and synaptogenesis. Genetic variation in the
      5'-upstream region of the SNAP-25 gene was analyzed in 87 unrelated schizophrenic
      patients and 100 healthy controls. A novel polymorphic (TAAA)(n) tandem repeat
      was identified in the 5'-upstream region. There were no significant differences
      between the patient and the control groups in the distribution of repeat numbers
      of alleles or genotypes. In addition, no associations were found between the
      polymorphism for subtypes, longitudinal courses or positive family history of the
      patients. Our results suggest that polymorphisms in the 5'-upstream region of the
      SNAP-25 gene have no association with schizophrenia.

PMID- 11287792
TI  - Association between GABA-A receptor alpha 5 subunit gene locus and schizophrenia
      of a later age of onset.
AB  - Heritability is considered to be a major etiologic factor for schizophrenia.
      Among the genes considered as candidates for the disease, are those related to
      GABAergic neurotransmission. Our aim was to test for a genetic association
      between GABA-A receptor alpha 5 subunit gene locus (GABRA(5)) and schizophrenia.
      Genotyping of the GABRA(5) locus was performed by the use of a dinucleotide (CA)
      repeat marker in 46 schizophrenic patients and 50 healthy individuals, all
      unrelated Greeks. Eight alleles were identified, 276-290 bp long. A
      nonsignificant excess of the 282-bp allele, which was found in a previous study
      in a Greek population to be associated with bipolar affective disorder, was
      observed in schizophrenic patients (33.8 vs. 23.9% in the controls). The
      frequency of this allele was 43.3% among patients with a later age of onset (over
      25 years), differing at a statistically significant level from the controls (p <
      0.05). These results suggest that common pathophysiological mechanisms may
      possibly underlie affective disorders and schizophrenia, at least in a subgroup
      of patients.

PMID- 11287791
TI  - Dehydroepiandrosterone sulphate and corticotropin levels are high in young male
      patients with conduct disorder: comparisons for growth factors, thyroid and
      gonadal hormones.
AB  - Childhood conduct disorder (CD) may originate in a stressful upbringing, and be
      associated with unusual physical or sexual development and thyroid dysfunction.
      We therefore explored circulating levels of hormones from adrenal, gonadal and
      growth hormone axes associated with stress, aggression and development in 28 CD
      patients and 13 age-matched healthy children (10-18 years old). The CD group had
      higher levels of dehydroepiandrosterone sulphate (DHEA-S), corticotropin (ACTH)
      and free tri-iodothyronine (fT(3)) if under 14 years. There were no differences
      for gonadal hormones or maturity ratings which were not associated with
      aggression. Smaller physical measures in CD children correlated with DHEA-S and
      growth factors (e.g. insulin-like growth factor I) increased ACTH and fT(3)
      correlated with restless-impulsive ratings, and DHEA-S with 'disruptive
      behaviour'. Imbalances in the adrenal and growth axes may have neurotropic
      repercussions in development.

PMID- 11287793
TI  - Serum contents of the free forms of alpha(1)-microglobulin and ulinastatin:
      relation to diseased states in patients with mood disorders.
AB  - We have found previously that the relationship between the urinary contents of
      alpha(1)-microglobulin (alpha(1)M) and ulinastatin (UT) in patients with mood
      disorder differs from that of age-matched healthy subjects. However, it has yet
      to be determined whether or not the difference in the relation correlates with
      the contents of the free forms of alpha(1)M and UT in serum and whether changes
      in the existing forms of alpha(1)M and UT in serum reflect the actual disease
      states. The relation between serum contents of the free forms of alpha(1)M and UT
      in 10 patients with mood disorders was different from that of 17 age-matched
      healthy subjects. The regression plot between scores of the Hamilton Rating Scale
      for Depression and ratios of the free form content to total content (F/T ratio)
      of UT was more informative on the depressive state than that of alpha(1)M. The
      F/T ratios of UT may afford a useful objective index in monitoring the diseased
      state of a patient with mood disorder.

PMID- 11287794
TI  - Posttraumatic stress disorder: diagnosis and epidemiology, comorbidity and social
      consequences, biology and treatment.
AB  - Epidemiological studies clearly indicate that posttraumatic stress disorder
      (PTSD) is becoming a major health concern worldwide even if still poorly
      recognized and not well treated. PTSD commonly co-occurs with other psychiatric
      disorders, and several symptoms overlap with major depressive disorders, anxiety
      disorders and substance abuse; this may contribute to diagnostic confusion and
      underdiagnosis. This anxiety disorder provokes significant occupational,
      psychiatric, medical and psychosocial disability, and its consequences are
      enormously costly, not only to the survivors and their families, but also to the
      health care system and society. Work impairment associated with PTSD is very
      similar to the amount of work impairment associated with major depression. The
      pathophysiology of PTSD is multifactorial and involves dysregulation of the
      serotonergic as well as the noradrenergic system. A rational therapeutic approach
      should normalize the specific psychobiological alterations associated with PTSD.
      This can be achieved through the use of antidepressant drugs, mainly of those
      that potentiate serotonergic mechanisms. Recent double-blind placebo-controlled
      studies report the efficacy of selective serotonin reuptake inhibitors. Several
      cognitive-behavioral and psychosocial treatments have also been reported to be
      efficacious and could be considered when treating PTSD patients.

PMID- 11287795
TI  - Neurodevelopmental schizophrenia: obstetric complications, birth weight,
      premorbid social withdrawal and learning disabilities.
AB  - Neurodevelopmental schizophrenia seems to be caused by impaired cerebral
      development and is supposed to be associated with obstetric complications (OCs),
      poor premorbid adjustment, schizotypal or schizoid personality traits and
      negative symptoms. In the present study, 36 schizophrenic and schizoaffective
      patients and their same-sex, healthy siblings were recruited. They were diagnosed
      according to DSM-III-R, using structured psychiatric interviews and a consensus
      of 2 psychiatrists. Information on OCs, birth weight, premorbid social and
      learning functioning was obtained from their mothers. The main results show
      significant differences in OCs, birth weight, premorbid social and learning
      functioning between patients and their same-sex, healthy siblings. Using
      multivariate analyses, both premorbid variables were again identified to
      discriminate well between affected and unaffected siblings. Our findings seem to
      confirm the concept of schizophrenia as a neurodevelopmental process.

PMID- 11287796
TI  - First experiences in combination therapy using olanzapine with SSRIs (citalopram,
      paroxetine) in delusional depression.
AB  - In an open prospective study, 26 patients with delusional depression (mood
      congruent psychotic features: DSM-IV 296.4) were treated over 5 weeks with a
      combination of SSRI (citalopram, n = 22, or paroxetine, n = 4) and the
      neuroleptic olanzapine. The course of therapy was evaluated with the Hamilton
      depression scale (HAMD). Not only the total HAMD score, but also the subscores
      for affectivity and delusional symptoms decreased significantly. After the end of
      the 5-week combination therapy, 18 out of 26 patients (69%) could be discharged
      as responders to outpatient treatment. The course of treatment was characterized
      by excellent tolerance.

PMID- 11287797
TI  - Subjective ratings of pain correlate with subcortical-limbic blood flow: an fMRI
      study.
AB  - Studies investigating the cerebral representations of pain using functional
      imaging techniques failed to elucidate the affective aspects of pain. This
      investigation used functional magnetic resonance imaging to measure pain-related
      changes in cerebral activity during painful stimulation with a strong affective
      component. Vascular pain was induced via balloon dilatation of a dorsal foot vein
      of healthy volunteers. The subjects rated their perceived pain uninterruptedly
      during imaging, allowing cerebral activity to be correlated with both stimulus
      function (boxcar) and, more importantly, subjective ratings reflecting individual
      pain experience. The findings indicated signal increases in subcortical-limbic
      regions, particularly in the amygdala. This region is suggested to be involved in
      the affective dimension of pain.

PMID- 11287798
TI  - Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents:
      possible association but no influence of personality disorders.
AB  - OBJECTIVE: Impulsive behavior in alcoholics puts them at serious risk of severer
      course of disease and has been related to the serotonergic neurotransmission
      dysfunction. The aim of this study is to investigate the association between
      impulsive aggression in alcohol dependents with regard to the G-1438A
      polymorphism in the promoter region of the 5-HT2A receptor gene. Furthermore, we
      investigated the statistical interaction between 5-HT2A alleles, antisocial
      personality disorder (APD) and impulsive aggression in alcohol dependents.
      Alcohol dependents were investigated because these personality disorders and
      impulsive behavior are very frequent in alcohol dependence anf of clinical
      relevance. METHODS: One hundred and thirty-five patients of German descent
      meeting DSM-IV criteria of alcohol dependence were recruited. Blood samples were
      taken from alcohol dependents to determine 5-HT2A promoter polymorphisms using
      PCR (polymerase chain reaction) of lymphocyte DNA. Impulsive aggression was
      assessed using a German version of the Barratt Impulsiveness Scale which was
      translated and backtranslated. Alcohol dependents were subdivided into low- or
      high-impulsivity groups using a median split of the Barratt score. APD and
      borderline personality disorder (BPD) were assessed using the SCID-II interview.
      RESULTS: The low-impulsivity group was slightly older and showed a later age at
      alcoholism onset than the highly impulsive group. Alcohol dependents with high
      impulsive traits showed a significant association with 5-HT2A 1438 A alleles.
      After excluding alcohol dependents with APD or BPD from the analysis, this
      association remained significant. Furthermore, no association between APD, BPD
      and 5-HT2A alleles was noted. CONCLUSIONS: Inpatient alcohol dependents showed a
      significant association between 5-HT2A A alleles and impulsive traits,
      independent of the presence of APD or BPD. No association was noted between
      personality disorders and the polymorphism. This is the first report about an
      association of 5-HT2A promoter polymorphism and impulsive behavior in alcohol
      dependents. This finding may refer only to impulsive traits and may be
      independent of personality disorders in this sample. These results have to be
      confirmed in larger samples and in healthy control subjects to determine whether
      this association is of general validity.

PMID- 11287800
TI  - A possible role of apolipoprotein E polymorphism in predisposition to higher
      education.
AB  - A potential candidate gene that could contribute to the education process is the
      apolipoprotein E (apo E) gene that has been shown to correlate with memory
      function and memory decline. We measured apo E polymorphism in groups of probands
      with different levels of education selected from a population sample. In the
      group of probands with higher education (n = 82), 24.4% had the e4 allele,
      compared with 7.3% who had the e2 allele. A reverse association was found in the
      group that left school aged 15 (n = 36) - 8.3% had the e4 allele and 13.9% had
      the e2 allele. Eighty-seven percent of the probands with the allele e4 reached
      higher education, compared to only 54.5% with the allele e2. The difference
      between the groups is statistically significant (p = 0.039), and this may
      indicate some role for the apo E polymorphism in subjects' intelligence or
      ability to learn.

PMID- 11287799
TI  - Dopaminergic lateralisation in the forebrain: relations to behavioural
      asymmetries and anxiety in male Wistar rats.
AB  - Neurochemical lateralisation has been demonstrated in dopaminergic systems in the
      rat brain, and it has been suggested that such lateralisation might contribute to
      asymmetric and emotional behaviour. Here, we investigated dopaminergic brain
      lateralisation in relation to spontaneous and drug-induced behavioural
      asymmetries, and to emotional behaviour in a sample of 24 male Wistar rats.
      Asymmetric behaviour was measured in the open field in the undrugged state and
      after a systemic challenge with the muscarinic receptor antagonist scopolamine
      (0.5 mg/kg). Emotional behaviour was measured in the elevated plus-maze.
      Dopaminergic lateralisation was assessed by means of a post-mortem analysis of
      tissue dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) content. We found
      higher DOPAC/DA ratios in the neostriatum, ventral striatum, frontal cortex and
      amygdala of the right hemisphere. In the open field, the complete sample of rats
      did not show a left/right asymmetry in spontaneous behaviour, whereas systemic
      scopolamine induced a left-sided preference in thigmotactic scanning. A
      correlational analysis yielded individual relationships between behaviour and
      post-mortem neurochemistry, since lateralisation of DOPAC/DA ratios in favour of
      the right ventral striatum was related to right-side thigmotaxis. Furthermore, a
      right dopaminergic lateralisation in the frontal cortex was associated with lower
      anxiety. The study indicates that asymmetries in ventral striatal dopamine might
      contribute to side preferences in thigmotactic scanning while frontal
      dopaminergic lateralisation might influence emotional processing.

PMID- 11287801
TI  - Multimodal electroneurophysiological studies of systemic lupus erythematosus.
AB  - The purpose of this study was to obtain electrophysiological documentation of
      possible involvement of central and peripheral nervous system (CNS and PNS) in
      systemic lupus erythematosus (SLE) patients even in the absence of neurological
      manifestations. The study included 30 consecutive patients with SLE and 25 age-
      and sex-matched volunteers as a control group. They were subjected to
      neurological and rheumatological tests and an extensive battery of
      neurophysiological tests, besides Wechsler adult intelligence scale. Overt
      neurological manifestations were observed in 14 patients (46.7%).
      Neurophysiological data revealed that 25 patients (83%) had at least 2 abnormal
      tests; 11 (68.8%) patients of the asymptomatic group and 14 patients (100%) of
      the symptomatic group with no significant differences between them. Seventeen
      patients (56.7%) had evidence of PNS dysfunction either in nerves (46.7%) or
      muscles (10%); 7 of them in the asymptomatic group. Twenty-four patients (80%)
      had evidence of CNS dysfunction. Twenty-two patients (73%) had abnormalities
      recorded on electroencephalography; 9 patients in the asymptomatic group and 13
      patients in the symptomatic group. Eleven patients (37%) had abnormal values of
      P100 of visual evoked potential; 5 patients in the asymptomatic group and 6 in
      the symptomatic group. Eight patients (26.7%) had abnormal latency of wave I of
      brain stem response; 3 of them in the asymptomatic group. Abnormal prolongation
      of the P300 component of event-related potentials was recorded in 2 patients
      (12.5%) of the asymptomatic group, while low IQ was observed in 8 patients of
      each group. Neurophysiological abnormalities are fairly common in SLE patients
      whether symptomatic or asymptomatic. The use of such tests favors a true
      incidence of nervous system involvement, more accurate diagnosis, and may lead to
      better clinical care before the development of debilitating CNS and PNS changes.

PMID- 11287802
TI  - Dexamethasone blocking effects on mu- and delta-opioid-induced seizures involves
      kappa-opioid activity in the rabbit.
AB  - Previous data indicate that intracerebroventricular administration of agonists
      for mu- and delta-opioid receptors induces limbic seizures in rats, but no data
      are reported in rabbits. We found that the mu- and delta-opioid peptides [D
      Ala(2)-N,Me-Phe(4)-Gly(5)-ol]enkephalin (DAMGO), beta-endorphin and deltorphin
      II, induced EEG non-convulsive hippocampal seizures, and changes in hippocampal
      background EEG, physical parameters and overt behaviour after central
      administration. Dexamethasone pre-treatment prevented DAMGO-, deltorphin II- and
      beta-endorphin-induced seizures as well as changes in background EEG, physical
      parameters and overt behaviour induced by mu-opioid agonists. Dexamethasone
      antagonism on opioid action was blocked by pre-treatment with a protein synthesis
      inhibitor, cycloheximide or by the kappa-opioid antagonist nor-binaltorphimine.
      Our data suggest that dexamethasone influences opioid actions at mu- and delta
      receptors via a protein synthesis mechanism involving kappa-opioid receptors.

PMID- 11287803
TI  - Mania resulting from continuous positive airways pressure in a depressed man with
      sleep apnea syndrome.
AB  - The authors report the case of a 50-year-old man, with no previous history of
      bipolar illness, hospitalized with a very severe depression and who was resistant
      to a 7-weeks treatment of venlafaxine and trazodone (the respective daily doses
      were 300 and 50 mg which were stable during the last 4 weeks). A diagnosis of
      sleep apnea syndrome led to the use of the continuous positive airways pressure
      technique (CPAP). A few days after starting CPAP, he presented a mood switch,
      first hypomanic, then mixed. The authors discuss the contribution of the sleep
      apnea syndrome to the appearance and the maintenance of the depressive disorder.

PMID- 11287804
TI  - Dendritic anomalies in a freezing model of microgyria: a parametric study.
AB  - Despite easier recognition of focal developmental cortical anomalies with modern
      morphological and functional imaging techniques, mechanisms leading to refractory
      epilepsy are still poorly understood. Recent experimental studies have shown that
      not only the lesioned cortex, but also the apparently normal adjacent cortex
      undergoes morphological changes and alterations of its neuronal connections. To
      further investigate the modifications of the cortex surrounding a focal
      maldevelopmental lesion, we applied a freezing insult to newborn rat cortex,
      resulting in a focal cortical malformation similar to human microgyria.
      Corticocortical associative neurons were retrogradely labeled in a Golgi-like
      fashion using biotinylated dextran amine combined with NMDA. In addition to
      previously reported alterations, a considerable spine loss was observed in the
      basal dendrites of neurons located in the eulaminated cortex adjacent to the
      lesion. These data demonstrate profound maldevelopmental alterations which are
      not limited to the macroscopically abnormal lesion, but extend at a cellular
      level to the surrounding cortex. The observed alterations may contribute to the
      increased excitability of the cortex harboring a microgyric lesion as well as the
      frequently associated cognitive impairment.

PMID- 11287805
TI  - Asymptomatic intracranial hypertension in disorders of CSF circulation in
      childhood--treated and untreated.
AB  - Twelve patients are described who were found to have asymptomatic intracranial
      hypertension monitored over an extended (6 months to 6 years) period. There were
      three groups: 5 patients with treated hydrocephalus with an apparently
      functioning shunt, 4 patients with untreated hydrocephalus, clinically and
      radiologically nonprogressive, and 3 patients with pseudotumor cerebri, 2 treated
      and 1 untreated. Although the magnitude of the intracranial pressure changes
      varied, all patients had abnormal baseline pressures together with repeated A and
      B waves. In no case was there any clinical manifestation of raised intracranial
      pressure and in all cases ventricular size remained constant over the period of
      evaluation. The clinical and pathophysiological implications of these findings
      are discussed.

PMID- 11287806
TI  - Intraventricular pressure dynamics in ventriculocholecystic shunting: a
      telemetric study.
AB  - Extracranial cerebrospinal fluid shunting is the current mainstay of therapy for
      hydrocephalus. The generally preferred extracranial site for cerebrospinal fluid
      absorption is the peritoneal space; however, the cardiac atrium and the pleura
      are also commonly used. On occasion other CSF recipient sites, such as the
      gallbladder, are used secondarily when the more common absorptive spaces are
      unavailable or unsuitable. The gallbladder, though, exhibits its own pressure
      dynamics in response to physiological stimuli. The effects of gallbladder
      contraction on intraventricular pressure (IVP) in the presence of a
      ventriculocholecystic (VGB) shunt are unknown. We had the opportunity to place a
      VGB shunt in a 4-year-old child who was coupled to a noninvasive telemonitor.
      After a period of acclimation, we examined the IVP dynamics of that shunting
      system both pre- and postprandially. We found that before ingestion of food, the
      gallbladder provides a CSF recipient site similar to that of the peritoneal
      space. However, after ingestion of a meal containing fat, we found that IVP rose
      more than 10 cm water in a stereotypic fashion consistent with postprandial
      gallbladder contraction. The increase in IVP lasted for several hours reaching a
      peak at approximately 75 min postprandially. We conclude that the VGB shunt is a
      viable alternative for extracranial cerebrospinal fluid shunting; however, one
      must be aware of the peculiar dynamics of this shunt in relation to food
      ingestion and the potential for unusually high IVPs.

PMID- 11287807
TI  - Supratentorial ependymoma in children.
AB  - The clinical and pathological characteristics of supratentorial ependymomas (STE)
      in children are not well identified in the literature, because most series deal
      with ependymomas regardless of their location or the age of the patient. As a
      result, the pathological description of the disorder is still debated. We
      therefore reviewed our cases of children operated for STE and compared them with
      cases of infratentorial ependymomas (ITE) to provide a better characterization of
      STE and suggest guidelines for treatment. From 1985 to 1999, we operated 18
      children for STE, almost half of which developed with no connection to the
      ventricular system. Intraoperative bleeding and infiltration of the basal ganglia
      prevented total removal in 4 cases and were the main causes of operative
      mortality and morbidity. The 5-year overall survival and recurrence-free survival
      rates were 54 and 37%, respectively, and were highly affected by the extent of
      resection, but not by histological grade. Because of the high recurrence rate, we
      recommend systematic postoperative irradiation limited to the tumor site for all
      high-grade tumors in older children, and reoperation after subtotal removal and
      for recurrences.

PMID- 11287809
TI  - Intracranial hemorrhage in neonates with unrecognized hemophilia A: a persisting
      problem.
AB  - Hemophilia is a rare disorder, and an uncommon cause of intracranial hemorrhage
      in neonates. We present 2 patients with hemophilia A, who presented with massive
      subdural hemorrhages on day 5 and day 4 postpartum. Both were taken urgently to
      surgery without a diagnosis of hemophilia being established. Neither patient had
      a family history of hemophilia, and both were born following difficult
      deliveries. The activated partial thromboplastin time (APTT) was normal in
      patient No. 1 (subsequent factor VIII level 10%). In patient No. 2, the APTT was
      slightly prolonged, but initially interpreted as being within the normal range
      for age (subsequent factor VII level of < 1%). Patient 1 rebled, required a
      second operation, and had a poor outcome. Patient 2 was given prophylactic fresh
      frozen plasma, and made a good recovery. Factor VIII assay should be performed in
      all term male babies presenting with intracranial hemorrhage. In urgent
      circumstances, prophylactic clotting therapy should be administered during
      surgery to prevent postoperative bleeding in an undiagnosed hemophiliac.

PMID- 11287808
TI  - Prognostic implications for gadolinium enhancement of the meninges in low-grade
      astrocytomas of childhood.
AB  - BACKGROUND: Persistent gadolinium enhancement on MRI of the meninges in some
      children with low-grade astrocytomas (LGA) is a widely recognized phenomenon. The
      relationship of this finding with the clinical course is unclear. METHODS: From a
      consecutive cohort of 282 children with pathologically confirmed LGA we
      identified all patients with asymptomatic gadolinium enhancement of the meninges
      found on surveillance MRI. A nested case-control study was performed, comparing
      patients with meningeal enhancement to controls without enhancement. RESULTS:
      Twenty-one children were identified with meningeal enhancement. The median follow
      up was 5.2 years with enhancement noted for a median of 2.2 years. The 5-year
      overall survival for this cohort was 91.2% (Greenwood SE 8.0%), and the 5-year
      progression-free survival was 20.9% (SE 11.9%). Five patients are now free of
      disease, while 15 continue to have stable disease. The overall and progression
      free survival was not significantly different compared to controls. CONCLUSIONS:
      Gadolinium enhancement of the meninges on MRI may occur in a significant number
      of children with LGA, particularly juvenile pilocytic astrocytoma, but does not
      appear to affect progression-free or overall survival. Change in management based
      on this finding alone is unwarranted.

PMID- 11287810
TI  - Prognostic factors in children with severe diffuse brain injuries: a study of 74
      patients.
AB  - Severe diffuse brain injury in children has a devastating influence on their
      physical and psychological development. This retrospective study was undertaken
      to analyse the factors that influence outcome in children with such injuries. The
      short-term outcomes (Glasgow outcome score) of 74 children (age < or =15 years)
      with severe diffuse brain injury and no focal operable mass lesions on CT scan,
      admitted between 1992 and 1998 at the National Institute of Mental Health and
      Neurosciences were analysed. The prognostic factors analysed were age, gender,
      time after injury to admission, nature of injury, highest post-resuscitation
      Glasgow coma score (GCS), pupillary reaction, horizontal oculocephalic reflex and
      CT scan findings. The following factors were found to be independent predictors
      of poor outcome: GCS 3-5 (p < 0.003), absent verbal response (p < 0.001), motor
      response score of 1-3 (p < 0.001), absent pupillary reaction (p < 0.001), absent
      oculocephalic reflex (p < 0.001) and presence of traumatic subarachnoid
      haemorrhage on CT scan (p < 0.002). These independent variables were then
      subjected to a stepwise logistic regression analysis, and the most important
      variables for predicting outcome were oculocephalic reflex and GCS, which
      together correctly predicted unfavourable outcome with a sensitivity of 79% and a
      specificity of 65%. An early CT scan or a single CT scan did not have any
      prognostic significance.

PMID- 11287811
TI  - Total resection of an intracerebral hemangioendothelioma in an infant. Case
      report and review of the literature.
AB  - Hemangioendotheliomas (HEs) are vasoformative tumors rarely seen in the CNS.
      Histopathological features determining aggressive phenotypes have not been well
      defined. Potential cytogenetic alterations in these tumors have not been
      previously reported. We present a 4-month-old male infant with a temporal lobe
      HE. Fluorescence in situ hybridization and spectral karyotype analysis revealed
      translocation of chromosome 11q23. This case constitutes the first report of a
      gross total resection of an intracerebral HE in the pediatric age group, and of
      potential cytogenetic alterations involved in its pathogenesis. Based on our
      report and review of the literature, we note a discrepancy between
      histopathological criteria of aggressive tumor biology and clinical behavior.
      Further study of chromosomal abnormalities may be helpful in defining factors
      associated with a higher risk of malignant behavior. We conclude that gross total
      resection is currently the best available treatment option for these tumors,
      regardless of histology.

PMID- 11287812
TI  - Stimulatory and protective effects of alkylating agents applied in ultra-low
      concentrations.
AB  - Alkylating drugs belonging to the nitrogen mustard family are known as cytostatic
      and immunosuppressive agents. Ultra-low doses of these drugs may demonstrate
      pharmacological effects unlike this category of drugs. In the case of a gradual
      dose decrease, the number of targets for alkylation is also reduced and the drug
      switches from cytostatic to cell growth modifier. We postulate that application
      of ultra-low doses of alkylating drugs may result in a beneficial effect in the
      therapy of diseases associated with chronic inflammation of the mucosa,
      especially with the signs of epithelial atrophy.

PMID- 11287813
TI  - Adverse effects of intravenous immunoglobulin therapy in 56 patients with
      autoimmune diseases.
AB  - OBJECTIVE: To test the adverse effects and viral safety of intravenous
      immunoglobulin (IVIg) use in autoimmune diseases. METHODS: Fifty-six patients
      with various autoimmune diseases who were treated with one to six IVIg courses
      were evaluated for the presence of adverse effects following IVIg therapy and
      were screened before and after the treatment for the presence of serum human
      immunodeficiency virus antibodies, hepatitis C virus antibodies, and hepatitis B
      surface antigen. RESULTS: Among the 56 patients, 20 (36%) had at least one
      adverse effect following at least one of the treatment courses. These included
      headache, low-grade fever, chills, anemia, low-back pain, transient hypotension,
      nausea, intensified perspiration, and superficial and deep vein thromboses.
      Whereas the presence of adverse effect to IVIg was unrelated to either the
      clinical response to the treatment or to the nature of the autoimmune disease,
      the occurrence of an adverse effect in the first treatment course was
      significantly associated with a greater chance for an adverse effect in the
      subsequent courses. No transmission of any of the three viral agents examined
      could be detected. CONCLUSIONS: Although IVIg use in autoimmune diseases is
      associated with adverse effects in about one third of the patients, these effects
      are usually mild and transient. Patients who develop adverse effects during the
      first treatment course may be at increased risk of adverse effects during the
      subsequent IVIg courses.

PMID- 11287814
TI  - Reinforcing effects of MDMA ("ecstasy") in drug-naive and cocaine-trained rats.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is one of the most prevalent
      illegal drugs of abuse among European adolescents, a population not generally
      experienced with respect to "hard" drugs such as cocaine. We, therefore,
      determined the reinforcing effect of intravenously self-administered MDMA in a
      fixed ratio 1 time-out 150 s schedule of reinforcement in rats that were truly
      drug naive and compared it to cocaine-trained rats. The reinforcing effect of
      MDMA [0.032-10 mg/(kg.injection)] did not differ between drug-naive rats and
      cocaine-trained ones. MDMA sensitized the animals to its own rate-increasing
      effect but not to that of cocaine. When MDMA was tested after cocaine, there was
      no carryover of cocaine's reinforcing effect to that of MDMA, suggesting that
      MDMA and cocaine produce distinct interoceptive stimuli in rats.

PMID- 11287815
TI  - Effects of the calcium release inhibitor dantrolene and the Ca2+-ATPase inhibitor
      thapsigargin on spinal nociception in rats.
AB  - The effects produced by the intrathecal administration of dantrolene and
      thapsigargin, measured in several analgesic tests in the rat are described.
      Dantrolene decreases the release of calcium from intracellular stores and
      thapsigargin is able to inhibit the reticular Ca2+-ATPase, avoiding intracellular
      calcium storage. Dantrolene (30-300 nmol/rat) and thapsigargin (3-30 nmol/rat)
      reduced the nociceptive behavior (biting, scratching, licking; BSL) produced by
      the NK(1) receptor agonist septide (0.5 microg), without affecting the BSL
      induced by AMPA (2 microg) or NMDA (4 microg). Also, both drugs elicited
      analgesia in the tail-flick test but not in the formalin test. The
      antinociceptive effects induced by thapsigargin were more intense and long
      lasting than those produced by dantrolene. These results seem to indicate that
      the intracellular modulation of calcium homeostasis could be an interesting
      target in order to induce spinal analgesia.

PMID- 11287816
TI  - Acute antidepressant-like and antianxiety-like effects of tryptophan in mice.
AB  - The antidepressant-like, antianxiety-like and sedative effects of tryptophan
      (TRP), in the absence and presence of p-chlorophenylalanine (p-CPA), and
      melatonin were studied in mice using the forced-swimming test, open-field test
      and activity cage, respectively. Single-dose TRP caused an antidepressant-like
      effect dose dependently up to 125 mg/kg. No significant effect was observed,
      however, when the TRP dose was increased to 250 mg/kg, i.e. a reversal of effect
      occurred at high dose. With p-CPA pretreatment, the effects observed at 125 and
      250 mg/kg TRP were similar to those obtained at 50 and 125 mg/kg without p-CPA
      pretreatment, respectively. Melatonin also caused an antidepressant-like effect
      in a similar manner, but appeared to be less potent than TRP. These results
      strongly indicate that the antidepressant-like effect of TRP was due to its
      conversion to 5-hydroxytryptamine (5-HT). An antianxiety-like effect was observed
      for TRP only at 250 mg/kg dose together with p-CPA pretreatment, while no
      sedative effect was observed at all. In contrast, melatonin did not produce any
      antianxiety-like effect, but produced sedation at 200 mg/kg dose. It may be
      concluded that the antianxiety-like effect of TRP is unrelated to 5-HT and
      melatonin formation, but associated with TRP itself or, perhaps, with other
      anxiolytic metabolites.

PMID- 11287817
TI  - Central serotonergic mechanisms on head twitch response induced by benzodiazepine
      receptor agonists.
AB  - Intraperitoneal injection of benzodiazepine receptor agonists (estazolam,
      zopiclone, triazolam: 0.03-0.24 mmol/kg) induces the head twitch response (HTR).
      The present study was undertaken to examine the possible participation of the
      serotonergic system in the mechanism of head twitches induced by benzodiazepine
      receptor agonists (BZ-RAs). The HTR induced by BZ-RAs was suppressed by
      pretreatment with ketanserine (1 mg/kg, i.p.), a selective 5-HT(2) receptor
      antagonist. Pretreatment with fluoxetine (10 mg/kg, i.p.), a 5-HT reuptake
      inhibitor, and 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT(1A) receptor
      agonist, also suppressed the HTR induced by BZ-RAs. These results suggest that
      the HTR induced by BZ-RAs may be the result of an activation of postsynaptic 5
      HT(2) receptors, probably due to direct action.

PMID- 11287818
TI  - Encapsulation in cationic liposomes enhances antitumour efficacy and reduces the
      toxicity of etoposide, a topo-isomerase II inhibitor.
AB  - Etoposide exerts its antineoplastic effect by forming a ternary complex with topo
      isomerase II and DNA, leading to DNA breaks and cell death. However, it causes
      myelosuppression and its lipophilicity poses a major limitation during
      administration. Liposomes have been reported to increase the efficacy and reduce
      the toxicity of antineoplastic agents. Recent evidence suggests that cationic
      liposomes bind efficiently to tumours. The present study was thus designed to
      encapsulate etoposide in cationic liposomes and to evaluate its antitumour
      efficacy and systemic toxicity in comparison with a conventional parenteral
      formulation. Etoposide encapsulated in liposomes was synthesised by thin film
      hydration followed by an extrusion method. Fibrosarcoma was induced in mice by
      subcutaneous administration of 20-methylcholanthrene. Chemotherapy was started
      when the tumour reached 200 mm(3) in volume. Liposomal etoposide (10 mg/m(2)/day
      for 5 days) significantly delayed tumour growth as compared to non-liposomal
      etoposide. The median time of death was calculated to be 19.5, 26.25 and 56 days
      in vehicle-treated controls, non-liposomal-etoposide- and liposomal-etoposide
      treated groups, respectively. A transient reduction in body weight was seen in
      both the liposomal- and non-liposomal-etoposide-treated groups. The maximum
      tolerated dose was however significantly higher in the group treated with
      liposomal etoposide, which also exhibited a lesser degree of myelosuppression
      than the animals treated with non-liposomal etoposide. The present findings
      suggest that cationic liposomes could be considered as potential for delivery of
      etoposide to tumours.

PMID- 11287819
TI  - Diabetes-induced changes in retinal NAD-redox status: pharmacological modulation
      and implications for pathogenesis of diabetic retinopathy.
AB  - Diabetes-induced changes in retinal metabolism and function have been linked to
      increased aldose reductase activity, hypoxia or 'pseudohypoxia' (increase in
      NADH/NAD+ attributed to increased sorbitol dehydrogenase activity). To address
      this controversy, we evaluated the effects of two vasoactive compounds, alpha(1)
      adrenoceptor antagonist prazosin and antioxidant DL-alpha-lipoic acid, as well as
      sorbitol dehydrogenase inhibitor (SDI-157) and aldose reductase inhibitor
      (sorbinil) on retinal free mitochondrial and cytosolic NAD+/NADH ratios in
      streptozotocin-diabetic rats. Diabetes-induced decrease in mitochondrial and
      cytosolic NAD+/NADH ratios was completely or partially corrected by prazosin and
      DL-alpha-lipoic acid (despite the fact that prazosin did not affect and DL-alpha
      lipoic acid even further increased sorbitol pathway activity) as well as by
      sorbinil, whereas SDI-157 was totally ineffective. Hypoxia-like metabolic changes
      in the diabetic retina originate from aldose reductase, but not sorbitol
      dehydrogenase activity.

PMID- 11287821
TI  - The effect of lactate on sex differences in rat renal tubular energy-dependent
      transport of the organic cation amantadine.
AB  - The purpose of this study was to determine if the inhibitory effect of lactate on
      the tubular transport of amantadine would extend to a demonstrable sex difference
      between male and female rats. Enriched fractions of renal proximal and distal
      tubules were incubated with [(3)H]-amantadine in the presence and absence of
      racemic lactate. Lactate buffer unmasked a sex difference in proximal tubular
      transport capacity. Compared to bicarbonate, lactate also decreased the affinity
      for amantadine uptake by both proximal and distal tubule fragments in both male
      and female rats. No difference occurred between male and female rats in terms of
      the inhibitory constant (K(i)) for lactate. These data suggest that female rats
      have decreased amantadine transport efficiency and potentially increased
      susceptibility to amantadine toxicity due to transport inhibition by lactate. Our
      data may help to explain the mechanism for increased amantadine toxicity observed
      in elderly female patients.

PMID- 11287820
TI  - Antidiarrheal activity of wood creosote: inhibition of muscle contraction and
      enterotoxin-induced fluid secretion in rabbit small intestine.
AB  - Wood creosote has long been used as an antidiarrheal agent, but its mechanism of
      action is not well understood. To elucidate the mechanism of its antidiarrheal
      activity, we have addressed questions whether it inhibits fluid secretion induced
      by Escherichia coli heat-stable enterotoxin (STa) in rabbit jejunum in vivo, and
      whether it inhibits muscle contraction of isolated rabbit ileum ex vivo. Wood
      creosote (10-100 mg/l) instilled in a ligated loop of jejunum inhibited STa
      induced fluid secretion (p < 0.05). It also inhibited the spontaneous phasic,
      acetylcholine-induced tonic and Ba2+-induced tonic contractions of longitudinal
      and circular muscles of ileum dose-dependently with IC(50) values of 130-530
      mg/l. These data provide further evidence that the antidiarrheal activity of wood
      creosote is attributable to its antisecretory and antimotility effects.

PMID- 11287822
TI  - Pathogenesis and pathology of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by airflow
      limitation. Since flow is the result of a driving pressure that promotes flow and
      of an opposing resistance that contradicts it, the reduction in flow observed in
      COPD has two main components: increased resistance, which is due to airway
      obstruction, and a loss of the elastic recoil pressure of the lung, which is due
      to parenchymal destruction. Although it has long been known that the major site
      of increased resistance in COPD is the peripheral airways, recent studies have
      shown that central airways are involved in the disease as well. The purpose of
      this review is to describe the major structural and cellular changes present in
      peripheral airways, central airways and lung parenchyma of patients with COPD,
      and to underline the possible mechanisms contributing to airflow limitation in
      these subjects.

PMID- 11287823
TI  - Wake up sleepy head: sleep can be dangerous.

PMID- 11287824
TI  - Attenuation of the Hering-Breuer reflex: yet another adverse consequence of COPD?

PMID- 11287825
TI  - Divine design or malevolent fate.

PMID- 11287826
TI  - Mechanisms of endothelin-1 elevation in chronic obstructive pulmonary disease
      patients with nocturnal oxyhemoglobin desaturation.
AB  - BACKGROUND: Nonapneic, oxyhemoglobin desaturation associated with sleep has been
      described in patients with chronic obstructive pulmonary disease (COPD).
      Hypoxemia stimulates endothelin-1 (ET-1) secretion. Once released, ET-1 can act
      locally to elicit sustained pulmonary artery vasoconstriction,
      bronchoconstriction and activation of alveolar macrophages. OBJECTIVE: The aim of
      this study was to examine a possible correlation between ET-1 levels and
      nocturnal, nonapneic, oxyhemoglobin desaturation during sleep, in patients with
      COPD. METHODS: We examined 48 COPD patients with formal polysomnography (EEG,
      ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of
      nocturnal, nonapneic, oxyhemoglobin desaturation. Twelve of them were
      disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of
      them desaturated below a baseline sleep saturation of 90% for 5 min or more,
      reaching a nadir saturation of at least 85%. We collected arterial samples to
      measure ET-1 levels, after 5 min of the first period of desaturation, in each of
      the 19 patients. We also collected arterial samples in the morning, before the
      study, to measure baseline ET-1 levels in all patients. RESULTS: Baseline
      arterial ET-1 levels during the day were very significantly higher in
      'desaturator' COPD patients (2.058 +/- 0.252 pg/ml) compared to 'non-desaturator'
      COPD patients (1.382 +/- 0.159 pg/ml; p < 0.001). Also in 'desaturator' COPD
      patients ET-1, levels during the night were significantly higher (4.297 +/- 1.107
      pg/ml) compared to those during the day (p < or = 0.001) and a significant
      negative correlation was observed between ET-1 levels and degree of desaturation
      (p < 0.0001, r = 0.9305). CONCLUSIONS: According to our study we can conclude
      that (1) ET-1 levels are significantly higher in 'desaturator' COPD patients both
      during the day and during the night, and (2) ET-1 levels correlate negatively
      significant with the degree of the oxyhemoglobin desaturation. These findings are
      consistent with the hypothesis that ET-1 plays a very important role in the
      pathophysiological manifestations of COPD patients.

PMID- 11287827
TI  - Hering-Breuer reflex in normal adults and in patients with chronic obstructive
      pulmonary disease and interstitial fibrosis.
AB  - BACKGROUND: It has been suggested that the Hering-Breuer reflex (HBR) is
      unimportant in adults during normal tidal breathing and that it is elicited only
      if tidal volume is increased above a certain critical threshold. OBJECTIVE: The
      aim of this study was (1) to study the occurrence of the HBR in adults with
      normal pulmonary function and (2) to examine if changes in lung mechanics have
      any effect on the HBR. METHODS: We examined 11 adults with normal pulmonary
      function, 8 patients with chronic destructive pulmonary disease (COPD) and 3 with
      interstitial fibrosis (IF). All subjects were lightly sedated with fentanyl,
      intubated and ventilated with a Servo-900 ventilator. Inspiratory and expiratory
      flow (and after integration, volume) and mouth pressure were recorded from the
      endotracheal tube with a pneumotachograph and a pressure transducer. Pressure
      support ventilation was applied in all patients and functional residual capacity
      (FRC) was measured with the N(2) washout method. Mean (Te(mean)) and maximal
      expiratory time (Te(max)) were determined for each individual for 20 breaths.
      Following several breaths to establish a stable baseline the airway was occluded
      at end inspiration by a shutter. A positive HBR was interpreted as longer Te(occ)
      than Te(max) (Te(occ)/Te(max), %). Occlusion was maintained until negative airway
      pressure occurred and the occlusion time (Te(occ)) was measured. We attempted
      occlusions after the addition of 5 cm H2O positive end-expiratory pressure (PEEP)
      and subsequently with 10, 15 and 20 cm H(2)O PEEP. Te(occ) was measured of
      progressively larger lung volumes. To examine the HBR sensitivity in the three
      groups, we plotted the lung volumes of occlusion against the corresponding
      Te(occ)/Te(max). RESULTS: The ratio Te(occ)/Te(max) increased from 167.5 +/- 82.5
      at normal FRC to 474 +/- 200.2 s (PEEP(20)). On the contrary, in patients with
      COPD, Te(occ)/Te(max) increased from 125.2 +/- 34 to 193.7 +/- 74.2 (p < 0.05).
      CONCLUSIONS: The HBR was positive in all subjects. COPD patients were found to be
      less sensitive to volume changes when compared with normal controls and with IF
      patients.

PMID- 11287828
TI  - Reproducibility of a standardized titration procedure for the initiation of
      continuous positive airway pressure therapy in patients with obstructive sleep
      apnoea.
AB  - BACKGROUND: Manual titration of continuous positive airway pressure (CPAP) under
      polysomnographic control is the method most commonly employed to establish the
      minimal effective pressure (P(eff)) for the treatment of the obstructive sleep
      apnoea syndrome (OSA). To date, however, the reproducibility of P(eff) titrated
      in this way has not been investigated in any detail. OBJECTIVES: The present
      study aims to establish the reproducibility of P(eff) determined by manual
      titrations of CPAP under polysomnographic control in the sleep lab. METHODS: In a
      group of 50 patients (5 women), with a mean (SD) apnoea-hypopnoea index of 39.3
      (21.8), apnoea index of 28.1 (20.9) and oxygen desaturation index of 39.3 (22.6),
      with newly diagnosed OSA, manual titration of CPAP was performed on two
      consecutive nights using the following standard titration protocol: starting at 4
      mbar, CPAP was increased by steps of 1 mbar at intervals of at least 5 min, until
      no signs of airway obstruction could be seen, and arousals were no longer
      elicited. When no airway obstruction was detected over a period of 30 min, the
      pressure was lowered once during the night in steps of 1 mbar at intervals of at
      least 10 min, until obstructive events reappeared, whereupon the pressure was
      again increased as described above, until, once more, no signs of airway
      obstruction and no arousals occurred. The second titration was carried out in a
      blind manner, that is the lab technician did not know the results of the first
      pressure titration. RESULTS: The mean (SD) P(eff) for all titrations was 8.1 mbar
      (2.9). A high level of correlation was found between the P(eff) titrated on the
      first night and that titrated on the second night (Spearman correlation
      coefficient = 0.89). In a few individual cases, however, differences of up to 3
      mbar were found between P(eff) on the first night and P(eff) on the second night.
      On average, the P(eff) measured on the second night was 0.5 mbar (SD = 1.3,
      range: -2.0 to 3.0 mbar) higher than that of the first night. CONCLUSIONS: With
      standardization of the manual titration of CPAP, P(eff) is readily reproducible.
      In individual cases, however, a difference of as much as 3.0 mbar between the two
      titrations is possible.

PMID- 11287829
TI  - Usual interstitial pneumonia: idiopathic pulmonary fibrosis versus collagen
      vascular diseases.
AB  - BACKGROUND: Bronchoalveolar lavage fluid (BALF) lymphocytosis was found in
      patients with usual interstitial pneumonia (UIP) associated with collagen
      vascular diseases (CVD) other than diffuse systemic sclerosis (SSc), but it was
      not found in patients with idiopathic pulmonary fibrosis (IPF), a disease
      histologically diagnosed as UIP. This difference could be partly due to
      variations of UIP spectrums between IPF and interstitial pneumonia associated
      with CVD. METHODS: We scored histopathological findings of lung specimens
      obtained from 31 cases (16 IPF, 9 CVD other than SSc and 6 SSc) using a
      semiquantitative scoring method. All cases were diagnosed as UIP by surgical lung
      biopsy. None of the patients were current smokers. RESULTS: Compared with IPF and
      SSc cases, CVD patients without SSc presented decreased scores of fibrosis (p <
      0.01) and alveolar space cellularity (severity, p < 0.05). Lymphocytes were
      mainly localized in the alveolar walls and the majority of cells in the alveolar
      spaces were macrophages. On the other hand, other scores such as cellularity and
      alveolar wall cell infiltrate did not vary among these three groups. CONCLUSION:
      Fewer macrophages in the alveolar spaces and a decrease in the degree of fibrosis
      may contribute to BALF lymphocytosis more in patients with UIP/CVD non-SSc than
      in patients with IPF/UIP and UIP-SSc.

PMID- 11287830
TI  - A case-controlled study with dornase alfa to evaluate impact on disease
      progression over a 4-year period.
AB  - BACKGROUND: Chronic endobronchial sepsis and profuse airway secretions dominate
      pulmonary disease in cystic fibrosis. Recombinant human DNase I (dornase alfa)
      reduces the viscoelasticity of airway secretions and hence may improve clearance
      of airway secretions. OBJECTIVES: To evaluate the long-term influence of dornase
      alfa on disease progression by performing a case-controlled study with dornase
      alfa over a period of 4 years. METHODS: A cohort of patients with cystic fibrosis
      who have been treated with dornase alfa were matched with a control group of
      patients with cystic fibrosis who had not received treatment with dornase alfa.
      The patients were matched by pulmonary function, age, and then sex. All available
      measurements of forced expiratory volume in one second (FEV1), height, weight and
      sputum bacteriology were collected for periods when the patients were free from
      respiratory exacerbations. RESULTS: Thirty-eight patients were matched. Slopes of
      median changes in FEV1 were -2.19 (-3.32, -1.06) in the control group and -0.75 (
      1.87, 0.36) in the dornase alfa-treated group (p = 0.076). There were more
      infective exacerbations per patient year in the control group [3.13 (1.25-4.25)]
      in comparison to the dornase alfa group [1.25 (0.63-3.0), p = 0.035] over the 4
      year treatment period. Antibiotic requirements were also greater with a median
      43.75 (17.5-60.0) days of intravenous antibiotic use per patient year in the
      control group and 16.25 (8.5-44.0) days in the dornase alfa group (p = 0.034).
      CONCLUSIONS: The trends suggest that dornase alfa may have some influence on
      disease progression but in view of the limitations of the current study the need
      for further long-term studies in larger cohorts of patients is emphasised.

PMID- 11287831
TI  - Iatrogenic pneumothorax: marker gas technique for predicting outcome of manual
      aspiration.
AB  - BACKGROUND: Although manual aspiration is used for treating pneumothorax, the
      post-aspiration radiograph may not be a reliable indicator of whether the pleural
      leak remains. We have previously shown that marker gas can identify an air leak
      in patients with spontaneous pneumothoraces. OBJECTIVE: This study examines
      whether a marker gas technique can be safely used to manage patients with
      iatrogenic pneumothoraces. METHODS: 10 patients with iatrogenic pneumothorax were
      identified among a cohort referred for manual aspiration of pneumothorax, using a
      marker gas technique, in which inspired metered-dose inhaler propellant gas is
      detectable in pneumothorax aspirate using a portable flame ioniser. The presence
      of marker gas was taken to imply a persistent air leak. RESULTS: Marker gas was
      detected in the aspirate from 3 out of 10 pneumothoraces. 2 required intercostal
      tube drainage because of lung collapse following initial aspiration and 1 was
      treated conservatively. Marker gas was not detected in 7 cases (2 post-pacemaker
      insertion, 5 pleural aspiration +/- biopsy), and in all these cases, manual
      aspiration resulted in sustained re-expansion of the lung. There was a trend
      towards a significant relationship between the presence or absence of marker gas
      and the need for a further intervention (p = 0.055). CONCLUSION: The presence or
      absence of a pleural leak during manual aspiration of iatrogenic pneumothorax can
      be demonstrated by this technique. The absence of marker gas in the aspirate
      implies that manual aspiration will be successful, whereas its presence, in most
      cases, predicts either failure of manual aspiration to expand the lung or early
      re-collapse of the lung.

PMID- 11287832
TI  - Human recombinant interferon-alpha2a and interferon-alphaA/D have different
      effects on bleomycin-induced lung injury.
AB  - BACKGROUND: Bleomycin (Bleo)-induced lung injury in mice serves as an animal
      model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains
      unclear, but it comprises both inflammatory and fibrotic components. The cytokine
      interferon (IFN)-alpha is produced by macrophages and may modulate both
      fibrogenesis and the determination of T lymphocyte phenotype in pulmonary
      fibrosis. OBJECTIVE: To investigate the effect of two preparations of recombinant
      IFN-alpha (IFN-alphaA/D and IFN-alpha2a) on Bleo-induced lung injury in C57BL/6
      mice. METHODS: Mice were treated by a single intratracheal (IT) instillation of
      0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN
      alpha preparations, IFN-alphaA/D or IFN-alpha2a in saline, or saline alone were
      administered by daily intraperitoneal injections starting 1 day prior to IT
      instillation. The treatment groups were as follows: IT Bleo and intraperitoneal
      saline; IT Bleo and intraperitoneal IFN-alpha2a; IT Bleo and intraperitoneal IFN
      alphaA/D; IT saline and intraperitoneal IFN-alphaA/D or IFN-alpha2a; IT saline
      and intraperitoneal saline. The animals were sacrificed 14 days after IT
      instillation. Lung injury was evaluated by total and differential cell count in
      bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of
      lung injury and a quantitative image analysis of cellularity and fibrosis
      fraction and by biochemical analysis of lung hydroxyproline content. RESULTS: In
      Bleo-treated mice, IFN-alpha2a treatment caused a significant rise in BAL
      lymphocytes and in cellularity and fibrosis fractions in lung tissue. In
      contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury.
      CONCLUSION: IFN-alpha may enhance Bleo-induced lung injury but this effect varies
      with different IFN preparations.

PMID- 11287833
TI  - Noninvasive method to measure airway obstruction in nonanesthetized allergen
      sensitized and challenged mice.
AB  - BACKGROUND: Conventional methods used to measure bronchoconstriction are
      invasive, technically demanding and time consuming. OBJECTIVES: Our purpose was
      to evaluate a noninvasive method, by barometric whole-body plethysmography (WBP),
      to evaluate bronchoconstriction and bronchial hyperreactivity in mice induced by
      ovalbumin (OA) inhalation challenge in comparison with an invasive method.
      Enhanced pause (P(enh)) was used as an index of airway obstruction. METHODS:
      Eight mice were sensitized by OA (group I) and then challenged with OA. Twenty
      four hours later, pulmonary function testing (PFT) was measured by WBP at
      baseline and after a methacholine (MCh) inhalation challenge. Eight weight
      matched normal mice served as controls (group II). Four hours after PFT in a
      nonanesthetized condition, all animals were anesthetized and paralyzed. Baseline
      PFT was performed by the maximal forced expiratory maneuver (MFEM), and then the
      animals were given varying doses of acetylcholine (ACh; 25, 50, 75, 100
      microg/kg) injected through the jugular vein. Five seconds after ACh injections,
      pulmonary functions were examined, including MFEM, peak airway pressure and total
      lung compliance. After completing PFT, bronchoalveolar lavage (BAL) was
      performed, the animals were sacrificed, and the lungs were examined
      histologically. RESULTS: Group I had increased P(enh) in response to MCh in the
      nonanesthetized condition and decreased flow in the anesthetized condition,
      characterized by greater decreases in MFEM flow rates MFEF 50% and MFEF 25% than
      the control group. The peak flows, MFEF 75%, MFEF 50% and MFEF 25%, for group I
      were lower than those for group II at doses of ACh higher than 25 microg/kg.
      There were concentration-dependent increases in P(enh) in response to aerosolized
      MCh in both groups, but the P(enh) in response to aerosolized MCh was
      significantly enhanced in group I when compared with controls. The doses of MCh
      required for 100% increases in P(enh) were significantly reduced for sensitized
      and challenged mice. There was a positive correlation between provocative doses
      PD200 P(enh) MCh, PD20 MFEF 50% ACh and PD20 MFEF 25% ACh. There was a negative
      correlation between the PD200 P(enh) MCh and the percentage of eosinophils in BAL
      fluid. There was an increased total cell count and an increased percentage and
      absolute number of eosinophils and lymphocytes in the BAL fluid of sensitized
      animals. OA-sensitized mice also had a severe inflammatory reaction of airway and
      lung tissue, characterized by congestion, edema and inflammatory cell
      infiltration and desquamation of bronchial epithelial cells. CONCLUSION: The
      noninvasive method of WBP can be used to evaluate airway obstruction and
      hyperreactivity induced in mice by allergen challenge.

PMID- 11287834
TI  - Role of Na(+)-K(+)-ATPase in sodium nitroprusside-induced relaxation of pulmonary
      artery under hypoxia.
AB  - BACKGROUND: The sodium pump (Na(+)-K(+)-ATPase) plays a part in the regulation of
      smooth muscle contractility, and alterations of enzyme activity by hypoxia could
      contribute to the mechanism of hypoxic pulmonary vasoconstriction. OBJECTIVE: To
      determine the role of Na(+)-K(+)-ATPase in the sodium nitroprusside (SNP)-induced
      relaxation of pulmonary artery in hypoxia. METHODS: Using isolated canine
      pulmonary arterial rings, we measured the relaxant responses of KCI-contracted
      tissues to SNP under hyperoxic (95% O2, 5% O2) and hypoxic conditions (5% O2, 5%
      CO2, 90% N2 in vitro. Na(+)-K(+)-ATPase activity was assessed by measuring
      ouabain-sensitive (86)Rb uptake. RESULTS: The SNP-induced relaxation was reduced
      under hypoxia, so that the maximal relaxation decreased from 80.1 +/- 8.6 to 57.8
      +/- 6.8% (p < 0.01) and the concentration of SNP required to produce 50%
      relaxation increased from 1.9 +/- 0.4 x 10(-6) to 2.6 +/- 0.6 x 10(-5) M (p <
      0.01). Addition of ouabain, an Na(+)-K(+)-ATPase inhibitor, attenuated the
      relaxant response to SNP and this inhibition was still observed under hypoxia.
      Incubation of endothelium-denuded rings with SNP caused dose-dependent increases
      in intracellular cGMP levels and ouabain-sensitive (86)Rb uptake, and these
      effects were not significantly altered by hypoxia. CONCLUSION: These results
      suggest that sarcolemmal Na(+)-K(+)-ATPase activity may be implicated in the
      mechanism of nitrovasodilator-induced vasodilation of pulmonary artery and may
      still be functioning under hypoxia.

PMID- 11287835
TI  - An isoflow-volume technique for assessing airway dynamics in children and adults.
AB  - BACKGROUND: We propose a new approach to the measurement of small airway function
      as an alternative to recordings of maximal expiratory flow-volume (MEFV) curves.
      OBJECTIVES: A newly developed technique to record isoflow-volume (IFV) curves to
      be tested against maximal respiratory flow curves. METHODS: An isoflow whistle
      (IFW; Iflopen) measures the length of a constant expiration after full
      inspiration. The note of the whistle enables a subject to generate an even
      expiration, and the isoflow maintenance times at 1 l x s(-1) (IFMT1) and 2 l x s(
      1) (IFMT2) are recorded. The accuracy and reproducibility of the IFV technique
      were evaluated in 17 healthy adults (age 17-55 years) and in 14 asthmatic
      children (age 6-14 years). Comparisons with standard lung function parameters,
      such as forced expiratory volume in 1 s (FEV1), maximal expiratory flow at 50%
      (MEF50) and 25% (MEF25) vital capacity and peak expiratory flow (PEF), obtained
      with a Wright Peakflow Meter were undertaken in 102 healthy (aged 8-14 years) and
      101 asthmatic children (aged 6-17 years). A bronchial challenge test was
      performed in 13 asthmatic children. RESULTS: The expired volume measured by the
      IFW showed an acceptable agreement with that of a pneumotachograph (mean error of
      4.32% for IFMT1 and 5.93% for IFMT2). In healthy and in asthmatic children, the
      correlations between FEV1 and IFMT1 or IFMT2 (r = 0.92 and 0.94, respectively)
      were found to be greater than that between FEV1 and PEF (r = 0.68). During
      bronchial challenge tests in 13 asthmatic children, the FEV1 decreased to 69% of
      baseline and IFMT1 to 58% of baseline. CONCLUSIONS: The IFV technique accurately
      measured airway obstruction and closely followed changes in standard parameters
      of the MEFV curve.

PMID- 11287836
TI  - CT diagnosis of tracheobronchopathia osteochondroplastica.

PMID- 11287837
TI  - Colonization with Schizophyllum commune of localized honeycomb lung with mucus.
AB  - We report a surgical case involving localized honeycomb lung with mucus, caused
      by colonization of a Schizophyllum commune, which displayed a tumorous shadow in
      the right upper mediastinum. A 74-year-old male with a history of tuberculosis in
      the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an
      abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy
      failed to yield a definite diagnosis. We resected the right upper lobe, which was
      found to contain a consolidative lesion filled with viscous mucus in the right
      upper lobe adjacent to the right upper mediastinum. Microscopic examination
      revealed a honeycomb lung formation with mucus in the destroyed space. Culture of
      the mucus yielded a whitish filamentous fungus, positively identified as S.
      commune. This is the first report of S. commune leading to a deposit of mucus and
      the formation of a consolidative lesion in the destroyed lung.

PMID- 11287838
TI  - Pulmonary alveolar microlithiasis: a rare familial inheritance with report of six
      cases in a family. Contribution of six new cases to the number of case reports in
      Turkey.
AB  - Pulmonary alveolar microlithiasis (PAM) is a lung disease characterized by
      deposits of calcium within the alveoli. Our aim was to emphasize the familial
      character and the clinical features of the disease, and to draw attention to the
      increasing number of Turkish patients reported in the world. We detected 6 cases
      of PAM. Three cases had been diagnosed 4 years earlier, and 3 new cases were
      detected during the screening of the family members. All patients were male and
      the mean age was 11.5 ranging between 5 and 29 years. Five of the patients were
      cousins and the other one was their uncle. Radiographic studies showed a sand
      like appearance in all patients. One case showed small subpleural bullae and
      bronchiectatic changes in both lower lobes in recent high-resolution CT scans,
      while his CT performed 4 years ago showed only sand-like appearance. The cases
      were diagnosed with the demonstration of microliths by bronchoalveolar lavage in
      5 patients and transbronchial biopsy in 1. Recently reported cases from Turkey
      have constituted a considerable percentage among all cases in the world. In
      conclusion, (1) our patients constitute one of the largest series of cases
      reported in one family in the world. The disease seems to have familial and
      racial characteristics. The Turkish race has to be further investigated for
      genetic transmission. (2) Contrary to female predominance in previous reports,
      all 6 cases were male and 5 of them were below 12 years of age. (3) The disorder
      may show rapid progression in some cases probably due to the severity of the
      genetic disturbance.

PMID- 11287839
TI  - Improvement in right lung atelectasis (middle lobe syndrome) following
      administration of low-dose roxithromycin.
AB  - Middle lobe syndrome is a distinct clinical entity characterized by right middle
      lobe atelectasis. Prompt diagnosis and initiation of medical therapy including
      the administration of antibiotics and the avoidance of irritating agents may be
      effective. However, abnormal shadows on chest radiography remain unchanged even
      when acute symptoms have disappeared, suggesting latent lesional inflammation or
      recurrence. We describe 2 cases of atelectasis in the middle lobe of the right
      lung which resolved completely after administration of low-dose roxithromycin.
      Thus, low-dose therapy with a macrolide could be of interest or some value in
      these cases, but it is too early to draw a definite conclusion.

PMID- 11287840
TI  - Right hilar mass in a patient with beta-thalassemia major.

PMID- 11287841
TI  - The homeostatic role of bronchoconstriction.
AB  - This article argues in favour of the hypothesis that the homeostatic roles of
      bronchoconstriction are to retract the airway tree during expiration, and to
      assist in the expulsion of mucus from peripheral airways by increasing the
      velocity of outgoing air. In asthma, this function may be dangerously exaggerated
      because of the presence of unusually viscous airway secretions and the
      remodelling of airway walls.

PMID- 11287843
TI  - Effects of an NO-synthase inhibitor L-NMMA in the hepatopulmonary syndrome.

PMID- 11287842
TI  - Cytokine production by monocytes/macrophages is normal in patients with alveolar
      proteinosis: a report of two cases.

PMID- 11287844
TI  - Severe asthma attack in a patient with premenstrual asthma: hot pepper is the
      possible trigger.

PMID- 11287845
TI  - [Perspectives for Neuroradiology in France in the third millennium].

PMID- 11287846
TI  - [Diagnostic accuracy of the percutaneous spinal biopsy. Optimization of the
      technique].
AB  - Between 1992 and 1999, 210 percutaneous biopsies of the spine were performed in
      our department of neuroradiology. The purpose of this retrospective study was to
      determinate the diagnostic accuracy of the procedure and to discuss the technical
      points that might improve its accuracy. An accurate diagnosis was obtained in 72%
      of the spondylodiscitis and in 80% of the tumoral lesions (88% of metastatic
      lesions and 68% of primary tumors). These results have been compared with the
      other results of the literature. There was no significant difference of accuracy
      between CT and fluoroscopic guided biopsies. On the other hand, the type of
      needle and the multiplicity of samples for bacteriological and histologic studies
      improve the diagnostic accuracy.

PMID- 11287847
TI  - [Techniques for evaluating the degree of carotid artery stenosis].
AB  - Conventional angiography is considered to be gold standard for evaluating the
      degree of carotid artery stenosis. However, this technique carries a risk of
      complications. Thus, noninvasive techniques have been developed to avoid
      conventional angiography. Among these techniques, duplex sonography certainly
      constitutes the most attractive method, providing both morphological and
      hemodynamic data by combining different acquisition modalities. Contrast-enhanced
      MR angiography (MRA) is a recent development providing information on the
      intracranial and cervical vascularization in a short acquisition time. Previous
      studies have showed the reliability of this technique to detect severe carotid
      stenosis. Helicoidal CT is a third noninvasive method providing a reliable
      evaluation of carotid artery stenosis by analyzing both the axial CT images and
      the 3D reconstruction. However, CT angiography requires a radiation does and
      injection of an iodinated contrast agent. Moreover, the surrounding venous and
      bone structures may obscure evaluation of the arterial lumen.

PMID- 11287848
TI  - Relevance of diffusion and perfusion weighted mri for endovascular treatment of
      vasospasm in subarachnoid hemorrhage.
AB  - The endovascular treatment of vasospasm is effective when implemented rapidly.
      However its indication often proves difficult on account of the lack of
      diagnostic arguments or the difficulties in obtaining them in daily practice. We
      report a case that highlights the relevance of MRI in the decision-making
      process. A 37-year-old patient presented with symptomatic vasospasm of the middle
      cerebral artery and was subjected to morphological, diffusion- and perfusion
      weighted MRI. These investigations confirmed the presence of significant oligemia
      in the MCA territory and revealed onsetting diffusion disorders. Angioplasty was
      immediately performed, resulting in normal diffusion and hemodynamic parameters
      and complete regression of clinical signs. This case highlights the relevance of
      MRI when assessing vasospasm before treatment. Coupled with transcranial Doppler,
      it should help teams quickly select patients most likely to benefit from
      angioplasty.

PMID- 11287850
TI  - [Arteriography: chronicle of a predicted death?].

PMID- 11287851
TI  - [Macronodules, dysplastic nodules and cirrhosis].
AB  - For a few years, many descriptions and studies have been published regarding
      precancerous nodular liver lesions. As a result, several terms and
      classifications have been proposed leading to poor reproducibility. In 1995, an
      International Working Party defined nodular lesions called low grade and high
      grade dysplastic nodules. A good correlation between clinical, radiological and
      pathological lesions was then obtained. This article summarizes the
      histopronostic features of the nodules observed in cirrhotic liver, and attempts
      to specify the diagnostic criteria to distinguish dysplastic from regenerative
      macronodules and hepatocellular carcinomas.

PMID- 11287852
TI  - [Value of volume rendering in musculo-skeletal disorders].
AB  - Three dimensional imaging is increasingly important for evaluation of anatomic
      relationships and extent of disease, for treatment planning and for follow-up
      evaluation. The volume rendering technique allows creation of accurate 3D images
      that can be used for several clinical applications especially in musculo-skeletal
      disorders such as evaluation of tumors or fractures. This article describes the
      methods used for volume rendering technique and focuses on the specific aspects
      of volume rendering applied to musculo-skeletal applications.

PMID- 11287853
TI  - [Imaging mechanical complications of inferior vena cava filters].
AB  - Filter placement within the inferior vena cava is performed to prevent pulmonary
      embolism in patients with contraindications or failure of anticoagulant therapy.
      Several complications of vena cava filters have been described. However,
      mechanical complications related to IVC filters may not be of any clinical
      significance. The purpose of this pictorial essay is to present the imaging
      features of complications related to inferior vena cava filter placement.

PMID- 11287854
TI  - [Comparison between arteriography and magnetic resonance angiography in patients
      with leg peripheral arterial disease ].
AB  - PURPOSE: The anatomic information before surgical therapy must be precise.
      Contrast angiography fails to opacify distal vessels in a large number of cases.
      We have evaluated the capability of magnetic resonance angiography to depict
      peripheral arteries. Materials and methods. We examined fourty-eight patients. CA
      was performed from a femoral or humeral approach, with or without subtraction.
      MRA were obtained using a 1.5 T magnet. Ankles and feet were placed in a head
      coil; three sequences were performed: Reconstructions and axial source images
      were reviewed. RESULTS: MRA is superior to CA to demonstrate patent arterial
      segments in a majority of cases. CONCLUSION: MRA is an effective method to
      identify distal lower extremity arteries.

PMID- 11287855
TI  - [Contrast-enhanced MRA of the carotid arteries using 0.5 Tesla: comparison with
      selective digital angiography].
AB  - PURPOSE: To assess the feasability, the imaging quality and the effectiveness of
      contrast-enhanced MRA (CE MRA) using a 0.5 Tesla MR unit in the evaluation of
      internal carotid artery (ICA) stenosis. Materials and Methods. 29 patients
      underwent CE MRA and selective digital substraction angiography (DSA). All data
      were reviewed in a blinded fashion by 2 independant observers. Imaging quality
      was graded as good, moderate but interpretable, and insufficient. Stenosis was
      graded according to the NASCET classification from grade 1 to 4, with the
      following thresholds:<30%,<70%,<99% and occlusion. Inter and intra- observer
      agreement was evaluated using the kappa index. RESULTS: Imaging quality was good
      for 79 arteries, moderate for 24 and insufficient for 13 (k MRA=0.72 and 0.64
      respectively for the right and left ICAs). Interobserver agreement was good with
      values for right/left ICA of 0.84/0.94, 0.72/0.74 respectively for CE-MRA and
      DSA. For the comparison between CE MRA and DSA, agreement was also good, with
      values of 0.74 and 0.64 for both readers. Sensitivity of CE MRA in the detection
      of hemodynamically significant stenosis (>70%) was of 0.95 and 0.94 and specifity
      of 0.91 and 0.89 respectively for reader n degrees 1 and reader n degrees 2.
      CONCLUSION: CE MRA using a 0.5T MR unit is a valuable technique in the evaluation
      of ICA stenosis.

PMID- 11287856
TI  - [Incremental lower extremity CT venography, a simplified approach for the
      diagnosis of phlebitis in patients with pulmonary embolism].
AB  - PURPOSE: To demonstrate that incremental CT venography, performed at the time of
      CT pulmonary angiography, can easily diagnose deep venous thrombosis. Materials
      and Methods. Retrospective analysis of 152 combined incremental CT venography and
      CT pulmonary angiography. Results were compared to Doppler US examinations in 18
      cases. RESULTS: 61% of venous thrombosis was found on incremental CT examination
      in case of pulmonary embolism. In 5 cases, isolated venous thrombosis was found
      without pulmonary embolism. The CT diagnosis of DVT was confirmed by US; CT
      appeared more accurate than US in the calf. CONCLUSION: CT venography combined
      with CT pulmonary angiography is a useful tool in order to obtain a comprehensive
      evaluation for thrombo-embolic disease.

PMID- 11287857
TI  - [Tuberculous osteitis of the posterior vertebral arch: case report].
AB  - The authors report an unusual case of spinal tuberculosis involving the posterior
      arch of T12 without disk lesion in a 20-year-old woman presenting with posterior
      compression of the spinal cord. The diagnosis was suggested at CT and MR imaging
      and confirmed by histological study after surgical resection. CT provides good
      evaluation of the bony lesion and may suggest intraspinal extension. MRI is
      superior for evaluation of cord compression. The patient improved after surgical
      and medical treatment. The imaging features of this entity are reviewed.

PMID- 11287858
TI  - [Meckel's diverticulitis in the adult: diagnosis by computed tomography].
AB  - The authors report a case of acute Meckel's diverticulitis diagnosed by CT in a
      38 year old patient. The authors describe the value of CT for diagnosis and
      evaluation of disease extent in a patient presenting with non specific symptoms.

PMID- 11287859
TI  - [Lactating adenoma: radiologic aspects. A case report].
AB  - We report the US and MRI appearance in a patient with a giant lactating adenoma
      detected during pregnancy and followed-up for 12 months postpartum. The different
      imaging features of lactating adenomas are discussed, especially at US and MRI.
      We discuss also the role of core biopsy in diagnosing pregnancy associated breast
      masses.

PMID- 11287860
TI  - [Pre- and postnatal diagnosis of omphalo-xiphopagus conjoined twins].
AB  - We report a case with successful surgical separation of female omphalo-xiphopagus
      conjoined twins. Ultrasonographic examination at 20 weeks of gestation showed
      twins joined at the abdomen from the xiphoid process to the umbilicus. Conjoined
      structures included liver. Karyotype was normal. The parents refused interruption
      of the pregnancy. Plain films, US and MRI confirmed findings at prenatal
      ultrasound examination. There was no cross circulation into the livers and the
      gastrointestinal tract was not conjoined. In our observation, postnatal MRI did
      not offer additional information.

PMID- 11287861
TI  - [Percutaneous treatment of a common iliac aneurysm extending to the hypogastric
      artery with embolization and a covered endoprosthesis].
AB  - A case of iliac aneurysm treated percutaneously by endovascular stent graft
      (Wallgraft - Boston) and transcatheter embolization of internal iliac artery in
      order to prevent retrograde filling of the aneurysm from the patent hypogastric
      artery is presented. The initial radiographic evaluation included arteriography,
      and 2D and 3D spiral CT angiograms. This enabled analysis of the extent of mural
      thrombus, flow direction, as well as selection of stent graft and coil size. The
      procedure of embolization and implantation was technically uneventful. Post
      procedure 3D CT and arteriography demonstrated exclusion of the aneurysm, and
      return to a normal flow pattern. Follow-up at 6 and 12 months confirmed the
      stability of the results. Percutaneous treatment of common iliac artery aneurysms
      involving the hypogastric artery can be performed easily, especially in elderly
      patients. 3D CT is essential in assessing the endo and extra luminal
      characteristics of the aneurysm to insure optimal results and to detect
      complications.

PMID- 11287862
TI  - [Osteoarticular imaging of tomorrow].

PMID- 11287863
TI  - [Shoulder imaging: what is the best modality?].
AB  - Specific pathologies of the shoulder include instabilities in young patients and
      tendinopathies in older patients. The choice of imaging modality depends on the
      information expected from each technique. In case of instability, plain films
      demonstrate bone abnormalities such as Hill Sachs and/or Bankart lesions. Arthro
      CT or arthro-MRI need not be in all cases but can provide additional information
      performed about the intraarticular structures and the glenoid labrum. The rotator
      cuff is initially evaluated by plain films which demonstrate anatomical
      conditions resulting in impingement syndrome as well as indirect signs of
      tendinopathy. Direct visualization of tendons may be achieved by US, arthro-CT,
      arthro-MRI. US is a dynamic, non invasive and accurate technique for evaluation
      of rotator cuff tear but is very operator-dependent. Arthro-CT is more
      reproductive and reveals accurately partial tear as well as anterior tears
      involving biceps or subscapularis tendons. MRI is very useful to visualize the
      rotator cuff and adjacent bony structures. Nevertheless, MRI is still limited by
      its cost, accessibility and variable quality.

PMID- 11287864
TI  - [Imaging of the wrist and of the hand: what is the best modality?].
AB  - The authors describe the indications for radiologic explorations in case of
      traumatic as well as non-traumatic conditions. In case of trauma of the wrist,
      the radiologic exploration looks for a fracture, a dislocation or a ligament
      injury. Initially, postero-anterior and lateral views must be completed with an
      antero-posterior view, a scaphoid incidence and an oblique view. This initial
      examination can be completed secondarily by specific views for the carpal bones,
      dynamic X-Rays, CT scan or arthro CT scan. In non-traumatic cases, radiologic
      explorations look for osteo-articular or soft tissue abnormalities specific of a
      inflammatory or degenerative disease. The initial incidence is a postero-anterior
      view of both hands. It can be completed secondarly by other explorations (other X
      Rays, Ultra-sound, CT scan or MRI).

PMID- 11287865
TI  - [Radiography of the upper limb revisited: the shoulder and the wrist].
AB  - CT scan and MR imaging are the most efficient techniques to evaluate the upper
      limb, however, standard radiography remains a valuable method to explore this
      anatomical region. In most situations, it is sufficient to allow a precise
      diagnosis and determine therapeutic protocols. However, this method can present a
      real diagnostic value only when it is guided by medical history and clinical
      data. The purpose of this work is to propose a practical approach for
      radiographic evaluation of the shoulder and the wrist, suited to the main
      clinical situations. CT-scan and MR imaging correlations will help to understand
      radiographic findings.

PMID- 11287866
TI  - [Hip imaging: what is the best modality?].
AB  - Conventional radiography plays a key-role in the assessment of symptomatic hips.
      A well-performed radiographic examination (comparative A-P views with straight or
      ascending X-Ray beam, off-lateral view of Lequesne) enables to recognise most
      bone (fractures, transient osteoporosis, epiphyseal osteonecrosis) and articular
      lesions (osteoarthritis). In some situations (incoherent radio-clinical findings,
      need of a confident diagnosis), joint aspiration or additional imaging procedures
      are needed. Serial radiographs are obtained when no specific treatment can be
      immediately offered. Bone scintigraphy is obtained to confidently exclude bone or
      articular disorders or in case of suspected disseminated bone disease. The
      majority of bone, articular and abarticular lesions can be diagnosed by using
      MRI. It should be obtained when results are likely to influence the final outcome
      of the disease.

PMID- 11287867
TI  - [Knee imaging: what is the best modality].
AB  - A wide range of exams are available for imaging the knee: standard radiography,
      ultrasound, bone scintigraphy, CT scan, arthroscan, MRI, arthro-MRI. The
      radiologist must be aware of the performance capacities of each technique in
      order to orient the clinician's choice towards the most appropriate exam in a
      given clinical situation. In the first part of this paper, we examine the
      performances, advantages and disadvantages of each technique: exam conditions
      (patient position, incidence, slice thickness, sequence.) are detailed as
      required. The second part is a practical guide for some typical clinical
      situations with decision trees for ordering necessary and sufficient
      explorations.

PMID- 11287868
TI  - [Foot and ankle imaging: what is the best modality].
AB  - There are numerous foot and ankle's pathologies and also numerous imaging
      technics. In fact, it often appears an inadequacy between the suspected pathology
      and the diagnostic tool used for its study. Aims. Know the qualities and the
      faults of each foot and ankle imaging technic. Know the best way of using these
      technics, according to the clinical problem, of a medical and economic point of
      view, in main skeletal pathologies, mechanical arthropathies of the hindfoot,
      tendonopathies, infections, and forefoot diseases.

PMID- 11287869
TI  - [Normal and pathologic symphysis pubis: value of imaging].
AB  - The pubic symphysis is a region which has been little or poorly investigated by
      imaging. It is however electively and primarily affected by many micro and macro
      trauma and is a convenient witness of more general disorders, in particular
      rheumatological. After a brief anatomical and biomechanical review, the principal
      pathological aspects are set out.

PMID- 11287870
TI  - Aging in the gastrointestinal tract.

PMID- 11287871
TI  - Research Priorities Project, year 2000: the Lone Ranger rides again.

PMID- 11287872
TI  - Research Priorities Project, year 2000: establishing a direction for infection
      control and hospital epidemiology.
AB  - BACKGROUND: The field called "infection control" has expanded beyond hospitals to
      include many health care locations, some aspects of personnel health, elements of
      noninfectious complications, and occasionally the epidemiology of other problems
      that occur in care facilities. A research agenda that addresses these newer
      segments and provides a framework for answering fundamental questions is
      essential for the field and for the work of The Research Foundation for
      Prevention of Complications Associated with Health Care (formerly APIC Research
      Foundation). METHODS: We used a multiple-round iterative consensus process
      (Delphi technique) with 50 experts and a validation round among participants at
      the 4th Decennial Conference. RESULTS: The expert panel reduced 102 separate
      items to 21 high-ranked research priorities. The highest-ranked subject areas
      involved research to improve compliance with excellent practices, to study
      antibiotic usage and resistance, to measure the financial impact of complications
      and value of interventions, to perform surveillance of infectious and
      noninfectious complications across the spectrum of care delivery, and to study
      effectiveness of interventions to prevent complications at specific sites. There
      were differences in education and discipline between the expert panel and the 4th
      Decennial participants and with respect to ranking some of the individual
      priorities. Among respondents from outside the United States and Canada,
      occupational health issues were ranked more highly. CONCLUSIONS: The research
      priorities provide a blueprint for future progress and will require a
      collaborative, multicenter, multinational approach.

PMID- 11287873
TI  - Incidence and determinants of Pseudomonas aeruginosa infection among persons with
      HIV: association with hospital exposure.
AB  - BACKGROUND: Little information exists on risk factors for Pseudomonas aeruginosa
      infection in persons with HIV. We assessed the incidence and factors associated
      with P aeruginosa among persons with HIV enrolled in a large observational cohort
      study in Los Angeles. METHODS: Data were analyzed from 4825 persons aged > or =13
      years with HIV infection enrolled from 4 outpatient facilities from 1990 to 1998.
      The association between P aeruginosa infection and demographic, risk behavior,
      and clinical factors was assessed. RESULTS: P aeruginosa was diagnosed in 72
      (1.5%) patients representing a crude incidence rate of 0.74 per 100 person-years.
      The most frequent site of infection was pulmonary (47%). In multivariate
      analysis, prior hospitalization (adjusted rate ratio = 7.9, 95% CI, 3.8-16.2),
      and both dapsone (adjusted rate ratio = 4.0, 95% CI, 2.2-7.4) and trimethoprim
      sulfamethoxazole (adjusted rate ratio = 2.5, 95% CI, 1.2-5.3) use were
      independently associated with higher rates of infection. Increasing days of
      inpatient stay (P <.01) and decreasing CD4(+) counts (P <.01) were strongly
      associated with P aeruginosa. Azithromycin use decreased the risk of infection by
      nearly 70%. CONCLUSION: Although the overall observed incidence of P aeruginosa
      was low, hospital exposure, declining CD4(+) levels, and the use of dapsone or
      trimethoprim-sulfamethoxazole increased the risk of P aeruginosa disease, and
      azithromycin use was protective in this population. These findings may assist in
      the early recognition and diagnosis of persons likely to be at increased risk of
      P aeruginosa infection.

PMID- 11287874
TI  - Impact of antibiotic prophylaxis on wound infection after cesarean section in a
      situation of expected higher risk.
AB  - BACKGROUND: To measure rates of incisional surgical site infection (ISSI) after
      cesarean section (CS) and to assess risks for infection. METHODS: Prospective
      surveillance for ISSI at a 540-bed hospital in Saudi Arabia by using Centers for
      Disease Control and Prevention definitions for infection and the National
      Nosocomial Infections Surveillance (NNIS) system risk index. RESULTS: Seven
      hundred thirty-five CSs were studied from September 1998 to July 1999; 72% were
      emergency procedures, despite a 95% rate of antenatal care. The overall ISSI rate
      was 2.8% (95% confidence interval [CI], 1.7%-4.3%). The rate for NNIS risk
      category 0 was 2.4% (95% CI, 1.3%-4.2%; n = 536) and for category 1 was 4.1% (95%
      CI, 1.8%-8.6%; n = 170). In the multivariate analysis, the only independent risks
      for ISSI were duration of surgery (OR = 1.01; 95% CI, 1.00-1.03; P =.02) and no
      antibiotic prophylaxis (OR = 3.09; 95% CI, 1.10-9.11; P =.04). Antibiotic
      prophylaxis was inconsistently administered among both emergency and elective CS.
      Infection control procedures were inadequate in the obstetric suite operating
      room. CONCLUSIONS: Despite deficient infection control practices in the setting
      described, ISSI rates after CS were judged "acceptable" compared with NNIS
      benchmark rates. This was attributed to prescribing antibiotic prophylaxis for
      patients at low risk as well as high risk of infection.

PMID- 11287875
TI  - Implementing and evaluating a rotating surveillance system and infection control
      guidelines in 4 intensive care units.
AB  - BACKGROUND: In clinical practice, scientific evidence about infection control is
      often ignored and hygiene rituals are followed. METHODS: Within an evidence-based
      infection control program, a quarterly rotating surveillance program for
      nosocomial infections was implemented in 4 intensive care units (ICUs) at the
      Aachen University Hospital, Germany. RESULTS: For the first time, the unit
      specific nosocomial infection situation was made clear to the clinical staff by
      interpretive feedback of the surveillance data. This led to an increased
      awareness of infection control and a critical review of hygiene practices. After
      the first surveillance period, the hygiene practices of each ICU were revised and
      modified. The Centers for Disease Control and Prevention/Hospital Infection
      Control Practices Advisory Committee guidelines for the prevention of nosocomial
      infections were adopted and established in tight collaboration with the ward
      staff. CONCLUSIONS: Within the surveillance process, communication and team
      spirit between infection control and patient care personnel showed a remarkable
      improvement. Awareness and compliance with hospital hygiene and infection control
      practices could be raised without directive interaction.

PMID- 11287876
TI  - Unique epidemiology of nosocomial urinary tract infection in children.
AB  - BACKGROUND: Nosocomial urinary tract infection (NUTI) occurs with varying
      frequency in children and is thought to be associated with urethral
      instrumentation. In response to changing infection control resources at our
      facility, we reviewed NUTI to determine whether the frequency of NUTI, associated
      complications, or presence of a remediable risk factor (instrumentation)
      justified ongoing routine infection control surveillance. METHODS: Prospective
      surveillance was conducted on all wards 8 months per year from January 1991
      through December 1997 by an infection control nurse coordinator. NUTI was defined
      by laboratory evidence according to Center for Disease Control and Prevention
      definitions and detected 48 hours after admission. Urinary catheterization in the
      previous 7 days was categorized as continuous/indwelling or intermittent.
      RESULTS: NUTI was the fifth most common nosocomial infection (129/1375;
      approximately 9%) and decreased in frequency during the decade from 0.9 to
      approximately 0.6 cases/1000 patient days. Incidence was equal among men and
      women. Only 50% of cases had prior instrumentation of the urinary tract. NUTI
      occurred disproportionately in newborns and infants (P <.001). The most common
      pathogen was Escherichia coli (28%; 38/132), followed by Candida sp (18%;
      24/134), Enterococcus (13%; 18/134), gram-negative nonfermenters (13%; 17/132),
      Enterobacter (approximately 10%; 13/134), Pseudomonas (9.7%; 13/134), and other
      (16%; 22/134). Three cases of secondary bacteremia occurred (2.3%; 95% confidence
      interval 0.5-6.6); there was no mortality. CONCLUSIONS: NUTI poses a less
      significant burden of illness (incidence, associated morbidity) than other
      nosocomial infection in children. If resources do not permit hospital-wide
      surveillance, high-risk children with urethral instrumentation and newborns and
      infants could be targeted. Although E coli remains the most common cause of
      pediatric NUTI, fungi have become the second most common pathogen in this
      tertiary care population. Risk factors for NUTI in noncatheterized children
      remain to be delineated.

PMID- 11287877
TI  - Surgical site infections in ambulatory surgery: a 5-year experience.
AB  - OBJECTIVES: To evaluate the ambulatory surgical site infection rate and risk
      factors associated with surgical site infection. METHODS: We conducted a case
      control analysis of all ambulatory surgeries between January 1, 1993, and
      December 31, 1997. The frequency of surgical site infection per 100 surgeries was
      calculated. The odds ratio (OR) was estimated by using logistic regression
      analysis. SETTING: A 140-bed tertiary-care teaching hospital for adult patients
      with cancer. RESULTS: The study followed 1350 outpatient surgeries. Thirty-eight
      patients had a surgical site infection (rate per 100 surgeries: 2.8). The risk
      factors statistically associated with surgical site infection were postoperative
      antibiotics (OR = 7.5; 95% CI, 2.5-23.0), and surgical time >35 minutes (OR =
      2.4; 95% CI, 1.1-5.5). CONCLUSIONS: The surgical site infection rate for same-day
      surgery at our hospital is within the limits reported in the literature and below
      the rates reported previously for inpatient surgeries at our hospital. Full
      review of medical records and microbiology reports at day 30 allowed us to
      identify infections that otherwise would have been missed. Postoperative
      antibiotics may increase the risk of infection.

PMID- 11287878
TI  - Pseudoepidemic of streptococcal pharyngitis in a hospital pharmacy.
AB  - CONTEXT: Streptococcus pyogenes has recently re-emerged as a significant pathogen
      causing disease ranging from pharyngitis to lethal systemic infection. Six
      hospital pharmacy employees were diagnosed as having streptococcal pharyngitis
      during 1 week, and antibiotic prophylaxis was requested to halt the outbreak.
      OBJECTIVE: Outbreak investigation. DESIGN: Review of initial cases and
      prospective evaluation of the remaining pharmacy employees and the antigen
      detection test being used. SETTING: Pharmacy and occupational health department
      of a university hospital. POPULATION: Sixteen employees of the hospital pharmacy
      and 19 other employees of the hospital. RESULTS: The 6 pharmacy employees who had
      positive streptococcal antigen detection tests did not have symptoms suggesting
      streptococcal pharyngitis. Of the 10 remaining pharmacy employees, none had a
      positive throat culture for S pyogenes. Specificity of the antigen detection test
      being used was 53% (95% CI, 30%-75%) in prospective evaluation. CONCLUSIONS: This
      was believed to represent a pseudoepidemic because none of the 6 cases had signs
      or symptoms typical of streptococcal pharyngitis, none of the remaining 10
      pharmacy employees had positive throat cultures, and prospective evaluation found
      low specificity of the antigen detection test. Whereas use of an accurate test in
      such a low prevalence setting could have resulted in a higher percentage of
      results being false-positive, the low specificity of the antigen detection test
      being used also contributed to the pseudoepidemic.

PMID- 11287879
TI  - Risk factors for nosocomial infections in critically ill newborns: a 5-year
      prospective cohort study.
AB  - BACKGROUND: Nosocomial infections (NIs) are one of the most important causes of
      morbidity in neonatal intensive care units (NICUs). The aim of this study was to
      identify risk factors (RFs) for NIs among critically ill newborn patients in a
      Brazilian NICU. METHODS: This 5-year prospective cohort study in an 8-bed NICU
      included all infants born in the hospital and admitted to the NICU from 1993 to
      1997. Exposure variables were maternal and newborn data prospectively collected
      from patient records. Univariate and multivariate analyses were used to determine
      independent RFs associated with NIs. RESULTS: Univariate analysis indicated
      gestational age, congenital abnormality, premature rupture of membranes, maternal
      illness, birth weight, mechanical ventilation, central venous catheter, total
      parenteral nutrition, peripheral venous catheter, and length of stay as possible
      RFs. Multivariate analysis identified 5 independent RFs for NIs: premature
      rupture of membranes (hazard ratio [HR] = 1.51 [95% CI, 1.15-1.99]), maternal
      disease (HR = 1.57 [95% CI, 1.18-2.07]), mechanical ventilation (HR = 2.43 [95%
      CI, 1.67-3.53]), central venous catheter (HR = 1.70 [95% CI, 1.21-2.41]), and
      total parenteral nutrition (HR = 4.04 [95% CI, 2.61-6.25]). CONCLUSION: The
      recognition of RFs for NIs is an important tool for the identification and
      development of interventions to minimize such risks in the NICU.

PMID- 11287880
TI  - Serratia marcescens transmission in a pediatric intensive care unit: a
      multifactorial occurrence.
AB  - BACKGROUND: Fourteen patients in the pediatric cardiac intensive care unit (CICU)
      had > or =1 positive culture for a single strain of Serratia marcescens from
      April through December 1995 (study period). OBJECTIVES: To identify risk factors
      for S marcescens infection or colonization in a pediatric CICU. METHODS:
      Retrospective case-control study. Assessment of CICU infection control practices
      and patient exposure to CICU health care workers (HCWs). Epidemiologic-directed
      cultures of the environment and HCWs' hands were obtained. SETTING: Pediatric
      CICU. PATIENTS: Fourteen patients in the pediatric CICU had > or =1 positive
      culture for a single strain of S marcescens from April through December 1995
      (study period). CICU patients who did not have S marcescens infection or
      colonization during the study period were randomly selected as controls. RESULTS:
      A case patient was more likely than a noncase patient to have exposure to a
      single HCW (odds ratio [OR], 19.5; 95% CI, 2.6-416; P<.003); however, this
      association was not adequately explained by epidemiologic or microbiologic
      studies. Interviews suggested that during the outbreak period, handwashing
      frequency among HCWs might have been reduced because of severe hand dermatitis.
      CONCLUSIONS: A combination of factors, including breaks in aseptic technique,
      reduced frequency of handwashing among HCWs before and between caring for
      patients, decreased attention to infection control practices, and environmental
      contamination may have indirectly contributed to this S marcescens infections
      outbreak.

PMID- 11287881
TI  - Tetanus IgG antibody levels in children aged 12 to 47 months in Turkey.
AB  - Tetanus is a serious disease with high mortality, which is very difficult to
      treat but can be prevented easily by vaccination. The number of tetanus cases
      reported in Turkey was 42 in 1996 and 51 in 1997. This study was carried out on
      children aged 12 to 47 months who have vaccination cards in the No. l Health
      Centre in Batikent district in Ankara, Turkey. Forty-one of the children had
      received 3 doses (Group 1) of tetanus vaccine, and 47 of them had received 4
      doses of the vaccine (Group 2). Anti-toxoid IgG antibody in blood sera was
      quantified by using the enzyme-linked immunosorbent assay technique. In Group 1,
      antibody levels more than 0.01 IU/mL were found in 47%, 43%, and 45% of blood
      sera of children aged 12 to 23 months, 24 to 35 months, and 36 to 47 months,
      respectively. These rates in Group 2 were found to be 91%, 88%, and 60%,
      respectively. The protective antibody response (>1 IU/mL) was found to be higher
      for children in Group 2 than in Group 1, but both rates declined with age.
      Checking immunization status periodically and giving vaccine doses as required
      are essential to increase the antibody response. Further, it is a must in
      developing countries where vaccination efforts are hindered by cold-chain
      problems, underoptimum application practice, and high prevalence of concomitant
      infections.

PMID- 11287882
TI  - Antibacterial efficacy of triclosan-incorporated polymers.
AB  - Triclosan (2, 4, 4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum
      antimicrobial agent, routinely used in various personal care products.(1) It is
      also incorporated into polymers through melt-mixing, with the aim of providing
      persistent antibacterial action on the surface of the polymer.(2,3) Such
      triclosan-incorporated polymers can be promoted for hospital use as fabric seat
      covers, tables, chairs, and clothing. We assessed the antibacterial efficacy of
      triclosan-incorporated polymer disks against 2 bacteria cultured in liquids in
      contact with the polymer. In spite of the relatively high concentrations of
      triclosan in the polymer, only some initial slowing of the bacterial growth rates
      was observed, followed by the absence of an antibacterial effect over extended
      periods. The triclosan at the surface of the disks dissolves into the liquids,
      and the rest of the triclosan, immobilized in the disks, does not contribute to
      the antibacterial effectiveness of triclosan-incorporated polymer. In light of
      recent studies, which have shown that triclosan acts on a specific target within
      the bacterial lipid synthesis pathway, triclosan-incorporated polymers may
      provide the ideal setting for resistant strains of bacteria to grow and thus
      should be used selectively in hospital environments.

PMID- 11287883
TI  - Paenibacillus macerans pseudobacteremia resulting from contaminated blood culture
      bottles in a neonatal intensive care unit.
AB  - Paenibacillus species are gram-positive, rod-shaped, spore-forming aerobes that
      are abundant in nature and closely related to Bacillus. Between June 24 and June
      30, 1999, 8 neonates in our neonatal intensive care unit had positive blood
      cultures for Paenibacillus macerans. This cluster of positive blood cultures with
      an unusual pathogen suggested a pseudoepidemic. Investigation revealed that the
      most likely etiology of the pseudobacteremia was environmental contamination of
      the rubber stoppers in blood culture bottles. This was confirmed by environmental
      sampling and simulated inoculation studies. This pseudobacteremia outbreak
      highlights the importance of adhering to well-established methods for blood
      culture collection and ongoing infection control surveillance.

PMID- 11287884
TI  - Infection control staffing patterns.

PMID- 11287885
TI  - Dealing with contaminated computer keyboards and microbial survival.

PMID- 11287886
TI  - Be careful what you look for.

PMID- 11287887
TI  - Serial Doppler echocardiographic assessment of left and right ventricular
      performance after a first myocardial infarction.
AB  - We sought to investigate the relation between left ventricular (LV) and right
      ventricular (RV) function assessed with the Doppler-derived myocardial
      performance index (MPI), to assess serial changes, and to investigate the
      prognostic value of biventricular assessment of cardiac function after a first
      myocardial infarction (MI). To do so, serial Doppler echocardiography was
      performed in 77 consecutive patients with a first MI. Right ventricular MPI
      correlated significantly with LV MPI (r = 0.51, P <.0001). In patients with
      echocardiographic signs of RV MI, the RV MPI was significantly higher (0.59 +/-
      0.18 versus 0.44 +/- 0.19, P =.001), whereas no difference in LV MPI was seen
      (0.55 +/- 0.19 versus 0.56 +/- 0.13, P = not significant). Right ventricular MPI
      showed a rapid normalization during follow-up, whereas LV MPI did not decrease.
      During follow-up, 23 patients died of cardiac causes or were readmitted because
      of worsening heart failure. Multivariate Cox analysis indicated LV MPI (relative
      risk 4.9 [95% CI 1.8-13.5], P =.002) and RV MPI (relative risk 3.8 [1.3-17.0], P
      =.01) to be predictors of cardiac events. Thus the RV MPI is frequently abnormal
      after a first MI but normalizes rapidly on follow-up, and biventricular
      assessment of cardiac function may improve the prognostic accuracy compared with
      LV assessment alone.

PMID- 11287888
TI  - Cardiorespiratory exercise capacity and its relation to a new Doppler index in
      children previously treated with anthracycline.
AB  - The purpose of this study was to assess the exercise capacity of patients treated
      with anthracycline and to evaluate the relation between the exercise capacity and
      a new Doppler index. The study patients consisted of 70 subjects: 41 healthy
      subjects and 29 who had been treated with various cumulative doses of
      anthracycline (range 45 to 873 mg per body surface area). The following
      conventional echocardiographic parameters were measured: rate-corrected mean
      velocity of fiber shortening (mVcfc), end-systolic wall stress (ESS), stress
      velocity index, and early and late diastolic mitral inflow velocities and their
      ratio. A new Doppler index, the Tei index, was calculated as the sum of
      isovolumic contraction time and isovolumic relaxation time divided by the
      ejection time. Peak oxygen uptake (pVo(2)) and anaerobic threshold (AT) were
      measured during an upright bicycle exercise test. The pVo(2) and AT in the
      patient group were significantly lower than those in the control group (pVo(2):
      22.0 +/- 3.7 versus 28.5 +/- 7.1 mL/min/kg; AT: 12.7 +/- 1.9 versus 17.3 +/- 4.3
      mL/min/kg, respectively; P <.01). There were no significant differences in the
      mVcfc, ESS, stress-velocity index, E wave, A wave, or E/A wave ratio between the
      two groups. However, the mean Tei index of the patients was significantly greater
      than that of the controls (0.41 +/- 0.11 versus 0.33 +/- 0.04, P <.01). The
      pVo(2) and AT decreased significantly with an increase in the Tei index (r = 
      0.64 and -0.60, respectively; P <.01). A weak positive correlation was found
      between the AT and E/A wave ratio (r = 0.54, P <.05). However, no significant
      correlations were seen between the exercise parameters and the mVcfc, ESS, stress
      velocity index, or transmitral velocities. Our findings suggest that
      cardiopulmonary exercise testing revealed an inverse correlation between exercise
      capacity and the Tei index.

PMID- 11287889
TI  - Strain rate imaging in normal and reduced diastolic function: comparison with
      pulsed Doppler tissue imaging of the mitral annulus.
AB  - OBJECTIVES: The pixel velocity values obtained by color Doppler tissue imaging
      (DTI) can be processed to velocity gradients as a measure of longitudinal strain
      rate with a technique termed strain rate imaging (SRI). Color mapping of strain
      rate does show the spatial-temporal relations of the diastolic phases. The phases
      of early filling and late filling during atrial systole can be seen to consist of
      a stretch wave in the myocardium, propagating from the base to the apex.
      Diastolic function is characterized by both peak strain rate and propagation
      velocity of this wave. The goals of this study were to establish normal values
      for these measurements and to study the changes with minimal diastolic
      dysfunction. METHODS: Twenty-eight healthy control subjects and 26 patients with
      hypertension and normal systolic function were studied. The patients had normal
      blood pressure on treatment, normal ejection fraction, minimal hypertrophy, and
      moderately prolonged deceleration and isovolumic relaxation times. Real-time SRI
      color cineloops, ordinary echocardiography and Doppler recordings, and pulsed
      wave DTI from the mitral ring were acquired and processed. RESULTS: Patients
      showed a reduction of systolic and early diastolic tissue velocities and strain
      rates and no significant increase in late diastolic tissue velocity and strain
      rate. Propagation velocity of diastolic strain during both early and late filling
      phases was reduced in the patients. The combination of changes in peak strain
      rate and propagation velocity of strain rate corresponded with changes in DTI.
      CONCLUSION: Diastolic deformation of the ventricle can be shown as a complex
      series of events, with temporal sequences in the ventricle. The peak strain rate
      and the propagation velocities of strain rate can describe the two main diastolic
      events: early and late filling. In reduced diastolic function, both are reduced
      during early filling. The velocities of the mitral ring are the result of this
      combination. This adds information about the physiology and pathophysiology of
      diastole.

PMID- 11287890
TI  - Assessment of left ventricular function by real-time 3-dimensional
      echocardiography compared with conventional noninvasive methods.
AB  - Quantitative assessment of left ventricular ejection fraction is an essential
      component of cardiac evaluation. We performed real-time 3-dimensional
      echocardiography in 56 consecutive patients who underwent multigated radionuclide
      angiography. Thirteen patients were excluded for the following reasons: 5 for
      large size of left ventricle required for image acquisition, 5 for suboptimal
      image quality in real-time 3-dimensional echocardiography, and 3 for atrial
      fibrillation. Finally, we compared left ventricular ejection fraction assessed by
      real-time 3-dimensional echocardiography and conventional 2-dimensional
      echocardiography with that obtained by multigated radionuclide angiography in 43
      patients. Left ventricular ejection fraction was determined by real-time 3
      dimensional echocardiography with the use of parallel plane-disks and sector
      plane-disks summation methods. A good correlation was obtained between both real
      time 3-dimensional echocardiography methods and multigated radionuclide
      angiography (r = 0.87 and 0.90, standard error of estimate = 3.7% and 4.2%),
      whereas the relation between the 2-dimensional echocardiography method and
      radionuclide angiography demonstrated a significant departure from the line of
      identity (P <.001). In addition, interobserver variability was significantly
      lower (P <.05) for the real-time 3-dimensional echocardiography methods than that
      by the 2-dimensional echocardiography method. Real-time 3-dimensional
      echocardiography may be used for quantification of left ventricular function as
      an alternative to conventional methods in patients with adequate image quality.

PMID- 11287891
TI  - Correlation between quantitative left atrial spontaneous echocardiographic
      contrast and intact fibrinogen levels in mitral stenosis.
AB  - An association between left atrial spontaneous echocardiographic contrast (LASEC)
      and thromboembolic events has been recognized. However, the appearance of LASEC
      and the assessment of its intensity are gain dependent. To evaluate the relation
      between LASEC intensity and coagulation activity, 11 patients with mitral
      stenosis underwent transesophageal echocardiography with quantitative integrated
      backscatter assessment of LASEC. Right and left atrial blood samples were
      evaluated for concentrations of coagulation markers, including intact fibrinogen,
      fibrinopeptide A, D-dimer, prothrombin fragment 1+2, and thrombin-antithrombin
      III complex. The patients were found to have significantly higher mean left
      atrial concentrations compared with right atrial concentrations of thrombin
      antithrombin III (28.46 +/- 21.05 versus 3.21 +/- 7.16 ng/mL, respectively; P
      =.001) and fibrinopeptide A (32.78 +/- 17.54 versus 7.42 +/- 8.27 nmol/L,
      respectively; P <.001). Intact fibrinogen levels were similar in both atria, and
      a strong, direct correlation existed between left and right atrial intact
      fibrinogen levels (r = 0.78, P =.005). Quantitative integrated backscatter of
      LASEC correlated directly with left atrial fibrinogen level (r = 0.78, P =.013)
      but not with markers of thrombin generation (thrombin-antithrombin III) or
      activity (fibrinopeptide A). Our results confirm that patients with mitral
      stenosis have evidence of a regional hypercoagulable state in the left atrium.
      However, the intensity of LASEC assessed by quantitative integrated backscatter
      correlates with both right and left atrial intact fibrinogen level, a systemic
      marker of coagulation.

PMID- 11287892
TI  - Accuracy and cost- and time-effectiveness of digital clip versus videotape
      interpretation of echocardiograms in patients with valvular disease.
AB  - BACKGROUND: Although digital and videotaped images are known to be comparable for
      the evaluation of left ventricular function, their relative accuracy for
      assessment of more complex anatomy is unclear. We sought to compare reading time,
      storage costs, and concordance of video and digital interpretations across
      multiple observers and sites. METHODS: One hundred one patients with valvular (90
      mitral, 48 aortic, 80 tricuspid) disease were selected prospectively, and studies
      were stored according to video and standardized digital protocols. The same
      reviewer interpreted video and digital images independently and at different
      times with the use of a standard report form to evaluate 40 items (e.g., severity
      of stenosis or regurgitation, leaflet thickening, and calcification) as normal or
      mildly, moderately, or severely abnormal. Concordance between modalities was
      expressed at kappa. Major discordance (difference of >1 level of severity) was
      ascribed to the modality that gave the lesser severity. CD-ROM was used to store
      digital data (20:1 lossy compression), and super-VHS videotape was used to store
      video data. The reading time and storage costs for each modality were compared.
      RESULTS: Measured parameters were highly concordant (ejection fraction was 52% +/
      13% by both). Major discordance was rare, and lesser values were reported with
      digital rather than video interpretation in the categories of aortic and mitral
      valve thickening (1% to 2%) and severity of mitral regurgitation (2%). Digital
      reading time was 6.8 +/- 2.4 minutes, 38% shorter than with video (11.0 +/- 3.0,
      range 8 to 22 minutes, P <.001). Compressed digital studies had an average size
      of 60 +/- 14 megabytes (range 26 to 96 megabytes). Storage cost for video was
      A$0.62 per patient (18 studies per tape, total cost A$11.20), compared with
      A$0.31 per patient for digital storage (8 studies per CD-ROM, total cost A$2.50).
      CONCLUSION: Digital and video interpretation were highly concordant; in the few
      cases of major discordance, the digital scores were lower, perhaps reflecting
      undersampling. Use of additional views and longer clips may be indicated to
      minimize discordance with video in patients with complex problems. Digital
      interpretation offers a significant reduction in reading times and the cost of
      archiving.

PMID- 11287893
TI  - Hydatid cyst of the heart as a rare cause of embolization: report of 5 cases and
      review of published reports.
AB  - Cardiac hydatid cyst is seen infrequently, even in regions where hydatid cysts
      are endemic. We report 5 cases of cardiac hydatid cysts, which were diagnosed
      after an embolic event.

PMID- 11287894
TI  - Cleft posterior mitral valve leaflet associated with counterclockwise papillary
      muscle malrotation.
AB  - Isolated clefting of the posterior mitral valve leaflet is an uncommon congenital
      malformation. We report a case of cleft posterior mitral valve leaflet with
      counterclockwise papillary muscle malrotation. Similar abnormalities in papillary
      muscle position have been described in association with atrioventricular septal
      defect but have not been previously reported accompanying isolated clefting of
      the posterior mitral valve leaflet.

PMID- 11287895
TI  - Recurrent pulmonary embolism originating from right atrial myxoma.
AB  - The use of transesophageal echocardiography is a useful adjunct to transthoracic
      echocardiography in the diagnosis and management of right atrial tumors in
      patients who are thought to have idiopathic recurrent pulmonary embolism,
      especially with suboptimal transthoracic echocardiography studies. We describe a
      30-year-old woman with a history of recurrent pulmonary embolism who was admitted
      for investigation of pleuritic chest pain in whom transesophageal
      echocardiography played a critical role in the diagnosis and management.

PMID- 11287896
TI  - Echocardiographic detection and long-term outcome of coronary artery-left
      ventricle fistula after septal myectomy in hypertrophic obstructive
      cardiomyopathy.
AB  - We describe a 51-year-old woman with an acquired coronary fistula to the left
      ventricle. Reports in the literature about acquired coronary fistulas to the left
      ventricle are scarce. In this patient, the fistula developed after septal
      myectomy for hypertrophic obstructive cardiomyopathy. Transesophageal echo
      cardiography may be the preferred method to diagnose and evaluate these fistulas.
      Moreover, in contrast to fistulas to the right ventricle, conservative management
      carried a good prognosis in this patient.

PMID- 11287897
TI  - Apical hypertrophic cardiomyopathy: bedside diagnosis by intravenous contrast
      echocardiography.
AB  - Apical cardiomyopathy is rare in the West. The characteristic appearance on left
      ventriculography has been used to confirm the diagnosis of this condition;
      transthoracic echocardiography can also be useful in this regard. However, apical
      artifacts may obscure the typical appearance during echocardiography, and
      although the advent of tissue harmonic echocardiography has resulted in improved
      image quality, the technique still may be inadequate in the establishment of a
      diagnosis. We hypothesized that contrast echocardiography, which improves
      endocardial border delineation, may be the technique of choice for the diagnosis
      of apical hypertrophic cardiomyopathy. We report the case of a 40-year-old woman
      with Down syndrome who had chest pain. The electrocardiogram showed T-wave
      changes in the lateral precordial leads, but cardiac enzymes were normal. Tissue
      harmonic echocardiography showed apical akinesia. Intravenous contrast
      echocardiography, however, revealed typical features of hypertrophic apical
      cardiomyopathy. Thus contrast echocardiography may be used to establish the
      diagnosis of this condition.

PMID- 11287898
TI  - Severe intermittent intraprosthetic regurgitation after mitral valve replacement
      with subvalvular preservation.
AB  - Preservation of the subvalvular apparatus during mitral valve replacement
      preserves left ventricular function and improves long-term survival.
      Complications of subvalvular preservation include left ventricular outflow tract
      obstruction and prosthesis impingement. We report a case of severe intermittent
      intraprosthetic mitral regurgitation detected by transesophageal echocardiography
      after mitral valve replacement by a bileaflet mechanical prosthesis with
      subvalvular preservation. Intravalvular prosthetic valve regurgitation was caused
      by remnants of the subvalvular apparatus, which were shown at reoperation to
      interfere with prosthetic leaflet motion and which were excised. Postoperative
      transesophageal echocardiography showed neither abnormal mitral regurgitation nor
      residual mass. The use of intraoperative transesophageal echocardiography could
      enable the detection of this rare complication.

PMID- 11287900
TI  - Patent ductus arteriosus in elderly patients: clinical and echocardiographic
      features-a case-based review.
AB  - Congenital heart disease in adults is a rapidly growing field, with many operated
      and unoperated infants and children surviving into adulthood. Patent ductus
      arteriosus is an example of a congenital cardiac defect, which may enable
      patients to survive well into adulthood without prior recognition or correction
      before symptoms arise. This case illustrates the clinical and echocardiographic
      manifestations of patent ductus arteriosus with special emphasis on its 2
      dimensional and Doppler findings. Management options for this condition are also
      briefly addressed.

PMID- 11287899
TI  - Right ventricular dysplasia in an asymptomatic young man: an uncommon case with
      biventricular involvement and no known family history.
AB  - A 33-year-old man had cardiomegaly on a routine x-ray examination. He was
      asymptomatic with no history of infarction, syncope, or palpitations. There was
      no family history of congenital heart disease or sudden death. Two-dimensional
      transthoracic echocardiography demonstrated marked enlargement of the right
      atrium and ventricle with severely depressed right and left ventricular function
      that was consistent with right ventricular dysplasia. The patient was treated
      with an angiotensin-converting enzyme inhibitor and did well for 6 months, but
      then developed symptomatic left-sided congestive heart failure. Short-term
      improvement was obtained with intravenous inotropic therapy, but he continued to
      have progressive symptoms of heart failure. Approximately 7 months after his
      initial presentation, the patient underwent orthotopic heart transplantation for
      intractable congestive heart failure. Pathologic examination of the explanted
      heart established the diagnosis of right ventricular dysplasia with left
      ventricular involvement. This is an uncommon presentation of right ventricular
      dysplasia with biventricular involvement and no known family history.

PMID- 11287901
TI  - Re: personal ultrasound imager: abdominal aortic aneurysm screening.

PMID- 11287903
TI  - Achieving a diagnostic contrast-enhanced echocardiogram: a series on contrast
      echocardiography, article 4.

PMID- 11287904
TI  - Gathering the evidence on medical marijuana.

PMID- 11287905
TI  - E-access to science.

PMID- 11287906
TI  - Experts clash over likely impact of cheap AIDS drugs in Africa.

PMID- 11287907
TI  - Farmer fined for growing GM seed.

PMID- 11287908
TI  - Criticism mounts as Bush backs out of Kyoto accord.

PMID- 11287909
TI  - Climate change transforms island ecosystem.

PMID- 11287910
TI  - Fears of cults and kooks push Congress towards cloning ban.

PMID- 11287911
TI  - Bush appoints venture capitalist as technology adviser.

PMID- 11287912
TI  - Madrid quakes as Barcelona shows ambition.

PMID- 11287913
TI  - Primate centre promises insight into ape research.

PMID- 11287915
TI  - Network boost for southeast Europe.

PMID- 11287914
TI  - Ecologists score victory over controversial dyke project.

PMID- 11287916
TI  - Indian rocket fizzles out as test launch fails to fly.

PMID- 11287917
TI  - AIDS vaccine gets off to a promising start.

PMID- 11287918
TI  - Can they rebuild us?

PMID- 11287919
TI  - A tortured tale of supply and demand.

PMID- 11287920
TI  - Breaking the nuclear taboo.

PMID- 11287921
TI  - EU will gain from funding eastern European centres of excellence.

PMID- 11287922
TI  - Spain is a closed culture to foreign researchers.

PMID- 11287923
TI  - Cultures of knowledge.

PMID- 11287929
TI  - Heavenly phenomena.

PMID- 11287930
TI  - Why rename things?

PMID- 11287931
TI  - Climate and amphibian declines.

PMID- 11287932
TI  - Cardiovascular biology. Hearts and bones.

PMID- 11287934
TI  - Materials science. Rapid alloy assessment.

PMID- 11287936
TI  - Physical chemistry. Molecules at the edge.

PMID- 11287935
TI  - Acoustics. In a fly's ear.

PMID- 11287938
TI  - Cell biology. Channelling calcium.

PMID- 11287939
TI  - Global change. Time, money and tradeoffs.

PMID- 11287941
TI  - Enigmatic northern plains of Mars.

PMID- 11287942
TI  - Food-web dynamics. Animal nitrogen swap for plant carbon.

PMID- 11287943
TI  - Power laws. Are hospital waiting lists self-regulating?

PMID- 11287944
TI  - Materials science. The hardest known oxide.
AB  - A material as hard as diamond or cubic boron nitride has yet to be identified,
      but here we report the discovery of a cotunnite-structured titanium oxide which
      represents the hardest oxide known. This is a new polymorph of titanium dioxide,
      where titanium is nine-coordinated to oxygen in the cotunnite (PbCl2) structure.
      The phase is synthesized at pressures above 60 gigapascals (GPa) and temperatures
      above 1,000 K and is one of the least compressible and hardest polycrystalline
      materials to be described.

PMID- 11287945
TI  - Invariant scaling relations across tree-dominated communities.
AB  - Organizing principles are needed to link organismal, community and ecosystem
      attributes across spatial and temporal scales. Here we extend allometric theory
      how attributes of organisms change with variation in their size-and test its
      predictions against worldwide data sets for forest communities by quantifying the
      relationships among tree size-frequency distributions, standing biomass, species
      number and number of individuals per unit area. As predicted, except for the
      highest latitudes, the number of individuals scales as the -2 power of basal stem
      diameter or as the -3/4 power of above-ground biomass. Also as predicted, this
      scaling relationship varies little with species diversity, total standing
      biomass, latitude and geographic sampling area. A simulation model in which
      individuals allocate biomass to leaf, stem and reproduction, and compete for
      space and light obtains features identical to those of a community. In tandem
      with allometric theory, our results indicate that many macroecological features
      of communities may emerge from a few allometric principles operating at the level
      of the individual.

PMID- 11287946
TI  - Stable methane hydrate above 2 GPa and the source of Titan's atmospheric methane.
AB  - Methane hydrate is thought to have been the dominant methane-containing phase in
      the nebula from which Saturn, Uranus, Neptune and their major moons formed. It
      accordingly plays an important role in formation models of Titan, Saturn's
      largest moon. Current understanding assumes that methane hydrate dissociates into
      ice and free methane in the pressure range 1-2 GPa (10-20 kbar), consistent with
      some theoretical and experimental studies. But such pressure-induced dissociation
      would have led to the early loss of methane from Titan's interior to its
      atmosphere, where it would rapidly have been destroyed by photochemical
      processes. This is difficult to reconcile with the observed presence of
      significant amounts of methane in Titan's present atmosphere. Here we report
      neutron and synchrotron X-ray diffraction studies that determine the
      thermodynamic behaviour of methane hydrate at pressures up to 10 GPa. We find
      structural transitions at about 1 and 2 GPa to new hydrate phases which remain
      stable to at least 10 GPa. This implies that the methane in the primordial core
      of Titan remained in stable hydrate phases throughout differentiation, eventually
      forming a layer of methane clathrate approximately 100 km thick within the ice
      mantle. This layer is a plausible source for the continuing replenishment of
      Titan's atmospheric methane.

PMID- 11287947
TI  - A thermodynamic connection to the fragility of glass-forming liquids.
AB  - Although liquids normally crystallize on cooling, there are members of all liquid
      types (including molecular, ionic and metallic) that supercool and then solidify
      at their glass transition temperature, Tg. This continuous solidification process
      exhibits great diversity within each class of liquid-both in the steepness of the
      viscosity-temperature profile, and in the rate at which the excess entropy of the
      liquid over the crystalline phase changes as Tg is approached. However, the
      source of the diversity is unknown. The viscosity and associated relaxation time
      behaviour have been classified between 'strong' and 'fragile' extremes, using Tg
      as a scaling parameter, but attempts to correlate such kinetic properties with
      the thermodynamic behaviour have been controversial. Here we show that the
      kinetic fragility can be correlated with a scaled quantity representing excess
      entropy, using data over the entire fragility range and embracing liquids of all
      classes. The excess entropy used in our correlation contains both configurational
      and vibration-related contributions. In order to reconcile our correlation with
      existing theory and simulations, we propose that variations in the fragility of
      liquids originate in differences between their vibrational heat capacities,
      harmonic and anharmonic, which we interpret in terms of an energy landscape. The
      differences evidently relate to behaviour of low-energy modes near and below the
      boson peak.

PMID- 11287948
TI  - Intermittent dislocation flow in viscoplastic deformation.
AB  - The viscoplastic deformation (creep) of crystalline materials under constant
      stress involves the motion of a large number of interacting dislocations.
      Analytical methods and sophisticated 'dislocation dynamics' simulations have
      proved very effective in the study of dislocation patterning, and have led to
      macroscopic constitutive laws of plastic deformation. Yet, a statistical analysis
      of the dynamics of an assembly of interacting dislocations has not hitherto been
      performed. Here we report acoustic emission measurements on stressed ice single
      crystals, the results of which indicate that dislocations move in a scale-free
      intermittent fashion. This result is confirmed by numerical simulations of a
      model of interacting dislocations that successfully reproduces the main features
      of the experiment. We find that dislocations generate a slowly evolving
      configuration landscape which coexists with rapid collective rearrangements.
      These rearrangements involve a comparatively small fraction of the dislocations
      and lead to an intermittent behaviour of the net plastic response. This basic
      dynamical picture appears to be a generic feature in the deformation of many
      other materials. Moreover, it should provide a framework for discussing
      fundamental aspects of plasticity that goes beyond standard mean-field approaches
      that see plastic deformation as a smooth laminar flow.

PMID- 11287949
TI  - Varied pore organization in mesostructured semiconductors based on the [SnSe4](4
      ) anion.
AB  - Open framework metal chalcogenide solids, with pore sizes in the nano- and
      mesoscale, are of potentially broad technological and fundamental interest in
      research areas ranging from optoelectronics to the physics of quantum
      confinement. Although there have been significant advances in the design and
      synthesis of mesostructured silicas, the construction of their non-oxidic
      analogues still remains a challenge. Here we describe a synthetic strategy that
      allows the preparation of a large class of mesoporous materials based on
      supramolecular assembly of tetrahedral Zintl anions [SnSe4]4- with transition
      metals in the presence of cetylpyridinium (CP) surfactant molecules. These
      mesostructured semiconducting selenide materials are of the general formulae
      (CP)4-2xMxSnSe4 (where 1.0 < x < 1.3; M=Mn, Fe, Co, Zn, Cd, Hg). The resulting
      materials are open framework chalcogenides and form mesophases with uniform pore
      size (with spacings between 35 and 40 A). The pore arrangement depends on the
      synthetic conditions and metal used, and include disordered wormhole, hexagonal
      and even cubic phases. All compounds are medium bandgap semiconductors (varying
      between 1.4 and 2.5 eV). We expect that such semiconducting porous networks could
      be used for optoelectronic, photosynthetic and photocatalytic applications.

PMID- 11287950
TI  - An alternative approach to establishing trade-offs among greenhouse gases.
AB  - The Kyoto Protocol permits countries to meet part of their emission reduction
      obligations by cutting back on gases other than CO2 (ref. 1). This approach
      requires a definition of trade-offs among the radiatively active gases. The
      Intergovernmental Panel on Climate Change has suggested global warming potentials
      for this purpose, which use the accumulated radiative forcing of each gas by a
      set time horizon to establish emission equivalence. But it has been suggested
      that this approach has serious shortcomings: damages or abatement costs are not
      considered and the choice of time horizon for calculating cumulative radiative
      force is critical, but arbitrary. Here we describe an alternative framework for
      determining emission equivalence between radiatively active gases that addresses
      these weaknesses. We focus on limiting temperature change and rate of temperature
      change, but our framework is also applicable to other objectives. For a proposed
      ceiling, we calculate how much one should be willing to pay for emitting an
      additional unit of each gas. The relative prices then determine the trade-off
      between gases at each point in time, taking into account economical as well as
      physical considerations. Our analysis shows that the relative prices are
      sensitive to the lifetime of the gases, the choice of target and the proximity of
      the target, making short-lived gases more expensive to emit as we approach the
      prescribed ceiling.

PMID- 11287951
TI  - Coupled major and trace elements as indicators of the extent of melting in mid
      ocean-ridge peridotites.
AB  - Rocks in the Earth's uppermost sub-oceanic mantle, known as abyssal peridotites,
      have lost variable but generally large amounts of basaltic melt, which
      subsequently forms the oceanic crust. This process preferentially removes from
      the peridotite some major constituents such as aluminium, as well as trace
      elements that are incompatible in mantle minerals (that is, prefer to enter the
      basaltic melt), such as the rare-earth elements. A quantitative understanding of
      this important differentiation process has been hampered by the lack of
      correlation generally observed between major- and trace-element depletions in
      such peridotites. Here we show that the heavy rare-earth elements in abyssal
      clinopyroxenes that are moderately incompatible are highly correlated with the
      Cr/(Cr + Al) ratios of coexisting spinels. This correlation deteriorates only for
      the most highly incompatible elements-probably owing to late metasomatic
      processes. Using electron- and ion-microprobe data from residual abyssal
      peridotites collected on the central Indian ridge, along with previously
      published data, we develop a quantitative melting indicator for mantle residues.
      This procedure should prove useful for relating partial melting in peridotites to
      geodynamic variables such as spreading rate and mantle temperature.

PMID- 11287952
TI  - Complex causes of amphibian population declines.
AB  - Amphibian populations have suffered widespread declines and extinctions in recent
      decades. Although climatic changes, increased exposure to ultraviolet-B (UV-B)
      radiation and increased prevalence of disease have all been implicated at
      particular localities, the importance of global environmental change remains
      unclear. Here we report that pathogen outbreaks in amphibian populations in the
      western USA are linked to climate-induced changes in UV-B exposure. Using long
      term observational data and a field experiment, we examine patterns among
      interannual variability in precipitation, UV-B exposure and infection by a
      pathogenic oomycete, Saprolegnia ferax. Our findings indicate that climate
      induced reductions in water depth at oviposition sites have caused high mortality
      of embryos by increasing their exposure to UV-B radiation and, consequently,
      their vulnerability to infection. Precipitation, and thus water depth/UV-B
      exposure, is strongly linked to El Nino/Southern Oscillation cycles, underscoring
      the role of large-scale climatic patterns involving the tropical Pacific.
      Elevated sea-surface temperatures in this region since the mid-1970s, which have
      affected the climate over much of the world, could be the precursor for pathogen
      mediated amphibian declines in many regions.

PMID- 11287953
TI  - Towards a resolution of the lek paradox.
AB  - Genetic benefits in the shape of 'good genes' have been invoked to explain costly
      female choice in the absence of direct fitness benefits. Little genetic variance
      in fitness traits is expected, however, because directional selection tends to
      drive beneficial alleles to fixation. There seems to be little potential,
      therefore, for female choice to result in genetic benefits, giving rise to the
      'lek paradox'. Nevertheless, evidence shows that genetic variance persists
      despite directional selection and genetic benefits of female choice are
      frequently reported. A theoretical solution to the lek paradox has been proposed
      on the basis of two assumptions: that traits are condition-dependent, and that
      condition shows high genetic variance. The observed genetic variability in sexual
      traits will be accounted for, because a proportion of the genetic variance in
      condition will be captured and expressed in the trait. Here we report results
      from experiments showing that male courtship rate in the dung beetle Onthophagus
      taurus is a condition-dependent trait that is preferred by females. More
      importantly, male condition has high genetic variance and is genetically
      correlated with courtship rate. Our results thereby represent a significant step
      towards a resolution of the lek paradox.

PMID- 11287954
TI  - Hyperacute directional hearing in a microscale auditory system.
AB  - The physics of sound propagation imposes fundamental constraints on sound
      localization: for a given frequency, the smaller the receiver, the smaller the
      available cues. Thus, the creation of nanoscale acoustic microphones with
      directional sensitivity is very difficult. The fly Ormia ochracea possesses an
      unusual 'ear' that largely overcomes these physical constraints; attempts to
      exploit principles derived from O. ochracea for improved hearing aids are now in
      progress. Here we report that O. ochracea can behaviourally localize a salient
      sound source with a precision equal to that of humans. Despite its small size and
      minuscule interaural cues, the fly localizes sound sources to within 2 degrees
      azimuth. As the fly's eardrums are less than 0.5 mm apart, localization cues are
      around 50 ns. Directional information is represented in the auditory system by
      the relative timing of receptor responses in the two ears. Low-jitter, phasic
      receptor responses are pooled to achieve hyperacute timecoding. These results
      demonstrate that nanoscale/microscale directional microphones patterned after O.
      ochracea have the potential for highly accurate directional sensitivity,
      independent of their size. Notably, in the fly itself this performance is
      dependent on a newly discovered set of specific coding strategies employed by the
      nervous system.

PMID- 11287955
TI  - Motion direction, speed and orientation in binocular matching.
AB  - The spatial differences between the images seen by the two eyes, called binocular
      disparities, can be used to recover the volumetric (three-dimensional) aspects of
      a scene. The computation of disparity depends upon the correct identification of
      corresponding features in the two images. Understanding what image features are
      used by the brain to solve this matching problem is one of the main issues in
      stereoscopic vision. Many cortical neurons in visual areas V1 (ref. 2), MT (refs
      3, 4) and MST (refs 5, 6) that are tuned to binocular disparity are also tuned to
      orientation, motion direction and speed. Although psychophysical work has shown
      that motion direction can facilitate binocular matching, the psychophysical
      literature on the role of orientation is mixed, and it has been argued that speed
      differences are ineffective in aiding correspondence. Here we use a different
      psychophysical paradigm to show that the visual system uses similarities in
      orientation, motion direction and speed to achieve binocular correspondence.
      These results indicate that cells that multiplex orientation, motion direction,
      speed and binocular disparity may help to solve the binocular matching problem.

PMID- 11287956
TI  - The homeobox gene lim-6 is required for distinct chemosensory representations in
      C. elegans.
AB  - The ability to discriminate between different chemical stimuli is crucial for
      food detection, spatial orientation and other adaptive behaviours in animals. In
      the nematode Caenorhabditis elegans, spatial orientation in gradients of soluble
      chemoattractants (chemotaxis) is controlled mainly by a single pair of
      chemosensory neurons. These two neurons, ASEL and ASER, are left-right homologues
      in terms of the disposition of their somata and processes, morphology of
      specialized sensory endings, synaptic partners and expression profile of many
      genes. However, recent gene-expression studies have revealed unexpected
      asymmetries between ASEL and ASER. ASEL expresses the putative receptor guanylyl
      cyclase genes gcy-6 and gcy-7, whereas ASER expresses gcy-5 (ref. 4). In
      addition, only ASEL expresses the homeobox gene lim-6, an orthologue of the human
      LMX1 subfamily of homeobox genes. Here we show, using laser ablation of neurons
      and whole-cell patch-clamp electrophysiology, that the asymmetries between ASEL
      and ASER extend to the functional level. ASEL is primarily sensitive to sodium,
      whereas ASER is primarily sensitive to chloride and potassium. Furthermore, we
      find that lim-6 is required for this functional asymmetry and for the ability to
      distinguish sodium from chloride. Thus, a homeobox gene increases the
      representational capacity of the nervous system by establishing asymmetric
      functions in a bilaterally symmetrical neuron pair.

PMID- 11287957
TI  - C. elegans odour discrimination requires asymmetric diversity in olfactory
      neurons.
AB  - Caenorhabditis elegans senses at least five attractive odours with a single pair
      of olfactory neurons, AWC, but can distinguish among these odours in behavioural
      assays. The two AWC neurons are structurally and functionally similar, but the G
      protein-coupled receptor STR-2 is randomly expressed in either the left or the
      right AWC neuron, never in both. Here we describe the isolation of a mutant,
      ky542, with specific defects in odour discrimination and odour chemotaxis. ky542
      is an allele of nsy-1, a neuronal symmetry, or Nsy, mutant in which STR-2 is
      expressed in both AWC neurons. Other Nsy mutants exhibit discrimination and
      olfactory defects like those of nsy-1 mutants. Laser ablation of the AWC neuron
      that does not express STR-2 (AWCOFF) recapitulates the behavioural phenotype of
      Nsy mutants, whereas laser ablation of the STR-2-expressing AWC neuron (AWCON)
      causes different chemotaxis defects. We propose that odour discrimination can be
      achieved by segregating the detection of different odours into distinct olfactory
      neurons or into unique combinations of olfactory neurons.

PMID- 11287958
TI  - Bone marrow cells regenerate infarcted myocardium.
AB  - Myocardial infarction leads to loss of tissue and impairment of cardiac
      performance. The remaining myocytes are unable to reconstitute the necrotic
      tissue, and the post-infarcted heart deteriorates with time. Injury to a target
      organ is sensed by distant stem cells, which migrate to the site of damage and
      undergo alternate stem cell differentiation; these events promote structural and
      functional repair. This high degree of stem cell plasticity prompted us to test
      whether dead myocardium could be restored by transplanting bone marrow cells in
      infarcted mice. We sorted lineage-negative (Lin-) bone marrow cells from
      transgenic mice expressing enhanced green fluorescent protein by fluorescence
      activated cell sorting on the basis of c-kit expression. Shortly after coronary
      ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the
      infarct. Here we report that newly formed myocardium occupied 68% of the
      infarcted portion of the ventricle 9 days after transplanting the bone marrow
      cells. The developing tissue comprised proliferating myocytes and vascular
      structures. Our studies indicate that locally delivered bone marrow cells can
      generate de novo myocardium, ameliorating the outcome of coronary artery disease.

PMID- 11287959
TI  - CaT1 manifests the pore properties of the calcium-release-activated calcium
      channel.
AB  - The calcium-release-activated Ca2+channel, ICRAC, is a highly Ca2+-selective ion
      channel that is activated on depletion of either intracellular Ca2+ levels or
      intracellular Ca2+ stores. The unique gating of ICRAC has made it a favourite
      target of investigation for new signal transduction mechanisms; however, without
      molecular identification of the channel protein, such studies have been
      inconclusive. Here we show that the protein CaT1 (ref. 4), which has six membrane
      spanning domains, exhibits the unique biophysical properties of ICRAC when
      expressed in mammalian cells. Like ICRAC, expressed CaT1 protein is Ca2+
      selective, activated by a reduction in intracellular Ca2+ concentration, and
      inactivated by higher intracellular concentrations of Ca2+. The channel is
      indistinguishable from ICRAC in the following features: sequence of selectivity
      to divalent cations; an anomalous mole fraction effect; whole-cell current
      kinetics; block by lanthanum; loss of selectivity in the absence of divalent
      cations; and single-channel conductance to Na+ in divalent-ion-free conditions.
      CaT1 is activated by both passive and active depletion of calcium stores. We
      propose that CaT1 comprises all or part of the ICRAC pore.

PMID- 11287960
TI  - IKKalpha controls formation of the epidermis independently of NF-kappaB.
AB  - The IKKalpha and IKKbeta catalytic subunits of IkappaB kinase (IKK) share 51%
      amino-acid identity and similar biochemical activities: they both phosphorylate
      IkappaB proteins at serines that trigger their degradation. IKKalpha and IKKbeta
      differ, however, in their physiological functions. IKKbeta and the IKKgamma/NEMO
      regulatory subunit are required for activating NF-kappaB by pro-inflammatory
      stimuli and preventing apoptosis induced by tumour necrosis factor-alpha (refs
      5,6,7,8,9,10,11). IKKalpha is dispensable for these functions, but is essential
      for developing the epidermis and its derivatives. The mammalian epidermis is
      composed of the basal, spinous, granular and cornified layers. Only basal
      keratinocytes can proliferate and give rise to differentiated derivatives, which
      on full maturation undergo enucleation to generate the cornified layer.
      Curiously, keratinocyte-specific inhibition of NF-kappaB, as in Ikkalpha-/- mice,
      results in epidermal thickening but does not block terminal differentiation. It
      has been proposed that the epidermal defect in Ikkalpha-/- mice may be due to the
      failed activation of NF-kappaB. Here we show that the unique function of IKKalpha
      in control of keratinocyte differentiation is not exerted through its IkappaB
      kinase activity or through NF-kappaB. Instead, IKKalpha controls production of a
      soluble factor that induces keratinocyte differentiation.

PMID- 11287968
TI  - US structural genomics effort needs physicists for success.

PMID- 11287961
TI  - Functional proteins from a random-sequence library.
AB  - Functional primordial proteins presumably originated from random sequences, but
      it is not known how frequently functional, or even folded, proteins occur in
      collections of random sequences. Here we have used in vitro selection of
      messenger RNA displayed proteins, in which each protein is covalently linked
      through its carboxy terminus to the 3' end of its encoding mRNA, to sample a
      large number of distinct random sequences. Starting from a library of 6 x 1012
      proteins each containing 80 contiguous random amino acids, we selected functional
      proteins by enriching for those that bind to ATP. This selection yielded four new
      ATP-binding proteins that appear to be unrelated to each other or to anything
      found in the current databases of biological proteins. The frequency of
      occurrence of functional proteins in random-sequence libraries appears to be
      similar to that observed for equivalent RNA libraries.

PMID- 11287970
TI  - Staffing shortage threatens Japan's structural genomics.

PMID- 11287972
TI  - Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in
      chronic myeloid leukemia.
AB  - BACKGROUND: BCR-ABL is a constitutively activated tyrosine kinase that causes
      chronic myeloid leukemia (CML). Since tyrosine kinase activity is essential to
      the transforming function of BCR-ABL, an inhibitor of the kinase could be an
      effective treatment for CML. METHODS: We conducted a phase 1, dose-escalating
      trial of STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR
      ABL tyrosine kinase. STI571 was administered orally to 83 patients with CML in
      the chronic phase in whom treatment with interferon alfa had failed. Patients
      were successively assigned to 1 of 14 doses ranging from 25 to 1000 mg per day.
      RESULTS: Adverse effects of STI571 were minimal; the most common were nausea,
      myalgias, edema, and diarrhea. A maximal tolerated dose was not identified.
      Complete hematologic responses were observed in 53 of 54 patients treated with
      daily doses of 300 mg or more and typically occurred in the first four weeks of
      therapy. Of the 54 patients treated with doses of 300 mg or more, cytogenetic
      responses occurred in 29, including 17 (31 percent of the 54 patients who
      received this dose) with major responses (0 to 35 percent of cells in metaphase
      positive for the Philadelphia chromosome); 7 of these patients had complete
      cytogenetic remissions. CONCLUSIONS: STI571 is well tolerated and has significant
      antileukemic activity in patients with CML in whom treatment with interferon alfa
      had failed. Our results provide evidence of the essential role of BCR-ABL
      tyrosine kinase activity in CML and demonstrate the potential for the development
      of anticancer drugs based on the specific molecular abnormality present in a
      human cancer.

PMID- 11287973
TI  - Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast
      crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the
      Philadelphia chromosome.
AB  - BACKGROUND: BCR-ABL, a constitutively activated tyrosine kinase, is the product
      of the Philadelphia chromosome. This enzyme is present in virtually all cases of
      chronic myeloid leukemia (CML) throughout the course of the disease, and in 20
      percent of cases of acute lymphoblastic leukemia (ALL). On the basis of the
      substantial activity of the inhibitor in patients in the chronic phase, we
      evaluated STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR
      ABL tyrosine kinase, in patients who had CML in blast crisis and in patients with
      ALL who had the Ph chromosome. METHODS: In this dose-escalating pilot study, 58
      patients were treated with STI571; 38 patients had a myeloid blast crisis and 20
      had ALL or a lymphoid blast crisis. Treatment was given orally at daily doses
      ranging from 300 to 1000 mg. RESULTS: Responses occurred in 21 of 38 patients (55
      percent) with a myeloid-blast-crisis phenotype; 4 of these 21 patients had a
      complete hematologic response. Of 20 patients with a lymphoid blast crisis or
      ALL, 14 (70 percent) had a response, including 4 who had complete responses.
      Seven patients with a myeloid blast crisis continue to receive treatment and
      remain in remission from 101 to 349 days after starting the treatment. All but
      one patient with a lymphoid blast crisis or ALL has relapsed. The most frequent
      adverse effects were nausea, vomiting, edema, thrombocytopenia, and neutropenia.
      CONCLUSIONS: The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and
      has substantial activity in the blast crises of CML and in Ph-positive ALL.

PMID- 11287974
TI  - Long-term survival after ablation of the atrioventricular node and implantation
      of a permanent pacemaker in patients with atrial fibrillation.
AB  - BACKGROUND: In patients with atrial fibrillation that is refractory to drug
      therapy, radio-frequency ablation of the atrioventricular node and implantation
      of a permanent pacemaker are an alternative therapeutic approach. The effect of
      this procedure on long-term survival is unknown. METHOD: We studied all patients
      who underwent ablation of the atrioventricular node and implantation of a
      permanent pacemaker at the Mayo Clinic between 1990 and 1998. Observed survival
      was compared with the survival rates in two control populations: age- and sex
      matched members of the Minnesota population between 1970 and 1990 and consecutive
      patients with atrial fibrillation who received drug therapy in 1993. RESULTS: A
      total of 350 patients (mean [+/-SD] age, 68+/-11 years) were studied. During a
      mean of 36+/-26 months of follow-up, 78 patients died. The observed survival rate
      was significantly lower than the expected survival rate based on the general
      Minnesota population (P<0.001). Previous myocardial infarction (P<0.001), a
      history of congestive heart failure (P=0.02), and treatment with cardiac drugs
      after ablation (P=0.03) were independent predictors of death. Observed survival
      among patients without these three risk factors was similar to expected survival
      (P=0.43). None of the 26 patients with lone atrial fibrillation died during
      follow-up (37+/-27 months). The observed survival rate among patients who
      underwent ablation was similar to that among 229 controls with atrial
      fibrillation (mean age, 67+/-12 years) who received drug therapy (P=0.44).
      CONCLUSIONS: In the absence of underlying heart disease, survival among patients
      with atrial fibrillation after ablation of the atrioventricular node is similar
      to expected survival in the general population. Long-term survival is similar for
      patients with atrial fibrillation, whether they receive ablation or drug therapy.
      Control of the ventricular rate by ablation of the atrioventricular node and
      permanent pacing does not adversely affect long-term survival.

PMID- 11287975
TI  - Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic
      gastrointestinal stromal tumor.

PMID- 11287976
TI  - Images in clinical medicine. A medical mystery.

PMID- 11287977
TI  - Complement. First of two parts.

PMID- 11287978
TI  - Atrial fibrillation.

PMID- 11287979
TI  - Clinical problem-solving. Less is more.

PMID- 11287980
TI  - Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia.

PMID- 11287981
TI  - Managed care in transition.

PMID- 11287982
TI  - Conjoined twins--the limits of law at the limits of life.

PMID- 11287983
TI  - Laparoscopic repair of a Morgagni hernia.
AB  - Morgagni hernias are unusual diaphragmatic hernias which usually present in
      adulthood. They have traditionally been repaired through transabdominal or
      transthoracic approaches. The authors present a case of a laparoscopic repair of
      a Morgagni hernia in a 52-year-old female. A tension free repair of the defect
      was accomplished utilizing Goretex (W.L. Gore & Associates, Inc., North Elkton,
      MD) mesh. The patient had an uneventful recovery and is asymptomatic at 6 months
      follow-up. The etiology, diagnosis and traditional surgical approaches to this
      problem are discussed. A technique for laparoscopic repair of a Morgagni hernia
      is described. The literature on the laparoscopic repair of a Morgagni hernia is
      reviewed and different operative techniques are discussed.

PMID- 11287984
TI  - Transhepatic balloon sphincteroplasty for bile duct stones after total
      gastrectomy.
AB  - Previous upper gastrointestinal surgery with the construction of a Roux-en-Y
      jejunal loop may prevent endoscopic access to the second part of the duodenum. We
      report a technique of percutaneous transhepatic balloon sphincteroplasty to
      facilitate the removal of common bile duct (CBD) stones. A 67-year-old woman
      presented with a 1-week history of right upper quadrant abdominal pain and fever,
      deranged liver function tests, and dilated intrahepatic ducts. The patient had
      previously had a total gastrectomy with Roux-en-Y reconstruction for a high-grade
      B-cell lymphoma of the stomach. Peroral endoscopic access to the biliary tree was
      unsuccessful. Percutaneous transhepatic cholangiography confirmed the presence of
      CBD stones. Over a period of 8 weeks, sequential dilatation of the percutaneous
      tract was undertaken. After a further 2 weeks, percutaneous choledochoscopy was
      performed. Several large stones were visualized and then fragmented. The
      choledochoscope would not pass through to the duodenum due to postinflammatory
      stenosis of the papilla, so the papilla was dilated with an endoscopic balloon.
      The remaining fragments were pushed through, and the duct was thoroughly
      irrigated with saline. Repeat cholangiography confirmed a clear CBD. Balloon
      catheter sphincteroplasty and biliary stone extrusion into the duodenum is a
      novel technique that enabled clearance of the CBD in an elderly patient who may
      otherwise have required open surgical exploration.

PMID- 11287985
TI  - Laparoscopic decompression of abdominal compartment syndrome after blunt hepatic
      trauma.
AB  - Abdominal compartment syndrome (ACS) can occur in a variety of surgical
      conditions, particularly those with major life-threatening hemorrhage, massive
      volume resuscitation, prolonged operation times, and coagulopathy. In severely
      traumatized patients, the incidence of ACS is reported to be as high as 14% to
      15% after damage control laparotomies. Although favorable results have been
      achieved with nonsurgical management of adult blunt hepatic trauma, the failure
      rates still range from 0% to 19%. Exploratory laparotomy is considered the
      intervention of choice in patients with blunt hepatic trauma who fail nonsurgical
      treatment. Expedient abdominal decompression currently is the treatment of choice
      after ACS. Oliguria, tachypnea, and tachycardia developed in two blunt hepatic
      trauma patients with grade IV and V injuries while they were receiving
      nonsurgical treatment. The intra-abdominal pressures measured more than 35 and 25
      cm H 2O, respectively. Two patients with grade II and III ACS received
      laparoscopic examination instead of laparotomy. Their ACS was decompressed
      effectively via laparoscopy without any adverse effects. Therefore, we suggest
      that laparoscopy can be used as a safe alternative for the decompression of ACS.

PMID- 11287986
TI  - Laparoscopic unroofing of retroperitoneal lymphoceles after bilateral
      retroperitoneal lymphadenectomy for testicular cancer.
AB  - BACKGROUND: Symptomatic lymphoceles after retroperitoneal lymphadenectomy for
      testicular cancer are a rare complication that can be managed by either a
      computed tomography (CT)-guided subcutaneous aspiration or surgery. One surgical
      method of choice is laparoscopic unroofing. METHODS: One case of two
      retroperitoneal lymphoceles managed by laparoscopy is presented. After successful
      creation of pneumoperitoneum, first trocar insertion, and lysis of adhesions, the
      two lymphoceles were unroofed, and specimens from the wall and fluid were taken.
      RESULTS: Laparoscopic surgery was uneventful, and the patient returned to
      activity and work within 14 days after the operation. No pathologic signs of
      malignancy were discovered during biopsy and cytology investigations. At the 1
      month follow-up assessment, CT scan demonstrated the regression, and 1 year later
      the total absence of the lymphoceles. CONCLUSIONS: After retroperitoneal
      lymphadenectomy for testicular cancer, clinical suspicion should remain high to
      detect and properly treat symptomatic lymphoceles. Large retroperitoneal
      lymphoceles can be treated effectively by unroofing under the safe direct vision
      of the laparoscope.

PMID- 11287987
TI  - Laparoscopically assisted treatment of acute abdomen in systemic lupus
      erythematosus.
AB  - The incidence of abdominal pain in patients with systemic lupus erythematosus
      (SLE) is very high. Most patients do not require surgical treatment (serositis).
      Some cases such as appendicitis, perforated ulcer, cholecystitis or, rarely,
      intestinal infarction are surgical. Differential diagnosis is difficult, partly
      because noninvasive examinations do not provide enough evidence to rule out a
      diagnosis. On the other hand, in patients with SLE who have acute abdomen, it is
      dangerous to delay surgery by attempting conservative therapy. In fact, a better
      survival rate has been associated with early laparotomy. We report a case of
      acute abdomen in a patient affected by SLE, in which the diagnostic problem was
      solved by means of laparoscopy and the treatment was laparoscopically assisted. A
      45-year-old woman with a 25-year history of SLE was admitted with abdominal pain
      and fever. Her physical examination revealed a painful right iliac fossa with
      rebound tenderness. Her WBC count was normal. Abdominal x-ray, ultrasonography,
      paracentesis, and peritoneal lavage did not provide a diagnosis. A diagnostic
      laparoscopy was performed, showing segmentary small bowel necrosis. The incision
      of the umbilical port site was enlarged to allow a small laparatomy, and a small
      bowel resection was performed. The histopathologic finding was "leucocytoclasic
      vasculitis, with infarction of the intestinal wall." The patient recovered
      uneventfully. In conclusion, this case report shows that emergency diagnostic
      laparoscopy is feasible and useful for acute abdomen in SLE. Currently, this
      diagnostic possibility could be considered the technique of choice in these
      cases, partly because, when necessary, it also can allow for mini-invasive
      treatment therapy.

PMID- 11287988
TI  - Delayed recognition of inadvertent gut injury during laparoscopy.
AB  - Bowel injuries, which may occur as a result of the insertion of an insufflation
      needle or trocar, are a rare complication of laparoscopy. They are generally
      recognized either immediately or a few days after the operation. We present a
      case of laparoscopic perforation of the small intestine in a patient who had
      undergone previous pelvic surgery for an ovarian carcinoma. On ultrasound (US),
      the patient had multiple hepatic lesions resembling hepatic metastases. To
      confirm the diagnosis, laparoscopy with guided liver biopsy was performed on the
      grounds that this procedure is regarded as more appropriate than CT- or US-guided
      hepatic biopsy. Veress needle and trocar insertion were performed at a proper
      distance from the abdominal scar. However, the abdominal cavity was not visible
      after the trocar's insertion due to the unexpected presence of adhesions. This
      precluded the continuation of the procedure. In the following days, the patient
      experienced only mild abdominal discomfort. However, 2 weeks after laparoscopy,
      the patient presented signs of peritoneal reaction and underwent laparotomy.
      Adhesion-fixing jejunal loops to the anterior abdominal wall were discovered at
      the site of the trocar puncture. Moreover, two hiatuses of these loops were
      observed and sutured. The follow-up was uneventful. As this case illustrates,
      laparoscopic bowel injuries remain an unpredictable event. Recognition of this
      complication may occur several days after the procedure, as the tamponating
      effect of adhesions on the jejunal hiatus delays the involvement of the
      peritoneum.

PMID- 11287990
TI  - Ultrasound-guided Kopans' needle location and removal of a retained foreign body.
AB  - Penetrating injury with retained foreign body is a common problem. Location of
      the foreign body and surgical excision may be difficult. Ultrasound can be a
      sensitive and cost-effective tool in both the detection and surgical removal of
      retained foreign bodies in soft tissue. We report a case in which ultrasound
      guided needle localization was used for removal of a wooden foreign body

PMID- 11287989
TI  - Clip migration causes choledocholithiasis after laparoscopic cholecystectomy.
AB  - The migration of surgical clips after laparoscopic procedures was first reported
      in 1992, but such instances are extremely rare. We herein demonstrate a case of a
      migrated metal clip, which had been applied originally to the cystic duct, but
      thereafter had moved to the common bile duct. This clip caused
      choledocholithiasis in a patient 1 year after a laparoscopic cholecystectomy. A
      63-year-old man underwent a laparoscopic cholecystectomy. During the operation,
      the inflamed cystic duct was divided accidentally, and three clips were applied
      immediately. The patient complained of upper abdominal pain from postoperative
      day 8. Endoscopic retrograde cholangiography demonstrated bile leakage from the
      cystic duct, but showed no clips or choledochal stones. The patient complained of
      severe upper abdominal and back pain 1 year after the operation. Endoscopic
      retrograde cholangiography showed a metal clip in the common bile duct and
      choledochal stones above the clip. The clip and the cholesterol stones were
      removed using a basket catheter. Three clips applied to the cystic duct should
      have been removed because of the necrosis in the remaining cystic duct.
      Thereafter, the clip may have migrated through the stump of the cystic duct into
      the lower part of the common bile duct. This clip seems to have later caused
      choledocholithiasis resulting from stagnation of the bile flow. Bile leakage
      after an operation seems to increase the risk of clip migration. Regardless of
      the primary lesion, a careful follow-up evaluation is necessary for patients
      demonstrating complications.

PMID- 11287991
TI  - Common bile duct obstruction secondary to a balloon separated from a Fogarty
      vascular embolectomy catheter during laparoscopic cholecystectomy.
AB  - Laparoscopic instrumentation of the common bile duct (CBD) via the transcystic
      route or through direct choledochotomy seems to be safe, but in rare cases,
      complications such as pancreatitis, bile duct damage, and hemorrhage from cystic
      artery may occur. We report an unusual complication with this approach. A 62-year
      old man with gallbladder stones presented with obstructive jaundice, mild
      pancreatitis, and a dilated CBD. He underwent laparoscopic cholecystectomy with
      an intraoperative cholangiogram through the cystic duct. A small stone seen in
      the CBD was removed using a 6-Fr vascular Fogarty catheter. Two days later, he
      became jaundiced again with a rising bilirubin. An endoscopic retrograde
      cholangiogram showed a 1.5-cm round filling defect floating in a dilated CBD. A
      sphincterotomy was performed, and a balloon catheter was inflated proximally and
      pulled down. To our surprise, the filling defect was a crystal clear object,
      which we finally realized was a fully inflated Fogarty catheter balloon. The
      balloon spontaneously deflated while being caught with a basket. Surgeons should
      be aware of this possible complication, and every effort should be made to verify
      that the balloon still is in place after removal of the embolectomy catheter.
      Whether vascular embolectomy catheter balloons are appropriate for stone removal
      or more rigid balloons should be used needs further evaluation.

PMID- 11287992
TI  - Laparoscopic gastrostomy.
AB  - Although percutaneous endoscopic gastrostomy (PEG) has become a common technique
      for the placement of gastrostomy tubes, gastrostomy can be performed via the
      laparoscopic approach with minimal trauma or by using a percutaneous gastrostomy
      kit. In this report, we describe two procedures for laparoscopic gastrostomy
      using standard instruments. Standard laparoscopic techniques are used to create a
      pneumoperitoneum. In the first method, three transparieto-transgastric U stitches
      are placed to surround the site selected for the gastrostomy. A Foley catheter is
      inserted through the abdominal and gastric opening, then tied to the stomach with
      a pursestring suture. Traction on the balloon catheter brings the stomach to the
      anterior abdominal wall, where the three U stitches can be tied. In the second
      method, a 9-cm vascularized isoperistaltic gastric tube is made on the greater
      curvature using an endoscopic linear cutter and preserving the gastro-omental
      vessels. This gastric tube is then brought out through the anterior abdominal
      wall via a trocar orifice, opened, and fixed to the skin as for standard ostomy.
      Laparoscopic gastrostomy is a straightforward procedure that reduces
      postoperative pain and ileus. It obviates the need for a laparotomy while
      creating an adequate gastrostomy. Postoperative recovery is prompt, with rapid
      return of intestinal function and early discharge from the hospital. It not only
      represents an alternative to PEG when this route is not suitable or after failure
      of the procedure, but can also be widely used for patients as a first choice.

PMID- 11287993
TI  - Laparoscopic duodenal diverticulectomy.
AB  - We report a case of successful laparoscopic resection of a diverticulum with
      gastrointestinal bleeding at the third portion of the duodenum. The patient was a
      76-year-old man who suffered from persistent tarry stools. An upper
      gastrointestinal series and endoscopy revealed a large diverticulum with an ulcer
      and blood clots located at the lateral wall of the distal third portion of the
      duodenum. Under general anesthesia, a pneumoperitoneum was created by
      insufflating the abdominal cavity with CO2. There were dense adhesions caused by
      a previous open cholecystectomy. Four trocars were inserted into the peritoneal
      cavity for this procedure. After dissecting and identifying the duodenal
      diverticulum, we performed a diverticulectomy, using an Endo-GIA linear stapler
      at the base of the retracted diverticulum. There were no intra- or postoperative
      complications. The operative time was 180 min. Intraoperative bleeding was
      minimal. Postoperative duodenogram revealed no deformity or stenosis at the
      resected area. The patient was discharged after an uneventful course, and he has
      been doing well with no complaints during the follow-up period.

PMID- 11287994
TI  - Successful laparoscopic removal of a migrated Angelchik prosthesis.
AB  - Implantation of an Angelchik prosthesis has been considered a quick and safe
      procedure for the surgical treatment of gastroesophageal reflux disease. Since
      its introduction in 1979 more than 25,000 have been inserted worldwide. However,
      the use of this device has been largely abandoned because of frequent
      complications and high costs. One of the more serious complications is migration
      of the prosthesis, which usually requires open correction. We recently operated
      on a 49-year-old man with a migrated Angelchik prosthesis. The device, placed 17
      years earlier, had now migrated to the free abdominal cavity causing recurrent
      urinary tract infections and fecal incontinence. The prosthesis was removed
      laparoscopically via three ports in a simple procedure without any blood loss.
      Recovery was uneventful. At this writing, complaints have resolved, and reflux is
      being controlled medically. This case supports the suggestion that Angelchik
      prosthesis-related problems may be solved laparoscopically, even if the device
      was inserted via an open procedure.

PMID- 11287995
TI  - Laparoscopic management of colonoscopic perforations.
AB  - Colonic perforation is a dangerous complication of colonoscopy, both diagnostic
      and therapeutic, and its management has become controversial. The question of
      conservative vs operative treatment is still under debate. Despite the recent
      expansion and wide acceptance of laparoscopy by surgeons, the feasibility of this
      technique as a means of treating abdominal emergencies has also been questioned.
      Of 575 patients admitted to our institution for abdominal emergencies between
      1993 and 1998, 365 were treated via a laparoscopic approach. Two of these
      patients were treated for colonoscopic perforations, one after a diagnostic
      procedure and one after an operative procedure. Our technique employs an open
      umbilical approach with two other trocars introduced in the right iliac fossa and
      left flank. In the first case, a diverticular perforation of the subperitoneal
      rectum was suspected. The abdomen was copiously irrigated with saline solution
      and a drain was left in the pelvis. In the second patient, localized peritonitis
      was found in the left iliac fossa due to a microperforation of the sigmoid colon.
      It was repaired with a single absorbable suture. The postoperative course was
      unremarkable in both cases. In patients with an emergency abdomen due to a
      postcolonoscopy perforation, we consider the laparoscopic approach feasible and
      safe in experienced hands. It allowed us to avoid an unnecessary laparotomy and
      other time-consuming and expensive diagnostic investigations. This approach
      represents an excellent means of managing this type of emergency abdominal
      situation.

PMID- 11287996
TI  - Liver hematoma following endoscopic retrograde cholangiopancreatography (ERCP).
AB  - We report the case of an 81-year-old man who presented with abdominal pain
      following endoscopic retrograde cholangiopancreatography (ERCP) for
      choledocholithiasis. A diagnosis of infected hematoma was made. A CT-guided
      puncture produced bloody matter that grew Citrobacter freundii. A catheter was
      left in place for 3 weeks before the patient could be discharged from hospital.
      We hypothesize that the hepatic parenchyma had been torn by the guide used during
      the ERCP. This case represents the first report of this type of iatrogenic
      injury.

PMID- 11287997
TI  - Endoscopic resection of a pelvic neurogenic tumor through the retroperitoneal
      approach.
AB  - A pelvic neurogenic tumor resected endoscopically through the retroperitoneal
      approach is described. Close examination of a 62-year-old man who complained of
      dull pain in the lower abdomen revealed a tumor on the posterior surface of the
      iliacus muscle. The tumor was extracted endoscopically without the need for a
      laparotomy. This procedure involves a less invasive approach that may be useful
      for benign retroperitoneal pelvic tumors.

PMID- 11287998
TI  - Laparoscopic cholecystectomy and the Peter Pan syndrome.
AB  - We report the case of a patient who experienced hemobilia a few weeks after
      undergoing laparoscopic cholecystectomy (LC). This condition was due to the
      rupture of a pseudo-aneurysm of the right hepatic artery in the common bile duct,
      probably caused by a clip erroneously fired during LC on the lateral right wall
      of the vessel. It also caused the formation of multiple liver abscesses and the
      onset of sepsis. This life-threatening complication led to melena, fever,
      epigastric pain, pancreatitis, liver dysfunction, and severe anemia, requiring
      urgent hospitalization and operation. In the operating theater, the fistula was
      closed, the liver abscesses drained, and a Kehr tube inserted. Thereafter, the
      patient's general condition improved, and she is now well. LC is often considered
      to be the gold standard for the management of symptomatic cholelithiasis.
      However, recent data have undermined that opinion. The apparent advantages
      offered by LC in the short term (less pain, speedier recovery, shorter hospital
      stay, and lower costs) have been overwhelmed by the complications that occur
      during long-term follow-up. When the late downward trend in the bile duct and the
      vascular injury rate are taken into consideration, the learning curve is
      prolonged. Therefore, LC should be regarded as the surgical equivalent of a
      modern Peter Pan-i.e., it is like a young adult who should make definitive steps
      toward becoming an adult but does not succeed in doing so. We report the case of
      a patient who experienced hemobilia a few weeks after undergoing laparoscopic
      cholecystectomy. Based on the facts in this case, we argue that the endoscopic
      procedure still needs to be perfected and cannot yet be considered the gold
      standard for selected cases of gallstone disease.

PMID- 11287999
TI  - The role of laparoscopy in the diagnosis and treatment of intestinal duplication
      in childhood. A report of two cases.
AB  - In children, the diagnostic approach for cystic abdominal tumors (e.g.,
      intestinal duplication) usually includes CT scan, ultrasound (US), and MRI. In
      small children and babies, the diagnosis is often made by laparotomy. We present
      our preliminary experience with laparoscopic-assisted surgery (LAS) in two girls.
      Both children underwent US as the diagnostic approach using imaging techniques.
      If an intraabdominal mass was identified as cystic or solid, the second step was
      diagnostic laparoscopy with LAS. One of the girls, a 9-year-old, had a history of
      appendectomy and abdominal cramps. US revealed a cystic structure in the right
      lower quadrant. Laparoscopy showed an intestinal duplication, which was
      mobilized; a segmental small bowel resection was then performed. The second girl,
      a (6-month-old,) had an antenatal diagnosed cystic mass. A small bowel
      duplication was found laparoscopically, completely mobilized and excised, and
      harvested through a small umbilical incision. The postop course was uneventful.
      In former times, transverse laparotomy and Pfannenstil incision were the most
      common surgical approaches. LAS combines an excellent means of exploration with
      the simultaneous performance of definitive surgery. Perfect cosmetic results can
      be achieved even in children with rare pathology.

PMID- 11288000
TI  - Laparoscopic partial splenectomies for true splenic cysts. A report of two cases.
AB  - The goals of treatment for nonparasitic splenic cyst include elimination of the
      cyst and prevention of recurrence. We treated two cases of true splenic cysts by
      successfully performing partial splenectomies via a laparoscopic approach. Herein
      we describe the surgical technique used and tactical aspects. Laparoscopic
      partial splenectomies can be a definitive treatment for true splenic cysts in
      that they preserve splenic function and prevent recurrence.

PMID- 11288001
TI  - Large hyperplastic polyps of the colon.
AB  - Hyperplastic polyps are the most frequent nonneoplastic lesions of the colon.
      Typically, they are small sessile polyps (5 mm) located in the rectosigmoid area.
      Recently, they have been identified as markers of neoplastic polyps. Herein we
      describe four cases of large (20 mm in size) hyperplastic polyps found at our
      institution over a 9-year period. All four polyps were excised by endoscopic
      polypectomy on an outpatient basis without complications. Two polyps were in the
      right colon; one was pedunculated, none of them was associated with synchronous
      neoplastic polyps or polyposis. Up to now, follow-up in three patients has been
      negative for metachronous polyps. We conclude that a large hyperplastic polyp is
      an unexpected and rare finding, difficult to distinguish, and not related to
      particular colonic sites or synchronous adenomatous lesions. These polyps should
      be removed with a standard technique, and patients need to be followed with
      successive endoscopies.

PMID- 11288002
TI  - Cartilage primum non nocere.

PMID- 11288003
TI  - The healing effects on the biomechanical properties of joint capsular tissue
      treated with Ho:YAG laser: An in vivo rabbit study.
AB  - PURPOSE: The objective of this study was to evaluate the healing response, after
      thermal treatment with a Ho:YAG laser, on the biomechanical properties of
      capsular soft tissue. TYPE OF STUDY: Before and after trial. METHODS: Forty-five
      New Zealand white rabbits were used in this study. A medial peripatellar
      retinacular thermal capsuloplasty using a Ho:YAG laser and a lateral peripatellar
      retinacular release was performed on 1 knee of each rabbit. The contralateral
      knee served as a control and had a lateral release of the retinaculum only. The
      temperature of the medial retinaculum was maintained at 55 degrees C +/- 5
      degrees C during treatment. The medial peripatellar retinaculum was evaluated at
      0, 6, and 12 weeks postoperatively. Tensile testing of the medial retinaculum and
      a biomechanical assessment evaluating the structural and material properties were
      performed. RESULTS: The ultimate load (force) of the medial retinaculum was 70%,
      56%, and 84% of control at 0, 6, and 12 weeks, respectively, after the procedure.
      The stiffness (force/deformation) of the medial retinaculum was 83% of control at
      0 weeks, 54% at 6 weeks, and 85% at 12 weeks. The ultimate stress (force/area) of
      the medial retinaculum also showed a significant reduction at 0 and 6 weeks
      postoperatively, 63% and 62% of control, respectively. By 12 weeks, the ultimate
      stress was 83% of control. CONCLUSIONS: Thermal treatment of the medial
      retinaculum with a Ho:YAG laser results in soft tissue with significantly
      diminished biomechanical properties after treatment. The results of this study
      suggest that a 12-week period of minimal stress on the capsular tissues should
      follow a thermal capsuloplasty procedure.

PMID- 11288004
TI  - Arthroscopic suture tying: A comparison of knot types and suture materials.
AB  - PURPOSE: The purpose of this study was to determine the structural properties of
      3 arthroscopically tied knots using 2 different suture materials: the French
      knot, the Duncan loop knot, and the original Revo knot. TYPE OF STUDY: Cohort
      analytic study. METHODS: The sutures used were No. 1 PDS II, an absorbent
      monofilament, and No. 1 Ethibond (Ethicon, Somerville, NJ), a braided
      nonabsorbent material. The resulting 6 suture-knot combinations were individually
      tested to failure in both open- and closed-loop configurations. RESULTS: The
      French knot showed the greatest strength compared with the Duncan loop and the
      Revo knot with both No. 1 Ethibond and No. 1 PDS II sutures (P <.05). The No. 1
      Ethibond exhibited higher initial stiffness than the No. 1 PDS II for all 3 knot
      types (P <.05). Results were similar for both open and closed-loop
      configurations. Also, the French knot failed predominantly by suture breakage
      instead of knot slippage for both suture materials. CONCLUSIONS: The results of
      this study suggest that, among the suture and knot combinations investigated in
      this study, the arthroscopic repair of musculoskeletal injuries should be
      performed using the French knot and No. 1 Ethibond suture.

PMID- 11288005
TI  - The EndoPearl device increases fixation strength and eliminates construct
      slippage of hamstring tendon grafts with interference screw fixation.
AB  - PURPOSE: The EndoPearl (Linvatec, Largo, FL), a biodegradable device to augment
      the femoral interference screw fixation of hamstring tendon grafts has been
      developed. The first objective of this study was to compare the initial fixation
      strength of quadrupled hamstring tendons and biodegradable interference screw
      fixation with and without the application of the EndoPearl device. The second
      objective was to determine the influence of the EndoPearl device on the fatigue
      behavior under incremental cyclic loading conditions in a simulation of critical
      fixation conditions. TYPE OF STUDY: Biomechanical study. METHODS: Fresh human
      hamstring tendons were harvested and grafts were fixed with biodegradable poly-L
      lactide interference screws. Twenty proximal calf tibias were used to compare the
      initial fixation strength of the study and the control group. In the study group,
      the EndoPearl device was secured to the graft using two No. 5 Ethibond sutures
      (Ethicon, Somerville, NJ). Specimens were loaded until failure in a materials
      testing machine. For cyclic testing, human hamstring tendons and 20 distal
      porcine femurs were used. Critical graft fixation conditions were simulated by
      increasing tunnel diameter 2 mm over the graft diameter. Grafts were loaded
      progressively in increments of 100 N until failure; 100 cycles were applied per
      load increment. RESULTS: Graft fixation with the additional EndoPearl device had
      a significantly higher maximum load to failure (658.9 +/- 118.1 N v 385.9 +/-
      185.6 N, P =.003) and stiffness (41.7 +/- 11 N/mm v 25.7 +/- 8.5 N/mm). Graft
      fixation with the EndoPearl device sustained a significant higher total number of
      cycles (388.5 +/- 125.6) compared with the control group (152.8 +/- 144.9, P
      =.002). CONCLUSIONS: We demonstrated that the augmentation of a hamstring tendon
      graft with the EndoPearl device increases interference screw fixation strength
      significantly. Under dynamic loading conditions, specimens of the study group
      sustained substantially higher loads and a larger number of cycles, which
      indicates a greater resistance to graft slippage. The application of the
      EndoPearl device may also allow for a secure soft-tissue graft fixation with
      interference screws in cases of critical fixation conditions.

PMID- 11288006
TI  - Cyclic loading of rotator cuff repairs: A comparison of bioabsorbable tacks with
      metal suture anchors and transosseous sutures.
AB  - PURPOSE: The purposes of the study were (1) to compare rotator cuff repair
      strengths after cyclic loading of 2 bioabsorbable nonsuture-based tack-type
      anchors, transosseous sutures, and a metal suture-based anchor, and (2) to
      correlate bone mineral density with mode of failure and cycles to failure. We
      hypothesized that specimens with a lower bone density would fail through bone at
      a lower number of cycles independent of the method of cuff fixation. TYPE OF
      STUDY: Ex vivo biomechanical study. METHODS: Standardized full-thickness rotator
      cuff defects were created in 30 fresh-frozen cadaveric shoulders that were
      randomized to 1 of 4 repair groups: transosseous sutures; Mitek Super suture
      anchors (Mitek Surgical Products, Westwood, MA); smooth bioabsorbable 8-mm
      Suretacs (Acufex, Smith & Nephew Endoscopy, Mansfield, MA); or spiked
      bioabsorbable 8-mm Suretacs (Acufex). All repairs were cyclically loaded from 10
      to 180 N; the numbers of cycles to 50% (gap, 5 mm) and 100% (gap, 10 mm) failure
      were recorded. RESULTS: In comparing the repair groups, we found only 1
      significant difference: the number of cycles to 100% failure was significantly
      higher (P <.05) for the smooth bioabsorbable tack than for the transosseous
      suture group. There were no statistically significant (P </=.05) differences in
      bone mineral densities with regard to each specimen's mode of failure.
      CONCLUSIONS: Our results suggested that immediate postoperative fixation provided
      by bioabsorbable tacks was similar to that provided by Mitek anchors and more
      stable than that provided by transosseous sutures. Therefore, the immediate
      postoperative biomechanical strength of bioabsorbable tacks seems comparatively
      adequate for fixation of selected small rotator cuff tears. However, additional
      evaluation in an animal model to examine degradation characteristics and
      sustained strength of repair is recommended before clinical use.

PMID- 11288007
TI  - Contact geometry at the undersurface of the acromion with and without a rotator
      cuff tear.
AB  - PURPOSE: The purpose of this study was to investigate the difference in contact
      geometry at the undersurface of acromion in shoulders with and without a rotator
      cuff (RC) tear. TYPE OF STUDY: Case-control study. METHODS: Forty fresh cadaveric
      shoulders (average age at death, 61 years) without gross osteoarthritic changes
      were divided into the intact RC group (n = 20) and the RC tear group (n = 20).
      Clinical impingement was simulated by compressing the humeral head and the intact
      portion of the RC against the coracoacromial arch with an axial compressive force
      of 25 kg while the humerus was held abducted 20 degrees in the scapular plane.
      The contact pattern between the acromion and the RC was measured with Fuji
      Prescale super low-pressure-sensitive film (Fuji Photo Film Co, Ltd, Tokyo,
      Japan). The imprint image was analyzed using Global Lab image software
      (Automatix, Marlboro, MA). RESULTS: The percentage of the maximum anteroposterior
      dimension of the imprint on Fuji film to the anteroposterior diameter of the
      acromial undersurface was 29% +/- 9% in intact RC shoulders, and 39% +/- 13% in
      shoulders with an RC tear (P >.05). The percentage of the maximum mediolateral
      dimension of the imprint to the mediolateral diameter of the corresponding part
      of the acromial undersurface was 27% +/- 12% in intact RC shoulders, and 48% +/-
      11% in shoulders with an RC tear. This difference was statistically significant
      (P <.005). CONCLUSIONS: The contact geometry of the acromial undersurface with
      the underlying RC in the anteroposterior dimension, which might be related to the
      appearance in supraspinatus outlet view, was not significantly different between
      shoulders with and without an RC tear. These findings suggest that factors other
      than acromial shape play a significant role in the pathogenesis of RC tears. The
      implication regarding the role of acromioplasty remains to be clarified.

PMID- 11288008
TI  - Arthroscopic repair of acute traumatic anterior shoulder dislocation in young
      athletes.
AB  - PURPOSE: To compare the results of arthroscopic repair in acute anterior shoulder
      traumatic dislocation with those of nonoperative treatment. TYPE OF STUDY: A
      prospective nonrandomized study was performed. METHODS: Between August 1989 and
      April 1997, 46 patients were seen after a first episode of traumatic anterior
      shoulder dislocation. The average age was 21 years (range, 17 to 27 years). Most
      dislocations were in rugby players (36 patients). There were 18 patients treated
      by nonoperative methods and 28 patients treated by acute arthroscopic repair; 22
      patients using transglenoid suture and 6 patients with bone anchor suture
      fixation. RESULTS: Of the patients treated nonoperatively, 94.5% suffered a
      redislocation between 4 and 18 months (average, 6 months). In the operative
      group, 96% of the patients (27) obtained excellent results according to the Rowe
      scale. Only 1 patient suffered a redislocation 1 year after surgery. Three
      different types of lesions were found during surgery: group I, capsular tear with
      no labrum lesion (4%); group II, capsular tear with partial labrum detachment
      (32%); and group III, capsular tear and full anterior labrum detachment (64%).
      The average follow-up was 67.4 months (range, 28 to 120). There were no surgical
      complications. CONCLUSIONS: The operative group obtained 96% excellent results,
      but the nonoperative group only obtained 5.5% excellent results, according to the
      Rowe scale. The nonoperative group showed a high incidence of redislocation
      (94.5%) compared with the operative group (4%). Based on the findings of this
      study, we recommend using an arthroscopic evaluation and repair after an initial
      anterior traumatic shoulder dislocation in young athletes.

PMID- 11288009
TI  - Biomechanical evaluation of the origin of the long head of the biceps tendon.
AB  - PURPOSE: Lesions of the superior glenoid labrum extending anterior and posterior
      (SLAP) have recently been recognized as important sources of shoulder pain and
      dysfunction. Among the 4 described types of SLAP lesions, the type II SLAP
      involves detachment of the superior labrum from the bony glenoid and
      destabilization of the origin of the long head of the biceps tendon (LHBT). The
      purpose of this cadaveric biomechanical study was to evaluate the relative
      contribution regarding linear stiffness and displacement under load of the 2
      origins of the LHBT: the superior glenoid labrum and the supraglenoid tubercle
      (the biceps anchor). TYPE OF STUDY: Cadaveric biomechanical study. METHODS: Seven
      pairs of fresh-frozen cadaveric shoulders were dissected free of all soft tissue
      except for the glenoid labrum and LHBT. Tension from 0 to 55 N was applied to the
      LHBT while keeping the tendon perpendicular to the face of the glenoid. Each
      specimen was tested for linear stiffness and biceps tendon displacement in the
      intact state, after releasing 1 of the LHBT origins, and after releasing the
      remaining origin. RESULTS: The average stiffness of the LHBT origin was 103 N/mm.
      Sectioning the anchor alone resulted in a 52% reduction in linear stiffness,
      whereas only detaching the superior glenoid labrum from the 10 o'clock to the 2
      o'clock position resulted in a 15% reduction in linear stiffness. Maximum
      displacement of the biceps tendon origin in the intact state at the 55 N load
      averaged 0.99 mm. With a minimum load applied, displacement changed less than 1
      mm unless both origins were released. CONCLUSIONS: The results indicate that the
      biceps anchor is the primary restraint of the LHBT and that the superior labrum
      is a secondary restraint in regard to linear stiffness. However, disruption of
      both restraints is required to produce the laxity typically seen in a type II
      SLAP lesion.

PMID- 11288010
TI  - A comparison of outcomes at 2 to 6 years after acute and chronic anterior
      cruciate ligament reconstructions using hamstring tendon grafts.
AB  - PURPOSE: To compare short- to intermediate-term outcomes of patients in whom an
      acute or chronic anterior cruciate ligament (ACL) reconstruction was performed
      with a hamstring tendon graft. TYPE OF STUDY: A consecutive case series of
      patients who had 2-incision, arthroscopically assisted ACL reconstructions with a
      triple-strand hamstring tendon graft was retrospectively evaluated. METHODS: A
      total of 120 patients were evaluated at a mean of 44 months. The Tegner Activity
      Scale, individual components of the Cincinnati Knee Rating System, and the
      modified Lysholm Score were administered to all patients. A total of 93 patients
      (78%) returned for examination, instrumented ligament laxity testing,
      radiographs, isokinetic strength testing, and completion of the IKDC Standard
      Knee Ligament Evaluation Form. Data from patients undergoing reconstructions for
      acute and chronic ACL deficiencies were compared. The acute group was defined as
      reconstruction within 6 weeks of injury without recurrent episodes of
      instability. RESULTS: At surgery, significantly more (P <.05) cartilage
      abnormalities and partial medial menisectomies were found in the chronic group.
      At final follow-up, no significant differences (P >.05) were found between the
      acute and chronic groups for instrumented laxity, muscle strength, knee motion,
      or sports activity level. The acute group scored significantly higher (P <.05) on
      the Lysholm scale, Cincinnati Function scale, IKDC subjective assessment, and
      IKDC rating for pain at follow-up. The final IKDC grade resulted in significantly
      more (P =.039) normal knees for the acute group; however, 94.1% of acute and
      92.9% of chronic knees were graded normal or nearly normal. CONCLUSIONS:
      Hamstring tendons are an excellent graft choice for ACL reconstruction in both
      acute and chronic injuries. According to the strict IKDC rating system, greater
      than 90% of all patients can be expected to have a normal or nearly normal knee
      at short- to intermediate-term follow-up; however, the chronic group will have
      fewer patients with a rating of normal.

PMID- 11288011
TI  - Prevention of venous thromboembolism after knee arthroscopy with low-molecular
      weight heparin (reviparin): Results of a randomized controlled trial.
AB  - PURPOSE: Deep venous thrombosis (DVT) is a common, important complication of
      major orthopaedic surgery, particularly knee arthroplasty. Knee arthroscopy is
      increasingly performed on an outpatient basis. Few reports have elucidated the
      incidence of venous thromboembolism (VTE) in patients undergoing arthroscopic
      surgery receiving no prophylaxis. The objective of the present trial was to
      evaluate the risk of VTE in those patients and to determine efficacy and safety
      of a low-molecular weight heparin (LMWH) in preventing VTE. TYPE OF STUDY: This
      is the first controlled randomized trial using objective diagnostic methods with
      blinded outcome assessment to reveal the incidence of VTE in outpatient
      arthroscopy and determine efficacy and safety of a LMWH (reviparin sodium) in
      preventing VTE in these patients. METHODS: There were 262 patients undergoing
      elective knee arthroscopy prospectively randomized to receive either no treatment
      or reviparin once daily subcutaneously for 7 to 10 days. The blindly assessed
      primary outcome measure was the incidence of DVT detected by compression color
      coded sonography. Both groups were comparable with regard to demographics and
      baseline characteristics. RESULTS: 239 patients were evaluable (122 no treatment,
      117 receiving LMWH). 6 DVT were detected - 5 in the control group (5/117 - 4.1%)
      and only one in the active treatment group (1/116 - 0.85%). This particular
      patient had a low level of protein C and a subnormal level of protein S. The odds
      ratio of 4.95 approximates a relative risk reduction of about 80%. Treatment with
      reviparin was safe and well tolerated. There was no major bleeding, four patients
      with minor bleedings. One patient had a transitory fall in platelet count below
      100 giga-particles/L without any clinical symptoms. CONCLUSIONS: Patients
      undergoing knee arthroscopy have a moderate risk of VTE and effective prophylaxis
      can be achieved with LMWH (reviparin).

PMID- 11288012
TI  - Pseudoaneurysm as a complication of ankle arthroscopy.
AB  - We describe a case of pseudoaneurysm of the anterior tibial artery as a
      complication after arthroscopic ankle synovectomy, in which standard
      anterolateral and anteromedial portals were used. Pseudoaneurysm has been
      previously reported as a complication in ankle arthroscopy with the use of the
      anterocentral portal. Previously described anatomic variations of the tibial
      artery and its close relationship with the anterior ankle capsule may complicate
      arthroscopic surgery, especially when aggressive synovectomy is performed.
      Anterior tibial artery aneurysm is a rare complication of ankle arthroscopy, but
      its potential catastrophic sequelae must not be underestimated.

PMID- 11288014
TI  - Osseous metaplasia as a cause of loss of extension after anterior cruciate
      ligament reconstruction.
AB  - We report a case of osseous metaplasia of an autologous anterior cruciate
      ligament (ACL) reconstruction that was implicated in blocking extension of the
      knee. Nonoperative treatment was unsuccessful. Arthroscopic excision of the ACL
      and osseous metaplasia abolished the fixed flexion deformity. The osseous
      metaplasia was an additional factor in causing the block to extension along with
      an anteriorly placed femoral tunnel, raising the question that nonisometry of the
      graft may be involved in the pathogenesis of the osseous metaplasia.

PMID- 11288013
TI  - A case of superficial peroneal nerve injury during ankle arthroscopy.
AB  - We report a case of superficial peroneal nerve (SPN) injury caused by ankle
      arthroscopy. A 20-year-old woman underwent arthroscopy on her right ankle because
      of chronic ankle pain after a sprain. After arthroscopy, the patient complained
      of pain on the dorsum of her right foot and felt a radiating pain from the
      anterolateral portal to the dorsomedial aspect of her foot. Eight months after
      arthroscopy, we found that a neuroma had developed on the intermediate dorsal
      cutaneous nerve, and performed neurolysis of the SPN. Her symptoms gradually
      decreased after surgery, and had disappeared by 45 months. To avoid such an
      injury of the SPN, the safest placement of the anterolateral portal is necessary
      and is, according to our previous anatomic study, 2 mm lateral to the peroneus
      tertius tendon.

PMID- 11288015
TI  - Reflex extension loss after anterior cruciate ligament reconstruction due to
      femoral "high noon" graft placement.
AB  - We describe a rare case of a painful reflex extension loss due to femoral
      malplacement of an anterior cruciate ligament (ACL) graft in a female high-level
      athlete. The graft was placed on the femoral site in the "high noon" position
      combined with a slight medial tibial tunnel placement. The resulting anterior
      posterior cruciate ligament impingement near extension caused a persistent
      functional extension deficit of 20 degrees. Under anesthesia, the extension loss
      diminished, and thus it was hypothesized that the ACL-PCL impingement during
      extension activates a proprioceptive reflex leading to a functional extension
      loss while the patient is awake. After sacrifice of the graft and subsequent
      replacement of the ACL, full range of motion was achieved within 2 months. After
      a 3-year postinjury history of 3 arthroscopies and 2 ACL reconstructions, the
      athlete reached her preinjury activity level again. This rare cause of a reflex
      extension loss due to femoral high noon graft placement has not been described
      previously and should be included as a differential diagnosis when evaluating
      patients with an extension deficit after ACL reconstruction.

PMID- 11288016
TI  - Pigmented villonodular synovitis following arthroscopic laser surgery of the
      knee.
AB  - We report a case of a nodular variant of pigmented villonodular synovitis of the
      knee that developed after an arthroscopic lateral release of the synovium by
      laser for an unrelated condition. This case, the first reported case of pigmented
      villonodular synovitis following laser treatment, lends weight to the etiological
      association with the pathological processes of the response to trauma.

PMID- 11288017
TI  - Atraumatic hemarthrosis caused by a large mediopatellar plica.
AB  - Hemarthrosis of the knee has various etiologies and is classified into atraumatic
      or post-traumatic. Among atraumatic factors, hemarthrosis due to synovial plica
      is extremely rare. We report a case of atraumatic hemarthrosis caused by the
      mediopatellar plica. A 21-year-old male truck driver was referred to our
      hospital, because of swelling and pain of the right knee without history of
      trauma. Bloody synovial fluid was aspirated by arthrocentesis. However, his
      symptoms recurred and persisted. The range of motion was normal, but the patient
      complained of anteromedial knee pain during maximum flexion. Routine biochemical
      analyses were within normal limits. Plain radiographs were normal. Magnetic
      resonance imaging (MRI) of the knee showed the hypertrophic mediopatellar plica
      and an irregular signal of the infrapatellar fat pad. Arthroscopy revealed a
      voluminous mediopatellar plica trapped between the patella and the medial femoral
      condyle. It attached to the center of the infrapatellar fat pad, the so-called
      tongue. When the tourniquet was released, fresh bleeding was observed from the
      region between the mediopatellar plica and the tongue. Because that region was
      considered to be the cause of the hemarthrosis, the mediopatellar plica and the
      tongue were excised. A histologic examination of the tongue showed evidence of
      bleeding with nonspecific synovitis. After the procedure, the patient was
      asymptomatic and there were no clinical signs of recurrence.

PMID- 11288018
TI  - Combined fracture of the talus: Arthroscopic treatment.
AB  - The purpose of this article is to report the treatment and short-term results of
      a combined fracture of the talus treated arthroscopically. A 29-year-old man
      sustained an anterolateral osteochondral grade III fracture of the talus dome
      associated with a coronal fracture of the body of the talus. This injury was
      reduced and fixed arthroscopically using cannulated screws. The patient returned
      to his daily style of living after 3 months time. One year later, the patient
      remains asymptomatic. Radiography showed neither signs of osteonecrosis nor
      osteoarthritis of the talus at the 1-year follow-up. Therefore, arthroscopic
      surgery could be an alternative treatment for this kind of talus fracture.

PMID- 11288020
TI  - A new technique of arthroscopic capsular shift in anterior shoulder instability.
AB  - We describe a new arthroscopic technique to reinforce the torn inferior
      glenohumeral ligament (IGHL) and the elongated capsule to the glenoid rim. The
      arthroscope is inserted over the superior portal and, after the insertion of a
      suture anchor, both limbs are pulled out over the posterior portal. The IGHL is
      grasped and pulled upward onto the glenoid rim using a suture retriever clamp
      inserted over the posterior portal. A 45 degrees curved blunt clamp (Sidewinder;
      Arthrex, Naples, FL) coming from the anterior penetrates the IGHL, and 1 end of
      the suture limb is given into the branches of the clamp and pulled out
      anteriorly. After a second perforation of the capsule, a horizontal suture
      creating a neolabrum can be placed. This technique allows a suitable
      reinforcement of the capsule without intraoperative complications. In cases of
      capsular elongation, especially a torn IGHL, the capsular instability can be
      addressed by the described Sidewinder technique. More sophisticated arthroscopic
      techniques such as this will increase the indication for arthroscopic shoulder
      stabilization.

PMID- 11288019
TI  - Arthroscopic reattachment of an avulsion fracture of the tibial insertion of the
      posterior cruciate ligament.
AB  - We describe an arthroscopic technique for the treatment of isolated avulsion
      fracture of the tibial insertion of the posterior cruciate ligament. Arthroscopic
      examination of the injured joint permits visualization of the intra-articular
      structures and lavage of the joint. Such an approach reduces the risk of injury
      to the posterior neurovascular complex. K-wire fixation affords anatomic and
      rigid internal fixation while minimizing the potential for further damage to the
      osseous fragment.

PMID- 11288021
TI  - Complete arthroscopic examination of the long head of the biceps tendon.
AB  - We describe an arthroscopic technique that allows complete examination of the
      long head of the biceps tendon. Important additional information during
      arthroscopic examination of the shoulder can be obtained by including inspection
      of the intertubercular portion of the tendon. Failure to inspect this portion of
      the tendon may lead to an unsuccessful and frustrating postoperative course for
      both the patient and physician.

PMID- 11288022
TI  - Regarding the article by F. Alan Barber, M.D., "Flipped Patellar Tendon Autograft
      Anterior Cruciate Ligament Reconstruction" (Arthroscopy 2000;16:483-490).

PMID- 11288024
TI  - Posterior cruciate ligament reconstruction (double bundle) using anterior
      tibialis tendon allograft.
AB  - Posterior cruciate ligament (PCL) reconstruction using a double-bundle technique
      has been described. However, reconstruction with a cryopreserved anterior
      tibialis tendon allograft and bioabsorbable fixation has not been described. The
      purpose of this article is to present this surgical technique with discussion and
      rationale for its indication and use in patients with PCL-deficient knees.

PMID- 11288025
TI  - Arthroscopic reduction and fixation of osteochondral fracture of the patellar
      ridge.
AB  - A method of arthroscopic reduction and anterograde fixation of osteochondral
      fracture of the patella ridge is described. This type of fracture was previously
      treated through arthrotomy. An arthroscopic approach is possible using
      manipulation of the patella in a loosened medial retinaculum. This method was
      used in a 14-year-old patient with an osteochondral fracture following the
      dislocation of the patella.

PMID- 11288026
TI  - Tibial plateau fracture after arthroscopic anterior cruciate ligament
      reconstruction.
AB  - Complications have been described with each technique for reconstruction of the
      anterior cruciate ligament (ACL) in the knee, both open and arthroscopically
      assisted. The authors describe a case of tibial plateau fracture occurring 7
      months after an ACL reconstruction using the half tunnel technique. The fracture
      occurred at the tibial fixation site and required open reduction with internal
      fixation. To our knowledge, only 2 cases of proximal tibial fracture after
      patellar tendon autograft ACL reconstruction have been previously reported. The
      authors hypothesize that patellar tendon harvesting with bone blocks and
      transosseous tibial tunnel can produce a "stress riser" effect and somehow act
      synergistically to create decreased strength at the level of proximal tibial
      metaphysis.

PMID- 11288027
TI  - Simultaneous bilateral anterior cruciate ligament ruptures in a cheerleader.
AB  - The anterior cruciate ligament (ACL) is frequently injured during both
      recreational and competitive activity. It is common to see patients who have
      ruptured both ACLs at different times. Intercondylar notch width, notch
      morphology, gender, and family history have all been implicated as factors that
      may predispose an individual to contralateral ACL rupture following unilateral
      injury. Simultaneous bilateral ACL rupture is a rare occurrence. Only 1 other
      case has previously been reported. We report the case of a 17-year-old high
      school cheerleader who sustained simultaneous bilateral ACL ruptures. Some of the
      commonly implicated risk factors for ACL rupture are examined and a review of the
      literature is also presented.

PMID- 11288028
TI  - Preliminary report: effect of adrenal androgen and estrogen on bone maturation
      and bone mineral density.
AB  - To clarify the independent physiological roles of adrenal androgen and estrogen
      on bone growth, we compared the lumbar spine bone mineral density (BMD) in
      prepubertal girls with virilizing congenital adrenal hyperplasia (CAH) (n = 17)
      and girls with central precocious puberty (CPP) (n = 18). When BMD was analyzed
      according to chronologic age, no significant differences were found between CPP
      and CAH patients. However, when adjusted to bone age, BMD was statistically
      higher in CAH than in CPP subjects. This finding suggests that adrenal androgen,
      as well as estrogen, plays an important role in increasing BMD. Adrenal androgen
      may act on bone not only as androgen, but as estrogen after having been
      metabolized into an aromatized bone-active compound in peripheral tissues, such
      as bone and fat. Therefore, adrenal androgen may have a more important role in
      increasing BMD than previously realized.

PMID- 11288029
TI  - Preliminary report: skeletal muscle cell lipid and oxygen supply.
AB  - In a group of 12 normal-weight, normotensive, nondiabetic adult females, the
      intramyocellular lipid (IMCL) to creatine ratio of the soleus muscle was
      determined using localized (1)H-magnetic resonance spectroscopy ((1)H-MRS) and
      related to skeletal muscle blood (and oxygen) supply (as assessed by near
      infrared spectroscopy [NIRS] of the forearm). A significant positive association
      was found between IMCL content and reoxygenation rate of forearm muscle
      hemoglobin (Hb) after 1 minute of ischemic exercise (r = .70, P = .01). The
      relative efficiency of skeletal muscle oxygen supply may be a determining factor
      of IMCL content in skeletal muscle.

PMID- 11288030
TI  - Opioid dysregulation after biliopancreatic diversion: effect of naloxone on
      preprandial and postprandial growth hormone (GH)-releasing hormone-induced GH
      release in surgically induced weight loss.
AB  - Previously, we have shown that in the opposite extremes of nutritional status
      (obesity and anorexia nervosa [AN]), the growth hormone (GH) response to GH
      releasing hormone (GHRH) is not inhibited by the ingestion of a normal 800-kcal
      meal at noon. In obese subjects, GHRH-induced GH release is significantly
      increased (known as the "paradoxical response"). An opiate antagonist infusion
      (naloxone [NAL]) inhibited this postprandial meal-induced augmenting effect in
      obese subjects, suggesting opioid involvement in the paradoxical response. The
      paradoxical postprandial GH release persisted in obese subjects, who after
      biliopancreatic diversion (BPD) experienced a reduction in body weight, despite
      the elevation of fasting GH levels. We therefore tested a group of patients,
      before and after BPD, composed of 10 females, aged 23 to 54 years, who after
      surgery had experienced a significant reduction in body weight (mean body mass
      index [BMI], 25.78 +/- 1.01 kg/mg v 44.68 +/- 1.73 kg/mg). The subjects were
      studied 16 to 24 months after operation, in a phase of stabilized body weight.
      They underwent, in randomized order, the following tests: GHRH (1 microg/kg as an
      intravenous [IV] bolus) at 1:00 PM, in the fasting state; GHRH (1 microg/kg) at
      1:00 PM, 45 minutes after a standard 800-kcal meal consumed between noon and
      12:15 PM; and fasting state and postprandial GHRH (1 microg/kg) during NAL
      infusion (1.6 mg/h x 2.5 h, starting at noon). We found that NAL inhibited the
      paradoxical postprandial GH increase only in pre-BPD subjects (GH area under the
      concentration time curve [AUC] in microg/L/90 min)-before meal: after GHRH 237.54
      +/- 62.28, after NAL + GHRH 699.2 +/- 271.57; after meal: after GHRH 575.46 +/-
      109.68, after NAL + GHRH 156.17 +/- 24.96. On the other hand, NAL failed to have
      significant effects in post-BPD subjects (GH AUC in microg/L/90 min)-before meal:
      after GHRH 871.11 +/- 256.38, after NAL + GHRH 449.19 +/- 119.13; after meal:
      after GHRH 1,981.54 +/- 319.92, after NAL + GHRH 1,665.91 +/- 315.4. It could be
      hypothesized that the opioid system is radically modified by the surgical
      procedure, and that opioids are not the only mediators in the paradoxical
      response, which persists after BPD, despite the reversion of the hyposecretory GH
      state, which is a characteristic of obese subjects.

PMID- 11288031
TI  - Effects of insulin on glucose uptake and leg blood flow in patients with sickle
      cell disease and normal subjects.
AB  - The hemodynamic concept of insulin resistance assumes that vasodilatory effects
      of insulin determine glucose uptake. Sickle cell disease (SCD) is characterized
      by microangiopathy and microvascular occlusion. Therefore, we hypothesized that
      patients with SCD have a reduced insulin-mediated glucose uptake. In 8 patients
      with SCD and 8 matched normal controls, we studied the effects of a 4-hour
      insulin infusion (50 mU/kg/h) on glucose uptake and leg blood flow (LBF) using
      the euglycemic clamp technique and venous occlusion plethysmography. Time-control
      experiments were performed in the same subjects. Insulin-mediated glucose uptake
      (M value, mg/kg/min) did not differ between patients with SCD and control
      subjects during the second (6.3 +/- 4.6 and 7.6 +/- 2.6, P =.5), third (7.5 +/-
      4.6 and 9.3 +/- 3.4, P =.4) and fourth hour (8.6 +/- 4.7 and 11.0 +/- 2.9, P =.2)
      of the clamp. At baseline, LBF was higher in the patients with SCD than in the
      controls (3.28 +/- 1.68 and 1.37 +/- 0.47 mL/min/dL, respectively; P =.005).
      Insulin-induced increases in LBF in patients with SCD and in normal subjects were
      not different (P =.9). Respectively, 56% and 24% of the changes in glucose uptake
      could be explained from changes in LBF in the course of the insulin infusion in
      the patients with SCD and controls. We suppose that the comparable insulin
      sensitivity between both groups is due to a compensatory hemodynamic state in SCD
      characterized by vasodilation and increased flow.

PMID- 11288032
TI  - Increased visceral fat accumulation further aggravates the risks of insulin
      resistance in gout.
AB  - We performed the present study to determine the degree of visceral fat
      accumulation and incidence of visceral fat obesity in 138 gout patients who were
      classified as overexcretion type (n = 53) and underexcretion type (n = 85) by
      their levels of uric acid clearance and urinary uric acid excretion. We also
      investigated the relationship between visceral fat accumulation and insulin
      resistance expressed by the homeostasis model assessment (HOMA) index. Visceral
      fat area (VFA)/surface body area (SBA) was significantly increased in patients
      with gout as compared with control subjects (79.7 +/- 30.8 cm(2)/m(2) v 65.1 +/-
      24.1 cm(2)/m(2), P <.001). It was also shown that VFA/SBA in the gout
      overexcretion group was significantly increased as compared with the gout
      underexcretion group (88.3 +/- 32.8 cm(2)/m(2) v 74.3 +/- 28.3 cm(2)/m(2), P
      <.01). Although the incidence of visceral fat obesity (VFO) was not different
      between gout patients and control subjects, the incidence of VFO was
      significantly higher in the gout overexcretion type than the gout underexcretion
      type (19 of 53 v 11 of 85, P <.01). Further, there was a significant relationship
      between visceral fat area and HOMA index. Gout patients possess some factors that
      are included in the insulin resistance syndrome, irrespective of the presence of
      VFO, and the insulin resistance risk factors observed in gout become more
      prominent when it is complicated with VFO. Our results suggest that gout
      patients, especially the overexcretion type who have greater levels of visceral
      fat accumulation, may be more vulnerable to atherosclerotic diseases.

PMID- 11288033
TI  - Metabolic responses to moderate exercise in lambs with aortopulmonary shunts.
AB  - In a previous study we found, after an overnight fast of 18 hours, a lower
      arterial glucose concentration and a depressed glycogenolysis in lambs with
      aortopulmonary left-to-right shunts. During exercise, glucose and free fatty
      acids (FFA) concentrations normally increase. The aim of this study was to
      investigate whether the shunt lambs could compensate for a depressed
      glycogenolysis by increasing gluconeogenesis and by increasing levels of blood
      substrates such as FFA and glycerol during exercise. Therefore, we investigated
      glucose kinetics, with [U-(13)C]glucose, in five 7-week-old shunt and 7 control
      lambs of a similar age, at rest and during moderate exercise (treadmill; 50% of
      VO(2) peak). The glucose production rate and the rate of disappearance of glucose
      were lower in shunt than in control lambs, both at rest and during exercise. We
      found no difference in metabolic clearance rate of glucose, glucose recycling, or
      gluconeogenesis between both groups of lambs. Glycogenolysis was at rest lower in
      shunt than in control lambs and tended to be lower during exercise. The arterial
      concentrations of pyruvate, lactate, FFA, and total and free glycerol increased
      during exercise in both groups of lambs. In conclusion, shunt lambs have lower
      arterial glucose concentrations than control lambs, both at rest and during
      moderate exercise. This was due to a lower glucose production rate, in particular
      a lower glycogenolysis. In addition, the reduced glycogenolysis rate was not
      offset by an increase in gluconeogenesis nor by an increase in other substrates
      that can be utilized by working muscles.

PMID- 11288034
TI  - Thiazolidinediones and glucocorticoids synergistically induce differentiation of
      human adipose tissue stromal cells: biochemical, cellular, and molecular
      analysis.
AB  - While adipocyte differentiation has been studied extensively in murine cultures,
      the lack of a readily available preadipocyte model has hindered equivalent
      studies in man. We describe methods for the isolation and culture of primary
      human stromal cells from surgical adipose tissue specimens. In vitro, the stromal
      cells rapidly differentiate in response to a combination of adipogenic agents.
      Among these, glucocorticoids and thiazolidinediones act together to induce the
      formation of lipid vacuoles within the cells. These morphologic changes accompany
      the increased expression of 2 characteristic adipocyte proteins, the cytoplasmic
      enzyme glycerol phosphate dehydrogenase (GPDH) and the secreted cytokine leptin.
      Likewise, stromal cell differentiation results in elevated mRNA levels for the
      fatty acid binding protein aP2 and the adipogenic regulatory transcription
      factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome
      proliferator-activated receptor gamma (PPARgamma) in addition to leptin. The in
      vitro differentiated stromal cells exhibit a lipolytic response to beta
      adrenergic agonists, comparable to that reported with primary human adipocytes.
      These studies demonstrate the validity of human adipose tissue-derived stromal
      cells as a reliable in vitro model for investigations of adipocyte metabolism in
      humans.

PMID- 11288035
TI  - Troglitazone prevents the rise in visceral adiposity and improves fatty liver
      associated with sulfonylurea therapy--a randomized controlled trial.
AB  - Monotherapy with sulfonylurea may result in the exhaustion of pancreatic beta
      cell function, fat accumulation, and dyslipidemia. We examined the possibility of
      dose reduction by administering sulfonylurea together with troglitazone, and
      investigated changes in insulin secretion and fat deposition. Seventy-eight
      patients with type 2 diabetes adequately controlled with glibenclamide were
      randomly allocated to a troglitazone (400 mg/d)-added group (n = 40) or a control
      group without placebo (n = 38) and monitored for 24 weeks. The daily dose of
      glibenclamide was adjusted to maintain stable HbA(1c) levels. Fat accumulation to
      the liver and thigh muscle were measured in mean Hounsfield units determined on
      computed tomography (CT) scan. Visceral fat accumulation (V), subcutaneous fat
      accumulation (S), and the V/S ratio were also determined by CT scan. The daily
      dose of glibenclamide and serum fasting insulin level in the troglitazone-added
      group significantly decreased (from 4.05 +/- 2.50 mg/d to 1.84 +/- 1.65 mg/d and
      from 8.47 +/- 4.62 microU/mL to 6.49 +/- 3.28 microU/mL, respectively) during the
      observation period compared with the control group (P < .01 and P < .01,
      respectively). Serum triglyceride and homeostasis model insulin resistance index
      (HOMA-R) in the troglitazone-added group decreased significantly in comparison to
      the control group (P < .05 and P < .01, respectively). The mean Hounsfield units
      of liver significantly decreased in the control group compared with the
      troglitazone-added group (P < .05). Visceral fat area and the V/S ratio
      significantly increased in the control group compared with the troglitazone-added
      group (P < .01 and P < .01, respectively). Glibenclamide monotherapy resulted in
      fat accumulation accompanied by dyslipidemia. An alternate conclusion is that
      troglitazone reversed type 2 diabetes (not sulfonylurea)-associated fat
      accumulation. The addition of troglitazone decreased daily doses of
      glibenclamide, preserved fasting insulin secretion, improved fat accumulation in
      liver, and prevented dyslipidemia.

PMID- 11288036
TI  - Streptozotocin-induced diabetes decreases rat sarcolemmal lactate transport.
AB  - Impaired lactate metabolism is a metabolic disorder, which is not fully
      understood in the diabetic state including streptozotocin (STZ)-induced diabetes.
      We investigated whether STZ-induced diabetes results in altered lactate exchanges
      using the rat muscle sarcolemmal vesicles (SV) model. Fifteen days after diabetes
      onset (1 STZ-injection, 65 mg/kg, intraperitoneal [IP]), rats had higher blood
      and muscle lactate concentrations compared with normal rats (1.50 +/- 0.09 v 1.95
      +/- 0.21 mmol/L (not significant [NS]) and 21.02 +/- 1.26 v 25.53 +/- 0.98
      mmol/kg wet weight (ww); P < .05). The initial rate of lactate uptake was
      measured at various external lactate concentrations using SV of both group in
      zero-trans conditions. STZ-induced diabetes decreased the initial rate of total
      lactate influx at external lactate concentrations from 1 to 100 mmol/L (P < .05).
      This decrease in lactate transport was found in addition to an increased free
      radical production, as indicated by a significant increase in malonedialdehyde
      (MDA) concentration (64.3 +/- 8.7 v 100.3 +/- 13.5 nmol. g(-1) ww, P < .05),
      coupled with a higher glutathione peroxidase (Gpx) activity (48.03 +/- 3.13 v
      84.7 +/- 15.01 micromol. min(-1). mg(-1) protein, P < .05) in red gastrocnemius.
      We concluded that STZ-induced diabetes decreases total lactate transport activity
      in rat SV and is associated with increased muscular oxidative stress.

PMID- 11288037
TI  - Contributions of total body fat, abdominal subcutaneous adipose tissue
      compartments, and visceral adipose tissue to the metabolic complications of
      obesity.
AB  - Obesity is related to the risk for developing non-insulin-dependent diabetes
      mellitus (NIDDM), hypertension, and cardiovascular disease. Visceral adipose
      tissue (VAT) has been proposed to mediate these relationships. Abdominal
      subcutaneous adipose tissue (SAT) is divided into 2 layers by a fascia, the
      fascia superficialis. Little is known about the radiologic anatomy or metabolic
      correlates of these depots. The objective of this study was to relate the amounts
      of VAT, SAT, deep subcutaneous abdominal adipose tissue (DSAT), and superficial
      subcutaneous abdominal adipose tissue (SSAT) to gender and the metabolic
      complications of obesity after adjusting for total body fat and to discuss the
      implications of these findings on the measurement of adipose tissue mass and
      adipose tissue function. The design was a cross-sectional database study set in a
      nutrition research center. Subjects included 199 volunteers participating in
      nutrition research protocols who also had computed tomography (CT) and dual
      energy x-ray absorptiometry (DEXA) measurement of body fat. The amount of DSAT
      was sexually dimorphic, with women having 51% of the subcutaneous abdominal fat
      in the deep layer versus 66% for men (P <.05). Abdominal fat compartments were
      compared with metabolic variables before and after adjusting for body fat
      measured by DEXA using 2 separate methods. The unadjusted correlation
      coefficients between the body fat measures, R(2), were largest for fasting
      insulin and triglyceride and smaller for high-density lipoprotein (HDL)
      cholesterol and blood pressure. A large portion of the variance of fasting
      insulin levels in both men and women was explained by total body fat. In both men
      and women, the addition of VAT and subcutaneous abdominal adipose tissue depots
      only slightly increased the R(2). In men, when body fat compartments were
      considered independently, DSAT explained a greater portion of the variance (R(2)
      =.528) in fasting insulin than VAT (R(2) =.374) or non-VAT, non-DSAT subcutaneous
      adipose tissue (R(2) =.375). These data suggest that total body fat is a major
      contributor to the metabolic sequelae of obesity, with specific fat depots, VAT,
      and DSAT also making significant contributions.

PMID- 11288039
TI  - Gln27Glu variant of the beta2-adrenergic receptor gene is not associated with
      obesity and diabetes in Japanese-Americans.
AB  - The beta(3)-adrenergic receptor (AR) gene variant (Trp64Arg) has been reported to
      be associated with obesity and insulin resistance in humans. However, this
      association remains controversial. We investigated the relationships between the
      beta(2)-AR gene variant (Gln27Glu) and obesity, insulin resistance, and serum
      lipids in Japanese-Americans. The frequency of an abnormal Gln27Glu allele in the
      beta(2)-AR gene in 652 subjects was 0.092 in males, 0.077 in females, and 0.084
      overall, markedly lower than the previously reported value of 0.4 in Caucasian
      men and women. In both males and females, there were no differences in the
      indices of obesity, insulin resistance, and serum lipid levels between the
      subjects with and without the beta(2)-AR gene (Gln27Glu) variant in patients with
      normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes
      (DM). The frequency of the beta(2)-AR gene (Gln27Glu) variant tended to increase
      with worsening of glucose tolerance, but the differences were not statistically
      significant. Furthermore, there were no differences in the frequency of the
      beta(2)-AR gene variant in either males or females with obesity (body mass index
      [BMI], > or = 25.2). Even in Japanese-Americans, who have a more westernized life
      style than Japanese, the association of the beta(2)-AR gene (Gln27Glu) variant
      with the parameters of obesity, insulin resistance, and serum lipid level has yet
      to be clarified. We conclude that the beta(2)-AR gene (Gln27Glu) variant might
      not be an important factor for obesity or IGT in Japanese subjects.

PMID- 11288038
TI  - Effects of dietary restriction on appendicular bone in the SENCAR mouse.
AB  - Peptide hormones, cytokines, and growth factors regulate cellular metabolism by
      stimulating second messenger signal transduction cascades in target tissues. A
      mutation in the regulatory domain of protein kinase C (PKC) in SENCAR (sensitive
      to carcinogenesis) mice renders them extremely sensitive to diacylglycerol and
      phorbol esters, resulting in rapid growth, high free radical generation,
      carcinogenesis, and metabolic bone disease. Dietary restriction (DR) normalizes
      PKC and ameliorates adverse downstream effects, including carcinogenesis, in
      SENCAR mice. We hypothesized that DR sufficient to ameliorate carcinogenesis
      would prevent or delay the early onset of metabolic bone disease in SENCAR mice.
      Male mice were assigned to 1 of 4 feeding groups from 10 to 16 weeks of age (the
      critical period when metabolic bone disease develops): ad libitum (AL)-fed; AL
      antioxidant (0.07% thioproline)-fed; 40% DR; or 40% DR antioxidant-fed. Femoral
      bone mass was determined gravimetrically. Tibial total, cortical, and trabecular
      bone mineral density (BMD) were determined by quantitative computed tomography.
      Body weight, femoral bone mass, and tibial cortical BMD were lower in DR than in
      AL mice. However, tibial total and trabecular BMD were higher in DR than in AL
      mice. Serum calcitonin, the hormone that inhibits the osteoclastic bone
      resorption that is most notable in trabecular bone, was 2-fold higher in DR than
      in AL-fed mice. Dietary thioproline had no major effects. Thus, DR sufficient to
      ameliorate carcinogenesis in SENCAR mice did not prevent early-onset metabolic
      bone disease, but it had a beneficial effect on tibial trabecular BMD that
      occurred at the apparent expense of cortical BMD. DR in SENCAR mice was also
      associated with elevated serum calcitonin, which may inhibit osteoclastic
      resorption and account for trabecular bone conservation in this model. In
      conclusion, PKC or the downstream metabolic processes regulated by it appear to
      play previously unrecognized roles in the regulation of tibial trabecular BMD and
      serum calcitonin in SENCAR mice.

PMID- 11288040
TI  - Chitotriosidase genotype and serum activity in subjects with combined
      hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and
      bezafibrate.
AB  - Chitotriosidase, an enzyme involved in the degradation of chitin-containing
      pathogens with unclear function in humans, has been proposed as a marker of lipid
      accumulation in macrophages in different lipid-storage diseases, including
      atherosclerosis. To evaluate (1) if lipid-lowering treatment could modify serum
      chitotriosidase activity and (2) be useful in monitoring lipid-lowering
      treatment, we have analyzed this enzyme activity in the participants in the
      Atozvastatin Versus Bezafibrate in Mixed Hyperlipidemia (ATOMIX) study, a double
      blind, comparative, and randomized study comparing the efficacy of atorvastatin
      and bezafibrate in mixed hyperlipidemia. Because a common genetic deficiency of
      chitotriosidase modifies serum quitotriosidase activity, this genetic variation
      was also studied. Seven subjects of 116 (6.03%) were homozygous, and 46 (39.6%)
      were heterozygous for the defective allele. Mean serum quitotriosidase activity
      correlated with allele dosage, as it was found to be of 0, 59.8 +/- 52.6 and 81.2
      +/- 41.6 nmol/mL/h, in homozygotes for the defective allele, heterozygotes, and
      homozygotes for the wild-type allele, respectively (P =.0011 for the difference
      between the last 2 groups). However, this enzyme activity was not found to
      correlate with lipid levels before and after treatment with either atorvastatin
      or bezafibrate, and neither with the intensity of the lipid lowering. These
      results do not support the use of serum chitotriosidase activity as a biologic
      marker of atherosclerotic plaque modification related to hypolipidemic treatment.

PMID- 11288041
TI  - Alcohol and glucose counterregulation during acute insulin-induced hypoglycemia
      in type 2 diabetic subjects.
AB  - To investigate the influence of alcohol on glucose counterregulation and recovery
      during acute insulin-induced hypoglycemia in type 2 diabetic subjects, 8 diet
      treated type 2 diabetic subjects were examined twice after an overnight fast. A
      graded hyperinsulinemic (1 mU/kg/min, 60 to 195 minutes) euglycemic/hypoglycemic
      clamp was performed with concomitant infusion of 3-(3)H-glucose to assess glucose
      turnover. After a euglycemic baseline period (150 to 180 minutes), 200 mL of
      water was taken either alone or with alcohol (0.4 g/kg body weight). Hypoglycemia
      (plasma glucose nadir, 2.8 mmol/L) was subsequently induced, and the recovery
      period followed after discontinuation of insulin and the variable glucose
      infusion. On both study days, circulating concentrations of insulin and glucose
      were comparable. Alcohol intake markedly increased plasma lactate (area under the
      curve [AUC], recovery period) (244 +/- 30 v 12 +/- 4 mmol/L x 240 minutes; P =
      .00009) and suppressed plasma nonesterified fatty acids (NEFA) (AUC, recovery
      period) (95 +/- 13 v 161 +/- 18 mmol/L x 240 minutes; P = .0008). No differences
      were found in the counterregulatory response of catecholamines, cortisol, and
      growth hormone (GH). However, alcohol intake decreased peak glucagon
      significantly (155 +/- 12 v 200 +/- 17 pg/mL; P = .038). In diet-treated, mild
      type 2 diabetic subjects, alcohol does not modify recovery from insulin-induced
      hypoglycemia.

PMID- 11288042
TI  - Congenic BB.SHR rat provides evidence for effects of a chromosome 4 segment
      (D4Mit6-Npy approximately 1 cm) on total serum and lipoprotein lipid
      concentration and composition after feeding a high-fat, high-cholesterol diet.
AB  - Congenic BB.SHR (previously referred to as BB.LL) rats were generated by
      transferring the segment of chromosome 4 flanked by the D4Mit6 and Spr loci from
      the spontaneously hypertensive rat (SHR/Mol) onto the genetic background of the
      diabetes-prone BB/OK rat. In this study, the influence of the above-mentioned
      region of chromosome 4 on triglyceride, cholesterol, and phospholipid phenotypes
      after a high-fat, high-cholesterol diet was examined by comparison of BB.SHR
      congenic rats with BB/OK rats. BB/OK and BB.SHR had comparable concentrations of
      basal and postdietary serum insulin, as well as of basal total serum
      triglycerides and had an identical body weight and food intake at the beginning
      of the test period. However, after 4 weeks on the test diet, BB.SHR rats were
      significantly heavier than BB/OK rats and had significantly higher food intake
      and lower total serum triglyceride concentrations. The basal serum leptin level
      was significantly lower, but postdietary serum leptin concentration did not show
      a significant difference between the 2 strains. Furthermore, significantly higher
      basal total serum cholesterol and phospholipid levels were observed in BB.SHR
      rats, but this difference disappeared after feeding the high-fat, high
      cholesterol diet. Postdietary high-density lipoprotein (HDL)(2) cholesterol and
      phospholipid levels were significantly elevated in BB.SHR rats when compared with
      BB/OK rats. The 2 strains also differed slightly, but significantly, with respect
      to the other HDL phospholipid concentrations. In addition to previously described
      differences between BB/OK and BB.SHR rats, the results of this study clearly show
      the impact of genes, lying within the transferred segment, on serum lipid
      phenotypes after high-fat, high-cholesterol diet.

PMID- 11288043
TI  - Serum interleukin-6 and thyroid hormones in rheumatoid arthritis.
AB  - Using rheumatoid arthritis (RA) as a model, we have investigated whether the
      activation of the cytokine system, in particular, activation of interleukin (IL)
      6 production, is a major cause of the depressed serum T(3) seen frequently in the
      nonthyroidal illness syndrome (NTIS). RA was chosen because it is a chronic
      autoimmune disease leading to increased serum IL-6 concentrations. We studied 16
      untreated RA and 35 treated RA patients. Twenty-seven treated and 27 untreated
      patients with noninflammatory musculoskeletal symptoms served as controls. The
      patient groups displayed similar age distribution and nutritional status.
      Untreated RA patients displayed elevations of serum IL-6 (mean, 37.5 pg/mL) and C
      reactive protein (CRP; mean, 41.3 mg/L), consistent with the inflammatory nature
      of their disease. Treated RA patients had significantly reduced serum IL-6 (mean,
      9.9 pg/mL) and CRP (mean, 13.3 mg/L) compared with untreated RA patients, while
      untreated and treated patients with noninflammatory musculoskeletal symptoms had
      near normal serum IL-6 (mean, 2.5, 6.6 pg/mL, respectively) and CRP levels (mean,
      5.8, 8.1 mg/L, respectively). However, there were no significant differences in
      serum concentrations of free T(3) (FT(3)) and free T(4) (FT(4)) between groups,
      and thyroid indices were in the normal range in RA patients. Moreover, no
      significant correlations between serum concentration of IL-6 and any of the
      thyroid hormones were demonstrated for any of the patient groups. In conclusion,
      we have been unable to confirm in RA that IL-6 activation leads to the low T(3)
      state of NTIS.

PMID- 11288044
TI  - The effects of angiotensin-II on lipolysis in humans.
AB  - Adipocytes express many of the proteins of the renin-angiotensin system including
      angiotensinogen and AT(1)-receptors. A principal function of adipocyte tissue is
      the provision of energy substrate through lipolysis. This study was undertaken to
      determine if angiotensin-II (Ang-II) infusion or blockade of the renin
      angiotensin system by angiotensin-converting enzyme (ACE) inhibitor therapy with
      enalapril altered lipolytic activity and substrate oxidation. Eleven healthy male
      subjects were enrolled in the first study and postabsorptive whole-body lipolysis
      activity was measured using a stable isotope of glycerol ((2)H(5)-glycerol).
      Substrate oxidation was determined using indirect calorimetry in the Clinical
      Research Center. Subjects were then sequentially treated with low-dose Ang-II
      infusion (0.3 and then 1.0 ng/kg/min) on separate days, and the lipolysis and
      oxidation studies were repeated. Lastly, each subject was treated with 2 weeks of
      ACE inhibitor with enalapril (20 mg daily) and underwent lipolysis and oxidation
      studies for a fourth time. In a second study, 14 healthy male subjects were
      enrolled and underwent an identical baseline lipolysis and substrate oxidation
      assessment. These subjects then received an Ang-II infusion at pressor doses (10
      ng/kg/min), and changes in lipolytic activity and substrate oxidation were
      measured again. In the first study, there was no effect on lipolysis activity
      from low-dose Ang-II infusion (baseline lipolysis activity (mean +/- SD) 2.06 +/-
      0.55 micromol/kg/min, 2.10 +/- 0.69 micromol/kg/min after 0.3 ng/kg/min, and 2.32
      +/- 0.56 micromol/kg/min after 1.0 ng/kg/min) or enalapril therapy (2.35 +/- 1.00
      micromol/kg/min). In the second study, the larger dose of Ang-II increased blood
      pressure by 14/17 mm Hg, but there was no effect on lipolysis activity (1.36 +/-
      0.49 micromol/kg/min v 1.63 +/- 0.82 micromol/kg/min). Substrate oxidation rates
      were largely unaffected by Ang-II infusions or enalapril therapy. There was no
      evidence that treatment with subpressor or pressor dosages of Ang-II produced a
      significant alteration in lipolytic activity. Moreover, blockade of the renin
      angiotensin system with enalapril was equally unremarkable in its effects on
      whole-body lipolysis. These data support the general concept that the renin
      angiotensin system in adipocytes serves more to regulate the regional blood flow
      to adipose tissue and the size and number of fat cells rather than participating
      directly in the regulation of energy substrate.

PMID- 11288045
TI  - Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with
      increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid
      absorption in Korean men.
AB  - The alanine to threonine substitution at codon 54 (Ala54Thr) of the fatty acid
      binding protein 2 (FABP2) gene has been reported to be associated with increased
      fat oxidation and insulin resistance in several populations. It has been
      hypothesized that Ala54Thr substitution results in enhanced intestinal uptake of
      fatty acids and thereby an impairment of insulin action, but this hypothesis has
      not been proven in vivo. We studied the association between the Ala54Thr
      polymorphism of the FABP2 gene and intestinal (3)H-oleic acid absorption, as well
      as basal insulin level, basal metabolic rate, and fat oxidation rate in 96
      healthy young Korean men. Among our subjects, the allele frequency of the
      Ala54Thr substitution was 0.34. Subjects with Thr54-encoding allele were found to
      have a higher mean fasting plasma insulin concentration and a higher basal fat
      oxidation rate compared with the subjects who were homozygous for the Ala54
      encoding allele. However, there was no significant difference in basal metabolic
      rate or (3)H-oleic acid absorption according to the FABP2 gene polymorphism.
      These results suggest that the Ala54Thr substitution in the FABP2 gene is
      associated with increased fat oxidation and hyperinsulinemia in normal Korean
      men, but these effects are not mediated by an increase in the intestinal fatty
      acid absorption.

PMID- 11288046
TI  - Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese
      Japanese type 2 diabetic patients.
AB  - The aim of the present study was to investigate the effect of bezafibrate on
      insulin sensitivity and insulin secretion in 30 non-obese Japanese type 2
      diabetic patients with hypertriglyceridemia (serum triglycerides > 150 mg/dL).
      Insulin sensitivity was measured with homeostasis model assessment insulin
      resistance (HOMA-IR) proposed by Matthews et al. HOMA-B-cell function, proposed
      by Matthews et al validated against minimal model-derived insulin secretion, was
      used to assess pancreatic insulin function. Twenty-two patients were treated with
      glibenclimide and the rest were treated with diet alone. All patients were
      treated with bezafibrate (400 mg/d) for 3 months. There were no changes in diet
      and the dose of any medications used throughout the study. Fasting glucose,
      insulin, triglycerides, HDL cholesterol, and total cholesterol levels were
      measured before and after treatment of bezafibrate. After treatment of
      bezafibrate for 3 months, serum triglyceride levels significantly decreased from
      277 +/- 30 to 139 +/- 9 mg/dL (P <.001) and serum HDL cholesterol levels
      increased significantly from 45 +/- 2 to 52 +/- 2 mg/dL (P =.003). Serum
      cholesterol level was unchanged during the study (198 +/- 7 v 201 +/- 7 mg/dL, P
      =.383). Fasting glucose (163 +/- 8 v 139 +/- 6 mg/dL, P =.006) significantly
      decreased after the treatment with bezafibrate. HbA1c levels decreased, although
      not statistically significant (7.50 +/- 0.25 v 7.17% +/- 0.19%, P =.147). On the
      other hand, fasting insulin (9.3 +/- 0.7 v 7.3 +/- 0.5 microU/mL, P =.010) and
      HOMA-IR (3.61 +/- 0.24 to 2.53 +/- 0.20, P <.001) levels decreased significantly
      after the treatment with bezafibrate. In contrast, HOMA-B-cell function did not
      change during the study (41.4 +/- 5.5 v 41.8 +/- 4.7, P =.478). There was no
      significant difference in body mass index (BMI) levels before and after the
      therapy (23.0 +/- 0.4 v 23.1 +/- 0.4 kg/m(2), P =.483). From these results, it
      can be concluded that bezafibrate reduces serum triglycerides, insulin
      resistance, and fasting blood glucose levels in non-obese Japanese type 2
      diabetic patients.

PMID- 11288047
TI  - Carbohydrate metabolism during exercise in females: effect of reduced fat
      availability.
AB  - This study examined the effect of reduced plasma free fatty acid (FFA)
      availability on carbohydrate metabolism during exercise. Six untrained women
      cycled for 60 minutes at approximately 58% of maximum oxygen uptake after
      ingestion of a placebo (CON) or nicotinic acid (NA), 30 minutes before exercise
      (7.4 +/- 0.5 mg.kg(-1) body weight), and at 0 minutes (3.7 +/- 0.3 mg.kg(-1)) and
      30 minutes (3.7 +/- 0.3 mg.kg(-1)) of exercise. Glucose kinetics were measured
      using a primed, continuous infusion of [6,6-(2)H] glucose. Plasma FFA (CON, 0.86
      +/- 0.12; NA, 0.21 +/- 0.11 mmol.L(-1) at 60 minutes, P <.05) and glycerol (CON,
      0.34 +/- 0.05; NA, 0.10 +/- 0.04 mmol.L(-1) at 60 minutes, P <.05) were
      suppressed throughout exercise. Mean respiratory exchange ratio (RER) during
      exercise was higher (P <.05) in NA (0.89 +/- 0.02) than CON (0.83 +/- 0.02).
      Plasma glucose and glucose production were similar between trials. Total glucose
      uptake during exercise was greater (P <.05) in NA (1,876 +/- 161 micromol.kg(-1))
      than in CON (1,525 +/- 107 micromol.kg(-1)). Total fat oxidation was reduced (P
      <.05) by approximately 32% during exercise in NA. Total carbohydrate oxidized was
      approximately 42% greater (P <.05) in NA (412 +/- 40 mmol) than CON (290 +/- 37
      mmol), of which, approximately 16% (20 +/- 10 mmol) could be attributed to
      glucose. Plasma insulin and glucagon were similar between trials. Catecholamines
      were higher (P <.05) during exercise in NA. In summary, during prolonged moderate
      exercise in untrained women, reduced FFA availability results in a compensatory
      increase in carbohydrate oxidation, which appears to be due predominantly to an
      increase in glycogen utilization, although there was a small, but significant,
      increase in whole body glucose uptake.

PMID- 11288048
TI  - Effect of estrogen on serum DHEA in younger and older women and the relationship
      of DHEA to adiposity and gender.
AB  - This case-controlled study consisted of 2 parts. The objective of part 1 was to
      determine the relationship between DHEA, body mass index (BMI), and age in young
      males, young females, and postmenopausal (PM) females. Part 2 examined the
      effects of estrogen on DHEA by analyzing the relationship between DHEA and age in
      young females on and off oral contraceptives (OCs) and PM females on and off
      estrogen or hormone replacement therapy (ERT/HRT). The study was performed at the
      Obstetrics and Gynecology Clinic, Texas Tech Health Sciences Center-Amarillo,
      Exercise Physiology Laboratory at Southeastern Louisiana University, and Woman's
      Health Research Institute, Woman's Hospital, Baton Rouge, LA. Part 1 groups
      consisted of: (1) young males between the ages of 18 to 40 years; (2) normally
      cycling females off OCs, ages 18 to 40 years; and (3) PM females older than 40
      years not receiving ERT/HRT. Part 2 groups consisted of: (1) normally cycling
      females on OCs, ages 18 to 40 years;, (2) normally cycling females off OCs, ages
      18 to 40 years; (3) PM females 50 years or older not receiving ERT/HRT; and (4)
      PM females 50 years or older receiving ERT/HRT. The main outcome measure was
      serum DHEA concentrations. For part 1, there were significant (P <.05) inverse
      relationships between DHEA and age for young males; young females, off OCs; PM
      females, no ERT/HRT r = -.44, -.26, and -.25, respectively. There were no
      significant relationships between DHEA and BMI for any of the groups. DHEA
      concentrations were significantly higher in young males than young females even
      after accounting for age. For part 2, DHEA concentrations were significantly
      higher in young females off OCs compared with young females on OCs, and
      significantly higher in PM women off ERT/HRT than those on ERT?HRT. There were
      significant inverse relationships between DHEA and age for young females and PM
      females on and off ERT/HRT. From these findings, we conclude that there is an
      inverse relationship between DHEA and age for young males, young females off OCs,
      and PM females, no ERT/HRT. No relationship between BMI and DHEA was observed in
      these same 3 groups. These results agree with previous findings in young men, but
      differ from previous findings in obese young females. The data also suggest that
      estrogen treatment (OCs and ERT/HRT) suppresses DHEA concentrations in
      premenopausal and PM females, and that DHEA declines with age in PM females
      regardless of estrogen treatment.

PMID- 11288049
TI  - Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and
      colonic function.
AB  - We tested the effects of feeding a diet very high in fiber from fruit and
      vegetables. The levels fed were those, which had originally inspired the dietary
      fiber hypothesis related to colon cancer and heart disease prevention and also
      may have been eaten early in human evolution. Ten healthy volunteers each took 3
      metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and
      nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and
      legumes (early agricultural diet); or low-fat (contemporary therapeutic diet).
      All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d).
      Compared with the starch-based and low-fat diets, the high-fiber vegetable diet
      resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol
      (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d,
      P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid
      outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal
      bulk, the actual concentrations of fecal bile acids were lowest on the vegetable
      diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1
      week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable
      diet reflecting large fecal steroid losses. We conclude that very high-vegetable
      fiber intakes reduce risk factors for cardiovascular disease and possibly colon
      cancer. Vegetable and fruit fibers therefore warrant further detailed
      investigation.

PMID- 11288056
TI  - Dimethylsulfoxide-stabilized conformer of guanine-adenine repeat strand of DNA.
AB  - Circular dichroism spectroscopy and other methods are used to show that the
      addition of dimethylsulfoxide causes reversible folding of the (GA)(10) strand of
      DNA into an ordered single-stranded conformer. The ordered conformer melts in a
      cooperative way and it does not contain protonated adenine. The (TA)(10),
      (A)(20), and (G)(20) are all unstable in this conformer. To the best of our
      knowledge, this is the first known ordered conformer of DNA that is stabilized by
      dimethylsulfoxide. This conformer might be a DNA analog of the protein alpha
      helix, which is an interesting idea for thinking about the evolution of DNA.

PMID- 11288057
TI  - Surface-enhanced Raman and steady fluorescence study of interaction between
      antitumoral drug 9-aminoacridine and trypsin-like protease related to metastasis
      processes, guanidinobenzoatase.
AB  - Fluorescence spectroscopy and surface-enhanced Raman spectroscopy (SERS) were
      applied to study the interaction of the antitumoral drug 9-aminoacridine (9AA)
      with a trypsin-like protease guanidinobenzoatase (GB) extracted from a mouse
      Erlich tumor. As a consequence of this interaction, a strong 9AA exciplex
      emission was detected in the emission fluorescence spectra at certain drug and
      enzyme concentrations. A SERS study was accomplished on silver colloids at
      several excitation wavelengths in order to obtain more information about the
      interaction mechanism. The results derived from Raman spectroscopy indicated that
      9AA in the amino monomeric form may interact with the enzyme by means of two
      different bonds: an ionic bond with a negatively charged amino acid and a ring
      stacking interaction with an aromatic residue placed in the catalytic site of GB.
      This interaction mechanism was responsible for a strong exciplex emission
      detected at a longer wavelength than the expected value of the normal
      fluorescence emission. Moreover, the GB concentration dependence of the
      interaction suggested that the drug was sensitive to the quaternary structure of
      the enzyme.

PMID- 11288058
TI  - New Fourier transform infrared based computational method for peptide secondary
      structure determination. I. Description of method.
AB  - Fourier transform infrared (FTIR) experiments in dimethylsulfoxide, a solvent
      incapable of H donation, demonstrate that H --> D isotopic replacement on the
      amide side of peptide bonds involves modifications of both the position and
      intensity of the amide I band. The effect of the isotopic substitution is
      particularly significant in the 1710-1670 and 1670-1650 cm(-1) regions, which are
      generally associated with beta-turns and alpha-helices. This behavior, attributed
      to the existence of intramolecular H-bonds in the polypeptide chain, is directly
      correlated to the presence of different secondary structures. Utilizing the
      effects induced by isotopic substitution, a method for the quantitative
      determination of the percentage of intramolecular H-bonds and the correlated
      secondary structures is proposed. The method consists of three principal steps:
      resolution of the fine structure of the amide I band with the determination of
      the number and position of the different components; reconstruction of the
      experimentally measured amide I band as a combination of Gaussian and Lorentzian
      functions, centered on the wave numbers set by band-narrowing methods, through a
      curve-fitting program; and quantitative determination of the population of the H
      bonded carbonyls and the correlated secondary structures by comparison of the
      integrated intensities pertaining to the components with homologous wave numbers
      before and after isotopic exchange. The method is tested on a synthetic fragment
      of proocytocin that was previously analyzed by NMR techniques using the same
      solvent systems.

PMID- 11288059
TI  - New Fourier transform infrared based computational method for peptide secondary
      structure determination. II. Application to study of peptide fragments
      reproducing processing site of ocytocin-neurophysin precursor.
AB  - A new method for the quantitative determination of the percentage of
      intramolecular H-bonds, based on Fourier transform infrared techniques, is
      applied to the conformational analysis of a series of synthetic peptides spanning
      the processing site of the ocytocin and neurophysin precursor. Even though the
      method uses traditional tools such as Fourier self-deconvolution, the Nth
      derivative, and curve-fitting procedures for the analysis of the spectra, the
      assignment of the absorptions due to peptide groups participating into secondary
      structures is based on the direct observation and quantification of the isotopic
      effect induced on the groups participating in intramolecular H-bonds in the
      presence of organic solvents. This permits the quantification of the different
      populations of molecules containing intramolecular H-bonds involved in beta-turns
      and alpha-helices. The results are consistent with those previously obtained by
      NMR techniques in the same solvent systems.

PMID- 11288060
TI  - Optical properties of ovalbumin in 0.130-2.50 microm spectral region.
AB  - In our continuing series of measurements of the complex index of refraction for
      representative samples of biological materials, we measured ovalbumin (egg
      albumin) over the spectral region from 0.130 (76,923 cm(-1)) to 2.50 microm (4000
      cm(-1)). Films of ovalbumin suitable for optical analyses were prepared and
      measured in addition to solutions of ovalbumin in water. We show several examples
      of how the methods used in this study produced accurate results for this complex
      and difficult to measure material. The present work is applicable to quantitative
      optical studies involving ovalbumin and other serpin proteins, as well as the
      study of proteinaceous toxins.

PMID- 11288061
TI  - Solid-phase synthesis of 2,4-diaminoquinazolines.
AB  - A highly efficient and versatile solid-phase synthesis of 2,4-diaminoquinazoline
      library from 2,4-dichloroquinazolines and amines using 3,5-dimethoxy 4
      formylphenoxy-polystyrene resin is described.

PMID- 11288062
TI  - Novel alpha-hydroxyethyl-polystyrene, alpha-chloroethyl-polystyrene and alpha
      amino-oxyethyl-polystyrene linkers on the Multipin solid support for solid-phase
      organic synthesis.
AB  - A simple method for the generation of three novel linkers, alpha-hydroxyethyl
      polystyrene, alpha-chloroethyl-polystyrene and alpha-amino-oxyethyl-polystyrene
      on Multipin supports (SynPhase Crowns) has been developed. Applications of these
      linkers have been successfully demonstrated for solid-phase synthesis of
      dipeptide, oxime, and hydroxamic acid compounds in good yields and purities.

PMID- 11288063
TI  - Symmetric building blocks and combinatorial functional group transformation as
      versatile strategies in combinatorial chemistry.
AB  - A combination of symmetric building blocks and combinatorial functional group
      transformation for synthesis of pyrimidines was investigated. The purpose of the
      study was to maximize the return on invested synthetic efforts of reaction
      development for libraries. A representative set of symmetric diacids was coupled
      onto deprotected TentaGel Rink Amide resin. The amino function served as a model
      of a chemical process providing a functional group for additional synthetic
      steps, while the symmetric building blocks served as a model to connect synthesis
      protocols and to switch to a different synthesis paradigm consecutively. The
      reaction sequence was continued in a noncombinatorial step by coupling a
      bifunctional reagent (3-aminoacetophenone) to the remaining carboxy function of
      the symmetric diacid. The ketone served as a model of a reagent prepared for
      combinatorial functional group transformation. The arylmethylketone was reacted
      with a set of aryl- and heteroarylaldehydes to give alpha,beta-unsaturated
      ketones. Subsequently, guanidine, alkyl-, and arylcarboxamidines were introduced
      in combinatorial synthesis of substituted pyrimidines by reaction with the alpha,
      beta-unsaturated ketone functionality. The combination of symmetric building
      blocks and combinatorial functional group transformation created a versatile
      reaction sequence ideally suited for production of libraries from libraries with
      added diversity.

PMID- 11288064
TI  - A selenide linker for "traceless" solid-phase organic synthesis.
AB  - 4-Bromophenethyl alcohol was protected as the THP ether, followed by reaction
      with magnesium and selenium to give the corresponding diselenide. Ether
      deprotection provides a diselenide diol, which is attached to solid-phase resins.
      The polymer-bound selenide anion is then generated, and functions as a traceless
      linker for electrophiles such as alkyl halides.

PMID- 11288066
TI  - Solid-phase reaction monitoring--chemical derivatization and off-bead analysis.
AB  - The aim of this review is to give a compendium of colorimetric assays and
      spectrophotometric-based quantification methods applicable to solid-phase organic
      chemistry. Comprehensive experimental details for commonly employed color tests
      performed on solid support will be documented.

PMID- 11288067
TI  - Infrared spectroscopy in solid-phase synthesis.
AB  - There are many new analytical techniques for the characterization of resin-bound
      substrates and solid-phase reaction monitoring. The aim of this review is to
      focus on applications of the different IR techniques used in solid-phase
      synthesis highlighting some of the recent advances in the field that allow us to
      obtain more than just the usual qualitative information. Many examples will be
      discussed where these new IR techniques have been used for mechanistic and
      kinetic studies of solid-phase reactions.

PMID- 11288068
TI  - High resolution MAS-NMR in combinatorial chemistry.
AB  - High-resolution magic angle spinning (hr-MAS) NMR is a powerful tool for
      characterizing organic reactions on solid support. Because magic angle spinning
      reduces the line-broadening due to dipolar coupling and variations in bulk
      magnetic susceptibility, line widths approaching those obtained in solution-phase
      NMR can be obtained. The magic angle spinning method is amenable for use in
      conjunction with a variety of NMR-pulse sequences, making it possible to perform
      full-structure determinations and conformational analysis on compounds attached
      to a polymer support. Diffusion-weighted MAS-NMR methods such as SPEEDY (Spin
      Echo-Enhanced Diffusion-Filtered Spectroscopy) can be used to remove unwanted
      signals from the solvent, residual reactants, and the polymer support from the
      MAS-NMR spectrum, leaving only those signals arising from the resin-bound
      product. This review will present the applications of high-resolution magic angle
      spinning NMR for use in combinatorial chemistry research.

PMID- 11288069
TI  - FTICR-mass spectrometry for high-resolution analysis in combinatorial chemistry.
AB  - The diversity of compound collections required for finding lead structures in
      pharmaceutical research can be provided by means of combinatorial organic
      chemistry. The resultant enormous number of single compounds but also of compound
      mixtures represents a challenge for the analyst. With the introduction of Fourier
      transform ion cyclotron resonance mass spectrometry (FTICR-MS or FT-MS), a new
      and, as yet, not widespread mass spectrometric technique (a means of analysis of
      such compound libraries with a very high mass resolution) high mass accuracy and
      high sensitivity has become available. Moreover, in combination with electrospray
      ionization (ESI), not only high-throughput measurements via flow-injection
      analysis (FIA) but also coupling with separation techniques such as high
      performance liquid chromatography (HPLC) or capillary electrophoresis (CE) is
      possible. Structural verification by way of decomposing ions (MS(n); n > or = 2)
      using a variety of different dissociation techniques can be performed by FTICR
      MS. This is the first review specifically covering applications of FTICR-MS in
      the field of combinatorial chemistry.

PMID- 11288070
TI  - High-throughput determination of identity, purity, and quantity of combinatorial
      library members using LC/MS/UV/ELSD.
AB  - We have used a high-throughput LC/MS/UV/ELSD method to rapidly determine the
      absolute quantity and purity of 42 organic compounds from seven lead discovery
      libraries. A general calibration curve generated from a different set of 42
      compounds with seven different scaffolds was used in this analysis. We have also
      studied 33 organic compounds with different molecular weight (MW) by
      LC/MS/UV/ELSD to investigate the effect of MW on ELSD response and the accuracy
      for purity and quantity measurement using UV(214) and ELSD. A general ELSD
      calibration curve from these compounds was also generated to quantify 42 library
      compounds. Purity measurement by ELSD underestimates the amounts of impurities
      due to a reduced ELSD response from smaller molecular weight impurities often
      produced in library synthesis. Absolute quantity determination by ELSD is more
      accurate (RSD 28%) than that by UV(214) (48%) using a calibration curve generated
      from the same set of compounds with diverse MWs. Error assessment for the
      measurement of absolute quantity of a class of commercial compounds and a class
      of representing reference compounds from seven diverse lead discovery libraries
      shows that structurally related compounds should be used to generate calibration
      curves to sustain smaller deviation.

PMID- 11288071
TI  - Perspective on hemocompatibility testing.

PMID- 11288072
TI  - Does surface chemistry affect thrombogenicity of surface modified polymers?
AB  - With some exceptions, surface chemistry had little effect on platelet and
      leukocyte activation, and cell deposition, by scanning electron microscopy after
      blood exposure and clotting times among a group of 12 unmodified and plasma
      modified tubings. All materials activated platelets and leukocytes to detectable
      levels, although some materials increased the value of one activation parameter
      but not another. Unmodified materials [polyethylene (PE), Pellethane (PEU),
      latex, nylon, and Silastic] and modified materials (H(2)O plasma treated PE and
      PEU, CF(4) plasma treated PE, fluorinated PEU, NH(4) plasma treated PEU,
      polyethylene imine treated PEU, and heparin treated PEU) were characterised by
      XPS and contact angle. The objective of this project was to define a series of
      assays for the evaluation of hemocompatibility of cardiovascular devices with a
      view to clarify the specific requirements of ISO-10993-4, and to define an
      appropriate screening program for new blood contacting biomaterials. PE, PE-
      CF(4), PE--H(2)0, PEU--F, latex, and PEU-heparin were the exceptions to the
      general observations, although each behaved differently. PE proved to be least
      reactive, whereas PE-CF(4) was most reactive by several assays. Platelet
      microparticle formation (determined by flow cytometry), PTT, postblood exposure
      SEM, total SC5b-9, C3a, and platelet and leukocyte loss (cell counts) were able
      to distinguish differences among these materials, and often, but not always,
      showed expected correlations.

PMID- 11288073
TI  - Novel sol-gel bioactive fibers.
AB  - Bioactive fibers were produced using a sol-gel method. The rheological properties
      of two different sol compositions prepared from a mixture of TEOS, phosphorous
      alkoxide and calcium nitrate, or calcium chloride in a water-ethanol solution,
      are reported. The sols were extruded through a spinneret to produce continuous 10
      microm-diameter fibers. Discontinuous fibers and fibrous mats were prepared by
      air-spraying the multicomponent sols. The sol-gel fibers were converted to the
      bioactive fibers by three different thermal treatments at either 600 degrees, 700
      degrees, or 900 degrees C for 3 h. SEM, BET, EDX, and FTIR were used to
      characterize the morphology and structure of the fibers. The BET measured surface
      area of the fibers sintered at 900 degrees C was 0 m(2)/gm compared to a value of
      200 m(2)/gm for a typical sol-gel-derived particle of similar composition. Both
      the continuous and discontinuous fibers exhibited in vitro bioactivity in a
      simulated body fluid.

PMID- 11288074
TI  - A sol-gel derived bioactive fibrous mesh.
AB  - Nonwoven sheets of bioactive fibers were produced using a sol-gel process. A high
      velocity spray process was used to prepare fibers of two compositions in the
      SiO(2)-CaO-P(2)O(5) ternary system. Both discontinuous fibers and dispersed
      fibers were evaluated. Viscosity and pH of the sol were the two primary
      processing variables studied. The formation of hydroxy carbonate apatite (HCA) on
      the surface of the fibers was used to evaluate the kinetics of the bioactivity in
      a simulated body fluid (SBF). Diffuse reflection infrared fourier transform
      spectroscopic (DRIFTS) analysis confirmed the presence of HCA (P-O). A homogenous
      layer of HCA, as observed with SEM (scanning electron microscopy), typically
      formed after 3-h immersion in the SBF. The concentration of HCA formed was
      greater for samples richer in silica. The new bioactive fiber sheets produced by
      this process are chemically more stable than powders or monoliths prepared from
      similar precursors. Potential applications are as scaffold for both mineralized
      and nonmineralized structural tissues.

PMID- 11288075
TI  - Biodegradable polymer/hydroxyapatite composites: surface analysis and initial
      attachment of human osteoblasts.
AB  - Biodegradable polymer/hydroxyapatite (HA) composites have potential application
      as bone graft substitutes. Thin films of polymer/HA composites were produced, and
      the initial attachment of primary human osteoblasts (HOBs) was assessed to
      investigate the biocompatibility of the materials. Poly(epsilon-caprolactone)
      (PCL) and poly(L-lactic acid) (PLA) were used as matrix materials for two types
      of HA particles, 50-microm sintered and submicron nonsintered. Using ESEM, cell
      morphology on the surfaces of samples was investigated after 90 min, 4 h, and 24
      h of cell culture. Cell activity and viability were assessed after 24 h of cell
      culture using Alamar blue and DNA assays. Surface morphology of the polymer/HA
      composites and HA exposure were investigated using ESEM and EDXA, respectively.
      ESEM enabled investigation of both cell and material surface morphology in the
      hydrated condition. Combined with EDXA it permitted chemical and visual
      examination of the composite. Differences in HA exposure were observed on the
      different composite surfaces that affected the morphology of attached cells. In
      the first 4 h of cell culture, the cells were spread to a higher degree on
      exposed HA regions of the composites and on PLA than they were on PCL. After 24 h
      the cells were spread equally on all the samples. The cell activity after 24 h
      was significantly higher on the polymer/HA composites than on the polymer films.
      There was no significant difference in the activity of the cells on the various
      composite materials. However, cells on PCL showed higher activity compared to
      those on PLA. A polymer surface exhibiting "point exposure" of HA appeared to
      provide a novel and favorable substrate for primary cell attachment. The cell
      morphology and activity results indicate a favorable cell/material interaction
      and suggest that PLA and PCL and their composites with HA may be candidate
      materials for the reconstruction of bony tissue. Further investigations regarding
      long-term biomaterial/cell interactions and the effects of acidic degradation
      products from the biodegradable polymers are required to confirm their utility.

PMID- 11288076
TI  - Cell adhesion to protein-micropatterned-supported lipid bilayer membranes.
AB  - A new method for constructing controlled interfaces between cells and synthetic
      supported lipid bilayer membranes is reported. Microcontact printing is used to
      define squares and grid lines of fibronectin onto glass, which subsequently
      direct the self-assembly of fluid lipid bilayers onto the complementary, uncoated
      regions of the surface. Features of fibronectin as small as 5 microm effectively
      control the lateral organization of the lipid bilayers. These fibronectin
      barriers also facilitate the adhesion of endothelial cells, which exhibit minimal
      adhesion to fluid supported lipid bilayers alone. Cells selectively adhere to the
      features of fibronectin, spanning over and exposing the cells to the intervening
      regions of supported lipid bilayer. Cell spreading is correlated with both the
      geometry and dimensions of the fibronectin barriers. Importantly, lipids
      underlying adherent cells are laterally mobile, suggesting that, in contrast to
      the regions of fibronectin, cells were not in direct contact with the supported
      membrane. Protein micropatterning thus provides a valuable tool for controlling
      supported membranes and for juxtaposing anchorage-dependent cells with lipid
      bilayers. These systems should be generally useful for studying specific
      interactions between cells and biomolecules incorporated into supported
      membranes, and as an approach for integrating living cells with synthetic,
      laterally complex surfaces.

PMID- 11288077
TI  - Induction of collagen mineralization by a bone sialoprotein--decorin chimeric
      protein.
AB  - The observation that hydroxyapatite (HA) formation from metastable solutions can
      be induced by nucleating proteins such as bone sialoprotein (BSP) suggests a
      possible treatment for bone defects. The introduction of a mixture of nucleating
      protein and type I collagen should result in a defect becoming filled with a
      mineralized collagenous matrix that is biologically and mechanically compatible
      and capable of being remodeled. To create a nucleating protein that would
      interact with collagen fibrils, we combined the putative collagen-binding site of
      mouse decorin with one of two putative HA-nucleating sites of pig BSP. The
      resulting chimeric protein induced the formation of HA crystals in a steady-state
      agarose gel system and bound with high affinity to fibrillar type I collagen. The
      addition of chimeric protein to collagen gels perfused with low concentrations of
      calcium and phosphate resulted in the deposition of large, apparently needle
      shaped HA crystals on the surface of collagen fibrils. These findings suggest
      that the BSP-decorin chimeric protein could be capable of inducing the
      mineralization of collagen in vivo.

PMID- 11288079
TI  - Fabrication and characterization of controlled release poly(D,L-lactide-co
      glycolide) millirods.
AB  - A compression-heat molding procedure was developed to fabricate poly(D,L-lactide
      co-glycolide) (PLGA) controlled release drug delivery devices for the local
      treatment of tumors. The drug delivery devices were designed in the shape of a
      cylindrical millirod (1.6-mm diameter, 10-mm length), which allows them to be
      implanted by a modified 14-gauge tissue biopsy needle into tumor tissues via
      image-guided interventional procedures. In this study, the prototype trypan blue
      containing PLGA millirods were fabricated under a compression pressure of 4.6 x
      10(6) Pa and different fabrication temperatures for 2 h. The scanning electron
      microscopy results showed complete polymer annealing for millirods fabricated at
      80 and 90 degrees C, while the cross sections of the 60 and 70 degrees C
      millirods showed incompletely annealed PLGA microspheres and trypan blue powders.
      The density, flexural modulus, and release properties of the PLGA millirods were
      also characterized and compared. The average values of the density and flexural
      modulus of the millirods increased with an increase in fabrication temperature.
      The flexural modulus values of most PLGA millirods were above 1 x 10(8) Pa, which
      provides sufficient stiffness for implantation within the tumor tissue. In
      addition, a Delta c(p) method was developed to determine the loading density of
      trypan blue in the PLGA millirods by differential scanning calorimetry. Results
      from the Delta c(p) measurement showed that trypan blue was homogeneously
      distributed in the millirod. Release studies in phosphate-buffered saline showed
      that the release rate decreased for the millirods fabricated at higher
      temperatures. The times for the release of 50% trypan blue were 5, 25, 25, and 25
      h for millirods fabricated at 60, 70, 80, and 90 degrees C, respectively.
      Millirods fabricated at 90 degrees C had the most reproducible release profiles.
      The results from this study established compression--heat molding as an effective
      method to fabricate controlled release PLGA millirods with sufficient mechanical
      strength and reproducible release profiles for local cancer therapy.

PMID- 11288078
TI  - Injection molding of chondrocyte/alginate constructs in the shape of facial
      implants.
AB  - Over one million patients per year undergo some type of procedure involving
      cartilage reconstruction. Polymer hydrogels, such as alginate, have been shown to
      be effective carriers for chondrocytes in subcutaneous cartilage formation. The
      goal of our current study was to develop a method to create complex structures
      (nose bridge, chin, etc.) with good dimensional tolerance to form cartilage in
      specific shapes. Molds of facial implants were prepared using Silastic ERTV.
      Suspensions of chondrocytes in 2% alginate were gelled by mixing with CaSO(4)
      (0.2 g/mL) and injected into the molds. Constructs of various cell concentrations
      (10, 25, and 50 million/mL) were implanted in the dorsal aspect of nude mice and
      harvested at times up to 30 weeks. Analysis of implanted constructs indicated
      progressive cartilage formation with time. Proteoglycan and collagen constructs
      increased with time to approximately 60% that of native tissue. Equilibrium
      modulus likewise increased with time to 15% that of normal tissue, whereas
      hydraulic permeability decreased to 20 times that of native tissue. Implants
      seeded with greater concentrations of cells increased proteoglycan content and
      collagen content and equilibrium and decreased permeability. Production of shaped
      cartilage implants by this technique presents several advantages, including good
      dimensional tolerance, high sample-to-sample reproducibility, and high cell
      viability. This system may be useful in the large-scale production of precisely
      shaped cartilage implants.

PMID- 11288080
TI  - Significance of the type and the size of biomaterial particles on phagocytosis
      and tissue distribution.
AB  - Particulates generated by dissolution or wear of injected or implanted
      biomaterials may migrate into various tissues and lead to activation of the
      host's inflammatory and immune responses. The purpose of this study was to
      evaluate the relevance of size and chemical composition of biomaterial particles
      on the pattern of particle distribution in host tissues. Adult female B6C3F1 mice
      were injected intraperitoneally with polymethylmethacrylate (PMMA) particles
      (size 1.4 and 6.4 micro in diameter) and polystyrene (PS) particles (size 1.2,
      5.2, and 12.5 micro in diameter), and euthanized 1, 7, and 28 days later.
      Peritoneal exudate cells (PECs) were collected and the number of cells and
      percentage of actively phagocytic cells was determined. Macroscopic examination
      of the tissues in the peritoneal cavity peritoneum revealed visible accumulations
      of the colored PS particles in the adipose tissues adjacent to the spleen and
      pancreas, and caudal to the stomach. Distribution of the PS particles appeared
      similar regardless of the particle size. The location of PMMA particles, which
      were not colored, could not be distinguished from host tissue and could not be
      observed in this manner. Intensive phagocytosis of the small and medium sized
      particles by peritoneal macrophages was observed on day 1, and was diminishing by
      day 7 after injection. The largest PS particles (12.5 micro) were not engulfed by
      the peritoneal macrophages. Histological examination of the spleen, lymph nodes,
      and the adjacent adipose tissues revealed a marked difference in the deposition
      patterns of the two polymers used. PS particles, regardless of size, were
      accumulated primarily in the white adipose tissues adjacent to the spleen and
      pancreas gland, but very few particles were observed in the splenic tissue. On
      the other hand, mice injected with PMMA particles of either size had enlarged and
      activated spleens with marked deposits of particles in the red pulp. These
      results indicate that these PS and PMMA particles induce different patterns and
      intensities of the host response. The chemical makeup of the particle is more
      important in the distribution pattern than is the size of the particle.

PMID- 11288081
TI  - In vivo testing of a new in situ setting beta-tricalcium phosphate cement for
      osseous reconstruction.
AB  - A new in situ setting tricalcium phosphate cement was implanted in 1.5-mm
      trepanation defects in rat femurs. Empty cavities and autologous bone grafts were
      used as controls. Cement resorption and new bone formation were evaluated in
      undecalcified sections with histologic examination, contact microradiographies,
      radiodensitometry, and scanning electron microscopy after 1 and 3 weeks. The
      mechanical integrity was tested in a three-point bending test. The amount of new
      bone formation over time was determined by intravital fluorescence staining. With
      the in situ setting substance, a good filling of the whole trepanation defect was
      achieved without leakage of the paste-like cement. Slow resorption of the cement
      and new bone formation beginning at the edge of the defect were seen after 1
      week. After 3 weeks, resorption was advanced and there was ingrowth of new bone,
      with close contact between cement particles and bone, as shown in histologic
      sections and with a calcium/phosphorus analysis by quantitative line scans of an
      electron microanalysis (SEM-EPMA). This new self-hardening cement is bioactive,
      resorbable, and osteotransductive. It may be usable for the filling of stable
      defects, such as cysts or benign tumors, or for bone supplementation in revision
      arthroplasty.

PMID- 11288082
TI  - Stability of a biological tissue fixed with a naturally occurring crosslinking
      agent (genipin).
AB  - The study was undertaken to investigate the stability of a biological tissue
      fixed with a naturally occurring crosslinking agent (genipin) at distinct elapsed
      storage durations. The glutaraldehyde-fixed counterpart was used as a control.
      Porcine pericardia procured from a slaughterhouse were used as raw materials.
      After fixation, the fixed tissues were sterilized in a graded series of ethanol
      solutions and thoroughly rinsed in phosphate buffered saline for 1 day, and then
      stored in a jar containing sterilized water. The samples were taken out and
      tested for their stability during the durations of 1day through 6 months after
      storage. The stability of each study group was tested by measuring its tensile
      strength, free-amino-group content, and denaturation temperature. Additionally,
      the cytotoxicity of each test sample and its corresponding storage solution were
      investigated in vitro using 3T3 fibroblasts. The results were examined using a
      microscope and 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. It was found that the stability of the genipin-fixed tissue during storage
      was superior to its glutaraldehyde-fixed counterpart. The differences in
      stability between the genipin- and glutaraldehyde-fixed tissues during storage
      may be caused by their differences in crosslinking structure. There was no
      apparent cytotoxicity for both the genipin-fixed tissue and its corresponding
      storage solution throughout the entire course of the study, whereas significant
      cytotoxicity was observed for both the glutaraldehyde-fixed tissue and its
      storage solution. However, the cytotoxicity of the glutaraldehyde-fixed tissue
      decreased with increasing elapsed storage duration, whereas that of its
      corresponding storage solution increased. This suggested that the toxic residues
      remaining in the glutaraldehyde-fixed tissue leached out slowly into its
      corresponding storage solution during the course of storage.

PMID- 11288083
TI  - Synergistic induction of cyclooxygenase-II by bacterial lipopolysaccharide in
      combination with particles of medical device materials in a murine macrophage
      cell line J774A.1.
AB  - Corrosion and wear of implanted medical devices may produce particulate debris,
      leading to acute and chronic inflammatory responses in the host. In the presence
      of biomaterial wear particles, host monocytes/macrophages are activated to
      synthesize or secrete mediators of inflammation. In order to understand the
      mechanisms underlying the host response to particulates and device-associated
      infections, we have focused on the effects of medical device particles on
      macrophage function, because these cells play a pivotal role in the body's
      response to foreign bodies and their interaction with other cellular components
      of the immune system. In order to evaluate the effects of particles of medical
      device materials on functional activities of macrophages, we developed a
      cyclooxygenase-II (COX-II) assay system using J774A.1 macrophages. Constitutive
      cyclooxygenase (COX-I) is present in cells under physiological conditions,
      whereas inducible COX-II is induced by some cytokines, mitogens, and endotoxin,
      presumably in pathological conditions such as inflammation. We have evaluated the
      inductive effects of implant materials, i.e., particles of polymethylmethacrylate
      (PMMA), hydroxyapatite (HA), titanium oxide, and silica, on the activity of COX
      II using thin layer chromatography of prostaglandin D(2) (PGD(2)) formed from [1
      (14)C]-labeled arachidonic acid (AA). Also, we have assessed the synergistic
      effects of these particles on lipopolysaccharide (LPS)-mediated macrophage
      activation. Addition of LPS to these particles increased PGD(2) production
      several-fold greater than the addition of any inducer alone. Our results
      indicated that device-associated infections could enhance inflammatory responses
      to the wear particles in subjects with medical implants or in whom particulate
      biomaterials are used for clinical purposes. The use of this model COX-II assay
      system may lead to the identification of inflammatory potentials for implant
      materials more specifically than present in vivo assays.

PMID- 11288084
TI  - Surface characterization and platelet adhesion studies of self-assembled
      monolayer with phosphonate ester and phosphonic acid functionalities.
AB  - Because of its well-defined surface configuration and creative chemical
      structure, an alkanethiol self-assembled monolayer (SAM) on gold is a model
      surface for a blood compatibility investigation. In this study two laboratory
      synthesized long-chain alkanethiols, HS(CH(2))(10)PO(3)-(C(2)H(5))(2) and
      HS(CH(2))(10)PO(3)H(2), were employed for the direct preparation of SAMs with
      nonionic and ionic functional groups. Various instrumental analyses confirmed the
      high purity of the phosphonate ester and phosphonic acid terminated alkanethiols.
      The surface characterization results showed the -PO(3)H(2) terminated SAM was
      more hydrophilic than the -PO(3)(C(2)H(5))(2) one. Higher hysteresis values for
      the -PO(3)(C(2)H(5))(2) and -PO(3)H(2) terminated SAMs were noted, which were
      possibly due to the steric hindrance of the bulky terminal groups. In addition,
      the O(2) plasma + EtOH-rinse pretreated Au sample was hydrophilic because of the
      residual gold oxide on the surface. This finding was supported by electron
      spectroscopy for chemical analysis (ESCA) as well. The ESCA analysis also
      indicated bulky and polar terminal groups [-PO(3)(C(2)H(5))(2) and -PO(3)H(2)]
      were situated in the outermost layer of its monolayer. The platelet reactivity on
      the SAM with the nonionic group -PO(3)(C(2)H(5))(2) was less than those of the
      ionic terminated SAMs -COOH and -PO(3)H(2). The O(2) plasma + EtOH-rinse
      pretreated gold substrate exhibited the least platelet-activating surface among
      the different pretreated Au substrates studied.

PMID- 11288085
TI  - Effect on composition of dry mechanical grinding of calcium phosphate mixtures.
AB  - For diverse reasons, calcium phosphates used to prepare hydraulic calcium
      phosphate cements can be ground mixed. The grinding with a rotating micromill of
      monocalcium phosphate monohydrate or anhydrous, dicalcium phosphate dihydrate or
      anhydrous with calcium oxide, calcium hydroxide, calcium carbonate, tetracalcium
      phosphate, or alpha- or beta-tricalcium phosphate was studied for different
      calcium to phosphate (Ca/P) ratios, rotating rates, masses of balls, and
      environmental conditions. During dry grinding by ball milling, anhydrous or
      hydrated acid calcium phosphates can mechanochemically react with anhydrous or
      hydrated basic calcium salts to form dicalcium phosphate dihydrate or anhydrous,
      noncrystalline calcium phosphate, and/or calcium deficient or stoichiometric
      hydroxyapatite, depending on the Ca/P ratio in the mixture and the time of
      grinding. The reaction rate is a function of the rotation rate and the mass of
      the balls. Water is not necessary to initiate the reaction but facilitates it
      because hydrated salts react faster than the corresponding anhydrous salts.
      Neither carbon dioxide nor carbonate ions seem to have any influence on the
      transformation kinetics. The transformations that occur during grinding influence
      the final mechanical properties of hydraulic calcium phosphate cements prepared
      from these materials. Thus, if a grinding step of the starting materials is
      planed, the grinding conditions will have to be particularly well defined to
      obtain reproducible results.

PMID- 11288086
TI  - The role of crosslinking in modification of the immune response elicited against
      xenogenic vascular acellular matrices.
AB  - We have used detergent and enzymatic extraction of natural arteries to produce an
      acellular matrix vascular prosthesis (AMVP). Implanted as an allograft in a
      canine model, this AMVP shows excellent handling characteristics, low
      thromboreactivity, no evidence of aneurysm, and exceptional graft patency in the
      peripheral vasculature. As a first step in the development of xenograft AMVPs, we
      processed caprine carotid arteries to AMVP and implanted them as femoral
      interposition grafts in dogs. Explanted xenografts at 4 weeks showed multifocal
      mixed inflammatory infiltrates and focal destruction of the medial elastin in the
      inflammatory foci. To further study the immune response to xenogenic AMVP, we
      implanted canine-derived AMVPs and fresh canine arteries for 4 weeks in a Lewis
      rat model. Extraction to AMVP markedly reduced the circulating antibody response
      to the xenogenic implants; however, histological analysis revealed that both
      xenograft arteries and AMVPs produced a marked immune response with penetration
      of mononuclear cells into the media and adventitia. To modify the immune
      response, we applied three crosslinking techniques to the canine AMVPs:
      glutaraldehyde, polyglycidyl ether, and carbodiimide. All crosslinkers
      significantly reduced degradation and cellular infiltration of the prostheses.
      However, crosslinking neither eliminated the chronic inflammatory response
      surrounding the implants nor reduced the humoral response to the xenogenic
      materials.

PMID- 11288087
TI  - Ion-beam-sputtering/mixing deposition of calcium phosphate coatings. I. Effects
      of ion-mixing beams.
AB  - Ion-beam-sputtering/mixing deposition was used to produce thin calcium phosphate
      coatings on titanium substrate from the hydroxyapatite target. The mixing beam
      could be either Ar(+) or N(+) ions. It was found that as-deposited coatings were
      amorphous. No distinct peak of the hydroxyl group was observed in FTIR spectra of
      the coatings, but new spectral peaks, brought about during the deposition
      process, were present for CO(3)(2-). Scanning electron microscopy revealed that
      the deposited coatings had a uniform and dense structure. The calcium-to
      phosphorous ratio of these coatings varied between 2.0 and 3.0. Compared with the
      calcium phosphate coatings produced by Ar(+) beam-mixing deposition, the calcium
      phosphate coatings produced by N(+) beam-mixing deposition exhibited a higher
      dissolution rate in the physiologic saline solution and showed a lower
      proliferation rate of osteoblast cells.

PMID- 11288088
TI  - Dissolution response of hydroxyapatite coatings to residual stresses.
AB  - The effect of residual stress on the dissolution of hydroxyapatite (HA) coatings
      was investigated. The examined coatings of 80-, 110-, and 200-microm thickness
      were prepared by a plasma-spraying technique under identical conditions. Residual
      stresses in the coatings were measured with a hole-drilling method. Dissolution
      of the coatings was monitored along with an examination of the phase composition.
      The results showed that both tensile residual stress and amorphous HA existed
      throughout the entire depth of the coatings and tended to increase from the
      surface to the interface of the coating and substrate. The thicker the coatings
      were, the higher the maximum residual stress was. Correspondingly, the pH value
      and calcium concentration of the solutions tended to increase with the coating
      thickness. On the basis of these phenomena and a thermodynamic analysis of the
      dissolution of the HA subjected to stresses, we concluded that besides structural
      effects, residual stress was also an important intrinsic factor influencing
      dissolution of HA coatings, and the dissolution can be delayed or even restrained
      by compressive residual stress.

PMID- 11288089
TI  - Differential healing response of bone adjacent to porous implants coated with
      hydroxyapatite and 45S5 bioactive glass.
AB  - This study tested the hypothesis that the rate and the extent of bone formation
      adjacent to porous, coated Ti-6Al-4V implants are differentially affected by the
      type of bioactive ceramic coating. Forty-eight rabbits received cylindrical Ti
      6Al-4V intramedullary distal femoral implants bilaterally. Implants for the right
      limbs were coated with 45S5 Bioglass (45S5). Implants used for the left limbs
      either were coated with tricalcium phosphate/hydroxyapatite (HA) or were left
      uncoated as controls (CTL). The 45S5-coated implants histologically and
      biomechanically were compared to HA-coated and CTL implants at 4, 8, 12, and 16
      weeks. After 12 and 16 weeks of healing, more bone and thicker trabeculae were
      measured histomorphometrically within the implant pores for the 45S5-coated
      implants compared to the HA-coated and CTL implants (p < 0.05). With time the HA
      coated and CTL groups exhibited a significant decline in percent of bone and of
      trabecular thickness (p < 0.05) while the 45S5-coated implants did not.
      Biomechanical analyses indicated similar shear strengths for all treatment
      groups. In summary, 45S5-coated implants exhibited greater bone ingrowth compared
      to HA-coated and CTL implants, and they maintained their mechanical integrity
      over time.

PMID- 11288090
TI  - Immunoglobulin enhances the bioactive-glass-induced chemiluminescence response of
      human polymorphonuclear leukocytes.
AB  - Bioactive glasses are bone substitutes that chemically bind to bone. Implanted
      materials always elicit a response from surrounding tissues and thereby can
      activate inflammatory cells, with subsequent release of biomaterial and tissue
      damaging agents. Bioactive glasses can activate polymorphonuclear leukocytes
      (PMNL) and induce a release of reactive oxygen metabolites (ROM). Adsorption of
      proteins on the surface of the implanted material may influence the subsequent
      inflammatory cell response. The effect of Sandoglobulin(R) (SG) and albumin on
      the ROM release by PMNLs induced by a bioactive glass was studied by a
      chemiluminescence (CL) assay. An enhanced effect for SG and inhibitory effect for
      albumin on the CL response of PMNLs was observable. The CL response of the PMNLs
      was dependent on the incubation time of the glass in solution.

PMID- 11288091
TI  - Characterization of wollastonite-reinforced HAp--Ca polycarboxylate composites.
AB  - The effects of wollastonite on the mechanical properties and in vitro behavior of
      hydroxyapatite-Ca polyacrylate composites were studied. Powder mixtures of
      tetracalcium phosphate, poly(acrylic-co-itaconic), and wollastonite fibers (< or
      =75% by weight) were hot-pressed for 30 min at 300 degrees C and 60 kpsi. Tensile
      strengths, elastic moduli, and microstructures of the composites were
      investigated. The tensile strengths of these composites were improved by the
      addition of wollastonite fibers, whereas the elastic moduli decreased. The
      highest value of tensile strength (approximately 155 MPa) was achieved by the
      addition of 40% wollastonite. Composites were immersed in simulated body fluid
      (SBF) for up to 14 days and then in 1.5 SBF for a week. The changes in the
      concentrations of Ca, Si, and P ions and the pH of these solutions indicate
      bioactivity. An evaluation of the microstructures of the composites after SBF
      immersion indicated that apatite layers had formed on the surfaces of the
      composites.

PMID- 11288092
TI  - Mechanical strength of tooth fragment reattachment.
AB  - The aim of this study was static and fatigue test investigation of the strength
      of a tooth fragment reattached with adhesives to the tooth body. Central bovine
      incisor teeth were used, and standardized fragments were obtained by cutting the
      incisal edge of the selected teeth. All the fragments were reattached using a
      multistep dentine adhesive system, and the specimens were randomly divided into
      two groups (A and B). Group B specimens underwent a further dental treatment: a
      circumferential double chamfer prepared around the external cut interface was
      filled with light cured composite restorative resin. Static and fatigue bending
      tests were performed and linear elastic equations were used to analyze and
      compare the strength of the treated teeth. The results indicated that the static
      and fatigue bending properties were improved by using reinforcement with
      composite restorative resin.

PMID- 11288093
TI  - A new technique for measuring the cell growth and metabolism of endothelial cells
      seeded on vascular prostheses.
AB  - For the improvement of vascular graft patency, an endothelial cell (EC) lining is
      desirable. It is essential that the EC remains viable after being seeded onto the
      prosthetic graft. The aim of this study was to adapt an Alamar redox assay (ABRA)
      as a technique to monitor the viability of ECs seeded on prosthetic grafts. To
      test the graft types, we seeded human umbilical vein ECs on compliant
      polyurethane (CPU), expanded polytetrafluoroethylene, and Dacron at a density of
      2 x 10(5) cell/cm(2). After 24 h of incubation, ABRA was added, and the
      absorbance was measured at 4, 8, and 24 h. To assess seeded cell concentrations
      on grafts, we seeded CPU at densities ranging from 1 x 10(5) to 8 x 10(5)
      cell/cm(2). The validity of the test was assessed with sodium azide and mitomycin
      C, known physiological perturbators. ABRA reduction demonstrated that ECs were
      viable and functional postseeding on the prosthetic grafts. A significant
      correlation was observed with ABRA reduction and cell concentrations (p < 0.001).
      The acid phosphatase assay demonstrated enzyme activity in the cells, but they
      were not maintained under normal physiological conditions. The ABRA bioreduced
      product was soluble, stable, and noncytotoxic over 24 h. The assay is independent
      of the geometry or physiochemistry of the graft type. The technique allows the
      continuous assessment of the metabolism and viability of seeded cells, is simple
      to perform, and does not destroy the cells or graft materials.

PMID- 11288094
TI  - Study on the lubrication mechanism of natural joints by confocal laser scanning
      microscopy.
AB  - Natural joints have an excellent lubricating function, but the detailed mechanism
      is still unclear. To clarify this lubricating mechanism, we observed the behavior
      of the cartilage surface under the physiological loading condition with confocal
      laser scanning microscopy in normal and osteoarthritis (OA) cartilage rabbit
      specimens. Even with a considerable loading condition, in both natural and OA
      cartilage, the fluid pool area coexisted with the direct contact area. In the
      junction from the direct contact area to the fluid area, there was a third area
      with a liquid-crystal arrangement. In OA cartilage, these areas were generally
      irregular and small. These results suggest that a lubrication system in the fluid
      phase, such as squeeze film lubrication, might work under severe pressure in
      normal cartilage, and hyaluronic acid macromolecules in the synovial fluid might
      form a liquid-crystal structure and support pressure on the cartilage surface,
      whereas these systems did not affect the OA cartilage.

PMID- 11288095
TI  - Initial tissue response to anti-washout apatite cement in the rat palatal region:
      comparison with conventional apatite cement.
AB  - Initial tissue response to anti-washout apatite cement (aw-AC) in the palatal
      region was studied. Conventional apatite cement (c-AC) was employed as a control
      material. Bone defects generated in the rat palatal region, where complete
      hemostasis is difficult to effect, were filled with both cement types and
      examined histologically for up to 8 weeks. At 1-week postfilling, a portion of
      the c-AC had washed out, resulting in slight inflammation and severe foreign-body
      response. The degree of foreign-body response to c-AC was reduced over time;
      however, foreign-body response continued to be in evidence 8 weeks after surgery.
      As a result, poor bone formation was observed in the case of c-AC at 8 weeks post
      surgery. In contrast, aw-AC set well, maintained its shape at implantation, and
      caused little foreign-body response. Osteoblasts were observed at 2 weeks
      following surgery. Moreover, the bone defect was completely covered with new bone
      at 8 weeks post-surgery. This observation suggests that aw-AC may be used without
      complication in cases where complete hemostasis is difficult to achieve, that is,
      where the use of c-AC is contraindicated.

PMID- 11288098
TI  - Design and validation of an annular shear cell for pharmaceutical powder testing.
AB  - An annular shear cell was constructed for powder flow testing, the influence of
      design and process parameters was characterized, and the results were compared
      with other flow methods. The shear cell was designed with interchangeable parts
      to mimic other shear cells. The texture of the powder-metal interface and the gap
      distance between the lid and side wall of the trough were varied, and the effects
      of shear rate, powder bed thickness, and consolidation times were tested. Shear
      parameters, such as cohesion, angles of friction, and flow factors, were measured
      for microcrystalline cellulose, anhydrous lactose, spray-dried lactose, mannitol,
      dibasic calcium phosphate dihydrate, anhydrous theophylline, and theophylline
      monohydrate powder. The results were then compared with the Carr index, mass flow
      rate, and flowability index. Design parameters such as surface texture and the
      gap distance significantly affected the shear call results, whereas for the
      process parameters studied, the shear rate, consolidation time, and powder bed
      height had a minimal effect on the shear cell results. Of the shear parameters
      obtained, the angles of friction best represented the known flow properties of
      powders and were in general agreement with those from other flow tests.

PMID- 11288096
TI  - Influence of biomaterial surface chemistry on the apoptosis of adherent cells.
AB  - A common component of the foreign-body response to implanted materials is the
      presence of adherent macrophages that fuse to form foreign-body giant cells
      (FBGCs). These multinucleated cells have been shown to concentrate the phagocytic
      and degradative properties of macrophages at the implant surface and are
      responsible for the damage and failure of the implant. Therefore, the modulation
      of the presence or actions of macrophages and FBGCs at the material-tissue
      interface is an extensive area of recent investigations. A possible mechanism to
      achieve this is through the induction of the apoptosis of adherent macrophages,
      which results in no inflammatory consequence. We hypothesize that the induction
      of the apoptosis of biomaterial adherent cells can be influenced by the chemistry
      of the surface of adhesion. Herein, we demonstrate that surfaces displaying
      hydrophilic and anionic chemistries induce apoptosis of adherent macrophages at a
      higher magnitude than hydrophobic or cationic surfaces. Additionally, the level
      of apoptosis for a given surface is inversely related to that surface's ability
      to promote the fusion of macrophages into FBGCs. This suggests that macrophages
      fuse into FBGCs to escape apoptosis.

PMID- 11288099
TI  - Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic
      reaction producing a small amount of impurity.
AB  - A known impurity is formed in the production of a parenteral dosage form of
      diclofenac sodium if terminally sterilized by autoclave. This impurity has been
      detected as 1-(2,6-dichlorophenyl) indolin-2qone, which is also an intermediate
      from which diclofenac sodium is generally synthesized. It is only the condition
      of the autoclave method (i.e., 123 +/- 2 degrees C) that enforces the
      intramolecular cyclic reaction of diclofenac sodium forming the indolinone
      derivative and sodium hydroxide. The formation of this impurity has been found to
      depend on the initial pH of the formulation. The reaction follows first-order
      kinetics, and the energy of activation is 5.34 kcal/mol. The other excipients in
      the formulation do not have a role in this reaction. The concentration of the
      impurity in the resultant product in the ampule goes beyond the limit of the raw
      materials in the pharmacopoeias. It is thus preferable to use an alternative
      sterilization method; that is, an aseptic filtration method in which the
      formation of this impurity can be avoided.

PMID- 11288100
TI  - Theoretical description of transdermal transport of hydrophilic permeants:
      application to low-frequency sonophoresis.
AB  - Application of ultrasound enhances transdermal transport of drugs (sonophoresis).
      The enhancement may result from enhanced diffusion due to ultrasound-induced skin
      alteration and/or from forced convection. To understand the relative roles played
      by these two mechanisms in low-frequency sonophoresis (LFS, 20 kHz), a theory
      describing the transdermal transport of hydrophilic permeants in both the absence
      and the presence of ultrasound was developed using fundamental equations of
      membrane transport, hindered-transport theory, and electrochemistry principles.
      With mannitol as the model permeant, the role of convection in LFS was evaluated
      experimentally with two commonly used in vitro skin models- human cadaver heat
      stripped skin (HSS) and pig full-thickness skin (FTS). Our results suggest that
      convection plays an important role during LFS of HSS, whereas its effect is
      negligible when FTS is utilized. The theory developed was utilized to
      characterize the transport pathways of hydrophilic permeants during both passive
      diffusion and LFS with mannitol and sucrose as two probe molecules. Our results
      show that the porous pathway theory can adequately describe the transdermal
      transport of hydrophilic permeants in both the presence and the absence of
      ultrasound. Ultrasound alters the skin porous pathways by two mechanisms: (1)
      enlarging the skin effective pore radii, or (2) creating more pores and/or making
      the pores less tortuous. During passive diffusion, both HSS and FTS exhibit the
      same skin effective pore radii (r = 28 +/- 13 A). In contrast, during LFS, r
      within HSS is greatly enlarged (r > 125 A), whereas r within FTS does not change
      significantly (23 +/- 10 A). The observed different roles of convection during
      LFS across HSS and FTS can be attributed to the different degrees of structural
      alteration that these two types of skin undergo during LFS.

PMID- 11288101
TI  - Influence of crystal shape on the tableting performance of L-lysine
      monohydrochloride dihydrate.
AB  - The purpose of this study is to understand the influence of crystal shape on the
      tableting performance of L-lysine monohydrochloride (LMH) dihydrate, using the
      method of data analysis developed by Joiris E et al. 1998. Pharm Res 15:1122
      1130. Phase-pure crystals of LMH dihydrate, prism-shaped (S) and plate-shaped
      (T), were prepared by adjusting the composition of the crystallization solvent.
      At the same compaction pressure, T always gives stronger tablets than S, (i.e.;
      the tabletability of T is greater). The porosity of tablets from T crystals is
      always greater than that of S crystals when compressed at the same pressure,
      (i.e.; the compressibility of T is lower). The tensile strength of T tablets, at
      the same porosity, is greater than that of S tablets, (i.e.; the compactibility
      of T is greater). Therefore, the greater tabletability of T is a result of its
      better compactibility that overcomes the negative effects by its lower
      compressibility. The greater compactibility of T is related to favorable
      orientation of the slip planes in the tablet, corresponding to greater plasticity
      under load. The yield strengths of T and S crystals are essentially the same (20
      MPa). Therefore, the crystal shape influences the tableting performance but does
      not, in principle, affect the yield strength of LMH dihydrate.

PMID- 11288102
TI  - Development of a high throughput equilibrium dialysis method.
AB  - The identification of large numbers of biologically active chemical entities
      during high throughput screening (HTS) necessitates the incorporation of new
      strategies to identify compounds with drug-like properties early during the lead
      prioritization and development processes. One of the major steps in lead
      prioritization is an assessment of compound binding to plasma proteins, because
      it affects both the pharmacokinetics and pharmacodynamics of the compound in
      vivo. Equilibrium dialysis is the preferred method to determine the free drug
      fraction, because it is less susceptible to experimental artifacts. However, even
      low-volume standard equilibrium dialysis is currently not amenable to the HTS
      format. Those considerations dictate the development of a high throughput
      equilibrium dialysis device, without compromising the analytical quality of the
      data. The present paper demonstrates successful development of a 96-well format
      equilibrium dialysis plate. Plasma protein binding of three drugs, propranolol,
      paroxetine, and losartan, with low, intermediate, and high binding properties,
      respectively, were chosen for assay validation. The data indicate that the
      apparent free fraction obtained by this method correlates with the published
      values determined by the traditional equilibrium dialysis techniques.

PMID- 11288103
TI  - The influence of the incorporation of cholesterol and water on the particle size,
      bilayer thickness, melting behavior, and relative sucrose ester composition of
      reversed vesicles.
AB  - The influence of the incorporation of cholesterol and water on the particle size,
      bilayer thickness, melting behavior, and relative sucrose ester composition of
      reversed vesicles was studied. Reversed vesicles (RVs) were prepared of sucrose
      ester in silicon oil by sonication. The RVs were characterized by polarized light
      microscopy, laser diffraction, high-performance liquid chromatography, small
      angle X-ray scattering (SAXS), and differential scanning calorimetry. The
      particle size distributions of the studied dispersions were bimodal with peaks at
      5 and 0.4 microm. There was no significant difference in the sucrose ester
      composition of these two size categories of RVs. The incorporation of cholesterol
      and water had no effect on the size distribution of the RVs. The SAXS results
      showed that the RVs prepared without cholesterol and water consisted of bilayers
      with fully interdigitated alkyl chains. The incorporation of high concentrations
      of cholesterol caused a phase separation within the bilayers. The incorporation
      of water also resulted in a phase separation within the bilayers but at a lower
      cholesterol concentration. The presence of two different size classes of RVs in
      one RVs dispersion and the phase separation within the bilayers of certain
      compositions can have consequences for the application of RVs.

PMID- 11288104
TI  - Solid-supported lipid membranes as a tool for determination of membrane affinity:
      high-throughput screening of a physicochemical parameter.
AB  - Quantification of membrane affinity is an important early screening step in
      modern drug design. However, current approaches using different lipid membrane
      models usually are time-consuming or show severe experimental drawbacks. In this
      paper we describe the use of solid-supported lipid membranes (TRANSIL) as a new
      tool for the determination of membrane affinity. Eighteen pharmaceuticals
      (neutrals, acids, and bases) have been analyzed for their lipophilicity at
      physiological pH in an automated setup; phase separation of lipid and aqueous
      phase can be achieved simply by a short low-speed centrifugation or filtration.
      The membrane affinity is then calculated by quantification of the total drug
      concentration and the amount of drug remaining in the aqueous phase after
      incubation with solid-supported lipid membranes. Lipophilicity parameters relying
      on solid-supported lipid membranes correlate well with octanol-water partition
      coefficients K(ow) for neutral organic compounds (range of log K(ow) = 1.5-5, n =
      7, r = 0.93). Data acquisition with this lipid membrane model system is highly re
      producible. Even in the case of ionizable drugs, where K(ow) tends to
      underestimate membrane affinity, the latter can be correctly quantified using
      solid-supported lipid membranes: data comparison shows good agreement of the
      presented approach with established but time-consuming standardized lipid/buffer
      systems. Solid-supported lipid membranes allow a fast and reliable quantification
      of membrane affinity, enabling high-throughput screening of this physicochemical
      parameter.

PMID- 11288105
TI  - Permeation enhancement of a highly lipophilic drug using supersaturated systems.
AB  - The potential of supersaturation as a method for enhancing the membrane
      permeation of highly lipophilic compounds has been investigated using, as a model
      system, the transport of a lavendustin derivative (LAP, log K(o/w) = 5) through
      silicone membrane. Propylene glycol-water mixtures, which permitted the
      formulation of LAP at different levels of saturation, were prepared and tested
      for stability prior to conducting membrane permeation studies. The transport of
      LAP across silicone membrane from donor solutions containing the drug at
      different degrees of saturation (DS = 1-5) was evaluated by two independent
      experimental methods: (i) using attenuated total-reflectance Fourier transform
      infrared spectroscopy (ATR-FTIR) and (ii) using standard vertical diffusion cells
      followed by quantification with high-performance liquid chromatography (HPLC).
      Both methods demonstrated a linear relationship between the DS of the applied
      solution and the flux through the membrane, yielding similar values for the
      diffusion coefficients of LAP [diffusion cells, D = 1.75 ( +/- 0.16) x 10(-7)
      cm(2) s(-1) and ATR-FTIR, D = 1.42 ( +/- 0.26) x 10(-7) cm(2) s(-1)). In addition
      to the characterization of LAP permeation, ATR-FTIR spectroscopy enabled an
      examination of solvent transport across the membrane.

PMID- 11288106
TI  - Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester
      prodrugs of acyclovir.
AB  - The objective of this work was to improve nasal absorption of relatively
      impermeable small drug molecules via an amino acid prodrug approach. Acyclovir
      was selected as a model drug. L-Aspartate beta-ester, L-lysyl, and L-phenylalanyl
      esters of acyclovir were synthesized to investigate their effectiveness in
      enhancing nasal absorption of acyclovir. A stability study was conducted in
      phosphate buffer under various pH conditions at 25 and 37 degrees C. Enzymatic
      hydrolysis in rat nasal washings and plasma was conducted at 37 degrees C. A rat
      in situ nasal perfusion technique was utilized in this investigation to examine
      the rate and extent of nasal absorption of amino acid prodrugs. The remaining
      analyte concentrations in the nasal perfusate were quantitated by reversed-phase
      high-performance liquid chromatography. The results revealed that the L-lysyl and
      L-phenylalanyl esters were less stable than L-aspartate beta-ester. The stability
      of all three esters decreased with increasing pH and temperature. L-phenylalanyl
      ester is highly susceptible to plasma esterases, with an in vitro half-life 1.33
      min. The rat in situ nasal perfusion study revealed that the extent of nasal
      absorption of acyclovir, L-lysyl and L-phenylalanyl esters was not significant (p
      < 1%). L-Aspartate beta-ester was absorbed to the extent of approximately 8% over
      90 min of perfusion at an initial drug concentration of 100 microM. Nasal
      absorption of L-aspartate beta-ester of acyclovir was inhibited by L-asparagine
      but not by a dipeptide glycylsarcosine (Gly-Sar). The enhancement of acyclovir
      nasal absorption from the L-aspartate beta-ester prodrug suggests that nasal
      uptake of this prodrug probably involves an active transport system.

PMID- 11288107
TI  - VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent.
AB  - Inosine monophosphate dehydrogenase (IMPDH) is an essential rate-limiting enzyme
      in the purine metabolic pathway, catalyzing the de novo synthesis of guanine
      nucleotides required for lymphocyte proliferation. IMPDH has therefore been an
      attractive target for developing immunosuppressive drugs (e.g., CellCept and
      mizoribine). Here we describe the immunosuppressive activity of VX-497, a novel
      noncompetitive inhibitor of IMPDH. VX-497 (MW 452.5) is orally bioavailable and
      inhibits the proliferation of primary human, mouse, rat, and dog lymphocytes at
      concentrations of approximately 100 nM. The inhibitory effect of VX-497 on
      lymphocytes is reversed in the presence of exogenous guanosine, but not in the
      presence of adenosine or uridine, confirming that the antilymphocytic activity of
      VX-497 is specifically due to inhibition of IMPDH. The antiproliferative effect
      of VX-497 in cells is also reversed within 48 h of its removal. Based on
      evaluation of VX-497 in several lymphoid and nonlymphoid cells, the
      antiproliferative effect of VX-497 is observed to be most pronounced on lymphoid
      and keratinocyte cells as compared with fibroblasts. In vivo, oral administration
      of VX-497 inhibits the primary IgM antibody response in a dose-dependent manner,
      with an ED(50) value of approximately 30-35 mg/kg in mice. Single daily dosing of
      VX-497 is observed to be as effective as twice-daily dosing in this model of
      immune activation. These studies demonstrate that VX-497 is a potent, specific,
      and reversible IMPDH inhibitor that selectively inhibits lymphocyte
      proliferation.

PMID- 11288108
TI  - Cytokines influence mRNA expression of cytochrome P450 3A4 and MDRI in intestinal
      cells.
AB  - Inflammation and infection may have the potential to increase the bioavailability
      of drugs. This effect could be because of a reduced metabolism of xenobiotics in
      the liver and/or the intestines, or because of alterations in small intestinal
      permeability, mucosal flow, and expression of drug efflux transporters such as P
      glycoprotein (Pgp). To assess the impact on intestinal epithelium of some
      proinflammatory cytokines and macrophages on permeability and mRNA expression of
      CYP3A4 and MDRI (multidrug resistance, coding for Pgp), we used the Caco-2 cell
      line as a model. Exposure to proinflammatory cytokines and macrophages decreased
      the mRNA expression of CYP3A4 and increased the expression of MDR1 mRNA in the
      Caco-2 cells. In parallel, the cell layer permeability, as measured by sodium
      fluorescein flux, increased for all cytokine and macrophage treatments, whereas
      the effect on transepithelial electrical resistance (TEER) varied. Our findings
      suggest that inflammation and infection trigger several different cellular
      responses that may affect drug bioavailability; that is hampered CYP3A4
      expression, increased permeability of the epithelial cell layer, and enhanced Pgp
      mediated counteractive transport.

PMID- 11288109
TI  - P-glycoprotein efflux pump expression and activity in Calu-3 cells.
AB  - The purpose of this work was to determine if the sub-bronchial epithelial cell
      model, Calu-3, expresses the functionally active P-glycoprotein (Pgp) efflux
      pump. Calu-3 cells express lower levels of Pgp than both Caco-2 and A549 cells as
      determined by Western Blot analysis. In Calu-3 cells, accumulation of the Pgp
      substrates rhodamine 123 (Rh123) and calcein acetoxymethyl ester (calcein-AM) was
      increased in the presence of the specific Pgp inhibitors cyclosporin A (CsA),
      vinblastine, and taxol. Significant inhibition of Pgp activity was not observed
      until after 2 h in both cell lines. The organic anion/multidrug resistance
      associated protein-1 (MRP1) inhibitors, probenecid and indomethacin, did not
      affect Rh123 accumulation, whereas an increase in calcein accumulation was
      observed by both agents. The metabolic inhibitor sodium azide decreased the
      efflux of Rh123 out of Calu-3 cells to the same degree as CsA, supporting
      inhibition of an active, efflux pathway. The basolateral-to-apical transport of
      Rh123 was significantly higher than that in the reverse direction, indicating a
      secretory pathway of efflux that was inhibited 25-fold by CsA. Basolateral-to
      apical transport of Rh123 was inhibited slightly with both MRP1 inhibitors;
      however, no significant effect of Rh123 net secretion was observed. Mixed
      inhibitor studies demonstrated that Rh123 efflux was mainly Pgp mediated. These
      results support an energy-dependent Pgp efflux pump pathway that is sensitive to
      inhibition with CsA in Calu-3 cells.

PMID- 11288110
TI  - Binding of cosalane--a novel highly lipophilic anti-HIV agent--to albumin and
      glycoprotein.
AB  - Cosalane is a potent inhibitor of HIV replication with multiple sites of action.
      The purposes of this study were to (a) determine the extent and nature of
      cosalane binding to mucin, alpha(1)-acid glycoprotein (AAG), plasma, and human
      (HSA) and bovine serum (BSA) albumin, and (b) determine the primary site(s) of
      cosalane binding to HSA. Plasma protein binding of cosalane was studied by a gel
      filtration technique. Cosalane binding to HSA was also determined in the presence
      of salicylic acid. Competitive inhibition studies were conducted using warfarin,
      digitoxin, and diazepam to determine the primary HSA binding site(s) of cosalane.
      The drug was bound extensively to HSA and BSA and required 500-550 moles to
      saturate 1 mole of protein. Stoichiometries of cosalane binding to alpha(1)-acid
      glycoprotein (AAG) and mucin were between 30 and 50 mol/mol of either
      glycoprotein. The binding isotherm deviated from a rectangular hyperbola,
      suggesting self-association of the ligand. Salicylic acid decreased cosalane
      binding to HSA by one order of magnitude. Inhibition studies of cosalane to HSA
      revealed that the compound binds primarily to warfarin site with a K(i) of 1.24
      +/- 0.24 nM. In summary, cosalane binds extensively to serum albumins and to a
      lesser extent to both AAG and mucin.

PMID- 11288111
TI  - Evaluation of prenatal diagnosis of associated congenital heart diseases by fetal
      ultrasonographic examination in Europe.
AB  - Ultrasound scans in the mid trimester of pregnancy are now a routine part of
      antenatal care in most European countries. With the assistance of Registries of
      Congenital Anomalies a study was undertaken in Europe. The objective of the study
      was to evaluate prenatal detection of congenital heart defects (CHD) by routine
      ultrasonographic examination of the fetus. All congenital malformations suspected
      prenatally and all congenital malformations, including chromosome anomalies,
      confirmed at birth were identified from the Congenital Malformation Registers,
      including 20 registers from the following European countries: Austria, Croatia,
      Denmark, France, Germany, Italy, Lithuania, Spain, Switzerland, The Netherlands,
      UK and Ukrainia. These registries follow the same methodology. The study period
      was 1996-1998, 709 030 births were covered, and 8126 cases with congenital
      malformations were registered. If more than one cardiac malformation was present
      the case was coded as complex cardiac malformation. CHD were subdivided into
      'isolated' when only a cardiac malformation was present and 'associated' when at
      least one other major extra cardiac malformation was present. The associated CHD
      were subdivided into chromosomal, syndromic non-chromosomal and multiple. The
      study comprised 761 associated CHD including 282 cases with multiple
      malformations, 375 cases with chromosomal anomalies and 104 cases with non
      chromosomal syndromes. The proportion of prenatal diagnosis of associated CHD
      varied in relation to the ultrasound screening policies from 17.9% in countries
      without routine screening (The Netherlands and Denmark) to 46.0% in countries
      with only one routine fetal scan and 55.6% in countries with two or three routine
      fetal scans. The prenatal detection rate of chromosomal anomalies was 40.3%
      (151/375 cases). This rate for recognized syndromes and multiply malformed with
      CHD was 51.9% (54/104 cases) and 48.6% (137/282 cases), respectively; 150/229
      Down syndrome (65.8%) were livebirths. Concerning the syndromic cases, the
      detection rate of deletion 22q11, situs anomalies and VATER association was
      44.4%, 64.7% and 46.6%, respectively. In conclusion, the present study shows
      large regional variations in the prenatal detection rate of CHD with the highest
      rates in European regions with three screening scans. Prenatal diagnosis of CHD
      is significantly higher if associated malformations are present. Cardiac defects
      affecting the size of the ventricles have the highest detection rate. Mean
      gestational age at discovery was 20-24 weeks for the majority of associated
      cardiac defects.

PMID- 11288112
TI  - AZFc deletion detected in a newborn with prenatally diagnosed Yq deletion.
AB  - A case of prenatally diagnosed Yq deletion is described. Fluorescence in situ
      hybridisation (FISH) was used to identify the abnormal chromosome and to exclude
      mosaicism. Based on the cytogenetic result and the ultrasound investigation the
      pregnancy was continued. A newborn with normal male genitalia was delivered.
      Microdeletion analysis of the Yq showed the absence of the AZFc region. This type
      of deletion has been described as being associated with azoospermia or
      oligozoospermia with a progressive decrease of sperm number over time. Long-term
      andrological follow-up of the newborn will be necessary with eventual
      cryoconservation of sperm at early adulthood. The present report proposes that
      AZF analysis combined with FISH has an important role in accurate genetic
      counselling in sex chromosome anomalies.

PMID- 11288113
TI  - Prenatal diagnosis of congenital nephrosis by in utero kidney biopsy.
AB  - The diagnosis of congenital nephrosis is difficult during the antepartum period.
      The combination of an elevated amniotic fluid alpha-fetoprotein, a negative
      acetylcholinesterase, and a negative ultrasound examination is highly indicative
      of congenital nephrosis; however, these findings can also be associated with a
      normal gestation. This is the first report of pathologic confirmation of
      congenital nephrosis from an in utero fetal kidney biopsy.

PMID- 11288114
TI  - Fluorescence in situ hybridization (FISH) for rapid detection of aneuploidy:
      experience in 911 prenatal cases.
AB  - Fluorescence in situ hybridization (FISH) was performed with probes specific for
      chromosomes 13, 18, 21, X and Y on 911 of 11123 (8.2%) amniotic fluid samples
      submitted to the present authors' laboratory for cytogenetic analysis over an 8
      year period. Altogether 3516 hybridizations were performed with an interpretable
      FISH result on all chromosomes requested in 884/911 (97%) of cases. An
      uninformative FISH result occurred in 44 hybridizations among 27 cases (3%). Of a
      total of 89 karyotypically proven cases with aneuploidy that might have been
      detected by FISH, the overall detection rate was 84%. An inconclusive or
      incomplete FISH result occurred in 9/89 (10%) of these proven aneuploid cases. In
      the remaining 80 informative proven aneuploid cases, correct detection of
      aneuploidy was accomplished in 75/80 (94%) of samples. A false-negative result
      occurred in the remaining 5/80 (6%) of such informative cases. Eighteen cases had
      karyotypically proven abnormalities that could not have been detected by the
      targeted FISH. Aside from these 18 cases, FISH allowed correct detection of
      normal disomy in 785/804 (98%) of such cases. An incomplete FISH result occurred
      in 18 normal disomic cases. There was a single possible 'false-positive' FISH
      result for chromosome 21. Interphase FISH analysis of uncultured amniotic fluid
      cells has been shown to be a useful laboratory tool for rapid fetal aneuploidy
      screening during pregnancy. As with all clinical laboratory diagnostic tests,
      incomplete or inconclusive results (or even interpretive errors) occur in a small
      percentage of cases. Nevertheless, FISH results accompanied by other data and by
      appropriate counseling provide clinicians and patients with valuable information
      for clinical decision-making surrounding family planning and pregnancy
      management.

PMID- 11288115
TI  - Maternal serum levels of total activin-A in first-trimester trisomy 21
      pregnancies.
AB  - Maternal serum total activin-A concentration was measured in 45 pregnancies
      affected by trisomy 21 and 493 control unaffected pregnancies at 10-14 weeks of
      gestation. In the trisomy 21 pregnancies total activin-A concentration was
      significantly higher (1.36 MoM of the unaffected pregnancies) and in 16% of cases
      the level was above the 95th centile of normal. The log10 SD for the control
      group and the trisomy 21 group were 0.17 and 0.22, respectively. The median
      pregnancy associated plasma protein-A (PAPP-A) in this trisomy 21 series was 0.49
      and for free beta-hCG was 2.05. In the trisomy group there were significant
      positive associations between total activin-A and PAPP-A (0.6071) and free beta
      hCG (0.4255). The low median difference and the high overlap in values between
      trisomic and unaffected pregnancies make total activin-A of little practical use
      in first-trimester screening for trisomy 21.

PMID- 11288116
TI  - Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent
      single intrauterine death.
AB  - To assess the role of fetal blood sampling and intrauterine transfusion in
      monochorionic (MC) multiple pregnancy complicated by single intrauterine death
      (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre
      which underwent fetal blood sampling within 24 h of death of its MC co-twin.
      Intrauterine rescue transfusion was performed in all seven anaemic fetuses
      (hematocrit; Hct < 30%) to raise the fetal Hct to > or = 40%. The rationale was
      to prevent death and/or brain injury. Two fetuses, which were severely acidaemic
      at blood sampling, died in utero within 24 h of the procedure. In two cases, the
      surviving twins manifested abnormal sonographic findings of the fetal brain 2-5
      weeks later and underwent late termination. In two cases, the pregnancies
      continued uneventfully until delivery at 35 and 40 weeks' gestation with good
      neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but
      died within 12 h. Fetuses without anaemia were not transfused and had normal
      clinical outcomes. We suggest that intrauterine rescue transfusion before the
      development of severe acidaemia in anaemic surviving MC co-twins may prevent
      fetal death, but does not necessarily prevent brain injury. Until its role
      becomes clearer, we recommend that its use be restricted to situations in which
      the parents and the local jurisdiction allow late termination as an option if
      brain injury subsequently manifests on ultrasound.

PMID- 11288117
TI  - Denaturing high-performance liquid chromatography (DHPLC)-based prenatal
      diagnosis for tuberous sclerosis.
AB  - Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1
      in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or
      the tuberin gene (TSC2). This allelic and non-allelic heterogeneity makes genetic
      counseling and prenatal diagnosis difficult, especially as a significant
      proportion of TSC cases are due to de novo mutations. For this reason the
      identification of the disease causing mutation is mandatory for accurate
      counseling, yet current mutation detection methods such as single-strand
      conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis
      (DGGE) are labor intensive with limited detection efficiency. Denaturing high
      performance liquid chromatography (DHPLC) is a high-throughput, semi-automated
      mutation detection system with a reported mutation detection rate close to 100%
      for PCR fragments of up to 800 bp. We used a recently described DHPLC assay
      allowing the efficient detection of mutations in TSC1 to analyze the DNA
      extracted from a chorion villus sample in order to perform a prenatal diagnosis
      for TSC. The fetus was found not to have inherited the deleterious mutation and
      the DHPLC diagnosis was confirmed by haplotype analysis. This represents the
      first DHPLC-based prenatal diagnosis of a genetic disease.

PMID- 11288118
TI  - An umbilical cord teratoma in a 17-week-old fetus.
AB  - A therapeutic abortion was conducted on a 17-week-old male fetus with a large
      umbilical cord teratoma associated with an exomphalos. A review of the literature
      revealed ten other cases of umbilical cord teratoma and shows that these tumors
      have a very polymorphic presentation. Four fetuses and infants died from various
      causes indicating that there is a need for close follow-up of pregnancies with
      umbilical cord teratoma.

PMID- 11288119
TI  - Deletion 15q24-26 in prenatally detected diaphragmatic hernia: increasing
      evidence of a candidate region for diaphragmatic development.
AB  - Survival of children with congenital diaphragmatic hernia (CDH) is mainly
      dependent on the extent of lung hypoplasia and the presence of additional
      congenital anomalies or chromosomal aberrations. A chromosomal deletion 15q25
      q26.2 in a fetus with prenatally diagnosed CDH and growth retardation is
      reported. Despite optimal pre- and neonatal management the baby died shortly
      after birth. There is increasing evidence that the long arm of chromosome 15, and
      especially the region 15q24 to 15q26, plays a crucial role in the development of
      the diaphragm. The finding of a deletion within 15q24-26 in a fetus with CDH has
      to be considered a predictor of poor prognosis. It is of utmost interest for
      proper parental counselling to search in fetuses with CDH for subtle chromosomal
      lesions paying special attention to chromosome 15q.

PMID- 11288120
TI  - Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH): 2
      year multi-center retrospective study and review of the literature.
AB  - Since 1993, the position of the American College of Medical Genetics (ACMG) has
      been that prenatal interphase fluorescence in situ hybridization (FISH) is
      investigational. In 1997, the FDA cleared the AneuVysion assay (Vysis, Inc.) to
      enumerate chromosomes 13, 18, 21, X and Y for prenatal diagnosis. Data is
      presented from the clinical trial that led to regulatory clearance (1379
      pregnancies) and from retrospective case review on 5197 new pregnancies. These
      studies demonstrated an extremely high concordance rate between FISH and standard
      cytogenetics (99.8%) for specific abnormalities that the AneuVysion assay is
      designed to detect. In 29 039 informative testing events (6576 new and 22 463
      cases in the literature) only one false positive (false positive rate = 0.003%)
      and seven false negative results (false negative rate = 0.024%) occurred. A
      historical review of all known accounts of specimens tested is presented (29 039
      using AneuVysion and 18 275 specimens tested with other probes). These
      performance characteristics support a prenatal management strategy that includes
      utilization of FISH for prenatal testing when a diagnosis of aneuploidy of
      chromosome 13, 18, 21, X or Y is highly suspected by virtue of maternal age,
      positive maternal serum biochemical screening or abnormal ultrasound findings.

PMID- 11288121
TI  - Prenatal diagnosis of galactose-1-phosphate uridyltransferase (GALT)-deficient
      galactosemia.

PMID- 11288122
TI  - Prenatal diagnosis of pulmonary hypoplasia.

PMID- 11288123
TI  - Prenatal evaluation of fetal neck masses in preparation for the EXIT procedure:
      the value of pulmonary Doppler ultrasonography (PDU).
AB  - Sonographic demonstration of normal tracheal diameter and breathing-related lung
      fluid flow at 30 weeks' gestation in a fetus with a giant neck mass confirmed
      patent airways, thus avoiding an EXIT procedure.

PMID- 11288124
TI  - Klippel-Trenaunay-Weber (KTW) syndrome: the use of in utero magnetic resonance
      imaging (MRI) in a prospective diagnosis.
AB  - The diagnosis of the Klippel-Trenaunay-Weber (KTW) syndrome is rarely made
      antenatally. We report the use of both ultrasound and in utero magnetic resonance
      imaging (MRI) in the prenatal diagnosis of this syndrome. This is the first
      report of the use of prenatal MRI in the diagnosis of this condition. There was
      concordance in the findings of both modalities, with limb hypertrophy, and
      multiple haemangiomata - both subcutaneous and internally - demonstrated with
      ultrasound and MRI. The patient elected to terminate the pregnancy because of
      associated oligohydramnios and a small fetal chest noted at 20 weeks. The
      postmortem examination confirmed the antenatal diagnosis.

PMID- 11288125
TI  - Increased nuchal translucency as a prenatal manifestation of congenital adrenal
      hyperplasia.
AB  - We present two cases of pregnant women with a previous history of congenital
      adrenal hyperplasia. In both cases the only abnormal feature in the initial
      pregnancy had been increased nuchal translucency at 10-14 weeks of gestation. The
      fetal karyotype was normal and a diagnosis of congenital adrenal hyperplasia was
      made after delivery. In their current pregnancies, both fetuses also had
      increased nuchal translucency and normal fetal karyotype. Diagnosis of 21
      hydroxylase deficiency was made prenatally by DNA analysis. These findings in
      four affected fetuses suggest that congenital adrenal hyperplasia should be added
      to the list of genetic anomalies associated with an increase in nuchal
      translucency.

PMID- 11288126
TI  - Prenatal diagnosis of de novo distal 11q deletion associated with sonographic
      findings of unilateral duplex renal system, pyelectasis and orofacial clefts.
AB  - In utero diagnosis of de novo distal 11q deletion associated with renal and
      orofacial malformations has not been previously described. We present a 35-year
      old pregnant woman with prenatal sonographic findings of a unilateral duplex
      renal system, pyelectasis and orofacial clefts at 20 weeks' gestation. Both
      genetic amniocentesis and postnatal cytogenetic analysis revealed de novo
      46,XX,del(11)(q23). After birth, the fetus manifested a dysmorphic phenotype
      correlated with del(11q) syndrome. Genetic marker analysis showed a paternally
      derived distal deletion of chromosome 11q and a breakpoint centromeric to
      D11S1341. The present case represents the earliest prenatal diagnosis of a duplex
      renal system, pyelectasis and an additional feature of orofacial clefts
      associated with distal 11q deletion. Prenatal sonographic detection of a duplex
      renal system, pyelectasis and orofacial clefts should warrant a careful
      assessment of fetal anatomy and prompt cytogenetic analysis looking for
      chromosomal aberrations.

PMID- 11288127
TI  - Prenatal RHD gene determination and dosage analysis by PCR: clinical evaluation.
AB  - BACKGROUND: Use of the polymerase chain reaction (PCR) for detection of the RHD
      gene can measure the RHD gene status for unborn babies at risk for hemolytic
      disease of the newborn (HDN). The occurrence of D gene variants has led to errors
      in prenatal typing. Previous reports have highlighted the danger of assigning a
      positive fetus as negative, resulting in intrauterine fetal deaths. OBJECTIVE: To
      evaluate the effectiveness of a testing strategy whereby PCR was not only
      performed to determine the presence/absence of the RHD gene, but also used to
      assess the D gene copy number (zero, one or two RHD genes) in family studies for
      at risk pregnancies. METHODS: Samples comprising maternal (57) and paternal (42)
      peripheral blood samples, amniotic fluid (64), and matching cord blood (64) were
      collected. Rhesus (Rh) serotyping was performed on all blood samples. For RHD
      genotyping, DNA was extracted from all samples except for 28 cord samples, where
      only serotyping was performed (total 199 DNA genotyping). RHD gene PCR amplified
      exon 4 and exon 7 regions of the RHD gene. The dosage of RHD gene was determined
      by comparing the intensity of the RHD gene to that of the RHCE gene. RESULTS: A
      total of 197/199 samples showed concordance between exon 4 and exon 7 PCR
      results. Two discrepant results occurred in one family: the father carried one
      normal D gene and one D gene variant where PCR was tested to be positive using
      exon 4 but negative using exon 7. One of a pair of dizygotic twins inherited this
      abnormal D gene and was mildly affected by HDN. This was correctly identified
      antenatally and the pregnancy successfully managed. The concordance rate between
      serotypes and genotypes for 135 blood samples was 100%. Amongst the family
      groups, 8/14 heterozygous fathers transmitted the D gene and 26/26 homozygous
      fathers transmitted the D gene to the babies. The concordance rate between RHD
      genotypes from amniotic fluid and Rh D serotypes from cord blood was also 100%.
      CONCLUSION: The present study demonstrates the effectiveness of using PCR in a
      clinical setting. It verifies the importance of testing more than one region of
      the gene, and also the need for a testing strategy where both maternal and
      paternal testing for RHD gene dosages are performed.

PMID- 11288128
TI  - Role of amniotic fluid interphase fluorescence in situ hybridization (FISH)
      analysis in patient management.
AB  - We retrospectively reviewed 309 amniotic fluid interphase fluorescence in situ
      hybridization (FISH) analyses performed from October 1995 to June 1999 to assess
      the role of interphase FISH in the management of patients at increased risk for
      fetal aneuploidies. Gestational age and indications for amniocentesis, clinical
      interventions after FISH results, as well as interventions after final culture
      reports were analyzed. There were 244 (79%) normal, 50 (16%) abnormal and 15 (5%)
      inconclusive FISH results. There were no false-positive or false-negative
      results, but there were nine (3%) clinically significant chromosomal
      abnormalities not detectable by FISH. Of the 50 women with abnormal FISH results,
      26 (52%) elected to terminate the pregnancy prior to the availability of the
      standard chromosome analysis. In two of the fetuses with trisomy 21 no
      abnormalities were reported by ultrasound examination. Our experience indicates
      that interphase FISH results played an important role in decision making,
      especially for pregnancies close to 24 weeks' gestation. Standard karyotype
      analysis is still required for detection of chromosome abnormalities not
      detectable by interphase FISH techniques and for clarification of unusual or
      inconclusive FISH results.

PMID- 11288129
TI  - Current awareness in prenatal diagnosis.

PMID- 11288130
TI  - Differential effects of dihalogenated and trihalogenated acetates in the liver of
      B6C3F1 mice.
AB  - Haloacetates are produced in the chlorination of drinking water in the range 10-
      100 microg l(-1). As bromide concentrations increase, brominated haloacetates
      such as bromodichloroacetate (BDCA), bromochloroacetate (BCA) and dibromoacetate
      (DBA) appear at higher concentrations than the chlorinated haloacetates:
      dichloroacetate (DCA) or trichloroacetate (TCA). Both DCA and TCA differ in their
      hepatic effects; TCA produces peroxisome proliferation as measured by increases
      in cyanide-insensitive acyl CoA oxidase activity, whereas DCA increases glycogen
      concentrations. In order to determine whether the brominated haloacetates DBA,
      BCA and BDCA resemble DCA or TCA more closely, mice were administered DBA, BCA
      and BDCA in the drinking water at concentrations of 0.2--3 g l(-1). Both BCA and
      DBA caused liver glycogen accumulation to a similar degree as DCA (12 weeks). The
      accumulation of glycogen occurred in cells scattered throughout the acinus in a
      pattern very similar to that observed in control mice. In contrast, TCA and low
      concentrations of BDCA (0.3 g l(-1)) reduced liver glycogen content, especially
      in the central lobular region. The high concentration of BDCA (3 g l(-1))
      produced a pattern of glycogen distribution similar to that in DCA-treated and
      control mice. This effect with a high concentration of BDCA may be attributable
      to the metabolism of BDCA to DCA. All dihaloacetates reduced serum insulin
      levels. Conversely, trihaloacetates had no significant effects on serum insulin
      levels. Dibromoacetate was the only brominated haloacetate that consistently
      increased acyl-CoA oxidase activity and rates of cell replication in the liver.
      These results further distinguish the effects of the dihaloacetates from those of
      peroxisome proliferators like TCA.

PMID- 11288131
TI  - Use of methyl salicylate as a simulant to predict the percutaneous absorption of
      sulfur mustard.
AB  - Exposure to chemical vesicants such as sulfur mustard (HD) continues to be a
      threat to military forces requiring protectant strategies to exposure to be
      evaluated. Methyl salicylate (MS) has historically been the simulant of choice to
      assess HD exposure. The purpose of this study was to compare the percutaneous
      absorption and skin deposition of MS to HD in the isolated perfused porcine skin
      flap (IPPSF). The HD data were obtained from a previously published study in this
      model wherein 400 microg cm(-2) of ](14)C[-MS or ](14)C[-HD in ethanol were
      topically applied to 16 IPPSFs and experiments were terminated at 2, 4 or 8 h.
      Perfusate was collected at increasing time intervals throughout perfusion.
      Radioactivity was determined in perfusate and skin samples. Perfusate flux
      profiles were fitted to a bi-exponential model Y(t) = A(e(-bt) - e(-dt)) and the
      area under the curve (AUC), peak flux and time to peak flux were determined.
      Sulfur mustard had more pronounced and rapid initial flux parameters (P < 0.05).
      The AUCs determined from observed and model-predicted parameters were not
      statistically different, although the mean HD AUC was 40--50% greater than MS.
      The HD skin and fat levels were up to twice those seen with MS, but had lower
      stratum corneum and residual skin surface concentrations (P < 0.05). Compared
      with other chemicals studied in this model, HD and MS cutaneous disposition were
      very similar, supporting the use of MS as a dermal simulant for HD exposure.

PMID- 11288132
TI  - Combined pulmonary toxicity of cadmium chloride and sodium
      diethyldithiocarbamate.
AB  - The pulmonary toxicity of sodium diethyldithiocarbamate and cadmium chloride,
      each separately and in combination, was compared in Sprague-Dawley rats after
      single intratracheal instillation in sequential experiments by chemical,
      immunological and morphological methods. With combined exposure, the cadmium
      content of the lungs increased permanently relative to that of the lungs of just
      cadmium-treated animals. Immunoglobulin levels of the whole blood did not change,
      whereas in bronchoalveolar lavage the IgA and IgG levels increased significantly.
      Morphological changes were characteristic of the effects of cadmium but were more
      extensive and more serious than in the case of cadmium administration alone: by
      the end of the first month, interstitial fibrosis, emphysema and injury of
      membranes of type I pneumocytes developed and hypertrophy and loss of microvilli
      in type II pneumocytes were detectable. These results showed that although
      dithiocarbamates as chelating agents are suitable for the removal of cadmium from
      organisms, they alter the redistribution of cadmium within the organism, thereby
      increasing the cadmium content in the lungs, and structural changes are more
      serious than observed upon cadmium exposure alone.

PMID- 11288133
TI  - Polarized light scattering as a rapid and sensitive assay for metal toxicity to
      bacteria.
AB  - A new method that utilizes the scattering of polarized light from a suspension of
      bacteria to assay the effect of toxins is evaluated. The method compares the time
      dependence of changes in an angular scattering pattern obtained from a suspension
      of Escherichia coli bacteria with no toxin exposure to the corresponding, but
      reduced, changes that occur when there is exposure to a small concentration of
      certain toxicants. The changes are due to growth of a specially prepared
      population of these bacteria. The changes in the pattern normally reflect a
      change in average bacterial size due to growth, whereas the reduction of the
      change in pattern occurs when there is rapid cessation of bacterial growth. The
      method was tested with varying concentrations of the ions of five different heavy
      metals. The results using this method during the first few minutes after exposure
      to the toxicant were compared to the relative survival of colony-forming units of
      the bacteria. The graphs for the two methods were found to be approximately
      parallel for each of the five metals examined. This result indicates that the
      toxic effect of these metals takes place relatively quickly for these bacteria.
      These results were compared with results available from the literature for the
      same metals but using other methods for measuring the toxicity to bacteria.
      Published in 2001 by John Wiley & Sons Ltd.

PMID- 11288134
TI  - Allergen-induced changes in interleukin 1 beta (IL-1 beta) mRNA expression by
      human blood-derived dendritic cells: inter-individual differences and relevance
      for sensitization testing.
AB  - The development of in vitro methods for the identification of skin sensitizers
      based upon analysis of Langerhans cell (LC) function has been constrained by the
      fact that these cells represent only a minority population in the skin that, once
      isolated, alter their phenotype spontaneously and rapidly. Methods have been
      developed recently that allow the expansion in culture using appropriate cytokine
      conditions of LC-like dendritic cells (DCs) from certain tissues, including human
      peripheral blood. It has been demonstrated that culture of human blood-derived LC
      like cells with selected potent contact allergens such as 2,4
      dinitrofluorobenzene (DNFB) stimulates selective phenotypic changes, including
      the up-regulation of interleukin 1 beta (IL-1 beta) mRNA expression, under
      conditions where skin irritants are without effect. However, in our own previous
      investigations, we have observed that there appear to be differences between
      blood donors with respect to the responsiveness of DCs to DNFB-induced changes in
      IL-1 beta expression, differences that could compromise the utility of this
      approach as a screening method for contact allergens. We have therefore
      investigated donor variability in DC responsiveness to a panel of known human
      contact allergens (DNFB; paraphenylene diamine, PPD; methyl-
      chloroisothiazolinone/methylisothiazolinone, CMIT), to the skin irritant
      benzalkonium chloride and to the mitogen phorbol myristate acetate (PMA).
      Dendritic cells derived from all donors expressed IL-1 beta mRNA constitutively.
      Treatment of DCs isolated from donors with a responder phenotype to DNFB with PPD
      or CMIT resulted also in up-regulation of IL-1 beta mRNA expression, although
      such changes were always comparatively modest, generally resulting in a twofold
      induction compared with vehicle-treated controls. Dendritic cells derived from
      donors with a non-responder phenotype to DNFB failed also to respond to these
      additional contact allergens under conditions where the mitogen PMA caused
      similar increases in IL-1 beta expression to those observed for allergen
      responsive donors. Benzalkonium chloride failed to provoke changes in the
      expression of this cytokine in any donor examined, irrespective of their
      responder phenotype. The temporal stability of the responder/non-responder DC
      phenotype was confirmed, with stable phenotypes with respect to DNFB-induced
      changes in IL-1 beta mRNA expression observed over a period of some 18 months.
      Fifty per cent (6/12) of donors tested over this period displayed a responder
      phenotype. These data demonstrate that chemical allergens do stimulate consistent
      changes in IL-1 beta mRNA expression in the proportion of donors who have a
      responsive phenotype, and that such responses are apparently selective for
      allergen using the relatively narrow range of materials assessed to date.
      However, the modest response to very strong contact allergens, coupled with the
      difficulties of responder/non-responder phenotypes, means that in its present
      form this approach does not lend itself to the routine assessment of skin
      sensitizing activity.

PMID- 11288135
TI  - Expression of cytochrome P-450s and glutathione S-transferases in the rat liver
      during water deprivation: effects of glucose supplementation.
AB  - Pharmacokinetic profiles of therapeutic agents change in dehydrated animals. The
      present study was designed to determine the expression of xenobiotic-metabolizing
      enzymes in the rat liver and the effect of glucose supplementation during water
      deprivation. Deprivation of water intake, which reduced food intake, resulted in
      no significant change in the cytochrome P-450 1A2, 2B1/2, 2C11 and 3A1/2
      expression. Cytochrome P-450 2E1, however, was three-fold induced with an
      increase in the mRNA. Rehydration of 48-h water-deprived rats for the next 24 h
      with free access to foods restored the P-450 2E1 level to that of the control,
      although rehydration with 20% food supply failed to normalize the P-450 2E1
      expression. Water deprivation caused a reduction in the plasma insulin level,
      which was prevented by rehydration with a sufficient food supply. The plasma
      insulin level was inversely related to the P-450 2E1 expression. Glucose feeding
      instead of foods during dehydration prevented P-450 2E1 induction in the absence
      of recovering the plasma insulin level. Western blot analysis revealed that the
      hepatic rGSTA2 level was 30% decreased in dehydrated rats, whereas the rGSTA3, M1
      and M2 expression was not affected. Suppression of rGSTA2 accompanied a reduction
      in the mRNA. Glucose feeding further reduced rGSTA2 expression. The data
      indicated that expression of major P-450s and glutathione S-transferases, except
      P-450 2E1, was not greatly affected by water deprivation and that the P-450 2E1
      induction and a decrease in plasma insulin resulted from the reduction in food
      intake but not from dehydration per se. Glucose supplementation restored P-450
      2E1 expression but further suppressed rGSTA2 expression during water deprivation.

PMID- 11288136
TI  - Toxicological, medical and industrial hygiene aspects of glutaraldehyde with
      particular reference to its biocidal use in cold sterilization procedures.
AB  - Aqueous solutions of > or =5% glutaraldehyde (GA) are of moderate acute peroral
      toxicity and those of < or =2% are of slight toxicity. By single sustained skin
      contact, aqueous GA solutions of > or =45% are of moderate acute percutaneous
      toxicity, those of 25% are of slight toxicity and those of </=15% do not present
      an acute percutaneous hazard. Vapor generated at ambient temperature may cause
      sensory irritant effects to the eye and respiratory tract, but not acute
      respiratory tract injury. The 50% decrease in respiratory rate (rd(50)) is 13.86
      ppm. A 0.1% solution of GA is not irritating to the eye; the threshold for
      conjunctival irritation is 0.2% and for corneal injury it is 1.0%. Eye injury is
      moderate at 2% and severe at > or =5%. Primary skin irritation depends on the
      duration and contact site, occlusion and solvent. By sustained contact, the
      threshold for skin irritation is 1%, above which erythema and edema are dose
      related. With 45% and higher, skin corrosion may occur. There is a low incidence
      of skin sensitizing reactions, with an eliciting threshold of 0.5% aqueous GA.
      However, GA is neither phototoxic nor photosensitizing. Subchronic repeated
      exposure studies by the peroral route show only renal physiological compensatory
      effects, secondary to reduced water consumption. Repeated skin contact shows only
      minor skin irritant effects without systemic toxicity. By subchronic vapor
      exposure, effects are limited to the nasal mucosa at 1.0 ppm, with a no-effect
      concentration generally at 0.1 ppm. There is no evidence for systemic target
      organ or tissue toxicity by subchronic repeated exposure by any route. A chronic
      drinking water study showed an apparent increase, in females only, of large
      granular cell lymphocytic leukemia but this was not dosage related. This is most
      likely the result of a modifying effect on the factor(s) responsible for the
      expression of this commonly occurring rat neoplasm. A chronic (2-year) inhalation
      toxicity/oncogenicity study showed inflammatory changes in the anterior nasal
      cavity but no neoplasms or systemic toxicity. In vitro genotoxicity studies-
      bacterial mutagenicity, forward gene mutation (HGPRT and TK loci), sister
      chromatid exchange, chromosome aberration, UDS and DNA repair tests--have given
      variable results, ranging from no effect through to weak positive. In vivo
      genotoxicity studies--micronucleus, chromosome aberration, dominant lethal and
      Drosophila tests--generally have shown no activity but one mouse intraperitoneal
      study showed bone marrow cell chromosome aberrations. Developmental toxicity
      studies show GA not to be teratogenic, and a two-generation study showed no
      adverse reproductive effects. Percutaneous pharmacokinetic studies showed low
      skin penetration, with lowest values measured in vitro in rats and human skin.
      Overexposure of humans produces typical sensory irritant effects on the eye, skin
      and respiratory tract. Some reports have described an asthmatic-like reaction by
      overexposure to GA vapor. In most cases this resembles reactive airways
      dysfunction syndrome, and the role of immune mechanisms is uncertain. Local
      mucosal effects may occur if medical instruments or endoscopes are not adequately
      decontaminated. Protection of individuals from the potential adverse effects of
      GA exposure requires that there be adequate protection of the skin, eyes and
      respiratory tract. The airborne concentration of GA vapor should be kept below
      the recommended safe exposure level (e.g. the threshold limit value) by the use
      of engineering controls. Those who work with GA should, through a training
      program, be aware of the properties of GA, its potential adverse effects, how to
      handle the material safely and how to deal with accidental situations involving
      GA. If effects develop in exposed workers, the reasons should be determined
      immediately and corrective methods initiated. (c) 2001 John Wiley & Sons, Ltd.

PMID- 11288137
TI  - Cytokine fingerprinting and hazard assessment of chemical respiratory allergy.
AB  - Allergic sensitization of the respiratory tract resulting in occupational asthma
      and other symptoms can be caused by a variety of chemicals and represents an
      important occupational health problem. Although there is a need to identify and
      characterize those chemicals that are able to cause respiratory allergy, there
      are currently no well validated or widely accepted predictive test methods. Some
      progress has been made with guinea pig assays, but our attention in this
      laboratory has focused instead on the development of novel approaches based on an
      understanding of the nature of immune responses induced in mice by chemical
      allergens. We have shown that whereas contact allergens provoke in mice selective
      type 1 immune responses, characterized by the secretion by draining lymph node
      cells (LNC) of high levels of the cytokine interferon gamma (IFN-gamma), chemical
      respiratory allergens stimulate instead preferential type 2 responses associated
      with comparatively high levels of interleukins 4 and 10 (IL-4 and IL-10). The
      divergent immune responses provoked by different classes of chemical allergens,
      and the phenotypes of selective cytokine secretion that characterize such
      responses, form the basis of a novel method-cytokine fingerprinting--that permits
      chemicals that have the potential to cause respiratory allergy to be identified
      and distinguished from those that are associated primarily with contact
      sensitization. In this article the immunobiological basis for cytokine
      fingerprinting is considered and the development, evaluation and practical
      application of the assay are reviewed.

PMID- 11288138
TI  - 2,4-Pentanedione.

PMID- 11288139
TI  - Nitric oxide and nitric oxide synthase in Huntington's disease.
AB  - Nitric oxide (NO) is a biologically active inorganic molecule produced when the
      semiessential amino acid l-arginine is converted to l-citrulline and NO via the
      enzyme nitric oxide synthase (NOS). NO is known to be involved in the regulation
      of many physiological processes, such as control of blood flow, platelet
      adhesion, endocrine function, neurotransmission, neuromodulation, and
      inflammation, to name only a few. During neuropathological conditions, the
      production of NO can be either protective or toxic, dependent on the stage of the
      disease, the isoforms of NOS involved, and the initial pathological event. This
      paper reviews the properties of NO and NOS and the pathophysiology of
      Huntington's disease (HD). It discusses ways in which NO and NOS may interact
      with the protein product of HD and reviews data implicating NOS in the
      neuropathology of HD. This is followed by a synthesis of current information
      regarding how NO/NOS may contribute to HD-related pathology and identification of
      areas for potential future research.

PMID- 11288140
TI  - NID67, a small putative membrane protein, is preferentially induced by NGF in
      PC12 pheochromocytoma cells.
AB  - In an effort to identify genes involved in neuronal differentiation, we have used
      representational difference analysis (RDA) to clone cDNAs that are preferentially
      induced by nerve growth factor (NGF) vs. epidermal growth factor (EGF) in PC12
      pheochromocytoma cells. We now report the cloning of a previously unknown primary
      response gene, NID67. In addition to a robust induction by NGF and FGF, both of
      which cause PC12 cells to differentiate, NID67 is strongly induced by forskolin,
      A23187 and ATP. EGF, TPA and KCl induce NID67 only weakly. NID67 mRNA is most
      abundant in heart, ovary and adrenal. Modest levels are present in most brain
      regions, testis, thyroid, thymus, pituitary, kidney and intestine; little NID67
      is present in skeletal muscle and cerebellum. The NID67 cDNA contains a 180 bp
      open reading frame (ORF) that encodes a 60 amino acid protein. The central 29
      amino acids are very hydrophobic and very likely comprise a transmembrane domain.
      Mouse and human NID67 cDNAs contain an ORF similar to NID67; the rat and human
      protein sequences are 85% identical whereas the rat and mouse sequences are 92%
      identical. In vitro transcription and translation reactions confirmed that the
      ORF we identified produces a 6000 Da protein product. Several small membrane
      proteins are similar to NID67; they contain a transmembrane domain and little
      more. All of these proteins participate in forming or regulating ion channels.
      NID67 may play a similar role in cellular physiology.

PMID- 11288141
TI  - TNF-alpha stimulates caspase-3 activation and apoptotic cell death in primary
      septo-hippocampal cultures.
AB  - Primary septo-hippocampal cell cultures were incubated in varying concentrations
      of tumor necrosis factor (TNF-alpha; 0.3-500 ng/ml) to examine proteolysis of the
      cytoskeletal protein alpha-spectrin (240 kDa) to a signature 145 kDa fragment by
      calpain and to the apoptotic-linked 120-kDa fragment by caspase-3. The effects of
      TNF-alpha incubation on morphology and cell viability were assayed by fluorescein
      diacetate-propidium iodide (FDA-PI) staining, assays of lactate dehydrogenase
      (LDH) release, nuclear chromatin alterations (Hoechst 33258), and
      internucleosomal DNA fragmentation. Incubation with varying concentrations of TNF
      alpha produced rapid increases in LDH release and nuclear PI uptake that were
      sustained over 48 hr. Incubation with 30 ng/ml TNF-alpha yielded maximal, 3-fold,
      increase in LDH release and was associated with caspase-specific 120-kDa fragment
      but not calpain-specific 145-kDa fragment as early as 3.5 hr after injury.
      Incubation with the pan-caspase inhibitor, carbobenzosy- Asp-CH(2)-OC (O)-2-6
      dichlorobenzene (Z-D-DCB, 50-140 microM) significantly reduced LDH release
      produced by TNF-alpha. Apoptotic-associated oligonucleosomal-sized DNA
      fragmentation on agarose gels was detected from 6 to 72 hr after exposure to TNF
      alpha. Histochemical changes included chromatin condensation, nuclear
      fragmentation, and formation of apoptotic bodies. Results of this study suggest
      TNF-alpha may induce caspase-3 activation but not calpain activation in septo
      hippocampal cultures and that this activation of caspase-3 at least partially
      contributes to TNF-alpha-induced apoptosis.

PMID- 11288142
TI  - Expression of mouse igf2 mRNA-binding protein 3 and its implications for the
      developing central nervous system.
AB  - Functional analyses of neural RNA-binding proteins have focused mainly on their
      roles as modulators of posttranscriptional gene regulation, e.g., alternative
      splicing, dendritic mRNA localization, and local translation. Here we identified
      a mouse homologue of human IMP3, which is known to bind to and repress the
      translation of igf2 leader 3 mRNA. The mouse igf2 mRNA-binding protein 3 (mIMP3)
      is a member of the zipcode binding protein-1 (ZBP-1) family previously reported
      in chick fibroblast cells. mIMP3 was expressed in undifferentiated
      neuroepithelial cells and some postmitotic neurons at early embryonic stages
      (E10.5--E12.5), and its expression level decreased after the midembryonic stage
      (E12.5) until birth. The expression profile of mIMP3 is very similar to that of
      mouse igf2 leader 3 mRNA. In vitro UV cross-linking experiments showed that mIMP3
      preferentially bound to igf2 leader 3 mRNA rather than igf2 leader 4 mRNA and did
      not bind the zipcode region of beta-actin or c-myc mRNA. Furthermore, persistent
      expression of mIMP3 protein in an undifferentiated P19 cell line revealed that
      mIMP3 inhibited neuronal differentiation morphologically and
      immunohistochemically. Taken together, these observations raise the possibility
      that mIMP3 represses neuronal differentiation through the regulation of igf2 mRNA
      expression.

PMID- 11288144
TI  - Cell death in the superficial dorsal horn in a model of neuropathic pain.
AB  - The aims of this study were to investigate the occurrence of apoptotic cell death
      in the dorsal horn of the adult rat spinal cord following chronic constriction
      injury (CCI) to the sciatic nerve and to correlate this with behavioural
      responses. Six groups of six rats were used as follows: 1) CCI, 2) CCI, 3) MK801
      + CCI, 4) axotomy, 5) sham, and 6) naive. Group 1 animals were behaviourally
      tested for thermal hyperalgesia 8 days following surgery and sacrificed and the
      spinal cords removed and frozen. The rest of the groups underwent the same
      procedure 14 days following surgery. The lumbar region of the spinal cord was
      cryosectioned and the incidence of apoptotic cells investigated using the TUNEL
      technique plus Hoechst double labelling. By 8 days post-CCI, hyperalgesia had
      developed in the ipsilateral paw, which was still present 14 days after the
      injury compared to the contralateral paw and naive and sham animals. Preemptive
      MK-801 prevented the onset of hyperalgesia. Significant numbers of apoptotic
      cells were present in the ipsilateral dorsal horn of the spinal cord 8 and 14
      days following CCI compared to the contralateral side and to naive and sham
      animals. Preemptive treatment with MK-801 reduced the extent of apoptosis
      resulting from CCI to the level seen in control animals. This study demonstrates
      that cells undergo apoptosis as a result of CCI simultaneous with the occurrence
      of hyperalgesia. Furthermore, MK-801 prevents the onset of hyperalgesia and
      reduces the extent of apoptotic cell death, suggesting, perhaps, that apoptosis
      contributes to the initiation/maintenance of hyperalgesia.

PMID- 11288143
TI  - Neurons and glial cells of the embryonic human brain and spinal cord express
      multiple and distinct isoforms of laminin.
AB  - We have identified by immunocytochemistry, Western blotting, and RT-PCR the
      isoforms of laminin expressed by glial cells and neurons cultured from human
      embryonic brain and spinal cord. We show that most of the known laminins are
      present in human neurons and glial cells. Importantly, Western analysis
      demonstrates that the isoforms of laminin present in embryonic human brain differ
      from those expressed in human spinal cord. Neurons of the brain and spinal cord
      also express their distinct and characteristic isoforms of laminin compared to
      the glial cells of the same CNS regions. These results suggest that, in addition
      to the known laminins, several novel isoforms may exist in the human embryonic
      CNS. The observed differences between the isoforms of laminin in brain and spinal
      cord neurons and glial cells may result from primary structural changes or from
      posttranslational modifications, e.g., variations in glycosylation. Thus,
      identification of these novel laminins and determination of their function(s)
      should further our understanding of the mechanisms of aging, disease, and trauma
      in the human CNS.

PMID- 11288145
TI  - Adenosine triphosphate and diadenosine pentaphosphate induce [Ca(2+)](i) increase
      in rat basal ganglia aminergic terminals.
AB  - Synaptosomal preparations from rat midbrain exhibit specific responses to both
      ATP and Ap(5)A, which stimulate a [Ca(2+)](i) increase in the presynaptic
      terminals via specific ionotropic receptors, termed P2X, and diadenosine
      polyphosphate receptors. Aminergic terminals from rat brain basal ganglia were
      characterized by immunocolocalization of synaptophysin and the vesicular
      monoamine transporter VMAT2 and represent 29% of the total. These aminergic
      terminals respond to ATP and/or Ap(5)A with an increase in the intrasynaptosomal
      calcium concentration as measured by a microfluorimetric technique. This
      technique, which allows single synaptic terminals to be studied, showed that
      roughly 8.2% +/- 1.6% of the aminergic terminals respond to ATP, 16.9% +/- 1.3%
      respond to Ap(5)A, 32.6% +/- 0.8% to both, and 42.3% +/- 1.5% of them have no
      response. Immunological studies performed with antibodies against ionotropic ATP
      receptor subunits showed positive labelling with anti-P2X(3) antibodies in 39% of
      the terminals. However, colocalization studies of VMAT and P2X(3) receptor
      subunit indicate that only 25% of the aminergic terminals also contain this
      receptor subtype. These results demonstrate that the aminergic terminals from the
      rat brain basal ganglia are to a large extent under the modulation of presynaptic
      nucleotide and dinucleotide receptors.

PMID- 11288146
TI  - Elevated vulnerability to oxidative stress-induced cell death and activation of
      caspase-3 by the Swedish amyloid precursor protein mutation.
AB  - The Swedish double mutation (KM670/671NL) of amyloid precursor protein (APPsw) is
      associated with early-onset familial Alzheimer's disease (FAD) and results in
      from three- to sixfold increased beta-amyloid production. The goal of the present
      study was to elucidate the effects of APPsw on mechanisms of apoptotic cell
      death. Therefore, PC12 cells were stably transfected with human APPsw. Here we
      report that the vulnerability of APPsw-bearing PC12 cells to undergo apoptotic
      cell death was significantly enhanced after exposure to hydrogen peroxide
      compared to human wild-type APP-bearing cells, empty vector-transfected cells,
      and parent untransfected cells. In addition, we have analyzed the potential
      influence of several mechanisms that can interfere with the execution of the
      apoptotic cell death program: the inhibition of cell death by the use of caspase
      inhibitors and the reduction of oxidative stress by the use of (+/-)-alpha
      tocopherol (vitamin E). Interestingly, oxidative stress-induced cell death was
      significantly attenuated in APPsw PC12 cells by pretreatment with caspase-3
      inhibitors but not with caspase-1 inhibitors. In parallel, caspase-3 activity was
      markedly elevated in APPsw PC12 after stimulation with hydrogen peroxide for 6
      hr, whereas caspase-1 activity was unaltered. In addition, oxidative stress
      induced cell death could be reduced after pretreatment of APPsw cells with (+/-)
      alpha-tocopherol. The protective potency of (+/-)-alpha-tocopherol was even
      greater than that of caspase-3 inhibitors. Our findings further emphasize the
      role of mutations in the amyloid precursor protein in apoptotic cell death and
      may provide the fundamental basis for further efforts to elucidate the underlying
      processes caused by FAD-related mutations.

PMID- 11288147
TI  - Altered expression of glutamate transporters under hypoxic conditions in vitro.
AB  - Regulation of extracellular excitotoxins by glial and neuronal glutamate
      transporters is critical to maintain synaptic terminal integrity. Factors
      interfering with the normal functioning of these transporters might be involved
      in neurodegeneration. Among them, recent studies have shown that hypoxia alters
      glutamate transporter function; however, it is unclear if hypoxia has an effect
      on the expression of glutamate transporters and which intracellular signaling
      pathways are involved. The C6 rat glial and GT1--7 mouse neuronal cell lines were
      exposed to hypoxic conditions (5% CO(2), 95% N(2)) and levels of glutamate
      transporter mRNA were determined by ribonuclease protection assay. After 21 hr,
      there was a 100% increase in levels of rat excitatory amino acid transporter 3
      (EAAT3) mRNA in C6 cells and a 600% increase in levels of murine EAAT2 mRNA in
      GT1--7 cells. There was a similar increase in mRNA levels after hypoxia in C6
      cells transfected with human EAAT2, whereas reoxygenation normalized the
      expression levels of glutamate transporters. Although the expression of EAATs was
      associated with increased immunoreactivity by Western blot, functioning of the
      transporters was decreased as evidenced by D-aspartate uptake. Finally, although
      the protein kinase C stimulator phorbol-12-myristate-13-acetate enhanced EAAT2
      mRNA levels after hypoxia, protein kinase C inhibitor bisindolylmaleimide I had
      the opposite effect. Taken together, this study suggests that the hypoxia is
      capable of upregulating levels of EAATs via a protein kinase C-dependent
      compensatory mechanism. This increased expression is not sufficient to overcome
      the decreased functioning of the EAATs associated with decreased ATP production
      and mitochondrial dysfunction.

PMID- 11288148
TI  - Glutamyl cysteine synthetase catalytic and regulatory subunits localize to
      dopaminergic nigral neurons as well as to astrocytes.
AB  - Glutathione (GSH) is considered one of the primary antioxidant compounds in the
      brain, important for the removal of peroxides from this organ. GSH levels have
      been reported to be significantly lower in the substantia nigra (SN) of Parkinson
      patients vs. age-matched controls. Curiously, GSH has been proposed to be present
      in brain astrocytes rather than in neurons even though these cells are not lost
      in Parkinson disease. We report that the catalytic and regulatory subunit
      proteins of glutamyl cysteine synthetase (GCS), the primary enzyme involved in
      GSH synthesis, are present not only in astrocytes but also in dopaminergic
      neurons of the SN. This may have important implications in terms of GSH loss
      associated with Parkinson disease.

PMID- 11288149
TI  - Effect of endogenous beta-hydroxybutyrate on glucose metabolism in the diabetic
      rabbit brain: a (13)C-magnetic resonance spectroscopy study of [U-(13)C]glucose
      metabolites.
AB  - The neurological consequences of diabetes mellitus have recently been receiving
      greater attention in both clinical and experimental settings. The deleterious
      effect of hyperglycemia and altered oxidative substrate availability on the
      diabetic brain is the subject of many studies. The aim of the present study was
      to examine the effect of the altered metabolic environment, namely, hyperglycemia
      and hyperketonemia, on glucose metabolism in the diabetic brain. More
      specifically, we examined the effect of diabetes on the glucose flux via the
      pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) pathways and
      subsequent metabolism in the tricarboxylic acid cycles in neurons and glia. To
      this end, [U-(13)C]glucose was infused into the circulation of alloxan-induced
      diabetic young adult rabbits, and the [(13)C]glucose metabolites were
      subsequently studied in brain extracts by (13)C-NMR. Significantly elevated brain
      glucose levels were found. In the hyperketonemic rabbits, elevated cerebral
      levels of beta-hydroxybutyrate (beta-HBA) were found. Alterations in the labeling
      patterns of glutamine in the hyperketonemic group lead to the conclusion that the
      elevated beta-HBA levels inhibit glucose metabolism, mostly in glia. This results
      in accumulation of glucose in the diabetic brain. In addition, altered levels of
      glutamine, glutamate, and GABA were also attributed to the effect of beta-HBA on
      brain metabolism. The possible role of these metabolic perturbations in causing
      neurological damage remains to be investigated.

PMID- 11288150
TI  - Multifactorial effects on the patency rates of forearm arterial repairs.
AB  - It is clear that the late clinical symptomatology and the patency of forearm
      arterial repairs have been contradictory. This study, during which the
      relationship between the symptomatology and patency has been studied, explores
      the influence of the local hemodynamic changes and the effect of microsurgical
      technique on patency rates. Thirty-five patients with a total of 44 arterial
      injuries were treated. Hemodynamic studies were done intraoperatively, and all
      patients were evaluated postoperatively with a neurologic, vascular, clinical
      examination and by radiodiagnostic methods. An overall patency of 77.2% was
      found. Color-Doppler ultrasonography (CDU) failed by 14.2% as compared with
      angiography, which did not fail. High blood pressure on the distal stump led to
      significantly reduced patency rates. Eight patients without nerve problems were
      found to be symptomatic as a result of the poor patency rate. Many factors are
      observed to influence patency rate. The nonpatent forearm artery can be
      symptomatic in anatomically and hemodynamically varied hands. CDU was more
      reliable for hemodynamic evaluation; conversely, angiography was more dependable
      for arterial morphology. The results of this study suggest that to correlate the
      clinical symptomatology and the patency rates, all arterial repairs should be
      assessed both clinically and radiodiagnostically.

PMID- 11288151
TI  - Experimental study of vascularized nerve graft: evaluation of nerve regeneration
      using choline acetyltransferase activity.
AB  - A comparative study of nerve regeneration was performed on vascularized nerve
      graft (VNG) and free nerve graft (FNG) in Fischer strain rats. A segment of the
      sciatic nerve with vascular pedicle of the femoral artery and vein was harvested
      from syngeneic donor rat for the VNG group and the sciatic nerve in the same
      length without vascular pedicle was harvested for the FNG group. They were
      transplanted to a nerve defect in the sciatic nerve of syngeneic recipient rats.
      At 2, 4, 6, 8, 12, 16, and 24 weeks after operation, the sciatic nerves were
      biopsied and processed for evaluation of choline acetyltransferase (CAT)
      activity, histological studies, and measurement of wet weight of the muscle
      innervated by the sciatic nerve. Electrophysiological evaluation of the grafted
      nerve was also performed before sacrifice. The average CAT activity in the distal
      to the distal suture site was 383 cpm in VNG and 361 cpm in FNG at 2 weeks; 6,189
      cpm in VNG and 2,264 cpm in FNG at 4 weeks; and 11,299 cpm in VNG and 9,424 cpm
      in FNG at 6 weeks postoperatively. The value of the VNG group was statistically
      higher than that of the FNG group at 4 weeks postoperatively.
      Electrophysiological and histological findings also suggested that nerve
      regeneration in the VNG group was superior to that in the FNG group during the
      same period. However, there was no significant difference between the two groups
      after 6 weeks postoperatively in any of the evaluations. The CAT measurement was
      useful in the experiments, because it was highly sensitive and reproducible.

PMID- 11288152
TI  - Delayed penile replantation after prolonged warm ischemia.
AB  - We report a case of microsurgical replantation of traumatic self-amputation of
      penis after prolonged warm ischemia as a result of delayed presentation. At 12
      weeks postoperative follow-up evaluation, the patient exhibited good urinary
      flow, spontaneous erection, and a normal response to pharmacological stimulation.

PMID- 11288153
TI  - Combined pancreaticoduodenal-kidney transplantation in rats.
AB  - The objective of this work was to establish a stable and simple simultaneous
      pancreaticoduodenal-kidney transplantation model in rats. The methods involved
      harvesting a pancreaticoduodenal-kidney (left) (PDK) and 1-cm inferior vena cava
      (IVC) with a 0.5-cm left and right iliac communis vein from donors and to "cuff"
      anastomose between portal vein and right iliac communis vein, left kidney vein,
      and left iliac communis vein, converging donor portal vein and left kidney vein
      into IVC together. Next, we performed an anastomosis of the donor arterial
      segment and recipient abdominal aorta and a "cuff" anastomosis between donor IVC
      and recipient left kidney vein. Of 67 transplanted rats in which diabetes was
      induced, 57 survived >7 days, 55 survived 1 month, 54 rats have survived >4
      months. In 51 rats, nonfasting plasma glucose levels were euglycemic. We
      performed three "cuff" anastomoses to simplify the surgical procedure and to
      shorten the ischemia time of the graft; the recipient vein system has an
      integrated endovenous membrane to avoid venous thrombi in venous anastomosis
      sites.

PMID- 11288154
TI  - Effects of liposome-mediated gene transfer of VEGF in ischemic rat gracilis
      muscle.
AB  - The purpose of the current study was to determine the effects of vascular
      endothelial growth factor (VEGF) on muscle flap survival and vascularity in a rat
      gracilis ischemia-reperfusion model. A total of 12 adult male Wistar rats were
      divided into two groups (n = 6). The experimental group received the plasmid
      encoding VEGF(165) cDNA plus lipofectamine (cationic liposome) injected directly
      to the gracilis muscle following 4 h of ischemia. The control group received
      lipofectamine only. The viability and vascularity of the flaps were evaluated
      after 7 days of reperfusion. The data demonstrated that the VEGF plasmid- and
      lipofectamine-treated muscle flaps had significantly greater total survival and
      capillary count 7 days after reperfusion compared with the flaps treated only
      with lipofectamine. These results indicate that VEGF exerts a protective effect
      on ischemic skeletal muscle flaps.

PMID- 11288155
TI  - Video microsurgery: early experience with an alternative operating magnification
      system.
AB  - Since Nylen first used an operating microscope in 1921, its basic design has
      remained fundamentally unchanged. Microsurgical procedures are still performed
      while viewing the subject through binocular eyepieces. This article examines the
      potential to perform microsurgery using video technology, operating with a
      television monitor. The development of the videomicroscope is discussed together
      with its early trials. The results show the potential to perform simple
      microsurgical procedures while viewing the procedure in a two-dimensional format.
      The advantages and disadvantages of such a system are discussed, together with
      future implications.

PMID- 11288156
TI  - Muscle free flaps with full-thickness skin grafting: Improved contour over
      traditional musculocutaneous free flaps.
AB  - Occasionally, the aesthetic contour of a musculocutaneous flap can be improved by
      using the skin paddle as a full-thickness skin graft to cover the free muscle
      flap. In three patients, traditional musculocutaneous free flap coverage of
      wounds would have resulted in excess soft tissue bulk. To optimize final contour,
      the subcutaneous tissue was excised, and the skin replaced as a full-thickness
      skin graft. Problems with postoperative flap monitoring and skin graft take were
      not encountered. This technique offers the microsurgeon a simple method to
      optimize the aesthetic results of composite free tissue transfer.

PMID- 11288157
TI  - The socioeconomic impact of Alzheimer's disease.

PMID- 11288158
TI  - A double blind, randomized clinical trial assessing the efficacy and safety of
      augmenting standard antidepressant therapy with nimodipine in the treatment of
      'vascular depression'.
AB  - BACKGROUND: 'Vascular depression' may be caused by cerebrovascular disease.
      Calcium channel blockers, which are putative treatments for cerebrovascular
      disease, might be expected to improve depression reduction and to prevent
      recurrence of depression in this patient population. This clinical trial was
      designed to test these hypotheses. DESIGN: This was a controlled, double blind,
      randomized clinical trial in which 84 patients with vascular depression
      (Alexopoulos criteria) were treated with antidepressants at standard doses.
      Patients were also randomized to nimodipine (n = 40) or an inactive comparator,
      vitamin C (n = 44). Treatment outcomes were assessed using the Hamilton
      depression rating scale (HDRS) regularly up to 300 days after treatment
      initiation. RESULTS: As expected, depression reduction was successful in most
      patients. In addition, those treated with nimodipine plus an antidepressant had
      greater improvements in depression overall in repeated measures ANCOVA (F(1,81) =
      8.64, p = 0.004). As well a greater proportion of nimodipine-treated participants
      (45 versus 25%) exhibited a full remission (HDRS < or = 10) (chi(2)(df, 1) =
      3.71, p = 0.054). Among those experiencing a substantial response in the first 60
      days (50% reduction in HDRS), fewer patients on nimodipine (7.4%) had a
      recurrence of major depression when compared to those on antidepressant alone
      (32%) (chi(2)(df, 1) = 3.59, p = 0.058). CONCLUSIONS: In treating vascular
      depression, augmentation of antidepressant therapy with a calcium-channel blocker
      leads to greater depression reduction and lower rates of recurrence. These
      findings support the argument that cerebrovascular disease is involved in the
      pathogenesis and recurrence of depression in these patients.

PMID- 11288159
TI  - The cognitive decline scale of the psychogeriatric assessment scales (PAS):
      longitudinal data on its validity.
AB  - OBJECTIVE: The Cognitive Decline scale of the Psychogeriatric Assessment Scales
      (PAS)1 uses informant data to assess retrospectively change from earlier in life.
      Data from a 7-8-year longitudinal study were used to assess the validity of this
      scale against changes in cognitive performance and mortality. DESIGN AND
      MEASURES: PAS data were collected on three occasions, with gaps of 3.6 and 4.1
      years between the waves. The Cognitive Decline score at Wave 3 was validated
      retrospectively against actual change on a brief test of current cognitive status
      (the PAS Cognitive Impairment scale) over the three waves, while the Cognitive
      Decline score at Wave 1 was assessed for predictive validity against future
      mortality and cognitive change. SETTING: A community survey in the Australian
      cities of Canberra and Queanbeyan. PARTICIPANTS: Participants were aged 70+ at
      the beginning of the study. The sample size varied from 729 to 279, depending on
      the number of waves involved. RESULTS: Participants with scores of 4+ on the
      Cognitive Decline scale at Wave 3 showed substantial deterioration over the
      previous 7-8 years. Scores of 4+ at Wave 1 predicted mortality and further
      cognitive deterioration. CONCLUSIONS: The Cognitive Decline scale allows a valid
      retrospective assessment of change and has predictive validity for subsequent
      cognitive deterioration and increased mortality.

PMID- 11288160
TI  - Care management and the care programme approach: towards integration in old age
      mental health services.
AB  - OBJECTIVE: To examine the relationship between care management arrangements and
      the Care Programme Approach (CPA) in the context of old age mental health
      services and, particularly, dementia services. METHOD: The information reported
      is from a national study of care management arrangements, funded by the
      Department of Health. A response rate of 77% was obtained from local authority
      social services departments. RESULTS: In old age mental health services over half
      of the respondents reported joint screening arrangements for health and social
      care, almost four-fifths reported both joint criteria for the allocation of key
      workers and a clear definition of monitoring responsibilities. Of the latter over
      two-fifths were reported as being the same in care management and the CPA. Forty
      six per cent of respondents provided a specialist service for people with
      dementia. Three-fifths of respondents reported that they did not apply CPA to
      people with dementia who were in receipt of care management or did so in less
      than 20% of cases. Where the CPA was applied it was more likely that a priority
      would be accorded to care management. A quarter of respondents reported the
      shared use of assessment documentation for people with dementia. DISCUSSION: The
      findings are set in the context of service developments to date and the
      implementation of the two systems of community based coordinated care for older
      people with mental health problems. Inter-authority variations are noted and the
      potential for greater service integration within the current legislative
      framework assessed.

PMID- 11288161
TI  - Institutionalization of demented elderly: the role of caregiver characteristics.
AB  - BACKGROUND: Three sets of caregiver characteristics were examined with respect to
      their explanatory value for institutionalization of demented elderly people:
      commitment to the caregiving relationship, psychological distress, and
      personality traits. METHOD: Logistic regression was used to test whether these
      caregiver characteristics were risk factors for institutionalization of demented
      elderly people in the first year after baseline measurement (N = 138). Control
      variables were caregivers' sex, age and education. RESULTS: The results showed
      the importance of commitment to the caregiving relationship, indicated by type of
      relationship between caregiver and care recipient. Demented people cared for by
      non-spouses were more likely to be institutionalized as compared to those cared
      for by spouses. For non-spouse care-givers, being more extravert increased the
      likelihood of institutional placement, whereas for spouse caregivers perceiving
      more pressure from informal increased this likelihood. CONCLUSIONS: These
      findings are in agreement with the assumption that non-spouses are less strongly
      committed to the caregiving relationship as compared to spouses. Results were
      independent from elders' impairment in cognitive functioning and (Instrumental)
      Activities of Daily Living. Caregivers' psychopathology was not a risk factor at
      all, which is a matter of concern, regarding the consequences for caregivers' own
      health and health-care utilization, but also for their treatment of the demented
      elder.

PMID- 11288162
TI  - Depression in late life, cognitive decline and white matter pathology in two
      clinico-pathologically investigated cases.
AB  - CASE REPORTS: We report two cases of late life depression who became
      progressively more resistant to treatment, developed cognitive impairment, and
      began to exhibit neurological abnormalities and evidence of vascular disease. A
      discussion of the clinical features of the cases is accompanied by reports of
      neuropathology and neuroimaging findings. Extensive white matter lesions were
      present on computed tomography in both patients, and basal ganglia infarcts were
      seen in one. Neuropathology revealed evidence of cerebral atrophy, demyelination
      and white matter lesions in addition to cerebrovascular and generalised vascular
      disease. Neither patient exhibited Alzheimer pathology outwith the norm for their
      age. We believe this to be the first report of neuropathological findings in
      depression with white matter changes. LITERATURE REVIEW: The pathological basis
      of white matter lesions and their relationship to depression, its age of onset
      and clinical features is addressed in relation to the cases described.
      Pathological investigation of white matter lesions has not previously been
      carried out in depression and hypotheses regarding their nature in this illness
      are based on extrapolation from research in a variety of other disorders. The
      association of depression with vascular risk factors is considered, as is the
      relationship between depression and cognitive deficits. There is a need for
      further investigation in this area.

PMID- 11288163
TI  - Psychometric evaluation of a short observational tool for small-scale research
      projects in dementia.
AB  - Dementia is a degenerating illness and the lack of a reliable measure of self
      report in particular presents particular difficulties for research. Often in the
      later stages of dementia behavioural measurement is the only tool available for
      the evaluation of treatment techniques. This paper describes and evaluates a
      short observational tool suitable for clinical assessment purposes. The scale has
      been shown to have the potential for adequate inter-rater reliability, test
      retest reliability, and convergent and divergent validity, if the study
      limitations reflecting statistical rather than ecological validity, and
      limitations of sample size are borne in mind.

PMID- 11288164
TI  - The prevalence and outcome of depression and dementia in Botany's elderly
      population.
AB  - BACKGROUND: Large epidemiological studies of adult populations have reported
      depression to be less prevalent in old age than among younger adults, whereas
      studies limited to older persons have reported rates that vary considerably, some
      showing high rates of depression. There was, therefore, reason to check data from
      a study that reported high rates, and to review evidence in relation to diagnosis
      and outcome. METHOD: Re-examination of data from a 1985 survey of elderly people
      living at home (n = 146). Depression and cognitive impairment were also assessed
      in a local hostel (n = 42) and nursing home (n = 74). DSM diagnoses were made by
      an old age psychiatrist. In the nursing home, 23 other residents could not
      respond to interview questions but were considered to have severe dementia.
      Subjects in all three settings were followed up after 4 years. RESULTS: Seven
      community subjects (4.5%; confidence interval 1.3-8.3%) and three in residential
      care fulfilled criteria for major depression. The estimated total prevalence of
      depressive disorders among elderly in Botany was between 13.0 and 13.6% (4.6%
      major depression, 3.6% dementia with depression, 5.4% other depressive
      disorders). In 1985, the prevalence of dementia among those living at home was
      11%. Four-year mortality in the dementia cases was 60%. CONCLUSIONS: Botany has a
      high prevalence of dementia and depression among elderly people. The recent cross
      age. Australian study of mental health and well-being provided an inaccurate
      report concerning the pattern of mental disorders in old age.

PMID- 11288165
TI  - Attempted and completed suicide in older subjects: results from the WHO/EURO
      Multicentre Study of Suicidal Behaviour.
AB  - OBJECTIVE: The authors present an analysis of findings for the 65 years and over
      age group from the WHO/EURO Multicentre Study of Suicidal Behaviour (1989-93).
      METHODS: Multinational data on non-fatal suicidal behaviour is derived from 1518
      subjects in 16 European centres. Local district data on suicide were available
      from 10 of the collaborating centres. RESULTS: Stockholm (Sweden), Pontoise
      (France) and Oxford (UK) had the highest suicide attempts rates. In most centres,
      the majority of elderly who attempted suicide were widow(er)s, often living
      alone, who used predominantly voluntary drug ingestion. Non-fatal suicidal
      behaviour decreased with increasing age, whereas suicide rates rose. The ratio
      between fatal and non-fatal behaviours was 1:2, that for males/females almost
      1:1. In the years considered, substantial stability in suicide and attempted
      suicide rates was observed. As their age increased, suicidal subjects displayed
      only a limited tendency to repeat self-destructive acts. Moreover, there was
      little correlation between attempted suicide and suicide rates, which carries
      different clinical implications for non-fatal suicidal behaviour in the elderly
      compared with younger subjects in the same WHO/EURO study.

PMID- 11288166
TI  - Dementia with Lewy bodies in Down's syndrome.
AB  - The association between Down's syndrome (DS) and Alzheimer's disease is well
      established. This paper presents a review of the literature, suggesting a
      possible association between DS and the more recently recognised dementia with
      Lewy bodies (DLB). Patients with DLB frequently present with changes in affect
      and behaviour, and in particular with psychotic symptoms. The literature suggests
      a possible role for atypical neuroleptics in the management of psychosis in DLB.

PMID- 11288167
TI  - The effectiveness of very short scales for depression screening in elderly
      medical patients.
AB  - OBJECTIVE: To compare very short scales for screening for depression with longer,
      widely used scales. METHODS: Eighty-seven patients over the age of 60 who were
      admitted to rehabilitation wards or were attending a day rehabilitation facility
      at a British teaching hospital were screened for depression using the 1-item
      mental health inventory, and the 4-item, 15-item and 30-item geriatric depression
      scales. The sensitivity, specificity, and areas under receiver operating
      characteristic curves were compared, with the diagnostic criteria for research of
      ICD-10 providing the criterion diagnosis of depressive episode. RESULTS: All the
      scales had comparable sensitivity (82.4-100%), specificity (60.0-71.4%), and
      positive predictive values (33.3-42.9%). Comparison of receiver operating
      characteristic curves for each scale showed no statistically significant
      difference between them (range 0.80-0.88). CONCLUSIONS: The very short scales
      performed just as well as the widely used longer screening scales in this
      population. They are worthy of further examination in elderly populations at risk
      of depression, and may be particularly suitable for older adults due to their
      brevity and ease of use.

PMID- 11288168
TI  - Equity of access to a memory clinic in Melbourne? Non-English speaking background
      attenders are more severely demented and have increased rates of psychiatric
      disorders.
AB  - OBJECTIVES: The aim of this study was to compare demographic and clinical
      features of patients from Non-English Speaking Background (NESB) with those from
      English Speaking Background (ESB) who attended a memory clinic in Melbourne,
      Australia. METHODS: Data on 556 consecutive patients attending the memory clinic
      were analysed retrospectively. All patients were assessed by a geriatrician
      (Italian speaking) or psychogeriatrician with the aid of Cambridge Examination
      for Mental Disorders in the Elderly (CAMDEX) interview schedule. Patients were
      classified into the categories of dementia, functional psychiatric disorder
      (including depression), cognitive impairment other than dementia and normal,
      using ICD 10 criteria. Severity of dementia was determined using the Clinical
      Dementia Rating scale. Demographic information and use of community services were
      also documented. RESULTS: Of those seen, 148 (28.8%) were of NESB, the majority
      Italian (69, 12.4%). Patients of NESB were younger (p = 0.001), less educated (p
      = 0.001) and less likely to live alone (p = 0.009) compared to persons of ESB.
      Those of NESB were more likely present with a functional psychiatric disorder
      (particularly depression) or normal cognition (p = 0.001). Patients of NESB with
      dementia presented at a later stage of their disease as determined by CDR (p =
      0.003). Those of NESB scored significantly lower (more impaired) on CAMCOG in all
      patients seen (including normal and psychiatric groups) (p = 0.02). CONCLUSIONS:
      The clinical and demographic features of people of NESB referred to a memory
      clinic in Melbourne, Australia, differ from their ESB counterparts, with specific
      groups being under represented. This has implications for equity of assessment,
      service provision and utilisation for those of ethnically diverse backgrounds.

PMID- 11288170
TI  - The management of demented people with feeding problem.

PMID- 11288171
TI  - Anticholinesterase drugs for alcoholic Korsakoff syndrome.

PMID- 11288172
TI  - Current awareness in geriatric psychiatry.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley & Sons are providing a current awareness service in each issue
      of the journal. The bibliography contains newly published material in the field
      of geriatric psychiatry. Each bibliography is divided into 9 sections: 1 Books,
      Reviews & Symposia; 2 General; 3 Assessment; 4 Epidemiology; 5 Therapy; 6 Care; 7
      Dementia; 8 Depression; 9 Psychology. Within each section, articles are listed in
      alphabetical order with respect to author. If, in the preceding period, no
      publications are located relevant to any one of these headings, that section will
      be omitted

PMID- 11288174
TI  - Prediction of protein cellular attributes using pseudo-amino acid composition.
AB  - The cellular attributes of a protein, such as which compartment of a cell it
      belongs to and how it is associated with the lipid bilayer of an organelle, are
      closely correlated with its biological functions. The success of human genome
      project and the rapid increase in the number of protein sequences entering into
      data bank have stimulated a challenging frontier: How to develop a fast and
      accurate method to predict the cellular attributes of a protein based on its
      amino acid sequence? The existing algorithms for predicting these attributes were
      all based on the amino acid composition in which no sequence order effect was
      taken into account. To improve the prediction quality, it is necessary to
      incorporate such an effect. However, the number of possible patterns for protein
      sequences is extremely large, which has posed a formidable difficulty for
      realizing this goal. To deal with such a difficulty, the pseudo-amino acid
      composition is introduced. It is a combination of a set of discrete sequence
      correlation factors and the 20 components of the conventional amino acid
      composition. A remarkable improvement in prediction quality has been observed by
      using the pseudo-amino acid composition. The success rates of prediction thus
      obtained are so far the highest for the same classification schemes and same data
      sets. It has not escaped from our notice that the concept of pseudo-amino acid
      composition as well as its mathematical framework and biochemical implication may
      also have a notable impact on improving the prediction quality of other protein
      features.

PMID- 11288173
TI  - Automated multiple structure alignment and detection of a common substructural
      motif.
AB  - While a number of approaches have been geared toward multiple sequence
      alignments, to date there have been very few approaches to multiple structure
      alignment and detection of a recurring substructural motif. Among these, none
      performs both multiple structure comparison and motif detection simultaneously.
      Further, none considers all structures at the same time, rather than initiating
      from pairwise molecular comparisons. We present such a multiple structural
      alignment algorithm. Given an ensemble of protein structures, the algorithm
      automatically finds the largest common substructure (core) of C(alpha) atoms that
      appears in all the molecules in the ensemble. The detection of the core and the
      structural alignment are done simultaneously. Additional structural alignments
      also are obtained and are ranked by the sizes of the substructural motifs, which
      are present in the entire ensemble. The method is based on the geometric hashing
      paradigm. As in our previous structural comparison algorithms, it compares the
      structures in an amino acid sequence order-independent way, and hence the
      resulting alignment is unaffected by insertions, deletions and protein chain
      directionality. As such, it can be applied to protein surfaces, protein-protein
      interfaces and protein cores to find the optimally, and suboptimally spatially
      recurring substructural motifs. There is no predefinition of the motif. We
      describe the algorithm, demonstrating its efficiency. In particular, we present a
      range of results for several protein ensembles, with different folds and
      belonging to the same, or to different, families. Since the algorithm treats
      molecules as collections of points in three-dimensional space, it can also be
      applied to other molecules, such as RNA, or drugs.

PMID- 11288175
TI  - Multiple linear regression for protein secondary structure prediction.
AB  - In the present work, a novel method was proposed for prediction of secondary
      structure. Over a database of 396 proteins (CB396) with a three-state-defining
      secondary structure, this method with jackknife procedure achieved an accuracy of
      68.8% and SOV score of 71.4% using single sequence and an accuracy of 73.7% and
      SOV score of 77.3% using multiple sequence alignments. Combination of this method
      with DSC, PHD, PREDATOR, and NNSSP gives Q3 = 76.2% and SOV = 79.8%.

PMID- 11288176
TI  - Crystal structures of the peanut lectin-lactose complex at acidic pH: retention
      of unusual quaternary structure, empty and carbohydrate bound combining sites,
      molecular mimicry and crystal packing directed by interactions at the combining
      site.
AB  - The crystal structures of a monoclinic and a triclinic form of the peanut lectin
      lactose complex, grown at pH 4.6, have been determined. They contain two and one
      crystallographically independent tetramers, respectively. The unusual "open"
      quaternary structure of the lectin, observed in the orthorhombic complex grown in
      neutral pH, is retained at the acidic pH. The sugar molecule is bound to three of
      the eight subunits in the monoclinic crystals, whereas the combining sites in
      four are empty. The lectin-sugar interactions are almost the same at neutral and
      acidic pH. A comparison of the sugar-bound and free subunits indicates that the
      geometry of the combining site is relatively unaffected by ligand binding. The
      combining site of the eighth subunit in the monoclinic crystals is bound to a
      peptide stretch in a loop from a neighboring molecule. The same interaction
      exists in two subunits of the triclinic crystals, whereas density corresponding
      to sugar exists in the combining sites of the other two subunits. Solution
      studies show that oligopeptides with sequences corresponding to that in the loop
      bind to the lectin at acidic pH, but only with reduced affinity at neutral pH.
      The reverse is the case with the binding of lactose to the lectin. A comparison
      of the neutral and acidic pH crystal structures indicates that the molecular
      packing in the latter is directed to a substantial extent by the increased
      affinity of the peptide loop to the combining site at acidic pH.

PMID- 11288178
TI  - Population analyses of kinetic partitioning in protein folding.
AB  - A simple lattice model of protein folding is studied in order to analyze the
      kinetic partitioning phenomena in the energy landscape perspective. By
      restricting the area of conformational space, it becomes possible to follow many
      Monte Carlo trajectories until they reach equilibrium. Alteration of population
      of trajectories is monitored and the relations between the energy landscape and
      kinetics are examined. Kinetic partitioning phenomena are categorized into
      different types in terms of characteristic time constants and partitioning ratio.
      In a specific partitioning process, refolding proceeds along the parallel
      pathways; the time constants have a temperature dependence similar to that
      observed in hen lysozyme. High-energy conformations are classified into groups
      according to the probability that the trajectories starting from those
      conformations will reach each energy valley. The partitioning ratio is determined
      by the way in which the conformational space is organized into these groups.

PMID- 11288177
TI  - Analysis of a data set of paired uncomplexed protein structures: new metrics for
      side-chain flexibility and model evaluation.
AB  - We compiled and analyzed a data set of paired protein structures containing
      proteins for which multiple high-quality uncomplexed atomic structures were
      available in the Protein Data Bank. Side-chain flexibility was quantified,
      yielding a set of residue- and environment-specific confidence levels describing
      the range of motion around chi1 and chi2 angles. As expected, buried residues
      were inflexible, adopting similar conformations in different crystal structure
      analyses. Ile, Thr, Asn, Asp, and the large aromatics also showed limited
      flexibility when exposed on the protein surface, whereas exposed Ser, Lys, Arg,
      Met, Gln, and Glu residues were very flexible. This information is different from
      and complementary to the information available from rotamer surveys. The
      confidence levels are useful for assessing the significance of observed side
      chain motion and estimating the extent of side-chain motion in protein structure
      prediction. We compare the performance of a simple 40 degrees threshold with
      these quantitative confidence levels in a critical evaluation of side-chain
      prediction with the program SCWRL.

PMID- 11288180
TI  - Optimization of solvation models for predicting the structure of surface loops in
      proteins.
AB  - A novel procedure for optimizing the atomic solvation parameters (ASPs) sigma(i)
      developed recently for cyclic peptides is extended to surface loops in proteins.
      The loop is free to move, whereas the protein template is held fixed in its X-ray
      structure. The energy is E(tot) = E(FF)(epsilon = nr) + summation operator
      sigma(i)A(i), where E(FF)(epsilon = nr) is the force-field energy of the loop
      loop and loop-template interactions, epsilon = nr is a distance-dependent
      dielectric constant, and n is an additional parameter to be optimized. A(i) is
      the solvent-accessible surface area of atom i. The optimal sigma(i) and n are
      those for which the loop structure with the global minimum of E(tot)(n, sigma(i))
      becomes the experimental X-ray structure. Thus, the ASPs depend on the force
      field and are optimized in the protein environment, unlike commonly used ASPs
      such as those of Wesson and Eisenberg (Protein Sci 1992;1:227-235). The latter
      are based on the free energy of transfer of small molecules from the gas phase to
      water and have been traditionally combined with various force fields without
      further calibration. We found that for loops the all-atom AMBER force field
      performed better than OPLS and CHARMM22. Two sets of ASPs [based on AMBER (n =
      2)], optimized independently for loops 64-71 and 89-97 of ribonuclease A, were
      similar and thus enabled the definition of a best-fit set. All these ASPs were
      negative (hydrophilic), including those for carbon. Very good (i.e., small) root
      mean-square-deviation values from the X-ray loop structure were obtained with the
      three sets of ASPs, suggesting that the best-fit set would be transferable to
      loops in other proteins as well. The structure of loop 13-24 is relatively
      stretched and was insensitive to the effect of the ASPs.

PMID- 11288179
TI  - Folding of intracellular retinol and retinoic acid binding proteins.
AB  - The folding mechanisms of cellular retinol binding protein II (CRBP II), cellular
      retinoic acid binding protein I (CRABP I), and cellular retinoic acid binding
      protein II (CRABP II) were examined. These beta-sheet proteins have very similar
      structures and higher sequence homologies than most proteins in this diverse
      family. They have similar stabilities and show completely reversible folding at
      equilibrium with urea as a denaturant. The unfolding kinetics of these proteins
      were monitored during folding and unfolding by circular dichroism (CD) and
      fluorescence. During unfolding, CRABP II showed no intermediates, CRABP I had an
      intermediate with nativelike secondary structure, and CRBP II had an intermediate
      that lacked secondary structure. The refolding kinetics of these proteins were
      more similar. Each protein showed a burst-phase change in intensity by both CD
      and fluorescence, followed by a single observed phase by both CD and fluorescence
      and one or two additional refolding phases by fluorescence. The fluorescence
      spectral properties of the intermediate states were similar and suggested a
      gradual increase in the amount of native tertiary structure present for each step
      in a sequential path. However, the rates of folding differed by as much as 3
      orders of magnitude and were slower than those expected from the contact order
      and topology of these proteins. As such, proteins with the same final structure
      may not follow the same route to the native state.

PMID- 11288181
TI  - Replacement of thrombin residue G184 with Lys or Arg fails to mimic Na+ binding.
AB  - Na+ binding to thrombin enhances the catalytic activity toward numerous synthetic
      and natural substrates. The bound Na+ is located in a solvent channel 16 A away
      from the catalytic triad, and connects with D189 in the S1 site through an
      intervening water molecule. Molecular modeling indicates that the G184K
      substitution in thrombin positions the protonated epsilon-amino group of the Lys
      side-chain to replace the bound Na+. Likewise, the G184R substitution positions
      the guanidinium group of the longer Arg side-chain to replace both the bound Na+
      and the connecting water molecule to D189. We explored whether the G184K or G184R
      substitution would replace the bound Na+ and yield a thrombin derivative
      stabilized in the highly active fast form. Both the G184K and G184R mutants lost
      sensitivity to monovalent cations, as expected, but their activity toward a
      chromogenic substrate was compromised up to 200-fold as a result of impaired
      diffusion into the S1 site and decreased deacylation rate. Interestingly, both
      G184K and G184R substitutions compromised cleavage of procoagulant substrates
      fibrinogen and PAR1 more than that of the anticoagulant substrate protein C.
      These findings demonstrate that Na+ binding to thrombin is difficult to mimic
      functionally with residue side-chains, in analogy with results from other
      systems.

PMID- 11288182
TI  - 2.8-A crystal structure of a nontoxic type-II ribosome-inactivating protein,
      ebulin l.
AB  - Ebulin l is a type-II ribosome-inactivating protein (RIP) isolated from the
      leaves of Sambucus ebulus L. As with other type-II RIP, ebulin is a disulfide
      linked heterodimer composed of a toxic A chain and a galactoside-specific lectin
      B chain. A normal level of ribosome-inactivating N-glycosidase activity,
      characteristic of the A chain of type-II RIP, has been demonstrated for ebulin l.
      However, ebulin is considered a nontoxic type-II RIP due to a reduced
      cytotoxicity on whole cells and animals as compared with other toxic type-II RIP
      like ricin. The molecular cloning, amino acid sequence, and the crystal structure
      of ebulin l are presented and compared with ricin. Ebulin l is shown to bind an A
      chain substrate analogue, pteroic acid, in the same manner as ricin. The
      galactoside-binding ability of ebulin l is demonstrated crystallographically with
      a complex of the B chain with galactose and with lactose. The negligible
      cytotoxicity of ebulin l is apparently due to a reduced affinity for
      galactosides. An altered mode of galactoside binding in the 2gamma subdomain of
      the lectin B chain primarily causes the reduced affinity.

PMID- 11288183
TI  - Enzymatic circularization of a malto-octaose linear chain studied by stochastic
      reaction path calculations on cyclodextrin glycosyltransferase.
AB  - Cyclodextrin glycosyltransferase (CGTase) is an enzyme belonging to the alpha
      amylase family that forms cyclodextrins (circularly linked oligosaccharides) from
      starch. X-ray work has indicated that this cyclization reaction of CGTase
      involves a 23-A movement of the nonreducing end of a linear malto-oligosaccharide
      from a remote binding position into the enzyme acceptor site. We have studied the
      dynamics of this sugar chain circularization through reaction path calculations.
      We used the new method of the stochastic path, which is based on path integral
      theory, to compute an approximate molecular dynamics trajectory of the large (75
      kDa) CGTase from Bacillus circulans strain 251 on a millisecond time scale. The
      result was checked for consistency with site-directed mutagenesis data. The
      combined data show how aromatic residues and a hydrophobic cavity at the surface
      of CGTase actively catalyze the sugar chain movement. Therefore, by using
      approximate trajectories, reaction path calculations can give a unique insight
      into the dynamics of complex enzyme reactions.

PMID- 11288184
TI  - Is it a paradox or misinterpretation?
AB  - The paradox recently raised by Wang and Yuan (Proteins 2000;38:165-175) in
      protein structural class prediction is actually a misinterpretation of the data
      reported in the literature. The Bayes decision rule, which was deemed by Wang and
      Yuan to be the most powerful method for predicting protein structural classes
      based on the amino acid composition, and applied by these investigators to derive
      the upper limit of prediction rate for structural classes, is actually completely
      the same as the component-coupled algorithm proposed by previous investigators
      (Chou et al., Proteins 1998;31:97-103). Owing to lack of a complete or near
      complete training data set, the upper limit rate thus derived by these
      investigators might be both invalid and misleading. Clarification of these points
      will further stimulate investigation of this interesting area.

PMID- 11288185
TI  - The prediction accuracy for protein structural class by the component-coupled
      method is around 60%.

PMID- 11288186
TI  - Equity considerations in health care: the relevance of claims.
AB  - The general issues of equity and efficiency are central to the analysis of
      resource allocation problems in health care. We examine them using axiomatic
      bargaining theory. We study different solutions that have been proposed and
      relate them to previous literature on health care allocation. In particular, we
      focus on the solutions based on axiomatic bargaining with claims, and show that
      they are appealing as distributive criteria in health policy. Finally, we present
      the results of a survey that tries to elicit moral intuitions of people about
      resource allocation problems and their different solutions.

PMID- 11288187
TI  - Targeted health insurance in a low income country and its impact on access and
      equity in access: Egypt's school health insurance.
AB  - Governments are constantly faced with competing demands for public funds, thereby
      necessitating careful use of scarce resources. In Egypt, the School Health
      Insurance Programme (SHIP) is a government subsidized health insurance system
      that targets school children. The primary goals of the SHIP include improving
      access and equity in access to health care for children while, at the same time,
      ensuring programme sustainability. Using the Egyptian Household Health
      Utilization and Expenditure Survey (1995), this paper empirically assesses the
      extent to which the SHIP achieves its stated goals. Our findings show that the
      SHIP significantly improved access by increasing visit rates and reducing
      financial burden of use (out-of-pocket expenditures). With regard to the success
      of targeting the poor, conditional upon being covered, the SHIP reduced the
      differentials in visit rates between the highest and lowest income children.
      However, only the middle-income children benefitted from reduced financial burden
      (within group equity). Moreover, by targeting the children through school
      enrollment, the SHIP increased the differentials in the average level of access
      between school-going children and those not attending school (overall equity).
      Children not attending school tend to be poor and living in rural areas. Our
      results also indicate that original calculations may underestimate the SHIP
      financial outlays, thereby threatening the long run financial sustainability of
      the programme.

PMID- 11288188
TI  - Demand for traditional medicine in Taiwan: a mixed Gaussian-Poisson model
      approach.
AB  - Hurdle count models are used to examine the participation and consumption
      decisions in Chinese medicine use. Motivated by a household production model, a
      second censoring mechanism is introduced into existing single-hurdle models, and
      the resulting specification accommodates conscientious abstainers, as well as
      economic non-consumers, and admits excessive zeros in the sample. In contrast to
      previous studies that found few predictors, empirical results based on a
      Taiwanese national sample suggest that Western medicine is a gross substitute to
      Chinese medicine, and both time price and money price play more important roles
      than income. Insurance, lifestyle and demographics also determine the use of
      Chinese medicine.

PMID- 11288189
TI  - On the societal value of health care: what do we know about the person trade-off
      technique?
AB  - The person trade-off (PTO) technique has been suggested as a means of eliciting
      social preferences for health care, both the valuation of health care
      interventions and, more recently, to inform on the weights that society may
      attach to other decision-making criteria (e.g. the severity of a patients pre
      treatment condition). Given the increased attention afforded to the PTO
      technique, this review examines the current evidence to inform on the ability of
      the PTO to provide a measure of social preference. Applying criteria of
      practicality, reliability and validity to empirical and theoretical contributions
      to the PTO literature, the review finds that the technique has limited empirical
      support. Applications of the PTO have been in a largely experimental setting, the
      reliability of the PTO is unproven and the empirical validity of the technique,
      in terms its ability to reflect actual preferences, remains unclear. In the
      broader context of the valuation of health states or outcomes, all techniques are
      open to criticism. Given this position, the review finds support for the
      potential of the PTO in the assessment of the societal value of health care, and
      it supports further empirical inquiry on the PTO.

PMID- 11288190
TI  - The impact of including future medical care costs when estimating the costs
      attributable to a disease: a colorectal cancer case study.
AB  - A source of controversy in the economic literature concerns whether to include or
      exclude future medical care costs when computing attributable costs for
      lifesaving interventions. Although it is hypothesized that including future
      medical care costs will offset the cost savings achieved through prevention, the
      magnitude of the effect is not known. The objectives of the present study are to
      develop a methodology for estimating the excess costs of care among colorectal
      cancer patients, including and excluding future costs of care, and comparing
      these results with previous studies that do not include costs in added years of
      life. Subjects in the study included those identified with colorectal cancer
      drawn from the Surveillance, Epidemiology and End Results (SEER)-Medicare
      database and an age- and gender-matched control group drawn from the general
      Medicare population. Using the Kaplan-Meier Sample Average estimator, we directly
      estimate expected 11-year costs, and then, with the addition of some simple
      extrapolating assumptions, determine expected 25-year costs. The latter time
      horizon captures lifetime costs for over 90% of the cohort. Males results for
      discounted, stage-specific 11- versus 25-year excess costs: in situ, 22411
      dollars versus 23494 dollars; Stage 1, 29365 dollars versus 32510 dollars; Stage
      2, 28114 dollars versus 25263 dollars; Stage 3, 27397 dollars versus 19647
      dollars; Stage 4, 3006 dollars versus 7837 dollars. Trends were similar for
      females. It can be concluded that adding costs of care in future years for those
      whose colorectal cancer is prevented owing to screening greatly alters the
      estimate of lifetime excess costs for colorectal cancer patients, and can produce
      negative results for advanced stage disease. The results emphasize the need to
      adopt a standard approach for dealing with future costs when evaluating
      lifesaving interventions for cost-effectiveness analyses.

PMID- 11288191
TI  - Alcohol abuse and economic conditions: evidence from repeated cross-sections of
      individual-level data.
AB  - This study presents novel evidence on the relationship between macroeconomic
      conditions and patterns of alcohol consumption. Prior research has suggested that
      alcohol abuse varies procyclically, implying that income effects dominate any
      drinking patterns related to the opportunity cost of time or the psychological
      stress of recessions. However, those inferences have been based either on
      aggregate measures of consumption volume or possibly confounded cross-sectional
      identification strategies. This study examines these issues by evaluating
      detailed consumption data from the more than 700 000 respondents who participated
      in the Center for Disease Control and Prevention's Behavioral Risk Factor
      Surveillance System (BRFSS) surveys over the 1984-1995 period. The results
      provide robust evidence that the prevalence of binge drinking is strongly
      countercyclical. Furthermore, even among those who remain employed, binge
      drinking increased substantially during economic downturns. This combination of
      results suggests that recession-induced increases in the prevalence of binge
      drinking do not simply reflect an increased availability of leisure and may
      instead reflect the influence of economic stress.

PMID- 11288192
TI  - Reconsideration of discharge data to measure competition in the hospital
      industry.
AB  - Economists have long used state-collected discharge data to construct Hirschman
      Herfindahl (HH) indices measuring hospital competition. Since data are collected
      to determine the facility providing the service rather than ownership, the
      difference between the number of reporting facilities and the number of
      competitors has grown over time due to mergers and networking activities.
      Consequently, the validity of the discharge HH methodology, as currently
      employed, is in doubt. Comparing the annual census of New York state acute-care
      hospitals by the State and the American Hospital Association (AHA), we find that
      it is increasingly important to account for changes in ownership when
      constructing such indices.

PMID- 11288193
TI  - International Mass Spectrometry Society (IMSS).
AB  - This paper gives a brief description of the recently formalized International
      Mass Spectrometry Society (IMSS). It is presented here in order to increase
      awareness of the opportunities for collaboration in mass spectrometry in an
      international context. It also describes the recent 15th International Mass
      Spectrometry Conference, held August/September 2000, in Barcelona. Each of the
      authors is associated with the IMSS. The 15th Conference, which covers all of
      mass spectrometry on a triennial basis, was chaired by Professor Emilio Gelpi of
      the Instituto de Investigaciones Biomedicas, Barcelona. The outgoing and founding
      President of the IMSS is Professor Graham Cooks, Purdue University, and the
      incoming President is Professor Nico Nibbering, University of Amsterdam. Similar
      material has been provided to the Editors of other journals that cover mass
      spectrometry.

PMID- 11288194
TI  - Negative and positive ion matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry and positive ion nano-electrospray ionization quadrupole
      ion trap mass spectrometry of peptidoglycan fragments isolated from various
      Bacillus species.
AB  - A general approach for the detailed characterization of sodium borohydride
      reduced peptidoglycan fragments (syn. muropeptides), produced by muramidase
      digestion of the purified sacculus isolated from Bacillus subtilis (vegetative
      cell form of the wild type and a dacA mutant) and Bacillus megaterium (endospore
      form), is outlined based on UV matrix-assisted laser desorption/ionization time
      of-flight (MALDI-TOF) and nano-electrospray ionization (nESI) quadrupole ion trap
      (QIT) mass spectrometry (MS). After enzymatic digestion and reduction of the
      resulting muropeptides, the complex glycopeptide mixture was separated and
      fractionated by reversed-phase high-performance liquid chromatography. Prior to
      mass spectrometric analysis, the muropeptide samples were subjected to a
      desalting step and an aliquot was taken for amino acid analysis. Initial
      molecular mass determination of these peptidoglycan fragments (ranging from
      monomeric to tetrameric muropeptides) was performed by positive and negative ion
      MALDI-MS using the thin-layer technique with the matrix alpha-cyano-4
      hydroxycinnamic acid. The results demonstrated that for the fast molecular mass
      determination of large sample numbers in the 0.8-10 pmol range and with a mass
      accuracy of +/-0.07%, negative ion MALDI-MS in the linear TOF mode is the method
      of choice. After this kind of muropeptide screening often a detailed primary
      structural analysis is required owing to ambiguous data. Structural data could be
      obtained from peptidoglycan monomers by post-source decay (PSD) fragment ion
      analysis, but not from dimers or higher oligomers and not with the necessary
      sensitivity. Multistage collision-induced dissociation (CID) experiments
      performed on an nESI-QIT instrument were found to be the superior method for
      structural characterization of not only monomeric but also of dimeric and
      trimeric muropeptides. Up to MS4 experiments were sometimes necessary to obtain
      unambiguous structural information. Three examples are presented: (a) CID MSn (n
      = 2-4) of a peptidoglycan monomer (disaccharide-tripeptide) isolated from B.
      subtilis (wild type, vegetative cell form), (b) CID MSn (n = 2-4) of a
      peptidoglycan dimer (bis-disaccharide-tetrapentapeptide) obtained from a B.
      subtilis mutant (vegetative cell form) and (c) CID MS2 of a peptidoglycan trimer
      (a linear hexasaccharide with two peptide side chains) isolated from the spore
      cortex of B. megaterium. All MS(n) experiments were performed on singly charged
      precursor ions and the MS2 spectra were dominated by fragments derived from
      interglycosidic bond cleavages. MS3 and MS4 spectra exhibited mainly peptide
      moiety fragment ions. In case of the bis-disaccharide-tetrapentapeptide, the
      peptide branching point could be determined based on MS3 and MS4 spectra. The
      results demonstrate the utility of nESI-QIT-MS towards the facile determination
      of the glycan sequence, the peptide linkage and the peptide sequence and
      branching of purified muropeptides (monomeric up to trimeric forms). The wealth
      of structural information generated by nESI-QIT-MSn is unsurpassed by any other
      individual technique.

PMID- 11288195
TI  - Electrospray and matrix-assisted laser desorption/ionization mass spectral
      characterization of linear single nylon-6 oligomers.
AB  - Synthetic nylon-6 single molecular mass oligomers were studied by matrix-assisted
      laser desorption/ionization (MALDI) and electrospray ionization (ESI) mass
      spectrometry. These oligomers, considered as model compounds for the study of
      nylon-6 polymers, gave good mass spectrometric results using both MALDI and ESI.
      In spite of the gentle nature of both techniques, the MALDI and ESI spectra
      showed evidence of end-group cleavage from the oligomer chains. MALDI-MS was
      found to give similar fragmentation patterns for all of the oligomer samples. An
      increase in doubly charged ion signals with increasing oligomer mass was observed
      in the ESI mass spectra, as was end-group fragmentation. Signals from oligomer
      clusters were observed in ESI-MS for the dimer, tetramer and hexamer, most likely
      due to non-covalent bonding among the low-mass oligomer molecules.

PMID- 11288197
TI  - Operating principle of an electron monochromator in an axial magnetic field.
AB  - Electron monochromators which are operated within an axial magnetic (guiding)
      field are especially suitable for the production of monochromatic electrons at
      low energies. Although in principle the technology of such devices has an
      appreciable historic background, we have discovered experimentally important new
      features, which cannot be understood using the previously published theories of
      operation. An in-depth study of the electron trajectories in a crossed electric
      and magnetic field using Simion1 showed a number of possible pitfalls, which have
      to be avoided in construction and operation. From our simulations we derived a
      novel design and operational method, which is currently under evaluation. We have
      already demonstrated that using this novel design an electron energy resolution
      of about 50 meV is realistic.

PMID- 11288196
TI  - The metabolism of norethandrolone in the horse: characterization of 16-, 20- and
      21-oxygenated metabolites by gas chromatography/mass spectrometry.
AB  - After oral administration to a thoroughbred gelding, the anabolic steroid
      norethandrolone was converted into a complex mixture of oxygenated metabolites.
      These metabolites were extracted from the urine, deconjugated by methanolysis and
      converted to their O-methyloxime trimethylsilyl derivatives. Gas
      chromatographic/mass spectrometric analysis indicated the major metabolites to be
      19-norpregnane-3,16,17-triols, 19-norpregnane-3,17,20-triols and 3,17-dihydroxy
      19-norpregnan-21-oic acids. Some minor metabolites were also detected.

PMID- 11288198
TI  - Mass spectrometry of steroid glucuronide conjugates. I. Electron impact
      fragmentation of 5alpha-/5beta-androstan-3alpha-ol-17-one glucuronides, 5alpha
      estran-3alpha-ol-17-one glucuronide and deuterium-labelled analogues.
AB  - Owing to the developments of analytical instruments and interfaces (e.g. coupling
      high-performance liquid chromatography to mass spectrometry), there has been
      increased interest in new reference materials, for example in doping analysis
      with steroid glucuronide conjugates. The synthesized reference material has to
      pass several characterization steps including the use of gas chromatography/mass
      spectrometry (GC/MS) for its structure confirmation. In the present study, the
      fragmentation and mass spectrometric behaviour of several steroid glucuronide
      conjugates of endogenous and anabolic steroids after derivatization to
      pertrimethylsilylated products and to methyl ester pertrimethylsilylated products
      were investigated using GC/MS ion trap and GC/MS quadrupole instruments. The mass
      spectra of the derivatives of androsterone glucuronide, d5-androsterone
      glucuronide, epiandrosterone glucuronide, etiocholanolone glucuronide, 11beta
      hydroxy etiocholanolone glucuronide, 19-norandrosterone glucuronide, d4-19
      norandrosterone glucuronide and 1alpha-methyl-5alpha-androstan-3alpha-ol-17-one
      glucuronide are presented and the origin of typical fragment ions of the
      glycosidic and steroidal moieties is proposed, based on different derivatization
      techniques including derivatization with d18-bistrimethylsilylacetamide, methyl
      ester and trimethylsilyl ester derivatization and selected reaction monitoring.
      Typical fragmentation patterns which are related to the steroid structure are
      discussed.

PMID- 11288199
TI  - Collision-induced fragmentation of deprotonated methoxylated flavonoids, obtained
      by electrospray ionization mass spectrometry.
AB  - Electrospray operated in the negative mode was used to analyse methoxylated
      flavonoids. They were found to produce radical anions by collision-induced
      fragmentation of the aglycones. Loss of a methyl group from the deprotonated
      molecule corresponding to [M - H - 15]-* ions, as well as [M - H - 15-28]-* and
      [M - H - 15-29]- fragment ions, were found to constitute the characteristic
      fragmentation for the monomethoxylated species, whereas [M - H - 15]-*, [M - H -
      30]- and [M - H - 30-28]- were predominant for the polymethoxylated species.
      Obtained under similar conditions, the product-ion spectra of isomeric compounds
      were characteristically different. It is therefore possible to distinguish
      between methoxylated flavonoids with identical molecular mass, e.g. when
      screening plant extracts for flavonoid composition. However, comparison with
      standard compounds is necessary for the identification of unknown flavonoid
      aglycones.

PMID- 11288200
TI  - Electrospray tandem mass spectrometric study of ferrocene carbamate ester
      derivatives of saturated primary, secondary and tertiary alcohols.
AB  - The fragmentation pathways and mechanisms for 27 ferrocene carbamate esters of
      saturated alkyl primary, secondary and tertiary alcohols were investigated using
      energy-resolved electrospray tandem mass spectrometry (ES-MS/MS). The mechanisms
      that control the formation and abundance of the three product ions common to all
      the derivatives, which appear at m/z 201, 227 and 245, were elucidated. Plotting
      the relative abundances of the three product ions versus a range of center-of
      mass collision energies provided a graphical representation of the behavior of
      the fragmentation process that was directly comparable from compound to compound.
      As a result, it was possible to compare product ion spectra of the different
      derivatives to distinguish among different alcohol structural types. Straight
      chain primary alcohols were easily distinguished from tertiary alcohols. Both of
      these structural types, including positional isomers, produced product ion
      spectra that were distinct from those of beta-branched primary alcohols, or
      acyclic secondary alcohols or cyclic secondary alcohols. The latter three alcohol
      types display similar product ion spectra and therefore cannot be distinguished
      from one another on the basis of these spectra alone.

PMID- 11288201
TI  - Gabapentin quantification in human plasma by high-performance liquid
      chromatography coupled to electrospray tandem mass spectrometry. Application to
      bioequivalence study.
AB  - A rapid, sensitive and specific analytical method was developed and validated to
      quantify gabapentin in human plasma using acetaminophen as an internal standard.
      The method employs a single plasma protein precipitation. The analytes are
      chromatographed on a C4 reversed-phase chromatographic column and analyzed by
      mass spectrometry in the multiple reaction monitoring (MRM) mode. The method has
      a chromatographic run time of 4 min and a linear calibration curve over the range
      50-10 000 ng x ml(-1) (r > 0.999). The between-run precision, based on the
      relative standard deviation for replicate quality controls, was < or = 4.8 % (200
      ng x ml(-1)), 6.0% (1000 ng x ml(-1)) and 4.4% (5000 ng x ml(-1)). The between
      run accuracy was +/-2.6, 4.4 and 0.5% for the above-mentioned concentrations,
      respectively. This method was employed in a bioequivalence study of two gabentin
      capsule formulations (Progresse from Biosintetica, Brazil, as a test formulation,
      and Neurotin from Parke-Davis, as a reference formulation) in 24 healthy
      volunteers of both sexes who received a single 300 mg dose of each formulation.
      The study was conducted using an open, randomized, two-period crossover design
      with a 7-day washout interval. The 90% confidence interval (CI) of the individual
      ratio geometric mean for Progresse/Neurotin was 87.9-115.6% for AUC(0-36 h) and
      88.6-111.7% for Cmax. Since both 90% CI for AUC(0-36 h) and Cmax were included in
      the 80-125% interval proposed by the US Food and Drug Administration, Progresse
      was considered bioequivalent to Neurotin according to both the rate and extent of
      absorption.

PMID- 11288202
TI  - Impact of ion cloud densities on the measurement of relative ion abundances in
      Fourier transform ion cyclotron resonance mass spectrometry: experimental
      observations of coulombically induced cyclotron radius perturbations and ion
      cloud dephasing rates.
AB  - Fundamental research into the quantitative properties of Fourier transform ion
      cyclotron resonance mass spectrometry (FTICR-MS) has yielded interesting
      observations, especially in terms of factors affecting the accuracy of relative
      ion abundances. However, most of the previous discussions have focused on
      theoretical systems, or systems of limited scope. In this paper, we document ion
      motion attributes of a 30 spectra (six samples, five replicates each) system
      previously established as linear over two orders of magnitude. Observed behaviors
      include the perturbation of one charged species (cyclosporin A, CsA) of low ion
      density to a cyclotron orbit of greater radius than that of an almost identical,
      but slightly mass-separated species (CsG) with a higher ion density. This radial
      perturbation is attributed to the coulombic repulsion between the two ion clouds
      as they interact during the excitation process, as previously proposed by Uechi
      and Dunbar. Magnitudes of the perturbation were confirmed by making cyclotron
      radii determinations utilizing the ratio of the third-to-first harmonics for the
      charged species of interest. It was found that these radial differences can
      account for as much as a 55% signal bias in favor of CsA for a single sample and
      a >20% positive bias in the slope of the regressed data set. A second behavior
      noted that also contributes to the potential inaccuracy of relative ion abundance
      measurements is the difference in signal decay rates for CsA and CsG. Damping
      constants and initial time domain signal amplitudes were evaluated using
      segmented Fourier transforms. Discrepancies in decay rates were not expected from
      two species that have essentially identical collisional cross-sections. However,
      it has been observed that the faster decay rates are observed by the species of
      lower ion cloud density. We have attributed this differential signal decay
      phenomenon to the rates of loss of phase coherence for the two ion clouds.
      Previously, others have reported that less dense ion clouds are more susceptible
      to shearing and other disruptive forces during the course of their excited
      cyclotron motion. Our experimental evidence supports that it is the loss of cloud
      coherence that accounts for the signal loss over time, with the less dense cloud
      de-phasing more quickly. As the ion populations of the two investigated species
      near equivalence, so do their time constants.

PMID- 11288203
TI  - Minimizing analyte electrolysis in an electrospray emitter.
AB  - The electrospray (ES) ion source is a controlled-current electrolytic flow cell.
      Electrolytic reactions in the ES emitter capillary are continually ongoing to
      sustain the production of charged droplets and ultimately gas-phase ions from
      this device. Under certain circumstances, the analytes under study may be
      directly involved in these electrolytic processes. It is demonstrated that a
      simple means to minimize analyte electrolysis is to exchange the normal metal
      emitter capillary of commercial ES sources with one made of fused silica. This
      change is shown to provide an ES mass spectrometric system of similar performance
      in terms of gas-phase ion signal generated for non-electroactive analytes and
      also assures minimal oxidation of electroactive analytes even at low (2.0 microl
      x min(-1)) solution flow-rates and high (millimolar) solution electrolyte
      concentrations.

PMID- 11288204
TI  - Mass spectrometric studies of anomeric glycopyranosyl azides.
AB  - We studied the mass spectrometric behaviour of peracetylated and underivatized
      anomeric hexopyranosyl azides and 5-thioglucopyranosyl azides by means of
      different mass spectrometric techniques. The unstable molecular ions fragment
      predominantly by losing either N3 radical or N2 molecule. Loss of N2 molecule and
      the protonation of the derived nitrene were characteristic of the studied
      compounds. The presence of BF3.Et2O in the ion source is favorable for producing
      the protonated nitrene form. The protonated nitrene shows a new type of ring
      expansion rearrangement. The abundances of the [M + H - N2]+ ion makes it
      possible to identify the anomeric configuration of the azido group.

PMID- 11288205
TI  - Mass spectrometric behaviour of ion-pair precipitates of some complex anions with
      ethoxylate complex of barium.

PMID- 11288206
TI  - The intramolecular movement of deuterium in methane electron capture negative
      ionization tandem mass spectrometry.

PMID- 11288208
TI  - Respiratory diseases in the first year of life in children born to HIV-1-infected
      women.
AB  - Our objective was to describe the respiratory complications, clinical findings,
      and chest radiographic changes in the first year of life in infected and
      uninfected children born to HIV-1-infected women. We prospectively followed a
      cohort of 600 infants born to HIV-1-infected women from birth to 12 months in a
      multicenter study. Of these, 93 infants (15.5%) were HIV-1-infected, 463 were
      uninfected, and 44 were of unknown status prior to death or loss to follow-up.
      The cumulative incidence ( +/- SE) of an initial pneumonia episode at 12 months
      was 24.1 +/- 4.7% in HIV-1-infected children compared to 1.4 +/- 0.6% in HIV-1
      uninfected children (P < 0.001). The rate of Pneumocystis carinii pneumonia (PCP)
      was 9.5 per 100 child-years. The HIV-1 RNA load was not higher in the group that
      developed pneumonia in the first year vs. those who did not. Children who
      developed lower respiratory tract infections or PCP had increased rates of
      decline of CD4 cell counts during the first 6 months of life. Lower maternal CD4
      cell counts were associated with higher rates of pneumonia, and upper and lower
      respiratory tract infections. The rates of upper respiratory tract infection and
      bronchiolitis/reactive airway disease in infected children were not significantly
      different than in uninfected children. At 12 months, significantly more HIV-1
      infected than uninfected children had tachypnea and chest radiographs with
      nodular and reticular densities. There was no relationship between
      cytomegalovirus infection in the first year of life and radiographic changes or
      occurrences of pneumonia. In conclusion, despite a low incidence of PCP, rates of
      pneumonia remain high in HIV-infected children in the first year of life. The
      incidence of pneumonia in uninfected infants born to HIV-1-infected mothers is
      low. Chest X-ray abnormalities and tachypnea suggest that subacute disease is
      present in infected infants. Further follow-up is warranted to determine its
      nature.

PMID- 11288209
TI  - Predictors of a normal chest x-ray in respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) accounts for the majority of lower respiratory
      tract infections (LRTI) in infants and young children. A chest x-ray is
      frequently performed in infants with LRTI caused by RSV. The aim of this study
      was to develop and validate a prediction model to estimate the probability for a
      normal chest x-ray in children with RSV infection. For this purpose, easy
      obtainable diagnostic parameters were used. This prediction model may be applied
      to decide which patients do not require a chest x-ray. The data of 287 children
      admitted with RSV infection or diagnosed as such in the outpatient department of
      the Sophia Children's Hospital between 1992-1996 were studied. The derivation set
      comprised 232 patients (1992-1995), and the validation set contained 55 patients
      (1995-1996). A chest x-ray was designated as normal when atelectasis,
      hyperinflation, or pulmonary infiltrates were absent. In order to develop a
      prediction model, patient history and clinical and laboratory variables were
      consecutively entered into a logistic regression model according to the
      diagnostic workup that was practiced at the time. Variables with P < or = 0.10
      were retained in the model. The predictive accuracy of the multivariable models
      was examined using the area under receiver operating curve (ROC-area). In 202
      (87%) patients from the derivation set, a chest x-ray was performed. A normal
      chest x-ray could be predicted by increasing age, increasing birth weight,
      presence of rhinitis, absence of retractions, and increasing arterial oxygen
      saturation. The ROC-area was 0.80 in the derivation and validation sets. This
      prediction model was transformed into a score chart. In conclusion, a normal
      chest x-ray can accurately be predicted, using a model including easily
      obtainable patient characteristics, and clinical and laboratory variables. This
      model may be a useful tool in deciding whether or not to perform a chest x-ray in
      patients with RSV infections.

PMID- 11288210
TI  - Efficacy of nebulized epinephrine versus salbutamol in hospitalized infants with
      bronchiolitis.
AB  - We enrolled 30 infants (median age 3 months, range 1-12 months), hospitalized for
      bronchiolitis in a randomized double-blind trial, to examine the efficacy and
      safety of nebulized epinephrine compared to salbutamol. Once admitted, patients
      were treated with either nebulized 0.5 mg of an 0.1% epinephrine solution (0.5 mL
      in 3.5 mL normal saline (NS)) or 2.5 mg nebulized salbutamol (0.5 mL in 3.5 mL
      NS). They were evaluated daily before and after nebulization until discharge. The
      outcome measures used were: baseline clinical score (based on respiratory rate,
      subcostal retraction, presence of wheezing, and O2 requirement), change in
      clinical O2 score after nebulization, duration of O2 therapy, and duration of
      hospitalization. A significant improvement in the clinical score was noted on the
      first day of hospitalization in subjects receiving epinephrine (P = 0.025); that
      change was not seen in those on salbutamol (P = 0.6). Nebulized epinephrine
      decreased the baseline clinical score faster than salbutamol (P = 0.02), though
      on the fourth study day there was no significant difference between the two
      scores. On the fourth and fifth days of study there were more patients
      hospitalized in the salbutamol group than in the epinephrine group (P = 0.03 vs.
      P = 0.025). No adverse effects were associated with nebulized therapy. We
      conclude that nebulized epinephrine is a more effective agent than salbutamol in
      the initial treatment of bronchiolitis and is equally safe.

PMID- 11288211
TI  - Metal airway stent implantation in children: follow-up of seven children.
AB  - Long segment malacia of the trachea or main stem bronchi in children is not
      always suitable for surgical correction; patients may therefore remain ventilator
      dependent and/or experience severe obstructive crises. We treated 7 children
      (ages, 4 months to 9 years) with extreme structural central airway obstruction
      with stent implantations. Six were mechanically ventilated; 5 had frequent life
      threatening obstructive spells requiring deep sedation or paralysis. Diagnoses
      were: syndrome-associated tracheobronchomalacia (n = 4), malignancy infiltrating
      the carina (n = 1), congenital tracheal stenosis (n = 1), and tracheobronchial
      compression by a malpositioned aorta (n = 1). Six tracheal and 13 bronchial
      stents were endoscopically placed. The prostheses included mesh titan (n = 5),
      the newer shape memory material nitinol (n = 13), and 1 Y-shaped carina stent.
      Follow-up was reported for 7 weeks to 72 months. All patients showed marked
      improvement of their respiratory obstruction. Six children were weaned at least
      temporarily from ventilation. No significant bleeding, stenosis, or perforation
      was observed. Seven stents were changed after up to 14 months. Three children are
      well and at home. In 2 children airway stabilization was successful, but they
      later died from causes unrelated to stent placement, and 2 children died due to
      generalized airway disease. Soft metal mesh airway stents can offer a therapeutic
      option in life-threatening inoperable obstruction of the trachea and main stem
      bronchi in children.

PMID- 11288213
TI  - Benefits of thickened feeds in previously healthy infants with respiratory
      syncytial viral bronchiolitis.
AB  - Infants with respiratory syncytial virus (RSV) bronchiolitis have an increased
      risk of aspiration. The optimal feeding strategy for these patients has not been
      described. Fifteen previously healthy and clinically stable infants with RSV
      bronchiolitis underwent video-fluoroscopy studies to assess swallowing using thin
      barium. Those with abnormal studies underwent a repeat study, using barium that
      was thickened with rice cereal. Nine of 15 infants had abnormal studies with thin
      barium. Laryngeal or tracheal penetration with thin barium was seen in 3 and 2
      infants, respectively, but not with thickened barium. Aspiration of thin barium
      was seen in 4 infants, but it corrected in 3 of these 4 infants with thickened
      barium. Thickened feeds provide a simple, safe, and cost-effective intervention
      to improve swallowing dysfunction and prevent aspiration in infants with RSV
      bronchiolitis.

PMID- 11288212
TI  - Early chest radiographs in very low birth weight babies receiving corticosteroids
      for lung disease.
AB  - We set out to determine whether chest radiographs obtained in premature infants
      between 9-16 days of age are predictive for the development of chronic lung
      disease of the newborn (CLD). This was a prospective cohort study. The study
      included 40 babies who were enrolled in a randomized trial of corticosteroid
      therapy for the prevention of CLD. Chest radiographs were obtained for clinical
      indications between 9-16 and 25-35 days of age. All chest radiographs were
      assessed by a single pediatric radiologist who was unaware of the treatment
      allocation and who used a previously published scoring system devised by
      Weinstein et al. [Pediatr Pulmonol 1994;18:284-289]. The radiographic score at 9
      16 days correlated well with the radiographic score at 25-35 days of age
      (correlation coefficient, 0.69, P < or = 0.001). The scores at 9-16 days were
      significantly higher in those babies who had CLD at 28 days postnatal age (PNA)
      (P = 0.03) and at 36 weeks postmenstrual age (PMA) (P = 0.002). Using a receiver
      operator characteristic curve, we have determined that for a radiographic score
      of 3 or greater at 9-16 days, the sensitivity for CLD was 0.64, and specificity
      was 0.84. We conclude that a chest radiograph taken between 9-16 days may help
      predict which at-risk preterm infants will develop CLD.

PMID- 11288214
TI  - Bronchial trifurcation in a congenital pulmonary venolobar syndrome.
AB  - Congenital malformations of the tracheobronchal tree and the related arterial
      blood supply are a complex group of lesions in which there are abnormalities of
      the venous drainage and lung parenchyma. These malformations are examples of
      congenital pulmonary venolobar syndrome (CPVS). Tracheal trifurcation is an
      extremely rare anomaly associated with CPVS. We report on an unusual case of
      lower right extralobar sequestration connected to the trachea, plus a type I
      posterior laryngeal cleft, an aberrant systemic artery, and an anomalous route of
      the phrenic nerve. This paper discusses the place of this unusual abnormality in
      the spectrum of congenital bronchopulmonary vascular malformations.

PMID- 11288215
TI  - Late presentation of Bochdalek hernia: clinical and radiological aspects.
AB  - Three infants with late presentation of Bochdalek hernia are presented. The
      presenting symptoms were cough, intermittent vomiting, dyspnea, and cyanosis.
      Initial diagnoses of isolated paravertebral mass and foreign material aspiration
      were made in two infants, based on plain chest x-ray findings and history of the
      patients. Further radiological investigations, such as contrast upper
      gastrointestinal series or enema, computerized tomography, and magnetic resonance
      imaging of the chest, suggested the diagnosis of Bochdalek hernia. The hernia was
      found on the left side in two patients and on the right side in one. At
      operation, the stomach, small intestine, and spleen were found as herniated
      organs in one patient, ascending colon in one, and all of the small intestine
      together with ascending colon in the other. A congenital diaphragmatic defect
      should be suspected in every child presenting with unusual respiratory or
      gastrointestinal symptoms and with abnormal chest x-ray findings. The
      radiological findings vary greatly from one case to another, and even in the same
      case at different times because of differences in herniated organs and
      intermittent spontaneous reduction. The possibility of congenital diaphragmatic
      hernia should be kept in mind to avoid a wrong diagnosis, undue delay in
      diagnosis, and inappropriate treatment.

PMID- 11288216
TI  - Pulmonary artery occlusion from tuberculous lymphadenopathy in a child.
AB  - Occlusion of the pulmonary artery is a rare complication of mediastinal
      tuberculosis. We report on a 10-year-old girl who presented with a tuberculous
      pericardial effusion in whom subsequent imaging showed a totally occluded right
      pulmonary artery from tuberculous lymphadenopathy. Diagnosis was confirmed by
      polymerase chain reaction from a lymph node biopsy. Failure of medical therapy
      necessitated surgical reconstruction of her right pulmonary artery.
      Postoperatively she has normal perfusion of the right lung and normal lung
      function.

PMID- 11288217
TI  - Renal failure and vestibular toxicity in an adolescent with cystic fibrosis
      receiving gentamicin and standard-dose ibuprofen.
AB  - Gentamicin and standard-dose ibuprofen were administered to an adolescent with
      cystic fibrosis who developed renal failure and severe vestibulotoxicity. A
      contributing factor was possible suboptimal intravascular volume status. Because
      of the potential severity of this drug interaction, hydration status and renal
      and vestibular functions should be closely monitored in patients receiving
      ibuprofen and intravenous aminoglycosides concomitantly.

PMID- 11288218
TI  - Bronchoscopic instillation of surfactant in acute respiratory distress syndrome.
AB  - Abnormalities of surfactant action in acute respiratory distress syndrome (ARDS)
      result in decreased lung compliance and significant hypoxemia. Several case
      reports and small studies suggest that there is an improvement in patients with
      ARDS following the administration of surfactant. However, there is no clear-cut
      ideal method for surfactant administration. The bronchoscopic administration of
      surfactant may represent an effective method of surfactant delivery in ARDS.
      Bronchoscopic instillation offers the theoretical advantages that the surfactant
      may be distributed directly to the desired regions of the lung, a more economical
      use of surfactant, and the opportunity to lavage leaked serum proteins prior to
      instillation. Surfactant has been administered in adults with success. We present
      a case of initial improvement in oxygenation index, ventilation index, and
      mechanical ventilatory support in a pediatric patient with ARDS following the
      bronchoscopic administration of surfactant.

PMID- 11288219
TI  - Cystic fibrosis and Down's syndrome: not always a poor prognosis.
AB  - A child developed a bronchiolitis-like illness and was found to have mosaic
      Down's syndrome (diagnosed on karyotype) and also cystic fibrosis, diagnosed on
      the basis of a high sweat osmolality (247 mosmoles/kg sweat; normal, 62-137) and
      a homozygous delta F508 genotype. Despite two potentially life-threatening
      conditions, the child is doing well at the age of 7 years, despite pancreatic
      insufficiency.

PMID- 11288220
TI  - Role of inhaled long-acting beta-agonists.

PMID- 11288221
TI  - Antireflux surgery in children suffering from reflux-associated respiratory
      disease?

PMID- 11288222
TI  - Are long-acting beta-agonists the "winning team" in childhood asthma?

PMID- 11288224
TI  - [Dealing with aggression and violence].

PMID- 11288225
TI  - [Managing violence].

PMID- 11288226
TI  - [Isolation and video surveillance, ethic considerations].

PMID- 11288227
TI  - [An effective model of practice without contention].

PMID- 11288228
TI  - [Learning to manage one's own aggression].

PMID- 11288229
TI  - [The syndrome of burnout in the relation with aides].

PMID- 11288231
TI  - [The influence of the relieving-dietetic therapy on the calculi acoustic
      properties in biliary calculous disease].
AB  - In 45 patients with biliary calculous disease the relieving-dietetic therapy
      course was performed. The fragmentation or lysis of echopermeable echononsolid,
      echononpermeable echononsolid, echopermeable echosolid calculi was established.
      There was not noted fragmentation of echononpermeable echosolid calculi.

PMID- 11288230
TI  - [A delicious enigma].

PMID- 11288232
TI  - [The ways of the results improvement in surgical treatment of the right side
      colonic decompensated obstruction].
AB  - There were operated on 87 patients with an acute ileus, caused by stenosing tumor
      of the right colon. In 49 patients the shunting ileotransversoanastomosis was
      formed and in 30--the right-sided hemicolectomy with primary anastomosis and
      decompressive terminal ileostomy according to method of clinic was performed.
      After application of conventional method postoperative mortality was 22.4% and
      frequency of postoperative complications--36.7%, and after application of the
      proposed method--13.3 and 26.6% accordingly.

PMID- 11288233
TI  - [Interrelationship of the immune status with the degree of reactive anxiety in
      patients with gastroduodenal disease].
AB  - Interrelationship of the immune state of patients with the reactive anxiety
      degree in patients suffering gastroduodenal ulcer disease was established. The
      most pronounced inhibition of the immunity cell link along with moderate
      activation of its humoral link was noted in patients with low degree of anxiety,
      and less pronounced one--with high degree of anxiety, in patients with middle
      degree of anxiety the changes were absent.

PMID- 11288234
TI  - [The prognosis of the traumatic disease course in polytrauma].
AB  - Comparative estimation of the state severity in 427 injured persons with
      polytrauma according to B[symbol: see text]X-M[symbol: see text] (OP)--C[symbol:
      see text]6, ISS, PTS scales was done. The lack of their efficacy was established.
      The method of the polytrauma severity estimation, concerning the injuries mutual
      aggravation syndrome as the main pathogenetic cause, was proposed. Six criteria,
      determined with the help of factor analysis, are estimated: the injured anatomic
      parts quantity, the anatomic injury severity index, the level of consciousness,
      systolic arterial pressure, age of the injured person, the period before the
      onset of the antishock therapy conduction. The total account of the criteria
      values are inscribed in the formula and are noted in special form of the
      standardized scale. The method permits to estimate the politrauma severity, to
      prognosticate the complications, the syndrome of polyorganic dysfunction
      occurrence and the mortality rate with 95% accuracy.

PMID- 11288235
TI  - [Alloplasty efficacy in the treatment of giant postoperative and recurrent
      abdominal hernia].
AB  - Experience concerning the treatment of 352 patients with spacious and giant
      recurrent and postoperative abdominal hernia was summarized. In 289 patients
      (basic group) polypropilenic net was insewn for the musculoaponeurotic defect of
      anterior abdominal wall closure, permitting to close the hernial hiatus without
      tension on the tissues. In 63 patients (control group) the hernial hiatus plasty
      was done using the tissues of their own. The recurrency in basic group had
      occurred in 3 (1%) of patients and in the control one--in 15 (23.8%).

PMID- 11288236
TI  - [Experience of serotonin application in the treatment complex of the lower
      extremities chronic atherosclerotic ischemia].
AB  - In 35 patients with chronic atherosclerotic ischemia of the lower extremities
      serotonin was applied in complex of treatment. Significant enhancement of
      volumetric blood flow, of the oxygen partial pressure and of rheovasographic
      index as well were noted. Clinically positive effect of the treatment was
      manifested by enhancement of the distance passed without pain, the extremity
      getting warmer and the pain cessation in rest.

PMID- 11288237
TI  - [The efficacy of reoperation of the patients with diabetic foot].
AB  - The causes and results of reoperation for diabetic foot in 116 patients during
      three years were analyzed.

PMID- 11288238
TI  - [Morphological changes of lymphatic system in patients with the lymphedema of
      lower extremities].
AB  - Morphological changes in inguinal lymph nodes, lymphatic collector and
      subcutaneous space were studied up in patients with the lower extremities
      lymphoedema. While the lower extremities lymphoedema occurs in inguinal lymph
      nodes the connective tissues spreading in two variants is observed. In the first
      one fibroblasts and collagen fibres appears in medullar substance (chordae
      medullaris and medullar sinuses) and in the second the sclerosis process begins
      from cortical plateau and paracortical zone. It is expedient to include the
      intraarterial infusion of the xenospleen preparations in complex of treatment of
      patients with initial stage of the lower extremities lymphoedema, especially in
      the absence of possibility to proceed with microsurgical intervention and the
      erysipelas presence in anamnesis.

PMID- 11288239
TI  - [The treatment of thyroid gland cyst using ND-YAG laser].
AB  - The results of treatment of 23 patients with the thyroid gland cyst was
      summarized. Laser photocoagulation was performed under ultrasonographic control.
      Peculiarities of the treatment performance using laser for the thyroid gland cyst
      with more than 10 ml volume were established. Twenty two (95.7%) patients had
      recovered and in one (4.3%)--the state improvement was noted. In laser
      photocoagulation for the cystically-transformed nodes the reduction or
      disappearance of residual nodal tissue was noted, there were no postoperative
      complications.

PMID- 11288240
TI  - [The pulmonary resection for tuberculosis in patients with severe diabetes
      mellitus].
AB  - Peculiarities of preoperative preparation and of pulmonary resection performance,
      postoperative period management in 82 patients with pulmonary tuberculosis and
      severe diabetes mellitus were analyzed. In 29.27% of patients the complications
      occurred. After the operation 4.87% of patients died. Positive clinical effect
      was noted in 95.13% of patients, 86.04% of patients were recovered during 1-20
      yrs period of follow-up. The diabetes mellitus course severity had reduced. In
      further follow-up period the pulmonary tuberculosis reactivation in 9.3% was
      noted.

PMID- 11288241
TI  - [Application of the puncture laser diskectomy in the treatment of multiple
      hernias of sacro-iliac intervertebral disks].
AB  - In 144 patients with discogenic lumbosacralic radiculitis the puncture laser
      discectomy was performed on several levels independently or in combination with
      open operative intervention. High efficacy of treatment was noted.

PMID- 11288242
TI  - [Comparative efficacy of low molecular heparin (fraxiparine), non-fractionized
      heparin and anti-aggregate therapy in the prophylaxis complex for thromboembolic
      complications after surgical interventions performed for oncological disease].
AB  - Thromboembolism is one of the most frequent postoperative complications, which
      lead to exitus letalis in many of the patients. The thromboembolism occurrence is
      the most frequent in oncological diseases. Anticoagulants of direct action the
      nonfractionized heparin and low molecular weight heparins are applied for
      prophylaxis of thromboembolic complications. Their usage in combination with
      antiaggregative preparations is undesirable because of the bleeding occurrence
      threat. Comparative studying of prophylactic action and the haemorrhagic
      complications frequency under the usage of heparin, fraxiparin and
      antiaggregative preparations was performed in 462 patients. Maximal activity of
      low molecular weight heparins vs such of nonfractionized heparin and
      antiaggregative preparations was proved. The trustworthy enhancement of the
      bleeding frequency and of the blood coagulating system was not noted in the
      combined application of fraxiparin and antiaggregative preparations.

PMID- 11288243
TI  - [The restoration of colonic continuity after Hartmann's operation].
AB  - The experience of restorational intervention with formation of duplicature
      (invagination) anastomosis after Hartmann's operation in 45 patients with
      complicated cancer recti and colonic cancer was summarized. Complications had
      occurred in 9.8% of observations, one patient died.

PMID- 11288244
TI  - [The primary-multiple malignant tumors inpatients with mammary gland cancer].
AB  - Of 5073 patients with mammarial gland cancer (MGC) observed during 20 years of
      follow-up in 409 (8.1%) polyneoplasia was revealed. In 21 (5.1%) of 409 patients
      three polyorganic primary tumors and more were revealed. In 108 (26.4%) of them
      the primarily-multiple tumors were synchronous, in 301 (73.6%)--metachronous.
      Most frequently MGC occurred in conjunction with tumors of genital and digestive
      systems, which have the highest frequency in population. In the other organs
      polyneoplasia was revealed significantly rarely.

PMID- 11288245
TI  - [The affection of the nervous system in patients with malignant tumor of testis].
AB  - Clinical observations of intracranial metastases of seminoma testis were
      performed together with studying of their morphological types and cerebral
      localization.

PMID- 11288247
TI  - [TNM classification of the intestinal malignancies].

PMID- 11288246
TI  - [The modelling of the testis circulation disorders and its morpho-functional
      status in partial ischemia].
AB  - Morphofunctional state of testis in partial ischemia, modelled by bandaging of
      its artery and vein down to 1/2 of their diameter, was studied up in experiment.
      The importance of vascular factor in the hypogonadism and male sterility
      occurrence was established.

PMID- 11288248
TI  - [Controversial issues in the diagnosis and treatment of acute nondestructive
      appendicitis].

PMID- 11288249
TI  - [The partial portosystemic shunting and its hemodynamic consequences].
AB  - Complex hemodynamical investigations were done in 32 patients in 1985-1999 yr.
      period before the operation, in 6-8 and 12-24 mo after performance of the partial
      portosystemic shunting operation (in 8 patients mesentericocaval anastomosis was
      formed, in 10--central splenorenal anastomosis, in 12--splenorenal anastomosis
      side to side and in 2--lowermesentericorenal anastomosis). The performance of
      shunting operation had promoted the lowering of the blood flow volumetric
      velocity and of the pressure in v. cava as well, its diameter reduction, the
      lowering of general hepatic blood flow. The lowering of blood flow in the v. cava
      system after the shunting operation performance caused the arterial hepatic blood
      flow enhancement occurrence.

PMID- 11288250
TI  - [The role of the test control in the process of training of surgeons].

PMID- 11288251
TI  - [Acute pancreatitis (epidemiology, etiology, mortality)].

PMID- 11288252
TI  - [A method of treatment of necrotic pancreatitis].

PMID- 11288253
TI  - [A method of puncture of gallbladder].

PMID- 11288254
TI  - [Application of trans-sternum occlusion of the main bronchus stump using
      transdiaphragmatic omentopexy for post-pneumonectomy bronchial fistula].

PMID- 11288255
TI  - [Tactics of surgeon in purulent-necrotic complications of an acute pancreatitis].

PMID- 11288256
TI  - [Prophylaxis and treatment of the ingrown nail in patients with diabetes
      mellitus].

PMID- 11288257
TI  - [The prolonged intestinal irrigation in a child with Hirschsprung disease
      complicated by enterocolitis].

PMID- 11288258
TI  - [Prolonged spinal cord anesthesia with morphine and clofelin].

PMID- 11288259
TI  - [Complications of acute forms pancreatitis].

PMID- 11288260
TI  - [A method of treatment of hydronephrosis of the horseshoe-like kidney in a
      child].

PMID- 11288261
TI  - [Acute appendicitis in patient with intestinal yersinosis].

PMID- 11288262
TI  - [Cysts of abdominal cavity and retroperitoneal space originated from mucosal
      bursas of posterior abdominal wall].

PMID- 11288263
TI  - [Observation of giant cyst of retroperitoneal space].

PMID- 11288264
TI  - [Prognosis of an acute pancreatitis and its postop course].
AB  - Dynamical investigation of clinical and laboratory indexes in 108 patients, in
      whom 155 operative interventions were performed for destructive pancreatitis, was
      done. The statistically trustworthy difference in the indexes obtained in the
      patients was established after performance of the first operation and in those
      who were reoperated on.

PMID- 11288265
TI  - [Possibilities of x-ray methods in diagnosis of an acute pancreatitis and its
      local complications].
AB  - The ray methods of investigation were applied in 182 patients with an acute
      pancreatitis (AP). In 28% of patients local complications of AP were revealed:
      pseudocyst, abscess, pancreatic gland phlegmon, the gastric wall infiltration and
      ulceration, paracolic infiltrate and colonic obstruction, biliary hypertension,
      portal hypertension, subcapsular and parenchymatous splenic hematoma.

PMID- 11288266
TI  - [Results of partial shunting in liver cirrhosis].
AB  - Complex hemodynamical investigations were conducted in 32 patients before the
      operation and after performance of partial portosystemic shunting (in 8-
      mesentericocaval anastomosis was done, in 10--central splenorenal one, in 12-
      splenorenal side-to-side, in 2--lowermesenterial-renal). The formation of
      anastomosis 8-10 mm in diameter had promoted the sufficient reduction of pressure
      in v. porta, preservation in it the hepatopetal blood flow, prophylaxis of
      uncontrolled occurrence of portosystemic encephalopathy, had secured the stable
      hepatic function during 36 months.

PMID- 11288267
TI  - [Thoraco-abdominal wound in peaceful time].
AB  - The results of treatment of 63 injured persons with thoracicoabdominal trauma
      were analyzed. Injured persons with severe trauma and pronounced infringements of
      hemodynamic (41.25%); with severe injury of inferior organs and stable
      hemodynamical indexes (47.62%), light injury (11.12%) were detailed. Algorithm of
      curative-diagnostical measures for every group was elaborated. Among the injured
      persons 11 (17.46%) died.

PMID- 11288268
TI  - [Methods of inversion closure of transient colostomy].
AB  - The method of inversive excision of colostomy, securing access to noninflamed
      tissues of intestine and pericolostomic region for consequent suturing made in
      accordance to requirements. While using the method purulent-inflammatory
      complications had occurred in less than 5% of patients and insufficiency of
      anastomotic sutures--in 3.4%.

PMID- 11288269
TI  - [Application of systemic enzyme therapy in combined treatment of patients with
      pulmonary cancer and malignant thymoma].
AB  - The systemic enzymotherapy using Wobe-Mugos E in the combined treatment of 32
      patients with pulmonary cancer and of 21 patients with malignant thymoma was
      applied. After the chemotherapy and radiotherapy conduction the reduction of the
      postoperative septic-purulent complications, the pneumofibrosis occurrence
      prophylaxis was noted.

PMID- 11288270
TI  - [Prophylaxis of thromboembolic complications in patients with destructive
      pulmonary tuberculosis and diabetes mellitus].
AB  - The methods of the hemostasis correction in 118 patients with destructive
      pulmonary tuberculosis (DPT) and diabetes mellitus (DM) were determined. Along
      with dietetic and insulinotherapy, chemotherapy, there were administered
      anticoagulants of direct and indirect action, rheopolyglucin, effective
      electrostimulation of the back and lower extremities muscles, ultra-violet
      irradiation of blood, electrophoresis of 6% solution of sodium salicylate and
      5000 U of heparin on pancreatic region according to the method proposed.

PMID- 11288271
TI  - [Peculiarities of clinical diagnosis of the thyroid gland cancer invading trachea
      and larynx].
AB  - The experience of diagnosis of the thyroid gland (TG) spreaded cancer in 153
      patients was summarized. Optimal differentiated surgical methods were applied
      depending on the affection severity of the main respiratory ways. Combined
      resection TG with part of trachea (larynx) in 18 patients was done, in 96-
      thyroidectomy, in 39--palliative intervention.

PMID- 11288272
TI  - [Endoprosthesis of mammary glands using hydrogel prosthesis PAAG "Interfall"].
AB  - The results of the mammarial glands endoprosthesis in 60 women patients, of them
      in 57--with prostheses PAAG "Interfall", applied for the first time, were
      analyzed. The occurrence frequency for postoperative complications was 19%,
      including sensitivity disorders of papillo-areolar complex were noted in 14% of
      observations and seroma--in 5%. Preoperative, intraoperative, postoperative
      tactic of management of women patients, operated for the first time and with
      purulent-septic complications occurring after mammoplasty using application of
      gel and prostheses PAAG "Interfall" was elaborated.

PMID- 11288273
TI  - [Raising of the treatment efficacy of renal colic and prophylaxis of acute
      calculous pyelonephritis in patient with ureterolithiasis].
AB  - In 116 patients with renal colic, caused by stones of ureters, conservative
      treatment with application of hyperbaric oxygenation (HBO) was conducted. Under
      the influence of oxygenotherapy during 3 days obstruction of the urinary tracts
      in all patients had disappeared as well as acute urostasis, clinic symptoms of
      the renal colic, progress of an acute infectious-inflammatory process stopped,
      complications were eliminated. Echo-positive subjects had disappeared from
      kidneys, in one patient renal calculus had dissolved, in 5--calculi had reduced
      in size and fragmentated, in 9--had not changed. In 108 patients the ureters had
      freed from calculi, in 8--calculi had reduced in size and migrated in distal
      direction.

PMID- 11288275
TI  - [Treatment of osteomyelitis of antebrachial bones in children].
AB  - The clinic, diagnosis, principles of treatment, remote results of treatment in 50
      children with osteomyelitis of the antebrachial bones were adduced.

PMID- 11288274
TI  - [Surgical correction of intrathoracic compression of respiratory ways due to
      double aortal arch in children].
AB  - In 1982-1999 period 49 children aged 1.5 mo-14 yrs with vascular ring anomaly
      were examined. In 28 of them the double aortal arch (DAA), causing intrathoracic
      compression of respiratory ways, was revealed. Surgical correction of DAA was
      done in 27 patients. Optimal surgical access is left-sided lateral thoracotomy
      along third or fourth intercostal space. Tactics of surgical intervention was
      differentiated one depending on anatomo-topographic peculiarities of aortal arch
      morphology, its branches and age of a child. Aortopexy was done together with
      vascular failure correction for concomitance with secondary tracheomalacia and
      Kommerel's diverticulum.

PMID- 11288276
TI  - [Experience of treatment of an acute hematogenic osteomyelitis in children].
AB  - The results of treatment of 215 patients with an acute gematogenic osteomyelitis
      (AGO) aged from newborn to 15 years were analyzed. The main principles and
      methods of the AGO treatment, elaborated and introduced in the clinic, were
      suggested. The osteotomy method with introduction of two drains for the affection
      focus sanation in the senior age children was proposed. Complications had
      occurred in 13% of patients, transition into chronic form was noted in 8%.

PMID- 11288277
TI  - [Retrospective estimation of immune status in children with acute hematogenic
      osteomyelitis].
AB  - The immune state estimation in 45 children with an acute gematogenic
      osteomyelitis was done for the disease course prognosis and the treatment tactic
      choice. Two groups with duration of treatment up to forty days and from 41 to 160
      days were delineated. The immunologic investigation data permitted to
      prognosticate the disease course duration and to correct the treatment timely.
      Slow immune reaction of organism in patients was caused by the disease severity
      and presence of complications.

PMID- 11288278
TI  - [Analysis of complications of operation for appendicular peritonitis in
      children].
AB  - Complications, occurred after the operation for appendicular peritonitis in
      children, were analyzed. The frequency of the complications occurrence in
      patients with an acute catarrhal appendicitis had constituted 1.4%, with
      phlegmonous one--3.5%, gangrenous--12.1%, gangrenous appendicitis with local
      restricted peritonitis--18.9%, with diffuse purulent peritonitis--42%. The
      dependence of the complications frequency on character and severity of primary
      changes in abdominal cavity was established.

PMID- 11288279
TI  - [Total endoprosthesis of knee joint for the severe deformity of the femoral and
      tibial condyles].
AB  - The method of knee joint endoprosthesis for its pronounced deformity was
      proposed. As a transplant there was applied the ceramic hydroxiapatite,
      manufactured according to special technology. The implant was fixed on the
      transplant adjusted.

PMID- 11288280
TI  - [Application of mini-invasive osteosynthesis in the treatment of the fracture of
      the femoral diaphysis].
AB  - Experience of operative treatment of the diaphysis femoris fracture in 673
      patients was presented. Majority of operations were performed in 6-24 hours after
      the trauma occurrence. In 517 observations generally accepted method of
      osteosynthesis, and in 156--miniinvasive one, were applied. Results of
      intervention in 1-4 years in 391 patients were studied. Good result in 87.5%,
      satisfactory--in 9.9%, poor--in 3.3% were noted. Authors recommend to conduct
      operative treatment of the diaphysis femoris fracture as early as possible.
      Miniinvasive osteosynthesis is the preferable method of osteosynthesis in injured
      persons with severe polytrauma, multicomminuted and segmental fracture.

PMID- 11288281
TI  - [Osteosynthesis in fractures of proximal epiphyseal metaphysis of the femur].
AB  - The results of operative treatment of the proximal epimetaphysis femoris fracture
      in elderly patients were analyzed. The unified table of optimal methods of their
      operative treatment was elaborated.

PMID- 11288282
TI  - [The role of the intestine in the pathogenesis of the multi-organ dysfunction
      syndrome in diffuse peritonitis].
AB  - Extraction of oxygen (O2), ultrastructural organization of intestinal macrophages
      and translocation of microorganisms were studied on 50 male rats of Wistar line
      in 2, 6, 12, 24 and 48 hours after the stimulation operation performance (control
      group) and modelling of an acute purulent peritonitis (APP)--basic group.
      Increase of common and lowering of intestinal extraction of O2 in early terms of
      the APP occurrence, accompanied by intensive reproduction of microorganisms and
      change of intestinal biocenosis, was noted. These infringements correlated with
      translocation of microorganisms through mesenteric lymphatic nodes--ductus
      toracicus--systemic blood flow (basic way) in term up to 24 hours and through
      portal vein--hepar--systemic blood flow (additional way)--up to 48 hours after
      the APP beginning.

PMID- 11288283
TI  - [Liver transplantation].

PMID- 11288284
TI  - [Changes in immune state in patients with duodenal ulcer disease].
AB  - There were examined 73 patients with giant ulcer (GU) of the duodenum and 62-
      with the smaller size ulcer of the duodenum. In majority of patients essential
      disorders of immune state were revealed: reduction of the T-lymphocytes quantity,
      disbalance of their subpopulation composition, the rise of the circulating immune
      complexes level, activization of autoimmune reactions. In patients with duodenal
      GU immune disorders were more pronounced, than in the presence of the smaller
      size duodenal ulcer. Maximum changes of the immune status were observed in
      patients with complications of duodenal GU--perforation, penetration,
      haemorrhage.

PMID- 11288285
TI  - [Modern trends in the treatment of destructive pancreatitis].

PMID- 11288286
TI  - [Intraoperative decompression and intestinal lavage].

PMID- 11288287
TI  - [Expediency of "obligatory" peritoneal cavity drainage and prophylaxis of the
      anterior abdominal wall wound healing after laparoscopic cholecystectomy].

PMID- 11288288
TI  - [Choice of antibiotic for the treatment of acute pancreatitis through the method
      of investigation of leukocyte sensitivity].

PMID- 11288289
TI  - [Surgical correction of inguinal hernia in boys of the first year of life].

PMID- 11288290
TI  - [Plastic surgery of postoperative abdominal hernia using auto-dermal flap].

PMID- 11288291
TI  - [Successful treatment of the chronic iliac artery aneurysm rupture after
      arthrodesis of coxofemoral joint].

PMID- 11288292
TI  - [Successful treatment of malignant pulmonary histiocytoma in a child].

PMID- 11288293
TI  - [Successful treatment of Bouveret syndrome in elderly woman patient].

PMID- 11288294
TI  - [Observation of cancer of triple localization].

PMID- 11288295
TI  - [Observation of echinococcosis of the mediastinum].

PMID- 11288296
TI  - [The transverse colon descending via the small intestine mesentery in rectal
      cancer]].

PMID- 11288297
TI  - [Comparative estimation of the prognosis methods for an early recurrency of
      hemorrhage of ulcerative genesis].
AB  - There were revealed the occurrence risk factors for an early recurrence of
      hemorrhage of ulcer etiology, the method of mathematical prognosis was suggested
      with 78.8% authenticity. The programm of computeric prognosis, basing on
      "neuronic nets" with 91% authenticity was elaborated. It was established that
      computeric prognosis is more authentic and perspective method in comparison with
      mathematic one.

PMID- 11288298
TI  - An evaluation of flare combustion efficiency using open-path Fourier transform
      infrared technology.
AB  - Open-path Fourier transform infrared (OP-FTIR) technology was used to evaluate
      the combustion efficiency of a flare for comparison to several combustion models.
      Most flares have been considered an effective method for destroying organic
      compounds and anything that burns. As the Btu content of the flare gas is
      reduced, the combustion efficiency may also be reduced. Recent studies have
      suggested that lower Btu flares may have efficiencies as low as 65%. In addition,
      models have been developed to predict the effect of wind speed and stack
      discharge velocity on the combustion efficiency. This study was conducted on a
      low-Btu flare gas that is primarily CO. While the models would predict
      efficiencies as low as 30%, the sampling using OP-FTIR showed most combustion
      efficiencies well above 90%. Three methods were used to track combustion
      efficiency: monitoring the ratio of CO to CO2, monitoring the ratio of CO to
      tracer gas, and dispersion modeling. This study was complicated by the presence
      of two flare stacks, thus two tracer gases were used--SF6 and CF4. A method was
      developed for distinguishing between the two stacks and quantifying the
      efficiency in each stack.

PMID- 11288299
TI  - Characterization of emissions from diffusion flare systems.
AB  - Emissions from flares typical of those found at oil-field battery sites in
      Alberta, Canada, were investigated to determine the degree to which the flared
      gases were burned and to characterize the products of combustion in the
      emissions. The study consisted of laboratory, pilot-scale, and field-scale
      investigations. Combustion of all hydrocarbon fuels in both laboratory and pilot
      scale tests produced a complex variety of hydrocarbon products within the flame,
      primarily by pyrolytic reactions. Acetylene, ethylene, benzene, styrene, ethynyl
      benzene, and naphthalene were some of the major constituents produced by
      conversion of more than 10% of the methane within the flames. The majority of the
      hydrocarbons produced within the flames of pure gas fuels were effectively
      destroyed in the outer combustion zone, resulting in combustion efficiencies
      greater than 98% as measured in the emissions. The addition of liquid hydrocarbon
      fuels or condensates to pure gas streams had the largest effect on impairing the
      ability of the resulting flame to destroy the pyrolytically produced
      hydrocarbons, as well as the original hydrocarbon fuels directed to the flare.
      Crosswinds were also found to reduce the combustion efficiency (CE) of the co
      flowing gas/condensate flames by causing more unburned fuel and the pyrolytically
      produced hydrocarbons to escape into the emissions. Flaring of solution gas at
      oil-field battery sites was found to burn with an efficiency of 62-82%, depending
      on either how much fuel was directed to flare or how much liquid hydrocarbon was
      in the knockout drum. Benzene, styrene, ethynyl benzene, ethynyl-methyl benzenes,
      toluene, xylenes, acenaphthalene, biphenyl, and fluorene were, in most cases, the
      most abundant compounds found in any of the emissions examined in the field flare
      testing. The emissions from sour solution gas flaring also contained reduced
      sulfur compounds and thiophenes.

PMID- 11288300
TI  - A method for removal of CO from exhaust gas using pulsed corona discharge.
AB  - An experimental study of the oxidation of CO in exhaust gas from a motorcycle has
      been carried out using plasma chemical reactions in a pulsed corona discharge. In
      the process, some main parameters, such as the initial CO concentration,
      amplitude and frequency of pulses, residence time, reactor volume, and relative
      humidity (RH), as well as their effects on CO removal characteristics, were
      investigated. O3, which is beneficial to reducing CO, was produced during CO
      removal. When the exhaust gas was at ambient temperature, more than 80% CO
      removal efficiency was realized at an initial concentration of 288 ppm in a
      suitable range of the parameters.

PMID- 11288301
TI  - Impact of microenvironmental nitrogen dioxide concentrations on personal
      exposures in Australia.
AB  - Indoor and outdoor NO2 concentrations were measured and compared with
      simultaneously measured personal exposures of 57 office workers in Brisbane,
      Australia. House characteristics and activity patterns were used to determine the
      impacts of these factors on personal exposure. Indoor NO2 levels and the presence
      of a gas range in the home were significantly associated with personal exposure.
      The time-weighted average of personal exposure was estimated using NO2
      measurements in indoor home, indoor workplace, and outdoor home levels. The
      estimated personal exposures were closely correlated, but they significantly
      underestimated the measured personal exposures. Multiple regression analysis
      using other nonmeasured microenvironments indicated the importance of
      transportation in personal exposure models. The contribution of transportation to
      the error of prediction of personal exposure was confirmed in the regression
      analysis using the multinational study database.

PMID- 11288302
TI  - Assessment of the effects of sugar cane plantation burning on daily counts of
      inhalation therapy.
AB  - This study was designed to evaluate the association between sugar cane plantation
      burning and hospital visits in Araraquara in the state of Sao Paulo, Brazil. From
      June 1 to August 31, 1995, the daily number of visits of patients who needed
      inhalation therapy in one of the main hospitals of the city was recorded and used
      as health impairment estimation. Sedimentation of particle mass (the amount of
      particles deposited on four containers filled with water) was measured daily. The
      association between the weight of the sediment and the number of visits was
      evaluated by means of Poisson regression models controlled for seasonality,
      temperature, day of the week, and rain. We found a significant and dose-dependent
      relationship between the number of visits and the amount of sediment. The
      relative risk of visit associated with an increase of 10 mg in the sediment
      weight was 1.09 (1-1.19), and the relative risk of an inhalation therapy was 1.20
      (1.03-1.39) on the most polluted days (fourth quartile of sediment mass). These
      results indicate that sugar cane burning may cause deleterious health effects in
      the exposed population.

PMID- 11288304
TI  - Interaction of temperature, humidity, driver preferences, and refrigerant type on
      air conditioning compressor usage.
AB  - Recent studies have shown large increases in vehicle emissions when the air
      conditioner (AC) compressor is engaged. Factors that affect the compressor-on
      percentage can have a significant impact on vehicle emissions and can also lead
      to prediction errors in current emissions models if not accounted for properly.
      During 1996 and 1997, the University of California, Riverside, College of
      Engineering-Center for Environmental Research and Technology (CE-CERT) conducted
      a vehicle activity study for the California Air Resources Board (CARB) in the
      Sacramento, CA, region. The vehicles were randomly selected from all registered
      vehicles in the region. As part of this study, ten vehicles were instrumented to
      collect AC compressor on/off data on a second-by-second basis in the summer of
      1997. Temperature and humidity data were obtained and averaged on an hourly
      basis. The ten drivers were asked to complete a short survey about AC operational
      preferences. This paper examines the effects of temperature, humidity,
      refrigerant type, and driver preferences on air conditioning compressor activity.
      Overall, AC was in use in 69.1% of the trips monitored. The compressor was on an
      average of 64% of the time during the trips. The personal preference settings had
      a significant effect on the AC compressor-on percentage but did not interact with
      temperature. The refrigerant types, however, exhibited a differential response
      across temperature, which may necessitate separate modeling of the R12
      refrigerant-equipped vehicles from the R134A-equipped vehicles. It should be
      noted that some older vehicles do get retrofitted with new compressors that use
      R134A; however, none of the vehicles in this study had been retrofitted.

PMID- 11288303
TI  - Measurement of odor intensity by an electronic nose.
AB  - The possibility of using electronic noses (ENs) to measure odor intensity was
      investigated in this study. Two commercially available ENs, an Aromascan A32S
      with conducting polymer sensors and an Alpha M.O.S. Fox 3000 with metal oxide
      sensors, as well as an experimental EN made of Taguchi-type tin oxide sensors,
      were used in the experiments. Odor intensity measurement by sensory analysis and
      EN sensor response were obtained for samples of odorous compounds (n-butanol,
      CH3COCH3, and C2H5SH) and for binary mixtures of odorous compounds (n-butanol and
      CH3COCH3). Linear regression analysis and artificial neural networks (ANN) were
      used to establish a relationship between odor intensity and EN sensor responses.
      The results, suggest that large differences in sensor response to samples of
      equivalent odor intensity exist and that sensitivity to odorous compounds varies
      according to the type of sensors. A linear relationship between odor intensity
      and averaged sensor response was found to be appropriate for the EN based on
      conducting polymer sensors with a correlation coefficient (r) of 0.94 between
      calculated and measured odor intensity. However, the linear regression approach
      was shown to be inadequate for both ENs, which included metal oxide-type sensors.
      Very strong correlation (r = 0.99) between measured odor intensity and calculated
      odor intensity using the ANN developed were obtained for both commercial ENs. A
      weaker correlation (r = 0.84) was found for the experimental instrument,
      suggesting an insufficient number of sensors and/or not enough diversity in
      sensor responses. The results demonstrated the ability of ENs to measure odor
      intensity associated with simple mixtures of odorous compounds and suggest that
      ANN are appropriate to model the relationship between odor intensity measurement
      and EN sensor response.

PMID- 11288305
TI  - A life-cycle comparison of alternative automobile fuels.
AB  - We examine the life cycles of gasoline, diesel, compressed natural gas (CNG), and
      ethanol (C2H5OH)-fueled internal combustion engine (ICE) automobiles. Port and
      direct injection and spark and compression ignition engines are examined. We
      investigate diesel fuel from both petroleum and biosources as well as C2H5OH from
      corn, herbaceous bio-mass, and woody biomass. The baseline vehicle is a gasoline
      fueled 1998 Ford Taurus. We optimize the other fuel/powertrain combinations for
      each specific fuel as a part of making the vehicles comparable to the baseline in
      terms of range, emissions level, and vehicle lifetime. Life-cycle calculations
      are done using the economic input-output life-cycle analysis (EIO-LCA) software;
      fuel cycles and vehicle end-of-life stages are based on published model results.
      We find that recent advances in gasoline vehicles, the low petroleum price, and
      the extensive gasoline infrastructure make it difficult for any alternative fuel
      to become commercially viable. The most attractive alternative fuel is compressed
      natural gas because it is less expensive than gasoline, has lower regulated
      pollutant and toxics emissions, produces less greenhouse gas (GHG) emissions, and
      is available in North America in large quantities. However, the bulk and weight
      of gas storage cylinders required for the vehicle to attain a range comparable to
      that of gasoline vehicles necessitates a redesign of the engine and chassis.
      Additional natural gas transportation and distribution infrastructure is required
      for large-scale use of natural gas for transportation. Diesel engines are
      extremely attractive in terms of energy efficiency, but expert judgment is
      divided on whether these engines will be able to meet strict emissions standards,
      even with reformulated fuel. The attractiveness of direct injection engines
      depends on their being able to meet strict emissions standards without losing
      their greater efficiency. Biofuels offer lower GHG emissions, are sustainable,
      and reduce the demand for imported fuels. Fuels from food sources, such as
      biodiesel from soybeans and C2H5OH from corn, can be attractive only if the co
      products are in high demand and if the fuel production does not diminish the food
      supply. C2H5OH from herbaceous or woody biomass could replace the gasoline burned
      in the light-duty fleet while supplying electricity as a co-product. While it
      costs more than gasoline, bioethanol would be attractive if the price of gasoline
      doubled, if significant reductions in GHG emissions were required, or if fuel
      economy regulations for gasoline vehicles were tightened.

PMID- 11288306
TI  - Evaluation of time-resolved PM2.5 data in urban/suburban areas of New Jersey.
AB  - Time-resolved data is needed for public notification of unhealthful air quality
      and to develop an understanding of atmospheric chemistry, including insights
      important to control strategies. In this research, continuous fine particulate
      matter (PM2.5) mass concentrations were measured with tapered element oscillating
      microbalances (TEOMs) across New Jersey from July 1997 to June 1998. Data
      features indicating the influence of local sources and long-distance transport
      are examined, as well as differences between 1-hr maxima and 24-hr average
      concentrations that might be relevant to acute health effects. Continuous mass
      concentrations were not significantly different from filter-collected gravimetric
      mass concentrations with 95% confidence intervals during any season. Annual mean
      PM2.5 concentrations from July 1997 to June 1998 were 17.3, 16.4, 14.1, and 15.3
      micrograms/m3 at Newark, Elizabeth, New Brunswick, and Camden, NJ, respectively.
      Monthly averaged 24- and 1-hr daily maximum PM2.5 concentrations suggest the
      existence of a high PM2.5 (May-October) and a low PM2.5 (November-April) season.
      PM2.5 magnitudes and temporal trends were very similar across the state during
      high PM2.5 events. In fact, the between-site coefficients of determination (R2)
      for daily PM2.5 measurements were 84-98% for June and July. Additionally, during
      the most pronounced PM2.5 episode, PM2.5 concentrations closely tracked the daily
      maximum 1-hr O3 concentrations. These observations suggest the importance of
      transport and atmospheric chemistry (i.e., secondary formation) to PM2.5 episodes
      in New Jersey. The influence of local sources was observed in diurnal
      concentration profiles and annual average between-site differences. Urban
      wintertime data illustrate that high 1-hr maximum PM2.5 concentrations can occur
      on low 24-hr PM2.5 days.

PMID- 11288307
TI  - Limitations of long-path averaging instruments.
AB  - Long-path averaging instruments measure the average velocity or concentration of
      a substance or substances over an averaging path. These measurements are then
      often used for calculation of the average concentration and mass flow rate of the
      substance. The purpose of this paper is to describe some of the limitations of
      these instruments and to suggest ways in which these limitations can be
      minimized. Two limitations were examined: measuring concentration in a single
      dimension (e.g., ignoring the variation in concentration over the width of the
      sample plane), and deriving an average concentration without considering velocity
      effects. The resultant errors will be application-specific. Estimates of the
      second source of error can be obtained from the covariance of concentration and
      velocity profiles over the path length. Unfortunately, suitable field data were
      not available, and to illustrate the method, estimates of the error were obtained
      for a range of possible concentration and velocity profiles. Errors of 50% or
      greater in the mass flow were incurred for the concentration and velocity
      profiles considered. This error was reduced to a negligible level by segmenting
      the averaging path length. It is recommended that velocity and concentration
      profiles be obtained for a broad range of applications to enable the importance
      of covariance errors to be better assessed.

PMID- 11288308
TI  - Mercury mass balances: a case study of two North Dakota power plants.
AB  - The Energy & Environmental Research Center (EERC) conducted a mercury-sampling
      program to provide data on the quantity and forms of Hg emitted and on the Hg
      removal efficiency of the existing air pollution control devices at two North
      Dakota power plants--Milton R. Young Station and Coal Creek Station. Minnkota
      Power Cooperative, Great River Energy, the North Dakota Industrial Commission,
      and EPRI funded the project. The primary objective was to obtain accurate
      measurements of Hg released from each plant, as verified by a material balance. A
      secondary objective was to evaluate the ability of a mercury continuous emission
      monitor (CEM) to measure total Hg at the stack. At both plants, speciated Hg
      measurements were made at the inlets and outlets of both the electrostatic
      precipitators (ESPs) and the flue gas desulfurization (FGD) systems. A Semtech Hg
      2000 (Semtech Metallurgy AB) mercury CEM was used to measure the total Hg
      emissions at the stack in real time. Using these measurements and plant data, the
      measured Hg concentrations in the coal, FGD slurries, and ESP ash, a Hg mass flow
      rate was calculated at each sampling location. Excellent Hg mass balances were
      obtained (+/- 15%). It was also found that the Hg was mostly in the elemental
      phase (approximately 90%), and the small amount of oxidized Hg that was generated
      was removed by the FGD systems. Insignificant amounts of particulate-bound Hg
      were measured at both plants. However, 10-20% of the elemental Hg measured prior
      to the ESP was converted to oxidized Hg across the ESP. The data show that, at
      these facilities, almost all of the Hg generated is being emitted into the
      atmosphere as elemental Hg. Local or regional deposition of the Hg emitted from
      these plants is not a concern. However, the Hg does become part of the global Hg
      burden in the atmosphere. Also, the evidence appears to indicate that elemental
      Hg is more difficult to remove from flue gas than oxidized Hg is.

PMID- 11288309
TI  - Development and preliminary evaluation of a particulate matter emission factor
      model for European motor vehicles.
AB  - Although modeling of gaseous emissions from motor vehicles is now quite advanced,
      prediction of particulate emissions is still at an unsophisticated stage.
      Emission factors for gasoline vehicles are not reliably available, since gasoline
      vehicles are not included in the European Union (EU) emission test procedure.
      Regarding diesel vehicles, emission factors are available for different driving
      cycles but give little information about change of emissions with speed or engine
      load. We have developed size-specific speed-dependent emission factors for
      gasoline and diesel vehicles. Other vehicle-generated emission factors are also
      considered and the empirical equation for re-entrained road dust is modified to
      include humidity effects. A methodology is proposed to calculate modal
      (accelerating, cruising, or idling) emission factors. The emission factors cover
      particle size ranges up to 10 microns, either from published data or from user
      defined size distributions. A particulate matter emission factor model (PMFAC),
      which incorporates virtually all the available information on particulate
      emissions for European motor vehicles, has been developed. PMFAC calculates the
      emission factors for five particle size ranges [i.e., total suspended
      particulates (TSP), PM10, PM5, PM2.5, and PM1] from both vehicle exhaust and
      nonexhaust emissions, such as tire wear, brake wear, and re-entrained road dust.
      The model can be used for an unlimited number of roads and lanes, and to
      calculate emission factors near an intersection in user-defined elements of the
      lane. PMFAC can be used for a variety of fleet structures. Hot emission factors
      at the user-defined speed can be calculated for individual vehicles, along with
      relative cold-to-hot emission factors. The model accounts for the proportions of
      distance driven with cold engines as a function of ambient temperature and road
      type (i.e., urban, rural, or motorway). A preliminary evaluation of PMFAC with an
      available dispersion model to predict the airborne concentration in the urban
      environment is presented. The trial was on the A6 trunk road where it passes
      through Loughborough, a medium-size town in the English East Midlands. This
      evaluation for TSP and PM10 was carried out for a range of traffic fleet
      compositions, speeds, and meteorological conditions. Given the limited basis of
      the evaluation, encouraging agreement was shown between predicted and measured
      concentrations.

PMID- 11288310
TI  - The fate of hydrogen peroxide as an oxygen source for bioremediation activities
      within saturated aquifer systems.
AB  - In situ bioremediation is an innovative technique for the remediation of
      contaminated aquifers that involves the use of microorganisms to remediate soils
      and groundwaters polluted by hazardous substances. During its application, this
      process may require the addition of nutrients and/or electron acceptors to
      stimulate appropriate biological activity. Hydrogen peroxide has been commonly
      used as an oxygen source because of the limited concentrations of oxygen that can
      be transferred into the groundwater using above-ground aeration followed by
      reinjection of the oxygenated groundwater into the aquifer or subsurface air
      sparging of the aquifer. Because of several potential interactions of H2O2 with
      various aquifer material constituents, its decomposition may be too rapid, making
      effective introduction of the H2O2 into targeted treatment zones extremely
      difficult and costly. Therefore, a bench-scale study was conducted to determine
      the fate of H2O2 within subsurface aquifer environments. The purpose of this
      investigation was to identify those aquifer constituents, both biotic and
      abiotic, that are most active in controlling the fate of H2O2. The decomposition
      rates of H2O2 were determined using both equilibrated water samples and soil
      slurries. Results showed H2O2 decomposition to be effected by several commonly
      found inorganic soil components; however, biologically mediated catalytic
      reactions were determined to be the most substantial.

PMID- 11288311
TI  - Forecasting air pollution potential: a synoptic climatological approach.
AB  - This paper describes the development and application of an air pollution
      potential (APP) forecast model based on a synoptic climatological approach in a
      heavily industrialized area in Durban, South Africa. The aim of the forecasting
      procedure, based on a system of orange, red, and all-clear alerts, was to give
      industry advance warning of periods of poor atmospheric dispersion so that it
      could take action to reduce emissions. The key meteorological parameter in
      accurately identifying the commencement of an APP episode was found to be
      negative surface pressure tendency. Wind direction was the most useful parameter
      in estimating the end point of an APP episode. The model was very successful in
      identifying periods of elevated SO2, but there is a need for further refinement
      in forecasting the end point of an episode.

PMID- 11288312
TI  - Weekday/weekend differences in OH reactivity with VOCs and CO in Baltimore,
      Maryland.
AB  - This study compared the first-order frequencies for OH associated with volatile
      organic compounds (VOCs) and CO (hereafter called OH reactivity with VOCs or CO),
      the product of the VOC or CO concentration, and their respective kOH value, on an
      average weekday with that on an average weekend day at a core urban site in
      Baltimore, MD. The average daytime concentrations were calculated for each of the
      55 available Photochemical Assessment Monitoring Station (PAMS) VOCs using data
      from the Baltimore site. The data were sorted in descending order to highlight
      the important species based on concentration. The OH reactivity with VOCs was
      sorted in descending order to identify the important species based on the
      magnitude of the OH reactivity. A similar process was followed for the OH
      reactivity with CO. The contribution of the significant species to the
      weekday/weekend difference in OH reactivity was examined. The OH reactivity with
      C5H8 was the largest among the OH reactivity with the PAMS' VOCs and was the same
      on the weekday and weekend. The weekday/weekend difference in OH reactivity with
      VOCs was entirely due to differences in concentrations of the anthropogenic VOCs.
      The OH reactivity with VOCs was 11% larger on the weekday. When OH reactivity
      with CO was included, the OH reactivity was 13% larger on the weekday.

PMID- 11288313
TI  - In situ monitoring of the mutagenic effects of the gaseous emissions of a solid
      waste incinerator in metropolitan Sao Paulo, Brazil, using the Tradescantia
      stamen-hair assay.
AB  - The present work was designed to determine the potential genotoxicity at the
      vicinity of a solid waste incinerator in the metropolitan area of Sao Paulo,
      using the Tradescantia stamen-hair bioassay. Experiments were carried out between
      December 1998 and April 1999 in four regions (40 pots of plants per site)
      selected on the basis of their pollution levels predicted by theoretical modeling
      of the dispersion of the incinerator's plume. The exposure sites were defined as
      follows: highest level (incinerator); a high level (museum) located 1.5 km from
      the emission point; a moderate level (school, at a distance of 3.5 km from the
      incinerator); and a control (at Jaguariuna countryside). The difference in
      genotoxicity among the groups was statistically significant (p < 0.001). The
      frequency of mutations observed in the countryside was significantly lower [2.25
      +/- 1.55, mean +/- SD (standard deviation)] than that of the sites close to the
      incinerator. The frequency of mutations measured at the school (3.70 +/- 1.36)
      was significantly lower than that measured at both the museum (4.89 +/- 1.12) and
      the incinerator (5.69 +/- 1.34). In conclusion, we found a positive correlation
      between the spatial distribution of the emissions of the incinerator located in
      an urban area and the mutagenic events measured by the Tradescantia stamen-hair
      assay. The in situ approach employed in this study was simple, efficient, and of
      low cost. No air or chemical extraction of pollutants was necessary for
      genotoxicity testing as required by other assays.

PMID- 11288314
TI  - Contribution of LPG-derived emissions to air pollution in the metropolitan area
      of Guadalajara City.
AB  - Measurements of hydrocarbon (HC) emissions generated by the use of liquefied
      petroleum gas (LPG) in the metropolitan area of Guadalajara City (MAG) are
      presented in this work. Based on measurements in the course of distribution,
      handling, and consumption, an estimated 4407 tons/yr are released into the
      atmosphere. The three most important contributors to LPG emissions were refilling
      of LPG-fueled vehicles and commercial and domestic consumption. The MAG shows a
      different contribution pattern of LPG emission sources compared with that of the
      metropolitan area of Mexico City (MAMC). These results show that each megacity
      has different sources of emissions, which provides more accurate strategies in
      the handling procedures for LPG to decrease the impact in O3 levels. This work
      represents the first evaluation performed in Guadalajara City, based on current
      measurements, of the LPG contribution to polluting emissions.

PMID- 11288316
TI  - [Good nutrition in support of therapy].

PMID- 11288315
TI  - [From passive patient to partner in therapy].

PMID- 11288317
TI  - [HIV and AIDS in the aged].

PMID- 11288318
TI  - [Children and adolescents with AIDS].

PMID- 11288319
TI  - [At the source of international aid].

PMID- 11288320
TI  - Common supraventricular tachycardias: mechanisms and management.
AB  - Supraventricular tachycardias (SVTs) are common. Reentry is the most common of
      the underlying mechanisms. The most frequently observed narrow QRS complex SVTs
      are atrioventricular nodal reentrant tachycardia and atrioventricular reentrant
      tachycardia using an accessory pathway. All reentrant tachycardias share certain
      characteristics that distinguish them from automatic or triggered tachycardias.
      These characteristics include unidirectional block, delayed conduction, and
      recovery of excitability within an intact circuit. The characteristics of the
      reentrant circuit and the physiology of the pathways can be used to define
      treatments that may be efficacious and/or may have potential risk.
      Differentiation of SVTs is possible with careful application of monitoring,
      history taking, and electrophysiologic interventions such as programmed
      stimulation.

PMID- 11288321
TI  - A systematic approach to pacemaker assessment.
AB  - Despite the increasing use of pacemaker therapy, assessment of pacemaker function
      and electrocardiogram (ECG) interpretation continue to challenge even experienced
      critical care nurses. Accurate assessment of pacemaker function is essential in
      the evaluation of patients, especially patients with symptoms that may be related
      to pacemaker malfunction such as syncope or palpitations. This article will
      review pacing concepts and pacing system components. A systematic approach to ECG
      interpretation will be presented that can be used in a variety of clinical
      settings.

PMID- 11288322
TI  - Unconventional applications in pacemaker therapy.
AB  - Since its inception, the principal application of permanent pacing has been for
      the correction of symptomatic bradycardia. During the past 3 decades, pacemaker
      therapy indications have evolved, through scientific research and through
      advances in technology, beyond conduction system disorders and sinus node
      dysfunction. This article presents recent progress in the application of
      permanent pacing in hypertrophic obstructive cardiomyopathy, dilated
      cardiomyopathy, paroxysmal atrial fibrillation, neurocardiogenic syncope, and in
      long-QT syndrome. In each clinical entity, certain pacing parameters are crucial
      for achieving the therapeutic goal. Advanced practice clinicians will encounter
      these patients in practice and are urged to recognize the therapeutic goal and
      optimal function of the device.

PMID- 11288323
TI  - Atrial fibrillation: treatment rationale and clinical utility of nonpharmacologic
      therapies.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia
      requiring therapy. Nonpharmacologic therapies for the treatment of AF, namely,
      catheter ablation, cardiac pacing, internal defibrillation, and dysrhythmia
      surgery are playing an increasingly important role in the overall management of
      AF. Although usually prescribed when traditional pharmacologic therapy is not
      effective, not tolerated, or contraindicated, these therapies are rapidly
      assuming a more prominent role as they mature. These modern therapies for AF,
      offering the promise of prevention and cure of AF, potential elimination from the
      sequelae of AF, and significant improvements in quality of life, are increasingly
      becoming more frequent in clinical practice. Further investigation is needed to
      determine which therapy is ideally suited for an individual patient and the
      impact of these varying therapies on morbidity and mortality.

PMID- 11288324
TI  - Living with an implantable cardioverter-defibrillator: a review of the current
      literature related to psychosocial factors.
AB  - Sudden cardiac death (SCD) is responsible for 300,000 deaths annually. Lethal
      ventricular dysrhythmias account for the majority of SCDs. Implantable
      cardioverter-defibrillators (ICDs) are the emerging treatment for lethal
      dysrhythmias. Although reductions in SCD mortality with ICDs are clear, the
      psychologic and social consequences of these devices reveal a mixed success.
      Patients with ICDs have high levels of anxiety and depressive symptoms.
      Conversely, most studies of quality of life in patients with ICDs report that the
      device is well accepted despite fears of being shocked. The ICD shocks are a
      unique aspect of treatment and have the potential to cause psychologic distress.
      Nursing needs to provide care from a holistic perspective. Support groups provide
      reassurance and allow patients to discuss expectations and fears related to the
      ICD. Research needs to be conducted to explore the impact of these devices on the
      lives of patients and their families.

PMID- 11288325
TI  - Implications of gender differences on coronary artery disease risk reduction in
      women.
AB  - Differences in the clinical presentation and resultant treatment of coronary
      artery disease (CAD) for men and women have sensitized advanced practice nurses
      to the importance of addressing gender issues when caring for women with CAD.
      Certain patient characteristics and clinical conditions may place women at higher
      risk of CAD development or progression. These factors include depression, African
      American status, menopausal status, age, type 2 diabetes, and thyroid function.
      In addition, female gender may adversely influence the relative benefits of
      cholesterol lowering in elderly women with borderline high serum cholesterol
      levels and response to interventions for modification of sedentary behavior and
      for smoking cessation. This article addresses emerging knowledge regarding gender
      differences in CAD risk factors and responsiveness to risk reduction
      interventions, issues regarding patient management, the implications of emerging
      knowledge on early detection of CAD risk factors more prevalent in women, and the
      development of targeted intervention approaches.

PMID- 11288326
TI  - Women's risk of decision delay in acute myocardial infarction: implications for
      research and practice.
AB  - Cardiovascular disease is the leading cause of death for women in the United
      States. Despite recent advances in treatment options for acute myocardial
      infarction (AMI), there has not been similar progress in decreasing the time
      between symptom onset and the decision to seek medical help (labeled "decision
      delay") and therefore availability of such treatments. Women delay longer than
      men before seeking help for symptoms of AMI, yet few studies have analyzed
      decision delay by gender. Factors studied to date do not adequately explain the
      differences in decision delay among women or between women and men with AMI.
      Additional research is needed to guide interventions to limit decision delay in
      women at risk for AMI. Until then, clinicians should use existing general
      guidelines to assist women at risk of AMI to avoid decision delay.

PMID- 11288327
TI  - Nutritional and medical therapy for dyslipidemia in patients with cardiovascular
      disease.
AB  - Dyslipidemia is a significant risk factor for the progression of cardiovascular
      disease, particularly when associated with other risk factors. An understanding
      of the pathophysiology and risks for patients with atherosclerotic diseases of
      undertreated dyslipidemia is essential for the healthcare provider. In this
      article, a review of epidemiologic data regarding the role of lipid levels in
      cardiovascular disease prognosis is presented. A familiarity with current dietary
      and drug treatment of lipid disorders is at the core of an evidence-based
      approach to dyslipidemia management in the patient with established
      cardiovascular diseases.

PMID- 11288328
TI  - A multibehavioral intervention to decrease cardiovascular disease risk factors in
      older men.
AB  - The purpose of this study was to compare the effectiveness of two mutibehavioral
      interventions: stress management (SM) (nutrition, exercise, and stress
      management) and education (ED) (nutrition, exercise, and education) on reduction
      of cardiovascular disease (CVD) risk factors in older men. A convenience sample
      (n = 33) of older men (66 +/- 5 years) with at least one CVD risk factor
      participated in this 6-month intervention. Mean receiving the SM intervention (n
      = 25) exercised at the facility twice weekly (at > or = 70% maximum heart rate
      for 40 minutes) and received 12 hours each of nutrition and stress management
      class instruction. Men receiving the ED intervention (n = 8) received the same
      exercise and nutrition protocols but received 12 hours of education without
      stress management. There were no significant differences in body habitus,
      metabolic response, exercise endurance, blood pressure, or heart rate between
      groups at baseline. The SM group had significant pre-post differences in weight,
      body mass index, intraabdominal fat, subcutaneous fat, total cholesterol, low
      density lipoprotein, triglycerides, VO2, supine systolic and diastolic blood
      pressures. The ED group demonstrated significant pre-post differences only in
      supine diastolic blood pressure. There were significant change score differences
      between the groups in triglycerides, subcutaneous fat, VO2, and body mass index.
      Results suggest that a 6-month multibehavioral intervention with stress
      management is effective in decreasing CVD risk factors in older men.

PMID- 11288329
TI  - The use of low-molecular-weight heparin in acute coronary syndromes.
AB  - The initiating event in unstable angina (USA) and non-Q-wave myocardial
      infarction (NQMI) is the rupture of an atherosclerotic plaque resulting in local
      thrombosis. The current standard treatment is the administration of aspirin and
      heparin. The introduction of low-molecular-weight heparin (LMWH) offers a
      potential alternative therapy. Clinical trials have begun to examine the efficacy
      and safety of using LMWH in the management of acute coronary syndromes. Two
      pivotal studies have evaluated the effects of LMWH preparations on patients with
      USA or NQMI: The ESSENCE and the TIMI 11B trials. These studies suggest that LMWH
      plus aspirin is more effective and safer than unfractionated heparin in
      preventing myocardial infarction, recurrent angina, or death. Because of these
      differences, the American College of Cardiology and the American Heart
      Association have updated their guidelines for the treatment of USA and NQMI.

PMID- 11288330
TI  - The way to the heart is all in the wrist: transradial catheterization and
      interventions.
AB  - Currently, the transradial approach to cardiac catheterization and interventions
      is becoming a more popular method of access in the United States. Although the
      radial access site is not new (the approach dates back to the 1940s), it has only
      in the last few years become more widespread. This article provides the expert
      and advanced practice nurse with an understanding of the transradial approach to
      catheterization and percutaneous coronary interventions. The following aspects
      are discussed: the historical perspective, the technique, the nursing care and
      potential complications of the transradial approach, as well as the future
      directions for nursing and medical practice.

PMID- 11288331
TI  - The clinician's approach to evaluating patients with dysrhythmias.
AB  - As cardiac arrhythmia services and the ability to perform electrophysiologic
      testing become more prevalent in the hospital setting, advanced practice nurses
      (APNs) are continually challenged to keep their skills in evaluating patients
      with dysrhythmias sharp and current. The experienced APN evaluates the patient's
      history, recognizes physical findings, and uses noninvasive data to help
      diagnose, anticipate, and even prevent dysrhythmias. This article reviews the
      essential components of a systematic evaluation of patients with a known or
      potential rhythm disturbance.

PMID- 11288332
TI  - Clinical dysrhythmias after surgical repair of congenital heart disease.
AB  - Innovations in surgical and medical treatment continue to improve the outlook for
      children with complex congenital heart disease. Although mortality continues to
      decrease, disease-related morbidity is increasing as a large cohort of these
      patients is reaching young adulthood, pursuing careers, marrying, and in many
      cases having children of their own. Chronic recurrent dysrhythmias are a frequent
      cause of long-term morbidity in this population and result in frequent,
      unanticipated emergency room visits and hospitalizations. Although not usually
      life threatening, they can pose considerable challenges to the patients and the
      providers who care for them. This article provides an overview of the most common
      dysrhythmias encountered in this population, dysrhythmia substrates, and
      therapeutic options.

PMID- 11288333
TI  - [The state of health of the French population in the year 2000].

PMID- 11288334
TI  - [Nursing staff at the "hospital without walls"].

PMID- 11288335
TI  - [Pain, an everyday occurrence in general pediatric nursing services].

PMID- 11288336
TI  - [Evaluation of pain in infants and children].

PMID- 11288337
TI  - [The use of a mixture of an equimolecular mixture of oxygen protoxide of nitrogen
      in pediatrics].

PMID- 11288338
TI  - [Relaxation and hypnosis for pain in children].

PMID- 11288339
TI  - [A unique establishment for blood transfusion in France].

PMID- 11288340
TI  - [Autologous blood transfusion].

PMID- 11288341
TI  - [Maternet: a nursing network within the framework of telemedicine].

PMID- 11288342
TI  - [Stomies: what kind of help to offer the patient?].

PMID- 11288343
TI  - [Semiology of delirium and the role of the nurse].

PMID- 11288344
TI  - [Clinical treatment of paranoia].

PMID- 11288345
TI  - [Therapeutic approach to the patient with delirium].

PMID- 11288346
TI  - [A delicious enigma].

PMID- 11288347
TI  - [The meaning of delirium].

PMID- 11288348
TI  - [Feet and hands tied to the cigarette--3].

PMID- 11288349
TI  - [The seven capital sins in psychiatry].

PMID- 11288350
TI  - [Justice and psychiatry: the role of the expert].

PMID- 11288351
TI  - [The hard and the soft].

PMID- 11288352
TI  - [Assisting the handicapped child and his family].

PMID- 11288353
TI  - [The day care center and the handicapped child].

PMID- 11288354
TI  - [Taking care of the child with movement disorders].

PMID- 11288355
TI  - [The pediatric nurse at the center of medico-social action].

PMID- 11288356
TI  - [Dispensation of drugs to hospitalized children].

PMID- 11288357
TI  - [The resource center for brain-damaged children].

PMID- 11288358
TI  - [The child and competitive sports].

PMID- 11288359
TI  - [Culture and traditions in India].

PMID- 11288360
TI  - [A new international classification of handicaps].

PMID- 11288361
TI  - [Informing parents about the disabilities of their newborn children].

PMID- 11288366
TI  - Introduction to the technical series: what is science, and how does it help us?

PMID- 11288367
TI  - Couple dynamics of change-resistant smoking: toward a family consultation model.
AB  - Smoking is North America's leading cause of preventable morbidity and mortality.
      Although effective cessation treatments exist, their overall effect is modest,
      and they rarely reach the high-risk, health-compromised smokers who need them
      most. Surprisingly, despite evidence that marital relationship variables predict
      the success of cessation efforts, family systems ideas have had little impact on
      current intervention research. We review and critique the cessation literature
      from a systemic viewpoint, illustrate two couple-interaction patterns relevant to
      the maintenance of high-risk smoking, and outline a family-consultation (FAMCON)
      intervention for couples in which at least one partner continues to smoke despite
      having heart or lung disease. Taking into account ironic processes and symptom
      system fit, FAMCON focuses on the immediate social context of smoking, aiming to
      interrupt well-intentioned "solutions" that ironically feed back to keep smoking
      going, and to help clients realign important relationships in ways not organized
      around tobacco usage. Currently in its pilot-testing phase, FAMCON is an
      adjunctive, complementary approach designed to include collaboration with primary
      care physicians and to make smokers more amenable to other, evidence-based
      cessation strategies.

PMID- 11288368
TI  - Chronic illness: trauma, language, and writing: breaking the silence.
AB  - In our work with families that struggle with a chronic illness, we have relied on
      three ideas. First, we regard illness as a relationally traumatizing experience,
      not just for the person with the illness, but for other members of the family as
      well. We use the phrase "relational trauma" because of its effects on members of
      a wider system who also show signs of physical stress, isolation, and
      helplessness (Sheinberg & Fraenkel, 2000). Our second concern is how the
      conversation that leads to new stories is expanded through the development of
      voice and the use of writing. Looking at language, we are particularly attentive
      to the social prevalence of negative metaphors that surround and engulf the ill
      person and her family: dependence, poor genes, repressed personalities, weak
      constitutions, et cetera (Sontag, 1984). These negative metaphors, or outside
      voices, join with the inner voices of the ill person and result in a silence that
      disconnects people at a time when connections must be relied on and above
      question. Our third emphasis is on the use of writing as the means to create new
      voices, metaphors, and multiple descriptions that can reinvigorate the
      conversations silenced by the illness. Once the family's voices are reconstituted
      through writing, the emotions that have been displaced by the illness are
      restored to their conversation. I have included new research from JAMA detailing
      the treatment of patients with chronic illness through their use of writing.

PMID- 11288369
TI  - Family transactions and relapse in bipolar disorder.
AB  - This study examined whether patient symptoms and relatives' affective behavior,
      when expressed during directly observed family interactions, are associated with
      the short-term course of bipolar disorder. Twenty-seven bipolar patients and
      their relatives participated in two 10-minute family interactions when patients
      were discharged after a manic episode. Results indicated that patients who showed
      high levels of odd and grandiose thinking during the interactions were more
      likely to relapse during a 9-month followup period than patients who did not show
      these symptoms during the family discussions. Relapse was also associated with
      high rates of harshly critical and directly supportive statements by relatives.
      Patients' odd thinking and relatives' harsh criticism were significantly more
      likely to be correlated when patients relapsed (r = .53) than when they did not
      relapse (r = .12). Results suggest that bipolar patients who show increased signs
      of residual symptomatology during family transactions during the post-hospital
      period are at increased relapse risk. The data also suggest that relatives of
      relapsing patients cope with these symptoms by increasing both positive and
      negative affective behaviors. Moreover, a bidirectional, interactional
      relationship between patients' symptoms and relatives' coping style seems to
      capture best the role of the family in predicting relapse in bipolar disorder.

PMID- 11288370
TI  - Helping parents deal with children's acute disciplinary problems without
      escalation: the principle of nonviolent resistance.
AB  - There are two kinds of escalation between parents and children with acute
      discipline problems: (a) complementary escalation, in which parental giving-in
      leads to a progressive increase in the child's demands, and (b) reciprocal
      escalation, in which hostility begets hostility. Extant programs for helping
      parents deal with children with such problems focus mainly on one kind of
      escalation to the neglect of the other. The systematic use of Gandhi's principle
      of "nonviolent resistance" allows for a parental attitude that counters both
      kinds of escalation. An intervention is described, which allows parents to put
      this principle into practice.

PMID- 11288371
TI  - A study of the differential effects of Tomm's questioning styles on therapeutic
      alliance.
AB  - To replicate and extend Dozier's (1992) test of Tomm's hypothesis about the
      differential effects of questioning styles on therapeutic alliance, an analogue
      study was conducted. Twenty-eight family triads, each including a son and his
      parents, viewed four videotaped, simulated family therapy scenarios in which
      Tomm's four questioning styles were separately portrayed. Participants were asked
      to identify with the client whose role corresponded to theirs (that is, father,
      mother, or son) and, on the basis of this, to rate the client's alliance with the
      therapist. They were also asked to rate the overall alliance between the family
      and the therapist. Finally, having viewed all four scenarios, they were invited
      to rate comparatively the quality of the therapeutic alliance across the four
      questioning styles. Compared with strategic and lineal questioning styles,
      circular and reflexive questions led to higher ratings of therapeutic alliance on
      all three measures. The results of this study support Tomm's hypothesis that
      questioning styles based on circular assumptions lead to a better therapeutic
      alliance at an individual and systemic level than do questions based on lineal
      assumptions.

PMID- 11288372
TI  - The self-characterization as a narrative tool: applications in therapy with
      individuals and families.
AB  - In this article, I argue that the use of Kelly's self-characterization can aid
      story telling in therapy. It describes the use of the tool's original
      instructions, and of two other versions (the ideal self in 5 years time and the
      family characterization sketch), with individuals and families. In contrast to
      Kelly's practice, clients' written self-descriptions are not stripped to uncover
      cognitive schemata, but are treated as whole narratives. The texts are
      collaboratively analyzed, by looking at both their form and content. The cases
      presented illustrate ways in which these narratives can be read to help
      therapists recognize a person's/family's language "codes" and transgenerational
      family themes. "Warded off areas of feeling" are opened up, and differentiation
      from dominant family voices is facilitated. The whole technique process reveals
      the great importance people place on negotiating, editing, and finally presenting
      a narrative that portrays the way the self and the family are experienced at that
      particular time (see Endnotes).

PMID- 11288373
TI  - Engaging refugee families in therapy: exploring the benefits of including
      referring professionals in first family interviews.
AB  - The possible benefits of including referring professionals in the first family
      interviews are being explored as a way to engage refugee families in therapy.
      Families in exile confront a number of problems related both to premigration
      traumatic exposures and to present adaptation processes. Refugee clients and the
      referring professionals in the larger system frequently see the problems and
      their solutions quite differently. This situation may often result in unclear
      working alliances in a context of therapy. We will describe first family
      interviews in which referring professionals are interviewed about their reasons
      for referrals, and where the families are invited to discuss these
      considerations. The conversations permit families, referrers, and therapists to
      reflect upon differences in positions and perspectives. Their experiences suggest
      that agreements or contracts based on these joint interviews are less ambiguous
      and more clearly formulated than contracts based on interviews with families
      alone. Finally, these experiences are discussed as a potentially valuable
      approach in a cross-cultural context.

PMID- 11288374
TI  - [Structure, localization and physiologic role of pituitary adenylate cyclase
      activating polypeptide (PACAP)].
AB  - PACAP was isolated on the basis of its ability to stimulate adenylate cyclase in
      primary anterior pituitary cell culture from ovine hypothalami by Miyata et al.
      in 1989. This peptide is structurally related to the secretin family and shows a
      67% sequence homology with vasoactive intestinal polypeptide (VIP). The amino
      acid sequence of PACAP has been highly preserved during the evolution that may be
      connected with its important physiological role. Similar to other "brain-gut
      peptides" PACAP is localized not only in the central but in the peripheral
      nervous system and in non-neural tissues as well. In addition to its
      hypophysiotropic effects in the hypothalamo-hypophysial system PACAP exerts its
      effects on water-salt balance, cardiovascular functions, gastrointestinal
      motility and secretion and also on the regulation of reproductive functions.
      PACAP has a role in certain neuro-immuno-endocrine processes, in the
      differentiation of the nervous system, and it has neuroprotective effects in the
      case of ischaemia and various toxic agents. Locally PACAP takes its effects as an
      auto- and paracrine hormone, a neurotransmitter or a neuromodulator in different
      organs. Besides VIP, PACAP plays an important role in the function of the photo
      neuro-endocrine system.

PMID- 11288375
TI  - [Correlation between cancer mortality and alcohol-related mortality in a South
      Hungarian village].
AB  - The author, who had former practical experience in the research-field of the
      medical statistics and alcohol-epidemiology, has collected the data of the total,
      and the cause-specific mortality continuously in the village where he has worked
      as the single GP from December 1986 to 1999. The village is located in the Great
      Hungarian Plain. It is an agricultural community, currently with population of
      2042 inhabitants. The longevity in the village was above the national average.
      Total mortality and cause specific mortality in the village were calculated
      between January 1, 1987 and December 31, 1999. During the period, 503 people
      died. From these 278 (55.3%) were male, and 225 (44.7%) were female. 118 deaths,
      23.5% of all deaths in the village were cancer-related. 67.7% (80 cases) of these
      were among males, and 32.3% (38 cases) among females. 40.7% (48 cases) of cancer
      related deaths were attributable to gastrointestinal-tract cancers (ICD 10 C15
      C26). The proportion of deaths which were directly or indirectly alcohol-related
      was 35.8% (180 cases) of the total mortality. In 50% (90 causes) of these deaths,
      the cause of death was one of the "especially characteristic death's cause of
      alcoholics". Proportion of alcohol-related-mortality attributable to cancer
      related causes was high as 23.9% (43 cases); and vice versa: proportion of cancer
      mortality attributable to alcohol-related causes was 36.4% (50% among males, and
      only 7.9% among females). Cancers of the cavity of mouth and pharynx as cause of
      death (6 cases) occurred only among alcohol-addicted males. The most important
      epidemiological conclusion is that the prevention of alcoholism/alcohol abuse is
      one of the most promising way for the prevention of (certain) cancers, too.

PMID- 11288376
TI  - [Follow-up study of bone mineral density in postmenopausal patients with primary
      biliary cirrhosis].
AB  - Osteopenia is a common complication in primary biliary cirrhosis (PBC). In this
      follow-up study the authors investigated the metabolic bone disease in
      postmenopausal PBC patients. 17 Ca and vitamin D supplemented, postmenopausal
      female patients with PBC (stage II-IV, age: 41-84, mean: 52, each AMA M2
      positive, without ascites) were followed-up for an average of 6.3 years. Bone
      mineral density (BMD) was measured yearly by dual energy x-ray absorptiometry
      (XR26, Norland) in lumbar spine (L2-4), femoral neck (FN), and radius BMC by
      single photon absorptiometry. Urinary pyridinoline/creatinine (Pyr/c) and
      deoxypyridinoline/creatinine ratio (D-Pyr/c) by HPLC, 25-OH-D3 level and standard
      liver function tests were monitored in all patients. At the beginning the BMD was
      decreased in 7 out of 17 patients (T-score < -2.5). The mean BMD was 0.885 SD +/-
      0.26 g/cm2 in L2-4, 0.725 +/- 0.16 g/cm2 in FN and the BMC 0.703 +/- 0.14 g/cm in
      the radius. During follow-up the rate of annual bone loss was increased in
      patients with osteoporosis at the start of this study. There was a correlation
      between the urinary Pyr/c and D-pyr/c values and the annual rate of bone loss in
      patients with PBC (r: -0.79; p < 0.01). In patients with severe osteoporosis at
      the time of the diagnosis of PBC a more pronounced progression of bone loss was
      observed during the follow-up period.

PMID- 11288377
TI  - [Determination of cagA, vacA genotypes of Helicobacter pylori with real-time PCR
      method].
AB  - Presence of cagA gene of Helicobacter pylori (H. pylori) increases proliferation
      of stomach mucosa and it is an index of raised virulence of the bacteria. The
      vacA gene of H. pylori induces a serious inflammation of stomach. The purpose of
      this study was to determine cagA and vacA genotypes of H. pylori using real-time
      polymerase chain reaction (PCR) method with the double strain DNA-(dsDNA) binding
      SYBR Green I. dye. Results were compared with those of two immunohistochemical
      methods. 43 patients' paraffin embedded biopsy tissue samples were examined by
      histology, epidermal growth factor receptor (EGFR), proliferating cell nuclear
      antigen (PCNA) immunohistochemistry and melting curve analysis of real-time PCR
      using LightCycler instrument. Results of histology and real-time PCR from gastric
      biopsies correlated in 57% of cag acases and in 58% of vac cases. Significant
      difference was detected between normal and gastritis cases in the presence of
      cagA gene (p = 0.003) and between normal epithelial and intestinal metaplasia
      cases in the presence of vacA gene (p = 0.045) by investigation of association of
      histology and genotype of bacterium. Statistically significant difference (p =
      0.02) was found between increased cell proliferation and the presence of
      gastritis. Significant correlation was found between the presence of cagA gene
      and EGFR expression in intestinal metaplasia cases (p = 0.0418). Results underlie
      the statistics that infection with cagA positive H. pylori strain increases the
      cell proliferation on the stomach mucosa and raises the chance of development of
      intestinal metaplasia. Infection with vacA positive H. pylori inhibits the signal
      transduction pathway of EGFR, which influences mechanisms of mucosa repair. The
      role of EGFR and H. pylori infection is yet unclear in intestinal metaplasia and
      cancer. The authors' method seem to be suitable for determination of genotypes of
      H. pylori.

PMID- 11288378
TI  - [The philantropist executioner].

PMID- 11288379
TI  - [Antal Marek (1903-1983), medical writer of North-Hungary].

PMID- 11288380
TI  - [Introducing the Kalman Pandy Hospital and Outpatient Clinic of Bekes County
      Local Government].

PMID- 11288381
TI  - [Regarding N.N.Korotkov, Russian surgeon].

PMID- 11288382
TI  - [Let's learn the Hungarian medical literature].

PMID- 11288383
TI  - Hypertension clinical guideline 2000.
AB  - OUTCOMES: Extensive data from many randomised controlled trials have shown the
      benefit of treating hypertension. The target blood pressure (BP) for
      antihypertensive management should be systolic < 140 mmHg and diastolic < 90
      mmHg, with minimal or no drug side-effects. However, a lesser reduction will
      elicit benefit, although this is not optimal. The reduction of BP in the elderly
      and in those with severe hypertension should be achieved gradually over 6 months.
      Stricter BP control is required for patients with end-organ damage, coexisting
      risk factors and co-morbidity, e.g. diabetes mellitus. Coexistent risk factors
      should also be controlled. BENEFITS: Reduction in risk of stroke, cardiac
      failure, renal insufficiency and probably coronary artery disease. The major
      precautions and contraindications to each antihypertensive drug recommended are
      listed. RECOMMENDATIONS: Correct BP measurement procedure is described.
      Evaluation of cardiovascular risk factors and recommendations for
      antihypertensive therapy are stipulated. The total cardiovascular disease risk
      profile should be determined for all patients and this should inform management
      strategies. Lifestyle modification and patient education play an essential role
      in the management strategy. DRUG THERAPY: First line--low-dose diuretics; second
      line--add one of the following: reserpine, beta-blockers, angiotensin-converting
      enzyme (ACE) inhibitors or calcium channel blockers; third line--add another
      second-line drug or hydralazine or an alpha-blocker. The guideline includes
      management of specific situations, e.g. hypertensive emergency or urgency, severe
      hypertension with target organ damage and refractory hypertension (BP > 160/95
      mmHg on triple therapy), hypertension in diabetes mellitus, etc. VALIDATION: The
      guideline was developed by the Executive Committee of the Southern African
      Hypertension Society with consensus meeting endorsement, and is endorsed by the
      South African Medical Association Guideline Commitee.

PMID- 11288384
TI  - Remaking the Cape's financial bed.

PMID- 11288385
TI  - GlaxoSmithKline: another pharmaceutical giant E-merge-S.

PMID- 11288386
TI  - Broncho-oesophageal fistula due to idiopathic oesophageal ulceration in a patient
      with AIDS.

PMID- 11288387
TI  - Motor vehicle accidents in the Namib Desert, Namibia.

PMID- 11288388
TI  - Pre-operative assessment of the lung cancer patient.

PMID- 11288389
TI  - Confidentiality--a dying wish?

PMID- 11288390
TI  - Memorable deliveries.

PMID- 11288391
TI  - Recommendations pertaining to the use of viral vaccines: influenza. Review of
      influenza activity--2000.

PMID- 11288392
TI  - When is it not Huntington's disease?

PMID- 11288393
TI  - Necrotising enterocolitis as an infectious disease--evidence from an outbreak of
      invasive disease due to extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae.

PMID- 11288394
TI  - Childhood acute viral hepatitis in Cape Town.

PMID- 11288395
TI  - Evaluating the clinical management of severely malnourished children--a study of
      two rural district hospitals.
AB  - BACKGROUND: Severe malnutrition is an important cause of preventable mortality in
      most South African hospitals. Work recently done in two rural Eastern Cape
      hospitals supports the literature which shows that many deaths occur as a result
      of outdated clinical practices and that improving these practices reduces case
      fatality rates. Rapid assessment of clinical management in paediatric wards is
      necessary to highlight areas for improvement. OBJECTIVE: To assess the management
      of severely malnourished children in two rural district hospitals and to
      recommend improvements for their care. METHODS: Based on draft World Health
      Organisation (WHO) guidelines for inpatient care of children with severe
      malnutrition, data collection instruments were developed in conjunction with the
      district nutrition team to assess the quality of care given to malnourished
      children in two Mount Frere hospitals, Eastern Cape. Data were collected through
      retrospective review of case records, with detailed studies of selected cases,
      structured observations of the paediatric wards, and interviews with ward sisters
      and doctors. RESULTS: The combined case fatality rate for severe malnutrition was
      32%. Inadequate feeding, poor management of rehydration and infection, lack of
      resources, and a lack of knowledge and motivation among staff were identified as
      areas that need attention. CONCLUSION: The clinical management of severely
      malnourished children can be rapidly assessed to highlight areas for improvement.
      Involving staff in the assessment process has led to their active involvement in
      improving the management of malnourished children in their hospitals.

PMID- 11288396
TI  - Craniocerebral gunshot injuries in South Africa--a suggested management strategy.
AB  - OBJECTIVE: To determine the outcome of craniocerebral gunshot injuries, analyse
      factors that affect prognosis and suggest a management protocol. DESIGN: A
      retrospective analysis of civilian craniocerebral gunshot injuries treated over a
      7-year period. SETTING: Groote Schuur Hospital's neurosurgery and trauma unit
      service. PATIENTS: One hundred and eighty-one patients with craniocerebral
      gunshot injuries were admitted to the Department of Neurosurgery, Groote Schuur
      Hospital, University of Cape Town, over a 7-year period and a retrospective
      analysis of these patient records with regard to outcome and prognostic factors
      was carried out. RESULTS: Seventy-six patients sustained non-penetrating
      injuries, 8 (11%) of whom had underlying cerebral injury on computed tomography
      (CT) scan. The prognosis was good in the case of non-penetrating injuries. One
      hundred and five patients sustained penetrating injuries and 57% (62) had a poor
      outcome. A Glasgow Coma Score (GCS) of 5 or less following resuscitation was
      associated with a 98% mortality rate. CT scan evidence of transventricular injury
      was associated with 100% mortality, bihemispheric injury with 90% mortality, and
      diffuse cerebral swelling with 81% mortality. CONCLUSION: Patients with non
      penetrating craniocerebral gunshot injuries should all undergo a CT scan as 10%
      will have cerebral injury. The prognosis is normally good. In penetrating
      craniocerebral gunshot injuries a GCS of 5 or less, or a GCS of 8 or less with CT
      scan findings of transventricular or bihemispheric injury have such a poor
      outcome that conservative treatment is indicated.

PMID- 11288397
TI  - Intoxication, criminal offences and suicide attempts in a group of South African
      problem drinkers.
AB  - BACKGROUND: Incidence rates of crime and alcohol abuse in South Africa are
      unacceptably high. Research suggests a relationship between alcohol and both
      crime and suicide. This study aims to add to the information base on this topic
      in South Africa. METHODS: This is a cross-sectional record study of criminal
      offences and suicide attempts in 269 admissions to an alcohol rehabilitation unit
      in the Western Cape. Types of criminal offences and suicide attempts are
      described. Relationships are sought between crime, violent crime and suicide
      attempts on the one hand, and demographic and alcohol-related variables on the
      other. RESULTS: One hundred and four subjects (39%) had criminal convictions, the
      majority of which were committed while the subjects were intoxicated. The
      commonest alcohol-related crimes were driving-related (17% of subjects) and
      crimes of violence (15%). Male gender, younger age at initiation of drinking, and
      earlier onset of problem drinking were significantly associated with criminal
      behaviour. Violent crime was associated with earlier onset of initial, regular
      and problem drinking, and maternal alcohol abuse. Suicide attempts (24% of
      subjects) were associated with female gender, white racial group, not being in a
      marital relationship, younger current age and early age of problem drinking.
      CONCLUSIONS: There was an association between intoxication and both violent crime
      and suicide attempts. The importance of population studies and the need for
      intervention programmes aimed at teenagers who are drinking, are emphasised.

PMID- 11288398
TI  - STD care in the South African private health sector.
AB  - OBJECTIVES: To establish the accessibility and quality of sexually transmitted
      disease (STD) care provided by private general practitioners (GPs) and workplace
      health services in South Africa. DESIGN: Structured telephone interviews were
      conducted with a random national sample of 120 GPs and 244 occupational health
      nurses (OHNs) between May and July 1997. The interview schedules covered
      indicators of access (including utilisation) and processes (drug treatment,
      partner management, counselling and condom promotion) of STD care. RESULTS: An
      estimated 5 million STD-related visits were made to private general practices in
      1997. Reported treatment of STDs was assessed for effectiveness using well
      established syndromic case management guidelines. Only 28% of GPs reported
      effective treatment for urethral discharge. This dropped to 14% for genital ulcer
      and 4% for pelvic inflammatory disease. Fifty-five per cent of the OHNs
      interviewed indicated that their workplace clinics provided STD care. Nurses
      provided this care, with or without the support of doctors, in 87% of clinics.
      Reported urethral discharge and genital ulcer treatment regimens were assessed as
      effective in 34% and 14% of responses, respectively. CONCLUSIONS: The private
      sector is a major provider of STD care and is key to national efforts to achieve
      better STD control, thereby preventing the spread of HIV. However, the results of
      the research suggest that the poor quality of STD care may be undermining
      attempts to control these epidemics in our society. Although a complex task,
      strategies need to be found to improve the quality of care provided within the
      private sector.

PMID- 11288399
TI  - Prevalence of diabetes mellitus and impaired glucose tolerance in factory workers
      from Transkei, South Africa.
AB  - OBJECTIVE: To determine the prevalence of diabetes mellitus and impaired glucose
      tolerance (IGT) in a group of peri-urban black South Africans. DESIGN: Cross
      sectional study in which an oral glucose tolerance test (OGTT) was performed on
      each subject. SETTING: Two of the largest factories in the surroundings of
      Umtata, the capital of the former homeland of Transkei, South Africa. SUBJECTS: A
      total of 374 Xhosa-speaking factory workers. MAIN OUTCOME MEASURES: Frequency of
      diabetes mellitus and IGT according to age group and gender using the current
      World Health Organisation (WHO) criteria for the diagnosis of abnormal glucose
      tolerance and its relationship to obesity. RESULTS: The crude prevalences for
      diabetes mellitus and IGT were 2.45% and 2.7% respectively. The age-adjusted
      prevalences using a standard world population were 4.5% (confidence interval (CI)
      1.54-7.42) and 5.1% (CI 2.45-5.51) for diabetes and IGT respectively. The
      prevalence of diabetes was similar in male and female workers (P = 0.31), with
      the highest incidence observed in the age group from 40 to 59 years. No subject
      below the age of 40 years was found to be diabetic, and the prevalence of the
      disease was found to increase with age. Obesity was present in 22.2% of all
      subjects. Prevalence of obesity was similar in subjects with diabetes and in
      those with impaired and normal glucose tolerance (P = 0.71). However, overweight,
      identified in 26.8% of subjects, was more frequently observed in the IGT group
      than in the other two groups (P = 0.01). IGT was observed in 3.4% of male and
      1.5% of female workers respectively (P = 0.13), with peak prevalences occurring
      between the ages of 30 and 49 years. CONCLUSION: In conclusion, this study found
      a prevalence of diabetes and IGT comparable to prevalence results reported in
      other black South African communities. The implications with regard to this
      community merit further study.

PMID- 11288400
TI  - 'Playing god'?--the dilemmas of neonatal critical care.

PMID- 11288401
TI  - Legalizing advance directives.

PMID- 11288402
TI  - CPD--equal opportunity?

PMID- 11288403
TI  - Rectovaginal fistulas in HIV-infected children.

PMID- 11288404
TI  - What do medical women want?

PMID- 11288405
TI  - Cholera update--management on the ground.

PMID- 11288406
TI  - Doctor burnout silent and fatal.

PMID- 11288408
TI  - [Public health and nursing care in Europe].

PMID- 11288407
TI  - [The patient's first contact: the nurse].

PMID- 11288409
TI  - [Nursing services outside Germany].

PMID- 11288410
TI  - [Connection between nursing and education].

PMID- 11288411
TI  - [The concept of activity training].

PMID- 11288412
TI  - [Positions of ethics].

PMID- 11288413
TI  - Estimating energy expenditure in critically ill adults and children.
AB  - Designing effective nutrition support regimens for critically ill patients
      requires an understanding of the energy needs of each patient. Many disease
      processes result in elevated caloric requirements, whereas some clinical
      procedures and medications may diminish the metabolic response. Experienced
      clinicians are unable to predict the extent to which trauma or injury will affect
      energy requirements for an individual. Both under- and overfeeding a critically
      ill patient may prolong hospitalization and increase morbidity and mortality.
      Applying equations that were originally developed for healthy nonhospitalized
      individuals to predict the energy requirements of critically ill patients will
      often result in significant errors and may lead to provision of inappropriate
      nutritional support. The measurement of resting energy expenditure by indirect
      calorimetry is a valuable tool and can be used to predict energy requirements for
      most spontaneously breathing critically ill patients, but may lead to spurious
      results in mechanically ventilated pediatric patients. In the complex and rapidly
      changing context of critical illness, individualized assessment of energy
      requirements is crucial. Whichever technique is used initially to assess energy
      requirements, sequential monitoring and constant reassessment of each patient is
      essential to provide the appropriate nutritional care regimen. The purpose of
      this article is to review the equations for estimating and the techniques,
      practical aspects, and interpretation of measuring energy expenditure in
      critically ill patients.

PMID- 11288414
TI  - Nutrition assessment of the critically ill child.
AB  - Nutrition assessment is an integral part of the evaluation of the critically ill
      child. The goal of nutrition assessment is to identify those children who are
      malnourished and those who are at risk of becoming malnourished. Malnutrition is
      known to affect wound healing, infection rate, mortality, and morbidity, making
      early identification of children at risk essential. An initial assessment
      consists of a complete history and physical examination. The history and physical
      examination findings are then evaluated in conjunction with appropriate
      laboratory and anthropometric measurements. Through vigilant nutrition
      assessment, prompt, appropriate nutrition support can be provided to the
      critically ill child.

PMID- 11288415
TI  - Delivery of enteral nutrition.
AB  - There is increasing evidence that enteral feeding is superior to parenteral
      nutrition with regard to maintaining gut structure and function. Selection of the
      enteral access route depends on the type and anticipated duration of nutrient
      delivery. At present, enteral feeding devices can be divided into two major
      categories: those entering the gastrointestinal tract through the oral or nasal
      cavity (oroenteric or nasoenteric tubes) and those entering through the abdominal
      wall including gastrostomy, duodenostomy, or jejunostomy tubes. This article
      provides a review of methods to insert and confirm gastric and intestinal feeding
      tube placement. Care of the patient with an enteric tube will be described.

PMID- 11288416
TI  - Bedside placement of postpyloric feeding tubes.
AB  - Postpyloric placement of feeding tubes into the duodenum or jejunum is often
      recommended to support early feeding, improve tolerance of enteral nutrition, and
      decrease the risk of aspiration pneumonia. Achieving small bowel feeding tube
      placement can be a difficult, time-consuming, and costly process that may delay
      the initiation of enteral nutrition. Various bedside techniques, including air
      insufflation, pH assisted, and spontaneous passage with or without motility
      agents are available to facilitate transpyloric feeding tube passage. A
      discussion of these methods is presented in this article, including a hospital
      based quality initiative project designed to facilitate early enteral nutrition.

PMID- 11288417
TI  - Predictors of tube feeding in acute stroke patients with dysphagia.
AB  - Stroke is the third leading cause of death and the leading cause of disability in
      adults. Dysphagia, or difficulty with swallowing, is an untoward outcome of
      stroke occurring in as many as 71% of stroke survivors. This study sought to
      identify characteristics in stroke patients predictive of tube feeding dependency
      during acute care secondary to neurogenic oropharyngeal dysphagia. Significant
      differences in age, stroke severity scores, length of stay, and cost per case
      were measured between the tube feeding and control group patients. Univariate
      analysis identified the existence of seven dependent risk factors, of which four
      were found to be independent risk factors for the outcome of interest: wet voice
      after swallowing water, hypoglossal nerve dysfunction, National Institutes of
      Health Stroke Scale score, and incomplete oral labial closure. Findings from this
      study may assist healthcare providers in the early identification of stroke
      patients at risk for clinically significant neurogenic oropharyngeal dysphagia,
      facilitating reduction of untoward outcomes.

PMID- 11288418
TI  - Nutrition for the critically ill child: enteral and parenteral support.
AB  - The requirements of growth and organ development create a challenge in nutrition
      management for the pediatric patient. The stress of critical illness further
      complicates the delivery of adequate nutrients. Enteral feeding has several
      advantages over parenteral nutrition (PN), which include preservation of the
      gastrointestinal mucosa and decreasing the occurrence of sepsis related to
      bacterial translocation. Although feeding through the gastrointestinal tract is
      the preferred route for nutritional management, there are specific instances when
      PN as adjunctive or sole therapy is necessary to meet nutritional needs. With
      meticulous attention to fluid, caloric, protein, and fat requirements along with
      monitoring the metabolic status of the patient, it is possible to provide full
      nutritional support for the critically ill child within 24 to 48 hours of
      hospital admission.

PMID- 11288419
TI  - Parenteral nutrition for the acutely ill.
AB  - Parenteral nutrition (PN) is one of the most sophisticated forms of intravenous
      therapy in use today. Intravenous feeding is a life-saving technology for
      patients unable to maintain their nutritional status using the gastrointestinal
      tract. Although PN has become an integral component of patient care, the risks
      associated with this therapy must be weighed against the potential benefits.
      Comprehensive clinical management includes selection of candidates,
      implementation and monitoring of therapy, and ensuring a seamless transition when
      PN is no longer required. Optimal parenteral nutrition demands expertise in
      caring for vascular access devices. A collaborative approach to care minimizes
      the risks associated with PN and ensures positive patient outcomes.

PMID- 11288420
TI  - Drug-nutrient interactions: a review.
AB  - Concurrent administration of medications and nutrients can lead to interactions
      that change the absorption or metabolism of the medication or nutrient. Some of
      these interactions have little or no impact on the patient while others may be
      fatal. The objective of this article is to review the mechanisms of various drug
      nutrient interactions. Topics to be discussed include specific populations at
      risk of interactions, nutrients that have a positive and negative effect on drug
      absorption, nutrients that result in alterations of drug metabolism, and a
      variety of pharmacologic interactions of medications with nutrients. It is vital
      that healthcare providers are familiar with drug-nutrient interactions and
      continue to educate themselves and their patients to optimize the effectiveness
      and minimize the toxicities of medications.

PMID- 11288421
TI  - Management of cancer cachexia.
AB  - The diagnosis of cancer has traditionally been associated with malnutrition and
      wasting. Oncology patients are at risk for nutrition-related problems because of
      the cancer itself, as well as the treatment prescribed. Clinical manifestations
      of cachexia include anorexia, weight loss, muscle wasting, and fatigue, resulting
      in poor performance status. Control of symptoms, such as anorexia, nausea and
      vomiting, and mucositis is imperative in the management of cancer cachexia.
      Current pharmacologic therapies, as well as complementary and alternative
      methods, are presented. The nurse plays a key role in ensuring that the
      nutritional needs of oncology patients are met.

PMID- 11288422
TI  - Management of the patient with short bowel syndrome.
AB  - Extensive resection of the small bowel results in impaired digestion of
      macronutrients and malabsorption of nutrients, fluid, electrolytes, and minerals.
      Gastric acid hypersecretion and alterations in gut hormonal response further
      contribute to the problem. Diarrhea, dehydration, electrolyte and acid/base
      abnormalities, and macronutrient and micronutrient deficiencies ensue, and is
      termed the short bowel syndrome (SBS). Rare disorders, such as essential fatty
      acid deficiency and D-lactic acidosis, are a greater concern for the SBS patient.
      These patients' lives are significantly impacted, and they require close
      monitoring by a medical team knowledgeable about the disease and its nutritional,
      metabolic, and psychosocial consequences. Immediate therapies are directed toward
      fluid resuscitation, wound healing, and initiation of early nutrition support.
      After medical stabilization, multiple nutritional and medicinal therapies are
      used to aid bowel adaptation and prevent medical crisis. Advanced practice nurses
      should be knowledgeable about SBS to educate patients and families about this
      disease, associated therapies and changes in lifestyle, and how to detect and
      manage acute changes in medical condition.

PMID- 11288423
TI  - Use of indirect calorimetry to optimize nutrition support and assess physiologic
      dead space in the mechanically ventilated ICU patient: a case study approach.
AB  - Indirect calorimetry (IC) is an accurate method of estimating a patient's energy
      expenditure, particularly the complex critically ill patient who benefits most
      from an individualized regimen of nutritional support. This bedside technique
      measures variables related to gas exchange and replaces assumptions about
      physiologic stress. When indirect calorimetry data are augmented by an arterial
      blood gas analysis of carbon dioxide (PaCO2), the dead space to tidal volume
      ratio (VD/VT) can be determined for an individual patient. These data can be
      valuable to the healthcare team when checking reasons for weaning failure. A case
      study approach to a 69-year-old man with acute respiratory distress syndrome and
      biliary sepsis will demonstrate the utility of this measurement. Attention to
      precise nutritional support and optimal gas exchange can influence the outcome of
      critically ill mechanically ventilated patients. This discussion highlights the
      potential benefits of indirect calorimetry for critical care nurses.

PMID- 11288424
TI  - [The French and their nutrition].

PMID- 11288425
TI  - [Nutrition at work].

PMID- 11288426
TI  - [Oral nutrition supplements for home use].

PMID- 11288427
TI  - [Role of the nurse in cases of malnutrition].

PMID- 11288428
TI  - [The nurse's role in anesthesia].

PMID- 11288429
TI  - [Pharmacokinetics of drugs].

PMID- 11288430
TI  - [Methods of administration: intravenous immunoglobulins].

PMID- 11288431
TI  - [Pain experienced by the patient: the other side of the mirror].

PMID- 11288432
TI  - [Osteogenesis imperfecta: hope in treatment].

PMID- 11288433
TI  - [Childhood diabetes].

PMID- 11288434
TI  - [Psychological aspects of insulin-dependent diabetes].

PMID- 11288435
TI  - [Health education: a public health priority].

PMID- 11288436
TI  - [Individualized acceptance, integration of the diabetic child in school].

PMID- 11288437
TI  - [Education about diabetes, help to young diabetics (AJD)].

PMID- 11288438
TI  - [Histories of diabetes, "Marmelade", the cat].

PMID- 11288439
TI  - [Prevention of backache in schoolchildren].

PMID- 11288440
TI  - [Reflexions on sleep: the ups and downs of sleep].

PMID- 11288442
TI  - [The educational process, from obligation to creativity].

PMID- 11288441
TI  - [Evaluation of nursing care with the purpose of continuous improvement].

PMID- 11288443
TI  - [Measles, mumps, rubella: important health risks].

PMID- 11288444
TI  - [The nurse in clinical research, at the heart of pharmacological innovation].

PMID- 11288445
TI  - [Increasing transfusion safety].

PMID- 11288446
TI  - [Hematologic vigilance].

PMID- 11288447
TI  - [Ambulatory surgery, a new enterprise].

PMID- 11288448
TI  - [Nursing care of ulcers].

PMID- 11288449
TI  - [Diabetes: education of the young child].

PMID- 11288450
TI  - [Everything involving the body].

PMID- 11288451
TI  - [The body, psychoses and phoric function].

PMID- 11288452
TI  - ["As if the feet were thinking"].

PMID- 11288453
TI  - [The body and symbolic equation, symbole and sex].

PMID- 11288454
TI  - [Institutional observation of bodily messages].

PMID- 11288455
TI  - [School centered on the body].

PMID- 11288456
TI  - [Place of the child's body in the school environment].

PMID- 11288457
TI  - [The history of Denis, without papers, dissociated, incarcerated].

PMID- 11288458
TI  - [The fatigue syndrome in nurses and nurses aides (2)].

PMID- 11288459
TI  - [Psychiatric emergency, a shock to be treated].

PMID- 11288460
TI  - [The seven capital sins in psychiatry (2)].

PMID- 11288461
TI  - High incidence of noninfectious esophagitis in orthotopic liver transplant (OLT)
      recipients.
AB  - Incidence of esophagitis among cirrhotics is similar to the general population;
      post-OLT course of this entity is not well known. The aim of this study was to
      assess the incidence of non-infectious esophagitis among OLT recipients. Patients
      with chronic liver disease who have been considered for transplantation have
      undergone esophagogastroduodenoscopy (EGD) for examination of the upper
      gastrointestinal tract. Following transplantation, some of these patients have
      required EGD for various reasons. EGD findings following transplantation were
      compared to that individual's pre-transplant findings. There were 173 patients
      and the median age was 49. The incidence of pre-transplant esophagitis was 7.5%,
      which increased to 22% after OLT (p > 0.0001). None had specific etiology.
      Etiology of this increase needs to be further investigated and the effects of
      immunosuppressive drugs on lower esophageal sprinter and gastric motility should
      be clarified. Use of acid suppressing drugs during the early post-transplant
      period should be considered.

PMID- 11288462
TI  - Equal partners: doctors and patients explore the limits of autonomy.
AB  - In recent decades medicine--like all social institutions--has fallen from public
      trust. Managed care has made third-party payers a partner in the physician
      patient relationship. Advocate groups, some lawyers, and bioethicists have
      encouraged patients to demand a greater voice in medical decisions. Physicians
      and patients are forced to relate to each other in a narrower range, and more of
      the physician's actions are being dictated and standardized. Physicians are often
      seen as a threat to the patient's autonomy and believed to be too paternalistic,
      authoritarian, and too concerned with profit to be reliable partners. A review
      and synthesis of the literature supports the view that patients prefer to have
      decisional control over outcomes but leave technical decisions on how to achieve
      those outcomes to physicians. Good medical care is a process of having one's
      autonomy respected and knowing when to relinquish it. Promoting patient autonomy
      as an ultimate value in medicine rather than recognizing it as one value among
      others (such as caring, trust, and honesty) is an error. The task of medicine is
      not to banish paternalism, but to preserve kindness and respect for the patient
      as a person.

PMID- 11288463
TI  - Oklahoma medicine: tales from territorial days.

PMID- 11288464
TI  - Arthritis: an impending public health epidemic.

PMID- 11288465
TI  - Towards agreement on ways to measure and report drinking patterns and alcohol
      related problems in adult general population surveys: the Skarpo conference
      overview.
AB  - A thematic conference of the Kettil Bruun Society (KBS) for Social and
      Epidemiological Research on Alcohol was held in Skarpo, near Stockholm, on April
      3-7, 2000. The goals of the meeting were to develop consensus sets of
      questionnaire items for measuring alcohol consumption and social harm, to
      delineate statistical and practical concerns related to the aggregation of
      consumption and harm data and to identify summary measures to be used for
      descriptive purposes and in analyses of the association between alcohol intake
      and alcohol-related outcomes. The results of the conference discussions are
      summarized below, with emphasis on both areas where the conference yielded
      recommendations for measures and methods of aggregation for analysis, and on
      areas where consensus could not be obtained and/or where additional research is
      needed.

PMID- 11288466
TI  - Dimensions of alcohol-related social and health consequences in survey research.
AB  - Dimensions of alcohol-related social and health consequences are approached from
      two different perspectives. First, classical approaches with factor analytic
      techniques are used to empirically determine the dimensionality of item batteries
      intended to measure harm. Second, a closer look is taken at theoretically
      underlying dimensions of social and health consequences and their association
      with alcohol consumption. Using as empirical material data from the US national
      survey of males aged 21-59 (N3) conducted in 1969, the following specific
      questions are discussed: (1) What are the underlying dimensions of alcohol
      related social and health consequences? (2) How should the relation between
      alcohol consumption and consequences best be assessed (in terms of
      epidemiological traditions or social constructivist traditions)? (3) How can we
      best incorporate the time perspective into modeling the relationship between
      alcohol consumption and consequences? A first attempt is made to develop
      practical guidelines for future research on handling these problems.

PMID- 11288467
TI  - The role of social and health statistics in measuring harm from alcohol.
AB  - Since excess use of alcohol contributes to so many varieties of health and social
      harms, in most countries, there are many potential sources of data indicative of
      alcohol-related harms. In few instances, compilation and interpretation of these
      data are straightforward, but, mostly, they are open to various sources of
      measurement error, which need to be taken into account if they are to be applied
      for research purposes. Police and health statistics are the major source of such
      information, but the underlying systems are not usually set up with the purpose
      of monitoring alcohol-related events. In both of these domains, types of events
      can be identified, which are wholly attributable to excess alcohol use, i.e.
      drunk-driving, alcoholic liver cirrhosis. Specific alcohol-related events are
      particularly prone to variations in, respectively, police enforcement practices,
      medical diagnostic fashion and sensitivity to prejudices about alcohol-related
      problems. A case will be made in this paper for the use of multiple surrogate
      measures of alcohol-related harm drawn from several sources in order to measure
      and track local, regional and national trends. For health statistics on mortality
      and morbidity, the aetiologic fraction (AF) method will be recommended for such
      monitoring purposes. It will also be recommended that these data be categorised
      by the degree to which cases are attributable to alcohol and also by whether the
      underlying hazardous drinking pattern is a brief drinking bout or a sustained
      pattern of heavy intake over a number of years. Nighttime occurrences of road
      crashes, public violence from both police and emergency room attendance data will
      also be recommended. It will be argued that routine recording of alcohol
      relatedness of events is usually unreliable, and the above surrogate measures are
      preferable. Recommendations will also be made for utilising national surveys of
      drinking behaviour to improve the calculation of alcohol-related morbidity and
      mortality, as well as refine estimates of per capita alcohol consumption, another
      major 'surrogate' measure of alcohol-related harm. The arguments will be
      illustrated with reference to Australia's National Alcohol Indicators Project and
      related research projects.

PMID- 11288468
TI  - Aggregating dimensions of alcohol consumption to predict medical and social
      consequences.
AB  - BACKGROUND: Alcohol consumption has many different dimensions. For each potential
      medical or social outcome, different dimensions of consumption may have different
      relationships. However, these relationships are not independent of each other and
      this multidimensionality is often mishandled or not taken into consideration at
      all in current alcohol epidemiology. OBJECTIVE: To give recommendations on how to
      aggregate dimensions of alcohol consumption to predict social and medical
      consequences. METHODS: Based on a review of relevant papers, different
      statistical methods to deal with aggregating dimensions of alcohol consumption in
      predicting outcomes are compared and discussed. RESULTS: Regression approaches
      may be used to aggregate different dimensions of alcohol consumption to predict
      medical and social outcomes. However, the substantive interpretation of
      regression in general has to be taken into consideration. CONCLUSIONS: Future
      research in alcohol epidemiology should incorporate different dimensions of
      consumption and should analyze them by regression approaches either using the
      dummy variable approach or using suitable interaction terms.

PMID- 11288469
TI  - The measurement of drinking patterns and alcohol problems in Nigeria.
AB  - As in most other societies, alcoholic beverages have been consumed in what is
      present-day Nigeria for a long time. Before the arrival of western factory-made
      drinks, alcohol consumption was limited to a variety of beverages produced from
      palm trees and food grains. Today, beer has become the most popular drink in the
      country but traditional beverages (palm wine, burukutu, ogogoro, pito) are still
      widely consumed in both rural and urban areas. Though research has shown that
      heavy drinking seems to be the norm among those who drink any type of alcohol,
      there is no clear association between drinking and social or health problems. On
      the other hand, certain types of beverages are linked with positive attributes.
      Despite their potential significance, these and other issues have not received
      the attention they deserve in the alcohol research literature on Nigeria and
      other African countries. The focus of this paper is on the need to take into
      consideration relevant measurement issues (e.g., container and serving size,
      alcohol contents, drinking expectancies, perceived risks associated with the
      consumption of different types of alcoholic beverages, as well as reasons for
      drinking) in alcohol research. It is suggested that a better understanding of
      these and related factors is necessary for the advancement of alcohol
      epidemiology in the country.

PMID- 11288470
TI  - The measurement of drinking patterns and consequences in Mexico.
AB  - The paper addresses the experiences of measuring and monitoring patterns of
      alcohol consumption and consequences in Mexico, provides an overview of alcohol
      use and problems, describes local cultural values that influence patterns of
      drinking, and discusses measurement implications.

PMID- 11288471
TI  - The measurement of alcohol-related social problems in Sweden.
AB  - During the first decades following the end of World War II, registers were the
      predominant data source in Sweden for studying alcohol-related problems and,
      before the abolition of the rationing system, also for mapping drinking habits.
      This was possible due to the strict individual control system of alcohol that
      dominated in Sweden for many decades. With the gradual shift from individual
      control to general control in the 1960s, and 1970s, the possibility of using
      registry data was reduced, and for the past 20 years or so they have almost never
      been used to study the relationship between drinking and social problems.
      Instead, not only drinking levels and drinking patterns, but also social problems
      associated with alcohol, have slowly but to an increasing extent been measured by
      self-reported questions in general population surveys. This paper discusses
      experiences gained from working with self-reported survey data on alcohol-related
      social problems in Sweden for the past few years and describes discrepancies
      between register- and survey-based analyses. Swedish examples suggest that it is
      unlikely that survey data can be used successfully to estimate the prevalence of
      serious alcohol-related social problems in society. Survey data may be more
      suitable for estimating risks associated with different drinking levels and
      drinking patterns in the general population on an ordinal level. However, there
      is still much room for improvement in the Swedish alcohol surveys that include
      questions on alcohol problems.

PMID- 11288472
TI  - Measuring drinking patterns: the experience of the last half century.
AB  - While there were earlier surveys of drinking behaviour, the modern tradition of
      these surveys dates back 50 years ago, and by the 1970s encompassed a number of
      countries. The paper reviews developments in the modern tradition of drinking
      surveys. One major tradition asks respondents about very recent drinking
      occasions, while the other asks the respondent to summarize the behavior over a
      longer period. While earlier analyses differentiated between frequency of
      drinking and quantity per occasion, this tradition was swamped by analyses in
      terms of an overall volume of drinking. Now, however, there is a renewed emphasis
      on patterns of drinking. Current developments in characterizing drinking patterns
      are summarized, with the conclusion that frequency of drinking at all, and
      frequency of heavier drinking occasions, are dimensions important both in terms
      of the social meaning of drinking and of the relation to potential consequences
      of drinking.

PMID- 11288473
TI  - Ways of measuring drinking patterns and the difference they make: experience with
      graduated frequencies.
AB  - This paper reviews methodological issues in assessing volume and pattern of
      alcohol consumption. It focuses on three measures developed at the Alcohol
      Research Group (ARG) to assess frequencies of drinking in a graduated series of
      quantity intervals, called the graduated quantity-frequency (QF) approach. The
      three measures include two reference periods, 30 days and 12 months, and use
      three distinct ways of assembling the graduated QF data. The Cahalan-Treiman 30
      day measure, developed for self-administered mail surveys, targets daily amounts
      of beverage alcohol, with thresholds asked in ascending order. The other two
      measures use descending quantity ranges. The Knupfer Series (KS) asks for three
      beverage-specific quantity levels. The Graduated Frequencies (GF) measure
      assesses intake of combined alcohol with five levels. Both are available in face
      to-face and telephone formats. All three measures inquire about consumption in
      the metric of "drinks," defined within the form or interview; each is useful for
      estimating volume and pattern of consumption. Methodological studies with the GF
      include comparisons with other measures, between- and within-subject interview
      comparisons, and qualitative protocol analyses designed to examine cognitive
      response processes. Uses for each measure are considered, and recommendations are
      made for improvement and more thorough specification of drinking patterns.

PMID- 11288474
TI  - Using daily reports to measure drinking and drinking patterns.
AB  - Daily measurements of drinking are used to measure alcohol consumption, validate
      retrospective questionnaires, and examine associations between drinking and other
      behaviors. The advantages of using daily reports include reducing retrospective
      biases and forgetting of drinking occasions; disadvantages include increased
      costs and potential for reactivity. Methodological issues to consider in using
      daily reports include reporting method (written, telephone, electronic),
      reporting interval, data collection period, respondent attrition, and missing
      data. Compared to retrospective reports, daily reports result in more reported
      drinking occasions but similar average quantity consumed, and correlations
      between retrospective and daily measures are generally high. The utility of daily
      reports depends on the research question and the purpose of the measurements.

PMID- 11288475
TI  - An alternative to standard drinks as a measure of alcohol consumption.
AB  - Despite the field's longstanding concern with underreporting of alcohol
      consumption, traditional survey questions encourage error because respondents
      often must calculate their number of drinks based on standard drink sizes that
      often do not match their own drinking style. This study considered how often
      respondents' self-defined drink sizes matched a 'standard' drink size based on
      approximately 12 g of ethanol for six different beverages. We also studied
      whether respondents could accurately judge the size of their drinks. Subjects
      were recruited and interviewed at urban prenatal clinics, health clinics, and via
      snowball referrals and community outreach in Los Angeles and the San Francisco
      Bay Area. Because of the urgency of accurate measurement of consumption during
      pregnancy, urban pregnant women from the groups most at risk for Fetal Alcohol
      Syndrome, Native Americans (n = 102) and African Americans (185), were targeted.
      A small comparison group of urban pregnant white women (n = 34) was included. One
      hour in-person interviews were conducted. Self-defined drink sizes were
      determined for each beverage consumed, using models and photographs of vessels.
      Frequent drinkers and the majority of women who reported drinking higher alcohol
      content beverages reported drinking larger-than-standard drink sizes. The median
      size of a malt liquor drink among the daily drinkers was almost three times as
      large as the standard, their fortified wine drinks were four times the standard,
      and their spirits drinks were six times the standard size. The majority of
      drinkers of each beverage were unable to accurately judge the size of their
      drinks, underestimating the number of fluid ounces by about 30%. Although the
      vessels methodology used here must be refined and tested further on other
      populations (e.g., men, nonpregnant women, and all ethnic groups), results
      suggest that determination of risk levels should be based on survey data that
      takes into consideration the beverage mix and the actual size of respondents'
      alcohol drinks.

PMID- 11288476
TI  - Alternative measures and models of hazardous consumption.
AB  - Hazardous alcohol consumption has been conceptualized (1) as all alcohol consumed
      on days when some threshold, usually approximately 60 g, is exceeded, and (2) as
      only that portion of intake that exceeds this threshold. The first measure is
      hypothesized to be a better predictor of acute alcohol-related outcomes, because
      of its greater capacity to discriminate between individuals who frequently exceed
      the hazardous threshold by a small amount and those who infrequently exceed the
      threshold by a large amount. To test this hypothesis, the two approaches were
      used to construct alternative estimates of a number of measures of hazardous
      consumption. Individually and in combination, these measures were compared in a
      series of multiplicative models predicting four alcohol-related outcomes:
      impaired driving, fighting, interpersonal problems and injuries. There was no
      consistent evidence for one approach being superior to the other as a predictor
      of these outcomes. In fact, the use of appropriate linear transformations of the
      consumption variables had a far greater effect on improving the proportion of
      variance explained. The most highly predictive models were those based on
      frequency of hazardous consumption, mean volume of hazardous intake consumed per
      hazardous drinking day, volume of nonhazardous intake and their interactions.
      Differences among models were small, and models using combinations of simple,
      easy-to-obtain measures performed nearly on a par with those utilizing far more
      complex measures.

PMID- 11288478
TI  - Video endoscopic database on WWW linking with ISDN.
AB  - We report here on a study of creating medical an image library comprised of
      simple but digitized gastrointestinal video-scope images, which were digitally
      compressed using MPEG-1 compression, and on the use of this library for clinical
      and educational applications. We have designed and installed a test-bed database
      (WWW) for gastrointestinal video-scope images linking with ISDN at 128 Kbps
      enables Internet access. This paper discusses its development, operation,
      problems, and educational and clinical use. A test-bed operation of the database
      was conducted by going on-line on the Internet and through an ISDN circuit (point
      to-point connection) at a speed of 128 Kbps. This dynamic image database proved
      to be effective in diagnostic imaging for endoscopic diagnosis and treatment. It
      also proved to be useful for improving the clinical levels of geographically
      isolated physicians.

PMID- 11288477
TI  - Concepts and items in measuring social harm from drinking.
AB  - Social epidemiological traditions of asking about problems related to drinking
      are considered. The issue of the attribution of the problem to drinking, and
      variations in formulations concerning this, are discussed. Social problems from
      drinking are inherently properties of social interactions, so that they are
      composed both of behaviour deemed problematic and of a reaction by another. Most
      items measuring social harm asked of the drinker him/herself are concerned with
      major social roles, and problems in the particular life area of the role (work,
      family, friendships, etc.). Some ask the respondent to attribute the problems to
      alcohol, some ask about others' attributions to alcohol, and some ask about
      "objective" problem indicators, although these usually have the respondent's
      attribution to drinking built in. The possibility of a more systematic way of
      covering different aspects of interactional problems, as reported by the drinker,
      is considered. Traditions of questioning the person on the other side of the
      interaction--i.e., items about others' troubles with drinking, and the effect of
      these on the respondent--are also discussed, and possibilities for bringing
      questions asked of the drinker and questions asked of interacting others into the
      same frame are considered.

PMID- 11288479
TI  - Software development for medical instrumentation.
AB  - Computer-assisted medical instrumentation has recently become more common. For
      accuracy and precision, the computer and interfacing circuit with the associated
      digital signal processing algorithm can be used for the evaluation of biological
      signal. The measurement system based on this structure has a very high degree of
      efficiency and flexibility because different algorithms can be used. In addition,
      the system can employ some newly developed software packages. This paper will
      submit a procedure for computer-assisted medical instrumentation, and also will
      show a specific application on blood flow.

PMID- 11288481
TI  - Classification of procedures in the domain of thoracic surgery--a study of
      reliability in coding.
AB  - This paper relates a study of reliability of coding of surgical procedures in the
      domain of thoracic surgery. The reliability measured is inter-coder variability
      in form of agreement. Four classifications were used by four physicians on 100
      patient cases. The classifications, having differing granularity and structure,
      were analyzed using a statistical method (kappa). These results are discussed and
      related to the differences between the classifications. One of the topics for
      discussion is how the granularity affects the degree of agreement, coupled to the
      usefulness of the classification. Also the concept of using formal methods for
      representing classifications is discussed, how this will affect how
      classifications are designed and used.

PMID- 11288480
TI  - Tutorial on technology transfer and survey design and data collection for
      measuring Internet and Intranet existence, usage, and impact (survey-2000) in
      acute care hospitals in the United States.
AB  - This paper provides a tutorial of technology transfer for management information
      systems in health care. Additionally it describes the process for a national
      survey of acute care hospitals using a random sample of 813 hospitals. The
      purpose of the survey was to measure the levels of Internet and Intranet
      existence and usage in acute care hospitals. The depth of the survey includes e
      commerce for both business to business and with customers. The relationships with
      systems approaches, user involvement, user satisfaction and decision-making will
      be studied. Changes with results of a prior survey conducted in 1997 can be
      studied and enabling and inhabiting factors identified. This information will
      provide benchmarks for hospitals to plan their network technology position and to
      set goals.

PMID- 11288482
TI  - An MRP system for surgical linen management at a large hospital.
AB  - Materials Requirements Planning (MRP) has been used extensively in manufacturing
      and other industries to improve on-time delivery and to reduce costs. In this
      paper, we illustrate how an MRP-type system was developed to monitor surgical
      linen at a large teaching hospital. We also describe a bar-code scanning 'tag and
      recapture' study to estimate total inventory. The hospital implemented several
      changes based upon our recommendations that resulted in time savings and a
      smoother flow of materials throughout the surgical linen supply chain.

PMID- 11288483
TI  - The impact of new antiretroic therapeutic schemes on the cost for AIDS treatment
      in Greece.
AB  - The paper attempts to evaluate the clinical and economic benefits between the
      administration of the dual and triple antiretroic schemes for the treatment of
      the HIV disease. Clinical and economic data are derived from patients
      hospitalized in 1996 and 1997 at the University Department of Dermatology and
      Venereology of Andreas Sygros Hospital. Methodology is based on the comparison of
      patients' nosological profile and direct annual cost before and after the
      administration of the triple treatment. The results of the study present that the
      triple combination therapy yields superior health outcomes, (decrease in the days
      of hospitalization and in the opportunistic disease events as well as fewer
      deaths and loss of production). Cost comparison presents a small decrease in the
      annual patient's cost, where all cost components are diminished, except the
      medication cost. A substitution of hospital care by drug therapy is revealed and
      a great change is taken place in the composition of the drugs' cost. Patient cost
      for antiretroic drugs has more than doubled from 1996 to 1997.

PMID- 11288484
TI  - An artificial neural network approach to diagnosing epilepsy using lateralized
      bursts of theta EEGs.
AB  - Determining the cause of seizures is a significant medical problem, as
      misdiagnosis can result in increased morbidity and even mortality of patients.
      The reported research evaluates the efficacy of using an artificial neural
      network (ANN) for determining epileptic seizure occurrences for patients with
      lateralized bursts of theta (LBT) EEGs. Training and test cases are acquired from
      examining records of 1,500 consecutive adult seizure patients. The small
      resulting pool of 92 patients with LBT EEGs requires using a jack-knife procedure
      for developing the ANN categorization models. The ANNs are evaluated for
      accuracy, specificity, and sensitivity on classification of each patient into the
      correct two-group categorization: epileptic seizure or non-epileptic seizure. The
      original ANN model using eight variables produces a categorization accuracy of
      62%. Following a modified factor analysis, an ANN model utilizing just four of
      the original variables achieves a categorization accuracy of 68%.

PMID- 11288485
TI  - [Functional involvement of cerebral diazepam binding inhibitor (DBI) in the
      establishment of drug dependence].
AB  - Mechanisms for formation of drug dependence and emergence of withdrawal syndrome
      are not yet fully understood despite of a huge accumulation of experimental and
      clinical data. Several clinical features of withdrawal syndrome are considered to
      be common (i.e., anxiety) among patients with drug dependence induced by
      different drugs of abuse. In this review, we have discussed the possibility of
      the functional involvement of diazepam binding inhibitor (DBI), an endogenous
      neuropeptide for benzodiazepine receptors with endogenously anxiogenic potential,
      in the development of drug dependence and emergence of its withdrawal symptom.
      The levels of DBI protein and its mRNA significantly increased in the brain
      derived from mice dependent on alcohol (ethanol), nicotine and morphine, and
      abrupt cessation of these drugs facilitated further increase in DBI expression.
      In the cases of nicotine- and morphine-dependent mice, concomitant administration
      of antagonists for nicotinic acetylcholine and opioid receptors, respectively,
      abolished the increase in DBI expression. Therefore, these alterations in DBI
      expression have a close relationship with formation of drug dependence and/or
      emergence of withdrawal syndrome and are considered to be a common biochemical
      process in drug dependence induced by different drugs of abuse.

PMID- 11288486
TI  - [Possible mechanisms in latent learning formation investigated by using mutant
      mice].
AB  - We examined possible mechanisms in the development of latent learning by methods
      of behavioral pharmacology and confirmed them by using mutant mice. Mice that
      received dopamine agonists, a noradrenergic neurotoxin or a traumatic brain
      injury showed impairment of latent learning. This impairment was suggested to be
      mediated by imbalance of dopaminergic and noradrenergic systems since the
      impairment was attenuated by a noradrenaline uptake inhibitor or a dopamine-D2
      antagonist. The heterozygous mice for the tyrosine hydroxylase (TH) gene and for
      the cyclic AMP (cAMP) response element binding protein (CREB) binding protein
      (CBP) gene showed impairment of latent learning in the water finding task. The
      spatial learning and hippocampal long-term potentiation (LTP) were normal in both
      the mutants. TH heterozygous mice showed a reduction of high K(+)-evoked
      noradrenaline release in the frontal cortex by the microdialysis technique and a
      reduction of cAMP of the brain cAMP content. The central noradrenergic systems
      and/or cAMP signal pathways play an important role in latent learning, but not
      spatial memory. In contrast with TH and CBP mutant mice, nociceptin-knockout mice
      showed an enhanced retention of latent learning in the water finding task,
      greater learning ability in the water maze task and larger LTP than wild-type
      mice. Such mice showed hyperfunction of dopaminergic systems in the cortex.
      Nociceptin itself induced latent learning impairment in wild-type mice. These
      results suggest that the nociceptin system seems to play negative roles in
      learning and memory. In conclusion, the results of mutant mice further supported
      our previous results of behavioral pharmacology and suggest that the alternation
      of catecholamine biosynthesis and cAMP signal pathways may play a key role in
      development of latent learning. They further suggest that the expression of genes
      mediated by phosphorylated CREB may be involved in the development of latent
      learning.

PMID- 11288487
TI  - [Molecular identification of the multispecific organic anion transporter family
      (the OAT family): the role in the pharmacokinetics and toxicokinetics].
AB  - The multispecific organic anion transporters have been indicated to be involved
      in the transmembrane transport of various anionic substances. The kidney and
      liver possess the distinct organic anion transport pathways for the elimination
      of potentially toxic anionic drugs and metabolites. In the kidney, proximal
      tubular cells actively excrete organic anions of both endogenous and exogenous
      origin. We have isolated the renal multispecific organic anion transporter, OAT1
      (organic anion transporter 1), from the rat kidney. OAT1 is a 551-amino acid
      residue protein with 12 putative membrane spanning domains. OAT1 mediates sodium
      independent, anion exchange for a variety of organic anions including p
      aminohippurate, cyclic nucleotides, prostanoides, dicarboxylates, and anionic
      drugs including beta-lactams, non-steroidal antiinflammatory drugs, diuretics and
      antiviral drugs. So far, three other isoforms have been identified. OATs comprise
      a new family of multispecific organic anion transporter, i.e., the OAT family.
      OATs show weak structural similarity to organic cation transporters (OCTs) and
      OCTN/carnitine transporters. All of the members of the OAT family are commonly
      expressed in the kidney, suggesting its significance in the renal organic anion
      excretion. In addition, OAT members appear to be responsible for the
      distribution/elimination of water soluble anionic drugs into/from the liver,
      brain and fetus.

PMID- 11288488
TI  - [NPY as a periarterial sympathetic transmitter in isolated vessel].
AB  - Double-peaked vasoconstrictor responses to periarterial nerve electrical
      stimulation (PNS) were readily induced in the condition of 30-s trains of pulses
      in isolated, perfused canine splenic artery, using the cannula insertion
      technique. P2X purinoceptors have been shown to be involved mainly in the 1st
      peaked response and alpha 1 adrenoceptors mostly in the 2nd one. Administrated
      NPY induced no direct vasoconstriction or only a slight vasoconstriction, and it
      inhibited the double-peaked vasoconstriction in a dose-related manner. A small
      dose of NPY Y1-receptor agonist, L-P NPY, readily potentiated the 2nd peaked
      response to PNS, and an increasing dose of LP-NPY did both the 1st and 2nd peaked
      responses. The 2nd peaked response was significantly inhibited by treatment with
      chloroethylclonidine (CEC), an alpha 1B-adrenoceptor antagonist, but the 1st
      peaked response was not influenced. On the other hand, an alpha 1A-antagonist,
      WB4101, rather potentiated the 2nd peaked response, although it did not modify
      the 1st one. Administered NA-induced constrictions were consistently inhibited by
      WB4101 but not by CEC. From these results, it is concluded that NPY inhibits the
      release of ATP and NA from periarterial nerve terminals by activation of
      presynaptic NPY Y2 receptors, and it potentiates PNS-induced vasoconstrictions
      via alpha 1B-adrenoceptors by activation of postjunctional NPY Y1 receptors in
      the canine splenic artery.

PMID- 11288489
TI  - [Pharmacological and physiological effects of ginseng on actions induced by
      opioids and psychostimulants].
AB  - Pharmacological and physiological effects of ginseng on actions induced by
      opioids and psychostimulants were summarized. Analgesic effects of opioids, such
      as morphine and U-50,488H, were blocked by ginseng in a non-opioid dependent
      manner. Furthermore, ginseng inhibited the tolerance to and dependence on
      morphine, and prevented the suppressive effect on the development of morphine
      tolerance caused by co-exposure to foot-shock stress, but not psychological
      stress. On the other hand, behavioral sensitization (reverse tolerance to
      ambulation-accelerating effect) to morphine, methamphetamine (MAP) and cocaine
      was also inhibited by ginseng. Interestingly, ginseng also inhibited the
      appearance of the recurrent phenomenon (reappearance of the sensitized state was
      observed at the time of readministration of MAP and cocaine even after a 30-day
      discontinuation of drug administration) of the effect of MAP and cocaine. The
      conditioned place preference of MAP and cocaine was completely blocked by
      ginseng. These findings provide evidence that ginseng may be useful clinically
      for the prevention of abuse and dependence of opioids and psychostimulants.

PMID- 11288490
TI  - [Isolated atrial tissue preparation for evaluation of cardioactive agents].
AB  - Isolated atrial tissue preparations provide convenient models for studying drug
      effects on the myocardium. However, there are several points we must be aware of.
      Interventions which change the beating rate also affect contractile force
      (Starling's Law). The membrane currents involved in the action potential as well
      as the excitation-contraction mechanisms differ between the atria and ventricle.
      Some membrane currents present only in the sino-atrial node and atrial myocardium
      may provide targets for novel bradycardiac agents and anti-atrial fibrillatory
      agents, respectively. The atrial tissue contains non-myocardial cells such as
      autonomic neurons and endocardial endothelial cells, which may be involved in the
      responses to various pharmacological stimuli.

PMID- 11288491
TI  - [The "Balthasar" pediatric hospice].

PMID- 11288492
TI  - [Kinesthetic infant handling in neonatology].

PMID- 11288493
TI  - [Violence against children: to see, to notice, to help].

PMID- 11288494
TI  - [To humanise death--not to legalize killing].

PMID- 11288495
TI  - [Nursing documentation in endoscopy].

PMID- 11288496
TI  - [Everyday conflicts at the first aid station].

PMID- 11288497
TI  - [Why do men die at a younger age?].

PMID- 11288498
TI  - [Nursing education--new thinking? New action?].

PMID- 11288499
TI  - Playground injuries in children: a review and Pennsylvania Trauma Center
      experience.
AB  - ISSUES AND PURPOSE: To describe patient demographics, injury characteristics, and
      circumstances of playground injuries in children admitted to Pennsylvania trauma
      centers and to identify injury prevention strategies. DESIGN AND METHODS:
      Retrospective, descriptive study of 234 children ages 1 to 18 years sustaining
      playground-related injuries and whose hospital data were entered into the
      Pennsylvania Trauma Outcome Study. RESULTS: Most of the injuries occurred between
      April and September (77%), and noon to 6 P.M. (69%). Falls from playground
      equipment constituted the highest proportion of incidents (73%). Of 421 injuries
      (M = 1.8/patient), most were upper extremity (n = 117) and head (n = 110)
      injuries. PRACTICE IMPLICATIONS: Nurses can advocate for playground safety by
      teaching children to play safely and recommending age-appropriate equipment and
      protective surfacing.

PMID- 11288501
TI  - Evidence is information you can count on.

PMID- 11288500
TI  - Bone loss in adolescents using Depo-Provera.
AB  - ISSUES AND PURPOSE: Contraceptive methods that decrease bone density in a
      population already deficient in calcium are a rising concern in women's health.
      CONCLUSIONS: Use of Depo-Provera (DMPA) significantly decreases bone mass density
      (BMD) in normal adolescents up to the age of 21. DMPA is often used in
      adolescents with disabilities who may already be at high risk for osteoporosis.
      The effects are likely to be similar to that in able-bodied adolescents, but
      research is limited. PRACTICE IMPLICATIONS: Through early identification of risk
      factors in able-bodied and disabled adolescents, primary care providers
      considering the use of DMPA in adolescents can optimize BMD by providing adequate
      nutritional assessment, counseling on nutritional sources of calcium, calcium
      supplementation, guidance on exercise, and alcohol and smoking prevention or
      cessation.

PMID- 11288502
TI  - Eliminating health disparities for racial and ethnic minorities: a nursing agenda
      for children.

PMID- 11288503
TI  - Television viewing and children's health.

PMID- 11288504
TI  - Grassroots advocacy in action: successes and opportunities for pediatric nurses.

PMID- 11288505
TI  - A nurse's role in helping well children cope with a parent's serious illness
      and/or hospitalization.

PMID- 11288506
TI  - Publication Committee restructuring: streamlining efforts to better serve SPN
      members.

PMID- 11288507
TI  - Clinical and economic outcomes of infants receiving breast milk in the NICU.
AB  - ISSUES AND PURPOSE: This study compared clinical and economic outcomes for
      infants who were exclusively fed breast milk and infants who were fed commercial
      formula. DESIGN AND METHODS: A retrospective medical record review from a
      regional neonatal intensive care unit (N = 80) using consultation logs from the
      lactation coordinator and a matched sample of formula-fed infants. RESULTS:
      Neither clinical (weight gain, length of stay, days of parenteral nutrition) nor
      economic outcomes (direct variable costs, net revenue) differed significantly
      between the groups. PRACTICE IMPLICATIONS: While it may not be possible to
      demonstrate sufficient cost savings while the infant resides within the NICU to
      justify a lactation coordinator, long-term clinical and economic outcomes may be
      sensitive to this specialized nursing service.

PMID- 11288508
TI  - Vaccination of animals against Mycobacterium bovis.
AB  - Vaccination could potentially be used as a practical means of controlling bovine
      tuberculosis in countries in which a wildlife reservoir of the disease is
      present, and also in those countries which cannot afford conventional control
      strategies. An understanding of the processes involved in the protective immune
      response to tuberculosis is desirable for the rational development and testing of
      new vaccines for tuberculosis. The authors review current knowledge regarding the
      processes involved in protective immune responses to tuberculosis, much of which
      has been derived from studies in mice. This knowledge is discussed in relation to
      the problem of using vaccination to induce protective immunity in cattle, deer
      and wildlife. Challenge models have now been developed to test candidate vaccines
      in many domestic animals and wildlife species and these models are being used to
      evaluate tuberculosis vaccines. Most studies of the efficacy of tuberculosis
      vaccines in target animals have focused on the use of bacillus Calmette-Guerin
      (BCG), an attenuated strain of Mycobacterium bovis. Recent advances in immunology
      and the molecular biology of mycobacteria have greatly increased the options for
      candidate vaccines and future studies will test new types of vaccines including
      new attenuated strains of M. bovis, sub-unit protein vaccines and recombinant
      deoxyribonucleic acid vaccines. Several of these vaccines have shown promising
      results when tested in small animal models. Although progress has been made in
      the development of vaccine delivery systems for animals, the technical problems
      associated with vaccination of wildlife remain a challenge.

PMID- 11288509
TI  - Mycobacterium avium subsp. paratuberculosis: pathogen, pathogenesis and
      diagnosis.
AB  - Johne's disease, or paratuberculosis, is a chronic intestinal infection caused by
      Mycobacterium avium subsp. paratuberculosis. The usually fatal disease is
      characterised by cachexia, and in some species diarrhoea, after a long pre
      clinical phase. Treatment is ineffective and economically impracticable. The
      infection primarily affects domestic and free-ranging ruminants, but has also
      been reported in primates, rabbits, stoats and foxes. Since paratuberculosis is
      often subclinical, under-reporting is suspected, even though the disease is
      notifiable in numerous countries. Herd prevalence of bovine paratuberculosis in
      Europe ranges from 7% to 55%. In the United States of America, herd prevalence is
      strongly associated with herd size; 40% of herds of more than 300 head were found
      to be infected. In Australia, reported dairy herd infection rates range between
      9% and 22%. Paratuberculosis in domestic livestock entails significant economic
      losses due to several factors (e.g. reduced production, premature culling and
      increased veterinary costs). Free-ranging and captive wildlife are also at risk
      from paratuberculosis.

PMID- 11288510
TI  - Control of Mycobacterium avium subsp. paratuberculosis infection in agricultural
      species.
AB  - Paratuberculosis or Johne's disease is a chronic intestinal disease caused by
      Mycobacterium avium subsp. paratuberculosis, which continues to spread in
      agricultural species. Control of paratuberculosis is challenging and should not
      be underestimated. Due to the long incubation period of the infection, disease is
      largely subclinical in domesticated livestock. Hence, direct effects on animal
      productivity and welfare are often masked and may appear insufficient to justify
      large investments in control programmes by individual farmers, livestock
      industries or governments. Furthermore, in some countries the main effects of the
      disease are indirect, resulting from the impact of market discrimination against
      herds and flocks known to be infected, or from the control measures enforced to
      reduce transmission. In such circumstances, producers may be unwilling to co
      operate with surveillance that may detect infection in herds or flocks. As
      control programmes are rarely successful in eliminating the infection from a herd
      or flock in the short term without an aggressive and costly programme, financial
      and community support assists producers to deal with the challenge. Successful
      prevention and control depends on animal health authorities and livestock
      industries acquiring a good understanding of the nature and epidemiology of
      infection, and of the application of tools for diagnosis and control. Building
      support for control programmes under the leadership of the affected livestock
      industries is critical, as programmes are unlikely to be successful without
      ongoing political will, supported by funding for research, surveillance and
      control.

PMID- 11288511
TI  - Mycobacteriosis in birds.
AB  - Avian mycobacteriosis is an important disease which affects companion, captive
      exotic, wild and domestic birds. The disease is most commonly caused by
      Mycobacterium avium and Mycobacterium genavense. Lesions are typically found in
      the liver and gastrointestinal tract, although many other organ systems can
      potentially be affected. The authors review those species of Mycobacterium
      reported to affect birds, the epidemiology of avian mycobacteriosis,
      immunological responses to mycobacterial infection, ante- and post-mortem
      diagnosis, treatment and prevention or control of the disease.

PMID- 11288512
TI  - Mycobacterium avium and Mycobacterium intracellulare infection in mammals.
AB  - Mycobacterium avium subsp. avium and M. intracellulare are ubiquitous organisms
      in the environment. The reservoir of M. avium subsp. avium is generally accepted
      to be environmental, in particular, water and soil are sources of the organism.
      In contrast to M. avium infection in wild and domestic birds, M. avium infection
      in mammals occurs only sporadically and is rarely transmissible. Generalised
      disease is usually uncommon, owing to the non-progressive, chronic character of
      the infection. However, some cases of disseminated disease have been reported,
      e.g. in captive non-domestic hoofed animals as well as in immunosuppressed dogs
      and cats. The majority of M. avium and M. intracellulare infections in livestock
      are detected at slaughter and the diagnosis is confirmed by bacteriological
      procedures. Condemnation of affected portions of the carcass can result in
      significant economic losses, although gross lesions are mostly restricted to
      lymph nodes close to the alimentary tract. Successful treatment with antibiotics
      in combination with surgery has been reported in some affected domestic cats, but
      is not considered to be effective or economical in other species. In the past,
      differentiation of M. avium bacteria from the closely related M. avium subsp.
      paratuberculosis was based on the mycobactin dependence and prolonged incubation
      period of the latter. More recently, amplification of the genomic insertion
      sequence IS900 has proved to be a powerful tool for identification of M. avium
      subsp. paratuberculosis. The potential zoonotic importance of M. avium infections
      has been indicated, but requires clarification.

PMID- 11288513
TI  - The mycobacteria: an introduction to nomenclature and pathogenesis.
AB  - Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M.
      leprae, are diseases known since antiquity. In developing countries, tuberculosis
      is still the leading cause of mortality due to an infectious disease.
      Taxonomically, mycobacteria belong to the genus Mycobacterium, which is the
      single genus within the family of Mycobacteriaceae, in the order Actinomycetales.
      Actinomycetales include diverse micro-organisms, but mycobacteria and allied taxa
      are easily distinguished on the basis of the ability to synthesise mycolic acids.
      Mycobacterial species are traditionally differentiated on the basis of phenotypic
      characteristics, and the authors provide an updated list of the biochemical tests
      currently employed and the culture properties that help to discriminate among
      various species of mycobacteria. However, as the phenotypic characteristics do
      not allow precise identification of all species, recent molecular taxonomical
      approaches for mycobacterial classification and phylogeny are also described.
      Mycobacteria are also a leading cause of infection in various domesticated
      animals and wildlife. The authors briefly describe the mycobacteria involved in
      animal infections, the wildlife reservoirs and strategies to control bovine
      tuberculosis, and the use of molecular tools for diagnostics and epidemiology of
      mycobacterial infections in animals. The characteristic of intracellular
      parasitism is discussed, in addition to the fate of pathogenic mycobacteria that
      have the ability to grow inside phagosomes and phagolysosomes of infected host
      macrophages. The mycobacterial cell envelope, which is a complex tripartite
      structure containing a high proportion of lipids (approximately 30% to 40% of the
      total weight) could play a crucial role in the adaptation of mycobacteria to
      intracellular growth and survival, immune modulation and drug resistance.

PMID- 11288514
TI  - Mycobacterium leprae and Mycobacterium lepraemurium infections in domestic and
      wild animals.
AB  - Mycobacterium leprae, the aetiological agent of leprosy in humans, gives rise to
      a chronic granulomatous disease that affects primarily the skin and peripheral
      nerves, and secondarily some internal organs such as the testis and the eye;
      viscera are seldom involved. Depending on host resistance, leprosy may present as
      a benign disease (tuberculoid leprosy) or as a malignant disease (lepromatous
      leprosy), with a spectrum of intermediate stages appearing between the two.
      Immunity against leprosy depends on the cell-mediated immunity of the host, and
      this is severely compromised in the malignant (lepromatous) form of leprosy.
      Although culture of M. leprae has never been achieved in artificial media, the
      bacterium may be grown in several experimental animals, including the armadillo,
      non-human primates, and to a certain extent, rodents. Naturally acquired leprosy
      has been reported in wild nine-banded armadillos (Dasypus novemcinctus) and in
      three species of non-human primates (chimpanzees [Pan troglodytes], sooty
      mangabey monkeys [Cercocebus atys] and cynomolgus macaques [Macaca
      fascicularis]), thus qualifying leprosy as a zoonosis. Murine leprosy is a
      leprosy-like disease of rats and mice, caused by Mycobacterium lepraemurium. The
      disease affects primarily viscera and the skin, and very rarely peripheral
      nerves. Depending on the host strain, rodent leprosy may also evolve as
      'lepromatous' or 'tuberculoid' leprosy, and strains of mouse that develop
      intermediate forms of the disease may exist. Growth of M. lepraemurium on
      conventional media for mycobacteria is not successful, but the bacterium has been
      cultured on an egg yolk-based medium. Naturally acquired murine leprosy has been
      observed in rats, mice and cats, but not in humans or any other species. Thus, in
      contrast to human leprosy, murine leprosy is not a zoonosis.

PMID- 11288515
TI  - Mycobacterium ulcerans in wild animals.
AB  - Mycobacterium ulcerans infection, or Buruli ulcer, is the third most frequent
      mycobacterial disease in humans, often causing serious deformities and
      disability. The disease is most closely associated with tropical wetlands,
      especially in west and central Africa. Most investigators believe that the
      aetiological agent proliferates in mud beneath stagnant waters. Modes of
      transmission may involve direct contact with the contaminated environment,
      aerosols from water surfaces, and water-dwelling fauna (e.g. insects). Person-to
      person transmission is rare. Trauma at the site of skin contamination by M.
      ulcerans appears to play an important role in initiating disease. Once introduced
      into the skin or subcutaneous tissue, M. ulcerans multiplies and produces a toxin
      that causes necrosis. However, the type of disease induced varies from a
      localised nodule or ulcer, to widespread ulcerative or non-ulcerative disease and
      osteomyelitis. Although culture of M. ulcerans from a patient was first reported
      in 1948, attempts to culture the mycobacterium from many specimens of flora and
      fauna have been unsuccessful. Failure to cultivate this organism from nature may
      be attributable to inadequate sampling, conditions of transport, decontamination
      and culture of this fastidious heat-sensitive organism, and to a long generation
      time relative to that of other environmental mycobacteria. Nevertheless, recent
      molecular studies using specific primers have revealed M. ulcerans in water, mud,
      fish and insects. Although no natural reservoir has been found, the possibility
      that M. ulcerans may colonise microfauna such as free-living amoebae has not been
      investigated. The host range of experimental infection by M. ulcerans includes
      lizards, amphibians, chick embryos, possums, armadillos, rats, mice and cattle.
      Natural infections have been observed only in Australia, in koalas, ringtail
      possums and a captive alpaca. The lesions were clinically identical to those
      observed in humans. Mycobacterium ulcerans infection is a rapidly re-emerging
      disease in some developing tropical countries. The re-emergence may be related to
      environmental and socioeconomic factors, for example, deforestation leading to
      increased flooding, and population expansion without improved agricultural
      techniques, thus putting more people at risk. Eradication of diseases related to
      these factors is difficult. Whether wild animals have a role in transmission is
      an important question that, to date, has been virtually unexplored. To address
      this question, surveys of wild animals are urgently required in those areas in
      which Buruli ulcer is endemic.

PMID- 11288516
TI  - Mycobacterial infections in domestic and wild animals due to Mycobacterium
      marinum, M. fortuitum, M. chelonae, M. porcinum, M. farcinogenes, M. smegmatis,
      M. scrofulaceum, M. xenopi, M. kansasii, M. simiae and M. genavense.
AB  - The epidemiology and the natural distribution of Mycobacterium marinum, M.
      fortuitum, M. chelonae, M. porcinum, M. farcinogenes, M. smegmatis, M.
      scrofulaceum, M. xenopi, M. kansasii, M. simiae and M. genavense are described.
      In addition to the bacteriological, biochemical and genetic characteristics, the
      authors review the pathology of these species, including the natural and
      experimental diseases and the accompanying lesions, diagnosis, antibiotic
      sensitivities and treatment of animal infections caused by these mycobacteria.

PMID- 11288517
TI  - Mycobacterium tuberculosis in zoo and wildlife species.
AB  - Tuberculosis caused by Mycobacterium tuberculosis and M. tuberculosis-like
      organisms has been identified in a wide range of species, including non-human
      primates, elephants and other exotic ungulates, carnivores, marine mammals and
      psittacine birds. Disease associated with M. tuberculosis has occurred mostly
      within captive settings and does not appear to occur naturally in free-living
      mammals. Mycobacterium tuberculosis probably originated as an infection of
      humans, but from the zoonotic standpoint, non-human primates, Asian elephants and
      psittacine birds have the potential to transmit this disease to humans. However,
      the overall prevalence of disease in these susceptible species is low and
      documented transmissions of M. tuberculosis between animals and humans are
      uncommon. Mycobacterium tuberculosis causes progressive pulmonary disease in
      mammals and a muco-cutaneous disease in parrots. In all cases, the disease can
      disseminate and be shed into the environment. Diagnosis in living animals is
      based on intradermal tuberculin testing in non-human primates, culturing trunk
      secretions in elephants, and biopsy and culture of external lesions in parrots.
      Ancillary testing with deoxyribonucleic acid probes and nucleic acid
      amplification, and enzyme-linked immunosorbent assays have been adapted to some
      of these species with promising results. Additionally, new guidelines for
      controlling tuberculosis in elephants in the United States of America, and
      programmes for tuberculosis prevention in animal handlers have been established.

PMID- 11288518
TI  - In vivo and in vitro diagnosis of Mycobacterium bovis infection.
AB  - The intradermal delayed type hypersensitivity (DTH) skin test, using purified
      protein derivative from culture of M. bovis or M. avium, is the most frequently
      used test for diagnosis of tuberculosis or detection of M. bovis infection in
      cattle. Many improvements have been made to the original tuberculin test, and
      molecular approaches to identify and clone antigens may lead to improved
      specificity and sensitivity of DTH skin tests. Recent advances in technology have
      allowed the development of new in vitro techniques, such as antibody-based, cell
      mediated immunity-based and nucleic acid-based diagnostics, which allow more
      rapid diagnosis than bacteriological culture. The choice of diagnostic technique
      should consider both the population being investigated (e.g. apparently healthy
      animals or a herd with a high prevalence of clinical infection) and the aim of
      the testing (e.g. the screening of healthy animals or confirmation of infection
      in animals strongly suspected to be infected). Moreover, any evaluation of a
      diagnostic test must use a carefully selected control population which is
      representative of the population to be tested in terms of relative proportions of
      infected and non-infected animals.

PMID- 11288519
TI  - Epidemiology of selected mycobacteria that infect humans and other animals.
AB  - This paper provides a summary of salient clinical and epidemiological features of
      selected mycobacterial diseases that are common to humans and other animals.
      Clinical and diagnostic issues are discussed and related to estimates of the
      incidence and prevalence of these diseases among humans. Source of infection,
      route of transmission and control measures are also presented. The mycobacteria
      discussed in this paper are Mycobacterium bovis, M. ulcerans, M. leprae and M.
      avium complex, although this is by no means a complete list of the mycobacteria
      common to humans and other animals. Certain generalities can be made regarding
      these species of mycobacteria and their occurrence in humans and other animals;
      firstly, current understanding of the epidemiology and control of many of the
      resultant diseases is incomplete; secondly, environmental sources other than
      animal reservoirs may play a role in transmission (with M. leprae perhaps being
      the exception); and thirdly, the incidence and prevalence of these diseases in
      many countries of the world are unclear, principally because of the complexity of
      diagnosis and lack of reporting systems.

PMID- 11288520
TI  - Treatment of mycobacterial infections.
AB  - Treatment of mycobacterial infections differs from that of other bacterial
      diseases due to several properties possessed by the mycobacteria and the host. A
      hallmark of mycobacteria is the complex lipid-rich cell envelope that protects
      the organism from both the host response and antimycobacterial therapy. In
      addition, mycobacteria are facultative intracellular parasites which generally
      cause a more chronic type of disease. These properties add greater constraints to
      efficient therapy. To be effective, drugs must be able to penetrate the host
      macrophage and preferably have reduced toxicity and be effective at low doses to
      allow prolonged therapy. The author presents the general properties of the
      pathogen/host relationship in mycobacterial infections, in addition to the
      therapeutic choices available and the mechanisms of action involved in treatment.
      The evolution of technology for antimycobacterial therapy is illustrated by a
      discussion of new strategies being developed for the treatment of mycobacterial
      infections.

PMID- 11288521
TI  - Mycobacterium bovis infection and control in domestic livestock.
AB  - Bovine tuberculosis, caused by Mycobacterium bovis, is a well-known zoonotic
      disease which affects cattle world-wide. The public health risk has been
      alleviated in many countries by the introduction of pasteurisation, but the
      disease continues to cause production losses when poorly controlled. The Office
      International des Epizooties classifies bovine tuberculosis as a List B disease,
      a disease which is considered to be of socio-economic or public health importance
      within countries and of significance to the international trade of animals and
      animal products. Consequently, most developed nations have embarked on campaigns
      to eradicate M. bovis from the cattle population or at least to control the
      spread of infection. The success of these eradication and control programmes has
      been mixed. Mycobacterium bovis infects other animal species, both domesticated
      and wild, and this range of hosts may complicate attempts to control or eradicate
      the disease in cattle.

PMID- 11288523
TI  - [Study patients recover better from stroke. L-dopa: doping for the apolpexy
      brain? (interview by Waldtraud Paukstadt].

PMID- 11288522
TI  - Mycobacterium bovis in free-living and captive wildlife, including farmed deer.
AB  - Mycobacterium bovis has been isolated from a wide range of wildlife species, in
      addition to domestic animals. This review examines the role played by various
      species in the maintenance of M. bovis in wildlife communities and the spread to
      domestic animals. Badgers (Meles meles), brushtail possums (Trichosurus
      vulpecula), deer (Odocoileus virginianus), bison (Bison bison) and African
      buffalo (Syncerus caffer) are examples of wildlife that are maintenance hosts of
      M. bovis. The importance of these hosts has been highlighted by the growing
      realisation that these animals can represent the principal source of infection
      for both domestic animals and protected wildlife species. The range of methods
      for controlling M. bovis in wildlife is limited. While population control has
      been used in some countries, this approach is not applicable in many situations
      where protected wildlife species are concerned. Vaccination is a potential
      alternative control method, although as yet, no practical, effective system has
      been developed for vaccinating wildlife against bovine tuberculosis. Tuberculosis
      caused by M. bovis has also been a problem in captive wildlife and in recently
      domesticated animals such as farmed deer. Control of M. bovis in this group of
      animals is dependent on the judicious use of diagnostic tests and the application
      of sound disease control principles. The advances in the development of bovine
      tuberculosis vaccines for cattle and farmed deer may offer valuable insights into
      the use of vaccination for the control of tuberculosis in a range of captive
      wildlife species.

PMID- 11288525
TI  - [ZDF magazine "Wiso" reveals fraudulent claimants. Scandalous commentary].

PMID- 11288524
TI  - [Why colleagues with depression treat themselves so poorly. We physicians are
      heros after all and must function! ].

PMID- 11288526
TI  - [Rectal bleeding: when is it a sign of colon cancer?].

PMID- 11288527
TI  - [Physicians wash their hands too infrequently].

PMID- 11288528
TI  - [Properly classifying skin changes. Exanthema--what is what?].
AB  - Exanthema is characterized by extensive generalized eruptions of the skin and
      mucosa that show a typical temporal spread. Potential noxae include medications,
      foodstuffs, infections (viral, bacterial, mycotic, parasitic), and malignancies,
      but unexplained causes may also present. A knowledge of the cutaneous changes may
      contribute decisively to ensuring that specific diagnostic and therapeutic
      measures are initiated without delay.

PMID- 11288529
TI  - [Symptomatic therapy of exanthema. Finding the proper externum].
AB  - In the treatment of exanthems, the first step is the elimination of the causal
      agent. Of great importance also is the symptomatic treatment of the cutaneous
      changes and such associated symptoms as itching and pain. The choice of the
      appropriate external medication and its vehicle will depend on the clinical
      findings, skin type, and the location of the skin lesions. The most important
      therapeutic principles are discussed taking drug-induced exanthema, acute
      urticaria and (herpes) zoster as examples.

PMID- 11288530
TI  - [Emergencies in general practice, 4. Sudden deafness: follow the guidelines].

PMID- 11288531
TI  - [Hay fever and food allergies. When the immune system runs amok].

PMID- 11288532
TI  - [Follow-up in diabetes. This "minimal program" should be followed].

PMID- 11288533
TI  - [Diagnosis of schizophrenia. Puberty-related crisis or psychosis?].

PMID- 11288534
TI  - [Diagnostic quiz. Fever with heart murmur. Aortic valve endocarditis].

PMID- 11288535
TI  - [Are essential oils effective therapeutic agents? Complementary medicine
      procedure: aromatherapy].

PMID- 11288536
TI  - [Pleasant added effect. Losartan improves sex in hypertension].

PMID- 11288537
TI  - [When hypertension damages microcirculation. A-II-antagonist corrects damage,
      beta blocker does not].

PMID- 11288538
TI  - [Current recommendations in peripheral arterial occlusive disease. When walking
      is no longer enough].

PMID- 11288539
TI  - [Chronic sinusitis, polyps, snoring. Topical glucocorticosteroid can relieve
      symptoms].

PMID- 11288540
TI  - [In liver cirrhosis, not every "ammonia lowering drug" improves neuropsychiatric
      deficit].

PMID- 11288541
TI  - [Severe heart failure. Carvedilol lowers mortality].

PMID- 11288542
TI  - [Bone metastasis. Can a new bisphosphonate offer control?].

PMID- 11288543
TI  - [Food hypersensitivity. Frequently suspected, often overlooked].

PMID- 11288544
TI  - Preventing transient increases in ICP.

PMID- 11288545
TI  - Managing a venous ulcer.

PMID- 11288546
TI  - Central venous catheters and cardiac tamponade.

PMID- 11288547
TI  - Hepatitis C. Speaking out about the silent epidemic.

PMID- 11288548
TI  - Nursing2001 salary survey.

PMID- 11288549
TI  - What you need to know about the new BLS guidelines. Now you'll give stroke
      victims the same priority as those having an MI. Here's what else has changed.
AB  - Major changes to basic life support (BLS) and advanced cardiac life support
      (ACLS) practice have been approved, and you'll soon be receiving official update
      training. In this summary of the recommendations, we'll give you a head start on
      learning about changes to BLS protocols for health care professionals. Next
      month, we'll cover changes to ACLS guidelines.

PMID- 11288550
TI  - The woman inside. Denise showed me a side of schizophrenia that few professionals
      ever sea.

PMID- 11288551
TI  - Tissue adhesives. A sticky solution to wound repair.

PMID- 11288553
TI  - Yes. You need a lawyer.

PMID- 11288552
TI  - Helping high-risk surgical patients beat the odds.

PMID- 11288554
TI  - Walking the hundred-mile road. A parable for someone who's nearing the end of
      life.

PMID- 11288555
TI  - Action stat. Disseminated intravascular coagulation.

PMID- 11288556
TI  - Teaching patients about lipid levels.

PMID- 11288557
TI  - Reviewing the immune system.

PMID- 11288559
TI  - Learning about ginkgo.

PMID- 11288558
TI  - Protecting yourself during pregnancy. Guard your unborn child from dangerous
      infections with these guidelines.

PMID- 11288560
TI  - Helicobacter pylori.

PMID- 11288561
TI  - Going for the gold.

PMID- 11288562
TI  - Resisting care.

PMID- 11288563
TI  - . . . About vital signs monitors. Find out what monitors measure . . . how
      devices are integrated . . . and more.

PMID- 11288565
TI  - Documenting adverse incidents.

PMID- 11288564
TI  - Clarithromycin and CNS disturbances.

PMID- 11288566
TI  - Taking the sting out of trigeminal neuralgia.

PMID- 11288567
TI  - "When it's her time to go...".

PMID- 11288568
TI  - Interpretation of actinide-distribution data obtained from non-destructive and
      destructive post-test analyses of an intact-core column of Culebra dolomite.
AB  - The US Department of Energy (DOE), with technical assistance from Sandia National
      Laboratories, has successfully received EPA certification and opened the Waste
      Isolation Pilot Plant (WIPP), a nuclear waste disposal facility located
      approximately 42 km east of Carlsbad, NM. Performance assessment (PA) analyses
      indicate that human intrusions by inadvertent, intermittent drilling for
      resources provide the only credible mechanisms for significant releases of
      radionuclides from the disposal system. For long-term brine releases, migration
      pathways through the permeable layers of rock above the Salado formation are
      important. Major emphasis is placed on the Culebra Member of the Rustler
      Formation because this is the most transmissive geologic layer overlying the WIPP
      site. In order to help quantify parameters for the calculated releases,
      radionuclide transport experiments have been carried out using intact-core
      columns obtained from the Culebra dolomite member of the Rustler Formation within
      the WIPP site. This paper deals primarily with results of analyses for 241Pu and
      241Am distributions developed during transport experiments in one of these cores.
      Transport experiments were done using a synthetic brine that simulates Culebra
      brine at the core recovery location (the WIPP air-intake shaft (AIS)). Hydraulic
      characteristics (i.e., apparent porosity and apparent dispersion coefficient) for
      intact-core columns were obtained via experiments using the conservative tracer
      22Na. Elution experiments carried out over periods of a few days with tracers
      232U and 239Np indicated that these tracers were weakly retarded as indicated by
      delayed elution of the species. Elution experiments with tracers 241Pu and 241Am
      were attempted but no elution of either species has been observed to date,
      including experiments of many months' duration. In order to quantify retardation
      of the non-eluted species 241Pu and 241Am after a period of brine flow, non
      destructive and destructive analyses of one intact-core column were carried out
      to determine distribution of these actinides in the rock. Analytical results
      indicate that the majority of the 241Am remained very near the injection surface
      of the core (possibly as a precipitate), and that the majority of the 241Pu was
      dispersed with a very high apparent retardation value. The 241Pu distribution is
      interpreted using a single-porosity advection-dispersion model, and an
      approximate retardation value is reported.

PMID- 11288569
TI  - Rock matrix diffusivity determinations by in-situ electrical conductivity
      measurements.
AB  - A fast method to determine rock matrix diffusion properties directly in the
      bedrock would be valuable in the investigation of a possible site for disposal of
      nuclear waste. An "effective diffusivity borehole log" would provide important
      information on the variability of this entity over the area studied. As opposed
      to traditional matrix diffusion laboratory experiments, electrical conductivity
      measurements are fast, inexpensive and also easy to carry out in-situ. In this
      study, electrical resistivity data from borehole logging, as well as from
      measurements on the actual core, is evaluated with the purpose of extracting
      matrix diffusivity data. The influence of migration of ions in the electrical
      double layer, which can be of great importance in low ionic strength pore water,
      is also considered in evaluating the in-situ data to accurately determine the
      effective pore diffusivity. The in-situ data compare fairly well to those
      measured in the rock core.

PMID- 11288570
TI  - Solute transport properties of compacted Ca-bentonite used in FEBEX project.
AB  - The present Spanish concept of a deep geological high level waste repository
      includes an engineered clay barrier around the canister. The clay presents a very
      high sorption capability for radionuclides and a very small hydraulic
      conductivity, so that the migration process of solutes is limited by sorption and
      diffusion processes. Therefore, diffusion and distribution coefficients in
      compacted bentonite (i.e. in "realistic" liquid to solid ratio conditions) are
      the main parameters that have to be obtained in order to characterise solute
      transport that could be produced after the canister breakdown. Through-Diffusion
      (TD) and In-Diffusion (ID) experiments with HTO, Sr, Cs and Se were carried out
      using compacted FEBEX bentonite, which is the reference material for the Spanish
      concept of radioactive waste disposal. Experiments were interpreted by means of
      available analytical solutions that allow the estimation of diffusion
      coefficients and, in some cases, distribution coefficients. Analytical solutions
      are simple to use, but rely on hypotheses that do not hold in all the
      experiments. These experiments were interpreted also using an automatic parameter
      estimation code that overcomes the limitations of analytical solutions. Numerical
      interpretation allows the simultaneous estimation of porosity, diffusion and
      distribution coefficients, accounts for the role of porous sinters and time
      varying boundary concentrations, and can use different types of raw concentration
      data.

PMID- 11288572
TI  - Apparent diffusion coefficients and chemical species of neptunium (V) in
      compacted Na-montmorillonite.
AB  - Diffusion of neptunium (V) in compacted Na-montmorillonite was studied through
      the non-steady state diffusion method. In this study, two experimental attempts
      were carried out to understand the diffusion mechanism of neptunium. One was to
      establish the diffusion activation energy, which was then used to determine the
      diffusion process in the montmorillonite. The other was the measurement of the
      distribution of neptunium in the montmorillonite by a sequential batch
      extraction. The apparent diffusion coefficients of neptunium in the
      montmorillonite at a dry density of 1.0 Mg m-3 were from 3.7 x 10(-12) m2 s-1 at
      288 K to 9.2 x 10(-12) m2 s-1 at 323 K. At a dry density of 1.6 Mg m-3, the
      apparent diffusion coefficients ranged between 1.5 x 10(-13) m2 s-1 at 288 K and
      8.7 x 10(-13) m2 s-1 at 323 K. The activation energy for the diffusion of
      neptunium at a dry density of 1.0 Mg m-3 was 17.5 +/- 1.9 kJ mol-1. This value is
      similar to those reported for diffusion of other ions in free water, e.g., 18.4
      and 17.4 kJ mol-1 for Na+ and Cl-, respectively. At a dry density of 1.6 Mg.m-3,
      the activation energy was 39.8 +/- 1.9 kJ mol-1. The change in the activation
      energy suggests that the diffusion process changes depending on the dry density
      of the compacted montmorillonite. A characteristic distribution profile was
      obtained by the sequential extraction procedure for neptunium diffused in
      compacted montmorillonite. The estimated fraction of neptunium in the pore water
      was between 3% and 11% at a dry density of 1.6 Mg m-3 and at a temperature of 313
      K. The major fraction of the neptunium in the montmorillonite was identified as
      neptunyl ions sorbed on the outer surface of the montmorillonite. These findings
      suggested that the activation energy for diffusion and the distribution profile
      of the involved nuclides could become powerful parameters in understanding the
      diffusion mechanism.

PMID- 11288571
TI  - Attempt to model laboratory-scale diffusion and retardation data.
AB  - Different approaches for measuring the interaction between radionuclides and rock
      matrix are needed to test the compatibility of experimental retardation
      parameters and transport models used in assessing the safety of the underground
      repositories for the spent nuclear fuel. In this work, the retardation of sodium,
      calcium and strontium was studied on mica gneiss, unaltered, moderately altered
      and strongly altered tonalite using dynamic fracture column method. In-diffusion
      of calcium into rock cubes was determined to predict retardation in columns. In
      diffusion of calcium into moderately and strongly altered tonalite was
      interpreted using a numerical code FTRANS. The code was able to interprete in
      diffusion of weakly sorbing calcium into the saturated porous matrix. Elution
      curves of calcium for the moderately and strongly altered tonalite fracture
      columns were explained adequately using FTRANS code and parameters obtained from
      in-diffusion calculations. In this paper, mass distribution ratio values of
      sodium, calcium and strontium for intact rock are compared to values, previously
      obtained for crushed rock from batch and crushed rock column experiments. Kd
      values obtained from fracture column experiments were one order of magnitude
      lower than Kd values from batch experiments.

PMID- 11288573
TI  - Diffusion mechanism of chloride ions in sodium montmorillonite.
AB  - For safety assessment of geological disposal of HLW, it is necessary to
      understand the diffusion mechanism of radionuclides in compacted bentonite. In
      this study, the diffusion behavior of chloride ions in compacted montmorillonite
      was studied from the viewpoints of the activation energy for apparent diffusion
      and the basal spacing of the compacted montmorillonite. A unique change in the
      activation energy as a function of the dry density of the montmorillonite was
      found. The activation energy decreased from 17.4 to 13.5 kJ mol-1 as the dry
      density increased from 0.7 to 1.0 Mg m-3 and increased to 25.1 kJ mol-1 at dry
      densities above 1.0 Mg m-3. The basal spacing of 1.88 nm, corresponding to the
      three-water layer hydrate state, was not observed by X-ray diffraction (XRD)
      until the dry density increased to 1.0 Mg m-3, where the minimum activation
      energy was obtained. On the other hand, a basal spacing of 1.56 nm, corresponding
      to the two-water layer hydrate state, was observed at the dry densities of 1.4 Mg
      m-3 and above, where the activation energies were more than 22 kJ mol-1. These
      experimental results suggest that there are at least two additional diffusion
      processes that can raise or reduce the activation energy and are affected by
      water in the region adjacent to the montmorillonite surfaces. If the "Grahame
      model" can be introduced to describe the electrical double layer, surface
      diffusion will be considered the possible predominant diffusion process, even for
      anions like chloride ions.

PMID- 11288574
TI  - Experimental and modeling studies on sorption and diffusion of radium in
      bentonite.
AB  - The sorption and desorption behavior of radium on bentonite and purified smectite
      was investigated as a function of pH, ionic strength and liquid to solid ratio by
      batch experiments. The distribution coefficients (Kd) were in the range of 10(2)
      to > 10(4) ml g-1 and depended on ionic strength and pH. Most of sorbed Ra was
      desorbed by 1 M KCl. The results for purified smectite indicated that Ra sorption
      is dominated by ion exchange at layer sites of smectite, and surface complexation
      at edge sites may increase Ra sorption at higher pH region. Reaction parameters
      between Ra and smectite were determined based on an interaction model between
      smectite and groundwater. The reaction parameters were then used to explain the
      results of bentonite by considering dissolution and precipitation of minerals and
      soluble impurities. The dependencies of experimental Kd values on pH, ionic
      strength and liquid to solid ratio were qualitatively explained by the model. The
      modeling result for bentonite indicated that sorption of Ra on bentonite is
      dominated by ion exchange with smectite. The observed pH dependency was caused by
      changes of Ca concentration arising from dissolution and precipitation of
      calcite. Diffusion behavior of Ra in bentonite was also investigated as a
      function of dry density and ionic strength. The apparent diffusion coefficients
      (Da) obtained in compacted bentonite were in the range of 1.1 x 10(-11) to 2.2 x
      10(-12) m2 s-1 and decreased with increasing in dry density and ionic strength.
      The Kd values obtained by measured effective diffusion coefficient (De) and
      modeled De were consistent with those by the sorption model in a deviation within
      one order of magnitude.

PMID- 11288575
TI  - U-series disequilibria in a groundwater flow route as an indicator of uranium
      migration processes.
AB  - U-series data relating to groundwater, fracture coatings and the adjoining rock
      matrix in a groundwater flow system at the Palmottu natural analogue site was
      examined. The aim was to obtain an experimental reference for migration modelling
      in a transport section defined within the flow system. The U-series reference
      obtained turned out to be a very useful tool for fine tuning the flow route and
      for migration mechanism considerations. The U-series data are well in line with
      other interpretations of the migration system.

PMID- 11288576
TI  - Laboratory migration experiments with radionuclides and natural colloids in a
      granite fracture.
AB  - Natural colloids in groundwater could facilitate radionuclide transport, provided
      the colloids are mobile, are present in sufficient concentrations and can adsorb
      radionuclides. This paper describes the results of a laboratory migration study
      carried out with combinations of radionuclides and natural colloids within a
      fracture in a large granite block to experimentally determine the impact of
      colloids on radionuclide transport. The 85Sr used in this study is an example of
      a moderately sorbing radionuclide, while the 241Am is typical of a strongly
      sorbed radionuclide with very low solubility. The natural colloids used in this
      study were isolated from granite groundwater from Atomic Energy of Canada (AECL)
      Underground Research Laboratory (URL), and consisted of mostly 1-10 nm organic
      colloids, along with lesser amounts of 10-450 nm colloids (organics and
      aluminosilicates). The measured coefficients for radionuclide sorption onto these
      colloids were between 3 x 10(2) and 1 x 10(3) ml/g for 85Sr, and between 7 x
      10(4) and 7 x 10(5) mg/l for 241Am. The 85Sr sorption on the natural colloids
      appeared to be reversible. Migration experiments in the granite block were
      carried out by establishing a flow field between two boreholes (out of a total of
      nine) intersecting a main horizontal fracture. These experiments showed that
      dissolved 85Sr behaved as a moderately sorbing tracer, while dissolved 241Am was
      completely adsorbed by the fracture surfaces and showed no evidence of transport.
      However, when natural colloids were injected together with dissolved 241Am, a
      small amount of 241Am transport was observed, demonstrating the ability of
      natural colloids to facilitate the transport of radionuclides with low
      solubility. Natural colloids had only a minor effect on the transport of 85Sr. In
      a separate experiment to test the effect of higher colloid concentrations on 85Sr
      migration, synthetic colloids were produced from Avonlea bentonite. The
      introduction of a relatively high concentration of bentonite colloids actually
      reduced 85Sr transport because, compared to natural colloids, the bentonite
      colloids were less mobile and they sorbed 85Sr more strongly.

PMID- 11288577
TI  - Comparison of two micro-analytical methods for detecting the spatial distribution
      of sorbed Pu on geologic materials.
AB  - Subsurface transport of groundwater contaminants is greatly influenced by
      chemical speciation, precipitation and sorption processes at the mineral-water
      interface. The retardation of contaminants is often greatest at boundaries
      between minerals and in fractures and pore spaces. The investigation of the
      spatial distribution of sorbed contaminants along these boundaries requires micro
      analytical techniques. The sorption of dissolved Pu(V) on a natural zeolitic tuff
      from Yucca Mountain (NV, USA) was examined using microautoradiography (MAR), X
      ray diffraction (XRD), electron microprobe (EM) techniques, and synchrotron-based
      micro-X-ray fluorescence (micro-SXRF). The tuff contained a heterogeneous
      distribution of zeolites and trace quantities of smectites, Fe oxides (hematite),
      and Mn oxides (rancieite), which are present as fracture fill and pore space
      materials. Micro-SXRF studies showed that Pu is mostly associated with bodies of
      smectite plus Mn oxides, which were typically elevated in Ce, Ga, Nb, Pb, Y, Ca,
      Ti, and Zn. Sorbed Pu was not associated with Fe-rich bodies, which were enriched
      in Cl and Rb. Results of the MAR studies were complementary to that of the micro
      SXRF studies in that Pu was associated with similar elements in the tuff.
      Indirect detection of Pu by EM or micro-SXRF (by analyzing Ag developed on the
      MAR photoemulsion) was a more sensitive method for detecting lower levels of
      sorbed Pu than the direct detection of sorbed Pu via micro-SXRF in the absence of
      the photoemulsion.

PMID- 11288578
TI  - Sorption behavior of U(VI) on phyllite: experiments and modeling.
AB  - The sorption of U(VI) onto low-grade metamorphic rock phyllite was modeled with
      the diffuse double layer model (DDLM) using the primary mineralogical
      constituents of phyllite, i.e. quartz, chlorite, muscovite, and albite, as input
      components, and as additional component, the poorly ordered Fe oxide hydroxide
      mineral, ferrihydrite. Ferrihydrite forms during the batch sorption experiment as
      a weathering product of chlorite. In this process, Fe(II), leached from the
      chlorite, oxidizes to Fe(III), hydrolyses and precipitates as ferrihydrite. The
      formation of ferrihydrite during the batch sorption experiment was identified by
      Mossbauer spectroscopy, showing a 2.8% increase of Fe(III) in the phyllite
      powder. The ferrihydrite was present as Fe nanoparticles or agglomerates with
      diameters ranging from 6 to 25 nm, with indications for even smaller particles.
      These Fe colloids were detected in centrifugation experiments of a ground
      phyllite suspension using various centrifugal forces. The basis for the
      successful interpretation of the experimental sorption data of uranyl(VI) on
      phyllite were: (1) the determination of surface complex formation constants of
      uranyl with quartz, chlorite, muscovite, albite, and ferrihydrite in individual
      batch sorption experiments, (2) the determination of surface acidity constants of
      quartz, chlorite, muscovite, and albite obtained from separate acid-base
      titration, (3) the determination of surface site densities of quartz, chlorite,
      muscovite, and albite evaluated independently of each other with adsorption
      isotherms, and (4) the quantification of the secondary phase ferrihydrite, which
      formed during the batch sorption experiments with phyllite. The surface complex
      formation constants and the protolysis constants were optimized by using the
      experimentally obtained data sets and the computer code FITEQL. Surface site
      densities were evaluated from adsorption isotherms at pH 6.5. The uranyl(VI)
      sorption onto phyllite was accurately modeled with these newly determined
      constants and parameters of the main mineralogical constituents of phyllite and
      the secondary mineralization phase ferrihydrite. The modeling indicated that
      uranyl sorption to ferrihydrite clearly dominates uranyl sorption, showing the
      great importance of secondary iron phases for sorption studies.

PMID- 11288579
TI  - Reactive barriers for 137Cs retention.
AB  - 137Cs was dispersed globally by cold war activities and, more recently, by the
      Chernobyl accident. Engineered extraction of 137Cs from soils and groundwaters is
      exceedingly difficult. Because the half-life of 137Cs is only 30.2 years,
      remediation might be more effective (and less costly) if 137Cs bioavailability
      could be demonstrably limited for even a few decades by use of a reactive
      barrier. Essentially permanent isolation must be demonstrated in those few
      settings where high nuclear level wastes contaminated the environment with 135Cs
      (half-life 2.3 x 10(6) years) in addition to 137Cs. Clays are potentially a low
      cost barrier to Cs movement, though their long-term effectiveness remains
      untested. To identify optimal clays for Cs retention, Cs desorption was measured
      for five common clays: Wyoming Montmorillonite (SWy-1), Georgia Kaolinites (KGa-1
      and KGa-2), Fithian Illite (F-Ill), and K-Metabentonite (K-Mbt). Exchange sites
      were pre-saturated with 0.16 M CsCl for 14 days and readily exchangeable Cs was
      removed by a series of LiNO3 and LiCl washes. Washed clays were then placed into
      dialysis bags and the Cs release to the deionized water outside the bags
      measured. Release rates from 75 to 139 days for SWy-1, K-Mbt and F-Ill were
      similar; 0.017% to 0.021% sorbed Cs released per day. Both kaolinites released Cs
      more rapidly (0.12% to 0.05% of the sorbed Cs per day). In a second set of
      experiments, clays were Cs-doped for 110 days and subjected to an extreme and
      prolonged rinsing process. All the clays exhibited some capacity for irreversible
      Cs uptake. However, the residual loading was greatest on K-Mbt (approximately
      0.33 wt.% Cs). Thus, this clay would be the optimal material for constructing
      artifical reactive barriers.

PMID- 11288580
TI  - UraniumVI sorption behavior on silicate mineral mixtures.
AB  - UraniumVI sorption experiments involving quartz and clinoptilolite, important
      mineral phases at the proposed US nuclear waste repository at Yucca Mountain, NV,
      were conducted to evaluate the ability of surface complexation models to predict
      UVI sorption onto mineral mixtures based on parameters derived from single
      mineral experiments. The experiments were conducted at an initial UVI aqueous
      concentration of approximately 2.0 x 10(-7) mol.l-1 (0.1 mol.l-1 NaNO3 matrix)
      and over the pH range approximately 2.5 to approximately 9.5. The UVI solutions
      were reacted with either quartz or clinoptilolite only, or with mixtures of the
      two minerals. The experiments were carried out under atmospheric pCO2(g)
      conditions (in loosely capped containers) or under limited pCO2(g) (in capped
      containers or in a glove box). Data from sorption experiments on quartz at
      atmospheric pCO2 conditions were used to derive UVI binding constants for a
      diffuse-layer surface complexation model (DLM). The DLM was then used with
      surface area as a scaling factor to predict sorption of UVI onto clinoptilolite
      and clinoptilolite/quartz mixtures under both atmospheric and low pCO2
      conditions. The calculations reproduced many aspects of the pH-dependent sorption
      behavior. If this approach can be demonstrated for natural mineral assemblages,
      it may be useful as a relatively simple method for improving radionuclide
      transport models in performance-assessment calculations.

PMID- 11288581
TI  - Retardation capacity of organophilic bentonite for anionic fission products.
AB  - Sorption and diffusivity of iodide and pertechnetate (I- and TcO4-) on MX-80
      bentonite with different hexadecylpyridinium (HDPy+) loadings were studied using
      equilibrium solutions of different ionic strengths. In HDPy(+)-modified
      bentonite, iodide and pertechnetate ions exhibited increasing sorption
      (characterized by the distribution ratio, Rd), while Cs+ and Sr2+ showed
      decreasing sorption with increasing organophilicity. In case of medium-loading
      levels, the simultaneous sorption of anions (I- and TcO4-) and cations (Cs+ and
      Sr2+) was observed. Sorption of ions was influenced by the composition of the
      electrolytes employed. It decreased gradually with increasing ionic strength of
      the electrolyte solutions. The experiments revealed the general tendency that the
      diffusivity (Da [cm2.s-1]) for iodide and pertechnetate decreases with increasing
      organophilicity and increases with increasing ionic strength of the equilibrium
      solutions, confirming the results of the sorption experiments. Additionally, some
      mineralogical and chemical investigations, like IR spectral analysis of the
      organo-bentonite samples and exchange behavior of HDPy+, were performed. On the
      basis of these analyses, it was concluded that the alkylammonium ions are sorbed
      as (1) HDPy+ cations, (2) HDPyCl molecules and (3) micelles with decreasing
      binding intensities in this order.

PMID- 11288582
TI  - Present state and future directions of modeling of geochemistry in
      hydrogeological systems.
AB  - A first step towards understanding and controlling the fate and dissemination of
      radioactive waste is to create a concise and comprehensive theoretical framework
      for the rather non-linear processes involved--hence, the need for geochemical
      models. Two classes of geochemical models are commonly used, i.e., static and
      hydrodynamic models. In contrast to static models, hydrodynamic models combine
      geochemical reactions with hydrogeological processes such as ground-water flow,
      diffusion and dispersion. In this review, we examine the present state of
      geochemical models in terms of included processes, thermodynamic databases,
      missing phenomena, numerical behavior and performance. It is shown that over the
      past decade, significant progress has been made with respect to modeling of
      geochemistry in hydrodynamic systems: this is illustrated by describing several
      applications. Finally, we focus on the perspectives of geochemical modeling in
      the assessment of the safety of nuclear waste disposal.

PMID- 11288583
TI  - An integrated sorption-diffusion model for the calculation of consistent
      distribution and diffusion coefficients in compacted bentonite.
AB  - A thermodynamic sorption model and a diffusion model based on electric double
      layer (EDL) theory are integrated to yield a surface chemical model that treats
      porewater chemistry, surface reactions, and the influence of charged pore walls
      on diffusing ions in a consistent fashion. The relative contribution of Stern and
      diffuse layer to the compensation of the permanent surface charge represents a
      key parameter; it is optimized for the diffusion of Cs in Kunipia-F bentonite, at
      a dry density of 400 kg/m3. The model is then directly used to predict apparent
      diffusivities (Da) of Cs, Sr, Cl-, I- and TcO4- and corresponding distribution
      coefficients (Kd) of Cs and Sr in different bentonites as a function of dry
      density, without any further adjustment of surface chemical and EDL parameters.
      Effective diffusivities (De) for Cs, HTO, and TcO4- are also calculated. All
      calculated values (Da, De, Kd) are fully consistent with each other. A comparison
      with published, measured data shows that the present model allows a good
      prediction and consistent explanation of (i) apparent and effective diffusivities
      for cations, anions, and neutral species in compacted bentonite, and of (ii) Kd
      values in batch and compacted systems.

PMID- 11288584
TI  - Kinetic modeling of microbially-driven redox chemistry of radionuclides in
      subsurface environments: coupling transport, microbial metabolism and
      geochemistry.
AB  - Microbial reactions play an important role in regulating pore water chemistry as
      well as secondary mineral distribution in many subsurface systems and, therefore,
      may directly impact radionuclide migration in those systems. This paper presents
      a general modeling approach to couple microbial metabolism, redox chemistry, and
      radionuclide transport in a subsurface environment. To account for the likely
      achievement of quasi-steady state biomass accumulations in subsurface
      environments, a modification to the traditional microbial growth kinetic equation
      is proposed. The conditions for using biogeochemical models with or without an
      explicit representation of biomass growth are clarified. Based on the general
      approach proposed in this paper, the couplings of uranium reactions with
      biogeochemical processes are incorporated into computer code BIORXNTRN Version
      2.0. The code is then used to simulate a subsurface contaminant migration
      scenario, in which a water flow containing both uranium and a complexing organic
      ligand is recharged into an oxic carbonate aquifer. The model simulation shows
      that Mn and Fe oxyhydroxides may vary significantly along a flow path. The
      simulation also shows that uranium(VI) can be reduced and therefore immobilized
      in the anoxic zone created by microbial degradation.

PMID- 11288585
TI  - Numerical modeling of humic colloid borne americium (III) migration in column
      experiments using the transport/speciation code K1D and the KICAM model.
AB  - The humic colloid borne Am(III) transport was investigated in column experiments
      for Gorleben groundwater/sand systems. It was found that the interaction of Am
      with humic colloids is kinetically controlled, which strongly influences the
      migration behavior of Am(III). These kinetic effects have to be taken into
      account for transport/speciation modeling. The kinetically controlled
      availability model (KICAM) was developed to describe actinide sorption and
      transport in laboratory batch and column experiments. Application of the KICAM
      requires a chemical transport/speciation code, which simultaneously models both
      kinetically controlled processes and equilibrium reactions. Therefore, the code
      K1D was developed as a flexible research code that allows the inclusion of
      kinetic data in addition to transport features and chemical equilibrium. This
      paper presents the verification of K1D and its application to model column
      experiments investigating unimpeded humic colloid borne Am migration. Parmeters
      for reactive transport simulations were determined for a Gorleben groundwater
      system of high humic colloid concentration (GoHy 2227). A single set of
      parameters was used to model a series of column experiments. Model results
      correspond well to experimental data for the unretarded humic borne Am
      breakthrough.

PMID- 11288586
TI  - Modeling colloid transport for performance assessment.
AB  - The natural system is expected to contribute to isolation at the proposed high
      level nuclear waste (HLW) geologic repository at Yucca Mountain, NV (YM). In
      developing performance assessment (PA) computer models to simulate long-term
      behavior at YM, colloidal transport of radionuclides has been proposed as a
      critical factor because of the possible reduced interaction with the geologic
      media. Site-specific information on the chemistry and natural colloid
      concentration of saturated zone groundwaters in the vicinity of YM is combined
      with a surface complexation sorption model to evaluate the impact of natural
      colloids on calculated retardation factors (RF) for several radioelements of
      concern in PA. Inclusion of colloids into the conceptual model can reduce the
      calculated effective retardation significantly. Strongly sorbed radionuclides
      such as americium and thorium are most affected by pseudocolloid formation and
      transport, with a potential reduction in RF of several orders of magnitude.
      Radioelements that are less strongly sorbed under YM conditions, such as uranium
      and neptunium, are not affected significantly by colloid transport, and transport
      of plutonium in the valence state is only moderately enhanced. Model results
      showed no increase in the peak mean annual total effective dose equivalent (TEDE)
      within a compliance period of 10,000 years, although this is strongly dependent
      on container life in the base case scenario. At longer times, simulated container
      failures increase and the TEDE from the colloidal models increased by a factor of
      60 from the base case. By using mechanistic models and sensitivity analyses to
      determine what parameters and transport processes affect the TEDE, colloidal
      transport in future versions of the TPA code can be represented more accurately.

PMID- 11288587
TI  - Development and testing of radionuclide transport models for fractured rock:
      examples from the Nagra/JNC Radionuclide Migration Programme in the Grimsel Test
      Site, Switzerland.
AB  - The joint Swiss National Co-operative for the Disposal of Radioactive Waste
      (Nagra)/Japan Nuclear Cycle Development Institute (JNC) Radionuclide Migration
      Programme has now been on-going for over a decade in Nagra's Grimsel Test Site
      (GTS). The main aim of the programme has been the direct testing of radionuclide
      transport models in as realistic manner as possible. Although it will never be
      possible to fully test these models due to the large time and distance scales
      involved, tests of the model assumptions in scaled down but otherwise realistic
      conditions will contribute to developing confidence in the predictive power of
      the models. In this paper, the Nagra/JNC approach is highlighted with examples
      from a large programme of field, laboratory and natural analogue studies based
      around the GTS. The successes and failures are discussed as in the general
      approach to the thorough testing of predictive transport codes which will be used
      in repository performance assessment (PA). Some of the work is still on-going and
      this represents the first presentation of a unique set of results and
      conclusions.

PMID- 11288588
TI  - Radionuclide release and transport from nuclear underground tests performed at
      Mururoa and Fangataufa--predictions under uncertainty.
AB  - In the context of a study by the International Geomechanical Commission (IGC) and
      the International Atomic Energy Agency (IAEA) on the effects of nuclear tests at
      the atolls of Mururoa and Fangataufa, release to the biosphere is estimated for
      35 radionuclides originating from 147 nuclear underground tests. Based on a
      qualitatively characterised hydrogeological situation of atolls and relatively
      scarce site-specific data, a model chain was developed to conservatively estimate
      the radionuclide fluxes via groundwater, from their sources, the explosion
      cavities, towards the biosphere, the ocean or lagoon. Finite element hydro
      thermal modelling was used to describe water flow. Parameters were calibrated by
      a very few measured pre-test temperature profiles in bore holes. The impact of
      the tests on groundwater flow and mechanical impact on rock was considered.
      Estimates were made to quantify spatial extensions and temporal evolution of
      impact by using measurements on refilling rate of the cavities. Tests were
      categorised according to their specific yield and location although detailed data
      were missing. A base case parameter set was defined for the hydraulic conditions
      and for the initial radionuclide inventory of individual tests. Models were used
      to describe the concentration of radionuclides in the cavities as a function of
      time. Radionuclide transport from the cavities to the biosphere was represented
      by two different approaches: a double porosity model for the fractured volcanic
      rock and a single porosity model for the overlaying, highly porous carbonates.
      Results consist of conservative estimates on radionuclide release into the
      environment, or concentration in the lagoon or ocean water. Their sensitivity was
      investigated using different models and parameters. A few measured data
      (concentrations in a few cavities, in the deep carbonates and in the lagoons for
      selected radionuclides, such as 3H, 14C, 36Cl, 90Sr, 129I, 137Cs239 240Pu and
      241Am) were available for a comparison with the calculations. In view of the lack
      and uncertainty of site-specific data, the agreement is of acceptable quality.

PMID- 11288589
TI  - Heterogeneous matrix diffusion in crystalline rock--implications for geosphere
      retardation of migrating radionuclides.
AB  - As a basis for an analysis of the effect of rock heterogeneity on radionuclide
      migration in a single fracture, the geostatistics of the main properties
      governing solute transport in crystalline rock have been determined
      experimentally for two granitic rock types. The rock samples were collected at
      the Aspo Hard Rock Laboratory, Sweden and used to deduce the auto-covariance
      functions for the porosity, effective diffusivity and partition coefficient, kd,
      and adsorption kinetics. One-dimensional analytical solutions for the mean values
      of the temporal moments of the residence time probability density function (PDF)
      show that the heterogeneity of the rock properties can have a substantial impact
      on the transport. A case study of the effect of heterogeneity in matrix diffusion
      for a single fracture could be performed by decomposing the transport problem
      into a one-dimensional mass transfer problem and a two-dimensional flow problem
      using a Lagrangian method of description. Monte Carlo simulations of the flow
      field indicate that the correlation length of the aperture is much longer along
      the trajectory paths than along an arbitrary direction. Increasing the
      correlation lengths and variances of the aperture and matrix diffusion increases
      significantly the variance of the travel time PDF.

PMID- 11288590
TI  - Numerical modeling of coupled variably saturated fluid flow and reactive
      transport with fast and slow chemical reactions.
AB  - The couplings among chemical reaction rates, advective and diffusive transport in
      fractured media or soils, and changes in hydraulic properties due to
      precipitation and dissolution within fractures and in rock matrix are important
      for both nuclear waste disposal and remediation of contaminated sites. This paper
      describes the development and application of LEHGC2.0, a mechanistically based
      numerical model for simulation of coupled fluid flow and reactive chemical
      transport, including both fast and slow reactions in variably saturated media.
      Theoretical bases and numerical implementations are summarized, and two example
      problems are demonstrated. The first example deals with the effect of
      precipitation/dissolution on fluid flow and matrix diffusion in a two-dimensional
      fractured media. Because of the precipitation and decreased diffusion of solute
      from the fracture into the matrix, retardation in the fractured medium is not as
      large as the case wherein interactions between chemical reactions and transport
      are not considered. The second example focuses on a complicated but realistic
      advective-dispersive-reactive transport problem. This example exemplifies the
      need for innovative numerical algorithms to solve problems involving stiff
      geochemical reactions.

PMID- 11288591
TI  - [Orphan drugs].
AB  - The paper discusses the problems of orphan drugs from the standpoint of the
      attitude of state authorities in the USA, Japan, and particularly Europe (the
      European Union) to their definition and the formation of appropriate legislation-
      financial provision for the development, production, provision of exclusive sale
      rights--which warranties the availability of the drug to every patient suffering
      from a rare disease.

PMID- 11288592
TI  - ["Silymarin"--an extract from the milk thistle (Silybum marianum)--is it a drug
      or nutritional supplement?].
AB  - Thanks to the new knowledge, there is an increase of interest in plant extracts
      in the developed countries, but their classification is, however, problematic. It
      is necessary to clearly define the borderline between a drug or a defined content
      of an individual active principle, and a nutritional supplement, which is freely
      on sale. The extract from the seeds of S. marianum of (ESM) shows biological
      effects corresponding to nutritional supplements, and it is therefore more
      logical to class ESM with this group and to investigate the pharmacological
      effects in its chemically defined components.

PMID- 11288593
TI  - [Viral liver diseases. Current status of therapy] ].
AB  - Viral liver diseases, particularly hepatitides of type B (HBV) and C (HCV) show
      an increasing trend, the number of infected people in the world being several
      hundred million people. With the exception of other forms (HAV, HDV, HEV, and
      HGV), where infectivity is also high, possible transmission and infection in HBV
      and HCV are often independent of the affected person (blood transfusion,
      stomatological operations, surgery, etc.). Treatment of hepatitides not
      proceeding into a chronic stage is without any problems at the moment. In the
      case of HBV, besides chemical drugs which are being developed, vaccination is
      available. Hepatitis C remains to be a problem of world importance. Its growth in
      recent years runs parallel to an increase in drug addicts and HIV infection. The
      difficulties in the development of vaccines are related to rapid mutation of the
      virus and continuous formation of other serotypes. Progress in many biological
      disciplines is a certain warranty that the so-called NS3 proteases inhibitors and
      medicaments of other types, including vaccines, will be introduced into practice
      for HCV treatment.

PMID- 11288594
TI  - [Coenzyme Q and its therapeutic use].
AB  - Coenzyme Q (CoQ), a lipophilic substituted benzoquinone, is present in all animal
      and plant cells. It is endogenously synthesised in tissues and involved in a
      variety of cellular processes. It is well documented that CoQ is an obligatory
      component of the respiratory chain in the inner mitochondrial membrane coupled to
      ATP synthesis. However, its additional localisation in different subcellular
      fractions is probably associated with its multiple functions in the cell (as a
      part of extramitochondrial electron transport chains, a powerful antioxidant
      agent or a membrane stabiliser). The actions outlined for CoQ can explain its
      broad range of therapeutic effects. This presentation is a brief review of recent
      knowledge concerning medical aspects of CoQ in mammals. The energetic role seems
      sufficient to explain at least some of the clinical effects (heart failure,
      neurodegenerative diseases) but in other cases the antioxidant function may be a
      more convenient explanation. Nevertheless, a better knowledge of CoQ functions at
      the molecular level and additional well-designed studies are required to provide
      specific recommendation and definitive evidence of its therapeutic effects.

PMID- 11288595
TI  - [Bergenia crassifolia (L.) Fritsch in vitro].
AB  - Sterile germinating plants were used to derive a tissue culture. The greatest
      stimulating effect on the growth of the culture was exerted by NAA cultures in
      all concentrations tested, by IAA in concentrations of 1.0 and 10.0 mg.l-1, by
      IBA in a concentration of 0.1 mg.l-1, and by the combination of IBA + K. The
      difference between the values of growth on these media was statistically
      insignificant. TLC analysis of callus extracts demonstrated the presence of
      bergenin, arbutin, hydroquinone, and methylarbutine. HPLC analysis confirmed the
      findings (arbutin 0.25%, hydroquinone 0.05%, methylarbutin 0.28%). The results of
      biotransformation tests show that the highest increase in arbutin took place
      after addition of 4-hydroxybenzoic acid and withdrawal of the sample after 24
      hours (3.82%). No transformation of arbutin or 4-methoxyphenol to produce
      methylarbutin took place in the culture under the given conditions. The highest
      increase in the summary content of phenolic substances occurred with the use of
      the elicitor Pseudomonas aeruginosa--88% (conc. 0.0001 g/100 ml, 12-hour action).

PMID- 11288596
TI  - [Hydrolysis kinetics of stobadine acyl-derivatives, the prodrug forms of free
      oxygen radical extinguishers. Part 3. Hydrolysis in a neutral medium].
AB  - The pyridoindole derivative stobadin, [(-)-cis-2,8-dimetyl-2,3,4,4a,5,9b
      hexahydro-1H-pyrido[4,3b]-indole] is a perspective antiarrhythmic, antihistamine,
      anaesthetic, antiulcerous drug capable of extinguishing free oxygen radical. Its
      prodrug forms--N(5)- acyl-substituted stobadine--of the active substance-
      stobadine--have been prepared and it is assumed that the will be hydrolyzed in
      the organism and the active substance will be released in higher concentrations
      in different biological tissues. The present paper is concerned with the
      investigation of the kinetics of the hydrolysis of 13 acyl derivatives of
      stobadine in the medium of a buffer solution of pH 7 at temperatures of 70
      degrees C and 75 degrees C spectrophotometrically in the UV region of the
      spectrum. The determined rate constants were correlated with the length of the
      side acyl chain and the pKa values of the drugs under study. The profile of log k
      -pH of substances was determined.

PMID- 11288597
TI  - [The firmness of Avicel PH 102 and Avicel PH 301 compression and the effect of
      magnesium stearate] ].
AB  - The paper evaluated the strength of compacts made of microcrystalline cellulose
      of two types used as dry binders in the technology of direct compression of
      tablets, i.e. Avicel PH 102 and Avicel PH 301. The effect of three concentrations
      of the lubricant magnesium stearate (0.4; 0.8; 1.2%) on the strength of tablets
      made from these substances was also evaluated. Tables were compressed using three
      forces of compression (3; 3.5, and 4 kN). On the basis of the obtained results it
      can be concluded that Avicel PH 102 provides, under identical forces of
      compression, stronger compacts than Avicel PH 301 does. It has been further found
      that a magnesium stearate concentration of 0.4 markedly decreases the tensile
      strength of Avicel PH 102 tablets, and another marked decrease is observed with a
      concentration of 1.2%. The decrease in the tensile strength of Avicel PH 301
      compacts due to magnesium stearate is not so marked as in Avicel PH 102 tablets,
      and with stearate concentrations of 0.4% and 1.2% the difference in strength is
      not of such importance in comparison with the previous concentrations.

PMID- 11288598
TI  - [Relations between pharmacies and drug stores during the first years of
      Czechoslovak independence].
AB  - Union of chemists exploited the disputes between pharmacists and legislators for
      its own prosperity. In 1780 the sale of natural drugs was permitted to the
      chemists for first time and the Trade Rules of 1856 (later amended) gave them a
      possibility of production, preparation and sale of poisons and medicaments,
      unless they were reserved for pharmacists only (section 15, article 14). Among
      the first founders of chemist's shops belonged the pharmacists who could not
      establish their own pharmaceutical store due to lack of finance or complaints
      from their colleagues. The chemist's didn't have to fulfill the obligatory
      requirements for rooms and equipment, they were not regularly checked and they
      had less expenses and also lower prices. Their lower profit from the sale of
      medicaments was compensated by selling typical chemist's articles. The
      pharmacists brought the level of chemists nearly to the level of organized
      pharmacy (pharmaceutics supervisory committee, division into regions, a two-years
      special school, producing and purchasing cooperatives). However, around 1925 the
      pharmacists became aliens from the point of view of chemists. The chemists felt
      their own existence threatened and tried to refuse pharmaceutical studies as an
      approval for chemist trade and tried to limit the sale of cosmetics and dietetics
      in the pharmaceutical stores. Without bashfulness, they themselves dispatched and
      prepared medicaments on medical and veterinary prescriptions even though it was
      illegal. Later they tried to legalize this state during the discussions of the
      reform of pharmaceutical law. Protesting pharmacists did not have efficient
      support either from the pharmaceutics supervisory committee, Ministry of Health
      Care, or Chamber of Commerce. The state solution to this problem which lacked any
      concept, and together with inconsistency and disunity among pharmacists
      themselves contributed to deepen the problems between pharmacists and chemists.
      Unfortunately, pharmacists often focused on minor matters and omitted the
      essential problems of their profession.

PMID- 11288599
TI  - The comparative assessment of the healing process of the intestinal anastomoses
      in dependence of different materials: an experimental study.

PMID- 11288600
TI  - Resorption and calcification of chemically modified collagen/hyaluronan hybrid
      membranes.
AB  - The objectives of this study were to characterize collagen/hyaluronan hybrid
      membrane before and after different chemical crosslinking, as well as to
      investigate the impact of the treatment method on resorption and calcification
      processes by in vivo tests. The kinetics study of resorption of
      collagen/hyaluronan membranes showed that after 28 days the membranes were
      completely resorbed. The modification of the membranes with glutaraldehyde
      comparing to the similar modification of pericardial tissue conducts higher
      calcification. Treatment with hexamethylene diisocyanate together with
      poly(oxyethylene) improved mechanical properties but the resorption process was
      similar. Additional treatments with diphenylphosphorylazide and 1-ethyl-3-(3
      dimethylamino-propyl) carbodiimide (EDAC) resulted in prolongation of the
      resorption time. Calcification was suppressed in case of treatment with EDAC.

PMID- 11288601
TI  - Endovascular occlusion of branches of hepatic artery with poly(2-hydroxyethyl
      methacrylate) emboli as a single occlusive measure in hepatology.

PMID- 11288602
TI  - [Biocompatibility assessment of aqueous extracts from new multiblock poly(ester
      ester) copolymer].
AB  - In the Technical University of Szczecin, Department of Chemical Fibres and
      Physical Chemistry of Polymer there has been synthesised a new polymer based on
      butylene terephthalate--PBT and dimerized fatty acid--DFA. Five different
      polymers varying in mechanical properties depending on hard segments--PBT and
      soft segments--DFA composition were obtained. Assessment of biocompatibility of
      the new materials was conducted according to FDP. Prepared water extracts from
      polymers were applicated intravenously to mouse and intra-abdominaly to mice and
      guinea pigs. All animals survived spell of the experiment and no signs of
      physical degradation were noticed. Kidney, liver, spleen, heart and peritoneum
      specimens was taken and evaluated microscopically. There was no signs of toxic
      action of the extracts. Based on principles in FDP and the data from animal
      studies it is applicable that evaluated materials have no increased toxicity.

PMID- 11288603
TI  - Evaluation of the healing process after implantation of synthetic material called
      Tegmentum consisting of polyester mesh covered with polyurethane in rat
      peritoneum.
AB  - Polyester meshes are one of the synthetic prosthetic materials widely applied for
      the reconstruction of abdominal layers in child and neonatal surgery,
      cardiosurgery or vascular surgery. Because of the lack or insufficiency of the
      own, natural material multiple researches are performed in order to find the best
      material able to replace natural tissue. The most suitable prosthesis ought to
      be: sterile, non-toxic, soft, flexible, elastic, not very stretchy, durable, easy
      to operate (cutting, suturing); to create desired shape required while
      reconstracting, totally resistant to contagion, without any complication after
      being implanted. Since early seventies many scientists following above
      requirements have carried out researches to create the most similar prosthesis
      morphologically and functionally to human tissue but still there is no such an
      ideal material on the market. Polyester with its derivatives is one of the most
      commonly applied synthetic substances in surgery. The type of biomaterial highly
      depends on its purpose e.g.: for vascular prosthesis materials that are
      resorptive in organism and support tightness (gelatine, albumin, collagen); while
      for temporal replacement abdominal layers with prosthesis the most suitable is
      impervious to systemic fluids bacteria etc material, that prevents penetrating
      the surface of prosthesis by surrounding tissues, adhesions with intestinum or
      other organs. Tegmentum is a material that posses these features. This is a
      polyester mesh covered with polyurethane on one side produced by Tricomed S.A.
      (Lodz). Tegmentum has already been applied to neonates with congenital
      eventration in Child and Neonatal Ward in the "Szpital Pomnik Matki Polki"
      hospital in Lodz.

PMID- 11288604
TI  - Children's body image concerns and eating disturbance: a review of the
      literature.
AB  - In recent years a large number of studies have examined body image concerns, and
      early symptoms of eating disturbance among children. However, to date there has
      been no synthesis or evaluation of these studies. The purpose of the present
      article is to review and evaluate the research that has examined body image
      concerns, and eating attitudes and behaviors among children 6 to 11 years of age.
      The instruments used to assess body image concerns and eating disturbance in
      children closely resemble those used with adolescents and adults. Overall, the
      psychometric data for these instruments are very good and there is sufficient
      evidence indicating that they can be used reliably and validly. In addition,
      similar variables to those studied in adolescent and adult samples have been
      found to be associated with children's body image concerns and early eating
      disturbance. These include gender, age, body mass index, race, sociocultural
      pressures, and self-concept. Our understanding of the development of body image
      concerns and eating disturbance in children is limited, however, by the fact that
      most of the research in this field has been based on cross-sectional data, and
      the studies have focused almost exclusively on weight loss cognitions and
      behaviors.

PMID- 11288605
TI  - The "A-B-C's" of the cluster B's: identifying, understanding, and treating
      cluster B personality disorders.
AB  - This article is a summary of some of the more recent research on the diagnosis,
      etiology, and treatment of Cluster B personality disorders (antisocial,
      histrionic, borderline, and narcissistic). Research on psychological,
      psychosocial, and biological perspectives of these disorders is presented.
      Individual psychotherapy, group psychotherapy, and other forms of multi-person
      therapies are also discussed. Finally, perspectives on issues of
      countertransference when treating these personality-disordered patients are
      addressed.

PMID- 11288606
TI  - A review of psychological factors/processes affecting anxious responding during
      voluntary hyperventilation and inhalations of carbon dioxide-enriched air.
AB  - Despite advances in our understanding of the nature of anxiety-related responding
      during periods of elevated bodily arousal, it is not necessarily evident by what
      psychological mechanisms anxiety is produced and maintained. To address this
      issue, researchers have increasingly employed biological challenge procedures to
      examine how psychological factors affect anxious responding during elevated
      bodily arousal. Of the challenging procedures, hyperventilation and inhalations
      of carbon dioxide-enriched air have been among the most frequently employed, and
      a relatively large body of literature using these procedures has now accumulated.
      Unfortunately, existing reviews do not comprehensively examine findings from
      hyperventilation and inhalations of carbon dioxide studies, and only rarely the
      methodological issues specific to these studies. To address these issues, we
      review the voluntary hyperventilation and carbon dioxide-enriched air literature
      in order to identify the primary methodological issues/limitations of this
      research and address the extent to which psychological variables influence
      anxious responding to such challenges. Overall, we conclude challenge research is
      a promising paradigm to examine the influence of psychological variables in
      anxious responding, and that such work will likely be enhanced with greater
      attention to psychological process issues.

PMID- 11288607
TI  - Comparative effects of short-term psychodynamic psychotherapy and cognitive
      behavioral therapy in depression: a meta-analytic approach.
AB  - This article reviews the efficacy of short-term psychodynamic psychotherapy
      (STPP) in depression compared to cognitive-behavioral therapy (CBT) or behavioral
      therapy (BT). In this review, only studies in which at least 13 therapy sessions
      were performed have been included, and a sufficient number of patients per group
      were treated (N > or = 20). With regard to outcome criteria, the results were
      reviewed for improvements in depressive symptoms, general psychiatric symptoms,
      and social functioning. Six studies met the inclusion criteria. RESULTS: In 58 of
      the 60 comparisons (97%) performed in the six studies and their follow-ups, no
      significant difference could be detected between STPP and CBT/BT concerning the
      effects in depressive symptoms, general psychiatric symptomatology, and social
      functioning. Furthermore, STPP and CBT/BT did not differ significantly with
      regard to the patients that were judged as remitted or improved. According to a
      meta-analytic procedure described by R. Rosenthal (1991) the studies do not
      differ significantly with regard to the patients that were judged as remitted or
      improved after treatment with STPP or CBT/BT. The mean difference between STPP
      and CBT/BT concerning the number of patients that were judged as remitted or
      improved corresponds to a small effect size (post-assessment: phi = 0.08, follow
      up assessment: phi = 0.12). Thus, STPP and CBT/BT seem to be equally effective
      methods in the treatment of depression. However, because of the small number of
      studies which met the inclusion criteria, this result can only be preliminary.
      Furthermore, it applies only to the specific forms of STPP that were examined in
      the selected studies and cannot be generalized to other forms of STPP. Further
      studies are needed to examine the effects of specific forms of STPP in both
      controlled and naturalistic settings. Furthermore, there are findings indicating
      that 16-20 sessions of both STPP and CBT/BT are insufficient for most patients to
      achieve lasting remission. Future studies should address the effects of longer
      treatments of depression.

PMID- 11288608
TI  - Clinical significance: history, application, and current practice.
AB  - The meaningfulness of psychotherapy outcome as measured in therapy research is a
      persistent and important issue. Following a period of emphasis on statistically
      significant findings for treated versus control groups, many researchers are
      renewing efforts to investigate the meaningfulness of individual change. Several
      statistical methods are available to evaluate the meaningfulness of client's
      changes occurring as a result of treatment. This article reviews the history of
      the clinical significance concept; describes the various methods for defining
      improvement, recovery, and clinically significant change; examines current
      criticisms of the methods; and describes the current use of the methods in
      practice.

PMID- 11288609
TI  - Social reasoning: a source of influence on aggression.
AB  - Aggressive children show deficits and biases in their social information
      processing. Cognitions based on early experience and social schemas are also
      related to development and maintenance of aggressive behavior. Social reasoning
      can be linked to these aspects of social cognition, impacting on the situational
      cues individuals encode, their interpretations of events, and influencing
      response decisions. Past experience also influences development of social
      reasoning and social schema. Despite this, current discussion of the links
      between cognition and aggression rarely involves consideration of the influence
      of social reasoning. In this review, domain theory (E. Turiel, 1978, 1983)
      underpins an examination of links between social reasoning and aggression using
      empirical evidence drawn from research on the social reasoning of normal and
      aggressive children. Children as young as 3 appear to use consistent patterns of
      social reasoning when making judgments about transgressions and other social
      events, and these patterns are linked to social reasoning domains. We propose
      that aggressive children access information from the underlying social reasoning
      domains differently than their prosocial peers. This in turn affects their
      decision making and subsequent behavior in social situations. Our review explores
      developmental and clinical implications of the proposal and provides directions
      for future research.

PMID- 11288610
TI  - Interpersonal and family functioning of female survivors of childhood sexual
      abuse.
AB  - The empirical literature that addresses the association between childhood sexual
      abuse (CSA) and the interpersonal functioning of female survivors within their
      adult family context is critically examined. Specifically, research on
      relationship difficulties, problems in attachment, marital conflict and divorce,
      secondary traumatization, sexual dysfunction, maternal attitudes and functioning,
      and the heightened risk for having children who themselves are sexually abused is
      reviewed. There is converging evidence in both clinical and community samples
      that, compared to other women, female CSA survivors do experience more
      relationship problems and more problems in sexual functioning. Based on community
      samples, there is an indication that CSA survivors experience problems in marital
      functioning and attachment. Beyond this, little sound research has addressed the
      issues of secondary traumatization, maternal attitudes, maternal functioning, or
      intergenerational patterns of abuse. The use of specificity designs, improved
      sampling strategies, and standardized, psychometrically strong measures in future
      research would greatly improve the quality of our knowledge on the interpersonal
      and family functioning of CSA survivors.

PMID- 11288611
TI  - From illness narratives to social commentary: a Pirandellian approach to
      "nerves".
AB  - The concept of "nerves" is an integral component of the language of distress
      found in a number of societies. Individuals, however, often extend its meaning
      well beyond the realm of suffering. In this article, I examine some Sicilian
      Canadian uses of "nerves" from a Pirandellian perspective. This, I believe, gives
      us an insight into how people (1) make use of illness narratives to give meaning
      to their life experiences, and (2) attempt to influence the thought and behavior
      of significant others. In the process, I address the question how do we move away
      from anthropological definitions and explanations that tend to simplify or mask
      some of the rich complexities surrounding the meaning(s) of "folk" concepts?

PMID- 11288612
TI  - Toward a political economy of opinion formation on genetically modified foods.

PMID- 11288613
TI  - From risk to globalization: discursive shifts in the French debate about GMOs.

PMID- 11288614
TI  - Health, environment, and transgenic agriculture.

PMID- 11288615
TI  - An MAQ innovation.

PMID- 11288616
TI  - The United States, India, and GM foods.

PMID- 11288617
TI  - Public perceptions of agricultural biotechnology--a nonsocial science
      perspective.

PMID- 11288618
TI  - "New beginnings": a case study in gay men's changing perceptions of quality of
      life during the course of HIV infection.
AB  - This article reports results of an ethnographic study that sought to understand
      how a cohort of gay men living with HIV infection evaluated and worked to
      preserve or improve the quality of their lives. Themes of life story narratives
      are identified, each with an associated stylistic self-orientation to living with
      HIV infection. Changes in thematic content of a selected participant's life story
      narratives are discussed, demonstrating how events of his daily life are
      integrated into the narratives. Resultant concurrent shifting of themes and
      stylistic orientations is linked to his perception of improved quality of life.

PMID- 11288619
TI  - Interpretations of condom use and nonuse among young Norwegian gay men: a
      qualitative study.
AB  - Among the strategies adopted by gay men and the gay community for HIV prevention,
      the promotion of condom use has been pivotal. This article discusses young gay
      Norwegian men's interpretations of condom use and nonuse. Meanings mediated by
      (non)use of condoms are meanings in the making rather than antecedently and
      inalterably fixed. How young gay men interpret (non)use of condoms varies with
      and depends upon context or relationship. In this article, young men's readings
      of (non)use of condoms are discussed in the contexts of (anal) sex; surrender to
      pleasure; semen and intimacy; and respect, disrespect, and humiliation. How
      condom use functions as a sign for both trust and mistrust also is discussed.

PMID- 11288620
TI  - The pollution of incontinence and the dirty work of caregiving in a U.S. nursing
      home.
AB  - In U.S. nursing homes, it is the job of nursing assistants to tend to residents'
      basic bodily needs, including elimination and incontinence care. Given their
      frequent contact with pollutants, aides are very much at risk of becoming
      "polluted people." In this article, I investigate how nursing assistants'
      continual contact with contaminating substances impacts their status within the
      workplace, their relationships with others, and their attitudes toward their work
      and themselves as workers. I also explore how aides manage their encounters with
      pollutants and their stigmatized role as "dirty workers." In doing so, I hope to
      explicate the meaning of elimination and of incontinence caregiving in the United
      States.

PMID- 11288621
TI  - Public beliefs about GM foods: more on the makings of a considered sociology.

PMID- 11288622
TI  - [Placental location and its influence on the position of the fetus in the
      uterus].
AB  - There are different opinions concerning the influence of the placental
      localization on the position of the fetus in the uterus. Two options are
      suggested in breech presentation--placenta praevia and cornual localization as
      possible causes for breech presentation. The aim of the present prospective study
      is to establish the influence of placental localization on the fetal position in
      the uterus. Two groups of pregnant women were examined--the first with cephalic
      resentation (n = 125) and the second with breech presentation (n = 124). All of
      the pregnant women examined were nulliparas, with term pregnancy (37-40 weeks).
      Uterine and fetal abnormalities were excluded. The localization of the placenta
      was determined by ultrasonography. The cornu-fundal localization of the placenta
      was found in 4.8% in the pregnant women with cephalic presentation and 62.6% in
      pregnant women with breach presentation. Placenta praevia or low insertion of the
      placenta was found in 3.2% of the cases with breech presentation and in none of
      the cases with cephalic presentation. The authors conclude on the basis of the
      data in the study that the localization of the placenta influences the fetal
      position in the uterus.

PMID- 11288623
TI  - [Non-obstetrical indications for cesarean section at the Obstetrics-Gynecology
      Department of the Higher Medical Institute, Plovdiv].
AB  - The authors have examined retrospectively the non-obstetrical indications for
      Caesarian section over a six-year period (1994-1999). Such indications have been
      related to extra-genital diseases. For this period there have been 6647 births,
      908 of which (13.66%) by Caesarian section. For non-obstetrical indications 146
      CS have been performed. The greatest number of CS is due to ophthalmological
      reasons--84. The current concepts for performing CS in cases of eye pathology and
      non-medical indications are discussed.

PMID- 11288624
TI  - [Elective cesarean section during delivery and emergency. Interrelations among
      different indicators].
AB  - The authors made a retrospective research over 466 Cesarean sections for a 4 year
      period. The cases were divided into three groups: 1. Elective Cesarean section 2.
      Cesarean section during the delivery 3. Emergency Cesarean section The purpose is
      to compare clinical results for the mother and baby in the three groups. We found
      that: 1. The best results we found in the first group 2. Similar results may be
      achieved in the other groups, if continuous monitoring of the labor, and if there
      are possibilities for an emergency operative treatment.

PMID- 11288625
TI  - [Causes for healing complications in episiotomy].
AB  - The aim of the study is to look for the most probable causes of disturbed healing
      of episiotomy. The study is prospective and includes 33 early puerperal women
      without data of infection disease or risk factor like: PPROM, vulvovaginitis,
      chorioamnionitis, diabetes, obesity and others. The cases are divided in two
      groups: the first group are 12 women with normal healing of episiotomy; the
      second group 21 cases with wound healing complications, divided in three
      subgroups: 13 with edematous and erythematous edges; 5 with superficial
      dehiscence in me aria of introitus vaginae; 3 with entirely open episiotomies.
      RESULTS: For a period of 5 years the mean rate of entirely open episiotomy is
      1.07%. According our data the process of episiotomy healing is not influence by:
      age of me women, parity, duration of labor, the weight of the neonate. For the
      episiotomy outcome is important the experience of the obstetrician. The shorter
      time between ROM during labor and delivery and use of cat-gut stitches on the
      skin of the perineum show tendency of poor healing of the episiotomy.

PMID- 11288626
TI  - [Dynamics and structure of neonatal mortality in Bulgaria - Part II. Dynamics and
      structure of neonatal deaths in the university maternity hospital "Maichin Dom"].
AB  - AIM OF THE STUDY: To analyse the state and the structure of the neonatal
      lethality in the largest perinatal center of Bulgaria 'Maichin dom' during the
      last five years, and to compare them with the national data on neonatal
      mortality. MATERIAL AND METHODS: A retrospective study on the evolution of
      neonatal lethality in the recent 5 years and on its structure during the last 2
      years was fulfilled using the data of the Department of Neonatology of the
      University hospital 'Maichin dom' concerning the infants' lethality. The results
      were compared to the national data on infants' mortality (in 28 days of life) and
      presented graphically. RESULTS: The level of neonatal lethality in the University
      hospital increased invariably until 1997, when it reached the highest peak
      (12.7@1000), after that it decreased to 10.3@1000 in 1998. This tendency is
      predominantly due to the early neonatal mortality, which raised from 6.7@1000 in
      1994 to 8.5@1000 in 1998, and remained at the same level in the last two years.
      The leading causes of neonatal lethality in the perinatal center are the
      congenital malformations--40.6@1000, which is higher than in the country. The
      congenital anomalies of central nervous system account to 75@1000 of all lethal
      malformations. The perinatal asphyxia is the second cause of death--34.7@1000,
      which is considerably less than in the country--41.3@1000. The neonatal
      respiratory distress syndrome is the third main cause of death in the neonatal
      period--9.4@1000 in the hospital; 10.9@1000--in the country. The neonatal
      lethality is mainly due to the premature infants--82.5@1000 in 1997 and 90.6@1000
      in 1998. The relative portion of the term infants considerably decreased in these
      two years--from 17.5@1000 to 9.4@1000. These numbers are 100 times less than the
      data of the whole country. CONCLUSIONS: The evolution of the neonatal lethality
      in the University hospital 'Maichin dom' has a similar tendency of the neonatal
      mortality in Bulgaria, the increase being mostly due to the early neonatal
      mortality. The leading causes of death are the congenital malformations and
      predominantly the central nervous system defects. The perinatal asphyxia is the
      second most frequent lethal cause with a relative portion which is less than that
      in the country. The lethality of the premature infants in the hospital is 6 times
      less than that in the country and the neonatal lethality of term infants is
      practically discriminated.

PMID- 11288627
TI  - [Endometriosis in adolescence - characteristic features].
AB  - Retrospectively it is established that the beginning of the endometriosis is 3-4
      years after menarche. It can be found between 12-20 years of age in girls with
      congenital abnormality of the uterus and the urinary tract as well as with
      menarche before 11 years of age. Primary predilection areas are ligamentum
      sacrauterine and pelvic peritoneum in cavum Duglassi. Predominant appearance are
      the red lesions, that are cause for complaints--menstrual cyclic pain, nausea,
      vomiting, constipation or diarrhea and abdominal pain. The most used diagnostic
      methods are: from uninvasive methods--Sonographya and Tu marker CA-125 and from
      the invasive methods--laparoscopy.

PMID- 11288628
TI  - [Endometriosis in adolescence - treatment].
AB  - Endometriosis is treatment when has expressed symptomatic. In spite of increased
      possibility the current treatment is provisionally. It is applied Danazol, Ru
      486, GnRh agonists. Nafarelin diminishes the pain syndrome in 70% of the cases.
      The relapses are 53.4% for 5 years. However, the GnRH agonists provoke suppress
      on E2, which lead to transient bones demineralization. Therefore they are
      impracticable in adolescent age when the bone growth occurs. Therefore in
      adolescent age for treatment on the endometriosis is recommend low-dose oral
      contraceptive drugs and in a case of inadequate effect to make Laparoscopic
      vaporization on the endometriomas by trained operator.

PMID- 11288629
TI  - [Administration of low-molecular-weight heparins in obstetrics].

PMID- 11288630
TI  - [Fetal oxygen saturation during normal delivery].
AB  - The aim of the study is to monitor fetal oxygen saturation--SpO2 during
      uncomplicated labour; to assess normal values and compare them to the data from
      fetal blood analysis and from clinical finding in the newborn. The study includes
      53 pregnant women in term during active labour without evidence of fetal
      distress. Study is carried out with Nellcor-N 400--a system for measuring fetal
      pulse oxymetry and fetal pulse rate; oxygen sensor FS-14 and printer P-400
      /Nellcor Bennet Incorporation/. Fetal pulse rate is monitored by cardiotograph
      Hewlett Packard. Mean duration of monitoring during first stage of labour is 98
      +/- 48 min, versus 37 +/- 11 min during second stage. Mean values of SpO2 are
      48.8 +/- 10% during the first stage of labor v/s 46 +/- 9.6% during second stage.
      Baby is born in good health--Apgar score more than 7 and mean pH value from
      umbilical artery 7.25. The conclusion is made that pulse oxymetry is an easy non
      invasive method for fetal monitoring without side effects concerning woman on
      labour and fetus. A relatively large range of variations of normal values is
      observed.

PMID- 11288631
TI  - [Diagnosis and differential diagnosis of space-occupying disorders of the
      umbilical cord].
AB  - In connectiin with a clinical case of a circumscribed edema of the umbilical cord
      the authors considered the space-occupied disorders of the umbilical cord. The
      tumorous and nontumorous lesions of the umbilical cord as well as the criteria
      and their diagnostic difficulties are discussed. The authors pay attention to the
      complications of such disorders in the pregnancy and their possible influence on
      the fetus.

PMID- 11288632
TI  - [Transvaginal ultrasonography as a screening method for ovarian carcinoma].

PMID- 11288633
TI  - [Stimulation of ovulation and ovarian carcinoma. Literature Review].

PMID- 11288634
TI  - [Use of frozen human semen].
AB  - The necessity of establishing of monitored donor's genetic bank in Bulgaria is of
      exceptional necessity at the moment, when health care in our country is in
      reorganization and is set on a new base. Our studies were directed towards the
      organization of bank for cryopreservation of spermatozoa taken of: Donor's
      genetic material for the needs of obstetric and gynaecological laboratories From
      men that are expected to go through an X-ray or chemical treatment because of
      tumors or are planned for operation of the testicules. The genetic bank in IBIR
      is organised accordance with Bulgarian Legislation.

PMID- 11288635
TI  - [Influence of elective abortion, up to the 12th week of pregnancy, on the
      dimensions of the cervix].
AB  - The conflicting data in the literature about the influence of the voluntary
      abortion on the cervix uteri and its effects has lead us to the idea to examine
      by ultrasound the changes in the cervix uteri as a result of elective abortion.
      137 healthy women at the average age of 26.7 years have been examined, out of
      which 31 were pregnant for the first time. 15 with no child-births but with one
      previous voluntary abortion, 30 with no child-births but with more than one
      voluntary abortion, 35 with one child-birth and 26 with more than one child
      birth. Out of the total 76 women, 64 come back for ultrasound examination of the
      parameters of the cervix uteri between the first and the second week after the
      abortion (10 + 3 days). The abortion has been done up to 12 guest. week under
      intravenous anesthesia, I Hegar dilatation of the cervical canal and vacuum
      aspiration. Each ease has been examined with an ultrasound (Kontron--France),
      supplied with a 7.5 MHz vaginal transducer. The results show that the measured
      length and width of the cervix uteri among the groups with differing number of
      elective abortions but with no child-births do not reveal a great statistical
      difference. With the increase of the number of abortions the width of the
      cervical canal shows a tendency to expand minimally. With women pregnant for
      first time and having elective abortion, of all parameters of the cervix only
      OECC remains a little wider than before the abortion. Child-births change
      dramatically the dimensions of the cervix uteri--the cervical canal expands, the
      cervix shortens and at the same time becomes wider. We can safely assume that the
      elective abortion under intravenous anesthesia within 8-9 g.w. with Hegar
      dilatation about 10 mm and vacuum aspiration has not shown traumatic effect on
      the cervix uteri according to its dimensions.

PMID- 11288636
TI  - [Immune infertility after mumps orchitis?].

PMID- 11288637
TI  - [Inborn laryngeal cysts - description of a case with fatal outcome].
AB  - The authors describe a case of a newborn baby with inborn laryngomucocaele,
      living 14 days after birth. The newborn baby was looked after with artifical
      lentilation. Because of the inability of self breathing the baby underwent
      tracheostomia. The autopsy revealed the presence of laryngomucocaele.

PMID- 11288638
TI  - [Parovarian cyst in an 18-year-old patient].
AB  - A rare case of a large paraovarian cyst in an unusually young 18-age-old patient,
      filling up the whole abdominal cavity, is described. It is concluded that an
      accurate and precise diagnostics, and also an experienced surgical team would be
      required in such a surgery as complete surprises can take place effecting its
      course and outcome.

PMID- 11288639
TI  - [Influence of the phytoestrogen drug, SoyaVital, on climacteric symptoms].
AB  - The results of phytoestrogen drug SoyaVital on the climacteric symptoms are
      presented. The preparation consists of 35 mg isoflavones with high content of
      genistein in one capsule. A group of 26 patients having climacteric symptoms have
      been treated by one capsule per day for a period of 12 weeks. The evaluation of
      the symptoms by Kuppermann score decreased statistically significant by 30.06%.
      The authors recommend SoyaVital as an alternative to the hormonal replacement
      therapy.

PMID- 11288640
TI  - [Prophylaxis of postabortion endometriosis with Cedax].
AB  - The authors investigate the possibilities for antibiotic prophylactics of
      postabortion endometritis with the drug Cedax in high risk patients.

PMID- 11288641
TI  - [Clinical trial of Magnerot in the treatment of a threatened abortion after a
      previous delivery].

PMID- 11288643
TI  - Ethics in action. A competent, elderly Chinese woman who needs immediate
      treatment says she can't give consent because she must wait for her family to
      arrive to give approval.

PMID- 11288644
TI  - Don't use outdated approaches for critically ill children.

PMID- 11288642
TI  - [Retrospective analysis (1996-1998) of the treatment results with PgE2 (3 mg) of
      pregnant women with induced birth indications because of unsatisfactory cervix
      condition].
AB  - The aim of the retrospective analysis is to estimate the results of PGE
      treatment/or cervical ripening with Bishop score < or = 4--effectiveness and
      safety. The research includes 60 patients with different induction indications.
      The comparative analysis has been carried out between 2 groups of patients with
      premature ruptiere of the ammotic membranes. The first group includes 22 patients
      treated only with Pg; and the second one includes 18 patients treated only
      with....

PMID- 11288645
TI  - Practical tips for domestic violence screening.

PMID- 11288646
TI  - The right way to do blood cultures.
AB  - Blood samples contaminated by skin-surface bacteria can increase hospital stays,
      cause the needless use of antibiotics, and cost thousands of dollars per
      incident. A few simple steps can reduce contamination and save patients and
      healthcare providers money, time, and heartache.

PMID- 11288647
TI  - Do you really listen to patients?
AB  - Effective communication with patients starts with active listening. Tune in to
      the meanings behind their words, as well as their nonverbal cues, so you can
      understand their mindset and adjust your communication style accordingly.

PMID- 11288649
TI  - How to cope with job stress.

PMID- 11288648
TI  - Dolasetron for chemo nausea.

PMID- 11288650
TI  - One nurse's story. Be careful. You can lose yourself in your job.

PMID- 11288651
TI  - Epidural analgesia. Your role.
AB  - For postoperative pain, epidural analgesia may be the most effective medicine.
      But there are a few things nurses need to know about managing the patient,
      including the early warning signs of complications and what to do--and what not
      to do--if they occur.

PMID- 11288652
TI  - Diabetes update. The untold story of disease progression.
AB  - Diabetes is often found hand-in-hand with ischemic heart disease. We now have a
      greater understanding of why that is and how diabetes itself progresses.
      Understanding those links is crucial to your role in patient education.

PMID- 11288653
TI  - Compressor nebulizer systems.

PMID- 11288654
TI  - Reduce your risk in the managed care jungle.

PMID- 11288655
TI  - What caused this patient's sudden liver dysfunction?

PMID- 11288656
TI  - Telephone triage. A common sense approach.
AB  - Can you accurately assess a patient's condition over the telephone? Can you
      determine which patients should be seen in the ED or the office, and which
      patients can follow your advice for home treatment? Telephone triage can save
      time and money--if it's done effectively.

PMID- 11288657
TI  - Facts about asthma.

PMID- 11288658
TI  - Presidential address. "Medicine as a profession for ladies".

PMID- 11288659
TI  - Pathogens and politics at Porton Down.

PMID- 11288663
TI  - London medicine.

PMID- 11288662
TI  - Aspects of surgery during the Anglo-Boer War.

PMID- 11288661
TI  - Music and medicine in the life of Mozart.

PMID- 11288660
TI  - Mood and cancer.

PMID- 11288664
TI  - Medical times.

PMID- 11288665
TI  - Murder and mystery: medical science and the crime novel.

PMID- 11288666
TI  - Inspector General James Barry: Britain's first known woman M.D.

PMID- 11288667
TI  - The Lettsomian Lecture shedding a little light on the bosom.

PMID- 11288668
TI  - Medical education in east London.

PMID- 11288669
TI  - The annual oration. Should we worry about health or health care in an ageing
      society?

PMID- 11288670
TI  - Localization of mRNAs at synaptic sites on dendrites.

PMID- 11288671
TI  - RNA transport and local protein synthesis in the dendritic compartment.

PMID- 11288672
TI  - Neuronal BC1 RNA: intracellular transport and activity-dependent modulation.

PMID- 11288673
TI  - Nucleocytoplasmic mRNA transport.

PMID- 11288674
TI  - RNA localization in Xenopus oocytes.

PMID- 11288675
TI  - Local protein synthesis in invertebrate axons: from dogma to dilemma.

PMID- 11288676
TI  - Nucleocytoplasmic RNA transport in retroviral replication.
AB  - Retroviral replication is highly dependent on post-transcriptional regulation
      because a single primary transcript directs synthesis of many viral proteins. The
      identification and characterization of two post-transcriptional regulatory
      systems (Rev/RRE and CTE) revealed the efficient use of cellular transport
      pathways by retroviruses to achieve production of infectious progeny virus. The
      Rev/RRE system of HIV-1 consists of the viral Rev protein which binds to its
      target sequence on incompletely spliced RNAs and channels these into the CRM1
      dependent export pathway, which is normally used for export of cellular proteins
      and RNAs (U snRNAs and 5 S rRNA). The CTE, on the other hand, directly recruits
      the cellular mRNA export receptor TAP to the viral RNA. Both systems have in
      common that they recruit a key player of a specific cellular export pathway and
      this recruitment appears to out-compete the respective cellular target molecules.
      The fact that CTE can functionally substitute for Rev/RRE, yielding a replication
      competent virus, indicates that very short sequence elements are sufficient for
      post-transcriptional control. The presence of short dominant export signals could
      relieve the selective pressure on the remainder of the genome to maintain a
      sequence that is easily exported. The resultant increase in permitted sequence
      space may increase the potential for immune escape, thereby providing a selective
      advantage for the virus. Replication of the CTE-dependent HIV-1 variant is
      significantly impaired compared with the wild-type virus. Considering that post
      transcriptional control in the case of HIV is also used to provide a temporal
      switch from the early phase of regulatory protein expression to the late phase of
      virion production, one may suggest that the CRM1 export pathway is advantageous
      for the rapid delivery of large amounts of cargo (i.e. HIV RNA). This would be in
      accordance with its normal function because CRM1 has been shown to direct the
      nuclear export of cellular regulatory proteins which must be accomplished rapidly
      as well. In summary, retroviruses have evolved fascinating ways to deal with
      their cellular environment and to make use of cellular transport pathways,
      allowing nuclear export of intron-containing RNAs which are normally restricted
      to the nucleus. Specific signals on the viral RNAs recruit key factors of
      cellular export, thus bypassing these restrictions and ensuring efficient viral
      replication.

PMID- 11288677
TI  - Long-lasting hippocampal plasticity: cellular model for memory consolidation?

PMID- 11288678
TI  - Neuronal RNA localization and the cytoskeleton.

PMID- 11288679
TI  - Transcription factors in dendrites: dendritic imprinting of the cellular nucleus.

PMID- 11288680
TI  - RNA trafficking in oligodendrocytes.
AB  - A2RE and hnRNP A2 have been identified as important cis/trans determinants for
      MBP RNA trafficking in oligodendrocytes. Since A2RE-like sequences are found in
      several different transported RNAs, and since hnRNP A2 is expressed in most cell
      types, this may represent a general RNA trafficking pathway shared by a variety
      of different RNAs in different cell types. In oligodendrocytes, A2RE/hnRNP A2
      determinants are involved in at least four steps in the RNA trafficking pathway:
      (1) export from the nucleus to the cytoplasm, (2) granule assembly in the
      perikaryon, (3) transport along microtubules in the processes, and (4)
      translation activation in the myelin compartment. The components of the cellular
      machinery mediating each of these steps are known. How A2RE/hnRNP A2 determinants
      interact with these components to mediate RNA trafficking is being investigated
      by a combination of: biochemistry to analyze molecular interactions in vitro,
      imaging to visualize molecular interactions in living cells, and computational
      modeling to simulate molecular interactions in the Virtual Cell.

PMID- 11288681
TI  - Extrasomatic targeting of MAP2, vasopressin and oxytocin mRNAs in mammalian
      neurons.

PMID- 11288682
TI  - Endodontic retreatment. Aspects of decision making and clinical outcome.
AB  - Epidemiological surveys have reported that 25%-35% of root filled teeth are
      associated with periapical radiolucencies. Descriptive studies have demonstrated
      that clinicians' decision making regarding such teeth are subject to substantial
      variation. A coherent model to explain the observed variation has not been
      produced. In the present thesis a "Praxis Concept theory" was proposed. The
      theory suggests that dentists perceive periapical lesions of varying sizes as
      different stages on a continuous health scale. Interindividual variations can
      then be regarded as the result of the choice of different cut-off points on the
      continuum for prescribing retreatment. In the present study experiments among
      novice and expert decision makers gave evidence in favour of the theory. Data
      also suggested that the choice of retreatment criterion is affected by values,
      costs of retreatment and technical quality of original treatment. From a
      prescriptive point of view, the presence of a persistent periapical radiolucency
      has often been used as a criterion of endodontic "failure" and as an indication
      for endodontic retreatment. As an alternative decision strategy, the use of
      decision analysis has been proposed. Logical display of decision alternatives,
      values of probabilities, utility values (U-values) of the different outcomes and
      calculation of optimal decision strategy are features of this theory. The
      implementation of this approach is impeded by the uncertainty of outcome
      probabilities and lack of investigations concerning U-values. U-values of two
      periapical health states in root filled teeth (with and without a periapical
      lesion respectively) were investigated in a group of 82 dental students and among
      16 Swedish endodontists. Two methods were used to elicit U-values: Standard
      gamble and Visual Analogue Scale. Large interindividual variation for both health
      states were recorded. The difference in U-values between the two health states
      was found to be statistically significant regardless of assessment method.
      Compared with Standard gamble Visual Analogue Scale systematically produced lower
      ratings. U-values were found to change considerably in both the short and long
      term. Any significant correlation between endodontists' U-values and retreatment
      prescriptions could not be demonstrated. Surgical and nonsurgical retreatment
      were randomly assigned to 95 "failed" root filled teeth in 92 patients. Cases
      were followed clinically and radiographically for four years postoperatively. At
      the 12-month recall a statistically significant higher healing rate was observed
      for teeth retreated surgically. At the final 48-month recall no systematic
      difference was detected. Patients were found to be more subject to postoperative
      discomfort when teeth were retreated surgically compared with nonsurgically.
      Consequently, surgical retreatment tended to be associated with higher indirect
      costs than a nonsurgically approach. In the final part of the thesis it is argued
      that retreatment decision making in everyday clinical practice normally should be
      based on simple principles. It is suggested that in order to achieve the best
      overall consequence a periapical lesion in a root filled tooth that is not
      expected to heal should be retreated. Arguments to withhold retreatment should be
      based on (i) respect for patient autonomy, (ii) retreatment risks or (iii)
      retreatment costs.

PMID- 11288683
TI  - [Occupational data cards as a source of information for health prevention
      purposes].
AB  - The Polish Labour Code as well as directives of the European Union (EU) commit
      employers to ensure safety and health protection at work, including the use of
      all possible measures to reduce or eliminate risk factors occurring in the work
      environment, and to provide the workers with information about the extent of the
      risk and possibilities of its reduction. The fulfilment of this commitment is an
      element of the whole system for the reduction of accidents at work and rates of
      occupational diseases in the economically active populations. The effectiveness
      of the measures taken by employers depends on a number of agents, and the
      identification of occupation-related risk factors plays among them a key role. It
      is also important to define predisposition to and limitations in performing
      certain jobs which allows to select a suitable occupation, to direct properly the
      process of preparing candidates for particular jobs and to monitor health
      condition during employment. Activities orientated towards so called human factor
      in labour processes should be linked with the creation of healthy working
      conditions by adopting technical solutions aimed at eliminating and reducing
      potential health risks. In this context the establishment of an effective
      information system able to identify risk factors, possible hazards and/or
      arduousness in the work environment is of great importance. A lack of sources of
      comprehensive information about risk factors and hazards related to various
      occupations, health effects and relevant preventive interventions is a problem
      faced not only by Poland but also by many other countries. To this end an
      international team for developing a multi-language set of International Hazard
      Datasheets on Occupations available in the Internet has been set up on the
      initiative of the International Labour Organization (ILO). Due to this initiative
      it will be possible to distribute widely International Hazard Datasheets on
      Occupations and thus help people in their choice of occupation before employment,
      and to up-date data according to technological progress and organisational
      changes. International Hazard Datasheets on Occupations which are now developed
      the main stress is put on defining hazards with possible traumas, as well as
      harmful factors, including psychophysical ones. Sheets should also include
      information about potential, adverse health effects and necessary preventive
      measures. In the professional literature one may find references with broad
      description of problems related to different occupations and relevant legal
      regulations. International Hazard Datasheets on Occupations are developed in
      individual countries, then translated and verified in view of specific
      technological processes applied. They will be used by the Labour Inspection, work
      safety and hygiene inspectors, sanitary and epidemiological stations, those
      responsible for qualification of candidates who apply for admission to vocational
      schools, occupational medicine physicians and general practitioners. They will
      also be used to produce various instructions, guidebooks and recommendations on
      safety at work and preventive measures.

PMID- 11288684
TI  - [Personnel exposure during interventional radiologic procedures].
AB  - Intervention radiology, known also as intravascular surgery, is a new medical
      specialisation that develops very rapidly. Radiological procedures performed
      under fluoroscopy include: dilatation of stenosed vessels, recanalization or
      vascular embolization and angioanastomosis. Although these procedures have been
      initiated by radiologists, the majority of them are performed now by physicians
      who are specialised in medical disciplines other than radiology (cardiologists,
      vascular surgeons, gastroenterologists, etc.). All these specialists are always
      aware of the fact that during radiological procedures, both the personnel and the
      patients are at risk of ionizing radiation. For that reason monitoring of the
      exposure in this occupational group is of particular importance. Bearing in mind
      that members of surgical teams are often in direct contact with x-ray tube, it is
      assumed that routine individual dosimetry of staff occupationally exposed to x
      rays do not provide adequate assessment of the exposure risk. This paper
      describes measurements carried out among operating surgeons who perform the
      following procedures: cardiological interventions (percutaneous transluminal
      coronary angioplasty (PTCA) and bypass with preceding coronarography);
      neuroradiology (aneurysm embolization); and intravascular surgery within
      abdominal cavity (TIPS, nephrostomy). Dosimetric assessment was carried out in
      operating surgeons who are exposed mostly among the members of surgical teams as
      they have to be in direct contact with radiation sources. A comprehensive
      assessment of exposure included the following measurements: equivalent dose for
      the hands (measured by a specially designed finger dosimeter); equivalent dose
      for the trunk protected by a lead apron (a dosimeter placed under apron); and
      equivalent dose for the neck (a dosimeter placed on the upper, external edge of
      apron). In addition, a dose product and the surface of primary beam were measured
      (Diamentor dosimeter, PTW, Frieburg) which allowed to define the correlation
      between the entrance air kerma, measured with thermoluminscence dosimeters, and
      the amount of primary radiation emitted during the monitored procedure. In all,
      the surgical teams were monitored during 42 intervention procedures. The results
      of the study revealed that an operating surgeon is most exposed. The values of an
      annual effective dose and an annual equivalent dose for the hands and eyes,
      estimated for individual procedures, were as follows: (a) cardiological
      angioplastic procedures: effective dose--25 mSv, equivalent dose for the hands-
      438 mSv, equivalent dose for the eyes--265 mSv; (b) intravascular angioplastic
      procedures within the abdominal cavity and neuroradiological procedures:
      effective dose--4 mSv, equivalent dose for the hands--360 mSv, equivalent dose
      for the eyes--41 mSv. It should be stressed that the aforesaid maximum doses do
      not exceed relevant standard annual limits binding in Poland.

PMID- 11288685
TI  - [Evaluation of voice quality in students from teaching colleges].
AB  - Vocal disorders are very common occupation-related disease in teachers. Their
      remarkable incidence might be associated with inappropriate techniques of speech
      and poor vocal hygiene. The aim of this study was to assess the function of vocal
      organ including voice emission technique in persons starting their teaching
      occupation. The study group included 66 female students at Teaching College.
      Their were thoroughly interviewed and subjected to laryngological, phoniatric and
      videostroboscopic examinations. All subjects reported subjective symptoms after
      vocal effort. Hoarseness and throat dryness were the most common. In the majority
      of students functional vocal disorders were observed. In 30% of them
      insufficiency of glottis and in four (6.1%) students soft vocal nodules were
      found. Signs and symptoms of vocal diseases were more frequent in a subgroup of
      students exposed to increased vocal effort during their professional education.
      The results indicate that young teachers are not sufficiently prepared for
      increased vocal strain, apparently associated with their profession. It is indeed
      necessary to introduce preventive programs including special training of
      appropriate speech technique, into the curricula of schools for teachers.

PMID- 11288686
TI  - [Limits in the use of cobalt filters for protection against infrared radiation].
AB  - Cobaltic filters are widely used to protect eyes against infrared radiation. They
      absorb a greater part of the incident on the filter radiation. The radiation
      absorbed by the filter enhances its temperature and thus increases infrared
      radiation regenerated by the filter. This paper describes the study of the effect
      of Tk cobaltic filter exposed to infrared radiation in the range from 500 W/m2 to
      3000 W/m2 on the quantity of infrared radiation regenerated by the filter. The
      results of the study show the increase in the filter temperature depending on the
      filter irradiance and the exposure duration. In the case of the filter exposure
      to irradiance of 3000 W/m2 lasting longer than 10 min the filter temperature may
      go over 120 degrees C. Radiation regenerated by such a filter reaches about 1250
      which exceeds the safe value for ocular exposure. On the basis of the results
      obtained the conditions for protecting eyes against infrared radiation by
      cobaltic filters are described.

PMID- 11288687
TI  - [The usefulness of the Health Status Questionnaire: D. Goldberg's GHQ-12 and GHQ
      28 for diagnosis of mental disorders in workers].
AB  - The General Health Questionnaires, developed by D. Goldberg (GHQ-12 and GHQ-28),
      are self-administered screening instruments designed to detect current
      diagnosable changes in the mental health status and to identify cases of
      potential mental disorders leaving a detailed diagnosis to a psychiatric
      interview. The General Health Questionnaires were designed for the use in primary
      health care settings, in the general population surveys or in general medical
      practice. The validation studies of the Polish version of GHQ-12 and GHQ-28 are
      described. The internal consistency coefficients (Cronbach alpha) reached the
      value of 0.859 for GHQ-12 in the study of 2540 employees, and 0.934 for GHQ-28 in
      the group of 1108 employees. The coefficients obtained in our studies are
      comparable to those reported by other authors who carried out investigations in
      populations of various countries. Test-retest reliability (ru approximately 0.7)
      seems to be good enough, taking account of the fact that the methods presented
      are aimed at diagnosing the state of mental health and not its stable traits.
      Having obtained significant differences in scores assigned to patients examined
      in settings at different levels of health care (a significant increase in GHQ
      scores of patients examined in psychiatric clinic as compared to patients of
      primary health care settings) it may be concluded that the criteria validity of
      both questionnaires is satisfactory.

PMID- 11288688
TI  - [Evaluation of allergic sensitivity to the virkon disinfectant preparation widely
      used in Poland].
AB  - The aim of the study was to define the sensitising effect of Virkon, a
      disinfectant widely used in Poland, especially in hospitals. The study was
      carried out on guinea pigs, using the maximisation test according to Magnusson
      and Kligman, modified by Krysiak. The assessment of dermal changes presented in
      the percentage of sensitised animals, being thus far the criterion adopted by
      Magnusson and Kligman, has been expanded to include our own criteria covering the
      intensity of reactions of testing samples and the results of eosinophilic and
      basophilic tests in peripheral blood. Using these parameters and applying
      pathomorphological examinations it was possible to indicate the difference in the
      intensity of sensitising effect of Virkon, depending on the concentration used.
      The results of the study showed that 1% aqueous solution of Virkon is the optimum
      concentration for monitoring its sensitising effects in people having contact
      with this substance.

PMID- 11288689
TI  - [Risk factors for preterm birth in a group of unemployed women. II. Analysis of
      independent variables].
AB  - The incidence of preterm birth is conditioned by a number of factors. The
      identification of these factors in individual groups of women helps to adopt well
      oriented preventive measures. The analysis of logistic regression allows to
      identify significant and independent factors responsible for preterm birth. This
      paper describes the results of the analysis carried out in the group of non
      employed women. The results revealed two following independent factors of risk
      for preterm birth in the study group of women: the state of health and the burden
      of considerable physical strain resulting from difficult economic situation of
      women.

PMID- 11288690
TI  - [Characteristics of jobs and workers employed in municipal waste collection and
      disposal by the city of Lodz].
AB  - Characteristics of jobs and workers engaged in the collection and disposal of
      waste was based on a specially developed questionnaire. Five occupational groups
      were selected: domestic waste collectors, waste relading workers, waste
      composting workers, waste sorting workers, workers at landfill sites. In
      addition, five job posts were selected: heavy equipment operators, waste sites
      workers, waste loaders, waste sorters and waste truck drivers. The analysis of
      characteristics revealed that among job-related burdens reported by the workers
      the following were found most noxious: repugnant odour, high dust concentrations,
      required physical effort and changing atmospheric conditions. Nevertheless, the
      workers in question did not claim any occupation-related illnesses or symptoms.
      The majority of respondents assessed their health as good or very good.

PMID- 11288692
TI  - [Occupational exposure to electromagnetic fields and its health effects in
      electric energy workers].
AB  - Power frequency (50 to 60 Hz) electromagnetic fields (EMF) are briefly
      characterised, EMF sources occurring in the electromagnetic industry are
      discussed, and methods for and problems involved in the evaluation of individual
      occupational EMF exposure are also presented. The results of certain cohort
      industrial and case-referent studies indicate slightly enhanced risk of brain
      cancer and leukaemia in the group under study. The meta-analysis of the results
      obtained from numerous studies, published recently, showed a relative risk (RR)
      of 1.1-1.3 for leukaemia, and of 1.1-1.2 for brain cancer. Only a few studies
      demonstrate a dose-effect relationship for malignant neoplasms which decreases
      the power of the hypothesis on the cause-effect relationship. Among health
      effects of EMF exposure in electric utility workers, other than malignant
      neoplasms, an increased risk of certain diseases of the circulatory and
      neurological systems has been reported. The difficulty in the assessment of
      individual exposure is the main problem in evaluating the relationship between
      EMF exposure and adverse health effects in electric utility workers. We hope to
      investigate this further.

PMID- 11288691
TI  - [Quantitative evaluation for risk assessment of neoplasms caused by exposure to
      chemical substances].
AB  - This work is based on the assumption that work safety and hygiene inspectors or a
      work hygiene inspectors in sanitary and epidemiological station will not develop
      their own dose-response models on the basis of background data. They should be
      equipment with a tool allowing them to assess a given risk in the most simple
      way. Dose-response models for assessing cancer risk induced by carcinogenic
      chemicals are presented in the "Guidelines on health risk assessment of
      carcinogenic agents" published since 1995 by The Nofer Institute of Occupational
      Medicine in Lodz. Nevertheless, it seemed advisable to gather in one publication
      all models published thus far, and by adding relevant comments and necessary
      formulas for calculations, produce a simple set of practical rules of risk
      assessment. All models already published in Guidelines may be divided into two
      groups: linear and non-linear models. In addition, among linear models one may
      differentiate those for asbestos dust exposure because of different nature of the
      relationship between the extent of exposure and likelihood of cancer occurrence.
      The models are given in three tables under the following headings: linear models
      for 21 chemicals, non-linear models for 12 chemicals and linear models for
      asbestos. There are also included formulas that allow to convert dose into
      concentration and concentration into dose, and occupational exposure into
      equivalent exposure over the course of a lifetime, as well as conversion
      coefficients enabling the use of animal experiment results in the assessment of
      human risk.

PMID- 11288693
TI  - [Assurance and assessment of education quality in occupational medicine of
      selected countries of Western Europe and the United States. II. USA].
AB  - The author discusses the studies undertaken with the general aim to provide
      education in occupational medicine and assure its quality assessment in some
      countries of Western Europe advanced more than Poland in this area. It becomes
      quite evident that despite a widespread interest in quality of education, there
      is a lack of basic systemic solutions, and a gap between basic theoretical and
      methodological guidelines and a large number of dispersed reports on concrete
      analytical and evaluation studies can be still observed. In addition to the
      presentation of an inside view of research activities carried out in some
      countries of Western Europe and the United States, based on selected professional
      publications, the author formulates general conclusions on how the assurance and
      quality assessment of education in occupational medicine function in those
      countries.

PMID- 11288694
TI  - [Internal control of working conditions as a form of occupational health and
      safety management--experience of Western European countries and the situation in
      Poland].
AB  - Good occupational health and safety management not only protects workers from
      hazards and health impairment, but also contributes to the success of the
      enterprise as a whole. The internal control of working conditions in an
      enterprise, carried out by an employer, is one of the forms of occupational
      health and safety management implemented widely in many western countries, for
      example in Scandinavian countries and Ireland. This method may serve employers as
      an useful tool for stimulating and developing programmes aimed at improving
      working conditions and supporting workers' health protection against various
      hazards occurring in the work environment. The experience of the western
      countries in developing and implementing the internal control system, and the
      adaptation of the principles of this system to suit Polish conditions helped the
      authors to produce a set of general rules and guidelines addressed to employers
      who decide to use the method of internal control in their enterprises.

PMID- 11288695
TI  - [Outline of the accreditation system for primary units of occupational medicine
      services].
AB  - The development and implementation of the system for the quality assurance of
      services provided by primary units of Occupational Medicine Service (OMS) is
      aimed at establishing occupational health care of workers in terms of high
      quality services. Accreditation is commonly regarded as a useful tool in the
      quality assurance system. The concept of primary OMS unit accreditation is
      discussed, and the suggestions for some new, additional parameters to be possibly
      used in the quality assurance process are presented. It is worth stressing that
      the system proposed is built on the system of control and professional
      supervision adopted by OMS. Although it is planned to establish the Centre of OMS
      Accreditation outside OMS, the observations collected in the course of internal
      controls may be used effectively in the accreditation process. Once an OHS unit
      is granted accreditation, both the employer and employees may be sure that it not
      only satisfies the requirements imposed by law, but also provides services of
      high quality. Such a unit will be recommended by the Centre of OMS Accreditation.
      Other units may also operate on the market but without the Centre's
      recommendation.

PMID- 11288696
TI  - [De Morbis Artificium Diatriba by Bernardino Ramazzini (The tercentenary of the
      first addition)].
AB  - Three hundred years ago, the first edition of "De Morbis Artificium Diatriba", or
      considerations for occupational diseases in workers employed in manufactures and
      the arts--a fundamental work of Bernardino Ramazzini (1633-1714) was published.
      In the work based on very thorough investigations carried out in groups of
      workers representing fifty two occupations, Ramazzini showed an overall picture
      of relationships between working conditions, health and disease. Each section of
      this work starts with a brief description of disability or health impairment
      induced by particular kind of job. This is followed by technical characteristics
      of working conditions, clinical aspects of a given occupational pathology,
      literature review and indications or regulations for combating existing diseases
      or preventing new ones. Interestingly, the size of first edition of the book
      published in 1700 was very small (18 cm in height) as it was intended to be a
      pocket book for practising doctors.

PMID- 11288697
TI  - Apoptosis and karyogamy in syncytia induced by the HIV-1-envelope glycoprotein
      complex.

PMID- 11288698
TI  - [The preventive measures at the time of outbreak in hospital].

PMID- 11288699
TI  - [Rapid diagnosis for infectious diseases: the respective roles of physician and
      medical technologist].
AB  - The outcome of infectious disease greatly depends on the rapidity of making a
      definite diagnosis. For this, smooth and tight cooperation between physician and
      laboratory where medical technologists are working will become to the key. Rapid
      diagnosis for infectious diseases can contribute on the patient care, however the
      laboratory has a self-limitation. That is a seesaw phenomenon; rapidity vs
      accuracy, rapidity vs sensitivity, rapidity vs easygoing, rapidity vs
      carefulness, etc. From the laboratory aspect, medical technologists should
      function as the effective access-point in the evidence-based medicine (EBM), and
      should have a reasonable balance in judging seesaw phenomena, and should be
      keeping up their knowledge and technical skill.

PMID- 11288701
TI  - [Problems in severe infection--a viewpoint of a physician].

PMID- 11288702
TI  - [Rapid diagnosis of infection in emergencies--a viewpoint of medical
      technologists].

PMID- 11288703
TI  - [The present state and problems of the rapid method in microbiology].

PMID- 11288704
TI  - [Response of the hospital laboratory to emergency care].

PMID- 11288705
TI  - [The importance of rapid method in microbiology for clinical organ
      transplantation].

PMID- 11288706
TI  - Genetic modification of cotton seed oil using inverted-repeat gene-silencing
      techniques.
AB  - Inverted-repeat-based gene constructs targeted against two key cotton seed
      specific fatty acid desaturase genes, ghSAD-1, encoding stearoylacvl carrier
      protein delta9-desaturase and ghFAD2-1, encoding microsomal omega-6 desaturase,
      were transformed into cotton. The expression of ghSAD-1 and ghFAD2-1 in the
      inverted-repeat orientation resulted in increased levels of stearic and oleic
      acids, respectively. Interestingly, the content of palmitic acid in both high
      stearic and high-oleic lines was substantially reduced. These materials offer the
      promise of developing cotton seed oil products with greatly improved nutritional
      appeal to consumers.

PMID- 11288707
TI  - Re: Savelberg et al., Gait and posture (1998) 7(1): 26-34.

PMID- 11288708
TI  - Segmental uniparental isodisomy (UPD) for 2p16 without clinical symptoms:
      implications for UPD and other genetic studies of chromosome 2.

PMID- 11288709
TI  - Mutations in SURF1 are not specifically associated with Leigh syndrome.

PMID- 11288710
TI  - A novel mutation and novel features in Nijmegen breakage syndrome.

PMID- 11288711
TI  - Molecular cytogenetic characterisation of a complex 46,XY,t(7;8;11;13) chromosome
      rearrangement in a patient with Moebius syndrome.

PMID- 11288712
TI  - Use of a set of highly     polymorphic minisatellite     probes for the
      identification     of cryptic 1p36.3 deletions in     a large collection of
      patients     with idiopathic mental     retardation.

PMID- 11288713
TI  - A transmitted deletion of     2q13 to 2q14.1 causes no     phenotypic
      abnormalities.

PMID- 11288714
TI  - Keratosis pilaris/ulerythema     ophryogenes and 18p     deletion: is it possible
      that     the LAMA1 gene is     involved?

PMID- 11288715
TI  - Molecular characterisation     of a proximal chromosome     18q deletion.

PMID- 11288716
TI  - Submicroscopic deletions of     the APC gene: a frequent     cause of familial   
      adenomatous polyposis that     may be overlooked by     conventional mutation   
      scanning.

PMID- 11288717
TI  - Homozygosity for a splice site mutation of the COL1A2 gene yields a non
      functional pro(alpha)2(I) chain and an EDS/OI clinical phenotype.

PMID- 11288718
TI  - Mutation and haplotype     analysis of the CFTR gene in     atypically mild
      cystic fibrosis     patients from Northern     Ireland.

PMID- 11288719
TI  - Risk perception and cancer     worry: an exploratory study     of the impact of
      genetic risk     counselling in women with a     family history of breast    
      cancer.

PMID- 11288720
TI  - [5% of patients are responsible for 20% of health care costs in ambulatory
      internist practices. Documentation of diagnoses reveals the morbidity impact of
      high-risk patients on clinical practice of internists (as of 10.10.2000)].

PMID- 11288721
TI  - News fron the National Institute of Nursing Research.

PMID- 11288722
TI  - The Nursing Leadership Consortium on End-of-Life Care: the response of the
      nursing profession to the need for improvement in palliative care.

PMID- 11288723
TI  - Clinical target volume of high-grade glioma.

PMID- 11288724
TI  - Genes encoding staphylococcal enterotoxins G and I are linked and separated by
      DNA related to other staphylococcal enterotoxins.
AB  - Fifteen randomly selected Staphylococcus aureus isolates, known to carry the
      staphylococcal enterotoxin (SE) G determinant (seg), were shown to carry the SEI
      determinant (sei). To determine whether these two genes are linked, two S. aureus
      strains (FRI445 and FRI572), each containing the seg and sei determinants, were
      further analyzed. In these strains, sei is located 2,002 bp upstream of seg.
      Within the intergenic nucleotide sequence are three regions of nucleotide
      sequence with significant identity to the sequences of other SE genes.
      Characterization of the DNA regions surrounding the seg and sei determinants will
      allow a better understanding of the association between these two genes and may
      explain why they are so frequently observed simultaneously in S. aureus isolates.

PMID- 11288726
TI  - Production of polyclonal antibodies in mice against cobratoxin, botulinum toxin
      and ricin without altering their toxicity or use of adjuvant.
AB  - Purified venom components, botulinum toxin and ricin have been successfully used
      as immunogenes, after converting to toxoids and using adjuvant for production of
      polyclonal antibodies in animals. This communication reports that polyclonal
      antibodies specific to cobratoxin, botulinum toxin and ricin were generated in
      Balb/C mice. The toxins were used for immunization without adjuvant and without
      altering their toxicity or converting them to toxoids. Initially, lethal dose for
      botulinum toxin, cobratoxin and ricin were determined in mice and found to be 1
      microg, 4 microg and 2 microg, respectively. For the production of antibodies
      mice were injected with half lethal dose of the toxins in natural form four
      times, two weeks apart. The potency of antitoxins was assayed by enzyme-linked
      immunosorbent assay. High titer antibodies were generated by botulinum toxin,
      cobratoxin and ricin after three injections consisting of half mouse lethal dose.
      Such minute amounts of botulinum toxin, cobratoxin and ricin in their natural
      form were able to produce high titer antibodies, perhaps because these toxins may
      fall in the category of super-antigens.

PMID- 11288725
TI  - Expression, purification and biochemical characterization of a recombinant
      phospholipase A2, with anticoagulant activity from Agkistrodon halys Pallas.
AB  - A cloned cDNA encoding a PLA2 from Agkistrodon halys Pallas was found to have
      conservative residues Glu53 and Trp70 but with Lys56 and Lys67 substituted by
      Thr56 and Asp67, respectively, when compared with sequences of other class II
      PLA2 with anticoagulant activity. It was inserted into a temperature-sensitive
      bacterial expression vector and effectively expressed in Escherichia coli RR1.
      The protein was produced as insoluble inclusion bodies and recovered by
      centrifugation after enzyme digestion. By washing to partial purification, the
      expression product was refolded and was purified by FPLC superose 12 to appear as
      a single band in SDS-PAGE. The recombinant protein proved to have obvious
      enzymatic, anticoagulant and hemolytic activities, which were removed after
      modification by p-BPB. These findings suggest that the pharmacological activities
      of this recombinant PLA2 may be related to its catalytic activity and warrant
      further research on the structure-function relationships of the pharmacological
      site of the PLA2 from Agkistrodon halys Pallas.

PMID- 11288728
TI  - Identification of key residues responsible for enzymatic and platelet-aggregation
      inhibiting activities of acidic phospholipase A2S from Agkistrodon halys Pallas.
AB  - Site-directed mutagenesis was used to probe the structural and functional
      relationship of acidic phospholipase A2 from Agkistrodon halys Pallas. The
      mutants are AP-E6R (E6R), AP-D115K (D115K), AP-6R115K (E6R, D115K), AP-Y118M
      (Y118M), and AP-W119T (W119T). All mutants were inserted into a bacterial
      expression vector and effectively expressed in E. coli RR1. The purified
      recombinant enzymes were used to assay for enzymatic and inhibiting platelet
      aggregation activities. The enzymatic activities of AP-D115K, AP-Y118M and AP
      W119T are close to that of denatured-refolded acidic phospholipase A2, while the
      enzymatic activities of AP-E6R, AP-6R1 15K are lower than that of denatured
      refolded acidic phospholipase A2 (AP-WT). In these five mutants, AP-Y118M showed
      strongest inhibiting effect on platelet aggregation, which is the same as that of
      AP-WT, AP-W119T showed only modest activity and AP-E6R, AP-D115K, AP-6R115K
      showed little activity. To study the structural and functional relationships
      among these five mutants, molecular modeling of these five mutants was done. The
      roles of various amino acid residues in the enzymatic activity and
      pharmacological activity of acidic phospholipase A2 are discussed.

PMID- 11288727
TI  - Amino acid sequence of a neurotoxic phospholipase A2 enzyme from common death
      adder (Acanthophis antracticus) venom.
AB  - The amino acid sequence of the first neurotoxic phospholipase A2, acanthoxin A1,
      purified from the venom of the Common death adder (Acanthophis antarcticus) was
      determined. Acanthoxin A1 shows high homology with other Australian elapid PLA2
      neurotoxins, in particular Acanthin-I and -II, also from Death adder, Pseudexin A
      from the Red-bellied black snake (Pseudechis porphyriacus), and Pa-12a and Pa-9c
      from the King brown snake (Pseudechis australis). Acanthoxin A1 is a single-chain
      118 amino acid residue PLA2, including 14 half cystine residues and the essential
      residues forming the ubiquitous calcium binding pocket and catalytic site.
      Critical analysis of the residues hypothesized to be important for neurotoxicity
      is presented.

PMID- 11288729
TI  - The biological assessment of flora and fauna as standards for changes in the near
      shore ocean environment: a study of Barbers Point Harbor.
AB  - The biological assessments of the flora and fauna in the near-shore ocean
      environment, specifically Barbers Point Harbor (BPH), demonstrate the usefulness
      of these biological analyses for evaluation of the changes occurring following
      man-made excavation for expansion of the harbor. The study included
      identification and enumeration of macroalgae and dinoflagellates and analyses of
      herbivores and carnivores in four areas within the perimeter of the harbor and
      the north and south entrances into the harbor. Numbers of macroalgae varied
      between 1994 and 1999 surveys, with significant decrease in numbers in stations
      C, D and E. Stations A and B were similar between 1994 and 1999 with a slight
      increase in 1999. The significant differences were shown with the appearance of
      Gambierdiscus toxicus (G toxicus) in 1999 among the algae in stations A and B.
      Assessment of herbivores and carnivores with the immunological membrane
      immunobead assay using monoclonal antibody to ciguatoxin and related polyethers
      demonstrated an increase in fish toxicity among the herbivore from 1994-1999 (22%
      increase) with a decrease (22%) in non-toxic fish. This was also demonstrated in
      the carnivores, but to a lesser degree. It is suggested that the biological
      analyses of the flora and the fauna of the near-shore ocean environment are
      appropriate to assess the changes that occur from natural and man-made
      alterations.

PMID- 11288730
TI  - Chelonodon patoca, a highly toxic marine puffer in Japan.
AB  - Toxicity of a Japanese marine puffer Chelonodon patoca ("okinawafugu") was
      examined by mouse assay from 1996 to 1999. Frequency of the toxic specimens was
      found to be 100% with high toxicity scores. Among the tissues tested, toxicity in
      the skin ranged from 60 to 6,700 MU/g, in the ovary from 25 to 670 MU/g, in the
      testis from 45 to 550 MU/g, in the muscle from 2 to 390 MU/g, and in the liver
      from 5 to 380 MU/g. The liver, which is known as one of the most toxic organs in
      Japanese marine puffer in general, showed lower toxicity in the present study.
      Thus, the anatomical distribution of toxicity was unique in C. patoca, in
      comparison with that of other Japanese puffers. C. patoca toxin was characterized
      as tetrodotoxin (TTX), 4-epiTTX and anhydroTTX by HPLC.

PMID- 11288731
TI  - Two forms of nerve growth factor from cobra venom prevent the death of PC12 cells
      in serum-free medium.
AB  - Nerve growth factor (NGF) from the venom of cobra Naja kaouthia is highly
      homologous to mouse NGF. However, the differences between these two factors
      include the sequence regions determining the specificity of NGF interaction with
      Trk A or p75 receptors. To test if these variations can bring about dissimilarity
      in biological activity between these two NGFs, we have studied the effect of
      cobra factor on the survival of the primed PC12 cells after serum withdrawal. It
      was found that in a serum-free medium, cobra NGF prevented the death of PC12
      cells with efficacy comparable to that of NGF from mouse submaxillary glands. In
      the course of purification two forms of cobra NGF were observed, both acting as a
      survival and a differentiation factor for PC12 cells in a serum-free medium. The
      form, eluting later from a reversed-phase column, displays survival effect at
      lower concentrations than the earlier eluting one.

PMID- 11288732
TI  - Prostate cancer. What you can do to lower your risk.

PMID- 11288733
TI  - The changing scope of colorectal cancer.

PMID- 11288734
TI  - Percutaneous drainage of echinococcal cysts.

PMID- 11288735
TI  - Body mass and gastro-oesophageal reflux symptoms.

PMID- 11288736
TI  - Faecal calprotectin levels and colorectal neoplasia.

PMID- 11288737
TI  - Sporadic HEV hepatitis in Italy.

PMID- 11288738
TI  - Re-epithelialisation of Barrett's oesophagus.

PMID- 11288739
TI  - Adenocarcinoma arising in columnar lined oesophagus following treatment with
      argon plasma coagulation.

PMID- 11288740
TI  - Outcome of lamivudine resistant hepatitis B virus infection in liver transplant
      recipients in Singapore.

PMID- 11288741
TI  - Gastric cancer in patients with benign dyspepsia.

PMID- 11288742
TI  - Sodium cromoglycate in childhood asthma.

PMID- 11288743
TI  - Tuberculin reactivity.

PMID- 11288744
TI  - Cigarette smoke comparative toxicology.

PMID- 11288745
TI  - When can unfractionated heparin really be useful in the treatment of ulcerative
      colitis?

PMID- 11288746
TI  - Heparin therapy for ulcerative colitis.

PMID- 11288747
TI  - Differential HFE allele expression in hemochromatosis heterozygotes.

PMID- 11288748
TI  - Microsatellite instability as a molecular marker for very good survival in
      colorectal cancer patients receiving adjuvant chemotherapy.

PMID- 11288749
TI  - Intestinal motility and bacterial overgrowth in patients with gallstones.

PMID- 11288750
TI  - Hepatitis B infection in heart transplant patients.

PMID- 11288751
TI  - Mechanisms of action of glatiramer acetate in multiple sclerosis.

PMID- 11288752
TI  - Greg Koski, MD, PhD.

PMID- 11288753
TI  - Failed UCSF/Stanford merger posts total loss of $176 million.

PMID- 11288754
TI  - Disease association, origin, and clinical relevance of autoantibodies to the
      glycolytic enzyme enolase.
AB  - Serum autoantibodies to the glycolytic enzyme enolase have been reported in a
      diverse range of inflammatory, degenerative, and psychiatric disorders. Diseases
      in which these antibodies have been reported in high incidence include autoimmune
      polyglandular syndrome type 1 (80%, 35 of 44), primary (69%, 60 of 87), and
      secondary (58%, 14 of 24) membranous nephropathy, cancer-associated retinopathy
      (68.8%, 11 of 16), autoimmune hepatitis type 1 (60%, 12 of 20), mixed
      cryoglobulinemia with renal involvement (63.6%, seven of 11), cystoid macular
      edema (60%, six of 10), and endometriosis (50%, 21 of 41). In autoimmune
      polyglandular syndrome type 1 patients, all had chronic mucocutaneous candidiasis
      with demonstrated antibody reactivity to candida enolase, which is suggestive of
      cross reactivity or epitope mimicry. Formation of autoantibodies to enolase may
      be a normal process, with reported incidence in apparently healthy subjects
      ranging from 0% (zero of 91) to 11.7% (seven of 60). Nonetheless, we suggest that
      excessive production of these autoantibodies, which are generated as a
      consequence of uptake of enolase by antigen-presenting cells and subsequent B
      cell activation, can potentially initiate tissue injury as a result of immune
      complex deposition.

PMID- 11288755
TI  - Silica and its antagonistic effects on transforming growth factor-beta in lung
      fibroblast extracellular matrix production.
AB  - BACKGROUND: Silicosis, a pneumoconiosis marked by interstitial pulmonary
      fibrosis, is caused by inhalation of free crystalline silica particles. When
      silica particles are injected into the lower lung, they are translocated across
      the epithelium into the interstitial space, where macrophage-derived growth
      factors affect lung fibroblast proliferation and collagen deposition. We
      hypothesized that silica may act directly on pulmonary fibroblasts modifying
      extracellular matrix (ECM) synthesis and that the effects of silica may be
      mediated by transforming growth factor-beta (TGFbeta) overproduction. METHODS: To
      test this hypothesis, we studied a human lung fibroblast cell line (WI-1003)
      exposed to silica in vitro. We investigated cell morphology by electron
      microscopic procedure, cell growth, collagen production, and glycosaminoglycans
      (GAG) composition by radiolabeled precursors. Cytokine and growth factor
      synthesis were evaluated by specific enzyme-linked immunoadsorbent assay kits and
      Northern blotting analysis. RESULTS: Pulmonary fibroblasts internalized silica
      particles without detectable cell damage. Silica directly stimulated collagen
      synthesis and decreased the amount of 3H-glucosamine-labeled GAG. Silica-treated
      fibroblasts secreted less TGFbeta than untreated controls, antagonized the
      stimulatory effect of TGFbeta on ECM synthesis, and reversed TGFbeta-induced
      inhibition of cell proliferation. Northern blotting analysis showed increased
      interleukin-1alpha (IL-1alpha) mRNA after silica treatment. IL-1alpha had no
      influence on collagen synthesis but increased the number of WI-1003 fibroblasts.
      CONCLUSIONS: These results support our hypothesis that lung fibroblasts are
      direct silica targets. However, contradicting our hypothesis, silica antagonized
      TGFbeta activities through a TGFbeta downregulation and an IL-1alpha
      upregulation. The complex pattern of TGFbeta and IL-1alpha regulation in
      pulmonary fibroblasts is imbalanced by silica exposure and might play a key role
      in silica-mediated pulmonary fibrosis.

PMID- 11288756
TI  - B-cell kinase lyn deficiency in patients with systemic lupus erythematosus.
AB  - BACKGROUND: To better understand the molecular background of B-cell overactivity
      characterizing systemic lupus erythematosus (SLE), we examined the expression of
      the CD22 co-receptor and of kinase Lyn, which are involved in signaling
      inhibitory pathways, in B cells from patients with SLE. METHODS: Two-color flow
      cytometry was used to study the expression of surface antigens on freshly
      isolated peripheral B cells from patients with SLE, disease-control patients, and
      healthy volunteers. Intracellular kinases Lyn and Syk were analyzed using Western
      immunoblots, and differences at the messenger RNA (mRNA) level were evaluated
      using semiquantitative polymerase chain reaction (PCR). RESULTS: Expression of B
      cell surface CD22 was intact in patients with SLE, but expression of the B-cell
      kinase Lyn was significantly decreased in resting, as well as in anti-sIgM
      stimulated B-cell-enriched cell lysates obtained from 66% of patients with SLE.
      Lyn deficiency was disease-specific and unrelated to disease activity. Expression
      of B-cell kinase Syk was similar in all study groups. Semiquantitative PCR
      revealed that Lyn mRNA was significantly decreased in lupus patients with
      decreased Lyn protein expression, suggesting that Lyn deficiency may be caused at
      least in part by defects at the transcription level. CONCLUSIONS: Decreased
      expression of Lyn in some patients with SLE represents a B-cell defect that may
      enhance our understanding of SLE molecular pathogenesis by providing rational
      therapeutic targets.

PMID- 11288757
TI  - Association of reactive nitrogen species metabolites, myeloperoxidase, and airway
      inflammation in lung transplants.
AB  - BACKGROUND: We have previously reported that patients who had single or double
      lung transplants had higher concentrations than controls of nitrite and nitrate,
      which are metabolites of reactive nitrogen species (RNS), in bronchoalveolar
      lavage fluid (BALF) and serum. METHODS: This study investigates implications of
      RNS metabolites as markers of airway inflammation in a distinct group of lung
      transplant patients (n = 40). All patients underwent spirometry, routine
      surveillance transbronchial lung biopsies, and bronchoalveolar lavage as required
      by clinical protocol. Four normal controls also had bronchoscopy for measurement
      of BALF nitrite (NO2-) and nitrate (NO3-). BALF NO2- and NO3-, myeloperoxidase
      (MPO), protein, and urea were assayed. Total nitrite (NO2- plus enzymatically
      reduced NO3-) and urea were measured in serum. RESULTS: BALF RNS metabolites were
      mainly NO3-. Forced expiratory volume in 1 s (FEV1) obtained near bronchoscopy
      was compared with best postoperative FEV1. Total nitrite in transplant patients'
      BALF and serum were 3.8 +/- 0.2 and 49 +/- 5 microM, respectively. Total nitrite
      in controls' BALF and serum were 2.2 +/- 0.7 and 19 +/- 2 microM, respectively (P
      < 0.05 compared with transplant values). Serum total nitrite correlated (Pearson
      product moment) with percentage of neutrophils in BALF (R = 0.650, P < 0.0001),
      MPO (R = 0.431, P = 0.0055), change in FEV1 from baseline (deltaFEV1) (R = -0348,
      P = 0.0298), and days after transplantation (R = 0.345, P = 0.0294). None of the
      associated variables, airway inflanmmation (quantified as a score, "B"),
      deltaFEV1, serum, or BALF total nitrite, were explained by infection. Univariate
      analysis of airway inflammation in patients showed that it was associated with
      BALF neutrophils, deltaFEV1, and serum total nitrite. CONCLUSIONS: Serum nitrite
      appears to reflect the degree of airway inflammation in this lung-transplant
      study group.

PMID- 11288758
TI  - Unanticipated favorable effects of correcting iron deficiency in chronic
      hemodialysis patients.
AB  - BACKGROUND: Correction of anemia in hemodialysis patients is seldom completely
      attained, and the response of parameters other than hemoglobin concentration to
      anemia correction has not been evaluated in detail. METHODS: Laboratory
      parameters that suggest iron deficiency occurred in 10-15% of 206 recombinant
      human erythropoietin (rhEPO)-treated patients. Oral iron was given for 9 months
      and intravenous iron thereafter on a patient-specific basis when iron deficiency
      was evident. Eighty-seven hemodialysis patients with data for 12 months were
      followed for another 12 months. A computerized information system enabled data
      management and analysis. RESULTS: With oral iron, serum ferritin decreased (P <
      0.001), indicating further iron depletion. With intravenous iron, hemoglobin
      increased, evidence of iron deficiency decreased, and less rhEPO was needed.
      Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight
      (an index of muscle mass) increased, while blood pressure decreased. Data were
      reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin
      subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular
      hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low
      ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin
      increased only in quartile 1, the quartile with the greatest decrease (52%) in
      rhEPO dose. MCV increased in all quartiles (P < 0.001). Serum albumin increased
      in all MCV quartiles and both ferritin subsets, but significant creatinine/kg
      increase and blood pressure decrease occurred only in the low-ferritin subset.
      CONCLUSIONS: Macrocytosis occurred with intravenous iron replacement. The
      universal MCV increase suggests unrecognized, inadequately treated, folic acid
      deficiency unmasked by an adequate iron supply. There was also improved well
      being. Effects were most clearly evident in patients with deficient iron stores.

PMID- 11288759
TI  - New technique for gene transfection using laser irradiation.
AB  - BACKGROUND: We have developed a gene transfection system using laser beams. The
      principle of this procedure is that a small hole is made in a cell membrane by
      pulse laser irradiation, and a gene contained in a medium is transferred into the
      cytoplasm through the hole. This hole disappears immediately with the application
      of laser irradiation of the appropriate power. METHODS: A pulse-wave Nd:YAG laser
      with a wavelength of 355 nm was used to make a hole in a cell membrane. To trap a
      cell, a continuous-wave Nd:YAG laser with a wavelength of 1015 nm was used.
      Plasmids that encode the enhanced green fluorescent protein (EGFP) gene were
      contained in a medium and transferred to HuH-7 and NIH/3T3 cells with pulse laser
      irradiation. We evaluated transfection efficiency on the basis of the number of
      cells that expressed EGFP. Stimulatory protein 2 cells in suspension were fixed
      using a trapping laser and the neomycin-resistance gene was transfected by pulse
      laser irradiation. We examined cell proliferation in the selection medium.
      RESULTS: Cells that expressed EGFP were recognized in the group that was
      irradiated by pulse laser. No cells expressed EGFP without irradiation.
      Transfection efficiency was approximately 10% at a plasmid concentration of 10.0
      microg/mL. At concentrations greater than 20 microg/mL, the transfection rate
      reached a plateau. We also successfully transfected neomycin-resistance genes to
      cells floating in suspension after fixation that was achieved with trapping laser
      irradiation. CONCLUSIONS: This method enables us to transfect targeted cells, ie,
      cells in suspension as well as attached cells, with a simple technique that does
      not involve harmful vectors. The present method is very useful for gene
      transfection in cellular biotechnology.

PMID- 11288760
TI  - Cortisol-secreting adrenal adenomas express 11beta-hydroxysteroid dehydrogenase
      type-2 gene yet possess low 11beta-HSD2 activity.
AB  - BACKGROUND: 11beta-hydroxysteroid dehydrogenase Type-2 (11beta-HSD2) is an
      unidirectional enzyme that catalyzes the conversion of glucocorticoid hormones
      cortisol and corticosterone (B) into their corresponding inactive forms,
      cortisone, and 11-dehydrocorticosterone (DH-B). We have provided evidence that
      11beta-HSD2 is expressed as messenger RNA (mRNA) and protein in human
      adrenocortical cells, where its activity is inhibited in vitro by the main
      glucocorticoid agonists, adrenocorticotropic hormone (ACTH) and angiotensin-II.
      It seemed worthwhile, therefore, to study the gene expression and activity of
      11beta-HSD2 in cortisol-secreting adrenocortical adenomas. METHODS: Three adrenal
      adenomas that produced Cushing syndrome were recruited. Three normal adrenal
      glands were obtained from patients who underwent unilateral nephrectomy with
      ipsilateral adrenalectomy for renal cancer. 11beta-HSD2 gene expression was
      studied by reverse transcriptionpolymerase chain reaction (RT-PCR) in adenoma and
      normal adrenocortical tissue. Cortisol, B, cortisone, and DH-B production by
      adenoma and adrenal slices in vitro was assayed by quantitative high-performance
      liquid chromatography (HPLC), and the activity of 11beta-HSD2 was evaluated by
      measuring the conversion of [3H]-cortisol to [3H]-cortisone. RESULTS: RT-PCR
      allowed the detection of the 11beta-HSD2 mRNA in the three adrenal adenomas and
      normal adrenal cortices examined. Under basal conditions, adenoma slices secreted
      higher amounts of cortisol and B, but markedly lower amounts of cortisone and DH
      B than adrenal slices. ACTH raised cortisol and B production from both specimens,
      and it lowered cortisone and DH-B yield. The level basal conversion of [3H]
      cortisol to [3H]-cortisone was notably less in adenomas than in adrenals, and
      ACTH decreased it in both tissues. CONCLUSIONS: Collectively, our findings
      indicate that cortisol-secreting adrenal adenomas express the 11beta-HSD2 gene,
      but the activity of the enzyme is suppressed in adenomas when compared with the
      normal adrenal cortex. We advance the hypothesis that the elevated local
      concentration of steroid hormones that occur in adenomas down-regulates 11beta
      HSD2 activity, thereby contributing to their abnormal steroidogenic function.

PMID- 11288761
TI  - Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of
      chronic fatigue syndrome patients, without evidence for altered density or
      affinity of glucocorticoid receptors.
AB  - BACKGROUND: In this study we tested the hypothesis that the increased sensitivity
      to glucocorticoids in chronic fatigue syndrome (CFS)-patients can be attributed
      to an altered functioning of their glucocorticoid receptors (GR). METHODS: For
      this purpose, affinity and distribution of the GR were studied in purified,
      peripheral blood mononuclear cells (PBMC) of 10 CFS patients and 14 controls
      along with the responsiveness of these cells to glucocorticoids in vitro.
      RESULTS: Affinity (Kd) and number of GR was not different in PBMC of CFS patients
      when compared with the controls (Kd, 12.9 +/- 8.9 nmol vs 18.8 +/- 16.2 nmol and
      GR number, 4,839 +/- 2,824/ cell vs 4,906 +/- 1,646/cell). Moreover, RT-PCR
      revealed no differences in GR messenger RNA expression. Nevertheless, PBMC from
      CFS patients showed an increased sensitivity to glucocorticoids in vitro. In CFS
      patients 0.01 micromol dexamethasone suppressed PBMC proliferation by 37%,
      whereas the controls were only suppressed by 17% (P < 0.01). Addition of phorbol
      12-myristate 13-acetate to the cultures rendered the cells resistant to
      dexamethasone with regard to proliferation and IL-10 and IFN-gamma production,
      but not to IL-2 and TNF-alpha production in both patients and controls. No
      difference between patients and controls was observed in this respect
      CONCLUSIONS: In conclusion, PBMC of CFS patients display an increased sensitivity
      to glucocorticoids, which cannot be explained by number or affinity of the GR but
      should rather be attributed to molecular processes beyond the actual binding of
      the ligand to the GR.

PMID- 11288762
TI  - How low can you go? Chronic hypoglycemia versus normal glucose homeostasis.
AB  - BACKGROUND: Set point errors in glucose homeostasis that result in chronic, mild
      hyperglycemia in the setting of maturity onset diabetes of the young have been
      described. Similar set point errors may exist that result in chronic,
      asymptomatic glucopenia. CASE: A healthy 39-year-old female was referred for
      evaluation of chronic, persistent, and asymptomatic glucopenia that persisted
      over the prior several years with a record of numerous random plasma glucose
      concentrations between 35 and 45 mg/dL. She denied ethanol intake and family
      history of hypoglycemia or diabetes. She was not taking any medications known to
      cause hypoglycemia, and a urine sulfonylurea screen was negative. Fasting insulin
      and C-peptide levels were not elevated, and pancreatic imaging studies were
      normal. We hypothesized that this patient possessed an error in glucose
      metabolism that resulted in chronic, asymptomatic glucopenia. RESULTS: In a
      series of clinical studies, we demonstrated a nadir plasma glucose concentration
      of 35 mg/dL in the absence of symptoms during a 60-hour fast. C-peptide secretion
      was appropriately suppressed during symptomatic hypoglycemia with exogenous
      insulin infusion, and counterregulatory hormone secretion was intact during
      insulin-induced symptomatic hypoglycemia. Finally, the patient demonstrated an
      incremental increase in insulin concentration in response to minimal increases in
      plasma glucose during a sequential, stepped infusion of 10% dextrose.
      CONCLUSIONS: We conclude that this patient exhibits features of a set point error
      in glucose homeostasis that manifests as chronic, asymptomatic glucopenia.
      Although the mechanism for this condition remains to be elucidated, such set
      point errors do exist and should be considered in the differential diagnosis of
      chronic hypoglycemia.

PMID- 11288763
TI  - Progesterone organogel for premenstrual dysphoric disorder.

PMID- 11288764
TI  - Porgesterone organogel for premenstrual dysphoric disorder.

PMID- 11288765
TI  - Cognitive changes during topiramate therapy.

PMID- 11288766
TI  - SSRI and mirtazapine in PTSD.

PMID- 11288767
TI  - Validity of structured clinical evaluations in adolescents with conduct and
      substance problems.
AB  - OBJECTIVE: To determine discriminative and convergent validity for certain
      structured diagnostic assessments among adolescents with conduct and substance
      problems. METHOD: Patients were 87 adolescents (both genders) in treatment for
      conduct and substance problems. Most controls (n = 85; both genders) came from
      patients' neighborhoods. Assessments included Diagnostic Interview Schedule for
      Children, Composite International Diagnostic Instrument-Substance Abuse Module,
      Child Behavior Checklist, and others. Patients' data guided clinical care.
      RESULTS: Youths' self-reports significantly discriminated patients from controls
      in DSM-IVconduct and substance use disorders (CD, SUD) and in numerous associated
      measures. CD and SUD symptoms correlated strongly. However, some patients
      apparently minimized symptoms. Youths' self-reports did not discriminate patients
      from controls in attention-deficit/hyperactivity disorder (ADHD) or major
      depression (MDD). Parent information raised prevalence rates of ADHD and MDD,
      which then discriminated patients from controls. However, patients and parents
      usually disagreed on MDD and ADHD diagnoses. CONCLUSIONS: Despite some
      dissimulation, patients' self-reports of CD and SUD correlated highly and had
      superb discriminative validity, making them useful for treatment and research.
      Self-reports of ADHD and MDD, apparently lacking discriminative validity, are
      less useful. Parent reports improve these discriminations but present additional
      problems.

PMID- 11288768
TI  - Predictors of engagement in adolescent drug abuse treatment.
AB  - OBJECTIVES: To identify key demographic, parent, and adolescent characteristics
      that influence engagement in outpatient drug abuse treatment. METHOD: Youths aged
      12 to 17 years (N = 224; 81% male and 72% African American) referred for drug
      treatment and their parents participated in this study. Marijuana was the primary
      substance of abuse. Data were gathered prior to treatment on demographic
      variables as well as on both parent and youth perspectives on youth, parent, and
      family functioning. RESULTS: A discriminant function analysis revealed that
      engagement in treatment was related to, in order of weighting, more positive
      parental expectations for their adolescent's educational achievement
      (standardized discriminant function coefficient [SDF] = 0.68), higher parental
      reports of youth externalizing symptoms (SDF = 0.59), and higher levels of family
      conflict perceived by the youth (SDF = 0.36). Family income, gender, juvenile
      justice status, minority group status, family structure, parental age and
      psychopathology, and treatment characteristics did not distinguish treatment
      engaged from unengaged adolescents. CONCLUSIONS: The results suggest that both
      parent and youth perceptions are pivotal to whether or not adolescents are
      engaged in psychotherapy. These findings lead the authors to recommend adolescent
      engagement interventions focusing on both the youth and his or her parents and
      suggest a content focus for adolescent engagement interventions.

PMID- 11288769
TI  - Child maltreatment: risk of adjustment problems and dating violence in
      adolescence.
AB  - OBJECTIVE: To examine the relationship between child maltreatment, clinically
      relevant adjustment problems, and dating violence in a community sample of
      adolescents. METHOD: Adolescents from 10 high schools (N= 1,419; response rate =
      62%) in southwestern Ontario completed questionnaires that assessed past
      maltreatment, current adjustment, and dating violence. Logistic regression was
      used to compare maltreated and nonmaltreated youths across outcome domains.
      RESULTS: One third (n = 462) of the school sample reported levels of maltreatment
      above the cutoff score on the Childhood Trauma Questionnaire. Girls with a
      history of maltreatment had a higher risk of emotional distress compared with
      girls without such histories (e.g., odds ratios [OR] for anger, depression,
      anxiety, and posttraumatic stress-related problems were 7.1, 7.2, 9.3, and 9.8,
      respectively). They were also at greater risk of violent and nonviolent
      delinquency (OR = 2.7) and carrying concealed weapons (OR = 7.1). Boys with
      histories of maltreatment were 2.5 to 3.5 times as likely to report clinical
      levels of depression, posttraumatic stress, and overt dissociation as were boys
      without a maltreatment history. They also had a significantly greater risk of
      using threatening behaviors (OR = 2.8) or physical abuse (OR = 3.4) against their
      dating partners. CONCLUSIONS: Maltreatment is a significant risk factor for
      adolescent maladjustment and shows a differential pattern for male and female
      adolescents.

PMID- 11288770
TI  - Patterns of remission and symptom decline in conduct disorder: a four-year
      prospective study of an ADHD sample.
AB  - OBJECTIVE: To evaluate systematically the longitudinal course of conduct disorder
      (CD) in a sample of youths with attention-deficit hyperactivity disorder (ADHD)
      to determine the effects of a persistent course on outcome. METHOD: One hundred
      forty children with ADHD and their nuclear families were assessed at baseline and
      again at 1 and 4 years. Subjects were examined by means of DSM-III-R-based
      structured interviews. They were also evaluated for cognitive and social
      functioning. Persistent (exhibiting symptoms of CD at either follow-up) and
      desistent (symptoms of CD at neither follow-up) cases were identified. RESULTS:
      Forty-two percent of CD cases followed a persistent course. Although both
      persistent and desistent subjects had high rates of antisocial disorders in
      relatives, increased family conflict and decreased family cohesion were
      selectively associated with a persistent course. In addition, subjects with
      persistent symptoms of CD exhibited more impaired ratings on the Aggression and
      Delinquency subscales of the Child Behavior Checklist, as well as higher rates of
      bipolar, oppositional defiant, and substance use disorders. CONCLUSIONS: These
      findings suggest that the poor prognosis associated with CD is limited to an
      identifiable subgroup with a persistent course.

PMID- 11288771
TI  - An investigation of female adolescent twins with both major depression and
      conduct disorder.
AB  - OBJECTIVE: Conduct disorder (CD) and major depression (MDD) frequently co-occur
      in adolescents, but little is known about the characteristics and functioning of
      youths, especially females, with both disorders. This study describes the
      functioning of female adolescents with histories of both CD and MDD. METHOD:
      Subjects were selected from an epidemiological sample of 17-year-old female twins
      based on having a lifetime DSM-III-R diagnosis of MDD and/or CD; control subjects
      had no history of either disorder. RESULTS: In nearly all domains examined,
      including measures of academic success (including academic achievement and school
      adjustment), personality, quality of peer relationships, and high-risk behavior
      (including substance dependence and early sexual experience), main effects of one
      or both disorders were found and related to impaired functioning. In addition,
      interaction effects were found in the areas of substance dependence symptoms (for
      all classes of substances), negative school-related events, and a personality
      based predisposition not to experience positive emotions, indicating that those
      with both diagnoses were especially impaired. CONCLUSIONS: In some domains,
      histories of MDD and CD interact and relate to particularly severe problems. The
      implications of these findings for research and treatment, including the high
      likelihood of substance and school adjustment problems in these youths, are
      discussed.

PMID- 11288772
TI  - Bupropion sustained release in adolescents with comorbid attention
      deficit/hyperactivity disorder and depression.
AB  - OBJECTIVE: To determine whether bupropion sustained release (SR) is effective and
      well-tolerated in adolescents with comorbid attention-deficit/hyperactivity
      disorder (ADHD) and depression. METHOD: Subjects were 24 adolescents (aged 11-16
      years old) with ADHD and either major depressive disorder or dysthymic disorder.
      After a 2-week, single-blind placebo lead-in, subjects were treated for 8+ weeks
      with bupropion SR at doses flexibly titrated up to 3 mg/kg b.i.d. (mean final
      doses: 2.2 mg/kg q A.M. and 1.7 mg/kg q P.M.). Outcomes were global improvement
      in ADHD and depression (clinician-rated), along with changes in depressive
      symptomatology (parent- and child-rated), ADHD symptomatology (parent- and
      teacher-rated), and functional impairment (parent-rated). RESULTS: Clinicians
      rated 14 subjects (58%) responders in both depression and ADHD, 7 (29%)
      responders in depression only, and 1 (4%) a responder in ADHD only. Compared with
      post-placebo ratings, final parents' (p < .0005) and children's (p = .016)
      ratings of depressive symptomatology improved significantly, as did parents' (p <
      .0005) but not teachers' (p = .080) ratings of ADHD symptomatology. Final ratings
      of functional impairment improved significantly from enrollment (p < .0005). No
      subject discontinued medication because of side effects. CONCLUSIONS: Bupropion
      SR may be effective and well-tolerated in adolescents with comorbid ADHD and
      depressive disorders. However, randomized, placebo-controlled studies are needed.

PMID- 11288773
TI  - Measuring outcomes of care for adolescents with emotional and behavioral
      problems.
AB  - OBJECTIVES: To validate the prototype Adolescent Treatment Outcomes Module
      (ATOM), examine its sensitivity to clinical change, and determine its feasibility
      for administration in routine clinical settings. METHOD: A sample of 67
      adolescents, aged 11 through 18, was selected from new patients at two inpatient
      and two outpatient mental health programs. Adolescents and parents completed the
      ATOM and validating instruments at intake, 1 week postintake, and again at 6
      months. RESULTS: Nine self-report symptoms predicted positive diagnoses of
      oppositional defiant, conduct, anxiety, and depressive disorders on the basis of
      structured diagnoses, with sensitivities of 0.7 to 0.8. Test-retest correlations
      for outcome scales were largely excellent (>0.70). Scales that measured
      functioning at home, in school, and in the community were moderately correlated
      in the expected direction with global functioning. Decreases in symptom severity
      and functional impairment were generally associated with decreases in validating
      instruments. Administration time averaged 25 minutes for adolescents and 28
      minutes for parents. CONCLUSIONS: Both parents and adolescents readily completed
      the ATOM. Module scales demonstrated excellent reliability and good to fair
      concurrent validity. The ATOM was able to detect change and its absence.

PMID- 11288774
TI  - Health gain and outcome predictors during inpatient and related day treatment in
      child and adolescent psychiatry.
AB  - OBJECTIVE: To investigate health gain and its predictors during inpatient and
      associated day patient treatment. METHOD: Consecutive admissions to two inpatient
      units for children and young adolescents in northwest England were studied (N =
      55). Ascertainments were made from multiple perspectives, including family,
      teacher, clinician, and an independent researcher. Measures were taken at
      referral, admission, discharge, and 6-month follow-up; health gain was inferred
      from change scores on measures. Recruitment lasted from late 1995 to 1997; follow
      up was completed during 1998. Independent variables tested as predictors included
      assessments of presenting symptoms, therapeutic alliance, and family functioning.
      RESULTS: Significant health gain during hospitalization was found on most
      measures and sustained to follow-up. There was no symptom change during the
      waiting-list control condition. Health gain was predicted independently by child
      and parental therapeutic alliance with the unit early in hospitalization and by
      preadmission family functioning. Externalizing problems did well if accompanied
      by good alliance. CONCLUSIONS: Assessment of health gain from multiple
      perspectives is possible and valuable. Inpatient treatment has significant
      therapeutic effect. Predictors for health gain lie in process variables of
      therapeutic alliance and family functioning rather than presenting symptoms. The
      results are discussed in relation to clinical practice and future research.

PMID- 11288775
TI  - The brief psychiatric rating scale for children (BPRS-C): validity and
      reliability of an anchored version.
AB  - OBJECTIVE: Because the accuracy of problems reported by referred children may be
      compromised by their academic, cognitive, or motivational limitations, clinician
      rating forms may contribute to the accurate assessment of youth adjustment. One
      such measure, the 21-item Brief Psychiatric Rating Scale for Children (BPRS-C),
      received psychometric study to estimate its potential contribution to the
      measurement of symptom dimensions. BPRS-C reliability and concurrent validity
      were calculated for youths who were receiving psychiatric services within a
      medical school department. METHOD: Five hundred forty-seven children aged 3 to 18
      years were rated by faculty or trainees; a subsample of 90 was concurrently rated
      by two observers. BPRS-C psychometric performance was demonstrated through
      interrater agreement, factor analysis, and multivariate analyses of variance
      across seven diagnosis-based groups. RESULTS: Although items and scales
      demonstrated substantial reliability and concurrent validity, item factor
      analysis revealed a few apparent errors in item-to-scale assignment. These errors
      were minimized by the use of three new second-order factor-derived scales:
      Internalization, Developmental Maladjustment, and Externalization. CONCLUSIONS:
      The BPRS-C can be easily integrated into academic clinical practice and is a
      reliable and valid method of child description. Additional study of three new
      BPRS-C factor scales and the application of the BPRS-C to the quantification of
      clinician observation of child symptomatic status are warranted.

PMID- 11288776
TI  - Scaling structured interview data: a comparison of two methods.
AB  - OBJECTIVE: Although structured interviews are currently considered essential
      assessment strategies for conducting research, the data they generate are
      typically not used for purposes beyond making categorical determinations about
      diagnoses. Because of the need for dimensional scales to be used in conjunction
      with categorical data, two dimensional scales constructed from structured
      interviews are presented and examined. One scale, Behavior, Anxiety, Mood, and
      Other (BAMO), provides an overall score by summing the percentage of symptoms
      endorsed for each of 20 behavior, anxiety, mood, and other disorders found in the
      Diagnostic Interview for Children and Adolescents-Revised (DICA-R, DSM-III-R
      version). Another scale, DICA-SUM, is constructed by summing all endorsed
      symptoms on the interview. In this study the psychometric and pragmatic
      characteristics of BAMO and DICA-SUM are compared. METHOD: Data were obtained
      from 570 children (331 bereaved, 110 depressed, 129 community) aged 5 to 18 years
      (mean +/- SD = 11.3 +/- 3.2) who were interviewed as part of an ongoing
      longitudinal childhood bereavement study from 1987 to 1996. RESULTS: Discriminant
      and convergent validity with other child psychopathology measures are comparable
      for BAMO and DICA-SUM. However, BAMO more clearly conveys information regarding
      the approximate number of diagnoses endorsed. CONCLUSION: This study identified
      two methods of creating dimensional scales from structured interviews. Use of
      such dimensional scales might allow for improved comparison of results across
      studies.

PMID- 11288777
TI  - Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive
      disorder: an exploratory SPECT study.
AB  - OBJECTIVE: Recent epidemiological and clinical data suggest that obsessive
      compulsive disorder (OCD) may be subtyped according the age of onset of obsessive
      compulsive symptoms. The regional cerebral blood flow (rCBF) single photon
      emission computed tomography (SPECT) technique was used to investigate whether
      the pathophysiology of OCD differs between early- and late-onset OCD subjects.
      METHOD: Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset
      (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF
      comparisons were performed with statistical parametric mapping. RESULTS: Early
      onset OCD cases showed decreased rCBF in the right thalamus, left anterior
      cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset
      subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls,
      early-onset cases had decreased left anterior cingulate and right orbitofrontal
      rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects
      showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus.
      In early-onset subjects only, severity of obsessive-compulsive symptoms
      correlated positively with left orbitofrontal rCBF. CONCLUSIONS: rCBF differences
      in frontal-subcortical circuits between early-onset and late-onset OCD subjects
      were found, both in location and direction of changes. These results provide
      preliminary evidence that brain mechanisms in OCD may differ depending on the age
      at which symptoms are first expressed.

PMID- 11288778
TI  - Motivational effects on inhibitory control in children with ADHD.
AB  - OBJECTIVE: The problems children with attention-deficit/hyperactivity disorder
      (ADHD) encounter in tasks measuring inhibitory control are often theoretically
      related to deficits in cognitive processes. This study investigated the effects
      of different motivational incentives on the ability of children to inhibit
      intended or ongoing actions. METHOD: In a large German industrial town, 33
      children with ADHD were compared with 33 members of a combined group of children
      with major depressive disorder, anxiety disorders, oppositional defiant disorder,
      or conduct disorder, and 33 children without any psychiatric disorder with
      respect to their performances in a stop-signal task. The children received
      continuous feedback under high- or low-incentive conditions. The children's
      performance was compared in terms of qualitative (inhibition rate) and
      quantitative (reaction time) measures. RESULTS: There were no indications of
      deficits in sustained attention in children with ADHD. Under conditions of low
      incentives, children with ADHD were less able to inhibit their reactions and had
      longer stop-signal reaction times. But when given high incentives, children with
      ADHD performed the task as well as both other groups. CONCLUSIONS: Supposed
      deficits in children with ADHD should be regarded from a perspective that
      differentiates performance from ability. Furthermore, the findings support a
      motivational explanation of the origins of lowered inhibitory control in children
      with ADHD.

PMID- 11288779
TI  - Predicting children's reported eating disturbances at 8 years of age.
AB  - OBJECTIVES: To examine differential parental influences on eating attitudes and
      behaviors of 8-year-old children with a specific focus on gender effects and to
      assess the specificity of this relationship. METHOD: One hundred eight infants
      were monitored from birth and interviewed at age 8 for eating disturbances and
      negative affect with an adaptation of the McKnight Risk Factor Survey. Parental
      measures included the Three Factor Eating Questionnaire subscales Disinhibition
      and Restraint as well as body mass index, assessed at study entry. RESULTS: No
      gender differences were found for frequencies of children's self-reported eating
      disturbances. Higher maternal restraint scores predicted worries about being too
      fat in girls but not in boys. Higher maternal disinhibition scores also
      differentially predicted weight control behaviors in their daughters. Negative
      affect in the child was (weakly) predicted by higher maternal body mass index. No
      association between paternal predictors of disturbed eating and the child's
      eating disturbances and negative emotionality was found. CONCLUSIONS: The impact
      of maternal eating disorders and disturbances is much stronger than that of
      fathers and is specifically directed at their daughters. The clinical importance
      of these disturbances in terms of precursors of adolescent eating disorders has
      to be determined by monitoring the sample through puberty.

PMID- 11288780
TI  - Case study: sexual hyperactivity treated with psychostimulants in familial male
      precocious puberty.
AB  - Familial male precocious puberty is a form of precocious puberty resulting from
      an activating mutation of the luteinizing hormone receptor. Behavior problems are
      associated with the early onset of puberty. In this case, sexual hyperactivity
      was treated with psychostimulants. Implications for the effectiveness of
      methylphenidate in reducing sexual hyperactivity with and without familial male
      precocious puberty are discussed, and testable hypotheses are proposed for the
      effects of stimulants on sexual behavior in adolescents.

PMID- 11288781
TI  - An innovative psychodynamically influenced approach to reduce school violence.

PMID- 11288782
TI  - Genetics of childhood disorders: XXIV. ADHD, part 8: hyperdopaminergic mice as an
      animal model of ADHD.

PMID- 11288783
TI  - Clinical comparison of bioactive glass bone replacement graft material and
      expanded polytetrafluoroethylene barrier membrane in treating human mandibular
      molar class II furcations.
AB  - BACKGROUND: Class II furcations present difficult treatment problems and
      historically several treatment approaches to obtain furcation fill have been
      used. METHODS: The response of mandibular Class II facial furcations to treatment
      with either bioactive glass (PG) bone replacement graft material or expanded
      polytetrafluoroethylene (ePTFE) barrier membrane was evaluated in 27 pairs of
      mandibular molars in 27 patients with moderate to advanced periodontitis.
      Following initial preparation, full thickness flaps were raised in the area being
      treated, the bone and furcation defects debrided of granulomatous tissue, and the
      involved root surfaces mechanically prepared and chemically conditioned. By
      random allocation, PG or ePTFE was placed into or fitted over the furcations,
      packed or secured in place, and the host flap replaced or coronally positioned
      with sutures. Postsurgical deplaquing was performed every 10 days leading up to
      ePTFE removal at about 6 weeks. Continuing periodontal maintenance therapy was
      provided until surgical reentry at 6 months for documentation and any further
      necessary treatment. RESULTS: Direct clinical measurements demonstrated
      essentially similar clinical results with both treatments for bone and soft
      tissue changes. There were no statistically or clinically significant differences
      (e.g., mean horizontal furcation fill 1.4 mm PG, 1.3 mm ePTFE; mean percent
      horizontal furcation fill 31.6% PG, 31.1% ePTFE, both P>0.85). Seventeen of the
      PG treated and 18 of the ePTFE furcations became Class I clinically and 1
      furcation completely closed clinically with each treatment. Intrapatient
      comparisons showed similar horizontal furcation responses with both treatments.
      CONCLUSION: The findings of this study suggest essentially equal clinical results
      with PG bone replacement graft material and e-PTFE barriers in mandibular molar
      Class II furcations. PG use was associated with simpler application and required
      no additional material removal procedures.

PMID- 11288784
TI  - Intra- and inter-examiner reproducibility in keratinized tissue width assessment
      with 3 methods for mucogingival junction determination.
AB  - BACKGROUND: Although the need for "adequate" amount of keratinized tissue (KT)
      for periodontal health is questionable, the mucogingival junction (MGJ) often
      serves as a measurement landmark in periodontal evaluations. Limited information
      is available on the reproducibility of KT width (KTW) assessment. The purpose of
      this study was to assess intra- and inter-examiner reproducibility in measuring
      KTW by using 3 different methods to identify MGJ location. METHODS: Fifteen
      patients provided 17 teeth which had undergone a gingival augmentation procedure
      (connective tissue graft; surgery group) and an equal number of contralateral,
      non-treated teeth (control group). At the midbuccal aspect of each tooth, KTW was
      assessed by 2 independent examiners after MGJ identification by the visual (VM),
      functional (FM), and visual with histochemical staining (HM) method. Data
      analysis was based on intra-class correlation coefficients (ICC) and 3-way
      analysis of variance (ANOVA) for differences between replicate measurements.
      RESULTS: KTW was significantly different between treated and control teeth. No
      significant differences in KTW were found in relation to method for MGJ
      determination and examiner. Intra- and inter-examiner reproducibility was high,
      regardless of treatment status or method for MGJ determination (ICC = 0.92 -
      0.99). Standard deviations of the difference between replicate measurements
      ranged from 0.46 mm for VM to 0.21 mm for HM. CONCLUSIONS: Intra- and inter
      examiner reproducibility has been shown to be substantially consistent when
      different methods for MGJ determination are used to measure the apico-coronal
      dimension of the gingiva. The level of reproducibility does not seem to be
      affected whether or not the mucogingival complex has been surgically altered by a
      gingival augmentation procedure.

PMID- 11288785
TI  - The influence of partial and full-mouth recordings on estimates of prevalence and
      extent of lifetime cumulative attachment loss: a study in a population of young
      male military recruits.
AB  - BACKGROUND: Previous studies have shown that the use of index teeth may
      underestimate the prevalence of chronic periodontitis in adults. However, there
      is little information on the effect of using index teeth to estimate the
      prevalence of early periodontitis in younger adults and the effect this may have
      on planning treatment needs and health care resources. The aim of this study was
      to compare full mouth examination with partial examination using index teeth in a
      group of young British males. METHODS: One hundred subjects aged between 16 and
      20 years (mean 17 years) on entry to the study were examined at baseline, 12
      months later, and 30 months later. Lifetime cumulative attachment loss (LCAL) >
      or =1 mm was measured on the mesio-buccal, disto-buccal, mesio-lingual, and disto
      lingual surfaces of all teeth, excluding third molars. All data were entered into
      a database. The indices used to express LCAL were prevalence, defined as the
      percentage of subjects with LCAL > or =1 mm, 2 mm, or 3 mm, and extent, defined
      as the percentage of sites with LCAL > or =1 mm, 2 mm, or 3 mm. Two sets of index
      teeth were chosen to compare with full mouth recordings, Ramfjord index teeth and
      the Periodontal Index for Treatment (PIT) teeth. RESULTS: The prevalence of LCAL
      > or =1 mm was similar (approaching 100%) for the full mouth and both partial
      mouth recordings. However, as LCAL increased from a minimum of 1 to 3 mm, partial
      mouth recording resulted in an underestimation of the prevalence of disease. LCAL
      > or =2 mm was underestimated by up to 22% and LCAL > or =3 mm by up to 36%. The
      extent of LCAL was less affected by partial mouth recording, in that the
      percentage of sites with no sign of early attachment loss was underestimated by
      up to 11%. However, the percentage of sites with LCAL > or =1 mm and 2 mm were
      overestimated by 11% and, 7% respectively. CONCLUSIONS: These data indicate that
      the use of index teeth in epidemiological studies which include young adults may
      result in an underestimation of the prevalence of early periodontitis and an
      overestimation of the extent.

PMID- 11288786
TI  - Systemic neutrophil response resulting from dental plaque accumulation.
AB  - BACKGROUND: There is considerable current interest in putative relationships
      between oral and systemic diseases. Since the host response to oral bacteria may
      be the critical link in this association, our hypothesis was that dental plaque
      accumulation in healthy subjects would elicit a systemic inflammatory response.
      METHODS: Twenty-three healthy subjects, aged 18 to 25, participated in a 4-phase
      study. An initial hygiene phase was followed by a 21-day experimental phase (the
      so-called experimental gingivitis model) in which subjects refrained from all
      oral hygiene practices, thus permitting the accumulation of bacterial plaque. At
      days 0, 7, and 21 total and differential peripheral white blood cell (wbc)
      counts, together with full mouth plaque and gingivitis scores, were recorded.
      Following a 28-day recovery phase, in which normal oral hygiene practices were
      resumed, subjects entered the final 21-day control phase which mirrored the
      experimental phase but with subjects maintaining normal oral hygiene practices.
      RESULTS: The experimental model performed as anticipated with a correlation
      between plaque and gingivitis scores of 0.95, also reflecting subject compliance.
      Total wbc and neutrophil counts increased during the experimental phase.
      Furthermore, comparison of neutrophil counts between the experimental and control
      phases demonstrated a significantly higher cell count for the experimental phase
      on both days 7 and 21 (P= 0.0301 and 0.009, respectively). For total wbc, this
      was significant on day 21 (P= 0.0262). CONCLUSION: The results of this study
      support the hypothesis that the accumulation of dental plaque can result in a
      measurable systemic inflammatory response, providing further in vivo data to
      support a mechanistic relationship between oral and systemic pathology.

PMID- 11288787
TI  - Porous bovine bone mineral in healing of human extraction sockets: 2.
      Histochemical observations at 9 months.
AB  - BACKGROUND: Porous bovine bone mineral (PBBM) has been used in ridge preservation
      procedures following tooth extractions. The aim of this study was to investigate
      histochemically tissue sockets grafted with PBBM at 9 months post-extraction. By
      using different histochemical stainings, characteristics of the newly formed
      bone; i.e., lamellar/woven ratio at different socket depths, were investigated
      and the arrangement of bone around the grafted material, as well as the nature of
      the amorphous organic material found in all specimens, were examined. METHODS:
      After extraction of 15 single-rooted maxillary teeth from 15 patients, socket
      sites were grafted with PBBM particles (250 to 1,000 mu). Primary soft tissue
      closure of the grafted site was established using the rotated split palatal
      pedicle flap technique. At 9 months, a cylindrical tissue specimen, 2.5 mm in
      diameter, was trephined from each previously grafted site followed by placement
      of a screw-shaped implant. Horizontal tissue section cuts, 5 mu wide, were
      prepared for histological examination. Histochemical staining included alcian
      blue, periodic-acid Schiff, Mallory trichrome, reticulin, Van Gieson, and
      picrosirius red (PSR). PSR stained slides were further evaluated
      morphometrically, using polarized microscopy to determine the amount of lamellar
      versus woven bone in superficial, mid and deep specimen section cut areas.
      RESULTS: All staining methods revealed that newly formed bone encircled and
      adhered to the grafted material in most specimens. Mallory trichrome staining
      showed osteoblasts present within an osteoid layer, lining the interface zone of
      PBBM particles and the new osseous tissue. Morphometric evaluation of the PSR
      stained slides disclosed a constant pattern of increased osseous tissue in a
      coronal-apical direction. An average of 17.1% osseous tissue with 1:12.9
      lamellar/woven bone ratio was calculated in the superficial area. The average
      bone tissue fraction was 48.3% with a lamellar/woven ratio of 1:3.8 in the mid
      section area and in the deep area, it increased to 63.9%, with a lamellar/woven
      ratio average of 1:1.7. Differences between ratios at these sites were
      statistically significant (P<0.001). An amorphous organic substance was noted in
      most grafted particles. This material usually attached cell striae and harbored
      glycoproteins as revealed by periodic-acid Schiff and alcian blue stainings.
      Mallory trichrome staining showed denatured protein within the decalcified
      mineral particles; reticulin, Van Gieson stainings, and polarization of PSR
      stained sections refuted the existence of collagen in the grafted particles.
      CONCLUSIONS: Cancellous PBBM is a biocompatible filler agent in extraction socket
      sites and an acceptable graft for edentulous ridge preservation at sites prepared
      to receive endosseous implants. The osteoconductivity of PBBM was determined
      based on promoting osseous ingrowth and close integration with the newly
      generated bone. Grafted particles were not significantly resorbed at 9 months.
      Further studies are needed to determine the resorbable capability, as well as the
      nature and significance of the amorphous organic substance of PBBM observed in
      the grafted particles.

PMID- 11288788
TI  - Macrophages and lymphocyte subpopulations in nifedipine- and cyclosporin A
      associated human gingival overgrowth.
AB  - BACKGROUND: Nifedipine and cyclosporin A (CsA) induce gingival overgrowth. Both
      drugs have immunomodulating effects. It has been suggested that altered immune
      response is associated with drug-induced gingival overgrowth. In this study, we
      evaluated whether there were differences in macrophages and lymphocyte
      subpopulations in human nifedipine- and CsA-associated gingival overgrowth as
      compared with those in normal gingiva. METHODS: Biopsy samples of overgrown
      gingiva were obtained from 9 nifedipine-treated cardiac outpatients, 13 CsA
      treated renal transplant recipients including 9 patients who were also receiving
      nifedipine, and 30 healthy control individuals undergoing dental treatment.
      Serial 5 microm thick cryostat sections were stained with mAbs for CD20 (B-pan),
      CD68 (macrophages), CD4 (T-helper/inducer), and CD8 (T-cytotoxic/suppressor)
      using an avidin-biotin-horseradish peroxidase complex method. Numbers of mAb
      labeled and all nucleated cells were determined in 3 areas: the connective tissue
      beneath the sulcular epithelium, the middle connective tissue, and the connective
      tissue beneath the oral epithelium. Distributions of each type of cell were
      expressed as percentages of mAb-labeled cells in relation to total number of
      nucleated cells in a counting zone. Significances of differences between groups
      were tested by means of the Kruskal-Wallis test, and between pairs of results by
      means of the Mann-Whitney U-test. RESULTS: The proportion of CD8-labeled cells
      was significantly higher in connective tissue beneath the sulcular epithelium in
      the nifedipine group than in the controls (P = 0.014). In both medicated groups,
      the proportions of CD68-labeled cells were higher in all counting zones than in
      the controls, but statistically significantly only in the nifedipine group in the
      connective tissue beneath the oral epithelium (P = 0.008). No intergroup
      differences were found with respect to CD4- and CD20-labeled cells. The CD4/CD8
      ratio was significantly lower in connective tissue beneath the sulcular
      epithelium in the nifedipine group than in the controls (P= 0.013). CONCLUSION:
      The results support the idea that immune response may be altered in drug-induced
      gingival overgrowth.

PMID- 11288789
TI  - Mitotic activity of keratinocytes in nifedipine- and immunosuppressive medication
      induced gingival overgrowth.
AB  - BACKGROUND: The purpose of the study was to compare mitotic activity in the basal
      cell layer of normal human gingiva and in nifedipine- and immunosuppressive
      medication-induced gingival overgrowth. METHODS: Gingival samples were collected
      from 19 generally healthy individuals, 12 nifedipine-medicated cardiac patients,
      and 22 immunosuppression-medicated (azathioprine, prednisolone, and cyclosporin
      A) organ transplant recipients. The transplant recipients were divided into those
      not taking nifedipine and those taking nifedipine. Cryostat sections were stained
      with monoclonal antibody for Ki-67, using an avidin-biotin-enzyme complex method.
      The mitotic activities of epithelial cells were determined as percentages of Ki
      67 labeled cells in relation to total numbers of epithelial cells in the basal
      layer of oral, oral sulcular, and sulcular epithelium. RESULTS: Mitotic
      activities were significantly higher in all 3 medication groups in the oral
      epithelium (P < or =0.003), and in the immunosuppression group in the sulcular
      epithelium (P= 0.032) than in the controls. In the oral sulcular epithelium,
      mitotic activity was fairly similar in all medication groups. In the nifedipine
      group a significant negative correlation was found between duration of nifedipine
      medication and the percentage of Ki-67 labeled cells in the oral epithelium (P=
      0.025). CONCLUSIONS: The results suggest that the increased epithelial thickness
      observed in nifedipine- and cyclosporin A-induced gingival overgrowth is
      associated with increased mitotic activity, especially in the oral epithelium.

PMID- 11288790
TI  - Laser irradiation of bone: III. Long-term healing following treatment by CO2 and
      Nd:YAG lasers.
AB  - BACKGROUND: Relative few reports exist concerning healing of laser created
      osteotomies over an extended period of time. The purpose of this study was to
      evaluate long-term healing, from 21 to 63 days, of osteotomy defects in the rat
      tibia created with the Nd:YAG and CO2 in the presence of a surface cooling spray
      of air/water. METHODS: The experimental model consisted of 15 large Sprague
      Dawley rats. Six treatment modalities were randomly distributed among 6 tibial
      recipient sites: 1) a negative control (no treatment); 2) a positive control (bur
      osteotomy); 3) CO2 laser at 5 W (860 J/cm2); 4) CO2 laser at 6 W (1,032 J/cm2);
      5) Nd:YAG laser at 5 W (714 J/cm2); and 6) Nd:YAG laser at 7 W (1,000 J/cm2). All
      laser irradiation was delivered in the presence of a surface coolant consisting
      of air (15 psi) and sterile water. Five animals were sacrificed at each of 3 time
      intervals: 21, 35, and 63 days post-treatment. Multiple histologic sections from
      each treatment site were examined by light microscopy using hematoxylin and eosin
      Goldner's trichrome stains, and polarized light and evaluated for presence of a
      char layer, heat induced cracking, heat related alterations in cells or tissue
      matrix, and osseous regeneration. RESULTS: Healing was severely delayed in all
      laser treated sites compared to positive control sites. Of the laser treated
      sites, those irradiated by CO2 laser at 5 W (780 J/cm2) exhibited the greater
      amount of bone regeneration. At best, however, only a small percentage of
      sections from any of the laser treated specimens showed evidence of bone
      regeneration within the ablation defect regardless of the post-treatment time
      interval. CONCLUSIONS: Under the conditions of this study, the osseous healing
      response was severely delayed by CO2 and Nd:YAG laser irradiation of bone, even
      in the presence of a surface cooling spray of air/water.

PMID- 11288791
TI  - The effect of alcohol consumption on periodontal disease.
AB  - BACKGROUND: Alcohol consumption, like smoking, may be related to periodontal
      disease independently of oral hygiene status. This study assessed the
      relationship between alcohol consumption and severity of periodontal disease.
      METHODS: A cross-sectional study of 1,371 subjects ages 25 to 74 in the Erie
      County, NY population was performed. Alcohol intake was assessed by means of
      previously validated self-reported questionnaires. Outcome variables were
      gingival bleeding, clinical attachment loss, alveolar bone loss, and presence of
      subgingival microorganisms. RESULTS: Logistic regression analyses adjusting for
      age, gender, race, education, income, smoking, diabetes mellitus, dental plaque,
      and presence of any of 8 subgingival microorganisms showed that those consuming >
      or =5 drinks/week had an odds ratio (OR) of 1.65 (95% CI: 1.22 to 2.23) of having
      higher gingival bleeding, and OR of 1.36 (95% CI: 1.02 to 1.80) of having more
      severe clinical attachment loss compared to those consuming <5 drinks/week. Those
      consuming > or =10 drinks/week had an odds ratio (OR) of 1.62 (95% CI: 1.12 to
      2.33) of having higher gingival bleeding and OR of 1.44 (95% CI: 1.04 to 2.00) of
      having more severe clinical attachment loss compared to those consuming <10
      drinks/week. Alcohol consumption was not significantly related to alveolar bone
      loss nor to any of the subgingival microorganisms. CONCLUSIONS: The results
      suggest that alcohol consumption is associated with moderately increased severity
      of periodontal disease. Longitudinal studies are needed to determine whether
      alcohol is a true risk factor for periodontal disease.

PMID- 11288792
TI  - The effect of postsurgical antibiotics on the healing of intrabony defects
      following treatment with enamel matrix proteins.
AB  - BACKGROUND: Regenerative treatment with enamel matrix proteins has been shown to
      promote healing in intrabony defects. However, up to now various postoperative
      antibiotic regimens have been used in combination with enamel matrix proteins and
      therefore it cannot be excluded that the results may also be attributable to the
      effect of the antibiotic treatment. The aim of this randomized, controlled,
      blinded, clinical investigation was to determine the effect of postsurgical
      administration of antibiotics on the healing of intrabony periodontal defects
      treated with enamel matrix proteins. METHODS: Thirty-four patients each of whom
      exhibited one deep intrabony defect were randomly treated with either enamel
      matrix proteins plus antibiotics (test: EMD + AB) or with enamel matrix proteins
      alone (control: EMD). The antibiotic regimen consisted of a combination of 3 x
      375 mg amoxicillin and 3 x 250 mg metronidazole daily for 7 days. The following
      parameters were recorded at baseline and at 1 year by the same calibrated and
      blinded investigator: plaque index (PI), gingival index (GI), bleeding on probing
      (BOP), probing depth (PD), gingival recession (GR), and clinical attachment level
      (CAL). Power analysis to determine superiority of antibiotic treatment showed
      that the available sample size would yield 85% power to detect a 1 mm difference.
      RESULTS: No statistically significant differences in any of the investigated
      parameters between the 2 groups were observed at baseline. No serious adverse
      events such as allergic reactions or abscesses after any of the treatments were
      observed during the entire study period. The results have shown that in the EMD +
      AB group the PD decreased from 9.1 +/- 1.5 mm to 4.5 +/- 1.1 mm (P<0.0001) and
      the CAL changed from 11.0 +/- 1.6 mm to 7.5 +/- 1.4 mm (P<0.0001). In the EMD
      group the PD decreased from 9.0 +/- 1.7 mm to 4.3 +/- 1.7 mm (P <0.0001) and the
      CAL changed from 10.6 +/- 1.6 mm to 7.3 +/- 1.5 mm (P <0.0001). There were no
      significant differences in any of the investigated parameters between the 2
      groups. CONCLUSIONS: It can be concluded that the systemic administration of
      amoxicillin and metronidazole adjacent to the use of EMD for the surgical
      treatment of intrabony periodontal defects does not produce statistically
      superior PD reduction and CAL gain when compared to treatment with EMD alone.
      Hence, the present results do not support the routine administration of
      amoxicillin and metronidazole following regenerative treatment with EMD.

PMID- 11288793
TI  - Practice management: observations, issues, and empirical evidence.
AB  - BACKGROUND: The primary objective of this study is to provide objective,
      empirical, evidence-based practice management information. This is a hitherto
      under-researched area of considerable interest for both the practitioner and
      educator. METHODS: A questionnaire eliciting a mix of structured and free text
      responses was administered to a random sample of 480 practitioners who are
      members of the American Academy of Periodontology. Potential respondents not in
      private practice were excluded and the next listed person substituted. RESULTS:
      The results provide demographic and descriptive information about some of the
      main issues and problems facing practice managers, central to which are
      information technology (IT), financial, people management, and marketing. Human
      resource and marketing management appear to represent the biggest challenges.
      CONCLUSIONS: Periodontists running practices would prefer more information,
      development, and support in dealing with IT, finance, marketing, and people
      management. The empirical evidence reported here suggests that although tailored
      educational programs on key management issues at both undergraduate and
      postgraduate levels have become ubiquitous, nevertheless some respondents seek
      further training opportunities. Evidence-based practice management information
      will be invaluable to the clinician considering strategic and marketing planning,
      and also for those responsible for the design and conduct of predoctoral and
      postdoctoral programs.

PMID- 11288794
TI  - Clinical and radiological improvement of periodontal disease in patients with
      type 2 diabetes mellitus treated with alendronate: a randomized, placebo
      controlled trial.
AB  - BACKGROUND: Alendronate (ALN) is an aminobisphosphonate commonly used for
      osteoporosis in postmenopausal women. We studied the effect of ALN on bone loss
      prevention in type 2 diabetes mellitus patients with periodontal disease.
      METHODS: In a controlled double-blind, randomized study we evaluated
      prospectively diabetic patients paired by gender and years since diagnosis for 6
      months. The study included 40 patients (20 men and 20 women), 50 to 60 years old,
      with more than 5 years since diagnosis of diabetes and established periodontitis.
      They were randomly allocated to alendronate (10 mg/daily) or placebo treatment
      for 6 months. The endpoints of treatment were: the distance between the alveolar
      bone border and the cemento-enamel-junction (CEJ) evaluated by means of digital
      radiographic imaging, a biochemical marker of bone resorption (urine N
      telopeptide) (Ntx), and periodontal parameters. Metabolic control was assessed at
      baseline and after 6 months. RESULTS: Baseline and 6-month glycated hemoglobin
      levels were similar in both groups. Alendronate induced a significant decrease in
      NTx at 6 months (P = 0.006). Periodontal parameters improved in both groups.
      However, they were significantly better for the ALN treated group. Alveolar bone
      border-CEJ distance increased in the placebo, but decreased in the ALN group (P =
      0.0003). CONCLUSIONS: In type-2 diabetic patients, alendronate induced more
      improvement in alveolar bone crest height than control therapy. No differences in
      urinary N-telopeptide or glycated hemoglobin were observed in this short-term
      randomized controlled pilot trial.

PMID- 11288795
TI  - Bacteremia due to periodontal probing: a clinical and microbiological
      investigation.
AB  - BACKGROUND: Infective endocarditis can occur in susceptible individuals due to
      bacteremia of oral origin. The aim of this study was to investigate the
      occurrence of bacteremia caused by full mouth periodontal probing. METHODS: Forty
      patients, 20 with adult periodontitis (10 males, 10 females; mean age 43.0 years)
      and 20 with chronic gingivitis (11 males, 9 females; mean age 35.5 years) were
      investigated. Prior to and immediately following periodontal probing, 20 mL of
      venous blood were obtained from each patient and inoculated into aerobic and
      anaerobic blood culture bottles and incubated. Negative bottles were monitored
      continuously for 3 weeks before being discarded. Bottles which signalled positive
      were subcultured and isolates identified to genus level. Periodontal probing
      consisted of measuring pockets at 6 points around each tooth and recording the
      presence or absence of bleeding. A plaque index (PI) was assessed on the 6
      Ramfjord teeth. RESULTS: Probing caused bacteremia of oral origin in 8 (40%) of
      the periodontitis patients and 2 (10%) of the gingivitis patients. Streptococcus
      spp. were the most common isolates in both groups. Compared with the gingivitis
      group the odds ratio (OR) for bacteremia in the periodontitis group was 5.993
      (95% CI 1.081 to 33.215). Bleeding on probing (OR 1.025, 95% CI 1.004 to 1.047)
      and mean probing depth per tooth (OR 1.444, 95% CI 1.055 to 1.977) were
      significantly associated with bacteremia. No significant correlations were found
      between bacteremia and age, number of teeth probed, smoking status, PI, or total
      probing depth. CONCLUSIONS: Patients with untreated adult periodontitis are at
      greater risk of bacteremia due to periodontal probing than patients with chronic
      gingivitis. For individuals at risk of infective endocarditis, radiographic
      assessment prior to periodontal probing would be advisable to identify those with
      periodontitis so that appropriate antibiotic prophylaxis can be provided.

PMID- 11288796
TI  - Collagen membranes: a review.
AB  - Collagen materials have been utilized in medicine and dentistry because of their
      proven biocompatability and capability of promoting wound healing. For guided
      tissue regeneration (GTR) procedures, collagen membranes have been shown to be
      comparable to non-absorbable membranes with regard to probing depth reduction,
      clinical attachment gain, and percent of bone fill. Although these membranes are
      absorbable, collagen membranes have been demonstrated to prevent epithelial down
      growth along the root surfaces during the early phase of wound healing. The use
      of grafting material in combination with collagen membranes seems to improve
      clinical outcomes for furcation, but not intrabony, defects when compared to the
      use of membranes alone. Recently, collagen materials have also been applied in
      guided bone regeneration (GBR) and root coverage procedures with comparable
      success rates to non-absorbable expanded polytetrafluoroethylene (ePTFE)
      membranes and conventional subepithelial connective tissue grafts, respectively.
      Long-term clinical trials are still needed to further evaluate the benefits of
      collagen membranes in periodontal and peri-implant defects. This article will
      review the rationale for each indication and its related literature, both in
      vitro and in vivo studies. The properties that make collagen membranes attractive
      for use in regenerative therapy will be addressed. In addition, varieties of
      cross-linking techniques utilized to retard the degradation rate of collagen
      membranes will be discussed.

PMID- 11288797
TI  - Esthetic management of multiple recession defects in a patient with cicatricial
      pemphigoid.
AB  - Cicatricial pemphigoid is one of a number of mucocutaneous disorders that can
      present in the oral cavity with desquamation, pain, and bleeding of the gingiva
      and oral mucosa. This case report describes the management of cicatricial
      pemphigoid in a patient with multiple sites of gingival recession using
      connective tissue grafting to alleviate root surface sensitivity and improve
      esthetics. The treatment rationale is presented and discussed in terms of timing
      of therapy and implications for wound healing in patients who present with
      desquamative gingivitis.

PMID- 11288798
TI  - Periodontal regeneration of a class II furcation defect utilizing a bioabsorbable
      barrier in a human. A case study with histology.
AB  - This case report describes human histologic data of periodontal regeneration
      following guided tissue regeneration therapy (GTR) with a bioabsorbable barrier
      composed of polylactic acid. The tooth that was examined was part of a previously
      published study of the clinical effects of GTR therapy without the use of bone or
      bone substitutes on Class II furcation defects. Twenty-five months following the
      surgical procedure, the tooth was extracted for non-periodontal reasons. During
      this extraction, the bone within the furcation that was treated in the study was
      luxated with the tooth. At the completion of the study (month 12), the
      furcation's vertical probing depth had decreased by 2 mm with a 2 mm gain in
      clinical attachment. The horizontal furcation measurement decreased by 3 mm.
      Following extraction, the tooth was prepared for light microscopy and sectioned
      in the mesial-distal plane. Reference notches were not placed in the tooth at the
      time of surgery as there were no plans to perform histologic analysis in the
      study. However, using the buccal root prominences and what we interpreted to be
      root planing marks on the cementum, we were able to demonstrate that complete
      periodontal regeneration occurred on the root surface that was exposed to the
      pocket environment prior to surgery. New alveolar bone, cementum, and periodontal
      ligament were consistently observed throughout the furcation in the areas that
      demonstrated clinical attachment gain and a decrease in horizontal probing depth.
      This case report adds to the accumulating evidence of histologic periodontal
      regeneration following guided tissue regeneration with bioabsorbable polylactic
      acid barriers.

PMID- 11288799
TI  - Immunopathological diagnosis of cicatricial pemphigoid with desquamative
      gingivitis. A case report.
AB  - Cicatricial pemphigoid (CP) is a chronic subepidermal bullous dermatosis which
      primarily involves the mucous membranes. The oral cavity and the eye are most
      frequently involved. Since extension of the lesion into the pharynx and esophagus
      causes sore throat and dysphagia and progressive ocular lesions may cause
      blindness, early and valid diagnosis is very important. Here we present a case of
      cicatricial pemphigoid with onset at age 45 in a patient who manifested severe
      periodontal disease and showed the lesion on the mucous membranes of the mouth
      (desquamative gingivitis), skin, and eyes. Since definite diagnosis is very
      important, we describe how we made a differential diagnosis from other diseases
      which also accompany desquamative gingivitis. We examined the clinical
      manifestations, blood test results, HLA-genotype, histopathologic findings of the
      affected tissue, and immunological findings in relation to autoimmunity. Since
      many of the CP cases are first referred to periodontists or dentists, we believe
      that the diagnostic strategy described in the present study will be quite
      informative for making rapid and definite diagnoses of similar cases.

PMID- 11288800
TI  - Guided bone regeneration for dehiscence and fenestration defects on implants
      using an absorbable polymer barrier.
AB  - BACKGROUND: Guided bone regeneration (GBR) using a non-absorbable barrier has
      provided clinicians the ability to place implants in sites compromised by
      insufficient bone, including immediate extraction sites. Recent evidence suggests
      that successful GBR outcomes may be possible using bioabsorbable polymer
      barriers. METHODS: This report presents a case series of 9 patients with 8
      fenestration and 3 dehiscence defects on implants consecutively treated with GBR.
      A bioabsorbable polymer barrier of poly(DL-lactide) was used in conjunction with
      a composite graft of freeze-dried bone allograft (FDBA)/demineralized freeze
      dried bone allograft (DFDBA) mixed in a ratio of 1:1. Second-stage surgeries were
      performed at 4 to 8.5 months (5. 7 months average) post-placement. Biopsy
      material from 2 sites was obtained while exposing the implant for healing
      abutment connection. RESULTS: Ten of the 11 defects (90.9%) achieved complete
      coverage of the osseous defects. Histologic evaluations revealed the formation of
      viable bone, frequently in close amalgamation with residual graft particles.
      CONCLUSION: These case reports suggest that a poly(DL-lactide) polymer can be
      used as a physical barrier with a composite bone replacement graft to achieve
      successful GBR results of dehiscence/fenestration defects when placing implants.

PMID- 11288801
TI  - Bioabsorbable materials for guided bone regeneration prior to implant placement
      and 7-year follow-up: report of 14 cases.
AB  - BACKGROUND: The purpose of the present study was to evaluate the efficacy of a
      guided bone regeneration (GBR) procedure prior to implant placement and the long
      term outcome of the inserted implants. METHODS: Prior to dental implant
      placement, GBR procedure was performed on 14 patients (mean age 48 years) using a
      synthetic hydroxyapatite (HA) spacer under a collagen membrane. After a mean
      healing period of 8 months, bone biopsies were obtained during the placement of
      14 implants. The specimens were processed for histology without demineralization
      in order to assess bone quality and quantity of the regenerated bone. RESULTS:
      Both the bone density and the resorption degree of HA particles were relatively
      varied between samples. The different phenotypes of osteoclasts and
      multinucleated giant cells and the individual host response could partially
      explain the unpredictable results in terms of bone remodeling and biomaterial
      resorption. However, the presence of HA particles in the regenerated bone had no
      influence on the osseointegration of implants presenting a success rate of 86%
      after a 7-year observation period. CONCLUSIONS: These results confirm the
      possibility of regenerating bone by means of bioabsorbable materials, assuring at
      the same time the long-term success for implants inserted in regenerated sites.

PMID- 11288802
TI  - Management of soft tissue ridge deformities with acellular dermal matrix.
      Clinical approach and outcome after 6 months of treatment.
AB  - BACKGROUND: Soft tissue ridge defects often hamper ideally shaped artificial
      crowns and are basically treated using autogenous soft tissue grafts or
      alloplastic materials. These approaches present disadvantages such as the
      necessity of creating additional surgical fields to harvest the graft and the
      requirement of primary closure, which may reduce ridge height. This investigation
      evaluated the use of acellular dermal matrix (ADM) in the treatment of soft
      tissue ridge defects. METHODS: Eight patients, non-smokers with non-contributory
      medical history, provided 18 sites corresponding to missing teeth in the anterior
      maxillary arch. The ideal horizontal gain (desired gain) was waxed up in study
      casts, which served as templates for construction of modified acrylic stents with
      orthodontic wires. These stents served as references for ideal horizontal gain
      and also as fixed reference points for further evaluation. The distance from the
      orthodontic wire to the buccal plate of the defect also represented its baseline
      horizontal component. Vertical variations were evaluated with another stent and,
      in this case, no desired gain was considered. After raising partial-thickness
      flaps, the ADM material was rehydrated and folded to fill the defect and
      reproduce the desired gain. Flaps were sutured with no tension, and part of the
      material was intentionally left exposed to avoid pressure on the incision line
      and prevent height loss. Patients used local and systemic antimicrobials, and the
      sutures were removed at 7 days. RESULTS: Evaluations were carried out at 30 days,
      and 3 and 6 months, and all sites healed uneventfully. Neither infection nor
      significant pain was reported by the patients, and the material was covered by
      tissue at about 21 days. Mean horizontal gain of 1.72 +/- 0.59 mm (58.5%) at 6
      months and mean shrinkage of 1.22 +/- 0.46 mm (41.4%) were observed. There was a
      mean improvement in vertical gain of only 0.61 +/- 0. 77 mm, although 66. 7% of
      the treated sites showed a 1 to 2 mm gain. Clinically, the total gain in the
      subjects was very effective and matched the receptor tissues nicely. CONCLUSIONS:
      ADM may be a suitable material for the treatment of soft tissue ridge deformities
      due to its biocompatibility, color matching, and horizontal gain. Additional
      controlled, comparative trials are necessary to establish its advantages and
      potential compared to autogenous soft tissue techniques.

PMID- 11288803
TI  - A review of the medical treatment of primary aldosteronism.
AB  - PURPOSE: Use of the aldosterone-to-renin ratio (ARR) has suggested that at least
      one in 10 hypertensive subjects have primary aldosteronism (PA). There is thus a
      timely need to review the literature for effective drug therapies and to
      speculate on other therapeutic options by taking into account recent advances in
      understanding of the PA disease pathophysiological process. DATA SOURCE: A
      MEDLINE and EMBASE search of all articles published from the start of the
      databases until July 1999 and reviews of the bibliographies of textbooks. STUDY
      SELECTION: Primary research articles on the medical treatment of PA with emphasis
      on diagnosis, treatment option, drug dosage, therapeutic response and adverse
      drug effect. DATA EXTRACTION: Study design and quality were assessed. Relevant
      data on diagnostic methodology, drug usage and response were analysed and
      compared. DATA SYNTHESIS: A select number of subjects with aldosterone-producing
      adenoma (APA) can be expected to respond well to surgical treatment For the
      majority of PA cases especially subjects with idiopathic hyperaldosteronism
      (IHA), long-term medical treatment is now safe and feasible although no
      randomized controlled trials have been carried out to date. The best therapeutic
      response is obtained by directly antagonizing aldosterone at the receptor level
      using medium to low dose spironolactone and this response can be predicted by a
      raised ARR. The response to other potassium-sparing diuretics and calcium channel
      blockers are modest. IHA responds better than angiotensin II-unresponsive APA to
      angiotensin converting enzyme inhibitors and this may also be true with
      angiotensin II receptor blockers. The discovery of the aldosterone synthase gene
      opens up the possibility for gene therapy. CONCLUSION: The diagnosis of PA allows
      appropriate management with resultant blood pressure control in many hypertensive
      subjects who otherwise have resistant hypertension despite multiple drug therapy.

PMID- 11288804
TI  - Primary aldosteronism: revival of a syndrome.

PMID- 11288805
TI  - Gender and the relationship between resting heart rate and left ventricular
      geometry.
AB  - OBJECTIVES: Heightened mortality is common to both an elevated resting heart rate
      and left ventricular hypertrophy (LVH). We examined the relationship between
      resting heart rate and left ventricular geometry. METHODS: We analysed resting
      heart rate and echocardiographic data on 1,685 individuals aged 25-93 years, 756
      males and 929 females, without heart failure. The study population, 719
      normotensives and 966 untreated hypertensives, was derived from the Egyptian
      National Hypertension Project (1991-94); a cross-sectional study of the
      prevalence of hypertension and cardiovascular risk factors in Egyptians. The mean
      of the last two of three heart rate readings was used to represent the resting
      heart rate. RESULTS: Left ventricular mass index (LVMI) was weakly inversely
      related to heart rate in total males (r= -0.14, P< 0.0005) and total females (r= 
      0.1, P= 0.007) after controlling for age and blood pressure. The relative wall
      thickness (RWT) of the left ventricle was positively associated with heart rate
      in females. Resting heart rate increased linearly from 83.8 to 89 b.p.m. (P=
      0.03) from the lowest (< or = 0.33) to highest (> or = 0.47) RWT quintiles in
      hypertensive females after adjusting for age and blood pressure. In both those
      with and without LVH (defined as LVMI > 125 g/m2), hypertensive females with RWT
      > 0.45 compared to those with RWT < or = 0.45 had consistently higher resting
      heart rate (93.8 b.p.m. versus 84.2 b.p.m., P = 0.047 and 88.9 b.p.m. versus 85
      b.p.m., P = 0.005, respectively) after adjusting for age and blood pressure. No
      such relationship was found in males. CONCLUSIONS: Among hypertensive females, an
      elevated resting heart rate is associated with abnormal left ventricular
      geometry, namely, concentric left ventricular remodelling and hypertrophy.

PMID- 11288806
TI  - Cardiovascular risk stratification in hypertensive patients: impact of
      echocardiography and carotid ultrasonography.
AB  - BACKGROUND: Decision about the management of hypertensive patients should not be
      based on the level of blood pressure alone, but also on the presence of other
      risk factors, target organ damage (TOD) and cardiovascular and renal disease.
      OBJECTIVE: To evaluate the impact of echocardiography and carotid ultrasonography
      in a more precise stratification of absolute cardiovascular risk. METHODS: Never
      treated essential hypertensives (n = 141; 73 men, 68 women, mean age 46 +/- 11
      years) referred for the first time to our out-patient clinic were included in the
      study. They underwent the following procedures: (1) family and personal medical
      history, (2) clinical blood pressure (BP) measurement, (3) routine blood
      chemistry and urine analysis, (4) electrocardiogram, (5) echocardiogram, (6)
      carotid ultrasonogram. Risk was stratified according to the criteria suggested by
      the 1999 WHO/ISH guidelines. TOD was initially evaluated by routine procedures
      only, and subsequently reassessed by using data on cardiac and vascular structure
      obtained by ultrasound examinations (left ventricular hypertrophy (LVH) as left
      ventricular mass index (LVMI) > 134 g/m2 in men and > 110 g/m2 in women; carotid
      plaque as focal thickening > 1.3 mm). RESULTS: According to the first
      classification 20% were low-risk patients, 50% medium-risk, 22% high-risk and 8%
      very-high-risk patients. A marked change in risk stratification was obtained when
      TOD was assessed by adding ultrasound examinations: low-risk patients 18%, medium
      risk 28%, high-risk 45%, very-high-risk patients 9%. CONCLUSIONS: The detection
      of TOD by ultrasound techniques allowed a much more accurate identification of
      high-risk patients, who represented a very large fraction (45%) of the patient
      population seen at our hypertension clinic. In particular, a large proportion of
      patients classified as at moderate risk by routine investigations were instead
      found to be at high risk when ultrasound examinations were added. The results of
      this study suggest that cardiovascular risk stratification only based on simple
      routine work-up can often underestimate overall risk, thus leading to a
      potentially inadequate therapeutic management especially of low-medium risk
      patients.

PMID- 11288807
TI  - Arterial stiffness and cardiovascular risk factors in a population-based study.
AB  - OBJECTIVE: To determine the relationships between pulse wave velocity (PWV), an
      estimate of arterial distensibility and cardiovascular risk factors. DESIGN: This
      cross-sectional population-based study was carried out from 1995 to 1997 to
      investigate these relationships. POPULATION AND METHODS: Some 993 subjects, aged
      35-64 years (52.7% men), living in the south-west of France, were randomly
      selected from electoral rolls and participated in a cross-sectional study.
      Medical examinations were performed by specially trained medical staff. Carotid
      femoral PWV was measured using a semiautomatic device (Complior, Garges les
      Gonesse, France). The relationships between PWV and risk factors were assessed,
      first in subjects not treated with hypolipidaemic, antidiabetic and
      antihypertensive drugs and then in treated subjects. In subjects not treated for
      cardiovascular risk factors, age, gender, systolic blood pressure (SBP) and heart
      rate (P< 0.001) were the variables significantly associated with PWV. In treated
      patients, age (P < 0.01), SBP (P < 0.001), heart rate (P < 0.001), apolipoprotein
      B (P< 0.05) and the number of treated cardiovascular risk factors (P< 0.05) were
      positively correlated with PWV. CONCLUSION: This study shows that, in a sample of
      subjects at high risk, the cumulative influence of risk factors, even treated, is
      an independent determinant of arterial stiffness. These results suggest that PWV
      may be used as a relevant tool to assess the influence of cardiovascular risk
      factors on aortic stiffness in high-risk patients.

PMID- 11288808
TI  - Relationships of heart rate and heart rate variability with conventional and
      ambulatory blood pressure in the population.
AB  - BACKGROUND: Most studies on relationships between blood pressure and autonomic
      nervous function, assessed by power spectral analysis of heart rate variability,
      have used conventional or clinic blood pressure measurements in selected
      subjects, which may have influenced the results. OBJECTIVE: We aimed to
      investigate, in a population-based approach, associations of heart rate and heart
      rate variability, assessed in basal resting conditions and in response to
      standing, with conventional blood pressure measured by an investigator, and with
      ambulatory blood pressure monitored outside the laboratory. METHODS: RR interval
      and respiration were registered in 614 men and women, ages 25-89 years. After
      exclusion of subjects with myocardial infarction or diabetes and elimination of
      unsatisfactory recordings, 549 subjects remained for analyses at supine rest and
      515 of these to assess the orthostatic responses. Hypertension was present in 39%
      of the subjects. The low-frequency (LF) and high-frequency (HF) components of
      heart rate variability were quantified by use of autoregressive modelling and
      expressed in absolute and normalized units. RESULTS: At supine rest, indices of
      heart rate variability were not independently related to 24 h systolic blood
      pressure, whereas some indices showed weak associations with diastolic 24 h
      pressure; the relationships were in general stronger for conventional blood
      pressure. For example, partial correlation coefficients of the relationships of
      the LF: HF ratio with systolic pressure were 0.12 (P < or = 0.01) for
      conventional pressure and 0.02 (NS) for 24 h pressure; these coefficients
      amounted to 0.20 (P < or = 0.001) and 0.11 (P < or = 0.01) for the diastolic
      pressures. The decrease of HF power and the increase of the LF:HF ratio on
      standing were significantly blunted at higher blood pressure, both when measured
      conventionally and by ambulatory monitoring (P < or = 0.001 for the LF: HF
      ratio). CONCLUSIONS: Relationships between autonomic nervous function at rest,
      assessed by use of power spectral analysis of heart rate variability, and
      conventional blood pressure, can at least partly be ascribed to the influence of
      the measurement conditions, whereas the orthostatic autonomic responses appear to
      be influenced by blood pressure per se.

PMID- 11288809
TI  - Relationship of the Trp64Arg polymorphism of the beta3-adrenoceptor gene to
      central adiposity and high blood pressure: interaction with age. Cross-sectional
      and longitudinal findings of the Olivetti Prospective Heart Study.
AB  - METHODS: The association of the Trp64Arg polymorphism of the beta3-adrenoceptor
      (beta3-AR) gene with high blood pressure, central adiposity and other features of
      the metabolic syndrome was investigated in a large unselected sample of a white
      male working population in Southern Italy (n = 979). RESULTS: In the whole
      population, subjects heterozygous for the Trp64Arg mutation (11.2%) were not
      different from the homozygous Trp64Trp for any of the variables investigated.
      However, upon stratification for age, among men in the upper tertile of age (> 53
      years), the Trp64Arg genotype was associated with higher waist: hip ratio (0.992
      +/- 0.021 versus 0.982 +/- 0.037, P< 0.05), serum uric acid (6.34 +/- 1.50 versus
      5.75 +/- 1.30 micromol/l, P < 0.05) and systolic blood pressure (144.3 +/- 19.4
      versus 136.9 +/- 18.9 mmHg, P< 0.05) compared with the wild-type homozygotes.
      Accordingly, in the same age group, the carriers of Trp64Arg genotype were more
      often in the upper tertile of abdominal adiposity (69.7 versus 43.7%, P< 0.02)
      and serum uric acid (56.3 versus 34.8%, P < 0.02) and were more often
      hypertensive (68.6 versus 57.6%, P< 0.058) than the Trp64Trp homozygotes. No such
      differences were observed in younger age groups. No association was found with
      fasting serum insulin and the homeostasis model assessment (HOMA) index of
      insulin resistance. Furthermore, in a subgroup of 457 men for whom retrospective
      20-year follow-up data were available, the variant genotype was associated with a
      higher probability of developing overweight (44.7 versus 27.0%, P < 0.05) and a
      trend to higher blood pressure (52.6 versus 38.4%, P = 0.09) over 20 years.
      CONCLUSION: We conclude that the Trp64Arg variant of the beta3-AR receptor
      predicts a greater tendency to develop abdominal adiposity and high blood
      pressure with advancing age.

PMID- 11288810
TI  - Angiotensin II type 1 receptor-153A/G and 1166A/C gene polymorphisms and increase
      in aortic stiffness with age in hypertensive subjects.
AB  - OBJECTIVES: Arterial stiffness is associated with excess morbidity and mortality,
      independently of other cardiovascular risk factors. Age is the main determinant
      responsible for arterial wall changes leading to arterial stiffening.
      Environmental and genetic factors may however influence the magnitude of the
      effects of age on large artery stiffness. DESIGN AND METHODS: The present study
      assessed whether or not the relationship between age and aortic stiffness was
      influenced by genetic variants of angiotensinogen (AGT 174T/M, 235M/T),
      angiotensin converting enzyme (ACE I/D), angiotensin II type 1 receptor (AT1
      1166A/C, -153A/G) and aldosterone synthase (CYP11B2 -344T/C). This study was
      realized in 441 untreated hypertensive subjects of European origin (aged 18-74
      years). Aortic stiffness was assessed by carotid-femoral pulse wave velocity
      (PWV). RESULTS: Carriers of the angiotensin II type 1 receptor -153G allele
      showed a steeper age/PWV relationship than the AT1 -153AA subjects. The effect of
      the AT1 -153A/G polymorphism on aortic stiffness became apparent after the age of
      55 years. In subjects with the AT1 1166C allele, the relationship age/PWV is
      shifted upward, indicating higher values of aortic stiffness at any age compared
      to the AT1 1166AA patients. Carriers of both the AT1 1166C and -153G alleles
      presented the additive effects of these 2 genotypes on aortic stiffness.
      Angiotensinogen, ACE and CYP11B2 genotypes did not influence the effects of age
      on PWV. CONCLUSIONS: AT1 receptor genotypes could influence arterial ageing in
      hypertensive subjects. These results also show that the association between
      genotypes and arterial stiffness may manifest itself later in life.

PMID- 11288811
TI  - Correlation of endothelial function in large and small arteries in human
      essential hypertension.
AB  - OBJECTIVES: The structure and function of blood vessels varies along the vascular
      tree, and alterations found in hypertension are also different. The aim of this
      study was to determine whether non-invasive measurement of endothelial function
      in conduit arteries reflects that of subcutaneous resistance arteries measured in
      vitro. METHODS AND RESULTS: Sixteen essential hypertensive patients (aged 50 +/-
      2 years) were studied. Flow-mediated dilation (FMD) during reactive hyperemia
      (endothelium-dependent) and sublingual nitroglycerin (NTG)-induced dilatation
      (endothelium-independent) were assessed in brachial arteries by ultrasound.
      Structure, and acetylcholine (10(-9) to 10(-4) mol/l) and sodium nitroprusside
      (SNP, 10(-8) to 10(-3) mol/l)-induced vasorelaxation of resistance arteries
      dissected from gluteal subcutaneous biopsies were measured in vitro using a
      pressurized myograph. Brachial artery FMD and NTG-induced dilatation were 8.4 +/-
      1.0 and 18.1 +/- 1.4%, respectively. Resistance arteries of hypertensive patients
      showed greater media:lumen ratio (8.6 +/- 0.4 versus 5.9 +/- 0.3% in normotensive
      subjects, P< 0.01), and maximal acetylcholine responses was diminished to 75 +/-
      6% compared to normotensive subjects (97 +/- 2%, P< 0.01). FMD correlated with
      maximal acetylcholine responses (r2 = 0.57, P< 0.001). FMD did not correlate
      significantly with the media: lumen ratio of resistance arteries (r2 = -0.22, P=
      0.07). By multivariate analysis, FMD predicted resistance artery endothelial
      function independently of age, sex, body mass index, blood lipid status and lumen
      diameter of brachial artery (beta = 0.81, P< 0.001). CONCLUSIONS: Endothelial
      dilatory responses are similar in large and small arteries in hypertensive
      patients. Abnormal FMD in the brachial artery predicts the presence of
      endothelial dysfunction in human resistance arteries, suggesting that impairment
      of endothelial function is a generalized alteration in hypertension. Ultrasound
      measurement of endothelial dysfunction in the brachial artery appears to be less
      sensitive than in-vitro measurement in resistance arteries.

PMID- 11288812
TI  - L-Arginine improves endothelial function in renal artery of hypertensive Dahl
      rats.
AB  - OBJECTIVES: To clarify whether endothelium-derived contracting factor (EDCF) is
      developed in renal artery of hypertensive Dahl rats and whether prolonged oral L
      arginine treatments prevent development of EDCF and hypertension. DESIGN: The
      effect of prolonged salt treatment with or without L-arginine on the renal artery
      was examined. METHODS AND RESULTS: Dahl salt-sensitive and -resistant rats were
      fed a 0.4 or an 8% NaCl diet for 4 weeks. High sodium intake increased arterial
      pressure in Dahl salt-sensitive rats. The rings of renal arteries were suspended
      for isometric tension recording. Only in the hypertensive rats, more than 1
      micromol/l acetylcholine induced an endothelium-dependent contraction response.
      The contraction was completely inhibited by indomethacin or ONO-3708
      [prostaglandin H2 (PGH2)/thromboxane A2 (TXA2) receptor antagonist], and
      partially inhibited by OKY-046 (TXA2 synthetase inhibitor). Acetylcholine-induced
      relaxation was significantly depressed in hypertensive rats, which was partially
      improved by SQ29548 (PGH2/TXA2 receptor antagonist). Oral L-arginine, but not ONO
      8809 (orally active PGH2/TXA2 receptor antagonist) treatment, inhibited the
      contraction and amended the relaxation. The endothelium-independent contraction
      to TXA2 receptor agonist U46619 and relaxation to nitroprusside were not altered
      by L-arginine treatment The L-Arginine treatment reduced blood pressure and
      sodium retention with increases in urinary NO2-/NO3- and cGMP excretion.
      Hydralazine treatment also inhibited development of EDCF. CONCLUSIONS: The
      present results suggest that impaired endothelium-dependent relaxation to
      acetylcholine is caused in part by induction of EDCF synthesis/release in renal
      arteries of hypertensive Dahl rats. L-arginine can attenuate sodium retention and
      development of hypertension, which lead to a decrease in EDCF synthesis in renal
      arteries.

PMID- 11288813
TI  - Effect of an ET(B)-selective and a mixed ET(A/B) endothelin receptor antagonist
      on venomotor tone in deoxycorticosterone-salt hypertension.
AB  - OBJECTIVES: Because the ET(B) receptor is important in venoconstriction, we
      examined the effects of a selective ET(B) receptor antagonist (A-1 92621) and a
      mixed ET(A/B) receptor antagonist (A-182086) on endogenous endothelin-1 (ET-1)
      contributions to elevated venomotor tone in deoxycorticosterone acetate-salt
      (DOCA-salt) hypertension. METHODS: Changes in venomotor tone were assessed using
      repeated measurements of mean circulatory filling pressure (MCFP) in awake,
      uninephrectomized, DOCA-salt-treated rats and uninephrectomized sham rats
      following intravenous (i.v.) injections of the ET(B) antagonist (12 mg/kg i.v.)
      or the ET(A/B) antagonist (12 mg/kg i.v.) alone, or 1 h before ganglion blockade
      with hexamethonium (30 mg/kg i.v.). RESULTS: DOCA-salt rats were hypertensive and
      exhibited higher MCFP than sham normotensive rats. The ET(A/B) receptor
      antagonist lowered mean arterial blood pressure (MABP) in DOCA-salt and sham
      rats, but MCFP fell in DOCA-salt rats only. The ET(B) antagonist produced no
      changes in MCFP while MABP increased in both groups. Pre-treatment of DOCA-salt
      rats, but not sham rats, with either antagonist produced greater declines in MCFP
      following hexamethonium than after hexamethonium alone. CONCLUSIONS: The present
      study confirms previous findings of elevated MCFP in DOCA-salt hypertensive rats
      compared to normotensive rats, but is the first to show that venomotor tone is
      affected by the actions of endogenous ET-1 acting at ET(B) receptors to modulate
      sympathetic input to the veins, as well as direct actions of ET-1 on vascular
      smooth muscle (VSM) ET(A) receptors. We also showed that mixed ET(A/B) receptor
      antagonism was effective in lowering MCFP and MABP in DOCA-salt hypertensive
      rats.

PMID- 11288814
TI  - Role of c-Src in the regulation of vascular contraction and Ca2+ signaling by
      angiotensin II in human vascular smooth muscle cells.
AB  - OBJECTIVE: Tyrosine kinases, typically associated with growth-signaling pathways,
      also play a role in Ang II-stimulated vascular contraction. However the specific
      kinases involved are unclear. We hypothesize here that c-Src, a non-receptor
      tyrosine kinase, is an important upstream regulator of vascular smooth muscle
      cell (VSMC) Ca2+ signaling and associated vascular contraction induced by Ang II.
      METHODS: Cultured VSMCs from resistance arteries of healthy subjects were
      studied. Human VSMCs electroporated with anti-c-Src antibody and c-Src-deficient
      VSMCs from small arteries of c-Src knockout mice (Src-/-mVSMCs) were also
      investigated. Intracellular free Ca2+ concentration ([Ca2+]i), c-Src activity and
      IP3 production were measured by fura 2, immunoblot and radioimmunoassay
      respectively. Contraction was examined in intact rat small arteries. RESULTS: Ang
      II rapidly increased VSMC c-Src activity, with peak responses obtained at 1 min.
      Ang II induced a biphasic [Ca2+]i response (Emax = 636 +/- 123 nmol/l). The
      initial [Ca2+]i transient, mediated primarily by Ca2+mobilization, was dose
      dependently attenuated by the selective Src inhibitor, PP2, but not by PP3
      (inactive analogue). Ang II-elicited [Ca2+]i responses were blunted in cells
      electroporated with anti-c-Src antibodies and in c-Src-/-mVSMCs. Src inhibition
      decreased Ang II-induced generation of IP3 in human VSMCs. Ang II dose
      dependently increased vascular contraction (Emax = 40 +/- 6.5%). These responses
      were attenuated by PP2 (Emax = 7.8 +/- 0.08%) but not by PP3 (Emax = 35 +/-
      4.5%). CONCLUSIONS: Our findings identify c-Src as an important regulator of VSMC
      [Ca2+]i signaling and implicate a novel contractile role for this non-receptor
      tyrosine kinase in Ang II-stimulated vascular smooth muscle.

PMID- 11288815
TI  - A calcium channel blocker, benidipine, inhibits intimal thickening in the carotid
      artery of mice by increasing nitric oxide production.
AB  - OBJECTIVE: Recent studies suggest that several calcium channel blockers exert
      their protective effects against vascular disorders by increasing nitric oxide
      (NO) production from the endothelium. The purpose of this study was to clarify
      the effects of a long-lasting calcium channel blocker, benidipine, on vascular
      remodeling. METHODS: The left common carotid arteries of mice were completely
      ligated just proximal to the carotid bifurcation. Treatment with benidipine (3
      mg/kg per day) or vehicle was started 1 week before the carotid ligation, and
      continued throughout the experiments. Four weeks after the carotid ligation,
      these mice were killed and vascular remodeling was analyzed. Moreover, NO
      production and endothelial NO synthase (eNOS) expression were assessed. RESULTS:
      At 4 weeks after ligation, the neointimal area in the vehicle-treated mice was
      39,400 +/- 4,900 microm2 (n = 8), whereas that in the drug-treated mice was
      reduced to 18,300 +/- 3,800 microm2 (n = 10). Consequently, the luminal area was
      35% larger in the drug-treated mice. Benidipine increased the basal as well as
      agonist-induced NO production from the endothelium, detected by Griess method or
      NOx analyzer. Endothelial NOS expression in vessels of the drug-treated mice was
      increased compared with that of the vehicle-treated mice. CONCLUSION: Our data
      provide evidence that benidipine increases NO production via increment of eNOS
      protein in vessels and prevents intimal thickening in mice. These results show
      the possibility of benidipine as a protective tool against vascular remodeling
      independent of its effect on blood pressure.

PMID- 11288816
TI  - Association of high resting end tidal CO2 with carotid artery thickness in women,
      but not men.
AB  - BACKGROUND: A previous study found high resting end tidal CO2 (PetCO2) to be an
      independent determinant of systolic blood pressure in women, but not men. The
      present study investigates the association of PetCO2 with the common carotid
      artery intima-media thickness (IMT) and wall-to-lumen (W/L) ratio in a sample of
      normotensive men and women. DESIGN AND METHODS: Resting PetCO2 of 188 healthy
      volunteers, including 88 men and 100 women, in the Baltimore Longitudinal Study
      on Aging was monitored continuously for 25 min via a respiratory gas monitor. At
      another session, carotid artery IMT was determined via high-resolution B-mode
      carotid ultrasonography. The ratio of IMT to carotid artery diameter was
      calculated as W/L ratio. Resting blood pressure was determined oscillometrically
      every 5 min for 20 min during each session. RESULTS: Univariate associations of
      PetCO2 with systolic blood pressure (SBP) (P< 001), IMT (P< 001) and W/L ratio
      (P< 001) were significant in women, but not men. Multiple regression analyses
      showed that high resting PetCO2 was a predictor of SBP (P < 01), IMT (P< 01) and
      W/L ratio (P< 01) in women, independent of age, body mass index and SBP. For men,
      age (P < 001) and SBP (P < 01) were independent predictors of carotid IMT, while
      age (P< 001) was the only independent predictor of W/L ratio in men. CONCLUSIONS:
      This study indicates that PetCO2 can play a role in cardiovascular structure, as
      well as function, in women, and that the relationship is independent of the
      association of PetCO2 with blood pressure.

PMID- 11288817
TI  - Inhibition of angiotensin II-induced facilitation of sympathetic
      neurotransmission in the pithed rat: a comparison between losartan, irbesartan,
      telmisartan, and captopril.
AB  - OBJECTIVE: Numerous studies have shown that angiotensin II enhances sympathetic
      nervous transmission. The objective of the present study was to quantify the
      inhibitory effect of the angiotensin II type 1 (AT1) receptor blockers losartan,
      irbesartan and telmisartan and the angiotensin converting enzyme (ACE) inhibitor
      captopril on sympathetic neurotransmission and to compare the potency of these
      agents both at the presynaptic and the postsynaptic levels. DESIGN: In the male,
      normotensive pithed rat model, we studied the effect of losartan (1, 3, 10 and 30
      mg/kg), irbesartan (3, 10, 30 and 60 mg/kg), telmisartan (0.3, 1, 3 and 10 mg/kg)
      and captopril (1.5, 5, 15 and 45 mg/kg) on electrical stimulation of the thoraco
      lumbar spinal cord. To investigate the interaction between postsynaptic AT1
      receptors and alpha-adrenoceptors, the effects of these compounds on pressor
      responses to exogenous noradrenaline were studied. RESULTS: Stimulation of the
      thoracolumbar spinal cord caused a stimulation-frequency dependent rise in
      diastolic blood pressure (DBP) that could be dose-dependently reduced by both AT1
      receptor blockade and ACE inhibition. Interestingly, the highest doses of the AT1
      antagonists caused less than maximal reduction in the rise in DBP. This
      phenomenon was not observed after ACE inhibition by captopril. In experiments
      with exogenous noradrenaline, no effect of AT1 blockade or ACE inhibition on
      alpha-adrenoceptor-mediated blood pressure responses was seen. CONCLUSION: We
      conclude that, in the pithed rat model, the effects of stimulation of the thoraco
      lumbar spinal cord on DBP are counteracted by blockade of presynaptically located
      AT1 receptors. The order of potency concerning sympatico-inhibition is
      telmisartan > losartan > irbesartan. Regarding the inhibition of angiotensin II
      induced facilitation of sympathetic neurotransmission, marked differences were
      observed between selective AT1 blockade and ACE inhibition. The finding that all
      three AT1 blockers cause less than maximal inhibition in their highest doses, as
      opposed to captopril, suggests that this is a class effect of the AT1
      antagonists.

PMID- 11288818
TI  - Monoclonal antibody against brain natriuretic peptide and characterization of
      brain natriuretic peptide-transgenic mice.
AB  - OBJECTIVE: Brain natriuretic peptide (BNP) is a ventricular hormone with
      natriuretic, diuretic and vasodilatory actions. Acute infusion of BNP reduces
      cardiac pre- and after-load in healthy and diseased subjects, but its long-term
      therapeutic usefulness remains unclear. DESIGN: We prepared a monoclonal antibody
      specific to mouse BNP, and characterized transgenic mice overexpressing BNP in
      the liver (BNP-Tg mice) as a model of its chronic overproduction. METHODS:
      Radioimmunoassay and neutralization experiments using the monoclonal antibody, KY
      mBNP-I, were performed in BNP-Tg mice in conjunction with examinations of blood
      pressure (BP) and other markers for body fluid homeostasis. RESULTS: We developed
      highly sensitive radioimmunoassay to mouse BNP. In BNP-Tg mice, the plasma BNP
      concentration increased more than 100-fold, while ventricular BNP concentration
      did not alter, suggesting that ventricular BNP production was not down-regulated
      in BNP-Tg mice. The BNP concentration in the kidneys was 10-fold higher than
      nontransgenic (nonTg) littermates, accompanied with marked reduction in the
      atrial natriuretic peptide (ANP) concentration, that may be due to binding of
      circulating BNP to the natriuretic peptide receptors. BNP-Tg mice showed
      significantly low arterial BP, and a bolus intraperitoneal administration of
      KYmBNP-I completely abolished enhanced cGMP excretion in the urine and
      significantly increased the systolic BP. CONCLUSION: These results suggested that
      biological actions of BNP last and reduce cardiac overload in its longterm
      overproduction in the transgenic mouse model.

PMID- 11288819
TI  - Abnormal thiol reactivity of tropomyosin in essential hypertension and its
      association with abnormal sodium-lithium countertransport kinetics.
AB  - OBJECTIVES: To identify a thiol protein that is abnormal in a subgroup of
      essential hypertensive (EHT) patients who have a strong family history of
      hypertension and cardiovascular disease and have a low Km of erythrocyte Na/Li
      countertransport (CT). METHODS: To detect biotin maleimide labelling of a key
      thiol protein to investigate its reaction with N-ethylmaleimide (NEM) in normal
      and EHT erythrocytes. RESULTS: The thiol protein of 33 kDa apparent molecular
      weight (p33) identified by the loss of labelling with biotin maleimide was
      identified as tropomyosin due to its retarded running in 6 mol/l urea gels and
      immunoblotting. The NEM reaction with p33 detected by loss of subsequent biotin
      maleimide labelling is biphasic in normal control erythrocytes with the rate in
      the first 30 s double that after 30 s. In EHT erythrocytes NEM reaction (1) after
      30 s is faster than normal and (2) in the first 30 s causes a paradoxical
      increase in apparent biotin maleimide labelling. In normal control erythrocytes,
      the loss of biotin maleimide labelling with NEM reaction or the faster
      phenylmaleimide reaction follows the same time course as the decrease in Km of
      Na/Li CT. CONCLUSIONS: NEM reaction with p33 requires two thiols. Only the
      cytoskeletal form of tropomyosin from the TM3 gene has more than one thiol group
      and agrees with SDS-PAGE mobility. Tropomyosin is a strong candidate to explain
      the familial abnormality in EHT with abnormal Na/ Li CT and it could explain many
      of the characteristics of this disease.

PMID- 11288820
TI  - Dipyridamole-atropine stress echocardiography versus exercise SPECT scintigraphy
      for detection of coronary artery disease in hypertensives with positive exercise
      test.
AB  - OBJECTIVES: Many different stress echocardiographic and radionuclide perfusion
      imaging tests have been proposed for detecting epicardial coronary artery disease
      (CAD) in hypertensive patients. Their relative diagnostic and prognostic value
      has not been exactly established. BACKGROUND: A positive exercise
      electrocardiography test has a low diagnostic specificity in hypertensive
      patients and warrants for a complementary imaging test to confirm the diagnosis
      of coronary artery disease. METHODS: Hypertensive patients (n = 53), (29 males,
      aged 58 +/- 10 years) with normal left ventricular function detected by
      echocardiography and previous positive exercise test ( > or = 0.15 mV of ST
      segment depression on 12 lead electrocardiogram) underwent dipyridamole-atropine
      stress echocardiography (DASE) and thallium-201 stress/ rest myocardial single
      photon emission computed tomography (SPECT). All patients had coronary
      angiography within 15 days and independently of imaging test results. RESULTS:
      Coronary angiogram showed significant ( > or = 50% qualitatively assessed
      diameter reduction) epicardial coronary artery disease in 23 (43%) patients.
      Sensitivity for detection of coronary artery disease was significantly higher for
      scintigraphy (DASE = 78% versus SPECT = 100%, P < 0.05) while specificity was
      higher for echo (DASE = 100% versus SPECT = 47%, P < 0.00001). Diagnostic
      accuracy was also higher for echo (DASE = 91% versus SPECT = 70%, P < 0.01).
      CONCLUSION: In patients with exercise-nduced ST segment depression, dipyridamole
      stress echo and SPECT perfusion scintigraphy are both good diagnostic options,
      with DASE characterized by higher specificity, lower sensitivity, and at least
      comparable diagnostic accuracy than SPECT.

PMID- 11288821
TI  - Effects of troglitazone and temocapril in spontaneously hypertensive rats with
      chronic renal failure.
AB  - OBJECTIVE: The insulin resistance state is common in humans and animals with
      chronic renal failure. We investigated the effects of troglitazone, an insulin
      sensitizer, on blood pressure and nephropathy in the remnant kidney model of
      spontaneously hypertensive rats (SHR). METHODS: Eight-week-old male SHR were
      subjected to five-sixth nephrectomy. At the age of 10 weeks, the rats were
      randomly allocated to groups that received troglitazone (70 mg/kg per day); the
      angiotensin converting enzyme inhibitor temocapril (10 mg/kg per day);
      troglitazone (70 mg/kg per day) plus temocapril (10 mg/kg per day), or a vehicle
      alone as an untreated control group. Systolic blood pressure (SBP) and urinary
      protein excretion were measured every 2 weeks. At the age of 22 weeks,
      biochemical measurements and histological examination were performed. RESULTS:
      Blood glucose, glycosylated hemoglobin and body weight were similar in the four
      groups. SBP, serum creatinine and glomerular sclerosis index were significantly
      reduced in all treated groups compared with those in the control group. Urinary
      protein excretion, glomerular volume and aortic media thickness were
      significantly decreased in temocapril-treated rats and troglitazone plus
      temocapril-treated rats compared with those in control rats. Although
      antihypertensive effects of troglitazone were minute compared with those of
      temocapril or troglitazone plus temocapril, there was no significant difference
      between the glomerular sclerosis indices in these three drug-treated groups.
      CONCLUSIONS: The results suggest that troglitazone has renoprotective effects in
      this rat model. These effects might be due to the inhibition of growth factors
      rather than to the minute hypotensive effect, although the mechanism remains to
      be elucidated.

PMID- 11288822
TI  - Follow-up of renal function in treated and untreated older patients with isolated
      systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial
      Investigators.
AB  - BACKGROUND: In the outcome trials that provided information on renal function in
      older hypertensive patients, diuretics and beta-blockers were mostly used as
      first-line drugs. The long-term renal effects of calcium-channel blockers remain
      unclear. OBJECTIVE: To compare the changes in renal function in 2,258 treated and
      2,148 untreated patients with isolated systolic hypertension, of whom 455 had
      diabetes mellitus and 390 had proteinuria. METHODS: We performed a post-hoc
      analysis of the double-blind placebo-controlled Systolic Hypertension in Europe
      (Syst-Eur) Trial. Active treatment was initiated with nitrendipine (10-40 mg/day)
      with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5
      25 mg/day), or both, titrated or combined to reduce the sitting systolic blood
      pressure by at least 20 mmHg, to less than 150 mmHg. The main outcome measures
      were serum creatinine concentration and creatinine clearance calculated by the
      formula of Cockroft and Gault. RESULTS: Serum creatinine concentration at the
      time when participants were randomly allocated to study groups was less than
      176.8 micromol/l (2.0 mg/dl), averaging 88 micromol/l. At the time of the last
      serum creatinine measurement, the blood pressure difference (P< 0.001) between
      the two groups was 11.6/4.1 mmHg. In the intention-to-treat analysis (11,427
      patient-years), serum creatinine and the calculated creatinine clearance were not
      influenced by active treatment. However, in the patients assigned randomly to
      receive active treatment, the incidence of mild renal dysfunction (serum
      creatinine at least 176.8 mmol/l) decreased by 64% (P= 0.04) and that of
      proteinuria by 33% (P= 0.03). Active treatment reduced the risk of proteinuria
      more in diabetic than in non-diabetic patients: by 71%, compared with 20% (P=
      0.04). In non-proteinuric patients, active treatment did not influence serum
      creatinine, whereas in patients with proteinuria at entry to the study, serum
      creatinine decreased on active treatment (P< 0.001). Furthermore, in on
      randomized treatment comparison stratified for risk at baseline, serum creatinine
      concentration did not change (P= 0.98) in patients continuing to receive
      monotherapy with nitrendipine, whereas it increased by 6.73 mmol/l (P < 0.001) in
      patients who received hydrochlorothiazide alone or in combination with other
      study medication (P < 0.001 for difference in trends). CONCLUSIONS: In older
      patients with isolated systolic hypertension, antihypertensive treatment starting
      with the dihydropyridine calcium-channel blocker, nitrendipine, did not decrease
      blood pressure at the expense of renal function and prevented the development of
      proteinuria, especially in diabetic patients.

PMID- 11288823
TI  - Behavioral discrimination of water motions caused by moving objects.
AB  - We tested whether goldfish, Carassius auratus, discriminate hydrodynamic stimuli
      caused by moving objects. Blindfolded goldfish responded to a passing object with
      changes in inter-gill-movement intervals. To learn whether goldfish can
      discriminate water motions caused by different moving objects we habituated them
      to a certain object stimulus. If the stimulus was altered, e.g., by altering
      speed, direction of motion, or size or shape of the object, fish again showed a
      temporary suspension of breathing when the object passed by. If animals failed to
      respond to an altered stimulus, we paired this stimulus with a weak electric
      shock during training. Goldfish discriminated object motion direction. In
      addition, in two choice experiments goldfish discriminated water motions caused
      by objects which moved with different speeds (e.g., 5 cm s(-1) versus 6 cm s(
      1)), or by objects which differed in size (e.g., 1 cm x 1 cm versus 1.4 cm x 1.4
      cm cross section), or shape (e.g., a round versus a triangular object). If object
      size and/or shape was varied quasi-randomly such that the faster moving object
      not always caused the greatest water velocities, fish still discriminated object
      speed.

PMID- 11288825
TI  - Responses of a population of antennal olfactory receptor cells in the female moth
      Manduca sexta to plant-associated volatile organic compounds.
AB  - Extracellular electrophysiological recordings were made from individual type-A
      trichoid sensilla on the antenna of the female sphinx moth Manduca sexta. A
      single annulus of the antenna bears about 1,100 of these sensilla, and each is
      innervated by two olfactory receptor cells. We tested the responses of these
      receptor cells to a panel of 102 volatile compounds, as well as three plant
      derived odor mixtures, and could discern three different functional types of type
      A trichoid sensilla. One subset of receptor cells exhibited an apparently narrow
      molecular receptive range, responding strongly to only one or two terpenoid
      odorants. The second subset was activated exclusively by aromatics and responded
      strongly to two to seven odorants. The third subset had a broad molecular
      receptive range and responded strongly to odorants belonging to several chemical
      classes. We also found receptor cells that did not respond to any of the odorants
      tested but were spontaneously active. Certain odorants elicited excitatory
      responses in some sensilla but inhibitory responses in others, and some receptor
      cells were strongly excited by certain odorants but inhibited by others.
      Impregnation of groups of receptor cells in type-A trichoid sensilla with
      rhodamine-dextran demonstrated that their axons project mainly to the large
      female glomeruli of the antennal lobe.

PMID- 11288824
TI  - Integration of ascending and descending inputs in the auditory midbrain of
      anurans.
AB  - In anurans, the midbrain torus semicircularis is involved in auditory processing
      and audio-motor integration. In this study, we examined the influence of
      descending forebrain projections on the auditory response properties and hence
      the audiomotor transmission of mesencephalic interface neurons. In order to
      investigate response integration, we performed intracellular recordings from
      torus neurons in an isolated brain preparation of Discoglossus pictus and Bombina
      orientalis and stimulated the auditory nerve, striatum, and the dorsal thalamus
      electrically with single pulses. Stimulation of all three sites could evoke
      responses in torus neurons that were either excitatory, inhibitory, or a mixture
      of both, with durations of up to several hundred milliseconds. Further, striatum
      and thalamus were activated by pulse trains (10-20 Hz, 50 pulses) immediately
      before stimulating the auditory nerve with single pulses. Thus, responses of
      torus neurons to "auditory" input were facilitated or suppressed for up to 2 min
      by striatum stimulation or only suppressed by thalamus stimulation. Intracellular
      labeling of recorded neurons revealed that response modulation by descending
      input mostly occurred in laminar nucleus neurons. These results suggest that
      descending forebrain projections to mesencephalic audiomotor interface neurons
      may play an important role in modifying acoustically guided behavior in anurans.

PMID- 11288826
TI  - Male recognition mechanism for female responses implies a dilemma for their
      localisation in a phaneropterine bushcricket.
AB  - The phonotactic behaviour of the duetting bushcricket Poecilimon ornatus was
      investigated on a walking compensator when two females responded to the male's
      call. Whenever two female clicks from different directions were presented within
      the time window, males tracked an intermediate course even when the two clicks
      were separated by up to 60 ms and differed widely in intensity. Thus, any signal
      arriving within that interval contributes to the localization of the female
      response. The inability of male P. ornatus to selectively track one of two
      females is in contrast to previous results found in other bushcricket species
      which track the leading of two singing animals. We suggest that the intermediate
      walking is a consequence of the basic ensiferan neuronal processing of song
      recognition and localization. Choice experiments in the natural habitat show that
      earlier or later during the phonotactic path--the male tracks that female which
      is favoured by the unpredictable acoustic conditions in dense vegetation.

PMID- 11288827
TI  - Location of the reproductive timer in the male cricket Gryllus bimaculatus DeGeer
      as revealed by local cooling of the central nervous system.
AB  - The location of the reproductive timer for the post-copulatory, time-fixed,
      sexually refractory stage was investigated in the male cricket Gryllus
      bimaculatus. This stage was defined as the interval between spermatophore
      protrusion and recommencement of copulation or a calling song. To inactivate the
      central nervous system locally and reversibly, different body regions were cooled
      to 10 degrees C for 20-30 min after spermatophore protrusion. A behavioural test
      then measured the duration of the refractory stage after males recovered from
      cooling. Males with the head, thorax and anterior abdomen cooled did not show a
      lengthening of that stage. In contrast, males with the entire abdomen or even the
      posterior abdominal segments containing only the 6th and terminal (7th-11th)
      abdominal ganglia showed a lengthening of the refractory stage up to, but not
      exceeding, the cooling duration. When 20-min cooling was interposed twice after
      spermatophore protrusion, the refractory stage was lengthened by about 40 min,
      indicating that interposed cooling did not reset the timer. These results are in
      agreement with our previous hypothesis that the reproductive timer for the
      refractory stage in the male cricket is located in the posterior abdominal
      ganglia, possibly within the terminal abdominal ganglion.

PMID- 11288828
TI  - The phosphoinositide signaling cascade is involved in photoreception in the leech
      Hirudo medicinalis.
AB  - The effects of BAPTA, heparin, and neomycin on electrical light responses were
      studied in the photoreceptors of Hirudo medicinalis. Light activation produces a
      fast increase in intracellular Ca2+ concentration (Cai) as detected with the
      fluorescent Ca2+ indicator calcium green-5N. Chelating intracellular calcium by
      injections of 10 mmol(-1) BAPTA suppresses spontaneous quantum bumps, reduces
      light sensitivity by more than 2 log(10) units, and substantially increases the
      latent period of light responses. BAPTA strongly inhibits the plateau phase of
      responses to long steps of light. Injections of 45-100 mg ml(-1) of heparin act
      in a similar manner to BAPTA, affecting the latency of the light responses even
      more. De-N-sulfated heparin, an inactive analog, is almost ineffective at the
      same concentration compared with heparin. Heparin diminishes the light-induced
      Cai elevation significantly, whereas de-N-sulfated heparin does not.
      Intracellular injections of 50-100 mmol l(-1) of the aminoglycoside neomycin,
      which inhibits phospholipase-C-mediated inositol 1,4,5-trisphosphate formation,
      acts similar to BAPTA and heparin. Pressure injections of the hydrolysis
      resistant analog of inositol 1,4,5-trisphosphate, inositol 2,4,5-trisphosphate,
      strongly depolarize leech photoreceptors and mimic an effect of light adaptation.
      These results suggest a close similarity between phototransduction mechanisms in
      leech photoreceptors and existing models for visual transduction in other
      invertebrate microvillar photoreceptors.

PMID- 11288829
TI  - Distance discrimination during active electrolocation in the weakly electric fish
      Gnathonemus petersii.
AB  - Weakly electric fish use active electrolocation for orientation at night. They
      emit electric signals (electric organ discharges) which generate an electrical
      field around their body. By sensing field distortions, fish can detect objects
      and analyze their properties. It is unclear, however, how accurately they can
      determine the distance of unknown objects. Four Gnathonemus petersii were trained
      in two-alternative forced-choice procedures to discriminate between two objects
      differing in their distances to a gate. The fish learned to pass through the gate
      behind which the corresponding object was farther away. Distance discrimination
      thresholds for different types of objects were determined. Locomotor and
      electromotor activity during distance measurement were monitored. Our results
      revealed that all individuals quickly learned to measure object distance
      irrespective of size, shape or electrical conductivity of the object material.
      However, the distances of hollow, water-filled cubes and spheres were
      consistently misjudged in comparison with solid or more angular objects, being
      perceived as farther away than they really were. As training continued, fish
      learned to compensate for these 'electrosensory illusions' and erroneous choices
      disappeared with time. Distance discrimination thresholds depended on object size
      and overall object distance. During distance measurement, the fish produced a
      fast regular rhythm of EOD discharges. A mechanisms for distance determination
      during active electrolocation is proposed.

PMID- 11288830
TI  - Structure of the Fe-heme in the hemodimeric hemoglobin from Scapharca
      inaequivalvis and in the T721 mutant: an X-ray absorption spectroscopic study at
      low temperature.
AB  - The Fe site structure in the recombinant wild-type and T721 mutant of the
      cooperative homodimeric hemoglobin (HbI) of the mollusc Scapharca itnaequivalvis
      has been investigated by measuring the Fe K-edge X-ray absorption near edge
      structure (XANES) spectra of their oxy, deoxy and carbonmonoxy derivatives, and
      the cryogenic photoproducts of the carbonmonoxy derivatives at T = 12 K.
      According to our results, the Fe site geometry in T72I HbI-CO is quite similar to
      that of human carbonmonoxy hemoglobin (HbA-CO), while in native HbI-CO it seems
      intermediate between that of HbA-CO and sperm whale MbCO. The XANES spectra of
      oxy and deoxy derivatives are similar to the homologous spectra of human HbA,
      except for T72I HbI, for which the absorption edge is blue-shifted (about + 1 eV)
      towards the spectrum of the oxy form. XANES spectra of the cryogenic
      photoproducts of HbA-CO (HbA*), HbI-CO (HbI*) and mutant HbI-CO (T72I HbI*) were
      acquired under continuous illumination at 12 K. The Fe-heme structures of the
      three photoproducts are similar; however, while in the case of HbA* and HbI* the
      data indicate incomplete structural relaxation of the Fe-heme towards its deoxy
      like (T) form, the relaxation in T72I HbI* is almost completely towards the
      proposed "high affinity" Fe-heme structure of T72I HbI. This evidence suggests
      that minor tertiary restraints affect the Fe-heme dynamics of T72I HbI,
      corresponding to a reduction of the energy necessary for the T --> R structural
      transition, which can contribute to the observed dramatic enhancement in oxygen
      affinity of this hemoprotein, and the decreased cooperativity.

PMID- 11288831
TI  - Synthetic undecapeptide (NTX10-20) of noxiustoxin blocks completely the I(A)
      potassium currents of cerebellum granular cells.
AB  - Native noxiustoxin (NTX) and synthetic peptides corresponding to its primary
      sequence, from positions 1-9, 1-14, 1-20, 10-20, 21-39 and 30 39, were prepared
      and assayed on the K+ currents of cerebellum granular cells, using the patch
      clamp technique in the whole-cell configuration system. Native toxin has a
      reversible inhibitory effect (IC50 = 360 nM), whereas synthetic peptides NTXI-20
      and NTX1-9 had a half-effective dose IC50 of approximately 2 and 10 microM,
      respectively, which correlates with their biological effects in vivo. Synthetic
      peptide NTX10-20 was quite remarkable in having a preference for the IA current,
      which was completely inhibited at high peptide concentration. The effects of the
      other peptides (NTXI 14, NTX21-39 and NTX30-39), although positive and
      reversible, required higher concentrations (50 200 microM) to block both
      currents, suggesting no affinity or, at least, much lower specificity for the
      channels responsible for the potassium currents in the granular cells studied.

PMID- 11288832
TI  - NMR stray-field analysis of oil drop size distribtuion in peanut cotyledons.
AB  - The technique of stray-field NMR has been applied to the study of an oil-bearing
      seed. It is found to provide additional information about the smallest size of
      oil drops within the cotyledon not easily measurable by other methods. A peanut
      was chosen as a convenient seed to investigate so as to allow comparison with
      previously published NMR pulsed field gradient data. We find a broad distribution
      of oil drop sizes ranging from a lower limit of order 0.26 microm up to a maximum
      of approximately 1.3 microm.

PMID- 11288833
TI  - Electron paramagnetic resonance study of honeybee Apis mellifera abdomens.
AB  - Although ferromagnetic material has been detected in Apis mellfera abdomens and
      identified as suitable for magnetic reception, physical and magnetic properties
      of these particles are still lacking. Electron paramagnetic resonance is used to
      study different magnetic materials in these abdomens. At least four iron
      structures are identified: isolated Fe3+ ions, amorphous FeOOH, isolated
      magnetite nanoparticles of about 3 x 10(2) nm3 and 10(3) nm3 volumes, depending
      on the hydration degree of the sample, and aggregates of these particles. A low
      temperature transition (52-91 K) was observed and the temperature dependence of
      the magnetic anisotropy constant of those particles was determined. These results
      imply that biomineralized magnetites are distinct from inorganic particles and
      the parameters presented are relevant for the refinement of magnetoreception
      models in honeybees.

PMID- 11288834
TI  - Membrane potential and its electrode-recorded counterpart in an electrical model
      of an olfactory sensillum.
AB  - Insect receptor neurons are surrounded with auxiliary cells and encased in a
      hair. Their electrical activity is usually recorded with an electrode located at
      the tip of the hair. Analytical expressions giving the membrane potential along
      the sensory dendrite and the tip-recorded potential are derived for a neuron in
      steady-state conditions. They formally close the gap between theoretical models
      and experimental measurements, when transduction mechanisms and active membrane
      properties are not taken into account. It is shown that the tip-recorded
      potential reflects correctly the relative variations of the dendritic membrane
      potential as a function of stimulus intensity over a large range of parameters.
      The geometric and electrical characteristics of the sensillum that need be known
      to compute the dendritic membrane potential from the tip-recorded potential are
      given.

PMID- 11288835
TI  - Rotational dynamics of curved DNA fragments studied by fluorescence polarization
      anisotropy.
AB  - The rotational dynamics of short DNA fragments with or without intrinsic
      curvature were studied using time-resolved phase fluorimetry of intercalated
      ethidium with detection of the anisotropy. Parameters determined were the
      spinning diffusion coefficient of the DNA fragments about the long axis and the
      zero-time ethidium fluorescence anisotropy. We find a significant decrease in the
      spinning diffusion coefficient for all curved fragments compared to the straight
      controls. This decrease is likewise evident in rotational diffusion coefficients
      computed from DNA structures obtained by a curvature prediction program for these
      sequences. Using a hinged-cylinder model, we can identify the change in
      rotational diffusion coefficient with a permanent bend of 13-16 degrees per helix
      turn for the sequences studied. Moreover, for some of the curved fragments an
      increased flexibility has to be assumed in addition to the permanent bend in
      order to explain the data.

PMID- 11288836
TI  - Effects of semiconductor substrate and glia-free culture on the development of
      voltage-dependent currents in rat striatal neurones.
AB  - An essential requirement for successful long-term coupling between neuronal
      assemblies and semiconductor devices is that the neurones must be able to fully
      develop their electrogenic repertoire when growing on semiconductor (silicon)
      substrates. While it has for some time been known that neurones may be cultured
      on silicon wafers insulated with SiO2 and Si3N4, an electrophysiological
      characterisation of their development under such conditions is lacking. The
      development of voltage-dependent membrane currents, especially of the rapid
      sodium inward current underlying the action potential, is of particular
      importance because the conductance change during the action potential determines
      the quality of cell-semiconductor coupling. We have cultured rat striatal
      neurones on either glass coverslips or silicon wafers insulated with SiO2 and
      Si3N4 using both serum-containing and serum-free media. We here report evidence
      that not only serum-free culture media but also growth on semiconductor surfaces
      may negatively affect the development of voltage-dependent currents in neurones.
      Furthermore, using surface-charge measurements with the atomic force microscope,
      we demonstrate a reduced negativity of the semiconductor surface compared to
      glass. The reduced surface charge may affect cellular development through an
      effect on the binding and/or orientation of extracellular matrix proteins, such
      as laminin. Our findings therefore suggest that semiconductor substrates are not
      entirely equivalent to glass in terms of their effects on neuronal cell growth
      and differentiation.

PMID- 11288837
TI  - A short-run new analytical ultracentrifugal micromethod for determining low
      density lipoprotein sub-fractions using Schlieren refractometry.
AB  - We have developed a new analytical ultracentrifugal micromethod for the
      determination of serum low-density lipoprotein (LDL) subclasses directly from
      ultracentrifugal Schlieren scans. We have used special software for the analysis
      of this type of single-spin density-gradient ultracentrifugation. The flotation
      of LDL patterns was obtained by underlayering a physiological salt solution with
      serum or isolated lipoprotein fractions raised to a density of 1.3 g/mL in the
      spinning ultracentrifugation capillary band-forming cell. The repeated analysis
      of Schlieren curves of the same sample from 10 to 100 microL in the 60-100 min
      full-speed interval time resulted in quite reproducible results. We obtained
      quantitative results by measuring the Schlieren areas between the sample curves
      and the reference baseline curve by using computerised numerical and graphic
      techniques. The decomposition of the integrated curve was carried out using a
      nonlinear regression program followed by deconvolution algorithm analysis in
      order to determine the parameters of the composing Gaussian subclasses. The LDL
      particle concentrations were calculated from the area under the integral of the
      Gaussian curve using a calibration data constant. The flotation range of the LDL
      Schlieren curves in the cell was identified with serum from which LDL had been
      removed by means of precipitation reagents and with centrifugation of isolated
      LDL aliquots. With this technique, we measured the concentration of LDL and
      analysed its polydispersity without the need for preceding sequential isolation
      of the LDL. On the basis of the Schlieren curves, the LDL samples were either
      physically paucidisperse, having a symmetrical peak within a narrow density
      range, or were polydisperse, showing an asymmetrical pattern distributed over a
      broader density region. The described method proved to be useful for a clear and
      immediate visual presentation of the concentration values of the LDL and for the
      identification of the heterogeneity of LDL variants without the need for the
      preparative isolation of that density class.

PMID- 11288838
TI  - The role of retinal in the long-range protein-lipid interactions in
      bacteriorhodopsin-phosphatidylcholine vesicles.
AB  - The effects of bacteriorhodopsin analogues and the analogues of a
      bacteriorhodopsin mutant (D96N) on the lateral organization of lipids have been
      investigated with lipid species with a variety of acyl chain lengths. The
      analogues, obtained by regeneration of bacterioopsin or mutant opsin with 14-, 12
      , 10-, or 8-fluororetinal, were reconstituted with 1,2-didodecanoyl-sn-glycero-3
      phosphocholine, 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine, 1,2
      dihexadecanoyl-sn-glycero-3-phosphocholine, and 1,2-dioctadecanoyl-sn-glycero-3
      phosphocholine. The phase behavior of the protein-lipid systems was investigated
      at different temperatures and different protein/lipid molar ratios by analyzing
      the fluorescence and phase properties of the 1-acyl-2-[8-(2-anthroyl)octanol]-sn
      glycero-3-phosphocholine probe. The (8,10,12)-bacteriorhodopsins had a similar
      effect on the lipid phase transition to that induced by native bacteriorhodopsin:
      a rigidifying effect on the three shorter lipid species and a fluidifying effect
      on the longest-chain lipids used. The substitution of retinal with 14
      fluororetinal resulted in much stronger effects of the protein on the lipids: a
      more pronounced up-shift of the lipid phase transition temperature, a rigidifying
      effect on all the lipids used, and an elongation of the distance over which the
      hydrophobic thickness of the lipid bilayer was perturbed by the protein. Evidence
      was provided that retinal contributed to the long-range protein-lipid
      interactions in bacteriorhodopsin-phosphatidylcholine vesicles. The extent of
      this contribution was dependent on the retinal structure in close vicinity to the
      Shiff base and on the compactness of the protein structure.

PMID- 11288839
TI  - MR urography: examination techniques and clinical applications.
AB  - Modern MR urography is performed on the basis of two different imaging
      strategies, which can be used complementarily to cover almost all aspects in the
      diagnosis of upper urinary tract diseases. The first technique utilizes
      unenhanced, heavily T2-weighted pulse sequences to obtain static-fluid images of
      the urinary tract. T2-weighted MR urograms have proved to be excellent in the
      visualization of the markedly dilated urinary tract, even if the renal excretory
      function is quiescent. Static-fluid MR urography is less suitable for imaging of
      disorders that occur in the nondilated collecting system. The second MR urography
      technique is analogous to the methodology of conventional intravenous pyelography
      and is, therefore, designated as excretory MR urography. For this purpose, a non
      nephrotoxic gadolinium chelate is intravenously administered and after its renal
      excretion, the gadolinium-enhanced urine is visualized using fast T1-weighted
      gradient-echo sequences. The combination of gadolinium and low-dose furosemide (5
      10 mg) is the key for achieving a uniform distribution of the contrast material
      inside the entire urinary tract and, secondly, to avoid high endoluminal
      gadolinium concentrations, which cause signal loss of the urine due to T2*
      effects. Gadolinium excretory MR urography allows to obtain high-quality images
      of both nondilated and obstructed urinary tracts in patients with normal or
      moderately impaired renal function. This article reviews the principles of T2-
      and T1-weighted MR urography in detail and informs how to use these techniques
      safely in potential clinical applications such as chronic urolithiasis, intrinsic
      and extrinsic tumor diseases, and congenital anomalies. Magnetic resonance
      urography performed in combination with standard MR imaging offers a potential to
      reduce the need for invasive retrograde pyelography. Although the economic aspect
      is still problematic, it is obvious that MR urography will continue to increase
      its role in clinical uroradiology.

PMID- 11288840
TI  - High-resolution CT of diffuse interstitial lung disease: key findings in common
      disorders.
AB  - High-resolution CT (HRCT) is the radiological imaging technique that most closely
      reflects changes in lung structure. It represents the radiological method of
      choice for the diagnostic work-up of patients with known or suspected diffuse
      interstitial lung disease. A single HRCT finding is frequently nonspecific, but
      the combination of the various HRCT findings together with their anatomic
      distribution can suggest the most probable diagnosis. The purpose of this article
      is to summarize the classic HRCT features of the most common diffuse interstitial
      lung diseases. Lists of differential diagnoses and distinguishing key features
      are provided to improve diagnostic confidence. The presence of classic HRCT
      features often obviates the need for biopsy. In patients with atypical findings,
      HRCT can be used to determine the most appropriate biopsy site.

PMID- 11288841
TI  - Paired inspiratory-expiratory thin-section CT findings in patients with small
      airway disease.
AB  - The objective of this study was to evaluate minimal small airway disease (SAD) as
      reflected on paired inspiratory-expiratory CT findings. Seventy-two subjects, 34
      with SAD, 11 with normal lung function, and 27 with chronic obstructive pulmonary
      diseases (COPD), underwent thin-section CT during deep inspiration and expiration
      at upper, middle, and lower lung levels. Evaluation of CT measurement was
      performed between inspiratory and expiratory CT attenuation of lung parenchyma,
      in non-dependent and dependent lung at each of the three levels. Visual
      assessment of mosaic patterns and attenuation differences was also performed
      using the inspiratory and expiratory images. Patients with SAD were
      differentiated from those with COPD, by visual assessment and from the CT
      measurements. Visual assessment failed to differentiate between the SAD and
      normal groups. However, one measurement, an inspiratory-expiratory attenuation
      difference in the dependent lower lung, was different between SAD and normal
      group. Early small airway disease may be indicated by an inspiratory-expiratory
      attenuation difference in the dependent lower lung using the simple method of a
      paired inspiratory-expiratory CT.

PMID- 11288842
TI  - Thin-section CT vs spiral CT in candidates for lung volume reduction surgery: a
      comparison based on radiologists' subjective preferences.
AB  - The aim of this study was to investigate whether high-resolution (HRCT) or spiral
      CT was preferred in evaluating severe emphysema in patients undergoing lung
      volume reduction surgery (LVRS), whether there is any difference in this regard
      between the cranial and caudal part of the lung, and whether the degree of
      emphysema has an impact on the radiologists' preference. The study was performed
      by letting four radiologists compare images obtained with the two techniques
      (film pairs) and decide which technique they preferred or if the techniques were
      considered as equal in evaluating emphysema. In evaluation of 188 film pairs, the
      HRCT images were preferred in 56 %, spiral CT in 19 % and the techniques
      considered as equal in 25 %. Spiral CT images were preferred more often in the
      caudal part of the lung and in more advanced emphysema compared with the HRCT
      images. The study confirms our clinical assumption that use of both CT techniques
      are valuable in evaluating advanced emphysema and there may be technical as well
      as histopathological reasons for this.

PMID- 11288843
TI  - Blunt traumatic rupture of a mainstem bronchus: spiral CT demonstration of the
      "fallen lung" sign.
AB  - Tracheo-bronchial injuries occur in less than 1 % of blunt chest trauma patients.
      Indirect signs, such as pneumomediastinum, pneumothorax, and/or subcutaneous
      emphysema, are revealed on admission plain films and chest CT survey. In most
      instances, however, tracheobronchoscopy is mandatory in assessing the definite
      diagnosis of tracheo-bronchial lesion. Occasionally, an abnormal course of a
      mainstem bronchus or a "fallen lung" sign, featuring a collapsed lung in a
      dependent position, hanging on the hilum only by its vascular attachments, may
      allow for CT diagnosis of a blunt traumatic bronchial injury.

PMID- 11288844
TI  - Intraluminal penetration of the band in patients with adjustable silicone gastric
      banding: radiological findings.
AB  - The aim of this study was to analyse radiological findings in patients surgically
      treated for adjustable silicone gastric banding (ASGB) for morbid obesity
      complicated by band penetration into the gastric lumen. We reviewed the records
      of four patients with surgically confirmed penetration of gastric band into the
      gastric lumen; three had preoperative opaque meal, one only a plain abdominal
      film. Vomiting was the presenting symptom in two cases, whereas others had new
      weight gain and loss of early satiety. Two patients had normally closed bands:
      radiography showed that their position had changed from previous controls and the
      barium meal had passed out of their lumen. Two patients had an open band. One
      patient had the band at the duodeno-jejunal junction, and the tube connecting the
      band to the subcutaneous port presented a winding course suggesting the duodenum.
      In the other case, both plain film and barium studies failed to demonstrate with
      certainty the intragastric position of the band. As ASGB is becoming widely used,
      radiologists need to be familiar with its appearances and its complications. Band
      penetration into the stomach is a serious complication which needs band removal.
      Patients with this problem, often with non-specific symptoms and even those who
      are asymptomatic, are encountered during radiographic examinations requested
      either for gastric problems or follow-up purposes, and have to be properly
      diagnosed.

PMID- 11288845
TI  - Spontaneous volume changes in gastric banding devices: complications of a
      semipermeable membrane.
AB  - The goal of this study was to prove that adjustable laparoscopic gastric banding
      (LAP-BAND) is semipermeable and that luminal adjustment with saline leads to
      spontaneous fluid loss, luminal widening, and effect loss which makes repeated
      readjustments necessary. In 64 patients stoma adjustment was performed with
      saline according to the guidelines of the manufacturer (group 1). In 32 patients
      hyperosmolar contrast material was used for stoma readjustments with the
      intention to detect a system leakage after spontaneous fluid loss and spontaneous
      luminal widening was observed (group 2). After spontaneous luminal narrowing had
      occurred in group 2, all patients from group 2 and all additional patients (n =
      148) underwent stoma (re-) adjustment with iso-osmolar contrast material (group
      3). Spontaneous fluid changes which led to spontaneous changes of the luminal
      width were then analyzed for the different filling substances in each group.
      Fifty-two patients from group 1 presented with effect loss because a spontaneous
      luminal widening had occurred secondary to a fluid loss of 0.1-0.2 ml/month. All
      32 patients from group 2 presented with increasing obstruction and food
      intolerance because a spontaneous luminal narrowing had occurred secondary to a
      spontaneous fluid gain of 0.1-0.3 ml/month. In our patients from group 3, where
      stoma adjustment was performed with iso-osmolar contrast material, no spontaneous
      fluid changes were observed and luminal width/degree of obstruction did not
      change. The LAP-BAND is semipermeable. Stoma adjustment should not be performed
      with saline in order to avoid spontaneous luminal widening and the need for
      repeated readjustments. Stoma adjustments with hyperosmolar contrast material are
      clearly contraindicated since osmotic fluid gain leads to increasing obstruction.
      Stoma adjustments should be performed using iso-osmolar filling media which
      provide a stable luminal obstruction.

PMID- 11288846
TI  - Lesser sac hematoma as a sign of rupture of hepatocellular carcinoma in the
      caudate lobe.
AB  - The purpose of this study was to evaluate the CT findings of rupture of
      hepatocellular carcinoma (HCC) in the caudate lobe of the liver. The CT scans of
      five cases of rupture of HCC in the caudate lobe of the liver were
      retrospectively reviewed and correlated with clinical records. All cases showed
      exophytic tumors in the caudate lobe of the liver and high-attenuation hematomas
      in the lesser sac on CT. A lesser sac hematoma may be a sentinel clot sign of
      rupture of HCC in the caudate lobe.

PMID- 11288848
TI  - Dose reduction in evacuation proctography.
AB  - The goal of this study was to reduce the patient radiation dose from evacuation
      proctography. Ninety-eight consecutive adult patients referred for proctography
      to investigate difficult rectal evacuation were studied using a digital imaging
      system with either a standard digital program for barium examinations, a reduced
      dose digital program (both with and without additional copper filtration), or
      Video fluoroscopy. Dose-area products were recorded for each examination and the
      groups were compared. All four protocols produced technically acceptable
      examinations. The low-dose program with copper filtration (median dose 382 cGy
      cm2) and Video fluoroscopy (median dose 705 cGy cm2) were associated with
      significantly less dose than other groups (p < 0.0001). Patient dose during
      evacuation proctography can be reduced significantly without compromising the
      diagnostic quality of the examination. A digital program with added copper
      filtration conveyed the lowest dose.

PMID- 11288847
TI  - Biphasic spiral CT of the liver: automatic bolus tracking or time delay?
AB  - The aim of this study was to evaluate the value of automatic bolus tracking for
      biphasic spiral CT of the liver in comparison with time delay examinations. Forty
      patients scheduled for a biphasic spiral CT of the liver randomly were examined
      either with time delay of 25 s for the arterial phase and 55 s for the portal
      venous phase (n = 20), or with an automatic scan start triggered by contrast
      enhancement in the aorta (n = 20). Examinations were performed with 120 ml of
      contrast material and a flow rate of 4.0 ml/s. Density measurements of the aorta,
      of the liver parenchyma, and of the spleen were obtained by means of regions of
      interest (ROI). The end of the arterial phase was considered when hepatic
      parenchymal enhancement was greater than 20 HU. In all patients of the group with
      automatic bolus tracking arterial scanning was completed in the arterial phase of
      the liver. In 25 % of patients with fixed time delay, however, an enhancement of
      liver parenchyma during arterial phase greater than 20 HU was observed. During
      the portal-venous phase there was no significant difference in parenchymal
      enhancement between both groups. Automatic bolus tracking allows an
      individualized timing of the arterial phase in biphasic spiral CT of the liver.
      The timing is more accurate than in time delay scanning.

PMID- 11288849
TI  - Treatment of a malignant stenosis of the corpus of the stomach with a self
      expanding stent.
AB  - In a 50-year-old man, a self-expandable stent was implanted under fluoroscopic
      guidance to treat symptoms of an inoperable carcinoma of the corpus of the
      stomach. Foreshortening of the stent necessitated implantation of a proximal
      extension stent 5 weeks later. Secondary symptoms of advanced stage of the
      disease negatively influenced clinical success of the procedure, although free
      passage through the stents was achieved. We conclude that stent implantation for
      palliation of a carcinoma of the corpus of the stomach seems to be a viable
      method. The operator has to be aware of the special limitations and problems
      associated with the procedure.

PMID- 11288850
TI  - Thrombolysis in the peripheral vascular system.
AB  - The technique of thrombolysis is now well established, becoming employed
      increasingly often in disease of the peripheral vasculature, both arterial and
      venous, in addition to its important role in the treatment of coronary artery
      thrombosis. This is a general review of its applications in peripheral vascular
      disease causing acute lower limb ischaemia, currently the major indication for
      its use outside the coronary circulation.

PMID- 11288851
TI  - Magnetic resonance angiography: the state of the art.
AB  - Three-dimensional contrast magnetic resonance angiography has rapidly advanced
      over recent years. It is now a highly accurate and safe method of diagnosing
      vascular abnormalities of the thoracic, abdominal and peripheral vessels. We
      describe techniques for the examination of the thoracic and abdominal aorta, the
      renal arteries and the lower limb vessels together with strategies to improve
      their diagnostic accuracy.

PMID- 11288852
TI  - A new vascular sealant (Sealgel) to achieve rapid hemostasis after percutaneous
      angioplasty in anticoagulated patients: clinical feasibility and preliminary
      results.
AB  - The aim of this study was to assess the feasibility of a new vascular sealant
      (Sealgel) to provide rapid hemostasis in anticoagulated patients after
      percutaneous transluminal angioplasty (PTA). Sealgel was designed with ancrod (10
      mg) and tranexamic acid (80 mg) dissolved in a hyaluronic acid gel (3 ml). Fifty
      anticoagulated patients (heparin, aspirin, ticlopidin) who underwent PTA of
      coronary artery were enrolled in the study. Sealgel (3 ml) was delivered under
      manual compression through a 9-F cannula at the arterial puncture site after the
      introducer sheath removal at the end of PTA procedure. Hemostasis time as well as
      complications were recorded. Sealgel was successfully delivered in 98 % of
      patients. Hemostasis occurred within 15 mn of manual compression in 82 % of
      patients, within 25 mn in 98 %, and failed in 1 patient (2 %). Hematoma (6-cm
      diameter) was observed in 1 patient and late bleeding in another one. There were
      no clinical signs of embolism, inflammatory swelling, local infection, vascular
      fistula, or pseudoaneurysm. No surgery or blood transfusion was required. Sealgel
      application after PTA in anticoagulated patient is feasible and secure.
      Preliminary results suggest that the Sealgel brought about rapid hemostasis;
      however further studies are needed to determine its clinical efficacy.

PMID- 11288853
TI  - Imaging recurrent parosteal osteosarcoma.
AB  - The aim of this study was to document the imaging features of recurrent parosteal
      osteosarcoma. The clinical and imaging records of 33 patients with a parosteal
      osteosarcoma referred to an orthopaedic oncology service over a 17-year period
      were retrospectively reviewed. The mode of identification of locally recurrent
      tumour was noted, together with the management and clinical outcome. Five
      patients developed a local recurrence of their parosteal osteosarcoma ranging
      from 6 months to 10 years after initial surgery. In 4 patients the recurrence was
      first suspected clinically due to the development of a mass. In the fifth patient
      recurrence was first detected on routine follow-up radiography. In 4 patients the
      recurrence could be identified on radiography as a mineralized mass. All the
      recurrences were readily identified on MR imaging, despite artefacts from
      prostheses. The recurrences were also evident in the 3 cases in which bone
      scintigraphy was performed. Local recurrence of parosteal osteosarcoma is
      adequately detected with a combination of clinical examination and conventional
      radiography. MR imaging is required to stage local recurrence or where
      radiography has failed to confirm clinically suspected recurrence. The routine
      use of MR imaging to follow-up patients is of doubtful value because of the
      frequently long time between initial surgery and relapse.

PMID- 11288854
TI  - Neurologic dysfunction in patients with rheumatoid arthritis of the cervical
      spine. Predictive value of clinical, radiographic and MR imaging parameters.
AB  - The aim of this study was to evaluate if subjective symptoms, radiographic and
      especially MR parameters of cervical spine involvement, can predict neurologic
      dysfunction in patients with severe rheumatoid arthritis (RA). Sequential
      radiographs, MR imaging, and neurologic examination were performed yearly in 46
      consecutive RA patients with symptoms indicative of cervical spine involvement.
      Radiographic parameters were erosions of the dens or intervertebral joints, disc
      space narrowing, horizontal and vertical atlantoaxial subluxation, subluxations
      below C2, and the diameter of the spinal canal. The MR features evaluated were
      presence of dens and atlas erosion, brainstem compression, subarachnoid space
      encroachment, pannus around the dens, abnormal fat body caudal to the clivus,
      cervicomedullary angle, and distance of the dens to the line of McRae. Muscle
      weakness was associated with a tenfold increased risk of neurologic dysfunction.
      Radiographic parameters were not associated. On MR images atlas erosion and a
      decreased distance of the dens to the line of McRae showed a fivefold increased
      risk of neurologic dysfunction. Subarachnoid space encroachment was associated
      with a 12-fold increased risk. Rheumatoid arthritis patients with muscle weakness
      and subarachnoid space encroachment of the entire cervical spine have a highly
      increased risk of developing neurologic dysfunction.

PMID- 11288855
TI  - Melorheostosis: a review of 23 cases.
AB  - The aim of this study was to review clinical and radiological signs of
      melorheostosis in a large series of cases. Family history, patient history,
      clinical data and radiological features of 23 consecutive cases of melorheostosis
      were investigated. Criteria for establishing the diagnosis "melorheostosis" were
      defined. Sixteen patients (mean age 34 years, equal ratio between genders) had
      chronic pain in the affected limb(s) and/or subcutaneous fibrosis and/or various
      skin lesions. Number of involved bones: one bone (n = 10); two bones (n = 4);
      three or more bones (n = 9). Anatomic distribution: upper extremity (n = 5);
      lower extremity (n = 16); upper and lower extremity (n = 1); sacrum (n = 1).
      Radiologic pattern: osteoma-like (n = 7); classic candle wax appearance (n = 5);
      myositis ossificans-like (n = 1); osteopathia striata-like (n = 6); mixed pattern
      (n = 4). Patterns different from the appearance formerly judged to be "classic"
      prevail. The standard concept of disease manifestation has to be adjusted.
      Pathogenesis remains unclear. The classic theory claims the presence of an early
      embryonic infection of a sensory nerve inducing changes in the respective
      sclerotome, but we propose the concept of mosaicism as a better explanation for
      the sporadic occurrence, the asymmetric "segmental" pattern with variable extent
      of involvement and equal gender ratio of the disease.

PMID- 11288856
TI  - Recurrent massive subperiosteal hematoma in a patient with neurofibromatosis.
AB  - The authors report the case of a 13-year-old neurofibromatosis (NF-I) patient who
      suffered a blunt trauma in 1993. The diagnosis of subperiosteal hematoma was
      made. The pathogenesis of subperiosteal hematoma is discussed.

PMID- 11288857
TI  - Imaging dementias.
AB  - Dementia is the progressive loss of intellectual functions due to involvement of
      cortical or subcortical areas. Specific involvement of certain brain areas in the
      different diseases leads to impairment of different functions, e. g., memory,
      language, visuospatial abilities, and behavior. Magnetic resonance imaging and
      other neuroradiological studies may indicate which structures are mainly or
      selectively involved in a demented patient, thus allowing clinical-radiological
      correlations. Clinical presentation and evolution of the disease, supported by
      imaging studies, may lead to a highly probable diagnosis. The most common
      disorders, or the most relevant from the neuroradiological point of view, such as
      Alzheimer's disease, frontotemporal dementia, vascular dementias, dementia
      associated with parkinsonism, Huntington's disease, Creutzfeldt-Jakob disease,
      and normal-pressure hydrocephalus, are briefly discussed.

PMID- 11288858
TI  - Association of cerebral arteriovenous malformation with cerebral arterial
      fenestration.
AB  - Cerebral arteriovenous malformations (AVMs) are rarely associated with other
      vascular lesions. Our goal was to examine the incidence of the coexistence of
      cerebral AVMs and cerebral arterial fenestrations. During the past 18 years, 51
      patients with a cerebral AVM were examined with selective cerebral angiography in
      our institution. We retrospectively reviewed these cerebral angiographies and
      noted associated cerebral arterial fenestrations. We found five fenestrations
      distributed among 3 patients. In each patient one fenestration was located in the
      vertebral artery (VA). In 1 patient there were additional basilar and left middle
      cerebral artery fenestrations. Vertebral artery angiography was performed in 43
      of the 51 patients; thus, the frequency of coexistence of AVM and VA fenestration
      was 7% (3 of 43). Although the clinical significance may not be great, we found a
      noteworthy incidence of associated VA fenestrations in AVM cases.

PMID- 11288859
TI  - MR spectrum in spinal dysraphism.
AB  - Spinal dysraphism is a general term which encompasses a wide variety of anomalies
      of the spine, all of which result from imperfect midline fusion of the embryonic
      neural tube. This term refers to large defects that involve the spine and not to
      small vertical clefts commonly seen within the spinal process of L5 or S1. We
      present a spectrum of MR imaging findings selected from a retrospective review of
      100 patients of spinal dysraphism evaluated at our institution.

PMID- 11288860
TI  - Integrated diagnostic imaging of primary thoracic rhabdomyosarcoma.
AB  - We report a rare case of primary thoracic rhabdomyosarcoma in a girl who was
      referred with acute chest pain, hacking cough, and wheezing. A chest X-ray
      revealed a complete opacity of the right hemithorax. Ultrasound revealed a right
      sided pleural effusion and a solid mass above the liver dome, suggesting a
      neoplastic disease, which quickly led to further specific examination. Use of CT
      and MRI together with bone scintigraphy completed the investigation. The biopsy
      specimen showed a pattern of alveolar rhabdomyosarcoma. This case was reported to
      emphasize the role of US in the evaluation of a child with hemithorax opacity.

PMID- 11288861
TI  - Accessory spleen torsion: US, CT and MR findings.
AB  - Torsion of an accessory spleen is a very unusual entity that can appear with
      abdominal pain associated with the presence of an avascular mass. We report the
      case of a 13-year-old boy with torsion and infarction of an accessory spleen
      presenting as a painful abdominal mass in which imaging examination with US, CT
      and MR showed a large avascular mass in the upper left abdomen.

PMID- 11288862
TI  - Year 2000: status of picture archiving and digital imaging in European hospitals.
AB  - The aim of this study was to compare the degrees of implementations of full and
      departmental Picture Archiving and Communication Systems (PACS), the usage of
      mini-PACS and to compare digital image equipment implementation rates in the
      countries of the European Union plus the Czech Republic, Cyprus, Malta, Norway,
      Poland and Switzerland. The degree to which Digital Image Communications in
      Medicine version 3.0 (DICOM 3.0) protocols are available for data exchange by
      different digital image equipment is surveyed, to assess underlying PACS
      preparedness. A questionnaire with an addressed reply envelope was posted to the
      heads of radiology of 1,594 hospitals in 19 countries in early 2000. Data returns
      were obtained from 17 countries. This indicates considerable variation in PACS
      implementation and preparedness between European nations. Possible reasons for
      this are discussed. The highest rates of PACS implementations have been in
      Austria, Norway and Sweden.

PMID- 11288863
TI  - Autonomous pelvi-ureteric peristalsis in renal transplants confirmed by color
      Doppler mapping of the jet phenomenon.

PMID- 11288864
TI  - Quiz case of the month. Solitary fibrous tumour of the pleura.

PMID- 11288865
TI  - Hierarchically imprinted sorbents.
AB  - A double imprinting methodology was developed to synthesize novel materials with
      hierarchical structures. On the microporous level (1-3 A), metal ions served as
      template. On the mesoporous level (diameters of 25-40 A), micellar structures
      produced by self-assembly of surfactant molecules were used as templates. Removal
      of both metal ions and surfactant micelles resulted in the formation of imprints
      with different sizes within the silica matrix, each with a specific function.
      This research opens vast opportunities for the applications of ordered mesoporous
      materials in the area of molecular recognition such as separations, chemical
      sensors, and catalysts.

PMID- 11288866
TI  - Systematics in the enthalpies of formation of anhydrous aluminosilicate zeolites,
      glasses, and dense phases.

PMID- 11288867
TI  - 1-Boraadamantane: reactivity towards di(1-alkynyl)silicon and -tin compounds:
      first access to 7-metalla-2,5-diboranorbornane derivatives.
AB  - 1-Boraadamantane (1) reacts with di(1-alkynyl)silicon and -tin compounds 2
      (Me2M(C...CR)2: M=Si; R=Me (a), tBu (b), SiMe3 (c); M=Sn, R=SiMe3 (e)) in a 1:1
      ratio by intermolecular 1,1-alkylboration, followed by intramolecular 1,1
      vinylboration, to give siloles 5a-c and the stannole 5e, respectively, in which
      the tricyclic 1-boraadamantane system is enlarged by two carbon atoms. Owing to
      the high reactivity of 1, a second fast intermolecular 1,1-alkylboration competes
      with the intramolecular 1,1-vinylboration as the second major step in the
      reaction if the substituent R at the C...C bond is small (2a) and/or if the M
      C... bond is also highly reactive, as in 2d (M=Sn, R= Me) and 2e (M=Sn, R=SiMe3).
      This leads finally to the novel octacyclic 7-metalla-2,5-diboranorbornane
      derivatives 8a, 8d, and 8e, of which 8e was characterized by X-ray analysis in
      the solid state. 1,1,2,2-Tetramethyldi(1-propynyl)disilane, MeC...C-SiMe2SiMe2
      C...CMe (3), reacts with 1 to give mainly a 1,2-dihydro-1,2,5-disilaborepine
      derivative 9 and the octacyclic compound 11, which is analogous to 8a but with an
      Me4Si2 bridge. All new products were characterized in solution by 1H, 11B, 13C,
      29Si, and 119Sn NMR spectroscopy. For 8 and 11, highly resolved 29Si and 119Sn
      NMR spectra revealed the first two-bond isotope-induced chemical shifts,
      2delta10/11B(29Si) and 2delta10/11B(119Sn) respectively, to be reported.

PMID- 11288868
TI  - Syntheses and molecular structures of new cali.
AB  - An unusual disproportionation reaction of the molybdenum(IV) and tungsten(IV)
      chlorides [MCl4L2] (M=Mo, L=Et2S, Et2O; M=W; L= Et2S) in the presence of p-tBu
      calix[4]arene (Cax(OH)4) and triethylamine leads to d0 complexes
      [(CaxO4)[CaxO2(OH)2]M] (1) and d3 compounds (HNEt3)2[(CaxO4)2M2] (2). Complexes
      la (M = Mo), 1b (M = W), and the HCl adduct of 2a (M = Mo) have been structurally
      characterized. Compound 1a represents one of the few examples of a well
      characterized molybdenum(VI) hexa-alkoxide complex of the type [Mo(OR)6].
      Isolation and structural characterization of the side product [(CaxO4W)[kappa2(O)
      kappa1(O)-CaxO3(OH)](CaxO4WCl)] (3) suggests the intermediacy of chloro
      containing calix[4]arene complexes in these reaction mixtures. The reaction of 1a
      with HCI provides [CaxO4MoCl2] (4a), the first well-defined example of a mixed
      molybdenum(VI) alkoxide halide compound of the general formula [MoClx(OR)6-x].

PMID- 11288869
TI  - The importance of mesomerism in the termination of alpha-carboxymethyl radicals
      from aqueous malonic and acetic acids.
AB  - In the dioxygen-free aqueous malonic and acetic acid systems. alpha-carboxymethyl
      radicals are produced through hydrogen abstraction from the parent compound by
      radiolytically generated OH radicals. H abstraction from the CO2-/CO2H group
      followed by decarboxylation is a process of small importance (< or = 5%). The
      alpha-carboxymethyl radicals terminate by recombination. Two types of
      recombination product are observed which are characterised by the formation of a
      C-C linkage or a C-O linkage. alpha-Carboxymethyl radicals are mesomeric systems.
      Their mesomeric state depends on the state of protonation and determines the
      proportion of the C-C- versus C-O-linked dehydrodimers they produce.

PMID- 11288870
TI  - A common carbanion intermediate in the recombination and proton-catalysed
      disproportionation of the carboxyl radical anion, CO2*-, in aqueous solution.
AB  - The carboxyl radical anion, CO2*- was produced by the reactions of OH radicals
      with either CO or formic acid in aqueous solution. The pKa(*CO2H) was determined
      by pulse radiolysis with conductometric detection at pH approximately equals 2.3.
      The bimolecular decay rate constant of CO2*- (2k approximately equals 1.4 x 10(9)
      dm3mol(-1)s(-1)) was found to be independent of pH in the range 3-8 at constant
      ionic strength. The yields of the products of the bimolecular decay of the
      carboxyl radicals, CO2 and the oxalate anion were found to depend strongly on the
      pH of the solution with an inflection point at pH 3.8. This pH dependence is
      explained by assuming a head-to-tail recombination of the CO2*- radicals followed
      by either rearrangement to oxalate or a protonation of the adduct, which
      subsequently leads to the formation of CO2 and formate. The recombination of CO2*
      to give oxalate directly is estimated to have a contribution of <25%.

PMID- 11288871
TI  - A possible mechanism for enantioselectivity in the chiral epoxidation of olefins
      with.
AB  - The origin of enantioselectivity in the Jacobsen-Katsuki reaction has been
      investigated by applying density functional calculations in combination with
      molecular mechanics methodologies. The calculations suggest that a high
      enantiomeric excess is connected to three specific features: 1) a chiral diimine
      bridge, which induces folding of the salen ligand(H2salen =
      bis(salicylidene)ethylenediamine), and hence the formation of a chiral pocket; 2)
      bulky groups at the 3,3'-positions of the salen ligand, which cause a
      preferential approach from the side of the aromatic rings; and 3) pi conjugation
      of the olefinic double bond, which confers regioselectivity and, consequently,
      enantioselectivity. In combination with experimental studies, the model also
      provides a rationale for the decrease in ee values when one of these components
      is missing.

PMID- 11288872
TI  - Towards a better understanding of the cisplatin mode of action.
AB  - We have studied how platinum(II) complexes [Pt(dien)Cl]Cl, [Pt(en)Cl2] and
      cisplatin react with hybrid molecules that contain sulfur and nitrogen ligands,
      in particular Phac-Met-linker-p5'dG (Phac = phenylacetyl), Phac-His-linker-p5'dG,
      Phac-His-Met-linker-p5'dG and Phac-His-Gly-Met-linker-p5'dCATGGCT. The progress
      of the reactions was monitored by HPLC, and by [1H,15N]-HSQC NMR when 15N
      cisplatin was used. The products were isolated and characterised by using
      enzymatic and chemical reactions and spectroscopic techniques (UV and/or NMR
      spectroscopy, electrospray or MALDI-TOF mass spectrometry). The combined use of
      digestion with proteases and reaction with hydrogen peroxide followed by mass
      spectrometric analysis indicated the platinum coordination positions on the
      peptide moiety of the largest hybrid. Monofunctional Pt-S adducts were
      transformed into Pt-N complexes in which Pt-N7 bonds were formed preferentially.
      Most of the chelates isolated had Pt-S bonds, and, in the case of cisplatin
      complexes, loss of the ammine trans to sulfur gave rise to the formation of
      tricoordinate species with platinum-mediated peptide-nucleotide cross-links. 1,2
      Intrachain platinum GpG adducts were only obtained in very small amounts (1-4%).

PMID- 11288873
TI  - Efficient charge separation in porphyrin-fullerene-ligand complexes.
AB  - Photoprocesses associated with the complexation of a pyridine-functionalized C60
      fullerene derivative to ruthenium- and zinc-tetraphenylporphyrins (tpp) have been
      studied by time-resolved optical and transient EPR spectroscopies. It has been
      found that upon irradiation in toluene, a highly efficient triplet-triplet energy
      transfer governs the deactivation of the photoexcited [Ru(tpp)], while electron
      transfer (ET) from the porphyrin to the fullerene prevails in polar solvents.
      Complexation of [Zn(tpp)] by the fullerene derivative is reversible and,
      following excitation of the [Zn(tpp)], gives rise to very efficient charge
      separation. In fluid polar solvents such as THF and benzonitrile, radical-ion
      pairs (RPs) are generated both by intramolecular ET inside the complex and by
      intermolecular ET in the uncomplexed form. Charge-separated states have lifetimes
      of about 10 micros in THF and several hundred of microseconds in benzonitrile at
      room temperature.

PMID- 11288874
TI  - Nucleobase-containing metallated polymeric resins as artificial
      phosphodiesterases: kinetics of hydrolysis, pH dependence, and catalyst
      recycling.
AB  - Two metallated polymeric resins that contain the nucleobase adenine have been
      investigated for their ability to catalyze the hydrolysis of model phosphodiester
      substrates. These resins behave in a catalytic manner and display classical
      Michaelis-Menten kinetics. Consequently, parameters such as kobs, Km, Vmax, and
      kcat were determined for the two resins for both of the substrates. The most
      attractive feature of our nucleolytic system is its facile reusability that
      permits catalysis of multiple hydrolytic reactions, after resin recovery and a
      simple washing step, without significantly compromising the reaction rate.
      Involvement of a hydrolytic mechanism for phosphodiester cleavage is proposed on
      the basis of pH versus hydrolytic rate profiles for the two resins. We have also
      been able to demonstrate temperature-dependence, solvent effects, and inhibitory
      nature of vanadate ions on the observed rate of hydrolytic reaction aided by the
      resins. In conclusion, metallated nucleobase resins represent a new class of
      nucleolytic reagents and these systems have the potential to be further developed
      for multifarious applications in chemical biology.

PMID- 11288875
TI  - NaZn(H2O)2[BP2O8].H2O: a novel open-framework borophosphate and its reversible
      dehydration to microporous sodium zincoborophosphate N.
AB  - Crystals of NaZn(H2O)2[BP2O8].H2O were grown under mild hydrothermal conditions
      at 170 degrees C. The crystal structure (solved by X-ray single-crystal methods:
      hexagonal, P6(1)22 (no. 178), a = 946.2(2), c= 1583.5(1) pm, V= 1227.8(4).10(6)
      pm3, Z = 6) exhibits a chiral octahedral-tetrahedral framework related to the CZP
      topology and contains helical ribbons of corner-linked borate and phosphate
      tetrahedra. Investigation of the thermal behavior up to 180 degrees C shows a
      (reversible) dehydration process; this leads to the microporous compound
      Na[ZnBP2O8].H2O, which has the CZP topology. The crystal structure of
      Na[ZnBP2O8].H2O was determined by X-ray powder diffraction by using a combination
      of simulated annealing, lattice-energy minimization, and Rietveld refinement
      procedures (hexagonal, P6(1)22 (no. 178), a = 954.04(2), c = 1477.80(3) pm, V=
      164.88(5).10(6) pm3, Z = 6). The essential structural difference caused by the
      dehydration concerns the coordination of Zn2- changing from octahedral to
      tetrahedral arrangement.

PMID- 11288876
TI  - Molecular carpentry: piecing together helices and hairpins in designed peptides.
AB  - The design of a peptide that contains two distinct elements of secondary
      structure, helix and beta-hairpin, is described. Two designed 17-residue
      peptides: Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Gly-Gly-Leu-Phe-Val-D-Pro-Gly-Leu-Phe
      Val-OMe (I) and Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-Gly-Gly-Leu-Val-Val-D-Pro-Gly-Leu
      Val-Val-OMe (II) have been conformationally characterized by NMR spectroscopy.
      Peptides I and II contain a seven-residue helical module at the N terminus and a
      eight-residue beta-hairpin module at the C terminus, which are connected by a
      conformationally flexible Gly-Gly segment. The choice of the secondary-structure
      modules is based upon prior crystallographic and spectroscopic analysis of the
      individual modules. Analysis of 500 MHz 1H NMR data, recorded as solutions in
      methanol, suggests that the observed pattern of chemical shifts, 3JHN CalphaH
      values, temperature coefficients of the NH chemical shifts, and backbone inter
      residue nuclear Overhauser effects favor helical structures for residues 1-7 and
      beta-hairpin structures for residues 10-17. The spectroscopic data are compatible
      with termination of the helical segment by formation of a Schellman motif; this
      restricts Gly(8) to a left-handed alpha-helical conformation. Gly(9) is the only
      residue with multiple conformational possibilities in phi,psi space. Possible
      orientations of the two secondary-structure modules are considered. This study
      validates the use of stereochemically rigid peptide modules as prefabricated
      elements in the construction of synthetic protein mimics.

PMID- 11288879
TI  - Structural phase transitions in CaC2.
AB  - Pure CaC2, free of CaO impurities, was obtained by the reaction of elemental
      calcium with graphite at 1,070 K. By means of laboratory X-ray and synchrotron
      powder diffraction experiments, the phase diagram was investigated in the
      temperature range from 10 K to 823 K; this confirmed the literature data that
      reported the partial coexistence of up to four modifications. Aside from a cubic
      high-temperature modification CaC2 IV (Fm3m, Z = 4) and the well-known tetragonal
      modification CaC2 I (I4/mmm, Z = 2), a low-temperature modification CaC2 II
      (C2/c, Z =4) that crystallizes in the ThC2 structure type and a metastable
      modification CaC2 III (C2/m, Z = 4) that crystallizes in a new structure type
      were found. It was shown that phase transition temperatures as well as the
      relative amounts of the various CaC2 modifications depend upon the size of the
      crystallites, the thermal treatment. and the purity of the sample, as a
      comparison with technical CaC2 confirmed.

PMID- 11288878
TI  - Experimental proof for the structure of a thrombin-inhibiting heparin molecule.
AB  - Kinetic studies of thrombin inhibition by antithrombin in the presence of heparin
      have shown that thrombin binds to heparin in a preformed heparin-antithrombin
      complex. To study the relative position of the thrombin binding domain and the
      antithrombin binding domain on a heparin molecule we have designed and
      synthesized heparin mimetics, which structurally are very similar to the genuine
      polysaccharide. Their inhibitory properties with respect to factor Xa and
      thrombin provide experimental evidence that in heparin the thrombin binding
      domain must be located at the nonreducing end of the antithrombin binding domain
      to observe thrombin inhibition. As expected, factor Xa inhibition is not affected
      by elongation of the antithrombin binding pentasaccharide sequence, regardless of
      the position in which this elongation takes place.

PMID- 11288877
TI  - f-Element disiloxanediolates: novel Si-O-based inorganic heterocycles.
AB  - The preparation and structural characterization of scandium and f-element
      complexes derived from the disiloxanediolate dianion, [(Ph2SiO)2O]2-, are
      reported. Reactions of in situ prepared Ln[N(SiMe3)2]3 (Ln = Eu, Sm, Gd) with
      (Ph2SiOH)2O in different stoichiometries afforded the lanthanide
      disiloxanediolates [Eu[[(Ph2SiO)2O]Li(Et2O)]3] (1),
      [[[(Ph2SiO)2O]Li(dme)]2SmCl(dme)] (2), and [[[((Ph2SiO)2O]Li(thf)2]2GdN(SiMe3)2]
      (3). In situ formed (Ph2SiOLi)2O reacted with anhydrous NdBr3 (molar ratio 3:1)
      to give polymeric [[Nd[(Ph2SiO)2O]3[mu-Li(thf)]2[mu2LiBrLi(thf)(Et2O)]]n] (4).
      Treatment of 3 with Ph2Si(OH)2 in the presence of acetonitrile yielded the
      dilithium trisiloxanediolate derivative [[Ph2Si(OSiPh2O)2][Li(MeCN)]2]2 (5),
      which according to an X-ray analysis displays an Li4O4 heterocubane structure.
      The trinuclear scandium complex [[[(Ph2SiO)2O]Sc(acac)2]2Sc(acac)] (6) was
      obtained by reaction of [(C5Me5)Sc(acac)2] (C5Me5 = eta5
      pentamethylcyclopentadienyl) with (Ph2SiOH)2O in a 3:2 molar ratio. Selective
      formation of the colorless uranium(VI) derivative
      [U[Ph2Si(OSiPh20)2]2[(Ph2SiO)2O]] (7) was observed when uranocene, U(eta8-C8H8)2,
      was allowed to react with (Ph2SiOH)2O. An X-ray diffraction study of the solvated
      derivative [U[Ph2Si(OSiPh2O)2]2[(Ph2SiO)2O]].Et2O.TMEDA (TMEDA= N,N,N',N'
      tetramethyl-ethylenediamine) (7a) revealed the presence of both the original
      [(Ph2SiO)2O]2- dianion as well as the ring-enlarged [Ph2Si(OSiPh2O)2]2- ligand in
      the same molecule.

PMID- 11288880
TI  - Syntheses of halogenated ethenyl isocyanide chromium complexes as organometallic
      precursor molecules for ethenyl and ethynyl isocyanides.
AB  - The radical alkylation of tetraethylammonium pentacarbonyl(cyano)chromate 1
      yielded the halogenated ethyl isocyanide complexes [(CO)5Cr(CN-CClX-CClYF)] 3 (a,
      X= Cl, Y= F; b, X = F, Y= F and c, X=Y= Cl). Dehalogenation of 3 using zinc in
      diethyl ether gave [(CO)5Cr(CN-CX=CFY)] 4. The compounds 4a, b reacted with
      various nucleophiles exclusively at the difluoromethylene group. The unstable
      phosphorane 5, which is formed on reaction of 4b with trimethylphosphane,
      decomposed thermally and on hydrolysis yielding pentacarbonyl(1,2-difluoroethenyl
      isocyanide)chromium (6). The cyano substituent can be introduced in the beta
      position of the isocyanide function by reaction of 4a, b with potassium cyanide,
      leading to the formation of [(CO)5Cr(CN-CX=CF-CN)] (7). Reactions of 4a, b with
      organolithium or organomagnesium compounds yielded [(CO)5Cr(CN-CX=CF-R)] (8) and
      [(CO)5Cr(CN-CF=CF-C...C-CF=CF-NC)Cr(CO)5] (10). The trimethylsilyl group in 8a,
      b, d could be removed by a solution of potassium carbonate in methanol leading to
      [(CO)5Cr(CN-CX=CF-Cn-H)] (11) (n=2,4). Octacarbonyldicobalt reacted with 8e under
      coordination of the C-C triple bond to the hexacarbonyldicobalt fragment,
      resulting in the cluster compound 12. The crystal and molecular structure of 8i,
      11 a, b, and 12 were elucidated by X-ray crystallography. The alkenyl and alkynyl
      isocyanides CN-CCl=CF2 (13a), CN-CF=CF2 (13b), CN-CCl=CClF (13c), CN-CF=CFH (14),
      CN-CC-H (15), CN-CC-CN (16), and CN-CCl=CF-CN (17) were obtained by flash vacuum
      pyrolysis of 4a, 4b, 4c, 6, and 7a, respectively.

PMID- 11288881
TI  - Fluorescent and electroactive cyclic assemblies from perylene tetracarboxylic
      acid bisimide ligands and metal phosphane triflates.
AB  - Tetraaryloxy-substituted perylene tetracarboxylic acid bisimides with one or two
      4-pyridyl receptor substituents at the imide functionality were synthesized and
      employed in transition metal directed self-assembly with Pd(II) and Pt(II)
      phosphane triflates. Upon mixing of the components, quantitative formation of
      functional molecular square-type complexes containing four dye molecules and
      model complexes of a 2:1 (perylene bisimide ligand:transition metal ion)
      stoichiometry was observed. The isolated metallosupramolecular squares were
      characterized by 1H and 31P [1H] NMR spectroscopy as well as conventional
      electrospray ionization (ESI) and ESI-FTICR mass spectrometry, which gave
      evidence for the structure and the high stability of these giant cyclic dye
      assemblies (molecular weight (3a) 8172, Pt-Pt corner diagonal ca. 3.4 nm).
      Studies of the optical absorption and fluorescence properties and the
      electrochemistry and spectroelectrochemistry of both the perylene bisimide
      ligands and the perylene bisimide metal complexes show that Pt(II) coordination
      does not interfere with the optical and electrochemical properties of the
      perylene bisimide ligands; this gives squares with high fluorescence quantum
      yields (phiF (3a)=0.88) and three fully reversible redox couples. The latter
      could be unambiguously related to quantitative formation of perylene bisimide
      radical cations (E1/2 = +0.93 V vs. Fc/Fc+), radical anions (E1/2= - 1.01 V vs.
      Fc/Fc+), and dianions (E1/2 = -1.14 V vs. Fc/Fc+); these redox reactions change
      the charge state of the cyclic assembly from +12 to zero. In contrast, Pd(II)
      coordination influenced the electrochemical properties of the assembly because of
      an irreversible palladium reduction at E1/2= -1.15 V versus Fc/Fc+. Finally,
      dynamic ligand exchange processes between different metallosupramolecular
      assemblies were investigated by multinuclear NMR and electrospray mass
      spectrometry. These studies confirmed the reversible nature of the pyridine
      Pt(II)/Pd(II) coordination process.

PMID- 11288882
TI  - Reactions of difluoroenoxysilanes with glycosyl donors: synthesis of difluoro-C
      glycosides and difluoro-C-disaccharides.
AB  - Difluoroenoxysilanes, prepared from acylsilanes and
      trifluoromethyltrimethylsilane under fluoride activation, were glycosylated with
      some glycosyl donors (acylglycosides, glycals) to yield difluoro-C-glycosides
      with a difluoromethylene group in the place of the anomeric oxygen. This reaction
      strongly depends on the substituent in the 2-position of the glycosyl donor.
      Application of this methodology to a xylose-derived acylsilane led to the
      formation of difluoro-C-disaccharides as an isosteric O-glycosyl mimetic.

PMID- 11288883
TI  - Modification and inhibition of vancomycin group antibiotics by formaldehyde and
      acetaldehyde.
AB  - It is shown that several vancomycin group antibiotics (vancomycin, eremomycin,
      and avoparcin) undergo spontaneous chemical modifications when kept at room
      temperature at neutral pH in aqueous solutions containing traces of formaldehyde
      or acetaldehyde. This chemical modification predominantly results in a mass
      increase of 12 Da in the reaction with formaldehyde and 26 Da in the case of
      acetaldehyde. By using tandem mass spectrometry the modification can
      unambiguously be identified as originating from the formation of a ring-closed 4
      imidazolidinone moiety at the N-terminus of the glycopeptide antibiotics, that
      is, near the receptor binding pocket of the glycopeptide antibiotics. Bioaffinity
      mass spectrometry shows that this ring-closure results in a dramatically
      decreased affinity for the peptidoglycan-mimicking D-alanyl-D-alanine receptor.
      Additionally, in vitro inhibition measurements on two different strains of
      bacteria have revealed that the modified antibiotics display reduced
      antibacterial activity. The ring-closure is also shown to have a dissociative
      effect on the dimerization of the vancomycin-analogue eremomycin. The spontaneous
      reaction of vancomycin with formaldehyde or acetaldehyde may have implications
      not only for the clinical use of this class of antibiotics, but also for the
      effectiveness of these antibiotics when they are used in chiral separation
      chromatography or capillary electrophoresis.

PMID- 11288884
TI  - Complex formation of Ni(II), Cu(II), Pd(II), and Co(III) with 1,2,3,4
      tetraaminobutane.
AB  - Complex formation of the two tetraamine ligands (2S,3S)-1,2,3,4-tetraaminobutane
      (threo-tetraaminobutane, ttab) and (2R,3S)-1,2,3,4-tetraaminobutane (erythro
      tetraaminobutane, etab) with Co(III), Ni(II), Cu(II), and Pd(II) was investigated
      in aqueous solution and in the solid state. For Ni(II) and Cu(II), the pH
      dependent formation of a variety of species [Mn(II)xLyHz](2x+z)+ was established
      by potentiometric titrations and UV/Vis spectroscopy. In sufficiently acidic
      solutions the divalent cations formed a mononuclear complex with the doubly
      protonated ligand of composition [M(H2L)]4+. An example of such a complex was
      characterized in the crystal structure of [Pd(H2ttab)Cl2]Cl2.H2O. If the metal
      cation was present in excess, increase of pH resulted in the formation of
      dinuclear complexes [M2L]4+. Such a species was found in the crystal structure of
      [Cu2(ttab)Br4].H2O. Excess ligand, on the other hand, lead to the formation of a
      series of mononuclear bis-complexes [Mq(HxL)(HyL)](q+x+y)+. The crystal structure
      of [Co(Hetab)2][ZnCl4]2Cl. H2O with the inert, trivalent Co(III) center served as
      a model to illustrate the structural features of this class of complexes. By
      using an approximately equimolar ratio of the ligand and the metal cation, a
      variety of polymeric aggregates both in dilute aqueous solution and in the solid
      state were observed. The crystal structure of Cu2(ttab)3Br4, which exhibits a two
      dimensional, infinite network, and that of [Ni8(ttab)12]Br16.17.5H2O, which
      contains discrete chiral [Ni8(ttab)12]16+ cubes with approximate T symmetry, are
      representative examples of such polymers. The energy of different diastereomeric
      forms of such complexes with the two tetraamine ligands were analyzed by means of
      molecular mechanics calculations, and the implications of these calculations for
      the different structures are discussed.

PMID- 11288885
TI  - Nanofabrication: conventional and nonconventional methods.
AB  - Nanofabrication is playing an ever increasing role in science and technology on
      the nanometer scale and will soon allow us to build systems of the same
      complexity as found in nature. Conventional methods that emerged from
      microelectronics are now used for the fabrication of structures for integrated
      circuits, microelectro-mechanical systems, microoptics and microanalytical
      devices. Nonconventional or alternative approaches have changed the way we
      pattern very fine structures and have brought about a new appreciation of simple
      and low-cost techniques. We present an overview of some of these methods, paying
      particular attention to those which enable large-scale production of lithographic
      patterns. We preface the review with a brief primer on lithography and pattern
      transfer concepts. After reviewing the various patterning techniques, we discuss
      some recent application issues in the fields of microelectronics,
      optoelectronics, magnetism as well as in biology and biochemistry.

PMID- 11288886
TI  - Proteomics on a chip: promising developments.
AB  - The field of proteomics is expanding rapidly due to the completion of the human
      genome and the realization that genomic information is often insufficient to
      comprehend cellular mechanisms. This considerable expansion of proteomics towards
      high-throughput platforms is stressing its current technical capabilities. In
      recent years, technologies in microfluidic and array technologies have appeared
      for proteomics. These novel approaches might help solve current technical
      challenges in proteomics. This review presents a general survey of the recent
      development in microfluidic and array technologies from a proteomics perspective.

PMID- 11288887
TI  - Field-inversion electrophoresis on a microchip device.
AB  - We have proposed a field-inversion electrophoresis on a microchip for a shorter
      effective length, and investigated the external frequency for the DNA analysis
      based on the field-inversion electrophoresis device. By using the optimized
      frequency, we demonstrated that the field-inversion electrophoresis has great
      potentials for the separation of DNA fragments with shorter effective length.

PMID- 11288888
TI  - Shah convolution Fourier transform detection: multiple-sample injection
      technique.
AB  - For the direct measurement of electrophoretic mobility, multiple-point (Shah
      function) detected, time-domain detector signals were converted into frequency
      domain plots by means of Fourier transformation. Multiple sample plugs (up to a
      maximum of three) were introduced into the separation channel and the resultant
      time-domain signals were then Fourier-transformed. The multiple-sample injection
      technique has been successfully demonstrated for a one-component system and a
      separation. Though the number of fluorescing zones flowing through the
      illuminated length of the channel is greater than the number of analytes in the
      solution, Shah convolution Fourier transform detection (SCOFT) is able to
      identify the number of fluorescent species in the solution based on their
      migration velocities. The height of the fundamental peak increases as the number
      of injected sample plugs is increased. More importantly, the signal-to-noise
      ratio (S/N) is found to be proportional to the number of injected sample plugs.
      With these findings, the multiple-sample injection technique certainly has got
      many potential applications in trace analysis. The technique would be equally
      applicable to other separation techniques (e.g., high-performance liquid
      chromatography) and detection methods (e.g., absorption, refractive index).

PMID- 11288889
TI  - Fabrication of quartz microchips with optical slit and development of a linear
      imaging UV detector for microchip electrophoresis systems.
AB  - We have developed quartz microchips for electrophoresis and a linear imaging UV
      detector along with the microchip. The microchips have an optical slit, which cut
      off the stray light in order to improve the sensitivity of UV absorption
      detection on the chip, at the bonding interface. They have been successfully
      fabricated on synthesized quartz glass substrates using the hydrofluoric acid
      (HF) solution bonding method. The signal level of UV absorption detection was
      effectively improved by applying microchips with the "on-chip" optical slit. It
      is also possible to improve the signal-to-noise ratio by repetitive scanning of
      linear photodiode array located along the separation channel, and signal
      averaging during elimination of the potential. Furthermore, the analysis may be
      performed until the separation of the target component is complete, because the
      real-time migration pattern of each component in the sample can be seen just as
      in a slab-gel electrophoresis, thus enabling a shorter analysis time.

PMID- 11288890
TI  - New approaches for fabrication of microfluidic capillary electrophoresis devices
      with on-chip conductivity detection.
AB  - In practice, microfluidic systems are based on the principles of capillary
      electrophoresis (CE), for a large part due to the simplicity of electroosmotic
      pumping. In this contribution, a universal conductivity detector is presented
      that allows detection of charged species down to the microM level. Additionally,
      powderblasting is presented as a novel technique for direct etching of
      microfluidic networks. This method allows creation of features down to 50 microm
      with a total processing time (design to device) of less than one day. The
      performance of powderblasted devices with integrated conductivity detection is
      illustrated by the separation of lithium, sodium, and potassium ions and that of
      fumaric, malic, and citric acid.

PMID- 11288891
TI  - Fabrication and evaluation of a carbon-based dual-electrode detector for
      poly(dimethylsiloxane) electrophoresis chips.
AB  - The first carbon-based dual-electrode detector for microchip capillary
      electrophoresis (CE) is described. The poly(dimethylsiloxane) (PDMS)-based
      microchip CE devices were constructed by reversibly sealing a PDMS layer
      containing separation and injection channels to another PDMS layer containing
      carbon fiber working electrodes. End-channel amperometric detection was employed
      and the performance of the chip was evaluated using catechol. The response was
      found to be linear between 1 and 600 microM with an experimentally determined
      limit of detection (LOD) of 500 nM and a sensitivity of 30 pA/microM. Collection
      efficiencies for catechol ranged from 36.0 to 43.7% at field strengths of 260-615
      V/cm. The selectivity that can be gained with these devices is demonstrated by
      the first CE-based dual-electrode detection of a Cu(II) peptide complex. These
      devices illustrate the potential for a rugged and easily constructed microchip CE
      system with an integrated carbon-based detector of similar scale.

PMID- 11288892
TI  - Micromachined filter-chamber array with passive valves for biochemical assays on
      beads.
AB  - The filter-chamber array presented here enables a real-time parallel analysis of
      three different samples on beads in a volume of 3 nL, on a 1 cm2 chip. The filter
      chamber array is a system containing three filter-chambers, three passive valves
      at the inlet channels and a common outlet. The design enables parallel sample
      handling and time-controlled analysis. The device is microfabricated in silicon
      and sealed with a Pyrex lid to enable real-time analysis. Single nucleotide
      polymorphism analysis by using pyrosequencing has successfully been performed in
      single filter-chamber devices. The passive valves consist of plasma-deposited
      octafluorocyclobutane and show a much higher resistance towards water and surface
      active solutions than previous hydrophobic patches. The device is not sensitive
      to gas bubbles, clogging is rare and reversible, and the filter-chamber array is
      reusable. More complex (bio)chemical reactions on beads can be performed in the
      devices with passive valves than in the devices without valves.

PMID- 11288893
TI  - Sample preconcentration by field amplification stacking for microchip-based
      capillary electrophoresis.
AB  - A microchip structure for field amplification stacking (FAS) was developed, which
      allowed the formation of comparatively long, volumetrically defined sample plugs
      with a minimal electrophoretic bias. Up to 20-fold signal gains were achieved by
      injection and separation of 400 microm long plugs in a 7.5 cm long channel. We
      studied fluidic effects arising when solutions with mismatched ionic strengths
      are electrokinetically handled on microchips. In particular, the generation of
      pressure-driven Poiseuille flow effects in the capillary system due to different
      electroosmotic flow velocities in adjacent solution zones could clearly be
      observed by video imaging. The formation of a sample plug, stacking of the
      analyte and subsequent release into the separation column showed that careful
      control of electric fields in the side channels of the injection element is
      essential. To further improve the signal gain, a new chip layout was developed
      for full-column stacking with subsequent sample matrix removal by polarity
      switching. The design features a coupled-column structure with separate stacking
      and capillary electrophoresis (CE) channels, showing signal enhancements of up to
      65-fold for a 69 mm long stacking channel.

PMID- 11288894
TI  - Combined laser tweezers and dielectric field cage for the analysis of receptor
      ligand interactions on single cells.
AB  - A new technique based on the combination of optical and chip-based
      dielectrophoretical trapping was developed and employed to manipulate cells and
      beads with micrometer precision. The beads were trapped with optical tweezers
      (OT) and brought into contact for defined times with cells held in the
      dielectrophoretic field cage (DFC). The well-defined ligand-receptor system
      biotin-streptavidin was used to study the multiple interaction between
      biotinylated live cells and streptavidin-coated beads. The biotin density on the
      cell surface was varied down to a few single bonds (3 +/- 2 bonds/microm2) to
      control the valency of the binding. The quantitative relationship between the
      contact area, ligand density and its diffusion rate in the outer membrane of the
      cell could be demonstrated. The increase of the strength of the cell-bead
      adhesion was strictly dependent on the increase of individual bond numbers in the
      contact area. This is in part due to accumulation of ligands (D approxiamtely
      (0.5 +/- 0.1) 10(-8) cm2/s) in the contact area as seen by confocal laser
      scanning microscopy. Individual receptor-ligand rupture forces were evaluated and
      are compatible with values obtained by biomembrane force probe techniques. To
      summarize, the combination leads to a new powerful microsystem for cell handling
      and pN-force measurements on the single-cell level.

PMID- 11288895
TI  - High-speed separation system of randomly suspended single living cells by laser
      trap and dielectrophoresis.
AB  - We developed a new system for random separation of a single microorganism, such
      as a living cell and a microbe, in the microfluidic device under the microscope
      by integrating the laser-trapping force and dielectrophoretic (DEP) force. An
      arbitrarily selected single microbe could be isolated in a microchannel, despite
      the presence of a large number of microbes in solution. Once the target microbe
      is trapped at the focal point of the laser, we can easily realize exclusion of
      excess microbes around the target by controlling the electric field, while
      keeping the target trapped by the laser at the focal point. To realize an
      efficient separation system, we proposed a new separation cell and produced it by
      microfabrication. Flow speed in the microchannel is adjusted and balanced to
      realize high-speed and high-purity extraction of the target. Some preliminary
      experiments are conducted to show the effectiveness. The target is trapped by the
      laser, transported, and is taken out from the extraction port. Total separation
      time is less than 20 s. Our method is extremely useful in the pure cultivation of
      the cell and will be a promising method for biologists in screening useful
      microbes.

PMID- 11288896
TI  - Indirect micromanipulation of single molecules in water-in-oil emulsion.
AB  - Based on real-time observation and micromanipulation, analytical methods for
      single DNA molecules have been under development for some time. Precise
      manipulation, however, is still difficult because single molecules are too small
      for conventional techniques. We have developed a chemical reaction system that
      uses water droplets in oil as containers of materials. The water droplets can be
      manipulated by optical force. The manipulation of the water droplets permits the
      fusion of two selected droplets. This process corresponds to mixing of different
      samples. We designate this system as "w/o (water-in-oil emulsion) microreactor
      system", and each droplet can be thought of as a "microreactor". In this system,
      single molecules can be manipulated readily, as a molecule can be contained in a
      microm-sized microreactor. The microreactor utilizes extremely small quantities
      of samples, therefore, reactions are rapid, as diffusion times in the
      microreactor are very short. The manipulation technique of the microreactors
      based on optical force has been applied to induce fusion between microreactors
      loaded with DNA and YOYO, a fluorescent dye that binds to DNA. This fusion
      induced a rapid binding of YOYO.

PMID- 11288897
TI  - DNA analysis on electrophoretic microchips: effect of operational variables.
AB  - Applicability of modern microfabrication technology to electrophoresis microchips
      initiated a rapidly moving interdisciplinary field in analytical chemistry.
      Electric field mediated separations in microfabricated devices (electrophoresis
      microchips) are significantly faster than conventional gel electrophoresis,
      usually completed in seconds to minutes. Electrophoretic separation of DNA
      molecules on microfabricated devices proved to have the potential to improve the
      throughput of analysis by orders of magnitude. The flexibility of electrophoresis
      microchips allows the use of a plethora of separation matrices and conditions. In
      this paper, we report on electric field mediated separation of fluorescent
      intercalator-labeled dsDNA fragments in polyvinylpyrrolidone matrix-filled
      microchannel structures. The separations were detected in real time by a
      confocal, single-point laser-induced fluorescence/photomultiplier setup. Effects
      of the sieving matrix concentration (Ferguson plot), migration characteristics
      (reptation plot), separation temperature (Arrhenius plot), as well as applied
      electric field strength and intercalator concentration on the separation of DNA
      fragments are thoroughly discussed.

PMID- 11288898
TI  - Electrophoresis in microfabricated devices using photopolymerized polyacrylamide
      gels and electrode-defined sample injection.
AB  - Microfabrication techniques have become increasingly popular in the development
      of the next generation of DNA analysis systems. While significant progress has
      been reported by many researchers, complete microfabricated integrated DNA
      analysis devices are still in the earliest stages of development. Most
      miniaturized analysis systems have incorporated noncross-linked polymer solutions
      as the separation medium of choice and the operation of these systems
      necessitates the use of high electric fields and long separation lengths. In this
      paper, we present two techniques that may help alleviate this problem and
      accelerate the development of the so-called 'lab-on-a-chip' systems. We present
      the use of photodefinable polyacrylamide gels as a sieving medium for DNA
      electrophoresis. These gels offer the significant advantages of faster curing
      times, locally controlled gel interface, and simpler handling over chemically
      polymerized gels. We also introduce an electrode-defined sample compaction and
      injection technique. This technique helps achieve sample compaction without
      migration into the gel and offers significant control over the size and
      application of the sample plug. The use of these technologies for double-stranded
      DNA separations in microfabricated separation systems is demonstrated.

PMID- 11288899
TI  - Electrophoretic injection bias in a microchip valving scheme.
AB  - The pinched injection strategy, implemented on microfabricated fluidic devices
      (microchips), was investigated for an electrophoretic injection bias. Both the
      sample loading and dispensing steps were found to contribute to the injection
      bias whereby neutral species were injected preferentially to anionic species. In
      the sample loading step, neutral species filled a larger volume in the cross
      intersection than anionic species. Similarly, in the dispensing step, a larger
      volume of neutral analyte was injected than anionic analyte. Up to a 27%
      difference in injected volumes was observed. Fluorescently labeled amino acids
      were used as model analytes.

PMID- 11288900
TI  - Design of an interface to allow microfluidic electrophoresis chips to drink from
      the fire hose of the external environment.
AB  - An interface design is presented that facilitates automated sample introduction
      into an electrokinetic microchip, without perturbing the liquids within the
      microfluidic device. The design utilizes an interface flow channel with a volume
      flow resistance that is 0.54-4.1 x 10(6) times lower than the volume flow
      resistance of the electrokinetic fluid manifold used for mixing, reaction,
      separation, and analysis. A channel, 300 microm deep, 1 mm wide and 15-20 mm
      long, was etched in glass substrates to create the sample introduction channel
      (SIC) for a manifold of electrokinetic flow channels in the range of 10-13 microm
      depth and 36-275 microm width. Volume flow rates of up to 1 mL/min were pumped
      through the SIC without perturbing the solutions within the electrokinetic
      channel manifold. Calculations support this observation, suggesting a leakage
      flow to electroosmotic flow ratio of 0.1:1% in the electrokinetic channels,
      arising from 66-700 microL/min pressure-driven flow rates in the SIC. Peak
      heights for capillary electrophoresis separations in the electrokinetic flow
      manifold showed no dependence on whether the SIC pump was on or off. On-chip
      mixing, reaction and separation of anti-ovalbumin and ovalbumin could be
      performed with good quantitative results, independent of the SIC pump operation.
      Reproducibility of injection performance, estimated from peak height variations,
      ranged from 1.5-4%, depending upon the device design and the sample composition.

PMID- 11288901
TI  - Integration of gene amplification and capillary gel electrophoresis on a
      polydimethylsiloxane-glass hybrid microchip.
AB  - We report on the development of a hybrid polydimethylsiloxane (PDMS)-glass
      microchip for genetic analysis by functional integration of polymerase chain
      reaction (PCR) and capillary gel electrophoresis (CGE), and on related
      temperature control systems for PCR on a PDMS-glass hybrid microchip. The
      microchip was produced by molding PDMS against a microfabricated master with
      comparatively simple and inexpensive methods. PCR was successfully carried out on
      the PDMS-glass hybrid microchip with 500 bp target of lambdaDNA and the amplified
      gene was subsequently analyzed by CGE on the same PDMS-glass microchip. The chip
      could be considered as an inexpensive single-use apparatus compared to glass or
      silicon-made microchips for the same purpose.

PMID- 11288902
TI  - Towards dynamic coating of glass microchip chambers for amplifying DNA via the
      polymerase chain reaction.
AB  - As microchip technology evolves to allow for the integration of more complex
      processes, particularly the polymerase chain reaction (PCR), it will become
      necessary to define simple approaches for minimizing the effects of surfaces on
      the chemistry/processes to be performed. We have explored alternatives to
      silanization of the glass surface with the use of additives that either
      dynamically coat or adsorb to the glass surface. Polyethylene glycol,
      polyvinylpyrrolidone (PVP), and hydroxyethylcellulose (HEC) have been explored as
      potential dynamic coatings and epoxy (poly)dimethylacrylamide (EPDMA) evaluated
      as an adsorbed coating. By carrying out analysis of the PCR products generated
      under different conditions via microchip electrophoresis, we demonstrate that
      these coating agents adequately passivate the glass surface in a manner that
      prevents interference with the subsequent PCR process. While several of the
      agents tested allowed for PCR amplification of DNA in glass, the EPDMA was
      clearly superior with respect to ease of preparation. However, more efficient PCR
      (larger mass of amplified product) could be obtained by silanizing the glass
      surface.

PMID- 11288903
TI  - Electroosmosis injection of blood serum into biocompatible microcapillary chip
      fabricated on quartz plate.
AB  - A chip which allows the detection of various human health markers from a trace
      amount of blood has been studied. As a goal, a microcapillary with a 30 x 30
      microm cross-section was fabricated using all-dry etching technologies on a 2 x 2
      cm SiO2 chip. The coating of the biocompatible 2
      methacryloyloxyethylphosphorylcholine (MPC) polymer on the inner quartz wall of
      the microcapillary demonstrated a sufficiently long adsorption suppression of
      proteins in the serum on the quartz surface, while rapid stopping occurred for
      serum injected into the microcapillary with a bare quartz surface. The latter
      rapid stopping corresponded well to fast electroosmosis flow due to the
      negatively increasing zeta-potential by the adsorption of proteins on the quartz
      surface. The electroosmosis pump arranged a downstream of the microcapillary was
      also developed to inject serum into it. As a preliminary application, a given
      concentration-standard solution was injected into the ion-sensitive field-effect
      transistor (ISFET) embedded in the chip, employing the electroosmosis pump
      arranged downstream of the sensor position. Hence, the pH and Na+ and K+ cation
      concentrations were measured.

PMID- 11288904
TI  - A capillary electrophoresis chip for the analysis of print and film photographic
      developing agents in commercial processing solutions using indirect fluorescence
      detection.
AB  - The separation and detection of both print and film developing agents (CD-3 and
      CD-4) in photographic processing solutions using chip-based capillary
      electrophoresis is presented. For simultaneous detection of both analytes under
      identical experimental conditions a buffer pH of 11.9 is used to partially ionise
      the analytes. Detection is made possible by indirect fluorescence, where the ions
      of the analytes displace the anionic fluorescing buffer ion to create negative
      peaks. Under optimal conditions, both analytes can be analyzed within 30 s. The
      limits of detection for CD-3 and CD-4 are 0.17 mM and 0.39 mM, respectively. The
      applicability of the method for the analysis of seasoned photographic processing
      developer solutions is also examined.

PMID- 11288905
TI  - Continuous concentration of bacteria in a microfluidic flow cell using
      electrokinetic techniques.
AB  - A novel method for the concentration of bacterial solutions is presented that
      implements electrokinetic techniques, zone electrophoresis (ZE) and isoelectric
      focusing (IEF), in a microfluidic device. The method requires low power (< 3e-5
      W) and can be performed continuously on a flowing stream. The device consists of
      two palladium electrodes held in a flow cell constructed from layers of polymeric
      film held together by a pressure-sensitive adhesive. Both ZE and IEF are
      performed with carrier-free solutions in devices in which the electrodes are in
      intimate contact with the sample fluid. IEF experiments were performed using
      natural pH gradients; no carrier ampholyte solution was required. Experiments
      performed in buffer alone resulted in significant electroosmotic flow.
      Pretreatment of the sample chamber with bleach followed by a concentrated
      solution of cationic detergent effectively suppressed electroosmotic flow.

PMID- 11288906
TI  - DNA separations in microfabricated devices with automated capillary sample
      introduction.
AB  - A novel method is presented for automated injection of DNA samples into
      microfabricated separation devices via capillary electrophoresis. A single
      capillary is used to electrokinetically inject discrete plugs of DNA into an
      array of separation lanes on a glass chip. A computer-controlled micromanipulator
      is used to automate this injection process and to repeat injections into five
      parallel lanes several times over the course of the experiment. After separation,
      labeled DNA samples are detected by laser-induced fluorescence. Five serial
      separations of 6-carboxyfluorescein (FAM)-labeled oligonucleotides in five
      parallel lanes are shown, resulting in the analysis of 25 samples in 25 min. It
      is estimated that approximately 550 separations of these same oligonucleotides
      could be performed in one hour by increasing the number of lanes to 37 and
      optimizing the rate of the manipulator movement. Capillary sample introduction
      into chips allows parallel separations to be continuously performed in serial,
      yielding high throughput and minimal need for operator intervention.

PMID- 11288907
TI  - Absence of adverse effects of sodium metabisulphite in manufactured biscuits:
      results of subacute (28-days) and subchronic (85-days) feeding studies in rats.
AB  - Sulphites are extensively used in the food and drinks industry. Their toxicity
      has been previously evaluated by addition to the diet or drinking water of
      laboratory animals. Because interactions between sulphites and food constituents
      occur, the present work was conducted to determine the subacute and subchronic
      toxicity of sulphite-bound compounds in a finished product: manufactured
      biscuits. The studies were performed on Sprague Dawley, rats for 28 and 85 days
      of dietary exposure. Diets were prepared from sulphited or untreated (controls)
      biscuits with the addition of sugar, protein, vitamins and minerals according to
      the nutritional requirements of the animals. Groups of 10 male and 10 female rats
      were administered diets containing sulphited biscuits at levels of 0, 10, 35 and
      75%, corresponding to 10-15, 35-45, 150-170 and 310-340 mg SO2/kg diet. In both
      studies, no death or clinical abnormalities were reported. Growth rate, food
      consumption and food conversion efficiency were not affected by treatment. No
      dose-related changes were observed for haematology, clinical chemistry, ocular
      examination, renal-function, urinalysis, organ weights or gross and microscopic
      examinations. The liver concentrations of vitamins A, B1, C and E were not
      significantly changed except for an increase in vitamin E in high-dose males
      after 28 days' exposure. Based on these data, the no-observed-adverse-effect
      level (NOAEL) of sulphites in baked biscuits was judged to be 310 mg SO2/kg diet
      or 25 mg/kg body weight/day.

PMID- 11288908
TI  - Daily intake of trace metals through coffee consumption in India.
AB  - The trace element contents of five varieties of instant coffee powder available
      in the Indian market have been analysed. Ca, Cr, Fe, K, Mg, Mn, Ni, Sr, Zn and
      Pb, Cd, Cu have been determined using atomic absorption spectrophotometry and
      differential pulse anodic stripping voltammetry, respectively. The metal levels
      in the coffee powders observed in this study are comparable with those reported
      for green coffe beans (Arabica and Robusta variety) reported worldwide with the
      exception of Sr and Zn, which were on the lower side of the reported values.
      Concentrations of these metals have been converted into intake figures based on
      coffee consumption. The daily intakes of the above metals through ingestion of
      coffee are 1.4 mg, 1.58 microg, 124 microg, 41.5 mg, 4.9 mg, 17.9 microg, 2.9
      microg, 3.8 microg, 12.5 microg, 0.2 microg, 0.03 microg and 15.5 microg,
      respectively. The values, which were compared with the total dietary, intake of
      metals through ingestion by the Mumbai population, indicate that the contribution
      from coffee is less than or around 1% for most of the elements except for Cr and
      Ni which are around 3%.

PMID- 11288909
TI  - Use of an immunoassay as a means to detect polychlorinated biphenyls in animal
      fat.
AB  - In this paper we describe the validation and utilization of the Hybrinzme DELFIA
      immunoassay for detecting polychlorinated biphenyls (PCBs) in animal fat. The
      immunoassay incorporates a rapid sample processing protocol that has been
      optimized to detect concentrations of PCBs in animal fat at or above 200 ng/g.
      The limit of detection of the assay was less than 50 ng/g. When the action level
      for the DELFIA assay was set at 100 ng/g to detect samples having 200 ng/g or
      more PCBs, the false negative rate was estimated at 0.2%. The false positive rate
      depends on the concentration of PCBs in the sample population and was estimated
      at 4% and 7% for samples having 10 ng/g and 20 ng/g PCBs, respectively. By
      utilizing the DELFIA assay system to select for positive samples and GC/MS
      analysis for confirmation analysis, an accurate and cost-effective programme has
      been established for the high throughput detection of PCBs in animal products.

PMID- 11288910
TI  - A survey of ethnic foods for microbial quality and aflatoxin content.
AB  - A range of ethnic foods was examined for their microbiological content in
      relation to total viable counts (TVC) of aerobic bacteria, counts of presumptive
      coliforms, yeast and mould counts; presence of Salmonella spp., Listeria
      monocytogenes, Escherichia coli O157:H7 and Campylobacter spp.; total enumeration
      of Clostridium perfringens, Staphylococcus aureus and Bacillus spp.;
      identification of moulds and the presence of total aflatoxins. Samples, which
      included cereals, nuts, dried fruits, herbs and spices, were obtained from local
      retail outlets and distributors. It was established that three samples of
      pistachio nuts contained significant levels of aflatoxins. The concentration of
      total aflatoxins in these three nut samples ranged from 15 to 259 microg/kg of
      sample. Only two other samples contained trace amounts of aflatoxins, all other
      samples analysed were found to be free of any detectable level of aflatoxins.
      TVCs, coliform counts and yeast and mould counts varied widely depending on the
      matrix tested. Generally, rice, wheat and peanuts produced low counts whereas
      other nuts, gram flour and spices produced much higher counts. Cl. perfringens,
      Staph. aureus, and Bacillus spp. were common in spices, nuts and gram flour,
      however, Listeria monocytogenes was only detected in four samples and in no
      sample could Salmonella spp, E. coli O157:H7 or Campylobacter spp. be detected.

PMID- 11288911
TI  - Differences detected in vivo between samples of aflatoxin-contaminated peanut
      meal, following decontamination by two ammonia-based processes.
AB  - A sample of peanut meal, highly contaminated with aflatoxins, has been subjected
      to decontamination by two commercial ammonia-based processes. The original
      contaminated and the two decontaminated meals were fed to rats for 90 days. No
      lesions associated with aflatoxin-induced hepatocarcinogenesis were detected
      histologically following feeding with the two detoxified meals. There were,
      however, clear differences between the two meals in respect of growth rates of
      the rats. In addition, feeding one of the detoxified meals resulted in hepatic
      abnormalities detected using novel immunohistochemical reagents. Differences
      between the two detoxified meals were also indicated by the results of studies
      using meals 'spiked' with [14C]-aflatoxin B1 prior to being subjected to the
      detoxification processes. The meals differed in the bioavailability of the label.
      It was concluded that peanut meal where an initial, unacceptable level of
      contamination with aflatoxins had been reduced by two ammonia-based processes to
      comparable, acceptable levels, may still have different effects in vivo when
      incorporated into animal diets.

PMID- 11288912
TI  - Natural occurrence of aflatoxins in Korean meju.
AB  - Aflatoxin B1 (AFB1) was found in 35 of 60 (58.3%) meju samples with an average
      concentration of 7.3 ng/g by ELISA. Contamination of AFB1 was confirmed in 25 of
      60 samples (41.6%) using HPLC, with an average concentration of 6.9 ng/g. Mean
      recoveries from meju ranged from 107% to 170% for AFB1 using ELISA at a spiking
      range of 1 to 50 ng/g. Over the same range, recoveries using HPLC were from 70%
      to 83%. The levels of AFB1 determined by ELISA and by HPLC demonstrated a close
      relationship between the two methods (r2 = 0.9324) employed in this study. In
      order to evaluate the potential health risks of AFB1 on Koreans consuming meju,
      we calculated the estimated probable daily intake (PDI) based on the average
      contamination levels and compared it with the estimated tolerable daily intake
      (TDI). The PDIs of AFB1 from kanjang and dwenjang were determined to be 0.04 and
      0.21 ng/kg bw/day, respectively, and were higher than TDIs.

PMID- 11288913
TI  - Migration of 4-nonylphenol from polyvinyl chloride food packaging films into food
      simulants and foods.
AB  - Migration of 4-nonylphenol (NP) from polyvinyl chloride (PVC) films for food
      packaging into food simulants and foods has been studied in domestic applications
      such as wrapping of food and reheating in a microwave oven. The migration of NP
      from the PVC films was determined by high-performance liquid chromatography with
      electrochemical coulometric-array detection (LC/ED). Twelve PVC films intended
      for commercial use and ten for domestic applications (total: 22 samples) were
      analysed. Some of the PVC films (two home-use and ten retail-use) contained NP at
      concentrations of between 500 and 3300 microg/g. Migration of NP from the films
      was influenced by the test conditions (n-heptane at 25 degrees C for 60 min,
      distilled water at 60 degrees C for 30 min and 4% acetic acid at 60 degrees C for
      30 min). The amount of NP migrating from the PVC films into n-heptane (0.33-1.6
      microg/cm2) was higher than the amount migrating into distilled water or 4%
      acetic acid (up to 9.7 ng/cm2) for the 11 films in which NP was detected. Up to
      0.23% of the NP migrated into distilled water and 4% acetic acid and up to 62.5%
      into n-heptane. In addition, we investigated NP migration into cooked rice
      samples wrapped in PVC film. Using spiked samples the method gave an average
      recovery of 83.7% (n = 5) with a standard deviation of 2.5%. Migration of NP
      ranged from not detectable (< 1.0 ng/g) to 410.0 ng/g by reheating samples in a
      microwave oven for 1 min and from not detectable to 76.5 ng/g by keeping samples
      at room temperature for 30 min.

PMID- 11288914
TI  - Tailoring fatty food simulants made from solvent mixtures (1): comparison of
      methanol, ethanol and isopropanol behaviour with polystyrene.
AB  - To investigate the use of solvent mixtures as test media replacing olive oil in
      migration tests, the interaction of polystyrene with mixtures composed of various
      amounts of tert.butyl acetate (mimicking the ester functions of oil) and of a low
      molecular weight alcohol (methanol, ethanol and isopropanol as inert co-solvent)
      was studied, using FTIR. Isopropanol, which has a lesser tendency to form
      hydrogen bonds in the plastic, can be used as main component of alternative fatty
      test media, its aggressiveness to polystyrene being tailored by adjusting the
      concentration of tert.butyl acetate. Concentrations below 20% seem useful on the
      basis of the mechanism of displacement of the alcohols.

PMID- 11288915
TI  - Chlorohydrins of bisphenol A diglycidyl ether (BADGE) and of bisphenol F
      diglycidyl ether (BFDGE) in canned foods and ready-to-drink coffees from the
      Japanese market.
AB  - BADGE.2HCl and BFDGE.2HCl were determined in 28 samples of ready-to-drink canned
      coffee and 18 samples of canned vegetables (10 corn, 5 tomatoes and 3 others),
      all from the Japanese market. HPLC was used as the principal analytical method
      and GC-MS for confirmation of relevant LC fractions. BADGE.2HCl was found to be
      present in one canned coffee and five samples of corn, BFDGE.2HCl in four samples
      of canned tomatoes and in one canned corn. No sample was found which exceeded the
      1 mg/kg limit of the EU for the BADGE chlorohydrins. However the highest
      concentration was found for the sum of BFDGE.2HCl anti BFDGE.HCl.H2O at a level
      of 1.5 mg/kg. A Beilstein test confirmed that all cans containing foods
      contaminated with BADGE.2HCl or BFDGE.2HCl had at lest one part coated with a PVC
      organosol.

PMID- 11288916
TI  - Outcome studies using immune-enhancing diets: blunt and penetrating torso trauma
      patients.

PMID- 11288917
TI  - Effect of immune enhancing formulas (IEF) in general surgery patients.

PMID- 11288918
TI  - Use of immune-enhancing diets in burns.

PMID- 11288919
TI  - The use of immune enhancing diet in head injury.

PMID- 11288920
TI  - Immune-enhancing diets: products, components, and their rationales.

PMID- 11288921
TI  - Immunonutrition in a multidisciplinary ICU population: a review of the
      literature.

PMID- 11288922
TI  - Effects of immune-enhancing diets on infectious morbidity and multiple organ
      failure.

PMID- 11288923
TI  - The effects of immune-enhancing diets (IEDs) on mortality, hospital length of
      stay, duration of mechanical ventilation, and other parameters.

PMID- 11288924
TI  - Immunonutrition in the critically ill patient: more harm than good?

PMID- 11288925
TI  - Discrepancies between nutrition outcome studies: is patient care the issue?

PMID- 11288926
TI  - Consensus recommendations from the US summitt on immune-enhancing enteral
      therapy.

PMID- 11288927
TI  - Enteral access--the foundation of feeding.

PMID- 11288928
TI  - Effect of glutathione (GSH) depletion on the serum levels of triiodothyronine
      (T3), thyroxine (T4), and T3/T4 ratio in allyl alcohol-treated male rats and
      possible protection with zinc.
AB  - The current study is an attempt to elucidate the link between glutathione (GSH)
      as a major endogenous antioxidant and the thyroid hormone levels. Rats were
      treated with a single intraperitoneal (IP) dose of either ZnCl2 (5 mg/kg) or
      allyl alcohol (AIAI) (1.5 mmol/kg), which acts as a GSH-depleting agent. ZnCl2
      and AIAI were administered either alone (Zn- and AlAl-treated groups) or in
      combination (AIAI + Zn-treated group). Blood and liver samples were collected 5
      hours post treatment in all groups. Zinc was used because of its potential
      intracellular regulatory effect as a calcium antagonist. The data indicate a
      decrease in the serum levels of triiodothyronine (T3) and thyroxin (T4), the
      T3/T4 ratio, and serum and liver total protein in AlAl-treated rats. Increases in
      the serum levels of aminotransferases, hepatic calcium, and lipid peroxidation
      products were observed. The decrease in T3 and the T3/T4 ratio indicates a
      reduced capacity of the microsomes to convert T4 into T3. Rats treated with AlAl
      + Zn had replenished hepatic GSH and showed a marked decrease in the serum levels
      of aminotransferases and in the liver calcium contents and lipid peroxidation
      products compared to AlAl-treated rats. In contrast, zinc treatment failed to
      normalize the serum levels of total protein, T3 and T4, and the T3/T4 ratio in
      the same rats. Rat treated with ZnCI2 alone tended to have a lower serum protein
      level that was accompanied with a significant decrease in both serum T3 and the
      T3/T4 ratio. The effect of zinc in increasing capillary permeability with the
      probable leakage of some serum proteins including the thyroid-binding proteins
      could possibly be the reason behind this finding. Possible covalent binding of
      AIAI metabolites to some cellular proteins may explain the persistence of reduced
      liver protein levels in zinc-protected rats.

PMID- 11288929
TI  - Role of protein phosphorylation in the inhibition of protein synthesis caused by
      hypoxia in rat hepatocytes.
AB  - Hypoxia causes a rapid and reversible inhibition of translation in freshly
      isolated rat hepatocytes. This inhibition is neither due to an ATP loss nor to an
      increase in cell death. Because protein synthesis is mainly regulated by
      reversible phosphorylation of initiation and/or elongation factors, we
      investigated whether translation inhibition by hypoxia may be related to changes
      in the phosphorylation status of proteins. Whatever the incubation conditions,
      three phosphoreactive bands (molecular weights 220, 129, and 83 kDa) were
      detected by antiphosphotyrosine antibodies. The phosphorylation in the 129- and
      83-kDa bands, however, was significantly and progressively decreased under
      hypoxia. Although this time-dependent decrease was sensitive to changes in oxygen
      tension, it occurred after the early protein synthesis inhibition caused by
      hypoxia. Moreover, sodium orthovanadate prevented tyrosine dephosphorylation in
      hypoxic cells, but did not restore the depressed protein synthesis caused by
      hypoxia. Under aerobic conditions, orthovanadate inhibited the synthesis of
      proteins, confirming that protein phosphorylation is a major mechanism involved
      in translational regulation. Once again, this inhibitory effect occurred only
      after 90 minutes of incubation whereas hypoxia inhibits the protein synthesis at
      the beginning of the incubation. Labeling cells with [33-32P]-ortho-phosphoric
      acid allowed detection of several phosphorylated proteins that appeared under
      hypoxia. Because they were not recognized by the phosphotyrosine antibodies, we
      suggest that serine/threonine residues of key proteins may be the putative
      hypoxic targets.

PMID- 11288930
TI  - Reproductive toxicity of MCPA (4-chloro-2-methylphenoxyacetic acid) in the rat.
AB  - The reproductive effects of the administration of 4-chloro-2-methylphenoxyacetic
      acid (MCPA) to rats were evaluated through two generations, from prior to mating,
      throughout mating, to gestation and lactation. MCPA was administered in the diet
      at doses of 0, 50, 150, or 450 ppm to 25 male and female immature rats (F0
      parents) for 10 weeks. F0 parents were then mated to produce a first litter
      (F1a), retained only until weaning, and were subsequently remated to produce a
      second litter, F1b. Groups of male and female F1b animals were then dosed as were
      their parents for 10 weeks postweaning, and the breeding was repeated to produce
      F2a and F2b animals. The study concluded with the F2b weanlings. MCPA was
      administered continuously throughout the study. Only minimal, non-treatment
      related observations were noted, which included rhinorrhea (in both treated and
      control animals in the F0 generation) and malocclusion and alopecia (in both the
      F0 and F1b generations). There were no consistent dose-related effects on
      reproductive function for parental animals of either sex in either generation.
      Statistically significant differences were noted in body weights and body weight
      gains in the 450-ppm dose group for both male and female pups in F2a and F2b.
      There were no treatment-related macroscopic or microscopic observations noted for
      any animal in this study. The no-observable-effect level (NOEL) for reproductive
      function in rats administered MCPA continuously for two successive generations
      was determined to be 450 ppm (approximately 22 mg/kg/day). The NOEL for general
      systemic toxicity, based on body weight effects in adult animals in the F1b
      generation was 150 ppm. The NOEL for effects on the offspring of the F1b
      generation, manifested as reduced pup weights and pup weight gains was also 150
      ppm (approximately 8 mg/kg/day). Based upon the results of this study, MCPA,
      administered for two generations to Crl:CD(SD)BR Albino rats, is considered not
      to be a reproductive toxicant.

PMID- 11288931
TI  - Toxicology at the Food and Drug Administration: new century, new challenges.
AB  - Dr. Schwetz is the Acting Deputy Commissioner of the Food and Drug Administration
      (FDA). He was Director of FDA National Center for Toxicological Research in
      Jefferson, AR, from 1993 to 1999. A diplomate of the American Board of
      Toxicology, Dr. Schwetz was acting Director of the Environmental Toxicology
      Program at the National Institutes of Health National Institute of Environmental
      Health Sciences (NIEHS) in Research Triangle Park, NC, before coming to the FDA
      in 1993. He was also Associate Director of the National Toxicology program there.
      He had been Chief of the Institute Systems Toxicity Branch since 1982. Dr.
      Schwetz currently serves as Adjunct Professor, Department of Pharmacology and
      Toxicology/Division of Interdisciplinary Toxicology, at the University of
      Arkansas for Medical Sciences. He was editor of Fundamental and Applied
      Toxicology from 1986 to 1992, and serves on the Editorial Advisory Board of
      Environmental Health Perspectives and Critical Reviews in Toxicology. Dr. Schwetz
      is an invited member of the Canada Health Protection Branch Science Advisory
      Board, and an elected member of the National Academy of Sciences Institute of
      Medicine. He is a member of the Society of Toxicology (SOT) and the National
      Capitol Area Chapter, SOT; the American Veterinary Medical Association; National
      Society of Phi Zeta, Honor Society of Veterinary Medicine; Teratology Society;
      Behavioral Teratology Society; and the Reproductive Toxicology Specialty Section
      of the SOT. He is past president of the Reproductive Toxicology Specialty Section
      of the SOT and of the North Carolina and the South Central Chapters of the SOT.
      In addition to numerous other professional awards during his career, Dr. Schwetz
      received the U.S. Government 1998 Meritorious Executive Presidential Rank Award.

PMID- 11288932
TI  - Effect of maitotoxin on guanine nucleotide interaction with G-protein alpha
      subunits.
AB  - Maitotoxin is a potent water-soluble polyether toxin produced by the marine
      dinofiagellate Gambierdiscus toxicus. Although associated with increased calcium
      uptake, mobilization of internal calcium stores, and enhanced phosphoinositide
      metabolism, the primary molecular mechanism underlying its actions remains
      unclear. In this study, we evaluated the effects of maitotoxin (MTX) on the
      interaction of guanine nucleotides with G-protein alpha subunits. Equilibrium
      binding of the nonhydrolyzable GTP analog, GTPgammaS, to alpha subunits (Go, Gs,
      Gi1, Gi2, and Gi3) was decreased in the presence of MTX. Furthermore,
      reconstitution of Galpha with Gbetagamma dimer showed a reversal of the
      inhibition elicited by MTX. GDP/GTP exchange rate for Galpha subunits was
      significantly inhibited in the presence of MTX. MTX had no effect on the rate of
      GDP or GTP dissociation from alpha subunits. Also, the mastoparan-induced
      component of nucleotide exchange is not effected by MTX. These results suggest
      that MTX acts on Galpha subunits to modulate their interaction with guanine
      nucleotides, perhaps by stabilizing an empty state of the alpha subunit.
      Accordingly, MTX may disrupt the normal signal transduction pathways by
      inhibiting GTP binding to Galpha subunits and interfering with the GDP/GTP
      exchange.

PMID- 11288934
TI  - The future of biotechnology testing in the next decade: a perspective.
AB  - The power of genomics in transforming the biotechnology industry will be evident
      in all areas of drug discovery and development. This will be particularly true in
      safety evaluation, where the field will be forced to adapt to new schemes of e
      R&D and e-business in general. Toxicologists will be required to create
      information-rich, real-time systems that can be used for decisions in the
      earliest phases of discovery and throughout development. The largest growth area
      in specific product types will be those that can move genomics information from
      the laboratory to the clinic the fastest.

PMID- 11288933
TI  - Two-week (ten-day) inhalation toxicity and two-week recovery study of phenol
      vapor in the rat.
AB  - The toxicity of phenol vapor was evaluated in male and female Fischer 344 rats
      (20/sex/group) via flow-past nose-only inhalation exposure. The test animals were
      exposed to target concentrations of 0 (air control), 0.5, 5.0, or 25 parts per
      million (ppm) of phenol in air for 6 hours/day, 5 days/week, for 2 weeks. High
      pressure liquid chromatography (HPLC) measurement of phenol test atmospheres
      determined mean (+/- standard deviation) analytical concentrations of 0.0 +/-
      0.0, 0.52 +/- 0.078, 4.9 +/- 0.57, and 25 +/- 2.2 ppm, respectively. After 2
      weeks of exposure, 10 test animals/sex/group were sampled for clinical chemistry
      and hematology parameters, and then sacrificed. Histopathological examination
      included the nasopharyngeal tissues, larynx, trachea, lungs with mainstem
      bronchi, kidney, liver, and spleen. The remaining 10 animals/sex/group were
      retained for a 2-week recovery period. Recovery groups of animals were evaluated
      as described previously and then sacrificed. No signs of toxicity in clinical
      observations (including overt neurological signs), body weights, food
      consumption, clinical pathology, organ weights, macroscopic pathology or
      microscopic pathology were seen during the exposures or at either sacrifice
      interval. In conclusion, 2-week inhalation exposures to phenol vapor at
      concentrations up to and including 25 ppm did not produce any adverse effects.

PMID- 11288935
TI  - Obsessive relational intrusion: incidence, perceived severity, and coping.
AB  - Two studies investigated the phenomenon of obsessive relational intrusion (ORI),
      defined as repeated and unwanted pursuit and invasion of one's sense of physical
      or symbolic privacy by another person, either stranger or acquaintance, who
      desires and/or presumes an intimate relationship. In Study 1, we sought to
      identify the incidence of a broad range of relationally intrusive behaviors, to
      identify the coping responses employed by victims of ORI, and to assess the
      associations between coping responses and ORI behaviors. Study 2 assessed the
      perceived degree of severity of ORI behaviors. Results revealed that each of 63
      ORI behaviors was experienced by 3-78% of respondents in three different samples.
      Factor analysis revealed four types of ORI behavior: pursuit, violation, threat,
      and hyper-intimacy. Responses for coping with ORI consisted of interaction,
      protection, retaliation, and evasion. Virtually all intrusive behaviors were
      perceived to be annoying. Some types of ORI behaviors were perceived to be
      relatively more threatening, upsetting and privacy-invading than others. Although
      sex differences were not observed for the incidence of ORI or coping, women
      consistently perceived ORI behaviors to be more annoying, upsetting, threatening,
      and privacy-invading than did men.

PMID- 11288936
TI  - An integrative contextual developmental model of male stalking.
AB  - This article evaluates current research and theory on stalking as a form of male
      violence against women. The integrative contextual developmental model (White &
      Kowalski, 1998) suggests that stalking, as legally defined, is best understood as
      a multiply determined form of violence, with variables identifiable at several
      levels, the sociocultural, interpersonal, dyadic, situational and intrapersonal.
      The model also serves as a framework for identifying gaps in current research and
      suggests directions for further work.

PMID- 11288937
TI  - An empirical study of stalking victimization.
AB  - This article empirically studies the phenomenon of stalking and its victims by
      utilizing a random sample of college students at a large public University. The
      study found that 25% of the women and 11% of the men had been stalked at some
      point in their lives and that six percent were currently being stalked.
      Additionally, the study found that the majority of stalking victims are women who
      are stalked by male offenders. The sample reported being stalked for an average
      of 347 days and having engaged in a variety of actions in response. A substantial
      number of victims reported being threatened by their stalkers. This threat was
      associated with higher levels of fear among the victims and a greater chance of
      physical attack by the stalkers, particularly for the female victims.

PMID- 11288938
TI  - Stalking perpetrators and psychological maltreatment of partners: anger-jealousy,
      attachment insecurity, need for control, and break-up context.
AB  - Two studies of the correlates of self-reported courtship persistence, stalking
      like behaviors following a relationship break-up, and psychological maltreatment
      of partners were conducted in samples of male (N = 46 and 93) and female (N = 123
      and 110) college students. Approximately 40% (38.5% and 44.6%) engaged in at
      least one stalking behavior following a break-up. A total of 10.7% (study 1) and
      7.6% (study 2) engaged in 6 or more stalking behaviors. Stalking was
      significantly related to psychological maltreatment of the partner (PMP) prior to
      the break-up. Being the recipient of the breakup was associated with feelings of
      anger, jealousy and obsessiveness and with higher levels of courtship
      persistence, and stalking. A replicated path model showed that anxious attachment
      and need for control were related to PMP and that need for control had a direct
      contribution to stalking. For anxious attachment, its connection to stalking was
      indirect, mediated by the degree of anger-jealousy over the break-up.

PMID- 11288939
TI  - The role of stalking in domestic violence crime reports generated by the Colorado
      Springs Police Department.
AB  - A review of 1,785 domestic violence crime reports generated by the Colorado
      Springs Police Department found that 1 in 6 (16.5 percent) contained evidence the
      suspect stalked the victim. Female victims were significantly more likely than
      male victims to allege stalking by their partners (18.3 vs. 10.5 percent). Most
      stalkers were former rather than current intimates. Regardless of victims'
      gender, reports with stalking allegations were significantly less likely to
      mention physical abuse or victim injury in the presenting condition, to involve
      households with children, or to involve victims and suspects who were using
      alcohol at the time of the report. Female victims who alleged stalking by their
      partner were significantly less likely than female victims who did not allege
      stalking to be emotionally distraught at the time of the report, but
      significantly more likely to have an active restraining order against the
      suspect, and to sign releases to facilitate the police investigation. Police
      almost never charged domestic violence stalking suspects with stalking,
      preferring instead to charge them with harassment or violation of a restraining
      order.

PMID- 11288941
TI  - Negative family-of-origin experiences: are they associated with perpetrating
      unwanted pursuit behaviors?
AB  - Parental divorce, history of parental relationship separation, perceptions of
      interparental conflict, and witnessing parental violence were retrospectively
      assessed in a sample of 213 college students from several regions in the United
      States, all of whom had suffered an unwanted break-up of an important romantic
      relationship. This study investigated whether these family-of-origin experiences
      were associated with perpetrating unwanted pursuit behaviors after the
      relationship break-up. Results indicated that male participants who had
      experienced either parental divorce or separation perpetrated more severe
      unwanted pursuit behavior than males who had not experienced parental divorce or
      separation or females from either divorced, separated, or intact families. For
      females, severe unwanted pursuit behavior perpetration was correlated with
      threatening and intense parental arguments. These findings suggest that a variety
      of types of negative parental relationship behavior may be risk factors for
      perpetrating severe unwanted pursuit behaviors. The gender-specificity and
      implications of these findings are discussed.

PMID- 11288940
TI  - The impact of severe stalking experienced by acutely battered women: an
      examination of violence, psychological symptoms and strategic responding.
AB  - Stalking has been relatively understudied compared to other dimensions of
      intimate partner violence. The purpose of this article was to examine concurrent
      and subsequent intimate partner abuse, strategic responses and symptomatic
      consequences of severe stalking experienced by battered women. Thirty-five
      battered women classified as "relentlessly stalked" and 31 infrequently stalked
      battered women were compared. Compared to infrequently stalked battered women,
      relentlessly stalked battered women reported: (a) more severe concurrent physical
      violence, sexual assault and emotional abuse: (b) increased post-separation
      assault and stalking; (c) increased rates of depression and PTSD; and (d) more
      extensive use of strategic responses to abuse. Results underscore the scope and
      magnitude of stalking faced by battered women and have implications for
      assessment and intervention strategies.

PMID- 11288942
TI  - Research on stalking: what do we know and where do we go?
AB  - Findings of the article in this two-volume series on stalking are reviewed.
      Building on the findings of the National Violence Against Women Survey (Tjaden &
      Thoennes, 1998), this series of studies adds to the literature in defining and
      measuring stalking behaviors. Repeated stalking victimization is reported by up
      to 62% of young adults, although frequencies depend on the sample and the precise
      definition used. Self-definitions of stalking victimization may be quite
      different from legal definitions. Although the majority of legally defined
      stalkers (where victim fear is a key component) are men stalking women, studies
      utilizing other definitions find many more women as stalkers, with no significant
      gender differences in many studies. In many cases, it does appear that stalking
      is one part of a larger pattern of relationship physical and psychological abuse.
      Data on emotional reactions and coping strategies of victims are also reviewed,
      along with findings on characteristics of stalkers.

PMID- 11288943
TI  - Cost-effectiveness of currently accepted strategies for pulmonary embolism
      diagnosis.
AB  - Improvements in the methods of clinical trials combined with the use of objective
      tests to detect venous thrombosis have enhanced the clinician's ability to
      diagnose pulmonary embolism and venous thrombosis (venous thromboembolism). The
      authors updated a previous cost-effectiveness analysis of the commonly
      recommended strategies for pulmonary embolism diagnosis and management to reflect
      current clinical practice. Two criteria of effectiveness were used: correct
      identification of venous thromboembolism and correct identification of venous
      thromboembolism and correct identification of patients for whom treatment was
      unnecessary. The cost of each diagnostic alternative was defined as the direct
      cost of administering the diagnostic tests plus the treatment costs associated
      with a positive test result. A strategy based on the combined use ofventilation
      perfusion lung scanning, serial ultrasonography, cardiorespiratory evaluation,
      and pulmonary angiography was the most cost-effective. This strategy also
      necessitated pulmonary angiography in the fewest number of patients. The safety
      of this strategy relates to two important biologic concepts: 1) local extension
      of submassive pulmonary embolism in the lung is not an important cause of
      morbidity or mortality in patients with adequate cardiorespiratory reserve, and
      2) in most patients, proximal vein thrombi of the lower extremities are the
      source of recurrent pulmonary embolism.

PMID- 11288944
TI  - Diagnosis of pulmonary embolism in outpatients by sequential noninvasive tools.
AB  - Considerable progress has been made in pulmonary embolism (PE) diagnosis during
      the last 10 years. New, noninvasive tools such as D-dimer measurement and lower
      limb venous compression ultrasonography have been introduced as diagnostic
      strategies. Clinical evaluation of the likelihood of PE has been rehabilitated
      and has proven to be accurate and useful. The interpretation of lung scan results
      has become more standardized and clear to clinicians. Finally, two diagnostic
      strategies have been validated in large scale outcome studies. Both rely on a
      sequential combination of the aforementioned instruments and have safely treated
      more than 90% of patients without use of pulmonary angiography. The 3-month
      venous thromboembolic risk in patients in whom PE was ruled out and, hence, who
      did not undergo anticoagulation was less than 1% in both studies. In the absence
      of a formal comparison of their respective cost-effectiveness, choosing between
      these strategies rests on local preferences or logistics. Finally, spiral
      computed tomography (CT) seems promising and might modify the diagnostic work-up
      of PE in the near future. However, it is insufficiently validated, and its place
      in a rational diagnostic algorithm is not defined.

PMID- 11288945
TI  - Noninvasive diagnosis of deep vein thrombosis in postoperative patients.
AB  - The accuracy of noninvasive testing for the diagnosis of deep vein thrombosis
      (DVT) generally is less in asymptomatic patients than it is in those with
      symptoms suggestive of thrombosis. This is because asymptomatic DVT often is
      confined to the distal veins and, when it involves the proximal veins, the
      thrombi usually are smaller than in symptomatic patients with proximal
      thrombosis. Because the positive predictive value of noninvasive tests for
      asymptomatic DVT generally is 80% or less, abnormal results should be confirmed
      by venography. There are two main reasons why asymptomatic DVT is sought in the
      postoperative period: (1) to identify the need for full-dose anticoagulant
      therapy to prevent symptomatic episodes of venous thromboembolism (VTE),
      including fatal pulmonary embolism (this represents a form of secondary
      prophylaxis), and (2) to use this outcome as a surrogate for episodes of
      clinically important VTE in studies that are designed to evaluate methods of
      venous thrombosis prophylaxis. In relation to the first of these indications,
      evidence suggests that routine surveillance of high-risk patients to detect
      asymptomatic postoperative DVT does not result in improved clinical outcomes in
      patients who received appropriate VTE prophylaxis. In relation to the second
      indication, there is concern that asymptomatic VTE may not be a reliable
      surrogate for clinically important VTE, particularly if the effectiveness of
      different antithrombotic agents is being compared. Coupled with the comparatively
      low accuracy of noninvasive testing for asymptomatic DVT, this suggests that the
      results of such testing are unsuitable for the evaluation of new methods of
      prophylaxis in clinical trials.

PMID- 11288946
TI  - Contrast-enhanced spiral computed tomography of the pulmonary arteries: an
      overview.
AB  - Spiral computed tomography is a new noninvasive diagnostic test for pulmonary
      embolism. The method provides tomographic images of the thorax in the axial
      plane, which depict the thoracic wall, the mediastinum, the lungs, and the
      pulmonary vessels. Thrombotic emboli in the vessels are seen as intraluminal
      filling defects in the contrast-enhanced pulmonary arteries. The physical
      principles of spiral computed tomography and several technical considerations
      concerning image quality will be briefly discussed. The accuracy of spiral
      computed tomography in the detection of pulmonary embolism is discussed by way of
      an overview of published validation and clinical outcome studies encompassing
      spiral computed tomography and the diagnosis of pulmonary embolism.

PMID- 11288947
TI  - End points in studies on the prevention of deep vein thrombosis.
AB  - Clinically overt events are of obvious relevance for the outcome of patients.
      There is unanimous consensus of clinicians that these events should be prevented
      in clinical practice. In clinical trials on the prevention of deep vein
      thrombosis, symptomatic objectively confirmed venous thromboembolism is the most
      important outcome to be measured. However, because of the difficulties related to
      the measurement of clinically overt events, venography is the most commonly used
      method for end-point measurement in clinical trials on the prevention of venous
      thromboembolism. The limitations of venography leave a great need for the
      development of accurate noninvasive methods to be used as alternatives to
      venography. The end point must be tailored to the phase of the clinical trial. In
      phase I/II clinical trials, that are designed to evaluate the effectiveness of
      thromboprophylactic agents, it still is necessary to use the most accurate method
      for the diagnosis of deep vein thrombosis and to perform bilateral venography.
      When a new pharmacologic agent is compared with the "gold standard" agent, the
      use of symptomatic end points should be preferable.

PMID- 11288948
TI  - Thromboembolism occurrence and diagnosis in the medical intensive care unit.
AB  - Venous thromboembolism (VTE) represents an unrelenting and formidable challenge
      in the critical care setting even for the most experienced clinician. The
      morbidity and mortality attributed to untreated VTE have been substantiated by
      increasing series of epidemiologic and postmortem studies. As a larger group of
      the general population grows older, with increasing requirements for critical
      care services, challenges for the intensivist in the diagnosis and management of
      VTE are expected to grow. Moreover, despite the tremendous development of many
      critical care technologies, complexities of medical conditions commonly
      encountered in the critically ill have detracted from suspicion of VTE and made
      prompt recognition difficult. The approach to diagnosis of VTE should optimize
      diagnostic yield and outcomes with responsible use of resources. Key to an
      appropriate approach of VTE diagnosis in the intensive care unit is an
      understanding of the predisposing risk factors--pretest probability and the
      strengths and weaknesses of available diagnostic tools. Rational use of
      ultrasound, impedance plethysmography, computed tomography (CT),
      echocardiography, contrast venography, angiography, and D-dimer assays have
      provided the clinicians with a more substantial armamentarium, albeit incomplete,
      to facilitate diagnosis of VTE. The best use of these diagnostic tests often are
      dependent on local availability and expertise as part of a multidisciplinary
      team. With application of sound clinical principles in identifying select
      patients at risk and disciplined use of diagnostic technologies using simple
      algorithms, improvements in the diagnosis and management of VTE in the intensive
      care unit may be expected.

PMID- 11288949
TI  - Long-term clinical course of proximal deep venous thrombosis and detection of
      recurrent thrombosis.
AB  - Symptomatic proximal deep vein thrombosis of lower extremities carries a high
      risk for recurrent venous thromboembolism that persists for many years. This risk
      is dependent on readily identifiable risk factors, being low after a trauma or a
      surgical intervention and higher in all the other patient categories. Moreover,
      postthrombotic sequelae will develop in one of every three patients, this risk
      being strongly related to the development of ipsilateral thrombosis. Although the
      optimal duration of anticoagulation in patients who experience an episode of
      proximal vein thrombosis is unknown, it seems reasonable to administer a short
      term course of coumarin drugs to patients with thrombosis associated with
      transient risk factors, whereas a longer course (6 to 12 months) should be
      considered in patients with idiopathic thrombosis and in those with permanent
      risk factors. Indefinite anticoagulant therapy is a clinical judgement in the
      individual patient. The management of patients who develop clinical
      manifestations suggestive of recurrent ipsilateral venous thrombosis still
      represents a challenge for clinicians. Recent data suggest that these patients
      can be safely managed with the use of serial compression ultrasonography.

PMID- 11288950
TI  - Will the "new biology" affect the future of histopathology?
AB  - The technologies used in histopathology are changing as a consequence of the
      current revolutionary progress in several areas of biology. It is likely that
      general cancer management will improve because of the impact of molecular
      techniques and immunohistochemistry on tumor diagnosis and classification and on
      the determination of prognosis and response to therapy. Moreover, as therapies
      are starting to be modelled after the distinctive molecular characteristics of a
      specific tumor, the availability of molecular tests to all patients will become a
      matter of great importance.

PMID- 11288951
TI  - Relationship between mesenteric and peripheral blood levels of CA 19-9 in
      patients with colorectal cancer.
AB  - INTRODUCTION: CA19-9 is one of the most important tumor markers used in patients
      with colorectal cancer, mainly in radical surgery follow-up. AIM: The purpose of
      this study was to evaluate the preoperative CA19-9 level obtained from a
      peripheral vein (PV) and compare it to the level obtained from the mesenteric
      vein (MV). MATERIALS AND METHODS: Blood was collected from a PV of the arm and
      from the MV of 59 patients with colorectal cancer before primary surgery. Of
      these 59 patients fourteen had stage I disease, 10 stage II, 22 stage III, and 13
      stage IV. CA19-9 was determined in serum by immunoenzymatic assay (Abbott
      Diagnostica). RESULTS: Fifteen patients (24%) had elevated serum levels of CA19-9
      in the MV and 13 (22%) in the PV. None of the stage I or II patients had elevated
      serum levels of CA19-9. There were no differences between marker levels in blood
      collected from the MV or PV, independent of clinical stage. The CA19-9 values
      obtained from the MV differed significantly in the different stages of the
      disease according to the Kruskal-Wallis analysis (p=0.026); this difference was
      not statistically significant (p=0.08) in serum from the PV. There was no
      correlation between venous infiltration by the tumor and positivity of CA19-9
      serum levels collected from the mesenteric vein. We observed a close correlation
      between the serum levels of CA19-9 collected from the PV and from the MV (r=0.9).
      CONCLUSION: The current study demonstrates a close correlation between the serum
      levels of CA19-9 collected from a peripheral vein and from the mesenteric vein.
      Our results confirmed the poor sensitivity of serum CA19-9 at diagnosis,
      independent of the collection site.

PMID- 11288952
TI  - Expression and clinical significance of pepsinogen C in resectable pancreatic
      cancer.
AB  - Pepsinogen C is an aspartyl-proteinase usually involved in the digestion of
      proteins in the stomach, and an androgen- inducible protein in breast cancer
      cells. In this study we evaluated its expression and clinical significance in
      patients with resectable pancreatic cancer. Pepsinogen C expression was examined
      by immunohistochemical methods in a series of 73 pancreatic carcinomas. The
      prognostic value of pepsinogen C was retrospectively evaluated by multivariate
      analysis. A total of 21 (28.8%) pancreatic carcinomas stained positively for
      pepsinogen C. The percentage of pepsinogen C-positive tumors was significantly
      higher in well-differentiated tumors (38.3%) than in moderately differentiated
      (15.8%) and poorly differentiated (O%) tumors (p<0.05). In addition, statistical
      analysis revealed that pepsinogen C expression was associated with clinical
      outcome. Thus, patients with pepsinogen C-negative tumors have a poorer overall
      survival than those with pepsinogen C-positive tumors. Our results led us to
      consider that the expression of pepsinogen C may represent a useful biological
      marker in pancreatic cancer. Expression of this protein may be a marker of
      gastric-type differentiation of the tumors and it might also reflect the
      existence of a complete hormone receptor pathway in a subset of pancreatic
      carcinomas.

PMID- 11288953
TI  - Prognostic significance of cytosolic pS2 protein content in gastric cancer.
AB  - pS2, a 60-amino-acid chain peptide which is the most widespread estrogen-induced
      RNA messenger in MCF-7 breast cancer cells, is normally detected in the
      epithelium of gastric mucosa. The aims of this work were to evaluate the
      cytosolic pS2 content and its clinical significance in gastric carcinomas.
      Cytosolic pS2 levels were examined by immunoradiometric methods in 108 patients
      with primary gastric adenocarcinomas. The mean follow-up period was 23.3 months.
      The cytosolic pS2 levels of the tumors ranged widely, i.e., from 0.1 to 3217
      ng/mg protein. There were no significant differences in pS2 content between
      tumors (mean +/- standard error: 137.2+/-31.4 ng/mg protein) and paired adjacent
      mucosa samples (n=84; mean +/- standard error: 249.6+/-32.6 ng/mg protein), nor
      were there any significant differences in tumoral pS2 levels with respect to
      clinicopathologic parameters such as patient age and sex or tumor location,
      stage, histologic type or grade. However, the results indicated that high
      intratumoral pS2 levels were significantly and independently associated with an
      unfavorable outcome in the overall group of patients (p=0.0266) and in patients
      with resectable gastric cancer (p=0.003). In conclusion, pS2 may represent a
      useful biological marker in gastric cancer.

PMID- 11288954
TI  - Use of a variety of biological parameters in distinguishing cirrhotic from
      malignant ascites.
AB  - Twenty-two different protein measurements were taken in the serum and ascitic
      fluid of fifty consecutive patients in an attempt to investigate which tests are
      the most reliable for the differential diagnosis of ascites. Serum and ascitic
      fluid total proteins (TPR), albumin (ALB), lactate (LAC), ferritin (FER), C3 and
      C4 complement factors, C-reactive protein (CRP), ceruloplasmin (CER), alpha2
      macroglobulin (alpha2MG), haptoglobin (HAP), alpha1-antitrypsin (alpha1AT),
      alpha1-acid glycoprotein (alpha1AG), transferrin (TRF), immunoglobulins IgG, IgA,
      IgM and cytokines such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL
      1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8) and
      tumor necrosis factor-alpha (TNF-alpha) were measured to distinguish between
      malignant and cirrhotic ascites. Correlations and non-parametric Mann-Whitney
      tests were used for ascitic fluid:serum ratio comparisons between the two groups.
      Multivariate analyses were used to determine the most significant biochemical
      ratio predictors for the differential diagnosis and a recursive partitioning
      model was constructed. Highly positive correlations (r>0.50) were found between
      the ratios IgA, IgG, IgM, CER, alpha2 MG, HAP, alpha1AT, alpha1AG and TRF. There
      was evidence that TPR, ALB, LAC, FER, IgG, CER, alpha2MG, alpha1AT, alpha1AG, TRF
      and IL-8 ascitic fluid:serum ratios are significnatly higher in patients with
      malignant neoplasms than in cirrhotics. In the recursive partitioning model the
      most significant parameters were found to be the ratios of albumin and IL-1alpha.
      The model fitted allowed for 100% correct classification of ascites. In
      conclusion, we have shown that a simple and very accurate model based on two
      ascitic fluid: serum measurements is able to differentiate between malignant and
      non-malignant ascites.

PMID- 11288955
TI  - Circulating angiogenesis regulators in cancer patients.
AB  - BACKGROUND/AIMS: To date, numerous studies have demonstrated that several
      angiogenesis regulators circulate in the blood and may function as endocrine
      factors in cancer patients. This review aims to give a comprehensive insight into
      the possible clinical value of circulating angiogenesis regulators, mainly basic
      fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and
      hepatocyte growth factor (HGF), angiogenin, pleiotrophin, thrombospondin (TSP)
      and endostatin (ES) in cancer patients. METHODS: A computerized (MEDLINE) and a
      manual search based on the reference lists of the publications were performed to
      identify articles published on this topic. RESULTS: In a detailed literature
      search, approximately 100 publications were found up to the end of 1999.
      Circulating angiogenic factors such as bFGF, VEGF, HGF and angiogenin have been
      evaluated not only as diagnostic and/or prognostic factors but also as predictive
      factors in cancer patients. On the other hand, little is known about the clinical
      significance of negative regulators. Neither the source nor the mechanism of
      protein externalization has been clarified in detail. CONCLUSIONS: Although there
      are no known factors with established clinical utility, circulating angiogenesis
      regulators may be useful in several situations. They could be used to determine
      the risk of developing cancer, to screen for early detection, to distinguish
      benign from malignant disease, and to distinguish between different types of
      malignancies. In patients with established malignancies such factors might be
      used to determine prognosis, to predict the response to therapy, and to monitor
      the clinical course. Further investigations are warranted to assess the specific
      utility of each factor.

PMID- 11288956
TI  - Immunoradiometric assay of chromogranin A in the diagnosis of small cell lung
      cancer: comparative evaluation with neuron-specific enolase.
AB  - The aims of our work were 1) to determine the diagnostic performance of an
      immunoradiometric assay of chromogranin A (CgA) in small cell lung cancer and 2)
      to compare its discriminatory power with that of neuron-specific enolase (NSE),
      the marker currently used for SCLC. We selected 166 cases of small cell (64) and
      non-small cell (102) lung cancer and 106 cases of non-malignant lung diseases as
      controls. Both CgA and NSE were assayed by immunoradiometric methods and cutoff
      values were established on the basis of a pre-fixed specificity of 95% in non
      malignant lung diseases. The CgA assay showed better diagnostic sensitivity than
      NSE in SCLC (61% versus 57%), especially in limited disease, and a low positivity
      rate in NSCLC with respect to NSE (14% versus 22%). By contrast, NSE reflected
      disease extent more accurately than CgA (U test: CgA p<0.05, NSE p<0.001).
      Finally, we found that the CgA assay was not affected by hemolysis whereas NSE
      serum levels greatly increased in hemolyzed sera. In conclusion, CgA assaying by
      an IRMA method is a reliable procedure in the diagnosis of SCLC. NSE remains the
      marker of choice in staging and monitoring of the disease. Further studies are
      needed to evaluate the prognostic significance of the marker and its role in
      therapy monitoring and patient follow-up.

PMID- 11288957
TI  - Histological grade in breast cancer: association with clinical and biological
      features in a series of 229 patients.
AB  - In order to study the association of histological grade (HG) with specific
      clinical and biological parameters which may influence the clinical behavior of
      infiltrating ductal carcinomas of the breast (IDC), we analyzed in 229 tissue
      samples the cytosolic concentrations of estrogen receptor (ER), progesterone
      receptor (PR), pS2, cathepsin D, hyaluronic acid (HA) and tissue-type plasminogen
      activator (t-PA), as well as those of the erbB2 oncoprotein, epidermal growth
      factor receptor (EGFR), HA, CD44v5 and CD44v6 in the cell membrane fraction.
      Likewise, we considered size, ploidy, S-phase fraction and axillary node
      involvement as variables of the study. The transition from HG1 to HG2 and from
      HG2 to HG3 was accompanied by a number of common features: global increase in
      size, greater number of tumors >2.0 cm, decrease in membrane hyaluronic acid
      concentrations, increased cell proliferation (S-phase >7%) and greater
      aneuploidy. Other events observed during the transition from HG2 to HG3 were a
      decrease in ER, PR, t-PA and cytosolic hyaluronic acid. These results led us to
      consider that HG is associated with certain clinical-biological changes that may
      help explain its value as a prognostic factor in breast carcinomas.

PMID- 11288958
TI  - Prognostic significance of the combined expression of matrix metalloproteinase-9,
      urokinase type plasminogen activator and its receptor in breast cancer as
      measured by Northern blot analysis.
AB  - Using Northern blot analysis we have measured the co-expression of the matrix
      metalloprotease MMP-9, plasminogen activator urokinase type (uPA) and its
      receptor (uPAR) mRNAs in 81 biopsies of breast carcinomas with the objective of
      analyzing the impact of these factors on the overall survival probability of the
      patients (median follow-up time: 4 years). Individual mRNA levels of either uPA
      or uPAR showed parallel variations with MMP-9 mRNA, suggesting a coordinate
      transcription of these markers. When median values were used as cutoff points to
      discriminate between high and low factor expression, no association was found
      with patient outcome and MMP-9 or uPA mRNA distribution. However, increased uPAR
      mRNA levels were associated with poor prognosis (p = 0.01). The combination of
      MMP-9 and uPAR mRNA measurements has not enhanced prognostic information compared
      to information supplied by the receptor alone (p = 0.01). The combination of MMP
      9 and high levels of uPA mRNA led to a significant association with poor outcome
      (p = 0.03). Multivariate analysis supported the notion that increased uPAR mRNA
      production in primary breast cancer may be a predictor of overall survival.

PMID- 11288959
TI  - HER-2/neu serum levels and menopausal status.

PMID- 11288960
TI  - Drug therapy tailored for the individual patient--search for the holy grail.

PMID- 11288961
TI  - Can cocaine abuse exacerbate the cardiac toxicity of human immunodeficiency
      virus?
AB  - Both cocaine use and human immunodeficiency virus (HIV) infection alone have been
      associated with an increased incidence of cardiac dysfunction. Concomitant
      exposure to cocaine and HIV infection may exacerbate the cardiac toxicity of
      either agent alone, a hypothesis that is examined in this review article. A
      possible unifying hypothesis based on enhancement of adrenergic stimulation is
      proposed.

PMID- 11288962
TI  - Angiotensin receptor blockers: evidence for preserving target organs.
AB  - Hypertension is a major problem throughout the developed world. Although current
      antihypertensive treatment regimens reduce morbidity and mortality, patients are
      often noncompliant, and medications may not completely normalize blood pressure.
      As a result, current therapy frequently does not prevent or reverse the
      cardiovascular remodeling that often occurs when blood pressure is chronically
      elevated. Blockade of the renin-angiotensin system (RAS) is effective in
      controlling hypertension and treating congestive heart failure. Both angiotensin
      converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)
      inhibit the activity of the RAS, but these two classes of antihypertensive
      medications have different mechanisms of action and different pharmacologic
      profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the
      production of angiotensin II (Ang II). In addition, angiotensin I is not the only
      substrate for ACE. The ACE inhibitors also block the degradation of bradykinin
      that may have potential benefits in cardiovascular disease. Bradykinin is,
      however, the presumed cause of cough associated with ACE inhibitor therapy. Data
      from clinical trials on ACE inhibitors serve to support the involvement of the
      RAS in the development of cardiovascular disease. Angiotensin receptor blockers
      act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively.
      Thus, ARBs are more specific agents and avoid many side effects. Experimental and
      clinical trials have documented the efficacy of ARBs in preserving target-organ
      function and reversing cardiovascular remodeling. In some instances, maximal
      benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors.
      This review describes clinical trials that document the efficacy of ARBs in
      protecting the myocardium, blood vessels, and renal vasculature.

PMID- 11288963
TI  - Early prediction of 30-day mortality after Q-wave myocardial infarction by
      echocardiographic assessment of left ventricular function--a pilot investigation.
AB  - BACKGROUND: The GUSTO angiographic substudy demonstrated that left ventricular
      function measured 90 min after thrombolytic therapy was given had important
      prognostic implications at 30 days in patients with an acute myocardial
      infarction (MI). HYPOTHESIS: Thirty-day prognosis after Q-wave MI can be
      determined by early echocardiographic assessment of left ventricular function.
      METHODS: Using transthoracic echocardiography, semiquantitative ejection fraction
      and wall motion score index was assessed prospectively in 201 consecutive
      patients within 24 h following Q-wave MI. Independent experts blinded to the
      patient's status performed the echocardiographic assessment. All patients
      received standard medical care as dictated by the attending cardiologist.
      RESULTS: Of the 201 patients, 24 (11.9%) died within 30 days, with 70% of the
      deaths occurring within 10 days after the infarction. Three deaths occurred in
      the 120 patients with an ejection fraction > or = 45% (2.5% mortality rate). In
      contrast, 21 deaths occurred among the 81 patients with an ejection fraction <45%
      (25.9% mortality rate) p = 0.0003. Two of the three patients who died in the high
      ejection fraction group died as a result of intracerebral hemorrhage from
      thrombolytic therapy. Ejection fraction was lower in nonsurvivors (32.3+/-10.3
      vs. 46.3+/-13%) than in survivors, p < 0.0002. Wall motion score index (WMSI) of
      < 1.4 was associated with a 2.9% 30-day mortality (two deaths in 76 patients);
      WMSI of > or = 1.4 was associated with a 17.6% 30-day mortality (22 deaths in 125
      patients), p = 0.0007. Average WMSI was higher in the nonsurvivors (1.95+/-0.5)
      than in survivors (1.52+/-0.45), p = 0.00001. CONCLUSIONS: Echocardiographic
      assessment of left ventricular function during the first 24 h after an acute Q
      wave MI can be performed in all patients regardless of stability. High-risk
      patients are identified early in the hospital course, with relative ease, at no
      risk and at an acceptable cost. An ejection fraction < 45% or WMSI > or = 1.4
      identifies patients who are at a high risk of dying within 30 days. These are the
      patients who may benefit most from aggressive medical therapy and early
      angiography to assess coronary pathology.

PMID- 11288964
TI  - Rescue use of abciximab improves regional left ventricular function after early
      incomplete reperfusion in acute myocardial infarction.
AB  - BACKGROUND: Abciximab was shown to have important beneficial effects beyond the
      maintenance of epicardial coronary artery patency. However, it remains uncertain
      whether abciximab may lead to a better functional outcome in patients with acute
      myocardial infarction (AMI) and with incomplete reperfusion after primary
      angioplasty (PA). HYPOTHESIS: The study aimed to evaluate whether rescue use of
      abciximab may lead to a better functional outcome in such patients. METHODS: The
      study included 25 patients with first AMI who met the following criteria: (1)
      total occlusion of the infarct-related artery, (2) PA within 12 h of symptom
      onset, (3) postprocedural diameter stenosis < 30%, and final Thrombolysis in
      Myocardial Infarction (TIMI) flow grade 2. Echocardiographic examination was
      performed before and on Days 7 and 30 after PA. The study population was divided
      into two groups: Group 1 (usual care, n = 13) and Group 2 (rescue use of
      abciximab, n = 12). Baseline characteristics were similar between the two groups.
      RESULTS: Peak level of creatine kinase was higher in Group 1 than in Group 2
      (5,800+/-2,700 vs. 3,800+/-2,000 U/I, p < 0.05). At 1 month follow-up, infarct
      zone wall motion score index (2.71+/-0.26 vs. 2.05+/-0.63, p < 0.01) and left
      ventricular (LV) volume indices were smaller in Group 2 than in Group 1, whereas
      LV ejection fraction was higher in Group 2 than in Group 1 (52.1+/-7.8 vs. 42.1+/
      6.4, p < 0.01). At 1-month, abciximab was the only independent predictor of wall
      motion recovery index by multiple regression analysis. CONCLUSIONS: Rescue use of
      abciximab may reduce the infarct size in patients with AMI and TIMI grade 2 flow
      after PA, which may improve the recovery of regional LV function.

PMID- 11288965
TI  - Myocardial bridging of the left anterior descending coronary artery in acute
      inferior wall myocardial infarction.
AB  - BACKGROUND: We observed marked myocardial bridging of the left anterior
      descending coronary artery (LAD) in the acute stages of inferior wall myocardial
      infarction (MI) in a group of patients who developed shock despite successful
      reperfusion of the infarct-related lesion (IRL). HYPOTHESIS: The purpose of this
      study was to elucidate the clinical significance of myocardial bridging in
      patients with inferior wall MI and shock. METHODS: The study group consisted of
      53 patients with single-vessel disease of the right coronary artery, who
      underwent coronary angiography for acute inferior wall MI. Clinical
      characteristics, coronary angiographic findings, and left ventricular function
      during the chronic phase were compared between the patients who developed shock
      (the shock group) and those who did not (the non-shock group). In addition, a
      multiple logistic analysis was performed to identify independent predictors of
      shock in patients with acute inferior wall MI. RESULTS: Reperfusion of the IRL
      was obtained in all 53 patients. The incidence of myocardial bridging of the LAD,
      the incidence of right ventricular MI, the peak creatine phosphokinase (CPK-MB).
      the pulmonary capillary wedge pressure, and the prevalence of pulmonary
      congestion seen on chest roentgenogram were significantly higher in the shock
      group than in the non-shock group. Myocardial bridging (p = 0.0018), right
      ventricular MI (p = 0.0374), and peak CPK-MB (p = 0.0189) were identified as
      independent predictors of shock in acute inferior wall MI. CONCLUSION: This study
      suggests that myocardial bridging plays a role in left ventricular function in
      the acute stage of inferior wall MI.

PMID- 11288966
TI  - Clinical characteristics of patients with increased urinary excretion of
      adrenaline in mild to moderate heart failure.
AB  - BACKGROUND: We have previously demonstrated that adrenaline (AD) is released into
      the circulation during acute myocardial infarction and is associated with a more
      severe clinical course. The role of elevated AD levels in congestive heart
      failure is not known. HYPOTHESIS: The study aimed to determine whether increased
      daily AD excretion is associated with more severe clinical symptoms and a more
      complicated clinical course in patients with exacerbation of congestive heart
      failure (CHF). METHODS: Urinary excretion of AD, noradrenaline, magnesium (Mg),
      and potassium (K), serum levels of aldosterone, K, and Mg, as well as the
      incidence of arrhythmias (24-h Holter) were assessed in 49 patients with CHF New
      York Heart Association (NYHA) class II-III. The patients were allocated to two
      groups, with normal (Group 1) and increased (Group 2) excretion of AD. RESULTS:
      Groups 1 and 2 did not differ in respect of age, etiology of CHF, or the
      medication used. Also, left ventricular ejection fraction was similar in the two
      groups. However, left ventricular end-diastolic dimension was greater in Group 2
      (61+/-9 vs. 55+/-11 mm, p<0.05), as was the proportion of patients in NYHA class
      III (74 vs. 40%). Group 2 was also characterized by increased urinary excretion
      of Mg (60+/-24 vs. 43+/-16 mg/24 h, p < 0.007) and the presence of more complex
      and numerous ventricular arrhythmias (74 vs. 37% and 68 vs. 33% of patients,
      respectively). CONCLUSIONS: Urinary excretion of AD is increased only in a
      subgroup of patients with CHF. These patients are characterized by a more
      advanced NYHA class, increased end-diastolic left ventricular diameter, and
      increased urinary excretion of magnesium. It is likely that all these factors
      contribute to the presence of more complex and numerous ventricular arrhythmias
      in this subgroup of patients.

PMID- 11288967
TI  - Efficacy of balloon valvuloplasty in patients with critical aortic stenosis and
      cardiogenic shock--the role of shock duration.
AB  - BACKGROUND: Because of limited long-term success, aortic balloon valvuloplasty is
      considered to be a palliative procedure, including patients at excessive risk for
      standard therapy-aortic valve replacement-that is, those in cardiogenic shock.
      HYPOTHESIS: The study was undertaken to evaluate the outcome of balloon
      valvuloplasty for critical aortic stenosis complicated by cardiogenic shock.
      METHODS: Over a 10-year-period, we followed 14 patients (age 74+/-11 years, range
      50-91) presenting in cardiogenic shock and critical aortic stenosis, who
      underwent valvuloplasty, together with 19 patients with critical aortic stenosis
      requiring urgent major noncardiac surgery. RESULTS: In patients in shock,
      calculated aortic valve area could be increased successfully by at least 0.3 cm2,
      from 0.38+/-0.09 to 0.81+/-0.12 cm2, with an insignificant increase in cardiac
      index from 1.89+/-0.33 to 2.01+/-0.41 l/min * m2. In-hospital mortality was 71%
      (10 patients). Two patients underwent valve replacement within 16 days and
      survived after 1 year, as did two patients refusing surgery. By multivariate
      logistic regression analysis, only an interval between onset of shock symptoms
      and valvuloplasty of > 48 h was significantly associated with fatal outcome (p <
      0.01). In those patients requiring noncardiac surgery, this was possible after
      valvuloplasty in 95% who survived 1 year after hospital discharge. One patient in
      this group died of pulmonary embolism the day after the procedure. CONCLUSION:
      These data support the concept of causal treatment in patients with cardiogenic
      shock, as well as in the setting of cardiogenic shock and critical aortic
      stenosis, at the earliest possible convenience.

PMID- 11288968
TI  - Detection of the "midband" lipoprotein in patients with coronary artery spasm.
AB  - BACKGROUND: Dyslipidemia in patients with coronary vasospasm has been
      characterized by a low level of high-density lipoprotein (HDL) cholesterol
      without elevation of low-density lipoprotein (LDL) cholesterol, distinct from
      patients with organic coronary artery disease. HYPOTHESIS: Disordered
      triglyceride-rich lipoprotein metabolism may be linked to the genesis of coronary
      artery spasm. METHODS: The incidence of the "midband" lipoprotein observed
      between very low-density lipoprotein (VLDL) and LDL bands in the polyacrylamide
      disc gel electrophoretic analysis was determined in 48 patients with coronary
      spastic angina (CSA), in 50 patients with stable effort angina and a significant
      fixed coronary stenosis (SEA), and in 40 control subjects without coronary artery
      disease (Control). RESULTS: The incidence was significantly (p<0.05) higher in
      CSA (71%) than in SEA (50%) and Control (25%). Smoking was significantly (p <
      0.05) more prevalent in CSA (77%) than in SEA (50%) and Control (50%). In SEA,
      serum levels of triglyceride and apoproteins C-II, C-III, and E were all
      significantly higher, and the serum level of HDL cholesterol was significantly
      lower in the midband-positive than in the midband-negative subgroup. In CSA, no
      significant differences were found in these serum levels between the midband
      positive and -negative subgroups, except for a significantly (p < 0.05) lower
      level of HDL cholesterol in the former. However, a significantly (p < 0.05)
      higher incidence of diabetes mellitus or impaired glucose tolerance was noted in
      the midband-positive (41%) than in the midband-negative subgroup (7%) in CSA. The
      incidence of the detected midband lipoprotein was significantly decreased in the
      blood samples obtained from 20 of CSA after a > 6-month angina-free period (70-
      >25%, p < 0.05). CONCLUSIONS: The midband lipoprotein was frequently detected in
      patients with coronary vasospasm, suggesting that dyslipidemia with disordered
      triglyceride-rich lipoprotein metabolism may be linked to the genesis of coronary
      artery spasm.

PMID- 11288969
TI  - Implications of the absence of ST-segment elevation in lead V4R in patients who
      have inferior wall acute myocardial infarction with right ventricular
      involvement.
AB  - BACKGROUND: ST-segment elevation of > or = 1.0 mm in lead V4R has been shown to
      be a reliable marker of right ventricular involvement (RVI), a strong predictor
      of a poor outcome in patients with inferior acute myocardial infarction (IMI).
      However, patients with no ST-segment elevation in lead V4R despite the presence
      of RVI have received little attention. HYPOTHESIS: The study was undertaken to
      study the clinical features of patients with no ST-segment elevation in lead V4R
      despite the presence of RVI, which means false negative, as such patients have
      received little attention in the past. METHODS: We studied 62 patients with a
      first IMI, who had total occlusion of the right coronary artery (RCA) proximal to
      the first right ventricular branch and successful reperfusion within 6 h from
      symptom onset, to examine the implications of the absence of ST-segment elevation
      in lead V4R despite the presence of RVI. RESULTS: A standard 12-lead
      electrocardiogram (ECG) and right precordial ECG (lead V4R) were recorded on
      admission, and three posterior chest ECGs (leads V7 to V9) were additionally
      recorded in 34 patients. Patients were classified according to the absence (Group
      1, n = 18) or presence (Group 2, n = 44) of ST-segment elevation of > or = 1.0 mm
      in lead V4R on admission. Patients in Group 1 had a greater ST-segment elevation
      in leads V7 to V9 (2.9+/-2.4 vs. 1.4+/-3.0 mm. p < 0.05), a higher frequency of a
      dominant RCA (defined as the distribution score > or = 0.7) (72 vs. 11%, p <
      0.001), and a higher peak creatine kinase level (3760+/-1548 vs. 2809+/-1824
      mU/ml, p < 0.05) than those in Group 2. CONCLUSIONS: In patients with IMI caused
      by the occlusion of the RCA proximal to the first right ventricular branch, no ST
      segment elevation in lead V4R can occur because of concomitant posterior
      involvement. In such patients, the incidence of RVI may be underestimated on the
      basis of ST-segment elevation in lead V4R.

PMID- 11288970
TI  - Dobutamine as bridge to angiotensin-converting enzyme inhibitor-nitrate therapy
      in endstage heart failure.
AB  - BACKGROUND: Intravenous inotropic intervention in congestive heart failure is
      generally associated with a poor prognosis and is largely used as a "bridge" to
      mechanical support or heart transplantation. HYPOTHESIS: We hypothesized that the
      inotropic support afforded by dobutamine may serve as a bridge to the
      introduction and intensification of angiotensin-converting enzyme (ACE) inhibitor
      nitrate therapy. METHODS: We studied the efficacy of transitioning inotrope
      dependent patients in endstage heart failure from intravenous dobutamine to high
      dose ACE inhibitor-nitrates, with 1-year follow-up. Forty-nine sequential
      dobutamine-dependent patients with left ventricular ejection fraction (LVEF) 17+/
      17% were treated with increasing lisinopril (1.9+/-1.5 to 46+/-28 mg/day) and
      isosorbide dinitrate (7+/-6 to 229+/-161 mg/day). Outpatient dobutamine was
      continued or repeat infusions pursued, as indicated, and dobutamine was tapered
      when feasible. RESULTS: During the following year, 14 of 49 patients required
      repeat dobutamine, with home treatment with dobutamine for 6.3+/-3.7 months (n =
      5). At 1 year, New York Heart Association (NYHA) classification improved from
      3.6+/-0.5 to 1.9+/-1.0, p < 0.0001; yearly hospitalizations fell from 2.7+/-2.3
      to 1.2+/-3.0, p = 0.02; and LVEF rose from 17+/-7% to 24+/-11%, p < 0.0001. At 1
      year, 14 patients who remained dobutamine dependent had significantly more severe
      symptoms than dobutamine-independent patients (n = 35). Transplant or death
      occurred in 7 of 14 patients with follow-up dobutamine, and in 5 of 35 patients
      free of subsequent dobutamine, p = 0.03. Patients with poor outcome (transplant n
      = 10, death n = 12) continued to be more limited (NYHA 2.7+/-0.9 vs. 1.7+/-0.9, p
      = 0.0002), with more follow-up hospitalizations (3.6+/-5.4 vs. 0.6+/-0.8, p =
      0.0004), and no improvement in LVEF (17+/-8vs. 28+/-11%, p = 0.003). CONCLUSIONS:
      Of the patients on dobutamine inotropic support, 70% were successfully
      transitioned to ACE inhibitor-nitrate therapy, with improved symptoms and LVEF,
      and with reduced hospitalizations and follow-up dobutamine or transplant. Thirty
      percent of patients with continued need for dobutamine had a significantly poorer
      1-year clinical outcome.

PMID- 11288971
TI  - Factors predicting success rate and recurrence of atrial fibrillation after first
      electrical cardioversion in patients with persistent atrial fibrillation.
AB  - BACKGROUND: The recurrence rate of atrial fibrillation (AF) after elective
      cardioversion is high. HYPOTHESIS: The study aimed to identify clinical
      predictors for successful electrical cardioversion and maintenance of sinus
      rhythm after a first electrical cardioversion in patients with persistent AF
      without concomitant antiarrhythmic drugs of class I and III. METHODS: Consecutive
      outpatients (n = 166) with persistent AF for > 1 month, scheduled for elective
      cardioversion, were prospectively included in the study. A clinical
      investigation, echocardiographic assay, and Holter electrocardiogram (ECG) before
      and ECG 4 weeks after cardioversion, were performed in all patients. RESULTS: The
      mean age of the patients was 68 years (range 45-83) and duration of AF was 5 (1
      48) months. Sinus rhythm was established in 124 (75%) patients. In multivariate
      analysis, only duration of AF < 6 months (p < 0.04, odds ratio [OR] 2.2, 95%
      confidence interval [CI] 1.1 to 4.7) and patients weight (p < 0.03, OR 2.3, 95%
      CI 1.1 to 4.8 for weight < 80 kg) were identified as independent predictors of
      successful cardioversion. At 4 weeks after cardioversion, only 46 (37%) of 124
      patients maintained sinus rhythm. Independent factors for maintenance of sinus
      rhythm, in multivariate analysis, were AF <3 months (p < 0.04, OR 2.5, 95% CI 1.1
      to 5.6), treatment with beta blockers (p < 0.00001, OR 7.0, 95% CI 3.0 to 16.3)
      or verapamil/diltiazem (p < 0.04, OR 3.6, 95% CI 1.1 to 12.1), and right atrial
      dimension < 37 mm (p < 0.02, OR 5.9, 95% CI 1.4 to 25.4). CONCLUSIONS: In
      patients with persistent AF, the patient's weight and the duration of AF are
      independent predictors for a successful cardioversion. Short duration of AF,
      treatment with beta blockers or verapamil/diltiazem, and right atrial
      area/dimension are independent predictors for maintenance of sinus rhythm.

PMID- 11288972
TI  - Magnetic resonance imaging of old myocardial infarction in young patients with a
      history of Kawasaki disease.
AB  - BACKGROUND: On magnetic resonance imaging (MRI) using gadolinium
      diethylenetriamine pentaacetic acid (Gd-DTPA) as contrast medium, images of
      infarct regions are enhanced in acute myocardial infarction (AMI). In old
      myocardial infarction (OMI), thinning of the myocardial walls is present, but
      images are no longer enhanced by Gd-DTPA. On the other hand, MI in children with
      a history of Kawasaki disease (KD), several differences from adult MI are
      observed. HYPOTHESIS: The aim of this study was to evaluate the lesions that
      result from OMI in children with a history of KD using MRI with Gd-DTPA as a
      contrast medium. METHODS: The subjects were 16 young patients with a history of
      KD who were diagnosed as having OMI. Of these, both thinning of the myocardial
      wall and MRI enhancement by Gd-DTPA were observed in 4 cases, thinning alone was
      observed in 6 cases, Gd-DTPA image enhancement alone was observed in 3 cases, and
      neither thinning nor Gd-DTPA image enhancement was observed in 3 cases. RESULTS:
      The Gd-DTPA-image-enhanced, OMI-induced lesions observed in patients with KD were
      different from those observed in adults; this might be attributable to histologic
      differences. CONCLUSION: Magnetic resonance imaging using Gd-DTPA can evaluate
      myocardial thinning and presence of circulation noninvasively at the same time
      and is considered to be useful for long-term follow up of the patients with KD
      and OMI.

PMID- 11288974
TI  - Three-dimensional visualization of nonobstructive coronary artery stenosis using
      electron beam tomography.

PMID- 11288973
TI  - Elevated plasma levels of interleukin-2 and soluble IL-2 receptor in ischemic
      heart disease.
AB  - BACKGROUND: T-lymphocytes are present in significant numbers in the
      atherosclerotic plaque, but their role in the progression and pathogenesis of
      coronary syndromes remains poorly understood. HYPOTHESIS: We sought to determine
      the relationship between T-lymphocyte activation and ischemic heart disease by
      measuring plasma levels of cytokines related to T-lymphocyte function in patients
      with stable and unstable angina. METHODS: Plasma levels of interleukin-2 (IL-2)
      and soluble IL-2 receptor (sIL-2R) were measured in 105 patients: 66 with stable
      angina, 24 with unstable angina, and 15 healthy controls. Patients who presented
      to the cardiac catheterization laboratory with unstable or stable anginal
      syndromes for coronary angiography or percutaneous coronary intervention enrolled
      in the study. RESULTS: Mean levels of IL-2 were significantly higher in patients
      with stable angina than in those with unstable angina. The differences between
      stable angina and control groups, or between unstable angina and control groups,
      were not statistically significant. Mean levels of slL-2R were significantly
      higher in patients with stable angina than in either patients with unstable
      angina or control patients. CONCLUSIONS: Levels of IL-2 and sIL-2 receptor are
      significantly elevated in patients with stable angina, but not in patients with
      unstable angina. The contribution of T-lymphocytes to the development of both
      stable and unstable angina requires further investigation.

PMID- 11288975
TI  - Histamine--can it cause an acute coronary event?
AB  - Myocardial infarction (MI) occurring during the course of an allergic urticarial
      reaction in the absence of systemic hypotension has been rarely reported. This
      paper reports the case of a 28-year-old woman with no significant risk factors
      for coronary artery disease who presented with generalized urticaria associated
      with chest pain and had electrocardiographic and enzymatic evidence of an acute
      MI. Review of the literature suggests that local histamine release may induce
      spasm of the coronary vasculature, thus leading to myocardial ischemia and
      infarction.

PMID- 11288976
TI  - Assessment of coronary morphology and flow in a patient with Guillain-Barre
      syndrome and ST-segment elevation.
AB  - Patients with Guillain-Barre syndrome often have cardiac disturbances as a
      manifestation of autonomic dysfunction. Such abnormalities consist of arrhythmias
      and disturbances of heart rate and blood pressure. We report a case of a patient
      with Guillain-Barre syndrome who developed ST-segment elevation in the
      inferolateral leads, suggestive of an acute coronary syndrome. Cardiac
      catheterization revealed angiographically normal coronary arteries. Intracoronary
      ultrasound was also normal. Intracoronary Doppler flow measurements revealed an
      elevated baseline coronary flow velocity of up to 41 cm/s and decreased coronary
      flow reserve, particularly in the left circumflex artery. Myopericarditis as
      cause of the electrocardiographic changes could be ruled out by echocardiography
      and endomyocardial biopsy. We postulate that the intracoronary Doppler findings
      are caused by autonomic dysfunction with decrease of coronary resistance and
      redistribution of the transmural myocardial blood flow.

PMID- 11288977
TI  - D. John Parker.

PMID- 11288978
TI  - Amiodarone stimulates interleukin-6 production in cultured human thyrocytes,
      exerting cytotoxic effects on thyroid follicles in suspension culture.
AB  - To investigate whether amiodarone increases interleukin-6 (IL-6) production in
      thyrocytes, human follicles obtained from subtotally thyroidectomized patients
      with Graves' disease were cultured in serum-free medium supplemented with various
      concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles
      gradually formed monolayer cells and secreted triiodothyronine (T3),
      thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-dependently increased
      T3 and Tg but not IL-6 levels in the conditioned medium. Amiodarone exerted no
      significant effect on T3, Tg, or IL-6 concentrations at 0.1-1 microM. In
      contrast, at 10-20 microM, it decreased T3 and Tg, but increased IL-6 levels, and
      these changes were accompanied by increased expression of IL-6 mRNA. Amiodarone
      induced IL-6 production was inhibited by prednisolone at 10(-7) M. Electron
      microscopic examination revealed that the thyroid follicles in the suspension
      culture remained intact at 1 microM, but that cytotoxic effects (decreased
      microvilli and increased onion-like inclusion bodies) occurred at higher
      concentrations (10-25 microM). These in vitro findings indicate that amiodarone
      does not impair thyroid function at clinically attainable serum levels (1
      microM), but exerts cytotoxic effect by inducing the production of a
      proinflammatory cytokine (IL-6) at higher concentrations. Because amiodarone
      induced IL-6 production was inhibited by prednisolone, it is reasonable to
      administer glucocorticoids to patients with amiodarone-induced destructive
      thyrotoxicosis (type II).

PMID- 11288979
TI  - Reassessment of the location of the thyrotropin receptor 50 amino acid
      "insertion" provides evidence in favor of a second downstream cleavage site.
AB  - Cleavage of thyrotropin receptors (TSHR) on the cell surface into disulfide
      linked A and B subunits involves deletion of an intervening region that
      corresponds approximately to a 50 amino acid "insertion" in the TSHR relative to
      the noncleaving luteinizing hormone/choriogonadotropin receptor (LH/CGR). The
      location of this insertion is imprecise because of the relatively low homology
      between the two receptors in this region. We tested the hypothesis that the TSHR
      50 amino acid insertion was further downstream than we previously concluded, a
      possibility that would relocate the crucial LH/CGR glycan at N291 relative to the
      position of the TSHR insertion, and that would mitigate against the 50 amino acid
      insertion playing a role in TSHR intramolecular cleavage. Thus, we transferred
      the LH/CGR glycan at amino acid 291 from downstream (N367) to upstream of the 50
      amino acid insertion (N317) in the TSHR, leaving this insertion intact. TSHR
      cleavage persisted. Moreover, deletion of amino acid residues 320-366 in addition
      to the upstream N291 substitution (ALN317-319NET) also did not prevent cleavage.
      On the other hand, deletion of three contiguous downstream residues (GQE367-369)
      in the TSHR 50 amino acid insertion abolished receptor cleavage into subunits. In
      summary, the present data are consistent with our previous location of the TSHR
      50 amino acid insertion and, therefore, do not undermine evidence for the
      involvement of this insertion in TSHR cleavage. In addition, the data regarding
      TSHR residues GQE367-369 (far downstream of cleavage site 1) support the
      controversial possibility of a secondary cleavage site downstream of the
      insertion.

PMID- 11288980
TI  - Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase
      controlled by thyroglobulin promoter demonstrates high specificity and low
      toxicity.
AB  - A replication defective adenovirus transducing thymidine kinase (TK) gene under
      the control of the rat thyroglobulin (rTg) promoter (AdrTgtk) was developed to
      evaluate its cell-specific killing activity in gene therapy. We also developed
      adenoviruses containing the TK gene driven by the cytomegalovirus (CMV) promoter
      (AdCMVtk), and luciferase (Luc) gene driven by the rTg or CMV promoter (AdrTgLuc
      or AdCMVLuc). Luc activity in FRTL-5, HepG2, COS1, rMTC, hMTC, Hela, GH3, T98G,
      and CA77 cells was measured after infection with AdrTgLuc or AdCMVLuc. FRTL-5
      cells produce thyroglobulin (Tg), whereas all other cells are non-Tg-producing
      cell lines. Transduction by AdCMVLuc caused high Luc activity in all cell lines.
      However, infection with AdrTgLuc induced Luc activity only in FRTL-5 cells.
      AdCMVtk or AdrTgtk was used to transduce various cell lines to evaluate the
      different killing effect. After infection with AdCMVtk vector followed by
      ganciclovir (GCV) treatment, cell growth was strongly suppressed in all cell
      lines compared both to noninfected cells and to cells infected by AdCMVLuc in the
      presence of GCV. When FRTL-5 cells were infected with AdrTgtk followed by GCV
      treatment, more than 90% were killed, but only a minimal effect was observed in
      other cell lines, indicating that the Tg promoter transduced TK expression only
      in Tg-producing cells. When adenovirus is given intravenously, liver and spleen
      are the major organs infected. A high Luc activity was found in liver and spleen
      of AdCMVLuc treated animals. No Luc activity was found in liver and spleen of
      AdrTgLuc-treated animals, indicating that rTg does not transduce Luc expression
      in non-Tg-producing tissues in vivo. No significant changes of the serum
      transaminase levels and histologic abnormalities were found in animals treated
      with AdrTgtk/GCV compared with control animals. High levels of serum
      transaminases, lymphocyte infiltration, some Kupffer's cell prominence, and
      extensive single cell hypatocyte death were found in AdCMVtk/GCV-treated animals,
      indicating severe liver damage induced, as expected, by a noncell-specific
      promoter. These results indicate that transfer of TK gene driven by the rTg
      promoter has thyroid cell-specific killing ability in the presence of GCV, little
      in vivo toxicity, and should be useful in the future for treating thyroid Tg
      producing cancers.

PMID- 11288981
TI  - Growth factor expression in cold and hot thyroid nodules.
AB  - Hot thyroid nodules (HTNs) are predominantly caused by constitutively activating
      thyrotropin receptor (TSHR) mutations leading to an activation of the cyclic
      adenosine monophosphate (cAMP)-cascade that stimulates growth and function of
      thyroid epithelial cells and confers growth advantage. In contrast to HTNs, the
      molecular etiology of szintigraphically cold thyroid nodules (CTNs) is largely
      unknown. An increased prevalence of toxic multinodular goiters in iodine
      deficient regions has been reported. Growth factors increase during early stages
      of iodine deficiency in rats. These growth factors could modulate the
      proliferation of thyrocytes. In order to determine if and which growth factors
      could modulate the increase in thyroid epithelial cell proliferation in late
      stages of CTNs and HTNs we investigated epidermal growth factor (EGF),
      transforming growth factor-alpha (TGF-alpha), and TGF-beta1 concentrations by
      enzyme-linked immunosorbant assay (ELISA) in CTNs (n = 7), HTNs (n = 9), and
      their normal surrounding tissue (ST). Insulin-like growth factor-1 (IGF-1) was
      determined in CTNs (n = 5) and HTNs (n = 10) and their surrounding tissues by
      radioimmunoassay (RIA). We found lower concentrations of all investigated growth
      factors and iodine in CTNs compared to surrounding normal tissues (ST). Only
      iodine showed a significant difference. Furthermore, we found significantly lower
      concentrations of EGF and TGF-beta1 concentration in HTNs compared to their STs.
      Differences of TGF-alpha and IGF-1 were not significant. In conclusion, low EGF,
      TGF-alpha, and IGF-1 concentrations in most CTNs in spite of low iodine
      concentrations argue against a pathophysiologic role of EGF, TGF-alpha, or IGF-1
      in late stages of CTNs. The low EGF, TGF-alpha, and IGF-1 concentrations in HTNs
      irrespective of their clonal origin or the presence or absence of activating
      mutations argue for increased cAMP as the primary cause for thyroid epithelial
      cell proliferation in established HTNs. However, the pathophysiologic
      significance of low TGF-beta1 concentrations in CTNs and HTNs remains to be
      elucidated. It might be possible that growth factors like EGF, TGF-alpha, TGF
      beta1, and IGF-1 play a more prominent role during early clonal expansion and
      that aberrant intrinsic signaling through a somatic mutation (e.g., TSHR for
      HTNs) confers the predominant selective growth advantage in later stages of HTNs
      or CTNs.

PMID- 11288982
TI  - Nuclear localization of epidermal growth factor and epidermal growth factor
      receptors in human thyroid tissues.
AB  - Epidermal growth factor (EGF) has widespread growth effects, and in some tissues
      proliferation is associated with the nuclear localization of EGF and epidermal
      growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs
      from thyrotropin (TSH) in inhibiting rather than stimulating functional
      parameters. We have therefore studied the occurrence and cellular distribution of
      EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated
      through the thyrotropin receptor (TSHR), and in a variety of human thyroid
      tumors. In the normal gland the staining was variable, but largely cytoplasmic,
      for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining
      for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF
      and particularly for EGFR was also a feature of both follicular adenomas and
      follicular carcinomas. Interestingly, nuclear staining was almost absent in
      papillary carcinomas. These findings document for the first time the presence of
      nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with
      increased growth (Graves' disease, follicular adenoma, and carcinoma) may
      indicate that nuclear EGF and EGFR play a role in growth regulation in these
      conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would
      suggest that the role played by EGF in growth control differs between papillary
      carcinoma and follicular adenomas/carcinomas of the thyroid.

PMID- 11288983
TI  - Analyses of MYC, ERBB2, and CCND1 genes in benign and malignant thyroid
      follicular cell tumors by real-time polymerase chain reaction.
AB  - The roles of the MYC, ERBB2, and CCND1 genes in thyroid carcinogenesis are poorly
      known. We used real-time quantitative polymerase chain reaction (PCR) assays
      based on fluorescent TaqMan methodology to quantify MYC, ERBB2, and CCND1 gene
      amplification and expression in 24 benign tumors (adenomas and goiter nodules)
      and 12 carcinomas (9 papillary, 2 follicular, and 1 anaplastic) of the thyroid.
      Real-time PCR is a recently developed method for nucleic acid quantification in
      homogeneous solutions, and has the potential to become a reference in terms of
      performance, accuracy, sensitivity, wide dynamic range, excellent interlaboratory
      agreement, and high throughput capacity, while avoiding the need for tedious post
      PCR processing. Overexpression (>5 standard deviations above mean for normal
      thyroid tissues) of the ERBB2 and CCND1 genes was observed (3.2- to 5.2-fold and
      3.8- to 8.4-fold, respectively) in 5 (14%) and 13 (36%) of 36 neoplastic thyroid
      RNA samples, respectively. Overexpression of the CCND1 gene was observed in both
      the benign and malignant thyroid tumors, whereas the ERBB2 gene was mainly
      overexpressed in malignant thyroid tumors. None of the neoplastic thyroid samples
      overexpressed MYC. No MYC, ERBB2, or CCND1 gene amplification was identified.
      These results suggest that the CCND1 gene plays an early role and the ERBB2 gene
      a later role in thyroid tumorigenesis.

PMID- 11288984
TI  - Endothelial function in patients with hyperthyroidism before and after treatment
      with propranolol and thiamazol.
AB  - Hyperthyroidism is associated with a higher incidence of arterial
      thromboembolism; increasing age, atrial fibrillation, and mitral valve
      abnormalities are risk factors. However, the contribution of endogenous
      coagulation parameters is unclear. Because thyroid hormone influences receptor
      and transcription factors, it can be expected that it will influence proteins
      involved in coagulation processes synthetised in many cells. Fourteen
      hyperthyroid patients were studied untreated, after 1 week of treatment with
      propranolol, and after therapeutic treatment with thiamazol. Fourteen matched
      controls were used for comparison. On each occasion, endothelial marker proteins,
      coagulation/fibrinolysis factors, and inflammatory (liver) markers were measured.
      Excess thyroid hormone was associated with elevated levels of most endothelium
      associated proteins. In addition, plasma fibronectin and fibrinogen were
      increased, while plasminogen was decreased. No evidence was found that
      hyperthyroidism was associated with coagulation/fibrinolysis activation, or with
      increased levels of the inflammation markers interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha) or C-reactive protein (CRP). Propranolol treatment only
      lowered the von Willebrand factor propeptide, and slightly increased plasminogen.
      Treatment with thiamazol returned all parameters to normal. Hyperthyroidism
      increased the plasma levels of most endothelial marker proteins, and of some
      liver-synthetized proteins. No evidence for coagulation/fibrinolysis activation
      was found. However, it appears that endothelial activation, which is indicative
      of a procoagulant state, is present in hyperthyroidism. This may explain the
      association between hyperthyroidism and thromboembolism especially if other risk
      factors are present. von Willebrand factor II (vWF:Ag-II) levels may be suitable
      markers to evaluate acute changes in endothelial function because this parameter
      responds more rapidly to changes in endothelial function than other factors.

PMID- 11288985
TI  - Endoscopic thyroidectomy for solitary thyroid nodules.
AB  - Conventional thyroidectomy often leaves an undesirable scar on the anterior neck.
      The aim of this study was to assess the feasibility and efficacy of endoscopic
      thyroidectomy, a new minimally invasive technique for thyroid surgery. Between
      September 1998 and February 2000, 18 patients with a solitary thyroid nodule
      underwent endoscopic thyroidectomy utilizing CO2 insufflation. There were 16
      females and 2 males with a mean age of 43 years (range 17-66 years). Indications
      for surgery included indeterminate cytology (n = 8), follicular neoplasm (n = 8),
      Hurthle cell neoplasm (n = 1), and toxic thyroid nodule (n = 1). The mean nodule
      diameter was 2.7 cm (0.6-7 cm). Analgesic requirement, return to normal activity,
      and cosmetic results were compared to 18 consecutive patients who had
      conventional thyroidectomy. Sixteen of 18 cases were successfully completed
      endoscopically with a mean operating time of 220 minutes (range, 120-330
      minutes). There were no major complications, but 3 patients developed mild
      hypercarbia and 1 patient had an incidental parathyroidectomy. When compared to
      conventional thyroidectomy, patients undergoing endoscopic thyroidectomy had a
      significantly superior cosmetic result (p < 0.005) and a quicker return to normal
      activity (p < 0.05), but there was no difference in analgesic requirement.
      Endoscopic thyroidectomy is a technically feasible and safe procedure that leads
      to an improved cosmetic result and a quicker recovery. Open completion
      thyroidectomy is recommended for thyroid carcinoma until more data are available.

PMID- 11288986
TI  - Keeping our eyes open.

PMID- 11288987
TI  - Unraveling the genetic susceptibility to autoimmune thyroid diseases: CTLA-4
      takes the stage.

PMID- 11288988
TI  - Association of DRB1*04-DQB1*0301 haplotype and lack of association of two
      polymorphic sites at CTLA-4 gene with Hashimoto's thyroiditis in an Italian
      population.
AB  - Hashimoto's thyroiditis (HT) is an autoimmune disease resulting from a complex
      interaction between genetic and environmental factors. The genetic loci
      conferring susceptibility need to be still defined. The aim of the present study
      was to determine whether Cytotoxic T-Lymphocyte-Associated Antigen-4 (CTLA-4),
      HLA DRB1, and DQB1 genes were associated to HT in an Italian population. We
      evaluated the allele distribution of the following loci: CTLA-4 exon 1 A49G
      dimorphism, which resulted in an amino acidic exchange (Thr/Ala) in the leader
      peptide, CTLA-4 3' microsatellite, HLA DRB1 and DQB1 in 126 patients with HT and
      in 301 control subjects from an Italian population (Lazio region). CTLA-4 exon 1
      A49G dimorphism was typed by Polymerase Chain Reaction and Restriction Fragment
      Length Polymorphism (PCR-RFLP); CTLA-4 3' microsatellite alleles were defined
      using a fluorescence-based method. HLA DRB1 and DQB1 alleles were typed using a
      SSO reverse line blot method and a probeless procedure based on allele group
      specific amplification followed by DNA heteroduplex analysis, respectively. Data
      were initially analyzed by chi2 test or Fisher's exact test. Multiple logistic
      regression analysis was then applied on factors with significant crude odds
      ratios and on CTLA-4 exon 1 A49G dimorphism to investigate their independent
      effects. The two polymorphic sites at CTLA-4 gene did not increase the risk for
      HT. The distribution of HLA DRB1 and DQB1 alleles did not show any significant
      difference between patients and controls, however, the DRB1*04-DQB1*0301
      haplotype was significantly increased in patients. Other factors that increase
      the risk of disease were gender and age. Females showed approximately 18 times
      more risk than males; subjects older than 50 years had an odds ratio of 6.6.
      These data suggest that these two polymorphic sites at CTLA-4 do not play a major
      role in the susceptibility of the disease in an Italian population while female
      gender, age over 50 years, HLA DRB1*04-DQB1*0301 haplotype increase the risk of
      developing HT.

PMID- 11288989
TI  - Identification of thyroglobulin in orbital tissues of patients with thyroid
      associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) is thought to have an autoimmune
      pathogenesis because of its association with autoimmune thyroid disease, in
      particular with Graves' disease. Nevertheless, the nature of the autoimmune
      reaction is unclear, and a target orbital autoantigen has not been conclusively
      identified. A widely discussed hypothesis is that antigens constitutively shared
      by the thyroid and orbital tissues are targets of an autoimmune reaction. It has
      been also postulated that a thyroid-soluble antigen, namely thyroglobulin (Tg),
      is transported to orbital tissues through the lymphatics, where it accumulates
      and elicits autoimmune damages in susceptible individuals. Here we have
      investigated whether Tg is present in orbital tissues from patients with TAO.
      Retrobulbar tissue specimens were obtained from three patients with Graves'
      disease and TAO who underwent decompressive orbitotomy, and at autopsy from two
      patients with no thyroid or eye disease. All patients with TAO had been
      previously treated with radioiodine to control Graves' hyperthyroidism. Western
      blot analysis with a monoclonal anti-Tg antibody showed the presence of intact
      Tg, both in soluble and membrane-associated fractions of orbital tissue extracts
      from the patients with TAO, in amounts estimated to range from approximately 320
      to approximately 900 pg/microg of tissue protein. In contrast, Tg was not
      detected in orbital tissue extracts from patients with no thyroid or eye disease.
      Tg was also demonstrated in orbital tissue extracts from two of three patients
      with TAO by enzyme-linked immunosorbent assay (ELISA), in amounts estimated to
      range from approximately 450 to approximately 1000 pg/microg of protein. In
      addition, Tg in orbital tissue extracts from patients with TAO was
      immunoprecipitated by a rabbit anti-Tg antibody, suggesting that it retained its
      native conformation. An anti-thyroxine (T4) antibody captured in solid-phase Tg
      from orbital tissue extracts, showing that it contained thyroid hormone residues
      and had therefore originated in the thyroid. Tg-anti-Tg immune complexes were not
      found in orbital tissues, suggesting that if an autoimmune reaction to Tg occurs
      in TAO, it is likely to be cell mediated.

PMID- 11288990
TI  - Surgical treatment of hyperthyroidism: a ten-year experience.
AB  - Hyperthyroidism is treated either by antithyroid drugs, radioiodine (I131) or
      surgery. In Sweden, surgery is often performed in patients with large goiter or
      severe hyperthyroidism with infiltrative endocrine ophthalmopathy. To evaluate
      indications and results of surgical treatment, data from 380 patients operated on
      for hyperthyroidism at our department during 1986-1995 were analyzed. Twenty-six
      percent were referred for surgery because of failure of treatment with
      antithyroid drugs or I131. Ninety-one percent were subjected to subtotal
      thyroidectomy with a median remnant weight of less than 2 g. In the remaining
      patients, total thyroidectomy was performed. Transient vocal cord affection
      occurred in 2.6%, none of which was permanent. Prolonged postoperative
      hypocalcemia occurred in 3.1%, and permanent hypoparathyroidism in 1%. There was
      no difference in complication rate between subtotal or total thyroidectomy. In
      patients with Graves' disease, 5% worsened with regard to ophthalmopathy
      initially after surgery but later improved. Recurrent disease occurred in 2% of
      the patients, all of whom had undergone subtotal thyroidectomy. Surgery is not
      first-line therapy in all patients with hyperthyroidism. However, in experienced
      hands, surgery is a good therapeutic alternative that can be carried out with no
      mortality, few complications, and, provided that a minimal remnant is left, very
      few recurrences.

PMID- 11288991
TI  - Cribriform variant papillary thyroid cancer: a characteristic of familial
      adenomatous polyposis.
AB  - Inherited cancer syndromes may predispose to more than one type of cancer, and
      these characteristically develop at an earlier age than their sporadic
      counterparts. The occurrence in a single individual of multiple, early onset
      primary cancers may indicate an inherited cancer susceptibility. Familial
      adenomatous polyposis (FAP), an autosomal, dominantly inherited susceptibility to
      colorectal adenomas and cancer also predisposes to childhood medulloblastomas and
      to a specific rare histologic type (cribriform variant) of papillary thyroid
      cancer. We describe a patient who developed a childhood medulloblastoma of the
      cerebellum, and subsequently a cribriform papillary thyroid cancer. These cancers
      predated the diagnosis of FAP in this patient, who was later found to have
      several relatives with FAP. The adenomatous polyposis coli (APC) mutation
      delineated in this family was in the region associated with those causing an
      increased risk of thyroid cancer. We submit that the diagnosis of the cribriform
      variant of papillary thyroid cancer in a young individual, especially after a
      previous cancer diagnosis, should alert the physician to the possibility of a
      diagnosis of FAP.

PMID- 11288992
TI  - Images in thyroidology. Vasculitis secondary to treatment with propylthiouracil.

PMID- 11288993
TI  - Hyperbaric oxygen therapy in acute necrotizing infections. With a special
      reference to the effects on tissue gas tensions.
AB  - Clostridial gas gangrene and perineal necrotizing fasciitis or Fournier's
      gangrene are rare but serious infections with an acute onset, rapid progression,
      systemic toxemia and a high mortality rate. The aim of this study was to
      investigate the efficacy of surgery, antibiotic treatment, surgical intensive
      care and in particular the role of hyperbaric oxygen (HBO) in the management of
      these infections. An experimental rat model was used to investigate the
      possibilities for measuring tissue oxygen and carbon dioxide tensions during
      hyperbaric oxygen treatment. In addition to this preliminary experimental study,
      Silastic tube tonometer and capillary sampling techniques were tested to measure
      the effect of hyperbaric oxygen treatment on subcutaneous oxygen and carbon
      dioxide tensions in patients with necrotizing fasciitis and healthy controls.
      Between January 1971 and April 1997, 53 patients with Clostridial gas gangrene
      were treated in the Department of Surgery, University of Turku. The patients
      underwent surgical debridement, broad spectrum antibiotic therapy and a series of
      hyperbaric oxygen treatments at 2.5 atmospheres absolute pressure (ATA). Twelve
      patients died (22.6%). Hyperbaric oxygen therapy in gas gangrene seems to be life
      , limb- and tissue saving. Early diagnosis remains essential. Patient survival
      can be improved if the disease is recognized early and appropriate therapy
      instituted promptly. Between February 1971 and September 1996, 33 patients with
      perineal necrotizing fasciitis were treated in the Department of Surgery,
      University of Turku. The management included surgical debridement of the necrotic
      tissue with incisions and drainage of the involved areas, antibiotic therapy,
      hyperbaric oxygen treatment at 2.5 ATA pressure and surgical intensive care.
      Three patients died giving a mortality rate of 9.1%. The survivors received
      hyperbaric oxygen therapy for 2-12 times. Our results indicate that hyperbaric
      oxygenation is an important therapeutic adjunct in the treatment of Fournier's
      gangrene. Electrical equipment should not be used unsheltered in a hyperbaric
      chamber due to the increased risk of fire. The subcutaneous tissue gas tensions
      of rats were therefore measured using a subcutaneously implanted Silastic tube
      tonometer and a capillary sampling technique. The method was succesfully adapted
      to hyperbaric conditions. The subcutaneous oxygen tension levels increased five
      fold and the carbon dioxide tension levels two fold compared to intial levels.
      The PO2 and PCO2 of subcutaneous tissue and arterial blood were measured directly
      in six patients with necrotizing fasciitis and three healthy volunteers in
      normobaric conditions and during hyperbaric oxygen exposure at 2.5 ATA pressure.
      The measurements were carried out in healthy tissue and at the same time in the
      vicinity of the infected area of the patients. During HBO at 2.5 ATA subcutaneous
      oxygen tensions increased several fold from baseline values and carbon dioxide
      tensions also increased, but to a lesser degree in both healthy and infected
      tissues. When examining the subcutaneous PO2 levels measured from patients with
      necrotizing fasciitis, the PO2 was regularly higher in the vicinity of the
      infected area than in healthy tissue. In general, HBO treatment resulted in a
      marked increase in tissue oxygenation in both healthy tissue and in the vicinity
      of infected tissue. The hyperoxygenated tissue zone surrounding the infected area
      may be of significance in preventing the extension of invading microorganisms.

PMID- 11288994
TI  - The Institute for Medical Research after 100 years.

PMID- 11288995
TI  - Malaria in Yuanyang, Yunnan, People's Republic of China--new control strategy
      (1992 -1996).

PMID- 11288996
TI  - Modeling factors influencing malaria incidence in Myanmar.
AB  - This is a documentary study to determine factors influencing malaria incidence in
      Myanmar. The period of study covered was from 1989 to 1998 using time series
      data. Multiple regression analysis was performed on the dependent variable,
      yearly incidence of malaria in Myanmar, with hypothesized independent variables
      including variables related to epidemiology, demography, service and
      socioeconomic status. Malaria incidence was inversely associated with the
      government budget for malaria control at the 5% level and with the case fatality
      rate of malaria at the 10% level. Other variables: yearly gross domestic product,
      yearly proportion of Plasmodium falciparum cases and yearly DDT use of spraying
      displayed expected signs but were not statistically significant.

PMID- 11288997
TI  - Characterization of specific monoclonal antibodies for detection of mefloquine in
      body fluids.
AB  - Specific monoclonal antibodies (MAbs) to mefloquine conjugated to bovine serum
      albumin (mefloquine-BSA) were produced by hybridoma technology. The mefloquine
      BSA was synthesized by converting mefloquine into hemisuccinate followed by
      convalently linked to bovine serum albumin (BSA) and coupling with N,N'
      disuccinimidyl carbonate (DSC). The conjugate was purified by Sephadex G-75 gel
      filtration using 0.01 M PBS pH 7.2. An average of 19.34 molecules of mefloquine
      were conjugated to each molecule of protein determined by differential UV
      absorption spectra of hapten and protein carrier. Sixteen monoclones producing
      antibody specific to mefloquine were screened by indirect ELISA using homologous
      antigens. The specificity of MAbs was determined by reacting with BSA and the
      structurally related antimalarial drug, quinine. Three, three, five and two MAbs
      belonged to IgG1, IgG2a, IgG2b and IgG3, respectively. Most of the MAbs slightly
      reacted with quinine-BSA due to the closely related structure of mefloquine to
      quinine. The selected MAb designated 11F9(G5)G9 which showed no cross reaction
      with quinine-BSA gave high reactivity with blood samples from malaria patients
      previously treated with mefloquine when compared to normal blood by indirect
      ELISA. The preliminary results indicated that such specific MAb could be used as
      antibody probe for detection of mefloquine in biological fluids.

PMID- 11288998
TI  - Promotion of insecticide-treated mosquito nets in Myanmar.
AB  - A simple health promotion message administered by village midwives raised bednet
      usage to over 60% in trial hamlets in north Shan State, Myanmar. Treatment of the
      nets in the study villages produced a reduction in malaria cases. Most villagers
      were prepared to buy their nets at market prices and were willing to pay for the
      cost of re-treatment of nets, but very poor, members of the Wa ethnic group
      required a half-price subsidy for them to afford them. The use of insecticide
      treated bednets was felt to be appropriate for undeveloped and remote areas of
      the country where malaria control was difficult.

PMID- 11289000
TI  - Prevalence of soil-transmitted helminth infections in the rural population of
      Bali, Indonesia.
AB  - The objectives of this cross-sectional study were to identify the prevalence of
      soil-transmitted helminth infection in the rural population of Bali and its
      relation to age, gender, and geoclimatic conditions. The subjects of study were
      derived from four villages of different geoclimatic conditions, namely wet
      lowland, dry lowland, wet highland and dry highland, by a multistage, stratified
      random sampling technique, based on age and gender of the target populations. The
      technique of Kato-Katz thick smear was used to determine presence of worm eggs in
      stools, and modified Harada Mori fecal culture technique was used to identify the
      species of hookworm larvae in stools. The data were analysed descriptively as
      well as statistically using chi2 test. Of 2,394 completely examined and analysed
      samples, the results showed as follows: The prevalences of Ascaris lumbricoides,
      Trichuris trichiura, hookworms and Strongyloides stercoralis were 73.7%, 62.6%,
      24.5%, 1.6%, respectively. Of 2,082 infected samples, 33.1% were single
      infections and 66.9% were mixed infections. Among the mixed infections,
      dualfection was most frequent (47.8%), followed by single infection (33.1%),
      triplefection (18.3%), and quadrifection (0.8%). A combination of A. lumbricoides
      and T. trichiura was predominant in dualfection, while in triplefection a
      combination of A. lumbricoides, T. trichiura, and hookworms was most frequently
      identified. The prevalence in males was not statistically different, except for
      hookworms where it was higher in males than in females. The differences of
      prevalence of infection according to age groups for A. lumbricoides, T. trichiura
      and hookworms proved to be highly significant, but not with Strongyloides
      stercoralis. The prevalence of hookworm infection increased steadily with age to
      reach its maximum (37.7%) in adulthood (> 18 years), while A. lumbricoides and T.
      trichiura reached the highest prevalence level in elementary school age (77.3%
      and 70.7% respectively). The highest prevalence of S. stercoralis infection was
      found also in elementary school age, but it was not statistically significant. In
      wet highland the prevalence of infection of A. lumbricoides was 87.6%, T.
      trichiura 82.4%, hookworms 44.5%, and S. stercoralis 3.3%; these were
      significantly higher compared to the prevalence of infection in other areas (wet
      lowland, dry highland, dry lowland).

PMID- 11288999
TI  - Epidemiology of human geohelminth infections (ascariasis, trichuriasis and
      necatoriasis) in Lushui and Puer Counties, Yunnan Province, China.
AB  - Between April and June of 1998, the prevalence and intensity of geohelminth
      infections caused by hookworm, Ascaris and Trichuris were investigated in two
      rural Yunnan villages. In Liuku, a village of Lisu indigenous people in Lushui
      County, there was an overall geohelminth prevalence of 72% (48%, 43% and 16% for
      hookworm infection, ascariasis, and trichuriasis, respectively). The prevalence
      of ascariasis was greatest among preschool and school aged children, whereas the
      prevalence of trichuriasis was greatest among teenagers and the prevalence of
      hookworm increased until the age of 10-15 and then remained high throughout
      adulthood. In Linger, a village of Han Chinese, located in Puer County, there was
      an overall geohelminth prevalence of 77% (30%, 60% and 36% for hookworm
      infection, ascariasis, and trichuriasis, respectively). The differences in
      prevalence for hookworm and ascariasis were statistically significant. The
      prevalence of hookworm in Linger increased steadily with age and did not plateau,
      but there were no discernible patterns of prevalence versus age for either
      ascariasis or trichuriasis. Heavy trichuriasis infections were noted to occur in
      Linger. In both villages, more than 98% of the hookworm infections were of light
      and moderate intensity. Both by morphologic identification of third-stage
      infective larvae (L3) from eggs as well as identification of adult hookworms
      recovered from adult residents after treatment with quantrel, Necator americanus
      was identified as the exclusive hookworm in each village. Geohelminth infections
      caused by Ascaris, Trichuris and hookworm remain highly endemic to the rural
      areas of Yunnan Province in southwestern China.

PMID- 11289001
TI  - Efficacy of multiple dose mebendazole against trichuriasis in Thai and Karen
      patients.
AB  - Treatment of trichuriasis with mebendazole 500 mg for three days, and 100 mg
      twice daily for three days, yielded cure rates of 93.9 and 88.9% in Thai
      patients, while the cure rates in Karen patients were 96.2 and 95.5%
      respectively. The total number of Thai and Karen trichuriasis patients were 60
      and 48, when tested by modified cellophane thick smear Kato-Katz technique. There
      were no significant differences among the two groups of patients and doses of
      treatment (p > 0.05).

PMID- 11289002
TI  - The effects of Trichinella spiralis infection on renal function in rats.
AB  - Trichinella spiralis infection was induced in rats by oral feeding of infective
      larvae. Four weeks later, renal function, including renal plasma flow (RPF),
      glomerular filtration rate (GFR), excretion rate of protein, sodium and potassium
      were determined using clearance technics. There were no significant changes in
      these parameters. However, plasma urea nitrogen was significantly higher in the
      infected group, suggesting that either an impaired regulation of renal tubular
      urea transport or an increased skeletal muscle breakdown is likely.

PMID- 11289003
TI  - The role of health education for schistosomiasis control in heavy endemic area of
      Poyang Lake region, People's Republic of China.
AB  - For exploring the impact of health education for schistosomiasis control in a
      heavy endemic area of Poyang Lake region, China, the residents residing in the
      heavy endemic area were divide into three kinds of target population: pupils,
      adult women and adult men, and then targeted health education was implemented
      respectively among the three kinds of population after a baseline survey. The
      result were compared with that in the control group. The anti-schistosomiasis
      knowledge level among the three kinds of population improved significantly, the
      correct rate of attitude to examination and chemotherapy among pupils and adult
      men and the correct rate of anti-schistosomiasis value concept among women were
      raised greatly, obedience to examination and chemotherapy among adult men
      increased, the rate of infested water exposure and infection rate among pupils
      and adult women declined remarkably. Therefore, infection with Schistosoma
      japonicum (Sj) can be controlled effectively among women, especially pupils and
      obedience to examination and chemotherapy among adults men can be improved by
      implementing health education.

PMID- 11289004
TI  - Comparative yield of different respiratory samples for diagnosis of Pneumocystis
      carinii infections in HIV-seropositive and seronegative individuals in India.
AB  - Respiratory specimens were prospectively examined for Pneumocystis carinii from
      53 patients. The majority of specimens were comprised of expectorated sputum,
      induced sputum, broncho-alveolar lavage (BAL), and tracheal aspirates. In only
      four patients Pneumocystis carinii (P. carinii) was detected. All the samples
      were produced by broncho-alveolar lavage. Candida spp and Aspergillus spp were
      also identified in a small number of patients. Acid-fast-bacilli were not
      detected in any of the cases under study. There were no sex-related differences
      in distribution. The present prospective study was undertaken in order to
      determine P. carinii infections in human immunodeficiency virus (HIV)
      seropositive and seronegative individuals. Expectorated sputum samples were
      probably the major limiting factor in low positivity for detection of P. carinii
      and study of BAL specimens would be more useful for better results.

PMID- 11289005
TI  - Compostela Valley: a new endemic focus for Capillariasis philippinensis.
AB  - A 20 year old female from Compostela Valley Province in the Philippines,
      presenting with chronic diarrhea, borborygmi, bipedal edema, anorexia and weight
      loss was seen at Davao Regional Hospital. Her stool specimen, suspected by a
      local medical technologist to have Capillaria philippinensis ova, was forwarded
      to the Diagnostic Parasitology Laboratory of the College of Public Health,
      University of the Philippines Manila. It was examined and found to contain
      Capillaria philippinensis adults, larvae and eggs. Twelve deaths among people
      coming from the same barangay, affected by a similar illness with no definite
      diagnosis except "gastroenteritis" were also reported. These prompted health
      officials to send a team that would investigate the etiology of the disease
      outbreak labeled as a "Mystery Disease". Seventy-two stool samples from
      symptomatic patients were examined. Fifty-three (73.6%) individuals were proven
      to harbor at least one parasite with 16 (22.2%) individuals positive for
      Capillaria philippinensis infection. Ocular inspection, interviews and focus
      group discussions revealed that the people's eating habits are not much different
      from the habits of those from the Ilocos provinces where capillariasis was
      initially described. In both areas, people are fond of eating kinilaw or raw
      fish. They also eat raw shrimps, crabs and snails. Furthermore, the people
      defecate in the field or in the same body of water where they get the fishes,
      shrimps, crabs and snails that they eat, thus completing the life cycle of
      Capillaria philippinensis. Fish-eating birds were likely to have spread this
      parasite to the area. This is the first report of a capillariasis outbreak in
      Compostela Valley Province, and this should alert health authorities to consider
      embarking on serious efforts for developing proficiency of laboratory and
      clinical diagnosis especially in government health facilities where the poor and
      marginalized sectors of society are likely to consult.

PMID- 11289006
TI  - Safety and immunogenicity of Bacillus Calmette-Guerin vaccine in children born to
      HIV-1 infected women.
AB  - This prospective cohort study was conducted to determine the complication of
      Bacillus Calmette-Guerin (BCG) vaccination given to newborn infants born to HIV-1
      seropositive mothers and to compare the tuberculin reaction 9 months after BCG
      vaccination between HIV-1 infected and non infected children. Two hundred and
      twenty-three infants with BCG immunization at birth were examined. No BCG
      complication was noted. Tuberculin skin tests were performed on 126 children
      (56.5%). Eleven of them were excluded because of failure to have skin tests read
      at 48 hours. Of the 115 infants enrolled to this study, 15 (13%) had no BCG scar
      and 50 (43.5%) had no tuberculin reaction. Twenty-six children were classified as
      group 1 or HIV-1 infected children and 89 children were group 2 or HIV-1 non
      infected. Group 1 children had a smaller tuberculin skin response (X+SD) than
      group 2 (1.15 +/- 2.82 vs 4.64 +/- 4.29 mm; p < 0.0001). Mean weight + SD of
      group 1 children was also significantly less than those in group 2 (8,013 +/- 741
      vs 8,540 +/- 984 g; p < 0.05). The proportion of children with non reactivity to
      the tuberculin test, a negative tuberculin test and no BCG scar in group 1 was
      significantly higher than that in group 2 (76.9% vs 33.7%, 92.3% vs 52.8% and
      36.4% vs 6.7% respectively; p < 0.0001 for all). But, the proportion of non
      reactivity to the tuberculin test in children with or without BCG scar of each
      group was not different (p > 0.05). Positive tuberculin tests were 7.7% and 47.2%
      in group 1 and 2 respectively. None of the children with positive tuberculin
      tests had clinical evidence of tuberculosis. The findings of this study indicate
      that BCG vaccine given to newborn infants of HIV-1 seropositive mothers is safe.
      Although tuberculin skin responses of HIV-1 infected children are less than those
      of HIV-1 non-infected children, it is possible that BCG vaccine might protect
      these children from developing severe tuberculosis.

PMID- 11289007
TI  - A post-marketing surveillance study of a combined diphtheria, tetanus, whole-cell
      pertussis, and hepatitis B vaccine in the Philippines.
AB  - As part of a vaccination program which included about 30,000 children, 1,036
      children were actively followed up to assess the reactogenicity of a combined
      DTPw-HB vaccine (Tritanrix-HB) under routine conditions. Vaccinations were given
      in accordance with the WHO schedule at 6, 10, and 14 weeks of age. Over 98% of
      the study population completed the course of 3 vaccinations. Local and systemic
      reactions to the vaccine were mostly mild and transient, and almost all had
      resolved by 3 days after vaccination. The most common systemic reactions were
      irritability, restlessness, and unusual crying. Only 3 infants had fever of > or
      = 40 degrees C after any vaccination. No serious adverse events were reported
      during the study. Most health workers taking part in the study thought that
      combined vaccines were better than separate vaccinations. Overall, these results
      show that the combined DTPw-HB vaccine used in the study was well tolerated and
      accepted under conditions of normal use.

PMID- 11289008
TI  - Multiple mutations in the rpoB gene of Mycobacterium leprae strains from leprosy
      patients in Thailand.
AB  - A new finding is reported of multiple mutations in the rpoB gene of 9
      Mycobacterium leprae strains from leprosy patients in Thailand, who did not
      respond to therapy even when rifampicin, the main drug in multi-drug therapy was
      used. By means of sequence analysis of 9 Thai M. leprae strains, various
      mutations in 289 bps of the rpoB gene revealed forms of mutation never before
      described, such as multiple mutations (ie, mutation at two, three, six, seven,
      eight and nine positions in the rpoB gene), most of which were point-mutation
      substitutions (a few of which were silent), and some insertions. This
      investigation demonstrates that mutation in the rpoB gene of M. leprae strains
      from Thailand involves more variety than previously reported for rpoB mutation
      patterns in rifampicin resistance M. leprae strains.

PMID- 11289009
TI  - Evaluation of susceptibility status of invasive pneumococcal isolates to various
      antibiotics and risk factors associated with invasive penicillin-nonsusceptible
      pneumococcal infection: Bangkok 1997-1998.
AB  - The antibiotic susceptibility pattern of Streptococcus pneumoniae isolated from
      specimens of invasive infections was examined at Siriraj Hospital, a tertiary
      care center in Bangkok, during December 1996 April 1998. The percentage of S.
      pneumoniae isolates intermediate and resistant to various antibiotics were:
      penicillin, 25% and 21%; amoxicillin-clavulanate, 24% and 0%; cefuroxime, 6% and
      36%; cefotaxime, 6% and 1.4%; ceftibuten, 5% and 42%; imipenem 22% and 0%; co
      trimoxazole, 6% and 41%; chloramphenicol, 2% and 26%; erythromycin, 12% and 16%;
      azithromycin, 0% and 30%; and roxithromycin 0% and 33%. Most of the penicillin
      nonsusceptible S. pneumoniae (PNSP) were also nonsusceptible to other antibiotics
      except cefotaxime, and imipenem. The isolates from respiratory specimens have a
      higher rate of resistance to all antimicrobial agents with a significant rise in
      MIC50 of beta-lactam antibiotics. There was no difference in the outcome of
      infections caused by penicillin-susceptible and -nonsuscetible S. pneumoniae. The
      only identifiable risk factor associated with PNSP infection was prior use of
      antibiotic within 3 weeks.

PMID- 11289010
TI  - Community acquired-bacterial meningitis in adults.
AB  - We reviewed the charts of all patients > or = 15 years of age or older in whom
      community acquired-bacterial meningitis was diagnosed at Srinagarind Hospital,
      Khon Kaen, Thailand from 1984 through 1998. Eighty-five patients were included in
      this study. The clinical manifestation was acute meningitis with CSF neutrophilic
      pleocytosis and low glucose content. Gram's staining of CSF was positive in 79%.
      The most common pathogens were Streptococcus pneumoniae (28%) and Escherichia
      coli (14%) respectively. The overall mortality was 34%.

PMID- 11289011
TI  - Rapid diagnosis of tuberculous pleural effusion using polymerase chain reaction.
AB  - Between October 1998 and September 1999, 98 patients with symptomatic exudative
      lymphocytic pleural effusion were enrolled in our study to evaluate the
      diagnostic sensitivity of polymerase chain reaction (PCR) assay. The mean age was
      53.3 years ranging from 18 to 78 years. There were 61 men and 37 women. Pleural
      fluid was sent for gram staining, AFB staining, aerobic culture, culture of
      Mycobacterium tuberculosis on LJ media, and cytology. Additional fluid was used
      for a PCR-assay of the 16 S-23 S rRNA gene spacer sequences and for a nested PCR
      of the 16 S rRNA gene as a blind control. In cases of free-flow pleural tapping,
      histopathological analysis was done on three pleural biopsies. Overall etiologies
      comprised malignancy 53.1%, tuberculosis 36.7%, lymphoma 2.0% and chronic
      nonspecific inflammation 8.2%. The sensitivity and specificity of AFB-staining
      were 6% and 79%, respectively; while cultures on LJ media were 17% and 100%,
      respectively. The sensitivity of the PCR-assay was 50% (95% CI: 40 to 60%) and
      the specificity was 61% (95 CI: 52 to 71%). When PCR was nested, the sensitivity
      was 72% (95% CI: 63 to 81%) and specificity was 53% (95% CI: 43 to 63%). Two
      thirds (26 of 36) of tuberculous pleural effusion cases underwent pleural biopsy,
      and 62% were diagnosed by histopathology. There were no complications from
      thoracocentesis or pleural biopsy in any of the patients. We concluded that PCR
      assay was more sensitive than AFB staining and mycobacteria culture for diagnosis
      tuberculous pleural effusion but its specificity was quite low.

PMID- 11289012
TI  - Introduction of a rapid dipstick assay for the detection of Leptospira-specific
      immunoglobulin m antibodies in the laboratory diagnosis of leptospirosis in a
      hospital in Makassar, Indonesia.
AB  - An easy, rapid and robust dipstick assay for detection of leptospira-specific
      immunoglobulin M (IgM) antibodies was evaluated on 403 patients admitted for
      hospitalization because of fever. The clinical symptoms and signs of 35 patients
      were consistent with leptospirosis. The final diagnosis for the remaining
      patients was as follows: 136 with typhoid fever, 82 with hepatitis, 74 with
      malaria, 48 with infections of the respiratory tract, and 20 with fever of
      unknown origin. The clinical diagnosis of leptospirosis was confirmed for 24
      (68.6%) patients by the combined results of the microscopic agglutination test
      (MAT), the reference test for leptospirosis, and of IgM ELISA, a standard
      laboratory test for the serodiagnosis of leptospirosis. In addition, serum
      specimens from 8 (2.2%) patients with a final clinical diagnosis other than
      leptospirosis were found to be positive in MAT and/or IgM ELISA. Compared with
      the results of MAT and IgM ELISA a sensitivity of 91.6% and specificity of 93.6%
      was calculated for the dipstick assay. Most of the serum samples from the
      laboratory confirmed patients gave a moderate to strong staining intensity of the
      antigen band of the dipstick and were easy to read. The results demonstrate that
      the dipstick assay is convenient to use and allows the rapid and accurate
      confirmation of patients with clinical suspicion of leptospirosis in areas where
      the disease is endemic.

PMID- 11289013
TI  - Causes of fever in children with first febrile seizures: how common are human
      herpesvirus-6 and dengue virus infections?
AB  - This study was conducted to evaluate the etiologies of pyrexia in children with
      first febrile seizures using a prospectively recorded medical protocol, bacterial
      culture, and serologic tests for human herpesvirus-6 (HHV-6), dengue virus and
      Japanese B encephalitis (JE) virus. Of 82 children with first febrile seizures,
      who were between 3 months and 3 years old and had been admitted to Bhumibol
      Adulyadej Hospital between January 1997 and December 1998, 41 were boys and 41
      were girls, with a mean age of 14.7 months. The average maximal body temperature
      was 39.7 degrees C. Approximately 70% of the children developed seizures on the
      first day of fever and the duration of the seizures varied from 1 to 30 minutes.
      In addition to fever and seizure, common symptoms and signs included coryza,
      diarrhea, vomiting, inflamed tympanic membranes and rash. The causes of fever
      documented upon discharge were, in order of frequency, upper respiratory tract
      infection, nonspecific febrile illness, diarrhea, urinary tract infection, viral
      infection, pneumonia, herpangina, measles, pneumococcal bacteremia and dengue
      fever. Serologic tests for HHV-6 IgM were positive in seven children (8.5%), and
      serologic tests for dengue and JE viruses were negative in all cases.

PMID- 11289014
TI  - IgM-capture ELISA of serum samples collected from Filipino dengue patients.
AB  - Viral antigens for 4 dengue serotypes were produced in C6/36 Aedes albopictus
      cells. These were used as assay antigens for IgM-capture ELISA to detect IgM
      antibodies in sera of dengue patients from 3 hospitals in Metro Manila,
      Philippines. A total of 378 serum samples came from National Children's Hospital
      (NCH), San Lazaro Hospital (SLH), and St Luke's Medical Center (SLMC), from
      January to November 1995. Three hundred and four (304) out of 378 serum samples,
      or 80.42% showed positive IgM ELISA titer against at least one of the 4 assay
      antigens. Dengue type 4 (D4) antigen detected antibodies in 61.90% (234/378) of
      these serum samples, whereas type 1 (D1), type 3 (D3), and type 2 (D2) had
      detection rates of 60.05% (227/378), 50.79% (192/378) and 49.47% (187/378)
      respectively. Although the results show that both D1 and D4 are the most
      effective antigens in identifying dengue infections for this batch of samples,
      the use of a cocktail of antigens is still recommended. The results of this study
      are the basis for the IgM-capture ELISA protocol presently applied for the
      laboratory confirmation of dengue cases in the Philippines.

PMID- 11289015
TI  - Hepatitis B and C virus infection among adult women in Jilin Province, China: an
      urban-rural comparison in prevalence of infection markers.
AB  - Twin seroepidemiological surveys on prevalence of hepatitis B and C virus (HBV
      and HCV, respectively) infection were conducted on 100 adult women in total, 50
      each in the provincial capital of Changchun and in a farming village in the
      vicinity in Jilin Province, northeast China. Positivity to three markers on HBV
      (ie HBsAg+, anti-HBs+, and anti-HBc+) was examined by RIA methods, and to one on
      HCV (anti-HCV+) by EIA. The results were evaluated in combination with two
      foregoing studies in Shandong and Shaanxi Provinces, and with special reference
      to possible urban-rural differences in prevalence. The prevalence of HBsAg+ cases
      was rather low (ie 9% when two groups were combined), but that of anti-HBs+ and
      anti-HBc+ cases was high, being 50% and 45%, respectively. Thus, the rate of HBV+
      cases was 62%. The rate for HCV+ cases was 3%. The comparison of the prevalence
      between the city group and the village group showed that the rates for anti-HBs+
      and HBV+ were significantly or marginally higher in the former group than in the
      latter, respectively. The HCV+ prevalence rate for the city group (4%) also
      tended to be higher than the corresponding rates for the village group (2%),
      although the difference was statistically insignificant. When evaluated together
      with the observation in Shandong and Shaanxi Provinces, it appears possible to
      generalize that the HBV infection prevalence is not higher and probably lower in
      rural areas than in urban areas, and that such may also be the case for the HCV
      infection prevalence.

PMID- 11289016
TI  - Clostridium difficile infections in HIV-positive patients.
AB  - The prevalence of Clostridium difficile infections in HIV-positive patients with
      regard to the presence of its enterotoxin was investigated. Enzyme immunoassay
      (EIA, Meridian Diagnostic Inc) was used for the detection of C. difficile
      enterotoxin in stool specimens collected from 201 HIV-positive and 271 HIV
      negative diarrheal patients. Culture was performed on cycloserine cefoxitin
      fructose agar. Chromosomal DNA types of C. difficile isolates were determined by
      pulsed-field gel electrophoresis (PFGE). In the HIV-positive group, C. difficile
      enterotoxin was found in 58.8% and 12.6% of diarrheal and non-diarrheal patients,
      repectively, whereas this toxin was found in 36.5% of HIV-negative-diarrheal
      patients. However, 13.6% of stool samples were negative by toxin assay, but were
      positive for C. difficile by culture and latex agglutination test. Among 11
      isolates from both HIV-positive and HIV-negative patients, 6 patterns of PFGE
      type were observed: A, B, C, D, E and F.

PMID- 11289017
TI  - Peritonitis complicating acute peritoneal dialysis in Northeast Malaysia.
AB  - A prospective observational study examing the incidence, predisposing factors and
      microbiological aspects of peritonitis complicating acute intermittent peritoneal
      dialysis (IPD) was performed in Hospital Universiti Sains Malaysia, a referral
      hospital situated in Northeast Malaysia. Over a 7- month period, a total of 126
      acute IPD treatments were included involving 69 patients. The majority of
      patients suffered from chronic or end stage renal failure (92.7%) and nearly half
      (47.8%) have underlying diabetes mellitus. Peritonitis occured in 25 treatment
      sessions giving a frequency of 19.8% of procedures performed. The mean interval
      between starting dialysis and the first sign of peritonitis was 3.5 days, with
      12% of peritonitis occuring before day 3 of treatment. Frequent catheter
      manipulation and/or leakages were identified as significant predisposing factors
      for peritonitis and the risk of peritonitis was increased with longer duration of
      IPD. Gram-negative infections were seen twice more commonly than gram-positive
      infections. We recommend the use of cloxacillin in combination with either an
      aminoglycoside or a cephalosporin as empirical antibiotic coverage until culture
      reports are available.

PMID- 11289018
TI  - Illness experience and coping with gynecological cancer among northeast Thai
      female patients.
AB  - This quantitative and qualitative study describes the illness experience and the
      coping mechanisms of cervical cancer patients. Interviews were performed with 208
      cervical cancer patients to determine their health seeking behavior and illness
      beliefs. Most began their treatment at local health services and district
      hospitals, and sought treatment in up to four different places before coming to
      the University Hospital. Most of the respondents were not sure about the cause of
      cervical cancer, and waited to see their symptoms before seeking treatment. Most
      perceived their condition as at an early stage. The qualitative research
      consisted of interviews with 79 selected patients and identified stigmatization
      from family and community members, problems with sexuality, and varied belief in
      meaning and causation of the disease. Many of the problems faced were coped with
      because of support from husbands, family and the community. It is recommended
      that better recording of patient data would allow a better follow-up service, and
      improved information for relatives would help them to understand the patient's
      problems, with both of these contributing to a better recovery environment for
      patients.

PMID- 11289019
TI  - Management model of community participative rabies vaccine fund.
AB  - The objective of this study was to set up a management model of a Rabies Vaccine
      Fund by using community participation. It was a Participatory Action Research-PAR
      (Research and Development) during January-December 1999. The target population
      were the Local Administrative Organization (LAO) committee, community leaders and
      village health volunteers. The research instrument was the focus group discussion
      purposively set. The result showed that the Rabies Vaccine Fund was successful,
      sustainable with no rabies case and the fund increased. The management model of
      Rabies Vaccine Fund consists of the fund committee, community participation in
      fund raising, delegation of work, fund regulation, animal vector registration and
      immunization, and provision of health education through village cable line. The
      recommendation is that promotion of this type of Rabies Vaccine Fund should be
      one alternative of a rabies protection and control program.

PMID- 11289020
TI  - HLA class II alleles in Japanese patients with non-Hodgkin's lymphoma.
AB  - The distribution of HLA-DRB1 alleles and DQB1 alleles in 30 Japanese patients
      with non-Hodgkin's lymphoma (NHL) was analyzed using polymerase chain reaction
      with the sequence-specific primer (PCR-SSP) method, and the association between
      the disease and the presence of certain HLA class II alleles was investigated.
      The frequencies of HLA-DRB1*0803, DRB1*0802 and DRB1*1502 were increased while
      those of DRB1*1501 and DRB1*0405 were decreased. On the other hand, the incidence
      of HLA-DQB1 alleles was similar to that in the normal population. However, none
      of these HLA class II alleles showed significant positive or negative
      associations with NHL. In addition, when allele frequencies of NHL Japanese
      patients were compared to Thai patients, only DRB1*0803 was significantly
      increased in Japanese patients. These results indicate that DRB1*0803 may not
      contribute to NHL susceptibility in the Japanese population. However, further
      studies with larger numbers of NHL Japanese patients are needed to confirm our
      preliminary findings.

PMID- 11289021
TI  - Prevention and control of thalassemia in Ramathibodi Hospital, Thailand.
AB  - Eight thousand seven hundred and thirty-six pregnant women were screened for
      thalassemia and hemoglobinopathies by mean corpuscular volume less than 80
      femtolitres (fl). Three thousand six hundred and seventy women (42%) were MCV
      less than 80 fl. In this group there were 2,390 women (70%) who had positive Hb
      typing by high performance liquid chromatography (HPLC) such as beta-thalassemia
      major, beta-thalassemia hemoglobin E disease, beta-thalassemia trait,
      heterozygous and homozygous hemoglobin E, alpha-thalassemia-1 trait and
      hemoglobin H disease and 77% of their partners came and had hemoglobin typing
      done. Seventy-five couples at risk for having severely affected thalassemia
      fetuses were detected from this screening program. Prenatal diagnosis was
      performed in 58 couples (77.3%). Eight affected fetuses were detected. All
      pregnancies with affected fetuses except one with beta-thalassemia/HbE were
      terminated. There were 3 fetal losses (6%) as the result of prenatal diagnosis
      procedure.

PMID- 11289022
TI  - Establishing gas chromatography-mass spectrometry to diagnose organic acidemias
      in Thailand.
AB  - Disorders of organic acid metabolism are a group of disorders which has long been
      ignored by majority of Thai physicians. Part of this is due to lack of
      laboratories in Thailand to verify the diagnosis of the disorders. We have
      recently developed a technique to qualitatively analyze organic acids utilizing
      Gas Chromatography-Mass Spectrometry (GC-MS). Eight patients in four families
      were successfully identified as having organic acidemias (OA) by this method. Two
      families had methylmalonic acidemia, one had propionic acidemia, and the other
      had 3-methylcrotonyl CoA carboxylase deficiency. To our knowledge, this is the
      first laboratory in Thailand being able to use GC-MS to diagnose OA. Availability
      of a laboratory in Thailand and affordability of the test are expected to result
      in earlier diagnosis and identification of more cases of OA in Southeast Asian
      countries. Consequently, prompt and proper treatment can be anticipated which
      should lead to better prognosis for patients with this group of disorder.

PMID- 11289023
TI  - Prevalence of infectious diseases and drug abuse among Bangladeshi workers.
AB  - Individuals seeking jobs abroad need health fitness certificates before entering
      into those countries. Medical screening of 43,213 Bangladeshi job seekers (M/F:
      42,290/923) was carried out in our reference center during the period August,
      1994 to May, 1996. Albeit male predominance, they represented middle and lower
      middle socio-economic class of the population from all over the country. All were
      young adults (age: 27.05+/-3.56 years; mean+/-SD) applying for job visas to
      different Asian countries. Physical examination and laboratory investigations
      including markers for several infectious diseases and drugs of abuse were carried
      out as required by countries recruiting the workers. Serological tests revealed
      that 1,884 (4.4%) of individuals were positive for hepatitis B surface antigen
      (HBsAg), 737 (1.7%) for Treponema pallidum hemagglutination (TPHA) and only 83
      (0.2%) for antibody to human immunodeficiency virus (anti-HIV). However, we could
      not confirm any case of infection with HIV. Chest X-ray suggestive of pulmonary
      tuberculosis was found in 162 (0.4%) and on blood film, malarial parasites could
      be observed only in 4 cases. Their urine analysis revealed the presence of
      opiates or cannabinoids in 471 (1.1%) individuals. HBsAg-positive cases (p =
      0.003) and abuse of opiates (p = 0.024) or cannabinoids (p = 0.002) were
      significantly higher among males. TPHA reactivity and chest X-ray suggestive of
      tuberculosis were found to be higher among opiates (p = 0.002 and 0.027) and
      cannabinoids (p = 0.000 for both) abused as well as with increasing age (p =
      0.000). These results may represent a cross-sectional view of the prevalence of
      different infectious diseases and abuse of drugs among the young adult population
      of Bangladesh.

PMID- 11289024
TI  - Respiratory health of rice millers in Kelantan, Malaysia.
AB  - A cross sectional study was carried out to evaluate the effect of rice husk dust
      in rice millers in Malaysia. Altogether 69 workers participated in this study.
      They were interviewed using standardized questionnaires and lung function tests
      were performed. Chest tightness was among the common symptoms (34.9%) complained
      by workers. Age, duration of employment and smoking status were among the factors
      associated with respiratory symptoms (p < 0.01). Lung function tests revealed
      some degree of impairment compared to the healthy population.

PMID- 11289025
TI  - Dietary fluoride intake of children aged 3-7 years in remote areas of Thailand.
AB  - The objectives of this study were to measure dietary fluoride intake in children
      aged 3-7 years, to correlate dietary fluoride and fluoride content in water for
      use in schools and to estimate fluoride gained from the daily diet. Fifty food
      samples were collected in 45 schools under the jurisdiction of the Border Patrol
      Police Department. The schools were sampled by multiple stratified cluster random
      sampling. The food samples were weighed, then measured for fluoride content by a
      microdiffusion method. Statistical analysis was conducted using the Kruskal
      Wallis test. Dietary fluoride in each age group was compared by Student's t test.
      Analysis for the relationship between dietary fluoride and fluoride content in
      water was done using Kendall's tau-b. Our results showed that the mean of dietary
      fluoride in lunch was 0.08 +/- 0.1 ppm. There were no differences when comparing
      dietary fluoride between different regions of Thailand (p = 0.07). No correlation
      was found between dietary fluoride and fluoride content in water used in
      different schools (r(tau) = 0.017, p = 0.85). The daily dietary fluoride intake
      in children aged 3-6 years was 0.002-0.004 mgF/kg bw/day, in children aged 7
      years was 0.003-0.004 mgF/kg bw/day in boys and 0.002-0.004 mgF/kg bw/day in
      girls.

PMID- 11289026
TI  - Fluoride analysis of human milk in remote areas of Thailand.
AB  - The objective of this study was to measure the fluoride content in human milk
      collected from mothers living in remote areas of Thailand and to correlate it
      with fluoride concentrations in drinking water and water for domestic use. Four
      to five ml of breast milk were sampled from mothers living in villages where
      schools under the jurisdiction of the Department of Border Patrol Police were
      located. The schools were sampled by Multiple Stratified Cluster Random Sampling.
      Fluoride was determined by microdiffusion method. Statistical analysis were made
      by ANOVA and LSD test. Correlation between fluoride content in milk and water was
      assessed by Kendall's tau-b. The mean fluoride concentration in breast milk was
      0.017+/-0.02 ppm. There was no difference in breast milk fluoride concentration
      between regions (p=0.6). No correlation was found between breast milk fluoride
      content and fluoride concentrations in either drinking water or water for
      domestic use (r(tau) = -0.09, p = 0.32, r(tau) = -0.04, p = 0.65 respectively).

PMID- 11289027
TI  - Urine trans,trans-muconic acid determination for monitoring of benzene exposure
      in mechanics.
AB  - Benzene is an important carcinogenic substance used in many industrial processes.
      Inhalation of this substance can cause both acute and chronic toxicity. In this
      study, monitoring of benzene exposure by high-performance liquid chromatography
      for urine trans,trans-muconic acid (ttMA) determination in 94 subjects, (49
      control subjects and 45 mechanics) was performed. The mean urine ttMA level in
      the control group was 0.116 +/- 0.027 mg/g creatinine. The mean urine ttMA level
      in the mechanics group was 0.280 +/- 0.131 mg/g creatinine. There was a
      significant difference between the groups (p < 0.05). Based on this study, we
      recommend the use of urine ttMA determination for monitoring of benzene exposure
      in high risk workers.

PMID- 11289028
TI  - Pharmaceutical sector in transition--a cross sectional study in Vietnam.
AB  - Increasing efforts are being made to improve pharmaceutical sector performance in
      low- and middle-income countries. An essential tool for such work is an objective
      and standard method of assessment which can be used to promote evidenced based
      National Drug Policy development and implementation. The average drug expenditure
      per capita has steadily increased in Vietnam and at the time of this study a
      National Drug Policy was being developed. This study assessed the Vietnamese
      pharmaceutical sector 1991-1994, focusing on the standard of the drug quality
      control system, availability of drugs and rational use of essential drugs in the
      private and public sectors by means of standardised indicators. The results from
      this study show that the quality control system is impaired and does not have
      capacity to quality control all drugs on the market. The availability of
      essential drugs is good whereas essential drugs are poorly prescribed, injections
      common and there is a high average number of drugs per prescription, both in the
      public and private sectors. Violations are common and enforcement of regulations
      weak. On top of this there is an active commercial advertising and marketing of
      drugs. These findings identify priorities for action to improve the present
      situation where the development and implementation of the Vietnamese National
      Drug Policy will be of major importance.

PMID- 11289029
TI  - Community-based self-reported symptoms of antepartum morbidities; the health
      burden and care-seeking patterns of rural Bangladeshi women.
AB  - In Bangladesh there is a dearth on information relating to complications during
      pregnancy. We followed up 1,019 pregnant women in rural Bangladesh sampled from
      all the 4 old administrative divisions of the country. Trained female
      interviewers visited households of the pregnant women at four-week intervals and
      interviewed them for their current pregnancy-related complications. Out of a
      total of 3,812 antepartum visits the percentage of reported symptoms of bleeding,
      fits and convulsions, excessive vomiting, fever >3 days, urinary problems,
      palpitations and symptomatic anemia were 0.3, 0.7, 1.4, 4.0, 26.8, 46.5 and 78.3
      respectively. Morbidities were considered to cause a health burden if they
      imposed constraints in daily activities of the pregnant women and they were
      weighted according to intensity of the constraint. For each morbidity, the mean
      intensity of burden per episode and the population burden per 1,000 person months
      of observation of all the women were calculated. For common sustaining
      morbidities like symptomatic anemia and urinary problems the population burden
      was much heavier than that for more serious but rare morbidities like bleeding
      and convulsions. Among the visits in which the women had any symptoms, the
      percentages of care-seeking for less frequently reported morbidities such as fits
      and convulsions, bleeding, fever >3 days, excessive vomiting were about 74, 50,
      34 and 33% respectively, whereas those for more commonly reported complications
      such as urinary problems, symptomatic anemia and palpitations were less than 20%.
      Care for these morbidities was mostly sought from untrained providers.

PMID- 11289030
TI  - Improvement of growth of Plasmodium falciparum fresh clinical isolates by using
      an established serum-free medium, GIT.
AB  - In the present study, we have tried to establish continuous cultures of fresh
      clinical isolates of P. falciparum by using a serum-free medium, GIT. To examine
      the ability of GIT to support the parasite growth, the growth of various P.
      falciparum isolates including two laboratory strains of P. falciparum, FCR3 and
      K1 was compared in both of GIT and RPMI 1640 medium supplemented by 10% human
      serum (RPMI-HS). Growth rates of various P. falciparum expressed as fold
      increases were compared in GIT and RPMI-HS, and the maximum growth rates of P.
      falciparum were 72 in GIT and 35 in RPMI-HS during the culture for 8 days. Growth
      rate of the clinical isolates varied individually in both culture media, with
      average growth rates of parasites being 15.9 in GIT and 8.8 in RPMI-HS,
      respectively (not significant). Growth rates of FCR3 and K1 strains were 28.0 and
      6.6 in GIT, and 10 and 7.5 in RPMI-HS. After 30 days culture of P. falciparum in
      GIT, 9 of 12 clinical isolates still continuously propagated but other three
      isolates disappeared. Despite variation of the P. falciparum isolates in their
      abilities to multiply in GIT, our experiments suggested that GIT is useful for
      culture of fresh clinical isolates of P. falciparum that are derived from
      geographically distinct areas as well as laboratory strains used commonly in
      laboratory research.

PMID- 11289031
TI  - A study on attitude towards blood donation among people in a rural district,
      Thailand.
AB  - Blood and blood components are important in many situations. At present, there is
      only a donation system for blood banks to get blood in Thailand. Although the
      blood bank process has been founded in Thailand for many years, there is still an
      insufficient amount of blood for use. There are misguided attitudes on blood
      donation among the people in the rural areas. This study has been designed as a
      cross-sectional descriptive study to study attitude towards blood donation among
      the people in Bang Sapan District, Prachuab Kiri Khan Province, Thailand. Data
      from self-administered questionnaires were collected and statistical analysis was
      performed. We found that people in that area had a rather good attitude but this
      was still found in less than 50%. We found the attitude of the subjects only
      significantly correlated with the level of education. We concluded that improving
      the people's attitude on blood donation is important. We suggest that every blood
      bank should design a program for providing knowledge in order to improve the
      attitude of the people in that area. We also suggest that knowledge on blood
      donation should be repeatedly taught at any education level including the school
      system. This study can provided preliminary results for other studies.

PMID- 11289032
TI  - Circulating ghrelin levels are decreased in human obesity.
AB  - Ghrelin is a novel endogenous natural ligand for the growth hormone (GH)
      secretagogue receptor that has recently been isolated from the rat stomach.
      Ghrelin administration stimulates GH secretion but also causes weight gain by
      increasing food intake and reducing fat utilization in rodents. To investigate
      the possible involvement of ghrelin in the pathogenesis of human obesity, we
      measured body composition (by dual X-ray absorption) as well as fasting plasma
      ghrelin concentrations (radioimmunoassay) in 15 Caucasians (8 men and 7 women,
      31+/-9 years of age, 92+/-24 kg body wt, and 29+/-10% body fat, mean +/- SD) and
      15 Pima Indians (8 men and 7 women, 33+/-5 years of age, 97+/-29 kg body wt, and
      30+/-8% body fat). Fasting plasma ghrelin was negatively correlated with percent
      body fat (r = -0.45; P = 0.01), fasting insulin (r = -0.45; P = 0.01) and leptin
      (r = -0.38; P = 0.03) concentrations. Plasma ghrelin concentration was decreased
      in obese Caucasians as compared with lean Caucasians (P < 0.01). Also, fasting
      plasma ghrelin was lower in Pima Indians, a population with a very high
      prevalence of obesity, compared with Caucasians (87+/-28 vs. 129+/-34 fmol/ml; P
      < 0.01). This result did not change after adjustment for fasting plasma insulin
      concentration. There was no correlation between fasting plasma ghrelin and
      height. Prospective clinical studies are now needed to establish the role of
      ghrelin in the pathogenesis of human obesity.

PMID- 11289033
TI  - Clinical outcomes and insulin secretion after islet transplantation with the
      Edmonton protocol.
AB  - Islet transplantation offers the prospect of good glycemic control without major
      surgical risks. After our initial report of successful islet transplantation, we
      now provide further data on 12 type 1 diabetic patients with brittle diabetes or
      problems with hypoglycemia previous to 1 November 2000. Details of metabolic
      control, acute complications associated with islet transplantation, and long-term
      complications related to immunosuppression therapy and diabetes were noted.
      Insulin secretion, both acute and over 30 min, was determined after intravenous
      glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5
      17.4), and the longest was 20 months. Glucose control was stable, with
      pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9
      and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with
      posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P <
      0.006). All patients have sustained insulin production, as evidenced by the most
      current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25
      nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from
      8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four
      patients have normal glucose tolerance, five have impaired glucose tolerance, and
      three have post-islet transplant diabetes (two of whom need oral hypoglycemic
      agents and low-dose insulin (<10 U/day). Three patients had a temporary increase
      in their liver-function tests. One patient had a thrombosis of a peripheral
      branch of the right portal vein, and two of the early patients had bleeding from
      the hepatic needle puncture site; but these technical problems were resolved. Two
      patients had transient vitreous hemorrhages. The two patients with elevated
      creatinine levels pretransplant had a significant increase in serum creatinine in
      the long term, although the mean serum creatinine of the group was unchanged. The
      cholesterol increased in five patients, and lipid-lowering therapy was required
      for three patients. No patient has developed cytomegalovirus infection or
      disease, posttransplant lymphoproliferative disorder, malignancies, or serious
      infection to date. None of the patients have been sensitized to donor antigen. In
      11 of the 12 patients, insulin independence was achieved after 9,000 islet
      equivalents (IEs) per kilogram were transplanted. The acute insulin response and
      the insulin area under the curve (AUC) after IVGTT were consistently maintained
      over time. The insulin AUC from the IVGTT correlated to the number of islets
      transplanted, but more closely correlated when the cold ischemia time was taken
      into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully
      corrected labile type 1 diabetes and problems with hypoglycemia, and our results
      show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are
      provided, insulin independence is usually attained. An elevation of creatinine
      appears to be a contraindication to this immunosuppressive regimen. For the
      subjects who had labile type 1 diabetes that was difficult to control, the risk
      to-benefit ratio is in favor of islet transplantation.

PMID- 11289034
TI  - Control of glycogen synthesis by glucose, glycogen, and insulin in cultured human
      muscle cells.
AB  - A key feature of type 2 diabetes is impairment in the stimulation of glycogen
      synthesis in skeletal muscle by insulin. Glycogen synthesis and the activity of
      the enzyme glycogen synthase (GS) have been studied in human myoblasts in culture
      under a variety of experimental conditions. Incubation in the absence of glucose
      for up to 6 h caused an approximately 50% decrease in glycogen content, which was
      associated with a small decrease in the fractional activity of GS. Subsequent
      reincubation with physiological concentrations of glucose led to a dramatic
      increase in the rate of glycogen synthesis and in the fractional activity of GS,
      an effect which was both time- and glucose concentration-dependent and
      essentially additive with the effects of insulin. This effect was seen only after
      glycogen depletion. Inhibitors of signaling pathways involved in the stimulation
      of glycogen synthesis by insulin were without significant effect on the
      stimulatory action of glucose. These results indicate that at least two distinct
      mechanisms exist to stimulate glycogen synthesis in human muscle: one acting in
      response to insulin and the other acting in response to glucose after glycogen
      depletion, such as that which results from exercise or starvation.

PMID- 11289035
TI  - In normal men, free fatty acids reduce peripheral but not splanchnic glucose
      uptake.
AB  - Raising plasma free fatty acid (FFA) levels reduces muscle glucose uptake, but
      the effect of FFAs on splanchnic glucose uptake, total glucose output, and
      glucose cycling may also be critical to producing lipid-induced glucose
      intolerance. In eight normal volunteers, we measured glucose turnover and cycling
      rates ([2H7]glucose infusion) during a moderately hyperglycemic (7.7 mmol/l)
      hyperinsulinemic clamp, before and after ingestion of a labeled (dideuterated)
      oral glucose load (700 mg/kg). Each test was performed twice, with either a lipid
      or a saline infusion; four subjects also had a third test with a glycerol
      infusion. As shown by similar rates of exogenous glucose appearance, the lipid
      infusion did not reduce first-pass splanchnic glucose uptake (saline 1.48+/-0.18,
      lipid 1.69+/-0.17, and glycerol 1.88+/-0.17 mmol/kg per 180 min; NS), but it
      reduced peripheral glucose uptake by 40% (P < 0.01 vs. both saline and glycerol
      infusions). Before oral ingestion of glucose, total glucose output was similarly
      increased by the lipid and glycerol infusions. Total glucose output was
      significantly increased by FFAs after oral ingestion of glucose (saline 3.68+/
      1.15, glycerol 3.68+/-1.70, and lipid 7.92+/-0.88 micromol x kg(-1) x min(-1); P
      < 0.01 vs. saline and P < 0.05 vs. glycerol). The glucose cycling rate was
      approximately 2.7 micromol x kg(-1) x min(-1) with the three infusions and tended
      to decrease all along the lipid infusion, which argues against a stimulation of
      glucose-6-phosphatase by FFAs. It is concluded that in situations of moderate
      hyperinsulinemia-hyperglycemia, FFAs reduce peripheral but not splanchnic glucose
      uptake. Total glucose output is increased by FFAs, by a mechanism that does not
      seem to involve stimulation of glucose-6-phosphatase.

PMID- 11289036
TI  - Cerulenin mimics effects of leptin on metabolic rate, food intake, and body
      weight independent of the melanocortin system, but unlike leptin, cerulenin fails
      to block neuroendocrine effects of fasting.
AB  - Cerulenin and a related compound, C75, have recently been reported to reduce food
      intake and body weight independent of leptin through a mechanism hypothesized,
      like leptin, to involve hypothalamic nutrition-sensitive neurons. To assess
      whether these inhibitors act through mechanisms similar to mechanisms engaged by
      leptin, ob/ob and Ay (agouti) mice, as well as fed and fasted wild-type mice,
      were treated with cerulenin. Like leptin, cerulenin reduced body weight and food
      intake and increased metabolic rate in ob/ob mice, and cerulenin produced the
      same effects in wild-type mice, whereas lithium chloride, at doses that produce
      conditioned taste aversion, reduced metabolic rate. However, in contrast to
      leptin, cerulenin did not prevent effects of fasting on plasma corticosterone or
      hypothalamic levels of neuropeptide Y, agouti-related peptide, pro
      opiomelanocortin, or cocaine- and amphetamine-related peptide mRNA. Also, in
      contrast to leptin, cerulenin was highly effective to reduce body weight in Ay
      mice, in which obesity is caused by blockade of the melanocortin receptor. These
      data demonstrate that cerulenin produces metabolic effects similar to effects of
      leptin, but through mechanisms that are independent of, or down-stream from, both
      leptin and melanocortin receptors.

PMID- 11289037
TI  - Rat small intestine is an insulin-sensitive gluconeogenic organ.
AB  - At variance with the current view that only liver and kidney are gluconeogenic
      organs, because both are the only tissues to express glucose-6-phosphatase
      (Glc6Pase), we have recently demonstrated that the Glc6Pase gene is expressed in
      the small intestine in rats and humans and that it is induced in insulinopenic
      states such as fasting and diabetes. We used a combination of arteriovenous
      balance and isotopic techniques, reverse transcription-polymerase chain reaction,
      Northern blot analysis, and enzymatic activity assays. We report that rat small
      intestine can release neosynthesized glucose in mesenteric blood in
      insulinopenia, contributing 20-25% of total endogenous glucose production. Like
      liver glucose production, small intestine glucose production is acutely
      suppressed by insulin infusion. In the small intestine, glutamine and, to a much
      lesser extent, glycerol are the precursors of glucose, whereas alanine and
      lactate are the main precursors in liver. Accounting for these metabolic fluxes:
      1) the phosphoenolpyruvate carboxykinase gene (required for the utilization of
      glutamine) is strongly induced at the mRNA and enzyme levels in insulinopenia; 2)
      the glycerokinase gene is expressed, but not induced; 3) the pyruvate carboxylase
      gene (required for the utilization of alanine and lactate) is repressed by 80% at
      the enzyme level in insulinopenia. These studies identify small intestine as a
      new insulin-sensitive tissue and a third gluconeogenic organ, possibly involved
      in the pathophysiology of diabetes.

PMID- 11289038
TI  - Assessment of postabsorptive renal glucose metabolism in humans with multiple
      glucose tracers.
AB  - The contribution of the kidneys to postabsorptive endogenous glucose production
      is a matter of controversy. To assess whether this could relate to the use of
      various isotopical methods with different analytical performance capabilities, we
      measured glucose kinetics in 12 healthy subjects. Blood samples were taken from
      the femoral artery and the renal vein after 4 h of [6,6-2H2]glucose infusion (for
      gas chromatography [GC]/mass spectrometry [MS] analysis), and renal plasma flow
      was determined with paraaminohippurate. In addition, six subjects received
      uniformly labeled [13C]glucose (for GC/combustion/isotope ratio MS [IRMS]) and [3
      3H]glucose (for counting of radioactive disintegrations). Arterial glucose
      concentrations (means +/- SD) were 4.2+/-0.1 mmol/l, and endogenous glucose
      production rates using [2H2]glucose were 2.2+/-0.1 mg x kg(-1) x min(-1) or 818+/
      50 micromol/min. Dilution of [2H2]glucose across the kidney was 0.79+/-1.32%, and
      renal glucose production (RGP) rates were 27+/-72 micromol/min. In the six
      subjects receiving additional tracers, dilutions across the kidney were 2.83+/
      0.72 and 0.54+/-1.20 (for [U-13C]glucose and [3-3H]glucose, respectively, the
      dilution with [U-13C] being higher than that with [2H2] (P = 0.007).
      Corresponding RGP values were 144+/-39 and 43+/-76 micromol/min for [U-13C] and
      [3-3H], respectively. In conclusion, we found that the highly sensitive [U-13C]
      GC/Combustion/IRMS technique showed consistent dilution of label across the
      kidney, whereas the less sensitive techniques gave some negative values and
      smaller RGP rates. Thus, depending on which technique is being used, a fivefold
      difference in calculated RGP values may be encountered. The methodological
      variability of our data suggests that extrapolation from regional renal
      measurements to the whole-body level should be perfumed with caution.

PMID- 11289039
TI  - Autoantibody response to CD38 in Caucasian patients with type 1 and type 2
      diabetes: immunological and genetic characterization.
AB  - Insulin secretion is one of the functions mediated by CD38, a nonlineage
      pleiotropic cell surface receptor. The molecule is the target of an autoimmune
      response, because serum autoantibodies (aAbs) to CD38 have been detected in
      diabetic patients. In the healthy Caucasian population, the CD38 gene is bi
      allelic (86% CD38*B and 14% CD38*A), whereas an Arg140Trp mutation has been
      identified in Japanese diabetic patients. We investigated the relationship
      between CD38 and diabetes in Caucasian patients by characterizing anti-CD38 aAbs
      in terms of prevalence and function (agonistic/nonagonistic activity) and by
      exploring the potential influence of the CD38 genetic background. A novel
      enzymatic immunoassay, using recombinant soluble CD38 as the target antigen, was
      developed for the analysis of anti-CD38 aAb titers. Sera from 19.15% of type 1
      and 16.67% of type 2 diabetic patients were positive. The majority of anti-CD38
      aAbs (57.14%) displayed agonistic properties, i.e., they demonstrated the
      capability to trigger Ca2+ release in lymphocytic cell lines. In agreement with
      these functional features, the presence of anti-CD38 aAbs in type 2 diabetic
      patients was associated with significantly higher levels of fasting plasma C
      peptide and insulin, as compared with anti-CD38-counterparts. No diabetic subject
      carrying the Arg140Trp mutation and no preferential association between diabetes
      or aAb status and the CD38*A allele was found in the study population. These
      results show the significance of anti-CD38 aAbs as a new diagnostic marker of
      beta-cell autoimmunity in diabetes. Moreover, the prevalent agonistic activity of
      these aAbs suggests that they could mediate relevant effects on target cells by
      means of Ca2+ mobilization.

PMID- 11289040
TI  - Development and function of diabetogenic T-cells in B-cell-deficient nonobese
      diabetic mice.
AB  - Insulin-dependent diabetes (type 1 diabetes) in the NOD mouse is a T-cell
      mediated autoimmune disease. However, B-cells may also play a critical role in
      disease pathogenesis, as genetically B-cell-deficient NOD mice (NOD.microMT) have
      been shown to be protected from type 1 diabetes and to display reduced responses
      to certain islet autoantigens. To examine the requirements for B-cells in the
      development of type 1 diabetes, we generated a B-cell-naive T-cell repertoire by
      transplantation of NOD fetal thymuses (FTs) into NOD.scid recipients.
      Surprisingly, these FT-derived NOD T-cells were diabetogenic in 36% of NOD.scid
      recipients, despite the absence of B-cells. In addition, T-cells isolated from
      NOD.microMT mice were diabetogenic in 22% of NOD.scid recipients. Together, these
      results indicate that B-cells are not an absolute requirement for the generation
      or effector function of an islet-reactive T-cell repertoire in NOD mice. We
      suggest that conditions favoring rapid lymphocyte expansion can reveal
      autoreactive T-cell activity and precipitate disease in genetically susceptible
      individuals.

PMID- 11289041
TI  - Mucosal antigen primes diabetogenic cytotoxic T-lymphocytes regardless of dose or
      delivery route.
AB  - Administration of antigens via mucosal routes, such as orally or intranasally,
      can induce specific immunological tolerance and has been used as a rational basis
      for the treatment of autoimmune diseases, including type 1 diabetes. Recently,
      however, orally delivered antigens were shown to induce CD8 cytotoxic T
      lymphocytes (CTLs) capable of causing autoimmune diabetes. In this report, we
      have examined several mucosal routes for their ability to induce CTLs and
      autoimmune diabetes, with the aim of identifying approaches that would maximize
      tolerance and minimize CTL generation. In normal C57BL/6 mice, ovalbumin (OVA)
      delivered by either the oral or nasal routes or by aerosol inhalation was able to
      prime CTL immunity in both high- and low-dose regimens. To address the relevance
      of these CTLs to autoimmune disease, OVA was given to mice that transgenically
      expressed this antigen in their pancreatic beta-cells. Irrespective of antigen
      dose or the route of delivery, mucosal OVA triggered diabetes, particularly after
      intranasal administration. These findings suggest that CTL immunity is likely to
      be a consequence of mucosal antigen delivery, regardless of the regimen, and
      should be considered in the clinical application of mucosal tolerance to
      autoimmune disease prevention.

PMID- 11289042
TI  - Glucagon-like peptide 1 increases secretory burst mass of pulsatile insulin
      secretion in patients with type 2 diabetes and impaired glucose tolerance.
AB  - The insulinotropic gut hormone glucagon-like peptide (GLP)-1 increases secretory
      burst mass and the amplitude of pulsatile insulin secretion in healthy volunteers
      without affecting burst frequency. Effects of GLP-1 on secretory mechanisms in
      type 2 diabetic patients and subjects with impaired glucose tolerance (IGT) known
      to have impaired pulsatile release of insulin have not yet been studied. Eight
      type 2 diabetic patients (64+/-9 years, BMI 28.9+/-7.2 kg/m2, HbA1c 7.7+/-1.3%)
      and eight subjects with IGT (63+/-10 years, BMI 31.7+/-6.4 kg/m2, HbA1c 5.7+/
      0.4) were studied on separate occasions in the fasting state during the continued
      administration of exogenous GLP-1 (1.2 pmol x kg(-1) x min(-1), started at 10:00
      P.M. the evening before) or placebo. For comparison, eight healthy volunteers
      (62+/-7 years, BMI 27.7+/-4.8 kg/m2, HbA1c 5.4+/-0.5) were studied only with
      placebo. Blood was sampled continuously over 60 min (roller-pump) in 1-min
      fractions for the measurement of plasma glucose and insulin. Pulsatile insulin
      secretion was characterized by deconvolution, autocorrelation, and spectral
      analysis and by estimating the degree of randomness (approximate entropy). In
      type 2 diabetic patients, exogenous GLP-1 at approximately 90 pmol/l improved
      plasma glucose concentrations (6.4+/-2.1 mmol/l vs. placebo 9.8+/-4.1 mmol/l, P =
      0.0005) and significantly increased mean insulin burst mass (by 68%, P = 0.007)
      and amplitude (by 59%, P = 0.006; deconvolution analysis). In IGT subjects, burst
      mass was increased by 45% (P = 0.019) and amplitude by 38% (P = 0.02). By
      deconvolution analysis, insulin secretory burst frequency was not affected by GLP
      1 in either type 2 diabetic patients (P = 0.15) or IGT subjects (P = 0.76).
      However, by both autocorrelation and spectral analysis, GLP-1 prolonged the
      period (lag time) between subsequent maxima of insulin concentrations
      significantly from approximately 9 to approximately 13 min in both type 2
      diabetic patients and IGT subjects. Under placebo conditions, parameters of
      pulsatile insulin secretion were similar in normal subjects, type 2 diabetic
      patients, and IGT subjects based on all methodological approaches (P > 0.05). In
      conclusion, intravenous GLP-1 reduces plasma glucose in type 2 diabetic patients
      and improves the oscillatory secretion pattern by amplifying insulin secretory
      burst mass, whereas the oscillatory period determined by autocorrelation and
      spectral analysis is significantly prolonged. This was not the case for the
      interpulse interval determined by deconvolution. Together, these results suggest
      a normalization of the pulsatile pattern of insulin secretion by GLP-1, which
      supports the future therapeutic use of GLP-1-derived agents.

PMID- 11289043
TI  - Glucagon-like peptide 1 induces differentiation of islet duodenal homeobox-1
      positive pancreatic ductal cells into insulin-secreting cells.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone capable of restoring
      normal glucose tolerance in aging glucose-intolerant Wistar rats. Whether the
      antidiabetic properties of GLP-1 are exclusively due to its insulin secretory
      activity remains to be determined. A GLP-1-dependent differentiation of
      pancreatic precursor cells into mature beta-cells has recently been proposed. The
      aim of this study was to investigate whether pancreatic ductal epithelial cells
      could be differentiated into insulin-secreting cells by exposing them to GLP-1.
      Rat (ARIP) and human (PANC-1) cell lines, both derived from the pancreatic ductal
      epithelium, were used to test this hypothesis. A major difference distinguishes
      these two cell lines: whereas ARIP cells spontaneously express the beta-cell
      differentiation factor islet duodenal homeobox-1 (IDX-1), PANC-1 cells are
      characteristically IDX-1 negative. GLP-1 induced the differentiation of ARIP
      cells into insulin-synthesizing cells, although it did not affect the phenotype
      of PANC-1 cells, as determined by fluorescence-activated cell sorting (FACS)
      analysis. Differentiation of ARIP cells by exposure to human GLP-1 occurs in a
      time- and dose-dependent manner, and this is associated with an increase in IDX-1
      and insulin mRNA levels. Secretion of insulin was also induced in a parallel
      manner, and it was regulated by the concentration of glucose in the culture
      medium. Interestingly, PANC-1 cells, when stably transfected with human IDX-1,
      gained responsiveness to GLP-1 and were able to differentiate into beta-cells, as
      determined by FACS analysis, insulin gene expression, intracellular insulin
      content, and insulin accumulation in the culture medium. Finally, we demonstrated
      that the receptor for GLP-1 is constitutively expressed by ARIP and PANC-1 cells
      and that the mRNA level for this transcript was increased by cellular
      transfection with human IDX-1. In summary, our study provides evidence that GLP-1
      is a differentiation factor for pancreatic ductal cells and that its effect
      requires the expression of IDX-1.

PMID- 11289044
TI  - The novel imidazoline compound BL11282 potentiates glucose-induced insulin
      secretion in pancreatic beta-cells in the absence of modulation of K(ATP) channel
      activity.
AB  - The insulinotropic activity of the novel imidazoline compound BL11282 was
      investigated. Intravenous administration of BL11282 (0.3 mg x kg(-1) x min(-1))
      to anesthetized rats did not change blood glucose and insulin levels under basal
      conditions, but produced a higher increase in blood insulin levels and a faster
      glucose removal from the blood after glucose infusion. Similarly, in isolated
      Wistar rat pancreatic islets, 0.1-100 micromol/l BL11282 potently stimulated
      glucose-induced insulin secretion but did not modulate basal insulin secretion.
      Unlike previously described imidazolines, BL11282 did not block ATP-dependent K+
      channels. Furthermore, the compound stimulated insulin secretion in islets
      depolarized with high concentrations of KCl or permeabilized with electric shock.
      Insulinotropic activity of BL11282 was dependent on activity of protein kinases A
      and C. In pancreatic islets from spontaneously diabetic GK rats, the imidazoline
      compound restored the impaired insulin response to glucose. In conclusion, the
      imidazoline BL11282 constitutes a new class of insulinotropic compounds that
      exerts an exclusive glucose-dependent insulinotropic activity in pancreatic
      islets by stimulating insulin exocytosis.

PMID- 11289045
TI  - Uncoupling protein 2: a possible link between fatty acid excess and impaired
      glucose-induced insulin secretion?
AB  - The mechanism by which long-term exposure of the beta-cell to elevated
      concentrations of fatty acid alters glucose-induced insulin secretion has been
      examined. Exposure of INS-1 beta-cells to 0.4 mmol/l oleate for 72 h increased
      basal insulin secretion and decreased insulin release in response to high
      glucose, but not in response to agents acting at the level of the K(ATP) channel
      (tolbutamide) or beyond (elevated KCl). This also suppressed the glucose-induced
      increase in the cellular ATP-to-ADP ratio. The depolarization of the plasma
      membrane promoted by glucose was decreased after oleate exposure, whereas the
      response to KCl was unchanged. Cells exposed to free fatty acids displayed a
      lower mitochondrial membrane potential and a decreased glucose-induced
      hyperpolarization. The possible implication of uncoupling protein (UCP)-2 in the
      altered secretory response was examined by measuring UCP2 gene expression after
      chronic exposure of the cells to fatty acids. UCP2 mRNA and protein were
      increased twofold by oleate. Palmitate and the nonoxidizable fatty acid
      bromopalmitate had similar effects on UCP2 mRNA, suggesting that UCP2 gene
      induction by fatty acids does not require their metabolism. The data are
      compatible with a role of UCP2 and partial mitochondrial uncoupling in the
      decreased secretory response to glucose observed after chronic exposure of the
      beta-cell to elevated fatty acids, and suggest that the expression and/or
      activity of the protein may modulate insulin secretion in response to glucose.

PMID- 11289046
TI  - Effects of free fatty acids on gluconeogenesis and autoregulation of glucose
      production in type 2 diabetes.
AB  - Effects of endogenously derived free fatty acids (FFAs) on rates of
      gluconeogenesis (GNG) (determined with 2H2O), glycogenolysis (GL), and endogenous
      glucose production (EGP) were studied in 18 type 2 diabetic patients and in 7
      nondiabetic control subjects under three experimental conditions: 1) during an 8
      h fast (from 16-24 h after the last meal), when plasma FFA levels increased
      slowly; 2) during 4 h (from 16-20 h) of nicotinic acid (NA) administration
      (fasting plus NA), when plasma FFAs decreased acutely; and 3) during 4 h (from 20
      24 h) after discontinuation of NA (FFA rebound), when plasma FFAs increased
      acutely. During fasting, FFAs increased from 636 to 711 micromol/l in type 2
      diabetic patients and from 462 to 573 micromol/l in control subjects (P < 0.04),
      but GNG did not change in diabetic patients (6.9 vs. 6.5 micromol x kg(-1) x min(
      1), P > 0.05) or in control subjects (5.1 vs. 5.4 micromol x kg(-1) x min(-1), P
      > 0.05). During fasting plus NA, FFAs decreased in diabetic patients and control
      subjects (from 593 to 193 and from 460 to 162 micromol/l, respectively); GNG
      decreased (from 6.1 to 4.2 and from 4.7 to 3.5 micromol x kg(-1) x min(-1)),
      whereas GL decreased in diabetic patients (from 5.3 to 4.4 micromol x kg(-1) x
      min(-1)) but increased in control subjects (from 5.4 to 7.2 micromol x kg(-1)
      min(-1)). During the FFA rebound, FFAs increased in diabetic patients and control
      subjects (from 193 to 1,239 and from 162 to 1,491 micromol/l, respectively); GNG
      increased (from 4.2 to 5.4 and from 3.4 to 5.3 micromol x kg(-1) x min(-1)
      respectively), and GL decreased (from 4.4 to 3.4 and from 7.3 to 4.3 micromol x
      kg(-1) x min(-1), respectively). In summary, during an extended overnight fast,
      increasing plasma FFA levels stimulated GNG, whereas decreasing FFA levels
      inhibited GNG in both diabetic and control subjects; 20 h after the last meal,
      approximately one-third of GNG in both diabetic and control subjects was
      dependent on FFAs; and autoregulation of EGP by GL in response to decreasing GNG
      was impaired in diabetic patients.

PMID- 11289047
TI  - Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle
      fiber type in type 2 diabetes and obesity.
AB  - In obesity and type 2 diabetes, skeletal muscle has been observed to have a
      reduced oxidative enzyme activity, increased glycolytic activity, and increased
      lipid content. These metabolic characteristics are related to insulin resistance
      of skeletal muscle and are factors potentially related to muscle fiber type. The
      current study was undertaken to examine the interactions of muscle fiber type in
      relation to oxidative enzyme activity, glycolytic enzyme activity, and muscle
      lipid content in obese and type 2 diabetic subjects compared with lean healthy
      volunteers. The method of single-fiber analysis was used on vastus lateralis
      muscle obtained by percutaneous biopsy from 22 lean, 20 obese, and 20 type 2
      diabetic subjects (ages 35+/-1, 42+/-2, and 52+/-2 years, respectively), with
      values for BMI that were similar in obese and diabetic subjects (23.7+/-0.7,
      33.2+/-0.8, and 31.8+/-0.8 kg/m2, respectively). Oxidative enzyme activity
      followed the order of type I > type IIa > type IIb, but within each fiber type,
      skeletal muscle from obese and type 2 diabetic subjects had lower oxidative
      enzyme activity than muscle from lean subjects (P < 0.01). Muscle lipid content
      followed a similar pattern in relation to fiber type, and within each fiber type,
      muscle from obese and type 2 diabetic subjects had greater lipid content (P <
      0.01). In summary, based on single-fiber analysis, skeletal muscle in obese and
      type 2 diabetic subjects mani-fests disturbances of oxidative enzyme activity and
      increased lipid content that are independent of the effect of fiber type.

PMID- 11289048
TI  - A novel small molecule that directly sensitizes the insulin receptor in vitro and
      in vivo.
AB  - Insulin resistance, an important feature of type 2 diabetes, is manifested as
      attenuated insulin receptor (IR) signaling in response to insulin binding. A drug
      that promotes the initiation of IR signaling by enhancing IR autophosphorylation
      should, therefore, be useful for treating type 2 diabetes. This report describes
      the effect of a small molecule IR sensitizer, TLK16998, on IR signaling. This
      compound activated the tyrosine kinase domain of the IR beta-subunit at
      concentrations of 1 micromol/l or less but had no effect on insulin binding to
      the IR alpha-subunit even at much higher concentrations. TLK16998 alone had no
      effect on IR signaling in mouse 3T3-L1 adipocytes but, at concentrations as low
      as 3.2 micromol/l, enhanced the effects of insulin on the phosphorylation of the
      IR beta-subunit and IR substrate 1, and on the amount of phosphatidylinositol 3
      kinase that coimmunoprecipitated with IRS-1. Phosphopeptide mapping revealed that
      the effect of TLK16998 on the IR was associated with increased tyrosine
      phosphorylation of the activation loop of the beta-subunit tyrosine kinase
      domain. TLK16998 also increased the potency of insulin in stimulating 2-deoxy-D
      glucose uptake in 3T3-L1 adipocytes, with a detectable effect at 8 micromol/l and
      a 10-fold increase at 40 micromol/l. In contrast, only small effects were
      observed on IGF-1-stimulated 2-deoxy-D-glucose uptake. In diabetic mice,
      TLK16998, at a dose of 10 mg/kg, lowered blood glucose levels for up to 6 h.
      These results suggest, therefore, that small nonpeptide molecules that directly
      sensitize the IR may be useful for treating type 2 diabetes.

PMID- 11289049
TI  - The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the
      insulin receptor and inhibits insulin signaling more effectively than the common
      K allele variant (LYS121).
AB  - When overexpressed, the membrane glycoprotein PC-1 may play a role in human
      insulin resistance through the inhibition of insulin receptor (IR)
      autophosphorylation. A PC-1 variant (K121Q, with lysine 121 replaced by
      glutamine) is also associated with whole-body insulin resistance when not
      overexpressed. To better understand the effects of the Q allele on IR function
      and downstream signaling, we transfected cultured cells with cDNAs for either the
      Q or the K alleles. In human MCF-7 cells, the Q allele was severalfold more
      effective (P < 0.05-0.01) than the K allele in reducing insulin stimulation of IR
      autophosphorylation, insulin receptor substrate-1 phosphorylation,
      phosphatidylinositol 3-kinase activity, glycogen synthesis, and cell
      proliferation. Similar data on IR autophosphorylation inhibition were also
      obtained in mouse R-/hIR and human HEK 293 cell lines. In transfected MCF-7
      cells, 125I-labeled insulin binding and IR content were unchanged, and PC-1
      overexpression did not influence IGF-1 stimulation of IGF-1 receptor
      autophosphorylation. Both the Q and K alleles directly interacted with the IR, as
      documented by coimmunoprecipitation assays. This interaction was greater for the
      Q allele than for the K allele (P < 0.01), suggesting that direct PC-1-IR
      interactions are important for the PC-1 inhibitory effect on insulin signaling.
      In conclusion, the Q allele has stronger inhibitory activity on IR function and
      insulin action than the more common K allele, and this is likely a consequence of
      the intrinsic characteristics of the molecule, which more strongly interacts with
      the IR.

PMID- 11289050
TI  - Increased QTc dispersion is related to blunted circadian blood pressure variation
      in normoalbuminuric type 1 diabetic patients.
AB  - A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both
      predict an increased risk of cardiovascular events in diabetic as well as
      nondiabetic subjects. The relationship between these two parameters remains
      unclear. The role of diabetic autonomic neuropathy in both QT dispersion and
      circadian BP variation has been proposed, but data have been conflicting. The aim
      of the present study was to describe associations between QT dispersion and
      circadian BP variation as well as autonomic function in type 1 diabetic patients.
      In 106 normoalbuminuric (urinary albumin excretion <20 microg/min) normotensive
      patients, we performed 24-h ambulatory BP (Spacelabs 90207) and short-term (three
      times in 5 min) power spectral analysis of RR interval oscillations, as well as
      cardiovascular reflex tests (deep breathing test, postural heart rate, and BP
      response). No patient had received (or had earlier received) antihypertensive or
      other medical treatment apart from insulin. In a resting 12-lead
      electrocardiogram, the QT interval was measured by the tangent method in all
      leads with well-defined T-waves. The measurement was made by one observer blinded
      to other data. The QT interval was corrected for heart rate using Bazett's
      formula. The QTc dispersion was defined as the difference between the maximum and
      the minimum QTc interval in any of the 12 leads. When comparing patients with QTc
      dispersion below and above the median (43 ms), the latter had significantly
      higher night BP (114/67 vs. 109/62 mmHg, P < 0.003/P < 0.001), whereas day BP was
      comparable (129/81 vs. 127/79 mmHg). Diurnal BP variation was blunted in the
      group with QTc dispersion >43 ms with significantly higher night/day ratio, both
      for systolic (88.8 vs. 86.2%, P < 0.01) and diastolic (83.1 vs. 79.5%, P < 0.01)
      BP. The association between QTc dispersion and diastolic night BP persisted after
      controlling for potential confounders such as sex, age, duration of diabetes,
      urinary albumin excretion, and HbA1c. Power spectral analysis suggested an
      altered sympathovagal balance in patients with QTc dispersion above the median
      (ratio of low-frequency/high-frequency power: 1.0 vs. 0.85, P < 0.01). In
      normoalbuminuric type 1 diabetic patients, increased QTc dispersion is associated
      with reduced nocturnal fall in BP and an altered sympathovagal balance. This
      coexistence may be operative in the ability of these parameters to predict
      cardiovascular events.

PMID- 11289051
TI  - Effect of 3 years of antihypertensive therapy on renal structure in type 1
      diabetic patients with albuminuria: the European Study for the Prevention of
      Renal Disease in Type 1 Diabetes (ESPRIT).
AB  - In the treatment of diabetic nephropathy, ACE inhibitor therapy reduces albumin
      excretion and slows the rate of decline in glomerular filtration rate (GFR). Our
      study was designed to investigate whether these effects lay in amelioration of
      the underlying glomerular structural abnormalities. A total of 54 type 1 diabetic
      patients with albuminuria and blood pressure (BP) <150/90 mmHg were randomized to
      receive 10 mg enalapril once daily, 10 mg nifedipine retard twice daily, or
      placebo in a multicenter double-blind study of 3 years' duration. Renal biopsy
      was performed at baseline and follow-up, and tissue was analyzed by standard
      morphometric methods. BP, GFR, albumin excretion rate (AER), and HbA1c were
      measured every 6 months. Enalapril lowered AER after 6 months by 26% (P < 0.05);
      however, this reduction was not sustained at 3 years. There was no significant
      effect of nifedipine or placebo on AER. GFR decreased by a similar average rate
      of 4.1 ml x min(-1) x year(-1) (95% CI 2.6-5.6) in all three groups. BP and HbA1c
      were unchanged throughout the study in all groups. At baseline, nearly all
      biopsies showed classic appearances of diabetic glomerulopathy. There was no
      detectable effect of enalapril compared with either nifedipine or placebo on
      renal structure over 3 years. However, we found that patients with increased AER
      have established glomerulopathy and a progressive average decline in GFR of 4.1
      ml x min(-1) x year(-1) in the absence of overt hypertension, and baseline AER
      appeared predictive of subsequent mesangial volume fraction (r = 0.20, P =
      0.0018). In this small cohort of nonhypertensive patients studied for 3 years,
      disease evolution appears unaffected by treatment with either enalapril or
      nifedipine.

PMID- 11289052
TI  - Diabetes accelerates smooth muscle accumulation in lesions of atherosclerosis:
      lack of direct growth-promoting effects of high glucose levels.
AB  - In combination with other factors, hyperglycemia may cause the accelerated
      progression of atherosclerosis in people with diabetes. Arterial smooth muscle
      cell (SMC) proliferation and accumulation contribute to formation of advanced
      atherosclerotic lesions. Therefore, we investigated the effects of hyperglycemia
      on SMC proliferation and accumulation in vivo and in isolated arteries and SMCs
      by taking advantage of a new porcine model of diabetes-accelerated
      atherosclerosis, in which diabetic animals are hyperglycemic without receiving
      exogenous insulin. We show that diabetic animals fed a cholesterol-rich diet,
      like humans, develop severe lesions of atherosclerosis characterized by SMC
      accumulation and proliferation, whereas lesions in nondiabetic animals contain
      fewer SMCs after 20 weeks. However, high glucose (25 mmol/l) does not directly
      stimulate the proliferation of SMCs in isolated arterial tissue from diabetic or
      nondiabetic animals, or of cultured SMCs from these animals or from humans.
      Furthermore, the mitogenic actions of platelet-derived growth factor, IGF-I, or
      serum are not enhanced by high glucose. High glucose increases SMC glucose
      metabolism through the citric acid cycle and the pentose phosphate pathway by 240
      and 90%, respectively, but <10% of consumed glucose is metabolized through these
      pathways. Instead, most of the consumed glucose is converted into lactate and
      secreted by the SMCs. Thus, diabetes markedly accelerates SMC proliferation and
      accumulation in atherosclerotic lesions. The stimulatory effect of diabetes on
      SMCs is likely to be mediated by effects secondary to the hyperglycemic state.

PMID- 11289053
TI  - Familial aggregation of coronary artery calcium in families with type 2 diabetes.
AB  - Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic
      cardiovascular disease, including subclinical atherosclerosis as measured by
      noninvasive procedures. However, the role of genetic factors that contribute to
      various measures of subclinical atherosclerosis is largely unknown. We
      hypothesize that subclinical atherosclerosis, measured as coronary artery
      calcification (CAC), will be extensive in individuals with type 2 diabetes and
      that its presence depends on both genetic and environmental factors. The genetic
      factors should result in the familial aggregation of CAC. To determine the extent
      of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122
      individuals with type 2 diabetes (mean age 60 years) and 13 individuals without
      diabetes in 56 families. CAC was measured by fast-gated helical computed
      tomography. Other measured factors included blood pressure, body size, lipids,
      HbA1c, and self-reported medical history. To test for an association between CAC
      and these factors while accounting for the potential familial correlation of CAC,
      generalized estimating equations were used. CAC was detectable in 80% of
      individuals with diabetes (median score 84, range 0-5,776). Extent of CAC,
      adjusted for age, was positively associated with male sex (P = 0.0003), reduced
      HDL (P = 0.02), albumin-to-creatinine ratio (P = 0.008), and cigarette pack-years
      (P = 0.03). CAC was also positively associated with a history of angina,
      myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA1c and
      fasting glucose were positively, but nonsignificantly, associated with the extent
      of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and
      diabetes status, was heritable (h2 = 0.50; P = 0.009). In multivariate analysis
      with additional adjustment for HDL, BMI, hypertension, and smoking, h2 = 0.40 (P
      = 0.038). These results suggest that strong (independent) genetic factors as well
      as environmental factors contribute to the variance of CAC in individuals with
      type 2 diabetes. In these data, CAC seems heritable and may serve as an important
      feature in designing studies to map genes contributing to both atherosclerosis
      and type 2 diabetes.

PMID- 11289054
TI  - Angiotensin II induces expression of the Tie2 receptor ligand, angiopoietin-2, in
      bovine retinal endothelial cells.
AB  - Recent studies have shown that angiopoietins (Angs) and their receptor, Tie2,
      play a role in vascular integrity and neovascularization. The renin-angiotensin
      system has been hypothesized to contribute to the development of diabetic
      retinopathy. In this study, we investigated the effect of angiotensin II (AII) on
      Ang1 and Ang2 expression in cultured bovine retinal endothelial cells (BRECs).
      AII stimulated Ang2 but not Ang1 mRNA expression in a dose- and time-dependent
      manner. This response was inhibited completely by angiotensin type 1 receptor
      (AT1) antagonist. AII increased the transcription of Ang2 mRNA, but did not
      change the half-life. Protein kinase C (PKC) inhibitor completely inhibited AII
      induced Ang2 expression, and the mitogen-activated protein kinase (MAPK)
      inhibitor also inhibited it by 69.4+/-15.6%. In addition, we confirmed the
      upregulation of Ang2 in an AII-induced in vivo rat corneal neovascularization
      model. These data suggest that AII stimulates Ang2 expression through AT1
      receptor-mediated PKC and MAPK pathways in BREC, and AII may play a novel role in
      retinal neovascularization.

PMID- 11289056
TI  - The Gly972Arg polymorphism in the insulin receptor substrate-1 gene contributes
      to the variation in insulin secretion in normal glucose-tolerant humans.
AB  - The Gly972Arg polymorphism in the insulin receptor substrate (IRS)-1 was found in
      some studies to have a higher prevalence in type 2 diabetic subjects than in
      control subjects. Previously, transfection of IRS-1 with this polymorphism into
      insulin-secreting cells resulted in a marked reduction of glucose-stimulated
      insulin secretion compared with the wild-type transfected cells. In the present
      study, we compared insulin secretion in well-matched normal glucose-tolerant
      subjects with and without this polymorphism. Several validated indexes of beta
      cell function from the oral glucose tolerance test were significantly lower in
      X/Arg (n = 31) compared with Gly/Gly (n = 181) (P between 0.002 and 0.05),
      whereas insulin sensitivity (measured with a euglycemic clamp) was not different.
      During a modified hyperglycemic clamp, insulin secretion rates were significantly
      lower in Gly/Arg (n = 8) compared with Gly/Gly (n = 36) during the first phase
      (1,711+/-142 vs. 3,014+/-328 pmol/min, P = 0.05) and after maximal stimulation
      with arginine (5,340+/-639 vs. 9,075+/-722 pmol/min, P = 0.03). In summary, our
      results suggest that the Gly972Arg polymorphism in IRS-1 is associated with
      decreased insulin secretion in response to glucose but not with insulin
      sensitivity. It is possible that this polymorphism causes insulin resistance at
      the level of the beta-cell and contributes to the polygenic etiology of type 2
      diabetes.

PMID- 11289055
TI  - Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma2
      gene is associated with increased antilipolytic insulin sensitivity.
AB  - The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor
      (PPAR)-gamma2 is associated with reduced transcriptional activity in vitro and
      increased insulin sensitivity in humans in vivo. The mechanism by which this
      polymorphism influences insulin sensitivity in humans is unclear. PPAR-gamma2 is
      mainly expressed in adipocytes, and free fatty acids released from adipose tissue
      are key mediators of peripheral insulin resistance. Therefore, we examined
      insulin suppression of lipolysis in 51 subjects without (Pro/Pro) and 17 subjects
      with the polymorphism (X/Ala). Both groups were lean (BMI <27.0 kg/m2) and
      matched for age, BMI, waist-to-hip ratio, and sex. The isotopically (infusion of
      d5 glycerol) determined glycerol rate of appearance was used as an index of
      lipolysis. Insulin sensitivity of lipolysis was expressed as the insulin
      concentration resulting in half-maximal suppression (EC50). This was directly
      determined during a three-step hyperinsulinemic-euglycemic clamp (n = 21) or
      estimated indirectly during a standard hyperinsulinemic-euglycemic clamp (n =
      47). The insulin sensitivity index (ISI) of glucose disposal was 0.095+/-0.006
      micromol x kg(-1) x min(-1) x pmol(-1) x l(-1) in the control group and 0.129+/
      0.008 micromol x kg(-1) x min(-1) x pmol(-1) x l(-1) in the X/Ala group (P =
      0.003). The EC50 was 56+/-2 pmol/l in the control group and 44+/-3 pmol/l in the
      X/Ala group (P = 0.001). The EC50 of lipolysis and ISI was significantly
      correlated (r = 0.42, P = 0.002). In conclusion, in lean subjects, the Pro12Ala
      polymorphism is associated with increased insulin sensitivity of glucose disposal
      and suppression of lipolysis. This result suggests that an altered
      transcriptional activity of PPAR-gamma2 in X/Ala subjects either causes a more
      efficient suppression of lipolysis in adipose tissue, which in turn results in
      improved insulin-stimulated glucose disposal in muscle, or, alternatively,
      beneficially affects insulin signaling in both tissues independently of one
      another.

PMID- 11289057
TI  - The peroxisome proliferator-activated receptor-gamma2 Pro12A1a variant:
      association with type 2 diabetes and trait differences.
AB  - Recent studies have identified a common proline-to-alanine substitution
      (Pro12Ala) in the peroxisome proliferator-activated receptor-gamma2 (PPAR
      gamma2), a nuclear receptor that regulates adipocyte differentiation and possibly
      insulin sensitivity. The Pro12Ala variant has been associated in some studies
      with diabetes-related traits and/or protection against type 2 diabetes. We
      examined this variant in 935 Finnish subjects, including 522 subjects with type 2
      diabetes, 193 nondiabetic spouses, and 220 elderly nondiabetic control subjects.
      The frequency of the Pro12Ala variant was significantly lower in diabetic
      subjects than in nondiabetic subjects (0.15 vs. 0.21; P = 0.001). We also
      compared diabetes-related traits between subjects with and without the Pro12Ala
      variant within subgroups. Among diabetic subjects, the variant was associated
      with greater weight gain after age 20 years (P = 0.023) and lower triglyceride
      levels (P = 0.033). Diastolic blood pressure was higher in grossly obese (BMI >40
      kg/m2) diabetic subjects with the variant. In nondiabetic spouses, the variant
      was associated with higher fasting insulin (P = 0.033), systolic blood pressure
      (P = 0.021), and diastolic blood pressure (P = 0.045). These findings support a
      role for the PPAR-gamma2 Pro12Ala variant in the etiology of type 2 diabetes and
      the insulin resistance syndrome.

PMID- 11289058
TI  - The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to
      development of diabetes in the general population: possible involvement in
      impairment of insulin secretion in individuals with type 2 diabetes.
AB  - The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator
      activated receptor-gamma differ among ethnic groups, and its relationship with
      diabetes and associated diseases is controversial. The prevalence of this
      polymorphism and its effects on clinical characteristics have now been evaluated
      with a large number of Japanese individuals with type 2 diabetes (n = 2,201) and
      normal control subjects (n = 1,212) recruited by 10 institutions located in seven
      different cities in Japan. The allele frequency for the Ala12 variant was
      significantly lower in the type 2 diabetic group than in the control group (2.39
      vs. 4.13%, P = 0.000054). However, compared with subjects without the Ala12
      variant, the diabetic subjects with this variant exhibited a significantly higher
      serum concentration of total cholesterol (P = 0.001), manifested a reduced
      capacity for insulin secretion as evaluated by homeostasis model assessment (P =
      0.007), and tended to possess a higher level of HbA1c. These data suggest that
      the Ala12 variant is associated with a reduced risk for the development of
      diabetes in the general population, but that it may be also a risk factor for
      insulin deficiency and disease severity in individuals with type 2 diabetes.

PMID- 11289059
TI  - Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a
      permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes
      autoantigen.
AB  - Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells
      in genetically susceptible individuals. Growing evidence suggests that
      genetically determined variation in the expression of self-antigens in thymus may
      affect the shaping of the T-cell repertoire and susceptibility to autoimmunity.
      For example, both allelic variation and parent-of-origin effects influence the
      thymic expression of insulin (a known type 1 diabetes autoantigen), and insulin
      gene transcription levels in thymus inversely correlate with susceptibility in
      both humans and transgenic models. It is unclear why patients lose tolerance to
      IA-2 (insulinoma-associated tyrosine phosphatase-like protein, or islet cell
      antigen 512 [ICA512]), especially because IA-2 polymorphisms are not associated
      with type 1 diabetes. We report that alternative splicing determines differential
      IA-2 expression in islets compared with thymus and spleen. Islets express full
      length mRNA and two alternatively spliced transcripts, whereas thymus and spleen
      exclusively express an alternatively spliced transcript lacking exon 13. This
      encodes for the transmembrane (TM) and juxta-membrane (JM) domains that comprise
      several type 1 diabetes target epitopes, supporting the concept that tolerance to
      IA-2 epitopes not expressed in lymphoid organs may not be achieved. We propose
      differential splicing as a regulatory mechanism of gene expression playing a
      permissive role in the development of autoimmune responses to IA-2. Our findings
      also show that candidate gene expression studies can help in dissecting the
      complex genetic determinants of a multifactorial disease such as type 1 diabetes.

PMID- 11289061
TI  - Measurements of renal glucose release.

PMID- 11289060
TI  - A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with
      reduced energy expenditure.
AB  - Brain dopaminergic pathways play a major role in the control of movement. Absence
      of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and
      hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional
      impairment of the receptor and is associated with higher BMI in some populations.
      We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy
      expenditure. Here we report that total energy expenditure (doubly labeled water)
      measured in 89 nondiabetic Pima Indians was 244 kcal/ day lower in homozygotes
      for the Cys311-encoding allele when compared with those heterozygous and
      homozygous for the Ser311-encoding allele (P = 0.056). The 24-h resting energy
      expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87
      kcal/day lower in homozygotes for the Cys311-encoding allele when compared with
      those heterozygous and homozygous for the Ser311-encoding allele (P = 0.026).
      These findings are the first evidence that a genetic mutation is associated with
      reduced energy expenditure in humans. Because the impact of this mutation on
      human obesity is small, we suggest that either the energy deficit induced is not
      large enough to significantly influence body weight in this population and/or
      that the Cys311-encoding allele is also associated with reduced energy intake.

PMID- 11289063
TI  - Kinetics of the intracellular differentiation of Leishmania amazonensis and
      internalization of host MHC molecules by the intermediate parasite stages.
AB  - The establishment of Leishmania in mammals depends on the transformation of
      metacyclic promastigotes into amastigotes within macrophages. The kinetics of
      this process was examined using mouse macrophages infected with metacyclic
      promastigotes of L. amazonensis. The appearance of amastigote characteristics,
      including large lysosome-like organelles called megasomes, stage-specific
      antigens, high cysteine protease activity and sensitivity to L-leucine methyl
      ester, was followed over a 5-day period. Megasomes were observed at 48 h but
      probable precursors of these organelles were detected at 12h p.i. The
      promastigote-specific molecules examined were down-regulated within 5 to 12h
      after phagocytosis whereas the amastigote-specific antigens studied were
      detectable from 2 to 12-24 h. An increase in the cysteine protease activity and
      in sensitivity to L-leucine methyl ester of the parasites was detected from 24 h.
      The data indicate that at 48 h p.i., parasites exhibit several amastigote
      features but that complete differentiation requires at least 5 days. The
      appearance of megasomes or of megasome precursors and the rise in cysteine
      protease activity correlate quite well with the capacity of parasites to
      internalize and very likely degrade host MHC molecules. The fact that
      internalization by the parasites of host cell molecules occurs very early during
      the differentiation process argues for a role of this mechanism in parasite
      survival.

PMID- 11289062
TI  - Detection of Leishmania infantum by PCR, serology and cellular immune response in
      a cohort study of Brazilian dogs.
AB  - The sensitivity and specificity of PCR, serology (ELISA) and lymphoproliferative
      response to Leishmania antigen for the detection of Leishmania infantum infection
      were evaluated in a cohort of 126 dogs exposed to natural infection in Brazil.
      For PCR, Leishmania DNA from bone-marrow was amplified with both minicircle and
      ribosomal primers. The infection status and time of infection of each dog were
      estimated from longitudinal data. The sensitivity of PCR in parasite-positive
      samples was 98%. However, the overall sensitivity of PCR in post-infection
      samples, from dogs with confirmed infection, was only 68%. The sensitivity of PCR
      varied during the course of infection, being highest (78-88%) 0-135 days post
      infection and declining to around 50% after 300 days. The sensitivity of PCR also
      varied between dogs, and was highest in sick dogs. The sensitivity of serology
      was similar in parasite-positive (84%), PCR-positive (86%) and post-infection
      (88%) samples. The sensitivity of serology varied during the course of infection,
      being lowest at the time of infection and high (93-100%) thereafter. Problems in
      determining the specificity of serology are discussed. The sensitivity and
      specificity of cellular responsiveness were low. These data suggest that PCR is
      most useful in detecting active or symptomatic infection, and that serology can
      be a more sensitive technique for the detection of all infected dogs.

PMID- 11289065
TI  - The spliced leader RNA gene array in phloem-restricted plant trypanosomatids
      (Phytomonas) partitions into two major groupings: epidemiological implications.
AB  - The arbitrary genus Phytomonas includes a biologically diverse group of
      kinetoplastids that live in a wide variety of plant environments. To understand
      better the subdivisions within the phytomonads and the variability within groups,
      the exon, intron and non-transcribed spacer sequences of the spliced leader RNA
      gene were compared among isolates of the phloem-restricted members. A total of 29
      isolates associated with disease in coconut, oil palm and red ginger (Alpinia
      purpurata, Zingibreaceae) were examined, all originating from plantations in
      South America and the Caribbean over a 12-year period. Analysis of non
      transcribed spacer sequences revealed 2 main groups, I and II; group II could be
      further subdivided into 2 subgroups, IIa and Ilb. Three classes of spliced leader
      (SL) RNA gene were seen, with SLI corresponding to group I, SLIIa to group lIa,
      and SLIIb to group IIb. Two isolates showed some characteristics of both major
      groups. Group-specific oligonucleotide probes for hybridization studies were
      tested, and a multiplex amplification scheme was devised to allow direct
      differentiation between the 2 major groups of phloem-restricted Phytomonas. These
      results provide tools for diagnostic and molecular epidemiology of plant
      trypanosomes that are pathogenic for commercially important flowers and palms.

PMID- 11289064
TI  - Comparative analysis of the 14-3-3 gene and its expression in Echinococcus
      granulosus and Echinococcus multilocularis metacestodes.
AB  - It was suggested that the unlimited proliferative capacity of the Echinococcus
      multilocularis metacestode may be related to overproduction of the 14-3-3
      protein. As is known, the proliferative capacities of E. granulosus and E.
      multilocularis metacestodes are very different. By comparing the expression
      levels of the 14-3-3 gene between in vitro-obtained E. granulosus and E.
      multilocularis metacestodes, we were able to provide experimental evidence of the
      potential relation between 14-3-3 over-expression and tumour-like growth in E.
      multilocularis metacestodes. RT-PCR and Northern blot experiments indicated that
      14-3-3 expression level is about 4-fold higher in the E. multilocularis
      metacestode. This differential expression was confirmed both by immunoblotting
      and immunocytochemistry experiments, which allowed detection of the protein in
      the cyst wall from E. multilocularis but not in the cyst wall from E. granulosus.
      The alignment of the Echinococcus 14-3-3 cDNA sequence with known 14-3-3 isoforms
      from other organisms, grouped the parasite sequence into the tumour growth
      related isoforms. The known relation between over-expression of some 14-3-3
      isoforms and tumour-related processes, together with the present results, suggest
      that the Echinococcus 14-3-3 protein could be one of the molecules responsible
      for the differences between E. granulosus and E. multilocularis metacestode
      growth behaviour.

PMID- 11289066
TI  - Cytokine mRNA expression in pigs infected with Schistosoma japonicum.
AB  - The pig is a natural host of Schistosoma japonicum and a useful animal model of
      human disease. In the present study mRNA levels of Th1 (IFN-gamma) and Th2 (IL-10
      and IL-4) cytokines were assessed by RT-PCR within tissues from infected pigs.
      Twelve Danish crossbred pigs were infected by intramuscular injection or orally
      with 1000 cercariae. Six other pigs served as non-infected controls. Liver and
      intestinal tissues were collected 10 weeks post-infection, and analysed for their
      relative levels of cytokine mRNA. Infected pigs developed a Th2 response as
      characterized by the increased level of mRNA encoding for IL-4 and IL-10 in their
      large intestine (caecum and colon). In contrast, levels of IFN-gamma did not
      differ between control and infected animals although variation between animals
      was observed. When comparing the immune response of orally and intramuscularly
      infected animals, we found that orally infected pigs produced higher IL-4 and IL
      10 levels in their caecum and colon respectively. This stronger Th2 response
      correlated with a previously reported delay in maturation of infection following
      oral infection. The cytokine expression levels in tissue samples taken from
      lesion sites and in nearby areas, without obvious lesions, were then compared.
      Subsequent to an oral infection, the Th2 type cytokine production was higher in
      the lesion sites of the liver. In conclusion, this study is the first
      demonstration of IL-4 and IL-10 cytokine response in pig tissues during S.
      japonicum infection.

PMID- 11289067
TI  - Inhibition of nitric oxide synthase activity reduces liver injury in murine
      schistosomiasis.
AB  - We investigated the involvement of nitric oxide in Schistosoma-induced liver
      injury. We found that inducible nitric oxide synthase mRNA became detectable in
      the liver at the onset of parasite egg laying and levels then increased as the
      eggs accumulated in the organ. Enzyme concentration and activity paralleled mRNA
      levels. The event was a direct effect of egg deposition, as it occurred in the
      liver after natural infection, or in the lungs after i.v. injection of the eggs.
      However, nitric oxide seems to have no direct effect on the eggs since in vitro
      assays showed that the nitric oxide donor SIN-1 did not alter the ability of the
      eggs to hatch. L-Arginine and L-NAME, a nitric oxide synthase inhibitor, were
      administered to infected mice in an attempt to increase or reduce nitric oxide
      production, respectively. Arginine had no effect on the disease, whereas the
      inhibitor led to a marked decrease of hepatic injury with, in particular, reduced
      fibrosis and decreased lipid peroxidation. In conclusion, not only is inducible
      nitric oxide synthase activity unlikely to exert an anti-microbicidal effect
      against the egg stage of S. mansoni but it might lead to deleterious effects in
      the liver and therefore contribute to the pathology.

PMID- 11289068
TI  - Identification, isolation and characterization of a Fyn-like tyrosine kinase from
      Schistosoma mansoni.
AB  - Growth and development of adult schistosomes requires permanent communication
      processes of the parasites with their specific host environment and,
      additionally, between the two genders. Accumulating evidence suggests that, at
      the molecular level, the mandatory interactions are mediated by signal
      transduction processes. During recent years, a considerable interest has emerged
      in the identification of signalling molecules from this parasite and to elucidate
      their roles during development. In this organism, a number of different molecules
      have been identified which belong to diverse classes of evolutionary conserved
      signal transduction cascades. However, up to now no representative of the
      conserved family of cellular tyrosine kinases has been identified. In this study
      we present a suitable approach to identify this class of molecules and
      demonstrate the successful cloning and molecular characterization of one of the
      isolated genes, the tyrosine kinase 5 (TK5). An unexpected finding was that in
      the Liberian strain of Schistosoma mansoni the TK5 gene exhibits an allelic
      polymorphism.

PMID- 11289069
TI  - The schistosome egg: development and secretions.
AB  - We have investigated the development of the schistosome egg and its secretions in
      order to understand how it migrates through gut tissues and also initiates
      pathology in the liver. We show by electron microscopy that the subshell envelope
      is absent in the newly deposited egg, but appears very early and differentiates
      as development progresses. In the mature egg, this nucleated envelope contains
      extensive endoplasmic reticulum, suggestive of a protein synthetic capacity.
      Furthermore, Reynolds' layer only appears between the envelope and the egg-shell
      in the mature egg and may represent its accumulated secretions. We have
      biosynthetically labelled and collected the secretions (ESP) released by mature
      but not immature eggs during culture. Their fractionation by SDS-PAGE reveals a
      simple pattern of 6 bands, differing markedly in composition from soluble egg
      antigen preparations. Electrophoresis in casein substrate gels demonstrates the
      presence of 2 distinct proteases in the egg secretions. By immunocytochemistry,
      ESP localized predominantly to the envelope of the mature egg, suggesting that
      this layer rather than the miracidium is the source of egg secretions.

PMID- 11289070
TI  - Ammonia-induced cellular and immunological changes in juvenile Cyprinus carpio
      infected with the blood fluke Sanguinicola inermis.
AB  - Immunological and structural changes in the thymus and pronephros of Cyprinus
      carpio infected with the blood fluke, Sanguinicola inermis for 30 days, and
      exposed to 0.5 mg NH4+/1 for 48 and 168 h were investigated. Ultrastructural
      observations revealed cell disruption and highly vacuolated cytoplasm in the
      thymus. Of the cells that remained intact there was a significant increase in
      thrombocytes after 48 h exposure to the pollutant. In addition, there was a
      decrease in lymphocytes following exposure to ammonia at both time-periods
      studied. In contrast the pronephros of fish exposed to the pollutant underwent
      relatively mild changes in cellular architecture although ammonia and time of
      exposure had significant effects on the proportions of several leucocyte types. A
      significant decrease in neutrophils, thrombocytes and lymphocytes occurred in
      fish exposed to the pollutant for 168 h. Pronephric lymphocyte stimulation (cpm)
      by Con A and PWM increased in vitro, whereas the stimulation index was reduced in
      infected fish exposed to ammonia. Changes in the immune organs of S. inermis
      infected carp treated with pollutant were both organ- and time-specific. The
      possible reasons for this are discussed and significance in relationship to
      parasitization assessed.

PMID- 11289071
TI  - Electrophysiological analysis of responses of adult females of Brugia pahangi to
      some chemicals.
AB  - Electrophysiological techniques were used to obtain recordings of extracellular
      electrical activity from the anterior end of live adult females of Brugia
      pahangi. Stimulation with 100 mM, 10 mM and 1 mM acetylcholine resulted in an
      increase in spike activity which was concentration dependent, whereas stimulation
      with phosphate-buffered saline and 0.1 mM acetylcholine gave no increase in
      activity. The delay in response was not concentration dependent. The action of
      possible host cues was investigated. Stimulation with heat-inactivated foetal
      calf serum (IFCS) and 10 mM glutathione gave an increase in spike activity but
      exposure to 5 mg/dl haemoglobin elicited no response. The response to IFCS was
      found to be suppressed completely by pre-incubation for 30 min in ivermectin.

PMID- 11289072
TI  - Immunohistochemical localization and differentiation of phosphocholine-containing
      antigens of the porcine, parasitic nematode, Ascaris suum.
AB  - The glycolipids of Ascaris suum represent either neutral, zwitterionic or acidic
      structures. The acidic fraction comprises a sulphatide and an unusual
      phosphoinositolglycosphingolipid (Lochnit et al. 1998b). The sulphatide was
      previously localized to the hypodermis, contractile zone of somatic muscle cells
      and the external musculature of the female uterus, whereas the presence of the
      phosphoinositolglycosphingolipid species was restricted to the intestine. The
      neutral and zwitterionic components belong to the arthro-carbohydrate series,
      which are substituted in their zwitterionic structures by phosphocholine (PC) and
      in one glycolipid by an additional phosphoethanolamine residue. In previous
      immunohistochemical localization studies, however, the chemical nature of the PC
      substituted biomolecules has not been investigated in detail. Here, we report on
      the immunohistochemical localization and differentiation of phosphocholine
      containing structures into lipid- and protein-bound species in adult A. suum. The
      patterns of immunostaining, obtained with a PC-specific monoclonal antibody and
      anti-zwitterionic glycolipid hyperimmune serum in the female worm, indicated a
      parallel organ distribution for glycolipid- and protein-bound PC-epitopes.
      Immunoreactivity was localized to specific tissues of the body wall, intestine
      and reproductive tract. This is the first report of surface-located PC-epitopes
      for ascarids. The patterns of immunolabelling obtained with antibodies directed
      against the unsubstituted arthro-carbohydrate series backbone suggested that the
      glycolipid-bound epitope was restricted to the hypodermis, whilst the protein
      bound antigenic determinant resembled that for PC.

PMID- 11289073
TI  - Cloning and expression of cystatin, a potent cysteine protease inhibitor from the
      gut of Haemonchus contortus.
AB  - A cDNA encoding a cysteine protease inhibitor (cystatin) was identified by
      immunoscreening a Haemonchus contortus cDNA library with antisera from lambs
      vaccinated with a protective membrane protein complex (H-gal-GP) derived from the
      gut of the parasite. The cDNA sequence, designated Cys-1, showed significant
      levels of similarity with cystatins from several species of nematode as well as
      with human cystatin. Recombinant H. contortus cystatin was expressed in
      Escherichia coli in a soluble and functionally active form, which proved to be a
      potent inhibitor of both mammalian cathepsin B and native H. contortus cysteine
      proteases. Immunolocalization studies using antisera raised against recombinant
      H. contortus cystatin showed that the inhibitor was predominantly expressed in
      the cytoplasm of intestinal cells. To determine whether H. contortus had any
      protective capacity against infection, lambs were vaccinated with the recombinant
      molecule and subsequently given a single challenge infection. Although
      vaccination did not confer any protection against infection with H. contortus, as
      judged by faecal egg output or worm counts, cystatin will be a valuable tool in
      the analysis of the function of the cysteine proteases which are the subject of
      on-going study as potential vaccine components.

PMID- 11289074
TI  - A comparative molecular field analysis of cytochrome P450 2A5 and 2A6 inhibitors.
AB  - Structure-activity relationships of 23 P450 2A5 and 2A6 inhibitors were analysed
      using the CoMFA and GOLPE/GRID with smart region definition (SRD). The predictive
      power of the resulting models was validated using five compounds not belonging to
      the model set. All models have high internal and external predictive power and
      resulting 3D-QSAR models are supporting each other. Both Sybyl and GOLPE
      highlight properties near lactone moiety to be important for 2A5 and 2A6
      inhibition. Another important feature for pIC50 was the size of the substituent
      in the 7-positon of coumarin. The models suggest that the 2A5 binding site is
      larger that that of 2A6 due to larger steric regions in the CoMFA coefficient
      maps and corresponding GOLPE maps. In addition, the maps reveal that 2A6
      disfavours negative charge near the lactone moiety of coumarin.

PMID- 11289075
TI  - QSAR study and VolSurf characterization of anti-HIV quinolone library.
AB  - Antiviral quinolones are promising compounds in the search for new
      therapeutically effective agents for the treatment of AIDS. To rationalize the
      SAR for this new interesting class of anti-HIV derivatives, we performed a 3D
      QSAR study on a library of 101 6-fluoro and 6-desfluoroquinolones, taken either
      from the literature or synthesized by us. The chemometric procedure involved a
      fully semiempirical minimization of the molecular structures by the AMSOL
      program, which takes into account the solvatation effect, and their 3D
      characterization by the VolSurf/GRID program. The QSAR analysis, based on PCA and
      PLS methods, shows the key structural features responsible for the antiviral
      activity.

PMID- 11289076
TI  - A multivariate insight into the in vitro antitumour screen database of the
      National Cancer Institute: classification of compounds, similarities among cell
      lines and the influence of molecular targets.
AB  - A multivariate insight into the in vitro antitumour screen database of the NCI by
      means of the SIMCA package allows to propose hypotheses on the mechanism of
      action of novel anticancer compounds. As an example, the application of
      multivariate analysis to the NCI standard database provided clues to the
      classification of drugs whose mechanism is either unknown or controversial.
      Moreover, the influence of intrinsic biochemical cell line properties (molecular
      targets) on the sensitivity to drug treatment could be evaluated simultaneously
      for classes of compounds which act by the same mechanism. Interestingly, the
      present approach can also provide a correlation between the molecular targets and
      the therapeutical fingerprint of novel active compounds thus suggesting specific
      biochemical studies for the investigation of new mechanisms of drug action and
      resistance. The statistical approach reported here represents a valuable tool for
      handling theenormous data sets deriving from recent genome-wide investigations of
      gene expression in the NCI cell lines.

PMID- 11289077
TI  - Force-field parametrization and molecular dynamics simulations of p-menthan-3,9
      diols: a family of amphiphilic compounds derived from terpenoids.
AB  - A set of amphiphilic p-menthan-3,9-diols have been investigated by molecular
      dynamics simulations. These are four stereoisomers than can be specifically
      obtained from two terpenoids widely used in biorganic chemistry. For this
      purpose, the p-menthan-3,9-diols have been explicitly parametrized using both
      semiempirical and ab initio quantum mechanical calculations. The reliability of
      these parameters has been validated by predicting different molecular and
      thermodynamic properties. Molecular dynamics simulations in aqueous solution have
      been performed with the new parameters. The results provide useful insights about
      the conformational properties of this family of compounds and the formation of
      intra- and intermolecular hydrogen bonds.

PMID- 11289078
TI  - An improved nicotinic pharmacophore and a stereoselective CoMFA-model for
      nicotinic agonists acting at the central nicotinic acetylcholine receptors
      labelled by.
AB  - A study of a series of compounds with agonistic effect at the alpha4beta2
      nicotinic acetylcholine receptors resulted in an improved pharmacophore model as
      well as a CoMFA model. The pharmacophore was composed of three pharmacophoric
      elements: (1) a site point (a) corresponding to a protonated nitrogen atom, (2) a
      site point (b) corresponding to an electronegative atom capable of forming a
      hydrogen bond, and (3) the centre of a heteroaromatic ring or a C=O bond (c). The
      pharmacophoric elements were related by the following parameters: (a-b) 7.3-8.0
      A, (a-c) 6.5-7.4 A, and the angle between the two distance vectors (delta bac)
      30.4-35.8 degrees. In addition to this, a stereoselective CoMFA model was
      developed, which showed good predictability even for compound classes not present
      in the training set.

PMID- 11289079
TI  - Conformational study of insect adipokinetic hormones using NMR constrained
      molecular dynamics.
AB  - Mem-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asp-Trp-NH2), Tem-HrTH (pGlu-Leu-Asn-Phe-Ser-Pro
      Asn-Trp-NH2) and Del-CC (pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp-Gly-Asn-NH2) are
      adipokinetic hormones, isolated from the corpora cardiaca of different insect
      species. These hormones regulate energy metabolism during flight and so are
      intimately involved in an insect's mobility. Secondary structural elements of
      these peptides and the N7 analogue, [N7]-Mem-CC (pGlu-Leu-Asn-Tyr-Ser-Pro-Asn-Trp
      NH2), have been determined in dimethylsulfoxide solution using NMR restrained
      molecular mechanic simulations. The neuropeptides were all found to have an
      extended structure for the first 4 residues and a beta-turn between residues 4-8.
      For Tem-HrTH and Del-CC, asparagine (N7) which is postulated to be involved in
      receptor binding and/or activation, projects outward form the beta-turn. Mem-CC
      does not have an asparagine at position 7 while, for [N7]-Mem-CC, the N7
      sidechain folds inside the beta-turn preventing its interaction with the
      receptor.

PMID- 11289080
TI  - Lipophilicity in PK design: methyl, ethyl, futile.
AB  - Lipophilicity, often expressed as distribution coefficients (log D) in
      octanol/water, is an important physicochemical parameter influencing processes
      such as oral absorption, brain uptake and various pharmacokinetic (PK)
      properties. Increasing log D values increases oral absorption, plasma protein
      binding and volume of distribution. However, more lipophilic compounds also
      become more vulnerable to P450 metabolism, leading to higher clearance. Molecular
      size and hydrogen bonding capacity are two other properties often considered as
      important for membrane permeation and pharmacokinetics. Interrelationships among
      these physicochemical properties are discussed. Increasing size (molecular
      weight) often gives higher potency, but inevitably also leads to either higher
      lipophilicity, and hence poorer dissolution/solubility, or to more hydrogen
      bonding capacity, which limits oral absorption. Differences in optimal properties
      between gastrointestinal absorption and uptake into the brain are addressed.
      Special attention is given to the desired lipophilicity of CNS drugs. In examples
      using beta-blockers, Ca channel antagonists and peptidic renin inhibitors we will
      demonstrate how potency and pharmacokinetic properties need to be balanced.

PMID- 11289081
TI  - Cyclobenzaprine hydrochloride is a commonly prescribed centrally acting muscle
      relaxant, which is structurally similar to tricyclic antidepressants (TCAs) and
      differs from amitriptyline by only one double bond.

PMID- 11289082
TI  - A four-category verbal rating scale (VRS-4), an 11-point numeric rating scale
      (NRS-11), and a 100-mm visual analog scale (VAS) were compared in the assessment
      of acute pain after oral surgery.

PMID- 11289083
TI  - Referred muscle pain: basic and clinical findings.

PMID- 11289084
TI  - The peripheral apparatus of muscle pain: evidence from animal and human studies.
AB  - The peripheral apparatus of muscle pain consists of nociceptors that can be
      excited by endogenous substances and mechanical stimuli. Histologically, the
      nociceptors are free nerve endings supplied by group III (thin myelinated) and
      group IV (nonmyelinated) afferents with conduction velocities less than 30 m/s.
      At the molecular level, nociceptors have receptors for algesic substances, such
      as bradykinin, serotonin, and prostagladin E2. The purinergic receptors and
      tetrodotoxin-resistant sodium channels might be new important targets for the
      treatment of muscle pain. Algesic substances (capsaicin, bradykinin, serotonin,
      potassium chloride, and hypertonic saline) and other stimuli (ischemia, strong
      mechanical stimuli, and electrical stimuli) have been shown to induce nociception
      from muscle in animals and muscle pain in humans. Muscle nociceptors can be
      sensitized to chemical and mechanical stimuli. Contrary to a former belief, the
      sensitization is not an unspecific process; rather, it is caused by endogenous
      algesic substances binding to highly specific receptor molecules in the membrane
      of the nociceptive ending. For example, animal studies showed that serotonin
      sensitizes muscle nociceptors to chemical and mechanical stimuli. Later, human
      studies showed that serotonin combined with bradykinin induces muscle
      hyperalgesia to pressure. The sensitization process by endogenous substances that
      are likely to be released during trauma or inflammatory injury is probably the
      best established peripheral mechanism for muscle tenderness and hyperalgesia.

PMID- 11289085
TI  - Sex differences in musculoskeletal pain.
AB  - Epidemiologic, clinical, and experimental evidence points to sex differences in
      musculoskeletal pain. Adult women more often have musculoskeletal problems than
      do men. Discrepant findings regarding the presence of such differences during
      childhood and adolescence continue. Biologic and psychosocial factors might
      account for these differences. The authors review evidence showing that
      mechanically induced pressure is more likely to show sex differences than other
      noxious stimuli and to discriminate between individuals suffering from
      musculoskeletal pain and matched controls. The authors suggest that a state of
      increased pain sensitivity, with a peripheral or central origin, predisposes
      individuals to chronic muscle pain conditions, and that there are sex differences
      in the operation of these mechanisms; women are vulnerable to the development and
      maintenance of musculoskeletal pain conditions.

PMID- 11289086
TI  - Pharmacologic pain treatment of musculoskeletal disorders: current perspectives
      and future prospects.
AB  - OBJECTIVE: The authors aimed to provide an educational update on the current
      evidence of the effectiveness of drug therapy in the treatment of musculoskeletal
      pain and to offer a perspective of possible future developments. DESIGN: The
      authors used a pragmatic review of data provided by available systematic reviews
      and seminal controlled studies pertaining to the treatment of regional
      musculoskeletal pain problems. RESULTS: Epidural steroids may offer limited,
      short-term benefit for sciatica. Local injections of steroids are either
      ineffective or provide short-lasting benefits. Nonsteroidal anti-inflammatory
      drugs and opioids reduce pain, but the effect size is modest. The literature does
      not support convincingly the use of antidepressants. Certain muscle relaxants may
      be useful in the treatment of back pain. Hyaluronic acid, neutraceutical agents,
      avocado-soybean unsaponifiable agents, oxaceprol and diacerein may be effective
      in the treatment of osteoarthritis, but the information regarding these new
      agents does not allow wholesale endorsement of these substances. Selective
      epidural injection of steroids at a target nerve root approached through the
      intervertebral foramin has the potential to replace the traditional epidural
      approach. Long-acting, C--fiber-specific local anesthetics are under
      investigation and could provide long-lasting pain relief without motor or sensory
      impairment. In the future, central hypersensitivity in chronic musculoskeletal
      pain might be treated using antagonists of the N-methyl-D-aspartate receptor.
      Cannabinoid agents produce antinociception and prevent experimentally induced
      hyperalgesia in animals, and they may find a role in pain management. Methods to
      optimize drug combinations are available. CONCLUSIONS: The effectiveness of the
      currently available drugs in the treatment of musculoskeletal pain conditions is
      disappointing. Recent developments may open new perspectives in this area of pain
      medicine.

PMID- 11289087
TI  - Nonpharmacological treatments for musculoskeletal pain.
AB  - BACKGROUND: Several types of physical therapy are used in the management of
      painful musculoskeletal disorders. These treatment modalities can be broadly
      categorized as electrotherapy modalities (e.g., transcutaneous electrical nerve
      stimulation), acupuncture, thermal modalities (e.g., moist heat, ultrasound),
      manual therapies (e.g., manipulation or massage), or exercise. Within each of
      these broad categories significant variations in treatment parameters are
      possible. OBJECTIVE: To consider the evidence base for each of these main
      categories of physical therapy in the management of musculoskeletal pain. METHOD:
      To consider the available evidence related to clinical effectiveness and then to
      review evidence from basic science studies evaluating potentially therapeutic
      effects of the various therapies. RESULTS: There seems to be evidence from basic
      science research to suggest that many of the therapies could have potentially
      therapeutic effects. However, there appears to be limited high-quality evidence
      from randomized clinical trials to support the therapeutic effectiveness of
      several of the therapies. CONCLUSIONS: There is some preliminary evidence to
      support the use of manual therapies, exercise, and acupuncture in the management
      of some categories of musculoskeletal pain. Limitations of the existing research
      base are discussed and recommendations for areas of future research are provided.

PMID- 11289088
TI  - Temporomandibular joint pain analgesia by linearly polarized near-infrared
      irradiation.
AB  - OBJECTIVE: The objective of this study was to describe a pilot treatment of
      temporomandibular joint pain by linearly polarized near-infrared irradiation.
      DESIGN: A prospective clinical study. SETTING: University teaching hospital.
      PATIENTS: Patients comprised 20 women (mean age +/- SD: 26.6 +/- 15.2 years) with
      unilateral temporomandibular pain. The patients had already received other
      conservative treatments, but temporomandibular pain did not attenuate.
      INTERVENTION: Linearly polarized near-infrared irradiation with the Super Lizer
      was used. RESULTS: The painless interincisal distance of the mouth opening, which
      is one of the objective parameters of temporomandibular dysfunction, and the
      visual analogue scale of the affected temporomandibular joint before treatment
      were 33.4 +/- 6.5 mm and 5.0 +/- 2.7 points, respectively. Pilot linearly
      polarized near-infrared irradiation was applied weekly to the skin areas
      overlying four painful points. The present treatment alleviated temporomandibular
      pain after the patients had received only four weekly irradiation treatments,
      with final measured values of the visual analogue scale being 1.4 +/- 1.6 points.
      The final painless mouth-opening distance increased by 7.6 +/- 4.6 mm compared
      with the first measured distance without complications. CONCLUSION: This pilot
      treatment using the Super Lizer provided relief from temporomandibular pain over
      a period of 4 weeks.

PMID- 11289089
TI  - Theoretical perspectives on the relation between catastrophizing and pain.
AB  - The tendency to "catastrophize" during painful stimulation contributes to more
      intense pain experience and increased emotional distress. Catastrophizing has
      been broadly conceived as an exaggerated negative "mental set" brought to bear
      during painful experiences. Although findings have been consistent in showing a
      relation between catastrophizing and pain, research in this area has proceeded in
      the relative absence of a guiding theoretical framework. This article reviews the
      literature on the relation between catastrophizing and pain and examines the
      relative strengths and limitations of different theoretical models that could be
      advanced to account for the pattern of available findings. The article evaluates
      the explanatory power of a schema activation model, an appraisal model, an
      attention model, and a communal coping model of pain perception. It is suggested
      that catastrophizing might best be viewed from the perspective of hierarchical
      levels of analysis, where social factors and social goals may play a role in the
      development and maintenance of catastrophizing, whereas appraisal-related
      processes may point to the mechanisms that link catastrophizing to pain
      experience. Directions for future research are suggested.

PMID- 11289090
TI  - Pain-related catastrophizing: what is it?
AB  - Progress in advancing understanding of the role of "catastrophizing" in pain and
      associated physical and psychosocial disability may be furthered by (1)
      consideration of the construct of catastrophizing, (2) evaluation of the extent
      to which currently available measures of pain catastrophizing tap into that
      construct, (3) investigation of the relation of catastrophizing to personal trait
      variables (e.g., neuroticism and worry), and (4) identification of the conditions
      (or states) under which catastrophizing is most likely to occur. In this article,
      the authors discuss these issues and suggest directions for future research.

PMID- 11289092
TI  - International Headache Society headache diagnostic patterns in pain facility
      patients.
AB  - OBJECTIVE: Previous studies have indicated that many patients with chronic pain
      (PWCP) referred to pain facilities for the treatment of neck and/or low back pain
      complain of associated headaches. The purpose of this study was to characterize
      the nature of these headaches according to International Headache Society (IHS)
      headache diagnostic criteria. DESIGN: In preparation for this study, a
      questionnaire that reflected IHS headache diagnostic criteria was developed. All
      consecutive patients admitted to our pain facility complaining of headache
      completed this questionnaire and received a physical and neurologic examination
      focused on key aspects of headache. A headache interview was also conducted,
      using the questionnaire as a question guide. All questionnaires were entered in a
      computerized database, and IHS diagnoses were arrived at for each patient. As
      many IHS diagnoses as possible were assigned to each PWCP as long as IHS criteria
      were fulfilled. In addition, a frequency distribution for headache precipitants
      and neck-associated symptoms was developed and evaluated by discriminant analysis
      to determine the diagnostic value of these factors in relation to each IHS
      diagnostic group. SETTING: Pain facility (multidisciplinary pain center).
      PATIENTS: Consecutive PWCP. RESULTS: Of 1,466 PWCP, 154 (10.5%) were identified
      as suffering from severe headache interfering with function. Of these, 55.8%
      indicated that their headaches were related to an injury for which they were
      seeking treatment and 83.7% had neck pain. Migraine headache represented the most
      common diagnostic group (90.3%), with cervicogenic headache representing the
      second most common (33.8%). Of the total group, 44.2% had more than one headache
      diagnosis, that is, there was overlap. Cervicogenic headache patients had the
      greatest percentage of overlap (94.2%), with migraine patients being second
      (68.3%). The most frequent headache precipitant was mental stress, followed by
      neck position and activity/exercise. The migraine and cervicogenic headache
      groups had a statistically significant greater number of neck-associated symptoms
      when compared with the remaining patients. Of the total headache group, 74.6%
      complained that they had a tender point at the back of their neck. Cervicogenic,
      migraine, and tension PWCP had the greatest frequency of head or neck tender
      points. The discriminant analysis for neck-associated symptoms yielded the
      following symptoms as the most common predictors of headache across IHS
      diagnostic groups: clues to onset were severe headache beginning at the neck or
      tender point and numbness in arms and legs; headache brought on by neck position
      and arms overhead; and neck symptoms consisting of a tender point in the neck and
      feeling severe headache in the neck. CONCLUSIONS: Headache can and should be
      considered a frequent comorbid condition in PWCP. Because of the overlap data,
      more precise diagnostic criteria may be required to separate cervicogenic
      headache from migraine headache. Neck-associated symptoms seem to be important
      even to those PWCP diagnosed with migraine headache.

PMID- 11289091
TI  - Plasma levels of interleukin-6 and interleukin-10 are affected by ketorolac as an
      adjunct to patient-controlled morphine after abdominal hysterectomy.
AB  - OBJECTIVE: Because morphine affects various immune functions, patient-controlled
      analgesia with morphine may further deteriorate the immune mechanisms after
      surgery. Therefore, the purpose of this study was to determine differences
      between morphine patient-controlled analgesia and a combination of morphine and
      ketorolac in interleukin-6 and interleukin-10 responses, and in analgesia and
      morphine-related side effects. DESIGN: Prospective study. PATIENTS: Twenty-two
      patients who underwent abdominal hysterectomy were classified randomly into two
      groups: (1) patient-controlled analgesia with morphine; and (2) patient
      controlled analgesia with a combination of morphine and ketorolac. Blood samples
      to measure cytokines were collected at preoperatively, immediately
      postoperatively, and 2 hours, 4 hours, and 24 hours postoperatively. OUTCOME
      MEASURES: Plasma was separated and frozen until the analysis of cytokines using
      enzyme-linked immunosorbent assays. Postoperative pain was assessed using a
      visual analog score. Sedation was checked based on a protocol developed at the
      Samsung Medical Center. RESULTS: In the two groups, interleukin-6 increased
      immediately postoperatively, and it remained consistent for 24 hours. Interleukin
      10 concentrations peaked at 2 hours postoperatively and progressively decreased.
      Cytokine concentrations between the two groups were significantly different for
      interleukin-6 24 hours postoperatively (p = 0.026) and for interleukin-10 4 hours
      postoperatively (p = 0.045). Total analgesic use was not different, but morphine
      consumption was significantly different (p = 0.037 at 4 hours postoperatively, p
      = 0.015 at 24 hours postoperatively). Pain scores, sedation, and side effects
      were unaffected by the patient-controlled analgesia regimen. CONCLUSIONS: The
      authors conclude that supplementation using ketorolac plus administration of
      morphine modifies cytokine responses and may contribute to immune augmentations
      during postoperative periods.

PMID- 11289093
TI  - Clinical and physiologic evaluation of stellate ganglion blockade for complex
      regional pain syndrome type I.
AB  - OBJECTIVE: The efficacy of peripheral sympathetic interruption after stellate
      ganglion blockade was assessed by a sympathetic function test. Results were
      compared with clinical signs such as temperature changes, pain reduction, and the
      development of Horner syndrome to evaluate the correlation with clinical
      investigations. DESIGN: Stellate ganglion blockade with local anesthetics was
      carried out via an anterior paratracheal approach in 33 patients suffering from
      complex regional pain syndrome type I. Patients were examined before and after
      the procedure. For assessment of sympathetic nervous function, the
      vasoconstrictor response to sympathetic stimuli was assessed using laser Doppler
      flowmetry. Clinical parameters like surface temperature changes (thermography),
      pain relief (visual analogue scale), and Horner syndrome were monitored. RESULTS:
      Twenty-three (70%) of 33 patients developed an increase in temperature difference
      between the treated hand and the contralateral hand of more than 1.5 degreesC
      after the procedure, which is a clinical sign of sympathicolysis. In 48% (n = 11)
      of these patients, the sympathetic function test showed an undisturbed
      sympathetic nervous function. In 10 patients, no significant increase in
      temperature difference was observed. Although these patients presented with a
      normal sympathetic vasoconstrictor response, 4 felt pain relief of more than 50%,
      suggesting a placebo effect. Only 7 patients with pain relief revealed both
      clinical sympathicolysis and extinguished sympathetic nervous function and
      qualified for sympathetically maintained pain. CONCLUSIONS: Clinical
      investigation is not reliable in the assessment of stellate ganglion blockade.
      Proof of sympathetically maintained pain based on pain relief after stellate
      ganglion blockade is not conclusive.

PMID- 11289094
TI  - The BCR gene and philadelphia chromosome-positive leukemogenesis.

PMID- 11289095
TI  - Human papillomavirus type 16 E7 oncoprotein-induced abnormal centrosome synthesis
      is an early event in the evolving malignant phenotype.
AB  - Genomic instability is a hallmark of malignant growth that frequently involves
      mitotic defects associated with centrosome abnormalities. However, the question
      of whether abnormal centrosomes cause genomic instability or develop secondary to
      other changes has not been conclusively resolved. Here we show that human
      papillomavirus (HPV)-16 E7 can induce abnormal centrosome synthesis before the
      development of extensive nuclear abnormalities. In contrast, expression of HPV-16
      E6 is associated with marked nuclear atypia and concomitant accumulation of
      centrosomes. Our results demonstrate that HPV-16 E7-induced centrosome
      abnormalities represent an early event during neoplastic progression potentially
      driving genomic destabilization.

PMID- 11289096
TI  - Invasion activating caveolin-1 mutation in human scirrhous breast cancers.
AB  - We looked for mutations in the caveolin-1 gene, encoding a critical molecule for
      membrane signaling to cell growth, in 92 primary human breast cancers, and we
      report here the identification of a mutation in caveolin-1 at codon 132 (P132L)
      in 16% of cases. The mutation-positive cases were mostly invasive scirrhous
      carcinomas. In cell lines expressing the same mutant of caveolin-1, we observed
      that the mutant Caveolin-1 expression seemed to induce cellular transformation
      and activation of mitogen-activated protein kinase-signaling pathway and to
      promote invasion-ability as well as altered actin networks in the cells. These
      results provide, for the first time, genetic evidence that a functioning Caveolin
      1 mutation may have a role in the malignant progression of human breast cancer.

PMID- 11289097
TI  - Stimulation of mammary tumorigenesis by systemic tissue inhibitor of matrix
      metalloproteinase 4 gene delivery.
AB  - Tissue inhibitors of matrix metalloproteinase (TIMPs) are multifunctional
      proteins with both matrix metalloproteinase (MMP) inhibitory effects and growth
      regulatory activity. TIMPs inhibit MMP activity, suggesting a use for cancer gene
      therapy. However, here we report that systemic administration of human TIMP-4 by
      electroporation-mediated i.m. injection of naked TIMP-4 DNA stimulates
      tumorigenesis of human breast cancer cells in nude mice. Consistent with tumor
      stimulation, TIMP-4 up-regulates Bcl-2 and Bcl-X(L) protein. TIMP-4 also inhibits
      apoptosis in human breast cancer cells in vitro and mammary tumors in vivo. A
      synthetic MMP inhibitor BB-94 did not have such antiapoptotic effect. Analysis of
      TIMP-4 expression in human mammary specimens indicates that TIMP-4 protein is
      increased in mammary carcinoma cells compared with normal mammary epithelial
      cells. These data indicate an antiapoptotic activity in breast cancer cells and a
      tumor-stimulating effect of TIMP-4 when administrated systemically.

PMID- 11289098
TI  - Patterns of CDKN2A gene loss in sequential oral epithelial dysplasias and
      carcinomas.
AB  - The CDKN2A gene locus encodes two different proteins derived from alternative
      splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and
      p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53.
      Inactivation of p16 is a common finding in many cancers; however, there is little
      data on CDKN2A gene abnormalities in oral precancer. In this longitudinal study,
      we examined changes in the CDKN2A gene locus in sequential epithelial dysplasias
      and oral carcinomas from 11 patients. Genomic DNA was extracted from laser
      microdissected lesional tissue, and exons 1alpha, 1beta, and 2 were analyzed by
      duplex PCR. Immunohistochemistry was done to identify p16 and p14ARF protein
      expression. Two adjacent polymorphic microsatellite markers were used for
      allelotyping. Homozygous deletion of exon 1alpha was identified in 2 of 17 (12%)
      precancerous lesions. Loss of either exon 1alpha, exon 2, or both was seen in
      seven of nine (78%) carcinomas. In five of these carcinomas, there was loss of
      only exon 1alpha. No case showed deletion of exon 1beta. In 5 of 11 patients,
      microsatellite markers showed differing patterns of allelic imbalance in the
      precancerous lesions and the subsequent carcinoma, suggesting a complex genetic
      pattern of progression from dysplasia to carcinoma. We conclude that during oral
      carcinogenesis homozygous deletion of exon 1alpha of the CDKN2A gene is common
      but that deletion of exon 2 and 1beta is less frequent. Moreover, our results
      suggest that the progression from oral precancer to cancer, in some cases, is
      more complex genetically than predicted by linear models of carcinogenesis.

PMID- 11289099
TI  - A novel alternative approach for prediction of radiation response of squamous
      cell carcinoma of head and neck.
AB  - Accurate prediction of human tumor response to radiation therapy and concomitant
      chemoradiation would be an important tool to assist the physician in making
      recommendations for tumor treatment. Most of the studies that define the
      molecular markers for prediction of radiation response are based on the
      observation of gene expression using immunostaining, Northern blot, or Western
      blot analysis of a single or several genes. The results vary among different
      studies, and some results are contradictory. However, the studies agree that the
      change in expression of the tumor-related gene affects the radiation response. In
      this study, we explored a novel approach to predict the radiation response of
      human tumor using Atlas human cancer 1.2 cDNA array to analyze the expression
      profile of 1187 tumor-related genes in radiation-resistant and radiation
      sensitive tissues. Sixty tumor-related genes were selected as predictors of
      radiation response of squamous cell carcinoma of the head and neck. Using the
      expression intensity of these 60 tumor-related genes, in combination with cluster
      analysis, we successfully predicted the radiation identity of two tumor samples.

PMID- 11289100
TI  - A case-control study of microsomal epoxide hydrolase, smoking, meat consumption,
      glutathione S-transferase M3, and risk of colorectal adenomas.
AB  - We estimated associations between polymorphisms in the gene encoding microsomal
      epoxide hydrolase (mEH) among 464 cases diagnosed with first occurrence of
      colorectal adenoma and 510 matched controls. In an analysis controlling only for
      the matching variables, we found little or no association between adenoma and mEH
      genotypes defined by polymorphisms at either codon 113 and 139 or mEH activity
      predicted by both polymorphisms. However, in subsequent analyses, high predicted
      mEH activity was significantly associated with adenoma among certain subgroups
      defined by smoking history [odds ratio (OR), 4.27; 95% confidence interval (CI),
      1.68-10.81 among current smokers; interaction, P = 0.11], meat consumption (OR,
      2.47; CI, 0.99-6.19 among individuals who regularly eat well-done meat;
      interaction, P = 0.03), and genotypes for the *A/*B polymorphism in the gene
      encoding glutatione S-transferase M3 (OR, 2.60; CI, 1.28-5.28 among individuals
      with *A*A genotype; interaction, P = 0.03). These findings are consistent with
      causal roles for environmental polycyclic aromatic hydrocarbons and genetically
      encoded variants in enzymes whose actions lead to the production of activated
      polycyclic aromatic hydrocarbon metabolites.

PMID- 11289101
TI  - Protection of mice against leukemia after vaccination with bone marrow-derived
      dendritic cells loaded with apoptotic leukemia cells.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that need
      to be activated before they can function to initiate primary and secondary immune
      responses in vivo. DCs are also specialized to maintain peripheral tolerance to
      self after uptake of apoptotic material, likely corresponding to both apoptotic
      bodies and whole apoptotic cells. Here, we report that murine bone marrow-derived
      DCs can be activated in vitro by exogenous signals received from apoptotic
      leukemia cells expressing on the cell surface a model tumor-associated antigen.
      Injected in vivo, these exogenously activated DCs can function as adjuvants to
      protect mice against leukemia by stimulating an antigen-specific cellular
      mediated cytotoxic immune response. To our knowledge, this is the first report
      indicating that DCs loaded with apoptotic leukemia cells protect mice against
      leukemia development.

PMID- 11289102
TI  - Activated in prostate cancer: a PDZ domain-containing protein highly expressed in
      human primary prostate tumors.
AB  - Critical events in prostate tumorigenesis and metastasis likely include the
      abnormal activation and expression of specific genes. Using RNA expression
      profiling techniques, we have identified a transcript originating from the
      activated in prostate cancer (AIPC) gene, the expression of which is
      preferentially up-regulated in several cultured prostate tumor cell lines and
      human primary prostate tumors. Sequence analysis revealed that the AIPC protein
      encodes six PDZ domains, which are protein-protein binding domains likely
      involved in protein clustering and scaffolding. Immunohistochemical analysis of a
      tissue microarray comprising 158 tumor, 18 high-grade prostatic intraepithelial
      neoplasia, and 91 normal prostate specimens with an anti-AIPC antibody
      demonstrated abundant AIPC protein expression in 75% of tumors, 83% of prostatic
      intraepithelial neoplasia lesions, and 3% of normal tissues (P < 0.0001). These
      data suggest that the accumulation of AIPC protein may be closely associated with
      the initiation or early promotion of prostate tumorigenesis.

PMID- 11289103
TI  - Intestinal microflora are necessary for development of spontaneous adenocarcinoma
      of the large intestine in T-cell receptor beta chain and p53 double-knockout
      mice.
AB  - This study was conducted to confirm the hypothesis that intestinal microflora are
      required for the development of adenocarcinoma in the colon of the TCRbeta and
      p53 double-knockout (TCRbeta-/- p53-/-) mouse. Germ-free TCRbeta-/- p53-/- mice
      were produced. At 7 weeks of age, the animals were divided into two groups (n =
      10/group), and one of these groups was conventionalized. Animals of both groups
      were subjected to histopathological examination for adenocarcinoma of the colon
      at 4 months of age. There was no development of adenocarcinoma of the colon among
      the germ-free mice, whereas in the conventionalized group, adenocarcinomas of the
      ileocecum and cecum were detected in 70% of animals. These results indicate the
      usefulness of the TCRbeta-/- p53-/- mouse as a colon cancer animal model that
      develops spontaneous adenocarcinoma of the colon early in life, and suggest that
      intestinal microflora play a major role in the development of adenocarcinoma of
      the colon in this animal model.

PMID- 11289104
TI  - Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2
      expression in gastric epithelial cells.
AB  - Cyclooxygenase (COX)-2, the inducible form of the rate-limiting enzyme for
      prostaglandin synthesis, is up-regulated in gastrointestinal cancers and is a key
      mediator of epithelial cell growth. Helicobacter pylori is causally linked to
      gastric cancer. In H. pylori gastritis, COX-2 expression localizes to the
      subepithelial region, with variable levels in the epithelium. In contrast, in
      gastric cancer, COX-2 strongly predominates in the epithelium, suggesting that
      the transition to consistent epithelial COX-2 overexpression may be a critical
      molecular event in gastric carcinogenesis. Because aberrant promoter methylation
      inhibits expression of a variety of genes in gastrointestinal cancers, we sought
      to determine whether methylation of the COX-2 promoter could regulate the
      response to H. pylori in gastric epithelial cells. We assessed COX-2 expression
      and promoter methylation status in six gastric epithelial cell lines. In all four
      of the cell lines that exhibited basal expression of COX-2 and a significant
      increase in expression in response to H. pylori, the COX-2 promoter was
      unmethylated, whereas in the two cell lines that did not express COX-2, the COX-2
      promoter was methylated. Treatment of COX-2-methylated cells with the
      demethylating agent 5-azacytidine had a modest effect on COX-2 expression, but
      when 5-azacytidine-treated cells were subsequently stimulated with H. pylori,
      there was a significant, 5-10-fold enhancement of both COX-2 mRNA and protein
      expression and release of the COX-2 product, prostaglandin E2. In contrast, in
      COX-2-expressing cell lines that were unmethylated at the COX-2 promoter, 5
      azacytidine had no effect on H. pylori-stimulated COX-2 expression. These
      findings suggest that loss of COX-2 methylation may facilitate COX-2 expression
      and promote gastric carcinogenesis associated with H. pylori infection.

PMID- 11289105
TI  - Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular
      function and leukocyte recruitment: role of VEGF-receptor 2 and host VEGF-A.
AB  - Unlike vascular endothelial growth factor (VEGF)-A, the effect of VEGF-C on tumor
      angiogenesis, vascular permeability, and leukocyte recruitment is not known. To
      this end, we quantified in vivo growth and vascular function in tumors derived
      from two VEGF-C-overexpressing (VC+) and mock-transfected cell lines (T241
      fibrosarcoma and VEGF-A-/- embryonic stem cells) grown in murine dorsal skinfold
      chambers. VC+ tumors grew more rapidly than mock-transfected tumors and exhibited
      parallel increases in tumor angiogenesis. Furthermore, VEGF-C overexpression
      elevated vascular permeability in T241 tumors, but not in VEGF-A-/- tumors.
      Surprisingly, unlike VEGF-A, VEGF-C did not increase leukocyte rolling or
      adhesion in tumor vessels. Administration of VEGF receptor (VEGFR)-2 neutralizing
      antibody DC101 reduced vascular density and permeability of both VC+ and mock
      transduced T241 tumors. These data suggest that VEGFR-2 signaling is critical for
      tumor angiogenesis and vascular permeability and that VEGFR-3 signaling does not
      compensate for VEGFR-2 blockade. An alternate VEGFR, VEGFR-1 or neuropilin-1, may
      modulate adhesion of leukocytes to tumor vessels.

PMID- 11289106
TI  - BMI-1 gene amplification and overexpression in hematological malignancies occur
      mainly in mantle cell lymphomas.
AB  - The BMI-1 gene is a putative oncogene belonging to the Polycomb group family that
      cooperates with c-myc in the generation of mouse lymphomas and seems to
      participate in cell cycle regulation and senescence by acting as a
      transcriptional repressor of the INK4a/ARF locus. The BMI-1 gene has been located
      on chromosome 10p13, a region involved in chromosomal translocations in infant
      leukemias, and amplified in occasional non-Hodgkin's lymphomas (NHLs) and solid
      tumors. To determine the possible alterations of this gene in human malignancies,
      we have examined 160 lymphoproliferative disorders, 13 myeloid leukemias, and 89
      carcinomas by Southern blot analysis and detected BMI-1 gene amplification (3- to
      7-fold) in 4 of 36 (11%) mantle cell lymphomas (MCLs) with no alterations in the
      INK4a/ARF locus. BMI-1 and p16INK4a mRNA and protein expression were also studied
      by real-time quantitative reverse transcription-PCR and Western blot,
      respectively, in a subset of NHLs. BMI-1 expression was significantly higher in
      chronic lymphocytic leukemia and MCL than in follicular lymphoma and large B cell
      lymphoma. The four tumors with gene amplification showed significantly higher
      mRNA levels than other MCLs and NHLs with the BMI-1 gene in germline
      configuration. Five additional MCLs also showed very high mRNA levels without
      gene amplification. A good correlation between BMI-1 mRNA levels and protein
      expression was observed in all types of lymphomas. No relationship was detected
      between BMI-1 and p16INK4a mRNA levels. These findings suggest that BMI-1 gene
      alterations in human neoplasms are uncommon, but they may contribute to the
      pathogenesis in a subset of malignant lymphomas, particularly of mantle cell
      type.

PMID- 11289107
TI  - Inhibition of vascular endothelial growth factor receptor signaling leads to
      reversal of tumor resistance to radiotherapy.
AB  - Certain refractory neoplasms, such as glioblastoma multiforme (GBM) and melanoma,
      demonstrate a resistant tumor phenotype in vivo. We observed that these
      refractory tumor models (GBM and melanoma) contain blood vessels that are
      relatively resistant to radiotherapy. To determine whether the vascular
      endothelial growth factor receptor-2 (Flk-1/KDR) may be a therapeutic target to
      improve the effects of radiotherapy, we used the soluble extracellular component
      of Flk-1 (ExFlk), which blocks vascular endothelial growth factor binding to Flk
      1 receptor expressed on the tumor endothelium. Both sFlk-1 and the Flk-1-specifc
      inhibitor SU5416 eliminated the resistance phenotype in GBM and melanoma
      microvasculature as determined by both the vascular window and Doppler blood flow
      methods. Human microendothelial cells and human umbilical vein endothelial cells
      showed minimal radiation-induced apoptosis. The Flk-1 antagonists sFlk-1 and
      SU5416 reverted these cell models to apoptosis-prone phenotype. Flk-1 antagonists
      also reverted GBM and melanoma tumor models to radiation-sensitive phenotype
      after treatment with 3 Gy. These findings demonstrate that the tumor
      microenvironment including the survival of tumor-associated endothelial cells
      contributes to tumor blood vessel resistance to therapy.

PMID- 11289108
TI  - Overexpression of HER-2 in ovarian carcinomas.
AB  - The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in
      several types of human carcinomas and provides an attractive therapeutic target.
      Shown by immunohistology, <25% of newly diagnosed ovarian carcinomas express the
      HER-2 protein. However, now we report that this protein was expressed in all 20
      tumor cell lines derived from stage III and IV ovarian cancers as well as in
      tumor cells harvested from patients with malignant ascites and in tumor samples
      taken at a second surgery, suggesting that cells with excess expression may have
      a selective growth advantage. HER-2-positive ovarian carcinoma cells were shown
      to be sensitive to antibody-dependent cellular cytotoxicity, and their in vitro
      proliferation was inhibited by anti-HER-2 MAb Herceptin. We postulate, therefore,
      that therapy which targets HER-2 may be more efficacious in patients with ovarian
      carcinoma than indicated by the commonly low expression of HER-2 in tumors
      removed at the time of primary surgery.

PMID- 11289109
TI  - Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit
      chemically induced colitis and formation of aberrant crypt foci in rats.
AB  - The biological role of the peroxisome proliferator-activated receptors (PPARs) in
      various diseases, including inflammation and cancer, has been highlighted
      recently. Although PPARgamma ligands have been found to inhibit mammary
      carcinogenesis in rodents, the effects on colon tumorigenesis are controversial.
      In the present study, three different experiments were conducted to investigate
      the modifying effects of PPARs ligands (PPARalpha and PPARgamma) on colitis and
      an early phase of colitis-related colon carcinogenesis in male F344 rats. In the
      first experiment, gastric gavage of troglitazone (PPARgamma ligand, 10 or 100
      mg/kg body weight) or bezafibrate (PPARalpha ligand, 10 or 100 mg/kg body weight)
      inhibited colitis induced by dextran sodium sulfate (DSS) and lowered trefoil
      factor-2 content in colonic mucosa. In the second experiment, dietary
      administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4
      weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20
      mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor
      lesions for colon carcinoma. In the third experiment, dietary administration
      (0.01% in diet for 6 weeks) of pioglitazone (PPARgamma ligand), troglitazone, and
      bezafibrate effectively suppressed DSS/AOM-induced ACF. Administration of both
      ligands significantly reduced cell proliferation activity in colonic mucosa
      exposed to DSS and AOM. Our results suggest that synthetic PPARs ligands
      (PPARalpha and PPARgamma) can inhibit the early stages of colon tumorigenesis
      with or without colitis.

PMID- 11289110
TI  - Hypoxia activates a platelet-derived growth factor receptor/phosphatidylinositol
      3-kinase/Akt pathway that results in glycogen synthase kinase-3 inactivation.
AB  - Hypoxia initiates numerous intracellular signaling pathways important in
      regulating cell proliferation, differentiation, and death. In this study, we
      investigated the pathway that hypoxia uses to activate Akt and inactivate
      glycogen synthase kinase-3 (GSK-3), two proteins the functions of which are
      important in cell survival and energy metabolism. Severe hypoxia (0.01% oxygen)
      initiated a signaling cascade by inducing the tyrosine phosphorylation of the
      platelet-derived growth factor (PDGF) receptor within 1 h of treatment and
      increasing receptor association with the p85 subunit of phosphatidylinositol 3
      kinase (PI 3-K). Hypoxia-induced signaling also resulted in PI 3-K-dependent
      phosphorylation of Akt on Ser-473, a modification of Akt that is important for
      its activation. This activation of Akt by hypoxia was substantially diminished in
      cells that possessed mutations in their PDGF receptor-PI 3-K interaction domain.
      In addition, Akt activation by hypoxia was resistant to treatment with the growth
      factor receptor poison suramin but was sensitive to treatment with the PI 3-K
      inhibitor wortmannin. Activation of Akt by hypoxia resulted in the
      phosphorylation of GSK-3alpha and GSK-3beta at Ser-9 and Ser-21, two well
      documented Akt phosphorylation sites, respectively, that are inactivating
      modifications of each GSK-3 isoform. In support of the phosphorylation data, GSK
      3 activity was significantly reduced under hypoxia. In conclusion, we propose
      that hypoxia activates a growth factor receptor/PI 3-K/Akt cascade that leads to
      GSK-3 inactivation, a pathway that can impact cell survival, proliferation, and
      metabolism.

PMID- 11289111
TI  - RGD-Tachyplesin inhibits tumor growth.
AB  - Tachyplesin is an antimicrobial peptide present in leukocytes of the horseshoe
      crab (Tachypleus tridentatus). In this study, a synthetic tachyplesin conjugated
      to the integrin homing domain RGD was tested for antitumor activity. The in vitro
      results showed that RGD-tachyplesin inhibited the proliferation of both cultured
      tumor and endothelial cells and reduced the colony formation of TSU prostate
      cancer cells. Staining with fluorescent probes of FITC-annexin V, JC-1, YO-PRO-1,
      and FITC-dextran indicated that RGD-tachyplesin could induce apoptosis in both
      tumor and endothelial cells. Western blotting showed that treatment of cells with
      RGD-tachyplesin could activate caspase 9, caspase 8, and caspase 3 and increase
      the expression of the Fas ligand, Fas-associated death domain, caspase 7, and
      caspase 6, suggesting that apoptotic molecules related to both mitochondrial and
      Fas-dependent pathways are involved in the induction of apoptosis. The in vivo
      studies indicated that the RGD-tachyplesin could inhibit the growth of tumors on
      the chorioallantoic membranes of chicken embryos and in syngenic mice.

PMID- 11289112
TI  - Tyrosine kinase-dependent, phosphatidylinositol 3'-kinase, and mitogen-activated
      protein kinase-independent signaling pathways prevent lung adenocarcinoma cells
      from anoikis.
AB  - Normal epithelial cells are anchorage-dependent. Detachment of normal epithelial
      cells from their substratum causes apoptosis, termed anoikis. Malignant tumor
      cells, however, can survive and proliferate independent of anchorage. To
      understand the molecular basis of tumor cell anchorage independence, we
      investigated the role of tyrosine kinases and their downstream signaling pathways
      in anoikis resistance of human lung adenocarcinoma cells. Four of the five lung
      adenocarcinoma cell lines analyzed are resistant to anoikis. Tyrosine kinase
      inhibitor genistein rendered three of them sensitive to anoikis. Although cell
      detachment induced rapid protein tyrosine dephosphorylation in Madin-Darby canine
      kidney cells, a nontransformed epithelial cell line, tyrosine phosphorylation of
      several proteins in the tumor cells is anchorage-independent. Similarly,
      phosphorylation of Akt and mitogen-activated protein kinase, two signaling
      proteins downstream of tyrosine kinases, was decreased in Madin-Darby canine
      kidney cells but increased in some of the tumor cells upon cell detachment.
      Inhibition of phosphorylation of the two proteins, however, did not induce
      anoikis in the tumor cells. Specific inhibitors to several known tyrosine kinases
      also failed to induce anoikis in these cells. These data suggest the existence of
      tyrosine kinase-dependent phosphatidylinositol 3'-kinase and mitogen-activated
      protein kinase-independent signaling pathways that function to regulate cell
      survival and death. Alteration in these pathways may count for the anchorage
      independent survival of the lung adenocarcinoma cells and other malignant tumor
      cells.

PMID- 11289113
TI  - Cis-polyunsaturated fatty acids stimulate beta1 integrin-mediated adhesion of
      human breast carcinoma cells to type IV collagen by activating protein kinases C
      epsilon and -mu.
AB  - We have investigated the effects of various fatty acids (FAs) on integrin
      mediated MDA-MB-435 breast carcinoma cell adhesion to type IV collagen (collagen
      IV) in vitro. Arachidonic acid (AA) and linoleic acid both induced a dose
      dependent increase in cell adhesion to collagen IV with no significant increase
      in nonspecific adhesion to polylysine and BSA. Oleic acid (a monounsaturated FA),
      AA methyl ester, and linoelaidic acid (a trans-isomer of linoleic acid) failed to
      stimulate adhesion to collagen IV, suggesting that these effects required cis
      polyunsaturation and a free carboxylic moiety and that they were not due to
      membrane perturbations. Calphostin C, a protein kinase C (PKC) inhibitor, blocked
      cis-polyunsaturated FA (cis-PUFA)-induced cell adhesion in a dose-dependent
      manner, suggesting a role for a calcium-dependent PKC in this signal transduction
      pathway. Immunoblotting revealed that cis-PUFAs induced the translocation of
      PKCepsilon and PKCmu, two of the novel PKC isozymes, from the cytosol to the
      membrane. In contrast, a conventional PKC isozyme, PKCalpha, as well as the
      atypical isozymes, PKCzeta and PKCiota, did not translocate after cis-PUFA
      treatment. Function-blocking antibodies specific for alpha1, alpha2, and beta1,
      integrin subunits inhibited cell adhesion to collagen IV, whereas antibodies to
      alpha3 and alpha5 did not. No increase in the expression of these integrins on
      the cell surface was detected after the incubation of cells with cis-PUFAs,
      suggesting that there is an increase in the activity, but not in the amount, of
      these beta1, integrins. Altogether, these data suggest that cis-PUFAs enhance
      human breast cancer cell adhesion to collagen IV by selectively activating
      specific PKC isozymes, which leads to the activation of beta1 integrins.

PMID- 11289114
TI  - Maturation of erythroid cells and erythroleukemia development are affected by the
      kinase activity of Lyn.
AB  - This study examined the impact of the tyrosine kinase Lyn on erythropoietin
      induced intracellular signaling in erythroid cells. In J2E erythroleukemic cells,
      Lyn coimmunoprecipitated with numerous proteins, including SHP-1, SHP-2, ras
      GTPase-activating protein, signal transducers and activators of transcription
      (STAT) 5a, STAT5b, and mitogen-activated protein kinase; however, introduction of
      a dominant-negative Lyn (Y397F Lyn) inhibited the interaction of Lyn with all of
      these molecules except SHP-1. Cells containing the dominant-negative Lyn
      displayed altered intracellular phosphorylation patterns, including mitogen
      actiated protein kinase, but not erythropoietin receptor, Janus-activated kinase
      (JAK) 2, or STAT5. As a consequence, erythropoietin-initiated differentiation and
      basal proliferation were severely impaired. Y397F Lyn reduced the protein levels
      of erythroid transcription factors erythroid Kruppel-like factor and GATA-1 up to
      90%, which accounts for the inability of J2E cells expressing Y397F Lyn to
      synthesize hemoglobin. Although Lyn was shown to bind several sites on the
      cytoplasmic domain of the erythropoietin receptor, it was not activated when a
      receptor mutated at the JAK2 binding site was ectopically expressed in J2E cells
      indicating that JAK2 is the primary kinase in erythropoietin signaling and that
      Lyn is a secondary kinase. In normal erythroid progenitors, erythropoietin
      enhanced phosphorylation of Lyn; moreover, exogenous Lyn increased colony forming
      unit-erythroid, but not burst forming uniterythroid, colonies from normal
      progenitors, demonstrating a stage-specific effect of the kinase. Significantly,
      altering Lyn activity in J2E cells had a profound effect on the development of
      erythroleukemias in vivo: the mortality rate was markedly reduced and latent
      period extended when either wild-type Lyn or Y397F Lyn was introduced into these
      cells. Taken together, these data show that Lyn plays an important role in
      intracellular signaling in nontransformed and leukemic erythroid cells.

PMID- 11289115
TI  - Induction of the mitochondrial permeability transition mediates the killing of
      HeLa cells by staurosporine.
AB  - The role of the mitochondrial permeability transition (MPT) in the killing of
      HeLa cells by staurosporine (STR) was assessed with the use of bongkrekic acid
      (BK), an inhibitor of the MPT. BK prevented cell killing as well as biochemical
      manifestations of the MPT: (a) the loss of the mitochondrial membrane potential
      (deltapsim); (b) the release of cytochrome c from the intramembranous space to
      the cytosol; and (c) the release of malate dehydrogenase from the mitochondrial
      matrix. Stable transfectants that overexpressed Akt were also resistant to cell
      killing and did not develop an MPT. STR inhibited the phosphorylation of Bad,
      whereas Bad phosphorylation was preserved in cells that overexpress Akt. In wild
      type HeLa cells treated with STR, the content of Bax in the cytosol decreased as
      that in the mitochondria increased, a result that was again prevented by
      overexpression of Akt. Bid accumulation in the mitochondria with STR was not
      affected by overexpression of Akt. The pan-caspase inhibitor Z-Val-Ala-Val
      Asp(OMe) fluoromethylketone prevented cell killing bu not induction of the MPT.
      The data document the central role of the MPT in the killing of HeLa cells by
      STR. The data are consistent with the hypothesis that induction of the MPT is a
      consequence of the movement of Bax to the mitochondria. Phosphorylation of Bad
      prevents Bax translocation. Caspases participate in the events related to cell
      killing that occur subsequent to induction of the MPT.

PMID- 11289116
TI  - Mechanism of specific nuclear transport of adriamycin: the mode of nuclear
      translocation of adriamycin-proteasome complex.
AB  - Adriamycin (ADM), an anthracycline anticancer agent, is selectively stored in the
      nuclei of a variety of proliferating cells, but the precise mechanism of specific
      nuclear transport of ADM is not well known. Recently, we demonstrated that ADM
      shows high binding affinity to the cytoplasmic proteasomes of L1210 mouse
      leukemia cells and that taken up ADM by the cells selectively binds to
      proteasomes. Nuclear targeting of proteasome in proliferating cells may be
      mediated by the nuclear localization signals that are found in several of the
      alpha-type subunits of the 20S proteasome. To confirm nuclear transport of the
      ADM-proteasome complex, we synthesized a photoactive ADM analogue, N-(p
      azidohenzoyl)-ADM, and generated a photoaffinity-labeled proteasome complex. The
      26S proteasome purified from the cytosol of L1210 cells had a high affinity to N
      (p-azidobenzoyl)-ADM. SDS-PAGE analysis of the photoaffinity-labeled proteasome
      showed that low molecular weight bands (approximately 21-31 kDa) of 20S
      proteasome had the highest photoaffinity. The photoaffinity-labeled proteasome
      was distributed in the cytoplasm and nuclei of digitonin-permeabilized L1210 and
      B-16 mouse melanoma cells in the presence of the cytosolic fraction and ATP. The
      rate of nuclear translocation of the proteasome was low in the absence of ATP.
      These results suggest that the proteasome is a specific translocator of ADM from
      the cytoplasm to the nucleus and that 20S proteasome components are the dominant
      ADM-binding sites. The nuclear transport of ADM-proteasome complex is regulated
      by an ATP-dependent nuclear pore-mediated mechanism.

PMID- 11289117
TI  - Modulation of biomarkers by chemopreventive agents in smoke-exposed rats.
AB  - Chemoprevention opens new perspectives in the prevention of cancer and other
      chronic degenerative diseases associated with tobacco smoking, exploitable in
      current smokers and, even more, in exsmokers and passive smokers. Evaluation of
      biomarkers in animal models is an essential step for the preclinical assessment
      of efficacy and safety of potential chemopreventive agents. Groups of Sprague
      Dawley rats were exposed whole body to a mixture of mainstream and sidestream
      cigarette smoke for 28 consecutive days. Five chemopreventive agents were given
      either with drinking water (N-acetyl-L-cysteine, 1 g/kg body weight/day) or with
      the diet (1,2-dithiole-3-thione, 400 mg; Oltipraz, 400 mg; phenethyl
      isothiocyanate, 500 mg; and 5,6-benzoflavone, 500 mg/kg diet). The monitored
      biomarkers included: DNA adducts in bronchoalveolar lavage cells, tracheal
      epithelium, lung and heart; oxidative damage to pulmonary DNA; hemoglobin adducts
      of 4-aminobiphenyl and benzo(a)pyrene-7,8-diol-9,10-epoxide; micronucleated and
      polynucleated alveolar macrophages and micronucleated polychromatic erythrocytes
      in bone marrow. Exposure of rats to smoke resulted in dramatic alterations of all
      investigated parameters. N-Acetyl-L-cysteine, phenylethyl isothiocyanate, and 5,6
      benzoflavone exerted a significant protective effect on all alterations. 1,2
      Dithiole-3-thione was a less effective inhibitor and exhibited both a systemic
      toxicity and genotoxicity in alveolar macrophages, whereas its substituted
      analogue Oltipraz showed limited protective effects in this model. Interestingly,
      combination of N-acetyl-L-cysteine with Oltipraz was the most potent treatment,
      resulting in an additive or more than additive inhibition of smoke-related DNA
      adducts in the lung and hemoglobin adducts. These results provide evidence for
      the differential ability of test agents to modulate smoke-related biomarkers in
      the respiratory tract and other body compartments and highlight the potential
      advantages in combining chemopreventive agents working with distinctive
      mechanisms.

PMID- 11289118
TI  - Association between DNA repair-deficiency and high level of p53 mutations in
      melanoma of Xeroderma pigmentosum.
AB  - Xeroderma pigmentosum (XP) is an inheritable disease characterized by sun
      sensitivity and a high frequency of skin cancers including melanoma. We have
      analyzed two different groups of XP: the XP complementation group C (XP-C),
      deficient in global nucleotide excision repair but proficient in transcription
      coupled repair and associated with a very early onset of skin cancers; and the XP
      variant (XPV), deficient in the bypass of DNA photoproducts. To get new insights
      into the biology of melanoma in XP patients, we studied 20 melanomas from four XP
      C and two XPV patients in terms of pathology, immunohistochemistry of p53,
      mutations in exons 4-9 of the p53 gene, and polymorphisms of the p53 gene at
      codon 72. All statistical tests were two-sided. The majority of the XP melanomas
      were of the lentigo maligna melanoma (LMM) type, as found in the elderly. p53
      point mutations were found in 60% of XP-C melanomas and in only 10% of XPV
      melanomas, this latter frequency being similar to what has been reported in the
      general population. Mutations show the specific UV-signature because the majority
      were CC to tandem and C to T transitions located at the bipyrimidine sites known
      to be hotspots of UV-induced DNA lesions. All DNA lesions giving rise to
      mutations in XP-C melanomas were located on the nontranscribed strand of the p53
      gene, demonstrating that these patients' cells were able to carry out
      preferential repair in vivo. The LMMs found in XP-C are associated with an
      accumulation of unrepaired DNA lesions and may represent a good model for the LMM
      induction in the elderly.

PMID- 11289119
TI  - Dimethylbenzanthracene carcinogenesis in Gadd45a-null mice is associated with
      decreased DNA repair and increased mutation frequency.
AB  - Mice lacking the Gadd45a gene are susceptible to ionizing radiation-induced
      tumors. Increased levels of Gadd45a transcript and protein are seen after
      treatment of cells with ionizing radiation as well as many other agents and
      treatments that damage DNA. Because cells deficient in Gadd45a were shown to have
      a partial defect in the global genomic repair component of the nucleotide
      excision repair pathway of UV-induced photoproducts, dimethylbenzanthracene
      (DMBA) carcinogenesis was investigated because this agent produces bulky adducts
      in DNA that are also repaired by nucleotide excision repair. Wild-type mice and
      mice deficient for Gadd45a were injected with a single i.p. dose of DMBA at 10-14
      days of age. The latency for spontaneous deaths was slightly decreased for
      Gadd45a-null mice compared with wild-type mice. At 17 months, all surviving
      animals were killed, and similar percentages of each genotype were found to have
      tumors. However, nearly twice as many Gadd45a-null than wild-type mice had
      multiple tumors, and three times as many had multiple malignant tumors. The
      predominant tumor types in wild-type mice were lymphoma and tumors of the
      intestines and liver. In Gadd45a-null mice, there was a dramatic increase in
      female ovarian tumors, male hepatocellular tumors, and in vascular tumors in both
      sexes. In wild-type mice, this dose of DMBA induced a >5-fold increase in Gadd45a
      transcript in the spleen and ovary, whereas the increase in liver was >20-fold.
      Nucleotide excision repair, which repairs both UV- and DMBA-induced DNA lesions,
      was substantially reduced in Gadd45a-null lymphoblasts. Mutation frequency after
      DMBA treatment was threefold higher in Gadd45a-null liver compared with wild-type
      liver. Therefore, lack of basal and DMBA-induced Gadd45a may result in enhanced
      tumorigenesis because of decreased DNA repair and increased mutation frequency.
      Genomic instability, decreased cell cycle checkpoints, and partial loss of normal
      growth control in cells from Gadd45a-null mice may also contribute to this
      process.

PMID- 11289120
TI  - Identification of gene expression patterns in superficial and invasive human
      bladder cancer.
AB  - Multiple transcriptional events take place when normal urothelium is transformed
      into tumor tissue. These can now be monitored simultaneously by the use of
      oligonucleotide arrays, and expression patterns of superficial and invasive
      tumors can be established. Single-cell suspensions were prepared from bladder
      biopsies (36 normal, 29 tumor). Pools of cells were made from normal urothelium
      and from pTa grade I and II and pT2 grade III and IV bladder tumors. From these
      suspensions, and from 10 single-tumor biopsies, labeled cRNA was hybridized to
      oligonucleotide arrays carrying probes for 6500 genes. The obtained expression
      data were sorted according to a weighting scheme and were subjected to
      hierarchical cluster analysis of tissues and genes. Northern blotting was used to
      verify the array data, and immunohistology was used to correlate between RNA and
      protein levels. Hierarchical clustering of samples correctly identified the stage
      using both 4076 genes and a subset of 400 genes covarying with the stages and
      grades of tumors. Hierarchical clustering of gene expression levels identified
      several stage-characteristic, functionally related clusters, encoding proteins
      that were related to cell proliferation, oncogenes and growth factors, cell
      adhesion, immunology, transcription, proteinases, and ribosomes. Northern
      blotting correlated well with array data. Immunohistology showed a good
      concordance between transcript level and protein staining. The study indicates
      that gene expression patterns may be identified in bladder cancer by combining
      oligonucleotide arrays and cluster analysis. These patterns give new biological
      insight and may form a basis for the construction of molecular classifiers and
      for developing new therapy for bladder cancer.

PMID- 11289121
TI  - A risk-stratification model of non-small cell lung cancers using cyclin E, Ki-67,
      and ras p21: different roles of G1 cyclins in cell proliferation and prognosis.
AB  - A large number of biological factors that seem to have important prognostic
      significance have been identified in non-small cell lung cancers (NSCLCs). In the
      present study, we have characterized expression of cyclin D1 and cyclin E in a
      cohort of 217 resected NSCLCs from a single institution by immunohistochemistry
      to analyze their expression in relation to the growth fraction determined by Ki
      67 and to prognosis, and then we have constructed a risk-stratification model of
      cancer death by multiple biological factors in p-stage I NSCLCs. The cyclin E
      labeling index (LI) was significantly associated with the Ki-67 LI (r = 0.45; P <
      0.001). Tumors having high-level cyclin E expression (cyclin E LI > or =30%)
      showed a significantly higher Ki-67 LI than tumors having low-level cyclin E
      expression (cyclin E LI <30%; P < 0.001), whereas positive or negative cyclin D1
      expression was not associated with the Ki-67 LI (P = 0.1). Cyclin E expression
      was a significant and independent unfavorable prognostic factor (hazards ratio =
      2.09; P = 0.03), as reported previously (Clin. Cancer Res., 6: 11-16, 2000),
      whereas cyclin D1 expression was not. These findings indicate different roles of
      cyclin D1 and cyclin E in cell proliferation and in the prognosis of NSCLCs.
      Furthermore, we stratified this cohort of p-stage I NSCLCs into different
      survival groups by using biological factors, including cyclin E, Ki-67, and ras
      p21, which previously we have found to be independent prognostic factors among 10
      factors studied in p-stage I NSCLCs. Four groups of patients with markedly
      different survivals were identified with 5-year survival rates that ranged from
      96% for patients with no factors altered to 41% for patients with all three
      factors altered (P < 0.001). This combination of biological factors was a
      significant and independent prognostic factor (hazards ratio = 7.94; P = 0.001).

PMID- 11289122
TI  - Influence of TP53 gene alterations and c-erbB-2 expression on the response to
      treatment with doxorubicin in locally advanced breast cancer.
AB  - TP53 status [mutations, immunostaining, and loss of heterozygosity (LOH)],
      expression of c-erbB-2, bcl-2, and histological grading were correlated to the
      response to doxorubicin monotherapy (14 mg/m2) administered weekly to 90 patients
      with locally advanced breast cancer. Mutations in the TP53 gene, in particular
      those affecting or disrupting the loop domains L2 or L3 of the p53 protein, were
      associated with lack of response to chemotherapy (P = 0.063 for all mutations and
      P = 0.008 for mutations affecting L2/L3, respectively). Similarly, expression of
      c-erbB-2 (P = 0.041), a high histological grade (P = 0.023), and lack of
      expression of bcl-2 (P = 0.018) all predicted chemoresistance. No statistically
      significant association between either p53 immunostaining or TP53 LOH and
      response to therapy was recorded, despite the finding that both were associated
      with TP53 mutation status (p53 immunostaining, P < 0.001; LOH, P = 0.021). Lack
      of immunostaining for p53 despite mutation of the TP53 gene was particularly seen
      in tumors harboring nonsense mutations or deletions/splices (7 of 10 negative for
      staining compared with 4 of 16 with missense mutations). TP53 mutations
      (total/affecting L2/L3 domains) were associated with expression of c-erbB-2 (P <
      0.001 for both), high histological grade (P = 0.001 and P = 0.025), and bcl-2
      negativity (P = 0.003 and P = 0.002). TP53 mutations, histological grade, and
      expression of bcl-2 (but not LOH or c-erbB-2 expression) all predicted for
      relapse-free as well as breast cancer-specific survival in univariate analysis
      (Ps between <0.0001 and 0.0155), but only tumor grade was found to be predictive
      in multivariate analysis (P = 0.01 and P = 0.0007, respectively). Our data are
      consistent with the hypothesis that certain TP53 mutations predict for resistance
      to doxorubicin in breast cancer patients. However, the observation that the
      majority of patients with TP53 mutations affecting or disrupting the L2/L3
      domains with LOH in addition (n = 12) obtained a partial response (n = 4) or
      stabilization of disease (n = 5) during chemotherapy suggests redundant
      mechanisms to compensate for loss of p53 function. Our findings are consistent
      with the hypothesis that other defects may act in concert with loss of p53
      function, causing resistance to doxorubicin in breast cancers.

PMID- 11289123
TI  - Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts
      therapy outcome for primary rectal carcinoma.
AB  - Contrast enhanced dynamic studies of malignant tumors performed by computed
      tomography or magnetic resonance imaging (MRI) are increasingly applied to
      characterize tumor microcirculation for the prediction of therapy outcome. The
      aim of our study was to correlate perfusion index (PI) values determined in
      primary rectal carcinoma before chemoradiation with therapy outcome. In 17
      patients with clinically staged T3 primary rectal carcinoma, dynamic MRI was
      performed before the onset of therapy using an ultrafast T1-mapping sequence. On
      the basis of the acquired data sets, PI values were calculated on a pixel-by
      pixel basis. To characterize the heterogeneity of tumor microcirculation,
      relative cumulative frequency histograms of PI values within the tumors were
      computed. Subsequent resection of the tumors allowed correlating PI with
      histopathological classification. In 12 of 17 patients, T-downstaging as a
      response to therapy was found, whereas in the remaining 5 patients no therapy
      response was observed after chemoradiation. A statistically significant
      difference between both groups was found for the mean PI (P < 0.001; 8.5+/-1.7
      ml/min/100 g versus 11.4+/-0.7 ml/min/100 g). Analyzing the cumulative frequency
      histograms for both groups revealed an optimal discrimination for a P1 value of
      12.6 ml/min/100 g. The fraction of pixels in the tumor with PI values larger than
      12.6 ml/min/100 g was significantly different (P < 0.001) between therapy
      responding (3+/-3.6%) and therapy-nonresponding tumors (21+/-4.3%). The results
      indicate either a reduced supply of nutrients as well as chemotherapeutic agents
      attributable to increased shunt flow or highly aggressive tumor cell clusters
      characterized by increased angiogenic activity. Noninvasive PI measurements by
      dynamic MRI in rectal carcinoma before therapy seem to be of predictive value for
      therapy outcome in patients scheduled for preoperative chemoradiation.

PMID- 11289124
TI  - Molecular quantification of response to therapy and remission status in TEL-AML1
      positive childhood ALL by real-time reverse transcription polymerase chain
      reaction.
AB  - Although TEL-AML1 positivity [translocation t(12;21)(p13;q22)], detected in 20
      25% of initial childhood acute lymphoblastic leukemia (ALL), has been associated
      with an excellent prognosis, its positive predictive value is insufficient for
      appropriate treatment stratification considering reported prevalence in relapsed
      ALL (3-28%). Molecular quantification of response to therapy by PCR-based methods
      has been shown to improve risk assessment. Here, we report on the sensitive
      quantification of leukemia-specific TEL-AML1 fusion transcript levels normalized
      to beta-actin expression (sensitivity threshholds, 10(-5)) by a novel real-time
      reverse transcription-PCR (RQ-RT-PCR) based on fluorescent TaqMan technique
      providing early and rapid evidence on the treatment efficacy of children with
      initial or relapsed TEL-AML1+ ALL enrolled in frontline or relapse trials of the
      Berlin-Frankfurt-Munster (BFM)-Study Group. In initial ALL, TEL-AML1/beta-actin
      decrease was > or =10(5)-fold in 50% of patients after induction therapy (day 33)
      and stayed TEL-AML1-negative throughout therapy, which suggested high sensitivity
      of leukemic cells to antineoplastic therapy. The remaining patients were still
      TEL-AML1+ before reintensification (ratios, 0.7 x 10(-2):10(-4)). In relapsed
      ALL, TEL-AML1/beta-actin decrease was generally less pronounced at corresponding
      time points, and conversion to TEL-AML1 negativity was observed in 40% of
      patients. Most notably, subsequent relapses occurred only among molecular poor
      responders, whereas all early responders remain in their second complete
      remission. In conclusion, real-time quantification of TEL-AML1/beta-actin
      kinetics distinguishes distinct molecular response groups, and provides
      indications capable of directing therapeutic interventions for patients with TEL
      AML1+ ALL. Before considering modification of therapy, results should be
      interpreted cautiously taking into account the long duration of remission
      associated with TEL-AML1+ ALL.

PMID- 11289125
TI  - Detection of blood-borne cells in colorectal cancer patients by nested reverse
      transcription-polymerase chain reaction for carcinoembryonic antigen messenger
      RNA: longitudinal analyses and demonstration of its potential importance as an
      adjunct to multiple serum markers.
AB  - The use of reverse transcription-PCR (RT-PCR) to analyze cells in the blood of
      cancer patients for the detection of mRNA expressed in tumor cells has
      implications for both the prognosis and the monitoring of cancer patients for the
      efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA)
      is expressed on approximately 95% of colorectal, gastric, and pancreatic tumors,
      and on the majority of breast, non-small cell lung, and head and neck carcinomas.
      CEA shed in serum is useful as a marker in only approximately 50% of colorectal
      cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been
      used previously to detect CEA mRNA in cells in the blood and lymph nodes of
      cancer patients. Under the assay conditions validated in the studies reported
      here, 34 of 51 (67%) patients with different stages of colorectal cancer had
      blood cells that were positive by RT-PCR for CEA mRNA, whereas none of 18
      patients with colonic polyps were positive; 2 of 60 apparently healthy
      individuals (who were age and sex matched with the carcinoma patients and were
      part of a colon cancer screening program as controls) were marginally positive.
      The results of CEA PCR in the blood of the carcinoma patients and the other
      groups showed strong statistical correlation with the disease (P2 < 0.0001).
      Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in
      blood cells of colorectal carcinoma patients by RT-PCR. For all stages of
      disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51
      (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B
      and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23
      (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and
      CA72-4) for colorectal cancer in combination with serum CEA scored two additional
      patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term
      longitudinal studies conducted before and after surgery identified some patients
      with CEA mRNA in blood cells that were negative for all serum markers, who
      eventually developed clinical metastatic disease. The studies reported here are
      the first to correlate RT-PCR results for CEA mRNA in blood cells with one or
      more serum markers for patients with different stages of colorectal cancer, and
      are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in
      blood cells of cancer patients. Larger cohorts will be required in future studies
      to define the impact, if any, of this technology on prognosis and/or disease
      monitoring.

PMID- 11289126
TI  - Vascular endothelial growth factor and basic fibroblast growth factor urine
      levels as predictors of outcome in hormone-refractory prostate cancer patients: a
      cancer and leukemia group B study.
AB  - Better prognostic markers are needed for hormone-refractory prostate cancer
      (HRPC) patients. No single biochemical or clinical parameter can reliably predict
      patient response to therapy or rapidity of disease progression. Peptide factors
      involved in major cancer growth pathways, such as tumor angiogenesis, are
      attractive candidates as markers of low- and high-risk HRPC patients. We analyzed
      prospectively collected urine specimens from 100 of 390 HRPC patients undergoing
      therapy with the growth factor antagonist suramin as part of CALGB 9480. Levels
      of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) were assessed from day 1 of therapy (D1) and day 29 (D29) urine samples
      from this subset of 100 randomly selected patients. Growth factor levels were
      determined by standardized ELISA microtiter plate assays from a commercial (bFGF)
      or proprietary (VEGF) source. Pretreatment urine VEGF levels were predictive of
      survival. In univariate analysis, patients whose baseline urine VEGF level was <
      or =28 pg/ml (the median level) had an average survival of 17 months; those with
      baseline VEGF >28 pg/ml had a significantly shorter survival of 10 months (P =
      0.024). This difference corresponded to a 60% increased risk of dying for the
      higher urine VEGF patients (hazard ratio, 1.62; P = 0.03) and remained
      significant in multivariate analysis (hazard ratio, 1.72, P = 0.02). No
      significant correlations between urine bFGF level or change in bFGF levels and
      survival were found. These results support the notion that certain peptide growth
      factor-mediated, mitogenic pathways are important in HRPC and that their levels
      can predict outcome.

PMID- 11289127
TI  - Decreased expression of estrogen receptor beta protein in proliferative
      preinvasive mammary tumors.
AB  - To understand the significance of estrogen receptor beta (ERbeta) in mammary
      carcinogenesis, we evaluated the expression of ERbeta in preinvasive mammary
      tumors. The percentage of ERbeta-positive epithelial or tumoral cells was assayed
      by quantitative immunohistochemistry using an image analyzer in 130 lesions of
      varying histological risk from 118 patients [71 with benign breast disease (BBD)
      and 59 with carcinoma in situ (CIS)] and compared with 118 adjacent
      histologically normal glands. Five groups of lesions with an increasing risk of
      invasive cancer, from BBD without hyperplasia to high-grade CIS, were studied.
      Results were compared with ERalpha and Ki67 immunostaining. The percentage of
      ERbeta-positive cells was high (median, 85%) in "normal" mammary glands and in
      nonproliferative BBD and decreased significantly (P < 0.0001) in proliferative
      BBD without atypia and in CIS, contrasting with an inverse progression for the
      ERalpha level. In normal mammary glands, the ERbeta level did not vary according
      to the nature of the lesion at the periphery and was significantly higher (P <
      0.007) than in adjacent preinvasive lesions, except in nonproliferative BBD. The
      ERbeta level decreased in proliferative BBD, anticipating the ERalpha increase,
      which was significant in BBD with atypia. In high-grade ductal carcinoma in situ,
      both ER levels were low. The ratio between ERbeta and ERalpha was high in normal
      glands, and decreased significantly in proliferative lesions. ERbeta staining was
      inversely correlated with Ki67 (r = -0.333; P < 0.001), more particularly in high
      grade ductal carcinoma in situ (r = -0.57; P < 0.02). The marked and early
      decreased level of ERbeta protein associated with other criteria of cell
      proliferation suggests a protective effect of ERbeta against the mitogenic
      activity of estrogens in mammary premalignant lesions. Knowledge of the ERbeta
      and ERalpha content in each preinvasive lesion should help to rationalize
      antiestrogen preventive therapy adapted to each individual patient.

PMID- 11289128
TI  - Transplacental chemical exposure and risk of infant leukemia with MLL gene
      fusion.
AB  - Infant acute leukemia (IAL) frequently involves breakage and recombination of the
      MLL gene with one of several potential partner genes. These gene fusions arise in
      utero and are similar to those found in leukemias secondary to chemotherapy with
      inhibitors of topoisomerase II (topo-II). This has led to the hypothesis that in
      utero exposures to chemicals may cause IAL via an effect on topo-II. We report a
      pilot case-control study of IAL across different countries and ethnic groups.
      Cases (n = 136) were population-based in most centers. Controls (n = 266) were
      selected from inpatients and outpatients at hospitals serving the same
      populations. MLL rearrangement status was derived by Southern blot analysis, and
      maternal exposure data were obtained by interviews using a structured
      questionnaire. Apart from the use of cigarettes and alcohol, very few mothers
      reported exposure to known topo-II inhibitors. Significant case-control
      differences were apparent for ingestion of several groups of drugs, including
      herbal medicines and drugs classified as "DNA-damaging," and for exposure to
      pesticides with the last two being largely attributable, respectively, to one
      nonsteroidal anti-inflammatory drug, dipyrone, and mosquitocidals (including
      Baygon). Elevated odds ratios were observed for MLL+ve (but not MLL-ve) leukemias
      (2.31 for DNA-damaging drugs, P = 0.03; 5.84 for dipyrone, P = 0.001; and 9.68
      for mosquitocidals, P = 0.003). Although it is unclear at present whether these
      particular exposures operate via an effect on topo-II, the data suggest that
      specific chemical exposures of the fetus during pregnancy may cause MLL gene
      fusions. Given the widespread use of dipyrone, Baygon, and other carbamate-based
      insecticides in certain settings, confirmation of these apparent associations is
      urgently required.

PMID- 11289129
TI  - Reciprocal expression of ERalpha and ERbeta is associated with estrogen-mediated
      modulation of intestinal tumorigenesis.
AB  - Menopausal hormone replacement therapy has been widely used to alleviate the
      symptoms of menopause and to decrease the detrimental effects of ovarian hormone
      loss on bone density and cardiovascular health. Multiple studies of colorectal
      cancer epidemiology also support a role for hormone replacement therapy in
      prevention of colorectal cancer. We studied the effect of ovariectomy and
      estrogen replacement on tumor formation in C57BL/6J-Min/+ (Min/+) mice, animals
      that bear a germline mutation in murine Apc. These mice develop multiple
      intestinal tumors that show loss of wild-type Apc protein. After ovariectomy,
      intestinal adenomas in Min/+ mice increased by 77% (P = 0.0004). Ovariectomized
      Min/+ mice that were treated with a replacement dose of 17beta-estradiol had the
      same number of tumors as Min/+ mice that were neither castrated nor treated with
      estrogen replacement (P = 0.85). Examination of estrogen receptor (ER) levels in
      intestinal tissue by immunoblot showed changes in relative expression levels of
      ERalpha and ERbeta, with highest ERalpha and lowest ERbeta expression in the
      normal-appearing intestine of Min/+ mice, and lowest ERalpha and highest ERbeta
      expression in the enterocytes of animals that received 17beta-estradiol. These
      results suggest that endogenous estrogens protect against Apc-associated tumor
      formation and that tumor prevention by 17beta-estradiol is associated with an
      increase in ERbeta and a decrease in ERalpha expression in the target tissue.

PMID- 11289131
TI  - Cell surface-directed interaction of anthracyclines leads to cytotoxicity and
      nuclear factor kappaB activation but not apoptosis signaling.
AB  - Anthracyclines are, above all, DNA intercalators, which induce genetic damage
      leading to cell death. However, increasing evidence firmly suggests that the
      underlying mechanism for anthracycline cytotoxicity is the induction of apoptosis
      through intracellular-mediated signaling pathways. Whether drug/DNA interaction
      is necessary for such apoptosis signaling is unknown. We investigated the
      cellular effects of the anthracyclines daunorubicin (DNR) and doxorubicin (DOX)
      using the myeloid leukemia cell line U937. By comparing free drug against agarose
      bead-immobilized drug iDNR and iDOX (which cannot accumulate within the cell), we
      observed that whereas both free and immobilized anthracyclines were cytotoxic,
      only the former induced apoptosis; the latter induced necrosis. Indeed, we did
      not observe ceramide generation, neutral sphingomyelinase activation, poly (ADP
      ribose) polymerase cleavage, or other apoptotic events with iDNR or iDOX.
      However, both free and immobilized drug were similarly capable of triggering
      nuclear factor kappaB activation. These observations demonstrate that whereas
      activation of certain cellular signaling pathways can be achieved solely through
      membrane interaction, apoptosis signaling requires anthracycline internalization.
      These results also show that the initiation of cell survival pathways
      (illustrated by nuclear factor kappaB activation) is independent of intracellular
      drug/target interaction.

PMID- 11289130
TI  - Peptide transport by the multidrug resistance protein MRP1.
AB  - Small hydrophobic peptides were studied as possible substrates of the multidrug
      resistance protein (MRP)-1 (ABCC1) transmembrane transporter molecule. As
      observed earlier for P-glycoprotein- (Pgp; ABCB1) overexpressing cells, MRP1
      overexpressing cells, including cells stably transfected with the MRP1 cDNA,
      showed distinct resistance to the cytotoxic peptide N-acetyl-Leu-Leu-norleucinal
      (ALLN). Resistance to this peptide and another toxic peptide derivative, which is
      based on a Thr-His-Thr-Nle-Glu-Gly backbone conjugated to butyl and benzyl groups
      (4A6), could be reversed by MRP1 inhibitors. The reduced toxicity of 4A6 in MRP1
      overexpressing cells was found to be associated with lower accumulation of a
      fluorescein-labeled derivative of this peptide. Glutathione (GSH) depletion had a
      clear effect on resistance to ALLN but hardly affected 4A6 resistance. In a
      limited structure-activity study using peptides that are analogous to 4A6, MRP1
      overexpressing cells were found to be resistant to these peptides as well.
      Remarkably, when selecting A2780 ovarian cancer cells for resistance to ALLN,
      even in the absence of Pgp blockers, resulting cell lines had up-regulated MRP1,
      rather than any of the other currently known multidrug resistance transporter
      molecules including Pgp, MRP2 (ABCC2), MRP3 (ABCC3), MRP5 (ABCCS), and the breast
      cancer resistance protein ABCG2. ALLN-resistant, MRP1-overexpressing cells were
      found to be cross-resistant to 4A6 and the classical multidrug resistance drugs
      doxorubicin, vincristine, and etoposide. This establishes MRP1 as a transporter
      for small hydrophobic peptides. More extensive structure-activity relationship
      studies should allow the identification of clinically useful peptide antagonists
      of MRP1.

PMID- 11289132
TI  - Adenovirus-mediated transfer of inducible caspases: a novel "death switch" gene
      therapeutic approach to prostate cancer.
AB  - In patients with localized prostate cancer, radical prostatectomy and radiation
      therapy, although effective in controlling localized disease, are often
      associated with significant side effects attributable to injury of adjacent
      tissues. Moreover, patients with metastatic disease eventually fail systemic
      hormonal or chemotherapy because of the development of progressive, refractory
      disease. In this study, we evaluated the safety and efficacy of a novel suicide
      gene therapy that could potentially spare normal tissue while bypassing molecular
      mechanisms of apoptosis resistance by using chemically inducible effector
      caspases to trigger apoptosis in prostate cancer cells. Initially, we compared
      the ability of a panel of inducible Fas signaling intermediates to kill human and
      murine prostate cancer cell lines. On the basis of the superior killing by
      downstream caspase-1 and caspase-3, replication-deficient adenoviral vectors
      expressing conditional caspase-1 (Ad-G/iCasp1) or caspase-3 (Ad-G/iCasp3),
      regulated by nontoxic, lipid-permeable, chemical inducers of dimerization (CID),
      were constructed. Upon vector transduction followed by CID administration,
      aggregation and activation of these recombinant caspases occur, leading to rapid
      apoptosis. In vitro, both human (LNCaP and PC-3) and murine (TRAMP-C2 and TRAMP
      C2G) prostate cancer cell lines were efficiently transduced and killed in a CID
      dependent fashion. In vivo, direct injection of Ad-G/iCasp1 into s.c. TRAMP-C2
      tumors caused focal but extensive apoptosis without evidence for a bystander
      effect at the maximal viral dose (i.e., 2.5 x 10(10) viral particles/25 microl)
      in host animals that also received CID compared with control animals. Treatment
      with Ad-G/iCasp1 plus CID resulted in a transient, yet significant, reduction
      both in tumor growth and volume compared with tumors treated with vector but not
      CID (P < 0.035) or vector-diluent plus CID (P < 0.022), both of which grew more
      rapidly. These results demonstrate that CID-regulated, caspase-based suicide gene
      therapy is safe and can inhibit the growth of experimental prostate cancer in
      vitro and in vivo through potent induction of apoptosis, providing a rationale
      for further development.

PMID- 11289133
TI  - Therapeutic efficacy of a soluble receptor activator of nuclear factor kappaB-IgG
      Fc fusion protein in suppressing bone resorption and hypercalcemia in a model of
      humoral hypercalcemia of malignancy.
AB  - Receptor activator of nuclear factor kappaB (RANK) is a membrane-bound tumor
      necrosis factor receptor homologue that mediates signals obligatory for
      osteoclastogenesis as well as osteoclast activation and survival in vivo. The
      present study was undertaken to evaluate the efficacy of a soluble murine RANK
      human immunoglobulin fusion protein (muRANK.Fc) as a bone resorption inhibitor in
      vitro and in vivo. The in vitro studies demonstrated the ability of muRANK.Fc to
      inhibit human parathyroid hormone-related protein (PTHrP)-induced resorption in
      fetal rat long bone cultures. Short-term administration of muRANK.Fc to normal
      growing mice resulted in a complete disappearance of osteoclasts from metaphyses
      of long bones associated with a pronounced increase in calcified trabeculae and
      bone radiodensity. In a model of humoral hypercalcemia of malignancy in which
      PTHrP secreted by s.c. xenografts of human lung cancer in nude mice induces
      extensive osteolysis and severe hypercalcemia, daily administration of muRANK.Fc
      from time of tumor implantation profoundly inhibited osteoclastic bone resorption
      and prevented hypercalcemia. muRANK.Fc had no effect on tumor production of
      PTHrP, because there was no significant difference between circulating human
      PTHrP levels in muRANK.Fc-treated and vehicle-treated tumor-bearing mice.
      Moreover, even when treatment was initiated after hypercalcemia was established,
      muRANK.Fc significantly attenuated further increases in blood ionized calcium.
      These data demonstrate the potent antiresorptive effects of muRANK.Fc in vivo as
      well as highlight the potential utility of disrupting RANK signaling as a novel
      therapeutic approach in humoral hypercalcemia of malignancy and possibly multiple
      myeloma and skeletal metastases associated with osteolysis.

PMID- 11289134
TI  - Selective sensitization of retinoblastoma protein-deficient sarcoma cells to
      doxorubicin by flavopiridol-mediated inhibition of cyclin-dependent kinase 2
      kinase activity.
AB  - We examined the effects of flavopiridol (FP), a cyclin-dependent kinase
      inhibitor, on doxorubicin (DOX)-induced cell killing in an osteosarcoma cell line
      (SaOs-2) that lacks functional retinoblastoma protein (pRb). The IC50 value for
      DOX was 7-fold lower when combined with a low dose (100 nM) FP in pRb-deficient
      SaOs-2 cells than in the absence of FP. In contrast, the IC50 value for DOX was
      not decreased in the presence of 100 nM FP in pRb-restored SaOs-2 cells.
      Consistent with this, FP enhanced DOX-induced activation of caspase-3, which
      correlates with apoptosis, in pRb-deficient cells but not in pRb-restored cells.
      Additional studies showed that FP decreased DOX-induced cell accumulation in S
      phase in retinoblastoma-restored cells but not in pRb-deficient cells. An
      increased expression of p21 and inhibition of cyclin-dependent kinase 2 kinase
      activity by FP was also observed in pRb-deficient cells but not in retinoblastoma
      restored SaOs-2 cells. We conclude that pRb plays a key role in determining
      whether FP selectively sensitizes DOX-induced cell killing in human sarcoma
      cells. Because lack of functional pRb is a common abnormality in human cancers,
      the combination of FP with DOX in tumors lacking pRb would be worthy of further
      investigation.

PMID- 11289135
TI  - The cyclin-dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12
      myristate 13-acetate-induced differentiation and CDKI expression while enhancing
      apoptosis in human myeloid leukemia cells.
AB  - Interactions between the cyclin-dependent kinase inhibitor (CDKI) flavopiridol
      (FP) and phorbol 12-myristate 13-acetate (PMA) were examined in U937 human
      leukemia cells in relation to differentiation and apoptosis. Simultaneous, but
      not sequential, exposure of U937 cells to 100 nM FP and 10 nM PMA significantly
      increased apoptosis manifested by characteristic morphological features,
      mitochondrial dysfunction, caspase activation, and poly(ADP-ribose) polymerase
      cleavage while markedly inhibiting cellular differentiation, as reflected by
      diminished plastic adherence and CD11b expression. Enhanced apoptosis in U937
      cells was associated with an early caspase-independent increase in cytochrome c
      release and accompanied by a substantial decline in leukemic cell clonogenicity.
      Moreover, PMA/FP cotreatment significantly increased apoptosis in HL-60
      promyelocytic leukemia cells and in U937 cells ectopically expressing the Bcl-2
      protein. In U937 cells, coadministration of FP blocked PMA-induced expression and
      reporter activity of the CDKI p21WAF/CIP1 and triggered caspase-mediated cleavage
      of the CDKI p27KIP1. Coexposure to FP also resulted in a more pronounced and
      sustained activation of the mitogen-activated protein kinase kinase/extracellular
      signal-regulated protein kinase cascade after PMA treatment, although disruption
      of this pathway by the mitogen-activated protein kinase kinase 1 inhibitor U0126
      did not prevent potentiation of apoptosis. FP accelerated PMA-mediated
      dephosphorylation of the retinoblastoma protein (pRb), an event followed by pRb
      cleavage culminating in the complete loss of underphosphorylated pRb
      (approximately Mr 110,000) by 24 h. Finally, gel shift analysis revealed that
      coadministration of FP with PMA for 8 h led to diminished E2F/pRb binding
      compared to the effects of PMA alone. Collectively, these findings indicate that
      FP modulates the expression/activity of multiple signaling and cell cycle
      regulatory proteins in PMA-treated leukemia cells and that such alterations are
      associated with mitochondrial damage and apoptosis rather than maturation. These
      observations also raise the possibility that combining CDKIs and differentiation
      inducing agents may represent a novel antileukemic strategy.

PMID- 11289136
TI  - Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44
      overexpressing tumor cells.
AB  - Certain tumors, including many that are found in the lung, overexpress the CD44
      cell-surface marker. CD44 is a receptor that binds to hyaluronan (HA), a
      carbohydrate consisting of beta1,3 N-acetyl glucosaminyl-beta1,4 glucuronide. We
      hypothesized that the incorporation of phosphatidylethanolamine lipid derivatives
      containing HA oligosaccharides (HA-PE) into liposomes could target drug
      containing liposomes to tumor cells that express CD44. HA-PE containing palmitoyl
      oleoyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine (HAn-PE)
      were incorporated into the lipid bilayer at various mole percentages of the total
      lipids; and the physicochemical properties (diameter, surface charge, and
      stability) of the resulting liposome preparations were characterized. HA-targeted
      liposomes (HALs) avidly bound to the CD44-high-expressing B16F10 murine melanoma
      cell line but not to the CV-1 African green monkey kidney cells, which express
      CD44 at low levels. Binding of the HALs to the B16F10 cells was rapid,
      concentration dependent, and saturated at a lipid concentration of about 250
      microM. HAL binding to B16F10 was inhibited by HA with high Mr and by an anti
      CD44 monoclonal antibody. Binding to the B16 melanoma cells occurred at a lipid
      composition that contained a > or =0.1 mol % of the HAn-PE lipid. The bound
      liposomes were internalized by a temperature-dependent process. The IC50s of
      doxorubicin (DOX) encapsulated in either HALs or nontargeted liposomes and of
      nonencapsulated DOX were compared in two protocols: continuous exposure of the
      cells to treatment for 24 h and transient exposure in which the treatment was
      applied for a 3-h period, and in which non-cell-associated drug was replaced with
      drug-free medium for the duration of the experiment. The IC50s of free DOX, DOX
      loaded nontargeted liposomes, and DOX-loaded HAL (HAL-DOX) for the transient
      exposure were 6.4 microM, > 172 microM, and 0.78 microM, respectively. For the
      continuous exposure protocol, the IC50s were 0.60 microm, 25.0 microl, and 0.14
      microm, respectively. Thus, in both protocols, delivered DOX was significantly
      more potent than the nonencapsulated DOX in cells expressing high levels of CD44,
      which suggests that HALs may be a useful targeted drug carrier to treat CD44
      expressing tumors.

PMID- 11289137
TI  - Bisphosphonate treatment inhibits the growth of prostate cancer cells.
AB  - The presence of skeletal metastases in patients suffering from cancer leads to a
      variety of clinical complications. Bisphosphonates are a class of drugs with a
      potent bone resorption inhibition activity that have found increasing utility in
      treating and managing patients with metastatic bone disease. Several clinical
      trials have demonstrated that bisphosphonates have clinical value in the
      treatment and management of skeletal metastases derived from advanced prostate
      cancer. Currently, the mechanism(s) through which bisphosphonates exert their
      activity is only beginning to be understood. We have studied the effects of
      bisphosphonate treatment on the growth of prostate cancer cell lines in vitro.
      Treatment of PC3, DU145, and LNCaP cells with pamidronate or zoledronate
      significantly reduced the growth of all three cell lines. Using flow cytometry,
      pamidronate treatment (100 microM) was shown to induce significant amounts of
      cell death in all three cell lines studied. In contrast, treatment with
      zoledronate (100 microM) did not induce cell death, instead exerting dramatic
      effects on cell proliferation, as evidenced by a major increase in cells present
      in the G0-G1 and S phase. Although both drugs reduced prostate cancer cell growth
      in the presence of serum, zoledronate was more potent under these conditions,
      disrupting growth at doses as low as 25 microM in the presence of 5% fetal bovine
      serum. These results raise the intriguing possibility that the observed clinical
      utility of bisphosphonates in managing skeletal metastases may in part derive
      from direct inhibition of prostate cancer cell growth in the bone
      microenvironment.

PMID- 11289138
TI  - Growth suppression of the hepatocellular carcinoma cell line Hepa1-6 by an
      activatable interferon regulatory factor-1 in mice.
AB  - Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis
      and few therapeutic options. The aim of the study was to evaluate the potential
      of IFN regulatory factor-1 (IRF-1) for cytokine gene therapy of HCC using an IRF
      1/human estrogen receptor fusion protein (IRF-1hER), which is reversibly
      activatable by beta-estradiol (E2). IRF-1hER stably expressing murine Hepa1-6 HCC
      cells (HepaIRF-1hER) were characterized by lowMHC 1, highCD54, and lack of MHC
      II, CD80, and CD86 expression. Activation of HepaIRF-1hER cells induced a highMHC
      I, lowMHC II, and highCD54 phenotype. Furthermore, they were characterized by IFN
      beta secretion, decreased anchorage-independent growth in a soft agar assay, and
      diminished cell growth. Tumor growth in E2-treated syngeneic C57L/J mice, but not
      in E2-untreated mice, was suppressed. These E2-treated mice were protected
      against rechallenge with HepaIRF-1hER and wild-type Hepa1-6 tumors even in the
      absence of E2, suggesting induction of tumor specific immunity. In fact,
      significant CTL activity against Hepa1-6 tumors and the endogenously expressed
      HCC-specific self antigen alpha-fetoprotein was observed. Antitumoral effects,
      however, were only partially dependent on both CD4+ and CD8+ T cells. IRF-1
      treatment of mice bearing HepaIRF-1hER tumors resulted in growth arrest of
      tumors, and a significant survival benefit was observed in comparison to E2
      untreated mice. In conclusion, our data demonstrate that IRF-1 suppresses HCC
      growth through both a direct antitumor growth effect and enhanced immune cell
      recognition of the tumor and is a promising candidate for gene therapy of HCC.

PMID- 11289139
TI  - Enhancement of tumor lysate- and peptide-pulsed dendritic cell-based vaccines by
      the addition of foreign helper protein.
AB  - We have evaluated whether the addition of a foreign helper protein, keyhole
      limpet hemocyanin (KLH), can augment the efficacy of tumor lysate-pulsed
      dendritic cells and peptide-pulsed DC immunizations in vivo. Besides being used
      as a "surrogate antigen" in approaches to measure immunological response in
      cancer patients, KLH is also an immunogenic carrier protein to elicit T-cell
      help. Using the D5 subline of B16 melanoma, we demonstrate that DCs pulsed with
      both KLH and tumor lysate mediate enhanced immune priming and rejection of
      established metastases in vivo, which is dependent on host-derived T cells.
      Interleukin 2 augments the enhancement afforded by KLH, as measured by cure rates
      and overall survival, in the absence of autoimmune depigmentation. KLH added to
      DC immunizations markedly enhances tumor-specific T cell production of IFN-gamma.
      D5 melanoma exposed to similar levels of IFN-gamma results in substantial
      expression of MHC class I molecules. DCs pulsed with KLH and mouse tyrosinase
      related protein-2 peptide results in enhanced reduction of B16 melanoma
      metastases; the effect is most pronounced in a setting where tyrosinase-related
      protein-2 peptide-pulsed DCs alone are completely ineffective. Collectively,
      these findings demonstrate that KLH addition to tumor antigen-pulsed DC
      immunizations can augment IFN-gamma production and enhance in vivo antitumor
      activity.

PMID- 11289140
TI  - Immunization with an antigen identified by cytokine tumor vaccine-assisted SEREX
      (CAS) suppressed growth of the rat 9L glioma in vivo.
AB  - We have reported previously that s.c. immunization of rats with IL-4 transduced
      9L gliosarcoma cells (9L-IL-4) induced a potent antitumor immunity against
      intracranial, parental 9L tumors. Subcutaneous implantation of 9L-IL-4 influenced
      the systemic humoral response, which was demonstrated by Th2-type isotype
      switching and the induction of cellular immune responses, which played a critical
      role in the rejection of tumors. Serological analyses of recombinant cDNA
      expression libraries (SEREX), has recently emerged as a powerful method for
      serological identification of tumor-associated antigens (TAAs) and/or tumor
      rejection antigens (TRAs). Because IL-4 is known to activate B cells and to
      promote humoral responses, and inasmuch as induction of humoral responses by
      central nervous system tumors has been reported to be minimal, we investigated
      whether the induction of a potent humoral immune response against 9L TAAs or TRAs
      in rats immunized s.c. with 9L-IL4 could be demonstrated. Screening of 5 x 10(5)
      independent clones of 9L-expression cDNA library for the presence of reactive
      antibodies in the serum from a 91-IL-4 immunized rat led to the identification of
      three different TAAs. One 9L TAA (clone 29) was demonstrated to be calcyclin, a
      member of the S-100 family of calcium-binding proteins. The second 9L TAA (clone
      37) was demonstrated to be the rat homologue of the J6B7 mouse immunomodulatory
      molecule. The third TAA (clones 158 and 171) was determined to be the rat
      homologue of the mouse Id-associated protein 1 (MIDA1), a DNA-binding, protein
      associated protein. Northern blotting demonstrated that message for calcyclin was
      overexpressed in 9L cells. Message encoding MIDA1 was highly expressed in
      parental 9L cells and thymus and, to a lesser degree, in testis, suggesting that
      MIDA1 was comparable with the cancer/testis category of TAAs. Sera obtained from
      animals bearing 9L-IL-4 were found to have a higher a frequency and titer of
      antibodies to these antigens when compared with sera obtained from rats bearing
      sham-transduced 9L (9L-neo) cells. To determine whether immunization with these
      TAAs induced antitumor immunity, animals were immunized by intradermal injection
      with expression plasmids encoding calcyclin or MIDA1. Subsequent challenge of
      rats with parental 9L resulted in significant suppression of tumor growth in
      animals immunized with MIDA1, but not with calcyclin. These results indicate that
      MIDA1 is an effective 9L TRA and will be useful for the investigation of specific
      antitumor immunity in this glioma model. Furthermore, these results suggest that
      this approach, termed "cytokine-assisted SEREX (CAS)," may serve as an effective
      strategy for identification of TRAs for in animal-glioma models of cytokine gene
      therapy, and potentially in humans undergoing cytokine gene therapy protocols as
      well.

PMID- 11289141
TI  - Single nucleotide instability without microsatellite instability in rat mammary
      carcinomas.
AB  - Mutation frequencies (MnFs) of the lacI transgene and mutation rates (MRs) of the
      endogenous hprt gene were analyzed in two mammary carcinoma cell lines that we
      established from mammary carcinomas that had been induced by 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) in female lacI-transgenic rats. Using the
      lacI transgene, corrected MnF, which is the number of independent lacI mutations
      that occurred while 102 cells expanded into 10(7) cells and which reflect the
      dynamic increase of point mutations, was measured. The corrected MnFs in the two
      mammary carcinoma cell lines (59 x 10(-6) and 72 x 10(-6) mutations) were
      significantly higher than that in the primary culture of normal mammary
      epithelium (4.7 x 10(-6)). MRs of the hprt gene in the two mammary carcinoma cell
      lines (8.2 x 10(-7) and 11 x 10(-7) mutations/hprt/cell division) were also
      higher than the same control (1.4 x 10(-7)). A:T to C:G transversion was observed
      at significantly higher frequencies in the two cell lines (6 of 24 and 6 of 25
      for lacI; 10 of 67 and 19 of 92 for hprt) than in the control (0 of 6 for lacI; 0
      of 4 for hprt). Taking advantage of the lacI transgene, high frequencies of A:T
      to C:G transversion (6 of 38 and 8 of 33, respectively) was also confirmed in the
      primary carcinomas of the two cell lines, which indicated the presence of a
      common abnormality in the cell lines and in the primary carcinomas. Both the
      established cell lines and their primary carcinomas were negative for
      microsatellite instability, which is known to be caused mainly by mismatch repair
      insufficiency and to increase point mutations, and for p53 mutations. These
      findings showed that the two cell lines, and possibly their primary carcinomas,
      had increases in the MRs of point mutations attributable to a mechanism(s)
      different from mismatch repair insufficiency, and we would suggest that such a
      state be designated as single nucleotide instability (SNI).

PMID- 11289142
TI  - The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes
      endothelial cell survival through the activation of Akt/protein kinase B.
AB  - The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor (KSHV
      GPCR) is a key molecule in the pathogenesis of Kaposi's sarcoma, playing a
      central role in the promotion of vascular endothelial growth factor (VEGF)-driven
      angiogenesis and spindle cell proliferation. We previously have shown that KSHV
      GPCR has oncogenic potential when overexpressed in fibroblasts and is responsible
      for the expression and secretion of VEGF through the regulation of different
      intracellular signaling pathways (A. Sodhi et al., Cancer Res., 60: 4873-4880,
      2000; C. Bais et al., Nature, 391: 86-89, 1998). Here, we describe that this
      constitutively active G protein-coupled receptor is able to promote cell survival
      in primary human umbilical vein endothelial cells and that this effect is
      independent of its ability to secrete VEGF because it is not prevented by the
      expression of antisense constructs for VEGF or the addition of VEGF-blocking
      antibodies. Instead we found that ectopic expression of KSHV-GPCR potently
      induces the kinase activity of Akt/protein kinase B in a dose-dependent manner
      and triggers its translocation to the plasma membrane. This signaling pathway
      requires the function of phosphatidylinositol 3'-kinase and is dependent on
      betagamma subunits released from both pertussis toxin-sensitive and -insensitive
      G proteins. Furthermore, we found that KSHV-GPCR is able to protect human
      umbilical vein endothelial cells from the apoptosis induced by serum deprivation
      and that both wortmannin and the expression of a kinase-deficient Akt K179M
      mutant are able to block this effect. Finally, we observed that the Akt K179M
      protein also inhibits the activation of nuclear factor-KB induced by KSHV-GPCR,
      suggesting that this transcription factor may represent one of the putative
      downstream targets for Akt in the survival-signaling pathway. These results
      provide further knowledge in the elucidation of the signal transduction pathways
      activated by KSHV-GPCR and support its key role in promoting the survival of
      viral-infected cells. Moreover, the present findings also emphasize the
      importance of this G protein-coupled receptor in the development of KSHV-related
      neoplasias.

PMID- 11289143
TI  - Severe combined immunodeficient cells expressing mutant hRAD54 exhibit a marked
      DNA double-strand break repair and error-prone chromosome repair defect.
AB  - DNA double-strand breaks (DSBs) can be induced by a number of endogenous and
      exogenous agents and are lethal events if left unrepaired. DNA DSBs can be
      repaired by homologous recombination (HR) and nonhomologous end joining (NHEJ).
      In mammals and higher eukaryotes, NHEJ is thought to be the primary pathway for
      repair, but the role for each pathway in DNA DSB repair has not been fully
      elucidated. To define the relative contributions of HR and NHEJ in mammalian DNA
      DSB repair, cells defective in both pathways were produced. Double-mutant cells
      were created by expressing a dominant mutant hRAD54 protein in a DNA-dependent
      protein kinase (DNA-PK)-deficient severe combined immunodeficient cell line.
      Double-mutant cells demonstrate an increase in ionizing radiation sensitivity and
      a decrease in DNA DSB repair as compared with either single mutant, whereas
      single-mutant hRAD54 cells exhibit a wild-type phenotype. Unexpectedly, DNA-PK
      null cells were more resistant to mitomycin-C damage than were wild-type cells.
      Chromosome aberration analysis reveals numerous incomplete chromatid exchange
      aberrations in the majority of the double-mutant cells after ionizing radiation
      exposure. Our findings confirm a role for HR in DSB repair in higher eukaryotes,
      yet indicate that its role is not evident unless the primary repair pathway,
      NHEJ, is nonfunctional. Mitomycin-C resistance in DNA-PK-null cells compared with
      wild-type cells suggests that the HR pathway may be more efficient in cross-link
      repair in the absence of NHEJ. Lastly, the incorrectly repaired chromatid damage
      observed in double-mutant cells may result from failed recombination or another
      error-prone repair process that is apparent in the absence of the two primary
      repair pathways.

PMID- 11289144
TI  - Antiproliferative and antiapoptotic effects of crel may occur within the same
      cells via the up-regulation of manganese superoxide dismutase.
AB  - Rel/nuclear factor kappaB transcription factors were shown to have either pro- or
      antiapoptotic as well as pro- or antiproliferative functions, and it is often
      assumed that the outcome of their activation depends on the cell type or cellular
      context. Inconsistent with this assumption, we show here that cRel is able in one
      cell type to inhibit proliferation, protect against apoptosis induced by tumor
      necrosis factor alpha (TNF-alpha) + cycloheximide (CHX), and increase the basal
      rate of apoptosis. Both the effects of proliferation inhibition and protection
      against TNF-alpha + CHX-induced apoptosis are massive and occur in the same
      cells. Using reverse transcription-PCR, Western blot and immunofluorescence, and
      transactivation assays, we found that the manganese superoxide dismutase (MnSOD),
      an enzyme that converts O2*- in H2O2, is up-regulated by cRel through a kappaB
      site in intron 2. Inhibition of MnSOD induction by antisense oligonucleotides and
      overexpression of MnSOD respectively reverts and mimics both the
      antiproliferative and antiapoptotic effects of cRel, suggesting that they both
      occur via the induction of this gene. On one hand, MnSOD could improve the
      efficiency of cRel-overexpressing cells in eliminating toxic O2*- produced on TNF
      alpha treatment, explaining why they escape TNF-alpha-induced apoptosis. On the
      other hand, cRel-overexpressing cells should accumulate H2O2. We present evidence
      linking this H2O2 accumulation to the proliferation arrest induced by cRel.
      Therefore, different effects on proliferation and apoptosis could arise from the
      induction of MnSOD and thus coexist in cRel-overexpressing cells.

PMID- 11289145
TI  - t(11;14)(q23;q24) generates an MLL-human gephyrin fusion gene along with a de
      facto truncated MLL in acute monoblastic leukemia.
AB  - More than 20 different partner genes with MLL have been cloned from leukemia
      cells with translocations involving chromosome 11 band q23 (11q23). All reported
      partner genes fused in-frame to MLL and the fusion cDNA encode chimeric MLL
      proteins with a significant portion derived from the partner genes. We analyzed
      one patient with de novo acute monoblastic leukemia with t(11;14)(q23;q24) and
      identified that a human homologue of gephyrin (human gephyrin) fused with MLL.
      Gephyrin is a rat glycine receptor-associated protein, which forms submembranous
      complexes and anchor glycine or gamma-aminobutyric acidA receptors to
      microtubules. Alternative splicing of human gephyrin gene created two different
      forms of fusion cDNA. In one form, human gephyrin gene fused in-frame to MLL exon
      9, and the chimeric product had COOH terminus of human gephyrin protein,
      including the tubulin binding site. In the other, the reading frame terminated
      shortly after the fusion point. As a result, only seven amino acids with no known
      function were attached to the NH2 terminus of MLL protein. The functional
      significance of this de facto truncated MLL gene product is not clear.

PMID- 11289146
TI  - K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of
      the protein kinase B1.
AB  - Cyclooxygenase (COX) 2 expression is regulated via the Ras signaling pathway, and
      induction of mutated Ras rapidly increases COX-2 levels in intestinal epithelial
      cells. Protein kinase B (Akt/PKB) is an important effector of Ras signaling and a
      critical component of Ras-mediated transformation. Here we investigate the role
      of Akt/PKB in K-Ras-mediated induction of COX-2. Rat intestinal epithelial cells
      (IEC-6) were transfected with an inducible K-RasVal12 cDNA (IEC-iK-Ras cells).
      Addition of 5 mM isopropyl-1-thio-beta-D-galactopyranoside induced the expression
      of K-RasVal12, followed by increased activity of extracellular signal-regulated
      kinase and Akt/PKB. COX-2 levels were dramatically increased after induction of K
      RasVal12. Inhibition of MAPK/ERK kinase activity by PD 98059 completely blocked
      the K-Ras-mediated induction of COX-2, whereas inhibition of PI3K/Akt/PKB
      activity with LY 294002 or by expressing a dominant negative Akt (Akt-K179M)
      partially blocked the induction of COX-2 by K-Ras. Transient transfection of
      cells with phosphatidylinositol 3-kinase and Akt expression vectors revealed that
      PI3/Akt/PKB activity predominantly regulates the stability of COX-2 mRNA. Thus,
      Akt/PKB activity is involved in K-Ras-induced expression of COX-2 and
      stabilization of COX-2 mRNA largely depends on the activation of Akt/PKB.

PMID- 11289147
TI  - Genetic pathways in the evolution of morphologically distinct colorectal
      neoplasms.
AB  - Colorectal adenomas can be morphologically classified as exophytic or flat.
      Polypoid cancers and cancers arising de novo (ie., without any adenomatous
      component) might be the results of genetic progression from exophytic and flat
      adenomas, respectively. In this study, we examined 94 morphologically distinct
      neoplastic specimens for mutations in K-RAS and analyzed 10 microsatellite loci
      tightly linked to the tumor suppressor genes APC, p53, DCC/SMAD4, hMSH2, and
      hMLH1. K-RAS mutations were significantly associated with exophytic adenomas [11
      of 21 (52%)] compared to flat adenomas [2 of 13(15%), P < 0.03] and polypoid
      cancers [17 of 25 (68%)] compared to cancers arising de novo [7 of 25 (28%), P <
      0.01]. Two polypoid cancer cases demonstrated three and four different K-RAS
      mutations, respectively, suggesting multiple areas of clonal expansion. Cancers
      arising de novo were significantly associated with loss of heterozygosity (LOH)
      at chromosome 3p compared to pol ypoid cancers [6 of 18(33%) versus 1 of 20(5%),
      P < 0.03], whereas the prevalence of LOH at chromosomes 2p, 5q, 17p, and 18q and
      microsatellite instability were not different between the groups. For all
      cancers, LOH at chromosomes 17p and 18q occurred in 47 and 51%, respectively.
      However, LOH at 17p and 18q occurred in 0 and 16% of benign lesions,
      respectively, suggesting their role in malignant transformation. There was no
      difference in LOH at chromosomes 17p and 18q between exophytic and flat lesions.
      These findings suggest that (a) mutant K-RAS is associated with the exophytic
      growth of colonic neoplasms, and that (b) some colorectal cancers arising de novo
      lose chromosome 3p during their evolution, which is not seen in polypoid cancers.
      Half of all cancers lose chromosomes 17p and 18q at or near the malignant
      transition of benign lesions as reported previously, irrespective of morphology.
      There may be more than one genetic avenue for colorectal cancer formation, and
      this correlates with the morphological characteristics.

PMID- 11289149
TI  - The Ewing's sarcoma gene product functions as a transcriptional activator.
AB  - The Ewing's sarcoma (EWS) proto-oncogene can give rise to a variety of different
      tumors because of the generation of transforming EWS fusion proteins upon
      chromosomal translocation. However, the cellular function of the EWS protein
      itself was hitherto not established. We show that EWS is a nuclear protein, whose
      nuclear localization is dependent upon its transactivating NH2 terminus. EWS COOH
      terminal amino acids suppress this NH2-terminal activation domain in the context
      of a Gal4 fusion protein, which may explain why none of the EWS fusion proteins
      in cancer cells contains the EWS COOH terminus. Furthermore, EWS expression
      enhances c-fos, Xvent-2, and ErbB2 promoter activity in a cell-type-dependent
      manner, indicating that EWS is a transcriptional regulator. Also, the EWS protein
      stimulates transcription mediated by the COOH-terminal transactivation domain of
      the cofactor CREB-binding protein (CBP). Coimmunoprecipitation experiments
      demonstrate that EWS forms a complex with CBP and the homologous p300 protein. A
      COOH-terminal region of EWS is both required for the physical interaction with
      CBP/p300 and sufficient to mediate c-fos activation. In addition, suppression of
      CBP/p300 function by the adenoviral E1A protein abolishes c-fos activation by
      EWS, indicating that EWS-mediated gene regulation depends on CBP/p300. In
      conclusion, the nuclear EWS proto-oncoprotein can function as a transcriptional
      cofactor in conjunction with CBP/p300.

PMID- 11289148
TI  - Gastric cancer and human leukocyte antigen: distinct DQ and DR alleles are
      associated with development of gastric cancer and infection by Helicobacter
      pylori.
AB  - DNA and sera from 130 cases of gastric cancer and 263 population-based controls
      were analyzed to study the association of HLA class II DR-DQ alleles with
      Helicobacter pylori (Hp) infection and the risk for gastric cancer. Presence of
      the DQA1*0102 allele was inversely and significantly associated with Hp
      seropositivity (P = 2 x 10(-5)), which is an independent replication of previous
      findings. However, this inverse relationship with Hp did not correspond with a
      reduced risk of gastric cancer. At the DRB1 locus, the *1601 allele was
      significantly associated with an increased gastric cancer risk with an odds ratio
      (95% confidence interval) of 8.7 (range, 2.7-28.0). The effect of *1601 was more
      pronounced among Hp-negative subjects, and the association was stronger with the
      diffuse, rather than with the intestinal, histological type of gastric cancer.
      Because none of the HLA alleles were associated with both Hp infection and
      gastric cancer, the HLA DR-DQ alleles are linked with gastric cancer risk through
      other mechanisms than an increased susceptibility to Hp infection.

PMID- 11289150
TI  - Placenta growth factor gene expression is induced by hypoxia in fibroblasts: a
      central role for metal transcription factor-1.
AB  - Placenta growth factor (PlGF) is a mitogen for endothelial cells that can
      potentiate the growth and permeabilizing effects on endothelium of vascular
      endothelial growth factor. Here we report that hypoxia induces the expression of
      both PlGF mRNA and protein in immortalized/transformed mouse embryonic
      fibroblasts (mEFs) and in NIH 3T3 cells. Importantly, the magnitude of the
      induction of PlGF expression by hypoxia is enhanced by the presence of oncogenic
      Ras. To investigate the transcriptional component of hypoxia-inducible PlGF
      expression, we cloned and sequenced a 1350-bp fragment of the 5'-flanking region
      of the mouse gene. Analysis of the promoter region indicated the presence of
      putative consensus sequences for known hypoxia-responsive regulatory sites,
      including metal response elements and Sp1-like sites. In the present study, we
      show that the induction of PlGF expression by hypoxia is dependent on the
      presence of the metal response element-binding transcription factor 1 (MTF-1).
      Thus, in mEFs with targeted deletions of both MTF-1 alleles, hypoxia-induced
      increases of PIGF mRNA and protein levels were greatly attenuated compared with
      those in wild-type mEFs. Moreover, transient transfection of a PlGF promoter
      reporter gene into NIH 3T3 cells resulted in hypoxia-responsive transcriptional
      activation of the reporter. Finally, ectopic expression of MTF-1 resulted in
      increased basal transcriptional activity of a PlGF promoter reporter. Together,
      these findings demonstrate that the PlGF gene is responsive to hypoxia and that
      this response is mediated by MTF-1. It remains to be determined whether this
      activation is the result of direct and/or indirect transcriptional activation by
      MTF-1. The stimulatory effect of oncogenic Ras on the induction of PlGF
      expression in hypoxic cells suggests that PlGF could be an important
      proangiogenic factor in the tumor microenvironment.

PMID- 11289151
TI  - Ewing's sarcoma family tumors are sensitive to tumor necrosis factor-related
      apoptosis-inducing ligand and express death receptor 4 and death receptor 5.
AB  - In this study, we investigated the sensitivity of Ewing's sarcoma family tumors
      (ESFTs) of children and adolescents to the tumor necrosis factor-related
      apoptosis-inducing Ligand (TRAIL). TRAIL binds to death receptors (DRs) DR4, DR5,
      DcR1, and DcR2. Either DR4 or DR5 can induce apoptosis, whereas DcR1 and DcR2 are
      considered inhibitory receptors. Nine of 10 ESFT cell lines, including several
      that were Fas resistant, underwent apoptosis with TRAIL through activation of
      caspase-10, capase-8 (FLICE), caspase-3, and caspase-9. In contrast to the Fas
      signaling pathway, caspase-10, but not caspase-8 or the Fas-associated death
      domain-containing molecule, was recruited to the TRAIL receptor-associated
      signaling complex. We found that 9 of 10 ESFT cell lines expressed both DR4 and
      DR5 by Western blotting, whereas the TRAIL-resistant line expressed only DR4.
      However, DR4 was absent from the cell surface in the resistant and two additional
      lines (three of five tested lines), suggesting that it may have been
      nonfunctional. On the contrary, DR5 was located on the cell surface in all four
      sensitive lines tested, being absent only from the cell surface of the resistant
      line that was also DR5-negative by Western blotting. In agreement with these
      findings, the resistance of the line was overcome by restoration of DR5 levels by
      transfection. Levels of DcR1 and DcR2 or levels of the FLICE-inhibitory protein
      (FLIP) did not correlate with TRAIL resistance, and protein synthesis inhibition
      did not sensitize the TRAIL-resistant line to TRAIL. Because these data suggested
      that sensitivity of ESFTs to TRAIL was mainly based on the presence of DR4/DR5,
      we investigated the presence of these receptors in 32 ESFT tissue sections by
      immunohistochemistry. We found that 23 of 32 tumor tissues (72%) expressed both
      receptors, 8 of 32 (25%) expressed one receptor only, and 1 was negative for
      both. Our finding of wide expression of DR4/DR5 in ESFT in vivo, in combination
      with their high sensitivity to TRAIL in vitro and the reported lack of toxicity
      of TRAIL in mice and monkeys, suggests that TRAIL may be a novel effective agent
      in the treatment of ESFTs.

PMID- 11289152
TI  - Tumor necrosis factor alpha induces BID cleavage and bypasses antiapoptotic
      signals in prostate cancer LNCaP cells.
AB  - Survival of cancer cells in response to therapy, immune response, or metastasis
      depends on interactions between pro- and antiapoptotic signals. Two major
      proapoptotic pathways have been described: (a) a death receptor pathway; and (b)
      a mitochondrial pathway. We reported previously that Akt and the epidermal growth
      factor (EGF) receptor send separate, redundant survival signals that act to
      inhibit the mitochondrial proapoptotic pathway in prostate cancer LNCaP cells.
      However, it was unclear at what level the pro- and antiapoptotic signals interact
      in these cells, and it was also unclear whether these signals would inhibit the
      death receptor pathway. We found that EGF can protect LNCaP cells from apoptosis
      induced by LY294002 but not from tumor necrosis factor a (TNF-alpha)-induced
      apoptosis. Furthermore, TNF-alpha induced apoptosis under conditions in which Akt
      was active. Treatment with TNF-alpha resulted in activation of caspase 8 and
      cleavage of BID, which in turn induced cytochrome c release and caspase 9
      dependent activation of effector caspases. Thus, proapoptotic signals induced by
      both TNF-alpha and LY294002 converge on mitochondria and trigger cytochrome c
      release. Because EGF can inhibit cytochrome c release induced by LY294002 but not
      cytochrome c release induced by TNF-alpha, we suggest that the EGF survival
      mechanism operates on the mitochondrial pathway at a site upstream of cytochrome
      c release. The ability of TNF-alpha to bypass survival signals from activated EGF
      receptor and Akt in prostate cancer cells makes death receptor signaling a
      promising avenue for therapeutic intervention.

PMID- 11289153
TI  - Differential expression of cyclooxygenase-2 and its regulation by tumor necrosis
      factor-alpha in normal and malignant prostate cells.
AB  - Cyclooxygenase (COX)-2 expression is elevated in some malignancies; however,
      information is scarce regarding COX-2 contributions to the development of
      prostate cancer and its regulation by inflammatory cytokines. The present study
      compared and contrasted the expression levels and subcellular distribution
      patterns of COX-1 and COX-2 in normal prostate [prostate epithelial cell (PrEC),
      prostate smooth muscle (PrSM), and prostate stromal (PrSt)] primary cell cultures
      and prostatic carcinoma cell lines (PC-3, LNCaP, and DU145). The basal COX-2 mRNA
      and protein levels were high in normal PrEC and low in tumor cells, unlike many
      other normal cells and tumor cells. Because COX-2 levels were low in prostate
      smooth muscle cells, prostate stromal cells, and tumor cells, we also examined
      whether COX-1 and COX-2 gene expression was elevated in response to tumor
      necrosis factor-alpha (TNF-alpha), a strong inducer of COX-2 expression. Northern
      blot analysis and reverse transcription-PCR demonstrated different patterns and
      kinetics of expression for COX-1 and COX-2 among normal cells and tumor cells in
      response to TNF-alpha. In particular, COX-2 protein levels increased, and the
      subcellular distribution formed a distinct perinuclear ring in the normal cells
      at 4 h after TNF-alpha exposure. The COX-2 protein levels also increased in
      cancer cells, but the subcellular distribution was less organized; COX-2 protein
      appeared diffuse in some cells and accumulated as focal deposits in the cytoplasm
      of other cells. TNF-alpha induction of COX-2 and prostaglandin E2 correlated
      inversely with induction of apoptosis. We conclude that COX-2 expression may be
      important to PrEC cell function. Although it is low in stromal and tumor cells,
      COX-2 expression is induced by TNF-alpha in these cells, and this responsiveness
      may play an important role in prostate cancer progression.

PMID- 11289154
TI  - Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small
      cell lung cancer.
AB  - By using mRNA differential display to examine specimens of non-small cell lung
      cancer (NSCLC), we have identified overexpression of dihydrodiol dehydrogenase
      (DDH) that was not detected in the corresponding normal lung tissue. Normally DDH
      is associated with catalysis of polycyclic aromatic hydrocarbons (PAHs) in the
      liver; in NSCLC cells, DDH expression would implicate an association with disease
      progression. In this study we investigated the prognostic significance of DDH
      expression in patients with NSCLC. By using immunohistochemistry, we measured DDH
      expression in 381 patients with NSCLC. The relationship between DDH expression
      and clinicopathological parameters (age, gender, smoking history, mitotic index,
      histological type, stage, cell differentiation, and lymphovascular invasion) was
      analyzed by chi2 analysis. Survival curves were plotted with the method of Kaplan
      Meier, and statistical difference of survivals between different groups was
      compared by a log-rank test. Our results showed that DDH overexpression could be
      detected in 317 (83.2%) of 381 pathological sections and in 77.9% (60 of 77) of
      metastatic lymph nodes. Expression of DDH was confirmed by immunoblotting.
      Compared with patients with DDH overexpression in tumors, patients with low DDH
      expression had significantly lower incidence of early tumor recurrence and
      distant organ metastasis (46.7 versus 29.7%; P = 0.045). Interestingly, survival
      was also significantly better in patients with low DDH expression than in those
      with DDH overexpression (P = 0.0017). Using univariate analysis, we correlated
      three important factors, DDH overexpression, tumor stages, and gender, with poor
      prognosis for NSCLC patients. Nevertheless, biological function and involvement
      of DDH in the disease progression of NSCLC require additional studies.

PMID- 11289155
TI  - Role of carcinoembryonic antigen in the progression of colon cancer cells that
      express carbohydrate antigen.
AB  - Carcinoembryonic antigen (CEA) has been reported to promote the metastatic
      potential in some experimental tumors. Adhesion molecules are known to play an
      important role in the process of metastasis. Cytokines, including interleukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), which are produced
      by Kupffer cells, induce endothelial cells to express adhesion molecules. As a
      result, the present study was designed to investigate whether the interaction
      between CEA and Kupffer cells accelerated the metastatic potential of tumors in
      the liver. Kupffer cells isolated from the liver of male BALB/c mice were
      cultured with CEA, either with or without the addition of a cytokine inhibitor.
      The levels of IL-1beta and TNF-alpha were examined in a culture medium. An
      adhesion assay of colon cancer cell lines to human umbilical vein endothelial
      cells was also performed. When CEA was added to the Kupffer cell culture medium,
      cytokines were produced. Elevated levels of cytokines appeared to lead to
      increased rates of adhesion of cancer cells to endothelial cells. However, these
      phenomena were blocked by the addition of cytokine inhibitors. CEA stimulated
      Kupffer cells to produce cytokines. An elevated number of cytokines have been
      proven to promote the expression of adhesion molecules in endothelial cells.
      These processes are therefore considered to contribute to the metastasis of
      malignant cells to the liver. These results suggest that cytokine inhibitors may
      therefore play an important role in the inhibition of hepatic metastasis.

PMID- 11289156
TI  - Angiogenesis and prostate cancer: identification of a molecular progression
      switch.
AB  - To elucidate the sequence of molecular events intricate with angiogenesis and the
      initiation and progression prostate cancer, the temporal and spatial expression
      patterns of platelet endothelial cell adhesion molecule-1 (PECAM1/CD31), hypoxia
      induced factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF),
      and the cognate receptors VEGFR1 and VEGFR2 were characterized.
      Immunohistochemical and in situ analyses of prostate tissue specimens derived
      from the spontaneous autochthonous transgenic adenocarcinoma of the mouse
      prostate (TRAMP) model identified a distinct early angiogenic switch consistent
      with the expression of PECAM-1, HIF-1alpha, and VEGFR1 and the recruitment of new
      vasculature to lesions representative of high-grade prostatic epithelial
      neoplasia (PIN). During progression of prostate cancer, the intraductal
      microvessel density (IMVD) was also observed to increase as a function of tumor
      grade. Immunoblot and in situ analyses further demonstrated a distinct late
      angiogenic switch consistent with decreased expression of VEGFR1, increased
      expression of VEGFR2, and the transition from a differentiated adenocarcinoma to
      a more poorly differentiated state. Analysis of clinical prostate cancer
      specimens validated the predictions of the TRAMP model. This resolution of
      prostate cancer-associated angiogenesis into distinct early and late molecular
      events establishes the basis for a "progression-switch" model to explain how the
      targets of antiangiogenic therapy might change as a function of tumor
      progression.

PMID- 11289157
TI  - Sublethal irradiation promotes migration and invasiveness of glioma cells:
      implications for radiotherapy of human glioblastoma.
AB  - Human malignant gliomas are highly lethal neoplasms. Involved-field radiotherapy
      is the most important therapeutic measure. Most relapses originate from the close
      vicinity of the irradiated target field. Here, we report that sublethal doses of
      irradiation enhance the migration and invasiveness of human malignant glioma
      cells. This hitherto unknown biological effect of irradiation is p53 independent,
      involves enhanced alphavbeta3 integrin expression, an altered profile of matrix
      metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9) expression
      and activity, altered membrane type 1 MMP and tissue inhibitor of
      metalloproteinases-2 expression, and an altered BCL-2/BAX rheostat favoring
      resistance to apoptosis. BCL-2 gene transfer and irradiation cooperate to enhance
      migration and invasiveness in a synergistic manner. Sublethal irradiation of rat
      9L glioma cells results in the formation of a greater number of tumor satellites
      in the rat brain in vivo concomitant with enhanced MMP-2 and reduced tissue
      inhibitor of metalloproteinases-2 expression. Collectively, these data suggest
      that the current concepts of involved-field radiotherapy for malignant glioma
      need to be reconsidered and that the pharmacological inhibition of migration and
      invasion during radiotherapy may represent a new therapeutic approach to improve
      the therapeutic efficacy of radiotherapy for malignant glioma.

PMID- 11289158
TI  - Restoration of epithelial cell polarity in a colorectal cancer cell line by
      suppression of beta-catenin/T-cell factor 4-mediated gene transactivation.
AB  - Beta-catenin acts as a transcriptional coactivator by forming a complex with T
      cell factor/lymphoid enhancer factor (TCF/LEF) DNA-binding proteins. Aberrant
      transactivation of a certain set of target genes by beta-catenin and TCF4
      complexes has been implicated in familial and sporadic colorectal tumorigenesis.
      A colorectal cancer cell line, DLD-1, becomes irregularly multilayered, when
      maintained confluent for 2-3 weeks, and forms numerous dome-like polypoid foci
      piled-up over the surface of cell sheets. By the use of a strict tetracycline
      regulation system, we found that the continuous suppression of beta-catenin/TCF4
      mediated gene transactivation by dominant-negative TCF4B (deltaN30) reduced these
      piled-up foci and restored a simple monolayer of polarized columnar cells
      resembling normal intestinal epithelium. The restoration of epithelial cell
      polarity was evident in two ways: (a) the formation of microvilli over the apical
      surface; and (b) the distribution of a tight junction protein, ZO-1, to the
      lateral plasma membrane. Retroviral expression of stabilized beta-catenin
      (deltaN89) induced the formation of similar piled-up foci in untransformed IEC6
      intestinal epithelial cells. Sulindac, a nonsteroidal antiinflammatory drug
      effective against colorectal tumorigenesis in familial adenomatous polyposis
      syndrome, suppressed the formation of foci. The loss of epithelial cell polarity
      may be a critical cellular event driving beta-catenin/TCF4-mediated intestinal
      tumorigenesis.

PMID- 11289159
TI  - Soluble decoy receptor 3 is expressed by malignant gliomas and suppresses CD95
      ligand-induced apoptosis and chemotaxis.
AB  - Decoy receptor 3 (DcR3) is a newly identified soluble protein that binds to CD95
      ligand (CD95L) and inhibits its proapoptotic activity. Here we report that DcR3
      is expressed by the majority of long-term and ex vivo malignant glioma cell lines
      as well as in human glioblastoma in vivo. Expression of DcR3 correlates with the
      grade of malignancy: 15 of 18 (83%) glioblastomas (WHO grade IV) but none of 11
      diffuse astrocytomas (WHO grade II) exhibited DcR3 immunoreactivity. We also
      demonstrate that human malignant glioma cells engineered to release high amounts
      of DcR3 into the cell culture supernatant are protected from CD95L-induced
      apoptotic cell death. In contrast, DcR3 does not confer protection from the death
      ligand Apo2 ligand (TRAIL). Importantly, ectopic expression of DcR3 resulted in
      substantial differences in immune cell infiltration in the 9L rat gliosarcoma
      model. Thus, the infiltration of CD4+ and CD8+ T cells as well as
      microglia/macrophages into glioma was substantially decreased in DcR3-producing
      tumors compared with control tumors. Chemotaxis assays revealed that DcR3
      counteracts the chemotactic activity of CD95L against microglial cells in vitro.
      These findings suggest that DcR3 may be involved in the progression and immune
      evasion of malignant gliomas.

PMID- 11289160
TI  - Catalase-overexpressing thymocytes are resistant to glucocorticoid-induced
      apoptosis and exhibit increased net tumor growth.
AB  - Glucocorticoids are used for the treatment of lymphoid neoplasms, taking
      advantage of the well-known ability of these compounds to cause apoptosis in
      lymphoid tissues. Previously, we have shown that dexamethasone, a synthetic
      glucocorticoid, causes a down-regulation of several antioxidant defense enzymes
      and proteins, including catalase and thioredoxin, concomitant with the induction
      of apoptosis in WEHI7.2 mouse thymoma cells. To test whether this down-regulation
      plays a critical role in the mechanism of steroid-induced apoptosis, WEHI7.2
      cells were transfected with rat catalase. Two clones, expressing 1.4-fold and 2.0
      fold higher catalase specific activity, respectively, when compared with
      vectoronly transfectants were selected for further study. An increase to 1.4-fold
      parental cell catalase activity delayed cell loss after dexamethasone treatment,
      whereas a 2.0-fold parental catalase activity prevented dexamethasone-induced
      cell loss for 48 h after treatment. Dexamethasone treatment of the WEHI7.2 cells
      stimulated a release of cytochrome c into the cytosol. Catalase-overexpressing
      cells showed a delay or lack of cytochrome c release from the mitochondria, which
      correlated temporally with the delay or prevention of cell loss in the culture
      after dexamethasone treatment. A decreased amount of cell death from WEHI7.2
      cells overexpressing catalase was also seen in tumor xenografts in severe
      combined immunodeficient mice when compared with tumors from vector-only
      transfected cells. Similarly, thioredoxin-overexpressing WEHI7.2 cells, shown
      previously to be apoptosis resistant, showed decreased cell death in tumor
      xenografts. This resulted in larger tumors from cells overexpressing these
      proteins. Cell death in control transfectant tumor xenografts was primarily
      attributable to apoptosis. In contrast, the cell death we observed in tumors from
      thioredoxin- or catalase-overexpressing cells had a higher frequency of a
      nonapoptotic, nonnecrotic type of cell death termed para-apoptosis. These data
      suggest that: (a) oxidative stress plays a critical role in steroid-induced
      apoptosis prior to the commitment of the cells to undergo apoptosis; and (b)
      resistance to oxidative stress can contribute to tumor growth.

PMID- 11289162
TI  - Loss of cyclin D2 expression in the majority of breast cancers is associated with
      promoter hypermethylation.
AB  - Cyclin D2 is a member of the D-type cyclins, implicated in cell cycle regulation,
      differentiation, and malignant transformation. It was noted previously that
      cyclin D2 is not expressed in the majority of breast cancer cell lines, whereas
      abundant expression was detected in finite life span human mammary epithelial
      cells. By reverse transcription-PCR and Western blot analysis, we extended this
      finding to primary breast carcinomas and show that the majority of these tumors
      lack expression of cyclin D2 mRNA (18 of 24) and protein (10 of 13). In contrast,
      both luminal and myoepithelial subpopulations of normal breast tissues expressed
      cyclin D2. Hypermethylation of the CpG island in the promoter was detected by
      methylation-specific PCR in nearly half of the breast cancers (49 of 106) and was
      associated with silencing of cyclin D2 gene expression. Promoter hypermethylation
      was also detected in ductal carcinoma in situ, suggesting that loss of cyclin D2
      expression is an early event in tumorigenesis. Our results suggest that loss of
      cyclin D2 expression is associated with the evolution of breast cancer.

PMID- 11289161
TI  - Reduced levels of retinyl esters and vitamin A in human renal cancers.
AB  - Clinical and preclinical studies suggest that retinoids can inhibit the growth of
      a small percentage of human renal cancers (RCs), although the majority of RCs
      both in vitro and in vivo are retinoid resistant. Our recent studies indicate
      that the metabolism of retinol to retinyl esters is greatly reduced in human
      carcinoma cell lines of the oral cavity, skin, and breast as compared with their
      normal epithelial counterparts, suggesting that human carcinoma cells are
      retinoid deficient relative to normal epithelial cells. We considered whether
      retinoid resistance in RCs was related to an abnormality in retinoid metabolism.
      The metabolism of [3H]retinol and of [3H]retinoic acid (RA) was examined in RC
      cell lines and normal human kidney (NK) epithelial cells cultured in media, in
      RA, or in RA plus IFN-alpha. The expression of LRAT (lecithin:retinol
      acyltransferase) was assessed by Northern and Western analysis. Retinol and
      retinyl ester levels were determined in tissue samples of normal human kidney and
      renal cell carcinoma. NK cells esterified all of the 50 nM [3H]retinol in which
      they were cultured. In contrast, six of the seven RC cell lines metabolized only
      trace amounts of [3H]retinol to [3H]retinyl esters. Consistent with this relative
      lack of [3H]retinol esterification by the tumor cells, the tumor cells exhibited
      LRAT transcripts of aberrantly low sizes relative to those in normal epithelial
      cells. Moreover, the NK cells expressed abundant levels of LRAT protein by
      Western analysis, whereas the RC cells did not express LRAT protein. When samples
      of human kidney tumor tissue were compared with samples of normal kidney tissue
      from patients who had undergone surgery for primary RC, the normal kidney tissues
      contained much higher levels of retinol and retinyl esters (approximately 0.5-2
      microg/gram wet weight) than the tumor tissues in all seven patients examined.
      Culture of the RC lines in IFN-alpha plus all-trans-RA, a combination therapy
      used clinically, resulted in higher intracellular levels of [3H]retinol and
      [3H]retinyl esters. The metabolism of [3H]RA was also examined in these RC lines
      versus NK cells. Although the NK epithelial cells metabolized [3H]RA, the
      majority of the RC lines metabolized [3H]RA at a much slower rate. Most of the RC
      lines metabolized only 10-30% of the 50 nM [3H]RA over 6 h of culture. These data
      indicate that RCs both in vitro and in vivo are retinol and retinyl ester
      deficient relative to the normal human kidney, and they suggest that the aberrant
      differentiation of the neoplastic renal cells results in part from a defect in
      retinoid metabolism.

PMID- 11289163
TI  - The twentieth international symposium of the Sapporo Cancer Seminar Foundation:
      gene environment interaction and cancer prevention.
AB  - The main goal of this Symposium was to discuss new information that could be used
      for the development of effective and novel approaches in cancer prevention.
      Mounting evidence indicates that genetic predisposition to cancer plays an
      important role in the etiology of the disease and that multistage carcinogenesis
      is for the most part based on multiple genetic changes, favoring cell survival.
      It is also evident that a variety of environmental factors lead to carcinogenic
      changes and determine cancer-causative or cancer-facilitative genetic changes;
      these factors may be endogenous in origin, as for example those that are
      endocrinologic in nature, or may come from the external environment, as for
      example products in tobacco smoke or in industrial pollution. It is therefore
      obvious that gene-environment interactions play a pivotal role in carcinogenesis
      and consequently may offer specific sites of intervention that may be useful for
      the development of cancer prevention. In general, cancer prevention can be
      implemented through Public Health measures, as is typically the case for
      intervention on smoking, industrial pollution, aflatoxin B contamination or, when
      we know more about it, dietary habits. On the other hand, it should become
      possible to design more rational chemoprevention and immunoprevention trials as
      more becomes known about the genetic changes predisposing to cancer and about the
      gene products that are responsible for the phenotypic changes leading to
      neoplasia.

PMID- 11289164
TI  - Partners in the prevention of facial injuries.

PMID- 11289165
TI  - Outcomes of open versus closed treatment of mandibular subcondylar fractures.
AB  - OBJECTIVES: The purpose of this study was to compare the long-term treatment
      results of open reduction and rigid internal fixation (ORIF) with closed
      reduction and maxillomandibular fixation (CRMMF) for subcondylar fractures when
      guided by specific indications and contraindications. PATIENTS AND METHODS: A
      protocol for the treatment of condylar process fractures was developed that
      included absolute and relative indications and contraindications as well as a
      technique regimen. To evaluate the results of this protocol, 10 patients treated
      with CRMMF and 10 treated by ORIF were recalled after a minimum of 6 months and
      examined for gender, race, diagnosis, age at injury, time since operation, and
      cause of the fracture. Each group was assessed by 2 blinded investigators for
      maximum interincisal opening, right lateral excursion, left lateral excursion,
      protrusive movement, deviation on opening, scar perception, motor function,
      sensory perception, contour perception, occlusion, and perception of pain.
      Nonparametric data were compared for statistical significance with a chi-square
      analysis and parametric data with an independent samples t-test (P < .05).
      RESULTS: No statistically significant differences existed between the ORIF and
      CRMMF groups for gender, race, diagnosis, or cause. Moreover, no differences
      existed for age at injury, maximum interincisal opening, right lateral excursion,
      left lateral excursion, protrusive movement, deviation on opening, or occlusion.
      Differences were noted between groups for time since operation, scar perception,
      and perception of pain. Using the protocol outlined, there were no differences
      between the ORIF and CRMMF groups for ranges of motion, occlusion, contour, and
      motor or sensory function. The ORIF group was associated with perceptible scars.
      The CRMMF group was associated with chronic pain. CONCLUSIONS: Using a treatment
      protocol, there were few differences in outcomes between patients treated with
      CRMMF and ORIF for subcondylar fractures.

PMID- 11289166
TI  - Patient's perception of the facial appearance after maxillomandibular advancement
      for obstructive sleep apnea syndrome.
AB  - PURPOSE: The goal of this study was to evaluate the patient's perception of the
      facial appearance after maxillomandibular advancement (MMA) surgery for
      obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: During a 14-month
      period, 58 patients underwent MMA for OSAS. All of the patients underwent
      preoperative and postoperative cephalometric analysis. Between 6 and 12 months
      after surgery, a questionnaire was mailed to each patient. The questionnaire
      asked the patient to evaluate subjectively their postoperative facial appearance.
      Visual analog scale ([VAS] 0 to 10) was used to assess the extent of the facial
      changes. RESULTS: Forty-four (76%) patients (39 men, 6 women) responded to the
      questionnaire. Cephalometric analysis revealed that 40 patients had
      maxillomandibular protrusion postoperatively. Forty-two (96%) of the 44 patients
      reported changes in their facial appearance (VAS, 4.8 +/- 2.5). Twenty-four (55%)
      patients reported favorable facial changes (ie, they were more attractive [15
      patients] and/or more youthful). Fourteen patients gave neutral responses (ie,
      they were no more or no less attractive). Four patients gave unfavorable
      responses (ie, they were less attractive after surgery). CONCLUSION: The results
      suggest that most patients who underwent MMA for OSAS noted moderate changes in
      their facial appearance. Despite significant maxillomandibular protrusion based
      on the postoperative cephalometric analysis, more than 90% of the patients gave
      either positive or neutral responses to the changes in their facial appearance.

PMID- 11289167
TI  - The effect of sex and age on facial asymmetry in healthy subjects: a cross
      sectional study from adolescence to mid-adulthood.
AB  - PURPOSE: The study assessed the effects of sex and age on 3-dimensional (3D) soft
      tissue facial asymmetry. PATIENTS AND METHODS: The 3D coordinates of selected
      soft-tissue facial landmarks were digitized on 314 healthy white subjects (40
      male and 33 female adolescents, aged 12 to 15 years; 73 female and 89 male young
      adults, aged 18 to 30 years; and 41 male and 38 female adults, aged 31 to 56
      years) by an electromagnetic instrument. Facial asymmetry was quantified by
      detecting a plane of symmetry and the centers of gravity of the right and left
      hemifaces and by calculating the distance between the 2 centers of gravity
      (distance from the symmetry [DFS]). Both absolute (millimeters) and percentage
      (of the nasion-center of gravity distance) DFS were obtained, as well as the
      maximum normal asymmetry. The asymmetry of single landmarks was also quantified.
      RESULTS: No gender- or age-related differences were found for both absolute and
      percentage DFS (P > .05). The maximum normal asymmetry was slightly greater in
      females than in males of corresponding age; within each sex, the largest values
      were found in the adolescent group. Tragion, gonion, and zygion were the most
      asymmetric landmarks in all groups (about 10% to 12% of the nasion-facial center
      of gravity distance), whereas the least asymmetric was endocanthion (4% to 6%).
      CONCLUSIONS: A slight soft-tissue facial asymmetry was found in normal subjects.
      The maximum normal asymmetry could be useful in identifying borderline asymmetric
      patients.

PMID- 11289168
TI  - Bite forces after open or closed treatment of mandibular condylar process
      fractures.
AB  - PURPOSE: This study compared maximum voluntary bite forces in patients who
      received either open or closed treatment for fractures of the mandibular condylar
      process. PATIENTS AND METHODS: One hundred fifty-five patients (127 male, 28
      female) with unilateral fractures of the mandibular condylar process (91 treated
      closed and 64 treated open) were included in this study. Maximum voluntary bite
      forces were measured at 6 weeks, 6 months, and 1, 2, and 3 years after fracture.
      At each trial, unilateral maximum voluntary bite force was measured at 4
      different tooth positions bilaterally using a standard transducer.
      Electromyography (EMG) of the masseter muscles was also recorded during the bite
      force measurements, and ratios of the working/balancing side EMG were calculated.
      Analysis of the data was performed using standard statistical methods. RESULTS:
      The only significant difference between the 2 samples was in the level of
      fractures on the condylar process. No patients treated open had fractures of the
      "head" of the condylar process, whereas there were 11 in the group treated
      closed. No differences were observed in maximum voluntary bite forces between the
      2 treatment groups at any time period, or were there correlations between bite
      force magnitude and location of the fracture, displacement of the fracture, or
      any other variable studied. Both groups showed a significant recovery of maximum
      bite force from the 6-week to the 6-month testing session. For both groups,
      working/balancing EMG ratios were significantly greater when subjects were biting
      on the side opposite the fracture. When biting on that side, the
      working/balancing EMG ratios were higher in the closed treatment group, but the
      difference did not reach significance. CONCLUSIONS: Maximum voluntary bite forces
      in patients treated for mandibular condylar process fractures do not differ
      significantly when treatment is open or closed. Neuromuscular adaptations to the
      fractured mandibular condylar process occur in both groups.

PMID- 11289169
TI  - Upper lip asymmetry in adults during smiling.
AB  - PURPOSE: This study examined the incidence of upper lip asymmetry in adults while
      smiling. PATIENTS AND METHODS: Two-hundred ten students between the ages of 21
      and 44 years were examined. Subjects determined to have an occlusal plane cant
      were eliminated from the study. Repeated smiles were then evaluated in the
      remaining subjects to check for upper lip asymmetry. RESULTS: Fifteen subjects
      were observed to have occlusal plane cants and were eliminated from the study. Of
      the remaining 195 subjects, 17 (8.7%) were found to have an asymmetrical smile
      secondary to canting of the upper lip. CONCLUSIONS: Although there was not a high
      incidence, the results of this study indicate there is clinically evident upper
      lip canting associated with smiling in the adult population that needs to be
      considered in patients undergoing orthognathic and cosmetic surgery.

PMID- 11289170
TI  - The staircase technique for treatment of cancer of the lower lip: a report of 36
      cases.
AB  - PURPOSE: This article reports the authors' experience with treatment of lower lip
      cancer using the staircase technique. PATIENTS AND METHODS: Thirty-six patients
      with stage T1 or T2 cancers of the lower lip were treated. RESULTS: No
      recurrences were observed during a 6- to 32-month follow-up. All patients showed
      excellent aesthetic results and no microstomia. CONCLUSIONS: The staircase
      technique can be used to close defects of up to two thirds of the lower lip. Two
      bilateral symmetric flaps are used for median defects; 2 bilateral asymmetric
      flaps are used for paramedian defects greater than 20 mm; and only 1
      contralateral flap is required for paramedian defects up to 20 mm.

PMID- 11289171
TI  - A computer study of biodegradable plates for internal fixation of mandibular
      angle fractures.
AB  - PURPOSE: This computer-based study was performed to determine the suitability of
      small biodegradable plate systems for mandibular angle fractures. MATERIALS AND
      METHODS: In a 3-dimensional computer model of the mandible, fracture mobility and
      plate strain were calculated for bite forces applied on 13 bite points on the
      dental arch. The angle fracture was fixed with 2 polylactide (PLA) midiplates or
      with 2 PLA maxiplates. The first plate was positioned buccally on the external
      oblique ridge. Two positions of the second plate were studied: halfway up the
      height of the mandible or on the lower border. Maximum fracture mobility was set
      at a limit of 150 microm to enable undisturbed fracture healing. Maximum plate
      strain was set at the yield strain of PLA. RESULTS: Fixation with the PLA
      maxiplates, with the second plate positioned halfway up the height of the
      mandible, resulted in fracture mobility below the set limit for all bite points.
      For the other PLA fixation strategies, fracture mobility exceeded the set limit.
      Fixation with the second plate positioned halfway up the height of the mandible
      generally resulted in less fracture mobility than with the plate positioned on
      the lower border. The yield strain of PLA was not exceeded in any of the fixation
      strategies. CONCLUSIONS: Based on the computer model, 2 PLA maxiplates are
      suitable for fixation of mandibular angle fractures. One plate should be
      positioned buccally on the external oblique ridge, and the other should be
      positioned halfway up the height of the mandible.

PMID- 11289172
TI  - The effect of rim mandibulectomy configuration and residual segment size on
      postoperative fracture risk: an in vitro study.
AB  - PURPOSE: This study evaluated the effect that size and shape of rim
      mandibulectomy has on residual mandibular strength and resistance to fracture,
      with the ultimate goal of improving the use of this technique and establishing a
      threshold for the application of prophylactic internal fixation. MATERIALS AND
      METHODS: Ten partially dentate dry human mandibles were mounted in a manner
      replicating the pterygomasseteric musculature. Unilateral midbody serial rim
      excisions of increasing size were completed in both a curvilinear and right
      angled fashion, and physiologic forces were gradually applied to a level of
      residual segment fracture. Dimensional measurements were taken of the specimens
      before and after fracture to understand which factors contributed to failure.
      RESULTS: On average, a curvilinear excision configuration resisted higher
      occlusal forces with a smaller residual segment than did the right-angled
      excision configuration. A residual inferior border thickness of less than 9 mm
      could not predictably withstand force application within the limits of the
      experimental model. CONCLUSION: These data support the use of a curvilinear
      excision configuration for rim mandibulectomies. Reproducibility of the location
      of the residual segment failure and other consistent residual segment dimensional
      information have implications regarding the limitations of this technique, beyond
      which the use of adjunctive support in the form of maxillomandibular fixation or
      prophylactic internal fixation may be indicated.

PMID- 11289173
TI  - Management of the oral and maxillofacial surgery patient with thrombocytopenia.
AB  - Patients with disorders of coagulation and bleeding can be among the most
      challenging surgical patients to manage. Intraoperative or postoperative bleeding
      can contribute to life-threatening complications in even the most "benign"
      surgical procedures. An adequate number and function of platelets play a critical
      role in the coagulation pathway. A thorough understanding of platelet physiology
      and platelet disorders is therefore essential in the management of the
      thrombocytopathic oral and maxillofacial surgery patient. A careful preoperative
      evaluation will help the surgeon treat these patients and help prevent
      potentially catastrophic intraoperative or postoperative bleeding.

PMID- 11289174
TI  - Harvard Dental School and the fight for "the ideals of democracy".

PMID- 11289175
TI  - Metachronous bilateral metastases of  renal cell carcinoma to the parotid region.

PMID- 11289176
TI  - Juvenile active ossifying fibroma of the mandible: a report of 2 cases.

PMID- 11289178
TI  - Cervicofacial actinomycosis following orthognathic surgery: report of 2 cases.

PMID- 11289177
TI  - Bilateral submandibular duct atresia: case report.

PMID- 11289179
TI  - Hemangiopericytoma of the buccal region: a case report.

PMID- 11289180
TI  - Acyclovir treatment in 2 patients with benign trigeminal sensory neuropathy.

PMID- 11289181
TI  - Squamous cell carcinoma of the maxilla during pregnancy: report of  case.

PMID- 11289183
TI  - Giant apocrine cystadenoma of the preauricular region.

PMID- 11289182
TI  - Asystole secondary to venipuncture: report of  case.

PMID- 11289184
TI  - Gingival metastases as first sign of a primary uterine angiosarcoma.

PMID- 11289185
TI  - "Infantile" myofibroma of the oral cavity: report of  case.

PMID- 11289186
TI  - A tribute to Victor Matukas.

PMID- 11289187
TI  - The cause of submandibular duct dilation in the newborn.

PMID- 11289188
TI  - What is a learning portfolio?

PMID- 11289189
TI  - Hypoglycaemia unawareness: a reversible problem?

PMID- 11289190
TI  - ACE inhibition and renovascular disease.

PMID- 11289191
TI  - Islet cell transplantation and  type 1 diabetes mellitus.

PMID- 11289192
TI  - Human papillomavirus: a highly prevalent sexually transmitted disease agent among
      female sex workers from Mexico City.
AB  - BACKGROUND: Cervical cancer, a human papillomavirus (HPV)-caused neoplasia, is
      highly prevalent in Mexico. GOAL: To determine the prevalence of HPV infection in
      female sex workers (FSW) from Mexico City and to assess the association between
      HPV infection and the characteristics of these women. STUDY DESIGN: A
      questionnaire was applied to 495 FSW. Cervical cell specimens were obtained for
      DNA amplification and hybridization to detect 27 HPV types. A risk factor
      analysis was performed. RESULTS: The overall prevalence of HPV infection was
      48.9%. The prevalence of high-risk HPV types was 43%, whereas that of low-risk
      types was 24.6%. A total of 18.8% of study participants was infected with both
      high-risk and low-risk HPV types, and 28.5% were infected with two or more HPV
      types. Younger age and failure to use a condom were independently associated HPV
      risks (odds ratio, 7.3 and 2.3; 95% CI, 3.5-15.0 and 1.2-4.4, respectively).
      CONCLUSIONS: Infection with high-risk and multiple HPV types is high among
      Mexican FSW. This study corroborated a higher infection rate in younger women. A
      higher risk of HPV infection is also observed in women who have been involved
      with sex work for less than 1 year. However, condom use showed a protective
      effect against HPV infection.

PMID- 11289193
TI  - Syphilis outbreak assessment.
AB  - BACKGROUND: Syphilis rates began to decline in 1991 and have decreased every year
      since. In 1998, 6,993 cases of primary and secondary syphilis were reported in
      the United States, for a national incidence of 2.6 cases per 100,000 population.
      Although syphilis rates are at an historic low, focal outbreaks still occur. On
      October 7, 1999, the Division of Sexually Transmitted Disease Prevention of the
      Centers for Disease Control and Prevention, in collaboration with federal and
      community partners, presented the National Plan for Elimination of Syphilis from
      the United States. One of the five key strategies of the plan is rapid outbreak
      response. METHODS: Methods for outbreak assessment and response were reviewed in
      the literature, synthesized, and adapted for use in syphilis outbreaks. RESULTS:
      Key elements of outbreak assessment and response are detection, surveillance data
      review, hypothesis generation, intervention development, and the evaluation of
      clinical, public health, and laboratory services. CONCLUSIONS: Outbreak response
      necessitates community participation and a coordinated interdisciplinary effort
      to determine social and behavioral contributors to the outbreak and to develop
      targeted interventions.

PMID- 11289194
TI  - Single-dose gatifloxacin compared with ofloxacin for the treatment of
      uncomplicated gonorrhea: a randomized, double-blind, multicenter trial.
AB  - BACKGROUND: Treatment of gonorrhea is complicated by widespread resistance of
      Neisseria gonorrhoeae to antimicrobial agents of choice, including decreased
      susceptibility to ciprofloxacin. GOAL: To demonstrate the efficacy and safety of
      gatifloxacin, a novel 8-methoxy fluoroquinolone antibiotic, compared with
      ofloxacin in treating patients with uncomplicated gonococcal infection. STUDY
      DESIGN: In a double-blind, randomized (2:2:1), controlled trial, 340 men and 388
      women with uncomplicated gonorrhea who were 16 years or older received a single
      oral dose of gatifloxacin (400 mg or 600 mg) or ofloxacin (400 mg). Primary
      analysis of efficacy was based on bacteriologic eradication from sites of
      infection. Secondary analyses examined clinical response and adverse event
      profiles. RESULTS: Bacteriologic eradication rates for gatifloxacin in evaluable
      men with urethral gonorrhea were 99% (400 mg) and 100% (600 mg) versus 100% for
      ofloxacin (n = 117, 122, and 55, respectively; P = ns). Eradication rates in
      evaluable women with endocervical gonorrhea were 99% for both 400 mg and 600 mg
      gatifloxacin versus 100% for ofloxacin (n = 101, 104, and 55, respectively; P =
      ns). Eradication rates were 100% for both rectal (n = 43) and pharyngeal (n = 31)
      infection across all treatment groups. All three drug regimens were well
      tolerated and exhibited similar clinical response profiles. CONCLUSION:
      Gatifloxacin is safe and effective as a single 400-mg or 600-mg dose for the
      treatment of uncomplicated gonorrhea. Similar efficacy rates were observed with
      the 400-mg and 600-mg doses. A single 400-mg dose can be recommended for
      treatment of uncomplicated gonorrhea.

PMID- 11289195
TI  - Domestic violence reported by women attending a sexually transmitted disease
      clinic.
AB  - BACKGROUND: Domestic violence occurs across all social, demographic, and economic
      strata of society, though women who report it are disproportionately young,
      unmarried, live with a male friend or family member other than a husband, engage
      in substance abuse, and are poor. GOAL: To assess the prevalence of domestic
      violence among a sample of women presenting for care at a sexually transmitted
      disease (STD) clinic, and to identify behavioral and clinical correlates of
      domestic violence in this group. STUDY DESIGN: Women attending an inner-city STD
      clinic were asked to complete a self-administered questionnaire that ascertained
      demographic, clinical, and behavioral information. Questions regarding recent and
      lifetime physical and verbal abuse by a social intimate were included. Standard
      diagnostic tests and therapy for a variety of genitourinary infections were
      provided when indicated as a matter of routine care. RESULTS: Three hundred and
      seventy-five female clinic attendees completed the questionnaire. One hundred and
      forty one (37.6%) women reported ever having experienced physical assault by an
      intimate, and 123 (32.8%) reported verbal threats of violence. Fifty-eight
      (15.5%) women reported at least one episode of physical abuse in the year
      preceding participation. A report of physical violence was associated with drug
      use, STD history, and a history of a serious medical condition (P < 0.05).
      CONCLUSION: The high prevalence of domestic violence among women seeking care at
      an inner-city STD clinic suggests that these sites may be important for the
      detection of abuse victims. Clinic staff should be trained to inquire about
      domestic violence. On-site or referred resources (e.g., legal, social, clinical)
      should be made available to these women.

PMID- 11289196
TI  - Hepatitis B vaccination in sexually transmitted disease (STD) clinics: a survey
      of STD programs.
AB  - BACKGROUND: Hepatitis B virus infection causes substantial morbidity and
      mortality in the United States. Sexual activity is the most commonly reported
      risk factor among persons with acute hepatitis B, yet hepatitis B vaccine
      coverage among adolescents and adults with high-risk sexual practices is low.
      Sexually transmitted disease (STD) clinics are potentially efficient settings for
      vaccine administration to persons with high-risk sexual practices; however,
      little is known about hepatitis B vaccination activities in these settings. GOAL:
      To gain information about policies and activities for vaccinating against
      hepatitis B in STD clinic settings. STUDY DESIGN: In April 1997, a questionnaire
      was sent to managers of 65 federally funded STD programs in state and local
      health departments. A similar survey was sent to 89 STD clinic managers in
      November 1997. RESULTS: The response rate among program managers was 97% (63/65).
      Forty-eight percent considered hepatitis B prevention a program responsibility;
      21% had developed and distributed written policies to prevent hepatitis B through
      vaccination; and 27% had developed policies to encourage hepatitis B education
      activities. The response rate among clinic managers was 82% (73/89). Forty-five
      percent reported that their STD clinics had implemented policies recommending
      hepatitis B vaccination and health education activities. Program managers and
      clinic managers reported that lack of funding to cover the cost of the vaccine,
      and lack of resources to provide prevaccination counseling, administer vaccine,
      and track clients for vaccine series completion were the primary barriers to the
      implementation of hepatitis B vaccination programs. CONCLUSIONS: To enhance
      hepatitis B vaccination in STD clinics, existing funding sources must be accessed
      more effectively. Supplemental funding mechanisms for the cost of vaccine and
      resources for implementing vaccination programs also need to be identified.
      Additionally, STD clinics and programs should continue to propose and implement
      hepatitis B vaccination policies.

PMID- 11289197
TI  - Screening for Chlamydia trachomatis in an anonymous and confidential HIV
      counseling and testing site: feasibility and prevalence rates.
AB  - BACKGROUND: Chlamydia trachomatis is the most common bacterial sexually
      transmitted disease (STD) in the United States. The development of nucleic acid
      amplification tests for C trachomatis in urine specimens allows for screening
      outside traditional clinic settings. Persons visiting an HIV counseling and
      testing site may be at increased risk for STDs, including C trachomatis. GOAL: To
      measure the acceptance of C trachomatis urine screening and the prevalence of C
      trachomatis infection among clients at an HIV counseling and testing site. STUDY
      DESIGN: Site HIV counselors offered urine C trachomatis screening to clients,
      administered a questionnaire, and collected urine samples. RESULTS: Of 808
      counseling and testing site clients approached for C trachomatis screening, 572
      (71%) accepted. The most common reasons for declining screening were absence of
      symptoms (33%) and recent STD testing (32%). Men were more likely to accept urine
      screening than women (risk ratio, 1.31; 95% CI, 1.06-1.62), as were clients who
      practiced oral sex, had a history of STD, or who had never been screened for STD.
      Of 560 urine specimens processed, only 8 (1.43%; 95% CI, 0.66-2.91%) were
      infected with C trachomatis. CONCLUSIONS: Sites offering HIV testing and
      counseling are a feasible alternative to clinical settings for C trachomatis
      screening. Prevalence may be too low for screening to be cost effective unless
      higher-risk subpopulations can be identified.

PMID- 11289198
TI  - Clinical manifestations of early syphilis by HIV status and gender: results of
      the syphilis and HIV study.
AB  - BACKGROUND: Despite reports of unusual clinical presentations and therapeutic
      responses among HIV-infected patients with syphilis, syphilis has not been
      regarded as a serious opportunistic infection that predictably progresses among
      most HIV-coinfected patients. GOAL: To define and describe differences in the
      presentation and response to treatment of early syphilis among HIV-infected and
      HIV-uninfected patients, to describe any differences by gender, and to determine
      if clinical presentation of central nervous system involvement predicted
      serologic failure. DESIGN: A prospective, multicenter, randomized, controlled
      trial of enhanced versus standard therapy to compare the benefit of enhanced
      therapy, the clinical importance of central nervous system involvement, and the
      clinical manifestations of early syphilis infection among HIV-infected and HIV
      uninfected patients. RESULTS: The median number of ulcers was significantly
      greater among HIV-infected and HIV-uninfected patients, as was the percent of HIV
      infected patients with multiple ulcers. Among patients diagnosed with secondary
      syphilis, a higher percentage of HIV-infected patients presented with genital
      ulcers [13/53 (25%)] than did HIV-uninfected patients [27/200 (14%)]. No
      differences between HIV-infected and HIV-uninfected patients were detected for
      other secondary syphilis manifestations. Although women presented more frequently
      with secondary syphilis than did men, no other gender differences in clinical
      manifestations were noted. Neurologic complaints were reported most frequently
      among patients with secondary syphilis [103/248 patients (42%)] compared with
      patients with primary syphilis [32/136 (24%)] and early latent syphilis [48/ 142,
      (34%)] (P < 0.05), but no differences in neurologic complaints were apparent by
      HIV status or CSF abnormalities. No neurologic complaints were significantly
      associated with serologic treatment failures at 6 months. CONCLUSIONS: Overall,
      HIV infection had a small effect on the clinical manifestations of primary and
      secondary syphilis. Compared with HIV-uninfected patients, HIV-infected patients
      with primary syphilis tended to present more frequently with multiple ulcers, and
      HIV-infected patients with secondary syphilis presented with concomitant genitals
      ulcers more frequently.

PMID- 11289199
TI  - Screening for chronic hepatitis B and C virus infections in an urban sexually
      transmitted disease clinic: rationale for integrating services.
AB  - BACKGROUND AND OBJECTIVES: Clients attending sexually transmitted disease (STD)
      clinics are at risk for multiple infections (e.g., STDs, HIV, and infectious
      viral hepatitis). Risk assessment and serosurveys can document the need for
      hepatitis screening and vaccination services. GOAL: To determine hepatitis C and
      B virus seroprevalence, identify predictive risk factors, and provide a rationale
      for integrating hepatitis services in an STD clinic. METHODS: During various
      periods in 1998, consecutive clients completed a self-administered risk
      assessment and were offered screening for markers of hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infection (HBV core antibody and anti-HCV [enzyme-linked
      immunosorbent assay 3.0, confirmed by recombinant immunoblot assay 2.0]).
      RESULTS: Sixteen percent of 300 clients tested for an anti-HBV core were
      positive, with injecting-drug users (IDUs) and men who have sex with men (MSM)
      having higher prevalences (50% and 37%, respectively). Of 615 clients tested for
      anti-HCV, 21 (3.4%) were positive. Injecting-drug users (n = 34) had a 38% anti
      HCV prevalence compared with 1.1% for non-IDUs. Of 66 non-IDU MSM tested, none
      was HCV infected. IDUs had a high prevalence of past STDs (> 50%) and unsafe
      sexual behavior. CONCLUSIONS: Injecting drug users and MSM are at high risk for
      STDs, HIV, and hepatitis infections and could benefit from a "one-stop" STD
      clinic that included hepatitis prevention services.

PMID- 11289200
TI  - Level of AIDS and HIV knowledge and sexual practices among sexually transmitted
      disease patients in China.
AB  - BACKGROUND: Little is known about sex practices that increase the risk of
      contracting HIV infection or the level of HIV and AIDS knowledge among sexually
      transmitted disease (STD) patients in China. OBJECTIVE: To describe AIDS and HIV
      knowledge, sexual practices, and factors associated with never using condoms
      among patients at an STD clinic in Jinan, China. STUDY DESIGN: Clinic patients (n
      = 498) were randomly sampled to answer AIDS and HIV knowledge questions and to
      report sexual practices, including condom use. RESULTS: Patients had low levels
      of AIDS and HIV knowledge and engaged in high-risk sex behaviors. The majority of
      patients reported having had multiple sex partners. When having sex, few men and
      no women reported always using condoms. Gender, age, residence, AIDS and HIV
      knowledge, and having multiple sex partners were significantly associated with
      never using condoms. CONCLUSION: STD clinic patients report having engaged in
      high-risk sex behaviors. More research is needed to better understand the factors
      relevant to developing risk-reduction interventions for these patients in China.

PMID- 11289201
TI  - Seroepidemiology of human herpesvirus 8 among young men who have sex with men.
AB  - BACKGROUND: The modes of transmission of human herpesvirus 8 (HHV-8) remain
      unclear. GOAL: To study HHV-8 seroprevalence and risk factors among young men.
      STUDY DESIGN: The Young Men's Survey was a multisite cross-sectional HIV
      seroprevalence and behavioral risk survey of men aged 15 to 22 years who attended
      public venues frequented by young men who have sex with men (MSM). Blood
      specimens were tested for HHV-8 by using an immunofluorescence assay at a 1:40
      dilution among 488 participants in Seattle-King County, WA. RESULTS: Total HHV-8
      seroprevalence was 6% among MSM and 5% among men who have sex only with women
      (MSW). In multivariate analysis, unprotected receptive anal sex during the past 6
      months, injection drug use, and cytomegalovirus infection were associated with
      HHV-8 seropositivity in MSM. CONCLUSION: The HHV-8 seroprevalence among these
      young MSM was similar to the HHV-8 seroprevalence among young MSW, but lower than
      seroprevalence estimates in earlier studies of older MSM. The association of MSM
      between HHV-8 infection and unprotected receptive anal sex supports previous
      findings that HHV-8 is sexually transmitted. Although CMV infection and injection
      drug use may be markers for unsafe sexual practices, it is also possible that
      these are independent risk factors for acquiring HHV-8.

PMID- 11289202
TI  - Pedal interdigital condylomata lata: a rare sign of secondary syphilis.
AB  - BACKGROUND: Condylomata lata of the toe webs are uncommon manifestations of
      secondary syphilis. Considering the recent decline in the incidence of syphilis
      in the United States, such lesions are likely to present infrequently. In some
      cases, this phenomenon may be the only physical sign of syphilis; therefore, it
      is important that a high index of suspicion is maintained when evaluating toe web
      lesions in patients at epidemiologic risk for syphilis. GOALS: A case of
      secondary syphilis presenting solely with interdigital condyloma lata in the toe
      web spaces is reported, and similar cases reported in the literature are
      reviewed. STUDY DESIGN: This article documents the diagnosis of secondary
      syphilis based on a positive serology in conjunction with the development of
      interdigital condyloma lata as the only physical finding suggestive of lues.
      RESULTS: The latter lesions resolved after appropriate, adequate antibiotic
      therapy. CONCLUSIONS: A case of condylomata lata of the toe webs without other
      pertinent physical findings is presented. Analogous to lesions typically seen in
      the anogenital region, moist exophytic toe web plaques may represent condyloma
      lata and thereby be a sign of secondary syphilis. The differential diagnosis
      includes tinea pedis, erythrasma, macerated corns, verrucae, and several tropical
      mycoses (chromomycosis, mycetoma).

PMID- 11289203
TI  - Immunohistochemistry of ultimobranchial thyroid carcinomas in seven slaughtered
      cows and one bull.
AB  - Eight thyroid gland epithelial tumors were found in 7 cows and 1 bull in a
      retrospective study of thyroid gland lesions in slaughtered cattle. All tumors
      were classified as ultimobranchial thyroid carcinomas based on morphology and
      immunohistochemistry. All tumors consisted of solid sheets and nests of polygonal
      to oval epithelial cells, with more sparsely dispersed colloid-filled follicles.
      Connective tissue separating nests of epithelial cells varied from delicate
      fibrovascular stroma to dense collagenous stroma. Fusiform epithelial cells with
      rare neural fibers and ganglion cells were present in 1 tumor. Cells within solid
      areas of these tumors were immunoreactive for calcitonin, calcitonin gene-related
      peptide, neuron-specific enolase, and synaptophysin. Colloid and follicle cells
      were immunoreactive for thyroglobulin. Few follicle cells also were reactive for
      calcitonin gene-related peptide. Neoplastic cells invaded the fibrous capsules in
      all 8 cattle. These tumors represented proliferation of a mixed population of
      undifferentiated cells, C cells, and thyroid follicular epithelial cells,
      presumably derived from the thyroid ultimobranchial bodies. These ultimobranchial
      carcinomas in slaughtered cattle are comparable to ultimobranchial tumors
      described in dairy bulls and the intermediate type of thyroid gland carcinomas
      (mixed thyroid medullary carcinomas) described in human beings.

PMID- 11289204
TI  - Evaluation of canine serum thyrotropin (TSH) concentration: comparison of three
      analytical procedures.
AB  - A comparative study of 3 analytical methods (immunoradiometric assay, enzyme
      immunometric assay, and chemiluminescent immunometric assay) for canine serum
      thyrotropin (TSH) was performed. Ninety-six dogs were included in the study. The
      within- and between-run precision was evaluated for each method, and correlations
      for the results obtained with each method were examined. The best within- and
      between-run precision was obtained with the chemiluminescent immunometric assay.
      Satisfactory correlations for the 3 analytical procedures were obtained but
      varied in relation to serum TSH concentration.

PMID- 11289205
TI  - A one-tube nested polymerase chain reaction for the detection of mycobacterium
      bovis in spiked milk samples: an evaluation of concentration and lytic
      techniques.
AB  - The objective of this study was to evaluate the use of a one-tube nested
      polymerase chain reaction (OTN PCR) with 5 concentration and lytic treatments for
      the detection of Mycobacterium bovis in experimentally inoculated milk samples
      (spiked samples). OTN PCR and the following treatments were tested in inoculated
      samples: 1) centrifugation; 2) C18-carboxypropylbetaine + capture resin 1 +
      Proteinase K (CB18-CH-PK); 3) centrifugation + capture resin 1 + Proteinase K; 4)
      centrifugation + capture resin 2 + Proteinase K; and 5) centrifugation +
      immunomagnetic separation (IMS). The OTN PCR and the 5 treatments were evaluated
      in 2 different sets of spiked milk samples. One set consisted of 10-fold serial
      dilutions of a phenol-killed M. bovis in milk to final concentrations ranging
      from 5 to 50,000 cells/ml of milk. The other set of samples consisted of 2.5
      serial dilutions of milk spiked with M. bovis to final concentrations ranging
      from 20.5 to 5,000 cells/ml of milk. Each treatment was repeated 5 times at each
      cell concentration. CB18-CH-PK and IMS were significantly more sensitive than
      other treatments. The lowest detection limit for these techniques was 20-50
      cells/ ml of spiked milk. The specificity of OTN PCR in this study was high as
      demonstrated by the lack of DNA amplification products when M. bovis cells were
      not present in the samples. [The OTN PCR used in conjunction with CB18-CH-PK or
      IMS could be effectively used as a diagnostic and/or screening test for the
      detection of M. bovis in milk from herds with bovine tuberculosis.]

PMID- 11289206
TI  - Comparison of purified protein derivatives and effect of skin testing on results
      of a commercial gamma interferon assay for diagnosis of tuberculosis in cattle.
AB  - Purified protein derivatives (PPD) prepared in the USA were compared with those
      prepared in Australia by a private company (CSL Veterinary) for use with a
      commercial gamma interferon (gamma-IFN) assay for diagnosis of bovine
      tuberculosis. The effect of skin testing on results of the gamma-IFN assay was
      determined, and results were compared when blood samples were stimulated with PPD
      within 2 hours and after 24 hours of sample collection. Twenty cattle that were
      sensitized by subcutaneous injection of heat-killed Mycobacterium bovis were
      randomly divided into 3 groups. Cattle in group A were tested with the caudal
      fold skin test (CFT) on day 0 and the comparative cervical skin test (CCT) on day
      7. Cattle in group B were tested with the CFT on day 0 and the CCT on day 63, and
      group C cattle were not skin tested. Blood samples for the gamma-IFN assay were
      collected at various times throughout the study period. Optical density (OD)
      values for the gamma-IFN assay were not significantly different when blood
      samples were stimulated with US avian PPD and CSL avian PPD. However, OD values
      were significantly higher for US bovine PPD than for CSL bovine PPD. However, the
      final interpretation of the gamma-IFN assay was usually the same when using
      either US or CSL PPD. In addition, OD values for the gamma-IFN assay were
      significantly higher for blood samples collected after sensitized cattle were
      skin tested than for samples collected from the same cattle before skin testing
      or from cattle not skin tested. The OD values for blood samples stimulated within
      2 hours of sample collection were significantly higher than for samples
      stimulated 24 hours after sample collection. However, OD values for all PPD
      stimulated samples from sensitized cattle were significantly higher in samples
      collected 3 days after skin testing and stimulated 24 hours after collection than
      for samples from the same animals collected before skin testing and stimulated
      within 2 hours of sample collection. Results of this study indicate that PPD
      prepared in the USA or Australia can be used to stimulate blood samples for the
      gamma-IFN assay. Skin testing cattle prior to collection of blood for the gamma
      IFN assay boosts production of gamma-IFN by lymphocytes from cattle that have had
      prior exposure to M. bovis antigens. Use of the gamma-IFN assay in conjunction
      with skin testing may improve detection of cattle infected with M. bovis. In
      addition, the increase in production of gamma-IFN after skin testing will permit
      greater flexibility in conducting the assay because samples can be stimulated
      after they have been shipped overnight rather than only on the day of sample
      collection.

PMID- 11289207
TI  - Validation of synthetic peptide enzyme immunoassays in differentiating two
      subgroups of ruminant respiratory syncytial virus.
AB  - Subgroup-specific peptide-based enzyme immunoassays from each respective G
      glycoprotein of the ovine and the bovine respiratory syncytial virus (RSV) were
      developed to detect RSV-specific IgG responses in cattle. Antigenic peptides from
      the respective G-glycoprotein were identified from the extracellular central
      hydrophobic region (amino acids 158-189) located between 2 mucin-rich regions.
      These antigenic peptides identified by epitope mapping from each G-glycoprotein
      were synthesized and used to develop the subgroup-specific enzyme immunoassays.
      The negative cutoff for each enzyme immunoassay was established as the mean
      optical density of indirect immunofluorescent antibody-negative bovine sera plus
      3 SDs. The sensitivity (82.9%) and specificity (100%) of the bovine enzyme
      immunoassay and the specificity (95.8%) of the ovine enzyme immunoassay were
      determined by comparison with indirect immunofluorescence (used as the "gold
      standard"). The negative and positive predictive values were calculated for each
      assay. The presence of serum antibody to ovine RSV in cattle implies that this
      virus infects cattle and may contribute to the pathogenesis of bovine respiratory
      disease.

PMID- 11289208
TI  - Prevalence of ovine and bovine respiratory syncytial virus infections in cattle
      determined with a synthetic peptide-based immunoassay.
AB  - Subgroup-specific peptide-based enzyme-linked immunosorbent assays from the G
      protein of the ovine and bovine respiratory syncytial virus (RSV), respectively,
      were used to determine the prevalence of the ovine and bovine subgroup strains of
      RSV infections in cattle. A total of 1,102 bovine serum samples were obtained
      from 6 diagnostic laboratories located in the northwestern and the southeastern
      USA and were tested for antibody to either the bovine or ovine subgroups of RSV.
      Antibody to viruses from each subgroup was present in samples from each region
      and all states tested. The Southeast had a higher prevalence of the bovine
      subgroup strains (69.5%). Then did the Northwest (40.9%). The prevalence of the
      ovine strain was similar for the two regions (16.7% in the southeast, 14.9% in
      the northwest). The overall prevalence was 56.6% for the bovine strain and 15.9%
      for the ovine strain. These results suggest members of the ovine subgroup of RSV
      circulate in the cattle population but with less frequency than those viruses of
      the bovine subgroup.

PMID- 11289209
TI  - Detection and duration of porcine reproductive and respiratory syndrome virus in
      semen, serum, peripheral blood mononuclear cells, and tissues from Yorkshire,
      Hampshire, and Landrace boars.
AB  - Because transmission of porcine reproductive and respiratory syndrome virus
      (PRRSV) can occur through boar semen, it is important to identify persistently
      infected boars. However, even for boars given the same PRRSV strain and dose,
      variability in the duration of viral shedding in semen has been observed,
      suggesting that host factors are involved in PRRSV persistence. To determine
      whether there are host genetic factors, particularly litter and breed differences
      related to the persistence of PRRSV, 3 litters from 3 purebred swine breeds were
      used for this study. It was also determined whether PRRSV could be detected for a
      longer period of time in serum, semen, or peripheral blood mononuclear cells
      (PBMC) and if PRRSV could still be detected in tissues after these antemortem
      specimens were PRRSV negative for a minimum of 2-3 weeks. Three Hampshire, 3
      Yorkshire, and 2 Landrace PRRSV-naive boars were obtained and inoculated
      intranasally with a wild-type PRRSV isolate (SD-23983). All boars within each
      breed were from the same litter, and litters were within 9 days of age. Serum and
      PBMC were collected twice weekly from each boar and analyzed for the presence of
      PRRSV by virus isolation and the polymerase chain reaction (PCR). Serum was also
      used to obtain virus neutralization titers and enzyme-linked immunosorbent assay
      S/P values. Semen was collected twice weekly from 7 of 8 boars and analyzed by
      PCR. After all specimens were PRRSV negative for a minimum of 2-3 weeks, each
      boar was euthanized, and 21 tissues plus saliva, serum, feces, and urine were
      collected. All postmortem specimens were evaluated by virus isolation. Specimens
      that were PRRSV negative by virus isolation were then evaluated by PCR. The mean
      number of days (+/-SD) for the duration of PRRSV shedding in semen was 51+/-26.9
      days, 7.5+/-4.9 days, and 28.3+/-17.5 days for Landrace, Yorkshire, and Hampshire
      boars, respectively. Because of small sample sizes and large SDs, the differences
      in duration of PRRSV shedding in semen between breeds were not considered
      significant. However, the trend suggested that Yorkshire boars were more
      resistant to PRRSV shedding in semen than were Landrace boars, requiring further
      investigation using a larger numbers of boars. PRRSV was detected for a longer
      period in semen than in serum or PBMC in 4 of 7 boars. Viremia could be detected
      for a longer period in serum than in PBMC in 6 of 8 boars. After a minimum of 2-3
      weeks of PRRSV-negative serum, semen, and PBMC, PRRSV could still be detected in
      the tonsil of 3 of 8 boars by virus isolation, indicating that boars still harbor
      PRRSV within the tonsil even though antemortem specimens are PRRSV negative.

PMID- 11289210
TI  - Paramyxovirus infection in caiman lizards (Draecena guianensis).
AB  - Three separate epidemics occurred in caiman lizards (Dracaena guianensis) that
      were imported into the USA from Peru in late 1998 and early 1999. Histologic
      evaluation of tissues from necropsied lizards demonstrated a proliferative
      pneumonia. Electron microscopic examination of lung tissue revealed a virus that
      was consistent with members of the family Paramyxoviridae. Using a rabbit
      polyclonal antibody against an isolate of ophidian (snake) paramyxovirus, an
      immunoperoxidase staining technique demonstrated immunoreactivity within
      pulmonary epithelial cells of 1 lizard. Homogenates of lung, brain, liver, or
      kidney from affected lizards were placed in flasks containing monolayers of
      either terrapene heart cells or viper heart cells. Five to 10 days later,
      syncytial cells formed. When Vero cells were inoculated with supernatant of
      infected terrapene heart cells, similar syncytial cells developed. Electron
      microscopic evaluation of infected terrapene heart cells revealed
      intracytoplasmic inclusions consisting of nucleocapsid strands. Using negative
      staining electron microscopy, abundant filamentous nucleocapsid material with a
      herringbone structure typical of the Paramyxoviridae was observed in culture
      medium of infected viper heart cells. Seven months following the initial
      epizootic, blood samples were collected from surviving group 1 lizards, and a
      hemagglutination inhibition assay was performed to determine presence of specific
      antibody against the caiman lizard isolate. Of the 17 lizards sampled, 7 had
      titers of < or =1:20 and 10 had titers of >1:20 and < or =1:80. This report is
      only the second of a paramyxovirus identified in a lizard and is the first to
      snow the relationship between histologic and ultrastructural findings and virus
      isolation.

PMID- 11289211
TI  - Diagnosis of preclinical and subclinical scrapie in a naturally infected sheep
      flock utilizing currently available postmortem diagnostic techniques.
AB  - Scrapie is a naturally occurring transmissible encephalopathy of sheep and goats.
      Currently available methods for diagnosis are the presence of characteristic
      histopathologic changes and detection of an abnormal form of prion protein
      (PrPres) in the brains of affected animals. This study documents preclinical and
      subclinical scrapie in a flock of 16 sheep utilizing histopathology,
      immunohistochemistry (IHC), western blot, and electron microscopy (for scrapie
      associated fibrils) for confirmation of the disease. Prior to necropsy, none of
      the sheep showed signs of clinical scrapie. Based on the results of
      histopathology and positive PrPres tests, 3 ewes were found to have subclinical
      scrapie. An additional ewe, which did not have histopathologic changes in the
      brain but was positive by IHC and western blot,was considered a preclinical case
      of scrapie. None of the sheep had amyloid in the brain stem.

PMID- 11289212
TI  - An atypical lymphoma of T-cell lineage in the thorax of an aged cow.
AB  - An aged beef cow was presented for signs of thoracic disease. A complete clinical
      and diagnostic workup suggested neoplasia. Postmortem examination revealed a
      lymphoma of T-cell lineage confined solely to the thoracic cavity, predominantly
      in lung tissue. The diagnosis was based on light and electron microscopy,
      immunohistochemistry, and negative bovine leukemia virus and bovine
      immunodeficiency virus results.

PMID- 11289213
TI  - Orbital adenocarcinoma of lacrimal gland origin in a dog.
AB  - A 13-year-old intact female mixed-breed dog was presented for a progressive
      enlargement of the right eye, which had been treated previously for
      conjunctivitis. A round, firm mass, approximately 4 cm in diameter, was
      protruding from the superotemporal aspect of the right orbit, displacing the
      eyeball anteriorly and ventromedially. The mass was encapsulated, distinct from
      the eyeball, and not associated with the eyelids. On cut surface, there was a
      pale multilobulated periphery, with a dark red, soft, and depressed core.
      Histologically, tumor cells formed cords and tubules, which were stained with
      mouse anti-human cytokeratin antibody AE1/AE3. Residual glands were serous, and
      the majority of tumor cells were negative for mucin. The supraorbital location,
      encapsulation, and residual serous glands suggest that this mass was a low-grade
      adenocarcinoma of the lacrimal gland.

PMID- 11289214
TI  - Isolation of genomic DNA from feathers.
AB  - The use of feathers in veterinary clinical practice simplifies the sampling of
      avian genomic DNA, especially when blood extraction is difficult because of the
      age or the size of the bird. A rapid and accurate protocol was used to isolate
      high-quality genomic DNA from feathers. The technique includes a lysis step of
      the feather quill, which differs in temperature and time of incubation depending
      on the feather size. Purification of genomic DNA is performed with phenol:
      chloroform: isoamyl alcohol extraction and ethanol precipitation. This protocol
      consistently provided significant amounts of high-quality genomic DNA from more
      than 800 birds belonging to 120 different species. Genomic DNA isolated with this
      method was used for Southern blotting and also in several polymerase chain
      reaction systems devoted to sex determination and paternity testing.

PMID- 11289215
TI  - Comparison of two enzyme-linked immunosorbent assays for serologic diagnosis of
      paratuberculosis (Johne's disease) in cattle using different subspecies strains
      of Mycobacterium avium.
AB  - Serologic diagnosis of bovine paratuberculosis (Johne's disease) with currently
      available tests may give false-positive results due to cross-reactions with avian
      and bovine tuberculosis viruses and other infectious agents. Indirect enzyme
      linked immunosorbent assays (ELISA) for detection of antibodies against
      paratuberculosis based on antigens from Mycobacterium avium subsp. avium (A
      ELISA) and M. avium subsp. paratuberculosis (P-ELISA) were compared. Despite an
      expected higher specificity for M. a. paratuberculosis in the P-ELISA, the 2
      antigens were equally suitable for demonstration of antibody to M. a.
      paratuberculosis in cattle. Receiver operating characteristic (ROC) curves was
      used to demonstrate the possible antigenic relationship. The area under the curve
      (AUC) was calculated for each of the 2 ROC curves. The AUC for the P-ELISA ROC
      curve was 0.9197, and the AUC for the A-ELISA ROC curve was 0.9149, demonstrating
      a negligible difference in efficiency of the 2 tests (z = 0.182).

PMID- 11289216
TI  - Unilateral concurrence of pyelocaliceal diverticula and intracapsular
      angiomyolipoma in the kidney of a cat.
AB  - A 7-month-old cat was examined for progressive abdominal distension. Radiography
      showed a fluid-containing cyst, which had subsequently ruptured as the result of
      a fall. Nephrectomy was performed, and examination revealed the coexistence of
      pyelocaliceal diverticula with a cystic intracapsular angiomyolipoma (mesenchymal
      hamartoma) in the left kidney. The diverticula were present on both cranial and
      caudal poles of the kidney and were lined by transitional epithelium. The
      hamartoma was characterized by the presence of multiple mesenchymal tissues,
      including thick-walled blood vessels, smooth muscle, and adipose tissue.

PMID- 11289217
TI  - Experimentally induced cholangiohepatopathy by dosing sheep with fractionated
      extracts from Brachiaria decumbens.
AB  - Cholangiohepatopathy was induced in 5 lambs by oral administration of extracts
      from signal grass (Brachiaria decumbens) in Brazil. Grossly there were pale foci
      multifocally distributed throughout the hepatic parenchyma in 4 lambs. The
      microscopic changes, which were similar to those produced by other steroidal
      sapogenins-containing plants such as Tribulus terrestris and Panicum spp.,
      included multifocal cholangitis, bile duct proliferation, and the presence of
      crystals in the biliary system.

PMID- 11289218
TI  - Rare detection of Neospora caninum in placentas from seropositive dams giving
      birth to full-term calves.
AB  - Neospora caninum is thought to be transmitted to cattle by dogs, the only known
      definitive host. Although aborted fetuses seem the most likely source of
      infective material for dogs, placentas from seropositive dams appear also as a
      potential source of infective material. The objective of the study was to
      evaluate the presence of N. caninum organisms in placentas of full-term calves
      born to seropositive cows. Sixteen placentas, 11 from Neospora-seropositive cows,
      were examined histologically and by immunohistochemistry and polymerase chain
      reaction (PCR) assay for the presence of N. caninum. Mild placentitis was
      observed in all placentas. Neospora caninum was not identified by
      immunohistochemistry, but placentas from 2 seropositive dams were positive for N.
      caninum by PCR. These results suggest that placentas of full-term calves from
      seropositive cows may be a potential source of N. caninum for dogs, but the
      incidence of this mode of transmission is likely to be low.

PMID- 11289219
TI  - Genotypic prevalence of apx1V in Actinobacillus pleuropneumoniae field isolates.
AB  - A total of 90 Actinobacillus pleuropneumoniae field strains from pigs were
      serotyped by slide agglutination and analyzed for the presence of the apxIV gene
      by polymerase chain reaction. Of the 90 isolates serotyped, serotypes 2 (47
      isolates) and 5 (25 isolates) were the most common, followed by serotype 6 (10
      isolates). Three isolates belonged to serotype 7, and 5 isolates could not be
      typed. All 90 A. pleuropneumoniae field isolates tested carried the apxIV gene.
      This gene is species specific rather than serotype specific. Therefore, the ApxIV
      toxin has potential value for use both in vaccines and in diagnostic tests.

PMID- 11289220
TI  - Effect of dietary factors on the detection of fecal occult blood in cats.
AB  - Eight different diets were each fed to 6 cats to evaluate the effect on a guaiac
      and an o-tolidine fecal occult blood test. Fecal samples were collected from day
      5 through day 7. Canine blood or pure cottage cheese were used as positive and
      negative controls, respectively. One hundred thirty-four fecal samples were
      analyzed. The dry fish (capelin) and vegetable (tapioca) diet and the pure
      cottage cheese diet had only negative results in both tests, whereas a canned
      chicken and cereal (rice) diet had negative results in all fecal samples in the o
      tolidine tablet test and in 10 of 16 fecal samples in the guaiac paper test. All
      other fecal samples from cats eating 6 other diets and the canine blood additive
      were positive in both fecal occult blood tests. These results indicate that
      occult blood tests based on o-tolidine and guaiac are clinically useful, but cats
      need to be on a strict diet before the tests are used.

PMID- 11289221
TI  - Pharmacokinetics study of a novel chimeric single-chain variable fragment
      antibody against western equine encephalitis virus.
AB  - A novel recombinant single-chain fragment variable (scFv) antibody against
      western equine encephalitis (WEE) virus has been previously constructed and
      partially characterized. The RS10B5huFc antibody was made by fusing an anti-WEE
      scFv to a human heavy-chain IgG1 constant region. The RS10B5huFc antibody was
      functional in binding to WEE virus in enzyme-linked immunosorbent assays
      (ELISAs), and the Fc domain of the antibody was capable of effector functions,
      such as binding to protein G and human complement. In this study, the RS10B5huFc
      antibody was further characterized by BIAcore analyses and was found to possess a
      binding affinity to a WEE virus epitope (K[D] = 9.14 x 10(-6) M), 4.5-fold lower
      than its parental mouse monoclonal antibody (MAb) 10B5 E7E2 (K[D] = 2 x 10(-6)
      M). No cross-reactivity was found between the RS10B5huFc antibody and three other
      alphaviruses (Sindbis virus [SIN], Venezuelan equine encephalitis [VEE] virus,
      and eastern equine encephalitis [EEE] virus). Pharmacokinetics studies showed
      that the RS10B5huFc antibody (free and encapsulated) was found to be retained in
      the lungs of mice for greater than 48 h when administered intranasally. In
      contrast, when administered intramuscularly to mice, the RS10B5huFc antibody was
      not detected in the lungs and only found in the liver and kidneys.

PMID- 11289222
TI  - Immune response to progesterone immobilized on Cu2+-induced amphifilic
      polyelectrolyte-protein complex: antigen specificity and affinity of hybridoma
      clones.
AB  - Cu2+-mediated complex formation between copolymers of acrylic acid with N
      isopropyl-acyrlamide (CP1) and negatively charged covalent conjugate of bovine
      serum albumin with progesterone (BSA.P) was studied in neutral water in the
      presence of Cu2+. It was shown that under conditions where CP and BSA.P are
      negatively charged and incapable of binding to one another, the divalent Cu2+ act
      as "fasteners" promoting the formation of relatively stable water-soluble ternary
      polycomplexes. The immunogenic properties of ternary mixtures BSA.P-Cu2+-CP1 and
      BSA.P+IFA were investigated and the production of monoclonal antibodies (MAbs)
      against progesterone hormone was analyzed. Fusion following the two different
      immunization procedures resulted in the growth of comparable numbers of
      progesterone-specific MAbs with apparently similar antigen affinities. Thus,
      immunizations using antigens in BSA.P-Cu2+-CP1 appear to provide an efficient
      alternative to incomplete Freund's adjuvant.

PMID- 11289224
TI  - A monoclonal antibody specific for human thymidine kinase 1.
AB  - Previous research has shown that thymidine kinase 1 (TK1), a nucleotide salvage
      pathway enzyme, is an accurate prognostic and diagnostic tumor marker. However,
      the current radioisotope assay for TK1 is cumbersome and has hampered the
      clinical application of this diagnostic technique in cancer management. To
      overcome the problems of the current radioisotope assay, we have produced
      monoclonal antibodies (MAbs) using purified TK1 from Raji cell extract.
      Production and confirmation of their specificity was confirmed using Western
      blot, immunohistochemical staining, TK1 activity inhibition assays, and enzyme
      linked immunoadsorbent assay (ELISA) techniques. Thus, in the future, these
      antibodies may aid in the early detection of cancer and more accurate prognosis,
      as well as allowing for an increased ability to study the function of TK1 in
      basic cellular processes.

PMID- 11289223
TI  - Detection of pET-vector encoded, recombinant S-tagged proteins using the
      monoclonal antibody ATOM-2.
AB  - The 15-meric S-tag is a truncated form of the S-peptide, which builds together
      with the 103 amino acid large S-protein the whole ribonuclease S-protein. Its
      small size and excessive solubility have made the S-tag an excellent fusion
      partner in the production of recombinant proteins, and a large variety of
      applications have been reported using the S-tag as a carrier. While S-tagged
      proteins were mostly detected and analyzed so far by use of their affinity to S
      proteins, monoclonal antibodies (MAbs) for this tag have been not available. The
      generation of antibodies specific for S-tagged proteins is expected to broaden
      the range of applications of such S-tag fused recombinant proteins, and in this
      context, a novel MAb termed ATOM-2 was generated that specifically binds S-tagged
      proteins, which have been expressed using pET-vectors. Antigen specificity of
      ATOM-2 was confirmed in Western blot and enzyme-linked immunoadsorbent assay
      analysis, and using a series of amino acid deletion mutants, the binding epitope
      of ATOM-2 was precisely mapped. This showed that ATOM-2 recognizes the C-terminal
      part of the 15-meric S-tag in context with a few residues of vector encoded
      sequences. The core sequence for ATOM-2 binding epitope is "His-Met-Asp-Ser-Pro
      Asp-Leu-Gly-Thr," which is present in all pET-expression vectors encoding S-tag
      fusion proteins. Because the ATOM-2 binding region does not overlap with the S
      protein binding sequence, a convenient tool is provided for the simultaneous or
      alternative detection, purification, and analysis of recombinant S-tagged
      proteins to conventional S-proteins.

PMID- 11289225
TI  - Development of a monoclonal antibody specific to a recombinant envelope protein
      from dengue virus type 4 expressed in Pichia pastoris.
AB  - A mouse monoclonal antibody (MAb, 4B6) was able to recognize dengue virus type 4
      envelope (E) protein both as a recombinant protein in Pichia pastoris and when it
      was present in infected brains of suckling mice. 4B6 was characterized by enzyme
      linked immunoadsorbent assay (ELISA), hemaglutination inhibition, neutralization,
      and immunoblot. The MAb was isotyped as IgG2a. It was serotype 4 specific and it
      inhibited hemaglutination and neutralized homologous virus. It did not enhance
      infection of P338D1 cells by dengue type 4 virus strain H-241 strain. This MAb
      was reactive with recombinant E protein and dengue 4 virus, as revealed by
      Western blot. In vivo, MAb 4B6 conferred passive protection in mice challenged
      with homologous virus. Currently, this MAb is being used to purify recombinant E
      protein for further studies.

PMID- 11289226
TI  - Production of monoclonal antibodies against mammalian Ring1B proteins.
AB  - The Polycomb group (PcG) genes play a role of transcriptional repressor for long
      term maintenance of the Hox cluster gene expression. Recently two structurally
      similar gene products, Ring1A and Ring1B, were identified. Genetic evidence has
      indicated that Ring1A has Pc-G properties, however, Ring1B functions are still
      unknown. To gain functional insights for Ring1B, we raised the mouse monoclonal
      antibodies (MAbs) against murine Ring1B protein. Using these antibodies, we have
      detected specifically mouse, human and monkey Ring1B gene products from whole
      cell extracts in immunoblot and immunoprecipitation analyses. Immunofluorescent
      staining by the antibodies has shown that endogenous Ring1B proteins clearly co
      localize with Ring1A at the pattern of diffuse nuclear speckles. Together with
      their sequence similarity, Ring1B also may function as a Pc-G protein. Finally,
      we have proposed that the anti-Ring1B would be useful for biochemical and
      cytological analyses of Ring1B and Pc-G complex.

PMID- 11289227
TI  - Establishment of hybridoma cell lines producing monoclonal antibodies against
      hepatitis B virus surface antigens (a, d, and r) and development of sensitive
      ELISA diagnostic test.
AB  - A new treble-coated enzyme-linked immunoadsorbent assay (ELISA) kit of detecting
      Hepatitis B virus (HBV) surface antigen subtypes a, d and r (HBsAg-a, -d, -r) was
      developed by using four established hybridoma cell lines, of which two
      specifically secrete monoclonal antibodies (MAbs) against HBsAg-a (anti-HBsAg-a),
      one against -d (anti-HBsAg-d), and one against -r (anti-HBsAg-r). The approach of
      hybridoma cell lines' establishment were by fusing myeloma cells (SP2/0) with
      splenocytes from BALB/c mice immunized with a mixture of HBsAg-a, -d, -r. The
      ascitic MAb productivity of the four cell lines was at the titres of 1:10(6)
      1:10(8). A treble-coated ELISA based HBV diagnostic kit was developed for
      detecting all of the three responding subtypes of HBsAgs. A 96-well ELISA
      microplate was coated with anti-HBSAg-a, -d, -r at a ratio of 3: 1: 0.5, with a
      horseradish peroxidase (HRP) conjugated anti-HBsAg-a as the labelled antibody.
      For clinical application, the new developed diagnostic kit detected HBsAgs of
      adr, adw, ayr, and ayw at a rate of lower than 0.25, 0.25, 0.5, and 0.5 ng/mL,
      respectively. Results indicated that this kit was more rapid and sensitive than
      that other current ELISA-based kits coated with a single MAb (e.g., anti-HBsAg
      a).

PMID- 11289228
TI  - Development of a sandwich ELISA test for arginase measurement based on monoclonal
      antibodies.
AB  - Human arginase was purified from liver and two monoclonal antibodies (MAbs), HA1
      and HA2, were produced by fusion of spleen cells from an arginase-immunized
      BALB/c mouse and the NS-1 myeloma cell line. Both MAbs were of the IgG3 subclass
      and contained the kappa light chain. HA1 inhibited arginase activity, suggesting
      that it binds to the arginase catalytic site. HA1 and a horseradish peroxidase
      conjugated polyclonal rabbit anti-human arginase antibody were used to develop a
      sandwich enzyme-linked immunoadsorbent assay (ELISA) for the quantification of
      human arginase, which can be used in the 1 to 300 ng/mL range. Because of its
      sensitivity and specificity, this MAb can be successfully applied to the ELISA
      quantification of arginase in serum and culture supernatants.

PMID- 11289229
TI  - Monoclonal and polyclonal antibodies against human ferritin, a nonspecific tumor
      marker.
AB  - The aim of this study was to produce monoclonal and polyclonal antibodies against
      a nonspecific tumor marker, human ferritin. Hyperimmune ICR mice produced
      polyclonal antibodies after injection with 0.5 mL pristane, and were injected
      with NS-1 myeloma cells 2 weeks later. Hyperimmune Balb/c mice were used for the
      production of monoclonal antibodies (MAbs). Mice were immunized four times, given
      a final boost, and their spleen cells were collected and fused with NS-1 myeloma
      cells under the presence of PEG 1500. The fused cells were then selected in the
      HAT-RPMIX medium. Anti-ferritin antibody-secreting hybridoma cell lines with high
      titer were cloned by enzyme-linked immunoadsorbent assay (ELISA) and then
      subcloned by limiting dilution in 15% fetal bovine serum (FBS) HT-RPMIX medium.
      Five murine hybridoma-producing antiferritin MAbs were obtained and designated
      1AD11F9, 1AD11E11, 2AD11D2, 2AD11A5, and 3AD11G8. Isotypes of these MAbs were
      identified as IgM heavy chain and kappa light chain. Hitrap Protein A and Hitrap
      IgM purification column were used for the purification of polyclonal and
      monoclonal antibodies, respectively.

PMID- 11289230
TI  - Self-reports of stress in Asian immigrants: effects of ethnicity and
      acculturation.
AB  - INTRODUCTION: Although the concept of stress is hard to define or measure, it is
      a phenomenon associated with a number of health conditions, including
      hypertension, heart disease, and decreased immunocompetency. Events such as
      migration are known to create stress; researchers refer to this as acculturative
      stress. Given that cultural background might influence a patient's recognition,
      interpretation, and coping mechanisms for stress, we wondered how self-reports of
      stress by Asian immigrants compare with those of non-Hispanic Whites, and how
      these self-reports vary with years since immigration, a proxy for acculturation.
      METHODS: Data from the National Health Information Survey for 1993 and 1995 were
      analyzed for six groups of Asian national origin, and were compared with non
      Hispanic Whites. Using ordered logistic regression, we examined self-reports of
      stress over two weeks and twelve months, as well as the changes in these self
      reports with years since immigration. RESULTS: Adjusted for age, income,
      educational level, marital status, and gender, Asian immigrants were uniformly
      less likely to report stress over a two-week period than were non-Hispanic Whites
      (OR ranges: 0.34[Asian Indian]-0.59[Korean], P values<.05). There were no
      significant differences in reported stress among Asian ethnic groups. Compared
      with immigrants who have lived in the United States for at least 15 years, recent
      immigrants (<1 year) were likely to report less stress over two weeks and twelve
      months, OR = 0.13 and 0.23, respectively, P values<.005. CONCLUSIONS: Despite
      their status as immigrants, Asians report less stress than non-Hispanic Whites.
      These reports of stress increase as years since immigration increase. One
      potential explanation for these discrepancies is under-reporting, which might
      reflect underlying cultural differences in the perception or definition of
      stress, differences that may diminish with "acculturation."

PMID- 11289231
TI  - Use of alternative medicines in a multi-ethnic population.
AB  - BACKGROUND: The prevalence and cost of regular use of non-prescribed alternative
      medicines are rising around the world, yet, little evidence is available that
      demonstrates the safety, efficacy, or effectiveness of specific alternative
      medicine interventions. It is of interest to understand how and why these
      practices have become so popular in different societies with different health
      care organizations and provisions, and which factors predict the regular use of
      alternative medicines. METHODS: We assessed the prevalence and the predictors of
      regular use of non-prescribed vitamin supplements, cod liver oil, primrose oil,
      and garlic in a cross-sectional population-based study in South London of 1,577
      men and women, aged 40-59 years (883 women, 523 White, 549 of African origin and
      505 of South Asian origin), when allowing for potential confounders. RESULTS: The
      prevalence of regular users of alternative medicines was 10.4% (164/1,577); 7.4%
      (116) made regular use of non-prescribed vitamin supplements, whereas 5.3% (84)
      used either cod liver oil, primrose oil, or garlic preparations. When adjusted
      for age, ethnicity and social class, women were more likely than men to use at
      least one alternative medicine (OR 2.09 [95% CI 1.45-3.00]). This was true both
      for vitamin supplements (1.98 [1.29-3.03]) and for oil or garlic supplements
      (1.91 [1.17-3.14]). The use of oil or garlic (P<.005) but not vitamin supplements
      (P=.32) varied by ethnic group. In particular, Black people of African origin
      were more likely to use alternative medicines than either Whites (1.78 [1.07
      2.94]) or South Asians (1.66 [1.07-2.59]), the least common users. People in
      social classes IV and V were less likely to use alternative medicines (0.53 [0.31
      0.90]) than those in social classes I and II, though this was due more to lesser
      use of non-prescribed vitamin supplements than of cod liver oil, primrose oil or
      garlic. These associations were not attenuated by further adjustment for body
      mass index, smoking, marital status and age at leaving full-time education.
      CONCLUSIONS: The regular users of alternative medicines in London are more likely
      to be women, of African origin, and of higher socioeconomic status. Given the
      lack of evidence of efficacy and safety of these alternative medicines, it is
      important to understand the cultural differences in values and beliefs about
      traditional medicine that may underlie these findings.

PMID- 11289232
TI  - Differential response to targeted recruitment strategies to fitness promotion
      research by African-American women of varying body mass index.
AB  - OBJECTIVE: To assess patterns of recruitment into a community-based NCI-funded
      physical activity and dietary lifestyle change program targeting African-American
      women. DESIGN: Acquisition of a convenience sample to be screened for
      participation in a randomized, controlled prevention intervention. SETTING:
      African-American-owned and -operated health club located in an area of Los
      Angeles in which African Americans are concentrated. PARTICIPANTS: 893 African
      American women. RECRUITMENT STRATEGIES: Social networking/word-of-mouth, staff
      presentations, mass and targeted media, and physician referral. MAIN OUTCOME
      MEASURE: Completion of screening questionnaire indicating a desire to enroll in
      the study. Screening questionnaire domains included self-reported height and
      weight, recent participation in organized weight loss programs, ability to walk
      one mile unassisted, current medication use, smoking status, personal medical
      history of cancer, sociodemographic variables, and recruitment source. RESULTS:
      Sociodemographic and anthropometric characteristics distinguished between
      respondents obtained through different recruitment strategies. In particular,
      women with a higher body mass index (BMI) were more likely than those with lower
      BMIs (P = .014) to be recruited through more personalized methods (eg, social
      networking). CONCLUSIONS: Culturally tailored recruitment strategies are critical
      in securing the participation of members of "hard-to-reach" populations, who are
      both under-represented in health promotion research and at high risk for chronic
      diseases.

PMID- 11289233
TI  - Recruiting African Americans into research on cognitive aging.
AB  - A total of 218 adults with an average age of seventy-eight years participated in
      a study of memory performance in community elders. A computer-generated random
      zip code list of adults > or = 70 years of age was purchased and a four-phase
      telephone-screening plan was adopted. During the second year, the sampling plan
      had to be changed, with a convenience-sampling plan being adopted to recruit
      adequate numbers of African-American subjects. Fifty-seven percent of the African
      American subjects (N = 55) and 68% of the White subjects (N = 83) were recruited
      from random sampling methods. As compared to the random sample, the convenience
      sample was significantly older (80 vs 76), had more depression (12 vs 9), had
      lower physical functioning (46 vs 65), and less vitality (48 vs 60). On meta
      memory, the convenience sample scored higher than the random sample on
      achievement (3.84 vs 3.69), and lower on task (3.75 vs 3.85). The convenience
      sample scored significantly lower than the random sample on memory performance
      (15 vs 18), and memory self-efficacy (26 vs 33). More research is needed to
      document normative measures for cognitive function and to facilitate accurate
      comparisons between African-American elderly and other elderly.

PMID- 11289234
TI  - Historical assessment of nutrition studies using only African-American study
      subjects: gender, socioeconomic status, and geographic location.
AB  - While the African-American community has disproportionate rates of morbidity and
      mortality from chronic diet-related diseases, few studies have examined
      demographically the spectrum of these outcomes in the population. The purpose of
      this study is to determine the extent to which published scientific literature
      has examined African-American samples with sufficient specificity to identify
      nutrition problems in subsets of the population. Age, gender, socioeconomic
      status, geographic location, and sample size are used to examine study questions.
      In addition, the United States Department of Agriculture (USDA) Continuing Survey
      of Food Intakes for Individuals (CSFII) 1994-1996 is used to illustrate how
      evaluating nutrient variables by demographic indicators provides insights into
      the heterogeneity of nutrient intake patterns among African Americans. Relative
      to the adequacy of scientific investigation into these issues, a review of twenty
      nine studies conducted from 1970 to the present demonstrates bias in gender,
      income, and sample size for African-Americans-only dietary research samples.
      Relative to identifying dietary patterns that do not meet US dietary guidelines,
      pervasive patterns that persist across income groups were found, indicating the
      need for nutrition education programs at all levels. Although there are science
      based diet information available, it does not seem to have reached the African
      American community in numbers sufficient to be reflected in dietary changes as
      reported by surveys. This research demonstrates the need for detailed studies
      highlighting these issues, as well as the production of culturally appropriate
      nutrition education materials and methods that will be effective in reaching this
      population.

PMID- 11289235
TI  - The alternative medicine boom: a risk for African Americans.

PMID- 11289236
TI  - The disproportionate burden of diabetes in African-American and Hispanic
      populations.

PMID- 11289237
TI  - TNF and Fas-induced apoptosis during negative selection in thymic nurse cells.
AB  - Apoptosis of thymocytes associated with thymic nurse cells (TNCs) has been well
      documented. TNCs selectively bind and internalize immature alphabeta TCRlo CD4+
      CD8+ thymocytes in vitro. A subset of the internalized population matures to the
      alphabeta TCRhi CD69hi stage of development while the fraction that remains
      within the cytoplasm dies through the process of apoptosis. Negative selection by
      thymic cortical epithelial cells has been reported, but little is known about the
      apoptotic pathway(s) employed to facilitate the death signal. Using the TNC line
      tsTNC-1 that was reported earlier to maintain the ability to internalize
      alphabeta TCRlo CD4+ CD8+ cells in vitro, we investigated the role of Fas and
      TNFalpha in TNC-induced apoptosis. Our initial studies revealed that tsTNC-1
      cells express both FasL and TNFalpha apoptosis of triple positive cells was shown
      to be reduced approximately 50% in co-cultures of tsTNC-1 cells and thymocytes in
      the presence of either anti-TNFalpha or Fas-Fc. When maximum effective
      concentrations of both TNFalpha, and Fas-Fc were added to these co-cultures,
      apoptotic death was further reduced to approximately 68%. These results suggest
      that both TNFalpha and Fas apoptotic pathways are active during thymocyte
      selection by TNCs.

PMID- 11289238
TI  - Breast cancer, socioeconomics, and aging in minority populations.

PMID- 11289239
TI  - The Transcendental Meditation program: reducing the risk of heart disease and
      mortality and improving quality of life in African Americans.

PMID- 11289240
TI  - Research opportunities at the National Institute of Arthritis and Musculoskeletal
      and Skin Disease (NIAMS).

PMID- 11289241
TI  - The past as prologue: generational integrity.

PMID- 11289242
TI  - Polyphenols, flavonoids, food constituents and oils attenuate neurodegenerative
      process.

PMID- 11289243
TI  - Ethnicity and psychopharmacology.

PMID- 11289244
TI  - Seniors identity barriers to health care.

PMID- 11289246
TI  - Agreement in race-ethnicity coding between a hospital discharge database and
      another database.
AB  - OBJECTIVE: This study assessed the agreement in coding of race and Hispanic
      ethnicity for the same patients in a hospital discharge database and another
      database. METHODS: Race-ethnicity coding was examined for 72,276 cancer patients
      discharged from Connecticut hospitals (1992-1997) who were linked with the
      statewide cancer registry that included information on birthplace (for 76% of
      patients) and surname (for all patients). Surnames in the cancer registry were
      also linked with a list of Spanish surnames, to improve ascertainment of
      ethnicity among patients of probable Hispanic origin. RESULTS: Kappa coefficients
      (kappa) indicated substantial agreement (beyond that expected by chance) for
      White (kappa = .74) and Black (kappa = .93) race, Hispanic ethnicity (kappa =
      .73) and non-Hispanic White race-ethnicity (kappa = .83) categories. Kappa was
      moderate (ie, .52) for the Asian-Pacific Islander race category. Only 42% of
      Asian-Pacific Islanders and 62% of Hispanics in the cancer registry were
      similarly coded in the discharge database. CONCLUSIONS: Although both databases
      are imperfect, the findings suggest that ascertainment of certain racial-ethnic
      groups in hospital discharge databases could be improved if birthplace and
      surname were available.

PMID- 11289245
TI  - Impact of arthritis on disability among older Mexican Americans.
AB  - OBJECTIVE: To estimate the impact of self-reported diagnosis of arthritis at
      baseline on the two year incidence of limitation in activities of daily living
      and instrumental activities of daily living in initially non-disabled Mexican
      American elderly. DESIGN: Longitudinal study. SETTING Southwestern United States
      (Texas, New Mexico, Colorado, Arizona and California). SUBJECTS: A probability
      sample of 2,167 non-institutionalized Mexican-American men and women, aged 65 or
      older. MEASURES: Having ever been told by a doctor that a subject had arthritis,
      Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL),
      depressive symptomatology, presence of chronic diseases (diabetes mellitus, heart
      attack, stroke, cancer), and body mass index (BMI). RESULTS: Among non-disabled
      persons at baseline, 11.2% of subjects with arthritis reported at least one ADL
      limitation after two years, compared to 6.9% of subjects without arthritis.
      Similarly, among non-disabled persons at baseline, 34.7% of subjects with
      arthritis reported at least one IADL limitation after two years, compared to
      27.0% of subjects without arthritis. In logistic regression analysis, depression,
      diabetes, and arthritis were found to be predictive of the development of ADL
      disability, controlling for sociodemographic variables. Depression was the only
      condition that significantly predicted IADL disability. CONCLUSIONS: Subjects
      with arthritis were more likely to develop ADL and IADL disability over a two
      year period than those without arthritis.

PMID- 11289247
TI  - Hypertensive African Americans with kidney disease should seek advice from doctor
      about blood pressure medication.

PMID- 11289248
TI  - Body composition in women with sickle cell disease.
AB  - INTRODUCTION: Adults with sickle cell disease (SCD) have increased morbidity and
      low perceived health status, similar to patients with other chronic conditions.
      These patients may be sedentary due to exercise intolerance, physical incapacity
      due to sickle cell-related complications or medical conservatism. Obesity is an
      indicator of low health status and overall well-being in the general population,
      and we hypothesize that adults with SCD will have a high total body fat (%BF).
      The purpose of this study was to assess body composition in women with SCD using
      dual-energy X-ray absorptiometry (DXA). METHODS: Baseline medical examination,
      laboratory assessments, and seven-day activity recall to estimate energy
      expenditure (EE) were obtained for 22 women with SCD. BMI was calculated and
      whole body DXA was performed [fat mass (FM), fat-free soft tissue (FFST), and
      bone mineral content (BMC)]. Descriptive statistics were obtained and
      associations between body composition indices, total hemoglobin (Hb), treatment
      with hydroxyurea (HU), and EE were determined. RESULTS: Patient age was 30.5+/
      9.3 years and total Hb was 8.85+/-1.92 g/dL (mean+/-SD). Mean body mass index
      (BMI) (22.6 kg/m2) was in the 'acceptable' range, while DXA measurement of mean %
      fat (32.6%) indicated obesity. Fat-free mass (FFM) was 40.0+/-5.62 and bone
      mineral density (BMD) was 1.13+/-0.14 g/cm2 (mean+/-SD). There were no
      correlations between body composition indices and total Hb, HU, or EE.
      CONCLUSIONS: This is the first report of high levels of adiposity, low FFM, and
      low BMD in normal weight women with SCD. The findings were not affected by total
      Hb, EE, HU. Further studies are needed to better define body composition, body
      composition determinants, and their impact on overall health status in adults
      with SCD.

PMID- 11289249
TI  - Association between smokeless tobacco use and breast cancer among Native-American
      women in North Carolina.
AB  - BACKGROUND: Cigarette smoking and smokeless tobacco use have been associated with
      the development of a variety of cancers. While cigarette smoking may be
      associated with breast cancer, smokeless tobacco use has never been evaluated as
      a breast cancer risk factor. This study explores such an association. METHODS: A
      complete census was carried out among Eastern Band Cherokee women aged 18 years
      and older, residing on tribal lands in western North Carolina. Self-reported
      alcohol, cigarette and smokeless tobacco use, demographic information, and
      personal history of breast cancer (stratified by age of onset < 55 years or > or
      = 55 years) were obtained by questionnaire. RESULTS: 1,070 out of 1,408 (76%)
      eligible women were interviewed. Current and former smokeless tobacco use was
      common (6% and 21%, respectively). Five cases of breast cancer were identified in
      women under the age of 55 years and 3 cases were found in women at > or = 55
      years. Only the odds ratio (OR) for younger-onset breast cancer among ever-users
      of smokeless tobacco was significantly elevated (OR = 7.79, 95% CI = 1.05-66.0).
      While the ORs for younger onset breast cancer were elevated among ever-smokers or
      women reporting at least monthly alcohol use, these were not significant (OR
      8.49, 95% CI = 0.09-200; and OR = 1.72, 95% CI = 0.19-15.2, respectively). No ORs
      were significantly elevated for breast cancer among older women. CONCLUSIONS:
      These preliminary data are the first to document an apparent relationship between
      smokeless tobacco use and breast cancer risk, but should be confirmed in other
      studies due to the small number of cases. The nearly 8-fold increase in risk
      suggests that smokeless tobacco is not a safe alternative to cigarette smoking.

PMID- 11289251
TI  - New recruitment model may improve health outcomes information.

PMID- 11289250
TI  - Determinants of mammographic densities among women of Asian, Native Hawaiian, and
      Caucasian ancestry.
AB  - This cross-sectional study explored the relation between mammographic densities
      (a predictor of breast cancer risk), ethnicity, and dietary factors among women
      in Hawaii. Thirty-nine postmenopausal women with Japanese, Chinese, Caucasian,
      and Native Hawaiian ancestry who had received a screening mammogram completed a
      medical, reproductive, and dietary history. Using a computerized method, we
      determined the total and the dense area of the breast and calculated the ratio
      between the two. Blood lipids were measured using standard methods. For
      statistical analysis, we applied analysis of variance and multiple linear
      regression. Whereas the mean dense area of the breast was one third smaller in
      Asian than in Caucasian and Native Hawaiian women, the percent of the breast
      occupied by dense tissue in the Asian women was slightly higher than in the
      Caucasian/Hawaiian group, possibly a result of the Asian women's smaller breast
      size. The exploratory analysis indicated inverse relations of body mass index,
      high-density lipoprotein cholesterol (HDLC), age at menarche, and soy intake with
      mammographic densities, as well as direct relations of estrogen use and family
      history with mammographic densities. The results of this study suggest that
      variations in these factors may be responsible for ethnic differences in
      mammographic densities and in breast cancer risk.

PMID- 11289252
TI  - Patterns of breast, cervical, colorectal, and prostate cancer in the Appalachian
      region of South Carolina.
AB  - OBJECTIVES: This study examined the relationship between demographic factors and
      other correlates of late stage diagnoses among residents in the Appalachian
      region of South Carolina. DESIGN: The study employed a cross-sectional study
      design. METHODS: Regional data from 4,928 prostate, breast, cervical, and
      colorectal cancer registry cases were examined as part of a statewide pilot
      registry effort. Frequencies and logistic regression procedures were performed to
      compute risk estimates for non-local stage of diagnosis across all four cancers,
      and for each of the four cancers by age and race. RESULTS: African Americans were
      1.6 times more likely than Whites to be diagnosed with a non-local stage of
      cancer. For breast and prostate cancer, those 65 and older were significantly
      more likely to receive non-local state stage of diagnosis than those under 50.
      For cervical cancer, the odds of receiving a non-local stage diagnosis declined
      with advancing age, with those over 65 being significantly less likely than those
      under 50 to receive non-local stage diagnoses. CONCLUSIONS: It is necessary to
      identify sub-populations experiencing high rates of non-local stage diagnoses of
      cancer to form the basis for the development of more effective cancer prevention
      and treatment programs.

PMID- 11289253
TI  - Socioeconomic status, ethnicity, and health care access among young and healthy
      women.
AB  - This study examined: (a) the relationship between socioeconomic status (SES) and
      health care access among healthy women; (b) which SES variable(s) were most
      strongly associated with HCA; and (c) whether the SES/HCA relationship was the
      same for Black and White women. A total of 383 women (57.4% Whites and 42.6%
      Blacks) participated in the study. Independent variables included family income,
      education levels, occupation, median income within zip code of participants'
      residence, and ethnicity. Dependent variables were the total and subscale scores
      (accessibility, accommodation, and affordability) on a measure of health care
      access. Family income was the SES variable that showed the strongest positive
      association with total health care access, and there was a significant
      interaction between occupation and ethnicity for total health care access. Unique
      relationships were observed between each SES variable and each subscale on the
      health care access measure. The overall patterns between SES and health care
      access were similar for Blacks and Whites. Results suggest that the relationship
      between health care access and SES should be investigated through a multi
      dimensional approach, and that an array of SES variables must be considered when
      designing interventions to improve health care access among healthy women.

PMID- 11289254
TI  - Upper gastrointestinal hemorrhage in African-American and Hispanic elderly
      patients.
AB  - OBJECTIVES: To investigate the frequency and etiology of upper gastrointestinal
      hemorrhage (UGIH) in African-American and Hispanic elderly patients, and to
      determine the risks and benefits of endoscopic intervention. SETTING: An inner
      city county hospital serving predominantly African-American and Hispanic
      populations. METHODS: Records of 290 patients, 65 to 95 years of age, with
      diagnosis of UGIH, were reviewed retrospectively, 12 White and 8 Asian patients
      were excluded. RESULTS: Source of bleeding remained unidentified in 25 of 270
      patients and they were also excluded. Endoscopic findings in 245 patients were:
      59 gastric ulcers, 52 duodenal ulcers, 49 gastric erosions, 37 gastroesophageal
      varices, 25 Mallory Weiss tears, 15 angiodysplasias, 13 Dieulafoy's lesions, 12
      portal hypertensive gastropathies, 8 esophageal cancers with bleeding, and 7
      gastric cancers with bleeding; 32 patients had more than one lesion. Endoscopic
      therapy was administered to 159 patients, and was helpful in stopping bleeding
      and/or delaying surgery in 102 patients. Overall, there were 59 deaths, mostly
      due to underlying multiple system disease. There was no death directly due to
      endoscopy. CONCLUSIONS: Acute UGIH in African-American and Hispanic elderly
      patients is a serious condition, associated with significant morbidity and
      mortality. Benefits of endoscopy should be offered to all such patients, and
      endoscopy should not be withheld because of age alone.

PMID- 11289255
TI  - Acculturation and breast-feeding intention and practice in Hispanic women on the
      US-Mexico border.
AB  - OBJECTIVES: To explore the extent to which acculturation indicators predict both
      breast-feeding history and intentions among Mexican-American mothers having their
      first births, and among those having subsequent births. DESIGN: Cross-sectional
      survey in a hospital post-partum unit. METHODS: 3,036 Hispanic women were
      interviewed post-partum in their hospital room. A survey was administered in
      English or Spanish, and included questions about prenatal care, diet, work
      exposures, contraceptive use, and breast-feeding history and intentions. For the
      purposes of this study, acculturation was measured using a series of indicators
      including language spoken at home, language ability, country of birth, and
      country in which last schooling was received. RESULTS: Previous breast-feeding
      was significantly associated with educational attainment, speaking both English
      and Spanish at home, having had prenatal care during the previous pregnancy, and
      with both country variables (country of birth and country where finished school).
      Women with less education, women who were single, and women who did not receive
      any prenatal care were less likely to intend to breast-feed than were women with
      a college education, women with a partner, and women who received any prenatal
      care. Women born in Mexico (for multiparous women), or having finished school in
      Mexico (for primiparous women), were more likely to intend to breast-feed.
      CONCLUSIONS: Acculturation is associated with breast-feeding history and
      intention to breast-feed. Acculturation is a complex construct and traditional
      measures of acculturation based on language preference may not be as useful on
      the US-Mexico border. It is recommended that further study be conducted to
      determine what factors prevent women from breast-feeding, even though they intend
      to do so, especially in multi-cultural communities like those around the US
      Mexico border.

PMID- 11289256
TI  - Anger expression and hypertension in transit workers.
AB  - One hypothesis in the literature on anger and hypertension is that a chronic
      tendency to suppress anger is an etiological factor in the development of
      hypertension. The present study assessed the relationship between anger
      expression and hypertension in a multicultural sample of 1,407 San Francisco bus
      drivers. Simple and multiple regression analyses revealed no significant
      differences between suppressed or expressed anger and hypertension. Thus, the
      results of this study do not support the hypothesis that suppressed anger is an
      etiological factor in hypertension.

PMID- 11289257
TI  - High blood pressure knowledge in an urban African-American community.
AB  - OBJECTIVE: To determine the level and determinants of knowledge of the risks for
      hypertension and the potential for its prevention in an urban African-American
      community. METHODS: In a survey of 397 African-American adults (18-73 years of
      age) at an urban community fair, we measured high blood pressure knowledge using
      a 12-item questionnaire designed at NIH for the assessment of high blood pressure
      knowledge among non-medical persons. RESULTS: The mean high blood pressure
      knowledge score for the overall sample was 83.1%. There were subgroup differences
      in the scores with significant associations between high blood pressure knowledge
      score and level of education (P = .002) and a personal history of hypertension (P
      = .009). CONCLUSION: We concluded that the participants exhibited a high, but
      variable, level of high blood pressure knowledge with a higher level of education
      and/or a personal history of hypertension having a significant association with
      greater blood pressure knowledge. The effects of the magnitude and mode of
      acquisition of high blood pressure knowledge on the control of high blood
      pressure and its related outcomes need to be examined in further studies.

PMID- 11289258
TI  - Ethnicity and end-of-life care: the use of feeding tubes.
AB  - BACKGROUND: Blacks utilize many health care services at lower rates than do
      Whites. However, in end-of-life care, the situation is frequently reversed, with
      Blacks using life-sustaining interventions at higher rates than do Whites. We
      investigated the use of feeding tubes in very severely cognitively impaired
      nursing-home residents, and examined the findings in light of previous studies on
      the role of ethnicity in end-of-life decision making. DESIGN AND METHODS: We
      performed a descriptive, cross-sectional population-based study of residents in
      Kansas nursing homes from January 1994 through June 1998, using Minimum Data Set
      reports. A total of 4,920 nursing home residents (4,691 White and 229 Black) with
      very severe and irreversible cognitive impairment comprised the study population.
      Factors associated with tube use were examined using bivariate and logistic
      regression tests. RESULTS: Feeding tube use was strongly associated with
      swallowing difficulties, Black race, urban location of nursing home, stroke, and
      absence of dementia in multivariate analysis. Feeding tubes were used in 10.1% of
      White subjects and in 38.9% of Black subjects for an overall rate of 11.5%.
      Feeding tube use was greater (P<.001) among Black subjects in all demographic and
      clinical sub-populations examined. CONCLUSIONS: Feeding tube use is significantly
      more common in Blacks than in Whites. These findings are consistent with
      published studies of Black-White differences in preferences for medical treatment
      at the end of life. Future research efforts should examine end-of-life decision
      making processes directly. Qualitative methods may be useful in generating new
      hypotheses regarding the role of ethnicity in these decisions.

PMID- 11289259
TI  - Studies on the supply of immunoglobulin G to newborn camel calves (Camelus
      dromedarius).
AB  - A major problem in camel productivity is the high mortality rate of camel calves
      in the first 3 months. The causes for mortality are mainly poor management
      practice and infectious diseases. The purpose of this research, carried out on a
      ranch in Kenya, was to determine the immunoglobulin G (IgG) concentration in
      camel colostrum as well as the extent of the calves' passive immunization by
      maternal antibodies. IgG concentration in colostrum and in the serum of the calf
      were measured during the first 3 d of life. Evaluation was carried out by
      comparing the respective values with those for horses and cattle. The average IgG
      concentration in the camel colostrum was higher than that found in literature for
      horses and cattle. IgG concentration in the serum of the camel calves reached its
      maximum 24 h after birth. In 39% of the examined calves, this maximum
      concentration was below 4 g/l, which is considered to be the critical value in
      horses and cattle. 61% of the calves achieved an IgG concentration of over 4 g/l.
      Since there is no correlation between IgG level in colostrum and early mortality,
      the results indicate that low colostrum intake during the first 24 h of life and
      not low IgG concentration in colostrum is presumably one of the main causes of
      early calf mortality. Therefore, it was recommended that the care of the newborn
      calves by herdsmen should be improved.

PMID- 11289260
TI  - Influence of growth conditions on heat-stable phospholipase activity in
      Pseudomonas.
AB  - Many psychrotrophic bacteria contaminating raw milk produce phospholipase that
      withstands pasteurization and UHT treatments. This enzyme acts on the milk fat
      globule membrane and exposes triacylglycerides to the action of lipase.
      Phospholipase production by various isolates of Pseudomonas was investigated. The
      isolates were cultured aerobically at 8 degrees C in nutrient broth, McKellar's
      minimal salts medium, Chrisope's medium, and skim milk. Each strain produced
      phospholipase during the 50 h incubation. Enzyme production varied significantly
      (P < 0.001) with strain and growth medium. Strains varied significantly (P <
      0.001) in their enzyme production in each medium and during the incubation time
      as well. Strain, incubation time, and the growth medium significantly influenced
      (P < 0.001) heat stability of the enzyme activity. Pasteurization reduced the
      activity, but did not eliminate it in skim milk.

PMID- 11289262
TI  - Control of Listeria monocytogenes by bacteriocins and monitoring of bacteriocin
      producing lactic acid bacteria by colony hybridization in semi-hard raw milk
      cheese.

PMID- 11289261
TI  - Proteolysis and formation of volatile compounds in cheese manufactured with a
      bacteriocin-producing adjunct culture.
AB  - Hispanico cheese, a semi-hard Spanish variety, was manufactured from a mixture of
      pasteurized cows' and ewes' milks (4:1) using a commercial mesophilic LD-type
      starter comprising Lactococcus lactis subsp. cremoris, Lc. lactis subsp. lactis,
      Lc. lactis subsp. lactis var diacetylactis and Leuconostoc mesenteroides subsp.
      cremoris. Varying amounts (0-1.0 g/kg) of an Enterococcus faecalis INIA 4 culture
      in milk were added as a bacteriocin-producing adjunct. Differences in pH between
      cheeses manufactured with and without the bacteriocin producer did not exceed
      0.11 pH units. Starter lactococci lost viability more rapidly in cheeses made
      with the bacteriocin producer, which reached counts of up to 6 x 10(7) cfu/g
      during ripening. Aminopeptidase activity in 1-d-old cheese made from milk
      inoculated with 1.0 g bacteriocin-producing culture/kg was twice that in control
      cheese. Degrees of overall proteolysis and levels of total free amino acids in 45
      d-old cheese made with 1.0 g bacteriocin-producing culture/kg were 1.80-fold and
      2.17-fold those in control cheese of the same age. Inoculating milk with 1.0 g/kg
      bacteriocin-producing culture reduced the level of hydrophobic peptides in the
      resultant cheese, increased the concentrations of 3-methyl-1-butanal, diacetyl
      and acetoin, and resulted in the highest scores for flavour quality and flavour
      intensity throughout ripening.

PMID- 11289263
TI  - Monitoring lactic acid bacteria strains during 'Cacioricotta' cheese production
      by restriction endonuclease analysis and pulsed-field gel electrophoresis.

PMID- 11289264
TI  - Effect of a differential allelic expression of kappa-casein gene on ethanol
      stability of bovine milk.

PMID- 11289265
TI  - Thrice-daily milking throughout lactation maintains epithelial integrity and
      thereby improves milk protein quality.
AB  - Cows managed for extended lactations of 16 months duration were milked on a half
      udder basis twice or thrice daily, commencing in lactation week 9. Mammary
      epithelial integrity (assessed by milk sodium : potassium ratio) was greater in
      the half-udder which was milked thrice daily. This difference was evident
      throughout the lactation but became greater after week 41. Milk protein
      composition was assessed during late lactation (52+/-3 weeks). Casein number
      (casein as a proportion of total protein) was significantly higher in half-udders
      milked thrice daily, as were the relative amounts of alpha- and beta-caseins,
      whilst those of kappa- and- caseins were reduced. Two days of inverted milking
      frequency (i.e. thrice-milked udder halves now milked twice, and vice versa) only
      partly reversed these differences. We concluded that thrice-daily milking will
      help to prevent or ameliorate the usual decline in milk processing quality
      associated with late lactation. Part of this effect is due simply to reduced
      exposure to proteolytic enzymes as a result of decreased storage time in the
      udder, but part is due to a better maintenance of epithelial tight junction
      integrity as lactation advances, which restricts leakage of proteolytic enzymes
      from serum into milk.

PMID- 11289266
TI  - Non-covalent binding of benzaldehyde to beta-lactoglobulin: characterisation by
      spectrofluorimetry and electrospray ionisation mass-spectrometry.

PMID- 11289267
TI  - Effects of intravenous infusion of amino acids and glucose on the yield and
      concentration of milk protein in dairy cows.
AB  - To test the hypothesis that the availability of glucose or its precursors can
      influence the response of milk protein concentration to the intravenous infusion
      of amino acids, five cows were used in a 5 x 5 Latin square design with period
      lengths of 7 d. The five treatments were the basal diet of grass silage ad lib.
      plus 5 kg/d of a cereal-based supplement containing feather meal (Basal); Basal
      plus 4 g/d histidine, 8 g/d methionine and 26 g/d lysine (4H); Basal plus 8 g/d
      histidine, 8 g/d methionine and 26 g/d lysine (SH); and these two amino acid
      mixtures together with 600 g/d of gluctose (4HG and 8HG respectively). Earlier
      experiments with this basal diet had shown that histidine was first-limiting for
      secretion of milk protein, followed by methionine and lysine. The yield of milk
      protein was increased progressively with the amount of histidine infused. The
      efficiency of transfer of histidine into milk protein was 0.42 for the 4H and 4HG
      and 0.35 for the 8H and 8HG treatments, and the concentration of milk protein was
      increased over Basal by all infusion treatments. However, milk protein
      concentrations were higher, and lactose concentrations in the milk were lower, in
      the absence of added glucose. Concentrations of insulin in blood plasma were not
      affected by treatment. It is concluded that, with the treatments without added
      glucose, a shortage of glucose prevented an increase in lactose secretion, and
      hence limited the increase in milk yield, leading to an increased concentration
      of protein in the milk.

PMID- 11289268
TI  - Mass spectrometry-based procedure for the identification of ovine casein
      heterogeneity.
AB  - The efficiency of reversed-phase HPLC, capillary electrophoresis (CE), PAGE and
      isoelectric focusing with immunoblotting in separating ovine caseins has been
      evaluated. The assessment was carried out by employing electrospray ionization
      mass spectrometry (ESI-MS) and matrix-assisted laser desorption ionization-time
      of flight as reference tools for identifying protein components. Ovine casein was
      fractionated by HTPC into four major peaks. With ESI-MS, each peak contained
      components belonging to only one of the four casein families. On-line liquid
      chromatography-ESI-MS allowed us to determine each fraction's composition by
      detecting thirteen alphas1-, eleven alphas2-, seven beta-, and three kappa-casein
      (CN) components. The alphas1-CN and alphas2-CN consisted of eight and two protein
      chains respectively of lengths differing through the deletion of one or more
      peptide sequences; they were also discretely phosphorylated as kappa-CN and beta
      CN. By CE at pH 2.5, each casein fraction was as heterogeneous as that resulting
      from ESI-MS for the single HPLC-derived fractions. The separation of alphas1-CN
      and alphas2-CN proved to be excellent, with the exception of a co-migration of
      kappa0-CN with a minor alphas1-CN component and of a glycosylated kappa-CN for
      with low-phosphorylated = alphas1-CN and beta-CN components. Dephosphorylation of
      whole casein was used to reduce the heterogeneity of the native fractions and by
      applying currently used analytical techniques it was possible to visualize the
      protein moiety difference along the CE profile. CE, HPLC, and immunoblotting were
      all equally capable of effecting an accurate separation of the four
      dephosphorylated casein families. The spectra obtained by ESI-MS directly on
      dephosphorylated whole ovine casein samples contained the signals of the four
      casein families and the relative alphas1-CN variants, the non-allelic alphas1-CN
      and alphas2-CN forms, dimeric kappa-CN and other newly formed peptides. We
      suggest using this procedure for rapid characterization of whole casein.

PMID- 11289269
TI  - Primary structure of kappa-casein isolated from mares' milk.
AB  - In this work the purification and the complete primary structure of kappa-casein
      from equine milk are reported for the first time. Mares' milk casein was
      separated by RP-HPLC into four fractions. Complete primary sequence was obtained
      by sequence analysis of the protein in the fastest eluting peak isolated by
      chromatography. This sequence was 95% identical to that reported for the C
      terminal portion of the zebras' kappa-casein and showed high similarity with
      kappa-caseins from sources other than Equidae, confirming that this protein was
      indeed kappa-casein in equine milk. The presence of post-translational
      modifications in equine kappa-casein was investigated by mass spectroscopy, after
      enzymic dephosphorylation. Two main components were found, the smaller component
      being more abundant. Equine kappa-casein was recognized by a lectin specific for
      one of the glucosidic bonds in the saccharide moiety of bovine kappa-casein.
      Sequence comparison with prevision studies showed that the distribution of
      charged and hydrophobic regions in equine kappa-casein was similar, but not
      identical, to that found in the bovine protein; these regions are associated with
      the role of kappa-casein in the formation and stabilization of the micellar
      structure of casein in milk.

PMID- 11289271
TI  - Influence of pH on the heat-induced proteolysis of casein molecules.
AB  - Proteolysis of sodium caseinate solution (24.5 g/l) induced by heat treatment at
      120 degrees C at different pH values was studied by measuring nitrogen content
      and relative fluorescence intensity in the 4% trichloroacetic acid filtrates. The
      low molar mass pepticles corresponding to the soluble nitrogen were identified
      using liquid chromatography/tandem mass spectrometry. Increase in proteolysis,
      deduced from the increase in soluble nitrogen content, was observed with heating
      time (10, 20 and 30 min) and pH (6.0, 7.0, 8.0 and 9.0). The fluorescence
      measurements showed that the release of peptides containing tryptophan was
      minimal at pH approximately 7.0. In parallel, eighteen low molar mass peptides
      were characterized, of which four came from kappa-casein, nine from beta-casein
      and five from alphas1-casein. Peptides were preferentially released under
      alkaline conditions.

PMID- 11289270
TI  - Effects of the CSN1A(G) allele on the clotting time of cow milk and on the
      rheological properties of rennet-curd.
AB  - The aim of this research was to study the effects of the CSN1A(G) allele on the
      main rennet coagulation properties of milk. The study was carried out on
      individual milk samples with low alphas1-casein obtained from 19 Italian Brown
      cows heterozygous for the CSN1A(G) allele (seventeen CSN1A BG and two CSN1A CG)
      from four herds in the province of Parma (Italy). Control cows (sixteen CSN1A BB
      and three CSN1A BC) giving milk with normal alphas1-casein levels were chosen
      from within the same herds in order to establish pairs of cows with identical
      environment and management conditions, and comparable lactation stages and
      numbers. Individual milk samples from single pairs of cows with somatic cell
      counts and lactose and chloride levels within the normal ranges were collected
      and analysed in parallel. Rennet coagulation properties of milk were analysed
      using Formagraph and Gel Tester. Milk from low alphas1-casein cows was
      characterized by lower casein content, lower titratable acidity and a higher
      proportion of kappa-casein in total casein. The clotting time of this milk was
      approximately 23% lower than that obtained with milk from normal alphas1-casein
      cows. Rennet curd from low alphas1-casein milk was obtained more rapidly and had
      a higher final firmness: curd-firming time was approximately 35% lower and curd
      firmness measured 30 min after rennet addition was approximately 27% higher
      compared with that for normal alphas1-casein milk. In addition, curd from low
      alphas1-casein milk had a higher resistance to compression. These results suggest
      that, although a role for the CSN2 locus cannot be definitely excluded, the
      CSN1A(G) allele can considerably affect the main rennet coagulation properties of
      milk.

PMID- 11289272
TI  - Effect of beta-lactoglobulin and precipitation of calcium phosphate on the
      thermal coagulation of milk.
AB  - The effect of beta-lactoglobulin and heat-induced precipitation of calcium
      phosphate on the pH dependence and mechanism of thermal coagulation of milk
      throughout the pH range 6.3-7.3 was studied using serum protein-free milk and
      sodium caseinate as models for micellar and non-micellar milk protein systems
      respectively. It appears that the specific effect of beta-lactoglobulin at the pH
      of maximum stability may be related to its ability to chelate calcium. The effect
      of beta-lactoglobulin at the pH of minimum stability does not appear to be
      directly related to heat-induced dissociation of K-casein or micellar integrity
      but may be due to its ability to sensitize casein micelles to heat-induced
      precipitation of calcium phosphate, by increasing micellar hydrophobicity. The
      extent of heat-induced precipitation of calcium phosphate, as a function of pH,
      is an inverse reflection of the pH dependence of heat stability. Micellar
      integrity appears to play a critical role in the heat stability of milk but for
      reasons not previously appreciated.

PMID- 11289273
TI  - Determination of somatic cells in milk by solid phase cytometry.
AB  - The somatic cell count of milk is routinely determined by the fluoro-opto
      electron method and sometimes by the direct epifluorescent filter technique
      (DEFT). This paper investigates the potential of solid phase cytometry (SPC), a
      novel technique combining aspects of both the fluoro-opto-electronic method and
      epifluorescence microscopy for somatic cell counting. In SPC, cells are retained
      on a membrane filter, fluorescently labelled and automatically detected on the
      entire membrane filter by means of a laser scanning instrument ChemScan).
      Fluorescent spots can be visually inspected by an epifluorescence microscope with
      a computer-driven moving stage. The performance of SPC was compared with that of
      the fluoro-opto-electronic method using a Fossomatic 360 instrument for 68 milk
      samples with varying somatic cell counts (10(3)-10(6)/ml). The sample throughput
      and repeatability of SPC were inferior to those of' the Fossomatic method and
      statistical analysis of the method comparison data using the approach of J. M.
      Bland & D. G. Altman (The Lancet 1986 February 8 pp 307-310) revealed a poor
      comparability between the two methods. Moreover, problems of milk filterability
      and the interference of fluorescent particles presently hamper the routine
      application of SPC. Nevertheless, this method represents the first example of the
      application of SPC to milk.

PMID- 11289274
TI  - Inactivation kinetics of alkaline phosphatase and lactoperoxidase, and
      denaturation kinetics of beta-lactoglobulin in raw milk under isothermal and
      dynamic temperature conditions.
AB  - A detailed kinetic study of alkaline phosphatase, lactoperoxidase and beta
      lactoglobulin was carried out in the context of identifying intrinsic time
      temperature indicators for controlling the heat processing of milk. The heat
      inactivation or denaturation of alkaline phosphatase, lactoperoxidase and beta
      lactoglobulin under isothermal conditions was found to follow first order
      kinetics. Experimental results were analysed using both a two step linear
      regression and a one step non-linear regression method. Results obtained using
      the two statistical techniques were comparable, but the 95% confidence interval
      for the predicted values was smaller when the one step non-linear regression
      method was used, indicating its superiority for estimating kinetic parameters.
      Thermal inactivation of alkaline phosphatase and lactoperoxidase was
      characterized by z values of 5.3 deg C (D60 degrees C = 24.6 min) and 4.3 deg C
      (D71 degrees C = 38.6 min) respectively. For the denaturation of beta
      lactoglobulin we found z values of 7.9 deg C (D7.5 degrees C = 49.9 min) in the
      temperature range 70-80 degrees C and 24.2 deg C (D85 degrees C = 3.53 min) in
      the range 83-95 degrees C. Dref and z were evaluated under dynamic temperature
      conditions. To estimate the statistical accuracy of the parameters, 90% joint
      confidence regions were constructed.

PMID- 11289275
TI  - Total mesorectal excision: assessment of the laparoscopic approach.
AB  - PURPOSE: Total mesorectal excision offers the lowest reported rates of local
      recurrence for rectal cancer; however, the ability to perform total mesorectal
      excision laparoscopically remains unproven. The aim of this study was to assess
      the feasibility and adequacy of a totally laparoscopic total mesorectal excision
      for rectal cancer. METHODS: A prospective review of all patients undergoing
      laparoscopic-assisted surgery for rectal cancer by a single surgeon was
      undertaken. These were compared with a control group undergoing open rectal
      resections by another colorectal consultant in the unit (n = 22). Comparison of
      total specimen length, longitudinal and radial excision margins, and lymph node
      yield was made between groups. RESULTS: Of 42 laparoscopic-assisted rectal
      resections attempted, 14 (33 percent) were converted to open procedures and six
      had their dissection completed open. One resection was considered noncurative.
      Twenty-one total mesorectal excisions (50 percent) were completed totally
      laparoscopically. No significant difference was detected between groups for
      specimen length, radial margin, or lymph node yield. Longitudinal margin of
      excision was longer in the laparoscopic group (4 (3.5-5) vs. 2.5 (1.05-3.5) cm; P
      = 0.02, Mann-Whitney). Operating time was significantly longer in the
      laparoscopic group (180 (168-218) vs. 125 (104-144) minutes; P = 0.003, Mann
      Whitney). Data are medians (interquartile ranges). Four patients in the
      laparoscopic-assisted group had clinical anastomotic leakage vs. one in the open
      group (P = 0.329, Fisher's exact test). At median follow-up of 38 (range, 6-53)
      months, one local recurrence had occurred in each group and crude mortality rates
      were 29 and 23 percent in the laparoscopic-assisted and open groups, respectively
      (P = 0.736, Fisher's exact test). CONCLUSION: Totally laparoscopic excision of
      the mesorectum is feasible in 50 percent of patients and where possible yields
      histologic parameters comparable to open surgery. Early survival and recurrence
      figures also appear to be comparable.

PMID- 11289276
TI  - The results of colorectal cancer treatment by p53 status: treatment-specific
      overview.
AB  - PURPOSE: Both negative and positive influences of mutant p53 on treatment outcome
      have been reported, and we present here a meta-analysis of published studies
      where outcome was reported for defined treatment groups. METHODS: We identified
      articles on the effect of p53 status by treatment modality, excluding those not
      stratified by method of treatment. A common hazard ratio was estimated from
      studies that reported a multivariate analysis. We also estimated the numbers of
      patients expressing the endpoint at the mean or median follow-up time and
      calculated a pooled odds ratio. RESULTS: Twenty-eight articles were evaluable (23
      using immunohistochemistry to detect overexpression of p53 and 8 using DNA
      sequencing), for a total of 4,416 patients. For patients treated with surgery
      only, the immunohistochemistry studies showed a significant influence of p53
      status on disease-free survival and a marginally significant influence on overall
      survival. In the studies using DNA sequencing, by contrast, there was a
      significant influence of p53 mutations on overall survival, but not disease-free
      survival. For patients treated with surgery and radiotherapy, the influence of
      p53 status on disease-free survival was either insignificant or marginally
      significant, depending on test used; there was no influence on overall survival.
      CONCLUSIONS: Although this pooled analysis of published studies where treatment
      was accounted for shows that there is a borderline significant hazard associated
      with p53 overexpression or mutation vs. p53 wild-type, it is unlikely that p53
      can be applied in a routine clinical setting alongside factors such as T stage,
      nodal status, and residual tumor, whose prognostic value is much stronger.

PMID- 11289277
TI  - Joseph M. Mathews oration: giants, heroes, comrades, and friends.

PMID- 11289278
TI  - Adenosquamous and squamous carcinoma of the colon and upper rectum: a clinical
      and histopathologic study.
AB  - PURPOSE: Squamous and adenosquamous carcinoma of the colon and proximal rectum
      are rare neoplasms in which the clinicopathologic behavior and the most
      appropriate management are unknown. The purpose of this study was to review the
      histology and clinical course of the largest series of cases ever reported from a
      single center on this rare condition. METHOD: The Mayo Clinic tissue registry was
      searched for all primary cases of squamous and adenosquamous carcinoma of the
      colon or rectum proximal to 8 cm from the dentate and presenting before December
      31, 1992. Of the 52 identified cases there was adequate histologic material for
      review in 44 cases. These cases were divided into pure squamous-cell carcinoma (n
      = 11), mixed adenosquamous carcinoma (n = 31), and adenocarcinoma with benign
      appearing squamous metaplasia (adenoacanthoma; n = 2). Squamous-cell carcinomas
      were examined for evidence of human papilloma virus by in situ hybridization. A
      retrospective review of medical records was undertaken in all 52 cases with
      respect to predisposing factors, clinicopathologic behavior, prognostic features,
      and treatment with adjuvant therapy. RESULTS: The charts of 52 patients (20
      females), with a mean age of 58.6 (range, 19-90) years, were reviewed. Right
      sided lesions were the most common (43 percent). Metastatic disease was evident
      at presentation in 49 percent of patients, the most common sites in order being
      liver, peritoneal, and lung. The five-year overall survival rate was 34 percent,
      Stage I to III disease had a 65 percent five-year survival rate, and Stage IV
      mean survival time was 8.5 months. For node-positive and node-negative disease,
      23 and 85 percent, respectively, survived five years. There was no evidence of
      human papilloma virus in the six squamous-cell carcinomas examined. CONCLUSION:
      Squamous and adenosquamous carcinomas of the colon and rectum are rare neoplasms.
      Although a poor prognosis can be expected for node-positive disease, patients
      with negative nodes do generally the same as patients with adenocarcinoma
      histology. Based on advances made with multimodality therapy of squamous-cell
      cancer of the anus and adenocarcinoma of the rectum, further studies should
      define the role of postoperative therapies for these lesions.

PMID- 11289279
TI  - Adenomatous polyps develop commonly in the ileal pouch of patients with familial
      adenomatous polyposis.
AB  - PURPOSE: The aim of this study was to establish the prevalence of adenomatous
      polyps in the ileal pouch of patients with familial adenomatous polyposis.
      METHOD: Forty-three patients who had an ileal pouch for familial adenomatous
      polyposis were invited to have a careful endoscopic examination of their pouch,
      including dye spraying. The number of polyps was recorded, and up to ten were
      biopsied. In addition, four random biopsy specimens were taken from the proximal
      and four from the distal pouch. RESULTS: Thirty-three patients with a median age
      of 36 (range, 14-63) years who had a pouch (5 Kock and 28 pelvic) for a median of
      7 (range, 1-19) years accepted the invitation. Twenty-one patients (64 percent)
      had endoscopically identified polyps, the number of polyps ranging from 1 to 100
      (median, 10) and varying in size from 1 to 3 mm. Fourteen patients (42 percent)
      had adenomatous polyps and 4 of these also had microadenomas on random biopsies.
      Nine of the 14 patients with adenomas also had lymphoid polyps. Seven patients
      had lymphoid polyps only and two of these patients had a microadenoma on random
      biopsy. Four of 12 patients with no visible polyps had microadenomas in their
      random biopsies. The presence of adenomatous polyps (Pearson's correlation; P <
      0.01) increased with the age of the pouch. In total, 20 of 33 (60 percent)
      patients had adenomas and or microadenomas. CONCLUSION: Adenomatous polyps occur
      frequently in ileal pouches. These findings are of concern, and therefore,
      regular surveillance seems warranted until the natural history of these
      adenomatous polyps is determined.

PMID- 11289280
TI  - Correlating computed tomography and positron emission tomography scan with
      operative findings in metastatic colorectal cancer.
AB  - INTRODUCTION: Several studies have been performed comparing computed tomography
      scan with positron emission tomography scan in clinical decision making.
      Unfortunately, therapeutic decisions are being made based on positron emission
      tomography scan data without a clear understanding of how well the diagnostic
      findings correlate with the clinical findings. METHODS: A retrospective review of
      41 patients with metastatic colorectal cancer was performed. All patients had
      both a computed tomography scan and a positron emission tomography scan before
      surgical exploration. All underwent surgical re-exploration. Findings were
      divided into hepatic, extrahepatic, and pelvic regions of the abdomen. Computed
      tomography scan and positron emission tomography scan findings were either
      confirmed or refuted by the operative findings. RESULTS: Positron emission
      tomography scan was found to be more sensitive than computed tomography scan when
      compared with actual operative findings in the liver (100 vs. 69 percent, P =
      0.004), extrahepatic region (90 vs. 52 percent, P = 0.015), and abdomen as a
      whole (87 vs. 61 percent, P < 0.001). Sensitivities of positron emission
      tomography scan and computed tomography scan were not significantly different in
      the pelvic region (87 vs. 61 percent, P = 0.091). In each case, specificity was
      not significantly different between the two examinations. CONCLUSION: Computed
      tomography scan and positron emission tomography scan are both diagnostic tests
      useful in the evaluation of metastatic colorectal cancer. However, positron
      emission tomography scanning is more sensitive than computed tomography scanning
      and more likely to give the correct result when actual metastatic disease is
      present.

PMID- 11289281
TI  - Prognostic significance of K-ras and TP53 mutations in the role of adjuvant
      chemotherapy on survival in patients with Dukes C colon cancer.
AB  - PURPOSE: Mutations in K-ras and TP53 genes are common in colorectal cancer. They
      affect biologic behavior and might influence chemotherapy susceptibility in these
      tumors. We investigated whether the survival of patients with Dukes C colon
      cancer treated with adjuvant chemotherapy is influenced by K-ras and TP53
      mutations. METHODS: Mutation screening of the hot spots of the K-ras gene and of
      the evolutionarily conserved regions of the TP53 gene was performed by denaturing
      gradient gel electrophoresis technique in formalin-fixed paraffin-embedded
      specimens of 55 consecutive patients with Dukes C colon cancer treated with
      adjuvant 5-fluorouracil-based chemotherapy. The median follow-up was 47 (range,
      32-66) months. RESULTS: Alterations in the mutation hot spots of K-ras were found
      at codon 12 (n = 11) and 13 (n = 4) in 15 of the 55 carcinomas (27 percent). No
      mutation was found at codon 61. Mutations of a probably causative nature in the
      evolutionarily conserved regions (exons 5-8) of the TP53 gene were found in 24
      tumors (44 percent). K-ras and TP53 mutations were found equally in the group
      with recurrent disease (7/26 (26 percent) and 12/27 (44 percent), respectively)
      and in the group without recurrences (8/28 (24 percent) and 12/28 (43 percent),
      respectively). Cancer-specific survival did not differ significantly between
      patients with K-ras or TP53 or both mutated and nonmutated tumors, respectively
      (log-rank test: K-ras, P = 0.72 and TP53, P = 0.77; K-ras and TP53, P = 0.8).
      Also, potentially aggressive K-ras codon 12 and 13 mutations had the same
      survival as tumors without these mutations (log-rank test; P = 0.73).
      CONCLUSIONS: Patients with K-ras or TP53 or both mutated Dukes C colon tumors
      have the same survival as nonmutated tumors when treated with adjuvant
      chemotherapy. These data suggest that mutations in K-ras or TP53 alone are not
      prognostic indicators in patients with Dukes C colon cancer receiving adjuvant 5
      Fluorouracil-based therapy.

PMID- 11289282
TI  - Dukes B colorectal cancer: distinct genetic categories and clinical outcome based
      on proximal or distal tumor location.
AB  - PURPOSE: The aim of this study was to determine whether tumor location proximal
      or distal to the splenic flexure is associated with distinct molecular patterns
      and can predict clinical outcome in a homogeneous group of patients with Dukes B
      (T3-T4, N0, M0) colorectal cancer. It has been hypothesized that proximal and
      distal colorectal cancer may arise through different pathogenetic mechanisms.
      Although p53 and Ki-ras gene mutations occur frequently in distal tumors, another
      form of genomic instability associated with defective DNA mismatch repair has
      been predominantly identified in the proximal colon. To date, however, the
      clinical usefulness of these molecular characteristics remains unproven. METHODS:
      A total of 126 patients with a lymph node-negative sporadic colon or rectum
      adenocarcinoma were prospectively assessed with the endpoint of death by cancer.
      No patient received either radiotherapy or chemotherapy. p53 protein was studied
      by immunohistochemistry using DO-7 monoclonal antibody, and p53 and Ki-ras gene
      mutations were detected by single strand conformation polymorphism assay.
      RESULTS: During a mean follow-up of 67 months, the overall five-year survival was
      70 percent. Nuclear p53 staining was found in 57 tumors (47 percent), and was
      more frequent in distal than in proximal tumors (55 vs. 21 percent; chi-squared
      test, P < 0.001). For the whole group, p53 protein expression correlated with
      poor survival in univariate and multivariate analysis (log-rank test, P = 0.01;
      hazard ratio = 2.16; 95 percent confidence interval = 1.12-4.11, P = 0.02).
      Distal colon tumors and rectal tumors exhibited similar molecular patterns and
      showed no difference in clinical outcome. In comparison with distal colorectal
      cancer, proximal tumors were found to be statistically significantly different on
      the following factors: mucinous content (P = 0.008), degree of histologic
      differentiation (P = 0.012), p53 protein expression, and gene mutation (P = 0.001
      and 0.01 respectively). Finally, patients with proximal tumors had a marginally
      better survival than those with distal colon or rectal cancers (log-rank test, P
      = 0.045). CONCLUSION: In this series of Dukes B colorectal cancers, p53 protein
      expression was an independent factor for survival, which also correlated with
      tumor location. Eighty-six percent of p53-positive tumors were located in the
      distal colon and rectum. Distal colon and rectum tumors had similar molecular and
      clinical characteristics. In contrast, proximal neoplasms seem to represent a
      distinct entity, with specific histopathologic characteristics, molecular
      patterns, and clinical outcome. Location of the neoplasm in reference to the
      splenic flexure should be considered before group stratification in future trials
      of adjuvant chemotherapy in patients with Dukes B tumors.

PMID- 11289283
TI  - Rectal cancer: local recurrence after surgery without radiotherapy.
AB  - PURPOSE: This study was designed to assess the local recurrence rate and
      prognostic factors for local recurrence in patients undergoing curative anterior
      or abdominoperineal resections without radiotherapy. METHODS: From January 1980
      to December 1996, 514 consecutive patients underwent curative resections for
      rectal cancer. We excluded those with preoperative radiotherapy (n = 23),
      postoperative radiotherapy (n = 27), local resection (n = 36), and 11 (2.1
      percent) patients who died postoperatively. The remaining 417 patients (249
      males) with a median age of 64 (range, 21-90) years were analyzed. For upper
      third lesions, mesorectal tissue was excised down to at least 5 cm below the
      tumor. Total mesorectal excision was performed for lower and middle tumors.
      Postoperative chemotherapy was limited to patients with Stage III lesions. Median
      follow-up (and 95 percent confidence interval) was (5.2 4.3-5.9) years, with 87.7
      percent of patients followed up longer than 24 months. Local recurrence was
      defined as any recurrence within the field of resection, regardless of the
      presence or absence of distant metastasis. RESULTS: Five-year local recurrence
      rate(and 95 percent confidence interval) was 9.7 (6.4-13) percent, with a median
      time to diagnosis of 15 (10-23) months. Local recurrence rates in Stages I, II,
      and III were: 3.1, 4.1, and 24.1 percent, respectively (P < 0.0001). In relation
      to node status, local recurrence rates were N0, 4.1 (1.7-6.5) percent; N1, 12.6
      (4.6-20.6) percent; N2, 32.1 (12.1-52.1) percent; and N3, 59.3 (22.5-96.1)
      percent; (P < 0.00001). Lower third tumors had a higher local recurrence rate
      than middle and upper third tumors: 17.9, 7.1, and 5.1 percent, respectively (P =
      0.002). Adjusted by stage, this difference was maintained only in Stage III
      tumors. Among lower tumors, those at 6 and 7 cm from the anal verge had a lower
      local recurrence rate than those below 6 cm (6.7 vs. 26.2 percent, respectively;
      P = 0.02). Accidental rectal perforation at or near the tumor site occurred in 12
      cases (2.9 percent), showing a strong correlation with local recurrence (P <
      0.0001). Multivariate analysis showed significant higher risk for lower third
      tumors (hazard ratio, 2.98) and positive nodes (hazard ratio, 4.78). CONCLUSIONS:
      Appropriate surgery without irradiation achieves excellent local control in N0
      rectal cancers. Node metastasis, lower third localization (especially below 6
      cm), and accidental rectal perforation at or near the tumor site are
      significantly associated with a higher local recurrence rate.

PMID- 11289284
TI  - Colorectal adenocarcinoma in patients under 45 years of age: comparison with
      older patients in a well-defined French population.
AB  - PURPOSE: Little is known about colorectal cancer in young patients at a
      population level, and the behavior, characteristics, and prognosis of such tumors
      continue to be debated. METHODS: A population-based series of 4,643 new cases of
      colorectal adenocarcinomas diagnosed between 1976 and 1996 in C te d'Or, France,
      was used to describe time trends in incidence, predisposing conditions, location,
      stage, and treatment and to evaluate the prognosis of such tumors in patients
      under 45 years of age (n = 146). Prognosis was determined using relative survival
      rates and predictive factors using a multivariate relative survival model.
      RESULTS: Before the age of 45 years, age-standardized incidence rates were 1.9
      per 100,000 in males and 1.4 per 100,000 in females. Incidence rates almost
      doubled from 1976 to 1982 and from 1983 to 1989 in both genders and stabilized
      thereafter. The frequency of predisposing conditions was significantly higher
      before the age of 45 years (11.7 vs. 0.4 percent; P < 0.001). TNM Stage III
      tumors were more frequent in younger patients, and Stage II tumors were more
      frequent in older patients. The postoperative mortality rate was lower in the 0
      to-44 age group, 2.1 percent, compared with 8.4 percent for the 45-and-over age
      group (P = 0.004). Five-year relative survival rates were 51.9, 49.2, and 41.4
      percent, respectively. In both overall and stage-for-stage comparisons, patients
      before the age of 45 years had a better survival rate than older patients. Gender
      and stage at diagnosis were the only independent prognostic factors of survival
      for young patients. CONCLUSIONS: This study confirms the high frequency of
      predisposing conditions in young patients and that young age is not a poor
      prognostic factor for colorectal cancer. This underlines the importance of family
      screening, aggressive surveillance, and treatment in the young with known
      predisposing conditions.

PMID- 11289285
TI  - Connective tissue changes in ileal Crohn's disease: relationship to disease
      phenotype and ulcer-associated cell lineage.
AB  - PURPOSE: Abnormalities of enteric collagen and smooth-muscle cell content have
      been documented in Crohn's disease. We studied the relationships among connective
      tissue changes, disease "type," and other disease features using
      immunohistochemistry and image analysis. METHODS: Twenty consecutive ileal
      resections for Crohn's disease and ten normal terminal ileal specimens were
      evaluated using conventional histopathologic examination. Monoclonal antibodies
      to smooth-muscle actin and Type III collagen fibers were used to determine the
      percentage area of the submucosa occupied by these constituents using image
      analysis. RESULTS: There were no significant differences in smooth-muscle content
      among stenosed, perforated, and ulcerated specimens. There was a significantly
      increased submucosal Type III collagen content in stenosed vs. other types. The
      only factor that correlated with smooth-muscle cell content was the amount of
      ulcer-associated cell lineage present. CONCLUSIONS: Increased deposition of Type
      III collagen fibers rather than smooth-muscle proliferation is associated with a
      stenotic phenotype. Loss of Type III collagen fibers may play a role in the
      development of perforating complications. We have found no evidence that smooth
      muscle cells are the source of Type III collagen fiber production although there
      is evidence that ulcer-associated cell lineage may be related to the stimulus
      leading to submucosal neomuscularization.

PMID- 11289286
TI  - Consecutive series of laparoscopic-assisted vs. minilaparotomy restorative
      proctocolectomies.
AB  - PURPOSE: Compared with open restorative proctocolectomy, laparoscopic procedures
      may reduce postoperative recovery times and give a more cosmetically acceptable
      scar, but operative time may be prolonged. We describe a minilaparotomy technique
      for restorative proctocolectomy and compare recovery parameters with a
      laparoscopic procedure. METHODS: A consecutive series of patients undergoing
      laparoscopic-assisted restorative proctocolectomy were compared with a subsequent
      consecutive series of patients undergoing a minilaparotomy procedure. This method
      incorporates a suprapubic incision. Mobilization of the colon is performed in the
      usual manner with visualization of less accessible areas made possible by using
      an illuminated St. Mark's retractor. Operative and recovery parameters were
      analyzed for each group retrospectively. RESULTS: Twenty-five patients were
      compared (12 in the laparoscopic group). Wound length was significantly longer in
      the open group (median, 14 vs. 8.5 cm; P < 0.01), but operative times were
      shorter (median, 120 vs. 150 minutes; P < 0.01). There were no differences in any
      of the recovery parameters analyzed, including analgesic requirements, time to
      ileostomy function, first fluid intake, time to solid diet, length of hospital
      stay, and complications. CONCLUSION: The only advantage of a laparoscopic
      assisted procedure over a minilaparotomy technique was the size of the wound. The
      minilaparotomy restorative proctocolectomy achieves the same postoperative
      recovery parameters and has a shorter operative time. This technique is
      recommended for surgeons less experienced in laparoscopy.

PMID- 11289287
TI  - Injection treatment of hemorrhoids in patients with acquired immunodeficiency
      syndrome.
AB  - PURPOSE: Patients with acquired immunodeficiency syndrome are often in poor
      general physical condition. Diarrhea and bleeding hemorrhoids frequently
      contribute to the morbidity, and patients with such problems cause an increasing
      load on many outpatient clinics. METHODS: Twenty-two patients (17 males) with
      acquired immunodeficiency syndrome had injection treatment for bleeding second
      degree to fourth-degree hemorrhoids according to standard outpatient clinic
      routines. Mean follow-up was 24 months. RESULTS: No complications were recorded.
      The treatment was successful in all patients, and no hemorrhoidectomy was
      necessary. Nineteen patients improved after their first injection, whereas 3
      patients required two to six weeks repeated treatments to improve. Four subjects
      with the longer follow-up (4 years) showed an improvement lasting 12 to 18 months
      and then required one to two treatments per year to stop recurrent bleeding.
      CONCLUSIONS: Because of their poor general condition and poor wound healing, a
      conservative approach is preferable to avoid a formal hemorrhoidectomy in
      patients with acquired immunodeficiency syndrome. Sclerotherapy seems to be an
      attractive alternative.

PMID- 11289288
TI  - Conservative treatment of acute thrombosed external hemorrhoids with topical
      nifedipine.
AB  - PURPOSE: This study was performed according to a prospective, randomized, open
      design. The aim was to test the efficacy of local application of nifedipine
      ointment in healing acute thrombosed external hemorrhoids. METHODS: Ninety-eight
      patients who gave their informed consent were recruited; they received clinical
      examination and anoscopy. A questionnaire to evaluate symptoms, pain, and
      concurrent use of analgesics was administered. Patients treated with nifedipine
      (n = 50) used topical 0.3 percent nifedipine and 1.5 percent lidocaine ointment
      every 12 hours for two weeks. The control group, consisting of 48 patients,
      received topical 1.5 percent lidocaine ointment during therapy. RESULTS: Results
      obtained were as follows: complete relief of pain in 43 patients (86 percent) of
      the nifedipine-treated group as opposed to 24 patients (50 percent) of the
      control group after 7 days of therapy (P < 0.01); oral analgesics were used by 4
      patients (8 percent) in the nifedipine-treated group as opposed to 26 patients
      (54.1 percent) of the control group after 7 days of therapy (P < 0.01); and
      resolution of acute thrombosed external hemorrhoids was achieved after 14 days of
      therapy in 46 patients (92 percent) of the nifedipine-treated group, as opposed
      to 22 patients (45.8 percent) of the control group (P < 0.01). We did not observe
      any systemic side effect in patients treated with nifedipine. CONCLUSIONS: Our
      study clearly demonstrates that the use of topical nifedipine, which at present
      is for treatment of cardiovascular disorders, is a reliable new option in the
      conservative treatment of thrombosed external hemorrhoids.

PMID- 11289289
TI  - Diagnostic use of the sentinel node in colon cancer.
AB  - PURPOSE: The aim of this study was to compare the lymphatic drainage of colon
      cancer with the anatomic distribution of histologic and submicroscopic lymph node
      metastases. METHODS: Patients attending for colectomy were eligible to enter the
      study. At the commencement of surgery, 40 MBq of 99mTc colloidal antimony sulfide
      in 2 ml of Patent Blue dye was injected subserosally around the tumor. Resection
      was completed in a standard fashion. After resection, specimens were imaged with
      a gamma camera to determine the site of sentinel lymph nodes, and then dissected,
      recording the position of the lymph nodes on an anatomic diagram. Recovered lymph
      nodes were bisected, one-half for routine histology and one-half for assessment
      by keratin 20 (K20) reverse transcription polymerase chain reaction. The kappa
      measure of agreement was used to assess concordance between sentinel nodes and
      histologic and submicroscopic metastases. RESULTS: Four hundred fifty-six lymph
      nodes were dissected from 26 tumors and evaluated using lymphoscintigraphy and
      lymph node mapping. Sentinel nodes were evident in 23 tumors (88 percent). The
      sensitivity of sentinel nodes involvement as a predictor of metastatic disease
      was 55 percent (95 percent confidence interval, 23-83), with a false negative
      (nondiagnostic) rate of 45 percent. Sentinel nodes involved the apical group in
      four tumors, and represented anatomic "skip" lesions in four tumors. CONCLUSIONS:
      Direct lymphatic drainage to the apical group does occur in colon cancer;
      however, sentinel node mapping of colon cancer by this technique is of little
      clinical value because of the poor concordance between lymph node metastases and
      sentinel nodes.

PMID- 11289290
TI  - Endoscopic transanal decompression with a drainage tube for acute colonic
      obstruction: clinical aspects of preoperative treatment.
AB  - PURPOSE: The study was undertaken to evaluate the clinical usefulness of
      endoscopic transanal decompression with a newly developed drainage tube for the
      treatment of acute colonic obstruction. METHODS: Thirty-six patients ranging in
      age from 46 to 87 years (average age = 69 years) with acute colorectal
      obstruction secondary to carcinoma were treated by means of intubation with a
      flexible drainage tube using combined endoscopic and fluoroscopic guidance. After
      tube placement, the obstructed colon was aspirated, decompressed, and cleaned
      with a 50 ml syringe and saline solution. The drainage tube was kept inserted and
      the colon was irrigated two or three times per day using 500 to 1,000 ml of
      saline until there were no contents in the colon. The colon was almost empty at
      the time of operation. The success rate, benefits, and complications of this
      technique were evaluated. RESULTS: Placement of the drainage tube was successful
      in 34 (94.4 percent) of 36 patients. Immediately after aspiration and
      decompression, symptoms related to obstruction were relieved in 21 patients (61.8
      percent), within one hour in 9 patients (26.5 percent) and within four hours in 4
      patients (11.8 percent). All 34 patients had elective single-stage surgery
      without severe complications at the anastomotic site such as anastomotic leakage
      and postanastomotic stenosis that needed treatment a few days after placement of
      the drainage tube. In the two cases of unsuccessful placement of the drainage
      tube, emergent colostomy was performed. CONCLUSION: Decompression with a
      transanal drainage tube is an easy and safe technique to relieve colonic
      obstruction effectively without any excess burden to patients. Because the
      procedure permits single-stage surgery in most cases, it is also cost effective.

PMID- 11289291
TI  - Microscopic analysis of anastomotic healing in the intestine of normal and
      diabetic rats.
AB  - PURPOSE: The mechanisms that cause diabetes to impair the development of
      anastomotic strength in the intestine are poorly understood. We investigated
      whether short-term uncontrolled diabetes causes alterations in microscopic
      aspects of anastomoses from the ileum and colon. METHODS: Eighteen Wistar rats
      were rendered diabetic one week before operation by intravenous streptozotocin
      injection (50 mg/kg), resulting in nonfasting blood glucose levels of
      approximately 20 mmol/l. Another 18 age-matched rats were used as controls with a
      normal blood glucose range of 5 to 7 mmol/l. All rats underwent resection and
      anastomosis of both the ileum and colon. Animals were killed at one, three, or
      seven days after operation. Cellular and architectural parameters of anastomotic
      healing were scored in hematoxylin and eosin-stained sections. Anastomotic
      collagen content was analyzed by image analysis in picrosirius red-stained
      sections. RESULTS: Anastomotic necrosis, edema, and epithelial recovery were not
      affected by diabetes. In diabetic rats, the number of polymorphonuclear cells and
      macrophages was significantly (P = 0.025 and 0.0002, respectively) increased in
      ileal anastomoses one and three days after operation. In colonic anastomoses, the
      number of polymorphonuclear cells was increased at one (P = 0.001) and seven (P =
      0.014) days after operation. Repair of the submucosal-muscular layer in colonic
      anastomoses from diabetic rats was impaired seven days after surgery (P =
      0.0071), but in ileal anastomoses no difference was found. In the anastomotic
      area, collagen deposition at postoperative Days 1, 3, and 7 remained unaffected
      by diabetes. CONCLUSION: Experimental diabetes leads to alterations in cellular
      components involved in the early phase of repair of intestinal anastomoses but
      not to a reduced accumulation of wound collagen.

PMID- 11289292
TI  - Harmonic scalpel in laparoscopic colorectal surgery.
AB  - PURPOSE: With advances in laparoscopy, various hemostatic procedures have been
      advocated with variable results. Using currently available tools, some steps in
      laparoscopic colorectal surgery still represent technical challenges. Our aim was
      to investigate the feasibility and reliability of the Harmonic Scalpel in
      laparoscopic colorectal surgery. METHODS: In this nonrandomized prospective
      study, 34 consecutive patients (15 males; mean age, 46 (range, 24-80) years)
      underwent laparoscopic colorectal surgery for benign disease (27 patients) and
      colorectal cancer (7 patients). Dissection, hemostasis, coagulation, and division
      of several types of vascular pedicles were performed exclusively with the
      Harmonic Scalpel. The 10-mm-blade Harmonic Scalpel device was used at full power
      mode for all purposes through a 10-mm port. Coagulation of vascular pedicles was
      always achieved with the blades in the flat position. The large pedicles
      (inferior mesenteric, right and left colic, and ileocolic) were coagulated for 20
      seconds in several locations along the length (1 cm) before final division.
      Smaller vascular pedicles were coagulated for ten seconds before division. When
      the vein and the artery of major pedicles were divided at their origin, either
      for malignancy or for technical reasons, they were dissected and coagulated
      separately. For more limited resection of the mesentery, as in the case of benign
      disease, vascular pedicles were coagulated together as a single bundle. Operative
      time, minor or major intraoperative or postoperative hemorrhage, need for
      conversion to laparotomy, bowel injury, and trocar complications were recorded.
      All anastomoses were checked on Day 8 by a diatrizoate sodium enema. RESULTS:
      There was no mortality. Mean operative time was 276 (range, 200-520) minutes.
      Neither minor nor uncontrollable hemorrhage occurred; no conversion to laparotomy
      and no vascular or bowel injury were recorded. There was one port-site hematoma.
      Neither hemoperitoneum, intraperitoneal hematoma, fistula, nor intra-abdominal
      abscess was observed. CONCLUSION: Coagulation and division of minor as well as
      major vascular pedicles in laparoscopic colorectal surgery with the Harmonic
      Scalpel" are technically easy, feasible, and reliable.

PMID- 11289293
TI  - Role of molecular diagnostic testing in familial adenomatous polyposis and
      hereditary nonpolyposis colorectal cancer families.
AB  - PURPOSE: Genetic tests are available for familial adenomatous polyposis and
      hereditary nonpolyposis colorectal cancer. The goal of this review was to develop
      an algorithm for application of molecular diagnostic techniques to the management
      of hereditary colorectal carcinoma and to familiarize the clinician with the
      vocabulary of molecular genetic testing for hereditary colorectal carcinoma.
      METHODS: Studies examining the clinical use of genetic testing for hereditary
      colorectal carcinoma syndromes are evaluated. Recent advances in molecular
      genetic technology are reviewed, and clinical management as practiced here and
      elsewhere is outlined. RESULTS: This review is a guide to the most reliable
      molecular diagnostic techniques. Three key questions are answered: who, when, and
      how to test. CONCLUSIONS: When integrated with existing testing protocols for
      colorectal carcinoma and when applied with appropriate caveats, particularly
      regarding interpretation of negative results, genetic testing can result in
      improved management of patients and families.

PMID- 11289294
TI  - Tailgut cyst invaded by rectal cancer through an anal fistula: report of a case.
AB  - Rectal cancer accompanying or developing in a tailgut cyst has been reported.
      However, there have been no reports of cases such as the present one, a tailgut
      cyst invaded by a rectal cancer.

PMID- 11289295
TI  - Primary low-grade B cell non-Hodgkin's lymphoma of MALT type simultaneously
      arising in the colon and in the lung: report of a case.
AB  - zone B cell lymphoma of mucosa-associated lymphoid tissue type according to the
      Revised European American Lymphoma classification). Other mucosa-associated
      lymphoid tissue-type lymphomas arise in the salivary glands, thyroid gland, and
      in the lung (bronchus-associated lymphoid tissue). Here, we report the first case
      of a monoclonal mucosa-associated lymphoid tissue lymphoma with simultaneous
      manifestation in the colonic and bronchial mucosa in a 62-year-old patient. With
      mitoxantrone, chlorambucil, and prednisone polychemotherapy, a complete year-long
      remission was achieved.

PMID- 11289296
TI  - Rectal localization of metastatic lobular breast cancer: report of a case.
AB  - The incidence of extrahepatic gastrointestinal metastases from breast cancer is
      reported in the literature only as necroscopy studies (6-18 percent); they
      usually originate from lobular or a mixed ductal-lobular subtype. Nonspecific
      presenting symptoms, death of the patients caused by other more frequent
      metastases, and variable radiographic features mimicking primary neoplasms cause
      a clinical underestimation of this pathology. We report here a case of rectal
      metastasis from a lobular carcinoma eight years after mastectomy.

PMID- 11289297
TI  - Pouch adenomas after ileal pouch-anal anastomosis for familial adenomatous
      polyposis.

PMID- 11289298
TI  - Introduction: nitrate reduction and the nitrogen cycle.

PMID- 11289299
TI  - Functional, biochemical and genetic diversity of prokaryotic nitrate reductases.
AB  - Prokaryotic nitrate reduction can serve a number of physiological roles and can
      be catalysed by a number of biochemically distinct nitrate reductases. Three
      distinct nitrate reductase classes can be indentified in prokaryotes, NAS, NAR
      and NAP. NAS is located in the cytoplasmic compartment and participates in
      nitrogen assimilation. NAR is usually a three-subunit complex anchored to the
      cytoplasmic face of the membrane with its active site located in the cytoplasmic
      compartment and is involved in anaerobic nitrate respiration. NAP is a two
      subunit complex, located in the periplasmic compartment, that is coupled to
      quinol oxidation via a membrane anchored tetraheme cytochrome. It shows
      considerable functional flexibility by participating in anaerobic respiration or
      redox energy dissipation depending on the organism in which it is found. The
      members of all three classes of enzymes bind the bis-molybdopterin guanine
      dinucleotide cofactor at the active site, but they differ markedly in the number
      and nature of cofactors used to transfer electrons to this site. Analysis of
      prokaryotic genome sequences available at the time of writing reveals that the
      different nitrate reductases are phylogenetically widespread.

PMID- 11289300
TI  - The coordination and function of the redox centres of the membrane-bound nitrate
      reductases.
AB  - Under anaerobic conditions and in the presence of nitrate, the facultative
      anaerobe Escherichia coli synthesises an electron-transport chain comprising a
      primary dehydrogenase and the terminal membrane-bound nitrate reductase A
      (NarGHI). This review focuses on recent advances obtained on the structure and
      function of the three protein subunits of membrane-bound nitrate reductases. We
      discuss a global architecture for the Mo-bisMGD-containing subunit (NarG) and a
      coordination model for the four [Fe-S] centres of the electron-transfer subunit
      (NarH) and for the two b-type haems of the anchor subunit NarI.

PMID- 11289301
TI  - Structure and function of eukaryotic NAD(P)H:nitrate reductase.
AB  - Pyridine nucleotide-dependent nitrate reductases (NRs; EC 1.6.6.1-3) are
      molybdenum-containing enzymes found in eukaryotic organisms which assimilate
      nitrate. NR is a homodimer with an approximately 100 kDa polypeptide which folds
      into stable domains housing each of the enzyme's redox cofactors--FAD, heme-Fe
      molybdopterin (Mo-MPT) and the electron donor NAD(P)H--and there is also a domain
      for the dimer interface. NR has two active sites: the nitrate-reducing Mo
      containing active site and the pyridine nucleotide active site formed between the
      FAD and NAD(P)H domains. The major barriers to defining the mechanism of
      catalysis for NR are obtaining the detailed three-dimensional structures for
      oxidized and reduced enzyme and more in-depth analysis of electron transfer rates
      in holo-NR. Recombinant expression of holo-NR and its fragments, including site
      directed mutagenesis of key acative site and domain interface residues, are
      expected to make large contributions to this effort to understand the catalytic
      mechanism of NR.

PMID- 11289302
TI  - Regulation of plant NR activity by reversible phosphorylation, 14-3-3 proteins
      and proteolysis.
AB  - This review highlights progress in dissecting how plant nitrate reductase (NR)
      activity is regulated by Ca2+, protein kinases, protein kinase kinases, protein
      phosphatases, 14-3-3 proteins and protease(s). The signalling components that
      regulate NR have also been discovered to target other enzymes of metabolism,
      vesicle trafficking and cellular signalling. Extracellular sugars exert a major
      impact on the 14-3-3-binding status and stability of many target proteins,
      including NR in plants, whereas other stimuli affect the regulation of some
      targets and not others. We thus begin to see how selective or global switches in
      cellular behaviour are triggered by regulatory networks in response to different
      environmental stimuli. Surprisingly, the question of how changes in NR activity
      actually affect the rate of nitrate assimilation is turning out to be a tough
      problem.

PMID- 11289303
TI  - Nitrate and nitrite transport in bacteria.
AB  - The topological arrangements of nitrate and nitrite reductases in bacteria
      necessitate the synthesis of transporter proteins that carry the nitrogen
      oxyanions across the cytoplasmic membrane. For assimilation of nitrate (and
      nitrite) there are two types of uptake system known: ABC transporters that are
      driven by ATP hydrolysis, and secondary transporters reliant on a proton motive
      force. Proteins homologous to the latter type of transporter are also involved in
      nitrate and nitrite transport in dissimilatory processes such as denitrification.
      These proteins belong to the NarK family, which is a branch of the Major
      Facilitator Superfamily. The mechanism and substrate specificity of transport via
      these proteins is unknown, but is discussed in the light of sequence analysis of
      members of the NarK family. A hypothesis for nitrate and nitrite transport is
      proposed based on the finding that there are two distinct types of NarK.

PMID- 11289304
TI  - Eukaryotic nitrate and nitrite transporters.
AB  - Nitrate transport is the key step controlling the amount of nitrate incorporated
      by the cells and subsequent of storage, reduction or export. Molecular, genetic
      and biochemical approaches to the study of eukaryotic nitrate/nitrite
      transporters allow an initial understanding of this step, which is much more
      complex and structured than previously suspected. At the plasma membrane level,
      two gene families, Nrt1 and Nrt2, account for high- and low-affinity nitrate
      transporters. Functionality of NRT1 from Arabidopsis and NRT2 proteins from
      Aspergillus and Chlamydomonas has been demonstrated. However, redundancy of these
      systems makes it difficult to assign particular physiological roles to each. Data
      on genes involved in the regulation of nitrate transport and reduction are still
      scarce. Information on nitrite transporters to the chloroplast is biased by the
      belief that in vivo nitrous acid diffuses freely to this organellum. The recent
      progress on these aspects is discussed in this review.

PMID- 11289305
TI  - Crystallization of RNA.
AB  - Even as the number of RNA structures determined and under study multiplies, the
      critical step in X-ray diffraction analysis, growth of single well-ordered
      crystals, remains at the boundary between art and science. Recent advances in
      methods of RNA synthesis, purification, and characterization, as well as
      empirical and technical improvements in crystallization techniques, the
      development of cryo-crystallography, and the wider availability of bright,
      tunable, X-rays from synchrotron sources are improving the chances of obtaining
      RNA crystals suitable for X-ray structural analysis. In this review, we summarize
      the current status of the design, preparation, purification, and analysis of RNA
      for crystallization and describe the latest approaches to obtaining diffraction
      quality crystals.

PMID- 11289306
TI  - Polyamines in cell growth and cell death: molecular mechanisms and therapeutic
      applications.
AB  - Polyamines are aliphatic cations with multiple functions and are essential for
      life. Cellular polyamine levels are regulated by multiple pathways such as
      synthesis from amino acid precursors, cellular uptake mechanisms that salvage
      polyamines from diet and intestinal microorganisms, as well as stepwise
      degradation and efflux. Investigations using polyamine biosynthetic inhibitors
      indicate that alterations in cellular polyamine levels modulate normal and cancer
      cell growth. Studies using transgenic mice overexpressing polyamine biosynthetic
      enzymes support a role of polyamines in carcinogenesis. Many, if not all, signal
      transduction pathways intersect with polyamine biosynthetic pathways and the
      regulation of intracellular polyamine levels. Direct binding of polyamines to DNA
      and their ability to modulate DNA-protein interactions appear to be important in
      the molecular mechanisms of polyamine action in cell proliferation. Consistent
      with the role of polyamines as facilitators of cell growth, several studies have
      shown their ability to protect cells from apoptosis. However, polyamines also
      have a role in facilitating cell death. The basis of these diverse cellular
      responses is currently not known. Cell death response might be partly mediated by
      the production of hydrogen peroxide during polyamine catabolism. In addition, the
      ability of polyamines to alter DNA-protein and protein-protein interactions might
      be disruptive to cellular functions, when abnormally high levels are accumulated
      due to defects in polyamine catabolic or efflux pathways. A large body of data
      indicates that polyamine pathway can be a molecular target for therapeutic
      intervention in several types cancers. Inhibitors of biosynthesis, polyamine
      analogues as well as oligonucleotide/polyamine analogue combinations are
      promising drug candidates for chemoprevention and/or treatment of cancer.

PMID- 11289307
TI  - The pathogenesis of transmissible spongiform encephalopathy: routes to the brain
      and the erection of therapeutic barricades.
AB  - Classical and modern studies of the pathogenesis of transmissible spongiform
      encephalopathy are reviewed, with particular attention paid to recent
      investigations of the routes of neuroinvasion. In various experimental models, a
      heirarchy of paths to the brain includes direct neural transit from the site of
      infection, replication in the spleen and neural entry through the spinal cord,
      and hematogenous spread. Possible modes and sites of therapeutic intervention are
      suggested.

PMID- 11289308
TI  - HuR and mRNA stability.
AB  - An important mechanism of posttranscriptional gene regulation in mammalian cells
      is the rapid degradation of messenger RNAs (mRNAs) signaled by AU-rich elements
      (AREs) in their 3' untranslated regions. HuR, a ubiquitously expressed member of
      the Hu family of RNA-binding proteins related to Drosophila ELAV, selectively
      binds AREs and stabilizes ARE-containing mRNAs when overexpressed in cultured
      cells. This review discusses mRNA decay as a general form of gene regulation,
      decay signaled by AREs, and the role of HuR and its Hu-family relatives in
      antagonizing this mRNA degradation pathway. The influence of newly identified
      protein ligands to HuR on HuR function in both normal and stressed cells may
      explain how ARE-mediated mRNA decay is regulated in response to environmental
      change.

PMID- 11289309
TI  - Molecular genetic analysis of the calcineurin signaling pathways.
AB  - Calcineurin is a Ca2+- and calmodulin-regulated protein phosphatase that is
      important in Ca2+-mediated signal transduction. Recent application of the
      powerful techniques of molecular genetics has demonstrated that calcineurin is
      involved in the regulation of critical biological processes such as T cell
      activation, muscle hypertrophy, memory development, glucan synthesis, ion
      homeostasis, and cell cycle control. Notably, specific transcription factors have
      been shown to play a key role in regulating these functions, and their
      calcineurin-mediated dephosphorylation and nuclear translocation appear to be a
      central event in the signal transduction pathways. This review focuses on recent
      progress in these areas and discusses the evidence for cross-talk between
      calcineurin and other signaling pathways.

PMID- 11289310
TI  - Transcriptional coregulators of the nuclear receptor superfamily: coactivators
      and corepressors.
AB  - Nuclear receptors, many of which undergo a major conformational change upon
      binding specific ligand, belong to a superfamily of proteins that bind to
      specific DNA sequences and control gene transcription. They regulate the assembly
      of a transcriptional preinitiation complex at the promoter of target genes and
      modulate their expression in response to ligand. In particular, nuclear receptors
      repress or stimulate transcription by recruiting corepressor or coactivator
      proteins, in addition to directly contacting the basal transcription machinery.
      In this review, we discuss recent progress in studies of these transcriptional
      coregulators of nuclear receptors.

PMID- 11289311
TI  - Analysis of nuclear apoptotic process in a cell-free system.
AB  - We report an analysis of the apoptotic process of mouse liver nuclei induced in a
      cell-free carrot cytosol system by cytochrome c. Typical characteristics of
      apoptosis were observed, such as chromatin condensation, margination, apoptotic
      bodies and DNA ladders. Furthermore, transmission and scanning electron
      microscope analysis of the apoptotic nuclei detected chromatin-free nuclear
      vesicles before apoptotic bodies appeared at a comparatively late phase. When AC
      YVAD-CHO, an inhibitor of caspase 6, was introduced into the system, these
      vesicles and apoptotic bodies disappeared completely within our study sections.
      We confirmed the results using whole-mount electron microscopy, and found that
      although the nuclear lamina was destroyed early, the nuclear matrix largely
      remained intact during the course of apoptosis. The nuclear matrix played an
      important role in maintaining the integrity of apoptotic cells and connecting the
      apoptotic bodies and apoptotic nucleus.

PMID- 11289312
TI  - Identification of proteins in human prostate tumor material by two-dimensional
      gel electrophoresis and mass spectrometry.
AB  - Protein patterns in cells collected from benign prostatic tissues and prostate
      carcinomas were analyzed using two-dimensional polyacrylamide gel electrophoresis
      and mass spectrometry. Polypeptide expression was evaluated by computer-assisted
      image analysis (PDQUEST). Proteins expressed by prostate tumors were identified
      via in-gel digestion and subsequent matrix-assisted laser desorption/ionization
      mass spectrometry. In addition to cytoskeletal and mitochondrial proteins, a 40
      kDa protein was identified as prostatic acid phosphatase (PAP). PAP expression
      decreased approximately twofold between benign and malignant tissue. Increased
      expression of heat shock protein 70 and decreased expression of tropomyosin 1
      were also observed in the malignant tissue. The analysis of prostate material by
      two-dimensional gel electrophoresis and mass spectrometry shows that particular
      proteins are of interest as markers of disease.

PMID- 11289313
TI  - Native skeletal muscle dihydropyridine receptor exists as a supramolecular triad
      complex.
AB  - One of the central elements of excitation-contraction coupling, the voltage
      sensing dihydropyridine receptor, is believed to exist as a high-molecular-mass
      complex in the triad junction. Although freeze-fracture electron microscopical
      analysis suggests a tetrad complex, no direct biochemical evidence exists
      demonstrating the actual size of the native membrane complex. Using a combination
      of various two-dimensional gel electrophoresis techniques, we show here that the
      principal alpha1-subunit of the dihydropyridine receptor and its auxiliary alpha2
      subunit form a triad complex of approximately 2800 kDa under native conditions.
      Established Ca2+-ATPase tetramers and calsequestrin monomers were employed for
      the internal standardization of the gel systems used. Thus, the large voltage
      sensing complex appears to be tightly associated, since it does not disintegrate
      during subcellular fractionation and native electrophoresis procedures. Our
      findings support the cell biological hypothesis that native dihydropyridine
      receptor units form a tetrad structure within the transverse tubules.

PMID- 11289314
TI  - Assessment of natural products in the Drosophila melanogaster B(II) cell bioassay
      for ecdysteroid agonist and antagonist activities.
AB  - Ecdysteroid agonist and antagonist activities can be detected and quantified with
      the Drosophila melanogaster B(II) cell bioassay. This bioassay is convenient,
      sensitive and robust. We report the assessment with this bioassay of the
      activities of a wide range of compounds representing a number of classes of
      natural products. Many compounds were inactive over a wide concentration range
      (10(-8) to 10(-4) or 10(-3) M) or cytotoxic at high concentrations. However,
      antagonisitic activity was associated with several classes of compounds:
      cucurbitacins and withanolides (extending previous findings) and phenylalkanoids
      and certain alkaloids (described for the first time). A withanolide (withaperuvin
      D) is identified which possesses agonistic activity. Brassinosteroids, which have
      been ascribed (ant)agonistic properties in the past, were not found to be active
      in the B(II) bioassay, either as agonists or antagonists. Possible reasons for
      the prevalence of antagonists and for the low potency of the majority of them are
      discussed.

PMID- 11289315
TI  - Cryo-bioorganic chemistry: freezing effect on stereoselection of L- and DL
      leucine cooligomerization in aqueous solution.
AB  - The chirality of L-/DL-leucine (50-50%) cooligomerization was investigated in
      liquid and frozen aqueous solutions. Cooligomerization was carried out by
      carbonyldiimidazole activation without initiator at an ambient (+ 22 degrees C)
      and frozen (- 18 degrees C) temperature, respectively. The separated samples
      obtained after different time intervals of treatment were completely hydrolyzed
      (HCl) and the diastereomeric L- and D-leucine derivates of Marfey's reagent (1
      fluoro-2,4-dinitrophenyl-5-L-alanine amide) were then traced and evaluated by RP
      HPLC analysis. After 9 days of oligomerization, the L-Leu content was slightly
      enhanced in the liquid (57%) and somewhat more enhanced in the frozen (64%)
      samples. After 17 days, however, the L-Leu content had decreased in the liquid
      (53%) and frozen (56%) conditions. These L-enantiomer amplifications indicate
      that an L-antipode is preferentially incorporated into the alpha-helical turn of
      the oligomer in the earlier stage of cooligomerization, while, later, the D
      antipode is also incorporated. The role of ice in the improved stereoselection is
      discussed. This is the first recorded example of the effect of freezing on
      stereoselection.

PMID- 11289316
TI  - Lead exposure in children living in a smelter community in region Lagunera,
      Mexico.
AB  - Industrial growth has created the potential for environmental problems in Mexico,
      since attention to environmental controls and urban planning has lagged behind
      the pace of industrialization. The aim of this cross-sectional study was to
      assess lead exposure in children aged 6-9 yr attending 3 primary schools and
      living in the vicinity of the largest smelter complex in Mexico. One of the
      schools is located 650 m distant from a smelter complex that includes a lead
      smelter (close school); the second is located 1750 m away from the complex and at
      the side of a heavy traffic road (intermediate school) in Torreon, Coahuila. The
      third school is located in Comez Palacio, Durango, 8100 m away from the smelter
      complex and distant from heavy vehicular traffic or industrial areas (remote
      school). Lead was measured in air, soil, dust, and well water. Lead in blood
      (PbB) was determined in 394 children attending the above mentioned schools.
      Determinations were performed by atomic absorption spectrometry. Diet,
      socioeconomic status, hygienic habits, and other variables were assessed by
      questionnaire. Median (range) PbB values were 7.8 microg/dl (3.54-29.61) in the
      remote school, 21.8 microg/dl (8.37-52.08) in the intermediate school and 27.6
      microg/dl (7.37-58.53) in children attending the close school. The percentage of
      children with PbB > 15 microg/dl was 6.80%, 84.9%, and 92.1% respectively. In
      this order, the geometric means (range) of Pb concentrations in air were 2.5
      microg/m3 (1.1-7.5), 5.8 microg/m3 (4.3-8.5), and 6.1 microg/m3 (1.6-14.9). The
      Pb concentrations in dust from playgrounds areas in the intermediate and close
      school settings ranged from 1,457 to 4,162.5 mg/kg. Pb concentrations in drinking
      water were less than 5 microg/L. Soil and dust ingestion and inhalation appear to
      be the main routes of exposure. Our results indicate that environmental
      contamination has resulted in an increased body burden of Pb, suggesting that
      children living in the vicinity of the smelter complex are at high risk for
      adverse effects of lead.

PMID- 11289317
TI  - Effects of nickel chloride on human platelets: enhancement of lipid peroxidation,
      inhibition of aggregation and interaction with ascorbic acid.
AB  - This study was undertaken to examine the effects of nickel (Ni) on human platelet
      function. In a (concentration-dependent manner, Ni significantly inhibited the
      function of platelet aggregation induced by collagen. The phenomenon of lipid
      peroxidation was involved as Ni significantly increased malondialdehyde (MDA)
      levels with reduction in platelet reduced glutathione (GSH) and alpha-tocopherol
      content. Further, platelet thromboxane B2, formation was markedly inhibited and
      the levels of cyclic AMP were significantly elevated by Ni. Treatment with
      ascorbic acid (Vit C) significantly lowered the levels of MDA and increased the
      content of alpha-tocopherol and reduced GSH. Vit C also significantly increased
      platelet aggregation and thromboxane B2 when coincubated with Ni. Data show that
      Ni is toxic as evidenced by lipid peroxidative damage and inhibition of human
      platelet aggregation, but that ascorbic acid provides protection, at least
      partially, against this metal.

PMID- 11289318
TI  - Physiologically based pharmacokinetic modeling of benzene metabolism in mice
      through extrapolation from in vitro to in vivo.
AB  - Benzene (C6H6) is a highly flammable, colorless liquid. Ubiquitous exposures
      result from its presence in gasoline vapors, cigarette smoke, and industrial
      processes. Benzene increases the incidence of leukemia in humans when they are
      exposed to high doses for extended periods; however, leukemia risks in humans at
      low exposures are uncertain. The exposure-dose-response relationship of benzene
      in humans is expected to be nonlinear because benzene undergoes a series of
      metabolic transformations, detoxifying and activating, in the liver, resulting in
      multiple metabolites that exert toxic effects on the bone marrow. We developed a
      physiologically based pharmacokinetic model for the uptake and elimination of
      benzene in mice to relate the concentration of inhaled and orally administered
      benzene to the tissue doses of benzene and its key metabolites, benzene oxide,
      phe nol, and hydroquinone. As many parameter values as possible were taken from
      the literature; in particular, metabolic parameters obtained from in vitro
      studies with mouse liver were used since comparable parameters are also available
      for humans. Parameters estimated by fitting the model to published data were
      first-order rate constants for pathways lacking in vitro data and the
      concentrations of microsomal and cytosolic protein, which effectively alter
      overall enzyme activity. The model was constrained by using the in vitro
      metabolic parameters (maximum velocities, first-order rate constants, and
      saturation parameters), and data from multiple laboratories and experiments were
      used. Despite these constraints and sources of variability, the model simulations
      matched the data reasonably well in most cases, showing that in vitro metabolic
      constants can be successfully extrapolated to predict in vivo data for benzene
      metabolism and dosimetry. Therefore in vitro metabolic constants for humans can
      subsequently be extrapolated to predict the dosimetry of benzene and its
      metabolites in humans. This will allow us to better estimate the risks of adverse
      effects from low-level benzene exposures.

PMID- 11289319
TI  - Evaluation of the gender differences in 4,4'-methylenedianiline toxicity,
      distribution, and effects on biliary parameters.
AB  - Exposure to 4,4'-diaminodiphenylmethane (DAPM) has been linked to jaundice, toxic
      hepatitis, cholangitis, and cholestasis. In rodents, DAPM initially injures
      biliary epithelial cells, and toxicity is greater in female than male rats. Our
      goal was to determine if gender differences in DAPM toxicity were due to
      differences in biliary excretion or covalent binding of DAPM metabolites in the
      liver. Bile duct-cannulated female and male Sprague-Dawley rats were gavaged with
      vehicle or with 25 or 50 mg [14C]DAPM/kg, and bile was collected for 6 h. Serum
      and bile indicators of hepatobiliary toxicity were assessed, and radioactivity
      was measured in bile, serum, urine, and liver. At the 25 mg/kg dose, serum
      parameters were elevated only in female rats, while increases in serum parameters
      were observed in both genders at the 50 mg/kg dose. In males rats, biliary
      constituents altered by DAPM [inorganic phosphate (Pi), glucose, gamma-glutamyl
      transpeptidase (GGT)] showed time- and dose-dependent responses. In female rats,
      however, biliary constituents showed either minimal dose-response effects
      (glucose), were increased equivalently at both doses (Pi), or were not altered by
      DAPM treatment (GGT). At the 50 mg/kg dose, liver alkaline phosphatase decreased
      in female but not male rats. Gender also affected the disposition of DAPM
      metabolites. At 25 mg DAPM/ kg, male rats had greater amounts of DAPM/metabolite
      in bile and liver, while females had greater amounts in serum and urine. These
      studies thus confirm that (1) DAPM is more toxic in female than male rats, and
      (2) gender has a significant effect on the disposition and biliary excretion of
      DAPM metabolites.

PMID- 11289320
TI  - Suppression of pulmonary antibacterial defenses mechanisms and lung damage in
      mice exposed to fluoride aerosol.
AB  - In endemic fluorosis areas in China associated with coal burning, indoor airborne
      fluoride pollution is severe. To determine the effects of fluoride aerosols on
      pulmonary antibacterial defense mechanisms and lung damage, mice were exposed to
      various concentrations of fluoride aerosol (2, 5, or 10 mg/m3) or filtered air
      (control) for 14 d, 4 h/d in an inhalation chamber. Bactericidal activity against
      Staphylococcus aureus in the lung and the number and profile of free pulmonary
      cells, protein content, and lactate dehydrogenase (LDH) activity in
      bronchoalveolar lavage (BAL) fluid were assessed. Urinary fluoride concentration,
      an indicator of fluoride exposure, increased in proportion to fluoride aerosol
      concentration in the chamber. Wet lung weight was significantly higher on d 14 in
      mice exposed to 10 mg/m3 than in controls. Pulmonary bactericidal activity
      against S. aureus was concentration-dependently suppressed at 5 and 10 mg/m3
      fluoride. The number of alveolar macrophages (AMs) in the BAL fluid of the mice
      not bacterially challenged decreased significantly at 10 mg/m3 fluoride. The
      number of polymorphonuclear leukocytes and lymphocytes increased significantly at
      10 mg/m3 fluoride exposure. The concentration of total protein (TP) and albumin
      in BAL supernatant increased significantly at 5 and 10 mg/m3 fluoride exposure,
      and LDH activity rose markedly at the higher fluoride concentration. Data
      indicate that fluoride inhalation produces pulmonary cellular alterations that
      are associated with a diminished ability to cope with infectious bacteria.

PMID- 11289321
TI  - Evaluation of the wheezy infant.
AB  - BACKGROUND: The infant with persistent or recurrent wheezing during the first 2
      years of life poses a diagnostic dilemma, which can be a source of anxiety to
      both physicians and parents. A suggested diagnostic approach to the causes of
      infantile wheezing is outlined. OBJECTIVES: 1. To review the physiologic
      considerations of the infant's airways that predispose to wheezing. 2. To discuss
      the key physical findings, family history, and risk factors associated with
      wheezing in infants. 3. To develop a rational approach to the differential
      diagnosis and management of infantile wheezing. DATA SOURCES: The MEDLINE
      database as well as our clinical experience pertaining to infantile wheezing.
      CONCLUSIONS: This review discusses the diagnostic evaluation and treatment of the
      wheezing infant. We suggest that infant pulmonary function testing may be used as
      one diagnostic aid in the workup of the wheezing infant.

PMID- 11289322
TI  - Impact of the physician's participatory style in asthma outcomes and patient
      satisfaction.
AB  - OBJECTIVES: To identify factors associated with asthma patients' perceptions of
      the propensity of pulmonologists to involve them in treatment decision-making,
      and its association with asthma outcomes. DESIGN: Cross-sectional observational
      study performed from June 1995 to December 1997. SETTING: Pulmonary unit of a
      university teaching hospital. PATIENTS: Adult patients with asthma (n = 128).
      MEASUREMENTS AND RESULTS: By patient self-report, mean physician's participatory
      decision-making (PDM) style score was 72 (maximum 100, 95% CI 65, 79). PDM scores
      were significantly correlated (P < .0001) with the duration of clinic visits (r =
      .63), patient satisfaction (r = .53), duration of tenure of doctor-patient
      relationship (r = .37), and formal education (r = .22, P = .023). Significantly
      higher PDM style scores were reported when visits lasted longer than 20 minutes
      and when a patient had a >6-month relationship with a particular doctor. PDM
      scores were also significantly correlated with possession of a written asthma
      action plan (r = .54, P < .0001), days affected by asthma (r = .36, P = .0001),
      asthma symptoms (r = .23, P = .017), and preferences for autonomy in asthma
      management decisions (r = .28, P = .0035). Those with PDM scores <50 reported
      significantly lower quality of life for all domains of a disease-specific
      instrument and the Short-Form 36 health survey version 1.0. In multiple
      regression analysis, PDM style was associated with the length of the office visit
      and the duration of tenure of the physician-patient relationship (R2 = 0.47, P =
      .0009). The adjusted odds ratio, per standard deviation decrease in PDM scores,
      for an asthma hospitalization was 2.0 (95% CI 1.2, 3.2) and for rehospitalization
      was 2.5 (95% CI 1.2, 4.2). CONCLUSIONS: Patients' report of their physician's PDM
      style is significantly associated with health-related quality of life, work
      disability, and recent need for acute health services. Organizational factors,
      specifically longer visits and more time seeing a particular physician, are
      independently associated with more participatory visits. This has significant
      policy implications for asthma management.

PMID- 11289323
TI  - Evaluation of Th1/Th2 ratio and cytokine production profile during acute
      exacerbation and convalescence in asthmatic children.
AB  - BACKGROUND: Th2-type cytokines, such as IL-4 and IL-5, are generally believed to
      play an important role in the pathogenesis of allergic asthma. In contrast, Th1
      type cytokine, especially interferon (IFN)-gamma, is thought to have a
      downregulatory effect on Th2 immune response cells. Thus, the imbalance of Th1
      and Th2 cells may be a key factor in relation to disease severity. OBJECTIVE: The
      aim of this study is to examine the changes in the Th1/Th2 ratios and cytokine
      production profiles of asthmatic children at acute attacks and convalescent
      stages. METHODS: Twelve asthmatic patients were included in this study. The
      percentages of IFN-gamma- or IL-4-producing cells were determined with a flow
      cytometric method of intracellular protein detection. Fresh whole blood obtained
      from normal controls and patients at two stages was stimulated with brefeldin A,
      phorbol myristate acetate, and ionomycin for 4 hours. Cells were fixed and
      stained intracellularly with fluorescein isothiocyanate- or phycoerythrin
      conjugated antibody specific to each cytokine in combination with anti-CD4. ELISA
      assays were applied to measure cytokine concentrations of supernatant from
      peripheral blood mononuclear cells (PBMC) activated with phorbol myristate
      acetate and ionomycin for 24 hours. RESULTS: Among CD4+ cells, the percentage of
      IL-4+ cells decreased significantly from 8.18 +/- 4.77% at acute attacks to 4.18
      +/- 1.26% (P < .020) at convalescence. The percentage of IFN-gamma+ cells also
      decreased from 13.49 +/- 4.21% to 9.03 +/- 5.42% (P < .052). The Th1/Th2 ratios
      of patients at the two stages were similar, and both were lower than the normal
      controls. Significantly higher IL-5 and lower IFN-gamma production were detected
      from activated PBMC of asthmatic patients than normal controls. CONCLUSIONS: The
      decrease of IFN-gamma+ and IL-4+ cells detected at the single-cell level may
      explain the potential mechanism of convalescence from acute asthma attacks. High
      Th1/Th2 ratio and low IL-5 production from the PBMC of normal controls support
      the idea of a biased Th2 immune response in asthmatic patients.

PMID- 11289324
TI  - Airway responses to a diluent used in the methacholine challenge test.
AB  - BACKGROUND: Inhalation of diluent is often used in performing methacholine
      challenge tests, but its elimination has been suggested because marked falls in
      FEV1 after diluent inhalation have not been documented and performing this step
      is time-consuming. OBJECTIVE: We investigated the frequency and magnitude of
      response to the inhalation of diluent, and if there were any systematic effects
      in determining the PC20 using the baseline and postdiluent spirometric
      measurements. METHODS: All methacholine challenges performed during a 6-year
      period (N = 3,902) were reviewed retrospectively. RESULTS: The maximum increase
      and decrease in FEV1 and FVC from baseline were 56.3% and -41.4%, respectively,
      and 61.7% and -40.3%, respectively. The mean absolute changes from baseline in
      FEV1 and FVC were -0.018 L and -0.026 L, respectively. There was a highly
      significant correlation (r2 = 0.96; P < .0001) between the PC20 baseline and PC20
      postdiluent values, and a mean difference of 0.041 mg/mL (P < .0001), with the
      PC20 postdiluent being higher. CONCLUSIONS: These data do not provide strong
      evidence to support either using or eliminating the diluent stage. It is clear
      that there are frequent and sometimes large changes in FVC and FEV1 after the
      inhalation of diluent containing phenol and sodium bicarbonate buffer. If a
      laboratory intends to report changes in airway function qualitatively (ie,
      positive or negative), the diluent stage may not be necessary. However, if a
      laboratory intends to report bronchial challenge data from inhaling methacholine
      in a quantitative fashion and report a continuous variable such as PC20, a
      diluent stage is recommended.

PMID- 11289325
TI  - Nasal polyposis: a study of its association with airborne allergen
      hypersensitivity.
AB  - BACKGROUND: Despite the frequent presence of clinical symptoms such as sneezing
      and itching, elevated histamine and IgE in extracellular polyp fluids, tissue
      eosinophilia, and degranulated mast cells, allergy is not considered an important
      cause of nasal polyposis. OBJECTIVE: To investigate the prevalence of immediate
      skin reactivity to airborne allergens in patients with nasal polyposis. METHODS:
      Sixty-eight patients with nasal polyposis and 36 controls with chronic sinusitis
      were submitted to skin prick tests (SPTs) with a large series of seasonal and
      perennial airborne allergens including: grass, mugwort, ragweed, pellitory,
      plantain, birch, hazel, olive, cypress, house dust mites, cat and dog dander, and
      thirteen molds (Alternaria, Aspergillus, Cladosporium, Penicillium, Candida,
      Trichophyton, Fusarium, Curvularia, Botrytis, Pullularia, Rhizopus, Mucor,
      Helminthosporium). RESULTS: Forty-three of 68 (63%) patients with nasal polyposis
      versus 6 of 35 (17%) controls were positive on SPT with airborne allergens (P <
      .001). A comparison with 1,128 subjects with respiratory allergy seen from 1996
      to 1999 showed a markedly higher prevalence of sensitivity to Candida albicans
      (19 of 43 [44%] vs 8 of 1,128 [1%]; P < .001) and to house dust mites (12 of 43
      [28%] vs 154 of 1,128 [14%]; P < .05) among allergic patients with polyps.
      Altogether, 30 of 43 (70%) patients versus 215 of 1,128 (19%) controls were
      sensitive to at least one perennial airborne allergen (ie, mold, mite, or animal
      dander) on SPT (P < .001); in contrast, 26 of 43 (60%) patients versus 942 of
      1,128 (84%) controls were sensitive to seasonal airborne allergens (P < .005). A
      review of the clinical histories of SPT-positive patients revealed the presence
      of obstructive rhinitis and chronic rhinorrhea only in most cases, whereas acute
      symptoms, such as sneezing and itching, were reported only by a minority of
      subjects. CONCLUSIONS: A clinically slight respiratory allergy, particularly to
      perennial airborne allergens, might play a relevant role in the pathogenesis of
      nasal polyposis, probably through the induction of a long-lasting inflammation of
      the nasal mucosa.

PMID- 11289326
TI  - Onset of therapeutic effect of fluticasone propionate aqueous nasal spray.
AB  - BACKGROUND: The effectiveness of fluticasone propionate (FP) aqueous nasal spray
      in the treatment of rhinitis has been demonstrated in multiple controlled
      clinical studies. The onset of therapeutic effect of FP in these clinical trials
      appears to occur within 12 hours after administration of the initial dose.
      OBJECTIVE: This article presents an analysis from previous clinical trials that
      examined the efficacy of intranasal FP in patients with rhinitis to ascertain
      whether the time to onset of the therapeutic effect of this medication could be
      determined. METHODS: Completed randomized, double-blind, placebo-controlled
      studies with FP were evaluated to determine whether onset of effect could be
      evaluated based on the study designs. A study was deemed acceptable for
      evaluation of onset of effect if at least one evaluation of the intensity of
      nasal symptoms was completed within 12 hours after the initial dose of study
      medication and daily evaluations were made thereafter. Adult patients were
      included in the onset analysis if they received an initial FP dose of 200 microg.
      Pediatric patients who received an initial FP dose of 100 microg were also
      included. Onset of effect was evaluated by 1) examining the timepoints at which
      statistically significant differences were observed between FP and placebo in
      mean change from baseline for total nasal symptom score (TNSS); and by 2) using a
      binary probability model of success/failure to determine statistically
      significant differences from placebo. RESULTS: Twenty-two studies met the
      criteria to evaluate onset of therapeutic effect; 3,605 patients with rhinitis
      received FP and 2,271 patients received placebo. This database represents the
      largest compilation of data ever assembled to determine the onset of therapeutic
      effect of a corticosteroid nasal spray. Two studies used a "park design" to
      examine onset of effect; statistically significant differences in TNSS favoring
      FP were achieved at hours 2 to 4 and at hour 12, respectively. Using a binary
      probability model of success/failure for analysis of TNSS in the remaining 20
      studies not specifically designed to evaluate onset of effect, numerically
      greater improvements in TNSS for FP compared with placebo were found in 19 of the
      20 studies within 12 hours of the administration of the first dose (P < .001).
      Pairwise comparisons showed statistically significant improvement for TNSS within
      12 hours postdose in five of the studies for FP compared with placebo and in none
      for placebo compared with FP. CONCLUSIONS: Onset of therapeutic effect occurs
      within 12 hours, and as early as 2 to 4 hours in some patients, after
      administration of the first dose of FP aqueous nasal spray.

PMID- 11289327
TI  - Increased prevalence of asthma in Saudi Arabia.
AB  - BACKGROUND: Bronchial asthma is among the most common chronic illnesses of
      childhood. A number of reports in the recent past suggest that the prevalence of
      asthma is increasing globally. OBJECTIVE: To investigate the changing prevalence
      of asthma in the Kingdom of Saudi Arabia. SUBJECTS AND METHODS: Two populations
      of schoolchildren between the ages of 8 and 16 years were studied using an
      internationally designed protocol in 1986 and 1995. The questionnaire used in
      these studies was very similar to the one used in the International Study of
      Allergy and Asthma in Childhood. A total of 2,123 school-children in 1986 (Jeddah
      and Riyadh) and 1,008 schoolchildren in 1995 (Hail and Gizan) were enrolled in
      the surveys. These cross-sectional studies of randomly selected schoolchildren
      were statistically analyzed using ANOVA and a Z test. RESULTS: The comparison of
      data between Riyadh versus Hail (inland desert dry environment) and Jeddah versus
      Gizan (coastal humid environment) revealed that the prevalence of asthma in the
      similar populations increased significantly from 8% in 1986 to 23% in 1995 (P <
      .0001). Likewise, the prevalence of allergic rhinitis also increased from 20% to
      25% (P < .003) since 1986. However, no significant change in the prevalence of
      eczema (from 12% to 13%) was noted between 1986 and 1995. CONCLUSIONS: The study
      indicates that there was a significant increase in the prevalence of bronchial
      asthma and, to a lesser extent, in the prevalence of allergic rhinitis in the
      Kingdom of Saudi Arabia during this 9-year period. The study also revealed
      increased exposure to environmental factors such as tobacco smoke and indoor
      animals in Saudi houses. It seems that the continuing changes in contemporary
      life may well have contributed to the increased prevalence of asthma in the
      country.

PMID- 11289328
TI  - Switching from Ventolin CFC to Ventolin HFA is well tolerated and effective in
      patients with asthma.
AB  - BACKGROUND: Environmental imperatives to eliminate the use of chlorofluorocarbon
      (CFC) propellants in metered-dose inhalers have led to the development of metered
      dose inhalers with the hydrofluoroalkane (HFA-134a) propellants. OBJECTIVES: To
      evaluate the clinical effect of switching from Ventolin CFC to Ventolin HFA and
      to compare the efficacy and safety of Ventolin CFC, Ventolin HFA, and placebo in
      patients with asthma. METHODS: Multicenter, double-blind, randomized safety and
      efficacy trial comparing regular use of Ventolin CFC versus Ventolin HFA versus
      placebo for 12 weeks in 313 patients with asthma aged 12 years and older who
      received Ventolin CFC during a 3-week run-in period. RESULTS: Patients who were
      switched from Ventolin CFC to Ventolin HFA maintained pulmonary function and
      other measures of asthma control at levels comparable with run-in baseline.
      Serial pulmonary function testing demonstrated that both Ventolin treatments had
      significantly greater mean improvement in FEV1 over baseline than the placebo
      group at treatment day 1 and weeks 6 and 12 (P < .001). Both Ventolin groups had
      comparable pulmonary function at every visit. Predose FEV1 values were maintained
      or improved over time with all treatments. Treatments were well-tolerated. The
      adverse event profile for both Ventolin treatments was comparable with placebo.
      No clinically relevant effects on ECG, vital signs, or clinical laboratory tests
      were noted. Asthma exacerbation rates were 4% to 5% in the Ventolin groups and
      slightly higher (8%) in the placebo group. CONCLUSIONS: Patients who were
      switched from Ventolin CFC to Ventolin HFA maintained comparable asthma control
      with a similar safety profile.

PMID- 11289330
TI  - Variations in serum levels of interleukin (IL)-1beta, IL-2, IL-6, and tumor
      necrosis factor-alpha during specific immunotherapy.
AB  - BACKGROUND: Cytokine production by T helper cells is essential for the induction
      and maintenance of allergic inflammation in the bronchial mucosa. According to
      recent views, specific immunotherapy (SIT) favors the differentiation of T
      lymphocytes into cells of the Th1 rather than those of the Th2 subset. OBJECTIVE:
      To determine whether or not SIT induces a decrease in the inflammatory reaction
      by studying eventual variations in the serum levels of IL-1beta, IL-2, IL-6, and
      TNF-alpha in allergic subjects during SIT. METHODS: Serum levels of IL-1beta, IL
      2, IL-6, and TNF-alpha were determined before and after 3, 6, and 9 months of SIT
      by an immunoradiometric assay (IRMA) in 11 adults with perennial allergic asthma
      and/or rhinitis caused by house dust mites and in 6 nonatopic healthy volunteers.
      RESULTS: Median serum IL-1beta and TNF-alpha levels of the patients were
      significantly higher at baseline than those of the controls and decreased during
      SIT to values similar to or lower (P < .01) after 6 months of SIT for TNF-alpha
      than those of the controls. Median serum IL-2, significantly lower at baseline
      than in the controls, increased during SIT to a level similar to that of the
      controls. Although the median values of IL-1beta and TNF-alpha in the patients
      tended to decrease and those of IL-2 to increase during SIT, the differences were
      not significant; the correlation coefficients (r) of the serum levels of IL-1beta
      IL-6, and TNF-alpha versus duration of SIT were negative, while that of IL-2 was
      positive. CONCLUSIONS: Decreases in median serum IL-1beta and TNF-alpha levels
      during SIT, together with the increases in serum IL-2 and IL-6, compared with
      those of the controls furnish evidence supporting a reduction in the inflammatory
      response in the course of SIT.

PMID- 11289329
TI  - Correlation between airway hyperresponsiveness and airway inflammation in a young
      adult population: eosinophil, ECP, and cytokine levels in induced sputum.
AB  - BACKGROUND: Eosinophil counts and eosinophil cationic protein (ECP) levels in the
      airway are elevated in asthmatic patients. However, few studies have examined the
      correlation between various cytokines in the sputum and airway
      hyperresponsiveness (AHR) in young adults with or without asthma. OBJECTIVE: We
      examined the correlation between AHR and eosinophil counts or ECP, and levels of
      several cytokines in the sputum. METHODS: We studied 120 nonsmoker students
      (group 1: intermittent mild asthmatic patients; group 2: subjects with history of
      childhood asthma; group 3: subjects sensitized by Dermatophagoides farinae with
      atopic disease; group 4: normal subjects sensitized by D. farinae; group 5:
      subjects with cedar pollinosis; and group 6: normal subjects). In each subject,
      AHR and lung function tests were measured, together with eosinophil count, ECP,
      granulocyte-macrophage colony-stimulating factor, TNF-alpha, IL-5, and
      interleukin-1beta in induced sputum. RESULTS: AHR in groups 1 and group 2 were
      high, in groups 5 and 6 low, and in groups 3 and 4 lower than in groups 1 and 2
      but higher than groups 5 and 6. Percentages of eosinophils, ECP, and TNF-alpha in
      induced sputum in groups 1 and 2 were high, those in groups 5 and 6 were below
      detection limits, and those in groups 3 and 4 were lower than the percentages in
      groups 1 and 2. Granulocyte-macrophage colony-stimulating factor in the sputum
      was elevated only in group 1. The correlations between AHR and sputum eosinophil
      count, ECP, and TNF-alpha were significant, with the strongest correlation with
      TNF-alpha. CONCLUSIONS: Our results suggest that TNF-alpha levels in the sputum
      play an important role in determining the severity of AHR in young individuals.
      Further once AHR develops, it does not disappear, and the severity of airway
      inflammation influences the extent of AHR.

PMID- 11289331
TI  - Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children
      before and after a prednisolone course.
AB  - BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a
      role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role
      of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the
      disease activity of acute asthma, changes in serum concentrations of sIL-2R and
      IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy
      with clinical improvement were determined in the present study. METHODS:
      Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and
      in sera from 20 allergic asthmatic children with acute exacerbation and in a
      stable condition were determined by using commercially available ELISA kits.
      RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute
      exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2
      +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P <
      .001). The mean concentration of serum IL-4 was higher in acute exacerbation
      (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL)
      versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was
      not statistically significant among the three study groups. CONCLUSIONS: This
      study provides further evidence that changes in serum IL-2R may serve as an
      objective indicator for clinical outcome of allergic asthmatic patients.

PMID- 11289332
TI  - The effectiveness of high-dose inhaled budesonide therapy in the treatment of
      acute asthma exacerbations in children.
AB  - BACKGROUND: International guidelines recommend the use of systemic steroids for
      the treatment of acute asthma attack if it has not been resolved within 24 to 36
      hours of home management with regular beta2 mimetic inhalation. Such therapy for
      infrequent exacerbations is unlikely to have serious systemic effects.
      Unfortunately, many patients receiving frequent courses are potentially at risk
      for corticosteroid-induced side effects such as adrenal suppression, depression
      of linear growth, and osteoporosis. OBJECTIVE: To decrease the use of frequent
      oral corticosteroid courses in children, this study was designed to evaluate the
      efficacy of high-dose inhaled steroids in comparison with oral steroids, in the
      therapy of acute asthma exacerbations in children. METHODS: Sixty children who
      have experienced an acute exacerbation of asthma unresponsive to home management
      with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize,
      were randomized to be treated with either high-dose inhaled budesonide (1,600
      microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled
      budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000
      microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory
      volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced
      expiratory flow 25% to 75% (FEF25%-75%) were evaluated. RESULTS: The mean number
      of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose
      budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid
      receiving group (group II). There was a statistically significant difference
      between the two groups, in favor of group I (P = .038). No statistically
      significant difference was detected between the two groups with respect to the
      increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P =
      .790, .959, .819, respectively). CONCLUSIONS: Short-term high-dose budesonide
      therapy can be considered an alternative for children who are experiencing an
      acute asthma attack that is unresponsive to home management with regular use of
      an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.

PMID- 11289333
TI  - Significance of the eosinophil cationic protein/eosinophil count ratio in
      asthmatic patients: its relationship to disease severity.
AB  - BACKGROUND: Serum levels of eosinophil cationic protein (ECP) may reflect the
      degree of bronchial inflammation in patients with asthma, but its clinical value
      as a parameter for monitoring asthma remains controversial. OBJECTIVE: We
      measured the ratios of the serum ECP concentrations to peripheral blood
      eosinophil counts (ECP/Eo ratio) in patients with asthma and evaluated the
      correlation between these ratios and individual asthma severity. METHODS: The
      serum ECP concentrations and peripheral blood eosinophil counts were measured by
      radioimmunoassay and an autoanalyzer, respectively. Each patient with asthma was
      in remission at the time the serum specimen was obtained. An overall evaluation
      of asthma severity for each patient was determined by the frequency and severity
      of asthma attacks and by clinical scores. RESULTS: The ECP/Eo ratio in patients
      with severe asthma was significantly higher than in those with mild asthma.
      However, serum ECP concentrations and peripheral blood eosinophil counts were not
      different among the patients with mild, moderate, or severe asthma. The ECP/Eo
      ratios correlated significantly with the monthly average of the clinical scores,
      but the serum ECP concentrations did not correlate with the monthly average of
      the clinical scores. The ECP/Eo ratios were also increased in patients with more
      severe asthma whose serum IgE concentrations and peripheral eosinophil counts
      were not elevated. CONCLUSIONS: The ECP/Eo ratio may be useful in assessing
      asthma severity; however, the serum ECP concentration or peripheral blood
      eosinophil count is not useful.

PMID- 11289334
TI  - Severe serum sickness-like reaction to oral penicillin drugs: three case reports.
AB  - BACKGROUND: Because the use of heterologous sera has diminished, the incidence of
      serum sickness has declined. However, serum sickness-like reactions to nonprotein
      drugs continue to occur. METHODS: We report three cases of severe serum sickness
      like reactions in adults to oral penicillin drugs. RESULTS: In each patient,
      significant symptom resolution occurred within 24 hours of starting therapy with
      oral corticosteroids. CONCLUSIONS: Serum sickness-like reactions to oral
      penicillin drugs may be more common than reported in the literature and can be
      very severe. No specific laboratory finding is universally present or
      definitively diagnostic. As with classic serum sickness, the diagnosis of serum
      sickness-like reaction is made clinically. In severe cases such as those
      presented here with debilitating joint symptoms or life-threatening angioedema, a
      diagnostic-therapeutic trial of prednisone, 40 to 60 mg at least once daily, is
      warranted.

PMID- 11289335
TI  - Nonpigmenting solitary fixed drug eruption after skin testing and intra-articular
      injection of triamcinolone acetonide.
AB  - BACKGROUND: Although several medications have been reported to cause fixed drug
      eruption (FDE) reactions, triamcinolone acetonide has not been previously
      described as an offending agent. OBJECTIVE: To emphasize both an unprecedented
      causative agent and the extraordinary development of a FDE, we describe this
      response in a 42-year-old female patient. METHODS: Because her history included a
      questionable reaction to corticosteroid preparations, prick and intradermal
      testing with triamcinolone acetonide was done to determine whether she could
      safely receive a triamcinolone acetonide injection. RESULTS: Both skin test
      procedures and the intra-articular administration of triamcinolone acetonide
      caused FDEs on her right retroauricular area. CONCLUSIONS: Because any drug may
      induce a FDE by any administration route, physicians should be aware of this
      delayed skin reaction when skin testing drugs.

PMID- 11289336
TI  - Pollen-specific rush immunotherapy: clinical efficacy and effects on antibody
      concentrations.
AB  - BACKGROUND: Studies of rush immunotherapy (RIT) with standardized extracts for
      the treatment of seasonal pollen allergy are few, especially for birch-pollen
      RIT. OBJECTIVE: The study was performed to investigate the efficacy of RIT with
      standardized birch- or timothy-pollen extracts. Further, the serum antibody
      levels were evaluated for correlation with clinical efficacy. METHODS: This open,
      longitudinal study included 30 allergic patients treated with RIT and 16 allergic
      patients serving as a control group. The therapy was continued for 3 years and
      blood samples were collected at regular intervals for antibody measurements using
      the Pharmacia CAP System. RESULTS: The RIT was generally well tolerated. An
      increase in the total and specific IgE concentrations during the early months of
      RIT was observed, followed by decreased levels. Specific IgG and IgG4 increased
      continuously for 2 years. The symptom and medication scores were significantly
      decreased, compared with preRIT, at both the first and third pollen seasons after
      the start of RIT treatment (P < .0001 and P < .001, respectively). The clinical
      improvement during RIT was significantly greater compared with the control group
      (P < .05). The decreased medication and the symptom improvement during the third
      year of RIT correlated with the relative decrease in specific IgE (rs = .52, P <
      .05) and with the specific IgG4 level before the start of RIT (rs= -.68, P <
      .01), respectively. CONCLUSIONS: Our study indicates that RIT with standardized
      birch- or timothypollen extracts is clinically effective and safe. Measurements
      of specific antibody levels during treatment may be helpful in monitoring RIT.

PMID- 11289337
TI  - Asthma management and perceptions in rural South Africa.
AB  - BACKGROUND: Many First World countries have endeavored to measure the impact of
      asthma on individuals with asthma and, in addition to this quality of life
      evaluation, have attempted to define the quality of care for this common chronic
      illness. OBJECTIVE: The primary objective of this research probe was to assist
      the National Asthma Program in South Africa with the formulation and delivery of
      its outreach program to rural asthmatic patients. METHODS: A
      discussion/questionnaire document was compiled by Partners in Research from
      established literature. All interviews were conducted in either the clinics,
      hospitals, or respondents' homes. Both adult asthmatic patients and parents of
      pediatric asthmatic patients were interviewed. Interviewing took place at seven
      rural health clinics across South Africa. Each interview included extensive
      demographic details, questions on asthma definition, symptoms and symptom
      triggers, family history, age at diagnosis, frequency of symptoms, and treatment.
      RESULTS: Thirty-five adult asthmatic patients and 27 parents of pediatric
      asthmatic patients were interviewed. Of the adults, 40% reported wheezing at
      least once a week (despite diagnosis and treatment) and 19% of children reported
      similar symptom exacerbations. Fifty-one percent of adults and 56% of children
      were awakened at least once a week by cough or wheeze. Quality of life
      measurement reflected that, on average, 37% of responders were frightened during
      an acute asthma attack, and 68% of parents reported fearing the death of their
      asthmatic children. Fifty-one percent of adults and 33% of children had been
      hospitalized at least once for asthma. Although respondents claimed regular
      training in use of inhaler device, only 43% of adults completed each step
      correctly. CONCLUSIONS: There is a great deal of fear and ignorance surrounding
      asthma and, therefore, there is a real need for a greater level of patient
      education even in the rural areas of South Africa. In rural South Africa,
      attention should be paid to nurses, because they play a greater role than doctors
      in management and education of asthma.

PMID- 11289338
TI  - Red oak.

PMID- 11289339
TI  - Nicotine replacement for smokers.

PMID- 11289340
TI  - Long delays in seeking treatment for schizophrenia.

PMID- 11289341
TI  - Protein-Z and thrombosis.

PMID- 11289342
TI  - When stool cultures from adult inpatients are appropriate.

PMID- 11289343
TI  - Improvement in amblyopic eye function and contralateral eye disease: evidence of
      residual plasticity.

PMID- 11289344
TI  - Is reversal of chloroquine resistance ready for the clinic?

PMID- 11289345
TI  - Effect of fenofibrate on progression of coronary-artery disease in type 2
      diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study.
AB  - BACKGROUND: Atherosclerosis is the most common complication of diabetes.
      Correction of hyperglycaemia helps to prevent microvascular complications but has
      little effect on macrovascular disease. Post-hoc analyses of diabetic
      subpopulations in lipid intervention trials suggest that correction of
      lipoprotein abnormalities will lead to a decrease in coronary-artery disease. The
      Diabetes Atherosclerosis Intervention Study (DAIS) was specifically designed to
      assess the effects of correcting lipoprotein abnormalities on coronary
      atherosclerosis in type 2 diabetes. METHODS: 731 men and women with type 2
      diabetes were screened by metabolic and angiographic criteria. 418 were randomly
      assigned micronised fenofibrate (200 mg/day) or placebo for at least 3 years.
      They were in good glycaemic control (mean haemoglobin A1c 7.5%), had mild
      lipoprotein abnormalities, typical of type 2 diabetes, and at least one visible
      coronary lesion. Half had no previous clinical coronary disease. Initial and
      final angiograms followed a standard protocol and were analysed by a computer
      assisted quantitative approach. Missing data for the primary endpoints (minimum
      lumen diameter, mean segment diameter, and mean percentage stenosis) were
      imputed. Analyses were by intention to treat. FINDINGS: Total plasma cholesterol,
      HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations all changed
      significantly more from baseline in the fenofibrate group (n=207) than in the
      placebo group (n=211). The fenofibrate group showed a significantly smaller
      increase in percentage diameter stenosis than the placebo group (mean 2.11 [SE
      0.594] vs 3.65 [0.608]%, p=0.02), a significantly smaller decrease in minimum
      lumen diameter (-0.06 [0.016] vs -0.10 [0.016] mm, p=0.029), and a non
      significantly smaller decrease in mean segment diameter (-0.06 [0.017] vs -0.08
      [0.018] mm, p=0.171). The trial was not powered to examine clinical endpoints,
      but there were fewer in the fenofibrate group than the placebo group (38 vs 50).
      INTERPRETATION: DAIS suggests that treatment with fenofibrate reduces the
      angiographic progression of coronary-artery disease in type 2 diabetes. This
      effect is related, at least partly, to the correction of lipoprotein
      abnormalities, even those previously judged not to need treatment.

PMID- 11289346
TI  - Clinical picture: nail changes secondary to docetaxel.

PMID- 11289347
TI  - Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a
      multicentre randomised study.
AB  - BACKGROUND: Hydroxyethylstarch used for volume restoration in brain-dead kidney
      donors has been associated with impaired kidney function in the transplant
      recipients. We undertook a multicentre randomised study to assess the frequency
      of acute renal failure (ARF) in patients with severe sepsis or septic shock
      treated with hydroxyethylstarch or gelatin. METHODS: Adults with severe sepsis or
      septic shock were enrolled prospectively in three intensive-care units in France.
      They were randomly assigned 6% hydroxyethylstarch (200 kDa, 0.60-0.66
      substitution) or 3% fluid-modified gelatin. The primary endpoint was ARF (a two
      fold increase in serum creatinine from baseline or need for renal replacement
      therapy). Analyses were by intention to treat. FINDINGS: 129 patients were
      enrolled over 18 months. Severity of illness and serum creatinine (median 143
      [IQR 88-203] vs 114 [91-175] micromol/L) were similar at baseline in the
      hydroxyethylstarch and gelatin groups. The frequencies of ARF (27/65 [42%] vs
      15/64 [23%], p=0.028) and oliguria (35/62 [56%] vs 23/63 [37%], p=0.025) and the
      peak serum creatinine concentration (225 [130-339] vs 169 [106-273] micromol/L,
      p=0.04) were significantly higher in the hydroxyethylstarch group than in the
      gelatin group. In a multivariate analysis, risk factors for acute renal failure
      included mechanical ventilation (odds ratio 4.02 [95% CI 1.37-11.8], p=0.013) and
      use of hydroxyethylstarch (2.57 [1.13-5.83], p=0.026). INTERPRETATIONS: The use
      of this preparation of hydroxyethylstarch as a plasma-volume expander is an
      independent risk factor for ARF in patients with severe sepsis or septic shock.

PMID- 11289348
TI  - Changes in life expectancy in Russia in the mid-1990s.
AB  - BACKGROUND: Between 1987 and 1994, life expectancy in Russia declined
      substantially. Between 1994 and 1998, this trend reversed, and mortality rates
      returned to those of the early 1980s. Although the decline in life expectancy has
      been examined previously, much less is known about the subsequent improvement in
      mortality rates. We used recently published cause-specific mortality data up to
      1998 to clarify this issue. METHODS: Changes in cause-specific death rates at
      ages 15-74 years were examined. Rates for 1998 were compared with those for 1994
      (the year of lowest life expectancy) and for 1991 (the year the Soviet Union
      broke up). FINDINGS: Death rates among children fell steadily throughout the
      1990s, and those in elderly people changed little. The reduction in mortality
      since 1994 was mainly due to a decrease in the death rate among middle-aged
      adults, which had increased until 1994. Deaths among those aged 15-30 years,
      which rose during 1991-94, remained high. Some causes of death, such as stomach
      cancer and road-traffic accidents, declined throughout the 1990s, whereas others,
      such as breast and prostate cancers and tuberculosis, increased. The decline in
      mortality since 1994 was, however, mainly due to a reduction in the rate of
      deaths from a group of causes associated with alcohol consumption.
      INTERPRETATION: The changing life expectancy in Russia is a consequence of a
      complex pattern of trends in different causes of death, some of which have their
      origins long in the past, and others that result from contemporary circumstances.
      This study provides further support for the view that alcohol has played an
      important part in the fluctuations in life expectancy in Russia in the 1990s,
      although there remains a need for a much better understanding of the factors
      underlying these continuing changes.

PMID- 11289349
TI  - Low serum cholesterol and haemorrhagic stroke in men: Korea Medical Insurance
      Corporation Study.
AB  - BACKGROUND: In some prospective studies, haemorrhagic stroke occurs more
      frequently in individuals with low serum cholesterol than in those with higher
      concentrations. We aimed to determine whether low total serum cholesterol is an
      independent risk factor for haemorrhagic stroke (intracerebral haemorrhage and
      subarachnoid haemorrhage) in South Korea, a country that has a population with
      relatively low concentrations of total serum cholesterol. METHODS: We measured
      total serum cholesterol and other cardiovascular risk factors in 114,793 Korean
      men, aged between 35-59 years in 1990 and 1992, in a prospective observational
      study. We used data obtained in 1992 for smoking and alcohol consumption. We
      divided total serum cholesterol into quintiles (<4.31 mmol/L, 4.31-<4.74, 4.74
      <5.16, 5.16-<5.69 and > or = 5.69). Our primary outcomes were hospital admissions
      and deaths from intracerebral and subarachnoid haemorrhage in a 6 year follow-up
      between 1993 and 1998. FINDINGS: 528 men had a haemorrhagic stroke--372
      intracerebral and 98 subarachnoid haemorrhage--and 58 were unspecified strokes.
      The relative risks of intracerebral haemorrhage in each quintile of total serum
      cholesterol (lowest to highest were: 1.22 (95% CI 0.88-1.69); 0.86 (0.60-1.21);
      1.08 (0.78-1.48); and 1.03 (0.75-1.41). The corresponding relative risks for
      subarachnoid haemorrhage were: 1.44 (0.76-2.73); 1.13 (0.59-2.20); 1.21 (0.64
      2.29); and 1.12 (0.59-2.14). INTERPRETATION: Low total serum cholesterol is not
      an independent risk factor for either intracerebral or subarachnoid haemorrhagic
      stroke in Korean men.

PMID- 11289351
TI  - Headache and abdominal pain.

PMID- 11289350
TI  - Effect of topically applied T4 endonuclease V in liposomes on skin cancer in
      xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group.
AB  - BACKGROUND: In patients with xeroderma pigmentosum the frequency of all forms of
      skin cancer is higher than in the general population, owing to a genetic defect
      in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V, delivered
      intracellularly, increases the rate of repair of sunlight-induced DNA damage in
      human cells. We tested the ability of this enzyme in a liposomal delivery vehicle
      applied topically (T4N5 liposome lotion) to lower the rate of new skin cancers in
      patients with xeroderma pigmentosum. METHODS: 30 patients were enrolled in this
      prospective, multicentre, double-blind study. Patients were randomly assigned
      T4N5 liposome lotion or a placebo liposome lotion, to be applied daily for 1
      year. At 3-monthly visits, new actinic keratoses and basal-cell carcinomas were
      identified and removed. Analyses were by intention to treat. FINDINGS: 20
      patients were assigned T4N5 liposome lotion and ten placebo lotion; one placebo
      group patient withdrew before treatment and one withdrew with progressive disease
      at 9 months. The annualised rate of new actinic keratoses was 8.2 among the
      patients assigned T4N5 liposome lotion and 25.9 among those assigned placebo
      (difference 17.7 [95% CI 11.8-26.5]; p=0.004 by Poisson modelling). For basal
      cell carcinoma, the annualised rates of new lesions were 3.8 in the treatment
      group and 5.4 in the placebo group (difference 1.6 [0.38-2.82]). No significant
      adverse effects were found among any of the patients. INTERPRETATION: DNA damage
      has an important role in the development of skin cancer and precancerous skin
      lesions. The topical application of DNA repair enzymes to sun-damaged skin of
      patients with xeroderma pigmentosum lowered the rate of development of two forms
      of these lesions during a year of treatment.

PMID- 11289352
TI  - Sutureless mechanical anastomosis of a saphenous vein graft to a coronary artery
      with a new connector device.
AB  - Construction of vascular anastomoses by manual suturing is a highly skilled and
      time-consuming procedure. The St Jude Medical Anastomotic Technology Group has
      developed a sutureless mechanical anastomosis device, which, when tested in
      animals, produced anastomoses in less than 3 min and with little training. Here
      we present the results of the first clinical saphenous-vein to coronary-artery
      anastomosis by means of this device.

PMID- 11289353
TI  - Repopulation of liver endothelium by bone-marrow-derived cells.
AB  - The mechanism underlying the immunological advantage of hepatic allografts
      relative to other organs is incompletely understood. We used molecular probes for
      the repetitive units on the Y chromosome, to identify an increasing number of
      male liver venous endothelial cells in needle biopsy samples of men who received
      female donor liver grafts. We have also shown repopulation of liver endothelium
      by bone marrow derived cells in a male to female mouse bone marrow transplant
      model. We conclude that the liver has unique venous endothelium characterised by
      turnover and replacement by bone marrow derived cells.

PMID- 11289354
TI  - Frequency of protein Z deficiency in patients with ischaemic stroke.
AB  - Prothrombotic phenotype has been described in protein-Z deficient mice, but the
      thrombotic risk associated with protein Z deficiency in human beings is unknown.
      We saw a protein Z plasma concentration deficiency of about 20% in 169 patients,
      from two hospitals, who had ischaemic stroke, whereas the frequency in 88
      controls was about 5%. We saw no increase in the frequency of protein Z
      deficiency in 56 patients with venous thrombophilia. However, why protein Z
      deficiency was only observed in arterial thrombosis remains unknown.

PMID- 11289355
TI  - 20-fold increase in risk of lamivudine resistance in hepatitis B virus subtype
      adw.
AB  - We investigated subtype-dependent development of lamivudine resistance in
      hepatitis B virus (HBV) longitudinally in 26 consecutive patients (13 adw and 13
      ayw carriers) during antiviral treatment of chronic hepatitis B. Lamivudine
      resistance developed in seven adw carriers and one ayw carrier. Risk of
      lamivudine resistance was significantly higher for adw carriers than for ayw
      carriers (p=0.03). We believe that the adw subtype of HBV is associated with a
      high risk of lamivudine resistance, which might be linked to simultaneous changes
      of the HBsAg that occurs with the emergence of resistance.

PMID- 11289356
TI  - Matrix metalloproteinase-1 and skin ageing in smokers.
AB  - Smokers look older than non-smokers of the same age. We have compared the
      concentrations of mRNA for matrix metalloproteinase 1 (MMP-1) in the buttock skin
      of smokers and non-smokers with quantitative real-time polymerase chain
      reactions. MMP-1 degrades collagen, which accounts for at least 70% of the dry
      weight of dermis. We report significantly more MMP-1 mRNA in the skin of smokers
      than non-smokers whereas no difference was seen for the tissue inhibitor of
      metalloproteinases 1 (TIMP-1) or the housekeeping gene GAPDH (glyceraldehyde-3
      phosphate dehydrogenase). We suggest that smoking-induced MMP-1 might be
      important in the skin-ageing effects of tobacco smoking.

PMID- 11289357
TI  - UK investigators put forward theory for vCJD cluster.

PMID- 11289358
TI  - There's no pain without brain.

PMID- 11289360
TI  - Harsh criticism of Japan's treatment of death-row prisoners.

PMID- 11289359
TI  - DOTS--what's in a name?

PMID- 11289361
TI  - China opens drug market by revising pharmaceutical law.

PMID- 11289362
TI  - Political infighting causes Zimbabwe to dissolve AIDS council board.

PMID- 11289363
TI  - Future is bright for European drug market.

PMID- 11289364
TI  - Assessment of clinical competence.
AB  - Tests of clinical competence, which allow decisions to be made about medical
      qualification and fitness to practise, must be designed with respect to key
      issues including blueprinting, validity, reliability, and standard setting, as
      well as clarity about their formative or summative function. Multiple choice
      questions, essays, and oral examinations could be used to test factual recall and
      applied knowledge, but more sophisticated methods are needed to assess clincial
      performance, including directly observed long and short cases, objective
      structured clinical examinations, and the use of standardised patients. The goal
      of assessment in medical education remains the development of reliable
      measurements of student performance which, as well as having predictive value for
      subsequent clinical competence, also have a formative, educational role.

PMID- 11289365
TI  - Geographical differences in invasive pneumococcal disease rates and serotype
      frequency in young children.
AB  - The development of glycoconjugate vaccines for Streptococcus pneumoniae that are
      effective in very young children has renewed interest in identification of which
      among the more than 90 pneumococcal serotypes are most likely to cause invasive
      pneumococcal disease (IPD). Serotype distribution is thought to vary
      geographically, even between regions as socioeconomically similar as western
      Europe and North America. To explain these variations, we note the considerable
      variation that exists between reported rates of IPD in young children in the USA
      and west European countries. We postulate that this variation is attributable to
      different blood-culture rates and practices, and that mild IPD is probably
      underdiagnosed and under-reported in western Europe. On the basis of a comparison
      of serotype distributions between the two regions, we also postulate that those
      serotypes found at similar frequencies in both regions are virulent and rarely
      cause mild disease. As a result, reported distributions of IPD serotypes,
      especially when expressed as percentages, might be strongly skewed by the
      distribution of clinical presentations in a particular study population.

PMID- 11289366
TI  - Cautions over the current epidemic of primary aldosteronism.

PMID- 11289367
TI  - Hypobaric hypoxia.

PMID- 11289368
TI  - Hypobaric hypoxia.

PMID- 11289369
TI  - Hypobaric hypoxia.

PMID- 11289370
TI  - Fine-needle aspiration cytology of the thyroid in chronic fatigue.

PMID- 11289371
TI  - Transient global amnesia and disturbance of venous flow patterns.

PMID- 11289372
TI  - HIV-1 infection and risk of tuberculosis after rifampicin treatment.

PMID- 11289373
TI  - Prenatal detection of fetal Down's syndrome.

PMID- 11289374
TI  - Don't dismiss the floating kidney.

PMID- 11289375
TI  - Cholesterol-lowering therapy for smokers.

PMID- 11289376
TI  - Usefulness of dopamine treatment in non-oliguric renal failure.

PMID- 11289377
TI  - Cellular telephones and risk of brain tumours.

PMID- 11289378
TI  - Sunlight "D"ilemma.

PMID- 11289379
TI  - Clonal culture of fetal cells from maternal blood.

PMID- 11289380
TI  - The breaking of embargoes.

PMID- 11289381
TI  - Non-invasive prenatal diagnosis of Down's syndrome.

PMID- 11289382
TI  - Pennant's serpent.

PMID- 11289383
TI  - Nurturing wonder: the art of Nita Sturiale.

PMID- 11289384
TI  - Brain awareness on the web.

PMID- 11289385
TI  - Protest of Korean medical doctors against the government policy in 2000.

PMID- 11289386
TI  - Age-related regional difference of interleukin-1 expression in rat brain after
      lipopolysaccharide treatment.
AB  - Aging is associated with altered immune responses including dysregulation of
      cytokine production. Of cytokines, interleukin-1 (IL-1) family has been primarily
      involved with central nervous system. To evaluate the age-related different
      response of IL-1 family following peripheral administration of lipopolysaccharide
      (LPS), immunohistochemical study of IL-1beta and IL-1 receptor expression was
      performed on Sprague-Dawley rat brain. Experimental animals were divided into
      four groups; saline-treated young (3-5 months) and old (over 24 months), and LPS
      treated young and old groups. After intraperitoneal (i.p.) injection of LPS,
      three to five rats within each group were killed at 1, 2, 4, 8 and 16 hr. After
      fixation in 4% neutral buffered formalin, the brain slices were paraffin
      embedded. Immunohistochemical staining using labelled streptavidin biotin was
      performed. The results showed that IL-1beta immunoreactivity was seen in the
      endothelial cell of pons in both LPS-treated young and old rats, with slightly
      longer persistency in old group. IL-1RI immunoreactivity appeared initially in
      the neurons of cerebral cortex in LPS-treated old group, compared with
      predominantly the cerebellum in LPS-treated young group. In conclusion, our study
      shows that there is age-related, different neuronal localization of IL-1RI
      expression at different points of time after LPS treatment.

PMID- 11289387
TI  - A case of renal transitional cell carcinoma associated with synchronous
      contralateral renal cell carcinoma.
AB  - We report a case of simultaneous contralateral renal transitional cell carcinoma
      and renal cell carcinoma. A 63-yr-old male presented with hematuria. He was
      diagnosed with left renal pelvis tumor and contralateral renal cell carcinoma.
      Subsequently, the patient received left nephrectomy and paraaortic
      lymphadenectomy (transitional cell carcinoma, pT3N2M0). Post-operatively,
      chemotherapy of renal pelvis tumor and angioinfarction of contralateral renal
      cell carcinoma are being considered. We believe that management planning should
      be individualized in such cases.

PMID- 11289388
TI  - Left atrial myxosarcoma with systemic metastasis: a case report.
AB  - The term myxosarcoma is currently not used in standard classification for soft
      tissue tumors, but restricted to cardiac tumors. Primary cardiac myxosarcoma is a
      very rare disease and is difficult to differentiate from myxoma clinically and
      pathologically. We report a case of left atrial myxosarcoma with widespread
      systemic metastasis in a 21-yr-old male. The patient presented with sudden onset
      of intermittent dyspnea and orthopnea. Echocardiography showed a mobile,
      pedunculated tumor, 7.5x5x2 cm in size, at left atrium. Histologically, the
      excised tumor showed an amorphous finely fibrillar and mucinous stroma, in which
      irregular cords and clusters of lepidic cells and large stellate cells with plump
      vesicular nuclei resembled the usual type of cardiac myxoma were noted. And it
      showed focally cellular area with great nuclear pleomorphism and frequent
      mitoses. The patient received combination chemotherapy, peripheral blood stem
      cell collection transplantation and operations for systemic metastases in the
      brain, skeletal muscle and lung. He is alive at present 37 months after initial
      diagnosis and has no more new metastatic lesion.

PMID- 11289389
TI  - Spontaneous acute tumor lysis syndrome with advanced gastric cancer.
AB  - Acute tumor lysis syndrome (TLS) occurs frequently in hematologic malignancies
      such as high-grade lymphomas and acute leukemia, which are rapidly proliferating
      and chemosensitive tumors. It occurs rarely in solid tumors and has never been
      reported in gastric adenocarcinoma. Typical biochemical findings of acute tumor
      lysis syndrome are hyperuricemia, hyperkalemia, hyperphosphatemia and
      hypocalcemia in patients with a malignancy. Rapid changes of these electrolytes
      may cause cardiac arrhythmia, seizure, acute renal failure and sudden death.
      Therefore, as soon as it is detected, it should be taken care of immediately.
      Until now almost all cases of TLS associated with solid tumor have developed
      after cytoreductive therapy in chemosensitive tumors. We report here a case of
      spontaneous acute tumor lysis in a patient of advanced gastric cancer with
      hepatic metastases and multiple lymphadenopathy. The biochemical finding of TLS
      improved with the management and tumor burden also showed slight response to the
      one cycled combination chemotherapy but the patient died of progressive
      pneumonia.

PMID- 11289390
TI  - Laparoscopic-assisted resection of ileal lipoma causing ileo-ileo-colic
      intussusception.
AB  - Adult intussusception is rare, and the majority of cases has an underlying cause
      that requires surgical resection. We report a case of a 39 yr-old man with ileo
      ileo-colic intussusception caused by ileal lipoma that was successfully managed
      by a laparoscopic-assisted surgical maneuver. Using a three-cannula technique,
      ileo-colic intussusception was reduced laparoscopically. Then, through a 4-cm
      transverse incision in the right lower quadrant abdomen, ileo-ileal
      intussusception was reduced manually, and a resection of the tumor-bearing ileal
      segment and end-to-end anastomosis was performed extracorporeally. Although the
      role of laparoscopy in managing intussusception is not clearly defined,
      laparoscopy may be an alternative approach to the surgical treatment of adult
      intussusception in selected cases.

PMID- 11289391
TI  - Muellerianosis of the urinary bladder, endocervicosis type: a case report.
AB  - This case reports muellerianosis of the urinary bladder, showing glandular
      lesions made up of endocervical type glands, in a 36-yr-old woman. The patient
      presented with lower abdominal discomfort and pain on voiding. The patient had
      undergone two Cesarean sections 5 yr and 3 yr earlier. On a pelvic
      ultrasonography, a well-circumscribed mass, 2.2x0.8 cm in dimension, was found
      with luminal polypoid projection in the posterior wall of the urinary bladder.
      The patient had a transurethral resection of the bladder mass. Histologically,
      the tumor was composed of irregularly shaped glands lined by endocervical mucous
      epithelium in the muscularis propria of the urinary bladder. Some glands
      exhibited cystic dilatation and contained mucinous secretions. The glands
      elicited no desmoplastic tissue reaction. The intraluminal mucin often contained
      polymorphonuclear leukocytes. The glands were mostly lined by tall columnar and
      bland looking mucous cells with mucin secretion. The ciliated cells were rarely
      observed. No endometrial component is noted. It would be appropriate to designate
      this lesion as "Muellerianosis of the urinary bladder, endocervicosis type".
      Awareness of the lesion and attention to its typical histologic features should
      facilitate its crucial distinction from adenocarcinoma.

PMID- 11289392
TI  - Infantile hemangioendothelioma treated with high dose methylprednisolone pulse
      therapy.
AB  - Infantile hemangioendothelioma is a severe disease with a high mortality. It is
      characterized by multiple hemangioma affecting the skin and visceral organs. We
      report that high doses of methylprednisolone pulse therapy improved symptoms and
      signs of infantile hemangioendothelioma in a male neonate, and completely
      resolved the hepatic and cutaneous hemangioendothelioma on follow up.

PMID- 11289393
TI  - Kaposi's sarcoma occurring during short-term dialysis: report of two cases.
AB  - Kaposi's sarcoma (KS) appears to develop in association with kidney
      transplantation, but unlikely with dialysis. We report two cases of classic KS
      that occurred in patients receiving short-term (less than 3 yr) dialysis. They
      have been suffering from chronic renal failure due to tuberculosis and diabetes
      mellitus, respectively. Several to multiple, reddened-violaceous patches, plaques
      and nodules were found on the hand and the lower extremities. Laboratory studies
      showed no evidence suggesting immunosuppressed state and there was no history of
      taking immunosuppressive agents. The biopsies of the two cases revealed
      proliferation of spindle-shaped cells focally arranged in bundles and multiple
      dilated vascular spaces outlined by an attenuated endothelium with intravascular
      and extravasated erythrocytes. The specimens expressed positivity with CD34
      antigen. Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) was
      detected in one case by polymerase chain reaction method.

PMID- 11289394
TI  - Evaluation of serotyping using monoclonal antibodies and PCR-RFLP for Chlamydia
      trachomatis serotype identification.
AB  - We compared genotyping by restriction fragment length polymorphism (RFLP)
      analysis of the amplified omp1 gene with serotyping by dot enzyme-linked
      immunosorbent assay (dot-ELISA) to determine the suitability of RFLP analysis for
      epidemiologic study. Fifteen prototypes of Chlamydia trachomatis and 30 clinical
      isolates were used in this study. To serotype with dot-ELISA, chlamydia antigen
      was spotted onto a series of replicate nitrocellulose membrane patches and
      reacted with 11 mAbs that distinguish the 15 known serovars of C. trachomatis.
      For RFLP analysis, the amplified chlamydia omp1 gene was digested with AluI to
      differentiate serovars A to K and L1 to L3. Serovars of C, H, I, J, and L3 were
      further typed by RFLP analysis after digestion with HinfI, and a combination of
      EcoRI and DdeI. PCR-based RFLP could identify serotype of 28 among 30 clinical
      isolates tested. The remaining two untypical isolates were probably due to double
      infections or mechanical transferring error. Serotyping of C. trachomatis
      isolates shows that serovars E, D, F, and H are the most prevalent types found in
      urogenital samples in Korea. In this study, we show that RFLP analysis of
      amplified omp1 gene may be useful in genotyping C. trachomatis isolates.

PMID- 11289395
TI  - Meta-analysis of hypertension as a risk factor of cerebrovascular disorders in
      Koreans.
AB  - This study was conducted to integrate the results of previous studies which
      evaluated hypertension as a risk factor for cerebrovascular disorders (CVD) in
      Koreans. We retrieved the Korean literature using a manual search and the English
      literature using the MEDLINE database concerning the relationship between
      hypertension and CVD in Koreans from 1980 to 1997. The overall effect size of
      hypertension as a risk factor of CVD was represented by common odds ratio (OR).
      Before the integration of each effect size, a heterogeneity test and a
      sensitivity test was conducted. The materials were nine published epidemiologic
      studies with a total of 2,271 cases of CVD. The common ORs (95% confidence
      interval) of overall CVD, hemorrhagic CVD and ischemic CVD associated with
      hypertension were 4.10 (3.56-4.71), 6.56 (4.92-8.80) and 3.28 (2.77-3.90),
      respectively. Thus, the common OR of hemorrhagic CVD associated with hypertension
      was significantly higher than that of overall or ischemic CVD. This suggests that
      hypertension is an important risk factor for overall CVD and its subtypes in
      Koreans. Due to the lack of reliable prospective studies, however, longitudinal
      study is required in this area.

PMID- 11289396
TI  - Cell cycling status of human cord blood CD34+ cells during ex vivo expansion is
      related to the level of very late antigen expression.
AB  - Very late antigen-4 (VLA-4), which binds to the extracellular matrix protein
      fibronectin, is an integrin molecule known to be modulated during mobilization of
      CD34+ cells, and to be involved in signaling the mobilization stimuli. On the
      hypothesis that cell cycling status might be different depending on the level of
      VLA-4 expression, we investigated the DNA contents of human cord blood CD34+
      cells during ex vivo expansion by recombinant human thrombopoietin and flt3
      ligand with simultaneous measurement of surface VLA-4 at the 1st and 4th week.
      During this ex vivo expansion, expression of VLA-4 increased and almost all cells
      became VLA-4+ until the 4th day of culture. Expression of VLA-4 was maintained in
      the major population of the cultured cells until the 4th week. The cells in
      S/G2/M phase were greater in number in VLA-4 high fraction than in VLA-4 low
      fraction (n=4, p<.001). Furthermore, the fraction of cells in S/G2/M phase
      increased as the expression of VLA-4 became higher. These results suggest that
      cord blood CD34+ cells expressing high levels of VLA-4 have more proliferative
      activities.

PMID- 11289397
TI  - Sustained ventricular tachycardia in children after repair of congenital heart
      disease.
AB  - To investigate an association between surface electrocardiographic (ECG)
      parameters and sustained ventricular tachycardia (VT) in children after repair of
      congenital heart disease (CHD), data were obtained and analyzed in three groups
      (group I, 7 postoperative patients with episode of sustained VT (4 tetralogy of
      Fallot (TOF), 2 double outlet right ventricle (DORV), 1 truncus arteriosus);
      group II, 14 children with postoperative TOF not associated with VT; group III,
      14 normal children). Mean age at the onset of sustained VT was 129+/-77 months
      (range 60-232); mean age at corrective surgery, 44+/-33 months (range 10-102);
      mean follow-up period after surgery, 84+/-74 months (range 20-185); the duration
      from repair to the onset of sustained VT, range 1-185 months. Compared to group
      II and III, group I showed longer QRS duration (group I, 137+/-10 msec; group II,
      114+/-22 msec; group III, 65+/-12 msec) and shorter corrected J to Tmax interval
      (group I, 209+/-24 msec; group II, 272+/-44 msec; group III, 249+/-18 msec). QT
      and corrected QT, J to Tmax interval, and their dispersions in group I and II are
      significantly different from those of group III. In conclusion, QRS duration and
      corrected J to Tmax interval could be helpful to predict ventricular tachycardia
      in postoperative CHD.

PMID- 11289398
TI  - Influence of stent expansion states on platelet deposition in an extracorporeal
      porcine arteriovenous shunt model using a multichannel perfusion chamber.
AB  - Limited data are available about incomplete stent expansion (SE) on platelet
      deposition (PD). We examined PD following different SE using an extracorporeal
      porcine arteriovenous shunt model to which a perfusion chamber with four parallel
      silastic tubes were connected. Blood flow was set at a 20 and 100 mL/min in 1.8
      and 3.1 mm diameter tubes, respectively. P154 stents were deployed completely
      (Group A, n=15) or incompletely (Group B, n=15) in 1.8 mm (n=13) and 3.1 mm
      (n=17) tubes. 51Cr-labelled platelet autologous blood was injected 1 hr before
      the perfusion. After 15 min-perfusion, the testing tubes were assessed for
      radioactivity counts. In-stent cross sectional area was measured by intravascular
      ultrasound. There was a significant difference in PD between group A and B
      regardless of channel size (118+/-18.4 vs 261.4+/-52.1 pits x 10(6)/cm2, p<0.05).
      With adjusted shear rate and similar stenosis, PD was similar in both tubes. In
      smaller 1.8 mm tubes, a stenosis as subtle as 10% was associated with a
      significant PD difference (226.1+/-20 vs 112.9+/-20.5 plts x 10(6)/cm2, p<0.005).
      This model enabled a repetitive, simultaneous comparison of PD following
      different SE states. It seems that the quality of SE remains crucial in smaller
      channels.

PMID- 11289399
TI  - Enhanced neutrophil functions by recombinant human granulocyte colony-stimulating
      factor in diabetic patients with foot infections in vitro.
AB  - This study was performed to evaluate the effect of granulocyte-colony stimulating
      factor on neutrophil functions in diabetic patients with active foot infections
      in vitro. Twelve diabetic patients with foot infections and 12 normal volunteers
      were enrolled. Neutrophils from peripheral blood were incubated with granulocyte
      colony-stimulating factor (G-CSF, 50 ng/mL) for 20 min. Superoxide production of
      neutrophils was measured by the reduction of ferricytochrome C. Neutrophil
      phagocytosis was assayed using Staphylococcus aureus and the weighted phagocytic
      index was calculated. Superoxide production of neutrophils in diabetic patients
      with foot infections was 7.7 (unit: nmol/2 x 10(5) cells/60 min), which was
      significantly lower than that in controls (12.0) (p<0.05). G-CSF increased
      neutrophil superoxide production to 12.1 in diabetic patients with foot
      infections and to 19.8 in controls (p<0.05 for each). Weighted phagocytic index
      in diabetic patients with foot infections was 0.77, which was not significantly
      different from that of the controls (0.69). Weighted phagocytic index was
      increased significantly by G-CSF to 0.88 in diabetic patients with foot
      infections and to 0.79 in controls (p<0.05 for each). In conclusion, G-CSF
      significantly enhanced neutrophil functions in diabetic patients with foot
      infections in vitro.

PMID- 11289401
TI  - Changes in dead space/tidal volume ratio and pulmonary mechanics after surfactant
      replacement therapy in respiratory distress syndrome of the newborn infants.
AB  - This study was performed to elucidate the mechanism of improved oxygenation after
      surfactant replacement therapy in respiratory distress syndrome (RDS) of the
      newborn infants. In 26 newborns with RDS, end tidal-CO2 tension (PetCO2),
      arterial blood gas analysis and pulmonary function tests were measured at
      baseline, 30 min, 2 hr and 6 hr after surfactant administration. The changes in
      dead space/tidal volume ratio (VD/VT ratio=(PaCO2-PetCO2)/PaCO2), oxygenation
      index and arterial-alveolar partial pressure difference for oxygen ((A-a)DO2)
      were elucidated and correlated with pulmonary mechanics. Oxygenation index and (A
      a)DO2 improved, and VD/VT ratio decreased progressively after surfactant
      administration, becoming significantly different from the baseline at 30 min and
      thereafter with administration of surfactant. Pulmonary mechanics did not change
      significantly during the observation period. VD/VT ratio showed close correlation
      with OI and (A-a)DO2, but not with pulmonary mechanics. These results suggest
      that decreased physiologic dead space resulting from the recruitment of
      atelectatic alveoli rather than improvement in pulmonary mechanics is primarily
      responsible for the improved oxygenation after surfactant therapy in the RDS of
      newborn.

PMID- 11289400
TI  - Clinical significance of microvessel density in multiple myeloma patients.
AB  - To investigate the role of angiogenesis in multiple myeloma (MM), bone marrow
      biopsy from 75 adults with newly diagnosed, untreated MM were evaluated.
      Microvessels were scored in at least 3 areas ( x 200 fields) of the highest
      microvessel density in representative sections of each bone marrow specimen using
      immunohistochemistry for CD34. Prognostic variables were also evaluated for the
      overall survival. Microvessel counts were significantly higher in patients with
      MM (n=69.42+/-9.67), compared with control (n=26.81+/-2.85). Microvessel density
      had a weak correlation with percentage of bone marrow plasma cells. By univariate
      analysis, age, beta2-microglobulin, serum albumin, serum creatinine, serum
      calcium, hemoglobin, platelet count, and bone marrow plasma cell percentage were
      correlated with survival. By multivariate analysis, age, serum albumin, serum
      creatinine, hemoglobin, platelet count and bone marrow plasma cell percentage
      were correlated with overall survival, whereas microvessel density was not. In
      summary, microvessel density in bone marrow of MM is significantly increased
      compared to control, but was not correlated with overall survival. Further
      studies regarding angiogeneic molecules are needed to determine the functional
      role of angiogenesis in MM.

PMID- 11289402
TI  - Diverse profiles of specific IgE response to toluene diisocyanate (TDI)-human
      serum albumin conjugate in TDI-induced asthma patients.
AB  - The prevalence studies on specific IgE to toluene diisocyanate (TDI)-human serum
      albumin (HSA) conjugate in TDI-induced asthma have shown variable results. In
      this study, we attempted to compare specific IgE bindings to TDI-HSA conjugate
      and its specificity using 3 different conjugates. Sera were collected from 20 TDI
      induced asthma and 10 controls. Specific IgE were measured by ELISA using three
      TDI-HSA conjugates; two from Carnegie Mellon (CM; 98 and 99 CM conjugates) and
      one from Ajou University. To evaluate specificity and cross-reactivity, ELISA
      inhibition tests were applied. Positive and negative predictive values between
      Ajou conjugate and 98 CM conjugate were 75% and 100%. Those between Ajou and 99
      CM were 100% and 93.8%. One patient showed an isolated positive response to the
      Ajou with negative responses to the other two conjugates. ELISA inhibition test
      using this patient's serum revealed the significant inhibitions by the Ajou and
      minimal inhibitions by the others. On the other hand, another patient showed an
      isolated positive response to 99 CM with negative responses to the others, and
      ELISA inhibition test showed significant inhibition by 99 CM with minimal
      inhibitions by the others. These results suggest that specific IgE bindings to a
      new antigenic determinant of TDI-HSA conjugate can be heterogeneous and differ
      from one individual to another.

PMID- 11289403
TI  - Expression of MAGE-1, -2, and -3 genes in gastric carcinomas and cancer cell
      lines derived from Korean patients.
AB  - We investigated the expression of MAGE-1, -2, and -3 genes in tissues of 51
      gastric carcinomas from Korean patients and in 11 gastric cancer cell lines
      established in Korea using reverse transcriptase-polymerase chain reaction along
      with immunohistochemical analyses and DNA sequencing. Among the 51 gastric
      carcinomas, MAGE-1, -2, and -3 genes were expressed in 16 (31%), 22 (43%), and 17
      (33%), respectively, and 31 (60%) expressed at least one of the three genes. In
      contrast, none of the three MAGE genes were expressed in normal sites of gastric
      tissue from each cancer patient. Out of 11 gastric cancer cell lines, MAGE-1, -2,
      and -3 genes were expressed in two (18%), five (46%), and four (36%),
      respectively. According to the clinicopathological analysis, the expression of
      any of the three MAGE genes was not significantly correlated with several
      clinicopathological factors except histologic types (p= 0.067).
      Immunohistochemical analyses identified positive staining with monoclonal
      antibodies 77B and 57B specifically against MAGE-1 and -3 proteins, respectively,
      in nuclei and cytoplasms of cells in mRNA-positive tumor tissue. These findings
      suggest the possibility as a target for tumor-specific immunotherapy for Korean
      patients.

PMID- 11289404
TI  - Combination of oxaliplatin, fluorouracil, and leucovorin in the treatment of
      fluoropyrimidine-pretreated patients with metastatic colorectal cancer.
AB  - There has been no standard therapy for patients with metastatic colorectal cancer
      who have failed to first-line fluorouracil-based treatment. The present study was
      designed to assess the efficacy and toxicities of a combination of oxaliplatin, 5
      fluorouracil (5-FU) and leucovorin in fluoropyrimidine-pretreated patients with
      metastatic colorectal cancer. Chemotherapy consisted of oxaliplatin 85 mg/m2 on
      day 1, followed by leucovorin 20 mg/m2 and 5-FU 1,200 mg/m2 on days 1 and 2.
      Treatment courses were repeated every two weeks. Thirty-nine patients were
      enrolled in this study. All patients previously received fluoropyrimidine-based
      chemotherapy. Thirty-one patients were assessable for response and 33 for
      treatment toxicity. Six patients required dose reduction of 5-FU due to grade
      III/IV cytopenia. Nausea/vomiting and peripheral neuropathy were common non
      hematologic toxicities. Overall response rate was 42.0% including 3 complete
      response and 10 partial response. The median response duration was 91 days
      (range, 28-224+). The median duration of progression-free survival was 132 days
      (range, 40-308). A combination of oxaliplatin, 5-FU, and leucovorin showed high
      response rate in fluoropyrimidine-pretreated patients with metastatic colorectal
      cancer, but the duration of response was relatively short. It may be worthwhile
      to explore its therapeutic potential in the first-line treatment setting.

PMID- 11289405
TI  - Altered remodeling of nucleolar machineries in cultured hepatocytes treated with
      thioacetamide.
AB  - Thioacetamide (TA) is converted into a hyperacetylating agent which causes
      hepatic necrosis, regeneration, cirrhosis and cancerous transformation. One of
      the most characteristic toxicities of TA in rat is observed with a 50 mg/kg per
      day which induces nucleolar enlargement different from that in regenerating
      liver. From TA-treated liver, the nucleoli were isolated and characterized for an
      altered nucleolar signal transduction system. Immunochemistry revealed that the
      poisoned nucleoli had increased levels of both nucleolus specific proteins
      (nucleophosmin and nucleolin) and various signal molecules (CK2, Erk1/2, p38,
      protein kinases A and C, and cyclin A). Using flow cytometry, the nucleoli were
      found to be in G2-arrested nuclei. Manifestation of the nucleolar enlargement
      could be readily observed using an ex vivo hepatocyte culture. There were two
      types of nucleolar enlargement. One was observed in normal hepatocytes with light
      density of enlarged nucleoli. The other was in TA-treated hepatocytes with dense
      and compact density of enlarged nucleoli, which contained a 3 to 5-fold higher
      nudeophosmin content than the control. In vitro induction of nucleolar
      enlargement with TA was possible. As soon as the hepatocytes anchored on a
      collagen coat, exogeneous TA (higher than 1 microg/mL) could induce dense and
      compact nucleoli. However, when an exogeneous drug was added after monolayer
      formation (1 day), no drug-induced nucleolar enlargement was observed.

PMID- 11289406
TI  - Correlation of VEGF with contrast enhancement on dual-phase dynamic helical CT in
      liver tumors: preliminary study.
AB  - The purpose of this preliminary study is to elucidate that vascular endothelial
      growth factor (VEGF) influences contrast enhancement of hepatic tumors on
      computed tomography (CT). Fourteen patients with hepatic tumors (11
      hepatocellular carcinomas; 3 metastatic cancers) underwent a dual-phase dynamic
      helical CT or computed tomographic hepatic arteriography. The attenuation of each
      mass was determined as hyperattenuation, isoattenuation or hypoattenuation with
      respect to the adjacent nontumorous parenchyma. Gun-needle biopsy was done for
      each tumor, and paraffin sections were immunostained with anti- VEGF antibody by
      the avidin-biotin-peroxidase complex method. The pathologic grade was made by
      intensity (1 +, 2+, 3+) and area (+/-, 1 +, 2+). The tumor ranged 2.0-14.0 cm in
      size (mean, 5.8 cm). In arterial phase, the intensity was not correlated with the
      degree of enhancement (p=0.086). However, the correlation between the attenuation
      value of hepatic arterial phase and the area of positive tumor cells was
      statistically significant (p=0.002). VEGF may be the factor that enhances the
      hepatic mass with water-soluble iodinated contrast agent in CT.

PMID- 11289407
TI  - Schizophrenic delusions in Seoul, Shanghai and Taipei: a transcultural study.
AB  - In this transcultural study of schizophrenic delusions among patients in Seoul,
      Shanghai and Taipei, we discovered that both the frequency and content of
      delusions differed among the three groups; and that these differences could
      perhaps be explained by varying sociocultural and political situations.
      Delusional themes that are sensitive to sociocultural or political situations
      include guilt, love/sex, religion, somatic damage, economy/business and politics.
      Delusions regarding longevity, love/sex, dysmorphophobia/dysosmophobia, religion
      or supernatural matters, and espionage/spy stories were most frequent in Seoul
      patients. Those in Taipei predominantly had delusions about possession, religion
      or supernatural matters, hypnotism, and mass media/computers. Shanghai patients
      often had delusions of poisons, being prickled by poisoned needles, their brain
      and viscera extracted and being a family member of political authorities.

PMID- 11289408
TI  - Transplacental transfer and age-related levels of serum IgG antibodies to the
      capsular polysaccharides of Streptococcus pneumoniae types 14 and 19 in Korea.
AB  - Little is known about the prevalence of naturally acquired IgG antibodies to the
      capsular polysaccharides of Streptococcus pneumoniae (pneumococcal IgG) in Korea.
      In the present study, we investigated transplacental transfer and age-related
      levels of pneumococcal IgG to provide background seroepidemiologic data for S.
      pneumoniae in Korea. One hundred thirty eight sera were assayed by ELISA for IgG
      to pneumococcal polysaccharide capsular serotypes 14 and 19, the predominant
      serotypes for under 15 yr of age in Korea. The subjects were divided into 7
      subgroups according to age. The cord/maternal geometric mean titer of
      pneumococcal were 4.47+/-5.88/5.21 +/- 5.88 for serotype 14, and 4.68 +/-
      5.55/6.55 +/- 6.92 for serotype 1 9 (mean +/- standard deviation, microg/mL).
      After birth, the geometric mean titers of pneumococcal IgG for serotypes 14 and
      19 expressed in microg/mL were 1.18+/-2.12 and 1.41+/-2.17 in the 0-6 months
      group, 0.27+/-0.19 and 0.69+/-0.93 in 7-12 months, 0.21+/-0.22 and 0.64+/-1.32 in
      1-2 yr, 0.69+/-0.78 and 2.65+/-2.46 in 3-6 yr, 2.52+/-2.72 and 8.29+/-4.24 in 7
      10 yr, respectively. In conclusion, reduced transplacental transfer and very low
      serum concentrations of pneumococcal IgG may contribute to the susceptibility of
      neonates, infants, and young children to S. pneumoniae infection.

PMID- 11289409
TI  - Incidence and clinical profile of extra-medial-temporal epilepsy with hippocampal
      atrophy.
AB  - We tried to investigate the incidence and the clinical profile of intractable
      epilepsy with hippocampal atrophy and ictal onset zones located in areas other
      than the hippocampus (extra-medial-temporal epilepsy; EMTE). We included patients
      who had hippocampal atrophy confirmed by MRI but with extra-medial-temporal ictal
      onset zones as verified by invasive intracranial electrodes or video-EEG
      monitoring. The case histories, interictal EEG, ictal semiology, other MRI
      findings in addition to hippocampal atrophy, and results of ictal SPECT and PET
      scans were evaluated. Results were compared with those of surgically proven
      medial temporal lobe epilepsy with hippocampal atrophy recruited during the same
      period. 8.5% of the intractable epilepsy patients with hippocampal atrophy had
      extra-medial temporal epileptogenic zones. A history of encephalitis and
      hemiconvulsion-hemiparesis were significantly common in the EMTE group. Most of
      the interictal EEGs of EMTE patients showed extratemporal irritative zones. MRI,
      ictal SPECT, and FDG-PET seemed to be helpful at localizing the true
      epileptogenic zones. The predominant EMTE seizure type was focal motor seizure
      with secondary generalization. Some portion of intractable epilepsy patients with
      hippocampal atrophy had extra-medial-temporal epileptogenic foci and careful
      analysis of semiology and neuroimagings could yield clues to correct diagnosis.

PMID- 11289410
TI  - A readout scheme providing high spatial resolution for distributed fluorescent
      sensors on optical fibers.
AB  - Optical fiber sensors using fluorescent probes distributed along the fiber
      cladding are of great interest for monitoring physical and chemical properties in
      their environment. The location of an emitting fluorophore along a fiber can be
      determined by measuring the time delay between a short, exciting laser pulse
      propagating in the fiber core and the returning fluorescence pulse. However,
      fluorescence lifetimes limit the spatial resolution, since a minimum separation
      of the fluorophores is required to resolve returning light pulses. For many
      applications, a closer spacing of sensor regions is desirable. We present a new
      method for the readout of closely packed fluorescent chemosensors located in the
      cladding of an optical fiber. By using a second fiber as an optical delay line,
      the minimum spacing between adjacent sensor regions can be well below the
      fluorescence lifetime limit. Since the coupling between the two fibers is
      evanescent, the attenuation of the excitation pulse is low, making long arrays of
      sensor regions feasible. This is particularly important since the one-dimensional
      combinatorial chemistry method developed by us allows for efficient preparation
      of diverse linear arrays. Detection sensitivities of 10(-7) mol/L are
      demonstrated, with the potential for significant improvement.

PMID- 11289411
TI  - Localization of analyte molecules in MALDI preparations by confocal laser
      scanning microscopy.
AB  - In this study, the incorporation of Texas Red-labeled avidin into crystals of 2,5
      dihydroxybenzoic acid (2,5-DHB) and 2,6-DHB (used as matrixes for matrix-assisted
      laser desorption/ionization (MALDI)) was investigated by fluorescence
      spectrophotometry and confocal laser scanning microscopy (CLSM). The analyte
      distribution in crystals, grown slowly under controlled conditions, was compared
      to the analyte localization in different standard preparations (dried-droplet and
      thin-layer preparation). Texas Red turned out to be a useful fluorescence label
      in the acidic environments of typical matrixes. Earlier results by absorption
      spectrophotometry could be confirmed by fluorescence measurements; 2,5-DHB
      incorporates the analyte proportionally, while 2,6-DHB excludes the protein from
      its crystal lattice. It is found that the analyte distribution can be analyzed
      well in both single crystals and standard preparation, by CLSM using Texas Red
      labeled analytes. The present study allows for a conclusive and consistent
      interpretation of analyte incorporation into MALDI preparations.

PMID- 11289412
TI  - Automated single-particle SEM/EDX analysis of submicrometer particles down to 0.1
      microm.
AB  - Typically single-particle SEM/EDX analysis of aerosols is done on polycarbonate
      filters or solid carbon substrates. This has led to a widespread conclusion that
      EDX provides poor information on carbon, oxygen, and nitrogen content of a
      particle and usually could not go below 0.5-microm particles. We show that use of
      grid-supported carbon films of 15-25-nm thickness gives exceptionally low
      background in the SEM/EDX analysis and allows satisfied automated analysis of
      particles down to 0.1-microm size, including detection of low-Z elements. In this
      work, six laboratory-generated 0.1-2-microm aerosols were tested for their
      elemental composition. The EDX analysis yields reasonably accurate quantitative
      results featuring all the elements present in the tested compounds, namely, C, O,
      N, Na, S, Al, Si, and Cl. Furthermore, the carbon film has very low backscattered
      electron (BSE) yield compared to that from the particle, so in the BSE mode the
      particle image is seen with very high contrast. This greatly improves quality and
      speed of the automated mapping of particles by SEM prior to EDX analysis.

PMID- 11289413
TI  - Solid-phase microextraction-mass spectrometry: a new approach to the rapid
      characterization of cheeses.
AB  - This work describes a new method for the rapid characterization of cheeses by
      solid-phase microextraction coupled with mass spectrometry (SPME-MS). After four
      types of fiber were tested and the main extraction parameters studied, the
      volatile components were extracted using a Carboxen/PDMS 75-microm fiber placed
      for 10 min at 20 degrees C in the headspace of the cheese. The substances
      adsorbed were then transferred directly from the injector to the inlet of a mass
      spectrometer through a 1-m deactivated silica capillary column heated to 210
      degrees C. The mass spectra thus obtained without prior chromatographic
      separation formed a "fingerprint" of the analyzed sample. For data analysis, the
      mass fragments of each spectrum (45 < m/z < 150 amu) were considered as potential
      descriptors of the composition of the headspace of the cheeses. Stepwise
      discriminant analysis was used to select a limited number of mass fragments that
      afforded an operational classification of the batches of cheeses studied. This
      new method offers the advantage of minimizing thermal, mechanical, and chemical
      modifications of the matrix, thereby reducing the risk of analytical artifacts.
      SPME-MS provides a simple and effective approach to rapid quality control by
      analysis of the volatile fraction of foods.

PMID- 11289414
TI  - Self-referencing ceramic-based multisite microelectrodes for the detection and
      elimination of interferences from the measurement of L-glutamate and other
      analytes.
AB  - A self-referencing technique utilizing two microelectrodes on a ceramic-based
      multisite array is employed for confirmation and elimination of interferences
      detected by enzyme-based microelectrodes. The measurement of L-glutamate using
      glutamate oxidase was the test system; however, other oxidase enzymes such as
      glucose oxidase can be employed. One recording site was coated with Nafion with L
      glutamate oxidase and bovine serum albumin (BSA) cross-linked with glutaraldehyde
      while the other had Nafion with BSA cross-linked with glutaraldehyde. Differences
      in the chemistry of the two recording sites allowed for identification and
      elimination of interfering signals to be removed from the analyte response. The
      electrode showed low detection limits (LOD = 0.98 +/- 0.09 microM, signal-to
      noise ratio of 3), fast response times (T90 approximately 1 s), and excellent
      linearity (R2 = 0.999 +/- 0.000) over the concentration range of 0-200 microM for
      calibrations of L-glutamate in vitro. The selectivity and dimensions of the
      multisite electrode allow in vivo glutamate measurements. This electrode has been
      applied to in vivo measurements of the clearance of locally applied glutamate and
      release of glutamate in the prefrontal cortex of anesthetized rats. In addition,
      a aimilar approach has been applied to the development of a microelectrode for
      measures of glucose.

PMID- 11289415
TI  - Development of a microchamber array for picoliter PCR.
AB  - A microchamber array for PCR was developed by semiconductor microfabrication
      technology. The microchambers were designed to be of picoliter quantity. To
      optimize fluid retention, the surface states of the substrate and the inner walls
      were examine for four different types of microchamber. The substrate was silicon,
      while silicon dioxide was selected for the inner walls. PCR was performed in the
      microchamber array, and the amplification of DNA was detected using a technique
      based on the energy transfer of fluorescent dyes. The lower volume limit for PCR
      was investigated using various sizes of microchambers. Microchambers with volume
      greater than 86 pL gave successful PCR. In addition, the system was improved in
      order to take up the PCR product. To prevent mixing of the samples, the samples
      were dried after PCR using a membrane that permeates only vapor.

PMID- 11289417
TI  - Fluoro reactants and dual luminophore referencing: a technique to optically
      measure amines.
AB  - An optical sensor for aqueous 1-butylamine is presented which combines two novel
      techniques: A fluorescent indicator dye (fluoro reactand) embedded in a thin
      polymer layer performs a reversible chemical reaction with the analyte, causing
      changes in luminescence intensity. At the same time, inert phosphorescent beads
      dispersed within the polymer layer provide luminescence signals that act as an
      internal reference for the indicator dye. As a consequence, the optical sensor is
      independent of light source fluctuations, ambient light, drifts in optoelectronic
      setup, or optical fiber bending.

PMID- 11289416
TI  - A method for the fabrication of low-noise carbon fiber nanoelectrodes.
AB  - A new and facile method has been developed for the fabrication of low-noise
      carbon fiber microelectrodes (CFMEs) and carbon fiber nanoelectrodes (CFNEs). The
      carbon fiber was flame-fuse sealed in the tip of the glass capillary. The CFMEs
      were made by cutting the protruding carbon fiber to the desired length, and the
      CFNEs were achieved by etching the protruding carbon on the flame to form a
      nanometer-scale tip. The tip of CFNEs can be controlled within the range from 100
      to 300 nm. Thus, no epoxy wax was involved in the CFMEs and CFNEs. The
      experimental results of inspecting CFMEs and CFNEs by scanning electron
      microscopy demonstrated that the surface of the electrodes and the glass/fiber
      interface are very smooth. Therefore, the noise caused by the glass/fiber of
      these electrodes is much lower than that of the electrodes fabricated
      conventionlly. The electrodes were characterized by ferricyanide, catecholamine
      (dopamine,DA), norepinephrine (NE), and epinephrine (E)) and 5-hydroxytryptamine
      (5-HT) neurotransmitters using CV, LSV, DPV, and FSCV. The results showed that
      the CFMEs and CFNEs have very excellent electrochemical behavior and high
      sensitivity. The CV and DPV detection limits of DA, NE, and E are 7.6 x 10(-8),
      7.0 x 10(-8), and 5.0 x 10(-8) mol/L, and the DPV detection limits of DA, NE, and
      E are 4.0 x 10(-8), 1.0 x 10(-7), and 2.2 x 10(-7) mol/L, respectively. This
      experiment offers a new and facile method for the fabrication of CFMEs and CFNEs
      of very high sensitivity and low noise.

PMID- 11289418
TI  - Fluorescent liposome flow markers for microscale particle-image velocimetry.
AB  - Unilamellar liposomes carrying both encapsulated and surface-immobilized
      fluorophores have been synthesized as novel fluorescent markers to image flow
      profiles in microfabricated structures. The unilamellar liposomes were made with
      phospholipids and cholesterol by extrusion through a polycarbonate membrane. They
      contained carboxyfluorescein in the aqueous core and fluorescein-labeled lipids
      in the bilayer to render them both a surface and volume fluorescer, maximizing
      their fluorescence intensity. The lipid composition was chosen to impart a net
      negative charge to liposomes to minimize self-aggregation as well as interaction
      with negatively charged glass surfaces of the channels. These liposomes were
      monodisperse (mean diameter 283 nm), neutrally buoyant, and hydrophilic and
      exhibited no adsorption on glass surfaces. Unlike polystyrene spheres, they were
      readily broken up by surfactants, thereby allowing for easy and complete removal
      from microfluidic channels. The fluorescent liposomes were used to investigate
      pressure-driven flow in an offset cross intersection in a microfluidic chip and
      provided images with excellent signal-to-noise ratio. A novel computational
      scheme that is particularly suitable for analyzing particle-image velocimeby data
      in micrometer-scale flow channels was employed to anabze the images. These
      liposomes are easily synthesized and can be custom-made for various applications
      to offer a broad range of surface and volume characteristics such as charge,
      size, and surface chemistry.

PMID- 11289419
TI  - Near-infrared spectrometric determination of di- and tripeptides synthesized by a
      combinatorial solid-phase method.
AB  - A new method based on near-infrared (NIR) spectrometry and partial least-squares
      analysis has been developed for the noninvasive and nondestructive determination
      of the identity and sequences of amino acid residues in di- and tripeptides. The
      di- and tripeptides were synthesized from six amino acids with similar structures
      (Gly, Ala, Leu, Met, Phe, Val) on two different polymer beads (bead with and
      without a linker) using the solid-phase peptide synthetic method. The developed
      NIR method is capable of determining the identity of sequences of these di- and
      tripeptides (with and without the Fmoc protecting group) directly on the polymer
      beads. It can distinguish not only dipeptides from tripeptides but also peptides
      with very similar structures (e.g., bead-Gly-Ala-Ala, bead-Gly-Ala-Phe, bead-Gly
      Ala-Leu, bead-Gly-Ala-Val, and bead-Gly-Ala-Met). More importantly, the method is
      capable of distinguishing di- and tripeptides with the same amino acid residues
      but different sequences (e.g., bead-Gly-Leu-Val from bead-Gly-Val-Leu).

PMID- 11289421
TI  - Stacking extra-long samples in capillaries.

PMID- 11289420
TI  - Analytical chemistry and the life sciences.

PMID- 11289422
TI  - Tunable deep blue light for laser spectrochemistry.

PMID- 11289423
TI  - Molecular micelles: novel pseudostationary phases for CE.

PMID- 11289425
TI  - High-resolution NMR gets even better.

PMID- 11289424
TI  - Centennial retrospective on chemical sensors.

PMID- 11289426
TI  - What did one cell say to the other?

PMID- 11289427
TI  - Conduct-as-cast polymer monoliths as separation media for capillary
      electrochromatography.
AB  - We have developed porous polymer monoliths (PPMs) that are versatile and robust
      reversed-phase chromatography media. The PPMs are cast-to-shape, UV-cured
      polymers that form uniform packings within pretreated glass capillaries and fused
      silica chips. No applied pressure is ever needed to flush the PPMs since they
      support electroosmotic flow as cast. Such characteristics make the PPMs useful
      for chip-based devices. Our results show efficiencies greater than or equal to
      150,000 plates/m for both capillary and chip-based separations of polycyclic
      aromatic hydrocarbons. By changing the monomers, the hydrophobicity of the
      polymers, and the direction of the electroosmotic flow can be altered without
      degrading chromatographic performance. We describe here the development of these
      acrylate-based materials along with both physical and chromatographic
      characterization.

PMID- 11289428
TI  - Concentration jump experiments for the precise determination of rate constants of
      reverse reactions in the millisecond time range.
AB  - Low dissociation or reverse rate constants of single-step or multistep complex
      formation equilibria are usually obtained with reduced precision from standard
      stopped-flow binding experiments by determination of the intercept of the
      concentration dependence of k(obs). Large and fast concentration jumps, based on
      two different step-motor-driven mixing setups, are performed with 60-300-fold
      dilutions that allow the precise, convenient, and independent determination of
      dissociation rate constants in the range of approximately 0.1-100 s(-1) in a
      single stopped-flow dissociation experiment. A theoretical basis is developed for
      the design and for the evaluation of such dilution experiments by considering the
      rebinding occurring during dissociation. The kinetics of three chemical systems
      are investigated, the binding of Mg2+ to 8-hydroxyquinoline as well as of Ca2+
      and K+ to the cryptand [2.2.2], by carrying out standard stopped-flow binding as
      well as dissociation experiments employing various dilution factors. The
      advantage of the dilution method for investigating chemical and biological
      systems is emphasized.

PMID- 11289429
TI  - Time-of-flight mass spectrometric analysis of high-molecular-weight alkanes in
      crude oil by silver nitrate chemical ionization after laser desorption.
AB  - Time-of-flight mass spectrometry was used for the first time to analyze the
      hydrocarbons in crude oil. Alkanes in the saturated fraction of a crude oil
      sample were chemically ionized by the laser desorption of silver nitrate, and the
      silver-attached C24-C60 alkanes were resolved with mass accuracy below 7 ppm.
      This technique was used to evaluate the biodegradation of aliphatic hydrocarbons
      and cycloalkanes by oil-degrading microorganisms resident in seawater. It is
      shown that the aliphatic hydrocarbons were degraded in the range of 60-80%, while
      the mono-, di-, tri-, tetra-, and pentacycloalkanes were degraded in the range of
      40-55, 20-30, 10-16, 5-9, and <5%, respectively. Its high sensitivity and speed
      of application could result in an analysis by laser desorption silver chemical
      ionization time-of-flight mass spectrometry being the method of choice for
      determining high-molecular-weight hydrocarbons in various petroleum products.

PMID- 11289430
TI  - 2D electrochemical time of flight and its application in the measurements of the
      kinetics of lateral electron hopping in monolayer films at the air/water
      interface.
AB  - A 2D electrochemical time-of-flight (ETOF) method was developed to measure
      diffusion constants of lateral mobility of amphiphiles and lateral electron
      hopping in Langmuir monolayers at the air/water interface. Photolithographically
      fabricated generator-collector ETOF devices featured two parallel gold
      microelectrodes (7 mm in length, 40 microm wide, spaced by a 10-microm gap). In
      2D ETOF measurements, such a device is touching the water surface where the
      generator and collector electrodes function as a collinear pair of line
      microelectrodes. Bulk measurements, with a generator-collector device submerged
      in an electrolyte solution, were carried out to calibrate the devices by relating
      the transit times to the known D values of Ru(NH3)6(2+) in a series of solutions
      of different viscosity adjusted with sucrose. A new method to define and to
      measure transit times in the step mode ETOF experiments was developed that
      requires only the pseudo-steady-state values of the collector current.
      Reliability of the 2D ETOF technique was established by investigating lateral
      diffusion of an amphiphilic tetradecane TEMPO derivative for which the D values
      were also measured by 2D voltammetry. Combination of 2D ETOF and 2D voltammetry
      allows one to independently measure diffusion coefficients and concentrations of
      redox species. This advantageous feature was then used to reevaluate kinetics of
      lateral electron hopping in Os(DPP)3(ClO4)2 (DPP, 4,7-diphenyl-1,10
      phenanthroline) solid monolayers on the water surface. The true rate constant of
      electron self-exchange, kex = 1.0 x 10(9) M(-1) s(-1), was obtained. The fact
      that the latter is more than 1 order of magnitude larger than its value obtained
      in a homogeneous acetonitrile solution suggests that the structure and locale of
      the Os(DPP)3(III+/II+) monolayer system result in a larger electronic coupling
      and/or smaller reorganization energy.

PMID- 11289431
TI  - Scanning tunneling microscopy with chemically modified tips: discrimination of
      porphyrin centers based on metal coordination and hydrogen bond interactions.
AB  - STM gold tips chemically modified with 4-mercaptopyridine (4MP) were found
      capable of discriminating zinc(II) 5,15-bis(4-octadecyloxyphenyl)porphyrin (Por
      Zn) from its metal-free porphyrin (Por-2H) and nickel(II) complexes (Por-Ni) in
      the mixed monolayers of these compounds, spontaneously formed at the
      solution/graphite interface. The porphyrin centers in STM images observed with
      4MP-modified tips exhibited bright spots, while those measured with unmodified
      tips exhibited the porphyrin centers as dark depressions. The centers of Por-Zn
      were brighter than those of Por-2H and Por-Ni, thereby allowing the
      discrimination of Por-Zn from Por-2H or Por-Ni in mixed monolayers. The changes
      in the contrasts of porphyrin centers of Por-2H and Por-Zn/ Por-Ni were explained
      by facilitated electron tunneling due to hydrogen bond and metal coordination
      interactions, respectively, between porphyrin centers and the pyridyl group of
      4MP on the tip.

PMID- 11289432
TI  - Detection and classification characteristics of arrays of carbon black/organic
      polymer composite chemiresistive vapor detectors for the nerve agent simulants
      dimethylmethylphosphonate and diisopropylmethylphosponate.
AB  - Arrays of conducting polymer composite vapor detectors have been evaluated for
      performance in the presence of the nerve agent simulants
      dimethylmethylphosphonate (DMMP) and diisopropylmethylphosponate (DIMP). Limits
      of detection for DMMP on unoptimized carbon black/ organic polymer composite
      vapor detectors in laboratory air were estimated to be 0.047-0.24 mg m(-3). These
      values are lower than the EC50 value (where EC50 is the airborne concentration
      sufficient to induce severe effects in 50% of those exposed for 30 min) for the
      nerve agents sarin (methylphosphonofluoridic acid, 1-methylethyl ester) and soman
      (methylphosphonofluoridic acid, 1,2,2-trimethylpropyl ester), which has been
      established as approximately 0.8 mg m(-3). Arrays of these vapor detectors were
      easily able to resolve signatures due to exposures to DMMP from those due to DIMP
      or due to a variety of other test analytes (including water, methanol, benzene,
      toluene, diesel fuel, lighter fluid, vinegar, and tetrahydrofuran) in a
      laboratory air background. In addition, DMMP at 27 mg m(-3) could be detected and
      differentiated from the signatures of the other test analytes in the presence of
      backgrounds of potential interferences, including water, methanol, benzene,
      toluene, diesel fuel, lighter fluid, vinegar, and tetrahydrofuran, even when
      these interferents were present in much higher concentrations than that of the
      DMMP or DIMP being detected.

PMID- 11289433
TI  - Electroanalytical performance of carbon films with near-atomic flatness.
AB  - Physicochemical and electrochemical characterization of carbon films obtained by
      pyrolyzing a commercially available photoresist has been performed. Photoresist
      spin-coated on to a silicon wafer was pyrolyzed at 1,000 degrees C in a reducing
      atmosphere (95% nitrogen and 5% hydrogen) to produce conducting carbon films. The
      pyrolyzed photoresist films (PPF) show unusual surface properties compared to
      other carbon electrodes. The surfaces are nearly atomically smooth with a root
      mean-square roughness of <0.5 nm. PPF have a very low background current and
      oxygen/carbon atomic ratio compared to conventional glassy carbon and show
      relatively weak adsorption of methylene blue and anthraquinone-2,6-disulfonate.
      The low oxygen/carbon ratio and the relative stability of PPF indicate that
      surfaces may be partially hydrogen terminated. The pyrolyzed films were compared
      to glassy carbon (GC) heat treated under the same conditions as pyrolysis to
      evaluate the electroanalytical utility of PPF. Heterogeneous electron-transfer
      kinetics of various redox systems were evaluated. For Ru(NH3)6(3+/2+), Fe(CN)6(3
      /4-), and chlorpromazine, fresh PPF surfaces show electron-transfer rates similar
      to those on GC, but for redox systems such as Fe3+/2+, ascorbic acid, dopamine,
      and oxygen, the kinetics on PPF are slower. Very weak interactions between the
      PPF surface and these redox systems lead to their slow electron-transfer
      kinetics. Electrochemical anodization results in a simultaneous increase in
      background current, adsorption, and electron-transfer kinetics. The PPF surfaces
      can be chemically modified via diazonium ion reduction to yield a covalently
      attached monolayer. Such a modification could help in the preparation of low
      cost, high-volume analyte-specific electrodes for diverse electroanalytical
      applications. Overall, pyrolysis of the photoresist yields an electrode surface
      with properties similar to a very smooth version of glassy carbon, with some
      important differences in surface chemistry.

PMID- 11289435
TI  - Diamond optically transparent electrodes: demonstration of concept with
      ferri/ferrocyanide and methyl viologen.
AB  - A new type of optically transparent electrode is reported on--an electrically
      conductive diamond thin film. The electrode was free-standing (0.38 mm thick and
      8 mm in diameter), mechanically polished to a 7-nm rms roughness over a 10-microm
      linear distance, boron-doped (0.05% B/C in the reactant gas mixture), and mounted
      in a thinlayer transmission cell. The electrode has a short-wavelength cutoff of
      approximately 225 nm, which is the indirect band gap of the material, and
      transmits light out to at least 1,000 nm. In theory, the electrode has an optical
      window from 225 nm well out into the far-infrared, except for the boron acceptor
      band and the intrinsic multiphonon absorptions. The electrode was used to
      electrooxidize ferrocyanide to ferricyanide, and the absorbance change associated
      with the formation of the oxidized product (lambdamax = 420 nm) was
      spectroscopically monitored. The electrode was also used to electroreduce methyl
      viologen (MV2+) to the cation radical (MV+*) and the neutral (MV0). The depletion
      of MV2+ (lambdamax = 257 nm) and formation of MV+* (lambdama = 398 and 605 nm)
      were spectroscopically monitored.

PMID- 11289434
TI  - Development of an electrochemical immunosensor for direct detection of interferon
      gamma at the attomolar level.
AB  - An electrochemical immunosensor for direct detection of the 15.5-kDa protein
      interferon-gamma (IFN-gamma) at attomolar level has been developed. Self
      assembled monolayers (SAMs) of cysteine or acetylcysteine are formed on
      electropolished polycrystalline Au electrodes. IFN-gamma adsorbs physically to
      each of these SAMs. With injections of 100 mM KCl, IFN-gamma can be removed in
      the flow without damaging the acetylcysteine SAM. However, the cysteine SAM is
      affected by these KCl injections. In an on-line procedure in the flow, a specific
      antibody (MD-2) against IFN-gamma is covalently attached following
      carbodiimide/succinimide activation of the SAM. The activation of the carboxylic
      groups, attachment of MD-2, and deactivation of the remaining succinimide groups
      with ethanolamine are monitored impedimetrically at a frequency of 113 Hz, a
      potential of +0.2 V versus SCE, and an ac modulation amplitude of 10 mV. Plots of
      the real (Z') and imaginary (Z") component of the impedance versus time provide
      the information to control these processes. In the thermostated setup (23.0
      degrees C), samples of unlabeled IFN-gamma (in phosphate buffer pH 7.4) are
      injected and the binding with immobilized MD-2 is monitored with ac impedance or
      potential-step methods. While the chronoamperometric results are rather poor, the
      ac impedance approach provides unsurpassed detection limits, as low as 0.02 fg mL
      1 (approximately 1 aM) IFN-gamma. From a calibration curve (i.e. Z" versus the
      amount injected), recorded by multiple 50-microL injections of 2 pg mL(-1) of IFN
      gamma, a dynamic range of 0-12 pg mL(-1) could be derived. However, when
      nonspecific adsorption is taken into account, which has been found to be largely
      reduced through injections of 100 mM KCl, a much smaller dynamic range of 0-0.14
      fg mL(-1) remains. The immunosensor can be regenerated by using a sequence of
      potential pulses in the flow by which the SAM with attached MD-2 and bound IFN
      gamma is completely removed. When the developed procedures described above are
      repeated, the response of the immunosensor is reproducible within 10%.

PMID- 11289436
TI  - Investigation of the electrochemical and electrocatalytic behavior of single-wall
      carbon nanotube film on a glassy carbon electrode.
AB  - The electrochemical behavior of a film of single-wall carbon nanotubes (SWNTs)
      functionalized with carboxylic acid groups was studied extensively on a glassy
      carbon (GC) electrode. One stable couple corresponding to the redox of the
      carboxylic acid group, which was supported by XPS and IR experiments, was
      observed. The electrode process involved four electrons, while the rate
      determining step was a one-electron reduction. The SWNT film-modified electrode
      showed favorable electrocatalytic behavior toward the oxidation of biomolecules
      such as dopamine, epinephrine, and ascorbic acid.

PMID- 11289437
TI  - Redox and double-layer charging of phenothiazine functionalized monolayer
      protected clusters.
AB  - Monolayer-protected Au clusters (MPCs) have been prepared with mixed monolayers
      of alkanethiolates and alkanethiolates terminally omega-functionalized with
      phenothiazine. The mixed monolayer MPCs can contain as many as 10
      phenothiazines/MPC; these electron donors are electroactive in rapid, successive
      one-electron reactions. Surface adsorption of the functionalized MPCs is evident
      in cyclic voltammetry. Double-potential-step chronocoulometry with incremented
      potential steps was applied to unfunctionalized hexanethiolate-coated MPCs and to
      those functionalized with phenothiazine to analyze the coupling between the
      diffusion-controlled double-layer charging of the MPC cores and the oxidation of
      the phenothiazine centers. Apparent changes in ordering of the MPC alkanethiolate
      chains were observed with infrared spectroscopy in solutions of MPCs where
      alcohol, carboxylic acid, or phenothiazine moieties had been incorporated into
      the monolayer.

PMID- 11289438
TI  - A positionable microcell for electrochemistry and scanning electrochemical
      microscopy in subnanoliter volumes.
AB  - Positionable voltammetric cells with tip diameters of < 50 microm were
      constructed from theta glass capillaries. One channel of the pulled glass
      capillary contains a carbon fiber microelectrode sealed in epoxy while the other
      houses a Ag/AgCl reference electrode that makes electrical contact to the analyte
      solution via a salt bridge at the tip. The device can be operated as a two
      electrode cell and can therefore make measurements in droplets of solution that
      are similar in size to the tip. Alternatively, if the droplet of solution is
      larger than the tip, spatially resolved measurements of a substrate in solution
      can be made. Voltammetric experiments and feedback imaging with the scanning
      electrochemical microscope (SECM) were accomplished in microdroplets with
      solution volumes of less than 1 nL. pH images of a substrate immersed in 70
      microL-thick films of solution were obtained in the generator-collector mode of
      SECM using an iridium oxide-modified microcell. This type of microcell is
      particularly useful for making electrochemical measurements in very small
      droplets of solution where a mobile working electrode could easily collide with a
      separately positioned reference electrode.

PMID- 11289439
TI  - Intramolecular fluorescence resonance energy transfer system with coumarin donor
      included in beta-cyclodextrin.
AB  - In aqueous solutions, the fluorescence of the intramolecular fluorescence
      resonance energy-transfer (FRET) system 1 was strongly quenched, because of close
      contact between the donor and acceptor moieties. FRET occurred, and the acceptor
      fluorescence was increased, by adding beta-cyclodextrin (beta-CD) to aqueous
      solutions of 1. Spectral analysis supported the idea that the FRET enhancement
      was due to the formation of an inclusion complex of the coumarin moiety in beta
      CD, resulting in separation of the fluorophores. On the basis of this result, we
      propose that covalent binding of coumarin to beta-CD will provide a FRET cassette
      molecule. So, compound 2 bearing beta-CD covalently was designed and synthesized.
      Fluorescence intensity of 2 was enhanced markedly compared to the intensity of 3.
      Applying this FRET system, various FRET probes that will be useful for ratio
      imaging and also the high-throughput screening will be provided.

PMID- 11289440
TI  - Phase-sensitive fluorescence lifetime detection in capillary electrophoresis.
AB  - A simple and highly sensitive fluorescence lifetime detection method for
      capillary electrophoresis has been introduced. The detection scheme is based on
      the integrated phase-sensitive fluorescence intensity. The integrative nature of
      the method results in high sensitivity of lifetime detection. The limit of
      detection is 7.8 amol of fluorescein injected, representing a 2 orders of
      magnitude improvement over the detection limits previously reported in the UV
      visible region. Rayleigh scattering, Raman scattering, and background
      fluorescence can be effectively suppressed by setting the detector out of the
      phase from the background signal. Fluorescence background can be eliminated
      whether the fluorescence lifetime of the background is longer or shorter than the
      solute molecules of interest. The signal-to-noise ratio of measurements is
      optimized by varying the modulation frequency and the detector phase angle.

PMID- 11289441
TI  - High-performance liquid chromatography interfaced with fluorescence line
      narrowing spectroscopy for on-line analysis.
AB  - We have demonstrated, for the first time, that high-performance liquid
      chromatography (HPLC) can be interfaced with fluorescence line-narrowing
      spectroscopy (FLNS) for on-line identification and characterization of analytes.
      Interfacing centered primarily on the design and construction of a novel liquid
      helium cryostat that accommodates variable-sized quartz tubes/capillaries
      suitable for HPLC as well as capillary electrophoresis/electrochromatography. In
      addition to the high spectral resolution afforded by FLNS, analyzing the
      separated components at 4.2 K minimizes photodegradation from the excitation
      source and provides indefinite detection times for signal averaging. The proof-of
      principle for the HPLC-FLNS system is first demonstrated with a mixture of four
      structurally similar polycyclic aromatic hydrocarbons and then applied to the
      analysis of DNA adducts from mouse skin exposed to the carcinogen
      dibenzo[a,l]pyrene. With femtomole detection limits, HPLC-FLNS can be used for
      real-world analyses of complex mixtures.

PMID- 11289442
TI  - An optical method for the detection of oxidative stress using protein-RNA
      interaction.
AB  - The cytosolic 4Fe-4S protein aconitase can be converted under the influence of
      reactive oxygen species into an iron-regulatory protein (IRP1). Therefore, the
      IRP1 level is considered as an indirect marker of oxidative stress. An
      experimental approach is presented here to detect the concentration of this
      marker protein by surface plasmon resonance. The optical method exploits the
      natural binding affinity of IRP1 to an iron-responsive element (IRE) which was in
      vitro transcribed with a linker sequence and subsequently immobilized on a
      BIACORE sensor chip. The detection was found to be reproducible and sensitive in
      the range 20-200 nM IRP. Conditions of the binding process, such as pH and thiol
      concentration, were characterized. Feasibility of the method to detect and
      quantify IRP1 in physiological media was demonstrated.

PMID- 11289443
TI  - Single bead characterization using analytical constructs: application to quality
      control of libraries.
AB  - Analytical construct technology has been successfully applied to the single-bead
      analysis of a split-mix combinatorial library. Substrates can be released from
      the resin by conventional cleavage for biological screening. Alternatively, for
      the purpose of analysis and quality control, cleavage at an orthogonal construct
      linker produces an analytical fragment incorporating the substrate. This
      analytical fragmnent is highly sensitized to electrospray mass spectrometry (ESI
      MS) and is easily identified by isotope labeling. The construct cleavage rendered
      readily visible even those compounds that clearly could not be seen by
      conventional cleavage and mass spectrometry analysis. A 1H NMR control experiment
      proved that the compounds cleaved conventionally were, however, present in the
      sample in good yield and purity. In view of the data obtained, we think that this
      is a significant and important step toward solving our current quality control
      problems.

PMID- 11289444
TI  - Analysis of a GC/MS thermal desorption system with simultaneous sniffing for
      determination of off-odor compounds and VOCs in fumes formed during extrusion
      coating of low-density polyethylene.
AB  - A thermal desorption equipment introducing volatile organic compounds (VOCs) into
      the gas chromatographic/ mass spectrometric system (GC/MS) with simultaneous
      sniffing (SNIFF) is a suitable method for identifying the volatile organic off
      odor compounds formed during the extrusion coating process of low-density
      polyethylene. Fumes emitted during the extrusion coating process of three
      different plastic materials were collected at two different temperatures (285 and
      315 degrees C) from an outgoing pipe and near an extruder. The VOCs of fumes were
      analyzed by drawing a known volume of air through the adsorbent tube filled with
      a solid adsorbent (Tenax GR). The air samples were analyzed by using a special
      thermal desorption device and GC/MS determination. The simultaneous sniffing was
      carried out to detect off-odors and to assist in the identification of those
      compounds that contribute to tainting and smelling. The amounts of off-odor
      carbonyl compounds and the total content of the volatile organic compounds were
      determined. The most odorous compounds were identified as carboxylic acids while
      the majority of the volatile compounds were hydrocarbons. The detection and
      quantification of carboxylic acids were based on the characteristic ions of their
      mass spectra. The higher the extrusion temperature the more odors were detected.
      An important observation was that the total concentration of volatiles was
      dependent not only on the extrusion temperature but also on the plastic material.

PMID- 11289445
TI  - Quantitative proteomic analysis using a MALDI quadrupole time-of-flight mass
      spectrometer.
AB  - We describe an approach to the quantitative analysis of complex protein mixtures
      using a MALDI quadrupole time-of-flight (MALDI QqTOF) mass spectrometer and
      isotope coded affinity tag reagents (Gygi, S. P.; et al. Nat. Biotechnol. 1999,
      17, 994-9.). Proteins in mixtures are first labeled on cysteinyl residues using
      an isotope coded affinity tag reagent, the proteins are enzymatically digested,
      and the labeled peptides are purified using a multidimensional separation
      procedure, with the last step being the elution of the labeled peptides from a
      microcapillary reversed-phase liquid chromatography column directly onto a MALDI
      sample target. After addition of matrix, the sample spots are analyzed using a
      MALDI QqTOF mass spectrometer, by first obtaining a mass spectrum of the peptides
      in each sample spot in order to quantify the ratio of abundance of pairs of
      isotopically tagged peptides, followed by tandem mass spectrometric analysis to
      ascertain the sequence of selected peptides for protein identification. The
      effectiveness of this approach is demonstrated in the quantification and
      identification of peptides from a control mixture of proteins of known relative
      concentrations and also in the comparative analysis of protein expression in
      Saccharomyces cerevisiae grown on two different carbon sources.

PMID- 11289446
TI  - Sol-gel open tubular ODS columns with reversed electroosmotic flow for capillary
      electrochromatography.
AB  - Sol-gel chemistry was successfully used for the fabrication of open tubular
      columns with surface-bonded octadecylsilane (ODS) stationary-phase coating for
      capillary electrochromatography (OT-CEC). Following column preparations, a series
      of experiments were performed to investigate the performance of the sol-gel
      coated ODS columns in OT-CEC. The incorporation of N-octadecyldimethyl[3
      (trimethoxysilyl)propyl]ammonium chloride as one of the sol-gel precursors played
      an important role in the electrochromatographic performance of the prepared
      columns. This chemical reagent possesses a chromatographically favorable, bonded
      ODS moiety, in conjunction with three methoxy groups allowing for sol-gel
      reactivity. In addition, a positively charged nitrogen atom is present in the
      molecular structure of this reagent and provides a positively charged capillary
      surface responsible for the reversed electroosmotic flow (EOF) in the columns
      during CEC operation. Comparative studies involving the EOF within such sol-gel
      ODS coated and uncoated capillaries were performed using acetonitrile and
      methanol as the organic modifiers in the mobile phase. The use of a deactivating
      reagent, phenyldimethylsilane, in the sol-gel solution was evaluated. Efficiency
      values of over 400,000 theoretical plates per meter were achieved in CEC on a 64
      cm x 25 microm i.d. sol-gel ODS open tubular column. Test mixtures of polycyclic
      aromatic hydrocarbons, benzene derivatives, and aromatic aldehydes and ketones
      were used to evaluate the CEC performances of both nondeactivated and deactivated
      open tubular sol-gel columns. The effects of mobile-phase organic modifier
      contents and pH on EOF in such columns were evaluated. The prepared sol-gel ODS
      columns are characterized by switchable electroosmotic flow. A pH value of
      approximately 8.5 was found correspond to the isoelectric point for the prepared
      sol-gel ODS coatings.

PMID- 11289447
TI  - Determination of carbamate, urea, and thiourea pesticides and herbicides in
      water.
AB  - Microbore liquid chromatography and positive ion electrospray mass spectrometry
      are applied to the determination of 16 carbamate, urea, and thiourea pesticides
      and herbicides in water. The electrospray mass spectra of the analytes were
      measured and are discussed and mobile-phase matrix effects were evaluated.
      Analyte positive ion abundances are generally inversely related to the
      concentration of acetic acid in the acetonitrile-water mobile phase in the range
      of 0.001-0.1% (v/v) acetic acid. Using an internal standard for quantitative
      analyses and no acid in the mobile phase, retention time precision, peak width
      precision, concentration measurement precision, mean recoveries, and instrument
      detection limits were determined in reagent water. The 16 analytes were also
      measured in fortified environmental water samples from a recreational lake, a
      groundwater well, a cistern, a farm pond, and drinking water. These measurements
      were at 5 ng/mL of each analyte, which is within the range expected for
      environmental pesticide and herbicide contaminants. The analytes were separated
      from the environmental water matrixes with an on-line extraction and
      concentration to provide rapid sample analyses without a slow off-line liquid
      liquid or liquid-solid-liquid extraction and extract concentration. Recoveries of
      12 of the analytes from 4 environmental water samples were in the range of 75
      124% with relative standard deviations in the range of 11-16%.

PMID- 11289448
TI  - Environmental policy implementation in rural China: a case study of Yuhang,
      Zhejiang.
AB  - The rapid growth of rural enterprises has transformed the Chinese countryside.
      Although rural industrialisation has resulted in increased financial well-being,
      it has also contributed to decreased environmental quality. While China has
      strong environmental protection laws, this paper will demonstrate that they are
      not being effectively implemented in a rural region in Zhejiang Province. This is
      due to a number of social, political, and economic barriers that prevent agencies
      from effectively enforcing environmental policies and regulatory mechanisms. This
      paper investigates the implementation of China's environmental policies through a
      case study in Yuhang County, Zhejiang Province. It demonstrates that the
      implementation of environmental impact assessment, discharge fees, and limited
      time treatment is limited by inadequate technology, low finances, limited human
      resources, poor public environmental awareness, faulty data, inferior agency
      reports, organizational conflict, relations based on guanxi, and low discharge
      fee prices.

PMID- 11289449
TI  - The interior-to-edge breakpoint distance as a guideline for nature conservation
      policy.
AB  - A method is proposed to quantify disturbance impact on isolated habitats. For
      every landscape patch, the breakpoint distance, defined as the penetration
      distance for which equality of interior and edge habitat is observed, can be
      calculated. Disturbance with equal impact at all patch sides is assumed. Effects
      of patch compactness, size, convolution, and perforation are discussed. The
      potential use of the measure for nature reserve design is discussed. The
      breakpoint distance follows the reserve design guidelines for individual patches,
      based on island biogeography and is consistent with the form and function
      principle. A large breakpoint distance is preferred for natural habitats. Small
      size, small compactness, intense convolution, and the occurrence of many gaps
      depress the breakpoint distance.

PMID- 11289450
TI  - Science, policy, stakeholders, and fish consumption advisories: developing a fish
      fact sheet for the Savannah River.
AB  - In recent years there has been a startling rise in the issuance of fish
      consumption advisories. Unfortunately, compliance by the public is often low. Low
      compliance can be due to a number of factors, including confusion over the
      meaning of advisories, conflicting advisories issued by different agencies,
      controversies involving health benefits versus the risks from consuming fish, and
      an unwillingness to act on the advisories because of personal beliefs. In some
      places, such as along the Savannah River, one state (South Carolina) had issued a
      consumption advisory while the other (Georgia) had not, although at present, both
      states now issue consumption advisories for the Savannah River. Herein we report
      on the development of a fish fact sheet to address the confusing and conflicting
      information available to the public about consuming fish from the Savannah River.
      The process involved interviewing fishers to ascertain fishing and consumption
      patterns, evaluating contaminant levels and exposure pathways, discussing common
      grounds for the provision of information, and consensus-building among different
      regulatory agencies (US Environmental Protection Agency, South Carolina
      Department of Health and Environmental Control, Georgia Department of Natural
      Resources) and the Department of Energy. Consensus, a key ingredient in solving
      many different types of "commons" problems, was aided by an outside organization,
      the Consortium for Risk Evaluation with Stakeholder Participation (CRESP). The
      initial role for CRESP was to offer scientific data as a basis for groups with
      different assumptions about risks to reach agreement on a regulatory response
      action. The process was an example of how credible science can be used to
      implement management and policies and provide a basis for consensus-building on
      difficult risk communication issues. The paper provides several lessons for
      improving the risk process from stakeholder conflicts, through risk assessment,
      to risk management. It also suggests that consensus-building and risk
      communication are continuing processes that involve assimilation of new
      information on contaminants and food-chain processes, state and federal law,
      public policy, and public response.

PMID- 11289451
TI  - Environmental management of quarries as waste disposal facilities.
AB  - Problems associated with the disposal of municipal solid waste have become a
      source of public concern worldwide as awareness of potential adverse
      environmental impacts and health threats from solid waste has increased.
      Communities are concerned about the generation and management of solid waste to
      the extent of refusing to allow new disposal facilities near their homes, often
      after witnessing the legacy of existing facilities. Under these conditions, the
      development of national policies for the management of solid waste becomes highly
      political, all while requiring appropriate technical solutions that ensure
      environmental protection and proper management plans that support an acceptable
      solution for the disposal of municipal solid waste. In some locations, the
      conversion of old quarries into well-engineered and controlled landfills appears
      as a promising solution to a continuously increasing problem, at least for many
      decades to come. This paper describes the environmental impacts associated with
      solid waste disposal in a converted quarry site and the mitigation measures that
      can be adopted to alleviate potential adverse impacts. Environmental management
      and monitoring plans are also discussed in the context of ensuring adequate
      environmental protection during and after the conversion process.

PMID- 11289452
TI  - Integrating local and scientific knowledge: an example in fisheries science.
AB  - Attempting to predict the spatial dynamics fish stocks, as required for
      management, is an ominous task given our incomplete understanding of biological
      and ecological mechanisms underpinning behavioral responses of fish. Large gaps
      still exist in our basic scientific knowledge. Nonetheless, the knowledge of
      fishers and fishery managers is not incorporated into our scientific analyses,
      even though such information is rich in observation since knowledge of fish
      behavior and distribution is a prerequisite for their profession. Combining such
      observations with more conventional scientific studies and theoretical
      interpretations provides a means by which we may bridge some gaps in our
      knowledge. Presented here is an example of how both local and scientific
      knowledge can be integrated in a heuristic model. The model, CLUPEX, is developed
      in the framework of a fuzzy logic expert system and uses linguistic statements
      written in natural language to capture and combine knowledge sources in the form
      of IF... THEN rules. The rules are inferred from interviews with experts and
      fishery professionals including fishers, fishery managers, scientists, and First
      Nations people. The knowledge base, comprised of the set of rules, is flexible in
      the sense that it can easily be modified to add additional information or change
      current information. Using input pertaining to biotic and abiotic environmental
      conditions, CLUPEX uses the rules to provide quantitative and qualitative
      predictions on the structure, dynamics and mesoscale distribution of shoals of
      migratory adult herring during different life stages of their annual life cycle.

PMID- 11289453
TI  - Natural and anthropogenic methane emission from coastal wetlands of South India.
AB  - For the first time, the methane emissions from diverse coastal wetlands of South
      India have been measured. Annual emission rates varied widely, ranging from 3.10
      mg/m2/hr (Bay of Bengal) to 21.56 mg/m2/hr (Adyar River), based on nature of the
      perturbance to each of the ecosystems studied. Distinct seasonality in methane
      emission was noticed in an unpolluted ecosystem (mangrove: 7.38 mg/m2/hr) and
      over a twofold increase was evident in the ecosystem that was disturbed by human
      activities (21.56 mg/m2/hr). The wide ranges in estimate suggest that
      methanogenesis occurs by both natural and anthropogenic activities in these
      coastal wetlands. Several physical and chemical factors such as salinity,
      sulfate, oxygen, and organic matter content influenced methanogenesis to a large
      degree in each of these ecosystems in addition to individual responses to human
      induced stress. For example, there was a clear negative correlation between
      oxygen availability (0.99), sulfate (0.98), and salinity (0.98) with CH4 emission
      in the Adyar river ecosystem. Although similar results were obtained for the
      other wetland ecosystems, CH4 emission was largely influenced by tidal
      fluctuations, resulting in a concomitant increase in methanogenesis with high
      sulfate concentrations. This study demonstrates that coastal wetlands are
      potentially significant sources of atmospheric methane and could be a greater
      source if anthropogenic perturbations continue at the current rate.

PMID- 11289454
TI  - Early secondary succession in bottomland hardwood forests of southeastern
      Virginia.
AB  - Addressing the need for reference sites that permit wetland managers to evaluate
      the relative success of wetland restoration efforts, this project examines the
      early successional properties of a chronosequence of 17 forested wetlands that
      have been clear-cut and allowed to naturally revegetate. Ordinations performed on
      the data using CANOCO software indicated three general types of communities- one
      dominated by bald cypress (Taxodium distichum) and water tupelo (Nyssa aquatica),
      one dominated by black willow (Salix nigra), and one with a species composition
      similar to that of a mature stand of bottomland hardwoods. These divisions were
      correlated with the percentage of stems originating as coppice on stumps leftover
      from the clear-cut. In particular, the bottomland hardwood stands were
      regenerating predominantly as coppice, while the cypress/tupelo and black willow
      stands were regenerating primarily as seedlings. As indicated by the earlier
      development of overstory basal area, coppice sites were also regenerating much
      faster. The hydrology of a site also exhibited a strong impact on the rate of
      regeneration, with the semipermanently to permanently flooded portions of sites
      often exhibiting little or no regeneration. The results indicate that, because of
      the overwhelming reliance on coppice sprouts as the main source of stems and the
      concomitant enhanced rates of regeneration, certain vegetative parameters of
      clear-cut bottomiand hardwood stands would not be effective benchmarks by which
      to judge the relative success of creation and restoration efforts.

PMID- 11289455
TI  - Traditional land-use systems and patterns of forest fragmentation in the
      highlands of Chiapas, Mexico.
AB  - The influence of slash-and-burn agriculture and tree extraction on the spatial
      and temporal pattern of forest fragmentation in two municipalities in the
      highlands of Chiapas, Mexico was analyzed. The data series were derived from two
      subsets of satellite images taken in 1974 and 1996. The analysis was based on
      area, edge, shape, core area, and neighbor indices. During the 22 years, the
      dense forest decreased by 8.9%/yr in Huistan and by 8.6%/yr in Chanal, while
      open/disturbed forest, secondary vegetation, and developed area increased in both
      municipalities. The total number of fragments increased by 1.4%/yr and 2.3%/yr in
      Huistan and Chanal, respectively. Dense forest showed the highest increase in the
      number of fragments (6%/yr in Huistan and 12%/yr in Chanal), while edge length,
      core area, and number of dense forest core areas decreased. The larger fragments
      of dense forest present in 1974 were divided into smaller fragments in 1996; at
      the same time, they experienced a process of degradation toward open/disturbed
      forest and secondary vegetation. Two different fragmentation patterns could be
      distinguished based on agricultural or forestry activities. Forest fragmentation
      did not occur as a continuous process; the pattern and degree of fragmentation
      were functions of land tenure, environmental conditions, and productive
      activities. The prevalence of rather poor soil conditions, small-holdings,
      growing human population densities, increasing poverty, and the absence of
      alternative economic options will maintain a high rate of deforestation and
      forest fragmentation in the studied region.

PMID- 11289456
TI  - Making it work: keys to successful collaboration in natural resource management.
AB  - This paper explores the positive aspects of collaboration in natural resources.
      Its purpose was to investigate participants' overall attitudes about keys to
      successful collaboration. The sample for the study consisted of 671 participants
      involved in 30 collaborative initiatives (CI) with the Forest Service. Using a
      mailed questionnaire, this study profiled the collaborative initiatives
      investigating purpose, problems addressed, groups involved, and years in
      existence. Respondents were queried on their overall perspectives on keys to
      successful collaboration. A total of more than 300 comments was collected from
      respondents and six categories emerged: development, information exchange,
      organizational support, personal communication, relationships/team building, and
      accomplishments. Continued research will need to explore the short- and long-term
      impacts of collaboration in natural resources.

PMID- 11289457
TI  - Managing radioactively contaminated land: implications for habitat diversity.
AB  - Radioactive contamination of agricultural land may necessitate long-term changes
      in food production systems, through application of selected countermeasures, in
      order to reduce the accumulation of radionuclides in food. We quantified the
      impact of selected countermeasures on habitat diversity, using the hypothetical
      case of two agricultural areas in Finland. The management scenarios studied were
      conversions from grassland to cereal production and from grassland and crop
      production to afforestation. The two study sites differed with respect to present
      agricultural production: one being predominantly cereal production and
      seminatural grasslands, while the other was dominated by intensive grass and
      dairy production. Some of the management scenarios are expected to affect
      landscape structures and habitat diversity. These potential changes were assessed
      using a spatial pattern analysis program in connection with geographic
      information systems. The studied landscape changes resulted in a more monotonous
      landscape structure compared to the present management, by increasing the mean
      habitat patch size, reducing the total habitat edge length and reducing the
      overall habitat diversity calculated by the Shannon diversity index. The degree
      of change was dependent on the present agricultural management practice in the
      case study sites. Where dairy production was predominant, the landscape structure
      changes were mostly due to conversion of intensive pastures and grasslands to
      cereal production. In the area dominated by cereal production and seminatural
      grasslands, the greatest predicted impacts resulted from afforestation of meadows
      and pastures. The studied management changes are predicted to reduce biodiversity
      at the species level as well as diminishing species-rich habitats. This study has
      predicted prominent side effects in habitat diversity resulting from application
      of management scenarios. These potential long-term impacts should be considered
      by decision-makers when planning future strategies in the event of radionuclide
      deposition.

PMID- 11289458
TI  - Simulated limnological effects of the Shasta Lake temperature control device.
AB  - We estimated the effects of a temperature control device (TCD) on a suite of
      thermodynamic and limnological attributes for a large storage reservoir, Shasta
      Lake, in northern California. Shasta Dam was constructed in 1945 with a fixed
      elevation penstock. The TCD was installed in 1997 to improve downstream
      temperatures for endangered salmonids by releasing epilimnetic waters in the
      winter/spring and hypolimnetic waters in the summer/fall. We calibrated a two
      dimensional hydrodynamic reservoir water quality model, CE-QUAL-W2, and applied a
      structured design-of-experiment simulation procedure to predict the principal
      limnological effects of the TCD under a variety of environmental scenarios.
      Calibration goodness-of-fit ranged from good to poor depending on the constituent
      simulated, with an R2 of 0.9 for water temperature but 0.3 for phytoplankton.
      Although the chemical and thermal characteristics of the discharge changed
      markedly, the reservoir's characteristics remained relatively unchanged.
      Simulations showed the TCD causing an earlier onset and shorter duration of
      summer stratification, but no dramatic affect on Shasta's nutrient composition.
      Peak inreservoir phytoplankton production may begin earlier and be stronger in
      the fall with the TCD, while outfall phytoplankton concentrations may be much
      greater in the spring. Many model predictions differed from our a priori
      expectations that had been shaped by an intensive, but limited-duration, data
      collection effort. Hydrologic and meteorological variables, most notably
      reservoir carryover storage at the beginning of the calendar year, influenced
      model predictions much more strongly than the TCD. Model results indicate that
      greater control over reservoir limnology and release quality may be gained by
      carefully managing reservoir volume through the year than with the TCD alone.

PMID- 11289459
TI  - Development of macroinvertebrate-based index for bioassessment of Idaho rivers.
AB  - Theoretical constructs, such as the river continuum concept, predict that the
      composition of benthic fauna in rivers will be different from that of headwater
      streams. There exists a need to modify, for use on larger rivers, the
      bioassessment techniques commonly used on small streams. Using aquatic
      macroinvertebrates and the "reference condition" approach, we developed and
      tested a multimetric index for use on the rivers of Idaho. Reference sites were
      selected to represent the best current conditions (i.e., least impacted) among
      Idaho rivers. The index performed well in distinguishing reference sites from
      sites displaying some form of anthropogenic impairment. Individual metrics used
      in the index included: number of EPT taxa, total number of taxa, percent dominant
      taxon, percent Elmidae, and percent predators. The index we developed for Idaho
      rivers was essentially a modification of a framework designed for small streams,
      suggesting that techniques, including data analysis, currently used for streams
      can be adapted for use on larger rivers. Adapting these methods for use in rivers
      is primarily a matter of (1) selecting metrics relevant to the rivers of
      interest; (2) expanding the field sampling to encompass the greater habitat area
      and, potentially, heterogeneity of rivers; and (3) selecting an appropriate form
      of data analysis. The approach we describe here should be applicable to
      geographic regions other than Idaho.

PMID- 11289460
TI  - Screening for diabetic retinopathy.

PMID- 11289461
TI  - Diabetes education research.

PMID- 11289462
TI  - The relationship between physicians' self-reported target fasting blood glucose
      levels and metabolic control in type 2 diabetes. The QuED Study Group--quality of
      care and outcomes in type 2 diabetes.
AB  - OBJECTIVE: To investigate the relationship between beliefs of physicians relative
      to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in
      a sample of their patients. RESEARCH DESIGN AND METHODS: Physicians' beliefs were
      investigated through a questionnaire sent to a sample of self-selected clinicians
      participating in a nationwide initiative aimed at assessing the relationship
      between the quality of care delivered to patients with type 2 diabetes and their
      outcomes. At the same time, physicians were asked to collect clinical data on a
      random sample of their patients, stratified by age (<65 vs. > or = 65 years).
      Mean HbA1c levels in the study population were thus evaluated according to target
      fasting blood glucose (FBG) used by their physicians. RESULTS: Of 456 physicians,
      342 (75%) returned the questionnaire. Among the responders, 200 diabetologists
      and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were
      always followed by the same physician and 1,294 of whom were seen by different
      physicians in the same structure on different occasions. Only 14% of the
      respondents used target FBG levels < or = 6.1 mmol/l, whereas 38% pursued values
      >7.8 mmol/l, with no statistically significant difference between diabetologists
      and GPs. The analysis of the relationship between FBG targets and metabolic
      control, restricted to those patients always seen by the same physician, showed a
      strong linear association, with mean HbA1c values of 7.0 +/- 1.6 for patients in
      the charge of physicians pursuing FBG levels < or = 6.1 mmol/l and 7.8 +/- 1.8
      for those followed by physicians who used target values >7.8 mmol/l. After
      adjusting for patients' and physicians' characteristics, the risk of having HbA1c
      values > 7.0% was highly correlated with physicians' beliefs. Patients followed
      by different physicians in the same unit showed a risk of inadequate metabolic
      control similar to that of patients followed by physicians adopting a
      nonaggressive policy. CONCLUSIONS: Doctors adopt extremely heterogeneous target
      FBG levels in patients with type 2 diabetes, which in turn represent an important
      independent predictor of metabolic control. To improve patient outcomes,
      physicians-centered educational activities aimed at increasing the awareness of
      the potential benefits of a tight metabolic control in patients with type 2
      diabetes are urgently needed.

PMID- 11289463
TI  - The impact of the diabetes control and complications trial and humalog insulin on
      glycohemoglobin levels and severe hypoglycemia in type 1 diabetes.
AB  - OBJECTIVE: This study was performed to determine the effects of the Diabetes
      Control and Complications Trial (DCCT) report in 1993 and the introduction of
      Lispro (Humalog) insulin in 1996 on glycemic control and on the number of severe
      hypoglycemic episodes in type 1 diabetic patients of various ages. RESEARCH
      DESIGN AND METHODS: Diabetes care parameters and HbA1c data from 884 subjects
      with type 1 diabetes were entered into our database at the time of clinic visits
      from 1993 through 1998. In addition, a questionnaire was sent to all patients to
      validate the number of insulin injections per day, the incidence of severe
      hypoglycemic episodes (as defined by the DCCT), and the use of Humalog insulin.
      Data were divided into four age-groups: < 5, 5-12, 13-18, and > 18 years of age.
      RESULTS: Longitudinal HbA1c levels declined significantly after the DCCT report
      in 1993-1996 (P < 0.001), but the number of severe hypoglycemic events increased
      (P < 0.001). A second decline in HbA1c levels was observed after the introduction
      of Humalog insulin in 1996 (P < 0.001). However, severe hypoglycemic episodes did
      not change (P = 0.26). CONCLUSIONS: Administration of Humalog resulted in an
      additional reduction in HbA1c levels beyond the reduction in HbA1c values after
      the DCCT report. In contrast to the increase in severe hypoglycemic events after
      the DCCT results, the number of severe hypoglycemic episodes did not increase
      after the introduction of Humalog, despite a further decrease in HbA1c values.

PMID- 11289464
TI  - Hospitalization among diabetic children and adolescents and the general
      population in Germany. German Working Group for Pediatric Diabetology.
AB  - OBJECTIVE: To compare hospitalization in a multicenter-based cohort of diabetic
      children and adolescents (aged 1-19 years) in Germany with that of the general
      population. RESEARCH DESIGN AND METHODS: Based on standardized documentation,
      hospital stays after manifestation were ascertained in diabetic subjects 1-19
      years of age in 1997. Hospitalization data in the general German population were
      derived from official statistics. Incidence rates and numbers of hospital days
      were estimated. Ratios of hospitalization incidences and numbers of hospital days
      between the diabetic and the general population were calculated. Costs for
      hospital care in the German diabetic population in 1997 were determined. RESULTS:
      A total of 5,874 patients came from 61 pediatric centers (52% male, age [mean +/-
      SD] 12.2 +/- 4.3 years, diabetes duration 4.6 +/- 4.4 years). Hospitalization
      incidence rates and hospital days per person-year (95% CI) were 0.27 (0.25-0.29)
      and 1.80 (1.75-1.84) in the diabetic population and 0.0948 (0.0946-0.0949) and
      0.6416 (0.6412-0.6420) in the general population. The standardized ratio of
      hospital incidences was 3.1 (2.9-3.2), and the ratio of numbers of hospital days
      was 2.8 (2.7-2.9). Costs for hospital care after manifestation were estimated to
      be $506 (U.S. dollars) per person-year and $12.4 million in the whole German
      diabetic population aged 1-19 years in 1997; including hospital stays at diabetes
      onset, total annual costs were $24 million ($970 per person-year). CONCLUSIONS:
      Diabetic children and adolescents in Germany had an approximately three times
      higher hospitalization risk and three times more hospital days than the age
      matched general population. Including hospitalization at diabetes onset, the
      annual costs of hospital care for the German diabetic population aged 1-19 years
      amounted to approximately 1% of all costs for hospital care in this age-group.
      Thus, costs were largely overproportional (diabetes prevalence 0.1%).

PMID- 11289465
TI  - Behavior therapy for families of adolescents with diabetes: maintenance of
      treatment effects.
AB  - OBJECTIVE: This study reports 6- and 12-month follow-up for the families of
      adolescents with diabetes who participated in a trial of Behavioral-Family
      Systems Therapy (BFST). RESEARCH DESIGN AND METHODS: A total of 119 families of
      adolescents with type 1 diabetes were randomized to 3 months of treatment with
      either BFST, an education and support (ES) group, or current therapy (CT). Family
      relationships, adjustment to diabetes, treatment adherence, and diabetic control
      were assessed at baseline, after 3 months of treatment, and 6 and 12 months
      later. This report focuses on the latter two evaluations. RESULTS: Compared with
      CT and ES, BFST yielded lasting improvements in parent-adolescent relationships
      and diabetes-specific conflict. Delayed effects on treatment adherence emerged at
      6- and 12-month follow-ups. There were no immediate or delayed effects on
      adolescents' adjustment to diabetes or diabetic control. CONCLUSIONS: BFST
      yielded lasting improvement in parent-adolescent relationships and delayed
      improvement in treatment adherence, but it had no effect on adjustment to
      diabetes or diabetic control. A variety of adaptations to BFST could enhance its
      impact on diabetes outcomes.

PMID- 11289466
TI  - Subclinical states of glucose intolerance and risk of death in the U.S.
AB  - OBJECTIVE: Although clinically evident type 2 diabetes is a well-established
      cause of mortality, less is known about subclinical states of glucose
      intolerance. RESEARCH DESIGN AND METHODS: Data from the Second National Health
      and Nutrition Examination Survey Mortality Study, a prospective study of adults,
      were analyzed. This analysis focused on a nationally representative sample of
      3,174 adults aged 30-75 years who underwent an oral glucose tolerance test at
      baseline (1976-1980) and who were followed up for death through 1992. RESULTS:
      Using 1985 World Health Organization criteria, adults were classified as having
      previously diagnosed diabetes (n = 248), undiagnosed diabetes (n = 183), impaired
      glucose tolerance (IGT) (n = 480), or normal glucose tolerance (n = 2,263). For
      these groups, cumulative all-cause mortality through age 70 was 41, 34, 27, and
      20%, respectively (P < 0.001). Compared with those with normal glucose tolerance,
      the multivariate adjusted RR of all-cause mortality was greatest for adults with
      diagnosed diabetes (RR 2.11, 95% CI 1.56-2.84), followed by those with
      undiagnosed diabetes (1.77, 1.13-2.75) and those with IGT (1.42, 1.08-1.87; P <
      0.001). A similar pattern of risk was observed for cardiovascular disease
      mortality. CONCLUSIONS: In the U.S., there was a gradient of mortality associated
      with abnormal glucose tolerance ranging from a 40% greater risk in adults with
      IGT to a 110% greater risk in adults with clinically evident diabetes. These
      associations were independent of established cardiovascular disease risk factors.

PMID- 11289467
TI  - Racial and ethnic differences in health care access and health outcomes for
      adults with type 2 diabetes.
AB  - OBJECTIVE: To evaluate health care access and utilization and health status and
      outcomes for type 2 diabetic patients according to race and ethnicity and to
      determine whether health status is influenced by health care access and
      utilization. RESEARCH DESIGN AND METHODS: National samples of Caucasians, African
      Americans, and Mexican-Americans were studied in the third National Health and
      Nutrition Examination Survey. Information on medical history and treatment of
      diabetes, health care access and utilization, and health status and outcomes was
      obtained by structured questionnaires and by clinical and laboratory assessments.
      RESULTS: Almost all patients in each race and ethnic group had one primary source
      of ambulatory medical care (92-97%), saw one physician at this source (83-92%),
      and had at least semiannual physician visits (83-90%). Almost all patients > or =
      65 years of age had health insurance (99-100%), and for those patients < 65 years
      of age, Caucasians (91%) and African-Americans (89%) had higher rates of coverage
      than Mexican-Americans (66%). Rates of treatment with insulin or oral agents (71
      78%), eye examination in the previous year (61-70%), blood pressure check in the
      previous 6 months (83-89%), and the proportion of hypertension that was diagnosed
      (84-91%) were similar for each race and ethnic group. Lower proportions of
      African-Americans and Mexican-Americans self-monitored their blood glucose
      (insulin-treated, 27 vs. 44% of Caucasians), had their cholesterol checked (62-68
      vs. 81%), and had their dyslipidemia diagnosed (45 vs. 58%). African-American and
      Mexican-American patients had a somewhat higher proportion than Caucasian
      patients, with HbA1c > or = 7% (58-66 vs. 55%), blood pressure > or = 140/90 mmHg
      among those with diagnosed hypertension (60-65 vs. 55%), and clinical proteinuria
      (11-14 vs. 5%). In contrast, they had better levels of total cholesterol (> or =
      240 mg/dl) (28 -30 vs. 34%) and HDL cholesterol (> or = 45 mg/dl) (46 -59 vs.
      38%), and African-American and Mexican-American men were less overweight than
      Caucasian men (BMI > or = 30) (34-37 vs. 44%), although the opposite was true for
      women. LDL cholesterol levels and the proportion of patients who smoked
      cigarettes or were hospitalized in the past year were similar among all three
      groups. In logistic regression analysis, there was little evidence that levels of
      blood glucose, blood pressure, lipids, or albuminuria were associated with access
      to or utilization of health care or with socioeconomic status. CONCLUSIONS: There
      are some differences by race and ethnicity in health care access and utilization
      and in health status and outcomes for adults with type 2 diabetes. However, the
      magnitude of these differences pale in comparison with the suboptimal health
      status of all three race and ethnic groups relative to established treatment
      goals. Health status does not appear to be influenced by access to health care.

PMID- 11289468
TI  - Diagnosing insulin resistance in the general population.
AB  - OBJECTIVE: Difficulties in measuring insulin sensitivity prevent the
      identification of insulin-resistant individuals in the general population.
      Therefore, we compared fasting insulin, homeostasis model assessment (HOMA),
      insulin-to-glucose ratio, Bennett index, and a score based on weighted
      combinations of fasting insulin, BMI, and fasting triglycerides with the
      euglycemic insulin clamp to determine the most appropriate method for assessing
      insulin resistance in the general population. RESEARCH DESIGN AND METHODS: Family
      history of diabetes, BMI, blood pressure, waist and hip circumference, fasting
      lipids, glucose, insulin, liver enzymes, and insulin sensitivity index (ISI)
      using the euglycemic insulin clamp were obtained for 178 normoglycemic
      individuals aged 25-68 years. Product-moment correlations were used to examine
      the association between ISI and various surrogate measurements of insulin
      sensitivity. Regression models were used to devise weights for each variable and
      to identify cutoff points for individual components of the score. A bootstrap
      procedure was used to identify the most useful predictors of ISI. RESULTS:
      Correlation coefficients between ISI and fasting insulin, HOMA, insulin-to
      glucose ratio, and the Bennett index were similar in magnitude. The variables
      that best predicted insulin sensitivity were fasting insulin and fasting
      triglycerides. The use of a score based on Mffm/I = exp[2.63 - 0.28ln(insulin) -
      0.31ln(TAG)] rather than the use of fasting insulin alone resulted in a higher
      sensitivity and a maintained specificity when predicting insulin sensitivity.
      CONCLUSIONS: A weighted combination of two routine laboratory measurements, i.e.,
      fasting insulin and triglycerides, provides a simple means of screening for
      insulin resistance in the general population.

PMID- 11289469
TI  - HbA1c measurement improves the detection of type 2 diabetes in high-risk
      individuals with nondiagnostic levels of fasting plasma glucose: the Early
      Diabetes Intervention Program (EDIP).
AB  - OBJECTIVE: Whereas new diagnostic criteria based on a fasting plasma glucose
      (FPG) of > 126 mg/dl (7.8 mmol/l) have improved the detection of diabetes,
      multiple reports indicate that many people with diabetes diagnosed by 2-h oral
      glucose tolerance test (OGTT) glucose measurements > or = 11.1 mmol/l (200 mg/dl)
      would remain undiagnosed based on this FPG criteria. Thus, improved methods to
      detect diabetes are particularly needed for high-risk individuals. We evaluated
      whether the combination of FPG and HbA1c measurements enhanced detection of
      diabetes in those individuals at risk for diabetes with nondiagnostic or
      minimally elevated FPG. RESEARCH DESIGN AND METHODS: We analyzed FPG, OGTT, and
      HbA1c data from 244 subjects screened for participation in the Early Diabetes
      Intervention Program (EDIP). RESULTS: Of 244 high-risk subjects studied by FPG
      measurements and OGTT, 24% of the individuals with FPG levels of 5.5-6.0 mmol/l
      (100-109 mg/dl) had OGTT-diagnosed diabetes, and nearly 50% of the individuals
      with FPG levels of 6.1-6.9 mmol/l (110-125 mg/dl) had OGTT-diagnosed diabetes. In
      the subjects with OGTT-diagnosed diabetes and FPG levels between 5.5 and 8.0
      mmol/l, detection of an elevated HbA1c (>6.1% or mean + 2 SDs) led to a
      substantial improvement in diagnostic sensitivity over the FPG threshold of 7.0
      mmol/l (61 vs. 45%, respectively, P = 0.002). Concordant FPG levels > or = 7.0
      mmol/l (currently recommended for diagnosis) occurred in only 19% of our cohort
      with type 2 diabetes. CONCLUSIONS: Diagnostic criteria based on FPG criteria are
      relatively insensitive in the detection of early type 2 diabetes in at-risk
      subjects. HbA1c measurement improves the sensitivity of screening in high-risk
      individuals.

PMID- 11289470
TI  - Role of common sequence variants in insulin secretion in familial type 2 diabetic
      kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor
      1alpha genes.
AB  - OBJECTIVE: We have demonstrated high heritability of insulin secretion measured
      as acute insulin response to glucose times insulin sensitivity (disposition
      index). Furthermore, we showed that obese normoglycemic family members of a type
      2 diabetic proband failed to compensate for the insulin resistance of obesity by
      increasing insulin secretion. In this study, we tested the primary hypotheses
      that previously described variants in the pancreatic sulfonylurea receptor gene
      (SUR1 or ABCC8), glucokinase (GCK) gene, or hepatocyte nuclear factor 1alpha
      (TCF1 or HNF1alpha) gene contribute to the inherited deficiencies of insulin
      secretion and beta-cell compensation to insulin resistance, as well as the
      secondary hypotheses that these variants altered insulin sensitivity. RESEARCH
      DESIGN AND METHODS: We typed 124 nondiabetic members of 26 familial type 2
      diabetic kindreds who had undergone tolbutamide-modified intravenous glucose
      tolerance tests for two variants of the ABCC8 (sulfonylurea) gene, two variants
      of the GCK gene, and one common amino acid variant in the TCF1 (HNF1alpha) gene.
      All family members were classified as normal or having impaired glucose tolerance
      based on oral glucose tolerance testing. We used minimal model analysis to
      calculate the insulin sensitivity index (S1) and glucose effectiveness (SG), and
      acute insulin response to glucose was calculated as the mean insulin excursion
      above baseline during the first 10 min after the glucose bolus. Disposition index
      (DI), a measure of beta-cell compensation for insulin sensitivity, was calculated
      as insulin sensitivity times acute insulin response. Effects of polymorphisms
      were determined using mixed effects models that incorporated family membership
      and by a likelihood analysis that accounted for family structure through
      polygenic inheritance. RESULTS: An intronic variant of the ABCC8 gene just
      upstream of exon 16 was a significant determinant of both DI and an analogous
      index based on acute insulin response to tolbutamide. Surprisingly, heterozygous
      individuals showed the lowest indexes, whereas the DI in the two homozygous
      states did not differ significantly. Neither the exon 18 variant nor the variants
      in the GCK and TCF1 genes were significant in this model. However, combined
      genotypes of ABCC8 exon 16 and 18 variants again significantly predicted both
      indexes of glucose and tolbutamide-stimulated insulin secretion. Unexpectedly, a
      variant in the 3' untranslated region of the GCK gene interacted significantly
      with BMI to predict insulin sensitivity. CONCLUSIONS: The exon 16 variant of the
      ABCC8 gene reduced beta-cell compensation to the decreased insulin sensitivity in
      the heterozygous state. This may explain the observation from several groups of
      an association of the ABCC8 variants in diabetes and is consistent with other
      studies showing a role of ABCC8 variants in pancreatic beta-cell function.
      However, our study focused on individuals from relatively few families.
      Ascertainment bias, family structure, and other interacting genes might have
      influenced our unexpected result. Additional studies are needed to replicate our
      observed deficit in beta-cell compensation in individuals heterozygous for ABCC8
      variants. Likewise, the role of the GCK 3' variant in the reduced insulin
      sensitivity of obesity will require further study.

PMID- 11289471
TI  - Corneal advanced glycation end products increase in patients with proliferative
      diabetic retinopathy.
AB  - OBJECTIVE: To evaluate corneal advanced glycation end product (AGE) fluorescence
      in patients with diabetes and in healthy control subjects. RESEARCH DESIGN AND
      METHODS: Corneal autofluorescence was measured in 26 eyes of 26 patients with
      type 2 diabetes (mean age 57.0 years; mean disease duration 12.2 years; mean
      HbA1c 7.1%) and 13 eyes of 13 healthy age-matched control subjects (mean age 57.9
      years). The patients with type 2 diabetes were divided into the following groups:
      patients without diabetic retinopathy (DR), patients without proliferative
      diabetic retinopathy (PDR), and patients with PDR. Corneal autofluorescence was
      measured by fluorophotometry with the wavelength that is characteristic of AGE
      fluorescence (excitation and emission 360-370 nm and 430-450 nm, respectively).
      We defined peak corneal autofluorescence levels as corneal AGE fluorescence
      values. We compared the corneal AGE fluorescence values in the four groups.
      RESULTS: In the PDR group (11.9 +/- 3.9 arbitrary units [mean +/- SD]), the
      corneal AGE fluorescence values were significantly higher compared with the
      control subjects (6.9 +/- 1.3 arbitrary units), the patients without DR (7.4 +/-
      2.1 arbitrary units), and the patients without PDR (6.9 +/- 2.2 arbitrary units)
      (P < 0.05). CONCLUSIONS: We found that corneal AGEs may increase in patients with
      diabetes and PDR compared with control subjects, patients without DR, and
      patients without PDR. In the patients with PDR, increased corneal AGEs may play a
      role in diabetic keratopathy.

PMID- 11289472
TI  - Effectiveness of platelet releasate for the treatment of diabetic neuropathic
      foot ulcers.
AB  - OBJECTIVE: The goal of this study was to specifically estimate the effectiveness
      of platelet releasate, a widely available treatment administered by a proprietary
      group of wound care centers (WCCs) for the treatment of diabetic neuropathic foot
      ulceration. RESEARCH DESIGN AND METHODS: Treatment effectiveness was estimated in
      a retrospective cohort study controlling for treatment selection bias using
      logistic regression-derived propensity scores. RESULTS: Platelet releasate was
      more effective than standard care. The relative risk for a wound to heal after
      treatment with platelet releasate compared with standard care at a WCC varied
      from 1.14 (95% CI 1.03-1.27) to 1.59 (1.49-1.70). The effect was greatest in
      those with the most severe wounds, i.e., large wounds that affect deeper
      anatomical structures. CONCLUSIONS: Within the limitations of the ability of
      propensity score analysis to control for selection bias, platelet releasate is
      more effective than standard therapy. This effect is more pronounced in more
      severe wounds. Unfortunately, severe wounds have not been evaluated in randomized
      clinical trials of new interventions. We encourage the inclusion of these
      patients in future trials.

PMID- 11289473
TI  - Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese
      nondiabetic subjects.
AB  - OBJECTIVE: To evaluate the effects of metformin on glucagon-like peptide 1 (GLP
      1) and leptin levels. RESEARCH DESIGN AND METHODS: A total of 10 obese
      nondiabetic male patients were studied before and after a 14-day treatment with
      2,550 mg/day metformin and were compared with 10 untreated obese control
      subjects. On days 0 and 15, leptin and GLP-1(7-36)amide/(7-37) levels were
      assessed before and after an oral glucose load during a euglycemic
      hyperinsulinemic clamp to avoid the interference of variations of insulinemia and
      glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7
      36)amide degradation in human plasma and in a buffer solution containing
      dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS: Leptin levels were
      not affected by the oral glucose load, and they were not modified after metformin
      treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7
      36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs.
      50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively),
      without affecting baseline GLP-1 levels. No variations of GLP-1 levels were
      observed in the control group. In pooled human plasma, metformin (0.1-0.5
      microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min
      incubation at 37 degrees C; similar results were obtained in a buffer solution
      containing DPP-IV. CONCLUSIONS: Metformin significantly increases GLP-1 levels
      after an oral glucose load in obese nondiabetic subjects; this effect could be
      due to an inhibition of GLP-1 degradation.

PMID- 11289474
TI  - Anemia with  erythropoietin deficiency occurs early in diabetic nephropathy.
AB  - OBJECTIVE: The normochromic normocytic anemia of erythropoietin (EPO) deficiency
      is recognized in advanced renal failure but not in early renal disease. The aim
      of this study was to determine whether anemia with EPO deficiency is found in
      type 1 diabetic patients with diabetic nephropathy in the absence of advanced
      renal failure and to compare them with patients with nondiabetic renal disease of
      similar severity. RESEARCH DESIGN AND METHODS: A total of 27 type 1 diabetic
      patients with diabetic nephropathy (DN), defined as having persistent proteinuria
      (mean 1,086 mg/day [CI 120-5,1901), a serum creatinine < or = 180 micromol/l, and
      retinopathy, were compared with 26 nondiabetic patients with glomerulonephritis
      (GN) and persistent proteinuria (1,874 mg/day [349-5,005]). The Hb concentration,
      red cell indexes, and serum EPO levels were measured, and other causes for the
      anemia were excluded. The EPO values were compared with a normal reference range
      obtained from nondiabetic patients with a microcytic anemia. The DN patients were
      tested for signs of diabetic peripheral and autonomic neuropathy. RESULTS: We
      found that 13 of the 27 DN patients were anemic (Hb 10.6 +/- 0.9 g/dl) in marked
      contrast to none of the GN patients (Hb 13.7 +/- 1.4 g/dl, P < 0.005). In the DN
      group, serum EPO concentrations failed to increase in response to anemia compared
      with the response seen in patients with microcytic anemia. Thus, the anemia of
      the DN group was associated with EPO deficiency. The anemic DN patients showed
      evidence of more severe proteinuria and diabetic neuropathy than the nonanemic DN
      patients. CONCLUSIONS: Anemia associated with EPO deficiency can occur early in
      DN before the onset of advanced renal failure, but does not normally occur in
      nondiabetic renal disease of similar severity. The pathogenesis requires
      elucidation.

PMID- 11289475
TI  - Antiatherogenic mitochondrial genotype in patients with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the significance of a longevity-associated mitochondrial
      genotype (Mt5178A) derived from a C --> A transversion at nucleotide position
      5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH
      dehydrogenase subunit 2 gene, in type 2 diabetic subjects. RESEARCH DESIGN AND
      METHODS: Mt5178 typing was done by polymerase chain reaction-restriction fragment
      length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic
      Japanese subjects, and the results were compared with the clinical
      characteristics. Then, the association of Mt5178 type with early atherosclerotic
      changes of the bilateral carotid arteries on ultrasonography was assessed in 412
      diabetic subjects randomly selected from the original 1,148 type 2 diabetic
      subjects, while maintaining the same frequency of Mt5178A and Mt5178C. RESULTS:
      The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was
      not different from that previously found in healthy blood donors (114 of 252;
      45%). Clinical characteristics regarding diabetes were not significantly
      different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694).
      However, the mean intima-media thickness (IMT) at six sites in the bilateral
      carotid arteries was significantly smaller in the Mrt5178A group than in the
      Mt5178C group (0.906 +/- 0.018 vs. 0.995 +/- 0.021 mm, mean +/- SEM, P = 0.022),
      and the Mt5178 type was significantly correlated with both the mean IMT and the
      presence of plaque on multiple regression analysis and discriminant analysis.
      CONCLUSIONS: The Mt5178A genotype may be unrelated to the etiology of type 2
      diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in
      type 2 diabetic individuals.

PMID- 11289476
TI  - The high prevalence of autoantibodies to tissue transglutaminase in first-degree
      relatives of patients with type 1 diabetes is not associated with islet
      autoimmunity.
AB  - OBJECTIVE: To determine the extent of celiac autoimmunity in type 1 diabetic
      patients and the overlap between islet and celiac autoimmunity in their
      nondiabetic relatives. RESEARCH DESIGN AND METHODS: IgA antibodies to tissue
      transglutaminase were determined in serum taken from 433 type 1 diabetic patients
      and 1,442 nondiabetic first-degree relatives. Samples with transglutaminase
      antibodies above the 97.5th percentile of 347 schoolchildren were also assayed
      for IgA anti-endomysial antibodies (EMAs). Markers of islet autoimmunity (islet
      cell antibodies and autoantibodies to insulin, glutamate decarboxylase. and
      protein tyrosine phosphatase IA-2) had previously been measured in all relatives.
      RESULTS: In the absence of known celiac disease, the prevalence of
      transglutaminase antibody levels above the 97.5th percentile of the
      schoolchildren was 13.4% in diabetic patients and 7.0% in nondiabetic relatives.
      ENMAs were found in addition to transglutaminase antibodies in 2.6% of probands
      and in 1.9% of first-degree relatives, but none of the schoolchildren.
      Transglutaminase antibodies were found to persist in 10 of 30 patients and in 30
      of 59 relatives with follow-up samples taken at least 2 years after the initial
      sample. Of 186 nondiabetic relatives with islet autoantibodies, only 10 also had
      transglutaminase antibodies. CONCLUSIONS: We found a high prevalence of celiac
      autoimmunity in patients and first-degree relatives of children with type 1
      diabetes, but we found limited overlap between islet and celiac autoimmunity in
      nondiabetic relatives. The high prevalence of celiac autoimmunity may be
      explained by shared genetic susceptibility and identifies a population within
      which screening for the disease may be justified.

PMID- 11289477
TI  - Elevated serum IP-10 levels observed in type 1 diabetes.
AB  - OBJECTIVE: Although most patients with type 1 diabetes are considered to have T
      cell-mediated autoimmune disease, a method of measuring of pancreatic beta-cell
      specific T-cell function in cases of type 1 diabetes has yet to be established.
      Here, we focused on interferon-inducible protein-10 (IP-10), a chemokine that
      promotes the migration of activated T-helper 1 (Th1) cells and measured serum IP
      10 levels in patients with human type 1 diabetes, which is regarded as a Th1
      mediated disease. RESEARCH DESIGN AND METHODS: Serum samples were obtained from
      diabetic patients, and the levels of autoantibodies (GAD and insulinoma
      associated protein-2 [IA-2]) and IP-10 were measured. Diabetic patients positive
      for either or both of the autoantibodies were classified as Ab+ type 1, and those
      negative for both were classified as Ab type 1. To evaluate islet antigen
      specific responses, peripheral blood from patients stimulated with or without GAD
      was used, and intracellular cytokine staining for flowcytometry was performed.
      RESULTS: The Ab+ and Ab- type 1 groups both showed a significantly higher serum
      IP-10 level than the healthy subjects (P < 0.001 and P < 0.05, respectively), and
      the IP-10 level in the recent-onset Ab+ subgroup was significantly higher than
      that in the established (longstanding) Ab+ subgroup (P < 0.002). Furthermore,
      there was a significant positive correlation between the serum IP-10 level and
      the number of GAD-reactive gamma-interferon-producing CD4+ cells in the Ab+ type
      1 group (P < 0.007). CONCLUSIONS: Our findings demonstrate that measurement of
      serum IP-10 concentrations is useful in patients with type 1 diabetes.

PMID- 11289478
TI  - Vitreous levels of vascular cell adhesion molecule and vascular endothelial
      growth factor in patients with proliferative diabetic retinopathy: a case-control
      study.
AB  - OBJECTIVE: To evaluate the intravitreous concentration of vascular cell adhesion
      molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy
      (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor
      (VEGF). RESEARCH DESIGN AND METHODS: Serum and vitreous fluid samples were
      obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with
      PDR and 20 nondiabetic control subjects with nonproliferative ocular disease.
      Both groups were matched by serum levels of VCGM-1 and VEGF. VCAM-1 and VEGF were
      determined by enzyme-linked immunosorbent assay. Statistics were determined using
      the Mann-Whitney U test and Spearman's rank correlation test. RESULTS: The
      intravitreous concentration of VCAM-1 was signifcantly elevated in diabetic
      patients with PDR compared with control subjects (26 ng/ml [19-118] vs. 22 ng/ml
      [20-47], P < 0.05). A direct correlation between VCAM-1 and total vitreous
      proteins was detected in diabetic patients (r = 0.64, P = 0.003), but not in
      control subjects. After adjusting for total intravitreous proteins, VCAM-1 was
      significantly lower in diabetic patients with PDR than in control subjects (8.2
      ng/ml [4-31.4] vs. 43.1 ng/ml [9.7-100], P < 0.001). Intravitreous VEGF
      concentrations were higher in patients with PDR than in control subjects in
      absolute terms (1.34 ng/ml [0.16-6.22] vs. 0.009 ng/ml [0.009-0.044], P < 0.0001)
      and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013
      ng/ml [0.003-0.035], P = 0.0001). Finally, the vitreous ratio of VCAM-1 to
      proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic
      patients (r = 0.74, P = 0.001) and control subjects (r = 0.84, P = 0.005).
      CONCLUSIONS: The low proportion of VCAM-1 in relation to total vitreal proteins
      observed in diabetic patients with PDR suggests that VCAM-1 is quenched by
      diabetic retina. In addition, the direct correlation detected between VCAM-1 and
      VEGF suggests that cellular adhesion and neovascularization may be linked
      processes.

PMID- 11289479
TI  - Prevalence and significance of retinopathy in subjects with type 1 diabetes of
      less than 5 years' duration screened for the diabetes control and complications
      trial.
AB  - OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated the
      powerlul impact of glycemic control on the progression of diabetic retinopathy. A
      large number of individuals (2,771) underwent stereoscopic color photography and
      fluorescein angiography as part of screening for participation in the DCCT. A
      subgroup of those individuals screened participated in the DCCT and underwent
      evaluation of their retinal vasculature semiannually for 4-9 years. These data
      were evaluated to determine how the 2000 American Diabetes Association position
      statement would apply to the DCCT experience. Specifically, the position
      statement indicates that the first dilated eye examination should be performed
      after 3-5 years' duration of diabetes because vision-threatening retinopathy
      virtually never develops in patients with type 1 diabetes during that interval
      RESEARCH DESIGN AND METHODS: We examined the experience of the DCCT in evaluating
      retinal photographs in 1,613 patients with type 1 diabetes of <5 years' duration
      and follow-up photographs every 6 months for 4-9 years in 855 members of that
      group. RESULTS: Of 1,613 subjects with type 1 diabetes of <5 years' duration
      screened for the DCCT, 716 (44.4%) had stereo-color photographic evidence of
      diabetic retinopathy, and 6 had preproliferative or worse pathology. Fluorescein
      angiography revealed retinopathy in 158 of 713 subjects with no evidence of
      retinopathy on color photographs. Thus, 874 (54.2%) of the original 1,613
      subjects had retinopathy at baseline. DCCT follow-up identified 341 additional
      individuals in whom retinopathy was developing before 5 years; 1,083 of 1,613
      (67.1%) individuals screened for the DCCT had retinopathy before 5 years'
      duration of diabetes. Those with retinopathy before 5 years had more rapid three
      step progression of vascular pathology than those with no retinopathy.
      CONCLUSIONS: Dilated eye examinations and retinal photography should be included
      in the routine management of type 1 diabetes during the first 5 years to identify
      the individuals at greatest risk for vision-threatening problems.

PMID- 11289480
TI  - Na/Li countertransport abnormalities in type 1 diabetes with and without
      nephropathy are familial.
AB  - OBJECTIVE: To determine whether there is a familial abnormality in erythrocyte
      Na/Li countertransport (CT) kinetics in the approximate one-third of type 1
      diabetic patients that succumb to a familial predisposition to nephropathy.
      RESEARCH DESIGN AND METHODS: Erythrocyte Na/Li CT kinetics were measured in
      nondiabetic first-degree relatives of type 1 diabetic patients with nephropathy
      (DNrel) (n = 32) or without nephropathy (DCrel) (n = 22) and normal control
      subjects ( n = 25). RESULTS: Increases in outside-site Na ion association rate
      constant and turnover rate of Na/Li countertransport (CT) in DNrels caused
      increases in Vmax/Km and Vmax, respectively. Thiol alkylation with N
      ethy]maleimide (NEM) modifies these kinetic parameters abnormally in nephropathy.
      With Na ions at the outside site of the transporter, thiol alkylation causes a
      large decrease in Vmax; but in their absence, Vmax is decreased in normal control
      subjects, unchanged in DCrels, or increased in DNrels. The relationship between
      Vmax values after thiol alkylation with or without Na ions was different in
      DNrels (P < 0.001). Kinetic parameters with and without thiol alkylation
      identified 60% of DNrels and 20% of DCrels as abnormal. The single-flux rate
      assay of Na/Li CT did not give this discrimination, and its use may cause
      discrepancy between studies. CONCLUSIONS: Clinically normal untreated DNrels have
      the same abnormality in Na/Li CT as the affected patients. DNrels had a metabolic
      syndrome with increased BMI and plasma triglycerides, but no elevation in blood
      pressure. Na/Li CT can detect those type 1 diabetic patients at risk of
      nephropathy who have a familial abnormality in a membrane thiol protein.

PMID- 11289481
TI  - Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes.
AB  - OBJECTIVE: To assess the impacts of insulin resistance and renal function on
      plasma total homocysteine (tHcy) levels in patients with type 2 diabetes with a
      wide range of nephropathy. RESEARCH DESIGN AND METHODS: Plasma tHcy levels were
      measured using the enzyme immunoassay method in 75 patients with type 2 diabetes
      and compared with those in 54 healthy control subjects. Insulin sensitivity
      indexes were assessed in patients with type 2 diabetes by hyperinsulinemic
      euglycemic clamp using artificial pancreas. RESULTS: Plasma tHcy levels and their
      log-translormed values (log tHcy) were significantly higher in all patients with
      diabetes than in control subjects (tHcy, 12.0 +/- 0.7 [SE] vs. 8.7 +/- 0.3
      micromol/l, P < 0.0001; log tHcy, 1.040 +/- 0.021 vs. 0.920 +/- 0.016 micromol/l,
      P < 0.0001). Plasma tHcy levels in patients with diabetes were significantly
      increased according to degree of nephropathy (P < 0.0001). On simple regression
      analyses, log tHcy correlated with insulin sensitivity indexes (r = -0.319, P =
      0.005) as well as creatinine clearance (r = 0.634, P < 0.0001) in all patients
      with diabetes. Multiple regression analyses showed that insulin sensitivity
      indexes (beta = -0.245) as well as creatinine clearance were independent
      contributors to log tHcy in all patients with diabetes (R2 = 0.750, P < 0.0001).
      For the 59 patients with diabetes with creatinine clearance >60 ml/min, insulin
      sensitivity indexes were also shown to be a significant contributor to log tHcy
      (beta = -0.438, R2 = 0.561, P < 0.001). CONCLUSION: Insulin resistance and renal
      function are independent determinants of tHcy levels in patients with type 2
      diabetes.

PMID- 11289482
TI  - A model-based method for assessing insulin sensitivity from the oral glucose
      tolerance test.
AB  - OBJECTIVE: Available insulin sensitivity (IS) methods based on the oral glucose
      tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an
      OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts
      glucose clearance in a glucose clamp. We validated OGIS against clamp data.
      RESEARCH DESIGN AND METHODS: OGIS requires glucose and insulin concentrations
      from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT).
      The formula includes six constants optimized to match the clamp results. For this
      purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic
      subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly
      underwent an OGTT and a 120 mU x min(-1) x m(-2) insulin infusion euglycemic
      clamp. Glucose clearance (Cl CLAMP), calculated as the ratio of glucose infusion
      to concentration during the last hour of the clamp, was compared with OGIS. OGIS
      was also tested on an independent group of 13 subjects with impaired glucose
      tolerance (IGT). RESULTS: OGIS and Cl CLAMP were correlated in the whole group (R
      = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2
      diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P <
      0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of
      variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in
      discriminating between groups (for OGIS, lean vs. obese: 440 +/- 16 vs. 362 +/-
      11 ml x min(-1) x m(-2), p < 0.001; lean vs. type 2 diabetes: 440 +/- 16 vs. 239
      +/- 7, P < 0.0001; obese vs. type 2 diabetes: 362 +/- 11 vs. 239 +/- 7, P <
      0.0001; results were similar for Cl CLAMP). The relationships between IS and BMI,
      fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin
      concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully
      consistent with established physiological principles. The performance of the
      index for the 3-h and 2-h OGTT was similar. CONCLUSIONS: OGIS is an index of IS
      in good agreement with the clamp. Because of its simplicity (only three blood
      samples required), this method has potential use for clinical investigation
      including large-scale epidemiological studies.

PMID- 11289483
TI  - Improvement of glycemic control by 1 year of insulin therapy leads to a sustained
      decrease in sE-selectin concentrations in type 2 diabetes.
AB  - OBJECTIVE: To examine whether and how improvement of glycemic control by long
      term insulin therapy decreases endothelial activation as measured by serum levels
      of the soluble adhesion molecules sE-selectin and vascular cell adhesion molecule
      (VCAM-1) and whether the drug used to lower blood glucose in addition to insulin
      influences such a response. RESEARCH DESIGN AND METHODS: Circulating adhesion
      molecules were measured before and after 3 and 12 months of therapy in 81
      patients with type 2 diabetes and 41 subjects without diabetes. The patients were
      treated with bedtime administration of NPH insulin combined with either
      glibenclamide (n = 19), metformin (n = 17), glibenclamide and metformin (n = 17),
      or morning administration of NPH insulin (n = 23). RESULTS: Before insulin
      therapy, serum sE-selectin level was 71% higher in the patients with type 2
      diabetes (77 +/- 4 ng/ml) than in the normal subjects (45 +/- 3 ng/ml, P <
      0.001), whereas levels of sVCAM-1 were comparable (420 +/- 25 vs. 400 +/- 11
      ng/ml, respectively). Glycemic control in all patients improved as judged from a
      decrease in HbA1c from 9.7 +/- 0.2 to 7.6 +/- 0.1% (P < 0.001). sE-selectin
      decreased to 67 +/- 4 ng/ml by 3 months (P < 0.001 vs. 0 months) and then
      remained unchanged until 12 months (70 +/- 4 ng/ml P < 0.001 vs 0 months). sVCnM
      1 levels at 12 months was similar to those at 0 months (416 +/- 25 ng/ml). The
      change in glycemic control, measured by HbA1c, but not in other parameters, was
      correlated with the change of sE-selectin (r = 0.41, P < 0.001) within the
      patients with type 2 diabetes. The decreases in sE-selectin were not different
      between the various treatment groups. CONCLUSIONS: We conclude that improvement
      in glycemic control by administration of insulin alone or insulin combined with
      either glibenclamide, metformin, or both agents induces a sustained decrease in
      sE-selectin, the magnitude of which seems to be dependent on the degree of
      improvement in glycemia. These data suggest that sE-selectin might provide a
      marker of effects of treatment of chronic hyperglycemia on endothelial
      activation.

PMID- 11289484
TI  - Blood pressure does not rise before the onset of microalbuminuria in children
      followed from diagnosis of type 1 diabetes. Oxford Regional Prospective Study
      Group.
AB  - OBJECTIVE: To examine whether a rise in blood pressure could be detected before
      the onset of microalbuminuria (MA) in a cohort of children followed from
      diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: The Oxford Regional
      Prospective Study is an incident cohort study of children with type 1 diabetes
      aged (mean +/- SD) 9.8 +/- 3.7 years at diagnosis. Subjects were assessed
      annually from diagnosis, with measurement of HbA1c, arterial blood pressure
      (random zero), and three urine samples for estimation of the albumin/creatinine
      ratio. During follow-up, 63 of 494 children developed MA at one or more annual
      assessments and were designated as cases for a nested case-control study. Each
      case was matched for sex and age at diagnosis with two normoalbuminuric control
      subjects. Blood pressure (BP) data were compared at corresponding years of
      diabetes duration. RESULTS: Cases with MA were similar to normoalbuminuric
      control subjects with respect to age and BMI, but they had higher mean HbA1c
      levels (mean difference 1.1%, P < 0.001). In the years before the onset of MA,
      the diastolic BP standard deviation score (SDS) was significantly higher than
      zero in cases (mean 0.49, P < 0.001) and in control subjects (0.50, P < 0.001).
      No difference could be detected between cases and control subjects before the
      onset of MA in either systolic or diastolic BP (mean difference systolic -1.2
      mmHg [95% CI -4.7 to 2.7], mean difference diastolic 0.1 mmHg [-2.4 to 2.6]).
      However, within the cases, the onset of MA was associated with elevations in
      systolic and diastolic BP SDSs (F = 16.1, P < 0.001; and F = 18.0, P < 0.001).
      BMI, but not HbA1c, was associated with systolic and diastolic BP SDSs in the
      subjects with MA (F = 0.6, P = 0.4; and F = 12.3, P = 0.001). However, the
      association of BP with MA remained signifcant for systolic BP (P = 0.001) and for
      diastolic BP (P < 0.001) after adjusting for BMI. CONCLUSIONS: A rise in systemic
      BP cannot be detected before the first appearance of MA in children with type 1
      diabetes. BP rises concurrently with the onset of MA and is also closely related
      to BMI.

PMID- 11289485
TI  - Effectiveness of self-management training in type 2 diabetes: a systematic review
      of randomized controlled trials.
AB  - OBJECTIVE: To systematically review the effectiveness of self-management training
      in type 2 diabetes. RESEARCH DESIGN AND METHODS: MEDLINE, Educational Resources
      Information Center (ERIC), and Nursing and Allied Health databases were searched
      for English-language articles published between 1980 and 1999. Studies were
      original articles reporting the results of randomized controlled trials of the
      effectiveness of self-management training in people with type 2 diabetes.
      Relevant data on study design, population demographics, interventions, outcomes,
      methodological quality, and external validity were tabulated. Interventions were
      categorized based on educational focus (information, lifestyle behaviors,
      mechanical skills, and coping skills), and outcomes were classified as knowledge,
      attitudes, and self-care skills; lifestyle behaviors, psychological outcomes, and
      quality of life; glycemic control; cardiovascular disease risk factors; and
      economic measures and health service utilization. RESULTS: A total of 72 studies
      described in 84 articles were identified for this review. Positive effects of
      self-management training on knowledge, frequency and accuracy of self-monitoring
      of blood glucose, self-reported dietary habits, and glycemic control were
      demonstrated in studies with short follow-up (<6 months). Effects of
      interventions on lipids, physical activity, weight, and blood pressure were
      variable. With longer follow-up, interventions that used regular reinforcement
      throughout follow-up were sometimes effective in improving glycemic control.
      Educational interventions that involved patient collaboration may be more
      effective than didactic interventions in improving glycemic control, weight, and
      lipid profiles. No studies demonstrated the effectiveness of self-management
      training on cardiovascular disease-related events or mortality; no economic
      analyses included indirect costs; few studies examined health-care utilization.
      Performance, selection, attrition, and detection bias were common in studies
      reviewed, and external generalizability was often limited. CONCLUSIONS: Evidence
      supports the effectiveness of self-management training in type 2 diabetes,
      particularly in the short term. Further research is needed to assess the
      effectiveness of self-management interventions on sustained glycemic control,
      cardiovascular disease risk factors, and ultimately, microvascular and
      cardiovascular disease and quality of life.

PMID- 11289487
TI  - American Diabetes Association 60th Scientific Sessions, 2000. Nephropathy.

PMID- 11289486
TI  - Recent advances in our understanding of insulin action and insulin resistance.

PMID- 11289488
TI  - Diabetic ketoacidosis associated with orlistat treatment.

PMID- 11289489
TI  - Association among hyperinsulinemia, family history of diabetes, and diminutive
      stature in normoglycemic premenopausal women.

PMID- 11289490
TI  - Regurgitation of blood into insulin cartridges in the pen-like injectors.

PMID- 11289491
TI  - Left ventricular hypertrophy and diastolic dysfunction in mitochondrial diabetes.

PMID- 11289492
TI  - Alterations in insulin-like growth factor binding protein-1 and sex hormone
      binding globulin levels in type 1 diabetic adolescents with microalbuminuria.

PMID- 11289493
TI  - Ethics in diabetic clinical trials.

PMID- 11289494
TI  - Erythromycin administration before sleep is effective in decreasing fasting
      hyperglycemia in type 2 diabetic patients.

PMID- 11289495
TI  - Lifestyle, obesity, and insulin resistance.

PMID- 11289496
TI  - Use of antidiabetic plants in Morocco and Quebec.

PMID- 11289497
TI  - Role of circulating vascular endothelial growth factor and hepatocyte growth
      factor in patients with coronary artery disease.
AB  - Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are
      thought to stimulate endothelial cell proliferation and induce angiogenesis in
      vivo. However. the precise mechanism responsible for VEGF and HGF release in
      patients with coronary artery disease is still unknown. We studied serum
      concentrations of VEGF and HGF in 20 patients with acute myocardial infarction
      (AMI), 20 patients with stable angina pectoris (AP) who had reversible perfusion
      defects on stress myocardial scintigraphy, and 16 patients with old myocardial
      infarction (OMI) who had no reversible defects on stress myocardial scintigraphy.
      The control group consisted of 20 patients with atypical chest pain who had
      angiographically normal coronary arteries. Serum VEGF and HGF concentrations were
      measured by enzyme-linked immunosorbent assay. Both the serum VEGF and HGF
      concentrations in the early stage of myocardial infarction in the patients with
      AMI were higher than those in the patients with AP and with OMI, and control
      patients. The VEGF concentration in the patients with AP was higher than in the
      patients with OMI, whereas the HGF concentration did not differ in the patients
      with AP and OMI. The VEGF concentration in AMI patients who had had preinfarction
      angina on admission was higher than that of patients who had had no preinfarction
      angina, whereas the HGF concentration did not differ between the two groups of
      patients. These results suggest that the serum VEGF concentration may reflect
      myocardial ischemia to a greater degree than the serum HGF concentration.

PMID- 11289498
TI  - Myocardial ischemia enhances the expression of acidic fibroblast growth factor in
      human pericardial fluid.
AB  - Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce
      angiogenesis in vivo. We have recently reported a marked increase of basic FGF in
      the pericardial fluid of patients with severe coronary stenosis and an increase
      in vascular endothelial growth factor (VEGF) in the pericardial fluid of patients
      with severe myocardial ischemia. The purpose of this study was to evaluate
      whether acidic FGF levels in the pericardial fluid are associated with severe
      myocardial ischemia. Immediately after incision of the pericardium in 48 patients
      during open-heart surgery, 3-5ml of pericardial fluid was obtained.
      Concentrations of basic FGF and VEGF in the pericardial fluid were measured using
      an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic
      FGF was newly developed using a rabbit antibovine acidic FGF antibody. The
      patients were divided into three groups (group A: 13 patients undergoing
      emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17
      patients undergoing elective CABG for stable angina; group C: 18 patients
      undergoing nonischemic open-heart surgery). The VEGF level in the pericardial
      fluid in group A was 68 +/- 59pg/ml, which was significantly higher than 33 +/- 9
      pg/ml in group B and 31 +/- 20 pg/ml in group C (P < 0.05). The concentrations of
      basic FGF in the pericardial fluid in groups A and B were 722 +/- 601 and 773 +/-
      763pg/ml, respectively, significantly higher than 263 +/- 349pg/ml in group C.
      The pericardial acidic FGF level in group A was 4,291 +/- 2,336 pg/ml, which was
      also significantly higher than 2,386 +/- 1,048 pg/ml in group B and 2,589 +/- 990
      pg/ml in group C (P < 0.05). The acidic FGF level correlated well with the level
      of VEGF (r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in
      pericardial fluid is associated with severe myocardial ischemia. This result
      indicates that the release of acidic FGF from the myocardial tissue into
      pericardial fluid is closely related to severe myocardial ischemia.

PMID- 11289499
TI  - Does repeated balloon inflation during coronary angioplasty induce ischemic
      tolerance? Analysis based on regional work.
AB  - It has been reported that repeated brief balloon inflation during coronary
      angioplasty (PTCA) alleviates myocardial dysfunction. However, it has also been
      reported that PTCA does not induce ischemic tolerance. Six patients with stable
      angina pectoris were recruited for this study. They were scheduled for PTCA to a
      significant stenosis of the proximal left anterior descending artery (LAD). All
      patients had single-vessel coronary artery disease without angiographic evidence
      of collateral circulation and with normal wall motion. After the stenosis of LAD
      was dilated by a 30-s inflation, 60 s of balloon inflation was performed five
      times at 60-s intervals. Left ventricular regional work was determined in the
      first and fifth inflations, and the data were compared. Regional work of the
      interventricular septum decreased immediately after the balloon inflation (the
      first inflation: 5.3 +/- 1.0 --> 0.6 +/- 0.2 mJ/cm3; fifth inflation; 5.3 +/- 1.0
      --> 0.6 +/- 0.3 mJ/cm3) and no statistically significant differences were found
      between the first and fifth inflations. After balloon deflation, the time
      required for the recovery of regional work was 30s in the fifth inflation,
      compared with 40 s in the first inflation (at 30 s after deflation, first
      inflation: 3.6 +/- 1.3 mJ/cm3; fifth inflation: 5.2 +/- 1.2 mJ/cm3). Although
      repeated balloon inflation did not change the amount of reduction in regional
      work, it improved the postischemic recovery of regional work. These results
      suggest ischemic tolerance.

PMID- 11289500
TI  - Optimal therapeutic range for oral anticoagulants in Japanese patients with
      prosthetic heart valves: a preliminary report from a single institution using
      conversion from thrombotest to PT-INR.
AB  - The thrombotest (TT) technique has been widely used in Japan for monitoring oral
      anticoagulant therapy (OAT). The therapeutic range was originally recommended to
      be 10%-25%. However, the International Committee for Standardization in
      Hematology/International Committee on Thrombosis and Hemostasis (ICSH/ICTH)
      recommended using the international normalized ratio of prothrombin time (PT-INR)
      for monitoring OAT. It is necessarv to use a universal standard measure for
      monitoring OAT in accordance with the ICSH/ISTH recommendation. We simultaneously
      measured TT and PT in blood samples from 1,157 patients on long-term warfarin
      therapy, and studied the correlation between TT and PT-INR. An excellent linear
      correlation was obtained between TT-INR and PT-INR with the regression equation
      PT-INR = 1.0420 TT-INR - 0.0987 (r = 0.905, P < 0.001). We also examined the
      correlation between the incidence of thromboembolism in 170 patients receiving
      warfarin therapy after prosthetic valve replacement; 50.5% received concomitant
      antiplatelet therapy. Thromboembolism occurred in 9 of 170 patients during a mean
      follow-up period of 2.44 years. The average TT values in patients with and
      without thromboembolism were 26.4% (PT-INR: 1.53) and 21.1% (1.73), respectively
      (P < 0.01). The incidence of thromboembolism did not differ significantly between
      patients on warfarin alone (average TT: 22.2%) and those on warfarin and
      antiplatelet agent (average TT: 20.9%). Our results suggest that the incidence of
      thromboembolism is low in Japan despite a less intensive regimen having been
      adopted.

PMID- 11289501
TI  - Strategies for CABG patients with carotid artery disease and perioperative
      neurological complications.
AB  - Postoperative neurological complications not only increase morbidity and
      mortality, but also prolong hospital stay and elevate hospital costs. From 1995,
      carotid artery duplex scanning (CADS) has been performed in our hospital as
      screening for cerebrovascular disease in patients undergoing nonemergency
      coronary artery bypass grafting (CABG). This study was designed to evaluate the
      usefulness of our strategy for preventing stroke during CABG. Between 1995 and
      1997, 179 patients underwent isolated CABG. Of the nonemergency CABG patients,
      146 underwent preoperative CADS. Three patients underwent a combined carotid
      endoarterectomy (CEA)/CABG procedure. One hundred and thirteen patients were men
      (77.3%), and the median age was 64, with a range of 39-82 years. The mean graft
      number was 2.7 +/- 0.9. Previous neurological events had occurred in 12 patients.
      Forty-five patients (30.8%) had abnormal CADS findings. Two (1.4%) of these
      patients had carotid stenosis > or = 90% in area, and five had total occlusion of
      the carotid artery. When the risk factors were evaluated, age and previous
      cerebrovascular disease (CVD) were found to be significantly higher in the group
      with abnormal CADS findings (P = 0.0012 and P = 0.0312). On multivariate
      analysis, the predictor of abnormal CADS findings were age and previous CVD (P <
      0.01 and P < 0.05). Six patients (3.3%) developed postoperative stroke due to
      emboli (five cases) or perioperative hypoperfusion (one case). Three patients who
      underwent the combined CEA/CABG procedure did not suffer from any neurological
      complications. Preoperative screening by CADS is helpful for evaluating the
      presence of carotid artery disease in patients undergoing CABG. Further
      investigations to clarify the carotid hemodynamics are important, and synthetic
      assessment will be required to determine the most appropriate operative strategy.

PMID- 11289502
TI  - Hyperhomocyst(e)inemia induces multiorgan damage.
AB  - Hyperhomocyst(e)inemia has been associated with the development of hypertension,
      stroke, and cardiovascular, cerebral/neuronal, renal, and liver diseases. To test
      the hypothesis that homocyst(e)ine plays an integrated role in multiorgan injury
      in hypertension, we employed: (1) spontaneously hypertensive rats (SHR) in which
      endogenous homocyst(e)ine levels are moderately high (18.1 +/- ().5 microM); (2)
      control age- and sex-matched Wistar Kyoto (WKY) rats in which homocyst(e)ine
      levels are normal (3.7 +/- 0.3 microM). To create the pathophysiological
      condition of hyperhomocyst(e)inemia, 20 mg/day homocyst(e)ine was administered
      for 12 weeks in (3) SHR (SHR-H) and in (4) WKY (WKY-H) rats. (5) Endogenous
      homocyst(e)ine levels were reduced slightly but not significantly from 18.1 +/-
      0.5 microM to 12.5 +/- 0.7 microM in SHR by folic acid administration (SHR-F).
      Plasma and tissue levels of homocyst(e)ine were determined by HPLC and
      spectrophotometric methods. Plasma and sympathetic ganglion (neuronal) matrix
      metalloproteinase (MMP) activity was measured by zymography. Activity of neuronal
      MMP was increased in hyperhomocyst(e)inemic rats as compared with controls. Mean
      arterial pressure (mmHg) was 95 +/- 5, 126 +/- 8,157 +/- 10, 188 +/- 5, and 165
      +/- 12 in WKY, WKY-H, SHR, SHR-H, and SHR-F, respectively. Urinary protein
      (mg/day) was 0.11 +/- 0.03, 0.88 +/- 0.22, 0.47 +/- 0.10, 0.89 +/- 0.21, and 0.81
      +/- 0.21 in WKY, WKY-H. SHR, SHR-H, and SHR-F, respectively, as measured by the
      Bio-Rad dye binding assay. The relationships between increased arterial pressure,
      plasma homocyst(e)ine, and urinary protein were delineated. Plasma and neuronal
      creatinine phosphokinase (CK) isoenzymes were measured by agarose gel
      electrophoresis. All three CK isoenzymes, i.e., MM, MB, and BB, specific for
      skeletal, cardiac, and nerve tissue, respectively, were induced following 12
      weeks' hyperhomocyst(e)inemia, suggesting multiorgan injury by homocyst(e)ine.
      Homocyst(e)ine induces endocardial endothelial cell (capillary) apoptosis and may
      reduce capillary cell density. Structural damage to aorta, myocardium, kidney,
      and renalureter was analyzed by histology. Results suggested an integrated
      physiological role of homocyst(e)ine in injury to the endothelial/epithelial cell
      lining in the respective organs.

PMID- 11289503
TI  - Plasma brain natriuretic peptide as a parameter to assess efficacy of continuous
      intravenous infusion of prostacyclin (epoprostenol) to treat severe primary
      pulmonary hypertension: a case report.
AB  - Continuous intravenous infusion of prostacyclin (epoprostenol) as a treatment for
      primary pulmonary hypertension (PPH) definitely improves the patient's quality of
      life, but few accurate parameters have been found to evaluate the efficacy of the
      treatment. We observed a patient with severe PPH whose plasma brain natriuretic
      peptide (BNP) level changed significantly as her condition and symptoms changed.
      Plasma BNP may be considered as one of the parameters for assessing the efficacy
      of prostacyclin treatment.

PMID- 11289504
TI  - A novel transposon tagging element for obtaining gain-of-function mutants based
      on a self-stabilizing Ac derivative.
AB  - A novel tagging system AcREH, designed for obtaining gain-of-function mutations,
      was prepared on the basis of a self-stabilizing Ac transposon derivative. The
      transposable element, DsAT, was constructed in a way that it can activate
      transcription of neighboring genes by two 35S promoters and/or by four tandem
      repeats of the enhancer fragment of this promoter. DsAT revealed somatic excision
      in the first generation of the tobacco transformants. The element exhibited
      germinal excision to the next generation, as demonstrated by PCR and Southern
      hybridization analysis. In spite of the structure of the element, which may
      inhibit the expression of the transposase gene, the frequency of germinal
      excision was comparable to or higher than those so far reported, suggesting the
      applicability of the element for gene tagging.

PMID- 11289505
TI  - Characterization of a two-component signal transduction system involved in the
      induction of alkaline phosphatase under phosphate-limiting conditions in
      Synechocystis sp. PCC 6803.
AB  - The gene products of sll0337 and slr0081 in Synechocystis sp. PCC 6803 have been
      identified as the homologues of the Escherichia coli phosphate-sensing histidine
      kinase PhoR and response regulator PhoB, respectively. Interruption of sll0337,
      the gene encoding the histidine protein kinase, by a spectinomycin-resistance
      cassette blocked the induction of alkaline phosphatase activity under phosphate
      limiting conditions. A similar result was obtained when slr0081, the gene
      encoding the response regulator, was interrupted with a cassette conferring
      resistance to kanamycin. In addition, the phosphate-specific transport system was
      not up-regulated in our mutants when phosphate was limiting. Unlike other genes
      for bacterial phosphate-sensing two-component systems, sll0337 and slr0081 are
      not present in the same operon. Although there are three assignments for putative
      alkaline phosphatase genes in the Synechocystis sp. PCC 6803 genome, only sll0654
      expression was detected by northern analysis under phosphate limitation. This
      gene codes for a 149 kDa protein that is homologous to the cyanobacterial
      alkaline phosphatase reported in Synechococcus sp. PCC 7942 [Ray, J.M., Bhaya,
      D., Block, M.A. and Grossman, A.R. (1991) J. Bact. 173: 4297-4309]. An alignment
      identified a conserved 177 amino acid domain that was found at the N-terminus of
      the protein encoded by sll0654 but at the C-terminus of the protein in
      Synechococcus sp. PCC 7942.

PMID- 11289506
TI  - Transcriptional activation of a maize calcium-dependent protein kinase gene in
      response to fungal elicitors and infection.
AB  - Plants respond to pathogen infection with the activation of the expression of
      pathogenesis-related genes, a response that involves Ca2+-regulated protein
      phosphorylation processes. We report here the isolation of a full-length
      complementary DNA encoding a calcium-dependent protein kinase (CPK) gene from
      maize. CPK genes occur in maize as members of a multigene family, but only one
      specific CPK gene, the ZmCPK10 gene here described, is transcriptionally
      activated in response to both fungal infection and treatment with fungal
      elicitors. Activation of the ZmCPK10 gene is extremely rapid. ZmCPK10 transcripts
      could be detected 5 min after elicitation and reached maximum levels at 30 min
      after treatment. Afterwards, there was a decline in the level of ZmCPK10
      transcripts followed by a basal level of accumulation which is maintained over
      the time period of elicitor treatment. The activation of this kinase is
      accompanied by an increase in the level of PRms mRNA, the PRms being a
      pathogenesis-related protein from maize whose expression is induced in maize
      tissues in response to fungal infection and treatment with fungal elicitors. In
      situ mRNA hybridization analysis revealed a remarkable cell-type specific pattern
      of expression of ZmCPK10 during growth and development of the elicitor-treated or
      fungus-infected seedling. Moreover, the ZmCPK10 gene is expressed only in those
      specific cell types in which the PRms gene is also expressed. The involvement of
      ZmCPK10 in the elicitor-induced signal transduction pathway leading to the
      activation of PRms gene expression is discussed.

PMID- 11289507
TI  - Assembly and plasma membrane targeting of recombinant immunoglobulin chains in
      plants with a murine immunoglobulin transmembrane sequence.
AB  - The cDNA encoding a full-length murine immunoglobulin gamma 1 heavy chain with
      its native leader sequence, transmembrane and intracellular domains was
      introduced into transgenic plants. Transformed plants expressed the recombinant
      polypeptide, but, in contrast to plants expressing the heavy chain without
      transmembrane sequence, the protein appeared to be associated with a plant cell
      membrane. Extraction of the membrane-associated heavy chain required the presence
      of a non-ionic detergent, and immunofluorescence studies of protoplasts
      demonstrated surface expression of membrane Ig heavy chain on up to 40% of the
      cells from a transgenic leaf. In plants expressing both the membrane Ig heavy
      chain and its partner light chain, functional antibody was also localised to the
      plant cell membrane and retention of the heavy chain at this site appeared to
      have no effect on the efficiency of antibody assembly. This approach of
      localising and accumulating recombinant antibody in cell membranes may have a
      number of applications, including passive immunisation against plant pathogens.

PMID- 11289508
TI  - Functional characterisation of urease accessory protein G (ureG) from potato.
AB  - The activation of the nickel metalloenzyme urease is a complex process. In
      bacteria, several urease accessory proteins are essential for incorporation of
      nickel into the active centre of urease. Comparatively little is known about the
      activation process and the proteins involved in plants. We cloned five different
      cDNAs encoding isoforms of urease accessory protein G (ureG) in potato. The 5'
      coding region of these cDNAs is highly polymorphic within Solanum tuberosum ssp.
      tuberosum, containing mainly a simple sequence repeat encoding histidine and
      aspartate. Mapping on an ultrahigh-density map of the potato genome and Southern
      blot analysis showed that the isoforms arise from allelic differences of a single
      copy gene which was located on chromosome 2. Expression analysis at the mRNA and
      protein levels indicated the presence of ureG in almost all tissues examined,
      consistent with the ubiquitous expression of urease. An attempt to correlate
      urease activity with ureG expression levels in different tissues was made.
      Allelic copies of ureG were expressed in a tissue-specific manner. UreG from
      potato and the Klebsiella aerogenes urease operon defective in bacterial ureG
      were co-expressed in Escherichia coli. The plant gene complements the K.
      aerogenes ureG mutation, demonstrating that it encodes a urease accessory protein
      and indicating a structural conservation between the plant and the bacterial
      urease activation complexes.

PMID- 11289510
TI  - Molecular characterization and expression study of a histidine auxotrophic mutant
      (his1-) of Nicotiana plumbaginifolia.
AB  - The histidine auxotroph mutant his 1(-) isolated from Nicotiana plumbaginifolia
      haploid protoplasts was first characterized to be deficient for the enzyme
      histidinol phosphate aminotransferase that is responsible for one of the last
      steps of histidine biosynthesis. Expression of the mutated gene at the RNA level
      was assessed by northern analysis of various tissues. Transcriptional activity
      was unimpaired by the mutation and, in contrast, a higher level of expression was
      obtained when compared to the wild-type. The cDNA sequence encoding the mutated
      gene was isolated by RT-PCR and compared to the wild-type gene. A single point
      mutation corresponding to the substitution of a G nucleotide by A was identified
      at position 1212 starting from the translation site. The alignment of the deduced
      amino acid sequences from the mutated and wild-type gene showed that this
      mutation resulted in the substitution of an Arg by a His residue at position 381.
      This Arg residue is a conserved amino acid for histidinol phosphate
      aminotransferase of many species. These results indicate that the identified
      mutation results in an altered histidinol phosphate aminotransferase enzyme that
      is unable to convert the substrate imidazole acetol phosphate to histidinol
      phosphate and thereby leads to the blockage of histidine biosynthesis. Possible
      consequences of this blockage on the expression of other amino acid biosynthesis
      genes were evaluated by analysing the expression of the dhdps gene encoding
      dihydrodipicolinate synthase, the first key enzyme of the lysine pathway.

PMID- 11289509
TI  - Identification and expression analyses of two genes encoding putative low
      affinity nitrate transporters from Nicotiana plumbaginifolia.
AB  - Higher plants have both high- and low-affinity nitrate uptake systems (HATS and
      LATS respectively). Here we report the isolation and characterization of two
      genes, NpNRT1.1 and NpNRT1.2, from Nicotiana plumbaginifolia whose structural
      features suggest that they both belong to the NRT1 gene family, which is involved
      in the LATS. Amino acid sequence alignment showed that the N. plumbaginifolia
      proteins have greater similarity to their corresponding tomato homologues than to
      each other. Genomic Southern blot analysis indicates that there are probably more
      than two members of this family in N. plumbaginifolia. Northern blot analysis
      shows that NpNRT1.2 expression is restricted strictly to roots, whereas NpNRT1.1,
      in addition to roots, is expressed at a basal level in all other plant organs.
      Likewise, differential expression in response to external treatments with various
      N sources was observed for these two genes: NpNRT1.1 can be considered as a
      constitutively expressed gene whereas NpNRT1.2 expression is dependent strictly
      on high nitrate concentrations. Finally, over-expression of a gene involved in
      the HATS does not lead to any modification of LATS gene expression.

PMID- 11289511
TI  - Characterization of a novel class of plant homeodomain proteins that bind to the
      C4 phosphoenolpyruvate carboxylase gene of Flaveria trinervia.
AB  - We are interested in the regulatory mechanisms responsible for the mesophyll
      specific expression of C4 phosphoenolpyruvate carboxylase (PEPCase). A one-hybrid
      screen resulted in the cloning of four different members of a novel class of
      plant homeodomain proteins, which are most likely involved in the mesophyll
      specific expression of the C4 PEPCase gene in C4 species of the genus Flaveria.
      Inspection of the homeodomains of the four proteins reveals that they share many
      common features with homeodomains described so far, but there are also
      significant differences. Interestingly, this class of homeodomain proteins occurs
      also in Arabidopsis thaliana and other C3 plants. One-hybrid experiments as well
      as in vitro DNA binding studies confirmed that these novel homeodomain proteins
      specifically interact with the proximal region of the C4 PEPCase gene. The N
      terminal domains of the homeodomain proteins contain highly conserved sequence
      motifs. Two-hybrid experiments show that these motifs are sufficient to confer
      homo- or heterodimer formation between the proteins. Mutagenesis of conserved
      cysteine residues within the dimerization domain indicates that these residues
      are essential for dimer formation. Therefore, we designate this novel class of
      homeobox proteins ZF-HD, for zinc finger homeodomain protein. Our data suggest
      that the ZF-HD class of homeodomain proteins may be involved in the establishment
      of the characteristic expression pattern of the C4 PEPCase gene.

PMID- 11289512
TI  - Identification of short promoter regions involved in the transcriptional
      expression of the nitrate reductase gene in Chlamydomonas reinhardtii.
AB  - In Chlamydomonas reinhardtii, the expression of the Nia1 gene encoding NAD(P)H
      nitrate reductase is controlled at the transcriptional level, positively by light
      and negatively by ammonium. Previous work has shown that the region -279 to +269
      with respect to the start site of transcription was sufficient to confer
      regulated expression of a promoterless arylsulfatase (Ars) reporter gene. To
      understand the mechanisms underlying this regulation, the -279 to +2 sequence was
      analysed for the presence of ammonium-responsive elements using either pJD54
      (promoterless Ars gene) or pJD100 (minimal beta-tubulin promoter-driven Ars
      gene). The region lying between -195 and -120 was shown to be dispensable.
      Essential responsive elements were found in four distinct regions between -231
      and -219, -120 and -100, -76 and -65 and -33 and -8. Each of these sequences is
      required for maximal expression in the absence of ammonium and a conserved
      GGA/TAGGGT motif is present in two of these regions. Several deletions within the
      region -33 to -77 were shown to partially relieve the transformants from the
      negative effect of ammonium. These experiments demonstrate that Nia1 expression
      is promoted by at least four elements between -231 and -8 and suggest that part
      of the repression by ammonium takes place through a proximal element located in
      the -51 to -33 sequence.

PMID- 11289514
TI  - Anti-cariogenic properties of tea (Camellia sinensis).
AB  - Various components in green and black tea, the beverages made by infusing
      appropriately processed dried leaves of Camellia sinensis, notably simple
      catechins, have properties in vitro that suggest an anti-cariogenic activity.
      These include: a direct bactericidal effect against Streptococcus mutans and S.
      sobrinus; prevention of bacterial adherence to teeth; inhibition of glucosyl
      transferase, thus limiting the biosynthesis of sticky glucan; inhibition of human
      and bacterial amylases. Studies in animal models show that these in-vitro effects
      can translate into caries prevention. A limited number of clinical trials in man
      suggest that regular tea drinking may reduce the incidence and severity of
      caries. If substantiated, this could offer a very economical public health
      intervention.

PMID- 11289513
TI  - Microarray-based survey of repetitive genomic sequences in Vicia spp.
AB  - A modified DNA microarray-based technique was devised for preliminary screening
      of short fragment genomic DNA libraries from three Vicia species (V. melanops, V.
      narbonensis, and V. sativa) to isolate representative highly abundant DNA
      sequences that show different distribution patterns among related legume species.
      The microarrays were sequentially hybridized with labeled genomic DNAs of
      thirteen Vicia and seven other Fabaceae species and scored for hybridization
      signals of individual clones. The clones were then assigned to one of the
      following groups characterized by hybridization to: (1) all tested species, (2)
      most of the Vicia and Pisum species, (3) only a few Vicia species, and (4)
      preferentially a single Vicia species. Several clones from each group, 65 in
      total, were sequenced. All Group I clones were identified as rDNA genes or
      fragments of chloroplast genome, whereas the majority of Group II clones showed
      significant homologies to retroelement sequences. Clones in Groups III and IV
      contained novel dispersed repeats with copy numbers 10(2)-10(6)/1C and two genus
      specific tandem repeats. One of these belongs to the VicTR-B repeat family, and
      the other clone (S12) contains an amplified portion of the rDNA intergenic
      spacer. In situ hybridization using V. sativa metaphase chromosomes revealed the
      presence of the S12 sequences not only within rDNA genes, but also at several
      additional loci. The newly identified repeats, as well as the retroelement-like
      sequences, were characterized with respect to their abundance within individual
      genomes. Correlations between the repeat distributions and the current taxonomic
      classification of these species are discussed.

PMID- 11289515
TI  - Enhancement of the virulence of Aeromonas caviae diarrhoeal strains by serial
      passages in mice.
AB  - Thirteen clinical Aeromonas caviae isolates from the faeces of 13 children with
      mild to severe diarrhoea were tested for enhancement of mouse lethality, adhesion
      ability, siderophore and cholera toxin cross-reactive (CTC) factor production, by
      four consecutive passages through mice by intraperitoneal injection of A. caviae
      suspensions. The passaged A. caviae strains were re-isolated from monomicrobic
      cardiac blood samples and inocula were prepared for the next passage. All A.
      caviae isolates possessed the ability to adhere to the mucosal epithelial surface
      of the rabbit small intestine. Serial passage in mice showed that the virulence
      of some isolates for mice was increased in terms of percentage mortality and a
      lowering of the LD50. For some of the isolates, but not all, serial passage
      appeared to increase siderophore production and adhesion to rabbit small
      intestinal cells. For the A. caviae isolates tested, increased values of the CTC
      factor were observed after passage. A clear correlation was observed between the
      lowering of LD50 and the enhancement of CTC factor production after passage in
      mice. These results indicate that the A. caviae isolates possessed virulence
      factors.

PMID- 11289516
TI  - Identification of a 43-kDa outer-membrane protein as an adhesin in Aeromonas
      caviae.
AB  - Aeromonas spp. are associated with intestinal and extra-intestinal infections.
      However, the virulence factors of A. caviae remain, for the most part, poorly
      known. This study examined the interactions involved in the adherence of A.
      caviae isolates Ae56, Ae391 and Ae398 to HEp-2 cells. All strains expressed high
      levels of aggregative adherence. Maximum adhesion occurred with bacteria grown at
      22 degrees C, but transmission electron microscopy did not reveal the presence of
      fimbrial structures on the bacterial cell surface. Outer-membrane proteins (OMPs)
      extracted from isolate Ae398, grown at 22 degrees C and 37 degrees C, showed
      similar SDS-PAGE protein profiles. Most proteins were < 60 kDa. A major 43-kDa
      protein was seen only in the boiled OMP extract. The biotinylated 43-kDa protein
      bound specifically to HEp-2 cells. Microbeads coated with the 43-kDa protein were
      also adherent to HEp-2 cells, and anti-43-kDa protein antibody blocked adherence
      of 43-kDa protein-coated latex beads. These data suggest that the 43-kDa OMP
      functions as an adhesin in A. caviae.

PMID- 11289517
TI  - Involvement of the heparan sulphate-binding proteins of Helicobacter pylori in
      its adherence to HeLa S3 and Kato III cell lines.
AB  - To determine whether Helicobacter pylori heparan sulphate-binding proteins
      (HSBPs) are involved in the adherence of H. pylori to HeLa and Kato III cells,
      monolayers were pre-incubated with various preparations and concentrations of H.
      pylori HSBPs at 37 degrees C, washed and then challenged with bacteria. HSBPs did
      not prevent but enhanced H. pylori adherence. However, challenging cultured cells
      with H. pylori previously incubated with rabbit anti-HSBP IgG resulted in
      significant inhibition of bacterial adherence. These data demonstrate that the
      extracellular HSBP plays an important role in promoting H. pylori attachment to
      Kato III and HeLa S3 cells, that adhesion of H. pylori to Kato III and HeLa S3
      cells is promoted by the presence of the 71.5-kDa extracellular HSBP and that
      rabbit polyclonal antibodies against this HSBP can inhibit adhesion of H. pylori
      to the cultured cell lines and detach cell-bound H. pylori.

PMID- 11289518
TI  - Cloning and characterisation of malE in Burkholderia pseudomallei.
AB  - No recombinant protein is available for serodiagnosis or skin test in the
      diagnosis of melioidosis. This report describes the cloning of the malE gene,
      which encodes an immunogenic protein of Burkholderia pseudomallei. Bi-directional
      DNA sequencing of malE revealed that the gene contained a single open reading
      frame encoding 416 amino acid residues with a predicted molecular mass of 44.4
      kDa. BLAST analysis showed that the putative protein encoded by malE is
      homologous to the maltose-binding protein (MBP) of other bacteria. It has 48% and
      63% amino acid identity and similarity with the MBP of Brucella abortus, and malE
      complementation assay showed that it partially complemented the function of the
      MBP of Escherichia coli. Several highly conserved regions among the MBP of B.
      pseudomallei, Br. abortus, Salmonella enterica serotype Typhimurium, E. coli and
      Enterobacter aerogenes were observed. These regions represent signatures A, B, C,
      D and F identified in the MBP of E. coli. Further sequence analysis revealed that
      the first 24 amino acid residues of the MBP of B. pseudomallei probably represent
      the N-terminal signal peptide of the protein. Similar to the signal peptide of
      the MBP of E. coli, Ent. aerogenes and S. Typhimurium, the MBP of B. pseudomallei
      contains two basic residues in the first eight amino acids, followed by a
      hydrophobic core, with the last three amino acids in the signal peptide being Ala
      Gln-Ala, conforming to the consensus sequence Ala-X-Ala at positions -3 to -1
      relative to the site of proteolytic cleavage for recognition by signal peptidase
      I. Further studies on serodiagnosis of melioidosis with recombinant MBP should be
      performed.

PMID- 11289519
TI  - Demonstration of the Rb1 lipopolysaccharide core structure in Salmonella strains
      with the monoclonal antibody M105.
AB  - The lipopolysaccharide (LPS) from 42 strains representing 19 Salmonella
      serogroups was differentiated into characteristic ladder-like profiles by SDS
      PAGE analysis. The core-specific antibody M105 (Ra, Rb1 and Rb2) was used in an
      immunoblot assay of SDS-PAGE-separated LPS molecules. The M105 antibody bound to
      the R-type LPS of 18 of the 20 Salmonella strains tested. The results demonstrate
      that S. enterica serotype Godesberg, S. Adelaide (one of two strains), S.
      Milwaukee, S. Niarembe, S. Bere and S. Arizonae (serogroup 63) have an atypical
      LPS core structure which is Rb1 type.

PMID- 11289520
TI  - Mucosal and systemic antibody responses to the lipopolysaccharide of Escherichia
      coli O157 in health and disease.
AB  - Mucosal immunity in the gastrointestinal (GI) tract is a primary defence against
      GI pathogens. We hypothesise that a mucosal response to lipopolysaccharide (LPS),
      especially to the common (core) determinants of GI pathogenic Escherichia coli
      strains, is protective. The aims of this study were to investigate the
      specificities, levels and development of humoral responses in health and GI
      disease to the R3 LPS core and O-polysaccharide of E. coli O157. The purpose was
      to try to predict whether vaccination or passive immunisation might induce
      protection. Wherever possible, paired whole gut lavage fluid (WGLF) and serum
      samples were collected for comparison of the mucosal and systemic responses.
      Matched saliva samples were also collected from some study groups. The patient
      groups included those with acute E. coli O157 disease (serum only), patients
      convalescing after E. coli O157 infections, and patients undergoing routine
      investigation for GI conditions but subsequently shown to be immunologically
      normal. Some samples of WGLF from patients with Crohn's disease (CRO) and
      ulcerative colitis (UC) were included to allow comparisons with patients with
      inflammatory conditions known to alter antibody secretion in the GI tract. The
      healthy groups from whom serum and saliva only were taken included blood donors,
      healthy volunteers and a group of slaughterhouse workers. This latter group was
      likely to have been exposed regularly to faecal bacteria from animals and
      antibody specificities might have been expected to be different from other
      healthy individuals. Levels and classes of antibodies were determined by ELISA
      with microtitration plates coated with polymyxin complexes of whole LPS extracted
      from E. coli O157 and LPS from the E. coli R3 rough mutant. Antibodies of IgG and
      IgM classes were measured in serum and IgA was measured in WGLF and saliva. IgG
      antibodies to the O157 LPS and the R3 core oligosaccharide were detected in the
      serum of healthy blood donors. Patients with acute E. coli O157 disease showed
      elevated levels of serum IgM to O157 LPS and R3, with IgG levels raised only to
      R3. In serum from convalescent patients, IgG to O157 LPS was significantly above
      the control groups only in the period 6-16 weeks after infection. Total IgA
      levels were similar in WGLF specimens from all groups, except the patients with
      UC, whose levels were much higher. Specific IgA levels were higher in the E. coli
      O157 convalescent group, but there were no significant correlations overall. UC
      patients had significantly lower levels of IgA to O157 and CRO patients had
      higher O157 IgA levels than UC patients and healthy volunteers. In serum,
      inhibition of ELISA showed that the response to the O157 LPS was due in part to a
      response to the R3 oligosaccharide component. This response was much more
      pronounced in the healthy and non-O157 groups than in convalescent patients.
      There was no correlation between specific IgA antibody levels in saliva and
      matched specimens of WGLF, and levels in sequential saliva specimens fluctuated
      widely. The significant IgG and IgA responses to the R3 core suggest that there
      is immunological memory to this oligosaccharide LPS component which may have a
      role in protection against E. coli LPS both systemically and locally in the GI
      tract. Boosting of this mucosal response to the LPS core, either naturally
      through exposure or by active or passive immunisation, may confer protection.
      Finally, antibody responses to E. coli O157 must be interpreted with caution, as
      the response detected is a sum of responses to the O-specific polysaccharide and
      the R3 core.

PMID- 11289521
TI  - Molecular analysis of skeletal tuberculosis in an ancient Egyptian population.
AB  - A paleomicrobiological study was performed on 37 skeletal tissue specimens from
      cadavers in the necropolis of Thebes-West, Upper Egypt, (2120-500 BC) and four
      from the necropolis of Abydos (3000 BC). The subjects had typical
      macromorphological evidence of osseous tuberculosis (n = 3), morphological
      alterations that were not specific, but probably resulted from tuberculosis (n =
      17), or were without morphological osseous changes (n = 21). DNA was extracted
      from these bone samples and amplified by PCR with a primer pair that recognised
      the Mycobacterium tuberculosis complex insertion sequence IS6110. To confirm
      specificity of the analysis, the amplification products of several samples were
      subjected to restriction enzyme digestion, or direct sequencing, or both. In 30
      of the 41 cases analysed, ancient DNA was demonstrated by amplification by the
      presence of the human beta-actin or the amelogenin gene and nine of these cases
      were positive for M. tuberculosis DNA. The results were confirmed by restriction
      endonuclease digestion and sequencing. A positive result for M. tuberculosis DNA
      was seen in two of the three cases with typical morphological signs of
      tuberculosis and amplifiable DNA, in five of 13 non-specific, but probable cases
      (including two cases from c. 3000 BC), but also in two of 14 cases without
      pathological bone changes. These observations confirm that tuberculosis may be
      diagnosed unequivocally in skeletal material from ancient Egypt, even dating back
      to c. 3000 BC. As a positive molecular reaction was observed in most of the
      typical cases of skeletal tuberculosis, in about one-third of non-specific, but
      probable tuberculous osseous changes and, surprisingly, in about one-seventh of
      unremarkable samples, this suggests that infection with M. tuberculosis was
      relatively frequent in ancient Egypt.

PMID- 11289522
TI  - Molecular epidemiology of airway colonisation by Aspergillus fumigatus in cystic
      fibrosis patients.
AB  - A total of 109 sequential and multiple Aspergillus fumigatus isolates
      corresponding to 41 samples from seven cystic fibrosis (CF) patients was typed by
      random amplification of polymorphic DNA (RAPD) with the primer NS3 from the
      fungal ribosomal gene 18S subunit, and by sequence-specific DNA primer (SSDP)
      analysis. RAPD typing of the isolates revealed 10 different genotypes, whereas
      nine genotypes were identified by SSDP. Combination of the two typing methods
      permitted the differentiation of 25 overall genotypes. The colonisation typing
      patterns differed greatly between patients colonised for <1 year by A. fumigatus
      and long-term colonised patients. Two of three recently colonised patients
      presented a large number of types even in the same sample, unlike the chronically
      colonised patients, who harboured a limited number of genotypes. In the latter,
      the occurrence of a dominant genotype, usually the overall genotype 2, tended to
      reflect to the duration of colonisation. Moreover, anti-catalase antibodies to A.
      fumigatus appeared in most cases to be in response to genotype 2. These findings
      suggest that some strains of A. fumigatus may be selected during prolonged
      colonisation of the airways in CF patients.

PMID- 11289523
TI  - Susceptibility to fluconazole of Candida clinical isolates determined by FUN-1
      staining with flow cytometry and epifluorescence microscopy.
AB  - The susceptibility of clinical Candida isolates to fluconazole was assayed by
      flow cytometry (FCM) and epifluorescence microscopy (EFM), with FUN-1 staining.
      In all, 25 clinical isolates of Candida spp. (12 sensitive, 3 dose-dependently
      sensitive and 10 resistant to fluconazole according to the NCCLS M27-A protocol)
      were treated with increasing concentrations of fluconazole during 1 or 2 h
      staining with FUN-1 for 30 min and analysed, respectively, by FCM at 575 nm (FL2)
      and by EFM. Fluconazole-susceptible strains showed an increased accumulation of
      FUN-1 in comparison with controls as determined by FCM and a reduced metabolic
      processing of the probe, confirmed by EFM. Conversely, resistant strains showed
      decreased FUN-1 staining and were able to process the probe. The fluconazole
      minimal inhibitory concentrations (MICs) determined by FCM or EFM after FUN-1
      staining compared very well with the corresponding values determined by the M27-A
      protocol, indicating that FUN-1 staining can be used as an alternative to the
      conventional method. MIC values of resistant strains, with the exception of C.
      krusei, were lower when treatment with fluconazole followed pre-incubation with
      0.1 mM sodium azide, a concentration known to inhibit the activity of efflux
      pumps. These results show that FUN-1 staining can be used as an alternative and
      rapid method for the assessment of susceptibility of Candida clinical isolates to
      fluconazole. Furthermore, the results suggest that resistance of Candida cells to
      fluconazole, with the exception of C. krusei strains, is likely to be due to the
      activity of efflux pumps.

PMID- 11289524
TI  - Failure of Mycoplasma pneumoniae infection to confer protection against
      Mycoplasma genitalium: observations from a mouse model.
AB  - Mycoplasma pneumoniae and M. genitalium are genomically distinct but share
      antigens that induce some serological cross-reactivity. Therefore, the
      possibility that M. pneumoniae infection of the human respiratory tract might
      provide immunity to M. genitalium infection of the genital tract was considered.
      Because of the difficulty of assessing this proposition in man, it was evaluated
      experimentally in a mouse model. Female BALB/c mice were susceptible to infection
      of the vagina with M. pneumoniae, whereas those infected previously in the
      oropharynx with M. pneumoniae were completely immune to infection of the vagina
      with this mycoplasma. However, all mice with such a respiratory tract infection
      were susceptible to infection of the vagina with M. genitalium. The findings
      suggest that an M. pneumoniae infection of the human respiratory tract is
      unlikely to influence infection of the genital tract by M. genitalium.

PMID- 11289525
TI  - Influence of infection of cells with bacteria associated with reactive arthritis
      on the peptide repertoire presented by HLA-B27.
AB  - Reactive arthritis (ReA) after infections with various gram-negative bacteria is
      strongly associated with the MHC class I molecule HLA-B27. It is supposed that
      the B27 molecule itself plays a role in the pathogenesis of ReA by presenting
      antigenic peptides to cytotoxic T lymphocytes. The peptide repertoires presented
      by Salmonella-, Shigella- and non-infected cells were compared to identify such
      peptides. From the peptides isolated from the B27 molecules of these cells,
      profiles were generated by reversed-phase chromatography and peaks present in the
      profiles from infected cells but not in profiles from non-infected cells were
      studied for their peptide compositions. Some sequences with identity to those in
      human histone H3, human ribosomal protein S17 and the heavy chain of HLA-B27
      itself were detected only in profiles from infected cells. All peptides
      identified from infected cells contained the B*2705 peptide-binding motif. The
      data suggest that HLA-B27-positive cells infected with ReA-inducing bacteria show
      an increased presentation of certain self-peptides. There was no evidence for
      altered peptide-binding specificity of B27 after infection. However, the
      interpretations were hampered by the variation in peptide presentation between
      different experiments.

PMID- 11289526
TI  - Successes and failures in occupational injury prevention.

PMID- 11289527
TI  - An overview of the injury severity score and the new injury severity score.
AB  - OBJECTIVE: The research was undertaken to describe the injury severity score
      (ISS) and the new injury severity score (NISS) and to illustrate their
      statistical properties. DESIGN: Descriptive analysis and assessment of the
      distribution of these scales. METHODS: Three data sources--the National Pediatric
      Trauma Registry; the Massachusetts Uniform Hospital Discharge Data Set; and a
      trauma registry from an urban level I trauma center in Massachusetts--were used
      to describe the distribution of the ISS and NISS among injured patients. RESULTS:
      The ISS/NISS was found to have a positively skewed distribution and
      transformation did not improve their skewness. CONCLUSION: The findings suggest
      that for statistical or analytical purposes the ISS/ NISS should not be
      considered a continuous variable, particularly if ISS/NISS is treated as a
      continuous variable for correlation with an outcome measure.

PMID- 11289528
TI  - Do self reported safety behaviours predict childhood unintentional injuries?
AB  - OBJECTIVE: The aim of this study was to investigate the validity of self reported
      safety behaviours as a proxy for injuries in unintentional injuries research.
      SETTING: The study population comprised parents and guardians of children aged 3
      12 months in 18 general practices throughout Nottingham (n = 764) who responded
      to a questionnaire on safety practices. METHOD: Injury data were collected by
      searching the primary and secondary care records of each child in the study.
      Safety behaviour was measured by computing a safety practices score from self
      reported safety practices for each respondent to a postal baseline questionnaire
      survey of safety behaviours. The score was used to classify families into low,
      medium, and high risk of injury occurrence. Two further scores were calculated,
      firstly for those safety practices which required obtaining an item of safety
      equipment, and secondly those safety practices requiring behavioural change
      without cost implications. RESULTS: High risk families were no more likely than
      low risk families to sustain an injury (odds ratio (OR) 1.08; 95% confidence
      interval 0.65 to 1.79). Medium risk families were also no more likely than low
      risk families to have a medically attended injury (OR 1.09; 0.73 to 1.61)
      suggesting no association between safety score and future medically attended
      injury. Similarly, compared to low risk families, medium risk (OR 0.93; 0.33 to
      2.61) and high risk (OR 0.46; 0.08 to 2.43) families were no more likely to have
      a child admitted to hospital with an injury. There was no correlation between the
      total number of injuries sustained during the study period and the baseline
      safety practices score (Spearman's rho = 0.004; p = 0.917). Subgroup analyses for
      safety behaviours requiring passive and active safety measures did not reveal
      significant associations with injury outcomes. CONCLUSION: Self reported safety
      behaviours do not appear to be good predictors of childhood unintentional
      injuries. Further research is required to ascertain valid proxy outcome measures
      for injury research.

PMID- 11289529
TI  - Research priorities for injury prevention.

PMID- 11289530
TI  - Comparison of work related fatal injuries in the United States, Australia, and
      New Zealand: method and overall findings.
AB  - OBJECTIVES: To compare the extent, distribution, and nature of fatal occupational
      injury in New Zealand, Australia, and the United States. SETTING: Workplaces in
      New Zealand, Australia, and the United States. METHODS: Data collections based on
      vital records were used to compare overall rates and distribution of fatal
      injuries covering the period 1989-92 in Australia and the United States, and 1985
      94 in New Zealand. Household labour force data (Australia and the United States)
      and census data (New Zealand) provided denominator data for calculation of rates.
      Case definition, case inclusion criteria, and classification of occupation and
      industry were harmonised across the three datasets. RESULTS: New Zealand had the
      highest average annual rate (4.9/100,000), Australia an intermediate rate
      (3.8/100,000), and the United States the lowest rate (3.2/ 100,000) of fatal
      occupational injury. Much of the difference between countries was accounted for
      by differences in industry distribution. In each country, male workers, older
      workers, and those working in agriculture, forestry and fishing, in mining and in
      construction, were consistently at higher risk. Intentional fatal injury was more
      common in the United States, being rare in both Australia and New Zealand. This
      difference is likely to be reflected in the more common incidence of work related
      fatal injuries for sales workers in the United States compared with Australia and
      New Zealand. CONCLUSIONS: The present results contrasted with those obtained by a
      recent study that used published omnibus statistics, both in terms of absolute
      rates and relative ranking of the three countries. Such differences underscore
      the importance of using like datasets for international comparisons. The
      consistency of high risk areas across comparable data from comparable nations
      provides clear targets for further attention. At this stage, however, it is
      unclear whether the same specific occupations and/or hazards are contributing to
      the aggregated industry and occupation group rates reported here.

PMID- 11289531
TI  - Work related spinal cord injury, Australia 1986-97.
AB  - OBJECTIVES: Little has been published before on the epidemiology and prevention
      of work related spinal cord injury (SCI). This study is the first national
      population based epidemiological analysis of this type of injury. It presents
      that largest case series ever reported. SETTING: The study utilises information
      from the Australian Spinal Cord Injury Register, which has full coverage of the
      population. METHODS: All newly incident cases of SCI from 1986 to 1997 were
      considered. RESULTS: Work related SCI accounted for about 13% of all traumatic
      cases of SCI over the period 1986-97. The labour force based incidence rate in
      Australia averaged four cases per million of population per annum over the
      period. The rate was highest among those aged 25-34 years (4.9/million) and among
      farmers (17.0/ million). Nearly half of the cases studied received their injury
      due to a fall. Motor vehicle crashes were also common and vehicle rollover was
      the predominant crash type. A high proportion of cases did not receive any
      compensation for their SCI. CONCLUSIONS: Although rare, SCI is one of the most
      severe and debilitating injuries that can be suffered in the workplace. As there
      is no cure for SCI, and the level of impairment does not improve substantially
      for the vast majority of cases even after rehabilitation, it is arguable that
      primary prevention should receive substantially greater emphasis.

PMID- 11289532
TI  - Surface characteristics, equipment height, and the occurrence and severity of
      playground injuries.
AB  - OBJECTIVES: To evaluate whether surface characteristics (absorption level (g
      max), material) and the height of play equipment are related to the occurrence
      and severity of injuries from falls. SETTING AND METHODS: During the summers of
      1991 and 1995, conformity of play equipment to Canadian standards was assessed in
      a random sample (n = 102) of Montreal public playgrounds. Surface absorption (g
      max) was tested using a Max Hic instrument and the height of equipment was
      measured. Concurrently, all injuries presenting at the emergency department of
      Montreal's two children's hospitals were recorded and parents were interviewed.
      Inspected equipment was implicated in 185 injuries. The g-max measurements (1995
      only) were available for 110 of these playground accidents. RESULTS: One third of
      falls (35 %) occurred on a surface exceeding 200 g and the risk of injury was
      three times greater than for g level lower than 150 (95% confidence interval (CI)
      1.45 to 6.35). On surfaces having absorption levels between 150 g and 200 g,
      injuries were 1.8 times more likely (95% CI 0.91 to 3.57). Injuries were 2.56
      times more likely to occur on equipment higher than 2 m compared with equipment
      lower than 1.5 m. Analysis of risk factors by severity of injury failed to show
      any positive relationships between the g-max or height and severity, whereas
      surface material was a good predictor of severity. CONCLUSIONS: This study
      confirms the relationships between risk of injury, surface resilience, and height
      of equipment, as well as between type of material and severity of injury. Our
      data suggest that acceptable limits for surface resilience be set at less than
      200 g, and perhaps even less than 150 g, and not exceed 2 m for equipment height.
      These findings reinforce the importance of installing recommended materials, such
      as sand, beneath play equipment.

PMID- 11289534
TI  - Sports activities related to injuries? A survey among 9-19 year olds in
      Switzerland.
AB  - BACKGROUND: Most data on sports injuries are gathered in clinical settings so
      that their epidemiology in the general population is not well known. OBJECTIVE:
      To explore the link between sports injuries with the type and the amount of
      sports activity and biological factors. METHODS: In 1996, 3,609 in-school
      adolescents 10-19 years (1,847 girls and 1,762 boys) participated in a regional
      survey. This included anthropometric measurements and a self administered
      questionnaire. RESULTS: Altogether 28.2% of girls and 35.9% of boys reported one
      or more sports injuries during the previous year and 2.1% of girls and 6.5% of
      boys reported at least one hospitalization due to a sports injury. Using the mean
      rate of injuries as reference level, some sports are highly related to injury
      occurrence: body building (relative risk (RR) 1.7, 95% confidence interval (CI)
      1.5 to 1.9), skateboarding and rollerskating (RR 1.6, 1.4 to 1.8), athletics (RR
      1.5, 1.3 to 1.7), snowboarding (RR 1.5, 1.4 to 1.6), basketball (RR 1.3, 1.2 to
      1.4), soccer (RR 1.3, 1.2 to 1.4), and ice hockey (RR 1.2, 1.1 to 1.3). Using a
      logistic regression, several variables associated with a higher risk of injury
      were identified: the amount of physical activity, high risk sports, and Tanner
      pubertal stages. CONCLUSION: The risk of sports injury increases not so much with
      age but with exposure to specific sports and with pubertal development.

PMID- 11289535
TI  - Injury patterns in rural and urban Uganda.
AB  - OBJECTIVES: To describe and contrast injury patterns in rural and urban Uganda.
      SETTINGS: One rural and one urban community in Uganda. METHODS: Community health
      workers interviewed adult respondents in households selected by multistage
      sampling, using a standardized questionnaire. RESULTS: In the rural setting,
      1,673 households, with 7,427 persons, were surveyed. Injuries had an annual
      mortality rate of 92/100,000 persons, and disabilities a prevalence proportion of
      0.7%. In the urban setting 2,322 households, with 10,982 people, were surveyed.
      Injuries had an annual mortality rate of 217/100,000, and injury disabilities a
      prevalence proportion of 2.8%. The total incidence of fatal, disabling, and
      recovered injuries was 116/1,000/year. Leading causes of death were drowning in
      the rural setting, and road traffic in the city. CONCLUSION: Injuries are a
      substantial burden in Uganda, with much higher rates than those in most Western
      countries. The urban population is at a higher risk than the rural population,
      and the patterns of injury differ. Interventions to control injuries should be a
      priority in Uganda.

PMID- 11289533
TI  - Proposed explanations for excess injury among veterans of the Persian Gulf War
      and a call for greater attention from policymakers and researchers.
AB  - INTRODUCTION: Death rates among US veterans of the Persian Gulf War were lower
      than rates among non-deployed veterans and the US population at large, with the
      exception of injury deaths; returning veterans were at significantly greater risk
      of injury mortality. Similar patterns of excess injury mortality were documented
      among US and Australian veterans returning from Vietnam. In spite of these
      consistent findings little has been done to explain these associations and in
      particular to determine whether or not, and how, war related exposures influence
      injury risk among veterans returning home after deployments. HYPOTHESIZED
      PATHWAYS: Several potential pathways are proposed through which injury might be
      related to deployment. First, increases in injury mortality may be a consequence
      of depression, post-traumatic stress disorder, and symptoms of other psychiatric
      conditions developed after the war. Second, physical and psychological traumas
      experienced during the war may result in the postwar adoption of "coping"
      behaviors that also increase injury risk (for example, heavy drinking). Third,
      greater injury risk may be the indirect consequence of increased experiences of
      ill defined diseases and symptoms reported by many returning veterans. Fourth,
      veterans may experience poorer survivability for a given injury event resulting
      in greater mortality but not morbidity. Finally, the process that selects certain
      individuals for deployment may lead to a spurious association between deployment
      status and injury mortality by preferentially selecting individuals who are risk
      takers and/or exposed to greater hazards. CONCLUSIONS: More research and
      attention from policymakers is needed to clarify the link between deployment and
      postwar increased risk of injury.

PMID- 11289536
TI  - Use of protective equipment by in-line skaters: an observational study.
AB  - OBJECTIVE: To determine the extent of protective equipment use (that is, helmets,
      wrist guards, elbow pads, knee pads) in a representative sample of in-line
      skaters. SETTING: Fifteen municipalities throughout the province of British
      Columbia. METHOD: A province-wide observational survey was conducted in the
      summer of 1999. Skaters were observed at four types of sites (commuter,
      recreational, neighbourhood, general community) in 15 municipalities to provide a
      representative sample of in-line skaters. RESULTS: The observed use of protective
      equipment by the 877 in-line skaters was relatively low: wrist guards 25%,
      helmets 13%, elbow pads 14%, and knee pads 10%. CONCLUSION: Despite the
      availability of relatively inexpensive protective equipment, few in-line skaters
      take advantage of the opportunity to protect themselves from injury. Policies and
      programs that serve to increase the use of protective equipment by in-line
      skaters are needed to help reduce the frequency of skating related injuries.

PMID- 11289537
TI  - Injury in young people with intellectual disability: descriptive epidemiology.
AB  - OBJECTIVES: To assess the public health importance of injury in a representative
      sample of young people with intellectual disability relative to the general
      population. SETTING: This study forms part of the Australian Child and Adolescent
      Development (ACAD) program examining emotional and behavioural problems in a
      cohort of young people with intellectual disability (IQ<70). The program has
      collected extensive biopsychosocial data from carers of subjects at two time
      intervals, 1990 (n = 579) and 1996 (n = 465). METHOD: Carer report of medically
      attended injury to subjects was collected for the first time during 1996 (age 5
      29 years) and supplemented with medical record injury data from hospitals and
      general practitioners for 147 of the ACAD sample and 110 supplementary subjects.
      These data were compared with general population injury data to assess relative
      epidemiological differences. RESULTS: Annual injury mortality and morbidity rates
      were 150/100,000 and 55.6/1000 persons, with age standardised mortality and
      morbidity ratios of 8 and 2 respectively. Males and females had similar injury
      rates. The rate for injury hospitalisations was twice that of the general
      population. Falls were more common and transport injury and intentional injury
      less common causes of injury morbidity compared with general population. The
      patterns of cause, circumstances, and severity of injury in young people with
      intellectual disability have more similarities with younger children than with
      their same age group in the general population. CONCLUSION: This study should
      alert clinicians and others to the increased risk for injury and possible further
      handicap in this population. It is essential that injury prevention programs be
      implemented and evaluated for their effectiveness in reducing the substantial
      additional burden of suffering, care and cost resulting from injury to young
      people with intellectual disability.

PMID- 11289538
TI  - A population based study of unintentional firearm fatalities.
AB  - OBJECTIVES: To describe the circumstances of fatal unintentional firearm injuries
      in a statewide population in a region of the United States with high firearm
      fatality rates and to compare to similar data from an earlier period in the same
      state. METHODS: Analyses of North Carolina medical examiner database (1985-94)
      and review of medical examiner case reports (1990-94) and comparison to similar
      data from 1979-82. RESULTS: A total of 390 unintentional shooting deaths occurred
      (0.59/100,000 population) between 1985-94 with the highest rate in the ages 15
      24. Between 1990-94, handguns were responsible for 59% of these deaths compared
      to 40% in the 1979-82 period. Younger victims were more likely to be shot by
      family or friends, though, 53% of all deaths were self inflicted. In 45 cases,
      the person firing the weapon was reported to believe that the gun was unloaded or
      had the safety device activated. CONCLUSIONS: This study demonstrates changes in
      patterns of unintentional firearm fatalities in North Carolina in two decades,
      particularly the increase in incidence of events involving handguns. The results
      highlight the need for additional attention to efforts governing access to
      firearms, particularly handguns; technological advances in designing safer guns,
      and additional emphasis on safe storage policies and practices.

PMID- 11289540
TI  - How much outpatient care is provided for injuries?
AB  - OBJECTIVE: To estimate the average number of outpatient visits, emergency
      department visits, and hospitalizations for injured patients. METHODS: The
      Medical Expenditure Panel Survey Household Component of 1996 is a weighted sample
      designed to represent the United States population. For each episode of injury
      the average number of office visits or outpatient contacts, emergency department
      visits, and hospitalizations were computed. Subsequently the ratio of outpatient
      to inpatient contacts for each type of injury was estimated. RESULTS: When asked
      to report on their medical problems for the previous six months, the majority of
      respondents who recalled injuries did not report contact with emergency
      departments or hospitalization. The average injury is associated with only 0.2 to
      0.3 emergency department visits. Sports related injuries were associated with
      0.03 hospitalizations. Gun related injuries were associated with 0.12
      hospitalizations. All types of injury were related with more than one episode of
      outpatient or office based care. The ratio of emergency department visits and
      outpatient visits to hospitalizations varies according to the nature of the
      injury. CONCLUSION: Policymakers interested in the cost of injury should account
      for the extensive outpatient utilization of injured patients.

PMID- 11289539
TI  - Evaluation of the Latrobe Valley Better Health Injury Prevention Program.
AB  - OBJECTIVE: To evaluate the Latrobe Valley Better Health Injury Prevention
      Program, a regional community based intervention in south east Victoria,
      Australia. METHOD: The evaluation design was quasiexperimental including pre
      intervention and post-intervention observations in a predominately town dwelling
      population of approximately 76,000. There was no comparison community. Process
      measures included key informant interviews. Impact evaluation utilised self
      reported changes in injury risk and protective factors, gathered by a random
      household telephone survey. Outcome evaluation was based on five years of
      emergency department injury surveillance data for the Latrobe Valley. RESULTS:
      The program built strategic partnerships, increasing the emphasis on local
      safety. Activities were implemented in the targeted areas of home, sport, and
      playground injuries. Some 47,000 educational contacts were made with the
      community and at least 6,000 resource items distributed. There were significant
      increases in home safety knowledge. Some changes in the areas of playground and
      sport safety were achieved after partnership development with relevant agencies.
      Poisson regression models showed significant decreases in the presentation rate
      for all home injury and for the more severe home injuries. CONCLUSION: This study
      clearly demonstrates the difficulty of conducting robust evaluation in the
      absence of readily available and reliable data and adequate budgets. The Latrobe
      Valley Better Health Program activities contributed to structural, environmental,
      and organisational changes that have the potential to reduce injury. The extent
      of this contribution beyond that made by the statewide injury prevention strategy
      is not able to be determined.

PMID- 11289541
TI  - Injury mortality among children and teenagers in Mexico, 1997.

PMID- 11289542
TI  - Hazards of unrestrained vehicle cargo.

PMID- 11289543
TI  - Cross country variation of fractures in the childhood population. Is the origin
      biological or "accidental"?

PMID- 11289544
TI  - Speed reductions, inequalities, and transport.

PMID- 11289545
TI  - Population preventable fraction of bicycle related head injuries.

PMID- 11289546
TI  - Foot-and-mouth disease confirmed in the UK.

PMID- 11289547
TI  - Decline in sales of antimicrobials used in food animals.

PMID- 11289548
TI  - Effects of vehicle movements during transport on the stress responses and meat
      quality of sheep.
AB  - Two groups of 26 lambs were transported for 15 hours either on smooth highways or
      on rougher secondary roads. Nine of the animals in each group were monitored for
      heart rate and the plasma levels of cortisol, creatine kinase and lactate
      dehydrogenase, before the journey began, after four, eight and 12 hours and at
      slaughter. The pH of the meat was measured 45 minutes and 24 hours postmortem and
      its colour was assessed 24 hours postmortem. The lambs transported on smooth
      roads had a lower heart rate and lower plasma cortisol concentrations after eight
      and 12 hours than the lambs transported on rougher roads. Twenty-four hours after
      slaughter the pH of the meat of the lambs transported on smooth roads was lower
      than that of the lambs transported on rougher roads.

PMID- 11289549
TI  - Magnetic resonance imaging of two normal equine brains and their associated
      structures.
AB  - Magnetic resonance images were obtained from two isolated horses' heads. Ten mm
      thick, T1-weighted images were taken with a 1.5 Tesla magnet and a body coil, and
      compared with the corresponding frozen cross-sections of the heads, relevant
      structures being identified and labelled at each level. The images should provide
      reference material for clinical magnetic imaging studies of horses' heads.

PMID- 11289550
TI  - Postmortem biochemical markers of experimentally induced hypomagnesaemic tetany
      in sheep.
AB  - Hypomagnesaemic tetany was induced in non-lactating and lactating ewes by feeding
      them semi-synthetic low magnesium diets containing additional potassium chloride
      and citric acid. Aqueous and vitreous humour were sampled from one eye at the
      time of death (fresh) and from the second eye after the head had been stored at
      ambient temperature for 24 hours (24-hour). There were significant relationships
      between the concentrations of magnesium in cerebrospinal fluid and plasma and its
      concentrations in fresh aqueous humour and fresh vitreous humour. Magnesium
      concentrations of < 0.33 mmol/litre in fresh aqueous humour and < 0.50 mmol/litre
      in 24-hour aqueous humour were associated with severe hypomagnesaemia and tetany.
      However, the concentration of magnesium in aqueous humour is relatively unstable
      and, unless the time of death was known accurately, its interpretation would be
      difficult. Magnesium concentrations of < 0.60 mmol/litre in fresh vitreous humour
      and < 0.65 mmol/litre in 24-hour vitreous humour were associated with severe
      hypomagnesaemia and tetany in adult sheep. The concentration of magnesium in
      vitreous humour was relatively stable for up to 48 hours postmortem.

PMID- 11289552
TI  - Molecular detection of Mycoplasma conjunctivae in English sheep affected by
      infectious keratoconjunctivitis.

PMID- 11289551
TI  - Evaluation of a commercially available enzyme-linked immunosorbent assay for the
      diagnosis of canine sarcoptic mange.
AB  - This study was designed to assess the accuracy of a commercial enzyme-linked
      immunosorbent assay for the diagnosis of canine scabies. Serum samples from 37
      dogs were examined blind; 12 had sarcoptic mange confirmed by the identification
      of mites in skin scrapings, 12 were atopic (with positive intradermal reactions
      to one or more aeroallergens, including Dermatophagoides farinae), and 13 were
      healthy dogs with no history of skin disease. Optical density values of more than
      0.16 were considered positive, 0.145 to 0.16 were considered questionable and
      less than 0.145 were considered negative. Ten of the 12 dogs with scabies were
      positive, all 12 atopic dogs were negative, and 11 of the 13 healthy dogs were
      negative and two were questionable.

PMID- 11289553
TI  - Identification of eae genes in Escherichia coli strains isolated from pigs with
      postweaning diarrhoea.

PMID- 11289554
TI  - Comparison of two treatments after retained fetal membranes on clinical signs in
      cattle.

PMID- 11289555
TI  - DNA polymorphism in Trypanosoma evansi isolates defined by randomly amplified
      polymorphic DNA-PCR.

PMID- 11289556
TI  - Foot-and-mouth disease outbreak.

PMID- 11289557
TI  - Providing prescriptions.

PMID- 11289558
TI  - Veterinary pharmacy.

PMID- 11289559
TI  - Fees and insurance.

PMID- 11289560
TI  - Fees and insurance.

PMID- 11289561
TI  - Angiostrongylus vasorum in dogs.

PMID- 11289562
TI  - Closure of the Thurso veterinary investigation centre.

PMID- 11289563
TI  - Intussusception at the ileocaecocolic junction in kittens.

PMID- 11289564
TI  - Brain control of penile erection.
AB  - The spinal cord contains a network that controls erection. This network can be
      activated by information from the periphery and by supraspinal nuclei. Besides
      anatomical studies that have detailed central pathways putatively involved in the
      central process of proerectile information, functional approaches have focused on
      pharmacological manipulations of specific systems, e.g. central dopaminergic
      pathways, leading to clinical perspectives in the treatment of erectile
      dysfunction. The present review focuses on some aspects of the recent research in
      the field.

PMID- 11289565
TI  - Phosphodiesterase isoenzymes as pharmacological targets in the treatment of male
      erectile dysfunction.
AB  - Based on the increasing knowledge of intracellular signal propagation in
      cavernous smooth muscle tone regulation, which is of major importance to the
      understanding of both the physiology of erection and the pathophysiology of
      erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have recently
      been introduced in the treatment of erectile dysfunction. The first promising
      clinical data on the use of the orally active PDE5 inhibitor Sildenafil in the
      treatment of erectile dysfunction were accompanied by boosting research
      activities on cavernous intracellular signal transduction and phosphodiesterase
      characterization with the aid of molecular biology and protein chemistry. The
      presence of mRNA transcripts specific for 14 different human phosphodiesterase
      isoenzymes and isoforms in human cavernous tissue was shown by RT-PCR: Three
      isogenes of PDEI, PDE2A and 10A, which hydrolyse cAMP as well as cGMP, the cAMP
      specific PDE3A, four isogenes of PDE4, PDE7A and PDE8A, as well as cGMP-specific
      PDEs PDE5A and PDE9A. Using anion exchange chromatography, the activities of PDE
      isoenzymes 2, 3, 4, and 5 were detected in cytosolic supernatants of human
      cavernous smooth muscle. To date, the efficacy and safety of several next
      generation PDE5 inhibitors for use in the treatment of male erectile dysfunction
      are under evaluation in vitro and in vivo. Further research will possibly allow
      identification of diagnostic tools for erectile dysfunction and of even more
      selective drugs in its therapy.

PMID- 11289566
TI  - Changes in ED therapy in the Viagra era.

PMID- 11289567
TI  - Key issues from the clinical trials of apomorphine SL.
AB  - The central nervous system has the capacity to enhance the activity of
      dysfunctional penile tissue in men with erectile dysfunction (ED). Phase III
      clinical trials have been conducted using Apomorphine SL (TAP Pharmaceuticals,
      Deerfield, IL) as a centrally acting treatment for ED. Apomorphine SL has been
      administered to over 3,000 men in over 75,000 doses. In three phase III crossover
      double blind studies 854 patients were given a total of 8,263 tablets of
      apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 years old
      and had multiple co-morbid conditions. Outcome measures included intercourse
      rates and erection rates on a per attempt basis as well as psychometric
      instruments and partner response evaluations. The results show that 74.1% of
      patients had moderate or severe grades of ED on inclusion into the studies, 31%
      had hypertension, 16% had documented coronary artery disease, 16% had
      dyslipidemia, and 16% had diabetes. Erections occurred rapidly (10-25 min). In
      54.4% of attempts at 4 mg (vs 33.8% placebo, P < 0.001) erections suitable for
      intercourse were documented. A majority of the attempts at intercourse (50.6%, P
      < 0.001) were successful at 4 mg a doubling of baseline rates. Mild nausea was
      the most common but infrequent side effect and the rare occurrence of syncope was
      the most significant. No cardiac deaths were attributed. It is concluded that the
      clinical trials of apomorphine SL demonstrate a safe and significant rate of
      restoration of erectile function by means of a central mode of action. Efficacy
      has been shown in men with cardiovascular disease and severe grades of ED.

PMID- 11289568
TI  - Vardenafil increases penile rigidity and tumescence in erectile dysfunction
      patients: a RigiScan and pharmacokinetic study.
AB  - The pharmacodynamic effect on penile rigidity and tumescence and the
      pharmacokinetic properties of single oral doses of 10 and 20 mg vardenafil, a new
      PDE5-inhibitor, were investigated in 21 erectile dysfunction patients. Patients
      were evaluated with RigiScan on three occasions in a randomized, placebo
      controlled, double-blind crossover fashion, while receiving visual sexual
      stimulation. Relative to placebo, a single dose of 10 mg vardenafil led to a mean
      increase in the duration of >60% penile rigidity of 24.4 min (95% CI: 7.4 to
      41.3) at the base and of 24.8 min (8.5 to 41.1) at the tip. For the 20-mg dose,
      the increase in duration of > 60% penile rigidity relative to placebo was 37.2
      min (20.2 to 54.1) at the base and 28.7 min (12.7 to 44.7) at the tip. Single
      doses of 10 and 20 mg vardenafil led to a rapid rise in the plasma concentrations
      of vardenafil, with a median tmax of 0.9 h and 0.7 h and a geometric mean Cmax of
      9.1 microg/l (geometric SD = 1.63) and 20.9 microg/l (geometric SD = 1.83),
      respectively. In the post-absorptive phase, the concentrations declined with an
      average terminal t 1/2 of 4.2 h (geometric SD = 1.27) and 3.9 h (geometric SD =
      1.31). The systemic exposure of vardenafil expressed as AUC normalized for dose
      and body weight was dose-proportional (associated 90% CI: -4 to 30%) as well as
      Cmax (associated 90% CI: -12 to 33%). The treatments were well tolerated. There
      was a small, clinically irrelevant reduction in blood pressure with a small
      compensatory rise in heart rate. There were no electrocardiographic effects or
      relevant changes of the safety laboratory screens. The observed pro-erectile
      properties, pharmacokinetic characteristics and safety profile make vardenafil a
      suitable candidate for further evaluation in the treatment of erectile
      dysfunction.

PMID- 11289569
TI  - Sildenafil citrate, a selective phosphodiesterase type 5 inhibitor: urologic and
      cardiovascular implications.
AB  - Erectile dysfunction (ED) occurs in varying degrees in an estimated 20 to 30
      million American men and is associated with adverse effects on quality of life;
      particularly personal well-being, family and social interrelationships. Research
      into ED has focused primarily on the physiologic mechanisms of corpus cavernosum
      smooth muscle relaxation, and penile erection as the end result of smooth muscle
      relaxation. These processes are mediated by cholinergic, nonadrenergic,
      noncholinergic (NANC, e.g., nitric oxide), vasoactive intestinal peptide (VIP),
      and potentially calcitonin gene-related peptide (CGRP) containing nerves. Release
      of nitric oxide following sexual stimulation from non-adrenergic, non cholinergic
      nerves and vascular endothelium activates guanylyl cyclase and induces
      intracellular cGMP synthesis. In turn, cGMP results in lowering intracellular
      concentrations, inhibits contractility of the penile smooth muscle, and induces
      an erectile response. Phosphodiesterase type 5 (PDE 5) is the predominant enzyme
      responsible for cGMP hydrolysis in trabecular smooth muscle. Activation of PDE 5
      terminates NO-induced, cGMP-mediated smooth muscle relaxation, and subsequent
      penile flaccidity. Sildenafil citrate is a potent PDE type 5 reversible and
      selective inhibitor which blocks cGMP hydrolysis effectively. FDA approval of
      sildenafil citrate as the first oral agent for ED in males has resulted in
      significant interest. We discuss the clinical and pharmacologic properties of
      sildenafil citrate as well as the urologic and cardiac implications.

PMID- 11289570
TI  - Central effects of sildenafil (Viagra) on auditory selective attention and verbal
      recognition memory in humans: a study with event-related brain potentials.
AB  - The purpose of this study was to assess possible central side-effects of
      sildenafil (Viagra) on attention and memory functions. Sildenafil and placebo
      were administered in young male subjects in a double-blind balanced cross-over
      design. Behavioral patterns and event-related brain potentials (ERP) were
      recorded in a spatial auditory attention and a visual word recognition task.
      While behavioral patterns did not reveal any overt effects of sildenafil,
      auditory ERPs were indicative of an enhanced ability to focus attention
      (amplitude enhancement of Nd-effect) and to select relevant target stimuli in the
      sildenafil condition (P3 component). In the memory task, CNS-effects of
      sildenafil were evident in a reduction of a negativity in the 150-250 ms range.
      No overt effects on behavior were observed. Nevertheless, the data reveal CNS
      effects of sildenafil necessitating further studies.

PMID- 11289571
TI  - Vasomax for the treatment of male erectile dysfunction.
AB  - This paper reviews laboratory and clinical data concerning oral phentolamine
      mesylate, Vasomax, an alpha-1, alpha-2 adrenergic receptor antagonist developed
      specifically for treatment of erectile dysfunction. A contemporary view of the
      neurovascular mechanisms in penile erection includes the effects of both smooth
      muscle relaxation and contraction. Contraction of the cavernosal arteries and
      trabecular smooth muscle appears to be predominantly under the control of alpha
      adrenergic innervation. Conversely, adrenergic blockade of alpha-1 and alpha-2
      receptors has been shown to facilitate penile erection in both animal and human
      models. The pharmacokinetic profile of Vasomax appears well suited for an oral
      erectogenic agent. Vasomax is rapidly absorbed and eliminated in normal males.
      Peak plasma concentrations are achieved in 30-60 min, and the half-life
      approximates 5-7 h. Food decreases the rate, but not the extent of
      bioavailability. Vasomax has low protein binding and is excreted primarily via
      urine and feces. There is a strong dose-response relationship in maximum plasma
      concentration (Cmax) and area under the curve (AUC), and there are no clear age
      related differences in absorption or elimination rates. Efficacy of Vasomax has
      been systematically evaluated in two (ZON300, ZON301) large-scale, placebo
      controlled trials, in addition to two long-term open-label studies. In both
      studies, Vasomax was associated with significant improvements in the erectile
      function domain scores of the International Index of Erectile Function (IIEF).
      Further improvements were noted as the duration of treatment and dose level were
      increased. The percentage of successful penetration attempts was also
      significantly improved with Vasomax compared to placebo. For patients who
      continued in open-label treatment with Vasomax, efficacy was generally well
      maintained. Vasomax was well tolerated by the majority of patients. The most
      common side effects observed were nasal congestion (10%), headache (3%),
      dizziness (3%), tachycardia (3%) and nausea (1%). Side effects were generally
      dose-related and in the mild-to-moderate range in all three studies. Furthermore,
      side effects seldom resulted in treatment discontinuation. Very few serious
      adverse events were observed in these trials. In summary, Vasomax appears to be
      effective in the treatment of male erectile dysfunction and well-tolerated by the
      majority of patients. The drug has a satisfactory side effect profile, without
      significant risk of cardiovascular effects. Results of clinical trials with
      Vasomax support the concept of adrenergic-blockade as a clinically relevant
      mechanism in the control of penile erection.

PMID- 11289572
TI  - Novel pharmacological approaches in the treatment of erectile dysfunction.
AB  - The pharmacological treatment of erectile dysfunction has taken central
      importance among therapeutic approaches for this increasingly recognized,
      widespread disorder. In the past decade and a half, the specialty of erectile
      dysfunction management has witnessed an enormous growth in basic scientific
      interest which has been translated impressively to the clinical arena.
      Discoveries of regulatory mechanisms involved in penile erection have been
      garnered both at peripheral neurologic and end organ levels and at central brain
      and spinal cord levels. These discoveries along with ongoing investigations in
      the field provide a firm foundation for implementing exciting and effective
      erectile dysfunction pharmacotherapies both now and in the future. The purpose of
      this report is to review the current trends and new directions in the
      pharmacotherapy of erectile dysfunction.

PMID- 11289573
TI  - Engineering of cells and tissues for treatment of erectile dysfunction.

PMID- 11289574
TI  - Oral alpha adrenoceptor blockade as a treatment of erectile dysfunction.
AB  - The sympathetic nervous system, via release of noradrenaline (NA) and stimulation
      of alpha adrenoceptors (ARs), is considered to be the prime determinant of
      cavernosal smooth muscle contraction and detumescence. A relative predominance of
      NA-induced contraction over nitric oxide-mediated relaxation may contribute to
      erectile dysfunction (ED). Therefore alpha AR antagonism seems an attractive way
      of treating ED, but so far the therapeutic success of oral treatment has been
      limited. Modest activity has been documented for the alpha2 AR antagonist,
      yohimbine, which is believed to act in the central nervous system. Phentolamine,
      mainly blocking alpha1 and alpha2 ARs peripherally, has been shown to have
      beneficial effects, but the efficacy compared to other alternatives, e.g.,
      sildenafil, has not been established. To improve oral treatment of ED with alpha
      AR antagonists, new drugs are required. However, little is known about central
      noradrenergic mechanisms involved in erection, or which alpha AR subtypes in the
      penile erectile tissues are the most important for mediation of contraction. It
      is still unclear what profile (alpha1 vs alpha2 ARs; selectivity for alpha1
      and/or alpha2 AR subtypes) is the most advantageous for an alpha AR antagonist in
      the treatment of ED.

PMID- 11289575
TI  - Cell-cell junctions in acantholytic diseases. Junction proteins in nonimmune and
      autoimmune acantholysis.

PMID- 11289576
TI  - Recombinant adeno-associated virus (rAAV) vector-mediated cotransduction of CD70
      and CD80 into human malignant melanoma cells results in an additive T-cell
      response.
AB  - Genetic modification of malignant melanoma cells by transduction of cDNA encoding
      costimulatory molecules, cytokines or tumor-associated antigens has been shown to
      induce antitumor immunity. An important step in this scenario is the activation
      of T cells. CD80 is a pivotal costimulatory molecule for T-cell activation.
      Another molecule with costimulatory activity is CD70. The purpose of this study
      was to evaluate the capacity of a combined expression of CD70 and CD80 on
      melanoma cells to amplify an antitumor response in vitro. Therefore, the CD70-
      and CD80-negative human malignant melanoma cell line Colo679 was transduced with
      adeno-associated virus vectors carrying either CD70 or CD80. The resulting cell
      strains Colo679-CD70, -CD80 and -CD70/CD80 showed strong expression of CD70, CD80
      or both, respectively. As expected, the T-cell response to CD70-positive
      malignant melanoma cells was substantially weaker than to the CD80-positive
      cells. However, the combined expression of CD70 and CD80 resulted in a T-cell
      response clearly superior to the single expression of CD80 or CD70 alone. These
      results provide evidence that CD70 plays an additional role in T-cell activation
      and should be considered as a molecule of interest in the design of immune gene
      therapy strategies for the treatment of malignant melanoma.

PMID- 11289577
TI  - Identification of leukemia inhibitory factor as a potent mast cell growth
      enhancing factor produced by mouse keratinocyte cell line, KCMH-1.
AB  - Inoculation of KCMH-1 cells, a keratinocyte-derived cell line established from a
      chemically induced skin tumor, into the skin of mice results in accumulation of
      mast cells around the resulting tumors. The conditioned medium of KCMH-1 cells
      enhances the growth of mast cells in vitro when they are cultured in the presence
      of NIH/3T3 fibroblasts, suggesting an important role for keratinocytes in mast
      cell hyperplasia in the skin. The aim of this study was to identify this mast
      cell growth-enhancing factor (MCGEF) by screening a KCMH-1 cDNA library. We first
      established a polyclonal antibody raised against the partially purified factor
      obtained from KCMH-1-conditioned medium which neutralized the MCGEF activity in
      KCMH-1-conditioned medium. Expression cloning of 1 x 10(6) cDNAs from the KCMH-1
      cDNA library led to 16 cDNAs. One of these cloned cDNAs was found to be leukemia
      inhibitory factor (LIF). Both LIF produced by COS cells and the recombinant
      protein obtained commercially showed MCGEF activity when added to mast
      cell/fibroblast cocultures. MCGEF activity in KCMH-1-conditioned medium was
      completely neutralized by an anti-LIF monoclonal antibody. These results suggest
      that MCGEF produced by KCMH-1 cells is identical to LIF.

PMID- 11289578
TI  - Vascular endothelial growth factor (VEGF) induces human Langerhans cell
      migration.

PMID- 11289579
TI  - Skeletal troponin-I release in orthopedic and soft tissue injuries.
AB  - The skeletal isoform of troponin-I (sTnI) is a myofibrillar protein highly
      specific for myoskeletal injury. We used an indirect immunoenzymometric assay
      method with high analytical sensitivity to measure sTnI in patients with soft
      tissue injury and in orthopedic patients. We assessed 20 soft-tissue injury
      patients and 16 orthopedic patients for sTnI, cardiac troponin-I (cTnI), creatine
      kinase (CK), myoglobin, and elastase within 24h of injury, in comparison with 17
      control subjects. The mean (SD) ng/ml value for sTnI was higher in orthopedic
      patients (15.25 +/- 2.4) and in soft-tissue injury patients (10.41 +/- 1.8) than
      that in controls (2.5 +/- 0.9) P < 0.001, P < 0.05 respectively. Cardiac TnI was
      not detectable in any subjects (below the assay detectable limit of 0.3ng/ml). CK
      was significantly higher in orthopedic patients than in controls (P < 0.005) and
      myoglobin and elastase were not significantly changed in patients samples. The
      assay appeared to be suitable as a supplementary tool of reliability and
      relevance, for the study, identification, and diagnosis of skeletal muscle
      specific injuries in humans.

PMID- 11289580
TI  - The original hole-in-one guide for atlantoaxial transarticular screw fixation.
AB  - Atlantoaxial fusion by transarticular screw fixation provides firm fixation, and
      good results have been reported. However, there are also problems, such as injury
      of the vertebral artery at the time of screw insertion. For accurate facet
      fusion, we developed a new hole-in-one guide for screw fixation and obtained good
      results with its use. In 60 adult subjects. we measured the antero-posterior and
      transverse axes and determined the center of the atlantoaxial surface and the
      insertion point of the screw in three dimensions on computed tomography scans.
      Based on these values, we measured the optimum screw insertion angle on sagittal
      and coronal planes, and the distance between the center and the posterior margin
      of the joint surface; our new hole-in-one guide was produced with these data.
      When the guide tip is determined to be located at the center posterior margin of
      the axial joint surface, and the guidewire insertion point is determined to be
      located at the center of the axial inferior facet immediately above the C2/3
      joint, the guidewire is passed through the axial pedicle and the center of the
      atlantoaxial joint. Since April 1997, we have used this hole-in-one guide
      technique in eight patients with atlantoaxial instability. The screws passed the
      pars interarticularis and the center of the atlantoaxial joint in all patients
      with safety and accuracy. No complications associated with this technique
      occurred.

PMID- 11289581
TI  - Reattachment of the greater trochanter using the Dall-Miles cable grip system in
      revision hip arthroplasty.
AB  - Clinical and radiographic results of trochanteric osteotomy after revision hip
      arthroplasty in 62 hips were reviewed. The osteotomized fragment had been
      reattached using the Dall-Miles cable grip system in each hip. The patients'
      average age at operation was 64.4 years (range, 40-86 years). The average
      duration of follow-up was 30.0 months (range. 12-60 months). Trochanteric
      nonunion was found in 19 hips (30.6%). Trochanteric nonunion developed in 14
      (38.9%) of 36 hips with each cable attached around the medial cortex bone, in 2
      (16.7%) of 12 hips with each cable passed in a drill hole, and in 3 (21.4%) of 14
      hips with one cable passed through a hole and the other attached around the
      medial cortex. Fragmentation developed in 18 hips (29.0%). In 3 of these 18, the
      fragments had migrated close to the acetabular component. Cable breakage was seen
      in 4 hips (6.5%), and bone absorption around the cable in the medial cortex was
      seen in 17 hips (27.4%). There were 16 hips (25.8%) that presented symptoms at
      the greater trochanter, including spontaneous pain and tenderness. When the Dall
      Miles cable grip device is used for reattachment of the greater trochanter,
      attention should be paid to the condition of the trochanteric bed, the tension of
      the abductor muscles, and to the placement of the cables and the H-shaped grip.

PMID- 11289582
TI  - Roles of the anterior cruciate ligament and the medial collateral ligament in
      preventing valgus instability.
AB  - Both the medial collateral ligament (MCL) and the anterior cruciate ligament
      (ACL) are reported to prevent valgus instability of the knee. In this study, the
      anatomical mechanisms by which these ligaments prevent valgus instability were
      experimentally investigated. The valgus rotation angle and the magnitude of the
      medial joint space opening were measured in six cadaveric knees, using biplanar
      photography before and after the MCL and/or the ACL were severed. A significant
      increase in the valgus rotation angle and a large medial joint space opening were
      observed when the MCL was severed. An increase in the valgus rotation angle was
      also observed when the ACL was severed, but only a small medial joint space
      opening was present. The increase in the valgus rotation angle after ACL
      severance was nearly parallel to the increase in the internal rotation of the
      tibia. Thus, we concluded that both ligaments function to prevent valgus
      instability, but that the anatomical reasons for their function are different.
      The MCL prevents valgus instability by stopping an opening in the medial joint
      space. The ACL, on the other hand, prevents the internal rotation of the tibia.
      When the ACL is severed, the internal rotation increases, and causes the valgus
      rotation angle to also increase, despite the presence of only a small medial
      joint space opening.

PMID- 11289583
TI  - Radiographic assessment of scapular rotational tilt in chronic shoulder
      impingement syndrome.
AB  - This study presents an objective evaluation of both scapular upward and axial
      rotational tilts in shoulder impingement syndrome, using a scapular spine line
      defined on antero-posterior (AP) radiographs of the shoulder as the referential
      line. Twenty-seven patients with unilateral shoulder motion pain, who were
      diagnosed as having chronic shoulder impingement syndrome, were enrolled in the
      study. Scapular upward and axial rotational tilts were compared between the
      affected and contralateral shoulders. AP radiographs were obtained at shoulder
      abduction angles of 0 degrees, 45 degrees, and 90 degrees, and the X-ray films
      were digitized by computer. The upward and axial rotational tilts of the scapula
      were then evaluated on the digital images. In shoulder impingement syndrome, both
      upward and axial external rotations of the scapula were impaired at the painful
      arc angle of abduction. This tended to be more apparent for the axial rotation of
      the scapula than for the upward rotation. These reductions in scapular rotations
      reduce available clearance for the rotator cuff and humeral greater tuberosity as
      the shoulder is abducted.

PMID- 11289584
TI  - Pressure distribution in the humeroradial joint and force transmission to the
      capitellum during rotation of the forearm: effects of the Sauve-Kapandji
      procedure and incision of the interosseous membrane.
AB  - A biomechanical study was undertaken, using four fresh cadaveric arms, to
      evaluate the changes in pressure distribution in the humeroradial joint (H-R
      joint) during rotation of the forearm before and after the Sauve-Kapandji
      procedure (S-K procedure) and also after incision of the interosseous membrane
      (IOM) following the S-K procedure. The pressure distribution was measured with a
      pressure-sensitive conductive rubber sensor while the forearm was rotated. Force
      transmitted to the capitellum was calculated from the measured pressure. In the
      intact specimens, pressure was concentrated on the medial side of the capitellum
      in pronation and on the posterolateral side in supination. The pattern of change
      after the S-K procedure and that after incision of the IOM following the S-K
      procedure were almost the same as that in the intact forearm. Although the force
      transmitted to the capitellum increased after the S-K procedure, there were no
      significant differences between the forces before and after the S-K procedure.
      However, the force increased significantly after incision of the IOM following
      the S-K procedure when the forearm was supinated more than 35 degrees, and it was
      concentrated on the posterior side of the capitellum. The IOM seemed to have an
      important axial load-bearing function in the forearm position supinated more than
      35 degrees. The S-K procedure in patients suffering from distal radioulnar joint
      disorders with IOM injury is likely to induce H-R joint osteoarthritis, so it
      should be avoided in these patients.

PMID- 11289585
TI  - Mechanical augmentation of the vertebral body by calcium phosphate cement
      injection.
AB  - The effectiveness of transpedicular calcium phosphate cement (CPC) injection as a
      new treatment for osteoporotic compression fracture of vertebrae was evaluated by
      measuring the compressive strength and the mode of failure in vertebrae
      experimentally injected with CPC. Forty-five human cadaver vertebrae were divided
      into three groups: a control group; group A, in which CPC was injected into the
      upper half of the vertebral body; and group B, in which CPC was injected into the
      whole vertebra. The load-displacement curve characteristically had two peaks in
      group A, and decreased rapidly after failure in group B. The failure site was the
      cancellous bone immediately below the cranial endplate in the control group,
      cancellous bone immediately below the CPC injection area in group A, and in the
      CPC injection area in group B. Although mechanical strength was greatest in those
      vertebrae in which the entire cancellous bone was replaced with CPC, the
      compressive strength of the vertebrae was also increased by partial replacement
      of cancellous bone with CPC injection. In terms of mode of failure and mechanical
      gradient with adjacent vertebrae, there were several advantages for those
      vertebrae in which the cranial half of the cancellous bone was replaced with CPC.

PMID- 11289586
TI  - Changes in dorsal horn neuronal responses in an experimental wrist contracture
      model.
AB  - Joint contracture, a major complication after casting, usually makes the
      therapeutic outcome worse by causing a limited range of motion and related pain.
      We developed rat models of wrist contracture with fracture of the radius (group
      A) and wrist contracture without fracture (group B), and investigated whether
      contracture and fracture changed the characteristics of cervical dorsal horn
      neuronal responses and the behavior of the animals. After 4 weeks of
      immobilization, both groups showed wrist contracture and disuse tendencies in the
      treated forelimb. In an electrophysiological study, the responses of 403 cervical
      dorsal horn neurons to mechanical stimuli were examined. In normal (control)
      animals, the neurons had the following distribution: 63% were low-threshold (LT);
      15% were high-threshold (HT); and 22% were wide-dynamic-range (WDR). In group A,
      the distribution of the neurons changed to 51% LT, 16% HT, and 33% WDR. Similar
      changes were observed for group B. Responses during wrist movement were also
      examined. Forty-one percent of cells in the control group were responsive to the
      movements, whereas the number of neurons responding to motion stimulus in both
      groups A and B was increased, to 77%. The changed population of WDR and LT
      neurons responding to wrist movement suggests that the characteristics of dorsal
      horn neurons may undergo plastic changes after contracture.

PMID- 11289587
TI  - Effect of particle size on macrophage-osteoclast differentiation in vitro.
AB  - To determine whether particle size affects macrophage-osteoclast differentiation
      in vitro, latex beads of 0.1, 1, and 10 microm in diameter were added to a murine
      macrophage-UMR106 osteoblast-like cell coculture system. The extent of osteoclast
      differentiation was determined by assessing the number of tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated cells on glass coverslips and the
      extent of lacunar resorption on dentine slices. The addition of particles, 1 and
      10microm in size, to the cocultures resulted in a significant increase in the
      number of TRAP-positive osteoclast-like cells and in the resorption pit surface
      area compared with findings in control cultures to which no particles had been
      added. Particles 0.1 microm in size also stimulated osteoclast formation relative
      to the control; however, the difference was not significant. These results
      indicate that particles, particularly these 1 and 10microm in size, sizes which
      were phagocytosable, significantly enhanced the process of macrophage-osteoclast
      differentiation and suggest that particle size plays an important role in
      periprosthetic osteolysis.

PMID- 11289588
TI  - Electrophysiological, histological, and behavioral studies in a cat with acute
      compression of the spinal cord.
AB  - We made an animal model of cervical spinal cord injury in a cat and performed
      electrophysiological, histological, and bechavioral studies. The cervical spinal
      cord injury model was made by inserting a screw through the fourth cervical
      vertebral body of the cat. After the injury, muscle tonus of the limbs and trunk
      diminished. The cat was able to walk and to perform target reaching after the
      injury, although the trunk was unstable and the movement of the forelimb was
      ataxic. Atrophy of the back muscle remained. The cat was unable to stand
      bipedally. These behavioral disturbances suggested dysfunction of the ventral
      funiculus. After behavioral analysis for 3 months, an electrophysiological study
      was performed. Action potentials of the ventral funiculus evoked by stimulation
      of the lateral vestibular nucleus or the medial longitudinal fasciculus were
      recorded at several levels of the cervical cord. They were diminished at levels
      caudal to the compression site. After the recording, the cervical cord was
      studied histologically. There was demyelination and gliosis in the ventral
      funiculus and in part of the ventrolateral funiculus at or near the injured site.
      Electrophysiological and histological findings were in good agreement with the
      behavioral ones. Behavioral studies seem useful for evaluating the function of
      the spinal cord, especially for assessing the injured system in the spinal cord.

PMID- 11289589
TI  - Semiquantitative analysis of types I and III collagen from tendons and ligaments
      in a rabbit model.
AB  - The present study presents a simple and reliable micro-method for the
      semiquantitative analysis of types I and III collagen in tendons and ligaments in
      a rabbit model. After pretreatment of the analytical material by homogenization,
      a double cyanogen bromide cleavage was performed and the peptide fragments were
      visualized by polyacrylamide gel electrophoresis and silvcr staining. On the
      basis of this procedure, the method presented here can be used to analyze very
      small amounts of sample material (less than 10microg) by electrophoresis. The
      results of the study showed that type I collagen is predominant in the ligaments
      and the tendons of the knee, e.g., medial and lateral collateral ligaments.
      anterior and posterior cruciate ligaments. patellar tendon, achilles tendon, and
      semitendinosus tendon. However, a markedly higher proportion of type III collagen
      was detected in the ligaments (approximately 10%) than in the tendons
      (approximately 5%). The ligaments differ markedly from the tendons in biochemical
      mapping; the ligaments are functionally and metabolically the more active tissue
      and have a higher adaptation potential.

PMID- 11289590
TI  - Cationic polymer-mediated genetic transduction into cultured human chondrosarcoma
      derived HCS-2/8 cells.
AB  - The usefulness of three types of cationic polymer, i.e., degraded polyamidoamine
      (PAMAM) dendrimer (SuperFect Transfection Reagent; Oiagen), linear
      polyethylenimine (PEI; ExGen 500; Euromedex), and branched PEI in gene delivery
      into chondrocytes was examined comparatively. A plasmid vector containing the
      Escherichia coli LacZ (pSES.beta) was combined with one of the three cationic
      polymers at various molar ratios and the resultant complex (polyplex) was used to
      transduce a human chondrocyte-like cell line, HCS-2/8. Gene expression was
      evaluated by an O-nitrophenyl beta-D-galactopyranoside (ONPG) assay and by
      staining with 0.05% 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal;
      Nacalai Tesque). The ONPG assay showed that the highest delivery rate was
      achieved when 2microg of pSES.beta was combined with either 21 microg of
      dendrimer, 1.7microg of linear PEI, or 2.0microg of branched PEI. At the same
      DNA/polymer ratios, the proportions of X-gal-stained cells were also the highest
      (31.3 +/- 7.5%, 30.3 +/- 9.0%, and 8.3 +/- 3.1%, respectively). LacZ expression
      reached the highest level 3 days after the dendrimer-mediated transduction, and
      gradually declined, returning to the background level on day 14. Possible
      cytotoxicity was examined by trypan blue staining and phase contrast microscopic
      observations. Neither cytotoxicity nor morphological change was induced at the
      optimal dose of each polymer. The cationic polymers, particularly the degraded
      dendrimer and linear PEI, would be a useful nonviral vector for gene delivery to
      cells of chondrocytes.

PMID- 11289591
TI  - Neurohistochemical analysis of regeneration in rat peripheral nerve after end-to
      side neurorrhaphy.
AB  - We investigated the regenerative capacity of motor nerves repaired by end-to-side
      or end-to-end neurorrhaphy, using choline-acetyltransferase (ChAT) activity
      measurement or histological analysis. The right medial gastrocnemius nerves
      (MGNs) of 62 male Fisher strain rats were transected and divided into three
      groups. In group 1, the distal ends of the MGN were coapted to the side of the
      lateral gastrocnemius nerve, using a Y-shaped silicone tube in end-to-side
      neurorrhaphy. In group 2, the nerve ends were reconnected by the traditional end
      to-end technique. In group 3, the nerve ends were separated and remained
      unrepaired. The MGNs were sampled 1, 2, and 3 months postoperatively for
      histological examinations and ChAT activity measurement. The medial gastrocnemius
      muscle (MGM) was also sampled for histological evaluations. Axonal regeneration
      of MGN and the recovery of MGM to nearly normal histology and weight were
      observed in groups 1 and 2 3 months postoperatively. Although there were no
      significant differences in ChAT values between groups 1 and 2, the values were
      significantly larger than that of group 3 3 months postoperatively. These
      findings suggested that end-to-side neurorrhaphy would be an alternative
      treatment for peripheral nerve injury in certain clinical situations.

PMID- 11289592
TI  - Extended posture of lumbar spine precipitating cauda equina compression arising
      from a postoperative epidural clot.
AB  - We report a patient with nonoperatively treated acute cauda equina compression
      arising from an epidural clot that developed after decompressive surgery for
      lumbar canal stenosis. A 43-year-old woman underwent lumbar laminotomy, and was
      symptom-free for 3 hours; but this was followed by paresis. Postoperative
      myelography showed obstruction of the contrast column at the level of the
      laminotomy; this was relieved by hyperflexion of the lumbar spine. With sustained
      hyperflexion of the lumbar spine, all neurologic deficits were completely
      resolved within 5 days. Lumbar lordosis may be present when a patient lies in the
      supine position on a flat bed with the hips and knees extended; this may
      exacerbate dural constriction caused by an epidural clot following posterior
      lumbar spinal surgery.

PMID- 11289593
TI  - Osteonecrosis of the femoral head that developed after long-term topical steroid
      application.
AB  - This is a report of a 52-year-old man who developed osteonecrosis of the femoral
      head (ONF) following long-term application of steroid for facial eczema. Before
      hip pain appeared, the patient had applied 2-3g/day of 0.05% clobetasol
      propionate for 2 years and 10 months. This steroid is classified as being in the
      strongest category. ONF was diagnosed based on radiographic and magnetic
      resonance imaging findings, and the patient received surgical treatment for both
      hips. ONF was also confirmed by pathological examination of a specimen obtained
      from the right femoral head during surgery. Because there were no risk factors
      for ONF besides topical steroid application, this case was considered as ONF
      associated with topical steroid. Even when steroids are for external use, their
      dosage and administration should be monitored, and the risk of ONF should also be
      considered.

PMID- 11289594
TI  - A myxoid liposarcoma in the lower leg, with a large intra-abdominal metastasis.
AB  - We report a patient with a large intra-abdominal metastasis of myxoid
      liposarcoma. The patient first noticed an asymptomatic mass in her left leg in
      1985, when she was 20 years old. The mass was left untouched until she realized
      its rapid growth and consulted a local doctor in 1994. After needle biopsy, she
      was histologically diagnosed as having a myxoid liposarcoma. She disagreed with
      the recommendation for an amputation below the knee, made at another hospital. A
      marginal resection was performed as an alternative treatment. She subsequently
      underwent three more marginal resections and four intra-lesional resections for
      repeated local recurrences. In 1997, an abdominal computed tomography scan
      revealed the presence of multiple intra-abdominal metastases, and the lesions
      were judged to be inoperable. Ileus and respiratory distress, caused by
      compression by the abdominal mass, gradually worsened, and she died in 1999, at
      the age of 34. The girth of her abdomen was 135 cm at the time of death.

PMID- 11289595
TI  - Accumulation of heavy metals in epidermal glands of the waterlily (Nymphaeaceae).
AB  - This study investigates the anatomical aspects of heavy-metal accumulation in the
      waterlily (Nymphaea 'Aurora', Nymphaeaceae). Epidermal glands were identified by
      light microscopy on the abaxial side of the leaf laminae and on the epidermis of
      the rhizome; glandular trichomes were observed in the petiole epidermis. Glands
      were not observed in the roots. Accumulation of heavy metals in these glands was
      monitored using a scanning electron microscope equipped for energy-dispersive
      spectroscopy. Further experiments showed maximal cadmium and calcium accumulation
      in the mature leaf lamina in daylight, and this accumulation was inhibited by the
      herbicide 3-(3',4'-dichlorophenyl)-1,1-dimethylurea. These results suggest that,
      in Nymphaea, heavy metals are accumulated primarily in association with glands
      found in plant organs that have direct contact with water or mud. Deposition and
      storage of heavy metals by these glands may represent a stage in the
      sequestration and detoxification of the metals. Our results raise the possibility
      of utilizing waterlilies for the removal of heavy metals from polluted
      environments.

PMID- 11289596
TI  - The involvement of polyphenols and peroxidase activities in heavy-metal
      accumulation by epidermal glands of the waterlily (Nymphaeaceae).
AB  - Co-localization of polyphenols and peroxidase activity was demonstrated in
      epidermal glands of the waterlily (Nymphaea) by histochemistry. Total phenols,
      tannins and peroxidase activity were determined quantitatively in plant extracts.
      Polyphenols were partially identified and were found to consist mainly of
      hydrolyzable tannins, gallic and tannic acid derivatives. Nymphaea polyphenols
      were shown to chelate Cr, Hg, and Pb in vitro, and Cd-binding by polymerized
      polyphenols was demonstrated in leaves exposed to Cd in vivo. Both polyphenols
      and peroxidases were found at very high constitutive levels, which were not
      induced or altered by external conditions, such as light and heavy-metal stress.
      It is suggested that the polymerization of polyphenols by peroxidases, enhanced
      after heavy-metal uptake and detoxification, is responsible for the binding of
      heavy metals in Nymphaea epidermal glands.

PMID- 11289597
TI  - Photoinactivation of photosystem II complexes and photoprotection by non
      functional neighbours in Capsicum annuum L. leaves.
AB  - Leaf segments from Capsicum annuum plants grown at 100 micromol photons m(-2) s(
      1) (low light) or 500 micromol photons m(-2) s(-1) (high light) were illuminated
      at three irradiances and three temperatures for several hours. At various times,
      the remaining fraction (f) of functional photosystem II (PS II) complexes was
      measured by a chlorophyll fluorescence parameter (1/Fo -1/Fm, where Fo and Fm are
      the fluorescence yields corresponding to open and closed PS II traps,
      respectively), which was in turn calibrated by the oxygen yield per saturating
      single-turnover flash. During illumination of leaf segments in the presence of
      lincomycin, an inhibitor of chloroplast-encoded protein synthesis, the decline of
      f from 1.0 to about 0.3 was mono-exponential. Thereafter, f declined much more
      slowly, the remaining fraction (approximately equals 0.2) being able to survive
      prolonged illumination. The results can be interpreted as being in support of the
      hypothesis that photoinactivated PS II complexes photoprotect functional
      neighbours (G. Oquist et al. 1992, Planta 186: 450-460), provided it is assumed
      that a photoinactivated PS II is initially only a weak quencher of excitation
      energy, but becomes a much stronger quencher during prolonged illumination when a
      substantial fraction of PS II complexes has also been photoinactivated. In the
      absence of lincomycin, photoinactivation and repair of PS II occur in parallel,
      allowing f to reach a steady-state value that is determined by the treatment
      irradiance, temperature and growth irradiance. The results obtained in the
      presence and absence of lincomycin are analysed according to a simple kinetic
      model which formally incorporates a conversion from weak to strong quenchers,
      yielding the rate coefficients of photoinactivation and of repair for various
      conditions, as well as gaining an insight into the influence off on the rate
      coefficient of photoinactivation. They demonstrate that the method is a
      convenient alternative to the use of radiolabelled amino acids for quantifying
      photoinactivation and repair of PS II in leaves.

PMID- 11289598
TI  - Modelling of auxin-binding protein 1 suggests that its C-terminus and auxin could
      compete for a binding site that incorporates a metal ion and tryptophan residue
      44.
AB  - Sequence comparison indicates that auxin-binding protein 1 (ABP1) belongs to a
      family of proteins with the core beta-barrel structure of the vicilins. Previous
      modelling within this family correctly predicted metal-ion binding and oligomeric
      properties of oxalate oxidase. ABP1 also contains a putative metal-ion-binding
      cluster of amino acids, adjacent to a tryptophan side chain, leading to a
      proposed auxin-binding site that incorporates metal-ion interaction with the
      auxin carboxylate. Modelling implicates W44 (Zea mays ABP1) in auxin binding,
      rather than W136 or W151. Reduced sequence similarity for the C-terminal region
      prevents model building. It is proposed that one of these C-terminal tryptophans,
      along with a neighbouring negatively charged side chain, occupies the binding
      pocket in the absence of auxin, thereby linking auxin binding to conformational
      change and C-terminal involvement in signalling.

PMID- 11289599
TI  - Altered pectin composition in primary cell walls of korrigan, a dwarf mutant of
      Arabidopsis deficient in a membrane-bound endo-1,4-beta-glucanase.
AB  - Korrigan (kor) is a dwarf mutant of Arabidopsis thaliana (L.) Heynh. that is
      deficient in a membrane-bound endo-1,4-beta-glucanase. The effect of the mutation
      on the pectin network has been studied in kor by microscopical techniques
      associated with various probes specific for different classes of pectic
      polysaccharides. The localisation of native crystalline cellulose was also
      examined using the cellobiohydrolase I-gold probe. The investigations were
      focused on the external cell walls of the epidermis, a cell layer that, in a
      number of plant species, has been shown to be growth limiting. Anionic sites
      associated with pectic polymers were quantified using the cationic gold probe.
      Homogalacturonans were quantified using polyclonal anti-polygalacturonic
      acid/rhamnogalacturonan I antibodies recognising polygalacturonic acid, and
      monoclonal JIM7 and JIM5 antibodies recognising homogalacturonans with a high or
      low degree of methyl-esterification, respectively. Rhamnogalacturonans were
      quantified with two monoclonal antibodies, LM5, recognising beta-1,4 galactan
      side chains of rhamnogalacturonan I, and CCRCM2. Our results show a marked
      increase in homogalacturonan epitopes and a decrease in rhamnogalacturonan
      epitopes in kor compared to the wild type. A substantial decrease in
      cellobiohydrolase I-gold labelling was also observed in the mutant cell walls.
      These findings demonstrate that a deficiency in an endo-1,4-beta-glucanase, which
      is in principle not directly implicated in pectin metabolism, can induce
      important changes in pectin composition in the primary cell wall. The changes
      indicate the existence of feedback mechanisms controlling the synthesis and/or
      deposition of pectic polysaccharides in primary cell walls.

PMID- 11289601
TI  - Preferential induction of a 9-lipoxygenase by salt in salt-tolerant cells of
      Citrus sinensis L. Osbeck.
AB  - Recent findings in our laboratory suggested that in citrus cells the salt
      induction of phospholipid hydroperoxide glutathione peroxidase, an enzyme active
      in cellular antioxidant defense, is mediated by the accumulation of
      hydroperoxides. Production of hydroperoxides occurs as a result of non-enzymatic
      auto-oxidation or via the action of lipoxygenases (LOXs). In an attempt to
      resolve the role of LOX activity in the accumulation of peroxides we analyzed the
      expression of this protein under stress conditions and in cells of Citrus
      sinensis L. differing in sensitivity to salt. Lipoxygenase expression was induced
      very rapidly only in the salt-tolerant cells and in a transient manner. The
      induction was specific to salt stress and did not occur with other osmotic-stress
      inducing agents, such as polyethylene glycol or mannitol, or under hot or cold
      conditions, or in the presence of abscisic acid. The induction was eliminated by
      the antioxidants dithiothreitol and kaempferol, thus once more establishing a
      correlation between salt and oxidative stresses. Analyses of both in vitro and in
      vivo products of LOX revealed a specific 9-LOX activity, and a very fast
      reduction of the hydroperoxides to the corresponding hydroxy derivatives. This
      suggests that one of the metabolites further downstream in the reductase pathway
      may play a key role in triggering defense responses against salt stress.

PMID- 11289600
TI  - Heat-stress induced synthesis  of chloroplast protein synthesis elongation factor
      (EF-Tu) in a heat-tolerant maize line.
AB  - A heat-tolerant maize (Zea mays L.) line, ZPBL 1304, synthesizes a unique set of
      five heat-shock polypeptides of 45 kDa. Previous studies suggested that these
      polypeptides might play a role in the development of thermotolerance in maize
      (Ristic et al., 1996, J. Plant Physiol. 149:424-432; Ristic et al., 1998, J.
      Plant Physiol. 153:497-505). In the present study, we isolated these
      polypeptides, sequenced them, and investigated their subcellular distribution and
      origin. Of the five polypeptides of 45 kDa, three polypeptides, including the two
      most abundant ones, yielded amino acid sequences similar to the chloroplast and
      bacterial protein synthesis elongation factor (EF-Tu). This was further confirmed
      using an antibody raised against maize EF-Tu, which showed a very strong reaction
      with the 45-kDa heatshock protein(s). Studies on subcellular distribution and
      origin revealed that the 45-kDa polypeptides were localized to the chloroplasts,
      and were likely of nuclear origin. A full-length maize EF-Tu cDNA (Zmeftu1),
      previously isolated from the B73 line of maize, was used as a probe for northern
      blot analysis of RNA extracted from the ZPBL 1304 maize line (the nucleotide and
      deduced amino acid sequences of Zmeftu1 are 88% identical to the rice EF-Tu
      sequence). Northern blots showed a 1.85-fold increase in steady-state levels of
      EF-Tu mRNA during heat stress. An increase in EF-Tu transcript levels during heat
      stress was accompanied by increased levels of the EF-Tu protein. Isolated
      chloroplasts from heat-stressed plants also had higher levels of EF-Tu as
      compared to control chloroplasts. The maize EF-Tu polypeptides showed > 80%
      sequence similarity with the bacterial EF-Tu, which has recently been shown to
      function as a molecular chaperone and to play a role in the protection of other
      proteins from thermal denaturation (Caldas et al., 1998, J. Biol. Chem. 273:11478
      11482). It is hypothesized that chloroplast EF-Tu of the ZPBL 1304 maize line
      plays an important role in the development of thermotolerance.

PMID- 11289602
TI  - Markers for oxidative stress associated with soft rots in French beans (Phaseolus
      vulgaris) infected by Botrytis cinerea.
AB  - The role of active oxygen species has been studied in spreading soft-rot lesions
      caused by the necrotrophic fungal pathogen Botrytis cinerea Pers.:Fr. in leaves
      of four genotypes of French bean (Phaseolus vulgaris L.). Large increases were
      observed for the aldehydic end-products of oxidative damage, malondialdehyde and
      4-hydroxy-2-nonenal, as a result of infection in each of the genotypes studied.
      Similar increases were found in a stable free radical and g=4.27 Fe(III) signals,
      but not Mn(II) signals, in electron paramagnetic resonance spectra. These changes
      were accompanied by large decreases in ascorbic acid levels, with changes in the
      antioxidant glutathione being genotype dependent.

PMID- 11289603
TI  - Xanthophyll synthesis in diatoms: quantification of putative intermediates and
      comparison of pigment conversion kinetics with rate constants derived from a
      model.
AB  - Recently, we reported the presence of the violaxanthin-antheraxanthin-zeaxanthin
      cycle in diatoms, and showed that violaxanthin is the putative precursor of both
      diadinoxanthin and fucoxanthin in the diatom Phaeodactylum tricornutum Bohlin (M.
      Lohr and C. Wilhelm, 1999, Proc. Natl. Acad. Sci. USA 96: 8784-8789). In the
      present study, two possible intermediates in the synthesis of violaxanthin from
      beta-carotene were identified in P. tricornutum, namely beta-cryptoxanthin and
      beta-cryptoxanthin epoxide. In low light, the latter pigment prevails, but in
      high light beta-cryptoxanthin accumulates, probably as the result of an increased
      activity of the xantophyll-cycle de-epoxidase. The apparent kinetics of several
      xanthophyll conversion steps were determined for P. tricornutum and Cyclotella
      meneghiniana Kuitzing. The experimentally determined conversion rates were used
      to evaluate the hypothetical pathway of xanthophyll synthesis in diatoms. For
      this purpose a mathematical model was developed which allows the calculation of
      theoretical rates of pigment conversion for microalgae under steady-state growth
      conditions. A comparison between measured and calculated conversion rates agreed
      well with the proposal of a sequential synthesis of fucoxanthin via violaxanthin
      and diadinoxanthin. The postulation of zeaxanthin as an obligatory intermediate
      in the synthesis of violaxanthin, however, resulted in large discrepancies
      between the measured and calculated rates of its epoxidation. Instead of
      zeaxanthin, beta-cryptoxanthin epoxide may be involved in the biosynthesis of
      violaxanthin in diatoms.

PMID- 11289604
TI  - Demonstration of prominent actin filaments in the root columella.
AB  - The distribution of actin filaments within the gravity-sensing columella cells of
      plant roots remains poorly understood, with studies over numerous years providing
      inconsistent descriptions of actin organization in these cells. This uncertainty
      in actin organization, and thus in actin's role in graviperception and
      gravisignaling, has led us to investigate actin arrangements in the columella
      cells of Zea mays L., Medicago truncatula Gaertn., Linum usitatissiilium L. and
      Nicotianla benthamiana Domin. Actin organization was examined using a combination
      of optimized immunofluorescence techniques, and an improved fluorochrome
      conjugated phalloidin labeling method reliant on 3-maleimidobenzoyl-N-hydroxy
      succinimide ester (MBS) cross-linking combined with glycerol permeabilization.
      Confocal microscopy of root sections labeled with anti-actin antibodies revealed
      patterns suggestive of actin throughout the columella region. These patterns
      included short and fragmented actin bundles, fluorescent rings around amyloplasts
      and intense fluorescence originating from the nucleus. Additionally, confocal
      microscopy of MBS-stabilized and Alexa Fluor-phalloidin-labeled root sections
      revealed a previously undetected state of actin organization in the columella.
      Discrete actin structures surrounded the amyloplasts and prominent actin cables
      radiated from the nuclear surface toward the cell periphery. Furthermore, the
      cortex of the columella cells contained fine actin bundles (or single filaments)
      that had a predominant transverse orientation. We also used confocal microscopy
      of plant roots expressing endoplasmic reticulum (ER)-targeted green fluorescent
      protein to demonstrate rapid ER movements within the columella cells, suggesting
      that the imaged actin network is functional. The successful identification of
      discrete actin structures in the root columella cells forms the perception and
      signaling.

PMID- 11289605
TI  - Proteomic analysis reveals a novel set of cell wall proteins in a transformed
      tobacco cell culture that synthesises secondary walls as determined by
      biochemical and morphological parameters.
AB  - A cell suspension culture of a tobacco (Nicotiana tabacum L. cv. Petit Havana)
      cell line derived from a cultivar transformed with the Tcyt gene from
      Agrobacterium, which leads to high endogenous levels of cytokinin, has been
      established. This cell line shows increased cell aggregation, elongated cells and
      a 5-fold increase in wall thickness. If allowed to carry on growing it can form a
      single mass without shedding cells into the medium. When analysed at an earlier
      growth stage, these cultures were found to produce improved levels of vascular
      nodule formation than in other systems that employ exogenous cytokinin. This
      differentiation was optimised with respect to sucrose and auxin signals in order
      to induce maximum production of cells with thickened walls and a morphology
      characteristic of fibre cells and tracheids, in addition to cells that remain
      meristematic. In order to establish the validity of this system for studying
      secondary wall formation, the walls and associated biosynthetic changes were
      analysed in these cells by chemical analysis of the walls, changes in activities
      of enzymes of xylan and monolignol synthesis, and expression of mRNAs coding for
      enzymes of lignin biosynthesis. The wall composition of the transformed cells was
      compared with that determined for primary walls from a typical untransformed
      tobacco cell line. Recovery of wall material was 50% greater in the transformed
      culture. In this material a major difference was found in the pectin fraction
      where there was a distinct difference in size distribution together with a lower
      level of methylation for the transformed line, which may be related to increased
      adhesiveness. There were increased amounts of xylan, although the ratio of
      xyloglucan to xylan content was not substantially different due to the mixture of
      cell types. There was also an increase in cellulose and phenolic components.
      Increased activity of enzymes involved in the synthesis of xylan as a marker for
      the secondary wall occurred around the time of tracheid differentiation and
      coincided with a broad peak of cinnamyl alcohol dehydrogenase activity. The
      expression of mRNAs coding for enzymes of the general phenylpropanoid pathway,
      phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, catechol O-methyl
      transferase was relatively constitutive in the cultures while transcripts of
      ferulate 5-hydroxylase, cinnamoyl CoA-reductase, cinnamyl alcohol dehydrogenase
      and lignin peroxidase were induced. The walls of the transformed cells also
      showed considerable differences in the subset of extractable proteins from that
      found in primary walls of tobacco when these were subjected to proteomic
      analysis. Many of these proteins appear to be novel and not present in primary
      walls. However an Mr-32,000 chitinase, an Mr-34,000 peroxidase, an Mr-65,000
      polyphenoloxidase/laccase and possibly an Mr-68,000 xylanase could be identified
      as well as structural proteins.

PMID- 11289607
TI  - Red-light-induced positive phototropism in Arabidopsis roots.
AB  - The interaction between light and gravity is critical in determining the final
      form of a plant. For example, the competing activities of gravitropism and
      phototropism can determine the final orientation of a stem or root. The results
      reported here indicate that, in addition to the previously described blue-light
      dependent negative phototropic response in roots, roots of Arahidopsis thaliana
      (L.) Heynh. display a previously unknown red-light-dependent positive phototropic
      response. Both phototropic responses in roots are considerably weaker than the
      graviresponse, which often masks phototropic curvature. However, through the use
      of mutant strains with impaired gravitropism, we were able to identify a red
      light-dependent positive phototropic response in Arabidopsis roots. The red
      induced positive phototropic response is considerably weaker than the blue-light
      response and is barely detectable in plants with a normal gravitropic response.

PMID- 11289606
TI  - Chlorophyta exclusively use the 1-deoxyxylulose 5-phosphate/2-C-methylerythritol
      4-phosphate pathway for the biosynthesis of isoprenoids.
AB  - The biosynthesis of the C5 building block of isoprenoids, isopentenyl diphosphate
      (IPP), proceeds in higher plants via two basically different pathways; in the
      cytosolic compartment sterols are formed via mevalonate (MVA), whereas in the
      plastids the isoprenoids are formed via the 1-deoxyxylulose 5-phosphate/2-C
      methylerythritol 4-phosphate pathway (DOXP/MEP pathway). In the present
      investigation, we found for the Charophyceae, being close relatives to land
      plants, and in the original green flagellate Mesostignma virilde the same IPP
      biosynthesis pattern as in higher plants: sterols are formed via MVA, and the
      phytol-moiety of chlorophylls via the DOXP/MEP pathway. In contrast,
      representatives of four classes of the Chlorophyta (Chlorophyceae, Ulvophyceae,
      Trebouxiophyceae, Prasinophyceae) did not incorporate MVA into sterols or phytol.
      Instead, they incorporated [1-2H1]-1-deoxy-D-xylulose into phytol and sterols.
      The results indicate that the entire Chlorophyta lineage, which is well separated
      from the land plant/Charophyceae lineage, is devoid of the acetate/ MVA pathway
      and uses the DOXP/MEP pathway not only for plastidic, but also for cytosolic
      isoprenoid formation.

PMID- 11289608
TI  - Induction of wound response gene expression in tomato leaves by ionophores.
AB  - Three ionophores were used to investigate a potential role of the plasma-membrane
      (PM) potential in the regulation of systemic wound-response gene expression in
      tomato (Lycopersicon escuilentum Mill.) plants. Valinomycin, nigericin, and
      gramicidin, which affect the PM potential by dissipating H+ and K+ gradients,
      respectively, induced the rapid accumulation of wound-response gene transcripts.
      Transcript induction by gramicidin was kinetically, qualitatively and
      quantitatively similar to systemin-induced transcript accumulation. On a molar
      basis, gramicidin and nigericin, which affect gradients of both H+ and K+, were
      more effective than the K+-selective valinomycin. Hyperpolarization of the PM by
      fusicoccin, on the other hand, repressed wound-response gene expression and, at
      the same time, induced salicylic acid (SA) accumulation and the expression of
      pathogenesis-related proteins. We show here that the inhibition of the wound
      response after fusicoccin treatment is not mediated by elevated concentrations of
      SA but is likely a direct effect of PM hyperpolarization. The data indicate a
      role for the PM potential in the differential regulation of wound and pathogen
      defense responses.

PMID- 11289610
TI  - Replication and G2 checkpoints: their response to caffeine.
AB  - Under long hydroxyurea treatments, evidence was obtained for the sequential
      activation of four checkpoints located between the onset of S phase and mitosis
      in Allium cepa L. root meristems. Biparametric flow cytometry (Br-DNA/total DNA)
      showed that cells initially accumulated at early S phase but, after a delay, they
      resumed replication and paused again at mid S phase. Cells not only overrode this
      second replication block but also any G2 checkpoint they encountered. Thus, a
      late mitotic wave was produced in the presence of hydroxyurea. The wave was
      formed by cells that had apparently completed their replication (normal mitoses),
      while others displayed anaphases/telophases with less than the expected DNA
      content and with chromosomal breaks (aberrant mitoses). The presence of aberrant
      mitoses is direct evidence for the undue override of the two G2 checkpoints
      responsible for surveillance of completion of DNA synthesis and repair,
      respectively. Caffeine selectively abrogated the G2 block produced by the
      checkpoint that controls post-replication DNA repair, as it advanced the entry of
      cells into an aberrant mitosis. However, caffeine proved not to be the universal
      checkpoint-evading agent as postulated. Caffeine did not modify the spontaneous
      override of the replication checkpoints. Moreover, it seems to enforce the
      checkpoint that controls the completion of DNA synthesis, as the appearance of
      the late wave of normal mitoses produced in the presence of hydroxyurea was
      prevented by the use of caffeine.

PMID- 11289609
TI  - Sucrose assimilation during early developmental stages of chicory (Cichorium
      intybus L.) plants.
AB  - The activities of enzymes of both sucrose and fructan metabolism were measured in
      chicory (Cichorium intybus L. cv. Turbo) plants during early vegetative growth.
      From 21 to 42 d after sowing (phase I), carbohydrates were used for structural
      growth and sucrose was predominantly cleaved by acid invertase whereas neutral
      invertase (EC 3.2.1.26) and sucrose synthase (EC 2.4.1.13) activities were low.
      From 49 to 63 d after sowing (phase II) a cambium formed producing secondary
      tissues, concomitant with induced sucrose:sucrose 1-fructosyl transferase (1-SST;
      EC 2.4.1.99) and fructan:fructan-1-fructosyl transferase (EC 2.4.1.100)
      activities, and fructan synthesis in the roots. Accumulation of 1-SST mRNA
      occurred at the onset of thickening, indicating that 1-SST is controlled at a
      transcriptional level. Acid invertase activity gradually increased during phase I
      and remained high during early phase II. It subsequently decreased. The pattern
      of invertase mRNA accumulation correlated with the enzyme activities, indicating
      that acid invertase is controlled at the transcriptional level. Both acid
      invertase and 1-SST probably contributed to the sink strength in the root at the
      beginning of phase II.

PMID- 11289611
TI  - Identification and localization of a thylakoid-bound carbonic anhydrase from the
      green algae Tetraedron minimum (Chlorophyta) and Chlamydomonas noctigama
      (Chlorophyta).
AB  - In order to broaden our understanding of the eukaryotic CO2-concentrating
      mechanism the occurrence and localization of a thylakoid-associated carbonic
      anhydrase (EC 4.2.1.1) were studied in the green algae Tetraedron minimum and
      Chlamydomonas noctigama. Both algae induce a CO2-concentrating mechanism when
      grown under limiting CO2 conditions. Using mass-spectrometric measurements of 18O
      exchange from doubly labelled CO2, the presence of a thylakoid-associated
      carbonic anhydrase was confirmed for both species. From purified thylakoid
      membranes, photosystem I (PSI), photosystem II (PSII) and the light-harvesting
      complex of the photosynthetic apparatus were isolated by mild detergent gel. The
      protein fractions were identified by 77 K fluorescence spectroscopy and
      immunological studies. A polypeptide was found to immunoreact with an antibody
      raised against thylakoid carbonic anhydrase (CAH3) from Chlamydomonas
      reinhardtii. It was found that this polypeptide was mainly associated with PSII,
      although a certain proportion was also connected to light harvesting complex II.
      This was confirmed by activity measurements of carbonic anhydrase in isolated
      bands extracted from the mild detergent gel. The thylakoid carbonic anhydrase
      isolated from T. minimum had an isoelectric point between 5.4 and 4.8. Together
      the results are consistent with the hypothesis that thylakoid carbonic anhydrase
      resides within the lumen where it is associated with the PSII complex.

PMID- 11289612
TI  - Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in
      the biosynthetic pathway of the novel antimalarial drug artemisinin.
AB  - The sesquiterpenoid artemisinin, isolated these from the plant Artemisia annua
      L., and its semi-synthetic derivatives are a new and very effective group of
      antimalarial drugs. A branch point in the biosynthesis of this compound is the
      cyclisation of the ubiquitous precursor farnesyl diphosphate into the first
      specific precursor of artemisinin, namely amorpha-4,11-diene. Here we describe
      the isolation of a cDNA clone encoding amorpha-4,11-diene synthase. The deduced
      amino acid sequence exhibits the highest identity (50%) with a putative
      sesquiterpene cyclase of A. annua. When expressed in Escherichia coli, the
      recombinant enzyme catalyses the formation of amorpha-4,11-diene from farnesyl
      diphosphate. Introduction of the gene into tobacco (Nicotiana tabacum L.)
      resulted in the expression of an active enzyme and the accumulation of amorpha
      4,11-diene ranging from 0.2 to 1.7 ng per g fresh weight.

PMID- 11289613
TI  - Cortical actin filaments in guard cells respond differently to abscisic acid in
      wild-type and abi1-1 mutant Arabidopsis.
AB  - Cortical actin filaments in guard cells of Commelina communis L. show signal
      specific organization during stomatal movements [S.-O. Eun and Y. Lee (1997)
      Plant Physiol 115: 1491-1498; S.-O. Eun and Y. Lee (2000) Planta 210: 1014-1017].
      To study the roles of actin in signal transduction, it is advantageous to use
      Arabidopsis thaliana (L.) Heynh., an excellent model plant with numerous well
      characterized mutants. Using an immunolocalization technique, we found that actin
      deployments in guard cells of A. thaliana were basically identical to those in C.
      communis: actin proteins were assembled into radial filaments under illumination,
      and were disassembled by ABA. In addition, we examined actin organization in an
      ABA-insensitive mutant (abi1-1) to test the involvement of protein phosphatase 2C
      (PP2C) in the control of actin structure. A clear difference was observed after
      ABA treatment, namely, neither stomatal closing nor depolymerization of actin
      filaments was observed in guard cells of the mutant. Our results indicate that
      PP2C participates in ABA-induced actin changes in guard cells.

PMID- 11289614
TI  - Enzymic feruloylation of arabinoxylan-trisaccharide by feruloyl-CoA:arabinoxylan
      trisaccharide O-hydroxycinnamoyl transferase from Oryza sativa.
AB  - Feruloyl-CoA:arabinoxylan-trisaccharide O-hydroxycinnamoyl transferase, which
      catalyzes the transfer of ferulic acid from Fer-CoA to arabinoxylan-trisaccharide
      in the formation of feruloyl arabinoxylan-trisaccharide (Fer-AXX), has been found
      in an ionically bound fraction and a cytosol fraction of suspension-cultured rice
      (Oriza sativa L. cv. Nipponbare) cells. Analysis of reaction products by high
      performance liquid chromatography showed the formation of product A, which is one
      of the transfer products having the same retention time as authentic Fer-AXX.
      Product A was purified by reverse-phase chromatographies to characterize its
      structure. The isolated product A showed the same ultraviolet spectrum and
      molecular weight on fast atom bombardment mass spectrometric analysis as those of
      authentic Fer-AXX. Alakaline saponification of product A released ferulic acid
      and oligosaccharide. The released oligosaccharide consisted of arabinose and
      xylose in a molar ratio of 1:2. These results support the identity of product A
      as feruloylated arabinoxylan-trisaccharide and show the existence of a
      feruloyltransferase catalyzing the feruloylation of a hemicellulosic fragment.

PMID- 11289615
TI  - Long-term follow-up on keratocysts treated according to a defined protocol.
AB  - A prospective study was conducted on 82 odontogenic keratocysts (OKCs) diagnosed
      in 80 patients over a 25 year period. The clinical and radiographic data were
      correlated, which resulted in an accurate picture of the clinical presentation,
      relationship with teeth and incidence of lingual perforations in mandibular OKCs.
      In 40% of the cysts no suspicion had arisen before surgery, in 60% the diagnosis
      was secured before surgery. This last group of patients was treated according to
      a defined protocol, with the exception of the maxillary OKCs, which entailed
      excision of the attached, overlying mucosa and enucleation of the cyst after
      which the defect was treated with Carnoy's solution. The other patients underwent
      just enucleation of the cysts. For the first 5 years the patients were seen every
      year, thereafter every 2 years if possible. Recurrences (9/82) were mainly found
      in the patients in which the cyst had just been enucleated. Only three cysts
      recurred in the group treated according to the above mentioned protocol. Most
      recurrences presented within 5 years, but late recurrences did occur even after
      25 years. The aetiology and pathogenesis of OKCs is briefly discussed in the
      light of the present findings. It is concluded that the suggested treatment
      protocol and follow-up schedule provides a safe means to manage a lesion that is
      known to recur and may even give rise to life threatening situations.

PMID- 11289616
TI  - Computer assisted oral and maxillofacial surgery--a review and an assessment of
      technology.
AB  - Advances in the basic scientific research within the field of computer assisted
      oral and maxillofacial surgery have enabled us to introduce features of these
      techniques into routine clinical practice. In order to simulate complex surgery
      with the aid of a computer, the diagnostic image data and especially various
      imaging modalities including computer tomography (CT), magnetic resonance imaging
      (MRI) and Ultrasound (US) must be arranged in relation to each other, thus
      enabling a rapid switching between the various modalities as well as the viewing
      of superimposed images. Segmenting techniques for the reconstruction of three
      dimensional representations of soft and hard tissues are required. We must
      develop ergonomic and user friendly interactive methods for the surgeon, thus
      allowing for a precise and fast entry of the planned surgical procedure in the
      planning and simulation phase. During the surgical phase, instrument navigation
      tools offer the surgeon interactive support through operation guidance and
      control of potential dangers. This feature is already available today and within
      this article we present a review of the development of this rapidly evolving
      technique. Future intraoperative assistance takes the form of such passive tools
      for the support of intraoperative orientation as well as so-called 'tracking
      systems' (semi-active systems) which accompany and support the surgeons' work.
      The final form are robots which execute specific steps completely autonomously.
      The techniques of virtual reality and computer assisted surgery are increasingly
      important in their medical applications. Many applications are still being
      developed or are still in the form of a prototype. It is already clear, however,
      that developments in this area will have a considerable effect on a surgeon's
      routine work.

PMID- 11289617
TI  - Intraoperative computed tomography with the mobile CT Tomoscan M during surgical
      treatment of orbital fractures.
AB  - Up to now it has only been possible to monitor the alignment of orbital floor
      fractures postoperatively with a computed tomography (CT) examination with
      coronal sectioning. If this showed an incorrect positioning, renewed surgery and
      anaesthetics were often required. The purpose of this study was the
      implementation and definition of the spectrum of indications for intraoperative
      CT examinations while keeping patient radiation exposure to a minimum. Thirty-two
      orbital fracture cases were examined pre- and intraoperatively using the mobile
      computer tomograph Tomoscan M in coronal sectioning. In this patient collective,
      12 cases showed an isolated orbital floor fracture and twenty cases an orbital
      floor fracture associated with a zygomatic fracture. The technical prerequisite
      for these examinations was the construction of a suitable radiolucent operating
      table which permitted coronal sections to be made with the CT-Gantry tilted. The
      authors aimed to reduce radiation exposure by optimizing the technical setting
      parameters and closely defining the scan region for the operator. In three of 32
      cases there were no surgical indications following clinical and preoperative CT
      examination. In three of the 20 cases with associated zygomatic fracture a closed
      reduction with a reduction hook was carried out, and no revision was necessary
      after the intraoperative CT examination. In 26 cases an open reduction was
      carried out. Of these open reduced fractures, four had to be revised after
      intraoperative CT monitoring; one of the isolated orbital floor fractures and
      three of those associated with a zygomatic fracture. Intraoperative CT monitoring
      of orbital floor fractures is considered a useful surgical aid. Its advantages
      are immediate monitoring of the surgical reduction, the presence of the surgeon
      during scanning enabling him to determine directly the relevant sections to scan,
      and the resulting radiation exposure.

PMID- 11289618
TI  - The use of acrylic marbles for interposition arthroplasty in the treatment of
      temporomandibular joint ankylosis: follow-up of 47 cases.
AB  - This is a retrospective analysis of 47 patients (21 males, 26 females) with
      osseous or fibro-osseous temporomandibular joint ankylosis. who were referred to
      our clinic between 1981 and 1998. In all cases, an acrylic marble was used as the
      interpositional material to prevent recurrence after aggressive resection of the
      ankylotic mass. The mean mouth opening was 15.65 mm preoperatively and 32.48 mm
      postoperatively. Complications during the follow-up period, which ranged from 1
      to 17 years, included reankylosis in three cases and extrusion and displacement
      of the acrylic marbles in two cases. The method produced good results and we
      believe that it is a simple alternative to other interposition arthroplasty
      procedures. Moreover, it has the advantages of reducing operating time and not
      requiring any personal skill.

PMID- 11289619
TI  - Suprafascial dissection of the radial forearm flap and donor site morbidity.
AB  - A cutaneous free radial forearm flap was harvested from 25 patients using a
      suprafascial dissection technique. The donor site was managed with either a full
      or split thickness skin graft and a negative pressure wound dressing. The
      incidence of initial complete graft take was 96% at day 5 and 100% by 1 month.
      There was 100% early and complete graft take in the full thickness group but one
      area of partial loss in the split thickness group. This area of graft loss
      represented less than 0.5% of the total grafted area in this series. The mean
      time to wound healing was 14 days. There were no cases of tendon exposure or
      delayed healing. The suprafascial dissection creates a superior graft recipient
      bed. When combined with the negative pressure wound dressing technique it ensured
      early and complete graft take.

PMID- 11289620
TI  - Aesthetic and functional results of harvesting radial forearm flap, especially
      with regard to hand function.
AB  - There is controversy in the literature regarding donor site morbidity following
      radial forearm flap harvesting. The aim of this study was to verify possible
      functional and aesthetic impairments at the donor site. Thirty-five patients who
      underwent maxillofacial reconstruction using radial forearm flap were asked to
      give their subjective assessment of the aesthetic outcome at the donor site and
      of postoperative hand function. They were also examined for trophic status; cold
      intolerance and tactile sensitivity of split-thickness skin graft, palm and
      finger pads; grip strength and finger-to-thumb pinch strength; range of movement
      for the wrist and finger joints; as well as functional hand testing. Slight
      impairments regarding hand strength and mobility were observed. However, due to
      their small extent they were of no clinical relevance, as shown by 85.7% of our
      patients displaying optimal functional hand testing values (80-100%), and 88.6%
      giving a positive subjective assessment (80-100%) of postoperative vs
      preoperative hand function. The results show that donor site morbidity following
      radial forearm flap harvesting is low.

PMID- 11289621
TI  - Development of squamous cell carcinoma from pre-existent oral leukoplakia: with
      respect to treatment modality.
AB  - The present study was undertaken in order to determine whether surgical treatment
      of oral leukoplakia reduces the risk of the subsequent development of carcinoma.
      This study included 142 patients with oral leukoplakia who received or did not
      receive surgical treatment. All subjects were followed-up for more than 6 months
      with a mean follow-up period of 4 years. Malignant transformation rate was lower
      among patients who received surgical excision (1/75) than among those who did not
      receive surgical treatments (4/51). However, the malignant transformation rates
      were high in patients who received cryosurgery (3/12) or cryosurgery plus
      surgical excision (1/4). There was no obvious relation between the grade of
      epithelial dysplasia and the rate of malignant transformation. Our results
      suggest that surgical excision of oral leukoplakia may reduce the risk of the
      subsequent development of carcinoma.

PMID- 11289622
TI  - Radiographic follow-up of impacted third molars from age 20 to 32 years.
AB  - Nineteen patients (13 male, six female) with 34 impacted third molars, 21 in the
      mandible and 13 in the maxilla were radiographically followed from age 20 to 32.
      All were examined clinically and panoramic radiographs were taken at baseline and
      at the end of the study. Radiographic analysis included resorption of teeth,
      enlargement of the follicle, development of the root, change in inclination of
      the third molar, state of impaction, relative depth of the third molar in bone
      and relation to the ramus of the mandible and to the second molar tooth. In the
      mandible, the mean change in inclination was 19 degrees and the percentage of
      teeth with changed angulation was 76%. In the maxilla, only 23% of the teeth
      changed their inclination. The state of impaction (soft tissue, partially in
      bone, completely in bone) had changed for 44% of the teeth. According to the
      questionnaire, no pain or symptoms in the region of the third molars were
      reported by 74% of the students during the 12-year period. It is concluded that
      considerable radiographic changes, without notable symptoms, may occur involving
      inclination of the tooth and state of impaction in impacted third molars after
      the usual age of eruption.

PMID- 11289623
TI  - Comparative study of three different membranes for guided bone regeneration of
      rat cranial defects.
AB  - The purpose of the study was to compare the efficacy of a non-resorbable
      polytetrafluoroethylene (e-PTFE) membrane (Gore-Tex) versus a resorbable
      polyglactin membrane (Vicryl) and a newly designed collagenic membrane for
      enhancing bone regeneration on rat skull defects. The study was conducted on 30
      adult Wistar rats. On each animal, two symmetrical, 6 mm wide, full-thickness,
      skull defects were created in the parietal regions. The right defect was chosen
      as the experimental site and the left one was left empty as a control. Each
      experimental site was covered by an inner and outer membrane. The 30 rats were
      divided into three groups: In group 1 (n=10), a non-resorbable
      polytetrafluoroethylene (e-PTFE) membrane was used. In group 2 (n= 10), a
      resorbable polyglactin 910 membrane was used. In group 3 (n= 10), a collagen
      membrane processed from avian eggshell was used. In each group, the animals were
      euthanized at 60 days. The harvested specimens were processed for contact
      radiography and standard histological examination. The results were assessed by a
      Fisher's exact test. In group 1, partial bone healing was observed in seven out
      of 10 animals and complete in three out of 10 animals (P<0.001). In group 2, no
      or minimal bone healing was observed in seven out of 10 animals and partial bone
      healing was observed in three out of 10 animals. In group 3, no or minimal bone
      healing was observed in nine out of 10 cases and partial bone healing in only one
      animal. In conclusion, only the non-resorbable e-PTFE membrane group exhibited a
      favourable result in this study. This study suggests that the structure of the
      membrane is at least as important as its composition.

PMID- 11289624
TI  - Experimental model for transplantation of a modified free myocutaneous gracilis
      flap to an irradiated neck region in rats.
AB  - In 102 Wistar rats (male, weight 300-500 g), a modified free myocutaneous
      gracilis flap was obtained from the groin and transplanted to the neck. To create
      a pre-irradiated transplant bed, a local area of the neck was irradiated
      preoperatively with 30 Gy (fractionation: 3 x 10 Gy) in 30 animals, and with 50
      Gy (fractionation: 5 x 10 Gy) in a further 30 animals. The interval between
      preoperative irradiation and transplantation was 4 weeks. Forty-two animals
      received no such preoperative radiation. The evaluation of healing and the
      success of the transplanted flap was based on a clinical assessment, carried out
      on postoperative days 1 7. Testing for significant differences was done
      nonparametrically using the Kruskal-Wallis test. The survival rate in the
      nonirradiated animals was 86%. In contrast, the healing of the free flaps in the
      pre-irradiated transplant bed was significantly lower (P=0.003) 76%, after
      irradiation with 30 Gy and 50% after 50 Gy. The significant difference (P=0.020)
      in survival rates after irradiation with 30 and 50 Gy was evidence for the
      dependence of successful healing on the preoperative radiation dose.
      Transplantation of the free myocutaneous gracilis flap to a previously irradiated
      transplant bed in the region of the neck is a suitable model for investigating
      the healing of free transplants to irradiated tissue. The success rate observed
      in non-irradiated transplant beds is comparable to that seen with other flap
      models in rats.

PMID- 11289626
TI  - Complete  bony fusion of the mandible to the zygomatic complex and maxillary
      tuberosity: case report and review.
AB  - Congenital craniofacial disorders represent approximately 20% of all birth
      defects. One of these disorders is syngnathia, of which only 24 cases have been
      reported since 1936. Twenty cases involved fusion of the alveolar processes of
      the maxilla and mandible. Only four are similar to the presented case, which
      includes bony fusion of the ascending ramus of the mandible to the zygomatic
      complex and the posterior part of the maxilla. This case report will present
      details from the 23rd week of gestation to 8 months of age when the infant
      underwent the first attempt to free the syngnathia. The literature is discussed
      and a causative mechanism and new classification are proposed.

PMID- 11289625
TI  - The effect of streptozotocin-induced experimental diabetes mellitus on calvarial
      defect healing and bone turnover in the rat.
AB  - Tooth socket healing is delayed in diabetes mellitus due to impairment of the
      healing process. One reason for the poor healing may be an abnormal vascular
      response. The object of our experiments was to study the effect of diabetes
      mellitus on bone healing using a calvarial wound. Streptozotocin, injected
      intraperitoneally, was used to induce diabetes in rats. Both insulin-treated,
      streptozotocin-dosed animals and normal rats were used as controls. Bone
      formation was measured in the diabetic femur and tibia, and healing of bone
      defects by guided tissue regeneration was assessed. Cancellous bone volume and
      bone formation in the femur were greatly reduced in the diabetic model,
      indicating either a defect of mineralization or osteoid formation. The length,
      dry weight, ash weight and calcium content of the tibiae of diabetic rats were
      significantly less than those of the control groups. In a second experiment, a
      sterile wound was made in the calvaria of diabetic rats, and covered internally
      and externally with Gore-Tex membrane. Exuberant formation of a primitive bone
      was evident, with little evidence of osteoclastic resorption of the necrosed bone
      ends. This was despite the impaired bone formation observed in the long bones in
      the first experiment.

PMID- 11289627
TI  - Longitudinal in vivo observations on odontogenic keratocyst over a period of 4
      years.
AB  - A case is presented of simultaneous adjacent odontogenic keratocyst and
      dentigerous cyst occurring in the same quadrant. Their in vivo behaviour,
      influence and effect on each other, surrounding tissues and on tooth development
      over a period of 4 years are described. This unique case may further advance the
      understanding of the behaviour of the odontogenic keratocyst in vivo.

PMID- 11289628
TI  - Orbital myiasis: a case report.
AB  - Myiasis; a term first introduced by HOPE refers to invasion of living tissue of
      humans and other mammals by the eggs or larvae of flies of the order of Diptera.
      Orbital involvement occurs in approximately 5% of all cases of myiasis. A 72 year
      old patient is presented with orbital myiasis that was successfully treated by
      enucleation and grafted with split thickness of skin.

PMID- 11289629
TI  - Cervical spine injury in the elderly: imaging features.
AB  - An increase in the elderly population has resulted in an increased incidence of
      cervical spine injury in this group. No specific type of cervical spine trauma is
      seen in the elderly, although dens fractures are reported to be common.
      Hyperextension injuries due to falling and the resultant central cord syndrome in
      the mid and lower cervical segments due to decreased elasticity as a result of
      spondylosis may be also characteristic. The imaging features of cervical spine
      injury are often modified by associated spondylosis deformans, DISH and other
      systemic disorders. The value of MR imaging in such cases is emphasized.

PMID- 11289630
TI  - MR imaging of the wrist in rheumatoid arthritis using gadobenate dimeglumine.
AB  - OBJECTIVE: To determine the dosage of gadobenate dimeglumine (Gd-BOPTA) necessary
      for MRI of rheumatoid arthritis of the wrist. DESIGN AND PATIENTS: Seven wrists
      inflamed with rheumatoid arthritis were imaged using a dedicated 0.2-T MR unit.
      Four cumulative dosages of 0.0125, 0.025, 0.05 and 0.1 mmol/kg body weight (BW)
      Gd-BOPTA were tested. Three-dimensional T1-weighted gradient-recalled echo
      sequences (GRE; TR: 100 ms, TE: 18 ms, flip angle 90 degrees , 4:55 min) were
      acquired prior to an intravenous injection and after each additional dosage of Gd
      BOPTA. Relative enhancement, signal-difference-to-noise ratios (SDNRs) and the
      size of the inflamed tissue were quantified. Three radiologists independently
      evaluated the image quality, the size and the contrast of the enhancing tissue.
      RESULTS: The readers agreed on a dose of 0.05 mmol/kg BW as satisfactory for the
      evaluation of the size of the inflammatory tissue and for determination of bone
      involvement (kappa = 0.9, P < 0.001). Highly inflammatory pannus was depicted
      with adequate image contrast using 0.025 mmol/kg BW Gd-BOPTA. According to the
      SDNR and relative enhancement findings, a dose of 0.05 mmol/kg BW suffices for
      both off-center and centered regions of tissue inflammation (t-test, P < 0.05).
      CONCLUSION: Gadolinium-BOPTA is an alternative contrast agent for MRI of
      rheumatoid disease. This study shows that a dose of 0.05 mmol/kg BW suffices at
      low field strength.

PMID- 11289631
TI  - Synovial sarcoma: dynamic contrast-enhanced MR imaging features.
AB  - OBJECTIVE: To determine whether previously described so-called malignant dynamic
      contrast-enhanced magnetic resonance (MR) imaging features--early start,
      peripheral enhancement and early plateau or washout phase--occur consistently in
      synovial sarcoma. DESIGN AND PATIENTS: Dynamic contrast-enhanced MR images of 10
      patients with histologically proven synovial sarcoma were reviewed. The start,
      pattern and progression of tumor enhancement were assessed and correlated with
      histopathology. RESULTS: In all patients, the time interval between arterial and
      early tumor enhancement was less than 7 s (mean 4.40 s, SD 2.09 s). Six synovial
      sarcomas showed enhancement with a subsequent rapidly progressive linear increase
      in signal intensity followed by a plateau in one lesion and washout in five. Four
      lesions showed a late sustained increase in enhancement after the initial rapid
      increase in enhancement. The pattern of initial enhancement was peripheral in
      only two lesions, diffuse in four and heterogeneous in four lesions. CONCLUSIONS:
      Enhancement of tumor within 7 s after arterial enhancement is, of the three
      parameters described previously, the only sign that occurs consistently in
      synovial sarcoma.

PMID- 11289632
TI  - Radiographic diagnosis of rotator cuff tear based on the supraspinatus muscle
      radiodensity.
AB  - OBJECTIVE: To evaluate the supraspinatus muscle radiodensity on the outlet view
      as an indication of a tendon tear. DESIGN AND PATIENTS: Plain radiographs and
      magnetic resonance imaging (MRI) examinations were obtained on both shoulders of
      40 subjects aged 23-70 years, including 13 asymptomatic volunteers and 27
      patients. Two readers analyzed the superior contour and the heterogeneity of the
      supraspinatus muscle radiodensity and compared them with the MRI findings.
      RESULTS AND CONCLUSION: Significant concordances (P < 0.001) were found between
      the assessments of the superior contour and the heterogeneity of the muscle
      radiodensity, respectively, on plain radiographs and MR images. For the diagnosis
      of a full-thickness tear, the analysis of the superior contour and the
      heterogeneity of the muscle radiodensity reached an accuracy of 85% and 80%
      respectively. Stepwise discriminant analyses showed low to moderate benefit of
      considering the contour and the heterogeneity simultaneously. The inter- and
      intraobserver agreement ranged from moderate to good. We conclude that on the
      outlet view, modifications in the superior contour and heterogeneity of the
      supraspinatus muscle radiodensity suggest a full-thickness tear.

PMID- 11289633
TI  - Extraskeletal osteosarcoma arising in myositis ossificans.
AB  - A 53-year-old woman had extraskeletal osteosarcoma that developed from a soft
      tissue bony mass present on the volar aspect of the left wrist for 4 years.
      Initially, the bony mass was soft and movable, but during the first year it
      became hard and fixed. The patient had no history of trauma. Because the lesion
      did not grow or cause any symptoms, the patient did not come to the hospital
      until 4 years after she first noticed the lesion. Radiologically, the bony mass
      had features characteristic of mature myositis ossificans, showing "eggshell"
      ossification. A nonmineralized soft tissue mass occurred between the surface of
      the radius and the bony shell. Histologically, a high-grade osteosarcoma was
      present between the surface of the radius and the well-differentiated bone
      tissue, which included fatty and hematopoietic marrow. All the findings indicated
      that our patient had an extremely rare case of malignant transformation of
      myositis ossificans.

PMID- 11289634
TI  - Fibrosarcoma in bizarre parosteal osteochondromatous proliferation.
AB  - Bizarre parosteal osteochondromatous proliferation (BPOP) is a rare benign lesion
      predominantly involving the small bones of the hands and feet. Malignant
      transformation in BPOP has not been documented in the English literature. This
      report presents the coexistence of fibrosarcoma with BPOP in the right distal
      fibula of an 18-year-old woman.

PMID- 11289635
TI  - Progressive melorheostosis in the peripheral and axial skeleton with associated
      vascular malformations: imaging findings over three decades.
AB  - A 28-year old woman presented with Leri's disease (melorheostosis) and the rare
      combination of complex vascular malformations and lymphatic anomalies. Multifocal
      melorheostosis was segmental and unilateral, located in the left axial and
      peripheral skeleton, fifth thoracic vertebral body, fifth rib. left upper limb
      and lumbosacral spine (third lumbar body to first sacral segment). Sacral
      involvement was associated with spinal canal stenosis. Additionally the patient
      had multiple nevi and had suffered from left hemiplegia since birth.
      Lymphangiectasia of the mesentery and thorax led to chylothorax resistant to
      therapy for which the patient underwent a pleuropericardiectomy. Death ensued due
      to respiratory failure.

PMID- 11289636
TI  - Spontaneous osteonecrosis of the knee associated with ipsilateral tibial plateau
      stress fracture: report of two patients and review of the literature.
AB  - Two cases are presented of spontaneous osteonecrosis of the knee (SONK)
      associated with stress fractures of the tibial plateau. This association lends
      further credence to the postulate that SONK has a traumatic etiology.

PMID- 11289637
TI  - Unusual facet cyst containing struvite and hydroxyapatite.
AB  - This case report describes a patient with severe back pain and radiculopathy. She
      was found to have a facet cyst within the lumbar spine that appeared to contain
      calcium on MRI and CT. Upon aspiration the cyst was found to contain calcium
      ammonium phosphate (struvite) and calcium phosphate (hydroxyapatite). Ammonia
      production in the presence of urease-producing bacteria is responsible for the
      production of struvite in the human body. We postulate that there was a prior
      infection of the facet with urease-producing bacteria, thus accounting for the
      production of the struvite within the facet cyst.

PMID- 11289638
TI  - MRI of anterior cruciate ligament repair with patellar and hamstring tendon
      autografts.
AB  - OBJECTIVE: Several MRI sequences were used to evaluate the 2-year postoperative
      appearance of asymptomatic knee with a torn anterior cruciate ligament (ACL)
      reconstructed with bone-patellar tendon-bone (BTB) and semitendinosus and
      gracilis (STG) tendon autografts. DESIGN AND PATIENTS: Two groups with successful
      repair of ACL tear with BTB (n = 10) or STG (n = 10) autografts were imaged at
      1.5 T with sagittal and oblique coronal proton density-, T2-weighted and sagittal
      STIR sequences and plain and contrast-enhanced oblique coronal T1-weighted
      sequences. The appearance of the graft and periligamentous tissues was evaluated.
      RESULTS: In all 20 cases, the ACL graft showed homogeneous, low signal intensity
      with periligamentous streaks of intermediate signal intensity on T2-weighted
      images. In 10 cases, localised areas of intermediate signal intensity were seen
      in the intra-articular segment of the graft on proton density- and T1-weighted
      images. The graft itself did not show enhancement in either of the two groups,
      but mild to moderate periligamentous enhancement was detected in 10 cases.
      CONCLUSION: The MRI appearance of ACL autograft is variable on proton density-
      and T -weighted images. Periligamentous tissue showing contrast enhancement is a
      typical MRI finding after clinically successful ACL reconstruction.

PMID- 11289639
TI  - Health care legislative reforms in Armenia: preparations for a purchaser-provider
      split.
AB  - Armenia, the former Soviet republic, is switching its economy to a more market
      driven system. Where health care is concerned, the previous government planned to
      introduce an independent State Health Agency managing the available funds. At the
      same time, this Agency would be authorised to contract with former state
      hospitals and individual providers. The underlying idea was a partial withdrawal
      by the state from both the provision and financing of health care. However, since
      the financing system continued to be based on general taxation, the state's role
      has remained largely unchanged in this respect. This situation has created new
      difficulties. To solve the variety of emerging problems, the Armenian government
      requested technical support from the World Bank. As a member of a multi
      disciplinary team, the author will describe some major legal aspects of the
      underlying health policy reform plan and will conclude that the Agency's
      establishment will give an important impetus to the Armenian health care
      legislative reform process.

PMID- 11289640
TI  - The doctrine of two schools of thought--a shield or a sword.
AB  - This paper recognizes that, in medicine at least, there are at least two ways of
      looking at a problem, be it clinical or legal. The subject is approached from
      both viewpoints. Emphasis is placed on the background of legal concepts and their
      application to clinical situations. To illustrate the doctrine, the authors have
      drawn extensively on case law arising mainly in Israel, but also in the USA and
      Europe.

PMID- 11289641
TI  - Biotechnology-based foods: is there a third way between the precaution principle
      and an overly enthusiastic dissemination of GMO?
AB  - The demand for consumer safety with regard to the food-processing industry is
      becoming, legitimately, more and more urgent. If ingested drugs can carry
      deleterious effects that exceed the beneficial effect that the research was
      initially undertaken for, then the same can only be the case for foods that stem
      from the same new biotechnologies, zero risk being non existent.

PMID- 11289642
TI  - Patients' violence towards the staff in psychiatric institutions--a professional
      and ethical dilemma.
AB  - To address the violence phenomenon in psychiatric institutions towards the staff,
      to find the causes of these phenomena and to examine effective methods that will
      help to prevent the occurrence and/or confront it. To break the "conspiracy of
      silence" around the subject matter and to raise the awareness of all personnel in
      order to formulate a policy of responses to violent incidents and to learn
      procedures for the management of these complex situations.

PMID- 11289643
TI  - What the courts need to know about mental health diagnoses of abused women.
AB  - Abused women may appear before the courts because of family or criminal matters.
      It is not uncommon for an abused woman to be diagnosed as having a mental health
      condition, including a mental disorder. In this paper, we consider the
      implications of the use of mental health diagnoses in the court system. We
      discuss the diagnostic criteria in the DSM-IV and ICD-10 classification systems
      and examine what other information is needed by the courts to interpret the
      behaviour and thought processes of abused women. This other information includes:
      whether the abuse is continuing and the likely impact of its continuance,
      diagnosis and prognosis, as well as the woman's survival strategies, her coping
      mechanisms, her support systems, and the severity of the physical and/or
      psychological abuse. This information needs to be stated within the context of
      what we currently know about abuse, including up-to-date knowledge about its
      epidemiology (e.g., prevalence, physical and psychological manifestations, and
      complex psychological responses). Information about other intervening factors is
      essential for the courts; and in order to present meaningful testimony on these
      factors, it is critical for clinicians to have a thorough understanding of the
      complex dynamics of spousal abuse.

PMID- 11289644
TI  - The classification of epileptic seizures and syndromes.

PMID- 11289645
TI  - Epilepsy syndromes: effects on cognition, performance and driving ability.

PMID- 11289646
TI  - Courting disaster? A survey of the autopsy service provided by district surgeons
      in Kwazulu-Natal.
AB  - AIM: To provide information on the overall quality of the autopsy service
      provided by district surgeons in KwaZulu-Natal (KZN) and in particular to
      identify factors which may have a negative impact on the judicial process.
      METHOD: Confidential questionnaires were sent to 73 district surgeons and 216
      legal practitioners including prosecution advocates, regional court prosecutors,
      defence advocates and attorneys. One hundred and twenty (43%) replies (47 doctors
      and 73 lawyers) were suitable for analysis. RESULTS: District surgeons have no
      shortage of experience or maturity but their performance is hampered by the
      following: lack of appropriate training in forensic pathology; high case load;
      inadequate facilities and support staff; and lack of access to ancillary
      services. CONCLUSION: This study has shown that the standard of autopsy services
      by district surgeons varies considerably. Overall, there is evidence that
      inadequacies on the part of district surgeons have negative repercussions for the
      criminal justice system. Urgent attention should be given to implement training
      programmes for the district surgeons and to improve service conditions.

PMID- 11289647
TI  - Sexual assault and legal resolution: querying the medical collection of forensic
      evidence.
AB  - Very little is known about the role of medical evidence in the legal resolution
      of sexual assault cases. A retrospective review of hospital and police records
      was conducted to determine whether medico-legal evidence was related to the
      police laying of charges. Data were obtained from 187 female sexual assault
      victims who presented to a large urban hospital-based sexual assault treatment
      center and the police in Ontario, Canada between January 1 and December 31, 1994.
      Using stepwise logistic regression medico-legal variables were tested while
      controlling for non-medical factors. Neither the collection of sperm, semen
      and/or saliva nor the documentation of clinically observed injuries was
      significant in predicting an arrest and charge. In contrast, non-medical
      variables such as the victim's age, use of alcohol, resistance and relationship
      to the assailant, and the corroborating evidence of a witness were related to
      charge-laying. We question the value of uncritically continuing to collect
      medical forensic evidence.

PMID- 11289649
TI  - Allegations of sexual abuse in child custody disputes.
AB  - OBJECTIVE: Allegations of sexual abuse are increasingly made in the context of
      divorce proceedings. The aim of the study was to describe ideal typical patterns
      of family dynamics when sexual abuse is alleged in divorce proceedings. METHOD:
      Development of an assessment plan according to the methods of the qualitative
      descriptive social sciences and retrospective assessment of 24 legal cases of
      custody and visitation right proceedings in which allegations of sexual abuse (N
      = 30 children) were made. RESULTS: In our sample, we found a significant
      incidence of sexual deviations of a parent. With respect to the allegations of
      sexual abuse in divorce cases, we were able to identify four types of family
      dynamics. Our qualitative assessment of the data showed that distinguishing
      between actual abuse and false allegations cannot adequately help to clarify the
      family dynamics. Rather, it tends to conceal the fact that even a false
      allegation usually originates from a sexualized atmosphere in the family. The
      main family structures which were observed without exception in our sample
      generally already existed before the separation phase and had corresponding
      effects on the child which must be considered in the evaluation.

PMID- 11289648
TI  - Understanding oncology nurses' difficulties caring for suicidal people.
AB  - Clinical challenges occur when patients consider suicide. Despite improved
      treatment, people with cancer have an increased risk of suicide. While previous
      research examined patients' perspectives, this study describes the nurse's
      perspective of difficulty of caring for suicidal patients. Suicidal ideas
      constitute common psychiatric complications of cancer, however we know little of
      the nurse's difficulties in care giving. As part of a larger study of oncology
      nurses' knowledge, we randomly surveyed 1,200 clinical oncology nurses and 434
      returned completed questionnaires (37%). This paper describes content analysis of
      oncology nurses' narratives about their difficulties responding to suicidal
      patients. Six categories emerged: religious/other values, uncomfortable feelings,
      inadequate knowledge, personal experiences, and weight of professional
      responsibility which made it difficult for most nurses to care for suicidal
      patients. Some nurses reported they had no difficulties. Care giving is also
      difficult because the patient's right to choose suicide may conflict with the
      nurse's professional obligation to prevent suicide.

PMID- 11289650
TI  - Sex reassignment surgery in France: analysis of the legal framework and current
      procedures and its consequences for transsexuals.
AB  - MAIN OBJECTIVES: In France there is no specific law that recognizes either sex
      reassignment surgery (SRS) or changes in civil status. This practice is based on
      a set of rules that have been devised by those practitioners in the disciplines
      involved. This study has been directed to evaluate the perceptions of French
      surgeons regarding their own activity in the area of the SRS with the
      implications that these perceptions may have on the management of patients and to
      contribute to a useful international collection of material on this difficult
      topic in terms both of report and interpretation. METHODS: Personal interviews
      with 10 surgeons representing almost all of teams involved in transsexualism in
      France. The data were collected during 1998. FINDINGS: Surgeons alone cannot
      evaluate the motivation of each patient's request. Their decision whether or not
      to operate is made in consultation with both a psychiatrist and an
      endocrinologist. They never urge patients to undergo SRS. An assessment lasting
      at least two years before making a recommendation for surgery is routine. The
      rate of postoperative suicides is very low. Among surgeons, postoperative regrets
      are minimal (postoperative regrets by patients were not directly evaluated in the
      framework of this study). The diagnosis seems to be made with satisfactory
      reliability, but at the cost of a tedious process for the patient. As a
      consequence some decide to be operated on abroad. However not all are true
      transsexuals. CONCLUSION: SRS represents a good example of the collaboration of
      certain disciplines as surgery, medicine, psychiatry and law to reaffirm the
      meaning that society gives to the status of the individual while protecting the
      respect of some unusual situations.

PMID- 11289651
TI  - State regulation of donor insemination: an Israeli case study.
AB  - Donor insemination (DI) in Israel is state regulated. The Ministry of Health
      dictates a policy of total medicalization and secrecy. In this paper we analyze
      the state regulations in reference to their historical and cultural contexts. Our
      main argument is that in Israel, having children and establishing a family are of
      supreme importance, owing to Biblical myths as well as the Zionist ethos. The
      state, as the provider of health care services, encourages fertility treatments
      in general. However, DI, while assisting conception, results in a somewhat non
      traditional family. In contradiction to trends towards openness observed in
      Western countries, Israel's state policy is one of hiding and camouflaging. We
      attribute this policy to the strict support of the 'natural family' paradigm,
      which equally gives DI-assisted families a problem no less than a solution.

PMID- 11289652
TI  - Personal mastery in ethical leadership.
AB  - The paper briefly explores the manifestation of ethical leadership and examines
      at length the dimension of character formation. It argues that personal mastery
      is indispensable to sound character formation because leaders with high personal
      mastery are more likely to exhibit a disciplined pattern of behavior that is
      guided by a deep personal vision and enduring moral principles. The paper then
      discusses some of the sources that the leader can tap to attain personal mastery
      that leads to the self-transformation of both the leader and of the followers.

PMID- 11289653
TI  - Protective effects upon experimental inflammation models of a polyphenol
      supplemented virgin olive oil diet.
AB  - OBJECTIVE AND DESIGN: The aim of the present study was to examine the effect of a
      virgin olive oil enriched diet in acute and chronic inflammation models in rats
      and to determine the effect of supplementing this oil with a higher content of
      its polyphenolic fraction. The response was compared to oils rich in
      monounsaturated fatty acids (high oleic sunflower oil and palm olein) and rich in
      polyunsaturated fatty acids (fish oil). DIETS: Groups of 6-8 male Wistar rats
      were fed from weaning on six purified diets differing in type of oil: 2% corn oil
      (basal diet, BD), 15% high oleic sunflower oil (HOSO), 15% virgin olive oil
      (VOO), 15% virgin olive oil supplemented with 600 p.p.m. polyphenols from this
      oil (PSVOO), 15% palm olein (POL), and 15% fish oil (FO). MATERIALS AND METHODS:
      Rats were fed for 8 weeks with BD, HOSO, VOO, PSVOO, POL and FO diets before
      injecting carrageenan. Rats were fed for 3 weeks with BD, PSVOO and FO diets
      before induction of adjuvant arthritis. Dietary treatment with or without
      indomethacin continued during 3 weeks. The data were evaluated using an analysis
      of variance (ANOVA) followed by the least-significant differences. RESULTS: In
      carrageenan oedema test, the inflammation indices of animals fed on a diet rich
      in olive oil (VOO) were lower compared to animals fed with oils high in oleic
      acid (HOSO, POL) and polyunsaturated fatty acids (FO), and markedly diminished in
      the group fed on PSVOO. In established adjuvant arthritis, the PSVOO diet was
      even more effective than FO diet in the prevention of inflammation. Both groups
      of animals showed an increase in weight during the latter days of the experiment
      compared to the BD. Indomethacin administered to every diet group, exerted a
      strong inhibitory effect on the inflammatory process throughout which was
      augmented by the PSVOO and FO diets. CONCLUSIONS: This study demonstrates that
      virgin olive oil with a higher content of polyphenolic compounds, similar to that
      of extra virgin olive oil, shows protective effects in both models of
      inflammation and improves the disease associated loss of weight. This
      supplementation also augmented the effects of drug therapy.

PMID- 11289654
TI  - Accumulation of the neutrophil-derived protein YKL-40 during storage of various
      blood components.
AB  - OBJECTIVE AND DESIGN: Post transfusion infectious complications associated with
      allogeneic blood components may depend on storage time and may be related to
      extracellular accumulation of bioactive substances during storage. YKL-40 is a
      glycoprotein located in the specific granules of the neutrophils. While
      exocytosed it may play a role in inflammation and remodelling of the
      extracellular matrix. We studied the potential accumulation of YKL-40 in blood
      components during storage. METHODS: Using a RIA method extracellular accumulation
      of YKL-40 was determined in supernatants from whole blood, plasma-reduced whole
      blood, buffy-coat-depleted SAGM (saline-adenine-glucose-mannitol) blood, whole
      blood leukocyte depleted by prestorage filtration, and whole blood leukocyte
      depleted by bedside filtration. The blood was donated by volunteer, healthy blood
      donors, and stored under standard blood bank conditions for 35 days. RESULTS:
      Extracellular accumulation of YKL-40 increased significantly in a time-dependent
      manner during storage for 35 days of non-filtered whole blood, plasma-reduced
      whole blood, and SAGM blood, respectively. Prestorage leukocyte depletion of
      whole blood prevented extracellular YKL-40 accumulation, while YKL-40
      accumulation was not reduced by bedside leukocyte depletion. CONCLUSION: YKL-40
      appears to accumulate extracellularly in a time-dependent manner in standard
      erythrocyte components. Prestorage leukocyte depletion by filtration of whole
      blood may be an effective procedure to prevent extracellular YKL-40 accumulation
      during storage of erythrocyte components.

PMID- 11289655
TI  - Radiopharmaceuticals for scintigraphic imaging of infection and inflammation.
AB  - Scintigraphic imaging of infection and inflammation is a powerful diagnostic tool
      in the management of patients with infectious or inflammatory diseases. Most
      infectious and inflammatory foci can be visualized accurately with radiolabeled
      autologous leukocytes. However, preparation of this radiopharmaceutical is
      laborious and requires the handling of potentially contaminated blood. Nowadays,
      a few radiopharmaceuticals are available that could replace radiolabeled
      leukocytes, such as: 67Ga-citrate, 99mTc-IgG and 99mTc-labeled antigranulocyte
      antibody preparations. Furthermore, various agents labeled with 99mTc are
      currently developed for this application: chemotactic peptides, cytokines and
      liposomes. Here, the characteristics and the diagnostic potential of established
      and experimental radiopharmaceuticals for infection and inflammation imaging are
      reviewed.

PMID- 11289656
TI  - An investigation of cell proliferation and soluble mediators induced by
      interleukin 1beta in human synovial fibroblasts: comparative response in
      osteoarthritis and rheumatoid arthritis.
AB  - OBJECTIVES AND DESIGN: The difference in cell proliferation and release of
      soluble factors in response to interleukin 1beta (IL-1beta) in fibroblasts
      obtained from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) and
      from normal skin has been investigated. TREATMENT: The cells were treated with
      recombinant IL-1beta in the presence or absence of pharmacological agents for 24
      h or 48 h. METHODS: Cell proliferation was examined by WST-1 assay, and the
      amounts of interleukin-6 (IL-6), interleukin-8 (IL-8), macrophage colony
      stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix
      metalloproteinase-1 (MMP-1), and prostaglandin E2 (PGE2) were measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: IL-1beta dose-dependently enhanced
      the proliferation of all fibroblasts. The proliferative response to IL-1beta in
      RA synovial fibroblasts was greater than that in OA synovial and skin
      fibroblasts. However, there was no difference in spontaneous levels of soluble
      factors between OA and RA fibroblasts, though medium concentrations of IL-1beta
      released VEGF, MMP-1, and PGE2, but not cytokines, in RA were slightly higher
      than those in OA. Ability to release soluble mediators was pronouncedly increased
      at 3 h to 9 h after stimulating fibroblasts with IL-1beta for 1 h. The
      proliferative response to IL-1beta in all fibroblasts was inhibited by
      dexamethasone and the NF-kappaB inhibitor hymenialdisine but not the
      cyclooxygenase 2 (COX-2) inhibitor NS-398. But PGE2 prevented proliferation of RA
      fibroblasts when added to medium up to 3 h after IL-1beta stimulation.
      Dexamethasone also inhibited the release of IL-6, IL-8, and PGE2 induced by IL
      1beta in both OA and RA fibroblasts. NS-398 exhibited an inhibition of IL-1beta
      induced IL-6 production as well as PGE2 production. Hymenialdisine inhibited IL-6
      production and reduced IL-8 production dependent on synovial cell strains.
      Methotrexate had no effect on the response to IL-1beta in synovial fibroblasts.
      CONCLUSION: The present results indicate that the activation of NF-kappaB plays
      an important role in the proliferative response to IL-1beta in human fibroblasts,
      and suggest that PGE2 acts as a modulator of cell proliferation in inflamed
      synovial tissue. It appears that the ability to produce soluble factors in RA
      synovial fibroblasts is not intrinsic. However, the response to IL-1beta in RA
      cells seems to be greater than that in OA cells.

PMID- 11289657
TI  - Regulation of cell proliferation, inflammatory cytokine production and calcium
      mobilization in primary human T lymphocytes by emodin from Polygonum hypoleucum
      Ohwi.
AB  - OBJECTIVE AND DESIGN: This study was designed to elucidate action mechanisms of
      four anthraquinones identified from Polygonum hypoleucum Ohwi (P. hypoleucum
      Ohwi) on primary human T lymphocytes. MATERIAL AND METHODS: The cells were
      isolated from peripheral blood. TREATMENT: T cells were treated with 5 to 60
      microM of four anthraquinones with or without phytohemagglutinin (PHA; 5
      microg/ml) for 3 days. Effects of 4 anthraquinones on T lymphocyte proliferation,
      production and gene expression of inflammatory cytokines and intracellular free
      Ca2+ concentration ([Ca2+]i) were determined. Data were assessed with Student's t
      test. RESULTS: On a percentage basis, emodin had the highest suppressing activity
      on T lymphocyte proliferation with an IC50 of 11.2 +/- 0.6 microM. Emodin
      decreased cytokine production, IL-2 mRNA expression, and [Ca2+]i in activated T
      cells. CONCLUSIONS: We hypothesize that the inhibitory mechanisms of emodin on
      activated T cells proliferation are related to the impairment of cytokine
      production, IL-2 mRNA level and [Ca2+]i in the cells.

PMID- 11289658
TI  - Role of nitric oxide in zymosan induced paw inflammation and thermal
      hyperalgesia.
AB  - OBJECTIVE: To assess the involvement of spinal inducible nitric oxide synthase
      (iNOS) in inflammation and nociception. MATERIALS AND METHODS: The time course of
      iNOS mRNA expression in rat spinal cord and inflamed paw was assessed by means of
      quantitative real time RT-PCR. In addition, the effects of the iNOS inhibitor L
      NIL on inflammatory paw edema and thermal hyperalgesia were studied in comparison
      to those of the NO-donor RE-2047. L-NIL (3, 9, 27 and 81 mg/kg) and RE-2047 (3, 9
      and 27 mg/kg) or vehicle were administered orally 15 min prior to the
      intraplantar injection of 0.625 mg zymosan. RESULTS: Following zymosan injection,
      mRNA expression of iNOS increased in the inflamed paw and spinal cord with a
      maximum at 2.5 and 4 h, respectively. In the spinal cord iNOS mRNA started to
      decline at 10 h whereas it remained at maximum in the inflamed paw up to the end
      of the observation period of 24 h. As expected, RE-2047 had significant
      pronociceptive and proinflammatory effects. L-NIL significantly reduced paw
      inflammation at 27 and 81 mg/kg but failed to reduce hyperalgesia at the doses
      tested. CONCLUSIONS: The results show that iNOS is upregulated in the inflamed
      tissue and spinal cord with a similar time course. The effects obtained with L
      NIL suggest that iNOS differently contributes to the inflammatory and nociceptive
      response induced by zymosan.

PMID- 11289659
TI  - S-nitrosoglutathione inhibits TNF-alpha-induced NFkappaB activation in
      neutrophils.
AB  - OBJECTIVE AND DESIGN: Cytokine expression is controlled by transcription factors
      including NFkappaB, which has recently been found to exist in human neutrophils.
      We previously showed that exogenous nitric oxide (NO) induces neutrophil
      apoptosis and hypothesized that this NO effect could be mediated by inhibition of
      NFkappaB activation. MATERIALS AND METHODS: Isolated human neutrophils were
      incubated with or without S-nitrosoglutathione (GSNO 0.1 mM-5 mM; Sigma) for 2 h.
      Neutrophils were either unstimulated or stimulated with TNFalphalpha or n-formyl
      methionyl leucine phenylalanine (fMLP). Viability was assessed by vital dye
      cytotoxicity assay. After nuclear extraction and measurement of protein
      concentration, NFkappaB binding was determined by electrophoretic mobility shift
      assay. Effects of GSNO on activation of IkappaB alpha, which inhibits
      intranuclear translocation of NFkappaB, were measured by Western immunoblot
      technique. For comparison, experiments were also performed in the presence of the
      NFkappaB inhibitor PDTC. RESULTS: TNFalpha increased nuclear NFkappaB activity
      compared to unstimulated neutrophils (p < 0.001, n = 5). GSNO (500 microM)
      decreased TNFalpha-induced NFkappaB activity (p<0.05) and inhibited NFkappaB
      activity whether given prior to or during TNFalpha exposure. IkappaB alpha was
      significantly degraded at 30 and 120 min of TNFalpha exposure compared to control
      neutrophils (p < 0.05). GSNO exposure (500 microM) inhibited IkappaB alpha
      degradation in the presence of TNFalpha. PDTC enhanced neutrophil cell death and
      DNA fragmentation, in association with decreased NFkappaB activity, similar to
      GSNO effects. CONCLUSION: Neutrophils possess NFkappaB activity that is increased
      by stimulation with TNFalpha. GSNO inhibits NFkappaB activity in association with
      inhibiting TNFalpha-induced degradation of IkappaB alpha. GSNO effects are
      similar to those seen with NFkappaB inhibition by PDTC. Inhibition of NF kappaB
      could represent a potential anti-inflammatory effect of GSNO.

PMID- 11289660
TI  - Inhibition of 5-lipoxygenase activity by the natural anti-inflammatory compound
      aethiopinone.
AB  - OBJECTIVE AND DESIGN: We have investigated the mechanisms of action of
      aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots.
      MATERIAL AND SUBJECTS: Human neutrophils from healthy volunteers and murine
      peritoneal macrophages. Swiss mice were randomly divided into groups of six
      animals. TREATMENT: Test compounds were applied topically in the mouse ear oedema
      test. In the air pouch, mice received aethiopinone (0.001-0.5 pmol/pouch or 12.5
      50 mg/kg p.o.). METHODS: LTB4 production was assayed in human neutrophils and COX
      2 and iNOS activities in murine macrophages. Air pouches were induced
      subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema
      was induced by arachidonic acid. Dunnett's t-test was employed for statistical
      analysis. RESULTS: We have observed potent inhibitory effects on human neutrophil
      LTB4 production without effects on COX or NOS activities. Aethiopinone is an in
      vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 microM). In addition,
      aethiopinone reduced leukocyte accumulation and showed in vivo inhibitory
      activity on this enzyme. CONCLUSIONS: Our results indicate that inhibition of 5
      LO could participate in the anti-inflammatory properties of this natural product.

PMID- 11289661
TI  - A simplified model for predicting malaria entomologic inoculation rates based on
      entomologic and parasitologic parameters relevant to control.
AB  - Malaria transmission intensity is modeled from the starting perspective of
      individual vector mosquitoes and is expressed directly as the entomologic
      inoculation rate (EIR). The potential of individual mosquitoes to transmit
      malaria during their lifetime is presented graphically as a function of their
      feeding cycle length and survival, human biting preferences, and the parasite
      sporogonic incubation period. The EIR is then calculated as the product of 1) the
      potential of individual vectors to transmit malaria during their lifetime, 2)
      vector emergence rate relative to human population size, and 3) the
      infectiousness of the human population to vectors. Thus, impacts on more than one
      of these parameters will amplify each other's effects. The EIRs transmitted by
      the dominant vector species at four malaria-endemic sites from Papua New Guinea,
      Tanzania, and Nigeria were predicted using field measurements of these
      characteristics together with human biting rate and human reservoir
      infectiousness. This model predicted EIRs (+/- SD) that are 1.13 +/- 0.37 (range
      = 0.84-1.59) times those measured in the field. For these four sites, mosquito
      emergence rate and lifetime transmission potential were more important
      determinants of the EIR than human reservoir infectiousness. This model and the
      input parameters from the four sites allow the potential impacts of various
      control measures on malaria transmission intensity to be tested under a range of
      endemic conditions. The model has potential applications for the development and
      implementation of transmission control measures and for public health education.

PMID- 11289663
TI  - Quantitative competitive PCR as a technique for exploring flea-Yersina pestis
      dynamics.
AB  - We used a quantitative competitive polymerase chain reaction assay to quantify
      Yersinia pestis loads in fleas and bacteremia levels in mice that were used as
      sources of infectious blood meals for feeding the fleas. Xenopsylla cheopis, the
      Oriental rat flea, achieved higher infection rates, developed greater bacterial
      loads, and became infectious more rapidly than Oropsylla montana, a ground
      squirrel flea. Both flea species required about 10(6) Y. pestis cells per flea to
      be able to transmit to mice. Most fleas that achieved these levels, however, were
      incapable of transmitting. Our results suggest that at the time of flea feeding,
      host blood must contain > or = 10(6) bacteria/ml to result in detectable Y.
      pestis infections in these fleas, and > or = 10(7) bacteria/mL to cause infection
      levels sufficient for both species to eventually become capable of transmitting
      Y. pestis to uninfected mice. Yersinia pestis colonies primarily developed in the
      midguts of O. montana, whereas infections in X. cheopis often developed
      simultaneously in the proventriculus and the midgut. These findings were visually
      confirmed by infecting fleas with a strain of Y. pestis that had been transformed
      with the green fluorescent protein gene.

PMID- 11289664
TI  - Mosquito isolates of Ross River virus from Cairns, Queensland, Australia.
AB  - During 1996-1998 60,619 mosquitoes were collected around Cairns, Australia and
      processed for Alphavirus isolation. Thirty-three isolates of Ross River (RR)
      virus were made from 9 species, Aedes imprimens, Aedes kochi, Aedes notoscriptus,
      Aedes vigilax, Culex annulirostris, Culex gelidus, Mansonia septempunctata,
      Verrallina (formerly Aedes) carmenti, and Verrallina lineatus. Attempts to
      isolate RR virus from 121 Aedes aegypti were unsuccessful. Twenty-six (79%) of
      the isolates came from within 1 km of a colony of spectacled flying-foxes,
      Pteropus conspicillatus. The minimum infection rate for these mosquitoes was 1.0
      compared with 0.2 per 1,000 for mosquitoes trapped at all other sites. Ross River
      virus has not previously been isolated from Ae. imprimens, Cx. gelidus, Ma.
      septempunctata, Ve. carmenti, or Ve. lineatus. This is also the first isolation
      of an arbovirus from Cx. gelidus in Australia. In conclusion, the vector status
      of Ve. carmenti, Ae. aegypti and Ma. septempunctata warrants further study. This
      study also provides evidence that P. conspicillatus may be a reservoir host.

PMID- 11289662
TI  - The potential impact of integrated malaria transmission control on entomologic
      inoculation rate in highly endemic areas.
AB  - We have used a relatively simple but accurate model for predicting the impact of
      integrated transmission control on the malaria entomologic inoculation rate (EIR)
      at four endemic sites from across sub-Saharan Africa and the southwest Pacific.
      The simulated campaign incorporated modestly effective vaccine coverage, bed net
      use, and larval control. The results indicate that such campaigns would reduce
      EIRs at all four sites by 30- to 50-fold. Even without the vaccine, 15- to 25
      fold reductions of EIR were predicted, implying that integrated control with a
      few modestly effective tools can meaningfully reduce malaria transmission in a
      range of endemic settings. The model accurately predicts the effects of bed nets
      and indoor spraying and demonstrates that they are the most effective tools
      available for reducing EIR. However, the impact of domestic adult vector control
      is amplified by measures for reducing the rate of emergence of vectors or the
      level of infectiousness of the human reservoir. We conclude that available tools,
      including currently neglected methods for larval control, can reduce malaria
      transmission intensity enough to alleviate mortality. Integrated control programs
      should be implemented to the fullest extent possible, even in areas of intense
      transmission, using simple models as decision-making tools. However, we also
      conclude that to eliminate malaria in many areas of intense transmission is
      beyond the scope of methods which developing nations can currently afford. New,
      cost-effective, practical tools are needed if malaria is ever to be eliminated
      from highly endemic areas.

PMID- 11289665
TI  - Antibody responses to Plasmodium falciparum: evolution according to the severity
      of a prior clinical episode and association with subsequent reinfection.
AB  - We measured sporozoite- and total parasite antigen-specific IgG and IgM
      antibodies before and after treatment in matched groups of Gabonese children who
      presented with either mild or severe Plasmodium falciparum malaria. We
      investigated the influence of various parameters on these antibody responses,
      including clinical presentation, age, and post-treatment reinfection profiles.
      IgG but not IgM responses were strongly influenced by both clinical and
      parasitological status. IgG responses to the repeat region of the
      circumsporozoite protein, which were low at admission, particularly so in those
      with severe anemia, increased after treatment but showed no association with
      either age or reinfection profiles. Total parasite antigen-specific IgG responses
      were strongly influenced by parasitological status, and also differed
      significantly when segregated according to clinical status at admission, age, and
      reinfection histories. Most notably, anti-parasite IgG responses measured when
      children were parasite-free were higher and a good indicator of recent
      reinfections in those who presented with mild rather than with severe malaria.
      The profile of responses in the latter group suggests some immune system
      dysfunction, which may reflect the induction of tolerance to parasite antigens.

PMID- 11289666
TI  - Assessment of the antimalarial potential of tetraoxane WR 148999.
AB  - The antimalarial peroxide, dispiro-1,2,4,5-tetraoxane WR 148999, was synergistic
      with chloroquine, quinine, mefloquine, and artemisinin against both D6 and W2
      clones of Plasmodium falciparum. In consideration of the contrasting antagonism
      between artemisinin and chloroquine, these drug combination data imply that WR
      148999 and artemisinin may not share a common mechanism of action. For Plasmodium
      berghei-infected mice given oral, subcutaneous, and intraperitoneal doses of WR
      148999 ranging from 2 to 1024 mg/kg in the Thompson test, median survival times
      were 8.8, 11.8, and 27.5 days, respectively, compared to 8 days for control
      animals. Using subcutaneous administration, WR 148999 had a considerably longer
      duration of action than did artemisinin against P. berghei. WR 148999 did not
      significantly inhibit cytochrome P450 isozymes CYP 2C9, 2C19, 2D6, 2E1, or 3A4
      (IC50 >500 microM) but did inhibit CYP 1A2 with an IC50 value of 36 microM,
      suggesting that WR 148999 may be metabolized by the latter CYP isozyme. These
      results combined with previous observations that formulation strategies and
      incorporation of polar functional groups in a series of WR 148999 analogs both
      failed to enhance tetraoxane oral antimalarial activity suggest that oral
      bioavailability of tetraoxane WR 148999 is more likely a function of extensive
      first-pass metabolism rather than solubility-limited dissolution.

PMID- 11289667
TI  - Comparison of antigen-capture ELISA to stool-culture methods for the detection of
      asymptomatic Entamoeba species infection in Kafer Daoud, Egypt.
AB  - We performed a prospective field study in the village of Kafer Daoud in Menofia,
      Egypt to compare the fecal culture method with enzyme linked immuno assay (ELISA)
      for detection of 170 kDa lectin antigen in feces for diagnosis of asymptomatic
      Entamoeba histolytica and Entamoeba dispar infection. All subjects with E.
      histolytica or E. dispar infection detected by culture also had positive ELISA
      for amebic antigen in their feces and an additional 57 Entameoba infections
      missed by culture were detected by ELISA (P < 0.001 compared to culture). The
      presence of fecal anti-lectin IgA antibodies and serum anti-LC3 (recombinant
      cysteine-rich lectin protein) IgG antibodies were positive predictors for E.
      histolytica infection (P < 0.03). Of interest, infection with Trichomonas hominis
      but not Blastocystis hominis was positively associated with E. histolytica
      infection (P < 0.05). In conclusion, ELISA for detection of fecal lectin antigen
      is a more sensitive method than fecal culture for detecting asymptomatic E.
      histolytica infection.

PMID- 11289668
TI  - Solitary subcutaneous hydatid cyst: a case report.
AB  - In the absence of hepatic and pulmonary involvement, hydatid disease of other
      organs is extremely rare. In this paper, we report on a patient who had a
      solitary subcutaneous hydatid cyst in the submandibular region.

PMID- 11289669
TI  - Occurrence and self-treatment of diarrhea in a large cohort of Americans
      traveling to developing countries.
AB  - There is little information available regarding traveler's diarrhea that affects
      a large number of Americans who differ widely in age and travel destination, and
      little or no information exists on self-treatment. This paper describes the
      clinical features, self-treatment, and outcome of diarrhea in 784 (95% follow-up)
      Americans who traveled for < or = 90 days, and who received detailed pre-travel
      advice. Diarrhea was reported by 46%. Of these, 34% (n = 270) had traveler's
      diarrhea (TD) defined as > or = 3 unformed stools/day +/- enteric symptoms or < 3
      stools/day with > or = 1 enteric symptom, and 11% (n = 88) had loose motions
      (LM). Diarrhea was often severe and nearly a quarter of people with TD
      experienced fever and vomiting and 35% were required to alter their plans. The
      duration of travel and the destination itself were the strongest influences on
      diarrhea. Most travelers treated the illness themselves, whether or not they had
      LM (72%) or TD (83%). Those with LM took an antimotility agent or bismuth
      subsalicylate alone more frequently than those with TD (71% versus 48%, P <
      0.002). Conversely, antibiotics were taken more frequently by those with TD (47%
      versus 27%, P < 0.03). Overall, 83% indicated self-treatment was effective (91%
      with LM and 80% with TD). Diarrhea is common despite pre-travel advice. Because
      travelers usually treat themselves, they should be provided with clear
      instructions on appropriate self-treatment.

PMID- 11289670
TI  - Vitamin A supplementation and other predictors of anemia among children from Dar
      Es Salaam, Tanzania.
AB  - The associations of hemoglobin, hematocrit, and packed cell volume with
      socioeconomic factors, malaria, human immunodeficiency virus (HIV) infection, and
      nutritional status were examined among 687 children admitted to hospital with
      pneumonia participating in a double blind, placebo-controlled trial of vitamin A
      supplementation. Children were randomized to receive 2 doses of vitamin A
      (200,000 IU) or placebo at baseline, and additional doses at 4 and 8 months after
      discharge from hospital. Hemoglobin levels were measured at enrollment and, on a
      subset of 161 children, during follow-up. At baseline, hemoglobin concentration
      was positively associated with the number of possessions in the household,
      maternal level of education and quality of water supply, and inversely related to
      malaria infection after controlling for potential confounding variables. Children
      infected with HIV experienced a significant fall in mean hemoglobin levels over
      time. The risk of developing severe anemia (< 7 g/dL) during follow-up was lower
      for children who were breastfed for longer than 18 months as compared to those
      with less than 6 months of breastfeeding (adjusted prevalence ratio = 0.14, 95%
      confidence interval [CI] = 0.02, 0.93; P = 0.04), and higher for children over
      two years of age as compared to 6 to 11 months-old infants (adjusted prevalence
      ratio = 8.11, 95% CI = 1.2, 55.8; P = 0.03). Children with repeated diagnoses of
      malaria had 4.1 times the risk of developing severe anemia than did children
      without the diagnosis (95% CI = 1.3, 13.5; P = 0.02). Vitamin A supplements were
      associated with an overall nonsignificant reduction of 14% in the risk of
      developing severe anemia (adjusted prevalence ratio = 0.86, 95% CI = 0.37, 1.99;
      P = 0.73). We conclude that malaria, HIV infection, low socioeconomic status, and
      short duration of breastfeeding are strong and independent determinants of
      adverse hematologic profiles in this population.

PMID- 11289671
TI  - Phylogenetic analysis of the rompB genes of Rickettsia felis and Rickettsia
      prowazekii European-human and North American flying-squirrel strains.
AB  - The rickettsial outer membrane protein B (rompB) gene encodes the major surface
      antigens of Rickettsia species. We undertook sequencing and molecular analysis of
      the rompB gene of Rickettsia felis and a comparison with its homologs in spotted
      fever group (SFG) and typhus group (TG) rickettsiae, including the complete
      sequences of two North American flying squirrel strains and two European human
      strains of Rickettsia prowazekii. We sequenced 5,226 base pairs (bp) of the R.
      felis rompB, encoding a protein of 1,654 amino acids. We also sequenced 5,015 bp
      of rompB of the flying squirrel strains, encoding a protein of 1,643 amino acids.
      Analysis of the R. felis rompB gene sequence showed 10-13% divergence from SFG
      rickettsiae and 18% divergence from the TG rickettsiae. The rompB of all
      sequenced strains of R. prowazekii showed an overall similarity of 99.7-99.9%.

PMID- 11289672
TI  - Infection with different Trypanosoma cruzi populations in rats: myocarditis,
      cardiac sympathetic denervation, and involvement of digestive organs.
AB  - We tested four isolates of Trypanosoma cruzi to assess parasite virulence and
      ability to cause myocarditis, cardiac sympathetic denervation, and
      histopathologic alterations in organs of the digestive system. The susceptibility
      of rats depends on the population of T. cruzi, with the ABC strain and the CL
      Brener clone killing all animals, regardless of the parasitemic pattern. All
      tested T. cruzi populations caused acute myocarditis, but failed to induce
      histologic alterations in the intestine. The Cl-Brener and ABC isolates caused
      esophageal myositis. The myocarditis caused by the ABC, CL-Brener, and Y isolates
      was severe, but resolution started at the end of the acute phase. In contrast,
      the Col 1.7 G2 clone induced mild and sustained myocarditis. Our results also
      showed that T. cruzi populations able to induce severe acute myocarditis caused
      marked sympathetic denervation, but recovery of normal cardiac histology and
      innervation occurred. The sustained myocarditis induced by Col 1.7 G2 clone
      failed to cause sustained denervation.

PMID- 11289673
TI  - Cost-effectiveness analysis of reacquiring and using adenovirus types 4 and 7
      vaccines in naval recruits.
AB  - Adenovirus vaccines have controlled acute respiratory disease (ARD) in military
      recruits since 1971. Vaccine production, however, ceased and new facilities are
      required. We assessed whether reacquiring and using vaccines in naval recruits is
      cost-effective. Three policy options were evaluated: no vaccination, seasonal
      vaccination, and year-round vaccination. Morbidity (outpatient and inpatient),
      illness costs (medical and lost training), and vaccine program costs (start-up,
      acquisition, and distribution) were modeled using a decision-analytic method.
      Results were based on a cohort of 49,079 annual trainees, a winter vaccine
      preventable ARD rate of 2.6 cases per 100 person-weeks, a summer incidence rate
      at 10% of the winter rate, a hospitalization rate of 7.6%, and a production
      facility costing US$12 million. Compared to no vaccination, seasonal vaccination
      prevented 4,015 cases and saved $2.8 million per year. Year-round vaccination
      prevented 4,555 cases and saved $2.6 million. Reacquiring and using adenovirus
      vaccines seasonally or year-round saves money and averts suffering.

PMID- 11289674
TI  - An outbreak of hepatitis E in Northern Namibia, 1983.
AB  - In 1983 in Namibia's Kavango region, epidemic jaundice affected hundreds of
      people living in settlements lacking potable water and waste disposal facilities.
      Many were Angolan refugees. The disease, which after investigation was designated
      non-A non-B hepatitis, was most common in males (72%), in persons aged 15-39
      years, and was usually mild except in pregnant women, who incurred 6 (86%) of the
      7 fatal infections. Fifteen years later, archived outbreak-associated samples
      were analyzed. Hepatitis E virus (HEV) was detected by reverse transcription
      polymerase chain reaction in feces from 9 of 16 patients tested. Total Ig and IgM
      to HEV were quantitated in serum from 24 residents of an affected settlement at
      the outbreak's end: 42% had IgM diagnostic of recent infection and 25% had
      elevated total Ig without IgM, consistent with past HEV infection. The Namibia
      outbreak was typical hepatitis E clinically and epidemiologically. This first
      report of hepatitis E confirmed by virus detection from southern Africa extends
      the known range of HEV and highlights its risk for refugees.

PMID- 11289675
TI  - Arenavirus antibody in rodents indigenous to coastal southern California.
AB  - The purpose of this study was to extend our knowledge on the geographic and
      natural rodent host ranges of New World arenaviruses in California. Sera from
      1,094 sigmodontine and 112 murine rodents were tested for antibody against
      Whitewater Arroyo and Amapari viruses. Antibody was found in 55 (4.6%) of the
      1,206 rodents: 4 from northwestern San Diego County, 3 from Los Angeles County,
      and 48 from Orange County. The antibody-positive rodents included 8 (7.8%) of 103
      Neotoma fuscipes, 1 (0.6%) of 180 Neotoma lepida, 1 (3.1%) of 32 Peromyscus
      boylii, 8 (11.0%) of 73 Peromyscus californicus, 1 (1.2%) of 85 Peromyscus
      eremicus, 30 (8.5%) of 353 Peromyscus maniculatus, and 6 (2.2%) of 268
      Reithrodontomys megalotis. This study provides the first evidence that New World
      arenaviruses occur in Los Angeles and Orange counties and northwestern San Diego
      County, and the first evidence that Peromyscus and Reithrodontomys species are
      naturally infected with New World arenaviruses.

PMID- 11289676
TI  - Isolation of Japanese encephalitis virus from mosquitoes (Diptera: Culicidae)
      collected in the Western Province of Papua New Guinea, 1997-1998.
AB  - After Japanese encephalitis (JE) virus emerged in the Torres Strait in Australia
      in 1995, investigations were initiated into the origin of the incursion. New
      Guinea was considered the most likely source, given its proximity to islands of
      the Torres Strait. Almost 400,000 adult mosquitoes were processed for virus
      isolation from 26 locations in the Western Province of Papua New Guinea (PNG)
      between February 1996 and February 1998, yielding three isolates of JE virus. Two
      isolates of Murray Valley encephalitis, 17 isolates of Sindbis, and 1 each of
      Sepik and Ross River viruses were also obtained. Nucleic acid sequences of the
      PNG JE isolates were determined in the prM region, and in a region overlapping a
      part of the fifth nonstructural protein and the 3' untranslated region. The PNG
      isolates belonged to genotype II, and shared > 99.2% identity with isolates from
      humans and mosquitoes from the Torres Strait, suggesting that PNG is the source
      of incursions of JE virus into Australia.

PMID- 11289677
TI  - Epidemiological and virological influenza survey in Dakar, Senegal: 1996-1998.
AB  - An influenza survey was conducted in seven sentinel sites in Dakar, Senegal from
      June 1996 to December 1998. Throat or nasal swab cultures were randomly collected
      from 804 patients suffering from influenza-like symptoms. Influenza viruses were
      isolated at a similar proportion in adults and in children (P = 0.29). Strains of
      influenza B viruses were isolated from sporadic cases in 1997, whereas type A
      virus was associated with an isolated peak. Proportions of influenza virus
      isolation varied from 17.5% to 40.0% between 1996 and 1998 during the peak period
      (July/September) of acute respiratory infection in Dakar. Rainfall, humidity, and
      temperatures rose during the same period. Influenza in Dakar seems to be an-all
      age groups respiratory infection characterized by high transmission during the
      hot and rainy season. The antigenic similarity of the A(H3N2) and B viruses to
      those circulating elsewhere in the world at the same time was confirmed. However,
      the A(H1N1) strains were found to be more closely related to an Asiatic strain
      which had not been isolated outside Asia previously. Consequently, the strain
      close to the A(H1N1)/Wuhan/371/95 strain isolated in Dakar was included in the
      composition of the 1998/1999 influenza vaccine. This reinforces the importance of
      setting up a national influenza control strategy in tropical regions.

PMID- 11289678
TI  - The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta region
      of Vietnam.
AB  - A population-based surveillance for typhoid fever was conducted in three rural
      communes of Dong Thap Province in southern Vietnam (population 28,329) for a 12
      month-period starting on December 4, 1995. Cases of typhoid fever were detected
      by obtaining blood for culture from residents with fever > or = 3 days. Among 658
      blood cultures, 56 (8.5%) were positive for Salmonella typhi with an overall
      incidence of 198 per 10(5) population per year. The peak occurrence was at the
      end of the dry season in March and April. The attack rate was highest among 5-9
      year-olds (531/10(5)/year), and lowest in > 30 year-olds (39/10(5)/year). The
      attack rate was 358/10(5)/year in 2-4 year-olds. The isolation of S. typhi from
      blood cultures was highest (17.4%) in patients with 5 to 6 days of fever. Typhoid
      fever is highly endemic in Vietnam and is a significant disease in both preschool
      and school-aged children.

PMID- 11289679
TI  - Simple anamnestic questions and recalled water-contact patterns for self
      diagnosis of Schistosoma mansoni infection among schoolchildren in western Cote
      d'Ivoire.
AB  - A study to determine the diagnostic performance of simple anamnestic questions
      and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni
      infection was carried out in western C te d'Ivoire. A total of 322 schoolchildren
      were screened over four consecutive days with the Kato-Katz technique to assess
      S. mansoni and concurrent geohelminth infections. Children were individually
      interviewed by teachers using a standardized questionnaire asking about symptoms,
      reported diseases, and water-contact patterns. The cumulative infection
      prevalence of S. mansoni was 76.4%. Univariate statistics revealed a significant
      association between the level of S. mansoni infection and three recalled water
      contact patterns: (1) fishing with nets, (2) swimming/bathing and (3) crossing
      rivers, but no significant association with reported symptoms and/or reported
      diseases. Multivariate analysis revealed significant adjusted odds ratios (OR)
      for crossing the river Tcheorbour (OR = 3.90, P = 0.007), crossing the river
      Sonbour (OR = 3.90, P = 0.008) and swimming/bathing in the latter (OR = 3.28, P =
      0.017). The diagnostic performance of these water-contact patterns was
      characterized by high specificities but low sensitivities, hence negative
      predictive values. In the village studied here, recalled water-contact patterns
      were more useful variables than anamnestic questions for schoolchildren's self
      diagnosis of S. mansoni infection, but no generalization of these findings beyond
      this population is possible at this time.

PMID- 11289680
TI  - Prevalence of Cryptosporidium parvum infection in children along the Texas-Mexico
      border and associated risk factors.
AB  - We examined the epidemiology of Cryptosporidium parvum in children aged 6 months
      to 13 years living in 1) colonias along the border (n = 105), 2) a clinic in an
      urban border community (n = 65), and 3) clinics in a large urban nonborder area
      (n = 109). Serum IgG and IgA anticryptosporidial antibodies were measured by
      enzyme-linked immunosorbent assay (ELISA). Overall, 70.2% (196/279) of subjects
      had detectable C. parvum antibodies. Prevalence rates were higher (93/105 [89%])
      in the colonias and urban border community (53/65 [82%]) compared to the urban
      nonborder community (50/109 [46%]). Within colonias, independent risk factors for
      C. parvum infection included consumption of municipal water instead of bottled
      water, older age, and lower household income. Children living along the Texas
      Mexico border have a higher rate of infection with C. parvum compared to children
      living in a large nonborder urban area. Within colonias, C. parvum infection was
      associated with source of water supply, age, and socioeconomic status.

PMID- 11289681
TI  - Self-reported musculoskeletal disorders among visiting and office home care
      workers.
AB  - This paper examines the associations between self-reported musculoskeletal
      disorders (MSDs) and work factors and injuries among home care workers. Based on
      99 focus group participants and 892 survey respondents, results show a high level
      of MSDs among both visiting and office home care workers. While visiting home
      care workers tend to feel pain in the back, office workers tend to report pain in
      the neck and shoulder. Hazards in clients' homes, injuries moving clients and
      stress are associated with self-reported MSDs for visiting home care workers.
      Repetitive tasks and stress are associated with self-reported MSDs for office
      home care workers. Age and months in the profession have no affect on self
      reported MSDs.

PMID- 11289682
TI  - Women's douching practices and related attitudes: findings from four focus
      groups.
AB  - PURPOSE: Vaginal douching is a common hygiene practice for many U.S. women, but
      is associated with several health risks. Little is known about the beliefs and
      attitudes that promote and maintain douching practices. This qualitative study,
      consisting of four focus groups of 31 southern women, was conducted to gather in
      depth information about attitudes and beliefs associated with douching. The focus
      groups consisted of separate groups of low-income and middle-income Caucasian and
      African-American women. RESULTS: The African-Americans and low-income Caucasians
      were more likely to douche than middle-income Caucasians. The participants
      reported douching after menstruation, after sexual intercourse, and at other
      times for cleanliness and odor control. Concern about odor and cleanliness was a
      recurrent theme, and douching was represented as an expected and necessary part
      of feminine hygiene. Several socioeconomic and racial differences were observed
      in douching practices and attitudes. CONCLUSIONS: This study provides preliminary
      information about women's douching practices and attitudes that may inform
      practitioners' educational efforts and future research.

PMID- 11289683
TI  - Reproductive health of homeless adolescent women in Seattle, Washington, USA.
AB  - OBJECTIVES: Homeless adolescent women are at high risk for negative health
      outcomes including early unplanned pregnancy and sexually transmitted diseases.
      The purpose of this study was to hear the perspectives of homeless adolescent
      females on the topics of health issues, self-care and fertility control, as well
      as on lessons from being homeless. DESIGN: The rescarch was descriptive, using
      semi-structured interviews and focus groups with a purposeful sample of 20 clinic
      based female youth ages 15-23 years. The data were coded and analyzed following
      standard qualitative tcchniques. RESULTS: The youth described female-specific
      health issues of being homeless, such as problems with hygiene, sexual
      exploitation, survival sex. Most knew of homeless female youth who had tried self
      induced abortions through drugs, herbs or physical abuse. They spoke of fertility
      control practices of young women living on the streets. The women also spoke of
      the lessons they had learned while being homeless, including the development of
      self-sufficiency. CONCLUSIONS: The young women in this study were willing to
      discuss their perspectives and experiences of being homeless. Health care
      providers should receive increased training in how to ask about sensitive
      subjects such as survival sex and the practice of self-induced abortions.
      Programs should be structured to ensure engagement of the women in healthy
      relationships with adults.

PMID- 11289684
TI  - Challenges of recruitment: focus groups with research study recruiters.
AB  - To rectify the historic lack of research on women's health and the exclusion of
      women from many significant clinical trials, regulations have been promulgated
      requiring the inclusion of women and minorities in research studies.
      Acknowledging that the National Institutes of Health (NIH) mandate has resulted
      in more inclusive research, the unintended consequences associated with
      implementation of these regulations must also be explored. While the requirements
      preclude the use of cost as a reason for excluding women and/or minorities, the
      additional funding necessary to recruit adequate numbers of study participants
      has not been provided. Consequently, study recruiters often face unacknowledged
      expectations and job pressures as they attempt to meet recruitment goals. While
      it is important to support the NIH mandate, the additional stress imposed upon
      research study recruiters must also be recognized. Focus groups with study
      recruiters from various backgrounds and types of research provide an
      understanding of the challenges recruiters face when attempting to recruit
      diverse populations of women into research, and provide an understanding of the
      impact of recruitment goals on study recruiters' job satisfaction.

PMID- 11289685
TI  - Singing "the baby blues": a content analysis of popular press articles about
      postpartum affective disturbances.
AB  - A content analysis was conducted to evaluate the description of postpartum mood
      disturbances in magazine articles that appeared during the years 1980-1998.
      Nineteen articles about postpartum depression and eight articles about "the baby
      blues" were identified and analyzed for their discussion of etiologies, symptoms,
      treatments, resources, and demographic assumptions about their readers. The
      results indicate a strong bias in favor of the medical model of postpartum
      affective disorders. The articles contained contradictory information about the
      definition, prevalence, onset, duration, symptoms, and treatment of postpartum
      disorders, and the authors generally assumed that their readers were
      heterosexual, married, and middle class. Although the purpose of the articles was
      to educate readers about an important topic in women's health, they failed to
      provide accurate information, and thus are not a sufficient resource for new
      mothers who are seeking to learn about psychosocial aspects of the postpartum
      period.

PMID- 11289686
TI  - Patient-blaming and representation of risk factors in breast cancer images.
AB  - Media coverage of some cancers in the past often equated cancer with a death
      sentence. Breast cancer coverage in 1990s magazines, however, has become less
      fatalistic, more frequent, and discusses a broader range of issues than before.
      This study examined whether the visual images accompanying magazine articles
      about breast cancer have also evolved. We used Goffman's (1976) rituals of
      subordination to measure patient-blaming and subordinating, disempowering images.
      We also analyzed race/ethnicity, body type, and age of females in the images to
      gauge whether these demographic risk factors were represented in a random sample
      of images from nine magazines over a 30-year period. Magazines analyzed
      represented three genres-women's magazines, fashion/beauty, and general news.
      Findings suggest that patient-blaming images have decreased in some categories
      and women portrayed are slightly more representative of risk factors of age and
      race/ethnicity. Magazine images tended to reinforce stereotyped portrayals of
      femininity to the detriment of cancer patients. Fashion/beauty magazines, aimed
      at younger women, were most likely to portray breast cancer images in
      stereotyped, patient-blaming ways, with the least representative images of risk
      factors. The social construction of feminine beauty seems to overpower accuracy
      in creating these images.

PMID- 11289687
TI  - Characteristics associated with recent recreational exercise among women 20 to 44
      years of age.
AB  - Data on 1,501 control women from a multi-center, population-based, case-control
      study of breast cancer were used to examine characteristics associated with
      recreational exercise during the year prior to the interview among women 20 to 44
      years of age. In a univariate analysis, higher levels of recreational exercise
      were associated with: higher education; higher family income; white race;
      previous participation in recreational exercise above the median level at ages 12
      to 13 and at age 20; being nulliparous; ever lactating; being a never or past
      smoker; having a low current Quetelet's index (QI: weight in kilograms divided by
      height in meters squared); and living in Atlanta or Seattle (compared to New
      Jersey). In a multiple linear regression model, independent predictors of higher
      levels of recreational exercise were: participation in higher levels of exercise
      at 20 years of age; having a low current QI; and never having smoked. Though all
      women should be encouraged to participate in exercise, these findings identity
      subgroups of women that may need targeting when developing exercise intervention
      programs.

PMID- 11289688
TI  - The mediating role of perceived control in the relationship between social ties
      and depressive symptoms.
AB  - This study first examines gender differences in the receipt and efficacy of four
      types of social ties. It is hypothesized that womens relationships involve more
      demanding social ties, which increase rather than decrease depressive symptoms.
      Next, this study explores the role of perceived control as a mediator in the
      relationship between social tics and depressive symptoms. It is hypothesized that
      the association between these social ties and depressive symptoms is mediated
      through perceived control. Results suggest that demanding social ties have the
      strongest association with depressive symptoms, and that this relationship is
      much stronger for women than for men. Emotional support is strongly associated
      with depressive symptoms for men and women, whereas instrumental support and
      number of close ties have negligible effects on depressive symptoms. Perceived
      control most strongly mediates (rather than moderates) those relationships with
      the strongest associations: demanding ties and depressive symptoms, and emotional
      support and depressive symptoms. Substantial direct associations between social
      ties and depressive symptoms remain after removing the effects mediated by
      perceived control.

PMID- 11289689
TI  - Higher osteocalcin levels and cross-links excretion in young men born with low
      birth weight.
AB  - As the result of accelerated growth, the final height of infants born with low
      birth weight (LBW) is near to the normal. Limited data are available about the
      bone density and bone turnover just after completion of skeletal development. We
      have investigated the bone turnover and bone density in 49 apparently healthy
      young LBW men (age 19-21 years; 21 born small for gestational age (SGA) and 28
      appropriate for gestational age (AGA)) and in 16 age-matched controls. Bone
      mineral density of lumbar spine, femoral neck, and radius midshaft, the markers
      of calcium homeostasis, biochemical parameters of bone turnover as serum
      osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD)
      levels were measured. Bone mineral densities of LBW subjects were not altered.
      Serum calcium (SGA: 2.44+/-0.15; AGA:2.41+/-0.17, control: 2.25+/-0.09
      mmol/liter, P < 0.05), OC (SGA:23.4+/-9.9; AGA:20.8+/-7.6; control:13.3+/-4.6
      ng/ml, P < 0.01), total alkaline phosphatase (AP) (SGA:201+/-61; AGA:193+/-81,
      control: 117+/-34 IU/liter, P < 0.01), and urinary DPD/creat (ln.values:
      SGA:3.10+/-0.48; AGA:3.17+/-0.46; control:2.58+/-0.57 nmol/mmol, P < 0.05) were
      higher, whereas fractional excretion of calcium (SGA:0.94+/-0.470; AGA: 1.03+/
      0.51, control:1.31+/-0.75%, P < 0.05) was lower in both SGA and AGA groups. PTH
      and 25OHD were not different. Significant correlation was obtained between seCa,
      OC, AP, DPD and birth weight of the subjects, but feCa correlated inversely to
      the birth weight. It was concluded that the bone turnover of LBW men is
      accelerated, but well balanced in young adulthood. Further investigation is
      needed to describe the possible link between accelerated bone turnover and
      hormonal homeostasis of LBW subjects.

PMID- 11289690
TI  - Absence of linkage for bone mineral density to chromosome 12q12-14 in the region
      of the vitamin D receptor gene.
AB  - Polymorphisms in the region of the gene for the vitamin D receptor (VDR)
      (chromosome 12q12-14) have been associated with differences in bone mineral
      density (BMD) in some studies but not in others. Because linkage analysis
      assesses allele sharing identical-by-descent among relatives instead of the
      association of a particular allele of an anonymous marker, we have performed a
      linkage study for bone BMD using microsatellite markers flanking the VDR locus.
      The present study explores whether or not relatives who share the chromosomal
      region containing the VDR gene have more similar bone density. Participants in
      the Framingham Osteoporosis Study (aged 37-89 years) who had undergone BMD
      testing were used to test for concordance of genotype with phenotype in the hip
      (femoral neck, Ward's area, trochanter) and lumbar spine (L2-L4) with adjustment
      for covariates. Multipoint quantitative trait linkage analysis using variance
      components methods was conducted with microsatellite markers flanking the VDR
      locus (GATA91H06, GATA5A09, GGAT2G06) in 332 extended families containing 1062
      individuals with both bone density measures and marker data. In addition,
      quantitative trait sib-pair linkage analysis, with a marker (AFM345xf1) in close
      proximity to the VDR locus, was performed in a second sample of 169 sibships (n =
      413), comprising 284 full-sib pairs. Neither analysis revealed evidence for
      linkage of this region to femoral neck, Ward's area, lumbar spine, and trochanter
      in age or sex BMI, and height-adjusted bone density measures. Additional
      adjustment for alcohol intake, caffeine consumption, smoking status, and estrogen
      supplement (female only) did not alter the results. The present study could not
      demonstrate linkage of BMD to chromosome 12q12-14. These findings suggest that
      neither the VDR gene nor other genes at this locus are likely to have a
      substantial impact upon bone density.

PMID- 11289691
TI  - Inhibition of bone resorption by divided-dose calcium supplementation in early
      postmenopausal women.
AB  - We have previously shown that a calcium (Ca) supplement of 1000 mg given in the
      evening reduces the overnight and early morning, but not the daytime, excretion
      of bone resorption markers in postmenopausal women within five years of the
      menopause. In the present study, we have looked at the effect of splitting the Ca
      into two doses of 500 mg each given in the morning and evening. We studied 19
      healthy women (median age 53 years) who were all within 5 years of the menopause.
      On the 2 study days, urine was collected from 9 a.m. to 9 p.m. (day collection),
      and from 9 p.m. to 9 a.m. (night collection); a further fasting (spot) urine
      sample was obtained at 9 a.m. at the end of the night collection. The first day
      was a control day; on the second day the subjects ingested 500 mg Ca as the
      carbonate at 9 a.m. and 9 p.m. We measured pyridinoline cross-links excretion in
      all the samples, as well as hydroxyproline in the fasting urine. The Ca
      supplements lowered urinary excretion of the markers during the day (P < 0.01),
      had only a marginal effect during the night, but reduced excretion significantly
      in the fasting urine (P < 0.001). In the whole 24-hour period, the falls in
      resorption markers were small but comparable to those seen after the ingestion of
      1 g of Ca in the evening. We conclude that the acute administration of 0.5 g Ca
      in the morning and evening reduced the markers of bone resorption in early
      postmenopausal women during the day but not during the following night, whereas
      the single 1 g supplement had the reverse effect. Over the 24-hour period, there
      was nothing to choose between the two regimes. Women at this stage in their life
      cycle probably require a larger Ca supplement if they are not taking estrogen.

PMID- 11289692
TI  - Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal
      women.
AB  - Osteoporosis is one of the most common skeletal disorders affecting
      postmenopausal women. The purpose of this study was to investigate whether a 24
      week program of aerobic high-impact loading exercise was beneficial for enhancing
      physical fitness and bone mineral density (BMD) in osteopenic postmenopausal
      women. Forty-three postmenopausal women aged 48-65 years participated in this
      study. The BMD of the spine (L2-L4) and right femoral neck of each woman was
      below 1 SD of the mean of premenopausal women, as examined by dual X-ray
      absorptiometry. The assignment of subjects into exercise or control group was not
      randomized but based on each subject's anticipated compliance to the 6-month long
      exercise program. Twenty-two subjects joined the exercise group and attended the
      training programs and 21 served as the control group. Exercise programs included
      treadmill walking at an intensity above 70% of maximal oxygen consumption
      (VO2max) for 30 minutes, followed by 10 minutes of stepping exercise using a 20
      cm-high bench. The program was conducted three times per week for 24 weeks.
      Physical fitness measurements included testing of flexibility, muscular strength
      and endurance, body composition, and cardiopulmonary fitness. The results showed
      that the quadriceps strength, muscular endurance, and VO2max in the exercise
      group had significant improvements, whereas no improvement was found in any of
      the physical fitness parameters in the control group. The BMD of the L2-L4 and
      the femoral neck in the exercise group increased 2.0% (P > 0.05) and 6.8% (P <
      0.05) and those in the control group decreased 2.3% (P < 0.05) and 1.5% (P >
      0.05), respectively. In conclusion, aerobics combined with high-impact exercise
      at a moderate intensity was effective in offsetting the decline in BMD in
      osteopenic postmenopausal women.

PMID- 11289693
TI  - Multiple cellular phenotypes in an insertional mutation in mouse affecting bone
      development.
AB  - The 6093 line of transgenic mice exhibits altered bone development as a result of
      an insertional mutation by the transgene. Female transgenic mice show a marked
      kyphosis as early as 2 weeks of age. Vertebrae from female mice have lower total
      bone area and mineral content than age-matched, gender-matched controls, although
      the bone mineral density is not changed. The femur and tibia exhibit the opposite
      effect-increased bone area and mineral content. Fluorescent bone label
      experiments indicated an increased rate of bone mineral deposition in the femur
      during the early postnatal growth period, and bone marrow from femurs of 6093
      females had increased numbers of fibroblast colony-forming units. Transgenic
      females also are obese and have altered thymocyte development, suggesting that
      the insertional mutation affects multiple cell populations. We hypothesize that
      these phenotypes arise as a result of an alteration in the function or
      developmental potential of a stromal cell or mesenchymal stem cell.

PMID- 11289694
TI  - Dual energy X-ray absorptiometry in small rats with low bone mineral density.
AB  - The feasibility of dual energy X-ray absorptiometry (DXA) using the Norland XR-26
      Mark II bone densitometer for measurements of bone mineral content (BMC) and bone
      mineral density (BMD) in small rats was evaluated. Thirty-two young, isogenic,
      Lewis rats (weights from 119 g to 227 g) were used; normal rats (n = 7) and rats
      with low BMD obtained from three different vitamin D-depleted models (n = 25).
      DXA measurements were performed using the special software for small animals.
      Duplicate scans of excised femurs performed at 2 mm/second (pixel size of 0.5 mm
      x 0.5 mm) were very precise measurements with a coefficient of variation (CV)
      below 1.6% in animals with normal BMD; in rats with low BMD, the CV was
      significantly higher (P = 0.02-0.04), 7.8% and 4.4% for BMC and BMD,
      respectively. Regression analysis demonstrated that these measurements were
      related to the ash weight (R2 > 98.6%). The CV for measurements of the lumbar
      spine at 10 mm/second (pixel size 0.5 mm x 0.5 mm) was 2.6% and 2.2% for BMC and
      BMD, respectively in rats with normal BMD, and again higher (P = 0.03-0.14) in
      rats with low BMD, 7.3% and 4.7%, respectively, for BMC and BMD. Even though low
      CVs were obtained for total body duplicate scans (scan speed of 20 mm/second and
      a pixel size of 1.5 mm x 1.5 mm), the measurements were problematic for accuracy
      because of an overestimation of both BMC and the area of bone. Using these scan
      parameters the measurements of total body bone mineral could not be recommended
      in small rats with low BMD.

PMID- 11289695
TI  - Triiodothyronine stimulates the release of membrane-bound alkaline phosphatase in
      osteoblastic cells.
AB  - Thyroid hormone deficient osteoblastic cells in cell culture released a
      significantly higher amount of alkaline phosphate (ALP) activity following T3
      replacement. T3 increased the release of total and membrane-bound ALP activity in
      these cells significantly more than T4 or inactive thyroid hormone metabolite,
      DIT. The effect of T3 on the membrane-bound ALP fraction was dose and time
      dependent; higher concentrations of T3 and longer incubation time with T3
      proportionally increased the enzyme activity. T3 had no effect on the release of
      soluble fraction of ALP. Our results indicate that in "hypothyroid" osteoblastic
      cells the total release of ALP is decreased and that the secreted fraction of ALP
      is predominantly in soluble form, whereas the addition of T3 stimulates ALP
      release and mainly increases the membrane-bound fraction. T3 also increased
      formation of actin cytoskeleton in hypothyroid osteoblastic cells. Cytochalasin
      treatment, through its inhibition of actin polymerization, produced a significant
      decrease of membrane-bound ALP release induced by T3. These data suggest that the
      regulatory role of T3 in skeletal development can partly be due to its
      stimulatory effect on the release of membrane-bound ALP by osteoblastic cells
      which is thought to be an important factor in the initiation of biological
      calcification.

PMID- 11289696
TI  - Magnesium and fluoride distribution in human cementum with age.
AB  - Sixty-two human teeth, obtained from subjects aged 11 to 80 years, were used to
      determine the magnesium and fluoride concentration and distribution with age in
      human cementum. Transverse sections were prepared from the root region of teeth.
      Samples, each 30 microm thick, were abraded in sequence from the cementum surface
      and the cemento-dentine junction by an abrasive micro-sampling technique.
      Magnesium concentrations were lower in the cementum surface, and increased
      towards the cemento-dentine junction (CDJ), while fluoride concentrations were
      higher in cementum surfaces and tended to decrease towards CDJ. Fluoride
      distribution patterns were similar to that reported earlier while average
      fluoride concentration increased with age, however, either no change or
      decreasing tendencies were observed with magnesium.

PMID- 11289697
TI  - Dentin sialoprotein (DSP) has limited effects on in vitro apatite formation and
      growth.
AB  - Sialoproteins such as bone sialoprotein (BSP) and dentin sialoprotein (DSP)
      accumulate at the mineralization fronts in bone and dentin, respectively,
      suggesting they have some function in the mineralization process. BSP, a highly
      phosphorylated protein rich in polyglutamate repeats, is an effective nucleator
      of hydroxyapatite (HA) formation in vitro. The present study examines the effect
      of DSP, a low phosphorylated but related sialoprotein, on the formation and
      growth of HA. In vitro, in a gelatin gel diffusion system, DSP at low
      concentrations (<25 microg/ml) slightly increased the yield of HA formed at 3.5
      and 5 days, while at higher concentrations (50-100 microg/ml) it slightly
      inhibited accumulation. Fewer mineral crystals were formed in the presence of
      high concentrations of DSP but they tended to aggregate (making them appear
      larger by electron microscopic analysis) than those formed in DSP-free gels. X
      ray diffraction line broadening analysis failed to show significant changes in c
      axis crystal dimensions with increasing DSP concentration. When HA-seed crystals
      were coated with DSP before inclusion in the gelatin gel there was a reduction in
      mineral accumulation relative to HA-seeds which had not been coated with DSP, but
      the extent of inhibition was significantly less than that seen in this system
      with other mineralized tissue matrix sialoproteins, such as osteopontin or BSP.
      The low affinity of DSP for well-characterized seed crystals and the limited
      effect of this protein on HA formation and growth suggest that the role of DSP in
      dentin is not primarily that of a mineralization regulator.

PMID- 11289698
TI  - Rapid embedding protocol for visualizing bone mineral and matrix.

PMID- 11289699
TI  - PTH treatment: safety studies needed.

PMID- 11289701
TI  - Antiestrogenicity of clarified slurry oil and two crude oils in a human breast
      cancer cell assay.
AB  - Exposure to crude oil and certain petroleum products can be a serious health
      hazard. Clarified slurry oil (CSO) is a complex mixture of hydrocarbons derived
      from the processing of crude oil, and is a known systemic and developmental
      toxicant, mutagen, and carcinogen. In the present study, CSO and two crude oils,
      Belridge heavy crude oil (BHCO) and Lost Hills light crude oil (LHLCO), were
      examined for their estrogenic and antiestrogenic properties in a human breast
      cancer cell (MCF-7) assay. The MCF-7 focus assay is based on postconfluent cell
      growth and tissue restructuring, measured as the postconfluent development of
      multicellular nodules or foci. The mutagenicity indices of BHCO and LHLCO also
      were determined in a modified Ames Salmonella assay. Oil samples were prepared in
      dimethyl sulfoxide, resulting in extraction of virtually all of the aromatic
      compounds including the sulfur- and nitrogen-substituted three- to seven-ring
      polycyclic aromatic compounds comprising 62.2% of the CSO, 9% of the BHCO, and 2%
      of the LHLCO by total weight. None of the three samples was estrogenic in the MCF
      7 focus assay. In contrast, all of the samples were antiestrogenic; that is, they
      inhibited the development of foci induced by 1 nM 17beta-estradiol (E2). The
      potencies of the oil samples for both antiestrogenicity and mutagenicity were
      correlated with the percent of polycyclic aromatic compounds they contained. Two
      potential mechanisms for the observed antiestrogenicity were examined.
      Radiometric analysis of the catabolism of [3H]E2 in MCF-7 cell cultures
      demonstrated that all three samples increased catabolism of E2. Results from a
      whole-cell estrogen-receptor (ER) binding assay suggested that metabolites of
      compounds in the oil samples might have competed with [3H]E2 for ER in the MCF-7
      cultures. Thus the antiestrogenicity of the oil samples may occur through at
      least two mechanisms, increased catabolism of E2 and antagonistic binding to ER.

PMID- 11289700
TI  - Influence of propylthiouracil treatment on oxidative stress and nitric oxide in
      Basedow disease patients.
AB  - Oxidative stress parameters and nitric oxide (NO) values were determined in 27
      newly diagnosed Basedow patients before and after 1 mo of propylthiouracil (PTU)
      therapy and in 15 healthy controls. Basedow patients exhibited increased
      triiodothyronine (T3) and thyroxine (T4) and decreased thyroid-stimulating
      hormone (TSH) values compared to controls. Significantly higher thiobarbituric
      acid-reactive substances (TBARS), NO and glutathione (GSH) levels, and CuZn
      superoxide dismutase (CuZn SOD) activity were found in Basedow patients in
      comparison to controls, regardless of sex. Treatment with PTU (3 x 100 mg/d for
      30 d) was effective in decreasing T1 and T4 and increasing TSH levels.
      Significantly decreased NO and TBARS and increased GSH and CuZn SOD levels were
      observed in PTU-treated Basedow patients compared to pre-PTU administration. PTU
      treated patients compared to controls still exhibited significantly higher T3 and
      lower TSH values and higher NO, TBARS, GSH, and CuZn SOD levels. The induced
      antioxidant defense and decrease in NO) values in response to PTU therapy
      emphasizes the role of PTU as an antithyroid drug, where the ability to diminish
      hyperthyroidism results in decreased catabolism and lower oxidant generation.

PMID- 11289702
TI  - Effects of daily dermal application of DEET and epermethrin, alone and in
      combination, on sensorimotor performance, blood-brain barrier, and blood-testis
      barrier in rats.
AB  - DEET and permethrin were implicated in the development of illnesses in some
      veterans of the Persian Gulf War. This study was designed to investigate the
      effects of daily dermal application of these chemicals, alone or in combination,
      on the permeability of the blood-brain barrier (BBB) and blood-testes barrier
      (BTB) and on sensorimotor performance in male Sprague-Dawley rats. Groups of five
      rats were treated with a dermal daily dose of 4, 40, or 400 mg/kg DEET in ethanol
      or 0.013, 0.13, or 1.3 mg/kg permethrin in ethanol for 60 d. A group of 10 rats
      received a daily dermal dose of ethanol and served as controls. BBB permeability
      was assessed by injection of an iv dose of the quaternary ammonium compound
      [3H]hexamethonium iodide. While permethrin produced no effect on BBB
      permeability, DEET alone caused a decrease in BBB permeability in brainstem. A
      combination of DEET and permethrin significantly decreased the BBB permeability
      in the cortex. BTB permeability was decreased by treatment with DEET alone and in
      combination with permethrin. The same animals underwent a battery of functional
      behavior tests 30, 45, and 60 d after exposure to evaluate their sensorimotor
      abilities. All treatments caused a significant decline in sensorimotor
      performance in a dose- and time-dependent manner. These results show that daily
      dermal exposure to DEET, alone or in combination with permethrin, decreased BBB
      permeability in certain brain regions, and impaired sensorimotor performance.

PMID- 11289703
TI  - Antagonistic interactions among nephrotoxic polycyclic aromatic hydrocarbons.
AB  - Although the liver and pulmonary toxicity of polycyclic aromatic hydrocarbons
      (PAHs) has been extensively characterized, limited data concerning the
      nephrotoxic potential of these chemicals are available. The present studies were
      conducted to define the kidney cell-specific toxic responses to anthracene
      (ANTH), benzo[a]pyrene (BaP), and chrysene (CHRY). Given that exposure to
      environmental chemicals from a specific source is rarely limited to a single
      compound, a second goal was to evaluate the nephrotoxic potential of binary and
      ternary mixtures of these chemicals. Cultured rat glomerular mesangial cells
      (rGMCs) and porcine cortico-tubular epithelial kidney cells (LLCPK-1) were
      challenged with hydrocarbon concentrations ranging from 0.03 to 30 microM for up
      to 24 h and were processed for measurements of mitochondrial membrane
      permeability, trypan blue dye exclusion, cytoplasmic enzyme leakage, and protein
      synthesis. BaP induced a threefold increase in mitochondrial fragility, a modest
      increase in cellular death, and 40% decrease in the rate of protein synthesis in
      rGMCs. Anthracene was also cytotoxic to rGMCs, inducing a twofold increase in
      mitochondrial fragility and a 40% decrease in the rate of protein synthesis, but
      no changes in cellular viability. Although CHRY was devoid of toxicity to rGMCs,
      a 40% decrease in the rate of protein synthesis was observed in LLCPK-1 cells
      treated with this hydrocarbon. BaP and ANTH were not overtly cytotoxic to LLCPK-1
      cells at any of the concentrations tested. Binary and ternary mixtures of BaP
      with ANTH and CHRY in rGMCs, and mixtures of CHRY with ANTH and BaP in LLCPK-1
      cells, yielded antagonistic interactions. Based on these data, it is concluded
      that PAHs exhibit chemical- and cell-specific nephrotoxicity, but that
      toxicological outcomes are influenced by the presence of multiple hydrocarbons in
      complex mixtures.

PMID- 11289704
TI  - Effects of indole-3-carbinol on immune responses, aberrant crypt foci, and
      colonic crypt cell proliferation in rats.
AB  - Male Sprague-Dawley rats were treated orally with indole-3-carbinol (13C) for 7
      wk at levels of 150, 100, and 50 mg/kg body weight. The rats were injected with
      10 mg/kg body weight of the colon carcinogen, azoxymethane (AOM) on d 2 and 9 of
      13C treatment. At termination of the study, all rats were assessed for immune
      function (humoral immunity, specific cell-mediated immunity, and nonspecific cell
      mediated immunity). Colonic tissue was collected and examined for the presence of
      aberrant crypt foci (ACF) and proliferation of crypt cells. Antibody responses to
      antigen challenge were significantly suppressed in the animals exposed to the
      high dose of 13C. Delayed-type hypersensitivity responses, natural killer cell
      activity, the number and multiplicity of ACF, and cell proliferation parameters
      were not significantly different from those of the controls. Therefore, there was
      no clear protective or enhancing effect of 13C on ACF numbers or colonic cell
      proliferation indices. There was no strong correlation between changes in immune
      responses and the preneoplastic biomarkers of colon cancer.

PMID- 11289705
TI  - Endogenous levels of C-C chemokines MIP-1alpha, MIP-1beta, and RANTES do not
      reflect the disease course in HIV-seropositive individuals.
AB  - It has been shown that the beta (C-C) chemokines macrophage inflammatory protein
      1alpha/beta (MIP-1alpha/beta) and RANTES, which are released by CD8+ T cells, are
      potent inhibitors of HIV viral replication in vitro. To investigate whether serum
      concentrations of these chemokines reflect such a protective effect in vivo, we
      measured these in peripheral blood of 60 HIV seropositive patients, 10 healthy
      subjects, and 10 disease controls. Values were compared with the CDC disease
      stages and immunological surrogate markers of disease progression, such as CD4+
      count, beta2-microglobulin and 5'-neopterin serum levels. In addition, HIV RNA
      was measured in sera. All three chemokines were not significantly different
      between HIV patients and healthy individuals, nor were differences of chemokine
      levels between the CDC stages significant. Instead, disease controls exhibited
      significantly more MIP-1alpha and MIP-1beta than normals or HIV patients.
      Furthermore, within the HIV-seropositive subjects we did not observe any
      relationship with the surrogate markers of HIV disease, CD4+ count, CD4+/CD8+
      ratio, beta2-microglobulin, and 5'-neopterin (all correlations NS). HIV viral
      load did not correlate with the measured chemokine concentrations (r < 0.1, NS).
      In conclusion, endogenous levels of MIP-1alpha, MIP-1beta, and RANTES do not
      reflect the hypothesized protective effect on disease progression in HIV
      infection. Thus, despite potential beneficial effects of the investigated
      chemokines, other factors may equally contribute to HIV replication control in
      vivo.

PMID- 11289706
TI  - Plasma endothelin-1 levels in liver cirrhosis.
AB  - The role of circulating endothelin- , a potent vasoconstricting peptide, in liver
      cirrhosis is still controversial. It has been postulated that endothelin-1 may
      play a role in the circulatory derangement occurring in cirrhotic subjects, and
      increased plasma endothelin-1 levels have been reported in these patients. In
      this study we looked for a relationship between the severity of the liver disease
      according to Child's classification and plasma endothelin-1 concentrations in a
      group of cirrhotic patients compared with a healthy control group. Twenty-two
      cirrhotic patients and 10 healthy controls, matched for sex and age, were
      selected for study after informed consent. The etiology of cirrhosis was
      posthepatitis B in 8 of 22 cases, posthepatitis C in 13 of 22 cases, and
      alcoholism in 1 patient. According to Child's classification, 6 patients were in
      class A, 6 in class B, and 10 in class C. Plasma endothelin-1 was measured by a
      commercial RIA kit (Amersham UK). Mean +/- SD plasma endothelin-1 levels were 8.8
      +/- 0.9 pg/ml in controls and 9.2 +/- 1.1 pg/ml in all cirrhotic patients (P >
      0.05). In each sub-group of cirrhotics, plasma endothelin- was 8.6 +/- 1.2 pg/ml
      in Child A, 8.9 +/- 1.9 pg/ml in Child B, and 10.6 +/- 1.5 pg/ml in Child C
      groups, respectively. There were no statistical differences between control
      subjects and Child A and B cirrhotic patients (P > 0.05). A significant increase
      in endothelinl was observed only in the Child C group versus either group A or B
      (P = 0.004). Our results show that alterations of circulating endothelin-1 do not
      occur in all cirrhotic patients; higher plasma levels than controls are only
      detectable in patients with more-severe hepatic failure. We do not know whether
      increased endothelin-1 levels are a consequence of hemodynamic disorders
      occurring in the advanced phase of liver cirrhosis or play a pathogenic role.

PMID- 11289707
TI  - Antigastric autoantibodies in Helicobacter pylori infection: role in gastric
      mucosal inflammation.
AB  - The aim of the study was to ascertain whether there is an association between the
      presence of serum parietal cell autoantibodies (PCA) and: (1) Helicobacter pylori
      infection; (2) the presence and degree of gastritis and intestinal metaplasia;
      and (3) the H. pylori infecting strain. Gastric mucosal biopsies were obtained
      from 49 consecutive patients in order to assess and grade gastritis, make a
      histological diagnosis, and culture and genotype H. pylori. H. pylori infection
      was present in 26 patients (group 1), had been present in 17 patients (group 2),
      and the remaining 6 (group 3) had never had the infection. The infecting strain
      was cagA positive in 21 of 26 group 1 patients. Positive PCA results were found
      in 84%, 76%, and 14% of patients in groups 1, 2, and 3, respectively. PCA results
      were correlated with anti-H. pylori antibody titers (P<0.05). In group 2
      patients, PCA were associated with the degree of antral gastritis (Fisher's exact
      test P<0.05). cagA status was not associated with the presence of PCA (chi2=0.68,
      NS). The frequency of positive findings for PCA in group 2 was higher in patients
      with (90%) than in those without (50%) intestinal metaplasia. IN CONCLUSION: (1)
      H. pylori infection is associated with the production of PCA, which, after
      eradication of the infection, persist and might contribute to the persistent
      antral chronic gastritis and intestinal metaplasia; (2) the gastric lesions
      associated with infections sustained by the more-virulent H. pylori strains do
      not appear to be due to the induction of antigastric autoantibodies.

PMID- 11289708
TI  - Angiotensin converting enzyme DD genotype affects  the changes of plasma
      plasminogen activator inhibitor-1 activity after primary percutaneous
      transluminal coronary angioplasty in acute myocardial infarction patients.
AB  - Angiotensin converting enzyme (ACE) DD genotype, and plasminogen activator
      inhibitor (PAI-1) 4G/4G genotype have been reported to affect PAI-1 activity in
      control subjects and atherosclerotic patients, but no data are available on the
      influence of angiotensin II type 1 receptor (AT1R) A1166C polymorphism on the
      inhibitor levels. The degree of fibrinolytic activation after percutaneous
      transluminal coronary angioplasty (PTCA) has been found to affect the risk of
      restenosis. The aim of this study was to investigate the possible influence of
      ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms on the changes of PAI-1
      activity after primary successful percutaneous transluminal angioplasty. In 29
      consecutive acute myocardial infarction patients, undergoing primary successful
      angioplasty, genotyping of ACE I/D, AT1R A1166C, and PAI-1 4G/5G polymorphisms
      was performed by polymerase chain reaction and restriction fragment length
      polymorphism analysis, and PAI-1 plasma activity (chromogenic method) was
      assessed before and after angioplasty. Following angioplasty, PAI-1 activity
      increased in 10 of 29 patients and decreased or remained unchanged in 19 of 29.
      ACE DD genotype was significantly (P = 0.04) associated with an increase of PAI-1
      activity post angioplasty (OR DD/ID+II = 6.5, CI 95% 4.83-8.22). Whereas no
      effect of PAI-1 4G/5G and AT1R A1166C polymorphisms on PAI-1 response to
      angioplasty was demonstrated, these data suggest that renin-angiotensin system
      genes are involved in the regulation of the fibrinolytic response to balloon
      injury, possibly affecting angiotensin converting enzyme activity. This
      interaction between the renin-angiotensin system and hemostasis may be a
      mechanism by which ACE DD genotype affects the risk of restenosis after
      percutaneous transluminal angioplasty.

PMID- 11289709
TI  - Cigarette smoking as an aggravating factor in inflammatory tissue-destructive
      diseases. Increase in tumor necrosis Factor-alpha priming of peripheral
      neutrophils measured as generation of oxygen radicals.
AB  - Stimulated neutrophils from subjects with various inflammatory tissue-destructive
      conditions, such as periodontal, pulmonary, gastrointestinal, and cardiovascular
      diseases, generate more oxygen radicals and proteases, implicated in tissue
      destruction, than neutrophils from healthy persons. Cigarette smoking aggravates
      these diseases. The aim of our study was to investigate the effect of cigarette
      smoking on the priming capacity of tumor necrosis factor-alpha, measured as
      generation of radicals from stimulated neutrophils, in smoking and non-smoking
      subjects with or without periodontitis. The priming effect was higher in
      neutrophils from smokers. In the group with periodontitis, smoking caused an even
      greater increase in the generation of radicals, indicating an additive effect of
      this local disease. The membrane expression of CD11b, CD15, and CD63 was
      significantly higher on neutrophils from smokers, indicating upregulated
      neutrophil functions. This increased priming effect of tumor necrosis factor
      alpha in smokers subjects could be of importance in the aggravation of tissue
      destructive inflammatory diseases.

PMID- 11289710
TI  - Bovine seminal RNase induces apoptosis in normal proliferating lymphocytes.
AB  - Bovine seminal ribonuclease is a member of the RISBAses (ribonucleases with
      special biological actions) family. It exerts specific anti-tumor, embryotoxic,
      aspermatogenic and immunosuppressive activities. The cytotoxic effect of bovine
      seminal ribonuclease on tumor cells is accompanied by the induction of apoptosis.
      We provide ultrastructural and flow cytometry evidence of apoptotic death
      following bovine seminal ribonuclease treatment, in normal cells and
      phytohemagglutinin-stimulated lymphocytes. Transmission and scanning electron
      microscopy, which were fully supported by flow cytometry data, showed typical
      features of apoptosis, such as decreased cell size, chromatin condensation,
      fragmentation in micronuclei, and the presence of apoptotic bodies.

PMID- 11289711
TI  - Assay of erythrocyte membrane fatty acids. Effects of storage time at low
      temperature.
AB  - The study of the stability of saturated mono-, or polyunsaturated fatty acids,
      both esterified and not esterified, in plasma, circulating cells, and tissues is
      extremely important to validate the use of biological samples stored at low
      temperature in "biological banks", which are used for experimental,
      observational, dietary, or pharmacological studies. Since red blood cells are
      easily accessible cells, they are used as a marker of less-accessible tissues,
      especially in large-scale epidemiological studies. Data from the literature
      suggest that the addition of an antioxidant and the freezing of red blood cells
      do not cause any variation in the fatty acid composition for a period of 2-6
      months up to 1 year. We evaluated the fatty acid concentration in red blood cells
      isolated from venous blood samples of one subject, preserved with butylated
      hydroxytoluene and N2 and stored at -80 degrees C for up to 2 years. Erythrocytes
      of venous samples of six subjects stored at -20 degrees C for 6 months without
      butylated hydroxytoluene and in the presence of air were used for comparison
      purposes. Our data demonstrate that a long storage time (2 years) does not
      significantly influence the erythrocyte fatty acid concentration when using very
      low temperatures (-80 degrees C) and antioxidants (butylated hydroxytoluene) in
      the presence of N2.

PMID- 11289712
TI  - Lack of association of fibrinogen, lipoprotein(a), and albumin excretion rate
      with low birthweight.
AB  - An excess of cardiovascular morbidity has been related to low birthweight. The
      aim of this study was to evaluate the relationship between low birthweight and
      levels of fibrinogen, lipoprotein(a), and albumin excretion rate, which are known
      risk factors for coronary artery disease. Seventy-two twins, with the same within
      pair gender and normal glucose tolerance, were analyzed in order to avoid
      confounding factors, such as gestational age, birth order, or sex. Twins with the
      highest birthweights within the couple showed no significant difference of
      fibrinogen, lipoprotein(a), and albumin excretion rates compared with the twins
      with the lowest birthweights among the two co-twins. Moreover, no relevant
      correlation was found between birthweight and intra-pair birthweight differences
      and fibrinogen, lipoprotein(a), and albumin excretion rates. The lack of
      correlation between fibrinogen, lipoprotein(a), albumin excretion rate and
      birthweight, suggests that these factors do not contribute to the link between
      intrauterine malnutrition and increased cardiovascular risk.

PMID- 11289713
TI  - Gender-specific haplotype association of collagen alpha2 (XI) gene in
      ossification of the posterior longitudinal ligament of the spine.
AB  - Among Japanese, ossification of the posterior longitudinal ligament of the spine
      (OPLL) is a leading cause of myelopathy, showing ectopic bone formation in the
      paravertebral ligament. We have provided genetic evidence that the collagen
      alpha2 (XI) (COL11A2) locus of chromosome 6 constitutes susceptibility for OPLL.
      Five distinct single nucleotide polymorphisms (SNPs), identified in COL11A2, were
      combined to construct possible haplotypes by the use of a maximum likelihood
      program. Estimated haplotype frequency was compared in OPLL patients and non-OPLL
      controls. We report a gender-specific association of the COL11AA2 haplotvpe with
      OPLL. The frequency of the most commonly observed haplotype was significantly
      higher in male patients (P = 0.0003) compared with controls, but not in female
      patients (P = 0.21). OPLL is predominantly observed in males. with a prevalence
      ratio of 2:1, and our gender-specific associations indicate that genetic factors
      involving COL11A2 play a specific role in the etiology of OPLL exclusively in
      males.

PMID- 11289714
TI  - IQGAP1, a negative regulator of cell-cell adhesion, is upregulated by gene
      amplification at 15q26 in gastric cancer cell lines HSC39 and 40A.
AB  - Our previous comparative genomic hybridization (CGH) study revealed a novel
      amplified region at 15q26 in two cell lines established from diffuse types of
      gastric cancer (GC). In this amplified region, FES and IGF1R, known targets on
      15q26, were located telomeric to the amplicon in the two cell lines, HSC39 and
      40A, suggesting that another tumor-associated gene exists in this region. While
      screening expressed sequence tags (ESTs) for novel genes in this region, we
      identified the IQGAP1 amplification. IQGAP1 has been reported to encode a ras GAP
      related protein, and its interaction with cadherin and/or beta-catenin induces a
      dissociation of beta-catenin from the cadherin-catenin complex, one of the
      mechanisms for cell-cell adhesion. Northern and Western blot analyses revealed
      that amplification of this gene was accompanied by corresponding increases in
      mRNA and protein expression. Moreover, immunocytochemical staining showed that
      overexpressed IQGAP1 accumulated at the membrane, suggesting its colocalization
      with beta-catenin. Taken together, these findings suggest that IQGAP1 may be one
      of the target genes in the 15q26 amplicon correlated with a malignant phenotype
      of gastric cancer cells, such as diffuse and invasive characteristics, through
      the disruption of E-cadherin-mediated cell-cell adhesion.

PMID- 11289715
TI  - Association analysis of polymorphisms in the upstream region of the human
      dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits.
AB  - The human dopamine D4 receptor (DRD4) is of major interest in molccular studies
      of schizophrenia and personality traits. We examined the association of
      schizophrenia and polymorphisms in the upstream region of the DRD4 gene (-768G>A
      in the negative modulator region; -521C>T, -376C >T, and -291C>T in the cell type
      specific promoter region; and -616C>G between the two regions) in 208
      schizophrenic patients and 210 normal controls. No significant difference in
      genotype and allele frequencies was observed between the two groups, indicating
      that these polymorphisms do not make a major contribution to the pathogenesis of
      schizophrenia. We also studied the association of polymorphisms in the upstream
      region and a 48-bp repeat polymorphism in exon III of the DRD4 gene with
      personality traits in 173 Japanese individuals who completed the temperament and
      character inventory (TCI). The -768G>A polymorphism was significantly associated
      with reward dependence (P= 0.044), while no significant association was observed
      between novelty seeking and polymorphisms in the upstream region or the exon III
      repeat polymorphism of the DRD4 gene.

PMID- 11289716
TI  - Five novel single-nucleotide polymorphisms of human interferon gamma identified
      by sequencing the entire gene.
AB  - Interferon gamma (IFNG) plays important roles in the regulation of bone
      remodelling. We describe here six single-nucleotide polymorphisms (SNPs) in the
      IFNG gene, five of which are novel, and their allelic frequencies in the Japanese
      population, as determined by sequencing 48 alleles of the entire gene. Four of
      these polymorphisms were identified inside the third intron, at nucleotide (nt)
      positions 2459 (A/G), 2671 (T/C), 3177 (T/G), and 3273 (G/A). In exon 4, SNPs
      were identified at nt positions 5199 (A/T) and 5272 (A/G). These polymorphic
      sites will be useful for genetic studies of disorders that affect the
      inflammatory process or calcium metabolism.

PMID- 11289717
TI  - Nine novel single-nucleotide polymorphisms in the integrin beta4 (ITGB4) gene in
      the Japanese population.
AB  - We identified nine single-nucleotide polymorphisms (SNPs) in the human integrin
      beta4 (ITGB4) gene (17q24-q25), which encodes a cell-surface receptor, by
      screening all exons and exon-intron boundaries. Seven of these SNPs were present
      in coding regions and two in intronic sequences; four of the coding SNPs involved
      amino-acid substitutions. As the gene is implicated in the tumorigenesis of
      breast cancers, the polymorphic sites will serve as useful markers not only for
      distinguishing alleles in loss of heterozygosity (LOH) analyses but also for
      studying genetic susceptibility to malignancies in humans.

PMID- 11289718
TI  - Correlation of genetic etiology with response to beta-adrenergic blockade among
      symptomatic patients with familial long-QT syndrome.
AB  - Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be
      responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that
      entails a high risk of sudden death. beta-Adrenergic blocking agents are the
      first therapeutic choice, and 80% of patients treated with these agents show
      symptomatic relief; however the remaining 20% do not respond well. We previously
      performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and
      identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present
      retrospective study, we found that patients carrying mutations in the KCNQ1 gene
      responded better to beta-adrenergic blocking agents than those with KCNH2
      mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good
      example of the power of genetic diagnosis to direct the selection of appropriate
      therapy for patients with diseases of heterogeneous genetic etiology.

PMID- 11289719
TI  - A novel activating mutation (C129S) in the calcium-sensing receptor gene in a
      Japanese family with autosomal dominant hypocalcemia.
AB  - Autosomal dominant hypocalcemia can be caused by activating mutations of the
      calcium-sensing receptor (CaSR) gene. We experienced two patients (proband and
      her daughter) with hypocalcemia caused by a missense mutation of the CaSR gene.
      The proband, aged 25, showed hypocalcemia and hypoparathyroidism from infancy.
      She had been diagnosed as having idiopathic hypoparathyroidism and had been
      treated with calcitriol. She gave birth to a female infant at age 24 years. Her
      daughter was found to have hypocalcemia (Ca, 6.6mg/dl), without seizure or
      tetany, when she was 7 months old. DNA analysis of their CaSR genes showed a
      novel heterozygous mutation at codon 129 (TGC-to-AGC) with substitution of
      cysteine for serine (C129S). Familial examination revealed that this mutation had
      occurred de-novo in the proband. Wild-type and niutant (C129S) CaSR cDNA were
      transfected into HEK293 cells, and intracellular calcium concentrations were
      measured with a fluorescent calcium indicator. HEK cells transfected with the
      C129S mutant CaSR gene showed a larger increase in intracellular calcium
      concentration in response to the change in the extracellular calcium
      concentration than HEK cells transfected with the wild-type receptor. We conclude
      that the C129S mutation in the CaSR gene observed in these patients causes
      autosomal dominant hypocalcemia.

PMID- 11289720
TI  - alpha-1-Antichymotrypsin gene A1252G variant (ACT Isehara-1) is associated with a
      lacunar type of ischemic cerebrovascular disease.
AB  - alpha-1-Antichymotrypsin (ACT) is a plasma protease inhibitor belonging to the
      serpine superfamily; it has many functions. and thus qualitative change in ACT is
      likely to result in specific diseases. We previously reported a variant AACT (ACT
      Isehara-1, Met389Val, A1252G) in patients with ischemic cerebrovascular disease
      (CVD). The present study was designed to examine the association of the variant
      with ischemic CVD, in 87 patients and 397 age-matched controls. We found that the
      frequency of the A1252G variant (ACT Isehara-1) was higher in the group with
      ischemic CVD than in the control group (P = 0.0397), which appeared to be
      independent of known risk factors. We subdivided the CVD group into lacunar and
      atherothrombotic subgroups. Further analysis by subtype of ischemic CVD showed an
      association of ACT Isehara-1 with lacunar infarction (P = 0.0036). These results
      suggest that ACT lsehara-1 is a new genetic risk factor for ischemic CVD,
      especially lacunar-type infarction, in Japan.

PMID- 11289721
TI  - Novel single nucleotide polymorphisms of the human colony-stimulating factor 2
      (CSF2) gene identified by sequencing the entire gene.
AB  - We describe three single nucleotide polymorphisms (SNPs) of the human colony
      stimulating factor 2 (CSF2) gene and their allelic frequencies, as determined by
      direct sequencing of 48 alleles of the entire CSF2 gene. Three polymorphisms were
      identified, at nucleotide positions 1816 (T/C), 2284 (C/T), and 3079 (G/A). These
      polymorphisms will be useful in genetic studies not only of hematologic disorders
      but also of disorders of bone metabolism.

PMID- 11289722
TI  - Associations of distinct variants of the intestinal mucin gene MUC3A with
      ulcerative colitis and Crohn's disease.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD), the major forms of inflammatory
      bowel diseases (IBDs). are multifactorial disorders of unknown etiology. We
      reported a possible association of rare variable number of tandem repeat (VNTR)
      alleles of the "MUC3" gene with a susceptibility to UC. However, an entire
      structure of "MUC3" is still unknown because the long stretches of tandem repeats
      in this "gene" make its cloning extraordinarily difficult. In this study, we
      report evidence that "MUC3" consists of two genes, MUC3A and MUC3B, both of which
      encode membrane-bound mucins with two epidermal growth factor-like motifs, and we
      describe the complete 3'-terminal structures of these two genes. We have also
      analyzed the single nucleotide polymorphisms (SNPs) in the exonic sequences of
      the 3' portions of these two genes to investigate whether sequence variations in
      these regions can cause person-to-person differences in the susceptibility to
      IBDs, and report here that non-synonymous SNPs of MUC3A, involving a tyrosine
      residue with a proposed role in cell signaling, may confer genetic predisposition
      to CD (P = 0.0132). Our findings suggest that variants of MUC3A may be involved
      in the occurrence of UC and CD in distinct manners.

PMID- 11289723
TI  - Novel single nucleotide polymorphisms of the human nuclear factor kappa-B 2 gene
      identified by sequencing the entire gene.
AB  - The nuclear factor kappa-B 2 (NFKB2) gene is a member of the NFKB/Rel gene
      family, which is known to be a pivotal regulator of the acute phase of the
      inflammatory response and of immune responses. We identified three novel single
      nucleotide polymorphisms (SNPs) and determined their allelic frequencies, as
      determined by the sequencing of 48 alleles of the entire gene in a Japanese
      population sample. Two of the three polymorphisms were identified at nucleotide
      (nt) position 1837 (T/C) and nt position, 1867 (GG/G) in the upstream region of
      the gene. The other polymorphism was identified at nt position 2584 (G/T) within
      intron 1. These polymorphisms will be useful in genetic studies of the processes
      involved in inflammatory responses and in bone differentiation.

PMID- 11289724
TI  - Parental predictors of teen driving risk.
AB  - OBJECTIVES: To determine the nature and prevalence of parental involvement with
      teen driving and its relationship to teen driving risk. METHODS: A statewide
      sample of 424 Maryland parents and their provisionally licensed teenagers were
      interviewed. RESULTS: Parents were unaware of the extent to which their teens had
      engaged in high-risk traffic events, such as being distracted by friends or
      driving too fast. Teens who were allowed unsupervised access to a car at least
      several times a week were 3 times as likely to have driven too fast than were
      those who had access once a month or less. The frequency of parental teaching of
      driving skills was not strongly related to teen risk taking. CONCLUSION: The need
      to increase parents' capacity to impose and enforce driving restrictions on
      provisionally licensed teen drivers is indicated.

PMID- 11289725
TI  - Health-oriented behaviors: their implication in attending for breast cancer
      screening.
AB  - OBJECTIVE: To assess the implication of health-oriented behavior and state of
      health variables estimated to influence women's participation in a breast cancer
      screening program. METHODS: A sample of 512 participants and 196 nonparticipants
      was taken from a total of 60,908 women between 45 and 65 years of age. RESULTS:
      There are significant differences in women's perception of their knowledge of
      breast cancer, estimated prognosis, and reasons for not performing self
      examination. The nonparticipant group reports more health problems. CONCLUSION:
      The study assesses the relative contribution of these variables to participation
      levels, although further empirical testing of all these issues is recommended.

PMID- 11289726
TI  - Fruit and vegetable intake and weight-control behaviors among US youth.
AB  - OBJECTIVE: To examine the relationship between fruit and vegetable intake and
      weight control behaviors among youth. METHODS: Data (N = 16,262) were derived
      from the 1997 national school-based Youth Risk Behavior Survey (YRBS). RESULTS:
      Results indicated that adolescents in this study, especially females, were at
      risk for inadequate fruit and vegetable intake. Weight-control behaviors were
      high especially among females. CONCLUSION: Although some weight-control behaviors
      may be hazardous, adolescents who were practicing weight-control behaviors
      engaged in the positive dietary behavior of consuming more servings of fruits and
      vegetables.

PMID- 11289727
TI  - Examination of the transtheoretical model and exercise in 3 populations.
AB  - OBJECTIVE: To examine differences in the processes of change and self-efficacy
      for exercise across the stages of change in 3 populations to determine its
      suitability for use in diverse groups. METHODS: Cross-sectional survey design
      with population as a between-subjects variable: high school students (n = 168),
      university undergraduate students (n = 215), and employed adults (n = 63).
      RESULTS: ANOVAs revealed main effects of stage (p < .0001) and population (p <
      .001) in process use and self-efficacy but no population by stage interaction.
      CONCLUSIONS: The consistency of patterns of the TTM variables supports its
      potential for effective intervention in diverse populations.

PMID- 11289729
TI  - Perceived health needs of inner-city street prostitutes: a preliminary study.
AB  - OBJECTIVE: To survey inner-city prostitutes' perceived health needs. METHODS: One
      hundred forty street prostitutes in Washington DC, were surveyed to determine
      their perceived health needs, in addition to levels of post traumatic stress
      disorder (PTSD). RESULTS: The final sample comprised 100 individuals,
      representing 3 subgroups of prostitutes, female, male, and transgender male.
      Major health needs included protection from physical and sexual assault, social
      support, counseling, addictions treatment, job training, and medical care. Over
      42% of the population was identified as meeting established criteria for PTSD.
      CONCLUSION: Effective program development for inner-city prostitutes needs to
      acknowledge the presence of distinct subpopulations and the pervasive influence
      of PTSD on health status.

PMID- 11289728
TI  - Physical activity behaviors of adolescents in public and private high schools.
AB  - OBJECTIVE: To examine physical activity differences between public (PUBHS) and
      private (PVTHS) high school students (n = 6,627). METHODS: The 1995 SC Youth Risk
      Behavior Survey was utilized. Chi-square analyses compared PVTHS and PUBHS
      students. RESULTS: PVTHS school students reported greater involvement in regular
      exercise programs (p < .001) and participation on school-based sport teams (p <
      .001). However, PUBHS school students reported greater participation in physical
      education (p < .001). PUBHS males participated in more community-based sport
      programs than did PVTHS males (p <.001); however, PVTHS females participated in
      more community-based sports than PUBHS males did (p < .001). CONCLUSION:
      Significantly different physical activity behaviors exist between PVTHS and PUBHS
      students in South Carolina.

PMID- 11289730
TI  - Equity in the diagnosis of chest pain: race and gender.
AB  - OBJECTIVE: To explore gender and racial equity in emergency room treatment of
      chest pain. METHODS: Three hundred seventy-nine patient records were analyzed,
      taking into account effects of age, clinic, comorbid status, and insurance
      status. RESULTS: Analysis of covariance and logistic regression revealed
      statistically significant differences between races but not between genders for
      time to first EKG and percent of patients receiving cardiac catheterization and
      echocardiography. Blacks waited longer than whites for an EKG and were less
      likely to receive cardiac catheterizations but more likely to receive
      echocardiography. CONCLUSION: This study demonstrates a lack of equity by race in
      treatment of chest pain emergencies.

PMID- 11289731
TI  - Analysis of data from complex survey designs.

PMID- 11289732
TI  - Facets: computer software for evaluating assessment tools.

PMID- 11289734
TI  - Thyroid cytology and histology.
AB  - Fine needle aspiration (FNA) is an economical procedure that allows prompt
      evaluation of a thyroidal mass. Careful attention to each step of the aspiration
      will allow good specimens to be obtained. The cytopathologist should obtain the
      aspirates or else should accompany the clinician performing the aspirations.
      Unsatisfactory specimens should constitute less than 5% of the total. Reliable
      diagnoses can be made of papillary carcinoma, medullary carcinoma, anaplastic
      carcinoma, chronic lymphocytic thyroiditis, benign cystic lesions and the usual
      colloid-rich adenomatoid nodules. The diagnosis of follicular neoplasms and some
      cellular adenomatoid nodules remains problematical. Therefore, some thyroid
      operations inevitably yield benign follicular lesions.

PMID- 11289733
TI  - Molecular pathogenesis of thyroid nodules and cancer.
AB  - Tumours derived from the thyroid follicular epithelium represent an informative
      model for understanding the molecular pathogenesis of multistage tumourigenesis,
      which is the prevailing theory on cancer development and progression nowadays.
      The early stages of thyroid tumour development appear to be the consequence of
      the activation or 'de novo' expression of several proto-oncogenes or growth
      factor receptors, such as ras, ret, NTRK, met, gsp and the thyrotropin (TSH)
      receptor. Alterations in the expression pattern of these genes are associated
      with the development of differentiated neoplasms, ranging from benign toxic
      adenomas (gsp and TSH receptor), to follicular (ras) and papillary (ret/PTC,
      NTRK, met) carcinomas. They may all be considered to be early events of thyroid
      cell transformation and, for some, experimental evidence derived from gene
      transfer studies supports this hypothesis. Alterations in tumour suppressor genes
      (p53, Rb) are associated instead with the most aggressive and poorly
      differentiated forms of thyroid cancer, indicating that, in the thyroid
      tumourigenic process, they represent late genetic events. Specific environmental
      factors (iodine deficiency, ionizing radiations) have been shown to play a
      crucial role in promoting the development of thyroid cancer, influencing both its
      genotypic and phenotypic features. Interestingly, a high percentage of genetic
      lesions causing thyroid cancer originate from gene rearrangements and chromosomal
      translocations (ret/PTC, NTRK, Pax-8/PPARgamma) a finding which, being a rare
      event in most epithelial tumours, makes the molecular pathogenesis of thyroid
      cancer unique. The uninterrupted flow of information on the molecular genetics of
      thyroid nodules and cancer will broaden the correlation between genotype and
      phenotype and will also provide important information for the development of more
      accurate preoperative diagnostic tools and more efficient treatment choices for
      the different forms of thyroid cancer.

PMID- 11289735
TI  - Thyroid nodules: pathogenesis, diagnosis and treatment.
AB  - Thyroid nodules are very frequently found and their prevalence steadily increases
      with age. The discovery of such lesions by high-resolution radiological imaging
      procedures that have been performed for other indications raises the problem of
      how incidentally discovered thyroid nodules should be investigated in a cost
      effective manner to identify the rare patient with a clinically significant
      malignancy. In this review the clinical criteria that prompt the evaluation of
      thyroid nodules are discussed, as is the currently recommended diagnostic
      approach, which principally relies on fine needle aspiration biopsy. The clinical
      implications of the different cytological diagnoses are discussed, with a special
      emphasis on the management of indeterminate, microfollicular lesions. Finally,
      the evidence for and against suppressive thyroid hormone therapy for benign
      thyroid nodules and multinodular goitres is discussed, with particular
      consideration of high-risk patients with prior external radiation therapy to the
      neck region.

PMID- 11289736
TI  - Multinodular goitre: 'much more to it than simply iodine deficiency'.
AB  - For over a century, multinodular goitre (MNG) has been looked upon as the simple
      consequence of iodine deficiency. This view is now no longer tenable. Indeed,
      many characteristics of MNG do not fit with the iodine deficiency concept. For
      example, nodular goitre is a frequent disease even in those countries where the
      population is never exposed to iodine shortage. Moreover, neither
      multinodularity, nor the proverbial heterogeneity of growth and function or the
      autonomous, thyroid stimulating hormone (TSH)-independent growth of many goitres
      are compatible with the iodine deficiency concept, let alone subclinical or overt
      thyrotoxicosis which often complicates the course of a MNG. Recent investigations
      have led to the conclusion that MNGs are true benign neoplasias that are due to
      the high intrinsic growth potential of a variable, genetically predetermined
      fraction of all thyrocytes. Gross and heritable metabolic and functional
      differences between the individual thyrocytes, from which new follicles are
      generated during goitrogenesis, are the cause of the often spectacular functional
      and structural heterogeneity of MNG. Superimposed iodine deficiency changes the
      epidemiology, but not the basic mechanisms of goitrogenesis. These new
      pathogenetic concepts have a profound impact on the clinical management of MNG.

PMID- 11289737
TI  - Papillary and follicular thyroid carcinoma.
AB  - Papillary and follicular thyroid carcinomas are among the most curable of all
      cancers. However, some patients are at high risk of recurrence or even death from
      their cancer. Most of these patients can be identified at the time of diagnosis
      using well-established prognostic indicators. The extent of initial treatment and
      follow-up should therefore be individualized. The early discovery of persistent
      and recurrent disease is based on the combined use of serum thyroglobulin
      determination and of total body scanning with 131I. The recent availability of
      recombinant human thyroid stimulating hormone has greatly improved the quality of
      the patient's life during follow-up. Treatment of recurrences is based mainly on
      surgery and 131I treatment.

PMID- 11289739
TI  - Diagnosis and treatment of medullary thyroid cancer.
AB  - Medullary carcinoma of the thyroid (MTC) is a rare tumour derived from thyroid C
      cells with serum calcitonin as a specific and sensitive marker. MTC is inherited
      in 25% of cases, with an autosomal dominant transmission, age-related penetrance
      and variable expressivity. MTC is an obligatory component of multiple endocrine
      neoplasia type 2 (MEN2), which comprises three well defined syndromes: MEN2A,
      which may be associated with pheochromocytoma and/or hyperparathyroidism; the
      much rarer MEN2B, which occurs early and is accompanied by developmental
      abnormalities; while in contrast, familial MTC (FMTC) is not associated with any
      endocrinopathy. The RET proto-oncogene is the causative gene of the MEN2
      syndromes and mutations in this gene are found in >90% of inherited cases,
      allowing easier and more reliable family screening than pentagastrin stimulation
      tests. Nevertheless, the correlation between the genotype and the different
      clinical phenotypes is not perfect. The prognosis of MTC depends on its staging
      at presentation, and the early appearance of cervical lymph node metastases
      emphasizes the need for extensive surgery, although many patients still do not
      normalize calcitonin levels post-operatively, and they remain a challenge for the
      further management.

PMID- 11289738
TI  - Management of undifferentiated thyroid cancer.
AB  - Management of thyroid carcinoma relies upon the tumour cells maintaining the
      differentiated functions that are typical of normal thyroid follicular cells,
      such as: dependence upon thyrotropin for growth, production of thyroglobulin and
      effective transport of iodine. Likewise, differentiated thyroid carcinomas often
      exhibit an auspicious clinical behaviour with a slow rate of growth and low
      potential for invasion and distant metastasis. These features permit therapy of
      disseminated tumour, effective follow-up surveillance and the assumption of a
      good prognosis. As each of these features are lost, the opportunities for both
      disease status assessment and therapeutic intervention diminish accordingly. A
      major obstacle is our failure to define effective systemic treatments to replace
      radioiodine therapy, whose loss is consonant with the loss of iodine transport
      and retention. The extreme of undifferentiated clinical behaviour is epitomized
      by anaplastic thyroid carcinoma, a rare, terminally dedifferentiated malignancy
      that is rapidly and invariably fatal. It is important to be attuned to clinical
      clues suggesting the presence of dedifferentiated tumour and related prognostic
      signs. This allows the application of currently limited therapeutic options and
      defines the need for research to develop new systemic treatments.

PMID- 11289740
TI  - Surgical approach to thyroid nodules and cancer.
AB  - Fine needle aspiration cytology is the mainstay of the diagnostic work-up of
      solitary thyroid nodules. Together with the patient's history and the clinical
      findings, cytology determines the indication for surgery. The minimal
      intervention for a suspicious nodule consists of thyroid lobectomy. If a
      diagnosis of malignancy is established, then we recommend total thyroidectomy for
      all follicular lesions that are larger than 1.5 cm and for high-risk papillary
      tumours. Near-total thyroidectomy may be appropriate for low-risk patients with
      papillary carcinoma in whom it is not intended to use radioactive iodine
      ablation. Whereas ipsilateral lymphadenectomy of the central (primary)
      compartment should routinely be performed, modified radical neck dissection is
      only indicated in evident nodal disease of the lateral (secondary)
      compartment(s). Patients with incidentally discovered differentiated thyroid
      carcinomas generally do not require complete thyroidectomy unless the tumours are
      larger than 1.5 cm in diameter or nodal involvement is present. A detailed
      description of the surgical technique for thyroidectomy and lymphadenectomy is
      given and an overview of surgical complications is provided.

PMID- 11289741
TI  - Post-Chernobyl thyroid carcinoma in children.
AB  - The dramatic increase in childhood thyroid carcinoma observed in Belarus and
      Ukraine as early as 4 years after the Chernobyl nuclear accident, is well
      recognized as being a consequence of exposure to radioactive iodine fallout.
      Uncertainties persist concerning the contamination and the dosimetric data.
      Thyroid nodule, cervical lymph nodes or systematic ultrasound thyroid screening
      in exposed children led to the diagnosis. The carcinomas affected younger
      subjects, were less influenced by gender, and were more aggressive at clinical
      and histological presentation than in the case with naturally occurring
      carcinoma. Total thyroidectomy and radioiodine treatment remain the treatment of
      choice. The prognosis is good but further studies are needed to evaluate the
      prognosis of children presenting with pulmonary metastasis. The project of the
      Newly Independent States Chernobyl Tissue Bank will facilitate molecular genetic
      research into this important public health issue. Nevertheless, clinicians must
      keep in mind the simplicity and the effectiveness of iodine prophylaxis.

PMID- 11289744
TI  - IDEALFirst: electronic pre-publication for the EJSO.

PMID- 11289745
TI  - Autonomic nerve damage in rectal cancer surgery.

PMID- 11289746
TI  - Multimodal treatment of peritoneal carcinomatosis and sarcomatosis.
AB  - Peritoneal carcinomatosis and sarcomatosis (PCS) are short-term fatal conditions
      amenable only to palliative treatment. They are generally considered as a
      systemic disease at clinical presentation, and are resistant to standard
      treatments. However, there may be in the natural history a phase of loco-regional
      tumour spread during which the tumour may still be curable. Surgical treatment
      alone, or in combination with systemic chemotherapy, has yielded poor results in
      terms of survival and quality of life. One approach is cytoreductive surgery (CS)
      combined with the intraperitoneal administration of antiblastic agents. This may
      diminish any residual tumour following macroscopic excision and may overcome the
      pharmacokinetic limits of systemic chemotherapy. A further improvement in this
      multimodal approach may be achieved by the use of hyperthermic intraperitoneal
      intraoperative chemotherapy (HIIC). Results so far have been encouraging.
      However, series reported in the literature are relatively small and
      heterogeneous, and clinical and technical factors which include the selection of
      patients, optimal drugs dosage and temperature, evaluation of outcome and costs
      are still under discussion.

PMID- 11289747
TI  - Variations in diagnostic and therapeutic procedures in a multicentre, randomized
      clinical trial (EORTC 10853) investigating breast-conserving treatment for DCIS.
AB  - AIMS: To evaluate the diagnostic and therapeutic procedures which were followed
      in a European Organization for Research and Treatment of Cancer (EORTC)
      randomized clinical trial investigating the role of radiotherapy in breast
      conserving treatment (BCT) for ductal carcinoma in situ (DCIS) of the breast.
      METHODS: The medical files of 824 of the 1010 randomized patients (82%) were
      reviewed during site visits to 30 participating institutes. RESULTS: Large
      variations occurred, particularly in the surgical procedures and
      histopathological work-up which were performed. Important risk factors like
      tumour size and margin status were poorly quantified in the medical files.
      CONCLUSIONS: These findings emphasize the need for establishing uniform
      guidelines for diagnostic and therapeutic procedures for DCIS, and for clearly
      defined risk factors for recurrence after BCT for DCIS. Because of its randomized
      nature, the main question of the trial, i.e. the effect of radiotherapy on the
      risk of local recurrence, will not be influenced by variation. The risk of local
      recurrence in itself, and hence the success of BCT for DCIS, may however be
      influenced by the quality of the initial procedures that were conducted.

PMID- 11289748
TI  - Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of
      sentinel lymph nodes in breast cancer patients.
AB  - AIM: The purpose of the present study was to evaluate the usefulness of gamma
      probe and ultrasonographically-guided fine-needle aspiration biopsy (FNAB) in the
      pre-operative detection of sentinel node (SN) metastasis in breast cancer
      patients. METHODS: Sentinel node biopsy (SNB) was performed in patients with
      stage I or II breast cancer with clinically negative nodes using dye and radio
      isotope. Axillas of 60 patients in whom a hot spot was detected by gamma probe
      were examined by ultrasonography. Pre-operative diagnosis of SN metastasis by
      gamma probe and ultrasonographically-guided FNAB was compared with the
      histological results of SN. RESULTS: The sensitivity, specificity and overall
      accuracy of ultrasonography in the diagnosis of SN metastasis were 50.0%, 92.1%
      and 76.7%, respectively. SNs were visualized by ultrasonography in 29 of 60
      patients. Of 14 patients with positive results by ultrasonography, four had
      positive and two had negative cytology. The combination of ultrasonography and
      ultrasonographically-guided FNAB for visualized nodes had a sensitivity of 78.5%,
      specificity of 93.3% and overall accuracy of 86.2%. Blind FNAB in the hot spot
      was not useful in the detection of SN metastasis in patients whose SNs failed to
      be detected by ultrasonography. CONCLUSIONS: Gamma probe and ultrasonographically
      guided FNAB is a potentially useful method for pre-operative detection of SN
      metastasis. In patients with positive SNs, SNB is not indicated and complete
      axillary lymph-node dissection can be performed as a primary procedure.

PMID- 11289749
TI  - Angiosarcoma after conservative treatment and radiation therapy for
      adenocarcinoma of the breast.
AB  - Radio-induced angiosarcoma of the breast after conservative therapy for invasive
      adenocarcinoma is a very rare tumour. Between 1996 and 2000, four cases were
      operated in our Department of Surgical Oncology. After a review of the literature
      over the same period of time, natural history and treatment of radio-induced
      angiosarcomas of the breast were analysed.

PMID- 11289750
TI  - Pre-operative oestradiol levels - relation to survival in breast cancer.
AB  - AIMS: There are clinical observations that operation during the luteal phase of
      the menstrual cycle (with high oestradiol levels) may positively influence
      prognosis in breast cancer. However, few studies have information on plasma
      levels of hormones pre-operatively. METHODS: We studied 774 women treated for
      breast cancer where plasma levels of oestradiol had been measured 1-2 days pre
      operatively. Date and cause of death were ascertained from the files of the
      Swedish Cancer Register and 5434 person-years were observed. The endpoint was
      death with breast cancer as the underlying cause (n=41 and n=158 in the pre- and
      post-menopausal group, respectively). RESULTS: In life-table analyses, only pre
      menopausal patients with oestradiol 500 pmol/l and above had a tendency (not
      statistically significant) for better survival. Multivariate Cox models with
      oestradiol modelled in continuous form yielded relative hazards (RH) close to
      unity in all women and in strata according to menopausal status. CONCLUSIONS:
      When oestradiol was analysed in categorized form, only women with the highest
      levels had a tendency for improved prognosis (RH around 0.7; not statistically
      significant). Moreover, this pattern was not apparent for pre-menopausal women.
      Our findings contradict the notion that the pre-operative oestradiol level is
      independently associated with breast cancer prognosis.

PMID- 11289751
TI  - Thyroid malignancy in endemic nodular goitres: prevalence, pattern and treatment.
AB  - AIMS: The epidemiology of thyroid cancers in goitre endemic zones has not been
      recently reviewed, and changes being currently reported have been from studies in
      non-endemic areas. The aims of this study were to present the clinical pattern of
      thyroid malignancy in a goitre endemic area and identify recent changes, if any.
      METHODS: The study was conducted at Obafemi Awolowo University Teaching Hospitals
      Complex, Ile-Ife, Nigeria between January 1983 and December 1993. Records of
      patients with nodular goitres treated with thyroidectomy were reviewed, and the
      clinical features, laboratory parameters, treatment, outcome and follow-up of
      histologically-proven malignant cases were studied. RESULTS: Thirty-six of 279
      (12.9%) patients, aged 13-85 years (mean)=43.7+/-14.7 years), carried malignant
      goitres, and most (80%) were young or middle-aged women. Of the well
      differentiated cancers, follicular type was the most prevalent, being six- and 12
      fold as frequent as papillary and medullary cancers (69%vs 11% and 5.6%),
      respectively. Lymphoma accounted for 5.6%, fibrosarcoma, 5.6% and anaplastic,
      2.8%. No relationship was demonstrable between cancer type, duration of goitre
      and age at diagnosis (r=0.06 and 0.17, respectively). CONCLUSIONS: Thyroid
      cancers afflict comparatively young women in our environment, and follicular
      cancer remains the predominant type, partly as a result of persisting dietary
      iodine deficiency.

PMID- 11289752
TI  - Familial medullary thyroid carcinoma (FMTC). Study of one family (treatment
      criteria).
AB  - AIM: The nosology of familial medullary thyroid carcinoma (FMTC) has been
      described as a distinct pathology, genetically determined and with autosomal
      dominant transmission with a gene penetrance of almost 100%. The diagnosis of
      this morbid condition can be made if at least four members of the same family are
      affected by calcitonin-secreting C-cell carcinoma. METHODS AND RESULTS: We report
      the analysis of a family in which FMTC was diagnosed between 1993 and 1998. Of
      the five patients we confirmed as being affected by FMTC, we were able to perform
      a prophylactic thyroidectomy in only one case. The high possibility of lymph-node
      metastasis at the time of clinical diagnosis (52-75%), and the high morbidity and
      radio-chemo-resistance to adjuvant therapies, indicate total thyroidectomy with
      central lymph-node dissection. CONCLUSION: It appears that preventive
      lymphadenectomy does not substantially improve survival, while pre-clinical
      diagnosis is of greater importance than surgery in improving survival and
      preventing recurrence. Total preventive thyroidectomy has been recommended in all
      carriers of ret genetic defects, even in families at risk with mutations of the
      618 or 620 codon, because the penetrance of FMTC approaches 100%, and a 100%
      accordance between presence of the disease and gene carrier status is reported.
      This procedure would therefore represent the only possibility of achieving a 100%
      cure in subjects affected by familial medullary thyroid carcinoma.

PMID- 11289753
TI  - Long-term outcome of urinary function after extended lymphadenectomy in patients
      with distal rectal cancer.
AB  - AIMS: Extended lymphadenectomy for rectal cancer has been superseded by autonomic
      nerve-sparing surgery, but it still has historical significance. It is useful to
      document the long-term outcome of urinary function in cases who had resection of
      the inferior hypogastric nerve plexus (pelvic nerve plexus). METHODS: The long
      term urinary function following extended lymphadenectomy was studied
      retrospectively through the medical records of 83 patients who had been followed
      up for more than 5 years after surgery. RESULTS: Forty-four per cent of the male
      patients and 17% of the female patients had to perform clean intermittent self
      catheterization (CIC) for more than 1 year; these rates were almost the same at 3
      years after the procedure. Urinary incontinence was reported in 34% of the male
      patients and 45% of the female patients. Complicated cystitis (eight patients),
      complicated pyelonephritis (two patients), bladder stones (five patients) that
      required surgical treatment, and chronic renal failure (two patients) were
      considered as adverse outcomes of extended surgery. In particular, one case
      needed to undergo urinary diversion. CONCLUSIONS: A surprisingly large proportion
      of patients suffered various urinary tract problems due to extended
      lymphadenectomy. The findings demonstrate the importance of selection of well
      balanced operations that can encompass both radicality and quality of life. The
      extent of resection should be decided by the extent of the cancer and routine
      excision of the inferior hypogastric nerve plexus should not be performed.

PMID- 11289754
TI  - nm23 protein expression in colorectal carcinoma metastasis in regional lymph
      nodes and the liver.
AB  - AIMS: The nm23 gene has been shown to have metastasis suppressing activity and
      abnormalities of the gene or its expression may be important in tumour
      progression and dissemination. This study was set out to investigate the possible
      role of the nm23 in colorectal adenocarcinoma dissemination by examining the
      level of nm23 protein expression in colorectal carcinoma metastasis in regional
      lymph nodes and the liver. METHODS: Using a monoclonal antibody, NCL-nm23
      (Novocastra), immunohistochemical expression of the nm23 protein was examined in
      cases of metastatic colorectal adenocarcinoma in regional lymph nodes (n=71) and
      liver (n=36). RESULTS: The cases of lymph-node metastasis also had tissues from
      the primary carcinoma (n=71) and matching normal non-neoplastic mucosal tissues
      (n=71) from the colon and rectum available for the study. More than half of the
      cases of primary colorectal carcinoma (43/71; 60%) displayed strong nm23
      immunoreactivity, with a similar proportion of the lymph-node metastases (40/71
      cases; 56%) having strong nm23 immunostaining. However, only a small minority of
      the normal controls of non-neoplastic colorectal epithelia (12/71 cases; 17%) had
      strong nm23 immunoreactivity. The difference in nm23 protein expression between
      normal colorectal mucosa and primary colorectal carcinoma was statistically
      significant (P=0.0001; chi-squared test with continuity correction). However, no
      significant difference in nm23 protein expression was found between primary
      colorectal carcinoma and lymph-node metastases (P=0.81; chi-squared test with
      continuity correction). Most of the liver metastases (24/36 cases; 67%) had
      strong nm23 immunostaining but this finding was not statistically significant
      when compared with that seen in primary colorectal carcinoma (P=0.62; chi-squared
      test with continuity correction). In addition, nm23 expression was not found to
      significantly correlate with 5-year survival of patients with liver metastasis
      (P=0.86), suggesting that it had no predictive value for overall patient
      survival. There was also no significant correlation between disease recurrence
      and nm23 expression (P=0.63). CONCLUSIONS: In summary, increased nm23 protein
      immunoreactivity is seen in the majority of colorectal carcinomas when compared
      to normal colorectal tissues but no significant difference in nm23 expression was
      found between primary colorectal carcinoma and metastatic carcinoma in regional
      lymph nodes or the liver. This study suggests that increased nm23 expression may
      be important in early colorectal carcinoma but not in later progression and
      dissemination of the tumour. In conclusion, the role and importance of the nm23
      gene in the development of tumour metastasis in colorectal carcinoma is
      questionable.

PMID- 11289755
TI  - Involvement of granzyme B and perforin in suppressing nodal metastasis of cancer
      cells in breast and lung cancers.
AB  - AIMS: Granzyme B and perforin, which are contained in cytotoxic granules produced
      by tumour-infiltrating immune cells, have been reported to be involved in
      suppression of cancer progression. In this study, the relationship between
      expression of these molecules and clinical factors in cancer patients was
      studied. METHODS: Tumour tissue obtained from 23 breast cancer patients and 13
      lung cancer patients were examined for expression of granzyme B, perforin and B7
      1, using an immunohistochemical technique. The percentage of cells positive for
      expression of these molecules and the clinical status of each case were compared.
      RESULTS: Both granzyme B and perforin were distributed in the cytoplasm of cancer
      cells in many cases rather than in tumour-infiltrating lymphocytes. This was
      observed even in cases of early-stage tumours. In both breast and lung cancer
      patients, the percentage of cells positive for granzyme B and perforin expression
      was inversely correlated with the status of regional node metastasis. A
      competitive RT-PCR analysis confirmed that the expression of mRNA from these
      molecules extracted from the tumours was consistent with the immunohistochemical
      results. CONCLUSION: Granzyme B and perforin may play a role in the suppression
      of nodal metastasis of cancer cells in breast and lung cancers.

PMID- 11289756
TI  - Chylous ascites after oncological abdominal surgery: incidence and treatment.
AB  - AIMS: Chylous ascites can be a problem after oncological abdominal surgery. The
      aim of this study was to report the incidence and the management of the problem.
      METHODS: A retrospective study over a 2-year period of all oncological patients
      undergoing abdominal surgical procedures was carried out. Patients with
      resections in the upper abdomen and retroperitoneum were studied in more detail.
      RESULTS: Twelve (7.4%) of 163 patients with complex surgical procedures developed
      a chyloperitoneum. Chylous ascites stopped in time with conservative management
      in nine patients. Three patients had a peritoneovenous shunt inserted with
      success. No relaparotomies to ligate leaking intestinal lymph vessels were
      necessary.

PMID- 11289757
TI  - Regional plus systemic chemotherapy: an effective treatment in recurrent non
      small cell lung cancer.
AB  - AIMS: This study was undertaken to determine the activity and toxicity of
      regional chemotherapy using an isolated thoracic perfusion (ITP) technique as
      second-line treatment for patients with advanced and recurrent non-small cell
      lung cancer (NSCLC). METHODS: Eighteen patients with relapsed NSCLC confined to
      the thoracic region entered the study and received regional chemotherapy using
      ITP plus low-dose systemic chemotherapy. All 18 patients had been pre-treated
      with some form of chemotherapy, surgery and/or radiotherapy. The cytostatic
      regimen had two components: (1) ITP using mitomycin 10 mg/m(2), navelbine 25
      mg/m(2)and cisplatin 30 mg/m(2)on day 1; (2) systemic chemotherapy with 5
      fluorouracil 250 mg/m(2)and cisplatin 20 mg/m(2)given as a continuous infusion
      over 24 h on days 1-4. RESULTS: All 18 patients were assessable for toxicity,
      tumour response and survival. There were 10/18 responses (CR 0; PR 10): a
      response rate of 56%. Side-effects were transient and acceptable. No treatment
      related death occurred. Median survival was 21 months and the 1-year survival
      rate was 75%. CONCLUSIONS: Regional chemotherapy using ITP plus low-dose systemic
      chemotherapy is effective in recurrent advanced NSCLC, with an encouraging
      survival outcome.

PMID- 11289758
TI  - Reconstructive surgery in spinal tumours.
AB  - AIMS: This study reports 21 patients who underwent reconstructive surgery for
      destructive spinal tumours. MATERIALS AND METHODS: The mean age was 49 years
      (range: 39-71 years). Primary lesions were met in two cases. Secondary spinal
      tumours were diagnosed in 19 cases. Thirteen were breast carcinoma metastases
      (61.9%). The cervical spine was involved in four cases, thoracic spine in six
      cases, and the lumbar spine in 11 cases. One patient underwent decompression
      laminectomy and posterior pedicle screw stabilization. The others underwent
      tumour tissue excision, with spinal reconstruction with autogenous bone grafting,
      with or without vertebral body replacement prosthesis. Anterior and posterior
      stabilization of the vertebral column was also used. RESULTS: The objectives of
      surgery were achieved, in that early ambulation, easier nursing care, pain relief
      and neurological recovery were reported in all cases. No surgery-related
      complications were encountered. CONCLUSIONS: We recommend surgical intervention
      for such lesions where reasonable longevity is anticipated.

PMID- 11289759
TI  - Recurrence of curetted and bone-grafted giant-cell tumours with and without
      adjuvant phenol therapy.
AB  - AIMS: Giant-cell tumour of bone (GCT) represents 5% of all primary bone tumours.
      The aim of this study was to compare the outcome of GCT treated with or without
      phenol. METHODS: Out of 53 patients primarily treated for a giant-cell tumour, 47
      were followed, with a median follow-up of 11 (range 4-43) years. All patients
      were disease-free at the latest follow-up. Of the 40 tumours (85%) located in
      long bones, 14 (35%) were treated by curettage and bone grafting and 12 (30%) by
      additional adjuvant phenol treatment. Fourteen patients (35%) received different
      therapies, including en-bloc resection, endoprosthesis, cement packing or other
      therapy. RESULTS: There were seven (17.5%) recurrences in long bones after a
      median of 12 (range 4-60) months, three (3/14, 21%) in the group treated without
      phenol and three (3/12, 25%) in the group with phenol. Of the seven tumours
      located in the axial skeleton, two patients died within the first year after
      surgery. The remaining five patients were followed, with a median follow-up of 12
      (range 8-23) years. No patients had metastases or a multicentric tumour.
      CONCLUSIONS: Despite the different rates of recurrence reported in literature,
      this study suggests that local recurrence rate of giant-cell tumours located in
      long bones treated with or without phenol is similar. Adequate removal of the
      tumour seems to be a more important predictive factor for the outcome of surgery
      than the use of phenol as an adjuvant therapy.

PMID- 11289760
TI  - Evaluation of putative molecular biomarkers in abdominal and retroperitoneal
      leiomyosarcomas.
AB  - AIMS: Leiomyosarcomas (LMS) are diverse tumours with different biological
      behaviour. To evaluate the biological nature of intraabdominal and
      retroperitoneal leiomyosarcomas we retrospectively examined the immunoreactivity
      of p53, bcl-2 and proliferative activity expressed as Ki-67-labelling index in 43
      tumours. METHODS: Immunohistochemical staining was performed using a peroxidase
      streptavidin method on paraffin-embedded sections using specific anti- p53, anti-
      bcl-2 and anti Ki-67 monoclonal antibodies. RESULTS: Of 43 tumours, seven were
      located in the stomach, 11 in the small or large bowel, 12 in the uterus, 11 in
      the retroperitoneum and two cases in the urinary bladder. Five-year disease-free
      survival was 46.5%. Twenty-three patients (53.4%) died of the disease. Positive
      immunoreactivity for p53 and bcl-2 was found in 18 (41.9%) and 26 patients
      (60.5%), respectively. Positive Ki-67 staining was observed in eight patients
      (18.6%). Proliferative indices were higher in LMS with high mitotic activity
      (P=0.004) and high grade (P=0.009). All Ki-67 positive LMS were intermediate or
      high-grade tumours. Ki-67-labelling index showed inverse relationship to bcl-2
      expression. A trend towards higher survival and expression of bcl-2, p53 or Ki-67
      was found. CONCLUSIONS: Our results demonstrate that p53 and bcl-2 are expressed
      in a substantial number of intraabdominal and retroperitoneal leiomyosarcomas. In
      our study, the expression of these biomarkers did not predict patient outcome.
      Higher Ki-67 labelling indices were found in more biologically aggressive
      leiomyosarcomas.

PMID- 11289761
TI  - Mitochondrial DNA, human evolution and the cancer genotype.
AB  - Mitochondrial DNA is a small, well characterized chromosome which is transmitted
      across the generations in the maternal lineage, independently of nuclear DNA.
      mtDNA acts in effect as a robust, species specific biological clock and tracer
      which can be used to follow the evolution and spread by geographic migration of
      populations from their origins. Mutations in mtDNA cause specific maternally
      hereditable diseases, and can be used for forensic purposes. They are not
      specifically implicated in neoplasia, but they may provide clues as to the nature
      and origins of cancer susceptibility in various populations.

PMID- 11289762
TI  - Surgical technique: submuscular placement of breast implant ports with delayed
      expansion following ultrasound localization.
AB  - Immediate or delayed reconstruction is offered to most women after mastectomy as
      standard care in the UK. Many women choose breast reconstruction with an implant
      alone or in conjunction with a myocutaneous flap. The most recent generation of
      biodimensional anatomical permanent expanders has permanent ports for delayed
      saline inflation. In slim women, the subcutaneous placement of the port and
      tubing may be unsightly and cause symptoms of pain and chaffing. We describe a
      technique of inserting the permanent port deep to a muscular layer on the chest
      wall to avoid these problems. This technique has been used in five satisfied
      patients, with a mean body mass index of 24.0 (range 21.7-25.5) kg/m(2). The mean
      follow-up was 9.4 (range 5-14) months with no complications or problems. The port
      placement technique we describe is effective and facilitates permanent
      implantation for long-term access.

PMID- 11289763
TI  - Diffuse malignant mesothelioma of the peritoneum following abdominal
      radiotherapy.
AB  - Two cases of diffuse malignant mesothelioma of the peritoneum are described in 65
      and 54-year-old patients a long time following abdominal radiotherapy treatment
      for testicular tumour in addition to orchidectomy.

PMID- 11289764
TI  - Successful removal of a giant recurrent chondrosarcoma of the thoracic wall in a
      patient with hereditary multiple exostoses.
AB  - Chondrosarcoma represents the most common malignant tumour of the chest wall,
      with a tendency for local recurrence after resection. Here we report the
      successful complete resection of a giant, local recurrent chondrosarcoma of the
      chest wall (max. diameter 25 cm), in a patient with hereditary multiple
      exostoses, who had had a wide resection 8 years before. Clinical features and
      surgical management are described.

PMID- 11289765
TI  - Anaphylaxis to patent blue dye during sentinel lymph node biopsy for breast
      cancer.

PMID- 11289766
TI  - Medullary carcinoma of the thyroid with serotonin production and carcinoid-like
      syndrome.

PMID- 11289767
TI  - Surgical face masks in the operating theatre: re-examining the evidence.
AB  - In most modern hospitals, no one is allowed to enter the operating theatre
      without wearing a surgical face mask. The practice of wearing masks is believed
      to minimize the transmission of oro- and nasopharyngeal bacteria from operating
      theatre staff to patients' wounds, thereby decreasing the likelihood of
      postoperative surgical site infections. In this era of cost-restraints, shrinking
      hospital budgets, and evidence-based medicine, many health care professionals
      have begun to re-examine traditional infection control practices. Over the past
      decade, studies challenging the accepted dogma of surgical face mask usage have
      been published. Masks that function as protective barriers are another emerging
      issue. Due to a greater awareness of HIV and other blood-borne viruses, masks are
      taking on a greater role in protecting health care workers from potentially
      infectious blood and body fluids. The purpose of this review is to evaluate the
      latest evidence for and against routine use of surgical face masks in the
      operating theatre.

PMID- 11289768
TI  - Infection control in Danish healthcare: organization and practice.

PMID- 11289769
TI  - Source and route of methicillin-resistant Staphylococcus epidermidis transmitted
      to the surgical wound during cardio-thoracic surgery. Possibility of preventing
      wound contamination by use of special scrub suits.
AB  - The objective of this study was to trace the source and route of transmission of
      methicillin-resistant Staphylococcus epidermidis (MRSE) in the surgical wound
      during cardio-thoracic surgery, and to investigate the possibility of reducing
      wound contamination by wearing special scrub suits. In total 65 elective
      operations for coronary artery bypass grafting (CABG) with or without concomitant
      valve replacement were investigated. All staff present in the operating room wore
      conventional scrub suits during 33 operations and special scrub suits during 32
      operations. Samples were taken from the hands of the scrubbed team after surgical
      scrub but before putting on sterile gowns and gloves, and from patients' skin
      (incisional area of sternum and vein harvesting area of legs) after preoperative
      skin preparation with chlorhexidine gluconate. Air samples were taken during
      operations. Samples were also taken from the wound just before closure. Total
      counts of bacteria on sternal skin and from the wound (cfu/cm2) were calculated
      as well as total counts of bacteria in the air (cfu/m3). Strains of MRSE
      recovered from the different sampling sites were compared by pulsed field gel
      electrophoresis (PFGE). It was found that wearing special scrub suits did not
      reduce the number of air-samples where MRSE was found compared with conventional
      scrub suits. The risk factor most strongly associated with MRSE in the wound at
      the end of the operation was preoperative carriage of MRSE on sternal skin; RR
      2.42 [95% CI 1.43-4.10], P= 0.021. By use of PFGE, it was possible to identify
      the probable source for four MRSE isolates recovered from the wound. In three
      cases the source was the patients own skin. Finding MRSE in air-samples, or on
      the hands of the scrubbed team, were not risk factors for the recovery of MRSE in
      the wound at the end of operation. In conclusion, with a total bacterial air
      count around 20 cfu/m3 and a low proportion of MRSE, the reduction of total air
      counts by use of tightly woven special scrub suits did not reduce air counts of
      MRSE or wound contamination with MRSE. The patients' sternal skin was the main
      source for wound contamination with MRSE

PMID- 11289770
TI  - Transfusion transmitted virus infection in patients on maintenance haemodialysis
      and in hospital workers.
AB  - A newly discovered DNA virus, transfusion transmitted virus (TTV), was isolated
      from a post-transfusional hepatitis patient in Japan. A high prevalence (32-46%)
      of TTV infections in patients receiving maintenance haemodialysis (HD) has been
      reported but the occupational risk of TTV on HD units has not yet been
      determined. We determined the prevalence of TTV in workers in the same HD unit
      and the risk factors for TTV infection in HD patients, using logistic regression
      analysis. The prevalence of TTV DNA was 59.6% in 198 HD patients, significantly
      higher than that in the HD unit (13 of 39, 33.3%;P= 0.002) and non-HD healthcare
      workers (20 of 75, 26.7%; P= 0.001). A logistic regression analysis showed that
      male gender and negative test results for hepatitis G virus RNA were risk factors
      for TTV infection, but prior blood transfusion and duration of HD were not.
      Stepwise selection of multiple regression analysis showed that the presence of
      hepatitis C virus RNA was the only significant predictor for high serum ALT
      activity, and that the presence of TTV DNA was not. These results indicate that
      TTV is one of the prevalent human viruses transmissible either parenterally or
      nonparenterally in HD patients, but the occupational risk of TTV infection in HD
      unit workers is as low as in other healthcare workers. The pathogenic effects of
      TTV on the liver appear to be limited.

PMID- 11289771
TI  - Inactivation of hepatitis B virus in plasma by hospital in-use chemical
      disinfectants assessed by a modified HepG2 cell culture.
AB  - Because of the difficulties of the chimpanzee model and the genetic differences
      using the duck model, we developed a cell culture method to measure human
      hepatitis B virus (HBV) inactivation in vitro. Pooled HBV-infected human plasma
      that had been exposed to a disinfectant was left in contact for three days with a
      cell culture of the human hepatoma cell line, HepG2, with 4% polyethyleneglycol
      and 3 mM sodium butyrate. The mean log10 of the viral titre of unexposed plasma
      was 4.87 infectious units per mL. Our results showed that 1% glutaraldehyde,
      sodium hypochlorite at 4700 ppm free chlorine and an iodophor-detergent
      disinfectant containing 3.6% povidone-iodine reduced viral titres by factors
      exceeding 10(3)-10(4). However, sodium hypochlorite at 1000 ppm free chlorine had
      minimal activity and povidone-iodine at 9, 5 and 3.6% had no measurable activity
      (less than 10-fold reduction). This is the first study using a cell culture model
      to assess disinfectant activity against HBV. It demonstrates more rapidly than
      the chimpanzee model that glutaraldehyde and sodium hypochlorite, using standard
      concentrations and exposure times compatible with clinical practice, were highly
      active against HBV. However, unexpectedly for an enveloped virus, we found no
      antiviral activity for iodine in the absence of detergent.

PMID- 11289772
TI  - Protocol implementation in hospital infection control practice: an Italian
      experience of preoperative antibiotic prophylaxis.
AB  - This study evaluates the effectiveness of a protocol implemented to induce
      behavioural modifications in healthcare workers (HCWs). A preoperative antibiotic
      prophylaxis protocol for surgical procedures in clean and clean-contaminated
      wounds was used. The study was conducted in a 300-bed Italian university hospital
      between 1998 and 1999. The protocol's impact was analysed by retrospective
      examination of the clinical records for selected common surgical procedures. The
      study also investigated the reasons for the low compliance with the protocol
      through a focus group methodology. We examined 723 surgical procedures and the
      overall compliance was 30.8% (56/182) before the implementation of the protocol
      and 45.2% (76/168) after 1 year (P< or = 0.01). During the same period compliance
      with the use of antibiotics increased when antibiotics were recommended by the
      protocol (5/115 vs. 19/109, P< or = 0.01) and use decreased when they were not
      (51/67 vs. 57/59, P< or = 0.01). As reported in the focus groups, reasons for low
      compliance included hospital policy weaknesses in protocol definition and
      implementation and the cultural behaviour of HCWs. Our results reinforce previous
      findings that monitoring the effectiveness of protocol implementation in the
      medical care setting is essential. Critical points that might increase the
      effectiveness of protocol implementation have also been identified.

PMID- 11289773
TI  - Emergence and spread of low-level mupirocin resistance in methicillin-resistant
      Staphylococcus aureus isolated from a community hospital in Japan.
AB  - The objective of this study was to investigate the state of mupirocin resistance
      in methicillin-resistant Staphylococcus aureus (MRSA) in a community hospital in
      Japan. Ninety strains of MRSA were isolated from the respiratory tract of 56
      patients (group I, Jun 1990-Aug 1996) before introduction of mupirocin in Japan,
      which were compared with 168 strains from 48 patients (group II, Sept 1996-Jan
      1998) and 146 strains from 85 patients (group III, Feb 1999-Dec 1999) isolated
      after introduction of mupirocin. Comparisons were made by determining the minimum
      inhibitory concentrations (MIC) against nine antibiotics. Fifty-five MRSA
      isolates from 27 patients [13 (27.1%) of 48 in group II and 14 (16.5%) of 85 in
      group III] after introduction of mupirocin showed low-level resistance to
      mupirocin (MIC, 6.25 to 50 microg/ml) but the remaining isolates were sensitive
      to mupirocin (MIC < or =3.13 microg/ml). Most patients colonized with low-level
      mupirocin-resistant MRSA were elderly (> or =65 years of age), on total
      parenteral nutrition or nasal feeding and had other underlying diseases. The
      proportion of patients colonized with low-level mupirocin-resistant MRSA
      following repeated use of mupirocin was higher in patients of group II than those
      of group III. Molecular typing by pulsed-field gel electrophoresis (PFGE)
      demonstrated that the pattern of 13 MRSA isolates from 13 patients of group II
      consisted of three patterns (A, B, C) with predominance of pattern A, while the
      pattern of 13 MRSA isolates from 13 patients of group III consisted of three
      patterns (A, C, D) with predominance of patterns A and D. Our results indicated
      that resistance of MRSA to mupirocin remains at a low level at present in Japan.
      However, we should be aware of the possible emergence of MRSA highly resistant to
      mupirocin in the future.

PMID- 11289774
TI  - Critical care unit outbreak of Serratia liquefaciens from contaminated pressure
      monitoring equipment.
AB  - Between October and December 1999, Serratia liquefaciens was isolated from 11
      patients in an adult critical care unit. One patient was infected on two separate
      occasions. In total, there were 10 positive blood cultures and five positive
      intravascular catheter tips. Eight cases were clinically infected, three were
      possibly infected and one was not. All patients with clinical isolates received
      appropriate empirical antibiotic treatment and responded well. Environmental
      investigation revealed S. liquefaciens in syringes and connector tubing used to
      calibrate the intravascular line pressure monitoring equipment of eight patients.
      Three of these patients also had clinical isolates of S. liquefaciens. Analysis
      by pulsed-field gel electrophoresis found clinical and environmental isolates to
      be of the same strain. The most likely mode of transmission was a non-sterile
      sphygmomanometer tip used daily for calibration. Inadequate microbiological
      sampling methods may have limited detection of S. liquefaciens. Several other
      examples of poor infection control techniques were identified during the
      outbreak, notably lapses in hand hygiene during intravascular pressure
      monitoring. It was also observed that unlabelled multidose heparin and insulin
      vials were shared between patients and personal hand creams were used by staff.
      However, these were not directly implicated in the outbreak. The outbreak ended
      when poor infection control practices were corrected. Calibration syringes and
      connector tubing were discarded after a single use. The sphygmomanometer was
      replaced by a pneumatic pressure transducer tester with connector tube and the
      frequency of calibration reduced to a single test following line insertion only.
      The non-disposable tube was disinfected with alcohol wipes between patients.

PMID- 11289775
TI  - Outcome in critically ill patients with candidal fungaemia: Candida albicans vs.
      Candida glabrata.
AB  - In a retrospective study (1 January 1992-12 December 1998), we investigated
      population characteristics and outcome in critically ill patients with fungaemia
      involving C. albicans (n=41) and C. glabrata (n=15). Patients with C. glabrata
      fungaemia were significantly older compared with patients in the C. albicans
      group (P=0.024). There were no other differences in population characteristics or
      severity of illness. Logistic regression analysis showed age (P=0.021), the
      presence of a polymicrobial blood stream infection (P=0.039), and renal failure
      (P=0.044) to be independent predictors of mortality. There was no significant
      difference in in-hospital mortality between the C. glabrata and C. albicans
      groups (60.0% vs. 41.5%; P=0.24). Since age was an independent predictor of
      mortality, the trend towards a higher mortality in patients with C. glabrata can
      be explained by this population being significantly older. In conclusion, we
      found no difference in mortality between patients with fungaemia involving C.
      albicans and C. glabrata.

PMID- 11289776
TI  - Dental hygienists and infection control: knowledge, attitudes and behaviour in
      Italy.
AB  - This study evaluated knowledge, attitudes and behaviour regarding infection
      control of dental hygienists in Italy. Among the 185 responders to the self
      administered mailed questionnaire, 91.3% agreed with the correct responses to the
      three questions on knowledge about infection prevention and control procedures
      chosen as an indicator of 'good' knowledge. However, 21% were uncertain whether,
      or disagreed that, dental instruments should be rinsed in water after contact
      with glutaraldehyde and 17.5% agreed that, or were uncertain whether, 10 min
      contact with glutaraldehyde provided sterilization. Only 36.5% knew all the five
      oral manifestations of acquired immunodeficiency syndrome (AIDS) (acute
      periodontal problems, candidiasis, hairy leukoplakia, herpes simplex virus,
      Kaposi's sarcoma) and this knowledge was significantly higher in dental
      hygienists with a lower number of years of practice. More than two-thirds used a
      steam sterilizer or glutaraldehyde for appropriate times and temperatures for
      disinfection/sterilization of instruments and used appropriate surface
      disinfection procedures. The correct application of disinfection or sterilization
      methods for instruments was more likely in the older respondents and in those who
      attended continuing education courses on infection control. A positive attitude
      was reported by the majority of dental hygienists who agreed that guidelines
      should be maintained and applied and was significantly more likely in younger
      respondents. Only 57.9% routinely follow all recommendations for infection
      control practices and their use was significantly higher in the older
      respondents. Educational programmes are needed for improving knowledge about oral
      manifestations of AIDS in order to support dentists to provide early diagnosis
      and about the correct use of procedures and universal precautions for preventing
      infections.

PMID- 11289777
TI  - Ventilator-associated pneumonias in a cardiothoracic surgery centre postoperative
      intensive care unit.
AB  - Cases of ventilator-associated pneumonia (VAP) were investigated in a
      cardiothoracic surgery postoperative intensive care unit between 1 January 1999
      and 31 December 1999. A total of 1716 patients who had undergone cardiothoracic
      operations and admitted to the intensive care unit (ICU) were included in the
      study. Patient- and laboratory-based prospective surveillance of VAP was done
      along with other hospital-acquired infections. During the study period a total of
      26 585 patient-days with 2708 ventilator-days were recorded. Forty-six cases of
      VAP occurred in 36 of 1716 patients who had undergone cardiothoracic operations
      (2.09%, 1.3 episodes of pneumonia per patient). The ventilator utilization rate
      at our institution was 0.10. There were 16.4 VAPs per 1000 ventilation days.
      Thirty-eight percent of VAP were caused by Gram-negative enteric rods, 34% by
      Pseudomonas aeruginosa, and 17% by Staphylococcus aureus. VAP was polymicrobial
      in 9% of cases. No causative micro-organism was identified in 2% of cases. The
      same bacteria were isolated in both blood and endotracheal aspirate cultures in
      10 of 46 pneumonia cases (22%). The crude mortality rate of VAP was calculated as
      30%

PMID- 11289778
TI  - Heterogeneity among infecting strains of Pseudomonas aeruginosa in diverse
      departments of a large Tunisian hospital.
AB  - Clinical isolates of Pseudomonas aeruginosa were obtained during a half-year
      screening period of five different wards of the La Rabta Hospital (Tunis).
      Distinct clinical isolates (N= 82) were obtained from patients, 40 (48%) of which
      originated from the Department of Otolaryngology. In order to define the local
      epidemiology of this opportunistic organism, all strains were serotyped, analysed
      for pyocin production and genetically characterized with the help of pulsed-field
      gel electrophoresis (PFGE). The data show that, despite the frequent occurrence
      of identical serotypes, most of the isolates represent unique pyocin types (N=
      53) and genotypes (N= 64). A combination of the pyocin and PFGE data showed that
      nearly all strains were of unique types, except for two pairs of strains. A
      limited number of strain clusters was observed on the basis of DNA typing data
      alone. This involved eight genotypes, some of which were clustered with respect
      to clinical environment or time. Genotype 22 occurred most frequently (6/83, 7%)
      and independently of time and locale, indicating that it may represent either a
      clonal type constituting a major fraction of all P. aeruginosa isolates in the
      region or a more prevalent organism. Despite a relatively high incidence of P.
      aeruginosa infections, the polyclonality of these strains shows that, in La Rabta
      Hospital, pseudomonal infections are not primarily due to excessive spread of a
      single bacterial genotype.

PMID- 11289779
TI  - Poor assessment of HIV epidemiology and occupational HIV transmission risk by
      medical students.
AB  - Due to the increasing global number of HIV-positive patients, the potential risk
      of acquiring infection with HIV during routine clinical care is on the increase.
      Assessments of the knowledge of medical students about occupational HIV
      transmission are therefore important. This study analysed the knowledge of 397
      first year and 75 fifth year medical students about the epidemiology of HIV in
      Germany and their assessment of the risk of acquiring HIV in different clinical
      situations. Medical students overestimated the incidence and mortality of HIV in
      Germany, with fewer than 30% knowing the correct numbers. They also overestimated
      the risk of occupational HIV infection in several clinical settings, such as
      changing dirty linen or wound dressings. Few differences were found between first
      and fifth year medical students. For their later work as physicians medical
      students still need more information and counselling about the epidemiology of
      HIV, prevention of occupational HIV infections and care for patients with
      HIV/AIDS.

PMID- 11289780
TI  - Diathermy pencils--a potential vector for the transmission of prions?

PMID- 11289781
TI  - Clustering of infections caused by different PFGE types of Stenotrophomonas
      maltophilia occurring simultaneously in a university hospital.

PMID- 11289782
TI  - Possible cross-infection with hepatitis C virus of an unusual genotype on a
      haemodialysis unit.

PMID- 11289783
TI  - The use of hand hygiene products could reduce colonization on the hands.

PMID- 11289786
TI  - Flux estimation using isotopic tracers: common ground for metabolic physiology
      and metabolic engineering.
AB  - Metabolic physiologists and metabolic engineers share the need to estimate flux.
      However, the physiologist often works with systems that do not maintain steady
      state for long. Many sites cannot be sampled, and calculating mass and isotopic
      balance for the entire system may not be feasible. To deal with these
      constraints, metabolic physiologists have developed specialized isotopic
      techniques that may be unfamiliar to metabolic engineers. A selection of these
      techniques is presented here, not because it is anticipated that they would be
      used by engineers exactly as in the physiologist's setting, but because they
      illustrate novel applications of tracer methodology. Creative engineers may find
      new adaptations of these tools in metabolic engineering and opportunities to
      increase redundancy. Physiologists, entering into a dialog with engineers, may
      see more clearly the potential of comprehensive models and revisit the
      impediments to a more complete analysis of human metabolic systems.

PMID- 11289787
TI  - Reflections on the scope and the future of metabolic engineering and its
      connections to functional genomics and drug discovery.
AB  - Concepts, experience, and tools from metabolic engineering are immediately
      applicable to the challenge of understanding how the genome influences phenotype.
      However, new experimental approaches and mathematical and computational resources
      are needed to maximize the contributions of metabolic engineering to general
      questions in functional genomics. Among the priorities are systems for studying
      physiology on a microscale, theoretical tools for understanding biological
      control systems, and metabolic simulators "in silico" which provide reasonable
      predictions of stimulus-response relationships at engineering and medical
      resolution, with incomplete information on cellular mechanisms and their
      parameters. Approaching cells as complex systems, already a well-established
      principle in metabolic engineering, is essential to surmount stagnation in the
      rate of pharmaceutical discovery which is still based on a naive single-target
      paradigm.

PMID- 11289788
TI  - The effects of feed and intracellular pyruvate levels on the redistribution of
      metabolic fluxes in Escherichia coli.
AB  - In a previous study, an Escherichia coli strain lacking the key enzymes (acetate
      kinase and phosphotransacetylase, ACK-PTA) of the major acetate synthesis
      pathways reduced acetate accumulation. The ackA-pta mutant strain also exhibits
      an increased lactate synthesis rate. Metabolic flux analysis suggested that the
      majority of excessive carbon flux was redirected through the lactate formation
      pathway rather than the ethanol synthesis pathway. This result indicated that
      lactate dehydrogenase may be competitive at the pyruvate node. However, a 10-fold
      overexpression of the fermentative lactate dehydrogenase (ldhA) gene in the wild
      type parent GJT001 was not able to divert carbon flux from acetate. The carbon
      flux through pyruvate and all its end products increases at the expense of flux
      through biosynthesis and succinate. Intracellular pyruvate measurements showed
      that strains overexpressing lactate dehydrogenase (LDH) depleted the pyruvate
      pool. This observation along with the observed excretion of pyruvate in the ackA
      pta strain indicates the significance of intracellular pyruvate pools. In the
      current study, we focus on the role of the intracellular pyruvate pool in the
      redirection of metabolic fluxes at this important node. An increasing level of
      extracellular pyruvate leads to an increase in the intracellular pyruvate pool.
      This increase in intracellular pyruvate affects carbon flux distribution at the
      pyruvate node. Partitioning of the carbon flux to acetate at the expense of
      ethanol occurs at the acetyl-CoA node while partitioning at the pyruvate node
      favors lactate formation. The increased competitiveness of the lactate pathway
      may be due to the allosteric activation of LDH as a result of increased pyruvate
      levels. The interaction between the reactions catalyzed by the enzymes PFL
      (pyruvate formate lyase) and LDH was examined.

PMID- 11289789
TI  - A MILP-based flux alternative generation and NMR experimental design strategy for
      metabolic engineering.
AB  - A mixed-integer linear program (MILP) is described that can enumerate all the
      ways fluxes can distribute in a metabolic network while still satisfying the same
      constraints and objective function. The multiple solutions can be used to (1)
      generate alternative flux scenarios that can account for limited experimental
      observations, (2) forecast the potential responses to mutation (e.g., new
      reaction pathways may be used), and (3) (as illustrated) design (13)C NMR
      experiments such that different potential flux patterns in a mutant can be
      distinguished. The experimental design is enabled by using the MILP results as an
      input to an isotopomer mapping matrices (IMM)-based program, which accounts for
      the network circulation of (13)C from a precursor such as glucose. The IMM-based
      program can interface to common plotting programs with the result that the user
      is provided with predicted NMR spectra that are complete with splittings and
      Lorentzian line-shape features. The example considered is the trafficking of
      carbon in an Escherichia coli mutant, which has pyruvate kinase activity deleted
      for the purpose of eliminating acetate production. Similar yields and
      extracellular measurements would be manifested by the flux alternatives. The MILP
      IMM results suggest how NMR experiments can be designed such that the spectra of
      glutamate for two flux distribution scenarios differ significantly.

PMID- 11289790
TI  - The organization of metabolic reaction networks. II. Signal processing in
      hierarchical structured functional units.
AB  - Based on the analysis of molecular interactions of proteins with DNA binding
      sites, a new approach to developing mathematical models describing gene
      expression is introduced. Detection of hierarchical structures in metabolic
      networks can be used to decompose complex reaction schemes. This will be achieved
      by assigning each regulator protein to one level in the hierarchy. Signals are
      then transduced from the top level to the lower level, but not vice versa. The
      method is shown by a simple example with two interacting proteins. A comparison
      of simulation results shows good agreement between a model taking all
      interactions into account and a model developed with the new approach. Finally,
      the method is applied to the crpA modulon in Escherichia coli, which controls
      uptake and metabolism for a number of carbohydrates. Here, RNA polymerase
      represents the top level, CrpA the second level, and the lactose-specific
      repressor LacI the lowest level, respectively. Besides the lactose operon, the
      method is applied to the adenylate cyclase gene and the gene for the regulator
      CrpA.

PMID- 11289791
TI  - Possible pitfalls of flux calculations based on (13)C-labeling.
AB  - Metabolic engineers have enthusiastically adopted the (13)C-labeling technique as
      a powerful tool for elucidating fluxes in metabolic networks. This tracer
      technique makes it possible to determine fluxes that are unobservable using only
      metabolite balances and allows the elimination of doubtful cofactor balances that
      are indispensable in flux analysis based on metabolite balancing alone. The (13)C
      labeling technique, however, relies on a number of assumptions that are not free
      from uncertainties. Two possible errors in the models that are needed to
      determine the metabolic fluxes from labeling data are omitted reactions and
      ignored occurrence of channeling. By means of two representative examples it is
      shown that these modeling errors may lead to serious errors in the calculated
      flux distributions despite the use of labeling data. A complicating fact is that
      the model errors are not always easily detected as poor models may still yield
      good fits of experimental data. Results of (13)C-labeling experiments should
      therefore be interpreted with appropriate caution.

PMID- 11289792
TI  - Signal transduction dynamics of the protein kinase-A/phosphofructokinase-2 system
      in Saccharomyces cerevisiae.
AB  - This work focuses on the phosphofructokinase-2-system dynamics in Saccharomyces
      cerevisiae, in vivo. The investigations were dedicated to the development and
      implementation of appropriate theoretical and experimental methods toward
      evaluation of a quantitative strategy for the characterization of systemic
      mechanisms involved in the cAMP/protein kinase-A/phosphofructokinase-2 signal
      transduction cascade in yeast. Upon glucose pulse experiments, applied to glucose
      limited continuous cultures of S. cerevisiae, the system response was determined
      with respect to alterations of intracellular metabolite concentrations or in vivo
      enzyme activities. Phosphofructokinase-2, in vivo, was found to be saturated with
      respect to both its substrates, F6P and ATP. This restriction results in an
      uncoupling of the enzyme activity and the signal transduction cascade from
      glycolytic flux, concluding that activation of phosphofructokinase-2 is
      exclusively a result of phosphorylation by protein kinase-A, which in turn is
      activated by increasing intracellular cAMP concentration after an extracellular
      glucose pulse. Signal processing from cAMP versus phosphofructokinase-2 also
      displays peculiar features implicated in a hysteresis behavior: when increasing
      cAMP concentration achieves a certain critical value, protein kinase-A switches
      into an active state. Posterior to this activation, the signal transform
      maintains autonomy and functional independence of further alterations of the
      intracellular cAMP concentration. Our observations, finally, allow the
      establishment of a representative model for the description of the signal
      transduction process via protein kinase-A in yeast.

PMID- 11289793
TI  - Modeling and experimental design for metabolic flux analysis of lysine-producing
      Corynebacteria by mass spectrometry.
AB  - Experimental design of (13)C-tracer studies for metabolic flux analysis with mass
      spectrometric determination of labeling patterns was performed for the central
      metabolism of Corynebacterium glutamicum comprising various flux scenarios. Ratio
      measurement of mass isotopomer pools of Corynebacterium products lysine, alanine,
      and trehalose is sufficient to quantify the flux partitioning ratios (i) between
      glycolysis and pentose phosphate pathways (Phi(PPP)), (ii) between the split
      pathways in the lysine biosynthesis (Phi(DH)), (iii) at the pyruvate node
      (Phi(PC)), and reversibilities of (iv) glucose 6-phosphate isomerase (zeta(PGI)),
      (v) at the pyruvate node (zeta(PC/PEPCK)), and (vi) of transaldolase and
      transketolases in the PPP. Weighted sensitivities for flux parameters were
      derived from partial derivatives to quantitatively evaluate experimental
      approaches and predict precision for estimated flux parameters. Deviation of
      intensity ratios from ideal values of 1 was used as weighting function. Weighted
      flux sensitivities can be used to identify optimal type and degree of tracer
      labeling or potential intensity ratios to be measured. Experimental design for
      lysine-producing strain C. glutamicum MH 20-22B (Marx et al., Biotechnol. Bioeng.
      49, 111-129, 1996) and various potential mutants with different alterations in
      the flux pattern showed that specific tracer labelings are optimal to quantify a
      certain flux parameter uninfluenced by the overall flux situation. Identified
      substrates of choice are [1-(13)C]glucose for the estimation of Phi(PPP) and
      zeta(PGI) and a 1 : 1 mixture of [U-(12)C/U-(13)C]glucose for the determination
      of zeta(PC/PEPCK). Phi(PC) can be quantified by feeding [4-(13)C]glucose or [U
      (12)C/U-(13)C]glucose (1 : 1), whereas Phi(DH) is accessible via [4
      (13)C]glucose. The sensitivity for the quantification of a certain flux parameter
      can be influenced by superposition through other flux parameters in the network,
      but substrate and measured mass isotopomers of choice remain the same. In special
      cases, reduced labeling degree of the tracer substrate can increase the precision
      of flux analysis. Enhanced precision and flux information can be achieved via
      multiply labeled substrates. The presented approach can be applied for effective
      experimental design of (13)C tracer studies for metabolic flux analysis.
      Intensity ratios of other products such as glutamate, valine, phenylalanine, and
      riboflavin also sensitively reflect flux parameters, which underlines the great
      potential of mass spectrometry for flux analysis.

PMID- 11289794
TI  - Viral immune evasion strategies and the underlying cell biology.
AB  - Evasion of the immune system by viruses is a well-studied field. It remains a
      challenge to understand how these viral tactics affect pathogenesis and the viral
      lifecycle. At the same time, the study of viral proteins involved in immune
      evasion has helped us to better understand a number of cellular processes at the
      molecular level. Here we review recent data on different viral tactics for immune
      evasion and highlight what these viral interventions might teach us about cell
      biology.

PMID- 11289796
TI  - Evasion of cytotoxic T lymphocytes by murine cytomegalovirus.
AB  - Murine cytomegalovirus causes lifelong infections with little pathology in normal
      host animals. Control of viral replication and prevention of pathology depend on
      both innate and adaptive immune mechanisms, and cytolytic T lymphocytes play a
      key role in this process. The virus encodes a number of genes which alter the
      normal assembly of class I major histocompatability complex proteins, and thus
      interfere with the ability of infected cells to present antigen to CD8(+)T cells.
      This review will examine what is known about these viral genes, and present some
      unanswered questions regarding the role of CTL evasion in the viral infectious
      cycle.

PMID- 11289795
TI  - Cytomegalovirus and transcriptional down-regulation of major histocompatibility
      complex class II expression.
AB  - CD4(+)T lymphocytes are a significant component of the afferent and efferent arms
      of adaptive immunity and are critical for controlling viral infections. CD4(+)T
      lymphocytes secrete cytokines that augment CD8(+)T lymphocyte and B lymphocyte
      responses and directly inhibit viral replication. The interface between the
      CD4(+)T lymphocyte and virus is the major histocompatibility complex (MHC) class
      II molecule. Cytomegalovirus, a beta-herpesvirus, has evolved mechanisms for
      inhibiting MHC class II expression and thus escaping CD4(+)T lymphocyte
      immunosurveillance. Herein, we review cytomegalovirus-mediated down-regulation of
      inducible and constitutive MHC class II expression, while focusing on lesions
      that occur at the level of MHC class II transcription.

PMID- 11289797
TI  - Immune evasion as a pathogenic mechanism of varicella zoster virus.
AB  - Varicella zoster virus (VZV) is a human herpesvirus that causes varicella
      (chickenpox) during primary infection, establishes latency in dorsal root ganglia
      and may reactivate years later, producing herpes zoster. VZV must evade antiviral
      immunity during three important stages of viral pathogenesis, including the cell
      associated viremia characteristic of primary infection, persistence in dorsal
      root ganglia during latency and the initial period of VZV reactivation. Our
      observations about the immunomodulatory effects of VZV document its capacity to
      interfere with adaptive immunity mediated by CD4 as well as CD8 T cells, ensuring
      the survival of the virus in the human population from generation to generation.

PMID- 11289798
TI  - Immune evasion by human cytomegalovirus: lessons in immunology and cell biology.
AB  - The human cytomegalovirus (HCMV) has dedicated a significant part of its genome
      to genes encoding molecules that modulate the host immune response. Many of these
      genes have homologues in the host genome. Others, however, are unique in the
      sense that no obvious primary sequence identity is found in the available
      databases. The HCMV gene products interfere with the activation of MHC class I
      and class II restricted T cells and NK cells, modify the function of cytokines
      and their receptors, interact with complement factors and modulate signal
      transduction and transcription factor activity, in addition to interference with
      many other cellular functions. Investigation of these evasion strategies has not
      only improved our understanding of HCMV pathogenesis, but has also provided
      unexpected, novel insights into basic cell biological and immunological
      processes.

PMID- 11289799
TI  - Living in oblivion: HIV immune evasion.
AB  - The human and simian immunodeficiency viruses (HIV and SIV, respectively) are
      members of the lentiviridae subgroup of retroviruses that cause a progressive
      failure of the host immunological functions culminating in the clinical collapse
      known as AIDS, or acquired immunodeficiency syndrome. In the absence of antiviral
      therapy, this course is inexorable in spite of an initially vigorous immune
      response. Two fundamental characteristics of the biology of primate lentiviruses
      explain this apparent paradox. First, HIV and SIV infect CD4(+)targets such as
      helper T lymphocytes and macrophages, that is, cells that normally play an
      essential role in the emergence and maintenance of an effective antiviral
      response. Second, these viruses have evolved a number of strategies to evade
      control by the immune system. These include mutational escape, latency, masking
      of antibody-binding sites on the viral envelope, downmodulation of the class I
      major histocompatibility complex (MHC-I), and upregulation of the Fas ligand on
      the surface of infected cells. Examining the mechanisms of these phenomena not
      only helps to understand how HIV wins its war against the immune system, but it
      also suggests as yet unexploited avenues to combat the virus through therapies
      and to develop a vaccine.

PMID- 11289800
TI  - Immunology 101 at poxvirus U: immune evasion genes.
AB  - Poxviruses, unlike some other large DNA viruses, do not undergo a latent stage
      but rely on the expression of viral proteins to evade host immune responses. Of
      the many poxviral evasion genes identified, most target cytokines or other innate
      immune defenses. Resistance to interferons appears to be a priority as there are
      viral proteins that prevent their induction, receptor binding, and action.
      Additional poxviral proteins inhibit complement activation, chemokines, IL-1 beta
      and tumor necrosis factor. The identification of viral immune evasion genes and
      the determination of their roles in virus survival and spread contribute to our
      understanding of immunology and microbiology.

PMID- 11289801
TI  - Immunology 102 at poxvirus U: avoiding apoptosis.
AB  - Poxviruses are large complex viruses that replicate in the cytoplasm of cells
      without integrating their DNA into the host genome or undergoing a latent
      intracellular stage. In addition to viral enzymes for DNA and RNA synthesis,
      poxviruses encode many proteins that modulate host responses. These include
      inhibitors of apoptosis induced by ligand binding to cell surface receptors,
      peroxides, ultraviolet light, DNA damaging agents and other cell signaling
      pathways.

PMID- 11289802
TI  - Immunomodulatory proteins of myxoma virus.
AB  - Poxviruses collectively encode an impressive collection of diverse
      immunomodulatory proteins. In this review we draw attention to some of the new
      open reading frames (ORFs) discovered during the sequencing of the myxoma virus
      DNA genome [Cameron C, Hota-Mitchell S, Chen L, Barrett J, Cao J-X, Macaulay C,
      Willer D, Evans D, McFadden G (1999) The complete DNA sequence of myxoma virus.
      Virology 264:298-318] that may function to subvert the host immune system. Most
      of these predicted functions are speculative but some of the deduced primary
      amino acid sequences contain intriguing similarities to known cellular and viral
      proteins in the public domain for which immunomodulatory functions have been
      assigned.

PMID- 11289803
TI  - Nuclear export of influenza virus ribonucleoproteins: identification of an export
      intermediate at the nuclear periphery.
AB  - A critical phase of the influenza virus life cycle is the regulated translocation
      of genomic ribonucleoproteins (vRNPs) from the nuclear interior, across the
      nuclear envelope, and into the cytoplasm. Two viral proteins, M1 and NS2, have
      previously been implicated as mediators of vRNP export. We show here that vRNP
      nuclear export is prevented by leptomycin B (LMB), an inhibitor of the cellular
      factor CRM1. In LMB-treated cells, vRNPs were found in a peripheral nuclear
      location that localized with the nuclear lamina. vRNPs were not colocalized with
      either M1 or NS2. In situ extraction of cells late in infection also revealed a
      peripheral localization of nuclear vRNPs, whereas early in infection vRNPs were
      dispersed throughout the nuclear interior. We believe that vRNPs at the nuclear
      periphery represent a novel intermediate in the influenza virus nuclear export
      pathway.

PMID- 11289804
TI  - Features of the 3'-consensus sequence of rotavirus mRNAs critical to minus strand
      synthesis.
AB  - The last seven nucleotides of the 3'-end of rotavirus mRNAs, 5'-UGUGACC-3', are
      highly conserved and form a cis-acting signal that can promote the synthesis of (
      ) strand RNA to produce the viral dsRNA genome in vitro. Previous studies have
      shown that the sequence, location, and strandedness (single- versus double
      stranded) of the 3'-consensus sequence of the mRNA affect the efficiency of (-)
      strand synthesis. In this study, we have used exhaustive mutagenesis of the SA11
      gene 8 mRNA and an in vitro replication system to define the importance of each
      of the residues in the consensus sequence in (-) strand synthesis. The analysis
      showed that the CC of the consensus sequence was the most critical for (-) strand
      synthesis. Furthermore, the data revealed that other, but not all, residues of
      the consensus sequence contributed to efficient (-) strand synthesis in vitro.
      Mutant gene 8 RNAs supported an intermediate level of (-) strand synthesis when
      the 15 nt sequence upstream of the CC was replaced with long tracts of poly(A) or
      poly(U), but not with poly(G). Predictions of the secondary structure of the
      mutant RNAs suggested that the poly(G)-RNA could not replicate because its 3'
      terminus was largely basepaired, instead of extending as a single-stranded tail
      as is the case for the 3'-termini of the poly(A)- and poly(U)-RNAs and wild-type
      gene 8 RNA. Subsequent experiments performed with complementary oligonucleotides
      indicated that efficient RNA replication occurs in vitro only when the last four
      residues of the 3'-consensus sequence, and most importantly the two terminal C's,
      existed in a single-stranded form. A single-stranded CC may be crucial for
      formation of an initiation complex for (-) strand synthesis consisting of viral
      RdRP, mRNA, and the dinucleotide pGpG.

PMID- 11289805
TI  - Three distinct mechanisms facilitate genetic isolation of sympatric wheat streak
      mosaic virus lineages.
AB  - Cross-protection and vector transmission bottlenecks have been proposed as
      mechanisms facilitating genetic isolation of sympatric viral lineages. Molecular
      markers were used to monitor establishment and resolution of mixed infections
      with genetically defined strains of wheat streak mosaic virus (WSMV). Two closely
      related WSMV strains from the U.S. (Type and Sidney 81) exhibited reciprocal
      cross-protection in wheat, confirming this classic phenomenon as a mechanism of
      genetic isolation. In contrast, cross-protection between either U.S. strain and
      the divergent El Batan 3 strain from Mexico was unilateral, erratic, and only
      partially effective. Distribution of WSMV strains within individual leaves of
      plants supporting a mixed infection of Type and Sidney 81 was spatially
      nonuniform. Strain distribution among individual tillers of coinfected plants
      also was heterogeneous, with some containing either Type or Sidney 81 alone and
      some containing both. Transmission by wheat curl mites, acquiring virus from
      source plants simultaneously infected with both Type and Sidney 81, often
      resulted in test plants bearing only a single WSMV strain. Spatial subdivision of
      virus strains within coinfected plants likely contributed to vector transmission
      bottlenecks during acquisition. Collectively, these three distinct mechanisms
      enhance genetic isolation of individual viral lineages, and together with
      stochastic processes, may explain generation and maintenance of genetic diversity
      in field populations.

PMID- 11289806
TI  - Association of bovine papillomavirus type 1 with microtubules.
AB  - Transport of BPV-1 virus from the cell membrane to the nucleus was studied in
      vitro in CV-1 cells. At reduced temperature (4 degrees C), BPV-1 binding to CV-1
      cells was unaffected but there was no transport of virions across the cytosol.
      Electron microscopy showed BPV-1 virions in association with microtubules in the
      cytoplasm, a finding confirmed by co-immunoprecipitation of L1 protein and
      tubulin. Internalization of virus was unimpaired in cells treated with the
      microtubule-depolymerizing drug nocodazole but virions were retained in
      cytoplasmic vesicles and not transported to the nucleus. We conclude that a
      microtubule transport mechanism in CV-1 cells moves intact BPV-1 virions from the
      cell surface to the nuclear membrane.

PMID- 11289807
TI  - Human herpesvirus 8 interaction with target cells involves heparan sulfate.
AB  - Human herpesvirus 8 (HHV-8) or Kaposi's sarcoma associated herpesvirus (KSHV) is
      associated with Kaposi's sarcoma and primary effusion lymphoma. In vivo, HHV-8
      DNA and transcripts have been detected in B cells, endothelial cells,
      macrophages, and epithelial cells. HHV-8 infects a variety of cell lines of human
      and animal origin, leading to latent or abortive infection. This study shows that
      the broad cellular tropism of HHV-8 may be in part due to its interaction with
      the ubiquitous host cell surface molecule, heparan sulfate (HS). This conclusion
      is based on the following findings: (i) HHV-8 infection of human foreskin
      fibroblast (HFF) cells was inhibited in a dose-dependent manner by soluble
      heparin, a glycosaminoglycan closely related to HS. Chondroitin sulfates A and C
      did not inhibit HHV-8 infection. (ii) Enzymatic removal of HFF cell surface HS
      with heparinase I and III reduced HHV-8 infection. (iii) Soluble heparin
      inhibited the binding of radiolabeled HHV-8 to human B cell lines, embryonic
      kidney epithelial (293) cells, and HFF cells, suggesting interference at the
      virus attachment stage. (iv) Cell surface adsorbed HHV-8 was displaced by soluble
      heparin. (v) Radiolabeled HHV-8 also bound to wild-type HS expressing Chinese
      hamster ovary (CHO-K1) cells. In contrast, binding of virus to mutant CHO cells
      deficient in HS was significantly reduced. These data show that the gamma2
      herpesvirus HHV-8, similar to some members of alpha, beta, and gamma2
      herpesviruses, adsorbs to cells by binding to cell surface HS-like moieties.
      Heparin did not completely prevent the binding and infectivity of HHV-8,
      suggesting that HHV-8 interactions with HS could be the first set of ligand
      receptor interaction leading to the binding with one or more host cell receptors
      essential for the subsequent viral entry process.

PMID- 11289808
TI  - Comparison of murine and human nectin1 binding to herpes simplex virus
      glycoprotein D (gD) reveals a weak interaction of murine nectin1 to gD and a gD
      dependent pathway of entry.
AB  - The murine nectin1alpha (mNectin1alpha), a homolog of human nectin1alpha
      (hNectin1alpha, or PRR1, HveC), mediates the entry of herpes simplex virus (HSV)
      into cells. Previously, we reported that the binding of hNectin1 to HSV
      glycoprotein D (gD) was readily detectable, whereas the binding of mNectin1 to gD
      was not detectable, thus raising the question whether mNectin1 mediates a gD
      dependent or a gD-independent pathway of entry. Here we report comparative
      binding studies of murine- and human-nectin1alpha to virions and to gD. The
      assays consistently showed either a very weak binding or no detectable binding of
      murine nectin1alpha to gD. They included (i) binding of soluble mNectin1-Fc or
      hNectin1-Fc to virions and competition of the binding by soluble gD(Delta290
      299t) and by monoclonal antibodies to gD; (ii) pull-down experiments of wt gD
      from lysates of infected cells; and (iii) ELISA binding of soluble gD(Delta290
      299t) to cells expressing mNectin1 or hNectin1. In contrast to the binding
      studies, the entry studies readily showed that entry mediated by mNectin1 was
      dependent on gD. Thus, a gDnull (gD-/-) mutant virus was unable to enter mNectin1
      expressing cells, and entry of wild-type virus was inhibited by antibodies to gD
      or soluble gD at similar concentrations. We infer that gD represents a weak
      ligand in the interaction between mNectin1 and virions, whereas it represents a
      strong and the major ligand for hNectin1. Yet gD is required in HSV-1 entry
      mediated by mNectin1alpha. We conclude that a high-affinity binding of the
      receptor to gD is not a requirement in the gD-dependent pathway of HSV entry to
      cells.

PMID- 11289809
TI  - HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI
      3-kinase-dependent pathway.
AB  - HIV causes a chronic infection by evading immune eradication. A key element of
      HIV immune escape is the HIV-1 Nef protein. Nef causes a reduction in the level
      of cell surface major histocompatibility complex class I (MHC-I) protein
      expression, thus protecting HIV-infected cells from anti-HIV cytotoxic T
      lymphocyte (CTL) recognition and killing. Nef also reduces cell surface levels of
      the HIV receptor, CD4, by accelerating endocytosis. We show here that endocytosis
      is not required for Nef-mediated downmodulation of MHC-I molecules. The main
      effect of Nef is to block transport of MHC-I molecules to the cell surface,
      leading to accumulation in intracellular organelles. Furthermore, the effect of
      Nef on MHC-I molecules (but not on CD4) requires phosphoinositide 3-kinase (PI 3
      kinase) activity. We propose that Nef diverts MHC-1 proteins into a PI 3-kinase
      dependent transport pathway that prevents expression on the cell surface.

PMID- 11289810
TI  - The transmembrane domains of the EBV-encoded latent membrane protein 1 (LMP1)
      variant CAO regulate enhanced signalling activity.
AB  - Sequence variants of the Epstein-Barr virus (EBV)-encoded latent membrane protein
      1 (LMP1) have been reported in association with EBV-linked malignancies but
      little is known about their effects on signalling pathways and phenotype. We have
      examined the ability of the nasopharyngeal carcinoma (NPC)-derived variant, CAO
      LMP1 to activate the transcription factors NF-kappaB and AP-1 in epithelial
      cells. In this study, transient expression of CAO-LMP1 was found to activate
      higher levels of NF-kappaB and AP-1 than the prototype B95.8-LMP1 in human
      embryonic kidney (HEK) 293 cells and SV40-transformed keratinocytes (SVK). In
      addition, pulse-chase analysis revealed that CAO-LMP1 has a longer half-life than
      B95.8-LMP1. Chimera studies localised these phenomena to the transmembrane
      domains of CAO-LMP1, suggesting that this enhanced signalling capacity may be a
      consequence of its prolonged half-life. The ability of CAO-LMP1 to activate
      higher levels of NF-kappaB and AP-1 may contribute to its potent transforming
      properties.

PMID- 11289811
TI  - Infectious cDNA clone of attenuated Langat tick-borne flavivirus (strain E5) and
      a 3' deletion mutant constructed from it exhibit decreased neuroinvasiveness in
      immunodeficient mice.
AB  - Forty-five years ago a naturally attenuated tick-borne flavivirus, Langat (LGT)
      strain TP21, was recovered from ticks in Malaysia. Subsequently, it was tested as
      a live attenuated vaccine for virulent tick-borne encephalitis viruses. In a
      large clinical trial its attenuation was confirmed but there was evidence of a
      low level of residual virulence. Thirty-five years ago further attenuation of LGT
      TP21 was achieved by multiple passages in eggs to yield mutant E5. To study the
      genetic determinants of the further attenuation exhibited by E5 and to allow us
      to manipulate the genome of this virus for the purpose of developing a
      satisfactory live attenuated tick-borne flavivirus vaccine, we recovered
      infectious E5 virus from a full-length cDNA clone. The recombinant E5 virus
      (clone 651) recovered from a full-length infectious cDNA clone was more
      attenuated in immunodeficient mice than that of its biologically derived E5
      parent. Increase in attenuation was associated with three amino acid
      substitutions, two located in the structural protein E and one in nonstructural
      protein NS4B. Subsequently an even greater degree of attenuation was achieved by
      creating a viable 320 nucleotide deletion in the 3'-noncoding region of
      infectious full-length E5 cDNA. This deletion mutant was not cytopathic in simian
      Vero cells and it replicated to lower titer than its E5-651 parent. In addition,
      the E5 3' deletion mutant was less neuroinvasive in SCID mice than its E5-651
      parent. Significantly, the deletion mutant proved to be 119,750 times less
      neuroinvasive in SCID mice than its progenitor, LGT strain TP21. Despite its high
      level of attenuation, the E5 3' deletion mutant remained highly immunogenic and
      intraperitoneal (ip) inoculation of 10 PFU induced complete protection in Swiss
      mice against subsequent challenge with 2000 ip LD50 of the wild-type LGT TP21.

PMID- 11289812
TI  - Antigenic and genetic characterization of swine influenza A (H1N1) viruses
      isolated from pneumonia patients in The Netherlands.
AB  - It is generally believed that pigs can serve as an intermediate host for the
      transmission of avian influenza viruses to humans or as mixing vessels for the
      generation of avian-human reassortant viruses. Here we describe the antigenic and
      genetic characterization of two influenza A (H1N1) viruses, which were isolated
      in The Netherlands from two patients who suffered from pneumonia. Both viruses
      proved to be antigenically and genetically similar to avian-like swine influenza
      A (H1N1) viruses which currently circulate in European pigs. It is concluded that
      European swine H1N1 viruses can infect humans directly, causing serious disease
      without the need for any reassortment event.

PMID- 11289813
TI  - Rubella virus RNA replication is cis-preferential and synthesis of negative- and
      positive-strand RNAs is regulated by the processing of nonstructural protein.
AB  - Rubella virus (RV) genome encodes nonstructural protein (NSP) in a large open
      reading frame at its 5' end. It is translated into p200 and further processed
      into p150 and p90. The NSPs are responsible for viral RNA replication, during
      which a full-length negative-strand RNA serves as the intermediate for the
      replication of positive-strand genomic RNA and the transcription of subgenomic
      RNA. Using complementation experiments, we demonstrated that RV negative-strand
      RNA is synthesized preferentially in cis while positive-strand RNAs can be
      synthesized both in cis and in trans but with higher efficiency in cis. During
      virus infection, negative-strand RNA accumulates until 10 hours postinfection
      (hpi) and remains nearly constant thereafter. In contrast, positive-strand RNAs
      (both genomic and subgenomic RNA) do not increase much before 10 hpi and
      accumulate rapidly thereafter. Previously we demonstrated that p200 synthesizes
      negative- but not positive-strand RNA, whereas cleavage products p150/p90 are
      required for efficient production of positive-strand RNAs. In this study, we
      present evidence demonstrating that a higher concentration of p150/p90 is
      associated with lower production of negative-strand RNA. Our data support the
      hypothesis that p200 is the principal replicase for negative-strand RNA, as is
      p150/p90 for positive-strand RNA. The switch from the synthesis of negative- to
      positive-strand RNA is thus regulated by NSP processing, which not only activates
      the efficient production of positive-strand RNA, but also disables negative
      strand RNA synthesis. A mechanism for NSP translation, processing, and regulation
      of RV RNA synthesis is proposed.

PMID- 11289814
TI  - Identification and functional analysis of an interaction between domains of the
      126/183-kDa replicase-associated proteins of tobacco mosaic virus.
AB  - The Tobacco mosaic virus (TMV) 126-kDa and read-through 183-kDa replicase
      associated proteins have been shown to interact [Watanabe, T., Honda, A., Iwata,
      A., Ueda, S., Hibi, T., Ishihama, A. (1999). J. Virol. 73, 2633-2640]. To
      identify and investigate the sequence required for this interaction, five
      segments covering different portions of the 126/183-kDa open reading frame,
      including the methyl-transferase, intervening region (IR), helicase-like (HEL),
      and polymerase domains, were screened via the yeast two-hybrid system against a
      library of TMV protein segments. Only one specific interaction between the HEL
      domain clone and a TMV library clone, IRnHEL, encoding the C-terminal half of the
      IR and the N-terminal portion of the HEL domain was identified. Sequence and
      deletion analysis revealed that the interacting clones share a region containing
      the helicase NTP-binding motif and that this region was essential for the
      interaction. To determine the functional significance of this interaction,
      mutants of the HEL domain segment that conferred a temperature-sensitive (ts)
      defect in the yeast interaction were identified and cloned into a recombinant TMV
      strain. Of the five selected mutants, three (V823I/S824N/V1042M, A877V, V1087I)
      produced a ts replication phenotype in protoplasts while the other two (A1073V,
      T884I) abolished TMV replication at both the permissive and the nonpermissive
      temperatures. An additional mutation, K839S, designed to disrupt the shared NTP
      binding motif, nearly abolished the two-hybrid interaction and prevented virus
      replication, suggesting that NTP-binding and/or the structure of this motif is a
      contributing factor in the interaction. Taken together, these results provide
      support for an interaction between TMV replicase-associated proteins that
      involves specific structural features of the HEL and IR domains.

PMID- 11289815
TI  - Functional evaluation of HIV/SIV Nef as superantigen.
AB  - It is speculated that a virus-encoded superantigen is involved in the
      pathogenesis of human and simian immunodeficiency virus infections and that the
      accessory protein Nef might be that superantigen. We are able to show, using a
      murine superantigen screening system, that Nef does not display features
      characteristic of a superantigen. Upon transfection into MHC class II expressing
      antigen-presenting cells, it is expressed, but fails to induce Vbeta-specific
      expansion of peripheral T lymphocytes, which is a characteristic feature of
      superantigens in mixed lymphocyte culture. Therefore, we cannot support the
      hypothesis that Nef is a superantigen. The observations in favor of that
      hypothesis must be explained by other mechanisms.

PMID- 11289816
TI  - Molecular characterization of the genome of Maize rayado fino virus, the type
      member of the genus Marafivirus.
AB  - The complete nucleotide sequence of the single-stranded RNA genome of Maize
      rayado fino virus (MRFV), the type member of the genus Marafivirus, is 6305
      nucleotides (nts) in length and contains two putative open reading frames (ORFs).
      The largest ORF (nt 97-6180) encodes a polyprotein of 224 kDa with sequence
      similarities at its N-terminus to the replication-associated proteins of other
      viruses with positive-strand RNA genomes and to the papainlike protease domain
      found in tymoviruses. The C-terminus of the 224-kDa ORF also encodes the MRFV
      capsid protein. A smaller, overlapping ORF (nt 302-1561) encodes a putative
      protein of 43 kDa with unknown function but with limited sequence similarities to
      putative movement proteins of tymoviruses. The nucleotide sequence and proposed
      genome expression strategy of MRFV is most closely related to that of oat blue
      dwarf virus (OBDV). Unlike OBDV, MRFV RNA does not appear to contain a poly(A)
      tail, and it encodes a putative second overlapping open reading frame.

PMID- 11289818
TI  - Bell's theorem without inequalities and without probabilities for two observers.
AB  - A proof of Bell's theorem using two maximally entangled states of two qubits is
      presented. It exhibits a similar logical structure to Hardy's argument of
      "nonlocality without inequalities." However, it works for 100% of the runs of a
      certain experiment. Therefore, it can also be viewed as a Greenberger-Horne
      Zeilinger-like proof involving only two spacelike separated regions.

PMID- 11289819
TI  - Formation of pairing fields in resonantly coupled atomic and molecular bose
      einstein condensates.
AB  - We show that pair correlations may play an important role in the dynamical
      properties of a Bose-Einstein condensed gas composed of an atomic field
      resonantly coupled with a condensed field of molecular dimers. Specifically, pair
      correlations in this system can dramatically modify the coherent and incoherent
      transfers between the atomic and molecular fields.

PMID- 11289820
TI  - Search for exchange-antisymmetric states for spin-0 particles at the 10(-11)
      level.
AB  - We set a new upper limit of 1.7x10(-11) to the probability that two spin-0 16O
      nuclei are in forbidden exchange-antisymmetric states, testing the validity of
      fundamental principles of quantum mechanics. A newly designed difference
      frequency spectrometer is used to look for the existence of these states. The
      experimental test was performed by tuning the spectrometer across a molecular
      transition of 12C 16O (2) belonging to the rovibrational band at 4.25 microm,
      connecting the forbidden states (00(0)0,J = 25) and (00(0)1,J = 26).

PMID- 11289821
TI  - Noise- and force-induced resonances in noisy rotary oscillations of classical
      spins.
AB  - As an important example of noisy rotary oscillations, the dynamic magnetization
      of an assembly of superparamagnetic particles is considered. In the presence of a
      bias field, there exists a mechanism that causes selective suppression of higher
      harmonics in the response spectrum of the system. Manifestation of this effect at
      temperature variation is known as the noise-induced resonance. Its manifestation
      at the change of excitation intensity, formerly unknown, we term the force
      induced resonance.

PMID- 11289822
TI  - Quantum approach to a derivation of the second law of thermodynamics.
AB  - We reinterpret the microcanonical conditions in the quantum domain as constraints
      for the interaction of the "gas subsystem" under consideration and its
      environment ("container"). The time average of a purity measure is found to equal
      the average over the respective path in Hilbert space. We then show that for
      typical (degenerate or nondegenerate) thermodynamical systems almost all states
      within the allowed region of Hilbert space have a local von Neumann entropy S
      close to the maximum and a purity P close to its minimum, respectively.
      Typically, thermodynamical systems should obey the second law.

PMID- 11289823
TI  - Radiation reaction and the self-force for a point mass in general relativity.
AB  - A point particle of mass mu moving on a geodesic creates a perturbation h(mu), of
      the spacetime metric g(0), that diverges at the particle. Simple expressions are
      given for the singular mu/r part of h(mu) and its quadrupole distortion caused by
      the spacetime. Subtracting these from h(mu) leaves a remainder h(R) that is C1.
      The self-force on the particle from its own gravitational field corrects the
      world line at O(mu) to be a geodesic of g(0)+h(R). For the case that the particle
      is a small nonrotating black hole, an approximate solution to the Einstein
      equations is given with error of O(mu(2)) as mu-->0.

PMID- 11289824
TI  - Simulation of the spherically symmetric stellar core collapse, bounce, and
      postbounce evolution of a star of 13 solar masses with boltzmann neutrino
      transport, and its implications for the supernova mechanism.
AB  - With exact three-flavor Boltzmann neutrino transport, we simulate the stellar
      core collapse, bounce, and postbounce evolution of a 13M star in spherical
      symmetry, the Newtonian limit, without invoking convection. In the absence of
      convection, prior spherically symmetric models, which implemented approximations
      to Boltzmann transport, failed to produce explosions. We consider exact transport
      to determine if these failures were due to the transport approximations made and
      to answer remaining fundamental questions in supernova theory. The model
      presented here is the first in a sequence of models beginning with different
      progenitors. In this model, a supernova explosion is not obtained.

PMID- 11289825
TI  - Opportunities for future supernova studies of cosmic acceleration.
AB  - We investigate the potential of a future supernova data set, as might be obtained
      by the proposed SNAP satellite, to discriminate among different "dark energy"
      theories that describe an accelerating Universe. We find that many such models
      can be distinguished with a fit to the effective pressure-to-density ratio w of
      this energy. More models can be distinguished when the effective slope dw/dz of a
      changing w is also fit, but only if our knowledge of the current mass density
      Omega(m) is improved. We investigate the use of "fitting functions" to interpret
      luminosity distance data from supernova searches.

PMID- 11289826
TI  - Deconfinement and the Hagedorn transition in string theory.
AB  - We introduce a new definition of the thermal partition function in string theory.
      With this new definition, the thermal partition functions of all of the string
      theories obey thermal duality relations with self-dual Hagedorn temperature
      beta(2)(H) = 4pi(2)alpha('). A beta-->beta(2)(H)/beta transformation maps the
      type I theory into a new string theory (type I) with thermal D p-branes, spatial
      hypersurfaces supporting a p-dimensional finite temperature non-Abelian Higgs
      gauge theory for p< or =9. We demonstrate a continuous phase transition in the
      behavior of the static heavy quark-antiquark potential for small separations
      r(2)(*)<<alpha(') transitioning through a precise inverse power law at a critical
      temperature T(D) = T(H)r(*)/(2alpha('))(1/2)pi.

PMID- 11289827
TI  - A convergent series for the QED effective action.
AB  - The one-loop effective action of QED obtained by Heisenberg and Euler and by
      Schwinger has been expressed by an asymptotic perturbative series which is
      divergent. In this Letter we present a nonperturbative but convergent series of
      the effective action. With the convergent series we establish the existence of
      the manifest electric-magnetic duality in the one-loop effective action of QED.

PMID- 11289828
TI  - Renormalization-group improved calculation of top-quark production near
      threshold.
AB  - The top-quark cross section close to threshold in e(+)e(-) annihilation is
      computed including the summation of logarithms of the velocity at next-to-next-to
      leading-logarithmic order in QCD. The remaining theoretical uncertainty in the
      normalization of the total cross section is at the few-percent level, an order of
      magnitude smaller than in previous next-to-next-to-leading order calculations.
      This uncertainty is smaller than the effects of a light standard-model Higgs
      boson.

PMID- 11289830
TI  - Criticality in quark-gluon systems far beyond thermal and chemical equilibrium.
AB  - Experimental evidence and theoretical arguments for the existence of self
      organized criticality in systems of gluons and quarks are presented. It is
      observed that the existing data for high-transverse-momentum jet production
      exhibit striking regularities; and it is shown that such regularities can be used
      not only to probe the possible compositeness of quarks but also to obtain direct
      evidence for, or against, the existence of critical temperature and/or critical
      chemical potential in quark-gluon systems when hadrons are squeezed together.

PMID- 11289833
TI  - Probing the nuclear equation of state by K+ production in heavy-ion collisions.
AB  - The dependence of K+ production on the nuclear equation of state is investigated
      in heavy-ion collisions. An increase of the excitation function of K+
      multiplicities obtained in heavy (Au+Au) over light (C+C) systems when going far
      below threshold which has been observed by the KaoS Collaboration strongly favors
      a soft equation of state. This observation holds despite the influence of an in
      medium kaon potential predicted by effective chiral models which is necessary to
      reproduce the experimental K+ yields.

PMID- 11289832
TI  - Baryon rapidity loss in relativistic Au + Au collisions.
AB  - An excitation function of proton rapidity distributions for different
      centralities is reported from AGS Experiment E917 for Au+Au collisions at 6, 8,
      and 10.8 GeV/nucleon. The rapidity distributions from peripheral collisions have
      a valley at midrapidity which smoothly change to distributions that display a
      broad peak at midrapidity for central collisions. The mean rapidity loss
      increases with increasing beam energy, whereas the fraction of protons consistent
      with isotropic emission from a stationary source at midrapidity decreases with
      increasing beam energy. The data suggest that the stopping is substantially less
      than complete at these energies.

PMID- 11289834
TI  - Limits on the existence of heavy neutrinos in the range 50-1000 eV from the study
      of the 187Re beta decay.
AB  - We analyzed the spectrum of the 187Re beta decay, obtained with a cryogenic
      microcalorimeter, searching for heavy neutrinos in the mass range 50-1000 eV. No
      evidence has been found for them and the upper limits on the mixing angle with a
      zero-mass neutrino are reported. Upper limits of 9x10(-3) at 1000 eV/c(2),
      1.2x10(-2) at 500 eV/c(2), 4.4x10(-2) at 200 eV/c(2), and 0.116 at 100 eV/c(2) at
      95% C.L. have been obtained. These upper limits are a factor of 2 to 4 lower than
      the current limits reported in the literature.

PMID- 11289831
TI  - Event-by-event fluctuations of the Kaon-to-Pion ratio in central Pb+Pb collisions
      at 158 GeV per nucleon.
AB  - We present the first measurement of fluctuations from event to event in the
      production of strange particles in collisions of heavy nuclei. The ratio of
      charged kaons to charged pions is determined for individual central Pb+Pb
      collisions. After accounting for the fluctuations due to detector resolution and
      finite number statistics we derive an upper limit on genuine nonstatistical
      fluctuations, which could be related to a first- or second-order QCD phase
      transition. Such fluctuations are shown to be very small.

PMID- 11289836
TI  - Reaction mechanisms for two-neutron halo breakup.
AB  - We describe a reaction mechanism which is consistent with all available
      experimental information of high energy three-body breakup processes. The
      dominating channels are removal of one of the three halo particles leaving the
      other two either undisturbed or absorbed. We compare with the commonly used
      deceptive assumption of a decay through two-body resonance states. Our
      predictions can be tested by measuring neutron-neutron invariant mass spectra.

PMID- 11289835
TI  - Measurement of the B(e2) of (7)(lambda)Li and shrinkage of the hypernuclear size.
AB  - We report on the first measurement of a hypernuclear gamma-transition
      probability. gamma rays emitted in the E2(5/2(+)-->1/2(+)) transition of
      (7)(Lambda)Li were detected by a large-acceptance germanium detector array
      (Hyperball), and the lifetime of the parent state ( 5/2(+)) was determined by the
      Doppler shift attenuation method. The obtained result, 5.8(+0.9)(-0.7)+/-0.7 ps,
      was then converted into the reduced transition probability [ B(E2)] to be
      B(E2;5/2(+)-->1/2(+)) = 3.6+/-0.5(+0.5)(-0.4) e(2) fm(4). Compared with the B(E2)
      of the corresponding E2(3(+)-->1(+)) transition in the 6Li nucleus, our result
      gives evidence that the size of the 6Li core in (7)(Lambda)Li is smaller than the
      6Li nucleus in the free space.

PMID- 11289837
TI  - Leading logarithmic contribution to the second-order lamb shift induced by the
      loop-after-loop diagram.
AB  - The contribution of order alpha(2)(Zalpha)(6)ln (3)(Zalpha)(-2) to the ground
      state Lamb shift in hydrogen induced by the loop-after-loop diagram is evaluated
      analytically. An additional contribution of this order is found compared to the
      previous calculation by Karshenboim [Sov. Phys. JETP 76, 541 (1993)]. As a
      result, agreement is achieved for this correction between different numerical and
      analytical methods.

PMID- 11289838
TI  - Structural properties of two-component coulomb crystals in linear paul traps.
AB  - We report on structural properties of two-component Coulomb crystals in a linear
      Paul trap. The crystals consist of two laser cooled ion species, 24Mg+ and 40Ca+.
      The lighter 24Mg+ ions form an inner cylindrical crystal structure surprisingly
      similar to that of an infinitely long single component crystal, while the
      outermost shell of the surrounding 40Ca+ ions have a spheroidal shape, which is
      highly insensitive to the presence of the 24Mg+ ions. Observed changes in the
      radial separation of the two ion species with the radius of the inner cylindrical
      crystal is explained by a simple model.

PMID- 11289839
TI  - Fine structure continuum cross section ratios in the two-photon ionization of
      rubidium using elliptically polarized light.
AB  - Using fully relativistic perturbation theory we report fine structure continuum
      cross section ratios for the two-photon ionization of rubidium under elliptically
      polarized light. The choice of light polarization and wavelength matches the
      recent complete experiments on rubidium reported by Wang and Elliott [Phys. Rev.
      Lett. 84, 3795 (2000)]. The sigma(d5/2)/sigma(d3/2) cross section ratios
      calculated are consistent with results expected if relativistic fine structure
      effects are small, and are very much at odds with the recent experimental
      findings.

PMID- 11289840
TI  - Doppler-free two-photon millimeter wave transitions in OCS and CHF3.
AB  - Doppler-free two-photon rotational transitions J = 13<--<--11 and J = 12<--<--10
      of OCS and J = 8<--<--6 and J = 7<--<--5 of CHF (3) were detected in the
      frequency range 134-156 GHz, using a novel, highly sensitive intracavity-jet
      technique. The sub-Doppler narrowing of the observed peaks (down to 40 kHz full
      width at half maximum as compared to 300 kHz of the Doppler width) demonstrates
      the potential of this new technique for high precision millimeter wave
      spectroscopy. The possibilities of the further reduction of the two-photon
      absorption line widths are considered.

PMID- 11289829
TI  - Ratios of multijet Cross Sections in p p collisions at radical(s) = 1.8 TeV.
AB  - We report on a study of the ratio of inclusive three-jet to inclusive two-jet
      production cross sections as a function of total transverse energy in p&pmacr;
      collisions at a center-of-mass energy sqrt[s] = 1.8 TeV, using data collected
      with the D0 detector during the 1992-1993 run of the Fermilab Tevatron Collider.
      The measurements are used to deduce preferred renormalization scales in
      perturbative O(alpha(3)(s)) QCD calculations in modeling soft-jet emission.

PMID- 11289841
TI  - Anomalous stimulated Brillouin scattering via ultraslow light.
AB  - We study stimulated Brillouin scattering (SBS) in an ultradispersive coherent
      medium, and show that the properties of SBS change drastically when the group
      velocity of light in the material approaches or becomes less than the speed of
      sound. In particular, forward SBS not allowed in a dispersionless bulk medium
      takes place in the coherent medium.

PMID- 11289842
TI  - Parametric three-wave soliton generated from incoherent light.
AB  - We show analytically and numerically that, under certain conditions, coherent
      localized structures can be generated and sustained from an incoherent source in
      quadratic nonlinear media. This phenomenon, which relies on the convection
      between the waves interacting in the medium, leads to the formation of a novel
      type of three-wave parametric soliton composed of both coherent and incoherent
      fields.

PMID- 11289844
TI  - Ordered and self-disordered dynamics of holes and defects in the one-dimensional
      complex Ginzburg-Landau equation.
AB  - We study the dynamics of holes and defects in the 1D complex Ginzburg-Landau
      equation in ordered and chaotic cases. Ordered hole-defect dynamics occurs when
      an unstable hole invades a plane wave state and periodically nucleates defects
      from which new holes are born. The results of a detailed numerical study of these
      periodic states are incorporated into a simple analytic description of isolated
      "edge" holes. Extending this description, we obtain a minimal model for general
      hole-defect dynamics. We show that interactions between the holes and a self
      disordered background are essential for the occurrence of spatiotemporal chaos in
      hole-defect states.

PMID- 11289843
TI  - Phase separation in a chaotic flow.
AB  - The phase separation between two immiscible liquids advected by a bidimensional
      velocity field is investigated numerically by solving the corresponding Cahn
      Hilliard equation. We study how the spinodal decomposition process depends on the
      presence-or absence-of Lagrangian chaos. A fully chaotic flow, in particular,
      limits the growth of domains, and for unequal volume fractions of the liquids, a
      characteristic exponential distribution of droplet sizes is obtained. The
      limiting domain size results from a balance between chaotic mixing and spinodal
      decomposition, measured in terms of Lyapunov exponent and diffusivity constant,
      respectively.

PMID- 11289845
TI  - Curing coupled-bunch instabilities with uneven fills.
AB  - A new, unified theoretical description of coupled-bunch instabilities in unevenly
      filled storage rings is presented. Uneven-fill longitudinal dynamics are
      explained in terms of two physical phenomena: fill-induced tune-spread damping
      and modulation coupling of strong even-fill eigenmodes. The latter is also
      present in the transverse plane. The analysis yields simple criteria for
      optimizing fill shapes to reduce the growth rates of the most unstable modes.
      Experimental results from the ALS and PEP-II are shown to be in good agreement
      with the theory.

PMID- 11289846
TI  - Anomalous dispersion behavior of multiple-wave X-ray diffraction at absorption
      edges: determination of phase change at resonance.
AB  - The effects of anomalous dispersion (resonance) on multiple reflection of x rays
      and their interference in crystals at atomic absorption edges are studied.
      Intensity ratios of two inversion-symmetry-related multiple diffractions at or
      near absorption edges exhibit highly phase-sensitive profiles with strong
      asymmetric characteristics, unlike those far from the edges. A new resonance
      perturbation Bethe approach is developed to explain this behavior. This leads to
      direct determination of the phase change for x-ray reflections at resonance.

PMID- 11289847
TI  - Picosecond X-ray diffraction probed transient structural changes in organic
      solids.
AB  - In this Letter, we report on the experimental characterization of the geometry of
      short-lived electronically excited states in organic solids by time-resolved x
      ray diffraction. Here, the structure factor of the organic crystal is measured as
      a function of time. Since this technique gives complete structural information,
      it is a very useful tool for learning more about atom motions on the excited
      state energy surface-"beyond" the broad band typical of conventional
      spectroscopy. Although we used molecular crystals rather than free molecules, the
      compounds show detectable transient structural changes on the ps to ns time scale
      in our study.

PMID- 11289848
TI  - Stereoscopic microscopy of atomic arrangement by circularly polarized-light
      photoelectron diffraction.
AB  - A principle for stereoscopic photographs that enables viewing three-dimensional
      atomic arrangements is proposed. The azimuthal shifts of forward-focusing peaks
      in the photoelectron diffraction pattern obtained by left and right helicity
      lights enables a stereoscopic image when the two images are, respectively, viewed
      by the left eye and the right eye simultaneously. By taking advantage of this
      phenomenon, a display-type spherical-mirror analyzer can obtain stereoscopic
      photographs directly on the screen without any computer-aided conversion process.

PMID- 11289849
TI  - Evidence of double criticality in a fluid model with density-dependent
      interactions.
AB  - Evidence of a liquid-liquid equilibrium in simple fluids has recently been
      exposed for a density-dependent pair potential in the framework of a van der
      Waals theory. Here this double criticality is investigated by means of computer
      simulation, a perturbation theory, and integral equation theory. It is found that
      the critical point estimated from the integral equation thermodynamics is not
      associated with divergent correlations. To cope with these features, a special
      simulation procedure, based on the definition of local densities, is devised.
      Monte Carlo calculations confirm the existence of two critical points, in
      agreement with the predictions of perturbation theory.

PMID- 11289850
TI  - Equilibrium dynamics in the nondiffusive regime of an entangled polymer blend.
AB  - The dynamics of compositional fluctuations in a miscible, entangled homopolymer
      blend of poly(ethylene oxide) and poly(methyl methacrylate) were studied on
      length scales smaller than the polymer radii of gyration, and for times
      comparable to the polymers' disentanglement time. The measured relaxation rates
      are consistent with predictions of the reptation model, as expressed via the
      dynamic random-phase approximation. Moreover, the observed mode amplitudes allow
      for an estimate of the entanglement length in the blend.

PMID- 11289851
TI  - Novel structures and properties of gold nanowires.
AB  - The structures of free-standing gold nanowires are studied by using molecular
      dynamics-based genetic algorithm simulations. Helical and multiwalled cylindrical
      structures are found for the thinner nanowires, while bulk-like fcc structures
      eventually form in the thicker nanowires up to 3 nm in diameter. This
      noncrystalline-crystalline transition starts from the core region of nanowires.
      The vibrational, electronic, and transport properties of nanowires are
      investigated based on the optimal structures. Bulklike behaviors are found for
      the vibrational and electronic properties of the nanowires with fcc crystalline
      structure. The conductance of nanowires generally increases with wire diameter
      and depends on the wire structure.

PMID- 11289852
TI  - Efficient, multiple-range random walk algorithm to calculate the density of
      states.
AB  - We present a new Monte Carlo algorithm that produces results of high accuracy
      with reduced simulational effort. Independent random walks are performed
      (concurrently or serially) in different, restricted ranges of energy, and the
      resultant density of states is modified continuously to produce locally flat
      histograms. This method permits us to directly access the free energy and
      entropy, is independent of temperature, and is efficient for the study of both
      1st order and 2nd order phase transitions. It should also be useful for the study
      of complex systems with a rough energy landscape.

PMID- 11289853
TI  - Phase equilibria of size-asymmetric primitive model electrolytes.
AB  - The low-temperature phase coexistence of size-asymmetric primitive model
      electrolyte solutions has been investigated by means of Monte Carlo simulations.
      Binodal curves and critical parameters are reported as a function of size ratio
      lambda = sigma(+)/sigma(-) in the range 0.05 to 1. Both the critical temperature
      and the critical density are found to decrease as lambda decreases. These trends
      are in conflict with available theoretical predictions. For highly asymmetric
      systems, the depression of the critical parameters is accompanied by the
      formation of large chainlike and ringlike structures, thereby giving rise to
      considerable finite-size effects.

PMID- 11289854
TI  - Entropy-vanishing transition and glassy dynamics in frustrated spins.
AB  - In an effort to understand the glass transition, the dynamics of a nonrandomly
      frustrated spin model has been analyzed. The phenomenology of the spin model is
      similar to that of a supercooled liquid undergoing the glass transition. The slow
      dynamics can be associated with the presence of extended stringlike structures
      which demarcate regions of fast spin flips. An entropy-vanishing transition, with
      the string density as the order parameter, is related to the observed glass
      transition in the spin model.

PMID- 11289855
TI  - Heterogeneities in supercooled liquids: a density-functional study.
AB  - A metastable state, characterized by a low degree of mass localization, is
      identified using density-functional theory (DFT). This free energy minimum,
      located through the proper evaluation of competing terms in the free energy
      functional, is independent of the specific form of the DFT used. Computer
      simulation results on particle motion indicate that this heterogeneous state
      corresponds to the deeply supercooled state.

PMID- 11289817
TI  - Comparative expressed-sequence-tag analysis of differential gene expression
      profiles in BmNPV-infected BmN cells.
AB  - To compare the gene expression profiles of uninfected and Bombyx mori
      nucleopolyhedrovirus (BmNPV)-infected BmN cells, we constructed four cDNA
      libraries for mock-infected cells, and cells at 2, 6, and 12 h postinfection
      (h.p.i.). A total of 2645 partial sequences obtained for expressed-sequence-tags
      (ESTs) from the libraries were categorized using BLAST searches of the public
      database and the BmNPV genome sequence. The following proportions of BmNPV
      derived ESTs were observed: 0.4, 4.5, and 57% at 2, 6, and 12 h.p.i,
      respectively. Moreover, 31 BmNPV open reading frames (ORFs) were newly identified
      for transcripts and the baculovirus-repeated ORFs (bro) showed the highest levels
      of expression in the 12 h.p.i. library. Most of the host genes decreased in
      number as the infection progressed. However, several, including cytochrome c
      oxidase 1, increased in the late stages of infection. Two apoptosis-related host
      genes were also identified.

PMID- 11289856
TI  - Liquid/vapor surface tension of metals: embedded atom method with charge gradient
      corrections.
AB  - Molecular dynamics simulations for three embedded atom method (EAM) function sets
      are used to determine the liquid/vapor surface tension gamma for Al, Ni, Cu, Ag,
      and Au. The three EAM models differ in both the functional forms employed and the
      fitting procedure used. All the EAM potentials underestimate gamma but one of the
      models performs consistently better than the others. We show that including a
      correction to the local charge density associated with gradients in the density
      together with exploiting the invariance of the EAM potentials to appropriate
      transformations in the charge density can lead to improved values for gamma, as
      well as for solid free surface energies, within existing EAM function sets.

PMID- 11289857
TI  - Critical adsorption in the weak surface field limit.
AB  - We study critical adsorption in the small surface field (h(1)) limit using a
      homologous series of critical liquid mixtures. The experiment data, in the one
      phase regime, is accurately described by a universal surface scaling function
      G+(z/xi(+),z/l(h)) at distance z from the interface with correlation length xi(+)
      and surface field length l(h) approximately absolute value of (h(1))(
      nu/Delta(1)), where h(1) approximately Deltasigma, the surface energy difference
      between the two components.

PMID- 11289859
TI  - Many-body diagrammatic expansion in a kohn-sham basis: implications for time
      dependent density functional theory of excited states.
AB  - We formulate diagrammatic rules for many-body perturbation theory which uses Kohn
      Sham Green's functions as basic propagators. The diagram technique allows one to
      study the properties of the dynamic nonlocal exchange-correlation (xc) kernel
      f(xc). We show that the spatial nonlocality of f(xc) is strongly frequency
      dependent. In particular, in extended systems the nonlocality range diverges at
      the excitation energies. This divergency is related to the discontinuity of the
      xc potential.

PMID- 11289858
TI  - Validity of the quasiharmonic analysis for surface thermal expansion of Ag(111).
AB  - For temperatures above 0.6T(m) (the bulk melting temperature) we show that the
      quasiharmonic approximation leads to increasingly larger values of the surface
      thermal expansion of Ag(111) as compared to that obtained from molecular dynamics
      simulations based on fully anharmonic interaction potentials. The inadequacy of
      the quasiharmonic approximation is traced to the excessive softening of the
      surface phonon frequencies. We discuss the validity of the quasiharmonic
      approximation for surfaces at elevated temperature, in view of recent x-ray
      scattering data on Ag(111).

PMID- 11289860
TI  - Localized 4f states and dynamic Jahn-Teller effect in PrO2.
AB  - Neutron spectroscopic measurements of the magnetic excitations in PrO2 reveal (1)
      sharp peaks characteristic of transitions between levels of the 4f(1)
      configuration of Pr4+ split by the cubic crystal field, and (2) broad bands of
      scattering centered near 30 and 160 meV. We present a simple model based on a
      vibronic Hamiltonian that accounts for these contrasting features of the data.
      The analysis shows that 90%+/-10% of the Pr ions have a localized 4f(1)
      configuration and provides strong evidence for a dynamic Jahn-Teller effect in
      the gamma(8) electronic ground state.

PMID- 11289861
TI  - Origin of giant optical nonlinearity in charge-transfer-mott insulators: a new
      paradigm for nonlinear optics.
AB  - Neither pure Mott insulators nor pure charge-transfer insulators have ever been
      considered as a possible candidate for nonlinear optical (NLO) materials since
      individually neither the strong correlation (U) nor the large charge transfer
      (Delta) is favorable to the NLO response. However, in their composites, charge
      transfer-Mott insulators, jointly Delta and U can enhance the hyperpolarizability
      (gamma) by guiding the ground states into the antiferromagnetic phase and the
      excited states into the charge-transfer phase. These Delta and U that maximize
      gamma form a unique golden Delta-U line, on which the recently observed giant
      nonlinear optical effect is just a single point, whose physical origin is that
      the system is driven into a phase-separated region for the ground and excited
      states. This novel mechanism may suggest a conceptually new paradigm to explore
      an even larger optical nonlinearity.

PMID- 11289862
TI  - Kondo tunneling through real and artificial molecules.
AB  - When an asymmetric double dot is hybridized with itinerant electrons, its singlet
      ground state and lowly excited triplet state cross, leading to a competition
      between the Zhang-Rice mechanism of singlet-triplet splitting in a confined
      cluster and the Kondo effect (which accompanies the tunneling through quantum dot
      under a Coulomb blockade restriction). The rich physics of an underscreened S = 1
      Kondo impurity in the presence of low-lying triplet-singlet excitations is
      exposed and estimates of the magnetic susceptibility and the electric conductance
      are presented, together with applications for molecule chemisorption on metallic
      substrates.

PMID- 11289863
TI  - Point-contact conductances from density correlations.
AB  - We formulate and prove an exact relation which expresses the moments of the two
      point conductance for an open disordered electron system in terms of certain
      density correlators of the corresponding closed system. As an application of the
      relation, we demonstrate that the typical two-point conductance for the Chalker
      Coddington model at criticality transforms like a two-point function in conformal
      field theory.

PMID- 11289864
TI  - Geometrical magnetothermopower in semiconductors.
AB  - The geometry of a semiconductor sample can be designed to create a very large
      change of the thermoelectric power in a magnetic field, similar to the effects of
      the sample geometry on the magnetoresistance. In semiconductors in which the
      minority carriers have a higher mobility than the majority carriers, this
      geometrical magnetothermopower can freeze out the contribution of the former to
      the total thermopower. This opens a new route toward high-efficiency
      thermoelectric materials. We also examine the thermoelectric reciprocity
      relations for these macroscopic systems.

PMID- 11289865
TI  - Spin degeneracy and conductance fluctuations in open quantum dots.
AB  - The dependence of conductance fluctuations on parallel magnetic field is used as
      a probe of spin degeneracy in open GaAs quantum dots. The variance of
      fluctuations at high parallel field is reduced from the low-field variance (with
      broken time-reversal symmetry) by factors ranging from roughly 2 in a 1 microm
      (2) dot to greater than 4 in 8 microm (2) dots. The factor of 2 is expected for
      Zeeman splitting of spin-degenerate channels. A possible explanation for the
      larger suppression based on field-dependent spin-orbit scattering is proposed.

PMID- 11289866
TI  - Spin-orbit effects in a GaAs quantum dot in a parallel magnetic field.
AB  - We analyze the effects of spin-orbit coupling on fluctuations of the conductance
      of a quantum dot fabricated in a GaAs heterostructure. Counterintuitively we
      argue that spin-orbit effects may become important in the presence of a large
      parallel magnetic field B( parallel), even if they are negligible for B(
      parallel) = 0. This should be manifest in the level repulsion of a closed dot,
      and in reduced conductance fluctuations in dots with a small number of open
      channels in each lead, for large B( parallel). Our picture is consistent with the
      experimental observations of Folk et al.

PMID- 11289867
TI  - Quasiparticle effects on tunneling currents: a study of C2H4 adsorbed on the
      Si(001)- (2 x 1) surface.
AB  - We present a first-principles calculation of the quasiparticle electronic
      structure of ethylene adsorbed on the dimer reconstructed Si(001)-(2x1) surface.
      Within the GW approximation, the self-energy corrections for the adsorbate states
      are found to be about 1.5 eV larger than those for the states derived from bulk
      silicon. The calculated quasiparticle band structure is in excellent agreement
      with photoemission spectra. Finally, the effects of the quasiparticle corrections
      on the scanning tunneling microscope images of the adsorbed molecules are shown
      to be important as the lowering of the C2H4 energy levels within GW strongly
      reduces their tunneling probability.

PMID- 11289868
TI  - Shot noise by quantum scattering in chaotic cavities.
AB  - We have experimentally studied shot noise of chaotic cavities defined by two
      quantum point contacts in series. The cavity noise is determined as (1/4)2e/I/ in
      agreement with theory and can be well distinguished from other contributions to
      noise generated at the contacts. Subsequently, we have found that cavity noise
      decreases if one of the contacts is further opened and reaches nearly zero for a
      highly asymmetric cavity. Heating inside the cavity due to electron-electron
      interaction can slightly enhance the noise of large cavities and is also
      discussed quantitatively.

PMID- 11289869
TI  - Signatures of spin pairing in chaotic quantum dots.
AB  - Coulomb blockade resonances are measured in a GaAs quantum dot in which both
      shape deformations and interactions are small. The parametric evolution of the
      Coulomb blockade peaks shows a pronounced pair correlation in both position and
      amplitude, which is interpreted as spin pairing. As a consequence, the nearest
      neighbor distribution of peak spacings can be well approximated by a modified
      bimodal Wigner surmise, in which interactions are taken into account beyond the
      constant interaction model.

PMID- 11289870
TI  - Transverse Josephson plasma mode in T* phase SmLa(1-x)Sr(x)CuO(4-delta) single
      crystals.
AB  - Far-infrared reflectivity along the c axis in T* phase SmLa(1-x)Sr(x)CuO(4-delta)
      single crystals is measured down to 8 cm(-1). Below T(c), the conductivity peak
      is observed at 25 cm(-1) for x = 0.15 ( T(c) = 30 K) along with two reflectivity
      edges at 13 and 27 cm(-1). The conductivity peak is attributed to the transverse
      Josephson plasma mode between two longitudinal Josephson plasma modes, while the
      oscillator strength of the peak is found to be smaller than that calculated using
      the Josephson-coupled multilayer model. The difference is explained by assuming
      that only a few junctions at the disordered (La,Sr)(2)O(2-delta) block layer take
      part in the plasma oscillation with omega(pI(')) = 27 cm(-1).

PMID- 11289871
TI  - Depinning transition of a two-dimensional vortex lattice in a commensurate
      periodic potential.
AB  - We use Monte Carlo simulations of the 2D one component Coulomb gas on a
      triangular lattice, to study the depinning transition of a 2D vortex lattice in a
      commensurate periodic potential. A detailed finite size scaling analysis
      indicates this transition to be first order. No significant changes in behavior
      were found as vortex density was varied over a wide range.

PMID- 11289872
TI  - Quantum melting of the quasi-two-dimensional vortex lattice in kappa-
      (ET)2Cu(NCS)(2).
AB  - We report torque magnetization measurements in regions of the mixed state phase
      diagram ( B approximately mu(o)H(c2) and T(c)/10(3)) of the organic
      superconductor kappa-(ET)2Cu(NCS)(2), where quantum fluctuations are expected to
      dominate thermal effects. Over most of the field range below the irreversibility
      line ( B(irr)), magnetothermal instabilities are observed in the form of flux
      jumps. The abrupt cessation of these instabilities just below B(irr) indicates a
      quantum melting transition from a quasi-two-dimensional vortex lattice phase to a
      quantum liquid phase.

PMID- 11289873
TI  - Finite-size scaling for the ising model on the Mobius strip and the klein bottle.
AB  - We study the finite-size scaling properties of the Ising model on the Mobius
      strip and the Klein bottle. The results are compared with those of the Ising
      model under different boundary conditions, that is, the free, cylindrical, and
      toroidal boundary conditions. The difference in the magnetization distribution
      function p(m) for various boundary conditions is discussed in terms of the number
      of the percolating clusters and the cluster size. We also find interesting aspect
      ratio dependence of the value of the Binder parameter at T = T(c) for various
      boundary conditions. We discuss the relation to the finite-size correction
      calculations for the dimer statistics.

PMID- 11289874
TI  - Magnetic behavior of na films with Fe, Co, and Ni impurities.
AB  - Thin films of Na with Fe, Co, and Ni impurities are investigated. The
      magnetization of the impurities is measured by means of the anomalous Hall
      resistance. Fe and Co show a moment of about 6mu(B), while for Ni no moment is
      detected. Furthermore, the magnetic dephasing of the conduction electrons is
      measured by means of weak localization. The dephasing rate 1/tau(phi) of the 3d
      impurities differ qualitatively. For Fe impurities, 1/tau(phi) is so large that
      it cannot be measured. For Co, 1/tau(phi) has a moderate value while Ni shows
      hardly a dephasing effect at all.

PMID- 11289875
TI  - Experimental evidence for intra-atomic noncollinear magnetism at thin film probe
      tips.
AB  - The energy-dependent spin-density orientation (SDO) at the apex of thin magnetic
      film tips is studied by spin-polarized scanning tunneling spectroscopy (SP-STS)
      at different bias voltages. At most energies the SDO is collinear with the tip
      magnetization resulting in a domain or domain-wall contrast in SP-STS images of
      out-of-plane magnetized samples measured with Gd or Fe coated tips, respectively.
      For some bias voltages, however, the SDO of the tip is found to be almost
      perpendicular to its magnetization. This result is explained in terms of intra
      atomic noncollinear magnetism.

PMID- 11289876
TI  - Strongly enhanced orbital moments and anisotropies of adatoms on the Ag(001)
      surface.
AB  - We present ab initio calculations for orbital moments and anisotropy energies of
      3d and 5d adatoms on the Ag(001) surface, based on density functional theory,
      including Brooks' orbital polarization (OP) term, and applying a fully
      relativistic Korringa-Kohn-Rostoker-Green's function method. In general, we find
      unusually large orbital moments and anisotropy energies, e.g., in the 3d series,
      2.57 mu(B) and +74 meV for Co, and, in the 5d series, 1.78 mu(B) and +42 meV for
      Os. These magnetic properties are determined mainly by the OP and even exist
      without spin-orbit coupling.

PMID- 11289877
TI  - Gateable suppression of spin relaxation in semiconductors.
AB  - The decay of spin memory in a 2D electron gas is found to be suppressed close to
      the metal-insulator transition. By dynamically probing the device using ultrafast
      spectroscopy, relaxation of optically excited electron spin is directly measured
      as a function of the carrier density. Motional narrowing favors spin preservation
      in the maximally scattered but nonlocalized electronic states. This implies that
      the spin-relaxation rate can be both tuned in situ and specifically engineered in
      appropriate device geometries.

PMID- 11289878
TI  - Vibrational anharmonicities revealed by coherent two-dimensional infrared
      spectroscopy.
AB  - Two-dimensional infrared photon echo spectroscopy has been used to describe the
      anharmonic nuclear potential of two coupled molecular vibrations. The two
      dimensional spectrum shows diagonal and off-diagonal features, each composed of
      two peaks. The splitting between these peaks is directly related to the
      anharmonicity, while the relative amplitude of the diagonal and off-diagonal
      features describes the projection angle between interacting dipoles.

PMID- 11289879
TI  - Wave packet dynamics in a quasi-one-dimensional metal-halogen complex studied by
      ultrafast time-resolved spectroscopy.
AB  - An ultrafast optical response is studied in a quasi-one-dimensional halogen
      bridged mixed-valence metal complex [Pt(en)(2)] [Pt(en)2I2] (ClO4)(4) with
      ultrafast time resolution. Wave packet motions both in the ground and self
      trapped exciton (STE) states are observed as oscillatory modulations in the time
      resolved reflectivity. The wave packet motion on the STE potential surface begins
      after about 50 fs with respect to the photoexcitation. This delay is attributed
      to the lattice relaxation from the free exciton state to the STE state.

PMID- 11289880
TI  - Quantum computing of quantum chaos and imperfection effects.
AB  - We study numerically the imperfection effects in the quantum computing of the
      kicked rotator model in the regime of quantum chaos. It is shown that there are
      two types of physical characteristics: for one of them the quantum computation
      errors grow exponentially with the number of qubits in the computer, while for
      the other the growth is polynomial. A certain similarity between classical and
      quantum computing errors is also discussed.

PMID- 11289881
TI  - Efficiently learning multilayer perceptrons.
AB  - A learning algorithm for multilayer perceptrons is presented which is based on
      finding the principal components of a correlation matrix computed from the
      example inputs and their target outputs. For large networks our procedure needs
      far fewer examples to achieve good generalization than traditional on-line
      algorithms.

PMID- 11289882
TI  - Transitions between orbits of resonance attractors for spiral waves.
AB  - Spiral waves rotating in a thin layer of the light-sensitive Belousov-Zhabotinsky
      reaction can be controlled by the application of short light pulses at instants
      corresponding to the passage of a wave front through a measuring point. It is
      shown that such a feedback results in a drift of the spiral wave core along a
      discrete set of stable circular orbits centered at the measuring point, in good
      quantitative agreement with the theory of the resonance attractor recently
      developed. Variations of parameters in the feedback loop initiate transitions
      between orbits of different size. Thus a spiral wave drift can be induced along a
      snail-shaped trajectory with permanently growing distance from the measuring
      point.

PMID- 11289883
TI  - Retarded learning: rigorous results from statistical mechanics.
AB  - We study learning of probability distributions characterized by an unknown
      symmetry direction. Based on an entropic performance measure and the variational
      method of statistical mechanics we develop exact upper and lower bounds on the
      scaled critical number of examples below which learning of the direction is
      impossible. The asymptotic tightness of the bounds suggests an asymptotically
      optimal method for learning nonsmooth distributions.

PMID- 11289884
TI  - Hairpin formation and elongation of biomolecules.
AB  - We introduce a model of thermalized conformations in space of RNA-or single
      stranded DNA-molecules, which includes the possibility of hairpin formation. This
      model contains the usual secondary structure information, but extends it to the
      study of one element of the ternary structure, namely the end-to-end distance.
      The computed force-elongation characteristics are in good agreement with some
      recent measurements on single stranded DNA molecules.

PMID- 11289885
TI  - Elastically driven linker aggregation between two semiflexible polyelectrolytes.
AB  - The behavior of mobile linkers connecting two semiflexible charged polymers, such
      as polyvalent counterions connecting DNA or F-actin chains, is studied
      theoretically. The chain bending rigidity induces an effective repulsion between
      linkers at large distances while the interchain electrostatic repulsion leads to
      an effective short-range interlinker attraction. We find a rounded phase
      transition from a dilute linker gas where the chains form large loops between
      linkers to a dense disordered linker fluid connecting parallel chains. The onset
      of chain pairing occurs within the rounded transition.

PMID- 11289886
TI  - Effects of synaptic noise and filtering on the frequency response of spiking
      neurons.
AB  - Noise can have a significant impact on the response dynamics of a nonlinear
      system. For neurons, the primary source of noise comes from background synaptic
      input activity. If this is approximated as white noise, the amplitude of the
      modulation of the firing rate in response to an input current oscillating at
      frequency omega decreases as 1/square root[omega] and lags the input by 45
      degrees in phase. However, if filtering due to realistic synaptic dynamics is
      included, the firing rate is modulated by a finite amount even in the limit omega
      ->infinity and the phase lag is eliminated. Thus, through its effect on noise
      inputs, realistic synaptic dynamics can ensure unlagged neuronal responses to
      high-frequency inputs.

PMID- 11289887
TI  - From single- to multiple-pPhoton decoherence in an atom interferometer.
AB  - We measure the decoherence of a spatially separated atomic superposition due to
      spontaneous photon scattering. We observe a qualitative change in decoherence
      versus separation as the number of scattered photons increases, and verify
      quantitatively the decoherence rate constant in the many-photon limit. Our
      results illustrate an evolution of decoherence consistent with general models
      developed for a broad class of decoherence phenomena.

PMID- 11289888
TI  - Experimental observation of Beliaev coupling in a Bose-Einstein condensate.
AB  - We report the first experimental observation of Beliaev coupling between
      collective excitations of a Bose-Einstein condensed gas. Beliaev coupling is not
      predicted by the Gross-Pitaevskii equation and so this experiment tests
      condensate theory beyond the mean field approximation. Measurements of the
      amplitude of a high frequency scissors mode show that the Beliaev process
      transfers energy to a lower-lying mode and then back and forth between these
      modes, unlike Landau processes which lead to a monotonic decrease in amplitude.
      To enhance the Beliaev process we adjusted the geometry of the magnetic trapping
      potential to give a frequency ratio of 2 to 1 between the two scissors modes.

PMID- 11289889
TI  - Analytical method for yrast line states in interacting Bose-Eeinstein
      condensates.
AB  - We propose a method to investigate the energy eigenvalue problem and
      corresponding yrast line for harmonically trapped interacting N-boson systems.
      This method is particularly simple and effective to obtain the explicit
      analytical expressions of low-L energy eigenstates with L denoting systems' total
      angular momentum but with an arbitrarily large N. We have derived the explicit
      analytical results for L = 0,1,....,9 and discussed the yrast line for these low-
      L energy eigenstates.

PMID- 11289890
TI  - Explosion of a collapsing Bose-Einstein condensate.
AB  - We show that elastic collisions between atoms in a Bose-Einstein condensate with
      attractive interactions can lead to an explosion that ejects a large fraction of
      the collapsing condensate. We study variationally the dynamics of this explosion
      and find excellent agreement with recent experiments on magnetically trapped
      85Rb. We also determine the energy and angular distribution of the ejected atoms
      during the collapse.

PMID- 11289891
TI  - Fractional transport equations for Levy stable processes.
AB  - The influence functional method of Feynman and Vernon is used to obtain a quantum
      master equation for a system subjected to a Levy stable random force. The
      corresponding classical transport equations for the Wigner function are then
      derived, both in the limits of weak and strong friction. These are fractional
      extensions of the Klein-Kramers and the Smoluchowski equations. It is shown that
      the fractional character acquired by the position in the Smoluchowski equation
      follows from the fractional character of the momentum in the Klein-Kramers
      equation. Connections among fractional transport equations recently proposed are
      clarified.

PMID- 11289892
TI  - Evolution of cosmological perturbations in a brane-universe.
AB  - In our present Letter, we analyze the impact of the existence of extra dimensions
      on cosmology, in particular, on the evolution of cosmological perturbations. For
      a five-dimensional anti-de Sitter spacetime where ordinary matter is confined to
      a brane-universe, the equations governing the cosmological perturbations are
      presented in a form very close to the equations of standard cosmology. Two types
      of corrections appear: corrections due to the unconventional evolution of the
      homogeneous solution, which change the background-dependent coefficients of the
      equations, and corrections due to the curvature along the fifth dimension, which
      act as source terms in the evolution equations.

PMID- 11289893
TI  - QCD phase transition in the inhomogeneous universe.
AB  - We investigate a new mechanism for the cosmological QCD phase transition:
      inhomogeneous nucleation. The primordial temperature fluctuations, measured to be
      deltaT/T approximately 10(-5), are larger than the tiny temperature interval in
      which bubbles would form in the standard picture of homogeneous nucleation. Thus
      the bubbles nucleate at cold spots. We find the typical distance between bubble
      centers to be a few meters. This exceeds the estimates from homogeneous
      nucleation by 2 orders of magnitude. The resulting baryon inhomogeneities may
      affect primordial nucleosynthesis.

PMID- 11289894
TI  - On the significance of the vector potential squared.
AB  - We consider the gauge potential A and argue that the minimum value of the volume
      integral of A2 (in Euclidean space) may have physical meaning, particularly in
      connection with the existence of topological structures. A lattice simulation
      comparing compact and noncompact "photodynamics" shows a jump in this quantity at
      the phase transition, supporting this idea.

PMID- 11289895
TI  - Weak and electromagnetic nuclear decay signatures for neutrino reactions in Super
      Kamiokande.
AB  - We suggest the study of events in the Super-Kamiokande neutrino data due to
      charged- and neutral-current neutrino reactions followed by weak and/or
      electromagnetic decays of struck nuclei and fragments thereof. This study could
      improve the prospects of obtaining evidence for tau production from nu(mu)-
      >nu(tau) oscillations and could augment the data sample used to disfavor nu(mu)-
      >nu(sterile) oscillations.

PMID- 11289896
TI  - Precise measurement of the positive muon anomalous magnetic moment.
AB  - A precise measurement of the anomalous g value, a(mu) = (g-2)/2, for the positive
      muon has been made at the Brookhaven Alternating Gradient Synchrotron. The result
      a(mu+) = 11 659 202(14) (6) x 10(-10) (1.3 ppm) is in good agreement with
      previous measurements and has an error one third that of the combined previous
      data. The current theoretical value from the standard model is a(mu)(SM) = 11 659
      159.6(6.7) x 10(-10) (0.57 ppm) and a(mu)(exp) - a(mu)(SM) = 43(16) x 10(-10) in
      which a(mu)(exp) is the world average experimental value.

PMID- 11289898
TI  - Moments of the neutron charge form factor and the N --> Delta quadrupole
      transition.
AB  - Recent data allow a new parametrization of the neutron charge form factor GnE. A
      parameter-free quark-model relation between GnE and the N-->Delta quadrupole form
      factor G(N-->Delta)C2 is used to predict G(N-->Delta)C2 from GnE data. In
      particular, <r2n> is related to N-->Delta quadrupole moment Q(N-->Delta), while
      <r4n> connects to the N-->Delta quadrupole transition radius <r2(N-->Delta)>.
      From the latter we derive an experimental value for the charge radius of the
      light constituent quarks r(gamma(q)) = 0.8 fm. Finally, the C2/M1 ratio in pion
      electroproduction is predicted from the elastic neutron form factor data.

PMID- 11289899
TI  - Investigation of the correlation potential from Kohn-Sham perturbation theory.
AB  - Perturbation theory on the basis of the Kohn-Sham Hamiltonian leads to an
      implicit density functional for the correlation energy E(c). In this contribution
      we investigate the corresponding correlation potential v(c). It is shown that for
      finite systems the v(c) obtained by direct application of the optimized potential
      method diverges in the asymptotic region. The presence of unoccupied states,
      inherent in any perturbative form of E(c), is identified as the origin of this
      unphysical behavior. An approximate variational procedure is developed in order
      to avoid this difficulty. The potential resulting from this method qualitatively
      reproduces the shell structure of the exact atomic v(c).

PMID- 11289900
TI  - Above-threshold dissociative ionization in the intermediate intensity regime.
AB  - The problem of dissociative ionization at intermediate intensities ( 10(10)
      10(12) W cm(-2)) was studied using the example of I2 and the technique of
      velocity map imaging. Several new phenomena were observed, including a continuous
      distribution of recoil energies peaked at zero-kinetic energy, a set of constant
      dissociative ionic states, and strong anisotropy of the fragment velocity
      distribution that is diminished by intermediate resonances.

PMID- 11289901
TI  - NO rotational orientation following 308 nm photodissociation of NO2.
AB  - The rotational angular momentum orientation and alignment of the NO fragments
      generated via linearly polarized 308 nm photodissociation of NO2 has been
      determined using laser induced fluorescence. By observing the dependence of the
      photofragment NO Doppler-resolved transition line shapes on experimental
      geometry, it has proved possible to determine multipole moments of the
      photofragment angular momentum distribution up to, and including, rank 3. The
      implications of the results for the mechanism of the dissociation are considered.

PMID- 11289897
TI  - Measurement of the lambda(+)(c) lifetime.
AB  - The Lambda+c lifetime is measured using 9.0 fb(-1) of e+e- annihilation data
      collected on or just below the Upsilon(4S) resonance with the CLEO II.V detector
      at CESR. Using an unbinned maximum likelihood fit, the Lambda+c lifetime is
      measured to be 179.6+/-6.9(stat)+/-4.4(syst) fs. The precision of this colliding
      beam measurement is comparable to other measurements, which are based on fixed
      target experiments, with different systematic uncertainties.

PMID- 11289902
TI  - Resonant coupling in the formation of ultracold ground state molecules via
      photoassociation.
AB  - We demonstrate the existence of a new mechanism for the formation of ultracold
      molecules via photoassociation of cold cesium atoms. The experimental results,
      interpreted with numerical calculations, suggest that a resonant coupling between
      vibrational levels of the 0+u (6s+6p1/2) and (6s+6p3/2) states enables formation
      of ultracold molecules in vibrational levels of the ground state well below the
      6s+6s dissociation limit. Such a scheme should be observable with many other
      electronic states and atomic species.

PMID- 11289903
TI  - Strong correlations in the He ground state momentum wave function observed in the
      fully differential momentum distributions for the p + He transfer ionization
      process.
AB  - The four-particle process of proton-helium transfer ionization has been studied
      using cold target recoil ion momentum spectroscopy to measure the momenta of all
      three particles in the final state. Most of the electrons are emitted in the H0
      scattering plane and in the backward direction. The final state momentum
      distributions show discrete structures very different from those expected for
      uncorrelated capture and ionization. The measured momentum pattern is interpreted
      to be due to a new transfer ionization reaction channel which results from strong
      correlations in the initial He ground state momentum wave function.

PMID- 11289904
TI  - Stagger-and-step method: detecting and computing chaotic saddles in higher
      dimensions.
AB  - Chaotic transients occur in many experiments including those in fluids, in
      simulations of the plane Couette flow, and in coupled map lattices. These
      transients are caused by the presence of chaotic saddles, and they are a common
      phenomenon in higher dimensional dynamical systems. For many physical systems,
      chaotic saddles have a big impact on laboratory measurements, but there has been
      no way to observe these chaotic saddles directly. We present the first general
      method to locate and visualize chaotic saddles in higher dimensions.

PMID- 11289905
TI  - Control of chaos via an unstable delayed feedback controller.
AB  - Delayed feedback control of chaos is well known as an effective method for
      stabilizing unstable periodic orbits embedded in chaotic attractors. However, it
      had been shown that the method works only for a certain class of periodic orbits
      characterized by a finite torsion. Modification based on an unstable delayed
      feedback controller is proposed in order to overcome this topological limitation.
      An efficiency of the modified scheme is demonstrated for an unstable fixed point
      of a simple dynamic model as well as for an unstable periodic orbit of the Lorenz
      system.

PMID- 11289906
TI  - Driven Rydberg atoms reveal quartic level repulsion.
AB  - The dynamics of Rydberg states of a hydrogen atom subjected simultaneously to
      uniform static electric field and two microwave fields with commensurate
      frequencies is considered in the range of small field amplitudes. In the certain
      range of the parameters of the system the classical secular motion of the
      electronic ellipse reveals chaotic behavior. Quantum mechanically, when the fine
      structure of the atom is taken into account, the energy level statistics obey
      predictions appropriate for the symplectic Gaussian random matrix ensemble.

PMID- 11289907
TI  - Collective directional transport in coupled nonlinear oscillators without
      external bias.
AB  - Directed collective motion in a circular array of unidirectionally coupled
      oscillators with symmetric potential is obtained numerically in the absence of
      external bias. This striking feature is interpreted as the effect of the
      spontaneous breaking of temporal symmetry of the coupling. It is revealed that a
      proper match of various control parameters is important in generating an optimal
      coherent global transport. Noise-sustained directed transport is also observed,
      and the related stochastic resonance in an autonomous system is identified.

PMID- 11289908
TI  - X-ray amplification by laser controlled coherent bremsstrahlung.
AB  - A coherent x-ray generation scheme is proposed which involves characteristics of
      free electron lasers and atomic high harmonic generation schemes. A thin solid
      layer or any other periodic atomic structure with limited dimensions is exposed
      to a short, superintense laser pulse. The electrons are extracted from the layer
      due to the extreme force and penetrate periodically through the ionic structure.
      Consequently, thousands of harmonics of the laser radiation field are shown to
      coherently amplify along the interaction length. The small signal gain of the
      generated x-ray radiation exceeds that arising from the multiphoton Compton
      process in plasmas and is competitive with that in the leading x-ray free
      electron lasers.

PMID- 11289909
TI  - Dynamic soliton-like modes.
AB  - Incoherent optical spatial solitons require noninstantaneous nonlinearity, i.e.,
      the local intensity fluctuation of the solitons must be faster than the medium
      can respond. Observing partially incoherent bicomponent solitons, we find that
      there exists a threshold speed. When the fluctuation of the soliton intensity,
      resulting from the time-varying interference of its constituent modes, is below
      the threshold, the soliton beam and its induced waveguide oscillate violently.
      Just above the threshold, the soliton-induced waveguide is observed to be dragged
      by the soliton beam.

PMID- 11289910
TI  - Orbital and spin photon angular momentum transfer in liquid crystals.
AB  - All-optical angular control of the molecular alignment in liquid-crystal films is
      demonstrated using a laser beam having an elliptically shaped intensity profile.
      The material birefringence is unimportant, as proven by the fact that good
      alignment is obtained with unpolarized light. This raises the possibility of
      achieving optical angular control of transparent isotropic bodies. A general
      theoretical approach, based on light and matter angular momentum conservation,
      shows that the optical alignment is due to the internal compensation between the
      transfer of the orbital and the spin part of angular momentum of the incident
      photons to the material.

PMID- 11289911
TI  - Confined band gap in an air-bridge type of two-dimensional AlGaAs photonic
      crystal.
AB  - The transmittance spectrum for an air-bridge type of AlGaAs photonic crystal (PC)
      slabs successfully fabricated was measured. It is found that the observed
      spectrum is consistent with both the theoretical band structure and the
      calculated one. Moreover, the transmittance due to the modes below the light line
      is found to be almost 100%, indicating that the guided modes should exist. The
      respective stop bands are observed in the gamma-M direction for TM-like and TE
      like modes, implying that a photonic band gap should exist for the TE-like guided
      modes. The present PC is very suited for controlling the radiation field.

PMID- 11289912
TI  - Passive stabilization of capillary bridges in air with acoustic radiation
      pressure.
AB  - Long liquid capillary bridges are normally unstable because of the growth of a
      mode where one end becomes slender while the other becomes rotund. This Rayleigh
      Plateau instability was suppressed for weightless bridges on NASA's KC-135
      aircraft by placing the bridge in an acoustic standing wave. With an appropriate
      acoustic wavelength and amplitude the radiation pressure automatically squeezes
      more on the rotund portion of the bridge so as to suppress the growth of the
      relevant capillary mode. Stabilization is a natural consequence of the
      interaction with the steady sound field.

PMID- 11289913
TI  - Ballistic-diffusive heat-conduction equations.
AB  - We present new heat-conduction equations, named ballistic-diffusive equations,
      which are derived from the Boltzmann equation. We show that the new equations are
      a better approximation than the Fourier law and the Cattaneo equation for heat
      conduction at the scales when the device characteristic length, such as film
      thickness, is comparable to the heat-carrier mean free path and/or the
      characteristic time, such as laser-pulse width, is comparable to the heat-carrier
      relaxation time.

PMID- 11289914
TI  - Coarsening in the presence of kinetic disorders: analogy to granular compaction.
AB  - We study the zero temperature dynamics in an Ising chain in the presence of a
      dynamically induced field that favors locally the " -" phase compared to the " +"
      phase. At late times, while the " +" domains coarsen as t(1/2), the " -" domains
      coarsen as t(1/2)log(t). Hence, at late times, the magnetization decays slowly as
      m(t) = -1+const/log(t). We establish this behavior both analytically within an
      independent interval approximation and numerically. Our model can be viewed as a
      simple model for granular compaction, where the system decays into a fully
      compact state (with all spins " -") in a slow logarithmic manner as seen in
      recent experiments on granular systems.

PMID- 11289915
TI  - Universal decay of scalar turbulence.
AB  - The asymptotic decay of passive scalar fields is solved analytically for the
      Kraichnan model, where the velocity has a short correlation time. At long times,
      two universality classes are found, both characterized by a distribution of the
      scalar-generally non-Gaussian-with global self-similar evolution in time.
      Analogous behavior is found numerically with a more realistic flow resulting from
      an inverse energy cascade.

PMID- 11289916
TI  - Oscillatory binary fluid convection in large aspect-ratio containers.
AB  - Direct numerical simulations of chevrons, blinking states, and repeated
      transients in binary fluid mixtures with a negative separation ratio heated from
      below are described. The calculations are performed in two-dimensional containers
      for experimental parameter values and boundary conditions. Quantitative agreement
      with the experiments of Kolodner [Phys. Rev. E 47, 1038 (1993)] is obtained, and
      the origin of the blinking and repeated transient states is elucidated.

PMID- 11289917
TI  - Collective resonance model of energy exchange in 3D nonequipartitioned beams.
AB  - Energy exchange between the longitudinal and transverse degrees of freedom of
      nonequipartitioned bunched beams (non-neutral plasmas) is investigated by means
      of 3D simulation. It is found that collective instability may lead to energy
      transfer in the direction of equipartition, without full progression to it, in
      certain bounded regions of parameter space where internal resonance conditions
      are satisfied, in good agreement with stability charts from an earlier derived 2D
      Vlasov analysis. Nonequipartitioned stable equilibria, however, exist in
      relatively wide regimes of parameter space. This provides evidence that such
      regimes may be safely used in the design of future high-intensity linacs.

PMID- 11289918
TI  - Mev X rays and photoneutrons from femtosecond laser-produced plasmas.
AB  - We demonstrate a novel method to monitor the total angular distribution of the
      spectrum of hard x-ray emission from a plasma generated with femtosecond laser
      pulses with an intensity of 5 x 10(18) W/cm2 on a solid target. Measured and
      calculated angular distributions of x rays show a pronounced anisotropy for MeV
      photon energies. We complemented the spectral information by demonstrating a
      (gamma,n) nuclear reaction with a tabletop laser system.

PMID- 11289919
TI  - Strong "quantum" chaos in the global ballooning mode spectrum of three
      dimensional plasmas.
AB  - The spectrum of ideal magnetohydrodynamic (MHD) pressure-driven (ballooning)
      modes in strongly nonaxisymmetric toroidal systems is difficult to analyze
      numerically owing to the singular nature of ideal MHD caused by lack of an
      inherent scale length. In this paper, ideal MHD is regularized by using a k-space
      cutoff, making the ray tracing for the WKB ballooning formalism a chaotic
      Hamiltonian billiard problem. The minimum width of the toroidal Fourier spectrum
      needed for resolving toroidally localized ballooning modes with a global
      eigenvalue code is estimated from the Weyl formula. This phase-space-volume
      estimation method is applied to two stellarator cases.

PMID- 11289920
TI  - Experimental evidence for gradient length-driven electron transport in tokamaks.
AB  - Energy transport by the electrons in a tokamak is examined in steady-state and
      power modulation experiments using electron cyclotron heating. The results are
      consistent with the assumption that temperature profiles are limited by a
      critical gradient length, leading to "stiff" profiles. The modulation experiments
      show that the stiffness factor increases with temperature. They strongly suggest
      that turbulence driven by the electron temperature gradient may be a dominant
      mechanism of electron transport. Although possibly not universal, these results
      are valid under various plasma conditions.

PMID- 11289921
TI  - Transient magnetic reconnection and unstable shear layers.
AB  - We study three-dimensional magnetic reconnection caused by the Kelvin-Helmholtz
      (KH) instability and differential rotation in subsonic and sub-Alfvenic flows.
      The flows, which are modeled by the resistive magnetohydrodynamic equations with
      constant resistivity, are stable in the direction of the magnetic field but
      unstable perpendicular to the magnetic field. Localized transient reconnection is
      observed on the KH time scale, and kinetic energy increases with decreasing
      resistivity. As in flux-transfer events in the Earth's magnetopause boundary
      layer, bipolar structures in the normal flux and bidirectional jetting away from
      reconnection zones are observed.

PMID- 11289922
TI  - Real-space imaging of atomic structure with white x rays.
AB  - The first real-space x-ray image of an atomic structure was obtained by
      illuminating a crystal with white synchrotron radiation. The internal
      photocurrent signal served as a probe of the x-ray interference field strength at
      the atomic sites and was accordingly measured as a function of illumination
      direction to record the two-dimensional image. This novel method of real-space
      imaging makes use of the fact that the interference field intensity is energy
      independent with respect to contributions from those scattering atoms which are
      brought via sample rotation into the forward scattering condition. In contrast,
      contributions from other atoms oscillate with energy and vanish for broadband
      illumination.

PMID- 11289924
TI  - Counterion phase transitions in dilute polyelectrolyte solutions.
AB  - In dilute solutions of rodlike polyelectrolytes some counterions are distributed
      far from polyions while others are located in their vicinity in the regions of
      cylindrical symmetry of the electrostatic potential. For these cylindrical
      regions around rodlike polyelectrolytes we find an exact solution of the
      nonlinear Poisson-Boltzmann equation for the case of nonzero net charge in these
      regions. This exact solution implies three qualitatively different phases of
      counterion distribution around the polyions with second order phase transitions
      between these phases.

PMID- 11289923
TI  - Atomically resolved images from near node photoelectron holography experiments on
      Al(111).
AB  - Szoke's concept for electron holography is hampered by forward scattering that
      dominates electron diffraction from electron point sources below the surface top
      layer. Forward scattering was proposed to be suppressed if the anisotropic nature
      of the electron source wave is exploited [T. Greber and J. Osterwalder, Chem.
      Phys. Lett. 256, 653 (1996)]. Experiments show a strong suppression of forward
      scattering in Al(111) if Al 2s photoelectrons (E(kin) = 952 eV) are measured near
      the nodal plane of the outgoing p wave. The holographic reconstruction from such
      diffraction data provides three dimensional images of atomic sites in unit cells
      with a size of more than 10 A.

PMID- 11289925
TI  - Decay characteristics of surface mounds with contrasting interlayer mass
      transport channels.
AB  - The decay characteristics of three-dimensional (3D) islands formed on surfaces
      are investigated theoretically considering two types of interlayer mass transport
      mechanisms. If an adatom on a given layer can easily descend from any site along
      the periphery of the layer, an optimal island slope and a constant terrace width
      will be selected during the decay. In contrast, if the adatom can descend
      primarily through selective (such as kinked) sites, the decay will be accompanied
      by a gradual increase in the island slope. These generic conclusions provide the
      basis for a microscopic understanding of the decay of nanostructures in fcc(111)
      and fcc(100) metal homoepitaxy and are applicable to other systems as well.

PMID- 11289926
TI  - Anomalous elastic response of silicon to uniaxial shock compression on nanosecond
      time scales.
AB  - We have used x-ray diffraction with subnanosecond temporal resolution to measure
      the lattice parameters of orthogonal planes in shock compressed single crystals
      of silicon (Si) and copper (Cu). Despite uniaxial compression along the (400)
      direction of Si reducing the lattice spacing by nearly 11%, no observable changes
      occur in planes with normals orthogonal to the shock propagation direction. In
      contrast, shocked Cu shows prompt hydrostaticlike compression. These results are
      consistent with simple estimates of plastic strain rates based on dislocation
      velocity data.

PMID- 11289927
TI  - Discrete solitons and breathers with dilute Bose-Einstein condensates.
AB  - We study the dynamical phase diagram of a dilute Bose-Einstein condensate (BEC)
      trapped in a periodic potential. The dynamics is governed by a discrete nonlinear
      Schrodinger equation: intrinsically localized excitations, including discrete
      solitons and breathers, can be created even if the BEC's interatomic potential is
      repulsive. Furthermore, we analyze the Anderson-Kasevich experiment [Science 282,
      1686 (1998)], pointing out that mean field effects lead to a coherent destruction
      of the interwell Bloch oscillations.

PMID- 11289928
TI  - Evidence for an instability near twice the fermi wave vector in the low
      electronic density liquid metal Li(NH3)4.
AB  - We report high-resolution inelastic x-ray scattering measurements in the metallic
      liquid Li(NH3)4, which to a good approximation can be treated as a dilute alkali
      metal. We see a well-defined excitation out to large momentum transfers. This
      excitation shows a strong softening at wave vectors near the first peak in the
      structure factor, which occurs near twice the Fermi momentum.

PMID- 11289929
TI  - Theoretical study of the lattice thermal conductivity in Ge framework
      semiconductors.
AB  - The lattice thermal conductivity of Ge clathrates is investigated by evaluating
      the linear response theory heat current correlation functions using molecular
      dynamics. Clathrate crystals with and without guest atoms in their fullerane
      cages are studied. In comparison with that of diamond-phase Ge, the clathrate
      conductivity is reduced by approximately 1 order of magnitude due to the open
      framework itself. The addition of an encapsulated (rattling) Sr guest atom
      produces a further order of magnitude reduction in the conductivity, making it
      comparable to that of amorphous Ge. Our results are consistent with experiments,
      and have impact on the search for improved thermoelectric materials.

PMID- 11289930
TI  - Novel magnetism in 3He nanoclusters.
AB  - The magnetic susceptibility of 3He nanoclusters embedded in a 4He matrix has been
      measured from 0.5 to 10 mK at pressures from 2.88 to 3.54 MPa. Even the lowest
      pressure clusters have a solid fraction in the region of the phase diagram where
      bulk solid is unstable. At 3.54 MPa, straight theta = -250 microK, equal to that
      of bulk 3He for v = 21.3 cm3/mole. For 2.88 MPa, straight theta = 140 microK,
      indicating a ferromagnetic tendency, similar to 2D films at some coverages. At
      intermediate pressures, chi has a peak near 1.05 mK, but with no discontinuity.
      Magnetic ordering in nanoclusters appears to be different than the U2D2 phase of
      bulk 3He.

PMID- 11289931
TI  - Renormalization-group calculation of the dependence on gravity of the surface
      tension and bending rigidity of a fluid interface.
AB  - The surface tension and the bending rigidity of a planar liquid-vapor interface
      in the presence of vanishing gravity are analyzed using the renormalization
      group. Based on the density functional theory of inhomogeneous fluids, we show
      that a term, quartic in the density fluctuations, can be added to the classical
      capillary-wave model so that a renormalization-group calculation can be
      performed. By comparing the outcome of such a calculation with rigorous results
      relating the direct correlation function with surface tension and bending
      rigidity, we find the scaling dependence of the latter on gravity. The results
      agree with the expected fact that the interface should become unstable as gravity
      vanishes.

PMID- 11289932
TI  - Unambiguous interpretation of atomically resolved force microscopy images of an
      insulator.
AB  - The (111) surface of CaF2 was imaged with dynamic mode scanning force microscopy
      and modeled using atomistic simulation. Both experiment and theory showed a clear
      triangular contrast pattern in images, and theory demonstrated that the contrast
      pattern is due to the interaction of a positive electrostatic potential tip with
      fluorine ions in the two topmost surface layers. We find a good agreement of
      position and relative height of scan line features between theory and experiment
      and thus establish for the first time an unambiguous identification of
      sublattices of an insulator imaged by force microscopy.

PMID- 11289933
TI  - Evidence from the surface morphology for nonlinear growth of epitaxial GaAs
      films.
AB  - The mesoscale morphology of homoepitaxial GaAs surfaces is explained with an
      anisotropic and nonlinear Kardar-Parisi-Zhang (KPZ) model in which adatoms are
      incorporated into the film from a metastable surface layer. Evaporation
      condensation between the film and the metastable layer is proposed as the
      microscopic physical origin of the KPZ description, as well as of the excess
      noise observed in the power spectral density. The parabolic mounds observed
      experimentally in films grown on rough substrates are in good agreement with the
      surface shape expected from the solution of the KPZ equation in the large
      amplitude limit.

PMID- 11289934
TI  - Nature of the Stranski-Krastanow transition during epitaxy of InGaAs on GaAs.
AB  - We report first quantitative measurements by energy-selected imaging in a
      transmission electron microscope of In segregation within an uncapped islanded
      In0.25Ga0.75As layer grown epitaxially on GaAs. This layer has the lowest In
      concentration at which islanding occurs and, then, only after a flat
      approximately 3 nm alloy layer has been formed. In buildup by segregation at the
      surface of this initial flat layer is considered the driving force for islanding
      and, importantly, the segregation process introduces the characteristic delay
      seen before the Stranski-Krastanow transition. We observe strong inhomogeneous In
      enrichment within the islands (up to x(In) approximately 0.6 at the apex) and a
      simultaneous In depletion in the remaining flat layer.

PMID- 11289935
TI  - Single-walled BN nanostructures.
AB  - We describe in situ synthesis and characterization of single-walled BN nanotubes
      terminated by fullerenelike structures using electron-cyclotron resonance
      nitrogen and electron beam boron sources onto polycrystalline tungsten
      substrates. Detailed comparisons of experimental high-resolution electron
      microscopy images and simulations based upon molecular models show a dominance of
      kinks and bends involving fourfold and eightfold ring structures as against
      fivefold or sevenfold which have been found with carbon. Analysis of the
      structures as a function of film thickness indicates that they are growing by
      addition of atoms to the exposed ends of single sheets, not at the substrate
      nanostructure interface.

PMID- 11289936
TI  - Disorder and interaction in 2D: exact diagonalization study of the Anderson
      Hubbard-Mott model.
AB  - We investigate, by numerically calculating the charge stiffness, the effects of
      random diagonal disorder and electron-electron interaction on the nature of the
      ground state in the 2D Hubbard model through the finite-size exact
      diagonalization technique. By comparing with the corresponding 1D Hubbard model
      results and by using heuristic arguments we conclude that it is unlikely that
      there is a 2D metal-insulator quantum phase transition, although the effect of
      interaction in some range of parameters is to substantially enhance the
      noninteracting charge stiffness.

PMID- 11289937
TI  - Scattering theory of Kondo mirages and observation of single Kondo atom phase
      shift.
AB  - We explain the origin of the Kondo mirage seen in recent quantum corral scanning
      tunneling microscope experiments with a scattering theory of electrons on the
      surfaces of metals. Our theory, combined with experimental data, provides a
      direct observation of a single Kondo atom phase shift. The Kondo mirage observed
      at the empty focus of an elliptical quantum corral is shown to arise from
      multiple electron bounces off the corral wall adatoms. We demonstrate our theory
      with direct quantitive comparison to experimental data.

PMID- 11289938
TI  - Influence of impurities on localized transition metal surface states: scanning
      tunneling spectroscopy on V(001).
AB  - The first scanning tunneling spectroscopy measurements on V(001) are reported. A
      strong surface state is detected which is very sensitive to the presence of
      segregated carbon impurities. The surface state energy shifts from 0.03 eV below
      the Fermi level at clean areas towards higher energies (up to approximately 0.2
      eV) at contaminated areas. Because of the negative dispersion of this state, the
      upward shift cannot be described in a simple confinement picture. Rather, the
      surface state energy is governed by vanadium surface s- d interactions which are
      altered by carbon coverage.

PMID- 11289939
TI  - Electron energy relaxation in the presence of magnetic impurities.
AB  - We study inelastic electron-electron scattering mediated by the exchange
      interaction of electrons with magnetic impurities and find the kernel of the
      corresponding two-particle collision integral. In a wide region of parameters,
      the kernel K is proportional to the inverse square of the transferred energy, K
      proportional to J4/E2. The exchange constant J is renormalized due to the Kondo
      effect. At small energy transfers, the 1/E2 divergence is cut off; the cutoff
      energy is determined by the dynamics of the impurity spins. The obtained results
      may provide a quantitative explanation of the experiments of Pothier et al.
      [Phys. Rev. Lett. 79, 3490 (1997)] on anomalously strong energy relaxation in
      short metallic wires.

PMID- 11289940
TI  - Optical detection of ballistic electrons injected by a scanning-tunneling
      microscope.
AB  - We demonstrate a spectroscopic technique which is based on ballistic injection of
      minority carriers from the tip of a scanning-tunneling microscope into a
      semiconductor heterostructure. By analyzing the resulting electroluminescence
      spectrum as a function of tip-sample bias, both the injection barrier height and
      the carrier scattering rate in the semiconductor can be determined. This
      technique is complementary to ballistic electron emission spectroscopy since
      minority instead of majority carriers are injected, which give the opportunity to
      study the carrier trajectory after injection.

PMID- 11289941
TI  - Enhancement of tunneling from a correlated 2D electron system by a many-electron
      Mossbauer-type recoil in a magnetic field.
AB  - We consider the effect of electron correlations on tunneling from a 2D electron
      layer in a magnetic field parallel to the layer. A tunneling electron can
      exchange its momentum with other electrons, which leads to an exponential
      increase of the tunneling rate compared to the single-electron approximation. The
      effect depends on the interrelation between the dynamics of tunneling and
      momentum exchange. The results explain and provide a no-parameter fit to the data
      on electrons on helium. We also discuss tunneling in semiconductor
      heterostructures.

PMID- 11289942
TI  - Ising ferromagnetism and domain morphology in the fractional quantum Hall regime.
AB  - The density driven quantum phase transition between the unpolarized and fully
      spin polarized nu = 2/3 fractional quantum Hall state is accompanied by
      hysteresis in accord with 2D Ising ferromagnetism and domain formation. The
      temporal behavior is reminiscent of the Barkhausen and time-logarithmic magnetic
      after-effects ubiquitous in familiar ferromagnets. It too suggests domain
      morphology and, in conjunction with NMR, intricate domain dynamics, which is
      partly mediated by the contact hyperfine interaction with nuclear spins of the
      host semiconductor.

PMID- 11289943
TI  - Superconductivity in ropes of single-walled carbon nanotubes.
AB  - We report measurements on ropes of single-walled carbon nanotubes (SWNT) in low
      resistance contact to nonsuperconducting (normal) metallic pads, at low voltage
      and at temperatures down to 70 mK. In one sample, we find a 2 orders of magnitude
      resistance drop below 0.55 K, which is destroyed by a magnetic field of the order
      of 1 T, or by a dc current greater than 2.5 microA. These features strongly
      suggest the existence of superconductivity in ropes of SWNT.

PMID- 11289944
TI  - Thermodynamic and transport properties of superconducting Mg10B2.
AB  - Transport and thermodynamic properties of a sintered pellet of the newly
      discovered MgB2 superconductor have been measured to determine the characteristic
      critical magnetic fields and critical current densities. Both resistive
      transition and magnetization data give similar values of the upper critical
      field, Hc2, with magnetization data giving dHc2/dT = 0.44 T/K at the transition
      temperature of Tc = 40.2 K. Close to the transition temperature, magnetization
      curves are thermodynamically reversible, but at low temperatures the trapped flux
      can be on the order of 1 T. The value of dHc/dT at Tc is estimated to be about 12
      mT/K, a value similar to classical superconductors like Sn. Hence, the Ginzburg
      Landau parameter kappa approximately 26. Estimates of the critical supercurrent
      density, Jc, using hysteresis loops and the Bean model, give critical current
      densities on the order of 10(5) A/cm2. Hence the supercurrent coupling through
      the grain boundaries is comparable to intermetallics like Nb3Sn.

PMID- 11289945
TI  - Superconductivity in dense MgB2 wires.
AB  - MgB2 becomes superconducting just below 40 K. Whereas porous polycrystalline
      samples of MgB2 can be synthesized from boron powders, in this Letter we
      demonstrate that dense wires of MgB2 can be prepared by exposing boron filaments
      to Mg vapor. The resulting wires have a diameter of 160 microm, are better than
      80% dense, and manifest the full chi = -1/4pi shielding in the superconducting
      state. Temperature-dependent resistivity measurements indicate that MgB2 is a
      highly conducting metal in the normal state with rho(40 K) = 0.38 microOmega cm.
      By using this value, an electronic mean-free path, l approximately 600 A can be
      estimated, indicating that MgB2 wires are well within the clean limit. Tc,
      Hc2(T), and Jc data indicate that MgB2 manifests comparable or better
      superconducting properties in dense wire form than it manifests as a sintered
      pellet.

PMID- 11289946
TI  - Coupling of two superconductors through a ferromagnet: evidence for a pi
      junction.
AB  - We report measurements of the temperature dependence of the critical current,
      I(c), in Josephson junctions consisting of conventional superconducting banks of
      Nb and a weakly ferromagnetic interlayer of a CuxNi1-x alloy, with x around 0.5.
      With decreasing temperature I(c) generally increases, but for specific
      thicknesses of the ferromagnetic interlayer, a maximum is found followed by a
      strong decrease down to zero, after which I(c) rises again. Such a sharp cusp can
      be explained only by assuming that the junction changes from a 0-phase state at
      high temperatures to a pi phase state at low temperatures.

PMID- 11289947
TI  - Depinning of a metastable disordered vortex lattice.
AB  - We report on experiments investigating the depinning dynamics of a strongly
      pinned vortex lattice in 2H-NbSe2. We find that the depinning process starts at
      currents that are well below the critical current of the entire lattice and that
      it is governed by the formation of contiguous channels of mobile vortices
      connecting the sample edges. We obtain the formation time of the first channel by
      monitoring the delayed voltage response to a driving current step and by
      measuring the ramping rate dependence of the critical current. The subsequent
      increase in the number of moving vortices is determined from the temporal
      evolution of the voltage response and the critical current.

PMID- 11289948
TI  - Cu valency change induced by O doping in YBCPO.
AB  - An ab initio local spin density study of YBa2Cu3O6, YBa2Cu3O6.5, and YBa2Cu3O7 is
      presented. The method includes self-interaction corrections for the Cu d states,
      which enables a description of various valency configurations of both planar and
      chain Cu atoms. For YBa2Cu3O6 the antiferromagnetic and insulating state is
      described with planar (chain) Cu occurring in a divalent (trivalent) state. The
      evolution in the CuO2 plane from insulating to metallic behavior upon oxygenation
      is accomplished by the delocalization of the majority Cu d(x2-y2)-O2 p(x)-O3 p(y)
      band.

PMID- 11289949
TI  - Staggered field effect on the one-dimensional S = 1/2 antiferromagnet Yb4As3.
AB  - Inelastic neutron scattering measurements of magnetic excitations in the charge
      ordered state of Yb4As3 have been performed under magnetic field up to about 6 T.
      By applying a magnetic field, the spectrum at the one-dimensional wave vector q =
      1 [ pi/d] changes drastically from a broad one corresponding to the spinon
      excitation continuum of the one-dimensional S = 1 / 2 spin system to a sharp one
      at a finite energy, indicating the opening of an energy gap in the system. The
      magnetic field dependence of the gap is well fitted by the power law H2/3. The
      experimental result gives strong evidence for the existence of a staggered field
      alternating along Yb3+ chains induced by the Dzyaloshinsky-Moriya interaction.

PMID- 11289950
TI  - Finding universal correlations between cationic disorder and low field
      magnetoresistance in FeMo double perovskite series.
AB  - We search for general patterns that explain the low field magnetoresistance at
      low temperatures in the system A(2-x)A'xFeMoO6. The observed linear dependence of
      the low field magnetoresistance with the saturation magnetization for the series
      is related to the antisite disorder at the Fe and Mo sites. This is explained in
      terms of a spin dependent crossing of intragranular barriers originated from the
      presence of antiferromagnetic SrFeO3 patches that naturally develop when antisite
      disorder occurs in the double perovskite. The presence of a moderate level of
      antisite disorder is at the very root of low field magnetoresistance although
      effects such as disorder distribution, connectivity, or morphology add their
      contribution.

PMID- 11289951
TI  - Quantum frustration in the "spin liquid" phase of two-dimensional 3He.
AB  - We have measured the ultralow temperature and low field magnetic susceptibility
      of the 4/7 phase of two-dimensional 3He adsorbed on graphite preplated by one
      layer of 4He. The experiments are performed by progressively adding 4He to the
      system, thus suppressing in a controlled way the 3He atoms trapped in substrate
      heterogeneities. This procedure enables us to determine the intrinsic properties
      of this spin 1/2 model magnet in the zero field limit. The results show
      quantitatively that the system is strongly frustrated by multiple spin exchange
      interactions. A characteristic gapped spin liquid behavior is observed at
      ultralow temperature.

PMID- 11289952
TI  - Quantum-kinetic theory of hot luminescence from pulse-excited semiconductors.
AB  - A theory of time-resolved luminescence from photoexcited semiconductors is
      presented. It combines quantum kinetics of hot-carrier relaxation and quantum
      theory of spontaneous emission. Model calculations show the "transfer" of
      photoluminescence from the initial signal at the pump frequency via subsequent
      phonon replicas until the buildup of luminescence at the excitonic resonance.
      Time-resolved photoluminescence is predicted to be a sensitive measure of
      electron-LO-phonon quantum kinetics and bottleneck effects.

PMID- 11289953
TI  - Master equation for retrodiction of quantum communication signals.
AB  - We derive the master equation that governs the evolution of the measured state
      backwards in time in an open system. This allows us to determine probabilities
      for a given set of preparation events from the results of subsequent
      measurements, which has particular relevance to quantum communication.

PMID- 11289954
TI  - Transitions induced by the discreteness of molecules in a small autocatalytic
      system.
AB  - The autocatalytic reaction system with a small number of molecules is studied
      numerically by stochastic particle simulations. A novel state due to fluctuation
      and discreteness in molecular numbers is found, characterized as an extinction of
      molecule species alternately in the autocatalytic reaction loop. Phase transition
      to this state with changes of the system size and flow is studied, while a single
      molecule switch of the molecule distributions is reported. The relevance of the
      results to intracellular processes is briefly discussed.

PMID- 11289955
TI  - Green's function approach to nonclassical reaction kinetics in fractal media.
AB  - We present an accurate description for the mean field kinetics of the reversible
      recombination reaction occurring in fractal media, which is in good agreement
      with Monte Carlo simulation results from an intermediate to a long time region.
      The central dynamic quantity is the Green's function for the generalized
      diffusion equation that is defined in a hypothetical space whose dimensionality
      is given by the fracton dimension d. An exact expression for the Green's function
      that is valid for arbitrary values of d is presented.

PMID- 11289956
TI  - Molecular dynamics simulation of continuous current flow through a model
      biological membrane channel.
AB  - The conductance of sodium ions through a simplified channel-membrane system
      immersed in a reservoir of 1M NaCl in SPC/E water is examined by molecular
      dynamics simulation. An applied external potential of 1.1 V drives the ions and
      water through a channel of length 25 A producing a current of 19.6 pA, in
      reasonable agreement with experimental findings. The stream of ions and water
      molecules flows continuously because of the constant applied field and periodic
      boundary conditions. We also examine the potential profile across the simulation
      cell, the average density distributions of the various species in the reservoir
      and radially in the channel, and the ion velocity in the channel.

PMID- 11289957
TI  - Long-range correlations in genomic DNA: a signature of the nucleosomal structure.
AB  - We use the "wavelet transform microscope" to carry out a comparative statistical
      analysis of DNA bending profiles and of the corresponding DNA texts. In the three
      kingdoms, one reveals on both signals a characteristic scale of 100-200 bp that
      separates two different regimes of power-law correlations (PLC). In the small
      scale regime, PLC are observed in eukaryotic, in double-strand DNA viral, and in
      archaeal genomes, which contrasts with their total absence in the genomes of
      eubacteria and their viruses. This strongly suggests that small-scale PLC are
      related to the mechanisms underlying the wrapping of DNA in the nucleosomal
      structure. We further speculate that the large scale PLC are the signature of the
      higher-order structure and dynamics of chromatin.

PMID- 11289958
TI  - Solitons in the one-dimensional forest fire model.
AB  - Fires in the one-dimensional Bak-Chen-Tang forest fire model propagate as
      solitons, resembling shocks in Burgers turbulence. The branching of solitons,
      creating new fires, is balanced by the pairwise annihilation of oppositely moving
      solitons. Two distinct, diverging length scales appear in the limit where the
      growth rate of trees, p, vanishes. The width of the solitons, w, diverges as a
      power law, 1/p, while the average distance between solitons diverges much faster
      as d approximately exp(pi2/12p).

PMID- 11289959
TI  - Comment on "charge-orbital stripe structure in La1-xCaxMnO3 ( x = 1/2, 2/3)".

PMID- 11289961
TI  - Comment on "low temperature acoustic properties of amorphous silica and the
      tunneling model".

PMID- 11289963
TI  - Shape of the quantum diffusion front.
AB  - We show that quantum diffusion has well-defined front shape. After an initial
      transient, the wave packet front (tails) is described by a stretched exponential
      P(x,t) = A(t)exp(-absolute value of [x/w](gamma)), with 1 < gamma < infinity,
      where w(t) is the spreading width which scales as w(t) approximately t(beta),
      with 0 < beta < or = 1. The two exponents satisfy the universal relation gamma =
      1/(1-beta). We demonstrate these results through numerical work on one
      dimensional quasiperiodic systems and the three-dimensional Anderson model of
      disorder. We provide an analytical derivation of these relations by using the
      memory function formalism of quantum dynamics. Furthermore, we present an
      application to experimental results for the quantum kicked rotor.

PMID- 11289964
TI  - Environment-independent decoherence rate in classically chaotic systems.
AB  - We study the decoherence of a one-particle system, whose classical correspondent
      is chaotic, when it evolves coupled to a weak quenched environment. This is done
      by analytical evaluation of the Loschmidt echo (i.e., the revival of a localized
      density excitation upon reversal of its time evolution), in the presence of the
      perturbation. We predict an exponential decay for the Loschmidt echo with a
      (decoherence) rate which is asymptotically given by the mean Lyapunov exponent of
      the classical system, and therefore independent of the perturbation strength,
      within a given range of strengths. Our results are consistent with recent
      experiments of polarization echoes in nuclear magnetic resonance and numerical
      simulations.

PMID- 11289965
TI  - Ballistic annihilation with continuous isotropic initial velocity distribution.
AB  - Ballistic annihilation with continuous initial velocity distributions is
      investigated in the framework of the Boltzmann equation. The particle density and
      the rms velocity decay as c approximately t(-alpha) and velocity approximately t(
      beta), with the exponents depending on the initial velocity distribution and the
      spatial dimension d. For instance, in one dimension for the uniform initial
      velocity distribution beta = 0.230 472ellipsis. In the opposite extreme d-
      >infinity, the dynamics is universal and beta-->(1-2(-1/2))d(-1). We also solve
      the Boltzmann equation for Maxwell particles and very hard particles in arbitrary
      spatial dimension. These solvable cases provide bounds for the decay exponents of
      the hard sphere gas.

PMID- 11289966
TI  - Boundary induced phase transitions in driven lattice gases with metastable
      states.
AB  - We study the effect of metastability onto boundary induced phase transitions in a
      driven lattice gas. The phase diagram for open systems, parameterized by the
      input and output rates, consists of two regions corresponding to the free flow
      and jammed phase. Both have been entirely characterized. The microscopic states
      in the high density phase are shown to have an interesting striped structure,
      which undergoes a coarsening process and survives in the thermodynamic limit.

PMID- 11289967
TI  - Naturally small seesaw neutrino mass with no new physics beyond the TeV scale.
AB  - If there is no new physics beyond the TeV energy scale, such as in a theory of
      large extra dimensions, the smallness of the seesaw neutrino mass, i.e., m(nu) =
      m(2)(D)/m(N), cannot be explained by a very large m(N). In contrast to previous
      attempts to find an alternative mechanism for a small m(nu), I show how a
      solution may be obtained in a simple extension of the standard model, without
      using any ingredient supplied by the large extra dimensions. It is also
      experimentally testable at future accelerators.

PMID- 11289968
TI  - New limit on the permanent electric dipole moment of 199Hg.
AB  - We present the first results of a new search for a permanent electric dipole
      moment of the 199Hg atom using a UV laser. Our measurements give d(199Hg) = 
      (1.06+/-0.49+/-0.40)x10(-28)e cm. We interpret the result as an upper limit
      absolute value [d(199Hg)]<2.1x10(-28)e cm (95% C.L.), which sets new constraints
      on theta bar;(QCD), chromo-EDMs of the quarks, and CP violation in supersymmetric
      models.

PMID- 11289972
TI  - Observation of polarization in bottomonium production at square root of s = 38.8
      GeV.
AB  - We present a measurement of the polarization observed for bottomonium states
      produced in p-Cu collisions at square root of s = 38.8 GeV. The angular
      distribution of the decay dimuons of the Upsilon(1S) state shows no polarization
      at small values of the fractional longitudinal momentum x(F) and transverse
      momentum p(T) but significant positive transverse production polarization for
      either p(T)>1.8 GeV/c or for x(F)>0.35. The Upsilon(2S+3S) (unresolved) states
      show a large transverse production polarization at all values of x(F) and p(T)
      measured. These observations challenge NRQCD calculations of the polarization
      expected in the hadronic production of bottomonium states.

PMID- 11289969
TI  - Measurement of the CP violation parameter sin2 phi(1) in B(0)(d) meson decays.
AB  - We present a measurement of the standard model CP violation parameter sin2 phi(1)
      (also known as sin2beta) based on a 10.5 fb(-1) data sample collected at the
      Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-)
      collider. One neutral B meson is reconstructed in the J/psiK(S), psi(2S)K(S),
      chi(c1)K(S), eta(c)K(S), J/psiK(L), or J/psipi(0) CP-eigenstate decay channel and
      the flavor of the accompanying B meson is identified from its charged particle
      decay products. From the asymmetry in the distribution of the time interval
      between the two B-meson decay points, we determine sin2 phi(1) = 0.58(+0.32)(
      0.34)(stat)+0.09-0.10(syst).

PMID- 11289974
TI  - High p(T) azimuthal asymmetry in noncentral A + A at RHIC.
AB  - The high p(T)>3 GeV azimuthal asymmetry, v(2)(p(T)), in noncentral nuclear
      collisions at RHIC is shown to be a sensitive measure of the initial parton
      density distribution of the produced quark-gluon plasma. A generalization of the
      Gyulassy-Levai-Vitev non-Abelian energy loss formalism including Bjorken (1+1)D
      expansion as well as important kinematic constraints is used.

PMID- 11289975
TI  - Counterintuitive alignment of H2(+) in intense femtosecond laser fields.
AB  - The multiphoton ionization of H2 has been studied using laser pulses of 266 nm
      wavelength, 250 fs duration, and 5x10(13) W/cm(2) peak intensity. Dissociation of
      H2(+) via one-photon absorption proceeds through two channels with markedly
      different proton angular distributions. The lower-energy channel (2.6 eV kinetic
      energy release) is produced in the bond softening mechanism, which generates
      parallel alignment. The higher-energy channel (3.5 eV) originates from population
      trapping in a light-induced bound state, where bond hardening generates
      orthogonal, counterintuitive alignment.

PMID- 11289973
TI  - Directed flow of lambda hyperons in (2-6 )A GeV Au+Au collisions.
AB  - Directed flow measurements for Lambda hyperons are presented and compared to
      those for protons produced in the same Au+Au collisions (2A, 4A, and 6A GeV; b<5
      6 fm). The measurements indicate that Lambda hyperons flow consistently in the
      same direction but with smaller magnitudes. A strong positive flow [for Lambdas]
      has been predicted in calculations which include the influence of the Lambda
      nucleon potential. The experimental flow ratio Lambda/p is in qualitative
      agreement with expectations (approximately 2/3) from the quark counting rule at
      2A GeV but is found to decrease with increasing beam energy.

PMID- 11289976
TI  - Structure and magnetism of neutral and anionic palladium clusters.
AB  - The properties of neutral and anionic Pd(N) clusters were investigated with spin
      density-functional calculations. The ground-state structures are three
      dimensional for N>3 and they are magnetic with a spin triplet for 2 < or = N < or
      = 7 and a spin nonet for N = 13 neutral clusters. Structural and spin isomers
      were determined and an anomalous increase of the magnetic moment with temperature
      is predicted for a Pd7 ensemble. Vertical electron detachment and ionization
      energies were calculated and the former agrees well with measured values for Pd(
      )(N).

PMID- 11289977
TI  - Fresnel light drag in a coherently driven moving medium.
AB  - We theoretically study how the phase of a light plane wave propagating in a
      resonant medium under electromagnetically induced transparency (EIT) is affected
      by the uniform motion of the medium. For cuprous oxide (Cu2O), where EIT can be
      implemented through a typical pump-probe configuration, the resonant probe beam
      experiences a phase shift (Fresnel-Fizeau effect) that may vary over a wide range
      of values, positive or negative, and even vanishing, due to the combined effects
      of the strong frequency dispersion and anisotropy both induced by the pump. The
      use of such a coherently driven dragging medium may improve by at least 1 order
      of magnitude the sensitivity at low velocity in optical drag experiments.

PMID- 11289978
TI  - Grazing and border-collision in piecewise-smooth systems: a unified analytical
      framework.
AB  - A comprehensive derivation is presented of normal form maps for grazing
      bifurcations in piecewise smooth models of physical processes. This links
      grazings with border-collisions in nonsmooth maps. Contrary to previous
      literature, piecewise linear maps correspond only to nonsmooth discontinuity
      boundaries. All other maps have either square-root or (3/2)-type singularities.

PMID- 11289979
TI  - Onset of wave drag due to generation of capillary-gravity waves by a moving
      object as a critical phenomenon.
AB  - The onset of the wave resistance, via generation of capillary-gravity waves of a
      small object moving with velocity V, is investigated experimentally. Because of
      the existence of a minimum phase velocity V(c) for surface waves, the problem is
      similar to the generation of rotons in superfluid helium near their minimum. In
      both cases waves or rotons are produced at V>V(c) due to Cherenkov radiation. We
      find that the transition to the wave drag state is continuous: in the vicinity of
      the bifurcation the wave resistance force is proportional to sqrt[V-V(c)] for
      various fluids.

PMID- 11289980
TI  - Superradiant and stimulated superradiant emission in a prebunched beam free
      electron maser.
AB  - An electron beam, prebunched at the synchronous free-electron laser frequency and
      passing through a magnetic undulator, emits coherent (superradiant) synchrotron
      undulator radiation at the bunching frequency. If an external electromagnetic
      wave is introduced into the interaction region, at the same frequency and at a
      proper phase, the radiation process will be stimulated (stimulated prebunched
      beam radiation). We report first experimental measurements of stimulated
      superradiant emission in a prebunched free-electron maser. Measurements are in
      good agreement with theory.

PMID- 11289982
TI  - Longitudinal and transverse waves in Yukawa crystals.
AB  - A unified theoretical treatment is given of longitudinal (or compressional) and
      transverse modes in Yukawa crystals, including the effects of damping. Dispersion
      relations are obtained for hexagonal lattices in two dimensions and bcc and fcc
      lattices in three dimensions. Theoretical predictions are compared with two
      recent experiments.

PMID- 11289981
TI  - Thomson scattering measurements of saturated ion waves in laser fusion plasmas.
AB  - We have measured the characteristics of saturated ion-acoustic waves in inertial
      confinement fusion plasmas. A 263-nm probe laser has been applied to simultaneous
      Thomson scatter on both ion-acoustic waves excited by thermal electrostatic
      fluctuations and by stimulated Brillouin scattering of a kilojoule laser beam of
      varying intensity. The Thomson scattering spectra show saturated ion-wave
      amplitudes for intensities above 5x10(14) W cm(-2) consistent with three
      dimensional nonlinear wave modeling.

PMID- 11289983
TI  - Critical-point phase separation in laser ablation of conductors.
AB  - Laser ablation due to an ultrashort laser pulse on a massive aluminum target was
      investigated by means of a one-dimensional fluid code. Clear separation between
      the ablated matter and the unablated target is seen to occur through spinodal
      decomposition involving thermodynamic instabilities near the critical point of
      aluminum. The code also shows that the end of the ablation process is preceded by
      the ejection of droplets, which form about 15% of the total ejected mass.

PMID- 11289984
TI  - Anomalous capillary length in cellular nematic-isotropic interfaces.
AB  - The long-standing puzzle of why capillary lengths measured in cellular nematic
      isotropic interfaces are much longer than the value of 0.05 A predicted by
      Mullins-Sekerka theory has been solved. The resolution of the paradox is that in
      confined systems the substrate-nematic anchoring energy contributes to the
      capillary length which is greatly increased by selective adsorption of ions on
      the substrate.

PMID- 11289985
TI  - Thermodynamic suppression of Brownian motion.
AB  - We have used helium-3 nuclear reaction analysis to measure the Brownian motion
      (intradiffusion coefficient) of polystyrene in a partially miscible blend with
      poly(alpha-methylstyrene). In the one-phase region, when the correlation length
      is close to the polystyrene chain size, the intradiffusion coefficient falls to
      half of its thermal value. For larger and smaller values of the correlation
      length, diffusion is normal. These results show that the correlation length of a
      polymer blend constrains polymer diffusion, as suggested from previous neutron
      scattering measurements, and mean-field theory.

PMID- 11289987
TI  - Step edge diffusion and step atom detachment in surface evolution: ion erosion of
      Pt(111).
AB  - The temperature dependent morphological evolution of Pt(111) under 1 keV Xe+
      normal incidence ion bombardment has been investigated up to 600 monolayers
      removed. Coarsening of the surface structures during erosion and a qualitative
      change in roughness evolution between 650 and 700 K are found to be caused by
      different atomic processes: the former by diffusion of atoms along steps, the
      latter by the onset of step atom detachment.

PMID- 11289986
TI  - Quenched Kosterlitz-Thouless superfluid transitions.
AB  - Rapidly quenched Kosterlitz-Thouless (KT) superfluid transitions are studied by
      solving the Fokker-Planck equation for the vortex-pair dynamics in conjunction
      with the KT recursion relations. Power-law decays of the vortex density at long
      times are found, and the results are in agreement with a scaling proposal made by
      Minnhagen and co-workers for the dynamical critical exponent. The superfluid
      density is strongly depressed after a quench, with the subsequent recovery being
      logarithmically slow for starting temperatures near T(KT). No evidence is found
      of vortices being "created" in a rapid quench; there is only decay of the
      existing thermal vortex pairs.

PMID- 11289988
TI  - Symmetry selection rules for vibrationally inelastic tunneling.
AB  - A combined experimental and theoretical study is presented for the C-D stretch
      mode excitation of acetylene isotopes, C2HD and C2D2, on Cu(100) via inelastic
      electron tunneling (IET) in a scanning tunneling microscope junction. The
      calculated IET images using density functional theory show that the measured
      signal from C2D2 derives from the antisymmetric stretch mode. Selection rules are
      derived and involve the constraint imposed by the IET image on the symmetry
      characters of the vibrational mode and the adsorbate-induced electron states at
      the Fermi level.

PMID- 11289971
TI  - Ratio of jet cross sections at square root of s = 630 GeV and 1800 GeV.
AB  - The D0 Collaboration has measured the inclusive jet cross section in barpp
      collisions at square root of s = 630 GeV. The results for pseudorapidities
      (eta)<0.5 are combined with our previous results at square root of s = 1800 GeV
      to form a ratio of cross sections with smaller uncertainties than either
      individual measurement. Next-to-leading-order QCD predictions show excellent
      agreement with the measurement at 630 GeV; agreement is also satisfactory for the
      ratio. Specifically, despite a 10% to 15% difference in the absolute magnitude,
      the dependence of the ratio on jet transverse momentum is very similar for data
      and theory.

PMID- 11289989
TI  - Dynamic force spectroscopy of conservative and dissipative forces in an Al
      Au(111) tip-sample system.
AB  - The conservative and dissipative interaction between an aluminum tip and a gold
      (111) surface were investigated using dynamic force spectroscopy in UHV. Complete
      force vs distance curves and friction coefficient vs distance curves were
      obtained quantitatively. The force curves were compared to the model by Muller,
      Yushenko, and Derjaguin, and long and short range interactions were subsequently
      quantified without fit parameters. A short range conservative interaction was
      separated from longer range van der Waals forces. The long range behavior of the
      damping coefficient obeys an inverse power law of third order.

PMID- 11289990
TI  - Experimental confirmation of the predicted shallow donor hydrogen state in zinc
      oxide.
AB  - We confirm the recent prediction that interstitial protium may act as a shallow
      donor in zinc oxide, by direct spectroscopic observation of its muonium
      counterpart. On implantation into ZnO, positive muons--chemically analogous to
      protons in this context--form paramagnetic centers below about 40 K. The muon
      electron contact hyperfine interaction, as well as the temperature and activation
      energy for ionization, imply a shallow level. Similar results for the cadmium
      chalcogenides suggest that such shallow donor states are generic to the II-VI
      compounds. The donor level depths should serve as a guide for the electrical
      activity of interstitial hydrogen.

PMID- 11289991
TI  - Time-dependent Gutzwiller approximation for the Hubbard model.
AB  - We develop a time-dependent Gutzwiller approximation (GA) for the Hubbard model
      analogous to the time-dependent Hartree-Fock (HF) method. This new formalism
      incorporates ground state correlations of the random phase approximation (RPA)
      type beyond the GA. Static quantities like ground state energy and double
      occupancy are in excellent agreement with exact results in one dimension up to
      moderate coupling and in two dimensions for all couplings. We find a substantial
      improvement over traditional GA and HF+RPA treatments. Dynamical correlation
      functions can be computed and are also substantially better than HF+RPA ones and
      obey well behaved sum rules.

PMID- 11289992
TI  - Spatial correlations in GaInAsN alloys and their effects on band-gap enhancement
      and electron localization.
AB  - In contrast to pseudobinary alloys, the relative number of bonds in quaternary
      alloys cannot be determined uniquely from the composition. Indeed, we do not know
      if the Ga0.5In0.5As0.5N0.5 alloy should be thought of as InAs+GaN or as InN+GaAs.
      We study the distribution of bonds using Monte Carlo simulation and find that the
      number of In-N and Ga-As bonds increases relative to random alloys. This
      quaternary-unique short range order affects the band structure: we calculate a
      blueshift of the band gap and predict the emergence of a broadband tail of
      localized states around the conduction band minimum.

PMID- 11289993
TI  - Evolution of III-V nitride alloy electronic structure: the localized to
      delocalized transition.
AB  - Addition of nitrogen to III-V semiconductor alloys radically changes their
      electronic properties. We report large-scale electronic structure calculations of
      GaAsN and GaPN using an approach that allows arbitrary states to emerge, couple,
      and evolve with composition. We find a novel mechanism of alloy formation where
      localized cluster states within the gap are gradually overtaken by a downwards
      moving conduction band edge, composed of both localized and delocalized states.
      This localized to delocalized transition explains many of the hitherto puzzling
      experimentally observed anomalies in III-V nitride alloys.

PMID- 11289994
TI  - Spin orthogonality catastrophe in two-dimensional antiferromagnets and
      superconductors.
AB  - We compute the spectral function of a spin S hole injected into a two-dimensional
      antiferromagnet or superconductor in the vicinity of a magnetic quantum critical
      point. We show that, near Van Hove singularities, the problem maps onto that of a
      static vacancy carrying excess spin S. The hole creation operator is
      characterized by a new boundary anomalous dimension and a vanishing quasiparticle
      residue at the critical point. We discuss possible relevance to photoemission
      spectra of cuprate superconductors near the antinodal points.

PMID- 11289995
TI  - Exactly solvable model with two conductor-insulator transitions driven by
      impurities.
AB  - We present an exact analysis of two conductor-insulator transitions in the random
      graph model where low connectivity means high impurity concentration. The
      adjacency matrix of the random graph is used as a hopping Hamiltonian. We compute
      the height of the delta peak at zero energy in its spectrum exactly and describe
      analytically the structure and contribution of localized eigenvectors. The system
      is a conductor for average connectivities between 1.421 529ellipsis and 3.154
      985ellipsis but an insulator in the other regimes. We explain the spectral
      singularity at average connectivity e = 2.718 281ellipsis and relate it to other
      enumerative problems in random graph theory.

PMID- 11289996
TI  - Novel metallic behavior in two dimensions.
AB  - Experiments on a sufficiently disordered two-dimensional (2D) electron system in
      silicon reveal a new and unexpected kind of metallic behavior, where the
      conductivity decreases as sigma(n(s),T) = sigma(n(s),T = 0)+A(n(s))T(2) (where
      n(s) is carrier density) to a nonzero value as temperature T-->0. In 2D, the
      existence of a metal with dsigma/dT>0 is very surprising. In addition, a novel
      type of a metal-insulator transition obtains, which is unlike any known quantum
      phase transition in 2D.

PMID- 11289997
TI  - Kondo temperature for the two-channel Kondo models of tunneling centers.
AB  - A two-channel Kondo (2CK) non-Fermi liquid state in a metal resulting from the
      interaction between electrons and structural defects modeled by double-well
      potentials (DWP) is revisited. Account only of the two lowest states in DWP is
      known to lead to rather low Kondo temperature, T(K). We prove that the
      contribution of higher excited states reduces T(K), if all of the intermediate
      states are taken into account. Prefactor in T(K) is shown to be determined by the
      spacing between the second and the third levels epsilon(3) in DWP rather than by
      the electron Fermi energy epsilon(F). Since epsilon(3)<<epsilon(F) there is no
      microscopic model of movable defects which may justify 2CK phenomenology.

PMID- 11289998
TI  - Electronic structure of partially hydrogenated Si(100)-( 2 x 1) surfaces prepared
      by thermal and nonthermal desorption.
AB  - The electronic structure of partially hydrogenated Si(100)- (2 x 1) surfaces,
      prepared by controlled thermal annealing and nonthermal photon stimulated
      desorption of fully hydrogenated Si(100) surfaces, has been investigated by using
      valence band photoemission. Thermal and nonthermal desorption are found to
      produce very specific electronic surface structures. This led us to the discovery
      of two specific surface states having binding energies of 1.0 and 0.7 eV
      associated with the isolated Si dimers and single Si dangling bonds,
      respectively.

PMID- 11289999
TI  - Observation of multiple magnetorotons in the fractional quantum Hall effect.
AB  - Magnetorotons in the dispersions of collective gap excitation modes of fractional
      quantum Hall liquids are measured in resonant inelastic light scattering
      experiments. Two deep magnetoroton minima are observed at nu = 2/5, while a
      single deep minimum is resolved at nu = 1/3. The observations are the first
      evidence of multiple roton minima in gap excitations of the quantum liquids. The
      results support Chern-Simons and composite fermion calculations that predict
      multiple roton minima for states with nu>1/3.

PMID- 11290000
TI  - Strong linear- k valence-band mixing at semiconductor heterojunctions.
AB  - This paper examines linear- k terms in the gamma(8) valence-band Hamiltonian for
      heterostructures of zinc-blende-type semiconductors. In bulk crystals such terms
      are known to be extremely small, due to their origin as relativistic
      perturbations from d and f orbitals. However, in heterostructures there is a
      nonvanishing contribution from p orbitals. This contribution is an order of
      magnitude larger than the corresponding bulk term, and it should give rise to an
      optical anisotropy comparable to (although smaller than) that seen in recent
      experiments on the quantum-well Pockels effect.

PMID- 11290001
TI  - Resonant tunneling into a biased fractional quantum Hall edge.
AB  - We observe resonant tunneling into a voltage biased fractional quantum Hall
      effect (FQHE) edge, using atomically sharp tunnel barriers unique to cleaved-edge
      overgrown devices. The resonances demonstrate different tunnel couplings to the
      metallic lead and the FQHE edge. Weak coupling to the FQHE edge produces clear
      non-Fermi liquid behavior with a sixfold increase in resonance area under bias
      arising from the power law density of states at the FQHE edge. A simple device
      model uses the resonant tunneling formalism for chiral Luttinger liquids to
      successfully describe the data.

PMID- 11289970
TI  - Measurement of CP-violating asymmetries in B0 decays to CP eigenstates.
AB  - We present measurements of time-dependent CP-violating asymmetries in neutral B
      decays to several CP eigenstates. The measurement uses a data sample of 23x10(6)
      Upsilon(4S)-->BbarB decays collected by the BABAR detector at the PEP-II
      asymmetric B Factory at SLAC. In this sample, we find events in which one neutral
      B meson is fully reconstructed in a CP eigenstate containing charmonium and the
      flavor of the other neutral B meson is determined from its decay products. The
      amplitude of the CP-violating asymmetry, which in the standard model is
      proportional to sin2beta, is derived from the decay time distributions in such
      events. The result is sin2beta = 0.34+/-0.20 (stat)+/-0.05 (syst).

PMID- 11290002
TI  - Anisotropy of magnetothermal conductivity in Sr2RuO4.
AB  - The dependence of in-plane and interplane thermal conductivities of Sr2RuO4 on
      temperature, as well as magnetic field strength and orientation, is reported. We
      found no notable anisotropy in the thermal conductivity for the magnetic field
      rotation parallel to the conducting plane in the whole range of experimental
      temperatures and fields, except in the vicinity of the upper critical field
      H(c2), where the anisotropy of the H(c2) itself plays a dominant role. This
      finding imposes strong constraints on the possible models of superconductivity in
      Sr2RuO4 and supports the existence of a superconducting gap with a line of nodes
      running orthogonal to the Fermi surface cylinder.

PMID- 11290003
TI  - Superconducting gap structure of spin-triplet superconductor Sr2RuO4 studied by
      thermal conductivity.
AB  - To clarify the superconducting gap structure of the spin-triplet superconductor
      Sr2RuO4, the in-plane thermal conductivity has been measured as a function of
      relative orientations of the thermal flow, the crystal axes, and a magnetic field
      rotating within the 2D RuO2 planes. The in-plane variation of the thermal
      conductivity is incompatible with any model with line nodes vertical to the 2D
      planes and indicates the existence of horizontal nodes. These results place
      strong constraints on models that attempt to explain the mechanism of the triplet
      superconductivity.

PMID- 11290004
TI  - Magnetic field dependence of the superconducting gap and the pseudogap in Bi2212
      and HgBr2-Bi2212, studied by intrinsic tunneling spectroscopy.
AB  - Intrinsic tunneling spectroscopy in high magnetic field (H) is used for a direct
      test of superconducting features in the quasiparticle density of states of pure
      Bi2212 and intercalated HgBr2-Bi2212 high- T(c) superconductors. We were able to
      distinguish with great clarity two coexisting gaps: (i) the superconducting gap,
      which closes as H-->H(c2)(T), and (ii) the c-axis pseudogap, which does not
      change either with H or with T. Strikingly different H dependencies, together
      with previously observed different temperature dependencies of the two gaps,
      speak against a superconducting origin of the pseudogap.

PMID- 11290005
TI  - Metamagnetism and critical fluctuations in high quality single crystals of the
      bilayer ruthenate Sr3Ru2O7.
AB  - We report the results of low temperature transport, specific heat, and
      magnetization measurements on high quality single crystals of the bilayer
      perovskite Sr3Ru2O7, which is a close relative of the unconventional
      superconductor Sr2RuO4. Metamagnetism is observed, and transport and
      thermodynamic evidence for associated critical fluctuations is presented. These
      relatively unusual fluctuations might be pictured as variations in the Fermi
      surface topography itself.

PMID- 11290006
TI  - Thickness-dependent Curie temperatures of ultrathin magnetic films: effect of the
      range of spin-spin interactions.
AB  - We present a simple model of spin-spin coupling which provides insight into the
      nature of the rapid decrease in the Curie temperature with decreasing thin film
      thickness n (number of monolayers). The shift of Curie temperature t(n) = 1
      T(c)(n)/T(c)(infinity) follows the usual power law t(n) approximately n(-lambda)
      in thin films crossing over to linear behavior t(n) approximately n in the
      ultrathin film thickness limit. Experimental results for ferromagnetic thin films
      are compared, and shown to follow curves of t(n) with lambda values dependent on
      the nature of the spin-spin interactions.

PMID- 11290007
TI  - Evidence of laser-wavelength effect in picosecond ultrasonics: possible
      connection with interband transitions.
AB  - We have studied the effect of wavelength change on picosecond acoustic pulses
      generated using a femtosecond laser. For the first time, we show that the pulse
      shape can be strongly influenced by the laser wavelength. The results are in
      excellent agreement with a calculation based on a thermoelastic model which
      connects them to significant changes in the piezo-optical constants. There are
      similarities between the present study and stress modulation spectroscopy, which
      allows us to ascribe the observations to interband transitions and suggests thus
      a new potentiality of picosecond ultrasonics.

PMID- 11290008
TI  - Line emission in single-bubble sonoluminescence.
AB  - We report that single-bubble sonoluminescence (SBSL) at low light intensities
      produces emission bands similar to multibubble sonoluminescence (MBSL) for pure
      noble gas bubbles. A smooth crossover between SBSL and MBSL behavior can be
      induced by varying the acoustic pressure amplitude and thereby the intensity of
      the light emitted. The relative intensity of the band emission depends both on
      the molecular weight of the noble gas and the water temperature. Our results
      provide a connection between the mechanisms SBSL and MBSL and show that molecular
      emission plays a role in SBSL.

PMID- 11290009
TI  - Optical manipulation of nuclear spin by a two-dimensional electron gas.
AB  - Conduction electrons are used to optically polarize, detect, and manipulate
      nuclear spin in a (110) GaAs quantum well. Using optical Larmor magnetometry, we
      find that nuclear spin can be polarized along or against the applied magnetic
      field, depending on field polarity and tilting of the sample with respect to the
      optical pump beam. Periodic optical excitation of the quantum-confined electron
      spin reveals a complete spectrum of optically induced and quadrupolar-split
      nuclear resonances, as well as evidence for Deltam = 2 transitions.

PMID- 11290010
TI  - Nonadditivity of bipartite distillable entanglement follows from a conjecture on
      bound entangled Werner states.
AB  - Assuming the validity of a conjecture given by DiVincenzo et al. [Phys. Rev. A
      61, 062312 (2000)] and by Dur et al. [Phys. Rev. A 61, 062313 (2000)], we show
      that the distillable entanglement for two bipartite states, each of which
      individually has zero distillable entanglement, can be nonzero. We show that this
      also implies that the distillable entanglement is not a convex function. Our
      example consists of the tensor product of a bound entangled state based on an
      unextendible product basis with an entangled Werner state which lies in the class
      of conjectured undistillable states.

PMID- 11290011
TI  - An accurate von Neumann's law for three-dimensional foams.
AB  - The diffusive coarsening of 2D soap froths is governed by von Neumann's law. A
      statistical version of this law for dry 3D foams has long been conjectured. A new
      derivation, based on a theorem by Minkowski, yields an explicit analytical von
      Neumann's law in 3D which is in very good agreement with detailed simulations and
      experiments. The average growth rate of a bubble with F faces is shown to be
      proportional to F1/2 for large F, in contrast to the conjectured linear
      dependence. Accounting for foam disorder in the model further improves the
      agreement with data.

PMID- 11290012
TI  - Self-organized critical drainage networks.
AB  - We introduce time-dependent boundary conditions in a model of drainage network
      evolution based on local erosion rules. The changing boundary conditions prevent
      the model from becoming stationary; it approaches a state where fluctuations of
      all sizes occur. The fluctuations in the sizes of the drainage areas show power
      law behavior with an exponent that differs significantly from that of the static
      distribution of the drainage areas. Thus, the model exhibits self-organized
      criticality and proposes a novel concept for predicting fractal properties of
      drainage networks.

PMID- 11290013
TI  - Comment on "Breakdown of Bohr's correspondence principle".

PMID- 11290014
TI  - Comment on "Breakdown of Bohr's correspondence principle".

PMID- 11290015
TI  - Comment on "Dynamics of surface migration in the weak corrugation regime".

PMID- 11290016
TI  - Comment on "Kinetic roughening in polymer film growth by vapor deposition".

PMID- 11290018
TI  - From the quantum zeno to the inverse quantum zeno effect.
AB  - The temporal evolution of an unstable quantum mechanical system undergoing
      repeated measurements is investigated. In general, by changing the time interval
      between successive measurements, the decay can be accelerated (inverse quantum
      Zeno effect) or slowed down (quantum Zeno effect), depending on the features of
      the interaction Hamiltonian. A geometric criterion is proposed for a transition
      to occur between these two regimes.

PMID- 11290019
TI  - Structure and stability of vortices in dilute Bose-Einstein condensates at
      ultralow temperatures.
AB  - We compute the structure of a quantized vortex line in a harmonically trapped
      dilute atomic Bose-Einstein condensate using the Popov version of the Hartree
      Fock-Bogoliubov mean-field theory. The vortex is shown to be (meta)stable in a
      nonrotating trap even in the zero-temperature limit, thus confirming that weak
      particle interactions induce for the condensed gas a fundamental property
      characterizing "classical" superfluids. We present the structure of the vortex at
      ultralow temperatures and discuss the crucial effect of the thermal gas component
      to its energetic stability.

PMID- 11290020
TI  - Off-diagonal long-range order in Bose liquids: irrotational flow and quantization
      of circulation.
AB  - On the basis of gauge invariance, it is proven in an elementary and
      straightforward manner, but without invoking any ad hoc assumption, that the
      existence of off-diagonal long-range order in one-particle reduced density matrix
      in Bose liquids implies both the irrotational flow in a simply connected region
      and the quantization of circulation in a multiply connected region, the two
      fundamental properties of a Bose superfluid. The origin for both is the phase
      coherence of condensate wave functions. Some relevant issues are also addressed.

PMID- 11290021
TI  - Critical dimensions of the diffusion equation.
AB  - We study the evolution of a random initial field under pure diffusion in various
      space dimensions. From numerical calculations we find that the persistence
      properties of the system show sharp transitions at critical dimensions d(1)
      approximately 26 and d(2) approximately 46. We also give refined measurements of
      the persistence exponents for low dimensions.

PMID- 11290022
TI  - Hydrogen atom spectrum and the lamb shift in noncommutative QED.
AB  - We have calculated the energy levels of the hydrogen atom as well as the Lamb
      shift within the noncommutative quantum electrodynamics theory. The results show
      deviations from the usual QED both on the classical and the quantum levels. On
      both levels, the deviations depend on the parameter of space/space
      noncommutativity.

PMID- 11290023
TI  - Measuring the CP violating phase gamma using B+/- --> pi(+/-)pi(+)pi(-) and B+/- 
      -> K+/-pi(+)pi(-) decays.
AB  - A new and simple procedure to measure the angle gamma from B+/--->pi(+/-)pi(+)pi(
      ) and B+/--->K+/-pi(+)pi(-) decays using SU(3) symmetry is presented. It is based
      on a full Dalitz plot analysis of these decays. All diagrams, including strong
      and electroweak penguins, are considered in the procedure. The method is also
      free from final state interaction problems. The theoretical error in the
      extraction of gamma within the method should be of the order of 10(0) or even
      less. Taking into account the B-meson production in the first generation of B
      factories and recent measurements from CLEO, this method could bring the best
      measurement of gamma in the next years.

PMID- 11290024
TI  - QCD prediction for heavy boson transverse momentum distributions.
AB  - We investigate the predictive power of the Collins, Soper, and Sterman b-space
      QCD resummation formalism for transverse momentum ( Q(T)) distributions of heavy
      boson production in hadronic collisions. We show that the predictive power has a
      strong dependence on the collision energy sqrt[S] in addition to its well known
      Q2 dependence, and the sqrt[S] dependence improves the predictive power at
      collider energies. We demonstrate that, at the Fermilab Tevatron and the CERN LHC
      energies, the Q(T) distributions derived from b-space resummation are not
      sensitive to the nonperturbative input at large b, and give good descriptions of
      the Q(T) distributions of heavy boson production at all transverse momenta Q(T)<
      or =Q.

PMID- 11290025
TI  - Phenomenological consequences of right-handed down squark mixings.
AB  - The mixings of d(R) quarks, hidden from view in the standard model (SM), are
      naturally the largest if one has an Abelian flavor symmetry. With supersymmetry
      (SUSY) their effects can surface via d(R) squark loops. Squark and gluino masses
      are at TeV scale, but they can still induce effects comparable to SM in B(d) (or
      B(s)) mixings, while D0 mixing could be close to recent hints from data. In
      general, CP phases would be different from SM, as may be indicated by recent B
      factory data. Presence of nonstandard soft SUSY breakings with large tanbeta
      could enhance b-->dgamma (or sgamma) transitions.

PMID- 11290028
TI  - Measurements of F2 and xF(nu)(3) - xF(nu;)(3) from CCFR nu(mu)-Fe and nu;(mu)-Fe
      Data in a Physics Model-Independent Way.
AB  - We report on the extraction of the structure functions F2 and DeltaxF(3) =
      xF(nu)(3)-xF(nu;)(3) from CCFR nu(mu)-Fe and nu;(mu)-Fe differential cross
      sections. The extraction is performed in a physics model-independent (PMI) way.
      This first measurement of DeltaxF(3), which is useful in testing models of heavy
      charm production, is higher than current theoretical predictions. The ratio of
      the F2 (PMI) values measured in nu(mu) and mu scattering is in agreement (within
      5%) with the predictions of next-to-leading-order parton distribution functions
      using massive charm production schemes, thus resolving the long-standing
      discrepancy between the two sets of data.

PMID- 11290029
TI  - Linear polarization measurement of interband transitions in superdeformed 190hg:
      model-independent evidence for octupole vibrational structures.
AB  - The linear polarization of gamma rays between excited and yrast superdeformed
      (SD) states in 190Hg was measured using the four-element CLOVER detectors of the
      EUROBALL IV gamma-ray spectrometer. This measurement shows in a model-independent
      way that the interband transitions which compete with the highly collective in
      band quadrupole transitions are largely enhanced electric dipoles. Not only do
      these results represent the first measurement of the multipolarity of transitions
      between different SD states, but they also provide strong evidence for the
      interpretation of the structures in the SD minimum of the A approximately 190
      region in terms of octupole excitations.

PMID- 11290030
TI  - S17(0) determined from the Coulomb breakup of 83 MeV /nucleon 8B.
AB  - A kinematically complete measurement was made of the Coulomb dissociation of 8B
      nuclei on a Pb target at 83 MeV/nucleon. The cross section was measured at low
      relative energies in order to infer the astrophysical S factor for the
      7Be(p,gamma)8B reaction. A first-order perturbation theory analysis including E1,
      E2, and M1 transitions was employed to extract the E1 strength relevant to
      neutrino-producing reactions in the solar interior. By fitting the measured cross
      section from E(rel) = 130 to 400 keV, we find S17(0) = 17.8(+1.4)(-1.2) eV b.

PMID- 11290026
TI  - First observation of the decays B(0) --> D(*-)p_p pi+ and B(0) --> D(*-)p_n.
AB  - We report the first observation of exclusive decays of the type B-->D(*)N_NX,
      where N is a nucleon. Using a sample of 9.7x10(6)B_B pairs collected with the
      CLEO detector operating at the Cornell Electron Storage Ring, we measure the
      branching fractions B(B0-->D(*-)p_p pi(+)) = (6.5(+1.3)(-1.2)+/-1.0)x10(-4) and
      B(B0-->D(*-)p_n) = (14.5(+3.4)(-3.0)+/-2.7)x10(-4). Antineutrons are identified
      by their annihilation in the CsI electromagnetic calorimeter.

PMID- 11290031
TI  - In-plane elliptic flow of resonance particles in relativistic heavy-ion
      collisions.
AB  - We analyze the second Fourier coefficient v(2) of the pion azimuthal distribution
      in noncentral heavy-ion collisions in a relativistic hydrodynamic model. The
      exact treatment of the decay kinematics of resonances leads to almost vanishing
      azimuthal anisotropy of pions near the midrapidity, while the matter elliptic
      flow is in plane at freeze-out. In addition, we reproduce the rapidity dependence
      of v(2) for pions measured in noncentral Pb+Pb collisions at 158A GeV. This
      suggests that resonance particles as well as stable particles constitute the in
      plane flow and are important ingredients for the understanding of the observed
      pion flow.

PMID- 11290032
TI  - Observation of triplet doubly excited states in single photon excitation from
      ground state helium.
AB  - We have observed, for the first time, LS-forbidden triplet doubly excited states,
      in single photon excitation of ground state helium, below the second ionization
      threshold. These states are identified as (3)D(o) and (3)P(o) and their
      excitation is due to spin-orbit interaction that mixes them with the optically
      allowed (1)P(o) states. This observation is possible due to the very high
      efficiency in detecting metastable atoms created after the fluorescence decay of
      the doubly excited states, and the new capabilities of third generation
      synchrotron vacuum ultraviolet sources with high resolution beam lines.

PMID- 11290033
TI  - Electron energy spectra from intense laser double ionization of helium.
AB  - The double ionization of helium in the strong-field limit has been studied using
      an electron-ion coincidence technique. The observed double ionization electron
      energy spectra differ significantly from the single ionization distributions.
      This gives new support to the rescattering model of double ionization and
      explicitly reveals the role of backward electron emission following the e-2e
      ionizing collision.

PMID- 11290034
TI  - Atom symmetry break and metastable level coupling in rare gas atom-surface van
      der Waals interaction.
AB  - van der Waals interactions between an atom and a planar surface exhibit a
      quadrupolar component in D(2)(z)-D(2)/3 (D, atomic dipole; z, normal to surface).
      This coupling is responsible for an atom symmetry break, mixing levels of the
      same parity such as metastable 3P0, 3P2 levels of rare gas atoms. The strongly
      exoenergic 3P0-3P2 transition in Ar and Kr is observed by a time-of-flight
      technique, using as a surface the edge of a copper slit. The results confirm the
      predicted strong peaking of the angular distribution of inelastically scattered
      atoms and give a good estimate of the transition probability.

PMID- 11290027
TI  - Measurement of the relative branching fraction of upsilon(4S) to charged and
      neutral B-meson pairs.
AB  - We analyze 9.7x10(6) B_B pairs recorded with the CLEO detector to determine the
      production ratio of charged to neutral B-meson pairs produced at the Upsilon(4S)
      resonance. We measure the rates for B0-->J/psiK((*)0) and B+-->J/psiK((*)+)
      decays and use the world-average B-meson lifetime ratio to extract the relative
      widths f(+-) / f(00) = gamma(Upsilon(4S)-->B+B-) / gamma(Upsilon(4S)-->B0 B-0)) =
      1.04+/-0.07(stat)+/-0.04(syst). With the assumption that f(+-)+f(00) = 1, we
      obtain f(00) = 0.49+/-0.02(stat)+/-0.01(syst) and f(+-) = 0.51+/-0.02(stat)+/
      0.01(syst). This production ratio and its uncertainty apply to all exclusive B
      meson branching fractions measured at the Upsilon(4S) resonance.

PMID- 11290035
TI  - Entanglement, interference, and measurement in a degenerate parametric
      oscillator.
AB  - Quantum dynamical equations of motion for homodyne detection of the degenerate
      optical parametric oscillator are solved exactly. Nonclassical photon statistics
      are shown to be a consequence of interference of probability amplitudes,
      entanglement of photon pairs from such an oscillator, and the role of measurement
      in quantum evolution.

PMID- 11290036
TI  - Modification of self-induced transparency by a coherent control field.
AB  - We consider self-induced transparency (SIT) in a two-level atomic system in the
      presence of an additional control laser field. We find that the dynamics of the
      SIT process are profoundly modified by the control field, in a manner reminiscent
      of the modification of other nonlinear optical interactions through the process
      of electromagnetically induced transparency. The presence of the control field
      allows SIT to occur under a much broader range of conditions and leads to
      dramatically reduced values of the group velocity of the SIT soliton.

PMID- 11290037
TI  - Output functions and fractal dimensions in dynamical systems.
AB  - We present a novel method for the calculation of the fractal dimension of
      boundaries in dynamical systems, which is in many cases many orders of magnitude
      more efficient than the uncertainty method. We call it the output function
      evaluation (OFE) method. We show analytically that the OFE method is much more
      efficient than the uncertainty method for boundaries with D<0.5, where D is the
      dimension of the intersection of the boundary with a one-dimensional manifold. We
      apply the OFE method to a scattering system, and compare it to the uncertainty
      method. We use the OFE method to study the behavior of the fractal dimension as
      the system's dynamics undergoes a topological transition.

PMID- 11290038
TI  - Anticipation in the synchronization of chaotic semiconductor lasers with optical
      feedback.
AB  - The synchronization of chaotic semiconductor lasers with optical feedback is
      studied numerically in a one-way coupling configuration, in which a small amount
      of the intensity of one laser (master laser) is injected coherently into the
      other (slave laser). A regime of anticipated synchronization is found, in which
      the intensity of the slave laser is synchronized to the future chaotic intensity
      of the master laser. Anticipation is robust to small noise and parameter
      mismatches, but in this case the synchronization is not complete. It is also
      shown that anticipated synchronization occurs in coupled time-delay systems, when
      the coupling has a delay that is less than the delay of the systems.

PMID- 11290039
TI  - Photon statistics of a laser with slow inversion.
AB  - We have measured the photon number probability distribution of a laser in which
      the inversion is not slaved to the field. For the experiments, we have used a
      Nd(3+):YVO(4) laser which has a sufficiently slow inversion to allow measurement
      of the photon fluctuations at a time scale much shorter than that of the
      relaxation oscillations. The photon distribution function becomes highly
      nonstandard (i.e., non-Poissonian) in such a laser; this is consistent with
      available theoretical work. We point out the relevance of our results for the
      case of the semiconductor microlaser.

PMID- 11290040
TI  - Intermittent distribution of inertial particles in turbulent flows.
AB  - We consider inertial particles suspended in an incompressible turbulent flow.
      Because of particles' inertia their flow is compressible, which leads to
      fluctuations of concentration significant for heavy particles. We show that the
      statistics of these fluctuations is independent of details of the velocity
      statistics, which allows us to predict that the particles cluster on the viscous
      scale of turbulence and describe the probability distribution of concentration
      fluctuations. We discuss the possible role of the clustering in the physics of
      atmospheric aerosols, in particular, in cloud formation.

PMID- 11290041
TI  - Turbulent conductivity measurements in a spherical liquid sodium flow.
AB  - We report the first measurement of a reduction in the conductivity of liquid
      sodium due to turbulence in a spherical flow (the beta effect). The sodium is
      contained in a 0.15 m diameter sphere, typical flow speeds are about 1 m/s, and
      magnetic Reynold's numbers range from 1 to 8. We find a reduction from the
      molecular value of the conductivity of about 4%. Results are in rough agreement
      with simple predictions from mean-field electrodynamics.

PMID- 11290042
TI  - Simultaneous acceleration of multiply charged ions through a superconducting
      linac.
AB  - The possibility of simultaneously accelerating particles with a range of charge
      to-mass ratios ( approximately 20%) to the same energy is proposed and
      demonstrated for a superconducting linac. Uranium ions stripped in a foil with
      eight charge states have been accelerated through a portion of the ATLAS linac
      from 286 to 690 MeV, with 94% of the injected uranium in the accelerated beam.
      Emittance of the resultant beam has been measured and the energy spread was 1.3%
      compared to 0.4% for a single charge state. This development has immediate
      application to the high-intensity acceleration of heavy ions that are limited by
      ion-source intensities, such as the proposed Rare Isotope Accelerator Facility.

PMID- 11290043
TI  - Observation of the Askaryan effect: coherent microwave Cherenkov emission from
      charge asymmetry in high-energy particle cascades.
AB  - We present the first direct experimental evidence for the charge excess in high
      energy particle showers and corresponding radio emission predicted nearly 40
      years ago by Askaryan. We directed picosecond pulses of GeV bremsstrahlung
      photons at the SLAC Final Focus Test Beam into a 3.5 ton silica sand target,
      producing electromagnetic showers several meters long. A series of antennas
      spanning 0.3 to 6 GHz detected strong, subnanosecond radio-frequency pulses
      produced by the showers. Measurements of the polarization, coherence, timing,
      field strength vs shower depth, and field strength vs frequency are completely
      consistent with predictions. These measurements thus provide strong support for
      experiments designed to detect high-energy cosmic rays such as neutrinos via
      coherent radio emission from their cascades.

PMID- 11290044
TI  - Conversion of electrostatic to electromagnetic waves by superluminous ionization
      fronts.
AB  - The conversion of static electric fields to electromagnetic radiation by the
      incidence of a superluminous ionization front on plasma is investigated. For
      extremely superluminous fronts, the radiation is close to the plasma frequency
      and is converted with efficiency of order unity. A proof-of-principle experiment
      was conducted using semiconductor plasma containing an alternately charged
      capacitor array. The process has important implications in astrophysical plasmas,
      such as supernova emission, and to laboratory development of compact, coherent,
      tunable radiation sources in the THz range.

PMID- 11290045
TI  - Backscatter reduction using combined spatial, temporal, and polarization beam
      smoothing in a long-scale-length laser plasma.
AB  - Spatial, temporal, and polarization smoothing schemes are combined for the first
      time to reduce to a few percent the total stimulated backscatter of a NIF-like
      probe laser beam (2x10(15) W/cm (2), 351 nm, f/8) in a long-scale-length laser
      plasma. Combining temporal and polarization smoothing reduces simulated Brillouin
      scattering and simulated Raman scattering (SRS) up to an order of magnitude
      although neither smoothing scheme by itself is uniformly effective. The results
      agree with trends observed in simulations performed with the laser-plasma
      interaction code F3D simulations [R. L. Berger et al., Phys. Plasma 6, 1043
      (1999)].

PMID- 11290046
TI  - Sandpile model with tokamaklike enhanced confinement phenomenology.
AB  - Confinement phenomenology characteristic of magnetically confined plasmas emerges
      naturally from a simple sandpile algorithm when the parameter controlling
      redistribution scale length is varied. Close analogs are found for enhanced
      confinement, edge pedestals, and edge localized modes (ELMs), and for the
      qualitative correlations between them. These results suggest that tokamak
      observations of avalanching transport are deeply linked to the existence of
      enhanced confinement and ELMs.

PMID- 11290047
TI  - Structure determination of the Si3N4/Si(111)- (8 x 8) surface: a combined study
      of Kikuchi electron holography, scanning tunneling microscopy, and ab initio
      calculations.
AB  - A comprehensive atomic model for the reconstructed surface of Si3N4 thin layer
      grown on Si(111) is presented. Kikuchi electron holography images clearly show
      the existence of adatoms on the Si3N4(0001)/Si(111)-(8x8) surface. Compared with
      the ab initio calculations, more than 30 symmetry-inequivalent atomic pairs in
      the outmost layers are successfully identified. Scanning tunneling microscopy
      (STM) images show diamond-shaped unit cells and nine adatoms in each cell. High
      resolution STM images reveal extra features and are in good agreement with the
      partial charge density distribution obtained from total-energy calculations.

PMID- 11290048
TI  - Freedericksz transition in confined liquid crystals: concentration and
      microgeometry effects.
AB  - The Freedericksz transition in dispersions of liquid-crystal droplets is studied
      analytically by balancing the electrostatic energy of the droplets with a strong
      anchoring elastic energy. Explicit dependence of the transition threshold field
      on the liquid-crystal volume fraction and the spatial arrangement of the droplets
      is obtained for the first time. As a result of the confined geometry, this
      threshold field does not depend on the thickness of the sample and splitting of
      the transition occurs in some situations.

PMID- 11290049
TI  - Amorphous structures in the immiscible Ag-Ni system.
AB  - Vapor quenching in the phase-separating Ag-Ni system creates alloys that appear
      homogeneously amorphous under conventional probes. However, an atomic-level
      structural analysis based on extended x-ray absorption fine structures in
      combination with reverse Monte Carlo and molecular dynamics simulations
      demonstrates that these new phases are characterized by nonuniform, spinodal-like
      structures on an extremely fine scale. This heterogeneous nature of the structure
      is directly responsible for the unexpectedly low heat (and temperature) of
      crystallization observed in calorimetric measurements.

PMID- 11290050
TI  - On the constitution of sodium at higher densities.
AB  - Using density functional theory the atomic and electronic structures of sodium
      are predicted to depart substantially from those expected of simple metals for
      r(s)<2.48 ( p>130 GPa). Newly predicted phases include those with low structural
      symmetry and semimetallic electronic properties (including zero-gap
      semiconducting limiting behavior), and even those that raise the possibility of
      superconductivity, all at currently achievable pressures. Important differences
      emerge between sodium and lithium at high densities, and these are attributable
      to corresponding differences in their respective cores.

PMID- 11290051
TI  - Hole trapping at Al impurities in silica: a challenge for density functional
      theories.
AB  - The atomic geometry and electronic structure around a neutral substitutional Al
      impurity in silica is investigated using either the unrestricted Hartree-Fock
      (UHF) approximation, or Beckes three-parameter hybrid functional (B3LYP). It is
      found that the B3LYP functional fails to describe the structural distortions
      around the Al impurity, while the UHF results are consistent with experimental
      information. We argue that the failure of the B3LYP functional is caused by the
      incomplete self-interaction cancellation usually present in density functional
      theories.

PMID- 11290052
TI  - Evidence for a quasi-two-dimensional proton glass state in Cs5H3(SO4)(4); xH(2)O
      Crystals.
AB  - We describe damping of hypersonic and ultrasonic longitudinal acoustic (LA)
      phonons in crystals of Cs 5H (3)(SO (4))(4);xH 2O (PCHS) between 100 and 360 K.
      The damping of LA phonons exhibits strong dispersion caused by relaxation
      processes in the region of transformation into the glasslike phase (T(g)
      approximately 260 K). Near T(g) the damping of ultrasonic phonons propagating in
      the basal plane reflects the cooperative freezing of acid protons. The damping of
      LA phonons propagating perpendicular to the basal plane can be fit by the Debye
      model and is due to the interaction between protons and LA phonons. This suggests
      that the proton glass state that is realized at T<T(g) has a quasi-two
      dimensional nature.

PMID- 11290053
TI  - Atomic wire oxidation of H-terminated Si(100)-( 2x1): domino reaction via
      oxidation and H migration.
AB  - We studied oxidation at a dangling bond (DB) on the H-terminated Si(100) surface
      by the first-principles calculations. We found that oxidation easily occurs at
      the exposed DB on the H-terminated Si(100) surface. The dissociated O atoms are
      chemisorbed at a dimer bond and a back bond, resulting in adjacent H atom
      migration onto the DB. As a consequence of the alternate oxidation and subsequent
      H atom migration processes, the atomic wire oxidation is actually found to occur
      on the H-terminated Si(100) surface at low temperatures without desorbing H
      atoms, as observed in our scanning tunneling microscopy experiment.

PMID- 11290054
TI  - Electronic band structure of Gd: a consistent description.
AB  - The dispersion of the Gd (5d6s)-valence bands has been investigated by means of
      spin- and angle-resolved photoemission. The spin analysis of various spectral
      features shows that their weak dispersion and unusual broadening is due to the
      photoelectron lifetime rather than to correlation induced band narrowing as
      previously proposed. These results resolve a long-standing discrepancy between
      theoretical and experimental descriptions of the rare earth band structure.

PMID- 11290055
TI  - Resonant tunneling mediated by resonant emission of intersubband plasmons.
AB  - We study tunneling through resonant tunneling diodes (RTD) with very long emitter
      drift regions (up to 2 microm). In such diodes, charge accumulation occurs near
      the double barrier on the emitter side, in a self-induced potential pocket. This
      leads to a substantial enhancement of the wave function overlap between states of
      the pocket and the RTD, and, consequently, to increased off-resonant current
      mediated by various scattering processes. For RTD with the longest drift region
      (2 microm), an additional strong current peak is observed between the first and
      the second resonant peaks. We attribute this pronounced feature to the
      intersubband transitions mediated by resonant emission of intersubband plasmons.

PMID- 11290056
TI  - Detecting the Kondo screening cloud around a quantum dot.
AB  - A fundamental prediction of scaling theories of the Kondo effect is the screening
      of an impurity spin by a cloud of electrons spread out over a mesoscopic
      distance. This cloud has never been observed experimentally. Recently, aspects of
      the Kondo effect have been observed in experiments on quantum dots embedded in
      quantum wires. Since the length of the wire may be of order the size of the
      screening cloud, such systems provide an ideal opportunity to observe it. We
      point out that persistent current measurements in a closed ring provide a
      conceptually simple way of detecting this fundamental length scale.

PMID- 11290057
TI  - In-plane magnetic field-induced spin polarization and transition to insulating
      behavior in two-dimensional hole systems.
AB  - Using a novel technique, we make quantitative measurements of the spin
      polarization of dilute [ (3.4-6.8)x10(10) cm(-2)] GaAs (311)A two-dimensional
      holes as a function of an in-plane magnetic field. As the field is increased the
      system gradually becomes spin polarized, with the degree of spin polarization
      depending on the orientation of the field relative to the crystal axes. Moreover,
      the behavior of the system turns from metallic to insulating before it is fully
      spin polarized. The minority-spin population at the transition is approximately
      8x10(9) cm(-2), close to the density below which the system makes a transition to
      an insulating state in the absence of a magnetic field.

PMID- 11290058
TI  - Nonlinear electron current through a short molecular wire.
AB  - The voltage and the temperature behavior of inelastic interelectrode current
      mediated by a short molecular wire is analyzed within a nonlinear kinetic
      approach that accounts for strong Coulomb repulsion between transferring
      electrons. When the coupling to the heat bath occurs via high-frequency vibration
      modes we predict a generally nonlinear current-voltage characteristics (an Ohmic
      behavior at small voltage, rising towards saturation and being followed by an
      abrupt decrease at large voltage) and a bell-shaped current response vs
      temperature at not too large temperatures.

PMID- 11290059
TI  - Nesting induced precursor effects: a renormalization group approach.
AB  - We develop a controlled weak coupling renormalization group (RG) approach to
      itinerant electrons. Within this formalism we rederive the phase diagram for two
      dimensional non-nested systems. We then study how nesting modifies this phase
      diagram. We show that competition between particle-particle and particle-hole
      channels leads to the manifestation of an unstable precursor fixed point in the
      RG flow. This effect should be experimentally measurable, and may be relevant for
      an explanation of pseudogaps in the high temperature superconductors, as a
      crossover phenomenon.

PMID- 11290060
TI  - Magnetic-flux penetration and critical currents in superconducting strips with
      slits.
AB  - We theoretically investigate transport-current-induced magnetic-flux penetration
      into superconducting strip lines with slits. Even when the individual strips have
      no bulk pinning, geometrical barriers prevent penetration of magnetic flux into
      the innermost strips while flux quasistatically penetrates into the outermost
      slits. The critical current of strip lines with 2N slits at zero applied magnetic
      field is found to be enhanced by a factor of (N+1)(1/2) above that of a single
      strip line without slits. Under suitable conditions, a domelike flux distribution
      due to the geometrical barrier can appear in the individual strips even in the
      absence of an applied magnetic field.

PMID- 11290061
TI  - Magnetic dissipation and fluctuations in individual nanomagnets measured by
      ultrasensitive cantilever magnetometry.
AB  - Cantilever magnetometry with moment resolution better than 10(4)micro(B) was used
      to study individual nanomagnets. By using the fluctuation-dissipation theorem to
      interpret measurements of field-induced cantilever damping, the low frequency
      spectral density of magnetic fluctuations could be determined with resolution
      better than 1micro(B) Hz-1/2. Cobalt nanowires exhibited significant magnetic
      dissipation and the associated magnetic fluctuations were found to have 1/f
      frequency dependence. In individual submicron rare-earth alloy magnets, the
      dissipation/fluctuation was very small and not distinguishable from that of a
      bare silicon cantilever.

PMID- 11290062
TI  - Spin reorientation at the antiferromagnetic NiO(001) surface in response to an
      adjacent ferromagnet.
AB  - Polarization dependent x-ray photoemission electron microscopy was used to
      investigate the spin structure near the surface of an antiferromagnetic NiO(001)
      single crystal in response to the deposition of a thin ferromagnetic Co film. For
      the cleaved NiO surface we observe only a subset of bulklike antiferromagnetic
      domains which is attributed to minimization of dipolar energies. Upon Co
      deposition a spin reorientation near the NiO interface occurs, with the
      antiferromagnetic spins rotating in plane, parallel to the spins of the Co layer.
      Our results demonstrate that the spin configuration in an antiferromagnet near
      its interface with a ferromagnet may significantly deviate from that in the bulk
      antiferromagnet.

PMID- 11290063
TI  - Strong anisotropy of superexchange in the copper-oxygen chains of La(14)
      xCaxCu24O41.
AB  - Electron spin resonance data of Cu2+ ions in La(14)-xCaxCu24O41 single crystals
      (x = 9,11,12) reveal a very large width of the resonance line in the paramagnetic
      state. This signals an unusually strong anisotropy of approximately 10% of the
      isotropic Heisenberg superexchange in the Cu-O chains of this compound. The
      strong anisotropy can be explained by the specific geometry of two symmetrical 90
      degrees Cu-O-Cu bonds, which boosts the importance of orbital degrees of freedom.
      Our data show the apparent limitations of the applicability of an isotropic
      Heisenberg model to the low-dimensional cuprates.

PMID- 11290064
TI  - Photoinduced phase transition to a new macroscopic spin-crossover-complex phase.
AB  - We clarified for the first time that the photoinduced phase is quite different in
      structure from the thermally induced phase by the resonant Raman spectroscopy in
      the spin-crossover complex, [Fe(2-pic)(3)]-Cl2EtOH. In the photoinduced phase we
      observed a number of additional lines assigned to infra-active vibrational modes
      which are strongly prohibited by selection rules in the thermally induced phase.
      These results indicate that a dramatic symmetry lowering should take place in the
      photoinduced phase. The cooperative Jahn-Teller transformation is a plausible
      candidate for the symmetry lowering in the photoinduced phase.

PMID- 11290065
TI  - Exponential gain in quantum computing of quantum chaos and localization.
AB  - We present a quantum algorithm which simulates the quantum kicked rotator model
      exponentially faster than classical algorithms. This shows that important
      physical problems of quantum chaos, localization, and Anderson transition can be
      modeled efficiently on a quantum computer. We also show that a similar algorithm
      simulates efficiently classical chaos in certain area-preserving maps.

PMID- 11290066
TI  - Magnetic resonance force microscopy quantum computer with tellurium donors in
      silicon.
AB  - We propose a magnetic resonance force microscopy (MRFM)-based nuclear spin
      quantum computer using tellurium impurities in silicon. This approach to quantum
      computing combines well-developed silicon technology and expected advances in
      MRFM. Our proposal does not use electrostatic gates to realize quantum logic
      operations.

PMID- 11290067
TI  - Extreme damping in composite materials with a negative stiffness phase.
AB  - Composites with negative stiffness inclusions in a viscoelastic matrix are shown
      to have higher stiffness and mechanical damping tandelta than that of either
      constituent and exceeding conventional bounds. The causal mechanism is a greater
      deformation in and near the inclusions than the composite as a whole. Though a
      block of negative stiffness is unstable, negative stiffness inclusions in a
      composite can be stabilized by the surrounding matrix. Such inclusions may be
      made from single domains of ferroelastic material below its phase transition
      temperature or from prebuckled lumped elements.

PMID- 11290068
TI  - Sensory coding and the second spectra of natural signals.
AB  - Natural auditory and visual stimuli are shown to demonstrate consistent non
      Gaussian signatures: their phase-only second spectra behave approximately as the
      inverse square root of frequency, a property which is due to a predominance of
      difference beats between Fourier components at slightly offset frequencies. These
      second spectra also demonstrate statistical scale invariance, a hypothesis which
      is tested explicitly by computing phase-only second spectra from bandpass
      filtered data. The bandpass frequency selectivity observed experimentally in
      sensory cells is shown to be qualitatively consistent with a strategy of
      exploiting the non-Gaussian structure of natural signals.

PMID- 11290069
TI  - Fast voltage transients in capacitive silicon-to-cell stimulation detected with a
      luminescent molecular electronic probe.
AB  - The capacitive stimulation of nerve cells from semiconductor chips is a
      prerequisite for the development of neuroelectronic devices. We report on the
      primary response of a cell membrane to a voltage step applied to oxidized
      silicon. It is observed with a luminescent voltage-sensitive dye. We find
      exponential voltage transients with a time constant of 1-5 micros. We assign the
      short response to an electrical decoupling by a thin film of electrolyte between
      oxide and membrane. The high-pass filtering of stimulation is a crucial
      constraint for the development of silicon-to-neuron interfaces.

PMID- 11290070
TI  - Small world effect in an epidemiological model.
AB  - A model for the spread of an infection is analyzed for different population
      structures. The interactions within the population are described by small world
      networks, ranging from ordered lattices to random graphs. For the more ordered
      systems, there is a fluctuating endemic state of low infection. At a finite value
      of the disorder of the network, we find a transition to self-sustained
      oscillations in the size of the infected subpopulation.

PMID- 11290071
TI  - Universality of decoherence.
AB  - We consider environment induced decoherence of quantum superpositions to mixtures
      in the limit in which that process is much faster than any competing one
      generated by the Hamiltonian H(sys) of the isolated system. While the golden rule
      then does not apply we can discard H(sys). By allowing for couplings to different
      reservoirs, we reveal decoherence as a universal short-time phenomenon
      independent of the character of the system as well as the bath and of the basis
      the superimposed states are taken from. We discuss consequences for the classical
      behavior of the macroworld and quantum measurement: For decoherence of
      superpositions of macroscopically distinct states H(sys) is always negligible.

PMID- 11290072
TI  - Dark solitons in a two-component Bose-Einstein condensate.
AB  - The creation and interaction of dark solitons in a two-component Bose-Einstein
      condensate is investigated. For a miscible case, the interaction of dark solitons
      in different components is studied. Various possible scenarios are presented,
      including the formation of a soliton-soliton bound pair. We also analyze the
      soliton propagation in the presence of domains, and show that a dark soliton can
      be transferred from one component to the other at the domain wall when it exceeds
      a critical velocity. For lower velocities multiple reflections within the domain
      are observed, where the soliton is evaporated and accelerated after each
      reflection until it finally escapes from the domain.

PMID- 11290073
TI  - Use of surface-wave spectroscopy to characterize tilt modes of a vortex in a Bose
      Einstein condensate.
AB  - A vortex in a condensate in a nonspherical trapping potential will in general
      experience a torque. The torque will induce tilting of the direction of the
      vortex axis. We observe this behavior experimentally and show that by applying
      small distortions to the trapping potential, we can control the tilting behavior.
      By suppressing vortex tilt, we have been able to hold the vortex axis along the
      line of sight for up to 15 sec. Alternatively, we can induce a 180 degrees tilt,
      effectively reversing the charge on the vortex as observed in the lab frame. We
      characterize the vortex nondestructively with a surface-wave spectroscopic
      technique.

PMID- 11290074
TI  - Watching dark solitons decay into vortex rings in a Bose-Einstein condensate.
AB  - We have created spatial dark solitons in two-component Bose-Einstein condensates
      in which the soliton exists in one of the condensate components and the soliton
      nodal plane is filled with the second component. The filled solitons are stable
      for hundreds of milliseconds. The filling can be selectively removed, making the
      soliton more susceptible to dynamical instabilities. For a condensate in a
      spherically symmetric potential, these instabilities cause the dark soliton to
      decay into stable vortex rings. We have imaged the resulting vortex rings.

PMID- 11290075
TI  - Exclusion statistics in a trapped two-dimensional Bose gas.
AB  - We study the statistical mechanics of a two-dimensional Bose gas with a repulsive
      delta-function interaction, using a mean-field approximation. By a direct
      counting of states we establish that this model obeys exclusion statistics and is
      equivalent to an ideal exclusion-statistics gas. We also show that this result is
      consistent with a full quantum-mechanical treatment of a quasi-two-dimensional
      system.

PMID- 11290076
TI  - Transmission of noise coded versus additive signals through a neuronal ensemble.
AB  - Neuronal populations receive signals through temporally inhomogeneous spike
      trains which can be approximated by an input consisting of a time dependent mean
      value (additive signal) and noise with a time dependent intensity (noise coded
      signal). We compare the linear response of an ensemble of model neurons to these
      signals. Our analytical solution for the mean activity demonstrates the high
      efficiency of the transmission of a noise coded signal in a broad frequency band.
      For both kinds of signal we show that the transmission by the ensemble reveals
      stochastic resonance as well as a nonmonotonous dependence on the driving
      frequency.

PMID- 11290077
TI  - Nonextensive thermostatistics and the H theorem.
AB  - The kinetic foundations of Tsallis' nonextensive thermostatistics are
      investigated through Boltzmann's transport equation approach. Our analysis
      follows from a nonextensive generalization of the "molecular chaos hypothesis."
      For q>0, the q-transport equation satisfies an H theorem based on Tsallis
      entropy. It is also proved that the collisional equilibrium is given by Tsallis'
      q-nonextensive velocity distribution.

PMID- 11290078
TI  - Deflection of spacecraft trajectories as a new test of general relativity.
AB  - We derive a simple formula which gives the general relativistic deflection of a
      spacecraft, idealized as a point mass, for all values of the asymptotic speed
      V(infinity) (0< or =V(infinity)< or =1). Using this formula we suggest a new test
      of general relativity (GR) which can be carried out during a proposed
      interstellar mission that involves a close pass of the Sun. We show that, with
      foreseeable improvements in spacecraft tracking sensitivity, the deflection of a
      spacecraft's trajectory in the gravitational field of the Sun could provide a new
      test of GR.

PMID- 11290079
TI  - From computation to black holes and space-time foam.
AB  - We show that quantum mechanics and general relativity limit the speed nu of a
      simple computer (such as a black hole) and its memory space I to I(nu2) less,
      similar(t(-2))P, where t(P) is the Planck time. We also show that the lifetime of
      a simple clock and its precision are similarly limited. These bounds and the
      holographic bound originate from the same physics that governs the quantum
      fluctuations of space-time. We further show that these physical bounds are
      realized for black holes, yielding the correct Hawking black hole lifetime, and
      that space-time undergoes much larger quantum fluctuations than conventional
      wisdom claims-almost within range of detection with modern gravitational-wave
      interferometers.

PMID- 11290081
TI  - Study of the decay D0 --> K+pi-.
AB  - Using a large sample of photoproduced charm mesons from the FOCUS experiment at
      Fermilab (FNAL-E831), we observe the decay D0-->K+pi- with a signal yield of
      149+/-31 events compared to a similarly cut sample consisting of 36 760+/-195 D0-
      >K-pi+ events. We use the observed ratio of D0-->K+pi- to D0-->K-pi+ (0.404+/
      0.085+/-0.025)% to obtain a relationship between the D0 mixing and doubly Cabibbo
      suppressed decay parameters.

PMID- 11290080
TI  - Search for B --> tau(nu) and B --> K(nu)nu.
AB  - We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged
      B meson decays. We exclusively reconstruct the companion B decay to suppress
      background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x
      10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(
      4) at 90% confidence level.

PMID- 11290082
TI  - Measurement of the recoil polarization in the p(e-->, e'p-->)pi(0) reaction at
      the Delta(1232) resonance.
AB  - The recoil proton polarization has been measured in the p(e-->,e'p-->)pi(0)
      reaction in parallel kinematics around W = 1232 MeV, Q2 = 0.121 (GeV/c)2, and
      epsilon = 0.718 using the polarized cw electron beam of the Mainz Microtron. All
      three proton polarization components, Px/P(e) = (-11.4+/-1.3+/-1.4)%, P(y) = (
      43.1+/-1.3+/-2.2)%, and P(z)/P(e) = (56.2+/-1.5+/-2.6)%, could be measured
      simultaneously. The Coulomb quadrupole to magnetic dipole ratio, CMR = (-6.4+/
      0.7(stat)+/-0.8(syst))%, was determined from Px in the framework of the Mainz
      Unitary Isobar Model. The consistency among the reduced polarizations and the
      extraction of the ratio of longitudinal-to-transverse response is discussed.

PMID- 11290083
TI  - Search for quadrupole strength in the electroexcitation of the delta+(1232).
AB  - High-precision 1H(e,e'p)pi(0) measurements at Q2 = 0.126 (GeV/c)2 are reported,
      which allow the determination of quadrupole amplitudes in the gamma*N-->Delta
      transition; they simultaneously test the reliability of electroproduction models.
      The derived quadrupole-to-dipole ( I = 3/2) amplitude ratios, R(SM) = (-6.5+/
      0.2(stat+sys)+/-2.5(mod))% and R(EM) = (-2.1+/-0.2(stat+sys)+/-2.0(mod))%, are
      dominated by model error. Previous R(SM) and R(EM) results should be reconsidered
      after the model uncertainties associated with the method of their extraction are
      taken into account.

PMID- 11290084
TI  - Parity violation observed in the beta decay of magnetically trapped 82Rb atoms.
AB  - Laser cooling and atomic trapping techniques have been employed to confine
      polarized 82Rb atoms ( T1/2 = 75 s) in a magnetic time-orbiting-potential (TOP)
      trap. We have observed the parity-violating correlation between the emitted
      positron momentum and the parent nuclear spin as a continuous function of angle
      and positron energy for this pure Gamow-Teller (GT) transition. These proof-of
      principle measurements demonstrate the utility of exploring fundamental
      symmetries in a TOP trap and the steps required to improve sensitivity in the
      search for physics beyond the standard model.

PMID- 11290085
TI  - Quantum calculation of the dipole excitation in fusion reactions.
AB  - The excitation of the giant dipole resonance induced by fusion reaction is
      studied with N/Z asymmetry in the entrance channel. The time dependent Hartree
      Fock solution exhibits a strong dipole vibration which can be associated with a
      giant vibration along the main axis of the deformed compound nucleus. This dipole
      motion appears to be nonlinearly coupled to the shape oscillation, leading to a
      strong modulation of its frequency. These phenomena can be detected in the gamma
      ray emission from hot compound nuclei.

PMID- 11290087
TI  - Resolving the antibaryon-production puzzle in high-energy heavy-ion collisions.
AB  - We argue that the observed antiproton production in heavy-ion collisions at CERN
      SPS energies can be understood if (contrary to most sequential scattering
      approaches) the backward direction in the process pP<-->n(pi) (with n = 5-6) is
      consistently accounted for within a thermal framework. Employing the standard
      picture of subsequent chemical and thermal freezeout, which induces an
      oversaturation of pion number with associated chemical potentials of mu(pi)
      approximately 60-80 MeV, enhances the backward reaction substantially. The
      resulting rates turn out to be large enough to maintain an antiproton abundance
      at thermal freezeout in accordance with the measured p/p ratio in Pb(158A GeV)+Pb
      collisions.

PMID- 11290086
TI  - Polarization measurements in high-energy deuteron photodisintegration.
AB  - We present measurements of the recoil proton polarization for the d(gamma-->,p-
      >)n reaction at straight theta(c.m.) = 90 degrees for photon energies up to 2.4
      GeV. These are the first data in this reaction for polarization transfer with
      circularly polarized photons. The induced polarization p(y) vanishes above 1 GeV,
      contrary to meson-baryon model expectations, in which resonances lead to large
      polarizations. However, the polarization transfer Cx does not vanish above 1 GeV,
      inconsistent with hadron helicity conservation. Thus, we show that the scaling
      behavior observed in the d(gamma,p)n cross sections is not a result of
      perturbative QCD. These data should provide important tests of new
      nonperturbative calculations in the intermediate energy regime.

PMID- 11290088
TI  - Multicomponent density-functional theory for electrons and nuclei.
AB  - A multicomponent density-functional theory is developed for the combined system
      of electrons and nuclei. We construct approximate functionals for the electron
      nuclear correlation energy and illustrate the theory by explicit calculations for
      the H+2 molecular ion.

PMID- 11290089
TI  - Double-well states of ungerade symmetry in H2: first observation and comparison
      with Ab initio calculations.
AB  - The observation of a new class of long-lived outer well states of ungerade
      symmetry (B"B1Sigma+u) in molecular hydrogen, lying above the ionization
      threshold, is reported. Rovibrational levels within a potential extended over
      internuclear separations of R = 7-25 a.u. are experimentally investigated in a
      triple resonance scheme. Good agreement ( <0.5 cm(-1)) with updated ab initio
      calculations is found for vibrational levels up to v = 26, demonstrating that
      such calculations can now be extended to this energetic range above ionization,
      as long as interaction with the Rydberg manifolds is shielded by a barrier. The
      dynamical behavior (predissociation and autoionization) of this class of " u"
      symmetry states is remarkably different from similar outer well states of " g"
      symmetry; this phenomenon can be understood from the structure of doubly excited
      electronic states.

PMID- 11290090
TI  - Ag8 fluorescence in argon.
AB  - The fluorescence of Ag8 in an argon matrix and in argon droplets is reported.
      This is the first unambiguous assignment of the fluorescence of a metal cluster
      larger than the tetramer, indicating that the excited state lifetime is longer
      than previously thought. It is discussed as a possible result of a matrix cage
      effect. The excitation spectrum is compared with two-photon-ionization
      measurements of Ag8 in helium droplets and to known absorption data. The
      agreement is excellent. We propose that the excited states relax rapidly through
      vibrational coupling to a long-lived state, from which the fluorescence occurs.

PMID- 11290091
TI  - Multiply charged metal cluster anions.
AB  - Formation and stability patterns of silver dianionic and gold trianionic clusters
      are investigated with Penning-trap experiments and a shell-correction method
      including shape deformations. The theoretical predictions pertaining to the
      appearance sizes and electronic shell effects are in remarkable agreement with
      the experiments. Decay of the multiply anionic clusters occurs predominantly by
      electron tunneling through a Coulomb barrier rather than via fission, leading to
      appearance sizes unrelated to those of multiply cationic clusters.

PMID- 11290092
TI  - Spherical growth and surface-quasifree vibrations of Si nanocrystallites in Er
      doped Si nanostructures.
AB  - Si-based Er-doped Si nanostructures were fabricated for exploring efficient light
      emission from Er ions and Si nanocrystallites. High-resolution transmission
      electron microscopy observations reveal that Si nanocrystallites are spherically
      embedded in the SiO2 matrix. Energy-dispersive x-ray analysis indicates that the
      Er centers are distributed at the surfaces of nanocrystallites surrounded by the
      SiO2 matrix. Low-frequency Raman scattering investigation shows that Lamb's
      theory can be adopted to exactly calculate the surface vibration frequencies from
      acoustic phonons confined in spherical Si nanocrystallites and the matrix effects
      are negligible.

PMID- 11290093
TI  - Saturated amplification of a collisionally pumped optical-field-ionization soft X
      ray laser at 41.8 nm.
AB  - We report the first saturated amplification of an optical-field-ionization soft x
      ray laser. The amplifying medium is generated by focusing a circularly polarized
      330-mJ, 35-fs, 10-Hz Ti:sapphire laser system in a few-mm cell filled with xenon.
      A gain of 67 cm(-1) on the 4d(9)5p-4d(9)5d transition at 41.8 nm in Pd-like xenon
      and a gain-length product of 15 have been inferred at saturation. This source
      delivers about 5 x 10(9) photons per pulse. The influence of the pumping energy
      and the laser polarization on the lasing output are also presented.

PMID- 11290094
TI  - Waveguiding in surface plasmon polariton band gap structures.
AB  - Using near-field optical microscopy, we investigate propagation and scattering of
      surface plasmon polaritons (SPP's) excited in the wavelength range of 780-820 nm
      at nanostructured gold-film surfaces with areas of 200-nm-wide scatterers
      arranged in a 400-nm-period triangular lattice containing line defects. We
      observe the SPP reflection by such an area and SPP guiding along line defects at
      782 nm, as well as significant deterioration of these effects is 815 nm, thereby
      directly demonstrating the SPP band gap effect and showing first examples of SPP
      channel waveguides in surface band gap structures.

PMID- 11290095
TI  - Experimental and theoretical evidence for the existence of absolute acoustic band
      gaps in two-dimensional solid phononic crystals.
AB  - Experimental measurements of acoustic transmission through a solid-solid two
      dimensional binary-composite medium constituted of a triangular array of parallel
      circular steel cylinders in an epoxy matrix are reported. Attention is restricted
      to propagation of elastic waves perpendicular to the cylinders. Measured
      transmitted spectra demonstrate the existence of absolute stop bands, i.e., band
      gaps independent of the direction of propagation in the plane perpendicular to
      the cylinders. Theoretical calculations of the band structure and transmission
      spectra using the plane wave expansion and the finite difference time domain
      methods support unambiguously the absolute nature of the observed band gaps.

PMID- 11290096
TI  - Convection, heaping, and cracking in vertically vibrated granular slurries.
AB  - We address the situation in which vibration is applied to thin layers of granular
      material with water filling the pore space, but with air above. Beyond a critical
      drive parameter we observe heap-shaped convecting domains of nontrivial topology,
      which exhibit cracks as the forcing amplitude is further increased. We summarize
      these results in a phase diagram, understand the onset of the convecting heaps as
      a manifestation of the Rayleigh-Taylor instability for fluids, and measure the
      response of isolated convecting structures.

PMID- 11290097
TI  - Self-diffusion in a gas-fluidized bed of fine powder.
AB  - We have investigated the self-diffusion in a stable gas-fluidized bed of fine
      powder. Two regimes have been observed: for gas velocities v(g) above the minimum
      fluidization velocity v(m) and below a critical gas velocity v(c) smaller than
      the minimum bubbling velocity v(b) the powder does not mix. Experimental
      measurements show the existence of yield stresses in this regime which are
      responsible for the static behavior of the bed. For v(g)>v(c) the yield stress
      vanishes; the bed behaves like a fluid and displays a diffusive dynamics. In this
      region we have found that the diffusion coefficient D increases with gas velocity
      until the bed expansion approaches its maximum value.

PMID- 11290098
TI  - Magnetic field saturation in the Riga dynamo experiment.
AB  - After the dynamo experiment in November 1999 [A. Gailitis et al., Phys. Rev.
      Lett. 84, 4365 (2000)] had shown magnetic field self-excitation in a spiraling
      liquid metal flow, in a second series of experiments emphasis was placed on the
      magnetic field saturation regime as the next principal step in the dynamo
      process. The dependence of the strength of the magnetic field on the rotation
      rate is studied. Various features of the saturated magnetic field are outlined
      and possible saturation mechanisms are discussed.

PMID- 11290099
TI  - Multiple Coulomb ordered strings of ions in a storage ring.
AB  - We explain that the anomalous frequency shifts of very close masses obtained in
      the high precision mass measurement experiments in the ESR storage ring result
      from the locking of Coulomb interacting strings of ions. Here two concentric
      strings which run horizontally close to each other are captured into a single
      string if their thermal clouds overlap and give up their identity.

PMID- 11290100
TI  - Search of self-organized criticality processes in magnetically confined plasmas:
      hints from the reversed field pinch configuration.
AB  - In order to test the self-organized criticality (SOC) paradigm in transport
      processes, a novel technique has been applied for the first time to plasmas
      confined in reversed field pinch configuration. This technique consists of an
      analysis of the probability distribution function of the times between bursts in
      density fluctuations measured by microwave reflectometry and electrostatic
      probes. The same analysis has also been applied to intermittent events sorted out
      from the Gaussian background. In both cases, the experimental results disagree
      with the predictions for a SOC system.

PMID- 11290101
TI  - Generation of suprathermal electrons during magnetic reconnection at the sawtooth
      crash and disruption instability in the T-10 tokamak.
AB  - Evidence for excitation of suprathermal electrons ( E(gamma) approximately 20-100
      keV) during magnetic reconnection in the T-10 tokamak is presented through
      analysis of the x-ray measurements with enhanced spatial and time resolution. A
      toroidally viewing x-ray imaging system and a fast hard x-ray detector placed
      inside the tokamak vessel allow identification of bursts of the nonthermal x-ray
      radiation around X points of the m = 1 and m = 2 magnetic islands during the
      sawtooth crash and prior to the energy quench at the density limit disruption.

PMID- 11290102
TI  - Observation of toroidal flow antiparallel to the <E(r) x B(straight theta)> drift
      direction in the hot electron mode plasmas in the compact helical system.
AB  - A toroidal flow antiparallel to the <E(r) x B(straight theta)> drift direction is
      observed in the hot electron mode plasmas when a large positive electric field
      and a sharp electron temperature gradient are sustained inside the internal
      transport barrier in the Compact Helical System. This toroidal flow reaches up to
      5x10(4) m/s at the plasma center, and it is large enough to reverse the toroidal
      flow driven by a tangentially injected neutral beam. These observations clearly
      show the plasma favors flow in the minimum nablaB direction at the transport
      barrier.

PMID- 11290104
TI  - Reentrant ferroelectricity in liquid crystals.
AB  - The ferroelectric (Sm C*)-antiferroelectric (Sm C*A)-reentrant ferroelectric (re
      Sm C*) phase temperature sequence was observed for systems with competing
      synclinic-anticlinic interactions. The basic properties of this system are as
      follows: (i) the Sm C* phase is metastable in the temperature range of the Sm
      C*A; (ii) the helix handedness inverts at both Sm C*-Sm C*A and Sm C*A-re-Sm C*
      phase transitions; (iii) the threshold electric field that is necessary to induce
      synclinic ordering in the Sm C*A phase decreases near both Sm C*A-Sm C* and Sm
      C*A-re-Sm C* phase boundaries. All these properties are properly described by a
      simple Landau model that accounts for nearest neighboring layer steric
      interactions and quadrupolar ordering only.

PMID- 11290103
TI  - Submicrometer resolution hard X-ray holography with the asymmetric bragg
      diffraction microscope.
AB  - The asymmetric Bragg diffraction microscope is a novel x-ray microscope which
      forms a magnified in-line near-field hologram by asymmetric reflection from two
      crossed flat crystals. In this paper, the optics of the microscope is studied
      theoretically. The optical transfer function is obtained, and the limiting
      spatial resolution, rated at 25% modulation transfer, is determined to be 0.30
      microm at an optimum magnification of 89x with Si crystals, over a wide range of
      hard x-ray wavelengths. Absorption and phase contrast images can be computed from
      holograms acquired at several object distances. Application to submicrometer
      resolution hard x-ray microtomography is envisioned.

PMID- 11290105
TI  - Monte Carlo simulation of growth of porous SiOx by vapor deposition.
AB  - A random network model containing defects has been developed and applied to the
      deposition of amorphous SiOx films on a flat substrate. A new Monte Carlo
      procedure enables dangling bonds to migrate and annihilate. The degree of
      porosity in the films is found to increase with oxygen content. As the oxygen
      content increases a larger fraction of pore surfaces is covered with oxygen, and
      the density of dangling bonds on pore surfaces decreases. Oxygen plays the role
      of a surfactant, lowering the energies of pore surfaces and enhancing the
      porosity of amorphous SiO2 compared to amorphous Si.

PMID- 11290106
TI  - Novel polygonized single-wall carbon nanotube bundles.
AB  - We have synthesized novel crystalline ropes of "polygonized" single-wall carbon
      nanotubes (SWCNTs). The tubes exhibit rounded-hexagonal cross sections in
      contrast to the earlier observations of nearly circular tubes. To investigate the
      structural characteristics of the lattice of SWCNTs we have performed extensive
      molecular-dynamics simulations. We find several metastable structures of the
      lattice characterized by different tube cross sections, hexagonal, rounded
      hexagonal, and circular, and increasing cell volume. The competition between
      different tube shapes as a function of tube diameter is analyzed and compared to
      experiments.

PMID- 11290107
TI  - Aggregation kinetics of thermal double donors in silicon.
AB  - A general kinetic model based on accurate density-functional-theoretic total
      energy calculations is introduced to describe the aggregation kinetics of oxygen
      related thermal double donors (TDD's) in silicon. The calculated kinetics, which
      incorporates the reactions of associations, dissociations, and isomerizations of
      all relevant oxygen complexes, is in agreement with experimental annealing
      studies. The aggregation of TDD's takes place through parallel-consecutive
      reactions where both mobile oxygen dimers and fast migrating chainlike TDD's
      capture interstitial oxygen atoms.

PMID- 11290108
TI  - Proof of the thermodynamical stability of the E' center in SiO2.
AB  - The E' center is a paradigmatic radiation-induced defect in SiO2 whose peculiar
      EPR and hyperfine activity has been known for over 40 years. This center has been
      traditionally identified with a distorted, positively charged oxygen vacancy
      V(+)O. However, no direct proof of the stability of this defect has ever been
      provided, so that its identification is still largely incomplete. Here we prove
      directly that distorted V(+)O is metastable and that it satisfies the key
      requirements for its identification as E', such as thermal and optical response,
      and activation-deactivation mechanisms.

PMID- 11290109
TI  - Novel gamma-phase of titanium metal at megabar pressures.
AB  - Group IV transition metals titanium, zirconium, and hafnium are expected to
      transform from an ambient hexagonal close packed (hcp, alpha-phase) to a body
      centered cubic (bcc, beta-phase) at high pressures. This transition path is
      usually facilitated by the occurrence of an intermediate hexagonal phase
      (distorted bcc, omega-phase). The existence of a bcc phase in zirconium and
      hafnium at high pressures has been known for the past ten years; however, its
      occurrence in titanium has been theoretically predicted but never observed. We
      report a novel unexpected transformation in titanium metal from an omega phase to
      an orthorhombic phase (distorted hcp, gamma-phase) at a pressure of 116+/-4 GPa.

PMID- 11290110
TI  - Probing impulsive strain propagation with X-ray pulses.
AB  - Pump-probe time-resolved x-ray diffraction of allowed and nearly forbidden
      reflections in InSb is used to follow the propagation of a coherent acoustic
      pulse generated by ultrafast laser excitation. The surface and bulk components of
      the strain could be simultaneously measured due to the large x-ray penetration
      depth. Comparison of the experimental data with dynamical diffraction simulations
      suggests that the conventional model for impulsively generated strain
      underestimates the partitioning of energy into coherent modes.

PMID- 11290111
TI  - Large harmonic softening of the phonon density of states of uranium.
AB  - Phonon density-of-states curves were obtained from inelastic neutron scattering
      spectra from the three crystalline phases of uranium at temperatures from 50 to
      1213 K. The alpha-phase showed an unusually large thermal softening of phonon
      frequencies. Analysis of the vibrational power spectrum showed that this phonon
      softening originates with the softening of a harmonic solid, as opposed to
      vibrations in anharmonic potentials. It follows that thermal excitations of
      electronic states are more significant thermodynamically than are the classical
      volume effects. For the alpha-beta and beta-gamma phase transitions, vibrational
      and electronic entropies were comparable.

PMID- 11290112
TI  - Kelvin waves cascade in superfluid turbulence.
AB  - We study numerically the interaction of four initial superfluid vortex rings in
      the absence of any dissipation or friction. We find evidence for a cascade of
      Kelvin waves generated by individual vortex reconnection events which transfers
      energy to higher and higher wave numbers k. After the vortex reconnections occur,
      the energy spectrum scales as k(-1) and the curvature spectrum becomes flat.
      These effects highlight the importance of Kelvin waves and reconnections in the
      transfer of energy within a turbulent vortex tangle.

PMID- 11290113
TI  - Atomically resolved local variation of the barrier height of the flip-flop motion
      of single buckled dimers of Si(100).
AB  - The dynamics of the flip-flop motion of single buckled dimers of Si(100) was
      elucidated by locating the tip of a scanning tunneling microscope over a single
      flip-flopping dimer and measuring the tunneling current (time trace). Based on a
      statistical analysis of the time trace, we succeeded in estimating the activation
      energy and the energy splitting between the two stable configurations of
      buckling. Strong dependence of the dynamics of the flip-flop motion on the local
      environment was found: Activation energy differs significantly (directly measured
      32 meV, estimated approximately 110 meV) for dimers in different domains.

PMID- 11290114
TI  - Evolution of two-dimensional wormlike nanoclusters on metal surfaces.
AB  - A pinch-off phenomenon is discovered in the evolution of 2D wormlike nanoclusters
      formed in homoepitaxial adlayers. This feature is shown to distinguish mass
      transport via periphery diffusion from other mechanisms. Continuum modeling of
      such evolution accurately describes experimental observations, particularly if
      one incorporates the anisotropy in step-edge line tension.

PMID- 11290115
TI  - Rate-equation approach to island capture zones and size distributions in
      epitaxial growth.
AB  - Understanding and predicting the effects of correlations between island size and
      the rate of monomer capture has been shown to be the central problem in
      predicting the island-size distribution in submonolayer growth. Here we summarize
      a method which involves a self-consistent coupling of evolution equations for the
      capture-zone distributions with rate equations for the island-size distribution.
      The method has been successfully applied to irreversible submonolayer growth in
      both one and two dimensions to predict the size-dependent capture numbers and
      island-size distributions.

PMID- 11290116
TI  - Electron addition spectrum in the supersymmetric t-J model with inverse-square
      interaction.
AB  - The electron addition spectrum A+(k,omega) is obtained analytically for the one
      dimensional (1D) supersymmetric t-J model with 1/r2 interaction. The result is
      obtained first for a small-sized system and its validity is checked against the
      numerical calculation. Then the general expression is found which is valid for
      arbitrary size of the system. The thermodynamic limit of A+(k,omega) has a simple
      analytic form with contributions from one spinon, one holon, and one antiholon
      all of which obey fractional statistics. The upper edge of A+(k,omega) in the
      (k,omega) plane includes a delta-function peak which reduces to that of the
      single-electron band in the low-density limit.

PMID- 11290117
TI  - Temperature-dependent fermi gap opening in the c(6x4)-C60/Ag(100) two-dimensional
      superstructure.
AB  - High-resolution angle-integrated photoemission of one monolayer of C (60)
      chemisorbed on Ag(100) shows the reversible opening of a gap at the Fermi level
      at temperatures 25< or =T< or =300 K. The gap reaches a maximum value of
      approximately 10 meV at T< or =70 K. This finding is the first evidence of an
      electronic phase transition in C60 monolayers and has implications on the ongoing
      debate about surface superconductivity in C60-based bulk materials.

PMID- 11290118
TI  - Composition-dependent electrical resistivity in an Al-Re-Si 1 /1-cubic
      approximant phase: an indication of electron confinement in clusters.
AB  - We report the synthesis of alpha-AlReSi and show that it is a 1/1-cubic
      approximant phase of the icosahedral quasicrystal with a = 12.9 A. The trend of
      the resistivity of the new approximant phase shows a nonmetallic character,
      similar to those seen in the stable icosahedral phases. The resistivity depends
      sensitively on the Re concentration and the nonmetallic transport is observed
      only at the Re concentration close to 17.4 at. %, where the transition metal
      sites in the icosahedral cluster are exclusively occupied by Re atoms. In view of
      a recent ab initio calculation, the present result suggests strongly the
      formation of the virtual bound states, or confinement of electrons, in the
      icosahedral clusters of transition metal atoms.

PMID- 11290119
TI  - High pressure insulator-metal transition in molecular fluid oxygen.
AB  - We report the first experimental evidence for a metallic phase in fluid molecular
      oxygen. Our electrical conductivity measurements of fluid oxygen under dynamic
      quasi-isentropic compression show that a nonmetal-metal transition occurs at 3.4
      fold compression, 4500 K, and 1.2 Mbar. We discuss the main features of the
      electrical conductivity dependence on density and temperature and give an
      interpretation of the nature of the electrical transport mechanisms in fluid
      oxygen at these extreme conditions.

PMID- 11290120
TI  - Frequency-dependent shot noise in long disordered superconductor-normal-metal
      superconductor contacts.
AB  - The shot noise in long diffusive superconductor-normal-metal-superconductor
      contacts is calculated using the semiclassical approach. At low frequencies and
      for purely elastic scattering, the voltage dependence of the noise is of the form
      S(I) = (4Delta+2eV)/3R. The electron-electron scattering suppresses the noise at
      small voltages resulting in vanishing noise yet infinite dS(I)/dV at V = 0. The
      distribution function of electrons consists of a series of steps, and the
      frequency dependence of noise exhibits peculiarities at omega = neV, omega = neV
      2Delta, and omega = 2Delta-neV for integer n.

PMID- 11290121
TI  - Wannier-Stark states of a quantum particle in 2D lattices.
AB  - A simple method of calculating the Wannier-Stark resonances in 2D lattices is
      suggested. Using this method we calculate the complex Wannier-Stark spectrum for
      a nonseparable 2D potential realized in optical lattices and analyze its general
      structure. The dependence of the lifetime of Wannier-Stark states on the
      direction of the static field (relative to the crystallographic axis of the
      lattice) is briefly discussed.

PMID- 11290122
TI  - Order-disorder transition in nanoscopic semiconductor quantum rings.
AB  - Using the path integral Monte Carlo technique we show that semiconductor quantum
      rings with up to six electrons exhibit a temperature, ring diameter, and particle
      number dependent transition between spin ordered and disordered Wigner crystals.
      Because of the small number of particles the transition extends over a broad
      temperature range and is clearly identifiable from the electron pair correlation
      functions.

PMID- 11290123
TI  - Persistent currents in mesoscopic connected rings.
AB  - We report measurements of the low temperature magnetic response of a line of 16
      GaAs/GaAlAs connected mesoscopic rings whose total length is much larger than
      l(straight phi). Using an on-chip micro-SQUID technology, we have measured a
      periodic response, with period h/e, corresponding to persistent currents in the
      rings of a typical amplitude of 0.40+/-0.08 nA per ring. Direct comparison with
      measurements on the same rings but isolated is presented.

PMID- 11290124
TI  - Current saturation and electrical breakdown in multiwalled carbon nanotubes.
AB  - We investigate the limits of high energy transport in multiwalled carbon
      nanotubes (MWNTs). In contrast to metal wires, MWNTs do not fail in the
      continuous, accelerating manner typical of electromigration. Instead, they fail
      via a series of sharp, equally sized current steps. We assign these steps to the
      sequential destruction of individual nanotube shells, consistent with the MWNT's
      concentric-shell geometry. Furthermore, the initiation of this failure is very
      sensitive to air exposure. In air failure is initiated by oxidation at a
      particular power, whereas in vacuum MWNTs can withstand much higher power
      densities and reach their full current carrying capacities.

PMID- 11290125
TI  - Surface transformation and photoinduced recovery in CdSe nanocrystals.
AB  - CdSe nanocrystals in solution and films can enter a metastable state in which the
      highly luminescent nanocrystals become dark. This change, which we attribute to a
      surface transformation, can be caused by heating or by changing the environment
      of the nanocrystals at room temperature. The metastable transformation is
      reversed upon illumination of above-band-gap light, at which point the
      nanocrystals are again highly luminescent.

PMID- 11290126
TI  - Vortex glass transition and quantum vortex liquid at low temperature in a thick a
      MoxSi1-x film.
AB  - We present measurements of ac complex resistivity, as well as dc resistivity, for
      a thick amorphous MoxSi1-x film at low temperatures ( T>0.04 K) in various
      constant fields B. We find that the vortex glass transition (VGT) persists down
      to T approximately 0.04Tc0 up to B approximately 0.9Bc2(0), where Tc0 and Bc2(0)
      are the mean-field transition temperature and upper critical field at T = 0,
      respectively. In the limit T-->0, the VGT line Bg(T) extrapolates to a field
      below Bc2(0), while the dc resistivity rho(T) tends to the finite nonzero value
      in fields just above Bg(0). These results indicate the presence of a metallic
      quantum vortex liquid at T = 0 in the regime Bg(0)<B<Bc2(0).

PMID- 11290127
TI  - Enhancement of the Josephson current by an exchange field in superconductor
      ferromagnet structures.
AB  - We calculate the dc Josephson current for two superconductor/ferromagnet (S/F)
      bilayers separated by a thin insulating film. It is demonstrated that the
      critical Josephson current I(c) in the junction strongly depends on the relative
      orientation of the effective exchange field h of the bilayers. We found that in
      the case of an antiparallel orientation I(c) increases at low temperatures with
      increasing h and at zero temperature has a singularity when h equals the
      superconducting gap Delta. This striking behavior contrasts with the suppression
      of the critical current by the magnetic moments aligned in parallel and is an
      interesting new effect of the interplay between superconductors and ferromagnets.

PMID- 11290128
TI  - Critical spin dynamics of the 2D quantum Heisenberg antiferromagnets Sr2CuO2Cl2
      and Sr2Cu3O4Cl2.
AB  - We report a neutron scattering study of the long-wavelength dynamic spin
      correlations in the model two-dimensional S = 1/2 square lattice Heisenberg
      antiferromagnets Sr2CuO2Cl2 and Sr2Cu3O4Cl2. The characteristic energy scale,
      omega(0)(T/J), is determined by measuring the quasielastic peak width in the
      paramagnetic phase over a wide range of temperature ( 0.2 less similarT/J less
      similar0.7). The obtained values for omega(0)(T/J) agree quantitatively between
      the two compounds and also with values deduced from quantum Monte Carlo
      simulations. The combined data show scaling behavior, omega approximately xi(-z),
      over the entire temperature range with z = 1.0(1), in agreement with dynamic
      scaling theory.

PMID- 11290129
TI  - Spin domains generate hierarchical ground state structure in J = +/-1 spin
      glasses.
AB  - Unbiased samples of ground states were generated for the short-range Ising spin
      glass with J(ij) = +/-1, in three dimensions. Clustering the ground states
      revealed their hierarchical structure, which is explained by correlated spin
      domains, serving as cores for macroscopic zero energy "excitations."

PMID- 11290130
TI  - Absolute spin magnetic moment of FeF2 from high energy photon diffraction.
AB  - The magnetic spin structure factor of FeF2 has been directly determined from high
      energy magnetic x-ray diffraction at 115 keV photon energy. A pure spin moment of
      mu = 4.01(5)mu(B) was observed, which agrees very well with the spin moment of
      the free Fe2+ ion and differs significantly from values of the total magnetic
      moment obtained by other methods. The magnetic phase transition of FeF2 has been
      carefully investigated and values for the critical exponent of the order
      parameter obtained by other techniques have been confirmed.

PMID- 11290131
TI  - Ferromagnetic phase transition in a Heisenberg fluid: Monte Carlo simulations and
      Fisher corrections to scaling.
AB  - The magnetic phase transition in a Heisenberg fluid is studied by means of the
      finite size scaling technique. We find that even for larger systems, considered
      in an ensemble with fixed density, the critical exponents show deviations from
      the expected lattice values similar to those obtained previously. This puzzle is
      clarified by proving the importance of the leading correction to the scaling that
      appears due to Fisher renormalization with the critical exponent equal to the
      absolute value of the specific heat exponent alpha. The appearance of such new
      corretions to scaling is a general feature of systems with constraints.

PMID- 11290132
TI  - 13C NMR chemical shift of single-wall carbon nanotubes.
AB  - We compute the magnetic shielding tensor within the London approximation and
      estimate the Knight shift of single-wall carbon nanotubes. Our results indicate
      that high resolution 13C NMR should be able to separate the metallic and
      insulator character of the nanotubes since a 11 ppm splitting is predicted from
      the respective resonances. As a model for disorder, bending, and defects in these
      structures, we investigate the magnetic response of nanotubes with finite size.
      We get a small line broadening coming from an intrinsic length dependent
      resonance effect. The nanotube packing is also studied and leads to a 20 ppm
      broadening which disappears under experimental high-resolution conditions.

PMID- 11290133
TI  - Two-photon resonant third-harmonic generation in La2CuO4.
AB  - Combining linear absorption and nonlinear third harmonic generation (THG)
      experiments, we investigate details of the electronic structure of the highly
      correlated electronic system in La2CuO4. We demonstrate strong THG mainly due to
      the charge transfer excitation from O (2p(sigma)) to Cu (3d(x2-y2)). The THG
      spectrum shows pronounced features due to three-photon and two-photon resonance
      enhancement as well as quantum interference effects. We obtain excellent
      agreement with a THG spectrum calculated in terms of the excitonic cluster model
      and can identify both odd and even symmetry excitation modes.

PMID- 11290134
TI  - Inhibition and enhancement of the spontaneous emission of quantum dots in
      structured microresonators.
AB  - Spontaneous emission of quantum dot systems in laterally structured microcavities
      that exhibit photon confinement in all three directions has been studied by time
      resolved photoluminescence spectroscopy. For on-resonance conditions, we find
      that the dot emission rate is increased substantially over that of the
      unstructured planar cavity. For off-resonance conditions, we are able to suppress
      the emission rate by an order of magnitude by using cavities with metal coatings,
      which we attribute to the suppression of leaky optical modes in these structures.

PMID- 11290135
TI  - Photon beats from a single semiconductor quantum dot.
AB  - Single-photon interference is observed on the ultranarrow long-term stable
      exciton resonance of an individual semiconductor quantum dot. This interference
      is related to the fine-structure splitting and allows direct conclusions about
      the coherence properties of the exciton. When selectively addressing a particular
      dot by quasiresonant phonon-assisted excitation, despite a rapid orientation
      relaxation on a 1-ps time scale, coherence is partly maintained. No significant
      further decoherence occurs when the ground state is reached until the exciton
      recombines radiatively (approximately 300 ps).

PMID- 11290136
TI  - State-specific enhancement of Cl+ and Cl- desorption for SiCl4 adsorbed on a
      Si(100) surface following Cl 2 p and Si 2 p core-level excitations.
AB  - State-specific desorption for SiCl4 adsorbed on a Si(100) surface at
      approximately 90 K with variable coverage following the Cl 2p and Si 2p core
      level excitations has been investigated using synchrotron radiation. The Cl+
      yields show a significant enhancement following the Cl 2p-->8a*1 excitation. The
      Cl- yields are notably enhanced at the 8a*1 resonance at both Cl 2p and Si 2p
      edges. The enhancement of the Cl- yield occurs through the formation of highly
      excited states of the adsorbed molecules. These results provide some new
      dissociation processes from adsorbates on surfaces via core-level excitation.

PMID- 11290137
TI  - Matter-wave entanglement and teleportation by molecular dissociation and
      collisions.
AB  - We propose dissociation of cold diatomic molecules as a source of atom pairs with
      highly correlated (entangled) positions and momenta, approximating the original
      quantum state introduced by Einstein, Podolsky, and Rosen (EPR) [Phys. Rev. 47,
      777 (1935)]. Wave packet teleportation is shown to be achievable by its collision
      with one of the EPR correlated atoms and manipulation of the other atom in the
      pair.

PMID- 11290138
TI  - Prediction of chaotic dynamics in sheared liquid crystalline polymers.
AB  - A rheological model for rodlike polymers in the nematic liquid-crystalline phase
      is analyzed to characterize irregular dynamical response under pure shear flows.
      The model is studied with a continuation approach, and a period doubling scenario
      is detected. Time series generated via simulation are studied with nonlinear
      analysis tools to prove the existence of chaotic regimes.

PMID- 11290139
TI  - Translocation of a confined polymer through a hole.
AB  - Based on an analogy between polymer translocation across a free energy barrier
      associated with polymer worming through a hole and classical nucleation and
      growth process, the escape time tau is predicted asymptotically to be
      N(N/rho)(1/3nu). N is the polymer length, rho is the monomer density prior to
      escape, and nu is the radius of gyration exponent. Monte Carlo simulation data
      collected in the high salt limit (nu approximately 3/5) are in agreement with the
      asymptotic law and provide vivid details of the escape.

PMID- 11290140
TI  - Dynamic concentration of motors in microtubule arrays.
AB  - We present experimental and theoretical studies of the dynamics of molecular
      motors in microtubule arrays and asters. By solving a convection-diffusion
      equation we find that the density profile of motors in a two-dimensional aster is
      characterized by continuously varying exponents. Simulations are used to verify
      the assumptions of the continuum model. We observe the concentration profiles of
      kinesin moving in quasi-two-dimensional artificial asters by fluorescent
      microscopy and compare with our theoretical results.

PMID- 11290141
TI  - Communication in networks with hierarchical branching.
AB  - We present a simple model of communication in networks with hierarchical
      branching. We analyze the behavior of the model from the viewpoint of critical
      systems under different situations. For certain values of the parameters, a
      continuous phase transition between a sparse and a congested regime is observed
      and accurately described by an order parameter and the power spectra. At the
      critical point the behavior of the model is totally independent of the number of
      hierarchical levels. Also scaling properties are observed when the size of the
      system varies. The presence of noise in the communication is shown to break the
      transition. The analytical results are a useful guide to forecasting the main
      features of real networks.

PMID- 11290142
TI  - Epidemic spreading in scale-free networks.
AB  - The Internet has a very complex connectivity recently modeled by the class of
      scale-free networks. This feature, which appears to be very efficient for a
      communications network, favors at the same time the spreading of computer
      viruses. We analyze real data from computer virus infections and find the average
      lifetime and persistence of viral strains on the Internet. We define a dynamical
      model for the spreading of infections on scale-free networks, finding the absence
      of an epidemic threshold and its associated critical behavior. This new
      epidemiological framework rationalizes data of computer viruses and could help in
      the understanding of other spreading phenomena on communication and social
      networks.

PMID- 11290145
TI  - Comment on "first-order amorphous-amorphous transformation in silica".

PMID- 11290143
TI  - Comment on "complete one-loop analysis of the nucleon's spin polarizabilities".

PMID- 11290147
TI  - Wetting of alkanes on water.

PMID- 11290148
TI  - Comment on "quantum phase transition of the randomly diluted Heisenberg
      antiferromagnet on a square lattice".

PMID- 11290150
TI  - Comment on "photonic band gaps: noncommuting limits and the 'acoustic band' ".

PMID- 11290152
TI  - Multimode dynamics of a coupled ultracold atomic-molecular system.
AB  - We analyze the coherent multimode dynamics of a system of coupled atomic and
      molecular Bose gases. Starting from an atomic Bose-Einstein condensate with a
      small thermal component, we observe a complete depletion of the atomic and
      molecular condensate modes on a short time scale due to a significant population
      of excited states. Giant coherent oscillations between the two condensates for
      typical parameters are almost completely suppressed. Our results cast serious
      doubts on the common use of the 2-mode model for the description of coupled
      ultracold atomic-molecular systems and should be considered when planning future
      experiments with ultracold molecules.

PMID- 11290153
TI  - Bose-Einstein condensates in standing waves: the cubic nonlinear Schrodinger
      equation with a periodic potential.
AB  - We present a new family of stationary solutions to the cubic nonlinear
      Schrodinger equation with an elliptic function potential. In the limit of a
      sinusoidal potential our solutions model a quasi-one-dimensional dilute gas Bose
      Einstein condensate trapped in a standing light wave. Provided that the ratio of
      the height of the variations of the condensate to its dc offset is small enough,
      both trivial phase and nontrivial phase solutions are shown to be stable. Recent
      developments allow for experimental investigation of these predictions.

PMID- 11290154
TI  - Intermittent implosion and pattern formation of trapped Bose-Einstein condensates
      with an attractive interaction.
AB  - The collapsing dynamics of a trapped Bose-Einstein condensate with attractive
      interaction are revealed to exhibit two previously unknown phenomena. During the
      collapse, the condensate undergoes a series of rapid implosions that occur
      intermittently within a very small region. When the sign of the interaction is
      suddenly switched from repulsive to attractive, e.g., by the Feshbach resonance,
      density fluctuations grow to form various patterns such as a shell structure.

PMID- 11290155
TI  - Sound emission due to superfluid vortex reconnections.
AB  - By performing numerical simulations based on the Gross-Pitaevskii equation, we
      make direct quantitative measurements of the sound energy released due to
      superfluid vortex reconnections. We show that the energy radiated expressed in
      terms of the loss of vortex line length is a simple function of the reconnection
      angle. In addition, we study the temporal and spatial distribution of the
      radiation and show that energy is emitted in the form of a sound pulse with a
      wavelength of a few healing lengths.

PMID- 11290156
TI  - Knots and random walks in vibrated granular chains.
AB  - We study experimentally statistical properties of the opening times of knots in
      vertically vibrated granular chains. Our measurements are in good qualitative and
      quantitative agreement with a theoretical model involving three random walks
      interacting via hard-core exclusion in one spatial dimension. In particular, the
      knot survival probability follows a universal scaling function which is
      independent of the chain length, with a corresponding diffusive characteristic
      time scale. Both the large-exit-time and the small-exit-time tails of the
      distribution are suppressed exponentially, and the corresponding decay
      coefficients are in excellent agreement with theoretical values.

PMID- 11290157
TI  - Submillimeter test of the gravitational inverse-square law: a search for "large"
      extra dimensions.
AB  - Motivated by higher-dimensional theories that predict new effects, we tested the
      gravitational 1/r(2) law at separations ranging down to 218 microm using a 10
      fold symmetric torsion pendulum and a rotating 10-fold symmetric attractor. We
      improved previous short-range constraints by up to a factor of 1000 and find no
      deviations from Newtonian physics.

PMID- 11290158
TI  - Gravitationally bound monopoles.
AB  - We construct monopole solutions in SU(2) Einstein-Yang-Mills-Higgs theory
      carrying magnetic charge n. For vanishing and small Higgs self-coupling, these
      multimonopole solutions are gravitationally bound. Their mass per unit charge is
      lower than the mass of the n = 1 monopole. For large Higgs self-coupling only a
      repulsive phase exists.

PMID- 11290159
TI  - Black hole thermodynamics from calculations in strongly coupled gauge theory.
AB  - We develop an approximation scheme for the quantum mechanics of N D0-branes at
      finite temperature in the 't Hooft large- N limit. The entropy of the quantum
      mechanics calculated using this approximation agrees well with the Bekenstein
      Hawking entropy of a ten-dimensional nonextremal black hole with 0-brane charge.
      This result is in accordance with the duality conjectured by Itzhaki, Maldacena,
      Sonnenschein, and Yankielowicz [Phys. Rev. D 58, 046004 (1998)]. Our
      approximation scheme provides a model for the density matrix which describes a
      black hole in the strongly coupled quantum mechanics.

PMID- 11290160
TI  - Neutrinos produced by ultrahigh-energy photons at high redshift.
AB  - Some of the proposed explanations for the origin of ultrahigh-energy cosmic rays
      invoke new sources of energetic photons (e.g., topological defects, relic
      particles, etc.). At high redshift, when the cosmic microwave background has a
      higher temperature but the radio background is low, the ultrahigh-energy photons
      can generate neutrinos through pair production of muons and pions. The resulting
      diffuse background of 10(17) eV neutrinos can be detected by future experiments.

PMID- 11290161
TI  - Constraints on galaxy bias, matter density, and primordial non-Gaussianity from
      the PSCz galaxy redshift survey.
AB  - We compute the bispectrum for the IRAS PSCz catalog and find that the galaxy
      distribution displays the characteristic signature of gravity. Assuming Gaussian
      initial conditions, we obtain galaxy biasing parameters 1/b(1) = 1.20(+0.18)(
      0.19) and b(2)/b(2)(1) = -0.42+/-0.19, with no sign of scale-dependent bias for k
      < or = 0.3h Mpc(-1). These results impose stringent constraints on non-Gaussian
      initial conditions. For dimensional scaling models with chi(2)(N) statistics, we
      find N > 49, which implies a constraint on primordial skewness B3 < 0.35.

PMID- 11290162
TI  - 't Hooft loop in SU(2) Yang-Mills theory.
AB  - We study the behavior of the spatial and temporal 't Hooft loop at zero and
      finite temperature in the 4D SU(2) Yang-Mills theory, using a new numerical
      method. In the deconfined phase T > T(c), the spatial 't Hooft loop exhibits a
      dual string tension, which vanishes at T(c) with a 3D Ising-like critical
      exponent.

PMID- 11290163
TI  - h --> mutau at Hadron colliders.
AB  - We study the observability for a lepton flavor-changing decay of a Higgs boson h-
      > mutau at Hadron colliders. Flavor-changing couplings of a Higgs boson exist at
      tree level in models with multiple Higgs doublets. The hmutau coupling is
      particularly motivated by the favorable interpretation of nu(mu)-nu(tau)
      oscillation. We find that at the Tevatron run II the unique mutau signature could
      serve as the Higgs discovery channel, surpassing expectations for Higgs boson
      searches in the SM and in a large parameter region of the MSSM. The sensitivity
      will be greatly improved at the LHC, beyond the coverage at a muon collider Higgs
      factory.

PMID- 11290164
TI  - Towards a solution of the charmonium production controversy: k( perpendicular)
      factorization versus color-octet mechanism.
AB  - The cross section of chi(cJ) hadroproduction is calculated in the k(
      perpendicular)-factorization approach. We find a significant contribution of the
      chi(c1) state due to non-applicability of the Landau-Yang theorem because of off
      shell gluons. The results are in agreement with data and, in contrast to the
      collinear factorization, show a dominance of the color-singlet part and a strong
      suppression of the color octet contribution. Our results could therefore lead to
      a solution of the long-standing controversy between the color-singlet model and
      the color-octet mechanism.

PMID- 11290165
TI  - Prompt alpha decay of a well-deformed band in (58)Ni.
AB  - Two excited well-deformed bands have been observed in the semi-magic nucleus
      (58)Ni. One of the bands was observed to partially decay by emission of a prompt
      discrete alpha particle that feeds the 2949 keV 6(+) spherical yrast state in the
      daughter nucleus (54)Fe. This constitutes the first observation of prompt alpha
      emission from states lying in the deformed secondary minimum of the nuclear
      potential. gamma-ray linking transitions via several parallel paths establish the
      spin, parity, and excitation energy of this deformed band in (58)Ni.

PMID- 11290166
TI  - Precise half-life measurement for the superallowed 0(+)-->0(+) beta emitter
      (74)Rb: first results from the new radioactive beam facility (ISAC) at TRIUMF.
AB  - Presently, the world data for superallowed beta decay leads to a result in
      disagreement (at the 98% confidence level) with the predictions of the minimal
      standard model for the unitarity of the Cabibbo-Kobayashi-Maskawa matrix. Precise
      data for the superallowed 0(+)-->0(+) beta decay of (74)Rb would provide a
      critical test of the nucleus-dependent isospin symmetry-breaking corrections that
      must be calculated for these superallowed Fermi beta decays. The present work
      reports the first precise measurement of the half-life for (74)Rb ( t(1/2) =
      64.761+/-0.031 ms). The data were obtained at the radioactive beam facility
      (ISAC) at TRIUMF using a beam of approximately 4000 (74)Rb ions s(-1).

PMID- 11290167
TI  - Rotational bands in the proton emitter (141)Ho.
AB  - Rotational bands feeding the ground state and the isomeric state in the proton
      emitter (141)Ho were observed using the recoil-decay tagging method. This
      constitutes direct evidence that (141)Ho is deformed. A quadrupole deformation of
      beta(2) = 0.25(4) was deduced for the ground state from the extracted dynamic
      moment of inertia. Based on observed band crossings and signature splittings the
      7/2(-)[523] and 1/2(+)[411] configurations were proposed for the ground state and
      the isomeric state, respectively. Comparison with particle-rotor calculations for
      beta(2) = 0.25 indicates, however, that (141)Ho may have significant hexadecapole
      deformation and could be triaxial in the 7/2(-)[523] ground state.

PMID- 11290168
TI  - Two-wire waveguide and interferometer for cold atoms.
AB  - A versatile miniature de Broglie waveguide is formed by two parallel current
      carrying wires in the presence of a uniform bias field. We derive a variety of
      analytical expressions to describe the guide and present a quantum theory to show
      that it offers a remarkable range of possibilities for atom manipulation on the
      submicron scale. These include controlled and coherent splitting of the wave
      function as well as cooling, trapping, and guiding. In particular, we discuss a
      novel microscopic atom interferometer with the potential to be exceedingly
      sensitive.

PMID- 11290169
TI  - Lifetime measurements of metastable states in Fe+.
AB  - The lifetime of two metastable levels in Fe+ has been measured by laser probing
      of a stored ion beam. In the dense spectrum of Fe+, the metastable levels a
      (6)S(5/2) and b (4)D(7/2) were selected and their lifetimes were determined to be
      230 +/- 30 and 530 +/- 30 ms, respectively. The lifetimes are compared with
      previous theoretical results. Metastable lifetime measurements of Fe+ are of
      great importance for interpretation of spectra from astronomical objects. The
      present experiment opens for the possibilities to investigate lifetimes of
      metastable states in complex atomic ions, which have, so far, been unexplored.

PMID- 11290170
TI  - Experimental observation of post-collision interaction and interference effects
      in resonant double photoionization processes.
AB  - The combined effects of post-collision interaction in the final state and
      interference due to the indistinguishability of the two electrons have been
      studied in a selected case of resonant double photoionization of neon. In our
      coincidence experiments, the photo- and Auger-electron pair was measured when the
      two electrons have nearly equal energy and are ejected at small mutual angle. The
      obtained energy distributions exhibit a strong interplay of post-collision
      interaction and interference effects, in agreement with the theoretical
      prediction of Sheinerman and Schmidt [J. Phys. B 30, 1677 (1997)] made on
      beryllium.

PMID- 11290171
TI  - Manipulation of cold atomic collisions by cavity QED effects.
AB  - We show how the dynamics of collisions between cold atoms can be manipulated by a
      modification of spontaneous emission times. This is achieved by placing the
      atomic sample in a resonant optical cavity. Spontaneous emission is enhanced by a
      combination of multiparticle entanglement together with a higher density of modes
      of the modified vacuum field, in a situation akin to superradiance. A specific
      situation is considered and we show that this effect can be experimentally
      observed as a large suppression in trap-loss rates.

PMID- 11290172
TI  - Observation of completely destructive quantum interference between interacting
      resonances in molecular predissociation.
AB  - A unique observation is presented of interacting predissociating resonances which
      exhibit completely destructive interference in a region between the resonances.
      The use of a double-resonance technique, in which single rotational levels of the
      b (1)Sigma(+)(g) state of O2, prepared by pumping the magnetic-dipole b <--X
      transition, are probed by (2+1) resonance-enhanced multiphoton-ionization
      spectroscopy, eliminates overlapping rotational structure and enables observation
      of the interference process. Using a diabatic coupled-channel model, the
      interacting resonances are shown to be derived from the d (1)Pi(g)(v = 3,J = 17)
      Rydberg and II (1)Delta(g)(v = 6,J = 17) valence states.

PMID- 11290173
TI  - Giant Barkas effect observed for light ions channeling in Si.
AB  - Measurements of the electronic energy loss are presented for (4)He and (7)Li ions
      channeling along the Si main axial directions at intermediate to high projectile
      energies. The Barkas effect, an energy-loss enhancement proportional to the third
      power of the projectile charge at high energies, is clearly separated from other
      processes. It reaches about 50% for Li ions channeling along the Si [110]
      direction. The observed Barkas contribution from the valence-electron gas is in
      fair agreement with the Lindhard model.

PMID- 11290174
TI  - Resolution of the frozen-charge paradox in stopping of channeled heavy ions.
AB  - The long-standing problem of the lacking signature of a Barkas effect in the
      stopping of swift heavy ions under channeling conditions has been analyzed
      theoretically. The stopping model provides explicit dependences on impact
      parameter and allows for projectile screening and higher-order Z(1) corrections.
      The analysis differentiates between principal target shells. A distinct Barkas
      correction is found in accordance with standard theory. It is less pronounced for
      channeled than for random stopping because of the dominance of outer target
      shells. Varying contributions from different target shells to the stopping force
      may give rise to an inversion of the commonly observed variation with ion energy
      and charge state of the Barkas correction.

PMID- 11290175
TI  - Two-photon evanescent-volume wave spectroscopy: a new account of gas-solid
      dynamics in the boundary layer.
AB  - A novel type of laser spectroscopy for the investigation of the collisional
      dynamics of atoms in the close vicinity of a surface has been developed. The
      technique utilizes excitation of the vapor atoms in two crossed laser fields, one
      of which is directed normally to the surface, whereas the other one excites an
      evanescent wave propagating along the surface. The results, obtained for sodium
      atoms near a dielectric prism surface, are quantitatively reproduced by a
      rigorous theoretical approach. This new, nonintrusive method allows one to
      distinguish by pure optical means between different groups of atoms and to
      extract their two-dimensional velocity distributions.

PMID- 11290176
TI  - Excitation of molecular vibrations by positron impact.
AB  - Absolute cross sections for the vibrational excitation of CO, CO2, and H2 by
      positron impact are presented for incident positron energies from 0.5 eV to
      several electron volts. The measurements use a novel technique that exploits the
      adiabatic motion of a positron beam in a strong magnetic field. This work is the
      first systematic experimental study of vibrational excitation by positron impact,
      and extends to energies where positron measurements have traditionally been
      difficult. The measured cross sections are compared with available theoretical
      calculations.

PMID- 11290177
TI  - O(alpha(3) lnalpha) corrections to muonium and positronium hyperfine splitting.
AB  - We compute O(alpha(3)lnalpha) relative corrections to the ground-state hyperfine
      splitting of a QED two-body bound state with different masses of constituents.
      The general result is then applied to muonium and positronium. In particular, a
      new value of the muon-to-electron mass ratio is derived from the muonium ground
      state hyperfine splitting.

PMID- 11290178
TI  - Triggered single photons from a quantum dot.
AB  - We demonstrate a new method for generating triggered single photons. After a
      laser pulse generates excitons inside a single quantum dot, electrostatic
      interactions between them and the resulting spectral shifts allow a single
      emitted photon to be isolated. Correlation measurements show a reduction of the
      two-photon probability to 0.12 times the value for Poisson light. Strong
      antibunching persists when the emission is saturated. The emitted photons are
      also polarized.

PMID- 11290179
TI  - Fractality of the hydrodynamic modes of diffusion.
AB  - Transport by normal diffusion can be decomposed into hydrodynamic modes which
      relax exponentially toward the equilibrium state. In chaotic systems with 2
      degrees of freedom, the fine scale structures of these modes are singular and
      fractal, characterized by a Hausdorff dimension given in terms of Ruelle's
      topological pressure. For long-wavelength modes, we relate the Hausdorff
      dimension to the diffusion coefficient and the Lyapunov exponent. This
      relationship is tested numerically on two Lorentz gases, one with hard repulsive
      forces, the other with attractive, Yukawa forces. The agreement with theory is
      excellent.

PMID- 11290180
TI  - Generalized splay state in coupled chaotic oscillators induced by weak mutual
      resonant interactions.
AB  - Dynamic behavior of coupled chaotic oscillators is investigated. A transition
      from high-dimensional hyperchaos to a generalized periodic splay state is found
      for extremely weak coupling. Chaotic nature of a single oscillator and mutual
      resonant interactions are regarded to be responsible for this self-organized
      ordering. The functional phase distribution of the generalized splay state, which
      is essentially different from the equal-phase-separation distribution of the
      conventional splay states, can be well predicted by analyzing a single
      periodically forced oscillator.

PMID- 11290181
TI  - Optical billiards for atoms.
AB  - One of the central paradigms for classical and quantum chaos in conservative
      systems is the two-dimensional billiard in which particles are confined to a
      closed region in the plane, undergoing elastic collisions with the walls and free
      motion in between. We report the first realization of billiards using ultracold
      atoms bouncing off beams of light. These beams create the desired spatial
      pattern, forming an "optical billiard." We find excellent agreement between
      theory and our experimental demonstration of chaotic and stable motion in optical
      billiards, establishing a new testing ground for classical and quantum chaos.

PMID- 11290182
TI  - Observation of chaotic and regular dynamics in atom-optics billiards.
AB  - We report on experimental observations of chaotic and regular motion of ultracold
      atoms confined by a billiard-shaped optical dipole potential induced by a rapidly
      scanning laser beam. To investigate the dynamics of the atoms confined by such an
      "atom-optics" billiard we measure the decay of the number of trapped atoms
      through a hole on the boundary. A fast and purely exponential decay, the clear
      signature of chaotic motion, is found for a stadium billiard, but not for a
      circular or an elliptical billiard, in agreement with theory. We also
      investigated the effects of decoherence, velocity spread, and gravity on regular
      and chaotic motion.

PMID- 11290183
TI  - Dynamics of a random laser above threshold.
AB  - We have performed enhanced backscattering experiments in a high gain random
      laser, under circumstances where a stationary theory predicts the laser intensity
      to diverge. Above the laser threshold the observed backscatter cone changes only
      gradually, not showing any signs of the divergence. We present measurements and
      theory-generalized laser equations with a diffusive transport term for pump and
      laser light-to explain the observed behavior. The population dynamics prevent an
      indefinite growth of the intensity. Time dependence is essential for a theory of
      random lasers above the laser threshold.

PMID- 11290184
TI  - Optical trirefringence in photonic crystal waveguides.
AB  - We demonstrate that 2D photonic crystals can possess optical trirefringence in
      which there are six field orientations for which linear incident light is not
      perturbed on reflection or transmission. Such a property is rigorously forbidden
      in homogeneous nonmagnetic dielectrics which can possess only optical
      birefringence. We experimentally demonstrate this phenomena in silicon-based
      mesostructures formed from photonic crystal waveguides embedded in a Fabry-Perot
      cavity. Multirefringence is controlled by the presence of submicron dielectric
      patterning and is well explained by an exact scattering matrix theory.

PMID- 11290185
TI  - Long-pulse improved central electron confinement in the TCV tokamak with electron
      cyclotron heating and current drive.
AB  - Current profile tailoring by electron cyclotron heating (ECH) and current drive
      (ECCD) is used to improve central electron energy confinement in the TCV tokamak.
      Counter-ECCD on axis alone achieves this goal in a transient manner only. A
      stable scenario is obtained by a two-step sequence of off-axis ECH, which
      stabilizes magnetohydrodynamics modes, and on-axis counter-ECCD, which generates
      a flat or inverted current profile. This high-confinement regime, with central
      temperatures up to 9 keV (at a normalized beta(N) approximately 0.6), has been
      sustained for the entire duration of the heating pulse, or over 200 electron
      energy confinement times and 5 current redistribution times.

PMID- 11290186
TI  - Complex gamma-ray hologram: solution to twin images problem in atomic resolution
      imaging.
AB  - A new technique for high fidelity three-dimensional imaging of atomic structure
      with gamma-ray holography is demonstrated. A complex hologram was constructed
      from holograms recorded for different values of the nuclear scattering amplitude
      on both sides of the (57)Fe Mossbauer resonance. The holographic reconstruction
      was applied to this complex hologram resulting in a twin-image-free image of the
      bcc Fe local structure. The proposed procedure allows the removal of the twin
      images for all real space, making gamma-ray holography an unambiguous tool for
      atomic and magnetic structure imaging.

PMID- 11290187
TI  - Pairing interactions and Gibbs adsorption at the liquid bi-in surface: a resonant
      X-ray reflectivity study.
AB  - Resonant x-ray reflectivity measurements from the surface of liquid Bi(22)In(78)
      find only a modest surface Bi enhancement, with 35 at. % Bi in the first atomic
      layer. This is in contrast to the Gibbs adsorption in all liquid alloys studied
      to date, which show surface segregation of a complete monolayer of the low
      surface tension component. This suggests that surface adsorption in Bi-In is
      dominated by attractive interactions that increase the number of Bi-In neighbors
      at the surface. These are the first measurements in which resonant x-ray
      scattering has been used to quantify compositional changes induced at a liquid
      alloy surface.

PMID- 11290188
TI  - Chemical ordering in Al(72)Ni(20)Co(8) decagonal quasicrystals.
AB  - First-principles total energy calculations of the 2-nm clusters seen in high
      perfection Al (72)Ni(20)Co(8) decagonal quasicrystals demonstrate that chemical
      ordering between Al and transition metals in the central ring is energetically
      highly favorable. The chemical ordering introduces extensive structure relaxation
      and results in broken decagonal symmetry. Such broken symmetry is sufficient to
      enforce the perfect quasiperiodic tiling.

PMID- 11290189
TI  - Calculation of quantum tunneling for a spatially extended defect: the dislocation
      kink in copper has a low effective mass.
AB  - Several experiments indicate that there are atomic tunneling defects in
      plastically deformed metals. How this is possible has not been clear, given the
      large mass of the metal atoms. Using a classical molecular-dynamics calculation,
      we determine the structures, energy barriers, effective masses, and quantum
      tunneling rates for dislocation kinks and jogs in copper screw dislocations. We
      find that jogs are unlikely to tunnel, but the kinks should have large quantum
      fluctuations. The kink motion involves hundreds of atoms each shifting a tiny
      amount, leading to a small effective mass and tunneling barrier.

PMID- 11290190
TI  - Convective Cahn-Hilliard models: from coarsening to roughening.
AB  - In this paper we demonstrate that convective Cahn-Hilliard models, describing
      phase separation of driven systems (e.g., faceting of growing thermodynamically
      unstable crystal surfaces), exhibit, with the increase of the driving force, a
      transition from the usual coarsening regime to a chaotic behavior without
      coarsening via a pattern-forming state characterized by the formation of various
      stationary and traveling periodic structures as well as structures with localized
      oscillations. Relation of this phenomenon to a kinetic roughening of
      thermodynamically unstable surfaces is discussed.

PMID- 11290191
TI  - Surface vibrational spectroscopic study of surface melting of ice.
AB  - Surface melting on the (0001) face of hexagonal ice ( I(h)) was studied by sum
      frequency vibrational spectroscopy in the OH stretch frequency range. The degree
      of orientational order of the dangling OH bonds at the surface was measured as a
      function of temperature. Disordering sets in around 200 K and increases
      dramatically with temperature. The results show that the disordered (quasiliquid)
      layer on ice is structurally different from normal liquid water.

PMID- 11290192
TI  - Superfluid fraction of (3)He-(4)He mixtures confined at 0.0483 microm between
      silicon wafers.
AB  - We report measurements of the superfluid fraction rho(s)/rho of films of (3)He
      (4)He mixtures confined between silicon wafers at 0.0483 microm separation. The
      data obtained using adiabatic fountain resonance (AFR) can be used to test for
      the first time expectations of correlation-length scaling in the case of planar
      mixtures. For the mixtures, the data for rho(s)/rho collapse well on a universal
      function. The dissipation associated with AFR can also be scaled, and indicates
      two-dimensional crossover. These results are in contrast to pure (4)He, where
      over a wider range of confinements, the data for rho(s)/rho are found not to
      scale.

PMID- 11290193
TI  - Nothing moves a surface: vacancy mediated surface diffusion.
AB  - We report scanning tunneling microscopy observations, which imply that all atoms
      in a Cu(001) surface move frequently, even at room temperature. Using a low
      density of embedded indium "tracer" atoms, we visualize the diffusive motion of
      surface atoms. Surprisingly, the indium atoms seem to make concerted, long jumps.
      Responsible for this motion is an ultralow density of surface vacancies,
      diffusing rapidly within the surface. This interpretation is supported by a
      detailed analysis of the displacement distribution of the indium atoms, which
      reveals a shape characteristic for the vacancy mediated diffusion mechanism that
      we propose.

PMID- 11290194
TI  - Novel surface vibrational spectroscopy: infrared-infrared-visible sum-frequency
      generation.
AB  - A novel type of surface vibrational sum-frequency generation spectroscopy is
      presented that enables a highly specific measurement of the coupling of molecules
      on surfaces. With this doubly vibrationally resonant technique, two-dimensional
      vibrational spectroscopy of molecules on surfaces becomes possible. The technique
      is demonstrated for the C-O stretch vibration of CO on a ruthenium (001) surface.
      It allows for the determination of the intermolecular coupling strength of dipole
      coupled CO molecules on the surface.

PMID- 11290195
TI  - Difference in the dynamic scaling behavior of droplet size distribution for
      coalescence under pulsed and continuous vapor delivery.
AB  - Dynamic scaling behavior of the droplet size distribution in the coalescence
      regime for growth by pulsed laser deposition is studied experimentally and by
      computer simulation, and the same is compared with that for continuous vapor
      deposition. The scaling exponent for pulsed deposition is found to be (1.2 +/-
      0.1), which is significantly lower as compared to that for continuous deposition
      (1.6 +/- 0.1). Simulations reveal that this dramatic difference can be traced to
      the large fraction of multiple droplet coalescence under pulsed vapor delivery. A
      possible role of the differing diffusion fields in the two cases is also
      suggested.

PMID- 11290196
TI  - Simple analytical particle and kinetic energy densities for a dilute fermionic
      gas in a d-dimensional harmonic trap.
AB  - We derive simple analytical expressions for the particle density rho(r) and the
      kinetic energy density tau(r) for a system of noninteracting fermions in a d
      dimensional isotropic harmonic oscillator potential. We test the Thomas-Fermi
      (TF, or local-density) approximation for the functional relation tau[rho] using
      the exact rho(r) and show that it locally reproduces the exact kinetic energy
      density tau(r), including the shell oscillations, surprisingly well everywhere
      except near the classical turning point. For the special case of two dimensions
      (2D), we obtain the unexpected analytical result that the integral of
      tau(TF)[rho(r)] yields the exact total kinetic energy.

PMID- 11290197
TI  - Anomalous temperature dependence of the magnetic field induced antiferromagnetic
      moment in the antiferroquadrupolar ordered state of CeB6.
AB  - The magnetic field induced antiferromagnetic moment M(AF) at low magnetic fields
      in the antiferroquadrupolar (AFQ) ordered phase of CeB6 was investigated by
      elastic neutron diffraction experiments for H parallel [110]. The peak intensity
      at the AF magnetic reciprocal point (1 / 2,1 / 2,1 / 2) corresponding to M(2)(AF)
      increases with decreasing temperature below the AFQ ordering temperature T(Q),
      and exhibits a broad maximum at T approximately 3 K and decreases with a further
      decrease of temperature. This unusual behavior of M(AF) at low fields is
      explained as a result of the competition between the AF-octupolar and AF-exchange
      interactions in the O(xy) type AFQ ordered state.

PMID- 11290198
TI  - Local density of states of a three-dimensional conductor in the extreme quantum
      limit.
AB  - The electronic structure of the narrow gap semiconductor InAs is investigated by
      scanning tunneling spectroscopy and magnetotransport measurements in the extreme
      quantum limit. The well-known oscillations of the Hall coefficient are reproduced
      and the last, most pronounced oscillation is shown to be correlated with the
      appearance of corrugations in the local density of states. While the increasing
      part of the Hall constant corresponds to the existence of isolated patterns
      indicating magnetic field induced localization, the decreasing part correlates
      with the development of a network which most likely consists of one-dimensional
      channels. We conclude that the decrease of the Hall constant in the extreme
      quantum limit is caused by a transition from a purely three-dimensional to a
      partly one-dimensional transport regime.

PMID- 11290199
TI  - Field-induced dynamic diamagnetism in a charge-density-wave system.
AB  - ac susceptibility measurements of the charge-density-wave (CDW) compound alpha
      (BEDT-TTF)(2)-KHg(SCN)(4) at magnetic fields, mu0H >23 T, above its Pauli
      paramagnetic limit, reveal unambiguously that the magnetic hysteresis observed
      previously within this CDW phase is diamagnetic and can only be explained by
      induced currents. It is argued that the ensemble of experimental techniques
      amounts to a strong case for dissipationless conductivity within this phase.

PMID- 11290200
TI  - Electrodynamic dip in the local density of states of a metallic wire.
AB  - We have measured the differential conductance of a tunnel junction between a thin
      metallic wire and a thick ground plane, as a function of the applied voltage. We
      find that near zero voltage, the differential conductance exhibits a dip, which
      scales as 1/square root of [V] down to voltages V approximately 10k(B)T/e. The
      precise voltage and temperature dependence of the differential conductance is
      accounted for by the effect on the tunneling density of states of the macroscopic
      electrodynamics contribution to electron-electron interaction, and not by the
      short-ranged screened-Coulomb repulsion at microscopic scales.

PMID- 11290201
TI  - Diamagnetic persistent current in diffusive normal-metal rings.
AB  - We have measured a diamagnetic persistent current with flux periodicities of both
      h/e and h/2e in an array of thirty diffusive mesoscopic gold rings. At the lowest
      temperatures, the magnitudes of the currents per ring corresponding to the h/e-
      and h/2e-periodic responses are both comparable to the Thouless energy E(c)
      identical with Planck's over 2pi/tau(D), where tau(D) is the diffusion time.
      Taken in conjunction with earlier experiments, our results strongly challenge the
      conventional theories of persistent current. We consider a new approach
      associated with the saturation of the phase coherence time tau(phi).

PMID- 11290202
TI  - Two-component interference effect: model of a spin-polarized transport.
AB  - The effect of spin-involved interaction on the transport properties of disordered
      two-dimensional electron systems with ferromagnetic contacts is described using a
      two-component model. Components representing spin-up and spin-down states are
      supposed to be coupled at a discrete set of points. We have found that due to the
      additional interference arising in two-component systems the difference between
      conductances for the parallel and antiparallel orientations of the contact
      magnetization changes its sign as a function of the length of the conducting
      channel.

PMID- 11290203
TI  - Paramagnetic reentrant effect in mesoscopic cylinders made of a normal metal in
      proximity with a superconductor.
AB  - We show that the paramagnetic reentrant effect observed in experiments by Mota et
      al. in mesoscopic cylinders made of a normal metal in proximity with a
      superconductor, can be caused by paramagnetic persistent currents flowing on the
      outer shell of the cylinder.

PMID- 11290204
TI  - Phase fluctuations and the pseudogap in YBa(2)Cu(3)O (x).
AB  - The thermodynamics of the superconducting transition is studied as a function of
      doping using high-resolution expansivity data of YBa(2)Cu(3)O (x) single crystals
      and Monte Carlo simulations of the anisotropic 3D- XY model. We directly show
      that T(c) of underdoped YBa(2)Cu(3)O (x) is strongly suppressed from its mean
      field value (T(MF)(c)) by phase fluctuations of the superconducting order
      parameter. For overdoped YBa(2)Cu(3)O (x) fluctuation effects are greatly reduced
      and T(c) approximately T(MF)(c). We find that T(MF)(c) exhibits a similar doping
      dependence as the pseudogap energy, naturally suggesting that the pseudogap
      arises from phase-incoherent Cooper pairing.

PMID- 11290205
TI  - Resonant spin excitation in an overdoped high temperature superconductor.
AB  - An inelastic neutron scattering study of overdoped Bi(2)Sr(2)CaCu(2)O(8+delta) (
      T(c) = 83 K) has revealed a resonant spin excitation in the superconducting
      state. The mode energy is E(res) = 38.0 meV, significantly lower than in
      optimally doped Bi(2)Sr(2)CaCu(2)O(8+delta) ( T(c) = 91 K, E(res) = 42.4 meV).
      This observation, which indicates a constant ratio E(res)/k(B)T(c) approximately
      5.4, helps resolve a long-standing controversy about the origin of the resonant
      spin excitation in high temperature superconductors.

PMID- 11290206
TI  - Anomalous peak in the superconducting condensate density of cuprate high- T(c)
      superconductors at a unique doping state.
AB  - The doping dependence of the ratio of the superconducting condensate density to
      the effective mass, n(o)(s)/m(*)(ab), was studied in detail by muon-spin rotation
      for Y(0.8)Ca(0.2)Ba(2)(Cu(1-z)Zn(z))(3)O(7-delta) and Tl(0.5-y)Pb(0.5+y)Sr(2)Ca(1
      x)Y(x)Cu(2)O(7). Our data show that n(o)(s)/m(*)(ab) exhibits a peak at a unique
      doping state in the overdoped regime. Its position coincides with the critical
      doping state, where the normal state pseudogap was reported to appear and to
      deplete the electronic density of states. This finding implies that the pseudogap
      primarily arises from a change in the electronic ground state rather than from
      thermal fluctuations.

PMID- 11290207
TI  - Field-induced three- and two-dimensional freezing in a quantum spin liquid.
AB  - Field-induced commensurate transverse magnetic ordering is observed in the
      Haldane-gap compound Ni(C(5)D(14)N(2))2N(3)(PF(6)) by means of neutron
      diffraction. Depending on the direction of applied field, the high-field phase is
      shown to be either a three-dimensional ordered Neel state or a short-range
      ordered state with dominant two-dimensional spin correlations. The structure of
      the high-field phase is determined, and properties of the observed quantum phase
      transition are discussed.

PMID- 11290208
TI  - Time reparametrization group and the long time behavior in quantum glassy
      systems.
AB  - We study the long time dynamics of a quantum version of the Sherrington
      Kirkpatrick model. Time reparametrizations of the dynamical equations have a
      parallel with renormalization group transformations; in this language the long
      time behavior of this model is controlled by a reparametrization group ( R(p)G)
      fixed point of the classical dynamics. The irrelevance of quantum terms in the
      dynamical equations in the aging regime explains the classical nature of the out
      of equilibrium fluctuation-dissipation relation.

PMID- 11290209
TI  - Nature of spin excitations in two-dimensional mott insulators: undoped cuprates
      and other materials.
AB  - We investigate the excitation spectrum of a two-dimensional resonating valence
      bond (RVB) state. Treating the pi-flux phase with antiferromagnetic correlations
      as a variational ground state, we recover the long wavelength magnon as an "RVB
      exciton." However, this excitation does not exhaust the entire spectral weight
      and the high-energy spectrum is dominated by fermionic excitations. The latter
      can be observed directly by inelastic neutron scattering, and we predict their
      characteristic energy scales along different high symmetry directions in the
      magnetic Brillouin zone. We also interpret experimental results on two magnon
      Raman scattering and midinfrared absorption within this scenario.

PMID- 11290210
TI  - Mechanisms for the generation of coherent longitudinal-optical phonons in GaAs
      /AlGaAs multiple quantum wells.
AB  - We show that coherent optical phonons in GaAs multiple quantum wells are
      generated in a completely different way as compared to bulk GaAs. Unlike in bulk
      GaAs where the ultrafast screening of electric fields by photogenerated charge
      carriers is known to be dominant, three distinctive generation mechanisms
      contribute simultaneously in multiple quantum wells. The interplay between
      impulsive Raman scattering, forbidden Raman scattering, and screening of surface
      electric fields, whose relative strengths are determined by laser intensity,
      detuning from the exciton resonance, and the barrier width, generates a rich
      variety of new phenomena.

PMID- 11290211
TI  - Spin relaxation quenching in semiconductor quantum dots.
AB  - We have studied the spin dynamics in self-organized InAs/GaAs quantum dots by
      time-resolved photoluminescence performed under strictly resonant excitation. At
      low temperature, we observe strictly no decay of both the linear and the circular
      luminescence polarization. This demonstrates that the carrier spins are totally
      frozen on the exciton lifetime scale.

PMID- 11290212
TI  - Ultrafast dynamics of electron thermalization in gold.
AB  - Time-resolved surface second-harmonic generation (SHG) is used to probe electron
      relaxation processes in gold following intense laser excitation at 1.55 eV. For
      the first time, an electron temperature ( T(e)) dependent enhancement in the SHG
      signal is clearly observed at T(e) above 0.7 eV, which is shown to relate to the
      thermalization of nonequilibrium hot electrons. Therefore, the relaxation
      dynamics of the transient nonequilibrium electrons in the high T(e) regime is
      directly resolved by monitoring the time evolution of the SHG signal.

PMID- 11290213
TI  - Effect of hydrogen adsorption on the x-ray absorption spectra of small Pt
      clusters.
AB  - Hydrogen adsorption on Pt(6)H(n) clusters leads to striking changes in the Pt
      L(2,3) x-ray absorption spectra. These effects are interpreted using a self
      consistent real space Green's function approach. Calculations show that they are
      due largely to changes in the atomic background contribution to x-ray absorption
      (i.e., atomic x-ray absorption fine structure) and to reduced Pt-Pt scattering at
      the edge, while Pt-H multiple scattering is relatively weak. The origin of both
      effects is traced to the change in the local Pt potential due to Pt-H bonding.

PMID- 11290214
TI  - Wave propagation in subexcitable media with periodically modulated excitability.
AB  - Wave propagation in a photosensitive, subexcitable Belousov-Zhabotinsky medium is
      made possible by periodic modulation of a homogeneous illumination field. The
      propagation can be understood in terms of an interplay between the radial
      expansion of the wave and the motion of its free ends as the excitability varies
      periodically. This description leads to a simple kinematic analysis that provides
      insights into the initial conditions and forcing parameters giving rise to
      sustained wave propagation.

PMID- 11290215
TI  - Modeling heart rate variability in healthy humans: a turbulence analogy.
AB  - Many complex systems share similar statistical characteristics. In this Letter, a
      turbulence analogy is proposed for the long-term heart rate variability of
      healthy humans. Based on such an analogy, the equivalence of an inertial range is
      found and a cascade model, which captures the statistical properties of the heart
      rate data, is given.

PMID- 11290216
TI  - Trajectories in phase diagrams, growth processes, and computational complexity:
      how search algorithms solve the 3-satisfiability problem.
AB  - Decision and optimization problems typically fall into one of two categories for
      any particular solving algorithm. The problem is either solved quickly (easy) or
      demands an impractically long computational effort (hard). Here we show that some
      characteristic parameters of problems can be tracked during a run of the
      algorithm defining a trajectory through the parameter space. Focusing on 3
      satisfiability, a recognized representative of hard problems, we analyze
      trajectories generated by search algorithms. These trajectories can cross well
      defined phases, corresponding to domains of easy or hard instances, and allow one
      to successfully predict the times of resolution.

PMID- 11290217
TI  - Typical solution time for a vertex-covering algorithm on finite-connectivity
      random graphs.
AB  - We analytically describe the typical solution time needed by a backtracking
      algorithm to solve the vertex-cover problem on finite-connectivity random graphs.
      We find two different transitions: The first one is algorithm dependent and marks
      the dynamical transition from linear to exponential solution times. The second
      one gives the maximum computational complexity, and is found exactly at the
      threshold where the system undergoes an algorithm-independent phase transition in
      its solvability. Analytical results are corroborated by numerical simulations.

PMID- 11290218
TI  - Comment on "Creation of magnetic energy in the solar atmosphere".

PMID- 11290219
TI  - Short time scales in the Kramers problem: a stepwise growth of the escape flux.
AB  - We prove rigorously and demonstrate in simulations that, for a potential system
      staying initially at the bottom of a well, the escape flux over the barrier grows
      on times of the order of a period of eigenoscillation in a stepwise manner,
      provided that friction is small or moderate. If the initial state is not at the
      bottom of the well, then, typically, some of the steps transform into
      oscillations. The stepwise/oscillatory evolution at short times appears to be a
      generic feature of a noise-induced flux.

PMID- 11290221
TI  - Consequences of parton saturation and string percolation on the development of
      cosmic ray showers.
AB  - At high gluon or string densities, gluon saturation or the strong interaction
      among strings, either forming color ropes or giving rise to string percolation,
      induces a strong suppression in the particle multiplicities produced at high
      energy. This suppression implies important modifications on cosmic ray shower
      development. In particular, it is shown that it affects the depth of maximum, the
      elongation rate, and the behavior of the number of muons at energies about 10(17)
      -10(18) eV. The existing cosmic ray data point out in the same direction.

PMID- 11290222
TI  - Presupernova collapse models with improved weak-interaction rates.
AB  - Improved values for stellar weak-interaction rates have been recently calculated
      based upon a large shell-model diagonalization. Using these new rates (for both
      beta decay and electron capture), we have examined the presupernova evolution of
      massive stars in the range (15--40)M(o). Comparing our new models with a standard
      set of presupernova models by Woosley and Weaver, we find significantly larger
      values for the electron-to-baryon ratio at the onset of collapse and smaller iron
      core masses. These changes may have important consequences for nucleosynthesis
      and the supernova explosion mechanism.

PMID- 11290223
TI  - Brane world solution to the cosmological constant problem.
AB  - We consider a model with two parallel (positive tension) 3-branes separated by a
      distance L in five-dimensional spacetime. If the interbrane space is anti--de
      Sitter, or is not precisely anti--de Sitter but contains no event horizons, the
      effective four-dimensional cosmological constant seen by observers on one of the
      branes (chosen to be the visible brane) becomes exponentially small as L grows
      large.

PMID- 11290224
TI  - Maximal gauged supergravity in three dimensions.
AB  - We construct maximally supersymmetric gauged N = 16 supergravity in three
      dimensions, thereby obtaining an entirely new class of anti--de Sitter
      supergravities. These models apparently cannot be derived from any known higher
      dimensional theory and point to the existence of a new type of supergravity
      beyond D = 11. One of their noteworthy features is a non-Abelian generalization
      of the duality between scalar and vector fields in three dimensions. Among the
      possible gauge groups, SO(8) x SO(8) is distinguished as the maximal compact
      gauge group, but there are also more exotic possibilities such as F(4(-20)) x G2.

PMID- 11290225
TI  - Nontopological finite temperature induced fermion number.
AB  - We show that while the zero temperature induced fermion number in a chiral sigma
      model background depends only on the asymptotic values of the chiral field, at
      finite temperature the induced fermion number depends also on the detailed shape
      of the chiral background. We resum the leading low temperature terms to all
      orders in the derivative expansion, producing a simple result that can be
      interpreted physically as the different effect of the chiral background on
      virtual pairs of the Dirac sea and on the real particles of the thermal plasma.
      By contrast, for a kink background, not of sigma model form, the finite T induced
      fermion number is temperature dependent but topological.

PMID- 11290226
TI  - pp(macro)-->tt(macro)H: a discovery mode for the Higgs boson at the Fermilab
      Tevatron.
AB  - The production of a standard model Higgs boson in association with a top quark
      pair at the upcoming high luminosity run ( 15 fb(-1) integrated luminosity) of
      the Fermilab Tevatron ( square root of s = 2.0 TeV) is revisited. For Higgs
      masses below 140 GeV we demonstrate that the production cross section times
      branching ratio for H-->bb macro decays yields a significant number of events and
      that this mode is competitive with and complementary to the searches using
      pp(macro) -->WH,ZH associated production. For higher mass Higgs bosons the H-
      >W(+)W(-) decays are more difficult but have the potential to provide a few
      spectacular events.

PMID- 11290227
TI  - Direct measurement of the phi(1020) leptonic branching ratio.
AB  - The process e(+)e(-)-->mu(+)mu(-) has been studied by the SND detector at the
      VEPP-2M e(+)e(-) collider in the phi(1020)-resonance energy region. The measured
      effective phi meson leptonic branching ratio B(phi-->l(+)l(-)) identical with
      square root of B(phi-->e(+)e(-))B(phi-->mu(+)mu(-))] = (2.89 +/- 0.10 +/- 0.06) x
      10(-4) agrees well with the Particle Data Group value B(phi-->e(+)e(-)) = (2.91
      +/- 0.07) x 10(-4), confirming mu-e universality. Without additional assumption
      of mu-e universality the branching ratio B(phi-->mu(+)mu(-)) = (2.87 +/- 0.20 +/-
      0.14) x 10(-4) was obtained.

PMID- 11290231
TI  - Initial gluon multiplicity in heavy-ion collisions.
AB  - The initial gluon multiplicity per unit area per unit rapidity, dN/L2/d eta, in
      high energy nuclear collisions, is equal to f(N)(g(2)mu L) (g(2)mu)(2)/g(2), with
      mu(2) proportional to the gluon density per unit area of the colliding nuclei.
      For an SU(2) gauge theory, we compute f(N)(g(2)mu L) = 0.14 +/- 0.01 for a wide
      range in g(2)mu L. Extrapolating to SU(3), we predict dN/L2/d eta for values of
      g(2)mu L relevant to the Relativistic Heavy Ion Collider and the Large Hadron
      Collider. We compute the initial gluon transverse momentum distribution,
      dN/L2/d(2)k( perpendicular), and show it to be well behaved at low k(
      perpendicular).

PMID- 11290232
TI  - Odd-odd deformed proton emitters.
AB  - Proton decay from odd-odd deformed nuclei is a long-standing unsolved problem. We
      present for the first time an exact solution using single particle Nilsson
      resonances. The lifetime is found to depend strongly on the single particle level
      occupied by the unpaired neutron, allowing a clear assignment of its Nilsson
      level. The emitters 112Cs, 140Ho, 150Lu, and 150Lu(m) are considered. The
      agreement with the experimental data is very good with deformations 0.1<beta<0.19
      for 112Cs and -0.17<beta<-0.16 for the ground and isomeric states of 150Lu. In
      the case of 140Ho, two ranges of deformation 0.16<beta<0.28 and 0.28<beta<0.38
      according to the neutron single particle level can describe the experimental half
      life.

PMID- 11290228
TI  - The ep -->e'p eta reaction at and above the S11(1535) baryon resonance.
AB  - New cross sections for the reaction e p-->e p eta are reported for total center
      of mass energy W = 1.5--1.86 GeV and invariant momentum transfer Q2 = 0.25--1.5
      (GeV/c)(2). This large kinematic range allows extraction of important new
      information about response functions, photocouplings, and eta N coupling
      strengths of baryon resonances. Newly observed structure at W approximately 1.65
      GeV is shown to come from interference between S and P waves and can be
      interpreted with known resonances. Improved values are derived for the photon
      coupling amplitude for the S11(1535) resonance.

PMID- 11290230
TI  - Measurement of the charged pion electromagnetic form factor.
AB  - Separated longitudinal and transverse structure functions for the reaction
      1H(e,e(')pi(+))n were measured in the momentum transfer region Q2 = 0.6--1.6
      (GeV/c)(2) at a value of the invariant mass W = 1.95 GeV. New values for the pion
      charge form factor were extracted from the longitudinal cross section by using a
      recently developed Regge model. The results indicate that the pion form factor in
      this region is larger than previously assumed and is consistent with a monopole
      parametrization fitted to very low Q2 elastic data.

PMID- 11290233
TI  - Direct measurement of a pure rotation transition in H2(+).
AB  - The N = 1<--0 pure rotation transition in the nu = 19 level of the ground
      electronic state of H2(+) was observed at 14,961.7+/-1.1 MHz. Recent theory
      predicts significant electric dipole intensity in forbidden rotation and rotation
      vibration transitions involving levels near the dissociation limit; the relevant
      levels are bound by only 0.74 and 0.22 cm(-1). The transition was predicted to
      have a transition moment of 0.42 D; our measurement is consistent with this
      value.

PMID- 11290234
TI  - Insertion and abstraction pathways in the reaction O(1D2) + H2-->OH+H.
AB  - Rigorous quantum dynamical calculations have been performed on the ground 1 1A'
      and first excited 1 1A" electronic states of the title reaction, employing the
      most accurate potential energy surfaces available. Product rovibrational quantum
      state populations and rotational angular momentum alignment parameters are
      reported, and are compared with new experimental, and quasiclassical trajectory
      calculated results. The quantum calculations agree quantitatively with
      experiment, and reveal unequivocally that the 1 1A" excited state participates in
      the reaction.

PMID- 11290235
TI  - Formation of metal-encapsulating Si cage clusters.
AB  - We report the formation of a series of metal-containing hydrogenated silicon
      clusters using an ion trap. Mass analyses reveal that many types of transition
      metal ions M(+) ( M = Hf, Ta, W, Re, Ir, etc.) react with silane (SiH4) to form
      dehydrogenated MSi( +)(n) cluster ions ( n = 14, 13, 12, 11, 9, respectively) as
      an end product, indicating that the metal atom is endohedral and stabilizes the
      Si polyhedral cage. This finding is confirmed by our ab initio calculation that
      WSi12 is a W-encapsulating Si12 cage cluster, and is very stable owing to both
      the electronic and the geometrical shell closures.

PMID- 11290236
TI  - Maintenance and suppression of chaos by weak harmonic perturbations: a unified
      view.
AB  - General results concerning maintenance or enhancement of chaos are presented for
      dissipative systems subjected to two harmonic perturbations (one chaos inducing
      and the other chaos enhancing). The connection with previous results on chaos
      suppression is also discussed in a general setting. It is demonstrated that, in
      general, a second harmonic perturbation can reliably play an enhancer or
      inhibitor role by solely adjusting its initial phase. Numerical results indicate
      that general theoretical findings concerning periodic chaos-inducing
      perturbations also work for aperiodic chaos-inducing perturbations, and in arrays
      of identical chaotic coupled oscillators.

PMID- 11290237
TI  - Coherent control of quantum chaotic diffusion.
AB  - Extensive coherent control over quantum chaotic diffusion using the kicked rotor
      model is demonstrated and its origin in deviations from random matrix theory is
      identified. Further, the extent of control in the presence of external
      decoherence is established. The results are relevant to both areas of quantum
      chaos and coherent control.

PMID- 11290238
TI  - Control of chaotic Taylor-Couette flow with time-delayed feedback.
AB  - We demonstrate that unstable periodic orbits embedded in the experimental chaotic
      attractor determined by the Taylor-Couette flow can be stabilized with a time
      delay autosynchronization algorithm. The optimal parameters of the feedback and
      their dependence on the control parameter are shown as experimental results.

PMID- 11290239
TI  - Phase synchronization between several interacting processes from univariate data.
AB  - A novel approach is suggested for detecting the presence or absence of
      synchronization between two or three interacting processes with different time
      scales in univariate data. It is based on an angle-of-return-time map. A model is
      derived to describe analytically the behavior of angles for a periodic oscillator
      under weak periodic and quasiperiodic forcing. An explicit connection is
      demonstrated between the return angle and the phase of the external periodic
      forcing. The technique is tested on simulated nonstationary data and applied to
      human heart rate variability data.

PMID- 11290240
TI  - Large coherence area thin-film photonic stop-band lasers.
AB  - We demonstrate that the shift of the stop-band position with increasing oblique
      angle in periodic structures results in a wide transverse exponential field
      distribution corresponding to strong angular confinement of the radiation. The
      beam expansion follows an effective diffusive equation depending only upon the
      spectral mode width. In the presence of gain, the beam cross section is limited
      only by the size of the gain area. As an example of an active periodic photonic
      medium, we calculate and measure laser emission from a dye-doped cholesteric
      liquid crystal film.

PMID- 11290229
TI  - Inclusive jet production in pp(macro) collisions.
AB  - We report a new measurement of the pseudorapidity (eta) and transverse-energy (
      E(T)) dependence of the inclusive jet production cross section in pp(macro)
      collisions at square root of s = 1.8 TeV using 95 pb(-1) of data collected with
      the D0 detector at the Fermilab Tevatron. The differential cross section
      d(2)sigma/(dE(T)d eta) is presented up to eta = 3, significantly extending
      previous measurements. The results are in good overall agreement with next-to
      leading order predictions from QCD and indicate a preference for certain parton
      distribution functions.

PMID- 11290241
TI  - Creep motion in a granular pile exhibiting steady surface flow.
AB  - We investigate experimentally granular piles exhibiting steady surface flow.
      Below the surface flow, it has been believed that a "frozen" bulk region exists,
      but our results show no such frozen bulk. We report here that even the particles
      in layers deep in the bulk exhibit very slow flow and that such motion can be
      detected at an arbitrary depth. The mean velocity of the creep motion decays
      exponentially with depth, and the characteristic decay length is approximately
      equal to the particle size and is independent of the flow rate. It is expected
      that the creep motion we have seen is observable in all sheared granular systems.

PMID- 11290243
TI  - Energy-gain measurements from a microwave inverse free-electron-laser
      accelerator.
AB  - Experiments are reported on inverse free-electron-laser acceleration, including
      for the first time observations of the energy change as a function of relative
      injection phase of the electron bunches. The microwave accelerating structure
      consists of a uniform circular waveguide with a helical wiggler and an axial
      magnetic field. Acceleration of the entire beam by 6% is seen for 6 MeV electron
      bunches at optimum relative phase. Experimental results compare favorably, for
      accelerating phases, with predictions of a three-dimensional simulation that
      includes large-orbit effects.

PMID- 11290242
TI  - Statistical equilibrium solutions of the shallow water equations.
AB  - A statistical method for calculating equilibrium solutions of the shallow water
      equations, a model of essentially 2D fluid flow with a free surface, is
      described. The model contains a competing acoustic turbulent direct energy
      cascade, and a 2D turbulent inverse energy cascade. It is shown, nonetheless
      that, just as in the corresponding theory of the inviscid Euler equation, the
      infinite number of conserved quantities constrains the flow sufficiently to
      produce nontrivial large-scale vortex structures which are solutions to a set of
      explicitly derived coupled nonlinear partial differential equations.

PMID- 11290244
TI  - Effect of plasma scale length on multi-MeV proton production by intense laser
      pulses.
AB  - The influence of the plasma density scale length on the production of MeV protons
      from thin foil targets irradiated at I lambda(2) = 5 x 10(19) W cm(-2) has been
      studied. With an unperturbed foil, protons with energy >20 MeV were formed in an
      exponential energy spectrum with a temperature of 2.5+/-0.3 MeV. When a plasma
      with a scale length of 100 microm was preformed on the back of the foil, the
      maximum proton energy was reduced to <5 MeV and the beam was essentially
      destroyed. The experimental results are consistent with an electrostatic
      accelerating mechanism that requires an ultrashort scale length at the back of
      the target.

PMID- 11290245
TI  - Structural transformation in the formation of H-induced (111) platelets in Si.
AB  - On the basis of first-principles calculations, we present a structural model for
      the formation of H-induced (111) platelets in Si, which involves a structural
      transformation from a double-layer-H2(*) configuration of H2(*) aggregates into
      an H-saturated internal (111) surface structure. This reaction process preferably
      occurs at high H plasma treatment temperatures and subsequently generates H2
      molecules in the platelet voids, consistent with experiments. Our model also
      reveals the important features observed in (111) platelets, such as high
      resolution transmission electron microscopy images, step structures, lattice
      dilation lengths, and H vibrational frequencies.

PMID- 11290246
TI  - Mechanism of interconversion among radiation-induced defects in amorphous silicon
      dioxide.
AB  - We here present a series of ab initio quantum-chemical calculations on clusters
      of atoms modeling several oxygen-deficiency-related defects in amorphous silica
      and illustrate how these defect centers will change their atomic configurations
      upon photoionization. We first give theoretical evidence that structural
      conversion from a neutral oxygen monovacancy to a divalent Si defect is possible,
      explaining the observed photoluminescence properties associated with these
      defects.

PMID- 11290247
TI  - Dynamics of some constrained lattices.
AB  - We consider the dynamics of lattices which have constrained constitutive units
      flexible in only their mutual orientations. A continuum description is derived
      through which it is shown that the models have zero shear velocity, free-particle
      like internal rotational modes and volume decreasing linearly with temperature.
      The relevance of models to a range of problems is pointed out.

PMID- 11290248
TI  - Renormalization of pinned elastic systems: how does it work beyond one loop?
AB  - We study the field theories for pinned elastic systems at equilibrium and at
      depinning. Their beta functions differ to two loops by novel "anomalous" terms.
      At equilibrium we find a roughness zeta = 0.208 298 04 epsilon + 0.006 858
      epsilon(2) (random bond), zeta = epsilon/3 (random field). At depinning we prove
      two-loop renormalizability and that random field attracts shorter range disorder.
      We find zeta = epsilon/3(1 + 0.143 31 epsilon), epsilon = 4 - d, in violation of
      the conjecture zeta = epsilon/3, solving the discrepancy with simulations. For
      long range elasticity zeta = epsilon/3(1 + 0.397 35 epsilon), epsilon = 2 - d,
      much closer to the experimental value (approximately 0.5 both for liquid helium
      contact line depinning and slow crack fronts) than the standard prediction 1/3.

PMID- 11290249
TI  - Nitrogen solubility and induced defect complexes in epitaxial GaAs:N.
AB  - Thermodynamic calculation suggests that the formation of bulk GaN pins N chemical
      potential mu(N)< or =mu(max)(N), resulting in low equilibrium N solubility [N] in
      bulk GaAs:N. In epitaxial growth, however, a fully relaxed GaN phase cannot form
      prior to the spontaneous formation of a N-rich layer on the surface. First
      principles total-energy calculations show that in the epitaxial regime one can
      increase mu(max)(N) considerably from equilibrium mu(max)(N) without triggering
      the spontaneous formation of such a N-rich layer. This enhances [N] by 8 orders
      of magnitude to about 4% at T = 650 degrees C in agreement with experiments. The
      dominant defects at high N concentration are qualitatively different from those
      at low [N].

PMID- 11290250
TI  - Mechanism for the enhanced diffusion of charged oxygen ions in SiO2.
AB  - Based on real-space multigrid electronic structure calculations, we find that a
      double Si-O-Si bridge structure is the lowest energy configuration of
      interstitial oxygen ions (O(-) and O(2-)) in SiO2, where two additional Si-O
      bonds are formed with almost no interaction between the interstitial and host O
      atoms, while the peroxy linkage is the most stable structure for neutral
      interstitial O. We propose a diffusion mechanism of interstitial O ions generated
      from molecular O2 under UV radiation, and find extremely low energy barriers of
      0.11--0.27 eV for migration in the form of the double-bridge structure, in good
      agreement with enhanced oxidation experiments.

PMID- 11290251
TI  - Power laws and crossovers in off-critical surface-directed spinodal
      decomposition.
AB  - We study the dynamics of phase separation in binary mixtures near a surface with
      a preferential attraction for one of the components of the mixture. We obtain
      detailed numerical results for a range of mixture compositions. In the case where
      the minority component is attracted to the surface, wetting layer growth is
      characterized by a crossover from a surface-potential-dependent growth law to a
      universal law. We formulate a simple phenomenological model to explain our
      numerical results.

PMID- 11290252
TI  - Surface structure of SrTiO3(100)-(square root of 5 x square root of 5) - R26.6
      degrees.
AB  - Atomic and electronic structures of the SrTiO3(100)-(square root of 5 x square
      root of 5) - R26.6 degrees surface are studied by using scanning tunneling
      microscopy (STM) and noncontact atomic force microscopy (NC-AFM). Instead of the
      well established oxygen vacancy model, it is found that a structural model,
      consisting of an ordered Sr adatom at the oxygen fourfold site of a TiO2
      terminated layer, can explain the experimental results very well. We
      theoretically simulate the model cluster with the first-principles total-energy
      calculation. Calculated density of states and images for STM and NC-AFM are in
      good agreement with the experimental results.

PMID- 11290253
TI  - Dissipative quantum dynamics in 2D: anisotropic dissipation and selective bond
      breaking in surface photochemistry.
AB  - The dissipative quantum dynamics of a model system, O2 at a Pt(111) surface, has
      been solved in two dimensions using a stochastic wave packet approach and
      parallel-computing techniques. It is found that, upon excitation, the dissipation
      anisotropy creates nonequilibrium and anisotropic energy storage between
      different reaction channels. The latter determines decisively the short-time
      reaction dynamics and, in particular, the branching ratio between desorption and
      dissociation, in agreement with recent experimental findings.

PMID- 11290255
TI  - Ab initio absorption spectra and optical gaps in nanocrystalline silicon.
AB  - The optical absorption spectra of Si(n)H(m) nanoclusters up to approximately 250
      atoms are computed using a linear response theory within the time-dependent local
      density approximation (TDLDA). The TDLDA formalism allows the electronic
      screening and correlation effects, which determine exciton binding energies, to
      be naturally incorporated within an ab initio framework. We find the calculated
      excitation energies and optical absorption gaps to be in good agreement with
      experiment in the limit of both small and large clusters. The TDLDA absorption
      spectra exhibit substantial blueshifts with respect to the spectra obtained
      within the time-independent local density approximation.

PMID- 11290254
TI  - Direct visualization of defect density waves in 2D.
AB  - A scanning tunneling microscopy investigation of the 1/3 of a monolayer alpha
      phase of Sn on Si(111) reveals a new low temperature phase, which is electronic
      and not structural. This phase consists of a one-dimensional incommensurate
      electronic wave that coincides with a periodic modulation of the population of
      the substitutional Si defects, i.e., a defect density wave.

PMID- 11290256
TI  - Instanton approach to the Langevin motion of a particle in a random potential.
AB  - We develop an instanton approach to the nonequilibrium dynamics in one
      dimensional random environments. The long time behavior is controlled by rare
      fluctuations of the disorder potential and, accordingly, by the tail of the
      distribution function for the time a particle needs to propagate along the system
      (the delay time). The proposed method allows us to find the tail of the delay
      time distribution function and delay time moments, providing thus an exact
      description of the long time dynamics. We analyze arbitrary environments covering
      different types of glassy dynamics: dynamics in a short-range random field,
      creep, and Sinai's motion.

PMID- 11290258
TI  - Interlayer tunneling in double-layer quantum hall pseudoferromagnets.
AB  - We show that the interlayer tunneling I-V in double-layer quantum Hall states
      displays a rich behavior which depends on the relative magnitude of sample size,
      voltage length scale, current screening, disorder, and thermal lengths. For weak
      tunneling, we predict a negative differential conductance of a power-law shape
      crossing over to a sharp zero-bias peak. An in-plane magnetic field splits this
      zero-bias peak, leading instead to a "derivative" feature at V(B)(B(parallel)) =
      2 pi Planck's over 2 pi upsilon B(parallel)d/e phi(0), which gives a direct
      measurement of the dispersion of the Goldstone mode corresponding to the
      spontaneous symmetry breaking of the double-layer Hall state.

PMID- 11290257
TI  - Geometry-dependent dephasing in small metallic wires.
AB  - Temperature dependent weak localization is measured in metallic nanowires in a
      previously unexplored size regime down to width w = 5 nm. The dephasing time,
      tau(phi), shows a low temperature T dependence close to quasi-1D theoretical
      expectations (tau(phi) approximately T(-2/3)) in the narrowest wires, but
      exhibits a relative saturation as T-->0 for wide samples of the same material, as
      observed previously. As only sample geometry is varied to exhibit both
      suppression and divergence of tau(phi), this finding provides a new constraint on
      models of dephasing phenomena.

PMID- 11290259
TI  - Theory of interlayer tunneling in bilayer quantum Hall ferromagnets.
AB  - Spielman et al. [Phys. Rev. Lett. 84, 5808 (2000] recently observed a large and
      sharp Josephson-like zero-bias peak in the tunnel conductance of a bilayer system
      in a quantum Hall ferromagnet state. We argue that disorder-induced topological
      defects in the pseudospin order parameter limit the peak size and destroy the
      predicted Josephson effect. We predict that the peak would be split and shifted
      by an in-plane magnetic field in a way that maps the dispersion relation of the
      ferromagnet's Goldstone mode. We also predict resonant structures in the dc I-V
      characteristic under bias by an ac electric field.

PMID- 11290260
TI  - Josephson effect without superconductivity: realization in quantum Hall bilayers.
AB  - We show that a quantum Hall bilayer with the total filling nu = 1 should exhibit
      a dynamical regime similar to the flux flow in large Josephson junctions. This
      analogy may explain a conspicuous peak in the interlayer tunneling conductance
      [Phys. Rev. Lett. 84, 5808 (2000)]. The flux flow is likely to be
      spatiotemporally chaotic at low-bias voltage, which will manifest itself through
      broadband noise. The peak position can be controlled by an in-plane magnetic
      field.

PMID- 11290261
TI  - Modification of the intersubband excitation spectrum in a two-dimensional
      electron system under a perpendicular magnetic field.
AB  - Under an external magnetic field, new branches of spin- and charge-density waves
      have been studied in a quasi-two-dimensional electron system whose ground state
      has more than one Landau level occupied by electrons. These collective
      excitations can be treated as manifestations of the multicomponent nature of the
      electron system in magnetic field, whereas the occupied Landau levels should be
      associated with degrees of freedom.

PMID- 11290262
TI  - Coulomb drag in coherent mesoscopic systems.
AB  - We present a theory for Coulomb drag between two mesoscopic systems. Our
      formalism expresses the drag in terms of scattering matrices and wave functions,
      and its range of validity covers both ballistic and disordered systems. The
      consequences can be worked out either by analytic means, such as the random
      matrix theory, or by numerical simulations. We show that Coulomb drag is
      sensitive to localized states, which usual transport measurements do not probe.
      For chaotic 2D systems we find a vanishing average drag, with a nonzero variance.
      Disordered 1D wires show a finite drag, with a large variance, giving rise to a
      possible sign change of the induced current.

PMID- 11290263
TI  - Electronic correlation effects and the Coulomb gap at finite temperature.
AB  - We have investigated the effect of the long-range Coulomb interaction on the one
      particle excitation spectrum of n-type germanium, using tunneling spectroscopy on
      mechanically controllable break junctions. At low temperatures, the tunnel
      conductance shows a minimum at zero bias voltage due to the Coulomb gap. Above 1
      K, the gap is filled by thermal excitations. This behavior is reflected in the
      variable-range hopping resistivity measured on the same samples: up to a few
      degrees Kelvin the Efros-Shklovskii lnR infinity T(-1/2) law is obeyed, whereas
      at higher temperatures deviations from this law occur. The type of crossover
      differs from that considered previously in the literature.

PMID- 11290264
TI  - Strong correlation to weak correlation phase transition in bilayer quantum Hall
      systems.
AB  - At small layer separations, the ground state of a nu = 1 bilayer quantum Hall
      system exhibits spontaneous interlayer phase coherence. The evolution of this
      state with increasing layer separation d has been a matter of controversy. We
      report on small system exact diagonalization calculations which suggest that a
      single-phase transition, likely of first order, separates incompressible states
      with strong interlayer correlations from compressible states with weak interlayer
      correlations. We find a dependence of the phase boundary on d and interlayer
      tunneling amplitude that is in very good agreement with recent experiments.

PMID- 11290265
TI  - Bilayer coherent and quantum Hall phases: duality and quantum disorder.
AB  - We consider a fully spin-polarized quantum Hall system with no interlayer
      tunneling at total filling factor nu = 1/k (where k is an odd integer) using the
      Chern-Simons-Ginzburg-Landau theory. Exploiting particle-vortex duality and the
      concept of quantum disordering, we find a large number of possible compressible
      and incompressible ground states, some of which may have relevance to recent
      experiments of Spielman et al. [Phys. Rev. Lett. 84, 5808 (2000)]. We find
      interlayer coherent compressible states without Hall quantization and interlayer
      incoherent incompressible states with Hall quantization in addition to the usual
      (k,k,k) Halperin states, which are both interlayer coherent and incompressible.

PMID- 11290266
TI  - Quantum interference in artificial band structures.
AB  - Magnetotransport experiments on two-dimensional electron systems with an
      atomically precise, one-dimensional potential modulation reveal striking quantum
      interference oscillations. Within a semiclassical framework, they are recognized
      either as self-interference along closed orbits, many of them rendered possible
      by magnetic breakdown between Fermi contour segments of the artificial band
      structure, or as interference-enhanced backscattering. The known commensurability
      oscillations appear as a special case of the latter mechanism.

PMID- 11290267
TI  - Predicted superconductive properties of lithium under pressure.
AB  - A superconducting state of lithium has not been found at ambient pressure, but
      the present theoretical work shows that high values of the critical temperature,
      T(c), may be expected for some high-pressure phases. Ab initio electronic
      structure calculations are used to calculate the electron-phonon coupling in a
      "rigid-muffin-tin approximation," and estimates using McMillan's formula suggest
      that under increasing pressure T(c) in fcc-Li may reach 50--70 K before
      transitions occur to the rhombohedral (hR1-Li) and subsequently to the cI16-Li
      phase near 40 GPa. In cI16-Li T(c) may reach a maximum in the range 60--80 K.

PMID- 11290268
TI  - Antiferromagnetic spin ladders effectively coupled by one-dimensional electron
      liquids.
AB  - We study a model of the stripe state in strongly correlated systems consisting of
      an array of antiferromagnetic spin ladders, each with n(leg) legs, coupled to
      each other through the spin-exchange interaction to charged stripes in between
      each pair of ladders. The charged stripes are assumed to be Luttinger liquids in
      a spin-gap regime. An effective interaction for a pair of neighboring ladders is
      calculated by integrating out the gapped spin degrees of freedom in the charged
      stripes. The low energy effective theory of each ladder is a nonlinear sigma
      model with additional cross couplings of neighboring ladders, which favor either
      in-phase or antiphase short-range spin orderings depending on the physical
      parameters of the charged stripe.

PMID- 11290269
TI  - Quantum superconductor-metal transition in a proximity array.
AB  - A theory of the zero-temperature superconductor-metal transition is developed for
      an array of superconductive islands (of size d) coupled via a disordered two
      dimensional conductor with the dimensionless conductance g = Planck's over 2
      pi/e(2)R(square)>>1. At T = 0 the macroscopically superconductive state of the
      array with lattice spacing b>>d is destroyed at g<g(c) approximately
      0.1ln(2)(b/d). At high temperatures the normal-state resistance between
      neighboring islands at b = b(c) is much smaller than R(Q) = h/4e(2).

PMID- 11290270
TI  - Strong vortex liquid correlation from multiterminal measurements on untwinned
      YBa2Cu3O(7-delta) single crystals.
AB  - Multiterminal transport measurements indicating a strongly correlated vortex
      liquid above the first order melting transition in untwinned YBa2Cu3O(7--delta)
      single crystals are presented. The correlation is found to be surprisingly stable
      for different weak variations of point disorder. We investigate the differences
      between intervortex and intravortex correlations in different contact geometries.
      The results are in agreement with the local conductivity model, with zero
      resistivity along straight vortex line segments.

PMID- 11290271
TI  - Boron isotope effect in superconducting MgB2.
AB  - We report the preparation method of and boron isotope effect for MgB2, a new
      binary intermetallic superconductor with a remarkably high superconducting
      transition temperature T(c)(10B) = 40.2 K. Measurements of both temperature
      dependent magnetization and specific heat reveal a 1.0 K shift in T(c) between
      Mg11B2 and Mg10B2. Whereas such a high transition temperature might imply exotic
      coupling mechanisms, the boron isotope effect in MgB2 is consistent with the
      material being a phonon-mediated BCS superconductor.

PMID- 11290272
TI  - Resonating valence bond phase in the triangular lattice quantum dimer model.
AB  - We study the quantum dimer model on the triangular lattice, which is expected to
      describe the singlet dynamics of frustrated Heisenberg models in phases where
      valence bond configurations dominate their physics. We find, in contrast to the
      square lattice, that there is a truly short ranged resonating valence bond phase
      with no gapless excitations and with deconfined, gapped, spinons for a finite
      range of parameters. We also establish the presence of crystalline dimer phases.

PMID- 11290273
TI  - Formation of a magnetic soliton lattice in copper metaborate.
AB  - The magnetic ground state of CuB2O4 is incommensurate at T = 1.8 K and undergoes
      a continuous phase transition to a noncollinear commensurate antiferromagnetic
      state at T(small star), filled approximately 10 K. Close to T(small star), filled
      higher-order magnetic satellites are observed. Coexistence of long- and short
      range magnetic order is observed in both magnetic phases. This suggests that the
      association of the Dzyaloshinskii-Moriya interaction and anisotropy leads to the
      formation of a magnetic soliton lattice.

PMID- 11290274
TI  - Implementation of the quantum Fourier transform.
AB  - A quantum Fourier transform (QFT) has been implemented on a three qubit nuclear
      magnetic resonance (NMR) quantum computer to extract the periodicity of an input
      state. Implementation of a QFT provides a first step towards the realization of
      Shor's factoring and other quantum algorithms. The experimental implementation of
      the QFT on a periodic state is presented along with a quantitative measure of its
      efficiency measured through state tomography. Experimentally realizing the QFT is
      a clear demonstration of the ability of NMR to control quantum systems.

PMID- 11290275
TI  - Communicating with optical hyperchaos: information encryption and decryption in
      delayed nonlinear feedback systems.
AB  - Recent theoretical studies and experimental demonstrations have shown the
      possibility of using chaos for the encryption of message signals in communication
      systems. Chaos is generated by systems with delayed nonlinear feedback, which
      feature hyperchaotic (i.e., of high dimensionality) dynamics. The different ways
      for the injection of the information in the emitter and the process of the
      synchronization of the receiver are considered. The analysis of all the
      possibilities can be used to choose the correct topology of communication systems
      and, more generally, to explain the behavior of any chaotic systems ruled by
      nonlinear difference-differential equations.

PMID- 11290276
TI  - Perturbative approach to the Bak-Sneppen model.
AB  - We study the Bak-Sneppen model in the probabilistic framework of the run time
      statistics (RTS). This model has attracted a large interest for its simplicity
      being a prototype for the whole class of models showing self-organized
      criticality. The dynamics is characterized by a self-organization of almost all
      the species fitnesses above a nontrivial threshold value, and by a lack of
      spatial and temporal characteristic scales. This results in avalanches of
      activity power law distributed. In this Letter we use the RTS approach to compute
      the value of x(c), the value of the avalanche exponent tau, and the asymptotic
      distribution of minimal fitnesses.

PMID- 11290278
TI  - Interface dynamics of lipid membrane spreading on solid surfaces.
AB  - As a model system for two-dimensional interface dynamics, we study the wetting
      front of a lipid membrane moving over a solid substrate that is structured with
      regularly spaced pinning centers. By analyzing the contour of the front, we
      derive the normal growth rate and the relaxation coefficient. Both exhibit a
      1/t(1/2) time dependence. Moreover, the friction coefficient and the line tension
      can be determined. Randomly distributed pinning centers cause a fractal contour
      line, whereas on surfaces that are artificially roughened, self-affine contour
      lines are observed. The latter exhibit an anomalous roughness exponent of zeta =
      0.81+/-0.05.

PMID- 11290277
TI  - Magnitude and sign correlations in heartbeat fluctuations.
AB  - We propose an approach for analyzing signals with long-range correlations by
      decomposing the signal increment series into magnitude and sign series and
      analyzing their scaling properties. We show that signals with identical long
      range correlations can exhibit different time organization for the magnitude and
      sign. We find that the magnitude series relates to the nonlinear properties of
      the original time series, while the sign series relates to the linear properties.
      We apply our approach to the heartbeat interval series and find that the
      magnitude series is long-range correlated, while the sign series is
      anticorrelated and that both magnitude and sign series may have clinical
      applications.

PMID- 11290279
TI  - Comment on "Two-photon Franson-type experiment and local realism".

PMID- 11290281
TI  - A convergence analysis of unconstrained and bound constrained evolutionary
      pattern search.
AB  - We present and analyze a class of evolutionary algorithms for unconstrained and
      bound constrained optimization on R(n): evolutionary pattern search algorithms
      (EPSAs). EPSAs adaptively modify the step size of the mutation operator in
      response to the success of previous optimization steps. The design of EPSAs is
      inspired by recent analyses of pattern search methods. We show that EPSAs can be
      cast as stochastic pattern search methods, and we use this observation to prove
      that EPSAs have a probabilistic, weak stationary point convergence theory. This
      convergence theory is distinguished by the fact that the analysis does not
      approximate the stochastic process of EPSAs, and hence it exactly characterizes
      their convergence properties.

PMID- 11290283
TI  - A normed space of genetic operators with applications to scalability issues.
AB  - We define an abstract normed vector space where the genetic operators are
      elements. This is used to define the disturbance of the generational operator G
      as the distance between the crossover and mutation operator (combined) and the
      identity. This quantity appears in a bound on the variance of fixed-point
      populations, and in a bound on the force //v - G(v)// that applies to the optimal
      population v. When analyzed for the case of fixed-length binary strings, a
      connection is shown between these measures and the size of the search space.
      Guides for parameter settings are given, if population convergence is required as
      the string length tends to infinity.

PMID- 11290284
TI  - Gene expression and fast construction of distributed evolutionary representation.
AB  - The gene expression process in nature produces different proteins in different
      cells from different portions of the DNA. Since proteins control almost every
      important activity in a living organism, at an abstract level, gene expression
      can be viewed as a process that evaluates the merit or "fitness" of the DNA. This
      distributed evaluation of the DNA would not be possible without a decomposed
      representation of the fitness function defined over the DNAs. This paper argues
      that, unless the living body was provided with such a representation, we have
      every reason to believe that it must have an efficient mechanism to construct
      this distributed representation. This paper demonstrates polynomial-time
      computability of such a representation by proposing a class of efficient
      algorithms. The main contribution of this paper is two-fold. On the algorithmic
      side, it offers a way to scale up evolutionary search by detecting the underlying
      structure of the search space. On the biological side, it proves that the
      distributed representation of the evolutionary fitness function in gene
      expression can be computed in polynomial-time. It advances our understanding
      about the representation construction in gene expression from the perspective of
      computing. It also presents experimental results supporting the theoretical
      performance of the proposed algorithms.

PMID- 11290285
TI  - A genetic engineering approach to genetic algorithms.
AB  - We present an extension to the standard genetic algorithm (GA), which is based on
      concepts of genetic engineering. The motivation is to discover useful and harmful
      genetic materials and then execute an evolutionary process in such a way that the
      population becomes increasingly composed of useful genetic material and
      increasingly free of the harmful genetic material. Compared to the standard GA,
      it provides some computational advantages as well as a tool for automatic
      generation of hierarchical genetic representations specifically tailored to suit
      certain classes of problems.

PMID- 11290286
TI  - Where genetic algorithms excel.
AB  - We analyze the performance of a genetic algorithm (GA) we call Culling, and a
      variety of other algorithms, on a problem we refer to as the Additive Search
      Problem (ASP). We show that the problem of learning the Ising perceptron is
      reducible to a noisy version of ASP. Noisy ASP is the first problem we are aware
      of where a genetic-type algorithm bests all known competitors. We generalize ASP
      to k-ASP to study whether GAs will achieve "implicit parallelism" in a problem
      with many more schemata. GAs fail to achieve this implicit parallelism, but we
      describe an algorithm we call Explicitly Parallel Search that succeeds. We also
      compute the optimal culling point for selective breeding, which turns out to be
      independent of the fitness function or the population distribution. We also
      analyze a mean field theoretic algorithm performing similarly to Culling on many
      problems. These results provide insight into when and how GAs can beat competing
      methods.

PMID- 11290288
TI  - Vitronectin regulates Sonic hedgehog activity during cerebellum development
      through CREB phosphorylation.
AB  - During development of the cerebellum, Sonic hedgehog (SHH) is expressed in
      migrating and settled Purkinje neurons and is directly responsible for
      proliferation of granule cell precursors in the external germinal layer. We have
      previously demonstrated that SHH interacts with vitronectin in the
      differentiation of spinal motor neurons. Here, we analysed whether similar
      interactions between SHH and extracellular matrix glycoproteins regulate
      subsequent steps of granule cell development. Laminins and their integrin
      receptor subunit alpha6 accumulate in the outer most external germinal layer
      where proliferation of granule cell precursors is maximal. Consistent with this
      expression pattern, laminin significantly increases SHH-induced proliferation in
      primary cultures of cerebellar granule cells. Vitronectin and its integrin
      receptor subunits alpha(v) are expressed in the inner part of the external
      germinal layer where granule cell precursors exit the cell cycle and commence
      differentiation. In cultures, vitronectin is able to overcome SHH-induced
      proliferation, thus allowing granule cell differentiation. Our studies indicate
      that the pathway in granule cell precursors responsible for the conversion of a
      proliferative SHH-mediated response to a differentiation signal depends on CREB.
      Vitronectin stimulates phosphorylation of cyclic-AMP responsive element-binding
      protein (CREB), and over-expression of CREB is sufficient to induce granule cell
      differentiation in the presence of SHH. Taken together, these data suggest that
      granule neuron differentiation is regulated by the vitronectin-induced
      phosphorylation of CREB, a critical event that terminates SHH-mediated
      proliferation and permits the differentiation program to proceed in these cells.

PMID- 11290289
TI  - The C. elegans homolog of the murine cystic kidney disease gene Tg737 functions
      in a ciliogenic pathway and is disrupted in osm-5 mutant worms.
AB  - Cilia and flagella are important organelles involved in diverse functions such as
      fluid and cell movement, sensory perception and embryonic patterning. They are
      devoid of protein synthesis, thus their formation and maintenance requires the
      movement of protein complexes from the cytoplasm into the cilium and flagellum
      axoneme by intraflagellar transport (IFT), a conserved process common to all
      ciliated or flagellated eukaryotic cells. We report that mutations in the
      Caenorhabditis elegans gene Y41g9a.1 are responsible for the ciliary defects in
      osm-5 mutant worms. This was confirmed by transgenic rescue of osm-5(p813)
      mutants using the wild-type Y41g9a.1 gene. osm-5 encodes a tetratricopeptide
      repeat (TPR)-containing protein that is the homolog of murine polaris (Tg737), a
      protein associated with cystic kidney disease and left-right axis patterning
      defects in the mouse. osm-5 is expressed in ciliated sensory neurons in C.
      elegans and its expression is regulated by DAF-19, an RFX-type transcription
      factor that governs the expression of other genes involved in cilia formation in
      the worm. Similar to murine polaris, the OSM-5 protein was found to concentrate
      at the cilium base and within the cilium axoneme as shown by an OSM-5::GFP
      translational fusion and immunofluorescence. Furthermore, time-lapse imaging of
      OSM-5::GFP fusion protein shows fluorescent particle migration within the cilia.
      Overall, the data support a crucial role for osm-5 in a conserved ciliogenic
      pathway, most likely as a component of the IFT process.
      http://www.biologists.com/Development/movies/dev3342.html

PMID- 11290290
TI  - The HCL gene of Medicago truncatula controls Rhizobium-induced root hair curling.
AB  - The symbiotic infection of the model legume Medicago truncatula by Sinorhizobium
      meliloti involves marked root hair curling, a stage where entrapment of the
      microsymbiont occurs in a chamber from which infection thread formation is
      initiated within the root hair. We have genetically dissected these early
      symbiotic interactions using both plant and rhizobial mutants and have identified
      a M. truncatula gene, HCL, which controls root hair curling. S. meliloti Nod
      factors, which are required for the infection process, induced wild-type
      epidermal nodulin gene expression and root hair deformation in hcl mutants, while
      Nod factor induction of cortical cell division foci was reduced compared to wild
      type plants. Studies of the position of nuclei and of the microtubule
      cytoskeleton network of hcl mutants revealed that root hair, as well as cortical
      cells, were activated in response to S. meliloti. However, the asymmetric
      microtubule network that is typical of curled root hairs, did not form in the
      mutants, and activated cortical cells did not become polarised and did not
      exhibit the microtubular cytoplasmic bridges characteristic of the pre-infection
      threads induced by rhizobia in M. truncatula. These data suggest that hcl
      mutations alter the formation of signalling centres that normally provide
      positional information for the reorganisation of the microtubular cytoskeleton in
      epidermal and cortical cells.

PMID- 11290291
TI  - The role of Wingless signaling in establishing the anteroposterior and
      dorsoventral axes of the eye disc.
AB  - The posteriorly expressed signaling molecules Hedgehog and Decapentaplegic drive
      photoreceptor differentiation in the Drosophila eye disc, while at the anterior
      lateral margins Wingless expression blocks ectopic differentiation. We show here
      that mutations in axin prevent photoreceptor differentiation and lead to tissue
      overgrowth and that both these effects are due to ectopic activation of the
      Wingless pathway. In addition, ectopic Wingless signaling causes posterior cells
      to take on an anterior identity, reorienting the direction of morphogenetic
      furrow progression in neighboring wild-type cells. We also show that signaling by
      Decapentaplegic and Hedgehog normally blocks the posterior expression of anterior
      markers such as Eyeless. Wingless signaling is not required to maintain anterior
      Eyeless expression and in combination with Decapentaplegic signaling can promote
      its downregulation, suggesting that additional molecules contribute to anterior
      identity. Along the dorsoventral axis of the eye disc, Wingless signaling is
      sufficient to promote dorsal expression of the Iroquois gene mirror, even in the
      absence of the upstream factor pannier. However, Wingless signaling does not lead
      to ventral mirror expression, implying the existence of ventral repressors.

PMID- 11290292
TI  - A novel role for VEGF in endocardial cushion formation and its potential
      contribution to congenital heart defects.
AB  - Normal cardiovascular development is exquisitely dependent on the correct dosage
      of the angiogenic growth factor and vascular morphogen vascular endothelial
      growth factor (VEGF). However, cardiac expression of VEGF is also robustly
      augmented during hypoxic insults, potentially mediating the well-established
      teratogenic effects of hypoxia on heart development. We report that during normal
      heart morphogenesis VEGF is specifically upregulated in the atrioventricular (AV)
      field of the heart tube soon after the onset of endocardial cushion formation
      (i.e. the endocardium-derived structures that build the heart septa and valves).
      To model hypoxia-dependent induction of VEGF in vivo, we conditionally induced
      VEGF expression in the myocardium using a tetracycline-regulated transgenic
      system. Premature induction of myocardial VEGF in E9.5 embryos to levels
      comparable with those induced by hypoxia prevented formation of endocardial
      cushions. When added to explanted embryonic AV tissue, VEGF fully inhibited
      endocardial-to-mesenchymal transformation. Transformation was also abrogated in
      AV explants subjected to experimental hypoxia but fully restored in the presence
      of an inhibitory soluble VEGF receptor 1 chimeric protein. Together, these
      results suggest a novel developmental role for VEGF as a negative regulator of
      endocardial-to-mesenchymal transformation that underlies the formation of
      endocardial cushions. Moreover, ischemia-induced VEGF may be the molecular link
      between hypoxia and congenital defects in heart septation.

PMID- 11290294
TI  - Overexpression of Hoxc13 in differentiating keratinocytes results in
      downregulation of a novel hair keratin gene cluster and alopecia.
AB  - Studying the roles of Hox genes in normal and pathological development of skin
      and hair requires identification of downstream target genes in genetically
      defined animal models. We show that transgenic mice overexpressing Hoxc13 in
      differentiating keratinocytes of hair follicles develop alopecia, accompanied by
      a progressive pathological skin condition that resembles ichthyosis. Large-scale
      analysis of differential gene expression in postnatal skin of these mice
      identified 16 previously unknown and 13 known genes as presumptive Hoxc13
      targets. The majority of these targets are downregulated and belong to a subgroup
      of genes that encode hair-specific keratin-associated proteins (KAPs). Genomic
      mapping using a mouse hamster radiation hybrid panel showed these genes to reside
      in a novel KAP gene cluster on mouse chromosome 16 in a region of conserved
      linkage with human chromosome 21q22.11. Furthermore, data obtained by Hoxc13/lacZ
      reporter gene analysis in mice that overexpress Hoxc13 suggest negative
      autoregulatory feedback control of Hoxc13 expression levels, thus providing an
      entry point for elucidating currently unknown mechanisms that are required for
      regulating quantitative levels of Hox gene expression. Combined, these results
      provide a framework for understanding molecular mechanisms of Hoxc13 function in
      hair growth and development.

PMID- 11290293
TI  - Developmentally distinct MYB genes encode functionally equivalent proteins in
      Arabidopsis.
AB  - The duplication and divergence of developmental control genes is thought to have
      driven morphological diversification during the evolution of multicellular
      organisms. To examine the molecular basis of this process, we analyzed the
      functional relationship between two paralogous MYB transcription factor genes,
      WEREWOLF (WER) and GLABROUS1 (GL1), in Arabidopsis. The WER and GL1 genes specify
      distinct cell types and exhibit non-overlapping expression patterns during
      Arabidopsis development. Nevertheless, reciprocal complementation experiments
      with a series of gene fusions showed that WER and GL1 encode functionally
      equivalent proteins, and their unique roles in plant development are entirely due
      to differences in their cis-regulatory sequences. Similar experiments with a
      distantly related MYB gene (MYB2) showed that its product cannot functionally
      substitute for WER or GL1. Furthermore, an analysis of the WER and GL1 proteins
      shows that conserved sequences correspond to specific functional domains. These
      results provide new insights into the evolution of the MYB gene family in
      Arabidopsis, and, more generally, they demonstrate that novel developmental gene
      function may arise solely by the modification of cis-regulatory sequences.

PMID- 11290295
TI  - Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase
      (NIK).
AB  - We have previously shown that the Drosophila Ste20 kinase encoded by misshapen
      (msn) is an essential gene in Drosophila development. msn function is required to
      activate the Drosophila c-Jun N-terminal kinase (JNK), basket (Bsk), to promote
      dorsal closure of the Drosophila embryo. Later in development, msn expression is
      required in photoreceptors in order for their axons to project normally. A
      mammalian homolog of msn, the NCK-interacting kinase (NIK) (recently renamed to
      mitogen-activated protein kinase kinase kinase kinase 4; Map4k4), has been shown
      to activate JNK and to bind the SH3 domains of the SH2/SH3 adapter NCK. To
      determine whether NIK also plays an essential role in mammalian development, we
      created mice deficient in NIK by homologous recombination at the Nik gene. Nik(-/
      ) mice die postgastrulation between embryonic day (E) 9.5 and E10.5. The most
      striking phenotype in Nik(-/-) embryos is the failure of mesodermal and
      endodermal cells that arise from the anterior end of the primitive streak (PS) to
      migrate to their correct location. As a result Nik(-/- )embryos fail to develop
      somites or a hindgut and are truncated posteriorly. Interestingly, chimeric
      analysis demonstrated that NIK has a cell nonautonomous function in stimulating
      migration of presomitic mesodermal cells away from the PS and a second cell
      autonomous function in stimulating the differentiation of presomitic mesoderm
      into dermomyotome. These findings indicate that despite the large number of Ste20
      kinases in mammalian cells, members of this family play essential nonredundant
      function in regulating specific signaling pathways. In addition, these studies
      provide evidence that the signaling pathways regulated by these kinases are
      diverse and not limited to the activation of JNK because mesodermal and somite
      development are not perturbed in JNK1-, and JNK2-deficient mice.

PMID- 11290296
TI  - Induced repatterning of type XVIII collagen expression in ureter bud from kidney
      to lung type: association with sonic hedgehog and ectopic surfactant protein C.
AB  - Epithelial-mesenchymal tissue interactions regulate the formation of signaling
      centers that play a role in the coordination of organogenesis, but it is not
      clear how their activity leads to differences in organogenesis. We report that
      type XVIII collagen, which contains both a frizzled and an endostatin domain, is
      expressed throughout the respective epithelial bud at the initiation of lung and
      kidney organogenesis. It becomes localized to the epithelial tips in the lung
      during the early stages of epithelial branching, while its expression in the
      kidney is confined to the epithelial stalk region and is lost from the nearly
      formed ureter tips, thus displaying the reverse pattern to that in the lung. In
      recombinants, between ureter bud and lung mesenchyme, type XVIII collagen
      expression pattern in the ureter bud shifts from the kidney to the lung type,
      accompanied by a shift in sonic hedgehog expression in the epithelium. The lung
      mesenchyme is also sufficient to induce ectopic lung surfactant protein C
      expression in the ureter bud. Moreover, the shift in type XVIII collagen
      expression is associated with changes in ureter development, thus resembling
      aspects of early lung type epigenesis in the recombinants. Respecification of
      collagen is necessary for the repatterning process, as type XVIII collagen
      antibody blocking had no effect on ureter development in the intact kidney,
      whereas it reduced the number of epithelial tips in the lung and completely
      blocked ureter development with lung mesenchyme. Type XVIII collagen antibody
      blocking also led to a notable reduction in the expression of Wnt2, which is
      expressed in the lung mesenchyme but not in that of the kidney, suggesting a
      regulatory interaction between this collagen and Wnt2. Respecification also
      occurred in a chimeric organ containing the ureter bud and both kidney and lung
      mesenchymes, indicating that the epithelial tips can integrate the morphogenetic
      signals independently. A glial cell line-derived neurotrophic factor signal
      induces loss of type XVIII collagen from the ureter tips and renders the ureter
      bud competent for repatterning by lung mesenchyme-derived signals. Our data
      suggest that differential organ morphogenesis is regulated by an intra-organ
      patterning process that involves coordination between inductive signals and
      matrix molecules, such as type XVIII collagen.

PMID- 11290297
TI  - Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy
      and requirement for maintenance but not initiation of Hox gene expression.
AB  - Polycomb group genes were identified as a conserved group of genes whose products
      are required in multimeric complexes to maintain spatially restricted expression
      of Hox cluster genes. Unlike in Drosophila, in mammals Polycomb group (PcG) genes
      are represented as highly related gene pairs, indicative of duplication during
      metazoan evolution. Mel18 and Bmi1 are mammalian homologs of Drosophila Posterior
      sex combs. Mice deficient for Mel18 or Bmi1 exhibit similar posterior
      transformations of the axial skeleton and display severe immune deficiency,
      suggesting that their gene products act on overlapping pathways/target genes.
      However unique phenotypes upon loss of either Mel18 or Bmi1 are also observed. We
      show using embryos doubly deficient for Mel18 and Bmi1 that Mel18 and Bmi1 act in
      synergy and in a dose-dependent and cell type-specific manner to repress Hox
      cluster genes and mediate cell survival of embryos during development. In
      addition, we demonstrate that Mel18 and Bmi1, although essential for maintenance
      of the appropriate expression domains of Hox cluster genes, are not required for
      the initial establishment of Hox gene expression. Furthermore, we show an
      unexpected requirement for Mel18 and Bmi1 gene products to maintain stable
      expression of Hox cluster genes in regions caudal to the prospective anterior
      expression boundaries during subsequent development.

PMID- 11290298
TI  - Hedgehog signaling patterns the tracheal branches.
AB  - The elaborate branching pattern of the Drosophila tracheal system originates from
      ten tracheal placodes on both sides of the embryo, each consisting of about 80
      cells. Simultaneous cell migration from each tracheal pit in six different
      directions gives rise to the stereotyped branching pattern. Each branch contains
      a fixed number of cells. Previous work has shown that in the dorsoventral axis,
      localized activation of the Dpp, Wnt and EGF receptor (DER) pathways, subdivides
      the tracheal pit into distinct domains. We present the role of the Hedgehog (Hh)
      signaling system in patterning the tracheal branches. Hh is expressed in
      segmental stripes abutting the anterior border of the tracheal placodes.
      Induction of patched expression, which results from activation by Hh,
      demonstrates that cells in the anterior half of the tracheal pit are activated.
      In hh-mutant embryos migration of all tracheal branches is absent or stalled.
      These defects arise from a direct effect of Hh on tracheal cells, rather than by
      indirect effects on patterning of the ectoderm. Tracheal cell migration could be
      rescued by expressing Hh only in the tracheal cells, without rescuing the
      ectodermal defects. Signaling by several pathways, including the Hh pathway, thus
      serves to subdivide the uniform population of tracheal cells into distinct cell
      types that will subsequently be recruited into the different branches.

PMID- 11290299
TI  - Molecular and functional evidence for early divergence of an endothelin-like
      system during metazoan evolution: analysis of the Cnidarian, hydra.
AB  - A novel putative endothelin-converting enzyme (ECE) has been cloned from hydra, a
      freshwater invertebrate that belongs to the second oldest phylum of the animal
      kingdom. As an integral component of the endothelin system, vertebrate ECE
      functions in the activation of endothelin (ET) peptides. Vertebrate ETs are (1)
      the most potent vasoconstrictors known in mammals; and (2) function as essential
      signaling ligands during development of tissues derived from neural crest cells.
      To date, only a limited number of immunocytochemical studies have suggested the
      presence of endothelin-like peptides in invertebrates. Based on structural and
      functional analyses, we present evidence for a functional endothelin-like system
      in hydra that is involved in both muscle contraction and developmental processes.
      These findings indicate the broad use of endothelin systems in metazoans and also
      indicate that this type of signaling system arose early in evolution even before
      divergence of protostomes and deuterostomes.

PMID- 11290300
TI  - Secreted FGFR3, but not FGFR1, inhibits lens fiber differentiation.
AB  - The vertebrate lens has a distinct polarity with cuboidal epithelial cells on the
      anterior side and differentiated fiber cells on the posterior side. It has been
      proposed that the anterior-posterior polarity of the lens is imposed by factors
      present in the ocular media surrounding the lens (aqueous and vitreous humor).
      The differentiation factors have been hypothesized to be members of the
      fibroblast growth factor (FGF) family. Though FGFs have been shown to be
      sufficient for induction of lens differentiation both in vivo and in vitro, they
      have not been demonstrated to be necessary for endogenous initiation of fiber
      cell differentiation. To test this possibility, we have generated transgenic mice
      with ocular expression of secreted self-dimerizing versions of FGFR1 (FR1) and
      FGFR3 (FR3). Expression of FR3, but not FR1, leads to an expansion of
      proliferating epithelial cells from the anterior to the posterior side of the
      lens due to a delay in the initiation of fiber cell differentiation. This delay
      is most apparent postnatally and correlates with appropriate changes in
      expression of marker genes including p57(KIP2), Maf and Prox1. Phosphorylation of
      Erk1 and Erk2 was reduced in the lenses of FR3 mice compared with nontransgenic
      mice. Though differentiation was delayed in FR3 mice, the lens epithelial cells
      still retained their intrinsic ability to respond to FGF stimulation. Based on
      these results we propose that the initiation of lens fiber cell differentiation
      in mice requires FGF receptor signaling and that one of the lens differentiation
      signals in the vitreous humor is a ligand for FR3, and is therefore likely to be
      an FGF or FGF-like factor.

PMID- 11290301
TI  - Establishment of segment polarity in the ectoderm of the leech Helobdella.
AB  - The segmented ectoderm and mesoderm of the leech arise via a stereotyped cell
      lineage from embryonic stem cells called teloblasts. Each teloblast gives rise to
      a column of primary blast cell daughters, and the blast cells generate descendant
      clones that serve as the segmental repeats of their particular teloblast lineage.
      We have examined the mechanism by which the leech primary blast cell clones
      acquire segment polarity - i.e. a fixed sequence of positional values ordered
      along the anteroposterior axis of the segmental repeat. In the O and P teloblast
      lineages, the earliest divisions of the primary blast cell segregate anterior and
      posterior cell fates along the anteroposterior axis. Using a laser microbeam, we
      ablated single cells from both o and p blast cell clones at stages when the clone
      was two to four cells in length. The developmental fate of the remaining cells
      was characterized with rhodamine-dextran lineage tracer. Twelve different progeny
      cells were ablated, and in every case the ablation eliminated the normal
      descendants of the ablated cell while having little or no detectable effect on
      the developmental fate of the remaining cells. This included experiments in which
      we specifically ablated those blast cell progeny that are known to express the
      engrailed gene, or their lineal precursors. These findings confirm and extend a
      previous study by showing that the establishment of segment polarity in the leech
      ectoderm is largely independent of cell interactions conveyed along the
      anteroposterior axis. Both intercellular signaling and engrailed expression play
      an important role in the segment polarity specification of the Drosophila embryo,
      and our findings suggest that there may be little or no conservation of this
      developmental mechanism between those two organisms.

PMID- 11290302
TI  - The Drosophila sex determination hierarchy modulates wingless and decapentaplegic
      signaling to deploy dachshund sex-specifically in the genital imaginal disc.
AB  - The integration of multiple developmental cues is crucial to the combinatorial
      strategies for cell specification that underlie metazoan development. In the
      Drosophila genital imaginal disc, which gives rise to the sexually dimorphic
      genitalia and analia, sexual identity must be integrated with positional cues, in
      order to direct the appropriate sexually dimorphic developmental program. Sex
      determination in Drosophila is controlled by a hierarchy of regulatory genes. The
      last known gene in the somatic branch of this hierarchy is the transcription
      factor doublesex (dsx); however, targets of the hierarchy that play a role in
      sexually dimorphic development have remained elusive. We show that the gene
      dachshund (dac) is differentially expressed in the male and female genital discs,
      and plays sex-specific roles in the development of the genitalia. Furthermore,
      the sex determination hierarchy mediates this sex-specific deployment of dac by
      modulating the regulation of dac by the pattern formation genes wingless (wg) and
      decapentaplegic (dpp). We find that the sex determination pathway acts cell
      autonomously to determine whether dac is activated by wg signaling, as in
      females, or by dpp signaling, as in males.

PMID- 11290303
TI  - The transcription factor Schnurri plays a dual role in mediating Dpp signaling
      during embryogenesis.
AB  - Decapentaplegic (Dpp), a homolog of vertebrate bone morphogenic protein 2/4, is
      crucial for embryonic patterning and cell fate specification in Drosophila. Dpp
      signaling triggers nuclear accumulation of the Smads Mad and Medea, which affect
      gene expression through two distinct mechanisms: direct activation of target
      genes and relief of repression by the nuclear protein Brinker (Brk). The zinc
      finger transcription factor Schnurri (Shn) has been implicated as a co-factor for
      Mad, based on its DNA-binding ability and evidence of signaling dependent
      interactions between the two proteins. A key question is whether Shn contributes
      to both repression of brk as well as to activation of target genes. We find that
      during embryogenesis, brk expression is derepressed in shn mutants. However,
      while Mad is essential for Dpp-mediated repression of brk, the requirement for
      shn is stage specific. Analysis of brk; shn double mutants reveals that
      upregulation of brk does not account for all aspects of the shn mutant phenotype.
      Several Dpp target genes are expressed at intermediate levels in double mutant
      embryos, demonstrating that shn also provides a brk-independent positive input to
      gene activation. We find that Shn-mediated relief of brk repression establishes
      broad domains of gene activation, while the brk-independent input from Shn is
      crucial for defining the precise limits and levels of Dpp target gene expression
      in the embryo.

PMID- 11290304
TI  - Drosophila OVO regulates ovarian tumor transcription by binding unusually near
      the transcription start site.
AB  - Evolutionarily conserved ovo loci encode developmentally regulated, sequence
      specific, DNA-binding, C(2)H(2)-zinc-finger proteins required in the germline and
      epidermal cells of flies and mice. The direct targets of OVO activity are not
      known. Genetic experiments suggest that ovo acts in the same regulatory network
      as ovarian tumor (otu), but the relative position of these genes in the pathway
      is controversial. Three OVO-binding sites exist in a compact regulatory region
      that controls germline expression of the otu gene. Interestingly, the strongest
      OVO-binding site is very near the otu transcription start, where basal
      transcriptional complexes must function. Loss-of-function, gain-of-function and
      promoter swapping constructs demonstrate that OVO binding near the transcription
      start site is required for OVO-dependent otu transcription in vivo. These data
      unambiguously identify otu as a direct OVO target gene and raise the tantalizing
      possibility that an OVO site, at the location normally occupied by basal
      components, functions as part of a specialized core promoter.

PMID- 11290305
TI  - Ras controls growth, survival and differentiation in the Drosophila eye by
      different thresholds of MAP kinase activity.
AB  - Ras mediates a plethora of cellular functions during development. In the
      developing eye of Drosophila, Ras performs three temporally separate functions.
      In dividing cells, it is required for growth but is not essential for cell cycle
      progression. In postmitotic cells, it promotes survival and subsequent
      differentiation of ommatidial cells. In the present paper, we have analyzed the
      different roles of Ras during eye development by using molecularly defined
      complete and partial loss-of-function mutations of Ras. We show that the three
      different functions of Ras are mediated by distinct thresholds of MAPK activity.
      Low MAPK activity prolongs cell survival and permits differentiation of R8
      photoreceptor cells while high or persistent MAPK activity is sufficient to
      precociously induce R1-R7 photoreceptor differentiation in dividing cells.

PMID- 11290306
TI  - Orc mutants arrest in metaphase with abnormally condensed chromosomes.
AB  - The origin recognition complex (ORC) is a six subunit complex required for
      eukaryotic DNA replication initiation and for silencing of the heterochromatic
      mating type loci in Saccharomyces cerevisiae. Our discovery of the Drosophila ORC
      complex concentrated in the centric heterochromatin of mitotic cells in the early
      embryo and its interactions with heterochromatin protein 1 (HP-1) lead us to
      speculate that ORC may play some general role in chromosomal folding. To explore
      the role of ORC in chromosomal condensation, we have identified a mutant of
      subunit 5 of the Drosophila melanogaster origin recognition complex (Orc5) and
      have characterized the phenotypes of both the Orc5 and the previously identified
      Orc2 mutant, k43. Both Orc mutants died at late larval stages and surprisingly,
      despite a reduced number of S-phase cells, an increased fraction of cells were
      also detected in mitosis. For this latter population of cells, Orc mutants arrest
      in a defective metaphase with shorter and thicker chromosomes that fail to align
      at the metaphase plate within a poorly assembled mitotic spindle. In addition,
      sister chromatid cohesion was frequently lost. PCNA and MCM4 mutants had similar
      phenotypes to Orc mutants. We propose that DNA replication defects trigger the
      mitotic arrest, due to the fact that frequent fragmentation was observed. Thus,
      cells have a mitotic checkpoint that senses chromosome integrity. These studies
      also suggest that the density of functional replication origins and completion of
      S phase are requirements for proper chromosomal condensation.

PMID- 11290307
TI  - The spatial control of Torso RTK activation: a C-terminal fragment of the Trunk
      protein acts as a signal for Torso receptor in the Drosophila embryo.
AB  - Regulated activation of receptor tyrosine kinases depends on both the presence of
      the receptors at the cell surface and on the availability of their ligands. In
      Drosophila, the torso tyrosine kinase receptor is distributed along the surface
      of the embryo but it is only activated at the poles by a diffusible extracellular
      ligand generated at each pole that is trapped by the receptor, thereby impeding
      further diffusion. Although it is known that this signal depends on the activity
      of several genes, such as torso-like and trunk, it is still unclear how is
      generated. The identification of the signal responsible for the torso receptor
      activation is an essential step towards understanding the mechanism that
      regulates the local restriction of torso signalling. Here we report that a
      fragment containing the carboxy-terminal 108 amino acids of the trunk protein
      retains trunk activity and is sufficient to activate torso signalling. We also
      show that this fragment bypasses the requirements for the other genes involved in
      the activation of the torso receptor. These results suggest that a cleaved form
      of the trunk protein acts as a signal for the torso receptor. We therefore
      propose that the restricted activation of the torso receptor is defined by the
      spatial control of the proteolytic processing of the trunk protein.

PMID- 11290308
TI  - High frequency of colonization and absence of identifiable risk factors for
      methicillin-resistant Staphylococcus aureus (MRSA)in intensive care units in
      Brazil.
AB  - Colonization of hospitalized patients with methicillin-resistant Staphylococcus
      aureus (MRSA) is of increasing concern. To evaluate this problem in Intensive
      Care Units (ICUs) in Brazil, we studied 100 patients admitted to two ICUs from
      April to June, 1997. Of the 100 patients, 70 were male, 53 were age 60 years or
      older, 55 were previously hospitalized, 78 were transferred to the ICU from other
      hospital units, 49 had received antibiotic therapy, and 66 had undergone recent
      surgery. Nasal and axillary swab cultures were obtained on admission and every 48
      hours thereafter until discharge. MRSA were identified by plating any cultured S.
      aureus on Mueller-Hinton agar containing 6 microg/ml of oxacillin. At the time of
      admission, 46 (46%) of the patients were colonized with MRSA. No associated risk
      factors for acquiring MRSA (age, previous hospitalization, prior surgery) could
      be identified. Of the 54 patients negative for MRSA on admission, 28 (52%) became
      colonized while in the ICU. Sixteen (22%) of the 74 colonized patients (colonized
      either on admission or during ICU stay) had associated respiratory or urinary
      tract infections due to MRSA, and 9 (56%) died. No correlation with special risk
      factors (invasive procedures, antibiotic use, age, chronic disease) was
      identified. MRSA occurred frequently, but there was minimal evidence of
      associated risk factors. Thus, control of MRSA cannot be accomplished by
      targeting special factors alone, but requires attention to preventing microbial
      spread in all areas. Of special concern is the high frequency of acquiring the
      organism in the ICU (52%). Education concerning the importance of hand washing,
      environmental surface cleaning, and barrier protection from infected patients is
      needed.

PMID- 11290309
TI  - Multicenter evaluation of resistance patterns of Klebsiella pneumoniae,
      Escherichia coli, Salmonella spp and Shigella spp isolated from clinical
      specimens in Brazil: RESISTNET Surveillance Program.
AB  - Surveillance programs are essential to detect the increase of antimicrobial
      resistance, and several different programs are being conducted in many countries.
      The RESISTNET is a surveillance program for bacterial resistance against several
      antimicrobial agents initiated in 1998 among Latin American countries. In Brazil,
      several centers were invited to join this surveillance and a total of 11 centers
      (6 from Sao Paulo and 5 from other states) participated in the study. All results
      were analyzed using the WHONET program. A total of 894 Escherichia coli, 386
      Klebsiella pneumoniae, 70 Shigella spp and 57 Salmonella spp strains were
      analyzed in this study from April, 1998, to April, 1999. Susceptibility testing
      was performed by the disk diffusion method using NCCLS 1998 guidelines for
      several different drugs. For all strains, imipenem was the most effective drug
      (100% of the strains were susceptible). Klebsiella pneumoniae presented a high
      resistance rate to ampicillin (96.4%). The rate of probable ESBL producers among
      K. pneumoniae strains was 36.3%, most of them being isolated from catheters
      (58.8%). Among all Escherichia coli strains analyzed, the highest resistance rate
      was found for trimethoprim/sulfamethoxazole (46.9%) and the majority of the
      resistant strains were isolated from urine samples (47.8%). Among Salmonella spp,
      the resistance rates were low for all antibiotics tested. For Shigella spp
      strains there was a high resistance to trimethoprim/sulfamethoxazole (80.0%). No
      resistance to ceftriaxone was observed in these strains. Surveillance of
      antimicrobial resistance is critical for the successful management of infectious
      diseases. The results of this survey show significant resistance rates among
      these bacteria which are responsible for several types of human infections.

PMID- 11290310
TI  - Community acquired pneumonia among pediatric outpatients in Salvador, Northeast
      Brazil, with emphasis on the role of pneumococcus.
AB  - Pneumonia is one of the leading causes of hospitalization and death among
      children in developing countries, and mortality due to pneumonia has been
      associated with S. pneumoniae infection. This investigation was designed to
      describe the antimicrobial susceptibility and serotype patterns of pneumococcal
      strains recovered from the blood of children with community-acquired pneumonia
      (CAP) and to assess the clinical findings of pneumococcal bacteremic patients
      with pneumonia. In a 26 month prospective study, blood cultures were obtained as
      often as possible from children (<16 years of age) diagnosed with CAP in two
      emergency rooms. Antimicrobial drug susceptibility tests and serotyping were
      performed when pneumococcus was identified. We studied 3,431 cases and cultured
      blood samples from 65.5% of those. Pneumococcus was recovered from 0.8% of the
      blood samples. The differences in age, somnolence, wheezing and hospitalization
      among children with and without pneumococcal bacteremia were statistically
      significant. Pneumococcal bacteremia was age-related (mean 1.63 +/- 1.55; median
      0.92) and associated with somnolence and hospitalization among children with CAP.
      One strain was recovered from pleural fluid. Penicillin resistance was detected
      in 21.0% (4/19) of the strains at an intermediate level, whereas 63.0% of the
      strains were resistant to trimethoprim-sulfamethoxazole. The most common
      serotypes were 14 and 6B, and these serotypes included the resistant strains.
      Eight of our 18 isolates from blood were of types included in the heptavalent
      conjugate pneumococcal vaccine, recently licensed in the USA.

PMID- 11290311
TI  - Antimicrobial susceptibility of quinupristin/dalfopristin tested against gram
      positive cocci from Latin America: results from the global SMART (GSMART)
      surveillance study.
AB  - Gram-positive cocci are important causes of both nosocomial and community
      acquired infections, and antimicrobial resistance among these pathogens has
      become an important problem worldwide. Since resistance among these organisms can
      vary substantially by geographic location, we conducted a multicenter
      surveillance study with isolates from five Latin American countries (15 medical
      centers). Quinupristin/dalfopristin (formerly RP-59500) is a novel streptogramin
      combination with focused activity against Gram-positive cocci, many exhibiting
      emerging resistance. The in vitro activity of quinupristin/dalfopristin and 12
      other antimicrobial agents were evaluated against 1,948 strains including
      Staphylococcus aureus (747 strains), coagulase-negative staphylococci (CoNS;446
      strains), enterococci (429 strains), and various Streptococcus spp. (326
      strains). Oxacillin resistance was observed in 41% of S. aureus (MIC, <e; 2
      microg/ml or >e; 13 mm) and 40% of CoNS (MIC, <e; 0.25 microg/ml or >e; 18 mm).
      Vancomycin, teicoplanin, and quinupristin/dalfopristin (MIC(90), 0.25 - 1 mg/ml)
      remained effective against all strains, but cross-resistance was high among other
      tested drugs. The quinupristin/dalfopristin MIC(50) for Streptococcus pneumoniae
      and other streptococci was only 0.5 mg/ml (13% to 28% were penicillin-resistant;
      12% to 22% were macrolide-resistant). Enterococci demonstrated variable
      inhibition by quinupristin/dalfopristin depending upon identification and the
      susceptibility testing method used. The demonstrated quinupristin/dalfopristin
      activity against Enterococcus faecium was confirmed, but potential species
      identification errors with various commercial systems continue to confuse
      susceptibility statistics, even though some strains of E. faecium confirmed by
      PCR-based or other molecular identification techniques did have
      quinupristin/dalfopristin MICs of >e; 4 microg/ml. Most important, glycopeptide
      resistant enterococci are rapidly emerging in Latin America, and
      quinupristin/dalfopristin appears active against many of these isolates as well
      as having potency against nearly all staphylococci and streptococci tested at <e;
      2 microg/ml or having a zone diameter of >e; 16 mm. Comparisons to GSMART results
      from other continents show nearly identical quinupristin/dalfopristin activity
      for each Gram-positive species tested. These results define the role of
      quinupristin/dalfopristin in Latin American medical centers and provide a
      benchmark for future in vitro comparisons.

PMID- 11290312
TI  - Cluster of Candida parapsilosis primary bloodstream infection in a neonatal
      intensive care unit.
AB  - Candida parapsilosis is an increasingly important bloodstream pathogen in
      neonatal intensive care units (NICU). We investigated a cluster of bloodstream
      infections in a NICU to determine whether nosocomial transmission occurred.
      During a 3-day period, 3 premature infants hospitalized in the same unit
      presented with sepsis caused by C. parapsilosis. Electrophoretic karyotype of the
      organisms was performed by using pulsed field gel electrophoresis in a countour
      clamped homogeneous electric field system. The isolate from 1 newborn could not
      be typed, and the isolates from the remaining 2 infants had identical patterns.
      All 3 cases are described. We conclude that nosocomial transmission of C.
      parapsilosis occurred and that neonates under intensive care may represent a risk
      group for this pathogen.

PMID- 11290313
TI  - Two family members with a syndrome of headache and rash caused by human
      parvovirus B19.
AB  - Human parvovirus B19 infection can cause erythema infectiosum (EI) and several
      other clinical presentations. Central nervous system (CNS) involvement is rare,
      and only a few reports of encephalitis and aseptic meningitis have been
      published. Here, we describe 2 cases of B19 infection in a family presenting
      different clinical features. A 30 year old female with a 7-day history of
      headache, malaise, myalgias, joint pains, and rash was seen. Physical examination
      revealed a maculopapular rash on the patient's body, and arthritis of the hands.
      She completely recovered in 1 week. Two days before, her 6 year old son had been
      admitted to a clinic with a 1-day history of fever, headache, abdominal pain and
      vomiting. On admission, he was alert, and physical examination revealed neck
      stiffness, Kerning and Brudzinski signs, and a petechial rash on his trunk and
      extremities. Cerebrospinal fluid analysis was normal. He completely recovered in
      5 days. Acute and convalescent sera of both patients were positive for specific
      IgM antibody to B19. Human parvovirus B19 should be considered in the
      differential diagnosis of aseptic meningitis, particularly during outbreaks of
      erythema infectiosum. The disease may mimic meningococcemia and bacterial
      meningitis.

PMID- 11290314
TI  - Enterococcus faecalis resistant to vancomycin and teicoplanin (VanA phenotype)
      isolated from a bone marrow transplanted patient in Brazil.
AB  - We report for the first time in Brazil, a patient from whom an Enterococcus
      faecalis VanA phenotype was isolated. Glycopeptide resistance is not commonly
      observed in Enterococcus faecalis, so this finding is of great concern since this
      species is responsible for 90% of enterococcal infections in Brazil. The isolate
      was recovered from a surveillance rectal swab culture from a patient with acute
      lymphocytic leukemia (ALL). Identification to the species level was performed by
      conventional biochemical tests and Vitek GPI cards. Antimicrobial susceptibility
      testing was evaluated by use of broth microdilution and Etest (AB BIODISK, Solna,
      Sweden) methods. The isolate was identified as E. faecalis and was considered
      resistant to both vancomycin (MIC, > 256 microg/mL) and teicoplanin (MIC, 256
      microg/mL). The isolate also showed high level resistance to gentamicin and
      streptomycin (MICs, > 1024 microg/mL), but was considered susceptible to
      ampicillin (MIC, 4 microg/mL). Although the frequency of enterococcal infections
      is very low in most Latin America countries, the finding of glycopeptide (VanA)
      resistance in E. faecalis increases concern about apreading antimicrobial
      resistance in this region.

PMID- 11290315
TI  - Control of spread of microorganisms in the hospital--back to the basics of hand
      washing and glove use.

PMID- 11290316
TI  - Twisted perspective: new insights into extracellular modulation of BMP signaling
      during development.

PMID- 11290317
TI  - Cell death inhibition: keeping caspases in check.

PMID- 11290318
TI  - Glycosylation, immunity, and autoimmunity.

PMID- 11290319
TI  - The ribosome in focus.

PMID- 11290320
TI  - Histone acetyltransferase complexes stabilize swi/snf binding to promoter
      nucleosomes.
AB  - To investigate the function of SWI/SNF in site-specific chromatin remodeling at
      promoters, we have used a purified system to analyze its distribution, function,
      and retention following recruitment by a sequence-specific transcription
      activator. Activator recruitment of SWI/SNF bound the complex to promoter
      proximal nucleosomes and led to localized nucleosome disruption. However,
      retention of SWI/SNF on the promoter required either the continued binding of the
      transcription activator or acetylated histones. Histone acetylation by either the
      SAGA or NuA4 HAT complexes increased the retention of SWI/SNF on the promoter.
      These data illustrate a functional link between HAT complexes and the SWI/SNF
      chromatin remodeling complex and provide a mechanistic basis for the ordered
      recruitment of these complexes.

PMID- 11290321
TI  - Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene.
AB  - Maintenance of genomic methylation patterns in mammalian somatic cells depends on
      DNA methyltransferase-1 (Dnmt1). Mouse oocytes and preimplantation embryos lack
      Dnmt1 but express a variant of this protein called Dnmt1o. We eliminated Dnmt1o
      by deletion of the oocyte-specific promoter and first exon from the Dnmt1 locus.
      Homozygous animals were normal, but most heterozygous fetuses of homozygous
      females died during the last third of gestation. Although genomic methylation
      patterns were established normally in Dnmt1o-deficient oocytes, embryos derived
      from such oocytes showed a loss of allele-specific expression and methylation at
      certain imprinted loci. Transient nuclear localization of Dnmt1o in 8-cell
      embryos suggests that this variant of Dnmt1 provides maintenance
      methyltransferase activity specifically at imprinted loci during the fourth
      embryonic S phase.

PMID- 11290322
TI  - Modulation of a transcription factor counteracts heterochromatic gene silencing
      in Drosophila.
AB  - Variegation is a common feature of gene silencing phenomena, yet the basis for
      stochastic on/off expression is unknown. We used a conditional system that allows
      probing of heterochromatin at a reporter GFP gene by altering GAL4 transcription
      factor levels during Drosophila eye development. Surprisingly, the frequency of
      gene silencing is exquisitely sensitive to GAL4 levels, as though binding site
      occupancy affects the silenced state. The silent state is plastic, as spontaneous
      derepression occasionally occurs in both mitotically active and differentiating
      cells. By simultaneously assaying expression of a nearby gene, we further show
      that the size of an activated region within heterochromatin is small. We propose
      that variegation occurs because heterochromatin inhibits the transient exposure
      of factor binding sites.

PMID- 11290323
TI  - A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in
      cooperation with Pitx homeoproteins.
AB  - The pituitary gland has provided unique insight into molecular mechanisms and
      regulatory factors controlling both differentiation and gene transcription. We
      identified Tpit, a novel T box factor only present in the two pituitary POMC
      expressing lineages, the corticotrophs and melanotrophs, and apparently in no
      other tissue, including hypothalamic POMC neurons. In pituitary cells, Tpit
      activation of POMC gene transcription requires cooperation with Pitx1, the two
      factors binding to contiguous sites within the same regulatory element. In gain
      of-function experiments, Tpit induces POMC expression in undifferentiated
      pituitary cells, indicating that it can initiate differentiation into POMC
      expressing lineages. TPIT gene mutations were found in patients with isolated
      deficiency of pituitary POMC-derived ACTH, in support of an essential role of
      Tpit for differentiation of the pituitary POMC lineage.

PMID- 11290324
TI  - Groucho-mediated transcriptional repression establishes progenitor cell pattern
      and neuronal fate in the ventral neural tube.
AB  - The pattern of neuronal specification in the ventral neural tube is controlled by
      homeodomain transcription factors expressed by neural progenitor cells, but no
      general logic has emerged to explain how these proteins determine neuronal fate.
      We show that most of these homeodomain proteins possess a conserved eh1 motif
      that mediates the recruitment of Gro/TLE corepressors. The eh1 motif underlies
      the function of these proteins as repressors during neural patterning in vivo.
      Inhibition of Gro/TLE-mediated repression in vivo results in a deregulation of
      cell pattern in the neural tube. These results imply that the pattern of
      neurogenesis in the neural tube is achieved through the spatially controlled
      repression of transcriptional repressors-a derepression strategy of neuronal fate
      specification.

PMID- 11290325
TI  - Male-to-female sex reversal in mice lacking fibroblast growth factor 9.
AB  - Fgfs direct embryogenesis of several organs, including the lung, limb, and
      anterior pituitary. Here we report male-to-female sex reversal in mice lacking
      Fibroblast growth factor 9 (Fgf9), demonstrating a novel role for FGF signaling
      in testicular embryogenesis. Fgf9(-/-) mice also exhibit lung hypoplasia and die
      at birth. Reproductive system phenotypes range from testicular hypoplasia to
      complete sex reversal, with most Fgf9(-/-) XY reproductive systems appearing
      grossly female at birth. Fgf9 appears to act downstream of Sry to stimulate
      mesenchymal proliferation, mesonephric cell migration, and Sertoli cell
      differentiation in the embryonic testis. While Sry is found only in some mammals,
      Fgfs are highly conserved. Thus, Fgfs may function in sex determination and
      reproductive system development in many species.

PMID- 11290326
TI  - WNT signals control FGF-dependent limb initiation and AER induction in the chick
      embryo.
AB  - A regulatory loop between the fibroblast growth factors FGF-8 and FGF-10 plays a
      key role in limb initiation and AER induction in vertebrate embryos. Here, we
      show that three WNT factors signaling through beta-catenin act as key regulators
      of the FGF-8/FGF-10 loop. The Wnt-2b gene is expressed in the intermediate
      mesoderm and the lateral plate mesoderm in the presumptive chick forelimb region.
      Cells expressing Wnt-2b are able to induce Fgf-10 and generate an extra limb when
      implanted into the flank. In the presumptive hindlimb region, another Wnt gene,
      Wnt-8c, controls Fgf-10 expression, and is also capable of inducing ectopic limb
      formation in the flank. Finally, we also show that the induction of Fgf-8 in the
      limb ectoderm by FGF-10 is mediated by the induction of Wnt-3a. Thus, three WNT
      signals mediated by beta-catenin control both limb initiation and AER induction
      in the vertebrate embryo.

PMID- 11290327
TI  - Structural mechanism for rifampicin inhibition of bacterial rna polymerase.
AB  - Rifampicin (Rif) is one of the most potent and broad spectrum antibiotics against
      bacterial pathogens and is a key component of anti-tuberculosis therapy, stemming
      from its inhibition of the bacterial RNA polymerase (RNAP). We determined the
      crystal structure of Thermus aquaticus core RNAP complexed with Rif. The
      inhibitor binds in a pocket of the RNAP beta subunit deep within the DNA/RNA
      channel, but more than 12 A away from the active site. The structure, combined
      with biochemical results, explains the effects of Rif on RNAP function and
      indicates that the inhibitor acts by directly blocking the path of the elongating
      RNA when the transcript becomes 2 to 3 nt in length.

PMID- 11290328
TI  - Control of cell shape in bacteria: helical, actin-like filaments in Bacillus
      subtilis.
AB  - In the absence of an overt cytoskeleton, the external cell wall of bacteria has
      traditionally been assumed to be the primary determinant of cell shape. In the
      Gram-positive bacterium Bacillus subtilis, two related genes, mreB and mbl, were
      shown to be required for different aspects of cell morphogenesis. Subcellular
      localization of the MreB and Mbl proteins revealed that each forms a distinct
      kind of filamentous helical structure lying close to the cell surface. The
      distribution of the proteins in different species of bacteria, and the similarity
      of their sequence to eukaryotic actins, suggest that the MreB-like proteins have
      a cytoskeletal, actin-like role in bacterial cell morphogenesis.

PMID- 11290329
TI  - Clasps are CLIP-115 and -170 associating proteins involved in the regional
      regulation of microtubule dynamics in motile fibroblasts.
AB  - CLIP-170 and CLIP-115 are cytoplasmic linker proteins that associate specifically
      with the ends of growing microtubules and may act as anti-catastrophe factors.
      Here, we have isolated two CLIP-associated proteins (CLASPs), which are
      homologous to the Drosophila Orbit/Mast microtubule-associated protein. CLASPs
      bind CLIPs and microtubules, colocalize with the CLIPs at microtubule distal
      ends, and have microtubule-stabilizing effects in transfected cells. After serum
      induction, CLASPs relocalize to distal segments of microtubules at the leading
      edge of motile fibroblasts. We provide evidence that this asymmetric CLASP
      distribution is mediated by PI3-kinase and GSK-3 beta. Antibody injections
      suggest that CLASP2 is required for the orientation of stabilized microtubules
      toward the leading edge. We propose that CLASPs are involved in the local
      regulation of microtubule dynamics in response to positional cues.

PMID- 11290330
TI  - Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera
      toxin.
AB  - Cholera toxin is assembled from two subunits in the periplasm of Vibrio cholerae
      and disassembled in the analogous compartment of target cells, the lumen of the
      endoplasmic reticulum (ER), before a fragment of it, the A1 chain, is transported
      into the cytosol. We show that protein disulfide isomerase (PDI) in the ER lumen
      functions to disassemble and unfold the toxin once its A chain has been cleaved.
      PDI acts as a redox-driven chaperone; in the reduced state, it binds to the A
      chain and in the oxidized state it releases it. Our results explain the pathway
      of cholera toxin, suggest a role for PDI in retrograde protein transport into the
      cytosol, and indicate that PDI can act as a novel type of chaperone, whose
      binding and release of substrates is regulated by a redox, rather than an ATPase,
      cycle.

PMID- 11290331
TI  - Early transcription and silencing of cytokine genes underlie polarization of T
      helper cell subsets.
AB  - Naive CD4+ T cells activated through TCR/CD28 under Th1 or Th2 conditions
      expressed canonical cytokine patterns irrespective of cell division. Only cells
      that had divided fewer than four times were capable of reexpressing alternative
      cytokines when restimulated under opposing conditions. Although T cells
      transcribed both IFN-gamma and IL-4 within hours in a Stat4-/Stat6-independent
      manner, neither T-bet nor GATA-3 was induced optimally without Stat signals, and
      polarized cytokine expression was not sustained. Cytokine genes were positioned
      apart from heterochromatin in resting T cell nuclei, consistent with rapid
      expression. After polarization, the majority of silenced cytokine alleles were
      repositioned to heterochromatin. Naive T cells transit through sequential stages
      of cytokine activation, commitment, silencing, and physical stabilization during
      polarization into differentiated effector subsets.

PMID- 11290332
TI  - IKKbeta is essential for protecting T cells from TNFalpha-induced apoptosis.
AB  - Transcription factor NF-kappaB, whose activation depends on the IKKbeta catalytic
      subunit of the IkappaB kinase, was assigned with both anti- and proapoptotic
      functions in T lymphocytes. To critically evaluate these functions, we
      transferred Ikkbeta-/- or wild-type (wt) fetal liver (FL) stem cells into
      lethally irradiated mice. Ikkbeta-/- radiation chimeras show thymic rudiments,
      aberrant lymphoid organs, and absence of T cells. T lymphopoiesis is rescued when
      Ikkbeta-/- stem cells are cotransferred with wt bone marrow, suggesting that
      IKKbeta may mediate its lymphopoietic function via extrinsic factors. However,
      almost normal development of Ikkbeta-/- T cells is observed upon removal of type
      1 TNFalpha receptor, indicating that TNFalpha signaling accounts for the absence
      of Ikkbeta-/- T cells. Indeed, Ikkbeta-/- radiation chimeras exibit elevated
      circulating TNFalpha, and Ikkbeta-/- thymocytes display increased TNFalpha
      sensitivity.

PMID- 11290333
TI  - The crystal structures of K(bm1) and K(bm8) reveal that subtle changes in the
      peptide environment impact thermostability and alloreactivity.
AB  - The K(bm1) and K(bm8) natural mutants of the murine MHC class I molecule H-2K(b)
      were originally identified by allograft rejection. They also bind viral peptides
      VSV8 and SEV9 with high affinity, but their peptide complexes have substantially
      decreased thermostability, and the K(bm1) complexes do not elicit alloreactive T
      cell responses. Crystal structures of the four mutant complexes at 1.7-1.9 A
      resolution are similar to the corresponding wild-type K(b) structures, except in
      the vicinity of the mutated residues, which alter the electrostatic potential,
      topology, hydrogen bonding, and local water structure of the peptide binding
      groove. Thus, these natural K(b) mutations define the minimal perturbations in
      the peptide environment that alter antigen presentation to T cells and abolish
      alloreactivity.

PMID- 11290334
TI  - A kinetic window constricts the T cell receptor repertoire in the thymus.
AB  - To characterize the ligand binding properties of a naive T cell repertoire
      capable of responding to a foreign antigen, we analyzed T cell populations from T
      cell receptor (TCR) beta transgenic mice using a novel, single cell peptide/major
      histocompatibility complex (MHC) tetramer dissociation assay. The largely
      CD4+CD8(-/low) antigen-specific thymocyte repertoire exhibited a broad, bimodal
      distribution of tetramer binding half-lives (t(1/2)s), with a significant
      underrepresentation in the intermediate half-life range in which the majority of
      the peripheral repertoire lies. Thus, cells with the potential to bind foreign
      antigen with the lowest and highest stability are likely to be selectively
      removed from the repertoire prior to their establishment in the periphery. These
      studies provide direct evidence that thymic selection biases the naive peripheral
      T cell repertoire toward TCR-ligand interactions that fall within a moderate half
      life "window."

PMID- 11290336
TI  - A cell surface amine oxidase directly controls lymphocyte migration.
AB  - Lymphocytes leave the blood using a sequential adhesion cascade. Vascular
      adhesion molecule-1 (VAP-1) is a surface-expressed endothelial glycoprotein,
      which belongs to a distinct subgroup of monoamine oxidases. We show here that
      catalytic activity of VAP-1 on primary endothelial cells directly regulates
      lymphocyte rolling under defined laminar shear. VAP-1 seems to bind to a primary
      amino group presented on the lymphocyte surface and oxidatively deaminate it in a
      reaction, which results in the formation of a transient covalent bond between the
      two cell types. Instead, soluble reaction products (aldehydes and hydrogen
      peroxide) are not needed for the VAP-1-dependent rolling. Enzymatic regulation of
      lymphocyte adhesion to endothelium provides a previously unrecognized rapid way
      of controlling the extravasation process.

PMID- 11290335
TI  - Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal
      strength.
AB  - Notch signaling regulates cell fate decisions in multiple lineages. We
      demonstrate in this report that retroviral expression of activated Notch1 in
      mouse thymocytes abrogates differentiation of immature CD4+CD8+ thymocytes into
      both CD4 and CD8 mature single-positive T cells. The ability of Notch1 to inhibit
      T cell development was observed in vitro and in vivo with both normal and TCR
      transgenic thymocytes. Notch1-mediated developmental arrest was dose dependent
      and was associated with impaired thymocyte responses to TCR stimulation. Notch1
      also inhibited TCR-mediated signaling in Jurkat T cells. These data indicate that
      constitutively active Notch1 abrogates CD4+ and CD8+ maturation by interfering
      with TCR signal strength and provide an explanation for the physiological
      regulation of Notch expression during thymocyte development.

PMID- 11290337
TI  - IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells
      and involved in chromosome 1q21 abnormalities in B cell malignancy.
AB  - Abnormalities of chromosome 1q21 are common in B cell malignancies, but their
      target genes are largely unknown. By cloning the breakpoints of a (1;14)
      (q21;q32) chromosomal translocation in a myeloma cell line, we have identified
      two novel genes, IRTA1 and IRTA2, encoding cell surface receptors homologous to
      the Fc and inhibitory receptor families. Both genes are selectively expressed in
      mature B cells: IRTA1 in marginal zone B cells and IRTA2 in centrocytes, marginal
      zone B cells, and immunoblasts. As a result of the t(1;14), IRTA1 is fused to the
      immunoglobulin Calpha domain to produce a chimeric IRTA1/Calpha fusion protein.
      In tumor cell lines with 1q21 abnormalities, IRTA2 expression is deregulated.
      Thus, IRTA1 and IRTA2 are novel immunoreceptors implicated in B cell development
      and lymphomagenesis.

PMID- 11290338
TI  - CD62L is required on effector cells for local interactions in the CNS to cause
      myelin damage in experimental allergic encephalomyelitis.
AB  - Adhesion molecules are believed to facilitate infiltration of leukocytes into the
      CNS of mice with experimental allergic encephalomyelitis (EAE). The role of the
      adhesion molecule CD62L (L-selectin) in the immunopathology of EAE is not known.
      To study this, we crossed CD62L-deficient mice with myelin basic protein-specific
      TCR (MBP-TCR) transgenic mice. CD62L-deficient MBP-TCR transgenic mice failed to
      develop antigen-induced EAE, and, despite the presence of leukocyte infiltration,
      damage to myelin in the CNS was not seen. EAE could, however, be induced in CD62L
      deficient mice upon adoptive transfer of wild-type macrophages. Our results
      suggest that CD62L is not required for activation of autoimmune CD4 T cells but
      is important for the final destructive function of effector cells in the CNS and
      support a novel mechanism whereby CD62L expressed on effector cells is important
      in mediating myelin damage.

PMID- 11290339
TI  - CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and
      calreticulin.
AB  - Complexes of the heat shock protein gp96 and antigenic peptides are taken up by
      antigen-presenting cells and presented by MHC class I molecules. In order to
      explain the unusual efficiency of this process, the uptake of gp96 had been
      postulated to occur through a receptor, identified recently as CD91. We show here
      that complexes of peptides with heat shock proteins hsp90, calreticulin, and
      hsp70 are also taken up by macrophages and dendritic cells and re-presented by
      MHC class I molecules. All heat shock proteins utilize the CD91 receptor, even
      though some of the proteins have no homology with each other. Postuptake
      processing of gp96-chaperoned peptides requires proteasomes and the transporters
      associated with antigen processing, utilizing the classical endogenous antigen
      presentation pathway.

PMID- 11290340
TI  - Dynamic actin polymerization drives T cell receptor-induced spreading: a role for
      the signal transduction adaptor LAT.
AB  - T cell activation induces functional changes in cell shape and cytoskeletal
      architecture. To facilitate the collection of dynamic, high-resolution images of
      activated T cells, we plated T cells on coverslips coated with antibodies to the
      T cell receptor (TCR). Using these images, we were able to quantitate the
      morphological responses of individual cells over time. Here, we show that TCR
      engagement triggers the formation and expansion of contacts bounded by
      continuously remodeled actin-rich rings. These processes are associated with the
      extension of lamellipodia and require actin polymerization, tyrosine kinase
      activation, cytoplasmic calcium increases, and LAT, an important hematopoietic
      adaptor. In addition, the maintenance of the resulting contact requires sustained
      calcium influxes, an intact microtubule cytoskeleton, and functional LAT.

PMID- 11290341
TI  - Superantigen recognition by gammadelta T cells: SEA recognition site for human
      Vgamma2 T cell receptors.
AB  - Human gammadelta T cells expressing the Vgamma2Vdelta2 antigen receptors
      recognize nonpeptide prenyl pyrophosphate and alkylamine antigens. We find that
      they also recognize staphylococcal enterotoxin A superantigens in a manner
      distinct from the recognition of nonpeptide antigens. Using chimeric and mutant
      toxins, SEA amino acid residues 20-27 were shown to be required for gammadelta
      TCR recognition of SEA. Residues at 200-207 that are critical for specific
      alphabeta TCR recognition of SEA do not affect gammadelta TCR recognition. SEA
      residues 20-27 are located in an area contiguous with the binding site of V beta
      chains. This study defines a superantigen recognition site for a gammadelta T
      cell receptor and demonstrates the differences between Vgamma2Vdelta2+ T cell
      recognition of superantigens and nonpeptide antigens.

PMID- 11290342
TI  - Innovative exposure assessment of pesticide uses for appropriate risk assessment.
      Introductory remarks.

PMID- 11290343
TI  - Could pesticide toxicology studies be more relevant to occupational risk
      assessment?
AB  - Pesticide toxicology study design has evolved from concern for oral exposure via
      food residues. The emphasis on the oral route does not generally apply to workers
      that are exposed primarily via the dermal route either handling pesticides or re
      entering treated fields. As a result numerous assumptions about how oral
      toxicology results relate to dermal exposure must be made when conducting worker
      risk assessments. These assumptions introduce a high degree of uncertainty.
      Alternative toxicology study designs are suggested to reduce uncertainty when
      assessing risk. Because the dermal route is so important to characterizing
      occupational risk, methods to improve the accuracy of dermal absorption estimates
      are suggested, including the use of human subjects to study dermal absorption.
      Additional suggestions include tailoring dermal, oral and inhalation kinetic
      study designs to reflect worker exposure dosages. Suggestions are made to
      routinely conduct a single dose toxicity study patterned after the neurotoxicity
      study design to distinguish single dose effects and NOAELs from those resulting
      from multiple doses. Finally, interspecies pharmacokinetics studies are proposed
      to determine which toxicology study regimen of dosing best reflects intermittent
      worker exposure.

PMID- 11290345
TI  - Refinement of risk assessment of dermally and intermittently exposed pesticide
      workers: a critique.
AB  - The regulatory requirements for the registration of pesticides are mainly evolved
      from concern about dietary exposure and risk, i.e. chronic oral exposure.
      Pesticide workers, however, are predominantly exposed dermally and
      intermittently. The present critique provides suggestions for improvement of
      toxicity studies to refine the risk assessment of pesticide workers. In this
      respect it is considered of utmost importance that toxicity studies (either
      toxicokinetic or toxicodynamic) should be tuned towards the anticipated exposure
      scenario. Apart from suggestions for improvement of dermal toxicokinetic and
      dynamic studies, recommendations for further research and guidance are given,
      amongst which the request for information on the robustness of in vitro dermal
      absorption studies and guidance on how to use these data. With respect to the
      intermittent exposure of pesticide workers it is recognised that both information
      on the anticipated exposure scenario as well as knowledge on the effect of
      intermittent exposure on the toxicity are needed. From a toxicological point of
      view, the setting of more than one Acceptable Operator Exposure Level (AOEL),
      covering effects that may arise after different periods of exposure, as well as
      the development of more robust acute and short term studies are strongly
      recommended.

PMID- 11290344
TI  - Critique of the paper: could pesticide toxicology studies be more relevant to
      occupational risk assessment? (by Ross et al., 2001).
AB  - The toxicology studies required for the registration of a pesticide are not
      necessarily well adapted to user safety assessment. This problem can be overcome
      in some cases by improving the guideline studies. In other cases the guidelines
      are based on animal models which are poor models for man; the most obvious
      example is rat percutaneous penetration. In other cases it may simply be
      impractical to have a model which can be extrapolated to all exposure situations.
      This is the case for intermittent exposure which is infinitely variable. The
      general conclusion is that the entire data package should be re-examined to make
      it more relevant to risk assessment.

PMID- 11290346
TI  - Probabilistic exposure assessment of operator and residential non-dietary
      exposure.
AB  - This paper discusses the potential role of probabilistic non-dietary exposure and
      risk assessment in the regulatory processes for pesticide products. Regulatory
      decisions regarding operator or consumer exposure to pesticide products have
      traditionally been based on deterministic exposure assessments. With the
      development of computer modelling and exposure databases, the submission of non
      dietary exposure probabilistic assessments are imminent. The current status of
      non-dietary probability analysis to support regulatory risk management decisions
      is provided with a case study presented to illustrate issues regarding the use of
      probability analysis for regulatory non-dietary risk assessment. The development
      of a guidance document for the use of non-dietary exposure probability analyses
      for regulatory purposes is proposed.

PMID- 11290347
TI  - Probabilistic exposure assessment of operator and residential exposure; a
      Canadian regulatory perspective.
AB  - An overview of the considerations central to selection of probabilistic versus
      deterministic approaches to assessment of operator and residential exposure are
      provided. From a regulatory perspective, the decision to use probabilistic over
      deterministic assessments should include consideration of factors such as the
      nature of the populations being assessed, including the expected duration and
      frequency of their exposures, as well as an understanding of the toxicity
      endpoints that the exposure assessment will be linked to during risk assessment.
      In situations where there is an identifiable need to characterize variability and
      uncertainty and/or quantify the exposure that will represent most of the exposed
      population, and where there are adequate data to characterize input parameters,
      probabilistic assessments may be appropriate. Issues with respect to
      probabilistic assessments for which detailed, harmonized guidance are required
      are outlined. These issues are discussed within the context of a tiered approach
      to exposure and risk assessment.

PMID- 11290348
TI  - Challenges of probabilistic assessment of operator and residential non-dietary
      exposure.
AB  - There are several challenges in the area of probabilistic exposure assessment of
      operator and residential non-dietary exposure: the proper uses of the available
      data and how to adequately understand and characterize the uncertainty in the
      assessment. The adequacy of the data can be assessed either qualitatively or
      quantitatively. If a qualitative assessment were deemed acceptable, then expert
      judgement would be the primary methodology. However, in most instances a
      quantitative assessment of adequacy will be possible and will provide more
      pertinent information. In that case statistical techniques should be used.
      Understanding and characterizing uncertainty is a separate challenge, which is
      often ignored. Instead risk assessors present characterizing the variability in
      the assessment as a characterization of both uncertainty and variability. This
      can lead to misinterpretation of the outputs of the assessment. Interpretation of
      outputs can be discussed on two levels - familiarizing the risk managers and the
      policy makers with the types of outputs resulting from a probabilistic assessment
      (graphs and/or matrices of values) as well as explaining the meanings and
      implications of the values. The burden is placed on the assessor to clearly
      reflect to the risk managers and policy makers the way on which variability and
      uncertainty were handled in the assessment. In advising the risk managers and
      policy makers, it is important to remind them of the purpose of conducting a
      probabilistic risk assessment: the probabilistic assessment allows a means to
      characterize the degrees of uncertainty and variability in terms of
      probabilities.

PMID- 11290349
TI  - An example to illustrate the potential use of probabilistic modelling to estimate
      operator exposure to pesticides.
AB  - To illustrate the potential for probabilistic simulation modelling of operator
      exposure a probabilistic model was constructed using the draft EUROPOEM II
      database. The model also incorporated actual pesticide use data. Although the
      EUROPOEM II database is not complete, and the resulting simulation has to be
      regarded as only provisional, the data were sufficient to illustrate some of the
      principles involved. The model was constructed using non-parametric empirical
      input distributions. Associations were observed in the input exposure data and
      were reflected in the model. The exposure and usage data were all variable and
      showed highly negatively skewed distributions and the technique avoided concerns
      about having to define single representative values for point estimates.
      Increasing the number of iterations improved the stability of the output, but as
      expected, resulted in higher exposures being predicted due to a combination of
      rare events. Analysis of the inputs for individual iterations giving high results
      indicated that, in this example, these were due to unrepresentatively high input
      values for inhalation exposure. Simulations that excluded these values were more
      stable and showed lower exposures, illustrating the need to ensure the validity
      of the input distributions.

PMID- 11290350
TI  - Use of probabilistic methods in exposure assessment in Germany.
AB  - Over the last two decades, quantitative risk assessment has received increasing
      attention in Germany. By now it is also acknowledged that probabilistic
      techniques in risk assessment seem to be superior to the conventional point
      estimate approach. An important prerequisite for the use of probabilistic
      techniques is seen in the provision of 'standard' probability density functions
      for key exposure factors. For such exposure factors like body weight, time
      budget, etc., default probability density functions which are representative for
      Germany need to be developed. Guidance on probabilistic modelling will be needed,
      too.

PMID- 11290351
TI  - The need for appropriate use information to refine pesticide user exposure
      assessments.
AB  - Risk assessment compares hazard information with an exposure assessment (Report
      of the OECD workshop, 1995). To characterise the risk data on the level, duration
      and frequency of exposure are required. This paper illustrates how, in the
      absence of specific usage data, structural and other data may be used to provide
      some estimates of daily work rates. The usefulness of detailed pesticide usage
      data to refine the exposure assessment is also shown. Scientifically sound usage
      data are required, and to ensure a harmonised approach requires guidelines. The
      current OECD guidelines for the collection of usage statistics (Thomas for the
      Eurostat Pesticides Statistics Taskforce, 1999) are designed to collect usage
      data for environmental reasons, but are a good basis. The adaptation of the OECD
      guidelines to collect information for user exposure assessments is discussed.

PMID- 11290352
TI  - Considerations regarding the collection of pesticide use information for
      regulatory purposes.
AB  - Proper use information is necessary to do exposure modelling in the scope of
      regulatory risk assessments. The legal regime under which the regulatory risk
      assessment is done influences the need for use information. Different legal
      regimes lead to more or less possibilities for authorities to define the exposure
      scenario to be assessed and the data to be presented by the industrial parties
      involved. The more information is required by the regulations, the less use
      information has to be gathered or guessed at by the regulatory exposure assessor.
      The value of use information is further determined by the scope of the
      assessment. A very conservative first tier (screening) assessment requires little
      information, whereas a detailed assessment of actual risks requires accurate use
      information. The scientific knowledge and available models limit the benefits of
      use information. Interesting use information has little value if there are no
      methods to account for the information in the exposure assessment, e.g. if
      relations between possible exposure determinants and exposure levels are unknown.
      The need for use information will further be dependent on the analysis of costs
      (of gathering data) versus benefits (increase in quality of the assessment). Many
      choices regarding the need for use information depend on policy choices by
      decision-makers. These decision-makers again depend on proper scientific
      information to make informed choices.

PMID- 11290353
TI  - Pesticide usage monitoring in the United Kingdom.
AB  - The last decade has seen an increasing requirement throughout the United Kingdom
      (UK) for accurate, timely information on pesticide usage to satisfy government
      legislation and provide data as part of the registration and review process of
      pesticides. These data, collected by the Ministry of Agriculture, Fisheries and
      Food's Pesticide Usage Survey Group (PUSG), provide information on current and
      past usage patterns and allow the impact of use on the environment, operator and
      consumer to be more accurately assessed from actual usage patterns rather than
      worst case scenarios. Surveys of all crops grown commercially throughout the UK
      are undertaken at regular intervals using fully stratified samples of farmers and
      growers. Data are raised to provide national estimates of use but individual data
      sets can be derived from the sample. As such, the data are therefore also
      particularly suited to incorporation into probabilistic risk assessments. The
      methodologies used by the PUSG and some example data sets from a recent survey of
      arable crops are given.

PMID- 11290355
TI  - An Australian experience of using work practices to establish an exposure model
      for shearers.
AB  - This is an example of a national regulatory approach in estimating worker
      exposure to pesticide residues in wool.

PMID- 11290354
TI  - Data on application frequency of pesticide for risk assessment purposes.
AB  - In risk assessment, information from toxicity studies is combined with
      information on worker exposure. In general, agricultural practice implies long
      term intermittent exposure to various pesticides. This issue can only be
      addressed when sufficient information exist, on exposure regimes. Patterns of
      application of pesticides and the use frequency of single pesticide products on a
      number of representative key crops from various agricultural sectors in the
      Netherlands were studied. The results show that there is an enormous variation in
      pesticide usage between and within sectors. On nearly all crops studied the
      number of applications with insecticides and fungicides was higher than the
      number of applications with herbicides. The average frequency of application of a
      the most used insecticide and fungicide products on the most intensively treated
      crops was between 10 and 20 times a year. But on most crops single pesticide
      products were used not more than seven times a year.

PMID- 11290356
TI  - Crossing the river stone by stone: approaches for residential risk assessment for
      consumers.
AB  - Consumer products may contain constituents that warrant a risk analysis if they
      raise toxicological concern. Risk assessments are performed a priori, e.g. for
      pesticides and biocides, and a posteriori, to diagnose risks of contaminants. An
      overview is presented of residential exposure assessment and risk
      characterization. For exposure assessment, predictive models are used to estimate
      exposure concentrations. The available data on product use are used to quantify
      the intensity of exposure. Often, both exposure concentration and product use
      show high variability. Worst case assessments cope with variability and
      uncertainty in data poor situations by selecting 'worst case' values for
      exposures and exposure factors. Probabilistic models may be used to quantify and
      model variability and uncertainty when appropriate data is available. The Margin
      Of Safety approach to characterize risk is discussed. Many biocides handled by
      consumers are used now and then and (sub)acute exposure and toxicology will be
      most relevant. Users and children are generally seen as critical groups during
      the application and post-application phases of exposure, respectively. Still, the
      diversity of consumer products requires consideration of the merits of each case.
      We conclude that residential risk assessment is still searching for methods, data
      and models. Probabilistic methods appear to be useful tools, but a major
      challenge is to integrate them in regulatory frameworks.

PMID- 11290357
TI  - New challenges: residential pesticide exposure assessment in the California
      Department of Pesticide Regulation, USA.
AB  - Residential exposure assessment is in an early stage of development within many
      of the regulatory agencies responsible for pesticides. Some of the impetus for
      residential assessment comes from the Food Quality Protection Act (FQPA), a
      federal law adopted in 1996 in the USA. The FQPA mandates that the aggregate and
      cumulative risks from all nonoccupational sources of exposure to similarly acting
      pesticides be assessed. The development of methods for residential exposure
      assessment is therefore proceeding in tandem with methods for aggregate risk
      assessment. The California Department of Pesticide Regulation (Cal DPR) regulates
      pesticides in the state of California much as the US EPA does at the national
      level. While Cal DPR is not explicitly bound by the federal law, it recognizes
      the importance of residential exposure and of cumulative risk, and tries to
      harmonize its methods with those of US EPA. Accordingly, Cal DPR is developing
      guidance for residential exposure assessment. Some factors to consider are the
      following: (1) although the end goal may be total exposure from all sources, in
      order to regulate the use of products it is necessary to have separate estimates
      of exposure from individual sources and routes; (2) probabilistic approaches will
      be used increasingly, and they must separate variability and uncertainty; (3)
      there is a critical need for data on residential use of pesticides, including the
      frequency of mishaps and improper handling; (4) data are needed on long-term
      activity patterns of individuals, including residential and occupational history;
      (5) regulatory agencies need a way to identify and screen potential exposure
      scenarios, in order to streamline the risk assessment process.

PMID- 11290358
TI  - Methods to study everyday use of products in households: The Wageningen Mouthing
      Study as an example.
AB  - Several methods exist to study human behaviour in everyday life: e.g. an oral or
      written interview, measurement of physical variables and observation. All of them
      have their advantages and disadvantages, which are described in this paper. When
      a clear picture of actual human behaviour and information about an entire
      activity are required, for example to assess risks of exposure to chemical
      substances, it is best to use a combination of available methods. In this way the
      advantages of all methods can be combined. This was done in the Wageningen
      mouthing study of which some results are presented.

PMID- 11290359
TI  - Assessing aggregate and cumulative pesticide risks using a probabilistic model.
AB  - Determining aggregate and cumulative risks from exposures to pesticides presents
      a number of challenges. The analysis must capture the correlations in residues
      that occur from both additive and exclusionary processes in the use of
      pesticides. The analysis also requires a quantitative mechanism for evaluating
      risks associated with exposures to mixtures of pesticides. This paper presents an
      analysis of aggregate exposures and risks associated with exposures to a
      pesticide, Alpha, and the cumulative exposure to and risk from three pesticides,
      Alpha, Beta, and Gamma. The cumulative risks are evaluated by determining the
      systemic (absorbed) doses that result from inhalation, dermal, and oral exposures
      to the pesticides. A 'relative toxicity' model is used to evaluate cumulative
      risks. The assessment of cumulative exposure was performed using the LifeLine
      Version 1.0. The model simulates pesticide exposure using an individual-based
      approach where daily exposures are evaluated for each person, season, and
      location.

PMID- 11290360
TI  - Biomonitoring of persons exposed to insecticides used in residences.
AB  - Pesticides used indoors inevitably result in some unintentional and unavoidable
      exposures of residents. Measured dosages of residents are well below toxic
      levels. Exposures (microg/kg-day) are substantially less and occur over a longer
      time than suggested by unvalidated estimates derived from previous extreme,
      conservative default assumptions based solely on environmental residues. Human
      chlorpyrifos exposures were monitored following three different types of
      applications: fogger, broadcast, and crack-and-crevice. Persistence of total
      residue on carpet was substantially greater than the persistence of transferable
      residue (microg/cm(2)). Low-level (microg/kg) exposures of family members
      persisted for periods of weeks to a month after pesticide use. Although few
      children who resided with their parents in pest-protected homes have been
      monitored, they eliminated more biomarker than their parents on a kg body weight
      day basis when absorbed dosages (microg/kg-day) were derived from spot urine
      specimens corrected for volume by an age-specific creatinine correction.
      Ultimately environmental residues may become useful elements of predictive
      residential exposure models, but their potential contribution to indirect
      exposure assessments must include careful determination of residue availability
      for contact transfer to clothing or skin and biological validation. When
      environmental data from monitoring studies reported here were used to estimate
      residential exposure according to Residential Exposure Assessment Standard
      Operating Procedures (SAP meeting, 1997), measured exposures were substantially
      less than assessments. Experimental and situational monitoring of exposed persons
      is essential for meaningful and responsible predictive resident exposure model
      building.

PMID- 11290361
TI  - Toxicology studies should be relevant for worker risk assessment--summary of
      discussions.

PMID- 11290362
TI  - Probabilistic exposure assessment is essential for assessing risks--summary of
      discussions.

PMID- 11290363
TI  - Field use information is important for assessing the risk of exposure--summary of
      discussions.

PMID- 11290364
TI  - Residential exposure should be considered in appropriate terms: summary of
      discussions.

PMID- 11290365
TI  - Risk assessment of worker and residential exposure to pesticides: conclusions and
      recommendations.

PMID- 11290367
TI  - Nicorandil--induced ATP release in endothelial cells of rat caudal artery is
      associated with increase in intracellular Ca(2+).
AB  - The effect of nicorandil, an ATP-sensitive K(+) channel opener, on the level of
      intracellular Ca(2+) ([Ca(2+)](i)) and on ATP release in endothelial cells of the
      rat caudal artery was examined using a fluorescent confocal microscopic imaging
      system and high-performance liquid chromatography (HPLC) with fluorescent
      detection, respectively. Nicorandil significantly increased [Ca(2+)](i) and the
      overflow of ATP and its metabolites. The former reaction was abolished in the
      absence of extracellular Ca(2+), but it did not change in the presence of
      thapsigargin or cyclopiazonic acid. The increase in the overflow of ATP and
      [Ca(2+)](i) induced by nicorandil was markedly suppressed by glibenclamide, an
      ATP-sensitive K(+) channel blocker. The increase of [Ca(2+)](i) induced by
      nicorandil was significantly and inversely correlated with the level of
      intracellular ATP in the endothelial cells, suggesting that activation of ATP
      sensitive K(+) channels by nicorandil increases Ca(2+) influx in endothelial
      cells. The increase of [Ca(2+)](i) might be associated with ATP release.

PMID- 11290368
TI  - Pharmacological characterization of interactions of RO 25-6981 with the NR2B
      (epsilon2) subunit.
AB  - We used ligand binding to ascertain whether the pharmacological actions of RO 25
      6981 [(R:(*), S:(*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1
      piperidinepropanol] match those of other NR2B (epsilon2) subunit specific agents.
      RO 25-6981 inhibited binding of 125I-MK801 [iodo-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohept-5,10-imine maleate] to receptors made from NR1a/epsilon2
      but not NR1a/epsilon1. Increasing the concentration of spermidine did not change
      the efficacy of RO 25-6981 and minimally changed the IC(50) value. Chimeric
      epsilon1/epsilon2 receptors demonstrated that the structural determinants for
      high affinity actions of RO 25-6981 were contained completely within the first
      464 amino acids, but no receptor retained wildtype features when the size of the
      epsilon2 component was decreased further. Epsilon1Q336R receptors were more
      inhibited by ifenprodil and RO 25-9681 than wildtype epsilon1 receptors in ligand
      binding assays but not in functional assays. Selected mutations of epsilon2E200
      and epsilon2E201 also decreased the sensitivity of receptors to ifenprodil and RO
      25-6981. These results suggest that RO 25-6981 shares structural determinants
      with ifenprodil and other modulators in the NR2B subunit.

PMID- 11290369
TI  - Molecular cloning and characterization of the mouse P2Y4 nucleotide receptor.
AB  - To isolate the mouse P2Y4 receptor gene, a mouse genomic library was screened
      with a human P2Y4 probe. An open reading frame encoding a protein of 361 amino
      acids was isolated. This protein showed 82% and 95% amino acid identity with the
      human and rat P2Y4 receptors, respectively. By reverse transcription and
      polymerase chain reaction (RT-PCR), the P2Y4 messenger RNA was detected in mouse
      liver, intestine, stomach, bladder and lung among the 16 mouse tissues tested. In
      1321N1 transfected cells, the mouse P2Y4 receptor was equally activated by UTP
      and ATP, and was antagonized by pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic
      acid (PPADS) and Reactive Blue 2, and not by suramin. Moreover, when expressed in
      1321N1 cells, the rat P2Y4 is also antagonized by PPADS. Thus, when compared in
      the same expression system, the mouse P2Y4 is closer to the rat ortholog in terms
      of agonist stimulation, while in terms of antagonist profile, the three P2Y4
      receptor orthologs are similar.

PMID- 11290370
TI  - Effect of beta-estradiol on voltage-gated Ca(2+) channels in rat hippocampal
      neurons: a comparison with dehydroepiandrosterone.
AB  - We investigated the effects of beta-estradiol, dehydroepiandrosterone and
      dehydroepiandrosterone sulfate on intracellular calcium concentration
      ([Ca(2+)](i)) increases induced by gamma-aminobutyric acid (GABA), high K(+) and
      N-methyl-D-aspartate acid (NMDA) in cultured hippocampal neurons. Acute treatment
      with beta-estradiol, dehydroepiandrosterone and dehydroepiandrosterone sulfate
      inhibited the GABA-induced [Ca(2+)](i) increases to the similar extent.
      Tamoxifen, an estrogen receptor antagonist, did not block the inhibitory effects
      of beta-estradiol. On the other hand, GABA type A (GABA(A)) receptor antagonists,
      picrotoxin and bicuculline, blocked the GABA-induced [Ca(2+)](i) increases.
      Previously, we demonstrated that GABA- and high K(+)-induced [Ca(2+)](i)
      increases were commonly mediated by voltage-gated calcium channels (VGCCs).
      Therefore, we examined the effects of these steroids on the high K(+)-induced
      [Ca(2+)](i) increases. The inhibitory effect of beta-estradiol on the high K(+)
      induced [Ca(2+)](i) increases was much greater than that of
      dehydroepiandrosterone and dehydroepiandrosterone sulfate. beta-Estradiol
      inhibited the NMDA-induced [Ca(2+)](i) increases with an IC(50) of 51.8 microM
      and NMDA responses were reduced to half in the presence of 10 micro M nifedipine,
      indicating that the NMDA-induced [Ca(2+)](i) increases also involved VGCCs.
      Further, we examined the inhibitory effect of beta-estradiol on the high K(+)
      induced [Ca(2+)](i) increases in the presence of a N-type VGCCs antagonist, 1
      microM omega-conotoxin, or a L-type VGCCs antagonist, 10 microM nifedipine. The
      IC(50) value of beta-estradiol alone (45.5 microM) was similar to that of omega
      conotoxin (33.1 microM), while the value combined with nifedipine was reduced to
      2.2 microM. beta-Estradiol also abolished the positive modulatory effect of L
      type VGCCs agonist, 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2
      (trifluoromethyl)phenyl]pyridine-3-carboxylic acid methyl ester (Bay K 8644). Our
      results showed that the inhibitory mechanism of beta-estradiol is different from
      that of dehydroepiandrosterone and dehydroepiandrosterone sulfate and beta
      estradiol may act primarily at L-type VGCCs.

PMID- 11290371
TI  - Anti-tumor activities of chondroitinase AC and chondroitinase B: inhibition of
      angiogenesis, proliferation and invasion.
AB  - In the current study, two specific glycosaminoglycan lyases, chondroitinase AC
      and chondroitinase B, were utilized to examine the roles of chondroitin sulfates
      and dermatan sulfate in tumor metastasis and angiogenesis. Melanoma cells (SK
      MEL) or endothelial cells were treated with either medium or chondroitinase
      enzyme. Chondroitinase AC inhibited melanoma invasion and proliferation as well
      as endothelial proliferation and angiogenesis. Apoptosis of melanoma and
      endothelial cells, as measured by the activity of caspase-3, was also increased
      by chondroitinase AC, but not by chondroitinase B. Chondroitinase B inhibited
      endothelial and melanoma proliferation and invasion, but to a lesser extent than
      chondroitinase AC. Neither chondroitinase had a detectable effect on gelatinase
      secretion by melanoma cells. These results indicate that both chondroitin and
      dermatan sulfates regulate many cellular activities related to metastasis.

PMID- 11290372
TI  - Dual effect of cAMP on the writhing response in mice.
AB  - The intraperitoneal injection of agents that increase the intracellular level of
      cyclic AMP (cAMP), reduced significantly the number of writhes induced by acetic
      acid and zymosan in mice. However, dibutyryl cyclic AMP (Db-cAMP) induced a dual
      response: (a) low doses caused antinociception, and (b) a high dose potentiated
      the nociceptive effect of a low concentration of acetic acid. High doses of Db
      cAMP also reversed the antinociceptive effect of dexamethasone and the depletion
      of resident peritoneal cells. We also demonstrated that a low dose of Db-cAMP,
      forskolin or dexamethasone inhibited the production of tumor necrosis factor
      alpha and interleukin-1 beta by macrophages stimulated by zymosan. In conclusion,
      this study suggests that cAMP has a dual effect in the writhing model: an
      antinociceptive effect due to its modulatory action on resident peritoneal cells,
      thus, reducing the synthesis of mediators involved in the nociceptive response,
      and a nociceptive effect by directly sensitizing the nociceptive neuron.

PMID- 11290373
TI  - Effect of 8-iso-prostaglandin F(2 alpha) on acetylcholine release from
      parasympathetic nerves in guinea pig airways.
AB  - 8-Iso-prostaglandin F(2 alpha) is present in increased amounts in airway
      inflammation. 8-Iso-prostaglandin F(2 alpha) constricts the airways via the
      activation of thromboxane A(2) receptors. However, thromboxane A(2) receptors are
      also present pre-junctionally on cholinergic nerve terminals innervating guinea
      pig trachea. We have demonstrated that 8-iso-prostaglandin F(2 alpha) inhibited
      electrical field stimulation-evoked [3H]acetylcholine release in a concentration
      dependent manner, an effect that was not inhibited by the selective thromboxane
      A(2) receptor antagonist 4(Z)-6-[(2,4,5 cis)2-(2-chlorophenyl)-4-(2
      hydroxyphenyl)1,3-dioxan-5-yl]hexenoic acid (ICI 192,605). These data suggest
      that 8-iso-prostaglandin F(2 alpha) inhibits acetylcholine release through a
      receptor distinct from the thromboxane A(2) receptor and provides evidence that
      isoprostanes may have a 'dual' role as both beneficial and deleterious mediators
      in airway disease.

PMID- 11290375
TI  - Tetrahydrobiopterin improves endothelium-dependent vasodilation in nitroglycerin
      tolerant rats.
AB  - Tolerance to nitroglycerin is caused by a nitroglycerin-mediated increase in
      vascular superoxide anion production. Administration of tetrahydrobiopterin (co
      factor for endogenous nitric oxide (NO) formation) may potentially influence
      nitroglycerin tolerance in at least two different ways. Firstly,
      tetrahydrobiopterin may act as a scavenger of the nitroglycerin-mediated
      production of superoxide anions. Secondly, tetrahydrobiopterin may protect
      endothelial NO synthesis from the deleterious effects of increased oxidative
      stress. This study investigates whether in vivo nitroglycerin tolerance is
      affected by tetrahydrobiopterin supplementation and assesses the in vivo role of
      tetrahydrobiopterin in endogenous NO-mediated vasodilation in normal and
      nitroglycerin-tolerant rats. The results show that tetrahydrobiopterin does not
      affect nitroglycerin-derived, NO-mediated vasodilation, but reduces baseline mean
      arterial blood pressure (by 8 mm Hg, P<0.05) and normalizes endothelium-dependent
      responses to N(G)-monomethyl-L-arginine (L-NMMA) (from 7+/-1 to 22+/-4 mm Hg,
      P<0.05) in nitroglycerin-tolerant rats. It is concluded that altered
      bioavailability of tetrahydrobiopterin is involved in the pathophysiology of
      endothelial dysfunction seen in nitroglycerin tolerance.

PMID- 11290374
TI  - The allosteric interaction of otenzepad (AF-DX 116) at muscarinic M2 receptors in
      guinea pig atria.
AB  - The effects of the muscarinic receptor antagonist, otenzepad, in combination with
      the competitive antagonists N-methylscopolamine, dexetimide and atropine, or the
      allosteric modulators, C(7)/3'-phth, gallamine and alcuronium, were measured in
      the guinea pig electrically driven left atrium using the agonists, carbachol or
      acetylcholine. Otenzepad, in combination with C(7)/3'-phth or gallamine, gave
      concentration-ratios close to additive and in agreement with theoretical model
      predictions for combination of two allosteric modulators acting at a common site.
      However, when otenzepad was combined with alcuronium, dexetimide or N
      methylscopolamine, supra-additive effects were observed. For either competitive
      antagonist in combination with otenzepad, the degree of supra-additivity was more
      evident after 2-h equilibration than after 40 min. When otenzepad was combined
      with atropine, no supra-additivity was observed with carbachol as the agonist,
      but was evident with acetylcholine. Otenzepad was also unable to fully inhibit
      [3H]N-methylscopolamine binding when the radioligand was employed at a
      concentration of approximately 100 x K(D). It is concluded that the action of
      otenzepad involves an allosteric site and a number of possibilities are discussed
      for its location.

PMID- 11290376
TI  - Involvement of melatonin MT(3) receptors in the regulation of intraocular
      pressure in rabbits.
AB  - Melatonin, a neurohormone secreted by the pineal gland, can stimulate three
      subtypes of receptors, namely: mt(1), MT(2) and MT(3). We examined the ability of
      melatonin and the selective MT(3) receptor agonist, 5-methoxycarbonylamino-N
      acetyltryptamine (5-MCA-NAT), to modify intraocular pressure in rabbits. Both
      compounds significantly reduced intraocular pressure, maximally by 24% and 43%,
      respectively, with IC(50) values of 363+/-23.0 and 423+/-30.0 ng/10 microl (1.6+/
      0.1 and 1.8+/-0.1 nmol, respectively). The non-specific melatonin receptor
      antagonist, luzindole, abolished the depressant effect of both compounds, thus
      confirming the involvement of melatonin receptors. Our results show, for the
      first time, a functional response that may be regulated by melatonin MT(3)
      receptors, and provide evidence that supports a role of melatonin in the
      circadian changes of intraocular pressure.

PMID- 11290378
TI  - 14th International Conference on Antiviral Research. Seattle, Washington, April 8
      12, 2001. Program and abstracts.

PMID- 11290377
TI  - Isolated rat stomach ECL cells generate prostaglandin E(2) in response to
      interleukin-1 beta, tumor necrosis factor-alpha and bradykinin.
AB  - The ECL cells control parietal cells by releasing histamine in their immediate
      vicinity. Gastrin and pituitary adenylate cyclase-activating peptide (PACAP)
      stimulate histamine secretion from isolated ECL cells, while somatostatin and
      galanin inhibit stimulated secretion. Prostaglandin E2 and related prostaglandins
      likewise suppress ECL-cell histamine secretion. Conceivably, that is how they
      inhibit acid secretion. In the present study, we examined if prostaglandin E2 can
      be generated by isolated ECL cells. Rat stomach ECL cells were purified (>90%
      purity) by counterflow elutriation and gradient centrifugation and cultured for
      48 h. ECL cell stimulants (gastrin and PACAP) and inflammatory agents
      (interleukin-1 beta, tumor necrosis factor-alpha and bradykinin) were tested for
      their ability to induce prostaglandin E2 accumulation (24-h incubation), measured
      by radioimmunoassay. Gastrin and PACAP did not affect prostaglandin E2
      accumulation but interleukin-1 beta (300 pg/ml), tumor necrosis factor-alpha (10
      ng/ml) and bradykinin (1 microM) induced a 2- to 3-fold increase in the amount of
      prostaglandin E2 accumulated. While the combination of interleukin-1 beta and
      bradykinin induced a 9-fold increase, the combination interleukin-1 beta+tumor
      necrosis factor-alpha and bradykinin + tumor necrosis factor-alpha induced
      additive effects only. The combination of interleukin-1 beta + tumor necrosis
      factor-alpha + bradykinin did not induce a greater effect than interleukin-1 beta
      + bradykinin. The effect of interleukin-1 beta + bradykinin was abolished by
      adding 10 nM hydrocortisone (suppressing phospholipase A2 and cyclooxygenase) or
      1 microM indomethacin (inhibiting cyclooxygenase). Incubating ECL cells in the
      presence of interleukin-1 beta+bradykinin for 24 h reduced their ability to
      secrete histamine in response to gastrin. The inhibitory effect was reversed by 1
      microM indomethacin. Also, increasing the concentrations of hydrocortisone in the
      medium resulted in an enhanced gastrin-stimulated histamine secretion. Hence, the
      previously described acid-inhibiting effect of inflammatory agents may be
      explained by inhibition of ECL-cell histamine mobilization, consequent to
      enhanced formation of prostaglandin E2 by cells in the oxyntic mucosa, including
      the ECL cells themselves.

PMID- 11290379
TI  - 8-OH-DPAT and MK-801 affect epileptic activity independently of vigilance.
AB  - Vigilance and parallel occurrence of epileptic activity after administration of
      the 5-HT(1A) agonist 8-OH-DPAT and the NMDA receptor antagonist MK-801 were
      studied in the genetic absence epilepsy model WAG/Rij rats. Spike-wave discharges
      (SWD) were present predominantly in passive awake and light slow wave sleep
      (SWS1) either in control animals or after treatments. Injection of 8-OH-DPAT
      (20.0 microg/rat i.c.v.) caused marked increase and MK-801 (10.0 microg/rat
      i.c.v.) decrease in SWD densities, thus the ratios of SWD in passive awake and in
      SWS1. SWD densities of MK-801 plus 8-OH-DPAT in combination were similar to those
      of CSF+CSF treated control rats. Both 8-OH-DPAT and MK-801 transiently increased
      the duration of active awake, increased latency and decreased duration of rapid
      eye movement (REM) sleep. 8-OH-DPAT increased the amount of SWD despite the
      decrease in the duration of SWS1. MK-801 decreased the amount of SWD despite the
      lack of significant change in duration of passive awake or SWS1. Pre-treatment
      with MK-801 reversed 8-OH-DPAT- induced increase in duration of SWD without any
      effect on 8-OH-DPAT-induced changes in sleep parameters. Our studies provide
      evidence that 8-OH-DPAT-induced epileptic activity is independent of its effect
      on sleep, and that interaction of serotonergic and glutamatergic systems plays a
      role in the generation of SWD, but not in the regulation of vigilance and sleep.

PMID- 11290380
TI  - An in vitro model for the study of microglia-induced neurodegeneration:
      involvement of nitric oxide and tumor necrosis factor-alpha.
AB  - The precise function of activated microglia and their secretory products remains
      controversial. In order to assess the role of microglial secretion products, we
      established an in vitro model of an inflammatory reaction in the brain by co
      culturing microglial and neuronal cell lines. Upon stimulation with interferon
      gamma and lipopolysaccharides, the microglial cells adopted an activated
      phenotype and secreted tumor necrosis factor-alpha (TNF-alpha), prostaglandin
      E(2) and nitric oxide (NO). Neuronal degeneration was quantified by measuring the
      concentrations of microtubule associated protein tau and neuron specific enolase,
      which are also used as diagnostic tool in Alzheimer's disease, in supernatants.
      In activated contact co-cultures, the levels of these neuronal markers were
      significantly raised compared to non-activated co-cultures. NO-synthase
      inhibitors significantly diminished the rise of tau in activated co-cultures,
      while indomethacin, superoxide dismutase, or a neutralizing TNF-alpha antibody
      did not. When a chemical NO-donor or TNF-alpha were added to pure neuronal
      cultures, cell viability was significantly reduced. TNF-alpha increased neuronal
      sensitivity towards NO. There were indications that a part of the cells died by
      apoptosis. This model demonstrates a neurotoxic role for NO in microglia-induced
      neurodegeneration and provides a valuable in vitro tool for the study of
      microglia-neuron interactions during inflammation in the brain.

PMID- 11290381
TI  - Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on
      dopamine secretion in PC12 rat pheochromocytoma cells.
AB  - Naturally occurring neurotoxins, 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines
      (DHTIQs), thought to be the causative agents of Parkinsonism. DHTIQs including
      norsalsolinol have been found in the mammalian central nervous system.
      Norsalsolinol can be formed by a non-enzymatic Pictet-Spengler condensation
      reaction between dopamine and formaldehyde, and has been detected in the urine of
      Parkinsonian patients. However, the effects of DHTIQs on the secretion of
      dopamine, as well as other neurotransmitters, are not well understood. This study
      investigated the effects of norsalsolinol on dopamine secretion from nerve growth
      factor-differentiated PC12 cells. Norsalsolinol (1-100 microM) pretreatment
      suppressed both ATP (100 microM)- and K(+) (50 mM)-induced dopamine secretion
      from PC12 cells in a concentration-dependent fashion, but did not affect basal
      dopamine secretion. In beta-escin-permeabilized PC12 cells, norsalsolinol
      pretreatment suppressed Ca(2+) (pCa=4-8)-induced dopamine secretion, but did not
      inhibit the secretagogue-induced change in intracellular Ca(2+) concentration.
      These results suggest that norsalsolinol causes the inhibition of secretagogue
      induced dopamine secretion from PC12 cells without altering intracellular Ca(2+)
      concentration. Inhibition of dopamine secretion by norsalsolinol may also be
      involved in postural abnormality in Parkinson's disease.

PMID- 11290382
TI  - Cortical 5-HT(1A) receptor downregulation by antidepressants in rat brain.
AB  - Total 5-HT binding sites and 5-HT(1A) receptor density was measured in brain
      regions of rats treated with imipramine (5 mg/kg body wt), desipramine (10 mg/kg
      body wt) and clomipramine (10 mg/kg body wt), for 40 days, using [3H]5-HT and
      [3H]8-OH-DPAT, respectively. It was observed that chronic exposure to tricyclic
      antidepressants (TCAs) results in significant downregulation of total [3H]5-HT
      binding sites in cortex (42-76%) and hippocampus (35-67%). The 5-HT(1A) receptor
      density was, however, decreased significantly (32-60%) only in cortex with all
      the three drugs. Interestingly, in hippocampus imipramine treatment increased the
      5-HT(1A) receptor density (14%). The affinity of [3H]8-OH-DPAT was increased only
      with imipramine treatment both in cortex and hippocampus. The affinity of [3H]5
      HT to 5-HT binding sites in cortex was increased with imipramine treatment and
      decreased with desipramine and clomipramine treatment. 5-HT sensitive adenylyl
      cyclase (AC) activity was significantly increased in cortex with imipramine (72%)
      and clomipramine (17%) treatment, whereas in hippocampus only imipramine
      treatment significantly increased AC activity (50%). In conclusion, chronic
      treatment with TCAs results in downregulation of cortical 5-HT(1A) receptors
      along with concomitant increase in 5-HT stimulated AC activity suggesting the
      involvement of cortical 5-HT(1A) receptors in the mechanism of action of TCAs.

PMID- 11290383
TI  - Molecular determinants of desensitization and assembly of the chimeric GABA(A)
      receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2
      and gamma2.
AB  - Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order
      to elucidate the structural requirements for GABA(A) receptor desensitization and
      assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing
      the extracellular N-terminal domain of alpha1 or gamma2 and the remainder of the
      gamma2 or alpha1 subunits, respectively, were expressed with beta2 and
      beta2gamma2 in Spodoptera frugiperda (Sf-9) cells using the baculovirus
      expression system. The (alpha1/gamma2)beta2 and (alpha1/gamma2)beta2gamma2 but
      not the (gamma2/alpha1)beta2 and (gamma2/alpha1)beta2gamma2 subunit combinations
      formed functional receptor complexes as shown by whole-cell patch-clamp
      recordings and [3H]muscimol and [3H]flunitrazepam binding. Moreover, the surface
      immunofluorescence staining of Sf-9 cells expressing the (alpha1/gamma2)
      containing receptors was pronounced, as opposed to the staining of the
      (gamma2/alpha1)-containing receptors, which was only slightly higher than
      background. To explain this, the (alpha1/gamma2) and (gamma2/alpha1) chimeras may
      act like alpha1 and gamma2 subunits, respectively, indicating that the
      extracellular N-terminal segment is important for assembly. However, the
      (alpha1/gamma2) chimeric subunit had characteristics different from the alpha1
      subunit, since the (alpha1/gamma2) chimera gave rise to no desensitization after
      GABA stimulation in whole-cell patch-clamp recordings, which was independent of
      whether the chimera was expressed in combination with beta2 or beta2gamma2.
      Surprisingly, the (alpha1/gamma2)(gamma2/alpha1)beta2 subunit combination did
      desensitize, indicating that the C-terminal segment of the alpha1 subunit may be
      important for desensitization. Moreover, desensitization was observed for the
      (alpha1/gamma2)beta2gamma2 receptor with respect to the direct activation by
      pentobarbital. This suggests differences in the mechanism of channel activation
      for pentobarbital and GABA.

PMID- 11290384
TI  - Amyloid beta protein activates PKC-delta and induces translocation of
      myristoylated alanine-rich C kinase substrate (MARCKS) in microglia.
AB  - The increased accumulation of activated microglia containing amyloid beta protein
      (Abeta) around senile plaques is a common pathological feature in subjects with
      Alzheimer's disease (AD). Much less is known, however, of intracellular signal
      transduction pathways for microglial activation in response to Abeta. We
      investigated intracellular signaling in response to Abeta stimulation in primary
      cultured rat microglia. We found that the kinase activity of PKC-delta but not
      that of PKC-alpha or -epsilon is increased by stimulation of microglia with
      Abeta, with a striking tyrosine phosphorylation of PKC-delta. In microglia
      stimulated with Abeta, tyrosine phosphorylation of PKC-delta was evident at the
      membrane fraction without an overt translocation of PKC-delta. PKC-delta co
      immunoprecipitated with MARCKS from microglia stimulated with Abeta. Abeta
      induced translocation of MARCKS from the membrane fraction to the cytosolic
      fraction. Immunocytochemical analysis revealed that phosphorylated MARCKS
      accumulated in the cytoplasm, particularly at the perinuclear region in microglia
      treated with Abeta. Taken together with our previous observations that Abeta
      induced phosphorylation of MARCKS and chemotaxis of microglia are inhibited by
      either tyrosine kinase or PKC inhibitors, our results provide evidence that Abeta
      induces phosphorylation and translocation of MARCKS through the tyrosine kinase
      PKC-delta signaling pathway in microglia.

PMID- 11290385
TI  - Modular structure of cAMP response element binding protein 2 (CREB2).
AB  - The transcription factor cAMP-response element binding protein 2 (CREB2), a
      member of the family of basic region leucine zipper proteins, has been suggested
      to function in the brain as a repressor of long-term memory. Using recombinant
      proteins we show that CREB2 binds in vitro to the palindromic cAMP response
      element derived from the secretogranin II gene. Recent studies of the
      chromogranin B, secretogranin II and enkephalin genes showed that CREB2
      functioned as a repressor of cAMP-induced transcription. We analyzed the ability
      of CREB2 to repress transcription using model promoters. A molecular dissection
      of the CREB2 molecule revealed that CREB2 lacks a transferable repressor domain
      suggesting that CREB2 may function solely as a "passive" transcriptional
      repressor. In contrast, "active" repressor domains derived from the thyroid
      hormone receptor alpha or the NK10 zinc finger protein containing a "Kruppel
      associated box" could be transfered to a heterologous DNA-binding domain and
      functioned as fusion proteins in repressing transcription of a reporter gene. In
      addition, a strong activation domain located at the N-terminus was identified in
      the CREB2 protein suggesting that CREB2 may act as an activator of transcription
      by binding to different genetic regulatory elements.

PMID- 11290386
TI  - The alteration of gamma-aminobutyric acid-transaminase expression in the gerbil
      hippocampus induced by seizure.
AB  - It is well established that GABA degradation may play a key role in
      epileptogenesis. However, whether or not the expression of GABA-transaminase
      (GABA-T), which catalyzes GABA degradation and participates in the neuronal
      metabolism via GABA shunt, changes chronologically after on-set of seizure
      remains to be clarified. To identify the change of GABA-T expression in seizure,
      GABA-T expression in the gerbil hippocampus, associated with different sequelae
      of spontaneous seizures, was investigated. The distribution pattern of GABA-T
      immunoreactive neurons in the hippocampus between the seizure-resistant and pre
      seizure group of seizure sensitive gerbils was similar. Interestingly, at 30 min
      postictal, the enhancement of GABA-T immunoreactivity in the perikarya was
      apparently observed. This contrasted with the decline in GABA-T immunoreactivity
      in the granular and pyramidal layer. At 12-24 h postictal, GABA-T
      immunoreactivity in the hilar neurons had declined significantly. However, the
      GABA-T immunoreactivity in the granular layer increased. These findings suggest
      that in the gerbil, the alteration in GABA-T expressions may play an important
      role in the self-recovery mechanism from seizure attack via both GABA degradation
      and regulation of neuronal metabolism.

PMID- 11290387
TI  - Effects of apolipoprotein E (apoE) isoforms, beta-amyloid (Abeta) and apoE/Abeta
      complexes on protein kinase C-alpha (PKC-alpha) translocation and amyloid
      precursor protein (APP) processing in human SH-SY5Y neuroblastoma cells and
      fibroblasts.
AB  - We investigated the effects of different apolipoprotein E (apoE) isoforms, Abeta
      (1-42), and apoE/Abeta complexes on PKC-alpha translocation and APP processing in
      human SH-SY5Y neuroblastoma cells and fibroblasts. Treatment of cells with either
      10 nM apoE3 or apoE4, 10 microM Abeta (1-42), or apoE/Abeta complexes induced
      significant translocation of PKC-alpha in both cell types. Effects were seen
      using both human recombinant apoE and apoE loaded into beta-very low density
      lipoprotein (beta-VLDL) particles. Time course (5-24 h) studies of APP processing
      revealed that some conditions induced transient or moderate increases in the
      secretion of proteins detected by 22C11. In contrast, the secretion of alpha
      secretase cleaved APP was either not modified or transiently decreased, as
      determined by immunoblotting with the antibody 6E10. These results suggest that
      apoE, Abeta (1-42) and apoE/Abeta complexes can modulate PKC activity but do not
      have major consequences for APP processing. These effects could contribute to the
      reported PKC alterations seen in AD. However, it is unlikely that the
      contribution of different apoE isoforms to AD pathology occurs via effects on APP
      processing.

PMID- 11290388
TI  - L-Deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP(+)
      and beta-carbolinium: a microdialysis study in rats.
AB  - N-Methyl-4-phenylpyridinium (MPP(+)) and 2,9-di-methyl-norharmanium (2,9
      Me2NH(+)), which is a beta-carbolinium proposed as an endogenous MPP(+)-like
      toxin underlying Parkinson's disease, are strong mitochondrial toxins. We have
      measured the extracellular lactate levels as a marker for the in vivo cell
      hypoxia in the striatum of freely moving rats. The perfusions with MPP(+) and 2,9
      Me2NH(+) increased extracellular lactate levels in a dose-dependent manner. These
      increases in lactate levels were significantly prevented by the co-perfusion with
      10 microM L-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, but not by
      pargyline, a non-specific MAO inhibitor. The increase in extracellular lactate
      levels was considered to be the reflection of the cell damage resulted from the
      impairment of mitochondrial function. The present results suggested that L
      deprenyl would rescue nerve cells from these toxins through the direct influence
      on the mitochondrial electron transport.

PMID- 11290389
TI  - Alpha-1 antichymotrypsin and alpha-2 macroglobulin gene polymorphisms are not
      associated with Korean late-onset Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a multifactorial disorder with possible involvement
      of several genetic and environmental factors. For late-onset AD (LOAD), the
      epsilon4 allele of apolipoprotein E (APOE) has been identified as a major
      susceptible gene. However, the observation that APOE epsilon4 accounted for
      approximately one half of the genetic variance of LOAD prompted many researchers
      to undertake genome surveys to identify other susceptible genes. Recently,
      several candidate genes such as alpha-1 antichymotrypsin (ACT) and alpha-2
      macroglobulin (A2M) were reported to be associated with LOAD. To evaluate the
      possible association between these genes and LOAD in Korean population, we
      genotyped ACT A/T and A2M 5-bp deletion (exon 18) polymorphisms in 89 LOAD cases
      and 50 age-matched healthy controls. The frequencies of ACT A and A2M 5-bp
      deletion alleles in LOAD and controls were 0.39 vs. 0.37, and 0.05 vs. 0.05,
      respectively. Although APOE epsilon4 clearly showed higher frequency in LOAD
      (0.34) than that in controls (0.09), giving an odds ratio of 5.14 (95% confidence
      interval, 2.31-11.76), neither ACT nor A2M showed statistically significant
      difference between LOAD and controls regardless of APOE carrier status. Our
      results do not support previously reported association of ACT and A2M with LOAD,
      at least in Korean population.

PMID- 11290390
TI  - Fibrillary beta-amyloid deposits are closely associated with atrophic nitric
      oxide synthase (NOS)-expressing neurons but do not upregulate the inducible NOS
      in transgenic Tg2576 mouse brain with Alzheimer pathology.
AB  - Transgenic mice (Tg2576) that express the Swedish double mutation of human
      amyloid precursor protein and develop Alzheimer-like beta-amyloid deposits in the
      aged brain, were used to study the effect of beta-amyloid deposition on
      expression of both neuronal (nNOS) and inducible nitric oxide synthase (iNOS) in
      cells surrounding beta-amyloid plaques. Nicotinamide adenine dinucleotide
      phosphate-diaphorase histochemistry and double immunofluorescent labeling
      revealed that most of the fibrillary, thioflavine-S-positive cortical beta
      amyloid deposits in 13-, 17-, and 21-month-old transgenic animals were closely
      associated with dystrophic nNOS-positive neurons, while nNOS-bearing neurons
      located more distal to plaques appeared to be unaffected. There was no
      significant expression of iNOS in transgenic mouse brain. The data suggest
      enhanced vulnerability of nNOS-containing neocortical neurons to beta-amyloid
      toxicity. Alternatively, expression of nNOS may also be a response to plaque
      mediated damage of neurons, consistent with a neuroprotective role of nitric
      oxide.

PMID- 11290391
TI  - Functional neuroimaging of cerebellar activation during single word reading and
      verb generation in stuttering and nonstuttering adults.
AB  - Articulatory discoordinations typically observed in fluent and disfluent speech
      of stuttering adults suggest an underlying deficiency in the precise timing
      needed for speech production. Positron emission tomography scans of stuttering
      adults showed generally higher cerebellar activations pre-treatment compared to
      nonstuttering control subjects. Intensive fluency treatment resulted in increased
      cerebellar activation during reading immediately post-treatment and a decrease to
      near normal levels at the 1 year follow scan. In contrast, verb generation
      resulted in a gradual but consistent decrease over the three scans. The results
      suggest that automaticity in motor and cognitive processes during speech
      production may need to be considered as an important factor in future
      investigations of stuttering.

PMID- 11290392
TI  - Effects of acute and repeated restraint stress on corticotropin-releasing hormone
      binding protein mRNA in rat amygdala and dorsal hippocampus.
AB  - Corticotropin-releasing hormone (CRH) mediates endocrine, behavioral, and
      autonomic responses to stress. In addition to binding to two receptor subtypes,
      CRH binds to a CRH-binding protein (CRH-BP). While CRH-BP is hypothesized to play
      a role in regulating levels of free CRH and modulating the stress response, the
      effects of stressors on brain CRH-BP are relatively unexplored. The present study
      determined effects of acute and repeated restraint on CRH-BP mRNA in basolateral
      amygdala (BLA) and dorsal hippocampus (DH), brain regions involved in fear and
      motivation. Using in situ hybridization, we found that a single acute period of
      restraint significantly increased CRH-BP mRNA in BLA by 20% but had no effect in
      DH. Repeated restraint had no effect on basal levels of CRH-BP mRNA in BLA or DH.
      Importantly, repeated restraint blocked the effects of acute restraint in the
      BLA. These results demonstrate differential effects of acute and repeated
      restraint on CRH-BP mRNA.

PMID- 11290393
TI  - Time course of H-reflex conditioning in the rat.
AB  - This study sought to define the course of operantly conditioned change in the rat
      soleus H-reflex and to determine whether, like H-reflex conditioning and spinal
      stretch reflex conditioning in the monkey, it develops in distinct phases. Data
      from 33 rats in which the right soleus H-reflex was trained up (i.e. HRup mode)
      and 38 in which it was trained down (i.e. HRdown mode) were averaged to define
      the courses of H-reflex increase and decrease. In HRup rats, the H-reflex showed
      a large phase I increase within the first 2 days followed by gradual phase II
      increase that continued for weeks. In HRdown rats, the H-reflex appeared to show
      a small phase I decrease and then showed a gradual phase II decrease over weeks.
      In combination with other recent work, the data suggest that H-reflex
      conditioning begins with a rapid mode-appropriate alteration in corticospinal
      tract influence over the spinal arc of the H-reflex, which causes phase I change,
      and that the continuation of this altered influence induces gradual spinal cord
      plasticity that is responsible for phase II change. The results further establish
      the similarity of H-reflex conditioning in primates and rats. Thus, they
      encourage efforts to produce a single coherent model of the phenomenon based on
      data from the two species and indicate the potential clinical relevance of the
      rat data.

PMID- 11290394
TI  - Mouse nestin protein localizes in growth cones of P19 neurons and cerebellar
      granule cells.
AB  - The neuronal growth cone, a highly motile structure at the distal tip of growing
      axons, contains filamentous actin and microtubules as its main cytoskeletal
      components. Using immunocytochemistry, we observed that nestin, which is the
      predominant intermediate filament protein in neuroepithelial cells and young
      neurons of the developing brain, appears to be strongly expressed in neurites and
      growth cones of neurons differentiating from P19 embryonic carcinoma cells in
      vitro. Double-staining of nestin and microtubule-associated protein-2 as well as
      nestin and growth-associated protein-43 revealed that nestin protein localizes in
      neurites and the central regions of growth cones of primary cultures of
      cerebellar granule cells from postnatal day 6 mice. These results suggest a role
      for nestin in growth cone guidance during axon elongation.

PMID- 11290395
TI  - Enhanced expression of L-type Ca2+ channels in reactive astrocytes after ischemic
      injury in rats.
AB  - In the present study, we have examined the expression of voltage-gated calcium
      channels in a rat model of transient focal ischemia using immunohistochemistry.
      Increased expression of class C L-type Ca2+ channels was clearly detected in
      reactive astrocytes in each region of the hippocampus 7 days after ischemic
      injury. On the contrary, class D L-type Ca2+ channels were not expressed in
      reactive astrocytes under these conditions. These patterns were also observed in
      reactive astrocytes in the affected cerebral cortex and fiber tracts. Our study
      showed the spatial and temporal localization of class C L-type Ca2+ channels in
      reactive astrocytes in ischemic rat brain, for the first time. The present
      studies may provide useful data for future investigations to understand the role
      of Ca2+ channels in reactive astrocytes following ischemia or glutamate toxicity.

PMID- 11290396
TI  - Beta-amyloid peptides inhibit acetylcholine release from cholinergic presynaptic
      nerve endings isolated from an electric ray.
AB  - We investigated the effects of beta-amyloid (Abeta) peptides on cholinergic
      synaptosomes isolated from the electric organ of the Japanese marine ray Narke
      japonica. Fresh and pre-incubated solutions of Abeta(1-42) inhibited
      acetylcholine (ACh) release from the synaptosomes evoked by high [K+]
      depolarization when incubated with synaptosomes for 10 min before the
      depolarizing stimulus. A freshly prepared solution of Abeta(1-40) did not inhibit
      the evoked ACh release, but prolonged pre-incubation of Abeta(1-40) solution
      caused the inhibition. Abeta(1-15) neither in fresh nor pre-incubated solution
      inhibited. These results have demonstrated that Abeta peptides can acutely
      inhibit the depolarization-evoked release of ACh by acting directly on
      cholinergic presynaptic nerve endings. The electrophoresis analysis showed a
      strong correlation between Abeta aggregation and its inhibition for ACh release.

PMID- 11290397
TI  - Developmental changes in Cl(-)-ATPase activity in rat brains.
AB  - Developmental changes in brain Cl(-)-ATPase activity were examined using fetal,
      neonatal and adult rats. The Cl(-)-ATPase activity rapidly increased over 20
      postnatal days to a level four-fold higher than that in an 18-day-old fetus. On
      Western blot analysis using an anti-Cl(-)-ATPase/pump 51 kDa subunit (ClP51)
      antibody, the amount of ClP51 protein increased in parallel with Cl(-)-ATPase
      activity. Immunohistochemistry using the same antibody showed Cl(-)-ATPase-like
      immunoreactivity on the cell membranes of neurons such as cerebral and
      hippocampal pyramidal cells and cerebellar Purkinje cells, where the
      immunoreactivity increased with developmental changes in the size and shape of
      the neurons. These findings suggest that neuronal Cl(-)-ATPase activity markedly
      increases during early postnatal development with an increase in the amount of
      Cl(-)-ATPase protein, which may support the formation of inwardly directed
      neuronal Cl(-) gradients.

PMID- 11290398
TI  - Intrastriatal targets of projection fibers from the central lateral nucleus of
      the rat thalamus.
AB  - We examined light and electron microscopically intrastriatal targets of
      projection fibers from the central lateral thalamic nucleus (CL), which is a
      major relay of cerebello-striatal projections. The study was done in the rat by
      combining the anterograde tract-tracing with immunohistochemistry for parvalbumin
      (PV); an anterograde tracer (biotin dextran amine: BDA) was injected into the CL.
      In the striatum, 91% of BDA-labeled axon terminals made asymmetrical synapses on
      PV immunonegative dendritic spines (assumed to be those of striatal projection
      neurons); only 0.5% of BDA-labeled axon terminals made synapses on PV
      immunopositive dendritic shafts. The remaining BDA-labeled axon terminals were in
      synaptic contact with PV immunonegative dendritic shafts. The results suggest
      that the cerebello-striatal projections through the CL predominantly access to
      striatal projection neurons, with only minor access to PV immunopositive (assumed
      to be GABAergic) interneurons in the striatum.

PMID- 11290399
TI  - Increases in cell proliferation and apoptosis in dentate gyrus of anorexia
      (anx/anx) mice.
AB  - The homozygous anorexia mutant (anx/anx) mice present with premature death during
      the third or fourth postnatal week: this phenotype is caused by a lethal
      mutation, anx, on chromosome 2, which has an autosomal recessive mode of
      inheritance. These animals also present phenotypically with decreased food
      intake, weight loss, and neurological deficits such as hyperactivity, body
      tremors, uncoordinated gait, and head weaving. In order to investigate changes in
      the occurrence of cell proliferation and apoptosis in the dentate gyrus of the
      hippocampus of anx/anx mice, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry
      and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)
      assay were performed in this study. In addition, the volume of the dentate gyrus
      was estimated via stereological analysis. anx/anx mice showed significantly
      higher numbers of both BrdU- and TUNEL-positive cells in the dentate gyrus than
      those of the control mice. Furthermore, the volume of the dentate gyrus of
      anx/anx mice was significantly reduced compared to that of the control mice.

PMID- 11290400
TI  - Upregulation of death pathway molecules in rat cerebellar granule neurons
      undergoing apoptosis.
AB  - Cerebellar granule neurons can be maintained in culture in a medium containing
      high serum and depolarising levels of KCl. When serum is removed and the KCl
      levels lowered from 25 to 5 mM, the cells undergo apoptosis. Apoptosis can be
      prevented by inhibitors of transcription or translation, suggesting a need for
      macromolecular synthesis in the apoptotic process. Using quantitative reverse
      transcription-polymerase chain reaction the levels of mRNA for a range of genes
      postulated to be important in apoptosis have been examined. Elevated levels of
      caspase 3, c-Jun, and Fas ligand were found, in addition to a corresponding
      increase in c-Jun protein and activation of caspase-3. These results suggest that
      cerebellar granule neurons upregulate components of both death receptor-mediated
      and the mitochondrial-mediated death pathways.

PMID- 11290401
TI  - Glycogen synthase kinase-3beta immunoreactivity is reduced in the prefrontal
      cortex in schizophrenia.
AB  - Cytoarchitectural abnormalities have been reported in the cortex in
      schizophrenia. These suggest a developmental origin for this disorder. The Wnt
      signalling pathway is involved in the regulation of brain development; disruption
      of this pathway may lead to abnormal cortical development. In this study levels
      of three components of the Wnt signalling pathway; glycogen synthase kinase
      3beta(GSK-3beta), beta-catenin and dishevelled-2 (Dvl-2) were determined in the
      prefrontal cortex of ten schizophrenic and ten control individuals using
      immunoblotting. GSK-3beta levels were significantly reduced in the schizophrenic
      group, while levels of beta-catenin and Dvl-2 did not differ between groups. This
      provides further evidence for an abnormality of the Wnt signalling pathway in
      schizophrenia.

PMID- 11290403
TI  - Partial aortic ligature induces selective long-term c-fos like immunoreactivity
      in the organum vasculosum of the lamina terminalis, medial preoptic area and
      choroid plexus in the rat.
AB  - Partial aortic ligature causes an increase in water and sodium intake.
      Circumventricular brain regions are known to be involved in the regulation of
      these processes. In this work we use c-fos-like immunoreactivity to detect active
      areas involved in the long-term control of increased water and sodium intake due
      to partial aortic ligature. A significant increase in water intake was found on
      the first day after the induction, while natriophilia was observed on the fourth
      day. c-fos-like immunoreactivity was found selectively in the subfornical organ,
      the organum vasculosum of the lamina terminalis, the medial preoptic area, and
      the choroid plexus of the third ventricle. Present results provide further
      evidence for the involvement of circumventricular organs and the preoptic area in
      the regulation of hydromineral balance. Moreover, they suggest a maintained and
      long-term regulation of sodium intake by these same brain areas.

PMID- 11290402
TI  - Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischemia
      in the rat.
AB  - The potential neuroprotective effects of the novel nitro-derivate of aspirin
      (NCX4016) on permanent focal cerebral ischemia in spontaneously hypertensive rats
      (SHRs) was investigated. Reference compounds were acetylsalicilic acid (ASA) and
      FK506 (tacrolimus). Ten minutes after surgery, SHRs were randomly divided into
      four groups of ten, pharmacologically treated and sacrificed 24 h after
      treatment. Brains were removed and processed to measure infarct volume, 70 kDa
      heat shock protein (hsp70), glial fibrillary acidic protein (GFAP) and vimentin
      (Vim) immunoreactivity (IR), and apoptosis using terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. NCX
      4016 significantly reduced total infarct volume compared to ASA (-20%, P < 0.05),
      FK506 (-18%, P < 0.05) and vehicle treatment (-20%, P < 0.05). Experimental
      groups did not differ in hsp70-IR and GFAP-IR. Conversely, hyperplastic
      astrocytes, measured by Vim-IR, were significantly lower in NCX-4016 than in the
      vehicle group (-36%, P<0.01). TUNEL assay indicated a significantly lower degree
      of apoptosis in NCX-4016 group than vehicle in both the homolateral (-27%, P <
      0.01) and contralateral hemisphere (-29%, P < 0.05). These findings indicate that
      NO release associated with aspirin confers neuroprotective effects against
      ischemic injury.

PMID- 11290404
TI  - Aberrant cytokine gene expression in the hippocampus in murine systemic lupus
      erythematosus.
AB  - Cytokines are important mediators of immune regulation and have been implicated
      in the pathogenesis of the neurological disturbances, which occur in up to sixty
      percent of patients with systemic lupus erythematosus (SLE). SLE is an autoimmune
      disease characterized by the presence of autoantibodies against nuclear antigens,
      including native DNA. Cytokines are thought to drive autoantibody production in
      lupus. Certain of the derangements in memory and learning described in human and
      experimental SLE map to the hippocampus. The current study examines the
      expression of cytokine genes in the hippocampus in lupus, using MRL-lpr/lpr mice
      as the experimental model. These mice spontaneously develop a SLE-like illness
      accompanied by disturbances in spatial learning. Our results suggest a potential
      role for proinflammatory cytokines in the cognitive aberrations observed in
      lupus.

PMID- 11290405
TI  - Effect of 6-hydroxydopamine or repeated amphetamine treatment on mesencephalic
      mRNA levels for AMPA glutamate receptor subunits in the rat.
AB  - Expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subunit
      mRNAs were assayed in the ventral mesencephalon of rats that received either a
      unilateral microinjection of the dopamine neurotoxin 6-hydroxydopamine (6-OHDA;
      Experiment 1) or repeated treatment with amphetamine (Experiment 2). GluR2 levels
      were decreased 1 and 3 days after the lesion, and GluR1 and GluR3 levels also
      showed a transient decrease at 1 day after the lesion. Repeated amphetamine
      treatment did not significantly alter GluR1-4 levels measured 30 min after the
      third or tenth amphetamine injection, even though locomotor sensitization was
      obtained. Thus, while the present results indicate that AMPA receptor subunits
      are associated with dopamine-containing cell bodies in the ventral mesencephalon,
      these transcripts may not be responsible for the development of amphetamine
      sensitization.

PMID- 11290406
TI  - Separation of signal and noise from in vivo optical recording in Guinea pigs
      using independent component analysis.
AB  - Optical recording in vivo severely suffers from the interference of heartbeat
      noise. So far, heartbeat noise has been minimized by subtracting from each
      experimental trial an average of interlaced control recordings. This method,
      however, is time-consuming and increases tissue damage due to phototoxicity. Here
      we applied independent component analysis (ICA) to in vivo optical recordings,
      for separation of auditory signals and noises. Our results show that ICA can be
      successfully used to separate sound-evoked signals and heartbeat noises. Compared
      with the previous method, ICA has a comparable power of separation and does not
      require background recordings.

PMID- 11290407
TI  - Changes in thiol content and expression of glutathione redox system genes in the
      hippocampus and cerebellum in Alzheimer's disease.
AB  - In this report, we compared total and protein-bound thiol levels in the
      hippocampus and cerebellum of six Alzheimer's disease (AD) patients and six age
      matched control subjects. Total level of sulfhydryl (SH) groups, determined using
      the 5,5'-dithiobis(2-nitrobenzoic acid) method, was not significantly altered in
      the hippocampus and cerebellum of AD patients. The level of protein-bound SH
      groups, determined by labeling with 3-(N-maleimido-propionyl) biocytin, was
      decreased in the AD hippocampus compared with controls. Reverse transcription
      polymerase chain reaction analysis of the expression of key glutathione redox
      system genes demonstrated the induction of glutathione reductase and glutathione
      peroxidase messages in the AD hippocampus. Levels of glutathione transferase mu
      and A4-4 messages were unchanged. This study suggests that protective antioxidant
      gene responses are insufficient to counteract the increased oxidative damage of
      proteins in a vulnerable region of the AD brain.

PMID- 11290408
TI  - Cultured glial cells are resistant to the effects of motor neurone disease
      associated SOD1 mutations.
AB  - Free radical damage has been implicated in the pathophysiology of motor neurone
      disease (MND); mutations have been identified in the gene encoding Cu/Zn
      superoxide dismutase (SOD1). There is evidence that glial cell dysfunction may
      contribute to motor neurone injury, but the exact role of glial cells in MND has
      yet to be established. The aim of this study was to determine whether expression
      of mutant SOD1 affects the response of glia to oxidative stress. Stable C6 glioma
      cells expressing mutant SOD1 and cortical astrocyte cultures from G93A-SOD1
      transgenic mice were exposed to: xanthine/xanthine oxidase; hydrogen peroxide;
      A23187 and 3-morpholinosydonimine. Cell viability was measured using the 3-(4,5
      dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Neither C6 glioma
      cells nor cortical astrocytes expressing mutant SOD1 were more susceptible to any
      of the free radical generating systems compared to control cells. These results
      suggest that astrocytes are resistant to the toxic effects of mutant SOD1 widely
      reported for neuronal cells.

PMID- 11290409
TI  - Exposure of a 'witness rat' to one treated with beta-carboline FG 7142 does not
      increase dopamine turnover in the medial prefrontal cortex of the 'witness rat'.
AB  - A method for selectively activating the dopaminergic field of the prefrontal
      cortex would be highly useful for studies of mesocortical dopamine systems. When
      a rat ('witness' rat) is exposed to a rat that is undergoing footshock,
      prefrontocortical dopamine metabolism is selectively increased in the witness
      rat. Since the anxiogenic beta-carboline FG 7142 mimics many of the effects of
      footshock, we hypothesized that exposure of a witness-rat to a rat treated with
      FG 7142 would also increase dopamine metabolism in the prefrontal cortex. We
      found that while as expected, FG 7142 itself increased prefrontal cortex dopamine
      metabolism, there was no significant change in dopamine metabolism in the witness
      rat. Thus exposure to a rat treated with FG 7142 does not selectively activate
      the mesocortical dopamine system.

PMID- 11290410
TI  - Insulin-like growth factor 1 inhibits glucocorticoid-induced glutamine synthetase
      activity in cultured L6 rat skeletal muscle cells.
AB  - We previously demonstrated the preventive effect of insulin-like growth factor 1
      (IGF-1) on steroid myopathy in rats. However, the mechanism by which IGF-1
      inhibits steroid myopathy remains unclear. Recent studies have revealed that
      glutamine synthetase (GS) is induced by glucocorticoid and may be related to the
      development of steroid myopathy. In this study, we examined whether IGF-1
      affected steroid-induced enhancement of GS activity in L6 rat skeletal muscle
      cells. Dexamethasone (10(-6) M) significantly increased GS activity in L6 cells
      (P < 0.01). IGF-1 dose-dependently inhibited dexamethasone-induced GS activity.
      Addition of IGF-1 (750 ng/ml) decreased GS activity to approximately 50% of that
      with dexamethasone alone (P < 0.01). These results suggest that a decrease in GS
      activity may be involved in the preventive effect of IGF-1 on steroid myopathy.

PMID- 11290411
TI  - Anxiety affects the postural sway of the antero-posterior axis in college
      students.
AB  - To examine whether the postural balance is influenced by the degree of anxiety,
      body sway during orthostatic standing while gazing at a visual target was
      examined in college students. Students, physically and mentally healthy, were
      divided into two groups according to the degree of state anxiety; high anxiety
      group (HA) and low anxiety group (LA). A fast Fourier transform analysis of the
      postural sway in antero-posterior axis showed that frequency components of 0.02
      0.21 Hz, reflecting vestibular inputs, were 16% greater and those of 2.02-10.0
      Hz, reflecting somatosensory inputs, were 24% smaller in HA. These differences
      between HA and LA were abolished when the eyes were closed. It is concluded that
      the interactions of visual inputs with vestibular and somatosensory inputs are
      influenced by anxiety.

PMID- 11290414
TI  - Cloning and characterization of a novel serine/threonine protein phosphatase type
      5 from Trypanosoma brucei.
AB  - Reversible protein phosphorylation is essential for the regulation of numerous
      cellular functions and differentiation. The haemo-flagellated parasitic protozoan
      Trypanosoma brucei, the causative agent for African trypanosomiasis undergoes
      various stages of cellular differentiation during its digenetic life cycle. A
      complete cDNA of a unique serine/threonine phosphatase type five (TbPP5) was
      cloned and characterized from T. brucei. TbPP5 contains an open reading frame of
      1416 bp that encodes a protein of about 53 kDa and exists as a single copy gene
      in the T. brucei genome. The deduced amino acid sequence showed 45-48% overall
      identity and 60-65% similarity with protein phosphatase 5's (PP5) from different
      species. Analysis of the primary sequence revealed that TbPP5 contains three TPR
      motifs at the N-terminal region (amino acid residues 7-107) while the phosphatase
      catalytic domain occurs in the C-terminal region (amino acid residues 210-410). A
      TbPP5 cDNA hybridized with a transcript of 2.5 kb which is present at similar
      levels in the procyclic and the bloodstream forms. However, the level of
      expression of the TbPP5 protein (52 kDa) detected by an antibody developed
      against a recombinant protein produced in E. coli was about 2-fold higher in the
      procyclic than the bloodstream form. The TbPP5 transcript level gradually
      decreased in cells grown in the logarithmic phase to the stationary phase in
      culture. Moreover, 18 h serum starvation of the procyclic forms decreased the
      level of the specific transcript about 3-fold suggesting that this protein may
      play a role during the active growth phase of the organism. The recombinant
      protein showed phosphatase activity which was stimulated about 2.6-fold by
      arachidonic acid with half-maximal activity at 75 microM. Indirect immuno
      fluorescence of permeabilized cells revealed that the protein is localized in the
      cytosol and the nucleus This is the first report for the identification of a type
      5 serine/threonine protein phosphatase in an ancient eukaryote such as T. brucei.

PMID- 11290415
TI  - Genomic structure and chromosomal mapping of the gene coding for ICBP90, a
      protein involved in the regulation of the topoisomerase IIalpha gene expression.
AB  - We have recently identified a novel CCAAT box binding protein (ICBP90) involved
      in the regulation of topoisomerase IIalpha gene expression. We have observed that
      it is expressed in non-tumoral proliferating human lung fibroblast cells whereas
      in HeLa cells, a tumoral cell line, ICBP90 was still present even when cells were
      at confluence. In the present study, we have determined the ICBP90 gene structure
      by screening of a human placenta genomic library and PCR analysis. We report that
      the ICBP90 gene spans about 35.8 kb and contains six coding exons named A to F.
      In the 5' upstream sequence of the region containing the coding exons, two
      additional exons (I and II) were found. Additionally, an internal splicing site
      was found in exon A. A promoter region, including three putative Sp1 binding
      sites between exons I and A, was identified by transient transfection. Northern
      blot analysis of several cancer cell lines revealed the existence of two ICBP90
      mRNA species of 5.1 and 4.3 kb that are transcribed from the gene. The relative
      amounts of these mRNAs depended on the cell type. In MOLT-4 cells and Burkitt's
      lymphoma Raji cells, the 4.3 kb or the 5.1 kb transcripts were mainly observed,
      respectively. In other cell lines, such as HL-60 cells, chronic myelogenous
      leukaemia K-562, lung carcinoma A549, HeLa or colorectal SW480, both 4.3 and 5.1
      kb forms of ICBP90 mRNA could be detected. Interestingly, western blot analysis
      showed several ICBP90 protein bands in HeLa but only a single band in MOLT-4 cell
      extracts. Taken together our results are consistent with the ICBP90 gene
      exhibiting alternative splicing and promoter usage in a cell-specific manner.

PMID- 11290417
TI  - The human ITGB4BP gene is constitutively expressed in vitro, but highly modulated
      in vivo.
AB  - The ITGB4BP gene encodes for a highly conserved protein, named p27BBP (also known
      as eIF6), originally identified in mammals as a cytoplasmic interactor of beta4
      integrin. In vitro and in vivo studies demonstrated that p27BBP is essential for
      cell viability and has a primary function in the biogenesis of the 60S ribosomal
      subunit. Here we report the genomic organization of the human ITGB4BP gene and
      show that its gene product is expressed with features of a housekeeping element
      in vitro, but is regulated in a cell specific fashion in vivo. The human gene
      spans 10 kb and comprises seven exons and six introns. The 5' flanking region
      shows a TATA-less promoter, canonical CpG islands, and binding sites for serum
      responsive elements. In cultured cells, p27BBP mRNA and protein are
      constitutively expressed and stable. A gradual loss of p27BBP mRNA can be
      observed only after prolonged serum starvation, and heat shock treatment. In
      contrast, p27BBP mRNA and protein levels in vivo are variable among different
      organs. More strikingly, immunohistochemical analysis shows that the p27BBP
      protein is present in a cell specific fashion, even within the same tissue. Taken
      together, these data show that ITGB4BP gene expression is highly regulated in
      vivo, possibly by the combination of tissue specific factors and protein
      synthesis pathways.

PMID- 11290416
TI  - Characterization of a heavy metal ATPase from the apicomplexan Cryptosporidium
      parvum.
AB  - P1-ATPases are transporters which pump heavy metals across membranes, either to
      provide enzymes with essential cofactors or to remove excess, toxic metal cations
      from the cytosol. The first protist P1-ATPase (CpATPase2) has been isolated from
      the apicomplexan Cryptosporidium parvum, an opportunistic pathogen of AIDS
      patients. This single copy gene encodes 1260 amino acids (aa), predicting a
      protein of 144.7 kDa. Reverse transcription-polymerase chain reaction (RT-PCR)
      and western blot analysis confirmed CpATPase2 expression. Immunofluorescence
      microscopy of C. parvum sporozoites using rabbit antiserum raised against a
      glutathione-S-transferase (GST) fusion protein suggests that CpATPase2 is
      associated with the plasma- and cytoplasmic membranes. The protein shares
      greatest overall sequence similarity to previously characterized copper P1
      ATPases. Expression and subsequent biochemical analyses of the N-terminal heavy
      metal binding domain (HMBD, GMxCxxC) of CpATPase2 as a maltose-binding protein
      (MBP) in Escherichia coli reveals that the protein specifically binds reduced
      copper, Cu(I), in vitro and in vivo, and that the cysteine residues of HMBD are
      responsible for heavy metal coordination. Overall, these data show that the
      apicomplexan C. parvum possesses a heavy metal P-ATPase transporter with a
      specificity for reduced copper. Since this discovery represents the first time a
      heavy metal P-ATPase has been identified and characterized from a protist,
      further molecular and biochemical studies are needed to understand the roles
      heavy metal P-ATPases play in heavy metal metabolism and potential virulence for
      this and other apicomplexa.

PMID- 11290419
TI  - Expression and sequence analysis of the Blumeria graminis mitogen-activated
      protein kinase genes, mpk1 and mpk2.
AB  - Mitogen-activated protein (MAP) kinases represent a group of serine/threonine
      kinases which play a pivotal role in signal transduction processes in eukaryotic
      cells. Using degenerate PCR primer design based on published and aligned MAP
      kinase sequences we have cloned and characterised two MAP kinase genes from the
      barley powdery mildew fungus, Blumeria graminis. We have utilised 'step down' PCR
      to attain the full length mildew genomic clones. The single-copy genes, named
      mpk1 and mpk2, encode putative proteins of 356 and 410 amino acids and carry
      three and four introns, respectively. Expression studies, using RT-PCR, reveal a
      differing pattern of tissue gene expression with mpk1 and mpk2 during germling
      morphogenesis and this is compared with the constitutive expression of the
      'control' beta-tubulin gene.

PMID- 11290418
TI  - Identification and characterization of the human MOG1 gene.
AB  - Many of the proteins that mediate transport into and out of the nucleus have been
      structurally and functionally conserved throughout evolution. Here we describe
      the sequence and characterization of the human MOG1 gene. The MOG1 gene was
      originally identified in Saccharomyces cerevisiae as a multi-copy suppressor of
      conditional alleles of the yeast nuclear transport factor, GSP1 (scRan) (Oki and
      Nishimoto (1998) Proc. Natl. Acad. Sci. USA 95, 15388-15393). A search of the
      expressed sequence tag database identified a putative human protein that is 29%
      identical and 47% similar to the yeast protein. Our experiments demonstrate that
      the human MOG1 message is expressed in a variety of tissue samples. Several
      experiments indicate that the human MOG1 protein binds to both yeast and human
      Ran suggesting functional conservation between the yeast and human MOG1 proteins.
      Furthermore, hMOG1a, like scMOG1, is localized throughout the cell but is
      concentrated within the nucleus. Consistent with these findings, hMOG1a can
      partially complement the growth defect present in yeast MOG1 deletion cells.
      Taken together, our findings suggest that MOG1 is an evolutionarily conserved Ran
      binding protein that could play a role in regulating nuclear protein trafficking.

PMID- 11290420
TI  - Mouse Trefoil factor genes: genomic organization, sequences and methylation
      analyses.
AB  - The mammalian Trefoil Factors (TFFs), TFF1/pS2, TFF2/SP and TFF3/ITF, are
      expressed and secreted throughout the gastrointestinal tract with a specific and
      complementary pattern. These proteins exhibit common functions in the protection
      and repair process of the gastrointestinal epithelial barrier. Here, we report
      the clustered organization of the three mouse TFF genes in a 40 kb DNA segment,
      in a head to tail orientation in the following order: TFF1, TFF2, and TFF3.
      Computer comparison of the mouse TFF promoter sequences to their human
      counterparts revealed conserved boxes in both mouse and human genes. Promoter
      methylation analyses showed that, in tissues where these genes are normally
      expressed, the proximal promoters of TFF1 and TFF2 are specifically not
      methylated and that of TFF3 is partially demethylated. In contrast, in organs
      that do not express TFFs, the promoters of the three genes are methylated. These
      findings strongly argue for the involvement of epigenetic mechanisms in the
      regulation of TFF expression in normal and pathological conditions.

PMID- 11290421
TI  - Cloning and expression of a down-regulated gene (TrEnodDR1) of white clover
      responded by the nod genes derived from Rhizobium leguminosarum bv. trifolii
      strain 4S.
AB  - The nodulation genes of Rhizobium leguminosarum bv. trifolii 4S (strain 4S) were
      cloned into cosmid vector pLAFR1 named pC4S8 which was contained nodNMLFEDABCIJ
      and a part of nodT as an insert. The pC4S8 was transferred to strain H1, Sym
      plasmid (pRt4Sa) cured strain of strain 4S, and isolated as Tc resistant and
      nodulation restored mutant, strain H1(pC4S8). During infection process of this
      strain, visible symbiotic features, such as root hair curling (Hac), root hair
      deformation (Had) and infection thread formation (Inf) were also restored. The
      nodule forming ability of strain H1(pC4S8) was increased 3-4 times in nodule
      number than that of strain 4S. Then, to investigate the effect of Rhizobium nod
      genes on the host plant (Trifolium repens L.) gene expression, cDNAs which were
      responded to the inoculation of rhizobia were differentially screened based on
      the presence or absence of nod genes treated with strains H1(pC4S8) or H1,
      respectively. The cDNA, TrEnodDR1 (Trifolium repens early nodulin down regulation
      1) gene was isolated from cDNA library prepared from white clover seedlings
      treated with nod- strain H1, but didn't exhibit in nod+ treated cDNA library, as
      a down-regulated gene. Expression analysis of TrEnodDR1 was performed in various
      tissues of white clover, it is suppressed in root nodule and also strongly
      suppressed by the inoculation of rhizobia in the seedlings. It is discussed that
      TrEnodDR1 gene is suppressed when the white clover comes into symbiosis with
      rhizobia.

PMID- 11290422
TI  - Differential RNA expression of alpha-expansin gene family members in the
      parasitic angiosperm Triphysaria versicolor (Scrophulariaceae).
AB  - Haustoria are parasitic plant specific organs that locate, attach to, and invade
      host plant tissues. Parasitic species of the Scrophulariaceae develop haustoria
      on their roots in response to chemical signals released by host plant roots.
      Haustorium development was induced in vitro in roots of the parasitic
      Scrophulariaceae Triphysaria versicolor by treating them with exudates obtained
      from maize roots, the chemical 2,6-dimethoxybenzoquinone (DMBQ) or the cytokinin
      6-benzylaminopurine (BAP). Morphological responses of T. versicolor roots to
      these haustoria inducing factors (HIFs) included localized swelling and epidermal
      hair proliferation near the root tips. These responses were not observed when
      roots of the non-parasitic Scrophulariaceae Lindenbergia muraria were similarly
      treated. Because expansin proteins are closely associated with plant cell wall
      expansion and growth, we examined the expression of expansin genes in response to
      HIFs. We isolated cDNAs homologous to transcripts encoding three distinct alpha
      expansin proteins in T. versicolor. Northern-blot analyses indicated that these
      transcripts were differentially abundant in different tissues. Steady-state
      levels of two expansin transcripts increased in T. versicolor roots exposed to
      BAP, but not DMBQ or maize root exudates. Expansin transcript abundance also
      increased in L. muraria in response to BAP treatment. These results suggest that
      the expansins examined fulfill functions distinct from haustorium development.

PMID- 11290423
TI  - Sequence, genomic structure and tissue expression of Human BRI3, a member of the
      BRI gene family.
AB  - The BRI3 gene is a member of the BRI gene family, made up of at least three
      different genes (BRI1-3). Previous studies established the cDNA sequence and
      structure of the human and mouse BRI1 and BRI2 genes and we recently reported
      that mutations in the BRI2 isoform, located on chromosome 13, are associated with
      dementia in humans. In the present work, we determine the complete cDNA sequence
      and genomic organization of the human BRI3 gene. BRI3 codes for a polypeptide of
      267 amino acids, with a Mr of 30 KDa and a pI of 8.47. The amino acid sequence is
      43.7% identical to the sequence of the human BRI2, and 38.3% identical to that of
      human BRI1, with the highest percentage of amino acid identity being concentrated
      on the C-terminal half of the molecules. In Northern blots, BRI3 cDNA hybridizes
      only one message of approximately 2.1 kilobases, which is predominantly present
      in the human brain. The BRI3 gene is localized on chromosome 2 and consists of
      six exons spanning more than 20 kb. Homology search of EST data banks retrieved a
      Caenorhabditis briggsae homolog of BRI, indicating that the BRI gene belongs to a
      strongly conserved gene family. These studies, aimed at characterizing the
      members of the BRI gene family, may provide valuable clues to the understanding
      of their normal function and how mutations in BRI2 can cause neurodegeneration
      and dementia similar to Alzheimer's disease.

PMID- 11290424
TI  - The C. elegans gon-2 gene encodes a putative TRP cation channel protein required
      for mitotic cell cycle progression.
AB  - The C. elegans gon-2 gene is required for the post-embryonic mitotic cell
      divisions of the gonadal precursor cells. A single major transcript of
      approximately 6.7 kb is derived from the gon-2 locus. This mRNA encodes a protein
      related to the TRP family of cation channels and has a high degree of similarity
      to several vertebrate genes, including melastatin. Mutant alleles of gon-2 affect
      evolutionarily conserved amino acid residues. Northern analyses suggest that gon
      2 expression is not limited to gonadal tissues.

PMID- 11290425
TI  - Conservation of the MORF4 related gene family: identification of a new chromo
      domain subfamily and novel protein motif.
AB  - The seven member, human MORF4 related gene (MRG) family was recently identified
      based on the ability of Mortality factor on chromosome 4 (MORF4) to induce
      replicative senescence in immortal cell lines assigned to complementation group B
      (Bertram et al., 1999. Mol. Cell Biol. 19, 1479-1485). Initial computer based
      similarity searches identified human retinoblastoma binding protein 1 (RBP-1),
      Drosophila melanogaster male specific lethal-3 (Msl-3), S. pombe altered polarity
      13 (Alp13) and S. cerevisiae Eaf3p, a component of the yeast NuA4 HAT complex
      (Galarneau et al., 2000. Mol. Cell 5, 927-937), as having similarity to the human
      MRG protein family. This suggested that the MRG family might be found in multiple
      species, and analysis of other homologs would provide functional and evolutionary
      insights into this gene family. Here, we report that MRG family members are
      present in twenty-three species based on molecular assays and sequence similarity
      searches. The new family members were divided into two groups based on similarity
      to the predominant human MRG family members, MRG15 and MRGX. The family members
      similar to MRG15 define a new, highly conserved subsection of the chromo domain
      superfamily. Additionally, conservation in the C-terminal two thirds of all the
      MRG family members and the Drosophila and human MSL-3 proteins defines a new
      protein domain, the MRG domain. These results indicate a highly conserved role
      for the MRG family in transcriptional regulation via chromatin remodeling by
      histone acetylation.

PMID- 11290426
TI  - Genomic organization of the gene for mouse PIASgamma and analysis of its
      promoter.
AB  - Signal transducer and transcriptional activator (STAT) proteins are latent
      cytoplasmic transcription factors that are activated in response to stimulation
      by various cytokines. Protein Inhibitors of Activated STAT (PIAS) proteins
      comprise a family of five mammalian proteins which have been identified as
      potentially important downregulators of the STAT signaling pathway. We have
      previously reported the identification and expression of the mouse homologue of
      PIAS family member PIASgamma. Here we report the isolation by genomic 5'-RACE PCR
      and in vitro analysis of the mouse PIASgamma promoter region and the genomic
      structure and organization of the mouse and human PIASgamma genes. Human
      PIASgamma spans approximately 23 kb on chromosome 19 and is organized into ten
      exons. The size of mouse PIASgamma is 16 kb and also organized into ten exons
      with the intron/exon structure of the two genes conserved in both species. As a
      result, considerable conservatism of the mouse and human intron sequences was
      observed. Analysis of a 1.4 kb genomic fragment containing the mouse PIASgamma
      promoter allowed us to map the transcription 'Start' site of the gene, determine
      the sequences essential for the activity of this promoter and to define a minimal
      promoter region.

PMID- 11290427
TI  - Murine Xist RNA isoforms are different at their 3' ends: a role for differential
      polyadenylation.
AB  - Murine Xist is an essential transcript for X chromosome inactivation (X
      inactivation). According to recently revised structure, Xist is at least 17.8 kb
      long. It consists of seven exons and there are two major transcripts in female
      somatic cells. In this study we further defined the molecular structures of the
      two isoforms, namely short (S) and long (L) forms by northern blot and RNAse
      protection assay (RPA). The following lines of evidences suggest that mouse Xist
      depends on differential polyadenylation, not alternative splicing, to generate
      the two RNA isoforms: (1) only one band was detectable with the northern probes
      spanning the 3' end of Xist. (2) RPA showed the 3' termini of both S and L forms,
      and there are putative polyadenylation signals and hairpin structures close to
      these ends. (3) Analyses by splice site prediction program did not show any
      evidence of splice motifs in the sequence of L form. (4) Alignments between Xist
      3' end (ESTs) and genomic sequence support the absence of splicing event in the
      region. The newly revised structure of Xist isoforms may have different stability
      and roles in the process of X inactivation.

PMID- 11290428
TI  - Molecular cloning of the orphanin FQ receptor gene and differential tissue
      expression of splice variants in rat.
AB  - Pharmacological and receptor-ligand binding studies of the cloned orphanin FQ
      (OFQ) receptor suggest that multiple forms of this receptor may exist. To further
      characterize the OFQ receptor (OFQR), we attempted to isolate the gene encoding
      this receptor in rat. The OFQR gene exceeds 10 kb in length and contains six
      exons ranging from 34 to 524 bp that are interrupted by five introns. The ATG
      translation initiation codon is located in exon 2, and the open reading frame
      consists of 1283 bp. Primer extension analysis of the gene revealed two major
      transcription initiation sites: one in the 5' flanking region and the other in
      intron 1. The rat OFQR gene appeared to be alternatively spliced to yield
      multiple mRNAs. Four splice variants deleted for exon 1 were expressed only in
      brain. In contrast, five isoforms containing exon 1 were expressed in various
      tissues, such as brain, testes, and gastrointestinal tract. These data suggest
      that unique regions in intron 1 and in the 5' flanking region of the OFQR gene
      contribute to the regulation of its expression in different tissues.

PMID- 11290429
TI  - Simple and efficient vectors for retrofitting BACs and PACs with mammalian neoR
      and EGFP marker genes.
AB  - Bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs) are
      widely used to investigate the functions of genes and genomes in mammalian cells
      in vitro and in vivo. We have developed a series of vectors which can simply and
      efficiently be retrofitted onto BACs or PACs. These vectors carry a neoR gene for
      selection in cells in tissue culture, including ES cells, and also an EGFP gene
      driven by the strong CAG promoter for quick detection of the DNA in cells. All
      the plasmids are retrofitted using the loxP site and Cre recombinase and some
      carry the gamma origin of plasmid R6K which does not function in commonly used
      bacteria such as DH10B. Retrofitting of PACs and BACs carrying alphoid DNA was
      very efficient with almost no rearrangement of the highly repetitive alphoid DNA.
      Following transfer into HT1080 cells and mouse oocytes in tissue culture the DNA
      could easily be monitored by the EGFP fluorescence.

PMID- 11290430
TI  - Chronic myeloid leukaemia. STI 571 magnifies the therapeutic dilemma.

PMID- 11290431
TI  - The significance of dihydropyrimidine dehydrogenase (DPD) activity in bladder
      cancer.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the pathway
      of uracil and thymine catabolism. DPD is also the principal enzyme involved in
      the degradation of 5-fluorouracil (5-FU), which is one of the anticancer
      chemotherapeutic agents currently used in the treatment of bladder cancer. Little
      is known about the significance of DPD activity in human cancers. We investigated
      the activity of DPD in 74 bladder cancers and the relationship between the DPD
      activity and the sensitivity to 5-FU. The levels of DPD activity in bladder
      cancer and normal bladder tissues were determined by the 5-FU degradation assay.
      The sensitivity to 5-FU was assessed by the microculture tetrazolium dye
      (dimethylthiazolyl-2-5-diphenyltetrazolium bromide; MTT) assay. The activity of
      DPD was approximately 2-fold higher in bladder cancer tissues compared with
      normal bladder tissues. DPD activity in invasive bladder cancers was
      approximately 2-fold higher than that in superficial cancers. In addition, the
      levels of DPD activity in grade 2 and grade 3 bladder cancers were approximately
      3-fold and 4-fold higher than that in grade 1 cancers, respectively. Patients
      with superficial bladder cancer with a low DPD activity had a slightly longer
      postoperative tumour-free period than those with a high DPD activity over a 2
      year follow-up period, but this was not significant. There was an inverse
      correlation between DPD activity in bladder cancer cells and their sensitivity to
      5-FU. Furthermore, 5-chloro-2,4-dihydroxypyridine (CDHP), a potent DPD inhibitor,
      enhanced the sensitivity to 5-FU. The present study has demonstrated that the
      level of DPD activity correlated with the progression of the stage and an
      increase in the grade of the bladder cancer. These results suggest that an
      elevated DPD activity might be associated with the malignant potential of the
      bladder cancer. In addition, it might be possible to overcome 5-FU insensitivity
      by using DPD inhibitors in the treatment protocols of 5-FU-based chemotherapy for
      bladder cancers.

PMID- 11290432
TI  - Stage I non-seminomatous germ-cell tumours of the testis: identification of a
      subgroup of patients with a very low risk of relapse.
AB  - There is no consensus about a reproducible prognostic model capable of
      distinguishing between clinical stage I non-seminomatous germ cell tumour (NSGCT)
      carrying a high and low risk of relapse. The aim of this study was to assess the
      prognostic value of histological parameters in patients with stage I NSGCT
      undergoing surveillance after orchiectomy. We retrospectively evaluated tumour
      specimens from 88 consecutive stage I NSGCT patients undergoing surveillance in
      our institution between 1984 and 1996. 24 patients relapsed (27%). Multivariate
      analysis singled out vessel invasion (VI) (relative risk (RR)=3.8; 95% confidence
      interval (CI) 1.4-10.4) and the presence of mature teratoma (RR= 0.2; 95% CI 0.1
      0.6) as independently correlated with relapse-free survival (RFS). Patients can
      be classified accordingly into three prognostic groups with a low (27 patients
      with mature teratoma but without VI), intermediate (34 patients with both VI and
      mature teratoma or with neither VI or mature teratoma) and a high risk (23
      patients with VI, but without mature teratoma) of relapse. Relapse rates in these
      three groups were 0%, 29% (95% CI: 23-35%) and 61% (95% CI: 55-67%),
      respectively. This prognostic index, based on two standard pathological
      parameters, identified a subgroup with a very low risk of relapse that represents
      approximately one third of stage I patients. Patients who belong to this subgroup
      should be managed by surveillance only, instead of retroperitoneal lymph node
      dissection (RPLND) or adjuvant chemotherapy.

PMID- 11290434
TI  - Prognostic factors in breast cancer: the predictive value of the Nottingham
      Prognostic Index in patients with a long-term follow-up that were treated in a
      single institution.
AB  - The Nottingham Prognostic Index (NPI) is an index, derived from a retrospective
      multivariate study, that is able to predict survival in patients with breast
      cancer. The index is based on tumour size, lymph node stage and histological
      grade and allows the stratification of patients into three different prognostic
      groups. The aim of this study was to verify, according to our experience with a
      long-term follow-up, the effect of some prognostic variables on survival and to
      establish the independent influence of each of them by means of a survival
      regression analysis. Then we applied the NPI to the same group of patients in
      order to assess the predictive power and reproducibility of the index. 402
      patients treated from January 1979 to December 1987 were evaluated. In
      multivariate analysis (Cox proportional hazard model), only size, lymph node
      involvement and histological grade remained independent prognostic factors. The
      survival curves obtained after applying the NPI are similar to those for the
      factors with independent prognostic significance derived from our multivariate
      analysis. Our improved survival rates may be attributed to the administration of
      adjuvant therapies to a larger number of patients. The NPI allow us to accurately
      predict prognosis and we advocate its more common use.

PMID- 11290433
TI  - Gemcitabine and vinorelbine as first-line chemotherapy for advanced non-small
      cell lung cancer: a phase II trial.
AB  - The purpose of this phase II study was to investigate the efficacy and safety of
      gemcitabine plus vinorelbine as first-line chemotherapy in patients with advanced
      non-small cell lung cancer (NSCLC). Eligibility criteria included cytologically
      or histologically confirmed NSCLC (stage IIIB or IV), no previous chemotherapy,
      and bidimensionally measurable disease. Patients received 1000 mg/m(2)
      gemcitabine and 30 mg/m(2) vinorelbine on days 1, 8 and 15 every 4 weeks up to
      eight courses. From December 1997 to November 1998, 70 patients (59 stage IV and
      11 stage IIIB disease), with a median age of 59 years (range 38-74 years) were
      enrolled. The intent-to-treat response rate was 41% (95% confidence interval (CI)
      30-54%) with 1 complete responder (CR) and 28 partial responders (PRs), 15
      patients had stable disease (SD) and 26 progressed (PD). Median survival was 8.3
      months (95% CI 6.0-9.9 months), median progression-free survival (PFS) was 4.8
      months (95% CI 3.9-5.5 months), and 1-year survival rate was 33.5% (95% CI 24.0
      46.8%). Patients received a total of 229 cycles. Haematological and non
      haematological toxicities were moderate. Transient World Health Organization
      (WHO)-grade IV leucopenia and thrombocytopenia occurred in 13 (6%) and two (1%)
      cycles, respectively. The predominant non-haematological toxicity was local
      reactions of the veins in 19 (27%) patients (WHO-grade II and III). Neurotoxicity
      was infrequent, non-cumulative, and reversible. The combination of gemcitabine
      and vinorelbine has demonstrated activity in metastatic NSCLC, with response and
      survival rates similar to those of cisplatin-based regimens and a more favourable
      toxicity profile that is well tolerated in an outpatient setting.

PMID- 11290435
TI  - Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil
      plus leucovorin in a phase III trial conducted in patients with advanced
      colorectal carcinoma.
AB  - Standard therapy for advanced or metastatic colorectal cancer consists of 5
      fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.).
      Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially
      activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and
      is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather
      than intravenous treatment may affect medical resource use because the two
      regimens do not require the same intensity of medical intervention for drug
      administration, and have different toxicity profiles. Here we examine medical
      resource use in the first-line treatment of colorectal cancer patients with
      capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In
      a prospective, randomised phase III clinical trial, 602 patients with advanced or
      metastatic colorectal cancer recruited from 59 centres worldwide were randomised
      to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition
      to clinical efficacy and safety endpoints, data were collected on hospital visits
      required for drug administration, hospital admissions, and drugs and unscheduled
      consultations with physicians required for the treatment of adverse events.
      Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma
      resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved
      safety including less stomatitis and myelosuppression. Capecitabine patients
      required substantially fewer hospital visits for drug administration than 5-FU/LV
      patients. Medical resource use analysis showed that patients treated with
      capecitabine spent fewer days in hospital for the management of treatment related
      adverse events than did patients treated with 5-FU/LV. In addition, capecitabine
      reduced the requirement for expensive drugs, in particular antimicrobials
      fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with
      an oral home-based therapy patients receiving capecitabine needed more frequent
      unscheduled home, day care, office and telephone consultations with physicians.
      In the light of clinical results from the phase III trial demonstrating increased
      efficacy in terms of response rate, equivalent time to progression (TTP) and
      survival (OS), and a superior safety profile, the results from this medical
      resource assessment indicate that capecitabine treatment of colorectal cancer
      patients results in a substantial resource use saving relative to the Mayo Clinic
      regimen of 5-FU/LV. This benefit is derived principally from the avoidance of
      hospital visits for i.v. drug administration, less expensive drug therapy for the
      treatment of toxic side-effects, and fewer treatment-related hospitalisations
      required during the course of therapy for adverse drug reactions in comparison to
      patients treated with 5-FU/LV.

PMID- 11290436
TI  - Adult height and age at menarche in childhood cancer survivors.
AB  - The aim of this study was to assess the long-term effects of cancer treatments on
      adult height and age at menarche in survivors of various types of childhood
      cancer. 285 childhood cancer survivors (161 men and 124 women), at least 18 years
      old and having been off treatment for at least 5 years, were examined. The
      effects of cranial (CrRT) and craniospinal irradiation (CrSpRT), other treatments
      and age at diagnosis on adult height and age at menarche were investigated.
      Patients who did not receive CrRT or CrSpRT, reached normal adult heights.
      However, a significant reduction in adult height was observed in men and women
      treated with CrRT or CrSpRT, especially if the treatment was given at the age of
      8 years or younger. In girls, CrRT resulted in a significantly earlier menarche,
      compared with the Dutch population. Chemotherapy, radiation dose and age at
      menarche did not affect adult height. The relative risk (RR) of attaining an
      adult height below the 3rd percentile (20% 49/244) of the study population) was 6
      times increased (RR=6.4; 95% confidence interval (CI) 1.46-28.52) after CrSpRT, 4
      times (RR=4.2; 95% CI 1.81-9.63) after Crth and 5 times (RR=51; 95% CI 2.23
      11.59) when irradiation was administered at the age of 8 years or younger. CrRT
      and CrSpRT and age at treatment are the main determinants of short stature in
      male and female childhood cancer survivors.

PMID- 11290437
TI  - Risk of a new primary cancer among patients with lung cancer of different
      histological types.
AB  - The risk of a new primary cancer (NPC) among 77548 Finnish lung cancer patients
      from 1953 to 1995 was analysed by the histological type of the lung cancer. The
      relative risks were expressed as standardised incidence ratios (SIR, ratio of the
      observed and expected numbers of cases). During the follow-up, 1148 NPCs were
      observed among men and 152 among women. After exclusion of lung cancers, the risk
      of NPC was elevated in both males (SIR 1.07; 95% confidence interval (CI) 1.00
      1.14) and females (SIR 1.21; 95% CI 1.02-1.42). The excess was larger among lung
      cancer patients with small-cell carcinoma and adenocarcinoma than those with
      squamous-cell carcinoma. In all major histological groups of lung cancer,
      significant excess risks were found for cancers of the larynx (SIRs 2.94-4.25),
      and bladder (SIRs 2.16-2.86). Significantly elevated SIRs were also found for
      cancers of the stomach (SIR 1.42; 95% CI 1.12-1.76) and kidney (SIR 2.18; 95% CI
      1.56-2.97) in squamous-cell carcinoma; for brain tumours (SIR 3.26; 95% CI 1.20
      7.09) in small-cell carcinoma; and for cancers of the prostate (SIR 1.68; 95% CI
      1.21-2.27) and thyroid (SIR 3.79; 95% CI 1.23-8.85), and brain tumours (SIR 2.34;
      95% CI 1.07-4.43) in adenocarcinoma. The risk of contracting NPC at sites where
      the majority of tumours are adenocarcinomas was elevated among patients with
      adenocarcinoma of the lung, but not among squamous-cell or small-cell carcinoma
      patients. In adenocarcinoma, the excess risks of several smoking-related cancers
      tended to be somewhat lower than those in the other two histological categories.
      The relative risk of a NPC among patients diagnosed with lung cancer in 1985-1995
      was higher than that of patients from earlier periods in all comparable follow-up
      categories (up to 10 years), possibly suggesting that the increased use of
      cytostatic drugs had increased the risk of NPC.

PMID- 11290438
TI  - A targeted cytotoxic somatostatin (SST) analogue, AN-238, inhibits the growth of
      H-69 small-cell lung carcinoma (SCLC) and H-157 non-SCLC in nude mice.
AB  - Recently, we developed a cytotoxic analogue of somatostatin (SST), AN-238, in
      which the SST carrier peptide RC-121 was linked to 2-pyrrolinodoxorubicin (2
      pyrrolino-DOX) (AN-201), a potent derivative of doxorubicin. AN-238 can be
      targeted to SST receptors (SSTRs) on tumours. In the present study, we evaluated
      the effects of AN-238 on the growth of H-69 small-cell lung carcinoma (SCLC) and
      H-157 non-SCLC xenografted into nude mice. High affinity binding sites for SST
      are present in H-69 SCLC and were now detected in H-157 non-SCLC xenografts, but
      not in H-157 cells. A strong expression of the human SSTR subtype 2 (hSSTR-2) and
      a weaker expression of subtype 5 (hSSTR-5) was found in H-69 SCLC cells, but not
      in H-157 non-SCLC cells. However, a strong expression of mRNA for mouse (m)SSTR-2
      could be detected in H-157 xenografts. AN-238 effectively inhibited the growth of
      H-69 SCLC tumours in nude mice. Twenty-six days after a single injection of AN
      238 at 200 nmol/kg, the volume of H-69 tumours was decreased by approximately 55%
      (P<0.05) compared with the controls, while AN-201 at the same dose was highly
      toxic and produced only a minor tumour inhibition. To evaluate the potency of
      multiple doses of AN-238, nude mice bearing H-69 SCLC received three injections
      of AN-238 at 150 nmol/kg on days 1, 12 and 28. In the period of 42 days after the
      first injection, the growth rate of H-69 tumours was approximately 50% lower than
      that of controls. In nude mice bearing H-157 non-SCLC tumours, a single i.v.
      administration of AN-238 at 200 nmol/kg inhibited tumour volume by 91% after 28
      days (P<0.01 compared with controls). AN-201 was toxic and ineffective at the
      same dose. Two injections of AN-238 at 150 nmol/kg given on days 1 and 18
      produced 83% inhibition of H-157 tumour growth (P<0.01 versus controls). AN-238
      given as a single dose of 200 nmol/kg induced necrosis, while two injections of
      150 nmol/kg induced apoptosis in the tumour tissue. Our results indicate that
      targeted cytotoxic SST analogue AN-238 could be considered for therapy of both
      SCLC and non-SCLC.

PMID- 11290439
TI  - Melanoma cells stimulate osteoclastogenesis, c-Src expression and osteoblast
      cytokines.
AB  - Malignant melanomas metastasise to the bone and enhance osteoclast bone
      resorption. We demonstrated that a 48-h-B16 melanoma cell conditioned media
      (B16CM) induced osteoclastogenesis in mouse bone marrow cultures, without the
      requirement of B16 cell-bone marrow cell co-culture. B16 cells transcriptionally
      expressed detectable levels of TGFbeta1, IL-6, M-CSF, GM-CSF and TNFalpha mRNAs,
      albeit to a lower extent compared with levels in osteoblasts, and failed to
      express PTHrP, OPGL, OPG and IL-1beta. Interestingly, B16CM greatly upregulated
      IL-1beta, IL-6 and GM-CSF, and modestly enhanced TNFalpha and OPGL mRNA
      expression in osteoblasts, suggesting a potential indirect stimulation of
      osteoclastogenesis via the osteogenic lineage. B16CM barely upregulated c-Fos,
      but strongly and time-dependently enhanced c-Src expression in the total bone
      marrow cultures during osteoclast differentiation. Moreover, c-Src expression was
      enhanced in differentiated and purified osteoclast preparations to higher levels
      than in stromal cells. In conclusion, melanoma induces osteoclast generation with
      a paracrine mechanism independent of cell-cell contact, specifically upregulating
      c-Src in osteoclasts and cytokine expression in osteoblasts.

PMID- 11290440
TI  - Effects of the luteinising hormone-releasing hormone (LH-RH) agonist leuprolide
      on adenylyl cyclase regulation through G-protein coupled receptors in rat ventral
      prostate.
AB  - Luteinising hormone-releasing hormone (LH-RH) agonists are widely used for the
      therapy of advanced prostate cancer through the suppression of testosterone
      secretion. Furthermore, recent studies indicate the existence of prostate LH-RH
      receptors coupled to signalling pathways resulting in direct antiproliferative
      effects. In order to shed light on the mechanisms through which these compounds
      inhibit prostate cell growth, we investigated the effects of leuprolide (a LH-RH
      agonist) treatment of rats compared with the effects of surgical castration on
      the behaviour of G-protein coupled receptors acting through adenylyl cyclase in
      the ventral prostate. Important decreases of both plasma testosterone levels and
      ventral prostate weight were observed 5 weeks after subcutaneous (s.c.) injection
      of a leuprolide-depot preparation (1.5 mg/kg body weight (b.w.)) or 5 days after
      bilateral gonadectomy. However, leuprolide treatment increased the number of
      vasoactive intestinal peptide (VIP) receptors and the ability of this
      neuropeptide to stimulate adenylyl cyclase activity in prostate membranes,
      whereas surgical castration decreased both parameters. Moreover, leuprolide
      resulted in significant increases of prostate alpha(s) and alpha(i1-3) (but not
      alpha(i1) and beta) G-protein levels, while the four G-protein subunits were
      overexpressed after gonadectomy. The estimation of alpha(s) and alpha(i) activity
      by experiments with Gpp[NH]p and forskolin indicated a potentiation of the two
      arms of adenylyl cyclase regulation in leuprolide-treated rats. Present
      observations suggest that leuprolide treatment leads to an antimitogenic response
      by acting mainly through the activation of Gi proteins negatively coupled to
      adenylyl cyclase.

PMID- 11290441
TI  - Effects of a novel trinuclear platinum complex in cisplatin-sensitive and
      cisplatin-resistant human ovarian cancer cell lines: interference with cell cycle
      progression and induction of apoptosis.
AB  - We evaluated the effects of the trinuclear platinum complex, BBR 3464, in a human
      ovarian carcinoma cell line (OAW42) and in its cisplatin (CDDP)-resistant
      counterpart (OAW42MER). A 14-fold increased sensitivity to a 1-h BBR 3464
      exposure was found in OAW42MER cells compared with their parental cell line. Flow
      cytometric experiments showed that BBR 3464 was able to induce a persistent block
      of OAW42 and OAW42MER cells in the G2M phase, whereas CDDP caused an initial
      accumulation of cells in the S phase followed by an increase in the G2M cell
      fraction in both cell lines. Exposure to equitoxic (IC(50)) drug concentrations
      induced programmed cell death in both cell lines. However, the percentage of
      cells with an apoptotic nuclear morphology was slightly higher after CDDP than
      BBR 3464 treatment in OAW42 cells, whereas the opposite pattern was observed in
      OAW42MER cells. Degradation of the nuclear lamin B was detected in OAW42 cells
      after exposure to each drug. Conversely, in OAW42MER cells lamin B cleavage was
      only appreciable after BBR 3464 exposure. In OAW42 cells, CDDP and BBR 3464 did
      not appreciably affect the mitochondrial membrane potential (Deltapsi(mt)),
      whereas in the OAW42MER cell line a marked Deltapsi(mt) reduction was observed
      after exposure to BBR 3464, but not to CDDP. The results of the study would
      suggest that the sensitivity to BBR 3464 observed in the CDDP-resistant OAW42MER
      cell line might be attributable to the ability of the trinuclear platinum complex
      to modify DNA in a way which is different from that of CDDP and, as a
      consequence, to induce different cellular responses to DNA damage such as the
      triggering of specific apoptotic pathways.

PMID- 11290442
TI  - Reversal of multidrug resistance and increase in plasma membrane fluidity in CHO
      cells with R-verapamil and bile salts.
AB  - Studies with multidrug resistance modifiers indicate that perturbations of the
      cell membrane structure may influence P-glycoprotein (P-gp)-mediated drug
      transport. We describe studies of plasma membrane order using electron
      paramagnetic resonance (EPR) in resistant (CH(R)C5) and sensitive (AUXB1) chinese
      hamster ovary cells treated with R-verapamil and bile salts. Cell growth rates
      were determined in presence of doxorubicin mitomycin and cisplatin. The plasma
      membrane order in untreated resistant cells was higher than in the sensitive
      cells. Both the bile salt taurochenodeoxycholate (TCDC; 0.2-1.6 mM) and R
      verapamil (1-3 microM) lowered the membrane order in the CH(R)C5 cells to that in
      the sensitive cells and reversed the resistance to doxorubicin and mitomycin. The
      bile salt tauroursodeoxycholate (TUDC; 0.2-3 mM) did not lower membrane order and
      did not sensitise CH(R)C5 cells. Neither R-verapamil, TCDC nor TUDC reduced the
      membrane order of the sensitive cells AUXB1 cells. These results support the view
      that changes in multidrug resistance in Chinese hamster ovary cells and P-gp
      function are associated with alterations in the fluidity of the plasma membrane.

PMID- 11290443
TI  - Cryptobiosis--a peculiar state of biological organization.
AB  - David Keilin (Proc. Roy. Soc. Lond. B, 150, 1959, 149-191) coined the term
      'cryptobiosis' (hidden life) and defined it as 'the state of an organism when it
      shows no visible signs of life and when its metabolic activity becomes hardly
      measurable, or comes reversibly to a standstill.' I consider selected aspects of
      the 300 year history of research on this unusual state of biological
      organization. Cryptobiosis is peculiar in the sense that organisms capable of
      achieving it exhibit characteristics that differ dramatically from those of
      living ones, yet they are not dead either, so one may propose that cryptobiosis
      is a unique state of biological organization. I focus chiefly on animal
      anhydrobiosis, achieved by the reversible loss of almost all the organism's
      water. The adaptive biochemical and biophysical mechanisms allowing this to take
      place involve the participation of large concentrations of polyhydroxy compounds,
      chiefly the disaccharides trehalose or sucrose. Stress (heat shock) proteins
      might also be involved, although the details are poorly understood and seem to be
      organism-specific. Whether the removal of molecular oxygen (anoxybiosis) results
      in the reversible cessation of metabolism in adapted organisms is considered,
      with the result being 'yes and no', depending on how one defines metabolism.
      Basic research on cryptobiosis has resulted in unpredicted applications that are
      of substantial benefit to the human condition and a few of these are described
      briefly.

PMID- 11290444
TI  - Tetranectin-like protein in vertebrate serum: a comparative immunochemical
      analysis.
AB  - The glycoprotein tetranectin (TN) found in human serum is a 90-kDa homotrimeric C
      type lectin binding Ca2+, heparin and plasminogen kringle 4. TN is suggested as
      being implicated in tissue remodelling. The antigenic reactivity of putative TN
      was examined in serum from 14 different animal species using three sandwich
      enzyme immunoassays for human TN. Crab-eating macaque serum showed the strongest
      reaction, followed by horse and cat. Serum from cow, goat, pig, mouse and chicken
      reacted weakly, while dog, trout, and the amphibian and the reptile species did
      not react. The TN-like protein from macaque, horse and cat serum bound heparin
      and showed the same dependence on Ca2+ for interaction with the monoclonal
      antibodies as human TN. Gel filtration of sera from the three animal species
      showed that the TN-like protein eluted as single peaks with a M(r) of 70-90 kDa.
      Western blotting of horse and cat TN-like protein electrophoresed under reducing
      conditions showed that the antibodies against human TN reacted with a single band
      with an approximate M(r) of 30 kDa, indicating that the TN-like protein is also a
      homotrimer. Horse and cat TN-like protein interacted with human kringle 4
      sepharose. Most likely, the reacting protein represents crab-eating macaque,
      horse and cat homologues of human TN.

PMID- 11290446
TI  - Discovery of novel trimethylalkanes in the internal hydrocarbons of developing
      pupae of Heliothis virescens and Helicoverpa zea.
AB  - Novel trimethyl-branched alkanes which eluted with the monomethylalkanes were
      identified in the internal lipids of Helicoverpa zea but were not present in
      Heliothis virescens. Their structures were unique in that the first methyl branch
      occurred on carbon 2 and the 2nd and 3rd methyl branch points were separated by a
      single methylene. Novel trimethylalkanes identified from their chemical
      ionization and electron impact mass spectra were 2,18,20
      trimethyltetratriacontane, 2,18,20-trimethylhexatriacontane, and 2,24,26
      trimethyldotetracontane. Previous reports did not find these trimethylalkanes in
      the cuticular surface lipids of larvae, pupae or adults of either species. The
      internal pupal hydrocarbons of H. virescens and H. zea amounted to 123 microg and
      304 microg per pupa, respectively. They consisted of n-alkanes (8 and 4%,
      respectively) and methyl-branched alkanes (88 and 94%, respectively). The n
      alkanes ranged in chain length from approximately 21 to 35 carbons and the methyl
      branched alkanes from approximately 26 to 55 carbons vs. methyl-branched alkanes
      from 28 to 37 carbons previously reported for hydrocarbons from the pupal
      cuticular surface. The major n-alkane was heptacosane (3.3 and 1.2%,
      respectively, in H. virescens and H. zea). The major methyl-branched alkanes in
      H. virescens were methylhentriacontane (15%), methyltritriacontane (12%) and
      dimethyltritriacontane (10%), and in H. zea were methylnonacosane (17%),
      dimethylnonacosane (9%) and methylhentriacontane (20%). Except for the novel
      trimethylalkanes, the methylalkane branch points were predominantly on odd
      numbered carbons as has been reported for these and other species.

PMID- 11290445
TI  - Expression of apoptosis-related proteins in involuting mammary gland of sow.
AB  - The expression of apoptosis-related proteins: TGF-beta1 (local inductor), TGF
      beta-receptor, Bax (promoter), Bcl-2 (inhibitor) and CPP-32 (executor of
      apoptosis); the subcellular distribution of Bax; as well as the number and
      morphology of apoptotic cells in low-, moderate-, and high-involuted mammary
      glands of sow (four to six days after weaning) were investigated. The
      immunohistochemical study demonstrated a statistically significant increase in
      the integrated optical density (IOD) of lobuloalveolar mammary tissue labelling
      with anti-Bax antibody from low- through moderate-, to high-involuted glands. The
      immunoelectron microscopy revealed that Bax was localised in the cytosol, on the
      membranes of mitochondrium and rough endoplasmic reticulum, in nuclear envelope
      pores, and over heterochromatin of mammary epithelial cells. The increase in
      Bax/Bcl-2 ratio (2.3, 2.6 and 5.6 for low-, moderate-, and high-involuted glands,
      respectively) indicated the increasing susceptibility of mammary epithelial cells
      to apoptosis in the course of involution. The highest Bax/Bcl-2 ratio in high
      involuted glands coincided with the highest expression of CPP-32 (caspase 3), TGF
      beta1 and TGF-beta1 receptor. The number of apoptotic cells (simultaneous TUNEL
      and Hoechst 33342 staining) was 2.7, 3.4 and 3.8% for low-, moderate-, and high
      involuted glands, respectively. The ultrastructural evaluation showed
      characteristic morphological features of apoptosis such as: margination and
      condensation of chromatin; pyknosis and fragmentation of the nucleus; and
      formation of apoptotic bodies. Phagocytosis of apoptotic cells by macrophages was
      also documented. The results of the present study suggest the involvement of
      Bax/Bcl-2 check-point in the regulation, CPP-32 in the execution, but TGF-beta1
      in the induction of apoptosis of mammary epithelial cells in the involuting
      mammary gland of sow.

PMID- 11290447
TI  - Lipid fatty acid and protein pattern of equine prostasome-like vesicles.
AB  - The semen of several mammals contains vesicles of different composition and
      origin. We have recently reported on the presence of lipoprotein vesicles in
      stallion semen. To a certain extent, these resemble human prostasomes, but differ
      from them in amount and composition. These horse-semen prostasome-like vesicles
      may be important, not only in horse reproductive physiology, but also in view of
      stallion semen cryopreservation. In this paper, we have studied horse-semen
      prostasome-like vesicles and found that they possess less saturated fatty acid
      than human prostasomes. Moreover, their protein pattern (SDS-PAGE
      electrophoresis) shows that the 30-50-kDa fraction is less abundant in stallion
      vesicles. In addition, fluidity (measured as fluorescence anisotropy of
      diphenylhexatriene) is higher in horse prostasome-like vesicles than in human
      prostasomes, albeit being much lower than that of most membranes. These findings
      may be connected to some species-related differences in reproductive physiology:
      the vaginal milieu of the mare is not acidic and the deposition of semen is
      intrauterine in the horse but vaginal in humans.

PMID- 11290448
TI  - Cellular uptake of taurine by lactating porcine mammary tissue.
AB  - Milk taurine plays a critical role in neonatal development. Taurine uptake in
      lactating sow mammary tissue has not been characterized previously. The kinetic
      properties, ion dependence and substrate specificity of taurine uptake were
      characterized in mammary tissue collected from lactating sows at slaughter.
      Tissue explants were incubated in an isosmotic physiologic buffer with
      [3H]taurine tracer to measure taurine uptake. Taurine uptake was dependent upon
      the presence of extracellular sodium and chloride ions, which is consistent with
      the co-transport of sodium and chloride with taurine. Uptake was not dependent
      upon ion exchange mechanisms or upon furosemide-sensitive ion co-transport.
      Taurine uptake was saturable and exhibited an apparent Km of 20 microM and a
      V(max) of 386 micromol/kg cell water/30 min. Substrate specificity studies
      indicated a strong interaction of beta-amino acids with the taurine transport
      system. Taurine transport in lactating sow mammary tissue is therefore a high
      affinity, sodium-dependent mechanism specific for beta-amino acids, and is
      analogous to sodium-dependent taurine uptake in other tissues. The high affinity
      and high specificity of the taurine uptake system allows for concentration of
      taurine within the mammary cell and is ultimately responsible for provision of
      taurine required for neonatal development.

PMID- 11290449
TI  - Characterization of gastrointestinal chitinase in the lizard Sceloporus undulatus
      garmani (Reptilia: Phrynosomatidae).
AB  - Most studies on chitinase activity in lizards have been concerned with
      Palaearctic (European) and Laurasian (Middle Eastern and Asian) taxa. Several
      genera of Old World lizards, Anguis, Uromastix, Chamaeleo and Lacerta, have been
      shown to possess chitinolytic activity. To date, only one New World lizard,
      Anolis carolinensis, has been reported to exhibit chitinolytic activity. In the
      present study, chitinase activity was characterized in a second New World taxon,
      Sceloporus undulatus garmani, a New World, phrynosomatid lizard. Chitinolytic
      activity was measured by incubating tissue extracts with a radioactive chitin
      substrate, acetyl-[H3]chitin and determining acid soluble radioactivity as an
      estimate for chitin hydrolysis. Chitinolytic activity was present in stomach,
      small intestine and pancreas extracts, with the stomach and pancreas having the
      highest specific activities. Chitinolytic activity was higher at pH 4.5 than at
      pH 7.5. The stomach chitinase is immunologically similar to the gastric chitinase
      previously described for rainbow trout. Western blot analysis showed anti
      chitinase cross-reactivity in the extracts of the stomach, but no cross
      reactivity in the pancreatic or intestinal extracts, suggesting different
      isoforms of chitinase. There was no detected lysozyme activity (less than 0.01
      mg/ml lysozyme) present in the extracts of the stomach, small intestine and
      pancreas. The localization of chitinolytic activity in S. u. garmani is in
      agreement with earlier reptilian reports on the distribution of chitinase.

PMID- 11290450
TI  - Glycosidase activity in the post-ecdysial cuticle of the blue crab, Callinectes
      sapidus.
AB  - We have previously demonstrated a marked change in sugar moieties of
      glycoproteins of the cuticle of the blue crab, Callinectes sapidus, between 0.5
      and 3 h post-ecdysis. The present study has identified a glycosidase that appears
      in the cuticle during the early post-ecdysial hours. The enzyme has affinities
      for p-nitrophenyl derivatives of both N-acetylglucosamine and N
      acetylgalactosamine. Both activities are competitively inhibited by chitobiose,
      suggesting that the enzyme could be a N-acetylhexosaminidase (EC 3.2.1.52).
      Atypical of N-acetylhexosaminidases described to date, this enzyme has a pH
      optimum of 7.0. The enzyme activity is high during the post-ecdysial period
      coincident with the changes in glycoprotein profiles observed in vivo. Partial
      purification of the enzyme has been accomplished by Sephacryl size-exclusion
      chromatography followed by concanavalin A affinity chromatography.

PMID- 11290451
TI  - Effects of exogenous N-acetylhexosaminidase on the structure and mineralization
      of the post-ecdysial exoskeleton of the blue crab, Callinectes sapidus.
AB  - A cuticular glycosidase with characteristics of N-acetyl-beta-D-hexosaminidase
      (HexNAcase) was identified in post-ecdysial crab cuticle. Its appearance
      coincided with changes in cuticular glycoproteins and the onset of
      mineralization. To test if HexNAcase might be the causative agent in the
      alteration of the glycans and initiation of calcification, newly molted crab
      cuticle was treated with exogenous HexNAcase. Treating cuticular extracts from
      crabs at 0 h post-ecdysis with exogenous HexNAcase mimicked those changes
      observed in vivo. Specifically, the enzyme decreased the concanavalin A affinity
      of an 83-kDa glycoprotein that binds to calcite crystals in vitro. Treating
      pieces of 0 h post-ecdysial cuticle with HexNAcase rendered them capable of
      nucleating calcite in vitro (similar to 5 h post-ecdysial cuticle), while
      untreated, 0 h controls remained uncalcified. The data imply a role of the
      cuticular HexNAcase-like enzyme in the initiation of calcite nucleation in the
      newly formed exoskeleton.

PMID- 11290452
TI  - A common class of nematode glutathione S-transferase (GST) revealed by the
      theoretical proteome of the model organism Caenorhabditis elegans.
AB  - The genome verified C. elegans free-living nematode model is a new tool for
      investigating gene expression in human and animal nematode parasites. There is
      limited information on designating glutathione S-transferase (GST) to specific
      classes in lower invertebrates such as nematodes. Following cloning, amino acid
      sequence alignment, recombinant expression and Western blotting we provide
      evidence of a new GST class in nematodes or lower invertebrates.

PMID- 11290453
TI  - Protein purification, cDNA cloning and gene expression of lysozyme from eri
      silkworm, Samia cynthia ricini.
AB  - Lysozyme was isolated from immunized hemolymph of Samia cynthia ricini larvae by
      heat treatment, cation exchange and reverse-phase chromatography. A cDNA encoding
      lysozyme was cloned by screening the cDNA library from immunized fat body using,
      as a probe, a DNA fragment obtained by PCR-based differential display method. The
      deduced amino acid sequence showed high homology with other chicken-type
      lysozymes. The calculated molecular mass of the mature peptide was 13785, which
      agreed precisely with that obtained by MALDI-TOF mass spectrometry of the
      isolated protein. The lysozyme transcripts were detected at a significant level
      in naive fat body, and the level increased 5-10-fold upon injection of the larvae
      with UV-killed bacteria or peptidoglycan.

PMID- 11290454
TI  - Lipid and fatty acid composition of canine lipoproteins.
AB  - Lipid classes and their fatty acids were studied in the major lipoprotein
      fractions from canine, in comparison with human, plasma. In dogs, high-density
      lipoprotein (HDL), the main carrier of plasma phospholipid (PL), cholesterol
      ester (CE) and free cholesterol, was the most abundant lipoprotein, followed by
      low and very-low density lipoproteins (LDL and VLDL). Notably, LDL and VLDL
      contributed similarly to the total dog plasma triacylglycerol (TG). The PL
      composition was similar in all three lipoproteins, dominated by
      phosphatidylcholine (PC). Even though the content and composition of lipids
      within and among lipoproteins differed markedly between dog and man, the total
      amount of circulating lipid was similar. All canine lipoproteins were relatively
      richer than those from humans in long-chain (C20-C22) n-6 and n-3 polyunsaturated
      fatty acids (PUFA) but had comparable proportions of total saturated and
      monoenoic fatty acids, with 18:2n-6 being the main PUFA in both mammals. The
      fatty acid profile of canine and human lipoproteins differed because they had
      distinct proportions of their major lipids. There were more n-3 and n-6 long
      chain PUFA in canine than in human plasma, because dogs had more HDL, their HDL
      had more PC and CE, and both these lipids were richer in such PUFA.

PMID- 11290455
TI  - ATP and ADP hydrolysis in fish, chicken and rat synaptosomes.
AB  - Ecto-enzymes capable of hydrolyzing ATP and ADP (NTPDase) are present in the
      central nervous system of various species. In the present investigation we
      studied the synaptosomal NTPDase (ATP diphosphohydrolase, apyrase, E.C. 3.6.1.5)
      from fish, chicken and rats under different conditions and in the presence of
      several classical inhibitors. The cation concentration required for maximal
      activity was 0.5 mM for fish, 1.0 mM for chickens and 1.5 mM for rats with both
      substrates. The results showed that the pH optimum for all animal preparations
      was close to 8.0. The temperature used was 25-27 degrees C for fish and 35-37
      degrees C for chicken and rat preparations. The inhibitors azide and fluoride
      only inhibited the preparation at high concentrations (10 mM). Lanthanum (0.1-0.4
      mM), N-ethylmaleimide (0.4-3.0 mM) and ouabain (0.5-3.0 mM) had no effect on
      NTPDase activity from fish, chickens or rats. Orthovanadate (0.1-0.3 mM) only
      inhibited fish synaptosomal NTPDase. Trifluoperazine (0.05-0.2 mM) and suramin
      (0.03-0.3 mM) inhibited NTPDase at all concentrations tested. Suramin was the
      most potent compound in causing inhibition, presenting inhibition at 30 microM.
      Our results demonstrate that the synaptosomal NTPDase response to several factors
      is similar in fish, chickens and rats, and that the enzyme presents functional
      homology.

PMID- 11290456
TI  - Carotenoid discrimination by the avian embryo: a lesson from wild birds.
AB  - The concentrations (microg/g wet yolk) of total carotenoids in eggs of the common
      moorhen (Gallinula chloropus), American coot (Fulica americana) and lesser black
      backed gull (Larus fuscus), collected in the wild, were 47.5, 131.0 and 71.6,
      respectively. In contrast to data for eggs of the domestic chicken, beta-carotene
      was a significant component in the yolks of these three wild species, forming 25
      29% by wt. of the total carotenoids present. The concentration of total
      carotenoids in the livers of the newly-hatched chicks was 5-10 times higher than
      in the other tissues and beta-carotene was again a major component, forming 37
      58% of the hepatic carotenoids. In the newly-hatched gull, the proportions of
      both lutein and zeaxanthin were very low in the liver but high in the heart and
      muscle when compared with the yolk. By contrast canthaxanthin, echinenone and
      beta-carotene were very minor constituents of heart and muscle when compared with
      their proportions in the yolk of the gull. The proportions of lutein and
      zeaxanthin in the liver of the newly-hatched coot and moorhen were also far lower
      than in the yolk whereas the liver was relatively enriched with beta
      cryptoxanthin, beta-carotene and (in the moorhen) echinenone. The results
      indicate that avian embryos discriminate between different carotenoids during
      their distribution from the yolk to the various tissues.

PMID- 11290457
TI  - Purification, N-terminal amino acid sequence, and some properties of Cu, Zn
      superoxide dismutase from Japanese flounder (Paralichthys olivaceus) hepato
      pancreas.
AB  - Cu, Zn-superoxide dismutase (SOD) has been purified to homogeneity from Japanese
      flounder Paralichthys olivaceus hepato-pancreas. The purification of the enzyme
      was carried out by an ethanol/chloroform treatment and acetone precipitation, and
      then followed by column chromatographies on Q-Sepharose, S-Sepharose and Ultrogel
      AcA 54. On SDS-PAGE, the purified enzyme gave a single protein band with
      molecular mass of 17.8 kDa under reducing conditions, and showed approximately
      equal proportions of 17.8 and 36 kDa molecular mass under non-reducing
      conditions. Three bands were obtained when the purified enzyme was subjected to
      native-PAGE, both on protein and activity staining, but the electrophoretic
      mobility of the purified enzyme differed from that of bovine erythrocyte Cu, Zn
      SOD. Isoelectric point values of 5.9, 6.0 and 6.2, respectively, were obtained
      for the three components. The N-terminal amino acid sequence of the purified
      enzyme was determined for 25 amino acid residues, and the sequence was compared
      with other Cu, Zn-SODs. The N-terminal alanine residue was unacetylated, as in
      the case of swordfish SOD. Above 60 degrees C, the thermostability of the enzyme
      was much lower than that of bovine Cu, Zn-SOD.

PMID- 11290458
TI  - In vivo and in vitro effects of prolactin and growth hormone on lipid metabolism
      in a teleost, Anabas testudineus (Bloch).
AB  - Prolactin (PRL) has an important role in the regulation of water and electrolyte
      homeostasis in teleosts. The present study was designed to evaluate the role of
      PRL and GH on malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH) and
      isocitrate dehydrogenase (ICDH) in Anabas testudineus. Ovine prolactin
      significantly inhibited ME, G6PDH and ICDH activities when administered in vivo
      compared to vehicle treated controls. In vivo administration of PRL reversed the
      action of bromocryptine on enzyme activities. Ovine growth hormone in vivo also
      modified the effect of bromocryptine but not to the level of prolactin. Combined
      action of PRL+GH in vivo was most effective in keeping the enzyme activities at
      normal level after bromocryptine treatment. Prolactin in vitro also reversed the
      action of bromocryptine on enzyme activities, while GH in vitro failed to do so.
      Hence, prolactin seems to have an inhibitory effect on lipid metabolism in this
      teleost. Combined action of PRL+GH is more prominent in in vivo conditions at low
      PRL levels. Dopaminergic pathways may be involved in the control of prolactin and
      to some extent on growth hormone secretion.

PMID- 11290459
TI  - Pernin: a novel, self-aggregating haemolymph protein from the New Zealand green
      lipped mussel, Perna canaliculus (Bivalvia: Mytilidae).
AB  - A protein, designated pernin, found in the New Zealand green-lipped mussel,
      comprises almost all of the protein in cell-free haemolymph. It occurs as large,
      aggregate structures of several hundred units resembling small virus-like
      particles. Pernin is a non-pigmented, glycosylated protein, composed of 497 amino
      acids, which has an estimated molecular mass of 60 kDa. It is exceptionally rich
      in histidine (13.7%) and aspartic acid (12.3%), amino acids both known to
      participate in the binding of divalent metal cations. In addition, pernin has
      serine protease inhibitor activity, likely due to a sequence of eight N-terminal
      amino acid residues, separated from the remainder of the protein via a histidine
      aspartate spacer. The pernin monomer comprises three regions of obvious sequence
      duplication. These make up approximately 95% of the pernin molecule and have
      sequences clearly homologous to the active-site domain of Cu-Zn SODs (superoxide
      dismutases). Despite several of the metal ion co-ordinating histidine residues
      being retained, pernin contains no Cu or Zn. It is, however, associated with Fe
      with an apparent stoichiometry of 1 atom of Fe to 6 molecules of pernin. Since
      pernin has no demonstrable SOD activity, these SOD-derived sequences presumably
      have been modified for another function.

PMID- 11290460
TI  - Dynamic changes in mouse lipoproteins induced by transiently expressed human
      phospholipid transfer protein (PLTP): importance of PLTP in prebeta-HDL
      generation.
AB  - The plasma phospholipid transfer protein (PLTP) plays an important role in the
      regulation of plasma high density lipoprotein (HDL) levels and governs the
      distribution of HDL sub-populations. In the present study, adenovirus mediated
      overexpression of human PLTP in mice was employed to investigate the distribution
      of PLTP in serum and its effect on plasma lipoproteins. Gel filtration
      experiments showed that the distributions of PLTP activity and mass in serum are
      different, suggesting that human PLTP circulated in mouse plasma as two distinct
      forms, one with high and the other with low specific activity. Our study further
      demonstrates that overexpression of PLTP leads to depletion of HDL and that, as
      PLTP activity declines, replenishment of the HDL fraction occurs. During this
      process, the lipoprotein profile displays transient particle populations,
      including apoA-IV and apoE-rich particles in the LDL size range and small
      particles containing apoA-II only. The possible role of these particles in HDL
      reassembly is discussed. The increased PLTP activity enhanced the ability of
      mouse sera to produce pre(beta)-HDL. The present results provide novel evidence
      that PLTP is an important regulator of HDL metabolism and plays a central role in
      the reverse cholesterol transport (RCT) process.

PMID- 11290461
TI  - Seasonal changes in adrenal and gonadal activity in the quail, Perdicula
      asiatica: involvement of the pineal gland.
AB  - The present study assessed annual adrenal gland activity in the Indian tropical
      Jungle bush quail, Perdicula asiatica. We also elucidated the role of the annual
      variations in gonadal steroids and melatonin in the regulation of its activity.
      Increasing day length (photoperiod), ambient temperature and rainfall are
      positively correlated with adrenal and gonadal functions, and inversely related
      to pineal gland activity. Pineal, adrenal and gonadal weights showed cyclical
      patterns relative to environmental factors, which were also correlated with
      plasma melatonin, corticosterone and gonadal steroids, respectively. In both
      sexes of P. asiatica, pineal gland weight and/or plasma melatonin levels were
      inversely related to adrenal lipids, (e.g. phospholipids, free and esterified
      cholesterol) and plasma corticosterone levels. Melatonin levels also showed an
      inverse relationship with plasma testosterone and estradiol levels. These studies
      indicate that changes in environmental factors promote annual variations in
      adrenal and gonadal activity probably by modulating the pineal gland. Melatonin
      receptors have been localized in the pars tuberalis, adrenal gland and gonads of
      birds, the pineal gland may, therefore, mediate environmental stimuli indirectly
      and directly to down regulate adrenal and gonadal activity, which run in parallel
      in this species.

PMID- 11290462
TI  - Neuroimaging and cartography: mapping brain tumors.

PMID- 11290463
TI  - MRS imaging of gamma knife treatment for gliomas: from metabolite ratios to
      therapeutic rationale.

PMID- 11290464
TI  - The four Ps of acute stroke imaging: parenchyma, pipes, perfusion, and penumbra.

PMID- 11290465
TI  - Enhancing our understanding of multiple sclerosis: tracking contrast-enhancing
      plaques with MR imaging.

PMID- 11290466
TI  - Preoperative proton MR spectroscopic imaging of brain tumors: correlation with
      histopathologic analysis of resection specimens.
AB  - BACKGROUND AND PURPOSE: Tumor progression is often difficult to distinguish from
      nonneoplastic treatment response on the basis of MR images alone. This study
      correlates metabolite levels measured by preoperative MR spectroscopic (MRS)
      imaging with histologic findings of biopsies, obtained during image-guided
      resections of brain mass lesions, to clarify the potential role of MRS in making
      this distinction. METHODS: Twenty-nine patients with brain tumors underwent high
      resolution (0.2-1 cc) 3D proton MRS imaging and MR imaging before undergoing
      surgery; 11 had a newly diagnosed neoplasm, and 18 had recurrent disease.
      Surgical biopsies were obtained from locations referenced on MR images by
      guidance with a surgical navigation system. MR spectral voxels were
      retrospectively centered on each of 79 biopsy locations, and metabolite levels
      were correlated with histologic examination of each specimen. RESULTS: All mass
      lesions studied, whether attributable to tumor or noncancerous effects of
      previous therapy, showed abnormal MR spectra compared with normal parenchyma.
      When the pattern of MRS metabolites consisted of abnormally increased choline and
      decreased N-acetyl aspartate (NAA) resonances, histologic findings of the biopsy
      specimen invariably was positive for tumor. When choline and NAA resonances were
      below the normal range, histologic findings were variable, ranging from radiation
      necrosis, astrogliosis, and macrophage infiltration to mixed tissues that
      contained some low-, intermediate-, and high-grade tumor. CONCLUSION: This study
      demonstrated that 3D MRS imaging can identify regions of viable cancer, which may
      be valuable for guiding surgical biopsies and focal therapy. Regions manifesting
      abnormal MR spectra had a mixture of histologic findings, including astrogliosis,
      necrosis, and neoplasm.

PMID- 11290467
TI  - Serial proton MR spectroscopic imaging of recurrent malignant gliomas after gamma
      knife radiosurgery.
AB  - BACKGROUND AND PURPOSE: The diagnosis of brain tumors after high-dose radiation
      therapy is frequently limited by the lack of metabolic discrimination available
      with conventional imaging methods. The purpose of this study was to use proton MR
      spectroscopy to investigate serial changes in recurrent malignant gliomas after
      gamma knife radiosurgery to characterize tissue response to high-dose radiation.
      METHODS: Eighteen patients with recurrent gliomas were studied with MR imaging
      and 3D proton MR spectroscopic imaging at the time of radiosurgery and at regular
      time points thereafter. Choline (Cho) and N-acetyl aspartate levels were
      calculated on a voxel-by-voxel basis and compared with levels found in normal
      tissue and with levels observed at previous time points. The results of the
      spectral analysis were then compared with the radiologic findings. Statistical
      comparisons were precluded by the small sample sizes involved. RESULTS: Response
      within the gamma knife target was observed as a reduction of Cho levels and an
      increase in lactate/lipid levels, typically within 6 months of treatment.
      Increases in Cho correlated with poor radiologic response and suggested tumor
      recurrence, confirmed histologically in six cases. The development of a spectral
      abnormality preceded a coincident increase in contrast enhancement by 1 to 2
      months in nine cases. CONCLUSION: Proton MR spectroscopic imaging provided
      diagnostic and monitoring information before and after radiosurgery. Evaluation
      of metabolic changes with proton MR spectroscopy and structural changes with MR
      imaging improved tissue discrimination and provided correlation with histologic
      findings.

PMID- 11290468
TI  - Lateralizing ability of single-voxel proton mr spectroscopy in hippocampal
      sclerosis: comparison with mr imaging and positron emission tomography.
AB  - BACKGROUND AND PURPOSE: Proton MR spectroscopy (MRS) is still in the early stages
      in the evaluation of epilepsy, and comparisons with MR imaging and positron
      emission tomography (PET) in the same patients have rarely been documented. The
      purpose of this study was to evaluate the lateralizing ability of single-voxel
      MRS in comparison with MR imaging and PET in patients with hippocampal sclerosis.
      METHODS: Thirty-three patients with intractable temporal lobe epilepsy whose MR
      imaging diagnosis was unilateral hippocampal sclerosis and who underwent anterior
      temporal lobectomy and had good postsurgical outcome over 1-year follow-up were
      included in the study. MR spectra were obtained from the hippocampus bilaterally,
      using the point-resolved spectroscopy sequence. Metabolite ratios of NAA/Cho and
      NAA/Cr were calculated from the relative peak height measurements. An NAA/Cho
      ratio of 0.8 or less and an NAA/Cr ratio of 1.0 or less were regarded as
      abnormal. The MRS results were compared retrospectively with those of MR imaging
      and PET as to the ability to lateralize the epileptogenic focus. RESULTS: The
      sensitivity of MRS and PET (concordance with MR imaging) was 85% each in the
      lateralization of the ipsilateral lesion side. Bilateral abnormalities were seen
      in 30% of the patients. False-lateralization rates for MRS and PET were 3% and
      6%, respectively. The concordance rate of MRS and PET was 73%, when comparing the
      results of the ipsilateral lesion side. CONCLUSION: MRS may be used as an adjunct
      tool in the evaluation of hippocampal sclerosis, like PET, although its
      sensitivity has to be improved and the clinical significance of bilateral
      abnormality is still to be determined.

PMID- 11290469
TI  - Arterial hyperintensity on fast fluid-attenuated inversion recovery images: a
      subtle finding for hyperacute stroke undetected by diffusion-weighted MR imaging.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging is generally acknowledged
      to be more sensitive in detecting acute stroke than is conventional MR imaging.
      Our purpose in the present study was to evaluate the utility of fast fluid
      attenuated inversion recovery (FLAIR) MR imaging compared with that of diffusion
      weighted MR imaging for the diagnosis of hyperacute stroke. METHODS: We reviewed
      patient records and cerebral MR images from all patients in a 13-month period
      from whom diffusion-weighted and fast-FLAIR imaging were obtained within 6 hours
      after symptom onset (n = 11). Special attention was paid to the presence or
      absence of arterial hyperintensity on FLAIR images and abnormally high-signal
      regions on diffusion-weighted images in the affected vascular territories.
      RESULTS: Arterial hyperintensity was found in eight of 11 patients, all of whom
      had embolic or thrombotic infarctions with middle cerebral arterial (MCA)
      distribution. Arterial hyperintensity was negative in the remaining three
      patients; the vascular territories were the posterior circulation region in two
      of these patients and the MCA region in one, and the types of infarction in these
      same patients were lacunar in two and embolic in one. Regions with high-signal
      diffusion abnormalities relevant to the patients' symptoms were found in 10 of 11
      patients. One patient showed no diffusion abnormalities but the presence of
      arterial hyperintensity in the affected MCA territory on the initial MR
      examination, and manifested embolic infarction along with arterial hyperintensity
      on the initial FLAIR image. CONCLUSION: Although diffusion-weighted MR imaging is
      highly sensitive to stroke, diffusion-weighted MR imaging alone may not rule out
      a possible infarction. Arterial hyperintensity on FLAIR images can precede
      diffusion abnormalities and may provide a clue to the early detection of
      impending infarction.

PMID- 11290470
TI  - Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted
      signal intensity of acute stroke.
AB  - BACKGROUND AND PURPOSE: Serial study of such MR parameters as diffusion-weighted
      imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated
      inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information
      on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to
      establish the natural evolution of MR signal intensity characteristics of acute
      ischemic lesions and to assess the potential of using specific MR parameters to
      estimate lesion age. METHODS: Five serial echo-planar DWI studies with and
      without an inversion recovery pulse were performed in 27 patients with acute
      stroke. The following lesion characteristics were studied: 1) conventional ADC
      (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted
      signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)). RESULTS:
      The lesion ADC(CONV) gradually increased from low values during the first week to
      pseudonormal during the second week to supranormal thereafter. The lesion
      ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A
      low ADC value indicated, with good sensitivity (88%) and specificity (90%), that
      a lesion was less than 10 days old. All signal intensities remained high
      throughout follow-up. SI(DWI) showed no significant change during the first week
      but decreased thereafter. SI(T2) initially increased, decreased slightly during
      week 2, and again increased after 14 days. SI(FLAIR) showed the same initial
      increase as the SI(T2) but remained relatively stable thereafter. CONCLUSION: Our
      findings further clarify the time course of stroke evolution on MR parameters and
      indicate that the ADC map may be useful for estimating lesion age. Application of
      an inversion recovery pulse results in lower, potentially more accurate, absolute
      ADC values.

PMID- 11290472
TI  - Assessment of silent embolism from carotid endarterectomy by use of diffusion
      weighted imaging: work in progress.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler studies have suggested that
      microemboli are released into the arterial circulation during the majority of
      carotid endarterectomy (CEA) procedures. This, together with the observation that
      neuropsychological performance may decline postoperatively, has led to concern
      that cerebral infarction may occur unrecognized during CEA. Our objective was to
      examine this risk with diffusion-weighted imaging, a technique that is highly
      sensitive to acute cerebral infarction. METHODS: Eighteen participants (median
      age, 68 years; age range, 56-87 years) were assessed with diffusion-weighted
      imaging and the National Institutes of Health Stroke Scale before and after CEA.
      Imaging was performed using single-shot echo-planar imaging with a maximum
      diffusion sensitivity of b = 1000 s/mm(2) applied to three orthogonal planes.
      Preoperative imaging was performed a median of 2.5 hours before surgery (range,
      0.5-12.5 hours) and 15 hours after surgery (range, 1.5-58.5 hours). Two
      neuroradiologists independently interpreted the diffusion-weighted images,
      blinded to operative status and clinical findings. RESULTS: There was no
      diffusion-weighted imaging evidence of silent embolism in this series of 18
      participants (95% confidence interval limits, 0 to 10%). Clinical complications
      were confined to one case of confusion occurring after CEA; the diffusion
      weighted imaging results were normal in this case. CONCLUSION: There is no
      evidence from our series that silent cerebral infarction is a common occurrence
      during CEA. These data provide further support for the safety of CEA.

PMID- 11290471
TI  - Detection of clinically silent infarcts after carotid endarterectomy by use of
      diffusion-weighted imaging.
AB  - BACKGROUND AND PURPOSE: Intraprocedural transcranial Doppler sonography has
      identified multiple microembolic events during and immediately after carotid
      endarterectomy (CEA) or angioplasty, yet the rate of clinically evident stroke is
      small. To determine the significance of the transcranial Doppler sonography
      findings, we examined patients by use of diffusion-weighted imaging and fluid
      attenuated inversion recovery MR imaging before and immediately after CEA for
      evidence of clinically silent ischemic events. METHODS: Twenty-five patients with
      atherosclerotic disease of the carotid arteries underwent diffusion-weighted
      imaging and fluid-attenuated inversion recovery MR imaging performed, on average,
      3 days before and 12 hours after CEA. Diffusion-weighted images were acquired in
      three orthogonal directions at b = 900. Pre- and postoperative neurologic
      examinations were performed by the same physician. RESULTS: After endarterectomy,
      4.0% of the patients (one of 25 patients) showed a single, cortical focus of
      restricted diffusion and new fluid-attenuated inversion recovery hyperintensity,
      measuring <1 cm in diameter, ipsilateral to the CEA. The postoperative neurologic
      examination showed no change in status from the preoperative baseline state. This
      patient had an intraoperative course complicated by the development of a large
      luminal thrombus, necessitating thrombectomy. CONCLUSION: The use of diffusion
      weighted imaging may serve to improve conspicuity of clinically silent infarcts
      after CEA. An important next step is to determine the risk factors that
      predispose to detectable parenchymal ischemic events.

PMID- 11290473
TI  - Correlation of early CT signs in the deep middle cerebral artery territories with
      angiographically confirmed site of arterial occlusion.
AB  - BACKGROUND AND PURPOSE: Early CT signs in the deep middle cerebral artery (MCA)
      territories have been reported to be seen at the initial period of ischemia. We
      attempted to investigate the incidence of parenchymal hypodensity within 3 hours
      after ischemic onset among patients with angiographically proved embolic MCA
      occlusion and to assess the correlation of subtle hypodensity in the deep MCA
      territories with involvement of the lenticulostriate arteries in the presence of
      ischemia. METHODS: Fifty CT images obtained within 3 hours after onset of embolic
      MCA occlusion were retrospectively reviewed by three neurosurgeons who were aware
      of clinical features. Early CT signs in the deep MCA territories were divided
      into three grades according to their anatomic location: grade I, normal basal
      ganglia with hypodensity localized to the insula; grade II, partial obscuration
      of the posterolateral part of the putamen; and grade III, hypodensity of the
      entire lentiform nucleus. A grade I CT sign was considered to be a negative
      finding for lenticulostriate artery involvement, whereas grade II and III CT
      signs were considered to be positive findings. Site of occlusion and involvement
      of the lenticulostriate arteries were confirmed by angiography. RESULTS: Thirty
      eight (76%) of 50 patients had early CT signs in the deep MCA territories.
      Sensitivity and specificity of a grade I CT sign indicating absence of
      lenticulostriate artery involvement in ischemia were 65% and 87%, respectively.
      On the other hand, sensitivity and specificity of grade II and grade III CT signs
      for presence of lenticulostriate artery involvement in ischemia were 77% and
      100%, respectively. Grade II CT signs resulted from various sites of occlusion,
      whereas grade III was unequivocally predictive of proximal occlusion to all of
      the lenticulostriate arteries. CONCLUSION: Involvement of the lenticulostriate
      arteries may be presumed by precise evaluation of subtle, CT-revealed hypodensity
      in the deep MCA territories, even within 3 hours of ischemic onset.

PMID- 11290474
TI  - Astrocytic swelling in the ipsilateral substantia nigra after occlusion of the
      middle cerebral artery in rats.
AB  - BACKGROUND AND PURPOSE: Focal cerebral ischemia results in neuronal changes in
      remote areas that have fiber connections with the ischemic area. We reported
      previously that a high-signal-intensity lesion was observed in the substantia
      nigra after striatal infarction on T2-weighted MR images in both clinical and
      experimental cases. However, the origin of these changes in signal intensity
      remains unclear. The aim of this study was to investigate the nigral changes by
      examining the correlation between the apparent diffusion coefficient (ADC) and
      the tissue structure. METHODS: Sprague-Dawley rats were subjected to middle
      cerebral artery occlusion. Four days after the occlusion, when T2-weighted images
      revealed the presence of an area of high signal intensity in the ipsilateral
      substantia nigra, diffusion-weighted imaging was performed using a 4.7-T
      superconductive MR unit, and the ADCs were calculated and imaged. Histopathologic
      examination by both light and electron microscopy was performed on day 4 after
      surgery. RESULTS: Diffusion-weighted images showed an area of high signal
      intensity in the ipsilateral substantia nigra, and the ADC map revealed uniform
      reduction of the ADC in this area. Swelling of astrocytic end-feet was observed,
      especially in the pars reticulata. CONCLUSION: These findings suggest that MR
      changes in the ipsilateral substantia nigra after striatal injury consist mainly
      of swelling in the astrocytic end-feet.

PMID- 11290475
TI  - Enhancing patterns in multiple sclerosis: evolution and persistence.
AB  - BACKGROUND AND PURPOSE: Contrast enhancement on MR images of patients with
      multiple sclerosis (MS) is known to be associated with abnormalities of the blood
      brain barrier (BBB). However, little is known about diagnostic patterns and
      common features of enhanced MS lesions. This study was designed to evaluate
      initial enhancement patterns, changes in these enhancing patterns, and duration
      of enhancement in a cohort of patients with MS. METHODS: Twenty-five patients
      with clinically definite MS were studied retrospectively. The appearance of
      enhancing lesions and sequential changes in the appearance on axial contrast
      enhanced spin-echo images were evaluated. The enhancing lesions were classified
      as nodular, ringlike, or "other" (eg, arclike). RESULTS: Of 301 new enhancing
      lesions, 205 (68%) showed nodular enhancement, 70 (23%) a ring pattern, and 26
      (9%) a pattern neither nodular nor ringlike (eg, arclike). Two hundred eighty
      (93%) of 301 enhancing lesions disappeared within 6 months, and seven (2%)
      lesions showed persistent enhancement longer than 6 months. The other 14 (5%)
      lesions, which disappeared by the time of the next scan, were excluded, because
      the course between two examinations was longer than 6 months. Of nine persisting
      nodular enhancing lesions on the follow-up images, seven were decreased in size,
      whereas all of two persisting ringlike enhancing lesions on the follow-up images
      were larger than before. CONCLUSION: Nodular enhancement is the predominant
      enhancement pattern for new MS lesions, and the temporal course of enhancement is
      usually shorter than 6 months. The appreciation of the evolution of MS-enhanced
      lesions aids in both identifying new MS lesions and distinguishing these lesions
      from other pathologic entities. This may be helpful in clinically evaluating the
      stage of MS lesions.

PMID- 11290476
TI  - Variations of the basal vein: identification using three-dimensional CT
      angiography.
AB  - BACKGROUND AND PURPOSE: The basal vein of Rosenthal (BVR) presents with many
      variations because of its origin in the secondary longitudinal anastomoses
      between embryonic veins. The variations were evaluated by 3D CT angiography
      imaging. METHODS: Three-dimensional CT angiograms in the axial stereoscopic view
      and other directions constructed by the voxel transmission method and maximum
      intensity projection (MIP) images were obtained in 500 sides of 250 patients.
      RESULTS: The BVR flowed into the great vein of Galen in 87.8%, but the
      anastomoses between the first and second segments were not confirmed in 36.9% of
      this type. The first segments with hypoplastic or aplastic anastomoses flowed
      into the cavernous sinus or the sphenoparietal sinus. Therefore, typical BVRs
      with these anastomoses accounted only for 55.4% of all sides. More than one
      fourth of the typical type also entered the anterior veins such as the cavernous
      sinus. Drainage was to the lateral mesencephalic vein in 5.6%, peduncular vein in
      1.6%, and lateral or medial tentorial sinus in 5.0%. CONCLUSION: Variations of
      the BVR can be classified on the basis of the five drainage pathways formed
      during the early embryonic stage. Three-dimensional CT angiography can show the
      stereoscopic anatomy and the main drainage routes, but not hypoplastic veins,
      which are only visible on MIP images.

PMID- 11290477
TI  - Imaging findings in rabies encephalitis.
AB  - SUMMARY: Rabies encephalitis is perhaps one of the few infectious diseases that
      command attention and fear not only from the layman but also from physicians. The
      unique mode of transmission, the virtually exclusive neurotransmission shown by
      the agent, and the complete hopelessness of the established disease sets rabies
      apart from other zoonoses transmitted to man. Rabies encephalitis is a fatal
      disease and its diagnosis is usually based on the clinical presentations and
      findings. Hence, imaging in rabies is seldom done, and imaging findings in rabies
      encephalitis have rarely been described. We present the imaging findings in two
      confirmed cases of rabies encephalitis in which antemortem diagnosis was obtained
      by corneal impression smears showing the presence of viral antigens. The
      differential diagnosis of the imaging findings as well as the role and the
      relevance of imaging in the diagnosis of this disease are discussed. The current
      literature on the subject is also reviewed.

PMID- 11290478
TI  - Scan-rescan variation of measures derived from brain magnetization transfer ratio
      histograms obtained in healthy volunteers by use of a semi-interleaved
      magnetization transfer sequence.
AB  - SUMMARY: A novel semiinterleaved gradient-echo (GE) sequence for quantitative
      measurement of magnetization transfer ratio (MTR) is described. With this
      sequence, several lines of k-space are collected for the non-MT image then
      several lines are collected for the MT image, thus building up the entire k-space
      in distinct acquisition blocks, with a good trade-off between motion-induced
      misregistration and degree of MT effect. The scan-rescan coefficients of
      variation for several MTR histogram-derived measures from 10 healthy volunteers
      scanned serially with this semiinterleaved sequence proved to be lower than those
      achieved using a conventional GE sequence. This sequence may be useful in a
      clinical environment to measure MTR changes over time more reliably than when
      acquiring the non-MT and MT images sequentially, which inevitably are affected by
      patient motion.

PMID- 11290479
TI  - Outcome of stroke patients without angiographically revealed arterial occlusion
      within four hours of symptom onset.
AB  - BACKGROUND AND PURPOSE: Follow-up imaging data from stroke patients without
      angiographically apparent arterial occlusions at symptom onset are lacking. We
      reviewed our Emergency Management of Stroke (EMS) trial experience to determine
      the clinical and imaging outcomes of patients with ischemic stroke who showed no
      arterial occlusion on angiograms obtained within 4 hours of symptom onset.
      METHODS: All patients in this report were participants in the EMS trial that was
      designed to address the safety and potential efficacy of combined IV and
      intraarterial thrombolytic therapy with recombinant tissue plasminogen activator
      (rt-PA) in patients with acute ischemic stroke. RESULTS: Thirty-five patients
      were randomized to receive either IV rt-PA (n = 17) or placebo (n = 18), followed
      by cerebral angiography. No symptomatic arterial occlusion was evident in 10
      (29%) of the 34 patients. Eight (80%) of 10 patients without angiographically
      apparent clot within 4 hours of symptom onset had a new cerebral infarction
      confirmed on follow-up brain imaging. The median 72-hour infarction volume was
      2.4 cc (range, 1-30 cc). Four of the 10 "no-clot" patients had a favorable 3
      month outcome as assessed by Barthel Index (score, 95 or 100) and modified Rankin
      Scale (score, 0 or 1). The six remaining patients had 3-month Rankin Scale scores
      of 1 (Barthel of 90), 2, 3, 4, or 5. CONCLUSION: Acute ischemic stroke patients
      with a neurologic deficit but a negative angiogram during the first 4 hours after
      symptom onset usually develop image-documented cerebral infarction, and
      approximately half suffer from long-term functional disability. The two most
      likely explanations for negative angiograms are very early irreversible ischemic
      damage despite recanalization or ongoing ischemia secondary to clot in non
      visible penetrating arterioles or in the microvasculature.

PMID- 11290480
TI  - Europium fluorescence to visualize N-butyl 2-cyanoacrylate in embolized vessels
      of an arteriovenous malformation swine model.
AB  - BACKGROUND AND PURPOSE: Standard tissue staining using the lipid dye Oil-Red-O
      has been previously applied to stain vessel specimens, which were embolized with
      a mixture of n-butyl 2-cyanoacrylate (NBCA) and oil (Lipiodol). That technique,
      however, results in nonspecific and nonquantitative staining that does not
      provide the necessary differentiation between NBCA and Lipiodol. We present an
      innovative staining procedure that quantifies NBCA within treated tissues.
      METHODS: An arteriovenous malformation (AVM) model in swine was used to evaluate
      the polymerization characteristics of various ratios of Lipiodol/NBCA/glacial
      acetic acid (GAA) mixtures. To determine the depth of NBCA penetration within the
      AVM model and to characterize the polymerization patterns of various mixtures
      within the vessel, histologic cross- and longitudinal sections were prepared for
      microscopy. These paraffin-embedded tissue sections were stained with a europium
      aryl-beta-diketone complex (TEC) to improve differentiation between NBCA and
      Lipiodol. Quantification of NBCA and Lipiodol within the lumen of rete cross
      sections was accomplished using image analysis software to determine percent
      luminal area occluded by embolization. RESULTS: Upon application of TEC, intense
      europium fluorescence was seen when the tissue samples were excited by low-power
      UV light (excitation at 365 nm; emission at 614 nm). The area of europium
      intensity within the lumen corresponded to NBCA concentration, and addition of
      GAA aided the NBCA distribution throughout the lumen without affecting
      fluorescence intensity. It was seen that NBCA could be easily differentiated from
      Lipiodol and that quantification could be readily performed on these sections
      because of the improved differentiation. For the case of a 50:50 (vol. %) mixture
      with an added 20 microL of GAA, luminal area distribution of Lipiodol, NBCA, and
      blood products was 42.6 +/- 3.5%, 33.8 +/- 5.7%, and 23.7 +/-2.7%, respectively.
      CONCLUSION: The rare earth metal europium, when added as a fluorescent chelate
      compound to histologic tissue sections, allowed for differentiation between NBCA
      and Lipiodol with good detail. These results have facilitated further
      characterization of NBCA polymerization for the use of AVM embolization.

PMID- 11290481
TI  - Serial angiography in an elastase-induced aneurysm model in rabbits: evidence for
      progressive aneurysm enlargement after creation.
AB  - BACKGROUND AND PURPOSE: Among the several reports of elastase-induced aneurysm
      models, only the rabbit common carotid artery (CCA) model has been used for
      testing endovascular occlusion devices. Our purpose was to study the growth
      characteristics of an elastase-induced aneurysm model in rabbits for the purpose
      of determining whether delayed aneurysm enlargement occurs after creation.
      METHODS: Nine New Zealand White rabbits (3-4 kg) were used in this study. All
      study animals underwent surgery to isolate the right CCA. In three control
      animals, the lumen was incubated with saline and iodinated contrast material for
      20 minutes. In six test animals, the lumen of the CCA was incubated with porcine
      elastase for 20 minutes. In all study animals, the distal right CCA was ligated.
      IV digital subtraction angiography was performed on postprocedural days 3, 5, 7,
      14, 28, 35, 56, 84, and 112. Using an external sizing reference, the width and
      height of patent arterial segments at the right CCA origin were measured by two
      observers. For test animals, aneurysm dimensions were compared between early and
      late time points by using the Student's t test. RESULTS: In the control (no
      elastase) animals, slitlike cavities at the origin of the right CCA decreased in
      size over time to become nearly obliterated by 21 days. Conversely, a short
      segment of the proximal CCA remained widely patent in all six test animals. With
      the exception of a single time point in one test animal, all "aneurysm" cavities
      in the test animals were dilated as compared with the normal diameter of the CCA.
      On day 3 after surgery, the mean width and height of the aneurysm cavities in the
      test animals were 3.2 +/- 0.6 and 6.0 +/- 1.3 mm, respectively. Compared with
      dimensions at day 3, aneurysms in test animals were larger at day 14, with mean
      width and height of 4.1 +/- 1.7 and 8.3 +/- 1.9 mm, respectively (P =.02).
      Aneurysms in test animals had increased further at 21 days compared with 14 days
      (P =.01). Compared with measurements obtained at 21 days, dimensions remained
      essentially unchanged at 28 and 35 days. Thirty-five days after surgery, mean
      width and height were 5.0 +/- 0.9 and 10.0 +/- 2.2 mm, respectively. Follow-up
      imaging performed < or = 4 months after aneurysm creation showed no further
      change in aneurysm dimensions. CONCLUSION: Elastase incubation and vessel
      ligation results in patent aneurysmally dilated arterial segments at the origin
      of the right CCA in rabbits. These aneurysms show progressive increases in
      diameter over time, finally stabilizing at approximately 1 month. Our data, which
      show early progressive aneurysm enlargement, suggest that this model may be used
      for the study of systemic therapies aimed at diminishing aneurysm rest regrowth
      and also indicate that embolization of these model aneurysms should be delayed at
      least 21 days after aneurysm creation.

PMID- 11290482
TI  - Transradial approach for diagnostic selective cerebral angiography: results of a
      consecutive series of 166 cases.
AB  - BACKGROUND AND PURPOSE: Diagnostic selective cerebral angiography is commonly
      performed via transfemoral and transbrachial approaches. With these approaches,
      however, patients occasionally suffer serious complications. The purpose of this
      study was to evaluate the feasibility, efficacy, and safety of a transradial
      approach as an alternative to the transfemoral and transbrachial approaches.
      METHODS: Between October 1998 and September 1999, transradial cerebral
      angiography was performed in 166 consecutive patients in a single center as a
      diagnostic procedure. Before the procedure, we confirmed the collateral blood
      supply to the hand from the ulnar artery using a modified Allen test. Regular
      catheterization techniques were practiced using our newly designed 120-cm-long 4F
      catheter. In 42 patients, anticoagulant and/or antiplatelet therapy was given
      perioperatively. RESULTS: Twelve of the 166 patients proved to be poor candidates
      for the transradial approach, owing to restlessness (n = 9), lack of collateral
      blood supply via the ulnar artery (n = 2), and brachial artery stenosis (n = 1).
      The radial artery was successfully punctured and cannulated in the remaining 154
      patients. Selective catheterization of the intended vessels was obtained in all
      carotid and vertebral angiographic procedures with no major vascular
      complications. CONCLUSION: Compared with transfemoral and transbrachial
      approaches, the transradial approach is a less invasive and safer technique for
      selective cerebral angiography and may warrant consideration as a standard
      procedure. Anticoagulant or antiplatelet therapy need not be discontinued for
      this method.

PMID- 11290483
TI  - Injection of air bubbles during flushing of angiocatheters: an in vitro trial of
      conventional hardware and techniques.
AB  - BACKGROUND AND PURPOSE: Injected air bubbles are a well-accepted cause of stroke
      during cerebral angiography. We used an in vitro model to determine the frequency
      of occurrence of air emboli during catheter flushing using conventional hardware
      and techniques. METHODS: Two experimental models were used in this study. The
      first incorporated an in-line bubble trap. Ten members of our angiography section
      flushed this system in their usual fashion and then with two modifications of the
      hardware. The trap was inspected after each trial of seven injections and any
      visible bubble was measured with calipers. The second model used a peristaltic
      pump along with a transcranial Doppler device to look at the relative number of
      bubble events with modifications of the flush solution or technique. RESULTS: The
      closed-flush set in common usage in our department caused an increase in the
      number of visible bubbles in the trap as compared with an open basin. Degassing
      the solution and delaying injection decreased the number of bubble events noted
      in model 2. CONCLUSION: Bubble emboli are commonplace during flushing of
      angiography catheters when using conventional techniques and equipment.

PMID- 11290484
TI  - Endovascular treatment of hemorrhage after tonsillectomy in children.
AB  - SUMMARY: Endovascular therapy for hemorrhage after tonsillectomy or adenoidectomy
      is an important adjunct to the definitive treatment of this life-threatening
      occurrence. We report two cases of hemorrhage after tonsillectomy and/or
      adenoidectomy and describe the endovascular management of this complication in
      children.

PMID- 11290485
TI  - Distal superior cerebellar artery aneurysm presenting with cerebellar infarction:
      report of two cases.
AB  - SUMMARY: We report two cases of aneurysm of the distal branches of the superior
      cerebellar artery presenting with cerebellar infarction. In both cases, the
      diagnosis required close correlation of the findings from different imaging
      techniques, as catheter angiography failed to opacify the lesions. In one patient
      endovascular parent vessel occlusion was performed, whereas in the second patient
      the aneurysm thrombosed spontaneously. We describe the clinical and radiologic
      presentation of these aneurysms and discuss their pathogenesis, diagnosis, and
      treatment.

PMID- 11290486
TI  - Analysis of slipstream flow in a wide-necked basilar artery aneurysm: evaluation
      of potential treatment regimens.
AB  - SUMMARY: A replica of a lethal wide-necked basilar artery aneurysm was created by
      casting a deceased patient's brain vessels and then placing the replica in a
      circuit of pulsating optically clear non-Newtonian fluid. Individual fluid
      slipstreams were opacified with isobaric dyes, and images were recorded on film.
      Studies were completed on the vascular replica, then were repeated, first after
      placement of a stent across the aneurysm neck and then after placement of
      Guglielmi detachable coils into the aneurysm sac through the stent. The
      slipstreams entered the untreated aneurysm via the distal aneurysm neck (the
      inflow zone), impacting against the distal lateral aneurysm wall. When the stent
      was placed across the aneurysm neck, the slipstreams lost coherence and did not
      strike the aneurysm sidewall. Placing the coils further disturbed and reduced
      aneurysmal flow, especially when the coils filled the inflow zone at the distal
      lateral aneurysm sac.

PMID- 11290487
TI  - Endovascular access to the meningohypophyseal trunk.
AB  - SUMMARY: We describe a novel technique to selectively catheterize the
      meningohypophyseal trunk (MHT) and its branches. We emphasize the difficulty in
      accessing the MHT via an ipsilateral approach because of the geometric
      orientation of this vessel to the parent internal carotid artery.

PMID- 11290488
TI  - The accuracy of sonography for evaluation of internal derangement of the
      temporomandibular joint in asymptomatic elementary school children: comparison
      with MR and CT.
AB  - BACKGROUND AND PURPOSE: In order to clarify the incidence and evolution of disk
      displacement in the temporomandibular joint (TMJ) in children, we performed a
      longitudinal analysis in 18 subjects. Some investigators have suggested that
      sonography can provide information about the articular disk position of the TMJ.
      The purpose of this study was to determine the diagnostic accuracy of sonography
      for revealing internal derangement of the TMJ in elementary school children
      compared with our standard of reference, MR imaging and helical CT. METHODS:
      Eighteen children were examined using both sonography and MR imaging or helical
      CT or both. The sonographically revealed distance between the articular capsule
      and the lateral surface of the mandibular condyle was measured and compared with
      that obtained by MR or helical CT scanning. RESULTS: Compared with our MR/CT
      standard of reference, sonography revealed a sensitivity of 83%, a specificity of
      96%, and an accuracy of 92% for identifying disk displacement (defined as a
      distance of 4 mm or more between the articular capsule and the lateral surface of
      the mandibular condyle). CONCLUSION: Although sonography's sensitivity,
      specificity, and accuracy for the diagnosis of disk displacement were slightly
      inferior to those of MR or helical CT, we assert it is a useful imaging method
      for longitudinal investigations of a large group of elementary school children.
      Internal derangement of the TMJ should be suspected if sonography reveals a
      distance between the articular capsule and the lateral surface of the mandibular
      condyle of 4 mm or more.

PMID- 11290489
TI  - Power Doppler sonography to differentiate tuberculous cervical lymphadenopathy
      from nasopharyngeal carcinoma.
AB  - BACKGROUND AND PURPOSE: Tuberculous lymphadenitis and metastatic nodes from
      nasopharyngeal carcinoma are common in Asians and are often indistinguishable
      clinically. Because their treatment depends on prompt diagnosis, we undertook
      this study to evaluate if power Doppler sonography could distinguish these two
      pathologic abnormalities. The intranodal vascular appearances of tuberculous neck
      nodes are compared with benign reactive neck nodes and metastatic nodes from
      nasopharyngeal carcinoma. METHODS: The appearances of power Doppler sonograms of
      42 tuberculous nodes were compared with 28 metastatic nodes from nasopharyngeal
      carcinoma and 27 benign reactive nodes. The intranodal distribution of vessels
      and the intranodal vascular resistance of vessels were compared among these three
      groups. All examinations were performed by the same sonologist (A.A.), who had
      more than 3 years' scanning experience, and all data analysis was performed by
      the same investigator (M.Y.). RESULTS: The intranodal vascular distribution in
      tuberculous nodes was varied and simulated both benign and malignant disease.
      Avascularity of nodes and displacement of hilar vascularity were frequent in
      tuberculous nodes. Metastatic nodes from nasopharyngeal carcinoma (resistive
      index [RI], 0.81+/-0.09; pulsatile index [PI], 1.91+/-0.81) had a higher vascular
      resistance than did tuberculous nodes (RI, 0.71+/-0.11; PI, 1.34+/-0.55).
      Tuberculous nodes had a higher vascular resistance than did reactive nodes (RI,
      0.66+/-0.09; PI, 1.10+/-0.26). CONCLUSION: Avascularity, displaced hilar vessels,
      and low intranodal vascular resistance are clues that may suggest the tuberculous
      nature of neck nodes. However, there is overlap of appearance between tuberculous
      nodes, benign reactive neck nodes, and metastatic nodes. Thus, histologic
      analysis is often required for a definitive diagnosis.

PMID- 11290490
TI  - "Puffed-cheek" CT improves evaluation of the oral cavity.
AB  - BACKGROUND AND PURPOSE: Maneuvers that distend a lumen facilitate radiographic
      examinations. In evaluation of the upper aerodigestive tract, Valsalva and
      phonation maneuvers complement barium fluoroscopy. The current work investigates
      "puffed-cheek" CT to improve visualization of oral cavity tumors. METHODS: Seven
      patients (ages 17 to 86 years) underwent conventional and puffed-cheek CT. Five
      had squamous cell carcinoma, one had benign verrucous hyperplasia of the buccal
      mucosa, one had "cheek swelling," and one had a pulsatile cheek mass.
      Conventional contrast-enhanced axial CT scans (3-mm thick, no interslice gap)
      were obtained through the oral cavity and neck. Each patient then pursed the lips
      and puffed out the cheeks, and axial images were obtained through the oral cavity
      (puffed-cheek scans). RESULTS: Three patients had normal conventional CT scans
      whereas puffed-cheek scans clearly showed the mass. Conventional CT in three
      patients showed a mass inseparable from two mucosal surfaces whereas puffed-cheek
      images clearly showed which surface the tumor involved. Two patients had normal
      conventional and puffed-cheek CT studies; in one, the physical examination was
      also normal. The other patient was a teenager with orthodontic appliances that
      created artifacts on both conventional and puffed-cheek images. Conventional
      angiography in this patient revealed a facial artery aneurysm. CONCLUSION: The
      puffed-cheek CT maneuver is easily taught, and patients comply readily. Puffed
      cheek CT scans provide a clearer and more detailed evaluation of mucosal surfaces
      of the oral cavity than do conventional scans. In selected patients, the puffed
      cheek technique can supplement conventional CT studies.

PMID- 11290491
TI  - Transnasal access for sampling a skull base lesion.
AB  - SUMMARY: Transnasal needle access for sampling was used in two patients with
      posterior nasopharyngeal lesions. The procedure was performed under CT guidance.
      This new technique is simple and appears suitable for selected cases. The two
      cases and the details of the procedure are described.

PMID- 11290493
TI  - The cerebral angiographic findings in Cogan syndrome.
AB  - SUMMARY: Cogan syndrome is an uncommon disorder of unknown etiology characterized
      by vestibuloauditory dysfunction and nonsyphilitic interstitial keratitis. To our
      knowledge, the case herein is the first report to demonstrate the cerebral
      angiographic findings of a patient with this syndrome.

PMID- 11290492
TI  - Malignant peripheral nerve sheath tumor in the parapharyngeal space: tumor spread
      through the eustachian tube.
AB  - SUMMARY: We report the CT and MR findings in a patient with malignant peripheral
      nerve sheath tumor in the parapharyngeal space who had neither a family history
      nor stigmata of neurofibromatosis. A high-resolution CT scan of the temporal bone
      revealed bony erosion and widening of both the foramen ovale and the bony portion
      of the eustachian tube. A temporal bone MR image showed an intensely enhancing
      solid mass in the parapharyngeal space, which extended into the middle ear cavity
      via the eustachian tube.

PMID- 11290494
TI  - Hemangioendothelioma of the temporal bone with radiologic findings resembling
      hemangioma.
AB  - SUMMARY: Hemangioendotheliomas are rare vascular tumors that can affect bone.
      They account for 0.5% to 1.0% of malignant primary bone tumors. Only four cases
      have been reported involving the temporal bone. A 5-year-old child with grade II
      hemangioendothelioma of the right temporal bone is presented, and the radiologic
      findings on different imaging studies are described. The patient was treated with
      preoperative endovascular embolization followed by wide surgical resection. The
      imaging patterns of this malignant tumor may be similar to those of a benign
      lesion.

PMID- 11290495
TI  - Left vocal cord paralysis associated with long-standing patent ductus arteriosus.
AB  - SUMMARY: Left vocal cord paralysis in association with patent ductus arteriosus
      is unusual. We report a patient with long-standing patent ductus arteriosus (PDA)
      in whom CT studies obtained before and after paralysis developed showed an
      interval increase in size of the pulmonary trunk. The pathogenesis of left vocal
      cord paralysis in association with long-standing PDA is discussed.

PMID- 11290496
TI  - Global estimation of myelination in the developing brain on the basis of
      magnetization transfer imaging: a preliminary study.
AB  - BACKGROUND AND PURPOSE: In the developing brain, myelination occurs in an orderly
      and predetermined sequence. The aim of this study was to determine whether such
      changes can be tracked using volumetric magnetization transfer imaging. METHODS:
      Three-dimensional magnetization transfer imaging was performed in 50 children
      (age range, 0.6-190 months) with no evidence of developmental delay or structural
      abnormalities. Volumetric magnetization transfer ratio (MTR) parameters generated
      of the whole brain were mean MTR and height and location of the MTR histogram
      peak. Relationships between volumetric MTR parameters and age were assessed using
      nonlinear regression analysis. RESULTS: With age, all volumetric MTR parameters
      changed exponentially in a way that was best expressed by the function y = a +
      b.exp(-x/c) (P < .0001). The peak height of the MTR histogram was the parameter
      that changed most predictably and that continued to change for the longest period
      of time. CONCLUSION: With this preliminary study, we show that by using
      volumetric MTR analysis, it is possible to monitor changes in the developing
      brain, presumably the myelination progress. This method has a potential role for
      detecting myelination disorders in the pediatric population, for studying the
      natural history of these diseases, and for monitoring the effects of treatment.

PMID- 11290497
TI  - Prenatal diagnosis and postnatal follow-up of pericallosal lipoma: report of
      seven new cases.
AB  - BACKGROUND AND PURPOSE: Pericallosal lipomas are rare tumors. Few reports have
      included their imaging characteristics. Furthermore, little is known about their
      evolutive course. Our purpose was to describe the imaging features of seven cases
      of pericallosal lipoma diagnosed in utero and followed up after birth. METHODS:
      We reviewed seven cases of pericallosal lipoma diagnosed by obstetric sonography
      (n = 7) and examined by fetal MR imaging (n = 5). Analysis of the complementary
      findings provided by fetal MR imaging was conducted. All findings were correlated
      with the postnatal imaging and clinical findings. RESULTS: Obstetric sonography
      easily showed the pericallosal lipoma in all seven patients. In one, however, it
      was misinterpreted as intracranial hemorrhage. The morphology and integrity of
      the underlying corpus callosum were less easy to assess by using sonography.
      Fetal MR imaging confirmed the fatty content and location of the lesion in all
      five cases. It showed the choroidal extension in two patients and the type of
      associated callosal anomaly in another patient better than did sonography. In two
      patients, the lipoma grew, as revealed by subsequent postnatal MR imaging. The
      results of the neurologic examinations remained normal for the five surviving
      patients at a mean follow-up of 3 years (1 month-9 years). CONCLUSION: Obstetric
      sonography is able to easily show pericallosal lipoma. Fetal MR imaging may be
      useful to characterize the lipomatous nature and the extension of the lipoma and
      the status of the corpus callosum. Long-term follow-up is necessary to understand
      the clinical consequences of such lesions.

PMID- 11290498
TI  - T2 relaxation measurements in X-linked adrenoleukodystrophy performed using dual
      echo fast fluid-attenuated inversion recovery MR imaging.
AB  - SUMMARY: The purpose of this study was to determine whether dual-echo fast fluid
      attenuated inversion recovery MR imaging and corresponding T2 brain maps can show
      different zones in the affected white matter of patients with cerebral X-linked
      adrenoleukodystrophy. Ten male patients with cerebral X-linked
      adrenoleukodystrophy underwent imaging performed using dual-echo fast fluid
      attenuated inversion recovery and dual-echo conventional spin-echo MR sequences.
      Corresponding T2 relaxation maps of the brain were generated. On the basis of
      dual-echo fast fluid-attenuated inversion recovery images and T2 maps, the
      affected white matter could be divided into two distinct zones in four patients
      with cerebral X-linked adrenoleukodystrophy.

PMID- 11290499
TI  - MR brain imaging of fucosidosis type I.
AB  - SUMMARY: Fucosidosis is a rare autosomal recessive lysosomal storage disease with
      the main clinical findings of progressive neuromotor deterioration, seizures,
      coarse facial features, dysostosis multiplex, angiokeratoma corporis diffusum,
      visceromegaly, recurrent respiratory infections, and growth retardation.
      Fucosidosis type I rapidly evolves toward a progressive neurologic deterioration
      and death. We report MR imaging findings of the brain of three patients with
      fucosidosis type I, including previously unreported findings, to expand the
      knowledge of the neuroradiologic spectrum of the disease.

PMID- 11290500
TI  - CT-guided biopsy of focal lesions in patients with multiple myeloma may reveal
      new and more aggressive cytogenetic abnormalities.
AB  - BACKGROUND AND PURPOSE: Cytogenetic abnormalities, especially chromosome 13
      deletion, are high-risk factors for multiple myeloma. Attaining the highest
      detection rates of cytogenetic abnormalities is important to provide accurate
      prognostic information to the referring oncologist. The purpose of this study was
      to use CT-guided percutaneous fine-needle aspiration bone biopsy (CT-guided FNA)
      of MR-detected focal lesions in patients with multiple myeloma to increase
      identification of abnormal cytogenetics. METHODS: Patients enrolled in two
      clinical trials for myeloma therapy underwent MR imaging of the entire spine and
      pelvis. CT-guided FNA biopsy samples obtained from MR-detected focal lesions in
      these patients were sent for cytogenetic analysis. FNA results were then compared
      with random bone marrow sampling of the iliac crest done at or near the same time
      as the FNA to provide the data revealed in this study. RESULTS: Forty-one
      patients (47 lesions) in one of the trials and 37 patients (38 lesions) in the
      other trial had biopsies performed. CT-guided FNA revealed cytogenetic
      abnormalities in 21% of the total patient population and new information in
      nearly 10% of the patients in one trial and in 20% of those in the other trial.
      CONCLUSION: CT-guided biopsy of MR-detected focal lesions is a safe technique
      that can provide important cytogenetic information in a significant number of
      patients with multiple myeloma not identified during random marrow sampling.

PMID- 11290501
TI  - The value of MR neurography for evaluating extraspinal neuropathic leg pain: a
      pictorial essay.
AB  - SUMMARY: Fifteen patients with neuropathic leg pain referable to the lumbosacral
      plexus or sciatic nerve underwent high-resolution MR neurography. Thirteen of the
      patients also underwent routine MR imaging of the lumbar segments of the spinal
      cord before undergoing MR neurography. Using phased-array surface coils, we
      performed MR neurography with T1-weighted spin-echo and fat-saturated T2-weighted
      fast spin-echo or fast spin-echo inversion recovery sequences, which included
      coronal, oblique sagittal, and/or axial views. The lumbosacral plexus and/or
      sciatic nerve were identified using anatomic location, fascicular morphology, and
      signal intensity as discriminatory criteria. None of the routine MR imaging
      studies of the lumbar segments of the spinal cord established the cause of the
      reported symptoms. Conversely, MR neurography showed a causal abnormality
      accounting for the clinical findings in all 15 cases. Detected anatomic
      abnormalities included fibrous entrapment, muscular entrapment, vascular
      compression, posttraumatic injury, ischemic neuropathy, neoplastic infiltration,
      granulomatous infiltration, neural sheath tumor, postradiation scar tissue, and
      hypertrophic neuropathy.

PMID- 11290502
TI  - Spinal epidural extraskeletal Ewing sarcoma: MR findings in two cases.
AB  - SUMMARY: We report the CT myelography and MR findings of two cases of
      extraskeletal Ewing sarcoma involving the spinal epidural and paravertebral
      spaces in a middle-aged man (case 1) and a young woman (case 2). In both cases CT
      myelography showed epidural and paravertebral masses on one side, with widening
      of the ipsilateral neural foramina at the C5-C6 level in case 1 and at the C7-T1
      level in case 2. On MR images, the masses were isointense to muscle on T1
      weighted images, hyperintense on T2-weighted images, and showed moderate
      enhancement on contrast-enhanced T1-weighted images. In one case, all pulse
      sequences showed linear signal voids, representing the vertebral artery
      encasement within the mass. The intradural component connected with the main mass
      was detected in the other case.

PMID- 11290503
TI  - Spinal intradural extramedullary capillary hemangioma: MR imaging findings.
AB  - SUMMARY: Spinal intradural extramedullary capillary hemangiomas are extremely
      rare. We present the MR imaging and histologic findings in three patients with
      this abnormality. The three patients were men who had symptoms of either
      myelopathy (n = 2) or radiculopathy (n = 1). The tumors were well demarcated, 1.5
      2.0 cm in diameter, and were located at the posterior or posterolateral portion
      of the thecal sac (one at the L1 level and the other two at the midthoracic
      level). On MR images, the tumor showed isointensity relative to the spinal cord
      on T1-weighted images, hyperintensity on T2-weighted images, and strong
      homogeneous enhancement on contrast-enhanced T1-weighted images in all three
      patients. In two patients, the dural tail sign was observed. Capillary hemangioma
      should be included in the differential diagnosis of a spinal intradural
      extramedullary tumor.

PMID- 11290504
TI  - Transcription factors in mouse lung development and function.
AB  - Development of the mouse lung initiates on day 9.5 postcoitum from the
      laryngotracheal groove and involves mesenchymal-epithelial interactions, in
      particular, those between the splanchnic mesoderm and epithelial cells (derived
      from foregut endoderm) that induce cellular proliferation, migration, and
      differentiation, resulting in branching morphogenesis. This developmental process
      mediates formation of the pulmonary bronchiole tree and integrates a terminal
      alveolar region with an extensive endothelial capillary bed, which facilitates
      efficient gas exchange with the circulatory system. The major function of the
      mesenchymal-epithelial signaling is to potentiate the activity or expression of
      cell type-specific transcription factors in the developing lung, which, in turn,
      cooperatively bind to distinct promoter regions and activate target gene
      expression. In this review, we focus on the role of transcription factors in lung
      morphogenesis and the maintenance of differentiated gene expression. These lung
      transcription factors include forkhead box A2 [also known as hepatocyte nuclear
      factor (HNF)-3beta], HNF-3/forkhead homolog (HFH)-8 [also known as FoxF1 or
      forkhead-related activator-1], HNF-3/forkhead homolog-4 (also known as FoxJ1),
      thyroid transcription factor-1 (Nkx2.1), and homeodomain box A5 transcription
      factors, the zinc finger Gli (mouse homologs of the Drosophila cubitus
      interruptus) and GATA transcription factors, and the basic helix-loop-helix Pod1
      transcription factor. We summarize the phenotypes of transgenic and knockout
      mouse models, which define important functions of these transcription factors in
      cellular differentiation and lung branching morphogenesis.

PMID- 11290505
TI  - Fishing for inflammatory cytokine-inducible genes with an old trick.

PMID- 11290506
TI  - Identification of genes induced by inflammatory cytokines in airway epithelium.
AB  - Epithelial cells lining the airways are thought to play a prominent role in
      respiratory diseases. We utilized cDNA representational difference analysis to
      identify the genes in which expression is induced by the proinflammatory
      cytokines tumor necrosis factor-alpha and interleukin-1beta in primary human
      bronchial epithelial cells and hence are relevant to airway inflammation.
      Hybridization of the subtraction product to arrayed cDNAs indicated that known
      tumor necrosis factor-alpha- and interleukin-1beta-inducible genes such as B94,
      Zfp36, and regulated on activation normal T cell expressed and secreted were
      represented, confirming the success of the subtraction experiment. A 1,152-clone
      library potentially representing genes with higher transcript levels in cytokine
      treated human bronchial epithelial cells was generated and sequenced. Sequence
      similarity searches indicated that these clones represented 57 genes of known
      function, 1 gene of unknown function, 6 expressed sequence tags, and 2 novel
      sequences. The expression of 19 of these clones was studied by a combination of
      Northern blotting and RT-PCR analyses and confirmation of differential expression
      for 10 known genes, 2 expressed sequence tags, and a novel sequence not
      represented in any of the public databases was obtained. Thus cDNA
      representational difference analysis was utilized to isolate known and novel
      differentially expressed genes, which putatively play a role in airway
      inflammation.

PMID- 11290507
TI  - Focus on "Hypoxic constriction of porcine distal pulmonary arteries: endothelium
      and endothelin dependence".

PMID- 11290508
TI  - Hypoxic constriction of porcine distal pulmonary arteries: endothelium and
      endothelin dependence.
AB  - To determine the role of endothelium in hypoxic pulmonary vasoconstriction (HPV),
      we measured vasomotor responses to hypoxia in isolated seventh-generation porcine
      pulmonary arteries < 300 microm in diameter with (E+) and without endothelium. In
      E+ pulmonary arteries, hypoxia decreased the vascular intraluminal diameter
      measured at a constant transmural pressure. These constrictions were complete in
      30-40 min; maximum at PO(2) of 2 mm Hg; half-maximal at PO(2) of 40 mm Hg;
      blocked by exposure to Ca(2+)-free conditions, nifedipine, or ryanodine; and
      absent in E+ bronchial arteries of similar size. Hypoxic constrictions were
      unaltered by indomethacin, enhanced by indomethacin plus N(G)-nitro-L-arginine
      methyl ester, abolished by BQ-123 or endothelial denudation, and restored in
      endothelium-denuded pulmonary arteries pretreated with 10(-10) M endothelin-1 (ET
      1). Given previous demonstrations that hypoxia caused contractions in isolated
      pulmonary arterial myocytes and that ET-1 receptor antagonists inhibited HPV in
      intact animals, our results suggest that full in vivo expression of HPV requires
      basal release of ET-1 from the endothelium to facilitate mechanisms of hypoxic
      reactivity in pulmonary arterial smooth muscle.

PMID- 11290509
TI  - Is there a role for store-operated calcium entry in vasoconstriction?

PMID- 11290510
TI  - Capacitative Ca(2+) entry in agonist-induced pulmonary vasoconstriction.
AB  - Agonist-induced increases in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in
      pulmonary artery (PA) smooth muscle cells (SMCs) consist of a transient Ca(2+)
      release from intracellular stores followed by a sustained Ca(2+) influx.
      Depletion of intracellular Ca(2+) stores triggers capacitative Ca(2+) entry
      (CCE), which contributes to the sustained increase in [Ca(2+)](cyt) and the
      refilling of Ca(2+) into the stores. In isolated PAs superfused with Ca(2+)-free
      solution, phenylephrine induced a transient contraction, apparently by a rise in
      [Ca(2+)](cyt) due to Ca(2+) release from the intracellular stores. The transient
      contraction lasted for 3-4 min until the Ca(2+) store was depleted. Restoration
      of extracellular Ca(2+) in the presence of phentolamine produced a contraction
      potentially due to a rise in [Ca(2+)](cyt) via CCE. The store-operated Ca(2+)
      channel blocker Ni(2+) reduced the store depletion-activated Ca(2+) currents,
      decreased CCE, and inhibited the CCE-mediated contraction. In single PASMCs, we
      identified, using RT-PCR, five transient receptor potential gene transcripts.
      These results suggest that CCE, potentially through transient receptor potential
      encoded Ca(2+) channels, plays an important role in agonist-mediated PA
      contraction.

PMID- 11290511
TI  - Pulmonary interstitial pressure and tissue matrix structure in acute hypoxia.
AB  - Pulmonary interstitial pressure was measured via micropuncture in anesthetized
      rabbits in normoxia and after breathing 12% O(2). In normoxia [arterial PO(2) =
      88 +/- 2 (SD) mmHg], pulmonary arterial pressure and pulmonary interstitial
      pressure were 16 +/- 8 and -9.6 +/- 2 cmH(2)O, respectively. After 6 h of hypoxia
      (arterial PO(2) = 39 +/- 16 mm Hg), the corresponding values were 30+/-8 and
      3.5+/-2.5 cm H(2)O (P<0.05). Pulmonary interstitial proteoglycan extractability,
      evaluated by hexuronate assay after 0.4 M guanidinium hydrochloride extraction,
      was 12.3, 32.4, and 60.6 microg/g wet tissue in normoxia and after 3 and 6 h of
      hypoxia, respectively, indicating a weakening of the noncovalent bonds linking
      proteoglycans to other extracellular matrix components. Gel filtration
      chromatography showed an increased fragmentation of chondroitin sulfate- and
      heparan sulfate-proteoglycans during hypoxic exposure, accounting for a loss of
      extracellular matrix native architecture and basement membrane structure. Gelatin
      zymography demonstrated increased amounts of the proteolytically activated form
      of gelatinase B (matrix metalloproteinase-9) after hypoxic exposure, providing
      evidence that the activation of proteinases may play a role in hypoxia-induced
      lung injury.

PMID- 11290512
TI  - Effect of protein kinase C inhibition on hypoxic pulmonary vasoconstriction.
AB  - The current study was done to test the hypothesis that protein kinase C (PKC)
      inhibitors prevent the increase in pulmonary vascular resistance and compliance
      that occurs in isolated, blood-perfused dog lungs during hypoxia. Pulmonary
      vascular resistances and compliances were measured with vascular occlusion
      techniques. Hypoxia significantly increased pulmonary arterial resistance,
      pulmonary venous resistance, and pulmonary capillary pressure and decreased total
      vascular compliance by decreasing both microvascular and large-vessel
      compliances. The nonspecific PKC inhibitor staurosporine (10(-7) M), the specific
      PKC blocker calphostin C (10(-7) M), and the specific PKC isozyme blocker Go-6976
      (10(-7) M) inhibited the effect of hypoxia on pulmonary vascular resistance and
      compliance. In addition, the PKC activator thymeleatoxin (THX; 10(-7) M)
      increased pulmonary vascular resistance and compliance in a manner similar to
      that in hypoxia, and the L-type voltage-dependent Ca(2+) channel blocker
      nifedipine (10(-6) M) inhibited the response to both THX and hypoxia. These
      results suggest that PKC inhibition blocks the hypoxic pressor response and that
      the pharmacological activation of PKC by THX mimics the hypoxic pulmonary
      vasoconstrictor response. In addition, L-type voltage-dependent Ca(2+) channel
      blockade may prevent the onset of the hypoxia- and PKC-induced vasoconstrictor
      response in the canine pulmonary vasculature.

PMID- 11290513
TI  - Alveolar epithelial barrier functions in ventilated perfused rabbit lungs.
AB  - We employed ultrasonic nebulization for homogeneous alveolar tracer deposition
      into ventilated perfused rabbit lungs. (22)Na and (125)I-albumin transit kinetics
      were monitored on-line with gamma detectors placed around the lung and the
      perfusate reservoir. [(3)H]mannitol was measured by repetitive counting of
      perfusion fluid samples. Volume of the alveolar epithelial lining fluid was
      estimated with bronchoalveolar lavage with sodium-free isosmolar mannitol
      solutions. Sodium clearance rate was -2.2 +/- 0.3%/min. This rate was
      significantly reduced by preadministration of ouabain/amiloride and enhanced by
      pretreatment with aerosolized terbutaline. The (125)I-albumin clearance rate was 
      0.40 +/- 0.05%/min. The appearance of [(3)H]mannitol in the perfusate was not
      influenced by ouabain/amiloride or terbutaline but was markedly enhanced by
      pretreatment with aerosolized protamine. An epithelial lining fluid volume of
      1.22 +/- 0.21 ml was calculated in control lungs. Fluid absorption rate was 1.23
      microl x g lung weight(-1) x min(-1), which was blunted after pretreatment with
      ouabain/amiloride. We conclude that alveolar tracer loading by aerosolization is
      a feasible technique to assess alveolar epithelial barrier properties in aerated
      lungs. Data on active and passive sodium flux, paracellular solute transit, and
      net fluid absorption correspond well to those in previous studies in fluid-filled
      lungs; however, albumin clearance rates were markedly higher in the currently
      investigated aerated lungs.

PMID- 11290514
TI  - Hyperoxia upregulates the NO pathway in alveolar macrophages in vitro: role of AP
      1 and NF-kappaB.
AB  - The inducible nitric oxide (NO) synthase gene in alveolar macrophages (AMs) is a
      stress response gene that may contribute to tissue injury in the lung after
      respiration with high O(2) concentrations through extensive production of NO. In
      this study, we investigated the influence of hyperoxia on the NO pathway in rat
      AMs in vitro, its regulation by the transcription factors nuclear factor (NF)
      kappaB and activator protein (AP)-1, and the role of reactive oxygen species
      (ROS). AMs were treated with lipopolysaccharide (LPS) and/or interferon (IFN)
      gamma and incubated under 21 or 85% O(2). Stimulation with LPS and IFN-gamma led
      to induction of the NO pathway that was further upregulated by hyperoxia. The
      binding activity of NF-kappaB, in contrast to that of AP-1, was activated on
      stimulation with LPS and IFN-gamma, and both were further increased under
      hyperoxia. The antioxidants pyrrolidine dithiocarbamate and N-acetyl-L-cysteine
      inhibited intracellular ROS production and the NO pathway under both normoxic and
      hyperoxic conditions but had diverse effects on the transcription factors. The
      results presented here indicate that hyperoxia can upregulate the NO pathway in
      stimulated AMs through increased production of intracellular ROS and activation
      of NF-kappaB and AP-1.

PMID- 11290515
TI  - Role of ecNOS-derived NO in mediating TNF-induced endothelial barrier
      dysfunction.
AB  - We tested the hypothesis that endothelial cell nitric oxide synthase (ecNOS)
      mediates the tumor necrosis factor (TNF)-alpha-induced increase in nitric oxide
      (NO) and albumin permeability in pulmonary microvessel endothelial monolayers
      (PEM). PEM lysates were analyzed for ecNOS mRNA (RT-PCR), ecNOS protein (Western
      immunoblot), NO levels (NO, the oxidation product of NO), and barrier function
      (albumin clearance rate). PEM were incubated with TNF (50 ng/ml) for 0.5, 2, 4,
      and 24 h. TNF induced a decrease in ecNOS mRNA at 2, 4, and 24 h. TNF induced an
      acute (0.5 h) increase followed by a protracted decrease (4-24 h) in ecNOS
      protein levels. The other NOS isotypes, inducible and brain NOS, could not be
      detected in the PEM using RT-PCR and Western blot assay. ecNOS antisense
      oligonucleotide decreased ecNOS protein, which prevented the increase in NO and
      albumin permeability at TNF-4 h. Spermine-NONOATE, the NO agonist, ablated the
      protective effect of ecNOS antisense oligonucleotide on albumin permeability in
      response to TNF-4 h. However, ecNOS antisense oligonucleotide had no effect on
      the TNF-induced increase in albumin permeability at 24 h despite prevention of
      the increase in NO. The data indicate that the isotype ecNOS mediates generation
      of NO and the acute (i.e., 4 h) barrier dysfunction; however, the prolonged
      (i.e., 24 h) increase in the TNF-induced increase in endothelial permeability is
      independent of NO.

PMID- 11290516
TI  - Nitric oxide decreases lung liquid production via guanosine 3',5'-cyclic
      monophosphate.
AB  - We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid
      production (J(v)) in chronically instrumented fetal sheep. Forty-five studies
      were done in which J(v) was measured by a tracer dilution technique. Left
      pulmonary arterial flow (Q(lpa)) was measured by a Doppler flow probe. There were
      two series of experiments. In the first, we gave 8-bromo-cGMP, a cGMP analog, by
      either the pulmonary vascular or intraluminal route; in the second, we used
      agents to inhibit or enhance endogenous cGMP activity. When infused directly into
      the pulmonary circulation, 8-bromo-cGMP significantly increased Q(lpa) but had no
      effect on J(v). Conversely, when instilled into the lung liquid, 8-bromo-cGMP had
      no effect on Q(lpa) but significantly reduced J(v). Inhibition of guanylate
      cyclase activity with methylene blue totally blocked, whereas phosphodiesterase
      inhibition with Zaprinast significantly enhanced, the effect of instilled NO on
      J(v). Thus the reduction in lung liquid caused by NO appears to be mediated by
      cGMP, perhaps through a direct effect on the pulmonary epithelium.

PMID- 11290517
TI  - Responsiveness of canine bronchial vasculature to excitatory stimuli and to
      cooling.
AB  - Changes in bronchial vascular tone, in part due to cooling during ventilation,
      may contribute to altered control of airflow during airway inflammation, asthma,
      and exercise-induced bronchoconstriction. We investigated the responses of canine
      bronchial vasculature to excitatory stimuli and cooling. Electrical stimulation
      evoked contractions in only some (8 of 88) tissues; these were phentolamine
      sensitive and augmented by N(omega)-nitro-L-arginine. However, sustained
      contractions were evoked in all tissues by phenylephrine [concentration evoking a
      half-maximal response (EC(50)) approximately 2 microM] or the thromboxane A(2)
      mimetic U-46619 (EC(50) approximately 5 nM) and less so by beta,gamma-methylene
      ATP or histamine. Cooling to room temperature markedly suppressed ( approximately
      75%) adrenergic responses but had no significant effect against U-46619
      responses. Adrenergic responses, but not those to U-46619, were accompanied by an
      increase in intracellular Ca(2+) concentration. Chelerythrine (protein kinase C
      antagonist) markedly antagonized adrenergic responses (mean maxima reduced 39% in
      artery and 86% in vein) but had no significant effect against U-46619, whereas
      genistein (a nonspecific tyrosine kinase inhibitor) essentially abolished
      responses to both agonists. We conclude that cooling of the airway wall
      dramatically interferes with adrenergic control of bronchial perfusion but has
      little effect on thromboxane-mediated vasoconstriction.

PMID- 11290518
TI  - Deformation-induced lipid trafficking in alveolar epithelial cells.
AB  - Mechanical ventilation with a high tidal volume results in lung injury that is
      characterized by blebbing and breaks both between and through alveolar epithelial
      cells. We developed an in vitro model to simulate ventilator-induced deformation
      of the alveolar basement membrane and to investigate, in a direct manner,
      epithelial cell responses to deforming forces. Taking advantage of the novel
      fluorescent properties of BODIPY lipids and the fluorescent dye FM1-43, we have
      shown that mechanical deformation of alveolar epithelial cells results in lipid
      transport to the plasma membrane. Deformation-induced lipid trafficking (DILT)
      was a vesicular process, rapid in onset, and was associated with a large increase
      in cell surface area. DILT could be demonstrated in all cells; however, only a
      small percentage of cells developed plasma membrane breaks that were reversible
      and nonlethal. Therefore, DILT was not only involved in site-directed wound
      repair but might also have served as a cytoprotective mechanism against plasma
      membrane stress failure. This study suggests that DILT is a regulatory mechanism
      for membrane trafficking in alveolar epithelia and provides a novel biological
      framework within which to consider alveolar deformation injury and repair.

PMID- 11290519
TI  - Neutrophil defensins mediate acute inflammatory response and lung dysfunction in
      dose-related fashion.
AB  - High concentrations of neutrophil defensins from airway and blood have been
      reported in patients with inflammatory lung diseases, but their exact role is
      unclear. We investigated the direct effect of defensins on the lungs of mice.
      Intratracheal instillation of purified defensins (5-30 mg/kg) induced a
      progressive reduction in peripheral arterial O(2) saturation, increased lung
      permeability, and enhanced the lung cytochrome c content. These indexes of acute
      lung dysfunction were associated with an increased total cell number and a
      significant neutrophil influx into the lung [5.1 +/- 0.04% in control vs. 48.6 +/
      12.7% in the defensin (30 mg/kg) group, P < 0.05]. Elastase concentrations in
      the bronchoalveolar lavage (BAL) fluids increased from 38 +/- 11 ng/ml (control)
      to 80 +/- 4 ng/ml (defensins, P < 0.05). Five hours after defensin instillation,
      concentrations of tumor necrosis factor-alpha and macrophage inflammatory protein
      2 in BAL fluid were significantly increased. High levels of monocyte
      chemoattractant protein-1 in BAL fluid and plasma were also found after defensin
      stimulation. We conclude that intratracheal instillation of defensins causes
      acute lung inflammation and dysfunction, suggesting that high concentrations of
      defensins in the airways may play an important role in the pathogenesis of
      inflammatory lung diseases.

PMID- 11290520
TI  - p38 MAP kinase negatively regulates cyclin D1 expression in airway smooth muscle
      cells.
AB  - We have demonstrated that platelet-derived growth factor (PDGF) stimulates p38
      mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes,
      suggesting that p38 is involved in growth regulation. We therefore examined
      whether p38 regulates expression of cyclin D1, a G(1) cyclin required for cell
      cycle traversal. The chemical p38 inhibitors SB-202190 and SB-203580 each
      increased basal and PDGF-induced cyclin D1 promoter activity and protein
      abundance. Overexpression of a dominant negative allele of MAP kinase kinase-3
      (MKK3), an upstream activator of p38alpha, had similar effects. Conversely,
      active MKK3 and MKK6, both of which increase p38alpha activity, each decreased
      transcription from the cyclin D1 promoter. Together, these data demonstrate that
      p38 negatively regulates cyclin D1 expression. We tested whether p38 regulates
      cyclin D1 expression via inhibition of extracellular signal-regulated kinase
      (ERK) activation. Chemical inhibitors of p38 induced modest ERK phosphorylation
      and activation. However, dominant negative MKK3 was insufficient to activate ERK,
      and active MKK3 and MKK6 did not attenuate platelet-derived growth factor
      mediated ERK activation. These data are consistent with the notion that p38alpha
      negatively regulates cyclin D1 expression via an ERK-independent pathway.

PMID- 11290521
TI  - EETs relax airway smooth muscle via an EpDHF effect: BK(Ca) channel activation
      and hyperpolarization.
AB  - Epoxyeicosatrienoic acids (EETs) are produced from arachidonic acid via the
      cytochrome P-450 epoxygenase pathway. EETs are able to modulate smooth muscle
      tone by increasing K(+) conductance, hence generating hyperpolarization of the
      tissues. However, the molecular mechanisms by which EETs induce smooth muscle
      relaxation are not fully understood. In the present study, the effects of EETs on
      airway smooth muscle (ASM) were investigated using three electrophysiological
      techniques. 8,9-EET and 14,15-EET induced concentration-dependent relaxations of
      the ASM precontracted with a muscarinc agonist (carbamylcholine chloride), and
      these relaxations were partly inhibited by 10 nM iberiotoxin (IbTX), a specific
      large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel blocker. Moreover, 3
      microM 8,9- or 14,15-EET induced hyperpolarizations of -12 +/- 3.5 and -16 +/- 3
      mV, with EC(50) values of 0.13 and 0.14 microM, respectively, which were either
      reversed or blocked on addition of 10 nM IbTX. These results indicate that BK(Ca)
      channels are involved in hyperpolarization and participate in the relaxation of
      ASM. In addition, complementary experiments demonstrated that 8,9- and 14,15-EET
      activate reconstituted BK(Ca) channels at low free Ca(2+) concentrations without
      affecting their unitary conductance. These increases in channel activity were
      IbTX sensitive and correlated well with the IbTX-sensitive hyperpolarization and
      relaxation of ASM. Together these results support the view that, in ASM, the EETs
      act through an epithelium-derived hyperpolarizing factorlike effect.

PMID- 11290522
TI  - Cdc42, but not RhoA, regulates cyclin D1 expression in bovine tracheal myocytes.
AB  - We previously demonstrated that Rac1 increased cyclin D1 promoter activity in an
      extracellular signal-regulated kinase (ERK)-independent, antioxidant-sensitive
      manner. Here, we examined the regulation of cyclin D1 expression by Cdc42 and
      RhoA. Overexpression of active Cdc42, but not of RhoA, induced transcription from
      the cyclin D1 promoter. Furthermore, dominant negative Cdc42, but not RhoA,
      attenuated platelet-derived growth factor-mediated activation of the cyclin D1
      promoter. Overexpression of active Cdc42 increased cyclin D1 protein abundance in
      COS cells. Cdc42-induced cyclin D1 promoter activation was independent of ERK as
      evidenced by insensitivity to PD-98059, an inhibitor of mitogen-activated protein
      kinase/ERK kinase (MEK). Furthermore, Cdc42 was neither sufficient nor required
      for activation of ERK. Similar to Rac1-induced cyclin D1 expression, pretreatment
      with the antioxidants catalase and ebselen inhibited Cdc42-mediated transcription
      from the cyclin D1 promoter. Finally, like Rac1, active Cdc42 induced
      transactivation of the cyclin D1 promoter cAMP response element binding
      protein/activating transcription factor-2 binding site. Together, these data
      suggest that in airway smooth muscle cells, Cdc42 and Rac1 share a common
      signaling pathway to cyclin D1 promoter activation.

PMID- 11290523
TI  - Regulation of endothelial cell barrier function by calcium/calmodulin-dependent
      protein kinase II.
AB  - Thrombin-induced endothelial cell barrier dysfunction is tightly linked to Ca(2+)
      dependent cytoskeletal protein reorganization. In this study, we found that
      thrombin increased Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II)
      activities in a Ca(2+)- and time-dependent manner in bovine pulmonary endothelium
      with maximal activity at 5 min. Pretreatment with KN-93, a specific CaM kinase II
      inhibitor, attenuated both thrombin-induced increases in monolayer permeability
      to albumin and decreases in transendothelial electrical resistance (TER). We next
      explored potential thrombin-induced CaM kinase II cytoskeletal targets and found
      that thrombin causes translocation and significant phosphorylation of nonmuscle
      filamin (ABP-280), which was attenuated by KN-93, whereas thrombin-induced myosin
      light chain phosphorylation was unaffected. Furthermore, a cell-permeable N
      myristoylated synthetic filamin peptide (containing the COOH-terminal CaM kinase
      II phosphorylation site) attenuated both thrombin-induced filamin phosphorylation
      and decreases in TER. Together, these studies indicate that CaM kinase II
      activation and filamin phosphorylation may participate in thrombin-induced
      cytoskeletal reorganization and endothelial barrier dysfunction.

PMID- 11290524
TI  - Synexin and GTP increase surfactant secretion in permeabilized alveolar type II
      cells.
AB  - We have previously suggested that synexin (annexin VII), a Ca(2+)-dependent
      phospholipid binding protein, may have a role in surfactant secretion, since it
      promotes membrane fusion between isolated lamellar bodies (the surfactant
      containing organelles) and plasma membranes. In this study, we investigated
      whether exogenous synexin can augment surfactant phosphatidylcholine (PC)
      secretion in synexin-deficient lung epithelial type II cells. Isolated rat type
      II cells were cultured for 20-22 h with [(3)H]choline to label cellular PC. The
      cells were then treated with beta-escin, which forms pores in the cell membrane
      and releases cytoplasmic proteins including synexin. These cells, however,
      retained lamellar bodies. The permeabilized type II cells were evaluated for PC
      secretion during a 30-min incubation. Compared with PC secretion under basal
      conditions, the presence of Ca(2+) (up to 10 microM) did not increase PC
      secretion. In the presence of 1 microM Ca(2+), synexin increased PC secretion in
      a concentration-dependent manner, which reached a maximum at approximately 5
      microg/ml synexin. The secretagogue effect of synexin was abolished when synexin
      was inactivated by heat treatment (30 min at 65 degrees C) or by treatment with
      synexin antibodies. GTP or its nonhydrolyzable analog beta:gamma-imidoguanosine
      5'-triphosphate also increased PC secretion in permeabilized type II cells. The
      PC secretion was further increased in an additive manner when a maximally
      effective concentration of synexin was added in the presence of 1 mM GTP,
      suggesting that GTP acts by a synexin-independent mechanism to increase membrane
      fusion. Thus our results support a direct role for synexin in surfactant
      secretion. Our study also suggests that membrane fusion during surfactant
      secretion may be mediated by two independent mechanisms.

PMID- 11290525
TI  - Release of biologically active TGF-beta from airway smooth muscle cells induces
      autocrine synthesis of collagen.
AB  - In severe or chronic asthma, there is an increase in airway smooth muscle cell
      (ASMC) mass as well as an increase in connective tissue proteins in the smooth
      muscle layer of airways. Transforming growth factor-beta (TGF-beta) exists in
      three isoforms in mammals and is a potent regulator of connective tissue protein
      synthesis. Using immunohistochemistry, we had previously demonstrated that ASMCs
      contain large quantities of TGF-beta1-3. In this study, we demonstrate that
      bovine ASMC-derived TGF-beta associates with the TGF-beta latency binding protein
      1 (LTBP-1) expressed by the same cells. The TGF-beta associated with LTBP-1
      localizes TGF-beta extracellularly. Furthermore, plasmin, a serine protease,
      regulates the secretion of a biologically active form of TGF-beta by ASMCs as
      well as the release of extracellular TGF-beta. The biologically active TGF-beta
      released by plasmin induces ASMCs to synthesize collagen I in an autocrine
      manner. The autocrine induction of collagen expression by ASMCs may contribute to
      the irreversible fibrosis and remodeling seen in the airways of some asthmatics.

PMID- 11290526
TI  - Activation of class IA PI3K stimulates DNA synthesis in human airway smooth
      muscle cells.
AB  - The precise mechanisms that regulate increases in airway smooth muscle (ASM) mass
      in asthma are unknown. This study determined whether class IA
      phosphatidylinositol 3-kinase (PI3K) is sufficient to stimulate DNA synthesis and
      characterized the PI3K isoforms expressed in human ASM cells. ASM cells express
      class IA, II, and III PI3K but not class IB. Because thrombin induces ASM cell
      proliferation, we investigated whether thrombin can stimulate class IA PI3K.
      Transient transfection of ASM cells with hemagglutinin-tagged p85 PI3K followed
      by immunostaining revealed that in quiescent cells, p85 was expressed diffusely
      in the cytoplasm and after stimulation with thrombin p85 translocated to the cell
      membrane. Microinjection of ASM cells with a dominant negative class IA PI3K
      inhibited thrombin-induced DNA synthesis by 30% and epidermal growth factor (EGF)
      or serum-induced DNA synthesis by 13 and 28%, respectively (P < 0.05 by chi(2)
      analysis). In parallel experiments, transfection or microinjection of cells with
      constitutively active PI3K markedly increased DNA synthesis in transfected cells
      10.5-fold and in microinjected cells 12.7-fold (P < 0.05 by chi(2) analysis)
      compared with cells transfected or microinjected with control plasmid.
      Interestingly, constitutively active PI3K augmented EGF-induced DNA synthesis but
      had little effect on that induced by serum or thrombin in ASM cells.
      Collectively, these data suggest that class IA PI3K is activated by thrombin and
      is sufficient to induce ASM cell growth.

PMID- 11290527
TI  - ERK activation and mitogenesis in human airway smooth muscle cells.
AB  - Asthmatic airways are characterized by an increase in smooth muscle mass, due
      mainly to hyperplasia. Many studies suggest that extracellular signal-regulated
      kinases 1 and 2 (ERK1 and ERK2, respectively), one group of the mitogen-activated
      protein (MAP) kinase superfamily, play a key role in the signal transduction
      pathway leading to cell proliferation. PGE(2) and forskolin inhibited mitogen
      induced ERK activation. Inhibition of MAP kinase kinases 1 and 2 (MEK1 and MEK2,
      respectively), which are upstream from ERK, with the specific MEK inhibitor U
      0126 blocked both cell proliferation and ERK activation. In addition, U-0126
      inhibited mitogen-induced activation of p90 ribosomal S6 kinase and expression of
      c-Fos and cyclin D1, all of which are downstream from ERK in the signaling
      cascade that leads to cell proliferation. Antisense oligodeoxynucleotides
      directed to ERK1 and -2 mRNAs reduced ERK protein and cell proliferation. These
      results indicate that ERK is required for human airway smooth muscle cell
      proliferation. Thus targeting the control of ERK activation may provide a new
      therapeutic approach for hyperplasia seen in asthma.

PMID- 11290528
TI  - Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching
      morphogenesis.
AB  - Bone morphogenetic protein-4 (BMP-4) is a key morphogen for embryonic lung
      development that is expressed at high levels in the peripheral epithelium, but
      the mechanisms that modulate BMP-4 function in early mouse lung branching
      morphogenesis are unclear. Here, we studied the BMP-4 antagonist Gremlin, which
      is a member of the DAN family of BMP antagonists that can bind and block BMP-2/4
      activity. The expression level of gremlin in embryonic mouse lungs is highest in
      the early embryonic pseudoglandular stage [embryonic days (E) 11.5-14.5] and is
      reduced during fetal lung maturation (E18.5 to postnatal day 1). In situ
      hybridization indicates that gremlin is diffusely expressed in peripheral lung
      mesenchyme and epithelium, but relatively high epithelial expression occurs in
      branching buds at E11.5 and in large airways after E16.5. In E11.5 lung organ
      culture, we found that exogenous BMP-4 dramatically enhanced peripheral lung
      epithelial branching morphogenesis, whereas reduction of endogenous gremlin
      expression with antisense oligonucleotides achieved the same gain-of-function
      phenotype as exogenous BMP-4, including increased epithelial cell proliferation
      and surfactant protein C expression. On the other hand, adenoviral overexpression
      of gremlin blocked the stimulatory effects of exogenous BMP-4. Therefore, our
      data support the hypothesis that Gremlin is a physiologically negative regulator
      of BMP-4 in lung branching morphogenesis.

PMID- 11290529
TI  - Endothelin B receptor deficiency potentiates ET-1 and hypoxic pulmonary
      vasoconstriction.
AB  - Endothelin (ET)-1 contributes to the regulation of pulmonary vascular tone by
      stimulation of the ET(A) and ET(B) receptors. Although activation of the ET(A)
      receptor causes vasoconstriction, stimulation of the ET(B) receptors can elicit
      either vasodilation or vasoconstriction. To examine the physiological role of the
      ET(B) receptor in the pulmonary circulation, we studied a genetic rat model of
      ET(B) receptor deficiency [transgenic(sl/sl)]. We hypothesized that deficiency of
      the ET(B) receptor would predispose the transgenic(sl/sl) rat lung circulation to
      enhanced pulmonary vasoconstriction. We found that the lungs of transgenic(sl/sl)
      rats are ET(B) deficient because they lack ET(B) mRNA in the pulmonary
      vasculature, have minimal ET(B) receptors as determined with an ET-1 radioligand
      binding assay, and lack ET-1-mediated pulmonary vasodilation. The
      transgenic(sl/sl) rats have higher basal pulmonary arterial pressure and
      vasopressor responses to brief hypoxia or ET-1 infusion. Plasma ET-1 levels are
      elevated and endothelial nitric oxide synthase protein content and nitric oxide
      production are diminished in the transgenic(sl/sl) rat lung. These findings
      suggest that the ET(B) receptor plays a major physiological role in modulating
      resting pulmonary vascular tone and reactivity to acute hypoxia. We speculate
      that impaired ET(B) receptor activity can contribute to the pathogenesis of
      pulmonary hypertension.

PMID- 11290530
TI  - Dual signaling by the alpha(v)beta(3)-integrin activates cytosolic PLA(2) in
      bovine pulmonary artery endothelial cells.
AB  - Vitronectin, which ligates the alpha(v)beta(3)-integrin, increases both lung
      capillary permeability and lung endothelial Ca(2+). In stable monolayers of
      bovine pulmonary artery endothelial cells (BPAECs) viewed with confocal
      microscopy, multimeric vitronectin aggregated the apically located
      alpha(v)beta(3)-integrin. This caused arachidonate release that was inhibited by
      pretreating the monolayers with the anti-alpha(v)beta(3) monoclonal antibody
      (MAb) LM609. No inhibition occurred in the presence of the isotypic MAb PIF6,
      which recognizes the integrin alpha(v)beta(5). Vitronectin also caused membrane
      translocation and phosphorylation of cytosolic phospholipase A(2) (cPLA(2)) as
      well as tyrosine phosphorylation of the mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated kinase (ERK) 2. The cPLA(2) inhibitor arachidonyl
      trifluoromethylketone, the tyrosine kinase inhibitor genistein, and the MAPK
      kinase inhibitor PD-98059 all blocked the induced arachidonate release. PD-98059
      did not inhibit the increase of cytosolic Ca(2+) or cPLA(2) translocation,
      although it blocked tyrosine phosphorylation of ERK2. Moreover, although the
      intracellular Ca(2+) chelator MAPTAM also inhibited arachidonate release, it did
      not inhibit tyrosine phosphorylation of ERK2. These findings indicate that
      ligation of apical alpha(v)beta(3) in BPAECs caused ERK2 activation and an
      increase of intracellular Ca(2+), both conjointly required for cPLA(2) activation
      and arachidonate release. This is the first instance of a tyrosine
      phosphorylation-initiated "two-hit" signaling pathway that regulates an integrin
      induced proinflammatory response.

PMID- 11290531
TI  - Isolation of pulmonary interstitial fluid in rabbits by a modified wick
      technique.
AB  - Interstitial fluid protein concentration (C(protein)) values in perivascular and
      peribronchial lung tissues were never simultaneously measured in mammals; in this
      study, perivascular and peribronchial interstitial fluids were collected from
      rabbits under control conditions and rabbits with hydraulic edema or lesional
      edema. Postmortem dry wicks were implanted in the perivascular and peribronchial
      tissues; after 20 min, the wicks were withdrawn and the interstitial fluid was
      collected to measure C(protein) and colloid osmotic pressure. Plasma,
      perivascular, and peribronchial C(protein) values averaged 6.4 +/- 0.7 (SD), 3.7
      +/- 0.5, and 2.4 +/- 0.7 g/dl, respectively, in control rabbits; 4.8 +/- 0.7, 2.5
      +/- 0.6, and 2.4 +/- 0.4 g/dl, respectively, in rabbits with hydraulic edema; and
      5.1 +/- 0.3, 4.3 +/- 0.4 and 3.3 +/- 0.6 g/dl, respectively, in rabbits with
      lesional edema. Contamination of plasma proteins from microvascular lesions
      during wick insertion was 14% of plasma C(protein). In control animals, pulmonary
      interstitial C(protein) was lower than previous estimates from pre- and postnodal
      pulmonary lymph; furthermore, although the interstitium constitutes a continuum
      within the lung parenchyma, regional differences in tissue content seem to exist
      in the rabbit lung.

PMID- 11290533
TI  - Glucose, VEGF-A, and diabetic complications.

PMID- 11290534
TI  - A case of tumor betrayal: biphasic effects of TIMP-1 on Burkitt's lymphoma.

PMID- 11290535
TI  - Induction of megakaryocytic differentiation in primary human erythroblasts: a
      physiological basis for leukemic lineage plasticity.
AB  - In myelodysplasias and acute myeloid leukemias, abnormalities in erythroid
      development often parallel abnormalities in megakaryocytic development.
      Erythroleukemic cells in particular have been shown to possess the potential to
      undergo megakaryocytic differentiation in response to a variety of stimuli.
      Whether or not such lineage plasticity occurs as a consequence of the leukemic
      phenotype has not previously been addressed. In this study, highly purified
      primary human erythroid progenitors were subjected to stimuli known to induce
      megakaryocytic differentiation in erythroleukemic cells. Remarkably, the primary
      erythroid progenitors rapidly responded with morphological and immunophenotypic
      evidence of megakaryocytic differentiation, equivalent to that seen in
      erythroleukemic cells. Even erythroblasts expressing high levels of hemoglobin
      manifested partial megakaryocytic differentiation. These results indicate that
      the lineage plasticity observed in erythroleukemic cells reflects an intrinsic
      property of cells in the erythroid lineage rather than an epiphenomenon of
      leukemic transformation.

PMID- 11290536
TI  - Hyperglycemia-induced vasculopathy in the murine conceptus is mediated via
      reductions of VEGF-A expression and VEGF receptor activation.
AB  - Major congenital malformations, including those affecting the cardiovascular
      system, remain the leading cause of mortality and morbidity in infants of
      diabetic mothers. Interestingly, targeted mutations of several genes (including
      VEGF and VEGF receptors) and many teratogenic agents (including excess D-glucose)
      that give rise to embryonic lethal phenotypes during organogenesis are associated
      with a failure in the formation and/or maintenance of a functional vitelline
      circulation. Given the similarities in the pathology of the abnormal vitelline
      circulation in many of these conditions, we hypothesized that the hyperglycemic
      insult present in diabetes could cause the resultant abnormalities in the
      vitelline circulation by affecting VEGF/VEGF receptor signaling pathway(s). In
      this study we report that hyperglycemic insult results in reduced levels of VEGF
      A in the conceptus, which in turn, leads to abnormal VEGF receptor signaling,
      ultimately resulting in embryonic (vitelline) vasculopathy. These findings and
      our observation that addition of exogenous rVEGF-A(165) within a defined
      concentration range blunts the hyperglycemia-induced vasculopathy in the
      conceptus support the concept that VEGF levels can be modulated by glucose
      levels. In addition, these findings may ultimately lead to novel therapeutic
      approaches for the treatment of selected congenital cardiovascular abnormalities
      associated with diabetes.

PMID- 11290537
TI  - Tissue inhibitor of metalloproteinase-1 alters the tumorigenicity of Burkitt's
      lymphoma via divergent effects on tumor growth and angiogenesis.
AB  - Epstein-Barr virus (EBV)-positive Burkitt's lymphoma cells and EBV-infected B
      cells elicit humoral factors that inhibit tumor-induced angiogenesis, resulting
      in tumor necrosis and regression. Of the chemokine factors identified in
      association with this growth behavior, none have induced complete tumor
      regression. We have previously identified tissue inhibitors of metalloproteinase
      (TIMP)-1 in various B cell lymphoma cell lines. Here we show that induction of
      TIMP-1 expression in an EBV-negative Burkitt's lymphoma cell line results in a
      biphasic, in vivo tumor growth pattern in the nude mouse that is essentially
      identical to EBV-positive Burkitt's lymphoma cell lines. The initial effect of
      TIMP-1 is to enhance tumor growth, consistent with the reported anti-apoptotic
      effect of TIMP-1 on B cell growth. Tumor necrosis and regression then follow the
      initial period of rapid, increased tumor growth. Only microscopic foci of
      residual, proliferating tumor cells are observed on biopsy of the tumor site.
      This latter effect is mediated by TIMP-1 inhibition of an angiogenic response
      within the developing tumor mass, as demonstrated by immunostaining and
      microvessel counts. These findings suggest that TIMP-1 is an important mediator
      of the in vivo growth properties of EBV-positive Burkitt's lymphoma.

PMID- 11290538
TI  - Growth hormone receptor is expressed in human breast cancer.
AB  - Several clinical observations and experimental studies indicate that pituitary
      hormones, including growth hormone, play a role in the development of human
      breast cancer. We analyzed 48 human breast carcinomas using reverse transcription
      polymerase chain reaction, immunohistochemistry, and Western blotting techniques
      to assess growth hormone receptor expression. In 17 of these cases, adjacent
      normal breast tissue was similarly analyzed. These analyses revealed that growth
      hormone receptor (GHR) is expressed in human breast cancer and appears to be up
      regulated compared to adjacent normal breast tissue. GHR expression correlated
      inversely with tumor grade and MIB-1 index. Progesterone receptor expression
      correlated positively with GHR expression. These findings, along with our
      observation of GHR expression in breast cancer stromal cells and previous reports
      of local production of growth hormone in breast carcinoma, suggest that GHR
      mediated signaling pathways are involved in the development of human breast
      cancer, possibly via autocrine or paracrine mechanisms.

PMID- 11290539
TI  - The neurofibromatosis type 2 gene is mutated in perineurial cell tumors: a
      molecular genetic study of eight cases.
AB  - Perineurial cell tumors (PNTs) are rare neoplasms derived from or showing
      differentiation toward specialized lining cells of the nerve sheath, the
      perineurial cells. In this study, we have evaluated neurofibromatosis type 2
      (NF2) gene alterations in eight PNTs using archival formaldehyde-fixed, paraffin
      embedded tissue. Two conventional soft-tissue PNTs from the upper back and chest
      wall, one retiform soft tissue variant from the scapular region, and five
      sclerosing PNTs from the fingers and palm were studied. All cases showed
      histological features of PNTs, and the neoplastic cells were positive for
      epithelial membrane antigen and negative for S100 protein. The coding sequences
      (exons 1 to 15) of the NF2 gene were polymerase chain reaction (PCR) amplified
      and evaluated for mutations by direct sequencing of the PCR products. Five NF2
      point mutations, two in the 5'-untranslated region (UTR) and three in exons 3, 6,
      and 8, were identified in four of eight cases (50%) studied. Exon mutations
      resulted in changes of predicted amino acids sequences: Asp-->Asn at codon 83,
      Glu-->Asp at codon 182, and Leu-->Val at codon 241. In two cases (one with a
      missense mutation in codon 241), the same point mutation in the 5'-UTR at the
      nucleotide position 8958 was identified. A loss of heterozygosity (LOH) study was
      performed in three cases. LOH at the NF2 locus was found in one case with a
      mutation in the 5'-UTR. However, in another case with exon 8 and 5'-UTR
      mutations, deletion of one allele of the NF2 gene was previously documented by
      fluorescence in situ hybridization. The coexistence of NF2 gene mutations and LOH
      at the NF2 locus indicates that the NF2 tumor suppressor gene is altered in PNTs
      by the two-hit mechanism.

PMID- 11290540
TI  - Comparative genome-scale analysis of gene expression profiles in T cell lymphoma
      cells during malignant progression using a complementary DNA microarray.
AB  - Using a cDNA microarray, we compared the expression of approximately 8000 genes
      between two unique, clonally related T cell lines derived from different stages
      of a progressive T cell lymphoma involving skin. A total of 180 genes was found
      to be differentially expressed at the RNA level by a factor of fivefold or
      greater. Compared with the cells from the earlier, clinically indolent stage of
      the lymphoma, 56 genes were up-regulated, whereas 124 genes were down-regulated
      in the cells from the advanced, clinically aggressive stage lymphoma. The
      functions of approximately 65% of these genes are currently unknown. The 22 genes
      with a known function that were up-regulated in the advanced lymphoma cells
      included several genes involved in promotion of cell proliferation and survival
      as well as drug resistance. The 42 functionally characterized genes that were
      down-regulated in the advanced lymphoma cells included negative regulators of
      cell activation and cell cycle, and mediators of cell adhesion, apoptosis, and
      genome integrity. The differential expression identified by the cDNA microarray
      analysis was confirmed for selected genes by reverse transcription-polymerase
      chain reaction and Northern blotting. The identified differences in gene
      expression may be related to the differences in behavior between the early and
      advanced stages of the T cell lymphoma and point to directions for further
      investigations into mechanisms of lymphoma progression.

PMID- 11290542
TI  - Validation of tissue microarrays for immunohistochemical profiling of cancer
      specimens using the example of human fibroblastic tumors.
AB  - Tissue microarrays allow high-throughput molecular profiling of cancer specimens
      by immunohistochemistry. Phenotype information of sections from arrayed biopsies
      on a multitissue block needs to be representative of full sections, as protein
      expression varies throughout the entire tumor specimen. To validate the use of
      tissue microarrays for immunophenotyping, we studied a group of 59 fibroblastic
      tumors with variable protein expression patterns by immunohistochemistry for Ki
      67, p53, and the retinoblastoma protein (pRB). Data on full tissue sections were
      compared to the results of one, two, and three 0.6-mm core biopsies per tumor on
      a tissue array. Ki-67 and p53 staining was read as two categories (positive or
      negative). Concordance for this staining between tissue arrays with triplicate
      cores per tumor and full sections were 96 and 98%, respectively. For pRB staining
      was read as three categories (high, moderate, or negative), where concordance was
      91%. The use of three cores per tumor resulted in lower numbers of lost cases and
      lower nonconcordance with standard full sections as compared to one or two cores
      per tumor. Correlations between phenotypes and clinical outcome were not
      significantly different between full section and array-based analysis. Triplicate
      0.6-mm core biopsies sampled on tissue arrays provide a reliable system for high
      throughput expression profiling by immunohistochemistry when compared to standard
      full sections. Triplicate cores offer a higher rate of assessable cases and a
      lower rate of nonconcordant readings than one or two cores. Concordance of
      triplicate cores is high (96 to 98%) for two category distinction and decreases
      with the complexity of the phenotypes being analyzed (91%).

PMID- 11290541
TI  - Proliferating bile duct epithelial cells are a major source of connective tissue
      growth factor in rat biliary fibrosis.
AB  - Connective tissue growth factor (CTGF) is a downstream mediator of transforming
      growth factor-beta1 (TGF-beta1) and thus a potential target for antifibrotic
      treatment strategies. CTGF is up-regulated in disorders such as atherosclerosis,
      scleroderma, and fibrosis of kidneys and lungs. We investigated the
      temporospatial expression patterns of CTGF and TGF-beta1 mRNA in rat livers with
      acute fibrogenesis (after a single dose of CCl(4)) and with advanced fibrosis (6
      weeks after complete bile duct occlusion). Multiprobe ribonuclease protection
      assay revealed increasing TGF-beta1 and CTGF mRNA levels 6 hours after injection
      of CCl(4), with peak levels after 72 hours. In biliary fibrosis TGF-beta1 and
      CTGF mRNA levels increased fourfold and sevenfold, respectively (P: < 0.001). In
      situ hybridization combined with cell-specific markers revealed CTGF transcripts
      in desmin-positive cells after a single dose of carbon tetrachloride, whereas no
      transcripts were found in normal livers. In biliary fibrosis, however,
      proliferating bile duct epithelial cells were the predominant source of CTGF
      mRNA. We conclude that in rat liver fibrogenesis CTGF is up-regulated in close
      association with TGF-beta1 and that, contrary to a previous report, not solely
      hepatic stellate cells but activated bile duct epithelial cells are the main
      source of this profibrogenic factor.

PMID- 11290543
TI  - Detection of 1p and 19q loss in oligodendroglioma by quantitative microsatellite
      analysis, a real-time quantitative polymerase chain reaction assay.
AB  - The combined loss of chromosomes 1p and 19q has recently emerged as a genetic
      predictor of chemosensitivity in anaplastic oligodendrogliomas. Here, we describe
      a strategy that uses a novel method of real-time quantitative polymerase chain
      reaction, quantitative microsatellite analysis (QuMA), for the molecular analysis
      of 1p and 19q loss in oligodendrogliomas and oligoastrocytomas in archival
      routinely processed paraffin material. QuMA is performed on the ABI 7700 and
      based on amplifications of microsatellite loci that contain (CA)n repeats where
      the repeat itself is the target for hybridization by the fluorescently labeled
      probe. This single probe can therefore be used to determine copy number of
      microsatellite loci spread throughout the human genome. In genomic DNA prepared
      from paraffin-embedded brain tumor specimens, QuMA detected combined loss of 1p
      and 19q in 64% (21 of 32) of oligodendrogliomas and 67% (6 of 9) of
      oligoastrocytomas. We validate the use of QuMA as a reliable method to detect
      copy number by showing concordance between QuMA and fluorescence in situ
      hybridization at 37 of 45 chromosomal arms tested. These results indicate that
      QuMA is an accurate, high-throughput assay for the detection of copy number at
      multiple loci; as many as 31 loci of an individual tumor can be analyzed on a 96
      well plate in a single 2-hour run. In addition, it has advantages over standard
      allelic imbalance/loss of heterozygosity assays in that all loci are potentially
      informative, paired normal tissue is not required, and gain can be distinguished
      from loss. QuMA may therefore be a powerful molecular tool to expedite the
      genotypic analysis of human gliomas in a clinical setting for
      diagnostic/prognostic purposes.

PMID- 11290544
TI  - Macrophage-derived chemokine (MDC/CCL22) and CCR4 are involved in the formation
      of T lymphocyte-dendritic cell clusters in human inflamed skin and secondary
      lymphoid tissue.
AB  - Our previous study demonstrated formation of T cell-dendritic cell (DC) clusters
      in inflamed dermis of intraorally autotransplanted skin flaps. Such T cell-DC
      clusters are supposed to be important for close interactions between T cells and
      DCs including the specific antigen presentation. Here we show the involvement of
      the macrophage-derived chemokine (MDC/CCL22) and its specific receptor CC
      chemokine receptor 4 (CCR4) in the formation of T cell-DC clusters. Reverse
      transcriptase-polymerase chain reaction analysis revealed high levels of mRNA
      expression for MDC and CCR4 in inflamed skin and neck lymph nodes (LNs), but not
      in normal skin. Immunohistochemically, MDC(+) cells and CCR4(+) cells were mainly
      located within the T cell-DC clusters both in the dermis of inflamed skin and the
      T cell area of LNs. MDC(+) cells were identified to be DCs both in inflamed skin
      and LNs. The majority of CCR4(+) cells were CD4(+) T cells, accounting for
      approximately one-third of total CD4(+) T cells in the inflamed skin. Our data
      suggest that the MDC-CCR4 system plays an important role in the formation of T
      cell-DC clusters both in inflamed skin and LNs.

PMID- 11290545
TI  - Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by
      retinal detachment in vivo.
AB  - Apoptosis-inducing factor (AIF) is a novel mediator in apoptosis. AIF is a
      flavoprotein that is normally confined to the mitochondrial intermembrane space,
      yet translocates to the nucleus in several in vitro models of apoptosis. To
      investigate the role of AIF in the apoptotic process in vivo, we induced retinal
      detachment (RD) by subretinal injection of sodium hyaluronate, either in Brown
      Norway rats or in C3H mice. Apoptotic DNA fragmentation, as determined by
      terminal nick-end labeling, was most prominent 3 days after RD. The subcellular
      localization of AIF was examined by immunohistochemistry and immunoelectron
      microscopy. In normal photoreceptor cells, AIF was present in the mitochondrion
      rich inner segment. However, AIF was found in the nucleus after RD. Photoreceptor
      apoptosis developed similarly in C3H control mice, and in mice bearing the gld or
      lpr mutations, indicating that cell death occurs independently from the CD95/CD95
      ligand system. Both the mitochondrio-nuclear transition of AIF localization and
      the nuclear DNA fragmentation were inhibited by subretinal application of brain
      derived neurotrophic factor. To our knowledge, this is the first description of
      AIF relocalization occurring in a clinically relevant, in vivo model of
      apoptosis.

PMID- 11290546
TI  - Molecular determinants of ovarian cancer plasticity.
AB  - During development, the formation and remodeling of primary vascular networks
      occurs by vasculogenesis and angiogenesis. Recently, the term "vasculogenic
      mimicry" has been used by our laboratory and collaborators to reflect the
      embryonic-like ability of aggressive, but not nonaggressive, melanoma tumor cells
      to form a pattern of matrix-rich networks (containing channels) surrounding
      spheroids of tumor cells in three-dimensional culture, concomitant with their
      expression of vascular cell markers. Ovarian cancer is usually diagnosed as
      advanced stage disease in most patients when widespread metastases have already
      been established within the peritoneal cavity. In this study, we explored whether
      invasive ovarian carcinoma cells could engage in molecular vasculogenic mimicry
      reflected by their plasticity, compared with their normal cell counterparts. The
      data revealed that the invasive ovarian cancer cells, but not normal ovarian
      surface epithelial cells, formed patterned networks containing solid and hollow
      matrix channels when grown in three-dimensional cultures containing Matrigel or
      type I collagen, in the absence of endothelial cells or fibroblasts.
      Immunohistochemical analysis showed that matrix metalloproteinases (MMP)-1, -2,
      and -9, and MT1-MMP were discretely localized to these networks, and the
      formation of the networks was inhibited by treatment with MMP inhibitors.
      Furthermore, the RNase protection assay revealed the expression of multiple
      vascular cell-associated markers by the invasive ovarian cancer cells. In patient
      tumor sections from high-stage, high-grade ovarian cancers, 7 to 10% of channels
      containing red blood cells were lined by tumor cells. By comparison, all vascular
      areas in benign tumors and low-stage cancers were endothelial lined. These
      results may offer new insights and molecular markers for consideration in ovarian
      cancer diagnosis and treatment strategies based on molecular vascular mimicry by
      aggressive tumor cells.

PMID- 11290547
TI  - c-Myb and Bcl-x overexpression predicts poor prognosis in colorectal cancer:
      clinical and experimental findings.
AB  - The aim of this study was twofold: to assess the relationship between c-Myb and
      Bcl-x expression and to evaluate the prognostic significance of their expression
      in colorectal carcinoma (CRC) patients. Analysis of tumors from 91 CRC patients
      for expression of c-Myb and Bcl-x revealed a significant relationship between
      these two proteins. Kaplan-Meier's analysis showed an increased risk of relapse
      and death in patients whose tumor specimens displayed high c-Myb levels and Bcl-x
      positivity. Similar results were also observed excluding Dukes' D patients.
      Molecular analysis using three c-Myb-overexpressing LoVo clones indicated that c
      Myb overexpression was accompanied by up-regulation of Bcl-x(L) protein and mRNA.
      Tumors originating from these clones injected in nude mice were significantly
      larger than those formed in mice injected with parental or vector-transfected
      LoVo cells. Moreover, tumors derived from parental and control vector-transfected
      but not from c-Myb-overexpressing LoVo cells showed high frequency of apoptotic
      cells. These results provide direct evidence of an association between c-Myb and
      Bcl-x expression and suggest that expression of both molecules might be a useful
      prognostic marker in CRC.

PMID- 11290548
TI  - Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in
      vitro and in vivo.
AB  - Matriptase and its cognate, Kunitz-type serine protease inhibitor, HAI-1,
      comprise a newly characterized extracellular matrix-degrading protease system
      that may function as an epithelial membrane activator for other proteases and
      latent growth factors. Both enzyme and inhibitor have been detected in breast
      cancer cells, immortalized mammary epithelial cells, and human milk, but not in
      cultured fibroblasts nor in fibrosarcoma cells. To test the hypothesis that this
      system is expressed by normal breast epithelium, invasive breast cancers, and
      other cancers of an epithelial origin (carcinomas) but not in cancers of a
      mesenchymal origin, we have expanded our expression analysis of matriptase and
      HAI-1 in vitro and in vivo. Matriptase and HAI-1 were detected at the protein and
      mRNA levels both in hormone-dependent and hormone-independent cultured breast
      cancer cells, and this expression correlated with the expression of the
      epithelial markers E-cadherin or ZO-1. However, none of the breast cancer cell
      lines tested that express the mesenchymal marker vimentin express matriptase or
      HAI-1, consistent with an epithelial-selective expression of this system.
      Expression of matriptase, as determined by Western blot analysis, was observed in
      primary human breast, gynecological, and colon carcinomas, but not in stromal
      derived ovarian tumors and human sarcomas of various origins and histological
      grades. The epithelial-selective expression of matriptase and HAI-1 was further
      confirmed in human breast cancers by immunohistochemistry and in situ
      hybridization, where the expression of the protease and the inhibitor were found
      in the carcinoma cells and in surrounding normal breast epithelia. The expression
      of the matriptase/HAI-1 system by malignant epithelial cells in vivo suggests a
      possible role for this protease in multiple aspects of the pathophysiology of
      epithelial malignancy, including invasion and metastasis.

PMID- 11290549
TI  - Origin and structural evolution of the early proliferating oval cells in rat
      liver.
AB  - We have analyzed the histological changes in rat liver after 2
      acetylaminofluorene (AAF) administration. The data demonstrate that AAF-induced
      oval cells were preferentially generated by proliferation of the terminal biliary
      ductules that we suggest constitute the primary hepatic stem cell niche. The oval
      cells formed ductular structures, representing an extension of the canals of
      Hering. This histological organization provides continuous bile drainage of the
      hepatocytes and uninterrupted blood flow in the sinusoids. The oval cell ductules
      are surrounded by a continuous basement membrane that is intermittently disrupted
      by processes of stellate cells that form direct cell-cell contact with the oval
      cells. Although both AAF treatment and bile duct ligation results in
      proliferation of biliary epithelial cells, the mechanism(s) responsible for the
      proliferation of the biliary epithelium seems to differ in the two models. In
      contrast to the biliary proliferation stimulated by bile ligation, AAF-induced
      oval cell proliferation as well as the capacity of these cells to differentiate
      into hepatocytes, bile epithelial cells and possibly other cell lineages can be
      blocked by administration of dexamethasone.

PMID- 11290550
TI  - Heterogeneous vascular dependence of tumor cell populations.
AB  - Cells within a tumor are highly heterogeneous with respect to a wide range of
      genotypic and phenotypic characteristics. The latter include such properties as
      growth, survival, invasion, and metastasis. We asked whether the degree to which
      individual tumor cells rely on a tumor's vasculature might also be heterogeneous.
      By adapting an intravital Hoechst 33342 staining technique, we labeled and
      isolated tumor cells based on their relative proximity to perfused vessels.
      Because tumor regions distal to the vasculature are likely hypoxic, we examined
      cells deficient for hypoxia-inducible factor-1alpha (HIF-1alpha), a transcription
      factor that has been shown to mediate hypoxia-induced responses, including
      apoptosis. Despite reduced vascularization in HIF-1alpha-/- embryonic stem cell
      derived tumors, their growth in vivo was found to be accelerated relative to HIF
      1alpha+/+ tumor counterparts. We hypothesized that this paradoxical observation
      is because of decreased apoptotic rate, resulting in diminished vascular
      dependence of HIF-1alpha-/- cells. Analysis of heterogeneous tumors established
      from mixtures of HIF-1alpha+/+ with HIF-1alpha-/- cells revealed that the
      proportion of cells expressing wild-type HIF-1alpha was increased in perivascular
      areas and decreased in distal tumor regions. Thus, cells expressing HIF-1alpha
      were found to be highly dependent on proximity to blood vessels for their growth
      and survival in vivo, whereas cells that had lost HIF-1alpha expression were much
      less so. Heterogeneity in angiogenesis dependence was also observed among cell
      subpopulations isolated from human melanoma xenografts. This potential for
      selection of less vascular-dependent tumor cell variants throughout the course of
      disease progression may have important implications for the long-term efficacy of
      anti-angiogenic therapy.

PMID- 11290551
TI  - Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer.
AB  - Fas-associated phosphatase-1 (FAP-1) is a protein-tyrosine phosphatase that binds
      the cytosolic tail of Fas (Apo1, CD95), presumably regulating Fas-induced
      apoptosis. Elevations of FAP-1 protein levels in some tumor cell lines have been
      correlated with resistance to Fas-induced apoptosis. To explore the expression of
      FAP-1 in ovarian cancer cell lines and archival tumor specimens, mouse monoclonal
      and rabbit polyclonal antibodies were generated against a FAP-1 peptide and
      recombinant FAP-1 protein. These antibodies were used for immunoblotting,
      immunohistochemistry, and flow-cytometry analysis of FAP-1 expression in the Fas
      sensitive ovarian cancer lines HEY and BG-1, and in the Fas-resistant lines OVCAR
      3 FR and SK-OV-3. All methods demonstrated high levels of FAP-1 in the resistant
      lines OVCAR-3 FR and SK-OV-3, but not in the Fas-sensitive lines HEY and BG-1.
      Furthermore, levels of FAP-1 protein also correlated with the amounts of FAP-1
      mRNA, as determined by reverse transcriptase-polymerase chain reaction analysis.
      FAP-1 protein levels were investigated by immunoblotting in the National Cancer
      Institute's panel of 60 human tumor cell lines. Although FAP-1 failed to
      correlate with Fas-resistance across the entire tumor panel, Fas-resistance
      correlated significantly with FAP-1 expression (P: < or = 0.05) and a low Fas/FAP
      1 ratio (P: < or = 0.028) in ovarian cancer cell lines. FAP-1 expression was also
      evaluated in 95 archival ovarian cancer specimens using tissue-microarray
      technology. FAP-1 was expressed in nearly all tumors, regardless of histological
      type or grade, stage, patient age, response to chemotherapy, or patient survival.
      We conclude that FAP-1 correlates significantly with Fas resistance in ovarian
      cancer cell lines and is commonly expressed in ovarian cancers.

PMID- 11290553
TI  - Deletion of 11q23 and cyclin D1 overexpression are frequent aberrations in
      parathyroid adenomas.
AB  - Hyperparathyroidism may result from parathyroid hyperplasia or adenoma, or rarely
      from parathyroid carcinoma. Pericentromeric inversion of chromosome 11 that
      results in activation of the P:RAD1/cyclin D1 gene and tumor suppressor gene loss
      have been described as genetic abnormalities in the evolution of parathyroid
      neoplasms. We studied tissue samples taken from primary parathyroid hyperplasia,
      parathyroid adenoma, and histologically normal parathyroid tissue by comparative
      genomic hybridization, fluorescent in situ hybridization, and
      immunohistochemistry for cyclin D1. DNA copy number changes were infrequent in
      primary hyperplasia (4 of 24, 17%), but common in adenomas (10 of 16, 63%; P: =
      0.0059). The most common change was deletion of the entire chromosome 11 or a
      part of it, with a minimal common region at 11q23. This change was present in
      five (31%) adenomas and two (8%) primary hyperplasias. Fluorescent in situ
      hybridization confirmed the presence of both MEN1 alleles located at 11q13
      despite deletion of 11q23 in all three cases studied. Cyclin D1 was overexpressed
      in six (40%) of the 15 adenomas studied, whereas none of the 27 hyperplasias (P:
      = 0.0010) nor the five histologically normal tissue samples overexpressed cyclin
      D1. Either DNA copy number loss or cyclin D1 overexpression was present in 13
      (81%) of the 16 adenomas. We conclude that DNA copy number loss and cyclin D1
      overexpression are common in parathyroid adenomas. The region 11q23 is frequently
      lost in parathyroid adenomas and occasionally in parathyroid hyperplasias, and
      this suggests the possibility that a tumor suppressor gene that is important in
      their pathogenesis is present on 11q23.

PMID- 11290552
TI  - Inflammatory responses to amyloidosis in a transgenic mouse model of Alzheimer's
      disease.
AB  - Mutations in the amyloid precursor protein (APP) and presenilin-1 and -2 genes
      (PS-1, -2) cause Alzheimer's disease (AD). Mice carrying both mutant genes
      (PS/APP) develop AD-like deposits composed of beta-amyloid (Abeta) at an early
      age. In this study, we have examined how Abeta deposition is associated with
      immune responses. Both fibrillar and nonfibrillar Abeta (diffuse) deposits were
      visible in the frontal cortex by 3 months, and the amyloid load increased
      dramatically with age. The number of fibrillar Abeta deposits increased up to the
      oldest age studied (2.5 years old), whereas there were less marked changes in the
      number of diffuse deposits in mice over 1 year old. Activated microglia and
      astrocytes increased synchronously with amyloid burden and were, in general,
      closely associated with deposits. Cyclooxygenase-2, an inflammatory response
      molecule involved in the prostaglandin pathway, was up-regulated in astrocytes
      associated with some fibrillar deposits. Complement component 1q, an immune
      response component, strongly colocalized with fibrillar Abeta, but was also up
      regulated in some plaque-associated microglia. These results show: i) an
      increasing proportion of amyloid is composed of fibrillar Abeta in the aging
      PS/APP mouse brain; ii) microglia and astrocytes are activated by both fibrillar
      and diffuse Abeta; and iii) cyclooxygenase-2 and complement component 1q levels
      increase in response to the formation of fibrillar Abeta in PS/APP mice.

PMID- 11290554
TI  - Unique phenotypic profile of monocytoid B cells: differences in comparison with
      the phenotypic profile observed in marginal zone B cells and so-called monocytoid
      B cell lymphoma.
AB  - Monocytoid B cells (MBCs) are a subset of B cells that may be recognized in
      several reactive and tumoral lymph node conditions, including toxoplasmic
      lymphadenitis, infectious mononucleosis, and Hodgkin's lymphoma. Although this is
      a commonly observed cell population, which has even given its name to a type of
      lymphoma, MBC lymphoma, scarcely any information is available about the function
      and characteristics of this cell type. A relationship with marginal zone (MZ) B
      lymphocytes has been claimed for MBCs, but this has not yet been fully proven.
      Indeed, specific markers for MBCs are still lacking, which has made it difficult
      to analyze their relationship with other B cell subpopulations and confirm the
      existence of tumors deriving from this B cell subset. We used a panel of cell
      cycle markers to explore the characteristics of MBCs and their relationship with
      MZ B cells, nodal MZ lymphoma, and splenic MZ lymphoma. We therefore compared the
      phenotypic profile of MBCs in different conditions with normal MZ B cells within
      the spleen and mesenteric lymph nodes, with a group of seven cases of nodal
      MZ/MBC lymphoma and another group of five cases of splenic MZ lymphoma. MBCs were
      mainly in the G(0) to G(1) phases, as deduced from the presence of a proportion
      of between 10 and 35% Ki67-positive cells, whereas very low expression was
      observed with cyclin A and cyclin B staining. Nests of MBCs were clearly labeled
      by the expression of p21(WAF1), a cyclin-dependent kinase inhibitor (CKI), rarely
      detectable in benign lymphocytes, and by cyclin E. Basically all MBCs were bcl-2
      negative, and high cyclin D2 and cyclin D3 were also detected in these cells, at
      proportions and intensities above expected levels, when the percentage of
      proliferating cells was taken into account. p27(KIP1) expression was
      characterized by homogeneous reactivity, higher than that observed in other B
      cell populations with a relatively high-growth fraction. Immunoglobulin staining
      showed undetectable light and heavy chains. However, splenic MZ cells, nodal MZ
      lymphoma, and splenic MZ lymphoma showed a distinct expression of IgM and bcl-2,
      with high p27 (KIP1) nuclear expression and undetectable or low levels of cyclin
      A, B, E, or D, or p21(WAF1) expression. The data from this study show an
      unexpected immunophenotype in MBCs, different from the one observed in splenic
      and lymph node MZ B cells. This suggests that either MBCs are a unique B cell
      population from a distinct cell lineage, or if related to MZ cells, they would
      represent a definite differentiation stage characterized by a distinctive
      immunophenotype. They also show so-called MZ/MBC lymphoma to be more closely
      related to lymph node and splenic MZ B cells, as they do not share the most
      distinctive features of MBCs.

PMID- 11290555
TI  - Molecular clonality of in-transit melanoma metastasis.
AB  - In-transit melanoma is characterized by an aggressive pattern of recurrence that
      is associated with a poorer prognosis. Because in-transit melanoma is considered
      to result from the intralymphatic trapping of melanoma cells between the primary
      tumor and regional lymph nodes, it provides an excellent model to assess genetic
      events associated with early metastasis. The hypothesis of this study was to
      determine whether in-transit metastases are clonal in origin and therefore, may
      have specific genetic alterations uniquely associated with this disease and the
      development of early metastasis. This was assessed using loss of heterozygosity
      (LOH) analysis for specific DNA microsatellite loci. Seventy-nine paraffin
      embedded in-transit melanoma lesions from 25 patients (range, 2 to 9 lesions per
      patient; average, 3.4 lesions per patient) were assessed for LOH using eight
      microsatellite DNA markers on six chromosomes. In 19 of 25 patients (76%) LOH was
      demonstrated for at least one marker. The most frequent microsatellite marker
      demonstrating LOH was D9S157 (56%). Using LOH microsatellite markers to assess
      intertumor heterogeneity, six of 79 tumors (7.6%) demonstrated different profiles
      when compared to other lesions from the same patient. In-transit metastases from
      those patients demonstrating intertumor heterogeneity were further assessed using
      laser capture microdissection and DNA analysis, and revealed no significant
      intratumor heterogeneity. In conclusion, LOH was frequently observed in in
      transit melanoma metastasis. Based on LOH analysis, in-transit metastases are
      clonal in origin. The establishment of clinically successful in-transit melanoma
      metastasis requires specific genetic events that seem to be unique and
      homogeneous for each patient.

PMID- 11290556
TI  - Replicative senescence of biliary epithelial cells precedes bile duct loss in
      chronic liver allograft rejection: increased expression of p21(WAF1/Cip1) as a
      disease marker and the influence of immunosuppressive drugs.
AB  - Early chronic liver allograft rejection (CR) is characterized by distinctive
      cytological changes in biliary epithelial cells (BECs) that resemble cellular
      senescence, in vitro, and precede bile duct loss. If patients suffering from
      early CR are treated aggressively, the clinical and histopathological
      manifestations of CR can be completely reversed and bile duct loss can be
      prevented. We first tested whether the senescence-related p21(WAF1/Cip1) protein
      is increased in BECs during early CR, and whether treatment reversed the
      expression. The percentage of p21+ BECs and the number of p21+ BECs per portal
      tract is significantly increased in early CR (26 +/- 17% and 3.6 +/- 3.1)
      compared to BECs in normal liver allograft biopsies or those with nonspecific
      changes (1 +/- 1% and 0.1 +/- 0.3; P: < 0.0001 and P: < 0.02), chronic hepatitis
      C (2 +/- 3% and 0.7 +/- 1; P: < 0.0001 and P: < 0.04) or obstructive
      cholangiopathy (7 +/- 7% and 0.7 +/- 0.6; P: < 0.006 and P: = 0.04). Successful
      treatment of early CR is associated with a decrease in the percentage of p21+
      BECs and the number of p21+ BECs per portal tract. In vitro, nuclear
      p21(WAF1/Cip1) expression is increased in large and multinucleated BECs, and is
      induced by transforming growth factor (TGF)-beta. TGF-beta1 also increases
      expression of TGF-beta receptor II, causes phosphorylation of SMAD-2 and nuclear
      translocation of p21(WAF1/Cip1), which inhibits BEC growth. Because conversion
      from cyclosporine to tacrolimus is an effective treatment for early CR, we next
      tested whether these two immunosuppressive drugs directly influenced BEC growth
      in vitro. The results show that cyclosporine, but not tacrolimus, stimulates BEC
      TGF-beta1 production, which in turn, causes BEC mito-inhibition and up-regulation
      of nuclear p21(WAF1/Cip1). In conclusion, expression of the senescence-related
      p21(WAF1/Cip1) protein is increased in BECs during early CR and decreases with
      successful recovery. Replicative senescence accounts for the characteristic BEC
      cytological alterations used for the diagnosis of early CR and lack of a
      proliferative response to injury. The ability of cyclosporine to inhibit the
      growth of damaged BECs likely accounts for the relative duct sparing properties
      of tacrolimus.

PMID- 11290557
TI  - Elevated proportion of natural killer T cells in periodontitis lesions: a common
      feature of chronic inflammatory diseases.
AB  - Although periodontitis is a chronic inflammatory disease caused by a group of so
      called periodontopathic bacteria, autoimmune mechanisms have also been implicated
      in the disease process. Recently, a unique subset of lymphocytes designated
      natural killer (NK) T cells expressing the Valpha24JalphaQ invariant T cell
      receptor (TCR) has been reported to have a regulatory role in certain autoimmune
      diseases. Therefore, we investigated the proportion of the invariant
      Valpha24JalphaQ TCR within the Valpha24 T cell population in periodontitis
      lesions and gingivitis lesions using single-strand conformation polymorphism
      methodology. NK T cells were identified with a specific JalphaQ probe whereas the
      total Valpha24 TCR was identified using an internal Calpha probe. NK T cells were
      a significant proportion of the total Valpha24 population both in periodontitis
      lesions and to a lesser extent in gingivitis lesions but not in the peripheral
      blood of either periodontitis patients or nondiseased controls. Using
      immunohistochemistry, some of Valpha24(+) cells in the periodontitis lesions
      seemed to associate with CD1d(+) cells, which are specific antigen-presenting
      cells for NK T cells. Although the mechanism underlying the elevation of NK T
      cells in periodontitis and in gingivitis lesions remains unclear, it can be
      postulated that NK T cells are recruited to a play regulatory role in the immune
      response to bacterial infection.

PMID- 11290558
TI  - Vascular repair after menstruation involves regulation of vascular endothelial
      growth factor-receptor phosphorylation by sFLT-1.
AB  - Regeneration of the endometrium after menstruation requires a rapid and highly
      organized vascular response. Potential regulators of this process include members
      of the vascular endothelial growth factor (VEGF) family of proteins and their
      receptors. Although VEGF expression has been detected in the endometrium, the
      relationship between VEGF production, receptor activation, and endothelial cell
      proliferation during the endometrial cycle is poorly understood. To better
      ascertain the relevance of VEGF family members during postmenstrual repair, we
      have evaluated ligands, receptors, and activity by receptor phosphorylation in
      human endometrium throughout the menstrual cycle. We found that VEGF is
      significantly increased at the onset of menstruation, a result of the additive
      effects of hypoxia, transforming growth factor-alpha, and interleukin-1beta. Both
      VEGF receptors, FLT-1 and KDR, followed a similar pattern. However, functional
      activity of KDR, as determined by phosphorylation studies, revealed activation in
      the late menstrual and early proliferative phases. The degree of KDR
      phosphorylation was inversely correlated with the presence of sFLT-1. Endothelial
      cell proliferation analysis in endometrium showed a peak during the late
      menstrual and early proliferative phases in concert with the presence of VEGF,
      VEGF receptor phosphorylation, and decrease of sFLT-1. Together, these results
      suggest that VEGF receptor activation and the subsequent modulation of sFLT-1 in
      the late menstrual phase likely contributes to the onset of angiogenesis and
      endothelial repair in the human endometrium.

PMID- 11290559
TI  - Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response
      to transforming growth factor-beta in human fibrotic lung fibroblasts and
      promotes bleomycin-induced pulmonary fibrosis in mice.
AB  - Prostaglandin E(2) (PGE(2)) inhibits fibroblast proliferation and collagen
      production. Its synthesis by fibroblasts is induced by profibrotic mediators
      including transforming growth factor (TGF)-beta(1). However, in patients with
      pulmonary fibrosis, PGE(2) levels are decreased. In this study we examined the
      effect of TGF-beta(1) on PGE(2) synthesis, proliferation, collagen production,
      and cyclooxygenase (COX) mRNA levels in fibroblasts derived from fibrotic and
      nonfibrotic human lung. In addition, we examined the effect of bleomycin-induced
      pulmonary fibrosis in COX-2-deficient mice. We demonstrate that basal and TGF
      beta(1)-induced PGE(2) synthesis is limited in fibroblasts from fibrotic lung.
      Functionally, this correlates with a loss of the anti-proliferative response to
      TGF-beta(1). This failure to induce PGE(2) synthesis is because of an inability
      to up-regulate COX-2 mRNA levels in these fibroblasts. Furthermore, mice
      deficient in COX-2 exhibit an enhanced response to bleomycin. We conclude that a
      decreased capacity to up-regulate COX-2 expression and COX-2-derived PGE(2)
      synthesis in the presence of increasing levels of profibrotic mediators such as
      TGF-beta(1) may lead to unopposed fibroblast proliferation and collagen synthesis
      and contribute to the pathogenesis of pulmonary fibrosis.

PMID- 11290561
TI  - Modulation of chemokine production and inflammatory responses in interferon-gamma
      and tumor necrosis factor-R1-deficient mice during Trypanosoma cruzi infection.
AB  - Infection with Trypanosoma cruzi causes a strong inflammatory reaction at the
      inoculation site and, later, in the myocardium. The present study investigates
      the role of cytokines as modulators of T. cruzi-induced chemokine expression in
      vivo and in vitro. In macrophage cultures, although the stimulation with
      interferon (IFN)-gamma increases the expression of IP-10, it blocks KC
      expression. Tumor necrosis factor (TNF)-alpha, on the other hand, potentiates KC,
      IP-10, macrophage inflammatory protein-1alpha, and JE/monocyte chemotatic protein
      1 expression. Interleukin-10 and transforming growth factor-beta inhibited almost
      all chemokines tested. The role of IFN-gamma and TNF-alpha in chemokine
      modulation during infection was investigated in T. cruzi-infected IFN-gamma
      deficient (GKO) or TNF-R1/p55-deficient (p55-/-) mice. The expression of
      chemokines detected in the inoculation site correlated with the infiltrating cell
      type observed. Although GKO mice had a delayed and intense neutrophilic
      infiltrate correlating with the expression of KC and macrophage inflammatory
      protein-2, none of the above was observed in p55-/- mice. The detection of
      infiltrating T cells, Mig, and IP-10 in the myocardium was observed in wild-type
      and p55-/-, but not in GKO mice. Together, these results suggest that the
      regulatory roles of IFN-gamma and TNF-alpha on chemokine expression may play a
      crucial role in the modulation of the inflammatory response during T. cruzi
      infection and mediate resistance to infection.

PMID- 11290560
TI  - Gas6 regulates mesangial cell proliferation through Axl in experimental
      glomerulonephritis.
AB  - Proliferation of mesangial cells is a hallmark of glomerular disease, and
      understanding its regulatory mechanism is clinically important. Previously, we
      demonstrated that the product of growth arrest-specific gene 6 (Gas6) stimulates
      mesangial cell proliferation through binding to its cell-surface receptor Axl in
      vitro. We also showed that warfarin and the extracellular domain of Axl
      conjugated with Fc portion of human IgG1 (Axl-Fc) inhibit mesangial cell
      proliferation by interfering the Gas6/Axl pathway in vitro. In the present study,
      therefore, we examined in vivo roles of Gas6 and Axl in an experimental model of
      mesangial proliferative glomerulonephritis induced by the injection of anti
      Thy1.1 antibody (Thy1 GN). In Thy1 GN, expression of Gas6 and Axl was markedly
      increased in glomeruli, and paralleled the progression of mesangial cell
      proliferation. Administration of warfarin or daily injection of Axl-Fc inhibited
      mesangial cell proliferation, and abolished the induction of platelet-derived
      growth factor-B mRNA and protein in Thy1 GN. Moreover, the anti-proliferative
      effect of warfarin was achieved at lower concentrations than those in routine
      clinical use. These findings indicate that the Gas6/Axl pathway plays a key role
      in mesangial cell proliferation in vivo, and could be a potentially important
      therapeutic target for the treatment of renal disease.

PMID- 11290562
TI  - Synthesis of C-X-C and C-C chemokines by human peritoneal fibroblasts: induction
      by macrophage-derived cytokines.
AB  - Leukocyte accumulation during peritonitis is believed to be controlled by
      chemotactic factors released by resident peritoneal macrophages or mesothelial
      cells. Recent data indicate, however, that in many tissues fibroblasts play a key
      role in mediating leukocyte recruitment. We have therefore examined human
      peritoneal fibroblasts (HPFBs) for the expression and regulation of C-X-C and C-C
      chemokines. Quiescent HPFBs secreted monocyte chemoattractant protein (MCP)-1 and
      interleukin (IL)-8 constitutively. This release could be dose-dependently
      augmented with the pro-inflammatory cytokines IL-1beta and tumor necrosis factor
      alpha. Stimulated IL-8 production reached a plateau within 48 hours while MCP-1
      continued to accumulate throughout 96 hours. Induction of IL-8 and MCP-1
      synthesis by HPFBs was also triggered by peritoneal macrophage-conditioned
      medium. This effect was partly related to the presence of IL-1beta as
      demonstrated by IL-1 receptor antagonist inhibition. Pretreatment of HPFBs with
      actinomycin D or puromycin dose-dependently reduced cytokine-stimulated IL-8 and
      MCP-1 secretion, which suggested de novo chemokine synthesis. Indeed, exposure of
      HPFBs to IL-1beta and tumor necrosis factor-alpha produced a significant up
      regulation of IL-8 and MCP-1 mRNA. This effect was associated with the rapid
      induction of nuclear factor-kappaB binding activity mediated through p65 and p50
      subunits, and with a transient increase in the mRNA expression for RelB and
      inhibitory protein kappaB-alpha proteins. These data indicate that peritoneal
      fibroblasts are capable of generating large quantities of chemokines under a
      tight control of nuclear factor-kappaB/Rel transcription factors. Thus,
      peritoneal fibroblast-derived chemokines may contribute to the intraperitoneal
      recruitment of leukocytes during peritonitis.

PMID- 11290564
TI  - Cartilage-specific matrix protein chondromodulin-I is associated with chondroid
      formation in salivary pleomorphic adenomas: immunohistochemical analysis.
AB  - Chondromodulin-I (ChM-I) is a novel cartilage-specific matrix protein. In the
      growth plates of the long bones, ChM-I was shown to be expressed in mature to
      upper hypertrophic chondrocytes, and to be deposited in the cartilage matrix. As
      ChM-I strongly inhibits angiogenesis, cartilage is avascular. Also, ChM-I has
      bifunctional activity against chondrocyte proliferation. On the other hand,
      pleomorphic adenomas of the salivary glands frequently have chondroid elements.
      To elucidate the relationship between chondroid formation and hypovascularity in
      salivary pleomorphic adenomas, we immunohistochemically examined the expression
      and localization of ChM-I in 35 cases of this tumor. ChM-I was immunolocalized to
      the lacunae in the chondroid elements of pleomorphic adenomas (100%). Type II
      collagen and aggrecan were immunolocalized throughout the matrix around lacuna
      cells of the chondroid element (100%, 91.7%), and ChM-I was infrequently
      immunolocalized to the spindle-shaped myoepithelial cells in the myxoid element
      (37.5%). Fibroblast growth factor-2 was strongly immunolocalized to the lacuna
      cells in the chondroid element (100%), among the neoplastic myoepithelial cells
      in the myxoid elements (96.9%), and on the basement membranes around the solid
      nests of neoplastic myoepithelial cells (71.4%). Although CD34 is a marker of
      endothelial cells, CD34 was expressed in the endothelial cells in only a few
      areas around the epithelial elements and in the fibrous element of pleomorphic
      adenomas. No signals for CD34 were observed in chondroid elements in pleomorphic
      adenomas (P < 0.001), but a few signals were seen in the myxoid elements (P <
      0.05). These findings suggested that lacuna cells and neoplastic myoepithelial
      cells expressed ChM-I, and that this molecule may play an important role in
      hypovascularity and chondroid differentiation in pleomorphic adenoma. In
      conclusion, pleomorphic adenoma expressed ChM-I, which is involved in
      hypovascularity and chondroid formation in this type of tumor.

PMID- 11290563
TI  - c-MET expression in myofibroblasts: role in autocrine activation and prognostic
      significance in lung adenocarcinoma.
AB  - Hepatocyte growth factor (HGF) plays important roles in tumor development and
      progression. It is currently thought that the main action of HGF is of a
      paracrine nature: HGF produced by mesenchymal cells acts on epithelial cells that
      express its receptor c-MET. In this investigation, we explored the significance
      of c-MET expression in myofibroblasts, both in culture and in patients with lung
      adenocarcinoma. We first showed that human myofibroblasts derived from primary
      lung cancer expressed c-MET mRNA and protein by reverse transcription-polymerase
      chain reaction and Western blot analysis. Proliferation of myofibroblasts was
      stimulated in a dose-dependent manner by exogenously added recombinant human HGF
      whereas it was inhibited in a dose-dependent manner by neutralizing antibody to
      HGF. The addition of HGF in the culture medium stimulated tyrosine
      phosphorylation of c-MET. The c-MET protein was immunohistochemically detected in
      myofibroblasts in the invasive area of lung adenocarcinoma. Finally, the
      prognostic significance of c-MET expression in stromal myofibroblasts was
      explored in patients with small-sized lung adenocarcinomas. c-MET-positive
      myofibroblasts were observed in 69 of 131 cases (53%). A significant relationship
      between myofibroblast c-MET expression and shortened patient survival was
      observed in a whole cohort of patients including all pathological stages (two
      sided P: = 0.0089 by log-rank test) and in patients with stage IA disease (two
      sided P: = 0.0019 by log-rank test). These data suggest that the HGF/c-MET system
      constitutes an autocrine activation loop in cancer-stromal myofibroblasts. This
      autocrine system may play a role in invasion and metastasis of lung
      adenocarcinoma.

PMID- 11290565
TI  - Expression of leukemia-associated antigen, JL1, in bone marrow and thymus.
AB  - The identification of immunophenotypic markers with restricted expression has
      long been a critical issue in diagnostic and therapeutic advances for acute
      leukemias. We previously developed a monoclonal antibody against a new thymocyte
      surface antigen, JL1, and showed that JL1 is expressed in the majority of acute
      leukemia cases. In this study, using multiparameter flow cytometric analyses, we
      found that JL1 was uniquely expressed in subpopulations of normal bone marrow
      (BM) cells, implying the association of JL1 with the differentiation and
      maturation process. Although CD34(+) CD10(+) lymphoid precursors and some of
      maturing myeloid cells express JL1, neither CD34(+) CD38(-/lo) nor CD34(+)
      AC133(+) noncommitted pluripotent stem cells do. As for the myeloid precursors,
      CD34(+) CD33(+) cells do not express JL1. During lymphopoiesis, JL1 on the
      earliest lymphoid precursors disappear in the CD20(+) sIgM(+) stage of B-cell
      development or after CD1a down-regulation in thymocytes. Despite the highly
      restricted expression of JL1 in normal BM cells, most of the leukemias express
      JL1 irrespective of their immunophenotypes. These results indicate that JL1 is
      not only a novel differentiation antigen of hematopoietic cells, but also a
      leukemia-associated antigen. Therefore, we suggest that JL1 be a candidate
      molecule in acute leukemia for the diagnosis and immunotherapy that spares the
      normal BM stem cells.

PMID- 11290566
TI  - Structural analysis of Pick's disease-derived and in vitro-assembled tau
      filaments.
AB  - Pick's and Alzheimer's diseases are distinct neurodegenerative disorders both
      characterized in part by the presence of intracellular filamentous tau protein
      inclusions. The tight bundles of paired helical filaments (PHFs) of tau protein
      found in Alzheimer's disease (AD) differ from the tau filaments of Pick's disease
      in their morphology, distribution, and pathological structure as identified by
      silver impregnation. The filaments of Pick's disease are loosely arranged in
      pathognomonic spherical inclusions found in ballooned neurons, whereas the tau
      pathology of AD is classically described as a triad of neuropil threads,
      neurofibrillary tangles, and dystrophic neurites surrounding and invading
      plaques. In this study we used the high-resolution technique of scanning
      transmission electron microscopy to characterize and compare the filaments found
      in Pick's disease with those found in AD. In addition, we determined the mass/nm
      length and density of arachidonic acid-induced in vitro-assembled filaments.
      Three morphologically distinct populations of Pick's filaments were identified
      but each was indistinguishable from AD-PHFs in mass/nm length and density.
      Filaments assembled in vitro from single isoforms were similar in mass/nm length,
      but less dense than AD-PHFs and Pick's disease filaments. Finally, we provide
      clear structural evidence that a PHF, whether found in disease or assembled in
      vitro, is composed of two distinct intertwined filaments.

PMID- 11290567
TI  - Development of a novel proteomic approach for the detection of transitional cell
      carcinoma of the bladder in urine.
AB  - Development of noninvasive methods for the diagnosis of transitional cell
      carcinoma (TCC) of the bladder remains a challenge. A ProteinChip technology
      (surface enhanced laser desorption/ionization time of flight mass spectrometry)
      has recently been developed to facilitate protein profiling of biological
      mixtures. This report describes an exploratory study of this technology as a TCC
      diagnostic tool. Ninety-four urine samples from patients with TCC, patients with
      other urogenital diseases, and healthy donors were analyzed. Multiple protein
      changes were reproducibly detected in the TCC group, including five potential
      novel TCC biomarkers and seven protein clusters (mass range, 3.3 to 133 kd). One
      of the TCC biomarkers (3.4 kd) was also detected in bladder cancer cells procured
      from bladder barbotage and was identified as defensin. The TCC detection rates
      provided by the individual markers ranged from 43 to 70% and specificities from
      70 to 86%. Combination of the protein biomarkers and clusters, increased
      significantly the sensitivity for detecting TCC to 87% with a specificity of 66%.
      Interestingly, this combinatorial approach provided sensitivity of 78% for
      detecting low-grade TCC compared to only 33% of voided urine or bladder-washing
      cytology. Collectively these results support the potential of this proteomic
      approach for the development of a highly sensitive urinary TCC diagnostic test.

PMID- 11290569
TI  - Inverse relationship between microsatellite instability and K-ras and p53 gene
      alterations in colon cancer.
AB  - Some studies have shown an inverse relationship between microsatellite
      instability in colon cancer and mutations in p53 and K-ras, whereas others have
      not. We therefore evaluated these features in a population-based sample of 496
      individuals with colon cancer. Microsatellite instability was determined by a
      panel of 10 tetranucleotide repeats, the Bethesda consensus panel of mono- and
      dinucleotide repeats, and coding mononucleotide repeats in transforming growth
      factor-beta receptor type II, hMSH3, BAX, hMSH6, and insulin-like growth factor
      receptor type II. Mutations in codons 12 and 13 in K-ras were evaluated by
      sequencing. p53 overexpression (as detected by immunohistochemistry) was used as
      an indicator of p53 mutation; this was evaluated in 275 of the tumors. K-ras
      mutations were present in 33.2% of tumors, p53 overexpression in 51.5%, and
      microsatellite instability (as determined by the Bethesda consensus panel) in
      12.5%. K-ras mutations were significantly less common in unstable tumors than
      stable tumors (11.8% versus 36.9%, P: < 0.001). p53 overexpression was
      significantly less common in unstable tumors than stable tumors (20.0% versus
      55.7%, P: < 0.001). These inverse relationships between microsatellite
      instability and ras gene mutations and p53 overexpression were shown to be
      independent of tumor site in logistic regression analyses. All other measures of
      instability also showed statistically significant inverse relationships
      independent of tumor site with alterations in ras and p53, and instability
      results determined by the panel of 10 tetranucleotide repeats were highly
      significantly related to those determined by the Bethesda consensus panel. Coding
      mononucleotide repeat mutations were significantly more common in unstable tumors
      than stable tumors (85.7% versus 1.0%, P: < 0.001). We conclude that there is an
      inverse relationship between microsatellite instability and mutations in p53 and
      K-ras, and that the molecular profile of colon cancers with microsatellite
      instability is characterized by relatively infrequent mutations in K-ras and p53
      and relatively frequent mutations in coding mononucleotide repeats.

PMID- 11290568
TI  - Chemokine expression dynamics in mycobacterial (type-1) and schistosomal (type-2)
      antigen-elicited pulmonary granuloma formation.
AB  - Transcript expression of 24 chemokines (CKs) was examined throughout 8 days in
      mouse lungs with type-1 (Th1) or type-2 (Th2) cytokine-mediated granulomas
      induced by bead-immobilized mycobacterial purified protein derivative or
      Schistosoma mansoni egg antigens. Where possible, CK protein levels were also
      measured. In addition, we examined effects of in vivo cytokine depletions.
      Findings were as follows: 1) bead challenge induced increases in 18 of 24 CK
      transcripts with type-1 and type-2 responses displaying different patterns. CKs
      fell into four categories: a) type-1-dominant (gamma-interferon-inducible protein
      (IP-10), monokine induced by INF-gamma (MIG), macrophage inflammatory protein-2
      (MIP-2), lipopolysaccharide-induced chemokine (LIX), rodent growth-related
      oncogene homologue (KP), macrophage inflammatory protein-1alpha (MIP-1alpha) and 
      1beta (MIP-1beta), lymphotactin), b) type-2-dominant (eotaxin, monocyte
      chemotactic protein-2 (MCP-2) and -3 (MCP-3), liver and activation-regulated
      chemokine (LARC), T cell activation protein-3 (TCA-3), c) type-1 and type-2 co
      dominant (MCP-1, MCP-5, monocyte-derived chemokine (MDC), thymus and activation
      related chemokine (TARC), C10), and d) constitutive (lungkine, secondary lymphoid
      tissue chemokine (SLC), EBI1-ligand chemokine (ELC), fractalkine, macrophage
      inflammatory protein-1gamma (MIP1-gamma), and stromal cell derived factor-1alpha
      (SDF1-alpha). 2) CKs displayed characteristic temporal patterns. CXC (IP-10, MIG,
      MIP-2, LIX, KC) and certain CC (MCP-1, MCP-5, MIP-1alpha, MIP-1beta) CKs were
      produced maximally within 1 to 2 days. Others (MCP-2, MCP-3, eotaxin,
      lymphotactin, LARC, TCA-3) displayed peak expression later. 3) Interferon-gamma
      neutralization profoundly abrogated MIG, but had little effect on other CKs.
      Tumor necrosis factor-alpha neutralization caused up to 50% reduction in a range
      of CKs. These findings indicate that type-1 and type-2 granulomas display
      characteristic CK profiles with coordinated expression that is under cytokine
      mediated regulation.

PMID- 11290572
TI  - Virchow and apoptosis.

PMID- 11290571
TI  - An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus
      papio frequently induces fatal lymphoproliferative disorders with hemophagocytic
      syndrome in rabbits.
AB  - Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often
      associated with fatal infectious mononucleosis. However, the animal model for EBV
      AHS has not been developed. We reported the first animal model for EBV-AHS using
      rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%)
      rabbits inoculated intravenously with HVP-producing cells developed fatal
      lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation.
      LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11
      rabbits. The peroral spray of cell-free HVP induced the virus infection with
      increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and
      two of these three infected rabbits died of LPD with HPS. Autopsy revealed
      hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing
      EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently
      involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was
      observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was
      detected in the tissues and peripheral blood from the infected rabbits by
      polymerase chain reaction or Southern blot analysis. Reverse transcriptase
      polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts,
      suggesting latency type III infection. These data indicate that the high rate of
      rabbit LPD with HPS induction is caused by HVP. This system is useful for
      studying the pathogenesis, prevention, and treatment of human EBV-AHS.

PMID- 11290570
TI  - Pediatric high-grade astrocytomas show chromosomal imbalances distinct from adult
      cases.
AB  - We studied 23 pediatric high-grade astrocytomas by comparative genomic
      hybridization. Chromosomal imbalances were found in 10 of 10 anaplastic
      astrocytomas and 11 of 13 glioblastomas and consisted of +1q (43%), +3q (26%),
      +1p, +2q, +5q (22%), -22q (34%), -6q, -10q (30%), -9q, -11q, -13q, -16q, and -17p
      (22%). Anaplastic astrocytomas frequently showed +5q (40%), +1q (30%), -22q
      (50%), -6q, -9q (40%), and -12q (30%); glioblastomas +1q (54%), +3q (38%), +2q,
      +17q (23%), -6q, -8q, -10q, -13q, and -17p (31%). Minimal common regions mapped
      to +1q21-41, +3q27-qter, +2q31-32, +5q14-22, -22q12-qter, -10q23-25, -6q25-qter, 
      9q34.2, -11q14-22, -16q22-qter, and -17p. High-level gains were located on 1q (7
      cases), 2q, 7q (4 cases), 3q (3 cases), 9, 17q (2 cases), 4q, 8q, 18, and 20q (1
      case). A significantly shorter survival was found for anaplastic astrocytomas
      showing +1q (P: < 0.05), MIB-1 proliferation index >25% (P: < 0.001) and
      glioblastomas (P: < 0.05). Compared with adult cases, +1p, +2q, and +21q as well
      as -6q, -11q, and -16q were more frequent in pediatric malignant astrocytomas.
      Among the latter +5q, -6q, -9q, -12q, and -22q were characteristic for pediatric
      anaplastic astrocytomas and +1q, +3q, +16p, -8q, and -17p for pediatric
      glioblastomas. Our results show that chromosomal aberrations differ between
      pediatric anaplastic astrocytomas and glioblastomas as well as between pediatric
      and adult high-grade astrocytomas, supporting the notion of a different genetic
      pathway. Furthermore, gains of chromosomal material on 1q might be correlated
      with a worse prognosis in pediatric anaplastic astrocytomas.

PMID- 11290574
TI  - If it's Tuesday, this must be a Belgian chemokine.

PMID- 11290575
TI  - Point mutations in the FLT3 gene in AML.

PMID- 11290576
TI  - A time to live, a time to die.

PMID- 11290577
TI  - G-CSF: early benefits but late risks?

PMID- 11290578
TI  - Access to the biomedical literature: a stand against coercion.

PMID- 11290579
TI  - Identification of a blood-derived chemoattractant for neutrophils and lymphocytes
      as a novel CC chemokine, Regakine-1.
AB  - Chemokines constitute a large family of chemotactic cytokines that selectively
      attract different blood cell types. Although most inflammatory chemoattractants
      are only induced and released in the circulation during acute infection, a
      restricted number of CXC and CC chemokines are constitutively present in normal
      plasma at high concentrations. Here, such a chemotactic protein was purified to
      homogeneity from serum and fully identified as a novel CC chemokine by mass
      spectrometry and amino acid sequence analysis. The protein, tentatively
      designated Regakine-1, shows less than 50% sequence identity with any known
      chemokine. This novel CC chemokine chemoattracts both neutrophils and lymphocytes
      but not monocytes or eosinophils. Its modest chemotactic potency but high blood
      concentration is similar to that of other chemokines present in the circulation,
      such as hemofiltrate CC chemokine-1, platelet factor-4, and beta-thromboglobulin.
      Regakine-1 did not induce neutrophil chemokinesis. However, it synergized with
      the CXC chemokines interleukin-8 and granulocyte chemotactic protein-2, and the
      CC chemokine monocyte chemotactic protein-3, resulting in an at least a 2-fold
      increase of the neutrophil and lymphocyte chemotactic response, respectively. The
      biologic effects of homogeneous natural Regakine-1 were confirmed with chemically
      synthesized chemokine. Like other plasma chemokines, it is expected that Regakine
      1 plays a unique role in the circulation during normal or pathologic conditions.

PMID- 11290580
TI  - The C-class chemokine lymphotactin costimulates the apoptosis of human CD4(+) T
      cells.
AB  - Clonal expansion of activated T cells is controlled by homeostatic mechanisms
      leading to cell death of a large proportion of the cells. The CD3/TcR pathway
      induces cell death, mostly when triggered in the absence of costimulatory signal.
      The unique T cell-specific chemokine of the C class, lymphotactin (Lptn), has
      recently been shown to inhibit the production of Th1-type lymphokines in human
      CD4(+) T cells. The present study shows the ability of Lptn to costimulate the
      death of CD4(+) T lymphocytes triggered through CD3/TCR. The Lptn-mediated
      increased cell death exhibited characteristic features of apoptosis, as mainly
      determined by DNA fragmentation and exposure of an apoptotic-specific
      mitochondrial antigen. This apoptosis was dependent on Fas/FasL signaling, was
      not rescued by addition of interleukin 2, and proceeded with a predominant
      processing of both initiator procaspase-9 and effector procaspase-7. These
      caspase activities were further evidenced by specific cleavage of poly(ADP
      ribose) polymerase (PARP) and CD3/TCR zeta-chain, but not DNA fragmentation
      factor (DFF45). This study demonstrates that the functional repertoire of Lptn in
      the regulation of human CD4(+) T-lymphocyte activation includes the ability to
      costimulate apoptosis.

PMID- 11290581
TI  - betaMinor-globin messenger RNA accumulation in reticulocytes governs improved
      erythropoiesis in beta thalassemic mice after erythropoietin complementary DNA
      electrotransfer in muscles.
AB  - Mechanisms governing the induction of effective erythropoiesis in response to
      erythropoietin (Epo) oversecretion have been investigated in beta thalassemic
      C57Bl/6(Hbbth) mice. Naked DNA encoding an expression vector for mouse Epo was
      introduced into skeletal muscles by electrotransfer. A transient increase of
      serum Epo concentrations with a proportional augmentation of hematocrit values
      was observed. Various parameters relevant to beta thalassemia were surveyed in
      blood samples taken before treatment, at the peak of Epo secretion, and when the
      phenotype reverted to anemia. We measured globin messenger RNA (mRNA) levels in
      reticulocytes by real-time quantitative polymerase chain reaction, globin chain
      synthesis levels, and several indicators of erythrocyte membrane quality,
      including bound alpha chains, bound immunoglobulins, main protein components, and
      iron compartmentalization. Data indicated that high serum Epo levels primarily
      affect betaminor-globin mRNA accumulation in reticulocytes. Other changes
      subsequent to intense Epo stimulation, like increased betaminor/alpha-globin
      chain synthesis ratio, reduced levels of alpha chains and immunoglobulins bound
      to membranes, improved spectrin/band 3 ratio, increased red blood cell survival,
      and improved erythropoiesis appeared as consequences of increased betaminor
      globin mRNA levels. This conclusion is consistent with models postulating that
      intense Epo stimulation induces the expansion and differentiation of erythroid
      progenitors committed to fetal erythropoiesis. Although phenotypic correction was
      partial in mice, and comparable achievements will probably be more difficult to
      obtain in humans, naked DNA electrotransfer may provide a safe and low-cost
      method for reassessing the potentials of Epo as an inducer of fetal
      erythropoiesis reactivation in patients with beta thalassemia.

PMID- 11290582
TI  - Systemic circulation of poly(L-lysine)/DNA vectors is influenced by polycation
      molecular weight and type of DNA: differential circulation in mice and rats and
      the implications for human gene therapy.
AB  - Effective gene therapy for diseases of the circulation requires vectors capable
      of systemic delivery. The molecular weight of poly(L-lysine) (pLL) has a
      significant effect on the circulation of pLL/DNA complexes in mice, with
      pLL(211)/DNA complexes displaying up to 20 times greater levels in the blood
      after 30 minutes compared with pLL(20)/DNA. It is shown that pLL(20)/DNA
      complexes fix mouse complement C3 in vitro, independent of immunoglobulin
      binding; are less soluble in the blood in vivo; bind erythrocytes; are rapidly
      removed by the liver, where they associate predominantly with Kupffer cells; and
      result in a rapid increase in hepatic leukocytes expressing high levels of
      complement receptor 3 (CR3). The circulation properties of these complexes are
      also dependent on the type of DNA used, with circular plasmid DNA complexes
      exhibiting increased circulation compared with linear DNA. PLL(211)/DNA complexes
      bind erythrocytes and associate with Kupffer cells but, in contrast, do not fix
      mouse complement in vitro and are unaffected by the type of DNA used. In rats,
      both types of complexes produce hematuria and are rapidly removed from the
      circulation. Correlation of in vivo and in vitro results suggests that the
      solubility of complexes in physiological saline and species-matched complement
      fixation and erythrocyte lysis may correlate with systemic circulation. Analysis
      using human blood in vitro shows no hemolysis, but both types of complexes fix
      complement and bind IgG, suggesting that pLL/DNA complexes may be rapidly cleared
      from the human circulation.

PMID- 11290584
TI  - Asymmetrical segregation of chromosomes with a normal metaphase/anaphase
      checkpoint in polyploid megakaryocytes.
AB  - During differentiation, megakaryocytes increase ploidy through a process called
      endomitosis, whose mechanisms remain unknown. As it corresponds to abortive
      mitosis at anaphase and is associated with a multipolar spindle, investigation of
      chromosome segregation may help to better understand this cell-cycle abnormality.
      To examine this variation, a new method was developed to combine primed in situ
      labeling to label centromeres of one chromosome category and immunostaining of
      tubulin. Human megakaryocytes were obtained from normal bone marrow culture. By
      confocal microscopy, this study demonstrates an asymmetrical distribution of
      chromosomes (1 or 7) either between the spindle poles at anaphase stage of
      endomitosis and between the different lobes of interphase megakaryocyte nuclei.
      The metaphase/anaphase checkpoint appears normal on the evidence that under
      nocodazole treatment megakaryocytes progressively accumulate in pseudo-metaphase,
      without spontaneous escape from this blockage. Immunostaining of p55CDC/hCDC20
      with similar kinetochore localization and dynamics as during normal mitosis
      confirms this result. HCdh1 was also expressed in megakaryocytes, and its main
      target, cyclin B1, was normally degraded at anaphase, suggesting that the hCdh1
      anaphase-promoting complex checkpoint was also functional. This study found the
      explanation for these unexpected results of an asymmetrical segregation coupled
      to normal checkpoints by careful analysis of multipolar endomitotic spindles:
      whereas each aster is connected to more than one other aster, one chromosome may
      segregate symmetrically between 2 spindle poles and still show asymmetrical
      segregation when the entire complex spindle is considered.

PMID- 11290583
TI  - A common epitope is shared by activated signal transducer and activator of
      transcription-5 (STAT5) and the phosphorylated erythropoietin receptor:
      implications for the docking model of STAT activation.
AB  - Erythropoietin (EPO) specifically activates the Janus kinase JAK2 and the
      transcription factor signal transducer and activator of transcription-5 (STAT5).
      All members of the STAT family are tyrosine phosphorylated in response to
      cytokine stimulation at a conserved carboxy-terminal tyrosine, Y694, in the case
      of STAT5. To determine structural features important for STAT signaling, we
      generated an activation-specific STAT5 antibody using a phosphopeptide containing
      amino acids 687 to 698 of STAT5 as antigen. This antibody specifically recognizes
      tyrosine- phosphorylated STAT5 but not nonphosphorylated STAT5. In
      immunoprecipitation reactions from cell lines and primary erythroblasts, 2
      distinct polyclonal activation-specific STAT5 antibodies selectively
      immunoprecipitate the tyrosine phosphorylated EPO receptor (EPO-R) in addition to
      STAT5 under native and denaturing conditions. We propose that the activation
      specific STAT5 antibody recognizes the 2 substrates to which the STAT5 SH2 domain
      interacts, namely, the tyrosine- phosphorylated EPO-R and STAT5 itself. Several
      studies have implicated EPO-R Y343, Y401, Y431, and Y479 in the recruitment of
      STAT5. Using a series of EPO-R tyrosine mutants expressed in Ba/F3 cells, we have
      shown that the activation-specific STAT5 antibody immunoprecipitates an EPO-R
      containing only 2 tyrosines at positions 343 and 401, confirming the importance
      of these tyrosines in STAT5 recruitment. These data uncover a novel aspect of
      STAT SH2 domain recognition and demonstrate the utility of activation-specific
      antibodies for examining the specificity of STAT-cytokine receptor interactions.

PMID- 11290585
TI  - Core-binding factor beta (CBFbeta), but not CBFbeta-smooth muscle myosin heavy
      chain, rescues definitive hematopoiesis in CBFbeta-deficient embryonic stem
      cells.
AB  - Core-binding factor beta (CBFbeta) is the non-DNA-binding subunit of the
      heterodimeric CBFs. Genes encoding CBFbeta (CBFB), and one of the DNA-binding
      CBFalpha subunits, Runx1 (also known as CBFalpha2, AML1, and PEBP2alphaB), are
      required for normal hematopoiesis and are also frequent targets of chromosomal
      translocations in acute leukemias in humans. Homozygous disruption of either the
      Runx1 or Cbfb gene in mice results in embryonic lethality at midgestation due to
      hemorrhaging in the central nervous system, and severely impairs fetal liver
      hematopoiesis. Results of this study show that Cbfb-deficient mouse embryonic
      stem (ES) cells can differentiate into primitive erythroid colonies in vitro, but
      are impaired in their ability to produce definitive erythroid and myeloid
      colonies, mimicking the in vivo defect. Definitive hematopoiesis is restored by
      ectopic expression of full-length Cbfb transgenes, as well as by a transgene
      encoding only the heterodimerization domain of CBFbeta. In contrast, the CBFbeta
      smooth muscle myosin heavy chain (SMMHC) fusion protein generated by the inv(16)
      associated with acute myeloid leukemias (M4Eo) cannot rescue definitive
      hematopoiesis by Cbfb-deficient ES cells. Sequences responsible for the inability
      of CBFbeta-SMMHC to rescue definitive hematopoiesis reside in the SMMHC portion
      of the fusion protein. Results also show that the CBFbeta-SMMHC fusion protein
      transdominantly inhibits definitive hematopoiesis, but not to the same extent as
      homozygous loss of Runx1 or Cbfb. CBFbeta-SMMHC preferentially inhibits the
      differentiation of myeloid lineage cells, while increasing the number of
      blastlike cells in culture.

PMID- 11290586
TI  - Resolution of pluripotential intermediates in murine hematopoietic
      differentiation by global complementary DNA amplification from single cells:
      confirmation of assignments by expression profiling of cytokine receptor
      transcripts.
AB  - Although hematopoiesis is known to proceed from stem cells through a graded
      series of multipotent, oligopotent, and unipotent precursor cells, it has been
      difficult to resolve these cells physically one from another. There is,
      therefore, corresponding uncertainty about the exact distribution and timing of
      the expression of genes known to be important in hematopoietic differentiation.
      In earlier work, the generation of a set of amplified complementary DNAs (cDNAs)
      from single precursor cells was described, whose biologic potential was
      determined by the outcome of cultured sibling cells. In this study, the new
      acquisition of cDNA from multipotent myeloid precursor cells is described, as is
      the mapping of RNA-level expression of 17 distinct cytokine receptors (c-kit, Flk
      1, Flk-2/Flt-3, c-fms, gp130, erythropoietin receptor, GM-CSFRalpha, G-CSFR,
      TNFR1, IL-1RI, IL-1RII, IL-2Rbeta, IL-3-specific beta receptor, IL-4R, IL
      6Ralpha, IL-7Ralpha, and IL-11Ralpha) to the enlarged sample set, spanning stages
      from pentapotent precursors through oligopotent intermediates to committed and
      maturing cells in the myeloid and lymphoid lineages. Although the enhanced scope
      and resolving power of the analysis yielded previously unreported observations,
      there was overall agreement with known biologic responsiveness at individual
      stages, and major contradictions did not arise. Moreover, each precursor category
      displayed a unique overall pattern of hybridization to the matrix of 17 receptor
      probes, supporting the notion that each sample pool indeed reflected a unique
      precursor stage. Collectively, the results provide supportive evidence for the
      validity of the cDNA assignments to particular stages, the depth of the
      information captured, and the unique capacity of the sample matrix to resolve
      individual stages in the hematopoietic hierarchy.

PMID- 11290587
TI  - Overexpression of suppressor of cytokine signaling-1 impairs pre-T-cell receptor
      induced proliferation but not differentiation of immature thymocytes.
AB  - Cytokines play an essential role during early T-cell development. However, the
      mechanisms controlling cytokine signaling in developing thymocytes have not been
      elucidated. Cytokine receptor signaling can be modulated by suppressor of
      cytokine signaling-1 (SOCS-1), which acts as a negative regulator of Janus
      kinases. SOCS-1 is normally expressed throughout thymocyte development; however,
      retroviral-mediated overexpression of SOCS-1 in fetal liver-derived hematopoietic
      progenitors prevented their progression beyond the earliest stage of T-cell
      development. Further analysis revealed that SOCS-1 expression is transiently
      suppressed following pre-T-cell receptor (TCR) signaling. Moreover, constitutive
      expression of SOCS-1 abrogated pre-TCR- mediated expansion of immature thymocytes
      but did not interfere with differentiation. These findings reveal that SOCS-1
      serves to regulate cytokine signaling at critical checkpoints during early T-cell
      development.

PMID- 11290588
TI  - Cyclophosphamide/granulocyte colony-stimulating factor causes selective
      mobilization of bone marrow hematopoietic stem cells into the blood after M phase
      of the cell cycle.
AB  - Cytokine-mobilized peripheral blood hematopoietic stem cells (MPB HSC) are widely
      used for transplantation in the treatment of malignancies, but the mechanism of
      HSC mobilization is unclear. Although many HSC in bone marrow (BM) cycle rapidly
      and expand their numbers in response to cytoreductive agents, such as
      cyclophosphamide (CY), and cytokines, such as granulocyte colony-stimulating
      factor (G-CSF), MPB HSC are almost all in the G(0) or G(1) phase of the cell
      cycle. This has raised the question of whether a subset of noncycling BM HSC is
      selectively released, or whether cycling BM HSC are mobilized after M phase, but
      before the next S phase of the cell cycle. To distinguish between these
      possibilities, mice were treated with one dose of CY followed by daily doses of G
      CSF, and dividing cells were marked by administration of bromodeoxyuridine (BrdU)
      during the interval that BM HSC are expanding. After CY and 4 days of G-CSF,
      98.5% of the 2n DNA content long-term repopulating MPB (LT)-HSC stained
      positively for BrdU, and therefore derived from cells that divided during the
      treatment interval. Next, LT-HSC from mice previously treated with a single dose
      of CY, which kills cycling cells, and 3 daily doses of G-CSF, were nearly all
      killed by a second dose of CY, suggesting that CY/G-CSF causes virtually all LT
      HSC to cycle. Analysis of cyclin D2 messenger RNA (mRNA) expression and total RNA
      content of MPB HSC suggests that these cells are mostly in G(1) phase. After CY/G
      CSF treatment, virtually all BM LT-HSC enter the cell cycle; some of these HSC
      then migrate into the blood, specifically after M phase, and are rapidly
      recruited to particular hematopoietic organs.

PMID- 11290589
TI  - Overexpression of HOXA10 perturbs human lymphomyelopoiesis in vitro and in vivo.
AB  - Several studies point to multiple members of the Hox transcription factor family
      as playing key roles in normal hematopoietic development, and they link the
      imbalanced expression of these transcription factors, in particular of the Abd
      like A cluster HOX genes HOXA9 and HOXA10, to leukemogenesis. To test directly
      the hypothesis that HOXA10 is involved in human hematopoietic development, the
      gene was retrovirally overexpressed in human highly purified CD34(+)/GFP(+)
      hematopoietic progenitor cells derived from cord blood or fetal liver sources,
      and the impact of aberrant gene expression was analyzed on differentiation and
      proliferation in vitro and in vivo. HOXA10 misexpression profoundly impaired
      myeloid differentiation with a higher yield of blast cells in liquid culture and
      a greater than 100-fold increased generation of blast colonies after in vitro
      expansion or after replating of primary colonies first plated in methylcellulose
      directly after transduction (P < .01). Furthermore, aberrant HOXA10 expression
      almost completely blocked erythroid differentiation in methylcellulose (P < .02).
      HOXA10 deregulation also severely perturbed the differentiation of human
      progenitors in vivo, reducing B-cell development by 70% in repopulated NOD/SCID
      mice and enhancing myelopoiesis in the transduced compartment. The data provide
      evidence that the balanced expression of HOXA10 is pivotal for normal human
      hematopoietic development and that aberrant expression of the gene contributes to
      impaired differentiation and increased proliferation of human hematopoietic
      progenitor cells. These results also provide a framework to initiate more
      detailed analyses of HOX regulatory domains and HOX cofactors in the human system
      in vitro and in vivo.

PMID- 11290590
TI  - Spatial localization of transplanted hemopoietic stem cells: inferences for the
      localization of stem cell niches.
AB  - The spatial distribution of subpopulations of hemopoietic progenitor cells
      following syngeneic transplantation was investigated at the single-cell level.
      The location of infused hemopoietic progenitor cells within the femoral bone
      marrow of nonablated recipients was determined by 5-(and-6)-carboxyfluorescein
      diacetate succinimidyl ester labeling of cells and in situ fixation by perfusion.
      Analysis performed over 15 hours after infusion demonstrated that the spatial
      distribution of transplanted marrow cells is not a random process. Although the
      majority of cells enter the bone marrow from the central marrow vessels, the
      subsequent localization within the bone marrow varied according to their
      phenotype. Candidate "stem cells" demonstrated selective redistribution and were
      significantly enriched within the endosteal region, whereas mature terminally
      differentiated and lineage-committed cells selectively redistributed away from
      the endosteal region and were predominantly in the central marrow region.
      Together, these data strongly support historical evidence of the presence of
      endosteal hemopoietic stem cell niches.

PMID- 11290591
TI  - Lineage switch induced by overexpression of Ets family transcription factor PU.1
      in murine erythroleukemia cells.
AB  - PU.1 is an Ets family transcription factor essential for myelomonocyte and B-cell
      development. We previously showed that overexpression of PU.1 in murine
      erythroleukemia (MEL) cells inhibits growth and erythroid differentiation and
      induces apoptosis of the cells. In an effort to identify target genes of PU.1
      concerning these phenomena by using a messenger RNA differential display
      strategy, we found that some myeloid-specific and lymphoid-specific genes, such
      as the osteopontin gene, are transcriptionally up-regulated in MEL cells after
      overexpression of PU.1. We then found that expression of several myelomonocyte
      specific genes, including the CAAT-enhancer-binding protein-alpha and granulocyte
      macrophage colony-stimulating factor receptor genes, was induced in MEL cells
      after overexpression of PU.1. B-cell-specific genes were also examined, and
      expression of the CD19 gene was found to be induced. Expression of the
      myelomonocyte-specific proteins CD11b and F4/80 antigen but not the B-cell
      specific proteins B220 and CD19 was also induced. After overexpression of PU.1,
      MEL cells became adherent and phagocytic and showed enhanced nitroblue
      tetrazolium reduction activity. Expression of myelomonocyte-specific and B-cell
      specific genes was not induced when a mutant PU.1 with part of the activation
      domain deleted (a change found to inhibit erythroid differentiation of MEL cells)
      was expressed. These results indicate that PU.1 induces a lineage switch in MEL
      cells toward myelomonocytic cells and that its activation domain is essential for
      this effect. The results also suggest that the pathway of the lineage switch is
      distinct from that of inhibition of erythroid differentiation in MEL cells.

PMID- 11290592
TI  - Prothrombin protects factor Xa in the prothrombinase complex from inhibition by
      the heparin-antithrombin complex.
AB  - Heparin is a commonly used anticoagulant drug. It functions primarily by
      accelerating the antithrombin inhibition of coagulation proteinases, among which
      factor Xa and thrombin are believed to be the most important targets. There are
      conflicting results as to whether anticoagulant heparins can catalyze the
      antithrombin inhibition of factor Xa in the prothrombinase complex (factor Va,
      negatively charged membrane surfaces, and calcium ion), which is the
      physiologically relevant form of the proteinase responsible for the activation of
      prothrombin to thrombin during the blood coagulation process. In this study, a
      novel assay system was developed to compare the catalytic effect of different
      molecular-weight heparins in the antithrombin inhibition of factor Xa, either in
      free form or assembled into the prothrombinase complex during the process of
      prothrombin activation. This assay takes advantage of the unique property of a
      recombinant mutant antithrombin, which, similar to the wild-type antithrombin,
      rapidly inhibits factor Xa, but not thrombin, in the presence of heparin. A
      direct prothrombinase inhibition assay, monitoring thrombin generation under near
      physiological concentrations of prothrombin and antithrombin in the presence of
      therapeutic doses of low- and high-molecular-weight heparins, indicates that
      factor Xa in the prothrombinase complex is protected from inhibition by
      antithrombin more than 1000 times, independent of the molecular size of heparin.

PMID- 11290593
TI  - Antiplatelet agents in tissue factor-induced blood coagulation.
AB  - Several platelet inhibitors were examined in a tissue factor (TF)-initiated model
      of whole blood coagulation. In vitro coagulation of human blood from normal
      donors was initiated by 25 pM TF while contact pathway coagulation was suppressed
      using corn trypsin inhibitor. Products of the reaction were analyzed by
      immunoassay. Preactivation of platelets with the thrombin receptor activation
      peptide did not influence significantly the clotting time or thrombin
      antithrombin III complex (TAT) formation. Addition of prostaglandin E(1) (5
      microM) caused a significant delay in clotting (10.0 minutes) versus control (4.3
      minutes). The prolonged clotting time is correlated with delays in platelet
      activation, formation of TAT, and fibrinopeptide A (FPA) release. In blood from
      subjects receiving acetylsalicylic acid (ASA or aspirin), none of the measured
      products of coagulation were significantly affected. Similarly, no significant
      effect was observed when 5 microM dipyridamole (Persantine) was added to the
      blood. Antagonists of the platelet integrin receptor glycoprotein (gp) IIb/IIIa
      had intermediate effects on the reaction. A 1- to 2-minute delay in clot time and
      FPA formation was observed with addition of the antibodies 7E3 and Reopro
      (abciximab) (10 microg/mL), accompanied by a 40% to 70% reduction in the maximal
      rate of TAT formation and delay in platelet activation. The cyclic heptapetide,
      Integrilin (eptifibatide), at 5 microM concentration slightly prolonged clot time
      and significantly attenuated the maximum rate of TAT formation. The disruption of
      the gpIIb/IIIa-ligand interaction not only affects platelet aggregation, but also
      decreases the rate of TF-initiated thrombin generation in whole blood,
      demonstrating a potent antithrombotic effect superimposed on the antiaggregation
      characteristics.

PMID- 11290594
TI  - Growth factor-induced angiogenesis in vivo requires specific cleavage of
      fibrillar type I collagen.
AB  - The contribution of specific type I collagen remodeling in angiogenesis was
      studied in vivo using a quantitative chick embryo assay that measures new blood
      vessel growth into well-defined fibrillar collagen implants. In response to a
      combination of basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF), a strong angiogenic response was observed, coincident with
      invasion into the collagen implants of activated fibroblasts, monocytes,
      heterophils, and endothelial cells. The angiogenic effect was highly dependent on
      matrix metalloproteinase (MMP) activity, because new vessel growth was inhibited
      by both a synthetic MMP inhibitor, BB3103, and a natural MMP inhibitor, TIMP-1.
      Multiple MMPs were detected in the angiogenic tissue including MMP-2, MMP-13, MMP
      16, and a recently cloned MMP-9-like gelatinase. Using this assay system, wild
      type collagen was compared to a unique collagenase-resistant collagen (r/r), with
      regard to the ability of the respective collagen implants to support cell
      invasion and angiogenesis. It was found that collagenase-resistant collagen
      constitutes a defective substratum for angiogenesis. In implants made with r/r
      collagen there was a substantial reduction in the number of endothelial cells and
      newly formed vessels. The presence of the r/r collagen, however, did not reduce
      the entry into the implants of other cell types, that is, activated fibroblasts
      and leukocytes. These results indicate that fibrillar collagen cleavage at
      collagenase-specific sites is a rate-limiting event in growth factor-stimulated
      angiogenesis in vivo.

PMID- 11290595
TI  - Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains
      a binding site for IgMkappa responsible for platelet agglutination in plasma and
      inducing signal transduction.
AB  - Echicetin, a heterodimeric snake C-type lectin from Echis carinatus, is known to
      bind specifically to platelet glycoprotein (GP)Ib. We now show that, in addition,
      it agglutinates platelets in plasma and induces platelet signal transduction. The
      agglutination is caused by binding to a specific protein in plasma. The protein
      was isolated from plasma and shown to cause platelet agglutination when added to
      washed platelets in the presence of echicetin. It was identified as
      immunoglobulin Mkappa (IgMkappa) by peptide sequencing and dot blotting with
      specific heavy and light chain anti-immunoglobulin reagents. Platelet
      agglutination by clustering echicetin with IgMkappa induced P-selectin expression
      and activation of GPIIb/IIIa as well as tyrosine phosphorylation of several
      signal transduction molecules, including p53/56(LYN), p64, p72(SYK), p70 to p90,
      and p120. However, neither ethylenediaminetetraacetic acid nor specific
      inhibition of GPIIb/IIIa affected platelet agglutination or activation by
      echicetin. Platelet agglutination and induction of signal transduction could also
      be produced by cross-linking biotinylated echicetin with avidin. These data
      indicate that clustering of GPIb alone is sufficient to activate platelets. In
      vivo, echicetin probably activates platelets rather than inhibits platelet
      activation, as previously proposed, accounting for the observed induction of
      thrombocytopenia.

PMID- 11290596
TI  - Expression and colocalization of cytokeratin 1 and urokinase plasminogen
      activator receptor on endothelial cells.
AB  - The cellular localization of human cytokeratin 1 (CK1), urokinase plasminogen
      activator receptor (uPAR), and gC1qR, high-molecular-weight kininogen (HK)
      binding proteins on endothelial cells, was determined. CK1 was found on the
      external membrane of nonpermeabilized endothelial cells by immunoperoxidase
      staining, immunofluorescence, and transmission electron microscopy using
      immunogold. Human umbilical vein endothelial cells (HUVECs) had 7.2 +/- 0.2 x
      10(4) specific CK1 membrane sites/cell by (125)I-F(ab')(2) anti-CK1 antibody
      binding. Flow cytometry studies confirmed the presence of CK1, uPAR, and gC1qR on
      HUVECs. On laser scanning confocal microscopy and transmission electron
      microscopy, CK1 and uPAR, but not gC1qR, colocalized on the cell surface of
      HUVECs. The HUVEC surface distribution of these proteins was distinctly different
      from that for von Willebrand factor. In competitive inhibition experiments, anti
      CK1, anti-uPAR, or anti-gC1qR blocked both biotin-HK binding and prekallikrein
      (PK) activation on HUVECs with an inhibitory concentration of 50% (IC(50)) of 300
      to 350 nM, 50 to 60 nM, or 35 to 100 nM, respectively. Also, antibodies to uPAR
      and gC1qR each inhibited 86% of kallikrein-mediated, 2-chain urokinase
      plasminogen activation, whereas antibodies to CK1 only inhibited 24% of
      plasminogen activation. On HUVECs, CK1 and uPAR, but not gC1qR, colocalized to be
      a multiprotein receptor complex for HK binding, PK activation, and 2-chain
      urokinase plasminogen activation.

PMID- 11290597
TI  - Inhibition of antigen-receptor signaling by Platelet Endothelial Cell Adhesion
      Molecule-1 (CD31) requires functional ITIMs, SHP-2, and p56(lck).
AB  - Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, CD31) is a 130-kd member
      of the immunoglobulin gene superfamily that is expressed on the surface of
      platelets, endothelial cells, myeloid cells, and certain lymphocyte subsets.
      PECAM-1 has recently been shown to contain functional immunoreceptor tyrosine
      based inhibitory motifs (ITIMs) within its cytoplasmic domain, and co-ligation of
      PECAM-1 with the T-cell antigen receptor (TCR) results in tyrosine
      phosphorylation of PECAM-1, recruitment of Src homology 2 domain-containing
      protein tyrosine phosphatase-2 (SHP-2), and attenuation of TCR-mediated cellular
      signaling. To determine the molecular basis of PECAM-1 inhibitory signaling in
      lymphocytes, the study sought to (1) establish the importance of the PECAM-1
      ITIMs for its inhibitory activity, (2) determine the relative importance of SHP-2
      versus SHP-1 in mediating the inhibitory effect of PECAM-1, and (3) identify the
      protein tyrosine kinases required for PECAM-1 tyrosine phosphorylation in T
      cells. Co-ligation of wild-type PECAM-1 with the B-cell antigen receptor
      expressed on chicken DT40 B cells resulted in a marked reduction of calcium
      mobilization-similar to previous observations in T cells. In contrast, co
      ligation of an ITIM-less form of PECAM-1 had no inhibitory effect. Furthermore,
      wild-type PECAM-1 was unable to attenuate calcium mobilization in SHP-2-deficient
      DT40 variants despite abundant levels of SHP-1 in these cells. Finally, PECAM-1
      failed to become tyrosine phosphorylated in p56(lck)-deficient Jurkat T cells.
      Together, these data provide important insights into the molecular requirements
      for PECAM-1 regulation of antigen receptor signaling.

PMID- 11290598
TI  - Stat5a regulates T helper cell differentiation by several distinct mechanisms.
AB  - We have previously shown that CD4(+) T cell-mediated allergic inflammation is
      diminished in signal transducer and activator of transcription (Stat)5a-deficient
      (Stat5a(-/-)) mice. To determine whether Stat5a regulates T helper cell
      differentiation, we studied T helper (Th)1 and Th2 cell differentiation of
      Stat5a(-/-)CD4(+) T cells at single-cell levels. First, Th2 cell differentiation
      from antigen-stimulated splenocytes was significantly decreased in Stat5a(-/-)
      mice as compared with that in wild-type mice. Further, Th2 cell differentiation
      was also impaired in Stat5a(-/-) mice even when purified CD4(+) T cells were
      stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin
      4. Moreover, the retrovirus-mediated gene expression of Stat5a in Stat5a(-/
      )CD4(+) T cells restored the Th2 cell differentiation at the similar levels to
      that in wild-type CD4(+) T cells. In addition, interleukin-4 normally
      phosphorylated Stat6 in CD4(+) T cells from Stat5a(-/-) mice. Second, the
      development of CD4(+)CD25(+) immunoregulatory T cells was impaired in Stat5a(-/-)
      mice, as indicated by a significant decrease in the number of CD4(+)CD25(+) T
      cells in Stat5a(-/-) mice. Furthermore, the depletion of CD4(+)CD25(+) T cells
      from wild-type splenocytes significantly decreased Th2 cell differentiation but
      increased Th1 cell differentiation, whereas the depletion of CD4(+)CD25(+) T
      cells from Stat5a(-/-) splenocytes had no significant effect on the Th1 and Th2
      cell differentiation. Together, these results indicate that the intrinsic
      expression of Stat5a in CD4(+) T cells is required for Th2 cell differentiation
      and that Stat5a is involved in the development of CD4(+)CD25(+) immunoregulatory
      T cells that modulate T helper cell differentiation toward Th2 cells.

PMID- 11290599
TI  - Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell
      response to viral lytic cycle proteins.
AB  - Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the
      etiologic agent of Kaposi sarcoma (KS). The natural history of primary HHV-8
      infection, including clinical outcome and host immune responses that may be
      important in preventing disease related to HHV-8, has not been elucidated. The
      present study characterized the clinical, immunologic, and virologic parameters
      of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal
      study of 108 human immunodeficiency virus type 1 seronegative men in the
      Multicenter AIDS Cohort Study. Primary HHV-8 infection was associated with mild,
      nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and
      lymphadenopathy. There were no alterations in numbers of CD4(+) or CD8(+) T cells
      or CD8(+) T-cell interferon gamma (IFN-gamma) production to mitogen or nominal
      antigen. CD8(+) cytotoxic T-lymphocyte precursor (CTLp) and IFN-gamma reactivity
      were detected during primary HHV-8 infection, with broad specificity to 5 lytic
      cycle proteins of HHV-8 encoded by open reading frame 8 (ORF 8; glycoprotein B
      homolog of Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein
      homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein
      homolog), in association with increases in serum antibody titers and appearance
      of HHV-8 DNA in blood mononuclear cells. CD8(+) T-cell responses to HHV-8
      decreased by 2 to 3 years after primary infection. This antiviral T-cell response
      may control initial HHV-8 infection and prevent development of disease.

PMID- 11290600
TI  - Targeted inhibition of calcineurin signaling blocks calcium-dependent
      reactivation of Kaposi sarcoma-associated herpesvirus.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) is associated with KS, primary
      effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV
      in latently infected cells and subsequent plasma viremia occur before the
      development of KS. Intracellular signaling pathways involved in KSHV reactivation
      were studied. In latently infected PEL cells (BCBL-1), KSHV reactivation in
      single cells was determined by quantitative flow cytometry. Viral particle
      production was determined by electron microscope analyses and detection of minor
      capsid protein in culture supernatants. Agents that mobilized intracellular
      calcium (ionomycin, thapsigargin) induced expression of KSHV lytic cycle
      associated proteins and led to increased virus production. Calcium-mediated virus
      reactivation was blocked by specific inhibitors of calcineurin-dependent signal
      transduction (cyclosporine, FK506). Similarly, calcium-mediated virus
      reactivation in KSHV-infected dermal microvascular endothelial cells was blocked
      by cyclosporine. Furthermore, retroviral transduction with plasmid DNA encoding
      VIVIT, a peptide specifically blocking calcineurin-NFAT interactions, inhibited
      calcium-dependent KSHV reactivation. By contrast, chemical induction of lytic
      phase infection by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate was
      blocked by protein kinase C inhibitors, but not by calcineurin inhibitors. In
      summary, calcineurin-dependent signal transduction, an important signaling
      cascade in vivo, induces calcium-dependent KSHV replication, providing a possible
      target for the design of antiherpesvirus strategies in KSHV-infected patients.

PMID- 11290601
TI  - Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor
      necrosis factor-alpha by blocking contact-mediated activation of monocytes by T
      lymphocytes.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta),
      essential components in the pathogenesis of immunoinflammatory diseases, are
      strongly induced in monocytes by direct contact with stimulated T lymphocytes.
      This study demonstrates that adult human serum (HS) but not fetal calf or cord
      blood serum displays inhibitory activity toward the contact-mediated activation
      of monocytes by stimulated T cells, decreasing the production of both TNF-alpha
      and IL-1beta. Fractionation of HS and N-terminal microsequencing as well as
      electroelution of material subjected to preparative electrophoresis revealed that
      apolipoprotein A-I (apo A-I), a "negative" acute-phase protein, was the
      inhibitory factor. Functional assays and flow cytometry analyses show that high
      density lipoprotein (HDL)-associated apo A-I inhibits contact-mediated activation
      of monocytes by binding to stimulated T cells, thus inhibiting TNF-alpha and IL
      1beta production at both protein and messenger RNA levels. Furthermore, apo A-I
      inhibits monocyte inflammatory functions in peripheral blood mononuclear cells
      activated by either specific antigens or lectins without affecting cell
      proliferation. These results demonstrate a new anti-inflammatory activity of HDL
      associated apo A-I that might have modulating functions in nonseptic conditions.
      Therefore, because HDL has been shown to bind and neutralize lipopolysaccharide,
      HDL appears to play an important part in modulating both acute and chronic
      inflammation. The novel anti-inflammatory function of apo A-I reported here might
      lead to new therapeutic approaches in inflammatory diseases such as rheumatoid
      arthritis, multiple sclerosis, systemic lupus erythematosus, and atherosclerosis.

PMID- 11290602
TI  - Regulation of nuclear factor of activated T cells by phosphotyrosyl-specific
      phosphatase activity: a positive effect on HIV-1 long terminal repeat-driven
      transcription and a possible implication of SHP-1.
AB  - Although protein tyrosine phosphatase (PTP) inhibitors used in combination with
      other stimuli can induce interleukin 2 (IL-2) production in T cells, a direct
      implication of nuclear factor of activated T cells (NFAT) has not yet been
      demonstrated. This study reports that exposure of leukemic T cells and human
      peripheral blood mononuclear cells to bis-peroxovanadium (bpV) PTP inhibitors
      markedly induce activation and nuclear translocation of NFAT. NFAT activation by
      bpV was inhibited by the immunosuppressive drugs FK506 and cyclosporin A, as well
      as by a specific peptide inhibitor of NFAT activation. Mobility shift assays
      showed specific induction of the NFAT1 member by bpV molecules. The bpV-mediated
      NFAT activation was observed to be important for the up-regulation of the human
      immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR) and the IL-2
      promoter; NFAT1 was demonstrated to be particularly important in bpV-dependent
      positive action on HIV-1 LTR transcription. The active participation of p56(lck),
      ZAP-70, p21(ras), and calcium in the bpV-mediated signaling cascade leading to
      NFAT activation was confirmed, using deficient cell lines and dominant-negative
      mutants. Finally, overexpression of wild-type SHP-1 resulted in a greatly
      diminished activation of NFAT by bpV, suggesting an involvement of SHP-1 in the
      regulation of NFAT activation. These data were confirmed by constitutive NFAT
      translocation observed in Jurkat cells stably expressing a dominant-negative
      version of SHP-1. The study proposes that PTP activity attenuates constitutive
      kinase activities that otherwise would lead to constant NFAT activation and that
      this activation is participating in HIV-1 LTR stimulation by PTP inhibition.

PMID- 11290603
TI  - Analysis of BCL-6 mutations in classic Hodgkin disease of the B- and T-cell type.
AB  - BCL-6 is essential for germinal center formation and thus for affinity maturation
      of immunoglobulin (Ig) genes by somatic mutations. The 5'-noncoding region of the
      BCL-6 gene is even a target for the mutation machinery. Translocations of the BCL
      6 gene to heterologous promoters and mutations of its 5'-noncoding regulatory
      region were reported to be potential mechanisms for deregulating BCL-6 expression
      and for playing a role in the genesis of non-Hodgkin lymphoma. In line with this
      hypothesis is the observation that B-cell lymphoma with somatic mutations, such
      as diffuse large B-cell lymphoma and follicular lymphoma, also carry BCL-6
      mutations, some of which are recurrently detectable. Classic Hodgkin disease
      (cHD) is also derived from B cells with high loads of somatic mutations and thus
      a further candidate for BCL-6 mutations. To determine the presence and potential
      role of BCL-6 mutations in cHD, the 5'-noncoding BCL-6 proportion of single
      Hodgkin and Reed-Sternberg (HRS) cells from 6 cases of cHD and 6 cases of HD
      derived cell lines was analyzed. All B-cell-derived HD cases and cell lines
      harbored BCL-6 mutations. In contrast, both T-cell-derived HD cases and cell
      lines were devoid of BCL-6 mutations. With only one exception, there were no
      lymphoma-specific recurrent BCL-6 mutations detected, and BCL-6 protein was
      absent from the HRS cells of most cases. In conclusion, (1) somatic BCL-6
      mutations are restricted to cHD cases of B-cell origin, and (2) the BCL-6
      mutations represent mostly irrelevant somatic base substitutions without
      consequences for BCL-6 protein expression and the pathogenesis of cHD.

PMID- 11290604
TI  - A model of human p210(bcr/ABL)-mediated chronic myelogenous leukemia by
      transduction of primary normal human CD34(+) cells with a BCR/ABL-containing
      retroviral vector.
AB  - Most insights into the molecular mechanisms underlying transformation by the
      p210(BCR/ABL) oncoprotein are derived from studies in which BCR/ABL cDNA was
      introduced into hematopoietic or fibroblast cell lines. However, such cell line
      models may not represent all the features of chronic myelogenous leukemia (CML)
      caused by additional genetic abnormalities and differences in the biology of cell
      lines compared with primary hematopoietic progenitor and stem cells. A primary
      human hematopoietic progenitor cell model for CML was developed by the
      transduction of b3a2 BCR/ABL cDNA in normal CD34(+) cells. Adhesion of BCR/ABL
      transduced CD34(+) cells to fibronectin was decreased, but migration over
      fibronectin was enhanced compared with that of mock-transduced CD34(+) cells.
      Adhesion to fibronectin did not decrease the proliferation of BCR/ABL-transduced
      CD34(+) cells but decreased the proliferation of mock-transduced CD34(+) cells.
      This was associated with elevated levels of p27(Kip) in p210(BCR/ABL)-expressing
      CD34(+) cells. In addition, the presence of p210(BCR/ABL) delayed apoptosis after
      the withdrawal of cytokines and serum. Finally, significantly more and larger
      myeloid colony-forming units grew from BCR/ABL than from mock-transduced CD34(+)
      cells. Thus, the transduction of CD34(+) cells with the b3a2-BCR/ABL cDNA
      recreates most, if not all, phenotypic abnormalities seen in primary CML CD34(+)
      cells. This model should prove useful for the study of molecular mechanisms
      associated with the presence of p210(BCR/ABL) in CML.

PMID- 11290605
TI  - The myeloma-associated oncogene fibroblast growth factor receptor 3 is
      transforming in hematopoietic cells.
AB  - Translocations involving fibroblast growth factor receptor 3 (fgfr3) have been
      identified in about 25% of patients with myeloma. To directly examine the
      oncogenic potential of fgfr3, murine bone marrow (BM) cells were transduced with
      retroviral vectors containing either wild-type fgfr3 or an activated mutant form
      of the receptor, fgfr3-TD. Mice transplanted with FGFR3-TD-expressing BM
      developed a marked leukocytosis and lethal hematopoietic cell infiltration of
      multiple tissues within 6 weeks of transplantation. Secondary and tertiary
      recipients of spleen or BM from primary fgfr3-TD mice also developed tumors
      within 6 to 8 weeks. Analysis of the circulating tumor cells revealed a pre-B
      cell phenotype in most mice, although immature T-lymphoid or mature myeloid
      populations also predominated in some animals. Enhanced lymphoid but not myeloid
      colony formation was observed in the early posttransplantation period and only
      interleukin 7 and FGF-responsive pre-B-cell lines could be established from
      tumors. Cell expansions in primary recipients appeared polyclonal, whereas tumors
      in later passages exhibited either clonal B- or T-cell receptor gene
      rearrangements. Mice transplanted with wild-type FGFR3-expressing BM developed
      delayed pro-B-cell lymphoma/leukemias approximately 1 year after transplantation.
      These studies confirm that FGFR3 is transforming and can produce lymphoid
      malignancies in mice.

PMID- 11290606
TI  - The combination of chemotherapy and systemic immunotherapy with soluble B7
      immunoglobulin G leads to cure of murine leukemia and lymphoma and demonstration
      of tumor-specific memory responses.
AB  - Major mechanisms underlying poor immune responses to autologous tumor-associated
      antigens are overwhelming tumor kinetics and the absence of effective T-cell
      costimulation by antigen-presenting cells. To address these issues, leukemia and
      lymphoma mice were treated with the combination of chemotherapy and systemic
      immunotherapy with recombinant soluble murine B7-immunoglobulin G (IgG)
      molecules. In this report, 3 murine models were used, a radiation-induced SJL
      acute myeloid leukemia, a transplantable spontaneous SJL lymphoma, and the
      C57BL/6 EL-4 thymic lymphoma. Various treatment modalities were evaluated: single
      treatments with either B7-IgG or chemotherapy as well as combination therapies.
      The results demonstrate the following: (1) in all tumor models, the combination
      of chemotherapy and soluble B7-IgGs is more potent than either therapy alone,
      leading to cure of tumor-bearing animals; (2) the therapeutic responses are T
      cell-dependent, because combined therapy is not efficacious in severe combined
      immunodeficient mice; (3) the rejection of tumor cells leads to the development
      of tumor-specific immunity, because cured mice are immune to the rejected tumor
      but not to a different syngeneic tumor; and (4) (51)Cr release assays show that
      rejection of tumor cells leads to the development of very potent tumor-specific
      cytotoxic T-lymphocyte activity. On the basis of these results, it is proposed
      that chemotherapy-mediated tumor reduction, together with consequent augmented
      tumor-antigen presentation to activated T cells, are primary mechanisms leading
      to curative responses. The safety profile of the B7-IgG fusion proteins and their
      synergy with chemotherapy strongly suggest that the combination regimen is a
      promising strategy in cancer treatment.

PMID- 11290607
TI  - Novel vitamin D(3) analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D(3), that
      modulates cell growth, differentiation, apoptosis, cell cycle, and induction of
      PTEN in leukemic cells.
AB  - The active form of vitamin D(3), 1,25(OH)(2)D(3), inhibits proliferation and
      induces differentiation of a variety of malignant cells. A new class of vitamin
      D(3) analogs, having 2 identical side chains attached to carbon-20, was
      synthesized and the anticancer effects evaluated. Four analogs were evaluated for
      their ability to inhibit growth of myeloid leukemia (NB4, HL-60), breast (MCF-7),
      and prostate (LNCaP) cancer cells. All 4 analogs inhibited growth in a dose
      dependent manner. Most effective was 21-(3-methyl-3-hydroxy-butyl)-19-nor D(3)
      (Gemini-19-nor), which has 2 side chains and removal of the C-19. Gemini-19-nor
      was approximately 40 625-, 70-, 23-, and 380-fold more potent than
      1,25(OH)(2)D(3) in inhibiting 50% clonal growth (ED(50)) of NB4, HL-60, MCF-7,
      and LNCaP cells, respectively. Gemini-19-nor (10(-8) M) strongly induced
      expression of CD11b and CD14 on HL-60 cells (90%); in contrast, 1,25(OH)(2)D(3)
      (10(-8) M) stimulated only 50% expression. Annexin V assay showed that Gemini-19
      nor and 1,25(OH)(2)D(3) induced apoptosis in a dose-dependent fashion. Gemini-19
      nor (10(-8) M, 4 days) caused apoptosis in approximately 20% of cells, whereas
      1,25(OH)(2)D(3) at the same concentration did not induce apoptosis. Gemini-19-nor
      increased in HL-60 both the proportion of cells in the G(1)/G(0) phase and
      expression level of p27(kip1). Moreover, Gemini-19-nor stimulated expression of
      the potential tumor suppressor, PTEN. Furthermore, other inducers of
      differentiation, all-trans-retinoic acid and 12-O-tetradecanoylphorbol 13
      acetate, increased PTEN expression in HL-60. In summary, Gemini-19-nor strongly
      inhibited clonal proliferation in various types of cancer cells, especially NB4
      cells, suggesting that further studies to explore its anticancer potential are
      warranted. In addition, PTEN expression appears to parallel terminal
      differentiation of myeloid cells.

PMID- 11290608
TI  - Activating mutation of D835 within the activation loop of FLT3 in human
      hematologic malignancies.
AB  - Mutations of receptor tyrosine kinases are implicated in the constitutive
      activation and development of human malignancy. An internal tandem duplication
      (ITD) of the juxtamembrane (JM) domain-coding sequence of the FLT3 gene
      (FLT3/ITD) is found in 20% of patients with acute myeloid leukemia (AML) and is
      strongly associated with leukocytosis and a poor prognosis. On the other hand,
      mutations of the c-KIT gene, which have been found in mast cell leukemia and AML,
      are clustered in 2 distinct regions, the JM domain and D816 within the activation
      loop. This study was designed to analyze the mutation of D835 of FLT3, which
      corresponds to D816 of c-KIT, in a large series of human hematologic
      malignancies. Several kinds of missense mutations were found in 30 of the 429
      (7.0%) AML cases, 1 of the 29 (3.4%) myelodysplastic syndrome (MDS) cases, and 1
      of the 36 (2.8%) acute lymphocytic leukemia patients. The D835Y mutation was most
      frequently found (22 of the 32 D835 mutations), followed by the D835V (5), and
      D835H (1), D835E (1), and D835N (1) mutations. Of note is that D835 mutations
      occurred independently of FLT3/ITD. An analysis in the 201 patients newly
      diagnosed with AML (excluding M3) revealed that, in contrast to the FLT3/ITD
      mutation (n = 46), D835 mutations (n = 8) were not significantly related to the
      leukocytosis, but tended to worsen disease-free survival. All D835-mutant FLT3
      were constitutively tyrosine-phosphorylated and transformed 32D cells, suggesting
      these mutations were constitutively active. These results demonstrate that the
      FLT3 gene is the target most frequently mutated to become constitutively active
      in AML.

PMID- 11290609
TI  - ARG tyrosine kinase activity is inhibited by STI571.
AB  - The tyrosine kinase inhibitor STI571 inhibits BCR/ABL and induces hematologic
      remission in most patients with chronic myeloid leukemia. In addition to BCR/ABL,
      STI571 also inhibits v-Abl, TEL/ABL, the native platelet-derived growth factor
      (PDGF)beta receptor, and c-KIT, but it does not inhibit SRC family kinases, c
      FMS, FLT3, the epidermal growth factor receptor, or multiple other tyrosine
      kinases. ARG is a widely expressed tyrosine kinase that shares substantial
      sequence identity with c-ABL in the kinase domain and cooperates with ABL to
      regulate neurulation in the developing mouse embryo. As described here, ARG has
      recently been implicated in the pathogenesis of leukemia as a fusion partner of
      TEL. A TEL/ARG fusion was constructed to determine whether ARG can be inhibited
      by STI571. When expressed in the factor-dependent murine hematopoietic cell line
      Ba/F3, the TEL/ARG protein was heavily phosphorylated on tyrosine, increased
      tyrosine phosphorylation of multiple cellular proteins, and induced factor
      independent proliferation. The effects of STI571 on Ba/F3 cells transformed with
      BCR/ABL, TEL/ABL, TEL/PDGFbetaR, or TEL/ARG were then compared. STI571 inhibited
      tyrosine phosphorylation and cell growth of Ba/F3 cells expressing BCR/ABL,
      TEL/ABL, TEL/PDGFbetaR, and TEL/ARG with an IC(50) of approximately 0.5 microM in
      each case, but it had no effect on untransformed Ba/F3 cells growing in IL-3 or
      on Ba/F3 cells transformed by TEL/JAK2. Culture of TEL/ARG-transfected Ba/F3
      cells with IL-3 completely prevented STI571-induced apoptosis in these cells,
      similar to what has been observed with BCR/ABL- or TEL/ABL-transformed cells.
      These results indicate that ARG is a target of the small molecule, tyrosine
      kinase inhibitor STI571.

PMID- 11290610
TI  - Myeloblastin is an Myb target gene: mechanisms of regulation in myeloid leukemia
      cells growth-arrested by retinoic acid.
AB  - A pivotal role has been assigned to Myb in the control of myeloid cell growth.
      Although Myb is a target of retinoic acid, little is known about the mechanisms
      by which it may contribute to induced growth arrest in leukemia cells. Indeed,
      few Myb target genes are known to be linked to proliferation. Myeloblastin is
      involved in the control of proliferation in myeloid leukemia cells. It is
      expressed early during hematopoiesis and is a granulocyte colony-stimulating
      factor-responsive gene. Myeloblastin can confer factor-independent growth to
      hematopoietic cells, an early step in leukemia transformation. The myeloblastin
      promoter contains PU.1, C/EBP, and Myb binding sites, each of which are critical
      for constitutive expression in myeloid cells. Inhibition of myeloblastin
      expression in leukemia cells growth-arrested by retinoic acid is demonstrated to
      depend on Myb down-regulation. Myb is shown to induce myeloblastin expression and
      abolish its down-regulation by retinoic acid. Altogether, the data offer a clue
      as to how a myeloid-specific transcriptional machinery can be accessible to
      regulation by retinoic acid and point to myeloblastin as a novel target of Myb.
      This link between Myb and myeloblastin suggests a previously nonidentified Myb
      pathway through which growth arrest is induced by retinoic acid in myeloid
      leukemia cells.

PMID- 11290611
TI  - RNA expression patterns change dramatically in human neutrophils exposed to
      bacteria.
AB  - A comprehensive study of changes in messenger RNA (mRNA) levels in human
      neutrophils following exposure to bacteria is described. Within 2 hours there are
      dramatic changes in the levels of several hundred mRNAs including those for a
      variety of cytokines, receptors, apoptosis-regulating products, and membrane
      trafficking regulators. In addition, there are a large number of up-regulated
      mRNAs that appear to represent a common core of activation response genes that
      have been identified as early-response products to a variety of stimuli in a
      number of other cell types. The activation response of neutrophils to
      nonpathogenic bacteria is greatly altered by exposure to Yersinia pestis, which
      may be a major factor contributing to the virulence and rapid progression of
      plague. Several gene clusters were created based on the patterns of gene
      induction caused by different bacteria. These clusters were consistent with those
      found by a principal components analysis. A number of the changes could be
      interpreted in terms of neutrophil physiology and the known functions of the
      genes. These findings indicate that active regulation of gene expression plays a
      major role in the neutrophil contribution to the cellular inflammatory response.
      Interruption of these changes by pathogens, such as Y pestis, could be
      responsible, at least in part, for the failure to contain infections by highly
      virulent organisms.

PMID- 11290612
TI  - Activation and priming of neutrophil nicotinamide adenine dinucleotide phosphate
      oxidase and phospholipase A(2) are dissociated by inhibitors of the kinases
      p42(ERK2) and p38(SAPK) and by methyl arachidonyl fluorophosphonate, the dual
      inhibitor of cytosolic and calcium-independent phospholipase A(2).
AB  - Arachidonic acid (AA) generated by phospholipase A(2) (PLA(2)) is thought to be
      an essential cofactor for phagocyte nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase activity. Both enzymes are simultaneously primed by cytokines
      such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor
      necrosis factor-alpha (TNF-alpha). The possibility that either unprimed or
      cytokine-primed responses of PLA(2) or NADPH oxidase to the chemotactic agents
      formyl-methionyl-leucyl-phenylalanine (FMLP) and complement factor 5a (C5a) could
      be differentially inhibited by inhibitors of the mitogen-activated protein (MAP)
      kinase family members p42(ERK2) (PD98059) and p38(SAPK) (SB203580) was
      investigated. PD98059 inhibited the activation of p42(ERK2) by GM-CSF, TNF-alpha,
      and FMLP, but it did not inhibit FMLP-stimulated superoxide production in either
      unprimed or primed neutrophils. There was no significant arachidonate release
      from unprimed neutrophils stimulated by FMLP, and arachidonate release stimulated
      by calcium ionophore A23187 was not inhibited by PD98059. In contrast, PD98059
      inhibited both TNF-alpha- and GM-CSF-primed PLA(2) responses stimulated by FMLP.
      On the other hand, SB203580 inhibited FMLP-superoxide responses in unprimed as
      well as TNF-alpha- and GM-CSF-primed neutrophils, but failed to inhibit TNF-alpha
      and GM-CSF-primed PLA(2) responses stimulated by FMLP, and additionally enhanced
      A23187-stimulated arachidonate release, showing that priming and activation of
      PLA(2) and NADPH oxidase are differentially dependent on both the p38(SAPK) and
      p42(ERK2) pathways. Studies using C5a as an agonist gave similar results and
      confirmed the findings with FMLP. In addition, methyl arachidonyl
      fluorophosphonate (MAFP), the dual inhibitor of c and iPLA(2) enzymes, failed to
      inhibit superoxide production in primed cells at concentrations that inhibited
      arachidonate release. These data demonstrate that NADPH oxidase activity can be
      dissociated from AA generation and indicate a more complex role for arachidonate
      in neutrophil superoxide production.

PMID- 11290613
TI  - Mac-1 (CD11b/CD18) is essential for Fc receptor-mediated neutrophil cytotoxicity
      and immunologic synapse formation.
AB  - Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of
      antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1
      (complement receptor type 3, CD11b/CD18) has previously been implicated in
      receptor cooperation with Fc receptors (FcRs). The role of Mac-1 in FcR-mediated
      lysis of tumor cells was characterized by studying normal human PMNs, Mac-1
      deficient mouse PMNs, and mouse PMNs transgenic for human FcR. All PMNs
      efficiently phagocytosed Ab-coated particles. However, antibody-dependent
      cellular cytotoxicity (ADCC) was abrogated in Mac-1(-/-) PMNs and in human PMNs
      blocked with anti-Mac-1 monoclonal Ab (mAb). Mac-1(-/-) PMNs were unable to
      spread on Ab-opsonized target cells and other Ab-coated surfaces. Confocal laser
      scanning and electron microscopy revealed a striking difference in immunologic
      synapse formation between Mac-1(-/-) and wild-type PMNs. Also, respiratory burst
      activity could be measured outside membrane-enclosed compartments by using Mac-1(
      /-) PMNs bound to Ab-coated tumor cells, in contrast to wild-type PMNs. In
      summary, these data document an absolute requirement of Mac-1 for FcR-mediated
      PMN cytotoxicity toward tumor targets. Mac-1(-/-) PMNs exhibit defective
      spreading on Ab-coated targets, impaired formation of immunologic synapses, and
      absent tumor cytolysis.

PMID- 11290614
TI  - Phorbol ester up-regulates capacities for nuclear translocation and
      phosphorylation of 5-lipoxygenase in Mono Mac 6 cells and human polymorphonuclear
      leukocytes.
AB  - The leukotrienes are inflammatory mediators derived from arachidonic acid. It was
      demonstrated that the priming of leukocytes with phorbol-12-myristate-13-acetate
      (PMA) leads to the increased formation of 5-lipoxygenase (5-LO) products in
      parallel with the increased association of 5-LO with the nucleus and the
      activation of kinases that can phosphorylate 5-LO in vitro. Stimulation of the
      monocytic cell line Mono Mac 6 with calcium ionophore gave low 5-LO product
      formation and no detectable redistribution of 5-LO. However, after priming of
      Mono Mac 6 cells with phorbol esters, ionophore led to the association of 45% to
      75% of cellular 5-LO with the nuclear membrane, to 5-LO kinase activation, to
      enhanced release of arachidonate, and to substantial leukotriene synthesis.
      Similar results were obtained for human polymorphonuclear leukocytes stimulated
      with low-dose ionophore. In addition, for each cell type, PMA priming up
      regulated leukotriene biosynthesis in the presence of exogenous arachidonic acid.
      A protein kinase inhibitor, calphostin C, reduced the association of 5-LO with
      the nucleus and 5-LO kinase activity, and the formation of 5-LO products was
      inhibited. These results suggest that PMA up-regulates leukotriene biosynthesis
      not only by increasing the release of endogenous arachidonate, but also by
      increasing the capacity for 5-LO phosphorylation and for the translocation of 5
      LO to the nucleus in leukocytes.

PMID- 11290615
TI  - Coexpression of band 3 mutants and Rh polypeptides: differential effects of band
      3 on the expression of the Rh complex containing D polypeptide and the Rh complex
      containing CcEe polypeptide.
AB  - K562 cells were stably transfected with cDNAs encoding the band 3 found in
      Southeast Asian ovalocytosis (B3SAO, deletion of residues 400-408), band 3 with a
      transport-inactivating E681Q point mutation (B3EQ), or normal band 3 (B3). Flow
      cytometric analysis and quantitative immunoblotting revealed that B3SAO expressed
      alone was translocated to the plasma membrane, at levels similar to B3 or B3EQ.
      Nine monoclonal antibodies that reacted with extracellular loops of B3 also
      reacted with B3SAO, although the affinity of most antibodies for the mutant
      protein was reduced. Both known Wr(b) epitopes were expressed on K562/B3SAO
      cells, demonstrating that B3SAO interacts with glycophorin A. The growth rates of
      K562 clones expressing equivalent amounts of B3 and B3EQ were the same,
      suggesting that the potentially toxic transport function of band 3 may be
      regulated in K562 cells. The band 3-mediated enhancement of Rh antigen reactivity
      and the depression of Rh epitopes on SAO erythrocytes were investigated by
      comparing the coexpression of B3, B3SAO, or B3EQ in K562 clones expressing
      exogenous RhcE or RhD polypeptides. The results are consistent with an
      interaction between band 3 and the Rh polypeptide-Rh glycoprotein (RhAG) complex,
      which may enhance translocation of the complex or affect its conformation in the
      plasma membrane. The data suggest that the interaction between band 3 and the RhD
      RhAG complex is weaker than it is between band 3 and the RhCcEe-RhAG complex.

PMID- 11290616
TI  - Protection from lethal murine graft-versus-host disease without compromise of
      alloengraftment using transgenic donor T cells expressing a thymidine kinase
      suicide gene.
AB  - Donor T cells play a pivotal role in facilitating alloengraftment but also cause
      graft-versus-host disease (GVHD). Ex vivo T-cell depletion (TCD) of donor marrow
      is the most effective strategy for reducing GVHD but can compromise engraftment.
      This study examined an approach whereby donor T cells are selectively eliminated
      in vivo after transplantation using transgenic mice in which a thymidine kinase
      (TK) suicide gene is targeted to the T cell using a CD3 promoter/enhancer
      construct. Lethally irradiated B10.BR mice transplanted with major
      histocompatibility complex (MHC)-incompatible TCD C57BL/6 (B6) bone marrow (BM)
      plus TK(+) T cells were protected from GVHD after treatment with ganciclovir
      (GCV) in a schedule-dependent fashion. To examine the effect of GCV treatment on
      alloengraftment, sublethally irradiated AKR mice underwent transplantation with
      TCD B6 BM plus limiting numbers (5 x 10(5)) of B6 TK(+) T cells. Animals treated
      with GCV had comparable donor engraftment but significantly reduced GVHD when
      compared with untreated mice. These mice also had a significantly increased
      number of donor splenic T cells when assessed 4 weeks after bone marrow
      transplantation. Thus, the administration of GCV did not render recipients T-cell
      deficient, but rather enhanced lymphocyte recovery. Adoptive transfer of spleen
      cells from GCV-treated chimeric mice into secondary AKR recipients failed to
      cause GVHD indicating that donor T cells were tolerant of recipient alloantigens.
      These studies demonstrate that administration of TK gene-modified donor T cells
      can be used as an approach to mitigate GVHD without compromising alloengraftment.

PMID- 11290617
TI  - Postgrafting administration of granulocyte colony-stimulating factor impairs
      functional immune recovery in recipients of human leukocyte antigen haplotype
      mismatched hematopoietic transplants.
AB  - In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell
      depletion prevents graft-versus-host disease (GVHD) but delays immune recovery.
      Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem
      cells and to recipients to ensure engraftment. Studies have shown that G-CSF
      promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not
      protect against intracellular pathogens and fungi. The effect of administration
      of G-CSF to recipients of mismatched hematopoietic transplants with respect to
      transplantation outcome and functional immune recovery was investigated. In 43
      patients with acute leukemia who received G-CSF after transplantation, the
      engraftment rate was 95%. However, the patients had a long-lasting type 2 immune
      reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12)
      and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the
      IL-12 receptor beta(2) chain. Similar immune reactivity patterns were observed on
      exposure of donor cells to G-CSF. Elimination of postgrafting administration of G
      CSF in a subsequent series of 36 patients with acute leukemia, while not
      adversely affecting engraftment rate (93%), resulted in the anticipated
      appearance of IL-12-producing dendritic cells (1-3 months after transplantation
      versus > 12 months in transplant recipients given G-CSF), of CD4(+) cells of a
      mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover,
      CD4(+) cell counts increased in significantly less time. Finally, elimination of
      G-CSF-mediated immune suppression did not significantly increase the incidence of
      GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients
      of T-cell-depleted hematopoietic transplants was associated with abnormal antigen
      presenting cell functions and T-cell reactivity. Elimination of postgrafting
      administration of G-CSF prevented immune dysregulation and accelerated functional
      immune recovery.

PMID- 11290618
TI  - A high bone marrow plasma cell labeling index in stable plateau-phase multiple
      myeloma is a marker for early disease progression and death.
AB  - The plasma cell labeling index (PCLI) is a measure of plasma cell proliferative
      activity and is an important prognostic factor in newly diagnosed multiple
      myeloma (MM). Occasionally patients have been observed with stable, plateau phase
      MM with minimal numbers of residual light-chain-restricted monoclonal plasma
      cells, but a high PCLI. No data are available on the outcomes for such patients.
      Data from 57 patients with plateau phase MM and a marrow PCLI of more than 1.0%
      were compared with 105 matched control patients with MM with a marrow PCLI of
      less than 1.0%. All patients had less than 10% total plasma cells on marrow
      aspirate and biopsy. The median time to progression and overall survival were 8
      months and 20 months, respectively, in the high PCLI group versus 39 months and
      56 months, respectively, in the low PCLI group (P < .0001). These findings
      suggest that a high PCLI in patients with apparently stable, plateau phase MM is
      an adverse parameter that may predict a short time to disease progression and
      death.

PMID- 11290619
TI  - A new beginning for care for elderly people?

PMID- 11290620
TI  - Fatigue: time to recognise and deal with an old problem.

PMID- 11290622
TI  - Obtaining consent for examination and treatment.

PMID- 11290621
TI  - Home delivery: chemotherapy and pizza?

PMID- 11290623
TI  - The anaemia of chronic disease.

PMID- 11290624
TI  - Scientists attack Bush over U turn on climate change treaty.

PMID- 11290625
TI  - New centre to investigate global health threats.

PMID- 11290626
TI  - Using patient identifiable data without consent. Integrity of communicable
      disease surveillance is important patient care.

PMID- 11290627
TI  - Spanish sex workers forced to carry health check cards.

PMID- 11290628
TI  - Postherpetic neuralgia. Pathogenesis of postherpetic neuralgia should be
      determined.

PMID- 11290629
TI  - Down's children received "less favourable" hospital treatment.

PMID- 11290630
TI  - US considers medical role for marijuana.

PMID- 11290631
TI  - US judges rule in favour of abortion "hit list".

PMID- 11290632
TI  - Could fewer islet cells be transplanted in type 1 diabetes? Insulin independence
      should be dominant force in islet transplantation.

PMID- 11290633
TI  - Longitudinal cohort study of childhood IQ and survival up to age 76.
AB  - OBJECTIVES: To test the association between childhood IQ and mortality over the
      normal human lifespan. DESIGN: Longitudinal cohort study. SETTING: Aberdeen.
      SUBJECTS: All 2792 children in Aberdeen born in 1921 and attending school on 1
      June 1932 who sat a mental ability test as part of the Scottish mental survey
      1932. MAIN OUTCOME MEASURE: Survival at 1 January 1997. RESULTS: 79.9% (2230) of
      the sample was traced. Childhood mental ability was positively related to
      survival to age 76 years in women (P<0.0001) and men (P<0.0001). A 15 point
      disadvantage in mental ability at age 11 conferred a relative risk of 0.79 of
      being alive 65 years later (95% confidence interval 0.75 to 0.84); a 30 point
      disadvantage reduced this to 0.63 (0.56 to 0.71). However, men who died during
      active service in the second world war had a relatively high IQ. Overcrowding in
      the school catchment area was weakly related to death. Controlling for this
      factor did not alter the association between mental ability and mortality.
      CONCLUSION: Childhood mental ability is a significant factor among the variables
      that predict age at death.

PMID- 11290634
TI  - The UK accelerated immunisation programme and sudden unexpected death in infancy:
      case-control study.
AB  - OBJECTIVES: To investigate whether the accelerated immunisation programme in the
      United Kingdom is associated, after adjustment for potential confounding, with
      the sudden infant death syndrome. DESIGN: Population based case-control study,
      February 1993 to March 1996. Parental interviews were conducted for each death
      and for four controls matched for age, locality, and time of sleep. Immunisation
      status was taken from records held by the parents. SETTING: Five regions in
      England with a combined population of over 17 million. SUBJECTS: Immunisation
      details were available for 93% (303/325) of infants whose deaths were attributed
      to the sudden infant death syndrome (SIDS); 90% (65/72) of infants with explained
      sudden deaths; and 95% (1515/1588) of controls. RESULTS: After all potential
      confounding factors were controlled for, immunisation uptake was strongly
      associated with a lower risk of SIDS (odds ratio 0.45 (95% confidence interval
      0.24 to 0.85)). This difference became non-significant (0.67 (0.31 to 1.43))
      after further adjustment for other factors specific to the infant's sleeping
      environment. Similar proportions of SIDS deaths and reference sleeps
      (corresponding to the time of day during which the index baby had died) among the
      controls occurred within 48 hours of the last vaccination (5% (7/149) v 5%
      (41/822)) and within two weeks (21% (31/149) v 27% (224/822)). No longer term
      temporal association with immunisation was found (P=0.78). Of the SIDS infants
      who died within two weeks of vaccination, 16% (5/31) had signs and symptoms of
      illness that suggested that medical contact was required, compared with 26%
      (16/61) of the non-immunised SIDS infants of similar age. The findings for the
      infants who died suddenly and unexpectedly but of explained causes mirrored those
      for SIDS infants. CONCLUSIONS: Immunisation does not lead to sudden unexpected
      death in infancy, and the direction of the relation is towards protection rather
      than risk.

PMID- 11290635
TI  - Compliance, satisfaction, and quality of life of patients with colorectal cancer
      receiving home chemotherapy or outpatient treatment: a randomised controlled
      trial.
AB  - OBJECTIVE: To compare chemotherapy given at home with outpatient treatment in
      terms of colorectal cancer patients' safety, compliance, use of health services,
      quality of life, and satisfaction with treatment. DESIGN: Randomised controlled
      trial. SETTING: Large teaching hospital. PARTICIPANTS: 87 patients receiving
      adjuvant or palliative chemotherapy for colorectal cancer. INTERVENTIONS:
      Treatment with fluorouracil (with or without folinic acid or levamisole) at
      outpatient clinic or at home. MAIN OUTCOME MEASURES: Treatment toxicity;
      patients' compliance with treatment, quality of life, satisfaction with care, and
      use of health resources. RESULTS: 42 patients were treated at outpatient clinic
      and 45 at home. The two groups were balanced in terms of age, sex, site of
      cancer, and disease stage. Treatment related toxicity was similar in the two
      groups (difference 7% (95% confidence interval -12% to 26%)), but there were more
      voluntary withdrawals from treatment in the outpatient group than in the home
      group (14% v 2%, difference 12% (1% to 24%)). There were no differences between
      groups in terms of quality of life scores during and after treatment. Levels of
      patient satisfaction were higher in the home treatment group, specifically with
      regard to information received and nursing care. There were no significant
      differences in use of health services. CONCLUSIONS: Home chemotherapy seemed an
      acceptable and safe alternative to hospital treatment for patients with
      colorectal cancer that may improve compliance and satisfaction with treatment.

PMID- 11290636
TI  - Fatigue, alcohol, and serious road crashes in France: factorial study of national
      data.

PMID- 11290637
TI  - Relation between socioeconomic status and tumour stage in patients with breast,
      colorectal, ovarian, and lung cancer: results from four national, population
      based studies.

PMID- 11290638
TI  - Sex inequalities in ischaemic heart disease in general practice: cross sectional
      survey.
AB  - OBJECTIVE: To study differences in treatment for men and women with ischaemic
      heart disease by using standards defined in England's national service framework
      for coronary artery disease. DESIGN: Cross sectional survey using routinely
      collected data. SETTING: 18 practices in 18 primary care groups in Trent Region.
      SUBJECTS: 5891 men and women aged over 35 years with a diagnosis of ischaemic
      heart disease or prescription for nitrates recorded on computer. MAIN OUTCOME
      MEASURE: Difference in the proportion of men and women with ischaemic heart
      disease and taking lipid lowering treatment. RESULTS: Women were less likely than
      men to have a recording of body mass index (79% (2197/2783) v 82% (2552/3102),
      P=0.002), smoking (86% (2386) v 89% (2779), P<0.0001), and blood pressure (95%
      (2643) v 96% (2986), P=0.04). Women were also less likely to have a recording of
      fasting cholesterol concentration (35% (968) v 50% (1550), P<0.0001) but were
      more likely to be obese (25% (558/2197) v 20% (514/2552), P<0.0001) and have
      their most recently recorded blood pressure value over the recommended 140/85 mm
      Hg (60% (1598/2643) v 52% (1553/2986), P<0.0001). Although a higher proportion of
      women had a raised serum cholesterol concentration (77% (749/968) v 67%
      (1043/1550), P<0.0001), men were more likely to take aspirin (76% (2358) v 71%
      (1979), P<0.0001), have a recorded diagnosis of hyperlipidaemia (13% (418) v 10%
      (274), P<0.0001), and be prescribed lipid lowering drugs (31% (973) v 21% (596),
      P<0.0001). These differences remained despite adjustments for the practice where
      the patient is registered, age, smoking status, obesity, diabetes, and
      hypertension. CONCLUSION: The results suggest a systematic bias towards men
      compared with women in terms of secondary prevention of ischaemic heart disease.

PMID- 11290639
TI  - Randomised trial of personalised computer based information for patients with
      schizophrenia.
AB  - OBJECTIVES: To compare use, effect, and cost of personalised computer education
      with community psychiatric nurse education for patients with schizophrenia.
      DESIGN: Randomised trial of three interventions. Modelling of costs of
      alternatives. PARTICIPANTS: 112 patients with schizophrenia in contact with
      community services; 67 completed the intervention. INTERVENTIONS: Three
      interventions of five educational sessions: (a) computer intervention combining
      information from patient's medical record with general information about
      schizophrenia; (b) sessions with a community psychiatric nurse; (c) "combination"
      (first and last sessions with nurse and remainder with computer). MAIN OUTCOME
      MEASURES: Patients' attendance, opinions, change in knowledge, and psychological
      state; costs of interventions and patients' use of NHS community services;
      modelling of costs for these three, and alternative, interventions. RESULTS:
      Rates of completion of intervention did not differ significantly (71% for
      combination intervention, 61% for computer only, 46% for nurse only). Computer
      sessions were shorter than sessions with nurse (14 minutes v 60 minutes). More
      patients given nurse based education thought the information relevant. Of 20
      patients in combination group, 13 preferred the sessions with the nurse and seven
      preferred the computer. There were no significant differences between groups in
      psychological outcomes. Because of the need to transport patients to the computer
      for their sessions, there was no difference between interventions in costs, but
      computer sessions combined with other patient contacts would be substantially
      cheaper. CONCLUSIONS: The computer based patient education offered no advantage
      over sessions with a community psychiatric nurse. Investigation of computer use
      combined with other health service contacts would be worth while.

PMID- 11290640
TI  - Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease.

PMID- 11290641
TI  - Postherpetic neuralgia. Findings differ from earlier results.

PMID- 11290642
TI  - ABC of diseases of liver, pancreas, and biliary system: Transplantation of the
      liver and pancreas.

PMID- 11290644
TI  - External assessment of health care.

PMID- 11290643
TI  - Potential impact of the Human Rights Act on psychiatric practice: the best of
      British values?

PMID- 11290645
TI  - Postherpetic neuralgia. Why burden the pain clinic?

PMID- 11290646
TI  - Care of older people: Falls in late life and their consequences-implementing
      effective services.

PMID- 11290647
TI  - Postherpetic neuralgia. Treatment with amitriptyline is cheaper than with
      aciclovir.

PMID- 11290648
TI  - High dose methylprednisolone must be given for 24 or 48 hours after acute spinal
      cord injury.

PMID- 11290649
TI  - Non-combatants are often injured while clearing mines.

PMID- 11290651
TI  - Africa deserves better treatment from the West.

PMID- 11290652
TI  - Television programmes could market breast feeding.

PMID- 11290653
TI  - Osteoporosis is a risk factor, not a disease.

PMID- 11290654
TI  - Refugee doctors find it hard to get back into practice.

PMID- 11290655
TI  - Trial experience and recollection of consent.

PMID- 11290656
TI  - Using patient identifiable data without consent. Obtaining individual consent may
      hinder studies.

PMID- 11290657
TI  - Using patient identifiable data without consent. Argument for consent may
      invalidate research and stigmatise some patients.

PMID- 11290659
TI  - Editor's pick. Major changes in clinical medical education.

PMID- 11290660
TI  - Point-Counterpoint: is it ethical to give drugs to people with dementia? Yes: It
      is ethical if it is in their best interests.

PMID- 11290661
TI  - Point-Counterpoint: is it ethical to give drugs covertly to people with dementia?
      No: Covert medication is paternalistic.

PMID- 11290662
TI  - Spiral computed tomography screening: study begins to determine its efficacy in
      lung cancer prevention.

PMID- 11290663
TI  - An innovative guide to outpatient medicine: Our new monthly series aims to help
      physicians manage outpatient conditions.

PMID- 11290664
TI  - Do drug company promotions influence physician behavior?

PMID- 11290665
TI  - Ensuring safe nurse-to-patient ratios: Safe Staffing Bill mandates ratios based
      on patients' needs rather than budgets.

PMID- 11290667
TI  - United States takes precautions against BSE.

PMID- 11290668
TI  - Hospital bans free drug samples.

PMID- 11290669
TI  - Risk of ulcer soars with combination of arthritis drugs.

PMID- 11290670
TI  - A boy with undescended testes.

PMID- 11290672
TI  - Waist-to-hip ratio versus BMI as predictors of cardiac risk in obese adult women.

PMID- 11290673
TI  - Misdiagnosis of brown recluse spider bite.

PMID- 11290675
TI  - Toward a new definition of chronic fatigue syndrome.

PMID- 11290677
TI  - Where have all the preceptors gone? Erosion of the volunteer clinical faculty.

PMID- 11290676
TI  - Volunteer physician faculty and the changing face of medicine.
AB  - OBJECTIVE: To determine the extent to which current changes in the American
      health care system might adversely effect the willingness of community physicians
      to volunteer to teach medical students. DESIGN: Surveys in the form of 2 mailings
      were sent to 466 physicians in the Pacific Northwest who volunteer to teach first
      and second-year medical students. The physicians were categorized into medical
      specialty or primary care, urban or rural location, and type of practice.
      PARTICIPANTS: A total of 333 physicians completed the surveys on which responses
      were analyzed. RESULTS: Respondents noted that clinical and nonclinical workloads
      had increased (n=211 [63%] and n=276 [83%], respectively) in the past 5 years.
      One hundred eighty-six respondents (56%) said that they had less time for
      teaching medical students. Forty-five physicians (14%) indicated that they had
      discontinued their volunteer teaching activities altogether. During the past 5
      years, solo practitioners had the lowest dropout rate (7% [4/57]), and physicians
      at health maintenance organizations had the highest (23% [7/30]). Primary care
      physicians were more likely to indicate that they had decreased time for each
      patient encounter (P=0.006). CONCLUSIONS: Increasing nonclinical workload demands
      and higher patient loads are a substantial threat to the recruitment and
      retention of volunteer faculty. In particular, the involvement of urban, HMO, and
      primary care physicians may decrease disproportionately in the future.

PMID- 11290678
TI  - Collusion in doctor-patient communication about imminent death: an ethnographic
      study.
AB  - OBJECTIVE: To discover and explore the factors that result in the "false optimism
      about recovery" observed in patients with small cell lung cancer. DESIGN: A
      qualitative observational (ethnographic) study in 2 stages over 4 years. SETTING:
      Lung diseases ward and outpatient clinic in a university hospital in the
      Netherlands. PARTICIPANTS: 35 patients with small cell lung cancer. RESULTS:
      False optimism about recovery usually developed during the first course of
      chemotherapy and was most prevalent when the cancer could no longer be seen on x
      ray films. This optimism tended to vanish when the tumor recurred, but it could
      develop again, though to a lesser extent, during further courses of chemotherapy.
      Patients gradually found out the facts about their poor prognosis, partly by
      their physical deterioration and partly through contact with fellow patients in a
      more advanced stage of the illness who were dying. False optimism about recovery
      was the result of an association between physicians' activism and patients'
      adherence to the treatment calendar and to the "recovery plot," which allowed
      them to avoid acknowledging explicitly what they should and could know. The
      physician did and did not want to pronounce a "death sentence," and the patient
      did and did not want to hear it. CONCLUSION: Solutions to the problem of
      collusion between physician and patient require an active, patient-oriented
      approach by the physician. Perhaps solutions have to be found outside the
      physician-patient relationship itself--for example, by involving "treatment
      brokers."

PMID- 11290679
TI  - Physicians, patients, and prognosis.

PMID- 11290681
TI  - Can a D-dimer assay, alone or combined with structured clinical risk assessment,
      rule out deep venous thrombosis in symptomatic patients?

PMID- 11290684
TI  - Coronary artery disease: Part 1. Epidemiology and diagnosis.
AB  - Coronary artery disease (CAD) is the leading cause of death in Americans,
      accounting for about 500,000 deaths every year. The annual incidence of
      myocardial infarction (MI) is about 1.5 million. As many as 2 million middle-aged
      men may have silent myocardial ischemia. (1)

PMID- 11290685
TI  - Which guidelines can we trust?: Assessing strength of evidence behind
      recommendations for clinical practice.

PMID- 11290686
TI  - Knee instability: isolated and complex.

PMID- 11290687
TI  - Complementary and alternative medicine for children: does it work?

PMID- 11290688
TI  - Helping pregnant smokers quit: meeting the challenge in the next decade.

PMID- 11290691
TI  - Adjuvant therapy for breast cancer: who should get what?

PMID- 11290689
TI  - Should people stretch before exercise?

PMID- 11290692
TI  - Adjuvant therapies for breast cancer.

PMID- 11290695
TI  - Kindness and the end of life.

PMID- 11290693
TI  - Dental damage, sequelae, and prevention.

PMID- 11290697
TI  - A patient remembered.

PMID- 11290699
TI  - Differential evolution of eastern equine encephalitis virus populations in
      response to host cell type.
AB  - Arthropod-borne viruses (arboviruses) cycle between hosts in two widely separated
      taxonomic groups, vertebrate amplifying hosts and invertebrate vectors, both of
      which may separately or in concert shape the course of arbovirus evolution. To
      elucidate the selective pressures associated with virus replication within each
      portion of this two-host life cycle, the effects of host type on the growth
      characteristics of the New World alphavirus, eastern equine encephalitis (EEE)
      virus, were investigated. Multiple lineages of an ancestral EEE virus stock were
      repeatedly transferred through either mosquito or avian cells or in alternating
      passages between these two cell types. When assayed in both cell types, derived
      single host lineages exhibited significant differences in infectivity, growth
      pattern, plaque morphology, and total virus yield, demonstrating that this virus
      is capable of host-specific evolution. Virus lineages grown in alternation
      between the two cell types expressed intermediate phenotypes consistent with dual
      adaptation to both cellular environments. Both insect-adapted and alternated
      lineages greatly increased in their ability to infect insect cells. These results
      indicate that different selective pressures exist for virus replication within
      each portion of the two-host life cycle, and that alternation of hosts selects
      for virus populations well adapted for replication in both host systems.

PMID- 11290700
TI  - Localized remodeling of the Escherichia coli chromosome: the patchwork of
      segments refractory and tolerant to inversion near the replication terminus.
AB  - The behavior of chromosomal inversions in Escherichia coli depends upon the
      region they affect. Regions flanking the replication terminus have been termed
      nondivisible zones (NDZ) because inversions ending in the region were either
      deleterious or not feasible. This regional phenomenon is further analyzed here.
      Thirty segments distributed between 23 and 29 min on the chromosome map have been
      submitted to an inversion test. Twenty-five segments either became deleterious
      when inverted or were noninvertible, but five segments tolerated inversion. The
      involvement of polar replication pause sites in this distribution was
      investigated. The results suggest that the Tus/pause site system may forbid some
      inversion events, but that other constraints to inversion, unrelated to this
      system, exist. Our current model for deleterious inversions is that the segments
      involved carry polar sequences acting in concert with other polar sequences
      located outside the segments. The observed patchwork of refractory and tolerant
      segments supports the existence of several NDZs in the 23- to 29-min region.
      Microscopic observations revealed that deleterious inversions are associated with
      high frequencies of abnormal nucleoid structure and distribution. Combined with
      other information, the data suggest that NDZs participate in the organization of
      the terminal domain of the nucleoid.

PMID- 11290701
TI  - Overexpression of translation elongation factor 1A affects the organization and
      function of the actin cytoskeleton in yeast.
AB  - The translation elongation factor 1 complex (eEF1) plays a central role in
      protein synthesis, delivering aminoacyl-tRNAs to the elongating ribosome. The
      eEF1A subunit, a classic G-protein, also performs roles aside from protein
      synthesis. The overexpression of either eEF1A or eEF1B alpha, the catalytic
      subunit of the guanine nucleotide exchange factor, in Saccharomyces cerevisiae
      results in effects on cell growth. Here we demonstrate that overexpression of
      either factor does not affect the levels of the other subunit or the rate or
      accuracy of protein synthesis. Instead, the major effects in vivo appear to be at
      the level of cell morphology and budding. eEF1A overexpression results in dosage
      dependent reduced budding and altered actin distribution and cellular morphology.
      In addition, the effects of excess eEF1A in actin mutant strains show synthetic
      growth defects, establishing a genetic connection between the two proteins. As
      the ability of eEF1A to bind and bundle actin is conserved in yeast, these
      results link the established ability of eEF1A to bind and bundle actin in vitro
      with nontranslational roles for the protein in vivo.

PMID- 11290702
TI  - A novel functional domain of Cdc15 kinase is required for its interaction with
      Tem1 GTPase in Saccharomyces cerevisiae.
AB  - Exit from mitosis requires the inactivation of cyclin-dependent kinase (CDK)
      activity. In the budding yeast Saccharomyces cerevisiae, a number of gene
      products have been identified as components of the signal transduction network
      regulating inactivation of CDK (called the MEN, for the mitotic exit network).
      Cdc15, one of such components of the MEN, is an essential protein kinase. By the
      two-hybrid screening, we identified Cdc15 as a binding protein of Tem1 GTPase,
      another essential regulator of the MEN. Coprecipitation experiments revealed that
      Tem1 binds to Cdc15 in vivo. By deletion analysis, we found that the Tem1-binding
      domain resides near the conserved kinase domain of Cdc15. The cdc15-LF mutation,
      which was introduced into the Tem1-binding domain, reduced the interaction with
      Cdc15 and Tem1 and caused temperature-sensitive growth. The kinase activity of
      Cdc15 was not so much affected by the cdc15-LF mutation. However, Cdc15-LF failed
      to localize to the SPB at the restrictive temperature. Our data show that the
      interaction with Tem1 is important for the function of Cdc15 and that Cdc15 and
      Tem1 function in a complex to direct the exit from mitosis.

PMID- 11290704
TI  - Isolation and characterization of WHI3, a size-control gene of Saccharomyces
      cerevisiae.
AB  - WHI3 is a gene affecting size control and cell cycle in the yeast Saccharomyces
      cerevisiae. The whi3 mutant has small cells, while extra doses of WHI3 produce
      large cells, and a large excess of WHI3 produces a lethal arrest in G1 phase.
      WHI3 seems to be a dose-dependent inhibitor of Start. Whi3 and its partially
      redundant homolog Whi4 have an RNA-binding domain, and mutagenesis experiments
      indicate that this RNA-binding domain is essential for Whi3 function. CLN3-1 whi3
      cells are extremely small, nearly sterile, and largely nonresponsive to mating
      factor. Fertility is restored by deletion of CLN2, suggesting that whi3 cells may
      have abnormally high levels of CLN2 function.

PMID- 11290703
TI  - Functional contacts with a range of splicing proteins suggest a central role for
      Brr2p in the dynamic control of the order of events in spliceosomes of
      Saccharomyces cerevisiae.
AB  - Mapping of functional protein interactions will help in understanding
      conformational rearrangements that occur within large complexes like
      spliceosomes. Because the U5 snRNP plays a central role in pre-mRNA splicing, we
      undertook exhaustive two-hybrid screening with Brr2p, Prp8p, and other U5 snRNP
      associated proteins. DExH-box protein Brr2p interacted specifically with five
      splicing factors: Prp8p, DEAH-box protein Prp16p, U1 snRNP protein Snp1p, second
      step factor Slu7p, and U4/U6.U5 tri-snRNP protein Snu66p, which is required for
      splicing at low temperatures. Co-immunoprecipitation experiments confirmed direct
      or indirect interactions of Prp16p, Prp8p, Snu66p, and Snp1p with Brr2p and led
      us to propose that Brr2p mediates the recruitment of Prp16p to the spliceosome.
      We provide evidence that the prp8-1 allele disrupts an interaction with Brr2p,
      and we propose that Prp8p modulates U4/U6 snRNA duplex unwinding through another
      interaction with Brr2p. The interactions of Brr2p with a wide range of proteins
      suggest a particular function for the C-terminal half, bringing forward the
      hypothesis that, apart from U4/U6 duplex unwinding, Brr2p promotes other RNA
      rearrangements, acting synergistically with other spliceosomal proteins,
      including the structurally related Prp2p and Prp16p. Overall, these protein
      interaction studies shed light on how splicing factors regulate the order of
      events in the large spliceosome complex.

PMID- 11290705
TI  - Efficient incorporation of large (>2 kb) heterologies into heteroduplex DNA:
      Pms1/Msh2-dependent and -independent large loop mismatch repair in Saccharomyces
      cerevisiae.
AB  - DNA double-strand break (DSB) repair in yeast is effected primarily by gene
      conversion. Conversion can conceivably result from gap repair or from mismatch
      repair of heteroduplex DNA (hDNA) in recombination intermediates. Mismatch repair
      is normally very efficient, but unrepaired mismatches segregate in the next cell
      division, producing sectored colonies. Conversion of small heterologies (single
      base differences or insertions <15 bp) in meiosis and mitosis involves mismatch
      repair of hDNA. The repair of larger loop mismatches in plasmid substrates or
      arising by replication slippage is inefficient and/or independent of Pms1p/Msh2p
      dependent mismatch repair. However, large insertions convert readily (without
      sectoring) during meiotic recombination, raising the question of whether large
      insertions convert by repair of large loop mismatches or by gap repair. We show
      that insertions of 2.2 and 2.6 kbp convert efficiently during DSB-induced mitotic
      recombination, primarily by Msh2p- and Pms1p-dependent repair of large loop
      mismatches. These results support models in which Rad51p readily incorporates
      large heterologies into hDNA. We also show that large heterologies convert more
      frequently than small heterologies located the same distance from an initiating
      DSB and propose that this reflects Msh2-independent large loop-specific mismatch
      repair biased toward loop loss.

PMID- 11290706
TI  - The spindle checkpoint of the yeast Saccharomyces cerevisiae requires kinetochore
      function and maps to the CBF3 domain.
AB  - We have measured the activity of the spindle checkpoint in null mutants lacking
      kinetochore activity in the yeast Saccharomyces cerevisiae. We constructed
      deletion mutants for nonessential genes by one-step gene replacements. We
      constructed heterozygous deletions of one copy of essential genes in diploid
      cells and purified spores containing the deletion allele. In addition, we made
      gene fusions for three essential genes to target the encoded proteins for
      proteolysis (degron alleles). We determined that Ndc10p, Ctf13p, and Cep3p are
      required for checkpoint activity. In contrast, cells lacking Cbf1p, Ctf19p,
      Mcm21p, Slk19p, Cse4p, Mif2p, Mck1p, and Kar3p are checkpoint proficient. We
      conclude that the kinetochore plays a critical role in checkpoint signaling in S.
      cerevisiae. Spindle checkpoint activity maps to a discreet domain within the
      kinetochore and depends on the CBF3 protein complex.

PMID- 11290707
TI  - The DNA binding protein Rfg1 is a repressor of filamentation in Candida albicans.
AB  - We have identified a repressor of hyphal growth in the pathogenic yeast Candida
      albicans. The gene was originally cloned in an attempt to characterize the
      homologue of the Saccharomyces cerevisiae Rox1, a repressor of hypoxic genes.
      Rox1 is an HMG-domain, DNA binding protein with a repression domain that recruits
      the Tup1/Ssn6 general repression complex to achieve repression. The C. albicans
      clone also encoded an HMG protein that was capable of repression of a hypoxic
      gene in a S. cerevisiae rox1 deletion strain. Gel retardation experiments using
      the purified HMG domain of this protein demonstrated that it was capable of
      binding specifically to a S. cerevisiae hypoxic operator DNA sequence. These data
      seemed to indicate that this gene encoded a hypoxic repressor. However,
      surprisingly, when a homozygous deletion was generated in C. albicans, the cells
      became constitutive for hyphal growth. This phenotype was rescued by the
      reintroduction of the wild-type gene on a plasmid, proving that the hyphal growth
      phenotype was due to the deletion and not a secondary mutation. Furthermore,
      oxygen repression of the hypoxic HEM13 gene was not affected by the deletion nor
      was this putative ROX1 gene regulated positively by oxygen as is the case for the
      S. cerevisiae gene. All these data indicate that this gene, now designated RFG1
      for Repressor of Filamentous Growth, is a repressor of genes required for hyphal
      growth and not a hypoxic repressor.

PMID- 11290708
TI  - Fission yeast Mog1p homologue, which interacts with the small GTPase Ran, is
      required for mitosis-to-interphase transition and poly(A)(+) RNA metabolism.
AB  - We have cloned and characterized the Schizosaccharomyces pombe gene mog1(+),
      which encodes a protein with homology to the Saccharomyces cerevisiae Mog1p
      participating in the Ran-GTPase system. The S. pombe Mog1p is predominantly
      localized in the nucleus. In contrast to the S. cerevisiae MOG1 gene, the S.
      pombe mog1(+) gene is essential for cell viability. mog1(+) is required for the
      mitosis-to-interphase transition, as the mog1-1 mutant arrests at restrictive
      temperatures as septated, binucleated cells with highly condensed chromosomes and
      an aberrant nuclear envelope. FACS analysis showed that these cells do not
      undergo a subsequent round of DNA replication. Surprisingly, also unlike the
      Delta mog1 mutation in S. cerevisiae, the mog1-1 mutation causes nucleolar
      accumulation of poly(A)(+) RNA at the restrictive temperature in S. pombe, but
      the signals do not overlap with the fibrillarin-rich region of the nucleolus.
      Thus, we found that mog1(+) is required for the mitosis-to-interphase transition
      and a class of RNA metabolism. In our attempt to identify suppressors of mog1-1,
      we isolated the spi1(+) gene, which encodes the fission yeast homologue of Ran.
      We found that overexpression of Spi1p rescues the S. pombe Delta mog1 cells from
      death. On the basis of these results, we conclude that mog1(+) is involved in the
      Ran-GTPase system.

PMID- 11290709
TI  - A potential phosphorylation site for an A-type kinase in the Efg1 regulator
      protein contributes to hyphal morphogenesis of Candida albicans.
AB  - Efg1p in the human fungal pathogen Candida albicans is a member of the conserved
      APSES class of proteins regulating morphogenetic processes in fungi. We have
      analyzed the importance for hyphal morphogenesis of a putative phosphorylation
      site for protein kinase A (PKA), threonine-206, within an Efg1p domain highly
      conserved among APSES proteins. Alanine substitution of T206, but not of the
      adjacent T207 and T208 residues, led to a block of hypha formation on solid and
      in liquid media, while a T206E exchange caused hyperfilamentation. The extent of
      the morphogenetic defect caused by the T206A mutation depended on hypha-induction
      conditions. Extragenous suppression of mutations in signaling components,
      including tpk2 and cek1 mutations, was achieved by wild-type- and T206E-, but not
      by the T206A-variant-encoding allele of EFG1. All muteins tested were produced at
      equal levels and at high production levels supported pseudohyphal formation. The
      results are consistent with a role of Efg1p as a central downstream component of
      a PKA-signaling pathway including Tpk2p or other PKA isoforms. Threonine-206 of
      Efg1p is essential as a putative phosphorylation target to promote hyphal
      induction by a subset of environmental cues.

PMID- 11290711
TI  - Novel role for a Saccharomyces cerevisiae nucleoporin, Nup170p, in chromosome
      segregation.
AB  - We determined that a mutation in the nucleoporin gene NUP170 leads to defects in
      chromosome transmission fidelity (ctf) and kinetochore integrity in Saccharomyces
      cerevisiae. A ctf mutant strain, termed s141, shows a transcription readthrough
      phenotype and stabilizes a dicentric chromosome fragment in two assays for
      kinetochore integrity. Previously, these assays led to the identification of two
      essential kinetochore components, Ctf13p and Ctf14p. Thus, s141 represents
      another ctf mutant involved in the maintenance of kinetochore integrity. We
      cloned and mapped the gene complementing the ctf mutation of s141 and showed that
      it is identical to the S. cerevisiae NUP170 gene. A deletion strain of NUP170
      (nup170 Delta::HIS3) has a Ctf(-) phenotype similar to the s141 mutant (nup170
      141) and also exhibits a kinetochore integrity defect. We identified a second
      nucleoporin, NUP157, a homologue of NUP170, as a suppressor of the Ctf(-)
      phenotype of nup170-141 and nup170 Delta::HIS3 strains. However, a deletion of
      NUP157 or several other nucleoporins did not affect chromosome segregation. Our
      data suggest that NUP170 encodes a specialized nucleoporin with a unique role in
      chromosome segregation and possibly kinetochore function.

PMID- 11290710
TI  - The short life span of Saccharomyces cerevisiae sgs1 and srs2 mutants is a
      composite of normal aging processes and mitotic arrest due to defective
      recombination.
AB  - Evidence from many organisms indicates that the conserved RecQ helicases function
      in the maintenance of genomic stability. Mutation of SGS1 and WRN, which encode
      RecQ homologues in budding yeast and humans, respectively, results in phenotypes
      characteristic of premature aging. Mutation of SRS2, another DNA helicase, causes
      synthetic slow growth in an sgs1 background. In this work, we demonstrate that
      srs2 mutants have a shortened life span similar to sgs1 mutants. Further
      dissection of the sgs1 and srs2 survival curves reveals two distinct phenomena. A
      majority of sgs1 and srs2 cells stops dividing stochastically as large-budded
      cells. This mitotic cell cycle arrest is age independent and requires the RAD9
      dependent DNA damage checkpoint. Late-generation sgs1 and srs2 cells senesce due
      to apparent premature aging, most likely involving the accumulation of
      extrachromosomal rDNA circles. Double sgs1 srs2 mutants are viable but have a
      high stochastic rate of terminal G2/M arrest. This arrest can be suppressed by
      mutations in RAD51, RAD52, and RAD57, suggesting that the cell cycle defect in
      sgs1 srs2 mutants results from inappropriate homologous recombination. Finally,
      mutation of RAD1 or RAD50 exacerbates the growth defect of sgs1 srs2 cells,
      indicating that sgs1 srs2 mutants may utilize single-strand annealing as an
      alternative repair pathway.

PMID- 11290712
TI  - Characterization of agglutinin-like sequence genes from non-albicans Candida and
      phylogenetic analysis of the ALS family.
AB  - The ALS (agglutinin-like sequence) gene family of Candida albicans encodes cell
      surface glycoproteins implicated in adhesion of the organism to host surfaces.
      Southern blot analysis with ALS-specific probes suggested the presence of ALS
      gene families in C. dubliniensis and C. tropicalis; three partial ALS genes were
      isolated from each organism. Northern blot analysis demonstrated that mechanisms
      governing expression of ALS genes in C. albicans and C. dubliniensis are
      different. Western blots with an anti-Als serum showed that cross-reactive
      proteins are linked by beta 1,6-glucan in the cell wall of each non-albicans
      Candida, suggesting similar cell wall architecture and conserved processing of
      Als proteins in these organisms. Although an ALS family is present in each
      organism, phylogenetic analysis of the C. albicans, C. dubliniensis, and C.
      tropicalis ALS genes indicated that, within each species, sequence
      diversification is extensive and unique ALS sequences have arisen. Phylogenetic
      analysis of the ALS and SAP (secreted aspartyl proteinase) families show that the
      ALS family is younger than the SAP family. ALS genes in C. albicans, C.
      dubliniensis, and C. tropicalis tend to be located on chromosomes that also
      encode genes from the SAP family, yet the two families have unexpectedly
      different evolutionary histories. Homologous recombination between the tandem
      repeat sequences present in ALS genes could explain the different histories for
      co-localized genes in a predominantly clonal organism like C. albicans.

PMID- 11290713
TI  - Cis-elements governing trinucleotide repeat instability in Saccharomyces
      cerevisiae.
AB  - Trinucleotide repeat (TNR) instability in humans is governed by unique cis
      elements. One element is a threshold, or minimal repeat length, conferring
      frequent mutations. Since thresholds have not been directly demonstrated in model
      systems, their molecular nature remains uncertain. Another element is sequence
      specificity. Unstable TNR sequences are almost always CNG, whose hairpin-forming
      ability is thought to promote instability by inhibiting DNA repair. To understand
      these cis-elements further, TNR expansions and contractions were monitored by
      yeast genetic assays. A threshold of approximately 15--17 repeats was observed
      for CTG expansions and contractions, indicating that thresholds function in
      organisms besides humans. Mutants lacking the flap endonuclease Rad27p showed
      little change in the expansion threshold, suggesting that this element is not
      altered by the presence or absence of flap processing. CNG or GNC sequences
      yielded frequent mutations, whereas A-T rich sequences were substantially more
      stable. This sequence analysis further supports a hairpin-mediated mechanism of
      TNR instability. Expansions and contractions occurred at comparable rates for CTG
      tract lengths between 15 and 25 repeats, indicating that expansions can comprise
      a significant fraction of mutations in yeast. These results indicate that several
      unique cis-elements of human TNR instability are functional in yeast.

PMID- 11290714
TI  - Escape from repeat-induced point mutation of a gene-sized duplication in
      Neurospora crassa crosses that are heterozygous for a larger chromosome segment
      duplication.
AB  - In Neurospora crassa the ability of an ectopic gene-sized duplication to induce
      repeat-induced point mutation (RIP) in its target gene was suppressed in crosses
      that were heterozygous for another larger chromosome segment duplication.
      Specifically, the frequency of RIP in the erg-3 gene due to a 1.3-kb duplication
      was reduced if the chromosome segment duplications Dp(IIIR > [I;II]) AR17, Dp(VIR
      > IIIR) OY329, or Dp(IVR > VII) S1229 were present in either the same or the
      other parental nucleus of the premeiotic dikaryon. We suggest that the larger
      duplications act as sinks to titrate the RIP machinery away from the smaller
      duplication. In contrast, RIP efficiency was relatively unaffected in comparably
      unproductive interspecies crosses with N. intermedia and N. tetrasperma. These
      findings offer a novel explanation for the observed persistence of the
      transposable element Tad in only a subset of Neurospora strains.

PMID- 11290715
TI  - The transition from conjugal development to the first vegetative cell division is
      dependent on RAD51 expression in the ciliate Tetrahymena thermophila.
AB  - Rad51p, the eukaryotic homolog of the prokaryotic recA protein, catalyzes strand
      exchange between single- and double-stranded DNA and is involved in both genetic
      recombination and double-strand break repair in the ciliate Tetrahymena
      thermophila. We have previously shown that disruption of the Tetrahymena RAD51
      somatic macronuclear locus leads to defective germline micronuclear division and
      that conjugation of two somatic rad51 null strains results in an early meiotic
      arrest. We have constructed Tetrahymena strains that are capable of RAD51
      expression from their parental macronuclei and are homozygous, rad51 nulls in
      their germline micronuclei. These rad51 null heterokaryons complete all of the
      early and middle stages of conjugation, including meiosis, haploid nuclear
      exchange, zygotic fusion, and the programmed chromosome fragmentations, sequence
      eliminations, and rDNA amplification that occur during macronuclear development.
      However, the rad51 null progeny fail to initiate the first vegetative cell
      division following conjugal development. Coincident with the developmental arrest
      is a disproportionate amplification of rDNA, despite the maintenance of normal
      total DNA content in the developing macronuclei. Fusion of arrested rad51 null
      exconjugants to wild-type cells is sufficient to overcome the arrest. Cells
      rescued by cytoplasmic fusion continue to divide, eventually recapitulating the
      micronuclear mitotic defects described previously for rad51 somatic nulls.

PMID- 11290716
TI  - Genes affecting the activity of nicotinic receptors involved in Caenorhabditis
      elegans egg-laying behavior.
AB  - Egg-laying behavior in Caenorhabditis elegans is regulated by multiple
      neurotransmitters, including acetylcholine and serotonin. Agonists of nicotinic
      acetylcholine receptors such as nicotine and levamisole stimulate egg laying;
      however, the genetic and molecular basis for cholinergic neurotransmission in the
      egg-laying circuitry is not well understood. Here we describe the egg-laying
      phenotypes of eight levamisole resistance genes, which affect the activity of
      levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes,
      including the nicotinic receptor subunit genes unc-29, unc-38, and lev-1, were
      essential for the stimulation of egg laying by levamisole, though they had only
      subtle effects on egg-laying behavior in the absence of drug. Thus, these genes
      appear to encode components of a nicotinic receptor that can promote egg laying
      but is not necessary for egg-laying muscle contraction. Since the levamisole
      receptor mutants responded to other cholinergic drugs, other acetylcholine
      receptors are likely to function in parallel with the levamisole-sensitive
      receptors to mediate cholinergic neurotransmission in the egg-laying circuitry.
      In addition, since expression of functional unc-29 in muscle cells restored
      levamisole sensitivity under some but not all conditions, both neuronal and
      muscle cell UNC-29 receptors are likely to contribute to the regulation of egg
      laying behavior. Mutations in one levamisole receptor gene, unc-38, also
      conferred both hypersensitivity and reduced peak response to serotonin; thus
      nicotinic receptors may play a role in regulating serotonin response pathways in
      the egg-laying neuromusculature.

PMID- 11290717
TI  - Mutations affecting nerve attachment of Caenorhabditis elegans.
AB  - Using a pan-neuronal GFP marker, a morphological screen was performed to detect
      Caenorhabditis elegans larval lethal mutants with severely disorganized major
      nerve cords. We recovered and characterized 21 mutants that displayed
      displacement or detachment of the ventral nerve cord from the body wall (Ven:
      ventral cord abnormal). Six mutations defined three novel genetic loci: ven-1,
      ven-2, and ven-3. Fifteen mutations proved to be alleles of previously identified
      muscle attachment/positioning genes, mup-4, mua-1, mua-5, and mua-6. All the
      mutants also displayed muscle attachment/positioning defects characteristic of
      mua/mup mutants. The pan-neuronal GFP marker also revealed that mutants of other
      mua/mup loci, such as mup-1, mup-2, and mua-2, exhibited the Ven defect. The
      hypodermis, the excretory canal, and the gonad were morphologically abnormal in
      some of the mutants. The pleiotropic nature of the defects indicates that ven and
      mua/mup genes are required generally for the maintenance of attachment of tissues
      to the body wall in C. elegans.

PMID- 11290718
TI  - Identification of chromosome inheritance modifiers in Drosophila melanogaster.
AB  - Faithful chromosome inheritance is a fundamental biological activity and errors
      contribute to birth defects and cancer progression. We have performed a P-element
      screen in Drosophila melanogaster with the aim of identifying novel candidate
      genes involved in inheritance. We used a "sensitized" minichromosome substrate
      (J21A) to screen approximately 3,000 new P-element lines for dominant effects on
      chromosome inheritance and recovered 78 Sensitized chromosome inheritance
      modifiers (Scim). Of these, 69 decreased minichromosome inheritance while 9
      increased minichromosome inheritance. Fourteen mutations are lethal or semilethal
      when homozygous and all exhibit dramatic mitotic defects. Inverse PCR combined
      with genomic analyses identified P insertions within or close to genes with
      previously described inheritance functions, including wings apart-like (wapl),
      centrosomin (cnn), and pavarotti (pav). Further, lethal insertions in replication
      factor complex 4 (rfc4) and GTPase-activating protein 1 (Gap1) exhibit specific
      mitotic chromosome defects, discovering previously unknown roles for these
      proteins in chromosome inheritance. The majority of the lines represent mutations
      in previously uncharacterized loci, many of which have human homologs, and we
      anticipate that this collection will provide a rich source of mutations in new
      genes required for chromosome inheritance in metazoans.

PMID- 11290720
TI  - Clinal variation for amino acid polymorphisms at the Pgm locus in Drosophila
      melanogaster.
AB  - Clinal variation is common for enzymes in the glycolytic pathway for Drosophila
      melanogaster and is generally accepted as an adaptive response to different
      climates. Although the enzyme phosphoglucomutase (PGM) possesses several allozyme
      polymorphisms, it is unique in that it had been reported to show no clinal
      variation. Our recent DNA sequence investigation of Pgm found extensive cryptic
      amino acid polymorphism segregating with the allozyme alleles. In this study, we
      characterize the geographic variation of Pgm amino acid polymorphisms at the
      nucleotide level along a latitudinal cline in the eastern United States. A survey
      of 15 SNPs across the Pgm gene finds significant clinal differentiation for the
      allozyme polymorphisms as well as for many of the cryptic amino acid
      polymorphisms. A test of independence shows that pervasive linkage disequilibrium
      across this gene region can explain many of the amino acid clines. A single Pgm
      haplotype defined by two amino acid polymorphisms shows the strongest correlation
      with latitude and the steepest change in allele frequency across the cline. We
      propose that clinal selection at Pgm may in part explain the extensive amino acid
      polymorphism at this locus and is consistent with a multilocus response to
      selection in the glycolytic pathway.

PMID- 11290721
TI  - The mutant phenotype associated with P-element alleles of the vestigial locus in
      Drosophila melanogaster may be caused by a readthrough transcript initiated at
      the P-element promoter.
AB  - We report here the isolation of a new P-element-induced allele of the vestigial
      locus vg(2a33), the molecular characterization of which allows us to propose a
      unifying explanation of the phenotypes of the large number of vestigial P-element
      alleles that now exists. The first P-element allele of vestigial to be isolated
      was vg(21), which results in a very weak mutant wing phenotype that is suppressed
      in the P cytotype. By destabilizing vg(2a33) in a dysgenic cross, we isolated the
      vg(2a33) allele, which exhibits a moderate mutant wing phenotype and is not
      suppressed by the P cytotype. The new allele is characterized by a 46-bp deletion
      that removes the 3'-proximal copy of the 11-bp internal repeat from the P element
      of vg(21). To understand how this subtle difference between the two alleles leads
      to a rather pronounced difference in their phenotypes, we mapped both the vg and
      P-element transcription units present in wild type and mutants. Using both 5'
      RACE and S1 protection, we found that P-element transcription is initiated 19 bp
      farther upstream than previously thought. Using primer extension, the start of vg
      transcription was determined to lie 435 bp upstream of the longest cDNA recovered
      to date and upstream of the P-element insertion site. Our discovery that the P
      element is situated within the first vg exon has prompted a reassessment of the
      large body of genetic data on a series of alleles derived from vg(21). Our
      current hypothesis to explain the degree of variation in the mutant phenotypes
      and their response to the P repressor invokes a critical RNA secondary structure
      in the vg transcript, the formation of which is hindered by a readthrough
      transcript initiated at the P-element promoter.

PMID- 11290719
TI  - Transgenic analysis of the Smad family of TGF-beta signal transducers in
      Drosophila melanogaster suggests new roles and new interactions between family
      members.
AB  - Smad signal transducers are required for transforming growth factor-beta-mediated
      developmental events in many organisms including humans. However, the roles of
      individual human Smad genes (hSmads) in development are largely unknown. Our
      hypothesis is that an hSmad performs developmental roles analogous to those of
      the most similar Drosophila Smad gene (dSmad). We expressed six hSmad and four
      dSmad transgenes in Drosophila melanogaster using the Gal4/UAS system and
      compared their phenotypes. Phylogenetically related human and Drosophila Smads
      induced similar phenotypes supporting the hypothesis. In contrast, two nearly
      identical hSmads generated distinct phenotypes. When expressed in wing imaginal
      disks, hSmad2 induced oversize wings while hSmad3 induced cell death. This
      observation suggests that a very small number of amino acid differences, between
      Smads in the same species, confer distinct developmental roles. Our observations
      also suggest new roles for the dSmads, Med and Dad, in dActivin signaling and
      potential interactions between these family members. Overall, the study
      demonstrates that transgenic methods in Drosophila can provide new information
      about non-Drosophila members of developmentally important multigene families.

PMID- 11290722
TI  - Statistical approaches to paternity analysis in natural populations and
      applications to the North Atlantic humpback whale.
AB  - We present a new method for paternity analysis in natural populations that is
      based on genotypic data that can take the sampling fraction of putative parents
      into account. The method allows paternity assignment to be performed in a
      decision theoretic framework. Simulations are performed to evaluate the utility
      and robustness of the method and to assess how many loci are necessary for
      reliable paternity inference. In addition we present a method for testing
      hypotheses regarding relative reproductive success of different ecologically or
      behaviorally defined groups as well as a new method for estimating the current
      population size of males from genotypic data. This method is an extension of the
      fractional paternity method to the case where only a proportion of all putative
      fathers have been sampled. It can also be applied to provide abundance estimates
      of the number of breeding males from genetic data. Throughout, the methods were
      applied to genotypic data collected from North Atlantic humpback whales
      (Megaptera novaeangliae) to test if the males that appear dominant during the
      mating season have a higher reproductive success than the subdominant males.

PMID- 11290723
TI  - A whole genome scan for quantitative trait loci affecting milk protein percentage
      in Israeli-Holstein cattle, by means of selective milk DNA pooling in a daughter
      design, using an adjusted false discovery rate criterion.
AB  - Selective DNA pooling was employed in a daughter design to screen all bovine
      autosomes for quantitative trait loci (QTL) affecting estimated breeding value
      for milk protein percentage (EBVP%). Milk pools prepared from high and low
      daughters of each of seven sires were genotyped for 138 dinucleotide
      microsatellites. Shadow-corrected estimates of sire allele frequencies were
      compared between high and low pools. An adjusted false discovery rate (FDR)
      method was employed to calculate experimentwise significance levels and empirical
      power. Significant associations with milk protein percentage were found for 61 of
      the markers (adjusted FDR = 0.10; estimated power, 0.68). The significant markers
      appear to be linked to 19--28 QTL. Mean allele substitution effects of the
      putative QTL averaged 0.016 (0.009--0.028) in units of the within-sire family
      standard deviation of EBVP% and summed to 0.460 EBVP%. Overall QTL heterozygosity
      was 0.40. The identified QTL appear to account for all of the variation in EBVP%
      in the population. Through use of selective DNA pooling, 4400 pool data points
      provided the statistical power of 600,000 individual data points.

PMID- 11290724
TI  - The spatial structure of sexual and cytonuclear polymorphism in the gynodioecious
      Beta vulgaris ssp. maritima: I/ at a local scale.
AB  - We have analyzed the spatial distribution of the sex phenotypes and of
      mitochondrial, chloroplast, and nuclear markers within two gynodioecious
      populations of Beta vulgaris ssp. maritima. Within both populations, sexual
      phenotype variation is controlled mainly by the cytoplasmic genotype, although in
      one study population a joint polymorphism of cytonuclear factors is clearly
      involved. In spite of contrasts in the ecology (mainly due to different
      habitats), a clear common feature in both populations is the highly patchy
      distribution of cytoplasmic haplotypes, contrasting with the wide distribution of
      nuclear diversity. This high contrast between cytoplasmic vs. nuclear spatial
      structure may have important consequences for the maintenance of gynodioecy. It
      provides opportunities for differential selection since nuclear restorer alleles
      are expected to be selected for in the presence of their specific cytoplasmic
      male sterile (CMS) type, but to be neutral (or selected against if there is a
      cost of restoration) in the absence of their CMS type. Selective processes in
      such a cytonuclear landscape may explain the polymorphism we observed at restorer
      loci for two CMS types.

PMID- 11290725
TI  - Nuclear gene dosage effects upon the expression of maize mitochondrial genes.
AB  - Each mitochondrion possesses a genome that encodes some of its own components.
      The nucleus encodes most of the mitochondrial proteins, including the polymerases
      and factors that regulate the expression of mitochondrial genes. Little is known
      about the number or location of these nuclear factors. B-A translocations were
      used to create dosage series for 14 different chromosome arms in maize plants
      with normal cytoplasm. The presence of one or more regulatory factors on a
      chromosome arm was indicated when variation of its dosage resulted in the
      alteration in the amount of a mitochondrial transcript. We used quantitative
      Northern analysis to assay the transcript levels of three mitochondrially encoded
      components of the cytochrome c oxidase complex (cox1, cox2, and cox3). Data for a
      nuclearly encoded component (cox5b) and for two mitochondrial genes that are
      unrelated to cytochrome c oxidase, ATP synthase alpha-subunit and 18S rRNA, were
      also determined. Two tissues, embryo and endosperm, were compared and most
      effects were found to be tissue specific. Significantly, the array of dosage
      effects upon mitochondrial genes was similar to what had been previously found
      for nuclear genes. These results support the concept that although mitochondrial
      genes are prokaryotic in origin, their regulation has been extensively integrated
      into the eukaryotic cell.

PMID- 11290726
TI  - Regulation of activator/dissociation transposition by replication and DNA
      methylation.
AB  - In maize the transposable elements Activator/Dissociation (Ac/Ds) transpose
      shortly after replication from one of the two resulting chromatids ("chromatid
      selectivity"). A model has been suggested that explains this phenomenon as a
      consequence of different affinity for Ac transposase binding to holo-, hemi-, and
      unmethylated transposon ends. Here we demonstrate that in petunia cells a
      holomethylated Ds is unable to excise from a nonreplicating vector and that
      replication restores excision. A Ds element hemi-methylated on one DNA strand
      transposes in the absence of replication, whereas hemi-methylation of the
      complementary strand causes a >6.3-fold inhibition of Ds excision. Consistently
      in the active hemi-methylated state, the Ds ends have a high binding affinity for
      the transposase, whereas binding to inactive ends is strongly reduced. These
      results provide strong evidence for the above-mentioned model. Moreover, in the
      absence of DNA methylation, replication enhances Ds transposition in petunia
      protoplasts >8-fold and promotes formation of a predominant excision footprint.
      Accordingly, replication also has a methylation-independent regulatory effect on
      transposition.

PMID- 11290728
TI  - High-resolution pachytene chromosome mapping of bacterial artificial chromosomes
      anchored by genetic markers reveals the centromere location and the distribution
      of genetic recombination along chromosome 10 of rice.
AB  - Large-scale physical mapping has been a major challenge for plant geneticists due
      to the lack of techniques that are widely affordable and can be applied to
      different species. Here we present a physical map of rice chromosome 10 developed
      by fluorescence in situ hybridization (FISH) mapping of bacterial artificial
      chromosome (BAC) clones on meiotic pachytene chromosomes. This physical map is
      fully integrated with a genetic linkage map of rice chromosome 10 because each
      BAC clone is anchored by a genetically mapped restriction fragment length
      polymorphism marker. The pachytene chromosome-based FISH mapping shows a superior
      resolving power compared to the somatic metaphase chromosome-based methods. The
      telomere-centromere orientation of DNA clones separated by 40 kb can be resolved
      on early pachytene chromosomes. Genetic recombination is generally evenly
      distributed along rice chromosome 10. However, the highly heterochromatic short
      arm shows a lower recombination frequency than the largely euchromatic long arm.
      Suppression of recombination was found in the centromeric region, but the
      affected region is far smaller than those reported in wheat and barley. Our FISH
      mapping effort also revealed the precise genetic position of the centromere on
      chromosome 10.

PMID- 11290727
TI  - Identification and physical localization of useful genes and markers to a major
      gene-rich region on wheat group 1S chromosomes.
AB  - The short arm of Triticeae homeologous group 1 chromosomes is known to contain
      many agronomically important genes. The objectives of this study were to
      physically localize gene-containing regions of the group 1 short arm, enrich
      these regions with markers, and study the distribution of genes and
      recombination. We focused on the major gene-rich region ("1S0.8 region") and
      identified 75 useful genes along with 93 RFLP markers by comparing 35 different
      maps of Poaceae species. The RFLP markers were tested by gel blot DNA analysis of
      wheat group 1 nullisomic-tetrasomic lines, ditelosomic lines, and four single
      break deletion lines for chromosome arm 1BS. Seventy-three of the 93 markers
      mapped to group 1 and detected 91 loci on chromosome 1B. Fifty-one of these
      markers mapped to two major gene-rich regions physically encompassing 14% of the
      short arm. Forty-one marker loci mapped to the 1S0.8 region and 10 to 1S0.5
      region. Two cDNA markers mapped in the centromeric region and the remaining 24
      loci were on the long arm. About 82% of short arm recombination was observed in
      the 1S0.8 region and 17% in the 1S0.5 region. Less than 1% recombination was
      observed for the remaining 85% of the physical arm length.

PMID- 11290729
TI  - Bayesian mapping of quantitative trait loci under complicated mating designs.
AB  - Quantitative trait loci (QTL) are easily studied in a biallelic system. Such a
      system requires the cross of two inbred lines presumably fixed for alternative
      alleles of the QTL. However, development of inbred lines can be time consuming
      and cost ineffective for species with long generation intervals and severe
      inbreeding depression. In addition, restriction of the investigation to a
      biallelic system can sometimes be misleading because many potentially important
      allelic interactions do not have a chance to express and thus fail to be
      detected. A complicated mating design involving multiple alleles mimics the
      actual breeding system. However, it is difficult to develop the statistical model
      and algorithm using the classical maximum-likelihood method. In this study, we
      investigate the application of a Bayesian method implemented via the Markov chain
      Monte Carlo (MCMC) algorithm to QTL mapping under arbitrarily complicated mating
      designs. We develop the method under a mixed-model framework where the genetic
      values of founder alleles are treated as random and the nongenetic effects are
      treated as fixed. With the MCMC algorithm, we first draw the gene flows from the
      founders to the descendants for each QTL and then draw samples of the genetic
      parameters. Finally, we are able to simultaneously infer the posterior
      distribution of the number, the additive and dominance variances, and the
      chromosomal locations of all identified QTL.

PMID- 11290730
TI  - Genetic and nongenetic bases for the L-shaped distribution of quantitative trait
      loci effects.
AB  - The L-shaped distribution of estimated QTL effects (R(2)) has long been reported.
      We recently showed that a metabolic mechanism could account for this phenomenon.
      But other nonexclusive genetic or nongenetic causes may contribute to generate
      such a distribution. Using analysis and simulations of an additive genetic model,
      we show that linkage disequilibrium between QTL, low heritability, and small
      population size may also be involved, regardless of the gene effect distribution.
      In addition, a comparison of the additive and metabolic genetic models revealed
      that estimates of the QTL effects for traits proportional to metabolic flux are
      far less robust than for additive traits. However, in both models the highest
      R(2)'s repeatedly correspond to the same set of QTL.

PMID- 11290731
TI  - Enhanced efficiency of quantitative trait loci mapping analysis based on
      multivariate complexes of quantitative traits.
AB  - An approach to increase the efficiency of mapping quantitative trait loci (QTL)
      was proposed earlier by the authors on the basis of bivariate analysis of
      correlated traits. The power of QTL detection using the log-likelihood ratio (LOD
      scores) grows proportionally to the broad sense heritability. We found that this
      relationship holds also for correlated traits, so that an increased bivariate
      heritability implicates a higher LOD score, higher detection power, and better
      mapping resolution. However, the increased number of parameters to be estimated
      complicates the application of this approach when a large number of traits are
      considered simultaneously. Here we present a multivariate generalization of our
      previous two-trait QTL analysis. The proposed multivariate analogue of QTL
      contribution to the broad-sense heritability based on interval-specific
      calculation of eigenvalues and eigenvectors of the residual covariance matrix
      allows prediction of the expected QTL detection power and mapping resolution for
      any subset of the initial multivariate trait complex. Permutation technique
      allows chromosome-wise testing of significance for the whole trait complex and
      the significance of the contribution of individual traits owing to: (a) their
      correlation with other traits, (b) dependence on the chromosome in question, and
      (c) both a and b. An example of application of the proposed method on a real data
      set of 11 traits from an experiment performed on an F(2)/F(3) mapping population
      of tetraploid wheat (Triticum durum x T. dicoccoides) is provided.

PMID- 11290732
TI  - On the origin of self-incompatibility haplotypes: transition through self
      compatible intermediates.
AB  - Self-incompatibility (SI) in flowering plants entails the inhibition of
      fertilization by pollen that express specificities in common with the pistil. In
      species of the Solanaceae, Rosaceae, and Scrophulariaceae, the inhibiting factor
      is an extracellular ribonuclease (S-RNase) secreted by stylar tissue. A distinct
      but as yet unknown gene (provisionally called pollen-S) appears to determine the
      specific S-RNase from which a pollen tube accepts inhibition. The S-RNase gene
      and pollen-S segregate with the classically defined S-locus. The origin of a new
      specificity appears to require, at minimum, mutations in both genes. We explore
      the conditions under which new specificities may arise from an intermediate state
      of loss of self-recognition. Our evolutionary analysis of mutations that affect
      either pistil or pollen specificity indicates that natural selection favors
      mutations in pollen-S that reduce the set of pistils from which the pollen
      accepts inhibition and disfavors mutations in the S-RNase gene that cause the
      nonreciprocal acceptance of pollen specificities. We describe the range of
      parameters (rate of receipt of self-pollen and relative viability of inbred
      offspring) that permits the generation of a succession of new specificities. This
      evolutionary pathway begins with the partial breakdown of SI upon the appearance
      of a mutation in pollen-S that frees pollen from inhibition by any S-RNase
      presently in the population and ends with the restoration of SI by a mutation in
      the S-RNase gene that enables pistils to reject the new pollen type.

PMID- 11290733
TI  - Prediction of total genetic value using genome-wide dense marker maps.
AB  - Recent advances in molecular genetic techniques will make dense marker maps
      available and genotyping many individuals for these markers feasible. Here we
      attempted to estimate the effects of approximately 50,000 marker haplotypes
      simultaneously from a limited number of phenotypic records. A genome of 1000 cM
      was simulated with a marker spacing of 1 cM. The markers surrounding every 1-cM
      region were combined into marker haplotypes. Due to finite population size N(e) =
      100, the marker haplotypes were in linkage disequilibrium with the QTL located
      between the markers. Using least squares, all haplotype effects could not be
      estimated simultaneously. When only the biggest effects were included, they were
      overestimated and the accuracy of predicting genetic values of the offspring of
      the recorded animals was only 0.32. Best linear unbiased prediction of haplotype
      effects assumed equal variances associated to each 1-cM chromosomal segment,
      which yielded an accuracy of 0.73, although this assumption was far from true.
      Bayesian methods that assumed a prior distribution of the variance associated
      with each chromosome segment increased this accuracy to 0.85, even when the prior
      was not correct. It was concluded that selection on genetic values predicted from
      markers could substantially increase the rate of genetic gain in animals and
      plants, especially if combined with reproductive techniques to shorten the
      generation interval.

PMID- 11290735
TI  - Tuberin phosphorylation regulates its interaction with hamartin. Two proteins
      involved in tuberous sclerosis.
AB  - Hamartin and tuberin are products of the tumor suppressor genes, TSC1 and TSC2,
      respectively. When mutated, a characteristic spectrum of tumor-like growths
      develop resulting in the syndrome of tuberous sclerosis complex. The phenotypes
      associated with TSC1 and TSC2 mutations are largely indistinguishable suggesting
      a common biochemical pathway. Indeed, hamartin and tuberin have been shown to
      interact stably in vitro and in vivo. Factors that regulate their interaction are
      likely critical to the understanding of disease pathogenesis. In this study, we
      showed that tuberin is phosphorylated at serine and tyrosine residues in response
      to serum and other factors, and it undergoes serial phosphorylation that can be
      detected by differences in electrophoretic mobilities. A disease-related TSC2
      mutation (Y1571H) nearly abolished tuberin phosphorylation when stimulated with
      pervanadate. Expression of this mutant tuberin caused a marked reduction in TSC1
      TSC2 interaction compared with wild-type protein and significantly curtailed the
      growth inhibitory effects of tuberin when overexpressed in COS1 cells, consistent
      with a loss of function mutation. Examination of a second pathologic mutation,
      P1675L, revealed a similar relationship between limited phosphorylation and
      reduced interaction with hamartin. Our data show for the first time that 1)
      tuberin is phosphorylated at tyrosine and serine residues, 2) TSC1-TSC2
      interaction is regulated by tuberin phosphorylation, and 3) defective
      phosphorylation of tuberin is associated with loss of its tumor suppressor
      activity. These findings suggest that phosphorylation may be a key regulatory
      mechanism controlling TSC1-TSC2 function.

PMID- 11290736
TI  - Salivary acinar cells from aquaporin 5-deficient mice have decreased membrane
      water permeability and altered cell volume regulation.
AB  - Aquaporins (AQPs) are channel proteins that regulate the movement of water
      through the plasma membrane of secretory and absorptive cells in response to
      osmotic gradients. In the salivary gland, AQP5 is the major aquaporin expressed
      on the apical membrane of acinar cells. Previous studies have shown that the
      volume of saliva secreted by AQP5-deficient mice is decreased, indicating a role
      for AQP5 in saliva secretion; however, the mechanism by which AQP5 regulates
      water transport in salivary acinar cells remains to be determined. Here we show
      that the decreased salivary flow rate and increased tonicity of the saliva
      secreted by Aqp5(-)/- mice in response to pilocarpine stimulation are not caused
      by changes in whole body fluid homeostasis, indicated by similar blood gas and
      electrolyte concentrations in urine and blood in wild-type and AQP5-deficient
      mice. In contrast, the water permeability in parotid and sublingual acinar cells
      isolated from Aqp5(-)/- mice is decreased significantly. Water permeability
      decreased by 65% in parotid and 77% in sublingual acinar cells from Aqp5(-)/-
      mice in response to hypertonicity-induced cell shrinkage and hypotonicity-induced
      cell swelling. These data show that AQP5 is the major pathway for regulating the
      water permeability in acinar cells, a critical property of the plasma membrane
      which determines the flow rate and ionic composition of secreted saliva.

PMID- 11290737
TI  - The 3' --> 5' exonuclease of T4 DNA polymerase removes premutagenic alkyl
      mispairs and contributes to futile cycling at O6-methylguanine lesions.
AB  - We have studied the processing of O(6)-methylguanine (m6G)-containing
      oligonucleotides and N-methyl-N-nitrosourea (MNU)-treated DNA templates by the 3'
      --> 5' exonuclease of T4 DNA polymerase. In vitro biochemical analyses
      demonstrate that the exonuclease can remove bases opposite a defined m6G lesion.
      The efficiency of excision of a terminal m6G.T was similar to that of m6G.C, and
      both were excised as efficiently as a G.T substrate. Partitioning assays between
      the polymerase and exonuclease activities, performed in the presence of dNTPs,
      resulted in repeated incorporation and excision events opposite the m6G lesion.
      This idling produces dramatically less full-length product, relative to natural
      substrates, indicating that the 3' --> 5' exonuclease may contribute to DNA
      synthesis inhibition by alkylating agents. Genetic data obtained using an in
      vitro herpes simplex virus-thymidine kinase assay support the inefficiency of the
      exonuclease as a "proofreading" activity for m6G, since virtually all mutations
      produced by the native enzyme using MNU-treated templates were G --> A
      transitions. Comparison of MNU dose-response curves for exonuclease-proficient
      and -deficient forms of T4 polymerase reveals that the exonuclease efficiently
      removes 50-86% of total premutagenic alkyl mispairs. We propose that idling of
      exonuclease-proficient polymerases at m6G lesions during repair DNA synthesis
      provides the biochemical explanation for cellular cytotoxicity of methylating
      agents.

PMID- 11290738
TI  - Feedback inhibition of amidophosphoribosyltransferase regulates the rate of cell
      growth via purine nucleotide, DNA, and protein syntheses.
AB  - To clarify the contributions of amidophosphoribosyltransferase (ATase) and its
      feedback regulation to the rates of purine de novo synthesis, DNA synthesis,
      protein synthesis, and cell growth, mutated human ATase (mhATase) resistant to
      feedback inhibition by purine ribonucleotides was engineered by site-directed
      mutagenesis and expressed in CHO ade (-)A cells (an ATase-deficient cell line of
      Chinese hamster ovary fibroblasts) and in transgenic mice (mhATase-Tg mice). In
      Chinese hamster ovary transfectants with mhATase, the following parameters were
      examined: ATase activity and its subunit structure, the metabolic rates of de
      novo and salvage pathways, DNA and protein synthesis rates, and the rate of cell
      growth. In mhATase-Tg mice, ATase activity in the liver and spleen, the metabolic
      rate of the de novo pathway in the liver, serum uric acid concentration, urinary
      excretion of purine derivatives, and T lymphocyte proliferation by
      phytohemagglutinin were examined. We concluded the following. 1) ATase and its
      feedback inhibition regulate not only the rate of purine de novo synthesis but
      also DNA and protein synthesis rates and the rate of cell growth in cultured
      fibroblasts. 2) Suppression of the de novo pathway by the salvage pathway is
      mainly due to the feedback inhibition of ATase by purine ribonucleotides produced
      via the salvage pathway, whereas the suppression of the salvage pathway by the de
      novo pathway is due to consumption of 5-phosphoribosyl 1-pyrophosphate by the de
      novo pathway. 3) The feedback inhibition of ATase is more important for the
      regulation of the de novo pathway than that of 5-phosphoribosyl 1-pyrophosphate
      synthetase. 4) ATase superactivity leads to hyperuricemia and an increased
      bromodeoxyuridine incorporation in T lymphocytes stimulated by
      phytohemagglutinin.

PMID- 11290739
TI  - Distinct functions of the ATP binding cassettes of transporters associated with
      antigen processing: a mutational analysis of Walker A and B sequences.
AB  - The transporters associated with antigen processing (TAP1/TAP2) provide peptides
      to MHC class I molecules in the endoplasmic reticulum. Like other ATP-binding
      cassette proteins, TAP uses ATP hydrolysis to power transport. We have studied
      peptide binding to as well as translocation by TAP proteins with mutations in the
      Walker A and B sequences that are known to mediate ATP binding and hydrolysis. We
      show that a mutation in the TAP1 Walker B sequence reported to abrogate class I
      expression by a lung tumor does not affect ATP binding affinity, suggesting a
      defect restricted to ATP hydrolysis. This mutation reduces peptide transport by
      only 50%, suggesting that TAP function can be highly limiting for antigen
      presentation in non-lymphoid cells. Single substitutions in Walker A sequences
      (TAP1K544A, TAP2K509A), or their complete replacements, abrogate nucleotide
      binding to each subunit. Although all of these mutations abrogate peptide
      transport, they reveal distinct roles for nucleotide binding to the two
      transporter subunits in TAP folding and in regulation of peptide substrate
      affinity, respectively. Alteration of the TAP1 Walker A motif can have strong
      effects on TAP1 and thereby TAP complex folding. However, TAP1 Walker A mutations
      compatible with correct folding do not affect peptide binding. In contrast,
      abrogation of the TAP2 nucleotide binding capacity has little or no effect on TAP
      folding but eliminates peptide binding to TAP at 37 degrees C in the presence of
      nucleotides. Thus, nucleotide binding to TAP2 but not to TAP1 is a prerequisite
      for peptide binding to TAP. Based on these results, we propose a model in which
      nucleotide and peptide release from TAP are coupled and followed by ATP binding
      to TAP2, which induces high peptide affinity and initiates the transport cycle.

PMID- 11290740
TI  - The Ataxia telangiectasia gene product is required for oxidative stress-induced
      G1 and G2 checkpoint function in human fibroblasts.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by
      neuronal degeneration accompanied by ataxia, telangiectasias, acute cancer
      predisposition, and sensitivity to ionizing radiation (IR). Cells from
      individuals with AT show unusual sensitivity to IR, severely attenuated cell
      cycle checkpoint functions, and poor p53 induction in response to IR compared
      with normal human fibroblasts (NHFs). The gene mutated in AT (ATM) has been
      cloned, and its product, pATM, has IR-inducible kinase activity. The AT phenotype
      has been suggested to be a consequence, at least in part, of an inability to
      respond appropriately to oxidative damage. To test this hypothesis, we examined
      the ability of NHFs and AT dermal fibroblasts to respond to t-butyl hydroperoxide
      and IR treatment. AT fibroblasts exhibit, in comparison to NHFs, increased
      sensitivity to the toxicity of t-butyl hydroperoxide, as measured by colony
      forming efficiency assays. Unlike NHFs, AT fibroblasts fail to show G(1) and G(2)
      phase checkpoint functions or to induce p53 in response to t-butyl hydroperoxide.
      Treatment of NHFs with t-butyl hydroperoxide activates pATM-associated kinase
      activity. Our results indicate that pATM is involved in responding to certain
      aspects of oxidative damage and in signaling this information to downstream
      effectors of the cell cycle checkpoint functions. Our data further suggest that
      some of the pathologies seen in AT could arise as a consequence of an inability
      to respond normally to oxidative damage.

PMID- 11290742
TI  - Sturgeon orphanin, a molecular "fossil" that bridges the gap between the opioids
      and orphanin FQ/nociceptin.
AB  - The elucidation of the cDNA sequence for sturgeon proorphanin provides a unique
      window for interpreting the evolutionary history of the opioid/orphanin gene
      family. The molecular "fossil" status of this precursor can be seen in several
      ancestral sequence characteristics that point to its origin as a duplication of
      either a prodynorphin- or proenkephalin-like gene. The sturgeon proorphanin cDNA
      encodes a precursor protein of 194 residues, and the orphanin heptadecapeptide
      itself binds not only the opioid receptor-like 1 (ORL1) receptor but also the
      classical (mu, kappa, and delta) opioid receptors with near equal affinity.
      Allowing for this broad receptor specificity are several amino acid substitutions
      at key positions in the heptadecapeptide sequence, relative to its mammalian
      orthologs, that have been linked by amino acid scans and site-directed mutagenic
      studies to the exclusion of mammalian orphanin FQ/nociceptin from classic opioid
      ligands (i.e. F1Y and L14W). The unique receptor binding profile of sturgeon
      orphanin not only provides insight into the evolutionary history of the opioid
      and opioid-related peptides but also provides an ideal context in which to
      investigate the underlying mechanisms by which novel and often divergent
      physiological functions arise in receptor-ligand systems.

PMID- 11290741
TI  - Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene
      targeted mice and abolition of a widespread pathway of steroid and oxysterol
      hydroxylation.
AB  - The major adrenal steroid dehydroepiandrosterone (DHEA) enhances memory and
      immune function but has no known dedicated receptor; local metabolism may govern
      its activity. We described a cytochrome P450 expressed in brain and other
      tissues, CYP7B, that catalyzes the 7alpha-hydroxylation of oxysterols and 3beta
      hydroxysteroids including DHEA. We report here that CYP7B mRNA and 7alpha
      hydroxylation activity are widespread in rat tissues. However, steroids related
      to DHEA are reported to be modified at positions other than 7alpha, exemplified
      by prominent 6alpha-hydroxylation of 5alpha-androstane-3beta,17beta-diol
      (A/anediol) in some rodent tissues including brain. To determine whether CYP7B is
      responsible for these and other activities we disrupted the mouse Cyp7b gene by
      targeted insertion of an IRES-lacZ reporter cassette, placing reporter enzyme
      activity (beta-galactosidase) under Cyp7b promoter control. In heterozygous mouse
      brain, chromogenic detection of reporter activity was strikingly restricted to
      the dentate gyrus. Staining did not exactly reproduce the in situ hybridization
      expression pattern; post-transcriptional control is inferred. Lower level
      staining was detected in cerebellum, liver, and kidney, and which largely
      paralleled mRNA distribution. Liver and kidney expression was sexually dimorphic.
      Mice homozygous for the insertion are viable and superficially normal, but ex
      vivo metabolism of DHEA to 7alpha-hydroxy-DHEA was abolished in brain, spleen,
      thymus, heart, lung, prostate, uterus, and mammary gland; lower abundance
      metabolites were also eliminated. 7alpha-Hydroxylation of 25-hydroxycholesterol
      and related substrates was also abolished, as was presumed 6alpha-hydroxylation
      of A/anediol. These different enzyme activities therefore derive from the Cyp7b
      gene. CYP7B is thus a major extrahepatic steroid and oxysterol hydroxylase and
      provides the predominant route for local metabolism of DHEA and related molecules
      in brain and other tissues.

PMID- 11290743
TI  - Proteomic analysis of macrophage differentiation. p46/52(Shc) Tyrosine
      phosphorylation is required for CSF-1-mediated macrophage differentiation.
AB  - Macrophage colony stimulating factor (M-CSF or CSF-1) acts to regulate the
      development and function of cells of the macrophage lineage. Murine myeloid FDC
      P1 cells transfected with the CSF-1 receptor (FD/WT) adopt a macrophage-like
      morphology when cultured in CSF-1. This process is abrogated in FDC-P1 cells
      transfected with the CSF-1 receptor with a tyrosine to phenyalanine substitution
      at position 807 (FD/807), suggesting that a molecular interaction critical to
      differentiation signaling is lost (Bourette, R. P., Myles, G. M., Carlberg, K.,
      Chen, A. R., and Rohrschneider, L. R. (1995) Cell Growth Differ. 6, 631--645). A
      detailed examination of lysates of CSF-1-treated FD/807 cells by two-dimensional
      SDS-polyacrylamide gel electrophoresis (PAGE) revealed a number of proteins whose
      degree of tyrosine phosphorylation was modulated by the Y807F mutation. Included
      in this category were three phosphorylated proteins that co-migrated with
      p46/52(Shc). Immunoprecipitation, Western blotting, and in vitro binding studies
      suggest that they are indeed p46/52(Shc). A key regulator of differentiation in a
      number of cell systems, ERK was observed to exhibit an activity that correlated
      with the relative degree of differentiation induced by CSF-1 in the two cell
      types. Transfection of cells with a non-tyrosine-phosphorylatable form of
      p46/52(Shc) prevented the normally observed CSF-1-mediated macrophage
      differentiation as determined by adoption of macrophage-like morphology and
      expression of the monocyte/macrophage lineage cell surface marker, Mac-1. These
      results are the first to suggest that p46/52(Shc) may play a role in CSF-1
      induced macrophage differentiation. Additionally, a number of proteins were
      identified by two-dimensional SDS-PAGE whose degree of tyrosine phosphorylation
      is also modulated by the Y807F substitution. This group of molecules may contain
      novel signaling molecules important in macrophage differentiation.

PMID- 11290745
TI  - Crystal structure of Bacillus subtilis isocitrate dehydrogenase at 1.55 A.
      Insights into the nature of substrate specificity exhibited by Escherichia coli
      isocitrate dehydrogenase kinase/phosphatase.
AB  - Isocitrate dehydrogenase from Bacillus subtilis (BsIDH) is a member of a family
      of metal-dependent decarboxylating dehydrogenases. Its crystal structure was
      solved to 1.55 A and detailed comparisons with the homologue from Escherichia
      coli (EcIDH), the founding member of this family, were made. Although the two
      IDHs are structurally similar, there are three notable differences between them.
      First, a mostly nonpolar beta-strand and two connecting loops in the small domain
      of EcIDH are replaced by two polar alpha-helices in BsIDH. Because of a 13
      residue insert in this region of BsIDH, these helices protrude over the active
      site cleft of the opposing monomer. Second, a coil leading into this cleft, the
      so-called "phosphorylation" loop, is bent inward in the B. subtilis enzyme,
      narrowing the entrance to the active site from about 12 to 4 A. Third, although
      BsIDH is a homodimer, the two unique crystallographic subunits of BsIDH are not
      structurally identical. The two monomers appear to differ by a domain shift of
      the large domain relative to the small domain/clasp region, reminiscent of what
      has been observed in the open/closed conformations of EcIDH. In Escherichia coli,
      IDH is regulated by reversible phosphorylation by the bifunctional enzyme IDH
      kinase/phosphatase (IDH-K/P). The site of phosphorylation is Ser(113), which lies
      deep within the active site crevice. Structural differences between EcIDH and
      BsIDH may explain disparities in their abilities to act as substrates for IDH
      K/P.

PMID- 11290744
TI  - Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin.
AB  - The Na(+)/I(-) symporter (NIS) is a key plasma membrane glycoprotein that
      mediates active I(-) transport in the thyroid gland (Dai, G., Levy, O., and
      Carrasco, N. (1996) Nature 379, 458-460), the first step in thyroid hormone
      biogenesis. Whereas relatively little is known about the mechanisms by which
      thyrotropin (TSH), the main hormonal regulator of thyroid function, regulates NIS
      activity, post-transcriptional events have been suggested to play a role
      (Kaminsky, S. M., Levy, O., Salvador, C., Dai, G., and Carrasco, N. (1994) Proc.
      Natl. Acad. Sci. U. S. A. 91, 3789-3793). Here we show that TSH induces de novo
      NIS biosynthesis and modulates the long NIS half-life ( approximately 5 days). In
      addition, we demonstrate that TSH is required for NIS targeting to or retention
      in the plasma membrane. We further show that NIS is a phosphoprotein and that TSH
      modulates its phosphorylation pattern. These results provide strong evidence of
      the major role played by post-transcriptional events in the regulation of NIS by
      TSH. Beyond their inherent interest, it is also of medical significance that
      these TSH-dependent regulatory mechanisms may be altered in the large proportion
      of thyroid cancers in which NIS is predominantly expressed in intracellular
      compartments, instead of being properly targeted to the plasma membrane.

PMID- 11290746
TI  - The function of interdomain interactions in controlling nucleotide exchange rates
      in transducin.
AB  - The intramolecular contacts in heterotrimeric G proteins that determine the rates
      of basal and receptor-stimulated nucleotide exchange are not fully understood.
      The alpha subunit of heterotrimeric G proteins consists of two domains: a Ras
      like domain with structural homology to the monomeric G protein Ras and a helical
      domain comprised of six alpha-helices. The bound nucleotide lies in a deep cleft
      between the two domains. Exchange of the bound nucleotide may involve opening of
      this cleft. Thus interactions between the domains may affect the rate of
      nucleotide exchange in G proteins. We have tested this hypothesis in the alpha
      subunit of the rod cell G protein transducin (Galpha(t)). Site-directed mutations
      were prepared in a series of residues located at the interdomain interface. The
      proteins were expressed in vitro in a reticulocyte lysate system. The rates of
      basal and rhodopsin-catalyzed nucleotide exchange were determined using a trypsin
      digestion assay specifically adapted for kinetic measurements. Charge-altering
      substitutions of two residues at the interdomain interface, Lys(273) and
      Lys(276), increased basal nucleotide exchange rates modestly (5-10-fold).
      However, we found no evidence that interactions spanning the two domains in
      Galpha(t) significantly affected either basal or rhodopsin-catalyzed nucleotide
      exchange rates. These results suggest that opening of the interdomain cleft is
      not an energetic barrier to nucleotide exchange in Galpha(t). Experiments with
      Galpha(i1) suggest by comparison that the organization and function of the
      interdomain region differ among various G protein subtypes.

PMID- 11290747
TI  - Epidermal growth factor (EGF) receptor-dependent ERK activation by G protein
      coupled receptors: a co-culture system for identifying intermediates upstream and
      downstream of heparin-binding EGF shedding.
AB  - "Transactivation" of epidermal growth factor receptors (EGFRs) in response to
      activation of many G protein-coupled receptors (GPCRs) involves
      autocrine/paracrine shedding of heparin-binding EGF (HB-EGF). HB-EGF shedding
      involves proteolytic cleavage of a membrane-anchored precursor by incompletely
      characterized matrix metalloproteases. In COS-7 cells, alpha(2A)-adrenergic
      receptors (ARs) stimulate ERK phosphorylation via two distinct pathways, a
      transactivation pathway that involves the release of HB-EGF and the EGFR and an
      alternate pathway that is independent of both HB-EGF and the EGFR. We have
      developed a mixed culture system to study the mechanism of GPCR-mediated HB-EGF
      shedding in COS-7 cells. In this system, alpha(2A)AR expressing "donor" cells are
      co-cultured with "acceptor" cells lacking the alpha(2A)AR. Each population
      expresses a uniquely epitope-tagged ERK2 protein, allowing the selective
      measurement of ERK activation in the donor and acceptor cells. Stimulation with
      the alpha(2)AR selective agonist UK14304 rapidly increases ERK2 phosphorylation
      in both the donor and the acceptor cells. The acceptor cell response is sensitive
      to inhibitors of both the EGFR and HB-EGF, indicating that it results from the
      release of HB-EGF from the alpha(2A)AR-expressing donor cells. Experiments with
      various chemical inhibitors and dominant inhibitory mutants demonstrate that EGFR
      dependent activation of the ERK cascade after alpha(2A)AR stimulation requires
      Gbetagamma subunits upstream and dynamin-dependent endocytosis downstream of HB
      EGF shedding and EGFR activation, whereas Src kinase activity is required both
      for the release of HB-EGF and for HB-EGF-mediated ERK2 phosphorylation.

PMID- 11290749
TI  - A sulfurtransferase is required in the transfer of cysteine sulfur in the in
      vitro synthesis of molybdopterin from precursor Z in Escherichia coli.
AB  - It has been shown that conversion of precursor Z to molybdopterin (MPT) by
      Escherichia coli MPT synthase entails the transfer of the sulfur atom of the C
      terminal thiocarboxylate from the small subunit of the synthase to generate the
      dithiolene group of MPT and that the moeB mutant of E. coli contains inactive MPT
      synthase devoid of the thiocarboxylate. The data presented here demonstrate that
      l-cysteine can serve as the source of the sulfur for the biosynthesis of MPT in
      vitro but only in the presence of a persulfide-containing sulfurtransferase such
      as IscS, cysteine sulfinate desulfinase (CSD), or CsdB. A fully defined in vitro
      system has been developed in which an inactive form of MPT synthase can be
      activated by incubation with MoeB, Mg-ATP, l-cysteine, and one of the NifS-like
      sulfurtransferases, and the addition of precursor Z to the in vitro system gives
      rise to MPT formation. The use of radiolabeled l-[(35)S]cysteine has demonstrated
      that both sulfurs of the dithiolene group of MPT originate from l-cysteine. It
      was found that MPT can be produced from precursor Z in an E. coli iscS mutant
      strain, indicating that IscS is not required for the in vivo sulfuration of MPT
      synthase. A comparison of the ability of the three sulfurtransferases to provide
      the sulfur for MPT formation showed the highest activity for CSD in the in vitro
      system.

PMID- 11290748
TI  - Glutaredoxin protects cerebellar granule neurons from dopamine-induced apoptosis
      by dual activation of the ras-phosphoinositide 3-kinase and jun n-terminal kinase
      pathways.
AB  - Glutaredoxin 2 (Grx2) from Escherichia coli protects cerebellar neurons from
      dopamine-induced apoptosis via nuclear factor kappa B (NF-kappaB) activation,
      which is mediated by the expression of redox factor-1 (Ref-1). An analysis of the
      mechanisms underlying Grx2 protective activity revealed dual activation of signal
      transduction pathways. Grx2 significantly activated the Ras/phosphoinositide 3
      kinase/Akt/NF-kappaB cascade in parallel to the Jun N-terminal kinase (JNK)/AP1
      cascade. Dopamine, in comparison, down-regulated both pathways. Treatment of
      neurons with Ref-1 antisense oligonucleotide reduced the ability of Grx2 to
      activate Akt and AP-1 but had no effect on the phosphorylation of JNK1/2,
      suggesting that Akt/NF-kappaB and AP-1 are regulated by Ref-1. Exposure of the
      neurons to JNK1/2 antisense oligonucleotide in the presence of Grx2 significantly
      reduced AP-1 and NF-kappaB DNA binding activities and abolished Grx2 protection.
      These results demonstrate that dual activation of Ras/phosphoinositide 3-kinase
      and AP-1 cascades, which are mediated by Ref-1, is an essential component of the
      Grx2 mechanism of action.

PMID- 11290750
TI  - Design and production of active cellulosome chimeras. Selective incorporation of
      dockerin-containing enzymes into defined functional complexes.
AB  - Defined chimeric cellulosomes were produced in which selected enzymes were
      incorporated in specific locations within a multicomponent complex. The molecular
      building blocks of this approach are based on complementary protein modules from
      the cellulosomes of two clostridia, Clostridium thermocellum and Clostridium
      cellulolyticum, wherein cellulolytic enzymes are incorporated into the complexes
      by means of high-affinity species-specific cohesin-dockerin interactions. To
      construct the desired complexes, a series of chimeric scaffoldins was prepared by
      recombinant means. The scaffoldin chimeras were designed to include two cohesin
      modules from the different species, optionally connected to a cellulose-binding
      domain. The two divergent cohesins exhibited distinct specificities such that
      each recognized selectively and bound strongly to its dockerin counterpart. Using
      this strategy, appropriate dockerin-containing enzymes could be assembled
      precisely and by design into a desired complex. Compared with the mixture of free
      cellulases, the resultant cellulosome chimeras exhibited enhanced synergistic
      action on crystalline cellulose.

PMID- 11290751
TI  - The cathepsin B inhibitor z-FA.fmk inhibits cytokine production in macrophages
      stimulated by lipopolysaccharide.
AB  - Cathepsin B has previously been shown to proteolytically activate the
      proinflammatory caspase-11 in vitro. Here we show that cathepsin B is not
      involved in activation of caspase-11 induced by lipopolysaccharide (LPS) and
      subsequent maturation of interleukin (IL)-1beta in macrophages. Nevertheless, we
      found that the cathepsin B inhibitor benzyloxycarbonyl-Phe-Ala-fluoromethylketone
      (z-FA.fmk) prevents LPS-induced production of IL-1alpha, IL-1beta, and tumor
      necrosis factor at the transcriptional level. The latter was not because of
      cathepsin B inhibition, but was mediated by inhibition of the transactivation
      potential of the nuclear factor kappaB (NF-kappaB). z-FA.fmk did not prevent LPS
      induced activation of p38 mitogen-activated protein kinase, which was shown to be
      involved in NF-kappaB transactivation in response to LPS. These results suggest
      that the previously described therapeutic effect of z-FA.fmk in the treatment of
      rheumatoid arthritis might not only result from inhibition of cathepsin B but
      also implicates an important contribution from the inhibition of NF-kappaB
      dependent gene expression.

PMID- 11290753
TI  - Cutting edge: recombinant adenoviruses induce CD8 T cell responses to an inserted
      protein whose expression is limited to nonimmune cells.
AB  - CD8 T cells (T(CD8+)) play a crucial role in immunity to viruses. Current
      understanding of activation of naive T cells entails Ag presentation by
      professional APCs (pAPCs). What happens, however, when viruses evolve to avoid
      infecting pAPCs? We have studied the consequences of this strategy by generating
      recombinant adenoviruses that express influenza A virus nucleoprotein under the
      control of tissue-specific promoters. We show that the immunogenicity of such
      viruses requires their delivery to organs capable of expressing nucleoprotein.
      This indicates that infection of pAPCs is not required for adenoviruses to elicit
      a T(CD8+) response, probably due to a cross-priming via pAPCs. While this bodes
      well for recombinant adenoviruses as vaccines, it dims their prospects as gene
      therapy vectors.

PMID- 11290752
TI  - Identification of common binding sites for calmodulin and inositol 1,4,5
      trisphosphate receptors on the carboxyl termini of trp channels.
AB  - Homologues of Drosophila Trp (transient receptor potential) form plasma membrane
      channels that mediate Ca(2+) entry following the activation of phospholipase C by
      cell surface receptors. Among the seven Trp homologous found in mammals, Trp3 has
      been shown to interact with and respond to IP(3) receptors (IP(3)Rs) for
      activation. Here we show that Trp4 and other Trp proteins also interact with
      IP(3)Rs. The IP(3)R-binding domain also interacts with calmodulin (CaM) in a
      Ca(2+)-dependent manner with affinities ranging from 10 nm for Trp2 to 290 nm for
      Trp6. In addition, other binding sites for CaM and IP(3)Rs are present in the
      alpha but not the beta isoform of Trp4. In the presence of Ca(2+), the Trp-IP(3)R
      interaction is inhibited by CaM. However, a synthetic peptide representing a Trp
      binding domain of IP(3)Rs inhibited the binding of CaM to Trp3, -6, and -7 more
      effectively than that to Trp1, -2, -4, and -5. In inside-out membrane patches,
      Trp4 is activated strongly by calmidazolium, an antagonist of CaM, and a high (50
      microm) but not a low (5 microm) concentration of the Trp-binding peptide of the
      IP(3)R. Our data support the view that both CaM and IP(3)Rs play important roles
      in controlling the gating of Trp-based channels. However, the sensitivity and
      responses to CaM and IP(3)Rs differ for each Trp.

PMID- 11290754
TI  - Cutting edge: eotaxin elicits rapid vesicular transport-mediated release of
      preformed IL-4 from human eosinophils.
AB  - IL-4 release is important in promoting Th2-mediated allergic and parasitic immune
      responses. Although human eosinophils are potential sources of IL-4, physiologic
      mechanisms to elicit its release have not been established. By flow cytometry and
      microscopy, eosinophils from normal donors uniformly contained preformed IL-4. In
      contrast to cytolytic IL-4 release from calcium ionophore-activated eosinophils,
      eotaxin and RANTES, but not IFN-gamma, elicited IL-4 release by noncytotoxic
      mechanisms. With a dual Ab capture and detection immunofluorescent microscopic
      assay, IL-4 was released at discrete cell surface sites. IL-5 enhanced eotaxin
      induced IL-4 release, which was mediated by G protein-coupled CCR3 receptors,
      detectable as early as 5 min and maximum within 1 h. IL-4 release was not
      diminished by transcription or protein synthesis inhibitors, but was suppressed
      by brefeldin A, an inhibitor of vesicle formation. Thus, CCR3-mediated signaling
      can rapidly mobilize IL-4 stored preformed in human eosinophils for release by
      vesicular transport to contribute to immune responses.

PMID- 11290755
TI  - Cutting edge: characterization of allorestricted and peptide-selective
      alloreactive T cells using HLA-tetramer selection.
AB  - The vast majority of alloreactive T cells recognize foreign MHC molecules in a
      peptide-dependent manner. A subpopulation of these peptide-dependent alloreactive
      T cells is peptide-specific and contains T cells that are of interest for tumor
      immunotherapy. Allorestricted T cells (i.e., peptide-specific and alloreactive)
      specific for tumor-associated Ags can be raised in vitro. However, it is
      technically difficult to distinguish between peptide-specific and peptide
      nonspecific alloreactive T cells by functional assays in vitro. Here we show for
      the first time that allorestricted T cells specifically bind HLA-peptide
      tetrameric complexes, as nominal Ag-specific T cells would do. In consequence,
      fluorescent HLA-peptide tetrameric complexes can be used for sorting and cloning
      of allorestricted CTLs specific for a peptide of interest. We also show by the
      mean of HLA-peptide tetramers the existence of peptide-selective alloreactive T
      cells that recognize a conformation on the foreign-MHC brought about by some but
      not all peptides bound.

PMID- 11290756
TI  - Cutting edge: evidence for a signaling partnership between urokinase receptors
      (CD87) and L-selectin (CD62L) in human polymorphonuclear neutrophils.
AB  - Leukocyte urokinase plasminogen activator receptors (uPARs) cluster at adhesion
      interfaces and at migratory fronts where they participate in adhesion,
      chemotaxis, and proteolysis. uPAR aggregation triggers activation signaling even
      though this glycolipid-anchored protein must associate with membrane-spanning
      proteins to access the cell interior. This study demonstrates a novel partnership
      between uPAR and L-selectin in human polymorphonuclear neutrophils. Fluorescence
      resonance energy transfer demonstrated a direct physical association between uPAR
      and L-selectin. To examine the role of L-selectin in uPAR-mediated signaling,
      uPAR was cross-linked and intracellular Ca(2+) concentrations were measured by
      spectrofluorometry. A mAb reactive against the carbohydrate binding domain (CBD)
      of L-selectin substantially inhibited uPAR-mediated Ca(2+) mobilization, whereas
      mAbs against the beta(2) integrin complement receptor 3 (CR3), another uPAR
      binding adhesion protein, had no effect. Similarly, fucoidan, a sulfated
      polysaccharide that binds to L-selectin CBD, inhibited the Ca(2+) signal. We
      conclude that uPAR associates with the CBD region of L-selectin to form a
      functional signaling complex.

PMID- 11290757
TI  - Cutting edge: telomerase activation in human T lymphocytes does not require
      increase in telomerase reverse transcriptase (hTERT) protein but is associated
      with hTERT phosphorylation and nuclear translocation.
AB  - Capacity for cellular replication is critically important for lymphocyte function
      and can be regulated by telomerase-dependent maintenance of telomere length. In
      contrast to most normal human somatic cells that do not express telomerase due to
      the failure to transcribe telomerase reverse transcriptase (hTERT), lymphocytes
      express telomerase in a highly regulated fashion yet constitutively transcribe
      hTERT during development and activation. Here, we report that hTERT protein is
      present in both thymocytes and blood T cells at equivalent levels despite their
      substantial differences in telomerase activity, and that induction of telomerase
      activity in resting CD4(+) T cells is not dependent on net hTERT protein
      increase. Moreover, hTERT is phosphorylated and translocated from cytoplasm to
      nucleus during CD4(+) T cell activation. Thus, human T lymphocytes regulate
      telomerase function through novel events independent of hTERT protein levels, and
      hTERT phosphorylation and nuclear translocation may play a role in regulation of
      telomerase function in lymphocytes.

PMID- 11290758
TI  - Cutting edge: the Wiskott-Aldrich syndrome protein is required for efficient
      phagocytosis of apoptotic cells.
AB  - Phagocytosis of apoptotic cells by macrophages and dendritic cells is necessary
      for clearance of proinflammatory debris and for presentation of viral, tumor, and
      self Ags. While a number of receptors involved in the cognate recognition of
      apoptotic cells by phagocytes have been identified, the signaling events that
      result in internalization remain poorly understood. Here we demonstrate that
      clearance of apoptotic cells is accompanied by recruitment of the Wiskott-Aldrich
      syndrome (WAS) protein to the phagocytic cup and that it's absence results in
      delayed phagocytosis both in vitro and in vivo. Therefore, we propose that WAS
      protein plays an important and nonredundant role in the safe removal of apoptotic
      cells and that deficiency contributes significantly to the immune dysregulation
      of WAS. The efficiency of apoptotic cell clearance may be a key determinant in
      the suppression of tissue inflammation and prevention of autoimmunity.

PMID- 11290759
TI  - A CCR5-dependent novel mechanism for type 1 HIV gp120 induced loss of macrophage
      cell surface CD4.
AB  - Type 1 HIV gp120 is especially effective in disrupting immune cell function
      because it is able to cause dysregulation of both infected and uninfected cells.
      We report a novel CCR5-dependent mechanism of gp120-induced CD4 loss from
      macrophages. An M-tropic gp120, using CCR5, is able to induce 70% loss of cell
      surface CD4 from macrophages within an hour. This cell surface CD4 loss is more
      substantial and rapid than the 20% loss observed with T-tropic gp120(IIIB) by 3
      h. The rapid and substantial CD4 loss induced by M-tropic gp120 is not observed
      on macrophages homozygous for the ccr5Delta32 mutation, which fail to express
      cell surface CCR5. We have used confocal imaging to show that gp120 and CD4 are
      internalized together by a process resembling receptor-mediated endocytosis, and
      that both proteins enter HLA-DR containing compartments of the macrophage. We
      have also shown by semiquantitative RT-PCR that, in response to CD4 loss from the
      cell surface, mRNA for CD4 is up-regulated and the intracellular pool of CD4
      increases. CCR5 mRNA levels are also increased. It is proposed that
      internalization of self and viral protein and increased pools of intracellular
      CD4 could modulate Ag presentation efficiencies and have implications for the
      induction and maintenance of both productive immune responses and self-tolerance.

PMID- 11290760
TI  - The role of dendritic cells, B cells, and M cells in gut-oriented immune
      responses.
AB  - Although induction of T cell responses to fed Ag (oral tolerance) is thought to
      happen within the organized lymphoid tissue of the gut, we found that mice
      lacking Peyer's patches, B cells, and the specialized Ag-handling M cells had no
      defect in the induction of T cell responses to fed Ag, whether assayed in vitro
      by T cell proliferation or cytokine production, or in vivo by delayed-type
      hypersensitivity or bystander suppression against mycobacterial Ags in CFA.
      Feeding of Ag had a major influence on dendritic cells from fed wild-type or muMT
      mice, such that these APCs were able to elicit a different class of response from
      naive T cells in vitro. These results suggest that systemic immune responses to
      soluble oral Ags do not require an organized gut-associated lymphoid tissue but
      are most likely induced by gut-conditioned dendritic cells that function both to
      initiate the gut-oriented response and to impart the characteristic features that
      discriminate it from responses induced parenterally.

PMID- 11290761
TI  - Transgenic expression of IL-10 in T cells facilitates development of experimental
      myasthenia gravis.
AB  - Ab to the acetylcholine receptor (AChR) cause experimental myasthenia gravis
      (EMG). Th1 cytokines facilitate EMG, whereas Th2 cytokines might be protective.
      IL-10 inhibits Th1 responses but facilitates B cell proliferation and Ig
      production. We examined the role of IL-10 in EMG by using wild-type (WT) C57BL/6
      mice and transgenic (TG) C57BL/6 mice that express IL-10 under control of the IL
      2 promoter. We immunized the mice with doses of AChR that cause EMG in WT mice or
      with low doses ineffective at causing EMG in WT mice. After low-dose AChR
      immunization, WT mice did not develop EMG and had very little anti-AChR serum Ab,
      which were mainly IgG1, whereas TG mice developed EMG and had higher levels of
      anti-AChR serum Ab, which were mainly IgG2, in addition to IgG1. At the higher
      doses, TG mice developed EMG earlier and more frequently than WT mice and had
      more serum anti-AChR Ab. Both strains had similar relative serum concentrations
      of anti-AChR IgG subclasses and IgG and complement at the muscle synapses. CD8(+)
      depleted splenocytes from all AChR-immunized mice proliferated in the presence of
      AChR and recognized a similar epitope repertoire. CD8(+)-depleted splenocytes
      from AChR-immunized TG mice stimulated in vitro with AChR secreted significantly
      more IL-10, but less of the prototypic Th1 cytokine IFN-gamma, than those from WT
      mice. They secreted comparable amounts of IL-4 and slightly but not significantly
      reduced amounts of IL-2. This suggests that TG mice had reduced activation of
      anti-Torpedo AChR Th1 cells, but increased anti-AChR Ab synthesis, that likely
      resulted from IL-10-mediated stimulation of anti-AChR B cells. Thus, EMG
      development is not strictly dependent on Th1 cell activity.

PMID- 11290762
TI  - Suppression of IgE responses in CD23-transgenic animals is due to expression of
      CD23 on nonlymphoid cells.
AB  - Serum IgE is suppressed in CD23-transgenic (Tg) mice where B cells and some T
      cells express high levels of CD23, suggesting that CD23 on B and T cells may
      cause this suppression. However, when Tg B lymphocytes were compared with
      controls in B cell proliferation and IgE synthesis assays, the two were
      indistinguishable. Similarly, studies of lymphokine production suggested that T
      cell function in the Tg animals was normal. However, adoptive transfer studies
      indicated that suppression was seen when normal lymphocytes were used to
      reconstitute Tg mice, whereas reconstitution of controls with Tg lymphocytes
      resulted in normal IgE responses, suggesting that critical CD23-bearing cells are
      irradiation-resistant, nonlymphoid cells. Follicular dendritic cells (FDC) are
      irradiation resistant, express surface CD23, and deliver iccosomal Ag to B cells,
      prompting us to reason that Tg FDC may be a critical cell. High levels of
      transgene expression were observed in germinal centers rich in FDC and B cells,
      and IgE production was inhibited when Tg FDCs were cultured with normal B cells.
      In short, suppressed IgE production in CD23-Tg mice appears to be associated with
      a population of radioresistant nonlymphoid cells. FDCs that interface with B
      cells in the germinal center are a candidate for explaining this CD23-mediated
      IgE suppression.

PMID- 11290763
TI  - Coregulation of CXC chemokine receptor and CD4 expression on T lymphocytes during
      allogeneic activation.
AB  - Upon activation, naive T cells alter their migratory patterns, acquiring the
      ability to move through peripheral tissues as well as the general lymphoid
      circulation. Although the mechanisms responsible for these alterations are not
      well understood, changes in chemokine receptor expression may play a critical
      role. To investigate these changes, the expression patterns of two chemokine
      receptors, CXCR3 and CXCR4, were compared on CD4(+) T cells following activation
      in the MLR. By day 9 of activation, expression of the inflammatory chemokine
      receptor CXCR3 was up-regulated, while expression of the homeostatic chemokine
      receptor CXCR4 was down-regulated. Alterations in receptor expression occurred
      almost exclusively on a subpopulation of T cells that expressed higher levels of
      CD4. These CD4(high) T cells demonstrated many characteristics of activated T
      cells and had undergone division in the MLR. By day 9 of culture, the majority of
      CXCR3(+) and CXCR4(-) cells had divided and had acquired an activated/memory
      phenotype (CD45RA(-) CD45RO(+) CD69(+) CD25(+)). The levels of transcripts for
      both CXCR3 and CXCR4 were increased upon allo-activation. The discrepancy between
      levels of CXCR4 mRNA and surface protein was not due to sequestration of the
      receptor in intracellular compartments, as CXCR4 was not detectable
      intracellularly. However, intracellular CXCR3 was readily detectable. Finally,
      cells from allogeneic cultures demonstrated enhanced migration toward IFN
      inducible T cell alpha chemoattractant and reduced migration toward stromal cell
      derived factor-1 compared with syngeneic controls, thus suggesting that the
      observed switch in receptor expression may at least partly contribute to the
      differential patterns of migration displayed by naive and memory T cells.

PMID- 11290764
TI  - Acute rejection in the absence of cognate recognition of allograft by T cells.
AB  - We studied the effects of the indirect pathway of allograft recognition using T
      cells from TCR transgenic Marilyn mice, which recognize the male Ag H-Y in an I
      A(b)-restricted fashion. The T cells are not alloreactive to the H-2(k)
      haplotype, because they are not activated when adoptively transferred into
      recombinase-activating gene-2(-/-) common gamma-chain(-/-) double-mutant H-2(k)
      male or female mice. However, skin from H-2(k) males, but not from H-2(k)
      females, is acutely rejected by recombinase-activating gene-2(-/-) transgenic
      female recipients. In vitro, Marylin spleen cells primed by H-2(k) skin grafting
      proliferated and secreted both IL-4 and IFN-gamma in response to H-2(k) male
      stimulators. However, the removal of H-2(b) APC from the responding population
      abolished the response. Taken together, these results show that the indirect
      recognition that triggers rejection in this model is due to the recognition of H
      Y Ag shed from H-2(k) male allograft and presented by the recipient's own I-A(b)
      APC to transgenic T cells. This study demonstrates unequivocally the capacity of
      naive CD4(+) T cells to promote the rejection of allografts through mechanisms
      that involve indirect destruction of grafted tissues.

PMID- 11290765
TI  - Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch
      dendritic cells.
AB  - We have recently demonstrated the presence of three populations of dendritic
      cells (DC) in the murine Peyer's patch. CD11b(+)/CD8alpha(-) (myeloid) DCs are
      localized in the subepithelial dome, CD11b(-)/CD8alpha(+) (lymphoid) DCs in the
      interfollicular regions, and CD11b(-)/CD8alpha(-) (double-negative; DN) DCs at
      both sites. We now describe the presence of a novel population of intraepithelial
      DN DCs within the follicle-associated epithelium and demonstrate a predominance
      of DN DCs only in mucosal lymphoid tissues. Furthermore, we demonstrate that all
      DC subpopulations maintain their surface phenotype upon maturation in vitro, and
      secrete a distinct pattern of cytokines upon exposure to T cell and microbial
      stimuli. Only myeloid DCs from the PP produce high levels of IL-10 upon
      stimulation with soluble CD40 ligand(-) trimer, or Staphylococcus aureus and IFN
      gamma. In contrast, lymphoid and DN, but not myeloid DCs, produce IL-12p70
      following microbial stimulation, whereas no DC subset produces IL-12p70 in
      response to CD40 ligand trimer. Finally, we show that myeloid DCs from the PP are
      particularly capable of priming naive T cells to secrete high levels of IL-4 and
      IL-10, when compared with those from nonmucosal sites, while lymphoid and DN DCs
      from all tissues prime for IFN-gamma production. These findings thus suggest that
      DC subsets within mucosal tissues have unique immune inductive capacities.

PMID- 11290766
TI  - Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to
      death receptor 4.
AB  - To explore an approach for death receptor targeting in cancer, we developed
      murine mAbs to human death receptor 4 (DR4). The mAb 4H6 (IgG1) competed with
      Apo2L/TNF-related apoptosis-inducing ligand (DR4's ligand) for binding to DR4,
      whereas mAb 4G7 (IgG2a) did not. In vitro, both mAbs showed minimal intrinsic
      apoptosis-inducing activity, but each triggered potent apoptosis upon cross
      linking. In a colon tumor nude mouse model in vivo, mAb 4H6 treatment without
      addition of exogenous linkers induced apoptosis in tumor cells and caused
      complete tumor regression, whereas mAb 4G7 partially inhibited tumor growth. An
      IgG2a isotype switch variant of mAb 4H6 was much less effective in vivo than the
      parent IgG1-4H6, despite similar binding affinities to DR4. The same conclusion
      was obtained by comparing other IgG1 and IgG2 mAbs to DR4 for their anti-tumor
      activities in vivo. Thus, the isotype of anti-DR4 mAb may be more important than
      DR4 binding affinity for tumor elimination in vivo. Anti-DR4 mAbs of the IgG1
      isotype may provide a useful tool for investigating the therapeutic potential of
      death receptor targeting in cancer.

PMID- 11290767
TI  - Antibody binding to a conformation-dependent epitope induces L-selectin
      association with the detergent-resistant cytoskeleton.
AB  - L-Selectin mediates leukocyte rolling on endothelium and immobilized leukocytes.
      Its regulation has been the subject of much study, and the conformation of the
      molecule may play an important role in its function. Here we report that a
      conformational change in L-selectin, induced by an anti-lectin domain mAb (LAM1
      116) and recognized by another mAb directed to a conserved epitope on L-selectin
      (EL-246), predisposed L-selectin to cytoskeletal association. This effect was due
      to direct binding of the mAb, not to overt signaling events, and was specific to
      LAM1-116. Nineteen other anti-L-selectin mAbs directed against the lectin,
      epidermal growth factor, or short consensus repeat domains lacked this activity.
      The induced conformational change occurred at 37 degrees C, at 4 degrees C, in
      the presence of sodium azide and tyrosine kinase inhibitors herbimycin A and
      genistein, and with soluble detergent-extracted L-selectin. In the presence of
      LAM1-116, EL-246 induced cytoskeletal association of L-selectin in the absence of
      Ab cross-linking as visualized by L-selectin staining after low dose detergent
      treatment of the cells. We propose that the conformational change described
      herein regulates L-selectin-mediated events by exposing a high avidity binding
      site that, when engaged, triggers association of L-selectin with the
      cytoskeleton, which may lead to stronger tethers with physiological ligands.

PMID- 11290768
TI  - CD80 costimulation is required for Th2 cell cytokine production but not for
      antigen-specific accumulation and migration into the lung.
AB  - The CD28 ligands CD80 and CD86 are expressed on APC, and both provide
      costimulatory function. However, the reason for the expression of two separate
      CD28 ligands remains unclear. We have previously shown that blockade of CD80
      costimulation by Y100F-Ig, a CTL-associated Ag-4 (CTLA4)-Ig mutant that does not
      bind CD86, inhibits the development of lung inflammatory immune responses, but
      does not affect blood eosinophilia or Ab production. Each of those responses was
      inhibited by treatment with CTLA4-Ig, which binds both CD80 and CD86. To clarify
      the mechanism underlying these observations we have developed a model of lung
      inflammation using adoptively transferred CD4(+) T cells expressing a
      Valpha11(+)Vbeta3(+) transgenic TCR specific for I-E(k) and moth cytochrome c.
      Treatment with Y100F-Ig inhibited the induction of lung eosinophilia in
      adoptively transferred mice. However, Y100F-Ig did not detectably affect the
      accumulation of Ag-specific T cells at the site of peptide deposit or in the
      draining lymphoid tissues. Acquisition of an activated phenotype and expression
      of adhesion molecules required for migration into the lung were modestly
      affected. Importantly, treatment with Y100F-Ig diminished the ability of T cells
      to produce the cytokines IL-4 and IL-5 following intranasal challenge with Ag.
      All the responses examined were severely inhibited by treatment with CTLA4-Ig. We
      conclude that T cells require CD80 costimulation for the optimal production of IL
      5 following intranasal administration of Ag. Decreased IL-5 production is the
      most likely explanation for the diminished airway eosinophilia observed.

PMID- 11290769
TI  - IL-12 alone and in synergy with IL-18 inhibits osteoclast formation in vitro.
AB  - IL-12, like IL-18, was shown to potently inhibit osteoclast formation in cultures
      of cocultures of murine osteoblast and spleen cells, as well as in adult spleen
      cells treated with M-CSF and receptor activator of NF-kappaB ligand (RANKL).
      Neither IL-12 nor IL-18 was able to inhibit RANKL-induced osteoclast formation in
      cultured RAW264.7 cells, demonstrating that IL-12, like IL-18, was unable to act
      directly on osteoclastic precursors. IL-12, like IL-18, was found to act by T
      cells, since depletion of T cells from the adult spleen cell cultures ablated the
      inhibitory action of IL-12 and addition of either CD4 or CD8 T cells from C57BL/6
      mice to RANKL-stimulated RAW264.7 cultures permitted IL-12 or IL-18 to be
      inhibitory. Additionally, IL-12 was still able to inhibit osteoclast formation in
      cocultures with osteoblasts and spleen cells from either GM-CSF R(-/-) mice or
      IFN-gamma R(-/-) mice, indicating that neither GM-CSF nor IFN-gamma was mediating
      osteoclast inhibition in these cultures. Combined, IL-18 and IL-12
      synergistically inhibited osteoclast formation at concentrations 20- to 1000-fold
      less, respectively, than when added individually. A candidate inhibitor could not
      be demonstrated using neutralizing Abs to IL-4, IL-10, or IL-13 or from mRNA
      expression profiles among known cytokine inhibitors of osteoclastogenesis in
      response to IL-12 and IL-18 treatment, although the unknown inhibitory molecule
      was determined to be secreted from T cells.

PMID- 11290770
TI  - Modulation of inhaled antigen-induced IgE tolerance by ongoing Th2 responses in
      the lung.
AB  - The normal response to inhaled Ag is the absence of Ag-specific IgE and cytokine
      production to later Ag challenges. Although the mechanism of this aerosol-induced
      IgE tolerance is not completely understood, it may prevent sensitization to
      inhaled Ags, which could otherwise lead to allergy and asthma. We examined the
      consequences of ongoing Th1 and Th2 responses in the lungs of mice during OVA
      inhalation to mimic conditions that may subvert tolerance and lead to
      sensitization. We found that concurrent, secondary Th2 lung responses to keyhole
      limpet hemocyanin or primary responses to Nippostrongylus larvae or Asperigillus
      fumagatus extract prevented establishment of IgE tolerance to aerosolized OVA.
      Intranasal rIL-4 given before OVA aerosolization also prevented establishment of
      tolerance, whereas concurrent Th1 responses to influenza virus or Mycobacterium
      bovis bacillus Calmette-Guerin had no effect. However, once established, aerosol
      tolerance to OVA could not be completely broken by OVA rechallenge concurrent
      with a secondary Th2 response to keyhole limpet hemocyanin or A. fumagatus
      extract, or by intranasal rIL-4. These data suggest that the immune status of the
      lung of an individual may profoundly influence the initial response to inhaled
      Ag, and that aerosol-induced IgE tolerance may not be appropriately established
      in individuals undergoing concurrent, Th2-mediated responses to Ags or pathogens.

PMID- 11290771
TI  - CD99 signals caspase-independent T cell death.
AB  - Death signaling by Fas and TNF receptors plays a major role in the control of
      activated mature T cells. However, the nature of the death receptors, which may
      be used by the immune system to control T cells that have not acquired
      susceptibility to Fas ligand or TNF, is not established. In this study, we
      demonstrate that engagement of distinct epitopes on CD99 rapidly induces T cell
      death by a novel caspase-independent pathway. A new mAb to these CD99 epitopes,
      Ad20, induces programmed cell death of transformed T cells as determined by
      morphological changes, phosphatidylserine exposure on the cell surface, and
      uptake of propidium iodide. In general, ligation of CD99 induced kinetically
      faster and more profound death responses as compared with the impact of anti-Fas
      and TNF-related apoptosis-inducing ligand (TRAIL). Ad20-induced programmed cell
      death was observed with seven of eight T cell lines examined, and notably, only
      two of these were distinctly responsive to anti-Fas and TRAIL. CD99-mediated
      death signaling proceeded independently of functional CD3, CD4, CD45, and
      p56(lck), revealed distinctions from CD47-mediated T cell death responses, and
      was not influenced by interference with CD47 signaling. In contrast to the effect
      on transformed T cell lines, Ad20-induced death responses were not observed with
      normal peripheral T cells. Thus, our data suggest that CD99 is linked to a novel
      death pathway that may have biologic relevance in control of early T cells.

PMID- 11290772
TI  - ICOS costimulation requires IL-2 and can be prevented by CTLA-4 engagement.
AB  - We investigated the relationship between ICOS, CD28, CTLA-4, and IL-2 to gain a
      better understanding of this family of costimulatory receptors in the immune
      response. Using magnetic beads coated with anti-CD3 and varying amounts of anti
      ICOS and anti-CTLA-4 Abs, we show that CTLA-4 ligation blocks ICOS costimulation.
      In addition to inhibiting cellular proliferation, CTLA-4 engagement prevented
      ICOS-costimulated T cells from producing IL-4, IL-10, and IL-13. Both an indirect
      and direct mechanism of CTLA-4's actions were examined. First, CTLA-4 engagement
      on resting cells was found to indirectly block ICOS costimulation by interferring
      with the signals needed to induce ICOS cell surface expression. Second, on
      preactivated cells that had high levels of ICOS expression, CTLA-4 ligation
      blocked the ICOS-mediated induction of IL-4, IL-10, and IL-13, suggesting an
      interference with downstream signaling pathways. The addition of IL-2 not only
      overcame both mechanisms, but also greatly augmented the level of cellular
      activation suggesting synergy between ICOS and IL-2 signaling. This cooperation
      between ICOS and IL-2 signaling was explored further by showing that the minimum
      level of IL-2 produced by ICOS costimulation was required for T cell
      proliferation. Finally, exogenous IL-2 was required for sustained growth of ICOS
      costimulated T cells. These results indicate that stringent control of ICOS
      costimulation is maintained initially by CTLA-4 engagement and later by a
      requirement for exogenous IL-2.

PMID- 11290773
TI  - NF-kappa B RelA (p65) is essential for TNF-alpha-induced fas expression but
      dispensable for both TCR-induced expression and activation-induced cell death.
AB  - The Fas death receptor plays a key role in the killing of target cells by NK
      cells and CTLs and in activation-induced cell death of mature T lymphocytes.
      These cytotoxic pathways are dependent on induction of Fas expression by
      cytokines such as TNF-alpha and IFN-gamma or by signals generated after TCR
      engagement. Although much of our knowledge of the Fas death pathway has been
      generated from murine studies, little is known about regulatory mechanisms
      important for murine Fas expression. To this end, we have molecularly cloned a
      region of the murine Fas promoter that is responsible for mediating TNF-alpha and
      PMA/PHA-induced expression. We demonstrate here that induction of Fas expression
      by both stimuli is critically dependent on two sites that associate with RelA
      containing NF-kappaB complexes. To determine whether RelA and/or other NF-kappaB
      subunits are also important for regulating Fas expression in primary T cells, we
      used CD4 T cells from RelA(-/-), c-Rel(-/-), and p50(-/-) mice. Although
      proliferative responses were significantly impaired, expression of Fas and
      activation-induced cell death was unaffected in T cells obtained from these
      different mice. Importantly, we show that unlike fibroblasts, which consist
      primarily of RelA-containing NF-kappaB complexes, T cells have high levels of
      both RelA and c-Rel complexes, suggesting that Fas expression in T cells may be
      dependent on redundant functions of these NF-kappaB subunits.

PMID- 11290774
TI  - Migration and maturation of human colonic dendritic cells.
AB  - Dendritic cells (DC) in the colon may regulate intestinal immunity but remain
      poorly characterized. In this study a CD11c(+)HLA-DR(+)lin(-) (CD3(-)CD14(-)CD16(
      )CD19(-)CD34(-)) population has been identified by flow cytometry in cells
      obtained by rapid collagenase digestion of human colonic and rectal biopsies.
      These day 0 (d0) CD11c(+)HLA-DR(+)lin(-) cells comprised approximately 0.6% of
      the mononuclear cells obtained from the lamina propria, were endocytically
      active, and had the phenotype of immature DC; they were CD40(+) and expressed low
      levels of CD83 and CD86, but little or no CD80 or CD25. Similar d0 DC populations
      were isolated from the colonic mucosa of healthy controls and from both inflamed
      and noninflamed tissue from patients with Crohn's disease. The lamina propria
      also contained a population of cells capable of migrating out of biopsies during
      an overnight culture and differentiating into mature DC with lower levels of
      endocytic activity and high cell surface expression of CD40, CD80, CD86, CD83,
      and CD25. This mature DC population was a potent stimulator of an allogeneic
      mixed leukocyte (MLR). Overnight culture of cells isolated by enzymatic digestion
      on d0 yielded DC with a phenotype intermediate between that of the d0 cells and
      that of the cells migrating out overnight. Overnight culture of colonic cells in
      which DC and HLA-DR(+)lin(+) cells were differentially labeled with FITC-dextran
      suggested that some of the maturing DC might differentiate from HLA-DR(+)lin(+)
      progenitors. This study presents the first analysis of the phenotype,
      maturational status, and migratory activity of human gut DC.

PMID- 11290775
TI  - Adjuvanticity of alpha 2-macroglobulin, an independent ligand for the heat shock
      protein receptor CD91.
AB  - We recently have identified CD91 as a receptor for the heat shock protein gp96.
      CD91 was identified initially as a receptor for alpha(2)-macroglobulin
      (alpha(2)M). Gp96 and alpha(2)M are both ligands for CD91. Because gp96
      chaperoned peptides can prime CD8(+) T cell responses and are re-presented by
      APCs, we tested alpha(2)M for similar properties. Our studies show that alpha(2)M
      binds peptides in vitro and that the peptides, chaperoned by alpha(2)M,
      efficiently prime peptide-specific CD8(+) T cell responses in mice immunized with
      alpha(2)M-peptide complexes. Furthermore, peptides chaperoned by alpha(2)M, like
      those chaperoned by gp96, can be re-presented by CD91(+) APCs on their MHC I
      molecules. These studies demonstrate that alpha(2)M molecules, like the heat
      shock protein molecules, are T cell adjuvants that can channel exogenous Ags into
      the endogenous pathway of Ag presentaion. The remarkable similarities between an
      intracellular chaperone and an extracellular serum chaperone may have interesting
      physiological ramifications.

PMID- 11290776
TI  - The activity of immunoregulatory T cells mediating active tolerance is
      potentiated in nonobese diabetic mice by an IL-4-based retroviral gene therapy.
AB  - Splenocytes from nonobese diabetic mice overexpressing murine IL (mIL)-4 upon
      recombinant retrovirus infection lose their capacity to transfer diabetes to
      nonobese diabetic-scid recipients. Diabetes appeared in 0-20% of mice injected
      with mIL-4-transduced cells vs 80-100% of controls injected with beta
      galactosidase-transduced cells. Protected mice showed a majority of islets (60%)
      presenting with noninvasive peri-insulitis at variance with beta-galactosidase
      controls that exhibited invasive/destructive insulitis. Importantly, in all
      recipients, the transduced proteins were detected within islet infiltrates.
      Infiltrating lymphocytes from recipients of mIL-4-transduced cells produced high
      levels of mIL-4, as assessed by ELISA. In recipients of beta-galactosidase
      transduced cells, approximately 60% of TCRalphabeta(+) islet-infiltrating cells
      expressed beta-galactosidase, as assessed by flow cytometry. The protection from
      disease transfer is due to a direct effect of mIL-4 gene therapy on
      immunoregulatory T cells rather than on diabetogenic cells. mIL-4-transduced
      purified CD62L(-) effector cells or transgenic BDC2.5 diabetogenic T cells still
      transferred disease efficiently. Conversely, mIL-4 transduction up-regulated the
      capacity of purified immunoregulatory CD62L(+) cells to inhibit disease transfer.
      These data open new perspectives for gene therapy in insulin-dependent diabetes
      using T cells devoid of any intrinsic diabetogenic potential.

PMID- 11290777
TI  - Impaired Fas signaling pathway is involved in defective T cell apoptosis in
      autoimmune murine arthritis.
AB  - Proteoglycan (PG)-induced arthritis (PGIA) is a novel autoimmune murine model for
      rheumatoid arthritis induced by immunization with cartilage PG in susceptible
      BALB/c mice. In this model, hyperproliferation of peripheral CD4(+) T cells has
      been observed in vitro with Ag stimulation, suggesting the breakdown of
      peripheral tolerance. Activation-induced cell death (AICD) is a major mechanism
      for peripheral T cell tolerance. A defect in AICD may result in autoimmunity. We
      report in this study that although CD4(+) T cells from both BALB/c and B6 mice,
      identically immunized with human cartilage PG or OVA, express equally high levels
      of Fas at the cell surface, CD4(+) T cells from human cartilage PG-immunized
      BALB/c mice, which develop arthritis, fail to undergo AICD. This defect in AICD
      in PGIA may lead to the accumulation of autoreactive Th1 cells in the periphery.
      The impaired AICD in PGIA might be ascribed to an aberrant expression of Fas-like
      IL-1beta-converting enzyme-inhibitory protein, which precludes caspase-8
      activation at the death-inducing signaling complex, and subsequently suppresses
      the caspase cascade initiated by Fas-Fas ligand interaction. Moreover, this
      aberrant expression of Fas-like IL-1beta-converting enzyme-inhibitory protein may
      also mediate TCR-induced hyperproliferation of CD4(+) T cells from arthritic
      BALB/c mice. Our data provide the first insight into the molecular mechanism(s)
      of defective AICD in autoimmune arthritis.

PMID- 11290778
TI  - An HLA-DRB1-derived peptide associated with protection against rheumatoid
      arthritis is naturally processed by human APCs.
AB  - Predisposition to rheumatoid arthritis (RA) is thought to be associated with HLA
      DR1, -DR4, and -DR10. However, many epidemiological observations are better
      explained by a model in which the DQ alleles that are linked to these DR alleles,
      i.e., DQ5, DQ7, and DQ8, predispose to RA, while certain DR alleles have a
      dominant protective effect. All protective DRB1 alleles, e.g., *0402, *1301, and
      *1302, encode a unique motif, (70)DERAA(74). The protection may be explained by
      the presentation of DRB1-derived peptides by DQ to immunoregulatory T cells,
      because it was demonstrated in various autoimmune disease models that T cell
      responses to certain self-Ags can be involved in disease suppression. The aim of
      this study was to analyze whether peptides carrying the DERAA motif are naturally
      processed by human APC and presented in the context of the RA-predisposing DQ.
      Using a synthetic peptide carrying the DRB1*0402-derived sequence
      (65)KDILEDERAAVDTYC(79), we generated DERAA peptide-specific DQ-restricted T cell
      clones (TCC) from a DQ8 homozygous individual carrying DERAA-negative DR4
      alleles. By analyzing the proliferation of these TCC, we demonstrated natural
      processing and presentation of the DERAA sequence by the APC of all the
      individuals (n = 12) carrying a DERAA-positive DRB1 allele and either DQ8 or the
      DQ8-related DQ7. Using a panel of truncated synthetic peptides, we identified the
      sequence (67)(I)LEDERAAVD(TY)(78) as the minimal determinant for binding to DQ8
      and for recognition by the TCC. These findings support a model in which self-MHC
      derived peptide can modulate predisposition to autoimmune disease in humans.

PMID- 11290779
TI  - Activating Ly-49 NK receptors: central role in cytokine and chemokine production.
AB  - In an attempt to understand potential novel functions of receptors in vivo, we
      evaluated gene expression after cross-linking the activating Ly-49D mouse NK
      receptor. Gene expression was evaluated using a mouse GEM 2 microarray chip
      (Incyte Genomics, St. Louis, MO). Each chip displays a total of 8734 elements.
      The strongly induced genes fell into two categories: 1) soluble factors and 2)
      apoptotic genes. The majority of the strongly induced mRNAs as analyzed by
      microarray hybridization were chemokine genes. RNase protection assays and
      chemokine protein production analysis validated the microarray results, as cross
      linking the Ly-49D mouse NK receptor induced high levels of IFN-gamma,
      lymphotactin, macrophage-inflammatory protein (MIP)1alpha, and MIP1beta. This
      gene expression was specific because other chemokines were not induced by anti-Ly
      49D receptors. In addition, a series of pharmacological inhibitors were used to
      identify the key signaling pathways involved in the cellular response. The
      primary Ly-49D signaling for IFN-gamma production is predominantly mediated
      through Src kinase pathways involving membrane proximal events, whereas MIP1alpha
      and MIP1beta gene induction is more complex and may involve multiple biochemical
      pathways. Thus, we conclude that a primary role for the activating NK receptors
      in vivo may be to trigger soluble factor production and regulation of the immune
      response. This would place NK cells and their activating Ly-49 receptors as
      important initiators of microbial immunity and key elements of the innate immune
      system.

PMID- 11290780
TI  - Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+
      dendritic cells.
AB  - Human plasmacytoid precursor dendritic cells (ppDC) are a major source of type I
      IFN upon exposure to virus and bacteria, yet the stimulus causing their
      maturation into DCs is unknown. After PBMC activation with immunostimulatory
      bacterial DNA sequences (CpG-DNA) we found that ppDC are the primary source of
      IFN-alpha. In fact, either CpG-DNA or dsRNA (poly(I:C)) induced IFN-alpha from
      purified ppDC. Surprisingly, only CpG-DNA triggered purified ppDC survival,
      maturation, and production of TNF, GM-CSF, IL-6, and IL-8, but not IL-10 or IL
      12. Known DC activators such as CD40 ligation triggered ppDC maturation, but only
      IL-8 production, while bacterial LPS was negative for all activation criteria. An
      additional finding was that only CpG-DNA could counteract IL-4-induced apoptosis
      in ppDC. Therefore, CpG-DNA represents a pathogen-associated molecular pattern
      for ppDC. In contrast to these finding, CpG-DNA, like LPS, caused TNF, IL-6, and
      IL-12 release from PBMC and purified monocytes; however, differentiation of
      monocytes into DCs with GM-CSF and IL-4 unexpectedly resulted in refractoriness
      to CpG-DNA, but not LPS. Taken together, these results suggest that within a DC
      subset a multiplicity of responses can be generated by distinct environmental
      stimuli and that responses to a given stimulus may be dissimilar between DC
      subsets.

PMID- 11290781
TI  - Murine dendritic cells derived from myeloid progenitors of the thymus are unable
      to produce bioactive IL-12p70.
AB  - Dendritic cells (DC) are present at low density in the thymus where they mediate
      negative selection of self-reactive thymocytes. Previous reports suggest that
      thymic DC (TDC) are a single population of lymphoid-related DC. In this study, we
      documented the presence in the adult mouse thymus of an additional population of
      TDC exhibiting a myeloid phenotype (CD11c(+) CD8alpha(-) CD11b(+)). This
      population, which can be purified, represented approximately 20% of the total TDC
      and differs from the population of lymphoid TDC (CD11c(+) CD8(+) CD11b(-)) by its
      incapacity to produce IL-12p70 under double stimulation by LPS and anti-CD40.
      Furthermore, using an original culture system allowing expansion of DC from
      myeloid progenitors, we demonstrated that DC exhibiting a similar myeloid
      phenotype can be derived from a common DC/macrophage progenitor resident in the
      adult mouse thymus. We found that, in contrast with myeloid splenic DC expanded
      in the same conditions, these cultured TDC were unable to produce IL-12p70 under
      double stimulation by LPS and anti-CD40 or LPS and IFN-gamma. Thus, our results
      suggest that 1) adult mouse thymus contains at least two phenotypically and
      functionally distinct populations of DC; and 2) cultured myeloid DC derived from
      thymus and spleen differ by their ability to produce IL-12p70. The mechanisms
      underlying the differences in IL-12-secreting capacities of the cultured splenic
      and thymic DC are under current investigation.

PMID- 11290782
TI  - HLA-G2, -G3, and -G4 isoforms expressed as nonmature cell surface glycoproteins
      inhibit NK and antigen-specific CTL cytolysis.
AB  - HLA-G is a nonclassical MHC class I molecule that plays a major role in maternal
      fetal tolerance. Four membrane-bound (HLA-G1 to -G4) and two soluble (HLA-G5, and
      -G6) proteins are generated by alternative splicing. Only HLA-G1 has been
      extensively studied in terms of both expression and function. We provide evidence
      here that HLA-G2, -G3, and -G4 truncated isoforms reach the cell surface of
      transfected cells, as endoglycosidase H-sensitive glycoproteins, after a 2-h
      chase period. Moreover, cytotoxicity experiments show that these transfected
      cells are protected from the lytic activity of both innate (NK cells) and
      acquired (CTL) effectors. These findings highlight the immunomodulatory role that
      HLA-G2, -G3, and -G4 proteins will assume during physiologic or pathologic
      processes in which HLA-G1 expression is altered.

PMID- 11290783
TI  - CXCR-4 desensitization is associated with tissue localization of hemopoietic
      progenitor cells.
AB  - The chemokine stroma-derived factor (SDF)-1, and its receptor, CXCR-4, have been
      shown to be essential for the translocation of hemopoietic stem cells from the
      fetal liver to the bone marrow (BM). We hypothesized that if CXCR-4 plays a
      crucial role in the localization of human hemopoiesis, stem cells from distinct
      tissue sources should demonstrate distinct CXCR-4 expression or signaling
      profiles. CD34(+) cells from BM were compared with blood: either mobilized
      peripheral blood or umbilical cord blood. Unexpectedly, significantly higher
      levels of CXCR-4 surface expression on CD34(+) cells from blood sources,
      mobilized peripheral blood, or cord blood were observed compared with BM (p =
      0.0005 and p = 0.002, respectively). However, despite lower levels of CXCR-4,
      responsiveness of the cells to SDF-1 as measured by either calcium flux or
      transmigration was proportionally greatest in cells derived from BM. Further,
      internalization of CXCR-4 in response to ligand, associated with receptor
      desensitization, was significantly lower on BM-derived cells. Therefore,
      preserved chemokine receptor signaling was highly associated with marrow rather
      than blood localization. To test the functional effects of perturbing CXCR-4
      signaling, adult mice were exposed to the methionine-SDF-1beta analog that
      induces prolonged down-regulation/desensitization of CXCR-4 and observed
      mobilization of Lin(-), Sca-1(+), Thy-1(low), and c-kit(+) hemopoietic progenitor
      cells to the peripheral blood with a >30-fold increase compared with PBS control
      (p = 0.0007 day 1 and p = 0.004 day 2). These data demonstrate that CXCR-4
      expression and function can be dissociated in progenitor cells and that
      desensitization of CXCR-4 induces stem cell entry into the circulation.

PMID- 11290784
TI  - Class I MHC-binding characteristics of the 129/J Ly49 repertoire.
AB  - The Ly49 family of NK cell receptors and its MHC-binding characteristics have
      only been well characterized in C57BL/6 (B6) mice. Previous studies have shown
      that 129/J mice express unique Ly49 genes that are not found in the B6 strain.
      Screening of a 129/J cDNA library led to the discovery of 10 distinct full-length
      Ly49-related coding sequences (Ly49e, g, i, o, p, r, s, t, u, and v). Although
      129/J mice share identical class I MHC (K(b) and D(b)) transcripts with B6 mice,
      only one Ly49 is identical in the two strains (Ly49E). In addition to the
      previously characterized Ly49P, two new activating Ly49 proteins were discovered,
      Ly49R and U. The MHC specificity of the total 129/J Ly49 repertoire was evaluated
      with soluble class I MHC tetramers and found to be distinct compared with the B6
      Ly49 repertoire. Ly49V bound to many types of class I MHC, suggesting that
      Ly49V(+) NK cells may monitor host cells for a global down-regulation in MHC
      levels. An activating receptor, Ly49R, was shown to bind soluble class I
      molecules to a moderate degree, a result not previously observed for other
      activating Ly49 proteins. Furthermore, tetramer-binding results were confirmed
      functionally with cytotoxicity assays using sorted 129/J NK cells. This study
      shows that the Ly49 repertoire and its MHC-binding characteristics can be very
      different among inbred mouse strains. Ly49 divergence should be considered when
      using 129-derived embryonic stem cells for the production of gene-targeted mice,
      especially when an immune or NK-derived phenotype is under scrutiny.

PMID- 11290785
TI  - Opposite ability of pre-TCR and alpha beta TCR to induce apoptosis.
AB  - In early CD4(-)CD8(-) pro-thymocytes, signaling through the pre-TCR is crucial
      for survival and differentiation into CD4(+)CD8(+) cells. At this more mature
      stage, interactions between alphabetaTCR and self-Ag/MHC complexes in turn lead
      either to cell survival and differentiation (positive selection) or to cell death
      (negative selection). Intrinsic differences must therefore exist between pre-TCR
      signals in CD4(-)CD8(-) thymocytes and alphabetaTCR signals in CD4(+)CD8(+)
      cells, since only the latter can mediate a death signal. In this work, we
      directly compared the capability of pre-TCR and alphabetaTCR to induce apoptosis
      in a CD4(-)CD8(-) thymoma cell line following receptor cross-linking with mAbs.
      Cross-linking of alphabetaTCR triggered high levels of programmed cell death,
      mimicking the negative selection signal usually induced in CD4(+)CD8(+)
      thymocytes. In contrast, pre-TCR was very inefficient at inducing apoptosis upon
      cross-linking, despite similar levels of surface receptor expression.
      Importantly, inefficient apoptosis induction by the pre-TCR did not result from
      its weak association with TCRzeta chain, since TCRs containing alpha-pTalpha
      chimeric chains, binding weakly to TCRzeta, were still able to induce apoptosis.
      Although similar tyrosine phosphorylation and calcium influx were induced after
      either pre-TCR or alphabetaTCR cross-linking, the two pathways diverged at the
      level of Fas ligand induction. Among putative transcription factors involved in
      Fas ligand mRNA induction, Nur77 and NFAT transcriptional activities were readily
      induced after alphabetaTCR, but not pre-TCR, stimulation. Together, these results
      support the view that the structure of the pre-TCR and alphabetaTCR directly
      influences their apoptosis-inducing capabilities by activating distinct signaling
      pathways.

PMID- 11290786
TI  - Increased transcription levels induce higher mutation rates in a hypermutating
      cell line.
AB  - Somatic hypermutation, in addition to V(D)J recombination, is the other major
      mechanism that generates the vast diversity of the Ab repertoire. Point mutations
      are introduced in the variable region of the Ig genes at a million-fold higher
      rate than in the rest of the genome. We have used a green fluorescent protein
      (GFP)-based reversion assay to determine the role of transcription in the
      mutation mechanism of the hypermutating cell line 18-81. A GFP transgene
      containing a premature stop codon is transcribed from the inducible tet-on
      operon. Using the inducible promoter enables us to study the mutability of the
      GFP transgene at different transcription levels. By analyzing stable
      transfectants of a hypermutating cell line with flow cytometry, the mutation rate
      at the premature stop codon can be measured by the appearance of GFP-positive
      revertant cells. Here we show that the mutation rate of the GFP transgene
      correlates with its transcription level. Increased transcription levels of the
      GFP transgene caused an increased point mutation rate at the premature stop
      codon. Treating a hypermutating transfection clone with trichostatin A, a
      specific inhibitor of histone deacetylase, caused an additional 2-fold increase
      in the mutation rate. Finally, using Northern blot analysis we show that the
      activation-induced cytidine deaminase, an essential trans-factor for the in vivo
      hypermutation mechanism, is transcribed in the hypermutating cell line 18-81.

PMID- 11290787
TI  - Identification of novel functional regions important for the activity of HOXB7 in
      mammalian cells.
AB  - Members of the HOX family of homeobox transcription factors play a role in
      pattern formation in diverse developmental systems. The clearly documented role
      of HOX genes in the proliferation and differentiation of primary hematopoietic
      cells and cell lines provides a convenient system to pursue a biochemical
      analysis of HOX gene function in mammalian cells. To explore the role of HOXB7 in
      myeloid hematopoiesis, a number of mutations and deletions in the gene were
      constructed that targeted sequences with known functions or in regions that had
      not been examined previously. The wild-type and mutant B7 constructs were
      introduced into the murine myelomonocytic cell line, 32D, and assayed for their
      effects on G-CSF-induced myeloid differentiation. Wild-type HOXB7 inhibited the
      differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide
      motif or the DNA-binding homeodomain, as well as internal deletions of the N
      terminal unique region, blocked this effect. Interestingly, mutations eliminating
      two target sites for casein kinase II, the glutamate-rich C terminus, or the
      first 14 amino acids of HOXB7, led to enhanced 32D differentiation. A model
      proposing a role for these regions of HOXB7 is presented.

PMID- 11290788
TI  - Interaction properties of human mannan-binding lectin (MBL)-associated serine
      proteases-1 and -2, MBL-associated protein 19, and MBL.
AB  - The mannan-binding lectin (MBL) activation pathway of complement plays an
      important role in the innate immune defense against pathogenic microorganisms. In
      human serum, two MBL-associated serine proteases (MASP-1, MASP-2) and MBL
      associated protein 19 (MAp19) were found to be associated with MBL. With a view
      to investigate the interaction properties of these proteins, human MASP-1, MASP
      2, MAp19, as well as the N-terminal complement subcomponents C1r/C1s, Uegf, and
      bone morphogenetic protein-1-epidermal growth factor (CUB-EGF) segments of MASP-1
      and MASP-2, were expressed in insect or human kidney cells, and MBL was isolated
      from human serum. Sedimentation velocity analysis indicated that the MASP-1 and
      MASP-2 CUB-EGF segments and the homologous protein MAp19 all behaved as
      homodimers (2.8-3.2 S) in the presence of Ca(2+). Although the latter two dimers
      were not dissociated by EDTA, their physical properties were affected. In
      contrast, the MASP-1 CUB-EGF homodimer was not sensitive to EDTA. The three
      proteins and full-length MASP-1 and MASP-2 showed no interaction with each other
      as judged by gel filtration and surface plasmon resonance spectroscopy. Using the
      latter technique, MASP-1, MASP-2, their CUB-EGF segments, and MAp19 were each
      shown to bind to immobilized MBL, with K:(D) values of 0.8 nM (MASP-2), 1.4 nM
      (MASP-1), 13.0 nM (MAp19 and MASP-2 CUB-EGF), and 25.7 nM (MASP-1 CUB-EGF). The
      binding was Ca(2+)-dependent and fully sensitive to EDTA in all cases. These data
      indicate that MASP-1, MASP-2, and MAp19 each associate as homodimers, and
      individually form Ca(2+)-dependent complexes with MBL through the CUB-EGF pair of
      each protein. This suggests that distinct MBL/MASP complexes may be involved in
      the activation or regulation of the MBL pathway.

PMID- 11290789
TI  - Clustering of class I HLA oligomers with CD8 and TCR: three-dimensional models
      based on fluorescence resonance energy transfer and crystallographic data.
AB  - Fluorescence resonance energy transfer (FRET) data, in accordance with lateral
      mobility measurements, suggested the existence of class I HLA dimers and
      oligomers at the surface of live human cells, including the B lymphoblast cell
      line (JY) used in the present study. Intra- and intermolecular class I HLA
      epitope distances were measured on JY B cells by FRET using fluorophore
      conjugated Ag-binding fragments of mAbs W6/32 and L368 directed against
      structurally well-characterized heavy and light chain epitopes, respectively. Out
      of-plane location of these epitopes relative to the membrane-bound BODIPY-PC (2
      (4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3
      pentanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine) was also determined by
      FRET. Computer-simulated docking of crystallographic structures of class I HLA
      and epitope-specific Ag-binding fragments, with experimentally determined
      interepitope and epitope to cell surface distances as constraints, revealed
      several sterically allowed and FRET-compatible class I HLA dimeric and tetrameric
      arrangements. Extension of the tetrameric class I HLA model with interacting TCR
      and CD8 resulted in a model of a supramolecular cluster that may exist
      physiologically and serve as a functionally significant unit for a network of CD8
      HLA-I complexes providing enhanced signaling efficiency even at low MHC-peptide
      concentrations at the interface of effector and APCs.

PMID- 11290790
TI  - Relaxed DM requirements during class II peptide loading and CD4+ T cell
      maturation in BALB/c mice.
AB  - Current ideas about DM actions have been strongly influenced by studies of mutant
      strains expressing the H-2(b) haplotype. To evaluate DM contributions to class II
      activities in BALB/c mice, we generated a novel mutation at the DMa locus via
      embryonic stem cell technology. Unlike long-lived A(b)/class II-associated
      invariant chain-derived peptide (CLIP) complexes, mature A(d) and E(d) molecules
      are loosely occupied by class II-associated invariant chain-derived peptide and
      are SDS unstable. BALB/c DM mutants weakly express BP107 conformational epitopes
      and toxic shock syndrome toxin-1 superantigen-binding capabilities, consistent
      with partial occupancy by wild-type ligands. Near normal numbers of mature CD4(+)
      T cells fail to undergo superantigen-mediated negative selection, as judged by
      TCR Vbeta usage. Ag presentation assays reveal consistent differences for A(d)-
      and E(d)-restricted T cells. Indeed, the mutation leads to decreased peptide
      capture by A(d) molecules, and in striking contrast causes enhanced peptide
      loading by E(d) molecules. Thus, DM requirements differ for class II structural
      variants coexpressed under physiological conditions in the intact animal.

PMID- 11290791
TI  - Role of the actin cytoskeleton in T cell absorption and internalization of
      ligands from APC.
AB  - A feature of T-APC interaction is that, via either TCR or CD28, T cells can
      absorb molecules from APC on to the cell surface and then internalize these
      molecules. Here, using both normal and TCR-transgenic T cells, we investigated
      the mechanism of T cell absorption of molecules from APC and the role of the
      cytoskeleton. The results show that although activated T cells could absorb APC
      molecules in the form of cell fragments, uptake of molecules by resting T cells
      required direct T-APC interaction. Based on studies with latrunculin B, surface
      absorption of molecules by resting T cells was crucially dependent upon the actin
      cytoskeleton for both CD28- and TCR-mediated absorption. Significantly, however,
      TCR-mediated absorption became strongly resistant to latrunculin B when the
      concentration of MHC-bound peptide on APC was raised to a high level, implying
      that the actin cytoskeleton is only important for absorption when the density of
      receptor/ligand interaction is low. By contrast, in all situations tested, the
      actin cytoskeleton played a decisive role in controlling T cell internalization
      of ligands from the cell surface.

PMID- 11290792
TI  - LOX-1 supports adhesion of Gram-positive and Gram-negative bacteria.
AB  - Adhesion of bacteria to vascular endothelial cells as well as mucosal cells and
      epithelial cells appears to be one of the initial steps in the process of
      bacterial infection, including infective endocarditis. We examined whether lectin
      like oxidized low-density lipoprotein receptor 1 (LOX-1), a member of scavenger
      receptor family molecules with C-type lectin-like structure, can support adhesion
      of Gram-positive and Gram-negative bacteria. Chinese hamster ovary-K1 (CHO-K1)
      cells stably expressing LOX-1 can support binding of FITC-labeled Staphylococcus
      aureus and Escherichia coli, which was suppressed by poly(I) and an anti-LOX-1
      mAb. Adhesion of these bacteria to LOX-1 does not require divalent cations or
      serum factors and can be supported under both static and nonstatic conditions.
      Cultured bovine aortic endothelial cells (BAEC) can also support adhesion of FITC
      labeled S. aureus, which was similarly suppressed by poly(I) and an anti-LOX-1
      mAb. In contrast, binding of FITC-labeled E. coli to BAEC was partially inhibited
      by the anti-LOX-1 mAb, and poly(I) did not block FITC-labeled E. coli adhesion to
      BAEC, but, rather, enhanced it under a static condition. TNF-alpha increased LOX
      1-dependent adhesion of E. coli, but not that of S. aureus, suggesting that S.
      aureus adhesion to BAEC may require additional molecules, which cooperate with
      LOX-1 and suppressed by TNF-alpha. Taken together, LOX-1 can work as a cell
      surface receptor for Gram-positive and Gram-negative bacteria, such as S. aureus
      and E. coli, in a mechanism similar to that of class A scavenger receptors;
      however, other unknown molecules may also be involved in the adhesion of E. coli
      to BAEC, which is enhanced by poly(I).

PMID- 11290793
TI  - CD40 signaling converts a minimally immunogenic antigen into a potent vaccine
      against the intracellular pathogen Listeria monocytogenes.
AB  - Conventional vaccination strategies have failed for numerous pathogens, and the
      development of novel approaches to vaccine development is a major public health
      priority. Killed or subunit vaccines represent an attractive approach due to
      their safety, but they suffer from low immunogenicity and generally require
      adjuvants. In this study, the possibility of harnessing CD40 signaling for
      enhancing the immunogenicity of killed vaccines was investigated. Intravenous
      immunization of C57BL/6 mice with heat-killed Listeria monocytogenes (HKL)
      induced minimal immunity, but HKL administered together with an agonistic anti
      CD40 mAb induced high levels of both CD4(+) and CD8(+) T cells capable of
      producing IFN-gamma following in vitro HKL stimulation. HKL/anti-CD40 vaccination
      elicited robust protection against subsequent Listeria challenge. Approximately
      1000-fold fewer bacteria were detected in the liver and spleen of vaccinated
      mice, and vaccinated mice were also able to resist a normally lethal Listeria
      challenge. CD40-mediated adjuvant activity required endogenous IL-12 at the time
      of vaccination, and protection was mediated by both CD8(+) and CD4(+) T cells.
      Thus, CD40 signaling can deliver potent adjuvant activity for vaccination against
      intracellular pathogens and is particularly effective for pathogens requiring
      both CD4(+) and CD8(+) T cells for effective control.

PMID- 11290794
TI  - The potency and durability of DNA- and protein-based vaccines against Leishmania
      major evaluated using low-dose, intradermal challenge.
AB  - DNA- and protein- based vaccines against cutaneous leishmaniasis due to
      Leishmania major were evaluated using a challenge model that more closely
      reproduces the pathology and immunity associated with sand fly-transmitted
      infection. C57BL/6 mice were vaccinated s.c. with a mixture of plasmid DNAs
      encoding the Leishmania Ags LACK, LmSTI1, and TSA (AgDNA), or with autoclaved L.
      major promastigotes (ALM) plus rIL-12, and the mice were challenged by
      inoculation of 100 metacyclic promastigotes in the ear dermis. When challenged at
      2 wk postvaccination, mice receiving AgDNA or ALM/rIL-12 were completely
      protected against the development of dermal lesions, and both groups had a 100
      fold reduction in peak dermal parasite loads compared with controls. When
      challenged at 12 wk, mice vaccinated with ALM/rIL-12 maintained partial
      protection against dermal lesions and their parasite loads were no longer
      significantly reduced, whereas the mice vaccinated with AgDNA remained completely
      protected and had a 1000-fold reduction in dermal parasite loads. Mice vaccinated
      with AgDNA also harbored few, if any, parasites in the skin during the chronic
      phase, and their ability to transmit L. major to vector sand flies was completely
      abrogated. The durable protection in mice vaccinated with AgDNA was associated
      with the recruitment of both CD8(+) and CD4(+) T cells to the site of intradermal
      challenge and with IFN-gamma production by CD8(+) T cells in lymph nodes draining
      the challenge site. These data suggest that under conditions of natural
      challenge, DNA vaccination has the capacity to confer complete protection against
      cutaneous leishmaniasis and to prevent the establishment of infection reservoirs.

PMID- 11290795
TI  - Fibronectin binding protein A of Staphylococcus aureus can mediate human T
      lymphocyte adhesion and coactivation.
AB  - The extracellular matrix protein fibronectin (FN) mediates the adhesion of
      bacteria as well as T lymphocytes. Mammalian cells express integrins
      alpha(4)beta(1) and alpha(5)beta(1) as the major FN-binding cell surface
      receptors. Bacteria such as Staphylococcus aureus, also express FN-binding
      receptors that are important for adherence to host tissue and initiation of
      infection. The S. aureus FN-binding protein, FnbpA, has been previously
      identified, and recombinant proteins that correspond to distinct functional
      regions of this protein have been made. Three recombinant truncated forms of
      FnbpA, rFnbpA(37-881), rFnbpA(37-605), and rFnbpA(620-881), were examined for
      effects on in vitro adhesion and coactivation of human T lymphocytes. These
      proteins, when coimmobilized with anti-CD3 mAb, activated T lymphocyte
      proliferation. The coactivation signal generated by the rFnbpA proteins required
      medium containing serum with FN. Furthermore, the costimulatory signal could be
      restored in FN-depleted serum when the rFnbpAs were preloaded with soluble FN.
      Monoclonal Ab blocking studies revealed that integrin alpha(5)beta(1) is the
      major receptor responsible for the rFnbpA costimulatory signal. Shear flow cell
      detachment assays confirmed that lymphocytes can bind to FN captured by the
      rFnbpA proteins. These results suggest that the S. aureus rFnbpA can interact
      with integrin alpha(5)beta(1) via an FN bridge to mediate adhesion and
      costimulatory signals to T lymphocytes.

PMID- 11290796
TI  - Platelet-activating factor-induced early activation of NF-kappa B plays a crucial
      role for organ clearance of Candida albicans.
AB  - In this study, we have investigated the mechanisms underlying organ
      susceptibility to candida infection. Infection of BALB/c mice with Candida
      albicans led to both an early (1-8 h) and late (24-48 h) activation of NF-kappaB
      in the organs resistant to C. albicans, including the lung and spleen. In
      susceptible organs such as the kidneys, early activation of NF-kappaB was not
      observed. The kinetics of TNF-alpha mRNA expression paralleled those of NF-kappaB
      activation in all organs examined. Blocking the effects of endogenous platelet
      activating factor (PAF) by pretreatment with the PAF antagonist BN50739 or
      antioxidants significantly reduced the early activity of NF-kappaB and TNF-alpha
      mRNA expression, and increased the recovery of C. albicans in the lung and
      spleen. Importantly, administration of PAF 5 min prior to the infection resulted
      in the appearance of early activities of NF-kappaB and TNF-alpha mRNA expression,
      followed by a nearly complete clearance of the organisms in the kidneys.
      Pretreatment with anti-TNF-alpha Ab resulted in an enhanced susceptibility to C.
      albicans, and the PAF-mediated resistance was abrogated by anti-TNF-alpha in all
      organs examined. These data indicated that endogenously produced PAF in response
      to C. albicans is a key molecule involved in the early activation of NF-kappaB,
      which, in turn, renders the organ resistant to the fungus by promoting the
      production of anti-candidal proinflammatory cytokines such as TNF-alpha.
      Susceptible organs, including the kidneys, lack the capacity to generate a
      sufficient PAF-induced early NF-kappaB response.

PMID- 11290797
TI  - Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC,
      and CX3C chemokines.
AB  - STRL33/BONZO/TYMSTR is an orphan chemokine and HIV/SIV coreceptor receptor that
      is expressed on activated T lymphocytes. We describe an expression cloning
      strategy whereby we isolated a novel chemokine, which we name CXCL16. CXCL16 is
      an alpha (CXC) chemokine but also has characteristics of CC chemokines and a
      structure similar to fractalkine (neurotactin) in having a transmembrane region
      and a chemokine domain suspended by a mucin-like stalk. A recombinant version of
      CXCL16 fails to mediate chemotaxis to all known chemokine receptor transfectants
      tested but does mediate robust chemotaxis, high affinity binding, and calcium
      mobilization to Bonzo receptor transfectants, indicating that this is a unique
      receptor ligand interaction. In vitro polarized T cell subsets including Th1,
      Th2, and Tr1 cells express functional Bonzo, suggesting expression of this
      receptor in chronic inflammation, which we further verified by demonstration of
      CXCL16-mediated migration of tonsil-derived CD4(+) T lymphocytes. CXCL16 is
      expressed on the surface of APCs including subsets of CD19(+) B cells and CD14(+)
      monocyte/macrophages, and functional CXCL16 is also shed from macrophages. The
      combination of unique structural features of both Bonzo and CXCL16 suggest that
      this interaction may represent a new class of ligands for this receptor family.
      Additionally, this chemokine might play a unique dual role of attracting
      activated lymphocyte subsets during inflammation as well as facilitating immune
      responses via cell-cell contact.

PMID- 11290798
TI  - N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes.
AB  - Glucosamine represents one of the most commonly used drugs to treat
      osteoarthritis. However, mechanisms of its antiarthritic activities are still
      poorly understood. The present study identifies a novel mechanism of glucosamine
      mediated anti-inflammatory activity. It is shown that both glucosamine and N
      acetylglucosamine inhibit IL-1beta- and TNF-alpha-induced NO production in normal
      human articular chondrocytes. The effect of the sugars on NO production is
      specific, since several other monosaccharides, including glucose, glucuronic
      acid, and N-acetylmannosamine, do not express this activity. Furthermore, N
      acetylglucosamine polymers, including the dimer and the trimer, also do not
      affect NO production. The observed suppression of IL-1beta-induced NO production
      is associated with inhibition of inducible NO synthase mRNA and protein
      expression. In addition, N-acetylglucosamine also suppresses the production of IL
      1beta-induced cyclooxygenase-2 and IL-6. The constitutively expressed
      cyclooxygenase-1, however, was not affected by the sugar. N-acetylglucosamine
      mediated inhibition of the IL-1beta response of human chondrocytes was not
      associated with the decreased inhibition of the mitogen-activated protein kinases
      c-Jun N-terminal kinase, extracellular signal-related kinase, and p38, nor with
      activation of the transcription factor NF-kappaB. In conclusion, these results
      demonstrate that N-acetylglucosamine expresses a unique range of activities and
      identifies a novel mechanism for the inhibition of inflammatory processes.

PMID- 11290800
TI  - Resident and infiltrating central nervous system APCs regulate the emergence and
      resolution of experimental autoimmune encephalomyelitis.
AB  - During experimental autoimmune encephalomyelitis (EAE), autoreactive Th1 T cells
      invade the CNS. Before performing their effector functions in the target organ, T
      cells must recognize Ag presented by CNS APCs. Here, we investigate the nature
      and activity of the cells that present Ag within the CNS during myelin
      oligodendrocyte glycoprotein-induced EAE, with the goal of understanding their
      role in regulating inflammation. Both infiltrating macrophages (Mac
      1(+)CD45(high)) and resident microglia (Mac-1(+)CD45(int)) expressed MHC-II, B7
      1, and B7-2. Macrophages and microglia presented exogenous and endogenous CNS Ags
      to T cell lines and CNS T cells, resulting in IFN-gamma production. In contrast,
      Mac-1(-) cells were inefficient APCs during EAE. Late in disease, after mice had
      partially recovered from clinical signs of disease, there was a reduction in Ag
      presenting capability that correlated with decreased MHC-II and B7-1 expression.
      Interestingly, although CNS APCs induced T cell cytokine production, they did not
      induce proliferation of either T cell lines or CNS T cells. This was attributable
      to production by CNS cells (mainly by macrophages) of NO. T cell proliferation
      was restored with an NO inhibitor, or if the APCs were obtained from inducible NO
      synthase-deficient mice. Thus, CNS APCs, though essential for the initiation of
      disease, also play a down-regulatory role. The mechanisms by which CNS APCs limit
      the expansion of autoreactive T cells in the target organ include their
      production of NO, which inhibits T cell proliferation, and their decline in Ag
      presentation late in disease.

PMID- 11290799
TI  - Induction of cross-tolerance by lipopolysaccharide and highly purified
      lipoteichoic acid via different Toll-like receptors independent of paracrine
      mediators.
AB  - Exposure of macrophages to LPS induces a state of hyporesponsiveness to
      subsequent stimulation with LPS termed LPS desensitization or tolerance. To date,
      it is not known whether similar mechanisms of macrophage refractoriness are
      induced on contact with components of Gram-positive bacteria. In the present
      study, we demonstrate that pretreatment with highly purified lipoteichoic acid
      (LTA) results in suppression of cytokine release on restimulation with LTA in
      vitro and in vivo in both C3H/HeN and C3H/HeJ mice, but not in macrophages from
      Toll-like receptor (TLR)-2-deficient mice. Furthermore, desensitization in
      response to LPS or LTA exposure also inhibits responses to the other stimulus
      ("cross-tolerance"), suggesting that signaling pathways shared by TLR2 and TLR4
      are impaired during tolerance. Finally, we show that LPS- or LTA-induced cross
      tolerance is not transferred to hyporesponsive cells cocultured with LPS/LTA
      responsive macrophages, showing that soluble mediators do not suffice for
      tolerance induction in neighboring cells.

PMID- 11290801
TI  - Production of chemokines in vivo in response to microbial stimulation.
AB  - Members of the chemokine gene superfamily are known to play a central role in
      leukocyte extravasation; however, their involvement in acute inflammation in
      response to micro-organisms has not yet been well studied. We have therefore
      investigated the role of murine macrophage-inflammatory protein (muMIP) 1alpha
      and muMIP-2 in the inflammatory response mounted against the bacteria Salmonella
      enteritidis and the Sacchromyces cerevisiae cell wall component, zymosan.
      Leukocyte extravasation was monitored in murine s.c. air pouches. Both agonists
      induced accumulation of leukocytes in a dose- and time-dependent manner, with the
      response peaking after 4 h and declining thereafter. The inflammatory exudate
      comprised mainly neutrophils; however, an increase in eosinophil accumulation was
      also observed in response to zymosan. The production of both muMIP-1alpha and
      muMIP-2 increased with time in response to both the agonists, although production
      was more sustained in response to the bacteria. Prior treatment of mice with
      neutralizing Abs against muMIP-1alpha or muMIP-2, either alone or in combination,
      failed to attenuate the accumulation of leukocytes in response to the agonists.
      In contrast, the anti-muMIP-2 Abs significantly inhibited leukocyte recruitment
      in response to S. enteritidis in complement-deficient mice. Taken together, these
      data show that while muMIP-1alpha and muMIP-2 are produced in response to
      phagocytosis of micro-organisms in s.c. tissue, under these circumstances
      components of the complement pathway appear to play a dominant role in the
      recruitment of neutrophils.

PMID- 11290802
TI  - Enhanced airway Th2 response after allergen challenge in mice deficient in CC
      chemokine receptor-2 (CCR2).
AB  - To evaluate the role of CCR2 in allergic asthma, mutant mice deficient in CCR2
      (CCR2(-/-)) and intact mice were sensitized with i.p. OVA with alum on days 0 and
      7, and challenged by inhalation with nebulization of either OVA or saline. Airway
      hyperreactivity, measured by the methacholine-provoked increase in enhanced
      pause, was significantly increased (p < 0.05) in OVA-challenged CCR2(-/-) mutant
      mice, compared with comparably challenged CCR2(+/+) mice. OVA-challenged CCR2(-/
      ) mutants also were also found to have enhanced bronchoalveolar lavage fluid
      eosinophilia, peribronchiolar cellular cuffing, and Ig subclass switching, with
      increase in OVA-specific IgG(1) and IgE. In addition, RNase protection assay
      revealed increased whole lung expression of IL-13 in OVA-challenged CCR2(-/-)
      mutants. Unexpectedly, serum monocyte chemotactic protein-1 levels were 8-fold
      higher in CCR2(-/-) mutants than in CCR2(+/+) mice sensitized to OVA, but OVA
      challenge had no additional effect on circulating monocyte chemotactic protein-1
      in either genotype. Ag stimulation of lymphocytes isolated from OVA-sensitized
      CCR2 mutants revealed a significant increase (p < 0.05) in IL-5 production, which
      differed from OVA-stimulated lymphocytes from sensitized CCR2(+/+) mice. These
      experiments demonstrate an enhanced response in airway reactivity and in lung
      inflammation in CCR2(-/-) mutant mice compared with comparably sensitized and
      challenged CCR2(+/+) mice. These observations suggest that CC chemokines and
      their receptors are involved in immunomodulation of atopic asthma.

PMID- 11290803
TI  - Fc gamma RIII-mediated production of TNF-alpha induces immune complex alveolitis
      independently of CXC chemokine generation.
AB  - We recently demonstrated a codominant role of C5aR and FcgammaRIII in the
      initiation of IgG immune complex-mediated inflammation in mice. In this study, we
      investigated the relative contribution of FcgammaRIII in the generation of
      several cytokines during experimental hypersensitivity pneumonitis/alveolitis in
      vivo. Induction of immune complex-alveolitis in C57BL/6 mice resulted in strong
      accumulation of neutrophils into the lung and enhanced chemotactic activity
      within bronchoalveolar lavage fluid accompanied by an increased production of the
      proinflammatory cytokines TNF-alpha and IL-1beta as well as the ELR-CXC
      chemokines macrophage inflammatory protein-2 (MIP-2) and cytokine-induced
      neutrophil chemoattractant (KC). FcgammaRIII-deficient C57BL/6 mice (FcgammaRIII(
      /-)) showed a marked reduction of the inflammatory response due to decreased
      production of TNF-alpha, IL-1beta, and MIP-2. Results obtained in C57BL/6 mice
      either lacking the TNF-alpha class I receptor (TNF-alphaRI(-/-)) or treated with
      neutralizing anti-TNF-alpha mAb demonstrated an essential contribution of TNF
      alpha for mediating IL-1beta release, neutrophil influx, and hemorrhage.
      Surprisingly, MIP-2 and KC chemokine levels remained largely unaffected in TNF
      alphaRI(-/-) mice or after functional inhibition of TNF-alpha. These data suggest
      that in immune complex alveolitis, the activation of FcgammaRIII may induce
      divergent downstream effector pathways with TNF-alpha acting independently of CXC
      chemokines to trigger the inflammatory response in C57BL/6 mice.

PMID- 11290804
TI  - Intracellular pool of IL-10 receptors in specific granules of human neutrophils:
      differential mobilization by proinflammatory mediators.
AB  - IL-10 has a wide range of effects tending to control inflammatory responses. We
      used flow cytometry to study IL-10 binding at the polymorphonuclear neutrophil
      (PMN) surface and its modulation by various proinflammatory agents. Little IL-10
      bound to the surface of resting PMN. However, binding was strongly increased
      after stimulation with LPS and proinflammatory cytokines such as TNF and GM-CSF.
      IL-1 and IL-8 did not significantly modify IL-10 binding. Cycloheximide had no
      effect on TNF-induced IL-10 binding, strongly suggesting the release of a pre
      existing pool of IL-10R rather than de novo receptor synthesis by PMN. This was
      confirmed by the inhibitory effect of pentoxifylline, an inhibitor of
      degranulation. The existence of an intracellular pool of IL-10R was shown by flow
      cytometry, immunocytochemical staining, and Western blotting with several anti
      human IL-10R Abs. In subcellular fractions of resting PMN, IL-10R was mainly
      located in the specific granule fraction, and was absent from azurophil granules
      and cytosol. We also tested the mobilization of specific granules by measuring
      the release of lactoferrin, their reference marker. The differential effects of
      the proinflammatory agents on IL-10 binding matched their effects on lactoferrin
      release and may therefore be related to differential mobilization of specific
      granules by these agents. Furthermore, the kinetics of TNF-induced up-regulation
      of IL-10 binding to PMN ran parallel to the kinetics of the inhibitory effect of
      IL-10 on the oxidative burst, suggesting a key role of IL-10R mobilization from
      specific granules to the membranes in optimal regulation of inflammatory
      responses.

PMID- 11290806
TI  - Therapeutic effect of IL-13 immunoneutralization during chronic experimental
      fungal asthma.
AB  - IL-13 and IL-4 are key contributors to the asthmatic phenotype. The temporal role
      of these cytokines in airway function, inflammation, and remodeling were assessed
      in a chronic murine model of Asperigillus fumigatus-induced allergic asthma. IL
      13 and IL-4 protein levels were significantly elevated by 30 days after conidia
      challenge in A. fumigatus-sensitized mice. Furthermore, IL-13Ralpha1 mRNA
      expression was significantly elevated 7 days after conidia challenge and remained
      elevated until day 21. In contrast, IL-13Ralpha2 mRNA expression, although
      constitutively expressed in naive lung, was absent in the lungs of A. fumigatus
      sensitized mice both before and after conidia challenge. Membrane-bound IL-4R
      mRNA expression was significantly elevated 7 days after conidia challenge;
      however, soluble IL-4R mRNA expression was increased 30 days after conidia
      challenge. Immunoneutralization of IL-13 between days 14 and 30 or days 30 and 38
      after fungal sensitization and challenge significantly attenuated airway
      hyperresponsiveness, collagen deposition, and goblet cell hyperplasia at day 38
      after conidia challenge; however, the effects of IL-4 immunoneutralization during
      the same time periods were not as marked. IFN-gamma and IL-12 release after
      Aspergillus Ag restimulation was elevated from spleen cells isolated from mice
      treated with IL-4 anti-serum compared with IL-13 anti-serum or normal rabbit
      serum-treated mice. This study demonstrates a pronounced therapeutic effect of IL
      13-immunoneutralization at extended time points following the induction of
      chronic asthma. Most importantly, these therapeutic effects were not reversed
      following cessation of treatment, and IL-13 anti-serum treatment did not alter
      the systemic immune response to Ag restimulation, unlike IL-4
      immunoneutralization. Therefore, IL-13 provides an attractive therapeutic target
      in allergic asthma.

PMID- 11290805
TI  - Regulatory effects of eotaxin on acute lung inflammatory injury.
AB  - Eotaxin, which is a major mediator for eosinophil recruitment into lung, has
      regulatory effects on neutrophil-dependent acute inflammatory injury triggered by
      intrapulmonary deposition of IgG immune complexes in rats. In this model, eotaxin
      mRNA and protein were up-regulated during the inflammatory response, resulting in
      eotaxin protein expression in alveolar macrophages and in alveolar epithelial
      cells. Ab-induced blockade of eotaxin in vivo caused enhanced NF-kappaB
      activation in lung, substantial increases in bronchoalveolar lavage levels of
      macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil
      chemoattractant (CINC), and increased MIP-2 and CINC mRNA expression in alveolar
      macrophages. In contrast, TNF-alpha levels were unaffected, and IL-10 levels
      fell. Under these experimental conditions, lung neutrophil accumulation was
      significantly increased, and vascular injury, as reflected by extravascular leak
      of (125)I-albumin, was enhanced. Conversely, when recombinant eotaxin was
      administered in the same inflammatory model of lung injury, bronchoalveolar
      lavage levels of MIP-2 were reduced, as was neutrophil accumulation and the
      intensity of lung injury. In vitro stimulation of rat alveolar macrophages with
      IgG immune complexes greatly increased expression of mRNA and protein for MIP-2,
      CINC, MIP-1alpha, MIP-1beta, TNF-alpha, and IL-1beta. In the copresence of
      eotaxin, the increased levels of MIP-2 and CINC mRNAs were markedly diminished,
      whereas MIP-1alpha, MIP-1beta, TNF-alpha, and IL-1beta expression of mRNA and
      protein was not affected. These data suggest that endogenous eotaxin, which is
      expressed during the acute lung inflammatory response, plays a regulatory role in
      neutrophil recruitment into lung and the ensuing inflammatory damage.

PMID- 11290807
TI  - Lethal hepatitis after gene transfer of IL-4 in the liver is independent of
      immune responses and dependent on apoptosis of hepatocytes: a rodent model of IL
      4-induced hepatitis.
AB  - The putative role of IL-4 in human and animal models of hepatitis has not yet
      been directly determined. We now report that direct expression of IL-4 in the
      liver of rats or mice using recombinant adenoviruses coding for rat or mouse IL-4
      (AdrIL-4 and AdmIL-4, respectively) results in a lethal, dose-dependent
      hepatitis. The hepatitis induced by IL-4 was characterized by hepatocyte
      apoptosis and a massive monocyte/macrophage infiltrate. IL-4-induced hepatitis
      was independent of T cell-mediated immune responses. Hepatitis occurred even
      after gene transfer of IL-4 into nude rats, CD8-depleted rats, cyclosporine A
      treated rats, or recombinase-activating gene 2(-/-) immunodeficient mice.
      Peripheral depletion of leukocytes using high doses of cyclophosphamide, and/or
      the specific depletion of liver macrophages with liposome-encapsulated
      dichloromethylene diphosphonate in rats did not block lethal IL-4-induced
      hepatitis. Direct transduction of hepatocytes with adenoviruses was not
      essential, since injection of AdrIL-4 into the hind limb induced an identical
      hepatitis. Finally, primary rat hepatocytes in culture also showed apoptosis when
      cultured in the presence of rIL-4. IL-4-dependent hepatitis was associated with
      increases in the intrahepatic levels of IFN-gamma, TNF-alpha, and Fas ligand.
      Administration of AdmIL-4 to IFN-gamma, TNF-alpha receptor type I, or TNF-alpha
      receptor type II knockout mice also resulted in lethal hepatitis, whereas a
      moderate protection was observed in Fas-deficient lpr mice. IL-4-dependent
      hepatocyte apoptosis could be abolished by treatment with caspase inhibitory
      peptides. Our results thus demonstrate that IL-4 causes hepatocyte apoptosis,
      which is only partially dependent on the activation of Apo-1-Fas signaling and is
      largely independent of any immune cells in the liver.

PMID- 11290808
TI  - Highly efficient transduction of human monocyte-derived dendritic cells with
      subgroup B fiber-modified adenovirus vectors enhances transgene-encoded antigen
      presentation to cytotoxic T cells.
AB  - The efficiency of dendritic cells (DC) as immunotherapeutic vaccines critically
      depends on optimal delivery of target Ags. Although DC modified by subgroup C
      type 5 recombinant adenoviruses (rAd5) provide encouraging results, their
      clinical application is hampered by the need for high viral titers to achieve
      sufficient gene transfer, due to the lack of the Ad5 fiber receptor. We now
      demonstrate that rAd5 carrying subgroup B Ad fibers are up to 100-fold more
      potent than classical rAd5 for gene transfer and expression in human DC, rAd5
      with a type 35 fiber (rAd5F35) being the most efficient vector. This improvement
      relates to a greater and faster virus entry and to an increased transgene
      expression especially following DC maturation. Furthermore, these new vectors
      possess enhanced synergistic effects with other activation signals to trigger DC
      maturation. Consequently, rAd5F35-infected DC engineered to express the gp100
      melanoma-associated Ag largely exceed rAd5-infected DC in activating gp100
      specific CTL. Finally, the DC infection pattern of rAd5F35 is fully conserved
      when DC are in the vicinity of primary skin-derived fibroblasts, suggesting this
      vector as a candidate for in vivo targeting of DC. Thus, subgroup B fiber
      modified rAd5 constitute a major breakthrough in the exploitation of ex vivo rAd
      targeted DC as clinically relevant vaccines and may also be suitable for in vivo
      genetic modification of DC.

PMID- 11290809
TI  - Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich
      syndrome.
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency
      disease, arising from mutations of the WAS-protein (WASP) gene. Previously, we
      have reported that mononuclear cells from WAS patients showed lack/reduced of the
      intracellular WASP (WASP(dim)) by flow cytometric analysis, and analysis of WASP
      by flow cytometry (FCM-WASP) was useful for WAS diagnosis. In this study, we
      report a WAS patient who showed the unique pattern of FCM-WASP. The patient had
      the small population of normal expression of WASP (WASP(bright)) mononuclear
      cells together with the major WASP(dim) population. The WASP(bright) cells were
      detected in T cells, not in B cells or in monocytes. Surprisingly, the molecular
      studies of the WASP(bright) cells revealed that the inherited mutation of WASP
      gene was reversed to normal. His mother was proved as a WAS carrier, and HLA
      studies and microsatellite polymorphic studies proved that the WASP(bright) cells
      were derived from the patient himself. Therefore, we concluded that the
      WASP(bright) cells were resulted from spontaneous in vivo reversion of the
      inherited mutation. Furthermore, the scanning electron microscopic studies
      indicated that WASP-positive cells from the patient restored the dense
      microvillus surface projections that were hardly observed in the WASP(dim) cells.
      This case might have significant implications regarding the prospects of the
      future gene therapy for WAS patients.

PMID- 11290810
TI  - Targeting antigen in mature dendritic cells for simultaneous stimulation of CD4+
      and CD8+ T cells.
AB  - Due to their potent immunostimulatory capacity, dendritic cells (DC) have become
      the centerpiece of many vaccine regimens. Immature DC (DCimm) capture, process,
      and present Ags to CD4(+) lymphocytes, which reciprocally activate DCimm through
      CD40, and the resulting mature DC (DCmat) loose phagocytic capacity, but acquire
      the ability to efficiently stimulate CD8(+) lymphocytes. Recombinant vaccinia
      viruses (rVV) provide a rapid, easy, and efficient method to introduce Ags into
      DC, but we observed that rVV infection of DCimm results in blockade of DC
      maturation in response to all activation signals, including CD40L, monocyte
      conditioned medium, LPS, TNF-alpha, and poly(I:C), and failure to induce a CD8(+)
      response. By contrast, DCmat can be infected with rVV and induce a CD8(+)
      response, but, having lost phagocytic activity, fail to process the Ag via the
      exogenous class II pathway. To overcome these limitations, we used the CMV
      protein pp65 as a model Ag and designed a gene containing the lysosomal
      associated membrane protein 1 targeting sequence (Sig-pp65-LAMP1) to target pp65
      to the class II compartment. DCmat infected with rVV-Sig-pp65-LAMP1 induced
      proliferation of pp65-specific CD4(+) clones and efficiently induced a pp65
      specific CD4(+) response, suggesting that after DC maturation the intracellular
      processing machinery for class II remains intact for at least 16 h. Moreover,
      infection of DCmat with rVV-Sig-pp65-LAMP1 resulted in at least equivalent
      presentation to CD8(+) cells as infection with rVV-pp65. These results
      demonstrate that despite rVV interference with DCimm maturation, a single
      targeting vector can deliver Ags to DCmat for the effective simultaneous
      stimulation of both CD4(+) and CD8(+) cells.

PMID- 11290811
TI  - Posttransplant administration of donor leukocytes induces long-term acceptance of
      kidney or liver transplants by an activation-associated immune mechanism.
AB  - Donor leukocytes play a dual role in rejection and acceptance of transplanted
      organs. They provide the major stimulus for rejection, and their removal from the
      transplanted organ prolongs its survival. Paradoxically, administration of donor
      leukocytes also prolongs allograft survival provided that they are administered 1
      wk or more before transplantation. Here we show that administration of donor
      leukocytes immediately after transplantation induced long-term acceptance of
      completely MHC-mismatched rat kidney or liver transplants. The majority of long
      term recipients of kidney transplants were tolerant of donor-strain skin grafts.
      Acceptance was associated with early activation of recipient T cells in the
      spleen, demonstrated by a rapid increase in IL-2 and IFN-gamma at that site
      followed by an early diffuse infiltrate of activated T cells and apoptosis within
      the tolerant grafts. In contrast, IL-2 and IFN-gamma mRNA were not increased in
      the spleens of rejecting animals, and the diffuse infiltrate of activated T cells
      appeared later but resulted in rapid graft destruction. These results define a
      mechanism of allograft acceptance induced by donor leukocytes that is associated
      with activation-induced cell death of recipient T cells. They demonstrate for the
      first time that posttransplant administration of donor leukocytes leads to organ
      allograft tolerance across a complete MHC class I plus class II barrier, a
      finding with direct clinical application.

PMID- 11290812
TI  - Intermolecular antigen spreading occurs during the preclinical period of human
      type 1 diabetes.
AB  - Intra- and intermolecular spreading of T cell responses to autoantigens has been
      implicated in the pathogenesis of autoimmune diseases. Therefore, we questioned
      whether T cell responses from subjects identified as at-risk (positive for
      autoantibody reactivity to islet proteins) for the development of type 1
      diabetes, a cell-mediated autoimmune disease, would demonstrate intermolecular Ag
      spreading of T cell responses to islet cell proteins. Previously, we have
      demonstrated that by the time subjects develop type 1 diabetes, they have T cell
      responses to numerous islet proteins, whereas T cells from normal controls
      respond to a limited number of islet proteins. Initial testing of PBMC responses
      from 25 nondiabetic at-risk subjects demonstrated that 16 of the 25 subjects have
      PBMC responses to islet proteins similar to controls. Fourteen of these 16
      subjects were available for follow-up. Eleven of the 14 developed T cell
      responses to increasing numbers of islet proteins, and 6 of these subjects
      developed type 1 diabetes. In the nine subjects who already demonstrated T cell
      Ag spreading at the initial visit, four were available for follow-up. Of these
      four, two had increases in T cell reactivity to islet proteins, while two
      maintained their initial levels of T cell reactivity. We also observed Ag
      spreading in autoantibody reactivity to islet proteins in nine of the 18 at-risk
      subjects available for follow-up. Our data strongly support the conclusion that
      intermolecular spreading of T cell and Ab responses to islet proteins occurs
      during the preclinical period of type 1 diabetes.

PMID- 11290813
TI  - Identification of epitope regions recognized by tumor inhibitory and stimulatory
      anti-ErbB-2 monoclonal antibodies: implications for vaccine design.
AB  - The self-oncoprotein ErbB-2 is overexpressed in a number of malignancies. The
      presence of endogenous anti-ErbB-2 Ab and T cell immune responses to this protein
      in cancer patients has made ErbB-2 an attractive target for active immunization.
      However, the finding that murine anti-ErbB-2 Abs can have stimulatory,
      inhibitory, or no effects on cancer cell growth suggests that an inappropriately
      induced immune response may have an adverse effect. To ensure the induction of a
      beneficial Ab response, it is important to identify the epitopes recognized by
      these Abs. In this study we have used phage-displayed ErbB-2 gene fragment
      libraries and synthetic peptides to epitope-map a panel of anti-ErbB-2 mAbs. The
      epitopes of three mAbs, N12, N28, and L87, were successfully located to C531
      A586, T216-C235, and C220-C235 of ErbB-2, respectively. It was found that while
      N12 inhibited tumor cell proliferation, N28 stimulated the proliferation of a
      subset of breast cancer cell lines overexpressing ErbB-2. The peptide region
      recognized by N12, (C531-A586; EP531), was used as an immunogen to selectively
      induce an inhibitory immune response in mice. Mice immunized with the GST fusion
      peptide (GST-EP531) recognized the peptide region EP531 as well as native ErbB-2.
      More importantly, Igs purified from mouse sera were able to inhibit up to 85% of
      tumor cell proliferation. In conclusion, our study provides direct evidence of
      the function-epitope relationship of anti-ErbB-2 Abs and also emphasizes the
      value of inducing a potent tumor inhibitory polyclonal Ab response by rationally
      selecting regions of ErbB-2 used for immunization.

PMID- 11290814
TI  - Anergy induction by dimeric TCR ligands.
AB  - T cells that recognize particular self Ags are thought to be important in the
      pathogenesis of autoimmune diseases. In multiple sclerosis, susceptibility is
      associated with HLA-DR2, which can present myelin-derived peptides to CD4(+) T
      cells. To generate molecules that target such T cells based on the specificity of
      their TCR, we expressed a soluble dimeric DR2-IgG fusion protein with a bound
      peptide from myelin basic protein (MBP). Soluble, dimeric DR2/MBP peptide
      complexes activated MBP-specific T cells in the absence of signals from
      costimulatory or adhesion molecules. This initial signaling through the TCR
      rendered the T cells unresponsive (anergic) to subsequent activation by peptide
      pulsed APCs. Fluorescent labeling demonstrated that anergic T cells were
      initially viable, but became susceptible to late apoptosis due to insufficient
      production of cytokines. Dimerization of the TCR with bivalent MHC class
      II/peptide complexes therefore allows the induction of anergy in human CD4(+) T
      cells with a defined MHC/peptide specificity.

PMID- 11290815
TI  - Molecular mimicry in Lyme arthritis demonstrated at the single cell level: LFA-1
      alpha L is a partial agonist for outer surface protein A-reactive T cells.
AB  - Antibiotic treatment-resistant Lyme arthritis is a chronic inflammatory joint
      disease that follows infection with Borrelia burgdorferi (BB:). A marked Ab and T
      cell response to BB: outer surface protein A (OspA) often develops during
      prolonged episodes of arthritis. Furthermore, cross-reaction between the
      bacterial OspA and human LFA-1alpha(L) at the T cell level and the inability to
      detect BB: in the joint implicate an autoimmune mechanism. To analyze the nature
      of response to OspA and LFA-1alpha(L), we used OspA-specific T cell hybrids from
      DR4 transgenic mice, as well as cloned human cells specific for OspA(165-184),
      the immunodominant epitope, from five DRB1*0401(+) patients, using OspA-MHC class
      II tetramers. Although OspA(165-184) stimulated nearly all OspA-specific human T
      cell clones tested to proliferate and secrete IFN-gamma and IL-13, LFA
      1alpha(L326-345) stimulated approximately 10% of these clones to proliferate and
      a greater percentage to secrete IL-13. Assays with LFA- or OspA-DR4 monomers
      revealed that higher concentrations of LFA-DR4 were needed to stimulate dual
      reactive T cell hybrids. Our analysis at the clonal level demonstrates that human
      LFA-1alpha(L326-345) behaves as a partial agonist, perhaps playing a role in
      perpetuating symptoms of arthritis.

PMID- 11290816
TI  - Anti-Sm B cell differentiation in Ig transgenic MRL/Mp-lpr/lpr mice: altered
      differentiation and an accelerated response.
AB  - To determine the regulation of B cells specific for the ribonucleoprotein Sm, a
      target of the immune system in human and mouse lupus, we have generated mice
      carrying an anti-Sm H chain transgene (2-12H). Anti-Sm B cells in nonautoimmune 2
      12H-transgenic (Tg) mice are functional, but, in the absence of immunization,
      circulating anti-Sm Ab levels are not different from those of non-Tg mice. In
      this report, we compare the regulation of anti-Sm B cells in nonautoimmune and
      autoimmune MRL/Mp-lpr/lpr (MRL/lpr) and bcl-2-22-Tg mice. Activation markers are
      elevated on splenic and peritoneal anti-Sm B cells of both nonautoimmune and
      autoimmune genetic backgrounds indicating Ag encounter. Although tolerance to Sm
      is maintained in 2-12H/bcl-2-22-Tg mice, it is lost in 2-12H-Tg MRL/lpr mice, as
      the transgene accelerates and increases the prevalence of the anti-Sm response.
      The 2-12H-Tg MRL/lpr mice have transitional anti-Sm B cells in the spleen similar
      to nonautoimmune mice. However, in contrast to nonautoimmune mice, there are few
      if any peritoneal anti-Sm B-1 cells. These data suggest that a defect in B-1
      differentiation may be a factor in the loss of tolerance to Sm and provide
      insight into the low prevalence of the anti-Sm response in lupus.

PMID- 11290817
TI  - T cell responses to HLA-A*0201-restricted peptides derived from human alpha
      fetoprotein.
AB  - alpha fetoprotein (AFP)-derived peptide epitopes can be recognized by human T
      cells in the context of MHC class I. We determined the identity of AFP-derived
      peptides, presented in the context of HLA-A*0201, that could be recognized by the
      human (h) T cell repertoire. We screened 74 peptides and identified 3 new AFP
      epitopes, hAFP(137-145), hAFP(158-166), and hAFP(325-334), in addition to the
      previously reported hAFP(542-550.) Each possesses two anchor residues and
      stabilized HLA-A*0201 on T2 cells in a concentration-dependent class I binding
      assay. The peptides were stable for 2-4 h in an off-kinetics assay. Each peptide
      induced peptide-specific T cells in vitro from several normal HLA-A*0201 donors.
      Importantly, these hAFP peptide-specific T cells also were capable of recognizing
      HLA-A*0201(+)/AFP(+) tumor cells in both cytotoxicity assays and IFN-gamma enzyme
      linked immunospot assays. The immunogenicity of each peptide was tested in vivo
      with HLA-A*0201/K(b)-transgenic mice. After immunization with each peptide
      emulsified in CFA, draining lymph node cells produced IFN-gamma on recognition of
      cells stably transfected with hAFP. Furthermore, AFP peptide-specific T cells
      could be identified in the spleens of mice immunized with dendritic cells
      transduced with an AFP-expressing adenovirus (AdVhAFP). Three of four AFP
      peptides could be identified by mass spectrometric analysis of surface peptides
      from an HLA-A*0201 human hepatocellular carcinoma (HCC) cell line. Thus,
      compelling immunological and physiochemical evidence is presented that at least
      four hAFP-derived epitopes are naturally processed and presented in the context
      of class I, are immunogenic, and represent potential targets for hepatocellular
      carcinoma immunotherapy.

PMID- 11290818
TI  - Effect of mutations of N- and C-terminal charged residues on the activity of
      LCAT.
AB  - On the basis of structural homology calculations, we previously showed that
      lecithin:cholesterol acyltransferase (LCAT), like lipases, belongs to the
      alpha/beta hydrolase fold family. As there is higher sequence conservation in the
      N-terminal region of LCAT, we investigated the contribution of the N- and C
      terminal conserved basic residues to the catalytic activity of this enzyme. Most
      basic, and some acidic residues, conserved among LCAT proteins from different
      species, were mutated in the N-terminal (residues 1;-210) and C-terminal
      (residues 211;-416) regions of LCAT. Measurements of LCAT-specific activity on a
      monomeric substrate, on low density lipoprotein (LDL), and on reconstituted high
      density lipoprotein (rHDL) showed that mutations of N-terminal conserved basic
      residues affect LCAT activity more than those in the C-terminal region. This
      agrees with the highest conservation of the alpha/beta hydrolase fold and
      structural homology with pancreatic lipase observed for the N-terminal region,
      and with the location of most of the natural mutants reported for human LCAT. The
      structural homology between LCAT and pancreatic lipase further suggests that
      residues R80, R147, and D145 of LCAT might correspond to residues R37, K107, and
      D105 of pancreatic lipase, which form the salt bridges D105-K107 and D105-R37.
      Natural and engineered mutations at residues R80, D145, and R147 of LCAT are
      accompanied by a substantial decrease or loss of activity, suggesting that salt
      bridges between these residues might contribute to the structural stability of
      the enzyme.

PMID- 11290819
TI  - ACAT inhibitor F-1394 prevents intimal hyperplasia induced by balloon injury in
      rabbits.
AB  - Acyl-CoA:cholesterol acyltransferase (ACAT) is thought to contribute
      significantly to lipid deposition in macrophages, which subsequently leads to the
      initiation and progression of atherosclerosis. The aim of the present study was
      to examine the influence of hypercholesterolemia on arterial hyperplasia induced
      by endothelial denudation and the direct effect of ACAT inhibition on lesion
      formation. Rabbits were fed either a cholesterol diet or a regular diet for 4
      weeks, and then the left common carotid arteries were denuded of endothelium.
      After the operation, all rabbits were kept on the regular diet for 2;-6 weeks.
      Two weeks after the denudation, the degree of intimal thickening and the number
      of proliferating cells (which were immunohistologically identified to be smooth
      muscle cells) were similar in hypercholesterolemic and normolipidemic rabbits.
      After that, both parameters progressively increased in hypercholesterolemic
      rabbits but declined in normolipidemic rabbits. Macrophages were apparent in the
      lesions only in hypercholesterolemic rabbits. Next, the effect of the ACAT
      inhibitor, (1S,2S)-2-[3-(2,2-dimethylpropyl)-3-nonylureido] cyclohexane-1-yl 3
      [(4R)-N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino]propionate (F-1394), on
      neointimal formation in hypercholesterolemic rabbits was examined. Oral
      administration of F-1394 significantly reduced neointimal thickening and the
      extent of macrophages in lesions without affecting serum cholesterol levels.
      These results suggest that hypercholesterolemia causes macrophage-derived foam
      cell accumulation in lesions, and that the progression of lesions is accelerated
      by the presence of macrophages. Moreover, the study shows that F-1394 prevents
      neointimal formation even in the presence of hypercholesterolemia, indicating
      that F-1394 may be useful for treating restenosis after percutaneous translumenal
      coronary angioplasty in hyperlipidemic patients.

PMID- 11290820
TI  - Lysosomal acid lipase-deficient mice: depletion of white and brown fat, severe
      hepatosplenomegaly, and shortened life span.
AB  - Lysosomal acid lipase (LAL) is essential for the hydrolysis of triglycerides (TG)
      and cholesteryl esters (CE) in lysosomes. A mouse model created by gene targeting
      produces no LAL mRNA, protein, or enzyme activity. The lal-/- mice appear normal
      at birth, survive into adulthood, and are fertile. Massive storage of TG and CE
      is observed in adult liver, adrenal glands, and small intestine. The age
      dependent tissue and gross progression in this mouse model are detailed here.
      Although lal-/- mice can be bred to give homozygous litters, they die at ages of
      7 to 8 months. The lal-/- mice develop enlargement of a single mesenteric lymph
      node that is full of stored lipids. At 6;-8 months of age, the lal-/- mice have
      completely absent inguinal, interscapular, and retroperitoneal white adipose
      tissue. In addition, brown adipose tissue is progressively lost. The plasma free
      fatty acid levels are significantly higher in lal-/- mice than age-matched lal+/+
      mice, and plasma insulin levels were more elevated upon glucose challenge. Energy
      intake was also higher in lal-/- male mice, although age-matched body weights
      were not significantly altered from age-matched lal+/+ mice. Early in the disease
      course, hepatocytes are the main storage cell in the liver; by 3;-8 months, the
      lipid-stored Kupffer cells progressively fill the liver. The involvement of
      macrophages throughout the body of lal-/- mice provide evidence for a critical
      nonappreciated role of LAL in cellular cholesterol and fatty acid metabolism,
      adipocyte differentiation, and fat mobilization.

PMID- 11290821
TI  - Identification of a fatty acid delta6-desaturase deficiency in human skin
      fibroblasts.
AB  - Polyunsaturated fatty acid (PUFA) utilization was investigated in skin
      fibroblasts cultured from a female patient with an inherited abnormality in lipid
      metabolism. These deficient human skin fibroblasts (DF) converted 85;-95% less [1
      14C]linoleic acid (18:2n-6) to arachidonic acid (20:4n-6), 95% less [3
      14C]tetracosatetraenoic acid (24:4n-6) to docosapentaenoic acid (22:5n-6), and
      95% less [1-14C]-linolenic acid (18:3n-3) and [3-14C]tetracosapentaenoic acid
      (24:5n-3) to docosahexaenoic acid (22:6n-3) than did normal human skin
      fibroblasts (NF). The only product formed by the DF cultures from [1
      14C]tetradecadienoic acid (14:2n-6) was 18:2n-6. However, they produced 50;-90%
      as much 20:4n-6 as the NF cultures from [1-14C]hexadecatrienoic acid (16:3n-6),
      [1-14C]gamma-linolenic acid (18:3n-6), and [1-14C]dihomo-gamma-linolenic acid
      (20:3n-6), PUFA substrates that contain Delta6 double bonds. DF also contained
      80% more 18:2n-6 and 25% less 20:4n-6. These results suggested that DF are
      deficient in Delta6 desaturation. This was confirmed by Northern blots
      demonstrating an 81;-94% decrease in Delta6-desaturase mRNA content in the DF
      cultures, whereas the Delta5-desaturase mRNA content was reduced by only 14%.
      This is the first inherited abnormality in human PUFA metabolism shown to be
      associated with a Delta6-desaturase deficiency. Furthermore, the finding that the
      18- and 24-carbon substrates are equally affected suggests that a single enzyme
      carries out both Delta6 desaturation reactions in human PUFA metabolism.

PMID- 11290822
TI  - Oleic acid uptake and binding by rat adipocytes define dual pathways for cellular
      fatty acid uptake.
AB  - Oleic acid (OA) uptake by rat adipocytes and the proportions of intracellular
      unesterified [3H]OA and its 3H-labeled esters were determined over 300 s. Uptake
      was linear for 20;-30 s, with rapid esterification indicating entry into normal
      metabolic pathways. Initial rates of OA uptake and its binding to plasma
      membranes were studied over a spectrum of oleic acid:bovine serum albumin (BSA)
      ratios, and expressed as functions of unbound OA concentrations calculated with
      both the 1971 OA:BSA association constants of Spector, Fletcher, and Ashbrook and
      more recent constants (e.g., the 1993 constants of Richieri, Anel, and
      Kleinfeld), which generate concentrations 10- to 100-fold lower. In either case,
      uptake was the sum of saturable and linear processes, with > or =90% occurring
      via the saturable pathway when the OA:BSA molar ratio was within the physiologic
      range (0.5;-3.0). Within this range, rate constants for saturable transmembrane
      influx (k(s)), calculated from both sets of constants, were similar (2.9 s(-1))
      and were 10- to 30-fold faster than those for nonsaturable uptake (k(ns) = 0.26;
      0.10 s(-1), t1/2 = 2.7;-6.6 s, based on the constants of Spector et al. and
      Richieri et al., respectively). The rate of oleic acid flip-flop into rat
      adipocytes (k(ff) = 0.16 +/- 0.02 s(-1), t1/2 = 4.3 +/- 0.5 s), computed from
      published data, was similar to k(ns). Thus, OA uptake occurs by both a saturable
      mechanism and passive flip-flop. This conclusion is independent of the OA:BSA
      association constants used to analyze the experimental measurements.

PMID- 11290823
TI  - Alpha-tocopherol decreases CD36 expression in human monocyte-derived macrophages.
AB  - Cholesterol-laden macrophages are the hallmark of atherogenesis. The class B
      scavenger receptor, CD36, binds oxidized low density lipoprotein (OxLDL), is
      found in atherosclerotic lesions, and is upregulated by OxLDL. We tested the
      effects of alpha-tocopherol (AT) enrichment of human monocyte-derived macrophages
      on CD36 expression and cholesteryl ester accumulation. Monocytes isolated from
      normal volunteers were cultured into macrophages. Macrophages were enriched
      overnight with various doses of AT (25, 50, and 100 microM). LDL from normal
      volunteers was oxidized or acetylated (AcLDL) and incubated with macrophages for
      48 h at a concentration of 50 or 100 microg/ml. CD36 expression was assessed by
      flow cytometry. Quantitative analysis of scavenger receptor class A (SR-A)
      activity was performed with 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanide perchlorate (DiI)-labeled LDL. CD36 expression was
      maximal after 8;-10 days of culture. AT (> or =50 microM) significantly decreased
      CD36 expression upregulated by OxLDL and AcLDL (P < 0.01). Other antioxidants
      (beta- or gamma-tocopherol) or protein kinase C inhibitors failed to decrease
      CD36 expression. Concomitantly, DiI-AcLDL and DiI-OxLDL uptake was significantly
      decreased after AT treatment (P < 0.001). Cholesteryl ester accumulation was
      significantly decreased after AT enrichment (AcLDL + AT, 77% inhibition; OxLDL +
      AT, 42% inhibition). In conclusion, AT decreases both CD36 and SR-A expression
      and cholesteryl ester accumulation in human macrophages. This provides additional
      scientific support for the antiatherogenic properties of AT.

PMID- 11290824
TI  - Decreased stability of the M54 isoform of paraoxonase as a contributory factor to
      variations in human serum paraoxonase concentrations.
AB  - There are considerable variations in serum concentrations of the high density
      lipoprotein (HDL)-associated enzyme, paraoxonase (PON), which is an important
      determinant of the antioxidant capacity of HDL. The present study examined the
      hypothesis that differences in the stability of isoforms arising from the coding
      region L54M polymorphism could contribute to such variations. A model system was
      developed using transfected Chinese hamster ovary cells to secrete recombinant
      PON corresponding to human L or M isoforms. The recombinant peptides exhibited
      the molecular properties of human serum PON. They formed complexes with
      lipoproteins in culture medium, notably binding to apolipoprotein A-I-containing
      particles. The enzymatic properties of the recombinant isoforms were comparable
      to those of human serum PON. The recombinant M isoform lost activity more rapidly
      and to a greater extent than the recombinant L isoform [26.0 +/- 3.0% vs. 14.0 +/
      1.0% (phenylacetate substrate) and 36.1 +/- 2.0% vs. 19.3 +/- 2.0% (paraoxon
      substrate) over 96 h (P < 0.01)] in medium containing fetal calf serum or PON
      free human serum. Addition of a protease inhibitor resulted in retention of
      activity by both isoforms. Parallel results were obtained in incubation studies
      of human serum from donors homozygous LL or MM for the L54M polymorphism. Enzyme
      activity was lost more rapidly and to a greater extent from MM than LL sera (P <
      0.01). A parallel loss of PON peptide mass was also observed, with a
      significantly greater loss from MM homozygotes (P < 0.001). It corresponded to
      the appearance of a smaller molecular mass band on SDS-PAGE analysis. Direct
      analysis of the proteolytic effect using HDL isolated from homozygotes and
      incubated with purified kallikrein confirmed the greater loss of activity from MM
      homozygotes and the protective effect of proteolysis inhibitor. The results
      provide evidence for lesser stability of the M54 isoform of PON, apparently
      involving greater susceptibility to proteolysis. It provides one mechanism to
      explain variations in serum levels of PON and has implications for the
      antioxidant capacity of HDL.

PMID- 11290825
TI  - The lipid-mobilizing effect of atrial natriuretic peptide is unrelated to
      sympathetic nervous system activation or obesity in young men.
AB  - We recently demonstrated that natriuretic peptides and especially the atrial
      natriuretic peptide (ANP) are powerful lipolytic agents on isolated human fat
      cells. To search for a possible influence of obesity on ANP responsiveness, we
      compared the lipolytic effects of human ANP (h-ANP) on isolated subcutaneous
      abdominal adipose tissue (SCAAT) fat cells from young healthy lean and obese men.
      The lipid-mobilizing effects of an intravenous infusion of h-ANP was studied, as
      well as various metabolic and cardiovascular parameters that were compared in the
      same subjects. h-ANP (50 ng/min/kg) was infused iv for 60 min. Microdialysis
      probes were inserted in SCAAT to measure modifications of the extracellular
      glycerol concentrations during h-ANP infusion. Spectral analysis of blood
      pressure and heart rate oscillations that were recorded using digital
      photoplethysmography were used to assess changes in autonomic nervous system
      activity. h-ANP induced a marked and similar increase in glycerol and
      nonesterified fatty acids, and a weak increase in insulin plasma levels in lean
      and obese men. Plasma norepinephrine concentrations rose similarly during h-ANP
      infusion in lean and obese men. The effects of h-ANP infusion on the autonomic
      nervous system were similar in both groups, with an increase in the spectral
      energy of the low-frequency band of systolic blood pressure variability and a
      decrease in the spectral energy of the high-frequency band of heart rate. In
      SCAAT, h-ANP infusion increased extracellular glycerol concentration and
      decreased blood flow similarly in both groups. The increase in extracellular
      glycerol observed during h-ANP infusion was not modified when 0.1 mM propranolol
      was added to the microdialysis probe perfusate to prevent beta-adrenoceptor
      activation. These data show that ANP is a potent lipolytic hormone independent of
      the activation of the sympathetic nervous system, and that obesity did not modify
      the lipid-mobilizing effect of ANP in young obese subjects.

PMID- 11290826
TI  - A new synthetic class A amphipathic peptide analogue protects mice from diet
      induced atherosclerosis.
AB  - Several synthetic class A peptide analogues have been shown to mimic many of the
      properties of human apo A-I in vitro. A new peptide [acetyl
      (AspTrpLeuLysAlaPheTyrAspLysValPheGluLysPheLysGluPhePhe)-NH2; 5F], with increased
      amphipathicity, was administered by intraperitoneal injection, 20 microg/day for
      16 weeks, to C57BL/6J mice fed an atherogenic diet. Mouse apo A-I (MoA-I) (50
      microg/day) or phosphate-buffered saline (PBS) injections were given to other
      mice as controls. Total plasma cholesterol levels and lipoprotein profiles were
      not significantly different between the treated and control groups, except that
      the mice receiving 5F or MoA-I had lower high density lipoprotein (HDL)
      cholesterol when calculated as a percentage of total cholesterol. No toxicity or
      production of antibodies to the injected materials was observed. When HDL was
      isolated from high fat diet-administered mice injected with 5F and presented to
      human artery wall cells in vitro together with human low density lipoprotein
      (LDL), there were substantially fewer lipid hydroperoxides formed and
      substantially less LDL-induced monocyte chemotactic activity than with HDL from
      PBS-injected animals. Injection of human apo A-I produced effects similar to 5F
      on lipid peroxide formation and LDL-induced monocyte chemotactic activity, but
      injection of MoA-I was significantly less effective in reducing lipid
      hydroperoxide formation or lowering LDL-induced monocyte chemotactic activity.
      Mice receiving peptide 5F had significantly less aortic atherosclerotic lesion
      area compared with mice receiving PBS, whereas lesion area in mice receiving MoA
      I was similar to that of the PBS-injected animals. This is the first in vivo
      demonstration that a model class A amphipathic helical peptide has
      antiatherosclerotic properties. We conclude that 5F inhibits lesion formation in
      high fat diet-administered mice by a mechanism that does not involve changes in
      the lipoprotein profile, and may have potential in the prevention and treatment
      of atherosclerosis.

PMID- 11290827
TI  - Specificity of the lipid-binding domain of apoC-II for the substrates and
      products of lipolysis.
AB  - Functional similarities between colipase and apolipoprotein C-II (apoC-II) in
      activating lipases suggest that apoC-II may, like colipase, preferentially
      interact with interfaces containing the substrates and products of lipolysis. To
      test this hypothesis, the binding of a peptide comprising residues of the
      cofactor implicated in lipid binding, apolipoprotein C-II(13-56), and, to a
      lesser extent, apoC-II, to monomolecular lipid films was characterized. The
      lipids used were a diacylphosphatidylcholine, a diacylglycerol, and a fatty acid.
      The peptide had an affinity for the argon-buffer interface and for all lipids
      consistent with a dissociation constant of <10 nM. Changes in surface pressure
      accompanying peptide binding were comparable to those reported for native apoC-II
      and indicate peptide miscibility with each of the lipids tested. The capacity of
      the surfaces to accommodate the peptide decreased with increasing lipid
      concentration in the interface, indicating competition between lipid and peptide
      for interfacial occupancy. At a lipid acyl chain density of 470 pmol/cm2, or 35
      A2 per acyl chain, a lower limit of peptide adsorption was reached with all
      lipids. The limiting level of adsorption to phosphatidylcholine was only 1
      pmol/cm2 compared with 6;-7 pmol/cm2 for fatty acid and diacylglycerol. Similar
      results were obtained with apoC-II. The difference in the extent of protein
      adsorption to lipid classes suggests that the distribution of apoC-II among
      lipoproteins will depend on their lipid composition and surface pressure.

PMID- 11290828
TI  - In vivo interactions of apoA-II, apoA-I, and hepatic lipase contributing to HDL
      structure and antiatherogenic functions.
AB  - Studies with mice have revealed that increased expression of apolipoprotein A-II
      (apoA-II) results in elevations in high density lipoprotein (HDL), the formation
      of larger HDL, and the development of early atherosclerosis. We now show that the
      increased size of HDL results in part from an inhibition of the ability of
      hepatic lipase (HL) to hydrolyze phospholipids and triglycerides in the HDL and
      that the ratio of apoA-I to apoA-II determines HDL functional and antiatherogenic
      properties. HDL from apoA-II transgenic mice was relatively resistant to the
      action of HL in vitro. To test whether HL and apoA-II influence HDL size
      independently, combined apoA-II transgenic/HL knockout (HLko) mice were examined.
      These mice had HDL similar in size to apoA-II transgenic mice and HLko mice,
      suggesting that they do not increase HDL side by independent mechanisms.
      Overexpression of apoA-I from a transgene reversed many of the effects of apoA-II
      overexpression, including the ability of HDL to serve as a substrate for HL.
      Combined apoA-I/apoA-II transgenic mice exhibited significantly less
      atherosclerotic lesion formation than did apoA-II transgenic mice. These results
      were paralleled by the effects of the transgenes on the ability of HDL to protect
      against the proinflammatory effects of oxidized low density lipoprotein (LDL).
      Whereas nontransgenic HDL protected against oxidized LDL induction of adhesion
      molecules in endothelial cells, HDL from apoA-II transgenic mice was
      proinflammatory. HDL from combined apoA-I/apoA-II transgenic mice was equally as
      protective as HDL from nontransgenic mice. Our data suggest that as the ratio of
      apoA-II to apoA-I is increased, the HDL become larger because of inhibition of
      HL, and lose their antiatherogenic properties.

PMID- 11290829
TI  - Enhanced dietary fat clearance in postobese women.
AB  - The objective of this study was to examine the postprandial response to an
      exogenous fat source in eight weight-stable postobese subjects (2;-3 years after
      gastric bypass) and eight matched control women, using a stable isotope,
      [13C]oleate. After a high fat breakfast meal (1,062 cal, 67% fat), [13C]oleate in
      triglyceride (TG)-rich lipoproteins (Sf >400 and Sf 20;-400) and nonesterified
      fatty acids (NEFA), and 13C in breath CO2, were monitored over 8 h. There were no
      differences in resting energy expenditure, thermic effect of food,
      carbohydrate/fat oxidation ratio, breath 13CO2 enrichment, or fecal fat content
      between postobese and control subjects. Postprandially, there was no difference
      in S(f) 20;-400 TG or NEFA, but postobese subjects had lower Sf >400 incremental
      area under the curve (AUC) (- 33%, P < 0.0025) and glucose [P < 0.01 by repeated
      measures analysis of variance (RM ANOVA)]. Postprandial 13C in Sf >400 TG
      returned to fasting levels 4 h earlier in postobese subjects and was lower than
      in control subjects at 4 and 6 h (P < 0.05 by RM ANOVA). The greatest difference
      was in the [13C]NEFA profiles. In control subjects [13C]NEFA increased markedly
      over 8 h; postobese subject [13C]NEFA remained close to fasting nonenriched
      values, and was strikingly lower than in control subjects (72% lower by AUC, P <
      0.0001 by RM ANOVA). Finally, postobese subjects tended to have lower
      postprandial insulin (P < 0.01, 4 h), lower postprandial acylation-stimulating
      protein, and lower fasting leptin (-46%, P < 0.02). This study demonstrates clear
      metabolic differences in exogenous dietary fat partitioning in postobese women.
      These findings are compatible with an increased efficiency of dietary fat storage
      and suggest one possible mechanism for promotion of weight regain in postobese
      individuals.

PMID- 11290830
TI  - Fetal baboons convert 18:3n-3 to 22:6n-3 in vivo. A stable isotope tracer study.
AB  - Using [13C]-tracers and direct fetal doses, we show for the first time that the
      fetal primate converts alpha-linolenic acid (18:3) to docosahexaenoic acid (22:6)
      in vivo, and we estimate the relative bioefficacy of the two substrates for brain
      22:6 accretion. Pregnant female baboons consumed a diet free of long chain
      polyunsaturates (LCP), with n-6/n-3 ratio of 10/1. In the third trimester of
      pregnancy (normal gestation = 182 days), they were instrumented with chronic
      indwelling catheters in the maternal femoral artery and the fetal jugular artery.
      Doses of either [U-13C]-18:3 (18:3*, n = 3) or [U-13C]-22:6 (22:6*, n = 2) were
      administered directly to the fetus. Blood was collected from fetus and mother,
      and the fetus was taken by cesarean section when electromyographic activity
      indicated that parturition was imminent. Fetal liver, brain, retina, and retinal
      pigment epithelium (RPE) were collected, and (13)C fatty acids determined. In
      18:3*- dosed animals, labeled n-3 LCP were detected in fetal plasma at 1 day post
      dose and peaked at 2;-3 days; brain 22:6* was constant at 3, 5, and 9 days post
      dose, at 0.57 +/- 0.03 percent of dose (%Dose). In 22:6*- dosed animals, brain
      22:6* was similar at 3 and 9 days post-dose (4.64 +/- 0.43%Dose). From these
      data, we estimate that preformed 22:6 in the fetal bloodstream is 8-fold more
      efficacious for brain 22:6 accretion than is 18:3. Retina 22:6* was stable at
      about 0.0008%Dose from 3 to 9 days in 18:3-dosed animals, but RPE 22:6* dropped
      over the period; brain results were consistent with these observations. Liver
      showed about 0.5%Dose in 22:6* and in intermediary n-3 fatty acid metabolites
      20:5* and 22:5* at 3 days post-dose, and declined afterward. Back-transfer of
      labeled fatty acids to the maternal bloodstream was measurable but not sufficient
      to compromise the quantitative conversion data in fetuses. We conclude 1) primate
      fetuses have the capacity to convert 18:3 to 22:6 in vivo; 2) fetal brain 22:6*
      as %Dose plateaus by 3 days post-dose; 3) fetal plasma 22:6 is about 8-fold more
      effective as a substrate for brain 22:6 accretion compared with 18:3; and 4) the
      fetal liver is likely to be an important site of 18:3 to 22:6 conversion.

PMID- 11290831
TI  - Identification of platelet-activating factor as the inflammatory lipid mediator
      in CCl4-metabolizing rat liver.
AB  - Unmitigated oxidative stress is deleterious, as epitomized by CCl4 intoxication.
      In this well-characterized model of free radical-initiated damage, liver
      metabolism of CCl4 to CCl3. causes lipid peroxidation, F-ring isoprostane
      formation, and pathologic leukocyte activation. The nature of the mediator that
      couples oxidation to the hepatotoxic inflammatory response is uncharacterized. We
      found that oxidatively modified phosphatidylcholines were present in the livers
      of CCl4-exposed rats and not in livers from control animals, that CCl4 metabolism
      generated lipids that activated 293 cells stably transfected with the human
      platelet-activating factor (PAF) receptor, and that this PAF-like activity was
      formed as rapidly as isoprostane-containing phosphatidylcholine (iPC) during
      oxidation. iPC and the PAF-like activity also had similar chromatographic
      properties. The potential for iPC activation of the PAF receptor has been
      unexplored, but we conclude that iPC themselves did not activate the PAF
      receptor, as phospholipase A1 hydrolysis completely destroyed iPC, but none of
      the PAF-like bioactivity. Oxidatively fragmented phospholipids are potent
      agonists of the PAF receptor, but mass spectrometry characterized PAF as the
      major inflammatory component coeluting with iPC. Oxidatively fragmented
      phospholipids and iPC are markers of free radical generation in CCl4-intoxicated
      liver, but PAF generation by activated hepatic cells generated the inflammatory
      agent.

PMID- 11290832
TI  - Impact of hydrogenated fat on high density lipoprotein subfractions and
      metabolism.
AB  - Relative to saturated fatty acids, trans-fatty acids/hydrogenated fat-enriched
      diets have been reported to increase low density lipoprotein (LDL) cholesterol
      levels and either decrease or have no effect on high density lipoprotein (HDL)
      cholesterol levels. To better understand the effect of trans-fatty
      acids/hydrogenated fat on HDL cholesterol levels and metabolism, 36 subjects
      (female, n = 18; male, n = 18) were provided with each of three diets containing,
      as the major sources of fat, vegetable oil-based semiliquid margarine,
      traditional stick margarine, or butter for 35-day periods. LDL cholesterol levels
      were 155 +/- 27, 168 +/- 30, and 177 +/- 32 mg/dl after subjects followed the
      semiliquid margarine, stick margarine, and butter-enriched diets, respectively.
      HDL cholesterol levels were 43 +/- 10, 42 +/- 9, and 45 +/- 10 mg/dl,
      respectively. Dietary response in apolipoprotein (apo) A-I levels was similar to
      that in HDL cholesterol levels. HDL(2) cholesterol levels were 12 +/- 7, 11 +/-
      6, and 14 +/- 7 mg/dl, respectively. There was virtually no effect of dietary fat
      on HDL3 cholesterol levels. The dietary perturbations had a larger effect on
      particles containing apoA-I only (Lp A-I) than apoA-I and A-II (Lp A-I/A-II).
      Cholesterol ester transfer protein (CETP) activity was 13.28 +/- 5.76, 15.74 +/-
      5.41, and 14.35 +/- 4.77 mmol x h(-1) x ml(-1), respectively. Differences in
      CETP, phospholipid transfer protein activity, or the fractional esterification
      rate of cholesterol in HDL did not account for the differences observed in HDL
      cholesterol levels. These data suggest that the saturated fatty acid component,
      rather than the trans- or polyunsaturated fatty acid component, of the diets was
      the putative factor in modulating HDL cholesterol response.

PMID- 11290833
TI  - Sequestration of aggregated LDL by macrophages studied with freeze-etch electron
      microscopy.
AB  - The detailed morphology of macrophages involved in the uptake and intracellular
      processing of low density lipoprotein (LDL) and, ultimately, formation of
      macrophage-derived foam cells of atherosclerotic lesions has long fascinated
      investigators. This study examined localization of LDL in subcellular
      compartments of macrophage-derived intimal foam cells in cardiac valves isolated
      from rabbits by diet-induced hypercholesterolemia and, as an in vitro model of
      formation of foam cells, in cultured human monocyte-macrophages incubated for 2;
      120 h with aggregated LDL produced by vortexing or phospholipase C lipolysis. The
      quasi-three-dimensional morphology of macrophages involved in endocytosis was
      preserved by ultrarapid freezing and freeze-etch microscopy in conjunction with
      thin-section electron microscopy. This approach produced unique images of
      subcellular compartments in human monocyte-macrophages involved in the uptake and
      processing of aggregated LDL with a clarity not previously reported. Three
      dimensional ultrastructural analyses revealed a complex network of coated and
      uncoated vesicles, surface-connected saclike compartments, and
      endosomal/lysosomal compartments including the labyrinth of vesicular/tubular
      lysosomes all enmeshed in the microtubular, microfilament cytoskeletal network.
      These dynamic views of subcellular structures at the high resolution of the
      electron microscope provide an additional framework to better understand how
      lipoprotein particles are transported into, and processed within, macrophages
      during foam cell formation in atherogenesis.

PMID- 11290834
TI  - Apolipoprotein L gene family: tissue-specific expression, splicing, promoter
      regions; discovery of a new gene.
AB  - Previously we identified and cloned the cDNA for a new protein, apolipoprotein L
      (apoL), present in plasma and mainly associated with large high density
      lipoprotein particles. Using 5' rapid amplification of cDNA ends, RT-PCR and
      comparison with three Human Genome Project and three expressed sequence tag
      sequences, we have characterized the gene for apoL and for three additional,
      highly homologous proteins that constitute a new family of proteins that display
      no homology with previously described apolipoproteins. The genes for all four
      proteins, apoL-I, apoL-II, apoL-III, and apoL-IV, are located at chromosome
      22q12.1-13.1 within a 127,000-bp region. The apoL-I gene is in the opposite
      orientation to the other three. All four genes have TATA-less promoters, which
      contain putative sterol regulatory elements, suggesting that transcription of
      these genes may be coordinated with that of the low density lipoprotein receptor
      and genes in pathways involving the synthesis of triglycerides and cholesterol.
      The gene family has a consensus eight-exon structure with alternative splice
      sites that could produce as many as eight distinct gene products. The apoL-II and
      apoL-III genes have alternative transcriptional start sites as a result of
      additional 5' exons. apoL-I, apoL-II, and apoL-III are expressed to the highest
      degree in the lung. Other tissues with high expression are the pancreas,
      prostate, spleen, liver, and placenta. Four clustered common polymorphisms, three
      of which altered the protein sequence, were found in apoL-I, all in linkage
      disequilibrium, and describing two haplotypes: the more common
      Lys166/Ile244/Lys271 and the rarer Glu166/Met244/Arg271.

PMID- 11290835
TI  - Evaluation of Lp[a] and other independent risk factors for CHD in Asian Indians
      and their USA counterparts.
AB  - Conventional risk factors for coronary heart disease (CHD) do not completely
      account for the observed increase in premature CHD in people from the Indian
      subcontinent or for Asian Indians who have immigrated to the USA. The objective
      of this study was to determine the effect of immigration to the USA on plasma
      levels of lipoprotein [a] (Lp[a]) and other independent risk factors for CHD in
      Asian Indians. Three subject groups were studied: group 1, 57 subjects living in
      India and diagnosed with CHD (CHD patients); group 2, 46 subjects living in India
      and showing no symptoms of CHD (control subjects); group 3, 206 Asian Indians
      living in the USA. Fasting blood samples were drawn to determine plasma levels of
      triglyceride (TG), total cholesterol (TC), low density lipoprotein [LDL
      cholesterol (LDL-Chol)], high density lipoprotein [HDL cholesterol (HDL-Chol)],
      apolipoprotein B-100 (apoB-100), and Lp[a]. Apolipoprotein [a] (apo[a]) size
      polymorphism was determined by immunoblotting. Plasma TG, apoB-100, and Lp[a]
      concentrations were higher in CHD patients than in control and USA groups. CHD
      patients had higher levels of TC and LDL-Chol and lower HDL-Chol than control
      subjects. However, the USA population had higher levels of TC, LDL-Chol, and apoB
      100 and lower HDL-Chol than control subjects. Plasma Lp[a] levels were inversely
      correlated with the relative molecular weight of the more abundant of each
      subject's two apo[a] isoforms (MAI), and CHD patients showed higher frequencies
      of lower relative molecular weights among MAI. Our observed changes in lipid
      profiles suggest that immigrating to the USA may place Asian Indians at increased
      risk for CHD. This study suggests that elevated plasma Lp[a] confers genetic
      predisposition to CHD in Asian Indians, and nutritional and environmental factors
      further increase the risk of CHD. This is the first report implicating MAI size
      as a predictor for development of premature CHD in Asian Indians. Including
      plasma Lp[a] concentration and apo[a] phenotype in screening procedures may
      permit early detection and preventive treatment of CHD in this population.

PMID- 11290836
TI  - Composition and ultrastructure of size subclasses of normal human peripheral
      lymph lipoproteins: quantification of cholesterol uptake by HDL in tissue fluids.
AB  - Peripheral lymph lipoproteins have been characterized in animals, but there is
      little information about their composition, and none about their ultrastructure,
      in normal humans. Therefore, we collected afferent leg lymph from 16 healthy
      males and quantified lipids and apolipoproteins in fractions separated by high
      performance-size exclusion chromatography. Apolipoprotein B (apoB) was found
      almost exclusively in low density lipoproteins. The distribution of apoA-I,
      particularly in lipoprotein A-I (LpA-I) without A-II particles, was shifted
      toward larger particles relative to plasma. The fractions containing these
      particles were also enriched in apoA-II, apoE, total cholesterol, and
      phospholipids and had greater unesterified cholesterol-to-cholesteryl ester
      ratios than their counterparts in plasma. Fractions containing smaller apoA-I
      particles were enriched in phospholipid. Most apoA-IV was lipid poor or lipid
      free. Most apoC-III coeluted with large apoA-I-containing particles. Electron
      microscopy showed that lymph contained discoidal particles not seen in plasma.
      These findings support other evidence that high density lipoproteins (HDL)
      undergo extensive remodeling in human tissue fluid. Total cholesterol
      concentration in lymph HDL was 30% greater (P < 0.05) than could be explained by
      the transendothelial transfer of HDL from plasma, providing direct confirmation
      that HDL acquire cholesterol in the extravascular compartment. Net transport
      rates of new HDL cholesterol in the cannulated vessels corresponded to a mean
      whole body reverse cholesterol transport rate via lymph of 0.89 mmol (344
      mg)/day.

PMID- 11290837
TI  - Key regulatory oxysterols in liver: analysis as delta4-3-ketone derivatives by
      HPLC and response to physiological perturbations.
AB  - A number of oxysterols have been implicated in metabolic regulation. Key among
      these are (24S),25-epoxycholesterol and (24S)-hydroxycholesterol, high affinity
      ligands for the nuclear transcription factor liver X receptor alpha; 27
      hydroxycholesterol, a bile acid synthetic intermediate; and 25
      hydroxycholesterol, which has been used to study regulation of lipid metabolism
      by the sterol regulatory element-binding protein family of transcription factors.
      Investigation of the physiological importance of these compounds in vivo has been
      hampered by lack of analytical methods to reproducibly and accurately determine
      their concentrations in tissues. This article describes a method designed to
      determine quantitatively the amounts of these important side-chain oxysterols by
      derivatization to the Delta4-3-ketones followed by high performance liquid
      chromatography. The method was validated with known standards and then was used
      to determine the concentrations of these oxysterols in rodent liver under various
      physiological conditions. All four oxysterols were present in the picogram per
      milligram protein range and have distinct subcellular distributions and responses
      to physiological perturbations in vivo.

PMID- 11290838
TI  - Oxidation and base-catalyzed elimination of the saccharide portion of GSLs having
      very different polarities.
AB  - Glycosphingolipids (GSLs), present in cell membranes, participate in a variety of
      biological functions. Although their exact role(s) may not be understood, it has
      been shown that 1) embryos lacking glucosylceramide synthase activity do not
      develop normally, 2) GSLs can affect neuritogenesis, and 3) they can function as
      receptors for some pathogens. To study the role of the saccharide portion of a
      GSL in any of these functions, it is necessary to either isolate it from the
      intact GSL or synthesize it. Because syntheses are more complex, modifications
      were made to the oxidation/elimination procedure previously described for the
      isolation of the saccharide portion of GM1 and GD1a to enable it to be used with
      GSLs of varying polarity. The key is to use a mixture of GSLs that differ in
      polarity. This appears to eliminate problems encountered when purified GSLs such
      as sulfatide or GT1b are used.

PMID- 11290839
TI  - Quantitative determination of phospholipid compositions by ESI-MS: effects of
      acyl chain length, unsaturation, and lipid concentration on instrument response.
AB  - Electrospray ionization-mass spectrometry (ESI-MS) is a very promising tool for
      the analysis of phospholipid compositions, but is hampered by the fact that not
      all molecular species are detected with equal efficiency. We studied this and
      other issues that need to be taken into account to obtain truly quantitative
      compositional data. The key findings were as follows: First, the instrument
      response for both saturated and unsaturated phospholipid species decreased with
      increasing acyl chain length. This effect became increasingly prominent with
      increasing overall lipid concentration. Second, the degree of acyl chain
      unsaturation also had a significant effect on instrument response. At the highest
      concentration studied (10 pmol/microl), polyunsaturated species gave 40% higher
      intensity than the fully saturated ones. The effect of unsaturation diminished
      and nearly disappeared with progressive dilution. Third, the instrument response
      for the different head group classes varied markedly depending on the infusion
      solvent used. Notably, inclusion of ammonia in the infusion solvent eliminated
      sodium adduct formation in the positive ion mode, thus greatly simplifying the
      interpretation of the spectra. The fact that instrument response is dependent on
      many structural features, overall lipid concentration, solvent composition, and
      instrument settings makes it necessary to include several internal standards for
      each phospholipid class to obtain accurate data. Preferably, both unsaturated and
      saturated standards should be used. Finally, we quantified the major phospholipid
      classes of BHK cells using ESI-MS. The data agreed closely with those obtained
      with thin-layer chromatography and phosphorus analysis. This study indicates that
      quantitative compositional data can be obtained with ESI-MS, provided that proper
      attention is paid to experimental details, particularly the choice of internal
      standards.

PMID- 11290841
TI  - A genome-wide search for genes that relate to a low level of response to alcohol.
AB  - BACKGROUND: The low level of response (LR) to alcohol is genetically influenced
      in both humans and animals, and a low LR is a characteristic of offspring of
      alcoholics that has been reported to predict alcoholism 10 and 15 years later.
      The genes that contribute to a low LR have not yet been identified. METHODS: A 12
      item questionnaire that measures LR, the Self Rating of the Effects of Alcohol
      (SRE) instrument, was filled out by 745 individuals from the Collaborative Study
      on the Genetics of Alcoholism (COGA) for whom genetic material was available.
      These subjects were genotyped by using 336 markers with an average heterozygosity
      of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and
      qualitative nonparametric, sib-pair analyses were carried out for the SRE measure
      related to early drinking experiences. RESULTS: Correlations of SRE scores across
      related individuals were significant and between 0.16 and 0.22 for most values,
      compared with nonsignificant correlations of 0.03 or less among unrelated
      individuals. Linkage analyses performed by using the FIRST 5 variables (first
      five times alcohol is consumed) identified four chromosomal regions with lod
      scores > or = 2.0 whose maximum was also near a marker. One of these chromosomal
      regions previously was linked to alcohol dependence in the COGA sample.
      CONCLUSIONS: These data document the familial nature of a low LR to alcohol as
      measured by the SRE and suggest several chromosomal regions that might contribute
      to the phenomenon.

PMID- 11290842
TI  - Mismatch negativity in subjects at high risk for alcoholism.
AB  - BACKGROUND: Evidence from P300 studies in both alcohol-dependent and high-risk
      (HR) individuals suggests that the reduced P300 amplitudes that often
      characterize these individuals may reflect a deficit in inhibition
      (hyperexcitability) in the central nervous system. In this context, the mismatch
      negativity (MMN) was investigated in the male and female HR offspring of alcohol
      dependent fathers and a mixed-sex, low-risk (LR) control group. METHODS: As
      subjects read popular materials, they received a random sequence of 500
      binaurally presented tones of 600 Hz and 1600 Hz. The designation of the rare
      stimulus (n = 60 trials) and frequent stimulus (n = 440 trials) was alternated
      across subjects. Recordings of MMN were made from 61 electrodes; risk group
      comparisons were restricted to the five frontal midline electrodes: Fpz, Afz, Fz,
      Fcz, and Cz. The MMN was obtained by calculating the integral of the area under
      the curve for both the frequent and rare waveforms over an interval from 100 to
      190 msec and then subtracting the former from the latter. RESULTS: The primary
      observation was that MMN responses in the HR group were significantly larger than
      those in the LR group. In addition, both LR and HR individuals manifested
      differential responses to the rare and frequent stimuli, and MMN responses in
      both groups were largest at Fcz and smallest at Fpz. DISCUSSION: The results
      indicate that individuals at high risk for alcoholism differ
      electrophysiologically from LR controls. These differences were manifested as
      larger magnitudes of the MMN. The findings suggest the possibility that as
      measured by the MMN, individuals at high risk for alcoholism may be characterized
      by a deficit in inhibition (excessive neural excitation). The presence of these
      preexisting central nervous system states may lead to ethanol use for self
      medication, which then may facilitate the development of both tolerance to and
      dependence on ethanol.

PMID- 11290843
TI  - The synthesis and secretion of fatty acid ethyl esters from HepG2 cells are
      stimulated by lipoproteins and albumin.
AB  - BACKGROUND: Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of
      ethanol produced by the esterification of fatty acids and ethanol. FAEEs have
      been implicated as mediators of ethanol-induced organ damage in vivo and in
      vitro. They are detectable in the blood and in many organs after ethanol
      ingestion, and on this basis they are useful markers of ethanol intake in living
      patients as well as subjects at autopsy. FAEEs found in human plasma after
      ethanol ingestion bind to lipoproteins and albumin. METHODS: In this study, we
      used a hepatoblastoma cell model (HepG2) to determine if lipoproteins or albumin
      stimulates the synthesis and/or secretion of FAEEs from HepG2 cells. Because
      FAEEs have been shown to decrease HepG2 cellular proliferation and protein
      synthesis, their removal from cells potentially could reestablish normal cell
      activity. HepG2 cells were incubated with 100 mM ethanol and 6 nM 3H oleic acid
      to generate 3H-FAEEs within the cells. Dose response and time course studies were
      performed by using low density lipoproteins, high density lipoproteins, and
      albumin as FAEE acceptors. RESULTS: The results indicate that FAEEs are extracted
      efficiently by each of these FAEE carriers and that FAEE synthesis also is
      stimulated by the addition of FAEE carriers to the extracellular medium.
      CONCLUSION: These observations indicate that lipoproteins and albumin can extract
      ethyl esters from HepG2 cells and thereby may limit alcohol-induced liver damage.

PMID- 11290844
TI  - Effects of acamprosate on ethanol-seeking and self-administration in the rat.
AB  - BACKGROUND: Acamprosate (calcium acetyl homotaurinate) has been used clinically
      to treat relapse in alcoholics. In rats, it has been shown to decrease ethanol,
      but not water, self-administration after ethanol deprivation. METHODS: To further
      investigate the effect of acamprosate on reinforced behaviors in rats, the
      present experiment used: (1) both ethanol and sucrose reinforcer solutions to
      better assess the distinct effects of acamprosate on ethanol-directed behaviors,
      and (2) an operant model that procedurally separates the "cost" to begin drinking
      from consuming the reinforcer solutions to dissociate the effects of acamprosate
      on appetitive versus consummatory processes. In daily sessions (5 days/week),
      rats (n = 6/group) were trained to make 30 lever-press responses to gain access
      for 20 min to a sipper tube containing either ethanol (10%) or sucrose (3%).
      After stable responding, acamprosate treatment was given. Three doses were tested
      (50, 100, and 200 mg/kg/injection, intraperitoneally), one dose per week. Each
      week, a total of four injections were given (21 and 2 hr before the operant
      sessions over 2 consecutive days). RESULTS: At these doses, acamprosate had no
      effect on the measures of appetitive responding for either solution. However, all
      doses reliably decreased ethanol consumption on the 2nd day of treatment (from an
      average of 0.83 to 0.63 g/kg). Analysis of the pattern of ethanol consumption
      showed that the effects of acamprosate occurred after the onset of a normal
      pattern of intake, as measured by lick rate and size of the initial bout of
      drinking, which suggested that acamprosate is most effective when combined with
      the pharmacological effects of ethanol. Sucrose intake was unaffected by all
      acamprosate treatments, which indicated that the treatment effects were specific
      to ethanol and not due to a general decrease in consummatory behavior.
      CONCLUSIONS: Overall, these results suggest that acamprosate is effective at
      reducing total ethanol intake, but may not reliably alter subjects propensity to
      begin a drinking bout as measured by this model. However, whether this applies to
      the clinical use of acamprosate, where other types of reinforcement may also
      precipitate relapse drinking, is not certain.

PMID- 11290845
TI  - Ethanol-induced increased surface-localized fibrinolytic activity in cultured
      human endothelial cells: kinetic analysis.
AB  - BACKGROUND: Moderate alcohol consumption is associated with reduced risk for
      coronary heart disease and this cardioprotection may be due, in part, to
      increased fibrinolysis. We have previously demonstrated that low concentrations
      of ethanol (0.1%, v/v) induce the short-term (<1 hr) and sustained, long-term (24
      hr) increase in surface-localized fibrinolytic activity; it up-regulates t-PA, u
      PA, and the candidate plasminogen receptor (PmgR), annexin II, and gene
      transcription in cultured human umbilical vein endothelial cells (HUVECs). These
      studies describe the short- and long-term effects of low concentrations of
      ethanol on the kinetics of cell-bound 125I-labeled Glu-plasminogen (Glu-Pmg)
      activation by receptor (R)-bound t-PA, resulting in increased fibrinolytic
      activity in cultured HUVECs. METHODS: Live cultured HUVECs were incubated with
      varying concentrations of Glu-Pmg (0.25-2 /M) and ethanol (0.025-0.1%, v/v) (in
      the presence of Aprotinin and alpha2-antiplasmin) and the direct activation of
      cell-bound 125I-labeled Glu-Pmg quantitated by measurement of 125I-labeled Mr 20
      kDa plasmin light-chain, after reduction/SDS-PAGE. The effects of ethanol on '25I
      labeled Glu-Pmg and t-PA ligand binding were determined by Scatchard analysis
      (Bmax, sites/cell). RESULTS: Cell-bound t-PA (endogenous/exogenous) activation of
      cultured HUVEC-bound 125I-labeled Glu-Pmg (short- and long-term) obeyed Michaelis
      Menten kinetics, both in the absence/presence of low ethanol, as shown by
      Lineweaver-Burke plot analysis. In the short-term, ethanol (at 0.1%) increased
      the Vmax (2.5-fold), kcat (2-fold) and the apparent kcat/Km (4-fold),
      commensurate with a significant decrease in the apparent Km (6-fold) and increase
      in '25I-labeled Glu-Pmg ligand binding, Bmax (2-fold). In the long-term, ethanol
      increased the Vmax (2- to 3-fold), kcat (2.5-fold), apparent kcat/Km (5-fold),
      and Bmax (2-fold) for 125I-labeled Glu-Pmg ligand binding, without significantly
      affecting the apparent K . CONCLUSIONS: Low concentrations of ethanol induce the
      short- versus long-term increase in surface-localized fibrinolytic activity in
      cultured HUVECs via different mechanisms. Short-term effects may be mediated by
      ethanol-induced membrane conformational changes that simultaneously facilitate
      increased surface-localized HUVEC PmgR availability and fibrinolytic
      protein/receptor interactions, resulting in the increased affinity of t-PA for
      Glu-Pmg and the accelerated activation of Glu-Pmg (increased Bmax, decreased
      apparent Km). The long-term effects may be attributed primarily to the ethanol
      induced increased availability of both newly synthesized t-PA and PmgR and,
      hence, the accelerated activation of Glu-Pmg (increased Bmax)

PMID- 11290846
TI  - Altered emotional perception in alcoholics: deficits in affective prosody
      comprehension.
AB  - BACKGROUND: Affective prosody is a nonlinguistic aspect of language that conveys
      emotion and attitude during discourse. It is a dominant function of the right
      hemisphere. Because skills associated with the right hemisphere have been found
      to be impaired in alcoholics, this study explored the possibility that affective
      prosodic functioning may be sensitive to the effects of alcohol due to heavy
      persistent drinking or prenatal exposure. METHODS: Subjects were aged 25 to 58
      years. Twenty-nine men and three women who met DSM-IV criteria for an alcohol use
      disorder with a median of 39 days of sobriety, 11 men with a probable history of
      fetal alcohol exposure (FAexp), and 41 age-matched control subjects of both sexes
      were tested by using the Aprosodia Battery. This instrument assesses affective
      prosodic comprehension (APC) across a range of verbal articulatory demands.
      RESULTS: The alcoholic group scored 2 SD below the control mean, and the FAexp
      group scored -5 SD regardless of whether they had ever been diagnosed with
      alcohol abuse. Despite their poor performance on APC, alcoholic and FAexp groups
      performed similarly to the control group on vocabulary, abstract reasoning, and
      an index of cognitive impairment that used the Shipley Institute of Living Scale.
      Multiple regression analyses that used nine alcohol use variables to model APC
      resulted in four significant contributors to the effect. These regressors were
      related to early exposure to ethanol and chronicity of alcohol abuse.
      CONCLUSIONS: Alcoholics and FAexp subjects were significantly less accurate at
      APC compared with controls. These alcohol-exposed subjects appear to be deficient
      in the ability to understand emotional valence in the speech of others, which
      results in errors of judgment that may impair social interactions.

PMID- 11290847
TI  - Induction of steady-state blood alcohol levels: application to the study of
      within-session alcohol tolerance in rats.
AB  - BACKGROUND: The study of within-session alcohol tolerance in the rat has been
      hampered by methodological difficulties related to the measurement of dependent
      variables at predictable blood alcohol concentrations (BAC) during a single
      session of alcohol exposure. This study characterizes a method for maintaining
      steady-state blood alcohol levels over several hours in the rat, referred to as
      the "alcohol clamp." METHODS: Wistar rats were implanted with an indwelling
      catheter in the carotid artery for blood sampling and another in the external
      jugular vein for alcohol infusion. To clamp BAC at a predetermined level, rats
      first were infused with a priming dose of alcohol to establish the desired or
      "target" BAC, followed by a continuous infusion of alcohol at a rate equal to
      that of alcohol metabolism in the rat. This maintained BAC at a constant level
      over time. BACs of 100, 200, or 300 mg% were maintained over several hours in
      separate groups of rats. The alcohol clamp was applied to the study of acute
      (within-session) alcohol tolerance in rats selectively bred for high and low
      alcohol drinking. Alcohol-induced hypothermia was used to index tolerance, and
      within-session alcohol tolerance was defined as a return of body temperature
      toward baseline during the course of the alcohol infusion while BAC was
      maintained at a constant level. RESULTS: The continuous alcohol infusion
      procedure maintained BAC in a steady state throughout the 3 hr alcohol infusion
      session at each of the three target BAC levels. Alcohol infusion induced a drop
      in body temperature, followed by a return of temperature toward baseline during
      the course of infusion, which indicated the development of within-session alcohol
      tolerance. CONCLUSIONS: The continuous alcohol infusion procedure (alcohol clamp)
      maintained BAC in a steady state, both within and between subjects, across a wide
      range of blood alcohol levels. The alcohol clamp appears to be a useful tool for
      subsequent studies of within-session alcohol tolerance in the rat.

PMID- 11290848
TI  - Acute effects of ethanol on behavior of adolescent rats: role of social context.
AB  - BACKGROUND: First experiences with alcohol in humans occur predominantly in
      adolescence, and to a large extent the attractiveness of alcohol at this age is
      based on its ability to facilitate certain forms of social behavior (social
      facilitation). Adolescence is strongly marked by a focus on peer relationships,
      and the social nature of the situation plays an important role in responsiveness
      to alcohol. Peer-directed social activity of adolescent rats may be a valuable
      experimental model for the study of ethanol-induced changes in social behavior
      and assessment of the role of the social context in responsiveness to ethanol.
      METHOD: In the present study we used a modified dyad social interaction test to
      characterize acute effects of ethanol on different forms of social behavior
      (social investigation, contact behavior, and play) and social motivation
      (preference/avoidance of a peer) in adolescent rats. Ethanol effects on behavior
      directed toward a peer were compared with those induced by exposure to an
      inanimate novel object. RESULTS: In the social context, the effects of ethanol
      were dose-dependent and biphasic. Low doses of ethanol (0.25-0.75 g/kg) produced
      apparent social facilitation (increased social activity and enhanced social
      preference), whereas higher doses (3 and 4 g/kg) caused social inhibition
      (decreased social activity and avoidance of a peer). This pattern was not
      observed for a nonsocial stimulus: Although overall activity in the nonsocial
      context was suppressed by 2 and 3 g/kg of ethanol, 0.5 g/kg of ethanol did not
      activate overall activity directed to the inanimate object. CONCLUSIONS: These
      findings demonstrate that the social nature of the testing situation plays an
      important role in responsiveness to alcohol in adolescence, especially to its
      activating effects. The results suggest also that the study of ethanol effects on
      social behavior of adolescent rats may be an effective tool for the study of
      adolescent alcohol use and abuse.

PMID- 11290849
TI  - Effect of neuropeptide Y (NPY) on oral ethanol intake in Wistar, alcohol
      preferring (P), and -nonpreferring (NP) rats.
AB  - BACKGROUND: Neuropeptide Y (NPY) deficient mice consume more ethanol than
      controls, whereas NPY over-expressing mice consume less ethanol than controls.
      Thus, ethanol drinking may be inversely associated with NPY activity. To
      determine whether exogenously administered NPY would alter ethanol intake, two
      experiments were conducted. METHODS: A within-subject design was used with
      intracerebroventricular (ICV) administration of NPY or artificial cerebral spinal
      fluid (aCSF) into the lateral ventricles. Infusions were separated by 2 to 7
      days. In experiment 1, male Wistar rats (n = 10) were tested for the effects of
      NPY on an intake of 5% sucrose or 8% (w/v) ethanol during daily 2-hr testing
      periods with food and water available at all other times. In experiment 2, male
      alcohol-preferring (P) and alcohol-nonpreferring (NP) rats (n = 8/line) were
      tested for the effects of NPY on 8% (w/v) ethanol intake. RESULTS: In experiment
      1, NPY (5, 10, 20 microg) significantly increased sucrose intake relative to aCSF
      baseline in Wistar rats, a finding consistent with previous observations of the
      orexigenic effects of the peptide. However, NPY (10 microg) did not alter ethanol
      intake in Wistar rats. In experiment 2, NPY (5 and 10 microg) significantly
      decreased ethanol intake in P rats, but not in NP rats. CONCLUSION: The reduction
      in ethanol intake seen with the P rats is consistent with the postulated negative
      relationship between NPY activity and ethanol intake. The lack of effect of NPY
      on ethanol intake in Wistar and NP rats may be related to the lower baseline
      levels of ethanol intake in these rats or to differential central nervous system
      basal NPY activity or sensitivity to the peptide.

PMID- 11290850
TI  - Ethanol as a reinforcer in the newborn's first suckling experience.
AB  - BACKGROUND: Recent evidence suggests that human infants prefer alcohol-flavored
      milk when fed through a bottle. Animal models also indicate a surprising
      predisposition for neonatal and infant rats to voluntarily and willingly ingest
      ethanol. These findings suggest high susceptibility to the reinforcing properties
      of ethanol early in ontogeny. METHODS: A surrogate nipple technique-a highly
      effective tool for investigation of the reinforcing properties of different
      fluids-was applied in the present study. Tests of ethanol reinforcement were
      accomplished in terms of two basic paradigms of Pavlovian conditioning. In one
      paradigm, the conditioned stimulus (CS) was the surrogate nipple, and in the
      other, the CS was a novel odor. RESULTS: Newborn rats showed sustained attachment
      to the nipple providing 5% ethanol, and later reproduced this behavioral pattern
      toward the empty nipple (CS alone). Ingestion of ethanol yielding appetitive
      reinforcement was accompanied by detectable blood alcohol concentrations, with
      most in the range of 20-30 mg/dl. The reinforcing efficacy of ethanol was also
      confirmed in the classical olfactory conditioning paradigm: following pairing
      with intraoral ethanol infusions, the odor (CS) alone elicited sustained
      attachment to an empty nipple. Females showed better olfactory conditioning with
      low concentrations of ethanol, whereas males were effectively more conditioned to
      high concentrations. Although there were no reinforcing consequences of
      intraperitoneally injected ethanol [as an unconditioned stimulus (US)] when a
      neutral odor was the CS, when paired with ingestion of water from a nipple, the
      injection of ethanol had a reinforcing effect. CONCLUSIONS: The present series of
      experiments revealed ethanol reinforcement in the newborn rat. Two varieties of
      Pavlovian conditioning established that ethanol can serve as an effective US, and
      hence reinforcer, in such a way as to increase the approach and responsiveness
      toward stimuli paired with that US, indicating appetitive reinforcement.

PMID- 11290851
TI  - Long-term follow-up of a high school alcohol misuse prevention program's effect
      on students' subsequent driving.
AB  - BACKGROUND: Alcohol-related injuries, particularly motor vehicle, are an
      important cause of adolescent mortality. School-based alcohol prevention programs
      have not been evaluated in terms of driving outcomes. This study examined the
      effects on subsequent driving of a high school-based alcohol prevention program.
      METHODS: The Alcohol Misuse Prevention Study included a randomized test of the
      effectiveness of an alcohol misuse prevention curriculum conducted among 4,635
      10th-grade students. Students were assigned to intervention (n = 1,820) or
      control (n = 2,815) groups and were followed for an average of 7.6 years after
      licensure, which typically occurred during or shortly after 10th grade. Outcomes
      examined included alcohol-related and other serious offenses, and at-fault,
      single-vehicle, and alcohol-related crashes. RESULTS: Only serious offenses
      (which included alcohol-related) had a significant treatment effect
      (statistically marginal) after we adjusted for sex, age, race, alcohol
      use/misuse, family structure, presence of prelicense offenses, age of driver
      licensure, and parental attitudes toward teen drinking. The effect was found only
      during the first year of licensure (estimated adjusted relative risk = 0.80,
      confidence interval = 0.63-1.01). Two first-year serious offense interactions
      were found. The positive effect was strongest among the largest subgroup of
      students, those who were drinking less than one drink per week on average before
      the curriculum, compared with those who drank more than one drink per week (p =
      0.009). The effect was also stronger for the small subgroup of students whose
      parents had not expressed disapproval of teens' drinking, compared with those
      whose parents had disapproved (p = 0.004). CONCLUSIONS: These findings suggest
      that a high school-based alcohol prevention program can positively affect
      subsequent driving, particularly that of students who do not use alcohol
      regularly. The results highlight the need to start prevention efforts early and
      extend them beyond the initial exposure to driving. Programs should incorporate
      the differing backgrounds of the students.

PMID- 11290852
TI  - Course of DSM-IV alcohol dependence in a community sample: effects of parental
      history and binge drinking.
AB  - BACKGROUND: The role of positive family history in the etiology of alcohol
      dependence has been demonstrated repeatedly but little is known about the effect
      of this risk factor on the chronicity of alcohol dependence once it has begun.
      METHODS: We studied the effects of parental and sibling history in conjunction
      with frequency of binge drinking in a sample of 169 community residents who met
      criteria for DSM-IV alcohol dependence at the baseline interview. Subjects were
      re-interviewed approximately 1 year later and the status of their alcohol
      dependence disorders (remitted or chronic) was determined. RESULTS: Parental
      history of alcoholism was significantly related to chronicity of alcohol
      dependence, as was frequency of binge drinking. CONCLUSIONS: Failure to find an
      effect for family history on chronicity would have suggested that the effect was
      transient, perhaps interacting with time-limited environmental vulnerability. The
      finding of a positive relationship between family history and chronicity suggests
      that the relationship between familial/ genetic background and alcohol dependence
      is stable.

PMID- 11290853
TI  - Reduced folate carrier: tissue distribution and effects of chronic ethanol intake
      in the micropig.
AB  - BACKGROUND: Folate deficiency is common in alcoholic patients, in part due to
      abnormal transport across membranes relevant to folate homeostasis. The reduced
      folate carrier (RFC) transports monoglutamyl folates across tissue membranes and
      could be affected by chronic exposure to ethanol. The micropig model is suitable
      to study the effect of alcoholism on RFC and folate transport across membranes.
      METHODS: The membrane transport of [3H]-folic acid was measured by a vacuum
      filtration method in jejunal brush border (JBB), liver plasma membrane (LPM), and
      kidney brush border (KBB) membranes vesicles from micropigs fed control or 40%
      ethanol diets for 12 months. RFC transcripts were analyzed by reverse
      transcription polymerase chain reaction in jejunal mucosa, liver, and kidney from
      the same animals. RESULTS: When we compared results from three relevant membranes
      in control animals, the transport of [3H]-folic acid was highest in LPM, 3-fold
      lower in KBB (p < 0.001), and 6-fold lower in JBB (p < 0.001). The concentration
      of RFC transcripts per total RNA was greatest in liver, followed by kidney and
      jejunum. The transport of [3H]-folic acid by JBB vesicles from chronic ethanol
      fed animals exhibited 2-fold lower Km and Vmax (p < 0.05), whereas there was no
      ethanol effect on the Vmax of [3H]-folic acid transport by LPM or KBB. RFC
      transcript levels were 10-fold lower in jejunal mucosa from ethanol-fed animals
      than in control-fed animals (p < 0.005). CONCLUSIONS: Although our findings
      demonstrate different RFC transcript amounts and transport efficiencies among
      tissues, the present studies suggest that chronic ethanol exposure decreases the
      intestinal absorption of folic acid by altering the expression of RFC and
      consequently its transport kinetics in JBB. These findings provide a mechanism
      for the clinical finding of reduced folic acid absorption in chronic alcoholics.

PMID- 11290854
TI  - Acetaldehyde production and other ADH-related characteristics of aerobic bacteria
      isolated from hypochlorhydric human stomach.
AB  - BACKGROUND: Acetaldehyde is a known local carcinogen in the digestive tract in
      humans. Bacterial overgrowth in the hypochlorhydric stomach enhances production
      of acetaldehyde from ethanol in vivo after alcohol ingestion. Therefore,
      microbially produced acetaldehyde may be a potential risk factor for alcohol
      related gastric and cardiac cancers. This study was aimed to investigate which
      bacterial species and/or groups are responsible for acetaldehyde formation in the
      hypochlorhydric human stomach and to characterize their alcohol dehydrogenase
      (ADH) enzymes. METHODS: After 7 days of treatment with 30 mg of lansoprazole
      twice a day, a gastroscopy was performed on eight volunteers to obtain
      hypochlorhydric gastric juice. Samples were cultured and bacteria were isolated
      and identified; thereafter, their acetaldehyde production capacity was measured
      gas chromatographically by incubating intact bacterial suspensions with ethanol
      at 37 degrees C. Cytosolic ADH activities, Km values, and protein concentration
      were determined spectrophotometrically. RESULTS: Acetaldehyde production of the
      isolated bacterial strains (n = 51) varied from less than 1 to 13,690 nmol of
      acetaldehyde/10(9) colony-forming units/hr. ADH activity of the strains that
      produced more than 100 nmol of acetaldehyde/10(9) colony-forming units/hr (n =
      23) varied from 3.9 to 1253 nmol of nicotinamide adenine dinucleotide per minute
      per milligram of protein, and Km values for ethanol ranged from 0.65 to 116 mM
      and from 0.5 to 3.1 M (high Km). There was a statistically significant
      correlation (r = 0.64, p < 0.001) between ADH activity and acetaldehyde
      production from ethanol in the tested strains. The most potent acetaldehyde
      producers were Neisseria and Rothia species and Streptococcus salivarius, whereas
      nearly all Stomatococcus, Staphylococcus, and other Streptococcus species had a
      very low capacity to produce acetaldehyde. CONCLUSIONS: This study demonstrated
      that certain bacterial species or groups that originate from the oral cavity are
      responsible for the bulk of acetaldehyde production in the hypochlorhydric
      stomach. These findings provide new information with the respect to the local
      production of carcinogenic acetaldehyde in the upper digestive tract of
      achlorhydric human subjects.

PMID- 11290855
TI  - Mice that lack corticotropin-releasing factor (CRF) receptors type 1 show a
      blunted ACTH response to acute alcohol despite up-regulated constitutive
      hypothalamic CRF gene expression.
AB  - BACKGROUND: The purpose of this work was to determine the influence of acute
      alcohol treatment, injected intraperitoneally, on the hypothalamic-pituitary
      adrenal axis of mice that lack type 1 receptor for corticotropin-releasing factor
      (CRFR1). METHODS: CRFR1-deficient (CRFR1-/-), heterozygous (CRFR1+/-), and wild
      type (CRFR1+/+) mice were generated and maintained under standard conditions.
      Homozygous, heterozygous, and wild-type offspring were identified by polymerase
      chain reaction analysis of tail DNA. Experiments were performed on 9- to 16-week
      old male and female mice. All blood samples were obtained by rapid decapitation
      of conscious mice conducted between 10 AM-12 PM. Blood sample collection was
      completed within 20 to 30 sec of disturbing the animals, and all samples were
      terminal. Preliminary experiments were conducted to determine the time-course of
      the ACTH and hypothalamic responses to alcohol in all three groups of mice, and a
      single time point (30 min and 2 hr, respectively), corresponding to peak
      responses, was chosen to measure the corresponding parameters in all subsequent
      studies. RESULTS: In vehicle-injected animals, basal ACTH and corticosterone
      levels were statistically comparable in heterozygotes and mice with a null allele
      for the CRFR1 gene, although values of this latter hormone were slightly lower in
      the mutants. Alcohol (4.0 g/kg) elicited the expected significant (p < 0.01)
      increase in plasma ACTH and corticosterone levels in heterozygous mice. These
      responses were virtually abolished or markedly decreased, respectively, in CRFR1
      deficient animals. As previously reported, constitutive CRF mRNA levels were
      elevated in the paraventricular nucleus (PVN) of the hypothalamus in mice that
      lacked CRFR1, compared to wild-type control mice. Interestingly, this was not the
      case for transcripts of the immediate early gene NGFI-B. When measured 2 hr after
      alcohol, PVN NGFI-B gene expression was significantly (p < 0.01) increased in
      both control and mutant mice, as were CRF mRNA levels in mutant mice, but the
      hypothalamic responses of the mutants were larger (p < 0.01) than those of the
      control mice. This difference may be due, at least in part, to the lack of
      steroid feedback in the mutants. CONCLUSION: These results indicate that although
      the intraperitoneal injection of alcohol remains capable of eliciting PVN CRF
      neuronal activation in mice that lack CRFR1, the ACTH and corticosterone
      responses are significantly blunted, a phenomenon believed to be due to the lack
      of CRFR1 in the pituitary of these animals.

PMID- 11290856
TI  - Enhanced antioxidant activity after chlorination of quercetin by hypochlorous
      acid.
AB  - BACKGROUND: Several epidemiological studies indicate that moderate consumption of
      red wine decreases both the incidence and mortality associated with
      cardiovascular disease. Quercetin and rutin (quercetin-3-rutinoside) are
      polyphenols present in relatively large concentrations in red wine and may play a
      role in this cardioprotective phenomenon. The precise mechanisms of
      cardioprotection remain unclear but may involve the action of these polyphenols
      as antioxidants, which attenuate the tissue injury that results from the
      production of proinflammatory oxidants such as hypochlorous acid (HOCl). METHODS:
      To study the interaction of these polyphenols with proinflammatory oxidants, we
      mixed quercetin or rutin with HOCl (0-150 microM) and analyzed the reaction
      products by high-performance liquid chromatography, mass spectrometry, and
      nuclear magnetic resonance. RESULTS: Stable mono- and dichlorinated derivates
      were detected for both quercetin and the glycoside derivative, rutin, which
      suggests that both the conjugated and unconjugated forms of quercetin reacted
      with HOCl similarly. Chlorination of quercetin occurred only at two sites, and
      the derivates (6-chloroquercetin, 6,8-dichloroquercetin) were more potent
      antioxidants toward oxidative modification of low-density lipoproteins and ABTS
      radical formation than the unmodified form. CONCLUSIONS: These data suggest that
      under certain pathological conditions in vivo (e.g., inflammation), flavonols may
      be converted to chlorinated derivates, which exhibit an enhanced antioxidant
      potential and thereby play a role in cardioprotection.

PMID- 11290857
TI  - Prolonged ethanol treatment enhances lipopolysaccharide/phorbol myristate acetate
      induced tumor necrosis factor-alpha production in human monocytic cells.
AB  - BACKGROUND: Ethanol (EtOH) is known to alter host immune responses and cytokine
      production. Acute EtOH exposure can suppress tumor necrosis factor (TNF)-alpha
      production, which attenuates pulmonary defense against infection. Previous
      studies in our laboratory show that acute EtOH inhibited TNF-alpha production by
      a posttranscriptional process, namely suppression of TNF-alpha-converting, enzyme
      mediated, ectodomain shedding. However, chronic EtOH has been shown to augment
      TNF-alpha production, and this has been associated with EtOH-induced liver
      injury. To further characterize this paradoxical effect of EtOH on TNF-alpha
      production, we developed an in vitro model by using Mono Mac 6 cells, a human
      monocytic cell line. METHODS: Mono Mac 6 cells were treated with EtOH (0-75 mM)
      for 1 to 7 days. TNF-alpha production was induced by lipopolysaccharide and
      phorbol myristate acetate and quantitated by enzyme-linked immunosorbent assay.
      Generation of reactive oxygen species (ROS) was assayed by using a specific
      fluorogenic reagent. RESULTS: Acute EtOH initially inhibited
      lipopolysaccharide/phorbol myristate acetate-induced TNF-alpha production in Mono
      Mac 6 cells. However, during chronic EtOH exposure, this inhibition was reversed
      gradually over time. By day 6 after EtOH treatment, Mono Mac 6 cells demonstrated
      significant up-regulation of TNF-alpha production. Moreover, chronic EtOH induced
      the generation of ROS in these Mono Mac 6 cells. Scavenging ROS by
      Mn(III)tetrakis(1-methyl-4pyridyl)porphyrin pentachloride and N-acetyl-L-cysteine
      attenuated chronic EtOH-enhanced TNF-alpha production. CONCLUSION: These results
      suggest that ROS induction is involved in EtOH-enhanced TNF-alpha production by
      monocytes. This study also provides insight into the mechanisms of alteration of
      TNF-alpha production in different EtOH exposure settings.

PMID- 11290858
TI  - Inhibition of hematopoietic progenitor cell proliferation by ethanol in human
      immunodeficiency virus type 1 tat-expressing transgenic mice.
AB  - BACKGROUND: A number of hematological abnormalities are associated with both
      human immunodeficiency virus type 1 (HIV-1) infection and alcohol abuse. There is
      little information on how alcohol abuse might further influence the survival and
      growth of hematopoietic progenitors in HIV-infected individuals in the presence
      of immune system abnormalities and anti-HIV drugs. Because there is evidence that
      viral transactivator Tat itself can induce hematopoietic suppression, in this
      study we examined the role of ethanol as a cofactor in transgenic mice that
      expressed HIV-1 Tat protein. METHODS: Tat transgenic mice and nontransgenic
      littermates were given ethanol (20% v/v) and the anti-HIV drug 3'-azido-3'
      deoxythymidine (AZT; 1 mg/ml) in drinking water. Immunosuppression in mice was
      induced by weekly intraperitoneal injections of anti-CD4 antibody. Hematopoiesis
      was examined by erythroid colony forming unit (CFU-E) and granulocyte/macrophage
      colony-forming unit (CFU-GM) assays of the bone marrow progenitor cells. RESULTS:
      Administration of ethanol for 7 weeks resulted in a 50% decrease in the
      proliferative capacity of CFU-E- and CFU-GM-derived progenitors from transgenic
      mice compared with that of ethanol-treated nontransgenic controls. Similar
      decreases also were observed in transgenic mice treated with AZT or a combination
      of AZT and ethanol. Furthermore, ethanol and AZT were significantly more toxic to
      the granulopoietic progenitors (40-50% inhibition) than to the erythropoietic
      progenitors (10-20% inhibition) in Tat transgenic mice. Although a 10 day
      exposure of Tat transgenic and nontransgenic mice to a combination of ethanol and
      AZT had no suppressive effect on the erythropoietic and granulopoietic progenitor
      cells, there was a marked decrease (40-60%) in CFU-GM in mice made
      immunodeficient by CD4+ T-lymphocyte depletion. The ethanol-treated Tat
      transgenic mice but not the nontransgenic litter-mates also showed a significant
      decrease (25%) in CFU-GM. CONCLUSION: Our in vivo study strongly suggests that
      ethanol ingestion in HIV-1-infected individuals, particularly those on
      antiretroviral drugs, might increase bone marrow toxicity and contribute to HIV-1
      associated hematopoietic impairment.

PMID- 11290859
TI  - A rodent model of alcoholic heart muscle disease and its evaluation by
      echocardiography.
AB  - BACKGROUND: Transthoracic echocardiography was used in a rodent animal model to
      determine whether long-term alcohol consumption (8 and 12 months) was associated
      with the development of a dilated cardiomyopathy. We also investigated whether
      alcohol-induced changes in cardiac structure corresponded to activation of the
      renin-angiotensin system and the natriuretic peptide (NP) system. METHODS: Male
      rats received either the Lieber-DeCarli liquid alcohol diet (EtOH) (9%v/v) (n =
      8) or control diet (CON) (n = 8). Echocardiography (echo) was used to determine
      left-ventricular (LV) dimensions, and isolated heart studies (Langendorff and
      atrium) were used to assess ex vivo contractility. Plasma and tissue angiotensin
      I converting enzyme (ACE) activity was measured. Gene expression, plasma, and
      tissue levels of the NPs were determined by northern blot analysis and
      radioimmunoassay, respectively. RESULTS: After 8 months of alcohol consumption,
      there was a trend for the end diastolic dimension, end systolic dimension, and LV
      mass to be greater in the 8 month EtOH group compared with the CON group.
      However, after 12 months of alcohol consumption, significant increases were found
      between the groups in several echo parameters. Tissue ACE activity (nmoles/min/mg
      protein) was greater in the 12 month EtOH group compared with the 12 month CON
      and 8 month EtOH group (p < 0.05). We found no differences between groups in gene
      expression (messenger RNA), plasma, and tissue levels of the NPs. CONCLUSIONS:
      Echocardiography revealed that 8 to 12 months of alcohol consumption was
      associated with the development of a dilated cardiomyopathy. However, this was
      not preceded by an increase in tissue ACE activity, and these changes occurred in
      the absence of increased plasma and LV tissue levels of the NPs.

PMID- 11290860
TI  - Ethanol consumption and the susceptibility of mice to Listeria monocytogenes
      infection.
AB  - BACKGROUND: It is well known that excessive alcohol consumption correlates with
      increased infectious disease. However, the molecular microbiological and
      immunological bases for ethanol-induced alterations in host defense are largely
      unknown. METHODS: To study the effect of alcohol consumption on the pathogenesis
      of intracellular bacteria, we examined the relative susceptibility of alcohol-fed
      mice to a virulent strain of Listeria monocytogenes. RESULTS: Based on lethal
      dose 50% determinations, survival curve analysis, and bacterial burden, alcohol
      consumption did not increase the susceptibility of C57BL/6, BALB/c, or A/J mice
      to systemic infection by strain EGD. Mice fed an ethanol-containing liquid diet
      showed slightly reduced susceptibility to Listeria. Alcohol consumption modestly
      decreased bacterial numbers in the spleen but not the liver. We also found that
      mice fed a typical solid diet were more sensitive to EGD infection than were
      animals fed a control liquid-containing diet. CONCLUSIONS: This study indicates
      that alcohol consumption may not always increase infectious disease progression.

PMID- 11290861
TI  - The problem of college drinking: insights from a developmental perspective.
AB  - This article represents the proceedings of a symposium at the 2000 RSA Meeting in
      Denver, Colorado. John Schulenberg and Jennifer L. Maggs were Organizers. Stephen
      W. Long was Chair and provided opening remarks. The presentations were: (1) I'm
      not a drunk, just a college student: Binge drinking during college as a
      developmental disturbance, by John Schulenberg; (2) Course of alcohol use
      disorders during college, by Kenneth J. Sher; (3) How do students experience
      alcohol and its effects? Positive versus negative expectancies and consequences,
      by Jennifer L. Maggs; and (4) Brief intervention in the context of developmental
      trends in college drinking, by G. Alan Marlatt. Critique and commentary were
      provided by Robert A. Zucker.

PMID- 11290862
TI  - Ethanol enhances GABAA receptor function in short sleep and long sleep mouse
      brain membranes.
AB  - BACKGROUND: SS and LS mice have been used to explore the genetic and
      neurochemical bases for differences in sensitivity to ethanol. The present study
      investigated the effects of ethanol on GABAA receptor function in microsacs from
      these genotypes. The purpose was to test a key element of the hypothesis that
      differences between these lines in sensitivity to ethanol-induced enhancement of
      GABAA receptor function underlie their selected differences in sensitivity to
      ethanol-induced loss of righting reflex (LORR). METHODS: The effects of ethanol
      on GABA-activated 36Cl- uptake in brain membranes (microsacs) isolated from male
      SS and LS mice were tested using a chloride flux filtration assay. RESULTS:
      Ethanol significantly enhanced GABA-activated 36Cl- uptake in SS microsacs at
      concentrations of 100-300 mM. Ethanol did not significantly affect GABA-activated
      chloride uptake in this preparation at concentrations of 25 and 50 mM. Ethanol
      significantly enhanced GABA-activated 36Cl- uptake in LS microsacs at
      concentrations of 25-100 mM, but not at 200 mM. CONCLUSION: The present studies
      are the first to show a statistically significant effect of ethanol on GABA
      activated chloride uptake in both SS and LS mice with a clear difference between
      the genotypes in threshold. The relative threshold differences between SS and LS
      microsacs in sensitivity to ethanol indicate that selection for resistance to
      ethanol-induced LORR in SS mice has shifted the ethanol-GABAA receptor
      concentration-response curve to the right. The findings add key evidence that
      supports a cause-effect relationship between sensitivity to ethanol-induced
      potentiation of GABAA receptor function and genetically determined sensitivity to
      ethanol's behavioral effects.

PMID- 11290863
TI  - Ras biochemistry and farnesyl transferase inhibitors: a literature survey.
AB  - Over the last decades, knowledge on the genetic defects involved in tumor
      formation and growth has increased rapidly. This has launched the development of
      novel anticancer agents, interfering with the proteins encoded by the identified
      mutated genes. One gene of particular interest is ras, which is found mutated at
      high frequency in a number of malignancies. The Ras protein is involved in signal
      transduction: it passes on stimuli from extracellular factors to the cell
      nucleus, thereby changing the expression of a number of growth regulating genes.
      Mutated Ras proteins remain longer in their active form than normal Ras proteins,
      resulting in an overstimulation of the proliferative pathway. In order to
      function, Ras proteins must undergo a series of post-translational modifications,
      the most important of which is farnesylation. Inhibition of Ras can be
      accomplished through inhibition of farnesyl transferase, the enzyme responsible
      for this modification. With this aim, a number of agents, designated farnesyl
      transferase inhibitors (FTIs), have been developed that possess antineoplastic
      activity. Several of them have recently entered clinical trials. Even though
      clinical testing is still at an early stage, antitumor activity has been
      observed. At the same time, knowledge on the biochemical mechanisms through which
      these drugs exert their activity is expanding. Apart from Ras, they also target
      other cellular proteins that require farnesylation to become activated, e.g.
      RhoB. Inhibition of the farnesylation of RhoB results in growth blockade of the
      exposed tumor cells as well as an increase in the rate of apoptosis. In
      conclusion, FTIs present a promising class of anticancer agents, acting through
      biochemical modulation of the tumor cells.

PMID- 11290864
TI  - Granulocyte colony stimulating factors: how different are they? How to make a
      decision?
AB  - Two granulocyte colony stimulating factors (G-CSFs) are available for clinical
      use in Europe: filgrastim (Neupogen) and lenograstim (Granocyte). The purpose of
      this literature review is to study how they differ, the clinical implications of
      these differences (especially in terms of efficacy) and the economic impact of
      these differences. From a chemical point of view the two molecules are not
      identical. Their amino acid sequence is different and one is glycosylated,
      whereas the other is not. The important question to ask is what these structural
      differences mean for the patient. It appears that glycosylation has important
      consequences in terms of efficacy. Several recent comparative studies, both in
      vitro and in vivo, in animals and in humans, reinforce this idea which was often
      shared intuitively by physicians. In economical terms, in hospitals where the
      exact dosages are used (150 microg/m2 or 19.2 million units (MU)/m2 for
      Granocyte, and 5 microg/kg or 0.5 MU/kg for Neupogen), the choice of G-CSF must
      be made according to the daily cost of treatment which, for an average patient,
      means comparing the price of 325 microg of Neupogen and of 255 microg of
      Granocyte. This is in fact equal to comparing the price per MU of each product.
      In hospitals where one vial per patient per day is used whatever be their weight
      or body surface area, the price per MU and the price per vial should be
      considered together, puting into perspective the potential therapeutic benefit
      for patients, one vial of Granocyte 34 containing more MU than one vial of
      Neupogen 30.

PMID- 11290865
TI  - Phase I and pharmacokinetic study of the orally administered farnesyl transferase
      inhibitor R115777 in patients with advanced solid tumors.
AB  - R115777 is a novel selective inhibitor of farnesyl transferase, an enzyme that is
      involved in the proliferation of the malignant cell type. This study was designed
      to determine the toxicity, maximal tolerated dose and pharmacokinetics of R115777
      when given orally b.i.d. for 28 days followed by 1-2 weeks of rest. Patients with
      advanced solid tumors for whom no standard therapy was available could enter the
      study. The starting dose of R115777 was 200 mg/dose and inter- as well as intra
      patient dose escalations were performed with increments of 100 mg/dose. Nine
      patients entered the study and received in total 23 treatment cycles. A dose of
      300 mg b.i.d. proved feasible with grade 4 neutropenia occurring in one of six
      patients who completed the first treatment cycle. Other toxicities were
      infrequent. Pharmacokinetic analysis demonstrated that peak plasma concentrations
      of 881+/-393 ng/ml were reached within 1-5 h. No accumulation of R115777 was
      observed over a 28-day period. The study was terminated based on these results
      together with the observation from a related phase I study in which higher doses
      of R115777 were associated with the frequent occurrence of grade 3-4
      myelosuppression. We conclude that the recommended dose of R115777 given for 28
      days followed by 1-2 weeks of rest is 300 mg b.i.d. Myelosuppression is the dose
      limiting toxicity.

PMID- 11290866
TI  - Selection of candidates for oral etoposide salvage chemotherapy in heavily
      pretreated breast cancer patients.
AB  - Metastatic breast cancer (MBC) is still in most cases an uncurable disease and
      the main goal of treatment is a good quality of life for these patients.
      Therefore it is very important to select patients who are appropriate candidates
      for the particular salvage chemotherapy (CT) schedule. The aim of our study was
      to assess treatment response to oral etoposide, and to analyze its relationship
      with patients' and disease characteristics. Seventy-five patients with
      bidimensionally measurable MBC were included into our study. For most of the
      patients treatment with etoposide was third-line CT regimen and most of them
      (90%) had been exposed to previous anthracycline-based CT. Etoposide was
      administered orally at a dose of 100 mg/day for 10 days every 3 weeks. The
      overall response rate was 37% (95% CI: 27-50%) with a median time to progression
      (TTP) and survival of 4.5 and 12 months, respectively. Patients with a long
      disease-free interval, predominant soft tissue and bone metastases, and less than
      three metastatic sites responded better to oral etoposide; however, a
      significantly better response was achieved only in those who had responded to
      previous CT (46 versus 19%, p=0.04), especially to anthracyclines (50 versus 17%,
      p=0.016). Response to previous anthracycline-based regimen was the only
      characteristic that significantly influenced TTP (median TTP: 7 versus 2.5
      months, p=0.0066) and survival (median survival: 13.8 versus 5 months, p=0.0072).
      Toxic side effects were generally mild. Salvage CT with oral etoposide is an
      appropriate treatment for patients who respond to previous CT, particularly to
      anthracyclines. It combines a favorable toxicity profile with the major advantage
      of an oral drug administered at home.

PMID- 11290867
TI  - Ifosfamide and mitoxantrone in the treatment of recurrent and/or metastatic
      squamous cell carcinoma of the head and neck.
AB  - A phase II study was performed to assess the safety and efficacy of ifosfamide
      and mitoxantrone in recurrent and/or metastatic squamous cell carcinomas of the
      head and neck. Treatment consisted of ifosfamide 1500 mg/m2 in 1000 ml saline,
      infused over 60 min and mesna 20% of the total dose of ifosfamide in three doses
      for 3 days combined with mitoxantrone 12 mg/m2 given as a short infusion on day
      1. Treatment courses were repeated every 4 weeks until a total of six cycles.
      Twenty-two patients entered this trial, 13 of whom had received chemo- and
      radiation therapy, and nine patients who underwent radiation therapy with or
      without prior surgery. We observed no objective response, with the exception of
      two patients who experienced minor response (reduction of tumor size of 25%). The
      dose-limiting toxicity was myelosuppression with grade 3/4 leukocytopenia in
      seven patients (32%) and grade 3/4 neutropenia in 15 (68%). Severe organ toxicity
      except alopecia (91%) was not observed. Ifosfamide combined with mitoxantrone
      does not improve the therapeutic armentarium in recurrent squamous cell carcinoma
      of the head and neck.

PMID- 11290868
TI  - Unexpected severe myelotoxicity of gemcitabine in pretreated breast cancer
      patients.
AB  - Gemcitabine is a chemotherapeutic agent with proven antitumor effects in
      pancreatic and non-small cell lung cancer; however, studies establishing the
      definite significance in other solid tumors are still in progress. We herein
      present three female patients with advanced breast cancer who received
      gemcitabine as salvage chemotherapy. Gemcitabine at a dose of 1250 mg/m2 was
      scheduled for days 1, 8 and 15 with a subsequent rest for 1 week. However, within
      1 week after the very first administration of gemcitabine myelotoxicity WHO grade
      IV occurred in all patients, leading to discontinuation of therapy. In two
      patients this gemcitabine-induced hematotoxicity could be overcome by means of
      vigorous supportive care, but one patient died after cerebral bleeding due to
      severe thrombocytopenia. We conclude that gemcitabine in heavily pretreated
      breast cancer patients should only be used with extreme caution with special
      focus on platelet counts until solid data from clinical studies for doses and
      schedules are available.

PMID- 11290869
TI  - Preclinical antitumor activity of the azonafide series of anthracene-based DNA
      intercalators.
AB  - The azonafides are a series of anthracene-based DNA intercalators which inhibit
      tumor cell growth in vitro at low nanomolar concentrations and are not affected
      by the multidrug resistance phenomenon (MDR). Prior studies have described
      antitumor efficacy in murine tumor models including L-1210 and P-388 leukemias,
      and B-16 melanoma. The current results extend these cell line observations to
      human tumors tested in the NCI panel of 56 cell lines, in freshly isolated tumors
      tested in colony-forming assays in soft agar and in several animal models. In the
      NCI panel, the overall mean 50% cell kill (LC50) for the unsubstituted azonafide,
      AMP-1, was 10(-5.53) M, with some selectivity noted in melanomas (10(-6.22) M).
      The mean LC50 for the 6-ethoxy substituted analog, AMP-53, was 10(-5.53) M, with
      some selectivity found in non-small cell lung cancer (10(-5.91)) and renal cell
      carcinoma (10(-5.84)). In freshly isolated human tumors tested in soft agar,
      there was marked activity (mean IC50 in microg/ml) for AMP-53 in four cell types:
      breast cancer (0.09), lung cancer (0.06), renal cell carcinomas (0.06) and
      multiple myeloma (0.03). These effects were superior to doxorubicin and to
      several other azonafides, including AMP-1, AMP-104 and the 6-hydroxyethoxy
      derivative, AMP-115. Compound AMP-1 was shown to be superior to amonafide in the
      mammary 16C breast cancer model in B6CF31 mice, but it had little activity in
      Colon-38 nor in M5076 ovarian sarcomas in vivo. Nine azonafides were evaluated in
      the Lewis lung cancer model in C57/bl mice, but only AMP-53 demonstrated
      significant efficacy with a treated/control x 100% (T/C) value of 30%. Because
      AMP-53 demonstrated the greatest breadth of activity, it was then evaluated in
      several human tumor cell lines growing in mice with severe combined
      immunodeficiency disease (SCID). Only three tumors were sensitive (T/C<42%),
      including HL-60 leukemia (T/C=39%), MCF-7 breast cancer (T/C=39%) and A549 non
      small cell lung cancer (T/C=37%). Overall, these results demonstrate that the 6
      ethoxy substituted azonafide, AMP-53, has consistent (in vitro and in vivo)
      experimental antitumor activity in human breast and lung cancer, and could be
      considered for clinical testing in patients with MDR tumors.

PMID- 11290870
TI  - Antitumor activity, optimum administration method and pharmacokinetics of 13,14
      dihydro-15-deoxy-deoxy-Delta7 -prostaglandin A1 methyl ester (TEI-9826)
      integrated in lipid microspheres (Lipo TEI-9826).
AB  - 13,14-Dihydro-15-deoxy-Delta7-prostaglandin A1 methyl ester (TEI-9826), an
      antitumor prostaglandin analog, is a candidate for clinical trial. In the present
      study, we examined its biological stability in vitro, antitumor activity in vitro
      and in vivo, and pharmacokinetics. Although TEI-9826 was rapidly hydrolyzed to
      the carboxylic acid form (TOK-4528), TOK-4528 as well as Delta12-prostaglandin J2
      (PGJ2) were found to be stable in rat, mouse and human serum in vitro. TEI-9826
      exhibited nearly identical or greater potential antitumor activity compared to
      Delta12-PGJ2 and Delta7-PGA1 in vitro against Colon26 tumor cells. Further
      evaluation of TEI-9826 using the 38 human cancer cell lines panel and COMPARE
      analysis suggested that its mode of action is quite different from other
      anticancer agents that are currently used. TEI-9826 was integrated into lipid
      microspheres (Lipo TEI-9826) for dosing. Growth inhibition by Lipo TEI-9826
      against Colon26 tumor inoculated s.c. in mice depended on administration route,
      i.e. at 80 mg/kg, no growth suppressive effect was observed for daily bolus i.v.,
      but significant growth suppressive effect was observed for daily i.p., daily s.c.
      every other day s.c. and 4 times a day continuous (5 min) i.v. These tumor growth
      suppressive effects were cytostatic and the tumor started to regrow at the end or
      a few days after the end of administration. The pharmacokinetic study suggested
      that maintaining the blood level of TEI-9826 and/or TOK-4528 was essential for
      their antitumor effects. These results show that continuous i.v. infusion might
      be the most suitable administration method of Lipo TEI-9826 for clinical trial.

PMID- 11290871
TI  - Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice.
AB  - Prolonging tumor exposure to topoisomerase I inhibitors has been correlated to
      enhance the efficacy of those agents. Lurtotecan, a water-soluble camptothecin
      analog, was formulated as a liposomal drug, NX211, to enhance the delivery of
      drug to tumors. Tumor-bearing mice were treated with either [14C]NX211 containing
      [14C]lurtotecan, [3H]NX211 containing [3H]phosphatidylcholine or [14C]lurtotecan,
      euthanized at selected times post-injection, and tissues, plasma, urine and feces
      were collected. These studies demonstrated that KB tumors of [14C]NX211-treated
      mice had approximately 70-fold greater concentrations of [14C]lurtotecan at 24 h,
      respectively, compared to concentrations of [14C]lurtotecan of the KB tumors of
      [14C]lurtotecan-treated mice. The area under curve (AUC) from 0 to 48 h of
      [14C]lurtotecan for the KB tumors of [14C]NX211-treated animals was over 17-fold
      greater than the AUC of [14C]lurtotecan for the tumors of [14C]lurtotecan-treated
      animals. Treatment with [3H]NX211 demonstrated that the lipid component
      continually accumulated over 24 h in the tissues. HPLC analysis of extracted
      material from tumors of [14C]NX211-treated mice showed that more than 95% of the
      radioactive material was intact [14C]lurtotecan. These findings are one of the
      keys justifying the development of a liposomal formulation of lurtotecan, which
      has the intent to increase tumor exposure and increase antitumor efficacy.

PMID- 11290872
TI  - Sequential gene expression of P-glycoprotein (P-gp), multidrug resistance
      associated protein (MRP) and lung resistance protein: functional activity of P-gp
      and MRP present in the doxorubicin-resistant human K562 cell lines.
AB  - Previous studies have reported that P-glycoprotein (P-gp), a transmembrane efflux
      pump involved in multidrug resistance (MDR), was overexpressed in the doxorubicin
      (Dox)-resistant human erythroleukemia cell line K562. Nevertheless, several
      results suggested that P-gp was not the only mechanism involved in these
      resistant cells. Sequential co-expression of other MDR-associated proteins was
      sometimes reported, as MDR-associated protein (MRP) and lung resistance protein
      (LRP), in different MDR cell lines. Thus, mRNA expression and stability of P-gp,
      MRP and LRP were analyzed, while their corresponding protein levels were
      quantified in correlation with functional assay, in the K562 cell line and two
      Dox-resistant variants (K562/R). Their P-gp content was in accordance with their
      degree of resistance, but not as much in the level of mRNA expression, suggesting
      a post-transcriptional regulation. On the other hand, MRP could play a minor role
      in MDR because of an unchanged expression in K562/R sublines. A surprising
      progressive disappearance of LRP in both resistant cells suggested that the
      original mechanism of drug redistribution may be operative, involving a negative
      role for LRP.

PMID- 11290873
TI  - Evaluation of GL331 in combination with paclitaxel: GL331's interference with
      paclitaxel-induced cell cycle perturbation and apoptosis.
AB  - Combination of selecting agents that act on different cellular mechanisms is a
      common strategy in cancer chemotherapy. GL331 is a new potent topoisomerase II
      (Topo II) poison; distinctly, paclitaxel is a microtubule-interfering cancer
      chemotherapeutic agent. In this study, we intended to evaluate the efficacy of
      combining GL331 with paclitaxel in cell killing and apoptotic induction in
      nasopharyngeal carcinoma NPC-TW01 cells. By MTT and internucleosomal DNA cleavage
      assays, we found that pretreatment or simultaneous treatment of NPC-TW01 cells
      with GL331 could significantly interfere with paclitaxel's cell killing and
      apoptosis-inducing activity. When the administration schedule was reversed, the
      cytotoxicity of GL331 was attenuated by paclitaxel pretreatment. The anti-cancer
      activity produced by combining GL331 with paclitaxel was obviously lower than the
      addition of the activities of two individual agents. NPC-TW01 cells were treated
      with GL331 and 3H-labeled paclitaxel simultaneously or with GL331 before 3H
      labeled paclitaxel. In both conditions, GL331 did not reduce the [3H]paclitaxel
      level in the cells, suggesting that GL331's interference with paclitaxel's cell
      killing and apoptosis-inducing efficacy did not result from any inhibition of
      cellular uptake or retention of paclitaxel. In addition, we found that GL331
      induced perturbation of cell cycle progression dramatically over-rode the
      patterns of mitotic arrest induced by paclitaxel, and the mechanism could be the
      inhibition of cyclin B1/CDC2 kinase and MAD2 checkprotein activities.

PMID- 11290874
TI  - Effect of hydroxyzine on the transport of etoposide in rat small intestine.
AB  - Etoposide, an anti-neoplastic agent and a substrate of P-glycoprotein (P-gp),
      exhibits variable oral bioavailability. P-gp, the multidrug resistance gene
      (mdr1) product, has been considered as an absorption barrier against intestinal
      drug absorption. Terfenadine, an antihistamine, has been shown to be a P-gp
      inhibitor. The current study was designed to assess the effect of hydroxyzine, an
      antihistamine, on the transport of etoposide in the small intestine. Everted rat
      gut sacs were used to determine the absorption and exsorption of etoposide under
      different conditions, as rhodamine 123 was chosen to evaluate the role of P-gp in
      the drug interaction. The results showed that the transport of etoposide was
      significantly increased from the luminal site to the serosal site in the jejunum
      by 2- and 4-fold after 90 min in the presence of hydroxyzine and quinidine,
      respectively. A similar trend was observed in the ileal sacs. This in vitro
      exsorption study also demonstrated that hydroxyzine could reduce the efflux of
      etoposide to the luminal site in either jejunum or ileum. The effect of
      hydroxyzine on the pharmacokinetics of etoposide differed by the in vivo route of
      administration, thus assuming clinical importance for chemotherapeutic treatment.

PMID- 11290875
TI  - Incoherence of neuroimaging studies of attention deficit/hyperactivity disorder.
AB  - Neuroimaging studies have been conducted with increasing frequency in recent
      years in attempts to identify structural and functional abnormalities in the
      brains of persons with attention deficit/hyperactivity disorder. Although the
      results of these studies are frequently cited in support of a biologic etiology
      for this disorder, inconsistencies among studies raise questions about the
      reliability of the findings. The present review shows that no specific
      abnormality in brain structure or function has been convincingly demonstrated by
      neuroimaging studies. Implications regarding stimulant treatment for attention
      deficit/hyperactivity disorder are discussed.

PMID- 11290876
TI  - Intravenous administration of magnesium sulfate in acute stroke: a randomized
      double-blind study.
AB  - A randomized, placebo-controlled, double-blind study was performed as a pilot
      study to examine the benefit of the administration of magnesium sulfate given
      intravenously as a protective substance during the first 24 hours following a
      stroke. Patients who had cortical infarction in the middle cerebral artery
      territory with moderate to severe neurologic deficits lasting for more than 15
      minutes with onset less than 24 hours were included. The patients were treated
      with magnesium sulfate or placebo for 5 days and examined by a blinded
      investigator. Patients had follow-up for 30 days. The primary efficacy variable
      was the proportion of patients reaching mild to moderate neurologic deficit on
      the Orgogozo scale (80 points) and relative functional independence on the
      Barthel index (60 points). Orgogozo scale and Mathew scale values were obtained
      on admission and days 2, 4, 8, and 30 after stroke. Barthel activities of daily
      living index and Rankin disability score were obtained on day 30. Forty-one
      patients (22 given treatment and 19 given placebo) demonstrated significant
      beneficial effects on the Orgogozo scale (84 +/- 11 vs. 64 +/- 10, p < 0.0001)
      and (83 +/- 14 vs. 70 +/- 15, p < 0.009), respectively. At the end of 1-month
      follow-up, the Barthel ADL index was nonsignificantly higher and the Rankin
      disability score was marginally significantly lower in the magnesium-treated
      group (84 +/- 26 vs. 71.8 +/- 26, p < 0.143) than in control subjects (2.3 +/-
      1.1 vs. 3 +/- 1.3, p < 0.077). Intravenous magnesium sulfate had significant
      positive effect on the outcome in patients with acute stroke. Further studies on
      a larger scale are needed to confirm these findings.

PMID- 11290877
TI  - Dose-response study of the analgesic effect of lanepitant in patients with
      painful diabetic neuropathy.
AB  - Lanepitant is effective in the formalin analgesic model suggesting efficacy in
      painful neuropathy. This study was designed to evaluate the dose-response effect
      of lanepitant in patients with daily moderate to severe, bilateral, distal
      neuropathic pain. After a 1-to 3-week lead-in period, patients were randomly
      allocated to double-blind, parallel treatment with lanepitant 50 mg daily (n =
      27), 100 mg daily (n = 27), 200 mg twice daily (n = 13), or placebo (n = 26) over
      8 weeks. Patients reported average daytime pain and average nighttime pain
      intensity. Plasma concentrations and amount of adjunctive analgesic medication
      were obtained at all visits after baseline. Patient global evaluation and
      clinician global impression were obtained at weeks 3 and 8. Safety was assessed
      by adverse events, vital signs, laboratory analytes, and electrocardiogram. No
      dosage of lanepitant differed significantly from placebo. Efficacy did not
      increase with lanepitant dosage, and higher plasma concentrations were no more
      effective than lower plasma concentrations. The adverse event diarrhea was more
      frequent for lanepitant-treated patients. Although well tolerated, lanepitant was
      ineffective in relieving pain of diabetic neuropathy.

PMID- 11290878
TI  - Changes in color vision after a single dose of vigabatrin or carbamazepine in
      healthy volunteers.
AB  - In patients with epilepsy the older antiepileptic drugs induce distinct
      electroencephalographic changes and may also alter visual function. Although the
      effects of the newer antiepileptic drugs on the electroencephalogram remain less
      clear, long-term treatment with vigabatrin (VGB) has been reported to induce
      severe and permanent visual impairment. Our aim in this study was to investigate
      the effects of a single oral dose of VGB and carbamazepine (CBZ) on visual
      function in normal healthy volunteers randomly assigned to three groups according
      to a single-blind, placebo-controlled design. All subjects underwent color visual
      evoked potential tests and color perimetry at baseline and after receiving
      placebo, VGB (2,000 mg) or CBZ (400 mg). Whereas CBZ induced a mild overall
      impairment of the chromatic and achromatic systems, VGB induced a selective blue
      impairment. The differential changes the two antiepileptic drugs induced in
      visual tests presumably depend on their different mechanisms of action. The
      selective blue impairment in color visual tests in VGB-treated healthy subjects
      is consistent with gamma-aminobutyric acid (GABA)-ergic inhibition also at
      retinal level. Hence, color visual tests may be suitable to detect initial visual
      abnormalities in VGB-treated patients with epilepsy.

PMID- 11290879
TI  - Catechol-O-methyltransferase decreases levodopa toxicity in vitro.
AB  - The purpose of this study was to examine the effects of 3-O-methylation by
      catechol-O-methyltransferase (COMT) on the toxicity of levodopa in neuronal
      cultures. High concentrations of levodopa are toxic in vitro. Therefore, there is
      concern that long-term treatment with levodopa in patients with Parkinson's
      disease might accelerate the rate of degeneration of nigrostriatal neurons.
      However, recent studies have suggested that, while levodopa is harmful in vitro,
      it may not be toxic in vivo. A possible defense mechanism is by means of
      metabolic shunting of levodopa excess to 3-O-methyldopa by COMT in peripheral and
      central nervous system tissues. In this study we examine whether the use of COMT
      inhibitor, which reduced the levels of 3-O-methyldopa, affect levodopa toxicity.
      Mice cerebellar granule neurons, PC12, and neuroblastoma cells were used, and
      their viability following exposure to levodopa and COMT with and without
      tolcapone, a COMT inhibitor, was measured by neutral red staining. Auto-oxidation
      of levodopa was evaluated using a spectrophotometer (690 nm). We found that 3-O
      methyldopa, unlike levodopa, was not toxic to all cells examined. Addition of
      purified COMT to levodopa prevented its auto-oxidation and markedly attenuated
      its cytotoxicity in vitro. Additional tolcapone reversed the protective effect of
      COMT. The agent 3-O-methyldopa is not toxic to cell cultures. Catechol-O
      methyltransferase attenuates toxicity of levodopa in vitro by its metabolism to
      nontoxic 3-O-methyldopa.

PMID- 11290880
TI  - Donepezil, rivastigmine, and vitamin E in Alzheimer disease: a combined P300
      event-related potentials/neuropsychologic evaluation over 6 months.
AB  - The latency of P300 "cognitive" event-related potentials changes if cholinergic
      activities of the central nervous system are pharmacologically manipulated. We
      tested the hypothesis that the new cholinesterase inhibitors donepezil (DPZ) and
      rivastigmine (Riv) may have an effect on the frequently abnormal P300 component
      in patients with Alzheimer disease (AD), thereby allowing a significant
      evaluation of cholinesterase inhibitors. We evaluated 60 patients with mild to
      moderately severe probable AD, in comparison with 60 age-matched control
      subjects, with P300 recordings and neuropsychologic examinations. Forty patients
      were randomly assigned in a double-blinded trial to 5-10 mg/d DPZ versus 2,000
      IU/d vitamin E, and 20 patients were instead treated in an open trial with 1.5 to
      12 mg/d Riv. In patients treated with vitamin E, we observed latency increments
      (7.4 +/- 3.5 msec) correlated with worsening neuropsychologic test scores. In
      patients treated with DPZ and Riv, we found significant P300 latency reductions
      (15.3 +/- 3.2 msec and 22.0 +/- 3.3 msec). Shorter P300 latencies were associated
      with higher Wechsler Adult Intelligence Scale scores and with lower AD Assessment
      Scale-cognitive subscale (ADAS-cog) scores (R = 0.72). Correlations between ADAS
      cog changes and P300 changes significantly separated patients treated with DPZ
      and Riv from those treated with vitamin E. Administration of DPZ and Riv reduced
      the latencies of P300 components proportionately to neuropsychologic test
      improvements. Combined P300 and neuropsychologic test evaluation significantly
      separated DPZ-treated patients and Riv-treated patients from vitamin E-treated
      patients.

PMID- 11290881
TI  - A revised excitotoxic hypothesis of schizophrenia: therapeutic implications.
AB  - A revision of an "excitotoxic hypothesis" of schizophrenia is summarized. The
      hypothesis suggests that in, at least, a subtype of patients with schizophrenia,
      progressive excitotoxic neuronal cell death in hippocampal and cortical areas
      occurs via "disinhibition" of glutamatergic projections to these areas. Patients
      who have excitotoxic damage would be expected to have poor outcomes
      characterized, perhaps, by anatomic evidence of progressive neurodegeneration,
      pronounced negative symptoms and cognitive deficits, and profound psychosocial
      deterioration. Disinhibited glutamatergic activity could result from inhibition
      of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission and a
      consequent failure to stimulate inhibitory gamma-aminobutyric acid (GABA)-ergic
      interneurons, and/or anatomic degeneration of inhibitory GABAergic interneurons.
      The result of these hypothesized mechanisms is excessive stimulation of the alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate class of
      glutamate receptor complexes. In turn, this excessive stimulation of AMPA/kainate
      receptors could lead to disruption of ionic gradients, depletion of energy
      reserves expended in an attempt to restore and maintain the ionic disequilibrium
      across neuronal membranes, generation of reactive oxygen species, and cell death
      from apoptotic and other mechanisms. The postulated existence of disinhibited
      glutamatergic neurotransmission and the subsequent cascade of excitotoxic events
      resulting from NMDA receptor hypofunction (NRH), anatomic degeneration of
      inhibitory GABAergic interneurons, or a combination of the two has suggested a
      diverse variety of experimental therapeutic interventions for schizophrenia.
      These interventions include facilitation of NMDA receptor-mediated
      neurotransmission, potentiation of GABAergic neurotransmission, antagonism of
      AMPA/kainate receptors, and "quenching" of locally generated reactive oxygen
      species. In fact, several of these approaches have already been pursued or are
      proposed as part of a systematic clinical investigation of the revised
      excitotoxic hypothesis of schizophrenia.

PMID- 11290882
TI  - The effect of catechol-O-methyltransferase inhibition with entacapone on
      cardiovascular autonomic responses in L-Dopa-treated patients with Parkinson's
      disease.
AB  - We have compared the effects of entacapone, a peripherally acting catechol-O
      methyltransferase (COMT) inhibitor, and placebo on cardiovascular autonomic
      responses in L-Dopa/dopa decarboxylase inhibitor-treated patients with
      Parkinson's disease (PD). In a double-blind, randomized, crossover study with two
      consecutive 1-week treatment periods, a battery of cardiovascular reflex tests
      (orthostatic, Valsalva, deep breathing, and isometric hand grip tests) was
      performed in a group of 15 patients with idiopathic PD. The first set of tests
      was performed after withholding L-Dopa overnight (control, "off" stage). The
      second and third sets of tests were performed in "on" stage after 1-week
      treatment with either entacapone 200 mg or placebo administered with each dose of
      L-Dopa/dopa decarboxylase (DDC) inhibitor. Valsalva, deep breathing, and
      orthostatic tests demonstrated no statistically significant differences in the
      ratio of the longest and shortest electrocardiographic R-to-R wave (R-R)
      intervals between entacapone and placebo or between study treatments and control.
      Blood pressure responses to both orthostatic challenge and prolonged isometric
      work (hand grip test) were similar between treatments. Systolic orthostatic
      hypotension was observed in only one patient during the control test, but it
      occurred more frequently after L-Dopa/DDC inhibitor, regardless of concomitant
      administration of either entacapone (n = 3) or placebo (n = 4). Peripheral COMT
      inhibition with entacapone does not significantly alter cardiovascular autonomic
      responses in L-Dopa-treated patients with PD.

PMID- 11290883
TI  - Estrogen supplementation in the posthypoxic myoclonus rat model.
AB  - The objective of the study was to investigate the effects of estrogen on severity
      and duration of myoclonus in the rat cardiac arrest model of posthypoxic
      myoclonus. Female sex hormones affect a variety of movement disorders and alter
      dopaminergic and serotonergic pharmacology. Although women represented three
      fourths of patients from the original report of Lance and Adams and 80% of the
      largest published series, the impact of estrogens on myoclonus has never been
      studied. Twelve previously ovariectomized female rats underwent 8 minutes of
      mechanically induced cardiac arrest and were resuscitated according to a
      standardized protocol. On the same day, they were randomly assigned to
      subcutaneous treatment with a 21-day, 0.5-mg, 17 beta-estradiol or matching
      placebo pellet. Animals were tested daily with 7 sets of 45 auditory stimuli for
      10 days, and myoclonus scores were obtained using a 5-point interval scale.
      Comparisons were based on two-sample Wilcoxon rank-sum tests. Estrogen treatment
      significantly enhanced myoclonus intensity and duration: mean peak myoclonus
      score, 210.2 +/- 18.0 versus 180 +/- 28.5 (p = 0.031); mean number of days above
      baseline, 9.2 +/- 0.4 versus 5.7 +/- 2.3 (p = 0.004); mean score on day 10, 90.7
      +/- 38.7 versus 27.0 +/- 20.6 (p = 0.016). All estrogen-treated animals were
      above baseline on day 10 compared with none in the placebo group. Estrogen
      enhances and prolongs posthypoxic myoclonus, suggesting that female gender and
      estrogen status may play a pivotal role as a risk factor for human posthypoxic
      myoclonus.

PMID- 11290884
TI  - The hiccup reflex arc and persistent hiccups with high-dose anabolic steroids: is
      the brainstem the steroid-responsive locus?
AB  - Hiccups have been classified as a neurologic reaction triggered by a multitude of
      factors. There are only a few reports of persistent hiccups associated with oral
      and intravenous corticosteroid use in the medical literature. It has been
      proposed that corticosteroids lower the threshold for synaptic transmission in
      the midbrain and directly stimulate the hiccup reflex arc. There is a recent
      report of progesterone-induced hiccups, which were thought to occur secondary to
      the glucocorticoid-like effects of progesterone on the brainstem. We report the
      first case of anabolic steroid-induced hiccups occurring in an elite power
      lifter. The hiccups occurred within 12 hours of the individual increasing his
      doses of oral anabolic steroids and persisted for 12 consecutive hours until
      medical attention was sought. In this report the pathophysiology of anabolic
      steroid-induced hiccups is discussed, and the postulated relationships of
      steroids and the hiccup reflex arc reviewed.

PMID- 11290885
TI  - Heroin-induced rhabdomyolysis as a cause of reflex sympathetic dystrophy.
AB  - Reflex sympathetic dystrophy is an excessive or abnormal response of the
      sympathetic nervous system in an extremity to an injury or other condition. The
      authors describe a 37-year-old man who experienced constant pain and vasomotor
      instability in both feet after nontraumatic rhabdomyolysis secondary to smoking
      heroin. Three-phase bone scintigraphy was performed and revealed significantly
      increased blood-flow, blood-pool, and delayed-phase radioactivity. The follow-up
      three-phase bone scinitigram showed less radiotracer uptake that was consistent
      with a good response to calcitonin therapy. Heroin-induced rhabdomyolysis should
      be added to the list of precipitating conditions that can induce this syndrome.

PMID- 11290886
TI  - Lymphoscintigraphic sentinel node imaging and gamma probe detection in breast
      cancer with Tc-99m nanocolloidal albumin: results of an optimized protocol.
AB  - PURPOSE: The purpose of this study was to aid in the standardization of
      lymphoscintigraphy for detecting the sentinel node (SN) in breast cancer using Tc
      99m-labeled nanocolloidal albumin. MATERIALS AND METHODS: One hundred twenty
      three women with proved breast cancer were enrolled. Four injections of 10 to 15
      MBq (0.27 to 0.41 mCi) Tc-99m nanocolloid in 0.1 ml physiologic saline were
      administered intra- and subdermally at the margin of the skin overlying the
      tumor. Planar scintigraphic images in the lateral and anterior projections were
      obtained 2.5 to 18 hours after tracer administration. With a gamma probe used as
      a guide, all radioactive lymph nodes in the axilla were resected. Complete
      dissection then followed. RESULTS: In 116 of the 123 (94%) women, axillary nodal
      tracer uptake was revealed. Six of the 7 women in whom detection failure occurred
      had histologically proved tumor infiltration of the lymphatics and axillary
      involvement. In 36 (31%) of the patients with visualized lymph nodes, the SN was
      metastatic. The remaining 80 patients with negative SN included three cases with
      axillary involvement. The sensitivity of the SN with respect to the histologic
      status of the entire axilla thus was 92.3%, and the negative predictive value was
      96.3%. The overall accuracy of the method was 97.4%. The number of hot nodes in
      women with and without axillary involvement was significantly different.
      CONCLUSIONS: The described protocol represents an easily reproduced and reliable
      method for SN detection in breast cancer. Furthermore, the number of visualized
      axillary nodes reflects the histologic status of the axilla.

PMID- 11290887
TI  - F-18 FDG positron emission tomography in primary breast non-Hodgkin's lymphoma.
AB  - A 50-year-old woman had an irregular, mobile, firm right breast mass that became
      progressively larger in the past 3 months that measured 18 x 15 cm at the time of
      examination. She had no nipple discharge or skin changes. A 2-[18F]-fluoro-2
      deoxy-D-glucose positron emission tomography (FDG PET) showed a ring-shaped
      breast uptake consisting of high peripheral glycolytic activity and a cold center
      most likely representing necrosis or hemorrhage despite the absence of a history
      of trauma, surgical intervention, chemotherapy, or radiation to the breast. Whole
      body images did not show any evidence of lymph node involvement or distant
      metastases. These results were confirmed by computed tomography of the chest,
      abdomen, and pelvis. Cytologic examination of a fine-needle aspiration of the
      breast mass showed diffuse large B-cell, intermediate grade, non-Hodgkin's
      lymphoma. Although it occurs infrequently, primary breast lymphoma should be
      considered in patients with a breast mass that shows a ring-shaped FDG uptake. A
      PET scan, in contrast to other imagining techniques, offers the advantage of
      screening the entire body, excluding the presence of metastases, and confirming
      the primary origin of the breast lymphoma.

PMID- 11290888
TI  - Iodine-131 ablation therapy for a patient receiving peritoneal dialysis.
AB  - The authors describe a patient with follicular thyroid carcinoma who was
      receiving continuous ambulatory peritoneal dialysis to manage end-stage renal
      disease. To deliver radioiodine therapy to ablate thyroid remnants safely and
      under optimal conditions, the behavior of 37 MBq (1 mCi) I-131 was followed daily
      for 3 days. Blood activity and total body count decreased with a half-life of 100
      hours (4.17 days). The daily iodide removal rate, estimated as a percentage of
      the total administrated activity, was low: 5.3% to 8.6% in peritoneal dialysate
      and 1.3% to 2.2% in urine. The thyroid uptake, measured using a probe, was 2.4%
      to 2.1% from day 1 to day 3 and 1.9% later at day 8. The volume of thyroid
      remnants was determined by ultrasonography to be 0.6 g. The patient received a
      reduced ablative I-131 dose of 814 MBq (22 mCi). Radiation emitted from the
      patient after I-131 therapy, monitored using a radiation monitor probe located at
      a distance of 1 meter, decreased with an effective half-life of 70 hours (2.9
      days). The integration of the curve from t = 0 showed a level always less than 25
      microSv/hour as early as 24 hours after treatment. Because the iodine removal
      rate is continuous but low in a case of peritoneal dialysis, smaller therapeutic
      doses must be administered to deliver maximal radiation to residual thyroid
      tissue while minimizing excessive radiation exposure to patients, their families,
      and medical staff.

PMID- 11290889
TI  - Ectopic goiter masquerading as submandibular gland swelling: a case report and
      review of the literature.
AB  - Ectopic thyroid glands generally occur in the midline as a result of abnormal
      median migration, and their presence lateral to the midline is rare. A 12-year
      old boy had a swelling in the left submandibular region that imaging techniques
      showed to be an ectopic thyroid gland, although no thyroid tissue was seen in the
      normal location. Only eight cases of lateral aberrant thyroid tissue have been
      reported. The importance of being aware of the possibility of ectopic thyroid
      tissue as a submandibular region swelling has an important bearing on disease
      management. A pertinent review of the literature and its management is included.

PMID- 11290890
TI  - Neonatal hypothyroid disease: absent salivary gland evident on technetium-99m
      pertechnetate scan.
AB  - PURPOSE: Technetium-99m pertechnetate scintigraphy is a well-established
      technique for diagnosing congenital hypothyroid disease. However, the
      biodistribution of pertechnetate (TcO4-) in neonates and young infants is not
      well documented. The purpose of this study was to analyze and document the
      biodistribution of TcO4- in young infants. MATERIALS AND METHODS: Scintigraphic
      studies of 31 patients being examined for hypothyroid disease were analyzed. All
      patients had elevated levels of thyroid-stimulating hormone. Dyshormonogenesis
      was diagnosed in 7 patients, ectopic thyroid glands in 19, and agenesis in 5.
      RESULTS: Images of the neck, chest, and abdomen taken in the anterior and left
      lateral positions using a low-energy, all-purpose collimator were reviewed.
      Twenty-six of the patients had no accumulation of the isotope in the salivary
      glands and 11 had no gastric uptake on either view. CONCLUSIONS: Based on the
      absence of salivary gland activity in the patients examined, this study suggests
      that this is a normal finding in infants younger than 3 months. A lateral view of
      the neck with markers is sufficient to localize the thyroid gland, because any
      activity in the neck region would belong to the thyroid. Furthermore, poor and
      variable uptake of the isotope in the stomach may lead to false-negative results,
      so caution is urged in the use of this tracer in Meckel's scintigraphy in young
      infants, particularly if the study findings are within normal limits.

PMID- 11290891
TI  - F-18 FDG uptake in the large arteries: a new observation.
AB  - PURPOSE: The cellular components of the atherosclerotic plaque, such as
      macrophages, exhibits high glucose metabolic activity. The aim of this study was
      to show the frequency of vascular uptake and possibly to explain the significance
      of this finding on fluorodeoxyglucose (FDG) positron emission tomographic (PET)
      scans. METHODS: We evaluated the presence of FDG vascular uptake in 132
      consecutive patients undergoing whole-body PET scans and 5 patients who had only
      lower extremity scans. The presence of vascular FDG uptake was assessed in the
      abdominal aorta, iliac, and proximal femoral arteries on the 132 whole-body
      scans, whereas only the femoral and the popliteal arteries were examined on the
      leg scans. The patients' ages ranged from 20 to 80 years, and they were divided
      into three age groups: 35 patients were younger than 40 years (group 1; mean age,
      32.4 years), 48 patients were 41 to 60 years (group 2; mean age, 50.3 years), and
      54 patients were older than 60 years (group 3; mean age, 70.3 years). RESULTS:
      Fifty percent (69 of 137) of the total population showed vascular FDG uptake in
      at least one vessel. Thirty-four percent (12 of 35) of group 1, 50% (24 of 48) of
      group 2, and 61% (33 of 54) of group 3 showed vascular wall uptake (P = 0.017
      between groups 1 and 3). In addition, the correlation between the mean age of the
      age groups and the prevalence of FDG vascular uptake is strong (r = 0.99).
      CONCLUSIONS: Vascular FDG uptake is present in 50% of the patients examined for
      this study, with an increased prevalence in older patients. This vascular uptake
      might be explained by smooth muscle metabolism in the media, subendothelial
      smooth muscle proliferation from senescence, and the presence of macrophages
      within the atherosclerotic plaque. The relative contribution of these sources
      needs further investigation.

PMID- 11290892
TI  - Radionuclide lung imaging in respiratory decompression sickness: potential role
      in the diagnosis and evaluation of hyperbaric therapy.
AB  - Of the more than 3.5 million trained divers in the United States, many will
      experience various illnesses specific to divers. Most of these illnesses are
      related to the changes in absolute pressure that divers experience while diving.
      During and after ascent, a diver is at risk for decompression sickness and
      pulmonary barotrauma. A very rare casualty is pulmonary decompression sickness
      from immersion. This is a literature review and case report of a young woman with
      acute respiratory decompression sickness who had defects on perfusion lung
      imaging after a diving accident and after hyperbaric oxygen therapy. However, the
      perfusion defects reverted to normal in less than 24 hours. Possible explanations
      for the changes in the appearances of the scans are offered and discussed. This
      case report shows the potential utility of lung scanning in the diagnostic
      examination of these patients and the evaluation of the adequacy of treatment
      with hyperbaric oxygen therapy. A greater use of ventilation-perfusion lung scans
      in the treatment of such patients may establish its role more definitely.

PMID- 11290894
TI  - Hepatobiliary scintigraphic findings in obstructed intrahepatic choledochal cyst
      before and after surgery.
AB  - The authors describe a 10-week-old boy who presented with symptoms of progressive
      obstructive jaundice and abdominal distension. Clinical examination revealed
      gross hepatomegaly. A preoperative Tc-99m mebrofenin hepatobiliary study showed a
      large photopenic area involving the entire right lobe of the liver that did not
      communicate with the biliary system. Ultrasonography revealed a huge cystic mass
      with a few intracystic septae involving nearly the entire liver parenchyma. Under
      ultrasound guidance, a pigtail catheter was inserted into the cyst and produced
      free drainage of bile-stained fluid. Subsequently, an obstructed choledochal cyst
      was diagnosed clinically, and a right hepatectomy followed by a Roux-en-Y loop
      implantation on the raw surface of the left lobe were performed. Serial
      postoperative Tc-99m mebrofenin hepatobiliary studies showed marked improvement
      in liver function and biliary drainage with significant regeneration of the liver
      parenchyma.

PMID- 11290893
TI  - Detection of minimal residual disease in acute leukemia by Tc-99m MIBI femoral
      marrow imaging.
AB  - To determine the potential of Tc-99m MIBI femoral marrow imaging for detecting
      minimal residual disease in acute leukemia, MIBI images of 68 patients with acute
      leukemia and 110 control patients were examined. MIBI accumulation was classified
      into three patterns: not detectable, mild accumulation, and clearly visualized
      accumulation. Clearly visualized accumulation was interpreted as abnormal. The
      mean uptake ratio of the femoral marrow to muscle was calculated. Forty-five
      patients who were in complete remission (CR) at the time of MIBI imaging had a
      follow-up study (mean interval, 23 months). Clearly visualized accumulation was
      demonstrated in 35 patients with acute leukemia: in 7 patients before starting
      induction chemotherapy, in 12 patients after relapse, and in 16 of the 49
      patients in the CR group. Mild accumulation was demonstrated in 14 patients in
      the CR group and in 13 control group patients. No detectable accumulation was
      observed in 19 patients in the CR group and in 97 control patients. The marrow
      and muscle uptake ratio of patients before starting chemotherapy (2.29 +/- 0.26)
      was greater compared with that in patients after relapse (1.78 +/- 0.44, P <
      0.02) and in patients with abnormal accumulation despite complete remission (1.84
      +/- 0.36, P < 0.01). The uptake ratio in patients with abnormal accumulation
      despite CR was higher compared with patients with mild accumulation in CR (1.26
      +/- 0.13, P < 0.001) and controls (1.23 +/- 0.10, P < 0.001) who had mild
      accumulation. Fifteen patients with abnormal accumulation despite CR had a
      markedly greater relapse rate (66.7% > 10.0%, P < 0.005), a higher mortality rate
      (46.7% > 6.7%, P < 0.01), and shorter remission time (8.7 +/- 10.2 months < 35.9
      +/- 20.1 months, P < 0.001) compared with 30 patients without abnormal
      accumulation in CR. MIBI femoral marrow imaging may be a useful and simple method
      for monitoring levels of residual leukemic cells. Clearly visualized MIBI
      accumulation may be a marker for relapse.

PMID- 11290895
TI  - Clinical advantages of interictal SPECT coregistered to magnetic resonance
      imaging in patients with epilepsy.
AB  - PURPOSE: The aim of this study was to investigate the clinical value of
      coregistration of interictal SPECT and magnetic resonance imaging (MRI) in
      patients with partial epilepsy. MATERIALS AND METHODS: Seventeen patients with
      partial epilepsy were examined with I-123 IMP or Tc-99m ethyl cysteinate dimer
      SPECT during the interictal phase. The SPECT images were automatically
      coregistered to axial T1 weighted MRIs. Asymmetry indexes (AIs) were calculated
      in both nonregistered images and coregistered images. RESULTS: SPECT images
      showed areas of decreased tracer uptake in 12 patients. In two patients, the
      relation between the tumor and the extent of decreased uptake became more
      accurate in the coregistered images. In five cases, the coregistered images
      clearly showed that the decreased uptake was located in the sulcus. The AIs were
      significantly reduced from 14.29 +/- 7.23 to 5.86 +/- 3.48 (P < 0.001) after the
      images were coregistered in these cases. In five cases, the coregistered images
      indicated that the decreased areas were in agreement with the cortical findings.
      No significant differences in the AIs were observed in these cases (16.50 +/-
      6.19 versus 17.83 +/- 4.45). Thus, the coregistered images were useful not only
      to differentiate actual hypoperfusion from artificial hypoperfusion resulting
      from partial volume effects but also to improve the accuracy of AIs. CONCLUSION:
      The coregistration of interictal perfusion SPECT and MRI is useful not only to
      provide precise functional and anatomic mapping but also to improve the accuracy
      of calculations of the semiquantitative analysis of regional cerebral blood flow
      parameters during the interictal state of epilepsy.

PMID- 11290896
TI  - Ga-67 scintigraphy in pericarditis associated with rheumatoid arthritis.

PMID- 11290897
TI  - Delineation of unexpected muscle trauma.

PMID- 11290898
TI  - Primary echinococcal cyst: a rare cause of cold thyroid nodule on thyroid scan.

PMID- 11290899
TI  - Differential effects of bisphosphonate on Paget's disease and metastatic
      prostatic carcinoma-bone scan findings.

PMID- 11290900
TI  - Pseudohepatic cavernous hemangioma resulting from a prominent left portal vein of
      a portal systemic shunt collateral on Tc-99m SPECT red blood cell scintigraphy.

PMID- 11290901
TI  - Visualization of the genitalia in renal transplant evaluation.

PMID- 11290902
TI  - Horseshoe kidney on FDG positron emission tomographic imaging is easily confused
      with malignancy.

PMID- 11290903
TI  - Isolated carpal bone metastases from bronchogenic cancer evident on bone
      scintigraphy.

PMID- 11290904
TI  - Accumulation of Tc-99m HMDP in extramedullary plasmacytoma of the stomach.

PMID- 11290905
TI  - Labeled leukocyte accumulation corresponding to an intestinal polyp in
      inflammatory bowel disease.

PMID- 11290906
TI  - Tumor-like accumulation on Tl-201 SPECT in subacute hemorrhagic cerebral
      infarction.

PMID- 11290907
TI  - Scintigraphic detection of bronchobiliary fistula in a patient with bile in
      bronchial secretions.

PMID- 11290908
TI  - Hepatobiliary scintigraphy to detect duodenogastric reflux: intravenous
      administration of Tc-99m pertechnetate to define the location of the stomach.

PMID- 11290909
TI  - A hypervascular ossifying fibroma of the tibia on Tc-99m MDP three-phase bone
      scintigraphy.

PMID- 11290910
TI  - Bone metastasis from primary splenic angiosarcoma to the sacrum demonstrated by
      Tc-99m-labeled red blood cell and Tc-99m MDP bone scintigraphy.

PMID- 11290912
TI  - Inguinal hernia detected during bone scintigraphy.

PMID- 11290911
TI  - Increased uptake at sites of bone marrow biopsy mimicking bony metastases on Tc
      99m MDP bone scintigraphy.

PMID- 11290913
TI  - A central scar in hepatic focal nodular hyperplasia detected on liver SPECT
      imaging.

PMID- 11290914
TI  - Diffuse Tl-201 accumulation in an irradiated area.

PMID- 11290915
TI  - Antiphospholipid Antibodies and Reproductive Problems.

PMID- 11290916
TI  - CONTRACEPTION FOR THE 21st CENTURY.

PMID- 11290917
TI  - Diagnostic Molecular Pathology - Volume X.

PMID- 11290918
TI  - Aging of the human crystalline lens and presbyopia.

PMID- 11290919
TI  - Mechanism of accommodation.

PMID- 11290920
TI  - Accommodation and presbyopia.

PMID- 11290921
TI  - The psyche of presbyopia.

PMID- 11290922
TI  - The correction of presbyopia.

PMID- 11290923
TI  - Bifocal contact lenses in presbyopia.

PMID- 11290925
TI  - Correction of presbyopia with the excimer laser.

PMID- 11290924
TI  - Monovision achieved with excimer laser refractive surgery.

PMID- 11290926
TI  - Clear-lens extraction with multifocal lens implantation.

PMID- 11290927
TI  - The surgical reversal of presbyopia: a new procedure to restore accommodation.

PMID- 11290928
TI  - Anterior ciliary sclerotomy with silicone expansion plug implantation: effect on
      presbyopia and intraocular pressure.

PMID- 11290932
TI  - Postictal EEG suppression and hippocampal atrophy in temporal lobe epilepsy.
AB  - Postictal EEG suppression and slowing recorded with scalp electrodes in patients
      with partial epilepsy is often maximal over the cortical area of ictal onset. The
      aim of this study was to determine whether a quantitative relationship exists
      between immediate postictal EEG suppression and hippocampal atrophy. Immediate
      postictal EEG was analyzed in 31 scalp-recorded seizures obtained from 8 patients
      who underwent temporal lobectomy with seizure-free outcomes (2 left, 6 right).
      Quantitative EEG analysis was performed using a temporal power asymmetry index
      for each frequency band. The hippocampal asymmetry (left-to-right ratio) based on
      T1- and T2-weighted MR images was determined by hippocampal volumetric analysis.
      The relationship between the average temporal power asymmetry index and either T1
      or T2 hippocampal asymmetry ratio was assessed for each frequency band using
      Pearson's correlation coefficient. Only correlations of the temporal power
      asymmetry index with T1 hippocampal asymmetry were significant for the total
      bands (r = 0.768, P < 0.026) and 8-bands (r = 0.728, P < 0.041). The findings
      suggest that a quantitative relationship exists between postictal EEG suppression
      in the 6-frequency band and hippocampal atrophy in temporal lobe epilepsy.

PMID- 11290933
TI  - Marked clozapine-induced slowing of EEG background over frontal, central, and
      parietal scalp areas in schizophrenic patients.
AB  - The authors studied how clozapine treatment of patients with chronic
      schizophrenia affects the scalp topographic distribution of different frequency
      bands on EEG. Twenty-one patients treated with clozapine, in addition to zero to
      two typical neuroleptics (13 patients were treated with clozapine as the only
      neuroleptic), were compared with two control groups: one of healthy subjects and
      another of patients with schizophrenia receiving one to three typical
      neuroleptics and no clozapine. Significant differences in the EEG topography were
      seen between the groups: The theta and delta powers and were increased in the
      clozapine group compared with the two other groups (P < 0.001). Changes were
      observed over all electrodes, and were most prominent at the frontal, central,
      and parietal electrode locations. The nonclozapine-treated group of patients and
      the healthy control group did not differ significantly from each other. These
      results suggest that the topographic EEG features caused by clozapine are quite
      specific to it and can be differentiated from those of other neuroleptics.

PMID- 11290934
TI  - Outpatient seizure identification: results of 502 patients using computer
      assisted ambulatory EEG.
AB  - Patients with epilepsy may not always be able to identify their seizures.
      Epilepsy management relies on patient reporting to validate whether seizures
      occur during treatment. The goal of this study was to assess the frequency of
      unreported seizures recorded during routine outpatient ambulatory EEG recording.
      The authors reviewed 552 records from 502 patients who underwent outpatient 16
      channel computer-assisted ambulatory EEG monitoring (CAA-EEG). Seizure
      identification was evaluated by assessing push-button activation. Partial
      seizures were seen most commonly. A total of 47 of 552 records (8.5%) had partial
      seizures recorded on CAA-EEG, with 29 of 47 (61.7%) with electroclinical seizures
      identified by push-button activation. Seizures on EEG without push-button
      activation were analyzed separately and compared with a self-reported written
      diary to verify lack of recognition. A total of 18 of 47 records (38.3%) had some
      partial seizures that were unrecognized by the patient, and 11 of 47 records
      (23.4%) had seizures recognized only by the computer. The authors conclude that
      patients frequently have seizures outside of the hospital that go unrecognized.
      Underreporting of seizure frequency occurs in the outpatient setting and impacts
      optimal diagnosis and treatment for patients with epilepsy.

PMID- 11290935
TI  - Periodic lateralized epileptiform discharges after evacuation of subdural
      hematomas.
AB  - Periodic lateralized epileptiform discharges (PLEDs) have been recorded in some
      patients with subdural hematomas. In most of the patients, PLEDs occurred before
      the hematoma was evacuated. Five patients (three men and two women) who ranged in
      age from 57 to 88 years had PLEDs and seizures after evacuation of a subdural
      hematoma. The PLEDs occurred 1 to 9 days after evacuation and were associated
      with clinical seizures and altered consciousness. After treatment with
      anticonvulsant agents, the PLEDs and seizures resolved. The presence of PLEDs
      should be considered in patients who, after evacuation of a subdural hematoma,
      have altered consciousness, lateralized neurologic findings, or seizurelike
      activity (or a combination of these features).

PMID- 11290936
TI  - Epileptic seizures and electroencephalographic evolution in genetic
      leukodystrophies.
AB  - The purpose of this study is to explore and compare epileptic seizures and EEG
      evolution in the various types of genetic leukodystrophy (GL). The authors
      reviewed the medical records and analyzed 69 serial EEGs in 27 patients with GLs:
      13 with late infantile metachromatic leukodystrophy, one with juvenile
      metachromatic leukodystrophy, one with globoid cell leukodystrophy, six with X
      linked childhood adrenoleukodystrophy, one with neonatal adrenoleukodystrophy,
      four with classic Pelizaeus-Merzbacher disease (PMD), and 1 with connatal
      Pelizaeus-Merzbacher disease. The diagnoses were made by biochemical and
      molecular studies. Two or more EEG studies with both awake and sleep traces were
      recorded during the varying clinical stages for each patient. At the beginning of
      the GLs, the EEGs were normal or showed mild slowing of background activity.
      Clinical seizures, mainly of focal origin, with progressive slowing and
      paroxysmal discharges on EEGs, usually appeared during the later stages of
      metachromatic leukodystrophy, X-linked childhood adrenoleukodystrophy, and
      classic Pelizaeus-Merzbacher disease. However, intractable seizures, mainly
      generalized in nature, and more severe slowing and abundant paroxysmal discharges
      on EEGs, with commensurate neurologic deterioration, were observed during the
      earlier course of globoid cell leukodystrophy, neonatal adrenoleukodystrophy, and
      connatal Pelizaeus-Merzbacher disease. These results indicate that GLs involve
      not only white matter, but gray matter as well. In all types of GL, there is good
      correlation between the severity of EEG changes, the severity of the diseases,
      and the clinical state of the patient.

PMID- 11290937
TI  - Time-related configuration change in benign focal epileptiform discharges of
      childhood: from a dipole to a negative monopole in a patient with generalized
      epilepsy.
AB  - The case of a 6-year-old child with generalized epilepsy and benign focal
      epileptiform discharges (BFEDs) of childhood is presented. During his first EEG,
      performed when he was 6 years old, the patient had three staring episodes
      accompanied by bursts of 3-Hz spike-and-wave complexes. Interictally, frequent
      BFEDs were seen, configured as dipoles with a right temporal negativity and a
      right frontal positivity. The patient was administered ethosuximide and the
      staring spells disappeared. On follow-up EEG performed 2 years later, no
      generalized discharges were seen. However, the EEG again showed frequent spikes
      with a characteristic morphology of BFEDs. This time they were not configured as
      dipoles, but as monopoles with a maximum negativity over the right frontal
      region. The change in the generator's orientation over time (from a horizontal to
      a vertical dipole) is discussed, as well as the prognostic implications of the
      morphology and configuration of focal spikes. In addition, the authors review the
      coexistence of BFEDs and 3-Hz spike-and-wave complexes in their patient database.

PMID- 11290938
TI  - Effects of modeling errors and EEG measurement montage on source localization
      accuracy.
AB  - The location of an electrical source in the brain can be determined from the EEGs
      the source produces on the scalp by calculating the location of a source in a
      model of the head using the EEGs. Modeling errors produced by differences between
      the actual head and the head model cause localization errors (i.e., errors in the
      calculated location of the source). This is a study of the localization errors
      caused by modeling errors produced by the differences between two features of
      actual head geometry and a spherical head model. The two features are general
      nonspherical head shape and the brain pan (i.e., the very nonspherical lower
      surface of the brain cavity). This is also a study of the localization accuracy
      of different EEG measurement montages when these modeling errors are present. It
      has been found that general nonspherical head shape causes maximum localization
      errors of approximately 1 cm, and that these errors are not very dependent on
      source location or orientation, or EEG montage. The localization errors caused by
      the brain pan are generally larger: The maximum error is approximately 2 cm.
      These errors are very dependent on source location and orientation, and EEG
      montage. The largest errors occur for sources close to and pointing toward the
      brain pan surface. These errors also vary widely with montage: A referential
      montage with the reference point on the bottom of the model has the largest
      errors. Referential montages with reference points on the side or top of the
      model, an average reference montage, or a bipolar montage generally produce much
      smaller errors.

PMID- 11290939
TI  - Phasic and tonic coupling between EEG and EMG demonstrated with independent
      component analysis.
AB  - The authors describe a method for demonstrating the tonic and phasic couplings
      between suitably time-aligned surface eletromyographs (sEMGs) and the
      simultaneously recorded EEGs. The method, based on independent component
      analysis, was applied to data recorded from two normal subjects performing
      sustained submaximal contractions or continual repetitive movements of the arm.
      Augmented datasets, consisting of the EEG and either the sEMG from a single
      muscle (subject 1) or a combination of sEMGs from several muscles (subject 2),
      were analyzed with independent component analysis to determine the EEG/sEMG
      coupling. Each derived coupling consisted of a spatial distribution on the scalp
      and a waveform representing an EEG channel combination coactivating with the
      sEMG. The combinations of sEMGs, derived by applying independent component
      analysis to the simultaneous sEMG recordings from several muscles to create sEMG
      independent components (ICs), were either tonic or phasic with differing periods
      of activation. The topographic distributions on the scalp of the couplings
      between the EEG and sEMG ICs were different for each sEMG IC. The spatial
      distributions of the couplings between tonic sEMG ICs or single-muscle sEMGs and
      the EEG followed topographic patterns in sensorimotor regions. Phasic couplings
      were bifrontal, lateral, and bioccipital. Calculation of coherence between the
      sEMG ICs and calculated EEG combinations agreed well with the frequency spectra
      of the independent component analysis-derived coupling waveforms. These
      preliminary results demonstrate that detection of both the tonic and phasic
      coupling between the sEMG and the EEG is possible when monitoring unpaced
      proximal arm movement. This may thus be a practical means of exploring the
      dynamic cortical/muscle relationships in subjects unable to perform fine finger
      movements, such as patients recovering from stroke.

PMID- 11290940
TI  - Nonlinear dynamic analysis of the EEG in patients with Alzheimer's disease and
      vascular dementia.
AB  - To assess nonlinear EEG activity in patients with Alzheimer's disease (AD) and
      vascular dementia (VaD), the authors estimated the correlation dimension (D2) and
      the first positive Lyapunov exponent (L1) of the EEGs in both patients and age
      matched healthy control subjects. EEGs were recorded in 15 electrodes from 12 AD
      patients, 12 VaD patients, and 14 healthy subjects. The AD patients had
      significantly lower D2 values than the normal control subjects, (P < H > 0.05),
      except at the F7 and the O1 electrodes, and the VaD patients, except at the C3
      and the C4 electrodes. The VaD patients had relatively increased values of D2 and
      L1 compared with the AD patients, and rather higher values of D2 than the normal
      control subjects at the F7, F4, F8, Fp2, O1, and O2 electrodes. The L1 values of
      the EEGs were also lower for the AD patients than for the normal control
      subjects, except in the O1 and the O2 channels, and for the VaD patients at all
      electrodes. The L1 values were higher for the VaD patients than for the normal
      control subjects (F3, F4, F8, O1, and O2). In addition, the authors detected that
      the VaD patients had an uneven distribution of D2 values over the regions than
      the AD patients and the normal control subjects, although the statistics do not
      confirm this. By contrast, AD patients had uniformly lower D2 values in most
      regions, indicating that AD patients have less complex temporal characteristics
      of the EEG in entire regions. These nonlinear analyses of the EEG may be helpful
      in understanding the nonlinear EEG activity in AD and VaD.

PMID- 11290941
TI  - Vagal nerve stimulation does not unkindle seizures.
AB  - The purpose of this study was to investigate a mechanism of action for the effect
      of vagal nerve stimulation on reducing seizures in patients with complex partial
      epilepsy. The hypothesis tested was that vagal nerve stimulation has an
      antikindling effect on epilepsy. The databases of two large clinical trials (E03,
      E05) were accessed, and statistical methods were applied using logarithmic
      transforms and regression analysis. Two parameters--duration of a patient's
      epilepsy before entering the clinical trial and the patient's seizure density
      before entering the clinical trial--were used as markers of subsequent seizure
      control during vagal nerve stimulation. In general, there was not a good fit to
      the regression lines, and the slope of the lines did not conform to the
      hypothesis. The hypothesis that vagal nerve stimulation may unkindle epileptic
      seizures was not supported.

PMID- 11290942
TI  - STATEMENT OF OWNERSHIP MANAGEMENT AND CIRCULATION (Required by 39 U.S.C. 3685).

PMID- 11290961
TI  - The mouse lens fiber-cell intrinsic membrane protein MP19 gene (Lim2) and granule
      membrane protein GMP-17 gene (Nkg7): Isolation and sequence analysis of two
      neighboring genes.
AB  - PURPOSE: The lens fiber cell intrinsic membrane protein MP19 appears to play a
      key role in lens fiber cell structure or communication, and thus
      cataractogenesis. The goal of this study was to isolate and characterize the
      entire gene structure of the MP19 gene, termed Lim2, and to investigate gene
      sequences surrounding this lens-specific gene. METHODS: A 129/SvJ mouse genomic
      DNA library was screened using radioisotope labeled bovine MP19 cDNA. From this
      screening, an 11 kb genomic fragment was isolated which contained the entire Lim2
      gene, and a neighboring gene, Nkg7, which codes for a 17 kDa granulocyte membrane
      protein termed GMP-17. The nucleotide sequence of this entire fragment was
      obtained using double strand automated sequencing techniques. Using CAT and green
      fluorescent protein reporter constructs, Lim2 5'-upstream promoter sequences were
      analyzed. RESULTS: An 11,182 base pair genomic clone containing the entire murine
      Lim2 gene and another downstream gene, Nkg7, was obtained and completely
      sequenced. These two genes are only 1,182 base pairs apart, from the poly(A)
      signal of the Lim2 gene to the published transcriptional start site of Nkg7.
      Interestingly, the protein coded for by Nkg7, GMP-17, is very similar to the
      product of the lens Lim2 gene, MP19, in many respects. Both proteins are
      transmembrane proteins, with each having 4 transmembrane loops. The amino acid
      sequence of the two proteins is 34% identical, and 49% with respect to similar
      amino acids. The size of mouse Lim2 is 5,896 base pairs from the transcriptional
      start site to the poly(A) signal, and contains five exons and four introns. Exons
      2-5 of the Lim2 gene encode a polypeptide of 173 amino acids, having over 92%
      identity to human MP19. Using chloramphenicol acetyltransferase (CAT) and green
      fluorescent protein (GFP) reporter constructs, it was determined that about 160
      bp of sequence upstream from the start of transcription is both necessary and
      sufficient for efficient expression levels as well as tissue specificity of
      expression. CONCLUSIONS: The mouse Lim2 gene is very similar to the human LIM2
      gene, both having the same number of exons and introns. The coding nucleotide
      sequences from both species are 88% identical, and 92% identical at the amino
      acid level. In the immediate 5'-upstream region of these two genes, several
      highly conserved regions are observed. Due to the similarity of the MP19 and GMP
      17 proteins, it is interesting to speculate that the lens MP19 and the lymphocyte
      associated GMP-17 may have originated from one primordial gene which, through
      genetic drift, resulted in two separate proteins having similar functions in two
      widely separated tissue types.

PMID- 11290962
TI  - Postresuscitation management.

PMID- 11290963
TI  - Proceedings of the Guidelines 2000 Conference for Cardiopulmonary Resuscitation
      and Emergency Cardiovascular Care: An International Consensus on Science.

PMID- 11290964
TI  - International Guidelines 2000: the story and the science.

PMID- 11290965
TI  - The chain of survival.

PMID- 11290966
TI  - Action sequence for layperson cardiopulmonary resuscitation.
AB  - Although some minor modifications were forged, the general consensus was to
      maintain most of the current guidelines for phone first/phone fast, no-assisted
      ventilation CPR, the A-B-C (vs C-A-B) sequence of CPR, and the recovery position.
      The decisions to leave these guidelines as they are were based on a lack of
      evidence to justify the proposed changes, coupled with a reluctance to make
      revisions that would require major changes in worldwide educational practices
      without such evidence.Nonetheless, some major changes were made. The time-honored
      procedure ol pulse check by lay rescuers was eliminated altogether and replaced
      with an assessment for other signs of circulation. Likewise, it was recommended
      that even the professional rescuer now check for these other signs of
      circulation. Although professional rescuers may simultaneously check for a pulse,
      they should do so only for a short period of time (within 10 seconds). There was
      also enthusiasm for deleting the ventilation aspect of EMS dispatcher-assisted
      CPR instructions that are provided to rescuers at the scene who are inexperienced
      in CPR. lt was made clear, though, that the data are applicable only to adult
      patients who are receiving CPR and that the data are appropriate most for EMS
      systems with rapid response times.

PMID- 11290967
TI  - Chest compressions and basic life support-defibrillation.

PMID- 11290968
TI  - Rescue breathing and bag-mask ventilation.

PMID- 11290969
TI  - Resuscitation science of pediatrics.

PMID- 11290970
TI  - Cardiopulmonary resuscitation and emergency cardiovascular care. Education.

PMID- 11290971
TI  - Automated external defibrillation/public access defibrillation.

PMID- 11290972
TI  - Use of adjunctive devices in cardiopulmonary resuscitation.

PMID- 11290973
TI  - TOX-ACLS: toxicologic-oriented advanced cardiac life support.

PMID- 11290974
TI  - Treatment of tachyarrhythmias.

PMID- 11290975
TI  - Resuscitation of newborns.

PMID- 11290976
TI  - Airways in pediatric and newborn resuscitation.

PMID- 11290977
TI  - Cardiopulmonary resuscitation and emergency cardiovascular care. Stroke.

PMID- 11290978
TI  - Cardiopulmonary resuscitation and emergency cardiovascular care. Airway devices.

PMID- 11290979
TI  - Use of pressors in the treatment of cardiac arrest.

PMID- 11290980
TI  - Cardiopulmonary resuscitation and emergency cardiovascular care. Acute coronary
      syndromes.

PMID- 11290981
TI  - Ethics in emergency cardiac care.

PMID- 11290982
TI  - Recurrent pneumothorax associated with thoracic endometriosis.
AB  - Herein we report the cause of a 46-year-old woman who presented with recurrent
      right pneumothorax following hysterectomy with right salpingo-oophorectomy for
      pelvic endometriosis. Video-assisted thoracoscopy revealed endometrial implants
      in the posterior parietal pleura and the middle lobe. Ruptured apical blebs were
      also present. The middle lobe lesions and the apical blebs were resected. A
      partial pleurectomy was carried out to remove the endometrial foci in the
      parietal pleura; the remaining pleural surface was mechanically abraded. The
      favorable outcome was confirmed at 2-year follow-up.

PMID- 11290983
TI  - Laparoscopic management of a posterior mediastinal tumor mimicking an adrenal
      neoplasm.
AB  - BACKGROUND: Rarely, a posterior mediastinal mass may mimic an adrenal tumor on
      preoperative computed tomography scan. The intraoperative discovery that a mass
      thought to be associated with the adrenal gland actually is above the diaphragm
      in the posteroinferior mediastinum poses a challenge for the laparoscopic
      surgeon. Conversion to a thoracotomy or to videothoracoscopy incurs additional
      morbidity and risk for the patient. MATERIALS AND METHODS: We describe a
      technique for the transdiaphragmatic removal of a benign mass from the posterior
      mediastinum. A posterior mediastinal tumor was detected during a laparoscopic
      procedure for a suspected right adrenal tumor. Frozen section proved benign, and
      the mass was resected laparoscopically via transdiaphragmatic access to the
      posterior mediastinum. RESULTS: No complications were noted during or after
      surgery. The patient was ready for discharge from the hospital on postoperative
      day 1. CONCLUSIONS: Transdiaphragmatic resection was done successfully instead of
      conversion to a thoracotomy or thoracoscopic procedure for a benign posterior
      mediastinal tumor found incidentally during laparoscopic surgery for a presumed
      adrenal lesion. This transdiaphragmatic approach can be applied to selected
      benign mediastinal masses.

PMID- 11290984
TI  - Laparoscopic resection of an accessory liver and gallbladder.

PMID- 11290985
TI  - Laparoscopic excision of the urachus.
AB  - Embryologically, the urachus represents the obliterated alantois in the form of a
      fibrous cord extending from the dome of the bladder to the umbilicus. Incomplete
      obliteration can result in the formation of an umbilical sinus, fistula, cyst, or
      abscess in the infraumbilical area. The traditional treatment of a residual
      urachus is surgical resection of the entire tract from the dome of the bladder to
      the umbilicus through a lower midline incision. We report the case of a 14-year
      old girl who presented with an abscess below the umbilicus. After initial
      drainage, she developed a sinus that communicated with the navel. Surgical
      resection of the underlying urachus was carried out laparoscopically. The
      peritoneum was incised at the umbilicus, and the whole tract along with the skin
      sinus was excised using diathermy scissors. The lower end was ligated and the
      specimen retrieved. The patient was discharged the following day. One week later,
      her wounds had healed. Histology confirmed an epithelial-lined urachus. We
      believe that laparoscopic excision of a patent urachus is feasible and safe. This
      technique gives the surgeon good access to the area and has a cosmetically better
      result.

PMID- 11290986
TI  - Creating our nursing legacy.

PMID- 11290987
TI  - Change: a matter of survival.

PMID- 11290988
TI  - Outpatient surgery care unit work process redesign.
AB  - Health care practitioners at all levels within an organization have a
      professional responsibility to deliver quality patient care. The overall systems
      operation, as well as customer outcomes, can be enhanced by using redesign and
      process improvement strategies. This article highlights the implementation of
      these change strategies as a part of process improvement efforts in the
      Outpatient Surgery Care Unit (OSCU). OSCU work process redesign was one in a
      series of 8 redesign efforts in the department of Surgical Services. A summary of
      the redesign process and its corresponding educational program is provided. Tools
      used to enhance efficiency and cost savings are also included.

PMID- 11290989
TI  - Use of a modified Postanesthesia Recovery Score in phase II perianesthesia period
      of ambulatory surgery patients.
AB  - Use of discharge criteria in the ambulatory surgery setting has been the topic of
      many research studies and reviews. This article provides a discussion of a
      research utilization project regarding the use of a modified Postanesthesia
      Recovery Score for Ambulatory Patients (PARSAP) in Phase II recovery of a
      perianesthesia unit. The impetus for this project was the closure of a hospital's
      only inpatient ward, resulting in all surgery performed on an outpatient basis.
      Based on community standards and a review of literature, this project evaluated
      the use of the modified PARSAP on ambulatory surgery patients. The intent of the
      project was to improve the flow of patients through the recovery process in an
      effort to contain or reduce costs while still maintaining high-quality patient
      care standards. Results of the project showed a decreased inpatient length of
      stay without any increase in reports of postoperative complications. The
      favorable outcomes of the use of this scoring system have led to its
      implementation on a permanent basis. This is a U.S. government work. There are no
      restrictions on its use.

PMID- 11290990
TI  - Music and the PACU environment.
AB  - Pain is a common problem in the PACU, resulting in negative respiratory,
      cardiovascular, gastrointestinal, renal, neuroendocrine, and autonomic nervous
      system consequences for patients. Pain relief contributes to improved patient
      outcomes and is also an important component of patient satisfaction, particularly
      in light of today's environment of high competition among hospitals for patients.
      Music and quiet conversation by staff, contributing to low noise levels in the
      PACU environment, have the potential to provide pain relief and improve patient
      satisfaction with the PACU experience. This study investigated the effect of
      soothing music and lowering noise levels on the pain experience of patients
      during their PACU stay. A quasiexperimental study was conducted with 2 groups of
      patients, one who listened to music on a day when staff kept extraneous noise at
      a minimum in the PACU (the experimental group) and one who experienced the
      typical PACU day (the control group). The study was conducted at a large Veterans
      Administration hospital in the Midwest. The sample consisted of 97 individuals
      undergoing same-day surgery from all surgery services except open heart. Pain was
      measured by using the 11-point Numerical Rating Scale (NRS). The experimental
      group experienced a significant reduction in pain from admission to the PACU
      until discharge. There was no significant decrease for the control group.
      Approximately 65% of both groups reported no pain on admission to PACU. The
      percentage of those in the experimental group with no pain increased to 74% at
      time of discharge. The percentage of those in the control group who reported no
      pain on discharge had decreased to 58%. A total of 99% of the participants
      remembered their PACU stay. When asked to remember aspects of comfort during the
      PACU stay, the experimental group reported (1) significantly less noise caused by
      staff voices and equipment, (2) greater perception of availability of nurses, and
      (3) significantly more positive perception of their PACU stay. The study findings
      support the potential for music played throughout the PACU stay to positively
      affect the pain experience and improve comfort among patients having surgery.

PMID- 11290991
TI  - Strategic plan/planning strategically.

PMID- 11290992
TI  - Pain management: what do patients need to know and when do they need to know it?

PMID- 11290993
TI  - Take a bite out of high employee turnover.

PMID- 11290994
TI  - Evidence-based practice part 3: acute pain management of the perianesthesia
      patient.
AB  - Evidence exists that pain is inadequately controlled in most patients. This is
      caused, in part, by the fact that doctors and nurses have based clinical practice
      on myths and misconceptions about pain medications, rather than by using evidence
      based research. Evidence also exists that when pain is adequately controlled,
      there is greater patient satisfaction with care. The purpose of Part 3 in this
      series on pain is to review the literature on inadequate pain management, to
      review Joint Commission on the Accreditation of Healthcare Organizations (JCAHO)
      guidelines for correcting the inadequacy of pain control, and to review evidence
      based medications used for pain management.

PMID- 11290995
TI  - Notes from the 2000 American Society of Anesthesiologists Annual Meeting.

PMID- 11290997
TI  - The reputation of nurses: the good and the bad, but what about the truth?

PMID- 11290998
TI  - Brick by brick.

PMID- 11290999
TI  - Public policy: unintended consequences: an inherent risk in health policy
      development.

PMID- 11291000
TI  - Research: placebo: I will please (myself).

PMID- 11291001
TI  - Professional practice: supply is not the only answer.

PMID- 11291002
TI  - Technology: telehealth on the rise.

PMID- 11291003
TI  - Use of a faculty investment model to attain the goals of a college of nursing.
AB  - Driven by demands for fiscal prudence, new services, and an orderly transition as
      aging faculty approach retirement, a new model for administrative planning and
      decision making was tested. In its first year of using an investment model, a
      private, 600+ student, College of Nursing was able to achieve a labor savings of
      10 percent, an enhancement of revenue of 3 percent, and a human capital pool
      equal to 12 percent of total full-time faculty equivalents. The model, which
      includes the integration of strategic planning, benchmarking, continuous quality
      improvement, and management by objectives, was accomplished by taking three
      investment steps. The steps included goal determination, market understanding,
      and resource allocation. Investment activity distribution and work determination
      frameworks were developed as a result of the commitment to the investment
      process. Suggestions for the future include the need to continue to reorient
      administrative and faculty thinking as definitions of the educational enterprise
      evolve.

PMID- 11291004
TI  - Student civility in nursing programs: a national survey.
AB  - A survey of 611 nursing programs was performed to determine the extent to which
      certain problematic student behaviors existed in schools of nursing, and how they
      were being addressed. Participants were also asked about specific behaviors of
      current students compared with those of 5 years ago. Of the 611 surveys sent to
      program directors, 2 were undeliverable and 409 responded for a response rate of
      67 per cent. The majority of respondents (48.8 per cent) were from associate
      degree programs, followed by baccalaureate degree (43.9 per cent), and diploma
      programs (7 per cent). Three disruptive behaviors were identified by all
      respondents: inattentiveness in class, attendance problems, and lateness.
      Objectionable physical contact between students and instructors were identified
      by 24.8 per cent, and verbal abuse toward instructors in the clinical setting by
      42.8 per cent. Demographic variables examined in terms of their relationship to
      the behaviors included type of program, nursing program size, size of the parent
      institution, geographic region, location of program, and sponsorship of program.
      Administrators in different types of educational programs and from various
      geographic locations reported problematic student behaviors with high frequency.
      Identifying strategies for handling disruptive behaviors and assistance in
      implementing them is recommended along with a national forum to discuss the
      issue.

PMID- 11291005
TI  - Nursing doctoral program evaluation: Alumni outcomes.
AB  - Meaningful examination of program outcomes is one of the most challenging tasks
      facing faculty and administrators involved in the design and delivery of
      educational programs. This article reports the outcomes for one doctoral program
      in nursing and elucidates salient conceptual and methodologic issues in
      educational outcomes research for this discipline. Career development, scholarly
      productivity, and professional leadership were the foci of this outcomes study.
      Three instruments were used; data were provided by alumni, graduate faculty, and
      alumni supervisors. Data analysis techniques included content analysis and
      descriptive and correlational statistics. Results showed that graduates embarked
      on diverse career paths with the majority employed in academic institutions. Most
      graduates reported active involvement in research, publications, presentations,
      and professional leadership. Employment pattern differences were noted between
      academic year and summer-only program graduates with associated divergence in
      career emphasis, research productivity, and job satisfaction. A positive
      correlation of time since degree conferral with scholarly productivity and
      professional leadership was noted. Recommendations for future research include
      refining outcomes, linking process to outcome, using longitudinal designs, and
      attending to unique nursing student and doctoral program characteristics.

PMID- 11291006
TI  - A global health analysis project for baccalaureate nursing students.
AB  - This article describes an international nursing/global health analysis project
      that is completed in the U.S. classroom by baccalaureate nursing students.
      Project requirements, student activities, and course evaluation are described.
      Over a semester, student groups in the senior-level issues course use multiple
      resources (libraries, embassies, Internet, and personal contacts) to gather and
      analyze nursing and health care data on a self-selected International Council of
      Nursing (ICN) member country. At the end of the semester, student's synthesized
      materials are presented to classmates. A portfolio of materials is submitted and
      kept on file for multiple uses by faculty and students.

PMID- 11291007
TI  - Nursing students' use of a psychopharmacology game for client empowerment.
AB  - Theoretical support is evaluated for nursing students' use of an innovative
      educational intervention, the Psychopharmacology R.A.C.E. (Wissman and Tankel,
      Kansas City, MO) game, as an empowerment tool with mental health clients. Based
      on mutual trust and respect, the interpersonal process occurs between an
      individual or group (e.g., client, student) with a desire for competency growth
      (e.g., knowledge, proactive health behaviors, negotiation), and development of a
      sense of control and self-determination and another individual or group (e.g.,
      nurse) who serves as an enabler, supporter, and resource mobilizer. A review of
      empowerment literature identifies: (1) support of education as an empowerment
      tool; (2) identification of specific teaching methods and behaviors that promote
      empowerment; (3) empowerment as an outcome of involvement; and (4) support of the
      empowerment value of group participation. Preliminary clinical observations
      reveal strong support for nursing students' use of the Psychopharmacology
      R.A.C.E. game as a method to empower mental health clients.

PMID- 11291010
TI  - Learning disabilities: diagnostic considerations from an educational perspective.
AB  - This article reviews the current definitions of specific learning disability
      (LD). It describes the multiple causes among the specific learning disability
      (SLD) population, citing cognitive, neuroanatomical, cellular, and genetic
      research trends. Emphasis is placed on assessment components and processes,
      including typically used academic, cognitive, and neuropsychological measures and
      newly introduced dynamic or domain-based approaches. Researchers and
      practitioners now acknowledge that SLD represents a life-long condition,
      manifesting differently at each developmental stage. The impact of LD on adult
      adjustment and independence is described as the newest challenge in the field of
      LD research.

PMID- 11291011
TI  - Infantile autism: adult outcome.
AB  - Although the core features of autism do not change qualitatively, a gradual
      overall symptomatic improvement including an increase in adaptive skills is
      observed in most cases with age. Follow-up studies show that the diagnostic
      features, the differential diagnosis, and clinical problems of adult autistics
      differ substantially from that of autistic children. The differential diagnosis
      of older autistics include personality disorders, learning disabilities, and mood
      disorder. Depression, epilepsy, and behavioral problems such as aggression and
      agitation may be major clinical problems during adolescence. The early indicators
      of a better outcome include a higher level of IQ and language. Among the
      neuropsychological variables, measures of flexibility and cognitive shift are
      important as prognostic factors. Early behavioral and educational intervention
      may especially increase the adaptive skills of the patients and promote the in
      family communication. The outcome studies of autism are particularly helpful in
      addressing the appropriate and most effective programs of remediation for adult
      autistics.

PMID- 11291012
TI  - Selected neurodevelopmental delay syndromes and their impact on adult
      neuromaturation and adjustment.
AB  - A selective survey of neurodevelopmental delay syndromes is presented and
      discussed from neural, cognitive, and behavioral perspectives to highlight their
      impact on adult neuromaturation, learning abilities, psychosocial expression, and
      psychiatric adjustment. Emphasis is placed on the discussion of major factors and
      issues that influence neurodevelopmental delays, dysfunctions, and selective
      clinical examples of how they are manifested in adult adjustment.

PMID- 11291013
TI  - Neuropsychiatric implications and long-term consequences of fetal alcohol
      spectrum disorders.
AB  - Prenatal alcohol exposure can cause a whole spectrum of central nervous system
      (CNS) sequelae that persist throughout the life span and manifest in a spectrum
      of effects from clinically indistinguishable to severely impairing. The greatest
      impact of alcohol as a teratogen is to the brain-the greatest need is for
      holistic treatment and management of the associated mental disorders. The
      interaction of this subtle brain damage with the complex psychosocial
      circumstances surrounding the birth of a child to a mother with alcohol problems
      can further compound development and result in costly and devastating social
      consequences. Research is urgently needed on the chronic neuropsychiatric
      sequelae of these subtle birth defects of the brain. Identification of these
      fetal alcohol spectrum disorders (FASD) in the psychiatric nomenclature is a
      necessary step to focus the attention and resources of the mental health field on
      this personally and socially significant problem.

PMID- 11291014
TI  - Attention-deficit/hyperactivity disorder and learning disabilities in adults.
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) is a developmental disorder which
      begins in childhood. It is now recognized that ADHD persists into adolescence and
      adulthood in the majority of cases. Significant psychiatric comorbidity,
      particularly substance abuse, antisocial personality disorder, and mood and
      anxiety disorders occurs in adolescent and adult ADHD. Perhaps one fifth of
      childhood cases of ADHD may also have co-morbid learning disorder. Significant
      legal, academic, social, and occupational problems have been observed in adults
      with ADHD. The clinician faces a diagnostic and treatment challenge in trying to
      determine whether ADHD and learning disabilities (LDs) are present in the adult
      patient. Treatment and recommendations for accommodations in institutions of
      higher education and the workplace may rest on accurate discrimination between
      ADHD and LD.

PMID- 11291015
TI  - Nonverbal learning disability: adult outcomes.
AB  - There are few empirical studies of the adult outcomes of nonverbal learning
      disability (NLD). An overwhelming majority of NLD studies has been devoted to the
      nature of academic difficulties of school children, whereas the few follow-up
      studies have tended to be limited to college-age young adults. Herein, it is
      argued that the problems of adults with NLD do not fall solely in academic areas,
      and that early academic remediation programs might do well to include
      intervention in emotional and social skills enhancement.

PMID- 11291016
TI  - Adult outcomes of verbal learning disability.
AB  - Although it is currently generally accepted that, in most cases, verbal learning
      disability (VLD) can persist into adulthood, adult outcomes of learning
      disability are still under much discussion. The adult outcomes of two types of
      VLD (dyslexia and dysgraphia) will be the focus of this article. The defining
      characteristics of VLD and what constitutes these types of VLD are provided in
      detail elsewhere in this issue (see Jones and Eberling). This article will focus
      on the current epidemiology, possible causative factors, neurocognitive profiles,
      and neurological correlates of such disability. In addition, adult outcomes will
      be discussed for both those who succeed despite the disability and those who
      continue to struggle with the issues of VLD into adulthood. Specifically, factors
      that seem to contribute to success or struggle, and suggested treatments for VLD,
      will be discussed.

PMID- 11291017
TI  - Adult outcome of verbal learning disability: an optimistic note.

PMID- 11291018
TI  - Repetitive self-injurious behavior: a neuropsychiatric perspective and review of
      pharmacologic treatments.
AB  - The phenomenology, pathophysiology, and psychopharmacology of repetitive self
      injurious behavior (rSIB) are reviewed. Although numerous neurotransmitter
      systems are thought to be involved in the initiation and maintenance of rSIB, the
      majority of clinical studies attend to the role of serotonin or endogenous
      opioids. This focus has emerged from a conceptualization of rSIB as a problem of
      impulse control (primarily mediated by serotonin) and/or as a maladaptive pain
      related behavior (ultimately mediated by opioids). A developmental perspective of
      rSIB is emphasized, highlighting the biased prevalence of rSIB among patients
      with mental retardation and severe personality disorders and the significance of
      critical developmental events leading to pathology in "pedagogical" neural
      circuits. A novel typology is offered in an effort to better match interventions
      with rSIB subtypes. Achievement of this ultimate goal however, must await further
      research.

PMID- 11291019
TI  - Sleep in neuropsychiatric disorders.
AB  - Sleep disorders have been recognized for millennia as a common complication of
      medical and neurologic disease. Virtually all neuropsychiatric disorders carry
      with them the potential for disturbances of sleep. When such complications do
      exist, they are typically associated with decreased quality of life, increased
      morbidity, and, in some cases, increased mortality rates. The prevalence of major
      sleep disorders among neurologic patients is high, but the rate of detection and
      treatment is quite low. The major sleep-related problems in this population can
      be divided into six areas: insomnia, circadian rhythm (sleep-wake schedule)
      disorders, hypersomnia, sleep-related breathing disorders, motor disturbances in
      sleep, and parasomnias. In this brief review, general clinical principles,
      diagnostic assessment and management guidelines for each of these areas are
      considered and their specific manifestations in neuropsychiatric disorders
      identified.

PMID- 11291020
TI  - Pharmacologic approach to aggression in neuropsychiatric disorders.
AB  - Aggressive behavior has been associated with numerous neurologic conditions
      including traumatic brain injury, mental retardation, developmental disorders,
      Huntington disease, and several dementias. Preclinical and human studies suggest
      that dysfunction of neural systems involving the brainstem, hypothalamus,
      amygdala, or prefrontal cortex can give rise to aggression. Several
      neurochemicals are felt to be relevant to modulation of aggression, including
      serotonin, dopamine, norepinephrine, GABA, acetylcholine, and androgens.
      Pharmacologic intervention studies have targeted these systems but have been
      limited by inconsistent definitions of aggression and a relative paucity of
      controlled trials. This article briefly reviews studies of neural systems and
      medication trials relevant to aggression and propose a clinical approach to
      treatment of patients manifesting aggressive behavior.

PMID- 11291021
TI  - Pathophysiology and treatment of secondary obsessive-compulsive behaviors and
      tics.
AB  - Advances in neurobiological research suggest that certain frontal-subcortical
      circuits play important roles in idiopathic obsessive-compulsive disorder and
      Tourette's syndrome. Tics and obsessive-compulsive behaviors secondary to
      neurologic insult appear to involve the same neural circuitry. There are few
      systematic studies of the treatment of obsessive-compulsive behaviors and tics
      associated with neurologic disorders. However knowledge of the circuitry and
      associated neurochemistry of these disorders can help to outline a rational
      approach to these behaviors.

PMID- 11291022
TI  - Approaches to memory loss in neuropsychiatric disorders.
AB  - Many neuropsychiatric disorders affect memory. Brain regions important in the
      neuroanatomic substrate of memory include the hippocampus, and sections of the
      frontal, temporal, and parietal cortices and the thalamus. Acetylcholine and many
      other neurotransmitters and neuromodulators including dopamine, glutamate, GABA,
      the catecholamines, and estrogen modulate cognitive function. Treatment
      approaches to memory loss typically use Alzheimer's dementia as the template, and
      are discussed in this report.

PMID- 11291023
TI  - Disorders of sexual impulse control in neuropsychiatric conditions.
AB  - This article reviews hypersexuality in individuals with neuropsychiatric
      disorders and its psychopharmacologic treatment. A brief review of the neurology,
      neuroendocrinology, and neuropharmacology of sexual behavior is presented.
      Literature describing the occurrence and treatment of hypersexuality in
      individuals with neuropsychiatric disorders is reviewed along with literature
      which discusses the pharmacologic treatment of individuals with hypersexual
      disorders in nonneuropsychiatric populations. Finally, a clinical algorithm for
      approaching and treating such disorders in a neuropsychiatric population is
      presented.

PMID- 11291024
TI  - Apathy.
AB  - Deficits in motivated behavior are a very common sequela of most neuropsychiatric
      disorders, a source of significant disability to the individual, and a source of
      great frustration to their caregivers. Well-intentioned attempts to encourage
      certain activities in the apathetic patient often precipitate aggressive,
      dyscontrolled behavior. The psychopharmacologic approach to motivated behavior
      deficits is informed by the study of the components, circuitry, and
      neurochemistry of motivated behavior in animals and humans. This article
      selectively reviews this literature. The circuitry of motivated behavior involves
      a combination of behavior specific regions in the hypothalamus as well as a
      general reward system running from midbrain to forebrain and including important
      components of several frontal-subcortical circuits. Catecholaminergic systems,
      particularly the mesolimbic dopaminergic system, are key modulators of motivated
      behaviors. Treatment thus involves the use of catecholaminergic agents.

PMID- 11291025
TI  - Pharmacotherapy of disruptive behaviors associated with brain disease.
AB  - Disordered behavior resulting from central nervous system dysfunction is a common
      clinical problem for practitioners and for patients. Setting aside the problem of
      overtly aggressive, violent behavior, this article addresses the problem of
      disordered or disruptive behavior associated with neuropsychiatric conditions.

PMID- 11291026
TI  - The neuropsychiatry of pathologic affect: an approach to evaluation and
      treatment.
AB  - The ability to skillfully regulate the internal experience and outward expression
      of emotion is among the most complex and recently acquired functions of the human
      brain. When the capacity for emotional regulation is compromised by disease or
      injury the impact on individuals and their families may be considerable, both
      with regard to psychological well-being and social and occupational function.
      This article describes first a framework for the description, evaluation, and
      treatment of affective dysregulation. We review the literature regarding
      disorders of affective regulation, and in particular affective lability. Although
      disorders of affect as they occur in common neuropsychiatric disorders (eg,
      stroke, multiple sclerosis, traumatic brain injury, and so on) are the focus of
      this article, the review incorporates information from the study of patients with
      primary psychiatric disorders and hence the discussion herein may also be
      relevant to the understanding and treatment of affective lability in these
      conditions. An overview of the neurobiology that appears most relevant to
      understanding such problems is presented, along with several specific methods
      that appear to be useful in the evaluation of patients with affective lability.
      Finally, we review the literature regarding the treatment of disorders of affect
      and offer some practical suggestions for the treatment of patients with these
      problems.

PMID- 11291027
TI  - Influence of preculture on the prefreeze and postthaw characteristics of
      hepatocytes.
AB  - Recent studies performed in our laboratory have shown that a brief period of
      preculture prior to cryopreservation improves the postthaw viability of
      hepatocytes. The purpose of this investigation is to characterize specific
      metabolic and biochemical characteristics of the hepatocytes (both frozen and
      nonfrozen) to help elucidate the role of preculture on the postthaw viability.
      Fresh and thawed hepatocytes were cultured in a bioartificial liver (BAL) to
      determine albumin secretion as a function of time in culture. In addition, cell
      extracts were analyzed using nuclear magnetic resonance (NMR) spectroscopy to
      quantify changes in cell membrane composition and energetics as a function of
      time in culture prefreeze and postthaw. The results of these studies showed an
      increase in albumin concentration in the culture medium with time in culture for
      the period tested for both fresh and frozen and thawed hepatocytes. NMR
      spectroscopy of lipid extracts indicates that in vitro culture of hepatocytes
      results in an increase in cholesterol relative to membrane phospholipid.
      Moreover, the NMR results also indicate phospholipid interconversion, via
      specific lipases in cultured hepatocytes, and these changes are consistent with
      water permeability measurements performed previously. Significant changes in
      phosphoenergetics were also observed, with the net energy charge for the cells
      increasing significantly with time in culture. In addition, NMR spectra show
      increased levels of 6-phosphogluconate, another indicator of the cellular
      response to the stresses of isolation and ex vivo culture. These results suggest
      that energetic considerations may be a significant factor in the ability of
      hepatocytes to survive the stresses of freezing and thawing. Significant shifts
      in membrane phospholipids may also influence membrane permeability and postthaw
      survival.

PMID- 11291028
TI  - Overexpression of bcl-2 inhibits sodium butyrate-induced apoptosis in Chinese
      hamster ovary cells resulting in enhanced humanized antibody production.
AB  - Sodium butyrate (NaBu) can enhance the expression of genes from some of the
      mammalian promoters including cytomegalovirus (CMV) and simian virus 40 (SV40),
      but it can also inhibit cell growth and induce cellular apoptosis. Thus, the
      beneficial effect of using a higher concentration of NaBu on a foreign protein
      expression is compromised by its cytotoxic effect on cell growth. To overcome
      this cytotoxic effect of NaBu, a survival protein, human Bcl-2, was overexpressed
      in recombinant Chinese hamster ovary (CHO) cells (SH2-0.32), producing a
      humanized antibody directed against the S surface antigen of hepatitis B virus.
      When batch cultures of both control cells transfected with bcl-2-deficient
      plasmid (SH2-0.32-Deltabcl-2) and cells transfected with bcl-2 expression plasmid
      (14C6-bcl-2) were performed in the absence of NaBu, both cells showed similar
      profiles of cell viability and antibody production. Compared with the SH2-0.32
      Deltabcl-2 culture, under the condition of NaBu addition at the exponential
      growth phase, overexpression of the bcl-2 gene considerably suppressed the NaBu
      induced apoptosis of 14C6-bcl-2 by inhibiting caspase 3 activity and extending
      culture longevity by >2 days. As a result, the final antibody concentration of
      14C6-bcl-2 culture was twofold higher than that of SH2-0.32-Deltabcl-2 culture in
      the presence of NaBu and threefold higher than that of SH2-0.32-Deltabcl-2 and
      14C6-bcl-2 cultures in the absence of NaBu.

PMID- 11291029
TI  - Tracking lysozyme unfolding during salt-induced precipitation with hydrogen
      exchange and mass spectrometry.
AB  - We utilized electrospray ionization mass spectrometry (ESI-MS) and hydrogen
      deuterium exchange (HX) to detect unfolding of hen egg white lysozyme during salt
      induced precipitation. Deuterated lysozyme was dissolved in protonated buffer at
      pH 2.16 and precipitated with ammonium sulfate, sodium chloride, and potassium
      thiocyanate. ESI-MS was used to detect mass differences in lysozyme due to the
      loss of deuterons for solvent protons, providing insight on the conformational
      history of the protein during the labeling experiment. Precipitation with
      ammonium sulfate and sodium chloride did not unfold lysozyme, consistent with the
      known stabilizing effects of kosmotropic salts. Potassium thiocyanate, an
      aggressive chaotrope, was an effective precipitant at 0.2 M, but also disrupted
      lysozyme structure and caused the formation of precipitate fractions that did not
      readily redissolve into aqueous solution without the use of a chemical
      denaturant. Precipitation with 1.0 M thiocyanate resulted in faster rates of
      unfolding and larger amounts of the insoluble precipitate. The unfolding kinetics
      were biphasic, exhibiting a slow phase after a few hours that presumably
      reflected a smaller propensity for lysozyme to unfold in the precipitated state.
      Bimodal mass distributions in the ESI-MS spectra for the thiocyanate precipitates
      indicate two states for lysozyme in this system, a native and a molten globule
      like partially unfolded state. ESI-MS analysis of the insoluble precipitates
      indicated that they consisted primarily of protein molecules that had unfolded.
      Investigation of the HX behavior of lysozyme in a KSCN solution at low protein
      concentrations confirmed the destabilizing effect of the salt on the protein
      structure, even when there was almost no solid phase present. The HX/ESI-MS
      results provide insight into the mechanism combining precipitation and
      denaturation for such a system, both in terms of obtaining quantitative kinetic
      and stability information and the identification of the conformers present.

PMID- 11291030
TI  - Use of lipophilic anions for estimation of biomass and cell viability.
AB  - A method is described to estimate the microbial biomass of a sample, to enumerate
      the cells, and to distinguish the portion of metabolically active cells in the
      population by measuring the binding of phenyldicarbaundecaborane (PCB(-)) to the
      cells. This method can also be used for the analysis of a complex population of
      microorganisms if the cells composing the sample are sensitive to different
      biocidal agents. In addition, the analysis of PCB(-) binding is useful for the
      enumeration of the phage-infected cells and phage particles.

PMID- 11291031
TI  - Detection of toxic chemicals with high sensitivity by measuring the quantity of
      induced P450 mRNAs based on surface plasmon resonance.
AB  - In this study we describe a novel sensor system to detect toxic chemicals based
      on measurement of the quantity of Saccharomyces cerevisiae P450 mRNAs induced by
      them. Detection was conducted using a flow-injection-type sensor system based on
      surface plasmon resonance (SPR). The DNA and peptide nucleic acid (PNA) probes
      containing a complementary sequence to a part of P450 mRNA were immobilized on
      the sensor chip and the P450 mRNAs hybridized to the probes were quantified. We
      succeeded in detecting 10 ng/L (10 ppt) of atrazine using both DNA and PNA
      probes. Using this sensor system, we were able to detect bisphenol A in addition
      to atrazine. Furthermore, we achieved higher sensitivity by amplifying the target
      P450 mRNA based on nucleic acid sequence-based amplification (NASBA). This method
      allows for sensitive, rapid, and easy detection of some toxic chemicals.

PMID- 11291032
TI  - Use of the avidin (imino)biotin system as a general approach to affinity
      precipitation.
AB  - Affinity precipitation, especially secondary effect affinity precipitation, has
      repeatedly been suggested as a valuable technique for the biotechnical downstream
      process. The present lack of applications is related to the scarcity of
      predictable affinity macroligands and to the fact that rather high affinity
      constants are required in affinity precipitation (K(D) < 10(-10)). The latter are
      rarely found in nature, at least in the case of small affinity ligands (affinity
      tags), and are usually difficult to handle (complex dissociation) once one has
      found them. In this article we describe a new type of thermoresponsive affinity
      macroligand. The base polymer (poly-N-isopropylacrylamide, or PNIPAAm) is
      produced by chain transfer polymerization. As a consequence, the structure, as
      well as the solubility behavior, is very homogeneous (polydispersity < 1.2),
      whereas the average molecular mass is small (<5000 g/mol). In pure water, the
      base polymer shows sharp thermoprecipitation at 32.2 degrees C. Each oligomer
      carries a single amino end group, which allows easy and defined coupling of the
      affinity ligand, while preserving the ligand's activity to the highest possible
      degree. Herein, the oligomer was coupled to iminobiotin. The ensuing affinity
      macroligand has a high affinity to avidin (and avidin-tagged molecules) at
      elevated pH (<10), but releases the avidin easily at lower pH (approximately 4).
      The affinity macroligands were used to purify avidin from solutions containing
      large amounts of lysozyme as well as from cell culture supernatants containing 5%
      fetal calf serum. In both cases, pure avidin was recovered (residual protein
      contamination below the detection limit), with yields of >90%.

PMID- 11291033
TI  - Novel enzymatic approach to the synthesis of flavonoid glycosides and their
      esters.
AB  - Flavonoids such as (+)catechin can be efficiently solubilised in supersaturated
      solutions prepared with donor glycosides, e.g., p-nitrophenyl glycosides, di- and
      higher oligosaccharides, and poly(ethylene glycol) dimethyl ether in sufficiently
      high concentration for their efficient enzymatic glycosylation. Under these
      conditions several glycosidases readily accept (+)catechin as substrate and the
      target glycosides were prepared in one step in up to 26% yields. The
      regioselectivity of the reaction depends on the enzyme and substrate combination
      used; three positions, 5, 7, and 4', in the flavonoid can be glycosylated. The
      resulting and similar flavonoid glycosides were further modified by
      regioselective acylation with vinyl esters of arylpropenoic acids using lipases
      as biocatalyst. The efficiency of acylation was found to diminish in the order of
      vinyl cinnamate > vinyl ferulate > vinyl coumarate. This work demonstrates the
      feasibility of assembling complex flavonoid glycoside esters in just two steps by
      sequential use of commercially available glycosidases and lipases.

PMID- 11291034
TI  - Mechanism of charged pollutants removal in an ion exchange membrane bioreactor:
      drinking water denitrification.
AB  - The mechanism of anionic pollutant removal in an ion exchange membrane bioreactor
      (IEMB) was studied for drinking water denitrification. This hybrid process
      combines continuous ion exchange transport (Donnan dialysis) of nitrate and its
      simultaneous bioreduction to gaseous nitrogen. A nonporous mono-anion
      permselective membrane precludes direct contact between the polluted water and
      the denitrifying culture and prevents secondary pollution of the treated water
      with dissolved nutrients and metabolic products. Complete denitrification may be
      achieved without accumulation of NO3(-) and NO2(-) ions in the biocompartment.
      Focus was given to the effect of the concentration of co-ions, counterions, and
      ethanol on the IEMB performance. The nitrate overall mass transfer coefficient in
      this hybrid process was found to be 2.8 times higher compared to that in a pure
      Donnan dialysis process without denitrification. Furthermore, by adjusting the
      ratio of co-ions between the biocompartment and the polluted water compartment,
      the magnitude and direction of each individual anion flux can be easily
      regulated, allowing for flexible process operation and control. Synthetic
      groundwater containing 135-350 mg NO3(-) L(-1) was treated in the IEMB system. A
      surface denitrification rate of 33 g NO3(-) per square meter of membrane per day
      was obtained at a nitrate loading rate of 360 g NO3(-) m(-3)d(-1), resulting in a
      nitrate removal efficiency of 85%.

PMID- 11291035
TI  - Modeling, simulation, and optimization of bacterial leaching reactors.
AB  - Bacterial leaching represents an unusual problem in biochemical engineering,
      because the substrate for bacterial growth is not supplied directly, but is a
      product of another reaction, the leaching of mineral particles. In addition,
      leaching is a heterogeneous reaction dependent on the particle-size distribution
      in the feed and on the kinetics of particle shrinkage. In this study, these
      effects are incorporated in the material balance for each mineral by the number
      balance. Examination of the number balance gives rise to a novel analysis of the
      competing technologies for leaching. The model is completed by the addition of
      material balances for the ferrous and ferric ions, the dissolved oxygen, and for
      each bacterial species to the number balance for each mineral present in the
      feed. The model is compared with pilot plant data for three different ores. It is
      shown that the model is in excellent agreement with the data. The performance of
      a bacterial leaching reactor is explored using the model, and the washout and
      sensitivity criteria are determined. It is shown that there are three washout
      conditions, in which the leaching conversion drops to zero. The washout
      conditions are dependent on the growth rate of the bacteria, on the rate of
      dissolution of the mineral, and on the rate of mass transfer of oxygen to the
      reactor. The critical washout condition is that arising from the rate of mineral
      dissolution. The optimization of a plant in which continuous tank reactors are
      configured in series is addressed. This analysis shows that the primary reactor
      should be between 1.5 and 2 times the size of each of the secondary reactors in a
      series combination.

PMID- 11291036
TI  - Efficient selection of high-producing subclones during gene amplification of
      recombinant Chinese hamster ovary cells by flow cytometry and cell sorting.
AB  - The screening procedure for high-producing cell lines is extremely time- and
      labor-intensive and costly, and is at present guided by an empirical approach
      based on individual experience. Flow cytometry and cell sorting, with its ability
      to analyze and separate single cells, an ideal method in the selection of such
      rare cells. The isolation of recombinant cell lines is especially difficult due
      to repeated gene amplification, which introduces high mutational variation into
      the population. We have established and evaluated a modification of a previous
      method that traps secreted product on the surface of the secreting cell, thus
      allowing direct analysis of single cell specific production rates. This method
      was used to select for high-producing subclones of a recombinant Chinese hamster
      ovary (CHO) cell line producing a human antibody against HIV-1 by repeated rounds
      of gene amplification and cell sorting. This cell line has been amplified in
      previous investigations, so that the amount of work and testing required by
      traditional methods can be compared with the protocol described herein. Forty
      five 96-well plates were necessary to obtain a high-producing subclone by limited
      dilution methods, whereas only five plates were required when cell sorting was
      used. The specific production rate of the best clone obtained by sorting,
      however, was five times that of the clone obtained by traditional methods. In
      contrast to the clones obtained by limited dilution, which consisted of several
      populations of low- and high-producing cells even at high methotrexate
      concentrations (6.4 microM), the clones isolated by sorting were already
      homogeneous at 0.8 microM methotrexate.

PMID- 11291037
TI  - Modeling the kinetics of vinyl chloride cometabolism by an ethane-grown
      Pseudomonas sp.
AB  - Pseudomonas sp strain EA1 was isolated under aerobic conditions using ethane as
      the sole organic carbon and electron donor source, with an observed yield of 0.99
      mg total suspended solids/mg ethane (0.85 mg volatile suspended solids / mg
      ethane) and a maximum specific growth rate of 0.015 d(-1). When grown on ethane,
      EA1 cometabolizes vinyl chloride (VC) at a maximum rate of 0.350 micromol/mg
      volatile suspended solids/d and with a half saturation constant of 0.62 microM
      VC. The rate of VC use by EA1 is twice as high when ethane is also provided, even
      though consumption of ethane is almost completely inhibited until VC is consumed.
      The presence of ethane also reduces the total amount of VC cometabolized. A model
      was developed that adequately describes the batch kinetics of VC cometabolism in
      the presence and absence of ethane, as well as ethane metabolism in the presence
      and absence of VC. Terms are included that increase the initial rate of VC use in
      the presence of ethane (according to the ratio of initial ethane concentration to
      the half saturation coefficient) but decrease the total amount of VC
      cometabolized. Parameter estimates for the model were obtained using a step-wise
      experimental approach, with varying initial concentrations of VC and ethane.
      Strain EA1 completely dechlorinates VC in the presence and absence of ethane.
      Measurements of soluble chemical oxygen demand indicate that approximately 50% of
      the VC consumed is mineralized, with the balance released as soluble,
      nonchlorinated products. Ethene is not used as a substrate by EA1 but it does
      inhibit ethane metabolism and VC cometabolism. In mixtures containing all three
      compounds, more VC is degraded and at a faster rate compared to VC plus ethene.
      The results suggest that ethane-enhanced biodegradation of VC may contribute to
      VC removal at the aerobic fringe of groundwater plumes undergoing reductive
      dechlorination.

PMID- 11291038
TI  - Combining pathway analysis with flux balance analysis for the comprehensive study
      of metabolic systems.
AB  - The elucidation of organism-scale metabolic networks necessitates the development
      of integrative methods to analyze and interpret the systemic properties of
      cellular metabolism. A shift in emphasis from single metabolic reactions to
      systemically defined pathways is one consequence of such an integrative analysis
      of metabolic systems. The constraints of systemic stoichiometry, and limited
      thermodynamics have led to the definition of the flux space within the context of
      convex analysis. The flux space of the metabolic system, containing all allowable
      flux distributions, is constrained to a convex polyhedral cone in a high
      dimensional space. From metabolic pathway analysis, the edges of the high
      dimensional flux cone are vectors that correspond to systemically defined
      "extreme pathways" spanning the capabilities of the system. The addition of
      maximum flux capacities of individual metabolic reactions serves to further
      constrain the flux space and has led to the development of flux balance analysis
      using linear optimization to calculate optimal flux distributions. Here we
      provide the precise theoretical connections between pathway analysis and flux
      balance analysis allowing for their combined application to study integrated
      metabolic function. Shifts in metabolic behavior are calculated using linear
      optimization and are then interpreted using the extreme pathways to demonstrate
      the concept of pathway utilization. Changes to the reaction network, such as the
      removal of a reaction, can lead to the generation of suboptimal phenotypes that
      can be directly attributed to the loss of pathway function and capabilities.
      Optimal growth phenotypes are calculated as a function of environmental
      variables, such as the availability of substrate and oxygen, leading to the
      definition of phenotypic phase planes. It is illustrated how optimality
      properties of the computed flux distributions can be interpreted in terms of the
      extreme pathways. Together these developments are applied to an example network
      and to core metabolism of Escherichia coli demonstrating the connections between
      the extreme pathways, optimal flux distributions, and phenotypic phase planes.
      The consequences of changing environmental and internal conditions of the network
      are examined for growth on glucose and succinate in the face of a variety of gene
      deletions. The convergence of the calculation of optimal phenotypes through
      linear programming and the definition of extreme pathways establishes a different
      perspective for the understanding of how a defined metabolic network is best used
      under different environmental and internal conditions or, in other words, a
      pathway basis for the interpretation of the metabolic reaction norm.

PMID- 11291039
TI  - Controlling hyperhydration of carnations (Dianthus caryophyllus L.) grown in a
      mist reactor.
AB  - Carnations (Dianthus caryophyllus L.) grown in vitro often develop physiological
      abnormalities such as hyperhydration. The amount of hyperhydration and growth was
      compared between carnations grown in mist reactors and conventional semisolid
      micropropagation systems (vented or unvented GA7 culture boxes). Plants grown in
      the mist reactor with long misting times (10 min h(-1)) produced more dry mass
      than those grown with <10 min h(-1); however, more misting also produced more
      hyperhydrated plants (70% hyperhydration). Control of hyperhydration in the mist
      reactor involved either reducing the overall nutrient mist supply or altering the
      mist supply throughout the culturing period. Stepped decreases in the mist supply
      throughout the 3-week period or an overall decrease in the duration of misting
      reduced hyperhydration to 13% and 5%, respectively. However, for both misting
      regimes, the biomass of normal (healthy) plants (fresh and dry weights) was
      limited. Further analysis suggested that, although normal plant biomass increased
      with longer mist exposure, hyperhydration levels also increased while the water
      content, based on percent dry weight, approached that of hyperhydrated plants.
      Sufficient normal plant development (fresh weight, leaf and shoot numbers,
      height, and rooting) with < 50% hyperhydration was obtained by weekly, stepped
      increases in the nutrient mist supply.

PMID- 11291040
TI  - Potent inhibition of hemangiosarcoma development in mice by cidofovir.
AB  - The acyclic nucleoside phosphonate analogue cidofovir is a broad-spectrum anti
      DNA virus agent, which also possesses potent inhibitory activity against various
      tumors associated with papillomaviruses in animal models and patients. Moreover,
      we recently described the potent inhibition of polyomavirus (PyV)-induced
      hemangioma formation in rats by cidofovir. This activity could not be explained
      by an antiviral mechanism. We have now evaluated the effect of cidofovir on the
      growth of hemangiosarcomas originating from PyV-transformed (PV/2b/35) cells,
      which do not produce polyomavirus. In vitro, cidofovir proved to be cytostatic
      for PV/2b/35 cells at a 50% cytostatic concentration (CC(50)) of 2.3 microg/ml.
      At cidofovir concentrations > or =20 microg/ml, cytotoxicity due to induction of
      apoptosis was observed. In vivo, intratumoral therapy with cidofovir, at 100
      mg/kg 3 times a week, completely inhibited the development and even caused
      regression of established PV/2b/35 hemangiosarcomas in nude mice. Five days after
      the start of treatment, few proliferating cells were noted in the cidofovir
      treated tumors, whereas control tumors were characterized by high expression of
      proliferating cell nuclear antigen (PCNA). Moreover, cidofovir induced apoptosis
      in the hemangiosarcomas, as evidenced by Tunel (terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling) staining. Also after intraperitoneal
      administration, cidofovir afforded a prominent protection against the growth of
      intraperitoneally or intracerebrally inoculated hemangiosarcoma cells in SCID
      mice. In conclusion, cidofovir possesses a direct antitumor activity, which is
      mediated by induction of tumor cell apoptosis. Cidofovir should be further
      explored for its potential in the treatment of fast-growing vascular tumors, like
      hemangiomas and hemangiosarcomas.

PMID- 11291041
TI  - Interleukin-13 receptor as a unique target for anti-glioblastoma therapy.
AB  - Surgery, radiotherapy and chemotherapy have minimally altered survival of
      glioblastoma patients. We explored a specific approach for glioblastoma therapy
      in which cellular interleukin-13 (IL-13) receptors were targeted by an IL-13
      cytotoxin. A wide array of human glioblastoma cell lines expressing the receptor
      for IL-13 were effectively killed by an IL-13 cytotoxin, a chimeric protein
      composed of human IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13
      PE38QQR or IL-13 toxin). Daily (qd) intratumoral injections of IL-13 toxin (50
      and 100 microg/kg/day) for 5 consecutive days into subcutaneous human U251
      glioblastoma tumors (approx. 30 mm(2)) in nude mice resulted in complete
      regression of tumors in 4/5 and 5/5 mice, respectively. Tumor regression
      persisted for at least 221 days postimplantation. Three alternate day injections
      (qod) of IL-13 toxin (250 microg/kg/day) into other subcutaneous U87 glioblastoma
      tumors also produced durable complete responses (CR) in all 5 mice. Twice daily
      (bid) intraperitoneal injections of IL-13 toxin at 25 or 50 microg/kg/dose for 5
      days (total doses = 10) regressed U251 tumors by 45% and 58% with 1/5 and 2/5
      CRs, respectively, on day 54. Intraperitoneal administration of IL-13 toxin with
      an identical schedule at a dose of 50 microg/kg injected into mice bearing U87
      xenografts reduced tumor burden by one-half on day 36. Similar doses (25 or 50
      microg/kg) with a daily schedule (qd x 5) by the intravenous route also
      suppressed growth of U251 subcutaneous tumors by 75% and 81% with 1/6 CR in
      either group by day 34. All mice tolerated therapy well without any visible signs
      of toxicity. On the basis of these studies, we have initiated a Phase I clinical
      trial using IL13-PE38QQR in patients with recurrent glioblastoma. Published 2001
      Wiley-Liss, Inc.

PMID- 11291042
TI  - The pattern of metastasis of human melanoma to the central nervous system is not
      influenced by integrin alpha(v)beta(3) expression.
AB  - We investigated the effect of integrin alpha(v)beta(3) expression on the
      metastatic pattern of human melanoma cells in the central nervous system (CNS).
      For this purpose, we developed a hematogenous CNS melanoma metastasis model in
      nude mice using a modified internal carotid artery infusion technique. This
      protocol revealed 2 different patterns of CNS metastasis. The integrin
      alpha(v)beta(3)-expressing melanoma lines Mel57 and Zkr nearly exclusively
      produced metastases in the brain parenchyma, whereas cells of the BLM and MV3
      lines, devoid of integrin alpha(v)beta(3) expression, preferentially metastasized
      to dura mater and leptomeninges. Treatment with hyaluronidase to obtain single
      BLM cell suspensions did not influence the metastatic pattern, indicating that
      this was not simply the result of entrapment of tumor cell aggregates in large
      sized leptomeningeal vessels. The role of integrin alpha(v)beta(3) expression in
      the process of metastasis was tested by transfection of BLM, but did not lead to
      an altered pattern of metastasis. We did observe, however, slower growth of the
      transfected tumors, although the in vitro growth rate was unaltered, indicating a
      reduction in tumorigenicity. We conclude from our findings that CNS metastasis of
      melanoma cells in the mouse xenograft model occurs in at least 2 different but
      very reproducible patterns. Although it is predicted that adhesion of tumor cells
      to endothelial cells plays a role in this phenomenon, tumor cell integrin
      alpha(v)beta(3) expression per se does not explain the difference in metastatic
      behavior in the CNS. We assume that other, as yet unknown factors, must be
      involved.

PMID- 11291043
TI  - M(R) 77 KDA factor derived from fibroblasts stimulates the invasion ability of
      breast-cancer cells.
AB  - Breast-cancer cells frequently invade into the skin. However, few reports have
      described the mechanisms responsible for this invasion. In this study, we
      investigated the effects of skin fibroblasts on the invasion ability of breast
      cancer cells, using a modification of Boyden's chamber method, and purified an
      invasion-stimulating factor from fibroblasts. Conditioned medium of skin
      fibroblasts, DF-1, significantly stimulated the invasion ability of breast-cancer
      cells, OCUB-1. The invasion-stimulating factor produced from skin fibroblasts was
      then partially purified and characterized. The soluble invasion-stimulating
      factor of fibroblasts was a protein of 77 kDa, as calculated by SDS-PAGE.
      Although TGF-alpha and bFGF stimulated the invasion of OCUB-1, no inhibition of
      the 77 kDa factor was achieved with neutralizing antibodies against TGF-alpha and
      bFGF. These findings suggest that the 77 kDa factor derived from skin fibroblasts
      might be unique, might play an important role in invasion to the skin and might
      explain the frequent skin invasion in breast carcinoma.

PMID- 11291044
TI  - Multidrug resistance gene 1 expression in salivary gland adenocarcinomas and oral
      squamous-cell carcinomas.
AB  - In combined chemotherapy for head-and-neck cancer (HNC), salivary gland-cell
      adenocarcinoma (SGA) shows insufficient clinical outcome, and it has been
      suggested that the sensitivity and/or the mechanism of resistance to anti-cancer
      drugs are different between SGA and oral squamous-cell carcinoma (SCC). The aim
      of our study was to clarify whether P-glycoprotein (P-gp) expression is
      associated with multidrug resistance (MDR) in HNC and the difference in the
      process of its development between SGA and SCC. In immunohistochemical analysis,
      P-gp expression was found in the ductal cells of salivary glands but not in oral
      mucosal epithelium. In cancer tissues, a few SCC cells in 12 of 37 and most cells
      in all SGAs expressed P-gp. The intensive P-gp expression was significantly found
      in SGA compared with SCC. In an in vivo chemotherapeutic model using tumor
      bearing nude mice, P-gp expression in counterparts was observed in only a few
      cells of the HSY line, while no P-gp expression was observed in Hepd cells.
      However, P-gp expression was developed in both HSY and Hepd cell lines after
      vincristine (VCR) treatment. RT-PCR showed that the mean ratios of mdr1 mRNA
      expression levels in HSY clones were 3.7-fold higher than those in Hepd clones
      after VCR treatment, while each cell line exhibited both induction and activated
      production of P-gp. These results suggest that P-gp-related MDR in SGA is an
      inherent phenotype caused by both high levels of P-gp induction and activated P
      gp production during VCR treatment, while that in SCC is an acquired phenotype
      chiefly caused by induction of P-gp.

PMID- 11291046
TI  - Association of chronic lymphocytic leukemia with specific alleles of the HLA
      DR4:DR53:DQ8 haplotype in German patients.
AB  - The etiology of chronic lymphocytic leukemia (CLL) remains unknown, though a
      genetic susceptibility has been suggested. Results of complete DNA typing of HLA
      alleles in CLL patients are lacking. We compared HLA class I and class II
      frequencies in 101 German CLL patients and 157 healthy German controls as
      determined by PCR-SSP/SSO DNA analysis and serologic typing. The most striking
      difference was the increased frequency of HLA-DRB4*0103 [relative risk (RR) =
      2.74, p < 0.0025] among patients. The presence of alleles HLA-DRB1*0401, HLA
      DQB1*0302 and HLA-DPB1*0301 as well as of homozygosity for HLA-DQB1 was also
      associated with a higher risk for CLL, though none of these differences remained
      significant after correction for multiple comparisons. No association was found
      for any HLA class I allele. Haplotype analysis revealed a CLL-specific linkage
      disequilibrium for HLA-DRB1*0401:DRB4*0103 and HLA-DRB4*0103:DQB1*0302. Our
      results suggest that CLL could be associated with distinct class II alleles of
      the Caucasian haplotype HLA-DR4:DR53:DQ8, which has also been related to a
      susceptibility for several auto-immune diseases. The positive, though weak,
      association of CLL with HLA-DPB1*0301 might represent an independent
      susceptibility factor since no linkage disequilibrium existed with any of the
      other CLL-associated alleles. None of the previously reported associations with
      HLA class I antigens was confirmed. Our results suggest that factors within or
      close to the human MHC class II region confer susceptibility to CLL.

PMID- 11291045
TI  - Up-regulation of vaults may be necessary but not sufficient for multidrug
      resistance.
AB  - Vaults are ribonucleoprotein complexes comprised of the 100 kDa major vault
      protein (MVP), the 2 high m.w. vault proteins p193 (VPARP) and p240 (TEP1) and an
      untranslated small RNA (vRNA). Increased levels of MVP, vault-associated vRNA and
      vaults have been linked directly to non-P-glycoprotein-mediated multidrug
      resistance (MDR). To further characterize the putative role of vaults in MDR,
      expression levels of all of the vault proteins were examined in various MDR cell
      lines. Subcellular fractionation of vault particles revealed that all 3 vault
      proteins are increased in MDR cells compared to the parental, drug-sensitive
      cells. Furthermore, protein analysis of subcellular fractions of the drug
      sensitive, MVP-transfected AC16 cancer cell line indicated that vault levels are
      increased, in this stable line. Since TEP1 is shared by both vaults and the
      telomerase complex, TEP1 protein (and vault) levels were compared with telomerase
      activity in a variety of cell lines, including various MDR lines. Our studies
      demonstrate that while vault levels may be a good predictor of drug resistance,
      their up-regulation alone is not sufficient to confer the drug-resistant
      phenotype. This implies a requirement of an additional factor(s) for vault
      mediated MDR.

PMID- 11291047
TI  - Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic
      loss in early onset breast cancer.
AB  - Frequent allelic deletions at chromosome 11q24-q25 have been described in both
      early and late onset breast cancers, suggesting the existence of a gene locus
      implicated in the initiation and/or progression of the disease. In the present
      study we fine mapped this region further by loss of heterozygosity (LOH) analysis
      in a population of early onset breast cancer cases (n = 102, 22 to 36 years old).
      Loss of chromosomal material was assessed for possible association with patient
      survival as well as Nottingham histologic grade (NHG). Additionally, we
      investigated the involvement of the 11q24-q25 locus in a group of familial breast
      cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28
      to 40 years). Among the consecutive patients, extensive LOH was observed for all
      markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the
      D11S4125 marker was found to be associated with reduced survival (p = 0.026),
      whereas the adjacent D11S387 marker correlated with higher histologic grade (p =
      0.042). In the familial cases, the most telomeric markers showed substantially
      lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient
      groups demonstrated that this difference in LOH frequency was statistically
      significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p
      = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may
      harbor a gene implicated in early onset breast cancer. Our data suggest that the
      most probable position for this locus is defined by the markers D11S387 and
      D11S4125 and furthermore that it may play a less significant role in familial
      breast cancer cases not linked to either of the BRCA genes.

PMID- 11291048
TI  - Circulating tumor-derived DNA may permit the early diagnosis of head and neck
      squamous cell carcinomas.
AB  - A series of eight microsatellite loci were assayed for both loss of
      heterozygosity and new mutated alleles in 91 head and neck squamous cell
      carcinomas. In 58 cases, alterations were detected and used as markers for
      assaying the presence of circulating tumor-derived DNA in the patients' plasma.
      This was unambiguously detected in 17 cases. The probability of detecting
      circulating DNA was independent of tumor stage and was found to be present even
      in some individuals with stage I tumors. The presence of such DNA, however, could
      not be correlated with disease outcome or other significant clinical parameters,
      suggesting that it has no prognostic significance. The results indicate that
      circulating tumor-derived DNA could be used as a means of early diagnosis of head
      and neck tumors.

PMID- 11291049
TI  - Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen
      metabolizing enzymes and gene-environment interactions.
AB  - Breast cancer is the most frequent malignancy among women. Since genetic factors
      such as BRCA1 and BRCA2 as well as reproductive history constitute only 30% of
      the cause, environmental exposure may play a significant role in the development
      of breast cancer. Likewise, the relevant enzymes involved in the
      biotransformation of xenobiotics (from tobacco smoke, diet or other environmental
      sources) might play a role in breast carcinogenesis. Since individuals with
      modified ability to metabolize these carcinogens could have a different risk for
      breast cancer, we investigated the role of cytochromes P-450 (CYP1A1, CYP2D6),
      glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1,
      NAT2) gene variants in breast carcinogenesis. A case-control study was conducted
      on 149 women with breast carcinoma and 207 healthy controls, both of French
      Canadian origin. The CYP1A1*4 allele was found to be a significant risk
      determinant of breast carcinoma (OR = 3.3, 95% CI 1.1-9.7), particularly among
      post-menopausal women (OR = 4.0, 95% CI 1.2-13.8). The frequency of NAT2 rapid
      acetylators was increased among smokers (OR = 2.6, 95% CI 0.8-8.2), while the
      NAT1*10 allele conferred a 4-fold increase in risk among women who consumed well
      done meat (OR = 4.4, 95% CI 1.0-18.9). These data suggest that CYP1A1*4, NAT1 and
      NAT2 variants are involved in the susceptibility to breast carcinoma by modifying
      the impact of exogenous and/or endogenous exposures.

PMID- 11291050
TI  - Expression of Epstein-Barr virus in cutaneous T-cell lymphoma including mycosis
      fungoides.
AB  - Cutaneous T-Cell lymphoma (CTCL) is a non-Hodgkin's lymphoma of unknown
      pathogenesis. Mycosis fungoides (MF) is a clinically determined subset of CTCL
      with intensive infiltration of lymphoma cells into the epidermis. To determine
      whether Epstein-Barr virus (EBV) is associated with these lymphoma cells, we
      performed mRNA in situ hybridization in 5 cases of CTCL and 7 cases of MF using
      an RNA probe transcribed from BamHI W fragment of EBV genome. These transcripts
      were detected in the majority of lymphoma cells in all cases examined. We also
      detected intensive hybridization signals on epidermal squamous cells contiguous
      to strong infiltration with lymphoma cells into the subcutaneous connective
      tissue. Similarly, positive signals were detected using the probes transcribed
      from the sequences of EBV-encoded small nonpolyadenylated RNAs-1 (EBER1) and EBV
      determined nuclear antigen-2 (EBNA2). The EBNA2 latent membrane protein-1 (LMP1)
      and BZLF1 product (ZEBRA) were also detected by immunofluorescence staining using
      monoclonal antibodies. Further in the same experiment, we detected
      immunofluorescence of epidermal cells. EBV DNA was detected in all cases tested
      by DNA in situ hybridization. Moreover, we also identified the signals on
      epidermal cells via this technique. Polymerase chain reaction revealed amplified
      EBV DNA for most cases tested. Double staining with immunohistochemistry and RNA
      in situ hybridization showed that T-cell marker-positive cells, but not EBV
      carrying B-cells, exhibited signals for the EB viral RNA. These findings suggest
      that EBV is involved in the neoplastic transformation of CTCL and MF.

PMID- 11291051
TI  - Study on the role of G1 cyclins in Epstein-Barr virus-associated human lymphomas
      maintained in severe combined immune deficiency (SCID) mice.
AB  - Five Epstein-Barr virus (EBV)-positive human lymphoma cell lines maintained in
      severe combined immune deficiency (SCID) mice were used to investigate the role
      of G1 cyclins in EBV-induced lymphomagenesis. All the primary tumors had been
      negative for EBV but became positive after establishment in SCID mice, with
      monoclonal immunoglobulin gene rearrangement and EBV monoclonality. To compare
      the expression status of G1 cyclins, these EBV-associated lymphoma lines (6 EBV[
      ] human SCID mouse lymphoma lines, 13 human B cell lymphomas and 8 samples of
      human tonsil tissue) were examined by reverse transcription-polymerase chain
      reaction-Southern blotting, Western blotting and immunohistochemistry. mRNA
      expression of cyclin D1 (CCND1), cyclin D2 (CCND2), cyclin E (CCNE), cyclin
      dependent kinase 2 (CDK2) and 4 (CDK4) was found in all 3 types of lymphomas.
      Western blotting demonstrated identical results. Immunohistochemistry revealed
      CCND1 to be negative in all lymphomas. CCND2 was positive and restricted to the
      nuclei in all EBV(+) SCID mouse lymphoma lines, whereas it was limited to the
      cytoplasm in half of the EBV(-) counterparts. CCNE was positive in the nuclei in
      all EBV(+) but negative in all EBV(-) SCID mouse lymphoma lines.
      Immunoprecipitation of EBV(+) and (-) SCID mouse lymphomas for CCND1, CCND2 and
      CCNE vs. p21, PCNA and CDK2 or CDK4 demonstrated that, in EBV(+) SCID lines,
      CCND2/CDK4 complexes were present without binding to p21, suggesting independence
      from p21 regulation. In EBV(-) SCID mouse lymphomas, half of the cases showed
      complex formation of CCND2/CDK4 without binding of p21. In contrast, CCND1/CDK4
      and CCNE/CDK2 were under regulation of p21 in both EBV(+) and (-) lymphomas.
      These results suggest that differential expression of CCNDs, CCNE and CDKs, as
      well as variation in their subcellular localization and association with CDK
      inhibitor protein, could explain differences in cell proliferation between EBV(+)
      and EBV(-) lymphomas.

PMID- 11291052
TI  - Human antibody derivatives against the fibroblast activation protein for tumor
      stroma targeting of carcinomas.
AB  - The fibroblast activation protein (FAP) is selectively expressed on activated
      fibroblasts of the tumor stroma on more than 90% of lung, breast and colon
      carcinomas. The high prevalence and abundance of FAP(+) stroma make it a
      promising target for in vivo diagnosis and therapy of a variety of carcinomas. We
      describe the humanization of the murine FAP-specific MAb, F19, which has already
      been clinically used for in vivo diagnostic purposes. Using phage display
      technology and human V-repertoires, VL and VH regions of F19 were replaced by
      analogous human V-regions while retaining the original HCDR3 sequence in order to
      maintain F19 epitope specificity. The resulting human single-chain fragments of
      immunoglobulin variable regions (scFv 34, scFv 18) showed affinities of 6 nM on
      cell membrane-bound FAP. scFv 34 was expressed as a bivalent minibody (Mb 34).
      The antigen-binding characteristics of Mb 34 were comparable to the parental and
      a complementarity-determining region (CDR)-grafted version of F19. This was
      revealed by binding competition studies, FACS analyses and immunohistochemistry
      on various tumor samples including breast, colon and lung carcinomas.
      Importantly, compared with the CDR-grafted humanized scFv version of F19, the V
      regions of the selected human scFv 34 showed sequence identity with the parental
      antibody (Ab) only over the short, 15-amino acid long HCDR3. Thus, a largely
      reduced xenoantigenic potential is expected. These human Ab derivatives are
      suitable to develop novel therapeutic concepts with broad applicability for a
      wide variety of histological carcinomas based on tumor stroma targeting.

PMID- 11291053
TI  - Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over
      expression of the high-affinity receptor edg4 in differentiated thyroid cancer.
AB  - Lysophosphatidic acid (LPA) is a small lipid mediator with pleiotropic biological
      activities, e.g., the regulation of cellular proliferation and various aspects of
      cellular physiology. Signal transduction is achieved by binding to 2 high
      affinity receptors, EDG2 and EDG4, and a group of low-affinity receptors, EDG1-7,
      all belonging to the superfamily of G protein-coupled receptors. We examined the
      growth-regulatory effects of LPA in primary cultures of 8 goiters and 1 papillary
      thyroid cancer. We further assessed mRNA expression of high-affinity receptors
      EDG2 and EDG4 in 14 normal thyroids, 29 papillary thyroid cancers, 7 follicular
      thyroid cancers and 13 goiters by quantitative RT-PCR. We also identified mRNA
      expression of phospholipase A(2) and LPA acyltransferase in fresh thyroid tissues
      derived from various sources. At concentrations of 10, 50 and 150 microM, LPA
      induced a 2-fold rise of proliferation (p < 0.001) and acted as strongly as
      thyrotropin. The combination of LPA and TSH produced significant synergistic
      effects compared with each substance alone (p < 0.05). Normal thyroid, goiter and
      papillary or follicular thyroid cancer expressed 2 high-affinity cognate LPA
      receptors, EDG2 and EDG4. EDG4 receptor mRNA expression was increased 3-fold in
      differentiated thyroid cancer (p < 0.01), both papillary (p < 0.01) and
      follicular (p < 0.05), compared to normal thyroid or goiter. Overall expression
      of EDG2 receptor was unchanged in malignancy; however, increased EDG2 expression
      in individual samples correlated with lymphonodular metastasis (p = 0.01). Thus,
      lipid mediators are a novel class of factors involved in the control of
      proliferation in the human thyroid. Altered mRNA expression of the high-affinity
      LPA receptor EDG4 suggests a role in the pathogenesis of differentiated thyroid
      cancer.

PMID- 11291054
TI  - Inhibition of colon cancer metastasis by a 3'- end antisense urokinase receptor
      mRNA in a nude mouse model.
AB  - The role of urokinase-type plasminogen activator receptor (uPAR) in human colon
      cancer metastasis has not been tested using an antisense approach. In our study,
      the HCT116 cells, with high metastatic potential were transfected with expression
      vectors containing a 3' or 5' uPAR cDNA fragment in an antisense (AS)
      orientation. Transfection of 4 clones was confirmed by DNA hybridization
      analysis. Receptor-bound endogenous uPA activities of the clones were reduced to
      16-68% of controls. The extracellular matrix degradation by the 4 clones was
      decreased to 33-76%. Two of the clones, 3'-AS7 and 5'-AS, were evaluated in an in
      vivo assay system of experimental metastasis using athymic mice. Pulmonary
      metastases were found in 63-78% mice injected with the parent HCT116 or control
      cells. In mice injected intravenously with the antisense transfected clones, 3'
      AS7 and 5'-AS, however, pulmonary metastases were found in only 19% and 9%
      respectively (p < 0.05). These results provide direct evidence that both 3' and
      5'-AS uPAR can inhibit colon cancer invasion and metastasis and may offer the
      prospect of defining specific targets for gene therapy.

PMID- 11291055
TI  - I.V. Administration of L-GNRH-PE66 efficiently inhibits growth of colon
      adenocarcinoma xenografts in nude mice.
AB  - When developing new anti-cancer therapeutic treatments, it is crucial to find the
      correct route of administration and timetable for treatment. Recently, we
      constructed the L-GnRH-PE66 chimeric protein, which can target and kill
      adenocarcinoma cells both in vitro and in vivo. We examined the ability of the L
      GnRH-PE66 chimeric protein to inhibit tumor growth in colon carcinoma xenografted
      nude mice, using different routes of administration and various timetables of
      treatment. In addition, we examined the ability of the chimeric protein to
      inhibit tumor growth of large tumors that resemble those encountered in human
      patients in the clinical setting. We found that an i.v. dose of 12.5 microg given
      every 48 hr was the most efficacious in inhibiting tumor growth. Tumors treated
      with this concentration of the chimeric protein were 4.4 times smaller in volume
      and 3.4 times smaller in weight than those in the control groups. This protocol
      of L-GnRH-PE66 treatment is an improvement on our previously suggested treatment
      for adenocarcinoma in humans. An i.v. injection every 48 hr is effective, less
      toxic and less painful. Our results further support the use of L-GnRH-PE66 as an
      effective treatment for adenocarcinoma in humans.

PMID- 11291056
TI  - Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined
      with control of defecation in cancer patients.
AB  - It has been reported that 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy
      camptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxy-camptothecin
      (SN-38), have absorption characteristics of weakly basic drugs, suggesting that
      alkalization of the intestinal lumen might reduce reabsorption and its attendant
      side effects. Furthermore, stasis of stools containing these compounds is thought
      to induce damage to the intestinal mucosa. The prevention of CPT-11-induced side
      effects by oral alkalization (OA) combined with control of defecation (CD) was
      estimated in a case-control study of lung cancer patients. Coinciding with day 1
      of CPT-11 infusion and for 4 days thereafter, OA and CD were practiced utilizing
      orally administered sodium bicarbonate, magnesium oxide, basic water and
      ursodeoxycholic acid. OA involved the daily use of all four therapeutics, and CD
      required doses of up to 4.0 g/day of magnesium oxide and 2 L/day of excess basic
      water. From three ongoing prospective phase I/II studies, we selected 37
      consecutive patients who were treated with CPT-11 in combination with cisplatin
      in the presence of OA and CD (group B). Thirty-two control subjects who were
      matched to the background characteristics of the case patients were treated with
      the same regimen in the absence of OA and CD (group A). Toxicities induced by the
      CPT-11/cisplatin combination were evaluated and analyzed in group A and group B
      in a case-control format. The use of OA and CD resulted in significantly higher
      stool pH (p < 0.0001), while reducing the incidence of delayed diarrhea (> or =
      grade 2: group A 32.3% versus group B 9.4%; p = 0.005), nausea (p = 0.0001),
      vomiting (p = 0.001) and myelotoxicity, especially granulocytopenia (p = 0.03)
      and lymphocytopenia (p = 0.034). In addition, dose intensification was well
      tolerated in patients receiving OA and CD, allowing dose escalation from 35.6 +/-
      6.0 to 39.9 +/- 5.6 mg/m(2)/week (p < 0.001). Tumor response rates for non-small
      cell lung cancer were 59.3% (16/27 patients) in group B compared with 38.5%
      (10/26 patients) in group A. Multivariate analysis revealed that the risk of CPT
      11-induced delayed diarrhea greater than grade 2 was associated with OA and CD
      (odds ratio for delayed diarrhea, 0.14 with use of OA and CD; 95% confidence
      interval, 0.05 to 0.4; p = 0.0002) and age (odds ratio, 1.08 per increase in age;
      95% confidence interval, 1.02 to 1.15; p = 0.009). OA and CD appear to be useful
      in preventing the dose-limiting side effects of CPT-11 noted in clinical
      practice, mainly nausea, vomiting, granulocytopenia and especially delayed
      diarrhea. Risk factors statistically associated with delayed diarrhea include
      advanced age and the use of CPT-11 without OA and CD.

PMID- 11291057
TI  - Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic
      epithelial cells of the cervix uteri.
AB  - Cytological screening for cervical cancer or its precursors using Papanicolaou's
      smear test (Pap test) has been highly efficient to reduce the morbidity and
      mortality of cervical cancer. However, evaluation of the Pap test relies on
      subjective diagnostic parameters and is affected by a high rate of false-positive
      and false-negative results. More objective diagnostic parameters to identify
      truly dysplastic or neoplastic cells in cervical smears as well as in cervical
      biopsy samples would therefore avoid insecurity for many patients and the high
      screening costs associated with repeated testing. Cervical dysplasia is induced
      by persistent infections through high-risk types of human papillomaviruses
      (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of
      two viral oncogenes, E6 and E7, which both interact with various cell cycle
      regulating proteins. Among these is the retinoblastoma gene product pRB, which is
      inactivated by E7. pRB inhibits transcription of the cyclin-dependent kinase
      inhibitor gene p16(INK4a). Increasing expression of the viral oncogenes in
      dysplastic cervical cells might thus be reflected by increased expression of
      p16(INK4a). In line with this hypothesis, we observed marked overexpression of
      p16(INK4a) in all cervical intraepithelial neoplasm (CIN) I lesions (n = 47)
      except those associated with low-risk HPV types (n = 7), all CIN II lesions (n =
      32), all CIN III lesions (n = 60) and 58 of 60 invasive cervical cancers. In
      contrast, no detectable expression of p16(INK4a) was observed in normal cervical
      epithelium (n = 42), inflammatory lesions (n = 48) and low-grade cervical lesions
      (CIN I) associated with low-risk HPV types (n = 7). Dysplastic cells could also
      be identified in cervical smears using a specific p16(INK4a) monoclonal antibody.
      These data demonstrate that p16(INK4a) is a specific biomarker to identify
      dysplastic cervical epithelia in sections of cervical biopsy samples or cervical
      smears.

PMID- 11291058
TI  - HPV16 L1E7 chimeric virus-like particles induce specific HLA-restricted T cells
      in humans after in vitro vaccination.
AB  - Cervical cancer has been shown to be highly associated with human papillomavirus
      (HPV) infection. The viral oncogenes E6 and E7 are constantly expressed by the
      tumor cells and are therefore targets for immunotherapy. In the present study we
      investigated the potential of HPV16 L1E7 chimeric virus-like particles (CVLP) to
      activate specific cytotoxic T lymphocytes in human blood donors. CVLP were
      expressed by recombinant baculovirus and purified. Direct incubation of freshly
      isolated peripheral blood lymphocytes (PBL) with CVLP resulted in induction of
      proliferation and growth of T cell lines. To enhance antigen presentation we also
      loaded dendritic cells with CVLP and used them to activate naive T cells. Growing
      cell lines were mainly CD3 positive (>95%) with a predominant CD4-positive and a
      minor CD8-positive component. Analysis of Tcell specificity was carried out by an
      interferon-gamma ELISpot assay. Dendritic cells pseudoinfected with CVLP or
      pulsed with human leukocyte antigen (HLA)-A*0201-restricted peptide E7(11-20) or
      with a newly identified HPV16 peptide L1(323-331) were used as stimulator cells.
      T cells responsive to CVLP were found in the cultures with frequencies of 0.5%
      0.7%. Frequencies to peptides were around 0.1%. These T cells had cytolytic
      activity toward autologous B-lymphoblastic cell lines either pseudoinfected with
      CVLP or pulsed with HLA-A*0201-restricted peptides. They also lysed the HPV16-
      and HLA-A*0201-positive cervical cancer cell line CaSki, whereas HLA-A*0201
      negative SiHa cells were not lysed. We conclude from our data that CVLP show
      promise for a therapeutic vaccine in patients with HPV16-positive cervical
      intraepithelial neoplasia lesions or cervical cancer.

PMID- 11291059
TI  - Study of human leukocyte antigen class I phenotypes in Moroccan patients with
      nasopharyngeal carcinoma.
AB  - Previous reports demonstrated an association between the human leukocyte antigen
      (HLA) and risk for nasopharyngeal carcinoma (NPC) among the Chinese in Singapore,
      a population with a high incidence of this malignancy. In our study, we assess
      the association between HLA and NPC in Morocco, a median-prevalence area for this
      cancer, where NPC presents the particularity of also affecting young individuals.
      Using the standard microlympho-cytotoxicity test, we typed a total of 154
      Moroccan NPC patients and 257 unrelated healthy controls for their HLA-A and B
      antigens. The results of these analyses show that the frequencies of HLA-A10, HLA
      B13 and HLA-B18 were found to be higher in the NPC group than in the control
      group, whereas HLA-A9 was associated with a decreased risk. After correction for
      the number of specificities tested, these differences were statistically
      significant only for HLA-B18 (corrected p value [pc] < 0.023, relative risk [RR]
      = 4.14) and HLA-A9 (pc < 0.023, RR = 0.45). The comparison of the distribution of
      the HLA antigens in younger and older cohorts of patients shows that the
      incidence of HLA-A10 and HLA- B18 was higher in the older group, whereas the
      frequencies of HLA-A19 and HLA-B13 were significantly higher in younger patients
      compared with controls. The presence of both HLA-A19 and HLA-B13 phenotypes
      correlated with an increased risk of developing NPC among overall patients
      compared with controls. According to the sex distribution, increased frequency of
      HLA-B18 was found in male and female NPC patients compared with controls, whereas
      the frequency of HLA-A10 was higher only in male NPC patients compared with
      controls.

PMID- 11291060
TI  - Dietary catechins and epithelial cancer incidence: the Zutphen elderly study.
AB  - The flavonoids, a group of more than 4,000 polyphenolic antioxidants, are
      potential cancer preventive components of fruits and vegetables. Catechins, one
      of the 6 major groups of flavonoids, are present in high concentrations in tea as
      well. Our objective was to evaluate the association between intake of catechins
      and incidence of epithelial cancers with data from the Zutphen Elderly Study, a
      prospective cohort study among 728 men aged 65-84 years in 1985. The average
      catechin intake at baseline was 72 mg/day (range, 0-355 mg/day). After 10 years
      of follow-up, 96 incident epithelial cancers were recorded, including 42 cases of
      lung cancer. After multivariate adjustment, catechin intake was not associated
      with epithelial cancer (risk ratio [RR] from lowest to highest tertile: 1.00,
      0.75, 0.94; p for trend: 0.82), or lung cancer (RR from lowest to highest
      tertile: 1.00, 0.72, 0.92; p for trend: 0.80). Catechins not from tea were
      borderline significantly inversely associated with lung cancer incidence (RR and
      95% confidence interval [CI] for a 7.5-mg increase in intake: 0.66, 0.42-1.05),
      whereas catechins from tea were not. Catechins from apple, the major source of
      non-tea catechins, were also related to lung cancer incidence (RR and 95% CI for
      a 7.5-mg catechin increase: 0.67, 0.38-1.17). Because tea, the major catechin
      source in this population, was not associated with cancer risk, it seems unlikely
      that catechins are responsible for the observed inverse trend between non-tea
      catechins and lung cancer incidence. However, differences in bioavailability of
      the various catechins may play a role; effects on individual cancer sites cannot
      be excluded and merit further investigation.

PMID- 11291061
TI  - Diverging breast cancer mortality rates in relation to screening? A comparison of
      Nijmegen to Arnhem and the Netherlands, 1969-1997.
AB  - Age-standardised breast cancer mortality rates have been stable for decades.
      However, rates have started to decline in several Western countries. In countries
      where population-based screening programmes for breast cancer were introduced in
      the late 1980s or early 1990s, the key question now is to what extent screening
      is responsible for the reported declines in mortality. This study compares breast
      cancer mortality rates in Nijmegen, where a screening programme for breast cancer
      was introduced in 1975, to a control city, Arnhem, and to the Netherlands as a
      whole over a 20-year period. Age-standardised breast cancer mortality rates as
      well as age-standardised mortality ratios were calculated for successive calendar
      years from 1969 to 1997. Further, a tailor-made period-cohort-group Poisson
      regression model was fitted. Figures displaying age-standardised mortality rates
      and ratios showed inconclusive patterns with regard to the expected impact of
      screening. Depending on when mortality rates were allowed to deviate between
      populations, the period-cohort-group analysis indicated a non-significant 6% to
      16% reduction in breast cancer mortality after 2 decades in favour of the
      Nijmegen female population. Possible explanations are discussed as to why the
      mortality reductions reported by randomised trials might not be observed in a
      public health screening programme, such as the Nijmegen programme, evaluated by
      comparisons of geographical trends.

PMID- 11291062
TI  - Resistance to CD95-mediated apoptosis in breast cancer is not due to somatic
      mutation of the CD95 gene.
AB  - Resistance to CD95 (Apo-1/Fas)-mediated apoptosis is a typical feature of breast
      cancer cells. Recent studies identified deleterious mutations of the CD95 gene
      not only in a variety of B cell lymphomas but also in a number of solid tumor
      entities. Therefore, we amplified and sequenced selected regions of the CD95 gene
      from 48 breast cancer cases and 10 cell lines but no mutation was found. In the
      presence of both polymorphic alleles, loss of heterozygosity was excluded in 27
      informative cases. We conclude, that relevant somatic mutations of the CD95 gene
      occur, if at all, at a low frequency and are not the primary cause for resistance
      to CD95-mediated apoptosis in breast cancer.

PMID- 11291063
TI  - Murine models for experimental therapy of pediatric solid tumors with poor
      prognosis.
AB  - Novel therapeutic strategies are required for pediatric solid tumors with poor
      prognosis such as metastasizing neuroblastoma, rhabdomyosarcoma and Ewing's
      sarcoma. A prerequisite for the development of such new therapies is the
      availability of murine models. To be useful for therapeutic studies, these models
      should not only recapitulate the genetic alterations characteristic of the human
      disease but should also mimic the metastatic process and the response to current
      therapy, both of which ultimately determine the fate of children with these
      tumors. This review scrutinizes the utility of existing murine models of
      neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma for investigating novel
      therapies. Much experience has been gained with both syngeneic and xenogeneic
      transplantable models of these tumors, while transgenic and knockout mice are
      just beginning to be available for therapeutic investigations. Modeling the
      genetic aberrations characterizing these tumors may provide faithful models for
      therapeutic studies in the future.

PMID- 11291064
TI  - Mitochondrial DNA alteration in esophageal cancer.
AB  - It has been reported that various cancers frequently have mutations in the D-loop
      region of mitochondrial DNA (mtDNA). We examined the genetic alterations in this
      region of esophageal cancer using direct sequencing. Of 68 sequence variants, 15
      have not been reported to date. Tumor mtDNA with these variants were compared
      with mtDNA from corresponding normal esophageal mucosa. Two of 37 primary
      esophageal cancers (5%) contained somatic mutations in the D-loop region of
      mtDNA. Although the mutation rate of mitochondrial tumor DNA within the D-loop
      was not high, this result suggested that mtDNA mutations play a role in the
      development of esophageal cancer.

PMID- 11291065
TI  - Quantitative expression profile of androgen-regulated genes in prostate cancer
      cells and identification of prostate-specific genes.
AB  - Quantitative expression profile of androgen-regulated genes (ARGs) was evaluated
      in the hormone-responsive prostate cancer cell line LNCaP by serial analysis of
      gene expression (SAGE). A total of 83,489 SAGE tags representing 23,448 known
      genes or expressed sequence tags (ESTs) and 1,655 potentially novel sequences
      have unraveled the transcriptome of LNCaP cells, the most common cell line used
      in prostate cancer research. Comparison of transcripts between control and R1881
      treated LNCaP cells revealed the induction of 136 genes and repression of 215
      genes in response to androgen (p < 0.05). Strikingly, a high fraction (
      approximately 90%) of ARGs identified in our study has not been described as ARGs
      previously. A number of prostate-specific transcription factors were among the
      ARGs identified here. Classification of the ARGs on the basis of biochemical
      functions revealed that a great majority of ARGs identified in our experimental
      system appear to be involved in regulation of transcription, splicing, ribosomal
      biogenesis, mitogenesis, bioenergetics and redox processes. One of the novel
      aspects of androgen signaling included androgen regulation of genes involved in
      DNA repair/recombination process. By comparing our LNCaP-C and LNCaP-T SAGE
      libraries with SAGE tag libraries available at the NCBI-SAGE website, we have
      identified >200 potential prostate specific/abundant transcripts. The discovery
      of new prostate-specific genes and ARGs provides a unique opportunity to
      determine the role of these genes in prostate cell growth, differentiation and
      tumorigenesis.

PMID- 11291066
TI  - Khat (Catha edulis) consumption causes genotoxic effects in humans.
AB  - We used the micronucleus (MN) test to determine the genetic damage caused by
      khat, a widely consumed psychostimulant plant, in exfoliated cells of volunteers
      who chewed the drug on a regular basis. In the first study in which we compared
      the frequency of MN in buccal and bladder mucosa cells in 20 khat consumers (10
      160 g/day) and 10 controls, a pronounced (8-fold) increase in micronucleated
      buccal mucosa cells was seen among khat consumers; khat consumption did not lead
      to a detectable elevation of micronucleated bladder mucosa cells. Among heavy
      khat chewers, 81% of the MN had a centromere signal indicating that khat is
      aneuploidogenic. To investigate the effect of simultaneous consumption of tobacco
      and alcoholic beverages, we compared the MN frequency in buccal cells of 25 khat
      consumers (20-85 g/day) who smoked cigarettes (15-60/day) and drank alcoholic
      beverages (15-80 g of pure ethanol/day) with a control group (control group I) of
      25 individuals matched for age, body weight, tobacco and alcohol consumption and
      with another control group of 25 individuals (control group II) not consuming any
      of the drugs. The frequency of buccal mucosa cells with MN was higher in control
      group I than in group II and the effect of khat, tobacco and alcohol was found to
      be additive. A time-kinetics study on khat-induced MN showed that the highest
      frequency of MN was observed during the fourth week after consumption. In light
      of the large body of evidence on the close association between genetic damage and
      cancer, these results suggest that khat consumption, especially when accompanied
      by alcohol and tobacco consumption, might be a potential cause of oral
      malignancy.

PMID- 11291068
TI  - p53 Mutations are present in colorectal cancer with cytoplasmic p53 accumulation.
AB  - Previous studies have shown that nuclear p53 over-expression is an indicator of
      p53 mutations whereas cytoplasmic p53 accumulation is related to wild-type p53 in
      several kinds of tumors. Cytoplasmic p53 accumulation has been demonstrated to be
      an independent prognostic factor in colorectal adenocarcinomas. The purpose was
      to examine whether mutations occur in cases with p53 accumulated in the cytoplasm
      and whether there are any differences in the frequency and characteristics of p53
      mutations in different staining patterns. In the present study, we identified p53
      mutations using PCR single-strand conformation polymorphism (SSCP) and DNA
      sequencing in 75 primary colorectal adenocarcinomas with different staining
      patterns (negative, nucleus, cytoplasm, nucleus and cytoplasm). The results show
      that the frequency and nature of mutations in tumors with cytoplasmic p53
      accumulation were similar to those with nuclear p53 expression. However, the
      tumors with accumulation in both the nucleus and cytoplasm demonstrated a higher
      mutation rate. We suppose that the role of cytoplasmic p53 accumulation in
      predicting prognosis in patients with colorectal cancer may be dependent on both
      mutational and non-mutational mechanisms.

PMID- 11291067
TI  - Catechol estrogens induce oxidative DNA damage and estradiol enhances cell
      proliferation.
AB  - Estrogen-induced carcinogenesis involves enhanced cell proliferation (promotion)
      and genotoxic effects (initiation). To investigate the contribution of estrogens
      and their metabolites to tumor initiation, we examined DNA damage induced by
      estradiol and its metabolites, the catechol estrogens 2-hydroxyestradiol (2
      OHE(2)) and 4-hydroxyestradiol (4-OHE(2)). In the presence of Cu(II), catechol
      estrogens formed piperidine-labile sites at thymine and cytosine residues in
      (32)P 5'-end-labeled DNA fragments and induced the formation of 8-oxo-7,8-dihydro
      2'-deoxyguanosine. NADH markedly enhanced Cu(II)-dependent DNA damage mediated by
      nanomolar concentrations of catechol estrogens. Catalase and bathocuproine
      inhibited the DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). These
      results suggest that H(2)O(2), generated during Cu(II)-catalyzed autoxidation of
      catechol estrogens, reacts with Cu(I) to form the Cu(I)-peroxide complex, leading
      to oxidative DNA damage, and that NADH enhanced DNA damage through the formation
      of redox cycle. To investigate the role of estrogens and their metabolites in
      tumor promotion, we examined their effects on proliferation of estrogen-dependent
      MCF-7 cells. Estradiol enhanced the proliferation of MCF-7 cells at much lower
      concentrations than catechol estrogens. These findings indicate that catechol
      estrogens play a role in tumor initiation through oxidative DNA damage, whereas
      estrogens themselves induce tumor promotion and/or progression by enhancing cell
      proliferation in estrogen-induced carcinogenesis.

PMID- 11291069
TI  - Effect of dietary GLA+/-tamoxifen on the growth, ER expression and fatty acid
      profile of ER positive human breast cancer xenografts.
AB  - Gamma linolenic acid (GLA) possesses a number of selective anti-tumour properties
      including modulation of steroid receptor structure and function. We have
      investigated the effect of dietary GLA on the growth, oestrogen receptor (ER)
      expression and fatty acid profile of ER+ve human breast cancer xenografts.
      Experimental diets A, B, C, D were commenced after subcutaneous implantation of
      40 female nude mice with the MCF-7 B1M cell line (Group A = control diet: B =
      control diet + GLA supplement: C = control diet + tamoxifen: D = control diet +
      GLA + tamoxifen; 10 mice/group). The mice were terminated when tumour cross
      sectional area reached 250 mm(2). ER H-scores were assessed by
      immunohistochemical assay and fatty acid profiles by gas-liquid chromatography of
      termination tumour samples. Groups C and D displayed significantly slower tumour
      growth (p =.0002, p =.0006) with trend for slower growth in B (p =.065) compared
      to control Group A. ER was significantly reduced in all groups compared to A (p
      <.0001) with Group D (combined therapy) displaying markedly lower ER expression
      than with either therapy alone (p =.0002). There were significantly raised levels
      of tumour GLA and metabolites in the two groups (B and D) receiving GLA (p
      <.0001). This xenograft model of ER+ve breast cancer has demonstrated
      significantly lower tumour ER expression in those groups receiving GLA, an effect
      which appears to be additive to the reduced ER expression resulting from
      tamoxifen alone. The effects of GLA on ER function and the possibility of
      synergistic inhibitory action of GLA with tamoxifen via enhanced down-regulation
      of the ER pathway require further investigation.

PMID- 11291070
TI  - MedB-1, a human tumor cell line derived from a primary mediastinal large B-cell
      lymphoma.
AB  - Primary mediastinal B-cell lymphoma is a locally highly aggressive but poorly
      disseminating tumor composed of medium sized or large cells most probably of
      thymic medullary origin. It has a mature B-cell phenotype, typically lacks
      immunoglobulin expression and has variable defects in expression of HLA
      molecules. We present here a cell line, MedB-1, derived from such a tumor. As is
      frequently found in mediastinal B-cell lymphomas in situ, MedB-1 is CD10(-),
      CD19(+), CD21(-), CD22(+), CD23(+), CD25(-), CD37(+), CD38(-), CD39(+), CD40(+),
      CD54(+), CD95(+). Like the parental tumor, MedB-1 lacks HLA-A,B,C alpha-chains
      and beta(2)microglobulin and expresses HLA-D molecules at decreased levels. Both
      parental tumor and MedB-1 cells are clonally related as shown by immunoglobulin
      heavy chain gene rearrangement analysis. Unlike the parental tumor tissue, the
      MedB-1 cell line cytoplasmically expresses IgG/kappa in a very small subset of
      cells under standard culture conditions. MedB-1 does not contain any Epstein-Barr
      virus DNA. In a tissue adhesion assay MedB-1 cells showed an extensive binding to
      the medullary region of normal thymus. Altogether, MedB-1 is a suitable tool for
      functional and molecular analysis of this distinct lymphoma entity.

PMID- 11291071
TI  - Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB
      rearrangement.
AB  - Dermatofibrosarcoma protuberans (DP) is a skin tumor of intermediate malignancy
      characterized by high recurrence rates, for which surgical excision is the main
      therapy. All DP cases carry a specific t(17;22) translocation, resulting in a
      COL1A1/PDGFB rearrangement. The subsequently deregulated production of PDGFB
      generates autocrine stimulation of PDGFrbeta, leading to malignant
      transformation. Using NIH-3T3 cells transformed by the COL1A1/PDGFB rearrangement
      (5A cell line), we explored the possibility of blocking the PDGFB autocrine loop,
      both in vitro and in vivo, using STI571, an inhibitor of the PDGF receptor and of
      ABL kinase activity. The presence of small amounts of serum in the culture medium
      was required for the in vitro growth and morphological transformation of 5A
      cells. In the presence of STI571, the growth rate was reduced and the associated
      transformed phenotype changed to a flattened one. This effect could be reversed
      on removal of the inhibitor. The growth rate of tumors induced by 5A cells in
      nude mice was reduced by STI571 administration. Interestingly, this effect was
      also evident on pre-existing tumors, but no tumor eradication was observed. This
      is consistent with the reversible effects of the inhibitor observed in vitro but
      differs from the eradication effect of STI571 on BCR-ABL-induced tumors. Our data
      indicate that STI571 might be a candidate compound for the pharmacological
      treatment of DP and demonstrate that the same compound may act in different ways
      (cytotoxic vs. cytostatic), according to the specificity of the inhibited
      tyrosine kinase, namely, ABL or PDGFrbeta.

PMID- 11291072
TI  - Pancreatic cancer cell-derived vascular endothelial growth factor is biologically
      active in vitro and enhances tumorigenicity in vivo.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator that
      acts by binding to high-affinity transmembrane receptors. Although both VEGF and
      its receptors are overexpressed in human pancreatic ductal adenocarcinoma (PDAC),
      this malignancy is not generally considered to be highly vascular. It is not
      known, therefore, whether the abundance of VEGF in PDAC is biologically relevant.
      To address this issue, we measured the angiogenic effects of pancreatic cancer
      cell-derived VEGF in an in vitro endothelial cell proliferation assay and
      characterized the consequences of suppressing VEGF expression on pancreatic tumor
      growth in an athymic nude mouse model. We found that human pancreatic cancer cell
      lines secrete large quantities of biologically active VEGF into conditioned
      medium (CM). Stable transfection of an anti-sense VEGF(189) (AS-VEGF(189))
      expression construct into PANC-1 pancreatic cancer cells resulted in decreased
      VEGF expression and secretion, a decreased capacity of the resultant CM to
      enhance endothelial cell proliferation and a significant attenuation of tumor
      cell proliferation in vitro. Furthermore, when injected into athymic nude mice,
      AS-VEGF(189)-expressing cells exhibited an 80% decrease in tumor growth compared
      with control cells. These results support the hypothesis that VEGF promotes
      pancreatic cancer growth in vivo and suggest that anti-VEGF therapy may be useful
      in the treatment of this disease.

PMID- 11291073
TI  - Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal
      instability in human breast cancers.
AB  - Over-expression of a centrosomal serine/threonine kinase, STK15/BTAK, induces
      centrosome amplification, which results in chromosomal instability (CIN) in cell
      culture. In the present study, we investigated the correlation of STK15/BTAK mRNA
      expression with CIN and various clinicopathological factors in human breast
      cancer. STK15/BTAK mRNA levels were quantified by real-time PCR, and CIN values
      were determined by FISH analysis of chromosomes 1, 11 and 17 using centromeric
      probes. STK15/BTAK mRNA levels (0.310 +/- 0.413, mean +/- SD, n = 47) in breast
      cancers were significantly (p < 0.01) higher than those in normal breast tissues
      (0.044 +/- 0.029, n = 9). Furthermore, breast cancers were divided into 3 groups
      (low, intermediate and high) according to STK15/BTAK mRNA expression levels. CIN
      values of the low-expression group (27.9 +/- 12.6%, n = 18) were significantly (p
      < 0.01) higher than those of normal breast tissues (9.2 +/- 2.6%, n = 6), and
      those of the high-expression group (38.0 +/- 12.7%, n = 14) were significantly (p
      < 0.05) higher than those of the low-expression group. STK15/BTAK mRNA expression
      showed a significant (p < 0.05) correlation with high histological grade and
      negativity of estrogen and progesterone receptors. Our results demonstrate that
      STK15/BTAK mRNA is over-expressed in the majority of breast cancers and its over
      expression is significantly associated with CIN, implicating STK15/BTAK in
      carcinogenesis through induction of CIN. STK15/BTAK mRNA levels might be useful
      as an indicator of poor prognosis and resistance to endocrine therapy.

PMID- 11291074
TI  - Fibroblast growth factor-binding protein expression changes with disease
      progression in clinical and experimental human squamous epithelium.
AB  - Basic fibroblast growth factor (bFGF) is synthesized by a wide variety of normal
      and malignant cells. However, bFGF cannot exert its effects unless it gets
      outside of the cell. Since it lacks a signal sequence to direct secretion, the
      method by which cells release it remains unclear. A 17 kDa secreted binding
      protein for bFGF (FGF-BP, HBp-17) is expressed at high levels in squamous cell
      carcinoma (SCC) and transformed keratinocytes and may act as a chaperone to
      transport bFGF outside of the cell. In our study, FGF-BP mRNA expression in
      normal keratinocytes was higher than in 5/5 SCCs. Using a new monoclonal
      antibody, we demonstrate that FGF-BP can dimerize. Immunoassays demonstrate that
      normal keratinocytes have a higher level of FGF-BP than SCCs. In normal human
      squamous epithelium, we observed diffuse, moderate to intense cytoplasmic and
      membranous expression of FGF-BP. Expression decreased and became focal with
      disease progression to invasive cancer. Injection of immortalized but non
      tumorigenic HaCaT cells transduced with FGF-BP into normal human skin xenografts
      failed to result in tumors. Transfection of FGF-BP into the SCCs Det 562 and FaDu
      did not promote tumor growth more than controls, and peri-tumoral microvessel
      density was lower in FGF-BP-transfected than in control tumors. Taken together,
      these data suggest that FGF-BP expression in squamous epithelium does not play an
      important role in progression to invasive carcinoma.

PMID- 11291075
TI  - Up-regulation of MUC1 in mammary tumors generated in a double-transgenic mouse
      expressing human MUC1 cDNA, under the control of 1.4-kb 5' MUC1 promoter sequence
      and the middle T oncogene, expressed from the MMTV promoter.
AB  - In this study we examined the regulation of expression of the human MUC1 gene in
      vivo, by developing MUC1 transgenic mice. The data showed that epithelial
      specific expression of MUC1 can be directed by just 1.4 kb of 5' flanking
      sequence using MUC1 cDNA as a reporter gene in vivo. Furthermore, high levels of
      MUC1 expression were seen in the lactating mammary gland and in spontaneous
      mammary tumors generated by crossing the MUC1 transgenics with mice transgenic
      for the polyoma middle T oncogene under the control of the mouse mammary tumor
      virus promoter. This pattern of expression in epithelial tissues is comparable to
      the expression of MUC1 in humans and also to the expression pattern in another
      transgenic mouse line developed with a 10.6-kb genomic MUC1 fragment. This study
      confirmed that MUC1 is a compact gene and demonstrated that the 1.4-kb 5'
      sequence not only directs epithelial-specific expression of MUC1 in vivo but also
      contains the elements governing the up-regulation observed during lactation and
      in malignancy.

PMID- 11291076
TI  - Up-regulation of a novel mRNA (NY-CO-1) involved in the methyl 4-methoxy-3-(3
      methyl-2-butenoyl) benzoate (VT1)-induced proliferation arrest of a non-small
      cell lung carcinoma cell line (NSCLC-N6).
AB  - It is now well known that treatment of tumors, especially non-small-cell lung
      cancer (NSCLC), remains limited and it is urgent to develop strategies that
      target tumor cells and their genetic features. In this regard, our work is about
      genetic modifications arising in an in vitro NSCLC cell line after treatment with
      a chemical substance, methyl 4-methoxy-3-(3-methyl-2-butenoyl) benzoate (VT1).
      First, we showed that VT1 induces arrest of proliferation by blocking cells in
      the G1 phase of the cell cycle. Second, we use "differential display" strategy to
      clarify the genetic mechanisms involved in this proliferation arrest. A novel
      mRNA, NY-CO-1 (New-York Colon 1), of unknown function showed up-regulated
      expression after treatment. Application of "antisense" strategy confirmed this
      novel mRNA induction was effectively linked to growth arrest. Therefore, these
      data provide new information about mechanisms participating in arrest of
      proliferation of tumor cells and open new ways of treatment to target tumor
      growth.

PMID- 11291077
TI  - MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non
      hereditary endometrial hyperplasia and cancer.
AB  - The predictive value of MLH1 or MSH2 protein expression for the presence of
      truncating germline mutations was examined in benign and (pre)malignant
      endometrial samples from 3 patient groups: (I) 10 endometrial cancer patients
      from hereditary non-polyposis colorectal cancer (HNPCC) families with (n = 6) or
      without (n = 4) a known germline mutation; (II) 15 women from HNPCC families with
      (n = 7) or without (n = 8) a known germline mutation, who underwent endometrial
      sampling for non-malignant reasons; (III) 38 endometrial cancer patients <50
      years of age, without HNPCC family history. Immunostaining for MLH1 and MSH2 was
      performed on paraffin-embedded sections. In group III, tumor DNA was examined for
      microsatellite instability (MSI) and MLH1, MSH2 and MSH6 mutation analysis was
      carried out. In 6/6 MLH1/MSH2 mutation carriers with endometrial cancer (group
      I), concordance was found between protein loss in the tumor and the corresponding
      mutation. In 3 MLH1 mutation carriers, MLH1 protein loss was also observed in
      concurrent endometrial hyperplasia. In group II, no protein loss was detected in
      normal endometrial tissue samples; in 3/4 patients with endometrial hyperplasia,
      MLH1/MSH2 protein loss was observed. In group III, protein loss was detected in
      12/38 patients (9 MLH1, 3 MSH2), while in 3/11 patients with concurrent
      endometrial hyperplasia protein loss was also observed in the hyperplasia. MSI
      analysis in group III revealed 26 MSI-low and 12 MSI-high tumors. Mutation
      analysis in 28/38 patients showed only 1 missense MSH6 and no MLH1 or MSH2
      germline mutations. In group III, loss of MLH1/MSH2 protein expression was not
      related to the presence of MSI or MLH1/MSH2 germline mutations. In conclusion,
      MLH1 or MSH2 protein loss in HNPCC-related endometrial neoplasia is strongly
      related to corresponding germline mutations. This relation was not clearly
      present in young sporadic endometrial cancer patients. Immunohistochemical pre
      screening of the MLH1 and MSH2 proteins in endometrial hyperplasia or cancer can
      thus be helpful in HNPCC families. Frequent loss of MLH1 or MSH2 protein in
      endometrial hyperplasia indicates that this loss is an early event in endometrial
      carcinogenesis.

PMID- 11291078
TI  - Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the
      breast.
AB  - The cell-cell adhesion receptor gene E-cadherin (CDH1) is expressed by epithelial
      cells, in which it mediates adhesion and morphogenesis. Invasive lobular
      carcinoma (ILC) characteristically infiltrates diffusely as single cells; by
      immunohistochemistry, many of these tumours lack E-cadherin expression. In the
      present study we investigated various ways in which loss of function of the E
      cadherin gene could occur in ILCs, namely, promoter methylation, mutation and
      allelic loss. We analysed 22 ILCs and found 12 (55%) E-cadherin-negative samples
      by immunohistochemical analysis. Methylation-specific polymerase chain reaction
      (PCR) showed that 17/22 (77%) of these tumours had methylation of the CDH1
      promoter, including 11/12 (91%) of the E-cadherin-negative tumours. All 16 exons
      of E-cadherin (including intron-exon boundaries) were amplified from chromosomal
      DNA and screened for mutations by conformation-sensitive gel electrophoresis
      (CSGE). Bands with altered mobility were analysed by direct sequencing. We
      identified five frameshift mutations, which resulted in downstream stop codons
      and one splice site mutation in six different tumours (29%). Loss of
      heterozygosity (LOH) was assessed using microsatellite markers, and 9/18 (50%)
      informative tumours showed LOH. We conclude that most ILCs show genetic or
      epigenetic changes affecting the E-cadherin gene and that many of these tumours
      lack E-cadherin expression. In all cases in which there was loss of expression,
      this was consistent with biallelic inactivation of CDH1 by promoter methylation,
      mutation or allelic loss in any combination.

PMID- 11291079
TI  - Frequent allelic loss at 10q23 but low incidence of PTEN mutations in Merkel cell
      carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare, highly metastatic skin tumor of
      neuroectodermal origin. The disease shares clinical and histopathological
      features with small cell lung carcinoma (SCLC). The genetic mechanisms underlying
      the development and tumor progression of MCC are poorly understood. We recently
      showed by comparative genomic hybridization (CGH) that the pattern of chromosomal
      abnormalities in MCC resembles that of SCLC. One of the most frequently observed
      losses involved the entire chromosome 10 or partial loss of the chromosome 10
      long arm (33% of examined MCC cases). The PTEN tumor-suppressor gene has been
      mapped to 10q23.3 and was shown to be mutated in a variety of human cancers
      including SCLC. Germline PTEN mutations have been observed in familial
      predisposing cancer syndromes including Cowden disease. Interestingly, an
      association between Cowden syndrome and Merkel cell carcinoma has been reported.
      To study the possible role of PTEN in MCC oncogenesis, loss of heterozygosity
      (LOH) analysis for the 10q23 region was performed on 26 MCC tumor samples from 23
      MCC patients. The PTEN locus was deleted in 9 of 21 (43%) informative MCC tumor
      samples [7 of 18 (39%) MCC patients]. Despite this high frequency of LOH at
      10q23, mutation and homozygous deletion screening of the PTEN gene revealed only
      one tumor with a nonsense mutation and a second with a homozygous deletion of
      exon 9. These data suggest that either alternative mechanisms lead to
      inactivation of the PTEN gene or that other tumor-suppressor genes at chromosome
      10 are implicated in the development of MCC.

PMID- 11291080
TI  - Human anti-idiotypic antibodies can be good immunogens as they target FC
      receptors on antigen-presenting cells allowing efficient stimulation of both
      helper and cytotoxic T-cell responses.
AB  - Anti-idiotypic antibodies that mimic tumour-associated antigens can stimulate
      anti-tumour T-cell responses. In this article, we have studied the role of Fc in
      the presentation of T-cell epitopes by 2 anti-idiotypic antibodies, 105AD7 and
      708. The human monoclonal antibody 105AD7, which mimics CD55, stimulated strong
      in vitro T-cell proliferation, gammaIFN secretion and redirected cytotoxicity in
      unprimed T cells from healthy donors. However, removal of the Fc region of the
      anti-idiotype reduced the sensitivity of the assay 1,000-fold, as did inhibiting
      Fc uptake of the anti-idiotype by an excess of human IgG. The mouse anti-idiotype
      708, which mimics CEA, failed to stimulate in vitro T-cell responses on unprimed
      T cells from healthy donors. However, when a human IgG1 Fc region replaced its
      mouse Fc region, the anti-idiotype induced T-cell proliferation, gammaIFN
      secretion and redirected cytotoxicity in lymphocytes from unimmunised donors.
      Human anti-idiotypes are therefore good immunogens since they target Fc receptors
      on antigen-presenting cells, allowing efficient stimulation of both helper and
      cytotoxic T-cell responses. The immunogenicity of other anti-idiotypes may
      therefore be enhanced by human Fc targeting of antigen-presenting cells.

PMID- 11291081
TI  - Anti-tumor effects of human peripheral gammadelta T cells in a mouse tumor model.
AB  - Peripheral gammadelta T cells derived from healthy donors were found to exhibit
      cytotoxicity against a variety of tumor cell lines in vitro, including CNE2,
      which was established from nasopharyngeal carcinoma (NPC). The anti-tumor effects
      were further studied in a mouse model. Control nude mice inoculated s.c. with 5 x
      10(6) CNE2 cells regularly developed hypodermal tumors, which progressively
      increased in size, and animals had a mean survival of 35 +/- 3.4 days. Tumor
      growth was arrested and tumor size was reduced after animals were infused with 5
      x 10(7) gammadelta T cells derived from a healthy donor. The anti-tumor effects
      were temporary, however, and tumor growth was resumed after about 1 week in a
      group of the animals that had been given a single dose of gammadelta T cells. In
      another group of animals given 2 doses of gammadelta cells 1 week apart,
      resumption of tumor growth was delayed for a further week. Mean survival of the 2
      groups was increased to 61 +/- 15.7 and 74 +/- 12.9 days, respectively.
      Immunohistology revealed an accumulation of infused cells in tumors attended by
      focal tumor necrosis in specimens taken 2 days after infusion. Infiltrative cells
      virtually disappeared from tumor tissues 6 days after infusion, accompanied by
      increased mitotic indices of tumor cells. These temporal relationships suggested
      that the accumulation of infused gammadelta T cells in hypodermal tumors was
      responsible for the observed anti-tumor effects.

PMID- 11291082
TI  - Growth inhibition of human mammary carcinoma by liposomal
      hexadecylphosphocholine: Participation of activated macrophages in the antitumor
      mechanism.
AB  - This study was undertaken to investigate the antitumor effect of liposomal
      hexadecylphosphocholine (L-HPC), a synthetic phospholipid encapsulated into
      multilamellar vesicles (MLV). The effect of these liposomes was tested in an
      orthotopic nude mouse model using the human mammary carcinomas MDA-MB 435 and
      231. The main interest of the investigation was to study whether activated
      macrophages are substantially involved in the tumor growth inhibition mechanism.
      The growth of both MDA-MB 435 and 231 tumors in the mammary fat pad was
      significantly inhibited by a 14-day intraperitoneal therapy with L-HPC. The
      remaining tumors were shown to be heavily infiltrated with macrophages. In vitro
      studies of mPEM demonstrated a significant induction of macrophage-mediated tumor
      cytotoxicity (MMCTX) against the 2 cell lines by L-HPC. The L-HPC-mediated
      activation mechanism was characterized to be IL-6 and TNFalpha dependent but
      rather independent of IL-1alpha and nitric oxide (NO). NMA, a specific inhibitor
      of NO production, did not inhibit L-HPC-induced MMCTX. Furthermore, L-HPC was
      shown to upregulate the matrixmetalloproteinases MMP-9 and MMP-2 secretion into
      the supernatant. Considering cytokine release and production of collagenases, the
      L-HPC-induced macrophage activation cascade is assumed to be comparable with that
      of classical activators such as lipopolysaccharide (LPS) and interferon (IFN)
      gamma. As far as NO production is considered, the L-HPC activation mechanism
      differs from that caused by LPS and IFN gamma.

PMID- 11291083
TI  - Antitumor effect of a new selective matrix metalloproteinase inhibitor, MMI-166,
      on experimental pancreatic cancer.
AB  - The antitumor effect of a new matrix metalloproteinase inhibitor, MMI-166, which
      is a selective inhibitor of MMP-2 and -9, was examined in the hamster pancreatic
      cancer cell line PGHAM-1. In vitro, MMI-166 inhibited the gelatinase activity of
      MMP-2 and -9 derived from PGHAM-1 cells, and dose-dependently inhibited invasion
      of PGHAM-1 through a basement membrane-like barrier. MMI-166 showed no apparent
      cytotoxicity to PGHAM-1 cells in culture at 100 microgram/ml. MMI-166 (200 mg/kg)
      or vehicle were administered orally, once daily, from day 1 until day 21 after
      implantation in the orthotopic implantation model of PGHAM-1. MMI-166
      significantly reduced the incidence of liver surface metastasis from 66.7% to
      20.0%, and it reduced the number of liver surface metastases per animal from 6.17
      to 2.00, but this reduction was not significant. MMI-166 significantly reduced
      the volume of pancreatic tumors from 718.3 +/- 220.0 mm(3) to 222.8 +/- 85.4
      mm(3). Treatment of pancreatic tumors with MMI-166 caused a significant reduction
      in the microvessel density from 37.90 +/- 10.18/mm(2) to 16.16 +/- 3.15/mm(2) and
      a significant increase in apoptotic index from 1.75 +/- 0.41% to 3.96 +/- 0.38%,
      but there was no significant difference between tumor cell proliferation in the
      MMI-166-group and the control group. These results showed that selective MMP
      inhibition could limit both cancer spread and angiogenesis in pancreatic cancer.
      The selective MMP-2 and -9 inhibitor MMI-166 may be of therapeutic use in the
      treatment of pancreatic cancer because of its inhibitory effect on invasion and
      angiogenesis.

PMID- 11291084
TI  - Intradermal ras peptide vaccination with granulocyte-macrophage colony
      stimulating factor as adjuvant: Clinical and immunological responses in patients
      with pancreatic adenocarcinoma.
AB  - K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and
      induction of immunity against mutant ras can therefore be of possible clinical
      benefit in patients with pancreatic cancer. We present data from a clinical phase
      I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by
      i.d. injection of synthetic mutant ras peptides in combination with granulocyte
      macrophage colony-stimulating factor. Forty-eight patients (10 surgically
      resected and 38 with advanced disease) were treated on an outpatient basis.
      Peptide-specific immunity was induced in 25 of 43 (58%) evaluable patients,
      indicating that the protocol used is very potent and capable of eliciting immune
      responses even in patients with end-stage disease. Patients followed-up for
      longer periods showed evidence of induction of long-lived immunological memory
      against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also
      present in the tumor could be isolated from a tumor biopsy, demonstrating that
      activated, ras-specific T cells were able to selectively accumulate in the tumor.
      Vaccination was well tolerated in all patients. Patients with advanced cancer
      demonstrating an immune response to the peptide vaccine showed prolonged survival
      from the start of treatment compared to non-responders (median survival 148 days
      vs. 61 days, respectively; p = 0.0002). Although a limited number of patients
      were included in our study, the association between prolonged survival and an
      immune response against the vaccine suggests that a clinical benefit of ras
      peptide vaccination may be obtained for this group of patients.

PMID- 11291085
TI  - Enhancement of sensitivity to capecitabine in human renal carcinoma cells
      transfected with thymidine phosphorylase cDNA.
AB  - The purpose of the present study was to examine directly the role of thymidine
      phosphorylase (TP) in the sensitivity of renal cell carcinoma (RCC) to a novel
      fluoropyrimidine carbamate, capecitabine. TP cDNA-transfected RCC are used in
      these experiments to provide a basis for improved therapeutic benefit in
      chemoimmunotherapy. Human RCC line KU2 cells were transfected with
      pcDNA3.1/zeo(+) with or without human TP cDNA by the lipofectin method. We
      established a clone transfected with pcDNA3.1/zeo(+)/TP (KU2-TP15) and a clone
      transfected with pcDNA3.1/zeo(+) as a control (KU2-C1). TP expression levels
      (mean +/- SD) examined by enzyme-linked immunosorbent assay (ELISA) were 1.3 +/-
      0.14 U/mg protein in KU2, 1.6 +/- 0.57 U/mg protein in KU2-C1 and 216 +/- 25.6
      U/mg protein in KU2-TP15. Immunohistochemical staining of subcutaneous tumors
      established in Balb/c nu/nu mice showed that KU2-TP15 was strongly positive for
      TP expression, whereas KU2 and KU2-C1 were negative. Sensitivities in vitro to 5
      fluorouracil (5FU), 5'-deoxy-5-fluorouridine (5'DFUR) and capecitabine in KU2
      TP15 were significantly enhanced compared with those in KU2 or KU2-C1. A moderate
      but statistically significant bystander effect was observed in vitro. KU2-TP15
      tumors showed significant increase in the in vivo sensitivities to 5'DFUR and
      capecitabine as compared with the vehicle alone while KU2-C1 tumors did not. The
      difference in tumor-free rate in mice bearing KU2-TP15 at 2 months after the
      cessation of treatment was statistically significant between the capecitabine
      treatment group and the controls, the 5FU treatment group and the 5'DFUR
      treatment group. The present study clearly provides direct evidence for the role
      of TP in mediating the sensitivity of RCC to capecitabine.

PMID- 11291086
TI  - Trends in the incidence of cutaneous malignant melanoma in New South Wales, 1983
      1996.
AB  - The incidence of cutaneous malignant melanoma (CMM) has been rising in fair
      skinned populations throughout the world for decades. The upward trend may,
      however, finally be slowing in some of these populations. Recent (1983-1996) CMM
      incidence trends for a high incidence area (New South Wales, Australia) have been
      examined according to gender, age group, body site and tumour thickness. Despite
      continuing upward trends in older age groups, particularly among men (e.g., 7.20%
      increase per year in men aged 75+), incidence for younger ages is stabilizing (in
      men) or declining (in women): average annual percentage changes of -3.03 and 
      0.88 were observed for women aged 15-34 and 35-54, respectively. Patterns suggest
      a birth-cohort effect, with those born since 1945 or 1950 having lower (females)
      or similar (males) rates to those born earlier. For each gender, all-ages
      incidence rose by a similar amount for each of the main body sites except the leg
      in women, where incidence fell by 0.49% per year. In men, the incidence of both
      thin (</=75 mm) and thick (>75 mm) melanomas increased (significantly, by 2.63%
      per year and non-significantly, by 0.93% per year, respectively) between 1989 and
      1996. In women, incidence remained stable for both thickness subgroups. These
      data are consistent with a stabilization or reduction in either total sun
      exposure or intermittency of exposure among New South Wales cohorts born since
      about 1950. Because incidence rates are still much higher than they were a few
      decades ago, however, efforts to reduce sun exposure, particularly in children
      and youth, must continue.

PMID- 11291087
TI  - Plasma prolactin and prostate cancer risk: A prospective study.
AB  - Prolactin, a pituitary peptide hormone with multiple effects, stimulates prostate
      growth in experimental models. In humans, prolactin receptors are present in the
      prostate and are particularly abundant in pre-cancerous lesions. This suggests
      that prolactin could also be involved in the development of prostate cancer. In
      this study, we tested the hypothesis that elevated levels of circulating
      prolactin are associated with an increase in prostate cancer risk. We conducted a
      case-control study nested within the Northern Sweden Health and Disease Cohort
      using plasma samples collected from 29,560 men at a health survey. We measured
      prolactin in plasma from 144 men who had a diagnosis of prostate cancer after a
      median follow-up time of 4 years after health survey and from 289 controls
      matched for age and date of recruitment. Risk was not associated with plasma
      prolactin levels in univariate regression analysis. Odds ratios of prostate
      cancer for increasing quartiles of prolactin were 1.0, 0.92 (95% CI 0.51-1.65),
      0.82 (0.45-1.51) and 0.85 (0.49-1.47). Relative risk estimates remained unchanged
      after adjustments for height and weight or for plasma levels of testosterone, sex
      hormone-binding globulin, IGF-I and IGF-binding protein-3. Elevated circulating
      levels of prolactin were not related to an increase in prostate cancer risk,
      indicating that high circulating prolactin is not associated with development of
      prostate cancer.

PMID- 11291089
TI  - Non-human to human organ transplantation: its biologic basis and a potential role
      for radiation therapy.
AB  - There is an inadequate supply of human donor organs for transplantation.
      Xenotransplantation, the transplantation of organs from non-human animals to
      humans, is one of the potential solutions to this problem. The pig appears to be
      the preferred donor. For xenotransplantation to be successful, researchers must
      deal with three fundamental problems: (1) Hyperacute rejection of porcine organs,
      related to binding of xenoreactive natural antibodies of the recipient to
      antigens on the graft's endothelial cells, must be overcome. (2) Transmission of
      animal pathogens to humans must be prevented. Concern about zoonosis is not only
      directed to the transplant recipient but also concerns the risk that an
      infectious agent will be transferred from the recipient to the general
      population. (3) The xenografted organ must be physiologically compatible with the
      recipient. The physiological function of a pig organ in a human and its ability
      to sustain a human are problematic. Total lymphoid irradiation (TLI) and thoraco
      abdominal irradiation (TAI) as immunosuppressive modalities have been
      investigated in rodent-to-rodent, large mammals and non-human primates-to
      primates, and pig-to-primate models. In certain clinical situations, TLI and TAI
      may prove to be important components for the preparation of the xenotransplant
      recipient. Progress in genetic engineering and cloning may soon lead to clinical
      trials in xenotransplantation.

PMID- 11291091
TI  - Adjuvant radiotherapy following radical prostatectomy is more effective and less
      toxic than salvage radiotherapy for a rising prostate specific antigen.
AB  - Despite the trend toward earlier diagnosis of adenocarcinoma of the prostate,
      approximately 25% of men undergoing radical prostatectomy will have pathologic
      evidence of cancer extending outside of the prostate. These patients are at high
      risk for subsequent recurrence. Such relapses are almost always manifested
      initially as a rise in the Prostate Specific Antigen (PSA). Currently utilized
      PSA assays, however, will not detect a recurrence smaller than 10(7) to 10(8)
      cells, nor does PSA identify the site of recurrence. In contrast, the pathologic
      findings at the time of surgery can be used to reliably distinguish patients at
      risk for local recurrence from those more likely to fail distantly. Furthermore,
      adjuvant pelvic radiotherapy after prostatectomy, given to patients with an
      undetectable PSA who are at high risk for local recurrence, results in a higher
      disease free survival and fewer side effects than if radiotherapy is delayed
      until the PSA begins to rise. Thus, patients at high risk for local failure
      following radical prostatectomy, but at low risk for distant metastases (i.e.,
      those with positive surgical margins and an undetectable PSA) should be offered
      immediate adjuvant radiotherapy.

PMID- 11291092
TI  - Radiation therapy (RT) after prostatectomy: The case for salvage therapy as
      opposed to adjuvant therapy.
AB  - Patients with pathologic stage T3 or T4 prostate cancer who have undetectable PSA
      levels following radical retropubic prostatectomy (RRP) have a substantial risk
      of recurrence. Radiotherapy (RT) can be administered immediately following the
      RRP (immediate adjuvant RT) or may be postponed until the PSA level has risen to
      a level that is indicative of residual or recurrent prostate cancer (salvage RT).
      Immediate adjuvant RT can significantly reduce the risk of relapse, but does not
      appear to increase the rate of survival. Approximately two-thirds of patients
      with rising PSA levels after RRP can be salvaged with RT alone. This result was
      achieved in patients treated with an adequate dose of radiation before the PSA
      rose to > 1.1 ng/ml. While no one can be certain which approach (adjuvant or
      salvage RT) is better, future studies should examine this issue. Whether
      immediate postoperative adjuvant RT is of value to patients is the subject of two
      randomized prospective studies. The benefit of adjuvant RT is a matter of
      controversy. Salvage RT treats only those patients with proven residual prostate
      cancer. The salvage RT approach has several advantages. This approach spares
      approximately 40% of patients who have had an RRP for T3 or T4 prostate cancer
      and eliminates the risks and costs associated with adjuvant RT. Additionally, it
      appears that the results of immediate adjuvant RT are similar to those achieved
      with early salvage RT.

PMID- 11291093
TI  - Role of P-selectin in radiation-induced intestinal inflammatory damage.
AB  - The aims of our study were to characterize the dose- and time-dependent changes
      in endothelial P-selectin expression and the role of this adhesion molecule as a
      mediator of radiation-induced inflammation. For that purpose, endothelial P
      selectin expression was measured by the radiolabeled antibody technique in
      control and irradiated mice at 2, 6, and 24 hr following abdominal irradiation
      with 4 or 10 Gy; leukocyte endothelial cell interactions were assessed using
      intravital microscopy in intestinal venules following irradiation at the
      aforementioned doses and times in C57BL/6 and P-selectin-deficient mice. In wild
      type mice, radiation induced a time- and dose-dependent up-regulation of P
      selectin and a significant increase in the flux of rolling leukocytes 2 hr after
      irradiation. Irradiation induced a significant increase in leukocyte adhesion
      that was dose-dependent. Following irradiation, P-selectin-deficient mice did not
      show any increase in leukocyte rolling but did demonstrate a response in
      leukocyte adhesion similar to that of the wild-type mice. Radiation-induced dose
      dependent histological inflammatory damage that did not differ between P-selectin
      deficient and wild-type mice. We conclude that P-selectin is up-regulated
      following irradiation and is a key molecular determinant of leukocyte rolling but
      not leukocyte adhesion in this inflammatory condition. Therefore, isolated
      neutralization of this adhesion molecule is not an effective means for preventing
      radiation-induced inflammation.

PMID- 11291094
TI  - Loss of G2/M arrest correlates with radiosensitization in two human sarcoma cell
      lines with mutant p53.
AB  - We have examined the modulation of radiosensitivity by using caffeine in two
      human sarcoma cell lines both with a p53 mutation (US8-93 and LMS6-93). In both
      cell lines a strong irradiation-induced G2/M arrest was coupled with a low rate
      of apoptosis. Incubation with caffeine resulted in a low percentage of S and G2/M
      cells, associated with an accumulation in G1. With a higher caffeine
      concentration, we detected a lower clonogenic survival with IC(50) at 2 mM. In
      both cell lines incubation with caffeine completely prevents the irradiation
      induced G2/M arrest. This was connected to radiosensitization, but without direct
      correlation to an induction of apoptosis. The effect of radiosensitization rose
      with higher irradiation doses. However, in comparison with LMS6-93, it was
      stronger in cell line US8-93. A higher radiosensitization in US8-93 correlated
      with the prevention of strong irradiation-induced G2/M response and higher
      initial DNA damage. Results of Western hybridization reveal a p53-independent
      mechanism of radiosensitization caused by caffeine. Our findings suggest that
      modulation in G2/M regulation may affect a common checkpoint for tumor cells with
      defective p53 function. Furthermore, our results show that the enhancer effect of
      caffeine is dependent on a strong reduction in the number of G2/M arrested cells
      and on an inhibition of DNA damage repair after irradiation.

PMID- 11291095
TI  - IUdR polymers for combined continuous low-dose rate and high-dose rate
      sensitization of experimental human malignant gliomas.
AB  - Local polymeric delivery enhances IUdR radiosensitization of human malignant
      gliomas (MG). The combined low-dose rate (LDR) (0.03 Gy/h) and fractionated high
      dose rate (HDR) treatments result in cures of experimental MGs. To enhance
      efficacy, we combined polymeric IUdR delivery, LDR, and HDR for treatments of
      both subcutaneous and intracranial MGs. In vitro: Cells (U251 MG) were
      trypsinized and replated in triplicate 1 day prior to LDR irradiation in media
      either without (control) or with 10 microM IUdR. After 72 hr, LDR irradiation
      cells were acutely irradiated (1.1 Gy/min) with increasing (0, 1.25, 2.5, 5.0, or
      10 Gy) single doses. Implantable IUdR polymers [(poly(bis(p-carboxyphenoxy)
      propane) (PCPP): sebaic acid (PCPP:SA), 20:80] (50% loading; 10 mg) were
      synthesized. In vivo: For flank vs. intracranial tumors, mice had 6 x 10(6)
      subcutaneous vs. 2 x 10(5) intracranial cells. For intracranial or subcutaneous
      MGs, mice had intratumoral blank (empty) vs. IUdR polymer treatments. One day
      after implantation, mice had immediate external LDR (3 cGy/h x 3 days total body
      irradiation) or HDR (2 Gy BID x 4 days to tumor site) or concurrent treatments.
      For the in vitro IUdR treatments, LDR resulted in a striking increase in cell
      killing when combined with HDR. For the in vivo LDR treatments of flank tumors,
      the growth delay was greater for the IUdR vs. blank polymer treatments. For the
      combined LDR and HDR, the IUdR treatments resulted in a dramatic decrease in
      tumor volumes. On day 60 the log V/V0 were -1.7 +/- 0.22 for combined LDR + HDR +
      IUdR polymer (P < 0.05 vs. combined LDR + HDR + blank polymer). Survival for the
      intracranial controls was 22.9 +/- 1.2 days. For the blank polymer + LDR vs.
      blank polymer + LDR + HDR treatments, survival was 25.3 +/- 1.7 (P = NS) vs. 48.1
      +/- 3.5 days (P < 0.05). For IUdR polymer + LDR treatment survival was 27.3 +/-
      2.3 days (P = NS). The most striking improvement in survival followed the IUdR
      polymer + LDR + HDR treatment: 66.0 + 6.4 days (P < 0.05 vs. blank polymer + LDR
      + HDR). The polymeric IUdR delivery plus combined continuous LDR and HDR
      treatments results in growth delay and improved survival in animals bearing the
      MG xenografts. This treatment may hold promise for the treatment of human MGs.

PMID- 11291096
TI  - Comparison of intensity modulated radiation therapy (IMRT) treatment techniques
      for nasopharyngeal carcinoma.
AB  - We studied target volume coverage and normal tissue sparing of serial tomotherapy
      intensity modulated radiation therapy (IMRT) and fixed-field IMRT for
      nasopharyngeal carcinoma (NPC), as compared with those of conventional beam
      arrangements. Twelve patients with NPC (T2-4N1-3M0) at Mallinckrodt Institute of
      Radiology underwent computed tomography simulation. Images were then transferred
      to a virtual simulation workstation computer for target contouring. Target gross
      tumor volumes (GTV) were primary nasopharyngeal tumor (GTV(NP)) with a
      prescription of 70 Gy, grossly enlarged cervical nodes (GTV(LN)) with a
      prescription of 70 Gy, and the uninvolved cervical lymphatics [designated as the
      clinical tumor volume (CTV)] with a prescription of 60 Gy. Critical organs,
      including the parotid gland, spinal cord, brain stem, mandible, and pituitary
      gland, were also delineated. Conventional beam arrangements were designed
      following the guidelines of Intergroup (SWOG, RTOG, ECOG) NPC Study 0099 in which
      the dose was prescribed to the central axis and the target volumes were aimed to
      receive the prescribed dose +/- 10%. Similar dosimetric criteria were used to
      assess the target volume coverage capability of IMRT. Serial tomotherapy IMRT was
      planned using a 0.86-cm wide multivane collimator, while a dynamic multileaf
      collimator system with five equally spaced fixed gantry angles was designated for
      fixed-beam IMRT. The fractional volume of each critical organ that received a
      certain predefined threshold dose was obtained from dose-volume histograms of
      each organ in either the three-dimensional or IMRT treatment planning computer
      systems. Statistical analysis (paired t-test) was used to examine statistical
      significance. We found that serial tomotherapy achieved similar target volume
      coverage as conventional techniques (97.8 +/- 2.3% vs. 98.9 +/- 1.3%). The static
      field IMRT technique (five equally spaced fields) was inferior, with 92.1 +/-
      8.6% fractional GTV(NP) receiving 70 Gy +/- 10% dose (P < 0.05). However, GTV(LN)
      coverage of 70 Gy was significantly better with both IMRT techniques (96.1 +/-
      3.2%, 87.7 +/- 10.6%, and 42.2 +/- 21% for tomotherapy, fixed-field IMRT, and
      conventional therapy, respectively). CTV coverage of 60 Gy was also significantly
      better with the IMRT techniques. Parotid gland sparing was quantified by
      evaluating the fractional volume of parotid gland receiving more than 30 Gy; 66.6
      +/- 15%, 48.3 +/- 4%, and 93 +/- 10% of the parotid volume received more than 30
      Gy using tomotherapy, fixed-field IMRT, and conventional therapy, respectively (P
      < 0.05). Fixed-field IMRT technique had the best parotid-sparing effect despite
      less desirable target coverage. The pituitary gland, mandible, spinal cord, and
      brain stem were also better spared by both IMRT techniques. These encouraging
      dosimetric results substantiate the theoretical advantage of inverse-planning
      IMRT in the management of NPC. We showed that target coverage of the primary
      tumor was maintained and nodal coverage was improved, as compared with
      conventional beam arrangements. The ability of IMRT to spare the parotid glands
      is exciting, and a prospective clinical study is currently underway at our
      institution to address the optimal parotid dose-volume needs to be spared to
      prevent xerostomia and to improve the quality of life in patients with NPC.

PMID- 11291097
TI  - Gemcitabine following radiotherapy with concurrent 5-fluorouracil for
      nonmetastatic adenocarcinoma of the pancreas.
AB  - Gemcitabine has been shown to be an active agent in the treatment of pancreatic
      cancer. This study was conducted to prospectively examine the tolerance and early
      efficacy of adjuvant gemcitabine following radiotherapy with concurrent 5
      fluorouracil (5-FU) for nonmetastatic pancreatic adenocarcinoma. Twenty-three
      patients, median age 64 years, were treated with combined modality therapy. Nine
      patients underwent tumor resection before chemoradiation; 14 patients with
      locally unresectable tumors received definitive chemoradiation. Radiotherapy
      utilized four fields to the tumor and lymphatics to 45 Gy, plus a lateral boost
      to 50.4 Gy. Concurrent 5-FU 500 mg/m(2)/day was administered on days 1-3 and 29
      31, followed by 4 months of gemcitabine 1,000 mg/m(2)/week for 3 weeks (fourth
      week break). Adjuvant gemcitabine was well tolerated. Eighty-three percent of the
      patients completed three to four cycles. The primary dose-limiting toxicity was
      leukopenia, which was observed in 10 patients (43%). Nonhematologic toxicities
      were reported in five patients (22%). There were no cases of gemcitabine-induced
      radiation recall and there have been no deaths attributed to treatment toxicity.
      Median follow-up for the 23 patients was 12 months (range, 5-50); the actuarial
      median survival was 13 months. This report confirms that adjuvant gemcitabine
      following radiotherapy with concurrent 5-FU for nonmetastatic pancreatic
      adenocarcinoma can be safely administered.

PMID- 11291098
TI  - An investigation of a model of percentage depth dose for irregularly shaped
      fields.
AB  - A significant component of the total dose delivered to tumor and surrounding
      tissue during a radiation treatment arises from the scattering of the primary
      beam. Accounting for this component accurately and efficiently is a necessity. In
      this study we investigate a method for calculating the phantom-scatter
      contributions to the total dose by simple summation of scatter dose from a set of
      individual triangles that span an irregular field. The calculation of phantom
      scatter is based on a two-parameter model, which is applicable to regions where
      electron equilibrium is established. The two physical parameters are the dose
      averaged linear attenuation coefficient and the beam-hardening coefficient. The
      advantage of this model is that it is a natural method when an irregular field is
      shaped by a multi-leaf collimator (MLC). Accuracy is not compromised by the
      triangulation since the irregular field is defined by the straight edges of the
      MLC leaves. The model predicts the percent depth dose with acceptable accuracy
      for any arbitrary shape of fields. We report on results for 6- and 18-MV photon
      beams and for a number of irregularly shaped fields.

PMID- 11291099
TI  - Conditional modification of behavior in Drosophila by targeted expression of a
      temperature-sensitive shibire allele in defined neurons.
AB  - Behavior is a manifestation of temporally and spatially defined neuronal
      activities. To understand how behavior is controlled by the nervous system, it is
      important to identify the neuronal substrates responsible for these activities,
      and to elucidate how they are integrated into a functional circuit. I introduce a
      novel and general method to conditionally perturb anatomically defined neurons in
      intact Drosophila. In this method, a temperature-sensitive allele of shibire
      (shi(ts1)) is overexpressed in neuronal subsets using the GAL4/UAS system.
      Because the shi gene product is essential for synaptic vesicle recycling, and
      shi(ts1) is semidominant, a simple temperature shift should lead to fast and
      reversible effects on synaptic transmission of shi(ts1) expressing neurons. When
      shi(ts1) expression was directed to cholinergic neurons, adult flies showed a
      dramatic response to the restrictive temperature, becoming motionless within 2
      min at 30 degrees C. This temperature-induced paralysis was reversible. After
      being shifted back to the permissive temperature, they readily regained their
      activity and started to walk in 1 min. When shi(ts1) was expressed in
      photoreceptor cells, adults and larvae exhibited temperature-dependent blindness.
      These observations show that the GAL4/UAS system can be used to express shi(ts1)
      in a specific subset of neurons to cause temperature-dependent changes in
      behavior. Because this method allows perturbation of the neuronal activities
      rapidly and reversibly in a spatially and temporally restricted manner, it will
      be useful to study the functional significance of particular neuronal subsets in
      the behavior of intact animals.

PMID- 11291100
TI  - Activin type II receptors in embryonic dorsal root ganglion neurons of the
      chicken.
AB  - Activin induces neuropeptide expression in chicken ciliary ganglion neurons. To
      determine if activin might also influence neuropeptide expression in developing
      sensory neurons, we examined whether type II activin receptors are expressed
      during embryonic development of the chicken dorsal root ganglia (DRG), and also
      examined the effects of activin on neuropeptide expression in cultured DRG
      neurons. Using reverse transcription polymerase chain reaction (rtPCR), we
      detected mRNAs for both the activin receptors type IIA (ActRIIA) and type IIB
      (ActRIIB) in DRG from embryonic day 7 through posthatch day 1. With in situ
      hybridization, we found that morphologically identifiable neurons express mRNAs
      for both ActRIIA and ActRIIB. With developmental age, a subset of neurons that
      hybridizes more intensely with riboprobes to these receptor mRNAs becomes
      evident. A similar pattern of expression is observed with immunocytochemical
      staining using antisera against activin type II receptors. To examine whether
      embryonic DRG cells respond to activin we treated dissociated cultures of DRG
      with activin A and assessed the expression of vasoactive intestinal peptide (VIP)
      and calcitonin gene related peptide (CGRP) mRNAs using semiquantitative rtPCR.
      Activin treatment results in an increase in VIP mRNA, but does not affect CGRP
      mRNA levels. These observations indicate that neurons in the embryonic chicken
      DRG can respond to activin and suggest that activin has the potential to play a
      role in the development and function of DRG sensory neurons.

PMID- 11291101
TI  - Behavioral discrimination of sexually dimorphic calls by male zebra finches
      requires an intact vocal motor pathway.
AB  - Vocal communication between zebra finches includes the exchange of long calls
      (LCs) as well as song. By using this natural call behavior and quantifying the
      LCs emitted in response to playbacks of LCs of other birds, we have previously
      shown that adult male zebra finches have a categorical preference for the LCs of
      females over those of males. Female LCs are acoustically simpler than male LCs,
      which include complex acoustic features that are learned during development.
      Production of these male-typical features requires an intact nucleus RA, the
      sexually dimorphic source of the main telencephalic projection to brainstem vocal
      effectors. We have now made bilateral lesions of RA in 17 adult males and tested
      their discrimination behavior in the call response situation. Lesioned birds
      continue to call, but lose the male-typical preference for female LCs. The degree
      of loss is correlated with the extent of RA damage. Further, the simplified LCs
      of males with RA lesions have a variable duration that is correlated with
      stimulus features. In effect, the call response behavior of lesioned males
      becomes like that of females. Apparently, in the absence of RA, the remaining
      intact structures receive different call information than RA normally does,
      and/or process it differently. This suggests that the vocal motor nucleus RA
      could play a role in the transformation of a signal encoding the salience of
      stimulus parameters into a control signal that modulates the probability and
      strength of responding.

PMID- 11291102
TI  - New reproductive anomalies in fruitless-mutant Drosophila males: extreme
      lengthening of mating durations and infertility correlated with defective
      serotonergic innervation of reproductive organs.
AB  - Several features of male reproductive behavior are under the neural control of
      fruitless (fru) in Drosophila melanogaster. This gene is known to influence
      courtship steps prior to mating, due to the absence of attempted copulation in
      the behavioral repertoire of most types of fru-mutant males. However, certain
      combinations of fru mutations allow for fertility. By analyzing such matings and
      their consequences, we uncovered two striking defects: mating times up to four
      times the normal average duration of copulation; and frequent infertility,
      regardless of the time of mating by a given transheterozygous fru-mutant male.
      The lengthened copulation times may be connected with fru-induced defects in the
      formation of a male-specific abdominal muscle. Production of sperm and certain
      seminal fluid proteins are normal in these fru mutants. However, analysis of
      postmating qualities of females that copulated with transheterozygous mutants
      strongly implied defects in the ability of these males to transfer sperm and
      seminal fluids. Such abnormalities may be associated with certain serotonergic
      neurons in the abdominal ganglion in which production of 5HT is regulated by fru.
      These cells send processes to contractile muscles of the male's internal sex
      organs; such projection patterns are aberrant in the semifertile fru mutants.
      Therefore, the reproductive functions regulated by fruitless are expanded in
      their scope, encompassing not only the earliest stages of courtship behavior
      along with almost all subsequent steps in the behavioral sequence, but also more
      than one component of the culminating events.

PMID- 11291103
TI  - Postnatal cell proliferation and death in a lateralized, gender-related,
      asymmetric nucleus.
AB  - Sexual differentiation and lateralization of neurone number in a discrete
      forebrain nucleus (SDApc) related to masculine vocal emission, occur
      contemporaneously in postnatal (P0-P15) gerbils. Stereological estimates of cell
      proliferation and death during SDApc organization were made by BrdU labelling and
      pyknosis, respectively. Results confirmed that rates of apoptosis were greater in
      females and lateralized in males. Immunoreactive BrdU cells, located in the SDApc
      at P0-P6, with low levels at P15, were not numerically different between the
      sexes. Only at one age, P0, in males, was a left-right difference seen in BrdU
      immunoreactive cell numbers. Microglia, identified by isolectin immunostaining,
      were numerically similar to BrdU cells. We suggest that apoptosis, rather than
      neurogenesis, differentiates and lateralizes SDApc organization, and
      proliferating cells are microglia, phagocytosing debris.

PMID- 11291105
TI  - Increases of IgA milk concentrations correlate with IgA2 increment.
AB  - IgA, IgA1, and IgA2 concentrations were determined in 81 defatted human milk
      samples: colostrum (days 1-5, n = 42), transitional milk (days 6-14, n = 18) and
      mature milk (days 15-75, n = 21) by immunonephelometry. Correlations were found
      between total IgA levels and the concentrations of both IgA subclasses (P <
      0.0001). The levels of the three molecules decreased over lactation with
      significant differences (P < 0.05) between colostrum and transitional milk levels
      and between colostrum and mature milk. Colostral IgA1 and IgA2 mean
      concentrations dropped respectively from 10.89 +/- 2.12 g/L, and 15.41 +/- 2.10
      g/L to 1.83 +/- 0.73 g/L and 3.40 +/- 1.25 g/L in transitional milk reaching
      finally to 0.36 +/- 0.07 g/L and 0.27 +/- 0.06 g/L in mature milk. IgA2
      concentrations were higher than those of IgA1 when the total IgA level was high.
      The IgA2 levels in colostrum could be an adaptation resistance of IgA to
      potentially harmful pathogens able to secrete IgA proteases and also a way to
      regulate colonization of the microflora in the newborn.

PMID- 11291106
TI  - Plasma and urinary endothelin-1 in focal segmental glomerulosclerosis.
AB  - The kidney is an important site of endothelin-1 (ET-1) production and is
      particularly susceptible to ET-1 action. Infusion of ET-1 in rats induces both
      functional and morphological alterations in the kidneys. Increased plasma level
      of ET-1 has been reported in patients with chronic renal failure. However, there
      are still no reports on the plasma and urinary ET-1 levels in patients with focal
      segmental glomerulosclerosis (FSGS). In the present study, we have measured the
      plasma concentration and urinary excretion rate of ET-1 in 15 patients with
      nephrotic syndrome due to FSGS, and observed the serial changes of plasma and
      urinary ET-1 in nephrotic rats with FSGS, induced by repeated injection with
      puromycin aminonucleoside (PAN). ET-1 was measured with radioimmunoassay. The
      results showed that plasma ET-1 concentration in FSGS patients was significantly
      higher than in normal controls (P < 0.05), and that urinary ET-1 excretion rate
      was also significantly higher in FSGS patients than in normal controls (P <
      0.01). In FSGS patients, the plasma and urinary ET-1 was significantly correlated
      (P < 0.05), and the urinary ET-1 excretion rate was significantly correlated with
      the amount of proteinuria (P < 0.05) and the glomerular sclerosing score (P <
      0.01). In the ten rats with PAN-induced FSGS, serial examination showed a
      significant increase in plasma ET-1 after 8 weeks of injections, while the
      urinary ET-1 excretion rate showed a biphasic increase that showed a peak after 4
      to 6 weeks. The same changes in plasma and urinary ET-1 levels were not observed
      in control rats injected with normal saline at the same frequency. Our results
      suggest that ET-1 may be involved in the pathogenesis of FSGS in both humans and
      rats.

PMID- 11291108
TI  - Histamine release test and measurement of antigen-specific IgE antibody in the
      diagnosis of allergic conjunctival diseases.
AB  - Although systemic allergic laboratory tests for the quantification of allergen
      specific serum IgE antibody have been widely used, in these tests a high titer of
      serum specific IgE does not necessarily indicate evidence of allergy. We
      evaluated the diagnostic value of the glass microfiber-based histamine release
      test (HRT) using small amounts of whole blood, in 36 cases of allergic
      conjunctival diseases: 17 cases of allergic conjunctivitis and 19 of atopic
      keratoconjunctivitis. The patients were evaluated by HRT, capsulated hydrolic
      carrier polymer (CAP)-RAST, and conjunctival provocation test (CPT) against ten
      allergens. The positive rates for all allergens were higher in CAP-RAST than in
      HRT. The mean concordance of HRT with CAP-RAST results was 0.789. The mean
      concordance of HRT with CPT was 0.892 and that of CAP-RAST with CPT was 0.693. A
      significantly higher concordance was observed in HRT than CAP-RAST for Japanese
      cedar and mite antigen. The mean sensitivity, specificity, and efficiency of HRT
      were higher than those of CAP-RAST. These results indicate that CAP-RAST is good
      for the screening of allergens and that HRT has an advantage in the confirmation
      of clinical allergens in allergic conjunctival diseases because of its high
      sensitivity, specificity, efficiency, and higher concordance with CPT.

PMID- 11291107
TI  - Effect of substrate size on immunoinhibition of amylase activity.
AB  - Immunoinhibition assays are hypothesized to work by antibodies blocking substrate
      access to enzyme active sites. To test this hypothesis, the inhibition of amylase
      isoenzymes by monoclonal and polyclonal antisera was assessed using substrates of
      varying sizes: chromogenic sustrates 3, 5, or 7 glucose units in length, novel
      synthetic macromolecular substrates, and starch. The synthetic macromolecular
      substrates consisted of small oligosaccharide substrates linked to an inert
      polymer that conferred a large size to substrate molecules as determined by gel
      filtration chromatography. When substrate size increased, amylase activity could
      be inhibited equivalently by antibody concentrations that are 10-fold lower.
      Progressively less polyclonal serum was required to inhibit amylase activity as
      substrate length increased from 3 to 5 to 7 glucose units and as size was
      increased by linkage to a polymer. Different effects of substrate size were
      observed with two monoclonal antibodies. One monoclonal antibody blocked amylase
      activity independent of substrate size, while another monoclonal antibody had
      little inhibitory effect except using starch as substrate. We conclude that use
      of larger substrates can expand the repertoire of inhibitory epitopes on enzymes
      and convert a noninhibitory antibody into an inhibitory one.

PMID- 11291109
TI  - Negative interference of bilirubin and hemoglobin in the MEIA troponin I assay
      but not in the MEIA CK-MB assay.
AB  - Troponin I is a sensitive and specific marker for the diagnosis of myocardial
      infarction. Several commercially available immunoassays measure the concentration
      of troponin I in serum. The microparticle enzyme immunoassay (MEIA) for troponin
      I (Abbott Laboratories, Abbott Park, IL) is widely used in clinical laboratories,
      including our hospital laboratory. We studied the effect of bilirubin and
      hemolysis on the MEIA for troponin I and compared our assay with a newly
      available chemiluminescent assay (CLIA) for troponin I (Bayer Diagnostics,
      Tarrytown, NY). We also measured CK-MB concentration using the MEIA CK-MB assay.
      One serum pool was prepared by combining several specimens of one patient with
      elevated troponin I and with a diagnosis of myocardial infarction. Other serum
      pools were prepared by combining sera with similar troponin I values. All serum
      pools showed normal bilirubin concentrations and had no hemolysis. Then we
      supplemented aliquots of serum pools with various concentrations of bilirubin
      (5.0, 10.0, 15.0, and 20.0 mg/dL). After supplementation, troponin I
      concentrations were measured again using the MEIA and CLIA. We observed a
      statistically significant decrease in troponin I concentration in the presence of
      bilirubin with the MEIA. For example, in serum pool 1, the troponin I
      concentration was 16.3 (bilirubin: 0.8 mg/dL). In the presence of 5.0, 10.0, 15.0
      and 20.0 mg/dL of added bilirubin, the cardiac troponin I concentrations were
      13.9, 13.4, 13.3 and 13.0 ng/ml respectively. We observed similar negative
      interference of bilirubin in troponin I measurement by the MEIA in other pools.
      The troponin I value decreased slightly (not statistically significant) in one
      pool and did not change in two other pools in the presence of bilirubin when we
      measured troponin I concentration using the CLIA. Interestingly, bilirubin did
      not interfere with the MEIA CK-MB assay. Moderate hemolysis did not have any
      effect on the troponin I assay using either the MEIA or CLIA. However, gross
      hemolysis (hemoglobin > 40 mg/dL) interfered with both assays for troponin I.

PMID- 11291110
TI  - Differential distribution of soluble and complexed forms of prostate-specific
      antigen in cyst fluids of women with gross cystic breast disease.
AB  - Gross cystic breast disease (GCBD) is the most common benign disease of the human
      female breast, and patients with GCBD have an increased risk of breast cancer.
      The aim of this study was to evaluate the distribution inside apocrine cells and
      in breast cyst fluids aspirated from gross cysts of prostate-specific antigen
      (PSA) molecular forms, and to correlate the different intracystic PSA profiles to
      the subpopulations of gross cysts. Type I cysts showed a median value of 0.71
      microg/L of total PSA and 0.32 g/L of ACT, significantly different to that of
      Type II cysts (Wilcoxon P < 0.001). Although large excesses of ACT were detected
      in all samples, BCF samples and apocrine cells from Type I gross cysts contained
      about 70% of free PSA, compared to the higher amounts of complexed PSA found in
      Type II gross cysts. We demonstrate that in apocrine/secretive Type I breast
      gross cysts the serine protease PSA was mainly present in its free form, in
      contrast to a major proportion of complexed PSA found in flattened/transudative
      Type II cysts. Our results are consistent with the notion that a prolonged
      exposure of apocrine breast cells lining the Type I gross cysts to the
      proteolytic activity of PSA could be involved in the etiopathogenesis of GCBD.

PMID- 11291111
TI  - Molecular detection and identification of an enterovirus during an outbreak of
      aseptic meningitis.
AB  - Stool samples from sixteen cases of children with meningitis originating from
      four different and geographically isolated parts of Greece were investigated for
      enteroviruses. The conventional method of cell culture in four different cell
      lines was initially used for the isolation of enteroviruses. The results showed a
      cytopathic effect (CPE) in all cases after two, or even more successive passages
      in only one cell line (RD), although a less-than-satisfactory CPE was obtained in
      many cases. Seroneutralization with RIVM mixed hyperimmune antisera followed and
      the isolates were typed as Coxsackie B viruses. The method of RT-PCR with
      enterovirus-specific primers targeted to the highly conserved 5'-UTR of the
      genome was initially used for the detection of enteroviruses from the inoculated
      cell cultures. A positive RT-PCR result was obtained for all of the clinical
      samples rapidly and accurately and the isolates were further characterized with
      the aid of Restriction Fragment Length Polymorphism (RFLP) analysis and Single
      Strand Conformation Polymorphism analysis (SSCP) of the amplicons. The RFLP
      analysis showed first of all that the isolates had an identical restriction
      pattern with Coxsackie B5 Faulkner reference strain with 4 out of 5 restriction
      enzymes and secondly, both RFLP and SSCP analysis indicated the epidemiological
      association of the isolates. The speed of the molecular methodology that was used
      in comparison with the conventional methods and its possible significance for the
      description of virus evolution and circulation in the populations is discussed.

PMID- 11291112
TI  - Ganglioside agglutination immunoassay for rapid detection of autoantibodies in
      immune-mediated neuropathy.
AB  - Elevated levels of serum autoantibodies directed against gangliosides are closely
      associated with acute and chronic autoimmune neuropathies. An agglutination
      immunoassay using polystyrene microparticles coated with a total extract of brain
      gangliosides was used to test patient sera for the presence of anti-ganglioside
      antibodies. Results were compared with those obtained by ELISA for anti-GM1 and
      anti-GQ1b ganglioside antibodies. Eight of the twelve sera from patients with
      multifocal motor neuropathy and seven of the thirteen sera from patients with
      Guillain-Barre syndrome were positive for the presence of anti-ganglioside
      antibodies by the ganglioside agglutination immunoassay. The assay compared
      favorably with the ELISA system in sensitivity and specificity, while requiring a
      fraction of the time and cost to perform. The new assay can serve as a rapid and
      effective method for detecting or screening for anti-ganglioside antibodies in
      patients with acute or chronic immune-mediated neuropathies. It would be
      particularly useful for detecting antibodies that react with multiple
      gangliosides, or with minor or as yet uncharacterized gangliosides.

PMID- 11291113
TI  - Identification of human enterovirulent Escherichia coli strains by multiplex PCR.
AB  - Some strains of Escherichia coli are involved in enteric infections in both
      adults and children. However the classical diagnostic methods can not
      differentiate pathogenic from nonpathogenic E. coli, because of the lack of
      phenotypic differences. In this study, we developed multiplex PCR in order to
      amplify fragments of specific virulence genes of the five main E. coli
      pathotypes. Fragments of the expected size were obtained using previously or
      newly designed primers and allowed identification of 10 virulence genes in only 5
      reactions. This method was applied to the detection of pathogenic E. coli
      isolated from 90 patients' stools specimens during an 18-month survey. Patients
      were suffering from diarrhea or hemolytic uremic syndrome and in 13 cases
      (14.4%), an enterovirulent E. coli strain was detected. This diagnostic method
      could therefore represent an important technique in clinical laboratories which
      lack standard tests for these pathogens.

PMID- 11291114
TI  - The potential of inductively coupled plasma mass spectrometry detection for high
      performance liquid chromatography combined with accurate mass measurement of
      organic pharmaceutical compounds.
AB  - Quantification of unknown components in pharmaceutical, metabolic and
      environmental samples is an important but difficult task. Most commonly used
      detectors (like UV, RI or MS) require standards of each analyte for accurate
      quantification. Even if the chemical structure or elemental composition is known,
      the response from these detectors is difficult to predict with any accuracy. In
      inductively coupled plasma mass spectrometry (ICP-MS) compounds are atomised and
      ionised irrespective of the chemical structure(s) incorporating the element of
      interest. Liquid chromatography coupled with inductively coupled plasma mass
      spectrometry (LC/ICP-MS) has been shown to provide a generic detection for
      structurally non-correlated compounds with common elements like phosphorus and
      iodine. Detection of selected elements gives a better quantification of tested
      'unknowns' than UV and organic mass spectrometric detection. It was shown that
      the ultrasonic nebuliser did not introduce any measurable dead volume and
      preserves the separation efficiency of the system. ICP-MS can be used in
      combination with many different mobile phases ranging from 0-100% organic
      modifier. The dynamic range was found to exceed 2.5 orders of magnitude. The
      application of LC/ICP-MS to pharmaceutical drugs and formulations has shown that
      impurities can be quantified below the 0.1 mol-% level.

PMID- 11291116
TI  - Development of a method based on accelerated solvent extraction and liquid
      chromatography/mass spectrometry for determination of arylphenoxypropionic
      herbicides in soil.
AB  - A sensitive and specific analytical procedure for determining
      arylphenoxypropionic herbicides in soil samples, using Ionspray ionization (ISI)
      liquid chromatography/mass spectrometry (LC/MS), is presented.
      Arylphenoxypropionic acids are a new class of herbicides used for selective
      removal of most grass species from any non-grass crop, commercialized as
      herbicide esters. Previous studies have shown that the esters undergo fast
      hydrolysis in the presence of vegetable tissues and soil bacteria, yelding the
      corresponding free acid. The feasibility of rapidly extracting
      arylphenoxypropionic herbicides from soil by accelerated solvent extraction (ASE)
      techniques was evaluated. Four different soil samples were fortified with target
      compounds at levels of 5 and 20 ng/g by following a procedure able to mimic
      weathered soils. Herbicides were extracted by a methanol/water (80:20 v/v)
      solution (0.12 M) of NaCl at 90 degrees C. After clean-up using graphitized
      carbon black (GCB) as absorbent, the extract was analyzed by HPLC/ISI-MS. The
      effect of concentration of acid in the mobile phase on the response of ISI-MS was
      investigated. The effects of varying the orifice plate voltage on the production
      of diagnostic fragment ions, and on the response of the MS detector, were also
      investigated. The ISI-MS response was linearly related to the amounts of analytes
      injected between 1 and 200 ng. The limit of detection (signal-to-noise ratio = 3)
      of the method for the pesticides in soil samples was estimated to be less than 1
      ng/g.

PMID- 11291117
TI  - A cylindrical capacitor ionization source: droplet generation and controlled
      charge reduction for mass spectrometry.
AB  - A cylindrical capacitor ionization source was used in conjunction with corona
      discharge charge reduction for generation of singly charged ions for mass
      spectrometric analysis. The source consists of a fused-silica capillary threaded
      with a platinum wire and placed inside a stainless steel tube. Application of an
      electric potential to the wire results in the production of a linear stream of
      charged droplets when an aqueous solution is pumped through the capillary.
      Subsequent solvent evaporation yields ions, providing a continuous ion source for
      mass spectrometry. Passage of the ions through a corona discharge charge
      reduction chamber permits reduction of the charge state to predominantly singly
      charged species, facilitating analysis of DNA and protein mixtures. The change
      from production of multiply charged ions to production of singly charged ions is
      extremely simple, requiring only modulation of the voltage applied to the corona
      discharge electrode. A simple technique for construction of the ionization source
      is reported.

PMID- 11291118
TI  - Rapid bioanalysis of vancomycin in serum and urine by high-performance liquid
      chromatography tandem mass spectrometry using on-line sample extraction and
      parallel analytical columns.
AB  - A novel high-performance liquid chromatography tandem mass spectrometry
      (LC/MS/MS) method is described for the determination of vancomycin in serum and
      urine. After the addition of internal standard (teicoplanin), serum and urine
      samples were directly injected onto an HPLC system consisting of an extraction
      column and dual analytical columns. The columns are plumbed through two switching
      valves. A six-port valve directs extraction column effluent either to waste or to
      an analytical column. A ten-port valve simultaneously permits equilibration of
      one analytical column while the other is used for sample analysis. Thus, off-line
      analytical column equilibration time does not require mass spectrometer time,
      freeing the detector for increased sample throughput. The on-line sample
      extraction step takes 15 seconds followed by gradient chromatography taking
      another 90 seconds. Having minimal sample pretreatment the method is both simple
      and fast. This system has been used to successfully develop a validated positive
      ion electrospray bioanalytical method for the quantitation of vancomycin.
      Detection of vancomycin was accurate and precise, with a limit of detection of 1
      ng/mL in serum and urine. The calibration curves for vancomycin in rat, dog and
      primate were linear in a concentration range of 0.001-10 microg/mL for serum and
      urine. This method has been successfully applied to determine the concentration
      of vancomycin in rat, dog and primate serum and urine samples from
      pharmacokinetic and urinary excretion studies.

PMID- 11291119
TI  - Alcohol in breath and blood: a selected ion flow tube mass spectrometric study.
AB  - In this paper we compare the amounts of ethanol in breath and in blood after
      ingestion of whisky using analysis by selected ion flow tube mass spectrometry
      (SIFT-MS). Blood ethanol concentrations were also obtained using standard
      hospital forensic procedures for blood alcohol analyses. We demonstrate the
      quantitative nature of SIFT-MS analysis by correlating the observed alcohol
      content of the headspace above 5-mL amounts of venous blood and aqueous solution
      to which known trace amounts of alcohol have been added. This procedure provides
      a Henry's Law coefficient for ethanol in aqueous solution at 298 +/- 3 K of 209
      +/- 7 mol/kg*bar. We also demonstrate that measurement of the ethanol
      concentration in the alveolar portion of a single breath using the SIFT-MS
      technique gives an accurate measure of blood alcohol and could obviate the need
      for blood samples in forensic processing. The storage performance of breath
      samples in Mylar bags with a volume greater than 1 L has been shown to maintain
      the mixture integrity for ethanol but not for some other species.

PMID- 11291120
TI  - Principal component analysis of mass spectra of peptides generated from the
      tryptic digestion of protein mixtures.
AB  - Principal component analysis (PCA) has been used to analyse mass spectral peptide
      profiles obtained from the enzymatic digestion of standard protein mixtures.
      Scores and loadings plots clearly revealed peptide fragments that differentiated
      one protein mixture from another. Peptide map search results identified with a
      high degree of certainty any additional proteins in these mixtures. As a proof-of
      concept this methodology was applied to hepatic protein mixtures obtained from
      rats treated with two hepatotoxic compounds: methapyriline and SB-219994. Liver
      proteins were extracted, pre-separated by one-dimensional polyacrylamide gel
      electrophoresis, subjected to tryptic digestion and analysed by mass
      spectrometry. Two up-regulated proteins, glutathione S-transferase with
      methapyrilene and peroxisomal bifunctional enzyme with SB-219994, were identified
      in this manner.

PMID- 11291121
TI  - Identification of proteins from Escherichia coli using two-dimensional semi
      preparative electrophoresis and mass spectrometry.
AB  - Escherichia coli is a gram-negative bacterium that causes sepsis and infections
      of the nervous system, and the digestive and urinary tracts. The availability of
      the complete nucleotide sequence encoding the E. coli K-12 genome has made this
      organism an excellent model for proteomic studies. Semi-preparative two
      dimensional electrophoresis, including liquid phase isoelectric focusing (IEF),
      one-dimensional sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis
      (PAGE) and gel elution, have for the first time been used in combination with
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOFMS), electrospray tandem mass spectrometry and database searching for
      rapid separation of proteins from a uropathogenic strain of E. coli. The identity
      of 30 proteins, including the membrane protein nmpC, was obtained using this
      approach.

PMID- 11291123
TI  - Identification of barley and rye varieties using matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry with neural networks.
AB  - Cereal varieties are normally identified using time-consuming methods such as
      visual examination of either the intact grain or one-dimensional electrophoretic
      patterns of the grain storage proteins. A fast method for identification of wheat
      (Triticum aestivum L.) varieties has previously been developed, which combines
      analysis of alcohol-soluble wheat proteins (gliadins) using matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry with neural networks. Here
      we have applied the same method for the identification of both barley (Hordeum
      vulgare L.) and rye (Secale cereale L.) varieties. For barley, 95% of the mass
      spectra were correctly classified. This is an encouraging result, since in
      earlier experiments only a grouping into subsets of varieties was possible.
      However, the method was not useful in the classification of rye, due to the
      strong similarity between mass spectra of different varieties.

PMID- 11291125
TI  - A convenient method for the generation of negative and positive electrospray
      ionization mass spectra of proteins by gas-phase admission of volatile bases and
      acids via the nebulizing gas.

PMID- 11291127
TI  - Perioperative radiotherapy and concurrent radiochemotherapy in rectal cancer.
AB  - Combined modality treatment is the recommended standard adjuvant therapy for
      patients with locally advanced rectal cancer in the United States and Germany.
      During the last decade substantial progress has been made in treatment
      modalities, and surgical management currently includes a broad spectrum of
      operative procedures ranging from radical operations to innovative sphincter
      preserving techniques. Specialized groups have reported excellent local control
      rates with total mesorectal excision (TME) alone. New and improved radiation
      techniques (conformal and intraoperative radiotherapy) and innovative schedules
      (protracted intravenous and chronomodulated infusion) and combinations
      (oxaliplatin and irinotecan) of chemotherapy may have the potential to further
      increase the therapeutic benefit of adjuvant treatment. Moreover, the basic issue
      of timing (pre- or postoperative) within a multimodal regimen is currently being
      addressed in prospective trials. Evidently there is a need to question the
      current monolithic approaches, which were established by studies conducted more
      than a decade ago. It is also under discussion whether to apply the same schedule
      of postoperative radiochemotherapy to all patients with stage II/III rectal
      cancer, or to give preoperative intensive short-course radiation according to the
      Swedish concept for all patients with resectable rectal cancer irrespective of
      tumor stage and treatment goal (e.g., sphincter preservation). This review
      discusses different irradiation settings in more recent and ongoing studies of
      perioperative radiotherapy for rectal cancer, and focuses on the issue of which
      patient should receive radiotherapy (if at all), and if so, how and when.

PMID- 11291128
TI  - Postoperative radiotherapy of astrocytomas.
AB  - Astrocytomas account for the majority of primary brain tumors. Low-grade tumors
      are slowly growing tumors with relatively long overall survival. However, a high
      percentage of these tumors transform to more malignant, high-grade tumors. High
      grade gliomas (anaplastic astrocytomas and glioblastoma multiforme) have a poor
      prognosis. Treatment options are capable of prolonging the natural history of the
      disease, but the long-term survival is poor. This review discusses the different
      postoperative treatment options and the prognostic factors in low- and high-grade
      astrocytomas.

PMID- 11291129
TI  - Bladder preservation in muscle-invasive bladder cancer by conservative surgery
      and radiochemotherapy.
AB  - Organ preservation has been investigated in muscle-invasive bladder cancer over
      the past decades as an alternative to standard radical cystectomy. The results of
      large prospective protocols and population-based studies suggest that an organ
      preserving approach is possible without deferring the survival probability. Organ
      preservation requires a trimodal schedule, including transurethral surgery
      (transurethral resection of bladder tumor (TURBT)), radiation, and chemotherapy.
      A complete TURBT is the most important single prognostic factor, and should be
      attempted. Radiotherapy, in conjunction with concurrent platinum-based
      chemotherapy, can control the vast majority of urothelial bladder tumors. The
      histologically-proven complete remission rates of macroscopic tumors
      (unresectable by TURBT) lie in the range of about 70%. After radiochemotherapy, a
      histological response evaluation with repeated TURBT is recommended. Patients
      with residual tumor require salvage cystectomy. In cases of complete remission,
      patients can maintain their bladders but they should be closely followed over
      years. The risk of severe late-radiation sequelae is low, in the range of less
      than 5%. About 75% of long-term survivors maintain a normally functioning
      bladder.

PMID- 11291130
TI  - Perioperative radiotherapy for cancer of the esophagus.
AB  - Carcinomas of the esophagus represent on average about 1% to 2% of all malignant
      tumors. The incidence shows extreme regional differences, reflecting the
      established environmental and acquired risk factors for cancer of the esophagus.
      There has been a major shift in tumor location and histology over the last
      decades, with the lower third/gastroesophageal junction becoming the most common
      location and adenocarcinoma the most common histology in white males. There has
      been a striking improvement in surgical resection rates and operative mortality;
      however, the curative potential of surgery is likely to be highest in early-stage
      disease. The poor prognosis for locally advanced tumors motivated the search for
      multimodal approaches to improve results. While neither perioperative
      radiotherapy nor perioperative chemotherapy alone have significantly improved
      survival rates, combined radiochemotherapy, used as neoadjuvant or definitive
      therapy, appears more promising. For patients with advanced tumors or extensive
      nodal involvement, first principles and extrapolation from other tumors of the
      gastrointestinal tract suggest that a combination of chemotherapy and radiation
      is likely to be of benefit, as compared to surgery alone. As this treatment is
      difficult to tolerate in the postoperative setting, neoadjuvant approaches have
      been emphasized. Although there are promising data, and preoperative
      chemoradiation is widely utilized, we do not consider the benefit of this
      approach to have been proven unequivocally. Future progress in the treatment of
      esophageal cancer may require that systemic therapy be improved to the point
      where occult metastatic disease can be controlled, enabling the local control
      provided by surgery and radiation to lead to improved survival.

PMID- 11291131
TI  - Intraoperative radiotherapy for gastrointestinal cancer.
AB  - Local recurrence following potentially curative tumor resection is a major
      problem in patients with gastrointestinal cancer. To augment surgical excision
      and to avoid the disadvantages of external beam irradiation, intraoperative
      radiotherapy (IORT) has been applied to primary and recurrent gastrointestinal
      cancer, both with curative intent and for palliation. There is ample evidence
      that the combination of radical surgery and IORT can improve local control.
      Whether this eventually can translate into improved overall survival has not yet
      been studied in adequately powered randomized and controlled trials.

PMID- 11291132
TI  - Adjuvant treatment of brain metastases.
AB  - With an incidence of 15/10(5) in the general population, brain metastases
      constitute a serious, debilitating complication in cancer patients. The majority
      of those patients suffer from more than one metastasis, but up to 30% to 40%
      present with a solitary lesion. Whole-brain radiotherapy (WBRT) extends median
      survival from 1 to 2 months for treatment with steroids only, to 4 to 6 months in
      most series. However, long-term survival (>1-2 years) is observed in up to 10% of
      patients with favorable prognostic factors, such as solitary lesions, good
      Karnofsky performance status, and absence of extracranial disease. For those
      patients, individually optimized treatment is worthwhile. For good-prognosis
      patients with controlled extracranial disease, surgery in combination with
      postoperative WBRT should be considered, especially when fast relief of symptoms
      is mandated. For surgically inaccessible solitary lesions below a size threshold
      of approximately 30 ccm, stereotactic radiosurgery (RS), although never compared
      to surgery in a randomized fashion, seems to yield comparable results and is the
      treatment of choice for more than one lesion in appropriately selected patients.
      Nevertheless, a number of questions concerning the optimal treatment regimens for
      brain metastases remain. These mainly concern the radiation dose, need for a
      combination of RS and WBRT, relative timing of different treatment modalities,
      and maximum number of brain metastases that can reasonably be treated with RS
      when long-term progression-free survival is the goal. However, RS is definitely
      an excellent option for salvage and palliation in patients with short life
      expectancy, as it is simultaneously noninvasive and cost-effective, with short
      hospitalization times.

PMID- 11291133
TI  - Contemporary role of modern brachytherapy techniques in the management of
      malignant thoracic tumors.
AB  - Sole brachytherapy for carcinoma of the lung is most often performed using high
      dose-rate (HDR) remote afterloading equipment, which delivers the treatment
      within the tracheobronchial tree in an outpatient setting. It provides excellent,
      rapid palliation in advanced stages, and can also be used selectively for
      curative intent in early stages. In better-performance patients, fractionated
      external beam radiation therapy (EBRT) is preferred to brachytherapy as an
      initial treatment because it appears to provide a modest gain in survival, and
      more sustained palliation. In patients with centrally located tumors and limited
      extent of disease, the combination of external and endoluminal irradiation
      enables curative treatment options. Intraoperative brachytherapy may complement
      standard adjuvant treatment in incompletely resected, unresectable, or medically
      inoperable patients, and has the potential to improve local control in selected
      cases. Due to the rarity of the disease, the role of endoluminal brachytherapy in
      the treatment regimen of tracheal neoplasms is not yet clearly defined. The risk
      of fatal bleeding after endoluminal brachytherapy appears to be correlated with
      tumor localization and fraction size, but in the majority of cases fatal bleeds
      are caused by progression of local disease. The use of a distanceable applicator
      provides a central positioning of the source, prevents the delivery of high
      contact doses to the mucosa, and may reduce toxicity. The standard technique for
      interstitial brachytherapy after breast-conserving surgery and adjuvant EBRT is
      the use of low-dose-rate (LDR) brachytherapy, but it may also be applied by means
      of pulsed-dose-rate (PDR) or HDR techniques. Prospective trials comparing
      different boost techniques and indications are needed to define more precisely
      the subgroup of patients who are most suitable for interstitial brachytherapy.
      Reirradiation of chest wall local recurrences using brachytherapy molds is
      effective and provides a high local control rate with acceptable toxicity.

PMID- 11291134
TI  - Role of multimodal treatment in oropharynx, larynx, and hypopharynx cancer.
AB  - Due to recent advances in radiation fractionation, radiochemotherapy, and
      conservative surgical techniques, the concept of multimodal therapy in head and
      neck cancer is currently changing. The recently published RTOG Phase III trial
      9003, with 1,113 patients accrued, showed that hyperfractionation and accelerated
      fractionation with concomitant boost are more efficacious than standard
      fractionation for locally-advanced head and neck cancer. Acute, but not late,
      toxicity was also increased. Three meta-analyses have suggested that the impact
      of chemotherapy in head and neck cancer is small but is highly associated with
      the timing of therapy. Concomitant administration of radiation therapy and
      chemotherapy led to an absolute benefit in 5-year survival of about 10%. This
      finding has been further supported by recently published randomized prospective
      trials comparing concomitant radiochemotherapy with radiotherapy alone in
      advanced head and neck cancer. There is now clear evidence that radiochemotherapy
      provides a substantial and statistically significant improvement in survival and
      local-regional control, as compared to radiotherapy alone. Radiochemotherapy
      should be considered an accepted standard of care in cancers of the oropharynx,
      particularly for patients with locally-advanced disease who have a good
      performance status. Two randomized studies conducted by the Department of
      Veterans' Affairs and the EORTC, with a total of 534 patients accrued, showed
      that induction chemotherapy followed by radiotherapy of responders yields
      survival rates equal to those of total laryngectomy with postoperative
      radiotherapy. After 4 years, one-half to two-thirds of survivors of the
      chemotherapy arm retained a functional larynx. Larynx preservation using
      induction chemotherapy can now be regarded as feasible but still investigational.
      Current phase II studies show excellent larynx preservation rates using a primary
      concomitant radiochemotherapy with an altered fractionation regimen. More
      clinical and laboratory research is required to further evaluate the different
      treatment options of the multimodality concept, and to develop prognostic models
      that will allow individualization of the therapy.

PMID- 11291135
TI  - AIA (American Institute of Architects) 2001 guidelines and indoor air health.

PMID- 11291136
TI  - Things you can do to protect your facility against lawsuits. Part I: Avoiding
      clinical risks.

PMID- 11291137
TI  - Are your restraint policies setting you up for immediate jeopardy citations?

PMID- 11291138
TI  - Report on Texas nursing facilities raises new questions about quality of care,
      survey and enforcement.

PMID- 11291139
TI  - Nursing facilities will have to comply with strict privacy rules protecting
      personal health information.

PMID- 11291140
TI  - Improve your compliance record in 2001.

PMID- 11291141
TI  - Making your way through the enforcement process.

PMID- 11291142
TI  - HCFA to crack down on use of chemical restraints.

PMID- 11291143
TI  - Five things you should never do during or after a survey.

PMID- 11291144
TI  - Influential research group says quality of care in many nursing homes continues
      to be problematic.

PMID- 11291145
TI  - Why do nursing homes get sued?

PMID- 11291146
TI  - Things you can do to protect your facility against lawsuits. Part III: Avoiding
      documentation risks.

PMID- 11291147
TI  - Resident assessment tool confusing, says OIG.

PMID- 11291148
TI  - [The elusive pathogen. How dangerous is mold? (interview by Dr. Christina
      Berndt)].

PMID- 11291149
TI  - [Patient heart complaints of organic or functional origin? Anamnesis discloses
      more than equipment].

PMID- 11291150
TI  - [Lowering blood pressure--preventing 4 out of 10 strokes. Fully utilizing
      antihypertensive therapy].
AB  - The greatest profit of antihypertensive drug therapy consists in avoiding stroke.
      The blood pressure aimed at should be below 140/90 mmHg, in diabetic patients
      below 135/80 mmHg. There exist no special recommendations concerning the choice
      between the various antihypertensive drugs in use. As a matter of fact, it is
      advantageous to use in diabetic patients primarily ACE-inhibitors, if necessary
      in combination with calcium-antagonists. The profit of antihypertensive therapy
      in avoiding stroke is also proved among elderly patients. All vascular risks
      should be treated. In case of atrial fibrillation and of asymptomatic high-grade
      restriction of the carotic artery the indication for a surgical treatment
      respectively for a therapy with antiaggregating drugs should be considered.
      Secondary prevention: Hypertension after a cerebral ischemia increases the risk
      of a recurrent ischemic event. Antihypertensive therapy may probably reduce the
      risk of a recurrent stroke. Analyses performed so far are only incomplete on this
      subject. For the first time, the PROGRESS-study will show exact data. Special
      recommendations concerning the choice between the various antihypertensive drugs
      in use do not exist neither. Therefore, the recommendations of the German
      Hypertension League for secondary prevention correspond with those for primary
      prevention. Hypertension increases the risk of developing dementia.
      Antihypertensive therapy may apparently reduce significantly the risk of
      developing dementia. A further important aspect is non-dipping at sleep which is
      correlated with a worse prognosis of patients.

PMID- 11291151
TI  - [When lowering blood pressure is risky. Cerebral infarct--the paradox of
      prevention and acute therapy].
AB  - The value of a sustained lowering of elevated blood pressure below 140/80 mmHg
      for primary and secondary prevention of stroke has been demonstrated in
      controlled studies. In contrast, active lowering of blood pressure in the acute
      phase of a cerebral infarction is associated with the risk of causing further
      damage to the brain by reducing perfusion in the region of disordered vascular
      autoregulation surrounding the ischemic area ("penumbra"). The recommendations of
      a European Consensus Conference therefore apply, that in the first three days
      following an acute stroke the blood pressure should be cautiously lowered only
      when a systolic pressure of 220 mmHg or a diastolic pressure of 120 mmHg is
      exceeded.

PMID- 11291152
TI  - [Internet addresses on the main topic. Stroke and hypertension].

PMID- 11291153
TI  - [Prognosis of the diabetic patient with nephropathy is catastrophic. Don't let it
      get that far!].

PMID- 11291154
TI  - [Confusion in delirium. How orientation to space and time gets lost].

PMID- 11291155
TI  - [Thrombophilia diagnosis: when and how? Thrombosis ABC, 9: Genetically-induced
      thrombosis susceptibility].

PMID- 11291156
TI  - [Counseling before and in pregnancy. 6: Virus diagnosis before pregnancy].

PMID- 11291157
TI  - [Problem patients with atopic eczema consulting the physician].

PMID- 11291158
TI  - [Diagnostic quiz. Enlarged heart with pulsus paradoxus. Dissecting aneurysm of
      the ascending aorta with large pericardial effusion].

PMID- 11291159
TI  - [Medicine in Europe after the turn of the century. Your practice becomes branch
      model].

PMID- 11291160
TI  - [Multiple prevention. On the way to an ideal antihistamine?].

PMID- 11291161
TI  - [Migraine therapy. Help for the head--without risk for to the heart].

PMID- 11291162
TI  - [Diabetes in childhood and puberty. Initial education is a decisive factor].

PMID- 11291163
TI  - [Better endothelial function, fewer ischemic problems. An ACE inhibitor provides
      protection against ischemia].

PMID- 11291164
TI  - [What the drug industry offers physicians on the internet. Online address on the
      topic of travel medicine].

PMID- 11291166
TI  - Defining a hybrid.

PMID- 11291165
TI  - Defined contribution health benefits.
AB  - This Issue Brief discusses the emerging issue of "defined contribution" (DC)
      health benefits. The term "defined contribution" is used to describe a wide
      variety of approaches to the provision of health benefits, all of which have in
      common a shift in the responsibility for payment and selection of health care
      services from employers to employees. DC health benefits often are mentioned in
      the context of enabling employers to control their outlay for health benefits by
      avoiding increases in health care costs. DC health benefits may also shift
      responsibility for choosing a health plan and the associated risks of choosing a
      plan from employers to employees. There are three primary reasons why some
      employers currently are considering some sort of DC approach. First, they are
      once again looking for ways to keep their health care cost increases in line with
      overall inflation. Second, some employers are concerned that the public
      "backlash" against managed care will result in new legislation, regulations, and
      litigation that will further increase their health care costs if they do not
      distance themselves from health care decisions. Third, employers have modified
      not only most employee benefit plans, but labor market practices in general, by
      giving workers more choice, control, and flexibility. DC-type health benefits
      have existed as cafeteria plans since the 1980s. A cafeteria plan gives each
      employee the opportunity to determine the allocation of his or her total
      compensation (within employer-defined limits) among various employee benefits
      (primarily retirement or health). Most types of DC health benefits currently
      being discussed could be provided within the existing employment-based health
      insurance system, with or without the use of cafeteria plans. They could also
      allow employees to purchase health insurance directly from insurers, or they
      could drive new technologies and new forms of risk pooling through which health
      care services are provided and financed. DC health benefits differ from DC
      retirement plans. Under a DC health plan, employees may face different premiums
      based on their personal health risk and perhaps other factors such as age and
      geographic location. Their ability to afford health insurance may depend on how
      premiums are regulated by the state and how much money their employer provides.
      In contrast, under a DC retirement plan, employers' contributions are based on
      the same percentage of income for all employees, but employees are not subject to
      paying different prices for the same investment.

PMID- 11291167
TI  - Preventing errors. Pharmacist assist.

PMID- 11291168
TI  - Risk management. Cyber liability.

PMID- 11291170
TI  - Medical devices. Infusion confusion.

PMID- 11291169
TI  - Public policy. New life for MSAs?

PMID- 11291171
TI  - Patient satisfaction. Survey says?

PMID- 11291172
TI  - Privacy monitor. Help wanted.

PMID- 11291173
TI  - Direct contracting. Deja new.

PMID- 11291174
TI  - HIPPA coding. Costly code conversion dodged.

PMID- 11291175
TI  - All the right moves.

PMID- 11291176
TI  - Leadership survey.

PMID- 11291177
TI  - Our overburdened ERs.
AB  - Like meteorologists tracking powerful weather systems, hospital officials have
      watched uneasily for some time as pressures built. The rising number of
      uninsured, a nursing shortage, lower reimbursements, and more and sicker hospital
      patients all brought turbulence. Now a convergence of these and other factors
      poses a serious challenge to emergency rooms, raising concerns about the
      stability of the nation's health care delivery system.

PMID- 11291178
TI  - Doctor dearth.

PMID- 11291179
TI  - Seeing red in the golden state.

PMID- 11291180
TI  - Defined conundrum.

PMID- 11291181
TI  - The processing of coreference for reduced expressions in discourse integration.
AB  - Three reading-time experiments in Chinese are reported that test contrasting
      views of how pronominal coreference is achieved. On the one hand, studies of
      reading time and eye tracking suggest that reduced expressions, such as the
      pronoun he, serve as critical links to integrate separate utterances into a
      coherent model of discourse. On the other hand, probe-word recognition studies
      indicate that full anaphoric expressions, such as a repeated name, are more
      readily interpreted than reduced expressions due to their rich lexical
      information, which provides effective cues to match the representation of the
      appropriate referent in memory. The results indicate that the ease of integrating
      the critical referent into a model of discourse is a function of the congruence
      of lexical, semantic, and discourse features conveyed by a syntactically
      prominent reduced expression within linguistic input. This pattern supports the
      view that a reduced expression is interpreted on-line and indeed plays a critical
      role in promoting discourse coherence by facilitating the semantic integration of
      separate utterances.

PMID- 11291182
TI  - Misinterpretations of garden-path sentences: implications for models of sentence
      processing and reanalysis.
AB  - Theories of sentence comprehension have addressed both initial parsing processes
      and mechanisms responsible for reanalysis. Three experiments are summarized that
      were designed to investigate the reanalysis and interpretation of relatively
      difficult garden-path sentences (e.g., While Anna dressed the baby spit up on the
      bed). After reading such sentences, participants correctly believed that the baby
      spit up on the bed; however, they often confidently, yet incorrectly, believed
      that Anna dressed the baby. These results demonstrate that garden-path reanalysis
      is not an all-or-nothing process and that thematic roles initially assigned for
      the subordinate clause verb are not consistently revised. The implications of the
      partial reanalysis phenomenon for Fodor and Inoue's (1998) model of reanalysis
      and sentence processing are discussed. In addition, we discuss the possibility
      that language processing often creates "good enough" structures rather than ideal
      structures.

PMID- 11291183
TI  - The declarative/procedural model of lexicon and grammar.
AB  - Our use of language depends upon two capacities: a mental lexicon of memorized
      words and a mental grammar of rules that underlie the sequential and hierarchical
      composition of lexical forms into predictably structured larger words, phrases,
      and sentences. The declarative/procedural model posits that the lexicon/grammar
      distinction in language is tied to the distinction between two well-studied brain
      memory systems. On this view, the memorization and use of at least simple words
      (those with noncompositional, that is, arbitrary form-meaning pairings) depends
      upon an associative memory of distributed representations that is subserved by
      temporal-lobe circuits previously implicated in the learning and use of fact and
      event knowledge. This "declarative memory" system appears to be specialized for
      learning arbitrarily related information (i.e., for associative binding). In
      contrast, the acquisition and use of grammatical rules that underlie symbol
      manipulation is subserved by frontal/basal-ganglia circuits previously implicated
      in the implicit (nonconscious) learning and expression of motor and cognitive
      "skills" and "habits" (e.g., from simple motor acts to skilled game playing).
      This "procedural" system may be specialized for computing sequences. This novel
      view of lexicon and grammar offers an alternative to the two main competing
      theoretical frameworks. It shares the perspective of traditional dual-mechanism
      theories in positing that the mental lexicon and a symbol-manipulating mental
      grammar are subserved by distinct computational components that may be linked to
      distinct brain structures. However, it diverges from these theories where they
      assume components dedicated to each of the two language capacities (that is,
      domain-specific) and in their common assumption that lexical memory is a rote
      list of items. Conversely, while it shares with single-mechanism theories the
      perspective that the two capacities are subserved by domain-independent
      computational mechanisms, it diverges from them where they link both capacities
      to a single associative memory system with broad anatomic distribution. The
      declarative/procedural model, but neither traditional dual- nor single-mechanism
      models, predicts double dissociations between lexicon and grammar, with
      associations among associative memory properties, memorized words and facts, and
      temporal-lobe structures, and among symbol-manipulation properties, grammatical
      rule products, motor skills, and frontal/basal-ganglia structures. In order to
      contrast lexicon and grammar while holding other factors constant, we have
      focused our investigations of the declarative/procedural model on morphologically
      complex word forms. Morphological transformations that are (largely) unproductive
      (e.g., in go-went, solemn-solemnity) are hypothesized to depend upon declarative
      memory. These have been contrasted with morphological transformations that are
      fully productive (e.g., in walk-walked, happy-happiness), whose computation is
      posited to be solely dependent upon grammatical rules subserved by the procedural
      system. Here evidence is presented from studies that use a range of
      psycholinguistic and neurolinguistic approaches with children and adults. It is
      argued that converging evidence from these studies supports the
      declarative/procedural model of lexicon and grammar.

PMID- 11291184
TI  - Agrammatism and the psychological reality of the syntactic tree.
AB  - Syntactic trees, or phrase markers, have originally been suggested as a
      representation of syntax in the mind based on purely linguistic grounds. In this
      paper, the psychological reality of syntactic trees and hierarchical ordering is
      explored from another perspective--that of the neuropsychology of language
      breakdown. The study reported here examined several syntactic domains that rely
      on different nodes in the tree--tense and agreement verb inflection,
      subordinations, interrogatives, and verb movement, through a study of 14 Hebrew-
      and Palestinian Arabic-speaking agrammatic aphasics and perusal of the cross
      linguistic literature. The results show that the impairment in agrammatic
      production is highly selective and lends itself to characterization in terms of a
      deficit in the syntactic tree. The complex pattern of dissociations follows from
      one underlying deficit--the inaccessibility of high nodes of the syntactic tree
      to agrammatic speakers. Structures that relate to high nodes of the tree are
      impaired, while "lower" structures are spared.

PMID- 11291185
TI  - Semantic factors in the production of number agreement.
AB  - This paper examines the role of semantic factors in the production of subject
      verb number agreement. As an ostensibly grammatical process, number agreement
      provides an interesting case for examining the flow and interaction of semantic
      and syntactic information through the language-production system. Using a
      sentence-completion task, agreement errors can be elicited from subjects by
      presenting them with sentence fragments containing a complex noun-phrase, in
      which the nonhead noun is plural (e.g., The key to the cabinets ... WERE
      missing.). Previous research has demonstrated that the probability of making an
      error can be affected by varying the properties of the nouns in the complex noun
      phrase. By investigating which variables do and do not affect error rates,
      constraints on the flow of information through the production system can be
      inferred. In three experiments, we investigated the possible effects of three
      different semantic manipulations of the nouns in the complex NP: animacy,
      semantic overlap, and plausibility of modification by the sentence predicate. We
      found that both animacy and semantic relatedness had reliable effects on error
      rates, indicating that the mechanism involved in implementing agreement cannot be
      blind to semantic information. However, the plausibility with which each noun
      could serve as the subject of the sentence predicate had no effect on error
      rates. Taken together, these results suggest that while semantic information is
      visible to the agreement mechanism, there are still constraints on when this
      information can affect the process. Specifically, it may be the case that only
      information contained within the complex NP is considered for the purposes of
      implementing agreement.

PMID- 11291186
TI  - Training psychotherapists in attributes of "mind" from Zen and psychoanalytic
      perspectives, Part I: Core principles, emptiness, impermanence, and paradox.
AB  - This paper outlines the principles of a conceptual foundation for an innovative
      approach to the training of the modern psychotherapist, using certain technical
      and philosophical percepts found in the practice of Zen, divorced from its usual
      role as a form of Buddhism and/or a religious belief. A set of core principles
      derived from Zen and embedded in psychoanalytic theory are listed. Specific
      values are embodied in the day to day practice of the psychotherapist. The first
      of these values is the understanding of the true nature of emptiness in relation
      to the self and the non-Cartesian universe. Then the concept of impermanence and
      the centrality of paradox to the practice of Zen and psychotherapy is described.
      The basis of this approach to the education of the psychotherapist is grounded in
      the assumption that the usual training format with its focus on training in
      technical skills, with personal treatment being an additional requirement for
      many psychodynamic therapists, is insufficient for a complete educational
      experience. The training of the mind itself is an often forgotten and yet
      essential component of the training process.

PMID- 11291187
TI  - Schizoid anxiety: a reappraisal of the manic defense and the depressive position.
AB  - The author views the manic defense as a combined attempt to control persecutory
      objects and to save them from the aggressive forces within the ego. Rather than
      strictly a manifestation of depressive guilt, it is also a defense against the
      fear of destroying the object and subsequently the self. Therefore, Melanie
      Klein's depressive position is a hierarchical outgrowth of more primitive
      schizoid anxieties about killing off the ideal part object. This is contrasted
      with the depressive guilt of harming the whole and reliable object. The
      depressive position is a psychic state of worry about loss of the object's love
      resulting from temporary harm done to the object that can be fixed. The paranoid
      schizoid position is a much more hopeless internal situation involving a complete
      loss of the object and, by extension, the self. A case study is used for
      illustration.

PMID- 11291188
TI  - Psychotherapy in consultation-liaison psychiatry.
AB  - Psychotherapy in the Consultation-Liaison (C-L) setting is shaped by the
      realities of the patient's situation, since all patients referred are dealing
      with physical illness. The patient's state of physical and mental health will
      determine both the type of therapeutic work possible and the focus of such work.
      Tailoring the therapeutic intervention to the patient's specific needs and
      flexibility in altering and adapting therapeutic strategies over time in line
      with the patient's changing needs are essential. Although periods of treatment
      may range from single session to long term, supportive, insight oriented, group,
      family, cognitive and behavioral techniques have all been used successfully in a
      C-L setting, with measurable impact on well-being. Psychotherapeutic work in C-L
      is unique in that the focus of the therapist extends beyond the patient and
      family to include all caregivers, including other health care professionals, in
      line with the biopsychosocial model.

PMID- 11291189
TI  - Training psychotherapists in attributes of "mind" from Zen and psychoanalytic
      perspectives, Part II: Attention, here and now, nonattachment, and compassion.
AB  - Part II of this paper enumerates four additional attributes of mind derived from
      Zen that could enrich the training of a psychotherapist. These include: training
      and modulation of the therapist's attention, the centrality of the concept of
      "here and now," what it is and is not, and the natural unpressured emergence of
      compassion as a manifestation of the therapist's nature.

PMID- 11291190
TI  - Felicia's journey: an object-relational study of psychopathy.
AB  - This paper examines Atom Egoyan's film, Felicia's Journey, based on the novel of
      the same name by William Trevor, from an object-relational viewpoint. The
      protagonist's characteristic defense mechanisms of splitting, projection, and
      denial, which are characteristic of the schizoid position, are explored in depth,
      as are the antecedents of this behavior, as seen in his early relationship with
      his mother. Finally, the relationship between his psychopathy and his functioning
      in the schizoid position is considered.

PMID- 11291191
TI  - Rediscovering existential psychotherapy: the contribution of Ludwig Binswanger.
AB  - Ludwig Binswanger, a founder of the existential school of psychiatry, attempted
      to apply philosophical ideas derived from Martin Heidegger, such as Heidegger's
      views on the mind-body problem, to the understanding and treatment of psychiatric
      patients. Binswanger also interpreted Heidegger's concept of the existing
      individual (Dasein) as Being-in-the-World, in the sense of seeking out the
      existential structure of individuals' lives. I discuss concrete clinical cases
      from Binswanger's work, along with a contemporary example of how to use these
      existential methods in psychiatric practice.

PMID- 11291192
TI  - The narcissistic function in obsessive-compulsive neurosis.
AB  - Freud's intrapersonal concept of anal-sadistic regression is set against the
      interpretation of obsessive-compulsive neurosis as a structural ego deficit. The
      interpersonal dimension that comes to the fore as a result of this, becomes clear
      if we focus on obsessive-compulsive behavioral disorder: Persons suffering from
      obsessive-compulsive neurosis lack the self-assessment factor. It needs another
      person as part of their own ego who accepts and supports them in their behavior.
      A clinical example illustrates this narcissistic function of compulsion together
      with the changes in the psychodynamic approach and resulting therapy. Against DSM
      classification with the concept of obsessive-compulsive disorder, which contains
      an unspecific symptomatology that occurs both in neurosis, schizophrenia,
      melancholia, and organic psychosis, this article advocates the specific and
      differentiated concept of obsessive-compulsive neurosis.

PMID- 11291193
TI  - General introduction to the psychotherapy of Pierre Janet.
AB  - This article deals with Pierre Janet's concept of "Psychological Analysis"
      (analyse psychologique). It brings out Janet's criticism of Sigmund Freud's
      ideas, and delineates the difference between psychological analysis (Janet) and
      psychoanalysis (Freud). Further it points out that Janet's theories on the
      pathogenesis of neurotic disorders rely on the concept of psychic trauma and
      associated fixed ideas. Mental force and mental tension, described in greater
      detail, are essential for the pathogenesis of mental disorders. According to
      Janet, a significant characteristic of the neurotically disturbed person is a
      feature that Von Gebsattel calls "Werdenshemmung" ("inhibition of becoming"), a
      state which impairs the life development of the ill person.

PMID- 11291194
TI  - Re-minding the body.
AB  - The author discusses a fragment of the analysis of a patient who had experienced
      both neglect and sexual molestation during early childhood. The analysand had
      developed a defensively hypertrophied form of mindedness in an effort to gain
      some sense of control over bodily experience, which threatened not only his
      sanity, but his very sense of being. The focus of the paper is on a series of
      sessions from a period of regression during which the patient experienced
      psychotic-level anxiety and a feeling of impending psychic disintegration. The
      author discusses in detail two interventions that he made during this period of
      analytic work. The first involved the analyst's finding himself speaking with a
      parental voice with which he took on the responsibility of protectively "minding"
      the patient while the patient experienced himself on the edge of disintegration.
      The second spontaneous intervention involved the analyst's inviting the patient
      to imagine himself at his present age into a story of molestation (based on the
      patient's history and the history of the analysis) in which the analyst was a
      third presence bearing witness, bearing language and bearing compassion. These
      interventions seemed to have been of importance in facilitating the patient's
      development of a greater sense of being alive in a co-extensive minded body and
      bodied mind.

PMID- 11291195
TI  - Web watch.

PMID- 11291196
TI  - Delaware's medicolegal investigation of death. Part 2.
AB  - Part 1 of this series began in 1194, when the coroner system was formally
      established in England with the original interest in death to protect the
      financial interest of the crown. This coroner system was brought to the United
      States during the early 1600s where the first recorded autopsy was performed in
      Massachusetts in 1647. Significant changes were made to improve upon the coroner
      system. In 1877, the first medical examiner system was established in the state
      of Massachusetts, requiring that the coroner be supplanted by a physician known
      as a medical examiner. Using the system established in Massachusetts as a model,
      New York City developed an improved medical examiner system in 1915. The
      improvements made by New York City, under the leadership of men such as Drs.
      Charles Norris and Alex Gettler, essentially laid down the foundation for medical
      examiner systems and forensic toxicology throughout the country. Part 2 of this
      series begins in Maryland. Maryland soon followed in New York City's footsteps
      and in 1939 developed the first statewide medical examiner system in the U.S.
      Influenced by systems such as Maryland's and New York City's, Delaware
      established a medical examiner system in 1955 to work alongside of the pre
      existing coroner system. It was not until about a decade later, in 1964, that the
      system became successful under the leadership of Dr. Ali Z. Hameli. In 1970,
      after 15 years of uphill battles with supporters of the antiquated coroner
      system, it was abolished, resulting in a statewide medical examiner system.
      Today, Delaware's medical examiner system has one of the best medicolegal
      investigative facilities in the country, complete with its own forensic sciences
      laboratory under the jurisdiction of a Chief Medical Examiner. Delaware's Office
      of Chief Medical Examiner will try to continue its tradition to serve as a model
      for other states and possibly other countries to follow.

PMID- 11291197
TI  - The pilgrimage to Mecca.

PMID- 11291198
TI  - Evaluation of critical binder properties affecting the compactibility of binary
      mixtures.
AB  - The aim of this study was to identify essential physical and mechanical
      properties of various binders and to investigate their influence on the tensile
      strength and porosity of tablets made from binary mixtures with sodium
      bicarbonate. The binders were characterized according to axial and radial tensile
      strength after compression into tablets, yield pressure and minimum porosity
      during compression, and elastic recovery after compression. The addition of a
      binder generally resulted in an increase in the tensile strength and a decrease
      in the porosity of the sodium bicarbonate tablets. The location of the binder in
      the voids between the sodium bicarbonate particles thus decreasing the porosity
      of the tablet seemed to be an important consideration. Consequently, the addition
      of binders with a low yield pressure value and a relatively small elastic
      recovery value (e.g., polyethylene glycol 3000 and polyvinylpyrrolidone) resulted
      in tablets of low porosity and high tensile strength, especially in the axial
      direction. The tensile strength of the pure binder also seemed to be important,
      especially for binders with a lower degree of deformability (e.g.,
      microcrystalline cellulose and pregelatinised starch). The results also indicated
      the value of using both axial and radial tensile strength measurements in
      assessing the effect of a dry binder and showed that the importance of different
      binder properties varied according to the direction of the tablet strength
      measurements. The results demonstrated that the applied characteristics of the
      binders used in this study may serve as a useful tool in evaluating the
      effectiveness of binders.

PMID- 11291199
TI  - Spray-drying as a method for microparticulate controlled release systems
      preparation: advantages and limits. I. Water-soluble drugs.
AB  - Spray-drying was used for the preparation of paracetamol/eudragit RS or RL or
      ethylcellulose microspheres to verify the possibility of their use in controlled
      release solid-dosage forms formulation and try to determine advantages and limits
      of the technique of such use. Microspheres were first characterized by scanning
      electron microscopy, differential scanning calorimetry, x-ray diffractometry, and
      in vitro dissolution studies and then used for the preparation of tablets. During
      this step, the compressibility of the spray-dried powders was also evaluated. In
      vitro dissolution studies were performed also on the tablets and their release
      control was accessed. Although powders were unable to slow down drug release,
      tablets obtained from microsphere compression showed a good capability of
      controlling paracetamol release when eudragit RS or ethylcellulose was used, even
      at low polymer amounts.

PMID- 11291200
TI  - Deposition of nacystelyn from a dry powder inhaler in healthy volunteers and
      cystic fibrosis patients.
AB  - The aim of this study was to compare, using gamma scintigraphy, the lung
      deposition of a novel mucoactive agent, Nacystelyn (NAL), administered as a dry
      powder inhaler (DPI) in six healthy volunteers, six adult patients with cystic
      fibrosis (CF), and six children and adolescents patients with CF. The correlation
      between in vitro and in vivo results was also tested. It was first demonstrated
      that the method of labeling of NAL with 99mTc was reliable as tested by three in
      vitro methods (multistage liquid impinger, multistage cascade impactor, and 2
      stage glass impinger). The deposition of unlabeled NAL, labeled NAL, and the
      radiolabel was similar in all stages of each device. Furthermore, the fine
      particle fraction (FPF) was the same on all apparatuses. The mean lung deposition
      obtained in volunteers was 27.5 +/- 13.5%. The results are approximately three
      times higher than the results obtained previously in healthy volunteers with NAL
      metered-dose inhalers (MDIs). As expected, the lung deposition observed in
      patients with CF was lower, e.g., 23.5 +/- 7.0% for adults and 16.5 +/- 5.9% for
      children and adolescents. A significant correlation was found between lung
      deposition and both the patient weight (p < 0.02) and height (p < 0.04).
      Surprisingly, the peripheral:central (P:C) ratio was similar for the three
      populations, indicating that the presence of mucus in moderately ill patients
      with CF does not modify the lung distribution of NAL. The FPF measured in vitro
      was similar to that obtained in volunteers but higher than that found in both
      patient populations. The DPI formulation of NAL developed will probably improve
      patient compliance and comfort in future clinical trials and postmarketing use of
      the drug.

PMID- 11291201
TI  - Evaluation of the tablet coating by the conventional spouted-bed process.
AB  - The purpose of this paper was to present an analysis of the tablet coating by the
      conventional spouted-bed process. To analyze the equipment performance, the rate
      of increase of the tablets mass, K1, and the adhesion coefficient eta were
      determined as a function of the feed flow rate of coating suspension Ws; of the
      Reynolds number Rep; of the flow rate of atomizing gas Wat, and of the cone base
      angle gamma. To analyze the product quality, the uniformity of coating mass
      deposition onto the tablet's surface was used. Three different procedures for
      description of kinetics growth, weighing method, image analysis, and measurements
      with a micrometer were used to verify the validity of the commonly used weighing
      method. Comparison between experimental results of kinetics growth with estimates
      obtained by a literature model was also performed. A tendency toward an increase
      in K1 and in eta with the feeding flow rate of coating suspension Ws was
      detected. The weighing method can be used for the process analysis. The kinetics
      of growth can be described by the growth model used. The variable that produce
      more pronounced effect on K1 and eta was the feed flow rate of coating
      suspension, the weighing method describes very well the increase of particle
      diameter with coating time, the growth model can be used for the describe the
      kinetics of growth during the coating operation, and the coating does not deposit
      uniformly onto the tablet's surface.

PMID- 11291202
TI  - Naproxen availability from variable-dose and weight sustained-release tablets.
AB  - The aim of this work was to compare the naproxen availability from hydroxypropyl
      methylcellulose (HPMC) matrix tablets containing the same dose and a 2-fold
      weight variation (160 mg of naproxen in tablets weighting 250 and 500 mg) or with
      the same weight and a 2-fold dose variation (500 mg of weight and 160 or 320 mg
      of naproxen). The 2-fold weight variation in tablets with the same dose and also
      the 2-fold dose variation in tablets with the same weight did not affect the
      naproxen release. In addition, the release rate of two tablets of the same
      formulation and one tablet with a 2-fold dose and weight variation was not
      significantly different at the first minutes of the dissolution assay.

PMID- 11291203
TI  - Thermodynamic analysis of water interaction with excipient films.
AB  - The interaction of water with excipients that can form moisture-protective
      coatings was examined earlier by the application of theoretical models. In this
      study, thermodynamic analysis of water-excipient film systems has been performed
      to elucidate the mechanistic details of the water-excipient interaction. Partial
      molal free energies, enthalpies, and entropies were computed for films of lipidic
      (glyceryl behenate, GB) and polymeric (polyvinyl alcohol, PVA) coating excipients
      using the temperature dependence of the adsorption process. The analysis of free
      energy changes showed that excipient films were not inert participants in the
      water sorption process. The isoteric heats of adsorption confirmed that water
      formed hydrogen bonds with the excipient films and allowed estimation of number
      of hydrogen bonds per water molecule. This result also provided the reason for
      hysteresis during drying. A comparative evaluation of the application of
      theoretical models and thermodynamic analysis revealed that results obtained from
      both approaches were not always complementary. An exponential relationship was
      found to exist between sorption microrate constants and water activity for the
      PVA films at all temperatures.

PMID- 11291204
TI  - Hot-melt coating: water sorption behavior of excipient films.
AB  - Hot-melt coating allows encapsulation of water-labile, drug-laden substrates to
      form a barrier that resists moisture ingress. To understand the interaction of
      water with excipients that can form moisture-protective coatings, sorption
      behavior of films of lipidic (glyceryl behenate) and polymeric (polyvinyl
      alcohol) coating excipients was investigated. A simple and rapid method using a
      new, fully automated instrumental technique to investigate the
      sorption/desorption behavior of excipient films is reported. Further, the
      influence of temperature and film thickness on the sorption behavior of films is
      examined. Both excipient films displayed sorption isotherms that were classified
      as type III and demonstrated hysteresis during desorption. The sorption data for
      both films did not follow the Langmuir model, and the BET model could only be
      used restrictively. The GAB model fitted the sorption data at all conditions and
      over the entire range of water activity studied. The ability of the Young and
      Nelson model to explain the hysteresis behavior, from analytical and mechanistic
      perspectives, is evaluated. Temperature and film thickness were found to
      profoundly influence the nature of moisture interaction and distribution of
      moisture in the excipient films. An Arrhenius-type relationship was observed
      between equilibrium moisture content of excipient films and temperature at
      constant water activity.

PMID- 11291205
TI  - Interaction of tenoxicam with cyclodextrins and its influence on the in vitro
      percutaneous penetration of the drug.
AB  - Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1:1 molar
      ratio, were obtained by the coprecipitation method and characterized by x-ray
      diffractometry, infrared spectroscopy, and differential scanning calorimetry. The
      binding capacity of the CDs with TEN was also demonstrated in aqueous solution
      and in water-propylene glycol mixtures. The purpose of this study was to
      determine the effect of CDs on the in vitro percutaneous penetration of TEN from
      carbopol gels, taking into account the role of the CD cavity size and the nature
      of the substituents. The effect of pretreatment was studied too. In vitro
      permeation experiments were carried out on Franz diffusion cells using cellulose
      nitrate membranes and abdominal rat skin. In these results, the release rates of
      the drug scarcely decreased when the CDs were added, probably because of a lower
      concentration of the free drug and an increased gel viscosity. However, it was
      also found that CDs, particularly gamma-CD and M-beta-CD, can improve slightly
      TEN absorption through the skin. Pretreatment studies with CDs, however, provided
      no effects on TEN permeation, but lag time was markedly reduced, suggesting a
      faster partitioning of TEN into the skin. Therefore, the use of pretreatment with
      CDs would be interesting when a quick action of the drug is desired.

PMID- 11291206
TI  - Dissolution test for silymarin tablets and capsules.
AB  - Silybine (SBN), isosilybine (ISBN), silycristine (SCN), silydianine (SDN), and
      taxifoline (TXF) are the main active flavonoids commonly found in the dried
      fruits of Silybum marianum, Gaertner (Compositae). Concentrations of these
      compounds, except TXF, are usually expressed together as silymarin content. This
      paper describes a simple dissolution test developed to estimate silymarin (Sl) in
      pharmaceutical formulations. Five commercial products were tested using this new
      method (including tablets, sugar tablets, and capsules): two from Argentina, one
      from Brazil, one from Spain, and one from Italy. Results demonstrated that,
      provided the dosage form disintegrates, amounts dissolved range from 50 to 90% of
      the labeled value. Products were analyzed by high performance liquid
      chromatography (HPLC) and UV spectrophotometry.

PMID- 11291207
TI  - Analyzing current practice patterns: lessons from Amgen's Project ChemoInsight.
AB  - PURPOSE/OBJECTIVES: To retrospectively review data on chemotherapy dose/dose
      intensity in patients with breast cancer. DATA SOURCES: Computerized database,
      published articles, and book chapter. DATA SYNTHESIS: Chart reviews were
      conducted of 20,106 patients with breast cancer from 1,135 oncology practices
      throughout the United States. More dose delays, dose reductions, and suboptimal
      dose intensity occur in patients who are 65 years of age or older. Overall, dose
      intensity was not achieved in 18.4% of patients, dose reductions occurred in
      25.7% of patients, and dose delays occurred in 43.1% of patients. Neutropenia was
      often the cause of dose delays/reductions. CONCLUSIONS: A substantial number of
      patients with breast cancer experience chemotherapy dose delays or reductions.
      IMPLICATIONS FOR NURSING PRACTICE: Guidelines may help consistently manage
      primary and secondary prophylaxis of neutropenia. Nurses' can influence patients'
      attitudes about prescribed therapies.

PMID- 11291208
TI  - Advocating for quality cancer care: making evidence-based practice a reality.
AB  - PURPOSE/OBJECTIVES: To highlight oncology nurses as innovators who evaluate
      published data, develop new skills, and incorporate current knowledge into
      practice. DATA SOURCES: Published articles and book chapters. DATA SYNTHESIS:
      Established methods of synthesizing knowledge that can be used to evaluate data
      and identify areas of innovation. Oncology nurses can influence the adoption of
      new ideas into their practice. As healthcare evolves, oncology nurses need to
      adapt and refine their skills. CONCLUSIONS: Oncology nurses and oncology
      practices will need to demonstrate their value in the future healthcare paradigm.
      Oncology nurses must think more broadly about their roles. IMPLICATIONS FOR
      NURSING PRACTICE: Nurses should incorporate evidence-based techniques into their
      practice. Oncology nurses should identify and begin obtaining the skills needed
      to continue offering high-quality patient care as healthcare systems evolve.

PMID- 11291209
TI  - Chemotherapy dose and dose intensity: analyzing data to guide therapeutic
      decisions.
AB  - PURPOSE/OBJECTIVES: To provide key examples from the oncology literature related
      to chemotherapy dose/dose intensity to guide nurses in evidence-based decision
      making. DATA SOURCES: Published articles and abstracts of scientific findings and
      clinical trials. DATA SYNTHESIS: Understanding tumor biology and growth kinetics
      is essential in determining optimal approaches to cancer treatment and goal
      setting in cancer care. CONCLUSIONS: Therapeutic decision making ideally should
      be data driven. Dose and dose intensity can make a difference in therapeutic
      outcomes. Additional research with well-designed clinical trials, incorporating
      recent advances in cancer biology, is needed to define more distinctly the role
      of dose/dose intensity related to specific tumor types. IMPLICATIONS FOR NURSING
      PRACTICE: Establish therapeutic goals at initiation of therapy, and communicate
      them clearly with patients, families, and the rest of the healthcare team.

PMID- 11291210
TI  - How to prepare for an OSHA inspection.

PMID- 11291211
TI  - Get ready for a crackdown on federal overtime, child labor and minimum wage
      rules.

PMID- 11291212
TI  - Do you know what consumers can find out about your facility?

PMID- 11291213
TI  - AMDA (American Medical Directors Association) issues how-to guide for protocols
      on long-term care resident assessment.

PMID- 11291214
TI  - Things you can do to protect your facility against lawsuits. Part II: Avoiding
      operational risks.

PMID- 11291215
TI  - Controversial OSHA ergonomics standard goes into effect in January.

PMID- 11291216
TI  - Physician executives straddle the digital divide.
AB  - e-Health is here to stay and experts predict that the Internet will become the
      hub of health care. Rapid advancements in biotechnology and medical research,
      increasingly curious patients who surf the Internet for medical information, and
      pressures from managed care companies to contain costs and speed treatments are
      the central components driving e-health. Despite physician reluctance to embrace
      the e-revolution, many hospitals and medical groups are employing the Internet
      and information technology to improve their customer interface, as well as to
      reduce business costs. This article offers seven e-strategies for health care
      performance improvement: (1) Supply chain management; (2) e-transactions; (3)
      care management; (4) improving quality; (5) boosting revenues; (6) outsourcing;
      and (7) provider networks (Intranets). By helping to incorporate these key e
      solutions, physician executives can position their organizations for success in
      the new millennium.

PMID- 11291217
TI  - MedDigital trends and tactics to lead into the future.
AB  - Physician executives need to harness appropriate digital technology by
      understanding key trends and implementing best tactics. Being and doing
      MedDigital means taking back control and improving care--and, at the same time,
      improving efficiencies and the bottom line. This article presents seven e-trends
      that are shaping health care: (1) Consumers and patients are pushing doctors to
      go digital; (2) from Web health information to MedDigital decision support; (3)
      beyond managed care to custom health; (4) wireless is the way of the new world;
      (5) Passive web portals yield to digital destinations; (6) e-commerce means lower
      transaction cost; and (7) develop e-health care ROI methodologies and track
      results. The authors provide myriad examples of new technology that will
      revolutionize health care and provide both physicians and consumers with valuable
      interactive tools to enhance health, treatment, and decision-making.

PMID- 11291218
TI  - Physician behavior at the e-technology/learning intersection: an interview with
      Elliott Masie. Interview by Richard L. Reece.
AB  - Richard L. Reece, MD, interviewed Elliott Masie on January 16, 2001, to talk
      about the Internet learning world--that vast intersection of e-technology,
      learning, and human behavior. He describes how he looks beyond the hype of
      technology into how human beings behave and what they crave in social
      experiences. The real question, he says, is how do we have knowledge experiences
      and blend them with social experiences to achieve the optimal mix? Masie
      emphasizes, "The magic of learning is in the mix--what happens online and then
      what happens informally when we have a cup of coffee with a colleague." He
      continues, "Many of the capital market folks hate to hear about the human
      element, because they want to believe we'll be able to do everything from our
      PCs. But that's not how humans behave. It's the mixture that gets results. That's
      where the real excitement occurs."

PMID- 11291219
TI  - Get real: what will draw physicians to the Web?
AB  - What are physicians waiting for? What will it take to stimulate widespread
      adoption of Internet medical systems? How can health care leaders and physicians
      help the technology innovators and the executives of technology firms understand
      the components necessary to assure physician acceptance and utilization of new
      tools? (1) Don't underestimate the personal nature of a physician's practice. It
      really isn't a "business." (2) Most physicians are not Luddites; they are just
      extremely pragmatic and practical. (3) For the majority of physicians to adopt a
      new technology in their private office practice, it must address three major
      issues: money, hassle, and patient care. There are many obstacles to adopting the
      new technologies that are the result of physician training and expectations and
      the current models of payment and revenue generation. Some technological
      innovations are presented to physicians without sufficient respect for their
      knowledge of how medical practices really work. The benefits promised often don't
      match with the needs structure of the physicians. As a consequence, the cycle of
      diffusion of these new systems is extended and delayed.

PMID- 11291220
TI  - The two-edged sword: how technology shapes medical practice.
AB  - Technology is assuming an increasingly important role in medical practice and
      health care delivery, fueled by forces such as uncertainty, variability, error,
      and quality problems. While the benefits of technology are obvious, there are
      insidious costs that are harder to discern. Technology has a significant, but
      less appreciated, role in imposing standards and constraints upon medicine. These
      ancillary effects account for some of the physician reluctance to embrace
      technological innovations perceived as controlling. This article explores
      technology's wide-ranging effects in shaping medical care delivery. Technology is
      not a passive servant of the health care delivery system, but rather acts as a
      catalyst and shaper of that system. In the process of becoming more
      technological, medicine has been transformed from a profession with unmatched
      sovereignty into an industry shaped by technology amidst a context of social and
      political forces.

PMID- 11291221
TI  - 'Second generation' Internet e-health: the gladiator for HIPAA compliance?
AB  - The Health Insurance Portability and Accountability Act (HIPAA) is intended to
      simplify administrative processes and improve health information security. There
      are a number of traditional ways to address the expense and complexities of
      simplification, but none of them are bargains or beauties to behold: (1) Do-it
      yourself encryption; (2) new back-end system purchases; (3) legacy system re
      programming; or (4) onerous paper documentation. The good news is that 'second
      generation' e-health solutions are emerging that act as internal "wrappers" for
      health plan or provider data systems. They provide both an interface for end
      users and a layer of security for organizational information and allow detailed
      patient-related data to remain at the system owner's physical location. These
      second generation solutions don't just 'connect,' data, they actually
      'understand' the information, and can use data elements to invoke necessary
      rules, processing pathways, or personalization for specific stakeholders as
      required by HIPAA.

PMID- 11291222
TI  - A revolution in genetics: changing medicine, changing lives.
AB  - The sequencing of the human genome is only the tip of the iceberg. It is the
      beginning of a revolution that many predict will transform medicine. How will
      genetics research affect physicians and patients and the practice of medicine?
      When investigators identify the function and association of human genes with
      common chronic diseases, diagnosis, treatment, and classification of human
      diseases will be changed forever. Genetic susceptibility testing allows patients
      to know their predisposition to disease long before symptoms appear. Physicians
      can intervene with customized advice so that the patient can prevent, modify, or
      avoid the predisposed condition by better understanding both his or her genetic
      and environmental risk for disease. The promise of a genetic approach to drug
      therapy involves moving from one size fits all to personalized medicine tailored
      to the individual patient. Physicians will become mentors and counselors,
      advising patients on the best treatment path given their unique genetic
      predisposition--even in this sophisticated, high tech field, the physician
      patient relationship is likely to improve, highlighted by individualized
      therapies and personal attention.

PMID- 11291223
TI  - Our doctors are joining a labor union!
AB  - Are physicians going to join a union at your hospital, multi-specialty group, or
      HMO? Having recently lived through such an experience, the author shares the
      lessons that he has learned. This article outlines what physician executives need
      to do to prepare for the increasingly likely eventuality of physicians at their
      hospitals making a push for unionization. The best way to avoid a union is to
      manage people fairly, communicate with them constantly, and develop consensus for
      difficult decisions whenever possible. But if a petition lands on your desk, it
      is crucial to understand the laws governing union campaigns and the possible
      outcomes. From how to respond to a petition to election campaign strategies to
      the negotiation phase, physician executives need to be prepared for the very real
      possibility of physicians at their organizations deciding to unionize.

PMID- 11291224
TI  - Welcome everything.
AB  - The failure of management is largely a failure to bring our whole selves to it.
      What parts of your self do you bring to your work? Do you bring only the
      management mind, only logic, only the company guidelines? Or do you bring your
      passions, your values, your soul, your deepest self? Do you react? Or do you
      respond? Letting go of what you think you know can be the first step to a
      creative and powerful response. Many of the tools we use in management can
      actually remove us from the experience and make it harder to respond. Reacting
      closes down options. Responding opens up possibilities and nurtures trust. This
      is kindness transformed into a business imperative--responsiveness.

PMID- 11291225
TI  - The good leader.
AB  - What are the traits of successful leaders and can they be applied to those of us
      in health care? Leaders must deal with conflict to get a group of people to move
      in the same direction. Successful leaders learn to have difficult conversations
      that increase understanding and morale and creatively deal with the inevitable
      interpersonal conflicts present in every organization made up of people. Another
      useful trait for a leader during uncertain and chaotic times is the ability to
      see things as they really are, rather than as we wish or believe them to be.
      Successful leaders are also usually optimists who level with their co-workers.

PMID- 11291226
TI  - Someone promised mentors: will you deliver?
AB  - What are recruiters promising? Many new hires say that they accepted a job
      because of a promised mentoring program--one that never materializes, and one
      that the manager doesn't know was part of the discussions. Where does that leave
      the manager who may not be aware of this expectation? Faced with anchoring mobile
      Gen Xers, organizations are exploring mentoring as an inexpensive way to improve
      retention. But mentoring is not a technique that can be applied like a warm
      blanket to solve the problems of orientation, training, skills development, and
      retention. There are two reasons why mentoring isn't foolproof--the mentor and
      the protege. If you are considering a mentoring program, or becoming a mentor
      yourself, here are some points to ponder: (1) If you can't (or won't) do it, give
      convincing reasons up front; (2) establish the rules of engagement; (3) a
      mentoring relationship doesn't guarantee loyalty; (4) having a protege has
      political risks; (5) you can't force anyone to take advice; and (6) expect a quid
      pro quo.

PMID- 11291228
TI  - What is it like to work for a pharmaceutical company? Interview by Barbara J.
      Linney.
AB  - Is working for a pharmaceutical company a career option you've thought about
      pursuing? In this column, Barbara Linney interviews physician executive Edward A.
      Kaufman, MD, about his 20-year experience working in the pharmaceutical industry.
      He talks about how he held a series of jobs for SmithKline Beecham's clinical
      labs business and lived in a number of places. He describes his background and
      how it made him an attractive candidate for the position, why he sought out the
      pharmaceutical industry, the nature of the work, and some of the projects that he
      has been involved in. He gives examples of physicians who have joined the
      executive ranks at GlaxoSmithKline and what made them such high-caliber
      candidates for top leadership positions.

PMID- 11291227
TI  - Leading beyond the bottom line, Part 4. The questions it has raised.
AB  - The Leading Beyond the Bottom Line article series has received an overwhelming
      response from ACPE members, mostly in enthusiastic support of this new leadership
      concept. Some of the important questions raised by members are presented with
      answers from the authors. This article also explores the moral challenge of
      leadership and why health care is more than a business. In recent years, there's
      been confusion about the role of the health care enterprise, its leadership and
      its management. We have lost our way about the "moral" thing, the "right" thing,
      because we have no philosophy to guide us. To manage or lead in this "business"
      of health care, a philosophy is required that recognizes the multiple elements to
      which the leader has responsibility and obligations: the customers, community,
      employees, and, certainly, the financial assets.

PMID- 11291229
TI  - Common denominators of success.
AB  - There is no mystery to the success stories described in this column. In addition
      to a lot of hard work, a few basic principles have been applied to widely
      differing scenarios. These common denominators provide the philosophies and
      dynamics that can lead to your breakthroughs in quality health care delivery: (1)
      Trust--among the physicians and then between them and management and the board of
      directors; (2) positive physician culture and attitudes; (3) effective physician
      leadership; (4) patient care focus; (5) strong team orientation; and (6) true
      accountability by all stakeholders. Your job is to help your physicians feel they
      are major stakeholders in your health care delivery system and be their voice in
      clinical and financial decision-making at the highest level.

PMID- 11291230
TI  - Public health infrastructure: creating a solid foundation.
AB  - The nation's public health system remains in disarray, despite the 1988 warning
      by the Institute of Medicine in its landmark report, "The Future of Public
      Health." Recent concerns about antibiotic resistance, inadequate disease
      surveillance capabilities, bioterrorism, and an increasing need for training the
      public health workforce have brought this problem into the forefront of
      congressional concern. Recent legislation aimed at addressing this problem was
      passed last Fall and signed into law. This program will take a significant step
      towards ensuring a solid public health system when it is fully implemented.

PMID- 11291231
TI  - The new Stark rules: a kinder, gentler version?

PMID- 11291232
TI  - Gainsharing arrangements between hospitals and surgeon groups: an OIG Advisory
      Opinion.

PMID- 11291233
TI  - Drug- and chemical-induced cholestasis.
AB  - Cholestasis resulting from drugs is an increasingly recognized cause of liver
      disease. It produces a broad clinical-pathologic spectrum of injury that includes
      simple jaundice, cholestatic hepatitis, and bile duct injury that can mimic
      extrahepatic biliary obstruction, primary biliary cirrhosis, and sclerosing
      cholangitis. Although the risk of drug-induced cholestasis leading to a fatal
      outcome is quite rare, knowledge and recognition of the various forms of
      cholestatic injury assumes an importance whenever clinicians are confronted with
      jaundice or other manifestations of liver disease in patients receiving medicinal
      or chemical agents.

PMID- 11291234
TI  - Sepsis and cholestasis.
AB  - Sepsis-associated cholestasis should always be considered as part of the
      differential diagnosis of jaundice in the hospitalized or critically ill patient.
      The development of a disproportionate elevation of serum bilirubin in comparison
      with serum alkaline phosphatase and serum aminotransferases should be considered
      an early warning sign of an underlying infection, even in the absence of fever,
      leukocytosis, or other signs or symptoms. Prompt recognition and appropriate
      medical and surgical intervention may reduce morbidity and mortality.

PMID- 11291235
TI  - Postoperative jaundice.
AB  - Postoperative jaundice is often multifactorial (Fig. 2). A precipitating or
      causative factor may be identified but seldom can a specific therapy be offered.
      A systematic approach will help eliminate a hepatotoxic drug or identify a
      biliary tract problem. Treatment involves discontinuation of an offending drug;
      however, the drug, such as an anesthetic agent, may not be in use when the
      jaundice is detected. Recognition of an anesthetic-induced injury would certainly
      warn the physician not to repeat its use in future surgery for that patient.
      Hyperalimentation may contribute to jaundice, but patients developing
      postoperative jaundice are generally very ill and require nutrition. Extrahepatic
      biliary tract disease should be readily recognized and treated. The physician
      should be alert to the possibility of acalculous cholecystitis so that it can be
      appropriately diagnosed and treated.

PMID- 11291236
TI  - Total parenteral nutrition and cholestasis.
AB  - Hepatobiliary dysfunction is recognized as a major adverse effect of total
      parenteral nutrition (TPN). It is unknown if this is caused by a deficiency or
      toxicity of the TPN solution or the underlying pathophysiology of disease
      processes that require TPN therapy. This article presents algorithms for
      evaluating abnormal liver tests in patients on TPN and discusses treatment
      options and the current status of intestinal transplantation.

PMID- 11291237
TI  - Benign recurrent intrahepatic cholestasis.
AB  - Benign recurrent intrahepatic cholestasis is a rare autosomal recessive disorder
      characterized by repeated episodes of intense pruritus and jaundice. Each attack
      lasts from several weeks to months before resolving spontaneously. Patients are
      completely asymptomatic for months to years between symptomatic periods. The
      disorder does not lead to progressive liver disease. Although attacks seem to be
      associated with a viral prodrome, an inciting viral agent or toxin has not been
      defined. Genetic studies have mapped the defect of this disorder to the long arm
      of chromosome 18 and a gene that codes for a P-type ATPase, which appears to be
      involved in aminophospholipid transport. Therapy during symptomatic periods is
      supportive and aimed at relief of severe pruritus until the episode resolves
      spontaneously.

PMID- 11291238
TI  - Primary biliary cirrhosis and primary sclerosing cholangitis.
AB  - Primary biliary cirrhosis and primary sclerosing cholangitis are the most common
      chronic cholestatic liver diseases in adults that lead to biliary cirrhosis and
      its inherent complications such as portal hypertension and liver failure.
      Although important advances in the understanding of the pathogenesis of these
      conditions have been accomplished in the last two decades, much work is needed to
      uncover the interaction of genetic and immunologic mechanisms involved in their
      pathogenesis. Ursodeoxycholic acid at dosage of 13 to 15 mg/kg/d is the only
      agent that can currently be recommended in the treatment of PBC. No medical
      therapy aimed at disrupting disease progression is available for patients with
      primary sclerosing cholangitis, although several agents with different properties
      are currently under evaluation. Liver transplantation is the treatment of choice
      for patients with primary biliary cirrhosis and primary sclerosing cholangitis
      with end-stage liver disease.

PMID- 11291239
TI  - Autoimmune cholangiopathy.
AB  - Currently available evidence is insufficient to classify PBC and AIC as separate
      diseases. The ultimate answer to the question of whether AIC, defined as AMA
      negative PBC with ANA or SMA, is a disease distinct from AMA-positive PBC with or
      without ANA will require a detailed comparison of etiologic factors and
      pathogenetic mechanisms, once they are elucidated. It is intriguing to consider
      the suggestion of Heathcote that the term autoimmune cholangitis be adopted to
      describe PBC with or without detectable AMA. However, it is improbable that the
      venerable term PBC will be supplanted. Hepatologists will probably continue to
      use the terms AIC and AMA-negative PBC interchangeably, with little risk of being
      misunderstood.

PMID- 11291240
TI  - Cholestasis and alcoholic liver disease.
AB  - Histologic cholestasis and clinical jaundice may be seen in all stages of
      alcoholic liver disease. In rare cases, isolated cholestasis without significant
      steatosis, hepatitis, or cirrhosis is identified in an alcoholic patient. The
      mechanisms of ethanol-induced cholestasis are not well studied but may involve
      compression of intrahepatic biliary radicals or interference with basolateral
      uptake and intracellular transport of bile acids. In the evaluation of the
      jaundiced alcoholic patient, clinical, biochemical, and radiologic data are
      usually sufficient to distinguish alcohol-induced liver disease from extrahepatic
      biliary obstruction. In cases where the diagnosis is not readily apparent, more
      invasive studies such as liver biopsy or ERCP may be necessary. The risk of these
      invasive studies is directly related to the degree of underlying hepatic
      dysfunction.

PMID- 11291241
TI  - Intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy is one of the primary disorders of the
      liver that adversely affects maternal well-being and fetal outcome. Early
      identification of this condition, careful interdisciplinary monitoring, and
      prompt delivery at fetal maturity can improve outcomes in the mother and child.
      Although the cause is unclear, IHCP probably arises from a genetic predisposition
      for increased sensitivity to estrogens and progestogens and altered membrane
      composition and expression of bile ducts, hepatocytes, and canalicular transport
      systems. As a result, the elevations in maternal levels of bile acids and their
      molar ratios seen in healthy pregnancy rise further in IHCP patients. Also, as
      the normal fetal-to-maternal transfer of bile acids across the trophoblast is
      impaired, the excess bile acids with abnormal profiles accumulate and are toxic
      to the fetus. The management of IHCP is dictated by the increased risks of fetal
      distress, spontaneous preterm delivery, and sudden death, as well as by
      alleviating pruritus in the mother. These risks to the fetus rise progressively
      to delivery, regardless of serum levels of bile acids and ALT. Close monitoring
      of these markers is essential but does not prevent sudden fetal distress and
      death. Provision should be made to induce labor as soon as fetal lung maturity
      has been established. Ursodeoxycholic acid is the only therapy that has proven
      effective, albeit in small studies, in alleviating pruritus and restoring towards
      normal the abnormal profiles of bile acids and sulfated steroids in serum and
      other body fluids. Ursodeoxycholic acid seems to have no obvious adverse effects
      on the fetus, but experience is insufficient to draw conclusions regarding
      teratogenicity and prevention of adverse outcomes.

PMID- 11291242
TI  - Intrahepatic cholestasis following liver transplantation.
AB  - Intrahepatic cholestasis following liver transplantation commonly occurs after
      liver transplantation and may be caused by infections, drugs such as cyclosporine
      and sulfonamides, and acute or chronic rejection. Less common causes such as
      fibrosing cholestatic hepatitis or recurrent primary biliary cirrhosis or primary
      sclerosing cholangitis may also be encountered. Biliary strictures may also be
      present. Although some disorders may be managed medically, others often require
      repeat liver transplantation. Prompt recognition and specific treatment can
      improve the outcome for liver transplant recipients.

PMID- 11291243
TI  - Cholestasis after hematopoietic cell transplantation.
AB  - Cholestasis and jaundice are common after hematopoietic cell transplantation and
      may have multiple causes. Specific disorders that may contribute to cholestasis
      in this setting include sepsis, hemolysis, cyclosporine administration, drug
      toxicity, parenteral nutrition, graft versus host disease, viral infection, and
      extrahepatic obstruction.

PMID- 11291244
TI  - Cholangiopathy in HIV-infected patients.
AB  - HIV cholangiopathy is a disease of advanced-stage AIDS that presents with biliary
      symptoms and anicteric cholestasis. An abnormal ultrasound examination in a
      patient with low CD4 count is evaluated by endoscopic retrograde
      cholangiopancreatography, which demonstrates the characteristic cholangiographic
      abnormalities. Besides being the gold standard for diagnosis, it offers
      therapeutic intervention and possible pain relief in the presence of papillary
      stenosis. An infectious pathogen is identifiable in a majority of patients,
      suggesting infection-related damage to the biliary tree. Anti-infective therapy,
      however, usually is ineffective, and prognosis is related to the underlying stage
      of AIDS.

PMID- 11291245
TI  - Genes and ageing: beyond good and evil in the senescent cell.

PMID- 11291246
TI  - The molecular biology of hepatitis C virus. Genotypes and quasispecies.
AB  - Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide.
      HCV is a positive-strand genotype RNA virus with extensive genetic heterogeneity;
      HCV isolates define 6 major genotypes, and HCV circulates within an infected
      individual as a number of closely related but distinct species, termed a
      quasispecies. This article reviews characteristic aspects of HCV molecular
      biology and their implications for treatment and vaccine development.

PMID- 11291247
TI  - Clinical use of hepatitis C virus tests for diagnosis and monitoring during
      therapy.
AB  - This article reviewed various methods used for the diagnosis and monitoring of
      HCV infection and discusses potential clinical applications. Substantial
      improvements have recently been made in assay technology. Moreover, the role of
      molecular testing in the clinical setting of hepatitis C is becoming better
      defined. The major challenge facing clinical laboratories is the further
      refinement, implementation, and standardization of optimized molecular tests, so
      that reliable data may be made available to clinicians. In turn, clinicians must
      understand the limitations of each methodology, including the variability of
      testing that may occur among different laboratories. As more experience is
      gathered, molecular testing will probably provide important data regarding the
      most effective use of current and future therapies for individual patients to
      achieve maximum benefit in the management of hepatitis C.

PMID- 11291248
TI  - Factors contributing to the evolution and outcome of cirrhosis in hepatitis C.
AB  - A number of factors are important in the evolution of chronic hepatitis C to
      cirrhosis. These include the length of time that the patient has been infected,
      the age at exposure, dual infection with other viruses, alcohol use, and
      genotypes, especially in liver transplant recipients. The diagnosis of cirrhosis
      is made by clinical assessment of the patient, the use of imaging studies, a
      thoughtful laboratory evaluation, and histologic examination of liver tissue.

PMID- 11291249
TI  - Overview of interferon therapy for chronic hepatitis C.
AB  - The future therapy for chronic hepatitis C will probably include measures to
      decrease hepatocellular injury along with multidrug combinations, including
      inhibitors of the hepatitis C viral protease, helicase, or polymerase to reduce
      serum levels or eradicate HCV RNA. The results of recently concluded trials of
      IFN-alpha 2b plus ribavirin combination therapy have shown a twofold improvement
      in the biochemical and virologic response rates and superiority by other measures
      of efficacy with an acceptable safety profile. In view of these results, new
      guidelines for the management of chronic HCV infection are appropriate (Fig. 1).

PMID- 11291250
TI  - Predictors of a favorable response to alpha interferon therapy for hepatitis C.
AB  - The most consistently identified predictive factors for a response to both IFN
      alpha monotherapy and IFN-alpha in combination with ribavirin are a low HCV RNA
      level, the absence of fibrosis, infection with HCV genotype 2 and 3, and a
      prolonged duration of treatment. In addition, an early response to IFN-alpha
      predicts response to IFN-alpha monotherapy but not necessarily to combination
      therapy. There does not appear to be any major gain in treating IFN-naive
      patients with HCV genotype 2 or 3 infection with a combination of IFN-alpha and
      ribavirin for longer than 6 months. The identification of these predictive
      factors has allowed improvement in study design and assessment and may provide a
      patient with an idea of the likelihood of response, making possible a more
      informed decision regarding treatment. At present, none of these factors, either
      alone or in combination, completely predicts response to IFN-alpha. Thus,
      individual patients should not be denied treatment on the basis of these factors.

PMID- 11291251
TI  - Hepatitis C viral dynamics.
AB  - It is apparent that the sooner the virus is cleared from the serum following IFN
      monotherapy, the better the sustained virologic response rates. It is also clear
      that in patients infected with HCV genotype 1a and 1b, standard dosages of IFN
      alpha 2b (3 MU) administered three times a week are inadequate for a substantial
      and sustained lowering of HCV RNA serum levels. Understanding the kinetics and
      dynamics of HIV and HBV has greatly improved the understanding of the life cycle
      of these viruses and their response to therapy. Studies of the kinetics of HCV
      following initiation of IFN monotherapy have revealed that IFN-alpha 2b causes a
      rapid dose-dependent (3 < 5 < 10 = 15 MU) reduction in HCV RNA levels within 24
      to 48 hours. This rapid exponential decline in RNA levels is best explained by an
      effect of IFN on viral production or release. The dose of other IFN products that
      maximally suppresses viral levels needs to be determined. Mathematical
      calculations reveal that HCV has a serum half-life of 3 hours and a viral
      production rate of 1.0 x 10(12) virions/d. After this rapid decline, there is a
      slower phase of viral decline that varies widely among patients and is attributed
      to the death rate of infected liver cells. The rate of decline of the second
      phase, which is probably mediated by immune clearance of infected liver cells, is
      the best viral kinetic predictor of early viral clearance. This kinetic
      information indicates that in patients infected with HCV genotype 1a or 1b,
      initial therapy with IFN should be daily and initial doses should be sufficient
      to reduce viral levels by more than 95% within 48 hours. Whether higher doses of
      IFN will alter or enhance the second phase of viral decline needs to be
      investigated. Also, the effect of ribavirin on IFN-mediated changes in HCV RNA
      levels needs to be investigated in carefully performed kinetics studies to better
      determine its mechanism of action. Defining the viral kinetics in patients
      infected with HCV genotype 2 or 3 and in patients who do not respond to IFN
      therapy will also improve the approach to therapy.

PMID- 11291252
TI  - Combination treatment with interferon and ribavirin for chronic hepatitis C.
AB  - Interferon was the first drug shown to be effective in patients with chronic
      hepatitis C, but initial treatment regimens achieved sustained loss of virus in
      only a small minority of patients. The combination of IFN with ribavirin now
      makes sustained response rates of 30% to 40% possible. This is quite a remarkable
      achievement for a pharmacologic treatment of a chronic viral infection. It is now
      reasonable to assume that early treatment and eradication of chronic hepatitis C
      might reduce the growing burden of hepatitis C and its complications on the
      healthcare system. Future researchers will strive to optimize combination
      treatment regimens. Longer treatment courses and intensified induction regimens
      using either daily dosing, high doses, or both may improve long-term response,
      but this remains speculative. Other forms of IFN may improve response or increase
      the ease of drug administration. Conjugation of biologic compounds to
      polyethylene glycol can result in significant prolongation of plasma half-life
      while maintaining the properties of the parent molecule. Some biologic properties
      may be altered, however, so pegylated IFN must continue to be evaluated in
      clinical trials. There is limited clinical data on other recombinant or natural
      interferons in combination with oral ribavirin, however, these may prove to be
      equally effective. Combinations of IFN with one or more other antiviral, anti
      inflammatory, or immune modulatory agents will need to be studied. Although
      amantidine is not effective against hepatitis C as a single agent or in
      combination with IFN, the combination of IFN, ribavirin, and rimantidine has been
      shown to have antiviral activity superior to the IFN-ribavirin combination
      against influenza virus and possibly against HCV.

PMID- 11291253
TI  - Cost-effectiveness of combined interferon and ribavirin versus interferon alone.
AB  - Several decision analysis, computer-generated models developed to study the cost
      effectiveness of current treatment for chronic hepatitis C appear to have
      produced similar results. They indicate that IFN monotherapy and the combination
      of IFN plus ribavirin treatment have calculated cost-effectiveness ratios that
      either fall within the bounds of other widely accepted current therapies in
      medicine or are cost-saving. This cost effectiveness has been shown for the
      treatment of previously untreated patients, for the re-treatment of patients who
      experience relapse after an initial course of IFN monotherapy, and for the re
      treatment of those patients who did not respond to IFN monotherapy. Although
      targeting treatment to patients most likely to respond will improve cost
      effectiveness, the benefits of treatment are such that even empiric IFN
      monotherapy, without liver biopsy, HCV RNA quantitation, or HCV genotyping, has
      an acceptable cost effectiveness. Although not studied, empiric combination
      therapy might result in even further cost efficiencies.

PMID- 11291254
TI  - Treatment of hepatitis C patients with normal aminotransferases levels.
AB  - An important subset of patients with chronic hepatitis C have normal ALT levels
      despite having detectable HCV RNA in serum. These patients are typically
      identified after donating blood and being found positive for antibody to HCV
      (anti-HCV). A strict definition of this patient population is needed, which
      should include the presence of anti-HCV, detectable HCV RNA by PCR and
      persistently normal ALT levels. These patients are usually asymptomatic, but on
      liver biopsy almost all have histologic evidence of chronic hepatitis. The
      histologic findings generally are mild, and cirrhosis is rare. The long-term
      outcome of this group of patients with chronic HCV infection is not known, but
      the prognosis is probably good. In small, uncontrolled trials of IFN-alpha in
      patients with normal ALT levels, end-of-treatment virologic responses occurred in
      42% of patients, and sustained responses 6 to 12 months afterwards in 13% of
      patients. These rates of response are not very different from those reported in
      patients with elevated ALT levels. Importantly, in most studies, serum ALT levels
      became elevated during IFN therapy in approximately one half of patients, and
      levels remained elevated in some of these patients after therapy. These findings
      suggest that IFN-alpha therapy is not usually beneficial and may be harmful in
      chronic hepatitis C patients with normal ALT levels. Combination therapy with IFN
      and ribavirin has not been evaluated in this group of patients.

PMID- 11291255
TI  - Treatment of chronic hepatitis C in pediatric patients.
AB  - Although HCV infection in children shares some clinical features with that in
      adults, it is clearly different in several ways. These differences may have
      important implications for treatment. Some differences, such as milder disease,
      less frequent extrahepatic manifestations, and fewer comorbid conditions causing
      progression, argue against aggressive treatment in childhood. Other factors, such
      as less severe liver disease, shorter disease duration, possibly higher rates of
      sustained virologic response, and better tolerance of IFN, may be reasons to
      pursue treatment before advanced hepatic injury occurs. Given the relatively
      small number of pediatric patients with HCV infection and the gaps in the current
      understanding of natural history and effects of therapy in these patients,
      treatment should be undertaken only in clinical trials, so that careful data
      collection and monitoring can define more precisely the safety and efficacy of
      IFN therapy in children.

PMID- 11291256
TI  - Effect of interferon therapy on the natural history of hepatitis C virus-related
      cirrhosis and hepatocellular carcinoma.
AB  - In patients with chronic hepatitis C who have a sustained virologic response to
      IFN therapy, there is a dramatic effect on the natural history of the disease,
      with ALT levels becoming normal, histologic activity improving or disappearing,
      and the progression of fibrosis slowing. A sustained virologic response 6 months
      after the end of treatment is predictive of a sustained remission 4 years later.
      From these results, a long-term survival benefit is expected from IFN treatment
      in patients with an intermediate or rapid rate of fibrosis. For patients with
      chronic hepatitis C who do not experience a sustained eradication of virus, there
      is evidence that IFN treatment significantly reduces the viral load and serum ALT
      level, improves histologic activity, and blocks fibrosis progression, in
      comparison with the natural history of this disease. Therefore, patients who
      still have a detectable level of HCV RNA should no longer be considered
      nonresponders to IFN therapy. Although the number of randomized trials is
      [figure: see text] small, cumulative data suggest that IFN therapy can reduce the
      incidence of and the mortality from hepatocellular carcinoma in patients with
      cirrhosis.

PMID- 11291257
TI  - Treatment strategies for recurrent hepatitis C after liver transplantation.
AB  - Chronic hepatitis C is a common indication for liver transplantation, accounting
      for 25% to 50% of all transplantation candidates in most transplant centers.
      Despite uncertainties regarding rates of disease progression after
      transplantation, a consensus is emerging that recurrent HCV infection results in
      liver failure in a significant although currently unmeasured proportion of
      patients, and that the period over which this progression occurs is shorter than
      in the immunocompetent population. As the disease process moves into its second
      decade after transplantation it can be anticipated that future morbidity and
      liver-related mortality will increase. Whether disease progression is accelerated
      by definable factors is not yet fully established, but HCV RNA levels before or
      soon after transplantation and aggressive immunosuppressive measures appear to
      influence the post-transplantation outcome. Strategies to prevent or to reduce
      the effect of HCV infection after liver transplantation are therefore essential.
      The ability to intervene in this disease is currently limited. The main obstacles
      are the difficulty in predicting the outcome in the individual patient and the
      lack of effective therapy. In contrast with hepatitis B, in which hepatitis B
      immune globulin has improved survival, there are no therapeutic strategies to
      prevent recurrent HCV infection. Neither IFN nor ribavirin, when administered as
      a single agent, results in sustained viral clearance. However, administration of
      both drugs in combination, either to prevent disease or to treat recurrence,
      appears promising. The inability of currently available antiviral therapy to
      eliminate HCV in the setting of liver transplantation suggests that indefinite
      treatment designed to suppress viral replication will be necessary. The
      feasibility of such an approach will depend on the development of drugs that
      reduce the histologic activity of hepatitis, improve graft and patient survival,
      and have side effect profiles that are acceptable to patients.

PMID- 11291258
TI  - Prospects for a hepatitis C virus vaccine.
AB  - The scientific and clinical challenges that must be addressed and overcome in
      developing an efficacious HCV vaccine are substantial but not insurmountable. In
      a short period, considerable progress has been made in the understanding of HCV
      pathogenesis, epidemiology, and immunology, and the field of vaccinology in
      general is making very significant strides in developing new ways to activate and
      modulate immune responses. Advances in DNA vaccines, novel adjuvants, and
      recombinant protein technology may be keys in developing creative strategies to
      generate protective immunity against HCV.

PMID- 11291259
TI  - A trauma-informed approach to screening and assessment.
AB  - Universal trauma screening and specific trauma assessment methods are necessary
      to developing collaborative relationships with trauma survivors and offering
      appropriate services.

PMID- 11291260
TI  - Envisioning a trauma-informed service system: a vital paradigm shift.
AB  - With the recognition that large numbers of men and women receiving services in
      the mental health and addictions systems are the survivors of sexual and physical
      abuse, practitioners need to become informed about the dynamics and the aftermath
      of trauma.

PMID- 11291261
TI  - Trauma-informed inpatient services.
AB  - Inpatient hospitalizations can be difficult for the survivors of sexual and
      physical abuse unless practitioners take care to make the hospital stay trauma
      informed.

PMID- 11291262
TI  - Trauma-informed approaches to housing.
AB  - Supportive housing providers can play a vital role in the recovery of persons
      exposed to abuse and violence. Specific modifications for delivering housing
      support services are recommended based on an emerging trauma-informed
      perspective.

PMID- 11291263
TI  - Designing trauma-informed addictions services.
AB  - Because addictive disorders are so common among women who have experienced
      prolonged sexual and physical abuse, it is especially important to design
      addictions services that meet the needs of the trauma survivor.

PMID- 11291264
TI  - Trauma-informed services and case management.
AB  - The development of trauma-informed services challenges providers to think about
      the values and practice of case management in a new way.

PMID- 11291265
TI  - Defining the role of consumer-survivors in trauma-informed systems.
AB  - This chapter provides pragmatic recommendations for creating partnerships with
      recipients of services who have traditionally been the most silent stakeholders
      in mental health system design and service delivery.

PMID- 11291266
TI  - Care of the clinician.
AB  - Effective services for trauma survivors rely on addressing the support and care
      needs of clinicians and administrators.

PMID- 11291267
TI  - [Gluten enteropathy in Croatian children is primarily associated with the HLA-DR3
      DQ2 haplotype].
AB  - OBJECTIVES: Coeliac disease (CD) has one of the strongest class II HLA
      association of any human disease. The goal of this study was to establish the
      frequency of HLA-DR and DQ antigens, as well as common HLA-DR-DQ haplotypes among
      CD patients. No similar study has previously been done in Croatian patients.
      PATIENTS AND CONTROLS: There were 58 biopsy proven patients with CD. The control
      groups comprised 502 and 118 healthy person for HLA-DR and HLA-DQ typing,
      respectively. METHODS: The class II HLA-DR and DQ antigens typing were carried
      out by standard microcytotoxicity assay for B cells. Only antisera to three
      specificities (DQ1, 2 and 3) were available to us at the time of the study.
      RESULTS: We confirmed the high frequency of HLA-DR3 (84.48%; RR = 23.7; p <
      0.00001) in our patients with CD. As reported in other populations, most of the
      patients negative for DR3, were heterozygous for DR7 and DR5 (10.34%) or DR4/DR5,
      DR4/DR6 (3.44%). CD was significantly correlated with the presence of HLA-DQ2
      (96.55%, RR = 75.9; p < 0.00001). Correlation with CD was strongly dependent on
      homozygosity, 15 out of 58 (25.86%) of the patients and 4 (2.87%) of the controls
      being homozygotes for DQ2 (RR = 11.9; p < 0.00001). The remaining two patients
      were DR4-DQ3 positive. Among extended haplotypes only DR2-DQ1 was under
      represented (RR = 0.3; p < 0.0033). CONCLUSION: The results suggest that in
      Croatia CD is primarily associated with HLA-DQ2 specificities on the DR3-DQ2
      haplotype.

PMID- 11291268
TI  - [Presence of Chlamydia pneumoniae antibodies in patients with ischemic heart
      disease and acute myocardial infarct].
AB  - Numerous seroepidemiological studies that suggest an association of C. pneumoniae
      infection and atherosclerosis have been published in last decade. The aim of this
      study was to assess a prevalence of C. pneumoniae antibodies in population of
      Zagreb area, and to investigate possible differences in prevalence of antibodies
      in patients with atherosclerosis and healthy controls. Forty-seven patients with
      coronary artery disease or myocardial infarction and 54 controls without any
      previous history of atherosclerosis were enrolled in the study. Sera were
      examined by microimmunofluorescence test. Persons with IgA antibody titers > or =
      1:32, and/or IgG antibody titers > or = 1:64 were considered as seropositive. We
      found 75% seropositive in a total number of subjects, although number of
      seropositive and higher titers of antibodies were found more often in patients
      with atherosclerosis compared to control group: 74.5% of IgA seropositive
      patients versus 33.3% seropositive in control group, and 89.4% of IgG
      seropositive patients compared to 63% seropositive controls. Chronic (persistent)
      infections with C. pneumoniae were noted in 74.5% of patients and 33.3% controls.

PMID- 11291269
TI  - [Carcinoma of the urinary bladder resembling lymphoepithelioma].
AB  - Lymphoepithelioma-like carcinoma of the bladder is rare and has only recently
      been described at this site. We report a case of lymphoepithelioma-like carcinoma
      of the urinary bladder in a 70-years old male patient who presented with painless
      hematuria lasting for one month. The patient underwent transurethral resection
      two times. Histopathologic diagnosis was transitional cell carcinoma.
      Histopathologic examination of the third biopsy showed tumor tissue with typical
      syncitial growth pattern of atypical, large, epitheloid cells with ill-defined
      cytoplasmic borders, prominent nucleoli and numerous mitoses. A prominent
      lymphocytic infiltrate was found as a component of the tumor.
      Immunohistochemistry showed positive reaction for cytokeratin and epithelial
      membrane antigen, and negative results for leukocyte common antigen, CD3, CD20,
      CD30, CD68 and PSA. The lymphoid infiltrate was an admixture of T and B cells.
      The tumor invaded the muscle wall. After last surgery the patient underwent
      chemotherapy by local application of Adriablastine. At present the patient is
      without recurrence 10 months after the last surgery.

PMID- 11291270
TI  - [Pseudomyxoma peritonei associated with splenic mucinous epithelial cysts--case
      report].
AB  - A massive gelatinous ascites occurred in a 60-year-old patient, with no primary
      tumor found in the clinical work-up. The malignant cells were not found in the
      cytological examination of ascites. Explorative laparotomy revealed a gelatinous
      mass of 14 kg, a cystic tumor of the omentum and an identical cystic tumor of the
      spleen's lower pole. It was a well differentiated mucinous cystadenocarcinoma,
      most likely originating in the appendix. Most interesting is the involvement of
      the spleen with mucinous epithelial cysts, described as a rare finding associated
      with pseudomyxoma.

PMID- 11291271
TI  - [Drug therapy of hemorrhage in esophageal and gastric varices: role of vasoactive
      drugs].
AB  - Esophageal and gastric variceal bleeding is one of the most severe complications
      of portal hypertension and with high mortality. The aim of the therapy is to stop
      bleeding, replace the lost amount of blood and erythrocytes, treat coagulopathy,
      prevent rebleeding and improve liver function. Commonly accepted method to stop
      bleeding from varices is endoscopic hemostasis. Four vasoactive drugs, two
      natural peptides (vasopressin and somatostatin) and their analogues (terlipressin
      and octreotide) can control acute bleeding from gastric and esophageal varices.
      They lower portal pressure and the pressure in colateral circulation by
      vasoconstriction in splanchnic basin, and by inhibition the activity of
      endogenous vasodilatators. The high incidence of serious side-effects of
      vasopressin, even with nitroglycerin, has limited its application and decreased
      the use of this drug, with its abandonment in Europe. The vasopressin analogue,
      terlipressin, has a lower number of side-effects and is more effective in control
      of bleeding. Early terlipressin application at home, prior to hospital admission,
      diminishes mortality due to bleeding, thus attaching additional importance to
      this drug. Somatostatin, when applied as intravenous bolus injection, controls
      acute bleeding very efficiently and quickly. Five day somatostatin infusion after
      endoscopic hemostasis prevents rebleeding, with minimal side-effects. Octreotide
      is very efficient in long-term therapy of endocrine tumors due to its longer half
      life, better hormone inhibition, and simple application compared to somatostatin.
      Like somatostatin, it can also control variceal bleeding. It appears that the
      long-term subcutaneous octreotide application prevents rebleeding and improves
      liver function, all of which yields a new dimension to its use.

PMID- 11291272
TI  - [Radiotherapy treatment of lymphoma].
AB  - Radiotherapy and/or chemotherapy are primary treatment modalities in the therapy
      of lymphoma. The treatment depends on the lymphoma type, stage of disease and
      patients general condition. Radiation therapy is applied with curative or
      palliative intent, either as a single or combined modality treatment. In patients
      with stage I and stage IIA Hodgkin's lymphoma (HL) and no adverse risk factors,
      radiotherapy is applied as a single modality treatment. Moreover, treatment
      modalities in early-stage HL (I and IIA) consisting of either chemotherapy alone
      or combined with radiotherapy are the subject of ongoing clinical trials. In
      addition to the region/s with clinically involved lymph nodes, the target volume
      of radiation therapy applied as a primary radical treatment modality (stages I
      and IIA) also includes non-involved lymph nodes of adjacent regions aimed at
      their prophylactic irradiation. Such extended radiation fields are, for instance,
      the "mantle-field" and the "inverted-Y" field. On the other hand, with radiation
      therapy applied in combination with chemotherapy, the target volume depends on
      both the stage of the disease and the number of chemotherapy cycles. Likewise,
      the combined treatment is dependent on whether the role of radiotherapy is only
      the control of clinically involved regions, or of regions with potential
      subclinical disease too. Chemotherapy is the most frequently applied treatment
      modality in the management of non-Hodgkin's lymphoma (NHL). Radiation therapy as
      a single modality treatment with curative intent is applied in patients with,
      according to the histopathologic classification of the disease, the indolent NHL
      type and pathological stages I and II in continuation. The target radiation
      volume includes the clinically involved region, and possibly other adjacent
      clinically non-involved regions. In higher stages of disease or other, more
      aggressive NHL chemotherapy is applied either alone or in combination with
      adjuvant radiotherapy.

PMID- 11291273
TI  - [What a physician should know about zeolites].
AB  - Zeolites are natural and synthetic hydrated crystalline aluminosilicates endowed
      with absorptive and ion exchange properties. They have found numerous and
      multifarous applications--in industry as catalysts and absorbents, in water
      sanitation for the removal of ammonia and heavy metals, in agriculture as
      fertilizers, and in animal husbandry as the absorbents of excreted material and
      as food additives. Medical applications have included the use in filtration
      systems for anesthesia or dialysis and as the contrast materials in NMR imaging.
      Recently, zeolite powders for external use have found application as deodorants,
      antimycotic agents and wound dressings. Peroral use of encapsulated zeolite
      powders enriched with vitamins, oligoelements or other ingredients has been
      claimed to exert beneficial medical effects. Ingestion of zeolites may be
      considered analogous to the clay eating (geophagia), considered in traditional
      medicine as a remedy for various illnesses. Being amphoteric, zeolites are partly
      soluble in acid or alkaline media, but within the physiological pH range the
      solubility is generally low. Minimal amounts of free aluminium or silicium from
      the ingested zeolites are resorbed from the gut. The bulk of ingested zeolite
      probably remains undissolved in the gut. In view of the ion exchange properties,
      zeolites may be expected to change the ionic content, pH and buffering capacity
      of the gastrointestinal secretions and to affect the transport through the
      intestinal epithelium. In addition, zeolites could affect the bacterial flora and
      the resorption of bacterial products, vitamins and oligoelements. The contact of
      zeolite particles with gastrointestinal mucosa may elicit the secretion of
      cytokines with local and systemic actions. Reactive silicium ions might react
      with biomolecules of the intestinal epithelium, and if resorbed, do so in other
      cells. Mutagenic and carcinogenic effects of zeolite particles have been
      described, resembling such effects of asbestos fibers. Thus, local and systemic
      effects of zeolites may be complex and interrelated, and an objective assessment
      requires appropriate experimental models.

PMID- 11291274
TI  - [Committee for Human Rights and Medical Ethics of the Croatian Medical
      Association].
AB  - The historical development of ethical standards and institutions of Croatian
      Medical Association is presented. The first standards were "Medical order and
      Community" in 1895 and the ethical codex under the name "Main principles of
      Medical dignity" in 1901 resp. 1921. According to the new Association's Statute
      in 1990 the first "Committee on Human Rights and Medical Ethics" was founded.
      Since 1995 the Committee operates as a common "Committee on Medical Ethics and
      Deontology" of Croatian Medical Association and of Croatian Medical Chamber. In
      short the activities of committees in both periods, 1991-1995 and 1995-1999 are
      presented, including the establishing of a new "Codex of Medical Ethics". Since
      1999 the Croatian Medical Chamber divorced the cooperation with Croatian Medical
      Association and founded his own Committee. The Croatian Medical Association is
      now without ethical committee. The establishment of a new, common Committee of
      the Medical Association, Medical Chamber and Universities is suggested.

PMID- 11291275
TI  - [Three therapeutic recipes from the pages of the baptismal record book of the
      Kastel Parish in Istria].
AB  - In Croatian archives a rich collection of registers is preserved. Among the
      oldest and best-conserved collections of such valuable sources in Europe, are
      those from the territory of Istria. Investigating these sources we focused our
      attention on three recipes for treatment of calculi and cuts found on pages of
      Kastel baptismal's record (1749-1815) in Istria. Similar to other recipes found
      in various other recipe collections they mirror interlace of folk experience and
      theurgical views of healing which was detected unexpectedly sometimes on
      unconventional places, have survived on Croatian territory throughout centuries.

PMID- 11291276
TI  - [Spontaneous pneumomediastinum as a complication of asthma in children and
      adolescents].

PMID- 11291277
TI  - [Communicable diseases in Croatia].

PMID- 11291278
TI  - Evaluation of diastolic function: old and new methods.
AB  - Understanding and evaluation of diastolic function have changed with the
      development of new diagnosis methods. Careful attention to various aspects of
      diastolic function can provide valuable clinical information regarding the
      diagnosis for patient's heart failure, estimation of left ventricular filling
      pressures, optimal management strategy, and prognosis. With the advent of
      noninvasive hemodynamic methods, the evaluation of diastolic function can be
      performed routinely as a part of assessment of cardiac function.

PMID- 11291279
TI  - New technologies in stress echocardiography.
AB  - Stress echo has become the preferred theater where innovative technologies are
      first tested. The new technologies address, in different ways, various
      physiological targets: more quantitative assessment of the regional wall
      thickening (by anatomical M-mode); operator-independent assessment of global and
      regional systolic function (by anatomic boundary detection and color kinesis);
      tissue composition and physiologic state (by tissue characterization); transmural
      stratification of myocardial (subendocardial) function (by tissue Doppler
      imaging); more quantitative evaluation of contrast-enhanced myocardial perfusion
      (by harmonic imaging). All new emerging techniques aim to improve display and
      communication among physicians by translating the description of function into
      numbers and/or colors. However, cardiologists have to be aware that due the pro
      technology bias of modern medicine, we, as physicians, are encouraged to trust,
      to use (and to buy) technologies far before their clinical incremental value has
      been shown.

PMID- 11291280
TI  - Doppler tissue imaging.
AB  - This paper try to give a general overview of the main areas of DTI clinical
      application, its main technical limitations, new directions still under
      investigation and some potential future developments of this emerging imaging
      technique. In this review article we pretend to discuss the main aspects of the
      new DTI method, its present "state of the art" and future perspectives of
      scientific and technical development.

PMID- 11291281
TI  - Assessment of myocardial perfusion by contrast echocardiography.
AB  - Contrast echocardiography delineates myocardial perfusion and has the potential
      for quantitating coronary flow and assessing myocardial viability. These
      applications add important physiologic information to the anatomic information
      readily available from conventional echocardiography. Because it can be rapidly
      performed at the bedside, contrast echocardiography may be valuable tool for the
      use in acute myocardial ischemia. When contrast echocardiography has been used
      after recanalization of occluded coronary arteries, the assessment of myocardial
      salvage conveys information concerning reflow, stunning, and prognosis, and in
      the case of angioplasty it provides immediate information regarding the success
      of the procedure. Contrast echocardiography can also assess myocardial areas at
      risk of irreversible damage and the presence or absence of collateral flow.
      Myocardial contrast echocardiography is a rapidly changing field and with the
      continued development of newer contrast agents and refinement of ultrasound
      imaging equipment, the applications of contrast echocardiography will continue to
      grow.

PMID- 11291282
TI  - Dynamic three dimensional evaluation of intracardiac flow.
AB  - Three-dimensional color Doppler is a new technique that provides three
      dimensional images of intracardiac flow jets. Despite the different measurement
      methods available, noninvasive quantification of valve regulation is still
      controversial in some cases. It is also sometimes difficult to appreciate the
      spatial extension of the jet. Visualisation of regurgitant flows in three
      dimensions shows its complex shape, origin, direction and spatial distribution,
      and correlates accurately with regurgitant volume and regurgitant fraction by
      different methods (angiography, two-dimensional Doppler). Unnoticed its in the
      two-dimensional image have been detected with the three-dimensional image and
      additional qualitative information to the two dimensional image has been provided
      by this new technique in a high percentage of patients.

PMID- 11291283
TI  - Quantification of myocardial perfusion using contrast echocardiography:
      methodological basis of image postprocessing.
AB  - Intravenous contrast agents have provided the opportunity to clinically assess
      myocardial perfusion using ultrasound. In perfusion echocardiography, obtaining
      maximal diagnostic information requires the use of digital image postprocessing
      techniques, since subjective visual interpretation can be frequently inaccurate.
      Prior research using other intravascular tracers such as radioactive microspheres
      provides the theoretical basis for perfusion analysis that can be readily
      implemented to contrast echocardiography. Aspects of digital videodensitometric
      quantification, fitting to gamma-variable mathematical wash-in/wash-out functions
      and parameter analysis have been well validated for other tracers and have
      demonstrated excellent applicability in contrast echo. Currently available
      scanner technologies provide with a number of image-acquisition modalities, from
      standard continuous to intermittent-triggered images that require specific
      postprocessing algorithms. The present paper reviews the basis of temporal and
      spatial contrast postprocessing. The issues of image registration, background
      subtraction, videointensity measurement and mathematical function fitting are
      also discussed. This theoretical background should be helpful to understand the
      general aspects of currently available and future systems of perfusion
      densitometric systems.

PMID- 11291284
TI  - Current status of three-dimensional echocardiography.
AB  - Volume rendered three-dimensional echocardiography (3DE), a rapidly emerging
      imaging method, offers clinicians and surgeons a new perspective for visualizing
      the heart. Using both transthoracic and transesophageal approach this new
      methodology enables qualitative and quantitative information of cardiac disorders
      to be obtained. 3DE image projections have allowed visualization of intracardiac
      structures and great vessels and delineation of their pathology in a
      comprehensive manner. Experimental and clinical studies suggest that 3DE is
      likely to play a valuable role in the evaluation of various cardiac and flow
      disorders and in planning interventions and surgery. In addition, 3DE has been
      applied to derive quantitative measurements of volume, mass and dimensions of the
      left and right ventricles and also other cardiac lesions, such as atrial and
      ventricular septal defects. Every aspect of 3DE is in continuous evolution.
      Faster and more highly automated image processing could make the technique more
      easily applicable in the clinical scenario.

PMID- 11291285
TI  - Fibromatoses of multicentric origin: a case report.
AB  - We experienced a very rare case with fibromatoses of multicentric origin. One of
      the 2 intraabdominal fibromatoses showed a extremely rapid growing and another
      fibromatosis arising from the abdominal wall showed an invasive behavior. All
      lesions were diagnosed and resected simultaneously. This patient has been
      followed for 2 years postoperatively and no recurrent lesion has been detected so
      far.

PMID- 11291286
TI  - Long-term results of facial nerve function after acoustic neuroma surgery-
      clinical benefit of intraoperative facial nerve monitoring.
AB  - The goals in acoustic neuroma surgery should be the total removal of tumor and
      preservation of facial nerve function. The aim of this study is to establish the
      benefit of intraoperative monitoring for the total removal of tumor and the long
      term result of facial nerve function after surgery. Thirty-two patients, who were
      operated on between 1985 and 1995, were divided into two groups: an unmonitored
      (n = 14) and a monitored (n = 18) group. Postoperative facial nerve function was
      followed by a modified House-Brackmann grading (H&B) immediately (initial), and
      at 1 week, 1 month, 6 months and 1 year (final) after surgery. A final H&B grade
      of I/II was taken as the preservation of facial nerve function. Facial nerves
      were preserved anatomically in all cases. A total tumor removal was accomplished
      in 21% of unmonitored group and in 72% of monitored group patients. Final H&B
      (I/II) was achieved in 36% of unmonitored group and in 83% of monitored group
      patients. All 9 patients with initial H&B (I/II) had final H&B (I/II). None of 5
      patients with initial H&B (V/VI) had final H&B (I/II). However, 3 patients showed
      late-recovery of facial weakness at 6 months after surgery. Eighteen patients
      with initial H&B (III/IV) had various degrees of final facial weakness. Among
      them, 12 patients showed early-recovery at 1 month after surgery. In conclusion,
      facial nerve monitoring during acoustic neuroma surgery is useful to improve the
      rates of total removal of tumor and functional preservation of facial nerve. We
      can expect final degrees of facial weakness by initial degrees in conjunction
      with sequential changes in postoperative facial weakness.

PMID- 11291287
TI  - Quality of social network for pregnant women in Japan with focus on parity and
      family structure.
AB  - The purpose of this study was to identify 1) the quality of human network of a
      pregnant woman, and 2) characteristics of a high-risk pregnant woman for
      motherhood due to the shortage of social support. We reviewed social network
      system using a questionnaire: size; nature of relationship with a pregnant woman;
      duration of relationship with her; frequency of contact with her; and distance
      from her residence. We also categorized the subjects according to two typical
      conditions: parity (primigravida or multigravida) and family structure (nuclear
      or extended). The author interviewed 125 subjects in their final trimester,
      living in Narashino City near Tokyo to answer the questionnaires. 117 pregnant
      women agreed and participated in the study. It was found that our subjects had
      the social network consisted of the mean size of 9.0 supportive members (SD =
      1.9), which was similar to that (8.5) reported in the USA by Cronenwett. Our
      subject perceived her husband and mother most important as supportive members. 10
      to 20% of our subjects perceived husbands' mothers, brothers, and even their
      friends as non-supportive members. Roughly 40 to 60% of our subjects did not list
      husbands' fathers, brothers and fathers as network members. We found that
      pregnant women in Japan, especially primigravidas and pregnant women belonging to
      nuclear family, had poor quality of social support network. Pregnant women with
      poor quality of social network were considered as high risk for emotional and
      behavioral problems both to mother and child. Therefore, midwives should be able
      to predict the risk or mental stress in childcare due to shortage of social
      support. This will avoid child abuse through the establishment of necessary human
      network for isolated mothers.

PMID- 11291288
TI  - Establishment of a novel human squamous cell carcinoma cell line from oral
      primary tumor by geneticin treatment.
AB  - A novel cultured cell line NOS-1, derived from a human oral primary squamous cell
      carcinoma (SCC) of the lower gingiva, was established without xenografting the
      tumor into nude mice by means of "Geneticin" treatment, which allowed for
      elimination of contaminated fibroblasts and produced enriched tumor cells at an
      early stage of the culture. NOS-1 cells showed numerous desmosome structures and
      some intermediate filaments. To determine tumorigenicity and to establish an
      orthotopic tissue invasion model for oral carcinoma, the NOS-1 cells were
      injected into the back and the tongue of male athymic nude mice. The back tumors
      showed an expansive growth pattern without significant invasion of surrounding
      tissues, while the tongue-implanted tumors exhibited invasive growth. The
      establishment of a novel oral primary tumor cell line and a new orthotopic tissue
      invasion model is expected to be useful for the study of biological
      characterization and for the identification of the invasive mechanism of human
      oral cancers.

PMID- 11291289
TI  - Antiphospholipid antibodies in children.

PMID- 11291290
TI  - [The effect of prenatal exposure to cadmium on flash visual evoked potentials in
      rat offspring before and after injection of norepinephrine into the lateral brain
      ventricle].
AB  - AIM: It is known that norepinephrine (NE) in low doses increases the amplitude of
      flash visual evoked potential (FVEP). The purpose of this paper was to find out
      if cadmium (Cd) intoxication changes the NE effect on FVEP. MATERIAL AND METHODS:
      18 Wistar albino rats were divided into 3 groups: 6 received 5 ppm, next 6
      received 50 ppm cadmium in drinking water since time of conception and during 21
      days after delivery and 6 as a control group received tap water only. Newborns
      were examined when they were 3 to 6 months old. FVEP were recorded before and
      after injection of 10 microliters saline and then NE into the right lateral brain
      ventricle. Two doses of NE 25 and 50 nmols were used. Amplitudes of the first
      deep negative wave (N1) and the next positive one (P2) were measured from
      isoelectric line to peaks. For statistic analysis the Student t-test was
      performed with statistical significance by p < 0.05. RESULTS: The prolongation of
      N1 and P2 latencies of FVEP was observed in all groups after both doses of NE,
      the differences were statistically significant after doses of 25 nmols NE. The
      amplitude of N1 increased after NE in all groups, in the control one till 205
      225% and 143-151% in Cd groups. The amplitude of P2 in control group was higher
      (109-113%) after NE compared to initial value (100%). Cadmium caused the decrease
      (of 56-90%) after both doses of NE. The differences of amplitudes were
      statistically significant. The prenatal treatment by cadmium caused the lower
      sensitivity of FVEP to NE.

PMID- 11291291
TI  - [Use of AutoTopograf TMS-3 keratoconus screening program for keratoconus
      detection].
AB  - PURPOSE: The purpose of this study was to investigate sensitivity of Klyce-Maeda
      and Smolek-Klyce methods in detection of early or suspect keratoconus by using
      AutoTopographer TMS-3 (Tomey). MATERIAL AND METHODS: At the First Department and
      Clinique of Ophthalmology, Silesian Medical School in Katowice, 175 eyes
      underwent ophthalmological examinations. There were 67 eyes with irregular
      astigmatism, 39 eyes with PRK decentration and 69 eyes with early or suspected
      keratoconus. The procedure was performed with the TMS-3 AutoTopographer (Tomey).
      During the study we investigated index definitions included in Keratoconus
      Screening Program. RESULTS: The examination showed the false positive results: in
      irregular astigmatism (KSI index in 31.3%, KPI index in 10.4%), in PRK
      decentration (KSI and KPS index in 18%). The results of analysis of keratoconus
      detection by Keratoconus Screening Program in early or suspected keratoconus were
      false negative (it means there were no keratoconus symptoms) in KCI index--24.6%,
      in KSI index--11.6% and KPI index--21.7%. CONCLUSION: To sum up, we can say that
      Keratoconus Screening Program is a good program for confirming diagnosis of early
      keratoconus in 80%, but it has to be assisted by a clinical examination.

PMID- 11291292
TI  - [Procedure for keratoconus detection according to the Rabinowitz-Rasheed method-
      personal experience].
AB  - PURPOSE: The purpose of this study was to investigate sensitivity of KISA% index
      to compare with Klyce-Maeda and Smolek-Klyce methods in detection of early or
      suspected keratoconus by using AutoTopographer TMS-3 (Tomey). MATERIAL AND
      METHODS: At the First Department and Clinique of Ophthalmology, Silesian Medical
      School in Katowice, 69 eyes underwent ophthalmological examinations in patients,
      who did not wear contact lenses at least for 6 weeks before examination. The
      procedure was performed with the TMS-3 AutoTopographer (Tomey). During the study
      we investigated index definitions included in Keratoconus Screening Program.
      RESULTS: The examination showed the false negative results in 29% patients with
      early or suspected keratoconus. Using KISA% index we detected false negative
      results in 5.8% patients with early or suspected keratoconus. CONCLUSION: To sum
      up, we can say that the KISA% index is highly sensitive and specific for
      diagnosing keratoconus, more useful than Klyce-Maeda and Smolek-Klyce methods.
      This method can be used by users of all types of videokeratoscopes.

PMID- 11291293
TI  - [Surgical correction of astigmatism after wedge resection keratoplasty].
AB  - PURPOSE: To analyse the results of astigmatism correction after keratoplasty
      using wedge resection technique. MATERIAL AND METHODS: Eleven patients underwent
      a wedge resection for postkeratoplasty astigmatism. The average postoperative
      astigmatism was 13.9 diopters (range 11.0 to 17.0 D). Among the patients there
      were 5 women and 6 men, aged 25 to 70 years. All of the grafts were in static
      phase, after suture removal. The indications for keratoplasty were: keratoconus-
      8, pseudophakic and aphakic corneal edema--3. The follow-up period after wedge
      resection was 6 to 24 months. The astigmatism was evaluated by videokeratometer
      (ORC Masterviue Ultra). RESULTS: Postoperatively, the average astigmatism was
      7.25 D by 6 months, 8.1 D by 12 months, 8.45 D by 24 months. The visual acuity
      corrected with spectacles was 0.2 to 1.0. 8 patients (72.7%) gained better visual
      acuity. Complications included: 1) growing vessels through the wound, 2) delay of
      epithelization. CONCLUSION: Wedge resection is an effective technique for
      managing postkeratoplasty high astigmatism.

PMID- 11291294
TI  - [Transpupillary thermotherapy combined with 106Ru as a method of managing
      choroidal melanoma].
AB  - BACKGROUND: A study was carried out to evaluate the effectiveness of
      transpupillary thermotherapy (TTT) with diode laser applied as adjuvant treatment
      to 106Ru brachytherapy in choroidal melanoma. These two methods coined as
      "sandwich therapy" are complementary and allow to decrease the dose of radiation.
      MATERIAL AND METHODS: Between November 1996 and December 1997, 45 patients with
      choroidal melanoma were treated simultaneously with 106Ru and TTT. There were 18
      males and 27 females, aged 20 to 78 (mean 57). There were 7 tumors with height of
      5 mm or less, 28 ranging 5.43-8.63 mm and 10 with height 9 mm or more. The
      anterior tumor margin was located in the equator area or posterior to it in 71.1%
      of cases. The laser treatment was delivered using spots 2-3 mm in size, at a mean
      power 600 mW, for about 1 minute. The mean radiation dose was 60 Gy to the tumor
      apex. The follow-up ranged from 12 to 24 months. RESULTS: Reduction in tumor
      height by at least 30% was exhibited in 35 (77.8%) tumors, in one evaluated as
      positive result it was 27%. There was no improvement after treatment in 4 cases,
      2 eyes were enucleated. A significant relationship was found between tumor
      thickness and the result of treatment. CONCLUSION: Our preliminary observations
      suggest that TTT combined 106Ru brachytherapy is an effective method of
      treatment. A longer follow-up is needed to assess final local results and the
      impact of treatment on survival.

PMID- 11291295
TI  - [Immunologic disturbances in patients with idiopathic posterior uveitis].
AB  - PURPOSE: This study aimed to evaluate the immune system function in patients with
      idiopathic posterior uveitis. MATERIAL AND METHODS: 50 patients--29 women (58%)
      and 21 men (42%)--were examined. Intraocular inflammation intensity was scored on
      standard uveitis grading system prepared by BenEzra et al. In all cases selected
      parameters of serum immune system activity--immunoglobulins IgA, IgG, IgM, IgE,
      complement proteins C3c and C4, circulating immune complexes (CIC) and
      autoantibodies: ANA, ANCA, ACA were detected. All immune system parameters were
      assessed in active stage of the disease and then 1, 3, 6, 12 months after the
      beginning of immunosuppressive therapy. RESULTS: Among 50 patients immunological
      abnormalities were found in 38 cases (76%). Changes in serum immunoglobulin
      concentrations were present in 28 patients and the most common pathology was the
      deficiency of serum IgG in 11 subjects. In 34 cases abnormalities of the
      complement system were present. In 43 subjects serum CIC were detected. ANA in
      indirect immunofluorescence test were found in 9 patients. Neither ANCA nor ACA
      were present in serum of this group of patients. CONCLUSIONS: Non specific
      abnormalities of immune system parameters found in serum of 38 patients with
      idiopathic posterior uveitis can indicate their role in pathogenesis of this
      disease. The deficiency of IgG can be related to CIC formation in this group of
      patients. Probably circulating immune complexes (CIC) are involved in the
      pathogenesis of endogenous posterior uveitis and they can act as an aggressor or
      protector against the retinal autoimmune mechanisms.

PMID- 11291296
TI  - [Interdependency between titers of aniretinal antibodies and selected immune
      system parameters in serum of patients with endogenous posterior uveitis].
AB  - PURPOSE: To evaluate serum antiretinal antibodies and selected immune system
      activity parameters in patients with endogenous posterior uveitis. MATERIAL AND
      METHODS: 50 patients--29 women (58%) and 21 men (42%)--aged 15-70 with idiopathic
      posterior uveitis were examined. Intraocular inflammation intensity was scored on
      standard uveitis grading system prepared by BenEzra et al. In all cases selected
      parameters of serum immune system activity--immunoglobulins: IgA, IgG, IgM, IgE,
      complement proteins: C3c, C4, circulating immune complexes (CIC) and
      autoantibodies: ANA, ANCA, ACA, were detected. The serum levels of ARA were
      determined by indirect immunofluorescence test on normal monkey retina as a
      substrate and FITC-labelled anti-human IgA, IgG, IgM serum (Euroimmun, Germany).
      All immune system parameters were assessed in active stage of the disease and 1,
      3, 6, 12 months after the beginning of immunosuppressive therapy. RESULTS: In 38
      patients (76%) non specific abnormalities of serum immune system activity
      parameters were found. During the follow-up period the changes in serum
      concentrations of immune system parameters were not statistically significant.
      Before treatment ARA were present in serum of 40 patients (80%). The distinct
      decreasing of serum ARA levels was present during the whole time of observation.
      The statistical analysis did not show any correlation between the serum
      concentration of selected immune system parameters and ARA. However, the presence
      of two various tendencies between ARA and CIC serum levels co-fluctuations were
      observed. In subjects with absence or low CIC serum concentrations, high serum
      ARA levels were found and the uveitis was severe. In cases with high CIC serum
      concentrations, low ARA levels were present and the disease course was mild.
      CONCLUSION: The interdependency between CIC and ARA has probably an essential
      role in the pathogenesis of idiopathic posterior uveitis.

PMID- 11291297
TI  - [The seasonal course of recurrent uveitis in children and youth].
AB  - PURPOSE: To analyse the etiology, localisation of inflammation, frequency of
      recurrences and the visual function in the course of uveitis in children.
      MATERIAL AND METHODS: Sixteen children aged 4-18 years with uveitis were analysed
      for 2 to 15 years (mean 6.3 years) from the occurrence of the first symptoms. The
      ophthalmological examination, laboratory investigations, pediatric, stomatology
      and laryngology consultations were performed in all children. The medical topical
      and general treatment in all patients was applied. RESULTS: The certain
      etiological factors were found in 9 patients, the probable ones in 2 children and
      in 5 cases the cause of the illness was not established. Clinical inflammation
      was located in different parts of uvea, in 10 children it appeared in one eye and
      in 6 children in both. The course of illness showed a recurrent character (from 1
      to 8 recurrences) in most children. We have established three seasonal
      occurrences of the disease, mainly in spring and autumn, less at the beginning of
      summer. After treatment the visual acuity improved in 17 eyes (77.3%), in 3 eyes
      (13.6%) it did not change and in 2 eyes (9.1%) got worse. CONCLUSIONS: The
      chronic, recurrent uveitis in children has a seasonal character (three times a
      year). The rheumatic disease is the main cause of multiple recurrences of uveitis
      in children. The early diagnosis of illness and careful medical supervision until
      the children are 16-18 years old may improve the final results of treatment.

PMID- 11291299
TI  - [Tuberous sclerosis--case report].
AB  - A case of 37-year-old man with tuberous sclerosis is presented. Classic triad
      (Vogt) which consists of mental handicap, epilepsy and adenoma sebaceum around a
      nose and cheeks was observed. Ophthalmoscopy showed bilateral retinal
      astrocytomas with mulberrylike appearance. During 6 years follow-up small
      progression of ocular changes (findings) was noticed. CT and NMR of the head,
      ultrasound of the eye fluorescein and ICG angiography are presented.

PMID- 11291298
TI  - [Thrombin-antithrombin III complexes in plasma and subretinal fluid in patients
      with perforated retinal detachment].
AB  - PURPOSE: To study the thrombin generation in plasma and subretinal fluid (SRF) by
      evaluation of thrombin-antithrombin III complexes (TAT) and antithrombin III (AT
      III) activity in patients with rhegmatogenous retinal detachment. MATERIAL AND
      METHODS: Prospective study of 54 patients subjected to retinal detachment
      surgery. Patients with vein or arterial disease and with other factors which
      could change evaluated parameters were excluded. Subretinal fluid samples were
      obtained at the time of routine drainage during retinal detachment surgery.
      Venous blood samples were taken from the cubital vein to natrium citrate solution
      (9:1) immediately after induction of anaesthesia but before surgery. TAT
      concentration in citrate plasma and in SRF was assessed in 22 patients aged from
      15 to 78 years (mean: 49.5 years). AT III activity in blood plasma and SRF was
      measured in 32 patients aged from 20 to 77 years (mean: 53.8). The correlations
      between the TAT concentration in SRF were evaluated as well as AT III activity in
      SRF, and age, sex of patients, the duration and extent of retinal detachment,
      number of retinal tears and the cryopexy application. RESULTS: The median value
      of TAT concentration in citrate plasma was 9.08 micrograms/l (interquartile
      range: 59.3 micrograms/l). In 20 cases out of 22 eyes studied TAT levels were
      higher than 60 micrograms/l. The mean level of AT III activity in blood plasma
      was 105% (SD: 24.0%). The median level of AT III activity in 32 samples of SRF
      was 16.5% (interquartile range: 14.5%). The levels of AT III in SRF were
      significantly lower than AT III values in blood plasma (p < 0.001). We found no
      correlation between the levels of AT III activity in plasma and AT III activity
      in SRF nor between TAT concentration, AT III activity in SRF and sex, age of
      patients, the degree of myopia, the duration and extent of retinal detachment,
      nor retinal degenerative changes and cryopexy application. CONCLUSION: Our study
      revealed high TAT concentration and AT III activity and in all studied samples of
      SRF disclosing the signs of thrombin generation in SRF.

PMID- 11291300
TI  - [Arteriovenous communication of the retina--case report].
AB  - In this paper I have described a rare case of typical arteriovenous communication
      of the retina (ACVR), also called racemose haemangioma, but with some atypical
      traits. A case of a young white 22-year-old woman is presented. AVCR was
      recognised in her left eye, II stage according to Archer's classification,
      therefore neither intracranial haemangioma nor vascular decompensation of retina
      was observed. In the standard ophthalmic examination, including automated
      perymetry and fluorescein angiography, the following phenomena were not seen yet
      or they were rarely described: pigmented muffs on some changed vessels, mainly
      nasal location of AVCR, parallel AVCR existed between both great and precapillar
      vessels and macular changes: yellowish ring surrounded the central fovea. Visual
      acuity of the affected eye was 1.0 and the patient did not complain about it.

PMID- 11291301
TI  - [Management of selected complications of trabeculectomy].
AB  - Current opinions concerning the value of trabeculectomy performed in adults and
      children are presented and compared with author's own experiences. The
      probability of intra- and postoperative complications especially hypotonia and
      malignant glaucoma, are discussed.

PMID- 11291302
TI  - [Current methods of imaging morphologic changes of the optic nerve head during
      the course of glaucoma].
AB  - The present review describes currently available methods of imaging morphologic
      changes of the optic nerve head in glaucoma and discuss their possibilities and
      potential limitations in diagnosing and monitoring patients with glaucomatous
      neuropathy.

PMID- 11291303
TI  - [Epidemiology of myopia].
AB  - The present state of knowledge on the epidemiology of myopia is discussed. The
      history of myopia investigations is described. The prevalence of myopia in
      different ages, races and populations is presented. The factors influencing
      myopia occurrence are characterized. Special attention is focused on the results
      of studies indicating environmental and genetic reasons of myopia. Most recent
      investigations concerning the influence of light on myopia occurrence as well as
      concerning a genetic locus for high myopia are described.

PMID- 11291304
TI  - [Purtscher's retinopathy--anatomic and pathogenic determinants in the evolution
      of the disease].
AB  - The paper presents the cases of bilateral acute ischaemia in the central and
      peripapillary retina during acute pancreatitis. The authors discuss the typical
      clinical picture, natural history of the disease and possible pathogenical
      mechanisms of the embolisation of terminal retinal arterioles.

PMID- 11291305
TI  - A modelling study of feedforward activation in human erythrocyte glycolysis.
AB  - Though feedforward activation (FA) is a little known principle of control in
      metabolic networks, there is one well-known example; namely, the activation of
      pyruvate kinase (PK) by fructose-1,6-biphosphate (FBP) in glycolysis. The effects
      of this activation on the enzyme's kinetics are well characterised, but its
      possible role in glycolytic control has not been determined, and, experimentally,
      there is as yet no direct way of modifying the enzyme to remove just the FBP
      activation without affecting other aspects of the enzyme's kinetics. Given this
      limitation, we used a detailed numerical simulation of human erythrocyte
      glycolysis to simulate the effects of selective removal of the activation of PK
      by FBP on steady-state metabolite concentrations and on the dynamic response of
      glycolytic flux to a sudden increase of the cell's demand for ATP. Our modelling
      results predict that in the absence of FA steady-state levels of metabolites
      within the activation loop, i.e. from FBP to phosphoenolpyruvate, would be four-
      to thirteen-fold higher than normal, whereas levels of ATP and metabolites
      outside the loop, i.e. glucose-6-phosphate, fructose-6-phosphate and pyruvate,
      would be lower than normal. Existing clinical evidence in a patient with
      haemolytic anaemia, correlated with a lack of activation of PK by FBP (Paglia
      D.E., Valentine W.N., Holbrook C.T., Brockway R., Blood (1983) 62 972-979), is
      consistent with this prediction. In response to changing demand for ATP, the
      model predicts that the corresponding change of glycolytic flux would entail
      changes of metabolite concentrations in the absence of FA, but that in its
      presence the levels of metabolites within the activation loop remain essentially
      unperturbed. Thus, our results suggest that by stabilising metabolite pools in
      the face of variable glycolytic flux, FA may serve to avoid perturbations of the
      oxygen affinity of haemoglobin (sensitive to the levels of 2,3-phosphoglycerate)
      and of cell osmolality that would otherwise occur during variations in the cell's
      demand for ATP. In addition, by significantly raising the steady-state setpoint
      of intermediate metabolite pools, the productivity index (ratio of glycolytic
      flux to total metabolites in the pathway) of glycolysis would fall almost four
      fold in the absence of forward activation.

PMID- 11291306
TI  - Composition strand asymmetries in prokaryotic genomes: mutational bias and biased
      gene orientation.
AB  - Most prokaryotic genomes display strand compositional asymmetries, but the
      reasons for these biases remain unclear. When the distribution of gene
      orientation is biased, as it often is, this may induce a bias in composition, as
      codon frequencies are not identical. We show here that this effect can be
      estimated and removed, and that the residual base skews are the highest at third
      base codon positions and lower at first and second positions. This strongly
      suggests that compositional asymmetries result from 1) a replication-related
      mutational bias that is filtered through selective pressure and/or from 2) an
      uneven distribution of gene orientation. In most cases, the mutational bias
      alters the codon usage and amino acid frequencies of the leading and the lagging
      strand. However, these features are not ubiquitous amongst prokaryotes, and the
      biological reasons for them remain to be found.

PMID- 11291307
TI  - From gene to protein in higher plant mitochondria.
AB  - Higher plant mitochondria contain a genetic system with a genome, transcription
      and translation processes, which have to be logistically integrated with the two
      other genomes in the nucleus and the plastid. In plant mitochondria, after
      transcripts have been synthesised, at least in some cases by a phage-type RNA
      polymerase, they have to go through a complex processing apparatus, which depends
      on protein factors imported from the cytosol. Processing involves cis- and trans
      splicing, internal RNA editing and maturation at the transcript termini, these
      steps often occurring in parallel. Transcript life is terminated by RNA
      degradation mechanisms, one of which involves polyadenylation. RNA metabolism
      seems to be a key element of the regulation of gene expression in higher plant
      mitochondria.

PMID- 11291308
TI  - Non-independence of individuals in a population of Drosophila melanogaster:
      effects on spatial distribution and dispersal.
AB  - We used a simple quadrat analysis to globally categorise the spatial distribution
      of Drosophila melanogaster individuals. Individuals were spatially aggregated and
      this was not only due to sexual attraction. This aggregation seemed to be
      maintained during dispersal, hence explaining the great variability of this
      behaviour observed in our work and by other authors. Thus, individuals are
      expected to arrive as small groups into a new patch. This may induce costs
      through competition and benefits by ensuring the presence of reproductive mates
      and/or if there is a phenomenon of local resource enhancement by the presence of
      conspecifics, hence influencing the evolution of dispersal.

PMID- 11291309
TI  - Overexpression of SR-BI in hamsters treated with a novel ACAT inhibitor (F12511).
AB  - The effect of a novel acyl-coenzyme A: cholesterol acyltransferase (ACAT)
      inhibitor on cholesterol metabolism was studied in hamsters. Oral administration
      of F12511 (10 mg/kg/d) for 4 weeks produced a decrease in dietary cholesterol
      absorption (-18%) and in the liver concentration of esterified cholesterol (
      75%), as compared with control values in untreated hamsters. While the hepatic
      expression of LDLr was unchanged by the treatment, that of SR-BI was increased
      (+142%), which suggests that the hepatic expression of SR-BI could be upregulated
      by a depletion of the cholesterol stores, due to ACAT inhibition. This SR-BI
      overexpression, however, did not induce a fall in plasma HDL-cholesterol
      concentration, in contrast with previous reports in transgenic mice
      overexpressing SR-BI at a higher extent.

PMID- 11291310
TI  - First determination of arthropod assemblages associated with Erica arborea L. and
      Erica scoparia L.
AB  - This study gathers the first data concerning the arthropod assemblages associated
      with Erica arborea L. and E. scoparia L. It demonstrates that it is necessary to
      sample at least ten Erica scoparia L. to give a representative image of its
      arthropod assemblage. This study reveals that neither plant size nor architecture
      nor floristic environment can explain the different patterns of colonisation of
      both species of Erica by the arthropod assemblages. If our attention is focused
      on the three main species collected on both species of Erica, it appears that the
      nearly exclusive presence of Sitona lineatus L. on E. arborea L. might be
      correlated with highly different concentrations in tannins between the two
      species of Erica. In contrast, the different patterns of colonisation and the
      number of individuals of Colaspidea oblonga Blanchard collected on both species
      of Erica might be linked to the life-history of this Chrysomelideae. Finally, the
      presence of Psallus crotchi Scott to the same extent on both Erica species can be
      connected to the destruction of its natural host-plant and to the similar
      concentrations of nitrogen, a limiting factor for sap-sucker's colonisation, in
      both Erica species.

PMID- 11291311
TI  - Dioecy in Fitzroya cupressoides (Molina) I.M. Johnst. and Pilgerodendron uviferum
      (D. Don.) Florin (Cupressaceae).
AB  - The aim of this study was to determine the dioecious or monoecious condition of
      Fitzroya cupressoides and Pilgerodendron uviferum. The study area lies west of
      the Nahuel Huapi National Park in northern Patagonia (Argentina), where these
      species form mixed stands. One hundred individuals of each species were studied
      over three successive years. The nature and position in the crown of their
      reproductive organs were recorded. Results showed that both species are
      dioecious. This feature has been confirmed on trees of these species growing in
      other sites within their natural distribution area in Argentina and Chile.

PMID- 11291312
TI  - COOH-terminal truncated human cardiac MyBP-C alters myosin filament organization.
AB  - Myosin-binding protein C (MyBP-C) is thought to play structural and/or regulatory
      role in striated muscles. The cardiac isoform of MyBP-C is one of the disease
      genes associated with familial hypertrophic cardiomyopathy and most of the
      mutations produce COOH truncated proteins. In order to determine the consequences
      of these mutations on myosin filament organization, we have characterized the
      effect of a 52-kDa NH2-terminal peptide of human cardiac MyBP-C on the alpha
      myosin heavy chain (alpha-MyHC) filament organization. This peptide lacks the
      COOH-terminal MyHC-binding site and retains the two MyHC-binding domains located
      in the N-terminal part of MyBP-C. For this characterization, cDNA constructs (rat
      alpha-MyHC, full-length and truncated human cardiac MyBP-C) were transiently
      expressed singly or in pairwise combination in COS cells. In conformity with
      previous works performed on the skeletal isoform of MyBP-C, we observed that full
      length cardiac MyBP-C organizes the MyHC into dense structures of uniform width.
      While the truncated protein is stable and can interact with MyHC in COS cells, it
      does not result in the same organization of sarcomeric MyHC that is seen with the
      full-length MyBP-C. These results suggest that the presence of truncated cardiac
      MyBP-C could, at least partly, disorganize the sarcomeric structure in patients
      with familial hypertrophic cardiomyopathy.

PMID- 11291313
TI  - [Prospective research on the duality between morphological traits and plant
      competitive capacity: the case of weed species and wheat].
AB  - Competitive abilities of plants were interpreted by measuring their morphological
      traits in interspecific competitive cultivation conditions. Measurements were
      realised by a comparative approach with interspecific cultivation of fourteen
      arable weeds growing with a domestic species cultivated at a large scale: the
      winter wheat (Triticum aestivum var Darius). Results show that arable weeds
      characterised by an important biomass and allocation of biomass to the stems are
      responsible for a decrease in wheat biomass, and for the ear, a decrease in
      height, biomass and number of seeds. These results are discussed in view of
      predicting competitive abilities of arable weeds with a simple method and for the
      conservation of arable weeds since some of them are among the most threatened
      species of the European flora.

PMID- 11291314
TI  - [The establishment of Holocene vegetation belts: quite near to a complete model
      of a solid mass].
AB  - Pollen and macro-remains were analysed in a sixth site (La Gouille 1,800 m) of
      the Chaine des Hurtieres (northern French Alps). Nine A.M.S. dates support the
      chronology. Thus, the establishment of the vegetation belt of a massif can be
      modelled in the northern French Alps. Betula invaded sub-Alpine grasslands as
      early as 10,000 14C BP. Around 9,600 14C BP shrublands with Corylus, Alnus and
      Sorbus were established before the spread of Abies at the site approximately
      8,200 14C BP. A decrease in Abies prior to 8,100 14C BP occurred during the
      Venediger climatic oscillation. At around 2,940 14C BP, a strong regression of
      Abies due to human action is noted with the expansion of Alnus viridis. Recently,
      a second Abies retraction led to the present sparce P. cembra and Alnus viridis
      vegetation cover.

PMID- 11291315
TI  - [Variability of muscular and articular forces of the thumb. Comparison of three
      results during lateral grip].
AB  - The aim of this paper is to describe three different laboratory studies of
      muscular and articular forces in the thumb and to compare and discuss their
      results in term of constraints (forces and moments) at the carpometacarpal joint
      during key pinch. Imaging techniques such as biplanar roentgenograms or computer
      tomography imaging were used on cadaver hands and magnetic resonance imaging on
      living hands in order to determine bone dimensions, muscle and tendon forces,
      directions, and centres of rotation. Mechanical models of free bodies with three
      to five links were created. Problems of balancing of static forces were solved
      using different methods (electromyography, systematic combination of muscular
      forces or optimization method). The results in terms of muscular forces or
      constraints at the carpometacarpal joint showed a strong variability (one to
      three depending on method and hypothesis). However the three studies all showed
      subluxation of the carpometacarpal joint balanced by joint constraints. Finally,
      it was demonstrated using magnetic resonance imaging, that results were strongly
      influenced by the exact point of application of the forces.

PMID- 11291316
TI  - [In vivo cinematic study of the trapezometacarpal joint].
AB  - The aim of this study was to assess the trapeziometacarpal joint kinematics from
      in vivo measurements, both quantifying the ranges of motion and suggesting a
      suitable joint model. A motion analysis system has been used to collect the
      spatial trajectories of markers, glued respectively on the thumb and on the
      hand's palm. A rigorous protocol was set up to make sure of the trapezoid bone's
      fixity relatively to the hand, and then to be able to characterize the movement
      of the first metacarpus with respect to the trapezium. The ranges of motion have
      been measured on two distinct movements: circumduction and flexion-extension, and
      different types of joints: healthy, pathological and prosthetic. The joint axes
      of rotation (for flexion-extension and ante-retroposition movements) have been
      determined on healthy subjects. The computation of rotation amplitudes and
      positions of joint axes was based upon the finite helical axis concept, which
      degenerates into finite rotation axis when translations can be neglected. Both
      the measurement protocol and the calculation method have been validated by
      comparing the computed joint center with that measured on a radiography, in the
      case of a spherical prosthesis. The ranges of motion obtained on the healthy
      subject series were consistent with values published by other authors.
      Comparisons have been realized between these reference joints and different
      cases: arthrodesis, arthrosis and prosthesis. The determination of rotation axes
      of a normal joint has lead to a generalized cardan joint, i.e. two non
      perpendicular converging rotation axes.

PMID- 11291317
TI  - [Importance of the posteromedial trapezometacarpal ligamentous complex].
AB  - Pronation and supination of the human thumb has both a practical and a symbolic
      importance. In supination the thumb caresses but in pronation it grasps. The
      articular surfaces of the trapezium and first metacarpal are not congruent enough
      in themselves to assure pronation and supination, but their reciprocal saddle
      shape causes them to have two distinct orthogonal "fundamental" axes of rotation,
      and hence two "privileged" planes of rotation. The one corresponds to the
      movements of the lateral pinch grip and the other to opposition and counter
      opposition of the thumb. The important ligaments are situated on both sides of
      the trapeziometacarpal joint. The posteromedial ligamentous complex is composed
      of the posterior oblique ligament, the anterior oblique ligament, the
      intermetacarpal ligament, and a fourth or more anteromedial ligament which we
      have called the retinaculometacarpal ligament by reason of its proximal
      insertion. It plays an essential role in suspending and anchoring the base of the
      first metacarpal. By its action it induces two types of motion: 1) a discrete
      translation of the metacarpal along the articular concavity of the trapezium in
      lateral pinch grip; 2) a more important motion characterised by a prosupination
      of 90 degrees during its rotation in the plane of opposition. The anterolateral
      ligament's action is restricted to strengthening the action of the posteromedial
      ligaments in the extreme positions of closing of lateral pinch and thumb
      opposition. In cases of trapeziometacarpal subluxation it prevents a complete
      dislocation. These various observations have significant clinical and therapeutic
      implications.

PMID- 11291318
TI  - [Total trapezometacarpal prostheses: concepts and classification study].
AB  - This paper is an attempt to classify the different types of trapezio-metacarpal
      total prostheses according to their bio-mechanical principle and to compare the
      bio-mechanics of these prostheses to that of the normal trapeziometacarpal joint.
      The trapeziometacarpal joint has two approximate centres of rotation (one in the
      proximal metacarpal, one in the trapezium), two degrees of freedom and two arc of
      mobility about 70 degrees. The mechanical model of the trapeziometacarpal joint
      is a universal-joint called "cardan" with three constraint forces (one axial
      compression force, and two shear forces, radial and posterior) and one constraint
      moment around the longitudinal axis. The trapeziometacarpal prostheses may be
      classified in two main categories: the most frequently used are the "ball and
      socket" prostheses. Several prostheses, including the surface replacement
      prostheses have the mechanical characteristics of an universal joint (cardan).
      Ball and socket prostheses have one centre of rotation, 3 degrees of freedom,
      three constraint forces in three directions and no constraint moment when
      "cardan" or surface prostheses have two centres of rotation and 2 degrees of
      freedom; three constraint forces and one constraint moment. Trapeziometacarpal
      prostheses may also be classified according to their arc of mobility, or
      according to their mode of primary fixation (cemented, non-cemented), "press
      fit", expansion and to their secondary fixation (hydroxyapatite).

PMID- 11291319
TI  - [Definition and classification of basal joint osteoarthritis. A critical analysis
      and proposals. Treatment options].
AB  - Several definitions and classifications of basal joint osteoarthritis exist. Each
      of them can be criticized. The authors propose to define basal thumb
      osteoarthritis as osteoarthritis of the trapezometacarpal joint associated or not
      with lesions of scapho-trapezio-trapezoid and/or metacarpophalangeal joints. The
      proposed classification is derived from the Eaton-Littler classification. Stage O
      is identical to stage I of the Eaton-Littler classification: trapeziometacarpal
      instability without cartilage lesions. Stage I is osteoarthritis of the
      trapeziometacarpal joint only, without metacarpophalangeal deformity. Stage II is
      trapeziometacarpal osteoarthrites combined with reductible hyperextension
      deformity of the metacarpophalangeal joint. Stage III is trapeziometacarpal
      osteoarthrites combined with irreductible metacarpophalangeal deformity. Stage IV
      is identical to stage IV of the Eaton-Littler classification: combined
      trapeziometacarpal and scapho-trapezio-trapezoid osteoarthritis. The advantage of
      the proposed classification is that basal joint osteoarthritis is not only
      defined as real or potential (stage O) osteoarthritis of the trapeziometacarpal
      joint, but also includes precise evaluation of two other joints at the base of
      the thumb. This classification can be a guide for treatment options.

PMID- 11291320
TI  - [Comparison of primary trapezometacarpal cup fixation using mechanical tests].
AB  - INTRODUCTION: In order to optimise the primary fixation of the cup of the Arpe
      (Biomet Merck) trapeziometacarpal prosthesis, several geometries have been
      studied. The mechanical strengths of the primary fixations ensured by cup "with
      slots", "bladed" and "with crown", have been assessed and compared to the one
      obtained for the primary anchorage of the Arpe cup. METHOD: For each cup, the
      strength of the primary fixation has been assessed in torsion (torque along the
      cup axis) and bending (torque perpendicular to the cup axis). Tests have been
      performed on prototype cups set up in a vertebral body of lamb cancellous bone.
      Torque recording allowed the assessment of the maximum strength for each cup
      type. RESULTS: Arpe and cup "with slots" showed an effective bending strength,
      respectively due to the three anchorage picks and to the equatorial over
      thickness. However, the cup "with crown" demonstrated a better bending strength
      with a mean torque of pulling out Cbending = 0.89 Nm. In torsion, the three
      anchorage picks of the Arpe cup did not allow a solid anchorage. For such a
      loading, the cup "with crown" also showed the best torsion strength with a mean
      unsealing torque Ctorsion = 0.83 Nm. DISCUSSION: The equatorial over-thickness
      seems to give good bending and torsion strengths to the "bladed" and "with crown"
      cups, with a press-fit effect. Replacing the fixation points of the Arpe cup by a
      crown also allowed the improvement of its torsion strength.

PMID- 11291321
TI  - [Longevity factors in total trapezometacarpal prostheses].
AB  - We report the long term outcome of the trapeziometacarpal prosthesis in a
      personal series of 13 cases with a follow-up ranging from 12 to 17 years. This
      ball and socket prosthesis with a metal on polyethylene pairing is cemented.
      Several modifications were performed along the years: such as increased range of
      motion, better fit between the metacarpal medullary canal and the proximal part
      of the stem and addition of a versatile, intermediate component in order to re
      establish length of the first ray. The status of the metacarpo-phalangeal joint
      is critical. Natural hyperextension of this joint has been seen in about two
      third of th normal individuals. If the metacarpal component become loose, the
      thumb column become shorter and hyperextension of the metacarpophalangeal joint
      is followed by an adduction contracture of the metacarpal which produces a shear
      force component on the cup and finally the loosening of the cup (sequential
      loosening). Keeping or re-establishing the length of the first ray is the major
      principle in the trapeziometacarpal prosthesis. On the other hand,
      metacarpophalangeal arthrodesis is a contraindication for a trapeziometacarpal
      prosthesis. Trapeziometacarpal prosthesis should only be used as a last resort
      when there is severe pain. If the dominant hand is involved, intensive use is a
      contraindication. The trapezium must be large enough to accommodate the cup. The
      author recommends a posterior approach which preserve the anterior ligaments and
      allows a proper bone resection and a good positioning of the cup.

PMID- 11291322
TI  - [Problems with the metacarpophalangeal joint in the surgical treatment of
      osteoarthritis by inserting an ARPE type joint prosthesis].
AB  - Progressive ankylosis of the trapeziometacarpal joint in flexion-adduction with
      closure of the first web in advanced trapeziometacarpal osteoarthritis gradually
      leads to compensatory dislocation of the metacarpophalangeal joint with
      hyperextension in the sagittal plane and abduction in the frontal plane. This
      deformity of the MP joint, initially reducible, but subsequently irreducible,
      results in the classical 'Z' deformity of the thumb in the sagittal plane. A less
      well known 'Z' deformity can also occur in the frontal plane due to distension of
      the medial collateral ligament. Surgical treatment of trapeziometacarpal
      osteoarthritis by arthroplasty must correct this secondary deformity of the MP
      joint to obtain an optimal result. The classical sagittal 'Z' deformity of the
      thumb can be easily corrected while this deformity is still reductible by
      releasing the fist metacarpal by tightening the abductor pollicis longus. When it
      is irreducible, this deformity can only be treated by MP arthrodesis, which
      contraindicates insertion of the ARPE trapeziometacarpal implant. Correction of
      the frontal 'Z' deformity of the thumb requires repair of the medial collateral
      ligament of the MP joint by ligamentorraphy (retightening) or ligamentoplasty.

PMID- 11291323
TI  - [Trapezometacarpal ligamentoplasty: personal technique].
AB  - We describe a new procedure of trapeziometacarpal ligamentoplasty. This
      ligamentoplasty is both passive and active. The operation is performed in three
      stages: (1) Transfert of part of the abductor pollicis longus in a posterior and
      distal direction; (2) Transfert of the radial part of the extensor carpi radialis
      longus into the proximal first metacarpal; (3) Forming a loop around the flexor
      carpi radialis tendon with a distally inserted slip of abductor pollicis longus.

PMID- 11291324
TI  - [The Roseland prosthesis in the treatment of osteoarthritis. A five years
      experience with the same surgeon].
AB  - INTRODUCTION: The results of the Roseland trapeziometacarpal prosthesis in the
      treatment of the TMP arthritis has been reviewed and the trapezial component
      fixation discussed. METHOD: The material has been collected between November 1995
      and January 2000. The immobilisation lasted 15 days if the prosthesis was
      cemented and one month if not. The following criteria were studied: pain,
      opposition, first and the second metacarpal angle, patient satisfaction, X-rays
      data, surgeon opinion on the components position, complication and re-operation.
      RESULTS: The series is made of 45 cases (43 patients), eight males and 37
      females. The average age was 59.7 years, with an average pre-operative duration
      of 3.5 years. X-rays data shows 43% with Dell II and 33% with Dell III aspect. 19
      prosthesis were cemented, 22 not, 9 cases had a mixed fixation. The average
      follow up is 14 months. There was no or few post-operative pain (74% of cases).
      The opposition has been improved in most of the cases. 78% of the patients were
      satisfied. Post-operative X-rays were correct in 66% for the trapezial component
      and in 86.5% with the metacarpal one. There were 12 complications, with eight
      trapezial component failures. Eight patients were re-operated on. All cases were
      satisfying then. DISCUSSION: If some foreign causes occurred in some
      complication, six failures were due to a technical problem. We must point out the
      frequency of failure with the cemented trapezium. However, the Roseland
      prosthesis is a satisfying arthroplasty but the trapezial component implantation
      must be improved.

PMID- 11291325
TI  - [The Roseland prosthesis].
AB  - Total joint replacement of the trapezio-metacarpal (TMC) joint is one of the
      procedures available for the surgical treatment of degenerative osteoarthritis or
      rheumatoid arthritis of the first carpometacarpal joint. A four French Alpine
      surgeon group, (C. Lebrun, P. Massart, F. Moutet and C. Sartorius) have developed
      a new cementless total TMC joint prosthesis: the Roseland prosthesis. Such a
      device tries to improve the biomechanical conditions of the La Caffiniere's
      implant, which was introduced in 1973. Clinical data of a 24 patients with a 38
      month mean follow-up series are reported.

PMID- 11291326
TI  - [Rubis 2 trapezometacarpal prosthesis: concept, operative technique].
AB  - INTRODUCTION: We have implanted 49 uncemented reversed trapeziometacarpal
      prostheses since 1997. OPERATIVE TECHNIQUE: We used a classical dorsal approach.
      A good preparation of the base of the first metacarpal will give excellent
      exposure of the trapezium, the most important stage of the operation.
      Instrumentation allows easy insertion of the two components and also their
      adjustment. RESULTS: A follow-up of three years is too short and we intend to
      give our full results at five years. At the present time the patients are well
      and seem satisfied. DISCUSSION: The reversed design of this prosthesis is useful
      because it spares the scarce bone stock of the trapezium. The shape of the
      trapezial implant prevents not only its sinkage but also any lateral movement.

PMID- 11291327
TI  - [ARPE prosthesis: preliminary results].
AB  - Preliminary results of 45 trapeziometacarpal "ARPE" prostheses are reported with
      a mean follow-up of 22.4 months. Pain and mobility before and after operation
      were analysed. A special questionnaire was used to assess the result in activity
      of daily living. Pre and postoperative special X rays were also compared. Pain
      decreased in frequency and intensity and mobility improved. 97.1% of the patients
      were satisfied with their prosthesis after the operation. Comparison are pre- and
      postoperatives radiographs showed a tendency for both cup and stem to
      progressively sink into the bone.

PMID- 11291328
TI  - [A minimal trapezometacarpal ligamentoplasty].
AB  - To correct chronic instability of the trapeziometacarpal joint, the authors
      reconstructs the posteromedial ligamentous complex using flaps of extensor
      retinaculum. Two small dorsal incisions allow harvesting free segments of
      extensor retinaculum detached from the proximal portion of extensor retinaculum
      to repair dorsal injuries when these prove to be superficial. When necessary, a
      clip passed via a small palmar cunter incision allows a complementary palmar
      reconstruction. For repair of anterior ligaments, the palmar incision can be
      extended and a pedicled flap derived from the retinaculum is used. There is a
      detailed description of technique and results.

PMID- 11291329
TI  - Left atrium leiomyosarcoma.

PMID- 11291330
TI  - Identification of patients most likely to benefit from implantable cardioverter
      defibrillator therapy--the Canadian Implantable Defibrillator Study.

PMID- 11291331
TI  - Cardiac rehabilitation rehabilitated in the turn of the millennium: an overall
      approach.

PMID- 11291332
TI  - Autonomic function in chronic liver disease assessed by Heart Rate Variability
      Study.
AB  - BACKGROUND: Chronic liver disease is associated with cardiovascular changes,
      including hyperdynamic circulation with increased blood volume and cardiac
      output, and with reduced peripheral vascular resistance. Autonomic dysfunction is
      a common finding in these patients, being involved in the pathogenesis of the
      hyperdynamic condition. The aim of our study was to evaluate autonomic function
      in cirrhotic patients by using the 24 hour Heart Rate Variability study. We also
      sought to relate the degree of autonomic dysfunction with the severity of the
      liver disease. MATERIAL AND METHODS: We studied 22 cirrhotic patients, 50% of
      whom were male, mean age 44.14 +/- 11.32 years. The etiology was alcohol related
      in 12 (54.6%), virus hepatitis in 6 (27.2%), autoimmune related in two (9.1%) and
      other in the remaining two (9.1%). In terms of severity liver disease 6 patients
      were in Child-Pugh's class A (27.3%), 9 in Child-Pugh's class B (40.9%) and 7 in
      Child-Pugh's class C (31.8%). Thirteen patients (59%) had ascites. Both patients
      and 20 age-sex matched healthy volunteers underwent 24 hour ECG Holter study with
      assessment of Heart Rate Variability (time and frequency domains). RESULTS: The
      cirrhotic patients showed severe decrease in Heart Rate Variability when compared
      to healthy volunteers: SDNN (84.14 +/- 35.78 ms vs 148.9 +/- 33.97 ms; p <
      0.0001), pNN50 (3.54 +/- 4.61 vs 11.17 +/- 9.88; p = 0.004). The spectral
      analysis revealed markedly decrease of average total power, with reduction of all
      components (VLF, LF, HF), in the absence of significant difference in LF/HF ratio
      (2.52 +/- 1.40 vs 2.98 +/- 1.57; p = NS). Ascites had relationship with more
      pronounced autonomic impairment: SDNN (70.31 +/- 30.32 ms vs 104.11 +/- 34.97 ms;
      p = 0.03). On the other hand, alcohol related etiology did not influence Heart
      Rate Variability parameters. Moreover, we found significant positive correlations
      between SDNN (dependent variable) and Prothrombin activity (r = 0.64; p = 0.001),
      as well as with Serum Albumin (r = 0.40; p = 0.05), but not with Total Bilirubin
      (r = -0.14; p = 0.51). Prothrombin activity was the only independent predictor of
      autonomic dysfunction. CONCLUSION: Chronic liver disease is accompanied by a
      significant Heart Rate Variability decrease. Alcohol related etiology does not
      indicate further autonomic dysfunction. The greater the hepatopathy severity, the
      greater the Heart Rate Variability impairment. Hepatocellular dysfunction
      indicators have more accuracy to demonstrate autonomic disturbances than
      cholestasis indicators.

PMID- 11291333
TI  - [Mitral flow propagation velocity assessed with M-mode color Doppler in patients
      with dilated cardiomyopathy].
AB  - BACKGROUND: The role of diastolic disfunction in the setting of severe left
      ventricular (LV) disfunction is usually forgotten due to difficulties in
      quantification and interpretation. The propagation velocity (PV) of mitral inflow
      into the left ventricle has been proposed as a load independent indicator of LV
      diastolic function. Our aim was to correlate PV with age, body surface, chambers
      dimensions, wall thickness and with classic parameters of systolic and diastolic
      function. We had in mind the validation of this index in the quantification of LV
      filling and in risk stratification of patients with dilated cardiomyopathy (DC).
      MATERIAL AND METHODS: We prospectively studied 32 consecutive patients, mean age
      56.1 +/- 15.7 years, 22 (68.75%) male, mean ejection fraction 28.1 +/- 7.5%. All
      of them were in NYHA class < or = II and on ACE inhibitors. Eight (25%) were on
      beta-blockers. Patients without sinus rhythm, paced or with significant
      hypertensive, congenital or valvular heart disease were previously excluded. The
      following parameters of LV systolic function were assessed by echocardiography:
      fractional shortening, ejection fraction and cardiac output. LV filling was
      assessed by transmitral flow pulsed Doppler analysis: isovolumic relaxation time
      (IVRT), peak E and A wave velocities, E wave deceleration time (DT). We also
      evaluated a new Doppler index of combined systolic and diastolic myocardial
      performance (Tei index). PV (cm/s) was calculated by Color M-mode. Univariate
      regression analysis was performed (PV as dependent variable). RESULTS: We
      detected a high prevalence of diastolic function disturbances: 25 (78.1%)
      patients with a delayed relaxation pattern and only 3 (9.4%) with a restrictive
      pattern. PV did not correlate with age, body surface and LV geometry. There was a
      significant correlation between PV and E/A ratio (r = 0.61; p < 0.0001), IVRT (r
      = -0.50; p = 0.006), DT (r = -0.41; p = 0.01) and Tei index (r = -0.36; p =
      0.04). CONCLUSIONS: Our results indicate that, in patients with a predominance of
      delayed relaxation, there is a strong relationship between PV and the classic
      parameters of LV filling. For similar levels of systolic impairment, PV could be
      an easy, fast and reproducible quantitative indicator of severity on DC.

PMID- 11291334
TI  - [Prognosis of postoperative aortic dissection. Assessment with magnetic
      resonance].
AB  - OBJECTIVE: To evaluate operated type A aortic dissection by Magnetic Resonance
      Imaging (MRI), in order to detect long-term complications and identify prognostic
      indexes of evolution. DESIGN: Prospective study with a three-year period of
      follow-up. Prognosis evaluation. SETTINGS: Outpatient Clinic at Hospital de Santa
      Maria and Magnetic Resonance Imaging Center at Hospital da Cruz Vermelha.
      PATIENTS: A sample of 37 patients submitted to type A aortic dissection surgery,
      included sequentially, after exclusion of those with contraindication to MRI.
      METHODS: Initial evaluation (clinical and MRI study) at 3 to 4 months and at 1, 2
      and 3 years after surgery. The mean follow-up time was 39.3 +/- 2.9 months. We
      evaluated the following complications over the aorta (aortic graft and five
      segments of residual aorta) and the aortic valve: aneurysm, pseudoaneurysm,
      rupture, re-dissection, progressive aortic valve regurgitation, reoperation and
      death. The prognostic indexes analysed were: presence of residual flap; false
      lumen patency; presence of re-entry points; false lumen to aorta dimension ratio;
      initial aortic dimension; increase of aortic dimension. RESULTS: All patients,
      with the exception of three that died, remained asymptomatic. COMPLICATIONS:
      Aneurysm was detected in 45.9% of patients, located in one or more segments;
      rupture occurred in three patients, preceded by aneurysm and pseudoaneurysm
      development; moderate or severe aortic regurgitation was detected in 47.8% of
      patients. Prognostic indexes: 1. Aneurysm development in each segment yeilded a
      significant association with: presence of residual flap in the same and other
      segments; higher initial dimension of the same and other segments, with the
      exception of the abdominal segment; higher increase in dimension of the same and
      other segments, with the exception of the abdominal segment; 2. Moderate or
      severe aortic regurgitation development showed a tendency to association with
      higher increase in dimension of proximal ascending aorta. 3. No association was
      found between aneurysm and aortic regurgitation development. CONCLUSIONS:
      Patients operated for type A aortic dissection had a high incidence of late
      complications which lead to reoperation and in some cases death. The presence of
      a residual flap, increased aortic dimensions and higher increase rate of aortic
      dimensions were associated with a complicated evolution. MRI was a very useful
      technique for long-term monitoring and to identify prognostic indexes of
      evolution.

PMID- 11291335
TI  - [Interaction between load and beta-adrenergic stimulation in the modulation of
      diastolic function].
AB  - INTRODUCTION AND OBJECTIVES: Excessive afterload induces an upward shift of the
      diastolic pressure-volume relation. This diastolic dysfunction was attributed to
      the concomitant slowing of relaxation. The present study investigated to what
      extent beta-adrenergic stimulation could influence this effect. METHODS: Beat-to
      beat afterload elevations were induced in anaesthetised open-chest rabbits (n =
      7) by narrowing the ascending aorta, to increase peak left ventricular pressure
      (LVPmax) from control up to isovolumetric. Afterload elevations were performed at
      baseline and during infusion of isoproterenol (0.15 mg/kg/min). RESULTS: At
      baseline, LVPmax increased from 84 +/- 7 in the control beat to 154 +/- 10 mmHg
      in the isovolumetric beat, while during isoproterenol it increased from 88 +/- 4
      to 184 +/- 11 mmHg (p < 0.01). After an isovolumetric beat, diastolic dysfunction
      was 7.9 +/- 1.5 mmHg at baseline and 2.6 +/- 0.5 mmHg during isoproterenol (p <
      0.01). At all afterload levels, isoproterenol accelerated LVP fall (decreased the
      time constant tau), decreased the predicted time to completion of relaxation but
      did not influence the time available for the ventricle to relax. CONCLUSIONS AND
      IMPLICATIONS: Afterload induced diastolic dysfunction was attenuated by beta
      adrenergic stimulation. These results, along with the inotropic and lusitropic
      effects of isoproterenol, may contribute to the acute improvement of cardiac
      function induced by beta-adrenergic stimulation. It may also help to explain the
      response to physical exercise and the pathophysiology of diastolic dysfunction in
      heart failure.

PMID- 11291336
TI  - [Recurrent pericardial effusion --a case of cardiac angiosarcoma].
AB  - A case of angiosarcoma of the right atrium in a 59-year-old woman is reported,
      presenting as a recurrent hematic pericardial effusion. The usefulness of
      echocardiography in making the diagnosis is emphasized. The tumor was already
      disseminated at the time of the diagnosis. The patient was on palliative therapy,
      dying a few months later. The histological examination was done at autopsy. This
      case highlights the difficulty in diagnosis and the various modalities available
      for an accurate diagnosis of a rare clinical entity. It has a rapid and
      aggressive course with a very poor prognosis.

PMID- 11291337
TI  - National survey of cardiac rehabilitation programs in Portugal--situation in
      1999.
AB  - In order to study the status of Cardiac Rehabilitation (CR) in Portugal in 1998
      and 1999, a questionnaire was drafted and sent to all the heads of the CR centres
      in Portugal, with questions about their nature, location, staff, type of
      activity, movement, diagnosis leading to patient referral and funding. The rate
      of coronary patients admitted to the programs existing in the cities of Lisbon
      and Oporto was calculated. The total number of patients included in all the CR
      centres in both cities was subtracted from the total number of public hospital
      discharges of coronary patients in 1998, patients admitted due to acute ischaemic
      coronary syndrome or for revascularization in Portugal and in each of the two
      cities. We found that there were CR centres in only the two main cities (Lisbon
      and Oporto), with organization and types of activity in accordance with
      international guidelines and recommendations. The overall admission rate of
      coronary patients in Portugal in 1998 was 0.7%, with 0.9% and 1.9% in Lisbon and
      Oporto, respectively. These rates are well below the figures for countries of the
      European Union and for the USA. It is very important to increase the
      establishment and spread of CR centres throughout the country, creating the
      financial conditions and promoting a change in culture regarding physical
      activity and CR on the part of the Portuguese population, patients and health
      care providers responsible for the referral of cardiac patients to a therapeutic
      intervention that can increase quality of life and longevity. Doctors should be
      involved in programs that will train them to recognize the benefits of physical
      activity and secondary prevention.

PMID- 11291338
TI  - Acute type A aortic dissection involving the left main coronary artery and the
      aortic valve--a case report.
AB  - The authors report a case study of a 60 year-old-male admitted to the Coronary
      Care Unit with severe chest pain, hypertension and ST depression on the anterior
      and lateral leads of the electrocardiogram. A diastolic murmur was heard in the
      aortic area. The chest X-ray showed an enlarged superior mediastinum. The
      transthoracic echocardiogram revealed an image that indicated an intimal flap
      above the aortic plane with severe aortic regurgitation. An aortography was
      performed and confirmed the diagnosis of acute type A aortic dissection with
      partial obstruction of the left main coronary artery, probably due to compression
      by the haematoma. The patient underwent emergency surgical repair with
      replacement of the aortic valve and ascending aorta. The patient survived without
      complications post surgery and was discharged ten days after onset of symptoms.
      Twenty months later, the patient was asymptomatic and the transesophageal
      echocardiogram showed a dissection of the descending thoracic aorta, mild aortic
      regurgitation and good left ventricular systolic function.

PMID- 11291339
TI  - [Update on the treatment with platelet antiaggregation agents].
AB  - Antiplatelet agents are primarily used to prevent and treat arterial thrombosis.
      Their mechanism of action is related to the interaction with metabolism of
      arachidonic acid, the increase of intraplatelet cAMP or the antagonism of ADP or
      GP IIb/IIIa receptors. Aspirin was one of the first agents to be adopted and it
      remains as the standard therapy with the higher amount of available clinical
      information. Following aspirin, ADP receptor antagonists like ticlopidine and
      more recently clopidogrel have been introduced. In the CAPRIE study, clopidogrel
      was shown to be more effective than aspirin in the prevention of vascular events
      in patients with atherothrombotic disease. The newer antiplatelet agents are GP
      IIb/IIIa receptor antagonists like eptifibatide, tirofiban and abciximab, which
      act at the end of the common pathway of platelet aggregation. Their benefits
      after intravenous administration have been shown in the treatment of acute
      coronary syndrome and percutaneous coronary angioplasty. The potential
      application of GIIb/IIIa targeted therapy might theortically be expanded by the
      new class of oral GP IIb/IIIa antagonists. However, their performance in clinical
      trials has been disappointing.

PMID- 11291340
TI  - [Glossary of terms and concepts used in scientific evidence based cardiology.
      Part I: diagnosis, therapy, iatrogenesis, generalities].
AB  - The papers published by the Revista about Evidence-Based Cardiology (EBC) have,
      so far, discussed general aspects of the theory as well as practice of EBC, using
      simple terms. We need a detailed description of the general, as well as specific,
      concepts applicable to EBC, in order to understand this methodology better and to
      facilitate the reading. In this first article we present a glossary of terms
      applicable to general aspects of the methodology, including terms found in papers
      about diagnosis, treatment, risk/harm, etc. A second paper, to be published in
      the next issue of the Revista, will present concepts regarding clinical trials
      (types, methodology, etc.) and systematic reviews.

PMID- 11291341
TI  - The influence of dressings on the healing of normal and ischaemic wounds and flap
      survival.
AB  - The effects of dressing with Duoderm (occlusive hydrocolloid) and Mepore
      (permeable viscose) on the healing of normal and ischaemic incisional wounds, and
      on flap survival, were investigated in 60 rats. The biomechanical properties of
      dressed normal wounds after 14 days did not differ from those of the undressed
      controls. In contrast, energies at maximum and breaking (load*S, stress*S) of
      dressed ischaemic wounds decreased by 30%-42% after 14 days of healing, compared
      with undressed ischaemic controls. Dressing decreased the shrinkage of ischaemic
      wounds and necrosis length of ischaemic flaps. Normal incisional wounds can
      safely be dressed for 14 days without the wound strength being affected.
      Dressings may be useful clinically in preventing superficial dermal necroses. One
      must, however, be aware of the impairment of the wound strength of ischaemic
      incisional wounds.

PMID- 11291342
TI  - Cutaneous metastasis from small cell lung carcinoma. Case report.
AB  - We report a rare case of cutaneous metastatic small cell lung carcinoma of the
      upper lip in a 73-year-old man, which was excised and the defect repaired with a
      single advancement flap from the cheek. The prognosis of such lesions is poor,
      and the incidence of other metastases elsewhere is high. The aim of treatment was
      to give him optimal quality of life for the short time left. The patient died of
      his primary disease four months later.

PMID- 11291343
TI  - Treatment of Setleis syndrome. Case report.
AB  - Setleis syndrome is characterised by a leonine appearance. We have treated an 8
      year-old boy with the syndrome and describe the plastic surgical procedures done
      and the histological findings.

PMID- 11291344
TI  - Changes in nitric oxide, superoxide, and blood circulation in muscles over time
      after warm ischaemic reperfusion in rabbit rectus femoris muscle.
AB  - We present the sequence of changes in nitric oxide (NO) and superoxide (O2-) over
      time in reperfusion injuries. We examined both the changes in NO and O2- over
      time and the blood flow in an isolated ischaemia-reperfusion muscle model in
      rabbits. The ischaemic group comprised 8 animals which had had vascular pedicles
      clamped on the their rectus femoris muscles for 4 hours. The control group (n =
      6) had a sham operation. Blood samples from the femoral vein proximal to the
      clamping point were collected before the operation, before clamping, before
      reperfusion, immediately after reperfusion, and 5, 15, 30, 60, and 120 minutes
      after reperfusion. NO was measured by Griess' method, and O2- by
      chemiluminescence. Blood flow was measured with a laser Doppler flowmeter. The
      amount of NO increased significantly immediately after reperfusion, and 15 and 30
      minutes after reperfusion in the ischaemic group, compared with the control group
      (p < 0.05). O2- increased significantly at 5, 15, 60, 90 and 120 minutes after
      reperfusion, compared with the control group (p < 0.05). The blood flow volume
      curve increased by 1.4 times about four minutes after reperfusion compared with
      previously. After this it gradually decreased. The adverse effects of O2- became
      apparent when NO was extinguished by O2-.

PMID- 11291345
TI  - The effect of dipyrone on survival of skin flaps.
AB  - The effect of dipyrone on the skin flap survival was studied in a model of an
      epigastric island flap with a random extension on the opposite side in 23 rats.
      Dipyrone was given intraperitoneally one hour before the skin flap was raised. At
      the end of the operation the depth of penetration of the fluorescein dye in the
      skin flap was assessed visually from photographic records and the flap survival
      area was measured by a grid method on the seventh postoperative day. There was a
      significant reduction in the amount of ischaemic necrosis of the skin flap after
      a single dose of dipyrone 50 mg/kg (p < 0.001). These data suggest that dipyrone
      is a useful agent in the prevention and treatment of ischaemia and necrosis of
      the skin flap.

PMID- 11291346
TI  - Expanded polytetrafluoroethylene as tendon replacement: an experimental study in
      chickens.
AB  - We designed an experimental animal model (in chickens) to assess the potential
      applications, above all in hand surgery, of an expanded polytetrafluoroethylene
      (e-PTFE) graft as a replacement for a natural tendon. The results of macroscopic,
      histological, and functional observations made five weeks, and three, four, five,
      and six months after implantation showed that the e-PTFE seemed to be a good
      replacement for tendons, because it integrated well with surrounding tissue and
      permitted good functional recovery within a reasonable time period.

PMID- 11291347
TI  - Tissue response to silicone tubes used to repair human median and ulnar nerves.
AB  - Silicone tubes of appropriate sizes were used to enclose the injured zone of
      transsected ulnar and median nerves in the human forearm as an alternative to
      conventional microsurgical repair of the nerve trunk. A gap measuring 3-5 mm was
      left intentionally between the nerve ends inside the tube. The clinical early
      results from a prospective randomised study that compared these two principles
      have recently been presented. Seven patients (five men and two women), aged 15-49
      years (median 20) were reexplored 12-44 months (median 22) after the initial
      procedure because of local discomfort from the tube in four patients. There was a
      new nerve structure bridging the former gap and in most cases it was impossible
      to distinguish the site of the injury. In all cases there was a thin capsule
      around the silicone tube that microscopically consisted of connective tissue with
      thin walls and no signs of inflammation, granuloma or macrophages (n = 4), while
      in two cases a mild foreign body reaction was seen at a single site (n = 1) or at
      patchy areas (n = 1). These results indicate that after more than one year there
      is a limited tissue reaction around silicone tubes used to repair median and
      ulnar nerves in humans.

PMID- 11291348
TI  - Tibia as donor site for alveolar bone grafting in patients with cleft lip and
      palate: long-term experience.
AB  - Tibial bone grafts were studied in 137 patients with clefts of the lip and
      palate. Twenty-one had clefts of the lip and primary palate and 116 had complete
      unilateral clefts of the lip and palate. Bone grafting was performed secondarily
      or late secondarily. Bone was harvested from the proximal part of the tibia
      distal to the tuberosity through an incision about 15 mm long. The mean follow-up
      time after bone grafting was 5.5 years (range 2-11). There were no operative, or
      early or late postoperative complications reported (such as haematoma, fracture,
      or shortening of the limb). Harvesting time was about 15 minutes. The possibility
      of operating with two teams makes the total operating time shorter. Bleeding was
      negligible (less than 15 ml) and the amount of bone obtained was always
      sufficient. Patients were mobilised the next day and were back to full physical
      activity by one month. Indications for tibial bone grafting included facilitation
      of tooth eruption into the graft, giving bony support to the neighbouring teeth,
      making it possible to insert a titanium fixture, raising the alar base of the
      nose, and closing an oronasal fistula. Compared with iliac, cranial, mandibular,
      and costal donor sites, using the tibia took less time, gave less bleeding, made
      it possible for two teams to operate simultaneously, gave a smaller scar, and
      there were minimal complications and satisfactory quantity and quality of bone in
      all cases. The results suggested that the tibia is an excellent choice of graft
      for residual alveolar clefts in patients with cleft lip and palate.

PMID- 11291349
TI  - Skeletal stability of Le Fort I osteotomy in patients with unilateral cleft lip
      and palate.
AB  - The skeletal stability of Le Fort I osteotomy was evaluated cephalometrically in
      40 consecutive patients with unilateral cleft lip and palate (UCLP) (27 male and
      13 female) who were operated on between 1987-1995. Their mean age at the time of
      operation was 23.7 years (range 16.3-40.4). The one-piece Le Fort I osteotomy was
      fixed with titanium plates and the osteotomy line was bone-grafted. Neither
      intermaxillary fixation nor occlusal splints were used postoperatively. Skeletal
      stability was analysed both horizontally and vertically on cephalograms taken
      shortly before operation, immediately afterwards, and at six months and at one
      year postoperatively. The mean maxillary advancement (point A) during the Le Fort
      I was 3.9 mm (range 0-8.9) and mean vertical lengthening 4.5 mm (range -0.6
      10.5). One year postoperatively the mean maxillary horizontal relapse was 20.5%
      (0.8 mm, range 0-3.7) whereas the mean vertical relapse was 22.2% (1 mm, range 0
      5.7). The vertical relapse reduced from 38% to 8.3% between 1987 and 1995, and
      there was a positive correlation between the amount of maxillary advancement and
      relapse both horizontally and vertically.

PMID- 11291350
TI  - Endoscopic forehead lift for ptosis of the brow caused by facial paralysis.
AB  - Twelve patients with ptosis of the brow caused by facial nerve paralysis were
      treated by endoscopic forehead lift. Four had an isolated paralysis of the
      temporal branch of the facial nerve and in eight the entire facial nerve was
      affected. In two of these patients the facial paralysis was bilateral, caused by
      Finnish hereditary amyloidosis. A standard subperiosteal endoforehead approach
      was used and the forehead was fixed by biodegradable pins (n = 8), anchor screws
      (n = 3), or a suture to the posterior scalp (n = 1). The procedure was a success
      in 10 patients, and failed in two after initially good results. The endoscopic
      brow lift is a good method of treating ptosis of the brow caused by paralysis of
      the temporal branch of the facial nerve.

PMID- 11291352
TI  - Silastic implant for reconstruction of pectus excavatum: an update.
AB  - Twenty-seven patients were operated on for pectus excavatum between 1985 and 1996
      and had a custom-made subcutaneous Silastic implant inserted. We have reviewed
      their medical records to evaluate the clinical course, and used a questionnaire
      to assess the subjective outcome. There were no major surgical complications.
      Sixteen of the 27 patients reported improved appearance, and 11 would definitely
      recommend the operation to other patients under similar circumstances. Increased
      familiarity with the technique has led to implants with better size and shape,
      shorter hospital stay, and also to patients being more confident with the
      outcome. Augmentation with a custom-made Silastic implant is still a simple and
      straightforward way of concealing the deformity and alleviating the subjective
      discomfort in patients with pectus excavatum, whose cardiopulmonary function is
      within the normal range.

PMID- 11291351
TI  - Effects of continuous stretching on cell proliferation and collagen synthesis in
      human burn scars.
AB  - Hypertrophic and contracted scars are common complications of deep and partial
      thickness burns, and the usual way to prevent them is to stretch the burn are
      actively as well as passively. However, little has been written about the effects
      of stretching on burn scar tissue at a cellular and molecular level. The
      stretching usually results in an increased area of skin, and a central question
      is whether this is caused by stimulation of cell proliferation or decreased cell
      density, which could lead to impaired quality of the skin. In the present study a
      new in vitro model was developed and used to study the effects of stretching on
      the proliferative activity as well as on the synthesis of collagen in human burn
      scars. Proliferation was measured quantitatively by thymidine incorporation and
      spatially by immunohistochemistry. The net proliferation in the burn scar was
      decreased after one day, and significantly decreased after six days of continuous
      stretching (p = 0.02). However, immunohistochemistry showed increased
      proliferation in the basal layer of the epidermis while the proliferative
      activity in the dermal cells was inhibited. Collagen synthesis was decreased
      after six days of stretching whereas no effect was shown after one day. These
      findings indicate that static stretching of a human burn scar results in
      inhibition of proliferation in dermal cells leading to a low cell density in the
      dermis which, combined with increased collagen synthesis, could lead to reduced
      biomechanical strength.

PMID- 11291353
TI  - Effects of hyperbaric oxygen treatment on axonal outgrowth in sciatic nerve
      grafts in rats.
AB  - We studied the effect of hyperbaric oxygen treatment on axonal outgrowth in
      grafts of sciatic nerves in 40 rats. The sciatic nerve was transsected and a 10
      mm long segment from the opposite side was immediately sutured in as a nerve
      graft. Postoperatively 17 animals were treated with 100% oxygen at 3.2
      atmospheres absolute pressure for 45 minutes and the treatment was repeated at
      four and eight hours postoperatively and then every eight hours until evaluation.
      At seven days the axonal outgrowth was evaluated by immunohistochemical staining
      of neurofilaments in the nerve grafts. The axonal outgrowth was significantly
      longer in animals treated with hyperbaric oxygen. We conclude that hyperbaric
      oxygen can improve nerve regeneration in sciatic nerve grafts in rats.

PMID- 11291355
TI  - Long-term results after arthroscopic resection of lesions of the triangular
      fibrocartilage complex.
AB  - Thirty-five patients with central and radial lesions of the triangular
      fibrocartilage complex (TFCC) were treated by arthroscopic resection and
      debridement. Their median age was 36 years (range 11-52), and preoperative
      duration of symptoms 18 months (range 4-132). Fall on a hyperextended wrist was
      the most common injury (n = 15), and nine patients had had a previous fracture of
      the radius. Eighteen patients had an additional arthroscopic debridement of
      coexisting chondral lesions. There were no complications. At a median follow up
      time of 39 months (range 18-58), grip strength was recorded as a median of 94%
      (range 4-164), flexion-extension sector as 94% (range 50-107), and pronation and
      supination sector as 100% (range 50-112) of the uninjured side. At follow up
      eight patients were free of pain, 14 much better, eight somewhat better, five
      unchanged, and no patient had got worse. The Mayo Modified Wrist Score assessed
      13 patients as excellent, 14 good, four fair, and one poor. Thirty-one patients
      returned to full-time work, and four were unemployed (partly because of reasons
      not relevant to the operation). Thirty-three patients reported they would have
      had the same procedure if they had known the outcome of the surgery. We find
      arthroscopic debridement of central or radial lesions of the TFCC to be safe and
      reliable with good pain relief.

PMID- 11291354
TI  - Management of wounds of exposed or infected knee prostheses.
AB  - Skin damage after total knee arthroplasty may jeopardise the functional benefit
      of the prosthesis. In such cases standard treatment is aimed at avoiding
      arthrodesis, sometimes replacing the implant and, in exceptional cases,
      amputation. In most cases early and adequate coverage of the soft tissue defect
      may make it possible to salvage the prosthesis. Ten patients with skin damage
      after total knee arthroplasty were treated by debridement of the wound, which was
      then covered with a pedicled gastrocnemius muscle flap. This was supported by
      local irrigation and systemic antibiotics. Seven patients were reviewed after a
      mean follow-up of 28 months (range 14-59). Six patients kept their prostheses and
      one had a relapse caused by infection at 22 months, which required removal of the
      prosthesis and secondary arthrodesis. The gastrocnemius muscle flap provides good
      quality coverage, permits early mobilisation and fast rehabilitation, and reduces
      the rate of arthrodesis after failure of total knee arthroplasty.

PMID- 11291356
TI  - Anatomical attachments to the proximal phalangeal base--a case for stability.
AB  - Transverse midshaft fractures of the proximal phalanx are often unstable and
      require open reduction and internal fixation. In contrast, fractures of the base
      of the proximal phalanx are occasionally amenable to conservative treatment in
      the form of manipulation and a graded mobilisation programme. This stability may
      be the result of splinting of the fracture by the surrounding anatomical
      structures, but to our knowledge this has not been previously elucidated
      anatomically. In this study we define the extent of attachment of the various
      anatomical structures to the base of the proximal phalanx. The contribution of
      the joint capsule, collateral ligaments, accessory collateral ligaments,
      interosseous muscles, and volar (palmar) plate may confer stability to fractures
      in the proximal 6-9 mm range at the base of the proximal phalanx, once they are
      reduced and immobilised in the correct positions.

PMID- 11291358
TI  - Scrotal reconstruction with a thinned flap based on both inferior epigastric
      arteries. Case report.
AB  - A 62-year-old man presented with an extensive defect of the scrotum caused by
      Fournier's gangrene. We reconstructed the scrotum using a thinned flap based on
      both inferior epigastric arteries one month after the first debridement. This
      method has the advantage of achieving adequate mobility of the reconstructed
      scrotum. The results were satisfactory both functionally and cosmetically,
      although we had to repair a hernia at the donor site a year later.

PMID- 11291357
TI  - Acute postoperative swelling after hand surgery: an exploratory, double-blind,
      randomised study with paracetamol, naproxen, and placebo.
AB  - A model using volumetry to evaluate the effect of drugs on acute postoperative
      swelling after operations for primary Dupuytren's contracture (DC) and carpal
      tunnel syndrome (CTS) was established and validated. The temperature of the
      saline and time of measurement during the day influenced the volumetric readings.
      The error of measurement after volumetry of unoperated and operated hands after
      operations for DC was 0.7% and 0.6%, respectively. Naproxen (500 mg twice a day),
      paracetamol (1000 mg four times a day), or placebo were given postoperatively for
      three days to 35 patients after DC and 42 patients after CTS in a randomised,
      placebo-controlled study. Hand volume was measured preoperatively and 72 hours
      after surgery. There was a difference in swelling (p = 0.009) indicating
      different degree of development of swelling 72 hours postoperatively between the
      DC and CTS placebo groups, which invalidated pooling of the data. After
      operations for DC naproxen was slightly but not significantly superior to
      paracetamol and placebo, with paracetamol numerically superior to placebo. The
      power of the study, caused by the limited number of patients included, does not
      permit this difference to reach significance. Operations for CTS caused so little
      swelling that comparisons were invalidated. Naproxen treatment, irrespective of
      type of operation, did not require rescue analgesics, while two patients after
      CTS treated with paracetamol did. Two and six placebo-treated patients required
      rescue drugs after operations for DC and CTS, respectively. We conclude that
      naproxen might have a clinical relevant effect on swelling when used on minor
      surgery in the hand, unlike paracetamol. Naproxen might be a useful analgesic
      during the immediate postoperative phase.

PMID- 11291359
TI  - Musculoskeletal manifestations of thyroid disease.

PMID- 11291360
TI  - Bioprocessing to generate 'multifunctional' foods?

PMID- 11291361
TI  - Minding the world's health: World Health Day 2001.

PMID- 11291362
TI  - Donora, Pennsylvania: an environmental disaster of the 20th century.

PMID- 11291363
TI  - Who's afraid of the truth?
AB  - The November 1998 Master Settlement Agreement between tobacco manufacturers and
      state attorneys general significantly restricted the marketing of tobacco
      products, made possible markedly expanded tobacco control programs in the states,
      and provided for the creation of a new foundation whose primary purpose is to
      combat tobacco use in the United States. This commentary describes the American
      Legacy Foundation, with particular emphasis on one of its efforts--the "truth"
      Campaign, a countermarketing effort to reduce smoking among youths. The "truth"
      Campaign has been well received by the public and is expected to be [corrected]
      effective in reducing smoking among youths. The only negative reaction to the
      campaign has been, predictably, from the tobacco industry.

PMID- 11291364
TI  - Earth Day plus 30 years: public concern and support for environmental health.
AB  - A clear majority of Americans are concerned about environmental threats to public
      health and do not want to weaken antipollution regulations. The strongest
      supporters for maintaining environmental regulations are affluent mainstream
      White suburban populations who are thriving economically, but support is also
      strong in every other major segment of the population. Overt attempts to weaken
      the basic regulations are unlikely, barring an obvious economic downturn that
      would cause a large proportion of the public to consider loosening standards in
      the belief that such changes would increase the number of available jobs. Given
      this context, environmental health was and will continue to be a core topic in
      the Journal. We will emphasize the nexus of environmental health and policy by
      publishing research, exemplary public health practice, and the views of key
      decision makers.

PMID- 11291365
TI  - Environmental exposures and childhood cancer: our best may not be good enough.

PMID- 11291366
TI  - Household solvent exposures and childhood acute lymphoblastic leukemia.
AB  - OBJECTIVES: This study explored the risk of childhood acute lymphoblastic
      leukemia (ALL) associated with participation by household members in hobbies or
      other home projects involving organic solvents. METHODS: Participants in this
      case-control study were 640 subjects with ALL and 640 matched controls. RESULTS:
      Childhood ALL was associated with frequent (> 4 times/month) exposure to model
      building (odds ratio [OR] = 1.9; 95% confidence interval [95% CI] = 0.7, 5.8) and
      artwork using solvents (OR = 4.1; 95% CI = 1.1, 15.1). We also found elevated
      risk (OR = 1.7; 95% CI = 1.1, 2.7) among children whose mothers lived in homes
      painted extensively (> 4 rooms) in the year before the children's birth.
      CONCLUSIONS: In this exploratory study, substantial participation by household
      members in some common household activities that involve organic solvents was
      associated with elevated risks of childhood ALL.

PMID- 11291367
TI  - Environmental health training of promotoras in colonias along the Texas-Mexico
      border.
AB  - Poverty, overpopulation, and a lack of environmental controls have combined with
      cultural and linguistic division to produce a looming public health threat in
      unincorporated communities on the US-Mexico border. These rapidly multiplying
      colonias, from a Spanish term for neighborhoods, are settlements of varying size
      located along the border. Along the American side of the Texas-Mexico border
      alone, there are approximately 1800 colonias--the largest number of any border
      state--most of which lack basic water and sewer systems, paved roads, and safe
      and sanitary housing. Promotoras, from a Spanish term for lay community
      educators, are community leaders who live in the colonias and build important
      bridges between residents and the federal and state bureaucracies. These women
      have been trained to introduce their neighbors to state "systems" of government,
      education, and medical and social services that otherwise may lie out of reach.
      Promotoras are able to "translate" this training into culturally meaningful
      instruction that empowers community self-development. When neighbors teach
      neighbors, the message is received with greater trust and readiness to act.

PMID- 11291368
TI  - Effects of air pollution on blood pressure: a population-based approach.
AB  - OBJECTIVES: This analysis assessed the association between blood pressure,
      meteorology, and air pollution in a random population sample. METHODS: Blood
      pressure measurements of 2607 men and women aged 25 to 64 years who participated
      in the Augsburg Monitoring of Trends and Determinants in Cardiovascular Disease
      survey were analyzed in association with 24-hour mean concentrations of air
      pollutants. RESULTS: During the air pollution episode in Europe in January 1985,
      an association between blood pressure and air pollution was observed, which
      disappeared after adjustment for meteorology. Continuous concentrations of total
      suspended particulates and sulfur dioxide were associated with an increase in
      systolic blood pressure of 1.79 mm Hg (95% confidence interval [CI] = 0.63, 2.95)
      per 90 micrograms/m3 total suspended particulates and 0.74 mm Hg (95% CI = 0.08,
      1.40) per 80 micrograms/m3 sulfur dioxide. In subgroups with high plasma
      viscosity levels and increased heart rates, systolic blood pressure increased by
      6.93 mm Hg (95% CI = 4.31, 9.75) and 7.76 mm Hg (95% CI = 5.70, 9.82) in
      association with total suspended particulates. CONCLUSIONS: The observed increase
      in systolic blood pressure associated with ambient air pollution could be related
      to a change in cardiovascular autonomic control.

PMID- 11291369
TI  - Physical activity and mortality: a prospective study among women.
AB  - OBJECTIVES: This study examined the association between recreational physical
      activity and mortality in middle-aged and older women and the possibility that
      physical activity serves as an important marker of health. METHODS: Analyses were
      conducted among participants in the Nurses' Health Study. Levels of physical
      activity were assessed by questionnaire in 1980 and updated every 2 to 4 years.
      RESULTS: Levels of physical activity were inversely associated with mortality
      risk; however, each activity level above the reference level had approximately
      the same level of risk reduction (20%-30%). The inverse association was stronger
      for cardiovascular deaths than for cancer deaths and was strongest for
      respiratory deaths. Women who died of noncardiovascular, noncancer causes were
      more likely to have reported that poor health limited their physical activity
      than were women who died of other causes or who remained alive. CONCLUSIONS: Part
      of the link between physical activity and mortality risk is probably spurious and
      difficult to remove analytically; however, on the basis of epidemiologic
      evidence, much of the health benefit of activity is real.

PMID- 11291370
TI  - Promoting breast and cervical cancer screening at the workplace: results from the
      Woman to Woman Study.
AB  - OBJECTIVES: This article reports findings from a peer-delivered intervention
      designed to increase use of breast and cervical cancer screening. METHODS: Twenty
      six worksites were randomly assigned to the intervention or comparison group. The
      16-month intervention consisted of group discussions, outreach, and educational
      campaigns. Data were collected from a random sample of women employees stratified
      by age (baseline n = 2943; final n = 2747). Cross-sectional analyses were
      conducted to evaluate the impact of the intervention on screening behaviors.
      RESULTS: Relative to comparison worksites, the intervention group experienced
      greater increases in the percentage of women who reported a recent mammogram
      (7.2% vs 5.6%), clinical breast examination (5.8% vs 2.1%), and Papanicolaou
      (Pap) test (4.7% vs 1.9%). After worksite cluster and age strata were controlled
      for, the observed increase in Pap tests was significantly greater in the
      intervention group (odds ratio [OR] = 1.28; 95% confidence interval [CI] = 1.01,
      1.62); however, differences in mammography screening rates (OR = 1.14; 95% CI =
      0.90, 1.44) and clinical breast examination (OR = 1.19; 95% CI = 0.96, 1.49) were
      not statistically significant. CONCLUSIONS: Intervention activities produced a
      modest increase in cervical cancer screening, but they did not accelerate breast
      cancer screening rates above the observed secular trend.

PMID- 11291372
TI  - Strange bedfellows: the history of collaboration between the Massachusetts
      Restaurant Association and the tobacco industry.
AB  - OBJECTIVES: This article examines the historical relationship between the tobacco
      industry and the Massachusetts Restaurant Association, a nonprofit trade
      association aligned with the food and beverage industry. METHODS: The study
      analyzed data from Web-based tobacco industry documents, public relations
      materials, news articles, testimony from public hearings, requests for
      injunctions, court decisions, economic impact studies, handbooks, and private
      correspondence. RESULTS: Tobacco industry documents that became public after
      various state lawsuits reveal that a long history of collaboration exists between
      the Massachusetts Restaurant Association and the tobacco industry. For more than
      20 years, their joint efforts have focused primarily on the battle to defeat
      state and local laws that would restrict smoking in public places, particularly
      in beverage and food service establishments. The resources of the tobacco
      industry, combined with the association's grassroots mobilization of its
      membership, have fueled their opposition to many state and local smoke-free
      restaurant, bar, and workplace laws in Massachusetts. CONCLUSIONS: The universal
      opposition of the Massachusetts Restaurant Association to smoking bans in food
      and beverage establishments is a reflection of its historic relationship with the
      tobacco industry.

PMID- 11291371
TI  - Cancer-related risk indicators and preventive screening behaviors among lesbians
      and bisexual women.
AB  - OBJECTIVES: This study examined whether lesbians are at increased risk for
      certain cancers as a result of an accumulation of behavioral risk factors and
      difficulties in accessing health care. METHODS: Prevalence estimates of
      behavioral risk factors (nulliparity, obesity, smoking, and alcohol use), cancer
      screening behaviors, and self-reported breast cancer histories derived from 7
      independently conducted surveys of lesbians/bisexual women (n = 11,876) were
      compared with national estimates for women. RESULTS: In comparison with adjusted
      estimates for the US female population, lesbians/bisexual women exhibited greater
      prevalence rates of obesity, alcohol use, and tobacco use and lower rates of
      parity and birth control pill use. These women were also less likely to have
      health insurance coverage or to have had a recent pelvic examination or
      mammogram. Self-reported histories of breast cancer, however, did not differ from
      adjusted US female population estimates. CONCLUSIONS: Lesbians and bisexual women
      differ from heterosexual women in patterns of health risk. These women would be
      expected to be at especially greater risk for chronic diseases linked to smoking
      and obesity.

PMID- 11291373
TI  - The influence of a family program on adolescent tobacco and alcohol use.
AB  - OBJECTIVES: This study examined a family-directed program's effectiveness in
      preventing adolescent tobacco and alcohol use in a general population. METHODS:
      Adolescents aged 12 to 14 years and their families were identified by random
      digit dialing throughout the contiguous United States. After providing baseline
      data by telephone interviews, they were randomly allocated to receive or not
      receive a family-directed program featuring mailed booklets and telephone
      contacts by health educators. Follow-up telephone interviews were conducted 3 and
      12 months after program completion. RESULTS: The findings suggested that smoking
      onset was reduced by 16.4% at 1 year, with a 25.0% reduction for non-Hispanic
      Whites but no statistically significant program effect for other
      races/ethnicities. There were no statistically significant program effects for
      smokeless tobacco or alcohol use onset. CONCLUSIONS: The family-directed program
      was associated with reduced smoking onset for non-Hispanic Whites, suggesting
      that it is worthy of further application, development, and evaluation.

PMID- 11291374
TI  - Privatization and the scope of public health: a national survey of local health
      department directors.
AB  - OBJECTIVES: This study sought to obtain and analyze nationally representative
      data on (1) privatization of local health department services, (2) local health
      department directors' beliefs and perspectives on the desirable role and focus of
      health departments, and (3) the influence of these views on privatization
      practices. METHODS: A stratified representative national sample of 380 local
      health department directors was drawn, and 347 directors were interviewed by
      telephone. Logistic regression established the independent effects of various
      factors on decisions to privatize. RESULTS: Almost three quarters (73%) of the
      local health departments privatized public health services of some type. The 12%
      of the directors who believed that local health departments should be restricted
      to the core public health functions and move entirely out of direct provision of
      personal health care were more likely to privatize services. The 77% of the
      directors who believed that local health departments should be involved in an
      increasing array of social problems were more likely to privatize. CONCLUSIONS:
      Privatization has quietly and quickly become commonplace in public health, and
      privatization practices are intimately related to divergent conceptions of public
      health and the role of local health departments.

PMID- 11291375
TI  - The association of school environments with youth physical activity.
AB  - OBJECTIVES: This study assessed the association of school environmental
      characteristics with student physical activity on campus. METHODS: Physical
      activity areas (n = 137) at 24 public middle schools were assessed for area type,
      size, and improvements (e.g., basketball courts). Student physical activity and
      the presence of equipment and supervision were directly observed before school,
      after lunch, and after school. RESULTS: Environmental characteristics explained
      42% of the variance in the proportion of girls who were physically active and 59%
      of the variance for boys. CONCLUSIONS: School environments with high levels of
      supervision and improvements stimulated girls and boys to be more physically
      active.

PMID- 11291376
TI  - The effectiveness of housing policies in reducing children's lead exposure.
AB  - OBJECTIVES: This study evaluated the relation of housing policies to risk of
      subsequent lead exposure in addresses where lead-poisoned children had lived.
      METHODS: Addresses where children with lead poisoning lived between May 1992 and
      April 1993 were selected from lead screening registries in 2 northeastern states
      differing in their enforcement of lead poisoning prevention statutes. Blood lead
      levels of subsequently resident children, exterior condition, tax value, age, and
      census tract characteristics were collected. The odds of elevated blood lead
      levels in subsequently resident children were calculated with logistic
      regression. RESULTS: The risk of identifying 1 or more children with blood lead
      levels of 10 micrograms/dL or greater was 4 times higher in addresses with
      limited enforcement. Controlling for major confounders had little effect on the
      estimate. CONCLUSIONS: Enforcement of housing policies interrupts the cycle of
      repeated lead exposure.

PMID- 11291377
TI  - Discovering unrecognized lead-smelting sites by historical methods.
AB  - OBJECTIVES: Our objective was to enumerate unrecognized former lead smelters in
      the United States. METHODS: Defunct smelters were identified by historical
      research. The compiled list was compared with government registries of hazardous
      sites. Soil samples were taken from 10 sites. RESULTS: Approximately 430 sites
      were unknown to the federal authorities. Only 5 of 319 sites were known to
      authorities in the top 8 states. Nine of the 10 sites sampled exceeded
      residential standards for soil lead level. CONCLUSIONS: Approximately 430 former
      lead-smelting sites were unrecognized in the United States. Sampling results
      indicate that the sites may pose a threat to public health.

PMID- 11291378
TI  - Crash and injury reduction following installation of roundabouts in the United
      States.
AB  - OBJECTIVES: This study estimated potential reductions in motor vehicle crashes
      and injuries associated with the use of roundabouts as an alternative to signal
      and stop sign control at intersections in the United States. METHODS: An empiric
      Bayes procedure was used to estimate changes in motor vehicle crashes following
      conversion of 24 intersections from stop sign and traffic signal control to
      modern roundabouts. RESULTS: There were highly significant reductions of 38% for
      all crash severities combined and of 76% for all injury crashes. Reductions in
      the numbers of fatal and incapacitating injury crashes were estimated at about
      90%. CONCLUSIONS: Results are consistent with numerous international studies and
      suggest that roundabout installation should be strongly promoted as an effective
      safety treatment.

PMID- 11291379
TI  - Using aggregate geographic data to proxy individual socioeconomic status: does
      size matter?
AB  - OBJECTIVES: This study assessed whether aggregate-level measures of socioeconomic
      status (SES) are less biased as proxies for individual-level measures if the unit
      of geographic aggregation is small in size and population. METHODS: National
      Health Interview Survey and census data were used to replicate analyses that
      identified the degree to which aggregate proxies of individual SES bias
      interpretations of the effects of SES on health. RESULTS: Ordinary least squares
      regressions on self-perceived health showed that the coefficients for income and
      education measured at the tract and block group levels were larger than those at
      the individual level but smaller than those estimated by Geronimus et al. at the
      zip code level. CONCLUSIONS: Researchers should be cautious about use of proxy
      measurement of individual SES even if proxies are calculated from small
      geographic units.

PMID- 11291380
TI  - Risk of infection from needle reuse at a phlebotomy center.
AB  - OBJECTIVES: This study determined infection risk for HIV, hepatitis B virus
      (HBV), and hepatitis C virus (HCV) from needle reuse at a phlebotomy center that
      possibly exposed 3810 patients to infection. METHODS: We used a model for the
      risk of infection per blood draw, supplemented by subsequent testing results from
      1699 patients. RESULTS: The highest risk of transmission was for HBV infection:
      1.1 x 10(-6) in the best case and 1.2 x 10(-3) in the (unlikely) worst case.
      Subsequent testing yielded prevalence rates of 0.12%, 0.41%, and 0.88% for HIV,
      HBV, and HCV, respectively, lower than National Health and Nutrition Examination
      Survey III prevalence estimates. CONCLUSIONS: The infection risk was very low;
      few, if any, transmissions are likely to have occurred.

PMID- 11291381
TI  - Elective amniocentesis in low-risk pregnancies: decision making in the era of
      information and uncertainty.
AB  - OBJECTIVES: Rational choice theory was applied to explain women's use of
      amniocentesis. Variables included knowledge about prenatal diagnostics,
      attitudes, and emotional preferences. METHODS: Using structured instruments at 9
      to 14 and at 29 to 34 weeks' gestation, we interviewed 232 Israeli women who had
      low-risk pregnancies. RESULTS: Women who had elective amniocentesis (n = 39) were
      more knowledgeable about prenatal diagnostics, risks of invasive procedures, and
      probability of fetal abnormality in high maternal age; had fewer children; and
      had less favorable attitudes toward parenthood than those who had medically
      indicated amniocentesis (n = 57) and those who did not have amniocentesis (n =
      136). CONCLUSIONS: The use and possible overuse of amniocentesis were associated
      with having more information about prenatal diagnostics and definite emotional
      preferences.

PMID- 11291382
TI  - Maturational timing and overweight prevalence in US adolescent girls.
AB  - OBJECTIVES: This study examined the relation of age at menarche to overweight in
      US adolescent girls. METHODS: Effects of age at menarche and race/ethnicity on
      overweight were estimated via logistic regression, after adjustment for
      sociodemographic characteristics, in a sample of 6507 Hispanic, Black, White, and
      Asian American girls who participated in wave 2 of the National Longitudinal
      Study of Adolescent Health. RESULTS: Overweight prevalence rates were
      significantly higher in early maturing adolescents of all racial/ethnic groups
      but highest (57.5%) among early maturing Black girls. Early maturation nearly
      doubled the odds of being overweight (body mass index at or above the 85th
      percentile). CONCLUSIONS: Greater public health attention should be focused on
      the high prevalence of overweight, particularly among minority female
      adolescents.

PMID- 11291383
TI  - Processes for obtaining nonmedical exemptions to state immunization laws.
AB  - OBJECTIVES: This study sought to determine the specific processes required for
      obtaining religious and philosophical exemptions to school immunization laws.
      METHODS: State health department immunization program managers in the 48 states
      that offer nonmedical exemptions were surveyed. Categories were assigned to
      reflect the complexity of the procedure within a state for obtaining an
      exemption. RESULTS: Sixteen of the states delegated sole authority for processing
      exemptions to school officials. Nine states had written policies informing
      parents who seek an exemption of the risks of not immunizing. The complexity of
      the exemption process, in terms of paperwork or effort required, was inversely
      associated with the proportion of exemptions field. CONCLUSIONS: In many states,
      the process of claiming a nonmedical exemption requires less effort than
      fulfilling immunization requirements.

PMID- 11291384
TI  - HIV infection in parents of youths with behaviorally acquired HIV.

PMID- 11291385
TI  - Sexual behavior and condom use among patients with sexually transmitted diseases
      in Jinan, China.

PMID- 11291386
TI  - Emergency department screening for domestic violence.

PMID- 11291387
TI  - Further thoughts on burden of disease methods in Pakistan.

PMID- 11291388
TI  - ProC global: an automated screening test for factor V Leiden and prothrombin
      mutation 20210 G to A detection.

PMID- 11291389
TI  - Managing conflicts at the end of life.

PMID- 11291390
TI  - Depression with psychomotor retardation: diagnostic challenges and the use of
      psychostimulants.
AB  - A patient with advanced pancreatic cancer is presented to demonstrate the
      clinical challenge of diagnosing depression in palliative care. The conundrum
      related to the relative roles of somatic and psychological symptoms in screening
      or diagnosing depression in these patients is illustrated and discussed. There is
      no clear consensus on how to apply diagnostic criteria for diagnosing depression
      in these patients. Although an approach that focuses on the psychological
      symptoms is often suggested, it appears that somatic criteria cannot be entirely
      excluded. The case also highlights the use of methylphenidate to treat palliative
      care patients. As compared to traditional antidepressants that may take as long
      as 6-8 weeks to have a full effect, they offer the advantage of onset of action
      within a few days. This is especially helpful in patients with limited life
      expectancies. They appear to be particularly advantageous where psychomotor
      retardation is a main feature of the depression. The patient discussed
      demonstrated an observed and self-reported improvement of mood and psychomotor
      retardation following the initiation of psychostimulant treatment. Larger,
      controlled trials, using specified criteria to diagnose depression, are warranted
      to elucidate the role of psychostimulants in treating depression in palliative
      care patients.

PMID- 11291391
TI  - Deliberative decision making and the treatment of pain.
AB  - In recent years, increased emphasis has been placed on the ethical duty of
      physicians to relieve pain and suffering. According to a 1992 report from The
      Agency for Health Care Policy Research (AHCPR), the "ethical obligation to manage
      pain and relieve the patient's suffering is at the core of a health care
      professional's commitment." However, despite the increased emphasis on the
      ethical duty to relieve pain, the undertreatment of pain continues to be a
      serious problem. This problem has been widely discussed, but so far efforts to
      respond to it have focused almost exclusively on institutional and educational
      solutions. Yet surprisingly in this discussion very little attention has been
      paid to articulating a constructive role for the patient in combating this
      problem. In this article I argue that adequate pain treatment will often require
      the active participation of the patient in the decision making process. Given the
      special nature of pain and the special problems that arise in the treatment of
      pain, adequate pain treatment requires that physicians and patients realize a
      particular model of shared decision making--one that I refer to as deliberative
      decision making. As will become clear, my defense of this model is limited to the
      context of pain management and may not apply in other clinical contexts.

PMID- 11291392
TI  - Integrating the "new" with the "traditional": an innovative education model.
AB  - In 1998 the Faculty of Pharmacy and Pharmaceutical Sciences at the University of
      Alberta, Canada, introduced a new elective semester course entitled "The Pain
      Module" for pharmacy students in their final year of undergraduate training. The
      aim was to build on the existing theoretical content related to areas such as
      pharmacology and therapeutics and to generate opportunities for skill and
      attitude development, including those related to the management of cancer-related
      pain. Traditional formats such as classroom-based seminars were integrated with
      innovative methods such as computer-mediated discussions and conferencing (CMC)
      and academic bus rounds. The CMC component of the course served to provide
      continuity of discussion between weekly classroom discussions, gave students
      access to content experts on an ongoing basis and furthered learning initiated in
      the classroom. Students were given the opportunity to meet palliative care
      patients being cared for at home and in hospices. A total of 21 students
      participated in all the course activities. By the end of the course, there
      appeared to be a greater appreciation for end-of-life care issues. This
      highlights the need to incorporate end-of-life care into the undergraduate
      curriculum of disciplines other than medicine and nursing. Evaluation of the
      course identified several benefits and limitations of CMC. There was increased
      access to content experts and increased interaction between students. Limitations
      of CMC included increased time commitments and an open-ended nature that was
      uncomfortable for some learners. Other benefits and limitations are described
      further in this article. Future attempts at integrating new instructional
      technologies should be systematically evaluated.

PMID- 11291393
TI  - Experience with neonatal palliative care consultation at the Medical College of
      Wisconsin-Children's Hospital of Wisconsin.
AB  - At Children's Hospital of Wisconsin there is a pediatric palliative care
      consultation service that serves a diverse patient population, including infants.
      However, the value of a palliative care consultation for infants has not been
      well evaluated. We performed a retrospective, case series, descriptive chart
      review of infants in our neonatal intensive care unit (NICU) who received
      palliative care consults between January 1996 and June 1998. We specifically
      looked at their diagnoses, the timing of consults, reasons that consultations
      were ordered, what recommendations were made, and the subsequent outcomes. During
      the series period there were 898 admissions to the NICU, 51 neonatal deaths, and
      12 neonatal palliative care consultations. The diagnostic categories for those
      with a palliative care referral included prematurity, lethal anomalies, and
      catastrophic or overwhelming illness. Reasons for the consultations were
      organization of home hospice, facilitation of medical options, such as do-not
      resuscitate (DNR) orders and treatment withdrawal, facilitation of comfort
      measures, and grief/loss issues. Recommendations that the palliative care staff
      made fell into four categories: advance directive planning, the optimal
      environment for supporting neonatal death, comfort and medical care, and
      psychosocial support. This series is a description of what a palliative care
      service can offer for terminally ill infants in an NICU. We speculate that such
      consults can more consistently and comprehensively provide appropriate end-of
      life care for these patients and their families.

PMID- 11291394
TI  - The palliative medicine extended standardized patient scenario: a preliminary
      report.
AB  - An extended standardized patient scenario (ESPS) is described that utilizes
      standardized patients (SPs) in palliative care education of medical students and
      residents. The goals of the ESPS will be to: (1) improve physician communications
      skills in regard to breaking bad news and end-of-life care; (2) integrate
      evidence-based medicine into patient recommendations; and (3) enhance clinical
      skills in the practice of palliative medicine, particularly the evaluation and
      management of total suffering. The main features of the ESPS include a single SP
      scenario that is presented over several sessions, portraying an extended period
      in the patient's life. The ESPS requires little in the way of equipment, but is
      labor intensive. The ESPS is a promising modality that deserves further scrutiny
      and outcomes research.

PMID- 11291395
TI  - The International Association for Hospice and Palliative Care (IAHPC): history,
      description, and future direction.

PMID- 11291396
TI  - Letting people go.

PMID- 11291397
TI  - Hospice volunteer training for health science students: an academic medical
      center-hospice community partnership.
AB  - Within the academic medical center providing interdisciplinary, experiential,
      longitudinal, and mentored learning experiences for students regarding
      hospice/end-of-life care is a considerable challenge. This article describes an
      innovative course for medical, nursing, and social work students taught as a
      partnership among the departments of family medicine, medical history/ethics and
      three community hospice programs. The goals of the course are: (1) understanding
      the hospice philosophy of care; (2) understanding that hospice care is an
      interdisciplinary team process; and (3) development of the caregiver skills of
      self-reflection as a form of self-knowledge while participating in the care of
      terminally ill patients. Achieving these goals is challenging for students
      (especially medical students) and faculty but highly rewarding. The development,
      implementation and evolution over the past 3 years of this hospice volunteer
      training course are discussed.

PMID- 11291398
TI  - The challenge of chronic AIDS-related nausea and vomiting.

PMID- 11291399
TI  - A national strategy for palliative care in New Zealand.
AB  - Despite the evidence that palliative care is effective in improving the quality
      of life for people who are dying, it is still poorly understood by many health
      professionals in New Zealand. Many in the general public still see the focus of
      hospice care as dying rather than living. In 1998, the New Zealand National
      Advisory Committee on Health and Disability (National Health Committee)
      established a Working Party on the "Care of People Who Are Dying." This was in
      response to the failure of other earlier processes to produce any lasting,
      noticeable change in the provision of or access to palliative care services.
      During 1999/2000 an advisory group, comprising members with differing areas of
      expertise in palliative care, drew on that previous work and with the Ministry of
      Health, Health Funding Authority, and National Health Committee produced a
      report, The New Zealand Palliative Care Strategy. This article summarizes the
      recommendations of the report, and describes the professional-governmental
      collaboration that led to its publication.

PMID- 11291400
TI  - Differing perceptions of end-of-life care in long-term care.
AB  - BACKGROUND: Care team members may have different views on end-of-life care, which
      may influence perceptions of that care. METHODS: Twenty-seven consecutive deaths
      at a long-term care facility were identified. A structured interview of primary
      care team members (physician, nurse, and aide) was administered. The interview
      asked comparable questions to each group on a Likert scale (1 = least satisfied;
      4 = most satisfied) regarding the resident's experience in the last 3 days of
      life. Areas assessed were pain, comfort, emotional support, adequacy of
      information provided to families, whether direct care needs were met, supportive
      care, time spent with resident, number of symptoms present at the end of life,
      and quality of death. Repeated measures analysis of variance was used to
      determine if the mean values of various response measures differed significantly
      by rater group (i.e., physicians, nurses, or aides). RESULTS: Aides perceived
      more resident pain compared to physicians or nurses. Physicians' perceptions of
      emotional support provided to families were lower than those of aides or nurses.
      CONCLUSIONS: This study demonstrates differing perceptions by care team members
      regarding end-of-life care. Areas of difference include pain and emotional
      support provided to families. Because effective team functioning requires
      understanding and recognition of different perceptions of team members,
      clarifying and addressing the reasons for these differences may improve both job
      satisfaction on the part of care team members, as well as the quality of end-of
      life care delivered.

PMID- 11291401
TI  - Litigating around ERISA to quality managed healthcare: an HMO can breach
      fiduciary duties.

PMID- 11291403
TI  - Human genome: how much do we know?

PMID- 11291402
TI  - Pyogenic liver abscesses due to Klebsiella pneumoniae in a diabetic patient.
AB  - Pyogenic liver abscess due to Klebsiella pneumoniae is a rare clinical entity. It
      has emerged as an important infection complication in diabetics and its incidence
      in diabetics without intraabdominal or biliary tract infections is increasing. We
      present herein a case of multiple pyogenic liver abscesses due to K. pneumoniae
      in a diabetic patient and discuss clinical course, treatment and possible reasons
      for association between K. pneumoniae liver abscess and diabetes.

PMID- 11291404
TI  - Obstetric ultrasound--the facts.

PMID- 11291405
TI  - CPD--a valuable initiative.

PMID- 11291406
TI  - Hyperbaric oxygen therapy in cerebral palsy.

PMID- 11291407
TI  - Palliation of recurrent carcinoma of the cervix in a district hospital.

PMID- 11291408
TI  - Is recall age of menarche reliable?

PMID- 11291409
TI  - First S.A. living liver donors?

PMID- 11291410
TI  - Ultrasound dealer infuriates.

PMID- 11291411
TI  - Partnering life....

PMID- 11291412
TI  - Mpuntsha urges adapt or wither.

PMID- 11291413
TI  - Fickle consumers warn industry.

PMID- 11291414
TI  - Host and viral factors that impact on HIV-1 transmission and disease progression
      in South Africa.

PMID- 11291415
TI  - The Aversion Project--psychiatric abuses in the South African Defence Force
      during the apartheid era.

PMID- 11291416
TI  - The hepatic bruit.

PMID- 11291417
TI  - Near-fatal asphyxiation in sawdust--an unusual tracheobronchial foreign body.

PMID- 11291418
TI  - MCC resolves on phenylpropanolamine (PPA) safety.

PMID- 11291419
TI  - World Health Day 2001--'mental health'.

PMID- 11291420
TI  - Fetal nuchal translucency scan--its correct place in fetal evaluation.

PMID- 11291421
TI  - Frequent detection of high viraemia in HBeAg-negative South African carriers.

PMID- 11291423
TI  - Allergenicity and cross-reactivity of buffalo grass (Stenotaphrum secundatum).
AB  - BACKGROUND: In the subtropical climate of South Africa, grasses of the subfamily
      Panicoideae are predominant. Bermuda grass has previously been shown to be an
      important local allergen, and immunoglobulin E (IgE) epitopes of Bermuda grass
      extracts are known to be distinct from those of the Pooid pollen extracts.
      Following our demonstration of sensitivity in 43% of patients grass-allergic to
      the Panicoid, Kikuyu grass, we have studied the closely related buffalo grass,
      Stenotaphrum secundatum, indigenous to the Western Cape region, the east coast of
      Africa and the oceanic islands such as Mauritius; and Eragrostis, another common
      indigenous grass with a wide distribution. OBJECTIVE: To partially characterise
      the allergens of buffalo pollen, and examine its immunological relationships with
      local common grasses such as Eragrostis and Kikuyu. METHODS: Grass-allergic
      patients were evaluated clinically, and skin prick tests (SPTs) and radio
      allergosorbent tests (RASTs) to Bermuda and grass mix were performed. Sera of
      timothy grass-sensitive patients from Belgium were also included in this study.
      Pollen extract from buffalo grass was characterised by specific IgE binding by
      means of immunoblotting and enzyme-linked immunosorbent assay (ELISA). Cross
      reactivity between the grasses was studied by means of inhibition of IgE binding.
      RESULTS: More than 90% of grass-sensitive patients were found to have IgE
      antibodies to Buffalo and Eragrostis pollen. Inhibition of ELISA and immunoblots
      revealed that extracts of these grass pollens could significant inhibit IgE
      binding to the local grass pollens, Kikuyu, buffalo, Eragrostis and Bermuda on
      solid phase, but 100% inhibition was never achieved, indicating that cross
      reactive but also unique epitopes are present. We also identified a subset of
      patients with negative RASTs to Bermuda, and minimal inhibition by Bermuda pollen
      extract. CONCLUSION: Buffalo and Eragrostis are important aeroallergens in the
      Cape, dispersed during the long dry, windy summer. Our data suggest that the
      local grasses are major sensitisers, and that South African diagnostic panels
      should include extracts of buffalo and Eragrostis grasses.

PMID- 11291422
TI  - Effect of the whistle watch device on bronchodilator use in children with asthma.
AB  - OBJECTIVE: To determine if the use of the whistle watch (WW), a simple device to
      monitor peak flow rate, affects the use of bronchodilators at home. STUDY DESIGN:
      Prospective, randomised, crossover design. SETTING: The asthma outpatients'
      clinic at Coronation Hospital, a tertiary care centre in Johannesburg. PATIENTS
      AND METHODS: Children between 6 and 18 years of age with moderate or severe
      asthma for more than a year were enrolled. They were randomised into two groups,
      with bronchodilator use determined either by the WW or solely by the patient's
      perceived symptomatology. The patients acted as their own controls, switching
      over to the other group after 30 days. Eighty patients were enrolled into the
      study. RESULTS: Forty-three patients completed the study (54%). There were no
      significant differences between these patients and those who did not complete the
      study in terms of sex, age and treatment characteristics. There was a significant
      reduction in the mean monthly number of bronchodilator doses used by the WW group
      (5.5 doses v. 16.81 doses, paired t-test, t = 3.64, P < 0.001, 95% confidence
      interval (CI) 6.1-16.55). The change in individual participants varied between 13
      extra bronchodilator doses and 71 fewer doses per month with the use of the WW
      device. CONCLUSION: The WW device is a cheap, easy-to-use and effective tool that
      reduces the number of bronchodilator doses used by asthmatic children at home.

PMID- 11291424
TI  - Urbanisation and adolescent risk behaviour.
AB  - OBJECTIVE: To investigate whether there is an association between the length of
      time lived in an urban area and selected adolescent risk behaviours. DESIGN:
      Cross-sectional survey in which students completed an anonymous, confidential
      questionnaire. SETTING: Four high schools in black communities in the Cape
      Peninsula, South Africa. PARTICIPANTS: A sample of 1,296 students obtained by
      multistage cluster sampling. MAIN OUTCOME MEASURES: Selected risk behaviours.
      RESULTS: There is a relationship between urbanisation and certain risk
      behaviours. The following risk behaviours were associated with urbanisation: use
      in the previous month of alcohol, cannabis, and cannabis mixed with Mandrax;
      being a victim of violence; perpetration of an act of violence; and suicidality.
      Conversely, participation in sexual intercourse and solvent sniffing in the
      previous month were not associated with urbanisation. CONCLUSION: Urbanisation is
      associated with an increase in the prevalence rates of some risk behaviours.
      Mental health promotion efforts may be informed by further research aimed at the
      identification of: (i) the characteristics of risk behaviour that determine
      whether it is associated with urbanisation; and (ii) where applicable, the
      specific aspects of the urbanisation process that contribute to an increase in
      risk.

PMID- 11291425
TI  - Global health strategies versus local primary health care priorities--a case
      study of national immunisation days in Southern Africa.
AB  - Building on the successful eradication of smallpox, the World Health
      Organisation, together with other agencies, is now moving quickly to the
      eradication of poliomyelitis, originally aimed for the year 2000. Plans for the
      subsequent global eradication of measles are in an advanced stage. Eradication of
      both polio and measles incorporate as a fundamental strategy high routine
      coverage, surveillance and special national immunisation days (NIDs), which are
      supplementary to routine vaccination services. There has been a lively debate on
      whether poor countries, with many health problems that could be controlled,
      should divert their limited resources for a global goal of eradication that may
      have low priority for their children. From a cost-effectiveness perspective, NIDs
      are fully justifiable. However, field observations in sub-saharan Africa show
      that NIDs divert resources and, to a certain extent, attention from the
      development of comprehensive primary health care (PHC). The routine immunisation
      coverage rates dropped on average since the introduction of NIDs in 1996, which
      is contrary to what was observed in the western Pacific and other regions. The
      additional investment to be made when moving from disease control to eradication
      may exceed the financial capacity of an individual country. Since the
      industrialised countries benefit most from eradication, they should take
      responsibility for covering the needs of those countries that cannot afford the
      investment. The WHO's frequent argument that NIDs are promotive to PHC is not
      confirmed in the southern African region. The authors think that the WHO should,
      therefore, focus its attention on diminishing the negative side-effects of NIDs
      and on getting the positive side-effects incorporated in the integrated health
      services in a sustainable way.

PMID- 11291426
TI  - Contribution of growth hormone-releasing hormone and somatostatin to decreased
      growth hormone secretion in elderly men.
AB  - OBJECTIVE: The pathophysiology of the decline in circulating growth hormone (GH)
      concentrations that may occur with ageing remains elusive. We have investigated
      the potential contributions of decreased endogenous GH-releasing hormone (GHRH)
      and increased somatostatin secretion to this phenomenon. DESIGN AND METHODS: The
      strategy used was to stimulate GH secretion in 8 young (20-24 years old, body
      mass index (BMI) 22.8 +/- 2.8 kg/m2) and 8 elderly (68-82 years old, BMI 23.4 +/-
      1.6 kg/m2) male subjects on separate occasions by means of: (i) intravenous bolus
      0.5 microgram/kg D-Ala2 GHRH(1-29)-NH2 alone; (ii) 0.5 microgram/kg GHRH after
      pre-treatment with two oral doses of 50 mg atenolol (to inhibit somatostatin
      secretion); (iii) 1.25 mg oral bromocriptine alone (to increase endogenous GHRH
      and/or inhibit somatostatin); (iv) 50 mg oral atenolol plus 1.25 mg oral
      bromocriptine; and (v) 0.5 microgram/kg GHRH after pre-treatment with 1.25 mg
      oral bromocriptine. RESULTS: The elderly men had a significantly lower peak and
      area under curve (AUC) GH response to intravenous GHRH when compared with 8 young
      men (peak 3.1 +/- 1.0 ng/ml v. 21.6 +/- 5.0 ng/ml, AUC 205 +/- 56 ng/ml/min v.
      1,315 +/- 295 ng/ml/min, P < 0.05). Pre-treatment with atenolol before GHRH
      administration produced no significant increase in peak and AUC GH response in
      both groups, which remained lower in the elderly men than in their young
      counterparts (peak 5.5 +/- 1.8 ng/ml v. 29.3 +/- 7.0 ng/ml, AUC 327 +/- 90
      ng/ml/min v. 2,017 +/- 590 ng/ml/min, P < 0.05). Bromocriptine alone did not
      cause a significant rise in GH concentration in either elderly or young subjects
      (peak 3.1 +/- 1.1 v. 8.8 +/- 3.2 ng/ml, P > 0.05). When atenolol was administered
      before bromocriptine, both groups responded but the elderly subjects had a
      significantly greater peak and AUC response (peak 3.6 +/- 0.7 v. 10.7 +/- 2.1
      ng/ml; AUC 191 +/- 39 v. 533 +/- 125 ng/ml/min, P < 0.05). Bromocriptine given
      before GHRH failed to potentiate GHRH action on GH release in either group. Of 5
      elderly men who underwent further evaluation of GH secretory ability, 2 subjects
      had GH levels > 10 ng/ml, either basally or after intravenous GHRH. The remaining
      3 had an initially impaired GH response to bolus intravenous GHRH. After 100
      micrograms GHRH subcutaneously twice daily for up to 2 weeks the GH responses to
      intravenous bolus GHRH (0.5 microgram/kg) were reassessed. One exhibited a normal
      response (> 10 ng/ml) after 1 week of daily GHRH treatment, another had a near
      normal response after 2 weeks (9.7 ng/ml), while the third still had an impaired
      response by the end of the 2-week treatment period (3.2 ng/ml). CONCLUSIONS: The
      restoration of endogenous GH secretion in these elderly subjects by means of GHRH
      priming, and the failure of manipulation of somatostatinergic tone to restore a
      normal GH response to GHRH suggests that somatotroph atrophy due to a reduction
      in endogenous GHRH secretion is the principal cause of the diminished GH
      secretion with ageing.

PMID- 11291427
TI  - Profound inhibition of GPIb, GPIIb/IIIa, PECAM-1, CD63, and CD107 in a chronic
      drug addict: selecting controls for platelet flow cytometry in the inner city
      hospital.

PMID- 11291428
TI  - Resuming research after having a stroke.

PMID- 11291429
TI  - Sexual abuse and sexual risk behaviors of minority women with sexually
      transmitted diseases.
AB  - The relationship between sexual abuse and sexually transmitted disease (STD)
      represents an important and underinvestigated context of domestic violence. This
      study examined the association between sexual abuse, sexual risk behaviors, and
      risk for reinfection and HIV among minority women with STD. Mexican American and
      African American women (n = 617) with active STD entered a randomized study of
      behavioral intervention to reduce STD recurrence. Each underwent questioning at
      entry regarding sexual abuse and sexual risk behaviors. Comparisons of these
      behaviors using chi-square, t tests, and logistic regression were made by history
      of sexual abuse. Sexually abused women were more likely to have lower incomes,
      earlier coitus, STD history, currently abusive partners, new sex partners, anal
      sex, and bleeding with sex, placing them at increased risk for STD reinfection
      and HIV. Due to this association with sexual risk behavior, assessment for sexual
      abuse is essential in programs focusing on STD/HIV prevention.

PMID- 11291430
TI  - Chinese students' concept of mental health.
AB  - This study explored Chinese students' concept of mental health through a
      questionnaire completed by 999 students from six primary schools, six high
      schools, and three universities in Shanghai. The results confirmed the
      expectation that Chinese students' mental health concept would be multifaceted
      and would reflect psychological, physical, and sociocultural factors. An
      exploratory factor analysis on 12 mental health items with a subsample extracted
      a three-factor model, which was cross-validated by confirmatory factor analysis
      with a different subsample. These three factors were labeled as Affective
      Strength, Adaptive Strength, and Personal Strength. No gender differences were
      found. The grade differences supported the notion that Chinese students' concept
      of mental health seems to be more consistent with the developmental paradigm of
      health. The senior years in primary school could be the turning point at which
      children start to conceptualize health as a holistic experience by recognizing
      the importance of mental health.

PMID- 11291431
TI  - Cardiovascular disease risk factors in Korean American elderly.
AB  - An in-depth cardiovascular risk factor assessment was carried out in a sample of
      205 Korean American elderly in Maryland, consisting of 75 males and 130 females
      aged 60 to 89 years (mean age = 69.9 +/- 6.5 years). Six risk factors were
      assessed in each participant: high blood pressure, current smoking, high blood
      cholesterol, overweight, sedentary lifestyle, and diabetes. The findings of this
      cross-sectional study suggested that high blood pressure was the leading
      cardiovascular disease risk factor among Korean American elderly (71%), followed
      by high blood cholesterol (53%), overweight (43%), sedentary life style (24%),
      diabetes (18%), and smoking (7%). Two thirds of the sample had multiple
      cardiovascular disease risk factors. The pattern of prevalence and risk factors
      that was observed was consistent with the distribution of multiple risk factors
      in that the combination of high blood pressure, high blood cholesterol, and
      overweight was most common in Korean American elderly (62%). These findings
      indicate that culturally relevant and salient strategies are needed to reduce
      multiple risk factors in this population.

PMID- 11291432
TI  - Impact of cognitive impairment on wandering behavior.
AB  - The purpose of this study was to explore cognitive impairment as a predictor of
      wandering rhythm and pattern in a sample of 25 demented residents from two long
      term care settings. Parameters of rhythm indicating cycle frequency and structure
      were examined for wandering patterns (random, lapping, and pacing) and for
      nonwandering (direct) ambulation. All measures of cognitive impairment (Mini
      Mental State Exam, Mattis Dementia Rating Scale, and a neuropsychologist's
      clinical rating) were significant predictors of parameters signifying frequency
      of wandering for random and lapping patterns but not for the pacing pattern. In
      addition, for nonwandering ambulation, cognitive impairment predicted some
      parameters of cycle structure (mean locomoting and nonlocomoting phase durations)
      but not those denoting frequency of ambulation. Results indicate that cognitive
      impairment plays an important role in determining the frequency of wandering
      cycles, but other factors may better explain parameters that characterize its
      cycle structure.

PMID- 11291433
TI  - A descriptive study of function in acute motor stroke.
AB  - The functional independence measure (FIM) instrument was introduced in 1987 and
      has proven to be a useful tool for measuring disability in different patient
      populations. The FIM instrument data collected during inpatient rehabilitation
      for stroke is very informative, as it is voluminous, comprehensive, and has a
      uniform reporting mechanism. In contrast to inpatient rehabilitation, there is a
      paucity of FIM instrument data on acute stroke patients. The purpose of this
      study was to describe functional level of 100 patients within the first 24 hours
      of acute care admission. The mean total FIM instrument score was 94.05 (SD +/-
      19.31, range = 38-120), the mean motor domain subscore was 61 (SD +/- 17.8, range
      23-85), and cognitive was 33.4 (SD +/- 3.3, range 15-35). Significant group
      differences were identified for age, gender, and disposition for total and/or
      domain subscores. Significant differences in age, gender, employment, and
      disposition were found for clinical subscales. This study fills a gap in current
      knowledge, that of baseline total FIM instrument scores, domain subscores, and
      six clinical subscales on one particular group of stroke patients, those with a
      primary motor stroke.

PMID- 11291434
TI  - Measuring nurses' self-concept.
AB  - Little is known of nurses' self-concept in light of their professional identity
      or as working adults. This article explores the development and rigorous testing
      of a new self-concept instrument designed specifically for nurses. The new
      measure is based on the self-concept measurement theory of Shavelson, Hubner, and
      Stanton. An expert panel was used to critique and aid refinement of the measure.
      The dimensions of nurses' self-concept were measured in six scales: General
      Nursing, Care, Staff Relations, Communication, Knowledge, and Leadership. Two
      groups participated in this study: Group 1 consisted of nursing students prior to
      graduation (n = 506) and Group 2 consisted of randomly selected, experienced,
      working nurses (n = 528). A series of exploratory and confirmatory factor
      analyses were conducted to test the fit of a priori models. The results indicate
      that all scales possess good construct validity and a satisfactory fit with the
      data.

PMID- 11291435
TI  - Perchlorate levels in samples of sodium nitrate fertilizer derived from Chilean
      caliche.
AB  - Paleogeochemical deposits in northern Chile are a rich source of naturally
      occurring sodium nitrate (Chile saltpeter). These ores are mined to isolate NaNO3
      (16-0-0) for use as fertilizer. Coincidentally, these very same deposits are a
      natural source of perchlorate anion (ClO4-). At sufficiently high concentrations,
      perchlorate interferes with iodide uptake in the thyroid gland and has been used
      medicinally for this purpose. In 1997, perchlorate contamination was discovered
      in a number of US water supplies, including Lake Mead and the Colorado River.
      Subsequently, the Environmental Protection Agency added this species to the
      Contaminant Candidate List for drinking water and will begin assessing occurrence
      via the Unregulated Contaminants Monitoring Rule in 2001. Effective risk
      assessment requires characterizing possible sources, including fertilizer.
      Samples were analyzed by ion chromatography and confirmed by complexation
      electrospray ionization mass spectrometry. Within a lot, distribution of
      perchlorate is nearly homogeneous, presumably due to the manufacturing process.
      Two different lots we analyzed differed by 15%, containing an average of either
      1.5 or 1.8 mg g-1. Inadequate sample size can lead to incorrect estimations; 100
      g samples gave sufficiently consistent and reproducible results. At present,
      information on natural attenuation, plant uptake, use/application, and dilution
      is too limited to evaluate the significance of these findings, and further
      research is needed in these areas.

PMID- 11291436
TI  - Use of passive ambient ozone (O3) samplers in vegetation effects assessment.
AB  - A stochastistic, Weibull probability model was developed and verified to simulate
      the underlying frequency distributions of hourly ozone (O3) concentrations
      (exposure dynamics) using the single, weekly mean values obtained from a passive
      (sodium nitrite absorbent) sampler. The simulation was based on the data derived
      from a co-located continuous monitor. Although at the moment the model output may
      be considered as being specific to the elevation and location of the study site,
      the results were extremely good. This effort for the approximation of the O3
      exposure dynamics can be extended to other sites with similar data sets and in
      developing a generalized understanding of the stochastic O3 exposure-plant
      response relationships, conferring measurable benefits to the future use of
      passive O3 samplers, in the absence of continuous monitoring.

PMID- 11291437
TI  - Chlorinated pesticides and PCBs in sediments and molluscs from freshwater canals
      in the Hanoi region.
AB  - The concentrations of organochlorine pesticides and PCBs were determined in
      surface sediments and freshwater molluscs (Angulyagra sp.) from water canals in
      the region of Hanoi city. Results obtained show that the concentration of sigma
      DDT compounds in sediments range from 7 to 80 ng/g (dry weight) and from 6 to 864
      ng/g (dry weight) in the soft tissues of molluscs. The concentrations of sigma
      DDTs were higher in populated sites and much lower in rural sites, indicating
      that the DDT has been used for mosquito control and not as a crop protection
      chemical. Hexachlocyclohexanes (HCHs) have also been widely used in the region
      but the current environmental concentrations are much lower than those of DDT's,
      which is due to the less persistence of those compounds. Polychlorinated
      biphenyls (PCBs) were measured, for example as aroclor 1254, in concentrations up
      to 40 ng/g (dry weight) and up to 76 ng/g (dry weight) in sediments and molluscs,
      respectively. Molluscs from water canals are a very popular food in the region.
      Taking into consideration the high DDT levels measured in these molluscs their
      consumption is worrisome and may expose the population to high levels of
      endocrine disrupting substances. Current PCB levels in sediments are lower than
      usually measured in industrialized countries. Therefore, PCB concentrations in
      aquatic molluscs are still also relatively low. These snails do not have enzyme
      ability to metabolize most of the CB congeners and, thus, are passive
      accumulators and a significant transfer pathway of CBs to consumers. Therefore,
      measures to phase out the use of these persistent and bioaccumulable chemicals
      should be adopted in order to prevent further environmental contamination.

PMID- 11291438
TI  - Effects of alkaline dust deposits from phosphate fertilizer production on
      microbial biomass and enzyme activities in grassland soils.
AB  - Microbial biomass carbon (Cmic) and soil enzyme activities were measured at 12
      sites along a gradient of former emissions of phosphate fertilizer production.
      Seven years after close down of operation, still moderate to high total
      concentrations of the dust constituents cadmium (up to 33 mg kg-1 dw), fluoride
      (5300 mg kg-1 dw) and phosphorous (120,000 mg kg-1 dw) were found in topsoils of
      contaminated sites. Accumulation of partially decomposed plant matter, soil
      respiration and dehydrogenase activity paralleled the increase of dust deposits,
      whereas microbial biomass decreased along the gradient. A significant negative
      correlation was obtained between the Cmic-to-Corg-ratio and the concentration of
      contaminants. In contrast, the Cmic-specific respiration (qCO2) and the
      dehydrogenase activity-to-Cmic-ratio were positively correlated. The low Cmic
      values and the enhanced activities in the contaminated soils are suggested as a
      response of microbial communities to environmental stress or ecosystem
      disturbances. The apparently missing detrimental effects of the alkaline deposits
      on soil microbial activities are probably due to the low bioavailability of
      contaminants in the calcareous soil.

PMID- 11291439
TI  - Influence of organic amendments on copper distribution among particle-size and
      density fractions in Champagne vineyard soils.
AB  - The intensive use for over 100 years of copper sulfate (Bordeaux mixture) to
      fight against mildew in vineyard soils has led to an important, widespread
      accumulation of Cu (100 to 1500 mg Cu kg-1 soil). In Champagne vineyards, organic
      amendments are used currently to increase soil fertility and to limit soil
      erosion. Organic amendments may have a direct effect on the retention of Cu in
      the soil. To assess the influence of the organic management on the fate of Cu in
      calcareous Champagne vineyard soils, we studied Cu distribution (1) in the soil
      profile and (2) among primary soil particles, in vineyard parcels with different
      amendments. Amendments were oak-bark, vine-shoots and urban compost. The results
      were compared with the amount and the distribution of Cu in an unamended
      calcareous soil. Physical soil fractionations were carried out to separate soil
      primary particles according to their size and density. Cu has a heterogeneous
      distribution among soil particle fractions. Two fractions were mainly responsible
      for Cu retention in soils: the organic debris larger than 50 microns or coarse
      particulate organic matter (POM) issued from the organic amendments, and the clay
      sized fraction < 2 microns. The POM contained up to 2000 mg Cu kg-1 fraction and
      the clay fraction contained up to 500 mg Cu kg-1 fraction. The clay-sized
      fraction was responsible for almost 40% of the total amount of Cu in the four
      parcels. POM was predominantly responsible for the differences in Cu contents
      between the unamended and the three amended parcels. Our results attested that
      methods of soil particle-size fractionation can be successfully used to assess
      the distribution of metal elements in soils.

PMID- 11291440
TI  - Understorey vegetation along a heavy-metal pollution gradient in SW Finland.
AB  - Understorey vegetation of Scots pine forests was studied along a 8-km transect
      running SE from a Cu-Ni smelter at Harjavalta, SW Finland. Long-term accumulation
      of heavy metals and sulphur in the forest ecosystem has drastically changed plant
      communities. Vegetation was almost absent up to a distance of 0.5 km from the
      smelter. The total coverage and the number of plant species increased with
      increasing distance from the smelter. Ordination by global non-metric
      multidimensional scaling (GNMDS) indicated that the floristic composition was
      differentiated in response to the pollution level. The main compositional
      gradient of GNMDS was correlated with the heavy metal concentrations in the
      organic soil layer and with the size of the overstorey trees. Vascular plants
      were more pollution-resistant than ground lichens, whereas mosses were the most
      sensitive plant group. In addition to heavy metals, nutrient imbalances and the
      considerably reduced water-holding capacity of the surface soil also restrict
      plant recolonisation on the degraded sites.

PMID- 11291441
TI  - New methods of nitrate removal from water.
AB  - Nitrate contamination in groundwater resources originates mainly from the
      excessive use of fertilisers and uncontrolled land discharges of treated
      wastewater. This can cause potential health hazards to infants and pregnant
      women, thus limiting the direct use of the groundwater resources for the human
      consumption in several parts of the world, including India. The conventional
      processes used to eliminate nitrate from water are ion exchange, reverse osmosis
      and electro-dialysis. The utility of these processes has been limited due to
      their expensive operation and subsequent disposal problem of the generated
      nitrate waste brine. This paper presents a comprehensive account of the
      methods/techniques used for the removal of nitrate ion from water during the last
      10 years with special reference to the biological denitrification and fate of the
      metals in decontamination processes.

PMID- 11291442
TI  - 230Th/232Th activity ratios as a chronological marker complementing 210Pb dating
      in an estuarine system affected by industrial releases.
AB  - The main purpose of this research is to show the usefulness of the 230Th/232Th
      activity ratios as a chronological marker that can be helpful in the dating of
      sediment cores collected from an estuarine system located in the south west of
      Spain highly polluted by wastes from fertilizer plants. These wastes, being
      released for 30 years, and enriched in radionuclides from the uranium series
      including 210Pb, invalidate the application of the 210Pb dating technique in full
      extent to the sediment cores collected in this estuary. However, the evaluation
      and the interpretation of both 210Pb and 230Th/232Th profiles allows the
      determination of average sedimentation rates in different parts of the cores,
      contaminated and noncontaminated zone, that agree in the case analysed in this
      research. Through this approach, a confident chronology covering the last
      century, which is essential to analyse and reconstruct the historical evolution
      of other pollutants in this heavily contaminated system can be established.

PMID- 11291443
TI  - Spotting zones of dissimilatory sulfate reduction in a forested catchment: the
      34S-35S approach.
AB  - The localization of sulfate reducing sites in forested catchments is of major
      importance, because dissimilatory sulfate reduction can be a considerable sink
      for deposited sulfate. To localize dissimilatory sulfate reduction sites in a
      forested catchment (northeastern Bavaria, Germany), three sites within the
      catchment (upland site, intermittent seep, fen) were investigated for delta 34S
      depth profiles of soil sulfur and potential sulfate reduction rates were measured
      with 35S radiolabeling. Stable sulfur isotopes indicate that aerobic metabolism
      is the dominant process on the upland site and the intermittent seep (delta 34S
      of soil sulfur between +1.6 and +9.0@1000) and dissimilatory reduction is not a
      significant sink for sulfate. However, results of the 35S radiolabeling indicated
      for the upland site that the soil has potentially high sulfate reduction rates
      under laboratory conditions. Soil sulfur of the fen was markedly depleted in 34S
      (delta 34S between -6 and +2.6@1000). Both, 34S and 35S data indicated that
      dissimilatory sulfate reduction is an ongoing process on this site. The 34S and
      35S approaches are complementary. While measurements using 35S can show momentary
      potential for dissimilatory bacterial sulfate reduction, delta 34S data reflect
      long-term predominance of either assimilatory or dissimilatory S metabolism at a
      particular site.

PMID- 11291444
TI  - Environmental toxicity assessment in the Parana river delta (Argentina):
      simultaneous evaluation of selected pollutants and mortality rates of Corbicula
      fluminea (Bivalvia) early juveniles.
AB  - Water and sediment samples were collected in the lower Parana delta at four sites
      with different levels of exposure to pollution to evaluate the anthropogenic
      impact through chemical analyses and mortality bioassays. Individual
      polychlorinated biphenyls, chlorinated pesticides, aliphatic hydrocarbons,
      polycyclic aromatic hydrocarbons, and heavy metals were measured in waters,
      porewaters and sediments. The same three phases were also subjected to toxicity
      assays with straight-hinged juveniles of Corbicula fluminea. Concentrations of
      several pollutants were above levels recommended for the protection of aquatic
      life: in waters, Zn, Cu and Cr were 1.6-4.9 times higher, whereas in the
      sediments Cr was 1.8-3.6, and benzo(a)pyrene was 2.8-5.6 times higher. Pollutant
      concentrations followed a clear geographic pattern with highest values in the
      densely populated area of the Reconquista and Lujan rivers, lower levels in the
      San Antonio, and lowest loadings in the remote Parana de las Palmas. This
      gradient was adequately matched by the pattern of mortality rates of C. fluminea
      early juveniles, which were highest in the Reconquista-Lujan (40-93%) and lowest
      (and not significantly different from the control) in the Parana (3.3-23%).
      Mortality rates also increased from surface waters (3.3-53%), to porewaters (12
      73%), to sediments (23-93%). Although toxicity was probably mainly due to
      dissolved contaminants, agreement between chemical and biological evidence of
      pollution was best for the sediment compartment, whereas porewater and surface
      water showed a higher degree of variability.

PMID- 11291445
TI  - Cytogenetic monitoring of men occupationally exposed to airborne pollutants.
AB  - A study of structural chromosomal aberration frequencies in peripheral blood
      lymphocytes was performed in a group of 20 professional drivers exposed to
      airborne pollutants and 20 matching controls. The subjects in the latter group
      were of the same sex (males) and of similar age as the exposed ones, and also had
      similar habits of smoking and alcohol. A statistically significant increase of
      chromosomal aberration was observed in the exposed subjects over the control
      group. An increasing trend of aberrations was observed with the duration of
      service (exposure) in the exposed individuals. This study clearly indicates the
      effect of occupational exposure to airborne pollutants.

PMID- 11291446
TI  - Speciation of rare earth elements in soil and accumulation by wheat with rare
      earth fertilizer application.
AB  - A greenhouse study was conducted to investigate the accumulation of rare earth
      elements (REEs), La, Ce, Pr and Nd, in winter wheat (Triticum aestivum L.), and
      the speciation of these elements in soil following the application of REE-based
      fertilizers. Improved crop yield was confirmed by the experiment. The
      accumulation behavior of La, Ce, Pr and Nd in wheat varied depending on the
      concentration of REE fertilizer application, i.e. increased with increasing REE
      concentration at low fertilization application, constant over the medium REE
      range, and decreased with increasing REE concentration at high fertilizer
      application. Significant negative correlation was obtained between REE contents
      in roots and soil pH (r = -0.5787 to -0.8442 for La). REEs in both the fertilized
      and unfertilized soils were fractionated by a three-stage sequential extraction
      procedure into three chemically distinct fractions: water soluble, exchangeable
      and carbonate bound (B1), Fe-Mn oxide bound (B2), and organic and sulfide bound
      (B3). REEs in fertilized soils were found mainly in the B2 and B3 fractions, with
      only a small amount in the B1 fraction. REEs in B1 and B2 fractions were
      negatively correlated with soil pH (r = -0.6892 to -0.8927 and -0.7462 to 
      0.9482). Significant correlation was obtained between REEs in B1 fraction and REE
      contents in root. The correlation coefficients ranged from 0.6159 to 0.7410 when
      fertilizer application was lower than 20.0 mg/kg soil. No acceptable relationship
      was observed between REE contents in shoot and any of the extractable fractions
      in soils.

PMID- 11291447
TI  - The accumulation of polycyclic aromatic hydrocarbons in lubricating oil over time
      -a comparison of supercritical fluid and liquid-liquid extraction methods.
AB  - Optimal extraction conditions including extraction temperature, fluid density of
      carbon dioxide and concentration of modifier for supercritical fluid extraction
      (SFE) to extract of 16 2-6-ring polycyclic aromatic hydrocarbons (PAHs) spiked
      into used lubricating oil collected from a gasoline-driven automobile were
      determined. A comparison of extraction efficiency 2-6-ring PAHs spiked into the
      used lubricating oil extracted by SFE and liquid-liquid extraction (LLE) methods
      was made. Results indicated that recoveries of PAHs extracted by SFE from the
      used lubricating oil were higher than those by LLE. PAH profiles of lubricating
      oil samples collected at various driving distances from an old and a new gasoline
      driven automobiles were determined by combining SFE, gel permeation
      chromatography clean up and gas chromatography-mass spectrometry analysis.
      Results showed that the concentrations of total PAH in lubricating oils collected
      from both automobiles increased rapidly after oil change. Two- and three-ring
      PAHs dominated the PAH profiles of oil samples collected from both automobiles.
      High concentrations of the more toxic 4-6-ring PAHs, were found in the oil
      samples collected from both automobiles even at a short driving distance after
      oil change. The concentrations of total PAH in lubricating oil collected from two
      automobiles driven for a longer distance after oil change were very similar.

PMID- 11291448
TI  - Chemical composition and ecophysiological responses of Empetrum nigrum to
      aboveground element application.
AB  - Empetrum nigrum L. (crowberry) is one of the plants surviving near the Cu-Ni
      smelters in Finland and Russia. According to field observations, the fine roots
      of E. nigrum are situated below 40 cm depth and the root biomass is reduced in
      the polluted sites. This could cause a reduced root uptake of macronutrients and
      trace elements in the field and, therefore, the possible element uptake by
      aboveground parts of E. nigrum was studied in a greenhouse. Six different
      treatment solutions containing various heavy metal and macronutrient
      concentrations were applied to the stems and leaves of E. nigrum and the chemical
      composition and ecophysiological parameters were measured. Heavy metal
      concentrations in the leaves and stem bark, and Cu concentrations in the stems,
      increased with increasing metal concentrations in the spraying solutions. The
      bark and leaves had higher heavy metal concentrations than the stems of
      comparable age classes. The macronutrient and Mn concentrations in E. nigrum did
      not change significantly with increasing element concentrations in the spraying
      solution. Neither the stem water potential nor the leaf chlorophyll
      concentrations showed any clear response to element applications. Therefore, the
      element uptake by aboveground parts of E. nigrum was not confirmed by this study.
      However, there was a tendency to a decrease in CO2 exchange rate and increase in
      foliar abscisic acid content in plants treated with the highest element
      concentrations.

PMID- 11291449
TI  - Differential responses of benthic microbes and meiofauna to fish-farm disturbance
      in coastal sediments.
AB  - Bacterial and meiofaunal abundance and biomass and their response to the
      disturbance induced by fish-farm biodeposition were investigated from March to
      October 1997 on a monthly basis at two stations of the Gaeta Gulf (Tyrrhenian
      Sea, Mediterranean Sea). The biopolymeric fraction of the organic matter was
      characterized by high concentrations which was similar at both fish-farming
      impacted and control stations. Similarly, bacteria accounted for a small fraction
      of the biopolymeric organic carbon (< 1%), while the contribution due to auto
      fluorescent cell biomass (i.e. prokaryotic and eukaryotic cells displaying auto
      fluorescence) to the total biopolymeric carbon was quantitatively negligible (<
      0.1%). Benthic bacteria appear to be sensitive to organic enrichment as their
      abundance increased significantly beneath the cage, whilst numbers of meiofauna
      was lower than in the control. Changes occurred also in terms of individual
      nematode biomass that increased as result of the biodeposition. A particularly
      useful tool appeared to be represented by the ratio of benthic auto-fluorescent
      cells to bacterial abundance, bacteria to meiofaunal biomass and auto-fluorescent
      cells to meiofauna biomass. All these parameters described well the impact due to
      biodeposition on the benthic environment as their ratios displayed significantly
      higher values in farm sediments, but recovered rapidly (15 days) to values
      observed in the control (i.e. undisturbed conditions) immediately after cage
      removal. Changes observed in the present study highlight that the increased
      organic loading determined a shift of the relative contribution of the different
      benthic components to the total biopolymeric carbon, so that in highly impacted
      systems total benthic biomass becomes increasingly dominated by microbial
      components.

PMID- 11291450
TI  - Element distribution in Empetrum nigrum microsites at heavy metal contaminated
      sites in Harjavalta, western Finland.
AB  - Small-scale element distribution in soil-plant-systems in patches of Empetrum
      nigrum (microsites) at heavy metal contaminated sites located 0.5 and 4 km from
      the copper-nickel smelter at Harjavalta was investigated. The Cu concentrations
      of E. nigrum varied between 12 and 2300 mg/kg dw and showed increasing
      accumulation with increasing tissue age. Stems contained more Cu than leaves of
      the same age. The distribution pattern of Ni and Pb in the above-ground biomass
      followed that of Cu. Roots contained relatively low concentrations of all
      airborne heavy metals. In the soil, the highest concentrations of total Cu
      occurred in the humus (Oh) layer: on average 49,450 mg/kg dw at 0.5 km distance
      and 12,025 mg/kg dw at 4.0 km. Despite the extremely high Cu concentrations in
      the topsoil, the concentrations in the mineral soil below a depth of 10 cm did
      not exceed 2.5 mg/kg dw at any site.

PMID- 11291451
TI  - Marine oil pollution and beached bird surveys: the development of a sensitive
      monitoring instrument.
AB  - One of the most obvious adverse effects of (chronic) pollution of the world's
      oceans and seas with mineral oil is the mortality of seabirds. Systematic surveys
      of beachcast corpses of birds ('beached bird surveys') have been used in many
      parts of the world to document the effect of oil pollution, but particularly so
      in Western Europe and in parts of North America. In this paper, the history,
      current schemes, methods and possible (future) use of beached bird surveys are
      described and discussed, because the value of beached bird surveys has been hotly
      disputed. Oil pollution is known since the late 19th century, while the first
      beached bird surveys were conducted in the 1920s. Due to the amount of man-power
      needed for these surveys, most beached bird survey programs thrived only through
      the work of a large number of volunteers. However, most programs have resulted in
      substantial amounts of high quality data, often covering many consecutive years.
      One of the main shortcomings of many beached bird survey programs was the
      emphasis on stranded bird numbers rather than on relative measures, such as oil
      rates (percentage of corpses oiled of all corpses found). Sources of pollution,
      particularly so in chronically polluted regions such as the North Sea, the
      Baltic, the Mediterranean and the waters around Newfoundland, are insufficiently
      known, but could be studied through a sampling program connected to beached bird
      surveys. Suggestions for standardization of methods are presented, which could
      lead to a global and highly sensitive monitoring instrument of marine oil
      pollution.

PMID- 11291452
TI  - Heavy metals removal in fixed-bed column by the macro fungus Pycnoporus
      sanguineus.
AB  - The ability of Pycnoporus sanguineus to adsorb heavy metals from aqueous solution
      was investigated in fixed-bed column studies. The experiments were conducted to
      study the effect of important design parameters such as column bed height, flow
      rate and initial concentration of solution. The breakthrough profiles were
      obtained in these studies. A mathematical model based on external mass transfer
      and pore diffusion was used for the prediction of mass transfer coefficient and
      effective diffusivity of metals in macro-fungi bed. Experimental breakthrough
      profiles were compared with the simulated breakthrough profiles obtained from the
      mathematical model. Bed Depth Service Time (BDST) model was used to analyse the
      experimental data and evaluated the performance of biosorption column. The BDST
      model parameters needed for the design of biosorption columns were evaluated for
      lead, copper and cadmium removal in the column. The columns were regenerated by
      eluting the metal ions using 0.1 M hydrochloric acid solution after the
      adsorption studies. The columns were subjected to repeated cycles of adsorption
      of same metal ions and desorption to evaluate the removal efficiency after
      adsorption-desorption.

PMID- 11291453
TI  - Mercury content in roach (Rutilus rutilus L.) in circumneutral lakes--effects of
      catchment area and water chemistry.
AB  - The environmental influence on the mercury content in roach (Rutilus rutilus L.)
      is investigated using partial least square regression on 46 environmental
      variables describing the land use in the catchment area, various catchment area
      and lake characteristics, lake water chemistry, and fish stock. The Hg content in
      the fish from the 78 investigated circumneutral lakes is heavily influenced by
      the land use in their surroundings. The boreal forest lakes possessed the highest
      Hg levels in roach, whereas fish from lakes surrounded by arable land had lower
      levels. The Hg levels also showed a negative relationship to the amount of
      dissolved ions and the total amount of nutrients in lake water. Lake pH did not
      have any significant influence on the Hg content in roach in these non-acidified
      lakes. The Hg levels in lakes influenced by large amounts of wetland were less
      well explained by the presently investigated environmental variables, which
      implies that the Hg burden in fish from this kind of lake is governed by other
      factors.

PMID- 11291454
TI  - The effects of crude oil and the effectiveness of cleaner application following
      oiling on US Gulf of Mexico coastal marsh plants.
AB  - Field studies were conducted in two different marsh habitats in Louisiana coastal
      wetlands to evaluate the effects of oiling (using South Louisiana Crude oil, SLC)
      and the effectiveness of a shoreline cleaner (COREXIT 9580) in removing oil from
      plant canopies. The study sites represented two major marsh habitats; the
      brackish marsh site was covered by Spartina patens and the freshwater marsh was
      covered by Sagittaria lancifolia. Field studies were conducted in each habitat
      using replicated 5.8 m2 plots that were subjected to three treatments; oiled
      only, oiled + cleaner (cleaner was used 2 days after oiling), and a control.
      Plant gas exchange responses, survival, growth, and biomass accumulation were
      measured. Results indicated that oiling led to rapid reductions in leaf gas
      exchange rates in both species. However, both species in 'oiled + cleaned' plots
      displayed improved leaf conductance and CO2 fixation rates. Twelve weeks after
      treatment initiation, photosynthetic carbon fixation in both species had
      recovered to normal levels. Over the short-term, S. patens showed more
      sensitivity to oiling with SLC than S. lancifolia as was evident from the data of
      the number of live shoots and above-ground biomass. Above-ground biomass remained
      significantly lower than control in S. patens under 'oiled' and 'oiled + cleaned'
      treatments while it was comparable to controls in S. lancifolia. These studies
      indicated that the cleaner removed oil from marsh grasses and alleviated the
      short-term impact of oil on gas exchange function of the study plants. However,
      use of cleaner had no detectable effects on above-ground biomass production or
      regeneration at the end of the first growing season in S. patens. Similarly, no
      beneficial effects of cleaner on carbon fixation and number of live shoots were
      apparent beyond 12 weeks in S. lancifolia.

PMID- 11291455
TI  - PM10 pollution episodes as a function of synoptic climatology in a mountainous
      industrial area.
AB  - In this study an attempt is made to investigate the prevailing meteorological
      conditions during days with high concentrations of PM10 (particles with diameter
      < 10 microns), collected in the Eordea mountain basin. This is an industrial area
      in the northwestern mountainous region of Greece. Over the 4-year data-gathering
      period, the days in which the United States Environmental Protection Agency 24-h
      PM10 standard was exceeded (episode days), were identified in relation to
      prevailing synoptic scale and local meteorological conditions. The results
      indicated that days with increased PM10 concentrations in this area can be
      grouped into four categories in relation to their synoptic circulation
      characteristics. The highest concentrations were found to be associated with
      stagnant conditions. Under these conditions, local circulations developed in the
      area, resulting in recirculation and accumulation of pollutants.

PMID- 11291456
TI  - Lead contamination of seabirds harvested with lead shot--implications to human
      diet in Greenland.
AB  - Lead contamination of seabirds from the use of lead shot in Greenland was studied
      in thick-billed murre hunted at Nuuk in November 1998. In each bird shot pellets
      were located and counted using X-ray. The birds were skinned and viscera, head,
      wings and legs removed, after which the carcass was cooked. The soup and breast
      meat were then analyzed for lead after removal of visible shot pellets. In the
      soup the lead concentration was quite low, mean 6.3 micrograms/l (95% confidence
      interval between 4.4 and 8.2 micrograms/l), whereas breast meat lead values have
      a mean of 0.22 microgram/g (wet weight basis; 95% confidence interval between
      0.10 and 0.36 microgram/g). This is more than 10 times higher than in birds not
      killed with lead shot. We found no correlation between lead concentration
      measured and number of pellets recorded in the whole bird or in the soup or in
      meat. The study indicates that lead in the meat exists as small lead fragments,
      left during the passage of pellets through the breast. Because of inhomogeneous
      lead distribution in samples, the uncertainty of estimated lead concentration in
      breast meat is high. Based on this study, it is concluded that birds killed with
      lead shot are a significant source of lead, probably the most important single
      source, of the diet of many people in Greenland. We estimate an intake of 50
      micrograms lead from eating one boiled murre with soup. In addition people will
      occasionally eat whole lead shot pellets which have documented health effects. An
      intake of 50 micrograms lead is about twice as much as the daily average lead
      intake from all dietary sources in Denmark, about 25 times the daily lead intake
      from other marine food items in Greenland, and about one-fourth of the accepted
      tolerable daily intake.

PMID- 11291457
TI  - Trends in organochlorine residue concentrations and burdens in grey seals
      (Halichoerus grypus) from Sable Is., NS, Canada, between 1974 and 1994.
AB  - In blubber from maternal grey seals (Halichoerus grypus) from Sable Is., NS,
      sigma DDT (p,p'-DDE and p,p'-DDT) concentrations declined from 12 micrograms/g
      lipid in 1974 to 0.5 microgram/g in 1994. Pup blubber sigma DDT concentrations
      were about 60% of those of their mothers, and declined at similar rates. In
      maternal seals, p,p'-DDE increased from 56% sigma DDT in 1974 to 89% in 1994.
      Polychlorinated biphenyl concentrations did not change between 1976 and 1988, but
      then declined; the relative proportion of chlorobiphenyl (CB) 101 increased, and
      those of CBs 170 and 187 decreased between 1985 and 1991. Concentrations of alpha
      hexachlorocyclohexane and trans-nonachlor declined after 1988, and of
      oxychlordane after 1992; concentrations of hexachlorobenzene were constant
      between 1984 and 1994.

PMID- 11291458
TI  - Influence of oil contamination levels on hydrocarbon biodegradation in sandy
      sediment.
AB  - The influence of oil concentration on hydrocarbon biodegradation in a sandy
      sediment was studied in polyvinyl chloride reactors (0.45 x 0.28 x 0.31 m)
      containing 76.8 kg of beach sand in natura, where the upper layer was
      artificially contaminated with petroleum. The oil-degrading microorganisms used
      consisted of a mixed culture named ND, obtained from landfarming and associated
      with indigenous microorganisms. On the 28th day of the process, the degradation
      in reactors containing sandy sediment contaminated with light Arabian oil and
      presenting an initial oil content of 14, 21 or 28 g kg-1 reached the following
      levels (%): 33.7, 32.9 and 28.9 for oil and grease; up to 88.3, 35.3 and 13.0 for
      C14-C26 n-alkanes; and 100, 61.3 and 59.4 for pristane, respectively. Phytane
      removal (37.1%) was only detected in the reactor contaminated with the lowest oil
      concentration studied. These results, together with the expressive bacterial
      growth observed (from 10(6) to 10(11) cfu g-1) give strong support to the
      argument that biodegradation was the dominant component of the remediation
      process. Susceptibility to biodegradation was inversely proportional to
      increasing oil contamination. The degradation of branched alkane: pristane was
      not repressed by the presence of n-alkanes.

PMID- 11291459
TI  - Intermediate care: private-public partnership.

PMID- 11291460
TI  - Why doctors should think more carefully before prescribing.

PMID- 11291461
TI  - Atopic dermatitis in childhood.
AB  - Atopic dermatitis (eczema) is the commonest of the childhood dermatoses,
      accounting for 20% of all dermatological referrals with many cases continuing
      into adulthood. The morbidity and costs to society are high.

PMID- 11291462
TI  - Treatment of vascular naevi in children.
AB  - This article will summarize the treatment options available for the two commonest
      vascular birthmarks of childhood: port wine stains and capillary haemangiomas.
      The treatment of port wine stains is primarily cosmetic and performed with
      lasers. The treatment of capillary haemangiomas is needed for both cosmetic and
      medical reasons and can include lasers, corticosteroids, interferons and surgery.

PMID- 11291463
TI  - The urinary catheter: 'a-voiding catastrophe'.
AB  - A quarter of all patients admitted to hospital are catheterized. This is
      associated with significant morbidity and occasional mortality. This article
      reviews the risks of urinary catheterization and suggests preventative measures.

PMID- 11291464
TI  - Infliximab: a new treatment for rheumatoid arthritis.
AB  - Infliximab, a chimeric mouse human monoclonal antibody, is an anti-TNF treatment
      for rheumatoid arthritis. In the past there was a sizeable group of people who
      had exhausted disease-modifying antirheumatic drugs (DMARDs) and were left
      largely untreated. This has been revolutionized by treatments such as infliximab
      which have been shown to be effective for patients in whom standard DMARDs have
      failed.

PMID- 11291466
TI  - The tracheostomy tube change: a review of techniques.
AB  - Tracheostomy tube changing is a routine procedure. However, occasional problems
      can arise and result in fatalities. This article reviews the various measures and
      techniques used to optimize the safeguarding of the airway during a tracheostomy
      tube change, including the 'railroad' technique. The management of accidental
      decannulations is also reviewed.

PMID- 11291465
TI  - Marfan's syndrome: a review.
AB  - Marfan's syndrome is an inherited disorder of connective tissue, in which the
      most pronounced abnormalities occur in the musculoskeletal, cardiovascular and
      ocular systems. Aortic dilatation and dissection are the major causes of
      morbidity and mortality. Recent advances in surgical techniques and earlier
      intervention have reduced postoperative mortality and morbidity.

PMID- 11291467
TI  - Evidence-based medicine: putting theory into practice.
AB  - Evidence-based medicine is an essential tool to ensure the effective and
      efficient management of patients. A practical and unbiased assessment of clinical
      evidence can be achieved by asking simple questions about the data. Undertaking
      this process can reveal a new perspective on traditional treatment approaches.

PMID- 11291468
TI  - Advanced nurse practitioners and physician assistants: what is the difference?
      Comparing the USA and UK.
AB  - With the reduction in junior doctors' hours and fewer doctors being trained in
      the UK, there is a need for other types of health-care practitioners to fill the
      gap. This article describes some of the background to the present situation and
      delineates two types of roles, the advanced nurse practitioner and the physician
      assistant, for consideration as alternatives to address the present and growing
      shortage of doctors.

PMID- 11291469
TI  - How to write a peer review.
AB  - The peer review process is a quality control for scientific publication. Well
      done, it helps editors to improve their journals and protects readers from
      wasting time on ill-conceived, redundant, irrelevant or erroneous literature.
      Badly done it can act as an obstacle to innovation. This article tells you how to
      be a first rate peer reviewer.

PMID- 11291470
TI  - An unusual rash and end-stage renal failure.

PMID- 11291471
TI  - Toxic megacolon: remember cytomegalovirus.

PMID- 11291472
TI  - Malignant transformation of a solitary enchondroma.

PMID- 11291473
TI  - The acute abdomen.

PMID- 11291474
TI  - The future of pathology in the UK.

PMID- 11291475
TI  - Acute gastric distension: a lesson from the classics.

PMID- 11291476
TI  - Model coupling intraparticle diffusion/sorption, nonlinear sorption, and
      biodegradation processes.
AB  - Diffusion, sorption and biodegradation are key processes impacting the efficiency
      of natural attenuation. While each process has been studied individually, limited
      information exists on the kinetic coupling of these processes. In this paper, a
      model is presented that couples nonlinear and nonequilibrium sorption
      (intraparticle diffusion) with biodegradation kinetics. Initially, these
      processes are studied independently (i.e., intraparticle diffusion, nonlinear
      sorption and biodegradation), with appropriate parameters determined from these
      independent studies. Then, the coupled processes are studied, with an initial
      data set used to determine biodegradation constants that were subsequently used
      to successfully predict the behavior of a second data set. The validated model is
      then used to conduct a sensitivity analysis, which reveals conditions where
      biodegradation becomes desorption rate-limited. If the chemical is not pre
      equilibrated with the soil prior to the onset of biodegradation, then fast
      sorption will reduce aqueous concentrations and thus biodegradation rates.
      Another sensitivity analysis demonstrates the importance of including nonlinear
      sorption in a coupled diffusion/sorption and biodegradation model. While
      predictions based on linear sorption isotherms agree well with solution
      concentrations, for the conditions evaluated this approach overestimates the
      percentage of contaminant biodegraded by as much as 50%. This research
      demonstrates that nonlinear sorption should be coupled with diffusion/sorption
      and biodegradation models in order to accurately predict bioremediation and
      natural attenuation processes. To our knowledge this study is unique in studying
      nonlinear sorption coupled with intraparticle diffusion and biodegradation
      kinetics with natural media.

PMID- 11291477
TI  - Stochastic-convective transport with nonlinear reaction and mixing: application
      to intermediate-scale experiments in aerobic biodegradation in saturated porous
      media.
AB  - Aerobic biodegradation of benzoate by Pseudomonas cepacia sp. in a saturated
      heterogeneous porous medium was simulated using the stochastic-convective
      reaction (SCR) approach. A laboratory flow cell was randomly packed with low
      permeability silt-size inclusions in a high permeability sand matrix. In the SCR
      upscaling approach, the characteristics of the flow field are determined by the
      breakthrough of a conservative tracer. Spatial information on the actual location
      of the heterogeneities is not used. The mass balance equations governing the
      nonlinear and multicomponent reactive transport are recast in terms of reactive
      transports in each of a finite number of discrete streamtubes. The streamtube
      ensemble members represent transport via a steady constant average velocity per
      streamtube and a conventional Fickian dispersion term, and their contributions to
      the observed breakthroughs are determined by flux-averaging the streamtube solute
      concentrations. The resulting simulations were compared to those from a high
      resolution deterministic simulation of the reactive transport, and to alternative
      ensemble representations involving (i) effective Fickian travel time distribution
      function, (ii) purely convective streamtube transport, and (iii) streamtube
      ensemble subset simulations. The results of the SCR simulation compare favorably
      to that of a sophisticated high-resolution deterministic approach.

PMID- 11291478
TI  - Dimension reduction and source identification for multispecies groundwater
      contamination.
AB  - Assessment of chemical contamination at large industrial complexes with long and
      sometimes unknown histories of operation represents a challenging environmental
      problem. The spatial and temporal complexity of the contaminant may be due to
      changes in production processes, differences in the chemical transport, and the
      physical heterogeneity of the soil and aquifer materials. Traditional mapping
      techniques are of limited value for sites where dozens of chemicals with diverse
      transport characteristics may be scattered over large spatial areas without
      documentation of disposal histories. In this context, a site with a long and
      largely undocumented disposal history of shallow groundwater contamination is
      examined using principal component analysis (PCA). The dominant chemical groups
      and chemical "modes" at the site were identified. PCA results indicate that five
      primary and three transition chemical groups can be identified in the space of
      the first three eigenvectors of the correlation matrix, which account for 61% of
      the total variance of the data. These groups represent a significant reduction in
      the dimension of the original data (116 chemicals). It is shown that each group
      represents a class of chemicals with similar chemo-dynamic properties and/or
      environmental response. Finally, the groups are mapped back onto the site map to
      infer delineation of contaminant source areas for each class of compounds. The
      approach serves as a preliminary step in subsurface characterization, and a data
      reduction strategy for source identification, subsurface modeling and remediation
      planning.

PMID- 11291479
TI  - Determining effective interfacial tension and predicting finger spacing for DNAPL
      penetration into water-saturated porous media.
AB  - The difficulty in determining the effective interfacial tension limits the
      prediction of the wavelength of fingering of immiscible fluids in porous media. A
      method to estimate the effective interfacial tension using fractal concepts was
      presented by Chang et al. [Water Resour. Res. 30 (1994) 125]. We modified the
      method in that the macroscopic interface length was used instead of the system
      width. Methods to determine the macroscopic and the microscopic interface length
      are given. Lab experiments of dense nonaqueous phase liquid (DNAPL) penetrating
      into water-saturated glass beads were carried out in a two-dimensional (2-D)
      transparent chamber. The displacement processes were recorded using a 35-mm
      camera or a video camera, which was directly connected to and controlled by a
      computer. Unlike the method of Chang et al. (1994), the modified method used here
      gives a constant value of the effective interfacial tension over time. The
      predicted wavelengths of fingering are relatively close to those observed except
      for the fine beads.

PMID- 11291480
TI  - Analyses of locally measured bromide breakthrough curves from a natural gradient
      tracer experiment at Krauthausen.
AB  - Solute travel time distributions were derived from breakthrough curves (BTCs) of
      bromide concentrations, which were measured during a large-scale tracer
      experiment in a quaternary fluviatile aquifer at Krauthausen. Travel time
      distributions to a specific point in the aquifer were derived from locally
      measured BTCs, using averaged absolute concentrations cabs(x1,t), normalized
      concentrations cnorm(x1,t), and velocity-weighted normalized concentrations
      cvw(x1,t). The travel time distributions were characterized in terms of
      equivalent convective-dispersive transport parameters: the equivalent solute
      velocity and equivalent dispersivity. Parameters were derived from BTCs using
      moment analyses and least-squares fits of the 1-D convection-dispersion equation
      (CDE). Both local and averaged BTCs showed pronounced tailing which was not well
      described by the 1-D CDE and which indicates the presence of macroscopic regions
      with low velocities in the aquifer. Therefore, dispersivities derived from CDE
      fits were significantly smaller than those derived from time moments. The BTCs of
      cabs(x1,t) were dominated by only a few local BTCs with high concentrations and
      were less representative for the travel time distribution than BTCs of averaged
      normalized concentrations. Dispersivities derived from cnorm(x1,t) and cvw(x1,t)
      were very similar. Finally, estimates of dispersivities and vertical correlation
      length of lnK, gamma 3, from BTCs were in agreement with a first-order estimate
      of the dispersivity and gamma 3 based on grain size data and flow meter
      measurements.

PMID- 11291481
TI  - Biosurfactant-enhanced solubilization of NAPL mixtures.
AB  - Remediation of nonaqueous phase liquids (NAPLs) by conventional pump-and-treat
      methods (i.e., water flushing) is generally considered to be ineffective due to
      low water solubilities of NAPLs and to mass-transfer constraints. Chemical
      flushing techniques, such as surfactant flushing, can greatly improve NAPL
      remediation primarily by increasing the apparent solubility of NAPL contaminants.
      NAPLs at hazardous waste sites are often complex mixtures. However, the
      equilibrium and nonequilibrium mass-transfer characteristics between NAPL
      mixtures and aqueous surfactant solutions are not well understood. This research
      investigates the equilibrium solubilization behavior of two- and three-component
      NAPL mixtures (containing akylbenzenes) in biosurfactant solutions. NAPL
      solubilization is found to be ideal in water (i.e., obeys Raoult's Law), while
      solubilization in biosurfactant solutions was observed to be nonideal.
      Specifically, the relatively hydrophobic compounds in the mixture experienced
      solubility enhancements that were greater than those predicted by ideal enhanced
      solubilization theory, while the solubility enhancements for the relatively
      hydrophilic compounds were less than predicted. The degree of nonideality is
      shown to be a nonlinear function of the NAPL-phase mole fraction. Empirical
      relationships based on the NAPL-phase mole fraction and/or micelle-aqueous
      partition coefficients measured in single-component NAPL systems are developed to
      estimate values for the multicomponent partition coefficients. Empirical
      relationships that incorporate both the NAPL-phase mole fraction and single
      component partition coefficients yield much improved estimates for the
      multicomponent partition coefficient.

PMID- 11291482
TI  - Eulerian derivation of the fractional advection-dispersion equation.
AB  - A fractional advection-dispersion equation (ADE) is a generalization of the
      classical ADE in which the second-order derivative is replaced with a fractional
      order derivative. In contrast to the classical ADE, the fractional ADE has
      solutions that resemble the highly skewed and heavy-tailed breakthrough curves
      observed in field and laboratory studies. These solutions, known as alpha-stable
      distributions, are the result of a generalized central limit theorem which
      describes the behavior of sums of finite or infinite-variance random variables.
      We use this limit theorem in a model which sums the length of particle jumps
      during their random walk through a heterogeneous porous medium. If the length of
      solute particle jumps is not constrained to a representative elementary volume
      (REV), dispersive flux is proportional to a fractional derivative. The nature of
      fractional derivatives is readily visualized and their parameters are based on
      physical properties that are measurable. When a fractional Fick's law replaces
      the classical Fick's law in an Eulerian evaluation of solute transport in a
      porous medium, the result is a fractional ADE. Fractional ADEs are ergodic
      equations since they occur when a generalized central limit theorem is employed.

PMID- 11291484
TI  - For one town, a Triad side effect. Purchase of Quorum may leave N.D. town with
      one acute-care hospital.

PMID- 11291483
TI  - A functional relation for field-scale nonaqueous phase liquid dissolution
      developed using a pore network model.
AB  - A pore network model with cubic chambers and rectangular tubes was used to
      estimate the nonaqueous phase liquid (NAPL) dissolution rate coefficient,
      Kdissai, and NAPL/water total specific interfacial area, ai. Kdissai was computed
      as a function of modified Peclet number (Pe') for various NAPL saturations (SN)
      and ai during drainage and imbibition and during dissolution without
      displacement. The largest contributor to ai was the interfacial area in the water
      filled corners of chambers and tubes containing NAPL. When Kdissai was divided by
      ai, the resulting curves of dissolution coefficient, Kdiss versus Pe' suggested
      that an approximate value of Kdiss could be obtained as a weak function of
      hysteresis or SN. Spatially and temporally variable maps of Kdissai calculated
      using the network model were used in field-scale simulations of NAPL dissolution.
      These simulations were compared to simulations using a constant value of Kdissai
      and the empirical correlation of Powers et al. [Water Resour. Res. 30(2) (1994b)
      321]. Overall, a methodology was developed for incorporating pore-scale processes
      into field-scale prediction of NAPL dissolution.

PMID- 11291485
TI  - Soon a field of three. AmeriSource, Bergen Brunswig latest to plan merger.

PMID- 11291486
TI  - Hospital industry's March madness. Six systems across the nation launch massive
      restructuring strategies.

PMID- 11291487
TI  - Praise HIPAA. Some providers embrace privacy regulations in hopes of securing
      long-term savings.

PMID- 11291488
TI  - Allina under fire. Minn. AG alleges lavish spending by not-for-profit.

PMID- 11291489
TI  - Telling it like it is. Young Executive of the Year thrives in tough job by
      playing it straight.

PMID- 11291490
TI  - Foreign affairs. Survey shows small but growing emphasis on attracting overseas
      patients.

PMID- 11291491
TI  - Emergence medicine. New venture capital fund to focus on developing nations in
      Europe.

PMID- 11291492
TI  - It's Scully at last. After long delay, Bush taps Federation of American Hospitals
      chief to lead HCFA.

PMID- 11291493
TI  - Hanging on, reaching out. AHA pushes to boost Medicare payments by another $17
      billion.

PMID- 11291494
TI  - Hospitals' fears are realized. Spending bill would use Medicare surplus for drug
      benefit, reform effort.

PMID- 11291495
TI  - Physician income trends vary by specialty.

PMID- 11291496
TI  - Preventive care. Whose job is improvement?

PMID- 11291497
TI  - Time to roll out 'disruptive innovation'.

PMID- 11291498
TI  - Credentialing--important, but difficult.

PMID- 11291499
TI  - A comparison of diabetes patient's self-reported health status with hemoglobin
      A1c test results in 11 California health plans.
AB  - PURPOSE: To examine the relationship between hemoglobin A1c (HbA1c) test rates
      and values and various self-reported measures of health status within a sample of
      diabetes patients drawn from 11 California health plans, with a focus on
      improving diabetes care in this patient population. DESIGN: The analysis relies
      on data obtained from medical records of a sample population of 4,747 diabetes
      patients and a patient survey mailed to a large subsample of patients included in
      the medical-records analysis. METHODS: Descriptive methods were used to compare
      the medical records and survey-data results. PRINCIPAL FINDINGS: There were
      substantive differences noted between diabetes patients' self-reported health
      status, their level of satisfaction with the care they received, and the actual
      care they received. There was a large discrepancy between diabetes patients'
      perceptions of the care they received for their diabetes, which was
      overwhelmingly positive, and the HbA1c test-frequency rates observed across the
      11 health plans studied, which were low. CONCLUSIONS: Patients' self-reports of
      health status, satisfaction with care, and extent of control over diabetes--a
      chronic condition that may have few perceptible symptoms--are associated with
      significant methodological limitations. Our examination of the relationship
      between perceived levels of self-management of diabetes and test status indicated
      that for patients who had at least one HbA1c test, some education during that
      process may have resulted in behavioral change. Patients who received no tests,
      however, may remain unaware of their glycemic control and the long-term
      consequences associated with even mild hyperglycemia. A clear need thus exists to
      educate diabetes patients about their health status. Health plan and provider
      group investments in educational efforts aimed at increasing testing rates are
      likely to lead to improved glycemic control and a reduction in the incidence of
      diabetes-related complications and related expenditures.

PMID- 11291501
TI  - Premiums outstrip medical costs for first time in 6 years.

PMID- 11291500
TI  - 'Final' Stark regulations still a work in progress.

PMID- 11291502
TI  - Take an inside look at the rate-setting process.

PMID- 11291503
TI  - Can you measure up to these hospital performance benchmarks.

PMID- 11291504
TI  - Chart your utilization patterns against these national data.

PMID- 11291505
TI  - HMO enrollment, penetration rates reveal surprises.

PMID- 11291506
TI  - How the media influences women's perceptions of health care.
AB  - To better understand the effectiveness of media sources that marketers use to
      channel direct-to-consumer (DTC) campaigns to women, researchers devised a study
      that segmented the female participants according to their degree of involvement
      in health care decisions, marital status, age, employment, income, and education.
      The findings show that women in certain population segments reacted far
      differently to health care information depending on whether it was presented
      through the Internet, magazines, newspapers, radio, or TV.

PMID- 11291507
TI  - Moving from defined benefits to defined contributions.
AB  - The concept of "defined contributions" has become one of the hottest topics in
      health care financing today. The traditional defined benefits system offered all
      employees essentially the same set of health benefits, regardless of individual
      circumstances. The defined contributions approach would offer some or all of the
      premium dollars to the employee to spend on various options chosen from a much
      expanded list of benefits. When adopted, this user-initiated approach will have
      far-reaching implications for health care marketing.

PMID- 11291508
TI  - The challenge of marketing managed care.

PMID- 11291509
TI  - AHA reality check takes the pulse of health care consumers.

PMID- 11291510
TI  - Defining the benefits of online medical market research.

PMID- 11291511
TI  - E-marketing on a shoestring.

PMID- 11291512
TI  - NationsHealth introduces Web-based data distribution.

PMID- 11291513
TI  - Marketing to the consumer: perspectives from the pharmaceutical industry.
AB  - Individualized health management is one of the most exciting challenges facing
      health care marketing today. Greater access to health information has empowered
      consumers to take more control of their health needs, creating a whole new
      landscape for marketers, manufacturers, and service providers. Customization is
      the key to creating marketing campaigns that successfully target today's health
      conscious consumers. Drawing on individualized market intelligence and available
      genetic information, pharmaceutical companies are learning to tailor products to
      meet the needs of this growing market.

PMID- 11291514
TI  - Pregnancy and lactation in relation to vaccines and antibodies.

PMID- 11291515
TI  - Immunization and organ transplant donors and recipients.

PMID- 11291516
TI  - Overcoming immunization disparities based on ethnicity.

PMID- 11291517
TI  - Targeting vaccines based on underlying disease states.

PMID- 11291518
TI  - Somebody else's antibodies: the characteristics and roles of immune globulins.
AB  - CREDIT: This lesson is good for 0.2 CE units, with a passing grade of 70%.
      OBJECTIVES: After completing this continuing education article, the pharmacist
      will be able to: 1. Compare and contrast active vs. passive immunity and
      homologous vs. heterogenous antibodies. 2. Describe the historical development
      and modern manufacture of immune globulins. 3. Identify the wide range of uses
      and effects of modern immune globulin products. 4. Discuss the adverse effect
      profiles of currently available immune globulins.

PMID- 11291519
TI  - Survey of standards and guidelines for immunization delivery.
AB  - CREDIT: This lesson is good for 0.2 CE units, with a passing grade of 70%.
      OBJECTIVES: After completing this continuing education article, the pharmacist
      will be able to: 1. Compare and contrast active vs. passive immunity and
      homologous vs. heterogenous antibodies. 2. Describe the historical development
      and modern manufacture of immune globulins. 3. Identify the wide range of uses
      and effects of modern immune globulin products. 4. Discuss the adverse effect
      profiles of currently available immune globulins.

PMID- 11291520
TI  - Timely public health data drive prevention efforts.

PMID- 11291521
TI  - Dashboards help gauge impact of clinical guidelines.
AB  - The Western Psychiatric Institute and Clinic turns to dashboard to help identify
      the effects of guidelines in a behavioral health setting.

PMID- 11291522
TI  - Doing risk assessment without clinical data.
AB  - That only works in the movies. For those who want to construct health care
      services, it's necessary to know where the potential users are and get them to
      the site. Here's a strategy for doing that that doesn't involve costly risk
      assessment tasks.

PMID- 11291523
TI  - Is Web-based consumer health assessment the new wave?
AB  - GlaxoSmithKline pursues online headache pain assessment. A health assessment tool
      developed by John E. Ware Jr. is tailored for an individual's experience with
      headache pain and produces a report tailored for physicians.

PMID- 11291524
TI  - Web cooperative brings medical groups together.
AB  - It's not necessary to develop your own website to have a presence on the
      Internet. A large number of health care organizations have banded together to
      form their own global village.

PMID- 11291525
TI  - Progress in the biology of psychiatry.

PMID- 11291526
TI  - Candidate gene studies in psychiatric disorders: promises and limitations.

PMID- 11291527
TI  - Quantitative electroencephalography in Alzheimer's disease: comparison with a
      control group, population norms and mental status.
AB  - OBJECTIVE: Given that quantitative electroencephalography (EEG) has repeatedly
      shown excessive slow wave activity in dementia of the Alzheimer type (DAT) that
      increases with disease progression, we assessed the clinical utility of this tool
      by comparing various approaches used to assess slowing. DESIGN: Cross-sectional
      study comparing quantitative EEG data from patients with DAT with normative data
      from an elderly control group and from EEG norms derived from a large population.
      PARTICIPANTS: 35 subjects diagnosed with probable DAT and 30 elderly controls.
      OUTCOME MEASURE: EEG recorded from 21 scalp sites of each patient and elderly
      control during vigilance-controlled, eyes-closed, resting conditions was
      spectrally analyzed to yield measures of absolute and relative power in delta,
      theta, alpha and beta bands and indices of mean alpha band and total band
      frequency. RESULTS: Group comparisons of raw or age-regressed z-score population
      normative values yielded different profiles with respect to direction of
      frequency band changes, regional topography and clinical rating correlations, but
      both procedures evidenced overall patterns of EEG slowing in DAT. However, both
      methodologies yielded only modest (75%) classification rates. CONCLUSION:
      Quantitative EEG remains a valuable research tool but, as yet, an unproven
      diagnostic tool, for DAT.

PMID- 11291528
TI  - Protein kinase C beta II mRNA levels decrease in the striatum and cortex of
      transgenic Huntington's disease mice.
AB  - Huntington's disease (HD) is caused by the inheritance of the huntingtin gene
      with an expanded CAG repeat. The function of the normal or mutant form of the
      huntingtin protein remains to be determined. We used differential display to
      determine differences in steady-state mRNA levels between wild-type and the R6/2
      transgenic mouse model of HD. Using this method, we determined that the steady
      state mRNA levels of protein kinase C beta II (PKC beta II) subunit are decreased
      in symptomatic HD mice compared with age-matched wild-type controls. The decrease
      in PKC beta II mRNA levels occurred in both the striatum and cortex. Previously,
      it had been demonstrated that PKC beta II immunoreactivity is decreased in the
      caudate-putamen of patients with Huntington's disease. PKC has been implicated in
      the long-term potentiation model of brain plasticity and learning, and the loss
      of PKC may affect information storage in HD. The expression of htt-HD throughout
      the brain affects the transcription of specific genes in regions not associated
      with widespread neurodegeneration.

PMID- 11291529
TI  - Performance of patients with schizophrenia on the Wisconsin Card Sorting Test
      (WCST).
AB  - OBJECTIVE: To directly compare the performance of patients with schizophrenia and
      control subjects on the Wisconsin Card Sorting Test (WCST). Specifically, we
      sought to verify if there are significant differences on the "classical" WCST
      measurements (perseverative errors and number of categories), as well as on more
      rarely reported scores, and assess the extent to which patients with
      schizophrenia can improve their performance with card-by-card instructions and
      continuous verbal reinforcement. DESIGN: Prospective cross-sectional study.
      SETTING: Psychiatry department in a university-affiliated hospital. PARTICIPANTS:
      30 patients with schizophrenia, diagnosed according to DSM-IV criteria, and 30
      control subjects, matched to patients according to age and education.
      INTERVENTION: The WCST was administered according to the criteria of Heaton, and
      a subgroup of the patients with schizophrenia was given a retest after an
      explanation of the WCST and verbal reinforcements. RESULTS: Patients with
      schizophrenia succeeded on fewer categories (t = 23.3, p < 0.001), committed more
      perseverative errors (t = 15.6, p < 0.001), made more perseverative responses (t
      = 14.6, p < 0.001), needed more trials to succeed at the first category (t = 9.2,
      p < 0.003) and gave significantly lower conceptual level responses (t = 14.1, p <
      0.001) than the controls. However, on retest, patients with schizophrenia
      committed significantly fewer perseverative errors (t = 5.1, p < 0.001) and
      showed higher conceptual level responses (t = -3.45, p < 0.003). CONCLUSION:
      Consistent with a hypothesis of frontal dysfunction in schizophrenia, patients
      with schizophrenia tend to show a perseverative deficit; however, some are able
      to partially overcome this deficit when given verbal reinforcement.

PMID- 11291530
TI  - Influence of novel and conventional antipsychotic medication on subjective
      quality of life.
AB  - OBJECTIVE: To assess the impact of novel antipsychotic medication on the
      subjective quality of life of patients with schizophrenia and schizoaffective
      disorders. DESIGN: Retrospective, cross-sectional analysis of data from 2 studies
      conducted in 1997 and 1998. PATIENTS: 91 outpatients (50 men and 41 women, mean
      age 43.3 years) diagnosed with schizophrenia (n = 70) and schizoaffective
      disorder (n = 21); the mean Global Assessment of Functioning score for these
      patients was 48.0 (standard deviation 12.5). OUTCOME MEASURE: Patients were
      categorized into 1 of 3 groups: those taking conventional (n = 41), novel (n =
      26) or mixed (both conventional and novel) (n = 24) antipsychotics. Responses on
      the Satisfaction with Life Domains Scale were used to assess subjective quality
      of life. RESULTS: The type of antipsychotic medication taken did not influence
      satisfaction with life scores; in fact, 2 items dealing with social relationships
      were scored lower by those taking novel antipsychotics. CONCLUSIONS: Patients
      taking novel antipsychotics may expect more from life, and this might explain
      their lower quality-of-life scores.

PMID- 11291532
TI  - Selective serotonin reuptake inhibitors and discontinuation symptoms.

PMID- 11291533
TI  - Gynecomastia induced by treatment with tandospirone, a 5-HT1A agonist.

PMID- 11291534
TI  - B chromosomes in two fish species, genus Rhamdia (Siluriformes, Pimelodidae).
AB  - Specimens belonging to two fish species genus Rhamdia were cytogenetically
      analysed from seven localities in Brazil and Argentina. In addition to the 58
      chromosomes of the basic karyotype, one to five metacentric B chromosomes were
      observed carrying conspicuous heterochromatic blocks on the distal regions of
      both chromosome arms. These B chromosomes are mitotically stable and, in the two
      best-sampled populations in R. hilarii (Lobo and 29 reservoirs), they showed
      frequency distributions fitting a binomial distribution, though Bs were more
      frequent in the latter. The presence of B chromosomes with the same appearance in
      R. quelen suggests an ancient origin for these B chromosomes, presumably prior to
      speciation from a common ancestor.

PMID- 11291531
TI  - Neuropsychological change in patients with schizophrenia after treatment with
      quetiapine or haloperidol.
AB  - OBJECTIVE: To assess the efficacy of quetiapine, a recently introduced second
      generation antipsychotic medication, in reducing cognitive impairment in patients
      with schizophrenia. DESIGN: Prospective, randomized, double-blind clinical trial.
      PATIENTS: 25 patients who met the Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition, (DSM-IV) criteria for schizophrenia were recruited
      from 3 Canadian hospitals. INTERVENTION AND OUTCOME MEASURES: After a 48-hour
      washout period, 25 patients with schizophrenia were randomly assigned to double
      blind treatment with quetiapine or haloperidol for 6 months and evaluated with
      rating scales for psychotic symptoms, mood and extrapyramidal side effects, as
      well as standardized neuropsychological measures sensitive to 6 cognitive
      domains: fine motor skill, attention span, verbal reasoning and fluency,
      visuospatial construction and fluency, executive skills and visuomotor tracking,
      and immediate recall of verbal and nonverbal materials. The measures were
      repeated 8 weeks and 6 months after treatment was initiated. RESULTS: Quetiapine
      improved psychosis and mood without inducing extrapyramidal symptoms. Quetiapine
      also had beneficial effects on cognitive skills, particularly verbal reasoning
      and fluency skills and immediate recall, with additional improvements on
      executive skills and visuomotor tracking and on the average of the 6 cognitive
      domains with sustained treatment. Patients taking haloperidol showed improvements
      in general clinical status, but no specific improvements on the positive
      syndrome, the negative syndrome, depression ratings or cognitive skills.
      CONCLUSIONS: These preliminary results support the potential value of quetiapine
      for improving cognitive impairment in patients with schizophrenia and emphasize
      the importance of further research with this promising atypical antipsychotic.

PMID- 11291535
TI  - Karyological investigations on seven weevil species (Coleoptera, Curculionidae).
AB  - Karyological studies were carried out on seven Palaearctic weevils. The following
      chromosome numbers were found in individual species, i.e. Otiorhynchus niger
      (F.), Phyllobius viridearis (Laich.), Phyllobius scutellaris Redt., Phyllobius
      calcaratus (F.), Polydrusus cervinus (L.), and Brachyderes incanus (L.) 2n = 22,
      n Male = 10 + Xyp, in Lixus elegantulus (Boh.) 2n = 22, n Male = 21 + Xyp. The
      heterochromosomes of all the examined species form, in the first meiotic
      metaphase, a typical parachute bivalent.

PMID- 11291536
TI  - C-banding patterns in chromosomes of Paederius rubrothoracicus carpathicola
      Scheerpetz 1957 (Coleoptera, Staphylinidae: Paederinae).
AB  - An analysis was made of the C-banded karyotype of Paederius rubrothoracicus
      carpathicola Scheerp. The result indicates that the chromosome number is 2n = 36
      and n Male = 17 + Xyp. The examined karyotype shows a paracentromeric position of
      constitutive heterochromatin in all autosomes. The y chromosome is wholly
      euchromatic.

PMID- 11291537
TI  - Some aspects of karyotype of Liarina (Orthoptera: Tettigoniidae, Agraeciini) from
      Vietnam.
AB  - Karyotypes (chromosome number and shape) of four species of the subtribe Liarina
      were studied. The chromosome numbers and NF (Fundamental Number) in this group of
      species range from 2n Male = 33 (34) to 27(30): Liaromorpha buonluoiensis 2n Male
      = 33 (34), Sialaiana transiens 2n Male = 29 (34), Liara tramlapensis 2n Male = 29
      (32), and Anelytra (Perianelytra) propria 2n Male = 27 (30). Cyto-taxonomy
      analysis indicates an intensive karyotype evolution among species belonging to
      three different groups of the genera. Differences of karyotypes are connected
      with Robertsonian fusion and tandem fusion in autosomes. Additionally, C-banding
      distribution and location of the NORs were studied.

PMID- 11291538
TI  - Chromosome evolution in the genus Poecilimon (Orthoptera, Tettigonioidea,
      Phaneropteridae).
AB  - Cytotaxonomic analysis of 20 species and subspecies of the genus Poecilimon using
      C-banding pattern, chiasma frequency, and morphometric characteristics of the
      chromosomes were described. Using a cladistic analysis the chromosome data
      provided a basis to produce a phylogenetic tree which was compared with a tree
      based on morphological characters and DNA sequence data. There are important
      differences in the grouping of data sets to species obtained on the basis of
      morphology/DNA analyses and that based on chromosomes. The explanation of the
      differences between C-banding patterns and taxonomic proximity is probably that
      the C-banding pattern changes quickly as the result of the high degree of
      variation of constitutive heterochromatin.

PMID- 11291539
TI  - Predetermination of cytokinesis and transition from holoblastic to partial
      superficial cleavage in early embryonic development of Tetrodontophora
      bielanensis (Collembola).
AB  - In the T. bielanensis embryo, only karyokinesis occurs during the first cleavage
      division, and a two-nuclear syncytial embryo forms. Then, two cytoplasmic
      concentrations in the form of elongated rolls perpendicular to each other develop
      below the periplasm at the animal pole of the egg. The second cleavage division
      is also associated with karyokineses only. After the embryo reaches the four
      nuclear stage, cytokinesis occur at its animal pole, and two cleavage furrows
      perpendicular to each other develop in the periplasm above the cytoplasmic
      concentrations. The cell membranes forming within the furrows do not invade the
      cytoplasmic concentrations, but their growing tips push them into the egg
      interior, where they merge and form the central cytoplasmic concentration. The
      developing cell membranes do not invade the central cytoplasm; they band and grow
      above its surface. Four pyramidal blastomeres form as a result of this. The eight
      blastomere embryo forms through both karyokinesis and cytokinesis, but the
      growing cell membranes now band below the previous ones and cut off anucleate
      parts of the mother blastomeres, which fuse with the central cytoplasm. Thus,
      during this phase of development the transition from holoblastic to partial
      superficial cleavage is initiated. Morphological analysis suggests that the
      formation of the first two cytokinesis is predetermined by and depends on factors
      connected with the animal pole periplasm. It also suggests that the central
      cytoplasm constitutes the morphological field, inducing the transition from
      holoblastic to partial superficial cleavage.

PMID- 11291540
TI  - Microorganisms resistant to heavy metals and toxic chemicals as indicators of
      environmental pollution and their use in bioremediation.
AB  - Microorganisms present in water samples from various industrial effluents were
      analysed for their resistance to lead, chromium, and cadmium. The ability of
      these microorganisms to grow on or metabolize toxic hydrocarbons and pesticides
      was also checked. Microorganisms in samples from the steel and tanning industries
      were generally resistant to metal ions but were not capable of metabolizing toxic
      hydrocarbons. Conversely, microorganisms found in samples of pesticide and from
      the chemical industry were capable of metabolizing hydrocarbons and pesticides
      but were not much resistant to metal ions. Microorganisms from effluents of the
      paint industry and urban wastes were resistant to lead. A correlation between the
      population of microorganisms and the type of pollution was observed. Indigenous
      microorganism could be regarded as indicators of pollution and be used in various
      operations to resist, process, metabolize, and detoxify toxic industrial wastes.

PMID- 11291541
TI  - Paramecium aurelia species complex in a natural but newly reconstructed pond of
      the Botanical Garden of the Jagiellonian University in Krakow.
AB  - In a natural but newly reconstructed pond the presence of P. biaurelia was
      revealed. The previous studies conducted in 1992 did not reveal the occurrence of
      any species of the Paramecium aurelia complex here.

PMID- 11291542
TI  - Mitochondrial DNA sequence from an extinct population of European vendace,
      Coregonus albula L.
AB  - Nucleotide sequence of the mitochondrial DNA control region was determined for
      the formalin-preserved specimen of the individual European vendace, Coregonus
      albula, belonging to an extinct population. The specimen has been preserved and
      stored in formalin for 39 years. A comparison with two previously determined
      sequences obtained for specimens from other populations of vendace revealed both
      nucleotide substitutions and site heteroplasmy. The ability to sequence DNA from
      formalin-preserved museum specimens of rare or extinct taxa provides another
      sampling strategy for phylogenetic studies on fish.

PMID- 11291543
TI  - Stanislaw Skowron (1900-1976). The 100th anniversary of his birth.
AB  - The article recollects a biography of Professor Stanislaw Skowron, distinguished
      Polish embryologist, geneticist, and evolutionist, known particularly well to all
      those working in the field of regeneration. In 1953 Professor S. Skowron founded
      and became the first editor of FOLIA BIOLOGICA an international quarterly journal
      of biological research devoted mainly to experimental zoology. He is also
      remembered as an eminent lecturer and excellent teacher of many generations of
      physicians, pharmacists, and biologists. A comprehensive list of his publications
      has been assembled and printed for the first time.

PMID- 11291544
TI  - Adaptative role of carotenoids and carotenoproteins in Cyclops kolensis
      Lilljeborg (Crustacea: Copepoda) specimens to extremely eutrophical conditions.
AB  - The authors, using column, thin-layer, and ion-exchange chromatography,
      investigated carotenoid and carotenoprotein complex content in Cyclops kolensis
      specimens from an extremely eutrophic pond. The following carotenoids were found
      to be present: beta-carotene, beta-cryptoxanthin, lutein epoxide, crustaxanthin,
      4'-hydroxyechinenone, canthaxanthin, and astaxanthin. Carotenoprotein complex
      containing astaxanthin as the prosthetic group name gamma-crustacyanine was
      purified from Cyclops kolensis individuals examined. The authors justify the
      adaptative role of these pigments in Cyclops kolensis specimens in extremely
      eutrophical conditions.

PMID- 11291545
TI  - Glycogen distribution in porcine fallopian tube epithelium during the estrus
      cycle.
AB  - Histochemical features of two different parts of the porcine Fallopian tube have
      been studied, with special reference to cyclic changes in the distribution of
      glycogen particles. Porcine Fallopian tubes were obtained from a local
      slaughterhouse. Slides were studied under light microscopy utilising histological
      and histochemical techniques. The most striking feature during the periovulatory
      stage of the estrus cycle was the occurrence of glycogen granules in the apical
      cytoplasm of epithelial cells in both the ampulla and isthmus of the Fallopian
      tubes. In the isthmus, cells containing numerous granules of polysaccharides
      aggregated into areas of different sizes were noted after ovulation. During the
      midluteal phase their number was minimal or were even absent. In the ampula
      typical extrusion of secretory granules and nuclei protruding into the tubal
      lumen was visible after ovulation. In the luteal phase a lot of nuclei protruded
      into the tubal lumen and some free in the lumen were noted. It is possible that
      glycogen in the preovulatory stage functions as a source of energy for ciliary
      movement and as a nourishment for the ovum. In the isthmus large number of
      aggregated glycogen particles was observed also after ovulation. In this stage of
      the cycle, numerous granules of polysaccharide aggregated in isthmus epithelium
      could be the major energy source for embriogenesis when the embryo travels down
      the Fallopian tubes, during the early cleavage stage.

PMID- 11291546
TI  - Time and reproductive phase-dependent effects of exogenous melatonin on the
      pineal gland and ovary of a nocturnal bird, the Indian spotted owlet, Athene
      brama.
AB  - In a tropical nocturnal bird, the Indian spotted owlet, Athene brama, the
      intraperitonial injection of an identical amount (20 mg/100 g b. wt/day) of
      exogenous melatonin (MEL) for 15 consecutive days increased the pineal weight and
      plasma MEL level in sexually active birds while it decreased them in inactive
      birds more potently when injected in the evening (18.30-19.30 h) rather than the
      morning (0500-0600 h). On the other hand, more efficiently than the morning hour
      treatment, the evening hour MEL injection decreased the ovary weight and plasma
      estradiol and progesterone levels both in sexually active and inactive birds, but
      more potently in active than inactive birds. Thus, the exogenous MEL showed the
      time and reproductive phase dependent effects on the pineal gland and the ovary
      of this nocturnal bird.

PMID- 11291547
TI  - The presence of acetylcholinesterase-positive nerve fibres in the deep pineal
      gland and the pineal stalk but not in the superficial part of adult albino rats.
AB  - Application of the histochemical method for testing acetylcholinesterase (AChE,
      EC 3.1.1.7) showed the presence of AChE-positive nerve fibers in the deep pineal
      gland and the pineal stalk but not in the superficial part of adult albino rats.
      These findings may indirectly support the existence of the potentially
      cholinergic innervation of at least some of the rat pinealocytes present in these
      parts of the gland and augment the evidence of the heterogeneity of the rat
      pinealocytes. It is possible that cholinergic neurons in the medial habenular
      nuclei or in the parasympathetic sphenopalatine ganglion may be a source of these
      AChE-positive fibres. The examination was performed at the light microscope
      level.

PMID- 11291548
TI  - Paclitaxel, cisplatin, and concurrent radiation for esophageal cancer.
AB  - Paclitaxel is an active agent for adenocarcinomas and squamous cell carcinomas of
      the esophagus and is a radiation sensitizer. We sought to investigate the
      toxicity and complete response rate of paclitaxel, cisplatin, and concurrent
      radiation for esophageal cancer. Forty-one patients with esophageal cancer were
      studied, 29 with adenocarcinomas and 12 with squamous cell cancers. Twelve
      patients had tumor extension into the proximal stomach and/or abdominal
      adenopathy. Patients received paclitaxel 60 mg/m2 by 3-hour intravenous (i.v.)
      infusion, and cisplatin 25 mg/m2 weekly on days 1, 8, 15, and 22. Radiation was
      administered concurrently to a total dose of 39.60 Gy, in 1.80 Gy fractions, for
      22 treatments. Patients with medical or surgical contraindications to
      esophagectomy received 2 additional weeks of paclitaxel with a radiation boost to
      50.4 Gy. Neutropenia was the most common grade 3/4 toxicity occurring in 10
      patients (24%). Only 2 patients (5%) had grade 4 esophagitis requiring parenteral
      nutrition. Twelve patients (29%) obtained a complete response. The 2-year
      progression-free and overall survival rates were 40% and 42%, respectively.
      Esophagitis was less severe than expected and prophylactic enteral feeding tubes
      were not necessary. Additional effective systemic treatments are needed to reduce
      the development of distant metastases.

PMID- 11291549
TI  - Free will, autonomy, and patient noncompliance in Judaism.

PMID- 11291550
TI  - Website review.

PMID- 11291551
TI  - A randomized, double-blind trial of famciclovir versus acyclovir for the
      treatment of localized dermatomal herpes zoster in immunocompromised patients.
AB  - In this randomized, double-blind, multicenter, acyclovir-controlled study, the
      efficacy and safety of famciclovir were evaluated for the treatment of herpes
      zoster in patients who were immunocompromised following bone marrow or solid
      organ transplantation or oncology treatment. A total of 148 patients, 12 years or
      older with clinical evidence of localized herpes zoster, received either oral
      famciclovir, 500 mg three times daily, or acyclovir, 800 mg five times daily, for
      10 days. Famciclovir was equivalent to acyclovir with respect to the numbers of
      patients reporting new lesion formation while on therapy (77% vs. 73%,
      respectively). There were no significant differences between the groups in the
      time to cessation of new lesion formation, full crusting, complete healing of
      lesions, or loss of acute phase pain. Treatment with famciclovir was well
      tolerated, with a safety profile comparable to that of acyclovir. Thus oral
      famciclovir is a convenient, effective, and well-tolerated regimen for
      immunocompromised patients with herpes zoster.

PMID- 11291552
TI  - Malignant fibrous histiocytoma: an institutional review.
AB  - BACKGROUND: A thorough understanding of malignant fibrous histiocytoma (MFH), the
      most common subtype of soft tissue sarcoma, will lead to improved histologic
      specific protocols. METHODS: 126 patients with histologically confirmed MFH were
      analyzed. The median follow-up was 42 months (range 1-233 months). RESULTS:
      Overall survival was 58% at 5 years and 38% at 10 years. Grade significantly
      influenced prognosis, with 10-year survival of 90%, 60%, and 20% for low,
      intermediate, and high grade tumors, respectively (p = 0.0007). Distant
      metastases at initial presentation (p = 0.0002) and size of the primary tumor (p
      = 0.0007) influenced outcome. Neither anatomic site nor depth of the primary
      tumor were significant prognostic factors. Positive microscopic margins were
      associated with a decreased disease-free survival (p = 0.006). CONCLUSIONS: Tumor
      grade, size, and distant metastases at initial presentation remain the most
      important prognostic factors for MFH. Resection with negative microscopic margins
      decreased the incidence of local recurrence.

PMID- 11291553
TI  - Gene expression of insulin-like growth factors and receptors in neoplastic
      prostate tissues: correlation with clinico-pathological parameters.
AB  - The insulin-like growth factor (IGF) system has been shown to regulate prostate
      cancer cell growth in vitro and, possibly, in vivo. In this study we examined RNA
      expression of IGF ligands and their receptors in 23 paired benign and neoplastic
      prostate tissues. In addition to comparing gene expression of IGF ligands and
      receptors between benign and neoplastic tissue samples, we correlated IGF-I, IGF
      II, IGFR-1, and IGFR-2 RNA levels in tumor samples with prognostic clinico
      pathological parameters such as stage, grade, Gleason score, perineural or
      extraprostatic invasion. We found higher IGF-I RNA levels in benign vs. malignant
      tissues (p = 0.014), whereas IGF-II RNA expression was higher in tumors with high
      Gleason score (GS) (p = 0.045). Using the Spearman rank correlation test we also
      found a positive correlation between IGFR-2 RNA levels and GS (p = 0.01). No
      correlation was found between expression of IGF ligands and receptors and tumor
      grade, stage perineural invasion, or extraprostatic involvement. We conclude that
      differential expression of certain IGF system components may be important in the
      biology and clinical behavior of prostate cancer.

PMID- 11291554
TI  - Effect of TNP-470 (AGM-1470) on the growth of rat rhabdomyosarcoma tumors of
      different sizes.
AB  - Potential anticancer therapy with the fumagillin analog TNP-470 was investigated
      in the present project using subcutaneously growing rhabdomyosarcomas in rats.
      Specifically, influences of different tumor sizes at the start of treatment as
      well as dose/schedules were evaluated with this angiogenesis inhibitor. The
      results show a significant (p = < or = 0.01) reduction of the growth rate, even
      for relatively large-sized (> 7 cm3) tumors, when 50 mg/kg TNP-470 was used every
      other day for up to 3 or 5 injections. With 30 mg/kg TNP-470 injections, effects
      were seen only with tumors measuring < 7 cm3. The histologic examinations
      demonstrate an increase in necrosis, both in the center and in the peripheral
      part of TNP-470-treated tumors. Overall, both tumor volume and drug dose
      determine treatment outcome with the rat rhabdomyosarcoma. The results suggest
      that angiogenesis inhibitors could represent a valid component in the treatment
      of progressive tumor growth, also of large tumors as often encountered in
      clinics. The antivasculature therapy might also improve hypoxia/necrosis-related
      therapeutic approaches.

PMID- 11291555
TI  - High-dose chemotherapy with bone marrow rescue for high-grade gliomas in adults.
AB  - High-grade malignant gliomas are inevitably fatal, despite every effort to
      improve this prognosis, including various radiotherapeutic modalities, radio- and
      chemotherapeutic associations, and combinations of several drugs. High-dose
      chemotherapy and autologous bone-marrow transplantation (ABMT) have been
      increasingly used in the last 10 years for solid tumors, and several phase II
      studies in high-grade glioma patients have been conducted in the setting of both
      adjuvant treatment and recurrent disease. The most frequently used drug in the
      conditioning regimens in BCNU at doses higher than that employed by other
      regimens in other pathologies (800-1000 mg/m2). These dosages involve a high
      toxicity that is not balanced by a significant improvement in survival. New drugs
      and/or regimens must be tested in randomized trials.

PMID- 11291556
TI  - Herceptin: from the bench to the clinic.

PMID- 11291557
TI  - Screening for sources of interindividual pharmacokinetic variability in
      anticancer drug therapy: utility of population analysis.

PMID- 11291558
TI  - The role of genetic factors in the etiology of pancreatic adenocarcinoma: an
      update.
AB  - Pancreatic cancer is a disease with a very poor prognosis and its etiology is
      still largely elusive. The only consistent environmental risk factor is cigarette
      smoking. A previous history of pancreatitis or diabetes mellitus is also
      considered to be a risk factor. Epidemiological studies have confirmed that
      relatives of those with pancreatic cancer have an increased risk of this
      malignancy, and it has been evaluated that 3-5% of all pancreatic cancer cases
      are caused by genetic predisposition to the disease. Usually this occurs in the
      setting of a known inherited cancer syndrome caused by mutations in genes such as
      BRCA1/2 and CDKN2A. Whether or not a true site-specific pancreatic adenocarcinoma
      syndrome exists is not known. The real challenge for the management of high risk
      patients is to develop new screening methods than can identify pre-neoplastic or
      early neoplastic lesions in a timely manner.

PMID- 11291559
TI  - Recent advances in bladder cancer chemotherapy.

PMID- 11291560
TI  - Inhibition of vascular endothelial growth factor by octreotide in colorectal
      cancer patients.
AB  - Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis
      and for the growth of colorectal cancer; thus its inhibition can arrest tumor
      growth and decrease metastatic potential. Octreotide has been shown to inhibit
      growth of colorectal tumors in vitro and in vivo. Part of the antiproliferative
      activity of octreotide could be related to its antiangiogenic properties. Effects
      of octreotide on VEGF expression were evaluated in 35 patients with operable
      colorectal cancer receiving octreotide for 2 weeks before surgery. Tissue VEGF
      expression and serum VEGF concentrations were determined before and after
      treatment with octreotide. There was a statistically significant reduction in the
      tissue VEGF expression both considering the percentage of VEGF positive cells (P
      = 0.006) and the intensity of VEGF staining (P = 0.003). A similar significant
      reduction was observed in serum values of VEGF (P = 0.03). The present study
      indicates that octreotide inhibits expression of VEGF in colorectal cancer
      patients, and, furthermore, that serum VEGF expression correlates with tissue
      VEGF, representing a safe method to monitor the activity of antiangiogenic
      agents.

PMID- 11291561
TI  - Quality improvement efforts in oncology: are we ready to begin?
AB  - Large variations in the quality of cancer care are a matter of concern in the
      United States. Despite spending over 15% of our GNP on health care, more than any
      other country in the world, some cancer patients face significant risks of dying
      from their treatment precisely because of their choice of physician. The
      Institute of Medicine has reported that variations in the quality of cancer are
      large, and that low-experienced providers are more likely to provide a lower
      quality of medical care. Increased pressures to contain costs have led to concern
      that the quality and outcomes of cancer care may only worsen. One reaction to
      this situation is a greater reliance on "report cards." In an effort to address
      both quality and cost issues, providers are looking outside the health care
      sector for guidance for more acceptable alternatives to report cards, which are
      often viewed as punitive. The approach that they most often have selected
      recently is termed continuous quality improvement (CQI) or total quality
      management (TQM). In this article, we describe the potential benefits and
      drawbacks of CQI efforts in oncology, review experiences with four different CQI
      cancer programs, and make recommendations about future CQI efforts.

PMID- 11291562
TI  - Monitoring and improving quality of cancer care: easy to recommend, difficult to
      accomplish.

PMID- 11291563
TI  - Genetics of pancreatic cancer.

PMID- 11291564
TI  - Adenocarcinoma of the stomach in an adolescent presenting as pneumoperitoneum: a
      brief report.
AB  - BACKGROUND: Adenocarcinoma of the stomach is rare in children and adolescents. A
      unique case, presenting as an acute abdomen with pneumoperitoneum, is discussed.
      METHODS: Case presentation and literature review. RESULTS: A 13-year-old girl
      with perforated gastric adenocarcinoma treated by wedge resection developed
      metastatic disease within two months and died within six months despite
      chemotherapy. CONCLUSION: Frozen section of all perforated gastric ulcers, with
      resection/postoperative chemotherapy for adenocarcinoma. SUMMARY: A 13-year-old
      girl with gastric adenocarcinoma presented with pneumoperitoneum. Within two
      months of wedge resection widespread metastatic disease was documented by
      computerized tomography scan and laparoscopy and despite chemotherapy, the
      patient died within six months. Frozen section of all perforated gastric ulcers,
      even in children, and definitive formal gastrectomy with postoperative
      chemotherapy, offer the only chance of cure.

PMID- 11291565
TI  - An electronic survey of physicians using online clinical discussion groups: a
      brief report.
AB  - INTRODUCTION: Online discussion groups are a relatively new form of informal
      communication among physicians. Physicians' Online, an Internet-based medical
      information and communication network with a current membership base that
      includes more than 200,000, United States physicians, contains extensive bulletin
      board discussion areas with more than 47,000 topics posted to date. There are no
      published data available regarding the characteristics and behaviors of the
      individuals who participate in these discussions. METHODS: To better characterize
      the users of these groups, in March 1998, we posted an eight-question, multiple
      choice electronic survey on Physicians' Online's home page inviting users of the
      clinical discussion groups to participate. RESULTS: We analyzed responses from
      586 participants. The most common characteristics were: urban and Northeastern
      United States location, age less than 55 years, clinical practice of internal
      medicine or one of its subspecialties, private solo or single/multispecialty
      group practice, and reported weekly consultation with three or less colleagues.
      Most physicians were interested in specific clinical cases. Forty-one percent of
      the respondents chose to read discussion groups only but rarely or never
      initiated or responded. CONCLUSIONS: Younger age, urban setting, private
      practice, and infrequent consultation with colleagues were the most common
      characteristics found among users of Physicians' Online's online clinical
      discussion groups. That specific clinical cases were the most common interest
      speaks to the notion that discussion groups may represent an attractive resource
      for helping to manage clinical cases. Future research should explore in greater
      depth the demographics of users, specific motivations for physician use, ways to
      improve active participation, and the impact on clinical practice.

PMID- 11291566
TI  - Witness to the birth of cardiovascular surgery. A personal memoir--Part One of
      Two.

PMID- 11291567
TI  - The high-performance physician: disruptive technological solutions to ensure
      compliance, productivity, and profitability.

PMID- 11291568
TI  - Iatrogenic error and physician responsibility.
AB  - The recent report on iatrogenic errors highlighted the scope of the problem and
      suggested solutions including a national agency to oversee error reporting. This
      may or may not occur; in the meantime physicians are not relieved of their
      responsibility to respond to the issue of patient safety. Reasons for the slow
      response to date are discussed and suggestions for the future are offered.

PMID- 11291569
TI  - Sexually selected traits and adult survival: a meta-analysis.
AB  - Traits correlated with male mating success are likely to be subject to sexual
      selection. Sexually selected characters are thought to be costly to develop and
      maintain. If males do not vary their investment in sexual traits in relation to
      their ability to bear the costs, there should be a negative relationship between
      male longevity or survival and the expression of sexual traits. In particular, a
      negative relationship is predicted by pure Fisherian models for the evolution of
      sexual ornaments. The same should also be true for traits that evolve via
      pleiotropy (e.g., due to sensory exploitation or bias) with no subsequent
      evolution of condition dependent modification. We collected information on the
      relationship between traits correlated with male mating rate and estimates of
      adult male survivorship or life span. In total we obtained 122 samples from 69
      studies of 40 species of bird, spider, insect, and fish. In a meta-analysis we
      calculated the average sample size weighted correlation between trait expression
      and adult survival. Analyses at the level of samples, studies, and species
      revealed significant positive relationships (r = 0.08, 0.10, and 0.13,
      respectively; all P < 0.001). The unweighted correlation at the species level was
      r = 0.24. In general, males with larger ornaments or weapons, greater body size,
      or higher rates of courtship showed greater survivorship or longevity. This
      finding is inconsistent with pure Fisherian models or other models that do not
      incorporate condition or quality dependent trait expression. It suggests that
      male investment in sexually selected traits is not fixed but varies in relation
      to the ability to pay the underlying costs of expressing these characters. Hence,
      many secondary sexual characters are likely to be condition dependent in their
      expression.

PMID- 11291570
TI  - The science of Louis Pasteur: a reconsideration.

PMID- 11291571
TI  - [Extracellular hydrolytic enzymes and their relevance during Candida albicans
      infections].
AB  - Candida albicans cannot only infect skin and mucosa, but can also cause life
      threatening systemic candidosis. While natural barriers and the immune system of
      healthy individuals normally prevent such infections, virulence factors exist
      that enable C. albicans to survive on surfaces and the permit the fungus to
      invade tissues and organs in immunocompromised patients. Adhesions factors,
      morphological flexibility and hydrolytic enzymes belong to this group of
      virulence factors.C.albicans appears to be able to use these specific virulence
      attributes at distinct stages of an infection or  in different types of
      candidosis. For example, distinct adhension factors are important for the
      persistence of    C. albicans on mucosal epithelial cells, while other factors
      are necessary for the adhesion to endothelial tissue. The differential expression
      of specific virulence factors at different stages of an infection could be the
      reason why C. albicans not only has single genes for extracellular hydrolytic
      enzymes, but gene families. Both secreted aspartate proteinases (Saps) and
      secreted lipases (Lips) from C. albicans are encoded by at least 10 different
      genes. This high number of similar genes might empower C. albicans with the
      ability to secrete a specific and appropriate enzymatic response at distinct
      stages of an infection. For both gene families  differential expression has been
      shown in vitro and in vivo, which would be reasonable for such an adaptation.
      Expression studies revealed that distinct SAP and LIP genes were expressed under
      conditions when potential subtrates ( proteins or lipids) were not present in the
      growth medium. Such expression patterns would imply that these genes may have
      functions other than  simply providing nutrients for the fungus. The specific
      transcription of single SAP genes  during the course of an infection suggests
      that these genes may have specific functions during different stages of an
      infection. In fact, inhibition studies and  the use of mutants with targeted gene
      disruptions showed  that distinct SAP genes (SAP1-3) are important durning
      infections of skin and mucosa, while others (SAP4-6) are most relevant for
      systemic infections.

PMID- 11291572
TI  - [Invasive aspergillosis on a surgical intensive care unit].
AB  - From 1-1-1995 until 1-3-2000 4777 patients were treated in a surgical intensive
      care unit. 12 patients (10 male/2 female, mean age 58 years) suffered from
      invasive aspergillosis. One patient had a purulent descending mediastinitis with
      evidence of Aspergillus fumigatus in the mediastinum and in both pleural
      cavities. One patient got a right upper lobectomie in cause of an aspergilloma.
      In 10 patients a broncho-alveolar aspergillosis was proved by at least two
      cultures from broncho-alveolar lavage (BAL) and biopsies. All our patients had a
      mean of 12.8 risk factors for systemic mycoses. The patients suffered from
      following underlying diseases: 3 x carcinoma of the esophagus (chemotherapy +
      radiation), 2 x ulcerative colitis, 1 x rupture of the aorta with insufficiency
      of the liver, 1 x acute leucosis and 1 x purulent mediastinitis. The therapy was
      based on infusion with amphotericin B up to 1.5 mg/kg/day in combination with
      flucytosine or itraconazole. In 4 patients inhalation of amphotericin B aerosol
      was applied. After therapeutic failure of amphotericin B-therapy 3 patients got
      voriconazole according to a study protocol. 10 patients died, 7 of them from
      their underlying disease.

PMID- 11291573
TI  - [Monascus purpureus: a new fungus of allergenic relevance].
AB  - Anaphylactic reactions to food containing allergens in the consumption or
      preparation of food are well known. However, allergy in the preparation of
      sausages have rarely been described. In the present study a 26-year-old butcher
      was investigated who had a severe anaphylactic reaction developing sneezing,
      rhinitis, conjunctivitis, generalised pruritus, followed by widespread urticaria,
      Quincke's oedema and dyspnoe after starting to prepare sausages containing red
      yield rice. Red yield rice is produced from polished and washed rice by means of
      the fungus Monascus purpureus. It was the first time that Monascus purpureus
      could be shown as allergic agent by means of prick-to-prick test, Cellular
      Antigen Stimulation Test (CAST) and different other immunoblots.

PMID- 11291574
TI  - [Scedosporiosis of the brain with fatal outcome after traumatizatio of the foot.
      case report].
AB  - A 33 year old German man suffered from a wound of his foot after an accident. He
      developed an osteomyelitis. From wound probes Scedosporium apiospermum could be
      isolated for several times. Some weeks later a cerebral lesion could be
      diagnosed. The lesion was extirpated and again S. apiospermum could be cultured
      from the cerebral probes. A few weeks later the patient died and some new
      cerebral lesions could be diagnosed by CT-scan.

PMID- 11291575
TI  - [Evaluation of a panfungal pcr assay for the diagnosis of pneumocystis carinii
      pneumonia (pcp)].
AB  - We compared a universal fungal PCR assay with fluorescence microscopy for the
      diagnosis of Pneumocystis carinii pneumonia. 82 bronchoalveolar lavages (BALs) of
      64 immunocompromised patients with atypical pneumonia and 50 BALs of 50
      immunocompetent adults without lung disease were examined. 10 immunocompromised
      patients were clinically and/or histologically proven to suffer from PCP. For
      fluorescence microscopy, sensitivity and specificity in detecting P. carinii were
      80.0% and 98.1%, for the PCR assay 100.0% and 96.2%, respectively. The PCR assay
      is a useful method for the diagnosis of PCP and is recommended as an additional
      test to microscopical methods.

PMID- 11291576
TI  - [What's new in diagnosis and therapy of dermatomycoses in childhood].
AB  - Mycotic infections in childhood are caused in the majority of cases by
      dermatophytes. If an oral treatment is indicated, itraconazole and terbinafine
      are superior to griseofulvin and are nowadays drugs of first choice although an
      official registration for treatment of children is missing in Germany. Yeasts in
      infections of childhood are the causative organisms in Pityrosporum-folliculitis
      and act as an important co-factor in diaper dermatitis.

PMID- 11291577
TI  - [Antifungal susceptibility testing in chronically recurrent vaginal candidosis as
      basis for effective therapy].
AB  - The chronically recidivist vulvo-vaginal candidiasis is one of the most stubborn
      problematic diagnosis in the dermatology and gynaecology ward. Prognosis and
      therapy are primarily determined by the causative micro-organism and the
      interaction of the fungal species with the currently available antifungal agents.
      Objective of the study was the investigation of vaginal yeast isolates from
      patients with chronically recidivist vaginal candidiasis against 8 antifungal
      agents with the aim of optimising the standard therapy with azole antifungal
      agents and assessment of alternative therapy schemes. 55 clinical isolates
      (Dermatology, Charite) of 40 patients were tested by microdilution according to
      DIN 58940-84. Species differentiation and identification was performed by Fourier
      Transform Infrared Spectroscopy (FTIR). In the result Candida glabrata was the
      predominant causative agent for the recidivist vaginal candidiasis. MIC-mode
      values for C. glabrata were: fluconacole 32 micrograms/ml, itraconacole 1
      microgram/ml, ketoconacole 1 microgram/ml, amphotericine B, voriconacole 0.03
      microgram/ml, amphotericin B 0.5 microgram/ml, terbinafine 128 micrograms/ml,
      cicloproxolamine 4 micrograms/ml, 5-fluorocytosine 0.03 microgram/ml. Some
      strains of Patients with suboptimal introductory low doses of fluconacole showed
      increasing of MIC in course of therapy. Parallel resistance with itraconacole was
      observed in all these cases. Consecutively isolated strains could be clearly and
      reliably identified by FTIR. In conclusion of most importance is the initial dose
      adapatation of the drug used, e.g. for fluconacole 800/d p.o., when C. glabrata
      is the causative agent. Low dose fluconacole therapy is always unsuccessful in
      recurrent vaginal candidiasis and induces secondary resistance. Demonstrated high
      susceptibility of voriconacole, amphotericine B an 5-fluorocytosine particularly
      for C. glabrata may indicate of an anitmycotic therapy potential unconsidered
      regarding to dermatological indication up to now.

PMID- 11291578
TI  - [Genetic structure of geographically different populations of candida albicans].
AB  - Codominant single-locus markers were developed by amplifying genomic DNA of C.
      albicans with pairs of random primers. Monomorphic PCR products were screened for
      polymorphisms by the SSCP technique. Sequencing confirmed that SSCP's were mostly
      due to single nucleotide substitutions in the polymorphic fragments. A total of
      85 polymorphic loci were observed within 13 PCR fragments. Populations from
      Africa displayed less genotype variation than the populations from Europe and
      USA. Two genetically similar African C. albicans populations exhibiting an
      atypical biotype were strictly clonal and perhaps represent a geographically
      distributed clone. Analyses of "typical" C. albicans populations of different
      geographical origin provided however evidence for both clonality and
      recombination. Evidence for clonality was supported by the absence of segregation
      genotypes, and by deviation of genotypic frequencies from Hardy-Weinberg
      expectations. Tests for nonrandom association of alleles across loci revealed
      less evidence for linkage disequilibrium than expected for strictly clonal
      populations. Although all C. albicans populations tested were primarily clonal,
      evidence for recombination suggests that sexual reproduction or some other form
      of genetic exchange occurs in this species.

PMID- 11291579
TI  - [Candida antigen and antibody kinetics during antifungal therapy in non
      neutropenic intensive care patients].
AB  - The present study aimed at determining Candida antigen and antibody kinetics
      during antifungal therapy. 115 non-neutropenic patients with a stay of more than
      5 days in an interdisciplinary intensive care unit during a period of 2 years
      were reviewed. Routinely measured Candida antigen and antibody titers were
      evaluated at the beginning and during antifungal therapy. In 67 patients
      serological data were evaluable in defined time slots. Under fluconazole therapy
      (FT) the median of Candida antigen (Ramco) was 1:4 and did not change
      significantly. Candida antibody level increased from 1:80 to 1:320. Initial
      titers between FT and amphotericin B/5-fluorocytosine therapy (AT) showed a
      significant difference. During AT antigen titers decreased from 1:8 to 1:4 while
      antibody titers kept constant at a level of 1:160.

PMID- 11291580
TI  - [Results of the first dermatomycoses quality control study in Germany].
AB  - For the first time in the history of German mycology, a multicenter study for
      identification of dermatophytes, yeasts and molds was conducted under the
      auspices of the German Speaking Mycological Society and the German Dermatological
      Society. A total of 1,008 dermatological offices and dermatology hospitals as
      well as 106 institutes of microbiology participated in this voluntary quality
      control trial. They were requested to identify four pathogens: Trichophyton
      tonsurans, Trichophyton mentagrophytes, Aspergillus niger, and Candida glabrata.
      T. tonsurans was correctly determined by 749 participants (67.2%), T.
      mentagrophytes by 974 (87.4%), A. niger by 922 (82.8%) and C. glabrata by 973
      (87.3%). Four pathogens were identified at the species level by 591 investigators
      (53.1%). Three species were correctly identified by 310 investigators (27.8%),
      two by 143 (12.8%) and 0-1 by 70 (6.3%). The first dermatomycological quality
      control study in Germany may therefore be considered a success. Further trials
      will be carried out, initially at intervals of one year.

PMID- 11291581
TI  - Organization development strategies for continuing medical education.
AB  - BACKGROUND: The purpose of this study was to identify organizational strategies
      for improving staff performance in primary care practices. The study rationale
      was based on theory, research, and practice regarding educational interventions
      that help people help themselves. Analysis of qualitative and quantitative data
      produced both plausible explanations of organizational change and implications
      for future efforts. METHODS: The Health Education and Research Trial (HEART)
      Project was an experimental study designed to improve prevention services for
      cardiovascular disease. Primary care clinics were randomized into four
      experimental treatments. Two representative practices from each treatment arm
      were chosen for an in-depth cross-case analysis. Extensive data from each
      selected practice included patient medical record reviews and questionnaires,
      interviews and questionnaires from physicians and clinic staff, project records,
      and follow-up interviews. After detailed case descriptions were created for each
      practice, a cross-case analysis was performed. RESULTS: Each practice improved
      cardiovascular prevention services somewhat. However, there was a great range of
      impact, likely reflecting both experimental intervention and local contingencies.
      Eight positive influences were identified: effective leadership, priority
      setting, joint planning, cooperation and teamwork, acquisition of resources,
      increased support and ownership, accomplishment of improvements, and personal
      changes. Major influences that hindered improvement included patient load,
      turmoil related to reorganization, lack of wide-spread routines, hospital
      affiliated practice, poor communication, and fragmentation within a clinic.
      FINDINGS: Continuing medical education providers can enhance preventive services
      to improve patient health status by promoting organizational change. Suggested
      strategies supported by this study include selecting able leaders, focusing on
      accomplishments, obtaining agreement on prevention priorities, addressing local
      contingencies, increasing teamwork, engaging in joint planning, emphasizing
      quality improvement, acquiring resources, encouraging persistence, and reducing
      hindrances.

PMID- 11291582
TI  - Lifelong learning in ethical practice: a challenge for continuing medical
      education.
AB  - BACKGROUND: Formal education in the identification, analysis, and resolution of
      ethical issues in clinical practice is now an essential component of
      undergraduate and postgraduate medical education. Physicians educated before the
      1980s have had little or no formal education in ethics. This article describes a
      project for assessing the content and format appropriate for the continuing
      education needs of practicing physicians. METHODS: A questionnaire and follow-up
      facilitated small-group discussions with a physician ethicist around case-based
      problems were used to identify the ethical issues in practice where participants
      felt the need for continuing education. RESULTS: The project confirmed that
      practitioners had very little formal ethics in medical school and less since
      starting practice despite encountering ethical issues. The most frequently used
      method of learning about ethics was informal discussion among those who have the
      same lack of formal education. Physicians did not feel that they needed a "very
      high" level of confidence and competence in handling ethical issues, even those
      commonly encountered. Participants indicated strongly that they lacked a
      systematic approach to the identification and analysis of ethical issues and
      suggest incorporation of the ethical component into regular CME. FINDINGS: In
      spite of the small study population and the volunteer nature of the participants,
      the project demonstrated the identification of ethics content for CME similar to
      that used in medical education. Further work is needed to assess objective needs
      for ethics education in addition to the perceived needs of clinicians.

PMID- 11291583
TI  - Follow-up in train-the-trainer continuing medical education events.
AB  - BACKGROUND: The purpose of train-the-trainer (TTT) programs within the context of
      continuing medical education (CME) is to help facilitators acquire and/or enhance
      their skills at leading CME sessions. The provision of follow-up is one feature
      of successful CME workshops over which CME providers have some control. Follow-up
      is defined as any encounter between participants and workshop leaders, following
      an initial workshop or other development session, and is designed to enhance,
      maintain, reinforce, transfer, extend, or support the learning from the original
      workshop. In this article, we elaborate on the use of audio teleconferences to
      provide follow-up for a TTT workshop in Saskatchewan, a largely rural province in
      western Canada. METHODS: The teleconferences began 6 weeks after the workshop and
      were held at approximately 6-week intervals, with five conference calls in total.
      Each lasted about 45 minutes. Participants were interviewed to determine their
      view of the value of the teleconferences. RESULTS: Participants reported learning
      from the teleconferences and feeling more prepared to conduct CME sessions due to
      their participation in the teleconferences. Participants missed teleconferences
      only for extenuating circumstances (e.g., emergency deliveries). FINDINGS: We
      have found that audio teleconferences allow for and encourage professional
      discussion that is crucial to changing practices. They are an effective way to
      incorporate follow-up to TTT workshops when participants travel great distances
      to attend.

PMID- 11291584
TI  - Journal article content as a predictor of commitment to change among continuing
      medical education respondents.
AB  - BACKGROUND: Journal reading is a time-tested means of continuing medical
      education (CME) among physicians. Asking physicians to make a written statement
      of commitment to change has been shown to increase the likelihood of eventual
      change in practice behavior when used in conjunction with CME lectures. We
      describe the type and medical content of articles responsible for commitment to
      change comments among readers of a large circulation primary care journal.
      METHODS: Response to the question "what change(s) do you plan to make in your
      practice as a result of reading the articles in this issue?" were analyzed from
      CME response cards associated with six issues (1 year's publication) of the
      Archives of Family Medicine. Responses indicating a commitment to change were
      analyzed to characterize the type and content of articles responsible for their
      generation. RESULTS: During the 1-year study period, original contributions
      (reports of research trials) dealing with medicine and preventive medicine
      content accounted for the greatest number of comments. After adjusting for the
      frequency of article type and content, special articles and those dealing with
      complementary medicine accounted for the highest number of comments on a per
      article basis. FINDINGS: Family physicians make commitment to change statements
      on the basis of a broad range of journal articles. Certain articles are more
      likely to generate statements of commitment to planned changes in practice.

PMID- 11291585
TI  - Continuing medical education: the paradigm is changing.
AB  - With the realization that lifelong learning is more than attending conferences,
      the potential for greatly expanding effective continuing medical education (CME)
      has never been more encouraging. Databases from groups and individual managed
      care practices and advances in information technology are providing major
      opportunities toward this goal by identifying specific information deficits and
      promoting practice-linked education. The National Committee for Quality Assurance
      (NCQA) standards, requiring audited Health Plan Employer Data and Information Set
      (HEDIS) reports, are a step forward in the development of CME linked closely to
      practice. The optimal educational use of practice data to improve clinical
      outcomes will require research to determine the best methods. HEDIS standards
      will probably continue to deal with common problems of omission rather than with
      those caused by physicians' lack of knowledge, which will require other
      approaches. Development of these methods will provide rich opportunities for
      demonstration studies. The spectacular advances in information technology,
      especially the almost limitless capabilities of the Internet and electronic mail,
      offer boundless possibilities of information sources and enhanced communication
      among physicians about puzzling patients. The further implementation of the
      electronic medical record with computerized reminders and other clinical
      information delivered at the point of need will trigger major advances. An
      appealing user-friendly, practice-linked, and self-directed CME is on the
      horizon, promising to help the practicing physician optimize patient care.

PMID- 11291587
TI  - Getting evidence into practice: the work of the Cochrane Effective Practice and
      Organization of care Group (EPOC).
AB  - Policy makers and continuing educators often face difficult decisions about which
      educational and quality assurance interventions to provide. Where possible, such
      decisions are best informed by rigorous evidence, such as that provided by
      systematic reviews. The Cochrane Collaboration is an international organization
      that aims to help people make well-informed decisions about health care by
      preparing, maintaining, and ensuring the accessibility of systematic reviews of
      the benefits and risks of health care interventions. International collaborative
      review groups prepare Cochrane reviews for publication in The Cochrane Library, a
      collection of databases available on CD-ROM and the World Wide Web and updated
      quarterly. The Cochrane Effective Practice and Organization of Care Group (EPOC)
      aims to prepare and maintain systematic reviews of professional, financial,
      organizational, and regulatory interventions that are designed to improve
      professional practice and the delivery of effective health services. EPOC has 17
      reviews and 20 protocols published in Issue 3, 2000, of the Cochrane Library,
      with further protocols in development. We also have undertaken an overview of
      previously published systematic reviews of professional behavior change
      strategies. Our specialized register contains details of over 1,800 studies that
      fall within the group's scope. Systematic reviews provide a valuable source of
      information for policy makers and educators involved in planning continuing
      education and quality assurance initiatives and organizational change. EPOC will
      attempt to keep the Journal of Continuing Education in the Health Professions
      informed on an ongoing basis about new systematic reviews that it produces in the
      area of continuing medical education and quality assurance.

PMID- 11291588
TI  - Continuing medical education, needs assessment, and program development:
      theoretical constructs.
AB  - Continuing medical education (CME) program development and needs assessment have
      historically been practiced within the tradition of Ralph Tyler's education
      model. In light of transformational social, political, economic, and technical
      forces that demand greater account-ability and responsiveness from physicians,
      CME units are challenged to transform their cultures and structures from models
      that deliver education to models that support the facilitation of learning for
      enhanced competence and performance. This article describes key change forces for
      physicians and brings program development and needs assessment into focus for the
      discussion. The impact of change forces on program development and needs
      assessment are examined, and some techniques to move beyond the traditional
      approach of felt needs are presented as a way of enabling strategic
      administrative planning and change management.

PMID- 11291590
TI  - Dual involvement of coenzyme Q10 in redox signaling and inhibition of death
      signaling in the rat heart mitochondria.
AB  - Coenzyme Q10 (CoQ) has long been utilized as a cardioprotective agent in various
      heart diseases. One of the most important mechanisms by which CoQ exerts
      cardioprotection is aerobic ATP production as a mobile electron carrier in the
      mitochondrial electron transfer chain. The ability of CoQ to afford myocardial
      protection is also attributed to its antioxidant property. However, CoQ may also
      act as a pro-oxidant through the generation of reactive oxygen species. Although
      excess oxidative stress is known to induce death signaling via cytochrome c
      release from mitochondria, it is now apparent that a brief exposure to oxidative
      stress stimulates redox signaling for acquisition of tolerance to oxidative
      stress. Therefore, we have investigated dual involvement of CoQ in redox
      signaling generation through enhanced production of reactive oxygen species and
      death signaling inhibition through antioxidation. Mitochondria were isolated from
      the rat heart and incubated with CoQ (10 or 100 microM) or its vehicle HCO 60 for
      1 h. H2O2 and cytochrome c release from respiring mitochondria were increased by
      antimycin A (2 microM), an inhibitor of complex III respiratory chain, or by high
      Ca2+ (10 microM). This enhanced release of H2O2 was associated with an increase
      in lipid peroxidation as measured with 4-hydroxy-2-nonenal-modified proteins and
      with large amplitude swelling of mitochondria. CoQ potentiated H2O2 release from
      antimycin A- or high Ca(2+)-treated mitochondria, but was capable of inhibiting
      lipid peroxidation and large amplitude swelling, and attenuated cytochrome c
      release from the mitochondria. In addition, CoQ increased ATP synthesis by
      mitochondria. These results suggest that CoQ plays dual roles in mitochondrial
      generation of intracellular signaling. CoQ acts as a pro-oxidant that
      participates in redox signaling. CoQ also acts as an antioxidant that inhibits
      permeability transition and cytochrome c release, and increases ATP synthesis,
      thereby attenuating death signaling toward apoptosis and necrosis.

PMID- 11291591
TI  - Regulation of ventricular fibrillation by heme oxygenase in ischemic/reperfused
      hearts.
AB  - We have assessed the relationship between reperfusion-induced ventricular
      fibrillation (VF) and heme oxygenase (HO) mRNA expression using northern
      blotting, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme
      activity in isolated working ischemic/reperfused rat hearts. Isolated hearts were
      subjected to 30 min of global ischemia followed by 120 min of reperfusion. Upon
      reperfusion with VF, cardiac function was registered (n = 6 in each group), and
      HO mRNAs and enzyme activities were measured at the end of reperfusion in hearts
      that showed VF or did not develop VF. The expression of HO-1 mRNA (about
      fourfold) was observed in ischemic/reperfused nonfibrillated myocardium in
      comparison with the nonischemic control hearts. In those hearts when VF was
      developed, the expression of HO-1 mRNA was not observed in comparison with the
      nonischemic control myocardium. The results measured by RT-PCR and enzyme
      analysis support the data obtained by northern blotting. In additional studies,
      we decided to approach the question from a different angle. Thus, the purpose of
      our work was also to study the role of HO expression and enzyme activity in
      electrically fibrillated hearts without the ischemic/reperfused protocol. To
      simulate the period of 10 min of reperfusion-induced VF, hearts were electrically
      fibrillated, then defibrillated, and perfused for an additional 110 min, and HO-1
      mRNA expression and enzyme activities were determined. Thus, electrically induced
      VF resulted in about 60%, 60%, and 70% reduction in HO-1 mRNA expression, RT-PCR
      signal intensity, and enzyme activity, respectively, compared with the
      nonfibrillated ischemic/reperfused group. In conclusion, our data provide
      evidence that the development of reperfusion-induced VF inhibits HO-1 mRNA
      expression and enzyme activity in both electrically fibrillated myocardium and
      ischemic/reperfused fibrillated hearts. The results clearly show that HO-1 mRNA
      expression and enzyme activity were increased in ischemic/reperfused
      nonfibrillated myocardium, suggesting that interventions that are able to
      increase HO-1 mRNA expression and enzyme activity may prevent the development of
      VF.

PMID- 11291592
TI  - Apoptosis in adriamycin cardiomyopathy and its modulation by probucol.
AB  - The dose-dependent cardiomyopathy and heart failure due to adriamycin have been
      shown to be due to increased oxidative stress and loss of myocytes. We examined
      the incidence of myocardial apoptosis as well as changes in the expression of
      apoptotic regulatory gene products in an established animal model of adriamycin
      cardiomyopathy. Rats were treated with adriamycin (cumulative dose, 15 mg/kg),
      and the hearts were examined for apoptosis as well as expression of Bax, caspase
      3, and Bcl-2 at 0, 4, 10, 16, and 21 days after the treatment. A significant
      increase in the incidence of apoptosis was seen at 4 days, followed by a decline
      at 10 and 16 days of posttreatment. At 21 days, the number of apoptotic cells
      increased again and included cells of the conducting system. Expression of Bax
      corresponded to these biphasic changes, whereas the converse was true for the
      expression of Bcl-2. The latter peaked at 10 days followed by a decline at 16 and
      21 days. The Bax/Bcl-2 ratio also correlated with the incidence of apoptosis.
      Expression of caspase 3 correlated with increased apoptosis, but only at early
      time points. Probucol (cumulative dose, 120 mg/kg), a known antioxidant as well
      as promoter of endogenous antioxidants, significantly reduced the incidence of
      apoptosis as well as expression of Bax. Adriamycin-induced hemodynamic changes
      were also prevented by probucol. These data suggest that adriamycin-induced
      apoptosis is mediated by oxidative stress and may play a role in the development
      of heart failure.

PMID- 11291593
TI  - Characterization of aging-associated up-regulation of constitutive nuclear factor
      kappa B binding activity.
AB  - Changes occur in gene expression during aging in vivo and in replicative
      senescence in vitro, suggesting that aging can affect gene regulation. We have
      recently observed age-related changes in ubiquitously expressed, oxidative stress
      responsive nuclear factor-kappa B (NF-kappa B) pathway during aging. Here we
      report a significant age-related increase in nuclear NF-kappa B binding activity
      together with increased protein levels of p52 and p65 components in rat liver. An
      additional, higher molecular weight protein band seen in their western blots
      suggests that their post-translational modification (but not phosphorylation)
      occurs in liver, which might affect their nuclear localization and binding
      activity during aging. However, aging did not affect the protein levels of the
      main I kappa B inhibitors (I kappa B alpha and I kappa B beta) or I kappa B
      kinase (IKK)-complex subunits (IKK alpha, -beta, and -gamma) involved in NF-kappa
      B activation. In addition, the level of Ser32-phosphorylated I kappa B alpha was
      unaffected by age, suggesting that neither the IKK complex nor altered level of
      the main inhibitors is involved in the observed up-regulation of NF-kappa B
      binding activity. Furthermore, the expression of NF-kappa B mRNAs (p50, p52, p65,
      and c-rel) and the mRNAs of their inhibitors (I kappa B alpha and I kappa B beta)
      did not show any statistically significant age-related changes. These results
      indicate that the expression level of NF-kappa B genes is not significantly
      affected by aging. The up-regulation of constitutive nuclear NF-kappa B binding
      activity and increased levels of nuclear p52 and p65 proteins might affect the
      expression of some NF-kappa B target genes in the aging liver.

PMID- 11291594
TI  - The in vitro cytotoxicity of ascorbate depends on the culture medium used to
      perform the assay and involves hydrogen peroxide.
AB  - Reports about the effects of ascorbate (vitamin C) on cultured cells are
      confusing and conflicting. Some authors show inhibition of cell death by
      ascorbate, whereas others demonstrate that ascorbate is cytotoxic. In this
      report, using three different cell types and two different culture media
      (Dulbecco's modified Eagle's medium and RPMI 1640), we show that the toxicity of
      ascorbate is due to ascorbate-mediated production of H2O2, to an extent that
      varies with the medium used to culture the cells. For example, 1 mM ascorbate
      generates 161 +/- 39 microM H2O2 in Dulbecco's modified Eagle's medium and
      induces apoptosis in 50% of HL60 cells, whereas in RPMI 1640 only 83 +/- 17
      microM H2O2 is produced and no apoptosis is detected. Apoptosis is prevented by
      catalase, and direct addition of H2O2 at the above concentration to the cells has
      similar effects to ascorbate. These results show that ascorbate itself is not
      toxic to the cell lines used and that effects of ascorbate in vivo cannot be
      predicted from studies on cultured cells. The ability of ascorbate to interact
      with different cell culture media to produce H2O2 at different rates could
      account for many or all of the conflicting results obtained using ascorbate in
      cultured cell assays.

PMID- 11291595
TI  - Inhibition of peroxynitrite-induced dityrosine formation with oxidized and
      reduced thiols, nitric oxide donors, and purine derivatives.
AB  - Peroxynitrite, formed by the combination of superoxide anion and nitric oxide, is
      a powerful oxidant at physiological pH and is apparently involved in the
      pathogenesis of several human diseases. Therefore, inhibitors of peroxynitrite
      induced oxidation are important targets for pharmaceutical development. The
      reaction of peroxynitrite with L-tyrosine, one of its biological targets, yields
      stable products, including nitrotyrosine and dityrosine. Here we test the ability
      of thiols, nitric oxide donors, and purine derivatives to inhibit peroxynitrite
      induced dityrosine formation in a physiological buffer containing
      bicarbonate/CO2. We show that both reduced and oxidized thiols, nitric oxide
      donors, and urate, but not other purine derivatives, reduce peroxynitrite-induced
      dityrosine formation.

PMID- 11291596
TI  - Redox regulation of cardiomyocyte survival and death.
AB  - In this review, attempts were made to establish the role of reactive oxygen
      species as signaling molecules that regulate cardiomyocyte life and death during
      ischemia and reperfusion. Ischemia/reperfusion is a classical example because
      partial or mild ischemia can lead to simultaneous execution and repair of the
      cardiomyocytes, which is disrupted during severe ischemia leading to cell
      necrosis because of the lack of ATP. Apoptosis and repair processes are mediated
      by adaptive response in which oxygen free radicals function as typical signaling
      molecules through the activation of receptor tyrosine kinases, protein kinase C,
      and mitogen-activated protein kinases, as well as induction of redox-sensitive
      transcription factors and genes.

PMID- 11291597
TI  - Role of oxidants in the signaling pathway of preconditioning.
AB  - This review focuses on the possible role of reactive oxygen species in the
      pathogenesis of this phenomenon. Evidence in support of a role of oxidants in
      preconditioning has come from the observation that administration of oxygen
      radical scavengers during the reperfusion period following the initial
      "preconditioning" ischemia could prevent the phenomenon. In addition, a brief
      exposure to a low, nontoxic dose of oxygen radicals may reproduce the beneficial
      effects of ischemic preconditioning, thus suggesting that radicals can directly
      trigger the preconditioning pathway. To explain the effects of oxidants in this
      setting, it has been suggested that reperfusion after the initial,
      "preconditioning" ischemic episode results in the generation of relatively low
      amounts of oxygen radicals, which are insufficient to determine cell necrosis,
      but nevertheless could modify cellular activities that have been implicated as
      mediators of the preconditioning phenomenon. Recent evidence suggests that low
      levels of oxidants may have a modulatory role on several cell functions. Possible
      mechanisms of oxidant-mediated protection might be protein kinase C and other
      kinases, ATP-dependent potassium channels, or changes in sulfhydryl group redox
      state, while an effect on adenosine metabolism, or the induction of myocardial
      stunning presumably does not contribute to oxidant-mediated preconditioning.
      Finally, de novo protein synthesis and gene expression, and increased antioxidant
      defenses might be involved in the late phase of preconditioning. In summary,
      available data strongly suggest that oxygen radicals might be possible mediators
      of preconditioning. However, further investigation is required to clearly
      elucidate their exact role and mechanisms of action.

PMID- 11291598
TI  - Delivery of antioxidant enzyme proteins to the lung.
AB  - Protection of alveolar epithelial cells (alveolocytes) and vascular endothelial
      cells against pulmonary oxidative stress is an important problem. An inadequate
      delivery to the target cells limits the protective utility of the antioxidant
      enzymes, superoxide dismutase (SOD) and catalase. SOD and catalase modifications,
      such as coupling with polyethylene glycol and encapsulation in liposomes, prolong
      the life span of the active enzymes in vivo. The airway administration of SOD and
      catalase protects alveolocytes against hyperoxic oxidative stress. Although
      pulmonary endothelium is poorly accessible from the airways, it is accessible
      from circulation. However, antioxidant enzymes and their derivatives display poor
      targeting to pulmonary endothelium. To improve the targeting and provide
      intracellular delivery to endothelium, the enzymes can be conjugated with
      antibodies against endothelial antigens, such as angiotensin-converting enzyme
      and adhesion molecules [intercellular adhesion molecule-1 (ICAM-1) or platelet
      endothelial cell adhesion molecule-1 (PECAM-1)]. These immunoconjugates
      accumulate in the pulmonary vasculature in intact animals, enter endothelium, and
      augment the antioxidant defenses. The immunoconjugates directed against ICAM-1
      and PECAM-1 may also provide a secondary therapeutic benefit by blocking of
      sequestration and infiltration of leukocytes in the lungs. Further investigations
      are necessary to evaluate the therapeutic effectiveness of the vascular
      immunotargeting of antioxidant enzymes and solve technical problems associated
      with production of safe, clinically useful conjugates.

PMID- 11291599
TI  - Cardiac toxicity of singlet oxygen: implication in reperfusion injury.
AB  - Oxygen-derived free radicals (O2.-, H2O2, and .OH) that are produced during
      postischemic reperfusion are currently suspected to be involved in the
      pathogenesis of tissue injury. Another reactive oxygen species, the
      electronically excited molecular oxygen (1O2), is of increasing interest in the
      area of experimental research in cardiology. In this review are discussed the
      main potential sources of singlet oxygen in the organism, particularly in the
      myocardium, the various cardiovascular cytotoxic effects induced by this reactive
      oxygen intermediate, and the growing evidence of its involvement in
      ischemia/reperfusion injury.

PMID- 11291600
TI  - Fatty acid-induced apoptosis in neonatal cardiomyocytes: redox signaling.
AB  - Exposure of neonatal rat cardiac myocytes to palmitate and glucose produces
      apoptosis as seen by cytochrome c release, caspase 3-like activation, DNA
      laddering, and poly(ADP-ribose) polymerase cleavage. The purpose of this study
      was to understand the role of reactive oxygen species in the initiation of
      programmed cell death by palmitate. We found that palmitate (but not oleate)
      produces inhibition of carnitine palmitoyltransferase I, accumulation of
      ceramide, and inhibition of electron transport complex III. These events are
      subsequent to cytochrome c release and loss of the mitochondrial membrane
      potential. No differences in H2O2 production or N-terminal c-Jun kinase
      phosphorylation were detected between myocytes incubated in palmitate and control
      myocytes (nonapoptotic) incubated in oleate. These results suggest that the
      palmitate-induced loss of the mitochondrial membrane potential is not associated
      with H2O2 synthesis and that a membrane potential is required to generate
      reactive oxygen species following ceramide inhibition of complex III.

PMID- 11291601
TI  - Antioxidant treatment inhibits activation of myocardial nuclear factor kappa B
      and inhibits nitrosylation of myocardial heme protein in cardiac transplant
      rejection.
AB  - Nitric oxide production via inducible nitric oxide synthase (iNOS) is believed to
      play a role in cardiac allograft rejection. Previously, we showed that
      antioxidants can significantly prolong cardiac graft survival, but the nature of
      this protection is unknown. In the present study, we examined the protective
      effect of another antioxidant, dimethylthiourea (DMTU), in a model of cardiac
      allograft rejection. Specifically, we hypothesized that DMTU would prolong graft
      survival and decrease activation of nuclear factor-kappa B (NF-kappa B), an
      important redox-sensitive transcription factor necessary for iNOS gene
      expression. NF-kappa B was activated by twofold as early as postoperative day 2
      in allografts. NF-kappa B activation in allografts progressed to a peak of
      ninefold by postoperative day and remained increased until postoperative day 6.
      No activation of NF-kappa B was observed in isografts for comparable time
      periods. Treatment with DMTU resulted in a significant prolongation of graft
      survival. This beneficial effect was associated with diminished activation of
      myocardial NF-kappa B. Treatment with DMTU also resulted in decreased formation
      of iron-nitrosylprotein complexes as evidenced by electron paramagnetic resonance
      spectroscopy. These studies provide evidence that reactive oxygen plays a
      significant role in signal transduction for activation via the transcription
      factor, NF-kappa B, thereby modulating distal actions and consequences of iNOS
      derived nitric oxide.

PMID- 11291602
TI  - Effects of hypoxia/reoxygenation on angiogenic factors and their tyrosine kinase
      receptors in the rat myocardium.
AB  - The process of angiogenesis is initiated primarily as a consequence of hypoxic
      stimulation at the cellular and molecular level. Although several angiogenic
      growth factors have been identified, at present a detailed understanding of the
      interplay among inducing stimuli, growth factors, and their respective molecular
      targets remains to be evaluated. Here we report the effects of progressively
      increasing durations of moderate hypoxia on the protein expression profiles and
      tissue distribution patterns of the vascular endothelial growth factor system and
      the angiopoietin/Tie system in the adult rat myocardium. The relative temporal
      trends of expression of the various components of these two systems, as well as
      apparent relationships between Flk-1 and angiopoietin-2 and between Flt-1 and Tie
      1, suggest a probable sequence of involvement during myocardial angiogenesis, as
      proposed in our model. Such relationships may potentially be utilized in
      formulating strategies for sequential gene therapy to achieve clinically relevant
      myocardial angiogenesis.

PMID- 11291603
TI  - [Diagnosis of diabetic autonomic neuropathy in young patients with diabetes
      mellitus type 1].
AB  - Autonomic neuropathy, particularly cardiovascular autonomic neuropathy (CAN) is
      one of the complications of the diabetes mellitus both types. It leads to life
      comfort's declination but may also be the direct cause of death in diabetes
      mellitus patients. It seems that degree of metabolic control and duration of the
      disease is connected with prevalence and severity of CAN. The aim of our study
      was to assess cardiac autonomic function in young subjects suffered from insulin
      dependent diabetes mellitus (IDDM) with relatively short duration time of the
      disease. We subdivided 25 (m-12, f-13) IDDM patients aged from 18 to 30 years:
      mean--26 +/- 38 years, with duration time of the disease up to 10 years,
      normotensive and without nephropathy and retinopathy. We created 25 healthy
      volunteers control group with similar age and sex. In all selected subjects full
      Ewing's battery tests were performed as well as the spectral analysis of power
      heart rate variability (HRV) was assessed with Finapress device (Ohmeda 2300) and
      automatically computed with special software. HRV in total spectrum power TP from
      0.001-0.5 Hz, high frequency (HF) band from 0.15-0.3 Hz, low frequency (LF) band
      from 0.03-0.15 Hz and LF/HF ratio were examined both in supine and tilt. All
      assessed spectral values were significantly lower in IDDM patients then these in
      controls whereas LF/HF were respectively higher. Valsalva tests and deep
      breathing HR response tests were significantly differed among groups but within
      normal limits. We concluded that when spectral analyse was performed, in young
      IDDM patients with short duration time of the disease, impairment of cardiac
      autonomic function was observed.

PMID- 11291604
TI  - [Serologic and cytochemical examinations for surveillance of cytomegalovirus
      infection and reactivation after hematopoietic cell transplantation].
AB  - 208 patients and 1327 blood/platelet donors were monitored for the presence of
      CMV antibodies. Serological tests were used for the detection of IgM and IgG CMV
      antibodies and cytochemistry (APAAP) for CMV antigens detection. RESULTS: 1) In
      haematological patients and in blood/platelet donors proportions of IgG CMV
      antibodies were similar (about 75%). 2) The presence of IgM-CMV antibodies was
      significantly more frequent in patients than in donors group (4/208 vs 4/1327, p
      = 0.0025). 3) CMV early and immediate early antigens (p52, Ad169) were detected
      in 31 patients. CMV antigenemia occurred in 11/31 patients and were found between
      13 and 78 days after BMT. In 11 patients a number of CMV + cells ranged from 12
      to 11,500/10(5) (median values 25 positive cells/10(5)). Patients receiving anti
      thymocyte serum (13/31) were on Ganciclovir pre-emptive treatment. CMV
      antigenemia positive patients were in similar proportions in the groups receiving
      and lacking ATG (ATG is a risk factor of CMV reactivation) as a part of
      conditioning regimen. In addition median value of CMV positive leukocytes was
      lower in ATG receiving patients than patients lacking ATG. This was likely due to
      the effective Ganciclovir pre-emptive treatment offered to all patients on ATG.

PMID- 11291605
TI  - [Evaluation of complement component C4 concentration and immunoglobulins IgA,
      IgG, and IgM in serum of patients with primary essential hypertension].
AB  - The aim of the study was to determine serum concentration of complement component
      C4 and IgA, IgG, IgM immunoglobulins in hypertensive patients and healthy
      controls as well as to assess the interrelationships regarding some immunological
      and clinical data in the study group. The study group consisted of 81
      hypertensive patients (with secondary forms of hypertension excluded), 44 females
      and 37 males (mean age 51.2 +/- 14.5 years). The control group comprised 34
      healthy volunteers, 19 females and 15 males (mean age 47.5 +/- 15.3 years). C4,
      IgA, IgG, IgM serum concentrations were evaluated with turbidymetry. C4 serum
      concentration was significantly higher in hypertensive patients when compared to
      the controls. No significant differences in IgA, IgG, IgM serum concentrations
      existed between the groups. The duration of hypertension correlated positively
      with C4 serum concentration. Elevated C4 serum concentration may be one of the
      markers of immunological disturbances existing in hypertensive patients. IgA,
      IgG, IgM immunoglobulins do not seem to be directly associated with essential
      hypertension.

PMID- 11291606
TI  - [Blood gas analysis of forearm veins--at rest and after exercise of forearm
      muscles and laser Doppler flowmetry of skin on the back of the palm--use in
      evaluation of microcirculation in diabetes type 2].
AB  - The aim of the study was to compare of nondominant forearm microcirculation in
      adult-type diabetes and healthy subjects with use of venous blood gasometry (vbg)
      sampled from basilic vein before and after exercise of antebrachial muscles and
      with use of laser doppler fluxometry (LDF) with optode localized in dorsal palm
      surface. Examinations were performed in groups of 16 diabetic patients (aged 43.5
      +/- 5.7) and 16 healthy subjects (aged 39.3 +/- 7.8). After exercise of
      antebrachial muscles in diabetic patients in vbg were: pH higher, pO2 and satO2
      lower than in healthy subjects, pCO2 and -HCO3 were not different in both group.
      In LDF in diabetic patients impaired hypraemic reaction, impaired heating to 40
      degrees C reaction and hyperaemic reaction in this temperature were found.

PMID- 11291607
TI  - [Sex steroids versus lipid profile and the degree of coronary artery stenosis in
      men with angiographically documented coronary artery disease].
AB  - The aim of the study was to assess the correlations between the levels of sex
      hormones and blood lipid profile as well as indexes of coronary artery stenosis
      in men with angiographically documented coronary artery disease. 111 men, aged 36
      73 yrs (av. 55) were studied. In all the patients levels of testosterone (T),
      dehydroepiandrosterone sulfate (DHEA-S), estradiol (E), SHBG, LH and FSH were
      measured. The level of bioavailable testosterone (BT) was calculated knowing SHBG
      level. Total cholesterol (TCh), HDL-cholesterol, LDL-cholesterol and
      triglycerides (TG) levels were estimated as well as the degree of coronary artery
      stenosis was estimated by means of modified indexes. For statistics R-Spearman
      test was used. Summing coronary stenosis index correlated significantly with T-Ch
      and LDL-Ch levels. Positive correlation was found between blood level of E and
      TCh as well as between E and LDL-Ch. BT correlated partially with LDL-Ch level.
      No correlations were found between the levels of T, SHBG, DHEA-S, FSH, LH and
      lipid profile. The level of DHEA-s revealed negative correlation with age, while
      the level of SHBG increased with ageing leading to the decrease of the value of
      BT but not total T. None of studied hormones correlated with coronary indexes.
      Our results suggest that estradiol and BT may promote the formation of
      atherogenic lipid profile leading to atherosclerosis in men.

PMID- 11291608
TI  - [Five year clinical evaluation of treatment efficacy with methotrexate in
      patients with rheumatoid arthritis ].
AB  - The objective of this study was to determine long term efficacy and safety of low
      dose methotrexate (MTX) in treatment of rheumatoid arthritis (RA). Thirty
      patients receiving MTX for RA were prospectively studied over a mean treatment
      period of 60 months. Standard clinical and laboratory measures of disease
      activity were assessed by the same investigator at baseline, and at 3, 6, 24, and
      60 months. The occurrence of adverse reactions was noted. Initially MTX was given
      orally 7.5 mg once a week. In the course of the observation the dose ranged
      between 5 and 15 mg/week. 13 patients (43%) completed 5-years study. Treatment
      with MTX was stopped due to adverse events in 4 cases, inefficacy in 7 patients,
      poor compliance and fear of toxicity in 3 patients and death in 3 patients. The
      factors related to their death were unrelated in all 3 cases to study MTX
      therapy. In 13 patients who completed 60 months of therapy, a significant
      improvement was noted comparing to baseline in 9 out of 12 clinical disease
      variables and acute phase reactants. There was also a significant decrease in the
      mean daily dosage of NSAIDs. Adverse events occurred in 64% of the patients, but
      only 13% of the patients discontinued MTX permanently. The side effects occurred
      more often in older patients. RA patients treated for five years with MTX showed
      statistically significant clinical improvement and decrease of inflammation
      parameters. MTX treatment may be helpful also in patients with advanced forms of
      RA.

PMID- 11291609
TI  - [Disseminated tuberculosis--diagnostic difficulties in a patient with chronic
      heart failure].
AB  - We presented case 64 year old patient with disseminated tuberculosis. The main
      symptom was fever and his death was due to respiratory and circulatory failure.
      In spite of extensive diagnostic research the aetiology of sepsis was not
      identified and the treatment was ineffective. In patients with severe
      disseminated tuberculosis the traditional diagnostic methods are often not
      effective.

PMID- 11291610
TI  - [Use of intravascular ultrasonography (IVUS) for diagnosis and treatment of
      coronary artery disease--case report].
AB  - One of the additional methods of coronary artery assessment is intravascular
      ultrasound (IVUS). Contrary to coronary angiography this relatively new technic
      provides new information including precise calculations of stenosis degree,
      morphology of atheromatous plaque and differentiation of its structure. Coronary
      angiography was performed in 54 years old male patient with unstable angina,
      revealing 99% stenosis in distal RCA. Discrepancy between clinical presentation
      and angiographic findings and exercise test resulted in performing IVUS of LAD.
      Angiographically clear LM and LAD were found to be narrowed 52% and 58% on IVUS.
      Subsequent CABG resulted in symptoms withdrawal and increase of physical
      tolerance. Exercise test after CABG did not reveal ischaemia in area of LCA at 10
      METs. IVUS is found to be an important technic in assessment of silent or
      ambiguous lesions and in many cases allows to choose the optimal method of
      treatment of coronary artery disease.

PMID- 11291611
TI  - [The role of oxygen radicals in Helicobacter pylori infections].

PMID- 11291612
TI  - [Hypertrophy, rebuilding and remodeling of myocardium. Causes, clinical
      significance and therapeutic implications].

PMID- 11291613
TI  - [Diagnosis of autoimmune hepatitis].

PMID- 11291614
TI  - [Polymorphism of the angiotensin converting enzyme gene (ACE) and kidney
      diseases].

PMID- 11291615
TI  - [Giant cell arteritis and rheumatica polymyalgia].

PMID- 11291616
TI  - [Acute respiratory distress syndrome (ARDS)].

PMID- 11291617
TI  - Membrane transport meets plant nutrition.

PMID- 11291618
TI  - Management of dental patients who are HIV positive.

PMID- 11291619
TI  - Proceedings of the 18th Southern Biomedical Engineering Conference and the 2nd
      International Conference on Ethical Issues in Biomedical Engineering. Clemson,
      South Carolina, USA. May 21-23, 1999.

PMID- 11291620
TI  - [IXth Congress on prevention of nosocomial infections. Paris, November 18-19,
      1998. Proceedings].

PMID- 11291621
TI  - Society for the Study of Ingestive Behavior annual meeting. 25-29 July 2000.
      Dublin, Ireland. Abstracts.

PMID- 11291622
TI  - [7th Annual meeting of the CAQ jointly with the Surgical Research Section of the
      German Society of Surgery. Value of clinical studies in the framework of surgical
      quality assurance. Cottbus, 5-6 February 1999. Proceedings].

PMID- 11291623
TI  - Special issue in memory of Dr. Alexander Krayevsky.

PMID- 11291624
TI  - 1st France-Israel Binational Workshop on Biosensors and Biochips. Omer, Israel,
      October 27-28, 1998. Proceedings.

PMID- 11291625
TI  - [Physiopathology in the aged and the countermeasures--characteristics of the
      respiratory physiology in the aged].

PMID- 11291626
TI  - Origins and clinical relevance of sarcopenia.
AB  - Sarcopenia is the loss of muscle mass and strength that occurs with normal aging.
      Because sarcopenia is not the result of a disease, it is seen in all aged adults.
      Sarcopenia markedly increases the risk of disability and loss of functional
      capacity in the elderly. The mechanisms underlying sarcopenia are complex and are
      reviewed here. It is not clear at this time which factors are most important in
      determining the severity or rate of development of sarcopenia. While progressive
      resistance training clearly can reverse and prevent sarcopenia, little is known
      about the mechanisms by which aged muscle adapts to training, or whether these
      adaptations reflect reversal of direct pathophysiological processes or
      compensation by activation of separate pathways from those leading to the
      deterioration in the first place. As populations in developed countries continue
      to age, diagnosing, treating, and preventing sarcopenia will be progressively
      more important to the health and well-being of modern societies.

PMID- 11291627
TI  - Pain relief during labor.

PMID- 11291628
TI  - External cephalic version.

PMID- 11291629
TI  - Dynamics of stab wounds: force required for penetration of various cadaveric
      human tissues.

PMID- 11291630
TI  - Whiplash and symptom amplification.

PMID- 11291631
TI  - Smiling faces as anchor for pain intensity scales.

PMID- 11291632
TI  - Electroconvulsive therapy and pain.

PMID- 11291633
TI  - A case of vaccine-associated paralytic poliomyelitis.

PMID- 11291634
TI  - Mapping addiction.

PMID- 11291635
TI  - Structure and function in comparative physiology: A tribute to Pierre Laurent.
      Proceedings of a meeting. March 25-26, 1996.

PMID- 11291636
TI  - Routine provision of emergency contraception to teens and subsequent condom use:
      a preliminary study.

PMID- 11291637
TI  - Onset of psychosis after cerebellum pathology: a case report.

PMID- 11291638
TI  - Possible genetic link between seasonal affective disorder and eating disorders.

PMID- 11291639
TI  - Measuring care needs and case-mix by means of the INTERMED.

PMID- 11291640
TI  - Dermatologic presentation of panic disorder.

PMID- 11291641
TI  - Response to nefazodone in a depressed patient with end-stage renal disease.

PMID- 11291642
TI  - [Drug-induced aphthae].

PMID- 11291643
TI  - [Reporting drug side effects in dermatology].

PMID- 11291644
TI  - [Continuous or intermittent treatment of psoriasis?].

PMID- 11291645
TI  - [Treatment of superficial leg phlebitis].

PMID- 11291646
TI  - [Treatment of superficial leg phlebitis].

PMID- 11291647
TI  - [Treatment of superficial leg phlebitis].

PMID- 11291648
TI  - Colonic adenocarcinoma in rhesus macaques.
AB  - Colon cancer is the second most common cause of cancer mortality in human beings,
      but relatively few cases have been described in macaques. The present report
      documents two fatal cases of colon cancer in aged rhesus macaques. Case 1 was a
      20-year-old female in which extensive invasion of the caecum by a scirrhous
      adenocarcinoma led to perforation and a severe fibrinopurulent peritonitis. Case
      2 was a 32-year-old male with a stricture at the ileocaecal junction, also caused
      by a scirrhous adenocarcinoma, which had metastasized to a regional lymph node.
      Both neoplasms showed aggressive local involvement of the proximal large bowel,
      which appears to be a predilection site in rhesus monkeys. Descriptions of
      spontaneous cases of colon cancer in non-human primates may lead to the
      development of models for certain aspects of the disease in man.

PMID- 11291649
TI  - Inhibition of NF-kappaB and AP-1 activation by R- and S-flurbiprofen.

PMID- 11291650
TI  - Hospital accreditation is important.

PMID- 11291651
TI  - Insulin-like growth factor-I can be helpful towards end of life.

PMID- 11291652
TI  - Drug development means economics in the end.

PMID- 11291653
TI  - When response rates do matter.

PMID- 11291654
TI  - Census of availability of neonatal intensive care should have used different
      denominator.

PMID- 11291655
TI  - Drugs may have reduced effect of falls intervention.

PMID- 11291656
TI  - Tampons could be used to diagnose sexually transmitted diseases.

PMID- 11291657
TI  - Putting patients first will help interprofessional education.

PMID- 11291658
TI  - Is it time to dismiss calls to ban DDT.

PMID- 11291659
TI  - Proposals for preventing community violence are naive.

PMID- 11291660
TI  - Is this the end of the line for flu vaccine as we know it?

PMID- 11291661
TI  - [BLM (RCQL2) or Bloom Syndrome].

PMID- 11291662
TI  - [Ha-ras, N-ras et Ki-ras].

PMID- 11291666
TI  - Phenylpropanolamine and hemorrhagic stroke.

PMID- 11291667
TI  - Phenylpropanolamine and hemorrhagic stroke.

PMID- 11291668
TI  - Dietary supplements containing ephedra alkaloids.

PMID- 11291669
TI  - Dietary supplements containing ephedra alkaloids.

PMID- 11291670
TI  - The diagnosis and treatment of cough.

PMID- 11291671
TI  - The diagnosis and treatment of cough.

PMID- 11291672
TI  - The diagnosis and treatment of cough.

PMID- 11291673
TI  - Syncope.

PMID- 11291674
TI  - Syncope.

PMID- 11291675
TI  - Invasive pulmonary aspergillosis associated with infliximab therapy.

PMID- 11291676
TI  - [Directive 97/35/CE of the Commission of June 18, 1997. By which the Directive
      90/220/CEE is adapted for the second time to technical progress. Of the Council
      on the intentional release of genetically engineered organisms to the environment
      (Text relevant to the purposes of the EEE)].

PMID- 11291677
TI  - [Laparoscopic posterior fundoplication in gastroesophageal reflux: mid-term
      results].
AB  - STUDY AIM: The aim of this study was to report the mid-term results of the
      surgical management of gastroesophageal reflux disease (GERD) by laparoscopic
      posterior partial fundoplication (Toupet technique) in 100 patients, and to
      evaluate their post-operative quality of life. PATIENTS AND METHOD: Between
      November 1993 and January 2000, 100 patients were surgically treated for a
      medically refractory GERD. Laparoscopic posterior partial fundoplication was
      performed by the Toupet technique. In the postoperative period, the patients were
      asked to answer a questionnaire by telephone. The aim of this survey was three
      fold: to identify clinical symptoms indicative of recurrence; to evaluate
      postoperative functional impairment; to assess the postoperative quality of life.
      pH monitoring was also proposed in asymptomatic patients at a minimum follow-up
      of two years, and in all patients with clinical symptoms of GERD recurrence.
      RESULTS: Six laparotomy conversions were necessary. The mean duration of follow
      up was 18 months (range: 6 to 57 months). The rate of clinically diagnosed
      recurrence was 7.6%. Intermittent dysphagia was observed in 2.3% of cases.
      Postoperative digestive functional disorders were noted in 53% of patients
      without clinical recurrence, and 95.3% of them were satisfied or very satisfied
      with the results of surgery. CONCLUSION: Laparoscopic posterior partial
      fundoplication by the Toupet technique can satisfactorily treat GERD without mid
      term recurrence in about 94% of cases. Patient satisfaction seems mainly to
      depend on the disappearance of clinical symptoms of GERD. It was found that
      postoperative functional disorders frequently occurred, but were well tolerated.
      Their etiology has not yet been determined, and it is considered that factors
      other than the surgical procedure may also play a role.

PMID- 11291678
TI  - [Funeral oration in praise of Auguste Berard given by C.P. Denonvilliers during
      the 20 October 1852 session of the Paris Society of Surgery ].
AB  - In 1843 Auguste Berard created the Societe de chirurgie de Paris which later took
      the name of the Academie de chirurgie dissolved in 1793 by the French Revolution.
      Auguste Berard was forty years old in those days. He had just been appointed
      Professor of clinical surgery and became the first President of the Societe de
      chirurgie de Paris. Three years later, his colleagues were mourning for him.

PMID- 11291679
TI  - On human embryos and medical research: an appeal for ethically responsible
      science and public policy.

PMID- 11291680
TI  - Expression of metallothionein in seminal vesicles--an immunohistochemical study.
AB  - OBJECTIVE: The seminal vesicles and prostate share the same blood supply and
      exposure to carcinogens. Despite these similarities, fewer than 60
      adenocarcinomas of the seminal vesicles have been described, whereas prostate
      cancer is the most common cancer in men today. Metallothionein plays a
      significant role in the detoxification of heavy metals. Thus, this study
      investigated the expression of metallothionein in seminal vesicle tissue.
      MATERIAL AND METHODS: Twenty individual tissue specimens each of normal seminal
      vesicle tissue and benign prostatic tissue underwent immunohistochemical staining
      with a monoclonal mouse anti-metallothionein antibody. RESULTS: Positive
      immunostaining for metallothionein was found in 8 of 20 (40%) of the seminal
      vesicle tissues, but in 14 of 20 (70%) of the prostate specimens. Seminal vesicle
      tissue stained only with weak intensity. CONCLUSION: Metallothionein expression
      is lower in seminal vesicles than in the prostate. The low cell turnover in
      seminal vesicle tissue may explain the lower staining activity of this tissue.
      These findings suggest that metallothionein expression cannot be regarded as the
      main reason for the vastly different cancer incidence in seminal vesicles and the
      prostate.

PMID- 11291681
TI  - p53 expression in correlation to clinical outcome in patients with renal cell
      carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of p53 as prognostic
      factor in renal cell carcinoma (RCC) and its relation to clinicopathological
      factors. MATERIAL AND METHODS: The nuclear accumulation of p53 protein was
      determined by immunohistochemical analysis in RCC specimens from 90 patients and
      was correlated with clinical stage, grade, DNA ploidy, S-phase fraction and
      cancer-specific survival. RESULTS: p53 overexpression was observed in 17 of 90
      (19%) tumours. There was a significant correlation to stage (p = 0.016) and grade
      (p = 0.020) but not to DNA ploidy or S-phase. Patients with high p53
      immunoreactivity had shorter cancer-specific survival (p = 0.003) than those with
      normal p53 protein expression. This difference was found in papillary and
      chromophobe tumour types (p < 0.0001) but not in conventional RCC. CONCLUSIONS:
      In patients with RCC, significant correlations between p53 protein expression and
      tumour stage, grade and survival time were observed. For patients with
      chromophobe and papillary tumour types, but not in conventional RCC, p53
      immunoreactivity gave prognostic information, suggesting that the prognostic
      differences in p53 immunoreactivity might be due to disparate genetic
      abnormalities in the different RCC types.

PMID- 11291682
TI  - Management of testicular cancer--16 years' experience from southwest Finland.
AB  - OBJECTIVE: This study investigated the outcome of testicular cancer treatment in
      Finland. MATERIAL AND METHODS: Data on 88 testicular cancer patients treated in
      Turku University Central Hospital between 1976 and 1992 were studied to analyse
      outcome and survival. RESULTS: The histological diagnosis was seminoma for 39
      patients and non-seminoma for 49 patients. Two seminoma patients relapsed (5%)
      and one patient died of progressive disease (3%; initially stage II seminoma).
      Eleven non-seminoma patients relapsed (22%), nine of whom were cured with
      chemotherapy. Four non-seminoma patients died of progressive disease (8%;
      initially one stage I non-seminoma and three stage III non-seminomas). The median
      time to relapse after the completion of treatment was 9 months (range 3-50
      months). Non-seminoma patients had significantly more relapses than seminoma
      patients (p = 0.03). Most relapses (73% of the non-seminoma relapses) were found
      among the stage I non-seminoma patients who had not received adjuvant
      chemotherapy, while none of the stage I seminoma patients relapsed (p = 0.007).
      CONCLUSIONS: Close surveillance is important for all non-seminoma patients to
      guarantee the early detection and treatment of recurrent disease. Treatment and
      surveillance should be covered by national guidelines and be conducted in centres
      with special interest in this rare but mostly curable cancer.

PMID- 11291683
TI  - A Norwegian national cohort of 3198 women treated with home-managed electrical
      stimulation for urinary incontinence--demography and medical history.
AB  - OBJECTIVE: The aim of this study was to describe the demography, medical history
      and clinical characteristics of women treated with home-managed electrical
      stimulation in Norway. MATERIAL AND METHODS: This prospective cohort study
      investigated all 3198 women treated with home-managed electrical stimulation in
      Norway from 1992 to 1994. Data were collected from both patients and physicians
      by questionnaires before and after treatment. RESULTS: Mean age was 53 years.
      According to the physicians, 43, 15, 37 and 5% of the patients had stress, urge,
      mixed incontinence and other diagnoses, respectively. Fifty-five per cent of the
      women had had symptoms for 5 years or more, 62% had urinary loss every day/night,
      and 59% of the patients were classified as having severe or very severe
      incontinence according to a validated severity index. Fifty-two per cent of the
      women used a long-term stimulator and 48% a maximal stimulator. Of 645 physicians
      who requested stimulators, 65% worked in general practice; 70% of the stimulators
      were requested by physicians working in hospital or specialists in private
      practice. Gynaecologists requested 53% of the stimulators. CONCLUSIONS: The
      Norwegian reimbursement system can be said to be a numeric success. Electrical
      stimulation is a treatment option for everyday use in Norway. This complete
      national cohort of 3198 women treated with home-managed electrical stimulation
      for urinary incontinence was biased towards younger patients and more severe
      incontinence.

PMID- 11291684
TI  - A Norwegian national cohort of 3198 women treated with home-managed electrical
      stimulation for urinary incontinence--effectiveness and treatment results.
AB  - OBJECTIVE: The aim of this study was to analyse the effectiveness of home-managed
      electrical stimulation. MATERIAL AND METHODS: A prospective cohort study was
      conducted on all 3198 women treated with home-managed electrical stimulation in
      Norway during 1992-1994. Data were collected from both patients and physicians by
      questionnaires before and after treatment. RESULTS: 29% of the women were cured
      or much improved according to their own assessment; altogether 61% were improved.
      According to the physicians' assessment, 33% were cured or much improved; a total
      of 55% was improved. Thirty-seven per cent of compliers and 12% of non-compliers
      regarded themselves as cured or much improved. The number of incontinence
      episodes, amount of leakage and use of pads decreased significantly; and 44% had
      less severe incontinence than before treatment according to a validated severity
      index. CONCLUSIONS: Women treated with electrical stimulation for urinary
      incontinence experienced a significant reduction in incontinence problems, both
      subjectively and semi-objectively. The treatment results seem to be strongly
      dependent on good acceptance of the treatment.

PMID- 11291685
TI  - Acupuncture therapy in the management of persistent primary nocturnal enuresis-
      preliminary results.
AB  - OBJECTIVE: This study aimed to assess the comparative therapeutic efficacy of
      traditional Chinese acupuncture. MATERIAL AND METHODS: During the period from
      January 1997 to April 1999, 50 children (23 boys, 17 girls) suffering from
      primary persistent nocturnal enuresis, aged 9-18 years, were included in the
      study. The response rate was monitored at 2 and 4 weeks, and then every 3 months
      by recording dry nights on a calendar. RESULTS: The efficacy of treatment, which
      was expressed as a percentage of dry nights, was high. Within 6 months, 43 (86%)
      patients were completely dry and 2 (10%) patients were dry on at least 80% of
      nights. CONCLUSIONS: Treatment using acupuncture in patients with persistent
      enuresis nocturna appeared to be most efficacious both in terms of the percentage
      of dry nights at the end of treatment and in relation to the stability of
      results, even after the end of the study.

PMID- 11291686
TI  - Treament of nocturnal enuresis.

PMID- 11291687
TI  - Long-term renal dysfunction in patients with acute urinary retention.
AB  - OBJECTIVE: Acute urinary retention (AUR) causes bilateral renal obstruction,
      which has been found to affect kidney function. This study evaluated both
      glomerular and tubular renal function in the long term after the resolution of
      AUR. MATERIAL AND METHODS: Renal function in 15 patients affected by AUR and
      found still to evince renal dysfunction 6 months afterwards was re-evaluated
      approximately 18 months after the episode. The bladder outlet obstruction was
      treated and all patients voided normally at 6 month control. RESULTS: The
      percentage of patients suffering from lowered creatinine clearance and elevated
      alpha1-microglobulin excretion increased during follow-up from AUR up to 6 and 18
      months (46% to 57% to 79% and 42% to 71% to 100%, respectively). In addition,
      daily protein excretion was abnormally high in 69% of patients at the 18 month
      follow-up. In most cases the abnormalities found in renal function were mild.
      CONCLUSION: Patients evincing renal dysfunction 6 months after AUR showed
      permanent impairment in tubular function, whereas glomerular permeability had
      partially recovered. Although this may be explained in part by chronic
      obstruction prior to AUR and although the impairment was mild in most cases,
      these findings stress the importance of urgent treatment of AUR to avoid the
      development of renal failure.

PMID- 11291688
TI  - Hydrophilic versus non-coated catheters for intermittent catheterization.
AB  - Since Lapides reintroduced clean intermittent catheterization (CIC) in 1972, this
      procedure has been used routinely in individualized programmes for bladder
      evacuation in various bladder disorders. It has been suggested that in clinical
      practice hydrophilic catheters are preferable to non-coated catheters. In
      reviewing the literature on CIC, many of the reports were found to rely on data
      from non-randomized retrospective studies. In some recent prospective studies,
      involving a limited number of patients, hydrophilic and non-coated catheters have
      been evaluated and compared, especially with regard to bacteriuria and urethral
      irritation. The available data indicate that using hydrophilic catheters for CIC
      may induce lower rates of bacteriuria and long-term urethral complications such
      as urethral strictures. However, to reach a reliable conclusion about the
      supposed advantage of the hydrophilic catheters, there is a need for a
      prospective, randomized long-term multicentre study. It is important in such a
      study to define patient characteristics including age, gender, diagnosis of
      bladder dysfunction, reason for CIC, physical and mental handicap, manual
      dexterity and previous treatments. Effect parameters should include number of
      catheterizations, urinary tract infection, early and long-term urethral
      complications, patient satisfaction, preferences and dropout rates. It is
      obligatory to include factors such as cost-benefit and cost-effectiveness.

PMID- 11291689
TI  - Determination of serum prostate-specific antigen-alpha1-antichymotrypsin complex
      for diagnosis of prostate cancer in Japanese cases.
AB  - OBJECTIVE: The clinical utility of the determination of serum prostate-specific
      antigen-alpha1-antichymotrypsin complex (PSA-ACT) for the diagnosis of prostate
      cancer, especially in cases in the diagnostic gray zone, is still unclear.
      MATERIAL AND METHODS: With the use of a newly approved enzyme immunoassay for the
      detection of PSA-ACT, 907 sera, including those from non-urological benign and
      malignant diseases, were analysed. RESULTS: Serum values of PSA-ACT in non
      prostate cancer males increased according to age from the 40s to 70s. The serum
      values were high only in the patients with prostatic diseases and, in prostate
      cancer patients, the values became high as the clinical stage progressed. By
      receiver-operating characteristic analysis significantly better results in PSA
      ACT than total PSA were observed. In the group with a total PSA of 2-20 ng/ml,
      the detection of PSA-ACT showed better results, although not significantly so,
      than the free-to-total PSA ratio. CONCLUSIONS: The detection of PSA-ACT showed a
      high clinical utility in the diagnosis of prostate cancer. Therefore, it may
      replace total PSA determination.

PMID- 11291690
TI  - Histo-blood group A antigen expression in pig kidneys--implication for ABO
      incompatible pig-to-human xenotransplantation.
AB  - OBJECTIVE: There is a relative shortage of donor organs for clinical
      transplantation, and the use of animal organs is being considered. A clinical
      trial was performed connecting pig kidneys to the circulation of a dialysis
      patient. MATERIAL AND METHODS: A pig kidney was, after plasmapheresis,
      extracorporeally connected to the circulation of a volunteer dialysis patient.
      The patient was of blood group B and the pig of blood group A. RESULTS: The
      experiment gave rise to a strong humoral immune response where the xenoantibodies
      were shown to be of immunoglobulin G (IgG), IgM and IgA immunoglobulin classes,
      recognizing mainly the Gal alpha1-3Gal epitope and the anti-A antibodies was
      exclusively of IgM type, recognizing the blood group A trisaccharide.
      Immunohistological examinations of blood group A pig kidneys revealed that blood
      group A antigens are located in the distal tubules, thin and thick tubules of
      Henle and the epithelium of the collecting ducts but absent in proximal tubules,
      glomeruli, large vessels and capillaries. In the perfused kidney, a patchy
      destruction of tubular cells was found and these segments stained positive for
      blood group A antigens and had a codeposition of human IgM antibodies and
      complement components. Tubular segments which were apparently normal were all
      negative for blood group A antigens but strongly expressed the Gal alpha1
      xenoantigen. CONCLUSION: In this patient, challenged simultaneously with
      carbohydrate antigen epitopes representing both the ABO and the xenobarrier, the
      humoral immune response differed concerning the immunoglobulin classes induced.
      The low remaining anti-A titre after plasmapheresis was probably sufficient to
      cause destruction of A antigen-positive tubular cells, while the corresponding
      Gal alpha1-xenoantigen-positive cells were structurally intact. This case
      confirms that in future xenotransplantation, matching for the ABO system has to
      be undertaken in the same way as in human allotransplantation.

PMID- 11291691
TI  - Microproteinuria and long-term prognosis with respect to renal function and
      survival in normotensive and hypertensive women--a 24-year follow-up of a
      representative population sample of women in Gothenburg, Sweden.
AB  - OBJECTIVE: This study aimed to assess albuminuria and subclinical proteinuria,
      their association with hypertension and their role as predictors of hypertension,
      impaired renal function and mortality. MATERIAL AND METHODS: A baseline
      population study comprising 1462 women in five different age groups in
      Gothenburg, Sweden, was carried out in 1968-69. Comprehensive clinical
      examinations and laboratory tests were performed, including blood pressure
      measurement and an Albustix test. A systematic subsample of women additionally
      collected a 24 h urine sample for quantitative protein analysis. Values of
      urinary protein (u-protein) excretion between 80 and 300 mg/24 h were defined as
      microproteinuria. The results described in this paper are based on a 24-year
      follow-up. RESULTS: The baseline Albustix test was positive in 6.8% of 1458
      women, from whom a urine sample was obtained. Of 741 baseline urine collections
      for u-protein excretion, 16.9% were in the microproteinuric range (80-300 mg/24
      h), 1.1% in the macroproteinuric range (> 300 mg/24 h) and 82.1% in the
      normoproteinuric range (< 80 mg/24 h). Hypertension was more common in Albustix
      positive women than in those with negative Albustix, and hypertension was also
      more prevalent in women with microproteinuria than in women with
      normoproteinuria. Neither positive Albustix nor microproteinuria was related to
      later renal impairment. Hypertension was associated with increased mortality in
      both Albustix-positive and Albustix-negative women, and in women with both
      normoproteinuria and microproteinuria at baseline. The mortality ratio during the
      follow-up period was, however, not significantly influenced by positive Albustix
      or by microproteinuria at baseline, in either hypertensive or non-hypertensive
      women. CONCLUSIONS: This study demonstrated that both a positive Albustix test
      and microproteinuria were associated with hypertension. Hypertension at baseline
      increased the risk for death during the follow-up period, while neither
      albuminuria, defined as a positive Albustix test, nor microproteinuria was
      associated with an impaired long-term prognosis with respect to renal function or
      survival in this cohort of Swedish middle-aged women during 24 years of follow
      up. Microproteinuria in otherwise healthy normotensive or hypertensive women does
      not appear to impair the long-term prognosis.

PMID- 11291692
TI  - Physical activity, muscle performance and quality of life in patients treated
      with chronic peritoneal dialysis.
AB  - OBJECTIVE: Today's medical treatment of patients with end-stage renal failure has
      increased their opportunities for an active lifestyle. The aim of this study was
      to describe the muscle performance, level of physical activity, independence in
      activities of daily living and quality of life in patients treated with chronic
      peritoneal dialysis. MATERIAL AND METHODS: The study investigated 33 patients (30
      81 years old) treated with chronic peritoneal dialysis. The results were compared
      with an age-matched healthy reference group. Muscle mass was determined by
      measuring total body potassium, while maximal grip strength was measured with an
      electric force transducer. The ability to perform heel-lifts, walking speed and
      level of physical activity were also assessed, along with the extent to which
      patients were independent in activities of daily living (ADL) and satisfied with
      their health. RESULTS: Total body potassium was 97 +/- 11.6% of normal and
      correlated positively with the maximal grip strength (r = 0.658, p < 0.0002) and
      the maximal walking speed (r = 0.558, p < 0.0027). Maximal grip strength was 70%
      of the reference, the ability to perform heel-lifts was 49% of the reference, the
      walking speed was 85% the reference and the level of physical activity was 56% of
      expected. The patients were independent in ADL to a great extent and 52% of the
      patients were satisfied with their health. CONCLUSION: The peritoneal dialysis
      patients had a relatively good quality of life and were largely independent in
      ADL Further studies are needed to investigate whether it is possible to improve
      muscle performance and the level of physical activity with exercise and muscle
      training in these patients.

PMID- 11291693
TI  - Calcified seminal vesicles and vasa deferentia: "beware or be aware".
AB  - Calcification of the seminal vesicles and vasa deferentia is rare. Only the
      second idiopathic case recorded is presented herein. This case highlights the
      need to exclude serious, but treatable diseases associated with this condition,
      which are not generally considered on initial presentation.

PMID- 11291694
TI  - [Scarlet fever and other infections from Streptococcus pyogenes].

PMID- 11291695
TI  - Persistent pulmonary infiltrates in a 16-year-old asthmatic boy.

PMID- 11291696
TI  - Automated   external   defibrillators   improving   survival after   sudden
      cardiac   arrest.

PMID- 11291697
TI  - Spending for   health care   rising again    while some   insurers report  
      increased   profits.

PMID- 11291698
TI  - Cleveland Clinic   plans medical   school by 2003.

PMID- 11291699
TI  - The cat can stay--maybe.

PMID- 11291700
TI  - Recurrent mass in the anterior maxilla.

PMID- 11291701
TI  - Differentiating early malignant lung tumors from inflammatory nodules to minimize
      the use of video-assisted thoracoscopic surgery or open biopsy to establish a
      diagnosis.
AB  - To decrease the frequency of video-assisted thoracoscopic surgery (VATS) biopsy
      being used to diagnose inflammatory nodules, we studied the clinicopathological
      findings of lung cancers and inflammatory nodules diagnosed by VATS or open-lung
      biopsy. We studied 46 lung cancers and 47 inflammatory nodules smaller than 30mm
      in diameter diagnosed by VATS or open-lung biopsy. While the computed tomography
      (CT) findings were not significantly different between lung cancers and
      inflammatory nodules, N1 or N2 lung cancers more frequently showed distinct
      malignant features on CT than T1N0M0 lung cancers (P < 0.05). A review of
      previous chest X-ray films revealed that those of inflammatory nodules showed new
      nodules more frequently and nodular enlargement less frequently than those of
      lung cancer (P < 0.01). Of 13 lung cancers that showed nodular enlargement during
      a mean 15-month period, 12 were T1N0M0. Nondiagnosable small lung nodules, which
      had few malignant features on CT and had newly appeared on a chest X-ray film,
      were more likely to be inflammatory nodules than lung cancers; and even if they
      were lung cancers, the tumor stage was usually T1N0M0. Thus, to decrease the
      incidence of VATS biopsy being performed for inflammatory nodules, intensive
      follow-up by CT until slight nodular enlargement becomes evident could be a means
      of revealing nondiagnosable small lung nodules without distinct malignant
      findings, except for nodules found to be enlarging on a review of retrospective
      films.

PMID- 11291702
TI  - Surgical treatment for chronic pulmonary thromboembolism under cardiopulmonary
      bypass with selective cerebral perfusion.
AB  - The median sternotomy approach for the treatment of chronic pulmonary
      thromboembolism was recently improved by Daily, Jamieson, and coworkers who
      adopted it for use under cardiopulmonary bypass with intermittent circulatory
      arrest; however, we have sometimes found that the circulatory arrest time was too
      short to complete thromboendarterectomy. Therefore, we attempted to perform a
      selective cerebral perfusion technique to extend the endarterectomy time.
      Although we noted slight back-bleeding from the bronchial arteries, we were able
      to extend the endarterectomy time without causing any postoperative delirium. We
      conclude that the median sternotomy approach using cardiopulmonary bypass with
      selective cerebral perfusion may be the best option for extending the
      thromboendarterectomy time.

PMID- 11291703
TI  - A previous mastectomy does not increase sternal complications after coronary
      artery bypass grafting regardless of whether an internal mammary artery is used.
AB  - A mastectomy for breast cancer may alter the selection of grafts or the
      postoperative outcomes after coronary artery bypass grafting (CABG). To clarify
      these points, a retrospective analysis of patients who underwent CABG after a
      mastectomy was undertaken. A total of 19 mastectomy patients (13 left, 6 right,
      and 1 bilateral mastectomy) were identified prior to CABG, and their
      perioperative data as well as late outcomes were examined. The studied group
      consisted of all females with a mean age of 68.8 +/- 6.2 years. The internal
      mammary artery (IMA) was used in 14 (73.7%) patients; however, there were no
      patients in whom bilateral IMAs were harvested. Among these 14 patients, an
      ipsilateral IMA was harvested in 6 and a contralateral IMA in 8. Alternative
      grafts were selected in 6 patients. A contralateral IMA or other graft conduits
      were utilized instead of an ipsilateral IMA. There were no in-hospital deaths or
      sternal wound complications. With a mean follow-up of 2.6 years, 3 patients died
      (1 cardiac death and 2 noncardiac deaths) and 1 patient developed angina due to
      de-novo coronary artery stenosis. In patients who have undergone a previous
      mastectomy, CABG using a single IMA is considered to be safe. If the IMA has good
      pulsation and if IMA harvesting is not difficult, even after a mastectomy, it can
      be used as a graft conduit without increasing the risk of sternal wound
      complications.

PMID- 11291704
TI  - Evaluation of the predictors of choledocholithiasis: comparative analysis of
      clinical, biochemical, radiological, radionuclear, and intraoperative parameters.
AB  - This prospective study was performed to assess the predictive ability of the
      various indicators of common bile duct (CBD) calculi, individually or in
      combination, by analyzing 88 patients with gallstone disease. The patients were
      classified into two groups according to the presence of 10 predefined criteria.
      Of 53 patients with one or more risk factors (group 2), 26 harbored CBD calculi;
      none of 35 patients with no risk factors (group 1) had CBD stones. Jaundice
      correlated best, with a sensitivity of 69%; and pancreatitis had the lowest
      sensitivity (12%). Elevated serum bilirubin and alkaline phosphatase levels
      correlated better than liver enzymes and serum amylase. The sensitivity and
      negative predictive value of cholescintigraphy scanning for diagnosing CBD
      calculi were better than those of ultrasonography, the sensitivity being 84%
      versus 50% and the negative predictive value 95% versus 82%. Endoscopic
      retrograde cholangiopancreaticography was successful in 94% of the patients, and
      CBD calculi were diagnosed in 74%. Moreover, peroperative cholangiography was
      100% sensitive with no false-positive results. Ultimately, a palpable stone at
      surgery was the best predictor. When all the criteria were analyzed, it was found
      that as the number of criteria increased so did the percentage of patients
      harboring CBD calculi.

PMID- 11291705
TI  - Long-term results of kidney transplantation between HLA-identical siblings.
AB  - Long-term data on HLA-identical renal transplants are scarce, and the advantages
      of using cyclosporine (CsA) over azathioprine (AZA) have yet to be elucidated. In
      68 recipients from HLA-identical donors (37 under AZA-steroids and 31 under CsA
      steroids), we estimated the graft and patient survival to posttransplant 120
      months, and compared the results between patients on different protocols.
      Episodes of rejection, causes of graft loss or patient death, and longterm
      complications were also compared retrospectively. The 10-year patient/graft
      survivals were comparable: 82.7/67.6% for the AZA and 78.4/63.5% for the CsA
      patients. The incidence of acute rejection during the first year after transplant
      was also comparable. We lost 25 grafts. The major causes of graft loss were
      patient death (7/13 in AZA and 5/12 in CsA patients) and chronic rejection (3/13
      in AZA and 3/12 in CsA patients). Four grafts were lost due to poor compliance.
      We lost 12 patients due mostly to cerebrovascular disease and infections. There
      was no difference in the prevalence of complications between patients. In
      conclusion, the long-term outcome was excellent in this subgroup of transplant
      patients. We could not find any advantages of using CsA over AZA in these
      patients after a long-term follow-up. To achieve better results, continued
      attention should be paid to the prevention of poor compliance and complications.

PMID- 11291706
TI  - Results of performing mesh plug repair for groin hernias.
AB  - The simplicity and good postoperative results of mesh plug repair for groin
      hernias have been reported in numerous articles. We have been performing this
      procedure in our department for more than 5 years, and the present study was
      conducted to reexamine its clinical outcome from our viewpoint. A total of 224
      patients with a collective 244 groin hernias underwent mesh plug repair between
      March 1993 and August 1998. There were 155 (63.5%) indirect hernias, 79 (32.4%)
      direct hernias, 2 (0.8%) femoral hernias, and 8 (3.3%) compound hernias; 27
      (11.1%) were recurrent hernias. Two plugs were inserted in all the compound
      hernias and in two of the direct hernias with a diffuse weak inguinal floor. The
      mean operating time was 32.2min. The complications that developed during this
      study were continuous pain in four patients, seroma in two, and hematoma in one.
      The rates of recurrence were 0% for indirect hernias and 12.7% for direct
      hernias. The patients in whom recurrence developed underwent mesh plug repair
      again and have had no further recurrence. Our experience showed mesh plug repair
      to be an excellent technique for indirect hernias or recurrent hernias after mesh
      repair, but it might be unsuitable for direct hernias with a diffuse bulging
      weakness in the floor of the inguinal canal.

PMID- 11291707
TI  - Analysis of the development of normal foregut and tracheoesophageal fistula in an
      adriamycin rat model using three-dimensional image reconstruction.
AB  - To examine the developmental process of the normal trachea and esophagus and
      their maldevelopment leading to tracheoesophageal fistula (TEF), we performed
      three-dimensional (3-D) image reconstruction of the developing foregut in normal
      and adriamycin (ADM)-induced TEF rats. Microscopic images of serial sections of
      embryos from seven normal and 14 ADM-treated rats killed every half a day after
      11-14 days' gestation were traced and reconstructed using a 3-D construction
      imaging system (TRI, RATOC System Engineering, Tokyo, Japan). In the normal
      embryos, the lung bud appeared just below the pharyngeal foregut on day 11 and it
      elongated caudally to shape into the trachea as they grew. A 'tracheoesophageal
      septum" did not emerge. In the TEF embryos, although the lung bud appeared in a
      similar position on day 11, the trachea and esophagus did not separate and only a
      common foregut tube elongated caudally, then bilateral bronchial primordia
      emerged directly from it. Furthermore, abnormal development of the notochord was
      evident, being retarded in separation from the foregut, finally descending along
      a more ventral course and bending sharply around the level of the bifurcation.
      Microscopically, less mesenchymal cellularity around the foregut was noted in the
      TEF embryos. The trachea seemed to be formed only by caudal elongation of the
      lung bud in the normal embryos. In the ADM-induced TEF embryos, the upper foregut
      appeared to develop only into the trachea, and this maldevelopment may be
      implicated in the abnormal interaction between the foregut and the surrounding
      mesenchyme.

PMID- 11291708
TI  - Kupffer cell function in ischemic and nonischemic livers after hepatic partial
      ischemia/reperfusion.
AB  - Hepatic partial ischemic/reperfusion (I/R) injury, in which ischemic and
      nonischemic areas of the liver are likely to respond to each other after
      reperfusion, often occurs following hepatobiliary surgical procedures. Kupffer
      cells (KCs) are considered to play a major role in hepatic I/R injury. To study
      the activation of KCs in ischemic and nonischemic liver tissues following hepatic
      I/R, we investigated the superoxide generation and proinflammatory cytokine
      production of KCs in both liver parts in a rat model of partial hepatic I/R
      injury. KC superoxide generation in the ischemic and nonischemic lobes was
      upregulated 6 and 24 h after reperfusion, respectively, and then accelerated. The
      production of interleukin-1beta (IL-1beta) by KCs in the ischemic lobes increased
      during the early and late phases, 6 h and 48-72 h after reperfusion,
      respectively. A late increase in IL-1beta production was also observed in the
      nonischemic lobes. Production of tumor necrosis factor-alpha (TNF-alpha)
      increased 6-24h after reperfusion in both lobes. Upregulation of IL-1beta mRNA in
      the ischemic lobes preceded the upregulation of TNF-alpha mRNA in both lobes. The
      hepatic partial I/R process results in activation of KCs in ischemic and
      nonischemic areas of the liver. The KCs are activated during the early phase
      after reperfusion in the ischemic areas, followed by activation in both the
      ischemic and nonischemic areas. This could be a cause of liver dysfunction after
      partial hepatic I/R during surgery.

PMID- 11291709
TI  - Tamoxifen-failed male breast cancer with a high level of circulating estrogen:
      report of a case.
AB  - We report herein the case of a 40-year-old man with grade II invasive ductal
      carcinoma of the breast (pT1, pN0, M0: stage I) in whom a recurrence developed
      shortly after completion of a 2-year course of tamoxifen and 5-fluorouracil
      therapy following a mastectomy. Although the metastatic tumor was estrogen
      receptor-positive, hormone therapy combined with chemotherapy had no significant
      effect on tumor growth, and the patient died from disseminated tumors 2 years 6
      months after completion of the adjuvant therapy. It is noteworthy that the
      circulating estradiol level increased from 18.0 to 892.3 pg/ml during the period
      of tumor progression and dissemination. We interpret these findings as an
      indication of high aromatase activity in the metastatic tumors. We suggest that
      extending tamoxifen treatment to 5 years or longer be recommended for the
      standard adjuvant hormone therapy of male breast cancer to prevent the early
      recurrence of hormone-responsive disease.

PMID- 11291710
TI  - Targeting adjuvant brachytherapy for a superior sulcus tumor: report of two
      cases.
AB  - We report herein the cases of two patients who underwent complete resection of a
      superior sulcus tumor (SST) plus adjuvant brachytherapy, with the area to be
      irradiated determined by a computer program system designed to minimize
      unnecessary irradiation to the normal components and to optimize the effect on
      the targeted area. Although the efficacy of brachytherapy on the inhibition of
      local relapse needs to be observed over a long period, the selective and
      alternative use of delivering adjuvant brachytherapy by this method appears to
      enhance the quality of life of patients with a SST.

PMID- 11291711
TI  - Type IV hiatal hernia post laparoscopic Nissen fundoplication: report of a case.
AB  - A postoperative hiatal hernia is a rare but serious complication of
      fundoplication. We report herein a 62-year-old female who presented with
      abdominal pain and vomiting 2 years following laparoscopic Nissen fundoplication.
      At laparotomy, the stomach and the transverse colon were intrathoracic (type IV
      hiatal hernia); the esophageal hiatus was markedly dilated with no evidence that
      they had been approximated. At 18 months follow-up, she is doing very well apart
      from occasional heartburn. A high index of suspicion is needed to diagnose
      postoperative hiatal hernias. A routine closure of the crura with nonabsorbable
      suture material and an avoidance of iatrogenic pneumothorax may help to reduce
      the occurrence of this problem.

PMID- 11291712
TI  - Long-term survival after gastric cancer and liver and paraaortic lymph node
      metastases: report of a case.
AB  - We report the case of a 46-year-old man in whom successful resection of carcinoma
      of the stomach with liver and paraaortic lymph node metastases was carried out.
      The carcinoma was removed completely with combined resection of the lower
      esophagus, total stomach, distal pancreas, spleen, two metastatic liver nodes,
      and groups 1 and 2 and abdominal paraaortic lymph nodes. Adjuvant chemotherapy
      was administered postoperatively. The patient is currently well with a grade 1
      performance status and no signs of recurrence 12 years after his operation. This
      experience suggests that even the presence of metastatic paraaortic lymph nodes
      and liver metastases is not necessarily a contraindication to surgery when the
      carcinoma can be resected curatively and safely.

PMID- 11291713
TI  - Perforated leiomyosarcoma of Meckel's diverticulum: report of a case.
AB  - We report herein a case of leiomyosarcoma of Meckel's diverticulum which
      presented as a rare manifestation of perforation. A previously healthy 63-year
      old man was referred to the Tetsujinkai Eniwa hospital following the sudden
      development of acute abdominal pain. Abdominal computed tomography revealed a
      solid mass in the pelvic cavity, and an emergency operation was performed under a
      provisional diagnosis of peritonitis associated with a pelvic tumor. A perforated
      tumoral mass was found in Meckel's diverticulum. Segmental resection of the
      ileum, including the tumor-bearing diverticulum, was performed along with
      regional lymph node dissection. Histologic examination revealed the lesion to be
      leiomyosarcoma.

PMID- 11291714
TI  - Transverse colonic cancer presenting as an anterior abdominal wall abscess:
      report of a case.
AB  - An 81-year-old man who had been aware of a right anterior abdominal mass for 1
      week was admitted to our hospital on July 3, 1999, after the mass had perforated
      and was secreting mucinous purulent material. Computed tomography clearly showed
      an anterior abdominal wall abscess and a large intraabdominal tumor that
      contained a fistula-like structure. Barium enema revealed an apple-core sign at
      the transverse colon, with a fistula that connected the colon to the abscess
      cavity. Transverse colonic cancer complicated by an anterior abdominal wall
      abscess was diagnosed, and an extended right hemicolectomy was performed. We did
      not perform en bloc excision of the full thickness of the anterior abdominal
      wall, including the abscess, because the defect was determined to be too large to
      repair. Thus, when curative resection is not feasible, as in our patient,
      resection of the primary tumor with en bloc partial resection of the adherent
      parietal wall should be performed if possible, as this procedure has the
      potential to improve the postoperative quality of life of the patient.

PMID- 11291715
TI  - Malignant sarcomatoid tumor of the liver: report of a case.
AB  - A 65-year-old man was referred to our hospital for treatment of a liver tumor.
      Abdominal ultrasonography (US) demonstrated a low echoic mass in the S2-S4 region
      of the liver, which was confirmed by abdominal computed tomography (CT). In the
      delayed phase of angio-CT, the inside of the mass was not enhanced. Abdominal
      angiography showed a hypovascular area in the liver. An extended left lobectomy
      was performed. Macroscopically, the tumor was 9.5 x 9.5 cm in size, and on cross
      section, it was white and clearly demarcated from the surrounding tissue.
      Microscopic observation of hematoxylin-eosin-stained specimens did not show any
      glandular or trabecular formation. Histologically, there was diffuse
      proliferation of atypical spindle cells that had hyperchromatic, short, spindle
      shaped nuclei, and pale cytoplasm with poor intercellular adhesion. The
      nontumorous tissue was almost normal with no sign of cirrhosis.
      Immunohistochemical examination showed that the spindle cells were positive for
      vimentin and cytokeratins (AE1/AE3, CAM 5.2), but negative for all other markers.
      The final diagnosis was a sarcomatoid carcinoma, the origin of which was not able
      to be confirmed immunohistochemically. This case of a primary hepatic tumor
      composed of malignant cells with sarcomatous features is described, and the
      immunohistochemical findings are discussed.

PMID- 11291716
TI  - Pleural dissemination as a complication of preoperative percutaneous transhepatic
      biliary drainage for hilar cholangiocarcinoma: report of a case.
AB  - One potential risk of percutaneous transhepatic biliary drainage is tumor seeding
      along the catheter tract. A 57-year-old woman with obstructive jaundice due to
      hilar cholangiocarcinoma underwent an extended left hepatic lobectomy, a regional
      lymph node dissection, and a right hepaticojejunostomy 2 weeks after percutaneous
      transhepatic biliary drainage. Multiple right pleural masses were found on a
      chest radiogram 14 months after the operation. No recurrent lesions were detected
      in the abdominal cavity. A right panpleuropneumonectomy was performed; however,
      the patient died of respiratory failure due to tumor recurrence 9 months after
      the second operation. Preoperative percutaneous transhepatich biliary drainage
      was considered to have resulted in pleural implantation.

PMID- 11291717
TI  - Mixed duct-acinar-islet cell tumor of the pancreas: report of a case.
AB  - A 72-year-old Japanese woman presented at our hospital complaining of altered
      consciousness on arising every morning. The laboratory findings showed
      hypoglycemia and hyperinsulinemia. Abdominal ultrasonography revealed a tumor in
      the body of the pancreas. With a diagnosis of insulinoma, a surgical excision of
      the tumor was performed. A light microscopic examination and an
      immunohistochemical study revealed the tumor to consist of duct, acinar, and
      islet cell components. Mixed tumors of the pancreas are rare, and their clinical
      features and pathogenesis remain unclear. A further accumulation of clinical
      cases as well as a large number of histopathological studies on these rare mixed
      tumors is needed.

PMID- 11291718
TI  - Concomitant duodenal and pancreatic metastases from renal cell carcinoma: report
      of a case.
AB  - The pancreas and duodenum are uncommon sites for metastasis from renal cell
      carcinoma. Pancreatic or small intestinal metastases mainly occur when there is
      widespread nodal and visceral involvement and evidence of metastatic disease
      elsewhere in the body. We describe herein the case of a 68-year-old man in whom
      metastases arising from renal cell carcinoma developed concomitantly in the
      duodenum and pancreas. The patient presented with duodenal bleeding; but as no
      other metastatic lesions were observed at the time of surgery, total
      pancreatectomy with duodenetomy was performed. We believe that metastases may
      easily develop in the duodenum and pancreas owing to the similar tissue
      characteristics.

PMID- 11291719
TI  - Left diaphragmatic eventration with a suprapubic spleen: report of a case.
AB  - Diaphragmatic defects such as eventration and hernia are known to be associated
      with a high-sited, sometimes intrathoracic spleen. We report here a unique case
      of an 8-year-old boy found to have a left congenital diaphragmatic eventration
      and a suprapubic wandering spleen after presenting with symptoms of an "acute
      abdomen" due to torsion of the splenic pedicle. To our knowledge only one other
      case of a similar paradoxical association of these anomalies has been reported
      before; interestingly, in this patient splenic infarction had also resulted
      secondary to splenic torsion. We recommend careful evaluation of the location and
      vascular status of the spleen in all patients with congenital diaphragmatic
      defects due to the common occurrence of splenic vascular insult.

PMID- 11291720
TI  - Traction-type heart stabilizer for off-pump coronary bypass grafting.
AB  - We designed a stabilizer to assist us in performing coronary artery bypass
      grafting on the beating heart. The stabilizer consists of a U-shaped holed
      platform, an articulating arm, and a clamp for attachment to an ordinary sternal
      retractor. The target coronary artery is dissected, then two elastic sutures, 15
      20mm apart, are wrapped around it, proximal and distal to the anastomotic site.
      These sutures for traction are passed through holes in the U-shaped platform and
      tied. This traction immobilizes the target area of the coronary artery. The
      stabilizer described herein provides good exposure and steady immobilization to
      enable anastmosis to be more easily performed in the beating heart.

PMID- 11291721
TI  - The value of ultrasound-guided fine-needle aspiration cytology for thyroid
      nodules: an assessment of its diagnostic potential and pitfalls.
AB  - This study was conducted to assess the diagnostic potential and pitfalls of
      performing fine-needle aspiration cytology (FNAC) for thyroid nodules. We
      retrospectively analyzed 1,012 aspirated samples obtained from 806 thyroid
      nodules by the ultrasound (US)-guided method. Of these 806 nodules, 226 (31%) had
      been surgically treated, 152 (67%) of which were histologically diagnosed as
      malignant. The rate of sufficient aspirate was 82%, being lower in nodules with a
      diameter of less than 5mm (73%, P = 0.10); either calcified (77%, P = 0.043) or
      benign (72%, P = 0.0002). The accuracy of FNAC was 75%, the rate of indeterminate
      diagnosis was 16%, the false negative rate was 13%, and the positive malignancy
      rate was 99%. The rate of indeterminate diagnosis was higher in adenomatous
      goiter, follicular carcinoma, and malignant lymphoma, at P = 0.015, P = 0.0008,
      and P = 0.035, respectively. The accuracy was lower in follicular carcinoma and
      malignant lymphoma (both at P = 0.013). Sufficient aspirate was finally obtained
      from 701 (87%) of the 806 nodules by repeated aspiration. Of 152 malignant
      nodules, 28 (18%) were diagnosed after two or more aspirations, and the accuracy
      was improved to 81% by repeating the procedure. These findings indicated that
      repeated aspiration may be a simple and effective method of improving the
      diagnostic potential of FNAC.

PMID- 11291722
TI  - Commissural effects in the otolith system.
AB  - We examined whether otolith-activated second- and third-order vestibular nucleus
      neurons received commissural inhibition from the contralateral otolithic macula
      oriented in the same geometric plane. For this purpose we performed intracellular
      recording in vestibular nucleus neurons after stimulation of the ipsi- and
      contralateral utricular and saccular nerves. More than half (41/72) of the
      utricular-activated second-order vestibular nucleus neurons received commissural
      inhibition from the contralateral utricular nerve. The remaining neurons (31/72)
      showed no visible response to contralateral utricular nerve stimulation. About
      half (17/36) of utricular-activated third-order neurons also received commissural
      inhibition from the contralateral utricular nerve. Approximately 10% (7/67) of
      saccular-activated second-order vestibular neurons received polysynaptic
      commissural inhibition, whereas 16% (11/67) received commissural facilitation.
      The majority (49/67) of saccular second-order vestibular neurons, and almost all
      (22/23) third-order neurons, showed no visible response to stimulation of the
      contralateral saccular nerve. The present findings suggest that many utricular
      activated vestibular nucleus neurons receive commissural inhibition, which may
      provide a mechanism for increasing the sensitivity of vestibular neurons to
      horizontal linear acceleration and lateral tilt of the head. Commissural
      inhibition in the saccular system was less prominent than in the utricular
      system.

PMID- 11291723
TI  - Role of the human motor cortex in rapid motor learning.
AB  - Recent studies suggest that the human primary motor cortex (M1) is involved in
      motor learning, but the nature of that involvement is not clear. Here, learning
      related changes in M1 excitability were studied with transcranial magnetic
      stimulation (TMS) while na subjects practiced either a ballistic or a ramp pinch
      task to the 0.5-Hz beat of a metronome. Subjects rapidly learned to optimize
      ballistic contractions as indicated by a significant increase in peak pinch
      acceleration and peak force after the 60-min practice epoch. The increase in
      force and acceleration was associated with an increase in motor evoked potential
      (MEP) amplitude in a muscle involved in the training (flexor policis brevis) but
      not in a muscle unrelated to the task (abductor digiti minimi). MEPs returned to
      their baseline amplitude after subjects had acquired the new skill, whereas no
      practice-induced changes in MEP amplitude were observed after subjects had
      overlearned the task, or after practicing slow ramp pinches. Since the changes in
      MEP amplitude were observed only after TMS of M1 but not after direct stimulation
      of the corticospinal tract, these findings indicate task- and effector-specific
      involvement of human M1 in rapid motor learning.

PMID- 11291724
TI  - The effects of stance configuration and target distance on reaching. I. Movement
      preparation.
AB  - The aim of the present study was to investigate the relationship between the
      focal and postural components of a functional movement during the preparatory
      phase of a task. The contribution of the arms, trunk, and legs were varied by
      having subjects reach for two targets within and two beyond arm's length. In
      addition, the degree of postural stability was manipulated by varying the size of
      the base of support (BoS). Nine subjects reached and grasped a dowel placed at
      four locations while standing on a force plate with their feet in a parallel or
      step stance (right foot forward) under simple reaction-time (RT) conditions.
      Anticipatory postural adjustments (APAs) occurring prior to arm movement and RTs
      were analyzed. APAs varied depending on the demands of the task. For movements
      within arm's length, subjects selected different strategies to initiate the
      movement. However, for movements beyond arm's length, all subjects used the same
      strategy: the center of pressure (CoP) was shifted posteriorly, which resulted in
      the center of mass (CoM) moving towards the target. Target distance and BoS had
      no effect on the onset of APAs. In contrast, amplitude and duration of APAs
      increased linearly with target distance, and amplitude was always greater during
      the more posturally stable BoS configuration. Although wrist RT increased
      linearly with movement amplitude for both stance configurations, the rate of
      change was less under the more stable BoS. These results suggest that, during the
      performance of a functional task, dynamic changes that occur in the trunk and
      lower extremities prior to initiation of arm movement serve not only to stabilize
      the body, but are also used to initiate and assist whole-body reaching.

PMID- 11291725
TI  - Expansion of receptive fields in raccoon somatosensory cortex in vivo by GABA(A)
      receptor antagonism: implications for cortical reorganization.
AB  - The effect of antagonism of GABA(A) receptors on the receptive fields of raccoon
      primary somatosensory cortical neurons was tested using microiontophoretic
      administration of bicuculline methiodide (BMI). The size of cutaneous receptive
      fields was examined using minimal suprathreshold mechanical stimulation before,
      during, and after BMI administration. In 65 of 102 rapidly adapting neurons, BMI
      produced a clear expansion of the receptive field. The mean increase in receptive
      field size was 286%. The receptive fields on the distal digit, which were
      initially smaller, showed smaller increases in absolute area than more proximal
      receptive fields, but the percentage increase did not vary with location. Greater
      expansion was seen in superficially located neurons than in those below 800
      microm. Of particular significance was the finding that the expansion of
      receptive fields produced by BMI never extended from one digit onto an adjacent
      digit or onto the palm, even when the original receptive field was at the base of
      a digit. This finding indicates that intracortical GABAergic inhibition is
      insufficient to explain cortical reorganization following digit amputation.

PMID- 11291726
TI  - Granule cells are the main source of excitatory input to a subpopulation of
      GABAergic hippocampal neurons as revealed by electron microscopic double staining
      for zinc histochemistry and parvalbumin immunocytochemistry.
AB  - Immunocytochemistry was combined with a recent modification of Timm's method to
      evaluate semiquantitatively the mossy fiber innervation of dendrites and somata
      of parvalbumin-containing neurons of the hilus of the dentate gyrus and the CA3
      area of Ammon's horn. Using this electron microscopic double staining technique,
      it was found that (1) the overwhelming majority (95%) of terminals forming
      asymmetric synapses with parvalbumin-positive dendrites in the dentate hilus, and
      the strata pyramidale and lucidum of the CA3 area of Ammon's horn, originated
      from granule cells; (2) two-thirds of the asymmetric axosomatic terminals of
      parvalbumin-positive neurons contained zinc; and (3) no zinc-containing axon
      terminals formed synapses with somata or main dendritic shafts of the granule
      cells.

PMID- 11291727
TI  - Reciprocal angular acceleration of the ankle and hip joints during quiet standing
      in humans.
AB  - Human quiet standing is often modeled as a single inverted pendulum rotating
      around the ankle joint, under the assumption that movement around the hip joint
      is quite small. However, several recent studies have shown that movement around
      the hip joint can play a significant role in the efficient maintenance of the
      center of body mass (COM) above the support area. The aim of this study was to
      investigate how coordination between the hip and ankle joints is controlled
      during human quiet standing. Subjects stood quietly for 30 s with their eyes
      either opened (EO) or closed (EC), and we measured subtle angular displacements
      around the ankle (thetaa) and hip (thetah) joints using three highly sensitive
      CCD laser displacement sensors. Reliable data were obtained for both angular
      displacement and angular velocity (the first derivative of the angular
      displacement). Further, measurement error was not predominant, even among the
      angular acceleration data, which were obtained by taking the second derivative of
      the angular displacement. The angular displacement, velocity, and acceleration of
      the hip were found to be significantly greater (P<0.001) than those of the ankle,
      confirming that hip-joint motion cannot be ignored, even during quiet standing.
      We also found that a consistent reciprocal relationship exists between the
      angular accelerations of the hip and ankle joints, namely positive or negative
      angular acceleration of ankle joint is compensated for by oppositely directed
      angular acceleration of the hip joint. Principal component analysis revealed that
      this relationship can be expressed as: thetah=gammathetaa with gamma=-3.15+/-1.24
      and gamma=-3.12+/-1.46 (mean +/-SD) for EO and EC, respectively, where theta is
      the angular acceleration. There was no significant difference in the values of y
      for EO and EC, and these values were in agreement with the theoretical value
      calculated assuming the acceleration of COM was zero. On the other hand, such a
      consistent relationship was never observed for angular displacement itself. These
      results suggest that the angular motions around the hip and ankle joints are not
      to keep the COM at a constant position, but rather to minimize acceleration of
      the COM.

PMID- 11291728
TI  - Suppression of the auditory middle-latency response and evoked gamma-band
      response in a paired-click paradigm.
AB  - When two clicks are presented within 500 ms and the clicks are separated by
      several seconds, a typical finding is a suppression of the amplitude of the P50
      component of the middle-latency auditory-evoked response. In the present study,
      we investigated whether only the P50 or also the earlier components Po, Na, Pa
      and Nb, and the exogenous components N100 and P200 exhibit an amplitude
      suppression to the second click. In addition, we studied the suppression
      behaviour of the auditory-evoked 40-Hz gamma-band response in the time and
      frequency domain. We found a significant amplitude suppression to the second
      click for all components of the auditory-evoked potential following Po, which was
      most pronounced at electrode Cz. When testing the successive peaks and troughs of
      the evoked 40-Hz gamma-band response in the time domain, we found a significant
      amplitude suppression for peaks and troughs with the same latency and polarity as
      the middle-latency components following Po, which was most pronounced at
      electrodes Fz and Cz. Consequently, the amplitude of the 40-Hz evoked gamma-band
      response in the frequency domain paralleled the findings of the time domain, with
      a significant amplitude suppression to the second tone, which was most pronounced
      at electrodes Fz and Cz. Results are discussed with reference to the early
      sensory-gating hypothesis.

PMID- 11291730
TI  - Spatial and temporal modulation of joint stiffness during multijoint movement.
AB  - Joint stiffness measurements during small transient perturbations have suggested
      that stiffness during movement is different from that observed during posture.
      These observations are problematic for theories like the classical equilibrium
      point hypothesis, which suggest that desired trajectories during movement are
      enforced by joint stiffness. We measured arm impedances during large, slow
      perturbations to obtain detailed information about the spatial and temporal
      modulation of stiffness and viscosity during movement. While our measurements of
      stiffness magnitudes during movement generally agreed with the results of
      measurements using fast perturbations, they revealed that joint stiffness
      undergoes stereotyped changes in magnitude and aspect ratio which depend on the
      direction of movement and show a strong dependence on joint angles. Movement
      simulations using measured parameters show that the measured modulation of
      impedance acts as an energy conserving force field to constrain movement. This
      mechanism allows for a computationally simplified account of the execution of
      multijoint movement. While our measurements do not rule out a role for afferent
      feedback in force generation, the observed stereotyped restoring forces can allow
      a dramatic relaxation of the accuracy requirements for forces generated by other
      control mechanisms, such as inverse dynamical models.

PMID- 11291729
TI  - Nitric-oxide-induced cGMP synthesis in cholinergic neurons in the rat brain.
AB  - Nitric oxide (NO)-mediated cGMP synthesis is localized throughout the rat brain
      in close proximity to the NO-synthase-containing structures. However,
      characterization of the cGMP synthesizing structures in terms of co-localization
      with the classical neurotransmitter systems has not yet been reported. Here we
      present evidence, using double immunostaining for cGMP and the vesicular
      acetylcholine transporter, that virtually all of the cholinergic fibers in the
      cerebral cortex and the majority of the cholinergic fibers in the basal ganglia
      accumulate cGMP in response to a NO donor. In these areas, only few cGMP
      containing fibers were observed not to be part of the cholinergic system. Co
      localization between cGMP and the vesicular acetylcholine transporter was only
      observed to a minor degree in the ventral forebrain, the hippocampus, the
      reticular thalamic nucleus, and the nucleus ambiguus. No association of cGMP
      synthesis with the cholinergic system was observed to a similar extent in other
      brain areas. These results, in combination with literature data on the
      distribution of cholinergic receptors in the rat brain, suggest that NO has an
      anterograde and/or retrograde signaling function on subsets of cholinergic
      neurons.

PMID- 11291731
TI  - Distractor effects on pointing: the role of spatial layout.
AB  - There is a debate about how task-irrelevant visual distractors influence motor
      responses. Inconsistent findings in previous studies may reflect the use of
      different spatial layouts. In this study, participants pointed to randomly
      lateralized targets under full viewing conditions, either with or without a
      single distractor present. Distractor location, size, and spacing from the target
      were systematically manipulated while target size and movement amplitude remained
      constant. Larger distractors facilitated reaction times and slowed movement
      times. Distant distractors facilitated only reaction times. Movement endpoints
      were biased away from distractors. The single distractor also modulated perceived
      target size. These results are discussed in the context of current theories of
      the role of visual perception for action control.

PMID- 11291732
TI  - Passive tactile sensory input improves stability during standing.
AB  - The effects of passive tactile cues about body sway on stability during standing
      were evaluated in subjects with a wide range of sensorimotor and balance
      performance. Healthy young adults, diabetic subjects with varying degrees of
      peripheral sensory neuropathy and older subjects aged 70-80 years were studied.
      Body sway was measured when subjects stood on the floor and on a foam rubber mat,
      with or without an applied stimulus that rubbed on the skin at the leg or
      shoulder as the body swayed. The results show that this stimulus reduced body
      sway (mean reduction 24.8%+/-1.5) and thus had a stabilizing effect as big as
      vision or sensory information from the feet. The reduction in sway was not based
      on active touch. The stimulus was not restricted to a particular region of the
      body, but was more effective on the shoulder than the leg, and was more effective
      when standing with eyes shut or when standing on the foam mat. It was also most
      effective in those subjects who had the greatest sway during normal standing.
      Thus, the response appears to be graded with the amplitude of the stimulus. We
      concluded that, if passive sensory input about posture is available, the postural
      control process adapts to this input, modulating postural stabilizing reactions.

PMID- 11291733
TI  - A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is co
      localized with delta-glutamate receptors in postsynaptic densities of parallel
      fiber-Purkinje cell synapses.
AB  - Confocal immunofluorescence microscopy showed strong monocarboxylate transporter
      2 (MCT2) labeling of Purkinje cell bodies and punctate labeling in the molecular
      layer. By immunogold cytochemistry, it could be demonstrated that the MCT2
      immunosignal was concentrated at postsynaptic densities of parallel fiber
      Purkinje cell synapses. The distribution of MCT2 transporters within the
      individual postsynaptic densities mimicked that of the delta2 glutamate receptor,
      as shown by use of two different gold-particle sizes. The MCT2 distribution was
      also compared with the distributions of other monocarboxylate transporters (MCT1
      and MCT4). The MCT1 immunolabeling was localized in the endothelial cells, while
      MCT4 immunogold particles were associated with glial profiles, including those
      abutting the synaptic cleft of the parallel fiber-spine synapses. The
      postsynaptic density (PSD) molecules identified so far can be divided into five
      classes: receptors, their anchoring molecules, molecules involved in signal
      transduction, ion channels, and attachment proteins. Here, we provide evidence
      that this list of molecules must now be extended to comprise an organic molecule
      transporter: the monocarboxylate transporter MCT2. The present data suggest that
      MCT2 has specific transport functions related to the synaptic cleft and that this
      transporter may allow an influx of lactate derived from perisynaptic glial
      processes. The expression of MCT2 in synaptic membranes may allow energy supply
      to be tuned to the excitatory drive.

PMID- 11291734
TI  - Old age affects fingertip forces when restraining an unpredictably loaded object.
AB  - We investigated the effects of old age on the fingertip force responses that
      occurred when a grasped handle was pulled unexpectedly to increase the tangential
      load at the fingertip. These automatic responses, directed normal to the handle
      surface, help prevent slips between the handle and finger. Old adults (average
      age 78 years) responded with large peak fingertip forces compared to young adults
      (average age 30 years), even though the two subject groups showed similar skin
      slipperiness. For step-shaped loads the average response latency was the same for
      young and old subjects (about 80 ms). Thus, these automatic responses are not
      susceptible to the age-related central delays known for simple reaction-time
      tasks. For ramp-shaped loads the average response latency was inversely related
      to load rate. Response latency was 25 ms longer for the Old group versus the
      Young group for loads of 8 N/s, and this difference increased exponentially to a
      110-ms difference for 2-N/s loads. A twofold difference in the tangential force
      required to evoke a response was predicted from linear regressions and can
      account for the latency difference (0.2 N vs 0.4 N threshold for young and old,
      respectively, r=0.93 for both groups). This theoretical elevation in load force
      threshold is consistent with degraded central information processing in old age,
      and the deterioration of cutaneous mechanoreceptors.

PMID- 11291735
TI  - The effect of frequency on the visual perception of relative phase and phase
      variability of two oscillating objects.
AB  - Relative phase has been studied extensively as a measure of interlimb
      coordination. Only two relative phases, namely 0 degrees and 180 degrees, are
      stably produced at the preferred frequency (approximately 1 Hz). When frequency
      is increased, movement at 180 degrees becomes unstable and relative phase
      typically switches to 0 degrees, which remains stable at higher frequencies. The
      current study was designed to investigate the perception of relative phase and of
      phase variability. Observers viewed two circles moving rhythmically in a computer
      display. Mean phases varied from 0 degrees to 180 degrees in 30 degrees steps.
      Phase variability at each mean phase varied from 0 degrees to 5 degrees, 10
      degrees, and 15 degrees phase standard deviation (SD). Frequency of oscillation
      was either 0.75 Hz or 1.25 Hz. One group of ten observers judged mean relative
      phase. Another group judged phase variability. As predicted, increase in
      frequency yielded an increase in perceived phase variability at 180 degrees mean
      phase and other mean phases, but not at 0 degrees mean phase. In contrast,
      increase in actual phase variability affected judgments of 0 degrees mean phase
      most strongly. A second control experiment showed that the frequency effects were
      not produced by changes in display durations or frames per cycle of oscillation.
      The results are consistent with those in studies of interlimb coordination and
      indicate that understanding of interlimb coordination requires further
      investigation of phase perception.

PMID- 11291736
TI  - Aldicarb poisoning.
AB  - Aldicarb (2-methyl-2(methylthio) propanal o-[(methylamino)-carbonyl] oxime) is a
      pesticide manufactured since 1965. This carbamate ester is sold under the
      tradename, Temik, and is used as insecticide and nematicide. The Environmental
      Protection Agency has classified aldicarb in the highest toxicity category and
      has defined a strict control for its delivery and use. In Brazil and the
      Caribbean island, aldicarb is illegally used as a household rodenticide with a
      widespread risk of poisoning. Our study presents the first review of aldicarb
      poisoning circumstances associated with clinical and analytical findings.
      Moreover, the oxime treatment is discussed. Eighteen patients with cholinergic
      symptoms admitted to the Emergency Unit and two deceased with a history of
      aldicarb poisoning were included in the study. As agricultural workers, only two
      of them could legally use Temik. Seventy percent of the patients was managed by
      the Emergency Mobil Unit. Serum cholinesterase activity was always lower than 30%
      of the normal range and aldicarb was identified by UV spectra and retention time
      after liquid chromatography separation. The most common muscarinic effect was
      diarrhea, the main nicotinic sign fasciculation and almost half of the poisoned
      patients had central nervous system (CNS) depression (Glasgow Coma Score lower
      than 8). Four patients had serious conduction abnormalities and two of them died.
      These results suggest that aldicarb intoxication is always severe. Oxime
      treatment did not produce side effects and should be recommended whenever the
      pesticide involved is unknown. Effective measures should be implemented to stamp
      out the illicit use of aldicarb.

PMID- 11291737
TI  - Triage for Leiurus quinquestriatus scorpion envenomation in children--is routine
      ICU hospitalization necessary?
AB  - (1) Leiurus quinquestriatus scorpion (LQS) envenomation is a common public health
      problem with a similar clinical presentation in the Middle East and worldwide:
      localized reactions occur in up to 97% of the victims. (2) LQS envenomation in
      children is potentially fatal since the severity of symptoms is weight-dependent.
      (3) A common policy is to hospitalize all children stung by the LQS-regardless of
      clinical severity-in the pediatric intensive care unit (PICU). (4) Seventeen of
      18 children treated at two Israeli medical centers during an 8-year period
      developed mild to moderate clinical manifestations (antivenin was given in the
      one severe case; all children survived): all 18 had been transferred to an ICU
      for surveillance. Since patient care in PICUs is far more costly and manpower
      intense than in general emergency rooms, we propose that a protocol of 6 h of
      surveillance in the emergency department is adequate and safe for most children
      who had been stung by LQS. Only children who develop systemic manifestations
      should be hospitalized and transferred to the intensive care unit. (5) Further
      prospective studies should be conducted to define specific subgroups that may
      benefit from these recommendations.

PMID- 11291738
TI  - Lack of effects of hydrocortisone pretreatment on zinc-induced changes in protein
      assemble.
AB  - Inhalational zinc intoxication may lead to the development of acute respiratory
      distress syndrome (ARDS). Pharmacological treatment of ARDS is based on
      glucocorticoids, while the efficiency of glucocorticoid treatment is discussed
      controversially. Glucocorticoid pretreatment of lung cell lines is known to cause
      disparate effects with regard to zinc susceptibility. Both substances are known
      to each interact with protein metabolism. In the present study, zinc effects were
      examined on hydrocortisone (HC)-pretreated lung cell lines by detection of
      content and synthesis of different proteins after two-dimensional (2D) gel
      electrophoresis. (1) In HC- pretreated fibroblast-like 11Lu and alveolar
      epithelial L2 cells, no zinc-mediated changes after silver staining of 2D gels
      were seen. Few differences occurred in HC-pretreated alveolar epithelial A549
      cells that might be explained by the appearance of heat shock proteins (hsp)
      after zinc exposure. (2) In autoradiographs after 35S-Met incorporation only in
      11Lu cells, small differences occurred after HC treatment as compared to controls
      without HC. (3) All cell lines tested demonstrated the same zinc-mediated changes
      in autoradiographs with a nearly complete loss of synthesized proteins and an
      appearance of a few new spots. These changes were reversible in all cell lines
      after washing out of external zinc. The new spots were transiently expressed for
      a few hours after zinc exposure. (4) The overall effect of HC pretreatment was
      rather unimpressive. The virtual lack of major effects does not support the
      hypothesis that a gross interaction between glucocorticoids and zinc at the
      cellular protein synthesis level would be an important mechanism of influence in
      zinc-induced lung injury.

PMID- 11291739
TI  - Developmental toxicity of dimethylacetamide in rabbits following inhalation
      exposure.
AB  - (1) Dimethylacetamide was tested for developmental toxicity after inhalation
      exposure of pregnant Himalayan rabbits. Fifteen female rabbits per main group
      were exposed to dimethylacetamide vapours at concentrations of 0, 0.2, 0.7 or 2.0
      mg/l (equivalent to 0, 57, 199.5 or 570 ppm) and five female rabbits per
      satellite group to 0 or 2.0 mg/l 6 h/day from day 7 post-insemination (p.i.) to
      day 19 p.i. All animals were observed until day 29 p.i. (2) No signs of maternal
      toxicity were seen in the does of the main groups (body weight and gross
      pathology) or in the does of the satellite groups (body weight, blood chemistry,
      histopathological findings of the liver). (3) Fetotoxic effects were caused at a
      concentration of 0.7 mg/l (e.g., increased skeletal variations) and 2.0 mg/l
      (e.g., significantly decreased fetal and placental weights, increase in soft
      tissue and skeletal variations). At 2.0 mg/l, there were also signs of a weak
      teratogenic effect expressed as a marginal, statistically not significant
      increase in soft tissue malformations (regarding the heart and great vessels). No
      compound-related effects were observed in the fetuses after exposure to 0.2 mg/l.
      (4) The highest concentration tested under these conditions (2.0 mg/l) was found
      to be a no-observable-adverse-effect-level (NOAEL) for the maternal Himalayan
      rabbit, whereas 0.2 mg/l was defined as the NOAEL for the developing organism.

PMID- 11291740
TI  - Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered
      intracerebrally in rats.
AB  - Brain tumors are often incurable despite current aggressive treatment modalities.
      Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can
      maximize the radioisotope and Mab concentration to tumor sites while reducing
      systemic toxicity. h-R3 is a humanized antiepidermal growth factor receptor Mab
      that successfully targets the epidermal growth factor receptor, which is
      overexpressed in glioblastomas. We studied the acute local and systemic toxicity
      effects of intraventricular 188Re-h-R3 in rats. Forty rats were distributed into
      four groups with five animals of each sex in each group. A single 5 -microl dose
      (2.5 microl into the left and 2.5 microl into the right lateral ventricles) of
      neutral solution containing 50 microg of h- R3 labeled with 49.5 +/- 1.7,284 +/-
      13.7 or 579 +/- 23.7 muCi of 188Re were stereotactically administered to each
      animal. Control animals received vehicle alone. Each animal was observed twice
      daily for detection of toxicity signs. Body weights were recorded on days 0, 7
      and 14. Blood samples for analysis of hematological and clinical chemistry
      parameters were taken on days 0 and 14. Necropsy and histopathological studies
      were carried out after completion of the study. All animals, but one, remained
      clinically stable. Toxicities included local radionecrosis, discrete increase in
      ALAT and creatinine blood values at higher dose level. We concluded that a single
      intraventricular administration of relatively large doses of 188Re-h-R3 is
      tolerable and causes minimal local and systemic toxicity effects in rats.
      Nevertheless, further studies are necessary to discard learning and behavioral
      problems.

PMID- 11291741
TI  - Evaluation of cot mattress inner foam as a potential site for microbial
      generation of toxic gases.
AB  - Recent reports of biovolatilisation of phosphorus and antimony by anaerobic
      bacteria and of leaching of phosphorus and antimony fire-retardant additives from
      PVC cot mattress covers, indicate that the polyurethane inner-foam of cot
      mattresses could be a site for generation of toxic gases of group 15 elements. A
      toxic gas hypothesis for sudden infant death syndrome (SIDS) involving
      polyurethane foam of cot mattresses was proposed and tested experimentally.
      Levels of antimony, phosphorus, arsenic and bismuth were determined at four sites
      for 44 SIDS and 50 control (no death) cot mattress foams. There was no evidence
      to suggest that the levels of these elements in cot mattress foam have a causal
      relation to SIDS. Leaching of antimony trioxide from PVC mattress covers could
      account for detectable levels of this element in 52% of the cot mattress samples
      analysed. Volatile forms of antimony, phosphorus, arsenic and bismuth was not
      detected in the headspace of mixed or monoseptic cultures of anaerobic bacteria
      containing polyurethane foam. Past microbial activity had given rise to
      involatile methylated species of antimony in some of the cot mattress foams
      tested (61%, n = 24). Abiotic oxidation of biogenic trimethylantimony together
      with physical adsorption of methylantimony forms to the polyurethane foam matrix
      could account for the apparent absence of "escaped" volatile antimony species in
      culture headspaces of incubation vial. There was no evidence to suggest that
      levels of trimethylantimony or total methylantimony forms in cot mattress foams
      have a causal relation to SIDS.

PMID- 11291742
TI  - Detecting hormesis using a non-parametric rank test.
AB  - When a dose-response experiment is conducted, the enhanced responses can be
      observed at low doses. This phenomenon is often called hormesis. The enhanced
      responses at low doses does not necessarily mean the existence of hormesis. It is
      important to conduct statistical analyses to determine whether a departure from
      monotonic relationships is significantly different from the chance occurrence.
      This paper introduces a non-parametric rank test to detect hormesis. To
      illustrate the use of this method, we apply it to the data from a Whole Effluent
      Toxicity test. We demonstrate that the occurrence of hormesis can be
      statistically evaluated by using this non-parametric rank test.

PMID- 11291743
TI  - Overcoming antimicrobial resistance by targeting resistance mechanisms.
AB  - Three mechanisms of antimicrobial resistance predominate in bacteria: antibiotic
      inactivation, target site modification, and altered uptake by way of restricted
      entry and/or enhanced efflux. Many of these involve enzymes or transport proteins
      whose activity can be targeted directly in an attemptto compromise resistance
      and, thus, potentiate antimicrobial activity. Alternatively, novel agents
      unaffected by these resistance mechanisms can be developed. Given the ongoing
      challenge posed by antimicrobial resistance in bacteria, targeting resistance in
      this way may be our best hope at prolonging the antibiotic era.

PMID- 11291744
TI  - A novel and simple type of liposome carrier for recombinant interleukin-2.
AB  - The strong interaction between recombinant interleukin-2 (IL-2) and liposome was
      characterized and its possible application to drug-delivery control considered.
      The liposomes were prepared with egg phosphatidylcholine, distearoyl
      phosphatidylglycerol (DSPG), dipalmitoyl-phosphatidylcholine, dipalmitoyl
      phosphatidylglycerol or distearoyl-phosphatidylcholine (DSPC). Small and
      hydrophobic liposomes were selected, which were composed of saturated and long
      fatty-acid-chain phospholipids. When the composition and the mixture ratio of IL
      2 and the liposomewere optimized, morethan 95% ofthe lyophilized IL-2 (Imunace,
      350000 JRU) was adsorbed consistently onto the DSPC-DSPG liposome (molar ratio,
      10:1; 25 micromol mL(-1); 30 nm in size). Merely mixing IL-2 lyophilized with
      liposome suspension is convenient pharmaceutically. After intravenous
      administration to mice, liposomal IL-2 was eliminated half as slowly from the
      systemic circulation as free IL-2, with more than 13 and 18 times more IL-2 being
      delivered to the liver and spleen, respectively. After subcutaneous
      administration of liposomal IL-2 to mice, the mean residence time of IL-2 in the
      systemic circulation was 8 times that of free IL-2. These results show that IL-2
      consistently adsorbs onto the surface of liposomes after optimization of its
      composition and mixing ratio. Intravenous and subcutaneous administration to mice
      demonstrates the gradual release of IL-2. Further trials are warranted using
      these liposomes.

PMID- 11291746
TI  - Distribution of the methylpiperazinopyridobenzoxazepine derivative JL13, a
      potential antipsychotic, in rat brain.
AB  - The brain uptake and distribution of the potential antipsychotic 5-(4
      methylpiperazin-1-yl)-8-chloro-pyrido[2,3][1,5]benzoxazepine fumarate (JL13) was
      examined in rats after neuropharmacologically active doses. Plasma and brain
      concentrations of the compound were measured by reversed-phase HPLC with UV
      detection (210 nm). Clozapine was used as an internal standard. After an
      intraperitoneal dose of 10 mg kg(-1), the compound attained mean maximum plasma
      concentrations within 5 min of dosing, then declined with a mean elimination half
      life of approximately 1 h. It rapidly crossed the blood-brain barrier and
      equilibrated with plasma, achieving mean maximum concentrations and area under
      the curve approximately 20-times those in plasma, with slight regional
      differences. Disappearance from whole brain almost paralleled its disappearance
      from plasma. There was a linear relationship between JL13 concentrations in
      plasma and brain regions, and in all tissues the concentrations of the compound
      increased almost linearly with the dose over the range of 5-20 mg kg(-1). It thus
      appears that JL13 brain pharmacokinetics parallels that in plasma, and that
      plasma concentrations accurately predict brain concentrations in rats.

PMID- 11291745
TI  - Characterization of glass solutions of poorly water-soluble drugs produced by
      melt extrusion with hydrophilic amorphous polymers.
AB  - Indomethacin, lacidipine, nifedipine and tolbutamide are poorly soluble in water
      and may show dissolution-related low oral bioavailability. This study describes
      the formulation and characterization of these drugs as glass solutions with the
      amorphous polymers polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone-co-vinyl
      acetate by melt extrusion. The extrudates were compared with physical mixtures of
      drug and polymer. X-ray powder diffraction, thermal analysis, infrared
      spectroscopy, scanning electron microscopy, HPLC, moisture analysis and
      dissolution were used to examine the physicochemical properties and chemical
      stability of the glass solutions prepared by melt extrusion at a 1:1 drug/polymer
      ratio. Depending on the temperature used, melt extrusion produced amorphous glass
      solutions, with markedly improved dissolution rates compared with crystalline
      drug. A significant physico-chemical interaction between drug and polymer was
      found for all extrudates. This interaction was caused by hydrogen bonding (H
      bonding) between the carbonyl group of the pyrrole ring of the polymer and a H
      donor group of the drug. Indomethacin also showed evidence of H-bonding when
      physical mixtures of amorphous drug and PVP were prepared. After storage of the
      extrudates for 4-8 weeks at 25 degrees C/75% relative humidity (RH) only
      indomethacin/polymer (1:1) extrudate remained totally amorphous. All extrudates
      remained amorphous when stored at 25 degrees C/< 10% RH. Differences in the
      physical stability of drug/polymer extrudates may be due to differences in H
      bonding between the components.

PMID- 11291747
TI  - Control of impurities in diphenhydramine hydrochloride by an ion-pairing, reverse
      liquid chromatography method.
AB  - A precise, sensitive, repeatable and robust reverse-phase liquid chromatographic
      method has been developed for the control of seven possible impurities of
      diphenhydramine hydrochloride. The robustness of the method was examined by
      varying, in turn, each of four mobile-phase parameters (acetonitrile content,
      buffer salt concentration, ion-pair reagent concentration and pH). The method was
      linear in the range 0-0.14 mg mL(-1) for diphenhydramine hydrochloride with an
      acceptable precision and accuracy, and a limit of detection of 0.17 microg mL(
      1). Five samples of diphenhydramine hydrochloride from two sources were analysed
      with the developed liquid chromatographic method.

PMID- 11291748
TI  - A study of the anti-invasive properties of N-alpha-phthalimidomethyl
      ketomethylene tripeptide-based metalloprotease inhibitors.
AB  - We have developed matrix metalloprotease (MMP) inhibitors based on synthetic
      peptides incorporating a non-cleavable peptide-bond isostere at the site of the
      putative scissile bond. These inhibitors, N-alpha-phthaloyl-Gly-psi(CO-CH2)-Leu
      Tyr-Ala-NH2 (Pht-G-CH2-LYA-NH2) and N-alpha-phthaloyl-Gly-psi(CO-CH2)-Leu-Tic-Ala
      NH2 (Pht-G-CH2-LTcA-NH2) were kinetically evaluated against the type IV
      collagenases, gelatinase A (MMP-2) and B (MMP-9), and compared with an exactly
      analogous chelating-based inhibitor, N-alpha-mercaptoacetyl-Leu-Tyr-Ala-NH2
      (HSCH2CO-LYA-NH2). The peptide inhibitors were also tested for their anti
      invasive effects on breast carcinoma cell lines using a modification of the
      Boyden chamber assay. Gelatin zymography was utilized to identify gelatinolytic
      activities present in media removed from cultured breast cancer cells. Of the two
      N-alpha-phthalimidomethyl-ketomethylene peptide-based inhibitors, Pht-G-CH2-LYA
      NH2 proved the more effective inhibitor of MMP-2 and MMP-9 (Ki 34.27 and 45.75
      microM, respectively). However, when tested against two breast cancer cell lines,
      T47D and MDA-MB-231, both inhibitors were able to effectively reduce tumour cell
      invasion through a type IV collagen matrix by up to 91.2%. Of particular interest
      was the observation that Pht-G-CH2-LYA-NH2 was the most potent inhibitor of
      invasion by the highly aggressive MDA-MB-231 cells, despite the cells' relative
      lack of active secreted metalloprotease activity. The results obtained from this
      kinetic and anti-invasive analysis of the new inhibitors suggest that compounds
      incorporating the N-alpha-phthalimidomethyl-ketomethylene peptide-bond isostere
      may have potential for development as new agents with anti-metastatic properties.

PMID- 11291749
TI  - Synthesis and hydrolytic behaviour of glycerol-1,2-diibuprofenate-3-nitrate, a
      putative pro-drug of ibuprofen and glycerol-1-nitrate.
AB  - Nitroxylated derivatives of non-steroidal anti-inflammatory drugs appear to offer
      protection against the gastrotoxicity normally associated with non-steroidal anti
      inflammatory drugs, ostensibly via local production of nitric oxide. A diester of
      ibuprofen and glycerol-1-mononitrate has been prepared via the condensation of
      ibuprofen with 3-bromopropan-1,2-diol, followed by silver-(I)-nitrate-mediated
      nitroxylation. The release of ibuprofen from this diester has been studied in a
      simulated gastric fluid model with direct analysis by reverse-phase HPLC, using
      an acetonitrile-water (80%:20%) mobile phase containing trifluoroacetic acid
      (0.005%). n-Propyl ibuprofen was found to undergo pH-dependent hydrolysis,
      ranging from negligible hydrolysis at pH 5 to 52% hydrolysis at pH 3, over a 2-h
      period in this model. The ibuprofen-glycerol mononitrate diester was subjected to
      the most vigorous model hydrolytic conditions and was found to undergo 50 %
      hydrolysis during the study period. This study shows that pro-drugs of ibuprofen
      and glycerol mononitrate can be obtained, and can undergo degradation to the
      parent drugs under conditions simulating those likely to be encountered in the
      stomach.

PMID- 11291750
TI  - Clonidine-induced antinociception and locomotor hypoactivity are reduced by
      dexamethasone in mice.
AB  - The effects of dexamethasone pretreatment on clonidine-induced antinociception
      and locomotor hypoactivity were investigated in mice. In the hot-plate and the
      tail-flick tests, dexamethasone administered intraperitoneally at a dose of 1 mg
      kg(-1), 30 or 60 min before clonidine, reduced clonidine antinociception in both
      tests and reduced clonidine-induced locomotor hypoactivity in the activity cage.
      When administered 15 min before clonidine, dexamethasone had no effect on
      clonidine antinociception. A higher dexamethasone dose (10 mg kg(-1)) induced the
      same effects observed at a dose of 1 mg kg(-1) in the hot-plate and the tail
      flick tests, but the former dose had a stronger effect on locomotor hypoactivity.
      Dexamethasone (10 ng/mouse) administered intracerebroventricularly 30 min before
      clonidine was also able to reduce both clonidine-induced antinociception and
      locomotor hypoactivity. The protein synthesis inhibitor, cycloheximide,
      administered intraperitoneally at the dose of 10 mg kg(-1), 2 h before clonidine,
      was able to prevent dexamethasone effects on clonidine-induced antinociception.
      The glucocorticoid receptor antagonist RU-38486, administered
      intracerebroventricularly at the dose of 1 ng/mouse, was also able to block
      dexamethasone effects on clonidine-induced antinociception and locomotor
      hypoactivity, whereas both cycloheximide and RU-38486 per se did not influence
      pain sensitivity or locomotor activity. These results suggest that the
      dexamethasone effects on clonidine-induced antinociception and locomotor
      hypoactivity depend on the stimulating effects that dexamethasone exert, on the
      protein synthesis via the glucocorticoid receptor in the brain.

PMID- 11291751
TI  - The development and in-vitro evaluation of novel mixed metal hydroxy-carbonate
      compounds as phosphate binders.
AB  - The currently available phosphate binders are relatively inefficient and suffer
      from clinical side-effects of increased absorption of calcium and aluminium and
      the diarrhoea-inducing effects of magnesium. A new class of compounds based on
      mixed metal hydroxides has been developed and evaluated for their potential as
      phosphate binders. The mixed metal hydroxides were prepared using a standard
      procedure for hydrotalcite (Al2Mg6(OH)16.CO3.4H2O) by substituting Fe3+ for Al3+,
      with Mg2+ or Ca2+ as the divalent metal ion. Phosphate precipitation (binding)
      was examined at different pH values in aqueous solution and in various food
      mixtures in comparison with hydrotalcite, Al(OH)3, CaCO3 and Mg(OH)2 on the same
      weight-to-weight basis. A series of compounds with differing ratios of metal ions
      (Fe:Mg/Ca 1:2 or 1:3) gave analytically similar ratios to those predicted from
      the initial amounts added. CTFeCa bound > 90% phosphate in aqueous solution
      compared with 65% binding with CTFeMg, 85% binding with Mg(OH)2, and less than
      30% binding for CaCO3 and Al(OH)3. The mixed metal compounds also bound up to 80%
      phosphate in various food matrices, which was relatively independent of changes
      in pH, compared with Mg(OH)2, where binding decreased from 85% at pH 3.0 to 25%
      at pH 8.0. Al(OH)3 and CaCO3 were relatively ineffective phosphate binders under
      all the conditions tested. The mixed metal hydroxides compounds show considerable
      promise as phosphate binders over those currently available and warrant further
      patient-based in-vivo testing.

PMID- 11291752
TI  - Acetylcholine induces cytosolic Ca2+ mobilization in isolated distal colonic
      crypts from normal and cystic fibrosis mice.
AB  - In intestinal biopsies from cystic fibrosis (CF) patients acetylcholine fails to
      elicit a chloride secretion response, and this observation can be explained by a
      defect in the Ca2+ signalling pathway in CF secretory cells. We tested the
      hypothesis that in CF intestine, the generation of an intracellular Ca2+ signal
      upon cholinergic stimulation is absent. A transgenic CF mouse model was used.
      Electrical measurements on intact jejunum and unstripped colon were performed in
      Ussing chambers. Intact distal colonic crypts were isolated, and the
      intracellular Ca2+ concentration was monitored using the Ca2+-sensitive dye fura
      2. Acetylcholine increased the short-circuit current generated by wild-type
      jejunum and colon, but failed to induce a response in CF tissues. Acetylcholine
      caused a transient elevation in the intracellular Ca2+ concentration in colonic
      crypts from both wild-type and CF mice; the amplitude and timing of the response
      in CF crypts was indistinguishable from that in wild-type crypts. The response to
      acetylcholine was also observed in the absence of extracellular calcium,
      indicating intracellular stores as the source from which the cytosolic Ca2+
      concentration increased. We conclude that the absence of a cholinergically
      induced secretory response in CF intestine is not due to a defect in the
      generation of a Ca2+ signal in intestinal cells upon cholinergic stimulation.

PMID- 11291753
TI  - Cellular characterization of an in-vitro cell culture model of seal-induced
      cardiac ischaemia.
AB  - The lack of a well-characterized in-vitro cell culture model of load-induced
      cardiac ischaemia has hampered investigations into the mechanism of ischemic
      injury. We therefore developed a new in-vitro model of cardiac ischaemia that
      mimics distinct features of ischaemic injury. Neonatal rat heart cells were
      cultured in a sealed flask for 24-72 h. In this environment, the cells were
      exposed to stresses of hypoxia, acidosis and stagnant incubation medium. The pO2
      and pH of the medium gradually decreased during the ischaemic insult and
      ultimately fell to a level of 14 mmHg and pH 6.8, respectively. The model
      triggered severe cell injury, including morphological degeneration, CPK release,
      beating impairment and ATP depletion. Apoptosis occurred in some cardiomyocytes
      as early as 24 h after onset of seal-induced ischaemia. This was evidenced by
      positive nuclear staining using Hoechst 33258 and by the induction of caspase-3
      mRNA. By 72 h, internucleosomal DNA fragmentation was observed in 45% of the
      myocytes; however, a non-myocyte preparation subjected to the same ischaemic
      insult exhibited no evidence of DNA fragmentation. These results demonstrate that
      neonatal cardiomyocytes subjected to the new simulated ischaemia model exhibit
      several similarities to cardiac ischaemia, including the simultaneous appearance
      of necrosis, breakdown of cellular ATP, beating cessation and apoptosis. The new
      model should prove useful in unravelling the molecular alterations underlying
      ischaemic injury and myocardial apoptosis.

PMID- 11291754
TI  - Prevention of neuronal cell damage induced by oxidative stress in-vitro: effect
      of different Ginkgo biloba extracts.
AB  - The effect of two different Ginkgo biloba extracts (GB1 and GB4) was studied in
      vitro on cultured neurons exposed to oxidative stress caused by H2O2(50 micromol
      L(-1)) and FeSO4(100 micromol L(-1)). Only about 50% of the neurons were still
      viable at the end of the experiment (8 h) in control conditions, while the two
      extracts dose dependently increased the number of viable cells, in the
      concentration range 10-200 microg mL(-1). The two Ginkgo biloba extracts differed
      in their effect on hydroxyl-radical-scavenging capacity: GB1 and GB4 had an IC50
      (50% inhibiting concentration) value of 78 microg mL(-1) and 186 microg mL(-1),
      respectively. However, both extracts inhibited apoptosis in cortical neurons
      after oxidative stress in-vitro. These observations make one suppose that
      different preparations of Ginkgo biloba have quantitatively different actions and
      outline the importance of the contribution of apoptosis prevention toward their
      neuroprotective action.

PMID- 11291755
TI  - The effects of freeze-drying on the stability of liposomes to jet nebulization.
AB  - Egg phosphatidylcholine liposomes were freeze-dried in the presence and absence
      of trehalose. The lyophilized liposomes were rehydrated and aerosolized using a
      Pari LC jet nebulizer. The size of the aerosols generated was determined by laser
      diffraction, which was also used to determine the size distribution of the
      liposomes before lyophilization, post-rehydration, in the nebulizer post
      aerosolization and those deposited in the two stages of a twin impinger. In the
      absence of trehalose, large liposomes and vesicle aggregates were produced on
      rehydration, which were rapidly reduced in size on nebulization. Liposomes with a
      mean size of 1 or 2.5 microm, freeze-dried with trehalose, had a mean size less
      than 3 microm following rehydration and exhibited enhanced stability to
      nebulization. Liposomes of 1 microm before freeze-drying were evenly distributed
      within aerosols generated by the nebulizer, whilst aerosols generated from 2.5
      microm liposomes were fractionated in the twin impinger with the largest
      liposomes collected in the upper stage.

PMID- 11291756
TI  - The urinary excretion of gamma-hydroxybutyric acid in man.
AB  - gamma-Hydroxybutyric acid (GHB) has been widely associated with drug-facilitated
      sexual assault (DFSA). However, its excretion profile in man has not been well
      characterized. To assess the detectability of GHB for forensic cases and to
      correlate urinary levels with dose, we have examined the excretion profiles of 1-
      and 2-g doses of GHB (sodium salt) in a healthy male volunteer. The urinary
      levels were measured by a novel, simple and highly reproducible method. The drug
      was found to be excreted in small amounts in the free form (0.86 and 1.16% for 1-
      and 2-g doses, respectively) rapidly in urine (< or = 10 h). The urinary levels
      were found to be in the low mg L(-1) range (up to 29.1 mg L(-1)). The work
      presented demonstrates that it is of the utmost importance to collect the samples
      as soon as possible following the alleged assault.

PMID- 11291757
TI  - Formation of a defluorinated metabolite of a quinoxaline antiviral drug catalysed
      by human cytochrome P450 1A2.
AB  - The in-vitro metabolism of GW420867X ((S)-2-ethyl-7-fluoro-3-oxo-3, 4-dihydro-2H
      quinoxaline-1-carboxylic acid isopropyl ester), a quinoxaline drug for the
      potential treatment of HIV, has been studied with singly expressed human
      cytochromes P450 (CYP 450). No biotransformation of [14C]GW420867X was evident in
      the presence of any of the CYP 450 isoforms, with the exception of CYP 450 1A2,
      where a single metabolite was observed in the HPLC radiochromatograms of enzyme
      incubations with the test compound. The structure of this metabolite was
      determined by nuclear magnetic resonance spectroscopy and mass spectrometry, and
      was shown to correspond to the replacement of the aromatic fluorine of GW420867X
      with a hydroxyl group. Thus, it appeared that CYP 450 1A2 catalysed the specific
      defluorination of GW420867X, presumably during formation of an arene oxide
      intermediate during aromatic hydroxylation.

PMID- 11291758
TI  - Effect of indinavir on the pharmacokinetics of rifampicin in HIV-infected
      patients.
AB  - Indinavir, an antiretroviral agent, has an influence on the pharmacokinetics of
      other drugs by acting as an inhibitor of cytochrome P450-mediated drug
      metabolism. The incidence of tuberculosis has increased dramatically in the past
      decade because of an epidemic of HIV infection. Rifampicin is still one of the
      most valuable drugs for the standard treatment of tuberculosis. The objective of
      this study was to investigate the effects of indinavir on the pharmacokinetics of
      rifampicin in man. Our study was conducted in eleven HIV-infected patients. All
      patients received a 600-mg single dose of oral rifampicin on day 1 and 15- and
      800-mg oral indinavir three times a day from day 2 to day 15. Rifampicin
      pharmacokinetic studies were carried out on day 1 and day 15. The results showed
      that rifampicin concentrations were higher when it was administered with
      indinavir than when it was administered alone. With concomitant indinavir
      medication, the mean AUC0-24 of rifampicin was increased by 73%. Therefore, we
      conclude that indinavir has an inhibitory effect on the metabolism of rifampicin.

PMID- 11291759
TI  - A rapid and sensitive method for the determination of the amount of theophylline
      in blood spots.
AB  - Monitoring of drugs (such as theophylline) with a narrow therapeutic window could
      be simplified if patients were able to submit blood spots for analysis. This
      could reduce clinic attendance for venous blood sampling and save staff time. A
      rapid sensitive method utilizing liquid chromatography-mass spectrometry has been
      developed to determine the amount of theophylline in blood spots. The lowest
      level of theophylline analysed in a blood spot was 15 ng extracted into 250
      microL and this was still considerably above the limit of quantification (3 ng in
      250 microL). The levels of theophylline in blood spots correlated well with
      theophylline levels in plasma samples obtained from the same patients. The assay
      might be of use in therapeutic drug monitoring of theophylline and blood spot
      sampling could be applied to other drugs where therapeutic monitoring is
      required.

PMID- 11291760
TI  - Synthesis of N-pyridinyl(methyl)-1,2-dihydro-4-hydroxy-2-oxoquinoline-3
      carboxamides and analogues and their anti-inflammatory activity in mice and rats.
AB  - The topical anti-inflammatory activity of a series of N-pyridinyl(methyl)1,2
      dihydro-4-hydroxy-2-oxoquinoline-3-carboxamides, analogues of roquinimex, has
      been evaluated by measuring their inhibitory effect in the phorbol myristate
      acetate (PMA)-induced mouse ear swelling test, used as a screening test. All the
      eight carboxamides tested (9-16) exhibited significant inhibitory activity at 0.4
      and 0.2 mM kg(-1). The most potent compound, the 6-bromo derivative 12, induced a
      73% inhibition at 0.2 mM kg(-1). Pharmacomodulation was carried out by
      heterocycle opening and molecular simplification leading to
      pentafluorobenzoylacetamide 17, pentafluorocinnamamides 18 and 19, and
      pentafluorobenzaldimines 20 and 21. All the five compounds exerted a reduction in
      swelling (49-63% at 0.2 mM kg(-1)) comparable with ibuprofen (56%). Anti
      inflammatory activity of the most efficient compounds was evaluated by
      carrageenan-induced rat paw oedema inhibition. The pentafluorobenzaldimine 20
      showed the highest activity with an inhibition percentage of 85% at 0.2 mM kg(
      1).

PMID- 11291761
TI  - Sources and targets of nitric oxide signalling in insect nervous systems.
AB  - Nitric oxide (NO) is a membrane permeant signalling molecule which activates
      soluble guanylyl cyclase and leads to the formation of cyclic GMP (cGMP) in
      target cells. In the nervous system, NO/cGMP signalling is thought to play
      essential roles in synaptic plasticity during development and also in the mature
      animal. This review summarizes neurochemical, cell biological, and physiological
      investigations of NO/cGMP signalling in the nervous system of insects. The
      anatomical localization of donor and target cells suggests functions in
      olfaction, vision, and mechanosensation. Behavioural assays have uncovered
      contributions of NO signalling in oxygen sensing, habituation to chemosensory
      stimuli, and associative memory formation. During development, NO regulates cell
      proliferation, axonal outgrowth, and synaptic maturation. The cellular
      distribution of NO-responsive cells suggests that NO can serve as a retrograde
      synaptic messenger, as an intracellular messenger, and as a lateral diffusible
      messenger irrespective of conventional synaptic connectivity.

PMID- 11291762
TI  - Differences in the distribution and chemical coding between neurons in the
      inferior mesenteric ganglion supplying the colon and rectum in the pig.
AB  - The distribution and chemical coding of neurons in the porcine left and right
      inferior mesenteric ganglion projecting to the ascending colon and rectum have
      been investigated by using combined retrograde tracing and double-labelling
      immunohistochemistry. The ganglion contained many neurons supplying both gut
      regions. The colon-projecting neurons (CPN) occurred exclusively in the cranial
      part of the ganglia where they formed a large cluster distributed along the dorso
      lateral ganglionic border and a smaller cluster located close to the caudal
      colonic nerve output. The rectum-projecting neurons (RPN) formed a long stripe
      along the entire length of the lateral ganglionic border and, within the right
      ganglion only, a small cluster located close to the caudal colonic nerve output.
      Immunohistochemistry revealed that the vast majority of the CPN and RPN were
      noradrenergic (tyrosine-hydroxylase-positive). Many noradrenergic neurons
      supplying the colon contained somatostatin or, less frequently, neuropeptide Y.
      In contrast, a significant subpopulation of the noradrenergic RPN expressed
      neuropeptide Y, whereas only a small proportion contained somatostatin. A small
      number of the non-adrenergic RPN were cholinergic (choline-acetyltransferase
      positive) and a much larger subpopulation of the nerve cells supplying both the
      colon and rectum were non-adrenergic and non-cholinergic. Many cholinergic
      neurons contained neuropeptide Y. The non-adrenergic non-cholinergic neurons
      expressed mostly somatostatin or neuropeptide Y and some of those projecting to
      the rectum contained nitric oxide synthase, galanin or vasoactive intestinal
      polypeptide. Many of both the CPN and RPN were supplied with varicose nerve
      fibres exhibiting immunoreactivity against Leu5-enkephalin, somatostatin, choline
      acetyltransferase, vasoactive intestinal polypeptide or nitric oxide synthase The
      somatotopic and neurochemical organization of this relatively large population of
      differently coded inferior mesenteric ganglion neurons projecting to the large
      bowel indicates that these cells are probably involved in intestino-intestinal
      reflexes controlling peristaltic and secretory activities.

PMID- 11291763
TI  - Granule cell raphes in the developing mouse cerebellum.
AB  - The cerebellar cortex of many vertebrates shows a striking parasagittal
      compartmentation that is thought to play a role in the establishment and
      maintenance of functional cerebellar connectivity. Here, we demonstrate the
      existence of multiple parasagittal raphes of cells in the molecular layer of the
      developing cerebellar cortex of postnatal mouse. The histological appearance and
      immunostaining profile of the raphe cells suggest that they are migrating granule
      cells. We therefore conclude that the granule cell raphes previously described in
      birds also exist in a mammalian species. The raphes in mouse are visible on
      nuclear stains from around birth to postnatal day 6 and are frequently found at
      the boundaries of Purkinje cell segments that differentially express cadherins
      ("early-onset" parasagittal banding pattern). A similar relation between the
      raphe pattern and various markers for the early-onset banding pattern has been
      found in the chicken cerebellum. One of the cadherins mapped in the present study
      (OL-protocadherin) continues to be expressed in specific Purkinje cell segments
      until at least postnatal day 14. At this stage of development, the borders of the
      OL-protocadherin-positive Purkinje cell segments coincide with the borders of
      Purkinje cell segments that express zebrin II, a marker for the "late-onset"
      parasagittal banding pattern which persists in the adult cerebellum. These
      findings demonstrate that the early-onset banding pattern, as reflected in the
      complementary arrangement of raphes/Purkinje cell segments, and the late-onset
      pattern of zebrin II expression share at least some positional cues during
      development.

PMID- 11291764
TI  - Localization of the Wilm's tumour protein WT1 in avian embryos.
AB  - The Wilms' tumour suppressor gene WT1 encodes a zinc-finger transcription factor
      which is essential for the development of kidney, gonads, spleen and adrenals.
      WT1-null embryos lack all of these viscerae and they also show a thin ventricular
      myocardium and unexpectedly die from cardiac failure between 13 and 15 days post
      coitum. We studied the localization of the WT1 protein in chick and quail embryos
      between stages HH18 and HH35. In early embryos, WT1 protein was located in
      specific areas of the coelomic mesothelium adjacent to the nephric ducts, the
      myocardium or the primordia of the endodermal organs (gut, liver and lungs).
      These mesothelial areas also showed localized expression of Slug, a zinc-finger
      transcription factor involved in epithelial-mesenchymal transitions. WT1+
      mesenchymal cells were always found below the immunoreactive mesothelial areas,
      either forming a narrow band on the surface of the endodermal organs (gut, liver
      and lungs) or migrating throughout the mesodermal organs (mesonephros,
      metanephros, gonads, spleen and heart). In the developing heart, the invasion of
      WTI+ cells started at stage HH26, and all the ventricular myocardium was pervaded
      by these cells, presumably derived from the epicardium, at HH30. We suggest that
      WT1 is not required for the epithelial-mesenchymal transition of the coelomic
      mesothelium, but it might be a marker of the mesothelial-derived cells, where
      this protein would be acting as a repressor of the differentiation.

PMID- 11291765
TI  - Thyroid-hormone-dependent and fibroblast-specific expression of BMP-4 correlates
      with adult epithelial development during amphibian intestinal remodeling.
AB  - We have identified one of the genes that are up-regulated by thyroid hormone (TH)
      in Xenopus laevis small intestine as the Xenopus homolog of bone morphogenetic
      protein-4 (BMP-4). To clarify possible roles of BMP-4 in intestinal remodeling
      during metamorphosis, we have examined its expression in X. laevis intestine by
      using in situ hybridization and organ culture techniques. At the beginning of
      metamorphic climax, BMP-4 mRNA first becomes detectable in the connective tissue,
      concurrently with the appearance of adult epithelial primordia. Subsequently,
      when the adult epithelial primordia are actively proliferating, BMP-4 mRNA
      becomes more abundant only in the connective tissue with a gradient toward the
      epithelium. Thereafter, as the adult primordia differentiate, the level of BMP-4
      mRNA gradually decreases. Thus, BMP-4 expression correlates well with cell
      proliferation and/or initial differentiation of the adult epithelium, but not
      with apoptosis of the larval epithelium. Furthermore, the present culture study
      indicates that (1) TH-induced expression of BMP-4 mRNA is higher in the anterior
      part of the intestine than in the posterior part, which agrees with the better
      development of the adult epithelium in the more anterior part, and that (2) the
      expression of BMP-4 mRNA is up-regulated by TH in the presence of epithelium, but
      not in its absence. Therefore, BMP-4, which is indirectly induced by TH through
      some epithelial factor(s), probably plays important roles in adult epithelial
      development during amphibian intestinal remodeling.

PMID- 11291766
TI  - Intracellular vesicular trafficking in the gill epithelium of urea-excreting
      fish.
AB  - Most teleost fish are ammoniotelic, and relatively few are ureotelic, in which
      the majority of nitrogenous waste is excreted as urea. This study aimed to
      determine whether the gill ultrastructure of ureotelic fish might have specific,
      unique characteristics compared with ammoniotelic fish. The gill morphology was
      studied in three closely related species of the family Batrachoididae: Opsanus
      beta, the gulf toadfish; Opsanus tau, the oyster toadfish; and Porichthys
      notatus, the plainfin midshipman, because prior studies have demonstrated that
      the two former species are ureotelic and excrete urea in unique, short daily
      pulses, whereas the latter is ammoniotelic. Ultrastructural studies demonstrated
      significant trafficking of dense-cored vesicles (50-200 nm) between the Golgi
      apparatus and the apical membrane of epithelial cells surrounding gill filaments
      and lamellae in these two Opsanus spp. The material constituting the core of
      these vesicles was intensely stained by lead salt and was unloaded externally
      when vesicles contacted the apical membrane. Another characteristic of these urea
      secreting fish was the presence of numerous large, black-stained lysosomes, which
      contained cored vesicles, suggesting a second destination for the dense-cored
      vesicles. As a working hypothesis, the present data suggest that the urea
      transporter protein, recently found in toadfish gills, is inserted in the
      vesicle. Subsequently, it could serve to either sequester cytosolic urea that
      ultimately is secreted into the water after contact of these vesicles with the
      pavement cell apical membrane, or it could allow facilitated diffusion of urea
      across the plasma membrane following insertion into the membrane. As further
      comparative evidence, the ammoniotelic P. notatus exhibited neither the vesicular
      trafficking nor the population of lysosomes both found in Opsanus spp.

PMID- 11291767
TI  - Cysteine string proteins are associated with cortical granules of Xenopus laevis
      oocytes.
AB  - Cysteine string proteins (csps) are associated with secretory organelles in a
      wide range of eukaryotic cells. Functional studies of these proteins indicate
      that they subserve one or more vital steps in the pathway of regulated
      exocytosis. Here, we document the presence of csps in fully grown (stage VI)
      oocytes of the frog, Xenopus laevis. Both Northern and immunoblot data support
      the conclusion that csps are expressed in these cells. In addition,
      immunoreactive csp is seen even at the earliest stage of oocyte development,
      namely, in stage I oocytes. Finally, immunoblot and immunocytochemical results
      indicate that csps are associated with cortical granules of stage II-VI oocytes.
      These observations suggest that csps participate in the cortical reaction that
      underlies the sustained block to polyspermy in Xenopus eggs. Moreover, because of
      the relative ease of manipulating cells as large as Xenopus oocytes, this system
      harbors considerable promise as a model for studying the role of csps and other
      proteins in exocytotic events.

PMID- 11291768
TI  - Significance of metallothionein expression in breast myoepithelial cells.
AB  - Metallothioneins (MTs), a group of cysteine-rich proteins with a small molecular
      mass, are known to have metalloregulatory functions. MT gene expression has been
      demonstrated to be cell type-specific and differentially regulated (possibly
      related to their germ layer origin and different functional states). In vitro
      studies suggest that MT-2A, MT-IE, and MT-1F isoforms may be related to breast
      cancer. In this study, data on MT-2A, MT-1E, MT-1F mRNA analysis via reverse
      transcription-polymerase chain reaction in invasive ductal breast cancer tissues
      and their adjacent benign breast tissues from 27 mastectomies are presented.
      Expression of mRNA in all the three MT isoforms was detected in both cancerous
      and adjacent benign breast tissues (with MT-2A mRNA expression being the
      highest). MT-1F expression was significantly higher in benign breast tissues
      compared with the breast cancers (P=0.017). In situ hybridization confirmed the
      expression of MT-2A mRNA in the myoepithelial cells of the breast tissues.
      Immunohistochemical localization of the MT protein revealed that myoepithelial
      cells consistently expressed the MT protein, while the cancer cells expressed MT
      with great variation. Based on our immunohistochemical and mRNA analysis, it is
      likely that the three MT isoforms are specifically expressed in myoepithelial
      cells of benign breast tissues and cancer cells of the invasive ductal breast
      cancer tissues. As MT expression occurs in myoepithelial cells and ductal breast
      cancer cells, our finding supports the proposition that loss of myoepithelial
      cells in invasive mammary cancers may be compensated in part by changes in the
      tumor cells, which may subsequently be the basis for studying the role of MT in
      breast physiology and carcinogenesis. Differential MT-1F expression in breast
      myoepithelial cells warrants further study.

PMID- 11291769
TI  - Endothelium-independent conversion of angiotensin I by vascular smooth muscle
      cells.
AB  - The conversion of angiotensin I (AT-I) to angiotensin II (AT-II) by angiotensin I
      converting enzyme (ACE) is a key step in the action of angiotensins. ACE is
      constitutively expressed in endothelial cells, but can also be detected at low
      levels in smooth muscle cells (SMC). Furthermore, in rats the ACE activity can be
      induced in SMC in vivo by experimental hypertension or vascular injury and in
      vivo by corticoid treatment. This study was therefore undertaken to evaluate the
      conversion of AT-I and its subsequent effects in SMC in basal conditions and
      after stimulation by dexamethasone. Using rat and human SMC, showed that
      dexamethasone induced ACE expression and that this enzyme was functional, leading
      to AT-II-dependent intracellular signaling. A fourfold increase in phospholipase
      C activity in response to AT-I was observed in dexamethasone-activated SMC
      compared with quiescent SMC. This effect of dexamethasone on signal transduction
      is dependent on ACE activity, whereas AT-II receptor parameters remain unchanged.
      The action of AT-I was blocked by an AT1 receptor antagonist, suggesting that it
      was mediated by AT-II. Similarly, dexamethasone-induced ACE expression was
      present in human SMC, and calcium signaling was mobilized in response to AT-I in
      activated human cells. Experiments performed with cocultures of endothelial cells
      and SMC in a Transwell system showed that the response to AT-I was limited to the
      compartment where AT-I was localized, suggesting that AT-I does not pass through
      the endothelial cell barrier to interact with underlying SMC. Our data suggest
      that in rat, as in human SMC, the conversion of AT-I into AT-II and the signal
      transduction in response to AT-I are ACE expression-dependent. In addition, the
      present findings show that this SMC response to AT-I is endothelium-independent,
      supporting the idea of a local generation of AT-II in the vascular wall.

PMID- 11291770
TI  - Cyclooxygenase-1 and cyclooxygenase-2 expression in rat kidney and adrenal gland
      after stimulation with systemic lipopolysaccharide: in situ hybridization and
      immunocytochemical studies.
AB  - Cyclooxygenase-2 (COX-2) is a recently discovered isoform of cyclooxygenase that
      is inducible by various types of inflammatory stimuli. Although this enzyme is
      considered to play a major role in inflammation processes by catalyzing the
      production of prostaglandins, the precise location, distribution, and regulation
      of prostaglandin synthesis remains unclear in several tissues. Using in situ
      hybridization histochemistry, we investigated the induction of COX-1 and COX-2
      mRNA expression after systemic administration of a pyrogen, lipopolysaccharide
      (LPS), in kidney and adrenal gland in the rat. The COX-2 mRNA signals
      dramatically increased 1 h after LPS treatment in the kidney outer medulla and
      adrenal cortex, where almost no or little expression was observed in nontreated
      animals, and returned to control levels within 24 h. COX-2 mRNA levels increased
      in the kidney inner medulla 6 h after treatment. There was also a significant
      increase in mRNA levels in the kidney cortex and adrenal medulla. On the other
      hand, COX-1 mRNA levels did not show any detectable changes except in the kidney
      inner medulla, where a significant downregulation of mRNA expression was observed
      after LPS treatment. Light and electron immunocytochemistry using COX-2
      antibodies showed that strong COX-2 immunoreactivity was localized to certain
      cortical cells of the thick ascending limb of Henle. In addition, based on double
      staining with antiserum to nitric oxide synthase (NOS) four further cell
      populations could be identified in kidney cortex, including weakly COX-2
      positive, NOS-positive macula densa cells. After LPS treatment, changes in COX-2
      immunoreactivity could be observed in interstitial cells in the kidney medulla
      and in inner cortical cells in the adrenal gland. These results show that COX-2
      is a highly induced enzyme that can be up-regulated in specific cell populations
      in kidney and adrenal gland in response to inflammation, leading to the elevated
      levels of prostaglandins seen during fever. In contrast COX-1 mRNA levels
      remained unchanged in this experimental situation, except for a decrease in
      kidney inner medulla.

PMID- 11291771
TI  - Changes in distribution and molecular weight of the acrosomal protein acrin2
      (MC41) during guinea pig spermiogenesis and epididymal maturation.
AB  - In this study, we examined the localization and characteristics of an intra
      acrosomal protein, acrin2 (MC41), during guinea pig spermiogenesis and post
      testicular sperm maturation in the epididymis, using the monoclonal antibody
      MC41. Immunoelectron microscopy demonstrated not only a specific domain
      localization of acrin2 in the apical segment of the guinea pig sperm acrosome,
      but also its dynamic behavior according to the spermatid differentiation and
      passage through the epididymis, as follows: acrin2 was exclusively localized in
      the membrane of the endoplasmic reticulum of early-stage spermatids but was not
      detectable in the developing acrosome until spermatids reached the maturation
      phase. In the final stage of spermiogenesis, acrin2 became localized in the outer
      acrosomal membrane (OAM)/matrix-associated materials both in the small region
      posterior to the dorsal matrix and along the ventral margin of the acrosomal
      apical segment. The acrosomal location of acrin2 in caput epididymidal sperm was
      almost identical to that observed in the final step spermatids, but during
      maturation it became progressively more restricted in area until on distal cauda
      epididymidal sperm it remained only in the dorsal region. In Western blot
      analysis, the MC41 antibody recognized a 165-kDa protein in the mature sperm
      extract. Furthermore, it was demonstrated that molecular weight reduction of the
      protein occurred during sperm passage through the epididymis. These findings
      indicate that acrin2 changes progressively in both distribution and size during
      development and maturation of the acrosome.

PMID- 11291772
TI  - Expression of placental lactogen and cytokeratin in bovine placental binucleate
      cells in culture.
AB  - Binucleate cells are present in ruminant placenta and play an endocrine role in
      the production of many hormones during pregnancy. We isolated and cultured
      binucleate cells from bovine placenta at middle to late gestation and
      characterized these cells using immunofluorescence techniques. Enriched
      preparations of binucleate cells were obtained using Percoll density gradient
      centrifugation following collagenase digestion. Binucleate cells in culture
      preferentially attached to collagen-coated dishes rather than to noncoated
      plastic dishes. The cells gradually extended their edges on collagen substrata,
      and finally assumed a flattened morphology. Antibodies to placental lactogen (PL)
      and pregnancy-associated glycoprotein-1 (PAG-1) specifically stained the majority
      of round binucleate cells, but not the flat cells. We found that PL-positive
      binucleate cells were consistently devoid of cytokeratin. In contrast,
      cytokeratin was expressed in PL-negative binucleate cells as well as mononuclear
      epithelial cells. Furthermore, the PL-negative flat binucleate cells also
      developed intense cytokeratin networks in the cytoplasm. These results indicate
      that cytokeratin expression is inversely proportionate to that of PL in cultured
      binucleate cells. We conclude that downregulation of cytokeratin in binucleate
      cells is a function of the state of cellular differentiation.

PMID- 11291773
TI  - Ultrastructural study of polyspermy during early embryo development in pigs,
      observed by scanning electron microscope and transmission electron microscope.
AB  - Polyspermy is generally considered a pathological phenomenon in mammals.
      Incidence of polyspermy in porcine eggs in vivo is extremely high (30-40%)
      compared with other species, and polyspermy rate in the in vitro fertilized eggs
      in pigs can reach 65%. It is still unknown whether polyspermy to a certain degree
      is a physiological condition in pigs, and whether porcine eggs have any
      capability with which to remove the accessory sperm in the cytoplasm. The
      objectives in the present study are to observe the ultrastructural changes of
      accessory sperm during early embryonic development in pigs. A total of 58 normal,
      early embryos at one-, two, three-, and four-cell and morular stages were
      collected from gilts and were studied by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). The surface ultrastructure showed that
      sperm fusion with the zona pellucida was a continuous process during one-, two-,
      three-, and four-cell and morular stages, as observed by the SEM. Accessory sperm
      were present in the cytoplasm of cleaved embryos. The sperm heads in the
      cytoplasm of cleaved embryos did not decondense. TEM revealed the presence of a
      condensed sperm head within a lysosome (or phagolysosome) in a three-cell embryo.
      These observations suggest that polyspermy may be a physiological condition in
      pigs and that early embryos may develop to term if accessory sperm do not
      interrupt the embryo genome. Furthermore, lysosome activity could be another
      physiological mechanism for removing accessory sperm in the cytoplasm of
      fertilized eggs and cleaved embryos after fertilization in pigs.

PMID- 11291774
TI  - Immunohistochemical localization of zona pellucida proteins ZPA, ZPB and ZPC in
      human, cynomolgus monkey and mouse ovaries.
AB  - The zona pellucida of mammalian oocytes plays an important role in binding and
      activation of sperm cells during the molecular events leading to fertilization.
      The genes coding for the three zona pellucida glycoproteins ZPA, ZPB, and ZPC of
      various species including mouse, dog, and human have been cloned and sequenced by
      several groups. However, it has remained a matter of debate as to whether the
      oocytes alone or in conjunction with the surrounding granulosa cells express and
      deposit these proteins to form the zona pellucida matrix. Addressing this
      unresolved issue, we assessed the expression and localization of all three zona
      pellucida proteins in ovaries of human, cynomolgus monkey and mice using
      immunohistochemical methods. In addition, oocyte-specific expression of ZPC from
      the primordial stage onward was confirmed by in situ hybridization. In sections
      of human ovaries, ZPA, ZPB, and ZPC proteins were immunohistochemically detected
      in the cytoplasms of primordial oocytes and during later stages of
      folliculogenesis in the zona pellucida matrices of oocytes. In sections fixed
      with formalin, a clear homogeneous ring was visible around the oocyte and no
      staining of granulosa cells was observed. In contrast, staining of ZP proteins
      was also observed between granulosa cells when Bouin's reagent had been used for
      tissue fixation. Thus, the original zona pellucida architecture was better
      preserved by formalin fixation. We further demonstrated that dissolution of the
      zona pellucida of isolated bovine oocytes occurred after they were exposed to
      Bouin's reagent. In summary, these results demonstrate that in mice, monkeys and
      humans, zona proteins are expressed and assembled exclusively by the oocyte and
      not by the granulosa cells. Previously observed results of ZP expression by an
      involvement of granulosa cells might therefore be the result of an improper
      fixation of the tissues leading to the disruption of the zona pellucida.
      Additionally this study highlights the importance of choosing the correct
      fixative for immunohistochemistry, not only for the usual reason of retaining
      antigenicity, but rather to retain the entire architectural structure.

PMID- 11291775
TI  - NADPH-diaphorase histochemistry in the terminal abdominal ganglion of the
      crayfish.
AB  - Nitric oxide (NO) has an important modulatory role on the processing of sensory
      signals in vertebrates and invertebrates. In this investigation we studied the
      potential sources of NO in the terminal abdominal ganglion of the crayfish,
      Pacifastacus leniusculus, using NADPH-diaphorase (NADPHd) histochemistry, with
      NADPHd acting as a marker for NO synthase (NOS). In the terminal ganglion a mean
      of 27 strongly labelled NADPHd-positive cell bodies were found, and of these 80%
      [of stained cell bodies] [corrected] occurred in three regions located in antero
      lateral, central and posterior parts of the ganglion. Ventral and antero-ventral
      commissures as well as specific dorsal and ventral areas of the dendritic
      neuropil showed positive staining. Intense labelling was seen in the ventro
      medial tract, and in the connective between the terminal ganglion and the 5th
      abdominal ganglion. In addition, some motor neurones and neurones with branches
      in the sensory commissures were NADPHd positive. Our finding that NADPHd-positive
      cells occur in consistent patterns in the terminal abdominal ganglion implies
      that NO may have a role in mechanosensory processing in the crayfish.

PMID- 11291776
TI  - Development of the submucous plexus in the large intestine of the mouse.
AB  - In the small intestine of both embryonic birds and mammals, neuron precursors
      aggregrate first at the site of the myenteric plexus, and the submucous plexus
      develops later. However, in the large intestine of birds, the submucosal region
      is colonised by neural-crest-derived cells before the myenteric region (Burns and
      Le Douarin, Development 125:4335-4347, 1998). Using antisera that recognize
      undifferentiated neural-crest-derived cells (p75NTR) and differentiated neurons
      (PGP9.5), we examined the colonisation of the murine large intestine by neural
      crest-derived cells and the development of the myenteric and submucosal plexuses.
      At E12.5, when the neural crest cells were migrating through and colonising the
      hindgut, the hindgut mesenchyme was largely undifferentiated, and a circular
      muscle layer could not be discerned. Neural-crest-derived cells migrated through,
      and settled in, the outer half of the mesenchyme. By E14.5, neural-crest-derived
      cells had colonised the entire hindgut; at this stage the circular muscle layer
      had started to differentiate. From E14.5 to E16.5, p75NTR- and PGP9.5-positive
      cells were observed on the serosal side of the circular muscle, in the myenteric
      region, but not in the submucosal region. Scattered, single neurons were first
      observed in the submucosal region around E18.5, and groups of neurons forming
      ganglia were not observed until after birth. The development of the enteric
      plexuses in the murine large intestine therefore differs from that in the avian
      large intestine.

PMID- 11291777
TI  - Antiallergic effects of H1-receptor antagonists.
AB  - The primary mechanism of antihistamine action in the treatment of allergic
      diseases is believed to be competitive antagonism of histamine binding to
      cellular receptors (specifically, the H1-receptors), which are present on nerve
      endings, smooth muscles, and glandular cells. This notion is supported by the
      fact that structurally unrelated drugs antagonize the H1-receptor and provide
      clinical benefit. However, H1-receptor antagonism may not be their sole mechanism
      of action in treating allergic rhinitis. On the basis of in vitro and animal
      experiments, drugs classified as H1-receptor antagonists have long been
      recognized to have additional pharmacological properties. Most first-generation
      H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5
      HT effects, which might favourably affect the symptoms of the allergic response
      but also contribute to side-effects. These additional properties are not
      uniformly distributed among drugs classified as H1-receptor antagonists.
      Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene
      (LT) release from mast cells and basophils. In human challenge models,
      terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release.
      Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in
      the skin, but not the nose. In a nasal antigen challenge model, cetirizine
      pretreatment did not affect the levels of histamine and prostaglandin D2
      recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L
      arginine methyl ester (TAME) esterase activity, and LTs were reduced.
      Terfenadine, cetirizine, and loratadine blocked allergen-induced
      hyperresponsiveness to methacholine. In view of the complexity of the
      pathophysiology of allergy, a number of H1 antagonists with additional properties
      are currently under development for allergic diseases. Mizolastine, a new H1
      receptor antagonist, has been shown to have additional actions that should help
      reduce the allergic response. In animal models, mizolastine inhibits antigen
      induced eosinophil infiltration into mouse skin and into the nasal cavity of
      guinea-pigs. Mizolastine also significantly inhibits antigen-induced neutrophil
      infiltration into the bronchoalveolar lavage fluids of guinea-pigs. In addition,
      it inhibits arachidonic acid-induced paw oedema in rats without affecting
      carrageenin-induced rat paw oedema, suggesting an effect on LT generation. In
      man, mizolastine inhibits early and late antigen-induced soluble intercellular
      adhesion molecule 1 (ICAM-1) levels in skin blisters. It also inhibits
      anaphylactic release of histamine from rodent mast cells, LTC4 and LTB4 release
      from mouse bone-marrow-derived mast cells, LTC4 release from rat intestinal mast
      cells, and 5-lipoxygenase activity of polymorphonuclear neutrophils of guinea-pig
      intestines and rat basophilic leukaemia cells. It is clear that a number of H1
      antihistamines have multiple effects on the allergic inflammatory response. It is
      equally clear that these antiallergic effects are not uniformly shared among all
      drugs of this class. The assessment of the clinical significance of these results
      and research regarding the parts of the molecules responsible for these
      activities are underway.

PMID- 11291778
TI  - Clinical advantages of dual activity in urticaria.
AB  - Urticaria is a common disorder that adversely affects quality of life; work
      related and recreational activities are restricted, while rest, sleep, and
      emotions are seriously disturbed in a significant proportion of patients. The
      pathogenic mechanisms vary, but cutaneous mast-cell activation with release of
      histamine and other vasoactive or proinflammatory mediators is thought to be the
      final common pathway for lesion induction in most cases. A subsequent, but
      incompletely understood, late-phase allergic reaction seems to prolong the
      inflammatory process, particularly in certain chronic forms of the disorder.
      Although histamine is considered an important mediator of urticaria, additional
      substances, including the cysteinyl leukotrienes (LTs), are putative mediators of
      the immediate urticarial responses and the inflammatory events that follow in
      some types of urticaria. A second-generation antihistamine, mizolastine, which
      exhibits dual activity with selective H1-receptor antagonism and, as shown in
      animal studies, anti-5-lipoxygenase activity, represents an advance in the
      treatment of urticaria. It has rapid, potent and sustained action. At the
      recommended 10-mg dose, mizolastine suppresses the histamine-induced wheal
      reaction as early as 1 h after oral administration. Compared to placebo,
      mizolastine significantly reduces overall patient discomfort and pruritus in
      patients with chronic idiopathic urticaria. Double-blind, placebo-controlled
      studies have also shown mizolastine to be at least as effective as other second
      generation antihistamines. Furthermore, with long-term use of mizolastine over 1
      year, a reduction in pruritus and the number of urticarial episodes was
      maintained with no evidence of tachyphylaxis or tolerance. Mizolastine has also
      been shown to be an effective treatment for cold-induced urticaria, causing
      significant delay in the whealing response to the ice-cube test and also reducing
      the wheal diameter.

PMID- 11291779
TI  - Clinical advantages of dual activity in allergic rhinitis.
AB  - Symptoms of allergic rhinitis include sneezing; itching of the eyes, nose, and
      throat; nasal obstruction; and rhinorrhoea; they may be seasonal or perennial,
      depending on the causative allergen. The major symptom of perennial allergic
      rhinitis is nasal obstruction. Sneezing and rhinorrhoea are often present, but
      are less troublesome than in seasonal allergic rhinitis. Symptom relief is a
      priority in allergic rhinitis because patients have a severely impaired quality
      of life. The nasal vascular system is complex. Histamine acts on postcapillary
      venules during both the immediate and late phase of reactivity and causes plasma
      extravasation. Other inflammatory mediators can also induce this reaction. Thus,
      histamine antagonists that also have some additional antiallergic properties have
      advantages in the treatment of allergic rhinitis. Mizolastine is a second
      generation antihistamine that has been shown, in experimental studies, to possess
      5-lipoxygenase inhibitory properties in addition to its H1-receptor antagonistic
      activity. In the treatment of seasonal allergic rhinitis, mizolastine 10 mg/day
      has been shown to be effective in reducing nasal and ocular symptoms. It has been
      shown to be significantly more effective than placebo with a greater percentage
      of responders. Another study has shown that symptoms of seasonal allergic
      rhinitis in mizolastine-treated patients were reduced more significantly than in
      cetirizine-treated patients on the second and third days of treatment. In
      perennial allergic rhinitis, mizolastine significantly improved symptoms of nasal
      obstruction compared with placebo and also significantly reduced nasal membrane
      colour, nasal secretions, and mucosal swelling as shown by rhinoscopy. These
      effects were maintained over a 5-month treatment period. Mizolastine has also
      been shown to be at least as effective as loratadine, and in one trial even
      superior in the treatment of perennial allergic rhinitis.

PMID- 11291780
TI  - Allergic rhinitis: not purely a histamine-related disease.
AB  - Allergic rhinitis is an inflammatory disorder of the nasal mucosa typified by the
      symptoms of nasal itch, sneeze, anterior nasal secretions, and nasal blockage.
      These symptoms arise from the interaction between mediators and neural, vascular,
      and glandular structures within the nose. Nasal itch, sneezes, and rhinorrhoea
      are predominantly neural in origin, while nasal obstruction is predominantly
      vascular. Nasal biopsy studies show accumulation of eosinophils within the lamina
      propria and epithelium and an increase in tissue and cell surface basophils in
      both seasonal and perennial allergic rhinitis. These cells are in an activated
      state. Within the epithelium, increased numbers of mast cells, T cells and
      Langerhans' cells, which induce T-cell activation, are found. The accumulation of
      these cells can be linked to chemokine and cytokine generation by the epithelial
      cells themselves. Thus, the tissue cell recruitment is orchestrated by activated
      mast cells, T cells, and epithelial cells, with the recruited tissue eosinophils
      also contributing to their persistence at this site through autocrine mechanisms.
      Mast cells generate an array of mediators including histamine, tryptase,
      leukotrienes, and prostaglandins. Histamine is also generated by basophils.
      Eosinophils and basophils contribute to the leukotriene synthesis within the
      tissue. Histamine nasal insufflation induces nasal itch, sneeze, and rhinorrhoea
      as well as nasal blockage, thereby reproducing all the symptoms of allergic
      rhinitis. These effects are primarily mediated by H1-receptors, and H1-receptor
      antagonists are a prominent treatment. Antagonism of histamine at these receptors
      reduces symptoms by about 40-50%, with the greatest effect on the neurally
      mediated responses. Thus, histamine is a major mediator of allergic rhinitis, but
      not the sole contributor. Nasal insufflation with leukotrienes, prostaglandins,
      or kinins is associated with the development of nasal blockage. These mediators
      act primarily on the nasal vasculature and, in this respect, leukotrienes are
      potent mediators. Leukotrienes also induce plasma protein exudation, which
      contributes to the anterior nasal secretions. Studies with combination products
      have suggested that modifying the effects of both leukotrienes and histamine has
      complementary effects in relieving nasal symptoms, indicating that both these
      mediators are relevant to disease expression.

PMID- 11291781
TI  - Prevention of malnutrition.

PMID- 11291782
TI  - Malnutrition--importance of care.

PMID- 11291783
TI  - A study of dietary pattern, household food security and nutritional profile of
      under-five children of a community of West Bengal.
AB  - A cross-sectional study was carried out in a tribal community of West Bengal to
      study the dietary pattern, household food security, utilisation of services and
      nutrition profile of under-five children. It was observed that average calorie
      consumption was 2,236 with 48% food insecured families. Cereals, starchy food and
      green leafy vegetables consumption was higher than the recommended daily
      allowance while pulses (scarcely supplied in fair price shops), milk, oil and
      sugar were less than recommended daily allowance. Nearly 11% kcal were coming
      from alcohol consumption. Public distribution system should supply all essential
      items with an improved quality on a regular basis and supply during lean season
      should be ensured. Prevalence of malnutrition in the children under-five years of
      age was 80.90% and 9.26% were suffering from severe grades. More severely
      malnourished children were observed in the age group of 12-23 months, amongst
      female children, in the families where mothers were working and also in the
      families where numbers of sibling were 2 or more. Services available under
      Integrated Child Development Services Scheme were utilised by 47.3% children.

PMID- 11291784
TI  - Evaluation of vitamin A status during pregnancy.
AB  - Adequate maternal vitamin A nutrition is essential for successful pregnancy
      outcome and estimation of serum retinol among pregnant women enables a precise
      and objective assessment of vitamin A status, during pregnancy, even in
      subclinical state. In order to evaluate vitamin A status during pregnancy, and
      its relationship with personal and pregnancy related variables of the mother, 300
      antenatal clinic attenders were interviewed at RG Kar Medical College and
      Hospital, Calcutta and tested for serum retinol, using Carr-Price test. Serum
      retinol values less than 30 microg/dl and 20 microg/dl, in this study, were
      considered as poor and severe vitamin A deficiency respectively. According to
      this 14.7% and 4% pregnant women were found to be suffering from poor and severe
      vitamin A deficiency respectively. Clinical signs of vitamin A deficiency (eg,
      nightblindness) were reported only among 60% cases of the deficient population.
      The problems of vitamin A deficiency were associated with low literacy and poor
      nutritional status of the mother, advanced gestational age of current
      pregnancy,increased number of pregnancies, shorter interval between births and
      poor dietary intake of vitamin A rich foods during pregnancy. The study thus
      raises the question of supplementation of vitamin A, during pregnancy, in Indian
      context where habitual diets are either inadequate or deficient in vitamin A.

PMID- 11291785
TI  - Care for nutrition and development.
AB  - Optimal growth and development depend not only on food quality and availability,
      on access to health care services and a healthy environment but also on the care
      provided to the child especially during the first few years of life. Care refers
      to the actions and practices of caregivers on a day to day basis that translate
      food, heakh care, and water and sanitation supplies into good growth and
      development of children. It includes behaviours such as feeding, sanitation and
      hygiene, home health practices, preparing food for children, and providing
      psychosocial support for development. Families also are responsible for providing
      care for girls in the family and women. Care requires resources--both skills and
      capabilities, as well as economic resources. Some resources are easily
      recognised, such as education of the caregiver, but others are less often seen,
      including time of the caregiver, motivation of caregiver and male family members,
      organisational resources such as child care centres, and the caregiver's ability
      to influence decisions about child care. It must be noted that the poorer the
      family, the more risks for children in the environment. Therefore, the poorer the
      environment, the more important a role care has in children's survival, growth
      and development. Implications for health care providers include assessing the
      care practices in the home, and resources for care when making recommendations;
      supporting positive practices already being performed in order to empower the
      caregiver; checking the understanding and recall of the caregiver; and finally,
      recognising that all children, regardless of gender, ethnicity, case, economic
      level, etc, have a right to good nutrition and health care in order to develop to
      their fullest potential under the Convention for the Rights of the Child, acceded
      to by India in 1992.

PMID- 11291786
TI  - Nutrition scenario in India--implications for clinical practice.
AB  - India has the highest prevalence (and largest share) of malnourished children,
      low birth weight babies and anaemia levels amongst children and women in the
      world. Other micronutrient deficiencies (vitamin A and iodine) also constitute
      serious public health problems. Various government schemes set up to combat these
      problems have not had the expected impact in reducing malnutrtion or
      micronutrient deficiencies. This is not only due to low utilisation or inadequacy
      of the schemes but also due to the population not adopting appropriate behaviours
      to improve their health and nutrition. Providing correct and timely technical
      advice on nutrition to their patients and their families is often given
      inadequate emphasis by medical practitioners. But when we know that malnutrition
      contributes to 55% of child mortality which has been stagnating in most states,
      medical practitioners, whose advice on health matters is very much heeded by the
      population, can play an important role in reversing this trend.

PMID- 11291787
TI  - Micronutrient malnutrition--present status and future remedies.
AB  - Micronutrient deficiency is a serious public health concern in most of the
      developing countries which leads to malnutrition syndromes. The micronutient
      deficiencies which are of greatest public health significance include iron
      deficiency, vitamin A deficiency and iodine deficiency disorder. National Pilot
      Programme on Control of Micronutrient Malnutrition was launched in 1995 and the
      department of biochemistry and nutrition of the All India Institute of Hygiene
      and Public Health, Calcutta was entrusted to co-ordinate the activities. It
      presently covers five eastern and north-eastern states. Baseline situation
      analysis was conducted mainly on iron deficiency anaemia, iodine deficiency
      disorder and vitamin A deficiency. Comparing with WHO cut off figures, point
      prevalence of anaemia in various age groups was found to be high. Bitot's spot
      was mainly noted in the age group of 6-71 months. Nightblindness was found in the
      children of the age group of 24-71 months. High prevalence of nightblindness in
      pregnant women is a point of concern. Action needed to control micronutrient
      deficiency includes: Intervention strategies, extensive nutrition and health
      education, to support the problem specific programmes, to stregthen various state
      government programmes and strengthen role of NGOs.

PMID- 11291788
TI  - Promoting and supporting breastfeeding for optimal nutrition during infancy.
AB  - As general physician one can significantly influence a mother's or family's
      decision to optimally feed their baby and good feeding practices during first
      year greatly reduce the risk of a child being sick and being malnourished. It is
      recommended that health personnel should focus on exclusive breastfeeding for
      first six months and continued breastfeeding for up to two years along with
      appropriate and timely complementary foods that are started at the age of six
      months. Mothers need breastfeeding information and support during antenatal time;
      during hospital stay or at health care facility, and during postpartum visits.
      Encouragement especially during antenatal period increases breastfeeding rates.
      Subsequent paediatric and matemal visits are also important for promotion of
      breastfeeding. In this paper we would provide you new and updated information on
      recommended feeding practices, how you can support and help mothers, and what
      kind of skilled help is needed to initiate breastfeeding early, maintain
      exclusive breastfeeding and avoid artificial feeding. We will also discuss some
      strategies to support mothers.

PMID- 11291789
TI  - Nutrition in pregnancy and lactation.
AB  - Nutrition at optimal levels is fundamental in the maintenance of positive health.
      Matemal nutrition is very important for the course and outcome of pregnancy.
      Lactation represents a stage wherein health and nutritional status of the infant
      are dependent on the mother. Successful pregnancy and lactation require
      adjustments in maternal body composition, metabolism and function of various
      physioogical systems. A diet that meets matemal nutritional needs is required for
      these adjustments, so that maternal well-being is safeguarded with birth of an
      healthy infant. Adequate nutrition supports the growth of both matemal and foetal
      tissues. Chronic undernutrition throughout pregnancy affects birth weights of
      newborns. Poor nutrition causes intra-uterine growth retardation. Specific
      nutrients like zinc, iodine and folate are also required for development of the
      foetus. Foetal iron deficiency exists in maternal iron deficiency anaemia.
      Maternal nutritional status, breast milk composition and volume are elaborated in
      the article. Proteins, fats, minerals and vitamins and their requirements are
      narrated in detail. Additional nutritional requirements during lactation have
      been tabulated in this article. Thus improving the nutrition and health of girls
      and younger women and of mothers during pregnancy and lactation will derive
      benefits in terms of improved health of their children throughout their lives.

PMID- 11291790
TI  - Integrated child development services scheme (ICDS) in India: its activities,
      present status and future strategy to reduce malnutrition.
AB  - Integrated Child Development Services Scheme (ICDS) provides an integrated
      approach for converging all the basic services for improved child care, early
      stimulation and learning, health and nutrition, water and environmental
      sanitation aimed at the young children, expectant and lactating mothers, other
      women and adolescent girls in a community. Its objectives are: To improve
      nutritional and health status of children of 0-6 years; to reduce the incidence
      of mortality, morbidity, malnutrition and school dropout; to achieve effective co
      ordination amongst various departments to promote child development; to lay
      foundation of proper psychological,physical and social development of the child;
      to enahance mother's capability to look after normal health and nutritional needs
      of the child. ICDS services are provided through a village based centre ie, the
      Anganwadicentre for the services of: Supplementary nutrition, immunisation,
      health check-up, referral services, treatment of minor illnesses, nutrition and
      health education to women, preschool education to children and supports for water
      supply, sanitation, etc. Several government departments and their services are co
      ordinated at village, block, district, state and central levels. The
      Anganwadiworker is the most peripheral functionary which implements the programme
      services at the village/community level. In projects where able leadership has
      been provided, ICDS has been reported to be better. Though there are some
      shortcomings in ICDS, till future thrust of the programme is necessary for aiming
      of the upliftment of underprivileged section of the population. Operative
      research in various areas is suggested which can help in improving the efficiency
      of ICDS.

PMID- 11291791
TI  - Prevalence of anaemia and worm infestation in tribal areas of Madhya Pradesh.
AB  - The study was conducted among school going children (6-14 years) of Baiga,
      Abuihmadia and Bharia tribes of Madhya Pradesh to assess the prevalence of
      anaemia and intestinal parasitic infestation among themselves. A total of 776
      school going children were included in the study of whom blood samples of all and
      stool samples of 409 were collected. Their haemoglobin was measured and stool
      samples were examined under microscope for ova and cysts. The results revealed
      that 30.3% of the children had severe anaemia (Hb < 7g/dl) and 50% children had
      intestinal parasites. The most common parasites were hookworn (16.3%) and A
      lumbricoides (18.5%). Though hookworm ova loads indicated mild to moderate
      infestation in most of the children, the continued presence of worms in
      marginally nourished children could contribute significantly to blood loss in the
      intestine with resultant anaemia.

PMID- 11291792
TI  - Environmental management in Unilever.

PMID- 11291793
TI  - Interview with Anthony Burgmans, co-chairman of Unilever, on its environmental
      strategy.

PMID- 11291794
TI  - Service doctors and strikes: why.

PMID- 11291795
TI  - Media and medical profession.

PMID- 11291798
TI  - JIMA special issue on polio.

PMID- 11291796
TI  - Special issue on tuberculosis.

PMID- 11291799
TI  - Candid-B cream in the treatment of candidiasis with inflammatory dermatoses-
      National Study Group.
AB  - Physicians (n = 84) across the country prescribed candid-B cream (clotrimazole 1%
      + beclomethasone dipropionate 0.025%) on 822 patients suffering from candidiasis
      with inflammatory diseases to evaluate the efficacy and safety of the
      combination. The results showed reduction in severity was more than 80% for all
      symptoms/signs except scaling and lichenification where the reduction was 76.05%
      and 66.03% respectively. Only one patient complained of adverse reaction. So in
      the treatment of coexisting candidiasis and inflammatory dermatoses the
      combination of clotrimazole 1% + beclomethasone 0.025% (candid-B cream) was found
      to be highly effective.

PMID- 11291800
TI  - Role of autonomic influences in the initiation and perpetuation of focal atrial
      fibrillation.

PMID- 11291801
TI  - Interleukin-6 levels are inversely correlated with heart rate variability in
      patients with decompensated heart failure.
AB  - INTRODUCTION: Increased local and systemic elaboration of cytokines have an
      important role in the pathogenesis of congestive heart failure (CHF) through
      diverse mechanisms. Because cytokines are known to act at the neuronal level in
      both the peripheral and central nervous system, we sought to determine whether
      increased cytokine levels are associated with the autonomic dysfunction that
      characterizes CHF. METHODS AND RESULTS: We studied 64 patients admitted for
      decompensated CHF (mean age 59+/-12 years). Autonomic function was assessed using
      time- and frequency-domain heart rate variability (HRV) measures, obtained from
      24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor
      alpha (TNF-alpha), and interleukin-6 (IL-6) were measured in all patients. TNF
      alpha levels did not correlate with any of the HRV measures. IL-6 inversely
      correlated with the time-domain parameters of standard deviation of RR intervals
      (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR
      intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain
      parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency
      (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and
      indices of parasympathetic modulation. Using multiple linear regression models,
      adjusting for clinical variables and drug therapies, the strong inverse
      relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04),
      and ULF power (P = 0.0007) persisted. CONCLUSION: Reduction of long-term HRV
      indices is associated with increased levels of IL-6 in patients with
      decompensated heart failure. The ability of long-term HRV parameters to better
      reflect activation of diverse hormonal systems may explain their greater
      prognostic power for risk stratification in patients with CHF.

PMID- 11291802
TI  - The tangled web of heart failure: a complex network of surrogates and correlates.

PMID- 11291803
TI  - Acute and long-term effects of atrioventricular junction ablation and VVIR
      pacemaker in symptomatic patients with chronic lone atrial fibrillation and
      normal ventricular response.
AB  - INTRODUCTION: The precise role of irregular ventricular response in atrial
      fibrillation (AF) has not been fully elucidated. This study examined the
      independent effects of rhythm regularity in patients with chronic AF. METHODS AND
      RESULTS: This study included 50 patients who had chronic lone AF and a normal
      ventricular rate. Among these patients, 21 who underwent AV junction ablation and
      implantation of a VVIR pacemaker constituted the ablation group; the other 29
      patients were the medical group. Acute hemodynamic findings were measured in 21
      ablation patients before ablation (during AF, baseline) and 15 minutes after
      ablation (during right ventricular pacing). Compared with baseline data, ablation
      and pacing therapy increased cardiac output (4.7 +/- 0.8 vs 5.2 +/- 0.9 L/min; P
      = 0.05), decreased pulmonary capillary wedge pressure (16 +/- 5 vs 13 +/- 4 mmHg;
      P = 0.001), and decreased left ventricular end-diastolic pressure (14 +/- 4 vs 11
      +/- 3 mmHg; P < 0.05). After 12 months, the ablation group patients showed lower
      scores in general quality of life (-20%; P < 0.001), overall symptoms (-24%; P <
      0.001), overall activity scale (-23%; P = 0.004), and significant increase of
      left ventricular ejection fraction (44% +/- 6% vs 49% +/- 5%; P = 0.02) by
      echocardiographic examination. CONCLUSION: AV junction ablation and pacing in
      patients with chronic AF and normal ventricular response may confer acute and
      long-term benefits beyond rate control by eliminating rhythm irregularity.

PMID- 11291804
TI  - Everything old is new again.

PMID- 11291805
TI  - Breakthrough waves during ventricular fibrillation depend on the degree of
      rotational anisotropy and the boundary conditions: a simulation study.
AB  - INTRODUCTION: The left ventricle (LV) and right ventricle (RV) are characterized
      by specific fiber orientation known as "rotational anisotropy." However, it
      remains unclear whether the LV and RV are different with regard to the effect of
      rotational anisotropy on the dynamics of scroll waves during ventricular
      fibrillation (VF). To resolve this issue, we used a computation-based model to
      study scroll wave behavior. METHODS AND RESULTS: We composed an environment of
      simulated three-dimensional ventricular wall slabs, with optional ratios of fiber
      rotation to wall thickness (0 degrees, 6 degrees, and 12 degrees/mm thickness; LV
      10 mm, RV 5 mm), using Luo-Rudy phase I equations. When rotational anisotropy was
      not incorporated into the LV wall slab (theta endo to approximately theta epi = 0
      degrees), most scroll waves rotated around the filaments perpendicular to the
      tissue surface, with only a few accompanying breakthrough waves. In a twisted LV
      model (theta endo to approximately theta epi = 60 degrees and 120 degrees), the
      scroll waves were demonstrated as multiple wavelets scattered spatiotemporally,
      frequently accompanied by breakthrough waves that were promoted by rotational
      anisotropy. In a twisted RV model (theta endo to approximately theta epi = 30
      degrees and 60 degrees), single scroll waves and/or figure-of-eight reentrant
      waves appeared, with comparatively few breakthrough waves, regardless of the
      degree of fiber twist. CONCLUSION: The proportion of electrical effects of
      rotational anisotropy and tissue boundaries plays an important role in the
      genesis of breakthrough waves during VF, and the difference in wave propagating
      patterns and frequency spectrum of the ventricles may arise, in part, from the
      number of breakthrough waves promoted by rotational anisotropy.

PMID- 11291806
TI  - Heterogeneous changes of monophasic action potential induced by sustained stretch
      in atrium.
AB  - INTRODUCTION: Chronic enlargement of atrium is common in atrial fibrillation, and
      the effects of stretch on atrial action potentials seem inconsistent. As atrial
      muscle is heterogeneous, we suggest that atrial stretch induces a variable
      electrophysiologic response and that the effects of stretch are only partially
      mediated by stretch-activated channels. METHODS AND RESULTS: Sixteen guinea pig
      hearts were perfused by the Langendorff method using Kreb's solution with and
      without 80 microM streptomycin, which is a stretch-activated channel blocker.
      Suction electrodes were used to record monophasic action potentials (MAPs) of the
      left atrium. Left auricular pressure was monitored by a balloon. We determined
      the MAP duration at 50% and 90% repolarization (MAPD50 and MAPD90) in basal
      conditions and after a slow onset but sustained stretch of the atrium in the
      absence and presence of streptomycin. Stretch induced no overall consistent or
      significant change in mean MAPD50 and MAPD90. The individual responses were
      markedly variable. The most frequent response (about 50%) was a decrease in
      MAPD50 and MAPD90. In 25% of cases, there was no change, and in 25% we observed
      increases in MAPD50 and MAPD90. Streptomycin did not affect MAPD50 and MAPD90,
      but it dramatically modified the distribution of MAPD changes induced by stretch.
      In particular, streptomycin removed stretch-induced shortening of MAPD50 and
      MAPD90, whereas it did not affect stretch-induced lengthening. CONCLUSION:
      Sustained stretch of atrium induces variable modifications of MAPD that are only
      partially inhibited by streptomycin. This suggests the participation of ionic
      channels other than specific stretch-activated channels in the response of atrial
      myocardium to sustained stretch.

PMID- 11291807
TI  - Comparison of the effects on drug concentrations, electrophysiologic parameters,
      and termination of atrial fibrillation in dogs when procainamide and ibutilide
      are delivered into the right atrium versus intravenously.
AB  - INTRODUCTION: We tested the hypothesis that right intra-atrial (i.a.)
      administration of antiarrhythmic drugs resulted in higher peak serum drug
      concentrations, greater electrophysiologic effects, and greater efficacy for
      termination of atrial fibrillation (AF) than intravenous (i.v.) drug delivery.
      METHODS AND RESULTS: Eight dogs were treated with 9.7 mg/kg procainamide infusion
      and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 minutes. Each
      dog had both an electrophysiologic (EP) and an AF termination study during i.a.
      and i.v. drug administration at > or = 2-day intervals (total four studies each).
      Right atrial pacing capture threshold, right atrial effective refractory period
      (ERP), right atrial and right ventricular monophasic action potential (MAP)
      durations at 70% and 90% of repolarization (MAPD70, MAPD90), AH, HV, and QT
      intervals, QRS width, intra-arterial systolic and diastolic blood pressures, and
      cardiac output were measured at different time-points. Blood samples were drawn
      from the coronary sinus and femoral vein for drug level determination. The right
      atrium was paced at 400-msec cycle length throughout the study. AF was induced by
      rapid right atrial pacing and maintained by methacholine infusion at 1.5 to 3
      microg/kg/min. The sustained AF was allowed to persist for 10 minutes before
      starting the antiarrhythmic drug infusion. We found no significant difference
      between the procainamide concentrations in the coronary sinus and femoral vein
      during i.a. and i.v. drug delivery. The time course and extent of increase in
      right atrial ERP, MAPD70, MAPD90, and all the other measured EP parameters did
      not differ between the two routes of drug administration. No significant
      difference was found in termination of AF between i.v. (5/7 procainamide; 4/8
      ibutilide) or i.a. (3/8 procainamide; 3/8 ibutilide) drug delivery or between
      drugs (8/15 procainamide; 7/16 ibutilide). CONCLUSION: Our data do not support
      any beneficial effect of i.a. versus i.v. procainamide or ibutilide delivery.

PMID- 11291808
TI  - Inverse relation between input resistance and threshold current in canine cardiac
      syncytium.
AB  - INTRODUCTION: The present study was designed to examine the extent to which
      differences in input resistance contribute to the heterogeneity of excitability
      in canine endocardium. METHODS AND RESULTS: The experiments were performed in
      isolated canine right anterior papillary muscles. The preparations were
      superfused with oxygenated Tyrode's solution at 36 degrees to 37 degrees C.
      Conventional methods were used for recording and stimulation. To obtain pertinent
      data, two microelectrodes were inserted into the same cell or into two contiguous
      cells. One microelectrode injected intracellular hyperpolarizing current to
      polarize the membrane; the second microelectrode recorded the changes in
      transmembrane potential. The two micreoelectrodes were separated by 8 to 10
      microm. The procedure used provided input resistance and threshold current values
      for the doubly impaled cell or the two contiguous cell units. The same procedure
      was repeated at different sites of the preparation. The plot of input resistance
      versus threshold current showed a good fit (R2 = 0.97) between the experimental
      data and the curve for the rectangular hyperbola XY = 30 mV; therefore, the input
      resistance and the threshold current are inversely related. CONCLUSION: The
      results indicate that the canine cardiac syncytium is nonhomogeneous with respect
      to input resistance and that input resistance is inversely related to the minimal
      current needed to reach threshold. Accordingly, the electrical excitability of
      the cells studied also is inhomogeneous.

PMID- 11291809
TI  - Phased-Array intracardiac echocardiography to guide radiofrequency ablation in
      the left atrium and at the pulmonary vein ostium.
AB  - INTRODUCTION: We sought to evaluate the utility of a phased-array intracardiac
      echocardiography (ICE) device to identify left atrial (LA) and pulmonary vein
      (PV) anatomy; accurately guide radiofrequency ablation (RFA) to the right or left
      PV ostium and LA appendage (LAA); and evaluate PV blood flow before and after RFA
      using Doppler parameters. METHODS AND RESULTS: Twelve adult sheep were
      anesthetized and an Acuson 10-French, 7-MHz ICE transducer introduced via the
      internal jugular vein into the right atrium. The LA was imaged and PV anatomy and
      blood flow documented using two-dimensional and pulsed-wave Doppler. Mean LA
      dimensions were 4.6 +/- 0.4 x 3.5 +/- 0.5 cm; mean single right and left main PV
      ostium diameters were 1.5 +/- 0.2 and 1.3 +/- 0.3 cm; and mean right and left PV
      first-order branch diameters were 0.8 +/-0.2 and 0.6 +/- 0.1 cm. Mean PV maximum
      inflow velocity for the right PV were 0.30 +/- 0.05 m/sec and for the left PV
      were 0.35 +/- 0.04 m/sec. The PV ostia and LAA could be targeted accurately for
      RFA using ICE guidance. At pathologic evaluation, the mean distance of the lesion
      center to the right or left PV-LA junction was 3.0 +/- 2.0 mm. The mean distance
      of the lesion center to the posterior margin of the LAA was <4 mm in all cases.
      There was no significant increase in PV maximum inflow velocity or decrease in PV
      diameter following RFA at the PV ostium. Absence of PV obstruction was confirmed
      at pathology. CONCLUSION: Phased-array ICE allows detailed assessment of LA and
      PV anatomy when imaged from the right atrium; accurate guidance of RFA to the PV
      ostium and LAA; and immediate evaluation of PV patency after RFA.

PMID- 11291810
TI  - Passive current redistribution in the heart.
AB  - INTRODUCTION: Electrical stimuli produce a spatial distribution of voltage across
      the heart. We hypothesized that the potential difference between tissue near a
      stimulating electrode and a remote site could cause sufficient current to flow
      through a highly conductive wire connecting the two sites to directly stimulate
      the remote tissue. METHODS AND RESULTS: In six open chest pigs, we inserted a
      catheter with right ventricular (RV) and superior vena cava (SVC) coil
      electrodes. A wire was placed with one end contacting the epicardium 10 +/- 2 mm
      away from the RV electrode and the other end on left ventricular (LV) epicardium
      56 +/-14 mm from the RV end of the wire. Stimuli of 10 to 100 V were delivered to
      the RV and SVC electrodes. Potentials were recorded from two 252-electrode arrays
      placed over the RV and LV ends of the passive wire. The current induced in the
      wire was measured. A minimum stimulus of 15 +/- 6 V was needed between RV --> SVC
      electrodes to not only pace the RV but also to pace the LV through the passive
      wire as detected by the electrode array recordings. Current in the wire varied
      linearly with RV-SVC stimulus strength. CONCLUSION: Coupling RV and LV epicardium
      with a passive wire while stimulating the RV endocardium induced sufficient
      current in the wire to synchronously pace the LV.

PMID- 11291811
TI  - Nonthoracotomy implantable cardioverter defibrillator placement in children: use
      of subcutaneous array leads and abdominally placed implantable cardioverter
      defibrillators in children.
AB  - INTRODUCTION: The need to access the right ventricle might preclude transvenous
      placement of a defibrillation lead at implantable cardioverter defibrillator
      (ICD) placement, especially in small children or children with complex congenital
      heart defects. We investigated a subcutaneous array lead in addition to an
      abdominally placed "active can" ICD device in two children to avoid a
      thoracotomy. METHODS AND RESULTS: The first child (age 12 years, 138 cm, 41 kg)
      had transposition of the great arteries with a subsequent surgical intra-atrial
      correction by the Mustard technique. The second child (age 14 years, 161 cm, 54
      kg) had a single atrium and a single ventricle, d-transposition of the aorta, and
      atresia of the main pulmonary artery with a surgical anastomosis between the
      aorta and the right pulmonary artery by the Cooley technique. The defibrillation
      threshold was 18 J and <20 J at initial implantation and at generator replacement
      in the first patient and 20 J in the second patient. During follow-up of 6 years
      and 1 month, respectively, no ICD-related complications occurred. CONCLUSION: In
      children in whom endocardial, right ventricular placement of a defibrillation
      lead is precluded, defibrillation is possible and safe between an abdominally
      placed "active can" ICD device and a subcutaneous array lead. This approach may
      avoid a thoracotomy in children with no possibility for transvenous ICD
      placement.

PMID- 11291812
TI  - Implantable defibrillators in children: from whence to shock.

PMID- 11291813
TI  - Radiofrequency catheter ablation of postinfarction ventricular tachycardia from
      the proximal coronary sinus.
AB  - Optimum strategy for radiofrequency (RF) catheter ablation of ventricular
      tachycardia (VT) after inferior wall myocardial infarction (MI) that originates
      from the posteroseptal process of the left ventricle is not known. We describe a
      case report of a 57-year-old man who developed recurrent post-MI VT with ECG
      morphology consistent with this type of VT (i.e., left bundle branch block
      pattern with predominant R waves from V2 to V6 and left-axis deviation).
      Endocardial mapping and entrainment during VT demonstrated a critical isthmus of
      the reentrant circuit in the proximal coronary sinus. RF application terminated
      VT and rendered it noninducible.

PMID- 11291814
TI  - Knowing where to look.

PMID- 11291815
TI  - Sudden cardiac death: exploring the limits of our knowledge.
AB  - Despite progress in epidemiology, clinical profiling, and interventions, sudden
      cardiac death remains a major clinical and public health problem. There remain
      important unresolved issues that are challenges for future progress. Among these
      are a better understanding of the magnitude of the problem and methods of
      profiling risk for individuals, the etiology and mechanisms of cardiac arrest in
      individuals with and without previously identified structural heart disease,
      clinical strategies for primary and secondary prevention of sudden cardiac death,
      and further development of community programs for improving cardiac arrest
      survival in the out-of-hospital environment. Each of these areas of endeavor and
      potential progress are reviewed and discussed.

PMID- 11291816
TI  - Reverse excitation-contraction coupling: Ca2+ ions as initiators of arrhythmias.

PMID- 11291817
TI  - Supraventricular tachycardia with 2:1 atrioventricular block: what is the
      mechanism?

PMID- 11291818
TI  - Termination of reentrant atrial tachycardia by a nonpropagated extrastimulus.

PMID- 11291819
TI  - What is cardiac memory?

PMID- 11291820
TI  - Shoulder and neck complaints in customer relations: individual risk factors and
      perceived exposures at work.
AB  - Perceived psychosocial and biomechanical exposures, individual factors and pain
      in the shoulder and neck were recorded in two groups of female service workers
      (healthcare and shopping centre workers). The jobs investigated were
      characterized by 'much' direct human relations, 'little' sitting and 'much'
      standing, and were light work by physiological or biomechanical criteria but
      potentially psychosocially demanding. A screening survey (n = 400 females) was
      the basis for the selected sample (n = 66 females), which was the object of the
      main investigation of this study. Reliability of the questionnaires was tested in
      a separate group of female healthcare workers (n = 29). Heart rate recordings
      through the work day estimated workload. There was a high prevalence of shoulder
      and neck pain (> 50%) for both work groups. In the two populations it proved
      difficult to explain shoulder and neck pain by reported physical and psychosocial
      exposures or individual factors, except by the variable 'perceived general
      tension', which clearly differentiated workers with and without pain. The
      findings in this study indicated, first, that perceived general tension might be
      an independent risk factor for muscle pain and, second, that this might be
      related to personality factors. However, this putative relationship must be
      verified in a longitudinal study. As no variable describing exposures in the
      working environment was associated with shoulder and neck pain, the question is
      posed whether such complaints can be considered work-related. Alternatively, the
      variables used to describe mechanical and psychosocial exposures in this study
      may have low specificity in characterizing work-related risk factors for service
      workers with customer relations.

PMID- 11291821
TI  - Spinal shrinkage during repetitive controlled torsional, flexion and lateral bend
      motion exertions.
AB  - This experiment analysed the spinal shrinkage due to repetitive exertions
      confined to each of three separate axes (twist, lateral bend, flexion). While the
      experiment was performed twice with small technique modifications in the twisting
      task (and thus two data collections were performed), the essential components
      were as follows. A total of 20 subjects were loaded with an equal moment of 20 Nm
      in each of the three axes, on 3 separate days (one axis per day). Subjects
      performed each task for 20 min at 10 repetitions min(-1), where stadiometer
      measurements of standing height were taken prior to and immediately following the
      20 min exertion. The twisting task demonstrated significant spinal shrinkage
      (1.81 and 3.2 mm in the two experiments) between the pre- and post-stature
      measurements while no clear effect emerged for the other two tasks. These data
      suggest that repetitive torsional motions impose a larger cumulative loading on
      the spine when compared with controlled lateral or flexion motion tasks of a
      similar moment.

PMID- 11291822
TI  - Ergonomics of electronic mail address systems: related literature review and
      survey of users.
AB  - The paper reviews the cognitive ergonomics literature related to electronic mail
      (e-mail) address design. Based on this information, a survey of 160 users of
      current e-mail address system was conducted. The aim was to obtain information on
      likes, dislikes and difficulties associated with e-mail address and to obtain
      users' suggestions and input for improving the current e-mail address system. The
      survey results indicated that users want an improved e-mail address system with
      regard to shorter length, useful information and appropriate presentation of
      information.

PMID- 11291823
TI  - Ergonomics guidelines for designing electronic mail addresses.
AB  - The aim was to design a human-centred electronic mail (e-mail) address system
      based on networking technology and cognitive ergonomics. Based on the background
      literature and the results of users' survey, a conceptual model is developed for
      designing e-mail addresses. This model consists of e-mail address components of
      formats, domain length, meaningfulness, orientation and information type
      pertaining to recall, information association and categorization. Five hypotheses
      were proposed to test the conceptual model, and four experiments were conducted
      with 85 participants to test the hypotheses. The dependent variables were
      performance time, error rate and degree of satisfaction, and the independent
      variables were components of the e-mail addresses. The main results indicate that
      for a recall task, significantly lower total performance time (26.2%) and error
      rate (75%) were found for the hybrid formats (digits and letters) than for the
      letter format, and up to four characters was the best single domain length. For
      an information association task, embedding both geographical and organizational
      information significantly decreased the response time (10.9%) in comparison with
      only embedding organizational information. For a categorization task, embedding
      both geographical information and organizational information significantly
      decreased response time (40.7%) in comparison with only embedding organizational
      information. This research demonstrates the importance of human-centred design
      and provides guidelines in effectively designing e-mail addresses.

PMID- 11291824
TI  - Comparative study of the effects of auditory, visual and multimodality displays
      on drivers' performance in advanced traveller information systems.
AB  - A simulator study was conducted to compare 16 younger (mean age 22 years) and 16
      older (mean age 68 years) drivers' ratings of workload (time, visual,
      psychological stress) and performance of navigation and button-pushing
      (identification of vehicle or road hazards) tasks under both high- and low-load
      driving conditions when simple or complex advanced traveller information (ATI)
      was presented visually only, aurally only or by multimodality (visual and
      auditory) display. For all participants, both the auditory and multimodality
      displays produced better performance in terms of response times, total number of
      correct turns and subjective workload ratings than those of using the visual-only
      display. Participants using the multimodality display also made the fewest errors
      related to push-button and navigation tasks, and controlled their vehicles
      properly. The visual display led to less safe driving, apparently because it
      imposed higher demands on the drivers' attention. An age effect was found in the
      present study, with younger drivers performing better and reporting less stress
      than older drivers. Notably, however, use of the multimodality display
      significantly improved the older drivers' performance in the button-pushing task.

PMID- 11291825
TI  - Tracking ability in subjects symptomatic of cumulative trauma disorder: does it
      relate to disability?
AB  - Symptoms of upper extremity cumulative trauma disorders (CTDs) often include
      weakness, discomfort, pain, numbness and stiffness, which are generally assessed
      clinically by using static tests or isolated movements. Little is known about the
      dynamic, functional ability of the upper extremity in CTD, yet, more than
      impairment, performance variables may relate to disability. The objectives of
      this study were to determine whether a manual tracking task was sensitive to the
      presence of symptoms associated with CTD and whether tracking performance related
      to disability. Forty-five volunteers who had frequently experienced one or more
      symptoms consistent with upper extremity CTD for at least 1 year and 22 control
      subjects performed the manual tracking task. Using a hand-held stylus over a
      digitizing tablet, subjects tracked a target that moved pseudo-randomly and was
      displayed on a computer screen. The root mean square error of the linear
      difference between target and stylus positions provided a measure of overall
      performance accuracy. Quadrant specific performance was also calculated to
      determine whether the location of the target (hence hand and wrist position)
      influenced performance. Additionally, the symptomatic group completed the
      Disability of the Arm, Shoulder and Hand (DASH) questionnaire reflecting physical
      disability level. Performance accuracy was poorer in symptomatic subjects than
      controls (p<0.001) and was influenced by target location (p<0.0001). The overall
      performance was associated with physical disability (r = 0.54). The findings
      suggest that tracking performance is sensitive to the presence of CTD symptoms
      and related to disability level. Further validation is required to determine
      whether the performance measure is sensitive to disease progression or
      intervention-induced changes.

PMID- 11291826
TI  - Motor preparation in postural control in seated spinal cord injured people.
AB  - Spinal cord injured (SCI) people try to compensate for the loss of postural
      muscle function by increased use of non-postural muscles. Such alternative muscle
      use, however, may necessitate important modifications in motor control. In this
      study motor programming processes were investigated in three groups, i.e. in high
      thoracic SCI, low thoracic SCI and non-SCI subjects. A bimanual forward-reaching
      task, in which graded sitting balance perturbation was systematically invoked,
      was presented to the subjects as a visual precue choice reaction time (RT) task.
      Effects of movement preparation were examined by precuing reaching distance
      information. RT and movement times were recorded. Centre of pressure (CP)
      displacement was used as an indicator for sitting balance perturbation. Results
      indicated that high thoracic SCI subjects programmed balance-perturbing reaching
      movements as fast as did non-SCI subjects. Low thoracic SCI subjects, on the
      other hand, showed substantially longer programming times. This latter outcome is
      consistent with the hypothesis that the low thoracic SCI subjects adopted a more
      complex postural control strategy involving residual motor functions in an
      attempt to actively compensate for loss of postural muscle function. High
      thoracic SCI subjects, on the other hand, appeared to adopt a less complex and
      thus easier to programme postural control strategy.

PMID- 11291827
TI  - Chronic oral administration of CI-994: a phase 1 study.
AB  - OBJECTIVES: CI-994 (N-acetyl dinaline, PD 123654) is a novel oral agent active in
      a broad variety of murine and human tumor xenografts. While cytotoxic in the
      Brown Norway (BN) rat leukemia model, growth inhibition in other murine and human
      tumor xenografts is predominantly cytostatic. Its specific mechanism of action
      remains unknown. Following CI-994 administration, inhibition of both histone
      deacetylation and cellular proliferation at the G1 to S transition phase of the
      cell cycle are observed. This Phase 1 study in patients with solid tumors was
      carried out to determine a maximum tolerated daily oral dose (MTD) for CI-994
      administered on a chronic basis. METHODS: Fifty-three patients received CI-994
      daily for treatment durations ranging from 2 to 10 weeks. Dosage escalation
      proceeded in 2 phases; an Acute Dosing Phase (n = 11) to define the MTD for CI
      994 administered over 2 weeks and a Chronic Dosing Phase (n = 29) to define the
      MTD for daily administration for 8 weeks. Upon completion of the Chronic Dosing
      Phase, a third cohort of patients (n = 13) received CI-994 at the recommended
      Phase 2 dose and schedule with 2 additional single doses of drug administered
      separated by a 1-week washout to assess the effect of food on CI-994
      pharmacokinetics. RESULTS: Thrombocytopenia was dose limiting at the MTD of 8
      mg/m2/day for 8 weeks. Other toxicities included fatigue and gastrointestinal
      effects such as nausea, vomiting, diarrhea, constipation and mucositis.
      Pharmacokinetic studies revealed that peak plasma levels and AUC's generally
      increased with dose and that food intake did not affect the rate or extent of
      drug absorption. One patient with heavily pre-treated adenocarcinoma of the lung
      achieved a Partial Response (PR) lasting over 2 years and 3 additional patients
      achieved Stable Disease (SD), 1 each with non-small cell lung, colorectal, and
      renal cancer. CONCLUSIONS: The recommended Phase 2 starting dose is 8 mg/m2/day
      for 8 weeks repeated after a 2-week drug-free interval.

PMID- 11291828
TI  - Achievement of complete remission in refractory Hodgkin's disease with prolonged
      infusion of gemcitabine.
AB  - Although, in recent decades effective chemotherapy regimens have been developed
      for the treatment of Hodgkin's disease, the prognosis of patients who experience
      disease progression is still very poor. New treatment approaches are urgently
      required to salvage such patients. In a patient with Hodgkin's disease who failed
      to achieve complete remission with the escalated BEACOPP protocol, progression
      with bone marrow infiltration and B symptoms developed despite further treatment.
      Subsequently, gemcitabine was administered in a novel schedule as a four-hour
      infusion of 250 mg/m2 on days 1, 8, and 15, every four weeks. After the first
      cycle, the dose was reduced to 200 mg/m2 because of grade 3 neutropenia. The
      condition of the patient improved after the second cycle and no toxicity was
      observed during cycles 3-6. Complete remission was achieved. Two years after the
      end of gemcitabine therapy, the patient is in good clinical condition and in
      continuous complete remission without further treatment. This is the first report
      of the prolonged infusion of gemcitabine as a salvage therapy in Hodgkin's
      disease.

PMID- 11291829
TI  - Phase I study of irofulven (MGI 114), an acylfulvene illudin analog, in patients
      with acute leukemia.
AB  - Irofulven (MGI 114, 6-hydroxymethylacylfulvene, HMAF) is a semisynthetic illudin
      analog with broad in vitro anti-neoplastic activity. In this leukemia phase I
      study, we investigated the toxicity profile and activity of Irofulven in patients
      with primary refractory or relapsed acute myeloid leukemia (AML), acute
      lymphocytic leukemia (ALL), or myelodysplastic syndromes (MDS). Irofulven was
      given as an intravenous infusion over five minutes daily for five days. The
      starting dose was 10 mg/m2/day (50 mg/m2/course). Courses were scheduled to be
      given every 3-4 weeks according to toxicity and antileukemic efficacy. Twenty
      patients [AML: 17 patients; MDS: one patient; ALL: one patient; mixed lineage
      acute leukemia: one patient] were treated. Nausea, vomiting, hepatic dysfunction,
      weakness, renal dysfunction, and pulmonary edema were dose limiting toxicities,
      occurring in two of five patients treated at 20 mg/m2/day and two of three
      patients treated at 12.5 mg/m2/day. The MTD was defined as 10 mg/m2/day for five
      days. One patient with primary resistant AML achieved complete remission.
      Proposed phase II studies will further define the activity of Irofulven in
      patients with better prognosis AML and in other hematological malignancies, both
      as a single agent and in combination regimens, particularly with topoisomerase 1
      inhibitors.

PMID- 11291830
TI  - A phase I study of vitamin E, 5-fluorouracil and leucovorin for advanced
      malignancies.
AB  - Six patients with incurable malignancies were originally treated with vitamin E,
      3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus
      LCV (20 mg/m2 i.v. bolus daily x 5) with 5FU (425 mg/m2 i.v. bolus immediately
      following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, then
      every 5 weeks indefinitely. When 3 of the first 6 had grade 3/4 toxicity, six
      more patients were treated on the identical drugs and schedule. Seven of twelve
      total patients had one or more grade 3/4 toxicities. Neutropenia, abdominal pain,
      and diarrhea were most common. No patient had a documented response, though seven
      patients did have stable disease. Though the combination of vitamin E and
      chemotherapy was toxic, this trial demonstrated maximal therapeutic doses of
      vitamin E can be combined with standard 5FU and LCV, without significantly
      increasing the side effects of the chemotherapy itself.

PMID- 11291831
TI  - Phase 1 study of N1-N11-diethylnorspermine (DENSPM) administered TID for 6 days
      in patients with advanced malignancies.
AB  - This was a dose escalation Phase 1 trial designed to determine the maximum
      tolerated dose (MTD) and dose-limiting toxicities (DLT) of DENSPM. METHODS: Adult
      patients with refractory solid tumors were treated with DENSPM administered by
      intravenous infusion in 100 ml of normal saline over 30 minutes. The daily dose
      of DENSPM was divided into three equal doses administered approximately every
      eight hours for six days. Courses were repeated every 28 days. RESULTS: Twenty
      eight patients were enrolled in the study. Dose levels of DENSPM explored were 25
      mg/m2/day (3 patients), 50 mg/m2/day (9 patients), 60 mg/m2/day (5 patients), 75
      mg/m2/day (6 patients), 94 mg/m2/day (3 patients) and 118 mg/m2/day (2 patients).
      The DLT for DENSPM was central nervous system toxicity characterized by aphasia,
      ataxia, dizziness, vertigo and slurred speech occurring at dose levels > or = 94
      mg/m2/day, which was also the MTD. SAFETY: The most frequent drug-related adverse
      events were asthenia (9 patients), injection site reaction (6 patients) and
      anemia (6 patients). One patient was removed from the study due to CNS toxicity.
      There were no treatment-related deaths. No trends were observed regarding
      hematologic toxicities, biochemical changes or changes in vital signs. EFFICACY:
      Nineteen of the 28 patients enrolled in the study were assessed for response. No
      objective responses were observed. Five patients had stable disease as the best
      response to therapy. CONCLUSIONS: Because the DLT was CNS and because of the
      relatively low doses that could be safely administered on this schedule as
      compared with a once-a-day schedule, this regimen was not recommended for Phase
      2.

PMID- 11291832
TI  - The oral fluorinated pyrimidines.
AB  - The fluorinated pyrimidines have played a major role in the treatment of many
      common tumors since 5-fluorouracil (5FU) was first introduced. Studies of the
      cellular and clinical pharmacology of 5FU have led to an improved understanding
      of the mechanisms of action of this agent. This knowledge has allowed the optimal
      and rational development of fluoropyrimidine therapy, with significant
      therapeutic advances in recent years. Efforts to improve the therapeutic index of
      5FU have included alteration of schedule, and the addition of biochemical
      modulators such as folinic acid. Although protracted continuous infusion of 5FU
      has led to better response rates and decreased toxicity, the administration of
      5FU by protracted infusion is not only costly, but also inconvenient to the
      patient. Furthermore it is often associated with infectious and thrombotic
      complications related to the required indwelling intravenous catheter. Protracted
      oral administration is a rational route for administering 5FU, being preferred by
      the patient and the pharmaco-economist. The unpredictable and low oral
      bioavailability of 5FU initially discouraged this form of treatment. This problem
      has now been overcome by the new generation of oral fluoropyrimidines. Two main
      strategies have been pursued: 1) The administration of an inactive prodrug of
      5FU, which is absorbed intact, and subsequently converted to 5FU. Capecitabine is
      converted to 5FU by a 3 step enzymatic process. 2) The administration of 5FU with
      an inhibitor of dihydropyrimidine dehydrogenase (DPD) to minimise the erratic
      absorption and variable clearance of 5FU: the preparations UFT, S1, and
      ethinyluracil/5FU contain an oral fluoropyrimidine co-administered orally with
      inhibitors of this enzyme. The development and characteristics of these agents
      are discussed.

PMID- 11291833
TI  - Factors affecting the pharmacokinetics of CPT-11: the body mass index, age and
      sex are independent predictors of pharmacokinetic parameters of CPT-11.
AB  - This study was conducted to describe the relationship between pharmacokinetics of
      CPT-11 and its active metabolite SN-38, and clinical values with special emphasis
      on the influence of relative weight referring to the appropriateness of a
      conventional dose adjustment method by body surface area (BSA). Thirty-six
      patients received 100 mg/m2 of CPT-11 intravenously over 90 min. Body Mass Index
      (BMI) was used as a measure of relative weight which is calculated from the
      equation: BMI=weight(kg)/[height(m)]2. The area under the concentration-time
      curve (AUC) of CPT-11 was significantly correlated with sex, age, poorer
      creatinine clearance and indocyanine green retention test (ICG). The peak plasma
      concentration (Cmax) of CPT-11 was significantly correlated with sex a larger
      BMI, BSA and age. The AUC of SN-38 was significantly correlated with ICG. The
      volume of distribution at steady state of CPT-11 inversely correlated with BMI.
      Multiple regression analysis revealed that the best fitting model with
      significant independent predictors for AUC of CPT-11 included age and sex
      (F=6.93, R2=0.29). That of Cmax of CPT-11 included sex and BMI (F=8.96, R2=0.35).
      The only independent predictor of AUC of SN-38 was ICG (F=7.75, R2=0.19). These
      results indicated that several factors affect pharmacological behaviors of CPT-11
      even in patients with normal organ functions. The dose modification method based
      solely on BSA is not sufficient to reduce interpatient variability of cancer
      chemotherapy. The influence of relative weight, sex and age on
      pharmacokinetics/pharmacodynamics should be taken into consideration in every
      pharmacological approach to establish the ideal dose modification method.

PMID- 11291835
TI  - A phase II trial of pyrazoloacridine (PZA) in squamous carcinoma of the cervix--a
      Gynecologic Oncology Group Study.
AB  - PURPOSE: The Gynecologic Oncology Group performed a Phase II study to determine
      the response rate of Pyrazoloacridine (PZA) in patients with advanced, persistent
      or recurrent squamous carcinoma of the cervix. METHODS: PZA was administered at a
      dose of 750 mg/m2 intravenously over three hours every three weeks. RESULTS:
      Among 21 evaluable patients, there were no complete and one (4.2%) partial
      response. The major toxicities were hematologic. CONCLUSION: PZA at the dose and
      schedule employed has insignificant activity in this population.

PMID- 11291834
TI  - Phase II study of 4-ipomeanol, a naturally occurring alkylating furan, in
      patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND/PURPOSE: 4-Ipomeanol (IPO; NSC 394438), a naturally occurring furan
      isolated from common sweet potatoes (Ipomoea batatas) infected with the fungus
      Fusarium solani was the first agent to be developed by the National Cancer
      Institute based on a biochemical-biological rationale as an anticancer agent
      targeted specifically against lung cancer. Prior to clinical development, IPO was
      shown to induce pulmonary toxicity in the lungs of several mammalian species
      because the agent is metabolized to a highly reactive furan epoxide by specific
      cytochrome P450 monooxygenases found in pulmonary Clara cells and type II
      pneumocytes, which share biochemical features with bronchogenic carcinoma.
      However, instead of inducing the anticipated lung toxicity in patients with lung
      cancer in disease-directed phase I studies, hepatotoxicity was the principal
      toxic effect of IPO in humans. Based on the presumption that IPO may be
      preferentially activated by cytochrome P450 monooxygenases in liver cells and
      biochemically-related hepatic malignancies, a phase II study was conducted to
      determine the activity and evaluate the toxicity of IPO in patients with advanced
      hepatocellular carcinoma. PATIENTS AND METHODS: Nineteen patients with advanced
      measurable hepatocellular carcinoma were enrolled on the phase II trial. All
      patients had an Eastern Cooperative Oncology Group performance status of at least
      two, no evidence of pulmonary dysfunction, and had either no prior treatment or
      minimal prior therapy. Patients were treated with IPO at a dose of either 1032
      mg/m2, which was the maximum tolerated and recommended phase II dose previously
      derived for patients with normal hepatic function (15 patients) or 826 mg/m2 if
      they had serum bilirubin concentrations in the range of 2.0 to 3.0 mg/dL (four
      patients). Treatment was repeated every three weeks. Objective tumor response,
      the primary endpoint of the study, was assessed after every two courses of
      treatment, and both pulmonary function and lung density were rigorously monitored
      using successive pulmonary function testing and computerized tomography. RESULTS:
      All nineteen patients were evaluable for both response and toxicity. No major
      objective responses were observed. One patient had a minor, brief reduction in
      lung metastases. Although marker lesions and overall disease remained stable for
      at least 12 and 24 months in three and two patients, respectively, the median
      time to progression was three months and the median survival was five months for
      all patients. The principal toxicity was reversible elevations in hepatic
      transaminases, which occasionally resulted in dose reduction. No clinically
      significant pulmonary toxicity was noted. CONCLUSION: IPO at a dose of either 826
      or 1032 mg/m2 administered every three weeks did not demonstrate a relevant
      degree of clinical activity against advanced hepatocellular carcinoma. Further
      evaluations of TO is not recommended for this disease.

PMID- 11291836
TI  - Phase II study of high-dose lovastatin in patients with advanced gastric
      adenocarcinoma.
AB  - Lovastatin, an inhibitor of mevalonate synthesis, demonstrated in vitro antitumor
      activity against a variety of human cancer cells, especially in gastric
      adenocarcinoma cells at pharmacologically achievable concentrations. To determine
      the antitumor activity of this drug in advanced measurable gastric adenocarcinoma
      as well as to assess the toxicities and the pharmacokinetic features, we carried
      out a phase II study of high-dose lovastatin. Patients received lovastatin 35
      mg/kg/day for 7 consecutive days, with ubiquinone (60 mg qid p.o.) to prevent
      rhabdomyolysis. The treatment was repeated every 28 days. From March 1996 to
      January 1997, 16 patients (median age, 57 years; range, 34-68) were entered into
      the study, 14 of whom were evaluated for response and toxicity. No patient
      achieved a response. A total of 28 cycles were administered. The median number of
      cycles was 2 (range, 1 to 4). Anorexia was the most common toxicity (64%), but
      decreased oral intake was observed only in 3 cycles. Two patients developed
      myalgia with elevated muscle enzyme. When used in this dosage and schedule,
      lovastatin does not appear to be effective for patients with advanced gastric
      adenocarcinoma.

PMID- 11291837
TI  - A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients
      with advanced non-small cell cancer previously treated with chemotherapy.
AB  - PURPOSE: To test the efficacy and safety of the novel antitumor agent MGI-114
      (NSC 683863) in patients with advanced non-small cell lung cancer (NSCLC)
      previously treated with chemotherapy. METHODS: A two-stage accrual design was
      used to ensure detection of a true response rate of at least 20% with a type I
      error of .04. Eligible patients received 11 mg/m2 daily for five consecutive
      days. Cycles were repeated every 28 days. RESULTS: Fifteen patients received a
      total of 34 cycles of MGI-114. All patients had a performance status of 0 or 1.
      Eleven patients had previously received carboplatin and paclitaxel +/- radiation.
      Two patients had received cisplatin and CPT-11, one patient had received weekly
      paclitaxel, and one patient had received carboplatin and docetaxel. None of the
      first 15 patients enrolled experienced objective tumor response, and the study
      was closed. Forty percent of patients developed > or = grade 2 thrombocytopenia.
      Grade 3 nausea and > or = grade 2 vomiting were observed in 40% and 47% of
      patients respectively. Thirty-three percent of patients experienced > or = grade
      2 fatigue. CONCLUSIONS: MGI-114, at this dose and schedule, does not have
      significant activity as second line therapy for patients with advanced NSCLC.

PMID- 11291838
TI  - Toxicity and response evaluation of the interferon inducer poly ICLC administered
      at low dose in advanced renal carcinoma and relapsed or refractory lymphoma: a
      report of two clinical trials of the Eastern Cooperative Oncology Group.
AB  - PURPOSE: Phase II studies were conducted to evaluate the safety and efficacy of
      the interferon inducer Poly ICLC at low doses in advanced renal cancer and
      relapsed or refractory lymphoma. PATIENTS AND METHODS: Twenty-nine patients with
      advanced renal carcinoma and eleven patients with lymphoma were treated with poly
      ICLC. Patients received 0.25 mg/m2 of poly ICLC intravenously twice weekly three
      days apart until progression or unacceptable toxicity. RESULTS: There were no
      objective responses. Six patients with renal carcinoma had stable disease as best
      response with one patient receiving 62 weeks of therapy. Toxicity included grade
      3 anemia in 8 patients and grade 4 anemia in one patient. All patients were
      anemic prior to entry with a median grade 2 anemia at baseline. Grade 4
      neutropenia, thrombocytopenia and injection site pain occurred in one patient
      each. Grade 3 fever, chills or fatigue occurred in four, three, and three
      patients respectively. Any grade fever occurred in 10 patients (25.6%) and any
      grade chills occurred in 9 patients (23.1%). CONCLUSION: Poly ICLC at this dose
      and schedule is well tolerated in both patient populations and is inactive in
      renal carcinoma.

PMID- 11291839
TI  - Excellent response to gemcitabine in a massively pre-treated woman with extensive
      cutaneous involvement after recurrence of breast cancer.
AB  - A 50-year-old woman presented with local relapse of breast cancer 6 years after
      partial mastectomy. Relapse was accompanied by extended skin induration due to
      tumor cell embolization of dermal lymphatics. During the following years the
      patient was exposed to 11 different anti-tumor regimens including 13 cytotoxic
      drugs (including alkylating agents, antitumor antibiotics, vinca alcaloids,
      epipodophyllotoxins, and taxanes), 4 anti-hormonal, and 2 immunologic attempts.
      Paclitaxel achieved a prolonged local improvement for some 7 months, but further
      various treatments were ineffective. At that time gemcitabine therapy was
      initiated and tumor infiltration of the skin was visibly diminished only 2 weeks
      later. After that tumor regressed further for 5 months and remained stable with
      continued doses of gemcitabine during much of the woman's last year. The patient
      died of acute myeloid leukemia (AML) 4 years after the local recurrence of breast
      cancer. Since multiple treatments using a plethora of aggressive cytotoxic drugs
      may render several classes of chemotherapy agents ineffective due to cross
      resistance, it seems advisable to select mild agents that are not subject to
      multidrug resistance mechanisms and display a unique mode of action as
      demonstrated in this case by gemcitabine.

PMID- 11291840
TI  - Introducing the Spemann-Mangold organizer: experiments and insights that
      generated a key concept in developmental biology.
AB  - The "organizer paper", published by Hans Spemann and Hilde Mangold in 1924,
      initiated a new epoch in developmental biology. Also it marked the climax of
      Spemann's life-long research which began at the end of the nineteenth century.
      This introduction retraces some of the steps by which Spemann arrived at the
      organizer concept: The problem of amphibian lens induction including the so
      called lens controversy, the early constriction experiments creating double
      headed malformations, and the homeo- and heteroplastic transplantations during
      gastrula stages of the newt. Furthermore this paper will--based on historical
      documents--repudiate some objections raised to the contribution of Spemann and
      Hilde Mangold to the discovery and interpretation of the organizer effect.

PMID- 11291841
TI  - Induction of embryonic primordia by implantation of organizers from a different
      species. 1923.

PMID- 11291842
TI  - Evolution of the organizer and the chordate body plan.
AB  - The discovery of the organizer by Spemann and Mangold in 1924 raised two kinds of
      questions: those about the means of patterning the chordate body axis and those
      about the mechanisms of cell determination by induction. Some researchers,
      stressing the second, have suggested over the years that the organizer is poorly
      named and doesn't really organize because inducers act permissively, because they
      are not unique to the organizer, and because multipotent responsive cells develop
      complex local differentiations under artificial conditions. Furthermore, with the
      discovery of meso-endoderm induction in 1969, the possibility arose that this
      earlier induction generates as much organization as, or more than, does the
      organizer itself. Evidence is summarized in this article that the organizer does
      fulfill its title with regard to pattern formation: it adds greatly to embryonic
      organization by providing information about time, place, scale, and orientation
      for development by nearby members of the large multipotent competence groups
      surrounding the organizer. Embryos having smaller or larger organizers due to
      experimental intervention develop defective axial organization. Without an
      organizer the embryo develops no body axis and none of the four chordate
      characters: the notochord, gill slits, dorsal hollow nerve chord, and post-anal
      tail. For normal axis formation, the organizer's tripartite organization is
      needed. Each part differs in inducers, morphogenesis, and self-differentiation.
      The organizer is a trait of development of all members of the chordate phylum. In
      comparison to hemichordates, which constitute a phylum with some similarities to
      chordates, the chordamesoderm part is unique to the chordate organizer (the trunk
      tail organizer). Its convergent extension displaces the gastrula posterior pole
      from alignment with the animal-vegetal axis and generates a new anteroposterior
      axis orthogonal to this old one. Once it has extended to full length, its
      signaling modifies the dorsoventral dimension. This addition to the organizer is
      seen as a major event in chordate evolution, bringing body organization beyond
      that achieved by oocyte organization and meso-endoderm induction in other groups.

PMID- 11291843
TI  - Continuity and change: paradigm shifts in neural induction.
AB  - The problem of "primary embryonic induction" was one of the first areas of
      developmental biology to become "molecularized." What had been seen as an
      intractable series of problems became amenable to the techniques of Northern
      blotting, ectopic RNA insertion, and in situ hybridization. These molecular
      analyses showed that some of the fundamental concepts of primary embryonic
      induction concluded by experimental embryologists were false. First, primary
      embryonic induction was not primary. The organizer tissue, itself, was the
      product of a prior induction. Second, the neural fate of cells was not being
      induced. Rather, the epidermal fate was induced and the neural state was the
      default, uninduced, fate of ectodermal tissues. Third, primary embryonic
      induction was not something unique to vertebrates. Rather, the ventral neural
      cord of insects formed using the same mechanisms as the dorsal neural tube of
      vertebrates. Fourth, the brain formed in a matter distinctly different from that
      the spinal cord. Despite these differences, there has been a clear and strong
      continuity between the experimental embryological tradition and the molecular
      genetic tradition, and these new results are seen by many contemporary
      developmental geneticists as strengthening, rather than destroying, the older
      science.

PMID- 11291844
TI  - Formation and maintenance of the organizer among the vertebrates.
AB  - The organizer is established at the blastula stage of development, under the
      influence of a special region of cells known as the Nieuwkoop center in
      amphibians, where Vg1/activin-like signals overlap with activity of the Wnt
      pathway. Despite differences in their mode of early development, a similar region
      can be identified in other vertebrates. It has widely been assumed that once the
      organizer property is assigned to cells at this early stage, it is fixed so that
      by the gastrula stage, no new cells acquire organizer properties. However, when
      the organizer is ablated, it can regenerate for a limited period during
      gastrulation, a process regulated by both positive and negative signals emanating
      from various domains in the embryo. Here we compare the mechanisms that initially
      establish the organiser in the blastula with those that maintain it during
      gastrulation in different vertebrate classes, and argue that similar molecular
      mechanisms may be involved in the two processes. We also suggest that these
      mechanisms are required to ensure the appropriate location of the organizer
      property in the gastrula, where cells are continuously moving.

PMID- 11291845
TI  - Organizer and axes formation as a self-organizing process.
AB  - It is a widely held view that axis formation is based essentially on pre
      localized determinants. However, the robustness of early development, the pattern
      regulation observed after experimental interferences and the existence of systems
      that don't require maternal determinants suggest that self-regulating pattern
      forming systems are also involved. A model is proposed that allows axes formation
      by a chain of reactions based on local self-enhancement and long-range
      inhibition. Their appropriate linkage ensures that the intermediary patterns
      emerge in the correct sequence and have the correct spatial relation to each
      other. Specifically, the model comprises the following events: the generation of
      a pole by a pattern-forming process, the formation of a second organizer
      eccentric to the pole (e.g. the Nieuwkoop center), the ecto-meso-endo
      subdivision, the generation of the Spemann-Mangold organizer with its anterior
      posterior subdivision under the influence of the Nieuwkoop center, the conversion
      of the Spemann-Mangold organizer (a hot spot) into the notochord (a hot stripe),
      and the marking of the left side of the organism by a patterning reaction
      influenced by the midline. The pattern forming reactions do not depend on but can
      make use of maternally pre-localized determinants or asymmetries. Comparison with
      known genes and molecules reveals that many of the expected ingredients are
      present. Computer simulations show that the model accounts for many regulatory
      features reported in the literature. The computer simulations are available in an
      animated form at.

PMID- 11291847
TI  - Formation of a functional morphogen gradient by a passive process in tissue from
      the early Xenopus embryo.
AB  - In early development much of the cellular diversity and pattern formation of the
      embryo is believed to be set up by morphogens. However, for many morphogens,
      including members of the TGF-beta superfamily, the mechanism(s) by which they
      reach distant cells is unknown. We have used immunofluorescence to detect, at
      single cell resolution, a morphogen gradient formed across vertebrate tissue. The
      TGF-beta ligand is distributed in a gradient visible up to 7 cell diameters
      (about 150-200 microm) from its source, and is detectable only in the
      extracellular space. This morphogen gradient is functional, since we demonstrate
      activation of a high response gene (Xeomes) and a low-response gene (Xbra) at
      different distances from the TGF-beta source. Expression of the high affinity
      type II TGF-beta receptor is necessary for detection of the gradient, but the
      shape of the gradient formed only depends in part on the spatial variation in the
      amount of receptor. Finally, we demonstrate that the molecular processes that
      participate in forming this functional morphogen gradient are temperature
      independent, since the gradient forms to a similar extent whether the cells are
      maintained at 4 degrees C or 23 degrees C. In contrast, TGF-beta1 internalisation
      by cells of the Xenopus embryo is a temperature-dependent process. Our results
      thus suggest that neither vesicular transcytosis nor other active processes
      contribute to a significant extent to the formation of the morphogen gradient we
      observe. We conclude that, in the model system used here, a functional morphogen
      gradient can be formed within a few hours by a mechanism of passive diffusion.

PMID- 11291848
TI  - A study of Xlim1 function in the Spemann-Mangold organizer.
AB  - The Spemann-Mangold organizer is required in amphibian embryos to coordinate cell
      fate specification, differentiation of dorsal cell types and morphogenetic
      movements at early stages of development. A great number of genes are
      specifically expressed within the organizer, most of them encoding secreted
      proteins and transcription factors. The challenge is now to uncover genetic
      cascades and networks of interactions between these genes, in order to understand
      how the organizer functions. The task is immense and requires loss-of-function
      approaches to test the requirement for a given factor in a specific process. For
      transcription factors, it is possible to generate inhibitory molecules by fusing
      the DNA binding region to a repressor or activator domain, which should in
      principle antagonize the activity of the endogenous protein at the level of the
      DNA targets. We used this strategy to design activated and inhibitory forms of
      the LIM homeodomain transcription factor Lim1, which is encoded by an organizer
      gene involved in head development, as revealed by analyses of knockout mice. We
      found that Lim1 is a transcriptional activator, and can trigger dorso-anterior
      development upon ventral expression of hyperactive forms, in which Ldb1 is fused
      to Lim1. Using inhibitory Lim1 fusion proteins, we found that Lim1, or genes
      closely related to it, is required for head formation as well as for notochord
      development. Co-expression experiments revealed that Lim1 is required downstream
      of the early organizer factor Siamois, first, to establish the genetic program of
      the organizer and second, to mediate the action of organizer agents that are
      responsible for blocking ventralizing activities in the gastrula.

PMID- 11291846
TI  - Molecular mechanisms of cell-cell signaling by the Spemann-Mangold organizer.
AB  - We review how studies on the first Spemann-Mangold organizer marker, the homeobox
      gene goosecoid, led to the discovery of secreted factors that pattern the
      vertebrate embryo. Microinjection of goosecoid mRNA formed secondary axes and
      recruited neighboring cells. These non-cell autonomous effects are mediated in
      part by the expression of secreted factors such as chordin, cerberus and Frzb-1.
      Unexpectedly, many of the molecules secreted by the Spemann-Mangold organizer
      turned out to be antagonists that bind growth factors in the extracellular space
      and prevent them from binding to their receptors. The case of chordin is reviewed
      in detail, for this molecule has provided biochemical insights into how
      patterning by Spemann's organizer can be regulated by diffusion and proteolytic
      control. The study of the BMP-binding repeats of Chordin, which are present in
      many extracellular proteins, may provide a new paradigm for how cell-cell
      signaling is regulated in the extracellular space not only in embryos, but also
      in adult tissues.

PMID- 11291849
TI  - Making mesoderm--upstream and downstream of Xbra.
AB  - The mesoderm of the amphibian embryo is formed through an inductive interaction
      in which cells of the vegetal hemisphere of the embryo act on overlying
      equatorial cells. My laboratory is studying the Brachyury gene, which plays a key
      role in this interaction, being both necessary and sufficient for normal mesoderm
      formation. In this article I describe our attempts to understand how Xenopus
      Brachyury (Xbra) is activated in the right cells at the right time, and then to
      understand how Xbra exerts its effects.

PMID- 11291850
TI  - Regulation of convergent extension in Xenopus by Wnt5a and Frizzled-8 is
      independent of the canonical Wnt pathway.
AB  - The Wnt signaling pathway is increasingly recognized as a highly branched
      signaling network. Experimental uncoupling of the different branches of this
      pathway has proven difficult, as many single components are shared downstream by
      multiple, distinct pathways. In this report, we demonstrate that the upstream Wnt
      antagonists Xwnt5a and Nxfz-8, which inhibit normal morphogenetic movements
      during Xenopus gastrulation, act independently of the canonical Wnt signaling
      pathway. This finding is important, as it highlights the promiscuity of upstream
      Wnt signaling components and further establishes an important role for non
      canonical Wnt signaling in Xenopus morphogenesis.

PMID- 11291851
TI  - Generation of the germ layers along the animal-vegetal axis in Xenopus laevis.
AB  - After completion of gastrulation, typical vertebrate embryos consist of three
      cell sheets, called germ layers. The outer layer, the ectoderm, which produces
      the cells of the epidermis and the nervous system; the inner layer, the endoderm,
      producing the lining of the digestive tube and its associated organs (pancreas,
      liver, lungs etc.) and the middle layer, the mesoderm, which gives rise to
      several organs (heart, kidney, gonads), connective tissues (bone, muscles,
      tendons, blood vessels), and blood cells. The formation of the germ layers is one
      of the earliest embryonic events to subdivide multicellular embryos into a few
      compartments. In Xenopus laevis, the spatial domains of three germ layers are
      largely separated along the animal-vegetal axis even before gastrulation;
      ectoderm in the animal pole region; mesoderm in the equatorial region and
      endoderm in the vegetal pole region. In this review, we summarise the recent
      advances in our understanding of the formation of the germ layers in Xenopus
      laevis.

PMID- 11291852
TI  - Dickkopf1 and the Spemann-Mangold head organizer.
AB  - Work in amphibians indicates that inhibition of Wnt and BMP signals is essential
      for head development and that head induction by the Spemann-Mangold organizer may
      be mediated by secreted Wnt antagonists. Wnts are potent posteriorizing factors
      and antagonize the Spemann-Mangold organizer. Dickkopf1 (dkk1) encodes a secreted
      effector expressed in head organizing centers of Xenopus, mouse and zebrafish. It
      acts as a Wnt inhibitor and is able together with BMP inhibitors to induce the
      formation of ectopic embryonic heads in Xenopus. It anteriorizes both mesendoderm
      and neuroectoderm, promoting prechordal plate and forebrain fates. Injection of
      inhibitory antibodies leads to microcephaly and cyclopia. Dkk1 thus is an
      essential mediator of the vertebrate head organizer.

PMID- 11291853
TI  - Siamois cooperates with TGFbeta signals to induce the complete function of the
      Spemann-Mangold organizer.
AB  - In Xenopus, the Spemann-Mangold organizer induces and patterns the body axis.
      Siamois, a Wnt-responsive transcriptional activator, functions to establish and
      maintain the Spemann-Mangold organizer by regulating organizer gene
      transcription. While expression of Siamois in marginal blastomeres induces an
      axis consisting of both head and trunk structures, we show that expression of
      Siamois in animal blastomeres induces an axis that lacks head structures.
      Consistent with the absence of head organizer activity in Siamois-expressing
      animal pole tissue, Siamois did not induce animal expression of Cerberus, Frzb1
      and Xlim1, genes implicated in anterior development. A dominant negative form of
      Siamois inhibited endogenous expression of Cerberus, Frzb1 and Xlim1, indicating
      that Siamois is necessary for organizer-specific expression of these head
      organizer genes, but is not sufficient in animal tissue. Siamois induces
      Cerberus, Frzb1 and Xlim1 in vegetal blastomeres and vegetal induction by Siamois
      is dependent on endogenous TGFbeta signals. The results provide evidence that
      Siamois cooperates with TGFbeta signals to activate the expression of organizer
      genes and to generate an organizer with both head- and trunk-inducing activity.

PMID- 11291854
TI  - The Spemann-Mangold organizer: the control of fate specification and
      morphogenetic rearrangements during gastrulation in Xenopus.
AB  - Vertebrate embryonic development is controlled by sequentially operating
      signalling centres that organize spatial pattern by inductive interactions. The
      embryonic body plan is established during gastrulation through the action of the
      Spemann-Mangold or gastrula organizer, a signalling source discovered 75 years
      ago by Hans Spemann and Hilde Mangold. Transplantation of the organizer to a
      heterotopic location in a recipient embryo results in the formation of a
      secondary embryonic body axis, in which several tissue types, most notably
      somites and the neural tube, are derived from ventral host cells. Because of
      these non-cell autonomous recruiting or inducing activities the organizer has
      become a paradigm for studying intercellular communication in the vertebrate
      embryo. Here, I review some of the recent advances in understanding 1) the
      initiation of the Spemann-Mangold organizer, 2) its function in pattern formation
      along the dorsal-ventral and anterior-posterior axes and 3) the integration of
      cell fate specification events and downstream execution of morphogenetic
      movements during gastrulation in Xenopus laevis.

PMID- 11291855
TI  - Functional analysis of the Xenopus frizzled 7 protein domains using chimeric
      receptors.
AB  - Seven-transmembrane receptors of the frizzled family can interact with secreted
      Wnt ligands and transmit Wnt signals into the cell. Dependent on the ligand
      receptor combination, distinct Wnt pathways are activated. Xenopus frizzled 7
      (Xfz7) and Xwnt-8b as well as Human frizzled 5 (Hfz5) and Xwnt-5a can act
      synergistically in the activation of Wnt/beta-catenin target genes siamois (Xsia)
      and nodal related 3 (Xnr3) and in the induction of ectopic axes in Xenopus
      embryos. In order to characterize the role of different protein domains of Xfz7
      in Wnt/beta-catenin signaling, chimeric Xfz7/Hfz5 receptors were generated in
      which the extracellular (N5-TC7) or the intracellular domains (NT7-C5) between
      Xfz7 and Hfz5 were exchanged. We present evidence that the extracellular domain
      of Xfz7 can interact with Xwnt-5a and that the intracellular C-terminus can
      transmit a Wnt/beta-catenin signal. Despite these abilities, Xfz7 and Xwnt-5a do
      not act synergistically in the activation of Wnt/beta-catenin targets. This
      implies that the interaction of a frizzled receptor with different ligands can
      result in distinct cellular responses.

PMID- 11291856
TI  - Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus
      mesoderm.
AB  - Fox (forkhead/winged helix) genes encode a family of transcription factors that
      are involved in embryonic pattern formation, regulation of tissue specific gene
      expression and tumorigenesis. Several of them are transcribed during Xenopus
      embryogenesis and are important for the patterning of ectoderm, mesoderm and
      endoderm. We have isolated three forkhead genes that are activated during
      gastrulation and play an important role in the dorso-ventral patterning of the
      mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in
      embryonic pattern formation, is expressed in the Spemann-Mangold organizer region
      and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine
      Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or
      lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral
      plate mesoderm, but not in the notochord or presomitic mesoderm. Expression
      pattern and functional experiments indicate that these three forkhead genes are
      involved in the dorso-ventral patterning of the mesoderm.

PMID- 11291857
TI  - In vitro induction systems for analyses of amphibian organogenesis and body
      patterning.
AB  - The discovery that some well-known growth factors have inducing activity in
      embryogenesis has accelerated our understanding of embryonic induction. Relevant
      receptors, signal transduction pathways and patterns of gene expression have been
      characterized over the past decade. Amphibian embryos have provided an excellent
      model for analysis of embryonic induction because they are easily surgically
      manipulated and cultured in vitro, and with the addition of treatment with
      various inducing factors we have been able to control organogenesis and body
      patterning during early development in vitro. Activin A, a TGF-beta family
      protein, has a potent mesoderm-inducing activity on the isolated ectoderm called
      the animal cap. Activin induces animal caps to differentiate into various
      mesodermal and endodermal tissues, including beating hearts, in a dose-dependent
      fashion. Activin, in combination with retinoic acid, also induces the formation
      of the pronephros, a primitive embryonic kidney. The in vitro induced kidney was
      confirmed to function in vivo in a transplantation experiment. Furthermore, the
      activin-induced animal caps organize heads or trunk-and-tails in exactly the same
      manner as the organizer. The potential use of in vitro induction systems to
      further our understanding of vertebrate organogenesis and body patterning will be
      discussed.

PMID- 11291858
TI  - The avian organizer.
AB  - The development of avian embryos is characterized by the large amount of yolk
      present from the one-cell stage until late phases of organogenesis. In the chick,
      an axis of bilateral symmetry is established already before egg laying, when the
      egg rotates in the uterus. There is evidence for an active Wnt-catenin pathway in
      the vegetal cells in the periphery of the multi-cellular embryo. It overlaps with
      the posteriorly restricted expression of genes characterizing the vegetal
      hemisphere in amphibia. The zone of overlap bears several functional
      characteristics of a Nieuwkoop center, which is first apparent in the posterior
      marginal zone, but continues into the early primitive streak. Only the anterior
      part of the late streak is capable of direct neural induction, and only its tip,
      Hensen's node, can induce an anterior neural identity. This latter activity
      leaves the node together with the cells representing the anterior mesendoderm.
      Thus, although the constraints and dynamics of avian development make comparisons
      with the amphibian situation a complex undertaking, Hensen's node comes as close
      as possible to an organizer in Spemann and H. Mangold's definition.

PMID- 11291859
TI  - Nodal signaling and the zebrafish organizer.
AB  - Systematic genetic screens in zebrafish have led to the discovery of mutations
      that affect organizer function and development. The molecular isolation and
      phenotypic analysis of the affected genes have revealed that TGF-beta signals of
      the Nodal family play a key role in organizer formation. The activity of the
      Nodal signals Cyclops and Squint is regulated extracellularly by the EGF-CFC
      cofactor One-eyed Pinhead and by antagonists belonging to the Lefty family of TGF
      beta molecules. In the absence of Nodal signaling, the fate of cells in the
      organizer is transformed from dorsal mesoderm to neural ectoderm. Differential
      Nodal signaling also patterns the organizer along the anterior-posterior axis,
      with high levels required for anterior cell fates and lower levels for posterior
      fates. In addition, Nodal signaling cooperates with the homeodomain transcription
      factor Bozozok in organizer formation and neural patterning. The combination of
      genetic, molecular and embryological approaches in zebrafish has thus provided a
      framework to understand the mechanisms underlying organizer development.

PMID- 11291860
TI  - The role of the homeodomain protein Bozozok in zebrafish axis formation.
AB  - The zebrafish bozozok (boz) gene encoding a homeodomain protein (also named
      Dharma/Nieuwkoid) is required during blastula stages for the formation of a
      complete Spemann-Mangold gastrula organizer and subsequent development of axial
      mesoderm and anterior neural structures. Expression of bozin the dorsal yolk
      syncytial layer (YSL) and overlying marginal blastomeres is activated by beta
      catenin. Bozozok itself acts as a transcriptional repressor, and promotes
      organizer formation by directly inhibiting expression of the bmp2b (swirl) gene
      and by negatively regulating Wnt signaling by an unknown mechanism. boz
      cooperates with the Nodal-related secreted factors, Cyclops and Squint, in
      organizer formation. The incomplete organizer in boz mutants is deficient in
      expression of a number of factors such as Chordin that antagonize Bone
      morphogenetic proteins (Bmps), and Dickkopf 1, a Wnt antagonist. Conversely, the
      dorsal blastoderm of boz mutants exhibits ectopic expression of genes normally
      excluded from the dorsal midline such as wnt8 or tbx6. boz specifies the
      formation of anterior neuroectoderm by regulating Bmp and Wnt pathways in a
      fashion consistent with Nieuwkoop's two-step neural patterning model. boz
      promotes neural induction by limiting the anti-neuralizing activity of Bmp
      morphogens. In addition, by negative regulation of Wnt signaling, boz limits
      posteriorization of neuroectoderm. bozozok chordino double mutants exhibit a
      synergistic loss of head and trunk. This synthetic phenotype is due to
      dramatically increased Bmp signaling and consequent massive accumulation of cells
      in the tailbud at the expense of dorso-anterior structures. Therefore, boz and
      din act in overlapping pathways that provide the main mechanism to limit Bmp
      signaling in the zebrafish gastrula and allow for head and trunk development.
      Notably, Bozozok appears to function by repressing transcription of target genes
      such as swr (bmp2b) gene, and as such is the earliest acting repressor that the
      nascent dorsal axis is using to antagonize ventral influences.

PMID- 11291861
TI  - Role of the anterior visceral endoderm in restricting posterior signals in the
      mouse embryo.
AB  - Recent genetic and embryological experiments have demonstrated that head
      formation in the mouse embryo is dependent on signals provided by two organising
      centers during gastrulation, the anterior visceral endoderm (AVE) and the
      anterior primitive streak (also called the Early Gastrula Organiser, EGO).
      However the molecular nature of the signals triggering anterior neural formation
      from the epiblast is not clearly understood. The analysis of mouse mutants has
      allowed the identification of some of the molecular players involved in the
      process of head formation. In this review, we describe different mutant embryos
      in which impairment of visceral endoderm function leads to similar defects in
      antero-posterior axis specification. These phenotypes are consistent with a role
      of the AVE in protecting anterior embryonic regions from signals that promote
      posterior development. We propose that a genetic cascade in the AVE, involving
      HNF3beta, Lim1, Otx2, Smad2 and ActRIB, leads to the production of secreted
      TGFbeta antagonists that protect the anterior epiblast region from Nodal
      signalling.

PMID- 11291862
TI  - Roles of Sox factors in neural determination: conserved signaling in evolution?
AB  - Neural differentiation in amphibian embryos is initiated by the neural inducers
      emanating from the Spemann-Mangold organizer. The fate of uncommitted ectoderm is
      determined by graded BMP activity along the dorsal-ventral axis. Several
      transcriptional regulators acting in early neural differentiation have been
      identified, including Sox, Zic, Pou, HLH and Fox factors. In this paper, I review
      recent molecular studies on neural determination, focusing mainly on Sox factors.
      I also discuss the possible conservation of regulatory factors in neural
      differentiation, comparing Xenopus and Drosophila counterparts.

PMID- 11291863
TI  - Getting your head around Hex and Hesx1: forebrain formation in mouse.
AB  - An increasing amount of evidence suggests that in mouse there are two signalling
      centres required for the formation of a complete neural axis: the anterior
      visceral endoderm (AVE), and the node and its derivatives. Embryological and
      genetic studies suggest that the AVE has a head-inducing activity. In contrast,
      the node appears to act first as a head inducer in synergy with the AVE
      initiating anterior neural patterning at early stages of mouse development, and
      later, node derivatives are necessary for maintenance and embellishment of
      anterior neural character. Hex and Hesx1 are homeobox genes that are expressed in
      relevant tissues involved in anterior patterning. The analysis of the Hex and
      Hesx1 mutant mice has revealed that the lack of these genes has little or no
      effect on the early steps of anterior neural induction. However, both genes are
      required subsequently for the proper expansion of the forebrain region. We
      suggest that disturbance in the specification of an Fgf8 signalling centre in the
      anterior neural ridge may account for the anterior defects observed in these
      mutants.

PMID- 11291864
TI  - The role of Otx2 in organizing the anterior patterning in mouse.
AB  - Understanding the molecular mechanism controlling induction and maintenance of
      signals required for specifying anterior territory (forebrain and midbrain) of
      the central nervous system is a major task of molecular embryology. The current
      view indicates that in mouse, early specification of the anterior patterning is
      established at the beginning of gastrulation by the anterior visceral endoderm,
      while maintenance and refinement of the early specification is under the control
      of epiblast-derived tissues corresponding to the axial mesendoderm and rostral
      neuroectoderm. In vertebrates a remarkable amount of data has been collected on
      the role of genes contributing to brain morphogenesis. Among these genes,the
      orthodenticle group is defined bythe Drosophila orthodenticle and the vertebrate
      Otx1 and Otx2 genes, which contain a bicoid-like homeodomain. Mouse models and
      chimera experiments have provided strong evidence that Otx2 plays an important
      role in the specification and maintenance of the rostral neuroectoderm destined
      to become forebrain and midbrain. In evolutionary terms, some of these findings
      lead us to hypothesize a fascinating and crucial contribution of the Otx genes to
      the genetic program underlying the establishment of the mammalian brain.

PMID- 11291865
TI  - Defects of the body plan of mutant embryos lacking Lim1, Otx2 or Hnf3beta
      activity.
AB  - The orientation of the anterior-posterior (A-P) axis was examined in gastrula
      stage Hnf3beta, Otx2 and Lim1 null mutant embryos that display defective axis
      development. In situ hybridization analysis of the expression pattern of genes
      associated with the posterior germ layer tissues and the primitive streak (T,
      Wnt3 and Fgf8) and anterior endoderm (Cer1 and Sox17) revealed that the A-P axis
      of mutant embryos remains aligned with the proximo-distal plane of the gastrula.
      Further analysis revealed that cells which express Chrd activity are either
      absent in Hnf3beta mutant embryos or localised in heterotopic sites in Lim1 and
      Otx2 null mutants. Lim1-expressing cells are present in the Hnf3beta mutant
      embryo albeit in heterotopic sites. In all three mutants, Gsc-expressing cells
      are missing from the anterior mesendoderm. These findings suggest that although
      some cells with organizer activity may be present in the mutant embryo, they are
      not properly localised and fail to contribute to the axial mesoderm of the head.
      By contrast, in T/T mutant embryos that display normal head fold development, the
      expression domains of organizer, primitive streak and anterior endoderm genes are
      regionalised correctly in the gastrula.

PMID- 11291866
TI  - Otx2 and HNF3beta genetically interact in anterior patterning.
AB  - Patterning the developing nervous system in the mouse has been proposed to depend
      on two separate sources of signals, the anterior visceral endoderm (AVE) and the
      node or organizer. Mutation of the winged-helix gene HNF3beta leads to loss of
      the node and its derivatives, while mutation of the homeobox gene Otx2 results in
      loss of head structures, apparently at least partially because of defects in the
      AVE. To investigate the potential genetic interactions between the two signaling
      centers, we crossed Otx2+/- and HNF3beta+/- mice and found that very few Otx2+/
      ;HNF3beta+/- double heterozygous mutants survived to weaning. Normal Mendelian
      ratios of genotypes were observed during gestation, but more than half the double
      heterozygotes displayed a severe anterior patterning phenotype that would be
      incompatible with postnatal survival. The phenotype was characterized by varying
      degrees of holoprosencephaly, cyclopia with proboscis-like structures, and
      anterior forebrain truncations. Regional marker analysis revealed that ventral
      forebrain structures of Otx2+/-;HNF3beta+/- mutant embryos were most severely
      affected. Shh expression was completely absent in the anterior region of Otx2+/
      ;HNF3beta+/- embryos, suggesting that Otx2 and HNF3beta genetically interact,
      directly or indirectly, to regulate Shh expression in the anterior midline. In
      addition, the forebrain truncations suggest an involvement of both genes in
      anterior patterning, through their overlapping expression domains in either the
      AVE and/or the prechordal mesoderm.

PMID- 11291867
TI  - The isthmic organizer and brain regionalization.
AB  - Distinct neural identities are acquired through progressive restriction of
      developmental potential under the influence of local environmental signals.
      Evidence for the localization of such morphogenetic signals at specific locations
      of the developing neural primordium has suggested the concept of "secondary
      organizer regions", which regulate the identity and regional polarity of
      neighboring neuroepithelial areas one step further. In recent years, the most
      studied secondary organizer has been the isthmic organizer, which is localized at
      the hind-midbrain transition and controls anterior hindbrain and midbrain
      regionalization. Otx2 and Gbx2 expression is fundamental for positioning the
      organizer and for the establishment of molecular interactions that induce Fgf8
      expression and then, stabilize the autoregulative loop of En1, Wnt1 and Pax2
      expression. Temporospatial patterns of such gene expressions are necessary for
      the correct development of the organizer which, by a planar mechanism of
      induction, controls the normal development of the rostral hindbrain from r2 to
      the midbrain-diencephalic boundary. Fgf8 appears as the active diffusible
      molecule for isthmic morphogenetic activity and has been suggested to be the
      morphogenetic effector in other inductive activities revealed in other
      neuroepithelial regions.

PMID- 11291868
TI  - Early neurogenesis in Amniote vertebrates.
AB  - Labelling of Hensen's node in a 6-somite stage chick embryo by the quail/chick
      chimera method has revealed that, while moving caudalwards as the embryo
      elongates, the node leaves in its wake not only the notochord but also the floor
      plate and a longitudinal strand of dorsal endoderm. The node itself contains
      cells endowed with the capacity to yield midline cells (i.e. notochord and floor
      plate) along the whole length of the neural axis. Caudal node cells function as
      stem cells. They are responsible for the apical growth of the cord of cells that
      are at the origin of the midline structures since, if removed, neither the
      notochord nor the floor plate, are formed caudally to the ablation. The embryo
      extends however in the absence of midline cells and a neural tube develops
      posterior to the excision. Only dorsal molecular markers are detectable on this
      neural tube (e.g. Pax3 and Slug). The posterior region of the embryo in which the
      structures secreting Shh are missing undergo cell death within the 24 to 48 hours
      following its formation. Unpublished results indicate that rescue of the
      posterior region of the embryo can be obtained by implantation of Shh secreting
      cells. One of the critical roles of floor plate and notochord is therefore to
      inhibit the cell death programme in the axial and paraxial structures of the
      embryo at gastrulation and neurulation stages.

PMID- 11291869
TI  - Developmental biology of amphibians after Hans Spemann in Germany.
AB  - After the Hans Spemann and Hilde Mangold discovery of the importance of the
      dorsal blastopore lip for axis formation in the early embryo (Nobelprize for
      Spemann, 1935), the scientific community tried in a goldrush-like manner to find
      the inducing factors responsible for the programming of early embyronic
      determination and differentiation. The slow progress towards a solution of this
      problem caused a fading of interest on behalf of most laboratories. This article
      describes the activities of a few laboratories in Finland, Japan and Germany,
      which continued their studies despite tremendous experimental difficulties.
      Finally only Heinz Tiedemann's group in Berlin was the first which could isolate
      a mesoderm/endoderm inducing factor in highly purified form, the so-called
      vegetalizing factor, now known as activin. Furthermore this article describes the
      identification of neuralizing factors like Chordin, Cerberus and Dickkopf in the
      zone of the Spemann-Mangold organizer. The finding that BMP-4 acts as an
      antagonist to these factors located on the dorsal side led to a new understanding
      of the mechanisms of action of inducing (neuralizing) factors and early embryonic
      pattern formation. Moreover, the observations that closely related genes and
      their products were also found in Drosophila, Zebrafish, Mice and Human were the
      basis for new concepts of evolutionary mechanisms (dorsal/ventral and
      anterior/posterior polarity or conserved processes in eye-development of all 7
      animal phyla).

PMID- 11291870
TI  - Spemann's heritage in Finnish developmental biology.
AB  - The Finnish school of developmental biology can be considered a direct descendant
      of Spemann's school as both the original technology and the fundamental problems
      were introduced into Finland by Gunnar Ekman (1883-1937) who had worked for
      extended periods in Germany. After his early death, the work was continued by
      Sulo Toivonen (1909-1995), and until 1968 the group explored the mechanisms of
      primary induction and the subsequent segregation of the central nervous system.
      The extensive investigations led to the formulation of the "double-gradient"
      hypothesis and ultimately to its experimental vindication.

PMID- 11291871
TI  - Spemann's influence on Japanese developmental biology.
AB  - The discovery of the organizer by H. Spemann and Hilde Mangold, prompted a number
      of studies of embryonic induction in Japan. C.O. Whitman, N. Yatsu, T. Sato, H.
      Oka, T. Yamada, and Y.K. Okada were the pioneers in the field of embryonic
      induction. T. Yamada postulated the double potential theory for embryonic
      induction. O. Nakamura has modified the fate map of Vogt using newt and
      Xenopusblastulae. T.S. Okada and G. Eguchi proposed the new concept of
      "transdifferentiation" based on in vitro experiments in the retina and lens. T.S.
      Okada is not only an excellent scientist, but he has also nurtured many active
      developmental biologists. M. Takeichi, from his school, discovered the cell
      adhesion molecle, cadherin. Nakamura and colleagues tried to determine the origin
      and formation of the organizer. They performed recombination experiments using
      the ectoderm, endoderm and mesoderm, and concluded that the phenomenon in which
      various mesoderm tissues are formed by the recombination of the presumptive
      ectoderm with endoderm was "regulation of the vegetal-animal gradient". Some
      groups have also tried to purify specific inducing factors. T. Yamada and
      colleagues isolated two different types of ribonucleoproteins. I. Kawakami and
      colleagues showed that the ribosome fraction has neural inducing capacity, and
      that the extracellular matrix contains mesodermal inducing factors. Finally
      Asashima and colleagues isolated and identified activin A as a MIF factor. This
      finding had a great influence not only in the field of developmental biology, but
      also in molecular biology. Using activin, Asashima's group has successfully
      generated various organs, tissues, trunk-tail and head structures in vitro using
      animal caps (undifferentiated cells). Some other important molecules such as BMP,
      chordin and bFGF are also being studied by young Japanese scientists.

PMID- 11291872
TI  - Contribution of the Belgian school of embryology to the concept of neural
      induction by the organizer.
AB  - Albert BRACHET, founder of the Brussels School of embryology, conducted delicate
      experiments in which he selectively destroyed zones of the grey crescent with
      heated needles. This allowed him to observe, in 1923, that the median region of
      the grey crescent of the blastula is a area of spontaneous differentiation and
      that this "primary self-differentiation centre" organizes the axial organs in
      anurans. It is thus fair to say that A. BRACHET contributed significantly to the
      emergence of the organizer concept. Albert DALCQ and Jean PASTEELS, successors of
      A. BRACHET, trying to solve the problem of the organizer's determination,
      proposed their famous quantitative theory of embryonic development resulting in
      the concept of morphogenetic potential, which increases with the CV
      concentration, a combination of a cortical constituent C and a vegetal substance
      V. Jean BRACHET, the younger son of A. BRACHET and one of the founding father of
      molecular biology and embryology, was soon convinced that the organizer owes its
      inducing power to a chemical substance. Being the first to suggest the role of
      RNA in protein synthesis, he first imagined that RNA could be the active
      substance in induction but became convinced afterwards that the inducer must have
      a proteic nature. His interest in the molecular aspects of induction stimulated
      research that was to make chemical embryology molecular.

PMID- 11291873
TI  - Contrasting influences of the organizer and induction concepts on the scientific
      activity of French embryologists.
AB  - Unlike biologists from several European countries, most French embryologists did
      not work from the onset on problems associated with the Spemann-Mangold
      organizer, though they were fully aware of the importance of the discovery. They
      preferred to stay on other original topics, but their later work was of course
      influenced by the induction concepts. The exploration of secondary inductions in
      various organ formations was flourishing after 1950. As far as primary induction
      is concerned, two exceptions must be stressed: Vintemberger, who, before World
      War II, worked on the frog organizer for a few years, and especially Capuron
      (1968), who repeated Spemann and Mangold's fundamental experiment on a large
      scale. Then, from 1980 on, a series of studies dealing with the neural induction
      concept focused on studies of the gastrula ectoderm itself, was undertaken,
      mainly in Toulouse University by Duprat and her colleagues, and in Paris-6
      University by Boucaut and his colleagues.

PMID- 11291874
TI  - Consequences of the Spemann-Mangold organizer concept for embryological research
      in Russia: personal impressions.
AB  - The impact of the organizer concept on Russian experimental embryology is shortly
      reviewed. Attempts to study embryonic induction in Russia may be grouped into
      embryological and biochemical approaches. This paper provides a framework for,
      and overvalue of, the contributions of Russian biologists to the problem of
      embryonic induction. Two model systems--lens and neural inductions--are of
      special significance to modern developmental biologists. Moreover, the study of
      eye lens induction actually gave rise to research on developmental mechanics in
      Russia. This was one of the reasons why we limited this article to these two
      model systems. After retrospective consideration of the results of the search for
      possible lens-inducing factor candidates, the discussion turns towards some of
      the examples of neural-inducing agents detected in embryonic tissues and the new
      questions raised by the progress that has been made in the analysis of the
      Spemann-Mangold organizer.

PMID- 11291875
TI  - The organizer concept and modern embryology: Anglo-American perspectives.
AB  - This paper analyses the origins of the Spemann-Mangold organizer concept of 1924
      in relation to his earlier background and concepts. It traces the consequences
      and fate of the organizer, and related concepts (embryonic induction, gradients,
      fields) through subsequent phases in the evolution of developmental biology up to
      the present, primarily from a UK perspective, but also in the USA. The origins of
      Wolpert's concept of positional information of around 1970 are analysed; this
      markedly different model of embryogenesis effectively took the place of the
      organizer, following on from a generally assumed out-datedness of the corpus of
      Spemann's data and concepts. Explanations in terms of historical forces are
      suggested; events are seen as a historical causal chain. A crucial factor appears
      to have been the long-term neglect of morphogenetic cell movement as an integral
      component of an adequate induction-based model. The paper discusses the general
      inter-relation of history and science, and particularly the implications for
      current scientific practice, including the potential for conceptual distortions
      due to historical factors. It is argued that historical considerations need to be
      included as part of the use and critical assessment of basic concepts in science.

PMID- 11291876
TI  - Microwave coagulation therapy for liver cancer: laparoscopic microwave
      coagulation.

PMID- 11291877
TI  - Ecabet sodium inhibits the ability of Helicobacter pylori to induce neutrophil
      production of reactive oxygen species and interleukin-8.
AB  - The pathogenic role of human neutrophils has been implicated in Helicobacter
      pylori-associated gastritis. Ecabet sodium, a locally acting antiulcer drug, has
      anti-H. pylori actions. The aim of this study was to examine the effects of
      ecabet on the ability of H. pylori to stimulate human neutrophils. H. pylori were
      added to 1 x 10(5) neutrophils and incubated for 30 min in the presence of
      ecabet. Bacterial suspensions which had been incubated with ecabet for 30 min
      were also used to stimulate neutrophils. The intracellular production of reactive
      oxygen species was measured with a FACScan. Bacterial suspensions were also added
      to neutrophils in the presence of ecabet and incubated at 37 degrees C for 12 h
      to measure interleukin (IL)-8 production by enzyme-linked immunosorbent assay.
      The mean fluorescence intensity was found to be attenuated dose-dependently by
      ecabet (P < 0.01). Ecabet also inhibited IL-8 production by neutrophils in a dose
      dependent manner (P < 0.001). Bacteria with prior incubation with ecabet induced
      significantly lower IL-8 production than those without this incubation (P <
      0.05). Ecabet sodium has preventive effects on the ability of H. pylori to
      stimulate human neutrophils. It may lead to reduced gastritis activity and
      decreased oxidative damage of the gastric mucosa in H. pylori-associated
      gastritis.

PMID- 11291878
TI  - Macroscopic typing with wall stricture sign may reflect tumor behaviors of
      advanced colorectal cancers.
AB  - No appropriate macroscopic classification of advanced colorectal cancers (A-CRC)
      is available for assessing their tumor behavior. In the present study, A-CRC were
      classified macroscopically as either stricture or nonstricture type, and the
      differences in clinicopathological features, mode of recurrence, and prognosis
      between the two types were investigated. The subjects were 166 patients with A
      CRC invading beyond the muscular layer who had undergone curative surgical
      resection. Fresh resected specimens from these patients were used for the study.
      The A-CRC were classified as of stricture or nonstricture type according to
      whether or not they showed marked fold convergence and/or stricture of the
      intestinal tract (more than 30% wall shrinkage) that had the appearance of a "bow
      tie". Of the 166 A-CRC, 47 (28%) were classified as stricture type. This type was
      significantly more frequent in the colon (37%; 37/101) than in the rectum (15%;
      10/65) (P = 0.003). The stricture type was more frequently associated with an
      abundance of fibrosis than the nonstricture type (76%; 28/37 vs 39%; 25/64 in
      colon; P < 0.001; 100%, 10/10 vs 42%, 23/55 in rectum; P < 0.001). The recurrence
      rate was also higher in the stricture type than in the non-stricture type in both
      the colon (51%, 19/37 vs 17%, 11/64; P = 0.003) and rectum (80%, 8/10 vs 38%,
      21/55; P = 0.01). The time to recurrence was significantly shorter for the
      stricture type in both the colon (P < 0.001) and rectum (P = 0.02). These results
      indicate that the macroscopic typing of A-CRC according to the presence or
      absence of wall stricture sign may reflect their tumor behavior, although this
      behavior appears to be complex and related to tumor progression. This
      classification could be important clinically to assess tumor behavior in a simple
      way.

PMID- 11291879
TI  - Circulating sialyl Lewis(x), sialyl Lewis(a), and sialyl Tn antigens in
      colorectal cancer patients: multivariate analysis of predictive factors for serum
      antigen levels.
AB  - Preoperative serum levels of sialyl Lewis(a) (CA 19-9), sialyl Lewis(x) (SLX),
      and sialyl Tn (STN) antigens in colorectal cancer patients were examined to
      establish predictive factors for serum levels of these antigens compared with
      carcinoembryonic antigen (CEA). A total of 308 patients who underwent resection
      for a colorectal cancer were divided into low and high antigen groups (higher or
      lower than a selected diagnostic-based cutoff value). The cutoff values were 37
      U/ml for CA19-9, 38 U/ml for SLX, 45 U/ml for STN, and 2.5 ng/ml for CEA. The
      American Joint Committee on Cancer Classification and Stage grouping was used to
      classify the tumors. Statistical tests were conducted using univariate and
      multivariate logistic regression analyses. For CA19-9, 81 patients (26.3%) were
      assigned to the high antigen group: for SLX, 39 (12.7%); for STN, 33 (10.7%); and
      for CEA, 133 (43.2%). Multivariate logistic regression analysis revealed that
      predictive factors associated with high antigen levels were female sex (odds
      ratio [OR], 1.78 vs male sex), T4 (OR, 3.26 vs T1/T2), and M1 (OR, 3.35 vs M0)
      for CA19-9; M1 (OR, 6.40 vs M0) for SLX; mucinous carcinoma (OR, 8.45 vs well
      differentiated adenocarcinoma) and M1 (OR, 8.24 vs M0) for STN; and mucinous
      carcinoma (OR, 7.21 vs well differentiated adenocarcinoma), T3/T4 (OR, 3.84/4.18,
      respectively, vs T1/T2), and M1 (OR, 6.39 vs M0) for CEA. In conclusion, high
      serum levels of CA19-9, SLX, and STN are strongly associated with distant
      metastasis. In addition, high serum levels of CA19-9 may be an independent
      predictor for female gender and T4, and high serum levels of STN may be an
      independent predictor for mucinous carcinoma.

PMID- 11291880
TI  - Effectiveness of endoscopic biliary drainage for unresectable hepatocellular
      carcinoma associated with obstructive jaundice.
AB  - Endoscopic biliary drainage (EBD) for unresectable hepatocellular carcinoma (HCC)
      associated with obstructive jaundice remains controversial because of the short
      survival of these patients. To evaluate the effectiveness of this procedure, we
      retrospectively studied 18 patients who had unresectable HCC with obstructive
      jaundice and underwent EBD with polyethylene stents, over a 10-year period. Nine
      patients with tumor thrombus involving the first branches of the portal vein or
      portal trunk (Vp3) formed group A and the other 9 (Vp0-Vp2) formed group B. The
      serum albumin level and serum total bililubin level differed significantly
      between the two groups (P < 0.05 and P < 0.005. Student's t-test), but
      prothrombin time did not. The obstructive jaundice was mainly caused by direct
      tumor invasion in 6 patients from group A and 3 from group B, by blood clots
      and/or tumor fragments in 2 patients from group A and 3 from group B, by the
      tumor protruding into the common hepatic duct in 2 patients from group B. and by
      tumor compression of the common bile duct in 1 patient from each group. Drainage
      was successful in 4 patients (44%) from group A and in all 9 patients (100%) from
      group B. Among the 5 patients with unsuccessful drainage in group A, 4 had
      obstruction of both the left and right hepatic ducts and 3 had multiple tumors in
      both lobes. The mean survival time (mean +/- SD) after EBD was 47 +/- 44 days in
      group A and 181 +/- 70 days in group B. In group A. the average survival time was
      only 85 days in the 4 patients with successful drainage. However, an improvement
      in the quality of life after EBD was observed in one-third of the Vp3 patients
      and in all of the Vp0-Vp2 patients. In summary, satisfactory palliation is
      possible with successful EBD, but this is difficult in most patients with Vp3
      portal thrombus, direct tumor invasion involving both hepatic ducts, and multiple
      tumors in both lobes. It is important to determine the site, extent, and nature
      of the obstruction, as well as liver function and the presence of portal
      thrombus, before performing EBD.

PMID- 11291881
TI  - Portopulmonary hypertension: distinctive hemodynamic and clinical manifestations.
AB  - Portopulmonary hypertension is now recognized as one of the pulmonary
      complications of chronic liver disease. However, previous studies reported that
      the incidence ranged from 0.25% to 2%, excluding fortuitous coincidence. In this
      study, we aimed to determine the variant hemodynamic and clinical features of
      portopulmonary hypertension in an area with a high prevalence of viral cirrhosis.
      After reviewing the hemodynamic data of 322 patients with portal hypertension
      admitted to the Taipei Veterans General Hospital between 1987 and 1999, we found
      10 with portopulmonary hypertension. The overall incidence was, therefore, 3.1%
      in all patients with portal hypertension. Most of the patients with
      portopulmonary hypertension experienced exertional dyspnea. The survival times
      ranged from 2 to 86 months. In our series, most of the patients who died, died of
      complications related to cirrhosis and portal hypertension, but not of
      complications related to pulmonary hypertension. This study suggested that
      portopulmonary hypertension was not a frequent complication in cirrhotic patients
      and was not associated with an adverse outcome.

PMID- 11291882
TI  - Importance of precise timing in the simplified 10-min 14C-urea breath test
      procedure.
AB  - This study was performed to assess the impact of precise timing and the
      repeatability of the simplified 10-min 14C-urea breath test. Thirty-three
      patients underwent a 14C-urea breath test at 10 and 12 min (test I) and after 24
      h (test II). The paired t-test was applied to assess differences between two
      successive measurements at 10 and 12 min, and the method of Bland and Altman was
      used to evaluate the repeatability of the test. Only test I (P = 0.004) showed a
      significant difference between two successive measurements at 10 and 12 min. The
      coefficients of repeatability at 10 and 12 min were 1.54 and 1.48, respectively.
      No bias was found. From this study, we can conclude that breath collections,
      delayed by 2 min (20% error), have no impact on the clinical interpretation of
      the results. The repeatability of the simplified 10-min 14C-urea breath test is
      sufficient for clinical use.

PMID- 11291883
TI  - Gastric T-cell lymphoma presenting with epithelioid granulomas mimicking
      tuberculosis in regional lymph nodes.
AB  - In patients with malignant lymphomas, a sarcoid reaction is occasionally
      observed. However, lymphoma-related granulomas with caseous necrosis are rare. We
      describe such a case of T-cell gastric lymphoma that was difficult to diagnose. A
      50-year-old man was referred to our hospital because of abnormal gastric
      endoscopic findings: hypertrophic folds with narrowing of the gastric lumen and
      multiple ulcers in the body. Gastric biopsy specimens showed non-specific
      inflammation. An open biopsy of the enlarged gastric regional lymph nodes was
      performed. The sections revealed effacement of the normal architecture and
      replacement by numerous epithelioid granulomas accompanied by Langhan's type
      giant cells with or without central caseous necrosis, strongly suggesting
      tuberculosis. However, mycobacteria and other causative organisms were not
      detected, and an anti-tuberculous regimen was ineffective. Repeat gastric
      biopsies were performed and, finally, atypical lymphocytes were observed
      infiltrating the mucosa. The patient was diagnosed with gastric T-cell lymphoma
      based on the results of immunohistochemical stainings. After chemotherapy, a
      total gastrectomy was performed. The diagnosis of gastric T-cell lymphoma with a
      sarcoid reaction was confirmed by histological findings of the sections. Namely,
      the gastric wall was replaced by atypical lymphocytes showing the phenotype of
      helper T cells, admixed with epithelioid granulomas with Langhan's type giant
      cells. Thus, this case suggests that regional lymph nodes in gastric lymphomas
      may be present as epithelioid granulomas with caseous necrosis, mimicking
      tuberculosis.

PMID- 11291884
TI  - Primary adenocarcinoma of the duodenum demonstrated by ultrasonography.
AB  - A 57 year-old man presented with abdominal discomfort and melena. Abdominal
      ultrasonography clearly revealed a duodenal tumor as a hypoechoic mass in the
      transverse segment of the duodenum. The lesion was a 4 x 4-cm oval mass with
      partial concavity, an irregular surface, high-level central echoes, and a
      hypoechoic periphery. After confirmation of the diagnosis of duodenal carcinoma,
      a pylorus-preserving pancreatoduodenectomy was performed curatively. Pathological
      examination revealed moderately differentiated tubular adenocarcinoma partially
      invading the pancreatic parenchyma. Ultrasonography can be used to detect lesions
      of the transverse segment of the duodenum as the first imaging procedure.

PMID- 11291885
TI  - Reappearance of HBsAg with compartmentalized different HBV strains in allograft
      versus PBMC of the recipient.
AB  - A woman who was positive for anti-hepatitis B surface antigen (anti-HBs) and anti
      hepatitis B core antigen (anti-HBc) received an orthotopic liver transplantation
      from an anti-HBc-seropositive donor in November 1985. Reappearance of hepatitis B
      surface antigen (HBsAg) was noted 5 months after the transplantation, but it was
      not associated with significant liver inflammation. Ten years after the
      transplantation, results of serum hepatitis B virus (HBV) DNA study, by nested
      polymerase chain reaction, were negative. However, HBV DNA was detected in the
      transplanted liver tissues and peripheral blood mononuclear cells. Different
      strains were identified in these two organs. An adw strain was found in the
      transplanted liver, whereas an adr strain with long segment deletions in the core
      gene was found in the peripheral blood mononuclear cells. Covalently closed
      circular HBV DNA was not detected in any of the tissues examined. Occult HBV
      infection in the donor as well as the recipient is common in HBV endemic areas.
      The recipient in this case had reappearance of hepatitis B surface antigen
      (HBsAg) in the serum after transplantation. Nevertheless, 10 years later, two
      different strains of HBV were identified in different organs, without cross
      infection. The present case demonstrates that HBsAg reappearance was not
      associated with reactivation of the virus and liver inflammation. This type of
      HBsAg reappearance did not appear to produce a significant hazard to the
      transplanted liver.

PMID- 11291887
TI  - How can we prevent viral reactivation in liver transplantation from donors with
      latent hepatitis B virus infection?

PMID- 11291886
TI  - Focal nodular hyperplasia coexistent with hemangioma and multiple cysts of the
      liver.
AB  - We report here a case of hepatic focal nodular hyperplasia (FNH) associated with
      hepatic hemangioma and multiple hepatic cysts in a 71-year-old man. He was
      admitted to our hospital because of body weight loss. Ultrasonography detected
      multiple cysts. and two tumors in the liver one, 3.5 cm and one, 1.6 cm. Color
      Doppler ultrasonography showed arterial signals within the large tumor. On
      dynamic computed tomography, the large tumor was a hypodense lesion which was
      enhanced during the arterial phase and almost isodense during the delayed phase:
      the small tumor was also a hypodense lesion, and was enhanced during both the
      arterial and delayed phases. On magnetic resonance imaging using
      superparamagnetic iron oxides, the large tumor had decreased signal intensity on
      the T2-weighted image. On hepatic arteriography, the feeding artery of the large
      tumor showed a spoke-wheel appearance and that of the small tumor showed a cotton
      wool appearance. Ultrasonographically guided fine-needle aspiration biopsy of the
      large tumor revealed hepatocellular hyperplasia. Finally, we diagnosed the two
      hepatic tumors as FNH and hemangioma. There was no intracranial lesion. The cause
      of the patient's emaciation was psychogenic anorexia. To our knowledge, this is
      the first case report that describes the simultaneous occurrence of these three
      kinds of hepatic lesions. The pathogenesis of FNH still remains unclear, but this
      association suggests that FNH may arise because of a vascular anomaly.

PMID- 11291888
TI  - Idiopathic thrombocytopenic purpura complicated with asymptomatic primary biliary
      cirrhosis.

PMID- 11291889
TI  - Information for social work practice: observations regarding the role of the
      World Wide Web.

PMID- 11291890
TI  - Mental quality of life: an indicator of unmet needs in patients with diabetes.
AB  - This exploratory study investigates the quality of life needs of 173 individuals
      being treated for type 2 diabetes over a six month period of time. It samples
      patients whose primary care providers practice the most current model for
      delivering care, diabetes disease management. These physicians utilized a
      multidisciplinary diabetes education program to facilitate the patient-provider
      knowledge-based partnership essential in discase management. Patient quality of
      life changes were measured by the SF-36. A paired samples t-test showed
      significant diminishment in patients' mental quality of life indicating
      diminished overall emotional functioning, negatively impacting quality of life;
      possibly due to the effects of time. Multiple regression results also indicated
      that patients at risk for major depression and at risk for major depression
      superimposed on dysthymia experienced significantly diminished mental quality of
      life. These findings suggest that enhanced mental health assessment and mental
      health services provided by social workers in diabetes education programs and/or
      primary care settings would improve patient mental quality of life.

PMID- 11291891
TI  - Selecting a measure of health related quality of life.
AB  - Quality of life is becoming recognized increasingly as an important outcome
      measure which needs to be considered by social workers. However, there does not
      appear to be a clear consensus about the definition of quality of life. In
      addition, social workers are likely to experience difficulties choosing and
      applying an appropriate instrument with which to measure quality of life because
      of the many available instruments purporting to assess quality of life. This
      paper discusses the definition of health-related quality of life and explains the
      main measurement properties of an instrument that must be appraised when
      considering whether or not an instrument is appropriate. The paper will assist
      social workers to make an informed choice about measures of health-related
      quality of life.

PMID- 11291892
TI  - An evaluation of a psychotherapeutic group intervention for persons having
      difficulty coping with musculoskeletal disorders.
AB  - This study evaluated an 8-9 week psychotherapeutic group program designed to help
      people cope with the difficulties and changes that arise when living with
      musculoskeletal (MSK) disorders. Also examined were individual differences in
      client expectations about the benefits of the groups. Participants were 64
      community-dwelling adults who completed questionnaires at the beginning, end, and
      three months after their final group session. Outcomes were mastery, coping
      efficacy, helplessness, self-acceptance and depression. Significant changes from
      pre- to post-intervention were found in mastery, depression, and coping-efficacy
      with effect sizes of .50 or greater. Individuals who had concerns or reservations
      about participating in the groups gained from the intervention in the same ways
      as others who were more positive at the outset of the groups.

PMID- 11291893
TI  - Young women with PD: a group work experience.
AB  - Parkinson's Disease (PD) prior to the age of 40 affects between 5-10% of the PD
      population. The psychosocial changes that patients with early PD encounter, may
      be more devastating and disabling than the actual motor disability. The paper
      describes a unique experience in groupwork with young female PD patients treated
      in the Movement Disorders Unit of the Tel Aviv Sourasky Medical Center. The paper
      focuses on the special issues which characterized this group's experience:
      stigma, body and sexual image, and personality traits.

PMID- 11291894
TI  - A Department of Social Work uses data to prove its case [corrected].
AB  - The introductions of managed care with its emphasis on cost containment has led a
      Department of Social Work Services at a large urban teaching center to better
      document and justify its roles. A concrete result was the saving of social work
      positions during budget cutbacks and downsizing. There is also information in
      these data to help clarify the differential roles of social workers and
      utilization review nurses in the hospital case management/discharge planning
      processes. The system came about because of concerns around cost containment, the
      need for more systematic discharge planning and the advent of the Prospective
      Payment System and Diagnosis Related Groups (DRG's) as a means of reimbursement
      to hospitals.

PMID- 11291895
TI  - Elimination of cataract blindness: a global perspective entering the new
      millenium.

PMID- 11291896
TI  - Serving children, youth, and families with alcohol and other drug-related
      problems in child welfare.

PMID- 11291897
TI  - Substance abuse and child welfare: clear linkages and promising responses.
AB  - Parental substance abuse is a significant factor in many of the families served
      in the child welfare system. This article examines: (1) the prevalence of
      substance abuse among families involved with the child welfare system; (2) the
      impact of substance abuse on child welfare practice; (3) how both the Adoption
      and Safe Families Act of 1997 and welfare reform legislation intensify the need
      to address parental substance abuse effectively; and (4) promising strategies for
      addressing these families' needs.

PMID- 11291898
TI  - Combining child welfare and substance abuse services: a blended model of
      intervention.
AB  - Montgomery County, Maryland's Child Welfare Services (CWS) and Adult Addiction
      Services (AAS) developed an initiative to address the requirements of the
      Adoption and Safe Families Act (ASFA) while meeting the needs of families and the
      community of providers. A blended model of intervention was determined to be the
      best strategy to achieve the dual mandates of CWS and alcohol and other drugs
      (AOD) providers. Drawing from criminal justice, systems theory, social work, and
      addiction treatment, the approach made use of graduated sanctions or levels of
      intensity in providing services, engaging client participation, and engendering
      motivation. This article proposes strategies at client and organizational levels
      to understand the process of adaptation to ASFA and to guide planning for
      blending services.

PMID- 11291899
TI  - Caregiver AOD use, case substantiation, and AOD treatment: studies based on two
      southwestern counties.
AB  - This article includes two separate studies: the first explores the impact of
      caregiver AOD use on CPS case substantiation; the second compares CPS-involved
      and CPS-noninvolved females in AOD treatment systems. Results suggest that cases
      with indications of AOD use are more likely to be substantiated than cases
      without; and increasing numbers of children and younger maternal ages are risk
      factors for CPS involvement among AOD-using women. Related findings are also
      presented, followed by implications for practice and research.

PMID- 11291900
TI  - Residential substance abuse treatment for pregnant and postpartum women and their
      children: treatment and policy implications.
AB  - In FY 1993 and FY 1995, the federal government awarded 27 five-year grants that
      supported 35 residential treatment projects for substance-abusing pregnant and
      postpartum women and their children. These projects provided comprehensive
      culturally and gender-specific treatment. Preliminary aggregated data collected
      in a national cross-site evaluation of 24 of these projects are encouraging with
      respect to infant mortality and morbidity, treatment retention and completion
      rates, and behavioral changes in the participating mothers at six months
      postdischarge. Local evaluations reflect other benefits of treatment. Cost data
      are expected to demonstrate the efficiencies and benefits of these projects
      compared to no treatment.

PMID- 11291901
TI  - Treating substance-using women and their children in public housing: preliminary
      evaluation findings.
AB  - The Key West Housing Authority created SafePort, a residential substance abuse
      treatment program within public housing to provide drug treatment to parenting
      women. All family members-women, children, and significant others-receive
      comprehensive assessments to determine appropriate therapeutic interventions to
      resolve their problems. Preliminary evaluation findings suggest that women who
      participate with their children are more likely to remain drug free than are
      those who participated without their children.

PMID- 11291902
TI  - Parenting services for families affected by substance abuse.
AB  - This article describes the development, implementation, and replication of a
      group-based parenting program for families affected by substance abuse. The
      Nurturing Program for Families in Substance Abuse Treatment and Recovery improves
      parenting, as measured on objective scales; enhances parents' satisfaction and
      competence, as measured by participant reports; and is based on principles
      demonstrated to be effective in reducing risk of both child abuse and neglect and
      substance abuse for both parents and children.

PMID- 11291903
TI  - Parental substance abuse and the development of children in family foster care.
AB  - To determine the impact of parental substance abuse on children, the cognitive
      skills and behavior ratings of 268 school-age children placed in family foster
      care were examined. As a group, the children in family foster care presented with
      low average cognitive skills and made significant improvement in cognitive
      functioning during placement. The children with prenatal exposure to drugs scored
      significantly lower in cognitive skills at the beginning of placement but made
      significantly more progress than the other children during placement. Behavior
      ratings by the foster parents and teachers revealed that 29% of the children had
      scores in the significant range, and the children exposed prenatally to drugs had
      a higher incidence of behavior problems at school compared to family foster care
      peers. Recommendations for further study of these factors and for enhancing
      outcomes for children in care are provided.

PMID- 11291904
TI  - The role of spirituality in the recovery process.
AB  - Though innovative approaches to working with substance-abusing parents of
      maltreated children have emerged within the last few years, child welfare
      agencies continue to be challenged by the chronic nature of addictive diseases.
      This article discusses the often ignored element of spirituality as a critical
      component of recovery for parents. It also highlights how the regulation of
      spirituality by parents has a significant influence on their ability to
      responsibly care for their children.

PMID- 11291905
TI  - Research outcomes of prenatal substance exposure and the need to review policies
      and procedures regarding child abuse reporting.
AB  - Research on the outcomes of drug-exposed children evinces elevated developmental
      risks from the interaction of subtle biological vulnerabilities and compromised
      parenting. States, however, have generally not reviewed the procedures and
      policies they developed in the early 1990s when there was less research and
      experience with these children. At that time the gravest risks related to
      perinatal substance exposure seemed to be excessively punitive treatment of
      mothers by over-zealous criminal justice prosecutors. This article clarifies
      policy options for reporting and serving children who are born testing positive
      for controlled substances and also calls for strengthening existing state
      policies regarding child abuse reporting and response.

PMID- 11291906
TI  - Assessing progress against the size of the problem.
AB  - To summarize articles with the depth and range of the nine in this collection is
      difficult. What the articles demonstrate as a whole is that a great deal of
      activity is under way in the arena of connecting child welfare and substance
      abuse services, with a growing body of documentation accompanying it. The
      articles bode good news in that they indicate a broadening awareness of the
      interconnectedness of these issues, and they highlight a number of creative and
      effective programs that have been established to mitigate the problems.
      Tremendous challenges-from funding to outcomes research-however, are also made
      evident in this body of work.

PMID- 11291907
TI  - Adaptation of the hypoosmotic swelling test to assess functional integrity of
      stallion spermatozoal plasma membranes.
AB  - Hypoosmotic swelling (HOS) is used for assessing plasma membrane function and
      fertilizing capacity of human spermatozoa. However, HOS solutions and
      methodologies have not been evaluated specifically for assessing stallion
      spermatozoa. The objective of this study was to identify a HOS solution and assay
      conditions specifically for stallions that would maximize spermatozoal plasma
      membrane swelling. The HOS solutions and assay conditions, including incubation
      time (15 to 180 min), temperature (25 degrees vs 37 degrees C), and total number
      of cells examined (100, 200 or 500) were evaluated. Assay consistency, accuracy,
      reliability and repeatability also were determined. Maximum spermatozoal plasma
      membrane swelling was observed in a 100 mosmol sucrose solution (P < 0.001).
      Incubation time (P = 0.67), temperature (P = 0.70) and total number of
      spermatozoa examined (P = 0.38 and P = 0.24 for 100 vs 200 and 100 vs 500,
      respectively) did not influence percent of HOS positive spermatozoa observed. A
      high degree of assay accuracy was indicated when a correlation of r = 0.998 was
      obtained between the HOS positive spermatozoa observed and expected when known
      amounts of heat-treated spermatozoa, unable to undergo swelling, were added to
      untreated spermatozoa. Assay consistency was demonstrated, as reflected by a mean
      coefficient of variation of 0.073 for 4 stallions. Also, the coefficient of
      variation from 2 analyses of variance was 0.168 and 0.096, indicating reasonably
      good assay reliability; estimates of repeatability from the same analyses were
      0.794 and 0.968. The HOS test adapted to stallion spermatozoa in this study is a
      simple, highly accurate and consistent assay with good reliability and
      repeatability. Results observed under the conditions evaluated also permit some
      flexibility in adapting this assay to individual laboratory and practice settings
      for evaluating stallion spermatozoal plasma membranes.

PMID- 11291908
TI  - Uterine secretion from mares with post-breeding endometritis alters sperm motion
      characteristics in vitro.
AB  - Uterine secretion was collected from five normal mares during estrus by the use
      of a tampon. In subsequent estrus cycles, mares were inseminated with 1 x 10(9)
      spermatozoa from a stallion of known fertility, and uterine secretion was
      collected randomly at 6, 12, and 24 hours after insemination. All mares had
      negative endometrial cytology before insemination. At the time of uterine
      secretion sampling, semen was collected from two stallions and extended with
      Kenney's extender to a concentration of 50 x 10(6) spermatozoa/mL. Extended semen
      was diluted 2:1 with uterine secretion; semen extender; and centrifuged uterine
      secretion (noncellular). Samples were kept at room temperature and sperm motion
      characteristics (corrected motility (CMOT), progressively motile spermatozoa
      (PMS), and mean path velocity (MPV) were evaluated using a computer-assisted
      semen analyzer every 40 minutes for a total of 4 hours. Sperm motion
      characteristics of spermatozoa were significantly better when incubated in semen
      extender compared to uterine secretion (P < 0.05). The CMOT and PMS were
      significantly better in uterine secretion collected before, compared to after AI
      with the lowest values observed in samples collected at 12 hours after breeding
      (P < 0.05). Sperm motion characteristics of spermatozoa incubated in centrifuged
      uterine secretion was only slightly suppressed compared to spermatozoa incubated
      in semen extender, suggesting that the altered motion characteristics were mostly
      due to the presence of polymorphonuclear neutrophils (PMNs) in the samples. It
      was concluded from this study that spermatozoa can survive in inflamed uterine
      secretion, but that sperm motion characteristics in vitro are altered.

PMID- 11291909
TI  - Ultrasonic study of follicular dynamics following superovulation in German Merino
      ewes.
AB  - Ewes are commonly superovulated with a single dose of eCG or multiple doses of
      pFSH. It would be convenient and less expensive to use a single dose of FSH, but
      results of various trials have been controversial. We wished to investigate
      ovarian dynamics using ultrasonography after superovulation with a single dose of
      pFSH and hMG as compared with a single dose of eCG. Estrus was synchronized
      during the breeding season with fluorogestone acetate-containing intravaginal
      sponges in adult German Merino ewes (n = 38). They were superovulated with single
      doses of pFSH (17 mg; n = 10), hMG (600 IU FSH and 600 IU LH; n = 9) or eCG (1250
      IU; n = 10) given at the time of sponge removal, or pFSH (17 mg; n = 9) given 36h
      before sponge removal. Follicular and luteal development were observed by
      ultrasonic scanning every 8 h from the gonadotrophin injection until the end of
      estrus, and then once daily until Day 6 after estrus. Jugular venous blood was
      collected starting immediately before and 1 h after superovulation treatment,
      then twice daily until the end of estrus and once daily for the following 7 days.
      Concentrations of estradiol-17beta (E2) and progesterone (P4) were measured in
      plasma. Differences in the follicular dynamics of the 4 superovulation groups
      were obvious. The functional duration of the pFSH action was estimated to last
      approximately 48 h, whereas eCG and hMG were active for up to 72 h. The diameter
      of the ovulatory follicles proved to be smaller than it was described for
      unstimulated ewes. Single applications of pFSH or hMG can induce a superovulatory
      response, although the post-estrus progesterone profile revealed a high premature
      luteal regression rate in the different superovulation groups. Premature corpus
      luteum regression could not be seen by ultrasonography at this early stage of the
      luteal phase, indicating that the technique may fail to detect these corpora
      lutea in an embryo transfer program. However, ultrasonography represents a
      suitable method to observe follicular dynamics following different superovulation
      regimens in sheep.

PMID- 11291910
TI  - Effects of cysteamine, fsh and estradiol-17beta on in vitro maturation of porcine
      oocytes.
AB  - Porcine cumulus-oocyte complexes (COCs) were cultured for 48 h with addition or
      absence of exogenous estradiol-17beta (E2; 1 microg/mL) in the maturation medium
      (mM199). The medium was supplemented with sodium pyruvate (0.1 mg/mL), 10% (v/v)
      FCS, various concentrations of FSH (0, 1 and 10 microg/mL) and with or without
      cysteamine (150 microM). When supplemented with E2, cysteamine enhanced the rates
      of germinal vesicle breakdown (GVBD) and maturation to metaphase-II (M-II) in
      COCs cultured in the medium with 0 and 1 microg/mL FSH (P<0.05). Among COCs
      cultured with FSH, oocytes cultured with 1 microg/mL FSH and E2 but without
      cysteamine showed the lowest rates of GVBD and M-II. The rates were, however,
      significantly increased when cysteamine was added to the same medium or by
      increasing FSH concentration to 10 microg/mL in the maturation medium. E2
      significantly inhibited the rates of GVBD and M-II in COCs cultured without FSH
      and cysteamine (a group of oocytes with spontaneous maturation). When COCs were
      cultured in TCM 199 with 1 or 10 microg/mL FSH, with or without E2 (1 microg/mL)
      and fertilized in vitro, the rates of male pronucleus formation were not
      increased by increasing FSH concentration, but the addition of cysteamine to the
      maturation medium significantly enhanced the rates in the same FSH treatment. The
      results indicate that E2 inhibits spontaneous GVBD and maturation to M-II of
      porcine oocytes and that a low concentration of FSH (1 microg/mL) is not
      sufficient to induce full nuclear maturation, compared with 10 microg/mL FSH, but
      that it can complete nuclear maturation with cysteamine and E2. However, the
      cytoplasmic maturation is promoted only by the addition of cysteamine in the
      medium.

PMID- 11291911
TI  - Behavioral and endocrine responses of hair sheep ewes exposed to different mating
      stimuli around estrus.
AB  - Hair sheep ewes were used to evaluate the influence of various levels of mating
      stimuli on the duration and timing of estrus and LH concentrations around estrus.
      Ewes were treated with PGF2alpha (15 mg, im) 10 d apart. At the time of the
      second PGF2alpha treatment (Day 0) ewes were placed in groups and exposed to
      different types of mating stimuli. One group of ewes (n = 16) was exposed to an
      epididymectomized ram (RAM), a second group of ewes (n = 16) was exposed to an
      epididymectomized ram wearing an apron to prevent intromission (APRON) and a
      third group of ewes (n = 17) was exposed to an androgenized ovariectomized ewe (T
      EWE). Jugular blood samples were collected from ewes at 6-h intervals through Day
      5. Plasma was harvested and LH concentration was determined by RIA. The ewes were
      observed at 6-h intervals to detect estrus. A ewe was considered to be out of
      estrus when she no longer stood to be mounted by the teaser animal. There was no
      difference (P > 0.10) in the proportion of ewes expressing estrus (79.6%) or
      having an LH surge (85.7%) among the treatments. Neither the time to estrus nor
      the duration of estrus were different (P > 0.10) among APRON, RAM or T-EWE groups
      (41.6+/-3.8 vs 43.6+/-3.6 vs 46.1+/-3.6 h, respectively, and 26.5+/-2.2 vs 24.8+/
      2.3 vs 30.5+/-2.2 h, respectively). The time to LH surge was similar (P > 0.10)
      among APRON, RAM and T-EWE groups (51.2+/-4.5 vs 51.2+/-4.7 vs 52.7+/-4.5 h,
      respectively). The magnitude of the LH surge was similar (P > 0.10) in the T-EWE,
      APRON and RAM ewes (99.7+/-4.9 vs 87.2+/-4.9 vs 85.8+/-5.0 ng/mL, respectively).
      The time from estrus to the LH surge was not different (P > 0.10) among APRON,
      RAM or T-EWE ewes (10.1+/-2.2 vs 9.8+/-2.3 vs 11.6+/-2.3 h, respectively). These
      results show that the expression and duration of estrus are not influenced by
      different types of mating stimuli in hair sheep ewes. In addition, the timing and
      the magnitude of LH release does not appear to be influenced by mating stimuli
      around the time of estrus.

PMID- 11291913
TI  - Effects of injection of hcg during the estrous cycle on follicle development and
      the inter-estrous interval.
AB  - Pseudopregnancy in pigs can be induced by the administration of a single dose of
      hCG at Day 12 of the estrous cycle. However, the resulting length of
      pseudopregnancy can be extremely variable. In this study, it was investigated
      whether time of hCG administration (day of the cycle) and degree of follicle
      growth after hCG administration were related to the length of inter-estrous
      interval (pseudopregnancy). In the first experiment, groups of cyclic gilts were
      given 1500 IU hCG at either Day 11 (D 11; n=14) or Day 12 (D12; n=14) after onset
      of estrus, or not treated (Control; n=13). Follicle development was assessed
      daily using transcutaneous ultrasonography. Follicle size in the Control gilts
      remained relatively constant between Days 11 and 17, whereas in the treated
      gilts, follicle size increased (P < 0.001) within 4 days (D11) and 2 days (D12)
      after treatment. The inter-estrous interval was increased (P < 0.01) in the hCG
      treated gilts (34.7+/-6.3 and 37.6+/-11.1 days in the D11 and D12 gilts,
      respectively), compared to Controls (22.3+/-5.2 d). About two-thirds of the
      treated gilts returned to estrus between Days 32 and 39 after onset of first
      estrus. No relationships were found between follicle development after treatment
      and length of the inter-estrous interval. In a second experiment, 16 cyclic gilts
      were treated with 1500 IU hCG at Day 12 and Day 15 of the estrous cycle. Follicle
      development was assessed at Days 12, 15 and 18. At Day 18, average follicle size
      was 8.4+/-2.0 mm. The inter-estrous interval was 39.7+/-5.4 days and 14 of 16
      gilts returned to estrus between Days 34 and 44 after onset of first estrus.
      Again, no relationships were found between follicle development after treatment
      and the duration of the inter-estrous interval. We conclude that, based on the
      duration of the inter-estrous interval, administration of hCG during the luteal
      phase induced a short pseudopregnancy. However, the induction of accessory
      corpora lutea or follicular luteinization cannot be discounted.

PMID- 11291912
TI  - Dynamics of meiosis and protein kinase activities in bovine oocytes correlated to
      prolactin treatment and follicle size.
AB  - Oocyte developmental competence depends on the size of the original follicle and
      is affected by compounds like prolactin. We wished to investigate nuclear and
      cytoplasmic maturation of bovine oocytes correlated to their origin and response
      to prolactin treatment, by monitoring at frequent intervals meiotic configuration
      of chromosomes and activity of histone H1 and MAP-kinase. Bovine ovaries were
      obtained from a slaughterhouse and oocytes were recovered by follicle isolation.
      Oocytes (n = 1,397) with a compact cumulus were selected from small (2 to 3 mm)
      and large (4 to 5 mm in diameter) follicles and cultured up to 28 h in TCM
      199+20% bull serum with or without 50 ng/mL bovine prolactin. Four groups of
      oocytes were formed: originating from small or large follicles, and treated or
      not treated with prolactin. At the scheduled time intervals for in vitro
      maturation, cumulus oocyte complexes from the 4 groups were randomly selected and
      the oocytes were analyzed for histone H1 and MAP-kinase, and for chromatin
      configuration. The first meiotic division took longer to complete in oocytes from
      large follicles (P < 0.01). Under the influence of prolactin the meiosis was
      prolonged in oocytes both from small and large follicles (P < 0.05). Histone H1
      and MAP-kinases started to be activated at approximately the same time, around 6
      h after beginning maturation. But after this time, significantly lower levels of
      both kinase activities were found in oocytes treated with prolactin, especially
      those treated during Meiosis I (P < 0.05). Our results indicate a correlation of
      chromatin configuration and histone H1/MAP-kinase activities.

PMID- 11291914
TI  - The influence of cumulus-oocyte complex morphology and meiotic inhibitors on the
      kinetics of nuclear maturation in cattle.
AB  - This study evaluated whether pre-established morphological classes of bovine
      cumulus oocyte complex (COCs) differ in their kinetics of meiosis resumption
      after 4 h of incubation and whether the timing of COCs resumption of meiosis
      differed after a period of maintained meiotic arrest. Bovine COCs were aspirated
      from 2- to 5- mm follicles and classified according to the state of their cumulus
      cells and cytoplasm (Classes 1 to 3). Groups of 15 to 20 COCs were fixed at 0 h
      or after an incubation period of 4 h. In addition, COCs from Class 1 were first
      incubated for 4 h on a theca cell monolayer or in the presence of 2 microg/mL of
      cycloheximide, rinsed and then incubated in cycloheximide and theca cell-free
      medium for another 4 h. Oocytes then were fixed and evaluated for state of
      nuclear maturation. Results show that at 0 h, COCs from Class 3 have fewer
      oocytes at the GV stage than COCs from Class 1 and Class 2 (respectively 69.3+/
      3.2 vs 88.8+/-3.4% and 86.9% GV+/-4.3% SEM; P < 0.05). After 4 h of incubation,
      all COCs classes show a significant decrease in the number of COCs at the GV
      stage. The COCs maintained in meiotic arrest and then incubated for 4 h resume
      meiosis faster than COCs incubated in cycloheximide and theca cell-free medium
      (19.4+/-2.5, 33.3+/-7.3 and 59.9+/-6.5% GV SEM, respectively). The COCs of Class
      3 have fewer oocytes at the GV stage at the beginning of incubation than all
      other classes. The number of COCs at the GV stage after 4 h of incubation in
      cycloheximide and theca cell-free medium is not significantly different than
      those COCs incubated in the presence of theca cell monolayers for 24 h (58.8+/
      6.5 vs. 56.4+/-6.4% SEM; respectively). Our results indicate that the ability of
      theca cells to maintain oocytes at the GV stage could be limited to those oocytes
      that were not committed or primed in vivo to resume maturation as indicated by
      their faster maturation kinetics.

PMID- 11291915
TI  - Delipidating in vitro-produced bovine zygotes: effect on further development and
      consequences for freezability.
AB  - To study the effect of partial removal of intracytoplasmatic lipids from bovine
      zygotes on their in vitro and in vivo survival, presumptive zygotes were
      delipidated by micromanipulation and cocultured with Vero cells in B2+10% FCS.
      Blastocyst rates of delipidated (n=960), sham (centrifuged but not delipidated,
      n=830) and control embryos (n=950) were 42.1, 42.3 and 39.9% respectively (P >
      0.05). Day 7 blastocysts derived from delipidated zygotes had a mean of 123.9 +/
      45.6 nuclei compared to 137.5+/-32.9 for control blastocysts (P > 0.05). The full
      term development of delipidated blastocysts after single transfer to recipients
      was similar to that of control IVF blastocysts (41.2% vs 45.4% respectively). To
      assess the effect of delipidation on the embryo tolerance to freezing/thawing,
      delipidated (n=73), control (n=67) and sham (n=50) Day 7 blastocysts were frozen
      in 1.36 M glycerol + 0.25 M sucrose in PBS. After thawing, embryos were
      cocultured for 72 h with Vero cells in B2+10% FCS. Survival rates at 24 h were
      not significantly different between groups. However, in the delipidated group,
      the survival rate after 48 h in culture was significantly higher than in the
      control group (56.2 vs 39.8, P < 0.02), resulting in a higher hatching rate after
      3 days in culture (45.2 vs 22.4, P < 0.02). Pregnancy rates for delipidated and
      control frozen/thawed embryos were respectively 10.5 and 22.2% (P > 0.05).
      Electron microscopic observations showed much fewer lipid droplets (and smaller)
      in delipated blastocysts than in controls. Taken together, our data show that
      delipidation of one cell stage bovine embryos is compatible with their normal
      development to term and has a beneficial effect on their tolerance to freezing
      and thawing at the blastocyst stage. This procedure, however, alters the
      developmental potential of such blastocysts, suggesting that maternally inherited
      lipid stores interfere with metabolic recovery after thawing.

PMID- 11291916
TI  - Effect of dominant follicle removal before superstimulation on follicular growth,
      ovulation and embryo production in Holstein cows.
AB  - This study was to investigate whether removing the dominant follicle 48 h before
      superstimulation influences follicular growth, ovulation and embryo production in
      Holstein cows. After synchronization, ovaries were scanned to assess the presence
      of a dominant follicle by ultrasonography with a real-time linear scanning
      ultrasound system on Days 4, 6 and 8 of the estrus cycle (Day 0 = day of estrus).
      Twenty-six Holstein cows with a dominant follicle were divided into 2 groups in
      which the dominant follicle was either removed (DFR group, n=13) by ultrasound
      guided follicular aspiration or left intact (control group, n=13) on Day 8 of the
      estrus cycle. Superovulation treatment was initiated on Day 10. All donors were
      superovulated with injections of porcine FSH (Folltropin) twice daily with
      constant doses (total: 400 mg) over 4 d. On the 6th and 7th injections of
      Folltropin, 30 mg and 15 mg of PGF2alpha (Lutalyse) were given. Donors were
      inseminated twice at 12 h and 24 h after the onset of estrus. Embryos were
      recovered on Day 6 or 7 after AI. During superstimulation, the number of
      follicles 2 to 5 mm (small), 6 to 9 mm (medium) and > or = 10 mm (large) was
      determined by ultrasonography on a daily basis. At embryo recovery, the number of
      corpora lutea (CL) was also determined by ultrasonography and blood samples were
      collected for analysis of progesterone concentration. Follicular growth during
      superstimulation was earlier in the DFR group than in the control group. The
      number of medium and large follicles was greater (P < 0.01) in the DFR group than
      in the control group on Days 1 to 2 and Days 3 to 4 of superstimulation,
      respectively. The numbers of CL (9.6+/-1.1 vs 6.1+/-0.9) and progesterone
      concentration (30.9+/-5.4 vs 18.6+/-3.5 ng/mL) were greater (P < 0.05) in the DFR
      group than in the control group, respectively. The numbers of total ova (7.7+/
      1.3 vs 3.9+/-1.0) and transferable embryos (4.6+/-0.9 vs 2.3+/-0.8) were also
      greater (P < 0.05) in the DFR group than in the control group, respectively. It
      is concluded that the removal of the dominant follicle 48 h before
      superstimulation promoted follicular growth, and increased ovulation and embryo
      production in Holstein cows.

PMID- 11291917
TI  - Assessment of sperm quality through fluorometry and sperm chromatin structure
      assay in relation to field fertility of frozen-thawed semen from Swedish AI
      bulls.
AB  - We investigated fluorometry to study sperm viability and flow cytometry to study
      sperm chromatin structure. We also assessed sperm quality after thawing relative
      to field fertility after AI as shown by 56-day non-return rates (56-d NRR) Frozen
      thawed semen samples were obtained from 20 Swedish Red and White bulls (1 to 3
      semen batches/bull) and the fertility data were based on 6,369 AIs. Fluorometry
      enabled simultaneous detection of sperm viability and concentration in Hoechst
      33258-stained semen samples. Sperm chromatin structure assay (SCSA) evaluated
      denaturability of sperm nuclear DNA in situ after acid treatment. The intensity
      of fluorescence in non-permeabilized samples was negatively (r = -0.60, P <
      0.001) correlated with microscopically-assessed sperm viability, and the
      fluorescence of permeabilized semen samples significantly (r = 0.67, P < 0.001)
      correlated with sperm concentration as assessed by hemocytometry. From the
      fluorescence output, the calculated percentage of damaged cells was negatively (r
      = -0.71, P < 0.001) correlated with the number of live cells derived from the
      microscopic assessment of sperm viability and concentration. This variable was
      significantly correlated with fertility results both at batch (r = -0.39, P <
      0.05), and bull (r = -0.57, P < 0.01) levels. The SCSA variables SDalphat and
      COMPalphat were significantly (r = -0.59-0.64, P < 0.001) correlated with sperm
      viability variables after thawing but only the COMPalphat correlated
      significantly (r = -0.53, P < 0.05) with fertility results and solely at the bull
      level. The results indicate that fluorometric assessment is in good agreement
      with other practiced procedures and can be performed with sufficient accuracy.
      The SCSA may be a valuable complement for routinely practiced microscopic
      evaluation of sperm morphology of AI bull semen

PMID- 11291918
TI  - Development of the Canadian beef reference herd for gene mapping studies.
AB  - A project to map quantitative trait loci (QTL), in beef cattle using a full-sib
      design was initiated using six Bos taurus breeds. Embryo transfer was used in a
      large scale, short timeframe experiment to develop this herd for gene mapping.
      Full-sib families allowed for genetic information to be followed through both the
      sire and the dam and for both parents to be slaughtered so that carcass quality
      data could also be obtained from both of them at close to typical slaughter ages.
      Repeatability of response to superovulation was significant among the 3 flushes
      per female. Response to superovulation was negatively correlated with backfat of
      the donor. Crossbred embryos were found to have higher survival than purebred
      embryos.

PMID- 11291919
TI  - Effects of immunization against GnRH, melengestrol acetate, and a trenbolene
      acetate/estradiol implant on growth and carcass characteristics of beef heifers.
AB  - A 2 x 3 factorial experiment was conducted to determine the effects of an implant
      (trenbolene acetate/estradiol or no implant) and method of estrus suppression
      (immunization against GnRH, melengestrol acetate, or no suppression) on growth
      performance and carcass characteristics of heifers fed for slaughter. At the
      start of a 21-d feed adaption phase, crossbred beef heifers (n = 144, 390+/-2.8
      kg) were given their first dose of an anti-GnRH vaccine or started on
      melengestrol acetate (MGA). Thereafter, heifers were fed a high-concentrate diet
      (78% barley grain) for 84 d (Days 0 to 83), received implants on Day 0, a second
      vaccination on Day 21, and were slaughtered on Days 84 or 85. Implanting
      increased average daily gain (1.72 vs 1.50 kg/d, P < 0.01), feed efficiency (6.02
      vs 6.75 kg dry matter intake/kg gain, P < 0.01), preslaughter weight (532 vs 513
      kg, P < 0.01), carcass weight (301 vs 289 kg, P < 0.01), and ribeye area (88.6 vs
      85.9 cm2, P < 0.05), but had no affect (P > 0.05) on dry matter intake, grade fat
      thickness, marbling score, or lean yield. Compared to heifers fed MGA, those
      immunized against GnRH had a greater ribeye area (90.0 vs 84.6 cm2) and lean
      yield (63 vs 61%), and had thinner grade fat (7.5 vs 8.6 mm; P < 0.05 for each).
      Furthermore, immunized heifers had lower (P < 0.001) plasma progesterone
      concentrations than control heifers on Days 42, 63 and 83. Heifers fed MGA had
      less estrus mounting activity (P < 0.05) and lower plasma progesterone
      concentrations (P < 0.001) than the remaining heifers. Method of estrus
      suppression did not affect (P > 0.05) preslaughter weight, average daily gain,
      dry matter intake, feed efficiency, carcass weight, or marbling score. In
      conclusion, implanting significantly increased growth performance and
      preslaughter and carcass weights. Compared to heifers fed MGA, immunization
      against GnRH significantly increased ribeye area and lean yield, and reduced
      grade fat thickness

PMID- 11291920
TI  - Testicular concentration of meiosis-activating sterol is associated with normal
      testicular descent.
AB  - In the cryptorchid stallion, spermatogenesis is arrested at various levels before
      the completion of meiosis. In men, infantile cryptorchidism is also often
      associated with oligo- and azoospermia during adulthood. An impairment of
      spermatogenesis might be reflected in the level of locally produced factors.
      Formerly, a meiosis-activating sterol (T-MAS) has been isolated in murine and
      bovine testes. This sterol possesses the potential to trigger resumption of
      meiosis in cultured mouse oocytes, indicating that it might play an important
      role in the regulation of the meiotic process in the female gamete. The function
      of T-MAS in the testis is still unclear, but T-MAS may be associated with
      spermatogenesis. The objectives of this study were 1) to demonstrate the presence
      of T-MAS in equine testes, 2) to compare the contents of T-MAS in testicular
      tissue of stallions with complete and incomplete testicular descent and 3) to
      compare testicular T-MAS concentration before and after puberty Testes were
      collected from 16 normal and cryptorchid stallions submitted for castration and
      stored at -80 degrees C until the content of T-MAS was measured quantitatively
      with an HPLC-assay. In stallions > or = 2 years of age, the content of T-MAS was
      higher (P < 0.001) in normal testes (19.3+/-1.1 microg T-MAS/g, n=7) than in
      inguinally (4.1+/-2.4 microg T-MAS/g, n=4) or abdominally located testes (1.6+/
      0.2 microg T-MAS/g, n=2). The contents of T-MAS in normal testes from stallions <
      2 years of age (2.8+/-1.5 microg T-MAS/g, n=4) was lower than in normal testes
      from stallions > or =2 years of age (P < 0.001) From the present study it can be
      concluded that T-MAS is present in equine testicular tissue. Furthermore, the
      present study demonstrates that the production of T-MAS in testicular tissue is,
      concurrently with spermatogenesis, associated with normal testicular descent and
      is temporarily related to the onset of puberty.

PMID- 11291921
TI  - Effect of long-term and short-term progestagen treatment on follicular
      development and pregnancy rate in cyclic ewes.
AB  - The aim of this study was to evaluate the effect of the length of a progestagen
      treatment (12 d vs. 6 d) on follicular dynamics, estrus synchronization and
      pregnancy rate using medroxyprogesterone acetate (MAP) with or without an eCG
      dose at the end of MAP treatment. One hundred sixty Polwarth ewes were divided
      into four equal groups: long-term treated (LT, n=40); short-term treated (ST,
      n=40); long-term treated plus eCG (LTeCG, n=40); and short-term treated plus eCG
      (STeCG, n=40). Five ewes of each group were separated to undergo daily
      transrectal ultrasonography, and blood samples were taken for hormone
      determination. Until 96 h after sponge withdrawal the number of ewes in estrus
      was higher in both long-term-treated groups than in both short-term-treated
      groups but at the end of the observational period (144 h) no significant
      differences were found among groups. The pregnancy rate was higher in the ST
      group (87%) than in the other groups (LT, 63%; LTeCG, 67%; and STeCG, 58%; P< or
      =0.03). The ovulatory follicle emerged before sponge withdrawal in long-term
      treated ewes (-3.8+/-0.4 d and -2.2+/-0.8 d for LT and LTeCG, respectively),
      whereas in short-term-treated ewes it emerges around sponge removal (0.4+/-1.1 d
      and 0.5+/-0.5 d for ST and STeCG, respectively; P< or =0.01). The ovulatory
      follicle in the LT group had a longer lifespan and attained a larger (P< or
      =0.05) maximum diameter than in the ST group. We conclude: a) that the lower
      pregnancy rate observed after long-term progestagen treatment was related to a
      slower follicular turnover that promoted the ovulation of persistent dominant
      follicles; (b) that short-term treatment resulted in a higher pregnancy rate
      probably due to the ovulation of newly recruited growing follicles; and (c)
      treatment with eCG had no advantage in association with long-term treatment and
      had a deleterious effect in combination with short-term treatment with MAP.

PMID- 11291922
TI  - Controversies in clinical pancreatology. The management of severe gallstone
      pancreatitis.

PMID- 11291923
TI  - Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma
      of the pancreas.
AB  - The Bcl-2 family of genes plays important roles in the regulation of apoptosis.
      The present study was designed to assess the clinicopathologic significance of
      apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2)
      and the apoptosis-promoting Bax protein (pBax) in human invasive ductal
      carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were
      resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end
      labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis
      was quantified as the apoptotic index (AI, the percentage of apoptotic cells of
      the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%)
      IDCs. The AI correlated significantly with the extent of nodal involvement. pBax
      immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was
      significantly correlated with female gender and showed a significant negative
      correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs
      (24%) but did not show any correlation with the clinicopathologic factors. The AI
      did not correlate with the expression of pBcl-2 or pBax, but there was a
      significant correlation between the expression of pBcl-2 and that of pBax; 15 of
      the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-).
      Univariate analysis demonstrated that the degree of apoptosis had no significant
      influence on the patients' prognosis, pBax or pBcl-2 expression was significantly
      associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group
      had a significantly higher survival than the other groups. On the other hand, the
      survival curve of the adjuvant chemotherapy (ACT) group was also higher than that
      of the surgery alone (SA) group, with borderline statistical signfiicance. The
      ACT group showed a significantly better survival rate than the SA group for the
      pBax(+)IDC patients, but the AI and pBcl-2 expression were not correlated with an
      improved survival rate in the ACT group. Multivariate analysis showed that the
      AI. pBcl-2 expression, and pBax expression by themselves did not represent
      significant variables for death owing to IDC, but pBax expression was
      significantly associated with the efficacy of ACT. In conclusion, pBax expression
      may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not
      significant prognostic factors for patients with IDC, but pBax expression may be
      beneficial in predicting the effects of ACT on patients with IDC.

PMID- 11291924
TI  - Pattern of distribution and prognostic value of angiogenesis in pancreatic duct
      carcinoma: a semiquantitative immunohistochemical study of 45 patients.
AB  - In specimens obtained from resected pancreata, the intratumoral microvessel
      density (IMD), the proliferation rate of the neoplastic parenchymal cells, and
      their p53 protein expression were assessed. The sources of errors were great in
      the measurements of the IMD. This statement can be illustrated by the finding
      that when the IMD was calculated by manual counting in five areas of intense
      neovascularization (hot spot regions), using x200 and x400 magnifications, the
      numbers of microvessels per square millimeter were 65+/-23 and 106+/-8,
      respectively, which reflects a significant difference. Two patterns of
      microvessel distribution could be identified: one with hot spots only in the
      stroma (n = 19) and one in which the hot spots were located in areas of
      neoplastic parenchyma (including its stroma) (n = 26). The IMD was significantly
      greater in the latter group. There was no general correlation of neoplastic
      disease with the IMD. However, when a scoring system was used to assess the
      angiogenesis, hot spots in areas of neoplastic parenchyma were associated with a
      greater proliferation rate of the tumor cells, and with a short length of
      survival of the patients from their neoplastic disease.

PMID- 11291925
TI  - Endothelin mediates local and systemic disease sequelae in severe experimental
      pancreatitis.
AB  - Endothelin-1 has been shown to reduce pancreatic blood flow and cause focal
      acinar cell necrosis similar to those seen in acute pancreatitis (AP), whereas
      therapy with endothelin receptor antagonists enhanced pancreatic capillary blood
      flow (PCBF) and decreased mortality rates. The current study evaluated the role
      of endothelin in the development of severe AP. Trypsinogen activation peptides,
      acinar cell necrosis, and PCBF were used as local indicators of disease severity,
      fluid sequestration, cardiorespiratory and renal parameters, and colonic
      capillary blood flow as systemic disease indicators. The following groups of
      animals were examined: 1) rats with mild edematous AP and 2) severe necrotizing
      AP treated with and without endothelin, 3) transgenic rats overexpressing
      endothelin with severe AP, and 4) rats with severe AP prophylactically treated
      with endothelin receptor antagonists. The following observations were made:
      endothelin superimposed on mild AP caused hemoconcentration, a decrease in PCBF,
      and necrosis and ascites not seen in this model without endothelin exposure.
      Endothelin superimposed on severe AP had no significant effects. After induction
      of severe AP, less PCBF and more acinar cell necrosis were observed in transgenic
      rats than in their normal littermates. Prophylactic endothelin receptor
      antagonists improved local (acinar necrosis, PCBF) and systemic parameters
      (ascites, urine production, colonic capillary blood flow) of disease severity in
      animals with severe AP. These observations underscore the role of endothelin as a
      mediator of disease severity in AP and suggest that endothelin receptor blockade
      may become a promising therapeutic tool in this disease.

PMID- 11291927
TI  - Oxidative stress in blood of patients with alcohol-related pancreatitis.
AB  - To determine the possible role of oxidative stress in alcoholic pancreatitis, the
      authors measured the ability of blood neutrophils of 22 patients with acute and
      20 patients with chronic alcoholic pancreatitis to produce superoxide anion (O2-)
      and hydrogen peroxide (H2O2), spontaneously and after in vitro stimulation with
      phorbol ester and compared it with that of neutrophils isolated from the blood of
      16 healthy controls. In addition, they measured serum activities of superoxide
      dismutase, catalase, and the serum concentration of glutathione peroxidase (GPx).
      Phorbol ester-induced O2- and H2O2 production in neutrophils of patients with
      acute and chronic pancreatitis was greater than in controls, but these
      differences, except of superoxide anion production by neutrophils of patients
      with chronic pancreatitis, were not statistically significant because of large
      individual differences. Spontaneous resting production of O2- and H2O2 by
      neutrophils of patients with chronic pancreatitis was significantly greater than
      in the controls. Superoxide dismutase and catalase activity was greater in sera
      of both groups of patients with acute and chronic alcoholic pancreatitis than in
      controls, but GPx concentration was significantly less in the sera of patients
      with chronic pancreatitis. Impaired GPx production and increased production of O2
      and H2O2 by neutrophils may result in increased lipid peroxidation and could
      play a role in the pathogenesis of chronic alcoholic pancreatitis.

PMID- 11291926
TI  - Caspase-3 activation downstream from reactive oxygen species in heat-induced
      apoptosis of pancreatic carcinoma cells carrying a mutant p53 gene.
AB  - In the present study we investigated the intracellular signaling pathway leading
      to p53-independent activation of caspase-3 during heat-induced apoptosis of
      pancreatic carcinoma cells. Induction of mutant p53 protein, but not p21/WAF-1,
      was observed after heat treatment of both heat-resistant (PANC-1) and heat
      sensitive (MIAPaCa-2) cells. A specific inhibitor of caspase-3 (Ac-DMQD-CHO)
      caused 84% and 92% inhibition of apoptosis in MIAPaCa-2 and PANC-1 cells,
      respectively. Caspase-3 mRNA expression was increased in both cell lines after
      heat treatment. Further, heat-induced caspase-3 activity detected by fluorogenic
      assay in MIAPaCa-2 cells was almost completely inhibited by addition of the
      antioxidant N-acetyl-L-cysteine. In contrast, Ac-DMQD-CHO had no inhibitory
      effect on amounts of reactive oxygen species in heat-treated MIAPaCa-2 cells.
      These results suggest a possible pathway by which reactive oxygen species lead to
      caspase-3 activation to cause heat-induced death of pancreatic carcinoma cells
      carrying mutant p53.

PMID- 11291928
TI  - Congenital arteriovenous malformation of the pancreas: its diagnostic features on
      images.
AB  - To analyze diagnostic features on images of congenital arteriovenous malformation
      (AVM) of the pancreas, we analyzed the diagnostic findings in six patients with
      the disease, using gray-scale ultrasonography (US), color Doppler US, computed
      tomography, and angiography and analyzed previously reported cases. AVM
      characteristic findings on images were multiple, small hypoechoic nodules on US,
      mosaic appearance of the lesion and pulsatile wave form in the portal vein on
      color Doppler US, conglomerated small nodular enhancement of the lesion and early
      appearance of the portal vein on CT, and a racemose network and early appearance
      of the portal vein on angiography. Five of the six patients underwent surgery,
      and all resected specimens were histologically found to be AVMs of the pancreas;
      however, one with developed portal hypertension at surgery died of repeated
      bleeding from esophageal varices. From analysis of total of 35 cases including
      our six cases, a mosaic appearance of the lesion was found in 100% and a
      pulsatile wave form in the portal vein in 77.8% on color Doppler US. Color
      Doppler US is noninvasive and useful for detecting congenital AVM of the pancreas
      at an early stage, preventing the portal hypertension causing esophageal varices
      and their rupture.

PMID- 11291929
TI  - Early severe acute pancreatitis: characteristics of a new subgroup.
AB  - This study focuses on patients with severe acute pancreatitis complicated by
      organ failure within the initial phase of the disease. Data of 158 patients with
      severe acute pancreatitis (SAP) admitted to hospital within 72 hours after onset
      of symptoms were prospectively documented and analyzed for the occurrence of
      early severe acute pancreatitis (ESAP). ESAP was defined as presence of organ
      failure (OF) at admission. Forty-seven (30%) patients had ESAP, compared with 111
      patients without OF (SAP group). In a multivariate analysis, the main factor
      predisposing to ESAP was the presence of extended pancreatic necrosis (odds
      ratio, 3.8), whereas biliary pancreatitis was associated with a slightly lower
      risk compared with alcoholic pancreatitis (odds ratio, 0.34). Compared with SAP,
      patients with ESAP more frequently developed intractable organ failure, which
      posed the indication for surgical treatment. Surgical necrosectomy due to
      progressive OF had to be performed in 89% of the ESAP patients and in 60% of the
      SAP patients. The incidence of infected pancreatic necrosis did not differ
      between both groups (23 vs. 21%). Mortality was significantly higher in ESAP (42
      vs. 14%; p = 0.0003). ESAP is characterized by the presence of extended
      pancreatic necrosis and a complicated clinical course. Intractable organ failure
      is a frequent finding. Given the poor prognosis of ESAP, these patients should be
      treated in specialized intensive care units.

PMID- 11291930
TI  - Abdominal pain in patients with resectable pancreatic cancer with reference to
      clinicopathologic findings.
AB  - Abdominal and/or back pain is one of the most common symptoms in patients with
      pancreatic cancer. However, the cause of the pain and the clinicopathologic
      features of patients with pain have not been fully elucidated. We retrospectively
      determined the factors related to preoperative abdominal and/or back pain in 95
      patients with resectable pancreatic cancer. Pancreatic tumor size, invasion of
      the intrapancreatic nerves, invasion of the anterior pancreatic capsule, and
      lymph node metastasis were determined to be variables related to the pain.
      Pancreatic tumor size, invasion of anterior pancreatic capsule, and lymph node
      metastasis were also variables significantly correlating to pain intensity.
      Survival also correlated with pain intensity: the median survival periods were 29
      months in patients without pain, 19 months in those with mild pain, and 9 months
      in those with severe pain who required analgesics. Larger pancreatic tumors,
      invasion of the intrapancreatic nerves, and invasion of the anterior pancreatic
      capsule may cause abdominal and/or back pain in patients with resectable
      pancreatic cancer. This study also suggests clinical implications of the pain
      intensity as a prognostic factor in patients with resectable pancreatic cancer.

PMID- 11291931
TI  - Overexpression of lymphangiogenic growth factor VEGF-C in human pancreatic
      cancer.
AB  - Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide
      that has been implicated in cancer growth. In this study, we characterized VEGF-C
      expression in cultured human pancreatic cancer cell lines and determined whether
      the presence of VEGF-C in human pancreatic cancers is associated with
      clinicopathologic characteristics. VEGF-C mRNA transcripts were present in all
      five tested cell lines (Capan-1, MIA-PaCa-2, PANC-1, COLO-357, and T3M4).
      Immunoblotting with a highly specific anti-VEGF-C antibody revealed the presence
      of VEGF-C protein in all the cell lines. Northern blot analysis of total RNA
      revealed an approximately 2.2-fold increase in VEGF-C mRNA transcript in the
      cancer samples compared with the normal pancreas. Immunohistochemical analysis
      confirmed the expression of VEGF-C and its receptor flt-4 in the cancer cells
      within the tumor mass. Immunohistochemical analysis of 51 pancreatic cancer
      tissues revealed the presence of strong VEGF-C immunoreactivity in the cancer
      cells in 80.4% of the cancer tissues. The presence of VEGF-C in these cells was
      associated with increased lymphatic vessels invasion and lymph node metastasis,
      but not with decreased patient survival. These findings indicate that VEGF-C and
      its receptor are commonly overexpressed in human pancreatic cancers and that this
      factor may contribute to the lymphangiogenic process and metastasis in this
      disorder.

PMID- 11291932
TI  - Receptors and ligands for autocrine growth pathways are up-regulated when
      pancreatic cancer cells are adapted to serum-free culture.
AB  - Overexpression of autocrine growth factors and their receptors has been reported
      in many human cancers. The study of autocrine-regulated pathways using in vitro
      culture systems can be hindered by the presence of fetal bovine serum in culture
      medium. A human pancreatic cancer cell line (HPAF) was slowly weaned from its
      dependence on fetal bovine serum and subsequently maintained in serum-free
      conditions. Growth factor secretion studies showed that production of autocrine
      growth factors such as transforming growth factor alpha, gastrin-releasing
      peptide, and insulin-like growth factor I from weaned cells increased three times
      compared with nonweaned cells (p < 0.01). The epidermal growth factor and gastrin
      releasing peptide receptor densities were also increased in weaned cells (2 times
      and 2.5 times, respectively, p < 0.05). The proliferation of weaned cells
      cultured continuously in the same medium was significantly greater than of
      nonweaned cells (p < 0.05). Collectively, these data indicate that weaned
      pancreatic cancer cells can proliferate in the absence of serum by up-regulating
      autocrine pathways.

PMID- 11291933
TI  - Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and
      selenium in chronic pancreatitis.
AB  - Diabetes mellitus, a common complication of chronic pancreatitis, can disturb the
      metabolism of zinc, copper, and selenium. We analyzed the effects of
      hyperglycemia, malabsorption, and dietary intake on these factors in 35 men with
      alcohol-induced chronic pancreatitis complicated by insulin-treated diabetes
      mellitus (CP-D), 12 men with chronic pancreatitis but no diabetes (nondiabetic
      CP), 25 men with type 1 diabetes mellitus (type 1 DM), and 20 control subjects.
      Diabetes due to chronic pancreatitis was associated with decreased plasma zinc
      and selenium concentrations and with increased urinary copper excretion. Of the
      chronic pancreatitis patients, 17% had low plasma zinc, and 41% of them had low
      plasma selenium. None of the type 1 diabetic patients had low plasma
      concentrations of zinc, but 12% of them had a low selenium concentration.
      Hyperglycemia, as assessed by fasting plasma glucose and by plasma HbAlc, was
      responsible for the increased zinc excretion and the decreased superoxide
      dismutase activity. The perturbations of the copper, selenium, and zinc
      metabolism were particularly pronounced in subjects with chronic pancreatitis
      plus diabetes mellitus. We have yet to determine whether the differences in trace
      element status contribute to the clinical expression of the disease.

PMID- 11291934
TI  - High glucose concentration favors the selective secretion of islet amyloid
      polypeptide through a constitutive secretory pathway in human pancreatic islets.
AB  - We studied the contribution of the constitutive and the regulated pathways to the
      total secretion of islet amyloid polypeptide (IAPP) in human pancreatic islets
      after prolonged culture at either 5.5 or 24.4 mM glucose. In islets cultured in
      low concentrations of glucose, the secretion of IAPP in response to glucose was
      unaffected by brefeldin A (BFA) and completely blocked by
      ethyleneglycoltetraacetic acid. In islets cultured in high glucose
      concentrations, it was strongly inhibited by both agents. BFA had no effect on
      the glucose-induced insulin secretion. The determination of the islet peptide
      contents and the mRNA levels revealed a several-fold increase in the IAPP/insulin
      molar ratio of islets cultured in high glucose concentrations. Thus, prolonged
      exposure of human islets to high concentrations of glucose results in an increase
      in the synthesis of IAPP with respect to insulin. As a result, the release of
      IAPP through a mechanism sensitive to BFA is favored. These data support the
      hypothesis that IAPP and insulin are regulated in a noncoordinated way in human
      pancreatic islets.

PMID- 11291935
TI  - Streptozotocin-Induced diabetes mellitus is associated with increased pancreatic
      tissue levels of noradrenaline and adrenaline in the rat.
AB  - The pancreata of streptozotocin-induced diabetic rats were examined to determine
      whether the pancreatic tissue content of catecholamines is altered after the
      onset of diabetes. Experimental diabetes was induced by intraperitoneal injection
      of streptozotocin (60 mg/kg body weight). Four weeks after the induction of
      diabetes, pancreatic tissue fragments were taken from the tail end of the
      pancreas and processed for catecholamine content using the high-performance
      liquid chromatography method. Immunohistochemical analysis showed that the
      pancreata of diabetic rats contained more tyrosine hydroxylase-positive nerves
      compared with controls. Pancreatic noradrenaline content, expressed as the mean
      +/- SD, was significantly (p < 0.03) greater in diabetic rats (54+/-11.74 pg x
      mL(-1) x mg tissue(-1)) compared with normal, sex- and age-matched control rats
      (37.54+/-1.18 pg x mL(-1) x mg tissue(-1)). Similarly, the adrenaline content in
      diabetic rat pancreatic tissue (102.69+/-20.24 pg x mL(-1) mg tissue(-1)) was
      markedly greater (p < 0.003) compared with sex- and age-matched controls (35+/
      9.23 pg x mL(-1) x mg tissue(-1)). In contrast, 5-hydroxyindole acetic acid
      decreased significantly (p < 0.0002) in diabetic pancreatic tissue (13.41+/-0.87
      pg x mL(-1) x mg tissue(-1)) compared with controls (80.72+/-1.46 pg x mL(-1) x
      mg tissue(-1)). The plasma levels of these catecholamines also increased slightly
      but not significantly in diabetic rats compared with controls. These results
      suggest that diabetes is associated with increased noradrenaline and adrenaline
      and decreased 5-hydroxyindole acetic acid pancreatic tissue levels. These
      disturbances in catecholamine metabolism may play a role in the pathogenesis of
      the acute and chronic complications of diabetes mellitus.

PMID- 11291936
TI  - Effects of synthetic serine protease inhibitors on proliferation and collagen
      synthesis of human pancreatic periacinar fibroblast-like cells.
AB  - Protease inhibitors are currently used as therapeutic agents for chronic
      pancreatitis in Japan. We previously reported that human pancreatic periacinar
      fibroblast-like cells (hPFCs) could be cultured from isolated pancreatic acini,
      and those are thought to play a crucial role in pancreatic fibrosis correlating
      with platelet-derived growth factor (PDGF) and transforming growth factor beta1
      (TGF-beta1) (Pancreas 1997;14: 373-82). The present study was designed to examine
      the effects of synthetic serine protease inhibitors (FOY-007 and FOY-305) on
      proliferation and collagen synthesis of hPFCs under cytokine stimulation. The
      cell proliferation and collagen synthesis were evaluated using assays of [3H]
      thymidine incorporation and procollagen type I c-terminal peptide (PIP), and
      [14C]-proline incorporation to de novo synthesized collagen, respectively. The
      cell proliferation stimulated by PDGF was inhibited by the application of FOY-007
      dose dependently (1-100 microM) and FOY-305 at 100 microM. FOY-007 attenuated the
      collagen synthesis and PIP production stimulated by TGF-beta1 dose dependently,
      but FOY-305 inhibited only PIP production. Both protease inhibitors demonstrated
      no effect on the proliferation and collagen synthesis of hPFCs when they were not
      stimulated by PDGF or TGF-beta1. Thus, serine protease inhibitors act on hPFCs to
      diminish the effects of PDGF on proliferation and the effects of TGF-beta1 on
      collagen synthesis.

PMID- 11291938
TI  - Artificial intelligence and meaning--some philosophical aspects of decision
      making.

PMID- 11291937
TI  - Concurrent chemoradiation is effective in the treatment of alpha-fetoprotein
      producing acinar cell carcinoma of the pancreas: report of a case.

PMID- 11291939
TI  - Forecasting physicochemical variables by a classification tree method.
      Application to the Berre Lagoon (south France).
AB  - The dynamics of the "Etang de Berre", a brackish lagoon situated close to the
      French Mediterranean sea coast, is strongly disturbed by freshwater inputs coming
      from an hydroelectric power station. The system dynamics has been described as a
      sequence of daily typical states from a set of physicochemical variables such as
      temperature, salinity and dissolved oxygen rates collected over three years by an
      automatic sampling station. Each daily pattern summarizes the evolution, hour by
      hour of the physicochemical variables. This article presents results of forecasts
      of the states of the system subjected to the simultaneous effects of
      meteorological conditions and freshwater releases. We recall the main step of the
      classification tree method used to build up the predictive model (Classification
      and Regression Trees, Breiman et al., 1984) and we propose a transfer procedure
      in order to test the stability of the model. Results obtained on the Etang de
      Berre data set allow us to describe and predict the effects of the environmental
      variables on the system dynamics with a margin of error. The transfer procedure
      applied after the tree building process gives a maximum gain in prediction
      accuracy of about 15%.

PMID- 11291940
TI  - Software sensors to monitor the dynamics of microbial communities: application to
      anaerobic digestion.
AB  - A mass balance based model has been derived to represent the dynamical behavior
      of the ecosystem contained in an anaerobic digester. The model considers two
      bacterial populations: acidogenic and methanogenic bacteria. It forms the basis
      for the design of a software sensor considering both a model of the biological
      system and on-line gaseous measurements. The software sensor computes the
      concentration of inorganic carbon and volatile fatty acids (VFA) in the digester.
      Another software sensor is dedicated to the estimation of the bacterial
      biomasses. The predictions of the software sensors for a real experiment are very
      close to the actual off-line measurements. The software sensors monitor the
      accumulation of VFA and thus very early detect a destabilization of the digester
      due to overloading. The presented methodology demonstrates the usefulness of
      advanced monitoring techniques for an improved understanding of the internal
      working of a biological system.

PMID- 11291941
TI  - The dynamics of a fish stock exploited in two fishing zones.
AB  - This work presents a specific stock-effort dynamical model. The stocks correspond
      to two populations of fish moving and growing between two fishery zones. They are
      harvested by two different fleets. The effort represents the number of fishing
      boats of the two fleets that operate in the two fishing zones. The bioeconomical
      model is a set of four ODE's governing the fishing efforts and the stocks in the
      two fishing areas. Furthermore, the migration of the fish between the two patches
      is assumed to be faster than the growth of the harvested stock. The displacement
      of the fleets is also faster than the variation in the number of fishing boats
      resulting from the investment of the fishing income. So, there are two time
      scales: a fast one corresponding to the migration between the two patches, and a
      slow time scale corresponding to growth. We use aggregation methods that allow us
      to reduce the dimension of the model and to obtain an aggregated model for the
      total fishing effort and fish stock of the two fishing zones. The mathematical
      analysis of the model is shown. Under some conditions, we obtain a stable
      equilibrium, which is a desired situation, as it leads to a sustainable
      harvesting equilibrium, keeping the stock at exploitable densities.

PMID- 11291942
TI  - Combinatorial properties of some cellular automata related to the mosaic cycle
      concept.
AB  - A cellular automaton that is related to the "mosaic cycle concept" is considered.
      We explain why such automata sustain very often, but not always, n-periodic
      trajectories (n being the number of states of the automaton). Our work is a first
      step in the direction of a theory of these type of automata which might be useful
      in modeling mosaic successions.

PMID- 11291943
TI  - Does help in decision-making in biology help in decision-making in human sciences
      and conversely?
AB  - A link between biological and human sciences may be established, under the
      condition that we should admit the existence of reciprocal influences between
      them. The model for the regulation of agonistic antagonistic couples (MRAAC) is
      built from the study of biological systems and gives rise to specific types of
      control. This model can be helpful in decision processes in some human sciences
      such as management, economical and political strategies. The reason for such an
      opportunity lies in the fact that MRAAC is a general and phenomenological model
      able to incorporate the whole of the agonistic antagonistic systems. This type of
      regulation might be related to the concept of the viability of a system (yet also
      valid for human science systems) and to a functional and structural pattern which
      is the basis for agonistic antagonistic networks.

PMID- 11291944
TI  - Hydrodynamic model of heat stroke.
AB  - This work presents an hydrodynamical model of heat stroke, which is a
      physiopathological state of stress, due to an exposure of animals to an ambient
      temperature of approximatively 40 degrees C during two hours. The evolution of
      body temperature during this stress process is characterised by three phases. A
      first phase of increase is followed by a plateau which occurs before a second
      phase of increase which can be lethal. The model is based on the analogy of a
      boat progressively caught in a whirlpool. The evolution of the degree of freedom
      lost by the boat is mathematically analysed and this study leads to the same
      three phases. The theoretical curves calculated during this study are well in
      agreement with the experimental curves obtained with animals. This analogy is
      compared to a previous one which has been made during another experiment with
      animals constrained by chemical intoxications. It seems that stress can be
      considered as a vital vorticity and that hydrodynamic models are powerful tools
      in understanding this physiopathological state.

PMID- 11291945
TI  - A few comments on electrostatic interactions in cell physiology.
AB  - The role of fixed charges present at the surface of biological membranes is
      usually described by the Gouy-Chapman-Grahame theory of the electric double-layer
      where the Grahame equation is applied independently on each side of the membrane
      and where the capacitive charges (linked to the transmembrane ionic currents) are
      disregarded. In this article, we generalize the Gouy-Chapman-Grahame theory by
      taking into account both intrinsic charges (resulting from the dissociation of
      membrane constituents) and capacitive charges, in the density value of the
      membrane surface charges. In the first part, we show that capacitive charges
      couple electrostatic potentials present on both sides of the membrane. The
      intensity of this coupling depends both on the value of the membrane specific
      capacitance and the transmembrane electric potential difference. In the second
      part, we suggest some physiological implications of membrane electric double
      layers.

PMID- 11291946
TI  - Pediatric anesthesia monitoring with the help of EEG and ECG.
AB  - This paper presents research regarding the monitoring of the brain and the
      adequacy of anesthesia during surgery. Particular variables are derived from EEG
      and ECG signals and are correlated to anesthetic gas (sevoflurane) concentration,
      in pediatric anesthesia. The methods used for parameter extraction are based on
      change detection theory and time-frequency representation. Preliminary results
      show that the expired anesthetic gas concentration modulates both the heart rate
      variability and the duration of the burst suppression. Monitors of the central
      nervous system and autonomic nervous system activities can be expected to be
      based on these variables.

PMID- 11291947
TI  - Overview of CARMEM: a new dynamic quantitative cardiac model for ECG monitoring
      and its adaptation to observed signals.
AB  - Different approaches have been proposed in order to achieve knowledge integration
      for coronary care monitoring applications, usually in the form of expert systems.
      The clinical impact of these expert systems, which are based only on "shallow"
      knowledge, has not been remarkable due to the difficulties associated with the
      construction and maintenance of a complete knowledge base. Model-based systems
      represent an alternative to these problems because they allow efficient
      integration of the "deep" knowledge on the underlying physiological phenomena
      being monitored. In this work, a brief review of existing model-based systems for
      cardiac rhythm interpretation is presented, followed by the description of a new
      system for Cardiac Arrhythmia Recognition by Model-Based ECG Matching (CARMEM).
      Fundamental characteristics of CARMEM are presented; in particular, its ability
      to provide online parameter adaptation to simulate complex rhythms and to match
      observed ECG signals. The proposed model can be useful for the explanation of the
      origin of cardiac arrhythmias and contribute towards their robust
      characterization in the context of coronary care units.

PMID- 11291948
TI  - Heritage characteristics reported by a group of African-Americans who exhibit the
      pigment dispersion syndrome: a case-control study.
AB  - PURPOSE: To investigate the racial heritage of a group of African-Americans who
      exhibit the pigment dispersion syndrome (PDS). SUBJECTS AND METHODS: Ten
      unrelated African-American PDS patients (age range 13-59) from a primary eye care
      population in Chicago, Illinois, USA, were interviewed to determine their racial
      heritage. Since Caucasian and Native American heritage were commonly reported,
      101 unaffected African-American control subjects (age range 18-55) were also
      interviewed to determine the reported frequency of these specific racial heritage
      characteristics. RESULTS: Some degree of Caucasian heritage was reported by 100%
      of the PDS subjects and by 46.5% of controls. Native American heritage was
      reported by 90% of the PDS subjects and by 71.3% of controls. Based on these
      data, the PDS subjects were significantly more likely to report Caucasian
      heritage (Fisher's exact test, P=0.001) but they were not significantly more
      likely to report Native American heritage (P=0.282). In addition, the PDS
      subjects were significantly more likely to report Caucasian heritage from both
      parents (P=0.024) and more likely to report a combination of both Caucasian and
      Native American heritage (P=0.0006) than corresponding controls. In general, the
      PDS subjects had 'light' or 'medium' complexions. CONCLUSION: Results from this
      analysis are consistent with the hypothesis that non-African heritage,
      particularly Caucasian, is likely to be prevalent in the background of African
      Americans who exhibit PDS. It is suggested that non-African heritage may not only
      be important for the transference of PDS causing genes, but it may also influence
      factors such as degree of iris pigmentation and rigidity which could influence
      iris contour and the subsequent expression of PDS in those who are genetically
      predisposed. Further investigation is needed to study the factors that influence
      the expression and severity of PDS among African-Americans, a population which
      traditionally has been considered to be rarely affected by this condition.

PMID- 11291949
TI  - Impact of notch filter use on waveforms of First- and Second-Order-Kernel
      responses from multifocal ERGs.
AB  - The filter settings of the amplifier section of ERG recording systems have large
      impact on the waveforms of the recorded responses. In this study, the effects of
      a 50 Hz notch filter were assessed for both First-Order-Kernel- (FOK) and Second
      Order-Kernel-responses (SOK 1st slice) from multifocal ERGs recorded with a VERIS
      III system. Amplitude and phase responses of the amplifier section were recorded
      for typical filter settings with the notch filter active and inactive. Multifocal
      ERGs (MERGs) from a group of 11 normal subjects were recorded for both amplifier
      settings, the waveforms resulted from those recordings were compared in the time
      and frequency domain. To verify the results, the recordings without the notch
      filter were digitally filtered with a simulated notch filter and compared to the
      responses recorded with an active analog notch filter. The line filter has the
      biggest attenuation at 50 Hz with an additional phase jump of 180 degrees. The
      FOK responses of MERGs are assembled by frequencies below 65 Hz with main
      spectral components between 19 and 47 Hz. The 1st slice of the SOK consists of
      frequencies up to 100 Hz with main components between 19 and 84 Hz. Thus, if FOK
      recordings are to be analyzed, the notch filter of the amplifier can be used in
      order to cope with noise problems caused by the line frequency of 50 Hz. However,
      one must be aware that the attenuation of higher frequency components will lead
      to changes of the waveforms. For SOK analysis, main spectral components are
      attenuated and/or shifted in phase, which leads to completely different waveforms
      and severe distortion of the recording results.

PMID- 11291950
TI  - Role of electroretinography in the assessment of retinal function as an indicator
      of vitamin A status.
AB  - Hypovitaminosis A is associated with exocrine pancreatic insufficiency in cystic
      fibrosis. Peripheral retinal dysfunction is an early finding of vitamin A
      deficiency. We evaluated serum retinol and zinc as well as visual adaptation in
      41 patients with cystic fibrosis, receiving generous pancreatic enzyme and
      micronutrient supplementation. Forty-one normal individuals matched for age and
      sex served as controls. Peripheral retinal function was measured by clinical
      electroretinography using an Electrophysiologic Personal Interfaced Computer and
      applying a standard protocol. Serum retinol in cystic fibrosis was significantly
      lower than that of the control group (0.30+/-0.01 versus 0.39+/-0.02 mg/l,
      p<0.001). Serum zinc concentrations were normal in the cystic fibrosis group
      (1.21+/-0.03 mg/l) and significantly higher than that of the control group
      (1.02+/-0.01 mg/l, p<0.001). The overall visual adaptation, however, was found to
      be normal and comparable in the two groups. It is concluded that, in cystic
      fibrosis, despite appropriate vitamin A supplementation, retinol serum
      concentration may be low. As serum retinol does not reflect vitamin A status,
      evaluation of visual adaptation may be a more appropriate way to monitor for
      vitamin A deficiency in cystic fibrosis.

PMID- 11291951
TI  - Might and magic, lust and language--the eye as a metaphor in literature. Notes on
      the hierarchy of the senses.
AB  - The special anatomy and physiology of the eye predestine it to function as the
      primary mediator between the world within us and the world without. The way we
      respond to and reflect on our world is strongly associated with our eyesight.
      Since antiquity literature, the most important medium for propagating knowledge,
      has abounded with symbols for the motif 'eye,' symbolizing the responsibility,
      independence and significance of the visual sense. Today the mechanisms of the
      modern information media engulf us with new and permanent stimuli. If we
      surrender ourselves uncritically to this profusion of images, we risk
      'overstraining' our sense of sight and losing the connection between perception
      and cognition. In the following a few references to the international non-medical
      literature may explain and illustrate the functions of the eye as a metaphor for
      the mind and describe the past and the prospects of visual perception.

PMID- 11291952
TI  - Fourier analysis of steady-state visual evoked potentials in subjects with normal
      and defective stereo vision.
AB  - The purpose of this work was to study the second harmonic in the steady state
      pattern visual evoked potential (ssVEP) to various stimulus frequencies in
      subjects with normal and defective binocularity. ssVEPs were elicited by 4 c/deg
      sinusoidal gratings, with temporal frequencies ranging from 5 to 20 Hz (exp. 1)
      and 15 to 27.5 Hz (exp. 2). Responses were Fourier analysed and power and phase
      of the second harmonic to stimulus frequency were measured. For power, binocular
      enhancement in a bimodal fashion was found both in normals and in subjects with
      defective binocularity. The power with binocular stimulation was significantly
      higher in the normal group in the high frequency domain. Latency, estimated from
      the phase-frequency function, was longer in the group with defective
      binocularity, but this was statistically significant only for the high frequency
      domain. The results suggest that a visual system with normal binocular function
      can follow a stimulus with high temporal frequency more accurately than a system
      with disturbed binocularity.

PMID- 11291953
TI  - The effect of time of day and repeat reliability on the fast flicker multifocal
      ERG.
AB  - PURPOSE: To investigate the possible influence of different times of the day on
      multifocal ERG recordings in normals. METHODS: 10 healthy volunteers underwent
      multifocal ERG recordings (VERIS 3.1.1.) 3 times a day, at 10:30 am, 1:30 pm and
      4:30 pm using a fast flicker stimulus of 103 hexagons. Additional night-time
      recordings were performed in 2 subjects. The first-order and dominant part of the
      second order response component were analyzed. RESULTS: Neither peak latencies
      nor peak-to-peak amplitudes showed significant changes during the day (p >0.05).
      Comparison between night and day time recordings did also not reveal an influence
      of a circadian rhythm on the MF-ERG. CONCLUSIONS: No significant influence of the
      time of the day suggestive of a circadian rhythm could be observed. Light
      adaptation due to preadaptation and the flicker sequence used could be a possible
      cause for these results.

PMID- 11291958
TI  - Organic components of crystal sheaths in bones.
AB  - Crystals in bones are enveloped within organic crystal sheaths of 5-10 nm widths.
      In order to analyse their components, we investigated the immunolocalizations of
      chondroitin 4- and 6-sulphate, keratan sulphate, bone sialoprotein and
      osteopontin. All of these, except chondroitin 6-sulphate, were found in bone
      matrix. Although the localizations of chondroitin 4-sulphate and keratan sulphate
      tended to focus within calcified nodules, bone sialoprotein and osteopontin were
      widely distributed in the area, being linearly arranged along electron-dense
      structures corresponding to crystal sheaths. These two proteins possess the
      ability to affect nucleation or elongation of hydroxyapatite, positively or
      negatively, in vitro. Our results suggested that bone sialoprotein and
      osteopontin may combine to form the crystal sheaths which are thought to control
      crystal formation and growth, using the seemingly opposite functions of bone
      sialoprotein and osteopontin.

PMID- 11291959
TI  - Synergy of lysozyme and lanoconazole on the morphology of Candida albicans.
AB  - Synergism of lysozyme with the imidazole antifungal lanoconazole (LCZ) has been
      demonstrated in vitro against Candida albicans. To determine the mechanism of the
      synergistic action, the effects of subinhibitory concentrations of lysozyme (50
      microg ml(-1)) and LCZ (1.25 microg ml(-1)), used alone and in combination, on
      the morphology and ultrastructure of C. albicans cells were studied by
      fluorescence microscopy using Fungiflora Y, as well as by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). In the presence of
      lysozyme, the separation of apparently mature cells from each other was
      inhibited, and cells in which cell wall-like material had markedly accumulated in
      the periplasmic space were frequently observed. Such intracellular
      ultrastructural changes were not seen in LCZ-treated cells, but normal septal
      wall biogenesis was inhibited with the resultant formation of long chains of
      interconnecting cells. When the cultures were treated with the combination of
      lysozyme and LCZ, intracellular accumulation of cell wall-like materials
      increased in extent, and the peripheral wall structure was severely damaged.
      These morphological and ultrastructural findings lead us to the following
      conclusions: (1) lysozyme and LCZ inhibit the process of cell division in
      different manners; (2) lysozyme appears to affect cell wall formation more
      directly and drastically by interrupting the normal assembly and integration of
      cell wall components; and (3) these effects of lysozyme are noticeably enhanced
      when combined with LCZ.

PMID- 11291960
TI  - Three-dimensional reconstruction by scanning electron microscopy from serial
      epoxy resin semi-thin sections after ion-etching.
AB  - Three-dimensional reconstruction was performed using scanning electron
      micrographs of serial semi-thin sections of Epon embedded specimens. Connective
      tissue in a rabbit ear chamber was fixed in glutaraldehyde and osmium tetroxide,
      and then embedded in Epon. One-microm-thick serial sections were cut with a
      diamond knife, mounted on glass slides and stained with toluidine blue. After
      observation with a light microscope, the sections were ion-etched with an ion
      spatter coater. Following double staining with uranyl acetate and lead citrate,
      the consecutive sections were ion-coated with platinum. Each serial section was
      photographed with a scanning electron microscope. Profiles of a blood vessel and
      fibroblasts were digitized with a computer and computer reconstruction of the
      blood vessel was performed. Three-dimensional reconstructions showed that the
      newly formed blood vessel was a cylinder-like, bare endothelial tube with a
      rather smooth outer surface. Fibroblasts were situated around the endothelial
      tube. Several openings were found in the endothelial tube, suggesting the
      morphological feature of high permeability and fragility in newly formed blood
      vessels. The availability of three-dimensional reconstruction from scanning
      electron micrographs of serial semi-thin epoxy resin sections was discussed;
      structures of interest can be reconstructed (1) quickly and easily, (2) without
      skilful techniques, and (3) almost at the level of ultrastructure.

PMID- 11291961
TI  - Effects of brushing with a dentifrice for sensitive teeth on tubule occlusion and
      abrasion of dentin.
AB  - By using a dentifrice or toothpaste for sensitive teeth, the brushing-induced
      effects on dentinal tubule occlusion and abrasion of human sound dentin were
      investigated with a scanning electron microscope and a scanning laser microscope.
      The dentifrice contained diatomaceous earth and silica as abrasives and strontium
      chloride hexahydrate as an active ingredient. Thirty dentin pieces of human
      premolar teeth with an average of 20% occluded dentinal tubules were attached to
      resin plates and exposed to the oral cavities of five adult subjects for 2, 4,
      and 8 weeks. Brushing with and without dentifrice was performed 1 min per day,
      respectively. Brushing with the dentifrice gradually decreased the mean average
      of occluded tubules from about 91 to 77% during 2 to 8 weeks, although there were
      no significant differences among the individual values. However, the mean
      abrasive loss of the dentin surfaces brushed with dentifrice significantly
      increased from about 52 to 143 microm in depth. The brushed surfaces of the
      dentin showed a rough topography with numerous toothbrush scratches but no
      organic pellicle was found. On the other hand, brushing without dentifrice caused
      about 99% of the dentinal tubules to occlude in 2 and 4 weeks and 100% in 8
      weeks. The brushed dentin surfaces at 8 weeks were entirely covered with organic
      pellicle containing fine mineral granules derived from saliva, and the abrasive
      loss was about 1.4 microm in mean depth. Such results indicate that brushing with
      abrasive dentifrices for sensitive teeth remarkably erodes dentin, and suggest
      that the brushing should cause the dentinal tubules to open again for a certain
      period of time.

PMID- 11291962
TI  - Scanning electron microscopic study of muscle spindles in the tenuissimus muscle
      of the Chinese hamster: with reference to the outer capsule, inner capsule and
      fusimotor endings.
AB  - The outer capsule, inner capsule and fusimotor endings of muscle spindles in the
      tenuissimus muscle of mature Chinese hamsters were examined by scanning electron
      microscopy (SEM). The thin and long tenuissimus muscle was transversely cut into
      several segments, and the segments were longitudinally or obliquely cut with a
      razor blade to mechanically remove the spindle sheath (outer capsule). These
      specimens were treated with 8 N HCl at 60 degrees C to isolate the muscle
      spindles and clearly expose the internal structures such as the inner capsule and
      fusimotor endings innervating intrafusal muscle fibers. The spindle sheath was
      about 1 mm long and at the equator about 50 microm in diameter. Within the outer
      capsule, cells of the inner capsule in the equatorial region were polygonal in
      shape, and continuously surrounded the axial bundle like a sleeve. This
      continuous sheath became sieve-like in the juxta-equatorial region, depending on
      the twining of thin and flattened cytoplasmic extensions and/or processes of the
      cells. Owing to the continuous inner capsular sheath in the equatorial region,
      the arrangement of sensory endings were not visualized under SEM. Fusimotor
      endings observed in the juxta-equatorial and polar regions consisted of poorly
      developed subneural apparatuses with predominantly pit-like and short slit-like
      junctional folds.

PMID- 11291963
TI  - An improved procedure of electron microscopic in situ hybridization for detecting
      adenovirus DNA.
AB  - Electron microscopic in situ hybridization (EM-ISH) is a useful method in
      determining the localization of a specific nucleic acid at the ultrastructural
      level. Since the EM-ISH protocol includes many steps, no standard protocol for EM
      ISH is available yet. In this study, we optimized quantitatively the critical
      conditions with respect to embedding resin, nucleic acid labeling and
      hybridization reaction time, by using adenovirus-infected cells as the indicator
      cells. The optimal detection of an adenovirus-specific nucleic acid was obtained
      by overnight hybridization reaction on sections embedded in Lowicryl K4M resin.
      Random-primed-labeled probes improved the reactivity. At least 60% of virus
      particles in paracrystalline arrays was found to contain viral DNA. These arrays
      in adenovirus-infected cells are useful in evaluating quantitatively the
      efficiency of protocols of EM-ISH.

PMID- 11291964
TI  - New method for quantitative mapping of metallic elements in tissue sections by
      electron probe microanalyser with wavelength dispersive spectrometers.
AB  - In this paper, we have proposed a new method that gives quantitative
      distributions of metallic elements in a tissue section by electron probe
      microanalyser equipped with wavelength dispersive spectrometers. Its principal
      merit is the clear expression of element distribution with micrometer resolution
      in typically prepared section samples for routine histopathological diagnosis. By
      analysing thin standard films containing metallic atoms of interest, it was
      confirmed that the detection limit is about 1 x 10(6) atoms microm-2. This value
      corresponds to 100 microg g(-1) (dry weight) in case of tissue section of 2
      microm thickness. Furthermore, for copper, iron and aluminium, the exact linear
      relationship between the amount of metallic atoms and the characteristic X-ray
      intensity was established in the range up to 15 x 10(6) atoms microm(-2). The
      element maps of tissue sections from patients with Wilson's disease proved that
      the copper levels in analysed areas were not homogeneous and indicated abnormal
      accumulation in some portions. These results confirmed the usefulness of this
      method for histopathological diagnosis.

PMID- 11291966
TI  - Late onset rheumatoid arthritis.

PMID- 11291967
TI  - Late onset rheumatoid arthritis--a clinical and laboratory study.
AB  - AIM: To analyze the clinical and laboratory profile of late onset rheumatoid
      arthritis in comparison with early onset rheumatoid arthritis. METHODS: Fifty
      patients who satisfied 1988 American College of Rheumatology criteria for
      rheumatoid arthritis with the disease onset at 60 years or over were studied.
      Handred cases of early onset rheumatoid arthritis were taken as controls. All of
      them were followed up for 18 months. RESULTS: Female to male ratio was 1.6:1 in
      late onset rheumatoid arthritis and 4:1 in early onset group. Shoulder joint
      involvement was 48% in late onset and 28% in early onset rheumatoid arthritis.
      Rheumatoid factors was positive in 36% cases in late onset compared to 60% in
      controls. Most other clinical, laboratory and radiological features were
      comparable in both the groups. CONCLUSIONS: Late onset rheumatoid arthritis is
      characterised by a less female preponderance, more shoulder joint involvement and
      more seronegativity.

PMID- 11291968
TI  - Classical polyarteritis nodosa and microscopic polyangiitis--a clinicopathologic
      study.
AB  - OBJECTIVE: To describe the clinical spectrum, laboratory features,
      histopathological findings and treatment outcome in patients with classical
      polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA). MATERIAL AND
      METHODS: Patients with PAN and MPA seen at a large teaching hospital in north
      India over a period of five years (1994-99) were included in the present study.
      RESULTS: We encountered five patients with PAN and six patients with MPA during
      the study period. Of the five patients with PAN, two had systemic disease while
      three had limited PAN. The patients with limited PAN included two with cutaneous
      PAN and one with PAN confined to the nerves. Constitutional symptoms,
      musculoskeletal complaints, peripheral neuropathy and skin lesions dominated the
      clinical picture. Fifty percent of the MPA patients presented as pulmonary renal
      syndrome. All the patients with PAN were HBsAg and ANCA negative and had normal
      urinalysis findings. In contrast, all patients with MPA demonstrated an active
      urine sediment and 83.3% were pANCA positive. Some of the rare features
      encountered by us were the presence of antiphospholipid syndrome and extensive
      interstitial lung disease in MPA, and spontaneous recovery in one patient with
      systemic PAN. Treatment outcome was better in PAN as compared with MPA.
      CONCLUSIONS: The clinical spectrum of PAN and MPA is quite varied. A good outcome
      is possible with the use of corticosteroids and cyclophosphamide.

PMID- 11291969
TI  - Pre hospital issues in acute myocardial infarction.
AB  - OBJECTIVES: Time is of prime importance in the management of acute myocardial
      infarction (AMI). Time to hospital admission should be minimised for maximum
      thrombolytic benefit. The present paper has evaluated some socio-demographic
      factors influencing pre hospital delay. METHODS: This prospective observational
      study of 1,072 patients with AMI admitted to 14 hospitals in South India was done
      over one year. Socio-demographic factors viz. time of symptom onset, place of
      residence, type of transportation to hospital, distance travelled, as well as
      clinical and treatment details were recorded. Hospitals were grouped based on
      their location into metropolitan and town hospitals. RESULTS: Males predominated
      (85%) and had AMI at a younger age than females. Most patients (74%) travelled
      less than 30 km to a hospital. The mean distance travelled to a town hospital was
      longer than that to a metropolitan hospital (24.2 km vs 21 km; p < 0.0001);
      however there was no significant difference in the type of transportation or time
      taken to reach either of the hospitals. Majority (79%) of patients arrived at a
      hospital within the thrombolytic window of 12 hours (mean time = 11 hours). The
      occurrence of a previous MI had no influence on time taken to hospital arrival,
      questioning the role of symptom education as an interventional strategy to reduce
      pre hospital delay. Patients older than 70 years and females in towns with
      symptom onset during the day (6 am to 6 pm) took a longer time to reach hospital.
      CONCLUSION: Community facilities do not affect pre hospital delay. Interventions
      should focus on reducing decision time to call for help and the role of symptom
      education needs further evaluation.

PMID- 11291970
TI  - Characterization of nonfermenters from clinical samples.
AB  - OBJECTIVE: Nonfermenters are a group of aerobic non sporing gram-negative bacilli
      found primarily free in nature and as commensals, whose pathogenic potentials are
      well established. The current study was conducted to assess the role of these
      nonfermenters in various infections and to characterize these isolates. METHODS:
      One hundred nonfermenters isolated from various clinical specimens were grouped
      according to Weaver-Hollis scheme based on growth on MacConkeys agar, oxidase
      activity and oxidation/fermentation of glucose. Species level identification was
      attempted based on a battery of biochemical tests. All isolates were then
      subjected to antimicrobial sensitivity. RESULTS: Majority of the isolates were
      encountered from pus and urine (50%). These isolates belonged to six of the seven
      Weaver-Hollis groups. Fifty six per cent of the isolates belonged to genus
      Pseudomonas. Multidrug resistance with resistance to more than three
      antimicrobials was frequently seen. Amikacin and ciprofloxacin were found to be
      most effective. CONCLUSION: Nonfermenting gram negative organisms are responsible
      for variety of infective conditions. Amongst them genus Pseudomonas and
      Acinetobacter calcoaceticus were more frequently encountered. Amikacin or
      ciprofloxacin (for nonfermenters other than Pseudomonas) appears to be the drug
      of choice for treatment of such infections.

PMID- 11291971
TI  - Comparison of antioxidant efficacy of vitamin E, vitamin C, vitamin A and fruits
      in coronary heart disease: a controlled trial.
AB  - OBJECTIVE: To determine the efficacy of various antioxidant vitamins and a major
      dietary source of antioxidants (fruits) we performed a randomized controlled
      trial. METHODS: 175 successive patients with coronary heart disease (CHD)
      presenting to our centre were recruited and using a Latin-square design divided
      into five groups of 35 each. The groups were matched for age, lifestyle and
      dietary variables, clinical diagnosis and drug treatment status. None of the
      patients was on lipid-lowering drugs. Supplemental vitamins were stopped for one
      month before study began and American Heart Association Step II dietary advice
      was given to all. At baseline, total cholesterol, triglycerides, HDL and LDL
      cholesterol and lipid peroxide measured as thiobarbaturic acid reactive
      substances (TBARS) were determined. Group I received placebo capsules; Group II
      vitamin E 400 units/day; Group III vitamin C 1,000 mg; Group IV vitamin A 25,000
      IU; Group V received 400 gm of fruit daily. Lipids and lipid peroxide levels were
      determined at 30 days follow-up. RESULTS: Response rate in various groups varied
      form 86% to 91%. No significant changes in total, HDL, LDL cholesterol and
      triglyceride levels were seen in Groups I, II, III and IV (paired t-test p >
      0.05). In Group V there was a significant decrease in total cholesterol (-7.8 +/-
      11.1%), and LDL cholesterol (-11.2 +/- 25.4%) and increase in HDL cholesterol
      (+12.9 +/- 20.1%) (paired t-test p < 0.01). Lipid peroxide levels decreased
      significantly in all the treatment groups (p < 0.01). This decrease was the
      highest in Group II (vitamin E; -36.4 +/- 17.7%) as compared to Group III
      (vitamin C -19.8 -/+ 10.8%); Group IV (vitamin A -5.4 +/- 17%) and Group V
      (fruits -13.1 +/- 12.0%). CONCLUSIONS: All the antioxidant vitamins and fruits
      significantly decrease lipid peroxide levels and oxidant load in CHD patients.
      However, fruits are the best choice as they also favourably modify the lipid
      profile.

PMID- 11291972
TI  - Value of different cut-off points of tuberculin skin test to diagnose
      tuberculosis among patients with respiratory symptoms in a chest clinic.
AB  - OBJECTIVE: To assess the utility of various cut-off points of tuberculin skin
      test in making a diagnosis of tuberculosis in patients with respiratory symptoms.
      METHODS: Tuberculin skin test was conducted on consecutive new patients attending
      chest clinic for various respiratory symptoms. All subjects were then
      investigated to establish diagnosis, and categorized into tuberculous and
      nontuberculous groups. Receiver operating characteristic (ROC) curve was plotted
      to evaluate discrimination by tuberculin skin test. Sensitivity, specificity and
      predictive value were also calculated at various cut-off points. RESULTS: Of 250
      patients, 59 (23.6%) had tuberculosis on clinical and microbiological criteria
      (other than the tuberculin test). Sensitivity and specificity of tuberculin test
      at readings greater than 5, 10 and 15 mm were 0.8136 and 0.7068, 0.6271 and
      0.8901, and 0.2034 and 0.9738 respectively. Area under ROC curve for this test
      was 0.80. CONCLUSION: A cut-off point of 10 mm is likely to be useful in
      supporting a diagnosis of tuberculosis in patients with strong clinical suspicion
      of tuberculosis, in other patients, 15 mm cut-off may be more suitable.

PMID- 11291973
TI  - Restenosis after coronary stenting--incidence and predictors.
AB  - OBJECTIVE: To determine the intermediate term outcome after coronary artery
      stenting. METHODS: The six month angiographic and clinical follow-up of 92
      consecutive patients (94 lesions) undergoing successful coronary stenting was
      performed. Multiple variables were analyzed for predicting restenosis. RESULT:
      The mean age was 49.7 +/- 8.5 years. There were 73 males and 19 females. Coronary
      artery involvement was left anterior descending artery (LAD) in 67%, left
      circumflex artery (LCx) in 16.5% and right coronary artery (RCA) in 16.5%. The
      pre-procedure mean reference diameter was 3.1 +/- 0.38 mm, minimal luminal
      diameter (MLD) was 0.47 +/- 0.28 mm and percentage diameter stenosis (DS) was 85
      +/- 9%. Post procedure MLD improved to 3.1 +/- 0.4 mm with an acute gain of 2.6
      +/- 0.4 mm and residual DS of only 3 +/- 3%. Clinical and angiographic variables
      were correlated with restenosis assessed as both binary and continuous variables.
      Angiographic follow-up could be obtained in 55 out of 92 patients (60%) and 86
      patients (88%) had a clinical follow-up. Angiographic restenosis (> 50% diameter
      stenosis) was present in 12 (22%) patients, seven of whom required a repeat
      angioplasty procedure. There was no death. At follow-up, the MLD was 2.1 +/- 0.93
      and the DS was 32 +/- 29% with a lumen loss of 0.92 +/- 0.84 mm. Only 14 (16%) of
      patients had angina and stress test was positive in 21 (23%).
      Hypercholesterolemia (p < 0.001) and female gender (p < 0.05) were independently
      associated with high lumen loss. CONCLUSION: Intracoronary stenting in an
      unselected patient group is associated with a 22% restenosis rate.
      Hypercholesterolemia and female gender are associated with higher restenosis.

PMID- 11291974
TI  - Neurological manifestations of HIV disease.
AB  - We report the results of neurological evaluation of 1,527 HIV positive subjects.
      Neurological complications were seen in 457 patients (481 neurological events).
      The prevalence was 20.24% of patients attending the out-patient clinic and in
      44.57% of in-patients. Involvement of all levels of neuraxes was documented. The
      commonest manifestations were neuropathies, including herpes zoster (28.27%),
      meningitis (17.88%) and mass lesions (16%). Cryptococcal meningitis was clearly
      commoner than tubercular meningitis (67.44% vs 18.60% of all cases of meningitis,
      respectivelv). Amongst mass lesions, 14/24 single lesions and 27/38 multiple
      lesions responded to anti-toxoplasma treatment and were diagnosed as CNS
      toxoplasmosis. In abscence of biopsy, it would be prudent to initiate empirical
      anti-toxoplasma treatment for all HIV patients with mass lesions and assess
      clinical and radiological response. To our knowledge this is the largest series
      of neurological manifestations of HIV disease documented in Indian literature.

PMID- 11291975
TI  - Post Kala-azar dermal leishmaniasis.

PMID- 11291976
TI  - Left sided pulmonary embolism mimicking non Q acute myocardial infarction.

PMID- 11291977
TI  - Postprandial hyperglycaemia--the real challenge in diabetes.

PMID- 11291978
TI  - Gestational diabetes mellitus.

PMID- 11291979
TI  - Accidental self-injection with Freund's complete adjuvant.
AB  - The case of a research worker who accidentally injected herself with Freund's
      Complete Adjuvant (FCA) in the right forearm is reported. This resulted in a
      serious granulomatous inflammation of the hand an forearm. She was treated with
      corticosteroids and chloroquine with good result. The course of this reaction and
      the hazards of injection with FCA are emphasised and the relevant literature
      reviewed.

PMID- 11291980
TI  - Discrete subvalvular aortic stenosis in adults.
AB  - Discrete subvalvular aortic stenosis is a relatively rare condition in adults. It
      is often diagnosed during first decade of life especially in association with
      other congenital malformations. Isolated form of discrete subvalvular aortic
      stenosis may however silently progress from innocent murmurs of childhood and
      adolescence to symptomatic left ventricular outflow tract obstruction in adults.
      Certain overt and subtle morphological abnormalities may underlie the initial
      expression as well as high recurrence rates after surgical resection of sub
      aortic membrane. Though surgical resection is the only treatment available,
      debate on the surgical technique and appropriate timing of surgery continues.
      Close followup with serial echocardiographic examinations in patients detected to
      have functional murmurs during childhood may be helpful in early detection of
      subvalvular aortic stertosis.

PMID- 11291981
TI  - Rhinocerebral mucormycosis in a patient of acute renal failure.
AB  - Mucormycosis is the name for invasive fungal infection caused by mucorales. The
      disease is uncommon and produces serious and rapidly fatal infection in patients
      with serious pre-existing illness. The classical presentation of rhinocerebral
      mucormycosis is involvement of nasal mucosa with invasion of paranasal sinuses
      and orbit. We report a case of mucormycosis in an otherwise healthy female who
      had developed acute renal failure following gastroenteritis.

PMID- 11291982
TI  - Mumps with cerebellar encephalitis.
AB  - A 30 years male patient, having typical symptoms of mumps, presented with acute
      cerebellar ataxia two days after the onset of parotid enlargement. The
      neurological symptoms showed complete recovery over the subsequent six weeks,
      suggestive of para-infectious cerebellar demyelination due to mumps.

PMID- 11291983
TI  - Disseminated cryptococcal infection in immune competent patients.
AB  - Cryptococcal meningeal or cerebral infection has become an increasing global
      problem.(1) In this respect there are many anacedotal Indian case reports.(2)
      More than 50% of CNS infections occur in immunosuppressed patients and other
      debilitating conditions. Neurological form of cryptococcosis in immunocompetant
      patients needs to be considered in situations with intractable headache,
      papilloedema, hydrocephalus and prior to decisions on shunt placements.(3) We
      report on two such immunocompetent patients who presented with CNS involvement.
      Their clinical features and outcome is discussed.

PMID- 11291984
TI  - A man with absent gallbladder.

PMID- 11291985
TI  - Apical pulmonary tuberculosis presenting with Pancoast syndrome like features.

PMID- 11291986
TI  - Amantadine treatment in cerebellar ataxia.

PMID- 11291987
TI  - Priapism in type 2 diabetes mellitus.

PMID- 11291988
TI  - Guillain-Barre syndrome following antirabies semple vaccine--a report of six
      cases.

PMID- 11291989
TI  - Atypical presentation of Sheehan's syndrome without postpartum haemorrhage.

PMID- 11291990
TI  - Diarrhoeal infection with Aeromonas species.

PMID- 11291991
TI  - Clinical profile of HIV in rural Western Maharashtra.

PMID- 11291992
TI  - Unusual clinical manifestations of acute pneumonia.

PMID- 11291993
TI  - Evaluation of Siddha medicare in HIV disease.

PMID- 11291994
TI  - Impaired fasting glucose versus impaired glucose tolerance.

PMID- 11291995
TI  - Herpes simplex virus-1 encephalitis in eastern UP.

PMID- 11291996
TI  - Biostatistician as a referee for a biomedical journal.

PMID- 11291997
TI  - Sedation for cataract surgery.

PMID- 11291998
TI  - Orphanin FQ/nociceptin attenuates motor stimulation and changes in nucleus
      accumbens extracellular dopamine induced by cocaine in rats.
AB  - RATIONALE: Orphanin FQ (OFQ; also known as nociceptin), the endogenous ligand of
      the opioid receptor-like receptor, injected intracerebroventricularly (i.c.v.)
      decreases basal motor activity and basal extracellular levels of dopamine (DA) in
      the nucleus accumbens (Nuc Acc) in rats. OBJECTIVE: The present study was
      designed to determine if OFQ similarly attenuates cocaine-induced motor
      stimulation and to determine if this effect is dependent on attenuation of the
      increase in extracellular DA. METHODS: After a 1-h adaptation period, rats were
      injected with either artificial cerebrospinal fluid or OFQ (3-30 nmol, i.c.v.) 5
      min prior to cocaine (10 mg/kg, i.p.) or apomorphine (3 mg/kg, i.p.)
      administration and the total distance traveled was measured for a further 1 h. In
      a separate experiment, changes in extracellular DA were monitored by
      microdialysis following cocaine and OFQ treatment in anesthetized rats. RESULTS:
      OFQ dose-dependently attenuated both basal and cocaine-induced motor stimulation.
      OFQ (30 nmol, i.c.v.) also attenuated both the basal and the cocaine-induced
      increase in extracellular DA in the Nuc Acc. OFQ, at the highest dose, also
      decreased the motor stimulation induced by apomorphine. CONCLUSIONS: Our results
      suggest that the modulatory effect of OFQ on locomotor activity is not solely due
      to its inhibitory action on extracellular DA in the Nuc Acc.

PMID- 11291999
TI  - Tyrosine depletion attenuates dopamine function in healthy volunteers.
AB  - RATIONALE: Tyrosine depletion has been shown to reduce dopamine over activity in
      animal and human investigations. However, the effects on basal dopamine function
      have not been explored. Such information could establish tyrosine depletion as an
      effective probe of dopamine function in healthy volunteers and would also have
      relevance for future therapeutic applications of this manipulation. OBJECTIVE:
      The present study investigated the effect of acute tyrosine depletion on dopamine
      function in healthy volunteers using a combination of neuroendocrine,
      neuropsychological and subjective measures. METHODS: On one occasion, volunteers
      received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR
      free), whilst on the other they received a balanced (BAL) amino acid drink.
      Plasma prolactin, amino acid levels and subjective state were monitored over 6 h
      following the two drinks, and volunteers also completed a battery of tests from
      the CANTAB, including measures of spatial memory previously found to be sensitive
      to changes in dopamine function. RESULTS: Plasma prolactin levels rose following
      the TYR-free drink relative to the balanced mixture, indicative of decreased
      dopamine neurotransmission within the hypothalamus. Following the TYR-free drink,
      volunteers were impaired at spatial recognition memory and spatial working
      memory. Volunteers also tended to report that they felt less good following the
      TYR-free than the BAL mixture. CONCLUSION: Tyrosine depletion in healthy
      volunteers affected baseline dopamine function on the different measures employed
      in this study. Tyrosine depletion would thereby seem valuable as a probe of
      dopamine function in human volunteers. Ratings of depression and other aspects of
      cognitive function were unaffected, suggesting that this manipulation may be free
      of significant side effects when used as a treatment for conditions characterised
      by dopamine over activity, such as acute mania and schizophrenia.

PMID- 11292000
TI  - Dose relationship of limbic-cortical D2-dopamine receptor occupancy with
      risperidone.
AB  - RATIONALE: It has been suggested that the antipsychotic effect of antipsychotics
      is mediated by the antagonism of the dopamine D2 receptor in the limbic-cortical
      regions. Risperidone has an atypical property, but its effect on limbic-cortical
      regions has not been evaluated. OBJECTIVES: In this study, we examined the
      relationship among doses of risperidone and limbic-cortical dopamine D2 receptor
      occupancy using positron emission tomography. METHODS: Seven patients with
      schizophrenia were scanned during the steady state with risperidone. Their
      occupancies in limbic-cortical regions were determined using positron emission
      tomography with [11C]FLB 457. RESULTS: The average occupancy ranged from 38% to
      80% on doses of 1-6 mg/day. The saturation curve plotted against the drug level
      fit the data well. CONCLUSIONS: Our results demonstrate that the D2 receptor
      occupancy with risperidone in the limbic-cortical regions seems to be similar to
      that of previous reports regarding the striatum, and it would be comparable to
      that of typical antipsychotics.

PMID- 11292001
TI  - The discriminative stimulus properties of self-administered ethanol are mediated
      by GABA(A) and NMDA receptors in rats.
AB  - RATIONALE: The neurobiological systems that mediate the discriminative stimulus
      effects of self-administered drugs are largely unknown. The present study
      examined the discriminative stimulus effects of self-administered ethanol.
      METHODS: Rats were trained to discriminate ethanol (1 g/kg, IP) from saline on a
      two-lever drug discrimination task with sucrose (10% w/v) reinforcement. Test
      sessions were conducted with ethanol (0 or 10% v/v) added to the sucrose
      reinforcement to determine if self-administered ethanol would interact with the
      discriminative stimulus effects of investigator-administered ethanol, or with the
      ethanol-like discriminative stimulus effects of the GABAA-positive modulator
      pentobarbital or the non-competitive NMDA antagonist MK-801. RESULTS: During a
      saline test session, ethanol (10% v/v) was added to the sucrose reinforcement.
      Responding by all animals began accurately on the saline-appropriate lever and
      then switched to the ethanol-appropriate lever after rats self-administered a
      mean dose of 1.2 +/- 0.14 g/kg ethanol. During cumulative self-administration
      trials, responding initially occurred on the saline lever and then switched to
      the ethanol-appropriate lever after ethanol (0.68 +/- 0.13 g/kg) was self
      administered. Investigator-administered MK-801 (0.01-1.0 mg/kg, cumulative IP)
      and pentobarbital (0.3-10.0 mg/kg, cumulative IP) dose-dependently substituted
      for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801
      and pentobarbital dose-response curves were shifted significantly to the left.
      CONCLUSIONS: Self-administered ethanol substituted for and potentiated the
      stimulus effects of investigator-administered ethanol, suggesting that the
      discriminative stimulus effects of self-administered ethanol are similar to those
      produced by investigator-administered ethanol. Self-administered ethanol enhanced
      the ethanol-like discriminative stimulus effects of MK-801 and pentobarbital,
      which suggests that the discriminative stimulus effects of self-administered
      ethanol are mediated by NMDA and GABAA receptors.

PMID- 11292002
TI  - Combining ondansetron and naltrexone reduces craving among biologically
      predisposed alcoholics: preliminary clinical evidence.
AB  - RATIONALE: Previously, we have reported that the combination of ondansetron (a 5
      HT3 antagonist) and naltrexone (a mu opioid antagonist) appears to act
      synergistically at improving the drinking outcomes of early onset alcoholics
      (EOA). a subtype of alcoholic characterized by developing problem-drinking
      earlier, antisocial behaviors, high familial loading, and biological disease
      predisposition. Presumably, this medication combination counteracts the
      interaction between activated central 5-HT3 receptors and the endogenous opioid
      system during the mediation of alcohol-induced reward. We now hypothesize further
      that an important mechanism by which the combination diminishes alcohol
      consumption is through a reduction in craving. OBJECTIVE: To determine whether
      the combination of naltrexone and ondansetron is superior to a placebo at
      reducing craving among EOA, and the relationship between craving and drinking
      behavior in both treatment groups. METHODS: We conducted an 8-week double-blind
      placebo-controlled clinical trial in which 10 EOA were randomized to receive
      ondansetron (4 microg/kg b.i.d.) + naltrexone (25 mg b.i.d.) and 10 EOA had a
      placebo (total n=20) as an adjunct to weekly standardized group cognitive
      behavioral therapy. Craving was measured by using the obsessive compulsive
      drinking scale (OCDS). RESULTS: Craving ratings were scored on four subscales
      which where derived empirically by principal component structure analysis of the
      OCDS. EOA who received the medication combination, compared with the placebo, had
      significantly lower scores on "automaticity of drinking" and "alcohol consumption
      ". Reduction in automaticity of drinking was correlated with self-reported
      drinking for only the medication combination group. CONCLUSIONS: By reducing
      automaticity of drinking, the medication combination presumably decreased
      drinking salience and intensity. Larger scale studies testing these medications,
      both alone and together, among alcoholic subtypes are needed to establish and
      extend these promising findings.

PMID- 11292003
TI  - Buprenorphine sublingual tablets: effects on IV heroin self-administration by
      humans.
AB  - RATIONALE: Studies have shown that buprenorphine, a partial mu opioid agonist,
      effectively reduces heroin taking. While previous research with buprenorphine
      utilized a liquid formulation, a tablet formulation is proposed for clinical use.
      However, because recent research suggests that the liquid and tablet differ in
      bio-availability, it is unclear what dose of the buprenorphine tablet effectively
      antagonizes the reinforcing effects of heroin. OBJECTIVE: The present study was
      designed to compare the effects of two sublingual doses of buprenorphine
      maintenance on heroin self-administration. METHODS: Eight heroin-dependent men
      participated in a 6-week, double-blind, placebo-controlled inpatient study to
      evaluate the reinforcing effects of intravenous heroin (0, 6.25, 12.5, 25 mg)
      during maintenance on 8 or 16 mg sublingual buprenorphine. Participants first
      sampled the available dose of heroin, and then were allowed to respond under a
      progressive ratio schedule for either heroin or $20. For each heroin dose, one
      sample session and three choice sessions occurred. Two sessions per day were
      conducted. A sample session was followed by the first choice session on one day,
      and the second and third choice sessions occurred on the following day. These
      sessions were conducted while participants were maintained on daily doses of 8 or
      16 mg buprenorphine (3 weeks each). RESULTS: Relative to placebo, 12.5 and 25 mg
      heroin produced significant increases in break point values under both
      maintenance dose conditions. The mean break point value for 12.5 mg heroin was
      significantly lower under 16 mg buprenorphine, compared to 8 mg. CONCLUSIONS:
      These results demonstrate that the reinforcing effects of heroin were not fully
      antagonized by these doses of the tablet formulation of buprenorphine, and that
      16 mg buprenorphine reduced heroin self-administration relative to 8 mg.

PMID- 11292004
TI  - Pharmacokinetic interaction between imipramine and carbamazepine in patients with
      major depression.
AB  - RATIONALE: Despite the fact that carbamazepine (CBZ) is frequently added to the
      existing tricyclic antidepressant (TCA) therapy, to date little is known about
      serum levels of pharmacologically active hydroxy metabolites of TCAs, as well as
      about possible changes in free (non-protein-bound) concentrations of these drugs
      and their metabolites during such combination treatment of depression. OBJECTIVE:
      The aim of this study was to evaluate the effect of CBZ on steady-state total and
      free serum concentrations of imipramine (IMI) and its metabolites, desipramine
      (DMI), 2-hydroxyimipramine and 2-hydroxydesipramnine, in depressed patients. In
      addition, the free and total serum concentrations of CBZ and 10,11
      epoxycarbamazepine were measured. METHOD: Thirteen patients with DSM-III-R
      diagnosis of major depression were enrolled in the study. All patients
      hospitalised at the Department of Psychiatry, Collegium Medicum, Jagiellonian
      University were treated with IMI at a dose of 2 mg/kg per day for 3 weeks, after
      which CBZ at a dose of 400 mg/day was added. Steady-state serum concentrations of
      IMI, CBZ and their metabolites were assayed by HPLC. Free drug concentrations
      were measured by ultrafiltration. RESULTS: After 2 weeks of combination therapy a
      significant decrease in mean steady-state total serum concentrations of IMI (from
      168.84 +/- 102.18 to 98.12 +/- 43.79 ng/ml) and DMI (from 293.89 +/- 171.93 to
      221.85 +/- 153.21 ng/ml) was observed. Simultaneously, steady-state serum
      concentrations of total hydroxy metabolites and free IMI and its metabolites,
      measured just before and 2 weeks after CBZ were started, did not differ
      significantly. In consequence, a significant increase in free fraction of the
      parent drug was observed (3.36 +/- 3.24% vs 5.75 +/- 3.60%). Also free fraction
      of DMI tended to be higher after CBZ addition. CONCLUSION: CBZ affects not only
      the metabolism of IMI and its metabolites, but also their protein binding.
      Therefore, despite considerable reductions in total serum levels of IMI and DMI,
      but when the unchanged free fraction concentration of these compounds is
      maintained, a dosage elevation of IMI does not seem to be necessary after CBZ
      addition to TCA therapy.

PMID- 11292005
TI  - Ethanol consumption and reward are decreased in mu-opiate receptor knockout mice.
AB  - RATIONALE: Differences in mu-opiate receptor (MOR) gene expression may modulate
      the rewarding effects of ethanol. OBJECTIVE: The effects of MOR gene knockout
      (KO) were examined in wild-type (+/+), heterozygote MOR KO (+/-), and homozygote
      MOR KO (-/-) mice on voluntary ethanol consumption, conditioned place preference
      produced by ethanol, and locomotor responses to ethanol in separate groups of
      mice. METHODS: Voluntary ethanol consumption (2-32% v/v) was examined in a two
      bottle home-cage consumption test. The conditioned place preference paradigm was
      a biased design. Mice received four pairings of ethanol (2.0 g/kg IP) on the
      initially preferred side and four pairings on the initially non-preferred side
      with saline. The difference in time spent on the initially non-preferred side
      (pre- versus post-conditioning) was the measure of drug-induced preference. After
      habituation to a novel locomotor test chamber mice were tested, on subsequent
      sessions, for ethanol induced locomotion (0.0, 0.5, 1.0, and 2.0 g/kg IP).
      RESULTS: Heterozygous and homozygous MOR KO mice consumed less ethanol than wild
      type mice. These effects appeared to be greater in female KO mice than in male KO
      mice. MOR KO mice, especially females, exhibited less ethanol reward in a
      conditioned place preference paradigm. These effects on ethanol reward were
      produced by reductions in MOR expression levels as small as 50%. MOR KO mice
      exhibited less ethanol-stimulated locomotion than did wild-type mice, an effect
      that was also largest in females. CONCLUSIONS: These data fit with the reported
      therapeutic efficacy of MOR antagonists in the treatment of human alcoholism.
      Allelic variants that confer differing levels of MOR expression could provide
      different degrees of risk for alcoholism.

PMID- 11292006
TI  - Chronic treatment with the atypical antidepressant tianeptine attenuates sickness
      behavior induced by peripheral but not central lipopolysaccharide and interleukin
      1beta in the rat.
AB  - RATIONALE: The hypothesis that proinflammatory cytokines play a causative role in
      the pathophysiology of depression has been recently tested by studying the effect
      of antidepressants on production of endogenous cytokines, and on sickness
      behavior induced by exogenous cytokines. In this last case, however, the effect
      of antidepressants has been only studied on the effect of peripherally
      administered cytokines. OBJECTIVES: The aim of the present study was to determine
      whether the antidepressant tianeptine can attenuate both peripheral and central
      cytokine actions. METHODS: Rats were injected IP with acute (10 mg/kg) or chronic
      (10 mg/kg, 2 times/day, 17 days) tianeptine. The effects of this treatment were
      assessed on the behavioral (social exploration, locomotion) and metabolic (food
      intake, body weight) alterations induced by peripheral or central administration
      of the cytokine inducer lipopolysaccharide (LPS) (250 microg/kg IP; 100 ng/rat
      ICV) or the prototypical proinflammatory cytokine interleukin-1 (IL-1)beta (15
      microg/rat IP; 90 ng/rat ICV). RESULTS: Chronic, but not acute, treatment with
      tianeptine attenuated the behavioral signs of sickness behavior induced by
      peripheral, but not central, LPS or IL-1beta. CONCLUSIONS: This work, which is
      the first in vivo study assessing the effect of an antidepressant on centrally
      induced immune activation, shows a clear dissociation between peripheral and
      central cytokine effects, and suggests a peripheral site of action of tianeptine.
      It also provides the first evidence that the protective effects of classical
      antidepressants on LPS-induced sickness behavior extend to an atypical
      antidepressant, and that the protective effect of antidepressants also applies to
      IL-1beta.

PMID- 11292007
TI  - Acute effects of alcohol on divided and covert attention in men.
AB  - RATIONALE: While several studies identified divided attention to be sensitive to
      alcohol effects, the impact of alcohol on covert visual attention is still not
      clear, despite the latter's important role in perception. OBJECTIVES: The study
      tests the effect of acute moderate doses of alcohol on divided and covert
      attention in right-handed, male volunteers. METHODS: The design of the study
      involved a double-blind trial with an alcohol and a placebo condition;
      measurements were taken before and after an oral dose of 0.6 g/kg alcohol versus
      placebo. In the divided-attention task, simultaneous visuo-spatial and auditory
      stimulation was applied. In a test of covert attention, subjects had to shift
      their attentional focus according to a central cue, from one location in the
      visual field to another. RESULTS: Under the divided-attention condition, reaction
      times were significantly prolonged after alcohol ingestion compared to placebo.
      Covert attention pre-post change was also significantly different between the
      alcohol and placebo groups. There is a reduction of false-cueing disturbance for
      left-appearing stimuli under moderate alcohol but an increase of disturbance for
      rightward stimuli, i.e. we found a lateralised pattern of reaction for spatial
      orienting. In the placebo group, no significant differences in right-left
      performance were obtained. CONCLUSION: The results suggest that sensory
      attentional mechanisms play a key role in altered visual perceptual performance
      after alcohol ingestion. Furthermore, differences between the right and left
      visual field in the cued target-detection task indicate that alcohol exerts an
      influence on right-hemispheric attentional priming.

PMID- 11292008
TI  - Discriminative stimulus effects of centrally administered isoproterenol in rats:
      mediation by beta-1 adrenergic receptors.
AB  - RATIONALE: Centrally active beta-1 and beta-2 adrenergic agonists produce
      antidepressant-like effects in several behavioral tests, suggesting that these
      receptors may be involved in the mediation of the effects of antidepressant
      drugs. OBJECTIVES: This study aimed to evaluate the ability of intra-cerebral
      ventricular (ICV) isoproterenol to produce discriminative stimulus effects
      mediated by beta adrenergic receptors, establishing a reliable model of in vivo
      activation of central beta adrenergic receptors. METHODS: Rats were trained to
      discriminate the non-selective beta adrenergic agonist isoproterenol (10 microg
      ICV) from artificial cerebral spinal fluid (aCSF) using a water-reinforced two
      lever operant task [fixed ratio-10 schedule of reinforcement (FR10)]. For
      substitution and antagonism tests, drugs were administered IP. RESULTS: Following
      acquisition of the discrimination, ICV isoproterenol produced dose-related
      increases in drug-appropriate responding (ED50 = 1.14 microg). The beta-1
      selective adrenergic agonist dobutamine fully substituted for isoproterenol at a
      dose of 0.3 mg/kg (ED50 = 0.15 mg/kg). By contrast, the beta-2 selective
      adrenergic agonist clenbuterol produced 20% isoproterenol-appropriate responding
      when administered at doses up to 0.1 mg/kg. The beta adrenergic antagonist
      propranolol fully antagonized the isoproterenol cue at a dose of 0.03 mg/kg (ID50
      = 0.013 mg/kg). The beta-1 selective antagonist betaxolol (ID50 = 0.03 mg/kg)
      more potently antagonized isoproterenol's cue than did the beta-2 selective
      antagonist ICI 118,551 (ID50 = 0.41 mg/kg). The antidepressant desipramine (1.0
      mg/kg) substituted for isoproterenol. CONCLUSIONS: These results demonstrate that
      the discriminative stimulus effects of isoproterenol are mediated primarily via
      beta-1 adrenergic receptors. This provides a functional model for activation of
      central beta-1 adrenergic receptors, permitting further characterization of the
      role of this receptor subtype in the mechanism of action of antidepressant drugs.

PMID- 11292009
TI  - Effect of intravenous injection speed on responses to cocaine and hydromorphone
      in humans.
AB  - RATIONALE: It is commonly accepted that the relative abuse liability of drugs is
      positively related to the rate of delivery to the central nervous system;
      however, few controlled studies have tested this hypothesis in humans.
      OBJECTIVES: The aims of this study were to evaluate systematically the effects of
      modifying intravenous infusion speed on the pharmacodynamic responses related to
      abuse liability and toxicity of intravenous cocaine and hydromorphone. METHODS:
      Twelve experienced opiate and cocaine users completed this 3-week inpatient
      study. After completing a safety session, participants were tested on 9 separate
      test days with intravenous cocaine (30 mg/70 kg), hydromorphone (3 mg/70 kg), and
      placebo, each administered under double-blind and randomized conditions at
      infusion rates of 2, 15, and 60 s. Dependent outcome measures included a range of
      physiological, subjective, and observer-rated measures, and continuous
      electrocardiographic monitoring was conducted for safety monitoring. RESULTS:
      Subjective responses to cocaine (for example, "high," "liking") were
      significantly greater when cocaine was infused more rapidly. Physiological
      responses to cocaine were largely unaltered with no evidence of increased
      toxicity with faster infusion speeds. None of the effects of hydromorphone were
      altered by varying the speed of infusion. CONCLUSIONS: This study provides
      empirical evidence for the commonly accepted belief that the abuse liability of
      cocaine can be enhanced by increasing the rate of the intravenous infusion; this
      principal may not hold true for opioids but further work would be required to
      rule this out. The data also indicate that moderate doses of cocaine can be
      administered over a range of infusion speeds commonly used in experimental
      settings without appreciably altering the apparent medical risks.

PMID- 11292010
TI  - Nicotine-induced enhancements in the five-choice serial reaction time task in
      rats are strain-dependent.
AB  - RATIONALE: Clinically, nicotine improves attention, but this has proven difficult
      to demonstrate preclinically. We tested nicotine in Sprague-Dawley (SD) and
      Lister hooded (LH) rats in the five-choice serial reaction time task. Since SD
      rats demonstrate lower asymptotic performance than LH rats, we surmised that
      nicotine would only improve performance in this strain. METHODS: Rats were placed
      in operant chambers 10 min after nicotine treatment (0.001-0.2 mg/kg). RESULTS:
      Nicotine dose-dependently increased correct responses only in SD rats
      (approximately 20% at the highest dose). By contrast, nicotine dose-dependently
      increased omission errors and reduced trials completed in both strains of rat,
      and dose-dependently reduced tray responses in SD rats. CONCLUSION: The magnitude
      of improvement in accuracy seen with nicotine in SD rats is greater than
      previously demonstrated using lesion or parametric manipulation models in other
      strains of rat in this test of attention. Although this suggests that the SD
      strain may be a useful "tool" for future studies, other task parameters, such as
      stimulus duration, may have to be optimum to demonstrate the magnitude of
      improvement observed presently.

PMID- 11292011
TI  - Subjective effects and tolerability of the South American psychoactive beverage
      Ayahuasca in healthy volunteers.
AB  - RATIONALE: Ayahuasca is a South American psychoactive beverage that contains the
      naturally occurring psychedelic agent N,N-dimethyltryptamine (DMT). This "tea"
      has been used for centuries in religious and medicinal contexts in the rain
      forest areas of South America and is presently gaining the attention of
      psychedelic users in North America and Europe. OBJECTIVES: In the present study,
      the psychological effects and tolerability of ayvahuasca were assessed. METHODS:
      Three increasing doses of encapsulated freeze-dried ayahuasca (0.5, 0.75, and 1.0
      mg DMT/kg body weight) were administered to six healthy male volunteers with
      prior experience in the use of this tea, in a single-blind crossover placebo
      controlled clinical trial. RESULTS: Ayahuasca produced significant dose-dependent
      increases in five of the six subscales of the Hallucinogen Rating Scale, in the
      LSD, MBG, and A scales of the Addiction Research Center Inventory, and in the
      "liking", "good effects" and "high" visual analogue scales. Psychological effects
      were first noted after 30-60 min, peaked between 60-120 min, and were resolved by
      240 min. The tea was well tolerated from a cardiovascular point of view, with a
      trend toward increase for systolic blood pressure. Modified physical sensations
      and nausea were the most frequently reported somatic-dysphoric effects. The
      overall experience was regarded as pleasant and satisfactory by five of the six
      volunteers, while one volunteer experienced an intensely dysphoric reaction with
      transient disorientation and anxiety at the medium dose and voluntarily withdrew
      from the study. CONCLUSIONS: Ayahuasca can be described as inducing changes in
      the perceptual, affective, cognitive, and somatic spheres, with a combination of
      stimulatory and visual psychoactive effects of longer duration and milder
      intensity than those previously reported for intravenously administered DMT.

PMID- 11292013
TI  - The lens and angle-closure glaucoma.

PMID- 11292012
TI  - Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists
      from other benzodiazepines and non-benzodiazepine drugs.
AB  - RATIONALE: Triazolam is a high-efficacy benzodiazepine (BZ) agonist, which might
      be hypothesized to engender highly pharmacologically specific discriminative
      stimulus (DS) effects and distinguish among BZ agonists with different intrinsic
      efficacy. OBJECTIVES: The pharmacological specificity of the triazolam stimulus
      was determined by examining the effects of conventional and atypical BZ agonists,
      and other ligands active at the gamma-aminobutyric acidA (GABAA) receptor
      complex. Receptor mechanisms underlying the DS effects of triazolam were examined
      further using the BZ receptor antagonist flumazenil. METHODS AND RESULTS:
      Squirrel monkeys were trained to discriminate triazolam (0.03 mg/kg, i.v.) from
      vehicle under a fixed-ratio 10 (FR 10) schedule of food reinforcement. While the
      BZ agonists midazolam, diazepam, and lorazepam substituted fully for triazolam,
      chlordiazepoxide, oxazepam and nordiazepam produced only partial substitution,
      suggesting these latter compounds may have reduced intrinsic efficacy. The
      BZ/alpha1-preferring agonist zolpidem substituted fully for triazolam, and
      potencies for triazolam-like effects of BZ agonists were significantly correlated
      with potencies for their zolpidem-like effects (Rowlett et al. 1999). Flumazenil
      antagonized the DS effects of triazolam, but the slope of the Schild plot was
      significantly different from unity, suggesting multiple receptors may be involved
      in the DS effects of triazolam. CONCLUSIONS: BZ agonists can be distinguished on
      the basis of substitution for triazolam and, thus, the triazolam discrimination
      may be a useful tool for identifying compounds of different efficacy at BZ
      receptors. BZ/alpha1 receptors appear to play a prominent role in the DS effects
      of triazolam, but the contribution of other subtypes of BZ receptors cannot be
      ruled out.

PMID- 11292014
TI  - DNA-based immunotherapeutics for the treatment of allergic disease.
AB  - Allergic diseases are a growing health concern in industrialized countries.
      Despite a number of effective therapeutic options for the prevention and
      treatment of the pathophysiologic responses which characterize allergic diseases,
      the induction of true allergen desensitization remains an elusive therapeutic
      goal. Only immunotherapy (IT) has been shown to have any effect on the underlying
      hypersensitivities which mediate allergic reactions, and traditional protein
      based allergen IT has a limited scope of efficacy However, a number of reagents
      collectively termed DNA-based immunotherapeutics have proven highly effective in
      both the prevention and reversal of Th2-mediated hypersensitivity states in mouse
      models of allergic disease. Four basic DNA-based immunotherapeutic modalities
      have been used for these studies. These include immunization with gene vaccines,
      allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and
      physical allergen-ISS-ODN conjugates (AIC), as well as immunomodulation with ISS
      ODN alone. Results from many laboratories have generated guarded optimism that
      DNA-based immunotherapeutics may be effective for the reversal of allergic
      hypersensitivity states in humans, and several clinical trials have already been
      initiated. This review will focus on our present understanding of the biological
      activities of DNA-based immunotherapeutics and their application to the treatment
      of allergic diseases.

PMID- 11292015
TI  - Recombinant allergen molecules: tools to study effector cell activation.
AB  - The IgE antibody-mediated activation of allergic effector cells is the key
      pathomechanism underlying the immediate symptoms of Type I allergy, a genetically
      determined hypersensitivity disease affecting 25% of the population. In recent
      years important environmental allergens and their epitopes have become available
      as structurally defined recombinant molecules. In addition, corresponding human
      monoclonal IgE and IgG antibodies have been isolated. This review summarizes data
      obtained regarding the three-dimensional structure of allergens, their IgE
      epitopes and the recognition of allergens by IgE and IgG antibodies. In
      particular, we discuss results of recent in vitro and in vivo studies with
      defined allergen molecules, their epitopes and the corresponding antibodies which
      support the hypothesis that the density and geometrical arrangement of IgE
      epitopes on a particular allergen molecule may profoundly affect effector cell
      activation. If the structural requirements for effector cell activation can be
      delineated, it may be envisaged that, based on this knowledge, allergens can be
      converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such
      allergen derivatives may be used for allergen-specific immunotherapy with reduced
      risk of inducing anaphylactic side effects.

PMID- 11292016
TI  - Role of human FcepsilonRI+ cells in HIV-1 infection.
AB  - Enhanced serum IgE levels in adults and children with HIV-1 infection could be a
      marker of poor prognosis. HIV-1 infection is believed to involve a switch toward
      a "TH2-like" cytokine pattern. HIV-1 gp120 from different clades is a potent
      stimulus for histamine release from human basophils and mast cells. Gp120 also
      induces IL-4 and IL-13 synthesis from basophils. It functions as a viral
      superantigen by interacting with the VH3 region of IgE to induce mediator release
      from human FcepsilonRI+ cells. The chemokine receptor CCR3, which binds the
      chemokines eotaxin and RANTES, is expressed by basophils and lung mast cells. By
      interacting with the CCR3 receptor on FcepsilonRI+ cells, HIV-1 Tat protein is a
      potent chemoattractant for basophils and lung mast cells. Tat protein also
      induces IL-4 and IL-13 release from basophils. Incubation of basophils with Tat
      protein upregulates the surface expression of the CCR3 receptor, a co-receptor of
      HIV-1 infection. Extracellular Tat affects the directional migration of human
      FcepsilonRI+ cells, CCR3 expression and TH2 cytokines release. We have shown that
      HIV-1 proteins gp120 and Tat trigger the release of cytokines critical for TH2
      polarization from FcepsilonRI+ cells through two distinct mechanisms. In
      addition, Tat upregulates the beta-chemokine receptor CCR3, making FcepsilonRI+
      cells more susceptible to infection with CCR3 tropic HIV-1 isolates.

PMID- 11292017
TI  - Gastrointestinal eosinophils.
AB  - The gut-associated lymphoid tissue (GALT) is composed of lymphocytes residing in
      Peyer's patches, lamina propria, and intraepithelial compartments. In addition to
      these features which distinguish GALT from other peripheral sites of the immune
      system, the gastrointestinal immune system is also composed of resident
      eosinophils. Eosinophils are generally considered to be peripheral blood
      leukocytes that have an important pro-inflammatory role in various immune
      disorders. Although most research concerning this cell has focused on
      understanding its trafficking and function in the blood and lung, recent studies
      have also started to elucidate its regulation and function in the
      gastrointestinal tract. Interestingly, eosinophil numbers in the gastrointestinal
      tract are substantially higher than in other tissues. At baseline (healthy
      conditions), most eosinophils reside in the lamina propria in the stomach and
      intestine. Eosinophil homing to these sites occurs during embryonic development
      and their levels in perinatal mice are comparable to those in adults, indicating
      that their homing is not dependent upon the presence of intestinal flora.
      Furthermore, eosinophil localization to the lamina propria at baseline is
      critically regulated by eotaxin, a chemokine constitutively expressed throughout
      the gastrointestinal tract. Although eotaxin is required for eosinophil homing,
      its expression in the esophagus is not sufficient for eosinophil accumulation,
      since this organ is devoid of eosinophils at baseline. During Th2-associated
      inflammatory conditions (e.g. interleukin (IL)-5 overexpression or oral allergen
      challenge), marked increases of eosinophils occur not only in the lamina propria
      but also in Peyer's patches. The accumulation of Peyer's patch eosinophils, which
      mainly occurs in the outer cortex and interfollicular regions, is critically
      regulated by IL-5 and less significantly by eotaxin, suggesting the involvement
      of other eosinophil chemokines in this lymphoid compartment. Preliminary
      investigations have shown that gastrointestinal eosinophils express the
      alpha4beta7 integrin and that this molecule is responsible, in part, for
      eosinophil homing. In summary, eosinophils are resident cells of the
      gastrointestinal immune system whose levels can be induced by antigen exposure
      under Th2 conditions, in a manner that is critically regulated by eotaxin and IL
      5. We propose that eosinophils are integral members of the gastrointestinal
      immune system and are likely to be important in innate, regulatory and
      inflammatory immune responses.

PMID- 11292018
TI  - Regulation of eosinophil and neutrophil apoptosis--similarities and differences.
AB  - Apoptosis is the most common form of physiologic cell death and a necessary
      process to maintain cell numbers in multicellular organisms. In many chronic
      inflammatory diseases, reduced cell death of different types of granulocytes is
      one important mechanism for cell accumulation. Granulocytes are constantly
      produced in large amounts in the bone marrow and the same numbers die, under
      normal circumstances, within a defined time period. Changing the rate of
      apoptosis rapidly changes cell numbers in such systems. Overexpression of IL-5
      appears to be crucial for delaying eosinophil apoptosis in many allergic
      disorders, whereas overexpression of GM-CSF and G-CSF is associated with
      suppression of neutrophil apoptosis in bacterial and non-bacterial inflammations.
      Cytokine withdrawal leads to the induction of apoptosis both in vitro and in
      vivo. In contrast to the role of survival cytokines, little is known about the
      role of death factors and their receptors in the regulation of granulocyte
      apoptosis. Recent observations suggest a role for mitochondria in both eosinophil
      and neutrophil apoptosis, although the mechanisms that trigger mitochondria to
      release pro-apoptotic factors remain to be determined. Besides similarities,
      there are differences in the regulation of apoptosis between these granulocyte
      subtypes that include both expression and function of Bcl-2 and caspase family
      members. The identification of differences in the apoptosis regulation may help
      to define new molecular targets that allow specific induction of either
      eosinophil or neutrophil apoptosis by pharmacological means.

PMID- 11292019
TI  - Mast cell modulation of immune responses to bacteria.
AB  - Mast cells are key elements of the immune system. These cells release a wide
      variety of pro-inflammatory mediators which are responsible for the
      pathophysiology of many allergic diseases. Recent studies, however, have shown
      that mast cells have the capacity to modulate the host's innate immune response
      to gram negative bacteria by their ability to phagocytose bacteria, process and
      present bacterial antigens to T cells and recruit phagocytic help through the
      release of physiological amounts of pro-inflammatory mediators. Here, current
      knowledge of mast cell responses to gram negative bacteria and molecular
      mechanisms associated with mast cell bacteria interaction is reviewed.

PMID- 11292020
TI  - Eosinophil trafficking to sites of allergic inflammation.
AB  - Eosinophils play a prominent pro-inflammatory role in allergic inflammation.
      Studies utilizing flow chambers, intravital video-microscopy, and cytokine and
      adhesion molecule-deficient mice have provided important insight into the
      mechanisms of eosinophil trafficking in inflamed blood vessels and into tissues
      in vivo. While the bone marrow generation of eosinophils is finely regulated by
      interleukin (IL)-5, the trafficking of eosinophils into tissues is regulated by
      several cytokines, chemokines, and adhesion molecules with overlapping functions.
      Prospects for therapeutically inhibiting eosinophilic inflammation by inhibiting
      eosinophil adhesion to endothelium are dependent on an improved understanding of
      the relative importance of individual cytokines and adhesion molecules in
      regulating eosinophil adhesion to endothelium. Alternative strategies to inhibit
      eosinophilic inflammation include the use of immunostimulatory DNA sequences
      containing a CpG motif to act as a Th1 adjuvant to prevent Th2 responses
      associated with IL-5 and eosinophilia. Immunostimulatory DNA sequences do not
      induce eosinophil apoptosis, but function at the level of the bone marrow to
      inhibit the IL-5-induced bone marrow generation and release of eosinophils.

PMID- 11292021
TI  - Elemental signals regulating eosinophil accumulation in the lung.
AB  - In this review we identify the elemental signals that regulate eosinophil
      accumulation in the allergic lung. We show that there are two interwoven
      mechanisms for the accumulation of eosinophils in pulmonary tissues and that
      these mechanisms are linked to the development of airways hyperreactivity (AHR).
      Interleukin-(IL)-5 plays a critical role in the expansion of eosinophil pools in
      both the bone marrow and blood in response to allergen provocation of the
      airways. Secondly, IL-4 and IL-13 operate within the allergic lung to control the
      transmigration of eosinophils across the vascular bed into pulmonary tissues.
      This process exclusively promotes tissue accumulation of eosinophils. IL-13 and
      IL-4 probably act by activating eosinophil-specific adhesion pathways and by
      regulating the production of IL-5 and eotaxin in the lung compartment. IL-5 and
      eotaxin co-operate locally in pulmonary tissues to selectively and
      synergistically promote eosinophilia. Thus, IL-5 acts systemically to induce
      eosinophilia and within tissues to promote local chemotactic signals. Regulation
      of IL-5 and eotaxin levels within the lung by IL-4 and IL-13 allows Th2 cells to
      elegantly co-ordinate tissue and peripheral eosinophilia. Whilst the inhibition
      of either the IL-4/IL-13 or IL-5/eotaxin pathways resulted in the abolition of
      tissue eosinophils and AHR, only depletion of IL-5 and eotaxin concurrently
      results in marked attenuation of pulmonary inflammation. These data highlight the
      importance of targeting both IL-5 and CCR3 signalling systems for the resolution
      of inflammation and AHR associated with asthma.

PMID- 11292022
TI  - IL-5-induced airway eosinophilia--the key to asthma?
AB  - Bronchial asthma is a chronic inflammatory airway disease defined by reversible
      airway obstruction and non-specific airway hyper-responsiveness (AHR). Although
      profound insights have been made into the pathophysiology of asthma, the exact
      mechanisms inducing and regulating the disease are still not fully understood.
      Yet, it is generally accepted that the pathological changes in asthma are induced
      by a chronic inflammatory process which is characterized by infiltration of the
      bronchial mucosa with lymphocytes and eosinophils, increased mucus production and
      submucosal edema. There is increasing evidence that an imbalance in the T-helper
      (Th) cell response of genetically predisposed individuals to common environmental
      antigens plays a pivotal role in the pathogenesis of allergic bronchial asthma
      and other atopic disorders. Following allergic sensitization, T cells from atopic
      patients tend to produce elevated levels of Th2-type cytokines, especially
      interleukin (IL)-4, IL-13, IL-5 and IL-6, which induce and regulate IgE
      production and eosinophil airway infiltration. In this review, the role of Th2
      type cytokines, IgE and airway eosinophils in the induction of airway
      inflammation and AHR is discussed, and animal studies of asthma and AHR, mainly
      in rodents will be considered. A better understanding of the underlying
      mechanisms leading to asthma pathology may yield more specific immunological
      strategies for the treatment of this disease which is increasing worldwide.

PMID- 11292023
TI  - A novel human homolog of eosinophil major basic protein.
AB  - Eosinophil major basic protein (MBP) contributes to host defense and disease
      pathophysiology. Chromosome 11 contains the genes for human MBP1 (hMBP1) and a
      second novel MBP, hMBP2, in the centromere to 11q12 region. Interestingly,
      greater similarity exists between human and murine MBP1 and MBP2 orthologs,
      respectively, than between hMBP1 and hMBP2, suggesting a gene duplication event
      prior to the divergence of humans and mice. There is abundant mRNA for hMBP1 in
      both bone marrow (eosinophils and basophils) and placenta, but hMBP2 mRNA is
      present only in bone marrow (eosinophils). Comparison of proximal promoters for
      hMBP2, hMBP1, and murine MBP1 (mMBP1) shows a conserved GATA transcription factor
      binding site (functionally active in hMBP1). However, whether a C/EBP binding
      site common to hMBP1 and mMBP1 is functionally conserved in hMBP2 remains
      unresolved. Similarly, the role of conserved putative IK2 and STAT binding sites
      in MBP transcriptional control remains unknown. Like hMBP1, hMBP2 is in the
      eosinophil secondary granule. However, hMBP2 is two-fold less positively charged
      than hMBP (+8 versus +16 at neutral pH), and this difference may explain hMBP2's
      similar, but often less potent, in vitro biological activities. Overall, while
      conservation of hMBP2's amino acid sequence (63% identity with hMBP1) suggests a
      common function(s) with hMBP1, hMBP2's substantially reduced charge and the
      existence of the similar mMBP2 argue for additional, unique functions for hMBP2.

PMID- 11292024
TI  - Synaptotagmin regulates mast cell functions.
AB  - Synaptotagmin(s) (Syts), are products of a gene family implicated in the control
      of Ca2+-dependent exocytosis. Mast cells, specialized secretory cells that
      release mediators of inflammatory and allergic reactions in a process of
      regulated exocytosis, express Syt homologues and SNAREs (Soluble NSF Attachment
      proteins Receptors), which together with Syt constitute the core complex which
      mediates exocytotic vesicle docking and fusion. Rat basophilic leukemia cells
      (RBL-2H3), a tumor analogue of mucosal mast cells, express the Syt homologues Syt
      II, Syt III and Syt V Expression of Syt I, the neuronal Ca2+ sensor, in the RBL
      cells, resulted in its targeting to secretory granules and in prominent
      potentiation and acceleration of Ca2+-dependent exocytosis. Syt II is localized
      to an amine-free lysosomal compartment, which is also subjected to regulated
      exocytosis. Lysosomal exocytosis is negatively regulated by Syt II:
      overexpression of Syt II inhibited Ca2+-triggered exocytosis of lysosomes, while
      suppression of Syt II expression markedly potentiated this release. These
      findings implicate Syt homologues as key regulators of mast cell function.

PMID- 11292025
TI  - Regulation of IL-4 production in mast cells: a paradigm for cell-type-specific
      gene expression.
AB  - The role of interleukin (IL)-4 as an important immunomodulatory cytokine is well
      established. IL-4 exhibits a highly restricted pattern of expression by cells of
      distinct lineages. The cell types that produce IL-4 are located in anatomically
      distinct locations (e.g. circulating T cells vs. fixed tissue mast cells) and
      thus have access to different IL-4-responsive target cells. In addition, these
      cells appear to regulate IL-4 expression in cell-type-specific ways. These
      findings suggest that an understanding of IL-4 gene regulation in T and mast
      cells could provide the means to specifically control IL-4 release in a lineage-
      and site-specific manner. In this article we review the current knowledge
      regarding the cell-type specific regulation of IL-4 gene expression in mast cells
      and compare this to what has been defined in T cells. We show that there are
      distinct yet parallel events that control developmentally determined chromatin
      modifications, allowing accessibility of the locus, and provide the potential for
      transcription. In differentiated cells, a subset of unique cell activation
      signals initiates the cascade of events that lead to transcriptional activation
      of the IL-4 gene.

PMID- 11292026
TI  - The role of STAT6 in mast cell IL-4 production.
AB  - Interleukin (IL)-4 has an important role in regulating antibody production and
      inflammation. The major IL-4 producers are CD4+ T cells, but the development of
      an IL-4-producing phenotype in these cells requires IL-4 signaling through the
      STAT6 pathway during differentiation. The cellular source of this early IL-4 is
      not known, but mast cells are a possible candidate due to their immediate and
      indiscriminate release of IL-4 upon activation. In this review we summarize the
      evidence that STAT6 signaling is not required for mast cell IL-4 production,
      which is consistent with their possible role as a link between the innate immune
      response and T-cell activation. We also describe an isoform of STAT6 that is
      expressed in mast cells and that appears to act as a repressor of IL-4
      transcription. This STAT6 signaling pathway may be part of a feedback mechanism
      to protect surrounding tissues from IL-4-mediated inflammation during an
      infection.

PMID- 11292027
TI  - Mast cells, basophils, and eosinophils: distinct but overlapping pathways for
      recruitment.
AB  - Mast cells, basophils and eosinophils are bone marrow-derived cells that
      contribute to a variety of allergic and other immune responses. For example, they
      are relatively abundant at mucosal sites where allergic inflammation is
      occurring, and their activation and release of preformed and newly-generated
      mediators at these sites is considered central to the pathophysiology of allergic
      diseases. Given their involvement in allergic and other diseases, it is important
      to understand how these cells are selectively recruited into tissues. These cells
      share many phenotypic features, including those involved in adhesion and
      migration, yet their localization within a given tissue can be quite distinct. In
      addition, there are examples of selective recruitment of one cell type without
      the others. From studies with human cells, it is now clear that mast cells,
      basophils and eosinophils share a number of recruitment pathways with one another
      and with other cells, but that each possesses unique adhesion and migration
      responses that can contribute to their preferential accumulation. This review
      will focus on cell surface structures implicated in adhesion and migration
      responses of human mast cells, basophils and eosinophils. Both shared and
      selective expression of these molecules will be highlighted, as well as
      differences in their relative levels of expression. Cell type-specific stimuli
      that alter adhesion and migration responses will also be considered.

PMID- 11292028
TI  - Regulation of human intestinal mast cells by stem cell factor and IL-4.
AB  - Mature human mast cells are tissue-residing, key effector cells of immediate
      allergic reactions. Moreover, mast cells have been recognized as a potent
      cellular source of multiple cytokines, suggesting an important role in
      immunoregulation and host defense. Here, we report on the regulation of mature
      human mast cells isolated from intestinal tissues by stem cell factor (SCF) and
      interleukin (IL)-4. SCF is substantially necessary for mast cell survival and
      induces marginal mast cell proliferation in vitro, whereas IL-4 by itself has no
      effects on mast cell survival or proliferation. Most interestingly, in synergy
      with SCF, IL-4 strongly enhances mast cell proliferation. In the presence of SCF,
      mast cells predominantly produce pro-inflammatory cytokines including tumor
      necrosis factor (TNF)-alpha, IL-1beta, IL-6, IL-8, IL-16, and IL-18. Addition of
      IL-4 to the culture medium induces the expression of Th2-type cytokines (IL-3, IL
      5 and IL-13), and a downregulation of pro-inflammatory cytokines, namely IL-6.
      Furthermore, SCF by itself supports the predominance of the tryptase/chymase
      double-positive mast cell subtype MCTC whereas the addition of IL-4 supports the
      chymase negative MCT subtype. In conclusion, SCF may primarily regulate resident
      mast cell survival, whereas IL-4 may promote local proliferation of mast cells
      and their expression of Th2-type cytokines.

PMID- 11292029
TI  - Role of mast cells in intestinal mucosal function: studies in models of
      hypersensitivity and stress.
AB  - A single layer of epithelial cells lines the gastrointestinal tract, forming a
      critical barrier between the lunminal contents, which includes antigens and other
      noxious substances, and the body proper. It has become clear in recent years that
      the role of mast cells in the gastrointestinal mucosa is not only to react to
      antigens, but also to actively regulate the barrier and transport properties of
      the intestinal epithelium. Mucosal mast cells respond to both IgE/antigen
      dependent and non-IgE-dependent stimulation, releasing bioactive mediators into
      adjacent tissues where they induce physiological responses. Studies in models of
      hypersensitivity and stress have provided evidence that changes in mucosal
      function are due to either direct action of mast cell mediators on epithelial
      receptors and/or indirect action via nerves/neurotransmitters.

PMID- 11292030
TI  - Variable expression of activation-linked surface antigens on human mast cells in
      health and disease.
AB  - Mast cells (MC) are multipotent effector cells of the immune system. They contain
      an array of biologically active mediator substances in their granules. MC also
      express a number of functionally important cell surface antigens, including stem
      cell factor receptor (SCFR=kit=CD117), high affinity IgER (FcepsilonRI), or CSaR
      (CD88). Respective ligands can induce or promote degranulation, migration, or
      cytokine production. Other integral surface molecules can mediate adhesion or
      cell aggregation. Recent data suggest that a number of critical molecules are
      variably expressed on the surface of human MC. In fact, depending on the
      environment (organ), stage of cell maturation, type of disease, and other
      factors, MC express variable amounts of activation-linked antigens (CD25, CD63,
      CD69, CD88), cell recognition molecules (CD2, CD11, CD18, CD50, CD54), or
      cytokine receptors. At present, however, little is known about the mechanisms and
      regulation of expression of such antigens. The present article gives an overview
      of MC phenotypes in health and disease, and attempts to provide explanations for
      the phenotypic variability of MC.

PMID- 11292031
TI  - The role of Th2 cytokines in mast cell homeostasis.
AB  - Homeostatic mechanisms regulating mast cell numbers and function in peripheral
      tissues have largely focused on cytokines, such as stem cell factor, interleukin
      (IL)-3, IL-4, and IL-10, which regulate mast cell maintenance and proliferation.
      Despite these advances, little attention has been paid to the mechanisms that
      mediate mature mast cell turnover, and control of mast cell hyperplasia generated
      during Th2-mediated responses. These are important issues, as mast cells are now
      known to be multi-functional effector cells, that have the capacity to mediate
      both innate and Th2-induced immune responses. Numerous secretagogues may elicit
      mast cells to release a large number of important mediators that can cause
      chronic inflammation. Therefore, how mast cell homeostasis is regulated may have
      significant effects on normal physiology, and contribute to the genesis of
      inflammatory disease. Our laboratory has characterized an in vitro model of mast
      cell homeostasis, by which long-term exposure of murine bone-marrow-derived mast
      cells to the Th2-derived cytokines IL-3, IL-4, and IL-10, will induce
      downregulation of critical mast cell effector proteins such as Kit and Fcepsilon
      RI, followed by mast cell apoptosis. These data offer a novel role for Th2
      cytokines, acting to both initiate and resolve mast cell activation and
      proliferation. Loss of these signals may contribute to a multitude of diseases,
      such as mastocytosis and allergy

PMID- 11292032
TI  - Ribosomes and secretory granules in human mast cells: close associations
      demonstrated by staining with a chelating agent.
AB  - The distribution of ribosomes was investigated in mature human mast cells with a
      chelation-based staining protocol known to bleach DNA-rich structures, leaving
      RNA-rich structures unbleached. With this method, electron-dense ribosomes were
      adjacent to, attached to, and within secretory granules, which were also bleached
      with the chelation method that we used. The finding of these ribosome-secretory
      granule relationships suggests that secretory granules in mature human mast cells
      may participate in RNA metabolism.

PMID- 11292033
TI  - Respect [editorial].

PMID- 11292034
TI  - Tensile fixation strengths of absorbable meniscal repair devices as a function of
      hydrolysis time. An in vitro experimental study.
AB  - To determine the effect of hydrolysis time on the fixation strength of absorbable
      meniscal repair devices, adult bovine menisci were repaired with five devices and
      a suture. The ultimate tensile strength of the repair was then tested in six
      specimens immediately or after 6, 12, or 24 weeks of incubation at 37 degrees C
      in a saline solution containing antibiotics, antimycotics, and protease
      inhibitors. Immediately after implantation the Bionx Meniscus Arrow had a
      significantly higher failure strength (57.7 +/- 13.8 N) than the Linvatec
      BioStinger (35.1 +/- 6.7 N), the Innovasive Clearfix screw (34.9 +/- 13 N), the
      Surgical Dynamics S-D-sorb staple (9.4 +/- 4.6 N), and the Mitek Meniscal Repair
      System (polydioxanone) (27.2 +/- 6.0 N). However, there was no significant
      difference between the Bionx Meniscus Arrow and a 2-0 polydioxanone vertical
      suture (51.6 +/- 2.7 N). The polydioxanone-based implants demonstrated a
      significant decrease in failure strength at 12 and 24 weeks. Similarly, the
      Surgical Dynamics S-D-sorb staple lost all fixation strength by 24 weeks. The
      remaining devices showed no significant loss of failure strength over the 24-week
      period, suggesting that 24 weeks of hydrolysis does not adversely affect the
      ultimate holding power of poly L-lactide-based meniscal fixation devices.

PMID- 11292035
TI  - The association of hip strength and flexibility with the incidence of adductor
      muscle strains in professional ice hockey players.
AB  - This prospective study was conducted to determine whether hip muscle strength and
      flexibility play a role in the incidence of adductor and hip flexor strains in
      National Hockey League ice hockey team players. Hip flexion, abduction, and
      adduction strength were measured in 81 players before two consecutive seasons.
      Thirty-four players were cut, traded, or sent to the minor league before the
      beginning of the season. Injury and individual exposure data were recorded for
      the remaining 47 players. Eight players experienced 11 adductor muscle strains,
      and there were 4 hip flexor strains. Preseason hip adduction strength was 18%
      lower in the players who subsequently sustained an adductor muscle strain
      compared with that of uninjured players. Adduction strength was 95% of abduction
      strength in the uninjured players but only 78% of abduction strength in the
      injured players. Preseason hip adductor flexibility was not different between
      players who sustained adductor muscle strains and those who did not. These
      results indicate that preseason hip strength testing of professional ice hockey
      players can identify players at risk of developing adductor muscle strains. A
      player was 17 times more likely to sustain an adductor muscle strain if his
      adductor strength was less than 80% of his abductor strength.

PMID- 11292036
TI  - A biomechanical comparison of posterior cruciate ligament reconstruction
      techniques.
AB  - Most posterior cruciate ligament reconstruction techniques use both tibial and
      femoral bone tunnels for graft placement. Because of the acute angle the graft
      must make to gain entrance into the tibial tunnel, abnormal stresses are placed
      on the graft that could lead to graft failure. An alternative technique for
      posterior cruciate ligament reconstruction involves placement of the bone plug
      from the graft anatomically on the back of the tibia (inlay), preventing
      formation of an acute angle at the tibial attachment site. We used six pairs of
      human cadaver knees to compare the biomechanical properties of these two
      techniques. One knee from each pair underwent tunnel reconstruction while the
      other knee underwent inlay reconstruction. There was significantly less anterior
      posterior laxity in the inlay group when compared with the tunnel group from 30
      degrees to 90 degrees of knee flexion and after repetitive loading at 90 degrees
      of knee flexion. Evaluation of the grafts revealed evidence of mechanical
      degradation in the tunnel group but not in the inlay group. The inlay technique
      resulted in less posterior translation with less graft degradation than did the
      tunnel technique for posterior cruciate ligament reconstruction.

PMID- 11292037
TI  - The effects of extended play on professional baseball pitchers.
AB  - The purpose of this study was to investigate kinematic and kinetic changes as a
      result of extended play in baseball pitching. Seven major league baseball
      pitchers were videotaped with high-speed (120 Hz) cameras during multiple innings
      of the same game. For each athlete, two fastballs (one thrown during the initial
      inning of play and one from the final inning) were chosen for analysis. Twenty
      one physical landmarks were manually digitized from the video data. Kinematic and
      kinetic parameters were subsequently calculated relative to four phases of the
      pitching motion: windup, cocking, acceleration, and follow-through. Paired t
      tests revealed that seven parameters changed significantly between early and late
      innings. These included decreases in maximum external rotation of the shoulder,
      knee angle at ball release, ball velocity, maximum distraction force at both the
      shoulder and elbow, and horizontal adduction torque at both release and its
      maximum value. Ultimately, a decline in performance was evident by a 2 m/s (5
      mph) drop in ball speed. It is unclear whether the kinematic and kinetic changes
      occurred because of fatigue or if protective mechanisms were adopted.

PMID- 11292038
TI  - Instrumented measurement of glenohumeral joint laxity and its relationship to
      passive range of motion and generalized joint laxity.
AB  - The purpose of this study was to objectively characterize in vivo glenohumeral
      joint laxity using an instrumented shoulder arthrometer. Secondary objectives
      were to examine the relationship of glenohumeral joint laxity with passive range
      of motion and generalized joint laxity. Fifty-one recreational athletes with no
      history of shoulder injury or long-term participation in overhead sports
      participated in this study. Anterior and posterior laxity data were obtained at
      displacement forces of 67, 89, 111, and 134 N. Bilateral passive shoulder range
      of motion measures were obtained, and a modified Beighton Mobility Score was used
      to quantify generalized joint laxity. There were no significant differences in
      glenohumeral joint laxity between the right and left shoulders (P values = 0.14
      to 0.73). No significant differences in laxity were seen between directions
      (F(1,400) = 1.35, P = 0.25). However, significant differences were observed
      between force levels (F(3,400) = 27.17, P < 0.0001). No moderate or stronger
      correlations between laxity, passive range of motion, and generalized joint
      laxity were seen. These data confirm the presence of a wide spectrum of symmetric
      laxity in subjects that fails to correlate strongly with passive range of motion
      or generalized joint laxity.

PMID- 11292039
TI  - Radiographic joint space narrowing and histologic changes in a rabbit
      meniscectomy model of early knee osteoarthrosis.
AB  - The purpose of this study was to compare weightbearing radiographs with
      histologic cartilage evaluation in a rabbit meniscectomy model of the early stage
      of osteoarthrosis. Fifteen rabbits had a medial meniscectomy performed in one
      knee and a sham operation in the other knee. Five rabbits each were sacrificed at
      13, 25, and 40 weeks after surgery. Radiographic joint space width and histologic
      cartilage changes of the medial knee compartment were quantified. Five non
      operated knees and five knees in which the meniscus had been removed immediately
      before the evaluations served as control specimens. Overall, the joint space of
      the peripheral part of the medial knee compartment was narrower in knees operated
      on for meniscus removal than in sham-operated knees (P < 0.003). In the knees
      with the meniscus removed, more cartilage changes were seen at the joint surface
      area of contact on radiographs than in the sham-operated knees (P < 0.0015).
      Indeed, the area of contact had cartilage changes similar to those in the whole
      medial compartment. However, there was no correlation between the degree of
      histologic cartilage change and the corresponding joint space measurements. Joint
      space width as measured on weightbearing radiographs is reduced after
      meniscectomy in the rabbit, but it does not reflect the degree of cartilage
      damage of the loaded joint surfaces in early stages of osteoarthrosis.

PMID- 11292040
TI  - The elongation behavior of the anterior cruciate ligament graft in vivo. A long
      term follow-up study.
AB  - The relationship between the elongation values of an autogenous bone-patellar
      tendon-bone graft immediately after fixation and the anterior-posterior laxity of
      the knee 5 years later was studied in vivo. Immediately after fixation, the
      change in the graft midsubstance length during passive knee flexion-extension was
      measured using a Hall-effect transducer, and anterior-posterior knee laxity was
      measured with the KT-1000 arthrometer. Subjects were divided into group 1 (N =
      6), with graft elongation values bounded by the 95% confidence intervals of the
      normal anterior cruciate ligament elongation values, and group 2 (N = 7),
      subjects with values outside these intervals. Immediately after reconstruction,
      the side-to-side difference in anterior-posterior laxity between the
      reconstructed and uninjured knees was not different between group 1 (-2.6 +/- 0.7
      mm, mean +/- SEM) and group 2 (-1.7 +/- 1.0 mm) (P = 0.49). At 5-year follow-up,
      the difference was 1.2 +/- 0.7 mm for group 1, while for group 2 it was
      significantly greater at 4.7 +/- 0.6 mm (P = 0.004). At surgery, graft elongation
      values produced by flexion of the knee that are outside the limits of the
      anterior cruciate ligament result in significant increases in anterior knee
      laxity at long-term follow-up, while grafts with elongation values similar to the
      normal anterior cruciate ligament do not. Not only is restoration of anterior
      posterior laxity values to within normal limits important, but the biomechanical
      behavior of the graft produced by flexion-extension of the knee should be
      appreciated.

PMID- 11292041
TI  - Open and closed kinetic chain exercises in the early period after anterior
      cruciate ligament reconstruction. Improvements in level walking, stair ascent,
      and stair descent.
AB  - Thirty-seven patients who had undergone anterior cruciate ligament reconstruction
      were tested in a gait analysis laboratory at 2 and 6 weeks after surgery. Between
      test sessions, patients were randomly assigned to a course of either closed or
      open kinetic chain resistance exercises (3 sessions per week for 4 weeks). Gait
      analysis consisted of bilateral calculations of knee joint angle, moment, and
      power during level walking, stair ascent, and stair descent. An analysis of
      variance on the effects of training group and test session indicated that the
      only variable to be significantly affected by the type of exercise program was
      the amount of knee flexion at the beginning of step-up (P < 0.05). All other
      measures of knee angle, moment, and power (16 total variables) showed no
      significant difference between the exercise groups. All variables measured on the
      injured side showed significant improvement from test 1 to test 2 (P < 0.05), but
      the injured leg remained functionally deficient when compared with the uninjured
      leg. These data suggest that there are no clinically significant differences in
      the functional improvement resulting from the choice of open or closed kinetic
      chain exercises in the early period after this surgery.

PMID- 11292042
TI  - Tissue-engineered rotator cuff tendon using porcine small intestine submucosa.
      Histologic and mechanical evaluation in dogs.
AB  - To determine its efficacy in stimulating the regeneration of a rotator cuff
      tendon, an implant of 10-ply porcine small intestinal submucosa was used to
      replace a completely resected infraspinatus tendon in 21 adult mongrel dogs. The
      contralateral infraspinatus tendon was elevated and then reattached to the
      greater tubercle with sutures to mimic conventional repair (sham operation).
      Mechanical evaluations were performed at 0, 3, and 6 months (five specimens at
      each time period). Histologic comparisons were made at 3 and 6 months (three
      specimens). At both times, the gross appearance, histologic continuity, and
      failure mode of the constructs mimicked those of sham-operated and native
      infraspinatus tendons, thus suggesting host tissue ingrowth and implant
      remodeling with solid integration of the regenerated tissue to muscular and bony
      interfaces. Tissue ingrowth occurred without histologic evidence of foreign body
      or immune-mediated reactions or adhesions to peripheral tissues. Sham operations
      simulated tendon mobilization and reimplantation procedures routinely performed
      to treat chronic rotator cuff tendon injuries. Although the ultimate strength of
      small intestinal submucosa-regenerated tendons was significantly less than that
      of native infraspinatus tendons (P < 0.001), it was similar to that of
      reimplanted tendons at 3 (P > 0.05) and 6 months (P > 0.05).

PMID- 11292043
TI  - Endoscopic calcaneoplasty.
AB  - Endoscopic calcaneoplasty offers access to the retrocalcaneal space, thereby
      making it possible to remove inflamed retrocalcaneal bursa as well as the
      posterosuperior part of the calcaneus in applicable cases of painful hindfoot. In
      this study, endoscopic calcaneoplasty was performed in 21 procedures in 20
      patients. All of the patients had typical complaints of inflammation of the
      retrocalcaneal bursa that were unresponsive to nonoperative treatment for more
      than 6 months. In all patients a superior calcaneal angle of more than 75 degrees
      and positive parallel pitch lines were present on the lateral calcaneal
      radiograph. The mean follow-up was 3.9 years (range, 2 to 6.5). There were no
      surgical complications and no postoperative infections. One patient had a fair
      result, 4 patients had good results, and the remaining 15 patients had excellent
      results. Whether this operation is performed by endoscopic or open technique,
      enough bone must be removed to prevent impingement of the bursa between the
      calcaneus and Achilles tendon. Endoscopic calcaneoplasty is a minimally invasive
      technique performed in an outpatient setting and combined with a functional
      rehabilitation program. The procedure has low morbidity. Patients have a short
      recovery time and quickly resume work and sports.

PMID- 11292044
TI  - Intrinsic risk factors for the development of patellar tendinitis in an athletic
      population. A two-year prospective study.
AB  - Retrospective studies have suggested various factors that might cause a
      disposition to develop patellar tendinitis, but no prospective data exist to
      determine any relationships. The purpose of this study was to determine the
      intrinsic risk factors for the development of patellar tendinitis in an athletic
      population. Before the study, 138 male and female students of physical education
      were evaluated for anthropometric variables, leg alignment characteristics, and
      muscle tightness and strength parameters. During the 2-year study, 19 of the 138
      students developed patellar tendinitis. In all cases the diagnosis was confirmed
      by the presence of a hypoechogenic nodular lesion in the proximal region of the
      patellar tendon. Univariate and stepwise discriminant function analyses were
      performed comparing the various measurements. These analyses revealed that the
      only significant determining factor was muscular flexibility, with the patellar
      tendinitis patients being less flexible in the quadriceps and hamstring muscles
      (P < 0.05). The results of this study demonstrate that lower flexibility of the
      quadriceps and hamstring muscles may contribute to the development of patellar
      tendinitis in an athletic population. Therefore, the prevention of this condition
      in athletes should be focused on screening for and treating poor quadriceps and
      hamstring muscle flexibility.

PMID- 11292045
TI  - Intrinsic and extrinsic risk factors for anterior cruciate ligament injury in
      Australian footballers.
AB  - The aim of this study was to examine the interaction between intrinsic (player
      related) and extrinsic (environment-related) variables as risk factors for
      anterior cruciate ligament injury in Australian football. Between 1992 and 1999,
      100,820 player-match exposures were analyzed for risk of anterior cruciate
      ligament injury using logistic regression analysis. There were 63 surgically
      proven noncontact anterior cruciate ligament injuries. The strongest risk factors
      were a player history of anterior cruciate ligament reconstruction either in the
      previous 12 months (relative risk [RR], 11.33; 95% confidence interval [CI], 4.02
      to 31.91) or before the previous 12 months (RR, 4.44; 95% CI, 2.46 to 8.01).
      Weather conditions that were associated with dry field conditions--high water
      evaporation in the month before the match (RR, 2.55; 95% CI, 1.44 to 4.52) and
      low rainfall in the year before the match (RR, 2.87; 95% CI, 1.30 to 6.32)--were
      also significantly associated with these injuries. The increased risk of injury
      in the first 12 months after reconstruction was associated with the reconstructed
      knee, whereas after 12 months there was an even distribution of new injuries to
      the reconstructed knee and contralateral knee. A history of anterior cruciate
      ligament reconstruction is a risk factor for further injury. Weather conditions
      of high evaporation and low rainfall before matches are associated with
      noncontact anterior cruciate ligament injury.

PMID- 11292046
TI  - Biomechanical and topographic considerations for autologous osteochondral
      grafting in the knee.
AB  - This study characterizes the donor and recipient sites involved in osteochondral
      autograft surgery of the knee with respect to articular cartilage contact
      pressure, articular surface curvature, and cartilage thickness. Five cadaveric
      knees were tested in an open chain activity simulation and kinematic data were
      obtained at incremental knee flexion angles from 0 degrees to 110 degrees.
      Surface curvature, cartilage thickness, and contact pressure were determined
      using a stereophotogrammetry method. In all knees, the medial trochlea,
      intercondylar notch, and lateral trochlea demonstrated nonloadbearing regions.
      Donor sites from the distal-medial trochlea were totally nonloadbeadng. For the
      intercondylar notch, lateral trochlea, and proximal-medial trochlea, however, the
      nonloadbearing areas were small, and typical donor sites in these areas partially
      encroached into adjacent loadbearing areas. The lateral trochlea (77.1 m(-1)) was
      more highly curved than the typical recipient sites of the central trochlea (23.3
      m(-1)), medial femoral condyle (46.8 m(-1)), and lateral femoral condyles (42.9
      m(-1)) (P < 0.05). Overall, the donor sites had similar cartilage thickness
      (average, 2.1 mm) when compared with the typical recipient sites (average, 2.5
      mm). The lateral trochlea and medial trochlea curvatures were found to better
      match the recipient sites on the femoral condyles, while the intercondylar notch
      better matched the recipient sites of the central trochlea. The distal-medial
      trochlea was found to have the advantage of being nonloadbearing. Preoperative
      planning using the data presented will assist in more conforming, congruent
      grafts, thereby maximizing biomechanical function.

PMID- 11292047
TI  - Topographic matching of selected donor and recipient sites for osteochondral
      autografting of the articular surface of the femoral condyles.
AB  - The purpose of this study was to define the topography of the articular surface
      of the femoral condyles and to develop a method for computerized topographic
      matching of donor and recipient sites for osteochondral transplantation. The
      condyles of seven fresh cadaveric femurs were mounted on the rotating stage of a
      laser-based coordinate measuring machine. An anatomic coordinate system defining
      the articular surface of the condyles was created. Customized software was
      developed to allow selection and topographic matching of osteochondral graft
      donor and recipient sites from any location on the surface of the condyles. For
      cartilage defects within the weightbearing portions of the medial or lateral
      femoral condyles, grafts taken from sites from the most medial or lateral
      portions of the patellar groove provided a significantly better topographic match
      than did grafts taken from the central intercondylar notch.

PMID- 11292048
TI  - Development and evaluation of an activity rating scale for disorders of the knee.
AB  - Reports of clinical studies of patients with knee disorders should routinely
      include their activity levels to enable comparison of treatment groups and to
      allow generalizability. The goal of this study was to develop and evaluate a new
      rating scale to measure activity levels of patients. We assessed reliability by
      administering the scale to 40 subjects on 2 separate occasions, 1 week apart.
      Validity was evaluated by comparing the activity rating on the new scale with
      that from other instruments that use activity level scales (concurrent construct
      validity) and also by correlating the score on the new scale with age (divergent
      validity). Patients easily understood the scale and were able to complete it in 1
      minute. The reliability was high (intraclass correlation coefficient, 0.97). The
      scale also correlated well with existing activity rating scales: Spearman
      correlation coefficient for Cincinnati score, 0.67; for Tegner scale, 0.66; for
      Daniel scale, 0.52. The activity score was significantly inversely correlated
      with age (P = 0.002), indicating divergent validity. This instrument will
      facilitate generalizability of results and allow more accurate comparisons among
      patient groups in outcomes research in sports medicine.

PMID- 11292049
TI  - Inversion and eversion strengths in the weightbearing ankle of young women.
      Effects of plantar flexion and basketball shoe height.
AB  - Maximum isometric ankle inversion and eversion muscle strengths were measured
      under full unipedal weightbearing in 20 healthy young adult women. When the women
      wore a low-top shoe, the mean (standard deviation) maximum external eversion
      moments resisted with the foot in 0 degrees and 32 degrees of ankle plantar
      flexion were 24.1 (7.6) and 24.1 (8.1) N x m, respectively, while the
      corresponding values for maximum inversion moments resisted were 14.7 (6.8) and
      17.4 (6.4) N x m, respectively. Both shoe height and ankle plantar flexion
      affected the overall inversion moment resisted by 17% (P = 0.03) at 0 degrees of
      ankle plantar flexion to 11.9% (P = 0.003) at 32 degrees of ankle plantar
      flexion. However, neither shoe height nor ankle plantar flexion significantly
      affected the maximum eversion moment resisted. Although eversion muscle strength
      of the young women averaged 39% less than the corresponding value found in young
      men, the sex difference was not significant when ankle strengths were normalized
      by body size (body weight x height). Thus, when data from healthy young men and
      women were averaged, eversion and inversion strengths averaged 1.6% and 2.7%,
      respectively, of body weight x height.

PMID- 11292050
TI  - The biomechanical interdependence between the anterior cruciate ligament
      replacement graft and the medial meniscus.
AB  - To establish a quantitative biomechanical relationship between the anterior
      cruciate ligament graft and the medial meniscus, 10 human cadaveric knees were
      examined using the robotic/universal force-moment sensor testing system. In
      response to a combined 134-N anterior and 200-N axial compressive tibial load,
      the resulting kinematics of the knee and the in situ forces in the anterior
      cruciate ligament, the anterior cruciate ligament graft, and the medial meniscus
      were measured. Anterior tibial translation significantly increased after anterior
      cruciate ligament transection, between 6.8 +/- 2.3 mm at full extension and 12.6
      +/- 3.3 mm at 30 degrees of flexion. Consequently, the resultant forces on the
      medial meniscus, ranging from 52 +/- 30 N to 63 +/- 51 N between full extension
      and 90 degrees of knee flexion in the intact knee, were doubled as a result of
      anterior cruciate ligament deficiency. However, after anterior cruciate ligament
      reconstruction, anterior tibial translations were restored to the levels of the
      intact knee, and thus the forces on the medial meniscus were restored as well.
      Likewise, the in situ forces in the anterior cruciate ligament replacement graft
      increased between 33% and 50% after medial meniscectomy.

PMID- 11292051
TI  - Acute transverse patellar fracture associated with weightlifting. Case report and
      literature review.

PMID- 11292052
TI  - Salvage of failed acromioclavicular joint reconstruction using autogenous
      semitendinosus tendon from the knee. Surgical technique and case report.

PMID- 11292053
TI  - Intraneural ganglion cyst of the peroneal nerve accompanied by complete foot
      drop. A case report.

PMID- 11292054
TI  - Closed reduction and immobilization for traumatic isolated dislocation of the
      carpometacarpal joint of the thumb in rugby football players. Two case reports.

PMID- 11292055
TI  - Meniscal allografts--where do we stand?
AB  - Meniscal transplantation has been recommended for selected meniscus-deficient
      patients in an effort to forestall progressive joint degeneration. Meniscal
      allograft transplantation may be considered for patients with symptoms (pain and
      swelling) due to meniscal deficiency in an effort to prevent progressive
      articular cartilage degeneration. Medial meniscal transplantation may also be
      considered during concomitant anterior cruciate ligament reconstruction, since
      absence of the medial meniscus results in increased forces in the anterior
      cruciate ligament graft. Contraindications for meniscal transplantation include
      advanced articular cartilage degeneration (especially on the flexion
      weightbearing zone of the condyle), axial malalignment, and flattening of the
      femoral condyle. Patient evaluation should include standing, long-leg radiographs
      for assessment of the mechanical axis and magnetic resonance imaging with
      appropriate pulse sequences for evaluation of hyaline cartilage thickness. Fresh
      frozen and cryopreserved allografts are currently the most commonly used
      transplantation materials. Appropriate graft sizing is critical; most tissue
      banks size the meniscus based on radiographic tibial plateau measurements. Early
      results of meniscal transplantation indicate predictable improvements in pain,
      swelling, and knee function; however, no long-term results are available. Poor
      results have been reported in patients with advanced cartilage degeneration.
      Objective evaluations often demonstrate some degree of degeneration of the
      posterior horn of the transplant. Earlier transplantation should be considered
      for patients with known meniscal deficiency.

PMID- 11292056
TI  - The effect of ciprofloxacin on tendon, paratenon, and capsular fibroblast
      metabolism.

PMID- 11292057
TI  - Radiofrequency energy-induced heating of bovine articular cartilage using a
      bipolar radiofrequency electrode.

PMID- 11292058
TI  - Graft fixation in cruciate ligament reconstruction.

PMID- 11292059
TI  - Biocompatibility of intraocular lenses.

PMID- 11292060
TI  - NMDA and glycine regulate the affinity of the Mg2+-block site in NR1-1a/NR2A NMDA
      receptor channels expressed in Xenopus oocytes.
AB  - NMDA receptors are glutamate-regulated ion channels of critical importance for
      many neurophysiological and neuropathological processes. Mg2+ blocks the NMDA
      receptor by binding to the channel pore with an apparent affinity that depends on
      the membrane potential. We have investigated the effect of NMDA and the required
      co-agonist glycine on the affinity of the Mg2+ block site in NR1-1a/NR2A NMDA
      receptors expressed in Xenopus oocytes. We found that NMDA and glycine increase
      the IC50 value of the Mg2+-block site at pH 7.4 and in the presence of
      physiological concentration of Ca2+. The increase the IC50 value may correspond
      to a decrease in Mg2+-block affinity. This effect may result in an increased
      influx of Ca2+, and this influx may constitute up to a third of the total Ca2+
      influx induced by NMDA. At high pH, or at low concentrations of Ca2+, NMDA and
      glycine have an opposite effect and instead decreased the IC50 value of the Mg2+
      block. These results indicate that glutamate and glycine can regulate the
      affinity of the Mg2+-block site. This effect may have implications for the
      understanding the role of NMDA receptors both under physiological and
      pathophysiological conditions.

PMID- 11292061
TI  - Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1
      messenger RNA by a combination of mono-unsaturated fatty acid and insulin in
      hepG2 cells.
AB  - The effects of bezafibrate (PPAR alpha activator) and troglitazone (PPAR gamma
      activator) on the expression of plasminogen activator inhibitor type-1 (PAI-1) in
      HepG2 cells were investigated. Exposure of the cells for 24 hours to either oleic
      acid or insulin showed no obvious effects on PAI-1 synthesis, whereas the
      combination of the two agents induced a 2.3-fold increase in PAI-1 synthesis,
      which was accompanied by a 3-fold increase in both the 2.2 kb and 3.2 kb forms of
      PAI-1 mRNA. This up-regulation of PAI-1 synthesis was attenuated by bezafibrate
      in a dose-dependent manner (1-100 microM) with 30% reversal at 100 microM. In
      contrast, troglitazone further stimulated PAI-1 synthesis to 140% of the level
      obtained in the presence of both oleic acid and insulin. This attenuation by
      bezafibrate and enhancement by troglitazone required the presence of both oleic
      acid and insulin. It is interesting that PAI-1 expression was affected so
      differently by these two PPAR activators.

PMID- 11292062
TI  - Design, synthesis, and characterization of a novel, 4-[2-(diphenylmethoxy)ethyl]
      1-benzyl piperidine-based, dopamine transporter photoaffinity label.
AB  - The dopamine transporter (DAT) has been implicated strongly in cocaine's
      reinforcing effects. Many derivatives of piperidine analogs of GBR 12909 have
      been developed and were found to be quite potent and selective for the DAT. In
      this regard, most of these derivatives were found to be much more selective for
      the DAT than conventional GBR compounds e.g. GBR 12909 when their selectivity was
      compared with the serotonin transporter (SERT). A brief structure-activity
      relationship (SAR) study has been carried out in the development of a novel
      photoaffinity ligand which illustrated the effect of the presence of a sterically
      bulky iodine atom next to the azido group in activity and selectivity for the
      DAT. This SAR study also led to the development of the compound 4 which is one of
      the most potent and selective blockers for the DAT known today. The photoaffinity
      ligand [125I]AD-96-129 was incorporated into the DAT molecule as was demonstrated
      by immunoprecipitation with serum 16 which is specific for DAT. This
      photolabeling was antagonized by DAT-specific blockers and was unaffected by
      specific SERT and norepinephrine transporter (NET) blockers indicating
      interaction of this novel ligand with the DAT.

PMID- 11292063
TI  - Differential inhibition of progesterone synthesis in bovine luteal cells by
      estrogens and androgens.
AB  - We investigated the roles of estrogens and androgens in the progesterone
      biosynthesis of bovine luteal cells. The responsiveness of primary luteal cells
      to the stimulation of tropic agents was observed in a dose-dependent manner.
      Estrogens and androgens significantly inhibited tropic agent-induced progesterone
      secretions, but glucocorticoids did not, which indicated the inhibitions were
      specific. The failure of exogenous 8-Br-cAMP to prevent these inhibitions
      suggested that took place at the post-cAMP steps. The immunoblot showed that
      testosterone remarkably decreased the amount of induced P450scc protein after 6
      hour treatment, yet 17beta-estradiol did not. The 3beta-HSD activity assays
      demonstrated that both 17beta-estradiol and testosterone efficiently blocked
      induced 3beta-HSD activities. Both inhibitory effects of E2 and T on progesterone
      synthesis were observed one hour after treatment and accompanied with suppressed
      3beta-HSD activities. This study presents that estrogens and androgens
      specifically inhibit bovine luteal function through different mechanisms.

PMID- 11292064
TI  - Toxic effect of troglitazone on cultured rat hepatocytes.
AB  - We examined the cytotoxicity of troglitazone toward cultured rat hepatocytes. The
      drug concentration- and time-dependently decreased cell viability and increased
      lactate dehydrogenase leakage from the cells. Troglitazone-induced cell death was
      characterized by "DNA ladders", condensation of nuclei, and a positive reaction
      to in situ nick-end labeling. The results indicate that troglitazone can cause
      apoptotic cell death in cultured rat hepatocytes.

PMID- 11292066
TI  - Inverse relationship between plasma epinephrine and testosterone levels during
      acute glucoprivation in healthy men.
AB  - In healthy men, a decrease in plasma testosterone levels was observed in the
      context of metabolic stress. While physiological mechanisms underlying this
      response are unclear, there are several lines of evidence suggesting circulating
      epinephrine's influence on plasma testosterone levels. The purpose of this study
      was to directly relate stress-induced changes in plasma testosterone and
      epinephrine. The stressor used was blockade of glucose metabolism with
      pharmacological doses (40 mg/kg) of 2 deoxyglucose (2DG). Arterial plasma samples
      from 10 healthy males were assayed at 20 minutes intervals for 60 minutes for the
      concentrations of testosterone, epinephrine and related biochemicals. Bolus
      administration of 2DG resulted in progressive decline in testosterone and
      increases in epinephrine and norepinephrine plasma levels (mean change from
      baseline: 29, 2530 and 186%, respectively). Inverse correlation was detected
      between both absolute (r(s)=-0.72; df=8; p=0.017) and baseline-corrected
      testosterone concentrations at the 60 minute time point and epinephrine area
      under the curve values. Our results suggest that adrenomedullary activation may
      be involved in stress-induced testosterone effects. The implications of these
      data for the understanding of the role of catecholamines in glucoprivic stress
      response are discussed.

PMID- 11292065
TI  - Expression of thioredoxin in bleomycin-injured airway epithelium: possible role
      of protection against bleomycin induced epithelial injury.
AB  - Bleomycin (BLM) is an anticancer drug, administration of which leads to severe
      lung injury, in which the generation of intracellular reactive oxygen species
      (ROS) is thought to participate in that. Thioredoxin (TRX) has been found to
      function as a powerful antioxidant by reducing ROS, and thus protecting against
      ROS-mediated cytotoxicity. However, a protective role of TRX in BLM-induced lung
      injury has not been determined. In the present study, we therefore attempted to
      clarify this issue. Human TRX-transfected L929 murine fibrosarcoma cells were
      more resistant to BLM-induced cytotoxicity than the parental and the control
      transfected cells, indicating that TRX plays the protective role in BLM-induced
      cytotoxicity. Next, we examined TRX expression in the lung of in vivo model of
      BLM-induced lung injury and BLM-stimulated bronchial epithelial cells in vitro to
      clarify the role of TRX in BLM-induced lung injury. In the lungs of BLM-treated
      mice, the expression of TRX was strongly induced in bronchial epithelial cells.
      TRX expression was also up-regulated at both the mRNA and protein levels in
      cultured BEC with the treatment with BLM. However, the expression of other major
      antioxidants, such as Cu/Zn-SOD, Mn-SOD, catalase and glutathione peroxidase, was
      not affected by BLM. These observations suggest that the cellular reduction and
      oxidation (redox) state modified by TRX is involved in the BLM resistancy and the
      induction of TRX in bronchial epithelial cells might play a protective role in
      BLM-induced lung injury.

PMID- 11292067
TI  - Aging and gender affect the response of thyrotropin (TSH) to gastrin releasing
      peptide (GRP) in rats.
AB  - We had previously shown that GRP acts directly at the pituitary gland inhibiting
      basal and TRH-stimulated TSH secretion in adult male rats. In this study we
      showed a gender dimorphism in this response of old animals pituitaries to GRP. In
      both female and male young adult animals, GRP-incubated pituitaries showed
      approximately 50% less basal and TRH-stimulated TSH secretion to the medium,
      without affecting the pituitary content of TSH. However, GRP did not have any
      significant effect upon TSH secretion in old male rats, but the old female showed
      the same degree of response to GRP as the young adult female rat, regarding basal
      and TRH-stimulated TSH secretion, while the TSH pituitary content after GRP
      incubation was higher than that of the young female group. Our data suggest a
      loss of thyrotrope responsiveness to GRP in aged male rats that could contribute
      to the decrease in TSH pituitary stores leading to lower basal and TRH-stimulated
      TSH secretion. Meanwhile, the preservation of GRP responsiveness could help in
      the relative maintenance of these parameters in the old female rat.

PMID- 11292068
TI  - Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole,
      bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine,
      cimetidine and misoprostol in mice.
AB  - The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a
      longly described suitable counterpart of dopamine blocker cysteamine-duodenal
      lesion. In this, the contribution of blockade of central/peripheral dopamine
      receptors and prostaglandins synthesis, along with influence of antiulcer agents
      was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after
      haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline)
      (i) or in combination (ii,iii)). Supporting central dopamine predominance for
      haloperidol stomach lesion induction, co-administration of peripheral dopamine
      receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii),
      or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+
      indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline
      challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a
      gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal,
      M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine
      (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg),
      pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole
      (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and
      ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral
      blockade influence: in haloperidol+domperidone mice, previously effective
      bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not
      attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in
      haloperidol+indomethacin mice, previously effective agents, bromocriptine or
      omeprazole were not active, while BPC 157 effect was only lessened.

PMID- 11292069
TI  - Asafoetida inhibits early events of carcinogenesis: a chemopreventive study.
AB  - Ferula (a genus of many species) commonly known as asafoetida is used as a
      flavoring agent in food and is used as a traditional medicine for many diseases
      in many parts of world. In the current investigation, we report the antioxidant
      and anticarcinogenic potential of asafoetida (Ferula narthex) in swiss albino
      mice. A single dose of TPA (20 nmol/0.2 ml acetone/animal), a known tumor
      promoter decreased the cellular antioxidant level significantly (p<0.01) when
      applied topically to mice skin. It also induced the ODC activity, rate of DNA
      synthesis, hydrogen peroxide level, xanthine oxidase activity and protein
      carbonyl content in mice skin significantly (p<0.01). These events are early
      biomarkers of carcinogenesis. However, the pretreatment of animals with
      asafoetida (300, 400 and 500 microg/200 microl acetone/animal) caused the
      reversal of all events significantly (p<0.01). The pretreament of animals with
      asafoetida recovered the antioxidant level and reversed the induced ODC activity
      and DNA synthesis significantly (p<0.01). We conclude that asafoetida is a potent
      antioxidant and can afford protection against free radical mediated diseases such
      as carcinogenesis.

PMID- 11292070
TI  - Indomethacin prevents the induction of inducible nitric oxide synthase in murine
      peritoneal macrophages and decreases their nitric oxide production.
AB  - Indomethacin (0.14-.5 mM concentration) inhibits nitric oxide production in
      murine peritoneal macrophages. This was evidenced by measuring both nitrite
      production or 14C-L-citrulline formation. The inhibition was caused by the
      diminution of de novo inducible nitric oxide synthase production as demonstrated
      by Western blotting experiment. The effect of indomethacin after 4 h treatment
      was irreversible. NO synthase and arginase activities and the uptake of arginine
      were not directly affected by the drug. Indomethacin also decreased uridine
      incorporation in macrophages. The effect of indomethacin on the induction of
      other enzymes (i.e. arginase) was weaker.

PMID- 11292071
TI  - Inhibition of Shiga toxin-induced tumor necrosis factor-alpha production and gene
      expression in human monocytic cells by CV6209.
AB  - Cytokines, in particular TNF-alpha, appear to be necessary to develop the
      pathological process of Shiga toxin-producing Escherichia coli (STEC) infection.
      In this study, we investigated whether CV6209, a PAF antagonist, could modulate
      Shiga toxin (Stx)-induced TNF-alpha production in human monocytic cells. Cells
      were stimulated by Stx1 or Stx2 (5 ng/ml) with or without CV6209 addition (12-100
      microg/ml) for various periods of time. CV6209 significantly suppressed Stx
      induced TNF-alpha production in a dose- and time-dependent manner. Reverse
      transcription-polymerase chain reaction (RT-PCR) analysis showed that CV6209
      suppressed Stx-mediated TNF-alpha mRNA expression. Our results indicated that
      CV6209 had an important regulatory effect on Stx-induced TNF-alpha production and
      gene expression.

PMID- 11292072
TI  - Sugar-dependent alterations in cotyledon and leaf development in transgenic
      plants expressing the HDZhdip gene ATHB13.
AB  - ATHB13 is a new member of the homeodomain leucine zipper (HDZip) transcription
      factor family of Arabidopsis thaliana. Constitutive high-level expression of the
      ATHB13 cDNA in transgenic plants results in altered development of cotyledons and
      leaves, specifically in plants grown on media containing metabolizable sugars.
      Cotyledons and leaves of sugar-grown transgenic plants are more narrow and the
      junction between the petiole and the leaf blade less distinct, as compared to the
      wild type. High-level expression of ATHB13 affects cotyledon shape by inhibiting
      lateral expansion of epidermal cells in sugar-treated seedlings. Experiments with
      non-metabolizable sugars indicate that the alteration in leaf shape in the ATHB13
      transgenics is mediated by sucrose sensing. ATHB13 further affects a subset of
      the gene expression responses of the wild-type plant to sugars. The expression of
      genes encoding beta-amylase and vegetative storage protein is induced to higher
      levels in response to sucrose in the transgenic plants as compared to the wild
      type. The expression of other sugar-regulated genes examined is unaffected by
      ATHB13. These data suggest that ATHB13 may be a component of the sucrose
      signalling pathway, active close to the targets of the signal transduction.

PMID- 11292073
TI  - Stress-induced accumulation and tissue-specific localization of dehydrins in
      Arabidopsis thaliana.
AB  - Stress-induced accumulation of five (COR47, LTI29, ERD14, LTI30 and RAB18) and
      tissue localization of four (LTI29, ERD14, LTI30 and RAB18) dehydrins in
      Arabidopsis were characterized immunologically with protein-specific antibodies.
      The five dehydrins exhibited clear differences in their accumulation patterns in
      response to low temperature, ABA and salinity. ERD14 accumulated in unstressed
      plants, although the protein level was up-regulated by ABA, salinity and low
      temperature. LTI29 mainly accumulated in response to low temperature, but was
      also found in ABA- and salt-treated plants. LTI30 and COR47 accumulated primarily
      in response to low temperature, whereas RAB18 was only found in ABA-treated
      plants and was the only dehydrin in this study that accumulated in dry seeds.
      Immunohistochemical localization of LTI29, ERD14 and RAB18 demonstrated tissue
      and cell type specificity in unstressed plants. ERD14 was present in the vascular
      tissue and bordering parenchymal cells, LTI29 and ERD14 accumulated in the root
      tip, and RAB18 was localized to stomatal guard cells. LTI30 was not detected in
      unstressed plants. The localization of LTI29, ERD14 and RAB18 in stress-treated
      plants was not restricted to certain tissues or cell types. Instead these
      proteins accumulated in most cells, although cells within and surrounding the
      vascular tissue showed more intense staining. LTI30 accumulated primarily in
      vascular tissue and anthers of cold-treated plants. This study supports a
      physiological function for dehydrins in certain plant cells during optimal growth
      conditions and in most cell types during ABA or cold treatment. The differences
      in stress specificity and spatial distribution of dehydrins in Arabidopsis
      suggest a functional specialization for the members of this protein family.

PMID- 11292074
TI  - Analysis of carotenoid biosynthetic gene expression during marigold petal
      development.
AB  - Marigold (Tagetes erecta L.) flower petals synthesize and accumulate carotenoids
      at levels greater than 20 times that in leaves and provide an excellent model
      system to investigate the molecular biology and biochemistry of carotenoid
      biosynthesis in plants. In addition, marigold cultivars exist with flower colors
      ranging from white to dark orange due to >100-fold differences in carotenoid
      levels, and presumably similar changes in carbon flux through the pathway. To
      examine the expression of carotenoid genes in marigold petals, we have cloned the
      majority of the genes in this pathway and used these to assess their steady-state
      mRNA levels in four marigold cultivars with extreme differences in carotenoid
      content. We have also cloned genes encoding early steps in the biosynthesis of
      isopentenyl pyrophosphate (IPP), the precursor of all isoprenoids, including
      carotenoids, as well as two genes required for plastid division. Differences
      among the marigold varieties in the expression of these genes suggest that
      differences in mRNA transcription or stability underlie the vast differences in
      carotenoid synthesis and accumulation in the different marigold varieties.

PMID- 11292076
TI  - The plastid chromosome of spinach (Spinacia oleracea): complete nucleotide
      sequence and gene organization.
AB  - The chloroplast chromosome of spinach (Spinacia oleracea) is a double-stranded
      circular DNA molecule of 150,725 nucleotide pairs. A comparison of this
      chromosome with those of the three other autotrophic dicotyledons for which
      complete DNA sequences of plastid chromosomes are available confirms a conserved
      overall structure. Three classes of open reading frames were distinguished: (1)
      genes of known function which include 108 unique loci, (2) three hypothetical
      chloroplast reading frames (ycfs) that are highly conserved interspecifically,
      and (3) species-specific or rapidly diverging 'open reading frames'. A detailed
      transcript study of one of the latter (ycf15) shows that these loci may be
      transcribed, but do not constitute protein-coding genes.

PMID- 11292075
TI  - Genotype-dependent differences in S12-RNase expression lead to sporadic self
      compatibility.
AB  - Sporadic self-compatibility, the occasional fruit formation after otherwise
      incompatible pollinations, has been observed in some S12-containing genotypes of
      Solanum chacoense but not in others. We have sequenced this S12 allele and
      analyzed its expression in four different genotypes. The S12-RNase levels were
      generally less abundant than those of other S-RNases present in the same plants.
      In addition, two-fold and five-fold differences in the amount of S12-RNase and
      S12 RNA, respectively, were observed among the genotypes analyzed. A comparison
      with the genetic data showed that genotypes with the highest levels were fully
      and permanently self-incompatible, whereas those with the lowest levels were
      those in which sporadic self-compatibility had been observed. The mature protein
      contains four potential glycosylation sites and genotype-specific differences in
      the pattern of glycosylation are also observed. Our results suggest the presence
      of modifier genes which affect, in a genotype-dependent manner, the level of
      expression and the post-translational modification of the S12-RNase.

PMID- 11292077
TI  - Protein import into plant mitochondria: precursor proteins differ in ATP and
      membrane potential requirements.
AB  - The import pathways of the alternative oxidase and the F(A)d subunit of the ATP
      synthase from soybean were characterised. The F(A)d precursor does not require
      extramitochondrial ATP for import and this was shown to be a characteristic of
      the mature protein. The alternative oxidase and F(A)d precursors were shown to
      differ in their requirement for a membrane potential. The membrane potential was
      modified using malonate, a competitive inhibitor to complex II. The alternative
      oxidase could be imported at higher malonate concentrations compared to the
      F(A)d. This difference could not be ascribed to the number of positive charges in
      each presequence as would be predicted from similar studies in fungi.

PMID- 11292078
TI  - The stress- and abscisic acid-induced barley gene HVA22: developmental regulation
      and homologues in diverse organisms.
AB  - Abscisic acid (ABA) induces the expression of a battery of genes in mediating
      plant responses to environmental stresses. Here we report one of the early ABA
      inducible genes in barley (Hordeum vulgare L.), HVA22, which shares little
      homology with other ABA-responsive genes such as LEA (late embryogenesis
      abundant) and RAB (responsive to ABA) genes. In grains, the expression of HVA22
      gene appears to be correlated with the dormancy status. The level of HVA22 mRNA
      increases during grain development, and declines to an undetectable level within
      12 h after imbibition of non-dormant grains. In contrast, the HVA22 mRNA level
      remains high in dormant grains even after five days of imbibition. Treatment of
      dormant grains with gibberellin (GA) effectively breaks dormancy with a
      concomitant decline of the level of HVA22 mRNA. The expression of HVA22 appears
      to be tissue-specific with the level of its mRNA readily detectable in aleurone
      layers and embryos, yet undetectable in the starchy endosperm. The expression of
      HVA22 in vegetative tissues can be induced by ABA and environmental stresses,
      such as cold and drought. Apparent homologues of this barley gene are found in
      phylogenetically divergent eukaryotic organisms, including cereals, Arabidopsis,
      Caenorhabditis elegans, man, mouse and yeast, but not in any prokaryotes.
      Interestingly, similar to barley HVA22, the yeast homologue is also stress
      inducible. These observations suggest that the HVA22 and its homologues encode a
      highly conserved stress-inducible protein which may play an important role in
      protecting cells from damage under stress conditions in many eukaryotic
      organisms.

PMID- 11292079
TI  - The low-temperature- and salt-induced RCI2A gene of Arabidopsis complements the
      sodium sensitivity caused by a deletion of the homologous yeast gene SNA1.
AB  - Two closely related, tandemly arranged, low-temperature- and salt-induced
      Arabidopsis genes, corresponding to the previously isolated cDNAs RCI2A and
      RCI2B, were isolated and characterized. The RCI2A transcript accumulated
      primarily in response to low temperature or high salinity, and to a lesser extent
      in response to ABA treatment or water deficit stress. The RCI2B transcript was
      present at much lower levels than RCI2A, and could only be detected by reverse
      transcription-PCR amplification. The predicted 6 kDa RCI2 proteins are highly
      hydrophobic and contain two putative membrane-spanning regions. The polypeptides
      exhibit extensive similarity to deduced low-temperature- and/or salt-induced
      proteins from barley, wheat grass and strawberry, and to predicted proteins from
      bacteria, fungi, nematodes and yeast. Interestingly, we found that a deletion of
      the RCI2 homologous gene, SNA1 (YRD276c), in yeast causes a salt-sensitive
      phenotype. This effect is specific for sodium, since no growth defect was
      observed for the sna1 mutant on 1.7 M sorbitol, 1 M KCl or 0.6 M LiCl. Finally,
      we found that the Arabidopsis RCI2A cDNA can complement the sna1 mutant when
      expressed in yeast, indicating that the plant and yeast proteins have similar
      functions during high salt stress.

PMID- 11292080
TI  - Molecular cloning and functional characterization of two kinds of betaine
      aldehyde dehydrogenase in betaine-accumulating mangrove Avicennia marina (Forsk.)
      Vierh.
AB  - Glycinebetaine is an important osmoprotectant in bacteria, plants, and animals,
      but only little information is available on the synthesis of glycinebetaine in
      tree plants. Among four mangrove species, glycinebetaine could be detected only
      in Avicennia marina. Pinitol was the main osmoprotectant in the other three
      species. The level of glycinebetaine in A. marina increased under high salinity.
      Betaine-aldehyde dehydrogenase (BADH) was detected in all four species, but
      choline monooxygenase could not be detected. A cDNA library was constructed from
      the leaves of A. marina. Two kinds of BADH cDNAs were isolated, one homologous to
      the spinach chloroplast BADH, and the other with unique residues SKL at the end
      of C-terminus. The BADH transcription levels of the former were higher than those
      of the latter. The levels of the former BADH increased at high salinity whereas
      those of the latter were independent of salinity. BADHs were expressed in
      Escherichia coli and purified. Two kinds of A. marina BADHs exhibited similar
      kinetic and stability properties, but were significantly different from those of
      spinach BADH. A. marina BADHs efficiently catalyzed the oxidation of
      betainealdehyde, but not the oxidation of omega-aminoaldehydes and were more
      stable at high temperature than the spinach BADH.

PMID- 11292082
TI  - Black intraocular lens for leukocoria.

PMID- 11292081
TI  - Further analysis of the interactions between the Brassica S receptor kinase and
      three interacting proteins (ARC1, THL1 and THL2) in the yeast two-hybrid system.
AB  - The yeast two-hybrid system was used to further characterize the interactions
      between the Brassica S receptor kinase (SRK) and three putative substrates, ARC1
      and the two thioredoxin h proteins, THL1 and THL2. Interactions were generally
      detectable with kinase domains of both Class I and Class II SRKs. Chimeric
      constructs were made between the SRK910 kinase domain and the non-interacting
      Arabidopsis RLK5 kinase domain. Only one chimeric construct, SRR2, interacted
      with THL1 and THL2, while none of the chimeras were able to interact with ARC1.
      SRR2 is largely made up of RLK5 kinase domain with the N-terminal end being
      derived from the SRK910 kinase domain and was the only chimeric construct that
      retained kinase activity. Deletion or substitution of a conserved cysteine at the
      N-terminal end of the SRK910 kinase domain resulted in loss of interaction with
      THL1 and THL2, while the addition of this cysteine to a related receptor kinase,
      SFR1, conferred the ability to interact with the thioredoxin h proteins. In
      addition, substitution of the cysteines in the THL1 active site abolished the
      interaction. Lastly, the two Arabidopsis thioredoxin h clones most closely
      related to THL1 and THL2 were found to interact with the SRK kinase domains.
      Thus, the nature of the interaction of the thioredoxin h clones with SRK involves
      the reducing activity of these proteins and is restricted to the class of
      thioredoxin h proteins which have the variant CPPC active site.

PMID- 11292083
TI  - Foot-and-mouth disease: efforts  continue to stamp out the virus.

PMID- 11292084
TI  - Outbreak of foot-and-mouth disease virus serotype O in the UK caused by a
      pandemic strain.

PMID- 11292085
TI  - Presence of Mycobacterium avium subspecies paratuberculosis in suspensions of
      ovine trichostrongylid larvae produced in faecal cultures artificially
      contaminated with the bacterium.
AB  - A reference strain of Mycobacterium avium subspecies paratuberculosis was added
      to faecal larval cultures of Haemonchus contortus, Ostertagia circumcincta and
      Trichostrongylus colubriformis. Samples of the larvae produced were cultured for
      the presence of the bacterium in modified BACTEC 12B medium, both before and
      after exposure to gamma irradiation. The water used to wash the larvae off the
      faecal cultures was also tested for the presence of the bacterium. Positive
      growth was confirmed as M. avium subspecies paratuberculosis by IS900 polymerase
      chain reaction and restriction endonuclease analysis of the product. M. avium
      subspecies paratuberculosis was detected in the unirradiated larval suspensions
      and wash waters of all three nematode species, and in the irradiated H. contortus
      larval suspension.

PMID- 11292086
TI  - Minimal alveolar concentration of desflurane in combination with an infusion of
      medetomidine for the anaesthesia of ponies.
AB  - The minimum alveolar concentration of desflurane when combined with a continuous
      infusion of medetomidine at 3.5 microg/kg/hour was measured in seven ponies.
      Anaesthesia was induced with medetomidine (7 microg/kg intravenously) followed by
      ketamine (2 mg/kg intravenously) and maintained with desflurane in oxygen. The
      infusion of medetomidine was started 20 minutes after the induction of
      anaesthesia. The electrical test stimulus was applied at the coronary band (50 V,
      10 ms bursts at 5 Hz for one minute), and heart rates and rhythms, arterial blood
      pressures, and arterial blood gas tensions were measured at intervals, just
      before the application of the stimulus. The mean (sd) minimum alveolar
      concentration of desflurane was 5.3 (1.04) per cent (range 3.2 to 6.4 per cent),
      28 per cent less than the previously published value for desflurane alone after
      the induction of anaesthesia with xylazine and ketamine. The cardiopulmonary
      parameters remained stable throughout the period of anaesthesia. The mean (sd)
      time taken by the ponies to stand after the administration of desflurane ceased
      was 16.5 (6.17) (range 5.8 to 26) minutes, and the quality of recovery was good
      or excellent. However, one pony died shortly after standing; a postmortem
      examination revealed that it had chronic left atrial dilatation.

PMID- 11292087
TI  - Postmortem biochemical markers of experimentally induced hypomagnesaemic tetany
      in cattle.
AB  - Severe hypomagnesaemia and tetany were induced in 10 lactating cows by feeding
      them semi-synthetic low magnesium diets and the animals were used to study the
      stability of postmortem markers of hypomagnesaemic tetany. There were significant
      relationships between the concentrations of magnesium in either cerebrospinal
      fluid (CSF) or plasma and either aqueous or vitreous humour. The onset of
      hypomagnesamic tetany was also associated with low magnesium concentrations in
      plasma, CSF and aqueous and vitreous humour. Magnesium concentrations less than
      0.25 mmol/litre in fresh aqueous humour may be indicative of severe
      hypomagnesaemia and possible tetany in lactating cows, but the concentration of
      magnesium in aqueous humour was unstable postmortem. The concentration of
      magnesium in vitreous humour was relatively stable and a concentration of less
      than 0.55 mmol/litre could be used as a diagnostic marker of tetany in cattle for
      up to at least 48 hours postmortem, at ambient temperatures typical of Northern
      Ireland.

PMID- 11292088
TI  - Clinical recognition and treatment of bovine cutaneous actinobacillosis.

PMID- 11292089
TI  - Diabetes mellitus associated with lymphocytic islet inflammation in a Charolais
      bull.

PMID- 11292090
TI  - Megacolon secondary to autonomic ganglioneuritis in a dog.

PMID- 11292091
TI  - Effect of environmental temperature on quality and developmental competence in
      vitro of buffalo oocytes.

PMID- 11292092
TI  - Foot-and-mouth disease outbreak.

PMID- 11292093
TI  - Foot-and-mouth disease outbreak.

PMID- 11292094
TI  - Foot-and-mouth disease outbreak.

PMID- 11292095
TI  - Porcine dermatitis and nephropathy syndrome.

PMID- 11292096
TI  - Ivermectin-resistant Cooperia in cattle.

PMID- 11292097
TI  - Arcanobacterium/Corynebacterium-like bacterial isolates from sheep.

PMID- 11292098
TI  - Angiostrongylus vasorum in dogs.

PMID- 11292099
TI  - Veterinary Benevolent Fund.

PMID- 11292100
TI  - Promoting a future without tobacco: also a continuing task for respiratory
      medicine in Europe.

PMID- 11292101
TI  - Management of chronic obstructive pulmonary disease: are we going anywhere?

PMID- 11292102
TI  - Patients hospitalized for COPD have a high prevalence of modifiable risk factors
      for exacerbation (EFRAM study).
AB  - There is little information available concerning the extent to which chronic
      obstructive pulmonarv disease (COPD) patients are satisfactorily managed,
      especially, regards factors supposedly related to COPD exacerbation. The present
      study assessed the prevalence rates of potentially modifiable risk factors of
      COPD exacerbation in patients hospitalized for this reason. A systematic sample
      of one out of two patients admitted for COPD exacerbation, during 1 yr, in four
      tertiary hospitals in the Barcelona area, Spain, was performed. Patients answered
      a questionnaire and underwent anthropometric measurements, spirometric tests and
      arterial blood gas sampling. Prevalence rates and 95% confidence intervals (95%
      CI) for risk factors were obtained, and the generalized estimating equation (GEE)
      method was used to allow for patients to provide information on different
      admissions. The study recruited 353 patients (29 female) with a total of 404
      admissions age (mean+/-SD) 69+/-9, median forced expiratory volume in one second
      (FEV1) 31% of predicted and mean partial pressure of oxygen (PO2) 63+/-13 mmHg.
      Of these, 28% had not received an influenza vaccination; a high number (86%) did
      not attend rehabilitation programmes; 28% of patients with PO2 < or =55 mmHg were
      not using long-term oxygen therapy (LTOT); among LTOT users, 18% used it <15 h a
      day; 43% of the total failed in some of the essential inhaler manoeuvres; 26%
      were current smokers; 21% of noncurrent smokers were exposed to passive smoking
      at home; current occupational exposure was low (5%). In summary, the authors
      found a moderate to high prevalence of potentially modifiable risk factors in a
      large representative sample of patients hospitalized for a chronic obstructive
      pulmonary disease exacerbation, suggesting unsatisfactory features in their
      management.

PMID- 11292103
TI  - Lung volume reduction surgery versus conservative treatment in severe emphysema.
AB  - Lung volume reduction surgery (LVRS) has been proposed for patients with severe
      emphysema to improve dyspnoea and pulmonary function. It is unknown, however,
      whether prognosis and pulmonary function in these patients can be improved
      compared to conservative treatment. The effect of LVRS and conservative therapy
      were compared prospectively in 57 patients with emphysema, who fulfilled the
      standard criteria for LVRS. The patients were divided into two groups according
      to their own decision. Patients in group 1 (n=29, eight females, mean+/-SEM
      58.8+/-1.7 yrs, forced expiratory volume in one second (FEV1) 27.6+/-1.3% of the
      predicted value) underwent LVRS. Patients in group 2 (n=28, five females, 58.5+/
      1.8 yrs, FEV1 30.8+/-1.4% pred) preferred to postpone LVRS. There were no
      significant differences in lung function between the two groups at baseline;
      however, there was a tendency towards better functional status in the control
      group. The control group had a better modified Medical Research Council (MMRC)
      dyspnea score (3.1+/-0.15 versus 3.5+/-0.1, p<0.04). Model-based comparisons were
      used to estimate the differences between the two groups over 18 months.
      Significant improvements were observed in the LVRS group compared to the control
      group in FEV1, total lung capacity (TLC), Residual volume (RV), MMRC dyspnea
      score and 6-min walking distance on all follow up visits. The estimated
      difference in FEV1 was 33% (95% confidence interval 13-58%; p>0.0001), in TLC
      12.9% (7.9-18.8%; p>0.0001), in RV 60.9% 32.6-89.2%; p>0.0001), in 6-min walking
      distance 230 m (138-322 m; p<0.002) and in MMRC dyspnoea score 1.17 (0.79-1.55;
      p<0.0001). In conclusion, lung volume reduction surgery is more effective than
      conservative treatment for the improvement of dyspnoea, lung function and
      exercise capacity in selected patients with severe emphysema.

PMID- 11292104
TI  - Prevalence and consequences of nutritional depletion in lung transplant
      candidates.
AB  - Nutritional status was studied in lung transplant (LT) candidates. The hypotheses
      were that nutritional depletion was highly prevalent and lean body mass depletion
      was a risk factor for a higher mortality both before and after LT. Of 78
      consecutive patients listed for LT, 16 (21%) died while on the waiting list,
      eight (10%) were alive awaiting LT, and 54 (69%) received a graft. Mean age was
      42.3+/-4.4 (mean+/-SD). Thirty-eight per cent had a diagnosis of bronchiectasis
      or cystic fibrosis (BRO/CF), 33% of emphysema, 20% of idiopathic pulmonary
      fibrosis (IPF) and 8% of primary pulmonary hypertension. Body mass index (BMI)
      was 20.4+/-4.3 kg.m2, weight was 87.9+/-16.6% of ideal body weight (IBW).
      Patients were classed into four nutritional groups according to IBW and
      creatinine height index (CHI): 1: weight <90% IBW and CHI <60% of predicted (28%
      of cases); II: weight <90% IBW and CHI > or =60% (27%); III: weight > or =90% IBW
      and CHI <60% (17%); IV: weight > or =90% IBW and CHI > or =60% (28%). Overall,
      72% were depleted corresponding to groups 1, II and III. Lean body mass depletion
      occurred despite normal weight in 17% of the cases (group III). Subjects with
      BRO/CF were mostly in groups 1, II, III whereas IPF were concentrated in group
      II. Lean body mass depletion was associated with more severe hypoxaemia, reduced
      6-minute walking distance and a higher mortality while awaiting. After LT,
      duration of mechanical ventilation, time spent in intensive care unit (ICU) was
      related to initial body composition. Survival after LT was lowest in group III.
      To conclude, nutritional depletion in lung transplant candidates is highly
      prevalent and should be more precisely assessed with a special reference to lean
      body mass since it has specific consequences both while awaiting and after lung
      transplant. Attempts should be made to increase lean body mass before lung
      transplant.

PMID- 11292105
TI  - A model for predicting life expectancy of children with cystic fibrosis.
AB  - In this study the authors aimed to produce a model for predicting the life
      expectancy of children with severe cystic fibrosis (CF) lung disease. The
      survival of 181 children with severe CF lung disease referred for transplantation
      assessment 1988-1998 (mean age 11.5 yrs, median survival without transplant 1.9
      yrs from date of assessment) were studied. Proportional hazards modelling was
      used to identify assessment measurements that are of value in predicting
      longevity. The resultant model included low height predicted forced expiratory
      volume in one second (FEV1), low minimum oxygen saturation (Sa,O2min) during a 12
      min walk, high age adjusted resting heart rate, young age, female sex, low plasma
      albumin, and low blood haemoglobin as predictors for poor prognosis.
      Extrapolation from the model suggests that a 12-yr old male child with an FEV1 of
      30% pred and a Sa,O2min of 85% has a 44% risk of death within 2 yrs (95%
      confidence interval (CI) 35-54%), whilst a female child with the same
      measurements has a 63% risk of death (95% CI 52-73%) within the same period. The
      model produced may be of value in predicting the life expectancy of children with
      severe cystic fibrosis lung disease and in optimizing the timing of lung
      transplantation.

PMID- 11292106
TI  - The effect of prelung transplant clinical status on post-transplant survival of
      children with cystic fibrosis.
AB  - The aim of this study was to determine whether transplanting paediatric cystic
      fibrosis (CF) patients later in the course of their disease was detrimental to
      their post-transplant survival. Data was collected from 51 children with CF
      undergoing lung or heart-lung transplantation May 1988-March 1999. The following
      risk factors were tested by Cox proportional hazards modelling: age at
      transplant; sex; donor/recipient sex mismatch; donor/recipient cytomegalovirus
      (CMV) mismatch; cold and warm graft ischaemic times; and donor age. Pretransplant
      forced expiratory volume in one second (FEV1), minimum oxygen saturation obtained
      during 12 min walk (Sa,O2min), and a survival probability score (SP) calculated
      from FEV1, age adjusted resting heart rate, age, sex, blood haemoglobin (Hb), and
      serum albumin were then added to the model. None of the risk factors were
      significantly correlated with death during the study period. No evidence that
      clinical status prior to transplant has any effect upon the post-transplant
      survival of children with cystic fibrosis was found.

PMID- 11292107
TI  - Breath isoprene during acute respiratory exacerbation in cystic fibrosis.
AB  - Patients with cystic fibrosis (CF) experience a combination of chronic systemic
      oxidative stress, generation of free radicals in the lungs due to a hyperimmune
      response and a diminished ability to scavenge free radicals secondary to
      malabsorption and increased consumption. The authors asked the question, "Does
      breath isoprene content reflect systemic oxidative stress?" The study involved 12
      CF patients and 12 matched healthy controls. The patients were sampled during
      acute respiratory exacerbation (increased respiratory symptoms, reduction in
      forced expiratory volume (FEV1) of >10%, and a decision to treat with intravenous
      antibiotics) and after two weeks of antibiotic treatment. Blood samples were
      examined for markers of oxidative stress. Breath samples were analysed for
      isoprene content. Malondialdehyde (MDA), erythrocyte membrane polyunsaturated
      fatty acids, protein sulphydryls and protein carbonyls all showed evidence of
      increased oxidative stress which was moderated by antibiotic treatment. Breath
      isoprene production rate was significantly lower in patients during exacerbation
      than in controls with a mean difference of-39 (95% confidence interval (CI) -11
      57) pmol.min.kg(-1) and increased to normal values following treatment (mean
      change 63 (95% CI 42-84) pmol.min.kg(-1)). In conclusion, breath isoprene cannot
      be considered a reliable marker of oxidative stress.

PMID- 11292108
TI  - Performance of forced expiratory manoeuvre in children.
AB  - The negative expiratory pressure (NEP) method has been previously used to assess
      the performance of forced vital capacity (FVC) manoeuvre in normal adults. The
      aim of the present study is to assess whether flow limitation is achieved during
      FVC manoeuvres in children aged 6-14 yrs. NEP (-10 cmH2O) was successfully
      applied in 177 normal children, the portion of FVC over which expiratory flow did
      or did not change with NEP being taken as effort-dependent and effort
      independent, respectively. In all children peak expiratory flow (PEF) and forced
      expiratory volume in one second (FEV1) increased with NEP, indicating that PEF
      was in the effort-dependent portion of FVC. This portion decreased significantly
      with age (50-20% of FVC from 6-14 yrs). It is suggested that this mainly reflects
      the poorer coordination of specialized motor acts in younger children because of
      incomplete morphological and functional maturation of the relevant central
      nervous system (CNS) mechanisms. The results indicate that most unexperienced
      children aged 6-14 yrs can perform acceptable forced vital capacity manoeuvres,
      eventually achieving flow limitation over a portion of the forced vital capacity
      that increases with age. The negative expiratory pressure method can be used for
      online assessment of the performance of forced vital capacity manoeuvres and
      evaluation of treatment-related effects.

PMID- 11292110
TI  - Respiratory inductance plethysmography in healthy infants: a comparison of three
      calibration methods.
AB  - Respiratory inductance plethysmography (RIP) measures respiration from body
      surface movements. Various techniques have been proposed for calibration in order
      that RIP may be used quantitatively. These include calculation of the
      proportionality constant of ribcage to abdominal volume change (K). The aims of
      this study were to 1) establish whether a fixed value of K could be used for
      calibration, and 2) compare this technique with multiple linear regression (MLR)
      and qualitative diagnostic calibration (QDC) in normal healthy infants.
      Recordings of pneumotachograph (PNT) flow and RIP were made during quiet (QS) and
      active sleep (AS) in 12 infants. The first 5 min in a sleep state were used to
      calculate calibration factors, which were applied to subsequent validation data.
      The absolute percentage error between RIP and PNT tidal volumes was calculated.
      The percentage error was similar over a wide range of K during QS. However, K
      became more critical when breathing was out of phase. A standard for K of 0.5 was
      chosen. There was good agreement between calibration methods during QS and AS. In
      the first minute following calibration during QS, the mean absolute errors were
      3.5, 4.1 and 5.3% for MLR, QDC and fixed K respectively. The equivalent errors in
      AS were 11.5, 13.1 and 13.7% respectively. The simple fixed ratio method can be
      used to measure tidal volume with similar accuracy to multiple linear regression
      and qualitative diagnostic calibration in healthy unsedated sleeping infants,
      although it remains to be validated in other groups of infants, such as those
      with respiratory disease.

PMID- 11292109
TI  - Ventilatory variables in normal children during rest and exercise.
AB  - The aim of this study was to provide a complete description of normal ventilation
      at rest and exercise in children and to determine how best to correct for body
      size. One-hundred and six children aged 8-17 years (55 male) underwent
      incremental bicycle exercise testing from rest to exhaustion in 3 min, 15 W.m(-2)
      steps and thence through 9 min recovery. All variables were calculated using
      helium dilution mixed expired gas analysis together with measures of alveolar gas
      concentrations from continuous measurement at the mouth, all via an AMIS 2000
      quadrupole mass spectrometer. Surface area was the best single measure to correct
      for body size but always explained <37% of the variance. Thus for example,
      surface area corrected oxygen consumption at rest in males was greater than
      females. Data is presented at rest, each work load and at "maximum" exercise.
      When presented per watt of work at each work load, this permits comparison of
      adaptability to exercise between sexes and age groups. Exercise appears to
      terminate when respiration reaches 45 and 40 breaths-min(-1) in males and females
      respectively and when alveolar oxygen concentrations rise. This simple protocol
      and near complete data set ought to permit accurate comparison with disease
      groups.

PMID- 11292111
TI  - Increased frequency of asymptomatic bronchial hyperresponsiveness in nonasthmatic
      patients with food allergy.
AB  - Subclinical inflammation in gut mucosa has been demonstrated in bronchial asthma
      suggesting the whole mucosal system is involved in allergic diseases. The
      presence of subclinical bronchial involvement was assessed by nonspecific
      bronchial hyperresponsiveness (BHR) in nonasthmatic patients with food allergy
      (FA). BHR was studied in 35 patients with various manifestations of FA without
      food-induced asthma. Sixteen had a previous history of asthma and/or rhinitis to
      aeroallergens (group A), whereas 19 patients (group B) did not. BHR was defined
      by a provocative dose causing a 20% fall in forced expiratory volume in one
      second of (PC20) <8 mg.mL(-1) of methacholine. Asymptomatic BHR occurred
      frequently in nonasthmatic patients with FA (10 of 19, 53%); this did not
      significantly differ from patients with FA and a previous history of asthma
      and/or rhinitis to aeroallergens (13 of 16, 81%). PC20 was significantly lower in
      group A (1.84+/-0.53 mg.mL(-1)) than in group B (3.35+/-0.74 mg.mL(-1); p<0.05).
      The number of patients with positive skin tests to aeroallergens was similar
      between groups. Sequential evaluation, performed 1 year after initial evaluation,
      in 7 nonasthmatic patients (group B) demonstrated a similar level of BHR. The
      present study demonstrated that BHR is a frequent finding in nonasthmatic
      patients with food allergy which may be due, at least in part, to a subclinical
      inflammatory process in the bronchi.

PMID- 11292112
TI  - Induced sputum eosinophils and neutrophils and bronchiectasis severity in
      allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to
      the fungus Aspergillus fumigatus that may progress to bronchiectasis. The aim of
      the present study was to characterize airway inflammation in patients with
      clinically stable ABPA and asthma, and to correlate this with bronchiectasis
      severity. Subjects with ABPA and central bronchiectasis (ABPA-CB; n=16) and ABPA
      with serological evidence alone (ABPA-S; n=10) were studied. Comparison groups
      were A. fumigatus-sensitized asthma (n=19), non-A. fumigatus-sensitized asthma
      (n=15) and healthy controls (n=8). Hypertonic saline challenge, sputum induction
      and high-resolution computed tomography (HRCT) of the chest were performed.
      Sputum eosinophil numbers were markedly elevated in ABPA-CB (median 8.4%)
      compared to ABPA-S (2.4%), A. fumigatus-sensitized asthma (1.8%), asthma (1.8%)
      and controls (0.3%) (p<0.01); sputum eosinophil cationic protein levels were
      higher in ABPA-CB (median 13,706 ng.mL(-1)), compared to ABPA-S (1,633.5 ng.mL(
      1)), A. fumigatus-sensitized asthma (1,550.7 ng.mL(-1)), asthma (309.2 ng.mL(
      1)), and controls (110 ng.mL(-1)) (p<0.001). ABPA-CB also showed increased sputum
      neutrophil number (median 60.3%) compared to the other groups (controls 29.3%)
      (p=0.01). The severity of bronchiectasis on HRCT correlated with sputum
      neutrophil (r=0.6) and eosinophil number (r=0.5) but not serum immunoglobulin-E
      levels. In conclusion, clinically stable allergic bronchopulmonary aspergillosis
      with bronchiectasis is characterized by an intense heterogenous inflammatory
      infiltrate consisting of eosinophils and neutrophils, which correlates closely
      with the severity of bronchiectasis on high-resolution computed tomography.
      Sputum analysis may be useful in monitoring the course of allergic
      bronchopulmonary aspergillosis.

PMID- 11292113
TI  - Inhaled isotonic alkaline versus saline solution and radioaerosol clearance in
      chronic cough.
AB  - The aim of the present study was to test the influence of inhaled isotonic Ems
      salt (brine from the spa of Bad Ems, Germany) compared to isotonic saline on
      radioaerosol clearance (RC) in patients with chronic cough. Ems salt is an
      alkaline solution (pH 8.0-9.0) containing largely bicarbonate ions rather than
      the chloride ions present in isotonic saline (pH 6.4). RC was assessed with a
      radioaerosol technique using technetium-99m albumin in supine patients. After a
      30-min baseline measurement of RC according to a single blind and randomized
      design, patients inhaled Ems salt (n=22, 20-77 yrs) or isotonic saline (n=21, 34
      72 yrs) via a jet nebulizer (Pari Boy) for 10 min and were scanned for an
      additional 30 min. There was no difference between the two groups before
      intervention in terms of deposition pattern, lung function and baseline RC rate.
      After inhalation of Ems salt, the RC rate (1/tau) improved significantly from
      0.15+/-0.14 (mean+/-SD) to 0.53+/-0.70 L.h(-1) (p<0.005); no change was found
      after isotonic saline (0.13+/-0.13 to 0.08+/-0.09 L.h(-1), NS). Voluntary coughs
      performed after 60 min had no effect on the RC rate. However, in the Ems salt
      group, significantly more patients reported an inhalation induced cough. Compared
      to the Ems salt patients, who did not cough during and after inhalation, the RC
      rate in the cough group was enhanced significantly (0.10+/-0.12 versus 0.73+/
      0.83, p=0.017), this effect being seen more frequently in females (p=0.003). It
      is concluded that Ems salt improves radioaerosol clearance significantly in
      patients with chronic cough. The underlying mechanism, regarding whether induced
      cough, increased water content in the mucus or enhanced ciliary beat frequency is
      the leading cause of Ems salt action, remains unclear.

PMID- 11292114
TI  - Chronic cough in children: bronchoalveolar lavage findings.
AB  - Isolated chronic cough in childhood is a common complaint. Although the symptom
      cough is included in the definition of clildhood asthma, there is debate as to
      whether the majoritv of these children have asthma. The authors studied children
      with isolated chronic cough looking for evidence of airway inflammation typical
      of asthma, with increased numbers of airway eosinophils as assessed from
      bronchoalveolar lavage (BAL). The investigations were carried out on 23 children
      (median age: 6.7 yrs; range: 1.7-12.75 yrs), attending the Royal Belfast Hospital
      for Sick Children for elective surgery, who also had a chronic unexplained cough.
      Written informed consent was obtained from the parent(s) and a nonbronchoscopic
      BAL was performed. BAL samples were analysed for total and differential white
      cell counts and also for the inflammatory mediators, eosinophil cationic protein
      (ECP) and histamine. Results were compared with a group of normal nonatopic
      children and also a group of atopic asthmatic children, who had been recruited
      for other studies on airway inflammation. There was a small but statistically
      significant increase in BAL percentage eosinophils in the children with chronic
      cough compared with nonasthmatic controls (0.28% versus 0.10%, p=0.03). However,
      the children with cough had lower percentage eosinophils than the atopic
      asthmatic controls (0.28% versus 0.66%, p=0.01). Three out of 23 children with
      chronic cough had BAL eosinophils greater than the normal upper 95% reference
      interval in BAL. There was a small but statistically significant increase in
      percentage neutrophils in the children with cough compared with the nonasthmatic
      controls (5.85% versus 3.21%, p=0.03). Four out of the 23 children had BAL
      neutrophils greater than the normal upper 95% reference interval in BAL. The
      authors conclude that only a minority of children with chronic unexplained cough
      have asthmatic-type airway inflammation. It is speculated that the increased
      percentage neutrophils in bronchoalveolar lavage from children with cough could
      relate to underlying persistent airways infection.

PMID- 11292115
TI  - The concentration of hydrogen peroxide in exhaled air depends on expiratory flow
      rate.
AB  - Hydrogen peroxide (H2O2) is known to be detectable in exhaled air. The present
      study aimed to determine whether the concentration of exhaled H2O2 depends on
      expiratory flow rate in order to make inferences on the site of its production
      within the lung. Breath condensate was collected in cooled Teflon tubes, at three
      different expiratorv flow rates, in 15 healthy or mild asthmatic subjects. Tests
      were repeated 2-5 times to assess reproducibility. Mean+/-SEM concentrations of
      H2O2 at flow rates of 140, 69 and 48 mL.s(-1) were 0.12+/-0.02, 0.19+/-0.02 and
      0.32+/-0.03 microM, respectively. These values differed significantly from each
      other (p<0.001). For comparison, average coefficients of variability within
      repeated measurements at each of the three flow rates were 68, 62 and 82%,
      respectively. These data demonstrate that the concentration of exhaled hydrogen
      peroxide depends on expiratory flow rate. Since flow dependence is an indicator
      of production within the airways, this result suggests that, to a large extent,
      the exhaled hydrogen peroxide originates within the airways. However, even under
      strictly controlled conditions, a high degree of variability persists, which may
      limit the usefulness of exhaled hydrogen peroxide as a marker of airway
      inflammation.

PMID- 11292116
TI  - Lipid-laden macrophages in induced sputum are a marker of oropharyngeal reflux
      and possible gastric aspiration.
AB  - The diagnostic properties of a "lipid index" of macrophages in induced sputum as
      a noninvasive marker of aspiration of acidic gastric contents were evaluated. In
      a cross-sectional study, 33 subjects (17 with symptoms suggestive of
      gastrooesophageal reflux) with normal chest radiographs and no symptoms of
      aspiration or sinus disease, underwent dual-channel 24-h ambulatory oesophageal
      pH recording and sputum induction. Oropharyngeal reflux, defined as at least one
      episode of a fall in pH to <4 at the upper oesophageal electrode, was considered
      indicative of aspiration of acidic gastric contents ("gold standard"). An index
      for the presence of intracellular lipid in sputum macrophages, detected by oil
      red O stain, was obtained. The sensitivity, specificity and predictive values of
      this "lipid index" were calculated. The "lipid index" could be calculated in 29
      of 33 samples with high interobserver repeatability (intraclass correlation
      coefficient 0.96). Twenty subjects showed oropharyngeal reflux and nine did not.
      The median "lipid index" in subjects with oropharyngeal reflux (24.5) was
      significantly greater than that in those without reflux (1.0) (p<0.001). A "lipid
      index" of 7.0 had a sensitivity of 90%, a specificity of 89%, a positive
      predictive value of 95% and a negative predictive value of 80%. A "lipid index"
      of 7.0 in the macrophages of induced sputum is a good marker of oropharyngeal
      reflux.

PMID- 11292117
TI  - Inhibition of airway smooth muscle tone by Chinese herbal medicines.
AB  - The aim of the present study was to elucidate whether Chinese traditional herbal
      drugs, Gorei-San (TJ-17) and Toki-Shakuyaku-San (TJ-23), affect airway smooth
      muscle tone and, if so, to determine what the mechanism of action is. Rabbit
      tracheal segments were isolated and the contractile responses to electrical field
      stimulation and acetylcholine were measured before and after the application of
      TJ-17 or TJ-23 under isometric conditions in vitro. Ouabain-sensitive rubidium-86
      (86Rb) uptake by tissues in response to each drug was also measured. Each herbal
      medicine attenuated the contractile responses to electrical field stimulation and
      acetylcholine in a concentration-dependent manner, the maximal inhibition of
      acetylcholine-induced contraction being 37.5+/-4.9% for TJ-17 and 42.4+/-5.3% for
      TJ-23 (p<0.05 for each). These effects were not altered by mechanical removal of
      the epithelium, indomethacin, the nitric oxide synthase inhibitor NG -nitro-L
      arginine methyl ester, the cyclic adenosine monophosphate (cAMP)-dependent
      protein kinase inhibitor adenosine 3'5'-cyclic monophosphorothioate (Rp-cAMPS),
      the cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor
      KT5823, or the calcium (Ca2+)-activated potassium (K+) channel inhibitor
      charybdotoxin, but were greatly inhibited in the presence of the sodium (Na+)-K+
      adenosine triphosphatase (ATPase) inhibitor ouabain. Incubation of tissues with
      TJ-17 and TJ-23 dose dependently increased ouabain-sensitive 86Rb uptake. The
      results of the study suggest that both Gorei-San and Toki-Shakuyaku-San reduce
      airway smooth muscle tone via a postjunctional mechanism probably through
      stimulation of the sodium pump and the subsequent
      hyperpolarization/repolarization of the cell membrane. These effects may
      contribute to the antiasthmatic properties of these herbal medicines.

PMID- 11292118
TI  - Comparison of functional efficacy of surfactant protein B analogues in lavaged
      rats.
AB  - Leakage of plasma proteins into the alveoli inhibits pulmonary surfactant
      function and worsens respiratory failure. Surfactant protein B (SP-B), is
      essential for surfactant function, but the N-terminal domain of human SP-B
      (residues 1.25, SP-B1-25) can mimic the biophysical properties of full length SP
      B1-78 in vitro. The authors compared the function and inhibition resistance of
      synthetic surfactant preparations containing SP-B analogues to a natural bovine
      surfactant preparation "Survanta". Eight groups of eight rats were lavaged to
      induce surfactant deficiency, fibrinogen was instilled as a surfactant inhibitor,
      and then they were rescued with exogenous surfactant. Five experimental
      surfactants were formulated by mixing 3% SP-B1-78, or an equimolar amount of SP
      B1-25 and/or 1% palmitoylated surfactant protein C (SP-C)1-35, into a standard
      phospholipid (PL) mixture: B1-78, B1-25, C1-35, B1-78+C1-35, and B1-25+C1-35
      surfactant preparations. Survanta was used as a positive control and PL and no
      treatment as a negative control. Lung function was assessed during a 2-h period
      using arterial blood gas and lung compliance measurements. Rats treated with B1
      25+C1-35 surfactant and Survanta maintained the highest oxygenation and lung
      compliance values throughout the experiments. The surfactants could be ranked as
      B1-25+C1-35 surfactant and Survanta >B1-25 and B1-78+C1-35 surfactants >others.
      Because the N-terminal domain of surfactant protein B1-25 can improve inhibition
      resistance, it may be able to substitute for surfactant protein B in exogenous
      surfactant preparations.

PMID- 11292119
TI  - Assessment of the viscosity of the pulmonary artery wall.
AB  - Large artery wall viscosity reduces the efficiency of heart/vessel coupling. The
      aim of the present study was to assess pulmonary artery wall viscosity through
      comparison of the static (Dst) and dynamic distensibility (Ddyn) of the vessel
      wall. Right pulmonary artery pressure and diameter was measured in 13 patients
      and eight healthy volunteers. Ddyn was calculated as the relative change in end
      diastolic diameter induced by the pressure pulse, and Dst as the relative change
      in mean diameter induced by the change in mean pressure during steady-state
      exercise. Dst did not differ significantly from Ddyn (mean+/-SD 22.8+/-19.2
      versus 21.0+/-18.3 10(-3) mmHg(-1)), as tested by paired t-test and analysis of
      covariance, with age as covariant. End-diastolic diameter increased, whereas Dst
      and Ddyn decreased as a function of age (r=-0.69 and -0.67, respectively; p<0.01
      for both). Ddyn did not change from rest to exercise in spite of a 23+/-16-beats
      min(-1) increase in cardiac frequency. Pulmonary artery wall viscosity was
      negligible and no increase in wall viscosity occurred during cardioacceleration.

PMID- 11292120
TI  - Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in
      children with wheezing.
AB  - In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae
      in reactive airway disease, 71 children aged 2-14 yrs with an acute episode of
      wheezing and 80 age-matched healthy children were studied. Sera for the
      determination of specific antibody levels and nasopharyngeal aspirates for the
      detection of M. pneumoniae and C. pneumoniae deoxyribonucleic acid were obtained
      on admission and after 4-6 weeks. All children with wheezing received a standard
      therapy with inhaled corticosteroids and bronchodilators for 5-7 days; when
      antibiotic was added on the basis of the judgement of the paediatrician in
      charge, clarithromycin 15 mg.kg body weight(-1).day(-1) for 10 days was used.
      Acute M. pneumoniae and C. pneumoniae infections were detected significantly more
      often in children with wheezing than in controls. In patients infected with one
      of the two pathogens, a history of recurrent wheezing was significantly more
      frequent than in those without either infection. During a 3-month follow-up
      period, among nonantibiotic-treated children, those with acute M. pneumoniae
      and/or C. pneumoniae infection showed a significantly higher recurrence of
      wheezing than those without acute M. pneumoniae and/or C. pneumoniae infection
      (p=0.03). These results highlight the apparently significant relationship of
      Mycoplasma pneumoniae and Chlamydia pneumoniae with wheezing in children,
      particularly in subjects with a history of recurrent episodes, and the possible
      improvement in the course of reactive airway disease within paediatric patients
      with acute Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection.

PMID- 11292121
TI  - Absence of bacterial colonization of the airways after therapeutic rigid
      bronchoscopy without stenting.
AB  - Following airway stenting, bacterial colonization of the airways with potentially
      pathogenic micro-organisms occurs within 4 weeks after treatment in the majority
      of patients. The objective of this study was to prospectively investigate whether
      nonstenting therapeutic rigid bronchoscopy (using laser, cryotherapy, mechanical
      dilatation or debridement) is followed by airway colonization or infection.
      Protected specimen brush sampling of the central airways and quantitative culture
      were performed immediately prior to, and 4 weeks after nonstenting therapeutic
      rigid bronchoscopy in 20 consecutive patients with central airway lesions. Prior
      to therapeutic bronchoscopy, airway colonization/infection was present in nine of
      20 (45%) patients. In these nine patients, 10 different potential pathogens were
      identified: Streptococcus pneumoniae (four cases), Pseudomonas aeruginosa
      (three), Haemophilus influenzae (two), and Serratia marcescens (one). Eight of
      these nine patients had a history of postobstructive infections, of which three
      were currently being treated with antibiotics. Four weeks following therapeutic
      bronchoscopy, airway colonization/infection was present in five of 20 (25%)
      patients, each of whom had airway colonization/infection prior to bronchoscopy.
      In three of these five patients, the same organisms were found 4 weeks after
      bronchoscopy as at baseline bronchoscopy. In two of five patients new organisms
      were identified: one case of Streptococcus viridans and one case of Haemophilus
      parainfluenzae, both considered to be nonpathogens. In four of nine patients with
      airway colonization/infection prior to bronchoscopy, the airways were clear of
      micro-organisms after the procedure. The authors conclude that: 1) nonstenting
      therapeutic rigid bronchoscopy is not complicated by airway colonization or
      infection by new potential pathogens; and 2) therapeutic rigid bronchoscopy led
      to clearing of airway colonization/infection in almost half of the patients
      studied.

PMID- 11292122
TI  - Ventilator associated pneumonia: quality of nonbronchoscopic bronchoalveolar
      lavage sample affects diagnostic yield.
AB  - The importance of predefined criteria for acceptable samples of respiratory
      therapists obtained lower respiratory samples were studied, using a
      nonbronchoscopic bronchoalveolar lavage (BAL) protocol for ventilated patients in
      the intensive care unit. Therapists were instructed and asked to follow
      guidelines for obtaining samples. Over one year, 219 samples were obtained by
      respiratory therapists. Of these, 115 were considered to be adequate samples
      using the following criteria: 60 mL of instilled volume, at least 5 mL of fluid
      aspirated, specimens sent for semiquantitative culture, a differential cell count
      of <5% bronchial epithelial cells. Overall, 52 samples grew one or more pathogen
      at >10,000 colony forming units (cfu).mL(-1) of BAL. The most common pathogen was
      Staphylococcus aureus (S. aureus) (11 samples), although Gram-negative bacilli
      were the single pathogen in 21 specimens. Of the 115 acceptable samples, 40 (35%)
      grew > or =1 pathogen at >10,000 cfu.mL(-1). For the 80 not acceptable samples
      which were sent for appropriate culture, 12 (15%) grew >10,000 cfu.mL(-1) BAL.
      This difference was significant (Chi-squared=9.44, p<0.01). Nonbronchoscopic
      bronchoalveolar lavage can be safely performed by respiratory therapists'. The
      authors recommend that a protocol be used to evaluate the quality of a
      bronchoalveolar lavage sample in the same manner sputum samples are screened
      prior to interpretation.

PMID- 11292123
TI  - New immunological approaches and cytokine targets in asthma and allergy.
AB  - The aims of current asthma treatment are to suppress airway inflammation and
      control symptoms, and corticosteroids maintain a commanding position in this
      role. Steroids effectively suppress inflammation in the majority of patients but
      have little impact on the natural history of this disease. In severe asthmatics,
      corticosteroids may have relatively less beneficial effects. Recent advances in
      understanding the inflammatory and immunological mechanisms of asthma have
      indicated many potential therapeutic avenues that may prevent or reverse
      abnormalities that underlie asthma. As the roles of effector cells, and of
      signalling and adhesion molecules are better understood, the opportunities to
      inhibit or prevent the inflammatory cascade have increased. In addition, there
      have been advances in the synthesis of proteins, monoclonal antibodies and new
      small molecule chemical entities, which may provide valuable flexibility in the
      therapeutic approach to asthma. The novel immunological approaches include the
      prevention of T-cell activation, attempts to influence the balance of T-helper
      cell (Th) populations to inhibit or prevent Th2-derived cytokine expression, and
      the inhibition or blockade of the downstream actions of these cytokines such as
      effects on immunoglobulin-E and eosinophils. These approaches provide broad as
      well as highly specific targeting, and also prospects for prevention and reversal
      of immunological and inflammatory abnormalities associated with asthma.
      Hopefully, the development of effective antiasthma agents with effects beyond
      those provided by current therapies coupled with lesser side-effects will further
      address the unmet needs of asthma.

PMID- 11292124
TI  - Noninvasive methods to measure airway inflammation: future considerations.
AB  - This last contribution to the series focuses on open questions regarding: 1)
      methodological issues; and 2) the potential clinical application of the
      noninvasive methods such as induced sputum and the analysis of exhaled air for
      the assessment of airway inflammation. In addition their potential future role in
      occupational health and the early diagnosis of neoplastic lesions are briefly
      discussed. The future clinical application of noninvasive methods will depend on
      the progress made to improve their practicability, particularly in rendering them
      less time consuming and cheaper. To assess their clinical value, prospective
      studies are needed to establish whether patients actually benefit from the
      results obtained. This is also important to implement the methods into the
      healthcare system and to obtain adequate financial compensation. Therefore, it is
      necessary to know: 1) whether the assessment of airwav inflammation can aid in
      coming to an earlier and better defined diagnosis; 2) whether by repeated
      monitoring it is possible to avoid exacerbations through earlier interventions;
      and 3) whether the long-term outcome of patients is improved through knowledge of
      the type and degree of airway inflammation that is taken into account in
      selecting the appropriate treatment. In the meantime a wealth of data has become
      available, both for induced sputum and the analysis of exhaled air, which give
      these methods the potential to be incorporated into future clinical practice.
      This, however, will, amongst the other issues, depend on favourable cost-benefit
      ratios which should also be the subject of future prospective studies.

PMID- 11292125
TI  - Tidal breath analysis for infant pulmonary function testing. ERS/ATS Task Force
      on Standards for Infant Respiratory Function Testing. European Respiratory
      Society/American Thoracic Society.
AB  - The aim of this position paper is to provide recommendations pertaining to
      software and equipment requirements when analysing tidal breathing measurements
      in infants. These guidelines cover numerous aspects including terminology and
      definitions, equipment, data acquisition and analysis, and reporting of results,
      and highlight areas in which further research is needed before consensus can be
      reached. When collecting tidal breathing data in infants and children, equipment
      dead space and resistance must be minimized, all sources of leak eliminated, and
      a flowmeter with appropriate frequency response and linearity employed. Inspired
      gases should be corrected to body temperature, barometric pressure and saturated
      with water vapour conditions and efforts made to eliminate the various sources of
      drift in volume that can occur. In addition, the analogue-to-digital converter
      used to sample data must be capable of adequately resolving the highest and
      lowest flows required by the study. An adequate sampling rate must be used; 50
      100 Hz may be sufficient for the determination of timing and volume parameters,
      especially in older infants, but rates of 200 Hz are recommended for analysis of
      the tidal breathing flow/volume loop and other sensitive parameters such as time
      to peak tidal expiratory flow/expiratory time. The potentially most troublesome
      aspect of tidal breath analysis from the computational point of view is the
      identification of the beginning and end of inspiration and expiration. Once
      methods and equipment for the measurement and analysis of tidal breathing in
      infants have been standardized, there is an urgent need to establish appropriate
      reference ranges for various key parameters so that they may be used more
      effectively in the clinical setting. Implementation of these recommendations
      should help to ensure that such measurements are as accurate as possible and that
      more meaningful comparisons can be made between data collected in different
      centres or with different equipment.

PMID- 11292126
TI  - Severity assessment in community-acquired pneumonia.
AB  - In current guidelines for the management of adults with community-acquired
      pneumonia (CAP), the triaging decision about hospitalization or intensive care
      unit (ICU) admission, and, as a consequence, selection of initial antimicrobial
      treatment is largely based on the assessment of pneumonia severity. The proposed
      severity criteria are mainly derived from studies determining predictors of
      adverse outcome. These include age, male sex, comorbidity, acute respiratory
      failure, severe sepsis and septic shock, extension of radiographic infiltrates,
      bacteraemia and CAP through several different pathogens such as Streptococcus
      pneumoniae, Staphylococcus aureus, Gram-negative enteric bacilli (GNEB), and
      signs of disease progression within the first 48-72 h. In addition, prediction
      rules and need for a complicated course in ambulatory and hospitalized patients,
      for the individual risk of death have been developed which may be helpful in
      determining the patient who might require hospitalization or intensive care,
      respectively. Risk classifications such as the scores developed by FINE et al.
      [40] are not only useful for identifying low risk patients who might safely be
      treated as outpatients, but apparently they will also play a major role in the
      evaluation of processes and outcomes of care for patients with CAP. Recent
      investigations have provided objective criteria for the definition of severe CAP
      requiring ICU admission. Whether the detection of infiltrates in the chest
      radiographs of patients with acute lower respiratory tract infection (LRTI)
      suggestive of mild pneumonia has an independent prognostic impact which
      fundamentally affects the concept of mild LRTI remains to be seen. Based on
      objective criteria for severity assessment it will be possible to define
      interventions aimed at reducing hospital admission rates, define a risk-adapted
      antimicrobial treatment regimen, reduce costs for antimicrobial treatment and
      supportive measures, shorten hospital stay, and, thereby, improve the quality of
      care for patients with community-acquired pneumonia.

PMID- 11292127
TI  - Primary pulmonary artery sarcoma resembling chronic thromboembolic pulmonary
      disease.
AB  - Two cases of primary pulmonary artery sarcoma resembling chronic thromboembolic
      disease features are presented. Tumour identification was achieved after
      pulmonarv thromboendarterectomy, which was indicated by documentation of a
      prothrombotic state in both patients. A doubtful history of pulmonary emboli or
      deep venous thrombosis should alert medical personnel to the possible presence of
      a primary pulmonary artery sarcoma. Advanced imaging methods such as gadolinium
      enhanced magnetic resonance imaging could be useful in considering pulmonary
      thromboendarterectomy. If a tumour is detected, its surgical resection should be
      considered with caution, taking into account the poor survival results. Invasion
      of the adventitia or the right ventricle, as documented in the present cases, is
      unusual. As far as the present authors know, this is the first report of this
      kind of tumour and its coexistence with an activated protein C resistance state
      and type II heparin-induced thrombocytopenia.

PMID- 11292128
TI  - Severe obstructive sleep apnoea secondary to pressure garments used in the
      treatment of hypertrophic burn scars.
AB  - Obstructive sleep apnoea (OSA) secondary to pressure garments used to treat
      hypertrophic scarring of burns has never been reported. The present study
      describes two children who presented with OSA following introduction of such
      garments for management of hypertrophic scars following severe facial and upper
      body burns. Complex sleep polysomnography confirmed severe OSA with desaturations
      sufficient to result in physiological dysfunction that significantly improved on
      removal of the garments. As there is little evidence to suggest that the use of
      such garments alters the end result, the potentially serious side effect of
      obstructive sleep apnoea should be considered before their use is advised.

PMID- 11292129
TI  - Validation of assays for inflammatory mediators in sputum.

PMID- 11292130
TI  - Radiotherapy: cost, access and quality--which way should we go?

PMID- 11292131
TI  - A tool to measure radiotherapy complexity and workload: derivation from the basic
      treatment equivalent (BTE) concept.
AB  - Radiotherapy workload is poorly represented by simple parameters of patients,
      fractions or fields treated because these do not contain any measure of treatment
      complexity. However, complexity is increasing and there is an urgent need to
      quantify this. We have evaluated the basic treatment equivalent (BTE) model as a
      measure of radiotherapy workload and complexity. Radiotherapy treatment times,
      from the patient entering to exiting the treatment room maze, were measured for
      1298 treatment sessions on 269 patients. The data were used to assess the
      original model and derive three new models for predicting treatment duration. The
      most complicated, the 'Addenbrooke's complex model', contained two additional
      predictor variables, including 'site/technique', in a linear additive form.
      Before the study, the department used a standard treatment appointment time of 10
      minutes. However, 50% of the measured treatments took longer than 10 minutes,
      (mean 10.9). Summed over the working day, this discrepancy indicates that a
      standard 10-minute appointment is a poor basis for scheduling radiotherapy. The
      original BTE model was effective in predicting treatment times, although this was
      improved by refinement of the model. The Addenbrooke's complex model correctly
      predicted 70% of treatment times to within 2 minutes (55% for the original BTE
      model), 80% to within 2.5 minutes and 95% to within 4.7 minutes. The percentage
      of the variation in observed times accounted for by the model is 59.4%. The
      models can represent radiotherapy complexity, can improve scheduling on linear
      accelerators, and are likely to be applicable to other departments. They are thus
      tools to assess the impact of changes in complexity from new techniques, trial
      protocols (e.g. the Medical Research Council prostate radiotherapy trial RTO1),
      and possible time saving from advanced technology such as multileaf collimators
      (MLCs) or automated machine set-up. The replacement of manually-lifted shielding
      blocks by MLCs should save 1.1-1.5 minutes for a three- or four-field pelvic plan
      (i.e. 12%-13%). The models could also be used to aid planning for future linear
      accelerator provision and for costing radiotherapy treatment.

PMID- 11292132
TI  - How much surplus capacity is required to maintain low waiting times?
AB  - Random fluctuations in demand make it impossible to see all patients in a very
      short time scale unless capacity exceeds the mean demand. We describe a model to
      estimate the capacity levels required as a function of mean demand. Random
      fluctuations were assumed to follow a Poisson distribution. A Monte Carlo
      analysis was used to model variations in length of waiting times. To see patients
      without a waiting list the capacity must exceed mean demand by an amount
      proportional to the square root of the mean; if capacity equals mean demand, then
      actual demand will exceed capacity almost half the time. The smaller the mean
      demand, the greater the percentage increase in capacity that is required. Thus,
      subdivision of numbers, for subspecialization or fast-tracking, demands greater
      overall capacity. When multiple serial steps are required, each step must have
      spare capacity if a waiting list is to be avoided. When capacity is only slightly
      greater than mean demand, random fluctuations mean that targets can be met for
      long stretches of time, but these are interspersed with periods when the waiting
      list rises substantially. Allowing a small waiting time (2-4 weeks) considerably
      reduces the excess capacity required. Targets such as the 2-week wait for cancer
      referrals can be achieved only if resource levels are set to give considerably
      more patient slots per week than mean demand. The level of spare capacity
      required depends on the level of demand and the maximum waiting time permitted.
      Without surplus capacity, waiting targets cannot be met. To meet the 2-week
      waiting target, capacity must exceed mean demand by two patient slots per week
      for 99% success, or by one slot per week for 90% success.

PMID- 11292133
TI  - Radiotherapy service delivery models for a dispersed patient population.
AB  - Access to health care interventions can be impeded when significant patient
      travel is required. In this economic evaluation we compare, from a societal
      perspective, three scenarios for the delivery of radiation treatment to an
      idealized population of 1,600 patients distributed between two urban nodes (1,200
      + 400 patients each) separated by up to 500 km. As it is implicitly assumed that
      the clinical outcome for those patients who access the system is independent of
      the service delivery model, this study constitutes a cost minimization analysis
      from a societal perspective. The costs to the health care system are based on an
      activity costing model developed by us and consistent with recent Canadian
      studies. The costs to the patient are approximated by a formula that includes
      direct costs (travel and accommodation) and indirect (time) costs, with the
      latter based on a human capital approach. A sensitivity analysis has been
      performed to confirm the robustness of our conclusions both to uncertainties in
      the input data and to the inclusion of time costs, the estimation of which
      remains controversial. From a societal cost perspective only, we show that
      outreach radiotherapy (central comprehensive facility and satellite) is the
      economically superior service delivery model for separations between 30 km and
      170 km. Beyond 170 km, a fully decentralized service would be warranted if the
      only consideration were societal economic advantage.

PMID- 11292134
TI  - Improving patient recruitment to multicentre clinical trials: the case for
      employing a data manager in a district general hospital-based oncology centre.
AB  - One of the most frequently cited reasons for poor recruitment to multicentre
      randomized clinical trials is the additional workload placed on clinical staff.
      We report the effect on patient recruitment of employing a data manager to
      support clinical staff in an English district general hospital (DGH). In
      addition, we explore the effect data managers have on the quality of data
      collected, proxied by the number of queries arising with the trial organizers. We
      estimate that the cost of employing a data manager on a full-time basis is 502
      per patient recruited but may amount to 326 if the appointment is part-time. Data
      quality is high when full responsibility lies with a data manager but falls when
      responsibility is shared. Whether the costs of employing a data manager to
      recruit patients from a DGH are worth incurring depends on the value placed on
      the speed at which multicentre trials can be completed, how important it is to
      broaden the research base beyond the traditional setting of teaching hospitals,
      and the amount of evaluative data required.

PMID- 11292135
TI  - Where now with training in clinical oncology?

PMID- 11292136
TI  - Portfolio learning with cancer patients: an integrated module in undergraduate
      medical education.
AB  - A model of undergraduate education based on a one to one relationship between a
      student and a patient with cancer has become a core module within the University
      of Wales College of Medicine undergraduate curriculum. The project combines the
      powerful impact of a one to one interaction with an active investigative and
      reflective approach to issues triggered from that patient's cancer journey. The
      aim is to provide each medical student with an understanding of the impact of a
      malignant disease and its treatment on patients and their families through the
      experience of one patient with cancer. The benefits of the project cover the
      areas of attitudes, skills and knowledge. Students are assessed on their
      involvement with the patient, in tutorials and on their portfolio, in which they
      record all aspects of the project. Student evaluations indicate high levels of
      appreciation of the project, despite its potentially strong emotional content.

PMID- 11292137
TI  - Dermatomyositis in association with transitional cell carcinoma of the bladder.
AB  - There is a well-recognized association between the inflammatory dermatomyopathy,
      dermatomyositis, and underlying visceral malignancy in adults. It is most
      commonly found in association with malignancies arising in the lung, breast and
      stomach. We report a case found in association with transitional cell carcinoma
      of the bladder, a site where there have only been a handful of previous reports.

PMID- 11292138
TI  - Neurocutaneous melanosis: a case of primary intracranial melanoma with
      metastasis.
AB  - Neurocutaneous melanosis is a rare disorder characterized by the presence of
      large or multiple congenital melanocytic naevi and benign or malignant pigment
      cell tumours of the leptomeninges. Distant metastasis is unusual in primary
      leptomeningeal/intracranial melanomas. We present the case history of an adult
      male who had multiple primary intracranial melanomas associated with
      neurocutaneous melanosis (naevus of Ota) in the ophthalmic division of the left
      trigeminal nerve. Excision of the intracranial tumours was carried out in two
      stages, but the patient died 2 days after the second operation. Autopsy showed
      multiple metastatic deposits in the liver. Symptoms and signs of raised
      intracranial pressure, the presence of Ota's naevus, and a dural-based mass or
      masses should alert the treating physician to suspect a primary
      leptomeningeal/intracranial melanoma.

PMID- 11292139
TI  - Radiation recall with oxaliplatin: report of a case and a review of the
      literature.
AB  - Oxaliplatin is a new platinum derivative that has significant activity in
      patients with metastatic colorectal carcinoma. Some of these patients may have
      been previously treated with radiotherapy. The interaction of radiotherapy with
      oxaliplatin needs to be further studied. We report a patient with advanced
      colonic carcinoma who was treated with concomitant chemoirradiation with
      oxaliplatin and developed a peculiar dermnatitis in the irradiated field after
      being exposed to subsequent chemotherapy with oxaliplatin.

PMID- 11292140
TI  - United Kingdom Children's Cancer Study Group (UKCCSG) radiotherapy and brain
      tumour groups: medulloblastoma/PNET and craniospinal radiotherapy (CSRT): report
      of a workshop held in Leeds, 30 June 1999.
AB  - Primitive neuroectodermal tumours (PNET), of which cerebellar medulloblastoma is
      the most frequent, are embryonal central nervous system tumours arising mainly in
      children. They are characterized by their propensity for metastasis via the
      cerebrospinal fluid. They are radiosensitive and craniospinal radiotherapy (CSRT)
      is an important part of their management. This is a complex radiotherapy (RT)
      technique, the accuracy of which contributes to the survival and quality of
      survival of treated children. In the last 25 years, European and North American
      collaborative studies have investigated the role of adjuvant chemotherapy. The
      planning and delivery of CSRT have to be of the highest quality. It is important
      to incorporate all modern technical RT developments into CSRT. It is possible
      that optimizing fractionation may further improve outcome. The purpose of this
      workshop was to review the current status of CSRT planning and administration in
      the light of RT developments. Current results of the treatement of
      medulloblastoma and PNET were reviewed and UK involvement in possible future
      collaborative trials was discussed.

PMID- 11292141
TI  - User involvement in cancer services.

PMID- 11292142
TI  - Adenocarcinoma of the gall bladder presenting with haematuria.

PMID- 11292144
TI  - The use of the Australian Basic Treatment Equivalent (BTE) workload measure for
      linear accelerators in Canada.
AB  - The Inter Society of Radiation Oncologists of North America (ISRON) workload
      standard for linear accelerators is the one most widely used; it regards the
      treatment of 250 or more patients per year as an acceptable limit. Nevertheless,
      there is concern that this standard does not represent the current workload of
      linear accelerators, given that the complexity of techniques and equipment has
      increased significantly since the ISRON model was developed in the late 1980s.
      Delaney et al. recently validated a workload indicator for Australian (AUS)
      centres, known as the basic treatment equivalent (BTE). They showed that this was
      a better predictor of workload and that there was less variation between centres
      using this model than there would have been by using fields/hour. This centre
      attempted to validate this model for use in a Canadian centre, by collecting
      treatment data on all linear accelerator-treated patients during February 1998.
      The linear accelerators at this centre delivered 2,295 fractions (6,928 fields)
      in 662 hours during February 1998. When 15 minutes was used as a denominator, the
      BTE model functioned as a better workload indicator than simple measures such as
      fields/hour. It also had better performance in reducing variability between
      machines. A BTE of 3,403 was calculated for these machines. The mean value for
      fields/hour, BTE/hour and BTE/fraction for this centre fell within the range of
      values quoted by AUS centres. The BTE/fraction value for this centre was
      relatively high compared with the AUS mean, indicating this centre's reliance on
      the use of a high number of complex techniques. We recommend that the model
      should be further refined for the Canadian context by developing BTE values with
      the use of local time and motion studies, including factors such as multileaf
      collimators and enhanced dynamic wedges.

PMID- 11292143
TI  - Adjuvant chemotherapy for gastro-oesophageal cancer with epirubicin, cisplatin
      and fluorouracil: a single-centre experience.

PMID- 11292145
TI  - Supportive ventilation on a geriatric ward: better, but is it the best?

PMID- 11292146
TI  - The influence of social support and perceived control on handicap and quality of
      life after stroke.
AB  - It has been suggested that external factors, such as perceived control of life
      and social support, influence the interactions of impairment, disability and
      handicap in the WHO model. Therefore, we assessed the effect of these two factors
      on the relationships between disability, handicap and quality of life in patients
      recovering from stroke. One hundred individuals, retrospectively and randomly
      selected from participants in an inpatient stroke rehabilitation program, were
      tested one year after discharge, using the Functional Independence Measure, the
      London Handicap Scale, the Life Satisfaction Assessment, the Tel-Aviv Social
      Support Instrument, and the Perceived Stress Scale. Impairment, disability,
      handicap and quality of life after stroke correlated positively and significantly
      with each other. Significant moderation of the influence that disability exerts
      on handicap was affected by perception of control, and by the influence of
      handicap over quality of life by social support. Thus, external factors can cause
      inconsistent interactions between components of the WHO model. Patient outcome
      may be improved if such factors are considered.

PMID- 11292147
TI  - Differences in gait parameters at a preferred walking speed in healthy subjects
      due to age, height and body weight.
AB  - The objective of our cross-sectional study was to investigate the changes
      associated with age and gender in walking speed, stride length and cadence of
      healthy women and men over the adult age range, and establish the effects of
      anthropometric indices such as height and body weight. We examined 118 women and
      121 men (age range, 19-90 years). Subjects walked at their preferred speed over a
      12-meter walkway crossing two Kistler force plates: cadence was calculated from
      heel strike times recorded from the Kistler force plates; walking speed was
      measured using an infrared reflecting system; and stride length was calculated
      from the walking speed and cadence. Older healthy subjects had lower values for
      walking speed and stride length than younger subjects. While there is little
      difference in the percentage reduction between women and men over the adult age
      range. the absolute values for walking speed are lower in women than men at all
      ages. In women, the percentage of explained variance for decline in walking speed
      was 30%, and for decline in stride length 400%. If body weight was also taken
      into account, the percentage of explained variance for walking speed was 37%, and
      for stride length 59%. A similar calculation for men yields 34% for decline in
      walking speed, and 42% for decline in stride length. Cadence was not associated
      with age, height and body weight. The standard errors for the estimates of
      walking speed in both women and men, respectively, are reduced by 8% and 3% using
      the multiple regression technique. The corresponding standard errors for stride
      length were reduced by, respectively, 19% and 13% if height in either sexes, or
      height and body weight in women, were taken into account. In conclusion,
      preferred walking speed and stride length decline with age in healthy people.
      Lower values found in old healthy subjects partly contributed to the difference
      in height and body weight between old and young subjects. Cadence was not
      correlated with age, height and body weight.

PMID- 11292148
TI  - The validity of informant report for grading the severity of Alzheimer's
      dementia.
AB  - The validity of informant-based techniques has been established for the detection
      of dementia cases by non-pathological individuals, but is still controversial for
      the assessment of the severity of dementia. This study aimed at ascertaining
      whether informant-based evaluation (the so-called informant report) of the
      cognitive and behavioral impairment of a patient is valid for grading the
      severity of dementia, and consistent with objective assessment of the patient's
      cognitive and behavioral functioning. We enrolled 96 community-dwelling
      outpatients and 56 controls assessed at the Geriatric Evaluation Unit of the
      University of Modena, Italy. All patients scored lower than 27 on the MMSE, and
      met DSM-IV inclusion criteria for Alzheimer's dementia. Patients and controls
      were administered the CAMDEX interview, containing a section which collects
      participant (patient or control) and informant evaluations on dementia-related
      cognitive and behavioral deficits. The informant report resulted effective at
      MANOVA for grading the severity of dementia in 4 of its 5 measures (namely,
      memory, everyday activities, general mental functioning and depressed mood), and
      was correlated with the scores of several scales of the CAMDEX cognitive section
      (i.e., CAMCOG). Instead, the participant's (patient or control) report showed a
      lower capacity for grading dementia, and was poorly correlated with the
      psychometric outcomes of cognitive functioning. On the whole, the results
      corroborated the validity of the informant report in the diagnostic work-up for
      grading dementia, given its sensitivity to the severity of dementia, and its
      consistency with cognitive psychometric outcomes.

PMID- 11292149
TI  - Predictors of two-year mortality in older nursing home residents. The IRA study.
      Istituto di Riposo per Anziani.
AB  - Besides functional impairment, several factors have been associated with
      mortality in institutionalized older subjects, including advanced age, gender,
      comorbidity, and malnutrition. We investigated the possible association of a
      large number of factors, including functional, anthropometric, nutritional,
      metabolic, clinical, and demographic variables, with two-year all-cause mortality
      in a sample of 344 institutionalized older subjects (> or = 65 years) without
      evidence of acute illness at the time of observation. Although a number of
      factors were associated with mortality risk, multivariate analysis showed that
      only severe disability (6 vs 0-1 lost ADL, O.R.: 3.37, C.I. 95%: 1.76-7.3) and
      low albumin levels (lowest vs highest tertile: O.R.: 3.0, C.I. 95%: 1.65-5.43)
      were independent predictors of outcome. Moreover, in the analysis stratified for
      degree of disability and albumin tertiles, we found a strong gradient in
      mortality risk with increasing disability and decreasing albumin levels. These
      results further support the value of these two simple parameters in identifying
      frail institutionalized older individuals.

PMID- 11292150
TI  - Disparate effects of socioeconomic status on physical function and emotional well
      being in older adults.
AB  - We tested the hypothesis that among community living older adults with relatively
      low and high socioeconomic status (SES), low SES is associated with both poorer
      emotional well-being and physical function. Ambulatory, community living older
      men and women (70-89 years of age) were recruited from outpatient geriatric
      assessment clinics in relatively high socioeconomic areas of greater Boston (High
      SES, N=47), and from an urban senior center in the inner city (Low SES, N=66). We
      assessed health status, mental health, upper and lower extremity strength and
      physical function. We found that health status was not significantly different in
      the two groups. Quadriceps strength (Low SES: 199+/-57 N; High SES: 190+/-56 N;
      p=0.531) and Up and Go times (Low SES: 14.3+/-3.1 sec; High SES: 16.7+/-9.5 sec;
      p=0.068) were not significantly different in the two groups, while grip strength
      was slightly higher in the Low SES group (Low SES: 22.8+/-6.45 kg; High SES:
      20.07+/-7.55 kg; p=0.049). In contrast, subjects with Low SES tended to have an
      increased tendency towards depression. Scores on the Geriatric Depression Scale
      were 3.8+/-3.0 in Low SES, and 1.8+/-2.8 in High SES (p<0.001). We conclude that
      while health status and physical function were not worse in subjects with low
      SES, emotional well-being was markedly less compared to seniors with high SES.
      SES may have disparate effects on physical function and mental health, perhaps
      due to different compensatory mechanisms.

PMID- 11292151
TI  - Immunogenicity and safety of three commercial influenza vaccines in
      institutionalized elderly.
AB  - Influenza is a leading cause of morbidity and mortality in elderly people. This
      prospective, observed-blind, randomized, multicenter trial compares the
      immunogenicity and safety of three influenza vaccines in a sample of 635 elderly
      residents of four nursing homes in Milano (Italy). All vaccines were well
      tolerated: no serious adverse events were recorded, and a small number (9
      subjects) of local and systemic reactions were observed. Twenty-nine
      oropharyngeal swabs were taken during the season from ILI (influenza-like
      illness) patients, none of whom was positive for influenza and other respiratory
      viruses. Immunogenicity was evaluated in a subgroup of 111 subjects with blood
      samples obtained just before vaccination and after 4 and 12 weeks. The adjuvanted
      vaccines, subunit vaccine with MF59 (a-SUV) and virosome subunit vaccine (v-SUV),
      induced a higher antibody response than whole virus vaccine (WVV). There was no
      significant difference between groups that received a-SUV and v-SUV, but the a
      SUV group had higher values of geometric mean titres than the v-SUV group for
      H1N1 and B influenza strains. These findings suggest that influenza vaccination
      is effective, and they underscore the importance of vaccination programs for
      institutionalized elderly. Further studies are needed to compare other adjuvanted
      vaccines in order to define their different properties.

PMID- 11292152
TI  - Impact of pain on recreational activities of nursing home residents.
AB  - The high prevalence of pain in older adults in nursing homes and long-term care
      institutions is a challenging problem. Nursing home residents were questioned to
      evaluate whether pain might be an obstacle to their active participation in
      recreational activities, especially physical activities. This study shows that
      the intensity and daily experience of pain are both obstacles to participation in
      physical activities, especially in the oldest patients. The findings also show
      that participation is linked to the autonomy of the patient; more information
      about the benefits of physical activity, and coordinating efforts in this area
      are needed in order to help the elderly preserve their autonomy and quality of
      life.

PMID- 11292153
TI  - Predicting length of stay of older patients with exacerbated chronic obstructive
      pulmonary disease.
AB  - Our study objective was to identify factors predicting length of hospital stay of
      older patients with exacerbated chronic obstructive pulmonary disease (COPD)
      through a multicenter, cross-sectional, retrospective study. We examined 3789
      patients aged 74.3+/-11.1 years (mean+/-SD), 66.1% males, consecutively
      hospitalized in 32 wards of General Medicine and 31 of Geriatrics in acute care
      hospitals for exacerbated COPD in 10 bimonthly periods between 1988 and 1997. On
      admission, patients underwent a structured assessment of demographic data,
      nutritional status, cognitive and physical functions, comorbidity, and
      pharmacological therapy in the two weeks prior to admission. Patients were
      grouped according to whether their length of stay exceeded or not the 75th
      percentile of stay distribution in each bimonthly period. Variables univariately
      distinguishing groups were entered into a logistic regression analysis having
      long-stay as the dependent variable. Living alone (Odds Ratio 1.33, 95%
      Confidence Limits 1.03-1.70), use of more than 3 drugs prior to admission (OR
      1.29, CL 1.09-1.51), use of drugs with respiratory depressant properties prior to
      admission (OR 1.24, CL 1.05-1.46), and the presence of more than 3 comorbid
      diseases (OR 1.88, CL 1.61-2.19) were independent correlates of long-stay. Age
      did not predict length of stay. In conclusion, selected health outcomes and
      indicators of disease severity, but not age, target COPD patients at risk of long
      stay. Research is needed to verify whether these data can help program
      interventions aimed at shortening length of stay and, thus, at reducing annual
      hospitalization costs of the elderly.

PMID- 11292154
TI  - Non-invasive ventilation for frail elderly patients with acute respiratory
      failure.
AB  - We describe 3 elderly patients with acute respiratory failure who received
      respiratory assistance with nasal bi-level positive airway pressure (BiPAP) on
      the ward. In these patients with poor prognostic factors, non-invasive positive
      pressure ventilation was preferred as a reasonable alternative to invasive
      ventilation; indeed, their admission to the intensive care unit for mechanical
      support was considered inappropriate. Despite the small number of patients and
      limited experience with the technique, BiPAP is discussed here as a possible
      treatment for severe respiratory failure when endotracheal ventilation is
      controversial, especially in frail patients 80 years of age or older, because
      invasive ventilation is associated with high mortality and morbidity in these
      patients. Two questions nevertheless need further evaluation in this setting, and
      are also addressed. The first is technical: can transient non-invasive breathing
      assistance be delivered on the ward? The second is ethical: is BiPAP a possible
      alternative when invasive ventilation is considered inappropriate?

PMID- 11292155
TI  - Surgery of otosclerosis in the elderly.
AB  - Auditory results following stapes surgery in 26 patients with otosclerosis >60
      years of age at the time of surgery were compared with those obtained in 140
      patients <60 years undergoing stapes surgery during the same time period.
      Stapedotomy was performed in all cases. The mean follow-up period was 29 months.
      Hearing results as judged by postoperative air-bone gaps were as good in the
      older age group as in the younger patients. Moreover, complications of surgery,
      such as postoperative formation of perilymphatic fistula, did not occur more
      frequently in elderly vs younger patients. On the basis of the results obtained,
      it is concluded that stapes surgery should be offered to elderly patients with
      the same indications as younger patients with otosclerosis.

PMID- 11292156
TI  - Manual asymmetries in reaching movement control. I: Study of right-handers.
AB  - Two experiments investigated manual asymmetries in the control of rapid reaching
      movements according to the movement parameters to be controlled. Single- and
      double-step reaching movements were performed by right-handed subjects with both
      hands. Pro and retroactive processes involved in rapid movement control were
      investigated. Manual performances and kinematic properties of hand movements
      showed that various forms of hemispheric specialization were involved in sensori
      motor information processing. It was shown that the effects of hemispheric
      specialization were specific to the task constraints, that is, to the various
      operations involved in movement control.

PMID- 11292157
TI  - The contribution of functional neuroimaging to recovery after brain damage: a
      review.
AB  - The introduction of functional neuroimaging techniques has contributed to
      understanding the neural correlates of recovery of motor, sensory and cognitive
      functions after brain damage. In this paper, we review the literature of the past
      twenty years, with particular emphasis on quantitative studies of cerebral blood
      flow and metabolism. Studies are presented that examine recovery from
      hemiparesis, aphasia, spatial hemineglect and sensory disorders. The contribution
      of this research is critically discussed in a methodological perspective. A basic
      distinction is made between cerebral plasticity and recovery of functions. It is
      also argued that the most frequently used experimental designs do not permit
      directly relating changes in brain activity to functional recovery. The
      importance of accurate behavioural measures is underlined. Alternative
      experimental designs are proposed, based on correlations between behavioural
      performance and brain activations.

PMID- 11292158
TI  - Manual asymmetries in reaching movement control. II: Study of left-handers.
AB  - Two experiments performed with left-handed subjects investigated how the manual
      asymmetries and hemispheric specialization involved in visuo-manual coordination
      are associated with handedness. Pro and retroactive processes involved in rapid
      movement control were analyzed according to the different movement parameters to
      be controlled, similar to studies performed with right-handers (Boulinguez,
      Nougier and Velay, 2001). Manual performances and kinematic properties of
      reaching movements showed that the left and right hands of left-handers behaved
      in the same way as the left and right hands of right-handers. Results are
      discussed in the light of the independence of handedness and other forms of
      cerebral dominance in sensori-motor information processing involved in hand
      movements.

PMID- 11292159
TI  - Generalized auditory agnosia with spared music recognition in a left-hander.
      Analysis of a case with a right temporal stroke.
AB  - After a right temporoparietal stroke, a left-handed man lost the ability to
      understand speech and environmental sounds but developed greater appreciation for
      music. The patient had preserved reading and writing but poor verbal
      comprehension. Slower speech, single syllable words, and minimal written cues
      greatly facilitated his verbal comprehension. On identifying environmental
      sounds, he made predominant acoustic errors. Although he failed to name melodies,
      he could match, describe, and sing them. The patient had normal hearing except
      for presbyacusis, right-ear dominance for phonemes, and normal discrimination of
      basic psychoacoustic features and rhythm. Further testing disclosed difficulty
      distinguishing tone sequences and discriminating two clicks and short-versus-long
      tones, particularly in the left ear. Together, these findings suggest impairment
      in a direct route for temporal analysis and auditory word forms in his right
      hemisphere to Wernicke's area in his left hemisphere. The findings further
      suggest a separate and possibly rhythm-based mechanism for music recognition.

PMID- 11292160
TI  - When ottoman is easier than chair: an inverse frequency effect in jargon aphasia.
AB  - This paper presents evidence of an inverse frequency effect in jargon aphasia.
      The subject (JP) showed a pre-disposition for low frequency word production on a
      range of tasks, including picture naming, sentence completion and naming in
      categories. Her real word errors were also striking, in that these tended to be
      lower in frequency than the target. Reading data suggested that the inverse
      frequency effect was present only when production was semantically mediated. It
      was therefore hypothesised that the effect was at least partly due to the
      semantic characteristics of low frequency items. Some support for this was
      obtained from a comprehension task showing that JP's understanding of low
      frequency terms, which she often produced as errors, was superior to her
      understanding of high frequency terms. Possible explanations for these findings
      are considered.

PMID- 11292161
TI  - The hippocampal contribution to verbal fluency in patients with temporal lobe
      epilepsy.
AB  - We report the effects of hippocampal and non-hippocampal temporal-lobe
      dysfunction on verbal fluency performance. Quantitative aspects of semantic and
      phonemic fluency performance were examined in 46 patients with right- or left
      temporal-lobe epilepsy and 20 healthy controls. A pattern of fewer words
      generated on semantic rather than phonemic fluency tasks was found among patients
      with damage to hippocampal structures. This pattern was not obtained in patients
      with non-hippocampal temporal-lobe damage, suggesting that the hippocampus plays
      a crucial role in semantic fluency performance. An interesting lateralization
      effect was obtained. Among patients with left temporal-lobe involvement, fluency
      performance was impaired regardless of whether the hippocampus was involved. In
      contrast, among patients with right temporal-lobe involvement, fluency
      performance was impaired only when the hippocampus was involved.

PMID- 11292162
TI  - Callosal transfer in different subtypes of developmental dyslexia.
AB  - Sixteen controls (age 6-13) and 20 native Italian children with developmental
      dyslexia (age 7-15) received a test of callosal transfer of tactile information.
      Among the dyslexic children, 7 had a diagnosis of L-type, 7 of P-type and 6 of M
      type dyslexia according to Bakker's classification. Both control children and
      children with dyslexia made a significantly larger number of errors in the
      crossed localization condition (implying callosal transfer of tactile
      information) vs. the uncrossed condition. In the same condition, children with
      dyslexia made a significantly larger number of errors than controls. In the
      crossed localization condition L-types and M-types made a significantly larger
      number of errors than P-types and controls, while there was no significant
      difference in performance between P-types and controls. These findings are
      discussed in terms of defective callosal transfer or deficient somatosensory
      representation in children with L- and M-dyslexia.

PMID- 11292163
TI  - Hemispheric asymmetry and interhemispheric transfer in pointing depend on the
      spatial components of the movement.
AB  - The purpose of the present study was to compare the asymmetry and transfer in 3
      pointing movements with increasing spatial requirements. The triggering signal
      was one of four visual targets appearing on the right or left of a central
      fixation point (FP). The first task consisted in simply removing the arm from the
      starting platform; the second was a pointing movement towards the FP, and the
      third was a classical pointing task towards one of the four lateral targets. 20
      right-handers (Rhrs) and 20 left-handers (Lhrs) participated in this experiment.
      In the classical pointing task (task 3), the reaction times were shorter in the
      Rhrs using their left hand. No such hand-related difference was observed in the
      Lhrs. No hand asymmetry was observed in the other tasks. In addition, the
      responses were faster in the uncrossed than in the crossed conditions, in task 3
      only. It was concluded that in pointing tasks, both the hemispheric asymmetry and
      the interhemispheric transfer depend on the spatial requirements of the movement.

PMID- 11292164
TI  - Prepubescent children show the adult relationship between dermatoglyphic
      asymmetry and performance on sexually dimorphic tasks.
AB  - The dermatoglyphic pattern of dermal ridges that constitutes the human
      fingerprint is complete by the 16th foetal week and its development is thought to
      be influenced by prenatal hormones. Finger ridge count (FRC) is asymmetrical with
      the majority having more ridges on the finger tips of the right hand (R >) while
      the minority have more on the left (L >). In adults, the R > condition has been
      associated with male-typical, and the L > condition with female-typical,
      performance on sexually dimorphic tasks. Here we report that 60 prepubescent
      children showed the same sex difference and the same relationship as adults
      between FRC and task performance: girls and L > children performed a female
      favouring task better while boys and R > children performed a male-favouring task
      better. This finding indicates that these sex-related task performance
      differences are not dependent on the activational effects of adult gonadal
      steroids. The implications of these findings for prenatal influences on
      neuropsychological development are discussed.

PMID- 11292165
TI  - Bcl-2 and Bax expression in cartilage and bone cells after high-dose
      corticosterone treatment in rats.
AB  - The expression of Bcl-2 and Bax has been evaluated by immunohistochemistry in
      normal rats, and in rats after treatment with high-dose corticosterone (CORT).
      Proliferative (PC) and maturative/hypertrophic (MaHC) chondrocytes of the growth
      plate have been examined, as well as osteoblasts (Obs), osteocytes (Ots) and
      osteoclasts (Ocs) of the metaphyseal secondary spongiosa. For each cell type, the
      Bcl-2 and Bax immunopositive cells were expressed as a percentage of the total
      number of cells. Bcl-2 and Bax expression was considered to be enhanced when the
      percentage of positive cells rose. Bcl-2 and Bax were expressed in all cell
      types, and two main kinds of labeling distribution, both suggestive of
      association with intracellular organelles, were observed in the cytoplasm: scarce
      and spotty labeling (type 1) or abundant, granular and diffuse labeling (type 2).
      In some cases, nuclear membranes could also be seen to be positive. Positive PCs
      and Obs generally showed a labeling of type 1, MaHCs and Ocs of type 2, while Ots
      varied with labeling of type 1 or type 2. CORT administration induced a fall in
      the percentage of Bcl-2 immunopositive cells, and a rise in that of Bax
      immunopositive cells, in PCs and Ots. The same trend was observed in MaHCs,
      although the Bcl-2 decrease was not significant. The percentage of Bcl-2 and Bax
      immunopositive Obs rose, and their labeling distribution shifted from type 1- to
      type 2-labeled cells. Ocs showed the highest immunopositivity for both Bcl-2 and
      Bax, which did not change after CORT administration. These data suggest that CORT
      treatment, by lowering Bcl-2, and raising Bax expression, may promote the
      apoptotic process in PCs, MaHCs and Ots. Obs, however, do not undergo the same
      variations. This finding, together with the results of a previous study showing
      that CORT administration raises the frequency of apoptotic Obs, does not support
      a direct relationship between apoptosis and Bax overexpression, at least in Obs.
      The CORT effect might be related to cell types and their state of
      differentiation, so that Bcl-2 and Bax might regulate not only the machinery of
      cell death, but also cell proliferation and differentiation.

PMID- 11292166
TI  - Expression and localization of immunoreactive-sialomucin complex (Muc4) in
      salivary glands.
AB  - Sialomucin Complex (SMC; Muc4) is a heterodimeric glycoprotein consisting of two
      subunits, the mucin component ASGP-1 and the transmembrane subunit ASGP-2.
      Northern blot and immunoblot analyses demonstrated the presence of SMC/Muc4 in
      submaxillary, sublingual and parotid salivary glands of the rat.
      Immunocytochemical staining of SMC using monoclonal antisera raised against ASGP
      2 and glycosylated ASGP-1 on paraffin-embedded sections of parotid, submaxillary
      and sublingual tissues was performed to examine the localization of the mucin in
      the major rat salivary glands. Histological and immunocytochemical staining of
      cell markers showed that the salivary glands consisted of varying numbers of
      serous and mucous acini which are drained by ducts. Parotid glands were composed
      almost entirely of serous acini, sublingual glands were mainly mucous in
      composition and a mixture of serous and mucous acini were present in submaxillary
      glands. Since immunoreactive (ir)-SMC was specifically localized to the serous
      cells, staining was most abundant in parotid glands, intermediate levels in
      submaxillary glands and least in sublingual glands. Ir-SMC in sublingual glands
      was localized to caps of cells around mucous acini, known as serous demilunes,
      which are also present in submaxillary glands. Immunocytochemical staining of SMC
      in human parotid glands was localized to epithelial cells of serous acini and
      ducts. However, the staining pattern of epithelial cells was heterogeneous, with
      ir-SMC present in some acinar and ductal epithelial cells but not in others. This
      report provides a map of normal ir-SMC/Muc4 distribution in parotid, submaxillary
      and sublingual glands which can be used for the study of SMC/Muc4 expression in
      salivary gland tumors.

PMID- 11292168
TI  - Role of male accessory glands in spermatodesm reorganization in Orthoptera
      Tettigonioidea.
AB  - A preliminary examination of the spermatodesms of Orthoptera Tettigonioidea
      revealed a structure that is similar in individuals of the same sex but very
      different in specimens of opposite sex. This reorganization would seem to take
      place inside the spermatophore during transit from the male to female genital
      tracts. The results of incubating spermatodesms with the secretions of glandular
      extract (GE) obtained from male accessory glands, known to be involved in forming
      the spermatophore wall, revealed changes in the spermatodesm 'cap' that are
      comparable to those occurring in vivo. Moreover, incubation of spermatodesms with
      the extracts obtained separately from tubules of the 1st and 2nd orders (GE1,
      GE2) established that GE2 alone modifies the spermatodesms, thus excluding the
      possible implication of 1st order tubules in the rearrangement process. In
      conclusion, data from incubations of spermatodesms with the single fractions
      obtained by submitting GE2 to gel-filtration FPLC show that only the peak 4
      maintains intact the biological activity of GE2, SDS-PAGE analysis of the
      fraction corresponding to peak 4 revealed a greater protein content of 29 kD,
      which also appears to a lesser degree in fraction 3. This material is responsible
      for a partial dismantling of the 'cap' in the incubated spermatodesms.

PMID- 11292167
TI  - Expression of cyclin-dependent kinase inhibitors in taste buds of mouse and
      hamster.
AB  - Taste buds are specialized epithelial cell clusters in the oral squamous cell
      epithelium. Although taste buds have been reported to renew rapidly, the
      mechanism of cell cycle control in these specialized structures remains
      unresolved. To clarify the cell cycle status and role of cyclin-dependent kinase
      inhibitors (CDKI) for cell cycle control in the taste buds, we analyzed cell
      proliferation activity using bromodeoxyuridine (BrdU) and Ki-67 immunostainings
      and the expression of the Cip/Kip family of CDKI (p21Cip1, p27Kip1, and p57Kip2)
      in the circumvallate papillae of mouse and hamster. BrdU-positive cells were
      detected in the basal layer of the oral epithelium. In the taste buds, Ki-67
      positive cells were seen in the basal area, with only a very few positive cells
      in the taste buds. Both p21Cip1 and p27Kip1 positive cells were seen in the
      suprabasal layer of the non-gustatory oral epithelium. In the taste buds,
      stronger p27Kip1 staining was detected than in the non-gustatory epithelium.
      Western blotting analysis revealed that p27Kip1 was abundant in the mucosal
      tissues from circumvallate papillae. Thus, our study suggests that the taste bud
      cells except for basal cells are post-mitotic cells and that the cell cycle
      arrest associated with taste bud cell differentiation could be regulated
      predominantly by p27Kip1.

PMID- 11292169
TI  - Coexpression of cytokeratin and vimentin in mice trophoblastic giant cells.
AB  - Trophoblastic giant cells reach their maximum size and exhibit a conspicuous
      synthetic and invasive activity during mouse placentation. The cytoskeleton,
      given the complex functions of the cells, shows a well-developed network of
      intermediate filament proteins. Immunohistochemistry combined with confocal and
      conventional immunofluorescence studies of intermediate filaments proteins
      cytokeratin and vimentin were performed in mice trophoblastic giant cells on days
      9-11 of pregnancy. Specimens were fixed in phosphate-buffered formaldehyde and
      tissues were processed for routine paraffin embedding. Trophoblastic giant cells
      from antimesometrial, lateral or mesometrial uterine regions, through days 9-11
      of pregnancy, expressed the same staining with both immunoperoxidase and
      immunofluorescent techniques. Cytokeratin filamentous structures were intensely
      immunoreactive and were detected throughout the cells cytoplasm; a few cells
      exhibited strongest fluorescence in the peripheral cytoplasm. Vimentin-positive
      staining was often distributed throughout the cells cytoplasm, most frequently
      and more intensely in the peripheral region; in some cells, it was present only
      in the peripheral regions. It is probable that expression of vimentin in
      midpregnancy trophoblastic giant cells may be associated with the rapid and
      conspicuous increase in size and synthetic activity of the cells and also with
      phagocytosis of degraded materials and invasion of decidual tissue.

PMID- 11292170
TI  - Fine structure of the skin cells of a stenohaline freshwater fish Cyprinus carpio
      exposed to diluted seawater.
AB  - Seawater diluted to half (1.750% salinity) is lethal for adult carps after 3 h
      and 15 min. At lower salinities (0.350%-0.875%), the fish survived for longer
      periods, but only 0.175% salinity was innocuous. In carps, adapted to 0.175%
      salinity, the secretory activity of pavement cells was very high and their
      external ridges flattened or even disappeared. Mucus secretion was conspicuous,
      characterized by holocriny of old cells and apparition of young ones in large
      numbers. The intracellular mucus droplets often coalesced. Pavement cells and
      mucus cells were disconnected from their neighboring tissue fabric and were
      sloughing off. Mitotic figures of filament cells were frequent, suggesting high
      turnover. Club cells appeared near the epidermal surface. The number of
      pinocytotic vesicles of the basal cell layer markedly decreased, indicating a
      possible decrease in dermis-epidermis molecular transfers. Leucocytes, mainly
      lymphocytes penetrated into the epidermis, where also rodlet cells appeared. The
      low salinity tolerance of the carp might be related among other possible factors
      to the absence of chloride cells in the skin.

PMID- 11292171
TI  - Ultrastructural study of protein kinase C-betaII localization during the cell
      cycle of human glioma cells.
AB  - Transmission electron microscopy and immunogold labeling were used to determine
      how PKC-betaII is localized at stages in the cell cycle of the human glioma cell
      line U-373MG. Results show that immunogold particles in both dimethylsulfoxide
      (DMSO) and calphostin C (0.5 microM)-treated cells were mainly located in the
      cytoplasm. The concentration of gold particles in the nucleus was relatively
      small and constant throughout the cell cycle of both DMSO and calphostin C
      treated cells. Micrographs revealed changes in PKC-betaII during the cell cycle.
      The concentration of gold particles in the DMSO-treated cells was constant until
      8 h. Subsequently, cytoplasmic PKC-betaII oscillated with an increased at 10 h, a
      rapid decrease at 12 h, and a rise at 14 h. The concentration of the gold
      particles then gradually decreased. In contrast, immunogold labeling in
      calphostin C-treated cells increased gradually up to 10 h. Subsequently, the
      pattern of PKC-betaII labeling in calphostin C-treated cells recapitulated those
      of control cells as seen by the rapid decline of PKC-betaII labeling at 12 h and
      its re-accumulation at 14 h. Additionally, there was a rapid increase at 20 h.
      Western blots of PKC-betaII showed constant PKC-betaII immunoreactivity
      throughout the cell cycle. In comparison to Western blots, in-situ immunogold
      labeling revealed changes in PKC-II immunoreactivity at 10 h and 14 h. This
      technique may represent intracellular immunoreactivity of PKC-betaII. The results
      from the immunogold labeling technique suggest that binding of calphostin C to
      the regulatory domain of PKC-betaII provokes a conformation change in PKC-betaII,
      preventing its activation and degradation.

PMID- 11292172
TI  - Light and transmission electron microscopy of the dorsal lingual epithelium of
      Pelusios castaneus (Pleurodira, Chelidae) with special respect to its feeding
      mechanics.
AB  - The ultrastructure of the dorsal lingual epithelium of the semi-aquatic West
      African mud turtle, Pelusios castaneus, is described. Our goal is to give
      additional information to previous studies of this species such as feeding
      pattern analysis and gross morphology. Tissue specimens were fixed in modified
      Karnovsky solution followed by osmium tetroxide, embedded in epoxy resin and
      observed using light and transmission electron microscopy. The dorsal tongue
      surface is covered with moderate papillae, which are coated by a stratified
      epithelium overlying a connective tissue core. Two epithelial regions can be
      differentiated, although differences are not very obvious: the apical area, where
      granular cells are more abundant than mucus cells, and the lateral area, where
      cell distribution is opposite. Within the epithelium, different layers are
      discernable on the basis of the cells' organelles, corresponding with a process
      of cell maturation and formation of different granules. These results together
      with data of previous studies of this species show that the ultrastructure of the
      lingual epithelium is similar to other turtles adapted to semi-aquatic
      environments; functional and morphological data indicate a generalist, being well
      but not highly adapted to feeding in an aquatic environment.

PMID- 11292173
TI  - Zinc iodide-osmium tetroxide (ZIO) reactive sites in the extrafloral nectary of
      Citharexylum mirianthum Cham. (Verbenaceae).
AB  - This paper reports on a study of the zinc iodide-osmium tetroxide method (ZIO)
      applicability to formaldehyde-glutaraldehyde prefixed extrafloral nectary tissues
      of Citharexylum mirianthum Cham. (Verbenaceae). The ZIO solution impregnates the
      dictyosome stacks and adjacent vesicles, smooth endoplasmic reticulum, nuclear
      envelope, multivesicular bodies, and peroxisomes. The use of this method greatly
      facilitates the observation and recognition of organelles in each nectary region.
      It also allows the correlation between structure and function in nectariferous
      cells.

PMID- 11292174
TI  - Ultrastructural studies of late-stage spermatids and mature spermatozoa of the
      puffer fish, Takifugu niphobles (Tetraodontiformes) and the effects of osmolality
      on spermatozoan structure.
AB  - Ultrastructures of late-stage spermatids and spermatozoa, and of spermatozoa
      after exposure to various osmolalities, were studied in the puffer, Takifugu
      niphobles. The mature spermatozoa consisted of a head, a midpiece of many
      mitochondria and a flagellum with sharp sidefins, had many ring-structures just
      inside of the plasma membrane of cytoplasmic sleeve and triangular-structures
      projecting into cytoplasmic canal at the base of flagellum. In late spermatids,
      the rings and projections were present, but the side-fins had round ends and the
      cytoplasm of flagellum was amorphous. When spermatozoa were exposed to seawater,
      the plasma membrane became swollen in the head-midpiece region but shrank in the
      tail region. In 1/2 seawater, swelling in the tail occurred in some spermatozoa.
      In 1/3 seawater approximately isotonic to the seminal plasma, there was little
      change. In 1/10 seawater, the plasma membrane swelled slightly in the head
      region, but swelled much more in the tail region. In buffer solution, the
      membrane swelled in all regions, surrounding the nucleus and many sections of
      axoneme. Thus, function of the plasma membrane in the head-region may be
      different from that in the tail-region. Spermatozoa of marine fish may fertilize
      the eggs when the osmolality surrounding the sperm, which changes due to the
      mixing of seminal plasma and seawater, reaches the correct level for the
      spermatozoa to obtain correct structure.

PMID- 11292175
TI  - Cytology of the interstitial tissue in scrotal and abdominal testes of post
      puberal boars.
AB  - The interstitial tissue of the testes from healthy boars, and unilateral and
      bilateral abdominal cryptorchid boars was examined by light and transmission
      electron microscopy. The left and right testes of healthy boars, and the left
      (scrotal) testis of unilateral cryptorchid boars had abundant mature Leydig
      cells, few fibroblasts and mast cells, scarce and small blood vessels, and little
      lymphatic areas. The right (abdominal) testis of unilateral cryptorchid boars
      contained abundant Leydig cells, fibroblasts and erythrocytes, scarce mast cells,
      and frequent blood vessels; Leydig cells exhibited either a mature but
      degenerative appearance or an immature appearance, and fibroblasts displayed
      immaturity signs. The interstitial tissue of the left (abdominal) testes of
      bilateral cryptorchid boars had small blood vessels surrounded by erythrocytes,
      lymphocytes, and few plasma cells, and abundant mature and immature Leydig cells,
      immature fibroblasts, and mast cells. Mature Leydig cells showed mid or advanced
      degeneration, and immature Leydig cells displayed either non-degenerative or
      degenerative patterns. The right (abdominal) testes of bilateral cryptorchid
      boars contained scarce immature Leydig cells in advanced degeneration, large
      fibrous and adipose areas, and blood vessels. These results indicated that
      unilateral abdominal cryptorchidism affect neither the structural nor the
      cytologic features of the interstitial tissue in scrotal testes. Unilateral and
      bilateral cryptorchidism induced abnormal differentiation of Leydig cells and
      fibroblasts leading to decreased steroid production and increased collagenization
      in abdominal testes.

PMID- 11292176
TI  - Use of conditionally immortalized mouse cardiac fibroblasts to examine the effect
      of mechanical stretch on alpha-smooth muscle actin.
AB  - Mechanical stretch regulates alpha-smooth muscle actin (SMA) expression in
      myofibroblasts but limited replication and cellular heterogeneity have hampered
      definitive studies in vitro. We examined the role of applied force in regulating
      SMA expression in conditionally immortalized cardiac fibroblast lines derived
      from H-2Kb-tsA58 transgenic mice. When plated in differentiating conditions (37
      degrees C without interferon-gamma), transgenic myofibroblasts exhibited vimentin
      staining, no desmin staining and abundant SMA in well-developed stress fibers
      that were indistinguishable from controls. Magnetically-generated tensile forces
      (approximately 500 pN/cell) applied through collagen-coated magnetite beads
      selectively reduced SMA but not beta-actin mRNA and protein content in both cell
      types. The early loss of SMA was due in part to selective leakage into the cell
      culture medium. Depolymerization of actin filaments with cytochalasin D blocked
      the force-induced reduction of SMA. Cardiac fibroblast lines established from H
      2Kb-tsA58 transgenic mice provide a phenotypically stable source of cells for
      studying the role of physical forces in regulating SMA.

PMID- 11292177
TI  - The effects of collagen synthesis inhibitory drugs on somitogenesis and myogenin
      expression in cultured chick and mouse embryos.
AB  - The role of fibrillar collagen on myogenic differentiation has previously been
      studied in tissue culture cell lines but has not been studied in situ. We treated
      cultured chick and mouse embryos with collagen synthesis inhibitors to determine
      the role of fibrillar collagen on somitogenesis and on myogenic differentiation
      in vivo. Stage 12 chick embryos and 8.7 dpc mouse embryos were cultured in
      control medium or a range of concentrations of the collagen synthesis inhibitors
      ethyl-3,4-dihydroxybenzoate (EDHB) or cis-hydroxy-proline (CHP). Chick embryos
      were cultured for 24 h and mouse embryos were cultured for 30 h. Both collagen
      synthesis inhibitors produced a range of somite abnormalities including formation
      of fewer and irregular somites in both chick and mouse at high drug
      concentrations, as well as formation of double somites in EDHB-treated chick
      embryos. Examination of EDHB-treated mouse embryos by scanning electron
      microscopy demonstrated a dosage-dependent loss of fibrillar collagen and
      associated extracellular matrix. Expression of myogenin in EDHB-treated mouse
      embryos, examined by whole-mount in situ hybridization, was suppressed at higher
      dosage levels. This study suggests that inhibition of fibrillar collagen
      production and/or loss of fibrillar collagen in the developing avian and
      mammalian embryo results in abnormal somite formation and perturbed myogenic
      differentiation.

PMID- 11292178
TI  - Further study of aldosterone secretion-inhibitory factor and brain natriuretic
      peptide on cortisol production of guinea pig zona fasciculata cells.
AB  - The suppressive effect of aldosterone secretion-inhibitory factor (ASIF) and
      brain natriuretic peptide (BNP-32) on the basal and ACTH-stimulated cortisol
      production in a primary culture enriched with guinea pig Zona Fasciculata (ZF)
      cells was further studied. The binding of 125I-labeled ACTH(1-24) and ASIF to ZF
      cells was found to be displaced by ACTH(1-24), [Phe2, Nle4 and Ala24]-ACTH(1-24),
      ASIF, and BNP in a concentration-dependent manner. The binding of 125I-labeled
      [Phe2, Nle4 and Ala24]-ACTH(1-24) to two transformed clones of mammalian cells
      expressing the guinea pig ACTH receptor was also competitively inhibited by ASIF
      and BNP. ASIF and BNP significantly suppressed ACTH-stimulated cAMP production in
      ZF cells. The 10- and 30-min cellular changes in cAMP induced by ASIF and BNP did
      not correlate in the rank order with the ultimate magnitude of cortisol
      suppression observed in ZF cells after a 24-hour treatment with these peptides.
      Nevertheless, the results did conform to the signaling mechanism of their action.
      Overall, the findings clearly demonstrated that ASIF and BNP suppressed the
      adrenocortical function and inhibited ACTH for their antagonistic action against
      ACTH primarily at the ACTH receptor site. These results support the notion that a
      physiological role of adrenal medulla in regulating the adrenocortical function
      may be mediated by the neuropeptides through a paracrine pathway.

PMID- 11292179
TI  - Alterations in Ca2+ signaling, and c-fos and nur77 expression are associated with
      sodium butyrate-induced differentiation of C6 glioma cell.
AB  - Sodium butyrate is well known in stimulating growth and differentiation of cancer
      cells. In the present study, butyrate treatment caused decreases in thymidine
      incorporation in the early passages (45-60) of C6 glioma cells. In addition,
      butyrate also caused decreases in inositol incorporation and transient ATP
      stimulated Ca2+ mobilization suggesting that butyrate altered general mechanisms
      of Ca2+ signaling in these cells. To gain direct insight into the crosstalk
      between sodium butyrate and Ca2+ signaling in transcriptional regulation, we
      investigated the induction of the Ca2+-sensitive immediate early genes (IEGs), c
      fos, nur77 and c-myc. Sodium butyrate per se enhanced the expression of c-fos
      mRNA, and the enhanced levels were maintained for 24 h, but over the same time
      period, the initially increased levels of nur77 expression tailed off, while c
      myc expression was slightly reduced. Increasing intracellular Ca2+ concentration
      ([Ca2+]i) by thapsgargin and A23187 induced the expression of both c-fos and
      nur77 mRNA expression, and synergistic effects were observed when cells were
      incubated with sodium butyrate plus thapsgargin and A23187. However, removal of
      both extracellular Ca2+ by EGTA, or intracellular free Ca2+ with BAPTA did not
      affect the sodium butyrate-induced c-fos and nur77 mRNA. These results suggest
      that although sodium butyrate altered Ca2+ signaling which is an important
      regulatory mechanism for c-fos and nur77 expression, nevertheless the sodium
      butyrate-induced c-fos and nur77 expression may be not in fact mediated through
      Ca2+ signaling.

PMID- 11292180
TI  - Effect of age and sex on plasma total homocysteine in Taiwanese subjects.
AB  - Plasma total homocysteine (tHcy) is now established as a clinical risk factor for
      coronary artery disease, as well as for other arterial and venous occlusive
      diseases. Therefore, we measured the plasma tHcy concentrations in 385 healthy
      Chinese subjects in Taiwan and in 40 patients with occluded coronary artery
      disease or maintenance hemodialysis. The plasma tHcy levels in Taiwanese male and
      female volunteers were found to increase gradually with age (age group: 20-29, 30
      39, 40-49, 50-59, and >60; mean +/- SD 8.22 +/- 2.00, 8.51 +/- 2.67, 8.87 +/-
      2.22, 11.41 +/- 2.50 and 13.28 +/- 2.31 microM for male volunteers and 6.49 +/-
      1.75, 7.15 +/- 1.20, 7.40 +/- 1.30, 9.57 +/- 3.01 and 10.95 +/- 2.11 microM for
      female volunteers). At the same age, male volunteers were shown to have higher
      tHcy levels than female volunteers. In addition, the mean concentrations of
      plasma tHcy in occluded coronary artery disease (13.62 +/- 5.43 microM) or in
      maintenance hemodialysis (21.28 +/- 4.32 microM) were statistically higher than
      in age-matched normal subjects (11.02 +/- 2.85 microM). This study emphasizes the
      significance of age and sex-associated difference in the plasma tHcy levels, and
      underlines the importance of the range for plasma homocysteine in normal
      Taiwanese subjects.

PMID- 11292181
TI  - Histamine-Induced increases in intracellular free Ca2+ levels in hepatoma cells.
AB  - The effect of histamine on intracellular free Ca2+ levels ([Ca2+]i) in HA22/VGH
      human hepatoma cells were evaluated using fura-2 as a fluorescent Ca2+ dye.
      Histamine (0.2-5 microM) increased [Ca2+]i in a concentration-dependent manner
      with an EC50 value of about 1 microM. The [Ca2+]i response comprised an initial
      rise, a slow decay, and a sustained phase. Extracellular Ca2+ removal inhibited
      50% of the [Ca2+]i signal. In Ca2+-free medium, after cells were treated with 1
      microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 5 microM
      histamine failed to increase [Ca2+]i. After pretreatment with 5 microM histamine
      in Ca2+-free medium for 4 min, addition of 3 mM Ca2+ induced a [Ca2+]i increase
      of a magnitude 7-fold greater than control. Histamine (5 microM)-induced
      intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2
      microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole
      2,5-dione (U73122), and by 5 microM pyrilamine but was not altered by 50 microM
      cimetidine. Together, this study shows that histamine induced [Ca2+]i increases
      in human hepatoma cells by stimulating H1, but not H2, histamine receptors. The
      [Ca2+]i signal was caused by Ca2+ release from thapsigargin-sensitive endoplasmic
      reticulum in an inositol 1,4,5-trisphosphate-dependent manner, accompanied by
      Ca2+ entry.

PMID- 11292182
TI  - Capsaicin pre- and post-treatment on rat monocrotaline pneumotoxicity.
AB  - Monocrotaline (MCT) produces respiratory dysfunction, pulmonary hypertension
      (PH), and right ventricular hypertrophy (RVH) in rats. Tachykinins, such as
      substance P (SP) and neurokinin A (NKA), may mediate these effects. The purpose
      of this study was to investigate the length of tachykinin depletion (via
      capsaicin treatment) is needed to prevent (or attenuate) PH and/or RVH. Six
      groups of rats were injected subcutaneously with saline (3 ml/kg); capsaicin
      followed by saline or MCT (60 mg/kg); or MCT followed 7, 11, or 14 days later by
      capsaicin. Capsaicin (cumulative dose, 500 mg/kg) was given over a period of 4-5
      days. Respiratory function, pulmonary vascular parameters, lung tachykinin
      levels, and tracheal neutral endopeptidase (NEP) activity were measured 21 days
      after MCT or saline injection. Capsaicin significantly decreased lung levels of
      SP but not NKA. Both capsaicin pretreatment and posttreatment blocked the
      following MCT-induced alterations: increases in lung SP and airway constriction;
      decreases in tracheal NEP activity and dynamic respiratory compliance.
      Administration of capsaicin before or 7 days after MCT blocked MCT-induced PH and
      RVH. The above data suggest that the early tachykinin-mediated airway dysfunction
      requires only transient elevated tachykinins, while progression of late
      tachykinin-mediated effects (PH and RVH) requires elevated tachykinins for more
      than one week.

PMID- 11292184
TI  - Different roles of two subgroups of lung vagal C-fiber afferents in the
      tachypneic response to pulmonary air embolism in dogs.
AB  - It is known that lung vagal C-fiber afferents play an important role in eliciting
      the tachypneic response to pulmonary air embolism (PAE), and can be subgrouped as
      those with low resistance (LRC) and those with high resistance (HRC) to perivagal
      capsaicin. In this study, we investigated the relative contributions of vagal LRC
      and HRC C-fiber afferents to the PAE-induced tachypneic response. Phrenic
      activity was recorded from 10 anesthetized, paralyzed, and artificially
      ventilated dogs. PAE was induced by infusion of air into the vein (2 ml/min, 1
      ml/kg). During control conditions, induction of PAE produced a shortening in
      expiratory duration with no significant change in inspiratory duration, resulting
      in tachypnea. The PAE-induced tachypneic response was totally abolished by
      perivagal capsaicin treatment with a method (capsaicin concentration, 6 mg/ml;
      treatment duration, 25-30 min) that blocks the conduction of LRC C-fiber
      afferents, but not that of HRC C-fiber afferents. This tachypneic response was
      not affected by cooling of both vagi to a temperature (4.5 degrees C) that blocks
      the conduction of HRC C-fiber afferents, but not that of LRC C-fiber afferents. A
      bilateral cervical vagotomy virtually eliminated this tachypneic response. These
      results suggest that LRC C-fiber afferents are responsible for eliciting the
      reflex tachypneic response to PAE, whereas HRC C-fiber afferents play no vital
      role.

PMID- 11292183
TI  - Study the mechanisms of U-50,488 to prevent the development of morphine tolerance
      in guinea pigs.
AB  - Previously we have shown that low dose of [trans-3,4-dichloro-N-methyl-N-[2-(1
      pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride] (U-50,488) could prevent
      the development of morphine tolerance in guinea pigs. In the present study we
      tried to investigate the role of glutamate and nitric oxide in this process. Male
      Hartley guinea pigs (200-300 g) were chronically treated s.c. with either saline
      or morphine (15 mg/kg) or morphine + U-50,488 (0.003 mg/kg) twice a day for 7
      days. Antinociceptive activity was assessed by hot-plate test on the first,
      fourth and seventh day. Spinal cord slices (450 microm) were prepared 30 min
      after drug treatment on eighth day and [3H] glutamate and nitric oxide (NO)
      released were determined. We found that coadministration of U-50,488 (0.003
      mg/kg) suppressed the development of morphine tolerance to antinociceptive effect
      as we reported before. The percentage of in vitro spinal release of [3H]
      glutamate by 100 microM morphine was significantly higher in the chronic morphine
      group than the control group. On the other hand, coadministration of U-50,488
      with morphine for 7 days blocked this effect significantly. The basal NO level
      released from the spinal cord slices was significantly higher in chronic morphine
      group but not in chronic (morphine + U-50,488) group. In vitro morphine (100
      microM) increased the NO level in control group and chronic (morphine + U-50,488)
      group and also further increased NO in chronic morphine group. From the NMDA
      displaced [3H] glutamate binding in guinea pig spinal cord, we found that the
      Bmax decreased in chronic morphine group but not in the chronic (morphine + U
      50,488) group. In conclusion, chronic morphine treatment may activate the NMDA
      receptors by increasing the release of glutamate which causes the increase of
      synthesis and release of NO and following uncertain mechanisms to induce the
      development of morphine tolerance. And the mechanisms of U-50,488 to prevent the
      development of morphine tolerance may involve the inhibition of glutamate
      released by chronic morphine and also the decrease of NO induced by chronic
      morphine.

PMID- 11292185
TI  - Atypical variant of acquired von Willebrand syndrome in Wilms tumor: is
      hyaluronic acid secreted by nephroblastoma cells the cause?
AB  - Acquired von Willebrand syndrome (AvWS) has been reported in eight children with
      Wilms tumor (nephroblastoma in four boys and four girls) at a mean age of 3.3
      years (range, 0.33-9 years). Only three of eight patients with AvWS in Wilms
      tumor presented with mild mucocutaneous bleeding symptoms. The AvWS in seven
      children with Wilms tumor featured either undetectable or very low von Willebrand
      factor antigen (vWF.Ag) levels (mean, 3%) and decreased values for vWF ristocetin
      cofactor (RCF) activity (mean, 20%) and factor VIII coagulant (VIIIc) activity
      (mean, 16%). The response to 1-desamino-8-arginine vasopressin (DDAVP) was good
      in two and poor in one patient. Multimeric analysis of the vWF showed a normal
      pattern of type I von Willebrand disease (vWD) in three patients and an absence
      of multimers consistent with type III vWD in two patients. The higher functional
      levels, as compared with antigen levels, with increased ratios for factor
      VIIIc/vWFAg (mean, 5.3) and vWF.RCF/vWF.Ag (mean, 6.6) in seven patients with
      Wilms tumor are unexplained physiologically and are not consistent with type I
      vWF deficiency. The absence of vWD in the patient's family, and the return of
      factor VIII-vWF parameters to normal after chemotherapy or surgical removal of
      the Wilms tumor, support the diagnosis of AvWS causally related to the Wilms
      tumor. The causative agent is thought to be hyaluronic acid secreted by
      nephroblastoma cells of the Wilms tumor. Prospective studies to determine the
      nature of AvWS in children with Wilms tumor are warranted.

PMID- 11292186
TI  - Acquired von Willebrand syndrome in systemic lupus erythematodes.
AB  - Acquired von Willebrand syndrome (AvWS) in systemic lupus erythematodes (SLE) is
      caused by autoantibodies directed against the circulating von Willebrand factor
      (vWF)/factor VIII (FVIII) complex. The autoantibody-vWF/FVIII antigen complex is
      cleared rapidly from the circulation, leading to a moderate to severe
      quantitative and qualitative deficiency of both vWF and FVIIIc. Consequently,
      AvWS in SLE is featured by a prolonged bleeding time and normal platelet count, a
      prolonged activated partial thromboplastin time (APTT) and normal prothrombin
      time (PT), decreased or absent ristocetin-induced platelet aggregation (RIPA),
      and type II vWF deficiency on multimeric analysis of the vWF protein. Acquired
      von Willebrand syndrome type II in SLE responds poorly to 1-desamino-8-D-arginine
      vasopressin (DDAVP) and FVIII concentrate, but responds transiently well to high
      dose gammaglobulin given intravenously. All reported cases of AvWS in SLE were
      cured by appropriate treatment of the underlying autoimmune disease with
      prednisone or immunosuppression.

PMID- 11292187
TI  - Acquired von Willebrand syndrome type 1 in hypothyroidism: reversal after
      treatment with thyroxine.
AB  - In 16 cases, acquired von Willebrand syndrome (AvWS) and hypothyroidism have been
      described that occur with each other: 15 women and one man, at a mean age of 32
      years, range, 13 to 82 years of age. Activated partial thromboplastin time (APTT)
      was normal in six patients, and five patients had factor VIII concentration
      (factor VIIIc) levels in excess of 60%. The bleeding time was prolonged in nine
      of 13 evaluable patients. Activated partial thromboplastin time was prolonged in
      seven patients, and five of these had factor VIIIc levels between 18 and 45%,
      with two patients having levels in excess of 60%. A deficiency of other
      coagulation factors, including factor VII, V, IX, and X, caused by a generalized
      diminution in protein synthesis in hypothyroidism, may have contributed to the
      prolongation of the APTT. The AvWS was very likely type 1 in all cases because of
      a normal von Willebrand factor antigen/ristocetin cofactor (vWF Ag/RCF) ratio.
      Acquired von Willebrand syndrome was documented via cross immunoelectrophoresis
      in three patients and via multimeric analysis of vWF in six patients. A definite
      diagnosis of AvWS type I has to be confirmed by a normal response to 1-desamino-8
      D-arginine vasopressin (DDAVP). Treatment of hypothyroidism with thyroxine was
      associated with the disappearance of the AvWS and the bleeding diathesis.
      Decreased factor VIIIc, vWF Ag and vWF RCF levels (50%, 33%, and 36%
      respectively) before thyroxine treatment increased to normal values (97%, 93%,
      and 107% respectively) after treatment. The absence of bleeding, or mild
      bleeding, symptoms, in relation to those more commonly recognized with
      hypothyroidism, has led to the complication of acquired vWF deficiency being
      underdiagnosed. Acquired von Willebrand syndrome type I should be considered
      whenever hypothyroidism is diagnosed and thyroid biopsy or surgery is
      contemplated. The complete relief of AvWS via treatment of hypothyroidism with
      thyroxine is the final proof of this association and causal relationship.

PMID- 11292188
TI  - Platelet and leukocyte deactivation after intracoronary stent placement in
      patients receiving combined antiplatelet therapy.
AB  - Activated platelets and leukocytes have been demonstrated to play a role in the
      development of stent thrombosis, and coronary angioplasty has been shown to
      result in activation of platelets, leukocytes, and endothelial cells. We aimed to
      evaluate the effects of intracoronary stent placement and aspirin plus
      ticlopidine treatment on platelets, leukocytes, and endothelial cells via
      observing the serial changes in the circulating soluble forms of adhesion
      molecules in 54 patients with coronary artery disease, who had elective coronary
      angioplasty and stent implantation for a single lesion of the left anterior
      descending artery. After stent placement, intravenous heparin infusion was
      administered only for 24 hours, and aspirin plus ticlopidine treatment was
      applied for 1 month. Venous blood samples were drawn before stent placement, and
      repeated 24 and 48 hours after the procedure. Patients were excluded if they had
      had recent cardiovascular events or any illness that might influence platelet,
      leukocyte, and endothelial cell function. The plasma level of sL-selectin was
      significantly decreased 48 hours after coronary stenting (636+/-110 ng/mL vs
      567+/-93 ng/mL; P = 0.001, respectively). Likewise, the plasma level of sP
      selectin was also decreased significantly 48 hours after the procedure (260+/-61
      ng/mL vs 233+/-83 ng/mL, P = 0.01). The sE-selectin level was found to be
      significantly increased 24 hours (31+/-9 ng/mL vs 39+/-12 ng/mL, P = 0.0001) and
      48hours(31+/-9 ng/mL vs 42+/-15 ng/mL, P = 0.001) after coronary stenting. The
      results of our study suggest that significant platelet and leukocyte deactivation
      take place in patients treated with combined antiplatelet therapy after stenting;
      endothelial cell activation also occurs during this treatment.

PMID- 11292189
TI  - Homozygous patients with the 20210 G to A prothrombin polymorphism remain often
      asymptomatic in spite of the presence of associated risk factors.
AB  - Patients who are homozygous for the G to A nontranslated prothrombin polymorphism
      only occasionally have venous thrombosis. An evaluation of all published papers
      on the subjects has disclosed that nine patients of the 35 so far reported
      remained asymptomatic in spite of the presence of associated congenital or
      acquired thrombotic risk factors. We saw an additional patient recently, bringing
      the total to 10 of 36 patients. Some of these patients remained asymptomatic in
      spite of multiple or repetitive risk factors (e.g., five pregnancies in the case
      of one patient). Twelve patients who were homozygous and who had this
      polymorphism developed symptoms only in the presence of the same risk factors.
      This may suggest that this abnormality played a small role, if any, in both
      groups of patients. The finding that several patients with this abnormality
      remained asymptomatic in spite of associated risk factors casts serious doubts
      about the prothrombotic significance of this polymorphism. Until this problem is
      clarified, the clinician must abstain from attributing a prothrombotic effect to
      this polymorphism.

PMID- 11292190
TI  - Cytokines, endothelium, and adhesive molecules in pathologic thrombopoiesis.
AB  - Clonal thrombocytosis (CT) associated with myeloproliferative disorders (MPD) is
      believed to be secondary to autonomous unregulated platelet production. Secondary
      or reactive thrombocytosis (RT) can be observed in a number of clinical
      circumstances and may be related to persistent production of some thrombopoietic
      factors acting on megakaryocytes (MK). The goal of this study is to assess the
      serum concentrations of these cytokines in control subjects and patients with MPD
      associated with thrombocythemia, RT, and autoimmune thrombocytopenic purpura
      (ATP). Eleven patients with MPD, five with chronic myeloid leukemia (CML), three
      with polycythemia vera (PCV), two with essential thrombocythemia (ET), one with
      myelofibrosis, 15 with RT, eight with ATP, and 12 healthy volunteers were
      enrolled in the study. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor
      alpha (TNF), fibronectin, intracellular adhesion molecule-1 (ICAM-1), and
      thrombomodulin (TM) were measured in these groups. Interleukin- 1beta, IL-6, and
      TNF levels were high in patients with RT and ATP, suggesting that these cytokines
      act on early uncommitted progenitors, promoting commitment along the MK lineage
      and leading to thrombocytosis or compensation for thrombocytopenia. TM was
      significantly increased in patients with MPD compared to all other groups,
      probably indicating the presence of subclinical endothelial damage. Fibronectin
      levels were high in MPD and RT patients. This finding can be secondary to high
      platelet turnover in these patients. We found that ICAM-1 levels were high in
      patients with clonal thrombocytosis. ICAM-1 can be one of the factors initiating
      the events ultimately leading to clonal thrombocytosis. Thrombocythemia
      associated with MPD is an autonomous phenomenon not regulated by cytokines.

PMID- 11292191
TI  - Anticoagulant and antiprotease profiles of a novel natural heparinomimetic
      mannopentaose phosphate sulfate (PI-88).
AB  - Heparinomimetic mannopentaose phosphate sulfate (PI-88) (Progen Industries Ltd.
      Brisbane, Australia), currently developed as an anticoagulant and
      antiproliferative agent, mainly is composed of a pentomannan. However,
      tetrasaccharide and disaccharide components are also present. The molecular
      profile and the anticoagulant potency of PI-88 are investigated in this study.
      Gel permeation chromatography and polyacrylamide gel electrophoresis analyses
      were carried out to determine the molecular profile and separation of components
      of PI-88, respectively. Potentiation of antithrombin III (ATIII) and heparin
      cofactor-II (HC-II) activity were measured using chromogenic substrate assay. In
      order to determine anticoagulant and antiprotease effects of PI-88, various
      global anticoagulant tests, such as the prothrombin time (PT), activated partial
      thromboplastin time (APTT), thrombin time (TT), Hep-test (Haemachem Inc., St.
      Louis), ecarin clotting time (ECT), activated clotting time (ACT), and
      thromboelastography (TEG) were used. Anti-Xa and anti-IIa activities also were
      measured. The effect of PI-88 on the release of tissue factor pathway inhibitor
      (TFPI) was performed in nonhuman primates who received PI-88 and in endothelial
      cell culture systems. The relative susceptibility of PI-88 to heparinase I,
      protamine sulfate (PS), and platelet factor 4 (PF4) also was evaluated. The high
      performance liquid chromatography profiles of PI-88 showed that its average
      molecular weight is approximately 2300 Da. Separation and gradient
      electrophoretic patterns of PI-88 showed that it is composed of five different
      fractions. This agent activates HC-II through inhibiting the thrombin generation
      but not inhibiting ATIII. Although PI-88 produced a concentration-dependent
      prolongation of all of the clotting tests, ECT gave the best correlation in the
      dose-response curve (ECT, r2 = 0.94; TT, r2 = 0.84; APTT, r2 = 0.69).
      Heparinomimetic mannopentaose phosphate sulfate (PI-88) exhibited marked
      inhibition of FIIa, but not of FXa. Heparinase I failed to produce significant
      neutralization of PI-88 in all the assays used, whereas PS and PF4 partially
      neutralized the effects of this compound. Heparinomimetic mannopentaose phosphate
      sulfate (PI-88) produced fivefold increase in the TFPI levels at 15 minutes after
      intravenous (IV) injection to primates. The incubation of PI-88 in endothelial
      cell culture system also showed a strong effect on TFPI release. These results
      suggest that PI-88 exhibited strong antithrombotic and anticoagulant activity in
      addition to its known antiproliferative properties. Because of the molecular
      characteristics and the dual nature of the pharmacologic action of PI-88, this
      agent represents an attractive pharmacologic agent for the control of thrombotic
      and proliferative disorders.

PMID- 11292192
TI  - Hemostatic and fibrinolytic status in patients with ovarian cancer and benign
      ovarian cysts: could D-dimer and antithrombin III levels be included as
      prognostic markers for survival outcome?
AB  - We determined the hemostatic and fibrinolytic status in 60 patients with ovarian
      cancer and benign ovarian cysts. Hypercoagulation, increased platelets, and
      enhanced fibrinolysis were seen in patients with preoperative ovarian cancer
      compared to patients with benign ovarian cysts. Enhanced thrombin generation,
      evidenced by increased F1+2 and decreased antithrombin III (ATIII) levels with
      further enhanced fibrinolysis by elevated D-dimer, was seen in advanced cancer.
      Ten ovarian cancer patients died within 13 months after diagnosis and another
      died at 24 months, all from advanced stage of cancer, except one from stage IC
      cancer who died at 11 months. The survival rates from the disease at 13 months
      and 24 months were 66.7% and 45%, respectively. Most of the patients had gone
      through the complete course of chemotherapy, and those patients still alive have
      been disease free between 13 and 42 months. No statistical relationships for the
      hemostatic parameters studied in ovarian cancer patients could be found between
      those who died and those still living 13 and 24 months after diagnosis, except
      for ATIII and D-dimer levels. Elevated D-dimer levels were associated with those
      who died within 13 and 24 months from the disease, and the decreased ATIII levels
      only reached statistical significance by 24 months. It could be suggested that
      these two parameters might be useful as systemic prognostic markers in survival
      outcome from the disease for the first 24 months in advanced ovarian cancer, in
      addition to the known correlation with the International Federation of Gynecology
      and Obstetrics stage.

PMID- 11292193
TI  - Global anticoagulant effects of a novel sulfated pentomanan oligosaccharide
      mixture.
AB  - PI-88 is a potent antiproliferative agent, which is developed for various
      indications in cancer. This agent is obtained from yeast fermentation and is
      primarily composed of pentamannose and tetramannose oligosaccharide units. PI-88
      is capable of producing anticoagulant effects, which are mediated by heparin
      cofactor II. The purpose of this study was to determine the anticoagulant
      properties of PI-88 in native whole blood, freshly drawn from human volunteers,
      supplemented with PI-88 at various concentrations (0-100 microg/mL). Whole blood
      activated clotting time (ACT) was measured using Hemochron instruments. PI-88
      produced a strong anticoagulant effect at 100 microg/mL (479.0+/-59.5 sec). This
      anticoagulant effect was comparable to that observed in interventional cardiology
      and open-heart surgery. At the lower level, PI-88 produced concentration
      dependent effects on ACT. Using thromboelastographic techniques (TEG), the effect
      of PI-88 was measured in terms of various parameters. PI-88 produced potent
      anticoagulant effects in the TEG studies. At the concentration of 25 microg/mL,
      it produced a complete anticoagulant effect in whole blood. Whole blood samples
      supplemented with PI-88 showed a concentration-dependent decrease in the
      generation of various markers of clotting activation. These results clearly
      suggest that PI-88 exerts an anticoagulant effect in whole blood. Because of the
      low-molecular-weight nature and a novel mechanism of action, this new drug may be
      considered for further development, particularly in cancer patients.

PMID- 11292194
TI  - Effect of bezafibrate on soluble adhesion molecules and platelet activation
      markers in patients with connective tissue diseases and secondary hyperlipidemia.
AB  - We evaluated the plasma concentrations of soluble adhesion molecules, platelet
      activation markers, and platelet-derived microparticles (PMPs) in patients with
      connective tissue diseases who had secondary hyperlipidemia caused by long-term
      steroid administration (n = 22) before and after treatment with bezafibrate.
      There were differences in levels of platelet activation markers both before and
      after treatment (platelet CD62p: 15.11+/-2.03 vs 10.38+/-8.53%, P < 0.05;
      platelet CD63: 12.12+/-9.17 vs 9.90+/-7.20%, P < 0.05). There were also
      differences in the levels of PMPs and soluble adhesion molecules both before and
      after treatment (PMP: 514+/-273 vs 401+/-201 /10(4) platelet. P < 0.05; soluble
      vascular cell adhesion molecule-1: 724+/-191 vs 666+/-157 ng/mL, P < 0.01). After
      6 months of treatment, serum lipid concentrations were reduced by 9% for total
      cholesterol (TC) and 32% for triglyceride (TG). The level of PMPs, activated
      platelets, and soluble adhesion molecules were all significantly decreased after
      treatment with bezafibrate. These findings suggest that bezafibrate may be useful
      for inhibiting both PMP-dependent and -independent vascular damage in patients
      with connective tissue diseases complaining of secondary hyperlipidemia.

PMID- 11292195
TI  - Venous thromboembolism in young patients from western India: a study.
AB  - The goal of this article is to study the association of known markers of
      thrombophilia with venous thrombosis in young patients (< 45 years) from the
      Western part of India. A prospective study of 432 patients (252 males and 180
      females, age 1-45 years) was conducted between 1994 and 2000 (6 years). The
      diagnosis was confirmed in all the patients by ultrasound with Doppler or by a
      computed tomograph (CT) scan of the brain with or without contrast depending on
      the case. Detailed clinical examination, and family history was taken to
      establish recurrent thrombosis and familial occurrence of thrombosis. The markers
      studied were protein C, protein S, antithrombin (AT) III, factor V Leiden
      mutation, prothrombin gene G20210A polymorphism, and the thermolabile MTHFR
      variant C677T polymorphism, using appropriate techniques. Lupus inhibitor was
      tested in the first 72 patients using Dilute Russel Viper Venom Time (DRVVT)
      test, and anticardiolipin antibodies were tested by enzyme-linked immunosorbent
      assay. Protein C, protein S, and AT III deficiency was detected in 9.5%, 6.5%,
      and 2.6%, respectively, among the patients. Anticardiolipin antibody was present
      in 9.9% of the patients, whereas lupus anticoagulant was present in 8.3% of
      patients; factor V Leiden mutation was detected in 3% of patients; thermolabile
      variant of MTHFR C677T polymorphism was present in 14.9% of patients with 1.2%
      homozygotes. Prothrombin G20210A polymorphism was not detected in any sample in
      this population. One hundred and four patients of 432 (24.9%) had recurrent
      attacks of thrombosis without any proximate precipitating cause, whereas 7.5 % of
      the patients had another close member of the family with a history of deep venous
      thrombosis. Eighty-six members from 28 families (out of 32 families giving family
      history of thrombosis) were investigated and found to have protein C and protein
      S deficiency in seven each; factor V Leiden was present in 6, and MTHFR C677T
      polymorphism was present in 5 cases. Hence, 25 of 86 members (28%) from the
      family of patients with familial history deep venous thrombosis had positive
      markers for thrombophilia. Thus, we could show that in young patients presenting
      with thrombosis, at least 34% of them had a demonstrable cause for thrombophilia.
      Prothrombin gene polymorphism G20210A seems to be nonexistent in our population
      and AT III deficiency also appears to be low compared to other markers of
      thrombophilia. There is a high prevalence of variant MTHFR C677T in our series,
      but the incidence of MTHFR C677T in our general population is also high. Hence,
      the significance of this finding in our cases of deep venous thrombosis remains
      to be seen, but we did not see any homozygotes when we tested 70 randomly
      selected asymptomatic persons, whereas in the present series, 1.8% of the
      patients had homozygosity for the MTHFR C677T polymorphism.

PMID- 11292196
TI  - Spontaneous cervical epidural hematoma associated with oral anticoagulant
      therapy.
AB  - A 54-year-old woman who was on anticoagulant treatment with acenocoumarol for a
      mitral prothesis developed a cervical spinal epidural hematoma, probably
      triggered by coughing fits together with supratherapeutic anticoagulation.
      Because of the subacute evolution of the hematoma, it was not diagnosed until the
      patient was admitted to the hospital with profuse hemorrhages. Given the subacute
      nature of the hematoma, along with the favorable evolution, conservative
      treatment with dexamethasone was decided upon, and it was resolved with almost no
      sequelae. This unusual clinical entity definitely should be suspected in patients
      on anticoagulants who complain of severe localized neck pain, most often with
      radicular irradiation.

PMID- 11292197
TI  - Plasma and platelet von Willebrand factor abnormalities in patients with uremia:
      lack of correlation with uremic bleeding.
AB  - Chronic renal failure often is associated with abnormal bleeding that may
      represent an important complication of this disorder. The hemorrhagic tendency
      currently is attributed to altered primary hemostasis, mainly platelet
      dysfunction. However, von Willebrand factor (vWF) also seems to be involved, even
      though the nature of its abnormalities is still controversial. To gain insight
      into the role of vWF in determining uremic bleeding, we studied 11 patients with
      stable, chronic renal failure. We found a significant increase in plasma factor
      VIII (FVIII), vWF:antigen (Ag), and vWF:ristocetin cofactor (Rco) levels,
      associated with a mean decrease in platelet vWF:Ag. Plasma vWF multimer pattern
      was characterized by increased representation of all oligomers in all patients,
      but five patients also showed a slight decrease in large vWF multimers. In
      addition, platelet vWF multimer pattern displayed a decrease in all components,
      especially those with high molecular weight. Despite normal bleeding time,
      collagen-induced platelet aggregation was defective in almost all patients,
      whereas vWF collagen binding capacity was normal. The levels of glycocalicin, the
      circulating fragment of glycoprotein Ib-IX, the major platelet vWF receptor, were
      also normal. In six patients who also were studied after initiation of dialysis,
      collagen-induced platelet aggregation was impaired further. Moreover, plasma vWF,
      and especially FVIII levels, were increased additionally, in association with a
      normalized platelet vWF content and an improved vWF multimer pattern. The results
      suggest that vWF abnormalities are present in uremia. Moreover, thrombopathy
      caused by impaired collagen-induced platelet aggregation is constantly present
      and apparently not improved by dialytic treatment.

PMID- 11292198
TI  - Lung scintigraphy and helical computed tomography for the diagnosis of pulmonary
      embolism: a meta-analysis.
AB  - To assess the diagnostic value of lung scintigraphy and helical computed
      tomography (hCT) in patients with suspected pulmonary embolism (PE), all English
      language articles that described lung scintigraphy and hCT in patients with
      suspected PE were retrieved. Articles were assessed for strength of methodology,
      based on nine a priori-defined criteria. Parameters of diagnostic accuracy and
      results of management studies were calculated and evaluated. Lung scintigraphy is
      diagnostic in approximately 50% of patients with suspected PE. A normal perfusion
      scan has a chance of recurrent PE in two of 693 patients (0.3%; 95% CI: 0.2-0.4%;
      fatal in 0.15%). A high-probability lung scan is correlated with angiographically
      proven PE in 308 of 350 patients (88%; 95% CI: 84-91%). Pulmonary embolism was
      proven in 385 of 1529 patients (25%; 95% CI: 24-28%) with a nondiagnostic lung
      scan. Helical CT studies were compared with angiography and lung scintigraphy in
      1171 patients, with a prevalence of PE of 39%. The sensitivity and specificity of
      hCT was 283/320 (88%; 95% CI: 83-91%) and 374/408 (92%; 95% CI: 89-94%),
      respectively. Only one prospective management study using hCT was available. In
      patients in whom anticoagulants were withheld based on a normal hCT study,
      recurrent thromboembolic events occurred in six of 109 patients (5.5%; 95% CI: 2
      12%), with one fatality (1%; 95% CI: 0.02-4.3%). Lung scintigraphy is evaluated
      extensively and yields a diagnostic result in 50% of patients. Helical CT has
      similar positive predictive value to a high-probability lung scan. However, the
      exact role of hCT in the management of patients with suspected PE needs to be
      determined in prospective studies.

PMID- 11292199
TI  - Carboxypeptidase U at the interface between coagulation and fibrinolysis.
AB  - In 1988, Hendricks et al. first reported on the presence of carboxypeptidase U (U
      refers to the unstable nature of the enzyme) in human serum. One decade later,
      the importance of carboxypeptidase U (CPU) in the regulation of fibrin clot
      dissolution is well documented. CPU circulates in plasma as an inactive zymogen,
      proCPU, that is converted to its active form during coagulation and fibrinolysis.
      CPU cleaves off C-terminal lysine residues exposed on fibrin partially degraded
      by the action of plasmin. Because these C-terminal lysine residues are important
      for upregulating the fibrinolytic rate, CPU thus slows down fibrinolysis.

PMID- 11292200
TI  - Clustered pulmonary nodules: highly suggestive of benign disease.
AB  - Thirty-one adult patients with a cluster of small, noncalcified, pulmonary
      nodules identified on chest computed tomography (CT) examinations were studied
      retrospectively. Pathology revealed an infectious/inflammatory etiology in all
      cases in which a surgical resection of the involved lung was performed. None of
      the patients in our study group showed evidence of malignancy in the region of a
      cluster of pulmonary nodules over the follow-up period. The authors conclude that
      an isolated cluster of small pulmonary nodules is strongly suggestive of benign
      disease. Although exceptions may rarely occur, most cases represent incidental
      infectious or inflammatory disease.

PMID- 11292201
TI  - Sternal dehiscence in patients with and without mediastinitis.
AB  - The authors compared patients with sternal dehiscence (SD) with and without
      mediastinitis with respect to: 1) time interval from surgery to diagnosis; and 2)
      frequency of sternal wire abnormalities on chest radiographs (CXR). Using a
      hospital information system to identify all patients with a diagnosis of SD from
      January 1993 through April 1999, the authors obtained clinical data by performing
      a retrospective chart review. For each patient, a CXR from the date of diagnosis
      of SD was retrospectively compared with the first postoperative CXR to assess for
      sternal wire displacement, rotation, and disruption. The timing of sternal wire
      alterations was correlated with clinical findings of SD or mediastinitis. The
      authors found that sternal wire abnormalities are evident radiographically in the
      majority of SD patients with and without mediastinitis; there is no significant
      difference in the frequency of sternal wire abnormalities between these two
      subgroups. Patients with SD and mediastinitis generally present later in the
      postoperative period than patients with isolated dehiscence.

PMID- 11292202
TI  - A Web-based anatomic atlas.

PMID- 11292203
TI  - Sarcoidosis presenting as an enlarging solitary pulmonary nodule.
AB  - Sarcoidosis is generally not considered in the differential diagnosis of solitary
      pulmonary nodules. We recently encountered a case in which preoperative awareness
      of this presentation of sarcoidosis allowed a limited pulmonary resection with
      resultant lower morbidity and potential preservation of lung function to be
      performed. Although rare, sarcoidosis should be considered in the differential
      diagnosis of solitary pulmonary nodules.

PMID- 11292204
TI  - Supernumerary intrathoracic ribs: imaging features of two cases.
AB  - Intrathoracic supernumerary ribs are a rare congenital abnormality. The chest
      radiography and computed tomographic findings (including 3D reconstruction) of
      two cases are presented with a brief review of the literature.

PMID- 11292205
TI  - Silicoproteinosis: high-resolution CT and histologic findings.
AB  - The high-resolution CT findings of silicoproteinosis consist of numerous
      bilateral centrilobular nodular opacities, focal ground glass opacities, and
      patchy areas of consolidation. These findings reflect the presence of intra
      alveolar accumulation of proteinaceous material.

PMID- 11292206
TI  - Notes from the 2000 annual meeting of the Korean Society of Thoracic Radiology.

PMID- 11292207
TI  - Mixed infiltrative and obstructive disease on high-resolution CT: differential
      diagnosis and functional correlates in a consecutive series.
AB  - Fourteen of 400 consecutive patients having high-resolution computed tomography
      (HRCT) with expiratory images showed findings of infiltrative lung disease on
      inspiratory HRCT and air trapping on expiratory CT. Diagnoses included
      hypersensitivity pneumonitis, sarcoidosis, atypical infection, and pulmonary
      edema. The extent of infiltrative abnormalities and air trapping were correlated
      with pulmonary function tests (PFT) in 11 patients. PFT indicated a mixed pattern
      in five, an obstructive pattern in three, and a restrictive pattern in three.
      Forced expiratory volume (FEV) in 1 second/forced vital capacity (FVC) correlated
      significantly with the extent of air-trapping (r = 0.60; p = 0.05). The extent of
      infiltrative abnormalities correlated significantly and negatively with forced
      vital capacity (r = -0.82, p = 0.002), FEV1 (r = -0.59, p = 0.05), total lung
      capacity (TLC) (r = -0.67, p = 0.05), and DLCO (r = -0.75, p = 0.02). Findings of
      lung infiltration on inspiratory HRCT scans and air trapping on expiratory CT
      correlated respectively with PFT measures of restrictive and obstructive lung
      disease.

PMID- 11292208
TI  - Utility of high resolution computed tomography in predicting bronchiolitis
      obliterans syndrome following lung transplantation: preliminary findings.
AB  - This study was undertaken to evaluate the efficacy of high resolution computed
      tomography (HRCT) in predicting the development of bronchiolitis obliterans
      syndrome (BOS) in lung transplant recipients. Fifty lung transplant patients who
      were clinically stable and without evidence of BOS were evaluated for the
      presence of four HRCT features reported to be associated with bronchiolitis
      obliterans: mosaic attenuation on inspiratory CT (mosaic perfusion), mosaic
      attenuation on expiratory CT (air trapping), bronchiectasis, and tree-in-bud
      opacities. CT exams were part of an annual surveillance process with the hope of
      predicting subsequent development of BOS. Diagnosis of BOS was made in 9 of 50
      patients as indicated by a fall in FEV1 of greater than 20% of a stable baseline.
      None of the radiographic features associated with clinically established BOS were
      both sensitive and specific in the prediction of BOS. Air trapping demonstrated
      moderate sensitivity (56%, 5/9) and moderate specificity (76%, 35/46) for
      prediction of BOS in the year following the CT exam. Bronchiectasis, the most
      reliable indicator of the presence of BOS was a poor predictor of subsequent BOS
      with an 11% (1/9) sensitivity but had high specificity (96%, 44/46). No high
      resolution CT features accurately predicted the development of BOS.

PMID- 11292209
TI  - Further reduction of radiation dose in helical CT for lung cancer screening using
      small tube current and a newly designed filter.
AB  - A new aluminum filter, 5.8 mm thick at the center, was designed. The effective
      energy, exposure dose, absorbed dose, and noise were measured by using low-dose
      technique, very low-dose technique with a conventional filter, and very low-dose
      technique with a new filter on a chest phantom. Accuracy of very low-dose
      computed tomography (CT) with a new filter was compared against standard helical
      CT in 40 patients and against chest radiography in 35 patients. Effective
      energies were 42.6 keV and 51.6 keV at a conventional filter and the new filter,
      respectively. Compared against 20mA with a conventional filter, exposure dose was
      reduced by 17%, and absorbed dose was equivalent, at 30 mA with the new filter.
      Noise was improved by 9%. Compared with standard helical CT, the sensitivity,
      specificity, and accuracy of very-low-dose helical CT were 100%, 88%, and 95%,
      respectively. Very-low-dose helical CT was found to be significantly superior to
      chest radiography in the detection of lung cancers. Using a smaller tube current
      and an appropriate filter allows a further reduction in radiation dose in helical
      CT for lung cancer screening.

PMID- 11292210
TI  - FDG-PET imaging in patients with paraneoplastic syndromes and suspected small
      cell lung cancer.
AB  - Paraneoplastic syndromes may be the presenting clinical manifestation of small
      cell lung cancer. In some cases, however, confirming the diagnosis can be
      difficult because findings on conventional imaging studies can be subtle or
      nonspecific. This study examined the utility of fluoro-2-deoxy-glucose positron
      emission tomography (FDG-PET) in identifying clinically suspected small cell lung
      cancer in patients with paraneoplastic syndromes. FDG-PET appears to be very
      useful in localizing suspected small cell lung cancer in patients presenting with
      paraneoplastic syndromes.

PMID- 11292211
TI  - Pulmonary involvement in mixed connective tissue disease: high-resolution CT
      findings in 41 patients.
AB  - The objective of this study was to describe the pulmonary abnormalities on high
      resolution computed tomography (CT) in patients with mixed connective tissue
      disease (MCTD). The study included 41 patients who met the diagnostic criteria
      for MCTD and showed abnormal findings on high-resolution CT. The presence,
      extent, and distribution of various high-resolution CT findings were evaluated.
      The predominant abnormalities included areas of ground-glass attenuation (n =
      41), subpleural micronodules (n = 40), and nonseptal linear opacities (n = 32).
      Other common findings included peripheral predominance (n = 40), lower lobe
      predominance (n = 39), intralobular reticular opacities (n = 25), architectural
      distortion (n = 20), and traction bronchiectasis (n = 18). Less common findings
      included honeycombing, ill-defined centrilobular nodules, airspace consolidation,
      interlobular septal thickening, thickening of bronchovascular bundles, bronchial
      wall thickening, bronchiectasis, and emphysema. Pulmonary involvement of MCTD is
      characterized by the presence of ground-glass attenuation, nonseptal linear
      opacities, and peripheral and lower lobe predominance. Ill-defined centrilobular
      opacities were uncommonly seen.

PMID- 11292212
TI  - Unilateral pulmonary edema after talc pleurodesis.
AB  - Talc is commonly given after drainage of the pleural space to create pleural
      symphysis. Recognized complications of pleural drainage followed by talc
      pleurodesis include reexpansion pulmonary edema, pneumonia, and adult respiratory
      distress syndrome. This report describes a complication of talc pleurodesis that
      appears not to have been appreciated previously. Chest radiographs obtained
      before and after talc pleurodesis were evaluated in a total of 108 patients in
      three groups; 89 of these patients were receiving palliative therapy for
      malignant pleural effusion. Approximately 16% of the 108 patients developed a
      transient interstitial process in the lung ipsilateral to the treated pleural
      space. The recognized complications are inadequate to account for these
      radiographic findings. Other interstitial diseases such as hydrostatic pulmonary
      edema and lymphangitic carcinomatosis also are not adequate explanations. The
      observed complication is most likely the result of endothelial damage leading to
      a capillary leak type of pulmonary edema.

PMID- 11292213
TI  - Do cognitively normal children with epilepsy have a higher rate of injury than
      their nonepileptic peers?
AB  - The objective of this study was to determine if cognitively normal children with
      epilepsy have higher accidental injury rates than their age- and sex-matched
      friends without epilepsy and what factors may predict this. Patients 5 to 16
      years old, with a developmental quotient >70, without major motor or sensory
      impairments, with a 1-year history of epilepsy and who either had a seizure or
      had been on antiepileptic drugs within the past year, were identified from the
      pediatric neurology database of the Royal University Hospital. Twenty-five of 31
      cases and their best friend controls agreed to participate. Seizure-related
      factors including type, duration, frequency, timing, date of diagnosis,
      antiepileptic drug initiation and discontinuation, and specific types and total
      antiepileptic drugs used were assessed by interview. Questionnaires about
      accidental injury including type, number, severity, and, if applicable, injuries
      resulting from seizures, as well as general safety practices, activity
      restrictions, and presence of attention-deficit hyperactivity disorder, were
      completed by cases and controls. No significant differences in injury numbers
      (specific types or total) or severity were found, although a small number of
      epileptic children were very predisposed to injury. Seizure-related factors did
      not predict injury in cases. Safety practices were similar, and restrictions in
      cases were not excessive. Children with attention-deficit hyperactivity disorder
      had a higher injury rate, both in cases and controls. Cognitively normal children
      with epilepsy do not have a higher injury rate than their nonepileptic peers. If
      consciousness is impaired in seizures, extra supervision for swimming and bathing
      and restricted climbing heights are suggested. All other safety restrictions for
      epileptic children should follow those appropriate to nonepileptic children to
      allow a normal lifestyle.

PMID- 11292214
TI  - Encephalopathy associated with respiratory syncytial virus bronchiolitis.
AB  - Respiratory syncytial virus is an extremely common cause of childhood respiratory
      infections resulting in significant morbidity and mortality. Although apnea is a
      well-known complication in young infants with respiratory syncytial virus
      bronchiolitis, the encephalopathy associated with this infection is not well
      recognized. Our study reveals an incidence of encephalopathy of 1.8% in a total
      of 487 patients with respiratory syncytial virus bronchiolitis studied over a
      period of almost 4 years. Seizures were the presenting complication. Based on our
      study of a cohort of children with respiratory syncytial virus bronchiolitis, we
      believe that neurologic complications, although relatively uncommon, represent a
      significant component of this common childhood illness. Furthermore, respiratory
      syncytial virus has been shown to release several mediators that could directly
      or indirectly be neurotoxic and induce an encephalopathy associated with the
      respiratory illness.

PMID- 11292215
TI  - Benign myoclonus of early infancy: an imitator of West's syndrome.
AB  - Benign myoclonus of early infancy is a rare condition characterized by
      nonepileptic spasms that may resemble the epileptic spasms seen in West's
      syndrome. The spells in benign myoclonus of early infancy begin before age 1 year
      and are self-limited. The electroencephalogram (EEG) is invariably normal, and
      neurologic development is not affected. West's syndrome is characterized by
      infantile spasms that appear before 1 year of age, an abnormal EEG with
      hypsarrhythmia, and a poor prognosis. We describe six infants who presented for
      evaluation of clusters of head, trunk or extremity spasms, eye blinking, brief
      jerking of upper extremities or trunk, and head nodding episodes. In most, a
      presumptive diagnosis of West's syndrome was made prior to the referral. One
      infant had been placed on valproate. Routine EEG recordings or prolonged video
      EEG monitoring were normal both during and between episodes. After the negative
      evaluations, the diagnosis of benign myoclonus of early infancy was made in each
      infant. Subsequently, no infant was treated with anticonvulsants. Follow-up
      revealed complete resolution of the episodes in all children within 2 weeks to 8
      months of onset. All had normal neurologic development. Based on our cases and
      review of the literature, the prognosis for this disorder is excellent. Care
      should be taken to recognize this rare entity and avoid unnecessary and
      potentially harmful antiepileptic therapy.

PMID- 11292216
TI  - Use of botulinum toxin type A in pediatric patients with cerebral palsy: a three
      center retrospective chart review.
AB  - Over the last several years, botulinum toxin type A has gained widespread use for
      the management of focal spasticity in children with cerebral palsy. To assess the
      current patterns of botulinum toxin type A use in the clinical setting, the dose,
      muscles injected, age at injection, and interval between injections of botulinum
      toxin type A treatments were examined in a retrospective chart review of children
      with cerebral palsy (N = 270) over a 2-year period at three major treatment
      centers. The average dose of botulinum toxin type A across the three centers
      ranged from 7.7 to 10.8 U/kg body weight, and the average total amount of
      botulinum toxin type A injected at a single visit ranged from 154 to 205 U. The
      majority of botulinum toxin type A injections were to the muscles to the lower
      limbs. The average age at first injection was 6.2 years, and the average interval
      between injections ranged from 134 to 199 days.

PMID- 11292217
TI  - Acute cognitive effects of nonconvulsive difficult-to-detect epileptic seizures
      and epileptiform electroencephalographic discharges.
AB  - This study compares the acute cognitive effects of short nonconvulsive seizures
      with the effects of interictal epileptiform electroencephalographic (EEG)
      discharges in children. The study is a prospective, standardized, nonrandomized,
      and open clinical comparative study. Eligible patients were included when they
      had (a) unclear seizures and fluctuations in cognitive performance and (b)
      frequent epileptiform EEG discharges in a recent EEG. All children were assessed
      with EEG/video (Brainlab) simultaneously with computerized neuropsychologic
      testing (FePsy) assessing motor speed/alertness, mental speed/attention, and
      memory function. Eleven patients with short nonconvulsive seizures during
      cognitive testing were included and compared with 11 matched patients with
      interictal epileptiform EEG discharges during cognitive testing but without
      seizures. Patients included in both groups had a reconfirmed diagnosis of
      epilepsy. Cognitive performance for both groups was compared. Statistical
      analysis showed significant correlations between the number of seizures (during
      cognitive testing) and impaired alertness and between the duration of the ictal
      period and memory impairment. Interictal epileptiform EEG discharges do not have
      an additional independent effect on cognitive function. The results demonstrate
      the accumulating cognitive effect of seizures and illustrate that frequent
      seizures, even when these are short in duration and with subtle symptomatology,
      can have a substantial impact on daily life and can lead to state-dependent
      learning impairment. Alertness and short-term memory appeared to be the functions
      that are most vulnerable for the acute effects of seizures.

PMID- 11292218
TI  - Language dominance in children as determined by magnetic source imaging and the
      intracarotid amobarbital procedure: a comparison.
AB  - This study evaluated the validity of data derived from magnetic source imaging
      regarding hemispheric dominance for language in children and adolescents with
      intractable seizure disorder by comparison with results of the intracarotid
      amobarbital procedure. Functional imaging of the receptive language cortex using
      a whole-head neuromagnetometer was performed in 19 consecutive epilepsy patients,
      ages 8 to 18 years, who also underwent the intracarotid amobarbital procedure.
      During magnetic source imaging recordings, patients engaged in a continuous
      recognition memory task for words in visual and auditory modalities. This task
      has previously been shown to be valid for the purpose of lateralization and
      localization of language cortex in adult epilepsy patients who undergo the
      intracarotid amobarbital procedure and intraoperative language mapping allowing
      confirmation of magnetic source imaging findings. Results indicated that language
      laterality indices formed for the intracarotid amobarbital procedure and magnetic
      source imaging procedures were highly correlated (R = .87). In addition, clinical
      judgments regarding cerebral dominance for language made by independent raters
      using the two methods were in excellent agreement. We conclude that magnetic
      source imaging is a promising method for determination of cerebral dominance for
      language in children and adults.

PMID- 11292219
TI  - Subspecialization in the care of children with neurodevelopmental disabilities.

PMID- 11292220
TI  - Anterior spinal artery syndrome in an adolescent with protein S deficiency.
AB  - The diagnosis of anterior spinal artery syndrome can be made with high accuracy
      by thorough clinical examination in combination with typical magnetic resonance
      imaging findings. Sudden onset of tetra- or paraparesis and dissociated sensory
      loss with bladder dysfunction are the leading clinical signs. We discuss clinical
      and radiologic findings in an adolescent presenting with anterior spinal artery
      syndrome. The laboratory results showed a hereditary protein S deficiency.

PMID- 11292221
TI  - Mitochondrial DNA depletion associated with partial complex II and IV
      deficiencies and 3-methylglutaconic aciduria.
AB  - We report a patient with mitochondrial DNA depletion, partial complex II and IV
      deficiencies, and 3-methylglutaconic aciduria. Complex II deficiency has not been
      previously observed in mitochondrial DNA depletion syndromes. The observation of
      3-methylglutaconic and 3-methylglutaric acidurias may be a useful indicator of a
      defect in respiratory chain function caused by mitochondrial DNA depletion.

PMID- 11292222
TI  - Melatonin replacement therapy in a child with a pineal tumor.
AB  - The case report of a child with the diagnosis of a pineal tumor and severe,
      chronic sleep disorder is reported. Due to treatment of her lesion, the nighttime
      melatonin secretion was markedly suppressed. For 4(1/2) years, she has been
      receiving oral melatonin, which has greatly improved her sleep, without any
      adverse effects. Sleep difficulties should be considered in the management of
      pineal lesions. Melatonin replacement therapy is beneficial for those patients
      who have deficient melatonin synthesis.

PMID- 11292223
TI  - Tumor-related epilepsy in children.
AB  - A 10-year retrospective review of 15 children with cerebral tumors and seizures
      was conducted to study the factors responsible for delay in the diagnosis of
      tumors and to assess outcome following surgery. Mean duration of seizures prior
      to surgery was 37 months. Ninety-three percent had no focal neurologic deficits.
      Head computed tomography was abnormal in 64%, whereas magnetic resonance imaging
      was abnormal in all patients. Electroencephalography showed focal abnormalities
      ipsilateral to the tumor in 73%. There was no surgical mortality. Eighty percent
      were seizure free or had rare seizures following surgery. Factors contributing to
      a delayed diagnosis of the brain tumor included a nonfocal neurologic examination
      and delay in obtaining an appropriate neuroimaging study. We believe that head
      magnetic resonance imaging should be the investigation of choice in partial
      epilepsies.

PMID- 11292224
TI  - Narcolepsy in a 12-month-old-boy.
AB  - Narcolepsy, although frequently beginning in childhood, is usually diagnosed in
      young adults. The diagnostic symptoms of narcolepsy are usually less typical in
      the young child, and sleep studies have not been standardized. We present a 12
      month-old child with symptoms typical for narcolepsy who shows improvement with
      nonpharmacologic narcolepsy therapy.

PMID- 11292225
TI  - Prolonged treatment of refractory status epilepticus in a child.
AB  - Barbiturate anesthesia, which is commonly used for refractory status epilepticus,
      is an effective treatment, but with many significant complications. The
      relationship between the duration of this extreme therapy and the ultimate
      outcome of refractory status epilepticus has not been well studied. We report a 7
      year-old girl who presented with refractory status epilepticus secondary to
      presumed encephalitis with a focal lesion on cranial magnetic resonance imaging.
      She was treated for 70 days with high-dose antiepileptic drugs and recovered with
      a residual seizure disorder. This case suggests that, if the status epilepticus
      is due to a reversible cause such as encephalitis, neurologic recovery may occur
      despite this very prolonged course of extreme therapy.

PMID- 11292226
TI  - Additional case of Marden-Walker syndrome: support for the autosomal-recessive
      inheritance adn refinement of phenotype in a surviving patient.
AB  - In this report, we present a 14-year-old girl, born to consanguineous parents,
      who presented with severe mental retardation, hypotonia, short stature, and
      congenital joint contractures. The craniofacial features were scaphocephaly,
      thin/long and immobile face, marked hypoplasia of the midface, temporal
      narrowness, blepharophimosis, palpebral ptosis, and strabismus. The combination
      of such a distinctive craniofacial appearance and psychomotor retardation allows
      us to recognize a new case of the Marden-Walker syndrome. Our patient represents
      one of the rare cases in which consanguineous mating supports the autosomal
      recessive pattern of inheritance of this condition. Furthermore, through refining
      the phenotype of a surviving patient, this report may contribute to a better
      recognition of this disorder in older affected children.

PMID- 11292227
TI  - Prolonged but reversible respiratory failure in a newborn with Prader-Willi
      syndrome.
AB  - A 29-week premature infant with severe central hypoventilation secondary to
      Prader-Willi syndrome required mechanical ventilation until 55 days of age. This
      disorder must be considered in the differential diagnosis of a premature infant
      who does not have primary lung disease but has significant hypotonia because the
      respiratory failure may require prolonged supportive care.

PMID- 11292228
TI  - Preventive therapy in pediatric migraine.
AB  - Preventive therapy for migraine headache includes identification of migraine
      precipitants, possible adjustments in lifestyle, appropriate management of acute
      headache, and, when necessary, the use of pharmacologic agents. There are no well
      controlled clinical trials with sufficient patient numbers to support the use of
      any agent in the prevention of migraine headache in children. Data on the use of
      amitriptyline and divalproex sodium in open-label studies suggest that these
      agents may be efficacious. The mechanism of action for these agents is unknown
      but may be related to the 5-hydroxytyptamine-2 (5-HT2) receptor antagonism or
      regulation of ion channels. A review of the pertinent literature on migraine
      prophylaxis in children is presented. Dosing guidelines are presented based on
      the limited data available and clinical experience.

PMID- 11292229
TI  - Developmental changes in cerebrospinal fluid concentrations of monoamine-related
      substances in patients with dentatorubral-pallidoluysian atrophy.
AB  - Using a Coulochem electrode array system, we investigated the developmental
      changes of monoamine-related substances in patients with dentatorubral
      pallidoluysian atrophy. The patterns observed in the developmental changes of
      tryptophan, tyrosine, homovanillic acid (HVA), 3-O-methyldopa, and 3-methoxy4
      hydroxyphenyl glycol (MHPG) in patients with dentatorubral-pallidoluysian atrophy
      are quite different from those in control subjects. These abnormal developmental
      changes in monoamine-related substances may be implicated in age-related
      differences in clinical symptoms of dentatorubral-pallidoluysian atrophy.

PMID- 11292230
TI  - Incidence of concussion in high school football players of Ohio and Pennsylvania.
AB  - Football injuries account for more concussions than any other sport in North
      America. A 1977 survey of high school football players in Minnesota found that
      19% of players reported at least one concussion (characterized by loss of
      awareness) during a season. These results have not been confirmed in subsequent
      studies. This study sought to estimate the incidence of concussion among high
      school football players in our region, establish the frequency of the most common
      symptoms, and determine the duration of subsequent restriction from participation
      in the sport. The athletic boards of area high schools distributed a three-page
      survey to 450 high school football players. Of the 450 surveys distributed, 234
      (52%) were returned, only 1 of which was excluded because of contradictory
      information. The incidence of concussion in football players was 47.2% (110/233,
      P < .001 versus a previously determined rate of 19%). Eighty-one of 233 players
      (34.9%) had multiple concussions. A total of 376 concussions were reported. The
      distribution of severity of the 376 reported concussive events was grade I,
      87.8%; grade II, 9.9%; and grade III, 2.4%. Only 12 athletes were required to
      stop play for one or more games. The incidence of high school football players
      sustaining a concussion is much higher than previously established. The majority
      of these are mild (grade I) concussions. Further research is needed since
      multiple low-grade concussions may incur cumulative neuropsychologic impairments.

PMID- 11292231
TI  - Melatonin for chronic sleep onset insomnia in children: a randomized placebo
      controlled trial.
AB  - To establish the efficacy of melatonin treatment in childhood sleep onset
      insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more
      than 1 year from chronic sleep onset insomnia, were studied in a double-blind,
      placebo-controlled study. The children were randomly assigned to receive either 5
      mg melatonin or placebo. The study consisted of a 1-week baseline, consecutively
      followed by a 4-week treatment period. After that period, treatment was continued
      if the parents wished so. The study's impact was assessed by measurements of
      lights-off time, sleep onset, and wake-up time, recorded in a diary (n = 33).
      Sleep onset was also recorded with an actigraph (n = 25). Endogenous dim light
      melatonin onset was measured in saliva (n = 27). Sustained attention was
      evaluated with the Bourdon-Vos reaction time test (n = 36). In the melatonin
      group, mean (95% CI) lights-off time advanced 34 (6-63) minutes, diary sleep
      onset 63 (32-94) minutes, actigraphic sleep onset 75 (36-114) minutes, and
      melatonin onset 57 (24 to 89) minutes; total sleep time increased 41 (19-62)
      minutes. In the placebo group, these parameters did not shift significantly. The
      change during the 4-week treatment period differed between the treatment groups
      significantly as to lights-off time, diary and actigraphic sleep onset, sleep
      duration, and melatonin onset. There were no significant differences between the
      treatment groups in the change of sleep latency, wake-up time, and sustained
      attention reaction times. Mild headache occurred in 2 children during the first 2
      days of the melatonin treatment. Eighteen months after the start of the trial, in
      13 of the 38 children who could be followed up, melatonin treatment was stopped
      because their sleep problem was solved and in 1 child because sleep was not
      improved. Twelve children used melatonin 5 mg, the other 1.0 to 2.5 mg. One child
      developed mild generalized epilepsy 4 months after the start of the trial. The
      results show that melatonin, 5 mg at 6 PM, was relatively safe to take in the
      short term and significantly more effective than placebo in advancing sleep onset
      and dim light melatonin onset and increasing sleep duration in elementary school
      children with chronic sleep onset insomnia. Sustained attention was not affected.

PMID- 11292232
TI  - Vacuolating megalencephalic leukoencephalopathy in 12 Israeli patients.
AB  - Leukodystrophy with macrocephaly as the main features of infantile
      neurodegenerative disease are characteristics of Canavan's disease, L-2
      hydroxyglutaric aciduria, type I glutaric aciduria, and Alexander's disease. Also
      occasionally described are occidental congenital muscular dystrophy, G(M)2
      gangliosidosis, metachromatic leukodystrophy, Krabbe's disease, and
      mucopolysaccharidosis. Since 1995, over 60 patients with a new syndrome,
      vacuolating megalencephalic leukoencephalopathy, have been described. The
      syndrome is characterized by macrocephaly, a slowly progressive clinical course
      of ataxia, spastic paraparesis, and seizure disorder with relatively spared
      cognition. Unlike other leukodystrophies with macrocephaly (except Alexander's
      disease), no metabolic marker has been found. We describe a similar group of 12
      patients from two different Jewish ethnic origins in whom consanguinity is
      prominent. These patients have neuroimaging features and magnetic resonance
      spectroscopy findings indicating that there is an initial increase in white
      matter edema with subsequent cystic formation. Consistent with loss of tissue in
      these areas, brain metabolites are reduced. The familial incidence in this group
      of patients is suggestive of autosomal-recessive inheritance.

PMID- 11292233
TI  - Different intracellular signals coupled to the antiproliferative action of
      aqueous crude extract from Larrea divaricata Cav. and nor-dihydroguaiaretic acid
      on a lymphoma cell line.
AB  - In this paper, we report the effect of standard NDGA, as compared to that of an
      aqueous extract of Larrea divaricata Cav., on BW 5147 lymphoma cell-line
      proliferation. To determine the mechanism of action, the effects of both on the
      level of intracellular cAMP, protein kinase C activity and calcium influx were
      studied. Moreover, the NDGA present in the aqueous extract of the plant was
      quantified. The aqueous extract and the standard NDGA showed antiproliferative
      action against these cells. While the antiproliferative activity of the aqueous
      extract was mediated by an increase in cAMP levels, and inhibition of PKC and
      calcium influx, the antiproliferative activity of NDGA was related only to the
      inhibition of PKC. Considering the amount of NDGA detected in the aqueous extract
      of the plant, at the concentrations analyzed in this case, antiproliferative
      activity of Larrea divaricata cannot be attributed to this compound, but could
      have an additive effect on the activity of other compounds.

PMID- 11292234
TI  - Hepatoprotective and anti-Helicobacter pylori activities of constituents from
      Brazilian propolis.
AB  - Propolis is a resinous hive product collected by honeybees from various plant
      sources. It is extensively used in food, beverage and in folk medicine for
      treating various ailments and reported to have broad spectrum of biological
      activities. The hepatoprotective activity of propolis and constituents from its
      MeOH extract belonging to various classes were tested on D-galactosamine (D
      GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary
      cultured mouse hepatocytes. The result indicated that hepatoprotective activity
      of alcoholic extract of tropical Brazilian propolis is mainly due to phenolic
      compounds including flavonoids. All the four isolated flavonoids possessed
      stronger inhibitory activity (IC50, < 25 microM) than silibinin (IC50, 39.6
      microM) on TNF-alpha-induced cell death. The labdane-type diterpenes isolated
      from the MeOH extract also exhibited significant hepatoprotective activity in the
      same experimental model. Moreover, the labdane-type diterpenes and some of the
      prenylated phenolic compounds possessed antibacterial activity against
      Helicobacter pylori.

PMID- 11292235
TI  - Anti-inflammatory activity of compounds isolated from the aerial parts of Abrus
      precatorius (Fabaceae).
AB  - Two triterpenoid saponins 1 and 2 isolated from the aerial parts of Abrus
      precatorius and their acetates derivatives, 3 and 4 have been tested for anti
      inflammatory activity using the croton oil ear model. All the compounds exhibited
      anti-inflammatory activity but the acetates showed greater inhibition than the
      parent compounds.

PMID- 11292236
TI  - Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by
      Harpagophytum extract SteiHap 69.
AB  - Harpagophytum procumbens (Devil's Claw) is often used in the supportive treatment
      of inflammatory and degenerative diseases of the skeletal system. Here we studied
      the anti-inflammatory properties of the Harpagophytum extract SteiHap 69 (Steiner
      Harpagophytum procumbens extract 69) on primary human monocytes, a useful model
      of peripheral inflammation. After eliminating lipopolysaccharides of bacterial
      origin, SteiHap 69 prevented the LPS-induced synthesis of tumour necrosis factor
      alpha (TNFalpha) in stimulated primary human monocytes in a dose-dependent
      manner. Harpagide and harpagoside had no effect on LPS-induced TNFalpha-release.
      Our data provides evidence that the Harpagophytum extract SteiHap 69 has anti
      inflammatory properties. Further studies are required in order to elucidate the
      molecular mechanism of Devil's claw anti-inflammatory effects.

PMID- 11292237
TI  - Activity of plant extracts on the respiratory burst and the stress protein
      synthesis.
AB  - Aqueous, methanol and dichloromethane extracts from Artemisia copa, Baccharis
      grisebachii, Baccharis incarum, Baccharis latifolia, Mutisia kurtzii and Pluchea
      sagittalis, plants used in the Traditional Medicine of South America, are studied
      for activity on the respiratory burst and the inducible heat shock protein of 72
      kD (hsp72) synthesis. Activity on the production of reactive oxygen species (ROS)
      and reactive nitrogen species (RNS), as well as on hsp72 synthesis was measured
      by flow cytometry in human neutrophils. Cells were stimulated using hydrogen
      peroxide, phorbol-12-myristate-13-acetate (PMA) or formyl-methionyl-leucyl
      phenylalanine (FMLP) for ROS generation, and sodium nitroprusside (SNP) or PMA in
      the presence of calmodulin inhibitor W-13 for RNS. The production of hsp72 was
      induced by heat, PMA, H2O2 and SNP. The best inhibitory activity was shown by the
      dichloromethane extracts of Baccharis grisebachii and Pluchea sagittalis that
      were active in all the assays. The aqueous extract of Pluchea sagittalis was also
      active in most assays. The aqueous extract from Mutisia kurtzii caused a clear
      increase of the hsp72 production and showed prooxidant activity.

PMID- 11292238
TI  - S-allyl cysteine reduces oxidant load in cells involved in the atherogenic
      process.
AB  - Oxidation of low-density lipoprotein (LDL) and activation of the pleiotropic
      transcription factor nuclear factor kappa B (NF-kappaB), are often the chemical
      and molecular alterations associated with the development of the atherosclerotic
      lesion. We have reported previously on the antioxidant properties of a garlic
      compound, S-allyl cysteine (SAC), and its ability to inhibit damage caused by
      oxidative stress in bovine endothelial cells. In this study, the antioxidant
      effects of SAC were further determined, using several in vitro assay systems.
      First, we determined the effect of SAC on Cu2+-induced oxidation of LDL. Varying
      concentrations of SAC were co-incubated with a standardized Cu2+/LDL solution,
      and LDL-oxidation was then ascertained by determining the formation of
      thiobarbituric acid reactive substances (TBARS). SAC inhibited LDL-oxidation at
      an optimum concentration of 1 mM. In another experiment, we determined the
      effects of SAC on oxidized-LDL (ox-LDL) activation of J774 murine macrophages and
      human umbilical vein endothelial cells (HUVEC). Cells were grown on 96-well
      plates, preincubated with SAC at 37 degrees C and 5% CO2 for 24 h, washed, and
      exposed to ox-LDL for 24 h. Levels of hydrogen peroxide (H2O2) were determined by
      a fluorometric assay. In both cell lines, SAC exhibited dose-dependent inhibition
      of H2O2 formation. We also studied the effects of SAC on NF-kappaB activation in
      HUVEC using tumor necrosis factor-a (TNF-alpha) or H2O2 as stimulators. Cells
      were grown in 75 cm2 flasks at 37 degrees C and 5% CO2 and were preincubated with
      SAC 24 h before stimulation with TNF-alpha or H2O2. Nuclear extracts were then
      prepared and NF-kappaB activation was determined using an electrophoretic
      mobility shift assay with a 32P-labeled probe. SAC exhibited dose-dependent
      inhibition of NF-kappaB activation. Our data suggest that SAC may act via
      antioxidant mechanisms to inhibit the atherogenic process.

PMID- 11292239
TI  - Search for potential angiotensin converting enzyme (ACE)-inhibitors from plants.
AB  - MeOH extracts, fractions and pure substances from Musanga cecropioides, Cecropia
      species and Crataegus oxyacantha /C. monogyna were screened by using an in vitro
      bio-assay based on the inhibition of Angiotensin Converting Enzyme (ACE), as
      measured from the enzymatic cleavage of the chromophore-fluorophore-labelled
      substrate dansyltriglycine into dansylglycine and diglycine. Phenolic acids
      showed no significant ACE-inhibition whereas flavonoids and proanthocyanidins
      demonstrated inhibitory activity at 0.33 mg/ml using this test system.

PMID- 11292240
TI  - Inhibitory effect of sulfated galactans from the marine alga Bostrychia montagnei
      on herpes simplex virus replication in vitro.
AB  - Sulfated polysaccharides exhibit many biological properties such as antiviral and
      anticoagulant activities. Herein, we report the antiviral activity of sulfated
      galactans extracted from the red sea-weed Bostrychia montagnei against herpes
      simplex virus types 1 (strain F and the thymidine kinase-deficient strains Field
      and B2006) and 2 (strain G). Two crude extracts obtained with cold and hot water
      as well as some fractions obtained by anion exchange chromatography, inhibited
      significantly the replication of the different strains of herpesviruses as
      determined by plaque reduction assays. The inhibitory effect of the compounds
      studied here took place only when they were added during the adsorption period.
      They were found to be highly selective antiviral substances, causing no
      impairment of Vero cell viability. Furthermore, they had no direct inactivating
      effect on virions by incubation in a virucidal assay. The antiviral activity
      could be correlated with the molecular weight and sulfate content of the
      polysaccharides. Although sulfated polysaccharides are generally endowed with
      anticoagulant properties, the results of the activated partial thromboplastin
      time and the thrombine time assays indicated that the natural sulfated
      polysaccharides from Bostrychia montagnei have very low anticoagulant activity,
      confirming that there is no relation between the antiviral and anticoagulant
      properties.

PMID- 11292241
TI  - Biological screening of selected medicinal Panamanian plants by radioligand
      binding techniques.
AB  - Nineteen plants from the Republic of Panama were selected by their traditional
      uses in the treatment of hypertension, cardiovascular, mental and feeding
      disorders and 149 extracts were screened using radioligand-receptor-binding
      assays. The methanol:dicloromethane extracts of the bark and leaves of Anacardium
      occidentale L., the leaves of Begonia urophylla Hook., the roots of Bocconia
      frutescens L., the stems and leaves of Cecropia cf.obtusifolia Bertol., the
      branches of Clusia coclensis Standl., the bark of Cochlospermum vitifolium
      (Willd.)Spreng., the roots of Dimerocostus strobilaceus Kuntze, the bark of
      Guazuma ulmifolia Lam., the leaves of Persea americana Mill. and the branches of
      Witheringia solanaceae L'Her. inhibited the [3H]-AT II binding (angiotensin II
      AT1 receptor) more than 50%. Only extracts of the roots of Dimerocostus
      strobilaceus Kuntze and the stems of Psychotria elata (Sw.) Hammel were potent
      inhibitors of the [3H] NPY binding (neuropeptide Y Y1 receptor) more than 50% and
      the ethanolic extracts of the leaves of Cecropia cf. obtusifolia Bertol., the
      leaves of Hedyosmum bonplandianum H.B.K., the roots of Bocconia frutescens L.,
      the stem of Cecropia cf. obtusifolia Bertol. and the branches of Psychotria elata
      (Sw.) Hammel showed high inhibition of the [3H] BQ-123 binding (endothelin-1
      ET(A) receptor) in a preliminary screening. These results promote the further
      investigation of these plants using the same assays.

PMID- 11292242
TI  - Biological screening of rain forest plot trees from Palawan Island (Philippines).
AB  - Study plots totaling 0.2 Ha were established in primary forest in the highlands
      of central Palawan Island, Philippines. Samples of various anatomical parts
      [typically leaf + twig (If/tw), stem bark (sb), and root (rt)] were collected
      from all tree species represented within the plots by individuals having a
      diameter at breast height > or = 10 cm. In all, 211 distinct samples were
      obtained from 68 tree species, representing 35 families (not including samples
      from 4 indeterminate species). Methanol extracts of these samples were tested in
      in vitro antiplasmodial, brine shrimp toxicity, and cytotoxicity assays. The
      following samples showed an IC50 < or = 10 microg/mL against either chloroquine
      sensitive or chloroquine-resistant clones of Plasmodium falciparum: Acronychia
      laurifolia (sb), Agathis celebica (lf/tw), Aglaia sp. 1 (sb), Aglaia sp. 2
      (lf/tw, rt), Bhesa sp. 1 (rt), Cinnamomum griffithii (lf/tw), Croton leiophyllus
      (rt), Dysoxylum cauliflorum (rt), Garcinia macgregorii (sb), Lithocarpus sp. 1
      (rt, sb), Meliosma pinnata ssp. macrophylla (lf/tw, rt), Myristica guatteriifolia
      (lf/tw), Ochrosia glomerata (rt, sb), Swintonia foxworthyi (lf/tw), Syzygium sp.
      1 (rt), Turpinia pomifera (rt), and Xanthophyllum flavescens (sb). Secondly,
      those samples which displayed > or = 50% immobilization of brine shrimp at 100
      microg/mL were: Acronychia laurifolia (lf/tw/fruit, rt, sb), Agathis celebica
      (lf/tw, sb), Aglaia sp. 1 (lf/tw), Alphonsea sp. 1 (rt), Ardisia iwahigensis
      (lf/tw), Arthrophyllum ahernianum (lf/tw, rt, sb), Castanopsis cf. evansii (rt),
      Cinnamomum griffithii (lf/tw, rt), Croton argyratus (lf/tw), C. leiophyllus
      (lf/tw, rt), Dysoxylum cauliflorum (fruit, lf/tw, rt), Euonymus javanicus (rt),
      Glochidion sp. 1 (rt), Polyosma sp. 1 (rt), Symplocos polyandra (rt), Timonius
      gammillii (sb), and Xanthophyllum flavescens (rt). Lastly, samples which
      exhibited an IC50 < or = 20 microg/mL against one or more of the cancer cell
      lines employed (LU1, KB, KB-V1, P-388, LNCaP, or ZR-75-1) include: Acronychia
      laurifolia (lf/tw/fruit, rt, sb), Aglaia sp. 1 (sb), Aglaia sp. 2 (rt), Alphonsea
      sp. 1 (rt), Ardisia iwahigensis (lf/tw, rt, sb), Astronia cumingiana (sb), Croton
      argyratus (lf/tw, rt, sb), C. leiophyllus (lf/tw, rt), Dimorphocalyx murina
      (lf/tw, rt, sb), Lithocarpus caudatifolius (rt, sb), Litsea cf. sibuyanensis
      (rt), Syzygium cf. attenuatum (rt, sb), S. confertum (sb), Ternstroemia
      gitingensis (rt), and Ternstroemia sp. 1 (rt, sb).

PMID- 11292243
TI  - Effects of an oriental herbal medicine, "Saiboku-to", and its constituent herbs
      on Compound 48/80-induced histamine release from peritoneal mast cells in rats.
AB  - Effects of a traditional oriental herbal medicine, "Saiboku-to" and its
      constituent herbs on Compound 48/80-induced histamine release from peritoneal
      mast cells in rats were investigated. Saiboku-to inhibited Compound 48/80-induced
      degranulation of and histamine release from the mast cells, suggesting that
      Saiboku-to not only possesses anti-histamine release effect from mast cells, but
      also contains active herbs with this effect. Significant inhibitions were found
      in 4 of 10 constituent herbs of Saiboku-to: Magnoliae Cortex, Perillae Herba,
      Bupleuri Radix and Hoelen. In the dose-response curves of the four herbs, the
      logarithmic linearity was observed for each herb, and 50% inhibitory
      concentration, the IC50 values, were calculated to be 56.8 microg/ml for
      Magnoliae Cortex, 175.8 microl/ml for Perillae Herba, 356.6 microg/ml for
      Bupleuri Radix, and 595.8 microg/ml for Hoelen. One mg/ml of Saiboku-to showing
      75% inhibition of Compound 48/80-induced histamine release level from mast cells
      contains 88.5 microg of Magnoliae Cortex (it was estimated from the dose-response
      curve that this dose inhibits 62.68% of the Compound 48/80-induced histamine
      release level), 58.8 microg of Perillae Herba (21% inhibition), 205.9 microg of
      Bupleuri Radix (35.24% inhibition), and 147.1 microg of Hoelen (11.15%
      inhibition). From these results, it is suggested that the anti-histamine release
      effect of Saiboku-to, which contains 10 herbs, may be due mainly to the effect of
      Magnoliae Cortex and the synergism of the 3 other herbs.

PMID- 11292244
TI  - Establishment of a mouse thymic epithelial cell line, IT-76MHC and a brief review
      on cultured thymic epithelial cells.
AB  - Interactions between thymocytes and thymic stromal cells are essential for
      thymocyte differentiation, but little evidence has been presented to directly
      show in vivo functions or interactions of the stromal cells. Among the stromal
      cells, the thymic epithelial cell has been considered to have profound effect on
      thymocyte differentiation and maturation. The calcium-depleted medium, originally
      developed for the culture of mouse epidermal cells, was applied for the culture
      of the mouse thymic epithelial cells, and successfully, an epithelial cell line,
      IT-76MHC was obtained from the mouse thymus. IT-76MHC cells were identified as
      distinct mouse thymic epithelial cells by 1/ mosaic-like arrangement, 2/ presence
      of well-developed desmosome and 3/ tonofilaments, 4/ positivity for cytokeratin,
      and 5/ induced expression of MHC class I and II by IFN-gamma treatment. IGF-1,
      IGF-2, oxytocin and vasopressin were also detected immunohistochemically in IT
      76MHC cells. Furthermore, the IT-76MHC thymic epithelial cells, when injected
      intrathymically in the allogeneic mouse, prolonged the survival of skin graft
      from the same donor strain that IT-76MHC cells were derived. These results
      demonstrate that the thymic epithelial cell line IT-76MHC produces modest
      thymocyte survival factors as well as a growth suppressor, and that IT-76MHC
      cells have the ability to induce transplantation tolerance probably through their
      expression of MHC class I and II molecules. Taken altogether, the IT-76MHC thymic
      epithelial cells have been proved to be useful tools to better understand the in
      vivo functions of thymic epithelial cells, and to gain a deep insight into their
      involvement in the critical selection process of thymocytes which still remains
      obscure. Finally and additionally, literatures so far reported on thymic
      epithelial cells in culture, especially lines and clones, are reviewed and their
      identity as well as their functions are discussed.

PMID- 11292246
TI  - Specialisation of thymic epithelial cells for positive selection of CD4+8+
      thymocytes.
AB  - Following their migration into the thymus, hemopoeitic stem cell precursors enter
      a complex developmental pathway involving proliferation, differentiation and
      alphabetaT-cell receptor (alphabetaTCR)-mediated selection procedures, in order
      to generate mature T-cell populations ready for export to the periphery. Thus, a
      critical stage during intrathymic T-cell development involves the generation of
      functionally mature CD4+8- and CD4-8+ cells from immature CD4+8- precursor
      thymocytes, a poorly understood process referred to as positive selection. While
      interactions between the alphabetaTCR and MHC-peptide complexes are known to be
      essential for the initiation of positive selection, additional unknown signals
      are also required. Using an in vitro reaggregate thymic organ culture system
      which allows comparison of the abilities of various cell types to induce
      maturation of CD4+8+ precursors, we provide evidence that both MHC-peptide
      complexes and specialised accessory molecules must be provided by thymic
      epithelium for efficient mediation of positive selection. Moreover, analysis of
      positive selection in the presence of thymic and non-thymic stromal cells
      expressing MHC class II molecules with the same limited peptide array suggests
      that this unique ability of thymic epithelium to mediate positive selection of
      CD4+8- cells is not solely due to presentation of a specialised peptide
      repertoire, but is dependent upon provision of specialised accessory
      interactions.

PMID- 11292245
TI  - Cellular and molecular interactions of thymus with endocrine organs and nervous
      system.
AB  - T-cell ontogenesis has been disclosed to depend on the interactions of thymus
      with endocrine glands and nervous system as follows: i/ Thymic deprivation not
      only impaired the immunological development but also brought about the dysgenesis
      of pituitary anterior lobe. Conversely, hypophysectomy resulted in thymus atrophy
      with the disturbed immune responses. ii/ Binding of pituitary acidophilic cell
      hormones to their receptors on thymus epithelial cells (TECs) augmented the
      release of thymic hormonal peptides (THPs) in vitro. iii/ Elevation of blood
      glucocorticoid level after stress caused atrophy of thymus cortex through double
      positive thymocyte apoptosis. Morpho-molecular alterations of cytoplasm preceded
      nuclear damage in the apoptotic thymocytes. iv/ Administration of thymosin to the
      streptozotocin-induced diabetic mice repressed mononuclear cell infiltration to
      the pancreatic islets. v/ Autonomic nerve fibers innervate thymic parenchyma.
      Binding of acetylcholines (Achs) to Ach receptors on TECs enhanced protein
      synthetic activity which seemed to connect with THP production. vi/ Thymectomy
      not only depressed the immune responses but also accelerated the reduction of
      leaming and memory ability with aging. The operation appears to disturb the brain
      adrenoceptor functions and to suppress the regulatory roles of hypothalamus to
      other nervous tissues. vii/ Several kinds of THPs, separated from the culture
      supernatant of TEC line by high performance liquid chromatography, showed a
      favorable effect on the thymocytes at different stage of differentiation and
      maturation. viii/ Thymosin, thymulin and THPs were capable of proliferating and
      differentiating thymocytes in vitro. However, the administration of each thymic
      product to the thymus-deprived animals could not restore from their "wasting
      disease". Since TECs are composed of a heterogeneous population, it would be one
      of essential ways for isolating "true thymus hormone" (TTH) to use the material
      which consists of functionally homogeneous subset of TECs. ix/ An additional
      grafting of pituitary gland to the thymus-grafted nude mice improved the
      disturbed T-cell ontogeny. Accordingly, the administration of "TTH" and pituitary
      acidophilic cell hormones might be more hopeful procedure for rescuing the thymus
      deprived animals from "wasting disease".

PMID- 11292247
TI  - A role for CD8 in limiting degeneracy of thymocyte selection.
AB  - The introduction of a soluble TCR (sTCR) recognizing class I major
      histocompatibility complex (MHC) in the fetal thymic microenvironment in vitro
      produces the selection of thymocytes with enhanced avidity for self class I MHC
      (8). The sTCR was supposed to impose enhanced avidity for self MHC at an early
      degenerate phase of TCR-driven selection. This could determine increased
      reactivity to self at later stages of differentiation when specificity of TCR
      ligand interaction augments and the effect of sTCR vanishes. This hypothesis was
      based on the observed deletion of CD4+8+ thymocytes upon upregulation of TCR and
      the increase in cell size of some CD8+ cells which are expanded in long-term
      fetal thymus organ cultures (FTOC) as well as in the periphery of adoptively
      transferred nude mice. Here we show that the developing alphabeta thymocyte which
      does not express CD8 at the cell surface has a selective advantage in FTOC with
      sTCR, thus suggesting that participation of CD8 in self peptide/MHC recognition
      confers specificity to T-cell selection and results in excessive signaling in
      thymocytes in spite of the presence of sTCR.

PMID- 11292248
TI  - T-T interaction during thymic selection.
AB  - During thymic development, immature thymocytes are selected through the
      interaction with self peptides loaded on self MHC molecules. Although there is a
      great deal of debates on how specifically thymocytes recognize self peptides
      during thymic selection, recent data suggest an important role of peptide
      diversity in selecting an adequate T-cell repertoire in the thymus. The findings
      that human T-cells, unlike mouse T-cells, express MHC class II molecules on their
      surfaces and can play as antigen presenting cells suggesting possible peripheral
      T-T interaction network has not been intensively studied so far. However, the
      facts that human thymocytes have surface expression of MHC class II molecules and
      thymocytes can be selected by thymocytes in in vitro re-aggregation culture
      system led us to propose a novel hypothesis - "T-T interaction during thymic
      selection". Our proposition is that peripheral T-T interaction through TCR
      derived peptides might reflect the selection process in the thymus and that T-T
      interaction also plays an important role in thymic selection. This review deals
      with our thymic T-T interaction hypothesis and its implications on human T-cell
      development.

PMID- 11292249
TI  - The thymus and the acute phase response.
AB  - The thymus is a primary lymphoid organ with both endocrine and immune functions.
      There is a large body of evidence indicating the existence of a complex
      neuroendocrine control of the thymus physiology. This is supported by the
      historic observation that the thymus becomes involuted during the response to
      stress. The thymus is dramatically affected by the acute phase response (APR), a
      systemic reaction to tissue injury and/or infection accompanied by profound
      neuroendocrine and metabolic changes. The APR comprises alterations in behavior,
      body temperature, and production and release of cytokines, particularly
      interleukin (IL)-1, IL-6 and TNFalpha, and glucocorticoids (GCs) and is
      characterized by suddenly increased production of so-called acute phase proteins
      (APPs). The stimulation of APR activates the hypothalamic-pituitary-adrenal (HPA)
      axis, resulting in the suppression of specific immunity, which might serve to
      protect the organism from adverse immune reactions; the immunostimulatory
      hormones (e.g., PRL, GH, IGF-1) are suppressed, whereas the production of APPs in
      the liver is stimulated by IL-6, catecholamines and GCs. The most striking effect
      of the latter on the immune system is the induction of apoptosis in the thymus.
      In concert with GCs, elevated levels of catecholamines also selectively suppress
      immune response mechanisms. APR may be regarded as an emergency response that
      represents a switch of the host defense from the adaptive immune response which
      is slow to develop and is commanded by the thymus and T-lymphocytes to a less
      specific, but more rapid and intense reaction. Here we discuss the
      immunoregulatory changes during the APR with a special emphasis on the role of
      thymus in this process.

PMID- 11292250
TI  - Clonal growth inhibition as a bioassay for thymosin alpha1: inactivation of
      Talpha1 by trifluroacetic acid.
AB  - Thymosin alpha1 (Talpha1) is an immune response modifying peptide isolated from
      thymus tissue. The synthetic peptide has been evaluated in clinical trials as an
      adjuvant to cancer chemotherapy, an enhancer of vaccine potency, and an anti
      viral for both hepatitis B and C. Among its multiple in vitro activities is the
      inhibition of the clonal growth of hepatitis B transfected hepatoblastoma cells.
      This assay was used to define the relationship between bioactivity and
      immunoactivity of Talpha1. Talpha1 was treated with 50% trifluoroacetic acid
      (TFA) for 1 hr to inactivate the peptide. Talpha1 heated at 90 degrees C or at
      room temperature maintained its bioactivity but TFA completely eliminated the
      activity in the bioassay. The TFA inactivated Talpha1 had a retention time on
      reverse-phase chromatography identical to bioactive Talpha1 but reduced
      immunoreactivity. In addition to demonstrating the utility of clonal growth as a
      bioassay, these studies demonstrate that immunoreactivity rather than retention
      time on HPLC may be a better predictor of bioactivity of synthetic Talpha1.

PMID- 11292251
TI  - Thymectomy-induced deterioration of learning and memory.
AB  - Age-associated immunodeficiency and cognitive deterioration are two predominant
      features of the aging process, but the mutual influences between them are not
      clear yet. Research on the neuroendocrine immunomodulation (NIM) network indicate
      reciprocal interactions between the neuroendocrine and the immune systems
      mediated by neurotransmitters, neuropeptides, hormones and cytokines, which form
      an integrated network to maintain normal physiological functions of the body. An
      imbalance in the NIM network is believed to accelerate the aging process, in
      which the thymus plays an important role. We recently discovered that thymectomy
      in mice not only reduces the immune response, but also deteriorates learning
      performances. Cytokines such as interleukin-1, interleukin-6 and tumor necrosis
      factor, and corticosterone affect the induction of hippocampal long-term
      potentiation, a synaptic model of memory. Clinical studies have demonstrated that
      Alzheimer's patients show disordered immune function in addition to cognitive
      deficit, and the brain lesions of Alzheimer's patients may be associated with
      abnormal immune reactions occurring in the brain. With these findings, it is
      speculated that the disordered immune function may induce an imbalance in the NIM
      network, which consequently influences central cognitive function.

PMID- 11292252
TI  - Phenotypic and functional characterization of human thymic stromal cell lines.
AB  - To establish new tools for studying human thymic stromal cells, we transfected
      adherent cells from a human postnatal thymus using a plasmid encoding SV40 large
      T antigen. Among the cell lines obtained, we characterized four epithelial cell
      lines (LT-TEC1 to LT-TEC4) and one thymic myoid cell line (MITC). Several
      morphological, functional and phenotypic differences were observed between these
      2 cell types. Epithelial cells were heterogeneous and larger than myoid cells.
      Untreated LT-TEC lines expressed MHC class I, ICAM-1 and LFA-3 antigens and not
      MHC class II antigens, similarly to primary thymic epithelial cells (PTEC), while
      MITC line expressed only class I and LFA-3 antigens. After IFN-gamma treatment,
      MHC class II and ICAM-1 antigens were markedly upregulated in LT-TEC lines but
      not in MITC, indicating the absence or a dysfunction of regulatory factors in
      MITC line. Myoid cells expressed mRNA for all the subunits of the acetylcholine
      receptor (AChR) while epithelial cells expressed only the alpha, beta and epsilon
      subunits. Strikingly, LT-TEC produced much more C-C chemokines and IL-6 than MITC
      cells, while these latter produced higher levels of IL-8 and TNF-alpha.
      Altogether, these results reveal phenotypic and functional differences between
      these two stromal cell types, suggesting a potential involvement of myoid cells
      in the thymic function.

PMID- 11292253
TI  - Thymic T-cell tolerance of neuroendocrine functions: physiology and
      pathophysiology.
AB  - Intimate interactions between the two major systems of cell-to-cell
      communication, the neuroendocrine and immune systems, play a pivotal role in
      homeostasis and developmental biology. During phylogeny as well as during
      ontogeny, the molecular foundations of the neuroendocrine system emerge before
      the generation of diversity within the system of immune defenses. Before reacting
      against non-self infectious agents, the immune system has to be educated in order
      to tolerate the host molecular structure (self). The induction of self-tolerance
      is a multistep process that begins in the thymus during fetal ontogeny (central
      tolerance) and also involves anergizing mechanisms outside the thymus (peripheral
      tolerance). The thymus is the primary lymphoid organ implicated in the
      development of competent and self-tolerant T-cells. During ontogeny, T-cell
      progenitors originating from hemopoietic tissues (yolk sac, fetal liver, then
      bone marrow) enter the thymus and undergo a program of proliferation, T-cell
      receptor (TCR) gene rearrangement, maturation and selection. Intrathymic T-cell
      maturation proceeds through discrete stages that can be traced by analysis of
      their cluster differentiation (CD) surface antigens. It is well established that
      close interactions between thymocytes (pre-T-cells) and the thymic cellular
      environment are crucial both for T-cell development and for induction of central
      self-tolerance. Particular interest has focused on the ability of thymic stromal
      cells to synthesize polypeptides belonging to various neuroendocrine families.
      The thymic repertoire of neuroendocrine-related precursors recapitulates at the
      molecular level the dual role of the thymus in T-cell negative and positive
      selection. Thymic precursors not only constitute a source of growth factors for
      cryptocrine signaling between thymic stromal cells and pre-T-cells, but are also
      processed in a way that leads to the presentation of self-antigens by (or in
      association with) thymic major histocompatibility complex (MHC) proteins. Thymic
      neuroendocrine self-antigens usually correspond to peptide sequences highly
      conserved during the evolution of their corresponding family. The thymic
      presentation of some neuroendocrine self-antigens does not seem to be restricted
      by MHC alleles. Through the presentation of neuroendocrine self-antigens by
      thymic MHC proteins, the T-cell system might be educated to tolerate main hormone
      families. More and more recent experiments support the concept that a defect in
      thymic tolerogenic function is implicated as an important factor in the
      pathophysiology of autoimmunity.

PMID- 11292254
TI  - Beta-adrenoceptor blockade alters thymocyte differentiation in aged mice.
AB  - The thymus is the primary site for generation of naive T-lymphocytes in the young
      animal. With age, the thymus progressively involutes and fewer mature T-cells are
      produced and migrate to the periphery. With thymic involution, increased density
      of sympathetic noradrenergic (NA) innervation and concentration of norepinephrine
      (NE) have been observed. To determine if the age-related changes in thymocyte
      differentiation are modified by NE signaling through beta-adrenergic receptors, 2
      month (mo) and 18-mo old BALB/c mice were implanted subcutaneously with pellets
      containing the non-selective beta-adrenoceptor antagonist nadolol. Four and one
      half weeks later, thymus and peripheral blood were collected to assess changes in
      thymocyte differentiation and naive T-cell output by flow cytometric analysis of
      T-cell subpopulations. In old mice, but not in young mice, thymocyte CD4/CD8 co
      expression was altered by beta-adrenoceptor blockade. In nadolol-treated old
      mice, the frequency of the immature CD4-8- population was increased, and the
      intermediate CD4+8+ population was reduced. A corresponding increase in the
      frequency of mature CD4-8+, but not CD4+8- cells was observed. The increase in
      CD4-8+ cells is most likely not mediated by more CD4-8+ cells undergoing positive
      selection, because CD3hi expression in the CD4+8+ population was not altered by
      nadolol. The percentage of CD8+44low naive cells in peripheral blood increased in
      nadolol-treated mice, suggesting that more CD4-8+ cells were exported from the
      thymus to the periphery. These results indicate that the age-associated increase
      in sympathetic NA innervation of the thymus modulates thymocyte maturation.
      Pharmacological manipulation of NA innervation may provide a novel means of
      increasing naive T-cell output and improving T-cell reactivity to novel antigens
      with age.

PMID- 11292255
TI  - Characterization of P2 receptors in thymic epithelial cells.
AB  - The presence of P2 receptors was investigated in three distinct preparations of
      murine thymic epithelial cells (TEC): 2BH4 murine cell line, IT45-R1 rat cell
      line, and a primary murine cell derived from the Nurse cell lympho-epithelial
      complex. In all preparations, application of ATP to the extracellular milieu
      triggered intracellular calcium signals indicating the presence of P2 receptor(s)
      in these cells. After an initial peak of calcium concentration, a plateau phase
      that could last more than 10 min was frequently observed. Ion replacement and
      channel blockage experiments indicated that the initial peak was associated with
      the release of calcium from intracellular stores, while the plateau phase was
      associated with an influx from the extracellular medium. ATP and UTP induced
      similar calcium signals, suggesting the presence of P2Y2 receptors in all three
      cell types. The murine 2BH4 cells also expressed P2X7/P2Z receptor, since under
      exposure to millimolar concentrations of ATP, a continuous rise in intracellular
      calcium concentration was observed and their plasma membranes became
      permeabilized to the fluorescent dyes Lucifer yellow and ethidium bromide. In
      addition, this permeabilization phenomenon was blocked by the P2Z-specific
      antagonist, oxidized ATP. RT-PCR assays confirmed the presence of mRNAs for the
      P2Y2 molecule in all TEC, while mRNA for the P2X7 molecule was detected only in
      2BH4 cells. Our data indicate that P2Y2 purinergic receptors are widely expressed
      by thymic epithelial cells, whereas the expression of the P2X7 receptor appears
      to be more restricted, raising the possibility that its expression is related
      only to a particular epithelial microenvironment within/the thymus.

PMID- 11292256
TI  - Signal transduction in thymus development.
AB  - Reciprocal interaction between bone marrow derived lymphoid precursor cells and
      the thymic environment leads, through a series of developmental events, to the
      generation of a diverse repertoire of functional T-cells. During thymopoiesis
      fetal liver or bone marrow derived precursors enter the thymus and develop into
      mature T-cells in response to cues derived from the environment. The thymic micro
      environment provides signals to the lymphoid cells as a result of cell-cell
      interactions, locally produced cytokines, chemokines and hormones. Developing
      thymocytes, in turn, influence the thymic stroma to form a supportive micro
      environment. Stage-specific signals provide an exquisite balance between cellular
      proliferation, differentiation, cell survival and death. The result of this
      intricate signaling concert is the production of the requisite numbers of well
      educated self-restricted T-cells. Mature T-cells are exported to the peripheral
      lymphoid organs, where, upon encountering antigen, naive T-cells further mature
      into effector cells that provide cytolytic or T helper functions. While there are
      extra-thymic locations for T-cell development, majority of T-cells in peripheral
      lymphoid organs are thymus derived. In mice and humans, T-cells develop
      throughout life although the efficacy declines significantly with age. It is not
      clear if this is a direct consequence of deterioration of the thymic environment
      by involution, a paucity of bone marrow derived precursors, or both. However, new
      data clearly shows that the involuted adult thymus retains the ability to
      generate new T-cells. Recent advances have revealed many components of an
      exquisitely balanced signaling cascades that regulate cell fate, cellular
      proliferation and cell death in the thymus. This article describes fundamental
      features of developing thymocytes and the thymic micro-environment as they relate
      to the signaling pathways.

PMID- 11292257
TI  - Maturation and function of mouse T-cells with a transgenic TCR positively
      selected by highly disparate xenogeneic porcine MHC.
AB  - Remarkably normal cellular immune function, along with specific T-cell tolerance
      to highly disparate xenogeneic donors, can be achieved by grafting fetal pig
      thymus (FP THY) tissue to T and NK cell-depleted, thymectomized (ATX) mice.
      Porcine MHC can mediate positive selection of mouse CD4+ T-cells with a mouse MHC
      restricted TCR in FP THY-grafted, T- and NK cell-depleted, ATX TCR-transgenic
      "AND" mice. However, functional studies were not performed on transgenic mouse T
      cells selected in a FP THY graft. We have now performed further studies to
      confirm the ability of porcine MHC to mediate the positive selection of mouse T
      cells with a mouse MHC-restricted TCR, and to exclude the possibility that the
      maturation of mouse T-cells with a mouse MHC-restricted TCR in FP THY grafts in
      ATX "AND" mice is a special case. For this purpose, TCR-transgenic mice with an
      unrelated transgenic TCR ["3A9", specific for hen egg lysozyme (HEL) peptide 46
      61 presented by I-Ak] were employed. Similar to FP THY-grafted ATX "AND" mice,
      large numbers of mouse CD4 single positive thymocytes expressing the transgenic
      TCR (Vbeta8.2) and expressing a mature phenotype (Qa-2high and heat stable
      antigen, HSAlow) were detected in FP THY grafts. Porcine thymus grafting led to a
      high level of peripheral repopulation with mouse naive-type (CD44low CD45RBhigh
      CD62Lhigh) CD4+ cells expressing the transgenic TCR in T and NK cell-depleted ATX
      "3A9" mice, regardless of whether the recipients had a positive selecting or a
      non-selecting, class II deficient MHC background. The mouse CD4+ T-cells
      expressing the "3A9" TCR showed efficient primary proliferative responses to the
      protein antigen (HEL) when it was presented by mouse class II+ antigen presenting
      cells (APC) in vitro. These results, collectively, support the general conclusion
      that discordant xenogeneic porcine MHC can mediate positive selection of mouse T
      cells with mouse MHC-restricted TCR. This study has implications for the
      potential clinical use of xenogeneic thymus transplantation to reconstitute
      cellular immunity in the setting of thymic insufficiency or thymectomy, and hence
      for its applicability to the induction of xenograft tolerance and in the
      treatment of immunodeficiency diseases.

PMID- 11292258
TI  - Biochemical and functional characterization of a molecule expressed by a subset
      of thymic medullary epithelial cells.
AB  - A monoclonal antibody (mAb), named TE-4F 10, was produced by fusing P3X-Ag8
      myeloma cells with splenocytes of BALB/c mice immunized with a rat medullary
      thymic epithelial cell (TEC) line, (TE-R 2.5), previously established in our
      Institute. Flow cytometry showed that 85-95% TE-R 2.5 cells expressed the TE-4F10
      antigen. The mAb immunoprecipitated a 29 kDa molecule from the TE-R2.5 cell
      lysate. Immunohistochemical analysis using single and double staining of the
      thymus with anti-cytokeratin (CK) mAb, showed that TE- 4F10 mAb selectively
      stains a subpopulation of medullary TEC. Hematopoietic and lymphoid cells were
      negative. The expression of the TE-4F10 antigen on TE-R 2.5 cells in vitro was
      significantly upregulated by interleukin 1 (IL-1) and tumor necrosis factor
      (TNFalpha). Other cytokines IL-4, IL-6, IL-10 and granulocyte - macrophage colony
      stimulating factor (GM-CSF) showed lesser stimulation on its expression, whereas
      interferon gamma (IFN) and dexamethasone were without significant effect. The TE
      R 2.5 cell line strongly bound and induced apoptosis of a rat / mouse thymocyte
      heterohybridoma (BWRT8), phenotypically alphabetaTCRhiCD4hiCD8lo. TE-4F10 mAb
      significantly inhibited binding (40-50%) of both BWRT8 cells and the BWRT8 -
      MDP.1 subclone to TE-R 2.5 cells. The inhibition was enhanced when TEC were
      stimulated with IL-1 + TNFalpha. The mAb also significantly blocked apoptosis of
      BWRT8 but did not modulate cell death of the BWRT8 - MDP.1 subclone, which was
      resistant to TEC-induced apoptosis. These findings indicate that the TE-4F10
      antigen might be selectively involved in adhesion and selection processes in the
      medullary thymic microenvironment. The mAb of the same characteristics has not
      been described so far.

PMID- 11292259
TI  - Development of dendritic cells in culture from human and murine thymic precursor
      cells.
AB  - The earliest T-precursor population in the adult murine thymus can give rise to
      dendritic cells (DC) in culture if stimulated with a cocktail of cytokines that
      includes interleukin (IL)-3, but not with cytokine mixes based on granulocyte
      macrophage colony stimulating factor (GM-CSF), normally used to generate myeloid
      derived DC. This and other evidence led to the proposal that two different
      lineages of DC exist, one lymphoid-related and the other myeloid-related. To
      determine whether this selective response to cytokines was restricted to murine
      DC, early human thymic T-precursors were isolated and their capacity to generate
      DC in response to various cytokines directly compared to their murine
      counterparts. In contrast to cultures of murine thymic precursors, CD34+CD1a-
      lineage marker negative (Lin-) precursor cells from the human thymus proliferated
      and generated DC with both the IL-3-containing cytokine mix lacking GM-CSF and
      with GM-CSF based cytokine mixes. These CD34+CD1a-Lin- human precursor cells also
      gave rise to NK cells under appropriate culture conditions, but produced no
      granulocyte, monocyte, eosinophil, megakaryocyte or erythroid cells in standard
      soft-agar colony-forming cell assays. Thus, although apparently lymphoid
      restricted, the human thymic DC precursors responded to the myeloid factor GM-CSF
      as well as to the cytokines selective for murine lymphoid-related DC.

PMID- 11292260
TI  - Presence and possible functional role of nerve growth factor in the thymus.
AB  - We have previously reported that the nerve growth factor (NGF), a polypeptide
      known for its neurotrophic activities, is also involved in proliferation, growth
      and survival of cells of the immune system. Working with animal models, we found
      that NGF and NGF-receptors (NGF-r) are present in the cells of the medullary
      layer of the thymus, a lymphoid gland involved in the production and
      differentiation of T-lymphocytes. Using immunohistochemical and biochemical
      approaches, we also showed that the expression of NGF in the thymus is high
      during late prenatal life and decreases later in postnatal life. A significant
      alteration of NGF levels was also found during pregnancy and aging, two events
      characterized by thymic involution. The aim of this study is to investigate
      whether NGF and NGF-r expression in the thymus are influenced by immuno- and
      neuro-pathological events. These observations will be presented and discussed.

PMID- 11292261
TI  - Fetal thymi from diabetes-prone but not diabetes-resistant BB/Wor rats fail to
      generate mature ART2+ T-cells in organ culture.
AB  - Diabetes-prone (BBDP) BB rats develop spontaneous autoimmune diabetes mellitus.
      They are lymphopenic and severely deficient in ART2+ T-cells. Diabetes-resistant
      BB (BBDR) rats do not develop spontaneous diabetes and have normal numbers of
      ART2+ T-cells. T-cell lymphopenia in BBDP rats results from hematopoietic stem
      cell defects leading to abnormal intrathymic T-cell maturation. To study this
      process, we established rat fetal thymic organ cultures (FTOC). Like mouse FTOC,
      cultures of BBDR rat thymi yielded approximately 10(5) cells per lobe. The
      majority of cells were CD8+ART2+ T-cells. In contrast, BBDP rat FTOC yielded 60%
      fewer cells (approximately 0.3 x 10(5)/lobe), a smaller percentage of CD8+ and
      TcRalphabeta+ T-cells, and almost no detectable ART2+ T-cells. ART2 mRNA was
      detectable in BBDR but not BBDP FTOC. In contrast, expression of mRNAs encoding
      bcl-2 and a panel of cytokines was comparable in BBDP and BBDR FTOC. Addition of
      anti-ICAM-1 (CD54) antibody reduced T-cell number in BBDR rat FTOC by
      approximately 70%, but addition of IL-7 or IL-1beta had no effect. The data
      demonstrate that BBDP thymocytes fail to generate mature ART2+ T-cells in rat
      FTOC, a system that can now be used to study the mechanism of this process.

PMID- 11292262
TI  - The "early' CD4+CD8+ stage of thymocte differentiation hallmarks the end of a
      strong positive correlation between extracellular matrix receptor expression and
      protein tyrosine phosphorylation.
AB  - We used irradiation-induced thymic regression/reconstitution to study
      phosphotyrosine (PTyr) levels and expression of extracellular matrix receptors in
      thymocyte subsets by flow cytometry. High PTyr levels (PTyr(hi)) characterized
      cells from the CD4-CD8-(DN)CD25in/hi to the "early" CD4-CD8+(DP)CD25- stage.
      Correlation indexes (R) between the percentages of these PTyrhi cells and cells
      with up-regulated expression of alpha4 integrin (alpha4hi) were strongly positive
      (R= 0.91, P= 0.002, for DN; R= 0.98, P= 0.0001 for DP). At the "early" DP stage,
      R between PTyrhi cells and cells with up-regulated expression of alpha5 integrin
      and L-selectin (alpha5hi and L-sel(hi)) also rendered strongly positive (R>0.95,
      p<0.0003). "Late" expanding DP cells exhibited intermediate PTyr levels
      (PTyr(in)), associated with a down-regulation of the adhesion receptors assessed.
      Triple-labeling suggested that in most early CD3-/lo cells, alpha4hi and
      alpha5hi, but not L-sel(hi) expression preceded a PTyr(hi) content. CD3in/hi
      enriched CD8+ cells were also PTyr(hi), but conversely to the immature ones
      exhibited a tendency for a negative R between PTyr(hi) and alpha4hi (R = -0.93, P
      = 0.067, n= 4) or alpha5hi cells (R = -0.77, P = 0.23, n = 4). CD4+ cells were
      either PTyr(hi) or PTyr(in), exhibiting a tendency for a positive R (R = 0.59, P
      = 0.124, n= 8) between PTyr(hi) and L-sel(hi) cells only. In conclusion, our
      results associate an up-regulation of alpha4 and alpha5 chains expression with
      PTyr(hi) levels and, as elsewhere published, with increased adhesion to
      fibronectin up to the "early" DP stage, but not afterwards.

PMID- 11292263
TI  - Post-thymic selection of peripheral CD4+ T-lymphocytes on class II major
      histocompatibility antigen-bearing cells.
AB  - Following positive and negative selection in the thymus, mature CD4+ T-cells
      emigrate into peripheral lymphoid organs. Whether resting T-cells require
      periodic stimulation to remain viable in the absence of antigen is important for
      understanding peripheral T-cell homeostasis. A prerequisite for T-cell receptor
      (TCR)-mediated signals in maintaining peripheral CD4+ T-cell longevity has been
      demonstrated. Here, we show in mice expressing a mutant I-Abeta transgene on an I
      Abeta knockout background that naive CD4+ T-cells also require engagement of
      their CD4 coreceptors by peripheral, class II MHC-bearing cells for their
      survival. The transgene's product combines with endogenous Aalpha, but this
      mutant AalphaAbeta heterodimer cannot interact with CD4 molecules, although it
      efficiently presents antigens to TCRs. Resting CD4+ T-lymphocytes from mutant
      Abeta transgenic mice die by apoptosis at a much higher rate than do CD4+ T-cells
      from normal mice. Apoptosis of CD4+ T-cells in mutant Abeta transgenic mice is
      partially mediated by Fas. Adoptive transfer experiments revealed that the
      increase in apoptosis is due to a lack of interactions with mutant MHC class II
      rather than to an intrinsic defect in the CD4+ T-cells selected on mutant Abeta
      expressing thymic epithelial cells. Thus, interactions between CD4 and MHC class
      II molecules contribute to the regulation of homeostasis in the peripheral immune
      system. Our results further suggest that thymic emigrant cells are continuously
      retested in the periphery for appropriate coreceptor interactions. Peripheral
      selection may be important in eliminating potentially autoreactive T-cells.

PMID- 11292264
TI  - Hypothalamic control of thymic function.
AB  - Removal of the pituitary gland results in atrophy of the thymus. As the former is
      under the control of hypothalamus, destruction of anterior portion of the
      hypothalamus (AHTL) would be expected to negatively influence the thymic
      function. Contrary to our expectation, however, the thymus became hypertrophic
      and serum level of growth hormone (GH) markedly increased, when the anterior
      portion of the hypothalamus was destroyed in rats at 1 month of age and older.
      The results suggested that AHTL removed the cells secreting GHRIH (growth hormone
      release inhibitory hormone), but not GHRH (growth hormone releasing hormone),
      leading to increased pituitary secretion of GH. This high serum level of GH
      appeared to be responsible for the thymic hyperplasia occurring after AHTL. In
      other words, the development and aging of the thymus appear to be dependent on
      the serum level of GH which is under the balance of positive (GHRH) and negative
      (GHRIH) signals from the hypothalamus. In rats and mice, the serum level of GH is
      very high just after birth, quickly declines in young adults and does not change
      greatly thereafter. Thus, it is likely that the initial positive signal is high
      just after birth and decreasing thereafter with a concomitant increase of
      negative signal, leading to the onset ofthymic atrophy at around puberty, in
      association with sex steroid release.

PMID- 11292265
TI  - Comorbidity studies: a core area for psychosomatic research.

PMID- 11292266
TI  - History of treatment for depression: risk factor for myocardial infarction in
      hypertensive patients.
AB  - OBJECTIVE: Psychological factors have been suspected of contributing to the
      development of cardiovascular disease. This study examined the relationship
      between a self-reported history of treatment for depression and subsequent
      myocardial infarction among treated hypertensive patients. METHODS: Participants
      (5564) in a union-sponsored, hypertension control program in New York City, who
      entered the program during 1981-1994 without a history of cardiovascular disease
      and who were asked whether they had been treated for depression, were followed in
      a prospective cohort study. The primary outcome of interest was hospitalization
      or death due to myocardial infarction. RESULTS: At entry, 3.5% of men and 6.4% of
      women reported a history of treatment for depression. During 4.9 years (average)
      of follow-up, 112 fatal and nonfatal myocardial infarctions were recorded. The
      sex-adjusted relative risk of myocardial infarction was 2.24 (confidence interval
      = 1.13-4.45). Controlling for known cardiovascular risk factors with multivariate
      proportional hazards models, history of treatment for depression was
      significantly associated with subsequent myocardial infarction (hazard ratio =
      2.10, confidence interval = 1.04-4.23). CONCLUSIONS: A self-reported history of
      treatment for depression is independently associated with subsequent myocardial
      infarction in treated hypertensive patients without prior cardiovascular disease.
      Whether additional or different treatment for depression will be cardioprotective
      is unknown and merits further study.

PMID- 11292267
TI  - The association between emotional well-being and the incidence of stroke in older
      adults.
AB  - OBJECTIVE: Individuals with high levels of depressive symptoms have an increased
      risk of many illnesses, including stroke. Measures of depressive symptoms include
      questions about the presence of negative affect, such as sadness, as well as the
      absence of positive affect, such as happiness and optimism. We assessed whether
      positive or negative affect, or both, predicted risk of stroke. METHODS: Data
      were from a 6-year prospective cohort study of a population-based sample of 2478
      older whites and blacks from five counties in North Carolina who reported no
      history of stroke at the baseline interview. Baseline, in-person interviews were
      conducted to gather information on sociodemographic, psychosocial, and health
      related characteristics of subjects. Thereafter interviews were conducted
      annually for 6 years. RESULTS: Increasing scores on the modified version of the
      Center for Epidemiological Studies Depression Scale (CES-D) were significantly
      associated with stroke incidence for the overall sample (relative risk [RR] =
      1.04 for each one-point increase, 95% confidence interval [CI] = 1.01-1.09) over
      the 6-year follow-up period after adjusting for sociodemographic characteristics,
      blood pressure, body mass index, smoking status, and selected chronic diseases.
      Positive affect score demonstrated a strong inverse association with stroke
      incidence (RR = 0.74, 95% CI = 0.62-0.88). CONCLUSIONS: Increasing scores on the
      modified CES-D are related to an increased risk of stroke, whereas high levels of
      positive affect seem to protect against stroke in older adults.

PMID- 11292268
TI  - Psychological factors and delayed healing in chronic wounds.
AB  - OBJECTIVE: Studies have shown that stress can delay the healing of experimental
      punch biopsy wounds. This study examined the relationship between the healing of
      natural wounds and anxiety and depression. METHODS: Fifty-three subjects (31
      women and 22 men) were studied. Wound healing was rated using a five-point Likert
      scale. Anxiety and depression were measured using the Hospital Anxiety and
      Depression Scale (HAD), a well-validated psychometric questionnaire.
      Psychological and clinical wound assessments were each conducted with raters and
      subjects blinded to the results of the other assessment. RESULTS: Delayed healing
      was associated with a higher mean HAD score (p = .0348). Higher HAD anxiety and
      depression scores (indicating "caseness") were also associated with delayed
      healing (p = .0476 and p = .0311, respectively). Patients scoring in the top 50%
      of total HAD scores were four times more likely to have delayed healing than
      those scoring in the bottom 50% (confidence interval = 1.06-15.08). CONCLUSIONS:
      The relationship between healing of chronic wounds and anxiety and depression as
      measured by the HAD was statistically significant. Further research in the form
      of a longitudinal study and/or an interventional study is proposed.

PMID- 11292269
TI  - Mortality and quality of life 12 months after myocardial infarction: effects of
      depression and anxiety.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of symptoms of
      depression and anxiety on mortality and quality of life in patients hospitalized
      for acute myocardial infarction (MI). METHODS: The Beck Depression Inventory and
      the State-Trait Anxiety Inventory were completed by 288 patients hospitalized for
      MI. Twelve-month survival status was ascertained, and quality of life among
      survivors was assessed at 12 months using the Dartmouth COOP charts. RESULTS:
      Thirty-one (10.8%) patients died, 27 of cardiac causes, during the 12-month
      follow-up. Symptoms of depression and anxiety predicted neither cardiac nor all
      cause mortality. Severity of infarction and evidence of heart failure predicted
      both cardiac and all-cause mortality. The same findings emerged from
      supplementary analyses of data from patients who died after discharge from the
      hospital. Symptoms of depression and anxiety, measured at entry, predicted 12
      month quality of life among survivors, as did gender, partner status, employment
      status, living alone, previous frequency of exercise, and indices of disease
      severity (Killip class and Peel Index). In a multiple regression model in which
      all of these variables were entered, initial depression scores provided the best
      independent prediction of quality of life, although living alone, severity of
      infarction, and state anxiety also entered the model. CONCLUSIONS: Symptoms of
      depression and anxiety did not predict either cardiac or all-cause mortality
      after MI, but they did predict quality of life among those who lived to 12
      months.

PMID- 11292270
TI  - Classic conditioning and dysfunctional cognitions in patients with panic disorder
      and agoraphobia treated with an implantable cardioverter/defibrillator.
AB  - OBJECTIVE: A model for the development of anxiety disorders (panic disorder with
      or without agoraphobia) is needed. Patients with an implantable
      cardioverter/defibrillator (ICD) are exposed to repeated electric shocks. If the
      theory of anxiety development by aversive classic conditioning processes is
      valid, these repeated shocks should lead to an increased risk of anxiety
      disorders. To study this hypothesis, we retrospectively studied 72 patients after
      implantation of an automatic ICD. METHODS: Patients were assessed with the
      semistructured Diagnostic Interview of Psychiatric Disease 1 to 6 years after
      implantation of an automatic ICD. Panic disorder and/or agoraphobia was diagnosed
      in patients who fulfilled all DSM-III-R criteria for those conditions. RESULTS:
      Anxiety disorder developed in 15.9% of patients after ICD implantation. This was
      significantly related to the frequency of repeated defibrillation (shocks) to
      stop malignant ventricular arrhythmias. Dysfunctional cognitions are an
      additional vulnerability factor. CONCLUSIONS: The data support both the
      conditioning hypothesis and the cognitive model of anxiety development. These
      findings suggest that ICD patients are an appropriate risk population for a
      prospective study of the development of anxiety disorders.

PMID- 11292271
TI  - The distribution of psychiatric and somatic III health: associations with
      personality and socioeconomic status.
AB  - OBJECTIVE: Psychiatric and somatic disorders frequently co-occur in the same
      individuals. We examined whether this happens because these types of morbidity
      share risk factors or because they are risk factors for each other. METHODS:
      Negative binomial regression was used to examine, in a random sample of Dutch
      adults (N = 7076), cross-sectional associations of sociodemographic and
      personality variables like income and neuroticism with the presence, over 1 year,
      of 30 somatic and 13 psychiatric disorders, with the latter diagnosed by
      structured interview. We examined to what extent the links of these variables
      with these two morbidity types were independent of each other. RESULTS: This
      population experienced 5050 somatic and 2438 psychiatric disorders during the
      preceding year. Subjects reporting more somatic disorders had more psychiatric
      disorders. Neuroticism, followed closely by low educational attainment, was the
      strongest correlate of both morbidity types. After adjustment for all other
      covariates including somatic morbidity, the number of psychiatric diagnoses rose
      1.84-fold (95% confidence interval = 1.74-1.94) per standard deviation increase
      in neuroticism. Likewise, adjusted for all other covariates including psychiatric
      diagnoses, 1.42 (95% confidence interval = 1.35-1.50) times more somatic
      disorders were reported per standard deviation increase in neuroticism.
      CONCLUSIONS: Personal features like neuroticism and low educational attainment
      are linked with psychiatric and with somatic morbidity. These links are largely
      independent. Although this study was cross-sectional, the results suggest that
      these different types of morbidity may have overlapping etiologies. Key words:
      Comorbidity, multimorbidity coefficient, negative binomial regression,
      epidemiology, neuroticism, social class.

PMID- 11292272
TI  - Depression and self-reported physical health in patients with coronary disease:
      mediating and moderating factors.
AB  - OBJECTIVES: The purpose of this study was to define how the relation between
      depression and self-reported physical health in patients with coronary disease is
      modified by other patient-centered factors. METHODS: We conducted a prospective
      cohort study of 111 patients (members of a health maintenance organization) with
      angiographically documented coronary disease, examining factors (physical
      symptoms, psychological states and traits, and spousal support) modifying the
      relation between depression and patient-reported physical health 5 years later
      using multiple hierarchical regression models. RESULTS: Five regression models
      (all including demographic and disease severity covariates) were constructed to
      predict physical health from depression only (R2 = 0.22); depression plus angina
      and fatigue (R2 = 0.53); depression plus positive affect and novelty seeking and
      their interaction (R2 = 0.48); depression plus spousal support (R2 = 0.27); and
      depression, angina, fatigue, positive affect, and novelty seeking (overall model)
      (R2 = 0.65). Depression remained significant in each model, but the proportion of
      variance it predicted was diminished in the presence of the other variables
      (bivariate r = 0.39, partial r = 0.37-0.13). CONCLUSIONS: The effect of
      depression on self-reported physical health is significantly mediated by physical
      symptoms (angina and fatigue), personality states and traits (positive affect and
      novelty seeking), and spousal support. Positive affect and novelty seeking had
      more marked effects on physical health in the presence of more depression. Thus,
      a broad range of factors beyond the severity of coronary disease itself affect
      the perceived physical health of patients with coronary heart disease.

PMID- 11292273
TI  - Clinical implications of a reduction in psychological distress on cardiac
      prognosis in patients participating in a psychosocial intervention program.
AB  - OBJECTIVE: The objective of this secondary analysis was to examine the
      relationships between a reduction in psychological distress and long-term cardiac
      and psychological outcomes in post-myocardial infarction patients who
      participated in a randomized trial of home-based psychosocial nursing
      interventions (the Montreal Heart Attack Readjustment Trial [M-HART]). Gender
      differences were considered. METHODS: We studied 433 patients (36.0% women) from
      the M-HART treatment group who received two home visits after achieving a high
      psychological distress score (ie, > or =5) on the General Health Questionnaire
      (GHQ). Short-term GHQ success was determined by a return to a normal GHQ score
      (<5) or a reduction of > or =50% after the two visits. Patients with short-term
      successful and unsuccessful GHQ outcomes were compared for mid-term maintenance
      of success, 1-year death and readmission rates, and 1-year depression and anxiety
      symptoms. RESULTS: Patients with short-term GHQ success were more likely to show
      mid-term GHQ success (p < .001), marginally less likely to die of any causes (p =
      .087), less likely to die of cardiac causes (p = .043), less likely to be
      readmitted for any reason (p < .001) and for cardiac reasons (p < .001), and less
      likely to have high depression (p < .001) and anxiety (p < .001) at 1-year than
      patients with short-term unsuccessful GHQ outcomes. Results held for men and
      women and were not altered by controlling for potential confounders. However, the
      number of deaths prevented analysis with statistical controls. CONCLUSIONS: Post
      myocardial infarction interventions that reduce psychological distress have the
      potential to improve long-term prognosis and psychological status for both men
      and women.

PMID- 11292274
TI  - Characteristics of socially isolated patients with coronary artery disease who
      are at elevated risk for mortality.
AB  - OBJECTIVES: Social isolation has been linked to poor survival in patients with
      coronary artery disease (CAD). Few studies have closely examined the psychosocial
      characteristics of CAD patients who lack social contact. METHODS: Social
      isolation was examined as a predictor of mortality in 430 patients with
      significant CAD. More isolated patients were compared with their less isolated
      counterparts on factors that might help explain the association between isolation
      and survival. RESULTS: The mortality rate was higher among isolated individuals.
      Those with three or fewer people in their social support network had a relative
      risk of 2.43 (p = .001) for cardiac mortality and 2.11 (p = .001) for all-cause
      mortality, controlling for age and disease severity. Adjustments for income,
      hostility, and smoking status did not alter the risk due to social isolation.
      With the exception of lower income, higher hostility ratings, and higher smoking
      rates, isolated patients did not differ from nonisolated patients on demographic
      indicators, disease severity, physical functioning, or psychological distress.
      Isolated patients reported less social support and were less pleased with the way
      they got along with network members, but they did not report less satisfaction
      with the amount of social contact received. CONCLUSIONS: Patients with small
      social networks had an elevated risk of mortality, but this greater risk was not
      attributable to confounding with disease severity, demographics, or psychological
      distress. These findings have implications for mechanisms linking social
      isolation to mortality and for the application of psychosocial interventions.

PMID- 11292275
TI  - Social isolation kills, but how and why?

PMID- 11292276
TI  - Prepulses reduce the pain of cutaneous electrical shocks.
AB  - OBJECTIVE: Both the startle reflex elicited by an intense acoustic or tactile
      stimulus and the perceived intensity of that stimulus can be diminished by a weak
      "prepulse" that precedes the startling stimulus. The present study examined
      whether prepulses can also diminish the pain produced by an intense electrical
      stimulus similar to that used to treat life-threatening cardiac arrhythmias in
      conscious patients with implantable cardioverter/defibrillators or transcutaneous
      pacemakers. METHODS: Perceptual and pain thresholds for electrical shocks to the
      arm were determined in 20 adults. Participants then rated the painfulness of 25
      electrical shocks that were 1.5 times the pain threshold (mean shock intensity,
      approximately 160 V) and either presented alone or preceded (at 40-60 ms) by weak
      electrical prepulses equal to or 25% above the perceptual threshold. RESULTS:
      Prepulses significantly reduced the pain produced by the intense shocks.
      Individuals with the lowest pain thresholds experienced the greatest pain
      reduction with prepulses. In these more sensitive individuals, the most effective
      prepulses reduced perceived pain by 26% across the entire test session and by 54%
      in the initial block of five shocks. CONCLUSIONS: Prepulses may be useful in
      diminishing the pain associated with the therapeutic electrical shocks used to
      treat cardiac arrhythmias.

PMID- 11292277
TI  - Psychosocial variables are associated with atherosclerosis risk factors among
      women with chest pain: the WISE study.
AB  - OBJECTIVE: We investigated associations between atherosclerosis risk factors
      (smoking behavior, serum cholesterol, hypertension, body mass index, and
      functional capacity) and psychological characteristics with suspected linkages to
      coronary disease (depression, hostility, and anger expression) in an exclusively
      female cohort. METHODS: Six hundred eighty-eight middle-aged women with chest
      pain warranting clinical investigation completed a comprehensive diagnostic
      protocol that included quantitative coronary angiography to assess coronary
      artery disease (CAD). Primary analyses controlled for menopausal status, age, and
      socioeconomic status variables (income and education). RESULTS: High depression
      scores were associated with a nearly three-fold risk of smoking (odds ratio (OR)
      = 2.8, 95% confidence interval (CI) = 1.4-5.7) after covariate adjustment, and
      women reporting higher depression symptoms were approximately four times more
      likely to describe themselves in the lowest category of functional capacity (OR =
      3.7, 95% CI = 1.7-7.8). High anger-out scores were associated with a four-fold or
      greater risk of low high-density lipoprotein cholesterol concentration (<50
      mg/dl; OR = 4.0, 95% CI = 1.4-11.1) and high low-density lipoprotein cholesterol
      concentration (>160 mg/dl; OR = 4.8, 95% CI = 1.5-15.7) and a larger body mass
      index (OR = 3.5, 95% CI = 1.1-10.8) after covariate adjustment. CONCLUSIONS:
      These results demonstrate consistent and clinically relevant relationships
      between psychosocial factors and atherosclerosis risk factors among women and may
      aid our understanding of the increased mortality risk among women reporting high
      levels of psychological distress.

PMID- 11292278
TI  - Hemodynamic and emotional responses to a psychological stressor after cardiac
      transplantation.
AB  - OBJECTIVE: Because cardiac transplantation entails neuronal decentralization,
      cardiac responses to a psychological stressor in transplant patients would be
      expected to rely on circulating hormonal factors and therefore to be delayed and
      prolonged. We tested this prediction by comparing stress responses after
      transplantation with those in patients with coronary artery bypass grafts (to
      control for experience of surgery) or heart failure (to control for heart
      disease). METHODS: Fifty-six transplantation patients, 66 bypass patients, and 40
      patients with heart failure underwent a 10-minute, computer-generated, Stroop
      color-word conflict test. Heart rate and systolic and diastolic blood pressures
      were recorded continuously for 1 minute before, during, and 12 minutes after the
      stressor. Emotional state was measured periodically by questionnaires. RESULTS:
      All hemodynamic variables were increased by the Stroop test. There was a pattern
      of blunted response to the Stroop test after cardiac transplantation,
      particularly in comparison with bypass patients, and slower recovery in
      comparison with both control groups. Emotional stress responses were similar in
      each group. CONCLUSIONS: This pattern cannot be attributed to the experience of
      major heart surgery or to cardiac disease. Nor can it be explained by differences
      in central processing of stress. Correspondingly the changed hemodynamic response
      to the Stroop test after cardiac transplantation evidently does not affect
      patients' emotional responses. The hemodynamic findings are consistent with an
      increased reliance on hormonal rather than neuronal hemodynamic regulation after
      cardiac transplantation.

PMID- 11292279
TI  - Central nervous system serotonin function and cardiovascular responses to stress.
AB  - OBJECTIVE: The objective of this study was to evaluate the impact of indices of
      central nervous system (CNS) serotonin function on cardiovascular reactivity to
      mental stress. METHODS: Lumbar puncture was performed on 54 healthy volunteers to
      obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid
      (5HIAA) levels. Genotypes were determined with respect to a functional
      polymorphism of the serotonin transporter gene promoter region (5HTTLPR).
      Subjects then underwent mental stress testing. RESULTS: Persons with one or two
      long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA,
      that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons
      with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood
      pressure and heart rate responses to a mental stress protocol. CONCLUSIONS: These
      findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and
      they are consistent with the general hypothesis that CNS serotonin function is
      involved in the regulation of potentially health-damaging biobehavioral
      characteristics. In particular, the l allele could contribute, through its
      association with increased cardiovascular reactivity to stress, to increased risk
      of cardiovascular disease.

PMID- 11292280
TI  - Stressful life events and survival after breast cancer.
AB  - OBJECTIVE: This study assessed the relation of stressful life events with
      survival after breast cancer. METHODS: This study was based on women with
      histologically confirmed, newly diagnosed, localized or regional stage breast
      cancer first treated in 1 of 11 Quebec City (Canada) hospitals from 1982 through
      1984. Among 765 eligible patients, 673 (88%) were interviewed 3 to 6 months after
      diagnosis about the number and perceived impact of stressful events in the 5
      years before diagnosis. Three scores were calculated: number of events; number
      weighted by reported impact; and for almost 80% of events, number weighted by
      community-derived values reflecting adjustment required by the event. Scores were
      divided into quartiles to assess possible dose-response relationships. Survival
      was assessed in 1993. Hazard ratios and 95% confidence intervals (CIs) comparing
      all-cause and breast cancer-specific mortality were calculated with adjustment
      for age, presence of invaded axillary nodes, adjuvant radiotherapy, and systemic
      therapy (ie, chemotherapy and hormone therapy). RESULTS: When quartiles 2, 3, and
      4 were compared with the appropriate lowest quartile, adjusted hazard ratios for
      all-cause mortality were 0.99 (CI = 0.70-1.38), 0.97 (CI = 0.73-1.31), and 1.04
      (CI = 0.78-1.40) for number, number weighted by impact, and number weighted by
      community-derived values, respectively. Results were essentially similar for the
      relation between stressful life events limited to those occurring within the 12
      months before diagnosis and overall mortality and between stressful life events
      in the 5 years before diagnosis and breast cancer-specific mortality.
      CONCLUSIONS: Stress was conceptualized as life events presumed to be negative,
      undesirable, or to require adjustment by the person confronting them. We found no
      evidence indicating that this kind of stress during the 5 years before diagnosis
      negatively affected survival among women with nonmetastatic breast cancer.
      Evidence from this study and others on the lack of effect of this type of stress
      on survival may be reassuring for women living with breast cancer.

PMID- 11292281
TI  - Ethnic differences in pain tolerance: clinical implications in a chronic pain
      population.
AB  - OBJECTIVE: Although numerous studies have independently examined ethnic
      differences in clinical and experimental pain, few have investigated differences
      in both sensitivity to controlled noxious stimuli and clinical pain reports in
      the same sample. The present experiment examined the effects of ethnicity
      (African American vs. white) on experimental pain tolerance and adjustment to
      chronic pain. METHODS: Three hundred thirty-seven (68 African American and 269
      white) patients with chronic pain referred to a multidisciplinary treatment
      center participated in the study. In addition to completing a number of
      standardized questionnaires assessing adjustment to chronic pain, participants
      underwent a submaximal effort tourniquet procedure. This experimental pain
      procedure yields a measure of tolerance for a controlled noxious stimulus (ie,
      arm ischemia). RESULTS: African American subjects reported higher levels of
      clinical pain as well as greater pain-related disability than white participants.
      In addition, substantial group differences were observed for ischemic pain
      tolerance, with African Americans demonstrating less tolerance than whites.
      Correlational analyses revealed a small but significant inverse relationship
      between ischemic pain tolerance and the reported severity of chronic pain.
      CONCLUSIONS: Collectively these findings support previous research revealing
      ethnic differences in responses to both clinical and experimental pain. Moreover,
      the present results suggest that enhanced sensitivity to noxious stimuli on the
      part of African Americans may be associated with ethnic differences in reported
      clinical pain, although the magnitude of ethnic differences was much greater for
      ischemic pain tolerance than for clinical pain measures.

PMID- 11292282
TI  - No more "Slavery Hypothesis" yarns.

PMID- 11292283
TI  - Salt, hypertension, evolution.

PMID- 11292284
TI  - The new chimaera: the industrialization of organ transplantation. International
      Forum for Transplant Ethics.
AB  - Clinical organ transplantation has evolved through advances in patient care in
      parallel with investigations in associated biologies. It has developed from a
      cottage industry to an important medical specialty driven increasingly by the
      availability of newer and more effective immunosuppressive drugs, and dependent
      on consistently close collaborations between university-based clinical scientists
      and the pharmaceutical industry. Particularly during the past decade, however,
      this industry has undergone striking changes, consolidating into huge multi
      national corporations, each competing for patients, their doctors, and for
      support of the allied hospitals. Because of the growth of "Big Pharma," the
      relationship between academia and industry has changed. There have been many
      advantages to such mutually dependent interactions. A combination of university
      based expertise and the specialized knowledge and resources of industry have
      produced important scientific gains in drug development. Commercial sponsorship
      of applied research has been crucial. The orchestration of multicenter controlled
      clinical drug trials has provided invaluable information about the effectiveness
      of newer agents. But there are also disadvantages of increasing concern. Indeed,
      the power of "Big Pharma" in many medical fields including transplantation is
      such that presentation of data can be delayed, adverse results withheld, and
      individual investigations hampered. Clinical trials may be protracted to stifle
      competition. Monetary considerations may transcend common sense. Several measures
      to enhance the clinical relationship between the pharmaceutical industry and
      those involved with organ transplantation are suggested, particularly the use of
      third party advisors in the production of clinical trials, support for more basic
      research and in the dissemination of results. In this way, the increasingly
      problematic phenomenon of commercialization of the field of transplantation can
      be tempered and controlled.

PMID- 11292285
TI  - Accommodation and the reversibility of biological systems.

PMID- 11292286
TI  - Liver transplantation for mitochondrial respiratory chain disorders: to be or not
      to be?

PMID- 11292287
TI  - Nitric oxide-mediated expression of Bcl-2 and Bcl-xl and protection from tumor
      necrosis factor-alpha-mediated apoptosis in porcine endothelial cells after
      exposure to low concentrations of xenoreactive natural antibody.
AB  - BACKGROUND: Cardiac and renal allo- and xenografts can acquire a natural
      resistance to vascular rejection. This "accommodation" involves endothelial cell
      (EC) expression of "survival genes" such as Bcl family members and hemoxygenase
      1. Understanding what initiates this protective process would have profound
      implications; our hypothesis is that low concentrations of antigraft antibodies
      may mediate these changes. METHODS: In vitro cultured primary and immortalized
      porcine EC were incubated with polyclonal human IgG for 6 days and then examined
      for phenotype changes. RESULTS: The cells acquired resistance to tumor necrosis
      factor-alpha-mediated apoptosis (50-100% reduction at 6 hr) and up-regulated
      expression of Bcl-2 and Bcl-xl; sustained expression was accompanied by inducible
      nitric oxide (NO) synthase expression and by enhanced production of NO by EC. Two
      observations suggested that NO was actively involved in the process of Bcl-2 and
      Bcl-xl induction. First, (z)-1-2-[2-aminoethyl)-N- (2-ammonioethyl)amino]diazen-1
      ium-1,2-diolate, an NO donor, was able to induce similar changes in porcine EC to
      those induced by anti-pig antibodies. Second, an NO synthase inhibitor NG
      monomethyl-L-arginine.monoacetate was able to specifically inhibit the anti-pig
      antibody-mediated expression of Bcl-2 or Bcl-xl. CONCLUSIONS: These data strongly
      support the hypothesis that Bcl-2 and Bcl-xl expression and protection from
      apoptosis in EC may result from antibody-mediated NO production through the
      neoexpression of inducible NO synthase.

PMID- 11292288
TI  - CD8+ T cell subsets TC1 and TC2 cause different histopathologic forms of murine
      cardiac allograft rejection.
AB  - BACKGROUND: CD4+ T cell effector function is sufficient to mediate allograft
      rejection, and it is suggested that CD8+ T cell-mediated effects are dependent on
      CD4+ T cell help. CD8+ T cells can be classified into at least two functional
      subsets: Tc1, producing high amounts of interferon (IFN)-gamma and Tc2, producing
      interleukin (IL)-4, -5, -10, and -13 and low levels of IFN-gamma. Because these
      subsets express different chemokine receptors, they may have different
      capabilities of migrating into grafts. Once in the graft, each subset may perform
      different effector functions dependent on the cytokines it produces. We asked
      whether allospecific CD8+ T cells, in the absence of CD4+ T cells, are capable of
      mediating rejection of a primarily vascularized allograft, and if Tcl and Tc2
      cells differ in their ability to mediate rejection. METHODS: Hearts from H-2d
      mice were transplanted into H-2b RAG 1-/- recipients. Without manipulation, these
      fully mismatched allografts would survive indefinitely due to the absence of
      mature T and B cells. We adoptively transferred allo-(H-2d)-reactive Tcl or Tc2
      cells from H-2b mice into each recipient. Grafts were harvested and analyzed on
      predefined timepoints, rejection was graded on a modified ISHLT scale. RESULTS:
      On day 7, grafts from Tc1- or Tc2-injected animals showed grade 1-2 parenchymal
      rejection with stable phenotype and comparable distribution of graft infiltrating
      CD8+ T cells. Adoptive transfer of IFN-gammahigh Tc1, but not of IFN-gammalow Tc2
      cells was followed by the development of graft vasculitis, as well as graft
      arteriopathy. Adoptive transfer of IL-4high IL-5high Tc2, but not of IL-4low IL
      5low Tc1 cells lead to extensive infiltration of eosinophils and formation of
      giant cells. CONCLUSIONS: Both Tc1 and Tc2 cells can mediate murine cardiac
      allograft rejection in the absence of CD4+ T cell help, although each subset
      elicits a different type of inflammatory response. In this model, cytokine
      secretion of either functional CD8+ T effector cell subset is an important
      effector mechanism in the process of allograft rejection: IFN-gammahigh Tc1 cells
      are important in early graft vasculitis, although IL-4high IL-5high Tc2 cells
      promote recruitment of secondary effectors like eosinophils.

PMID- 11292289
TI  - Bone marrow transplant conditioning intensified with liposomal clodronate to
      eliminate residual host antigen presenting cells fails to ameliorate GVHD and
      increases PERI-BMT mortality.
AB  - BACKGROUND: Graft versus host disease (GVHD) mediated by allogeneic donor T cells
      may be initiated and/or exacerbated by residual host antigen presenting cells
      (APC) which survive the transplant conditioning regimen. We examined whether the
      depletion of hepatic and splenic APC could reduce the severity of hepatic GVHD
      after bone marrow transplantation (BMT). METHODS: Recipient mice were depleted
      for hepatic and splenic phagocytic APCs by i.v. injection of clodronate-
      (dichloromethylene diphosphonate) containing liposomes before fully allogeneic or
      MHC-matched, minor Ag-mismatched BMT. Severity of hepatic GVHD was scored on
      histological sections 2, 3, 4, or 9 weeks after BMT. RESULTS: No differences in
      the severity of GVHD were observed between APC-depleted mice and control mice.
      APC-depleted mice had increased peritransplant mortality due to sepsis. Bacterial
      clearance assays showed that APC-depleted mice were unable to efficiently clear
      bacteria, although nondepleted, transplanted mice were able to clear bacteria as
      quickly as naive control mice. CONCLUSIONS: Residual host phagocytic APC do not
      appear to play a role in the induction of GVHD after BMT. They are, however,
      essential for prevention of sepsis in the transplant host.

PMID- 11292290
TI  - Endotelin ETA and ETB receptor antagonism during cold preservation in renal
      transplantation.
AB  - BACKGROUND: In this study, we investigated the effects of selective endothelin
      (ET) receptor antagonism during different periods of cold ischemia on glomerular
      and tubular function and long-term survival in renal transplantation. METHODS:
      Left renal transplantation was performed in Lewis rats after 2 hr of cold
      ischemia without (n=8) and with (n=6) ETA receptor antagonism and after 16 hr of
      cold ischemia without treatment (n=6), with ETA receptor antagonism (n=8) and
      with ETB receptor antagonism (n=6). A control group (n=8) underwent right
      nephrectomy and left renal denervation. The ETA and ETB receptor antagonists (BQ
      610 and A-192621, respectively) were added to the preservation solution
      (EuroCollins). After transplantation, renal glomerular and tubular functions were
      monitored for up to 60 days or death. RESULTS: All animals in the control and 2
      hr groups survived the follow-up protocol, with early postoperative recovery of
      glomerular and tubular function while the entire untreated 16-hr group died
      between day 3-6 postoperatively. BQ-610 treatment had no measurable effect on the
      renal function in the 2-hr group, however, it improved glomerular and tubular
      functions and led to 50% long-term survival (60 days) in the 16-hr group. A
      192621 treatment had no effect on long-term survival or renal parameters.
      CONCLUSION: ETA receptor antagonism had protective renal effects after prolonged
      ischemic preservation in renal transplantation while ETB receptor antagonism had
      not.

PMID- 11292291
TI  - Effect of pre-and postoperative plasmapheresis on posttransplant recurrence of
      focal segmental glomerulosclerosis in children.
AB  - BACKGROUND: Posttransplant recurrence is frequent in patients who received renal
      transplantation for focal segmental glomerulosclerosis (FSGS). The recurrence has
      been ascribed to a circulating permeability factor or factors. We have used
      plasmapheresis (PP) to treat recurrent FSGS and also studied whether preoperative
      PP is effective in preventing recurrence of FSGS. METHODS: We retrospectively
      analyzed 21 allografts of 20 patients with nephrotic syndrome and biopsyproven
      FSGS. They were divided into two groups depending on whether they had
      prophylactic PP; a prophylactic (n=15) and a nonprophylactic group (n=6). PP was
      performed two to three times prophylactically and therapeutically until
      proteinuria was markedly reduced. In each session, 50-75 ml/kg of the patient's
      plasma was exchanged with 5-8% albumin. RESULTS: FSGS recurred in 9 of 21
      allografts, 4 of 6 in the nonprophylactic group, and 5 of 15 in the prophylactic
      group. Therapeutic PP was performed in seven of nine recurrent patients without
      definite adverse effect, with satisfactory results except in one patient.
      Children lost proteinuria after 6 to > 100 sessions of PP and the number
      correlated with the pretreatment level of proteinuria. The mean follow-up periods
      were 62.7 and 41.6 months for the prophylactic and nonprophylactic groups,
      respectively. At the last follow-up, 66.7% of relapsing and 81.8% of nonrelapsing
      patients had a functioning graft. CONCLUSION: PP appears to be effective for the
      prevention and treatment of posttransplant recurrence of FSGS, although further
      consideration of cost/benefit and risks is required before a conclusive judgement
      can be made.

PMID- 11292292
TI  - Orthotopic liver transplantation for mitochondrial respiratory chain disorders: a
      study of 5 children.
AB  - BACKGROUND: Liver involvement in mitochondrial respiratory chain disorders (MRCD)
      frequently ends in liver failure and death. Because of the high risk of
      extrahepatic, particularly neuromuscular, manifestations of the disease, the
      indication of orthotopic liver transplantation (OLT) in these patients remains
      controversial. We report on 5 such children in whom OLT was carried out, in an
      attempt to help clarify the matter. PATIENTS: Patients 1 and 2 presented with
      fulminant liver failure at ages 7 and 6 months respectively. Emergency liver
      transplantation was performed before etiological investigations were completed.
      Retrospective examination of the explanted livers showed defects in complexes I,
      III and IV. In patient 1, severe neurological deterioration occurred 2 months
      after OLT with fatal outcome 9 months later. Patient 2 is alive 22 months after
      OLT with moderate motor impairment. Patients 3, 4 and 5 presented with
      progressive liver failure before 6 months of age. Surgical liver biopsies
      displayed a 50% defect in complex IV (patient 3), a defect in complexes I, IV
      (patient 4) and in complexes I, III, IV (patient 5). Because there was no
      clinical extrahepatic involvement on investigations, OLT was carried out in these
      patients. Patient 3 died of multiple organ failure soon after OLT, patients 4 and
      5 are alive respectively 21 months and 12 months after OLT with normal
      neurological examination. CONCLUSION: OLT may be a valid therapeutic option in
      infants with delayed liver cell failure due to MRCD, only after performing in
      emergency a thorough inves tigation to exclude clinically significant
      extrahepatic, especially neuromuscular, involvement.

PMID- 11292293
TI  - Mycophenolate mofetil in pediatric renal transplantation without induction
      therapy: results after 12 months of treatment. German Pediatric Renal
      Transplantation Study Group.
AB  - BACKGROUND: Acute rejection episodes (ARE) of kidney transplants are considered
      as risk factor in the development of chronic rejection. In adult renal
      transplantation (RTx), ARE have been significantly reduced by mycophenolate
      mofetil (MMF) in combination with cyclosporin (CyA) and steroids (Pred). Reports
      of pediatric RTx on a maintenance immunosuppression with MMF are restricted to
      patients (P) after antibody induction therapy. METHODS: The efficacy and safety
      of MMF combined with CyA and Pred in pediatric RTx without induction therapy were
      evaluated in an open-labeled multicenter study. RESULTS: From 10/1996 to 6/1999,
      65 pediatric P (MMF group) were followed for at least 6 months, 58 of 65 for 12
      months. These P were compared with 54 retrospectively analyzed pediatric P who
      were transplanted between 1990 and 1996 and had received CyA, Pred, and
      azathioprine for immunosuppression (historic AZA group). Within the first 6
      months after RTx, 18 of 65 (MMF group) and 32 of 54 (historic AZA group) P showed
      clinical signs of acute rejection (P<0.01). Thereafter only one further P in the
      MMF group developed a first ARE. Graft loss due to rejection occurred in one MMF-
      and seven AZA-treated P (P<0.05). The creatinine-clearance 3 and 6 months after
      RTx was higher in the MMF group. Major adverse events (MMF group) included
      infections of the urinary and the upper respiratory tract, diarrhea, and
      leukopenia. Cytomegalovirus-infection occurred in 13 P and 2 P developed
      cytomegalovirus disease. One P developed PTLD 10 months after RTx and recovered
      after the reduction of immunosuppression. CONCLUSIONS: The combination of MMF,
      CyA, and Pred reduced ARE in pediatric RTx without incurring major side effects.

PMID- 11292294
TI  - Osteoporosis after renal transplantation: single center experience.
AB  - BACKGROUND: Osteoporosis is a major source of morbidity after renal
      transplantation. The aim of this retrospective study was to determine the
      independent influences of different parameters on bone mineral density (BMD) in
      various parts of the body after renal transplantation. METHODS: BMD was measured
      in 130 of 954 renal allograft recipients who underwent surgery between 1985 and
      1999. RESULTS: Time since transplantation and cumulative prednisolone doses were
      significantly higher in patients who had osteoporosis of the lumbar vertebrae
      (P=0.06 and 0.034, respectively). Logistic regression analysis revealed that
      cumulative prednisolone dose was the only significant predictor of low vertebral
      BMD (P=0.02, r=0.33). For the neck of the femur, high blood urea nitrogen and low
      Mg levels were found to be the predictors of low bone density (P=0.002 and 0.04,
      respectively). Although parathyroid hormone levels were higher in femoral
      osteoporosis patients than in those not affected at this site, the difference was
      not statistically significant (P=0.294). Time since transplantation, cumulative
      prednisolone dose, and cyclosporine A dose were all found to have a major
      negative impact on BMD in the radius region (P=0.001, 0.000, 0.001,
      respectively). Regression analysis showed that cumulative prednisolone dose
      (P=0.0008, r=0.34), time since transplantation (P=0.005, r=0.27), body mass index
      (P=0.01, r=-0.21), male gender (P=0.02, r=-0.21), and age (P=0.04, r=0.16) all
      had major effects on radius BMD. In conclusion, the radius seems to be one of the
      major parts of the skeleton affected by factors introduced after renal
      transplantation.

PMID- 11292295
TI  - Hyperacute rejection in single lung transplantation--case report of successful
      management by means of plasmapheresis and antithymocyte globulin treatment.
AB  - We describe the third case and first successful treatment of hyperacute rejection
      in a pulmonary allograft recipient and detail the immediate clinical findings.
      The patient underwent single right lung transplantation for severe emphysema and
      chronic obstructive pulmonary disease. Three hours after completion of the
      vascular anatomoses oxygen desaturation and increased airway pressure was noted
      in combination with graft edema, frothy, pink fluid draining from the bronchial
      orifice, hemodynamic instability, thrombocytopenia, and coagulopathy. The
      retrospective cross-match result was reported to be positive. The clinical
      diagnosis of hyperacute rejection was made. A donor-specific IgG HLA antibody to
      A2 was identified. The standard immune suppression regimen was immediately
      modified and a hyperacute rejection protocol applied including plasmapheresis and
      antithymocyte globulin treatment as well as cyclophosphamide to decrease antibody
      existence and production. A remarkable clinical recovery was observed after the
      fifth postoperative day and completion of plasmapheresis when a repeated
      retrospective cross-match showed significantly decreasing anti-donor reactivity.

PMID- 11292296
TI  - Acute humoral rejection in renal allograft recipients: I. Incidence, serology and
      clinical characteristics.
AB  - BACKGROUND: Acute rejection (AR) associated with de novo production of donor
      specific antibodies (DSA) is a clinicopathological entity that carries a poor
      prognosis (acute humoral rejection, AHR). The aim of this study was to determine
      the incidence and clinical characteristics of AHR in renal allograft recipients,
      and to further analyze the antibodies involved. METHODS: During a 4-year period,
      232 renal transplants (Tx) were performed at our institution. Assays for DSA
      included T and B cell cytotoxic and/or flow cytometric cross-matches and
      cytotoxic antibody screens (PRA). C4d complement staining was performed on frozen
      biopsy tissue. RESULTS: A total of 81 patients (35%) suffered at least one
      episode of AR within the first 3 months: 51 had steroid-insensitive AR whereas
      the remaining 30 had steroid-sensitive AR. No DSA were found in patients with
      steroid-sensitive AR. In contrast, circulating DSA were found in 19/51 patients
      (37%) with steroid-insensitive AR, and widespread C4d deposits in peritubular
      capillaries were present in 18 of these 19 (95%). In at least three cases,
      antibodies were against donor HLA class II antigens. DSA were not found in the
      remaining 32 patients but C4d staining was positive in 2 of 32. The DSA/C4d
      positive (n=18) and DSA/C4d negative (n=30) groups differed in pre-Tx PRA levels,
      percentage of re-Tx patients, refractoriness to antilymphocyte therapy, and
      outcome. Plasmapheresis and tacrolimus-mycophenolate mofetil rescue reversed
      rejection in 9 of 10 recipients with refractory AHR. CONCLUSION: More than one
      third of the patients with steroid-insensitive AR had evidence of AHR, often
      resistant to antilymphocyte therapy. Most cases (95%) with DSA at the time of
      rejection had widespread C4d deposits in peritubular capillaries, suggesting a
      pathogenic role of the circulating alloantibody. Combined DSA testing and C4d
      staining provides a useful approach for the early diagnosis of AHR, a condition
      that often necessitates a more intensive therapeutic rescue regimen.

PMID- 11292297
TI  - Serum cholesterol levels and kidney transplantation outcome: attenuation of
      cyclosporine efficacy?

PMID- 11292298
TI  - Should the indications for laparascopic live donor nephrectomy of the right
      kidney be the same as for the open procedure? Anomalous left renal vasculature is
      not a contraindiction to laparoscopic left donor nephrectomy.
AB  - BACKGROUND: The left kidney is preferred for live donation. In open live donor
      nephrectomy, the right kidney is selected if the left kidney has multiple renal
      arteries or anomalous venous drainage. With laparoscopic live donor nephrectomy
      (LLDN), there is reluctance to procure the right kidney because of the more
      difficult exposure and further shortening of the right renal vein (RRV) after a
      stapled transection. An experience with LLDN is reviewed to determine whether the
      right kidney should be procured laparoscopically. METHODS: From February 1995 to
      November 1999, 227 patients underwent live donor renal transplants with
      allografts procured by LLDN. The results of these transplants were analyzed.
      RESULTS: Of the 227 kidneys transplanted, 17 (7.5%) were right kidneys. In the
      early experience, three (37.5%) of the eight right renal allografts developed
      venous thrombosis, two of which had duplicated RRV. Based on these initially
      unacceptable results, donor evaluation and LLDN techniques were modified. Spiral
      computerized tomography (CT) replaced conventional angiography to define better
      the venous anatomy. LLDN was modified in one of three ways: (1) changing the
      stapler port placement such that the RRV was transected in a plane parallel to
      the inferior vena cava, (2) relocation of the incision for open division of RRV,
      or (3) lengthening of the donor RRV with a panel graft constructed of recipient
      greater saphenous vein. Finally, the recipient operation enjoined complete
      mobilization of the left iliac vein with transposition lateral to the iliac
      artery. With these modifications, there were no vascular complications with the
      subsequent nine right renal allografts (P<0.05). Of the left kidneys
      transplanted, 31 had multiple renal arteries, 14 had retroaortic or circumaortic
      veins, 4 had both multiple arteries and venous anomalies, and 1 had a duplicated
      IVC draining the left renal vein. There were no vascular complications with left
      renal allografts that had multiple arteries or venous anomalies. CONCLUSIONS:
      LLDN of the left kidney is technically easier. Left kidneys with multiple
      arteries or anomalous venous drainage are not problematic. The right kidney can
      be procured with LLDN; however, a rational approach to preoperative angiographic
      imaging, donor operation, and recipient operation is crucial.

PMID- 11292299
TI  - De novo hepatitis with autoimmune antibodies and atypical histology: a rare cause
      of late graft dysfunction after pediatric liver transplantation.
AB  - BACKGROUND: Late graft dysfunction after orthotopic liver transplantation is
      commonly due to chronic rejection, recurrence of primary disease, sepsis, lympho
      proliferative disease, or vascular or biliary complications. Herein we describe a
      subset of pediatric liver transplant patients in whom late graft dysfunction was
      associated with autoimmune markers, bile ductular proliferation, and portal
      infiltrates, which progress to fibrosis. This subset of patients has not been
      previously described. METHODS: Six of the 115 children followed for greater than
      5 years after transplantation developed this unusual form of graft dysfunction.
      All children were on a low-dose single immunosuppressive therapy (mean trough
      cyclosporine concentration 89 microg/L) and had been tapered off steroids for a
      median duration of 1.5 year. Liver biopsies were performed in all children to
      evaluate the graft dysfunction, and the histologic findings were interpreted by
      an experienced hepato-pathologist. All patients were tested for antibodies to
      hepatitis C virus, hepatitis B surface antigen, and IgM antibodies to hepatitis
      A. Smooth muscle antibody, antinuclear antibody, and antibody to liver/kidney
      microsome type 1 were sought by indirect immunofluorescence. International
      Autoimmune Hepatitis Group scores were calculated. All patients underwent
      ultrasonography with doppler studies at the onset of graft dysfunction. Three
      patients with marked bile duct proliferation on histology had cholangiograms.
      RESULTS: Histology in all patients showed mononuclear cell infiltrates in the
      portal area with interface hepatitis, portal fibrosis, and ductular proliferation
      without duct damage or loss. All six patients had positive antinuclear antibody
      or smooth muscle antibody titers. Viral studies for hepatitis A, B, and C were
      negative in all patients. On the International Autoimmune Hepatitis Group scoring
      system, five patients had probable autoimmune hepatitis (score of 10-15) and one
      had definite autoimmune hepatitis (score > 15) at the onset of graft dysfunction.
      All were treated with azathioprine and prednisone similar to treatment for
      autoimmune hepatitis. However, despite aggressive treatment, four patients
      developed bridging portal fibrosis resulting in graft loss in two patients.
      CONCLUSION: This clinical constellation is associated with worse outcome then
      that previously described for pediatric patients with posttransplantation de novo
      autoimmune hepatitis. Further studies are needed to find an optimal treatment
      regimen for these patients.

PMID- 11292300
TI  - Treatment of established bone loss after renal transplantation with etidronate.
AB  - BACKGROUND: Osteoporosis is a well-documented complication of organ
      transplantation. Bisphosphonates have been shown to be effective in preventing
      corticosteroid-induced osteoporosis in renal transplant recipients, but data are
      lacking for treatment of established osteoporosis. This study reports our
      clinical experience of treatment with the bisphosphonate etidronate in a single
      renal transplant center. METHODS: To establish the effectiveness of etidronate in
      treating established low bone mineral density (BMD), all newly transplanted
      patients treated with etidronate were compared with controls. Twenty-five
      patients treated with etidronate (14 males, 11 females) and 24 controls (15
      males, 9 females) were identified from the cohort of patients who underwent
      transplantation between January 1, 1994, and December 31, 1996. RESULTS: There
      was no difference in mean age, weight, or cumulative dose of corticosteroids
      between the treatment and control groups. The baseline BMD measurement was
      performed at 10.4 +/- 5.3 months after transplantation for treated patients and
      at 10.7 +/- 4.5 months for controls (P=0.78). Over the subsequent 1-year study
      period, patients treated with etidronate demonstrated a greater increase in BMD
      at sites with a preponderance of trabecular bone. Lumbar spine BMD increased 4.3
      +/- 6.1% in the treatment group versus 0.55 +/ -5.3% in controls (P<0.03) and
      trochanter BMD increased 10.3 +/- 11.9% and 2.2 +/- 5.7%, respectively, in the
      treatment and control groups (P<0.02). CONCLUSIONS: This study establishes the
      effectiveness of etidronate for treatment of low BMD in renal transplant
      recipients. Patients selected for treatment had lower baseline BMD than control
      subjects, yet still showed a clinically important increase in BMD.

PMID- 11292301
TI  - Association of polymorphisms in the human interferon-gamma and interleukin-10
      gene with acute and chronic kidney transplant outcome: the cytokine effect on
      transplantation.
AB  - BACKGROUND: Our group has previously described five different size alleles of an
      interferon (IFN)-gamma microsatellite. Analyzing this polymorphism, this study
      correlated high IFN-gamma production with a 12 CA repeat allele (allele 2).
      Further, our group has described interleukin (IL)-10 polymorphism defining in
      vitro high and low IL-10 producer status. METHODS: Samples from 88 of 115
      consecutive cadaveric renal transplants were used to define polymorphism of both
      IFN-gamma and IL-10. Patients were separated into high and low genotypes based on
      the previously reported association between certain genotypes and in vitro
      production. Graft survival, acute rejection, and serum creatinine at 5 years were
      analyzed for comparison between groups. RESULTS: The genotype associated with
      high IFN-gamma production was found in 70 patients. The incidence of acute
      rejection was 54.3% in the high IFN-gamma genotype group, compared with 44.4% in
      the low IFN-gamma group. Requirement for antithymocyte globulin therapy was
      greater in the high IFN-gamma group (odds ratio [OR]=2.5). Among HLA-DR
      mismatched patients, IFN-gamma genotype was more strongly associated with
      rejection (OR=2.86). In the cyclosporine monotherapy subgroup, patients with high
      IFN-gamma genotype had a 61% incidence of rejection compared with only 20% in the
      low IFN-gamma genotype patients (OR=3.06). Graft survival was similar between the
      two groups. When the analysis was controlled for the presence of delayed graft
      function, 40.5% of the high IFN-gamma genotype patients had serum creatinine
      levels above 200 micromol/L compared with only 14.3% of the low IFN-gamma
      genotype recipients at 5 years after transplantation (P=0.05). The high IL-10
      genotype was shown to be associated with better graft function at 5 years (75 vs.
      50%, P=0.09). CONCLUSION: In this study we have shown that high producer genotype
      for IFN-gamma may have an influence on acute rejection of kidney transplants,
      particularly in patients on cyclosporine monotherapy. It is also associated with
      worse long-term graft function. On the contrary high IL-10 production may have a
      long-term protective effect.

PMID- 11292302
TI  - Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after
      liver transplantation.
AB  - BACKGROUND: Initial studies utilizing interferon-alpha and ribavirin for the
      treatment of recurrent hepatitis C virus (HCV) infection after liver
      transplantation showed promising results. Here we report our single-center
      experience using this combination therapy. METHODS: Liver transplant recipients
      with recurrent HCV (elevated serum aminotransferases, positive serum HCV RNA, and
      biopsy-proven hepatitis without rejection) received interferon-alpha (1.5-3
      million units subcutaneously three times a week) and ribavirin (400-1000 mg p.o.
      daily) for 12 months or more. Serum aminotransferases, HCV RNA, and severity of
      hepatitis were followed. RESULTS: Thirty-two patients have been treated for at
      least 3 months, including 13 who have been on 12 or more months of therapy. Three
      died from allograft failure due to recurrent HCV. Dose reductions of interferon
      alpha and/or ribavirin occurred in 22 patients. Thirteen had their medications
      permanently discontinued for severe adverse effects. Twenty-six patients (81%)
      had a biochemical response (BR; normalization of serum aminotransferases) after 3
      months. End-of-treatment and sustained BR were 77% and 71%, respectively. Mean
      viral loads decreased 68-77%; however, only three patients became serum HCV RNA
      negative. After 12 months of therapy, no histological improvement was observed in
      11 patients who were biopsied. Patients who received mycophenolate mofetil or
      daclizumab had a less likelihood of achieving a BR. CONCLUSIONS: A significant
      number of patients did not tolerate interferon-alpha or ribavirin. Although BR
      was excellent and mean viral loads decreased significantly, virological clearance
      was poor and no histological improvement was noted. A more efficacious treatment
      with less adverse effects for recurrent HCV after liver transplantation is
      needed.

PMID- 11292303
TI  - Prolongation of allograft survival with viral IL-10 transfection in a highly
      histoincompatible model of rat heart allograft rejection.
AB  - BACKGROUND: The ability to express genes with potential immunoregulatory capacity
      could reduce the immunogenicity of allografts and result in long-term graft
      survival. In this study, we examine the feasibility of transferring viral
      interleukin-10 (vIL-10) gene into rat hearts using adenovirus by intracoronary
      administration. The subsequent effects of delivered vIL-10 alone or with
      subtherapeutic doses of cyclosporine A (CsA) on parameters of allograft rejection
      (AR) were also examined. METHODS: Recombinant adenovirus vectors containing vIL
      10 (Ad-vIL-10) or beta-galactosidase (Ad-beta-gal) were derived from adenovirus
      type 5. vIL-10 expression in supernatants of transfected COS7 cell cultures and
      in transfected heart allografts were examined by enzyme immunoassay (EIA) and
      reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Rat heart
      transplants (LEWS->ACI) were performed in five groups [group 1: no treatment,
      group 2: Ad-beta-gal, group 3: AdvIL-10, group 4: CsA (10 mg/kg), and group 5: Ad
      vIL10+CsA (10 mg/kg)]. Allograft survival was determined by palpating heartbeats.
      Allograft tissues were also submitted for histological study. RESULTS: vIL-10
      expression was shown in both transfected COS7 cells and heart isografts. Animals
      transfected with vIL-10 showed prolongation of graft survival (19.6 vs. 12 days,
      P<0.001) when compared to beta-gal transfected controls. Animals treated with a
      single low dose injection of CsA showed no significant prolongation of graft
      survival compared to controls (11.7 vs. 10.5 days). Animals treated with both vIL
      10 and CsA demonstrated a synergistic prolongation of allograft survival compared
      with controls and with animals treated with CsA or vIL-10 treatment alone (36.7
      days vs. 11.7, P<0.001 or 36.7 vs.19.6, P<0.001, respectively). Histological
      study showed that allografts from untreated controls exhibited extensive AR with
      loss of graft architecture by day 7 posttransplant while those from the vIL-10
      group showed less AR. The best pathological scores were seen in vIL-10 + CsA
      treated animals. CONCLUSIONS: 1) Delivering Ad-vIL-10 into donor hearts by
      intracoronary perfusion results in overexpression of vIL-10 and significantly
      prolongs cardiac allograft survival in a highly histoincompatible rat model. 2)
      Subtherapeutic doses of CsA do not prolong allograft survival, but act
      synergistically with vIL-10 to significantly prolong graft survival beyond that
      achieved with either agent alone.

PMID- 11292304
TI  - Increased costimulatory responses in African-American kidney allograft
      recipients.
AB  - BACKGROUND: The issue of racial differences in immune responses has been seldom
      investigated, despite the increased incidence of transplant rejection and
      inferior allograft outcomes in African-Americans (AA). We previously reported
      significantly increased expression of costimulatory molecules on peripheral blood
      cells from healthy adult AA compared with Caucasian (CS) volunteers. This report
      extends the study to pediatric kidney allograft recipients. METHODS: Surface
      antigen expression by peripheral blood mononuclear cells (MNC) from AA and CS
      transplant patients was determined by flow cytometry, after staining with
      specific antibodies. In vitro proliferation, in a one-way mixed lymphocyte
      response (MLR), was measured after stimulation with allogeneic irradiated
      mononuclear cells. The concentration of cyclosporine (CsA) achieving 50%
      inhibition (IC50) of in vitro proliferative responses to PHA and OKT3 was
      calculated. RESULTS: MNC from AA patients were shown to have significantly higher
      expression of CD80 (CS 5.2% +/- 0.6, AA 9.6% +/- 1.2, P < 0.0001) than cells from
      CS patients. Additionally, the cells from AA transplant recipients proliferated
      significantly more in an MLR (stimulation index: CS 8 +/- S2, AA 25 +/- 8, P <
      0.05), and the CsA IC50 values, during proliferation to PHA and OKT3, were
      significantly higher in AA compared to CS patients. CONCLUSIONS: Although
      socioeconomic factors and therapeutic compliance are undoubtedly important issues
      in long-term allograft survival, our data suggest that AA patients mount more
      vigorous immune responses to antigens. The increased requirement for
      immunosuppression may be linked to racial variations in costimulatory molecule
      expression on antigen-presenting cells.

PMID- 11292305
TI  - "Pseudoseptic" pseudogout associated with hypomagnesemia in liver transplant
      patients.
AB  - Hypomagnesemia has been associated with deposition of calcium pyrophosphate
      dihydrate crystals in articular structures, causing pseudogout, also known as
      calcic gout. Occasionally, pseudogout may mimic septic arthritis; this
      "pseudoseptic" attack may be of especial concern in the immunocompromised host,
      such as transplant recipient patients, who may be indeed at risk of developing
      septic arthritis. We report the cases of two patients in whom pseudogout
      developed after liver transplantation. Synovial fluid appearance and leukocyte
      counting in synovial fluid mimicked septic arthritis, but calcium pyrophosphate
      dihydrate crystals were observed. Magnesium depletion before transplantation and
      further tacrolimus-induced renal magnesium leakage were probably working in these
      patients.

PMID- 11292306
TI  - May-Thurner syndrome in renal transplantation.

PMID- 11292307
TI  - Fas mRNA expression in blood is reduced during episodes of human corneal graft
      rejection.
AB  - BACKGROUND: Our purpose is to examine levels of Fas mRNA expression in blood
      during human corneal transplant rejection. METHODS: Fas mRNA expression was
      detected by reverse transcription-PCR in blood from normal controls, corneal
      recipients at the time of transplantation and during episodes of rejection.
      RESULTS: Samples taken at the time of a corneal rejection episode showed Fas mRNA
      levels were significantly lower in these patients than either normal controls (P
      = 0.017) or corneal transplant recipients not undergoing graft rejection (P =
      0.00052). Serial samples from five patients who suffered an episode of rejection
      showed that the level of Fas mRNA is reduced during the rejection episode and
      subsequently recovers. CONCLUSIONS: These results indicate low levels of Fas mRNA
      in blood may have a role in corneal transplant rejection.

PMID- 11292308
TI  - Perceptual priming for upright and inverted faces in infants and adults.
AB  - Based on recent models of the ontogeny of memory (Nelson, 1995), we hypothesize
      that 6-month-old infants should show evidence of repetition priming. Event
      related potentials were recorded from 11 scalp sites to novel and primed upright
      and inverted faces. In Experiment 1 (n = 24), 6-month-old infants viewed faces
      that were repeated after 6 to 12 images. Overall, repeated faces demonstrated
      greater negativity than novel faces and upright faces demonstrated greater
      negativity than inverted faces. In order to ground these results in an adult
      model, a group of adults (n = 30) was tested in a similar experiment. Here we
      observed effects of repetition at an early positive component labeled the P150 as
      well as at the P300, with repeated images being more positive than novel images.
      These data support the idea that infants at 6 months are capable of revealing
      electrophysiological evidence of perceptual priming.

PMID- 11292309
TI  - Kindergartners' understanding of additive commutativity within the context of
      word problems.
AB  - Baroody and Gannon (1984) proposed that children's understanding of additive
      commutativity progresses through several levels of understanding based on a unary
      view of addition (change meaning) before developing a "true" level of
      understanding based on a binary conception (part-whole meaning). Resnick (1992)
      implied that children have both a unary and a binary conception of additive
      commutativity from the earliest stages of development. Fifty-three 5- and 6-year
      old (M = 6-0) kindergartners' unary and binary understanding of additive
      commutativity was investigated using performance on tasks involving change-add-to
      and part-part-whole word problems, respectively. The data were inconsistent with
      the predictions of both models and suggest three alternate theoretical
      explanations. Moreover, the data indicate that success on a task involving change
      add-to problems may be a more rigorous test of understanding of additive
      commutativity than that involving part-part-whole problems.

PMID- 11292310
TI  - Learning multiplication facts: a study of children taught by discovery methods in
      England.
AB  - The development of multiplication skills was examined in a group of children ages
      8 to 12 years who were taught by discovery methods. Strategies used by the
      children included direct retrieval, retrieval + calculation, and counting-in
      series. Repeated addition was not observed. Retrieval was the fastest and least
      error-prone strategy; counting-in-series was the slowest and most error prone.
      Children ages 8 and 9 years used mainly mixed strategies. Children ages 10 to 12
      years used mainly retrieval or retrieval and calculation for low operands, but
      reverted to back-up strategies for high operands based on the strategies
      available for low operands. There was a general shift away from less effective
      strategies across ages 8 to 12 years but, by the end of the primary school (age
      11 years), relatively few children used the most effective strategy of retrieval
      for all operands. The development of effective strategies was related to
      nonverbal reasoning ability and to working memory capacity. The results are
      considered with reference to experiential and pedagogical models of
      multiplication.

PMID- 11292311
TI  - Learning a novel grapheme: effects of positional and phonemic context on
      children's spelling.
AB  - Two experiments explored how children who encounter a new spelling for a phoneme
      generalize it to novel items. Children ages 5 1/2 to 9 (N = 123) were taught a
      CVC (consonant-vowel-consonant) nonword containing a new vowel spelling in the
      middle position (e.g., /gaik/ is spelled as giik). They were then asked to spell
      other nonwords containing the vowel or to judge spellings that had supposedly
      been produced by younger children. Children were sensitive to position in the
      spelling production task, being more likely to use the novel grapheme when the
      vowel appeared in the middle of a CVC target than when it appeared in word
      initial or word-final position. Children were not significantly more likely to
      use the novel grapheme when the target shared the vowel and final consonant
      (rime) of the training stimulus than when it shared the initial consonant and
      vowel. Implications for views of spelling development are discussed.

PMID- 11292312
TI  - Perceptual categorization of cat and dog silhouettes by 3- to 4-month-old
      infants.
AB  - Given evidence that silhouette information can be used by adults to form
      categorical representations at the basic level, four experiments utilizing the
      familiarization-novelty preference procedure were performed to examine whether 3-
      and 4-month-old infants could form categorical representations for cats versus
      dogs from the perceptual information available in silhouettes (e.g., global shape
      and external outline). Experiments 1 and 2 showed that infants could form
      individuated categorical representations for cat and dog silhouettes, whereas
      Experiments 3 and 4 revealed that infants could use silhouette information from
      the head, but not the body, to categorically separate the two species. These
      results indicate that general shape or external contour information that is
      centered about the head is sufficient for young infants to form individuated
      categorical representations for cats and dogs. The data thus provide information
      regarding the nature of the perceptual information that can be used by infants to
      form category representations for individual animal species and are discussed in
      terms of domain-general versus domain-specific processing accounts.

PMID- 11292313
TI  - Children's ability to make tentative interpretations of ambiguous messages.
AB  - Consistent with prior research, 5- and 6-year-old children overestimated their
      knowledge of the intended referent of ambiguous messages. Yet they correctly
      revised their interpretations of ambiguous messages in light of contradicting
      information that followed immediately, while maintaining their initial
      interpretations of unambiguous messages (Experiment 1). Children of this age were
      able to integrate information over two successive ambiguous messages to identify
      the intended referent (Experiment 2). However, unlike 7- and 8-year-olds, they
      were no more likely to search for further information following ambiguous
      messages compared with unambiguous ones (Experiment 3). We conclude that although
      5- and 6-year-olds' interpretations of ambiguous messages are not tentative at
      the outset, they can use source monitoring skills to treat them as tentative
      retrospectively, at least over short time spans.

PMID- 11292314
TI  - Mutational analysis of chicken interleukin 2.
AB  - Chicken interleukin 2 (chIL-2) has low, but significant, homology to both
      mammalian IL-2 and mammalian IL-15. In view of its unique phylogenetic position
      and potential use as a vaccine adjuvant, a detailed mutational analysis for
      critical functional sites was undertaken. It was found that Asp17 is a critical N
      terminal contact site for binding to the putative chIL-2 receptor, which is
      similar to results obtained for mammalian IL-2 and IL-15. Analysis of the C
      terminus did not reveal a single critical amino acid. However, deletion mutant
      studies demonstrated that removal of C terminal amino acids yielded proteins with
      decreased bioactivity and that this decrease was a function of the number and
      kind of amino acids removed. This study is the first non-mammalian IL-2
      mutational analysis and proposes a model for the interaction between chIL-2 and
      its receptor.

PMID- 11292315
TI  - Macrophage-derived chemokine gene expression in human and macaque cells: mRNA
      quantification using NASBA technology.
AB  - Macrophage-derived chemokine (MDC) is a CC-chemokine that inhibits infection by
      both macrophage- and T cell-tropic strains of HIV-1. This suppressor activity has
      led to great interest in fully characterizing the role of MDC in the pathogenesis
      of HIV-1 infection. Methods for the quantitation of constitutive levels of MDC
      protein in vivo are lacking. In this report, we describe the development and
      performance of a NASBA-based assay for the quantification of MDC mRNA expression
      in human and macaque cells. Although the constitutive in vivo levels of MDC mRNA
      in macaque and human T lymphocytes were low, in vitro activation of these cells
      greatly increased MDC transcription. Levels in the human and macaque cells were
      comparable under all conditions tested. Positive correlations between MDC
      transcription and protein expression were observed. The results indicate that
      this assay is extremely sensitive and reproducible over a five log dynamic range,
      and effectively quantifies MDC mRNA in resting and activated T cells. This assay
      may therefore permit characterization of the role of MDC in HIV-1/SIV
      pathogenesis, and in vaccine-induced immune responses.

PMID- 11292316
TI  - Hypoxia induces the expression and release of interleukin 1 receptor antagonist
      in mitogen-activated mononuclear cells.
AB  - Hypoxia modulates the expression of inflammatory mediators in a variety of cell
      types. Since interleukin (IL-)1 receptor antagonist (Ra) is a cytokine widely
      associated with an inflammatory state and is expressed by activated mononuclear
      cells, we investigated whether hypoxia induces IL-1Ra expression in human
      peripheral blood mononuclear cells (PBMC) activated by phytohaemagglutinin (PHA).
      RNase protection assay, conducted on PHA-activated PBMC cultured under hypoxic
      conditions (2% O(2)) for 16-40 h, revealed that hypoxia enhances IL-1Ra mRNA
      expression. Further, IL-1Ra release was significantly affected by hypoxia, as
      determined by ELISA. Concomitantly, hypoxia enhanced, even though at a lesser
      extent, both IL-1alpha and IL-1beta mRNA expression and release, as determined by
      RPA and ELISA. However, at 40 h of treatment, hypoxia did not affect cell
      viability and DNA fragmentation, but caused an inhibition of the proliferation
      index after PHA stimulation, obtained by MTT assay. These results suggest that
      activated mononuclear cells tend to respond to hypoxic stress by modulating the
      expression of IL-1Ra and IL-1-related molecules and their release in the
      surrounding microenvironment.

PMID- 11292317
TI  - Differentially expressed genes in L6 rat skeletal muscle myoblasts after
      incubation with inflammatory cytokines.
AB  - OBJECTIVE: The mechanism underlying exercise intolerance in chronic heart failure
      is still unclear. An increased concentration of inflammatory cytokines could be
      detected in the serum of patients with chronic heart failure (CHF) exhibiting a
      correlation with the severity of the disease. The variety of molecular
      alterations triggered by these cytokines in the skeletal muscle is almost
      unknown. The study was designed to analyze the differential gene expression in
      skeletal muscle myoblasts after stimulation with inflammatory cytokines. METHODS:
      L6 rat skeletal muscle myoblasts were incubated for 24 h with a combination of IL
      1beta/IFN-gamma and the differential gene expression profile was determined by a
      PCR-based subtractive hybridization method. RESULTS: Out of 173 picked clones 141
      different sequences could be identified. By comparison with Genebank, the
      identity of 73 genes (51.7%) could be confirmed, whereas the rest did not show a
      homology to any known gene. Some of the identified genes are known to be altered
      in patients with CHF. CONCLUSION: In summary, the results of this study provide
      information about changes in gene expression after exposure of skeletal muscle
      cells to inflammatory cytokines. This information may yield a new gene pool,
      worthwhile to be analyzed in skeletal muscle of patients with chronic heart
      failure.

PMID- 11292318
TI  - Cytokine-augmented culture of haematopoietic progenitor cells in a novel three
      dimensional cell growth matrix.
AB  - Studies aimed at the in vitro expansion of haematopoietic progenitor cells (HPCs)
      have suffered from the conflict of increasing cell numbers while maintaining long
      term repopulating ability. We have developed a long-term bone marrow bioreactor
      culture system resembling the marrow-microenvironment that cultures HPCs in an
      inert, three-dimensional, porous biomatrix termed Cellfoam. Previous studies have
      shown that the short-term culture of CD34(+)cells in Cellfoam improved the
      maintenance and multipotency of haematopoietic stem cells compared to cells
      cultured on plastic dishes. In this study, we examined the effects of low
      concentrations of cytokines including stem cell factor (SCF), IL-3, and Flk-2/Flt
      3 ligand, on the maintenance, preservation and multipotency of CD34(+) cells
      cultured for 3 or 6 weeks in Cellfoam. Analysis of cell yields using flow
      cytometry showed that in SCF and Flk-2/Flt-3 ligand-supplemented cultures as well
      as cytokine-free cultures, a higher number of CD45(+)34(+) and CD45(+)34(+)38(-)
      cells is observed in Cellfoam cultures as compared to plastic cultures. The
      function of cultured cells was evaluated in colony-forming assays. The data
      demonstrate that Cellfoam cultures supplemented with SCF and Flk-2/Flt-3 ligand
      resulted in a higher output of colony activity compared to plastic cultures.
      Analysis of CAFC (29 days) activity also demonstrated that primitive progenitors
      were maintained to a greater extent in Cellfoam cultures containing either no
      cytokines or low concentrations of early-acting cytokines. These data suggest
      that culture of HPCs in three-dimensional bioreactors such as Cellfoam for
      extended periods may benefit from the addition of low levels of early-acting
      cytokines, including SCF and Flk-2/Flt-3 ligand, resulting in high yields of
      cells that are enriched for multipotent haematopoietic progenitors. These
      findings demonstrate that a three-dimensional matrix promotes the survival of
      primitive HPCs in culture and may modulate the in vitro effects of cytokines.

PMID- 11292319
TI  - In vitro inhibitory effects of Daphne oleoides ssp. oleoides on inflammatory
      cytokines and activity-guided isolation of active constituents.
AB  - Aerial parts of Daphne oleoides Schreber ssp. oleoides (Thymelaeaceae) are used
      to treat rheumatoid arthritis and lumbago in Turkish folk medicine. In order to
      evaluate folkloric utilization, in vitro inhibitory effects of the ethyl acetate
      extract and fractions obtained from this extract on interleukin 1 (IL-1alpha, IL
      1beta) and tumour necrosis factor (TNF-alpha) biosynthesis were studied. Through
      chemical isolation techniques and activity-guided fractionation process,
      seventeen compounds were isolated and their structures were elucidated (numbered
      1-17). Diterpenoids genkwadaphnin (3) and 1,2-dehydrodaphnetoxin (6) and a
      coumarin derivative daphnetin (9) showed potent inhibitory activity and were
      found to be the main active ingredients. Furthermore, gnidilatin (4), gnidilatin
      20 palmitate (5), genkwadaphnin-20-palmitate (7) and gnidicin-20-palmitate (8),
      having diterpenoid structure, and eudesmine (12), wikstromol (13) and
      matairesinol (14), having lignan structure, were determined to possess moderate
      inhibitory activity and may have a contributory role in the effect of the remedy.

PMID- 11292320
TI  - Identification of two U937 cell sublines exhibiting different patterns of
      response to tumour necrosis factor.
AB  - The monocytic cell line U937 is a frequently used model in studies on the
      cytotoxic effect of tumour necrosis factor (TNF). Two sublines of this cell line,
      termed U937(G) and U937(M), revealing different patterns of response to this
      cytokine, have been identified. The U937(G) cells, similarly to the cells
      obtained from ATCC, were resistant to the cytotoxic action of TNF in the absence
      of the protein-synthesis blocker cycloheximide (CHX). The U937(M) cells, however,
      were sensitive to the cytotoxic action of TNF both in the presence and absence of
      cycloheximide. Genetic analysis of the U937 sublines confirmed their common
      origin. The described U937 sublines may be useful models for analysis of the
      mechanisms of response to TNF. Additionally, our observation underscores the
      variability of the U937 cell line, which is described by most authors as a TNF
      sensitive line.

PMID- 11292321
TI  - Admission neopterin and interleukin 12 concentrations in identifying infections
      in adult cancer patients.
AB  - Differential diagnosis between infections and neoplastic fever is a common
      diagnostic problem. The utility of admission serum concentrations of neopterin
      and interleukin 12 (IL-12) was prospectively evaluated in this respect. The
      infection group (n=56) had a higher median neopterin value (12.8 nmol/l vs 4.0
      nmol/l, P<0.001) and neopterin-to-IL-12 ratio (1.74 vs 0.11, P<0.001) than the
      non-infection group (n=36); the median IL-12 values were higher in the latter
      group (10.6 pg/ml vs 71.6 pg/ml, P=0.007). According to the area under the
      operating characteristics curves (AUC), especially neopterin (0.90), but also the
      neopterin-to-IL-12 ratio (0.79), was good at identifying bacteremia. However, in
      differentiating infections in general from neoplastic fever (n=10), the neopterin
      to-IL-12 ratio was less powerful (0.64), though still better than neopterin
      (0.58) and clearly better than IL-12 (0.42). The present results show that the
      neopterin-to-IL-12 ratio, which reflects simultaneously both the ongoing
      infection and the tumour load, may have promising clinical implications for
      differential diagnosis between infections and neoplastic fever.

PMID- 11292322
TI  - DNA packaging and developmental intermediates of a broad host range Vibrio
      vulnificus bacteriophage 71A-6.
AB  - The structural intermediates in the capsid assembly and DNA packaging pathway of
      Vibrio vulnificus bacteriophage 71A-6, a rod-shaped double-stranded DNA
      podovirus, were isolated by ultracentrifugation and studied by electron
      microscopy, SDS-PAGE and pulsed-field gel electrophoretic analysis. Bacteriophage
      71A-6 synthesized rod-shaped capsids (mean length=200+/-8 nm; mean width=47+/-3
      nm n=50) during its development. Several host proteins that probably help in the
      assembly and maturation of the capsids were attached to these capsids as
      spherical structures. A capsid-DNA or DNA packaging complex that consisted of the
      mature capsids, DNA and a 42.5-kDa protein was also isolated. The size of the
      capsids increased in length and decreased in width (mean length=220+/-8 nm; mean
      width=45+/-3 nm n=50) either during or after the DNA packaging. The capsid
      fractions contained about 12 phage structural proteins and eight host proteins.
      At least three proteins were tentatively identified: a 38.5-kDa major capsid
      protein, a 35.2-kDa tail protein and 42.5-kDa packaging initiator or terminator
      protein. The size of the bacteriophage 71A-6 genome was determined to be 143.0-kb
      by pulsed-field gel electrophoresis. The total mass of all the mature phage
      proteins corresponded to only 14.0% of the coding capacity of phage genome.

PMID- 11292323
TI  - Rapid detection of the 22q11.2 deletion with quantitative real-time PCR.
AB  - We report the detection of 22q11.2 deletions using TaqMan(TM)PCR-based gene
      dosage analysis of patients previously diagnosed by fluorescent in situ
      hybridization (FISH). We performed quantitative PCR of the UFD1L gene from this
      region and showed a 99.7% statistical correlation between the two methods. The
      advantages of this method over FISH include: (i) rapidity; (ii) ease; (iii)
      relatively low cost and; (iv) the small quantities of DNA needed.

PMID- 11292325
TI  - Detection and quantitation of Aspergillus fumigatus in pure culture using
      polymerase chain reaction.
AB  - Research was conducted with laboratory cultures to establish a protocol for the
      rapid detection and quantitation of the thermophilic fungus, Aspergillus
      fumigatus, using genetic amplification. Oligonucleotide primers and a
      fluorescently labelled probe were designed for use with quantitative polymerase
      chain reaction (QPCR). Primers and probe were tested for selectivity, specificity
      and sensitivity of detection of the target organism using a fluorogenic nuclease
      assay and a sequence detector. The DNA extraction protocol consisted of enzymatic
      treatment and boiling of fungal spore suspensions followed by DNA concentration
      and purification. The primer set developed was specific for A. fumigatus and had
      a sensitivity of <20 template copies. These primers amplified all A. fumigatus
      isolates tested and did not amplify DNA extracted from other Aspergillus species
      or 15 other fungal genera. However, one A. fumigatus sample was initially
      negative after PCR amplification. Incorporation of an internal positive control
      in the PCR reaction demonstrated the presence of inhibitors in this and other
      samples. PCR inhibitors were removed by dilution or further purification of the
      DNA samples. This research resulted in a QPCR method for detection and
      quantitation of A. fumigatus and demonstrated the presence of PCR inhibitors in
      several A. fumigatus isolates.

PMID- 11292324
TI  - A novel 4-bp deletion creates a premature stop codon and dramatically decreases
      HEXB mRNA levels in a severe case of Sandhoff disease.
AB  - We present the molecular genetic analysis of an infantile-onset Sandhoff disease
      patient. Genomic DNA amplification, heteroduplex analysis, cloning and sequencing
      revealed a 4-bp deletion in exon 4 (497 DeltaAGTT). The result is a frameshift
      mutation that leads to a stop codon in exon 5. This mutation is associated with a
      dramatic decrease of HEXB mRNA levels.

PMID- 11292326
TI  - Minisatellite associated sequence amplification (MASA) of the hypervariable
      repeat marker 33.15 reveals a male specific band in humans.
AB  - The 16-nt (5' CACCTCTCCACCTGCC 3') consensus sequence of the hypervariable repeat
      marker 33.15 was used as primer to conduct minisatellite associated sequence
      amplification (MASA) of human genomic DNA. MASA detected a 513-bp Y chromosome
      specific band in males as well as a number of variable bands ranging from 260
      2700 bp in both the sexes. Overall polymorphism of the variable alleles was low
      with the band sharing probability of identity being 1.04x10(-4). Cloning and
      sequence analysis of the male specific band (GenBank accession no. AF134482)
      showed a high level (60-80%) of sequence homology with several human Y chromosome
      derived clones. Similar analysis of Indian rhinoceros (Rhinoceros unicornis)
      genomic DNA showed male specific isomorphic band though of different size. This
      assay may provide a useful method for the detection of Y chromosome related
      heterochromatic sequences in human and other vertebrates.

PMID- 11292327
TI  - Real-time genotyping of cytochrome P4501A1 A4889G and T6235C polymorphisms.
AB  - Single nucleotide polymorphisms, such as the cytochrome P450 1A1 (CYP1A1) A4889G
      and T6235C variants, have been reported to be associated with an increased cancer
      risk. In order to study their role in molecular-epidemiological studies, we
      developed a single-step procedure for genotyping these two CYP1A1 polymorphisms
      using real-time polymerase chain reaction (PCR) and subsequent melting curve
      analysis. Genotypes of 300 unrelated Caucasians, without prior history of cancer,
      were determined by real-time PCR and compared to genotypes obtained by
      restriction fragment length polymorphism PCR. In the population examined, the
      allele frequency of the CYP1A1 G allele at position 4889 was 0.042, and the
      frequency of the T allele at position 6235 was 0.10. Five percent of samples
      disagreed between methods. Sequence analysis of discordant samples revealed that
      the differences are likely attributed to incomplete digestion of amplicons by the
      RFLP method. These findings confirm the reliability and utility of real-time PCR
      as a method for large-scale genotyping.

PMID- 11292329
TI  - Progress towards a rapid polymerase chain reaction diagnostic test for the
      identification of Mycobacterium avium subsp. paratuberculosis in faeces.
AB  - Hybridization-capture polymerase chain reaction (HC-PCR), a nucleic acid sequence
      capture technique, was evaluated on faecal samples pooled from 50 sheep and
      individual faecal samples as a rapid diagnostic test for Mycobacterium avium
      subsp. paratuberculosis, the causative agent of Johne's disease. The status of
      each of the faecal samples was determined by radiometric culture. A simpler
      direct-PCR technique was evaluated on the same samples and was found to be more
      sensitive than HC-PCR. The lack of sensitivity of HC-PCR was neither due to
      location nor length of capture probe on IS 900 nor deterioration of the probe but
      was associated with inefficiencies in liquid phase hybridization and solid phase
      magnetic bead capture. Direct-PCR using primers from the 5' region of IS 900 was
      evaluated in a blind trial on 502 pooled faecal samples which were concurrently
      examined by culture. Twenty-one (64%) of the 33 culture positive pools were
      detected by direct PCR, representing 11 (79%) of the 14 farms with infected
      sheep. Direct-PCR was also more sensitive than immunomagnetic bead capture-PCR.
      Using individual faecal samples, 74% of culture positive samples were detected
      with direct-PCR compared to 44% with immunomagnetic bead capture-PCR. Direct-PCR
      from faeces can be used as a rapid means of screening pooled faecal samples for
      flock diagnosis of Johne's disease in sheep.

PMID- 11292328
TI  - Detection of minimal residual disease in peripheral blood prior to clinical
      relapse of childhood acute lymphoblastic leukaemia using PCR.
AB  - Submicroscopic evidence of persistent minimal residual disease (MRD) in first
      remission bone marrow samples from children with acute lymphoblastic leukaemia
      (ALL) indicates a high risk of clinical relapse. Since microscopic evidence of
      leukaemic lymphoblasts is often present in the peripheral blood in the weeks
      before clinical presentation at diagnosis or relapse, peripheral blood may be
      used instead of bone marrow to detect MRD in ALL patients. We examined a median
      of 0.165 microg (from 1.0-2.0x10(4)cells) genomic DNA from archived peripheral
      blood smears collected 8-16 months prior to clinical relapse in eight children
      with ALL for evidence of MRD. We used the polymerase chain reaction and primers
      designed to identify clonal antigen receptor gene rearrangements. Among the seven
      patients with bone marrow relapse, MRD was detected at a median of 1.2 months (0
      8 months) prior to clinical relapse, indicating that MRD in the peripheral blood
      may be a late event in the course of leukaemic relapse. A prospective MRD study
      in ALL patients analysing larger numbers of peripheral blood cells will be needed
      to evaluate the utility of peripheral blood over bone marrow for MRD testing in
      childhood ALL.

PMID- 11292330
TI  - Genetic variation of the methylenetetrahydrofolate reductase and cystathionine
      beta-synthase genes in Korean patients with coronary artery disease and a new
      polymorphism in intron 7.
AB  - We investigated polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and
      cystathionine beta-synthase (CBS) genes in Korean patients with coronary artery
      disease (CAD) and identified a new polymorphism (c-->t) in intron 7 of the CBS
      gene using the single-strand conformation polymorphism method. No significant
      differences were found in allele frequencies for either gene between the CAD and
      normal groups although the frequency of the so-called thermolabile MTHFR
      polymorphism, a proposed risk factor for CAD, was higher in Koreans than in other
      populations studied. The relatively low incidence of CAD in Korea suggests that
      this MTHFR polymorphism is not causative in this population.

PMID- 11292331
TI  - A G-to-A single nucleotide polymorphism in intron 2 of the human CACNA2D2 gene
      that maps at 3p21.3.

PMID- 11292332
TI  - Selective recognition of pyrimidine motif triplexes by a protein encoded by the
      bacterial transposon Tn7.
AB  - The bacterial transposon Tn7 is distinguished among mobile genetic elements by
      its targeting abilities. Recently, we reported that Tn7 is able to selectively
      insert adjacent to triple-helical DNA. The binding of TnsC, a Tn7-encoded
      protein, to the triplex DNA target leads to the specific transposition of Tn7
      adjacent to both inter- and intramolecular pyrimidine motif triplexes. Here, we
      further probe how Tn7 targets triplex DNA. We report that TnsC discriminates
      between different types of triplexes, showing binding preference for pyrimidine
      but not for purine motif intermolecular triplex DNA. The binding preferences of
      TnsC and the Tn7 insertion profiles were obtained using psoralenated, triplex-
      forming oligonucleotides annealed to plasmid DNAs. Although the presence of
      psoralen is not required for targeting nor is it alone able to attract TnsC, we
      show that the location of psoralen within the pyrimidine motif triplex does alter
      the position of Tn7 insertion relative to the triplex. Comparison between the
      triplex-targeting pathway and the highly site-specific targeting pathway mediated
      by the binding of the Tn7-encoded protein, TnsD, to the unique site attTn7,
      suggests that similar structural features within each target DNA are recognized
      by TnsC, leading to site-specific transposition. This work demonstrates that a
      prokaryotic protein involved in the targeting and regulation of Tn7
      translocation, TnsC, can selectively recognize pyrimidine motif triplexes.

PMID- 11292333
TI  - Pressure-induced formation of inactive triple-shelled rotavirus particles is
      associated with changes in the spike protein Vp4.
AB  - Rotaviruses are non-enveloped, triple-shelled particles that cause enteritis in
      animals and humans. The interactions among the different viral proteins located
      in the three concentric layers make the rotavirus particle an excellent model for
      physico-chemical and biological studies of viral assemblage. SA11-4S rotaviruses
      subjected to high pressure were inactivated by more than five log units. After
      pressure treatment, the particles were recovered with slight structural changes
      when compared to the control. Electron microscopy suggested subtle changes in the
      viral outer layer in some pressurised particles. Fluorescence spectroscopy showed
      that much more dramatic changes were produced by urea denaturation than by
      pressure. Based on the fluorescence spectrum, the genome resistance to
      ribonuclease, and the absence of changes in hydrodynamic properties, there was
      little or no disruption of the capsid under pressure. On the other hand,
      hemagglutination assays indicated that the main component affected by pressure
      was the spike protein VP4, thus accounting for changes in interaction with host
      cells and greatly reduced infectivity. The changes leading to inactivation did
      not cause removal of VP4 from the outer capsid, as verified by size-exclusion
      chromatography. Antibodies raised against pressurised material were as effective
      as antibodies raised against the intact virus, based on their neutralisation
      titre in plaque reduction assays, enzyme-linked immunosorbent assays and direct
      interaction with the particle, as measured by gel-filtration chromatography.
      Therefore, the new conformation of the pressurised particle did not result in
      loss of immunogenicity. We propose that pressure alters the receptor-binding
      protein VP4 by triggering changes similar to those produced when the virus
      interacts with target cells. As the changes in VP4 conformation caused by
      pressure occur prior to virus exposure to target cells, it leads to non
      infectious particles and may lead to the exposure of previously occult epitopes,
      important for vaccine development.

PMID- 11292334
TI  - Protein cofactor-dependent acquisition of novel catalytic activity by the RNase P
      ribonucleoprotein of E. coli.
AB  - Escherichia coli RNase P derivatives were evolved in vitro for DNA cleavage
      activity. Ribonucleoproteins sampled after ten generations of selection show a
      >400-fold increase in the first-order rate constant (k(cat)) on a DNA substrate,
      reflecting a significant improvement in the chemical cleavage step. This increase
      is offset by a reduction in substrate binding, as measured by K(M). We trace the
      catalytic enhancement to two ubiquitous A-->U sequence changes at positions 136
      and 333 in the M1 RNA component, positions that are phylogenetically conserved in
      the Eubacteria. Furthermore, although the mutations are located in different
      folding domains of the catalytic RNA, the first in the substrate binding domain,
      the second near the catalytic core, their effect on catalytic activity is
      significantly influenced by the presence of the C5 protein. The activity of the
      evolved ribonucleoproteins on both pre-4.5 S RNA and on an RNA oligo substrate
      remain at wild-type levels. In contrast, improved DNA cleavage activity is
      accompanied by a 500-fold decrease in pre-tRNA cleavage efficiency (k(cat)/K(M)).
      The presence of the C5 component does not buffer this tradeoff in catalytic
      activities, despite the in vivo role played by the C5 protein in enhancing the
      substrate versatility of RNase P. The change at position 136, located in the
      J11/12 single-stranded region, likely alters the geometry of the pre-tRNA-binding
      cleft and may provide a functional explanation for the observed tradeoff. These
      results thus shed light both on structure/function relations in E. coli RNase P
      and on the crucial role of proteins in enhancing the catalytic repertoire of RNA.

PMID- 11292335
TI  - Directionality of DNA replication fork movement strongly affects the generation
      of spontaneous mutations in Escherichia coli.
AB  - Using a pair of plasmids carrying the rpsL target sequence in different
      orientations to the replication origin, we analyzed a large number of forward
      mutations generated in wild-type and mismatch-repair deficient (MMR(-))
      Escherichia coli cells to assess the effects of directionality of replication
      fork movement on spontaneous mutagenesis and the generation of replication error.
      All classes of the mutations found in wild-type cells but not MMR(-) cells were
      strongly affected by the directionality of replication fork movement. It also
      appeared that the directionality of replication-fork movement governs the
      directionality of sequence substitution mutagenesis, which occurred in wild-type
      cells at a frequency comparable to base substitutions and single-base frameshift
      mutations. A very strong orientation-dependent hot-spot site for single-base
      frameshift mutations was discovered and demonstrated to be caused by the same
      process involved in sequence substitution mutagenesis. It is surprising that
      dnaE173, a potent mutator mutation specific for sequence substitution as well as
      single-base frameshift, did not enhance the frequency of the hot-spot frameshift
      mutation. Furthermore, the frequency of the hot-spot frameshift mutation was
      unchanged in the MMR(-) strain, whereas the mutHLS-dependent mismatch repair
      system efficiently suppressed the generation of single-base frameshift mutations.
      These results suggested that the hot-spot frameshift mutagenesis might be
      initiated at a particular location containing a DNA lesion, and thereby produce a
      premutagenic replication intermediate resistant to MMR. Significant numbers of
      spontaneous single-base frameshift mutations are probably caused by similar
      mechanisms.

PMID- 11292336
TI  - Rad54 protein stimulates heteroduplex DNA formation in the synaptic phase of DNA
      strand exchange via specific interactions with the presynaptic Rad51
      nucleoprotein filament.
AB  - RAD54 is an important member of the RAD52 group of genes that carry out
      recombinational repair of DNA damage in the yeast Saccharomyces cerevisiae. Rad54
      protein is a member of the Snf2/Swi2 protein family of DNA-dependent/stimulated
      ATPases, and its ATPase activity is crucial for Rad54 protein function. Rad54
      protein and Rad54-K341R, a mutant protein defective in the Walker A box ATP
      binding fold, were fused to glutathione-S-transferase (GST) and purified to near
      homogeneity. In vivo, GST-Rad54 protein carried out the functions required for
      methyl methanesulfonate sulfate (MMS), UV, and DSB repair. In vitro, GST-Rad54
      protein exhibited dsDNA-specific ATPase activity. Rad54 protein stimulated
      Rad51/Rpa-mediated DNA strand exchange by specifically increasing the kinetics of
      joint molecule formation. This stimulation was accompanied by a concurrent
      increase in the formation of heteroduplex DNA. Our results suggest that Rad54
      protein interacts specifically with established Rad51 nucleoprotein filaments
      before homology search on the duplex DNA and heteroduplex DNA formation. Rad54
      protein did not stimulate DNA strand exchange by increasing presynaptic complex
      formation. We conclude that Rad54 protein acts during the synaptic phase of DNA
      strand exchange and after the formation of presynaptic Rad51 protein-ssDNA
      filaments.

PMID- 11292337
TI  - The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode
      of inhibition.
AB  - Microcin B17 is a 3.1-kDa bactericidal peptide; the putative target of this
      antibiotic is DNA gyrase. Microcin B17 has no detectable effect on gyrase
      catalysed DNA supercoiling or relaxation activities in vitro and is unable to
      stabilise DNA cleavage in the absence of nucleotides. However, in the presence of
      ATP, or the non-hydrolysable analogue 5'-adenylyl beta,gamma-imidodiphosphate,
      microcin B17 stabilises a gyrase-dependent DNA cleavage complex in a manner
      reminiscent of quinolones, Ca(2+), or the bacterial toxin CcdB. The pattern of
      DNA cleavage produced by gyrase in the presence of microcin B17 is different from
      that produced by quinolones and more closely resembles Ca(2+)-mediated cleavage.
      Several gyrase mutants, including well-known quinolone-resistant mutants, are
      cross resistant to microcin-induced DNA cleavage. We suggest that microcin exerts
      its effects through a mechanism that has similarities to those of both the
      bacterial toxin CcdB and the quinolone antibacterial agents.

PMID- 11292338
TI  - DNA double-strand breaks associated with replication forks are predominantly
      repaired by homologous recombination involving an exchange mechanism in mammalian
      cells.
AB  - DNA double-strand breaks (DSB) represent a major disruption in the integrity of
      the genome. DSB can be generated when a replication fork encounters a DNA lesion.
      Recombinational repair is known to resolve such replication fork-associated DSB,
      but the molecular mechanism of this repair process is poorly understood in
      mammalian cells. In the present study, we investigated the molecular mechanism by
      which recombination resolves camptothecin (CPT)-induced DSB at DNA replication
      forks. The frequency of homologous recombination (HR) was measured using V79/SPD8
      cells which contain a duplication in the endogenous hprt gene that is resolved by
      HR. We demonstrate that DSB associated with replication forks induce HR at the
      hprt gene in early S phase. Further analysis revealed that these HR events
      involve an exchange mechanism. Both the irs1SF and V3-3 cell lines, which are
      deficient in HR and non-homologous end joining (NHEJ), respectively, were found
      to be more sensitive than wild-type cells to DSB associated with replication
      forks. The irs1SF cell line was more sensitive in this respect than V3-3 cells,
      an observation consistent with the hypothesis that DSB associated with
      replication forks are repaired primarily by HR. The frequency of formation of DSB
      associated with replication forks was not affected in HR and NHEJ deficient
      cells, indicating that the loss of repair, rather than the formation of DSB
      associated with replication forks is responsible for the increased sensitivity of
      the mutant strains. We propose that the presence of DSB associated with
      replication forks rapidly induces HR via an exchange mechanism and that HR plays
      a more prominent role in the repair of such DSB than does NHEJ.

PMID- 11292339
TI  - Supporting the structural basis of prion strains: induction and identification of
      [PSI] variants.
AB  - The [PSI] genetic element, which enhances the nonsense suppression efficiency in
      the yeast Saccharomyces cerevisiae, is thought to be amyloid-like aggregates of
      the Sup35 protein, and to self-propagate by a prion-like mechanism. Analogous to
      strains of the mammalian prion, variants of [PSI], with different nonsense
      suppression efficiencies and mitotic stabilities, can be isolated from the same
      yeast genetic background. In the framework of the "protein-only" hypothesis,
      variants of prion are assumed to be distinct conformers of the same prion
      polypeptide. This study aims to provide further support for the structural basis
      of [PSI] variation. Three variants of [PSI] were induced and distinguished by a
      panel of 11 single point mutations of the Sup35 protein. The variant phenotypes
      are intrinsically associated with [PSI] elements, presumably structurally
      different amyloids, rather than produced from variations in the genetic
      background. Differential incorporation to [PSI] variants of a Sup35 point
      mutation as well as N and C-terminally truncated Sup35 fragments is further
      demonstrated in vivo, suggesting that distinct patches of amino acid residues are
      involved in the assembly of [PSI] variants. These results establish a method for
      [PSI] variant-typing and indicate that heritable variations of amyloid structures
      can be derived from the same polypeptide.

PMID- 11292340
TI  - A novel mutation in the neurofibromatosis type 1 (NF1) gene promotes skipping of
      two exons by preventing exon definition.
AB  - Using a protein truncation assay, we have identified a new mutation in the
      neurofibromatosis type 1 (NF1) gene that causes a severe defect in NF1 pre-mRNA
      splicing. The mutation, which consists of a G to A transition at position +1 of
      the 5' splice site of exon 12a, is associated with the loss of both exons 11 and
      12a in the NF1 mRNA. Through the use of in vivo and in vitro splicing assays, we
      show that the mutation inactivates the 5' splice site of exon 12a, and prevents
      the definition of exon 12a, a process that is normally required to stimulate the
      weak 3' splice site of exon 12a. Because the 5' splice site mutation weakens the
      interaction of splicing factors with the 3' splice site of exon 12a, we propose
      that exon 11/exon 12a splicing is also compromised, leading to the exclusion of
      both exons 11 and 12a. Our results provide in vivo support for the importance of
      the exon definition model during NF1 splicing, and suggest that the NF1 region
      containing exons 11 and 12a plays an important role in the activity of
      neurofibromin.

PMID- 11292341
TI  - Regulatory potential, phyletic distribution and evolution of ancient,
      intracellular small-molecule-binding domains.
AB  - Central cellular functions such as metabolism, solute transport and signal
      transduction are regulated, in part, via binding of small molecules by
      specialized domains. Using sensitive methods for sequence profile analysis and
      protein structure comparison, we exhaustively surveyed the protein sets from
      completely sequenced genomes for all occurrences of 21 intracellular small
      molecule-binding domains (SMBDs) that are represented in at least two of the
      three major divisions of life (bacteria, archaea and eukaryotes). These included
      previously characterized domains such as PAS, GAF, ACT and ferredoxins, as well
      as three newly predicted SMBDs, namely the 4-vinyl reductase (4VR) domain, the
      NIFX domain and the 3-histidines (3H) domain. Although there are only a limited
      number of different superfamilies of these ancient SMBDs, they are present in
      numerous distinct proteins combined with various enzymatic, transport and signal
      transducing domains. Most of the SMBDs show considerable evolutionary mobility
      and are involved in the generation of many lineage-specific domain architectures.
      Frequent re-invention of analogous architectures involving functionally related,
      but not homologous, domains was detected, such as, fusion of different SMBDs to
      several types of DNA-binding domains to form diverse transcription regulators in
      prokaryotes and eukaryotes. This is suggestive of similar selective forces
      affecting the diverse SMBDs and resulting in the formation of multidomain
      proteins that fit a limited number of functional stereotypes. Using the "guilt by
      association approach", the identification of SMBDs allowed prediction of
      functions and mode of regulation for a variety of previously uncharacterized
      proteins.

PMID- 11292342
TI  - The C-terminal half of the colicin A pore-forming domain is active in vivo and in
      vitro.
AB  - The pore-forming domain of colicin A (pfColA) fused to a prokaryotic signal
      peptide (sp-pfColA) is transported across and inserts into the inner membrane of
      Escherichia coli from the periplasmic side and forms a functional channel. The
      soluble structure of pfColA consists of a ten-helix bundle containing a
      hydrophobic helical hairpin. Here, we generated a series of mutants in which an
      increasing number of sp-pfColA alpha-helices was deleted. These peptides were
      tested for their ability to form ion channels in vivo and in vitro. We found that
      the shortest sp-pfColA mutant protein that killed Escherichia coli was composed
      of the five last alpha-helices of sp-pfColA, whereas the shortest peptide that
      formed a channel in planar lipid bilayer membranes similar to that of intact
      pfColA was the protein composed of the last six alpha-helices. The peptide
      composed of the last five alpha-helices of pfColA generated a voltage-independent
      conductance in planar lipid bilayer with properties very different from that of
      intact pfColA. Thus, helices 1 to 4 are unnecessary for channel formation, while
      helix 5, or some part of it, is important but not absolutely necessary. Voltage
      dependence of colicin is evidently controlled by the first four alpha-helices of
      pfColA.

PMID- 11292343
TI  - High affinity T cell receptors from yeast display libraries block T cell
      activation by superantigens.
AB  - The alphabeta T cell receptor (TCR) can be triggered by a class of ligands called
      superantigens. Enterotoxins secreted by bacteria act as superantigens by
      simultaneously binding to an MHC class II molecule on an antigen- presenting cell
      and to a TCR beta-chain, thereby causing activation of the T cell. The cross
      reactivity of enterotoxins with different Vbeta regions can lead to stimulation
      of a large fraction of T cells. To understand the molecular details of TCR
      enterotoxin interactions and to generate potential antagonists of these serious
      hyperimmune reactions, we engineered soluble TCR mutants with improved affinity
      for staphylococcal enterotoxin C3 (SEC3). A library of randomly mutated, single
      chain TCRs (Vbeta-linker-Valpha) were expressed as fusions to the Aga2p protein
      on the surface of yeast cells. Mutants were selected by flow cytometric cell
      sorting with a fluorescent-labeled SEC3. Various mutations were identified,
      primarily in Vbeta residues that are located at the TCR:SEC3 interface. The
      combined mutations created a remodeled SEC3-binding surface and yielded a Vbeta
      domain with an affinity that was increased by 1000-fold (K(D)=7 nM). A soluble
      form of this Vbeta mutant was a potent inhibitor of SEC3-mediated T cell
      activity, suggesting that these engineered proteins may be useful as antagonists.

PMID- 11292344
TI  - Antibodies to cytoplasmic dynein heavy chain map the surface and inhibit
      motility.
AB  - Polyclonal antibodies have been raised against four 16 residue peptides with
      sequences taken from the C-terminal quarter of the human cytoplasmic dynein heavy
      chain. The sites are downstream from a known microtubule-binding domain
      associated with the "stalk" that protrudes from the motor domain. The antisera
      were assayed using bacterially expressed proteins with amino acid sequences taken
      from the human cytoplasmic dynein heavy chain. Every antiserum reacted
      specifically with the appropriate expressed protein and with pig brain
      cytoplasmic dynein, whether the protein molecules were denatured on Western blots
      or were in a folded state. But, whereas three of the four antisera recognized
      freshly purified cytoplasmic dynein, the fourth reacted only with dynein that had
      been allowed to denature a little. After affinity purification against the
      expressed domains, whole IgG molecules and Fab fragments were assayed for their
      effect on dynein activity in in vitro microtubule-sliding assays. Of the three
      anti-peptides that reacted with fresh dynein, one inhibited motility but the
      others did not. The way these peptides are exposed on the surface is compatible
      with a model whereby the dynein motor domain is constructed from a ring of AAA
      protein modules, with the C-terminal module positioned on the surface that
      interacts with microtubules. We have tentatively identified an additional AAA
      module in the dynein heavy chain sequence, which would be consistent with a
      heptameric ring.

PMID- 11292345
TI  - Selection of ligands by panning of domain libraries displayed on phage lambda
      reveals new potential partners of synaptojanin 1.
AB  - One of the goals of functional genomics is the description of reliable and
      complete protein interaction networks. To facilitate ligand discovery from
      complex protein mixtures, we have developed an improved approach that is affected
      by a negligible fraction of false positives. We have combined a novel technique
      based on the display of cDNA libraries on the capsid of bacteriophage lambda and
      an efficient plaque assay to reveal phage displaying ligands that are enriched
      after only a couple of affinity purification steps. We show that the lambda
      display system has a unique ability to display, at high density, proteins ranging
      in size from a few to at least 300 amino acid residues. This characteristic
      permits attenuation of the size bias in the selection procedure and, at the same
      time, offers a sensitive plaque assay that permits us to do away with the ligand
      background without unduly increasing the number of selection cycles. By using a
      proline-rich fragment of the synaptojanin 1 protein as a bait, we have
      identified, in a brain cDNA display library, seven ligands all containing either
      SH3 or WW domains. Four of these correspond to proteins that have already been
      validated as physiological partners, while the remaining three are new partners,
      whose physiological relevance remains to be established. Two different proline
      rich regions of the p21-activated protein kinase 1 (Pak1) and WAVE/SCAR2 protein
      retrieve from the library different proteins containing SH3 or WW domains.

PMID- 11292346
TI  - Direct localization by cryo-electron microscopy of secondary structural elements
      in Escherichia coli 23 S rRNA which differ from the corresponding regions in
      Haloarcula marismortui.
AB  - Insertions were introduced by a two-step mutagenesis procedure into each of five
      double-helical regions of Escherichia coli 23 S rRNA, so as to extend the helix
      concerned by 17 bp. The helices chosen were at sites within the 23 S molecule
      (h9, h25, h45, h63 and h98) where significant length variations between different
      species are known to occur. At each of these positions, with the exception of
      h45, there are also significant differences between the 23 S rRNAs of E. coli and
      Haloarcula marismortui. Plasmids carrying the insertions were introduced into an
      E. coli strain lacking all seven rrn operons. In four of the five cases the cells
      were viable and 50 S subunits could be isolated; only the insertion in h63 was
      lethal. The modified subunits were examined by cryo-electron microscopy (cryo
      EM), with a view to locating extra electron density corresponding to the
      insertion elements. The results were compared both with the recently determined
      atomic structure of H. marismortui 23 S rRNA in the 50 S subunit, and with
      previous 23 S rRNA modelling studies based on cryo-EM reconstructions of E. coli
      ribosomes. The insertion element in h45 was located by cryo-EM at a position
      corresponding precisely to that of the equivalent helix in H. marismortui. The
      insertion in h98 (which is entirely absent in H. marismortui) was similarly
      located at a position corresponding precisely to that predicted from the E. coli
      modelling studies. In the region of h9, the difference between the E. coli and H.
      marismortui secondary structures is ambiguous, and the extra electron density
      corresponding to the insertion was seen at a location intermediate between the
      position of the nearest helix in the atomic structure and that in the modelled
      structure. In the case of h25 (which is about 50 nucleotides longer in H.
      marismortui), no clear extra cryo-EM density corresponding to the insertion could
      be observed.

PMID- 11292347
TI  - Crystal structure of the MJ0490 gene product of the hyperthermophilic
      archaebacterium Methanococcus jannaschii, a novel member of the lactate/malate
      family of dehydrogenases.
AB  - The MJ0490 gene, one of the only two genes of Methanococcus jannaschii showing
      sequence similarity to the lactate/malate family of dehydrogenases, was
      classified initially as coding for a putative l-lactate dehydrogenase (LDH). It
      has been re-classified as a malate dehydrogenase (MDH) gene, because it shows
      significant sequence similarity to MT0188, MDH II from Methanobacterium
      thermoautotrophicum strain DeltaH. The three-dimensional structure of its gene
      product has been determined in two crystal forms: a "dimeric" structure in the
      orthorhombic crystal at 1.9 A resolution and a "tetrameric" structure in the
      tetragonal crystal at 2.8 A. These structures share a similar subunit fold with
      other LDHs and MDHs. The tetrameric structure resembles typical tetrameric LDHs.
      The dimeric structure is equivalent to the P-dimer of tetrameric LDHs, unlike
      dimeric MDHs, which correspond to the Q-dimer. The structure reveals that the
      cofactor NADP(H) is bound at the active site, despite the fact that it was not
      intentionally added during protein purification and crystallization. The
      preference of NADP(H) over NAD(H) has been supported by activity assays. The
      cofactor preference is explained by the presence of a glycine residue in the
      cofactor binding pocket (Gly33), which replaces a conserved aspartate (or
      glutamate) residue in other NAD-dependent LDHs or MDHs. Preference for NADP(H) is
      contributed by hydrogen bonds between the oxygen atoms of the monophosphate group
      and the ribose sugar of adenosine in NADP(H) and the side-chains of Ser9, Arg34,
      His36, and Ser37. The MDH activity of MJ0490 is made possible by Arg86, which is
      conserved in MDHs but not in LDHs. The enzymatic assay showed that the MJ0490
      protein possesses the fructose-1,6-bisphosphate-activated LDH activity
      (reduction). Thus the MJ0490 gene product appears to be a novel member of the
      lactate/malate dehydrogenase family, displaying an LDH scaffold and exhibiting a
      relaxed substrate and cofactor specificities in NADP(H) and NAD(H)-dependent
      malate and lactate dehydrogenase reactions.

PMID- 11292348
TI  - Structure and function of a novel purine specific nucleoside hydrolase from
      Trypanosoma vivax.
AB  - The purine salvage pathway of parasitic protozoa is currently considered as a
      target for drug development because these organisms cannot synthesize purines de
      novo. Insight into the structure and mechanism of the involved enzymes can aid in
      the development of potent inhibitors, leading to new curative drugs. Nucleoside
      hydrolases are key enzymes in the purine salvage pathway of Trypanosomatidae, and
      they are especially attractive because they have no equivalent in mammalian
      cells. We cloned, expressed and purified a nucleoside hydrolase from Trypanosoma
      vivax. The substrate activity profile establishes the enzyme to be a member of
      the inosine-adenosine-guanosine-preferring nucleoside hydrolases (IAG-NH). We
      solved the crystal structure of the enzyme at 1.6 A resolution using MAD
      techniques. The complex of the enzyme with the substrate analogue 3-deaza
      adenosine is presented. These are the first structures of an IAG-NH reported in
      the literature. The T. vivax IAG-NH is a homodimer, with each subunit consisting
      of ten beta-strands, 12 alpha-helices and three small 3(10)-helices. Six of the
      eight strands of the central beta-sheet form a motif resembling the Rossmann
      fold. Superposition of the active sites of this IAG-NH and the inosine-uridine
      preferring nucleoside hydrolase (IU-NH) of Crithidia fasciculata shows the
      molecular basis of the different substrate specificity distinguishing these two
      classes of nucleoside hydrolases. An "aromatic stacking network" in the active
      site of the IAG-NH, absent from the IU-NH, imposes the purine specificity. Asp10
      is the proposed general base in the reaction mechanism, abstracting a proton from
      a nucleophilic water molecule. Asp40 (replaced by Asn39 in the IU-NH) is
      positioned appropriately to act as a general acid and to protonate the purine
      leaving group. The second general acid, needed for full enzymatic activity, is
      probably part of a flexible loop located in the vicinity of the active site.

PMID- 11292349
TI  - Inhibitory and blocking monoclonal antibody epitopes on merozoite surface protein
      1 of the malaria parasite Plasmodium falciparum.
AB  - Merozoite surface protein 1 (MSP-1) is a precursor to major antigens on the
      surface of Plasmodium spp. merozoites, which are involved in erythrocyte binding
      and invasion. MSP-1 is initially processed into smaller fragments; and at the
      time of erythrocyte invasion one of these of 42 kDa (MSP-1(42)) is subjected to a
      second processing, producing 33 kDa and 19 kDa fragments (MSP-1(33) and MSP
      1(19)). Certain MSP-1-specific monoclonal antibodies (mAbs) react with
      conformational epitopes contained within the two epidermal growth factor domains
      that comprise MSP-1(19), and are classified as either inhibitory (inhibit
      processing of MSP-1(42) and erythrocyte invasion), blocking (block the binding
      and function of the inhibitory mAb), or neutral (neither inhibitory nor
      blocking). We have mapped the epitopes for inhibitory mAbs 12.8 and 12.10, and
      blocking mAbs such as 1E1 and 7.5 by using site-directed mutagenesis to change
      specific amino acid residues in MSP-1(19) and abolish antibody binding, and by
      using PEPSCAN to measure the reaction of the antibodies with every octapeptide
      within MSP-1(42). Twenty-six individual amino acid residue changes were made and
      the effect of each on the binding of mAbs was assessed by Western blotting and
      BIAcore analysis. Individual changes had either no effect, or reduced, or
      completely abolished the binding of individual mAbs. No two antibodies had an
      identical pattern of reactivity with the modified proteins. Using PEPSCAN each
      mAb reacted with a number of octapeptides, most of which were derived from within
      the first epidermal growth factor domain, although 1E1 also reacted with peptides
      spanning the processing site. When the single amino acid changes and the reactive
      peptides were mapped onto the three-dimensional structure of MSP-1(19), it was
      apparent that the epitopes for the mAbs could be defined more fully by using a
      combination of both mutagenesis and PEPSCAN than by either method alone, and
      differences in the fine specificity of binding for all the different antibodies
      could be distinguished. The incorporation of several specific amino acid changes
      enabled the design of proteins that bound inhibitory but not blocking antibodies.
      These may be suitable for the development of MSP-1-based vaccines against
      malaria.

PMID- 11292350
TI  - Structure, function, and dynamics of the dimerization and DNA-binding domain of
      oncogenic transcription factor v-Myc.
AB  - The protein product (c-Myc) of the protooncogene c-myc is a transcriptional
      regulator playing a key role in cellular growth, differentiation, and apoptosis.
      Deregulated myc genes, like the transduced retroviral v-myc allele, are oncogenic
      and cause cell transformation. The C-terminal bHLHZip domain of v-Myc,
      encompassing protein dimerization (helix-loop-helix, leucine zipper) and DNA
      contact (basic region) surfaces, was expressed in bacteria as a highly soluble
      p15(v-myc )recombinant protein. Dissociation constants (K(d)) for the heterodimer
      formed with the recombinant bHLHZip domain of the Myc binding partner Max
      (p14(max)) and for the Myc-Max-DNA complex were estimated using circular
      dichroism (CD) spectroscopy and quantitative electrophoretic mobility shift assay
      (EMSA). Multi-dimensional NMR spectroscopy was used to characterize the solution
      structural and dynamic properties of the v-Myc bHLHZip domain. Significant
      secondary chemical shifts indicate the presence of two separated alpha-helical
      regions. The C-terminal leucine zipper region forms a compact alpha-helix, while
      the N-terminal basic region exhibits conformational averaging with substantial
      alpha-helical content. Both helices lack stabilizing tertiary side-chain
      interactions and represent exceptional examples for loosely coupled secondary
      structural segments in a native protein. These results and CD thermal
      denaturation data indicate a monomeric state of the v-Myc bHLHZip domain. The
      (15)N relaxation data revealed backbone mobilities which corroborate the
      existence of a partially folded state, and suggest a "beads-on-a-string" motional
      behaviour of the v-Myc bHLHZip domain in solution. The preformation of alpha
      helical regions was confirmed by CD thermal denaturation studies, and
      quantification of the entropy changes caused by the hydrophobic effect and the
      reduction of conformational entropy upon protein dimerization. The restricted
      conformational space of the v-Myc bHLHZip domain reduces the entropy penalty
      associated with heterodimerization and allows rapid and accurate recognition by
      the authentic Myc binding partner Max.

PMID- 11292351
TI  - The beta-beta-alpha fold: explorations in sequence space.
AB  - The computational redesign of the second zinc finger of Zif268 to produce a 28
      residue peptide (FSD-1) that assumes a betabetaalpha fold without metal binding
      was recently reported. In order to explore the tolerance of this metal-free fold
      towards sequence variability, six additional peptides resulting from the ORBIT
      computational protein design process were synthesized and characterized. The
      experimental stabilities of five of these peptides are strongly correlated with
      the energies calculated by ORBIT. However, when a peptide with a mutation in the
      beta-turn is examined, the calculated stability does not accurately predict the
      experimentally determined stability. The NMR solution structure of a peptide
      incorporating this mutation (FSD-EY) reveals that the register between the beta
      strands is different from the model structure used to select and score the
      sequences. FSD-EY has a type I' turn instead of the target EbaaagbE turn
      (rubredoxin knuckle). Two additional peptides that have improved side-chain to
      backbone hydrogen bonding and turn propensity for the target turn were
      characterized. Both are of stability comparable to that of FSD-1. These results
      demonstrate the robustness of the ORBIT protein design methods and underscore the
      need for continued improvements in negative design.

PMID- 11292352
TI  - Van der Waals locks: loop-n-lock structure of globular proteins.
AB  - In a globular protein the polypeptide chain returns to itself many times, making
      numerous chain-to-chain contacts. The stability of these contacts is maintained
      primarily by van der Waals interactions. In this work we isolated and analysed
      van der Waals contacts that stabilise spatial structures of nine major folds. We
      suggest a specific way to identify the tightest contacts of prime importance for
      the stability of a given crystallized protein and introduce the notion of the van
      der Waals lock. The loops closed by the van der Waals interactions provide a
      basically novel view of protein globule organization: the loop-n-lock structure.
      This opens a new perspective in understanding protein folding as well: the
      consecutive looping of the polypeptide chain and the locking of the loop ends by
      tight van der Waals interactions.

PMID- 11292353
TI  - Socket: a program for identifying and analysing coiled-coil motifs within protein
      structures.
AB  - The coiled coil is arguably the simplest protein-structure motif and probably the
      most ubiquitous facilitator of protein-protein interactions. Coiled coils
      comprise two or more alpha-helices that wind around each other to form
      "supercoils". The hallmark of most coiled coils is a regular sequence pattern
      known as the heptad repeat. Despite this apparent simplicity and relatedness at
      the sequence level, coiled coils display a considerable degree of structural
      diversity: the helices may be arranged parallel or anti-parallel and may form a
      variety of oligomer states. To aid studies of coiled coils, we developed SOCKET,
      a computer program to identify these motifs automatically in protein structures.
      We used SOCKET to gather a set of unambiguous coiled-coil structures from the
      RCSB Protein Data Bank. Rather than searching for sequence features, the
      algorithm recognises the characteristic knobs-into-holes side-chain packing of
      coiled coils; this proved to be straightforward to implement and was able to
      distinguish coiled coils from the great majority of helix-helix packing
      arrangements observed in globular domains. SOCKET unambiguously defines coiled
      coil helix boundaries, oligomerisation states and helix orientations, and also
      assigns heptad registers. Structures retrieved from the Protein Data Bank
      included parallel and anti-parallel variants of two, three and four-stranded
      coiled coils, one example of a parallel pentamer and a small number of structures
      that extend the classical description of a coiled coil. We anticipate that our
      structural database and the associated sequence data that we have gathered will
      be of use in identifying principles for coiled-coil assembly, prediction and
      design. To illustrate this we give examples of sequence and structural analyses
      of the structures that are possible using the new data bases, and we present
      amino acid profiles for the heptad repeats of different motifs.

PMID- 11292354
TI  - A novel serine protease inhibition motif involving a multi-centered short
      hydrogen bonding network at the active site.
AB  - We describe a new serine protease inhibition motif in which binding is mediated
      by a cluster of very short hydrogen bonds (<2.3 A) at the active site. This
      protease-inhibitor binding paradigm is observed at high resolution in a large set
      of crystal structures of trypsin, thrombin, and urokinase-type plasminogen
      activator (uPA) bound with a series of small molecule inhibitors (2-(2
      phenol)indoles and 2-(2-phenol)benzimidazoles). In each complex there are eight
      enzyme-inhibitor or enzyme-water-inhibitor hydrogen bonds at the active site,
      three of which are very short. These short hydrogen bonds connect a triangle of
      oxygen atoms comprising O(gamma)(Ser195), a water molecule co-bound in the
      oxyanion hole (H(2)O(oxy)), and the phenolate oxygen atom of the inhibitor (O6').
      Two of the other hydrogen bonds between the inhibitor and active site of the
      trypsin and uPA complexes become short in the thrombin counterparts, extending
      the three-centered short hydrogen-bonding array into a tetrahedral array of atoms
      (three oxygen and one nitrogen) involved in short hydrogen bonds. In the uPA
      complexes, the extensive hydrogen-bonding interactions at the active site prevent
      the inhibitor S1 amidine from forming direct hydrogen bonds with Asp189 because
      the S1 site is deeper in uPA than in trypsin or thrombin. Ionization equilibria
      at the active site associated with inhibitor binding are probed through
      determination and comparison of structures over a wide range of pH (3.5 to 11.4)
      of thrombin complexes and of trypsin complexes in three different crystal forms.
      The high-pH trypsin-inhibitor structures suggest that His57 is protonated at pH
      values as high as 9.5. The pH-dependent inhibition of trypsin, thrombin, uPA and
      factor Xa by 2-(2-phenol)benzimidazole analogs in which the pK(a) of the phenol
      group is modulated is shown to be consistent with a binding process involving
      ionization of both the inhibitor and the enzyme. These data further suggest that
      the pK(a) of His57 of each protease in the unbound state in solution is about the
      same, approximately 6.8. By comparing inhibition constants (K(i) values),
      inhibitor solubilities, inhibitor conformational energies and corresponding
      structures of short and normal hydrogen bond-mediated complexes, we have
      estimated the contribution of the short hydrogen bond networks to inhibitor
      affinity ( approximately 1.7 kcal/mol). The structures and K(i) values associated
      with the short hydrogen-bonding motif are compared with those corresponding to an
      alternate, Zn(2+)-mediated inhibition motif at the active site. Structural
      differences among apo-enzymes, enzyme-inhibitor and enzyme-inhibitor-Zn(2+)
      complexes are discussed in the context of affinity determinants, selectivity
      development, and structure-based inhibitor design.

PMID- 11292355
TI  - Three-dimensional cluster analysis identifies interfaces and functional residue
      clusters in proteins.
AB  - Three-dimensional cluster analysis offers a method for the prediction of
      functional residue clusters in proteins. This method requires a representative
      structure and a multiple sequence alignment as input data. Individual residues
      are represented in terms of regional alignments that reflect both their
      structural environment and their evolutionary variation, as defined by the
      alignment of homologous sequences. From the overall (global) and the residue
      specific (regional) alignments, we calculate the global and regional similarity
      matrices, containing scores for all pairwise sequence comparisons in the
      respective alignments. Comparing the matrices yields two scores for each residue.
      The regional conservation score (C(R)(x)) defines the conservation of each
      residue x and its neighbors in 3D space relative to the protein as a whole. The
      similarity deviation score (S(x)) detects residue clusters with sequence
      similarities that deviate from the similarities suggested by the full-length
      sequences. We evaluated 3D cluster analysis on a set of 35 families of proteins
      with available cocrystal structures, showing small ligand interfaces, nucleic
      acid interfaces and two types of protein-protein interfaces (transient and
      stable). We present two examples in detail: fructose-1,6-bisphosphate aldolase
      and the mitogen-activated protein kinase ERK2. We found that the regional
      conservation score (C(R)(x)) identifies functional residue clusters better than a
      scoring scheme that does not take 3D information into account. C(R)(x) is
      particularly useful for the prediction of poorly conserved, transient protein
      protein interfaces. Many of the proteins studied contained residue clusters with
      elevated similarity deviation scores. These residue clusters correlate with
      specificity-conferring regions: 3D cluster analysis therefore represents an
      easily applied method for the prediction of functionally relevant spatial
      clusters of residues in proteins.

PMID- 11292356
TI  - Four loops of the catalytic domain of factor viia mediate the effect of the first
      EGF-like domain substitution on factor viia catalytic activity.
AB  - The presence of tissue factor is essential for factor VIIa (FVIIa) to reach its
      full catalytic potential. The previous work in this laboratory demonstrated that
      substitution of the EGF1 domain of factor VIIa with that of factor IX
      (FVII((IXegf1))a) results in a substantial decrease in TF-binding affinity and
      catalytic activity. Supporting simulations of the solution structures of Ca(2+)
      bound factor VIIa and FVII((IXegf1))a with tissue factor are provided. Mutants
      are generated, based on the simulation model, to study the effect of EGF1
      substitution on catalytic activity. The simulations show larger Gla-EGF1 and EGF1
      EGF2 inter-domain motions for FVII((IXegf1))a than for factor VIIa. The catalytic
      domain of the chimeric factor VIIa has been disturbed and several surface loops
      in the catalytic domain of FVII((IXegf1))a (Loop 170s (170-182), Loop 1 (185-188)
      and Loop 2 (221A-225)) manifest larger position fluctuations than wild-type. The
      position of Loop 140s (142-152) of FVII((IXegf1))a, near the N terminus insertion
      site of the catalytic domain, shifts relative to factor VIIa, resulting in a
      slight alteration of the active site. The results suggest that these four loops
      mediate the effect of the EGF1 domain substitution on the S1 site and catalytic
      residues. To test the model, we prepared mutations of these surface loops,
      including four FVII mutants, D186A, K188A, L144A and R147A, a FVII mutant with
      multiple mutations (MM3: L144A+R147A+D186A) and a FVII mutant with Loop 170s
      partially deleted, Loop 170s(del). The catalytic activities towards a small
      peptidyl substrate decreased 2.4, 4.5 and 9-fold for Loop 170s(del)a (a,
      activated), L144Aa and D186Aa, respectively, while MM3a lost almost all catalytic
      activity. The combined results of the simulations and mutants provide insight
      into the mechanism by which tissue factor enhances factor VIIa catalytic
      activity.

PMID- 11292357
TI  - Nitric oxide-dependent nitrosation of cellular CoA: a proposal for tissue
      responses.

PMID- 11292358
TI  - Nitric oxide and atherosclerosis.
AB  - Endothelial dysfunction has been shown in a wide range of vascular disorders
      including atherosclerosis and related diseases. Here, we examine and address the
      complex relationship among nitric oxide (NO)-mediated pathways and atherogenesis.
      In view of the numerous pathophysiological actions of NO, abnormalities could
      potentially occur at many sites: (a) impairment of membrane receptors in the
      arterial wall that interact with agonists or physiological stimuli capable of
      generating NO; (b) reduced concentrations or impaired utilization of l-arginine;
      (c) reduction in concentration or activity both of inducible and endothelial NO
      synthase; (d) impaired release of NO from the atherosclerotic damaged
      endothelium; (e) impaired NO diffusion from endothelium to vascular smooth muscle
      cells followed by decreased sensitivity to its vasodilator action; (f) local
      enhanced degradation of NO by increased generation of free radicals and/or
      oxidation-sensitive mechanisms; and (g) impaired interaction of NO with guanylate
      cyclase and consequent limitation of cyclic GMP production. Therefore, one target
      for new drugs should be the preservation or restoration of NO-mediated signaling
      pathways in arteries. Such novel therapeutic strategies may include
      administration of l-arginine/antioxidants and gene-transfer approaches.

PMID- 11292359
TI  - Nitric oxide inhibition of renal vasoconstrictor responses to sympathetic
      cotransmitters in the pig in vivo.
AB  - The object of the present study was to investigate the involvement of nitric
      oxide (NO) in the regulation of renal vasoconstrictor responses to sympathetic
      nerve activation, and each of the known sympathetic cotransmitters separately, in
      the pig in vivo. Renal vasoconstrictor responses were elicited by sympathetic
      nerve stimulation, the alpha(1)-adrenoceptor agonist phenylephrine (10 nmol kg(
      1), injected iv), neuropeptide Y (NPY, 120 pmol kg(-1), iv) acting on the NPY
      Y(1) receptor, and the stable ATP-analogue alpha,beta-methylene ATP (mATP, 10
      nmol kg(-1)) presumably acting on the P2X(1) purinoceptor. Infusion of the NO
      donor sodium nitroprusside, at a dose (0.1 mg kg(-1) h(-1), iv) that elevated
      renal blood flow (by 14 +/- 7%) and lowered mean arterial pressure (by 30 +/-
      5%), inhibited renal vasoconstrictor responses to sympathetic nerve stimulation,
      phenylephrine, and NPY, but not to mATP. In contrast, injection of the NO
      synthase inhibitor Nomega-nitro-l-arginine methyl ester, at a dose (10 mg kg(-1),
      iv) that lowered renal blood flow (by 47 +/- 4%) and elevated mean arterial
      pressure (by 28 +/- 8%), potentiated the renal vasoconstriction evoked by
      sympathetic nerve stimulation, phenylephrine, and NPY, but not mATP. It is
      concluded that endogenous NO may function as an inhibitory modulator of
      vasoconstrictor responses to the sympathetic cotransmitters norepinephrine and
      NPY. In contrast, NO seems not to modify vasoconstrictor responses to the
      sympathetic cotransmitter ATP, a discrepancy that may be due to differences in
      the types of receptors and intracellular effector mechanisms.

PMID- 11292360
TI  - Evidence that nitric oxide-induced synthesis of cGMP occurs in a paracrine but
      not an autocrine fashion and that the site of its release can be regulated:
      studies in dorsal root ganglia in vivo and in vitro.
AB  - As nitric oxide is a gas, it cannot be stored and has to be synthesized as
      required. This suggests that it could be released wherever nitric oxide synthase
      (NOS) is activated and due to its unstable state will react with appropriate
      targets at this site of production. In both dissociated dorsal root ganglion
      (DRG) cultures and in acutely isolated, but intact, DRG, treatment with capsaicin
      or bradykinin caused cGMP synthesis, which could be blocked by NOS inhibitors.
      The cGMP was synthesized in cells different from those expressing the neuronal
      isoform of NOS (nNOS). In dissociated cultures many of the cells stimulated to
      produce cGMP were neurons, whereas in isolated ganglia they were always satellite
      glia cells. Surprisingly, the satellite glia cells surrounding the nNOS
      containing neurons did not contain cGMP. Following nerve section in adult rats,
      many axotomized ganglion neurons expressed nNOS. Again in these axotomized
      ganglia, most cGMP was expressed in the satellite glia surrounding nNOS-negative
      neurons. However, an nNOS-selective inhibitor reduced the cGMP present in these
      axotomized ganglia, suggesting that the cGMP synthesized is stimulated by NO
      (nitrogen monoxide) produced by nNOS. In both dissociated cultures and axotomized
      ganglia, nNOS-containing processes were observed close to cGMP-positive cells.
      These observations lead to the suggestion that NO acts in a paracrine fashion
      when stimulating the synthesis of cGMP and may not be synthesized at all sites
      containing nNOS.

PMID- 11292361
TI  - Characterization of the radical product formed from the reaction of nitric oxide
      with the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate.
AB  - Previously, 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) has been used in
      combination with electron paramagnetic resonance (EPR) spectrometry to trap
      nitric oxide (NO(*)). The reaction between DBNBS and NO(*) yields a radical
      product which gives rise to an EPR signal consisting of three lines with an A(N)
      = 0.96 mT, but the structure of this product is unknown. A two-stage high
      performance liquid chromatography fractionation was performed to isolate the
      radical product from the other components in the DBNBS/NO(*) reaction mixture.
      The fractions containing the radical product were identified by the presence of
      the three-line EPR signal, and then these fractions were analyzed by negative ion
      fast atom bombardment-mass spectrometry (FAB-MS). Collectively, the FAB-MS data
      suggested that the radical product is the monosodium electrostatic complex with
      the dianion, bis(2,6-dibromo-4-sulfophenyl) nitroxyl. Analysis of the Gaussian
      and Lorentzian linewidths of the EPR signal suggested that bis(2,6-dibromo-4
      sulfophenyl) nitroxyl molecules may group together to form micelles. Further
      studies also indicated that significant amounts of nitrogen and nitrate were
      produced during the reaction between DBNBS and NO(*). A reaction scheme
      consistent with these results is presented.

PMID- 11292362
TI  - Identification of respiratory complexes I and III as mitochondrial sites of
      damage following exposure to ionizing radiation and nitric oxide.
AB  - In 32D cl 3 hematopoietic progenitor cells, the overexpression of manganese
      superoxide dismutase (MnSOD, SOD2), the enzyme normally found in mitochondria,
      protects against the damaging effects of ionizing radiation. In the presence of a
      nitric oxide donor, which exacerbates the damage, inhibition of mitochondrial
      function can be demonstrated to be associated with respiratory complexes I (NADH
      dehydrogenase) and III (cytochrome c reductase), but not II (succinate
      dehydrogenase), IV (cytochrome c oxidase), or V (ATP synthase). The same pattern
      of inhibition is observed in the case of isolated bovine heart mitochondria
      exposed to ionizing radiation and the nitric oxide donor. The addition of
      authentic peroxynitrite (ONO2(-)) to isolated mitochondria also results in damage
      to complexes I and III (but not II, IV, and V), as shown by assays of electron
      transfer activities and electron paramagnetic resonance (EPR) spectroscopic
      measurements, suggesting ONO2(-) to be responsible for most of the observed
      radiation damage in both the cultured cell lines and isolated mitochondria. It is
      argued that, in general, production of ONO2(-) is an important contributor to
      radiation damage in biological systems and the implications of these findings in
      relation to possible mechanisms of oxidant-linked apoptosis are briefly
      considered.

PMID- 11292363
TI  - Protection of primary glial cells by grape seed proanthocyanidin extract against
      nitrosative/oxidative stress.
AB  - Previous studies showed that proanthocyanidins provide potent protection against
      oxidative stress. Here we investigate the effects of grape seed proanthocyanidin
      extract (GSPE) as a novel natural antioxidant on the generation and fate of
      nitric oxide (NO) in rat primary glial cell cultures. GSPE treatment (50 mg/L)
      increased NO production (measured by NO(2-) assay) by stimulation of the
      inducible isoform of NOS. However, GSPE failed to affect the LPS/IFN-gamma
      induced NO production or iNOS expression. Similar responses were found in the
      murine macrophage cell line RAW264.7. GSPE did not show any effect on
      dihydrodichlorofluorescein fluorescence (ROS marker with high sensitivity toward
      peroxynitrite) either in control or in LPS/IFN-gamma-induced glial cultures even
      in the presence of a superoxide generator (PMA). GSPE treatment alone had no
      effect on the basal glutathione (GSH) status in glial cultures. Whereas the
      microglial GSH level declined sharply after LPS/IFN-gamma treatment, the
      endogenous GSH pool was protected when such cultures were treated additionally
      with GSPE, although NO levels did not change. Glial cultures pretreated with GSPE
      showed higher tolerance toward application of hydrogen peroxide (H(2)O(2)) and
      tert-butylhydroperoxide. Furthermore, GSPE-pretreated glial cultures showed
      improved viability after H(2)O(2)-induced oxidative stress demonstrated by
      reduction in lactate dehydrogenase release or propidium iodide staining. We
      showed that, in addition to its antioxidative property, GSPE enhances low-level
      production of intracellular NO in primary rat astroglial cultures. Furthermore,
      GSPE pretreatment protects the microglial GSH pool during high output NO
      production and results in an elevation of the H(2)O(2) tolerance in astroglial
      cells.

PMID- 11292364
TI  - In vivo and in vitro effects of lysine clonixinate on nitric oxide synthase in
      LPS-treated and untreated rat lung preparations.
AB  - Recent studies have shown that some nonsteroidal antiinflammatory drugs (NSAIDS)
      inhibited the inducible NO synthase (iNOS) without direct effect on the catalytic
      activity of this enzyme. This study was conducted to investigate the in vitro and
      in vivo effects of lysine clonixinate (LC) and indomethacin (INDO) on NOS
      activity in rat lung preparation. LC is a drug with antiinflammatory,
      antipyretic, and analgesic action. In the in vitro experiments, rats were
      injected with saline or lipopolysaccharide (LPS) and killed 6 h after treatment.
      Lung preparations were incubated with LC at 2.3 x 10(-5) M or 3.8 x 10(-5) M. The
      minimum concentration did not modify NOS activity in control or LPS-treated rats
      but the maximum dose inhibited increased NO production induced by LPS.
      Furthermore, INDO at 10(-6) M had no effect on enzymatic activity in control or
      LPS-treated rats. In the in vivo experiments, 40 mg/kg of LC were injected ip.
      Such a dose did not affect basal production of NO. When LC and LPS were injected
      simultaneously 6 h before sacrifice, a significant decrease in LPS-induced NOS
      activity was observed. INDO 10 mg/kg injected in control animals had no effect on
      NOS activity and did not block LPS induced stimulation of NO production when
      injected simultaneously. Finally, when LC (40 mg/kg) was injected 3 h after LPS,
      the enzymatic activity remained unchanged. Expression of iNOS was detected by
      Western blotting in rats treated with LPS plus 4, 10, 20, and 40 mg/kg of LC. The
      lowest dose was the only one showing no effect on LPS-induced increase of iNOS.
      In short, LC is a NSAID with inhibitory action on the expression of LPS-induced
      NOS, effect that was not seen with INDO in our experimental conditions.

PMID- 11292365
TI  - Combined effect of propofol and GSNO on oxidative phosphorylation of isolated rat
      liver mitochondria.
AB  - Isolated rat liver mitochondria have been treated with the general anaesthetic
      propofol (2,6-diisopropylphenol, 200 microM) and the physiological NO donor
      nitrosoglutathione (GSNO, 200 or 250 microM). The efficiency of the oxidative
      phosphorylation has been evaluated by measuring the respiration and ATP synthesis
      rates and the behavior of transmembrane electrical potential. In mitochondria
      energized by succinate, the simultaneous presence of both propofol and GSNO gives
      rise to a synergic action in affecting the resting and the ADP-stimulated
      respiration, the respiratory control ratio, the ATP synthesis, and the formation
      and utilization of the electrochemical transmembrane potential.

PMID- 11292366
TI  - Nitric oxide initiates iron binding to neocuproine.
AB  - It was demonstrated that two species of paramagnetic dinitrosyl iron complex
      (DNIC) with neocuproine form under the following conditions: in addition of
      neocuproine to a solution of DNIC with phosphate; in gaseous NO treatment of a
      mixture of Fe(2+) + neocuproine aqueous solutions at pH 6.5-8; and in addition of
      Fe(2+)--citrate complex + neocuproine to a S-nitrosocysteine (cys-NO) solution.
      The first form of DNIC with neocuproine is characterized by an EPR signal with g
      factor values of 2.087, 2.055, and 2.025, when it is recorded at 77K. At room
      temperature, the complex displays a symmetric singlet at g = 2.05. The second
      form of DNIC with neocuproine gives an EPR signal with g-factor values of 2.042,
      2.02, and 2.003, which can be recorded at a low temperature only.The revealed
      complexes are close to DNIC with cysteine in their stability. The ability of
      neocuproine to bind Fe(2+) in the presence of NO with formation of paramagnetic
      DNICs warrants critical reevaluation of the statement that neocuproine is only
      able to bind Cu(+) ions. It was suggested that the observed affinity of
      neocuproine to iron was due to transition of Fe(2+) in DNIC with neocuproine to
      Fe(+). In experiments on cys-NO, it was shown that the stabilizing effect of
      neocuproine on this compound could be due to neocuproine binding to the iron
      catalyzing decomposition of cys-NO.

PMID- 11292367
TI  - Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase
      (NOS), but its function is not fully understood. Specifically, it is unclear
      whether BH4 participates directly in electron transfer. We investigated the redox
      properties of BH4 and several other pteridines with cyclic voltammetry and
      Osteryoung square wave voltammetry. BH4 was oxidized at a potential of +0.27 V vs
      normal hydrogen electrode (NHE); the corresponding reductive signal after the
      reversal of the scan direction was very small. Instead, reduction occurred at a
      potential of -0.16 V vs NHE; there was no corresponding oxidative signal. These
      two transitions were interdependent, indicating that the reductive wave at -0.16
      V represented the regeneration of BH4 from its product of oxidation at +0.27 V.
      Similar voltammograms were obtained with tetrahydroneopterin and 6,7
      dimethyltetrahydropterin, both of which can substitute for BH4 in NOS catalysis.
      Completely different voltammograms were obtained with 7,8-dihydrobiopterin,
      sepiapterin, 2'-deoxysepiapterin, and autoxidized BH4. These 7,8-dihydropterins,
      which do not sustain NOS catalysis, were oxidized at much higher potentials
      (+0.82-1.04 V vs NHE), and appreciable reduction did not occur between +1.2 and 
      0.8 V, in line with the concept of a redox role for BH4 in NOS catalysis.
      However, the electrochemical properties of the potent pterin-site NOS inhibitor 4
      amino-BH4 resembled those of BH4, whereas the active pterin cofactor 5-methyl-BH4
      was not re-reduced after oxidation. We conclude that the 2-electron redox cycling
      of the pterin cofactor between BH4 and quinonoid dihydrobiopterin is not
      essential for NO synthesis. The data are consistent with 1-electron redox cycling
      between BH4 and the trihydrobiopterin radical BH3(*).

PMID- 11292368
TI  - Caveolar localization of arginine regeneration enzymes, argininosuccinate
      synthase, and lyase, with endothelial nitric oxide synthase.
AB  - Although normal intracellular levels of arginine are well above the K(m), and
      should be sufficient to saturate nitric oxide synthase in vascular endothelial
      cells, nitric oxide production can, nonetheless, be stimulated by exogenous
      arginine. This phenomenon, termed the "arginine paradox," has suggested the
      existence of a separate pool of arginine directed to nitric oxide synthesis. In
      this study, we demonstrate that exogenous citrulline was as effective as
      exogenous arginine in stimulating nitric oxide production and that citrulline in
      the presence of excess intracellular and extracellular arginine further enhanced
      bradykinin stimulated endothelial nitric oxide production. The enhancement of
      nitric oxide production by exogenous citrulline could therefore be attributed to
      the capacity of vascular endothelial cells to efficiently regenerate arginine
      from citrulline. However, the regeneration of arginine did not affect the bulk
      intracellular arginine levels. This finding not only supports the proposal for a
      unique pool of arginine, but also suggested channeling of substrates that would
      require a functional association between nitric oxide production and arginine
      regeneration. To support this proposal, we showed that nitric oxide synthase, and
      the enzymes involved in arginine regeneration, argininosuccinate synthase and
      argininosuccinate lyase, cofractionated with plasmalemmal caveolae, a
      subcompartment of the plasma membrane. Overall, the results from this study
      strongly support the proposal for a separate pool of arginine for nitric oxide
      production that is defined by the cellular colocalization of enzymes involved in
      nitric oxide production and the regeneration of arginine.

PMID- 11292369
TI  - Modulation of cerebellar and hepatic nitric oxide synthase by exogenous arginine
      and endotoxin.
AB  - We have studied in mice the effect of treatment with exogenous arginine and/or
      LPS by monitoring serum nitrite/nitrate levels and by investigating the response
      of cerebellar and liver nitric oxide synthase (NOS). We measured NOS activity in
      cerebellar extracts while changes in iNOS mRNA were followed in the liver since
      direct assay of NOS activity proved unreliable with this tissue. In fact, liver
      and cerebellum extracts were both very active in converting arginine into a
      citrulline-like metabolite, but only cerebellum conversion was dependent on
      addition of NADPH and inhibitable by N(G)-methyl-l-arginine. Treatment with LPS,
      on its own, increased serum nitrite/nitrate levels at 5 and 20 h after injection,
      while treatment with LPS and arginine produced nitrite/nitrate levels in the
      serum even greater at 5 h, but significantly lower at 20 h. Liver iNOS mRNA
      levels were markedly increased by LPS, and this effect was significantly
      decreased when mice were also given exogenous arginine. A stimulatory effect of
      LPS was also found on NOS activity in the cerebellum, where a very small
      stimulation may have also been caused by arginine feeding. These findings
      indicate that LPS stimulates NOS expression/activity both in the cerebellum and
      in the liver and suggest a complex pattern of modulation of iNOS by arginine,
      with NO being first produced in excess and then downregulating iNOS expression.

PMID- 11292370
TI  - Time course of inducible nitric oxide synthase activity following endotoxin
      administration in dogs.
AB  - An increased production of nitric oxide (NO) via the inducible isoform of NO
      synthase (iNOS) has been incriminated in the pathogenesis of septic shock. Since
      the time course of iNOS activity is not known during endotoxic shock in dogs, we
      measured iNOS activity, estimated by the rate of conversion of (14)C-arginine to
      (14)C-citrulline in the absence of calcium, in the heart, lung, liver, kidney,
      and gut at 1, 2, 3, 4, and 6 h after a bolus of Escherichia coli endotoxin (2
      mg/kg, iv), in the dog. This model, including generous fluid administration, is
      associated with typical features of human septic shock, including low systemic
      vascular resistance, altered myocardial function and limited oxygen extraction
      capability. An increase in iNOS activity was observed at 4 h in the liver (0.24
      vs 0.04 mU/mg/min) and at 6 h in the heart (0.26 vs 0.09 mU/mg/min). These
      findings may contribute to a better delineation of the involvement of NO in
      endotoxic shock, and to the evaluation of the therapeutic effects of NO
      inhibitors.

PMID- 11292371
TI  - Cellular functions of proteoglycans--an overview.

PMID- 11292372
TI  - Cartilage proteoglycans.
AB  - The predominant proteoglycan present in cartilage is the large chondroitin
      sulfate proteoglycan 'aggrecan'. Following its secretion, aggrecan self-assembles
      into a supramolecular structure with as many as 50 monomers bound to a filament
      of hyaluronan. Aggrecan serves a direct, primary role providing the osmotic
      resistance necessary for cartilage to resist compressive loads. Other
      proteoglycans expressed during chondrogenesis and in cartilage include the cell
      surface syndecans and glypican, the small leucine-rich proteoglycans decorin,
      biglycan, fibromodulin, lumican and epiphycan and the basement membrane
      proteoglycan, perlecan. The emerging functions of these proteoglycans in
      cartilage will enhance our understanding of chondrogenesis and cartilage
      degeneration.

PMID- 11292373
TI  - Hyaluronan in morphogenesis.
AB  - Hyaluronan is a very large polysaccharide that is found in extracellular
      matrices, at the cell surface and inside cells. This review focuses on the
      functions of hyaluronan directly associated with the cell surface, where it is
      commonly present as the essential core of a highly hydrated pericellular matrix
      that contains several other components (hyaladherins) bound to hyaluronan. Three
      major molecular characteristics of hyaluronan contribute to its physiological
      functions: its unique hydrodynamic properties, its interactions with structural
      extracellular hyaladherins, and its instructive effects on cell signaling and
      behavior. Recent studies of hyaluronan-deficient mouse embryos illustrate the
      importance of each of these classes of function of hyaluronan. It is postulated
      that the morphogenetic effects of hyaluronan are due to its ability to act as a
      template for assembly of a multi-component, pericellular matrix as well as to its
      physical properties. This matrix would provide a hydrated environment in which
      cells are separated from structural barriers to morphogenetic changes and receive
      signals from hyaluronan itself and from associated factors.

PMID- 11292374
TI  - Heparan sulfate proteoglycans in invasion and metastasis.
AB  - Because heparan sulfate proteoglycans mediate cell adhesion and control the
      activities of numerous growth and motility factors, they play a critical role in
      regulating the metastatic behavior of tumor cells. Due to their utilitarian
      nature, heparan sulfate proteoglycans may at times act as inhibitors of cell
      invasion and at other times as promoters of cell invasion, with their function
      being determined by their location (cell surface or extracellular matrix), the
      heparin-binding molecules they associate with, the presence of modifying enzymes
      (proteases, heparanases) and the precise structural characteristics of the
      proteoglycan. Also, the tissue type and pathophysiological state of the tumor
      influence proteogylcan function. This review summarizes our current knowledge of
      the role heparan sulfate proteoglycans play in regulating tumor cell metastasis,
      proposes mechanisms of how these molecules function and examines the potential
      for discovery of new therapeutic approaches designed to block metastatic cancer.

PMID- 11292375
TI  - Heparan sulfate proteoglycans in the nervous system: their diverse roles in
      neurogenesis, axon guidance, and synaptogenesis.
AB  - Development of the mammalian nervous system involves generation of neurons from
      neural stem cells, migration of generated neurons toward genetically determined
      locations, extension of axons and dendrites, and establishment of neuronal
      connectivity. Recent progresses revealed diverse role of heparan sulfate
      proteoglycans in these processes. This article reviews our current knowledge
      about the functional roles of heparan sulfate proteoglycans in three critical
      events in mammalian neural development, namely neurogenesis, axon guidance, and
      synapse development.

PMID- 11292376
TI  - Molecular interactions of syndecans during development.
AB  - The syndecans, cell surface heparan sulfate proteoglycans (HSPGs), bind numerous
      ligands via their HS glycosaminoglycan chains. The response to this binding is
      flavored by the identity of the core protein that bears the HS chains. Each of
      the syndecan core proteins has a short cytoplasmic domain that binds cytosolic
      regulatory factors. The syndecans also contain highly conserved transmembrane
      domain and extracellular domains for which important activities are slowly
      emerging. These protein domains, which will be the focus of this review, localize
      the syndecan to sites at the cell surface during development where they
      collaborate with other receptors to regulate signaling and cytoskeletal
      organization.

PMID- 11292377
TI  - Developmental roles of the glypicans.
AB  - Glypicans are proteins with very characteristic structures that are substituted
      with heparan sulfate and that are linked to the cell surface via
      glycosylphosphatidylinositol. The modular structure of the glypicans has been
      highly conserved throughout evolution. Six glypicans have been identified so far
      in vertebrates. Mutations in Drosophila, humans and mice reveal a role for these
      cell surface molecules in the control of cell growth and differentiation. Their
      mechanism of action is not yet clear. Most likely, glypicans activate or
      determine the activity ranges of morphogens and growth factors such as FGFs,
      BMPs, Wnts, Hhs and IGFs.

PMID- 11292378
TI  - Genetic dissection of proteoglycan function in Drosophila and C. elegans.
AB  - Genetic analysis of the signaling pathways that govern patterning during
      development in the fruitfly Drosophila melanogaster and in the nematode C.
      elegans have provided insight into the in vivo functions of proteoglycans and
      their associated glycosaminoglycans. These studies have shown that patterning
      events dictated by Fibroblast Growth Factor Receptors, Wnt, Transforming Growth
      Factor- beta(TGF- beta), and Hedgehog families of growth factors are regulated by
      proteoglycans. Recent biochemical and structural analyses have shown that the
      molecular machinery of glycosaminoglycan biosynthesis is highly conserved between
      these invertebrate organisms and mammals. Drosophila and C. elegans therefore
      provide powerful model systems for exploring the varied functions proteoglycans
      and their glycosaminoglycan modifications.

PMID- 11292379
TI  - Introduction. Trafficking of lipids.

PMID- 11292380
TI  - Lipid distribution and transport across cellular membranes.
AB  - In eukaryotic cells, the membranes of different intracellular organelles have
      different lipid composition, and various biomembranes show an asymmetric
      distribution of lipid types across the membrane bilayer. Membrane lipid
      organization reflects a dynamic equilibrium of lipids moving across the bilayer
      in both directions. In this review, we summarize data supporting the role of
      specific membrane proteins in catalyzing transbilayer lipid movement, thereby
      controlling and regulating the distribution of lipids over the leaflets of
      biomembranes.

PMID- 11292381
TI  - Membrane domains and polarized trafficking of sphingolipids.
AB  - The plasma membrane of polarized cells consists of distinct domains, the apical
      and basolateral membrane, that are characterized by a distinct lipid and protein
      content. Apical protein transport is largely mediated by (glyco)sphingolipid-
      cholesterol enriched membrane microdomains, so called rafts. In addition changes
      in the direction of polarized sphingolipid transport appear instrumental in cell
      polarity development. Knowledge is therefore required of the mechanisms that
      mediate sphingolipid sorting and the complexity of the trafficking pathways that
      are involved in polarized transport of both sphingolipids and proteins. Here we
      summarize specific biophysical properties that underly mechanisms relevant to
      sphingolipid sorting, cargo recruitment and polarized trafficking, and discuss
      the central role of a subapical compartment, SAC or common endosome (CE), as a
      major intracellular site involved in polarized sorting of sphingolipids, and in
      development and maintenance of membrane polarity.

PMID- 11292382
TI  - Uptake and metabolism of exogenous glycosphingolipids by cultured cells.
AB  - Exogenous glycosphingolipids, especially gangliosides, are used to study
      transport and metabolism of their endogenous counterparts as well as their role
      in cell adhesion, cell recognition and signal transduction. Unlike monodispersed
      solutes, in aqueous media ganglioside molecules aggregate into micelles (or
      bilayer structures) with a very low critical micellar concentration. Upon
      addition to cells in culture, exogenous gangliosides bind to the cell surface in
      three operationally defined modes: loosely associated micelles removable by
      serum; tightly attached micelles removable by proteases such as trypsin; and
      ganglioside molecules inserted into the outer leaflet of the plasma membrane. As
      shown by a biotin-labeled derivative of the ganglioside GM1 these inserted
      molecules are endocytosed and transported to intralysosomal membranes for
      catabolism. The benefit from using (partially) nondegradable as well as semi
      truncated glycosphingolipids in transport studies is discussed.

PMID- 11292383
TI  - Lipid domains in the endocytic pathway.
AB  - Whereas endosomes connect with both exocytic and endocytic organelle via
      extensive lipid and protein traffic, each endosome has a distinct lipid and
      protein composition. Recent observations suggest that different lipid membrane
      domains exist even in the same endosome. These lipid domains, together with low
      pH milieu, may present a variety of micro-environments to cargo molecules.
      Evidence is accumulating which suggests that the alteration of these lipid
      microdomains may be involved in a number of pathological conditions.

PMID- 11292384
TI  - Phosphatidylinositol transfer proteins couple lipid transport to phosphoinositide
      synthesis.
AB  - Phosphatidylinositol transfer proteins (PITPs) are lipid binding proteins that
      can catalyse the transfer of phosphatidylinositol (PI) from membranes enriched in
      PI to PI-deficient membranes. Three soluble forms of PITP of 35--38 kDa (PITP
      alpha, PITP beta and rdgB beta) and two larger integral proteins of 160 kDa (rdgB
      alpha I and II), which contain a PITP domain, are found in mammalian cells. PITPs
      are intimately associated with the compartmentalised synthesis of different
      phosphorylated inositol lipids. PI is the primary inositol lipid that is
      synthesised at the endoplasmic reticulum and is further phosphorylated in
      distinct membrane compartments by many specific lipid kinases to generate seven
      phosphorylated inositol lipids which are required for both signalling and for
      membrane traffic. PITPs play essential roles in both signalling via phospholipase
      C and phosphoinositide 3-kinases and in multiple aspects of membrane traffic
      including regulated exocytosis and vesicle biogenesis.

PMID- 11292385
TI  - Intracellular trafficking and turnover of phosphatidylinositol 3-phosphate.
AB  - Phosphatidylinositol 3-kinases (PI 3-kinases) regulate cellular functions through
      the 3'-phosphorylation of phosphatidylinositol (PI) and its derivatives. The PI 3
      kinase product phosphatidylinositol 3-phosphate [PI(3)P] functions to recruit and
      activate effector proteins containing FYVE zinc finger domains. These proteins
      have various functions in endocytic membrane trafficking, cytoskeletal regulation
      and signal transduction. In order to understand the function of FYVE proteins, it
      is essential to study the formation, localisation, trafficking and turnover of
      PI(3)P. Here we review recent evidence that PI(3)P is formed on early endosomes
      through the activity of a PI 3-kinase which is recruited by the GTPase Rab5, and
      that the PI(3)P is subsequently internalised into intralumenal vesicles of
      multivesicular endosomes for turnover.

PMID- 11292386
TI  - Early and delayed afterdepolarizations in rabbit heart Purkinje cells viewed by
      confocal microscopy.
AB  - We investigated action potentials and Ca(2+) transients in rabbit Purkinje
      myocytes using whole cell patch clamp recordings and a confocal microscope.
      Purkinje cells were loaded with 5 microM Fluo-3/AM for 30min. Action potentials
      were elicited by application of a stimulus delivered through the recording
      pipettes. When Purkinje cells were stimulated in 2.0mM Ca(2+), transverse XT line
      scans revealed a symmetrical 'U'-shaped Ca(2+) transient demonstrating that the
      transient was initiated at the cell periphery. When Purkinje cells were
      superfused with 1 microM isoprenaline, both early and delayed
      afterdepolarizations were induced. XT line scans of cells exhibiting early
      afterdepolarizations showed a second symmetrical 'U'-shaped transient. This
      Ca(2+) transient was initiated at the cell periphery suggesting reactivation of
      the Ca(2+) current. In contrast, in Purkinje cells exhibiting delayed
      afterdepolarizations and a corresponding transient inward current, XT line scans
      revealed a heterogenous rise in Ca(2+) at both peripheral and central regions of
      the cell. Immunofluorescence staining of Purkinje cells with an antibody to
      ryanodine receptors (RyRs) revealed that RyRs are located at regularly spaced
      intervals throughout the interior of Purkinje cells. These results suggest that,
      although RyRs are located throughout Purkinje cells, only peripheral RyRs are
      activated to produce transients, sparks and early afterdepolarizations. During
      delayed afterdepolarizations, we observed a heterogenous rise in Ca(2+) at both
      peripheral and central regions of the cell as well as large central increases in
      Ca(2+). Although the latter may result from central release, we cannot exclude
      the possibility that it reflects Ca(2+) diffusion from subsarcolemmal sites.

PMID- 11292387
TI  - ATP induces intracellular calcium increases and actin cytoskeleton disaggregation
      via P2x receptors.
AB  - The consequences of purinoceptor activation on calcium signalling, inositol
      phosphate metabolism, protein secretion and the actin cytoskeleton were
      demonstrated in the WRK-1 cell line. Extracellular ATP was used as a secretagogue
      to induce a rise in intracellular Ca(2+) concentration ([Ca(2+)](i)), acting via
      P2x purinergic receptors, which causes actin skeleton disaggregation and protein
      secretion. ATP bound specifically to purinergic receptors, with Ki of 0.8 microM.
      The magnitude order for binding of different nucleotides was alpha beta-Met-ATP
      >or= dATPalphaS > ATP >or= ADP > UTP > AMP > suramin. No increase in inositol
      phosphates (IPs) was observed after ATP application suggesting that the
      purinergic sites in WRK-1 cells are not of a P2y type. ATP (1-100 microM) caused
      a concentration-dependent increase in [Ca(2+)](i)(EC(50)= 30 microM). The
      responses were reproducible without any desensitization over several
      applications. The response to ATP was abolished when extracellular calcium
      ([Ca(2+)](e)) was reduced to 100 nM. A non-specific purinergic antagonist,
      suramin, reversibly inhibited the ATP-response suggesting that ATP is able to
      bind to P2x purinergic sites to trigger Ca(2+) entry and increase of [Ca(2+)](i).
      ATP induced a concentration-dependent disaggregation of actin and exocytotic
      release of proteins both, which were dependent upon [Ca(2+)](e). Similarly,
      alpha,beta-Met-ATP, a potent P2x agonist also stimulated Ca(2+) mobilization,
      actin network destructuration, and protein release. In the isolated rat
      neurohypophysial nerve terminals, ATP was shown to act as a physiological
      stimulus for vasopressin release via Ca(2+) entry through a P2x receptor [6].
      Here, we show that in these nerve terminals, ATP is also able to induce actin
      disaggregation by a Ca(2+) dependent mechanism. Thus, actin cytoskeleton
      alterations induced by ATP through activation of P2x receptors could be a prelude
      to exocytosis.

PMID- 11292388
TI  - Analysis of Mn(2+)/Ca(2+) influx and release during Ca(2+) oscillations in mouse
      eggs injected with sperm extract.
AB  - Repetitive Ca(2+) release from the endoplasmic reticulum (ER) is necessary for
      activation of mammalian eggs. Influx and release of Mn(2+) and Ca(2+) during
      Ca(2+) oscillations induced by injection of sperm extract (SE) into mouse eggs
      were investigated by Mn(2+)-quenching of intracellular Fura-2 after adding Mn(2+)
      to external medium. Mn(2+)/Ca(2+) influx was detected at the resting state. A
      marked Mn(2+)/Ca(2+) influx occurred during the first Ca(2+) release upon SE
      injection, and persistently facilitated Mn(2+)/Ca(2+) influx was observed during
      steady Ca(2+) oscillations. As intracellular Mn(2+) concentration ([Mn(2+)](i))
      increased progressively, periodic [Mn(2+)](i) rises appeared, corresponding to
      each Ca(2+)transient but taking a slower time course. A numerical simulation
      based on continuous Mn(2+)/Ca(2+) influx-extrusion across the plasma membrane and
      release-uptake across the ER membrane in a competitive manner mimicked well the
      Mn(2+) oscillations calculated from experimental data, strongly suggesting that
      repetitive Mn(2+) release develops after Mn(2+) entry and uptake into the ER. In
      other experiments, a marked Mn(2+) influx occurred upon Mn(2+) addition to Ca(2+)
      free medium after depletion of the ER using an ER Ca(2+) pump inhibitor plus
      repeated injection of inositol 1,4,5-trisphosphate (InsP(3)). No significant
      increase in Mn(2+) influx was induced by injection of SE, InsP(3), or Ca(2+),
      when Ca(2+) release was prevented by pre-injection of an antibody against the
      InsP(3) receptor. We concluded that Ca(2+) influx is activated during the initial
      large Ca(2+)release possibly by a capacitative mechanism and kept facilitated
      during steady Ca(2+) oscillations. The finding that repetitive Mn(2+) release is
      caused by continuous Mn(2+) entry suggests that continuous Ca(2+) influx may play
      a critical role in refilling the ER and, thereby, maintaining Ca(2+)oscillations
      in mammalian fertilization.

PMID- 11292389
TI  - Graded alpha1-adrenoceptor activation of arteries involves recruitment of smooth
      muscle cells to produce 'all or none' Ca(2+) signals.
AB  - Confocal laser scanning microscopy and Fluo-4 were used to visualize Ca(2+)
      transients within individual smooth muscle cells (SMC) of rat resistance arteries
      during alpha(1)-adrenoceptor activation. The typical spatio-temporal pattern of
      [Ca(2+)] in an artery after exposure to a maximally effective concentration of
      phenylephrine (PE, 10.0 microM) was a large, brief, relatively homogeneous Ca(2+)
      transient, followed by Ca(2+) waves, which then declined in frequency over the
      course of 5 min and which were asynchronous in different SMC. Concentration
      Effect (CE) curves relating the concentration of PE (range: 0.1 microM to 10.0
      microM) to the effects (fraction of cells producing at least one Ca(2+) wave, and
      number of Ca(2+) waves during 5 min) had EC(50) values of approximately 0.5
      microM and approximately 1.0 microM respectively. The initial Ca(2+) transient
      and the subsequent Ca(2+) waves were abolished in the presence of caffeine (10.0
      mM). A repeated exposure to PE, 1.5 min after the first had ended, elicited fewer
      Ca(2+) waves in fewer cells than did the initial exposure. Caffeine-sensitive
      Ca(2+) stores were not depleted at this time, however, as caffeine alone was
      capable of inducing a large release of Ca(2+)1.5 min after PE. In summary, the
      mechanism of a graded response to graded alpha(1)-adrenoceptor activation is the
      progressive 'recruitment' of individual SMC, which then respond in 'all or none'
      fashion (viz. asynchronous Ca(2+) waves). Ca(2+) signaling continues in the
      arterial wall throughout the time-course (at least 5 min) of activation of
      alpha(1)-adrenoceptors. The fact that the Ca(2+) waves are asynchronous accounts
      for the previously reported fall in 'arterial wall [Ca(2+)]' (i.e. spatial
      average [Ca(2+)] over all cells).

PMID- 11292390
TI  - InsP(3)-induced Ca(2+) release in permeabilized invertebrate photoreceptors: a
      link between phototransduction and Ca(2+) stores.
AB  - Using the low-affinity fluorescent Ca(2+) indicators, Mag-Fura-2 and Mag-Fura
      Red, we studied light- and InsP(3)-induced Ca(2+) release in permeabilized
      microvillar photoreceptors of the medicinal leech, Hirudo medicinalis. Two major
      components of the phosphoinositide signaling pathway, phospholipase-C and the
      InsP(3) receptor, were characterized immunologically and appropriately localized
      in photoreceptors. Whereas phospholipase-C was abudantly expressed in
      photoreceptive microvilli, InsP(3) receptors were found mostly in submicrovillar
      endoplasmic reticulum (SER). Permeabilization of the peripheral plasma membrane
      with saponin allowed direct measurements of luminal free Ca(2+) concentration
      (Ca(L)) changes. Confocal Ca(2+) imaging using Mag-Fura Red demonstrated that
      Ins(1,4,5)P(3) mobilizes Ca(2+) from SER. As detected with Mag-Fura-2, a brief
      50ms light flash activated rapid Ca(2+) depletion of SER, followed by an
      effective refilling within 1min of dark adaptation after the light flash.
      Sensitivity to Ins(1,4,5)P(3) of the Ca(2+) release from SER in leech
      photoreceptors was accompanied by irreversible uncoupling of phototransduction
      from Ca(2+) release. Depletion of Ca(2+) stores was induced by
      Ins(1,4,5)P(3)(EC(50)= 4.75 microM) and the hyper-potent agonist adenophostin A
      (EC(50)/40nM) while the stereoisomer L-myo Ins(1,4,5)P(3) was totally inactive.
      Ins(1,4,5)P(3)- or adenophostin A-induced Ca(2+) release was inhibited by 0.1
      1mg/ml heparin. The Ca(2+) pump inhibitors, cyclopiazonic acid and thapsigargin,
      in the presence of Ins(1,4,5)P(3), completely depleted Ca(2+) stores in leech
      photoreceptors.

PMID- 11292391
TI  - Anti-adrenergic effect of adenosine on Na(+)-Ca(2+) exchange current recorded
      from guinea-pig ventricular myocytes.
AB  - The Na(+)-Ca(2+) exchanger is a protein present in the cell membrane of many cell
      types. In heart it plays important roles in Ca homeostasis and ionic current
      generation. Recently, it has been reported that the beta-adrenergic agonist
      isoprenaline (ISO) can increase directly Na(+)-Ca(2+) exchanger activity in
      guinea-pig ventricular myocytes. Adenosine (ADO) exerts anti-adrenergic
      properties that make it effective against some arrhythmias and the aim of the
      present study was to determine whether or not ADO can antagonize the direct
      modulatory effect of ISO on the exchanger.Whole-cell patch clamp measurements of
      Na(+)-Ca(2+) exchanger current (I(NaCa)) were made from guinea-pig ventricular
      myocytes, with major interfering currents inhibited. I(NaCa) was measured at 378
      degrees C as current sensitive to external nickel (Ni(2+), 10 mM) during an
      applied descending voltage ramp. ISO (1 microM) significantly increased both
      inward and outward I(NaCa). This effect was abolished in the presence of ADO (200
      microM). ADO alone did not significantly alter the amplitude of I(NaCa). The
      effect of ADO on the response of I(NaCa) to ISO was mimicked by the A(1)ADO
      receptor agonist N(6)-cyclopentyladenosine (CPA, 10 microM), whereas the effect
      of ADO on the response of I(NaCa) to ISO was inhibited by the A(1)ADO receptor
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 microM). These data
      suggest that the A(1)ADO receptor mediated the response. The anti-adrenergic
      effects on I(NaCa) of ADO were not affected by the protein kinase C (PKC)
      inhibitor, chelerythrine (CLT, 1 microM), nor by the nitric oxide (NO) synthase
      inhibitor, N (G)-nitro-L-arginine methyl ester((L)-NAME, 0.5 mM). Moreover, in
      the presence of PKC activator phorbol 12-myristate 13-acetate (PMA, 1 microM) or
      exogenous NO donor sodium nitroprusside (SNP, 100 microM), ISO preserved its
      stimulatory effect on I(NaCa). However, prior incubation of myocytes with
      pertussis toxin (PTX, 5 microg ml(-1) did prevent the effect of ADO. The anti
      adrenergic effect of ADO on I(NaCa) was mimicked by externally applied carbachol
      (CCh, 10 microM), a muscarinic receptor agonist. We conclude that ADO antagonized
      the effect of beta-adrenergic stimulation of I(NaCa) by directly activating
      inhibitory G-protein (G(i))-linked A(1) receptors in guinea-pig ventricular
      myocytes. These findings may suggest a novel mechanism by which adenosine exerts
      some of its antiarrhythmic effects.

PMID- 11292392
TI  - Ca(2+) entry into primary cultured pig coronary smooth muscle cells after
      previous store depletion by repetitive P2Y purinoceptor stimulation.
AB  - Store-operated Ca(2+) entry, stimulated by depletion of intracellular Ca(2+)
      pools, has not been fully elucidated in vascular smooth muscle cells of pig
      coronary arteries. Therefore, [Ca(2+)](i) was measured in cultured cells derived
      from extramural pig coronary arteries using the Fura-2/AM fluorometry. Divalent
      cation entry was visualized with the Fura-2 Mn(2+)-quenching technique. Ca(2+)
      stores were depleted either by repetitive stimulation of P2Y purinoceptors with
      ATP (10 micromol/L), or by the sarcoendoplasmic Ca(2+)-ATPase inhibitor 2,5-Di
      (tert-butyl)-1,4-benzohydroquinone (BHQ; 1 micromol/L) in Ca(2+)-free medium
      (EGTA 1 mmol/L). Addition of Ca(2+)(1 mmol/L) induced refilling of ATP-sensitive
      Ca(2+) stores and an increase in [Ca(2+)](i) in the presence of BHQ. Both could
      be significantly diminished by Ni(2+)(5 and 1mmol/L), La(3+)(10 micromol/L),
      Gd(3+)(10 micromol/L), and Mg(2+)(5.1 mmol/L). In contrast to the BHQ-mediated
      rise in [Ca(2+)](i), refilling of ATP-depleted stores was affected by neither
      flufenamate (0.1 mmol/L), nor by nitrendipine, nifedipine, and nisoldipine (each
      1 micromol/L). The data suggest that after store depletion in pig coronary smooth
      muscle cells ATP and BHQ may converge on a common, Ni(2+)-, La(3+)-, Gd(3+)-, and
      Mg(2+)- sensitive Ca(2+) entry pathway, i.e. on a store-operated Ca(2+) entry. An
      additional contribution of the Na(+)/Ca(2+) exchanger cannot be excluded.
      Flufenamate-sensitive non-selective cation channels and dihydropyridine-sensitive
      L-type Ca(2+) channels are not involved in refilling of Ca(2+) stores after
      previous depletion by repetitive P2Y purinoceptor stimulation. The store-operated
      Ca(2+) entry in-between repetitive purinoceptor stimulation, i.e. in the absence
      of the agonist, may be responsible for the maintenance of agonist-induced
      rhythmic Ca(2+) responses.

PMID- 11292401
TI  - Attempted eyelid closure affects intraocular pressure measurement.
AB  - PURPOSE: To evaluate the effect of attempted eyelid closure on intraocular
      pressure measurement. METHODS: Normal subjects underwent intraocular pressure
      measurement in both eyes using Goldmann applanation tonometry and Tono-pen XL
      (Mentor, Inc, Norwell, Massachusetts) by the same examiner holding the eyelids
      open, both with and without the subject simultaneously attempting forced eyelid
      closure. Subjects were seated during all measurements and waited 5 minutes
      between measurements with each instrument; the order of measurement was
      randomized. RESULTS: Thirty eyes of 15 subjects (six men, nine women) were
      enrolled. Mean age was 30.5 +/- 5.2 years (range, 24 to 40 years). With Goldmann
      applanation tonometry, intraocular pressure increased in both eyes with attempted
      eyelid closure by a mean of 1.5 +/- 2.0 mm Hg (P =.0002, paired t test; range, -2
      to 8 mm Hg). With the Tono-pen XL, intraocular pressure also increased in both
      eyes with attempted eyelid closure by a mean of 1.9 +/- 2.7 mm Hg (P =.0002,
      paired t test; range, -2 to 9 mm Hg). Tono-pen XL mean intraocular pressure
      values in both eyes (14.4 +/- 2.3 mm Hg) consistently overestimated those of
      Goldmann applanation tonometry (13.0 +/- 2.2 mm Hg) by a mean of 1.4 +/- 2.3 mm
      Hg. CONCLUSIONS: Attempted forced eyelid closure is a common and statistically
      significant source of error in routine outpatient measurement of intraocular
      pressure and could influence clinical management of glaucoma.

PMID- 11292402
TI  - T cell subsets and sIL-2R/IL-2 levels in patients with glaucoma.
AB  - PURPOSE: We hypothesize that cellular immunity may have a previously unrecognized
      role in glaucomatous optic neuropathy. The purpose of this study is to analyze
      subsets of T cells and the levels of cytokine IL-2 and the soluble IL-2 receptor
      in peripheral blood from patients with normal pressure glaucoma (NPG) or primary
      open angle glaucoma (POAG) in comparison to age-matched control subjects.
      METHODS: In this study, 38 patients (20 NPG; 18 POAG) and 19 controls were
      included. sIL-2R and IL-2 were assayed by ELISA. T cell subsets were analyzed by
      flow cytometry and lymphocyte proliferation was used to measure the reactive
      ability of T cells to phytohemagglutinin (PHA). RESULTS: The frequency of
      CD8(+)HLA-DR(+) lymphocytes were increased in patients with NPG (P = 0.008), and
      CD3(+)CD8(+) lymphocytes increased in both NPG (P = 0.03) and POAG patients (P =
      0.0004). CD5(+) lymphocytes were higher only in POAG patients (P = 0.0012). In
      comparison to controls, the ratio of CD4(+)/CD8(+) lymphocytes was similar in
      both groups. The mean concentrations of sIL-2R in NPG (P = 0.011) and POAG (P =
      0.0023) patients were higher than that found in control subjects although IL-2
      concentrations were similar in these groups. In addition, the reactive ability of
      T lymphocytes to the non-specific reagent (PHA) was reduced significantly in NPG
      (P = 0.02) and POAG patients (P=0.04). CONCLUSION: The alterations of the
      cellular immune system in patients with glaucoma support our hypothesis that the
      immune system may play an important role in the initiation and/or sustainment of
      glaucomatous optic neuropathy in some patients.

PMID- 11292403
TI  - Autologous ipsilateral rotating penetrating keratoplasty.
AB  - PURPOSE: To evaluate visual outcome after autologous ipsilateral rotating
      penetrating keratoplasty. METHODS: The study included nine patients who
      consecutively underwent autologous ipsilateral rotating penetrating keratoplasty
      for treatment of traumatic central corneal avascular scars. These patients were
      compared with 105 patients who consecutively underwent homologous central
      penetrating keratoplasty in the same study period for treatment of avascular
      corneal scars extending to the corneal periphery. All operations were performed
      by the same surgeon. Mean follow-up time for both study groups was 31.27 +/-
      21.54 and 32.0 +/- 19.4 months, respectively. RESULTS: In the autologous rotating
      keratoplasty group, visual acuity increased significantly (P = 0.03; Wilcoxon
      test) from 0.13 +/- 0.11 preoperatively to 0.29 +/- 0.16 postoperatively.
      Refractive astigmatism and keratometric astigmatism, respectively, increased (P =
      0.02) from 3.19 +/- 2.53 diopters and 3.20 +/- 2.24 diopters, respectively,
      preoperatively to 6.9 +/- 1.82 diopters and 9.55 +/- 4.32 diopters, respectively,
      postoperatively. Comparing the study groups, postoperative visual acuity was
      significantly lower (P = 0.01), and keratometric astigmatism (P = 0.003) and
      refractive astigmatism (P = 0.01) were significantly higher in the autologous
      rotating keratoplasty group than in the control group. CONCLUSIONS: Autologous
      ipsilateral rotating penetrating keratoplasty compared with homologous central
      penetrating keratoplasty is associated with a high postoperative refractive and
      keratometric astigmatism leading to a relatively low postoperative visual acuity.
      It suggests that, in normal clinical conditions when donor material is available
      and postoperative follow-up examinations can be performed, homologous central
      penetrating keratoplasty may be superior to autologous ipsilateral rotating
      keratoplasty.

PMID- 11292404
TI  - Epithelial pigment slide in contact lens wearers: a possible marker for contact
      lens-associated stress on corneal epithelium.
AB  - PURPOSE: To compare the incidence of epithelial pigment slide among wearers of
      various types of contact lenses. METHODS: Prospectively, we studied 432 eyes of
      432 patients. The patients were separated into 6 groups: hard contact lens (HCL)
      wearers (n = 166), conventional soft contact lens (CSCL) wearers (n = 30),
      extended disposable lens (EDCL) wearers (n = 46), frequent replacement SCL (FRCL)
      wearers (n = 60), daily disposable SCL (DDCL) wearers (n = 65), and normal
      controls (n = 65). The incidence of prominent pigment slide, defined as spike
      like epithelial opacities in the corneal limbus and longer than 1 mm from the
      base to the apex of the wedges-shaped process detected by slit-lamp examination,
      was compared in these 6 groups. The relationship between the incidence of
      prominent pigment slide and the length of contact lens wear was examined.
      RESULTS: The overall incidence of prominent pigment slide in the CSCL, EDCL, HCL,
      FRCL, DDCL, and normal groups was 63.3, 23.9, 13.9, 8.3, 7.7, and 4.6%,
      respectively. The incidence of prominent pigment slide in the CSCL and EDCL
      groups was significantly higher than that in the control group. A higher
      incidence of prominent pigment slide was correlated with longer wearing period in
      each group. CONCLUSIONS: The presence of epithelial pigment slide may be a marker
      for contact lens-associated stress to the corneal epithelium.

PMID- 11292405
TI  - Use of the HARK autorefractor in children.
AB  - PURPOSE: We investigated the reliability, accuracy, and repeatability of an
      autorefractor with the capability of over-refracting and measuring visual acuity
      for use in children in a prospective study. METHODS: Before and after
      cycloplegia, 68 children (mean +/- SD age, 10 +/- 3 years, range 5-16 years)
      underwent autorefraction twice with the HARK 599 Autorefractor (Humphrey
      Instruments Inc., San Leandro, CA), subjective over-refraction through the HARK
      autorefractor, and subjective refraction using a phoro-optometer. After
      cycloplegia, retinoscopy was performed. Results are reported for one eye (left)
      of each child. RESULTS: For 68 eyes of 68 children, before and after cycloplegia,
      correlation coefficients (R) for autorefraction reproducibility exceeded 0.95 for
      all comparisons of sphere and cylinder. R for spherical values for autorefraction
      vs. over-refraction was 0.93 and vs. subjective refraction 0.83 before
      cycloplegia and 0.94 and 0.97 after cycloplegia. Comparing values before and
      after cycloplegia, autorefraction, over-refraction, and subjective refraction,
      the data correlated > 0.81 for sphere and 0.75 to 0.87 for cylinder. Cycloplegic
      retinoscopy compared with autorefraction, over-refraction, and subjective
      refraction had R > 0.86 for sphere and cylinder for all comparisons except one.
      Cycloplegia increased the proportion of spherical equivalent values within 0.625
      D of the subjective refraction from 41 of 68 eyes (61%) for auto- and over
      refraction to 64 (94%) and 51 (75%) of the 68 eyes, respectively. A visual acuity
      of 20/30 or better was produced in 50 of 68 (73%) eyes with automated refraction
      before and after cycloplegia and in 62 (92%) with subjective refraction before
      cycloplegia and subjective refraction and retinoscopy after cycloplegia.
      Subjective over-refraction did not significantly improve the visual acuity.
      CONCLUSIONS: In children, HARK autorefraction improved in accuracy, when compared
      to subjective refraction, and the level of visual acuity improved after
      cycloplegia. Over-refraction through the instrument did not improve the results
      before or after cycloplegia.

PMID- 11292406
TI  - Visual loss in children with neurofibromatosis type 1 and optic pathway gliomas:
      relation to tumor location by magnetic resonance imaging.
AB  - PURPOSE: To examine the potential for visual acuity loss, and its relation to
      extent and location of optic pathway gliomas in a cohort of children with
      neurofibromatosis type 1 studied with magnetic resonance imaging. METHODS: We
      reviewed the neuro-ophthalmologic records and brain/orbital magnetic resonance
      imaging scans for 43 consecutive pediatric patients with neurofibromatosis type 1
      and optic pathway gliomas who were followed at the Children's Hospital of
      Philadelphia. The presence of visual loss, defined as abnormal visual acuity for
      age in one or both eyes, was determined. Optic pathway gliomas were classified by
      tumor extent and location according to involvement of the optic nerves, chiasm,
      and postchiasmal structures by magnetic resonance imaging. RESULTS: Involvement
      of the optic tracts and other postchiasmal structures at tumor diagnosis was
      associated with a significantly higher probability of visual acuity loss (P
      =.048, chi-square test). Visual loss was noted in 20 of 43 patients (47%) at a
      median age of 4 years; however, three patients developed visual acuity loss for
      the first time during adolescence. CONCLUSIONS: In pediatric patients with
      neurofibromatosis type 1 and optic pathway gliomas, the likelihood of visual loss
      is dependent on the extent and location of the tumor by magnetic resonance
      imaging and is particularly associated with involvement of postchiasmal
      structures. Furthermore, older age during childhood (adolescence) does not
      preclude the occurrence of visual loss. Close follow-up beyond the early
      childhood years, particularly for those with postchiasmal tumor, is recommended.

PMID- 11292407
TI  - Ultrasound biomicroscopic diagnosis of cyclitic membranes.
AB  - PURPOSE: To evaluate the utility of ultrasound biomicroscopy in imaging cyclitic
      membranes. METHODS: Patients with hypotony and suspected or known cyclitic
      membrane underwent ultrasound biomicroscopic examination. Histopathology of
      cyclitic membrane was correlated with ultrasound biomicroscopy in three cases.
      RESULTS: Six eyes of six patients were enrolled. Mean patient age was 62.2 +/-
      18.4 (SD) years. The mean intraocular pressure in the affected eye was 4.3 +/-
      3.4 mmHg. Three eyes were pseudophakic and three eyes were aphakic. All eyes had
      undergone two or more previous intraocular surgeries. Ultrasound biomicroscopy
      imaged the cyclitic membrane in all six eyes. Histopathology revealed
      fibroproliferative cyclitic membranes with associated inflammatory cells.
      CONCLUSION: Ultrasound biomicroscopy is useful in detecting the presence of those
      cyclitic membranes that may not be identified on clinical examination.

PMID- 11292408
TI  - Ocular features associated with anticardiolipin antibodies: a descriptive study.
AB  - PURPOSE: To evaluate ocular features in patients presenting with inflammation in
      the presence of anticardiolipin antibodies. METHODS: A descriptive study of 13
      patients presenting with idiopathic ocular inflammation involving anterior and
      posterior segment was performed. Patients were followed for a mean follow-up of
      22 months (range, 1 to 125). A comprehensive report of ocular involvement,
      including visual symptoms, visual acuity, clinical characteristics, funduscopic
      and fluorangiographic features, was reported. Systemic associated symptoms were
      analyzed. Laboratory investigations included anticardiolipin antibody titers and
      isotypes, presence of other autoantibodies, and markers of immune system
      activation. RESULTS: The most common ocular symptom at presentation was blurred
      vision (eight patients) followed by redness and pain(three patients) and visual
      loss(two patients). Anterior segment abnormalities, including iritis (eight
      patients) scleritis (two patients) and filamentary keratitis (one patient), were
      present in 76% of patients, whereas the most represented feature of posterior
      involvement was retinal vasculitis (60%) followed by vitritis (38%), retinal
      detachment (15%), posterior scleritis (7%), and central retinal artery occlusion
      (7%). All patients had abnormal titers of anticardiolipin antibodies,
      predominantly IgG isotype; six had markers of immune system activation.
      CONCLUSIONS: Although posterior pole disease is more commonly associated with
      anticardiolipin antibodies, the anterior segment can also be involved with a wide
      spectrum of features. Scleritis has never been previously described as associated
      with anticardiolipin antibodies. Systemic symptoms are frequently present in
      association with ocular disease.

PMID- 11292409
TI  - The ganciclovir implant plus oral ganciclovir versus parenteral cidofovir for the
      treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency
      syndrome: The Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial.
AB  - PURPOSE: To compare the regimen of the ganciclovir implant plus oral ganciclovir
      to one of intravenous cidofovir for the treatment of cytomegalovirus retinitis.
      METHODS: Sixty-one patients with acquired immunodeficiency syndrome and
      cytomegalovirus retinitis were randomized either to the regimen of the
      ganciclovir implant plus oral ganciclovir, 1 gm three times daily, or intravenous
      cidofovir, 5 mg/kg once weekly for two doses, followed by 5 mg/kg every other
      week. RESULTS: Mortality was similar between the two treatment groups. Mortality
      rates were 0.41 per person-year in patients assigned to the ganciclovir regimen
      and 0.49 per person-year in patients assigned to cidofovir (P =.59). Ocular
      outcomes were similar between the two groups. Retinitis progression occurred at a
      rate of 0.67 per person-year in the ganciclovir group and 0.71 per person-year in
      the cidofovir group (P =.72). A loss of visual acuity of 15 letters or more
      occurred at a rate of 0.78 per person-year in the ganciclovir group and 0.47 per
      person-year in the cidofovir group (P =.28). The rate of loss of visual field was
      7 degrees per month in the ganciclovir group and 2 degrees per month in the
      cidofovir group (P =.048). Vitreous hemorrhage was more common in the ganciclovir
      implant group (0.13 per person-year) than in the cidofovir group (no cases, P
      =.014), whereas uveitis appeared to be more common in the cidofovir group (0.35
      per person-year) than in the ganciclovir group (0.09 per person-year, P =.066).
      Nephrotoxicity (serum creatinine 1.6 mg/dL or greater) occurred at a rate of 0.18
      per person-year in the ganciclovir group and 0.48 per person-year in the
      cidofovir group (P =.10). CONCLUSIONS: Although the small number of patients in
      this study limits definitive interpretation, these data suggest that in the era
      of highly active antiretroviral therapy, the regimens of the ganciclovir implant
      plus oral ganciclovir and of intravenous cidofovir are similar for controlling
      cytomegalovirus retinitis and preventing visual loss but have different side
      effects.

PMID- 11292410
TI  - Intravitreal injection of crystalline cortisone as adjunctive treatment of
      proliferative diabetic retinopathy.
AB  - PURPOSE: To report the clinical outcome and complications of intravitreal
      injections of crystalline cortisone in patients undergoing pars plana vitrectomy
      for treatment of proliferative diabetic retinopathy. METHODS: The prospective,
      interventional case series study included 29 consecutive patients (29 eyes) who
      underwent pars plana vitrectomy for treatment of complicated proliferative
      diabetic retinopathy associated with central retinal traction detachment. All
      patients received an intravitreal injection of 15 to 20 mg of crystalline
      triamcinolone acetonide at the end of surgery, and were operated on by the same
      surgeon. Mean follow-up time was 1.4 +/- 1.1 months (median, 1 month; range, 0.30
      to 4.9 months). RESULTS: At the end of the follow-up period, the retina was
      attached in 26 of the 29 patients (89.7%). In three of the 29 patients (10.3%), a
      retinal redetachment had occurred. None of the patients developed iris
      neovascularization, and the iris neovascularization, present preoperatively in 12
      patients, slightly to markedly regressed in all 12 patients. Preoperative and
      postoperative intraocular pressure values (P =.72) and blood glucose measurements
      did not vary significantly. A pseudohypopyon consisting of cortisone crystals in
      the inferior anterior chamber angle was detected in one patient and resolved
      spontaneously within 4 days. CONCLUSIONS: The present clinical study suggests
      that intravitreal injection of crystalline cortisone with most of the vehicle
      removed seems to be well tolerated by eyes undergoing pars plana vitrectomy for
      treatment of complicated diabetic proliferative retinopathy. In view of the
      antiphlogistic and antiproliferative effect of cortisone, future randomized
      clinical trials may be indicated to investigate further the role of intravitreal
      injection of crystalline cortisone in the treatment of proliferative diabetic
      retinopathy.

PMID- 11292411
TI  - Retinal pigment epithelial cell transplantation after subfoveal membranectomy in
      age-related macular degeneration: clinicopathologic correlation.
AB  - PURPOSE: To report the histopathology after retinal pigment epithelial cell
      transplantation and subfoveal membranectomy in age-related macular degeneration.
      METHODS: An 85-year-old white woman with bilateral choroidal neovascularization
      underwent subfoveal membranectomy combined with transplantation of a sheet of
      human adult retinal pigment epithelium (retinal pigment epithelium) under the
      foveal center in the right eye. The patient was immunosuppressed postoperatively
      with prednisone, cyclosporine, and azathioprine. The patient died from congestive
      heart failure 114 days after surgery. RESULTS: A patch of hyperpigmentation was
      visible at the transplant site under the foveola after surgery. Mound-like
      clusters of individual round, large densely pigmented cells were present in the
      subretinal space and outer retina in this area. There was loss of the
      photoreceptor outer segments and native retinal pigment epithelium in the center
      of the transplant bed, with disruption of the outer nuclear layer predominantly
      over regions of multilayered pigmented cells. Cystic spaces were present in the
      inner and outer retina. A residual intra-Bruchs membrane component of the
      original choroidal neovascular complex was present under the transplant site.
      CONCLUSIONS: The transplant site contained clusters of round, pigmented cells
      that did not form a uniform monolayer in most areas. The morphology at the
      transplant site is consistent with the lack of visual improvement seen after
      surgery in this patient.

PMID- 11292412
TI  - Effect of Ca(2+)-free and Mg(2+)-free BSS Plus solution on the retinal pigment
      epithelium and retina in rabbits.
AB  - PURPOSE: To determine whether intravitreal irrigation with Ca(2+)-free and Mg(2+)
      free BSS Plus (Alcon Laboratory, Fort Worth, Texas) solution alters the
      adhesiveness between the retinal pigment epithelium and the retina of rabbits.
      METHODS: Thirty-four eyes of 34 Dutch pigmented rabbits underwent lensectomy and
      vitrectomy. Subsequently, the vitreous cavity of 24 eyes was irrigated with
      Ca(2+)-free and Mg(2+)-free BSS Plus solution for 10 or 20 minutes. The other 10
      eyes were irrigated with BSS Plus solution for 20 minutes as controls. To
      determine the adhesiveness between the retinal pigment epithelium and retina, a
      retinal detachment was produced in 12 of the 34 eyes. The apical surface of the
      retinal pigment epithelium and the photoreceptor outer segments were examined by
      scanning electron microscopy. Retinal physiology was assessed by
      electroretinography and retinal morphology by light microscopy. RESULTS: After
      retinal detachment was produced, the number of cone sheaths on the apical surface
      of the retinal pigment epithelium after irrigation with Ca(2+)-free and Mg(2+)
      free BSS Plus solution for 20 minutes (33 +/- 15, mean +/- SD) was significantly
      less than the number of cone sheaths on the apical surface of the retinal pigment
      epithelium of eyes after irrigation with BSS Plus solution for 20 minutes (120 +/
      50) or the number of cone sheaths on the apical surface of the retinal pigment
      epithelium of eyes after 10 minutes of irrigation with Ca(2+)-free and Mg(2+)
      free BSS Plus solution (115 +/- 49; P =.02). The b-wave amplitudes in the eyes
      irrigated with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes were
      depressed compared with the b-waves in eyes irrigated with BSS Plus solution for
      20 minutes on the first postoperative day (P =.03). After the third postoperative
      day, there was no significant difference in the b-waves (P >.06). Light
      microscopy demonstrated no morphologic abnormalities after the use of both
      solutions. CONCLUSIONS: Intravitreal irrigation with Ca(2+)-free and Mg(2+)-free
      BSS Plus solution for 20 minutes altered the adhesion between the retinal pigment
      epithelium microvilli and retinal outer segments and made the creation of retinal
      detachment less traumatic. These results suggest that Ca(2+)-free and Mg(2+)-free
      BSS Plus solution may be of clinical value for the creation of an intentional
      retinal detachment for foveal translocation surgery.

PMID- 11292413
TI  - On- and off-responses of the photopic electroretinograms in X-linked juvenile
      retinoschisis.
AB  - PURPOSE: To examine the physiologic condition of the middle retinal layer of
      patients with X-linked juvenile retinoschisis (xlRS) by studying the on- and off
      responses of the photopic electroretinograms (ERGs). METHODS: Eleven unrelated
      Japanese men (mean age; 24.9 +/- 7.6 years) who were clinically diagnosed with
      xlRS and molecularly confirmed as having XLRS1 mutations were investigated. For
      the photopic ERGs, the a-, b- and d-wave amplitudes elicited by long duration
      stimuli were recorded, and the responses from the xlRS patients were compared to
      those recorded from normal subjects (n = 14, mean age, 27.5 +/- 4.5 years). We
      also examined the relationship between the photopic ERG responses and the
      genotype. RESULTS: No significant difference was found between the a- and d-wave
      amplitudes in the xlRS patients (34.2 +/- 8.7 microV, 52.5 +/- 10.4 microV,
      respectively), and those in normal subjects (40.4 +/- 10.3 microV, 44.7 +/- 6.3
      microV, respectively). The mean b-wave amplitude in the xlRS patients was
      significantly smaller (10.5 +/- 7.7 microV) than the mean of normal subjects
      (46.4 +/- 10.2 microV) (P < 0.0001). No significant correlation was found between
      the ERG responses and the locus of the mutation. CONCLUSION: The photopic ERG
      demonstrated considerable impairment of the on-pathway arising from an
      abnormality of the on-bipolar cells or possibly secondary to Muller cell
      abnormality in xlRS.

PMID- 11292414
TI  - Autosomal dominant inheritance of a negative electroretinogram phenotype in three
      generations.
AB  - PURPOSE: We report an abnormal electroretinogram with a negative configuration in
      a child who presented with moderate myopia, nystagmus, and visual developmental
      delay. We investigated the electroretinogram and explored the possibility of a
      metabotropic glutamate receptor subtype 6 mutation in six family members spanning
      four generations. METHODS: Case report and family study: Complete eye
      examinations and Ganzfeld electroretinograms were recorded from the maternal
      great-grandmother, maternal grandmother, mother, uncle, and sibling of the 7
      month-old female proband. The electroretinogram was repeated in the proband at 17
      months of age. Dark adaptometry was performed in all adult subjects. Fundus
      photographs and visual field examinations were administered to the grandmother
      and mother. The metabotropic glutamate receptor subtype 6 gene was amplified and
      sequenced in all affected subjects. RESULTS: The proband had a negative
      electroretinogram and a normal fundus. The maternal grandmother, uncle, and
      mother had an abnormal electroretinogram identical to the proband yet had no
      visual complaints. The ophthalmology examinations in the adult subjects were
      normal, and subsequent examination of the proband at 17 months, 5 years, and 6.5
      years of age showed no changes in the fundus or refractive error. Her nystagmus
      resolved by 5 years of age. Rod threshold and visual fields were normal in the
      affected adult subjects. No mutation in the metabotropic glutamate receptor
      subtype 6 gene was found. CONCLUSIONS: In this family, a negative
      electroretinogram was not associated with decreased rod threshold, visual acuity
      loss, visual field loss, muscle disease, or metabotropic glutamate receptor
      subtype 6 mutation. Additional study will be required to understand the nature of
      the negative electroretinogram phenotype in this family.

PMID- 11292415
TI  - Randomized clinical trials in ophthalmology in 2001: twenty-fifth anniversary of
      the first publication from the Diabetic Retinopathy Study.

PMID- 11292416
TI  - Late-onset traumatic laser in situ keratomileusis (LASIK) flap dehiscence.
AB  - PURPOSE: To report a case of laser in situ keratomileusis (LASIK) flap dehiscence
      following focal trauma six months after uneventful refractive surgery. METHODS:
      Case report. A 37 year old man was seen one day after a tree branch snapped
      tangentially against his left cornea causing a dehiscence of his LASIK flap.
      RESULTS: The flap was repositioned after treating the exposed flap stroma with a
      50:50 mixture of distilled water and balanced salt solution. The patient regained
      20/20 uncorrected visual acuity. CONCLUSIONS: Patients should be informed about
      the potential for traumatic flap dehiscence following LASIK surgery and advised
      to wear eye protection when appropriate. Due to minimal wound healing except at
      the edges of the flap, corneal flap dehiscence may occur months or years after
      uneventful LASIK.

PMID- 11292417
TI  - Experimental laser-assisted in situ keratomileusis induces the reactivation of
      latent herpes simplex virus.
AB  - PURPOSE: We determined whether laser-assisted in situ keratomileusis acts as a
      trigger for the reactivation and ocular shedding of herpes simplex virus type-1
      in a rabbit latency model. METHODS: Herpes simplex virus type-1 latently infected
      rabbits were divided into three treatment groups: Group I received surface
      excimer laser ablation in both eyes (positive control), Group II received laser
      assisted in situ keratomileusis in both eyes, and Group III received no treatment
      (negative control). Eyes were cultured daily for 10 days to determine herpes
      simplex virus type-1 reactivation. RESULTS: The number of herpes simplex virus
      type-1 positive eye cultures and total herpes simplex virus type-1 shedding days
      were significantly greater after surface excimer laser ablation and laser
      assisted in situ keratomileusis compared with the untreated control group (P <
      0.002 and P < 0.000001, respectively). CONCLUSION: Laser-assisted in situ
      keratomileusis as well as surface excimer laser ablation act as a trigger for the
      reactivation of herpes simplex virus type-1 in the rabbit latency model.

PMID- 11292418
TI  - Microkeratome-induced reduction of astigmatism after penetrating keratoplasty.
AB  - PURPOSE: To report the reduction in postpenetrating keratoplasty astigmatism with
      the use of the microkeratome to create a lamellar corneal flap as the first stage
      in a two-step laser in situ keratomileusis. METHODS: The hansatome microkeratome
      was used to create a lamellar corneal flap in a 24-year-old man with a net
      corneal astigmatism of 7.3 diopters, 2 years after penetrating keratoplasty. No
      laser ablation was performed. RESULTS: The net corneal astigmatism reduced to 3.9
      diopters at 1 month and 2.3 diopters at 3 months of follow-up, without any laser
      ablation. CONCLUSION: Laser in situ keratomileusis may be performed as a two
      stage procedure, because the lamellar corneal flap alone may reduce
      postpenetrating keratoplasty astigmatism.

PMID- 11292419
TI  - Acanthamoeba keratitis associated with fungal keratitis.
AB  - PURPOSE: To report fungal infection complicating Acanthamoeba keratitis. METHODS:
      Case report. A 45-year-old woman with contact lens-related bilateral Acanthamoeba
      keratitis developed corneal ulcer, corneal perforation, and mature cataract in
      the left eye, which was managed by penetrating keratoplasty, lensectomy, and
      vitrectomy. RESULTS: Histopathologic examination of the keratoplasty specimen
      from the left eye revealed extensive lamellar stromal necrosis with the
      coexistence of both empty cysts and branching hyphae. Cultures from the
      keratoplasty specimen grew Scedosporium apiospermum. CONCLUSION: Keratomycosis
      caused by S. apiospermum may complicate protracted Acanthamoeba keratitis.

PMID- 11292420
TI  - The Taa1 restriction enzyme provides a simple means to identify the Q368STOP
      mutation of the myocilin gene in primary open angle glaucoma.
AB  - PURPOSE: To identify a rapid and reliable method to detect the Glutamine 368 STOP
      (Q368STOP) disease-predisposing allele of the myocilin gene associated with adult
      onset, primary, open-angle glaucoma. METHODS: Individuals with the Q368STOP
      mutation of the myocilin gene were identified from a cohort of primary open-angle
      glaucoma patients from Tasmania and subjected to Taa1 restriction digestion.
      RESULTS: In the Tasmanian family presented, screening with the Taa1 restriction
      enzyme successfully confirmed identification of all individuals with the Q368STOP
      mutation. CONCLUSIONS: The use of the Taa1 restriction enzyme offers a relatively
      simple, rapid, and reproducible technique that could be applied to detect the
      Q368STOP mutation of the myocilin gene.

PMID- 11292421
TI  - Vitreous opacities affect scanning laser polarimetry measurements.
AB  - PURPOSE: To assess the effect of vitreous opacities on retinal nerve fiber layer
      retardation measurements obtained during scanning laser polarimetry. METHODS:
      Scanning laser polarimetry was performed in two eyes of two patients with
      vitreous opacities. RESULTS: The presence of a vitreous opacity within the
      measurement ellipse during scanning caused a marked, localized increase in
      polarization in the area of the opacity. This falsely increased the value
      obtained for the mean retinal nerve fiber layer thickness. Retinal nerve fiber
      layer thickness values were reduced when the opacity was not incorporated into
      the measurement ellipse. CONCLUSION: Artifact introduced by the presence of
      vitreous opacities can affect scanning laser polarimetry measurement reliability.

PMID- 11292422
TI  - Vitrectomy for pars planitis complicated by vitreous hemorrhage: visual outcome
      and long-term follow-up.
AB  - PURPOSE: To characterize the visual results of vitrectomy for nonclearing
      vitreous hemorrhage in pars planitis. METHODS: Case series. RESULTS: All six eyes
      (100%) had a visual acuity of 20/200 or less preoperatively. Postoperatively,
      five eyes (83%) improved to a final visual acuity of better than 20/30, and one
      eye improved to 20/100. The poorer vision of the latter patient was attributed to
      cystoid macular edema. Postoperative follow-up range was from 1.3 to 9 years
      (mean, 4.2 years). CONCLUSION: A substantial long-term benefit is seen in
      patients with pars planitis treated with vitrectomy for nonclearing vitreous
      hemorrhage. A larger case series will be needed to confirm whether such excellent
      outcomes can be expected.

PMID- 11292423
TI  - Echographic evaluation of a patient with diabetes and dense vitreous hemorrhage:
      an avulsed retinal vessel may mimic a tractional retinal detachment.
AB  - PURPOSE: To report that an avulsed retinal vessel may appear as a tractional
      retinal detachment on echographic evaluation. METHODS: Case report. RESULTS: A 57
      year-old diabetic woman presented with a nonclearing vitreous hemorrhage of 2
      months duration in the left eye. Echography was consistent with a localized
      tractional retinal detachment on longitudinal sections; transverse sections
      demonstrated a pinpoint opacity in the vitreous cavity. Intraoperatively, an
      avulsed retinal vessel was noted in the area of echographic abnormality.
      CONCLUSION: An avulsed retinal vessel may mimic tractional retinal detachment on
      echography. Although trained ophthalmic echographers routinely perform both
      longitudinal and transverse sections during an echographic evaluation, less
      skilled observers must be aware of the importance of performing both longitudinal
      and transverse sections for accurate echographic diagnosis.

PMID- 11292424
TI  - Malattia leventinese presenting with subretinal neovascular membrane and
      hemorrhage.
AB  - PURPOSE: To report a case of malattia leventinese involving subretinal
      hemorrhage. METHODS: Case report. RESULTS: Two weeks after initial presentation,
      the visual acuity of this 34-year-old man decreased to LE: 20/100. Funduscopic
      evaluation revealed a subretinal hemorrhage involving the center of the foveal in
      the left eye that was interpreted as secondary to a neovascular membrane on
      fluorescein angiography. The patient did well after the removal of the submacular
      material by pars plana vitrectomy. CONCLUSION: Patients with malattia leventinese
      may occasionally present with submacular hemorrhage. Prompt diagnosis and
      intervention may enhance the patient's chance for visual improvement.

PMID- 11292425
TI  - Retinal pigment epithelial tear after photodynamic therapy for choroidal
      neovascularization.
AB  - PURPOSE: To report a case of retinal pigment epithelial tear after photodynamic
      therapy for choroidal neovascularization. METHODS: Case report. A 74-year-old
      woman with exudative age-related macular degeneration and classic subfoveal
      choroidal neovascularization RE underwent photodynamic therapy with verteporfin.
      RESULTS: Ophthalmoscopy and fluorescein angiography RE disclosed a retinal
      pigment epithelial tear in the area of photodynamic therapy. CONCLUSION: This
      case presents the first report of a retinal pigment epithelial tear after
      photodynamic therapy with verteporfin for subfoveal choroidal neovascularization
      in age-related macular degeneration.

PMID- 11292426
TI  - Globe perforation associated with subtenon's anesthesia.
AB  - PURPOSE: To report a case of globe perforation while initiating posterior
      subtenon's anesthesia. METHODS: Case report. A 40-year-old man with a history of
      retinal detachment in both eyes presented for repair of a second retinal
      detachment in the LE. RESULTS: Upon dissecting a space beneath the Tenon capsule
      with scissors, the globe was perforated. CONCLUSION: In patients with prior
      ophthalmologic surgery, thinned sclera, or excess scar tissue, increased caution
      should be employed during initiation of sub-Tenon anesthesia or an alternative
      method should be used.

PMID- 11292427
TI  - Bilateral breast metastases from choroidal melanoma.
AB  - PURPOSE: To report an unusual case of solitary sequential bilateral breast
      metastases from choroidal melanoma. METHOD: Case report. RESULTS: A 48-year-old
      woman with a large choroidal melanoma in the left eye was treated with Iodine-125
      brachytherapy and responded satisfactorily with decrease in tumor thickness.
      Thirty-seven months after treatment, she developed a solitary, circumscribed
      melanoma metastasis to the right breast, and 54 months after treatment, a similar
      metastasis was detected in her left breast. Both breast tumors were managed with
      lumpectomy. Systemic examination including magnetic resonance imaging of abdomen,
      chest, and head have been performed regularly and have been normal. At 61 months
      after treatment, the patient has no clinical evidence of metastatic disease
      elsewhere. CONCLUSIONS: Uveal melanoma rarely metastasizes to breast tissue. A
      breast nodule in a patient with a history of uveal melanoma is most likely a
      primary breast tumor but may rarely represent a metastasis from uveal melanoma.

PMID- 11292428
TI  - Horner's syndrome and dissection of the internal carotid artery after
      chiropractic manipulation of the neck.
AB  - PURPOSE: To report a case of Horner's syndrome and dissection of the internal
      carotid artery after chiropractic manipulation of the neck. METHODS: Case report.
      A 44-year-old woman with no prior ocular or vascular history presented with
      severe right-sided head and neck pain, ptosis, and miosis following chiropractic
      treatment for a strained right shoulder muscle. RESULTS: Magnetic resonance
      angiography of the neck and brain revealed a dissection of the right internal
      carotid artery as well as a suggestion of subtle dissection in the right
      vertebral artery. No significant brain abnormalities were noted on magnetic
      resonance imaging. Pharmacological testing was consistent with preganglionic
      oculosympathetic damage. CONCLUSION: Acute, painful Horner's syndrome as a
      manifestation of vascular dissection may be associated with chiropractic
      manipulation of the neck.

PMID- 11292429
TI  - A case of multiple sclerosis with granulomatous uveitis in Japan--use of the
      antilipoarabinomannan (LAM)-B test in differential diagnosis.
AB  - PURPOSE: To report a patient with multiple sclerosis and associated with
      granulomatous uveitis, and how anti-lipoarabinomannan (LAM)-B antibody can play a
      key role in differential diagnosis. METHODS: Case report. RESULTS: A 35-year-old
      Japanese woman with multiple sclerosis, diagnosed 3 years ago, presented with
      blurred vision in her left eye. Ophthalmological examinations revealed
      granulomatous iridocyclitis in her left eye and retinal periphlebitis in both
      eyes. The diagnosis of tuberculosis was suspected because of a positive
      tuberculin skin test. However, a further examination by an anti-LAM-B antibody
      test excluded active tuberculosis. Her clinical findings were thought most likely
      to be caused by multiple sclerosis and treated with corticosteroids. CONCLUSION:
      We should consider the possibility of multiple sclerosis as the underlying origin
      in patients with granulomatous uveitis. A measurement of anti-LAM-B antibody
      titer may be useful in the differential diagnosis of granulomatous uveitis.

PMID- 11292430
TI  - Extraocular muscle cysticercosis presenting as Brown syndrome.
AB  - PURPOSE: Report of a case of acquired Brown syndrome caused by infestation of the
      superior oblique muscle by Cysticercus cellulosae. METHOD: Case seen in a
      referral practice. A 20-year-old man presented with recurrent attacks of
      conjunctivitis and diplopia in upgaze. Clinical examination of ocular motility
      established a diagnosis of acquired Brown syndrome of the right eye. Computed
      tomography of the right orbit unequivocally established the diagnosis of superior
      oblique muscle cysticercosis. The patient was started on systemic steroids and
      albendazole in the prescribed doses for a month. RESULT: Serial computed
      tomography scans of the orbit revealed resolution of the cystic lesion after a
      month. Clinically, although there was restoration of ocular motility in upgaze,
      mild restriction of movement of the right eye in levoelevation persisted.
      However, the patient was symptomatically better with amelioration of the
      recurrent conjunctivitis and diplopia in primary gaze. CONCLUSION: Extraocular
      muscle cysticercosis should be considered in the differential diagnosis of
      acquired motility disorder. The presentation of extraocular muscle cysticercosis
      as an acquired Brown syndrome is unusual. Response to medical therapy was
      satisfactory.

PMID- 11292443
TI  - Enrichment of neuronal and glial connexins in the postsynaptic density
      subcellular fraction of rat brain.
AB  - The similar dense, protein-rich and detergent-resistant characteristics of
      postsynaptic densities (PSDs) and gap junctions led us to investigate the
      distribution of gap junctions and their constituent connexins in CNS subcellular
      fractions containing PSDs. Western blot analysis showed these fractions to be
      enriched in both neuronal and glial connexins, namely, connexin26, connexin30,
      connexin36 and connexin43. Connexins were retained in these fractions after
      treatment with n-lauroyl sarcosine to remove loosely associated proteins.
      Confocal double immunofluorescence confirmed the presence of connexins in PSD
      fractions and showed a near total co-localization of glial connexin30 and
      connexin43, demonstrating preservation of inter-connexin relationships that have
      been observed in vivo. In contrast, none of the connexins were co-localized with
      the PSD structural protein PSD-95, indicating their lack of direct association
      with PSDs. These results show that PSD preparations contain significant levels of
      connexin proteins, which appear to remain assembled as gap junctions. Thus,
      protocols used to isolate PSDs may serve as a basis for development of methods to
      isolate CNS gap junctions, which would aid biochemical identification of
      regulatory and structural proteins associated with these structures.

PMID- 11292444
TI  - Neurons in the lamina terminalis which project polysynaptically to the kidney
      express angiotensin AT1A receptor.
AB  - The retrograde transynaptic transport of pseudorabies virus was used in
      conjunction with hybridisation histochemistry for the angiotensin II AT1A
      receptor, to characterise neurons in the lamina terminalis projecting to the
      kidney. These data demonstrate that some neurons in the lamina terminalis, that
      project polysynaptically to the kidney, may be responsive to angiotensin II.

PMID- 11292445
TI  - Cataleptic effect of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice:
      modulation by serotonergic agents.
AB  - The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) induced
      catalepsy in mice is modified by dopaminergic, adenosinergic and GABAergic
      agents. In light of serotonergic agents being implicated in antipsychotic-induced
      catalepsy and their ability to increase brain neurosteroid content, the present
      study was undertaken to investigate the effect of various 5-HT agents on
      catalepsy induced by 3alpha,5alpha-THP in mice. Pretreatment with selective
      serotonin reuptake inhibitor, fluoxetine (5 mg/kg, i.p.), 5-HT releaser,
      fenfluramine (10 mg/kg, i.p.), 5-HT(1A) receptor agonist, 8-OH-DPAT (0.3 mg/kg,
      s.c.), 5-HT1B/1C receptor agonist, TFMPP (3 mg/kg, i.p.), 5-HT2A/1C receptor
      agonist, DOI (1.5 mg/kg, s.c.) and 5-HT3 agonist, 2-methylserotonin (5 mg/kg,
      i.p.) potentiated the catalepsy induced by exogenous administration of
      3alpha,5alpha-THP. Furthermore, FGIN 1-27, an MDR agonist that increases
      endogenous content of 3alpha,5alpha-THP although per se failed to exhibit any
      cataleptic effect but enhanced the cataleptic response in combination with these
      serotonergic agents. The potentiating action of 5-HT1A, 5-HT2A/1C or 5-HT3
      receptor agonist on 3alpha,5alpha-THP induced catalepsy was not blocked by prior
      administration of sub-effective dose (1 mg/kg, s.c.) of their respective receptor
      antagonists pindolol, ritanserin or ondansetron or by pretreatment with
      serotonergic neurotoxin 5,7-DHT (100 microg/mouse, i.c.v.). However this effect
      of different serotonergic agents was antagonized by the GABA(A) receptor
      antagonist, bicuculline (1 mg/kg, i.p.) or the 3alpha-hydroxysteroid
      oxidoreductase enzyme inhibitor, indomethacin (5 mg/kg, i.p.). The 5-HT agents
      enhance neurosteroid-induced catalepsy by increasing GABAergic tone, likely as a
      consequence of increased brain content of 3alpha,5alpha-THP.

PMID- 11292446
TI  - Dose-dependent protective effects of apomorphine against methamphetamine-induced
      nigrostriatal damage.
AB  - (R)-apomorphine is a non-selective dopamine (DA) agonist which is used in the
      treatment of Parkinson's disease. In addition to symptomatic effects, apomorphine
      exerts a neuroprotective activity in specific experimental models. For instance,
      apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine
      does not seem to be related to its dopamine (DA) agonist properties, instead it
      appears to be grounded on the antioxidant and the free radical scavenging effects
      of the compound. In this study, we sought to determine whether apomorphine
      protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10
      mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart)
      induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in
      the rat striatum. These protective effects are neither due to a decrease in the
      amount of striatal methamphetamine nor to hypothermia as indicated by measurement
      of striatal methamphetamine and body temperature at different time intervals
      after drug administration. The effects of apomorphine were neither opposite to,
      nor reversed by the DA antagonist haloperidol despite no decrease in body
      temperature was observed when apomorphine was given in combination with
      haloperidol. The present data are in line with recent studies suggesting a DA
      receptor-independent neuroprotective effect of apomorphine on DA neurons and call
      for further studies aimed at evaluating potential neuroprotective effects of
      apomorphine in Parkinson's disease.

PMID- 11292447
TI  - Expression of brain specific chondroitin sulfate proteoglycans, neurocan and
      phosphacan, in the developing and adult hippocampus of Ihara's epileptic rats.
AB  - Ihara's epileptic rats (IER) is an animal model of temporal lobe epilepsy with
      mycrodysgenesis, that exhibit abnormal migration of hippocampal neurons and
      recurrent spontaneous seizures. As an attempt to elucidate the roles of
      extracellular matrix molecules in the epileptogenecity and mossy fiber sprouting,
      immunohistochemical localization of brain specific chondroitin sulfate
      proteoglycans (CSPGs), neurocan and phosphacan, was examined in the hippocampus
      of postnatal IER and Sprague-Dawley (SD) rats using monoclonal antibodies 1G2
      against neurocan and 6B4 against phosphacan. There was no difference in the
      expression of these two CSPGs between IER and SD rats in the 1st postnatal week.
      However, the expression of neurocan was poor in the hippocampus of IER in the 2nd
      and 3rd weeks whereas intense labeling of neurocan was present throughout the
      hippocampus of SD rats. Labeling of neurocan was almost absent in the
      hippocampus, while phosphacan was diffusely expressed in the stratum oriens and
      radiatum of Ammon's horn, and in the hilus and inner one-third molecular layer of
      the dentate gyrus at the 2nd month after birth. There was no difference in the
      expression of neurocan and phosphacan between IER and SD rats at the 2nd month
      after birth. By contrast, phosphacan was reduced in the inner molecular layer of
      the dentate gyrus in 8-month-old IER, while neurocan was reexpressed in the outer
      molecular layer and hilus in 3- and 8-month-old IER. It was suggested that the
      insufficient expression of neurocan may affect the development of neuronal
      organization in the hippocampus, and that the remodeling of extracellular matrix
      in the dentate gyrus may contribute to the mossy fiber sprouting into the inner
      molecular layer.

PMID- 11292448
TI  - Rapid expression of neuronal and inducible nitric oxide synthases during post
      ischemic reperfusion in rat brain.
AB  - OBJECTIVE: To determine whether neuronal and inducible nitric oxide synthase
      (nNOS and iNOS) isoforms are expressed within cortical neurons during early
      reperfusion after focal cerebral ischemia. METHODS: Male spontaneously
      hypertensive rats underwent occlusion of the left middle cerebral artery for 2 h.
      Coronal brain sections with normal and ischemic cortex were obtained after 15 min
      or 1, 6 or 24 h of reperfusion. Immunohistochemical and double-label
      immunofluorescent techniques were used to confirm cellular identity and localize
      nNOS and iNOS. RESULTS: Immunoreactive nNOS was identified within isolated
      neurons in layer V of normal cortex. However, the number of nNOS-immunoreactive
      neurons in ischemic cortex rose markedly at 15 min and persisted for 24 h (P< or
      =0.001 at each time point when compared to normal cortex). Cells that were
      immunoreactive for nNOS appeared in perivascular clusters within ischemic brain
      at all sampling times. Immunoreactive iNOS was also expressed within neurons in
      ischemic cortex, peaking after 15 min of reperfusion (P< or =0.01). Although nNOS
      immunoreactive neurons were observed in random numbers within normal tissue
      throughout reperfusion, iNOS-immunoreactive neurons increased steadily in the
      same region (P< or =0.05). CONCLUSIONS: Ischemic neurons become immunoreactive
      for both nNOS and iNOS during early reperfusion. Expression of iNOS
      immunoreactivity in unaffected neurons may reflect transcription of immediate
      early genes in response to stimulatory neurotransmission from ischemic cortex.

PMID- 11292449
TI  - Changes of the cholinergic input to the superior colliculus following enucleation
      in neonatal and adult rats.
AB  - The effects of neonatal and adult enucleation on the adult pattern of cholinergic
      inputs to the rat superior colliculus (SC) was analysed. In the superficial
      layers immunohistochemical labelling revealed that choline acetyltransferase
      (ChAT) was predominantly confined to single boutons which were almost
      continuously distributed throughout the rostrocaudal and lateromedial axes. In
      these layers a higher density of boutons was observed in the stratum zonale (SZ)
      and lower stratum griseum superficiale (SGSl) than in the upper stratum griseum
      superficiale (SGS(u)) and stratum opticum (SO). In intermediate collicular layers
      ChAT-immunostaining was mainly found in axonal profiles which were arranged in a
      patchy fashion. Neonatal enucleation caused a drastic increase in bouton density
      in the SZ, SGS(u) and SGSl. The density of boutons was particularly high in the
      SGS(u), giving the appearance of an almost homogeneous distribution of boutons
      from the collicular surface down to the upper limit of SO. Visual
      deafferentiation at the adult stage was followed by an increase in the bouton
      density exclusively in the SZ. Neonatal enucleation produced a dorsoventral
      enlargement of the region containing patches of ChAT staining which was slightly
      greater following adult deafferentiation. The results described here show that
      after visual deafferentiation an increase in ChAT innervation to superficial and
      intermediate collicular layers occurs, providing new information regarding
      plasticity in the visual system. In view of previous data on cholinergic function
      in the central nervous system, such an increase could compensate for the loss of
      retinal excitatory input by facilitating neuronal responses in the SC.

PMID- 11292450
TI  - Perinatal exposure to environmental tobacco smoke induces adenylyl cyclase and
      alters receptor-mediated cell signaling in brain and heart of neonatal rats.
AB  - Perinatal exposure to environmental tobacco smoke (ETS) has adverse effects on
      neurobehavioral development. In the current study, rats were exposed to ETS
      during gestation, during the early neonatal period, or both. Brains and hearts
      were examined for alterations in adenylyl cyclase (AC) activity and for changes
      in beta-adrenergic and m2-muscarinic cholinergic receptors and their linkage to
      AC. ETS exposure elicited induction of total AC activity as monitored with the
      direct enzymatic stimulant, forskolin. In the brain, the specific coupling of
      beta-adrenergic receptors to AC was inhibited in the ETS groups, despite a normal
      complement of beta-receptor binding sites. In the heart, ETS evoked a decrease in
      m2-receptor expression. In both tissues, the effects of postnatal ETS, mimicking
      passive smoking, were equivalent to (AC) or greater than (m2-receptors) those
      seen with prenatal ETS mimicking active smoking; the effects of combined prenatal
      and postnatal exposure were equivalent to those seen with postnatal exposure
      alone. These data indicate that ETS exposure evokes changes in cell signaling
      that recapitulate those caused by developmental nicotine treatment. Since
      alterations in AC signaling are known to affect cardiorespiratory function, the
      present results provide a mechanistic link reinforcing the participation of ETS
      exposure, including postnatal ETS, in disturbances culminating in events like
      Sudden Infant Death Syndrome.

PMID- 11292451
TI  - Differential effects of pentylenetetrazol-kindling on long-term potentiation of
      population excitatory postsynaptic potentials and population spikes in the CA1
      region of rat hippocampus.
AB  - The effects of pentylenetetrazol-kindling on synaptic transmission and the
      effectiveness of &theta; pattern primed-bursts (PBs) for the induction of long
      term potentiation (LTP) of population excitatory postsynaptic potentials and
      population spikes were investigated in hippocampal CA1 of pentylenetetrazol
      kindled rats. Experiments were carried out in the control and kindled animals at
      two post-kindling periods, i.e., 48-144 h (early phase) and 30-33 days (long
      lasting phase). Field potentials (population excitatory postsynaptic potentials,
      pEPSPs; and population spikes, PSs) were recorded at the stratum radiatum and the
      stratum pyramidale following stimulation of the stratum fibers, respectively. PBs
      were delivered to stratum fibers and PB potentiation was assessed. The results
      showed that 48-144 h after kindling there was no significant difference for pEPSP
      slope and PS amplitude between two groups. But at 30-33 days after kindling, the
      pEPSP slope in the stratum radiatum of kindled animals decreased, whereas the
      amplitude of PSs increased compared to those of controls. Shortly after kindling,
      control animals had normal LTP of pEPSP slope and PS amplitude in response to
      PBs, but kindled rats lack LTP of pEPSP slope and PBs induced LTP of PS amplitude
      in most of kindled animals. In 30-33 days after kindling, PB potentiation was not
      observed in the stratum radiatum of kindled animals but PBs induced LTP of PS
      amplitude, which was significantly greater than that of control animals. The
      effect is compatible with the hypothesis, which postulates kindling-associated
      functional deficit in hippocampus, especially CA1, as an explanation for the
      behavioral deficits seen with the kindling model of epilepsy.

PMID- 11292452
TI  - The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates
      NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures.
AB  - The potential toxic effects of the metabotropic glutamate receptor agonist
      (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions
      with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain
      slice cultures, using densitometric measurements of the cellular uptake of
      propidium iodide (PI) to quantify neuronal degeneration. Cultures exposed to
      ACPD, showed a concentration (2-5 mM) and time (1-4 days) dependent increase in
      PI uptake in CA1, CA3 and dentate subfields after 24 h and 48 h of exposure, with
      CA1 pyramidal cells being most sensitive. The neurodegeneration induced by 2 mM
      ACPD was completely abolished by addition of 10 microM of the NMDA receptor
      antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10
      imine (MK-801), while 20 microM of the 2-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA)/kainic acid receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4
      tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) had no effect. Co-exposing
      cultures to a subtoxic dose of 300 microM ACPD together with 10 microM NMDA,
      which at this dose is known to induce a fairly selective degeneration of CA1
      pyramidal cells, significantly increased the PI uptake in both CA1 and CA3,
      compared to cultures exposed to 10 microM NMDA only. Adding the 300 microM ACPD
      as pretreatment for 30 min followed by a 30 min wash in normal medium before the
      ACPD/NMDA co-exposure, eliminated the potentiation of NMDA toxicity. The
      potentiation was also blocked by addition of 10 or 100 microM 2-methyl-6
      (phenylethynyl)pyridine (MPEP) (mGluR5 antagonist) during the co-exposure, while
      a corresponding addition of 10 or 100 microM 7-(hydroxyimino)cyclopropa[b]chromen
      1a-carboxylate ethyl ester (CPCCOEt) (mGluR1 antagonist) had no effect. We
      conclude that, stimulation of metabotropic glutamate receptors with ACPD at
      concentrations of 2 mM or higher induces a distinct subfield-related and time and
      concentration dependent pattern of hippocampal degeneration, and that ACPD at
      subtoxic concentrations modulates NMDA-induced excitotoxicity through the mGluR5
      receptor in a time dependent way.

PMID- 11292453
TI  - Sleep deprivation but not a whisker trim increases nerve growth factor within
      barrel cortical neurons.
AB  - Sleep is hypothesized to influence activity-driven changes in the brain
      microcircuitry. A change in the barrel cortex following the removal of the
      mystacial whiskers in rats is a model for synaptic plasticity. This model was
      combined with sleep deprivation and immunoreactivity for nerve growth factor
      (NGF) was determined. Sleep deprivation for 6 h after light onset significantly
      increased the number of NGF-immunoreactive pyramidal neurons in layer V of the
      barrel cortex. However, unilateral trimming of mystacial whiskers did not affect
      NGF immunoreactivity in the contralateral or ipsilateral barrel cortices when
      rats were allowed to sleep. If the rats received a unilateral whisker cut at
      light onset, and subsequently were deprived of sleep, increases in the NGF
      immunoreactive neurons were only observed in the barrel cortex on the side that
      received input from the remaining intact whiskers. In contrast, NGF
      immunoreactivity on the side contralateral to the cut whiskers decreased in sleep
      deprived animals to levels below those observed in the control animals that were
      allowed to sleep. These results suggest that NGF expression is influenced by the
      interaction of sleep, afferent input and the nature of ongoing synaptic
      reorganization. Further, results are consistent with the hypothesis that growth
      factors, such as NGF, form part of the mechanism responsible for sleep regulation
      and that they also form one facet of sleep-related synaptic plasticity.

PMID- 11292454
TI  - The anti-amnesic effects of sigma1 (sigma1) receptor agonists confirmed by in
      vivo antisense strategy in the mouse.
AB  - The sigma1 (sigma1) receptor cDNA was recently cloned in several animal species,
      including the mouse. In order to firmly establish the implication of sigma1
      receptors in memory, a phosphorothioate-modified antisense oligodeoxynucleotide
      (aODN) targeting the sigma1 receptor mRNA and a mismatched analog (mODN) were
      administered intracerebroventricularly for 3 days in mice. Scatchard analyses of
      in vitro (+)-[3H]SKF-10,047 binding to sigma1 sites showed that Bmax values were
      significantly decreased in the hippocampus (-58.5%) and cortex (-38.1%), but not
      in the cerebellum, of aODN treated mice, as compared to saline- or mODN-treated
      animals. In vivo binding levels were also significantly decreased after aODN
      treatment in the hippocampus and cortex but not in the cerebellum. The anti
      amnesic effects of the selective sigma1 agonists PRE-084 or SA4503 were evaluated
      against the learning impairments induced by dizocilpine or scopolamine,
      respectively, using spontaneous alternation behavior and passive avoidance task.
      The anti-amnesic effects of PRE-084 or SA4503, observed after saline- or mODN
      treatment, were blocked after aODN administration. These observations bring a
      molecular basis to the modulatory role of sigma1 receptors in memory processes.

PMID- 11292455
TI  - Adenosine permeation of a dynamic in vitro blood-brain barrier inhibited by
      dipyridamole.
AB  - Adenosine is an inhibitory neuromodulator in the central nervous system and has
      been reported to have neuroprotective properties. Using a dynamic in vitro blood
      brain barrier, we investigated the hypothesis that inhibition of adenosine
      transporters on the lumenal side of the blood-brain barrier may decrease the loss
      of adenosine from the brain. Our results indicate that lumenal administration of
      dipyridamole, a nucleoside transport inhibitor, can inhibit adenosine permeation
      from the extracapillary space into the lumen.

PMID- 11292456
TI  - Chronic ischemia preferentially causes white matter injury in the neonatal rat
      brain.
AB  - Chronic ischemic brain injuries were studied in 7- and 14-day-old rat pups, which
      were subjected to bilateral carotid artery occlusion (BCAO) on postnatal day 1.
      BCAO preferentially injured white matter in the corpus callosum, subcortex and
      internal capsule areas while largely spared cortical neurons. White matter
      rarefaction in the corpus callosum was observed in 12 out of the 17 BCAO rat
      brains and significantly enlarged lateral ventricles were found in five out of
      seven P14 BCAO rat brains. These white matter changes were similar to injuries
      found in newborn infants with periventricular leukomalacia (PVL). White matter
      injuries in the 7-day-old BCAO rat brain were accompanied with increased
      activation of microglia/macrophages, as indicated by ED1 and OX42 positive
      immunostaining. Immature oligodendrocytes in the 7-day-old BCAO rat brain, as
      indicated by O4+/O1+ staining, were much fewer than in the sham-operated rat
      brain. Immunostaining for myelin basic protein (MBP) at the fimbria hippocampus
      and the internal capsule areas in the 7-day-old BACO rat brain was also much less
      than in the control rat brain. Consistent with the immunostaining data, MBP mRNA
      expression in the 7-day-old, but not in the 14-day-old, BCAO rat brain was
      significantly less than in the control rat brain. The overall results suggest
      that pre-oligodendrocytes and immature oligodendrocytes might be major targets
      for chronic ischemic insults and activated microglia/macrophages are possibly
      involved in the process of white matter injury.

PMID- 11292457
TI  - Visual agnosia and Kluver-Bucy syndrome in marmosets (Callithrix jacchus)
      following ablation of inferotemporal cortex, with additional mnemonic effects of
      immunotoxic lesions of cholinergic projections to medial temporal areas.
AB  - Inferotemporal ablations in the New World monkey, the common marmoset (Callithrix
      jacchus), produced a persistent impairment on visual discrimination learning and
      a florid, but transient, Kluver-Bucy syndrome. Monkeys with these ablations were
      impaired on acquisition of object discriminations to a high criterion and on
      concurrent discrimination learning, to a single high criterion across all trials.
      Neither the control monkeys nor the monkeys with inferotemporal ablations found
      acquisition more difficult when the component discriminations of a set were
      presented concurrently compared to consecutively, although the monkeys with
      inferotemporal ablations found acquisition under both these conditions somewhat
      more difficult than did control monkeys. This suggests that the severe impairment
      caused by inferotemporal ablations on concurrent learning measured across all
      trials is due to the need for sustained performance across a concurrent set
      rather than to the extra mnemonic demands of concurrent presentation. When
      immunotoxic lesions of the cholinergic projection to the hippocampal formation
      were added to the inferotemporal ablations, a further impairment on retention,
      and a differential impairment on concurrent, compared to consecutive, learning
      was observed. Previous studies have shown that lesions of the cholinergic
      projection to the hippocampus alone, or excitotoxic hippocampal lesions, do not
      affect simple visual discrimination learning. It is suggested that large
      inferotemporal ablations in monkeys produce a visual agnosia which causes severe
      'psychic blindness' in the first instance, and a persistent impairment on visual
      discrimination learning. The hippocampus makes a contribution, which may be
      mnemonic, to discrimination performance after inferotemporal ablations.

PMID- 11292458
TI  - Down-regulation of cell surface insulin receptors by sarco(endo)plasmic reticulum
      Ca2+-ATPase inhibitor in adrenal chromaffin cells.
AB  - Long-term (> or =12 h) treatment of cultured bovine adrenal chromaffin cells with
      thapsigargin (TG), an inhibitor of sarco(endo)plasmic reticulum Ca2+-ATPase
      (SERCA), caused a time (t(1/2)=16.3 h)- and concentration (IC50=37.8 nM)
      dependent decrease of cell surface 125I-insulin binding by 35%, but did not
      change the Kd value. TG caused a sustained increase of cytoplasmic concentration
      of Ca2+ ([Ca2+]c) in a biphasic manner, and the effect of TG on 125I-insulin
      binding was abolished by BAPTA-AM. Western blot analysis showed that TG lowered
      insulin receptor (IR) beta-subunit level in membrane, but did not alter total
      cellular levels of IR precursor and IR beta-subunit. Internalization of cell
      surface IR, as measured by using brefeldin A, an inhibitor of vesicular exit from
      the trans-Golgi network (TGN), was not changed by TG. These results suggest that
      inhibition of SERCA by TG and the subsequent increase of [Ca2+]c down-regulates
      cell surface IR by retarding externalization of IR from the TGN.

PMID- 11292459
TI  - Differential localization of acetylcholinesterase in relation to pre- and
      postsynaptic nicotinic receptors in the chick brain.
AB  - Immunofluorescence and confocal microscopy were combined to study the
      distribution of acetylcholinesterase in relation to the localization of the beta2
      subunit of the nicotinic acetylcholine receptors in the chick brain. In several
      areas where the beta2 subunit is recognizably part of presynaptic receptors, the
      localization of acetylcholinesterase appeared not to overlap the localization of
      beta2. On the other hand, acetylcholinesterase and the beta2 subunit exhibited a
      strictly matching localization in areas where postsynaptic nicotinic receptors
      are known to be present. These data may represent a morphological substrate for
      possible differential actions of acetylcholinesterase at presynaptic and
      postsynaptic nicotinic sites.

PMID- 11292460
TI  - Localization of kappa opioid receptors in oxytocin magnocellular neurons in the
      paraventricular and supraoptic nuclei.
AB  - It has been demonstrated previously that kappa opioid receptor agonists, such as
      dynorphin, inhibit oxytocin secretion in the rat. To determine whether kappa
      agonists act directly on oxytocin-containing magnocellular neurons to inhibit
      hormone secretion, we utilized immunofluorescence to examine the cellular
      localization of kappa opioid receptors in the rat paraventricular and supraoptic
      nuclei. kappa Opioid receptor immunoreactivity co-localized with oxytocin
      containing cell bodies, their axons and axon terminals. Thus, our results suggest
      that kappa opioid receptor agonists can exert direct inhibitory actions on
      oxytocin magnocellular neurons.

PMID- 11292461
TI  - A significant participation of orexin-A, a potent orexigenic peptide, in the
      preovulatory luteinizing hormone and prolactin surges in the rat.
AB  - Orexins are novel hypothalamic peptides which stimulate food intake. In view of
      the well-known tight connection between the nutritional state and the
      reproductive function, in this study we examined a possible role of orexin-A in
      the generation of ovarian steroid-induced luteinizing hormone (LH) and prolactin
      (PRL) surges in ovariectomized rats. Experiments were performed on both normally
      fed and 3-day-fasted rats. Although fasting led to abolition of both LH and PRL
      surges, intracerebroventricular administration of orexin-A (0.3 and 3.0 nmol)
      resulted in a dose-dependent recovery of the hormonal surges. In addition, anti
      orexin-A antisera given to normally-fed rats completely abrogated the surges of
      both hormones. These results demonstrate for the first time a significant
      participation of orexin-A in the preovulatory LH and PRL surges in the rat.

PMID- 11292463
TI  - Behavioral sensitization to WIN55212.2 in rats pretreated with heroin.
AB  - There is evidence of similarities and interactions between central opioid and
      cannabinoid system with reference to drug reinforcement and abuse. Here we
      demonstrate that repeated injection of heroin produces behavioral sensitization
      towards administration of the synthetic cannabinoid receptor agonist WIN55212.2
      in the rat. These effects were blocked by both the cannabinoid antagonist
      SR141716A and the opioid antagonist naloxone. These findings suggest that
      repeated exposure to heroin produces neuroadaptative changes in brain circuits
      that contribute to mediate the behavioral consequences of acute administration of
      WIN55212.2. The present results expand our knowledge on the interactions between
      central opioid and cannabinoid systems with respect to drug abuse.

PMID- 11292462
TI  - Monoclonal antibodies to alphaI spectrin Src homology 3 domain associate with
      macropinocytic vesicles in nonerythroid cells.
AB  - Spectrins represent a family of membrane-associated proteins responsible for
      membrane flexibility and cell shape in erythrocytes, and probably in most
      nonerythroid cells. Spectrin functions as a tetramer consisting of two
      heterodimers each containing two subunits termed alpha and beta. In humans,
      alphaI and alphaII spectrins but not beta spectrins are characterized by the
      presence of an Src homology 3 (SH3) domain. As a tool to investigate the function
      of spectrin SH3 domains we derived several monoclonal antibodies (mAb) to the
      recombinant human alphaI or alphaII spectrin SH3 domain. Immunostaining using
      these monoclonal antibodies indicated expression of alphaI spectrin in cell
      bodies and alphaII spectrin in neurites of granule neurons in mouse primary
      cerebellar cultures. Monoclonal antibodies reactive to alphaI spectrin SH3 domain
      indicated expression of a protein(s) containing an alphaI-like SH3 domain in
      cytoplasmic vesicular-like structures in GFAP-positive cells in these cultures.
      In NIH 3T3 fibroblasts, these antibodies label macropinocytic vesicles. Together,
      these data and Western blotting results suggest expression of at least three
      spectrin-SH3 domain antibody-reactive proteins.

PMID- 11292464
TI  - Alpha-synuclein protein is not scavenged in neuronal loss induced by kainic acid
      or focal ischemia.
AB  - Alpha-synuclein, a presynaptic protein, is markedly included in Lewy bodies (LB)
      in Parkinson's and LB diseases. In this study, neuronal loss and the activation
      of glial cells such as microglia and astrocytes were induced by neurodegenerative
      insults such as the injection of kainic acid and occlusion of the middle cerebral
      artery. In contrast, immunoreactivity for alpha-synuclein did not change even at
      7 days after these insults. These results suggest that alpha-synuclein protein
      may be so scarcely scavenged by glial cells that it readily condenses in
      neurodegenerative regions.

PMID- 11292465
TI  - Estrogen increases G protein coupled receptor kinase 2 in the cortex of female
      rats.
AB  - Treatment of ovariectomized female rats with estrogen for 2 days reduces alpha2
      adrenoceptor binding density by 25%, increases G protein coupled receptor kinase
      (GRK) activity by 50% and elevates GRK 2 protein levels by 50% in the frontal
      cortex. These results suggest that estrogen may decrease alpha2-adrenoceptor
      expression in the frontal cortex of female rats by regulating GRK 2.

PMID- 11292466
TI  - Developmental changes in progesterone biosynthesis and metabolism in the quail
      brain.
AB  - We have recently demonstrated that the quail brain possesses the cholesterol side
      chain cleavage enzyme (cytochrome P450scc) and 3beta-hydroxysteroid
      dehydrogenase/Delta5-Delta4-isomerase (3beta-HSD) and produces pregnenolone,
      pregnenolone sulfate and progesterone from cholesterol. To elucidate the
      developmental changes in progesterone biosynthesis and its metabolism in the
      quail brain, we examined the expression and activity of 3beta-HSD and
      progesterone metabolite(s) during embryonic and post-hatched ages. Both the
      progesterone concentration and 3beta-HSD mRNA expression in the brain were almost
      constant during embryonic and post-hatched ages. The conversion of pregnenolone
      to progesterone (net 3beta-HSD enzymatic activity) was also constant during
      development and at maturity. However, without radioinert progesterone, the
      production of progesterone was drastically reduced in the embryonic brain,
      indicating active progesterone metabolism at the embryonic stage. Biochemical
      analysis together with HPLC and TLC revealed that only the embryonic brain
      actively produced 5beta-dihydroprogesterone from progesterone. Thus, progesterone
      production may be constant during embryonic and post-hatched development and in
      adulthood, whereas 5beta-dihydroprogesterone may be produced actively only in
      embryonic life due to 5beta-reductase.

PMID- 11292468
TI  - Oral contraception and ear disease: findings in a large cohort study.
AB  - A number of authors have suggested that oral contraceptives may increase the risk
      of certain ear diseases, especially otosclerosis and vestibular disorders,
      although the amount of published information on this topic is limited. We have
      analyzed the available data on ear disease in the Oxford-Family Planning
      Association contraceptive study that includes 17,032 women followed for periods
      of up to 26 years. No evidence of any adverse effect of oral contraceptives on
      ear disease was detected. A protective effect of oral contraceptives against wax
      in the ear has been described in the Royal College of General Practitioners oral
      contraception study. The amount of data available in the Oxford-Family Planning
      Association study was too small to permit confirmation or refutation of this
      finding.

PMID- 11292467
TI  - Cervical neoplasia risk in women provided hormonal contraception without a Pap
      smear.
AB  - The study was conducted to determine whether women using a demonstration program
      providing hormonal birth control without concurrent pelvic examination (First
      Stop) are at higher risk of cervical neoplasia compared to women using
      traditional family planning clinics. Using retrospective ion of medical charts,
      we compared risk factors for cervical neoplasia among 400 First Stop clients and
      400 traditional site clients matched on age, race, and contraceptive method. We
      determined prevalence of these factors: previous abnormal cervical smear, <16
      years at first intercourse, multiple sexual partners, high parity, history of
      sexually transmitted infections, and current cigarette smoking. First Stop
      clients were not at greater likelihood of having any risk factor for cervical
      neoplasia except high parity. First Stop clients who failed to follow through on
      a referral to a traditional clinic were not more likely to be of higher risk than
      those who did follow through. Of 13 First Stop clients with the highest risk
      profiles (previous abnormal cervical smear plus one other risk factor), one did
      not follow through with referral. First Stop clients choosing hormonal
      contraception without a pelvic examination do not appear to be at substantially
      higher risk of cervical neoplasia. Future research should quantify more precisely
      the risks and benefits of the general application of this strategy on a
      population level.

PMID- 11292469
TI  - The relationship between use of oral contraceptives and myocardial infarction in
      young women with fatal outcome, compared to those who survive: results from the
      MICA case-control study.
AB  - To examine the relationship between use of oral contraceptives and the risk of
      dying from myocardial infarction, we made a comparison of deceased patients and
      live patients (women aged less than 45) identified for the Myocardial Infarction
      Causality case-control study, using data obtained from general practice medical
      notes. There were 422 live patients and 110 deceased patients of women with a
      myocardial infarction with data available. The adjusted odds ratio for exposure
      to second generation oral contraceptives and risk of death within 28 days of a
      myocardial infarction compared with no oral contraceptive use was raised (2.88,
      95% confidence interval 1.22-6.77), and this effect was not seen for other types
      of oral contraceptives including third generation oral contraceptive
      formulations. In absolute terms, between 47,000 and 71,000 women would have to be
      exposed to a second generation pill for one year to result in one extra death
      from myocardial infarction, and this risk applies mainly to smokers. The results
      suggest a slightly increased relative risk of death among those having a
      myocardial infarction associated with exposure to second generation oral
      contraceptives, but this represents a small absolute risk. Further work is
      required before any change in contraceptive practice should be advocated.

PMID- 11292471
TI  - Measuring the contraceptive efficacy of Persona.

PMID- 11292470
TI  - Minimal androgenic activity of a new oral contraceptive containing norethindrone
      acetate and graduated doses of ethinyl estradiol.
AB  - The pharmacokinetics and androgenic activity of Estrostep, a new oral
      contraceptive providing low-dose estrogen in a graduated sequence with a constant
      dose of progestin, were characterized in an open-label, nonrandomized study in 17
      normally cycling women treated for three cycles with Estrostep. Women received 1
      mg of norethindrone acetate daily combined with 20 microg of ethinyl estradiol
      daily for the first 5 days (1/20), 30 microg of ethinyl estradiol daily for the
      next 7 days (1/30), and 35 microg of ethinyl estradiol daily for 9 days (1/35).
      No medication was given for 7 days in each cycle to allow for withdrawal
      bleeding. Serial blood samples for the measurement of ethinyl estradiol and
      norethindrone concentrations were collected on days 5, 12, and 21 of the third
      treatment cycle for the 1/20, 1/30, and 1/35 dose, respectively. Sex hormone
      binding globulin (SHBG) and free testosterone were measured at baseline, on day 1
      of cycles 2 and 3 (SHBG only), and on days 5, 12, and 21 of cycle 3. Mean steady
      state plasma ethinyl estradiol and norethindrone concentrations increased over
      cycle 3. The increases in ethinyl estradiol concentrations were proportional to
      dose. The increases in norethindrone concentrations were related to ethinyl
      estradiol-dependent increases in SHBG concentrations, which were 218%, 253%, and
      296% of baseline values on days 5, 12, and 21, respectively. Mean plasma free
      testosterone concentrations decreased 47%, 60%, and 64% below baseline on days 5,
      12, and 21 of cycle 3, respectively. Graduated ethinyl estradiol doses combined
      with a constant norethindrone acetate dose progressively increase SHBG and
      decrease free testosterone, which overrides any theoretic concerns of androgenic
      activity of norethindrone acetate. Although true androgenic activity can be
      determined only by assessing endpoints such as acne, hirsutism, and lipids in
      large controlled trials, the observed changes in circulating SHBG and free
      testosterone concentrations indicate that Estrostep has little, if any, intrinsic
      androgenic activity.

PMID- 11292472
TI  - Evaluation of a media campaign to increase knowledge about emergency
      contraception.
AB  - Our objective was to evaluate a media campaign designed to increase knowledge
      about emergency contraception. Random telephone surveys were conducted before and
      after the campaign to measure changes in knowledge about emergency contraception.
      Change in the volume of calls to the Emergency Contraception Hotline (1-888-NOT-2
      LATE) was a secondary measure of impact. Significant increases occurred in the
      proportions of women who knew that something could be done after intercourse to
      prevent pregnancy, who knew the term emergency contraception, who knew of the 72
      h time limit, and who had heard of the Hotline. In addition, the number of calls
      to the Hotline increased substantially. A public education media campaign
      resulted in significant increases in knowledge about emergency contraception. The
      first contraception advertisement ever shown on television did not provoke
      controversy.

PMID- 11292473
TI  - Outpatient second trimester pregnancy termination.
AB  - We evaluated the efficacy of initiating a second trimester medical abortion
      outside of a health care facility using patient self-administered serial
      intravaginal misoprostol. Patients scheduled for second trimester medical
      termination of pregnancy were randomized to an inpatient or outpatient group.
      Both groups received a single 200-microg vaginal misoprostol tablet every 6 h. No
      other abortifacients were used. The home group self-administered the misoprostol
      and returned to the hospital for clinical reasons or after 24 h and again at 48
      h. Forty-two women were assigned to the inpatient and 45 to the outpatient
      groups. There was no difference between the groups in demographics or indications
      for terminations. The median hours from first misoprostol to delivery of the
      fetus was 12 and 14 (inpatient versus outpatient, respectively; p = 0.28). The
      total median hours in hospital were 24 versus 11 (inpatient versus outpatient,
      respectively; p <0.05). Two patients (4%) in the outpatient group delivered the
      fetus outside of the hospital. There were no cases of hemorrhage in either group.
      Outpatient initiation of second trimester medical termination with self
      administered misoprostol is effective and decreases time of hospitalization.

PMID- 11292474
TI  - Effect of vaginally administered fumagillin on the morphology of implantation
      stage endometrium in the rhesus monkey.
AB  - Intravaginal administration of an anti-angiogenic agent, fumagillin, during
      blastocyst implantation, inhibits pregnancy establishment in a dose-related
      manner in the rhesus monkey. In the present study, mated female rhesus monkeys
      were vaginally inserted with tampons containing vehicle (group 1; n = 5) and test
      agent (fumagillin, 4 mg/animal; group 2; n = 6) on cycle day 20, and endometrial
      tissue samples were collected on cycle day 24 from all monkeys and processed for
      morphometric and ultrastructural analysis. Concentrations of estradiol-17beta,
      progesterone and chorionic gonadotrophin in peripheral circulation were
      determined. From serum profiles of hormones, two monkeys in group 1, and one
      animal in group 2 appeared pregnant. Endometrial morphology revealed histologic
      evidence of pregnancy in three of six fumagillin-treated animals, while other
      three fumagillin-treated animals showed degenerative changes in glands and
      venules along with marked extravasation. It is possible that the function of
      corpus luteum was affected by fumagillin treatment resulting in inadequate
      progesterone production (p <0.05), and consequent inadequate endometrial
      secretory preparation and receptivity, as revealed from decline in apical
      movement of vacuoles (p <0.05) and increase (p <0.05) in extravasation of red
      cells and leukocytes.

PMID- 11292475
TI  - Effects of tamoxifen metabolites on fertility of male rat.
AB  - The effects of chronic oral administration of tamoxifen citrate, at a dose of 0.4
      mg/kg/day, were compared to those of subcutaneous (s.c) administration of
      tamoxifen citrate, 4-hydroxy tamoxifen, N-desmethyl tamoxifen and intermittent
      oral tamoxifen administration on the fertility of the male rat and its post
      reversal progeny. The fertility parameters of 120 day-treated male rat sires from
      all groups and post reversal male F1 progeny of tamoxifen-treated sires were
      assessed. Chronic tamoxifen treatment via oral or s.c. routes reduced the
      fertility of the male rat, weights of accessory sex glands, serum luteinizing
      hormone, and testosterone levels without altering potency or sperm counts.
      However, antifertility effects of s.c. treatment were comparatively more
      consistent than those of oral treatment. 4-hydroxy and N-desmethyl tamoxifen
      failed to produce significant antifertility effects in the male rat. The
      antifertility effects of intermittent oral treatment were more sustained than
      those of chronic oral tamoxifen treatment. It is inferred that hepatic metabolism
      of tamoxifen interferes with its antifertility effects via oral route and that
      the parameters affected by chronic oral exposure in the male sires are completely
      reversed in progeny ensuing after an adequate period of drug withdrawal.

PMID- 11292476
TI  - Validity of an ELISA for N-acetyltransferase-2 (NAT2) phenotyping.
AB  - A competitive antigen ELISA was previously developed for NAT2 phenotyping, using
      caffeine as the probe drug. The ELISA phenotypes by measuring the ratio of 5
      acetamido-6-amino-3-methyluracil (AAMU) and 1-methylxanthine (1X) after
      transformation of 5-acetamido-6-formylamino-3-methyluracil (AFMU) to AAMU, in
      contrast to capillary electrophoresis high-pressure liquid chromatography (HPLC)
      which phenotype by measuring the AFMU/1X ratio. The ELISA phenotyping was
      previously determined in 30 samples and correlated well with phenotypes
      determined by capillary electrophoresis (29/30). The correlation was extended
      with the standard HPLC methodology by expanding the data set by 146 in order to
      test the validity of the ELISA methodology. The correlation with HPLC in this
      larger sample size was 96%; whereas the correlation between the two methods for
      determination of 1X was high (r(2)=0.90), that for determination of AAMU by ELISA
      and AFMU by HPLC was low (r(2)=0.53). The poor correlation between the two
      methodologies could not be attributed to the age of urine samples, nor to a
      significant decomposition of AFMU in the body prior to collection of the urine
      sample. The addition of a simple caffeine metabolite extraction method,
      originally developed for HPLC analysis of metabolites, to the ELISA phenotyping
      protocol produced a methodology with absolute correlation to the standard HPLC
      method.

PMID- 11292477
TI  - An evaluation of the colorimetric assays based on enzymatic reactions used in the
      measurement of human natural cytotoxicity.
AB  - In recent years colorimetric assays based on an enzymatic reaction such as the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay have been
      used in an attempt to replace the conventional isotopic assay for cell-mediated
      cytotoxicity. To clarify the problems in the colorimetric assays for natural
      cytotoxicity, K562 cells were employed as target cells and peripheral mononuclear
      cells (PBMCs) from cancer patients were used as effector cells. No correlation
      was found between the 51Cr assay and the MTT assay (P>0.05) or the N-acetyl-beta
      D-glycosaminidase (NAG) release assay (P>0.05) in 16 cancer patients. Labeling
      effector cells showed that the 51Cr release levels of such cells in 19
      chemotherapy patients were significantly higher than the levels from target cells
      in this group (P<0.01) and from effector cells in the control group (P<0.01).
      There was no correlation between the positive and negative 51Cr assays (P>0.05).
      The sensitivity of the MTT assay was greatly decreased by washing K562 cells
      prior to loading MTT solution. Enzyme release occurs as a result of cell
      metabolism and elevated enzyme release is associated with freezing. These
      findings indicate that the colorimetric assays based on an enzymatic reaction are
      not suitable for the detection of natural cytotoxicity in all populations, and
      are especially not suitable for the assay of natural cytotoxicity in chemotherapy
      patients.

PMID- 11292478
TI  - An ELISA for five glycolipids from the cell wall of Mycobacterium tuberculosis:
      Tween 20 interference in the assay.
AB  - Mycobacterium tuberculosis cell wall contains antigenic glycolipids: phenol
      glycolipid (PGL), diacyltrehalose (DAT), triacyltrehalose (TAT), cord-factor
      (CF), and sulpholipid-I (SL-I). In the last decade, the usefulness of these
      antigens for the serodiagnosis of tuberculosis has been evaluated mainly using
      enzyme-linked immunosorbent assays (ELISA). Currently, there are no conclusive
      results about the utility of these glycolipidic antigens, because the results
      obtained by different groups are discrepant. In order to explain these
      discrepancies, we have investigated the methodological variations in the ELISAs
      used previously. Specifically, we have studied the following: the coating
      solvent, the optimum amount of glycolipid coated per well, the blocking agent,
      and the use of detergent (Tween 20) in the washing buffer. The most significant
      finding was that Tween 20 detaches PGL, DAT, TAT and SL-I from microtitre wells.
      However, Tween 20 does not remove CF from the wells. In addition, we have found
      that the best solvent for coating is n-hexane, that the optimum antigen coating
      concentration is 1000 ng/well, and that BSA and gelatin are equally effective
      blocking agents. We can therefore conclude that the use of Tween 20 as a
      detergent, and the lower antigen coating concentrations (100-200 ng/well), may
      well explain some of the discrepancies in previous studies.

PMID- 11292479
TI  - Targeting antigen-specific receptors on B lymphocytes to generate high yields of
      specific monoclonal antibodies directed against biologically active lower
      antigenic peptides within presenilin 1.
AB  - We describe a targeting technique that selects antigen-specific receptors on B
      lymphocytes using antigen driven selective production of monoclonal antibodies
      which are directed against functional peptide sequences within the presenilin 1
      molecule that is believed to be related to the early-onset of familial
      Alzheimer's disease. Three different peptide sequences of presenilin 1 were
      constructed, one including the region around the amino acid position 300, where
      the putative cleavage site exists and the other two present in the N- and C
      terminal regions of that site. The efficiency in production of the desired
      monoclonal antibodies was at least 5-40-fold that obtained with the poly(ethylene
      glycol) (PEG)-mediated method. In addition, monoclonal antibodies directed
      against each of the peptide sequence displayed a high specificity for the
      corresponding peptide, in contrast to the lack of success using the PEG method.
      Also, the selection of surface immunoglobulin receptors on B lymphocytes by the
      peptides of interest was confirmed by immunofluorescent analysis. Here we
      demonstrate that targeting B lymphocytes results in the successful and efficient
      production of highly specific monoclonal antibodies against the lower antigenic
      peptide sequences.

PMID- 11292480
TI  - A C3 convertase assay for nephritic factor functional activity.
AB  - C3 nephritic factor (C3NeF) is an autoantibody against the C3 convertase which
      stabilizes this otherwise inherently labile neoenzyme and induces a continuous
      activation of the alternative pathway with C3 depletion. NeF is found in patients
      with membranoproliferative glomerulonephritis and/or partial lipodystrpohy. NeF
      activity is usually detected in plasma by hemolytic tests. In order to obtain
      reproducible data for the functional activity of purified C3NeF IgG a solid phase
      assay was developed. C3 convertase was generated on immobilized C3b by incubation
      with factors B and D in the presence of Ni(2+). Convertase sites were left to
      decay in the presence of normal IgG or NeF IgG. Residual convertase activity was
      measured by adding 125I-C3 and capturing nascent 125I-C3b on the plate surface
      via covalently coupled NH2-Glu-Tyr dipeptide. In the presence of factor H during
      C3 convertase decay, a dose dependent stabilizing activity was shown for NeF IgG
      including NeF IgG purified from urine. A second format of the assay was developed
      in which C3 convertase was assembled on C3b(2)-IgG complexes in the presence of
      Mg(2+). Since these complexes are more efficient as convertase precursors the
      signal was five-fold higher than with C3b. Convertase decay, on the other hand,
      was not influenced by the nature of the precursor and in both systems the
      stabilizing activity of NeF IgG was similar.

PMID- 11292481
TI  - A method to detect particle-specific antibodies against Ku and the DNA-dependent
      protein kinase catalytic subunit in autoimmune sera.
AB  - Sera from patients with systemic lupus erythematosus, polymyositis, scleroderma,
      and mixed connective tissue disease are frequently characterized by the presence
      of high levels of autoantibodies directed against linked sets of nuclear
      proteins. One of these autoantigen systems is made up of Ku and the DNA-dependent
      protein kinase catalytic subunit (DNA-PKcs), proteins that are essential for
      double-strand DNA break repair and for the related process of V(D)J
      recombination. Ku and DNA-PKcs bind avidly to DNA ends in vivo and in vitro and
      form an active protein kinase complex. One hypothesis is that this assembled
      nucleoprotein particle, rather than its component proteins, is a primary trigger
      for the autoimmune response and thus a major target for the resulting
      autoantibodies. To screen for particle-specific antibodies, we developed an assay
      in which the fully native nucleoprotein particle is reconstituted in vitro and is
      tethered to the surface of an ELISA plate via a streptavidin-biotin linkage.
      These particles are recognized efficiently by monoclonal antibodies and by
      autoantibodies present in patient sera. The assay may detect a broader spectrum
      of epitopes than a conventional ELISA in which Ku and DNA-PKcs are adsorbed
      directly to a plastic surface. The method will be advantageous for high
      throughput screening for antibodies and other ligands that bind the assembled DNA
      dependent protein kinase complex.

PMID- 11292482
TI  - Improving the in vitro antigen specific T cell proliferation assay: the use of
      interferon-alpha to elicit antigen specific stimulation and decrease bystander
      proliferation.
AB  - The measurement of the proliferative response of primed T cells to an antigenic
      stimulus (lymphocyte transformation assay: LTT) is commonly used for determining
      T cell immune responsiveness. However, the ratio between the spontaneous and the
      antigen-triggered response (stimulation index) is frequently quite low (<3-5)
      making the interpretation difficult. We modified the assay by the addition of
      interferon-alpha and the use of fresh autologous serum instead of human AB pool
      serum. These measures significantly enhanced the stimulation index following
      stimulation with tetanus toxoid, Candida albicans and tick-borne encephalitis
      (TBE) viral antigen in studies of sensitized patients. There was no concomitant
      increase in false positive results. Kinetic studies showed a reduced nonspecific
      background proliferation of non-stimulated cultures particularly between days 4
      and 6 of culture. Furthermore, the positive effect of interferon-alpha were
      confirmed in studies of patients with contact allergy to nickel and gold. We
      conclude that this modified form of proliferation assay significantly increases
      the signal to noise ratio which can be attained. This may be of particular value
      when looking at T cell responses in immunocompromised patients or in diagnostic
      attempts to detect very low frequencies of antigen-specific T cells.

PMID- 11292483
TI  - Detection and localization of non-HLA-ABC antigenic sites relevant to kidney
      rejection on endothelial cells.
AB  - Immunological rejection of kidney allografts is usually attributed to
      presensitization to HLA antigens. However, data on HLA identical transplant
      rejections indicate that non-HLA antigens may also be involved, and it has been
      suggested that vascular endothelium represents the main target cell. The purpose
      of the present study is to describe a method of detecting non-HLA antibodies
      immunocytochemically. We showed the molecular independence between HLA-ABC
      molecules identified by the monoclonal antibody w6/32, and antigenic sites
      identified by a kidney rejection patient serum, previously characterized, on
      cultured endothelial cells isolated from human umbilical cords by collagenase
      digestion. Single immunofluorescence staining indicated the molecular
      independence between these antigenic sites, as the first serum showed a granular
      pattern, diffused throughout the cytoplasm and the other a reticular pattern
      restricted to the same cytoplasmic region. This result was confirmed by double
      labeling. Immunoelectronmicroscopy study also confirmed site independence,
      showing labeling patterns with different intensities and distinct localizations,
      using 10- and 20-nm colloidal gold particles to reveal HLA-ABC and non-HLA-ABC
      determinants, respectively. In conclusion, cultured endothelial cells may be used
      immunocytochemically to detect non-HLA-ABC determinants of antibody reactivity in
      renal graft recipients, and the indirect immunofluorescence may be the
      methodology of choice, since it is easy, reliable and low cost.

PMID- 11292484
TI  - Chemically de-acetylated 2',7'-dichlorodihydrofluorescein diacetate as a probe of
      respiratory burst activity in mononuclear phagocytes.
AB  - 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) is a fluorogenic probe
      commonly used to detect cellular production of reactive oxygen species (ROS), for
      example in the respiratory burst of granulocytes and mononuclear phagocytes. This
      method depends on the de-acetylation of H2DCFDA by cellular esterases, to form
      the oxidant-sensitive compound, 2',7'-dichlorodihydrofluorescein (H2DCF).
      Importantly, however, not all cells possess sufficient esterase activity to
      produce the H2DCF needed for accurate measurement of ROS. In this study, we used
      chemically de-acetylated probe (H2DCF) to assess the phorbol-ester-triggered
      respiratory burst of rainbow trout macrophages, which, like some mammalian
      mononuclear phagocytes, appear to have low probe-esterase activity. We compared
      this approach to the use of intact H2DCFDA and the cytochrome c reduction assay.
      The H2DCF and cytochrome c reduction assays gave similar portrayals of the
      kinetics of the macrophage respiratory burst, while H2DCFDA did not. We therefore
      recommend the use of H2DCF over H2DCFDA for quantification of the production of
      reactive oxygen species. Additionally, we stress the need to test reaction
      buffers or culture media used with H2DCF(DA) for their ability to oxidize the
      probe directly or indirectly. As an example, we have observed that tyrosine
      combined with ubiquitous metal contaminants of physiological buffers can result
      in high levels of oxidation, which may be incorrectly interpreted as cellular
      activity.

PMID- 11292485
TI  - Antigen-presenting hybridoma cells expressing MHC antigens of the LEW rat.
AB  - Towards the eventual purpose of facilitating analyses of specificities and
      functions of LEW rat T lymphocytes involved in the induction and development of
      organ-specific autoimmune disorders, hybridoma cells expressing class I and class
      II MHC antigens of LEW rat have been developed. B cell hybridomas produced
      between a murine B cell tumor M12.4.5 and stimulated LEW B cells expressed high
      levels of LEW class II MHC antigen but the expression of LEW class I MHC antigens
      on these cells was rather low. The B hybridoma cells were capable of presenting
      soluble protein antigens to LEW CD4(+) T cells. Furthermore, The use of this
      hybridoma revealed antigen-specific cytolytic activity of rat CD4(+) T cells. T
      cell hybridomas produced between murine thymoma BW5147 and LEW T cells expressed
      class I MHC antigens of the LEW rat. The expression was confirmed by surface
      staining and specific cytolysis by rat allogeneic CTL.

PMID- 11292486
TI  - Flow cytometric determination of intracellular or secreted IFNgamma for the
      quantification of antigen reactive T cells.
AB  - The detection of antigen-induced IFNgamma secretion at the single cell level can
      be used to identify and enumerate antigen-reactive T cells from peripheral blood.
      This study was performed to analyze the suitability of T cell enumeration by flow
      cytometry in comparison with the ELISPOT assay. Peripheral blood mononuclear cell
      (PBMC) samples from six HLA-A2+ healthy subjects were analysed for the frequency
      of influenza-reactive CD8+ T cells by flow cytometry detecting either
      intracellular IFNgamma (IC-FC) or secreted IFNgamma (S-FC). All samples were also
      analysed by IFNgamma ELISPOT assay. The frequency of influenza peptide-reactive T
      cells determined by IC-FC was 0.01 to 0.34% of CD8+ T cells and by ELISPOT assay
      0.02 to 0.23% of CD8+ T cells (n=6 subjects) with a high inter-assay
      reproducibility and a close correlation between the assays (r=0.77, P<0.001).
      Little or no IFNgamma production was observed in unstimulated PBMC samples using
      either the IC-FC or the ELISPOT assay. In contrast, using S-FC large numbers of
      IFNgamma-secreting CD8+ T cells (0.37% to 5.55%, n=6 subjects) were detected in
      unstimulated PBMC. The frequency of influenza-reactive CD8+ T cells (0.57-5.19%,
      n=6 subjects) determined by S-FC did not correlate with the values from the IC-FC
      or ELISPOT assays. This comparative study shows the suitability of the
      determination of frequencies of antigen reactive T cells in PBMC by IC-FC. The
      advantage of IC-FC is the possibility to phenotype simultaneously antigen
      reactive T cells.

PMID- 11292487
TI  - Autoreactivity, backstimulation and reproducibility in a helper T lymphocyte
      precursor assay.
AB  - Helper T lymphocyte precursor (HTLp) frequencies determined by limiting dilution
      analysis (LDA) have a predictive value for alloreactivity in allogeneic bone
      marrow transplantation. Methodological problems in LDA include autoreactivity in
      the responder or stimulator cell populations and interleukin 2 (IL-2) production
      by the stimulator cells as a response to the responder cells (backstimulation).
      The extent and impact of these aspects for IL-2 production and HTLp frequency
      determination were studied by autologous and allogeneic mixed lymphocyte
      reactions with healthy volunteers and HTLp determinations from bone marrow
      transplantation donor/recipient pairs. We found that autoreactivity occurred in
      the unirradiated cells with a reproducible inter-individual variation. The
      immunogenicity of the stimulator cells was preserved after gamma irradiation with
      50 Gy and the risks of autoreactivity and backstimulation were limited. Higher
      doses of irradiation decreased the immunogenicity. Immune reactions to antigens
      present in the serum supplement of the culture medium were seen with foetal calf
      serum and to a lesser extent with pooled human sera. This could be avoided by the
      use of autologous serum. We were unable to ensure satisfactory culture conditions
      in serum-free medium. The reproducibility of the HTLp frequency determinations
      was tested for intra- and inter-assay variation. The coefficients of variation
      were estimated as 24% and 35%, respectively. This was acceptable considering the
      range of the HTLp frequencies (1:10(2) to 1:10(7)). The influence of the extent
      of autoreactivity of the bone marrow donors was investigated in 28 HLA-identical
      sibling transplantations. We found no correlation between the autoreactivity of
      the donors and the HTLp frequencies. The extent of autoreactivity of the donor
      did not correlate with the clinical outcome in terms of acute graft-versus-host
      disease, treatment-related mortality, risk of relapse and overall survival. In
      spite of methodological difficulties and interference from autoreactivity and
      backstimulation, reproducible quantification of clinically significant
      alloreactivity can be attained.

PMID- 11292488
TI  - Expression of single-chain Fv-Fc fusions in Pichia pastoris.
AB  - Phage display technology makes possible the direct isolation of monovalent single
      chain Fv antibody fragments. For many applications, however, it is useful to
      restore Fc mediated antibody functions such as avidity, effector functions and a
      prolonged serum half-life. We have constructed vectors for the convenient, rapid
      expression of a single-chain antibody Fv domain (scFv) fused to the Fc portion of
      human IgG1 in the methylotrophic yeast Pichia pastoris. The scFv-Fc fusion
      protein is secreted and recovered from the culture medium as a disulfide-linked,
      glycosylated homodimer. The increased size of the dimer (approximately 106 kDa
      vs. approximately 25 kDa for a scFv) results in a prolonged serum half-life in
      vivo, with t(1/2) of the beta phase of clearance increasing from 3.5 h for a
      typical scFv to 93 h for a scFv-Fc fusion in mice. The scFv-Fc fusion is capable
      of mediating antibody-dependent cellular cytotoxicity against tumor target cells
      using human peripheral blood mononuclear cells as effectors. Finally, the Fc
      domain is a convenient, robust affinity handle for purification and
      immunochemical applications, eliminating the need for proteolytically sensitive
      epitope and/or affinity tags on the scFv.

PMID- 11292489
TI  - Altering the fine specificity of an anti-Legionella single chain antibody by a
      single amino acid insertion.
AB  - Antibody engineering provides the potential to clone and manipulate antibody
      genes to produce fragments with altered specificity. We have produced an anti-
      Legionella single chain fragment with broader specificity towards Legionella
      serotypes than the parent monoclonal antibody. Using this relationship between
      the parent monoclonal and the recombinant antibody derived from it as a model, we
      attempted to identify those residues responsible for this change in fine
      specificity. Sequence analysis of this recombinant antibody revealed the deletion
      of a conserved residue, Asp101, in the CDR-H3 region. Using site-directed
      mutagenesis, we have created a mutant form of this single chain fragment with an
      aspartic acid insertion mutation at position 101 of the antibody heavy chain.
      This mutant scFv demonstrates improved specificity compared to the wild-type
      recombinant antibody, indicating an important role for Asp101.

PMID- 11292490
TI  - Development of a quantitative assay for residual host cell proteins in a
      recombinant subunit vaccine against human respiratory syncytial virus.
AB  - We have developed and validated a process-specific immunoligand assay based on
      the Threshold system for the quantification of residual host cell proteins (HCPs)
      in a recombinant subunit vaccine candidate against the human respiratory
      syncytial virus (hRSV). The industrial process of this vaccine produced in
      Escherichia coli, involved five chromatography steps for the production of
      clinical-grade batches. The clearance of non-product-related protein throughout
      the purification process was documented by the evaluation of the HCP content in
      the chromatographic fractions at each step of the downstream processing. The
      assay had a detection limit of 0.5 ng/ml of HCP equivalent to 10 parts per
      million (ppm). The quantification limit was 1.3 ng/ml of HCP, giving a
      sensitivity range of the assay of 10 to 30 ppm. To our knowledge, this is the
      first sensitive HCP assay reported for a vaccine.

PMID- 11292491
TI  - An improved procedure for the generation of recombinant single-chain Fv antibody
      fragments reacting with human CD13 on intact cells.
AB  - A procedure was developed to generate recombinant single chain Fv (scFv) antibody
      fragments reacting with the extracellular domain of human cell surface antigen
      CD13 (hCD13; aminopeptidase N) on intact cells. Membrane fractions prepared from
      a stably transfected hCD13-positive murine NIH/3T3 cell line were used to
      immunize BALB/c mice, with the intention that hCD13 would be the major
      immunogenic molecule recognized by the immune system. Spleen RNA from the
      immunized mice served to generate a combinatorial scFv phage display library. The
      library was adsorbed against non-transfected NIH/3T3 or Sf21 insect cells to
      eliminate nonrelevant binders. The supernatant was then used for panning with
      either hCD13-transfected Sf21 insect cells or a hCD13-expressing human leukemia
      derived cell line. Therefore, the key concepts of the procedure were the
      presentation of hCD13 as the sole human antigen on murine NIH/3T3 cells and a
      screening strategy where hCD13 was the major common antigen of the material used
      for immunization and panning. Two different hCD13-reactive phages were isolated
      and the soluble scFvs were expressed in E. coli and purified. The two scFvs, anti
      hCD13-1 and anti-hCD13-3, differed at four amino acid positions in their V(H)
      regions and both had high affinities for hCD13 as determined by surface plasmon
      resonance (K(D)=7 and 33x10(-10) M, respectively). Both efficiently recognized
      hCD13 on intact cells. Therefore, the procedure allowed the production of high
      affinity scFvs reacting with a desired antigen in its native conformation without
      requiring extensive purification of the antigen and should be useful for the
      preparation of scFvs against other conformation-sensitive cell-surface antigens.

PMID- 11292492
TI  - Identification of a peptide that protects the human acetylcholine receptor
      against antigenic modulation.
AB  - mAb 192 is a rat monoclonal antibody with very high affinity for the major
      immunogenic region (MIR) of the human muscle acetylcholine receptor (AChR). An
      epitope mimic of this antibody was selected from a phage display peptide library
      screened with mAb 192. The peptide-presenting phage has been shown to
      specifically bind to solid phase mAb 192 with an equilibrium dissociation
      constant (K(d)) of 8.45x10(-9) M, as directly measured with surface plasmon
      resonance. This value represents the avidity of the interaction between selected
      phage and mAb 192. A synthetic version of this peptide QPSPYNGWRMEI, referred to
      as MG15, binds to its selecting antibody and blocks the interaction of mAb 192
      with human AChR. Peptide MG15 was able to protect acetylcholine receptors on
      human RD cells from antibody-mediated down-modulation. The negative charge of
      glutamic acid plays a important role in antibody binding. Replacement of the
      glutamic acid with an alanine completely abolishes the inhibitory activity.

PMID- 11292493
TI  - Protein affinity maturation in vivo using E. coli mutator cells.
AB  - This protocol provides a simple in vivo strategy for introducing random mutations
      to a target DNA sequences using E. coli mutator cells. The method has been used
      in our laboratory for affinity maturation of proteins encoded by target DNA
      sequences. Selection conditions can be modified for antibody fragments with
      increased production levels. Growth conditions in E. coli mutator cells can be
      adjusted to introduce a single random point mutation per kilobase of DNA,
      approximately equivalent to one codon change per scFv fragment.

PMID- 11292494
TI  - A stochastic model for disease transmission in a managed herd, motivated by
      Neospora caninum amongst dairy cattle.
AB  - A stochastic model for the spread of Neospora caninum infection within a herd of
      dairy cattle is studied, in particular the long-term (equilibrium) behaviour of
      the model. The model incorporates the interesting feature that total herd size is
      constrained to lie within a fairly small interval, but not held exactly constant.
      Approximations for the joint distribution of numbers of susceptible and infected
      individuals present in equilibrium are derived based upon a diffusion
      approximation to the infection process. The effect of both 'typical herd size'
      and 'the amount of permitted variation in herd size' upon disease prevalence in
      equilibrium are considered using both the exact equilibrium distribution of the
      process and our approximations.

PMID- 11292495
TI  - Equivalence transformations for dendritic Y-junctions: a new definition of
      dendritic sub-unit.
AB  - A sequence of equivalence transformations is used to represent the mathematical
      model of a simply branched neuron with non-homogeneous membrane properties and
      non-uniform geometry by an entirely equivalent model of an unbranched structure.
      The analysis indicates how neuronal morphology, in combination with its
      biophysical properties, shapes neuronal output in response to current input. The
      equivalence transformations described here reveal the types of operations that
      are likely to feature in the analysis of complex multi-branched structures,
      neuronal or otherwise. These transformations provide a new definition of
      dendritic sub-unit and a basis of a mechanism for characterising local and non
      local signal processing within dendritic structures. It is anticipated that the
      capacity to transform biological neurons into an equivalent unbranched structure
      will make an important contribution to the understanding of the functional role
      of neuron geometry as well as to the construction of silicon neurons with
      realistic biological properties.

PMID- 11292496
TI  - From periodic travelling waves to travelling fronts in the spike-diffuse-spike
      model of dendritic waves.
AB  - In the vertebrate brain excitatory synaptic contacts typically occur on the tiny
      evaginations of neuron dendritic surface known as dendritic spines. There is
      clear evidence that spine heads are endowed with voltage-dependent excitable
      channels and that action potentials invade spines. Computational models are being
      increasingly used to gain insight into the functional significance of a spine
      with an excitable membrane. The spike-diffuse-spike (SDS) model is one such model
      that admits to a relatively straightforward mathematical analysis. In this paper
      we demonstrate that not only can the SDS model support solitary travelling
      pulses, already observed numerically in more detailed biophysical models, but
      that it has periodic travelling wave solutions. The exact mathematical treatment
      of periodic travelling waves in the SDS model is used, within a kinematic
      framework, to predict the existence of connections between two periodic spike
      trains of different interspike interval. The associated wave front in the
      sequence of interspike intervals travels with a constant velocity without
      degradation of shape, and might therefore be used for the robust encoding of
      information.

PMID- 11292497
TI  - Optimal harvesting and stability for a two-species competitive system with stage
      structure.
AB  - In this paper, we consider a stage-structured competitive population model with
      two life stages, immature and mature, with a mature population of harvesting. We
      obtain conditions for the existence of a globally asymptotically stable positive
      equilibrium and a threshold of harvesting for the mature population. The optimal
      harvesting of the mature population is also considered.

PMID- 11292498
TI  - A stochastic modeling of early HIV-1 population dynamics.
AB  - In a recent paper, Tuckwell and Le Corfec [J. Theor. Biol. 195 (1998) 450-463]
      applied the multi-dimensional diffusion process to model early human
      immunodeficiency virus type-1 (HIV-1) population dynamics. The purpose of this
      paper is to assess certain features and consequences of their model in the
      context of Tan and Wu's stochastic approach [Math. Biosci. 147 (1998) 173-205].

PMID- 11292499
TI  - Global stability of an SEIS epidemic model with recruitment and a varying total
      population size.
AB  - This paper considers an SEIS epidemic model that incorporates constant
      recruitment, disease-caused death and disease latency. The incidence term is of
      the bilinear mass-action form. It is shown that the global dynamics is completely
      determined by the basic reproduction number R(0). If R(0)<or=1, the disease-free
      equilibrium is globally stable and the disease dies out. If R(0)>1, a unique
      endemic equilibrium is globally stable in the interior of the feasible region and
      the disease persists at the endemic equilibrium.

PMID- 11292500
TI  - Change in feature space is not necessary for the flash-lag effect.
AB  - To achieve perceptual match between a flashed target and a gradually changing
      one, the flashed target should have the feature value corresponding to the value
      to be obtained by the gradually changing target only later. Flashed target should
      be positioned ahead of the continuously moving one in order to be perceived as
      aligned (Nijhawan (1994). Nature, 370, 256-257); with continuously changing
      colour, spatial frequency, pattern entropy or luminance, the flashed target
      should have feature value which changing target obtains only later (Sheth,
      Nijhawan, & Shimojo (2000). Nature Neuroscience, 3, 489-495). It was found that
      flash-lag effect is present even if the continuously accumulating pre- and post
      target input consists in spatially and featurally invariant stimulation. The
      perceptual precedence of the target in stream over its synchronous single-flashed
      replica may result from perceptual acceleration where newly arriving visual
      signals are facilitated by the locally preceding stimulation.

PMID- 11292501
TI  - Differential effect of attention to translation and expansion on motion
      aftereffects (MAE).
AB  - Recent fMRI findings have shown that selective attention to translating dots
      enhances V1 and MT complex activity whereas attention to expansion enhances MT
      complex activity rather than V1 (Watanabe et al., Proceedings of the National
      Academy of Sciences of the USA, (1998a) 95(19), 11489-11492). In order to clarify
      whether or not attention actually enhances the neural mechanism for the attended
      motion direction(s), we took advantage of the motion aftereffect (MAE), using
      superimposed groups of translating and expanding dots as the adaptation stimulus.
      During the adaptation stage, the subject was instructed to direct attention to
      one-way translation, expansion, or no particular motion or location, while gazing
      at the fixation point. The strength of the MAE in the attended monocular
      condition was greater than the sum of the unattended monocular MAE and the
      attended binocular MAE. In another experiment the monocular and binocular
      components showed linear additivity. These results suggest that attention
      enhances the monocular mechanism for the attended translational direction and
      that bottom-up monocular signals and top-down attentional signals simply add
      linearly. In contrast, no significant monocular contribution was found for
      attention to expansion. This is not only in accord with previous fMRI findings
      (Watanabe et al., 1998a), but also supports the thesis that attention to
      translation or expansion enhances the activation of the mechanism for the
      attended motion, rather than simply increasing arousal as a result of a heavier
      task load.

PMID- 11292502
TI  - Comparing increment and decrement probes in the probed-sinewave paradigm.
AB  - Using the probed-sinewave paradigm, we explore the differences between increment
      and decrement probes across a range of frequencies (approx. 1-19 Hz). In this
      paradigm, detection threshold is measured for a small test probe presented on a
      large sinusoidally flickering background (at eight different phases). Probe
      thresholds are very similar for increment and decrement probes, but there is a
      very small (and systematic) difference: increment thresholds are usually slightly
      higher relative to decrement thresholds during the part of the cycle when the
      background's intensity is increasing. Although Wilson's (1997, Vis. Neuro., 14,
      403-423) model substantially underestimates the size of this difference, it
      predicts some phase dependency. However, the existence of On- and Off-pathways in
      Wilson's model is not important for these predictions. A recent model by Snippe,
      Poot, and van Hateren (2000, Vis. Neuro., 17, 449-462) may be able to predict
      this result by using explicit contrast-gain control rather than separate On- and
      Off-pathways. Auxiliary experiments measuring the perceived polarity of the probe
      provide a further argument suggesting that separate On- and Off-pathways are not
      useful in explaining increment and decrement probe thresholds.

PMID- 11292503
TI  - Configuration specificity in bisection acuity.
AB  - Crucial for the perception of form are the spatial relationships between the
      elements of a visual stimulus. To investigate the mechanisms involved in coding
      the distance between visual stimuli, thresholds for detecting whether a central
      marker accurately bisects a spatial interval were compared for a variety of
      configurations. Thresholds are best when all three members of the bisection
      configuration are identical. Performance is impaired, often by as much as a
      factor of two, when the outer delimiters of the spatial interval differ from the
      central marker in either length, orientation or contrast polarity. Illusory
      contours act poorly as borders for bisection by a central line. Disparity
      thresholds are not affected by orientation differences between test and flanking
      lines. Because in peripheral vision bisection acuity improves with practice,
      transfer of training between configurations can be used to gauge overlap of
      neural processing mechanisms. Transfer is complete only between patterns where
      all markers are similar, reduced when the outer markers differ by 20 degrees in
      orientation and absent when they are orthogonal. The dependence of bisection
      discrimination on similarity between the elements of the stimulus demonstrates
      that the encoding of spatial location and spatial extent are coupled to the
      coding of other stimulus properties.

PMID- 11292504
TI  - The time course of the lower threshold of motion during rapid events of
      adaptation.
AB  - To examine how the time course of rapid events of adaptation affect motion
      vision, the lower threshold of motion (LTM) was measured for suprathreshold
      sinusoidal gratings in presence of transient and steady glare. In the case of the
      transient condition, glare and stimulus were presented separated in time by a
      variable extent (SOA: 50-450 ms). A two alternative forced choice paradigm using
      the method of constant stimuli was adopted to measure the LTM. It was found that
      LTM follows the characteristic Crawford's time course of adaptation. Results are
      similar for two stimulus duration (300 and 500 ms). It was proposed that the
      increment of contrast threshold for displacing gratings (C(tq)) due to the loss
      of sensitivity produced by the sudden onset of the glare source can explain the
      results.

PMID- 11292505
TI  - Express saccades: is bimodality a result of the order of stimulus presentation?
AB  - Subjects undertook a saccadic gap task, in which the fixation target is
      extinguished for a period before the appearance of the peripheral stimulus. The
      majority showed a population of short-latency express saccades in addition to the
      main, slower, distribution. However, closer analysis showed that nearly all of
      this bimodality was due to the order in which trials were performed: the faster
      responses came almost entirely from trials in which the target was on the
      opposite side from the preceding trial, slower ones when it was on the same side.
      Further experiments using a novel two-gap task demonstrated that this inter-trial
      effect is due to the return eye movement of one trial conditioning the first
      saccade of the next. Consequently, in a two-gap task the latency of the second
      saccade falls into the faster category if it is in the same direction as the
      immediately preceding one: this may be the result of the oculomotor system
      predicting target direction, saccades in the expected direction having a shorter
      latency. It seems therefore that the bimodality is not primarily the result of
      some kind of randomising process within the oculomotor system: rather, it is a
      consequence of the way in which saccadic experiments are normally conducted.

PMID- 11292506
TI  - On the psychophysics of the shape triangle.
AB  - We earlier introduced an approach to categorical shape description based on the
      singularities (shocks) of curve evolution equations. We now consider the simplest
      compositions of shocks, and show that they lead to three classes of
      parametrically ordered shape sequences, organized along the sides of a shape
      triangle. By conducting several psychophysical experiments we demonstrate that
      shock-based descriptions are predictive of performance in shape perception. Most
      significantly, the experiments reveal a fundamental difference between perceptual
      effects dominated by when shocks form with respect to one another, versus those
      dominated by where they form. The shock-based theory provides a foundation for
      unifying tasks as diverse as shape bisection, recognition, and categorization.

PMID- 11292507
TI  - A principal component analysis of facial expressions.
AB  - Pictures of facial expressions from the Ekman and Friesen set (Ekman, P.,
      Friesen, W. V., (1976). Pictures of facial affect. Palo Alto, California:
      Consulting Psychologists Press) were submitted to a principal component analysis
      (PCA) of their pixel intensities. The output of the PCA was submitted to a series
      of linear discriminant analyses which revealed three principal findings: (1) a
      PCA-based system can support facial expression recognition, (2) continuous two
      dimensional models of emotion (e.g. Russell, J. A. (1980). A circumplex model of
      affect. Journal of Personality and Social Psychology, 39, 1161-1178) are
      reflected in the statistical structure of the Ekman and Friesen facial
      expressions, and (3) components for coding facial expression information are
      largely different to components for facial identity information. The implications
      for models of face processing are discussed.

PMID- 11292508
TI  - Opsoclonus-induced occipital deactivation with a region-specific distribution.
AB  - The cerebral distribution of 2-[18F]fluoro 2-deoxy-D-glucose (FDG) uptake in a
      patient with opsoclonus was measured by positron emission tomography (PET) and
      subsequently compared with the distribution in ten normal subjects. Statistical
      parametric mapping (SPM) revealed a decreased occipital FDG uptake in the
      patient, particularly at the posterior bank of the parieto-occipital sulcus
      (putative visual area PO/V6), in the region ventrally bordering V5, and
      anterolaterally in the calcarine sulcus. Such a specific pattern of occipital
      deactivation may indicate that opsoclonus suppresses the processing of visual
      motion along the magnocellular pathway. This is in agreement with normal saccadic
      suppression which has been proposed to contribute to the perception of a stable
      visual space.

PMID- 11292509
TI  - Chromatic and achromatic defects in patients with progressing glaucoma.
AB  - To evaluate the pattern of losses associated with glaucomatous injury in patients
      with progressing glaucoma, functional losses were examined in 14 patients with
      progressing glaucoma using tests for which detection should be selectively
      mediated by one of three psychophysical mechanisms. Red-on-white increments, blue
      on-white increments and critical flicker frequency were used to isolate the
      responses of the red-green chromatic mechanism, the blue-on chromatic mechanism,
      and the high-frequency flicker achromatic mechanism. For our 3.1 degrees circular
      stimuli, chromatic defects were found in a greater number of the patients with
      glaucoma than were achromatic defects. We evaluated these defects in terms of two
      existing hypotheses: preferential loss and reduced redundancy. The greater
      sensitivity to glaucomatous injury of chromatic tests, compared to achromatic
      tests, found in this and other studies and the apparent discrepancy between
      anatomical and psychophysical studies can be parsimoniously explained by
      differences in cortical summation of ganglion cell responses for the chromatic
      and achromatic pathways.

PMID- 11292510
TI  - The influence of tinted lenses upon ocular accommodation.
AB  - We determined the effect upon accommodative responses of tinted lenses prescribed
      for the relief of visual discomfort in a group of five long term lens wearers.
      Static and dynamic responses were measured under four viewing conditions (1)
      prescribed tinted lens (2) neutral density filter (3) tinted lens of
      complementary colour and (4) no absorptive lens. While similarity and normality
      of the mean stimulus-response functions between the four viewing conditions were
      evident, the low frequency component of the accommodation microfluctuations was
      significantly greater while viewing the target in the 'no lens' viewing
      condition. These increases in the low frequency components (LFC) of the
      accommodation may be a subtle indicator of visual stress in these patients.
      Colour specificity is not supported by this finding.

PMID- 11292511
TI  - Immunogenetics of longevity. Is major histocompatibility complex polymorphism
      relevant to the control of human longevity? A review of literature data.
AB  - Literature data suggest that human longevity may be directly correlated with
      optimal functioning of the immune system. Therefore, it is likely that one of the
      genetic determinants of longevity resides in those polymorphisms for the immune
      system genes that regulate immune responses. Accordingly, studies performed on
      mice have suggested that the Major Histocompatibility Complex (MHC), known to
      control a variety of immune functions, is associated with the life span of the
      strains. In the last 25 years, a fair number of cross-sectional studies that
      searched for the role of HLA (the human MHC) genes on human longevity by
      comparing HLA antigen frequencies between groups of young and elderly persons
      have been published, but conflicting findings have been obtained. In fact, the
      same HLA antigens are increased in some studies, decreased in others and
      unchanged in others. On the whole, that could lead us to hypothesize that the
      observed age-related differences in the frequency of HLA antigens are due to
      bias. In our opinion, this hypothesis is real for most studies owing to major
      methodological problems. However, some studies that do not meet these biases have
      shown an association between longevity and some HLA-DR alleles or HLA-B8,DR3
      haplotype, known to be involved in the antigen non-specific control of immune
      response. Thus, HLA studies in man may be interpreted to support suggestions
      derived from the studies on congenic mice on MHC effects on longevity. However,
      in mice the association may be by way of susceptibility to lymphomas whereas, in
      human beings, the effect on longevity is likely, via infectious disease
      susceptibility. Longevity is associated with positive or negative selection of
      alleles (or haplotypes) that respectively confer resistance or susceptibility to
      disease(s), via peptide presentation or via antigen non-specific control of the
      immune response.

PMID- 11292512
TI  - Long-live euthymic BALB/c-nu mice. I. Survival study suggests body weight as a
      life span predictor.
AB  - This paper is the first of a series aimed to show the main physiological and
      pathological characteristics of male euthymic BALB/c-nu mice, a long-live strain
      of BALB/c mice bred in our own Institute. In particular, the first two paired
      papers are respectively devoted to general survival information and disease
      characteristics, also taking into account very old animals that are of high
      interest for studies on successful aging. In this paper we report the analysis of
      survival kinetics, the time course of body weight and the correlation between
      body weight and time-at-death. The longitudinal study has been performed on 88
      male mice, checking individually their body weight and date of death and
      analyzing survival data by a model built by our own. Survival analysis shows
      quite higher longevity (median age: about 29 months) in this population when
      compared with other BALB/c strains. The most relevant finding on body weight is
      its correlation with longevity until the age of 22 months: thinner subjects live
      longer and lose weight at a lower rate than their heavier mates. Results have
      formed the basis on which to plan the cross-sectional experiment to study
      pathologies and biological parameters at different ages, including a group of
      mice at very advanced ages (34 months).

PMID- 11292513
TI  - Long-live euthymic BALB/c-nu mice. II: spontaneous tumors and other pathologies.
AB  - This paper is the second of a series aimed to show the main physiological and
      pathological characteristics of male euthymic BALB/c-nu mice, a long-live strain
      of BALB/c mice bred in our own Institute. The previous paired paper Piantanelli
      (Mech. Ageing Dev. (2001)) has been devoted to a survival study up to advanced
      ages highly interesting for studies on successful aging. In the present paper we
      report first data of a cross-sectional study on 4,15,22,28 and 34 months-old
      mice, dealing with tumors and other relevant pathologies. Results have shown that
      tumors or other pathologies can hardly be detected up to the age of 22 months. At
      34 months of age about 40% of mice revealed a variety of neoplasia and other
      diseases are clearly detectable. These results suggest that a significant
      increase in longevity could be a factor increasing the risk of tumor development;
      thus, caution has to be paid in studies on mice utilized for long term
      carcinogenicity assay, where animals are sacrificed at the age of 18 months,
      according to the International Program. Finally, animals of the same
      chronological age have been subdivided in clusters according to their presumptive
      longevity, estimated taking advantage of the relationship between body weight and
      age-at-death found in the paired longitudinal study. This subdivision will be
      helpful in interpreting inter-individual variability of the biological parameters
      checked in these animals.

PMID- 11292514
TI  - Effects of L-phenylalanine on acetylcholinesterase and Na(+), K(+)-ATPase
      activities in adult and aged rat brain.
AB  - The effect of different L-phenylalanine (Phe) concentrations (0.12-1.8 mM) on
      acetylcholinesterase (AChE), (Na(+), K(+))-ATPase and Mg(2+)-ATPase activities
      was investigated in homogenates of adult and aged rat whole brain at 37 degrees
      C. Adult and aged rat experiments were necessary in relation to phenylketonuria
      (PKU) since phenylketonuric patients usually discontinue their therapeutic
      special diet when they reach adulthood. Diet discontinuation results in the
      pathological increase of Phe concentration in plasma and consequently in brain.
      AChE activity in adult brain homogenates showed a decrease up to 18% (P<0.01)
      with 0.48--1.8 mM Phe preincubated for 1 h. Adult brain Na(+), K(+)-ATPase was
      stimulated by 30--35% (P<0.01) in the presence of 0.48--1.8 mM Phe. However, high
      Phe concentrations were not able to affect the activities of AChE and Na(+), K(+)
      ATPase, when preincubated with aged brain homogenate for 3 h. Moreover, high Phe
      concentrations appeared unable to affect the activity of eel E. electricus pure
      AChE inhibited about 30% (P<0.001) by the free radical system H(2)O(2)/Fe(2+).
      Also, the antagonists of alpha- and beta-adrenergic receptors (phenoxybenzamine
      and propranolol, respectively) inhibited adult rat brain Na(+), K(+)-ATPase
      activity about 30--40% (P<0.01) and Phe was unable to change this action. It is
      suggested that: (a) The inhibitory effect of Phe on brain AChE and its
      stimulatory effect on brain Na(+), K(+)-ATPase are decreased with age; (b) These
      effects may be influenced by aging factors, such as free radical action and/or
      reduced density of alpha- and beta-adrenergic receptors in the tissue.

PMID- 11292515
TI  - Unitary or binary nature of classification of depressive illness and its
      implications for the scope of manic depressive disorder.

PMID- 11292516
TI  - Attention deficit hyperactivity disorder with bipolar disorder in girls: further
      evidence for a familial subtype?
AB  - BACKGROUND: To clarify the nosologic status of girls with attention deficit
      hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar
      disorder (BPD). METHODS: Using blind raters and structured psychiatric
      interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their
      786 first degree relatives. Analyses tested specific hypotheses about the
      familial relationship between ADHD and bipolar disorder in girls. RESULTS: After
      stratifying our ADHD sample into those with and without BPD, we found that: (1)
      relatives of both ADHD subgroups were at significantly greater risk for ADHD than
      relatives of non-ADHD controls, (2) the two subgroups did not significantly
      differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar
      disorder was observed among relatives when the proband child had BPD but not ADHD
      alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no
      evidence of a trend for random mating between ADHD parents and those with mania.
      LIMITATIONS: Limitations of this study include the lack of direct interviewing of
      probands and the limited number of ADHD/BPD probands available. CONCLUSIONS:
      These findings extend to girls what was previously documented in boys and suggest
      that comorbid ADHD with BPD in girls is familially distinct from other forms of
      ADHD and may be related to what others have termed childhood onset BPD. Future
      work could determine if this subgroup has a characteristic course, outcome and
      response to treatment.

PMID- 11292517
TI  - The relatively good prognosis of bipolar disorders in a Turkish bipolar clinic.
AB  - BACKGROUND: Bipolar affective disorder is considered to be a disabling illness
      with a relapsing and remitting course resulting in enduring psychosocial
      consequences. In this study, we aimed to determine the demographic and clinical
      characteristics of patients with bipolar illness, types of treatment at inpatient
      and outpatient settings and their outcome. METHOD: Life charts of 61 bipolar
      outpatients and hospital charts of 47 manic inpatients were retrospectively
      evaluated regarding the demographics, course of illness and the treatment at both
      settings. RESULTS: 82.5% of the outpatients were euthymic and 42.5% were on
      lithium monotherapy at the time of investigation. Psychosocial adjustment was
      good. High level of education and marital status affected compliance positively.
      In the outpatient group, 24.2% were bipolar 2 (BP-II): they differed from bipolar
      1 (BP-I) patients in having a higher number of lifetime episodes. Females
      outnumbered males in both settings, 11 had suffered higher numbers of previous
      episodes, as well as longer stays in hospital. Lithium was the most commonly used
      agent in acute mania (78.7%); 89.4% of the inpatients received combination
      treatment, mainly a mood stabilizer with a neuroleptic. Adjunctive neuroleptics
      decreased from 82.4 to 56.7% after 1995: This resulted in longer lengths of stay
      in hospital. LIMITATIONS: Data were collected naturalistically in a non-blind
      fashion. CONCLUSION: Lithium is still the leading mood stabilizer of choice for
      the acute and maintenance phases of bipolar disorder in our patient population.
      We submit that family support, high levels of education as well as an in-depth
      follow-up represented the contributory factors in the good overall outcome.

PMID- 11292518
TI  - Subjective response to and tolerability of long-term supraphysiological doses of
      levothyroxine in refractory mood disorders.
AB  - BACKGROUND: Although supplementation with supraphysiological doses of
      levothyroxine (T4) has been an effective treatment for refractory affective
      disorders in open studies, questions remain as to the tolerability of this
      treatment. This is the first study to investigate subjective patient response and
      tolerability to long-term treatment with adjunctive T4. METHODS: Of 24 patients
      with refractory affective disorders or schizoaffective disorder who were
      consecutively included into an open trial with supraphysiological T4, 16 were
      eligible for this study. Four measures were used to rate tolerability to T4
      treatment. Subjective response was graded on a scale ranging from -33 (maximal
      negative response) to +33 (maximal positive response). Positive and negative
      effects were assessed on a structured questionnaire. Clinical tolerance was
      assessed with the clinician-rated Thyroid Symptom List and the self-rated Von
      Zerssen Complaint Lists. Outcome was assessed with the CGI for prophylactic
      ratings (CGI-BP). RESULTS: At the time of assessment, patients had been treated
      with supraphysiological T4 (mean dose 368 microg/d) for a mean of 54 months. The
      total subjective response score was +25.2. Positive subjective response and
      observer-rated treatment success were moderately correlated. Ratings on the
      Thyroid Symptom List indicated an overall favorable side effect profile. General
      physical and mental symptoms were only slightly higher than in the general
      population. LIMITATIONS: This was an open, cross-sectional study that only
      included responders and partial responders to T4 treatment. CONCLUSIONS:
      Subjective response and side-effect tolerability of long-term supraphysiological
      doses of T4 is favorable in patients with refractory mood and schizoaffective
      disorders who respond to the intervention.

PMID- 11292519
TI  - Antioxidative enzyme activities and lipid peroxidation in major depression:
      alterations by antidepressant treatments.
AB  - BACKGROUND: Reactive oxygen species (ROS) may play a role in some
      neuropsychiatric disorders. There is some evidence that the activation of immune
      inflammatory process, increase of monoamines catabolism, and abnormalities in
      lipid compounds may cause overproduction of ROS and, in turn, antioxidative
      enzyme activities (AEAs) and lipid peroxidation (LP), and that these phenomena
      may be related to pathophysiology of major depression. METHODS: The aims of this
      study were (i) to examine the AEAs and LP levels of the major depressed (MD)
      patients, and to compare these with healthy controls; and (ii) to investigate the
      effect of subchronic treatment with selective serotonin reuptake inhibitors
      (SSRIs) on AEAs and LP levels in MD subjects. Thirty MD patients, and 32 healthy
      controls (HC) participated in this study. AEAs and LP levels were determined by
      measuring several antioxidative enzymes and malondialdehyde (MDA) levels in
      plasma and/or in red blood cells. RESULTS: Major depressed patients, especially
      melancholic patients, had higher AEA and LP levels than those of healthy
      controls. After treatment for 3 months with SSRIs, AEA and LP levels of the
      patients were significantly decreased to normal levels. CONCLUSION: These
      findings suggest that (i) major depression, especially with melancholia, is
      associated with elevated AEAs and LP, and that (ii) subchronic treatment with
      SSRIs may have a suppressive effect on AEA and LP. CLINICAL IMPLICATION AND
      LIMITATION: AEAs might be used for monitoring SSRIs effects.

PMID- 11292520
TI  - Exploring the relationship between different psychosocial determinants of
      depression: a multidimensional scaling analysis.
AB  - BACKGROUND: The psychological literature concerned with the aetiology and
      maintenance of depression has generally been considered too diverse to allow for
      integration of concepts into a single comprehensive review. Moreover, there is
      little understanding of the original theorists' conceptualisation of the key
      themes underlying psychosocial theories of depression. This study aims to create
      a single framework of psychosocial depression concepts based on the opinions of
      key original theorists. METHOD: A quantitative integration of depression factors
      was conducted. Ninety-nine factors were identified from 27 theories. Fourteen of
      the original theorists sorted the factors into groups using a card sort task.
      RESULTS: Three-way multidimensional scaling (MDS) produced a four-dimensional
      solution with high explained variance and low stress. Dimension one describes
      cognitions resulting in a lack of positive intrapersonal and interpersonal
      communication. Dimension two emphasises behaviours and the impact of
      environmental stressors. Dimension three describes the individual's pursuit of
      unrealistic goals and a perceived lack of control. Finally, Dimension four
      describes concepts relating to self-focus and self-reinforcement. LIMITATIONS:
      future research could examine clinicians and depressed individuals'
      understandings of the literature. CONCLUSIONS: the MDS solution identifies the
      original theorists' collective understanding of the literature. Clinicians could
      usefully employ the framework to identify the underlying psychosocial themes
      involved in depression. Moreover the study highlights the need for clinicians to
      consider the relationships between different conceptual areas in order to
      challenge the chronic nature of the depressive experience and the high rates of
      relapse.

PMID- 11292521
TI  - Suicidal ideation among medical students and young physicians: a nationwide and
      prospective study of prevalence and predictors.
AB  - BACKGROUND: Despite an increased risk of suicide among physicians we lack studies
      on prevalence and predictors of suicidal ideation among medical students and
      young doctors. METHOD: A prospective study of Norwegian medical students (n=522)
      re-examined after the first postgraduate year, comprising suicidal thoughts and
      attempts, perceived study stress, job stress, and personality. RESULTS: The
      previous year prevalence of suicidal thoughts was 14% at both points of time. The
      lifetime prevalence was 43%, while 8% had planned suicide, and 1.4% had attempted
      suicide. Suicidal ideation in medical school was predicted by lack of control,
      personality trait, single marital status, negative life events and mental
      distress (anxiety and depression). In the first postgraduate year, mental
      distress was the most important predictor, but before controlling for this
      variable, job stress, vulnerability (neuroticism), single status, and less
      working hours were independent predictors. Prospectively, suicidal thoughts and
      vulnerability as student predicted postgraduate suicidal ideation. CONCLUSIONS:
      The level of suicidal thoughts was high, but the level of attempts was low.
      CLINICAL IMPLICATIONS: Preventive efforts should be directed both at the
      students' abilities to cope with stress and at mental health services for young
      doctors. LIMITATIONS OF STUDY: The lower response rate at follow-up (57%) may
      reduce external validity.

PMID- 11292522
TI  - Does pretreatment anxiety predict response to either bupropion SR or sertraline?
AB  - BACKGROUND: A common clinical belief is that more sedating and/or serotonin
      selective antidepressants are preferred for depressed patients with symptoms of
      anxiety compared with more activating and/or catecholamine-selective
      antidepressants. The purpose of this study was to determine whether higher
      baseline anxiety is associated with different antidepressant responses to
      bupropion sustained release (SR) or sertraline. METHODS: A retrospective data
      analysis was conducted using pooled data from two identical 8-week, randomized,
      double-blind, placebo-controlled multicenter studies of bupropion SR (n=234),
      sertraline (n=225), and placebo (n=233) in adult outpatients with recurrent,
      major depressive disorder. Anxiety symptoms were measured using the 14-item
      Hamilton Anxiety Rating Scale scores. RESULTS: Baseline anxiety levels were not
      related to antidepressant response to treatment with either bupropion SR or
      sertraline, nor did they differentiate between responders to bupropion SR and
      responders to sertraline. CONCLUSIONS: Baseline anxiety levels do not appear to
      be a basis for selecting between bupropion SR and sertraline in the treatment of
      outpatients with major depressive disorder.

PMID- 11292523
TI  - The Seasonal Health Questionnaire: a preliminary validation of a new instrument
      to screen for seasonal affective disorder.
AB  - BACKGROUND: The main screening tool for Seasonal Affective Disorder (SAD) is the
      Seasonal Pattern Assessment Questionnaire, but its reliability and validity have
      been thrown into doubt by several studies. METHOD: In this study we developed a
      new questionnaire, the Seasonal Health Questionnaire (SHQ), which is scored by
      computer to derive the four main operational criteria for diagnosis of SAD. A
      group of clinically diagnosed SAD patients was contrasted with a group of
      patients with recurrent non-seasonal depressive disorder using the SPAQ and the
      SHQ. RESULTS: The SHQ could be completed without difficulty by patients with long
      histories of recurrent mood disorder. The SPAQ and the Rosenthal Criteria were
      the least specific of the criteria for identifying SAD - misclassifying many non
      seasonal patients. CONCLUSIONS: After further development the SHQ may be a more
      appropriate screening instrument for SAD. The SPAQ should no longer be used for
      this purpose as it gives misleadingly high estimates of prevalence.

PMID- 11292524
TI  - Loss of response to antidepressants and subsequent refractoriness: diagnostic
      issues in a retrospective case series.
AB  - BACKGROUND: The loss of response to antidepressant drugs is not an uncommon
      phenomenon. While some patients respond to changes in the drug regimen, others
      develop resistance to various treatment modalities. METHOD: I describe 15 cases
      who had a loss of response to repeated trials of antidepressants before
      developing a chronic and severe, refractory depression. RESULTS: These patients
      had failed to respond to various treatment strategies including substitution with
      other antidepressant drugs, augmentation with agents such as T3 and lithium; and
      finally electroconvulsive therapy (ECT). Following discontinuation of
      antidepressants and treatment with mood stabilizers, there was a sustained
      improvement. Notably some of the patients who had earlier failed to respond to
      mood stabilizers in combination with unimodal antidepressants improved upon
      discontinuation of antidepressants and continued treatment with mood stabilizers.
      LIMITATIONS: Open trial, retrospective design and small sample size. CONCLUSION:
      These clinical findings suggest that some refractory depressives represent
      cryptic bipolar disorders. Prospective validation is necessary to support this
      conclusion.

PMID- 11292525
TI  - Characterization of caprine interleukin-4.
AB  - Caprine interleukin-4 (IL-4) cDNA was cloned from RNA of mitogen stimulated goat
      peripheral blood mononuclear cells utilizing reverse transcriptase-polymerase
      chain reaction. The sequence of caprine IL-4 cDNA corresponds to a 535 nucleotide
      mRNA with 5'- and 3'-untranslated regions and a 405 nucleotide open reading
      frame, the first 66 nucleotides of which encode a putative signal peptide. Mature
      IL-4 is a 12.8kDa protein containing six cysteine residues and two potential N
      linked glycosylation sites and is highly homologous with other ruminant IL-4. The
      predicted molecular mass of mature unglycosylated IL-4 was confirmed by western
      blot of recombinant caprine IL-4 expressed in bacteria with a monoclonal antibody
      against a carboxyterminal peptide derived from the predicted amino acid sequence
      of bovine IL-4. Eukaryotic expression plasmids containing caprine IL-4 cDNA were
      used to characterize recombinant IL-4. Transcription of IL-4 mRNA was confirmed
      by transfection of COS-7 and goat synovial membrane cells, and recombinant IL-4
      produced by stably transfected L929 cells inhibited inducible nitric oxide
      synthase in macrophages. Genetic immunization of mice with a caprine IL-4 cDNA
      expression plasmid induced antibodies against recombinant caprine IL-4 produced
      in bacteria.

PMID- 11292526
TI  - Characterization and cloning of a major high molecular weight house dust mite
      allergen (Der f 15) for dogs.
AB  - Although house dust mites (HDM(s)) are important elicitors of canine allergy, the
      low molecular weight molecules defined as major allergens for humans do not
      appear to be major allergens for dogs. Western blotting of Dermatophagoides
      farinae (D. farinae) extracts with sera from sensitized dogs showed that the
      majority of animals had IgE antibodies specific for two proteins of apparent
      molecular weights of 98 and 109kDa (98/109kDa). The N-terminal sequences of these
      two proteins were identical, suggesting they were very closely related, and
      sequencing of internal peptides showed the protein(s) to have homology with
      insect chitinases. A purified preparation of 98/109kDa proteins elicited positive
      intradermal skin tests (IDST(s)) in a group of well-characterized atopic dogs
      sensitized to D. farinae, but not in normal dogs. A rabbit polyclonal antiserum
      raised against the purified proteins was used to immunoscreen a D. farinae cDNA
      library. The mature coding region of the isolated chitinase cDNA predicts a
      protein of 63.2kDa; sequence analysis and glycan detection blotting suggest that
      the molecule is extensively O-glycosylated. Monoclonal antibodies made against
      the purified native protein were used to localize the chitinase in sections of
      whole D. farinae mites. The protein displayed an intracellular distribution in
      the proventriculus and intestine of the mite, suggesting that it has a digestive,
      rather than a moulting-related, function. The high prevalence of IgE antibodies
      to this antigen in canine atopic dermatitis makes it a major HDM allergen for
      dogs, and the protein has been formally designated Der f 15.

PMID- 11292527
TI  - The P2X7 purinergic receptor on bovine macrophages mediates mycobacterial death.
AB  - P2X7 is an ATP gated purinoceptor that has been linked to various immune
      responses. P2X7 appears to be expressed ubiquitously in the immune system and
      thus may be important as an effector pathway or play significant roles in cell
      activation/death. 2',3'-(4-Benzoyl)benzoyl ATP is the most potent agonist of this
      receptor and ATP in its fully dissociated form (ATP(4-)) also activates the
      receptor. High concentrations of ATP can cause the P2X7 receptor to induce pore
      formation on the surface of the cell that allows molecules of considerable size
      to pass and can lead to cell death. The P2X7 receptor has also been linked to
      various immune activities when the concentration of ATP is lower, including the
      release of IL-1beta. The role P2X7 receptors have on immune cell activities is
      just beginning to be understood. We sought to determine the role of P2X7 on
      bovine macrophages in eliminating the causative agent of bovine-type
      tuberculosis, Mycobacterium bovis. Because high concentrations of ATP are linked
      to macrophage death, we determined if this method of cell destruction also leads
      to reduced bacterial viability. We find that P2X7 is present on bovine
      macrophages from different sources, including both peripheral blood-derived as
      well as alveolar macrophages. In addition, P2X7 mRNA is present in B and T
      lymphocytes. The treatment of M. bovis-infected macrophages with ATP results in
      reduced macrophage viability as well as reduced M. bovis viability.

PMID- 11292528
TI  - Bacterially induced activation of interleukin-18 in porcine intestinal mucosa.
AB  - Interleukin (IL)-18 is a cytokine with structural and functional properties
      similar to IL-1beta and IL-12, respectively. It is activated by caspase-1
      cleavage, like IL-1beta, and induces interferon (IFN)-gamma, like IL-12. In order
      to study the role of IL-18 in the immune response to infectious diseases of
      mucosal surfaces we cloned and expressed porcine IL-18 and developed antibodies
      to the protein. Porcine IL-18 retains the caspase-1 cleavage site present in
      other mammalian IL-18 proteins, but has two potential N-linked glycosylation
      sites not found in those proteins. Porcine interleukin-18 mRNA and protein are
      expressed in immune tissues including lymph nodes and gut associated lymphoid
      tissues. Specific cell types containing IL-18 include lung and splenic
      macrophages, nonadherent spleen cells and intestinal epithelial cells. Although
      IL-18 transcription is moderately induced by lipopolysaccharide, the magnitude
      and total expression level are small compared to those of interleukin-1beta. In
      vivo and ex vivo infection of intestinal mucosa with Salmonella choleraesuis
      resulted in a decrease in size of IL-18, consistent with cleavage of the
      preprotein by caspase-1. Thus, IL-18 is present in mucosal tissues where it could
      play a role in the immune response to invading pathogens.

PMID- 11292529
TI  - Thymidine utilization abnormality in proliferating lymphocytes and hepatocytes of
      the woodchuck.
AB  - Effective incorporation of tritiated thymidine ([(3)H]TdR) into proliferating
      lymphocytes is important because [(3)H]TdR is a standard label to study
      proliferate T-cell responses. We analyzed the thymidine utilization of woodchuck
      peripheral blood lymphocytes (PBL) since the [(3)H]TdR incorporation assay was
      not applicable to measure proliferative immune responses in the woodchuck, a
      current major virus/host model for human hepatitis B virus infection.
      Incorporation of [(3)H]TdR into DNA as well as the activity of the salvage
      pathway enzyme thymidine kinase (TK) of proliferating woodchuck PBL was low
      compared to human lymphocytes. Furthermore, [(3)H]TdR incorporation of
      proliferating woodchuck PBL remained residual regardless of the use of
      methotrexate, an inhibitor of the competitive deoxythymidine monophosphate de
      novo synthesis pathway. Using a human probe, specific for the proliferation
      associated TK1, we proved the genomic presence and transcription of TK1 sequences
      in various species. TK1 sequences were detected in the genome of human, mouse,
      woodchuck, and chicken specimens. In contrast to proliferating human PBL and 3T3
      mouse fibroblasts, no TK1 transcript was found in proliferating woodchuck PBL and
      hepatic cells. Transfection experiments with vectors containing the murine or
      human TK1 and selection assays demonstrated the ability of woodchuck cells to
      transcribe TK1 and to express functional TK1 proteins. Our study characterizes
      the unique failure of sufficient [(3)H]TdR incorporation into proliferating
      woodchuck cells and demonstrates tritiated adenine and serine as alternative
      labels to monitor PBL proliferation in the woodchuck.

PMID- 11292530
TI  - Immune response in hormonally-induced prostatic hyperplasia in the dog.
AB  - We induced prostatic enlargement in castrated dogs using either androgen alone or
      androgen combined with estrogen. In addition to previously reported hyperplastic
      changes, marked infiltration with immune effector cells was observed. This
      mononuclear cell infiltrate was phenotypically characterized using CD3 as pan T
      lymphocyte marker, CD79 for B-lymphocytes, MAC378 for macrophages, and antibodies
      against kappa- and lambda-immunoglobulin (Ig) light chains for plasma cells. The
      majority of inflammatory cells (>80%) in the mononuclear infiltrates were T
      lymphocytes and the numbers correlated with the degree of inflammation. The B
      lymphocytes were found particularly in areas with marked follicular formation and
      diffuse infiltration, whereas there were only a few positive cells (<10%) in
      areas with a moderate or slight inflammation. Macrophages were found primarily in
      areas with atrophic and cystic changes with and without inflammation. The
      expression of lambda-Ig-positive cells depended on the degree of inflammation (5
      10%), whereas immunoreactivity of kappa-Ig did not correlate with the extent of
      inflammatory reaction. Our present findings together with the evaluation of
      longitudinal biopsies of hormonally-induced BPH indicate that hyperplasia
      preceded cell-mediated and humoral immune response.

PMID- 11292531
TI  - Cytokine mRNA levels in isolated feline monocytes.
AB  - Real-time PCR systems were developed to quantitate cytokine expression in short
      time cultivated feline monocytes. Feline-specific interleukin-1beta (IL-1beta),
      IL-6, and tumor necrosis factor-alpha (TNF-alpha) primers as well as TaqMan
      probes were designed and were adapted to a quantitative PCR system which had been
      previously established for feline IL-10 and IL-12 p40. Quantitative analysis of
      cytokine messenger RNA (mRNA) transcription based on the comparison of the
      cytokine with the housekeeping gene feline glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), providing universally expressed mRNA. GAPDH mRNA was
      readily detectable in cDNA prepared from short-time cultivated peripheral blood
      monocytes. Cytokine mRNA was demonstrated in all samples at variable amounts. IL
      1beta and TNF-alpha mRNA was constitutively expressed whereas IL-6, IL-10 and IL
      12 p40 mRNA was generally expressed at a lower level and was occasionally not
      detected. There was a great variability of cytokine production between individual
      cats and at different time points in the same cat.

PMID- 11292532
TI  - Characterisation of the kappa light chain of the brushtail possum (Trichosurus
      vulpecula).
AB  - Two full length cDNA sequences encoding the kappa light chain of the Australian
      marsupial, Trichosurus vulpecula, the brushtail possum, were isolated from a
      mesenteric lymph node cDNA library. The constant regions (Ckappa) of the two
      light chains were identical, but the variable (Vkappa) and joining (Jkappa)
      regions were different. At the amino acid level, possum Ckappa was most similar
      to Ckappa of an American marsupial, Monodelphis domestica (75%), with similarity
      to eutherian Ckappa ranging from 47 to 63%. The availability of molecular data
      will enable the development of immunological reagents for studying immune
      responses and disease in marsupials, thereby aiding conservation strategies and
      veterinary medicine.

PMID- 11292533
TI  - An accessory role for the diacylglycerol moiety of variable surface glycoprotein
      of African trypanosomes in the stimulation of bovine monocytes.
AB  - The membrane-associated form of the variable surface glycoprotein (mfVSG) from
      African trypanosomes is a potent macrophage activator capable of inducing
      production of tumor necrosis factor alpha (TNFalpha) in both bovine and murine
      models. Using a bovine model, we have re-investigated the hypothesis that the
      diacylglycerol moiety of the glycosylphosphatodylinositol (GPI) anchor is
      involved in macrophage activation and might be the actual parasite toxin. The
      anchor of the variable surface glycoprotein (VSG) was labeled with (3)H-myristic
      acid and VSG purified in its membrane-associated form. The dimyristylglycerol
      moiety of the anchor was released by phospholipase C cleavage. Integrity of the
      anchor and efficiency of cleavage was verified by autoradiography and
      methanol:hexane extraction. For analysis of biological function, bovine monocytes
      were used which had been incubated with bovine interferon gamma (primed) or with
      culture medium (unprimed). The VSG purified in its membrane-associated form was
      found to stimulate both primed and unprimed cells to secrete TNFalpha. The same
      preparation from which the dimyristylglycerol moiety had been cleaved was no
      longer able to stimulate unprimed cells but could still stimulate primed cells.
      Our data indicate that the presence of the dimyristylglycerol is not an absolute
      requirement for induction of TNFalpha production but can substitute for the
      interferon gamma priming. Therefore, we favor the hypothesis that stimulation of
      macrophages to secrete TNFalpha by the mfVSG is mediated by an as yet unknown
      trigger moiety and is facilitated by the dimyristylglycerol anchor.

PMID- 11292534
TI  - Molecular cloning and sequencing of canine T-cell costimulatory molecule (CD28).
AB  - T-cells express CD28 and CTLA-4, and through binding to their shared ligands
      (CD80/CD86) on antigen presenting cells, provide a potent co-stimulatory signal
      for T-cell activation and proliferation. To investigate the role of CD28 in
      canine immune system, we hereby report the molecular cloning and sequencing of
      the full-length complementary DNA (cDNA) coding for canine CD28, from pokeweed
      mitogen stimulated canine peripheral blood lymphocytes. The cloned cDNA contains
      an open reading frame of 663 nucleotides, encoding for a polypeptide of 221 amino
      acids. The amino acid sequence of the canine CD28 showed 91.9, 80, and 79.6%
      similarities with those of the cat, cattle, and human counterparts, respectively.
      Five sequence motifs of TATT or ATTTA involved in the regulation of gene
      expression by influencing mRNA stability are found in the 3' untranslated region.
      The hexapeptide motif (MYPPPY), five cysteine residues, a potential N
      glycosylation site and a cytoplasmic phosphatidylinositol 3-kinase binding site
      in canine CD28 molecule are completely conserved in canine CTLA-4. The
      availability of full length canine CD28 will provide a useful molecule for
      studying its role in dog immune system.

PMID- 11292535
TI  - Measurement of canine IgE using the alpha chain of the human high affinity IgE
      receptor.
AB  - In vitro assays for allergen specific immunoglobulin E (IgE) are a convenient and
      reproducible alternative to intradermal skin testing in dogs. Such tests may be
      used to support a diagnosis of atopic dermatitis and to define appropriate
      allergens for immunotherapy. Current in vitro assays rely upon monoclonal or
      polyclonal antibodies as IgE detection reagents. However, in sera where allergen
      specific IgG occurs in great excess, any IgE:IgG cross-reactivity of the
      detection reagent may result in lowered assay specificity. Therefore, we have
      developed an assay for canine IgE which uses a recombinant form of the
      extracellular part of the alpha chain of the human high affinity IgE receptor
      (FcvarepsilonRIalpha). Biotinylated FcvarepsilonRIalpha shows no significant
      binding to purified canine IgG, and recognizes a heat labile antibody in serum,
      with a detection limit of 73-146pg/ml. Comparison of assay signals using the
      labeled FcvarepsilonRIalpha and a highly specific anti-canine IgE monoclonal
      antibody (MAb) shows good agreement. The FcvarepsilonRIalpha is therefore a
      sensitive and specific alternative to polyclonal or monoclonal antibodies for
      canine serum IgE measurement.

PMID- 11292537
TI  - The effect of structural QSAR parameters on skin penetration.
AB  - The permeability coefficients (log kp) of solutes through stratum corneum have
      been previously related to the octanol-water partition coefficients (log Poct)
      and solvatochromic parameters. In this study, permeation coefficient data are
      related to the theoretical chemistry-derived structural parameters and also
      molecular connectivity and molecular shape indices. The results show that these
      parameters are comparable with the solvatochromic parameters in correlation with
      log kp. Log Poct can be corrected by the theoretical parameters to explain
      permeation coefficients and the equilibrium distribution of compounds between the
      stratum corneum and water (log Km). Diffusion estimated from the expression
      log(D/h)=log kp-log Km, where D is the diffusion coefficient and h is the path
      length for diffusion was also analyzed successfully by the structural parameters.

PMID- 11292538
TI  - Elasticity of vesicles assessed by electron spin resonance, electron microscopy
      and extrusion measurements.
AB  - The composition of vesicles determines the physical state and elasticity of their
      bilayers. Fatty acid spin labels were incorporated into vesicles, composed of the
      single chain non-ionic surfactant octaoxyethylenelaurate-ester (PEG-8-L), the
      sucrose laurate-ester L-595 and cholesterol sulfate (CS) to monitor local dynamic
      properties of lipid molecules in vesicle bilayers and to study the elasticity of
      vesicle bilayers. Studies with the spin label probes 5-, 12- and 16-doxyl stearic
      acid (DSA) indicated that both the order parameter and the rotational correlation
      times increased when the doxyl group was positioned closer to the headgroup
      region. These findings indicate that the fluidity of membranes decreased near the
      headgroup region. Comparing 16-DSA incorporated in vesicle formulations with
      either 30 or 70 mol% showed no difference in alkyl chain mobility as was
      reflected by the order parameter. The rotational correlation times, however,
      showed a slowdown from 0.38 to 0.71 and 1.13 ns when the PEG-8-L molar content
      was decreased from 100 to 70 and 30 mol% for PEG-8-L:L-595:CS vesicles,
      respectively. Extrusion measurements indicated an increase in elasticity of
      vesicle bilayers as the molar content of PEG-8-L was increased from 10 to 90
      mol%. Incorporation of cholesterol sulfate stabilizes vesicles and thereby,
      decreases the elasticity. The increased elasticity correlated excellent with a
      reduction in the rotational correlation times observed. In conclusion, these
      results demonstrate that when the molar content of the single chain non-ionic
      surfactant PEG-8-L in vesicles is increased the elasticity is enhanced and the
      rotational correlation time is reduced. The enhanced elasticity might contribute
      to an optimal design of vesicles as drug carriers for transdermal application.

PMID- 11292539
TI  - Enhanced pulmonary delivery of insulin by lung lavage fluid and phospholipids.
AB  - Pulmonary delivery appears to be the most promising non-parenteral route of
      insulin administration. In this work, we investigated the enhancement of insulin
      absorption in the presence of phospholipids and lung lavage fluid in vivo and in
      vitro. In-vitro experiments of insulin uptake by type II cells showed a
      significantly enhanced absorption in presence of lavage fluid, compared to
      various buffer preparations. The same trend was obtained with in-vivo studies of
      tracheal instillation of insulin. The incorporation of phospholipids as
      absorption enhancers in 1,2-dipalmitoyl phosphatidylcholine (DPPC) dispersion was
      compared to blank liposomes. A significantly higher blood glucose decrease was
      observed with a DPPC-insulin physical mixture compared to liposome, suggesting a
      possible effect of the phospholipid chain physical state on the insulin in-vivo
      absorption.

PMID- 11292540
TI  - Drug release from and mechanical properties of press-coated tablets with
      hydroxypropylmethylcellulose acetate succinate and plasticizers in the outer
      shell.
AB  - Dissolution profiles of diltiazem hydrochloride (DIL) contained in core tablets
      from press-coated (PC) tablets with hydroxypropylmethylcellulose acetate
      succinate (HPMCAS) and plasticizers-adsorbent in the outer shell were
      investigated. Although, on the addition of triethyl citrate (TEC), triacetin
      (TA), and acetyltriethy citrate (ATEC) as plasticizers, DIL release was
      suppressed completely in first fluid (pH 1.2) for 10 h, it was not suppressed in
      HPMCAS on the addition of dibutyl sebacate (DBS) and acetylated monoglyceride. On
      the other hand, DIL in second fluid (pH 6.8) was released rapidly after a lag
      time in all the PC tablets. Water-soluble plasticizers such as TEC, TA, and ATEC
      showed greater compatibility to HPMCAS, and the results were consistent with
      suppression of DIL release in first fluid. Furthermore, as to PC tablets with
      HPMCAS and TEC-adsorbent, the DIL release in second fluid did not change after
      pretreatment in first fluid by the paddle-beads methods. To evaluate the
      resistance of the outer shell against such a mechanical impact, tablets with
      HPMCAS, HPMCAS and TEC- or DBS-adsorbent (H, HT, or HD tablets, respectively)
      were prepared. In compressive load-strain curves after immersion in first fluid,
      wet crushing strength was lower in the order of HT > H > HD tablets. Also, the
      curves of HT tablets at 3 and 21 h after immersion were quite different from
      those of other tablets, and it was hard to find crushing points. These results
      suggested that the resistance of the outer shell was due to plastic deformation
      properties involving some interaction between HPMCAS and TEC.

PMID- 11292541
TI  - The use of inverse phase gas chromatography to study the change of surface energy
      of amorphous lactose as a function of relative humidity and the processes of
      collapse and crystallisation.
AB  - The purpose of this study was to assess the effect of relative humidity (RH) on
      the surface energy of amorphous lactose. Two samples of amorphous lactose were
      investigated; a spray dried 100% amorphous material and a ball milled sample of
      crystalline lactose. The milled sample had less than 1% amorphous content by
      mass, but on investigation at 0% RH, yielded surface energies comparable to those
      obtained from the 100% amorphous material, indicating that the surface was
      amorphous. The effect of increasing humidity was to reduce the dispersive surface
      energy of the two samples from 36.0 +/- 0.14 and 41.6 +/- 1.4 mJ m(-2) at 0% RH
      for the spray dried and milled samples respectively, to a value comparable to
      that obtained for the crystalline alpha-lactose monohydrate of 31.3 +/- 0.41 mJ
      m(-2). The change in surface energy due to water sorption was only reversible up
      to 20% RH; after exposure to higher RH values subsequent drying did not result in
      a return to the original surface energy of the amorphous form. This shows that
      the surface is reorganising as the glass transition temperature (Tg) is reduced,
      even though the sample has not collapsed or crystallised. It was possible to
      follow the collapse behaviour in the column with ease, using a number of
      different methods.

PMID- 11292542
TI  - Gentamicin bone cements: characterisation and release (in vitro and in vivo
      assays).
AB  - Due to the extended use of acrylic bone cements, its necessary to develop
      improved formulations in order to resolve their many drawbacks. The present work
      was conducted to make a physical-chemical characterisation of this kind of
      acrylic cement in order to introduce future changes in the formulations to: (1)
      improve or at least maintain their mechanical properties; (2) diminish their
      toxicity, and (3) control the drug release (rate and amount). From the
      dissolution method we can conclude that the preparation method (with or without
      pressure) of specimens is not responsible for the erratic release. The cumulative
      amount of gentamicin released was fitted to a semi-empirical equation to explain
      the possible release mechanism. The powder size, shape and distribution that
      could affect several properties of bone cement were studied with the aid of
      different techniques such as SEM, laser diffraction spectroscopy, and powder X
      ray diffraction. From SEM micrographs, it was possible to observe that the
      surfaces of the specimens were very irregular with numerous small craters that
      may serve as conduits for eluting the antibiotic. An 'in vitro' drug diffusion
      model is proposed to elucidate the drug release mechanism. Finally an 'in vivo'
      study was performed to evaluate the antibiotic release to the neighbouring bone
      sites.

PMID- 11292543
TI  - A study of factors controlling dissolution kinetics of zinc complexed protein
      suspensions in various ionic species.
AB  - The presence of bound and unbound zinc in the crystal matrix of protein
      suspensions helps physically stabilize the crystal and limits the dissolution of
      the drug. In case of zinc insulin suspensions, dissolution can be promoted by
      complexation of zinc with an ionic species for which the zinc has a greater
      affinity, these complexing ions having either formulation and/or physiological
      relevance. The purpose of this work was to use ligand-complexed formulations of
      insulin suspensions to gain an understanding of these products' dissolution
      performance and to establish a fundamental understanding of the rate-limiting
      steps in zinc insulin dissolution. Our group has suggested that the critical
      factors to zinc insulin dissolution are: (1) chemical complexation (zinc with
      ionic species); and (2) drug transport (insulin diffusion and solubility).
      Dissolution studies conducted using different ionic species (acetate, phosphate,
      citrate and EDTA) in a spin-filter device demonstrated a rank order correlation
      for different sources of zinc insulin; it was observed that human zinc insulin
      dissolved faster than bovine insulin, these differences attributed to their
      binding properties and the respective affinities to the various ionic species
      used. Also, as the amount of crystallinity increased in a formulation, a rank
      order increase in dissolution times was observed. The project also identified a
      sensitive and reproducible dissolution testing methodology. Overall, this study
      demonstrated that: (1) the complexation rate-limiting step was more significant
      in the dissolution of zinc insulin than the diffusion rate-limiting step; and (2)
      that dissolution kinetics depended primarily on the source and solid state
      differences and the binding affinities of the zinc insulin.

PMID- 11292544
TI  - Influence of phloretin and 6-ketocholestanol on the permeation of progesterone
      through porcine skin.
AB  - In this study the effect of phloretin (PH) and 6-ketocholestanol (KC) on the
      permeation of progesterone through porcine skin has been examined. Both PH and KC
      were incorporated into unilamellar L-alpha-phosphatidylcholine (PC) liposomes at
      different concentrations (7.5, 15, 30 and 60 mol%). In diffusion experiments with
      porcine skin, both substances, to a different degree, enhanced the steady state
      flux of progesterone. It was increased up to 2.4-fold using 15 mol% KC, and 1.4
      fold using 30 mol% PH. The results indicate an interaction of these two compounds
      with the lipid components of the stratum corneum. In order to visualise the
      interaction, differential scanning calorimetry (DSC) measurements were performed
      on porcine skin, which had been impregnated with KC and PH. Both showed a
      lowering ( approximately 5-6 degrees C) in the lipid phase transition temperature
      that occurs around 75 degrees C in porcine skin.

PMID- 11292545
TI  - An investigation of mucus/polymer rheological synergism using synthesised and
      characterised poly(acrylic acid)s.
AB  - A range of poly(acrylic acid)s with different average degrees of polymerisation
      and cross-linking densities were synthesised using a solution polymerisation
      process. The rheological characteristics of aqueous dispersions of these
      materials and those of mixtures with homogenised pigs gastric mucus were
      investigated using dynamic oscillatory rheology, and compared to the known
      mucoadhesive Carbopol 934P. From the storage moduli, the rheological synergy and
      relative rheological synergy were calculated, and the effects of concentration
      and pH on this considered. Generally, the larger the molecular weight (and degree
      of cross-linking), the greater the rheological synergy, with Carbopol 934P giving
      the most pronounced effect. Rheological synergy was seen to be concentration
      dependent, and a maximum concentration to produce an optimum effect was evident.
      Acid pHs were seen to favour synergy, although in marked contrast to previous
      literature reports, the optimum mucus-polymer interaction was not observed at the
      half ionised value (pH = pKa) but at pH regimes that were unique to each polymer
      type. This could be influenced by the structural constrains imposed on potential
      hydrogen bonded interactions. It was concluded that synthesising poly(acrylic
      acid)s with better defined physicochemical properties than commercially available
      polymers will advance the study of the phenomenon of rheological synergy.

PMID- 11292546
TI  - Pharmacokinetics of a new antitumor 3-arylisoquinoline derivative, CWJ-a-5.
AB  - 1-(4-Methylpiperazinyl)-3-phenylisoquinoline hydrochloride (CWJ-a-5) is a newly
      developed from benzo[c]phenanthridine alkaloids and derivative and has exhibited
      potent antitumor activities, in vitro and in vivo. The pharmacokinetics of this
      novel antitumor 3-arylisoquinoline derivative was studied after intravenous
      (i.v.), oral (p.o.) and hepatoportal (p.v.) administration in rats. A simple high
      performance liquid chromatographic method was developed to determine the
      concentrations of CWJ-a-5 in plasma, bile and urine. Plasma concentration
      profiles of CWJ-a-5 were best fitted by the two-compartment model after i.v.
      administration and showed a linear pharmacokinetic behavior up to 20 mg/kg doses.
      The half-life of CWJ-a-5 in the post-distributive phase (t1/2beta), total-body
      plasma clearance (CLt), and volume of distribution at steady-state (Vdss) were
      86.9 min, 5.72 l/h per kilogram and 9.79 l/kg, respectively, after i.v.
      administration of 10 mg/kg. Biliary and urinary excretion of CWJ-a-5 was < 1%
      after i.v. injection of 10 mg/kg. The bioavailability of CWJ-a-5 after p.o. and
      p.v. administration (50 and 10 mg/kg, respectively) was 52.9 and 72.2%,
      respectively. Gastrointestinal bioavailability was calculated to be 73.3%. The
      apparent partition coefficient (log P) of CWJ-a-5 between n-octanol and water was
      2.64. Plasma protein binding of CWJ-a-5 measured by the ultrafiltration method
      was > 95%.

PMID- 11292547
TI  - The effect of absorption enhancers on the initial degradation kinetics of insulin
      by alpha-chymotrypsin.
AB  - The goal of this investigation was to establish a fast method to screen various
      insulin absorption enhancers by following their effect on the initial kinetics of
      insulin incubated with alpha-chymotrypsin at 37 degrees C. A simple, sensitive
      and reproducible reversed phase high performance liquid chromatography (HPLC)
      method has been developed to carry out this goal. Linear responses (r > 0.999)
      were observed over the range of 0.4-4 U/ml for insulin. There was no significant
      difference (P < 0.05) between inter- and intra-day studies for insulin. The mean
      relative standard deviations (RSD%) of the results of within-day precision and
      accuracy of insulin were 12%. The assay was sensitive to detect the existence of
      any metabolite due to the addition of any absorption enhancers, even if it was
      not seen with insulin alone. Three metabolites (A-C) were detected only when
      insulin was incubated with alpha-chymotrypsin at 37 degrees C. Metabolite D was
      observed when either glycocholic acid (0.5, 1%) or taurochenodeoxycholate (0.5,
      1%) was incubated with insulin in the absence of alpha-chymotrypsin at 37 degrees
      C. The compounds that significantly increased insulin T50% were glycyrrhizic acid
      (0.5%) > deoxycholic acid (1%) > deoxycholic acid (0.5%) > glycyrrhizic acid (1%)
      > cholic acid (0.5, 1%). Capric acid (0.5%), hydroxypropyl-alpha-cyclodextrin
      (0.5, 1%) and dimethyl-alpha-cyclodextrin (0.5, 1, 5%) did not significantly
      affect insulin T50%. The bile salts increased insulin T50% in this order:
      deoxycholate > cholate > glycocholate > taurocholate > taurodeoxycholate >
      taurochenodeoxycholate > glycodeoxycholate. The results obtained would support
      the feasibility of utilizing such method for screening any compound incorporated
      in insulin formulation. These compounds should be used in the minimum possible
      concentration to avoid or minimize insulin degradation.

PMID- 11292548
TI  - Intranasal bioavailability of buprenorphine in rabbit correlated to sheep and
      man.
AB  - The purpose of the present study of buprenorphine is to add information about the
      correlation between various animal models and nasal bioavailabilities in man. PEG
      300 was added to one formulation to study whether the addition of the co-solvent
      results in the same absorption pattern as seen for sheep. The bioavailability of
      intranasal buprenorphine 0.6 mg in PEG 300 and 5% dextrose was assessed in a
      cross-over study in six rabbits. The mean bioavailabilities, Tmax and Cmax were
      46% (S.D. +/-13) and 53% (S.D. +/-17), 8 and 12 min, 28 and 27 ng/ml for 30% PEG
      300 and 5% dextrose, respectively. No significant differences were found between
      the nasal buprenorphine formulations. The bioavailabilities in rabbit and sheep,
      respectively, were approximately 2.5 and four times higher than for man. The
      absorption rate was faster for rabbit and sheep than for man. It appears that
      rabbit and sheep bioavailability differ from humans, especially with respect to
      rate. PEG 300 do not increase the bioavailability of buprenorphine.

PMID- 11292549
TI  - Topical delivery of 5-fluorouracil (5-Fu) by 3-alkylcarbonyl-5-Fu prodrugs.
AB  - The solubilities in isopropyl myristate (SIPM) and pH 4.0 buffer (SAQ) and the
      partition coefficients between IPM and pH 4.0 buffer (KIPM:AQ) have been measured
      for a series of 3-alkylcarbonyl-5-fluorouracil prodrugs (3-AC-5-FU). The 3-AC-5
      FU prodrugs were all 100 times more soluble in IPM and the first two members of
      the series were also more soluble in pH 4.0 buffer than 5-FU. The abilities of
      the 3-AC-5-FU prodrugs to deliver total 5-FU species through hairless mouse skin
      from IPM suspensions (Ji) were also measured. The 3-propionyl derivative 3, which
      exhibited the highest SAQ in the series, gave the highest Ji value. The SIPM, SAQ
      and molecular weights (mw) of the 3-AC-5-FU series correctly predicted the rank
      order and very closely (0.10 log units) predicted the absolute values for logJi
      using the transformed Potts-Guy equation. Although the series of 3-AC-5-FU
      prodrugs was generally quite effective at increasing Ji (2-20 times), the best 3
      AC-5-FU prodrug was not as effective as the best 1-alkylcarbonyl-5-FU prodrug (1
      AC-5-FU) at increasing Ji and the ability of the 3-AC-5-FU prodrugs to increase
      the concentration of total 5-FU species in the skin was 2-5 times less than the 1
      AC-5-FU prodrugs. Thus, the 1-AC-5-FU prodrugs remain as the best prodrugs with
      which to enhance the topical delivery of 5-FU.

PMID- 11292550
TI  - Polymer particle erosion controlling drug release. I. Factors influencing drug
      release and characterization of the release mechanism.
AB  - The present study deals with controlled drug delivery from hydrocolloid tablets
      by polymer particle erosion. The influence of excipients and formulation factors
      on the dissolution behaviour of the methyl hydroxyethyl cellulose (MHEC)-tablets
      is investigated. Linear drug release with low susceptibility to hydrodynamic
      stress is obtained. The use of drugs with higher solubility leads to a slight
      acceleration of the release due to the contribution of diffusion to the release
      process. Higher drug loading and consequently lower polymer content expedites
      dissolution as well as changes in the tablets' geometry resulting in enlarged
      release surfaces. Furthermore, alterations of the composition of the dissolution
      medium affect drug release. However, neither viscosity grade nor the particle
      size of the polymer or compaction pressure has a marked impact on the
      dissolution. Investigations to clarify the mechanism of polymer particle erosion
      include erosion studies and the comparison of different batches of MHEC, of
      products from different manufacturers and of fibrous trial products. There is
      evidence that the insoluble fibres within the water soluble MHEC are responsible
      for the occurrence of polymer particle erosion by disturbing swelling and
      formation of a thick coherent gel layer and thus, causing erosion of the
      hydrocolloid tablet with synchronous drug release.

PMID- 11292551
TI  - HPLC evaluation of diclofenac in transdermal therapeutic preparations.
AB  - High-performance liquid chromatography (HPLC) was selected for analytical
      evaluation of sodium diclofenac in original transdermal therapeutic preparations
      containing adjuvant substances (capsaicin, hyoscyamine). After isolation from
      laminated adhesive patches, diclofenac was analysed on columns with reversed
      phase, using the mobile phase ethanol and phosphate buffer (pH 6.5) with an
      addition of tetrabutylammonium iodide and detection at 284 nm. Not only the total
      amount of diclofenac in the patch was evaluated, but HPLC methodology was also
      employed to select a suitable acceptor medium for permeation experiments. In
      patches manufactured in the tested series, HPLC was also employed to examine the
      release of diclofenac and its in vitro permeation through the human skin.

PMID- 11292552
TI  - Steam sterilisation of vesicular phospholipid gels.
AB  - Vesicular phospholipid gels (VPGs), highly concentrated phospholipid dispersions
      of semisolid consistency and vesicular morphology are under investigation as
      potential implantable depots for sustained release of drugs and as intermediates
      for subsequent dilution into 'conventional' liposome dispersions. It was
      investigated here if VPGs can be steam sterilised. VPGs prepared from 400 mg/g
      egg-phosphatidylcholine by high-pressure homogenisation retained their vesicular
      structure but showed a slight increase in vesicle size (freeze-fracture electron
      microscopy). However, autoclaving slowed down both, the in vitro release of the
      hydrophilic marker carboxyfluorescein and vesicles from VPGs. This was assumed to
      be due to bigger vesicle sizes and corresponding increase in packing density of
      the vesicular matrix. Upon dilution into a liposome dispersion both negative
      staining electron microscopy and dynamic laser light scattering analysis
      confirmed a distinct increase in liposome size, mainly due to fusion of small (20
      nm) vesicles with unfavourable curvature. This was consistent with the observed
      increase in encapsulation efficiency of carboxyfluorescein. Phospholipid
      hydrolysis during autoclaving was negligible with lysophosphatidylcholine
      formation of less than 2% (thin layer chromatography). Despite significant change
      of their morphological and functional properties during autoclaving VPGs retained
      their main characteristics, such as vesicular structure, sustained release and
      dilutability to liposome dispersions, and are, therefore, considered as
      autoclavable.

PMID- 11292553
TI  - Quantitative determination of the specific heat and the glass transition of moist
      samples by temperature modulated differential scanning calorimetry.
AB  - In differential scanning calorimetry (DSC), remnant moisture loss in samples
      often overlaps and distorts other thermal events, e.g. glass transitions. To
      separate such overlapping processes, temperature modulated DSC (TMDSC) has been
      widely used. In this contribution we discuss the quantitative determination of
      the heat capacity of a moist sample from TMDSC measurements. The sample was a
      spray-dried pharmaceutical compound run in different pans (hermetically-sealed
      pan, pierced lid pan [50 microm] and open pan). The apparent heat capacity was
      corrected for the remaining amount of moisture. Using this procedure we could
      clearly identify the glass transition of the dry and the moist sample. We found
      that a moisture content of about 6.2% shifts the glass transition by about 50
      degrees C.

PMID- 11292554
TI  - Clearance characteristics of chitosan based formulations in the sheep nasal
      cavity.
AB  - This paper describes the clearance characteristics of two bioadhesive nasal
      delivery systems in the form of chitosan microspheres and chitosan solution, from
      the nasal cavity of conscious sheep. The pattern of deposition and clearance of
      the nasal dosage forms were evaluated using a radioactive tracer and the non
      invasive technique of gamma scintigraphy. The clearance of chitosan microsphere
      and solution formulations was compared with that of a control solution. The data
      show that the control was cleared rapidly from the sheep nasal cavity with a half
      time of clearance (time taken for 50% clearance; t(50%)) of about 15 min. The
      bioadhesive chitosan delivery systems were cleared at a slower rate, with half
      times of clearance of 43 min and 115 min, for solution and microsphere
      formulations respectively. From the results reported in this study it can be
      concluded that the chitosan delivery systems investigated had significantly
      reduced rates of clearance from the sheep nasal cavity, as compared to the
      control. Consequently, chitosan delivery systems have the ability to increase the
      residence time of drug formulations in the nasal cavity thereby providing the
      potential for improved systemic medication. The nasal clearance rates recorded in
      the sheep model mimic very closely the clearance rates found in a previous study
      using human subjects. It can also be concluded that the sheep can be considered a
      suitable model for in vivo nasal clearance studies of novel bioadhesive drug
      delivery systems.

PMID- 11292555
TI  - Correlation of in vitro and in vivo acetaminophen availability from albumin
      microaggregates oral modified release formulations.
AB  - The aim of this study was to develop albumin microaggregated oral formulations
      for controlled drug release, and to reveal the possible influence of the release
      site on drug absorption. Acetaminophen was chosen as the model drug, which is
      included in the Class 1 group of the Biopharmaceutics Classification System
      (BCS). Albumin micro aggregates were formulated into tablets to obtain different
      drug release rates: Immediate Release (IR) tablets, multiparticulate systems with
      an intermediate release rate, and matrix systems showing slow release rate. The
      properties of the products were initially tested via dissolution studies, and
      then via bioavailability studies in healthy volunteers. Controlled release
      albumin microaggregated acetaminophen formulations for oral administration were
      obtained. The extent of drug absorption was comparable for all formulations,
      suggesting that the differences found in saliva concentration and urine
      cumulative profiles could be attributed merely to differences in drug release
      kinetics, as confirmed by the in vitro-in vivo correlation study. Therefore, it
      can be concluded that extended release of acetaminophen does not influence its
      absorption via intestinal heterogeneity.

PMID- 11292556
TI  - One-dimensional filtration of pharmaceutical grade phyllosilicate dispersions.
AB  - The filtration behaviour of some clay-water dispersions was studied. Two Spanish
      fibrous phyllosilicates (sepiolite from Vicalvaro and palygorskite from Turon)
      and a commercial bentonite (Bentopharm UK) with similar sizes and different
      morphologies (fibrous and/or laminar) were selected as model clays. Sepiolite
      from Vicalvaro is an almost pure fibrous sample, Bentopharm presents a high
      amount of laminar particles and palygorskite from Turon is made up of similar
      percentages of laminar and fibrous particles. The disperse systems were made up
      using a rotor-stator mixer working at two different mixing rates (1000 and 8000
      rpm), for periods of 1 and 10 min. Filtration measurements were taken and the
      corresponding filtration curves obtained. Finally, the desorptivity (S) of the
      filtration cakes was calculated and correlated to the textural characteristics of
      the materials, the solid fraction and mixing conditions. Filtration behaviour of
      the dispersions depended on all three of these factors. Laminar dispersions
      presented lower S values than fibrous dispersions. In the 2% w/v dispersions the
      bridging forces between particles did not permit formation of an interconnected
      network as in 10% w/v dispersions and, consequently, filtration times increased
      with the solid fraction (i.e. S values decreased). Regarding stability to pH
      changes, the results showed that filtration behaviour was highly sensitive to
      basic pH in the fibrous clay dispersions and almost insensitive in the laminar
      clay dispersions.

PMID- 11292557
TI  - The effect of polysialylation on the immunogenicity and antigenicity of
      asparaginase: implication in its pharmacokinetics.
AB  - Erwinia carotovora L-asparaginase was conjugated via the epsilon-amino groups of
      its lysine residues with colominic acid (CA) (polysialic acid) of average
      molecular mass of 10 kDa by reductive amination in the presence of NaCNBH3.
      Polysialylation using 50-, 100- and 250-fold molar excess CA relative to the
      enzyme led to an increasing proportion of the enzyme's in-amino groups (5.8, 7.6
      and 11.3%, respectively) being conjugated to CA. Polysialylated and native
      (intact) asparaginase were used to immunize mice intravenously. Results (total
      IgG immune responses) indicate that all preparations elicited antibody production
      against the enzyme moiety but not against the CA of the conjugates. Moreover,
      antibody titres appeared highest for the native enzyme and were generally reduced
      as the degree of polysialylation increased. In other experiments mice pre
      immunized with native or polysialylated asparaginase, with anti-asparaginase
      antibodies in their blood, were injected intravenously with the corresponding
      enzyme preparations. Results revealed that polysialylation reduces the
      antigenicity of asparaginase thus leading to circulatory half-lives (t 1/2 beta)
      that were 3-4-fold greater than that of the native enzyme, and similar to those
      observed in naive, non-immunized mice. Our data suggest that polysialylation of
      therapeutic enzymes and other proteins may be useful in maintaining their
      pharmacokinetics in individuals with antibodies to the therapeutic proteins as a
      result of chronic treatment.

PMID- 11292558
TI  - Dynamic solid-state and tableting properties of four theophylline forms.
AB  - Relationships between solid-state, densification and compact properties of
      theophylline monohydrate (TMO), a mixture of forms (TMIX), and anhydrous
      polymorphs I (TA-I) and II (TA-II) were evaluated. Solid-state identification of
      powders and compacts was accomplished by powder X-ray diffraction. A compaction
      simulator was used to assess deformation behaviour of the powders and to prepare
      compacts. Porosity and tensile strength of the compacts were determined after
      1,24, and 168 h of storage at 22% relative humidity. TA-II was stable, whereas TA
      I, TMIX and TMO partially transformed to the TA-II form during storage. All
      theophylline modifications primarily deformed by plastic flow. Increased water
      content decreased resistance towards densification and deformation of TMIX and
      TMO when compared to TA-II or TA-I, demonstrating viscoelasticity. Permanent
      densification behaviours of TMIX and TMO approached to that of TA-II during
      storage. Tensile strength of the different theophylline forms were practically
      equal after 1 h of storage. Tensile strength and porosity of TMIX and TMO
      compacts increased during the storage. Dynamic solid-state transformations from
      TMO, TMIX and TA-I to TA-II were associated with parallel changes in their
      densification and compact properties. The extent of these changes was also
      dependent on the materials' water content.

PMID- 11292559
TI  - The influence of type and quantity of model drug on the extrusion/spheronization
      of mixtures with microcrystalline cellulose. I. Extrusion parameters.
AB  - Five model drugs, (methyl, propyl and butyl paraben, 4-hydroxybenzoic acid and
      propyl gallate), similar in their chemical structure were mixed with
      microcrystalline cellulose and water in different proportions and forced through
      a ram extruder. The overall water movement was measured by the difference between
      the initial water in the formulation and the water content in the plug remaining
      after extrusion was completed. The differences in theoretical and practical
      volume occupancy of the materials inside the barrel were calculated to look for
      trapped air inside the barrel. The steady-state extrusion force for each
      formulation was recorded. All five materials demonstrated differences in
      behaviour during extrusion. The relationship between each of the three properties
      measured and both the drug-load and initial water content was examined, to
      establish the potential relationship that existed between the differences due to
      the drug models. The five drug models were divided into two sub-groups, when
      examining the way that they underwent extrusion. Methyl, propyl and butyl paraben
      formed one group while 4-hydroxybenzoic acid and propyl gallate formed the other
      group. Within the former group the relationship between steady-state extrusion
      force and the percentage of drug and water present tended to be lower than those
      in the latter group. For the former group these relationships were non-linear.

PMID- 11292560
TI  - Electroporation of the skin to deliver antigen by using a piezo ceramic gas
      igniter.
AB  - The static electricity generated by triggering a piezo gas igniter is shown to
      cause electroporation of the skin to deliver antigen. Mice were immunized with
      chicken albumin by electroporation using a piezo gas igniter and in another
      experiment, the gas igniter was replaced by a power supply. In both the groups
      identical immune responses were generated. The change in impedance of the skin of
      a mice after applying high voltage electrical pulses from a power supply and that
      with a gas igniter were found to be similar. The piezo gas igniter is an
      inexpensive and easily available device. It is much more user 'friendly' than a
      power supply used for electroporation and it may be viewed as a replacement for a
      syringe with a needle.

PMID- 11292562
TI  - Development of novel biomedicine based on genome science.
AB  - Towards the post genomic sequencing era, conventional drug discovery is
      drastically improving genomic technologies and computational advances. The
      completion of the entire genome sequence of many experimental organisms as well
      as the human organism allow us to compare several genomic sequences, comparative
      genomics, to get valuable information for gene discovery and functional genomics.
      Pharmacogenomic studies and chemical genomic investigations are quickly becoming
      fundamental techniques for genomic drug discovery. Additionally, progress in
      microchip and microarray technology has been stimulating genomic drug discovery
      studies. This paper reviews recent progress in human genome research, basic
      elements in the new strategy for drug discovery based on genome science, and
      future perspectives for the bio and pharmaceutical industries.

PMID- 11292563
TI  - Nucleotide synthesis via methods without nucleoside-base protection.
AB  - Oligonucleotide synthesis via methods without nucleobase protection (N
      unprotected methods) is briefly reviewed. The N-unprotected methods are
      advantageous in the following respects over conventional approaches that use
      protectors, generally, acyl protectors for the nucleobase (N-protected method).
      Two steps, introduction and removal of the protecting groups, are eliminated, and
      consequently use of undesirable reagents involved in these steps are avoided. In
      the synthesis of DNA oligomers, the risk of depurination of deoxyadenosine and
      deoxyguanosine derivatives, which is a serious problem in the N-protected
      methods, is considerably reduced. The range of synthesizable artificial analogues
      bearing base-labile functions is extended because harsh base treatment for the
      deprotection is eliminated.

PMID- 11292564
TI  - Nuclear targeting of DNA.
AB  - The nuclear membrane is a tight barrier for cytoplasmic proteins, but nuclear
      proteins have the intrinsic ability to overcome this barrier by an active signal
      mediated process. Specific cytoplasmic carrier proteins have the responsibility
      to escort these proteins into the nucleus through the nuclear pore. The nuclear
      membrane is also a tight barrier for exogenous DNA delivered by synthetic
      vehicles, while many of the karyophilic viruses have a mechanism to actively
      deliver their genome through the nuclear pore. Virus DNA and RNA cannot move into
      the nucleus by themselves and require the viral structural proteins for efficient
      nuclear transport. In this article, we review the recent progress in
      understanding the mechanism of the nuclear transport of proteins and the virus
      genome, and discuss the possibility of developing synthetic gene-delivery systems
      based on these outcomes.

PMID- 11292565
TI  - Photodynamic antisense regulation of human cervical carcinoma cell growth using
      psoralen-conjugated oligo(nucleoside phosphorothioate).
AB  - The antisense strategy has been applied to regulate gene expression in a sequence
      specific manner, which enables suppression of the proliferation of cancer cells
      and exploration of the functions of unknown genes. In order to generalize and to
      enhance the ability of the strategy, functionalization of antisense DNAs was done
      using a photo-crosslinking reagent, 4,5',8-trimethylpsoralen, and the possibility
      of photodynamic antisense regulation of gene expression was examined. Psoralen
      conjugated oligo(nucleoside phosphorothioate)s (Ps-S-oligo) were prepared and
      used to inhibit the proliferation of human cervical carcinoma cells. Upon UVA
      irradiation of Ps-S-oligo treated cells, Ps-S-oligo complementary to the
      initiation codon region (Ps-P-As) of HPV18-E6*-mRNA of human cervical carcinoma
      cells inhibited drastically the cell growth (IC(50)=16 nM). In contrast, Ps-S
      oligo with mismatched sequences and scrambled one showed lesser inhibitory
      effects than Ps-P-As. These results showed that the inhibition by Ps-S-oligo was
      dependent on (a) sequence, (b) UVA irradiation, (c) concentration and (d) cell
      line. The amount of intact HPV18-E6*-mRNA was decreased in a sequence dependent
      manner, indicating that the antiproliferative effect of Ps-P-As was an antisense
      manner. The psoralen-conjugated antisense DNA has significant potential to
      regulate gene expression, which may provide useful information to explore the
      novel gene regulating reagents.

PMID- 11292566
TI  - Physicochemical properties and nuclease resistance of antisense
      oligodeoxynucleotides entrapped in the core of polyion complex micelles composed
      of poly(ethylene glycol)-poly(L-lysine) block copolymers.
AB  - In this study, the physicochemical properties of polyion complex (PIC) micelles
      formed from antisense-oligodeoxynucleotides (antisense-ODN) and poly(ethylene
      glycol)-poly(L-lysine) block copolymers (PEG-PLL) were investigated to utilize
      them as a novel formulation for antisense-ODN delivery. Angular and concentration
      dependences of the diffusion coefficient of PIC micelles were evaluated by
      dynamic light scattering. Results suggested that the formed PIC micelles may have
      spherical shape with core-shell structure, in which the PIC core formed from
      antisense-ODN and PLL segment was surrounded by a PEG shell. The average radius
      of PIC micelles was dependent on the chain length of the PLL segment and was not
      influenced by the change in the length of ODN molecules at least in the range
      between 15 and 20 base pairs. Critical association concentration (cac) of PIC
      micelles was then determined from a profile of light scattering intensity versus
      concentration (Debye plots). Cac is ca. 0.20 mg/ml, which is low enough to ensure
      the micelle stability in very diluted condition as is the case with systemic
      injection into the blood compartment for antisense-ODN therapy. Furthermore, the
      stability of antisense-ODN against deoxyribonuclease I (DNase I) attack was
      evaluated using capillary gel electrophoresis, revealing that the complexation of
      antisense-ODN with PEG-PLL effectively prohibited DNase I attack. These
      characteristics of the PIC micelle system highlight its promising feature as ODN
      carrier used in the field of targeting therapy.

PMID- 11292567
TI  - Active oligonucleotides incorporating alkylating an agent as potential sequence-
      and base selective modifier of gene expression.
AB  - A number of cross-linking (alkylating) agents have been developed and
      incorporated into the oligonulceotides for sequence selective control of gene
      expression. Recently, potential application of such active oligonucleotides has
      been expanding from use for improvement of inhibition efficiency to new
      biotechnology that may enable chemical alteration of genetic information. These
      interests in active oligonucleotides have encouraged the generation of new cross
      linking agents that exhibit high efficiency for application of either in vitro or
      in vivo. This mini review summarizes structures of alkylating agents, in
      particular, a new basic skeleton for cross-linking, a 2'-deoxyribose derivative
      of 2-amino-6-vinylpurine that has been recently developed by the author's group.
      The 2-amino-6-vinylpurine has been shown to form a complex with cytidine under
      acidic conditions, and brings the vinyl and the amino reactive groups into
      proximity to achieve efficient alkylation. A new strategy was designed so that
      the reactivity of 2-amino-6-vinylpurine can be induced from the corresponding
      phenylsulfoxide derivative within a duplex with the complementary strand. The
      validity of the new strategy has been proven by achievement of cytidine-selective
      cross-linking with remarkably efficiency.

PMID- 11292568
TI  - Tetracycline-regulatable adenovirus vectors: pharmacologic properties and
      clinical potential.
AB  - Stringent control of gene expression in human gene therapy strategies is
      important for both therapeutic and safety reasons. Replication-defective vectors
      derived from adenoviruses have been shown to be capable of highly efficient in
      vivo gene delivery to a wide variety of dividing and nondividing human cells.
      Here, we review the progress in the development of regulatable adenovirus vectors
      that allow gene expression to be tightly controlled by low concentrations of
      tetracyclines. As an example of the potential clinical utility of this
      technology, we highlight our results obtained in an immunotherapy model for
      prostate cancer with a tetracycline-regulatable adenovirus vector expressing the
      cytokine interleukin-12. Recombinant adenovirus vectors with tetracycline
      regulatable gene expression provide new opportunities and improved safety for
      gene therapy applications in humans.

PMID- 11292569
TI  - Antisense therapy of influenza.
AB  - The liposomally encapsulated and the free antisense phosphorothioate
      oligonucleotides (S-ODNs) with four target sites (PB1, PB2, PA, and NP) were
      tested for their abilities to inhibit virus-induced cytopathogenic effects by a
      MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to
      the sites of the PB2-AUG initiation codon showed highly inhibitory effects. On
      the other hand, the inhibitory effect of the liposomally encapsulated S-ODN
      targeted to PB1 was considerably decreased in comparison with those directed to
      the PB2 target sites. The liposomally encapsulated antisense phosphorothioate
      oligonucleotides exhibited higher inhibitory activities than the free
      oligonucleotides, and showed sequence-specific inhibition, whereas the free
      antisense phosphorothioate oligonucleotides were observed to inhibit viral
      absorption to MDCK cells. Therefore, the antiviral effects of S-ODN-PB2-AUG and
      PA-AUG were examined in a mouse model of influenza virus A infection. Balb/c mice
      exposed to the influenza virus A (A/PR/8/34) strain at dose of 100 LD(50)s were
      treated i.v. with various doses (5-40 mg/kg) of liposomally (Tfx-10) encapsulated
      PB2-AUG or PA-AUG before virus infection and 1 and 3 days postinfection. PB2-AUG
      oligomer treated i.v. significantly prolonged the mean survival time in days
      (MDS) and increased the survival rates with a dose-dependent manner. We
      demonstrate the first successful in vivo antiviral activity of antisense
      administered i.v. in experimental respiratory tract infections induced with
      influenza virus A.

PMID- 11292570
TI  - Development of gene drug delivery systems based on pharmacokinetic studies.
AB  - A series of pharmacokinetic studies following systemic or local administration
      for the development of delivery systems for gene drugs, such as plasmid DNA and
      oligonucleotides, are reviewed. The pharmacokinetics of gene drugs after
      intravenous injection into mice was evaluated based on clearance concepts.
      Pharmacokinetic analysis revealed that the overall disposition characteristics of
      the gene drug itself were determined by the physicochemical properties of its
      polyanionic DNA. Based on these findings, liver cell-specific carrier systems via
      receptor-mediated endocytosis were successfully developed by optimizing
      physicochemical characteristics. On the other hand, the pharmacokinetics of gene
      drugs after intratumoral injection were assessed in a tissue-isolated tumor
      perfusion system. The relationship between the physicochemical properties of gene
      drug delivery systems and intratumoral pharmacokinetics was determined and the
      therapeutic effect was also discussed in relation to pharmacokinetics.
      Collectively, it was demonstrated that a rational design of gene drug delivery
      systems that can control their in vivo disposition is possible by means of
      pharmacokinetic studies at whole body, organ and cellular levels.

PMID- 11292571
TI  - An approach to metal-assisted DNA base pairing: novel beta-C-nucleosides with a 2
      aminophenol or a catechol as the nucleobase.
AB  - The metal-chelating beta-C-nucleoside having a phenylenediamine moiety as the
      nucleobase was previously found to form a stable 2:1 complex with a Pd(2+) ion in
      aqueous media, where hydrogen bonding is replaced by metal coordination in the
      base pairing, thereby creating a novel hybridization motif in duplex DNA. In this
      regard, we have further designed two types of artificial beta-C-nucleosides
      possessing a metal-chelating site (a 2-aminophenol or a catechol) as the
      nucleobase moiety. These artificial nucleosides are directed toward controlling
      the net charges of the metal-assisted base pairs. This paper describes convenient
      syntheses of the artificial nucleosides bearing a 2-aminophenol or a catechol
      moiety. Each nucleoside was directly synthesized through 2'-deoxy derivative via
      a Friedel-Crafts coupling reaction as the key step between the aromatic ring and
      ribose moiety, whereas the nucleoside having a phenylenediamine moiety was
      prepared in rather longer steps through an RNA type intermediate followed by the
      removal of 2'-hydroxyl group.

PMID- 11292572
TI  - Intracellular control of gene trafficking using liposomes as drug carriers.
AB  - The objective of this review is to summarize some of the critical barriers in
      gene delivery and recent progress in overcoming such barriers using non-viral
      carrier systems. Receptor-mediated endocytosis is generally considered to be a
      principal entering pathway. Therefore, endosomal escape is an essential step for
      achieving efficient transfection. The nuclear membrane is also a critical barrier
      in gene delivery and the application of the nuclear localization signal is
      discussed, based on recent strategies. It is essential to optimize the carrier
      system, in order to enhance the transfection ability equivalent to a viral
      system. The importance of developing an intracellular pharmacokinetic model of
      genes is emphasized in the optimization of non-viral carrier systems.

PMID- 11292573
TI  - Design of novel zinc finger proteins: towards artificial control of specific gene
      expression.
AB  - In this review, we summarize design strategies for generating proteins with
      desired sequences such as long contiguous base pairs and diverse sequence
      specificities based on the nature of Cys(2)-His(2) zinc finger proteins. Recent
      progress towards artificial DNA binding proteins has been achieved by structure
      based design processes and by selection strategies. Indeed, a multi-zinc finger
      protein with an 18 (or 27)-base pair address, and new zinc finger proteins for
      diverse DNA target sites (TATA-box and p53 binding site) have been created
      successfully. Such novel zinc finger proteins will probably be useful tools in
      molecular biology and potentially in human medicine.

PMID- 11292574
TI  - Enhanced throughput for DNA sequencing by capillary array electrophoresis with a
      gradient of electric field strength.
AB  - The effect of electric field gradients are examined on the speed, selectivity,
      read length, and accuracy for DNA sequencing using capillary array
      electrophoresis. Modified electric field gradients was realized to read over 800
      bases within 140 min. The method developed is effectively applicable to single
      nucleotide polymorphism analysis for genomic drug discovery and pharmacogenomics.

PMID- 11292575
TI  - Covalent glutathione conjugation to cyanobacterial hepatotoxin microcystin LR by
      F344 rat cytosolic and microsomal glutathione S-transferases.
AB  - Most investigators report that microcystins (MCs) bound covalently to SH
      compounds, such as L-cysteine and reduced glutathione (GSH). However, their
      studies were based on a high pH condition. In the present study, we investigated
      the reaction between microcystin LR (MCLR) and GSH in various pH conditions. As a
      result, we found that no MCLR conjugated with GSH in these conditions, and MCLR
      mixed with GSH showed different peaks of retention time compared with intact MCLR
      on the high performance liquid chromatography-mass spectrometry (LC-MS)
      chromatograms. Furthermore, we found the GSH conjugate of MCLR was detected in
      the glutathione S-transferase (GST) assay using F344 rat liver cytosol and
      microsomes. This indicates that the covalent GSH conjugation was caused only by
      an enzymatic activity. We conclude, therefore, that the reaction is caused by
      enzymatic action and is not due to the Michael reaction.

PMID- 11292576
TI  - Calcium preventing locomotor behavioral and dental toxicities of fluoride by
      decreasing serum fluoride level in rats.
AB  - Spontaneous motor activity, rota-rod performance (motor co-ordination), body
      weight gain, food intake, activities of total cholinesterase (blood) and
      acetylcholinesterase (brain), and dental structure were determined in adult
      female rats treated with a very high dose of sodium fluoride (500 ppm in drinking
      water) alone and in combination with calcium carbonate (50 mg/kg body weight by
      oral intubation) for 60 days. The concentration of fluoride and calcium were
      measured in the serum of these animals. Administration of sodium fluoride with
      drinking water produced both behavioural and dental toxicities and not lethality
      in the present study. A suppression of spontaneous motor activity, a shortening
      of rota-rod endurance time, a decreased body weight gain and food intake, a
      suppression of total cholinesterase and acetylcholinesterase activities and
      dental lesion were observed in test animals. Serum fluoride concentration was
      raised markedly and that of calcium was decreased in these animals. The effects
      of sodium fluoride were prevented significantly when animals received calcium
      carbonate along with sodium fluoride. Serum fluoride content was decreased and
      that of calcium was restored to control level in these animals. These results
      indicate that calcium prevents not only fluoride-induced hypocalcemia but also
      the locomotor behavioral and dental toxicities of fluoride by decreasing
      bioavailability of fluoride.

PMID- 11292577
TI  - Nuclear factor-kappaB activation is higher in peripheral blood mononuclear cells
      of male smokers.
AB  - Nuclear factor-kappaB (NF-kappaB) is an oxidative stress sensitive transcription
      factor involved in the regulation of inflammatory genes. Activation of NF-kappaB
      results into increased expression of inflammatory genes such as for interleukins,
      endothelial cell leukocyte adhesion molecules and inducible NO synthase. Our
      study, with six smokers and 10 non-smokers, showed that NF-kappaB activity in
      peripheral blood mononuclear cells of smokers compared to non-smokers is
      significantly higher (P<0.05). This indicates that NF-kappaB is involved in
      cigarette smoke induced inflammatory responses and that NF-kappaB activation can
      be used as a functional marker of oxidative stress.

PMID- 11292578
TI  - Quantitative exposure assessment: application of physiologically-based
      pharmacokinetic (PBPK) modeling of low-dose, long-term exposures of organic acid
      toxicant in the brain.
AB  - Our objective was to construct a physiologically-based pharmacokinetic (PBPK)
      model describing the kinetic behavior of 2,4-dichlorophenoxyacetic acid (2,4-D)
      on rats after long-term exposures to low doses. Our study demonstrated the
      model's ability to simulate uptake of 2,4-D in discrete areas of the rat brain.
      The model was derived from the generic PBPK model that was first developed for
      high-dose, single exposures of 2,4-D to rats or rabbits (Kim, C.S., Gargas, M.L.,
      Andersen, M.E., 1994. Pharmacokinetic modeling of 2,4-dichlorophenoxyacetic acid
      (2,4-D) in rats and rabbits brain following single dose administration. Toxicol.
      Lett. 74, 189-201; Kim, C.S., Slikker, W., Jr., Binienda, Z., Gargas, M.L.,
      Andersen, M.E., 1995. Development of a physiologically based pharmacokinetic
      (PBPK) model for 2,4-dichlorophenoxyacetic acid (2,4-D) dosimetry in discrete
      areas of the brain following a single intraperitoneal or intravenous dose.
      Neurotox. Teratol. 17, 111-120.), to which a subcutaneous (hypodermal)
      compartment was incorporated for low-dose, long-term infusion. It consisted of
      two body compartments, along with compartments for venous and arterial blood,
      cerebrospinal fluid, brain plasma and six brain regions. Uptake of the toxin was
      membrane-limited by the blood-brain barrier with clearance from the brain
      provided by cerebrospinal fluid 'sink' mechanisms. This model predicted profiles
      of 2,4-D levels in brain and blood over a 28-day period that compared well with
      concentrations measured in vivo with rats that had been given 2,4-D (1 or 10
      mg/kg per day) with [14C]-2,4-D subcutaneously (s.c.) for 7, 14, or 28 days,
      respectively. This PBPK model should be an effective tool for evaluating the
      target tissue doses that may produce the neurotoxicity of organic acid toxicants
      after low-dose, long-term exposures to contaminated foods or the environment.

PMID- 11292579
TI  - Effects of the antioxidants dihydrolipoic acid (DHLA) and probucol on xenobiotic
      mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes
      in vitro(1).
AB  - The antioxidant effects of dihydrolipoic acid (DHLA) and probucol were
      investigated in a human erythrocytic in-vitro model of diabetic oxidative stress,
      where xenobiotics were used to form methaemoglobin. 4-Aminophenol mediated
      haemoglobin oxidation in non-diabetic erythrocytes was not affected by the
      presence of either DHLA or probucol. However, with diabetic cells, there were
      significant increases (P<0.01) in 4-aminophenol-mediated haemoglobin oxidation in
      the presence of DHLA. Methaemoglobin formed by nitrite in non-diabetic and
      diabetic cells was not altered by either DHLA or probucol except at one time
      point in diabetic cells. In non-diabetic as well as diabetic cells,
      methaemoglobin formed by MADDS-NHOH was significantly reduced at all three time
      points in the presence of DHLA (P<0.0001) but unaffected by probucol. In the
      presence of DHLA only, methaemoglobin formed by the products of rat microsomal
      oxidation of both 4-aminopropiophenone and benzocaine was markedly reduced for
      both xenobiotics in diabetic and non-diabetic cells (P<0.0001) compared with
      cells incubated in the absence of DHLA. There were no significant differences
      between total cellular thiol levels determined between diabetic and non-diabetic
      erythrocytes, nor did DHLA or probucol affect resting thiol levels. MADDS-NHOH
      caused a significant thiol depletion in diabetic cells, which was restored in the
      presence of DHLA. A further study is required to determine how DHLA attenuates
      the potent REDOX reactions that occur during hydroxylamine-mediated
      methaemoglobin formation.

PMID- 11292580
TI  - Elevation of serum 17-beta-estradiol in channel catfish following injection of 17
      beta-estradiol, ethynyl estradiol, estrone, estriol and estradiol-17-beta
      glucuronide.
AB  - 17-beta-Estradiol is naturally converted in numerous organisms to various
      derivatives/metabolites, which may be excreted from the organism into its
      immediate external environment. There is a paucity of data regarding the
      biological effects of these derivatives/metabolites on aquatic organisms. Male
      channel catfish (200-500 g, N=5, 12-18 months) were injected with 1 mg/kg 17-beta
      estradiol (E2), ethynyl estradiol (EE2), estrone, estriol or E2-17-beta
      glucuronide with subsequent measurements of vitellogenin (Vtg) and serum E2
      concentrations 7 days post injection. EE2 and E2 gave the largest magnitude of
      Vtg response followed by estrone and estriol. Exposure to EE2, estrone, and E2-17
      beta-glucuronide all induced significant increases in serum E2 concentrations.
      This study indicates that metabolites of E2 are also estrogenic and may
      potentially disrupt estrogen feedback loops within aquatic organisms.

PMID- 11292581
TI  - Combined administration of a chelating agent and an antioxidant in the prevention
      and treatment of acute lead intoxication in rats.
AB  - The administration of chelating agents, meso 2,3-dimercaptosuccinic acid (DMSA),
      monoisoamyl DMSA (MiADMSA) either individually or in combination with an
      antioxidant, n-acetylcysteine (NAC) in the prevention and treatment of acute lead
      intoxication in rats, was investigated. The results suggest that concomitant oral
      supplementation of DMSA with lead was most effective in preventing the inhibition
      of lead sensitive blood delta-aminolevulinic acid dehydratase (ALAD) activity in
      blood, elevation of zinc protoporphyrin level and the alterations in hepatic
      reduced and oxidized glutathione (GSH and GSSG) contents. A number of other
      biochemical variables either remained insensitive to lead exposure or responded
      moderately to chelation treatment. Combined administrations of NAC plus DMSA was
      most effective when given during lead exposure or post exposure, followed by DMSA
      and MiADMSA alone or NAC plus MiADMSA treatment, in reducing the accumulation of
      lead in blood and liver. Administration of NAC alone was only mildly effective in
      preventing lead absorption in the blood and tissues. The results suggest that
      combined administration of DMSA and NAC could be a more effective treatment
      protocol for acute lead toxicity, keeping in view its beneficial effect on
      oxidative injury.

PMID- 11292583
TI  - Erratum to "Comparative characterization of CHCl(3) metabolism and toxicokinetics
      in rodent strains differently susceptible to chloroform-induced carcinogenicity"

PMID- 11292582
TI  - Effects of developmental lead exposure on inhibitory avoidance learning and
      glutamate receptors in rats.
AB  - Chronic lead (Pb) exposure during development is known to produce learning
      deficits. AMPA and NMDA receptors have been shown to participate in the synaptic
      mechanisms involved in certain forms of learning and memory. We investigated
      whether the effects of Pb on AMPA and NMDA receptors are associated with Pb
      induced impairment in learning and memory. Rats were exposed to 0.2% lead acetate
      at different developmental stages including a maternally exposed group (including
      gestation and lactation period), a postweaning exposed group, and a continuously
      exposed group. Lead treatment impaired learning acquisition, but not memory
      retention in step-down avoidance learning task in all treatment groups. In
      parallel with the behavioral data, autoradiographic analyses of brain sections
      indicated that the [3H]AMPA binding was decreased in the CA1 and dentate gyrus of
      the hippocampus and entorhinal cortex in all three Pb-exposed groups. However, an
      increase in [3H]MK801 binding was only observed in CA1 of the hippocampus in the
      continuously Pb-exposed rats. The findings suggest that alterations in AMPA
      receptor may contribute to the Pb-induced deficits in learning acquisition of
      inhibitory avoidance.

PMID- 11292584
TI  - Microbes and microbial Toxins: paradigms for microbial-mucosal toxins. V.
      Cholera: invasion of the intestinal epithelial barrier by a stably folded protein
      toxin.
AB  - Cholera toxin (CT) produced by Vibrio cholerae is the virulence factor
      responsible for the massive secretory diarrhea seen in Asiatic cholera. To cause
      disease, CT enters the intestinal epithelial cell as a stably folded protein by
      co-opting a lipid-based membrane receptor, ganglioside G(M1). G(M1) sorts the
      toxin into lipid rafts and a retrograde trafficking pathway to the endoplasmic
      reticulum, where the toxin unfolds and transfers its enzymatic subunit to the
      cytosol, probably by dislocation through the translocon sec61p. The molecular
      determinants that drive entry of CT into this pathway are encoded entirely within
      the structure of the protein toxin itself.

PMID- 11292585
TI  - Receptors and transmission in the brain-gut axis: potential for novel therapies.
      I. Receptors on visceral afferents.
AB  - Visceral afferents are the information superhighway from the gut to the central
      nervous system. These sensory nerves express a wide range of membrane receptors
      that can modulate their sensitivity. In this themes article, we concentrate on
      those receptors that enhance the excitability of visceral afferent neurons. Some
      receptors are part of a modality-specific transduction pathway involved in
      sensory signaling. Others, which are activated by substances derived from
      multiple cellular sources during ischemia, injury, or inflammation, act in a
      synergistic fashion to cause acute or chronic sensitization of the afferent
      nerves to mechanical and chemical stimuli. Such hypersensitivity is the hallmark
      of conditions such as irritable bowel syndrome. Accordingly, these receptors
      represent a rational target for drug treatments aimed at attenuating both the
      inappropriate visceral sensation and the aberrant reflex activity that are the
      foundation for alterations in bowel function.

PMID- 11292586
TI  - P2Y(11), a purinergic receptor acting via cAMP, mediates secretion by pancreatic
      duct epithelial cells.
AB  - Pancreatic duct epithelial cells (PDEC) mediate the exocrine secretion of fluid
      and electrolytes. We previously reported that ATP and UTP interact with P2Y(2)
      receptors on nontransformed canine PDEC to increase intracellular free Ca2+
      concentration ([Ca2+](i)) and stimulate Ca2+-activated Cl- and K+ channels. We
      now report that ATP interacts with additional purinergic receptors to increase
      cAMP and activate Cl- channels. ATP, 2-methylthio-ATP, and ATP-gamma-S stimulated
      a 4- to 10-fold cAMP increase with EC(50) of 10-100 microM. Neither UTP nor
      adenosine stimulated a cAMP increase, excluding a role for P2Y(2) or P1
      receptors. Although UTP stimulated an (125)I(-) efflux that was fully inhibited
      by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)
      ester (BAPTA-AM), ATP stimulated a partially resistant efflux, suggesting
      activation of additional Cl- conductances through P2Y(2)-independent and Ca2+
      independent pathways. In Ussing chambers, increased cAMP stimulated a much larger
      short-circuit current (I(sc)) increase from basolaterally permeabilized PDEC
      monolayers than increased [Ca2+](i). Luminal ATP and UTP and serosal UTP
      stimulated a small Ca2+-type I(sc) increase, whereas serosal ATP stimulated a
      large cAMP-type I(sc) response. Serosal ATP effect was inhibited by P2 receptor
      blockers and unaffected by BAPTA-AM, supporting ATP activation of Cl-
      conductances through P2 receptors and a Ca2+-independent pathway. RT-PCR
      confirmed the presence of P2Y(11) receptor mRNA, the only P2Y receptor acting via
      cAMP.

PMID- 11292587
TI  - Kupffer cell-derived cyclooxygenase-2 regulates hepatocyte Bcl-2 expression in
      choledocho-venous fistula rats.
AB  - We have previously demonstrated that after bile duct ligation hepatocytes express
      Bcl-2, although the mechanisms regulating Bcl-2 expression were not identified.
      Our aim was to determine if biliary constituents induce hepatocellular expression
      of Bcl-2 by a cyclooxygenase-2 (COX-2)-dependent mechanism. We used the
      choledocho-venous fistula (CVF) rat model for these studies and inhibited COX-2
      by feeding the animals nimesulide, a selective inhibitor of COX-2 activity. Serum
      bile acids were 70-fold greater in CVF animals compared with controls, although
      liver histology and serum alanine aminotransferase values remained normal for the
      duration of the study. Neither Bcl-2 nor COX-2 was detected in sham-operated
      animals. However, Bcl-2 was expressed in hepatocytes but not in other liver cells
      in the CVF animals. In contrast, COX-2 protein was identified in Kupffer cells
      but not in hepatocytes of CVF animals. Hepatic Bcl-2 protein expression was
      fourfold lower in the livers from nimesulide-treated CVF rats. In conclusion,
      high circulating concentrations of biliary constituents are associated with
      stimulation of de novo hepatocyte expression of Bcl-2 and Kupffer cell expression
      of COX-2. These data suggest Kupffer cell-derived prostanoids may regulate Bcl-2
      expression in the hepatocyte.

PMID- 11292588
TI  - Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL
      but not endotoxin mediated.
AB  - Recent studies from our laboratory demonstrated that mucosal lymphoid tissue such
      as Peyer's patch cells and lamina propria (LP) B lymphocytes from mice shows
      evidence of increased apoptosis after sepsis that is associated with localized
      inflammation/activation. The mechanism for this is poorly understood. Endotoxin
      as well as Fas/Fas ligand (FasL) have been shown to augment lymphocyte apoptosis;
      however, their contribution to the increase of apoptosis in LP B-cells during
      sepsis is not known. To study this, sepsis was induced by cecal ligation and
      puncture (CLP) in endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ-FasL(gld)
      (FasL(-)) mice and LP lymphocytes were isolated 24 h later. Phenotypic,
      apoptotic, and functional indexes were assessed. The number of LP B cells
      decreased markedly in C3H/HeJ mice but not in FasL-deficient animals at 24 h
      after CLP. This was associated with comparable alteration in apoptosis and Fas
      antigen expression in the B cells of these mice. Septic LP lymphocytes also
      showed increased IgA production, which was absent in the FasL-deficient CLP mice.
      Furthermore, Fas ligand deficiency appeared to improve survival of septic
      challenge. These data suggest that the increase in B cell apoptosis in septic
      animals is partially due to a Fas/FasL-mediated process but not endotoxin.

PMID- 11292589
TI  - Effects of systemic arterial hypoperfusion on splanchnic hemodynamics and hepatic
      arterial buffer response in pigs.
AB  - The hepatic arterial buffer response (HABR) tends to maintain liver blood flow
      under conditions of low mesenteric perfusion. We hypothesized that systemic
      hypoperfusion impairs the HABR. In 12 pigs, aortic blood flow was reduced by
      cardiac tamponade to 50 ml. kg(-1). min(-1) for 1 h (short-term tamponade) and
      further to 30 ml. kg(-1). min(-1) for another hour (prolonged tamponade). Twelve
      pigs without tamponade served as controls. Portal venous blood flow decreased
      from 17 +/- 3 (baseline) to 6 +/- 4 ml. kg(-1). min(-1) (prolonged tamponade; P =
      0.012) and did not change in controls, whereas hepatic arterial blood flow
      decreased from 2 +/- 1 (baseline) to 1 +/- 1 ml. kg(-1). min(-1) (prolonged
      tamponade; P = 0.050) and increased from 2 +/- 1 to 4 +/- 2 ml. kg(-1). min(-1)
      in controls (P = 0.002). The change in hepatic arterial conductance (DeltaC(ha))
      during acute portal vein occlusion decreased from 0.1 +/- 0.05 (baseline) to 0 +/
      0.01 ml. kg(-1). min(-1). mmHg(-1) (prolonged tamponade; P = 0.043). In
      controls, DeltaC(ha) did not change. Hepatic lactate extraction decreased, but
      hepatic release of glutathione S-transferase A did not change during cardiac
      tamponade. In conclusion, during low systemic perfusion, the HABR is exhausted
      and hepatic function is impaired without signs of cellular damage.

PMID- 11292590
TI  - Key role of PKC and Ca2+ in EGF protection of microtubules and intestinal barrier
      against oxidants.
AB  - Using monolayers of human intestinal (Caco-2) cells, we showed that growth
      factors (GFs) protect microtubules and barrier integrity against oxidative
      injury. Studies in nongastrointestinal cell models suggest that protein kinase C
      (PKC) signaling is key in GF-induced effects and that cytosolic calcium
      concentration ([Ca2+](i)) is essential in cell integrity. We hypothesized that GF
      protection involves activating PKC and maintaining normal ([Ca2+](i)) Monolayers
      were pretreated with epidermal growth factor (EGF) or PKC or Ca2+ modulators
      before exposure to oxidants (H2O2 or HOCl). Oxidants disrupted microtubules and
      barrier integrity, and EGF protected from this damage. EGF caused rapid
      distribution of PKC-alpha, PKC-betaI, and PKC-zeta isoforms to cell membranes,
      enhancing PKC activity of membrane fractions while reducing PKC activity of
      cytosolic fractions. EGF enhanced (45)Ca2+ efflux and prevented oxidant-induced
      (sustained) rises in ([Ca2+](i)). PKC inhibitors abolished and PKC activators
      mimicked EGF protection. Oxidant damage was mimicked by and potentiated by a Ca2+
      ionophore (A-23187), exacerbated by high-Ca2+ media, and prevented by calcium
      removal or chelation or by Ca2+ channel antagonists. PKC activators mimicked EGF
      on both (45)Ca2+ efflux and ([Ca2+](i)). Membrane Ca2+-ATPase pump inhibitors
      prevented protection by EGF or PKC activators. In conclusion, EGF protection of
      microtubules and the intestinal epithelial barrier requires activation of PKC
      signal transduction and normalization of ([Ca2+](i)).

PMID- 11292591
TI  - Assessment of antral grinding of a model solid meal with echo-planar imaging.
AB  - Mathematical modeling of how physical factors alter gastric emptying is limited
      by lack of precise measures of the forces exerted on gastric contents. We have
      produced agar gel beads (diameter 1.27 cm) with a range of fracture strengths
      (0.15-0.90 N) and assessed their breakdown by measuring their half-residence time
      (RT(1/2)) using magnetic resonance imaging. Beads were ingested either with a
      high (HV)- or low (LV)-viscosity liquid nutrient meal. With the LV meal, RT(1/2)
      was similar for bead strengths ranging from 0.15 to 0.65 N but increased from 22
      +/- 2 min (bead strength <0.65 N) to 65 +/- 12 min for bead strengths >0.65 N.
      With the HV meal, emptying of the harder beads was accelerated. The sense of
      fullness after ingesting the LV meal correlated linearly (correlation coefficient
      = 0.99) with gastric volume and was independently increased by the harder beads,
      which were associated with an increased antral diameter. We conclude that the
      maximum force exerted by the gastric antrum is close to 0.65 N and that gastric
      sieving is impaired by HV meals.

PMID- 11292592
TI  - Modulation of gastric motor activity by a centrally acting stimulus, circular
      vection, in humans.
AB  - The aims of this study were to investigate gastric motor correlates of vection, a
      centrally acting stimulus, and relate these responses to the induction of motion
      sickness symptoms. Antral contractile activity and gastric volume retained after
      a liquid nutrient meal (600 ml) were assessed by magnetic resonance imaging in
      healthy subjects during two different protocols. Vection was induced by an
      optokinetic drum, and subjects repeatedly rated the intensity of vection and
      nausea on 0-10 analog scales. Vection delayed gastric emptying [99% (89-102%)
      [median (interquartile ranges)] of volume retained at 28 min; control situation:
      79% (69-81%), P < 0.05]. Antral contractile activity followed a distinct time
      course of rapid decrease [-64% (-72 to -59%) change from baseline activity]
      immediately after onset of drum rotation followed by gradual recovery upon
      withdrawal of the stimulus. No relationship was found between the severity of
      nausea and inhibition of gastric emptying or antral contractile activity. The
      inhibition of antral contractile activity appears to be a good measure of the
      peripheral response to vection but is probably independent of subjective symptom
      induction.

PMID- 11292593
TI  - Endotoxin-induced reduction in biliary indocyanine green excretion rate in a
      chronically catheterized rat model.
AB  - Using a nonstressed chronically catheterized rat model in which the common bile
      duct was cannulated, we studied endotoxin-induced alterations in hepatic function
      by measuring changes in the maximal steady-state biliary excretion rate of the
      anionic dye indocyanine green (ICG). Biliary excretion of ICG was calculated from
      direct measurements of biliary ICG concentrations and the bile flow rate during a
      continuous vascular infusion of ICG. Despite significant elevations in mean peak
      serum tumor necrosis factor-alpha (TNF-alpha) concentrations (90.9 +/- 16.2
      ng/ml), there was no effect on mean rates of bile flow or biliary ICG clearance
      after administration of 100 microg/kg endotoxin at 6 or 24 h. Significant
      differences from mean baseline rates of bile flow and biliary ICG excretion did
      occur after administration of 1,000 microg/kg endotoxin (mean peak TNF-alpha
      129.6 +/- 24.4 ng/ml). Furthermore, when rats were treated with up to 16
      microg/kg of recombinant TNF-alpha, there was no change in mean rates of bile
      flow or ICG biliary clearance compared with baseline values. These data suggest
      that the complex regulation of biliary excretion is not mediated solely by TNF
      alpha.

PMID- 11292594
TI  - Staphylococcal enterotoxin B potentiates LPS-induced hepatic dysfunction in
      chronically catheterized rats.
AB  - Most models of liver dysfunction in sepsis use endotoxin (lipopolysaccharide;
      LPS) to induce a pathophysiological response. In our study published in this
      issue (Beno DWA, Uhing MR, Goto M, Chen Y, Jiyamapa-Serna VA, and Kimura RE. Am J
      Physiol Gastrointest Liver Physiol 280: G858-G865, 2001), the adverse effect of
      LPS on hepatic function in vivo was only significant at relatively high LPS doses
      despite high tumor necrosis factor-alpha concentrations. However, many patients
      with sepsis are exposed to multiple bacterial toxins that may augment the immune
      response, resulting in increased hepatic dysfunction. We have developed a model
      of polymicrobial sepsis by parentally administering a combination of
      staphylococcal enterotoxin B (SEB) and LPS. Using this model, we demonstrate that
      SEB (50 microg/kg) potentiates the effect of LPS-induced hepatic dysfunction as
      measured by decreased rates of biliary indocyanine green clearance and bile flow.
      These increases were most pronounced with doses of 10 and 100 microg/kg LPS,
      doses that by themselves do not induce hepatic dysfunction. This may explain the
      seemingly increased incidence and severity of liver dysfunction in sepsis, and it
      suggests that the exclusive use of LPS for replicating septic shock may not be
      relevant for studies of hepatic dysfunction.

PMID- 11292595
TI  - Ontogeny of hepatic enzymes involved in serine- and folate-dependent one-carbon
      metabolism in rabbits.
AB  - Serine occupies a central position in folate-dependent, one-carbon metabolism
      through 5,10-methylenetetrahydrofolate (MTHF) and 5-formyltetrahydrofolate
      (FTHF). We characterized the ontogeny of the specific activity of key enzymes
      involved in serine, 5,10-MTHF, and 5-FTHF metabolism: methenyltetrahydrofolate
      synthetase (MTHFS), MTHF reductase (MTHFR), the glycine cleavage system (GCS),
      methionine synthase (MS), and serine hydroxymethyltransferase (SHMT) in rabbit
      liver, placenta, brain, and kidney. In liver, MTHFS activity is low in the fetus
      (0.36 +/- 0.07 nmol. min(-1). mg protein(-1)), peaks at 3 wk (1.48 +/- 0.50 nmol.
      min(-1). mg protein(-1)), and then decreases to adult levels (1.13 +/- 0.32 nmol.
      min(-1). mg protein(-1)). MTHFR activity is highest early in gestation (24.9 +/-
      2.4 nmol. h(-1). mg protein(-1)) and declines rapidly by birth (4.7 +/- 1.3 nmol.
      h(-1). mg protein(-1)). MS is highest during fetal life and declines after birth.
      Cytosolic SHMT activity does not vary during development, but mitochondrial SHMT
      peaks at 23 days. GCS activity is high in the fetus and the neonate, declining
      after weaning. In placenta and brain, all activities are low throughout
      gestation. Cytosolic and mitochondrial SHMT activities are low in kidney and rise
      after weaning, whereas MTHFS is low throughout development. These data suggest
      that the liver is the primary site of activity for these enzymes. Throughout
      development, there are multiple potential sources for production of 5,10-MTHF,
      but early in gestation high MTHFR activity and low MTHFS activity could reduce
      5,10-MTHF availability.

PMID- 11292596
TI  - In vivo recognition of mannosylated proteins by hepatic mannose receptors and
      mannan-binding protein.
AB  - In vivo recognition of mannosylated proteins by hepatic mannose receptors and
      serum mannan-binding protein (MBP) was investigated in mice. After intravenous
      administration, all three different (111)In-mannosylated proteins were taken up
      mainly by liver, and uptake was saturated with increasing doses. (111)In-Man
      superoxide dismutases and (111)In-Man(12)- and (111)In-Man(16)-BSA had simple
      dose-dependent pharmacokinetic profiles, whereas other derivatives ((111)In
      Man(25)-, -Man(35)-, and -Man(46)-BSA and (111)In-Man-IgGs) showed slow hepatic
      uptake at <1 mg/kg. Purified MBP experiments in vitro indicated that these
      derivatives bind to MBP in serum after injection, which interferes with their
      hepatic uptake. To quantitatively evaluate these recognition properties in vivo,
      a pharmacokinetic model-based analysis was performed for (111)In-Man-BSAs,
      estimating some parameters, including the Michaelis-Menten constant of the
      hepatic uptake and the dissociation constant of MBP, which correlate to the
      affinity of Man-BSAs for mannose receptors and MBP, respectively. The
      dissociation constant of Man-BSA and MBP decreased dramatically with increasing
      density of mannose, but the Michaelis-Menten constant of hepatic uptake of Man
      BSA was not so sensitive to the change in density. This suggests that the in vivo
      recognition of MBP has a stronger cluster effect than that of mannose receptors.
      Differences obtained here are due to the unique arrangement of carbohydrate
      recognition domains on each mannose-specific lectin available for mannosylated
      ligand recognition.

PMID- 11292597
TI  - MEK inhibits secretin release and pancreatic secretion: roles of secretin
      releasing peptide and somatostatin.
AB  - We investigated the mechanism of action of methionine enkephalin (MEK) on HCl
      stimulated secretin release and pancreatic exocrine secretion. Anesthetized rats
      with pancreatobiliary cannulas and isolated upper small intestinal loops were
      perfused intraduodenally with 0.01 N HCl while bile and pancreatic juice were
      diverted. The effect of intravenous MEK on acid-stimulated secretin release and
      pancreatic exocrine secretion was then studied with or without coinfusion of
      naloxone, an anti-somatostatin (SS) serum, or normal rabbit serum. Duodenal acid
      perfusate, which contains secretin-releasing peptide (SRP) activity, was
      collected from donor rats with or without pretreatment with MEK, MEK + naloxone,
      or MEK + anti-SS serum, concentrated by ultrafiltration, and neutralized. The
      concentrated acid perfusate (CAP), which contains SRP bioactivity, was infused
      intraduodenally into recipient rats. MEK increased plasma SS concentration and
      inhibited secretin release and pancreatic fluid and bicarbonate secretion dose
      dependently. The inhibition was partially reversed by naloxone and anti-SS serum
      but not by normal rabbit serum. In recipient rats, CAP increased plasma secretin
      level and pancreatic secretion. CAP SRP bioactivity decreased when it was
      collected from MEK-treated donor rats; this was partially reversed by coinfusion
      with naloxone or anti-SS serum. These results suggest that in the rat, MEK
      inhibition of acid-stimulated pancreatic secretion and secretin release involves
      suppression of SRP activity release. Thus the MEK inhibitory effect appears to be
      mediated in part by endogenous SS.

PMID- 11292598
TI  - Gastroprotective and vasodilatory effects of epidermal growth factor: the role of
      sensory afferent neurons.
AB  - Epidermal growth factor (EGF) has been shown to exert gastric hyperemic and
      gastroprotective effects via capsaicin-sensitive afferent neurons, including the
      release of calcitonin gene-related peptide (CGRP). We examined the protective and
      vasodilatory effects of EGF on the gastric mucosa and its interaction with
      sensory nerves, CGRP, and nitric oxide (NO) in anesthetized rats. Intragastric
      EGF (10 or 30 microg) significantly reduced gastric mucosal lesions induced by
      intragastric 60% ethanol (50.6% by 10 microg EGF and 70.0% by 30 microg EGF). The
      protective effect of EGF was significantly inhibited by pretreatment with
      capsaicin desensitization, human CGRP1 antagonist hCGRP-(8-37), or N(omega)-nitro
      L-arginine methyl ester (L-NAME). Intravital microscopy showed that topically
      applied EGF (10-1,000 microg/ml) dilated the gastric mucosal arterioles dose
      dependently and that this vasodilatory effect was significantly inhibited by
      equivalent pretreatments. These findings suggest that EGF plays a protective role
      against ethanol-induced gastric mucosal injury, possibly by dilating the gastric
      mucosal arterioles via capsaicin-sensitive afferent neurons involving CGRP and NO
      mechanisms.

PMID- 11292599
TI  - Intraluminal modulation of gastric sensitivity to distension: effects of
      hydrochloric acid and meal.
AB  - Conscious sensations in response to gut distensions may be modulated by
      temporospatial interactions among different stimuli. This study investigated
      whether symptoms induced by gastric distension may be modified by hydrochloric
      acid (HCl) gastric infusion and meal ingestion. In nine healthy subjects, fixed
      pressure (isobaric) and fixed volume (isovolumetric) distensions were performed
      during continuous (4 ml/min) intragastric saline or HCl infusion, during fasting
      and after meal ingestion, until the maximal distension step defined as discomfort
      or a predefined maximal volume. During fasting isobaric distensions, the maximal
      distension step was significantly decreased during HCl compared with saline. The
      intragastric volumes were not significantly different, but the wall tension was
      significantly lower during HCl than saline. HCl increased gastric compliance.
      Meal ingestion relaxed the stomach and decreased the pressure at the maximal
      distension step during saline, but HCl did not further decrease it compared with
      fasting. During isovolumetric distensions, HCl also increased gastric compliance,
      but in both fasted and fed states it did not modify the maximal distension steps.
      In conclusion, sensations in response to gastric isobaric distensions, but not to
      isovolumetric distensions, are influenced by gastric acid infusion and meal
      ingestion. The effects of HCl might be related to a sensitization of mucosal
      mechanoreceptors.

PMID- 11292600
TI  - HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line.
AB  - The regulation of intercellular adhesion by hepatocyte growth factor (HGF) was
      examined on a novel nontumorigenic gastric epithelial cell line (IMGE-5) derived
      from H-2Kb-tsA58 transgenic mice. IMGE-5 cells constitutively expressed
      cytokeratin 18 and HGF receptors. Under permissive conditions (33 degrees C +
      interferon-gamma), IMGE-5 cells proliferated rapidly but did not display membrane
      expression of adherens and tight junction proteins. Under nonpermissive
      conditions, their proliferation was decreased and they displayed a strong,
      localized membrane expression of E-cadherin/beta-catenin and occludin/ZO-1. HGF
      treatment largely prevented the targeting of ZO-1 to the tight junction and
      induced a significant decrease of the transepithelial resistance measured across
      a confluent IMGE-5 cell monolayer. HGF rapidly increased the tyrosine
      phosphorylation of ZO-1 and decreased its association with occludin in a
      phosphatidylinositol 3-kinase (PI 3-kinase)-dependent manner. PI 3-kinase was
      also involved in HGF-induced migration of IMGE-5 cells. Our results demonstrate
      that 1) HGF prevents the appearance of ZO-1 in the membrane during epithelial
      cell differentiation; 2) HGF causes partial relocalization of ZO-1 to the
      cytoplasm and nucleus and concomitantly stimulates cell dissociation and
      migration; and 3) IMGE-5 cells offer a useful model for the study of gastric
      epithelial cell differentiation.

PMID- 11292601
TI  - The adherent gastrointestinal mucus gel layer: thickness and physical state in
      vivo.
AB  - Divergent results from in vitro studies on the thickness and appearance of the
      gastrointestinal mucus layer have previously been reported. With an in vivo
      model, we studied mucus gel thickness over time from stomach to colon. The
      gastrointestinal tissues of Inactin-anesthetized rats were mounted luminal side
      up for intravital microscopy. Mucus thickness was measured with a micropipette
      before and after mucus removal by suction. The mucus layer was translucent and
      continuous; it was thickest in the colon (approximately 830 microm) and thinnest
      in the jejunum (approximately 123 microm). On mucus removal, a continuous, firmly
      adherent mucus layer remained attached to the epithelial surface in the corpus
      (approximately 80 microm), antrum (approximately 154 microm), and colon
      (approximately 116 microm). In the small intestine, this layer was very thin
      (approximately 20 microm) or absent. After mucus removal, there was a continuous
      increase in mucus thickness with the highest rate in the colon and the lowest
      rate in the stomach. In conclusion, the adherent gastrointestinal mucus gel in
      vivo is continuous and can be divided into two layers: a loosely adherent layer
      removable by suction and a layer firmly attached to the mucosa.

PMID- 11292602
TI  - Upregulation of iNOS by COX-2 in muscularis resident macrophage of rat intestine
      stimulated with LPS.
AB  - We investigated the effect of lipopolysaccharide (LPS) on the induction of
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in muscularis
      resident macrophages of rat intestine in situ. When the tissue was incubated with
      LPS for 4 h, mRNA levels of iNOS and COX-2 were increased. The majority of iNOS
      and COX-2 proteins appeared to be localized to the dense network of muscularis
      resident macrophages immunoreactive to ED2. LPS treatment also increased the
      production of nitric oxide (NO), PGE(2), and PGI(2). The increased expression of
      iNOS mRNA by LPS was suppressed by indomethacin but not by N(G)-monomethyl-L
      arginine (L-NMMA). The increased expression of COX-2 mRNA by LPS was affected
      neither by indomethacin nor by L-NMMA. Muscle contractility stimulated by 3
      microM carbachol was significantly inhibited in the LPS-treated muscle, which was
      restored by treatment of the tissue with L-NMMA, aminoguanidine, indomethacin, or
      NS-398. Together, these findings show that LPS increases iNOS expression and
      stimulates NO production in muscularis resident macrophages to inhibit smooth
      muscle contraction. LPS-induced iNOS gene expression may be mediated by autocrine
      regulation of PGs through the induction of COX-2 gene expression.

PMID- 11292603
TI  - Chronic ethanol consumption exacerbates microcirculatory damage in rat mesentery
      after reperfusion.
AB  - Although the negative effect of excessive alcohol consumption on later stressful
      events has long been recognized, pathophysiological mechanisms are incompletely
      understood. We examined possible roles of oxygen radicals and glutathione content
      in mesenteric venules of chronically ethanol-fed rats exposed to ischemia
      reperfusion. Changes in microvascular hemodynamics, such as red blood cell (RBC)
      velocity, leukocyte adherence, and albumin extravasation, were monitored in
      postcapillary venules by intravital fluorescence microscopy. Chronic ethanol
      feeding significantly exaggerated the magnitude of the decrease in RBC velocity,
      the increased number of adherent leukocytes, and increased albumin leakage
      elicited by 10 min of ischemia followed by 30 min of reperfusion. Oxidative
      stress in the endothelium of venules monitored by dihydrorhodamine 123 (DHR)
      fluorescence was more severe in rats fed ethanol chronically. Both superoxide
      dismutase and N-acetyl-L-cysteine, which is known to increase glutathione
      content, reduced the ischemia-reperfusion-induced decrease in RBC velocity, the
      number of adherent leukocytes, and the increase in albumin leakage, as well as
      oxidative activation of DHR. This suggests that the increased reperfusion-induced
      microvascular disturbances in the mesenteric venules of rats fed ethanol
      chronically are significantly correlated with excessive production of oxygen
      derived free radicals and decreased glutathione synthesis.

PMID- 11292604
TI  - Alterations in spontaneous contractions in vitro after repeated inflammation of
      rat distal colon.
AB  - In inflammatory bowel disease, smooth muscle function reportedly varies with
      disease duration. The aim of these studies was to determine changes in the
      control of spontaneous contractions in a model of experimental colitis that
      included reinflammation of the healed area. The amplitude and frequency of
      spontaneous contractions in circular smooth muscle were determined after
      intrarectal administration of trinitrobenzenesulfonic acid in rat distal colon.
      With the use of a novel paradigm, rats were studied 4 h (acute) or 28 days
      (healed) after the initial inflammation. At 28 days, rats were studied 4 h after
      a second inflammation (reinflamed) of the colon. Colitis induced transient
      increases in the amplitude of spontaneous contractions coincident with a loss of
      nitric oxide synthase activity. The frequency of contractions was controlled by
      constitutive nitric oxide in controls. Frequency was increased in healed and
      reinflamed colon and was associated with a shift in the dominance of neural
      constitutive nitric oxide synthase control to that of inducible nitric oxide
      synthase (iNOS). The initial colitis induced a remodeling of the neural control
      of spontaneous contractions reflecting changes in their regulation by
      constitutive nitric oxide synthase and iNOS.

PMID- 11292606
TI  - Compensatory hepatic regeneration after mild, but not fulminant, intraperitoneal
      sepsis in rats.
AB  - Sepsis is the leading cause of death in surgical intensive care units. Although
      both mild sepsis secondary to cecal ligation and single puncture (CLP) and
      fulminant, double puncture CLP (2CLP) may provoke hepatocyte death, we
      hypothesize that regeneration compensates for cell death after CLP but not 2CLP.
      In male Sprague-Dawley rats, hepatic necrosis, as determined by serum alpha
      glutathione S-transferase (alpha-GST) levels, was significantly but equally
      elevated over time after both CLP and 2CLP. Apoptosis, evaluated using both
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and
      morphological examination, was minimal after both CLP and 2CLP. Regeneration,
      assayed by staining tissue for incorporation of exogenously administered
      bromodeoxyuridine, was present after CLP but not after 2CLP. To further
      substantiate impaired regeneration, steady-state levels of mRNAs encoding JunB,
      LRF-1, and cyclin D1 were determined. After 2CLP, the absence of JunB, LRF-1, and
      cyclin D1 mRNAs confirmed failed activation of the mitogen-activated protein
      kinase-linked proliferative pathway and progression through the cell cycle.
      Therefore, failed hepatocyte regeneration may be a manifestation of hepatic
      dysfunction in fulminant sepsis.

PMID- 11292605
TI  - Expression of apoptosis on rat liver by hepatic vagus hyperactivity after
      ventromedial hypothalamic lesioning.
AB  - We examined whether the Fas (APO-1/CD95)/Fas ligand system mediates apoptosis in
      rats with ventromedial hypothalamus (VMH) lesions. Northern and Western blotting
      indicated that VMH lesions lead to a significant increase in Fas mRNA and protein
      expression from day 1 to day 7 and in Fas ligand mRNA and protein expression from
      day 2 to day 7. Immunohistochemistry indicated that the region of strongest Fas
      expression shifted from acinar zone 1 to zones 2 and 3 by day 7 after VMH
      lesioning and that at days 2-7 Fas-ligand-positive hepatocyte cell membranes and
      cytoplasm were randomly distributed in acinar zones 1-3. We also analyzed
      activation of caspase 3-like proteases in hepatocytes, Kupffer cells, and
      sinusoidal endothelial cells. Spectrofluorometric assay demonstrated that caspase
      3-like activity significantly increased only in hepatocytes after VMH lesioning.
      Moreover, electron microscopy and TUNEL assay showed that VMH lesions induced
      apoptosis. All of these effects were completely inhibited by hepatic vagotomy and
      administration of atropine. Vagal firing after VMH lesioning may stimulate
      Fas/Fas ligand system-mediated apoptosis through the cholinergic system in the
      rat liver.

PMID- 11292607
TI  - Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis
      and associated lung injury.
AB  - Complement factor C5a acting via C5a receptors (C5aR) is recognized as an
      anaphylotoxin and chemoattractant that exerts proinflammatory effects in many
      pathological states. The effects of C5a and C5aR in acute pancreatitis and in
      pancreatitis-associated lung injury were evaluated using genetically altered mice
      that either lack C5aR or do not express C5. Pancreatitis was induced by
      administration of 12 hourly injections of cerulein (50 microg/kg ip). The
      severity of pancreatitis was determined by measuring serum amylase, neutrophil
      sequestration in the pancreas, and acinar cell necrosis. The severity of lung
      injury was evaluated by measuring neutrophil sequestration in the lung and
      pulmonary microvascular permeability. In both strains of genetically altered
      mice, the severity of pancreatitis and pancreatitis-associated lung injury was
      greater than that noted in the comparison wild-type strains of C5aR- and C5
      sufficient animals. This exacerbation of injury in the absence of C5a function
      indicates that, in pancreatitis, C5a exerts an anti-inflammatory effect.
      Potentially, C5a and its receptor are capable of both promoting and reducing the
      extent of acute inflammation.

PMID- 11292608
TI  - Intracisternal TRH analog induces Fos expression in gastric myenteric neurons and
      glia in conscious rats.
AB  - Activation of gastric myenteric cells by intracisternal injection of the stable
      thyrotropin-releasing hormone (TRH) analog RX-77368, at a dose inducing near
      maximal vagal cholinergic stimulation of gastric functions, was investigated in
      conscious rats. Fos immunoreactivity was assessed in gastric longitudinal muscle
      myenteric plexus whole mount preparations 90 min after intracisternal injection.
      Fos-immunoreactive cells were rare in controls (~1 cell/ganglion), whereas
      intracisternal RX-77368 (50 ng) increased the number to 24.8 +/- 1.8 and 26.8 +/-
      2.2 cells/ganglion in the corpus and antrum, respectively. Hexamethonium (20
      mg/kg sc) prevented Fos expression by 90%, whereas atropine (2 mg/kg sc) had no
      effect. The neuronal marker protein gene product 9.5 and the glial markers S-100
      and glial fibrillary acidic proteins showed that RX-77368 induced Fos in both
      myenteric neurons and glia. Vesicular ACh transporter and calretinin were
      detected around the activated myenteric neurons. These results indicated that
      central vagal efferent stimulation by intracisternal RX-77368 activates gastric
      myenteric neurons as well as glial cells mainly through nicotinic ACh receptors
      in conscious rats.

PMID- 11292609
TI  - NF-kappaB activation and susceptibility to apoptosis after polyamine depletion in
      intestinal epithelial cells.
AB  - The maintenance of intestinal mucosal integrity depends on a balance between cell
      renewal and cell death, including apoptosis. The natural polyamines, putrescine,
      spermidine, and spermine, are essential for mucosal growth, and decreasing
      polyamine levels cause G(1) phase growth arrest in intestinal epithelial (IEC-6)
      cells. The present study was done to determine changes in susceptibility of IEC-6
      cells to apoptosis after depletion of cellular polyamines and to further
      elucidate the role of nuclear factor-kappaB (NF-kappaB) in this process. Although
      depletion of polyamines by alpha-difluoromethylornithine (DFMO) did not directly
      induce apoptosis, the susceptibility of polyamine-deficient cells to
      staurosporine (STS)-induced apoptosis increased significantly as measured by
      changes in morphological features and internucleosomal DNA fragmentation. In
      contrast, polyamine depletion by DFMO promoted resistance to apoptotic cell death
      induced by the combination of tumor necrosis factor-alpha (TNF-alpha) and
      cycloheximide. Depletion of cellular polyamines also increased the basal level of
      NF-kappaB proteins, induced NF-kappaB nuclear translocation, and activated the
      sequence-specific DNA binding activity. Inhibition of NF-kappaB binding activity
      by sulfasalazine or MG-132 not only prevented the increased susceptibility to STS
      induced apoptosis but also blocked the resistance to cell death induced by TNF
      alpha in combination with cycloheximide in polyamine-deficient cells. These
      results indicate that 1) polyamine depletion sensitizes intestinal epithelial
      cells to STS-induced apoptosis but promotes the resistance to TNF-alpha-induced
      cell death, 2) polyamine depletion induces NF-kappaB activation, and 3)
      disruption of NF-kappaB function is associated with altered susceptibility to
      apoptosis induced by STS or TNF-alpha. These findings suggest that increased NF
      kappaB activity after polyamine depletion has a proapoptotic or antiapoptotic
      effect on intestinal epithelial cells determined by the nature of the death
      stimulus.

PMID- 11292610
TI  - Diphenyleneiodonium sulfate, an NADPH oxidase inhibitor, prevents early alcohol
      induced liver injury in the rat.
AB  - The oxidant source in alcohol-induced liver disease remains unclear. NADPH
      oxidase (mainly in liver Kupffer cells and infiltrating neutrophils) could be a
      potential free radical source. We aimed to determine if NADPH oxidase inhibitor
      diphenyleneiodonium sulfate (DPI) affects nuclear factor-kappaB (NF-kappaB)
      activation, liver tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and
      early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat
      liquid diets with or without ethanol (10-16 g. kg(-1). day(-1)) continuously for
      up to 4 wk, using the Tsukamoto-French intragastric enteral feeding protocol. DPI
      or saline vehicle was administered by subcutaneous injection for 4 wk. Mean urine
      ethanol concentrations were similar between the ethanol- and ethanol plus DPI
      treated groups. Enteral ethanol feeding caused severe fat accumulation, mild
      inflammation, and necrosis in the liver (pathology score, 4.3 +/- 0.3). In
      contrast, DPI significantly blunted these changes (pathology score, 0.8 +/- 0.4).
      Enteral ethanol administration for 4 wk also significantly increased free radical
      adduct formation, NF-kappaB activity, and TNF-alpha expression in the liver. DPI
      almost completely blunted these parameters. These results indicate that DPI
      prevents early alcohol-induced liver injury, most likely by inhibiting free
      radical formation via NADPH oxidase, thereby preventing NF-kappaB activation and
      TNF-alpha mRNA expression in the liver.

PMID- 11292611
TI  - Desensitization of ileal vagal receptors by short-chain fatty acids in pigs.
AB  - Coloileal reflux episodes trigger specialized ileal motor activities and inhibit
      gastric motility in pigs. The initiation of these events requires the detection
      by the distal ileum of the invading colonic contents that differ from the ileal
      chyme primarily in short-chain fatty acid (SCFA) concentrations. In addition to
      the already described humoral pathway, this detection might also involve ileal
      vagal afferents. Sensitivity to SCFA of 12 ileal vagal units was investigated in
      anesthetized pigs with single-unit recording at the left cervical vagus. SCFA
      mixtures (0.35, 0.7, and 1.4 mol/l) containing acetic, propionic, and butyric
      acids in proportions identical to that in the porcine cecocolon were compared
      with isotonic and hypertonic saline. All units behaved as slowly adapting
      mechanoreceptors (half-adaptation time = 35.4 +/- 15.89 s), and their sensitivity
      to local mechanical probing was suppressed by local anesthesia; 7 units
      significantly decreased their spontaneous firing with 0.7 and 1.4 but not 0.35
      mol/l SCFA infusion compared with hypertonic or isotonic saline. Similarly, the
      response induced by distension in the same seven units was reduced (5 neurons) or
      abolished (2 neurons) after infusion of 0.7 (22.8 +/- 2.39 impulses/s) and 1.4
      (30.3 +/- 2.12 impulses/s) mol/l SCFA solutions compared with isotonic saline
      (38.6 +/- 4.09 impulses/s). These differences in discharge were not the result of
      changes in ileal compliance, which remained constant after SCFA. In conclusion,
      SCFA, at concentrations near those found during coloileal reflux episodes,
      reduced or abolished mechanical sensitivity of ileal vagal afferents.

PMID- 11292612
TI  - Insulin-like growth factor I and insulin-like growth factor binding protein 5 in
      Crohn's disease.
AB  - Insulin-like growth factor (IGF)-I and its binding protein IGF binding protein 5
      (IGFBP-5) were highly expressed in inflamed and fibrotic intestine in
      experimental Crohn's disease. IGF-I induced proliferation and increased collagen
      synthesis by smooth muscle cells and fibroblasts/myofibroblasts in vitro. Here we
      studied IGF-I and IGFBP-5 in Crohn's disease tissue. Tissue was collected from
      patients undergoing intestinal resection for Crohn's disease. IGF-I and IGFBP-5
      mRNAs were quantitated by RNase protection assay and Northern blot analysis,
      respectively. In situ hybridization was performed to localize mRNA expression,
      and Western immunoblot was performed to quantitate protein expression. IGF-I and
      IGFBP-5 mRNAs were increased in inflamed/fibrotic intestine compared with normal
      appearing intestine. IGF-I mRNA was expressed in multiple cell types in the
      lamina propria and fibroblast-like cells of the submucosa and muscularis externa.
      IGFBP-5 mRNA was highly expressed in smooth muscle of the muscularis mucosae and
      muscularis externa as well as fibroblast-like cells throughout the bowel wall.
      Tissue IGFBP-5 protein correlated with collagen type I (r = 0.82). These findings
      are consistent with a mechanism whereby IGF-I acts on smooth muscle and
      fibroblasts/myofibroblasts to increase collagen synthesis and cellular
      proliferation; its effects may be modulated by locally expressed IGFBP-5.

PMID- 11292613
TI  - Effect of Schistosoma mansoni-induced granulomatous inflammation on murine
      gastrointestinal motility.
AB  - In Schistosoma mansoni-infected mice, gastrointestinal transit was measured in
      vivo and the neuromuscular function of longitudinal muscle strips of inflamed
      ileum and noninflamed gastric fundus was assessed in vitro. Eight weeks after
      infection, the ileal wall was acutely inflamed, as shown by a mucosal
      inflammatory infiltrate, leading to an increase in mucosal thickness, in
      myeloperoxidase (MPO) activity, and in interleukin (IL)-1beta production. At that
      time, both gastrointestinal transit and in vitro ileal contractility were normal.
      Twelve weeks after infection, chronic granulomatous inflammation led to
      proliferation of the muscle layer and to a further increase in MPO activity,
      whereas IL-1beta production normalized. Gastrointestinal transit was decreased,
      whereas in vitro ileal contractility was increased irrespective of the
      contractile stimulus. In vitro incubation with IL-1beta (10 ng/ml for 60 min)
      significantly increased ileal contractility only at 8 wk after infection.
      Indomethacin, tetrodotoxin, and atropine had no differential effect on ileal
      contractility in controls and infected mice. In vitro contractility of
      noninflamed gastric fundus was normal both 8 and 12 wk after infection. We
      conclude that intestinal schistosomiasis 8 wk after infection is associated only
      with structural changes of the ileum, whereas 12 wk after infection, both
      structural and functional changes are present. These changes are characterized by
      increased ileal wall thickness, decreased gastrointestinal transit, and increased
      smooth muscle contractility restricted to the inflamed gut segment.

PMID- 11292614
TI  - Human biliary mucin binds to E-selectin: a possible role in modulation of
      inflammation.
AB  - E-selectin, expressed on endothelial cells, mediates adhesion of leukocytes and
      tumor cells to endothelium. CA19-9 (sialyl-Lewis(a)) and sialyl-Lewis(x) are
      specific ligands for E-selectin. We have recently shown that mucin-rich culture
      media from human gallbladder epithelial cells contains CA19-9. In this study, we
      have tested whether human biliary mucin binds to E-selectin. The ability of
      mucins to inhibit the adhesion of HL-60 cells to immobilized E-selectin was taken
      as an index for E-selectin binding. Gallbladder bile, hepatic bile, and culture
      medium from human gallbladder epithelial cells completely inhibited the adhesion
      of HL-60 cells to E-selectin. The mucin-rich fractions of human bile exhibited
      strong inhibition, whereas mucin-free fractions had little effect. In contrast to
      human bile samples, CA19-9-free medium from cultured dog gallbladder epithelial
      cells failed to inhibit HL-60 binding. Furthermore, after CA19-9 immunoaffinity
      chromatography, which selectively extracted CA19-9 from bile, bile samples showed
      poor inhibition of HL-60 adhesion to immobilized E-selectin. A good correlation
      was observed between E-selectin binding and CA 19-9 concentrations in bile. Our
      results show that human bile has E-selectin binding activity that is mediated by
      the CA19-9 side chain of biliary mucin.

PMID- 11292615
TI  - Function and spatial distribution of ion channels and transporters in cell
      migration.
AB  - Cell migration plays a central role in many physiological and pathophysiological
      processes, such as embryogenesis, immune defense, wound healing, or the formation
      of tumor metastases. Detailed models have been developed that describe
      cytoskeletal mechanisms of cell migration. However, evidence is emerging that ion
      channels and transporters also play an important role in cell migration. The
      purpose of this review is to examine the function and subcellular distribution of
      ion channels and transporters in cell migration. Topics covered will be a brief
      overview of cytoskeletal mechanisms of migration, the role of ion channels and
      transporters involved in cell migration, and ways by which a polarized
      distribution of ion channels and transporters can be achieved in migrating cells.
      Moreover, a model is proposed that combines ion transport with cytoskeletal
      mechanisms of migration.

PMID- 11292616
TI  - Ion permeation and selectivity in ClC-type chloride channels.
AB  - Voltage-gated anion channels are present in almost every living cell and have
      many physiological functions. Recently, a novel gene family encoding voltage
      gated chloride channels, the ClC family, was identified. The knowledge of primary
      amino acid sequences has allowed for the study of these anion channels in
      heterologous expression systems and made possible the combination of site
      directed mutagenesis and high-resolution electrophysiological measurements as a
      means of gaining insights into the molecular basis of channel function. This
      review focuses on one particular aspect of chloride channel function, the
      selective transport of anions through biological membranes. I will describe
      recent experiments using a combination of cellular electrophysiology, molecular
      genetics, and recombinant DNA technology to study the molecular basis of ion
      permeation and selection in ClC-type chloride channels. These novel tools have
      provided new insights into basic mechanisms underlying the function of these
      biologically important channels.

PMID- 11292617
TI  - Na+-alanine uptake activates a Cl- conductance in frog renal proximal tubule
      cells via nonconventional PKC.
AB  - Hyposmotically induced swelling of frog renal proximal tubule cells activates a
      DIDS-sensitive, outwardly rectifying Cl- conductance via a conventional protein
      kinase C (PKC). This study examines whether Na+-alanine cotransport similarly
      activates a DIDS-sensitive Cl- conductance in frog renal proximal tubule cells.
      On stimulation of Na+-alanine cotransport, the DIDS-sensitive current (I(DIDS
      Ala)) increased markedly over time. I(DIDS-Ala) exhibited outward rectification,
      a Na+/Cl- selectivity ratio of 0.19 +/- 0.03, and an anion selectivity sequence
      Br- = Cl- > I- > gluconate-. Activation of I(DIDS-Ala) was dependent on ATP
      hydrolysis and PKC-mediated phosphorylation and was inhibited by hyperosmotic
      conditions. Activation could be not ascribed to a conventional PKC isoform, as
      I(DIDS-Ala) was not affected by removing Ca2+ or by phorbol ester treatment,
      suggesting a role for a nonconventional PKC isoform, either novel or atypical. We
      conclude that Na+-alanine cotransport activates a DIDS-sensitive Cl- conductance
      via a nonconventional PKC isoform. This contrasts with the hyposmotically
      activated Cl- conductance, which requires conventional PKC activation.

PMID- 11292618
TI  - Long-term adaptation of renal cells to hypertonicity: role of MAP kinases and Na
      K-ATPase.
AB  - Renal cells in culture have low viability when exposed to hypertonicity. We
      developed cell lines of inner medullary collecting duct cells adapted to live at
      600 and 900 mosmol/kgH(2)O. We studied the three modules of the mitogen-activated
      protein (MAP) kinase family in the adapted cells. These cells had no increase in
      either extracellular signal-regulated kinase, c-Jun NH(2)-terminal kinase, or p38
      MAP kinase protein or basal activity. When acutely challenged with further
      increments in tonicity, they had blunted activation of these kinases, which was
      not due to enhanced phosphatase activity. In contrast, the cells adapted to the
      hypertonicity displayed a marked increment in Na-K-ATPase expression (5-fold) and
      ouabain-sensitive Na-K-ATPase activity (10-fold). The changes were reversible on
      return to isotonic conditions. Replacement of 300 mosmol/kgH(2)O of NaCl by urea
      in cells adapted to 600 mosmol/kgH(2)O resulted in marked decrement in Na-K
      ATPase and failure to maintain the cell line. Replacement of NaCl for urea in
      cells adapted to 900 mosmol/kgH(2)O did not alter either Na-K-ATPase expression,
      or the viability of the cells. The in vivo modulation of Na-K-ATPase was studied
      in the renal papilla of water-deprived mice (urinary osmolality 2,900
      mosmol/kgH(2)O), compared with that of mice drinking dextrose in water (550
      mosmol/kgH(2)O). Increased water intake was associated with a ~30% decrement in
      Na-K-ATPase expression (P < 0.02, n = 6), suggesting that this enzyme is
      osmoregulated in vivo. We conclude that whereas MAP kinases play a role in the
      response to acute changes in tonicity, they are not central to the chronic
      adaptive response. Rather, in this setting there is upregulation of other
      osmoprotective proteins, among which Na-K-ATPase appears to be an important
      component of the adaptive process.

PMID- 11292620
TI  - Flow-dependent K+ secretion in the cortical collecting duct is mediated by a maxi
      K channel.
AB  - K+ secretion by the cortical collecting duct (CCD) is stimulated at high flow
      rates. Patch-clamp analysis has identified a small-conductance secretory K+ (SK)
      and a high-conductance Ca(2+)-activated K+ (maxi-K) channel in the apical
      membrane of the CCD. The SK channel, encoded by ROMK, is believed to mediate
      baseline K+ secretion. The role of the stretch- and Ca2+-activated maxi-K channel
      is still uncertain. The purpose of this study was to identify the K+ channel
      mediating flow-dependent K+ secretion in the CCD. Segments isolated from New
      Zealand White rabbits were microperfused in the absence and presence of luminal
      tetraethylammonium (TEA) or charybdotoxin, both inhibitors of maxi-K but not SK
      channels, or apamin, an inhibitor of small-conductance maxi-K+ channels. Net K+
      secretion and Na+ absorption were measured at varying flow rates. In the absence
      of TEA, net K+ secretion increased from 8.3 +/- 1.0 to 23.4 +/- 4.7 pmol. min(
      1). mm(-1) (P < 0.03) as the tubular flow rate was increased from 0.5 to 6 nl.
      min(-1). mm(-1). Flow stimulation of net K+ secretion was blocked by luminal TEA
      (8.2 +/- 1.2 vs. 9.9 +/- 2.7 pmol. min(-1). mm(-1) at 0.6 and 6 nl. min(-1). mm(
      1) flow rates, respectively) or charybdotoxin (6.8 +/- 1.6 vs. 8.3 +/- 1.6 pmol.
      min(-1). mm(-1) at 1 and 4 nl. min(-1). mm(-1) flow rates, respectively) but not
      by apamin. These results suggest that flow-dependent K+ secretion is mediated by
      a maxi-K channel, whereas baseline K+ secretion occurs through a TEA- and
      charybdotoxin-insensitive SK (ROMK) channel.

PMID- 11292619
TI  - Contributions of angiotensin II and tumor necrosis factor-alpha to the
      development of renal fibrosis.
AB  - Angiotensin II upregulates tumor necrosis factor-alpha (TNF-alpha) in the rat
      kidney with unilateral ureteral obstruction (UUO). In a mouse model of UUO, we
      found that tubulointerstitial fibrosis is blunted when the TNF-alpha receptor,
      TNFR1, is functionally knocked out. In this study, we used mutant mice with UUO
      in which the angiotensin II receptor AT(1a) or the TNF-alpha receptors TNFR1 and
      TNFR2 were knocked out to elucidate interactions between the two systems. The
      contribution of both systems to renal fibrosis was assessed by treating
      TNFR1/TNFR2-double knockout (KO) mice with an angiotensin-converting enzyme
      inhibitor, enalapril. The increased interstitial volume (Vv(int)) in the C57BI/6
      wild-type mouse was decreased in the AT(1a) KO from 32.8 +/- 4.0 to 21.0 +/- 3.7%
      (P < 0.005) or in the TNFR1/TNFR2 KO to 22.3 +/- 2.1% (P < 0.005). The Vv(int) of
      the TNFR1/TNFR2 KO was further decreased to 15.2 +/- 3.7% (P < 0.01) by enalapril
      compared with no treatment. The induction of TNF-alpha mRNA and transforming
      growth factor-beta1 (TGF-beta1) mRNA in the kidney with UUO was significantly
      blunted in the AT(1a) or TNFR1/TNFR2 KO mice compared with the wild-type mice.
      Treatment of the TNFR1/TNFR2 KO mouse with enalapril reduced both TNF-alpha and
      TGF-beta1 mRNA and their proteins to near normal levels. Also, alpha-smooth
      muscle actin expression and myofibroblast proliferation were significantly
      inhibited in the AT(1a) or TNFR1/TNFR2 KO mice, and they were further inhibited
      in enalapril-treated TNFR1/TNFR2 KO mice. Incapacitating the angiotensin II or
      the TNF-alpha systems individually leads to partial blunting of fibrosis.
      Incapacitating both systems, by using a combination of genetic and
      pharmacological means, further inhibited interstitial fibrosis and tubule atrophy
      in obstructive nephropathy.

PMID- 11292621
TI  - Absence of aquaporin-4 water channels from kidneys of the desert rodent Dipodomys
      merriami merriami.
AB  - Recently, we found that aquaporin-4 (AQP4) is expressed in the S3 segment of
      renal proximal tubules of mice but not in rat proximal tubules. Because mice have
      relatively larger papillae than rats, it was proposed that the renal distribution
      of AQP4 in various species could be related to their maximum urinary
      concentrating ability. Therefore, kidneys and other tissues of Merriam's desert
      kangaroo rat, Dipodomys merriami merriami, which produce extremely concentrated
      urine (up to 5,000 mosmol/kgH(2)O), were examined for AQP4 expression and
      localization. Contrary to our expectation, AQP4 immunostaining was undetectable
      in any region of the kidney, and the absence of AQP4 protein was confirmed by
      Western blotting. By freeze fracture electron microscopy, orthogonal arrays of
      intramembraneous particles (OAPs) were not detectable in plasma membranes of
      principal cells and proximal tubules. However, AQP4 protein was readily
      detectable in gastric parietal and brain astroglial cells. Northern blotting
      failed to detect AQP4 mRNA in kangaroo rat kidneys, whereas both in situ
      hybridization and RT-PCR experiments did reveal AQP4 mRNA in collecting ducts and
      proximal tubules of the S3 segment. These results suggest that renal expression
      of AQP4 in the kangaroo rat kidney is regulated at the transcriptional or
      translational level, and the absence of AQP4 may be critical for the extreme
      urinary concentration that occurs in this species.

PMID- 11292622
TI  - Cellular localization of divalent metal transporter DMT-1 in rat kidney.
AB  - We have demonstrated that the kidney plays an important role in iron balance and
      that metabolically significant reabsorption of this ion occurs in the loop of
      Henle and the collecting ducts [Wareing M, Ferguson CJ, Green R, Riccardi D, and
      Smith CP. J Physiol (Lond) 524: 581-586, 2000]. To test the possibility that the
      divalent metal transporter DMT1 (Gunshin H, Mackenzie B, Berger UV, Gunshin Y,
      Romero MF, Boron WF, Nussberger S, Gollan JL, and Hediger MA. Nature 388: 482
      488, 1997) could represent the apical route for iron entry in the kidney, we
      raised and affinity-purified an anti-DMT-1 polyclonal antibody and determined DMT
      1 distribution in rat kidney by Western analysis, immunofluorescence, and
      confocal microscopy. The strongest DMT1-specific (i.e., peptide-protectable)
      immunoreactivity was found in the collecting ducts, in both principal and
      intercalated cells. Thick ascending limbs of Henle's loop and, more intensely,
      distal convoluted tubules exhibited apical immunostaining. Considerable
      intracellular DMT-1 immunoreactivity was seen throughout the nephron,
      particularly in S3 segments. The described distribution of DMT-1 protein is in
      agreement with our previous identification of nephron sites of iron reabsorption,
      suggesting that DMT-1 provides the molecular mechanism for apical iron entry in
      the distal nephron but not in the proximal tubule. Basolateral iron exit may be
      facilitated by a different system.

PMID- 11292623
TI  - The calcium-sensing receptor regulates calcium absorption in MDCK cells by
      inhibition of PMCA.
AB  - Calcium transport across a monolayer of Madin-Darby canine kidney (MDCK) cells
      was measured in response to stimulation of the basal surface with calcium-sensing
      receptor (CaR) agonists. Stimulation of the CaR resulted in a time- and
      concentration-dependent inhibition of calcium transport but did not change
      transepithelial voltage or resistance. Inhibition of transport was not altered by
      pretreatment of cells with pertussis toxin but was blocked by the phospholipase C
      (PLC) inhibitor U-73122. To determine a potential mechanism by which the CaR
      could inhibit calcium transport, we measured activity of the plasma membrane
      calcium ATPase (PMCA). Stimulation of the CaR on the basal surface resulted in an
      inhibition of the PMCA in a concentration- and PLC-dependent manner. Thus
      stimulation of the CaR inhibits both calcium transport and PMCA activity through
      a PLC-dependent pathway. These studies provide the first direct evidence that
      calcium can inhibit its own transcellular absorption in a model of the distal
      tubule. In addition, they provide a potential mechanism for the CaR to inhibit
      calcium transport, inhibition of PMCA.

PMID- 11292624
TI  - Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome.
AB  - Lecithin-cholesterol acetyltransferase (LCAT) is involved in the synthesis of
      plasma cholesteryl esters and is pivotal in the maturation of plasma high-density
      lipoprotein (HDL) and conversion of HDL3 to HDL2. In nephrotic syndrome (NS), the
      ratio of HDL2 to HDL3 is low even though the total concentration of HDL is
      generally normal. We hypothesize that the reduced HDL2/HDL3 ratio in NS is due to
      urinary losses of LCAT, leading to plasma LCAT deficiency. To test this
      hypothesis, Sprague-Dawley rats were randomized to NS (given 130 mg puromycin
      aminonucleoside on day 1 and 60 mg ip on day 14) or control groups and were
      studied on day 30. To dissect the effect of proteinuria from hypoalbuminemia, a
      group of Nagase rats with inherited hypoalbuminemia was included. Hepatic LCAT
      and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA abundance and plasma
      and urine LCAT activity were measured. The NS group showed a fourfold rise in
      serum cholesterol and triglycerides, a fivefold rise in free cholesterol, and a
      fourfold fall in the HDL-to-total cholesterol ratio. Despite severe
      hypoalbuminemia, the Nagase rats showed only a mild elevation of serum
      cholesterol and triglycerides with a normal serum free cholesterol and HDL-to
      total cholesterol ratio. The NS group exhibited a normal hepatic LCAT-to-GAPDH
      mRNA ratio, a marked reduction in plasma LCAT activity, and a significant
      increase in urinary LCAT excretion. LCAT/GAPDH mRNA and plasma and urine LCAT
      were normal in Nagase rats. Thus NS led to heavy urinary losses and reduced
      plasma concentration of LCAT, despite normal hepatic LCAT mRNA abundance.
      However, hypoalbuminemia, per se, without proteinuria as seen in the Nagase rats
      had no effect on plasma LCAT or the HDL-to-total cholesterol ratio. Therefore,
      proteinuria, not hypoalbuminemia, causes LCAT deficiency and a depressed HDL-to
      total cholesterol ratio in NS.

PMID- 11292625
TI  - Effects of P-glycoprotein on cell volume regulation in mouse proximal tubule.
AB  - The role of P-glycoprotein (P-gp) in cell volume regulation was examined in
      isolated nonperfused proximal tubule S2 segments from wild-type (WT) mice and
      those in which both mdr1a and mdr1b genes were knocked out (KO). When the
      osmolality of the bathing solution was rapidly decreased from 300 to 180
      mosmol/kgH(2)O, the tubules from both the WT and KO mice exhibited regulatory
      volume decrease (RVD) by a similar magnitude after the initial cell swelling. The
      peritubular addition of two P-pg inhibitors (verapamil and cyclosporin A) to
      either group of the tubules had no effect on RVD. When the tubules from the WT
      mice were rapidly exposed to a hyperosmotic solution (500 mosmol/kgH(2)O)
      including 200 mM mannitol, they abruptly shrank to 82.1% of their control volume
      but remained in a shrunken state during the experimental period, indicating a
      lack of regulatory volume increase (RVI). The addition of the two P-gp
      inhibitors, but not the inhibitor of the renal organic cation transport system
      (tetraethylammonium), to the tubules from the WT mice resulted in RVI.
      Surprisingly, when the tubules from the KO mice were exposed to the hyperosmotic
      solution, they abruptly shrank to 79.9% of their control volume, and then
      gradually swelled to 87.7% of their control volume, showing RVI. However,
      exposure of the tubules from the KO mice to the hyperosmotic solution in the
      presence of the two P-gp inhibitors had no effect on RVI. When the tubules of the
      WT mice were exposed to the hyperosmotic solution including either of the two P
      gp inhibitors, in the absence of peritubular Na+ or in the presence of
      peritubular ethylisopropylamiloride (EIPA; the specific inhibitor of Na+/H+
      exchange), they did not exhibit RVI. In the tubules of the KO mice, both removing
      peritubular Na+ and adding peritubular EIPA inhibited RVI induced by the
      hyperosmotic solution. We conclude that 1) in mouse proximal tubule, P-gp
      modulates RVI during hyperosmotic stress but not RVD during hyposmotic stress and
      2) basolateral membrane Na+/H+ exchange partly contributes to the P-gp-induced
      modulation of RVI under hyperosmotic stress.

PMID- 11292626
TI  - Endothelial nitric oxide synthase plays an essential role in regulation of renal
      oxygen consumption by NO.
AB  - Nitric oxide (NO) regulates renal O2 consumption, but the source of NO mediating
      this effect is unclear. We explored the effects of renal NO production on O2
      consumption using renal cortex from mice deficient (-/-) in endothelial (e)
      nitric oxide synthase (NOS). O2 consumption was determined polarographically in
      slices of cortex from control and eNOS-/- mice. NO production was stimulated by
      bradykinin (BK) or ramiprilat (Ram) in the presence or absence of an NOS
      inhibitor. Basal O2 consumption was higher in eNOS-/- mice than in heterozygous
      controls (919 +/- 46 vs. 1,211 +/- 133 nmol O(2). min(-1). g(-1); P < 0.05). BK
      and Ram decreased O2 consumption significantly less in eNOS-/- mice [eNOS-/-: BK 
      19.0 +/- 2.8%, Ram -20.5 +/- 3.3% at 10(-4) M; control: BK -29.5 +/- 2.5%, Ram 
      34 +/- 1.6% at 10(-4) M]. The NO synthesis inhibitor nitro-L-arginine methyl
      ester (L-NAME) attenuated this decrease in control but not eNOS-/- mice. An NO
      donor inhibited O2 consumption similarly in both groups independent of the
      presence of L-NAME. These results demonstrate that NO production by eNOS is
      responsible for regulation of renal O2 consumption in mouse kidney.

PMID- 11292627
TI  - SFKs, Ras, and the classic MAPK pathway couple muscarinic receptor activation to
      increased Na-HCO(3) cotransport activity in renal epithelial cells.
AB  - Cholinergic agents are known to affect the epithelial transport of H2O and
      electrolytes in the kidney. In proximal tubule cells, cholinergic agonists
      increase basolateral Na-HCO(3) cotransport activity via M(1) muscarinic receptor
      activation. The signaling intermediates that couple these G protein-coupled
      receptors to cotransporter activation, however, are not well defined. We
      therefore sought to identify distal effectors of muscarinic receptor activation
      that contribute to increased NBC activity in cultured proximal tubule cells. As
      demonstrated previously for acute CO2-regulated cotransport activity, we found
      that inhibitors of Src family kinases (SFKs) or the classic mitogen-activated
      protein kinase (MAPK) pathway prevented the stimulation of NBC activity by
      carbachol. The ability of carbachol to activate Src, as well as the proximal
      (Raf) and distal [extracellular signal-regulated kinases 1 and 2 (ERK1/2)]
      elements of the classic MAPK module, was compatible with these findings.
      Cholinergic stimulation of ERK1/2 activity was also completely prevented by
      overexpression of a dominant negative mutant of Ras (N17-Ras). Taken together,
      these findings suggest a requirement for the sequential activation of SFKs, Ras,
      and the classic MAPK pathway [Raf-->MAPK/ERK kinase (MEK)-->ERK]. These findings
      provide important insights into the molecular mechanisms underlying cholinergic
      regulation of NBC activity in renal epithelial cells. They also suggest a
      specific mechanism whereby cholinergic stimulation of the kidney can contribute
      to pH homeostasis.

PMID- 11292628
TI  - Overexpression of protein kinase G using adenovirus inhibits cyclin E
      transcription and mesangial cell cycle.
AB  - The cGMP-cGMP-dependent protein kinase (protein kinase G) system plays an
      important role in the pathogenesis of mesangial proliferative glomerulonephritis.
      However, the molecular mechanisms of the inhibitory effects of the cGMP-protein
      kinase G system in the cell cycle progression of mesangial cells are not well
      known. To determine the inhibitory pathway of cGMP-protein kinase G in cultured
      mesangial cells, we investigated the effects of cGMP- and adenovirus-mediated
      overexpression of protein kinase G on the promoter activities of cyclin E, cyclin
      D1, and cyclin A. 8-Bromo-cGMP (8-BrcGMP) and overexpression of protein kinase G
      reduced [(3)H]thymidine uptake, reduced the numbers of cells in S and G(2)/M
      phases, and decreased the phosphorylation of retinoblastoma (Rb) protein. 8
      BrcGMP (10(-3) M), protein kinase G adenovirus (Ad-cGKIbeta; 10(10) plaque
      forming units/ml), atrial natriuretic peptide (ANP), and C-type natriuretic
      peptide (CNP) inhibited the promoter activity of cyclin E to 49, 57, 77, and 78%,
      respectively. On the other hand, the promoter activities of cyclin D1 and cyclin
      A were not changed significantly. In Western blot analysis, 8-BrcGMP, Ad
      cGKIbeta, ANP, and CNP also inhibited cyclin E protein expression dose and time
      dependently. The p44/p42 mitogen-activated protein kinase (MAPK) kinase 1-p44/p42
      MAPK had no effect on cyclin E promoter activities, and the cGMP-protein kinase G
      pathway did not change MAPK activity. In conclusion, our findings suggest that
      the reduction of the cyclin E promoter activity that downregulates G(1)/S
      transition plays a dominant role in the cGMP- and protein kinase G-induced
      inhibition of mesangial cell proliferation.

PMID- 11292629
TI  - Effect of water deprivation and hypertonic saline infusion on urinary AQP2
      excretion in healthy humans.
AB  - Arginine vasopressin (AVP) mediates water transport in the renal collecting ducts
      by forming water channels of aquaporin-2 (AQP2) in the apical plasma membrane.
      AQP2 is excreted in human urine. We wanted to test the hypothesis that urinary
      excretion of AQP2 (u-AQP2) reflects the effect of AVP on the renal collecting
      ducts during water deprivation and hypertonic saline infusion in healthy
      subjects. Fifteen healthy subjects underwent a 24-h period of fluid restriction.
      Urine and blood samples were collected at timed intervals. Fifteen healthy
      subjects were given 7 ml/kg 3% hypertonic saline infusion for 30 min. Urine and
      blood samples were collected at timed intervals. During fluid restriction, the u
      AQP2 rate increased from 3.9 (25th percentile: 3.1; 75th percentile: 5.2) to 7.6
      (5.9-9.1; P < 0.001) ng/min, and the plasma AVP (p-AVP) level increased from 0.5
      (0.4-0.6) to 3 (1.7-3.3) pmol/l. There was a positive correlation between the
      maximum change in u-AQP2 rate and the maximum change in p-AVP (r = 0.57, P <
      0.03). During the infusion study, u-AQP2 rate was at maximum 90 min after the
      infusion [baseline: 4.5 ng/min (3.5-4.8); 90 min: 5 ng/min (4.5-6.0) P < 0.02]. p
      AVP increased from 1.0 (0.9-1.1) to 1.5 (1.2-1.8; P < 0.002) pmol/l. There was a
      positive correlation between the maximum change in u-AQP2 rate and the maximum
      change in p-AVP (r = 0.83; P < 0.0001). It can be concluded that p-AVP and u-AQP2
      are increased during thirst and hypertonic saline infusion and that u-AQP2
      reflects the action of AVP on the collecting ducts.

PMID- 11292630
TI  - 1,25(OH)(2)D(3) stimulates Mg2+ uptake into MDCT cells: modulation by
      extracellular Ca2+ and Mg2+.
AB  - The distal convoluted tubule plays a significant role in renal magnesium
      conservation. Although the cells of the distal convoluted tubule possess the
      vitamin D receptor, little is known about the effects of 1alpha,25
      dihydroxyvitamin D [1,25(OH)(2)D(3)] on magnesium transport. In this study, we
      examined the effect of 1,25(OH)(2)D(3) on distal cellular magnesium uptake and
      the modulation of this response by extracellular Ca2+ and Mg2+ in an immortalized
      mouse distal convoluted tubule (MDCT) cell line. MDCT cells possess the divalent
      cation-sensing receptor (CaSR) that responds to elevation of extracellular Ca2+
      and Mg2+ concentrations to diminish peptide hormone-stimulated Mg2+ uptake. Mg2+
      uptake rates were determined by microfluorescence in Mg2+ -depleted MDCT cells.
      Treatment of MDCT cells with 1,25(OH)(2)D(3) for 16-24 h stimulated basal Mg2+
      uptake in a concentration-dependent manner from basal levels of 164 +/- 5 to 210
      +/- 11 nM/s, representing a 28 +/- 3% change. Pretreatment with actinomycin D or
      cycloheximide abolished 1,25(OH)(2)D(3)-stimulated(.)Mg2+ uptake (154 +/- 18
      nM/s), suggesting that 1,25(OH)(2)D(3) stimulates Mg2+ uptake through gene
      activation and protein synthesis. Elevation of extracellular Ca2+ inhibited
      1,25(OH)(2)D(3)-stimulated Mg2+ uptake (143 +/- 5 nM/s). Preincubation of the
      cells with an antibody to the CaSR prevented the inhibition by elevated
      extracellular Ca2+ of 1,25(OH)(2)D(3)-stimulated Mg2+ uptake (202 +/- 8 nM/s).
      Treatment with an antisense CaSR mRNA oligodeoxynucleotide also abolished the
      effects of extracellular Ca2+ on 1,25(OH)(2)D(3)-responsive Mg2+ entry. This
      showed that elevated extracellular calcium modulates 1,25(OH)(2)D-mediated
      responses through the CaSR. In summary, 1,25(OH)(2)D(3) stimulated Mg2+ uptake in
      MDCT cells, and this is dependent on de novo protein synthesis. Elevation of
      extracellular Ca2+, acting via the CaSR, inhibited 1,25(OH)(2)D(3)-stimulated
      Mg2+ entry. These data indicate that 1,25(OH)(2)D(3) has important effects on the
      control of magnesium entry in MDCT cells and these responses can be modulated by
      extracellular divalent cations.

PMID- 11292631
TI  - Localization of GFP-tagged concentrative nucleoside transporters in a renal
      polarized epithelial cell line.
AB  - Many nucleosides undergo active reabsorption within the kidney, probably via
      nucleoside transporters. To date, two concentrative nucleoside transporters have
      been cloned, the sodium-dependent purine-selective nucleoside transporter (SPNT)
      and concentrative nucleoside transporter 1 (CNT1). We report the stable
      expression of green fluorescence protein (GFP)-tagged SPNT and CNT1 in Madin
      Darby canine kidney (MDCK) cells, a polarized renal epithelial line. We
      demonstrate that the GFP tag does not alter the substrate selectivity and only
      modestly affects the kinetic activity of the transporters. By using confocal
      microscopy and functional studies, both SPNT and CNT1 are localized primarily to
      the apical membrane of MDCK and LLC-PK(1) cells. Apical localization of these
      transporters suggests a role in renal nucleoside reabsorption and regulation of
      tubular function via the adenosine pathway.

PMID- 11292632
TI  - Ischemic injury induces ADF relocalization to the apical domain of rat proximal
      tubule cells.
AB  - Breakdown of proximal tubule cell apical membrane microvilli is an early
      occurring hallmark of ischemic acute renal failure. Intracellular mechanisms
      responsible for these apical membrane changes remain unknown, but it is known
      that actin cytoskeleton alterations play a critical role in this cellular
      process. Our laboratory previously demonstrated that ischemia-induced cell injury
      resulted in dephosphorylation and activation of the actin-binding protein, actin
      depolymerizing factor [(ADF); Schwartz, N, Hosford M, Sandoval RM, Wagner MC,
      Atkinson SJ, Bamburg J, and Molitoris BA. Am J Physiol Renal Fluid Electrolyte
      Physiol 276: F544-F551, 1999]. Therefore, we postulated that ischemia-induced ADF
      relocalization from the cytoplasm to the apical microvillar microfilament core
      was an early event occurring before F-actin alterations. To directly investigate
      this hypothesis, we examined the intracellular localization of ADF in ischemic
      rat cortical tissues by immunofluorescence and quantified the concentration of
      ADF in brush-border membrane vesicles prepared from ischemic rat kidneys by using
      Western blot techniques. Within 5 min of the induction of ischemia, ADF
      relocalized to the apical membrane region. The length of ischemia correlated with
      the time-related increase in ADF in isolated brush-border membrane vesicles.
      Finally, depolymerization of microvillar F-actin to G-actin was documented by
      using colocalization studies for G- and F-actin. Collectively, these data
      indicate that ischemia induces ADF activation and relocalization to the apical
      domain before microvillar destruction. These data further suggest that ADF plays
      a critical role in microvillar microfilament destruction and apical membrane
      damage during ischemia.

PMID- 11292633
TI  - Maturation of carbonic anhydrase IV expression in rabbit kidney.
AB  - Carbonic anhydrase (CA) IV facilitates renal acidification by catalyzing the
      dehydration of luminal H(2)CO(3). CA IV is expressed in proximal tubules,
      medullary collecting ducts, and A-intercalated cells of the mature rabbit kidney
      (Schwartz GJ, Kittelberger AM, Barnhart DA, and Vijayakumar S. Am J Physiol 278:
      F894-F904, 2000). In view of the maturation of HCO transport in the proximal
      tubule and collecting duct, the ontogeny of CA IV expression was examined. During
      the first 2 wk, CA IV mRNA was expressed in maturing cortex and medulla at ~20%
      of adult levels. The maturational increase was gradual in cortex over 3-5 wk of
      age but surged in the medulla, so that mRNA levels appeared higher than those in
      the adult medulla. In situ hybridization showed very little CA IV mRNA at 5 days,
      with increases in deep cortex and medullary collecting ducts by 21 days.
      Expression of CA IV protein in the cortex and medulla was minimal at 3 days of
      age but then apparent in the juxtamedullary region, A-intercalated cells and
      medullary collecting ducts by 18 days; there was little labeling of the proximal
      straight tubules of the medullary rays. Thus CA IV expression may be regulated to
      accommodate the maturational increase in HCO absorption in the proximal tubule.
      In the medullary collecting duct, there is a more robust maturation of CA IV mRNA
      and protein, commensurate with the high rate of HCO absorption in the neonatal
      segment.

PMID- 11292634
TI  - Urea inhibits hypertonicity-inducible TonEBP expression and action.
AB  - Tonicity-responsive genes are regulated by the TonE enhancer element and the
      tonicity-responsive enhancer binding protein (TonEBP) transcription factor with
      which it interacts. Urea, a permeant solute coexistent with hypertonic NaCl in
      the mammalian renal medulla, activates a characteristic set of signaling events
      that may serve to counteract the effects of NaCl in some contexts. Urea inhibited
      the ability of hypertonic stressors to increase expression of TonEBP mRNA and
      also inhibited tonicity-inducible TonE-dependent reporter gene activity. The
      permeant solute glycerol failed to reproduce these effects, as did cell
      activators including peptide mitogens and phorbol ester. The inhibitory effect of
      urea was evident as late as 2 h after the application of hypertonicity.
      Pharmacological inhibitors of known urea-inducible signaling pathways failed to
      abolish the inhibitory effect of urea. TonEBP action is incompletely understood,
      but evidence supports a role for proteasome function and p38 action in
      regulation; urea failed to inhibit proteasome function or p38 signaling in
      response to hypertonicity. Consistent with its effect on TonEBP expression and
      action, urea pretreatment inhibited the effect of hypertonicity on expression of
      the physiological effector gene, aldose reductase. Taken together, these data 1)
      define a molecular mechanism of urea-mediated inhibition of tonicity-dependent
      signaling, and 2) underscore a role for TonEBP abundance in regulating TonE
      mediated gene transcription.

PMID- 11292635
TI  - Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD.
AB  - In rat kidney the "secretory" isoform of the Na+-K+-2Cl- cotransporter (NKCC1)
      localizes to the basolateral membrane of the alpha-intercalated cell. The purpose
      of this study was to determine whether rat outer medullary collecting duct (OMCD)
      secretes Cl- and whether transepithelial Cl- transport occurs, in part, through
      Cl- uptake across the basolateral membrane mediated by NKCC1 in series with Cl-
      efflux across the apical membrane. OMCD tubules from rats treated with
      deoxycorticosterone pivalate were perfused in vitro in symmetrical HCO/CO2
      buffered solutions. Cl- secretion was observed in this segment, accompanied by a
      lumen positive transepithelial potential. Bumetanide (100 microM), when added to
      the bath, reduced Cl- secretion by 78%, although the lumen positive
      transepithelial potential and fluid flux were unchanged. Bumetanide-sensitive Cl-
      secretion was dependent on extracellular Na+ and either K+ or NH, consistent with
      the ion dependency of NKCC1-mediated Cl- transport. In conclusion, OMCD tubules
      from deoxycorticosterone pivalate-treated rats secrete Cl- into the luminal fluid
      through NKCC1-mediated Cl- uptake across the basolateral membrane in series with
      Cl- efflux across the apical membrane. The physiological role of NKCC1-mediated
      Cl- uptake remains to be determined. However, the role of NKCC1 in the process of
      fluid secretion could not be demonstrated.

PMID- 11292636
TI  - Regulation of proximal tubule sodium/hydrogen antiporter with chronic volume
      contraction.
AB  - We developed a model of volume contraction in rabbits by using a furosemide/low
      salt diet to follow changes, if any, in proximal tubule Na+/H+ exchanger 3 (NHE3)
      mRNA and brush-border protein. The rabbits' plasma renin, aldosterone, and urine
      sodium content confirmed the volume-contracted state. RNase protection assays
      demonstrated increases in treated-animal NHE3 mRNA as a percentage of control
      with 172 +/- 23, 154 +/- 15, 153 +/- 14, and 141 +/- 7 (SE) % (P < 0.05) at 1, 5,
      10, and 31 days, respectively. Western analysis of brush-border membrane with
      NHE3 antibody revealed increased immunoreactivity in treated animals as a
      percentage of control with 120 +/- 30, 190 +/- 59, 307 +/- 72, and 427 +/- 41% (P
      < 0.05) at 1, 5, 10, and 31 days, respectively. There was no significant
      difference in serum potassium, bicarbonate, and cortisol in control vs.
      experimental animals. These data suggest that there is chronic upregulation of
      NHE3 in the volume-contracted state.

PMID- 11292637
TI  - Leishmaniasis: current status of vaccine development.
AB  - Leishmaniae are obligatory intracellular protozoa in mononuclear phagocytes. They
      cause a spectrum of diseases, ranging in severity from spontaneously healing skin
      lesions to fatal visceral disease. Worldwide, there are 2 million new cases each
      year and 1/10 of the world's population is at risk of infection. To date, there
      are no vaccines against leishmaniasis and control measures rely on chemotherapy
      to alleviate disease and on vector control to reduce transmission. However, a
      major vaccine development program aimed initially at cutaneous leishmaniasis is
      under way. Studies in animal models and humans are evaluating the potential of
      genetically modified live attenuated vaccines, as well as a variety of
      recombinant antigens or the DNA encoding them. The program also focuses on new
      adjuvants, including cytokines, and delivery systems to target the T helper type
      1 immune responses required for the elimination of this intracellular organism.
      The availability, in the near future, of the DNA sequences of the human and
      Leishmania genomes will extend the vaccine program. New vaccine candidates such
      as parasite virulence factors will be identified. Host susceptibility genes will
      be mapped to allow the vaccine to be targeted to the population most in need of
      protection.

PMID- 11292638
TI  - Wound microbiology and associated approaches to wound management.
AB  - The majority of dermal wounds are colonized with aerobic and anaerobic
      microorganisms that originate predominantly from mucosal surfaces such as those
      of the oral cavity and gut. The role and significance of microorganisms in wound
      healing has been debated for many years. While some experts consider the
      microbial density to be critical in predicting wound healing and infection,
      others consider the types of microorganisms to be of greater importance. However,
      these and other factors such as microbial synergy, the host immune response, and
      the quality of tissue must be considered collectively in assessing the
      probability of infection. Debate also exists regarding the value of wound
      sampling, the types of wounds that should be sampled, and the sampling technique
      required to generate the most meaningful data. In the laboratory, consideration
      must be given to the relevance of culturing polymicrobial specimens, the value in
      identifying one or more microorganisms, and the microorganisms that should be
      assayed for antibiotic susceptibility. Although appropriate systemic antibiotics
      are essential for the treatment of deteriorating, clinically infected wounds,
      debate exists regarding the relevance and use of antibiotics (systemic or
      topical) and antiseptics (topical) in the treatment of nonhealing wounds that
      have no clinical signs of infection. In providing a detailed analysis of wound
      microbiology, together with current opinion and controversies regarding wound
      assessment and treatment, this review has attempted to capture and address
      microbiological aspects that are critical to the successful management of
      microorganisms in wounds.

PMID- 11292639
TI  - Schistosomiasis in the People's Republic of China: prospects and challenges for
      the 21st century.
AB  - Schistosomiasis japonica is a serious communicable disease and a major disease
      risk for more than 30 million people living in the tropical and subtropical zones
      of China. Infection remains a major public health concern despite 45 years of
      intensive control efforts. It is estimated that 865,000 people and 100,250
      bovines are today infected in the provinces where the disease is endemic, and its
      transmission continues. Unlike the other schistosome species known to infect
      humans, the oriental schistosome, Schistosoma japonicum, is a true zoonotic
      organism, with a range of mammalian reservoirs, making control efforts extremely
      difficult. Clinical features of schistosomiasis range from fever, headache, and
      lethargy to severe fibro-obstructive pathology leading to portal hypertension,
      ascites, and hepatosplenomegaly, which can cause premature death. Infected
      children are stunted and have cognitive defects impairing memory and learning
      ability. Current control programs are heavily based on community chemotherapy
      with a single dose of the drug praziquantel, but vaccines (for use in bovines and
      humans) in combination with other control strategies are needed to make
      elimination of the disease possible. In this article, we provide an overview of
      the biology, epidemiology, clinical features, and prospects for control of
      oriental schistosomiasis in the People's Republic of China.

PMID- 11292641
TI  - Global impact of human immunodeficiency virus and AIDS.
AB  - This review provides information on the epidemiology, economic impact, and
      intervention strategies for the human immunodeficiency virus (HIV)/AIDS pandemic
      in developing countries. According to the World Health Organization and the Joint
      United Nations Programme on HIV/AIDS (UNAIDS) at the end of 1999, an estimated
      34.3 million people were living with HIV/AIDS. Most of the people living with
      HIV, 95% of the global total, live in developing countries. Examples of the
      impact of HIV/AIDS in Africa, Asia, Latin America, the Caribbean, and the Newly
      Independent States provide insight into the demographics, modes of exposure,
      treatment and prevention options, and the economic effect of the epidemic on the
      global community. The epidemic in each region of the world is influenced by the
      specific risk factors that are associated with the spread of HIV/AIDS and the
      responses that have evolved to address it. These influences are important in
      developing HIV/AIDS policies and programs to effectively address the global
      pandemic.

PMID- 11292643
TI  - Bioterrorism: implications for the clinical microbiologist.
AB  - The specter of bioterrorism has captured the attention of government and military
      officials, scientists, and the general public. Compared to other sectors of the
      population, clinical microbiologists are more directly impacted by concerns about
      bioterrorism. This review focuses on the role envisioned for clinical
      laboratories in response to a bioterrorist event. The microbiology and clinical
      aspects of the biological agents thought to be the most likely tools of
      bioterrorists are presented. The historical background of the problem of
      bioterrorism and an overview of current U.S. preparedness planning, with an
      emphasis on the roles of health care professionals, are also included.

PMID- 11292644
TI  - Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus
      infections.
AB  - Poxviruses continue to pose a major threat to human health. Monkeypox is endemic
      in central Africa, and the discontinuation of the vaccination (with vaccinia
      virus) has rendered most humans vulnerable to variola virus, the etiologic agent
      of smallpox, should this virus be used in biological warfare or terrorism.
      However, a large variety of compounds have been described that are potent
      inhibitors of vaccinia virus replication and could be expected to be active
      against other poxviruses as well. These compounds could be grouped in different
      classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase
      inhibitors (e.g., 5'-noraristeromycin, 3-deazaneplanocin A, and various
      neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin)
      and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate
      synthase inhibitors (e.g., 5-substituted 2'-deoxyuridines); (v) nucleoside
      analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic
      nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii)
      polyanionic substances (e.g., polyacrylic acid). All these compounds could be
      considered potential candidate drugs for the therapy and prophylaxis of poxvirus
      infections at large. Some of these compounds, in particular polyacrylic acid and
      cidofovir, were found to generate, on single-dose administration, a long-lasting
      protective efficacy against vaccinia virus infection in vivo. Cidofovir, which
      has been approved for the treatment of cytomegalovirus retinitis in
      immunocompromised patients, was also found to protect mice, again when given as a
      single dose, against a lethal aerosolized or intranasal cowpox virus challenge.
      In a biological warfare scenario, it would be advantageous to be able to use a
      single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir
      thus holds great promise for treating human smallpox, monkeypox, and other
      poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in
      the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma
      contagiosum) in immunosuppressed patients.

PMID- 11292642
TI  - Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of
      the-art review.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
      in the United States. The precise role of bacterial infection in the course and
      pathogenesis of COPD has been a source of controversy for decades. Chronic
      bacterial colonization of the lower airways contributes to airway inflammation;
      more research is needed to test the hypothesis that this bacterial colonization
      accelerates the progressive decline in lung function seen in COPD (the vicious
      circle hypothesis). The course of COPD is characterized by intermittent
      exacerbations of the disease. Studies of samples obtained by bronchoscopy with
      the protected specimen brush, analysis of the human immune response with
      appropriate immunoassays, and antibiotic trials reveal that approximately half of
      exacerbations are caused by bacteria. Nontypeable Haemophilus influenzae,
      Moraxella catarrhalis, and Streptococcus pneumoniae are the most common causes of
      exacerbations, while Chlamydia pneumoniae causes a small proportion. The role of
      Haemophilus parainfluenzae and gram-negative bacilli remains to be established.
      Recent progress in studies of the molecular mechanisms of pathogenesis of
      infection in the human respiratory tract and in vaccine development guided by
      such studies promises to lead to novel ways to treat and prevent bacterial
      infections in COPD.

PMID- 11292647
TI  - Apoptosis in sepsis: a new target for therapeutic exploration.
AB  - The treatment of sepsis and septic shock remains a clinical conundrum, and recent
      prospective trials with biological response modifiers aimed at the inflammatory
      response have shown only modest clinical benefit. Recently, interest has shifted
      toward therapies aimed at reversing the accompanying periods of immune
      suppression. Studies in experimental animals and critically ill patients have
      demonstrated that increased apoptosis of lymphoid organs and some parenchymal
      tissues contributes to this immune suppression, anergy, and organ system
      dysfunction. During sepsis syndromes, lymphocyte apoptosis can be triggered by
      the absence of IL-2 or by the release of glucocorticoids, granzymes, or the so
      called 'death' cytokines: tumor necrosis factor alpha or Fas ligand. Apoptosis
      proceeds via auto-activation of cytosolic and/or mitochondrial caspases, which
      can be influenced by the pro- and anti-apoptotic members of the Bcl-2 family. In
      experimental animals, not only can treatment with inhibitors of apoptosis prevent
      lymphoid cell apoptosis; it may also improve outcome. Although clinical trials
      with anti-apoptotic agents remain distant due in large part to technical
      difficulties associated with their administration and tissue targeting,
      inhibition of lymphocyte apoptosis represents an attractive therapeutic target
      for the septic patient.

PMID- 11292648
TI  - Are genetically modified mice useful for the understanding of acute pancreatitis?
AB  - Treatment of patients with acute pancreatitis has greatly improved due to a
      better understanding of the pathophysiology of the disease. This pathophysiology
      includes the activation and release of pancreatic enzymes in the interstitium,
      the autodigestion of the pancreas, and a multiple organ dysfunction after their
      release into the systemic circulation. Moreover, significant evidence exists that
      synthesis and release of proinflammatory cytokines and chemokines are also
      responsible for the local injury and systemic dispersion of the inflammation. The
      use of knockout mice devoid of active pro- or anti-inflammatory mediators allows
      examination of the effects of a specific cytokine without any drawbacks induced
      by pharmacological manipulations. The results obtained from these genetically
      modified mice show that numerous mediators have a major role in the
      pathophysiology of acute pancreatitis. They also clearly demonstrate that a
      single genetic deletion cannot completely prevent the occurrence of pancreatic or
      distant organ injury. However, the fact that the immune system is characterized
      by redundancies of ligands and receptors complicates the full understanding of
      each report. The utility of such experimental models might have limitations, and
      a full extrapolation of experimental data from genetically modified mice to
      humans must be done with caution.

PMID- 11292646
TI  - Vaccination strategies for mucosal immune responses.
AB  - Mucosal administration of vaccines is an important approach to the induction of
      appropriate immune responses to microbial and other environmental antigens in
      systemic sites and peripheral blood as well as in most external mucosal surfaces.
      The development of specific antibody- or T-cell-mediated immunologic responses
      and the induction of mucosally induced systemic immunologic hyporesponsiveness
      (oral or mucosal tolerance) depend on complex sets of immunologic events,
      including the nature of the antigenic stimulation of specialized lymphoid
      structures in the host, antigen-induced activation of different populations of
      regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and
      immunoregulatory cytokines. Availability of mucosal vaccines will provide a
      painless approach to deliver large numbers of vaccine antigens for human
      immunization. Currently, an average infant will receive 20 to 25 percutaneous
      injections for vaccination against different childhood infections by 18 months of
      age. It should be possible to develop for human use effective, nonliving,
      recombinant, replicating, transgenic, and microbial vector- or plant-based
      mucosal vaccines to prevent infections. Based on the experience with many dietary
      antigens, it is also possible to manipulate the mucosal immune system to induce
      systemic tolerance against environmental, dietary, and possibly other
      autoantigens associated with allergic and autoimmune disorders. Mucosal immunity
      offers new strategies to induce protective immune responses against a variety of
      infectious agents. Such immunization may also provide new prophylactic or
      therapeutic avenues in the control of autoimmune diseases in humans.

PMID- 11292645
TI  - Experimental oral candidiasis in animal models.
AB  - Oral candidiasis is as much the final outcome of the vulnerability of the host as
      of the virulence of the invading organism. We review here the extensive
      literature on animal experiments mainly appertaining to the host predisposing
      factors that initiate and perpetuate these infections. The monkey, rat, and mouse
      are the choice models for investigating oral candidiasis, but comparisons between
      the same or different models appear difficult, because of variables such as the
      study design, the number of animals used, their diet, the differences in Candida
      strains, and the duration of the studies. These variables notwithstanding, the
      following could be concluded. (i) The primate model is ideal for investigating
      Candida-associated denture stomatitis since both erythematous and
      pseudomembranous lesions have been produced in monkeys with prosthetic plates;
      they are, however, expensive and difficult to obtain and maintain. (ii) The rat
      model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral
      candidal colonization and infection, due to the ease of breeding and handling and
      their ready availability. (iii) Mice are similar, but in addition there are well
      characterized variants simulating immunologic and genetic abnormalities (e.g.,
      athymic, euthymic, murine-acquired immune deficiency syndrome, and severe
      combined immunodeficient models) and hence are used for short-term studies
      relating the host immune response and oral candidiasis. Nonetheless, an ideal,
      relatively inexpensive model representative of the human oral environment in
      ecological and microbiological terms is yet to be described. Until such a model
      is developed, researchers should pay attention to standardization of the
      experimental protocols described here to obtain broadly comparable and meaningful
      data.

PMID- 11292649
TI  - Keratinocyte growth factor induces hyperproliferation and delays differentiation
      in a skin equivalent model system.
AB  - Keratinocyte growth factor (KGF) is a paracrine mediator of epithelial cell
      growth. To examine the direct effects of KGF on the morphogenesis of the
      epidermis, we generated skin equivalents in vitro by seeding human keratinocytes
      on the papillary surface of acellular dermis and raising them up to the air
      liquid interface. KGF was either added exogenously or expressed by keratinocytes
      via a recombinant retrovirus encoding KGF. KGF induced dramatic changes to the 3
      dimensional organization of the epidermis including pronounced hyperthickening,
      crowding, and elongation of the basal cells, flattening of the rete ridges, and a
      ripple-like pattern in the junction of stratum corneum and granular layers.
      Quantitative immunostaining for the proliferation antigen, Ki67, revealed that in
      addition to increasing basal proliferation, KGF extended the proliferative
      compartment by inducing suprabasal cell proliferation. KGF also induced
      expression of the integrin alpha 5 beta 1 and delayed expression of keratin 10
      and transglutaminase. However, barrier formation of the epidermis was not
      disrupted. These results demonstrate for the first time that a single growth
      factor can alter the 3-dimensional organization and proliferative function of an
      in vitro epidermis. In addition to new strategies for tissue engineering, such a
      well-defined system will be useful for analyzing growth factor effects on the
      complex links between cell proliferation, cell movement and differentiation
      within a stratified tissue.

PMID- 11292640
TI  - Leptospirosis.
AB  - Leptospirosis is a worldwide zoonotic infection with a much greater incidence in
      tropical regions and has now been identified as one of the emerging infectious
      diseases. The epidemiology of leptospirosis has been modified by changes in
      animal husbandry, climate, and human behavior. Resurgent interest in
      leptospirosis has resulted from large outbreaks that have received significant
      publicity. The development of simpler, rapid assays for diagnosis has been based
      largely on the recognition that early initiation of antibiotic therapy is
      important in acute disease but also on the need for assays which can be used more
      widely. In this review, the complex taxonomy of leptospires, previously based on
      serology and recently modified by a genotypic classification, is discussed, and
      the clinical and epidemiological value of molecular diagnosis and typing is also
      evaluated.

PMID- 11292650
TI  - Estrogen augments glucose transporter and IGF1 expression in primate cerebral
      cortex.
AB  - Estrogen has many positive effects on neural tissue in experimental model
      systems, including stimulation of neurite growth and neurotransmitter synthesis
      and protection against diverse types of neural injury. In humans, estrogen
      treatment is reputed to protect against Alzheimer's disease. To investigate
      potential mediators of estrogen's action and determine whether selective estrogen
      receptor modulators (SERMs) such as tamoxifen have estrogen-like effects in the
      primate brain, we evaluated the expression of glucose transporters and insulin
      like growth factor 1 (IGF1) and its receptor in the frontal cortex of
      ovariectomized rhesus monkeys. We treated one group for 3 days with vehicle,
      another with 17 beta estradiol (E2), and a third with tamoxifen. The expression
      of facilitative glucose transporters (Gluts) 1, 3, and 4 was investigated using
      in situ hybridization, immunohistochemistry, and immunoblot analysis. Gluts 3 and
      4 were concentrated in cortical neurons and Glut1 in capillaries and glial cells.
      E2 treatment induced two- to fourfold increases in Glut3 and Glut4 mRNA levels
      and lesser but significant increases in Glut3 and 4 protein levels. E2 treatment
      induced an approximately 70% increase in parenchymal Glut1 mRNA levels, but did
      not appreciably affect vascular Glut1 gene expression. IGF1 and IGF1 receptor
      mRNAs were concentrated in cortical neurons in a distribution similar to Gluts 3
      and 4. IGF1 mRNA levels were significantly increased in E2-treated animals but
      IGF1 receptor mRNA levels were not altered by hormone treatment. Tamoxifen
      increased cerebral cortical Glut3 and 4 mRNA levels, but did not affect Glut1,
      IGF1, or IGF1 receptor expression. This study provides novel data showing that
      Gluts 3 and 4 and IGF1 are coexpressed by primate cerebral cortical neurons,
      where their expression is enhanced by estrogen. These findings suggest that up
      regulation of glucose transporter and IGF1 expression may contribute to
      estrogen's salutary effects on neural tissue. Tamoxifen, an antiestrogen at the
      breast, is shown to have estrogen-like effects on higher brain centers in the
      monkey, suggesting that some SERMs may share estrogen's neuroprotective potential
      for menopausal women.

PMID- 11292651
TI  - Direct binding and functional coupling of alpha-synuclein to the dopamine
      transporters accelerate dopamine-induced apoptosis.
AB  - Mutations in alpha-synuclein, a protein highly enriched in presynaptic terminals,
      have been implicated in the expression of familial forms of Parkinson's disease
      (PD) whereas native alpha-synuclein is a major component of intraneuronal
      inclusion bodies characteristic of PD and other neurodegenerative disorders.
      Although overexpression of human alpha-synuclein induces dopaminergic nerve
      terminal degeneration, the molecular mechanism by which alpha-synuclein
      contributes to the degeneration of these pathways remains enigmatic. We report
      here that alpha-synuclein complexes with the presynaptic human dopamine
      transporter (hDAT) in both neurons and cotransfected cells through the direct
      binding of the non-A beta amyloid component of alpha-synuclein to the carboxyl
      terminal tail of the hDAT. alpha-Synuclein--hDAT complex formation facilitates
      the membrane clustering of the DAT, thereby accelerating cellular dopamine uptake
      and dopamine-induced cellular apoptosis. Since the selective vulnerability of
      dopaminergic neurons in PD has been ascribed in part to oxidative stress as a
      result of the cellular overaccumulation of dopamine or dopamine-like molecules by
      the presynaptic DAT, these data provide mechanistic insight into the mode by
      which the activity of these two proteins may give rise to this process.

PMID- 11292652
TI  - A src-like kinase activates outwardly rectifying chloride channels in CFTR
      defective lymphocytes.
AB  - Defective activation of chloride channels is a hallmark of cystic fibrosis (CF).
      Recently we have described activation of a volume-sensitive, outwardly rectifying
      chloride conductance (I(OR)) through the src-like tyrosine kinase p56(lck). Here
      we show that p56(lck) activates I(OR) independently of CFTR. In lymphocytes from
      healthy donors, chloride channels could be opened by either intracellular cAMP,
      p56(lck) or osmotic swelling. In CF lymphocytes, p56(lck) and cell swelling but
      not cAMP could activate chloride channels. Regulation of I(OR) by p56(lck) thus
      represents an alternative pathway of stimulating membrane chloride conductance
      that is left intact in cystic fibrosis.

PMID- 11292653
TI  - Tumor cell invasion of model 3-dimensional matrices: demonstration of migratory
      pathways, collagen disruption, and intercellular cooperation.
AB  - We report a novel 3-dimensional model for visualizing tumor cell migration across
      a nylon mesh-supported gelatin matrix. To visualize migration across these model
      barriers, cell proteolytic activity of the pericellular matrix was detected using
      Bodipy-BSA (fluorescent upon proteolysis) and DQ collagen (fluorescent upon
      collagenase activity). For 3-dimensional image reconstruction, multiple optical
      images at sequential z axis positions were deconvoluted by computer analysis.
      Specificity was indicated using well-known inhibitors. Using these fluorescent
      proteolysis markers and imaging methods, we have directly demonstrated
      proteolytic and collagenolytic activity during tumor cell invasion. Moreover, it
      is possible to visualize migratory pathways followed by tumor cells during matrix
      invasion. Using cells of differing invasive potentials (uPAR-negative T-47D wild
      type and uPAR-positive T-47D A2--1 cells), we show that the presence of the T-47D
      A2--1 cells facilitates the entry of T-47D wild-type cells into the matrix. In
      some cases, wild-type cells follow T-47D A2--1 cells into the matrix whereas
      other T-47D-wild-type cells appear to enter without the direct intervention of T
      47D A2--1 cells. Thus, we have developed a new 3-dimensional model of tumor cell
      invasion, demonstrated protein and collagen disruption, mapped the pathways
      followed by tumor cells during migration through an extracellular matrix, and
      illustrated cross-talk among tumor cell populations during invasion.

PMID- 11292654
TI  - Human neutrophils express the high-affinity receptor for immunoglobulin E (Fc
      epsilon RI): role in asthma.
AB  - Polymorphonuclear neutrophils (PMNs) are important effector cells in host defense
      and the inflammatory response to antigen. The involvement of PMNs in inflammation
      is mediated mainly by the Fc receptor family, including IgE receptors. Recently,
      PMNs were shown to express two IgE receptors (CD23/Fc epsilon RII and galectin
      3). In allergic diseases, the dominant role of IgE has been mainly ascribed to
      its high-affinity receptor, Fc epsilon RI. We have examined the expression of Fc
      epsilon RI by PMNS: mRNA and cell surface expression of Fc epsilon RI alpha chain
      was identified on PMNs from asthmatic subjects. Furthermore, preincubation with
      human IgE Fc fragment blocks completely the binding of anti-Fc epsilon RI alpha
      chain (mAb15--1) to human PMNS: Conversely, preincubation of PMNs with mAb15--1
      inhibits significantly the binding of IgE Fc fragment to PMNs, indicating that
      IgE bound to the cell surface of PMNs mainly via the Fc epsilon RI. Peripheral
      blood and bronchoalveolar lavage (BAL) PMNs from asthmatic subjects also express
      intracellular Fc epsilon RI alpha and beta chain immunoreactivity. Engagement of
      Fc epsilon RI induces the release of IL-8 by PMNS: Collectively, these
      observations provide new evidence that PMNs express the Fc epsilon RI and suggest
      that these cells may play a role in allergic inflammation through an IgE
      dependent activation mechanism.

PMID- 11292655
TI  - Interleukin 12 and antigen independently induce substance P receptor expression
      in T cells in murine schistosomiasis mansoni.
AB  - Substance P (SP) regulates interferon-gamma (IFN-gamma) production through
      interaction with the SP receptor NK1 (SPr) on T cells at sites of inflammation.
      Using murine schistosomiasis, we evaluated whether SPr expression was subject to
      immunoregulation. Splenocytes from schistosome-infected mice cultured for < or
      =18 h did not express SPr, as determined by quantitative polymerase chain
      reaction assay. However, exposure to schistosome egg antigen (SEA) for < or =4 h
      induced strong receptor expression. Experiments using splenocytes fractionated
      with antibody-coupled, paramagnetic beads showed that induction localized
      exclusively to T cells. Receptor protein expression was confirmed with Western
      blot. Interleukin 12 (IL-12) also induced strong T-cell SPr expression. Both SEA
      and IL-12 remained strong inducers of T-cell SPr in lymphocytes from the IL-12
      (p40) and IFN-gamma R double-knockout mouse, which suggested that SEA did not
      require IL-12 to induce SPr and that both worked independently of IFN-gamma.
      Splenocytes from wild-type mice cultured with SEA and neutralizing anti-IL-12
      monoclonal antibody (mAb) also showed SPr induction. However, anti-Ia mAb
      inhibited SEA induction of SPR: Thus, SPr is inducible on T cells. SEA induces
      SPr through interaction with T-cell receptor (TCR), independently of IL-12 and
      IFN-gamma. IL-12 induces SPr independently of TCR activation and IFN-gamma
      expression. SP and its receptor, which regulate IFN-gamma production, are
      probably part of the IL-12-Th1 circuit.

PMID- 11292656
TI  - Metabolic adaptations in skeletal muscle overexpressing GLUT4: effects on muscle
      and physical activity.
AB  - To understand the long-term metabolic and functional consequences of increased
      GLUT4 content, intracellular substrate utilization was investigated in isolated
      muscles of transgenic mice overexpressing GLUT4 selectively in fast-twitch
      skeletal muscles. Rates of glycolysis, glycogen synthesis, glucose oxidation, and
      free fatty acid (FFA) oxidation as well as glycogen content were assessed in
      isolated EDL (fast-twitch) and soleus (slow-twitch) muscles from female and male
      MLC-GLUT4 transgenic and control mice. In male MLC-GLUT4 EDL, increased glucose
      influx predominantly led to increased glycolysis. In contrast, in female MLC
      GLUT4 EDL increased glycogen synthesis was observed. In both sexes, GLUT4
      overexpression resulted in decreased exogenous FFA oxidation rates. The decreased
      rate of FFA oxidation in male MLC-GLUT4 EDL was associated with increased lipid
      content in liver, but not in muscle or at the whole body level. To determine how
      changes in substrate metabolism and insulin action may influence energy balance
      in an environment that encouraged physical activity, we measured voluntary
      training activity, body weight, and food consumption of MLC-GLUT4 and control
      mice in cages equipped with training wheels. We observed a small decrease in body
      weight of MLC-GLUT4 mice that was paradoxically accompanied by a 45% increase in
      food consumption. The results were explained by a marked fourfold increase in
      voluntary wheel exercise. The changes in substrate metabolism and physical
      activity in MLC-GLUT4 mice were not associated with dramatic changes in skeletal
      muscle morphology. Collectively, results of this study demonstrate the
      feasibility of altering muscle substrate utilization by overexpression of GLUT4.
      The results also suggest that as a potential treatment for type II diabetes
      mellitus, increased skeletal muscle GLUT4 expression may provide benefits in
      addition to improvement of insulin action.

PMID- 11292657
TI  - Fibroblast growth factor receptor 2 (FGFR2) in brain neurons and retinal pigment
      epithelial cells act via stimulation of neuroendocrine L-type channels
      (Ca(v)1.3).
AB  - In contrast to the fibroblast growth factor receptor 1 (FGFR1), little is known
      about intracellular signaling of FGFR2. The signaling cascade of FGFR2 was
      studied using the perforated patch configuration of the patch-clamp technique in
      cultured rat retinal pigment epithelial (RPE) cells that express both FGFR1 and
      FGFR2. Interaction of signaling proteins was studied using immunoprecipitation
      techniques with membrane proteins from RPE cells and freshly isolated rat brain.
      When Ba(2+) currents through L-type channels were studied, extracellular
      application of bFGF (10 ng/ml) led to a shift of the steady-state activation to
      more negative values. In 50% of cells, an additional increase in maximal current
      amplitude was observed. This effect was blocked by the tyrosine kinase inhibitor
      lavendustin A (10(-5) M) but was not influenced by the FGFR1 blocker SU5402 (2 x
      10(-5) M) or by the blocker for src-kinase herbimycin A (10(-5) M).
      Immunoprecipitation of FGFR2 led to coprecipitation of alpha 1D Ca(2+) channel
      subunits and precipitation of alpha 1D subunits led to coprecipitation of FGFR2.
      Immunoprecipitation of FGFR1 did not result in the coprecipitation with alpha 1D
      Ca(2+) channel subunits. The coprecipitation results were comparable when using
      brain tissue and RPE cells. The alpha 1D subunit-specific band were stained with
      antiphosphotyrosine antibodies. We conclude that FGFR2 acts via a different
      signaling cascade than FGFR1. This cascade involves an src-kinase-independent,
      close functional interaction of FGFR2 and the alpha subunit of neuroendocrine L
      type channels.

PMID- 11292658
TI  - Genome-wide search for loci controlling serum IGF binding protein levels of mice.
AB  - A segregating F(2) pedigree based on two mouse lines (DU6i and DBA/2) with
      extremely different growth characteristics was generated to search for loci
      affecting serum levels of insulin-like growth factor (IGF) binding proteins
      (IGFBPs) and to estimate their effects on growth and body composition. DU6i is
      characterized by high body mass and obesity associated with hyperinsulinemia,
      hyperleptinemia, and elevated serum IGF-I concentrations. Furthermore,
      significantly elevated serum levels of IGFBP-2, IGFBP-3, and IGFBP-4 were found
      in DU6i vs. DBA/2 mice. Linkage analysis identified loci with major effects on
      the serum level of IGFBP-3 on Chromosome 5 at 58 cM (Igfbp3q1; F = 9.9) and on
      Chromosome 10 at 46 cM (Igfbp3q2; F = 33.8). A locus significantly influencing
      serum IGFBP-2 levels in males was found on Chromosome 7. Additional linkage was
      detected in males and females for IGFBP-2 on Chromosomes 8, 11, 14, 17, and X,
      and for IGFBP-4 on Chromosome 4. Additional loci affecting IGFBPs acted in a sex
      specific manner. The identified loci coincide in part with chromosomal regions
      controlling growth and obesity. Thus, multiple genes or pleiotropic gene effects
      may be assumed for these chromosomal regions. The identification of quantitative
      trait loci for IGFBPs as subcomponents of growth regulation and differentiation
      will further improve the understanding of complex trait regulation.

PMID- 11292659
TI  - Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed
      by breast tumor cells.
AB  - Tumor growth and metastasis are critically dependent on the formation of new
      blood vessels. The present study found that extracellular matrix protein 1
      (ECM1), a newly described secretory glycoprotein, promotes angiogenesis. This was
      initially suggested by in situ hybridization studies of mouse embryos indicating
      that the ECM1 message was associated with blood vessels and its expression
      pattern was similar to that of flk-1, a recognized marker for endothelium. More
      direct evidence for the role of ECM1 in angiogenesis was provided by the fact
      that highly purified recombinant ECM1 stimulated the proliferation of cultured
      endothelial cells and promoted blood vessel formation in the chorioallantoic
      membrane of chicken embryos. Immunohistochemical staining with specific
      antibodies indicated that ECM1 was expressed by the human breast cancer cell
      lines MDA-435 and LCC15, both of which are highly tumorigenic. In addition,
      staining of tissue sections from patients with breast cancer revealed that ECM1
      was present in a significant proportion of primary and secondary tumors.
      Collectively, the results of this study suggest that ECM1 possesses angiogenic
      properties that may promote tumor progression.

PMID- 11292660
TI  - Tumor-induced angiogenesis studied in confrontation cultures of multicellular
      tumor spheroids and embryoid bodies grown from pluripotent embryonic stem cells.
AB  - Tumor vascularization is the rate-limiting step for the progression of cancer.
      Differential steps of tumor-induced angiogenesis were studied by a novel in vitro
      confrontation culture of avascular multicellular prostate tumor spheroids and
      embryoid bodies grown from pluripotent embryonic stem (ES) cells. Vascularization
      in embryoid bodies started on day 5 of cell culture and was paralleled by down
      regulation of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and vascular
      endothelial growth factor (VEGF). In parallel, a dissipation of gradients in the
      pericellular oxygen pressure was observed as measured by O(2)-sensitive
      microelectrodes. After 24--48 h of confrontation culture, cells positive for
      platelet endothelial cell adhesion molecule (PECAM-1) became visible in the
      contact region between the embryoid body and the tumor spheroid and sprouted
      within the confrontation cultures during subsequent days. Tumor-induced
      angiogenesis resulted in growth stimulation of tumor spheroids, disappearance of
      central necrosis and a reduction of the pericellular oxygen pressure.
      Furthermore, tumor vascularization resulted in elevated levels of HIF-1 alpha,
      VEGF, heat shock protein 27 (HSP27), and P-glycoprotein. Tumor-induced
      angiogenesis may augment the oxygen consumption in tumors resulting in an
      increased expression of hypoxia-related, proangiogenic genes as well as of HSP27
      and P-glycoprotein, which are involved in a multidrug resistance phenotype.

PMID- 11292661
TI  - Cyclin D1 is an early target in hepatocyte proliferation induced by thyroid
      hormone (T3).
AB  - The thyroid hormone (T3) affects cell growth, differentiation, and regulates
      metabolic functions via its interaction with the thyroid hormone nuclear
      receptors (TRs). The mechanism by which TRs mediate cell growth is unknown. To
      investigate the mechanisms responsible for the mitogenic effect of T3, we have
      determined changes in activation of transcription factors, mRNA levels of
      immediate early genes, and levels of proteins involved in the progression from G1
      to S phase of the cell cycle. We show that hepatocyte proliferation induced by a
      single administration of T3 to Wistar rats occurred in the absence of activation
      of AP-1, NF-kappa B, and STAT3 or changes in the mRNA levels of the immediate
      early genes c-fos, c-jun, and c-myc. These genes are considered to be essential
      for liver regeneration after partial hepatectomy (PH). On the other hand, T3
      treatment caused an increase in cyclin D1 mRNA and protein levels that occurred
      much more rapidly compared to liver regeneration after 2/3 PH. The early increase
      in cyclin D1 expression was associated with accelerated onset of DNA synthesis,
      as demonstrated by a 20-fold increase of bromodeoxyuridine-positive hepatocytes
      at 12 h after T3 treatment and by a 20-fold increase in mitotic activity at 18 h.
      An early increase of cyclin D1 expression was also observed after treatment with
      nafenopin, a ligand of a nuclear receptor (peroxisome proliferator-activated
      receptor alpha) of the same superfamily of steroid/thyroid receptors. T3
      treatment also resulted in increased expression of cyclin E, E2F, and p107 and
      enhanced phosphorylation of pRb, the ultimate substrate in the pathway leading to
      transition from G1 to S phase. The results demonstrate that cyclin D1 induction
      is one of the earlier events in hepatocyte proliferation induced by T3 and
      suggest that this cyclin might be a common target responsible for the mitogenic
      activity of ligands of nuclear receptors.

PMID- 11292662
TI  - Telomerase expression prevents replicative senescence but does not fully reset
      mRNA expression patterns in Werner syndrome cell strains.
AB  - Reduced replicative capacity is a consistent characteristic of cells derived from
      patients with Werner syndrome. This premature senescence is phenotypically
      similar to replicative senescence observed in normal cell strains and includes
      altered cell morphology and gene expression patterns. Telomeres shorten with in
      vitro passaging of both WRN and normal cell strains; however, the rate of
      shortening has been reported to be faster in WRN cell strains, and the length of
      telomeres in senescent WRN cells appears to be longer than that observed in
      normal strains, leading to the suggestion that senescence in WRN cell strains may
      not be exclusively associated with telomere effects. We report here that the
      telomere restriction fragment length in senescent WRN fibroblasts cultures is
      within the size range observed for normal fibroblasts strains and that the
      expression of a telomerase transgene in WRN cell strains results in lengthened
      telomeres and replicative immortalization, thus indicating that telomere effects
      are the predominant trigger of premature senescence in WRN cells. Microarray
      analyses showed that mRNA expression patterns induced in senescent WRN cells
      appeared similar to those in normal strains and that hTERT expression could
      prevent the induction of most of these genes. However, substantial differences in
      expression were seen in comparisons of early-passage and telomerase-immortalized
      derivative lines, indicating that telomerase expression does not prevent the
      phenotypic drift, or destabilized genotype, resulting from the WRN defect.

PMID- 11292663
TI  - Influence of plasminogen activator inhibitor type 1 on choroidal
      neovascularization.
AB  - High levels of the plasminogen activators, but also their inhibitor, plasminogen
      activator inhibitor 1 (PAI-1), have been documented in neovascularization of
      severe ocular pathologies such as diabetic retinopathy or age-related macular
      degeneration (AMD). AMD is the primary cause of irreversible photoreceptors loss,
      and current therapies are limited. PAI-1 has recently been shown to be essential
      for tumoral angiogenesis. We report here that deficient PAI-1 expression in mice
      prevented the development of subretinal choroidal angiogenesis induced by laser
      photocoagulation. When systemic and local PAI-1 expression was achieved by
      intravenous injection of a replication-defective adenoviral vector expressing
      human PAI-1 cDNA, the wild-type pattern of choroidal angiogenesis was restored.
      These observations demonstrate the proangiogenic activity of PAI-1 not only in
      tumoral models, but also in choroidal experimental neovascularization sharing
      similarities with human AMD. They identify therefore PAI-1 as a potential target
      for therapeutic ocular anti-angiogenic strategies.

PMID- 11292665
TI  - Infection by human varicella-zoster virus confers norepinephrine sensitivity to
      sensory neurons from rat dorsal root ganglia.
AB  - Varicella-zoster virus (VZV) is a widespread human herpes virus causing chicken
      pox on primary infection and persisting in sensory neurons. Reactivation causes
      shingles, which are characterized by severe pain and often lead to postherpetic
      neuralgia. To elucidate the mechanisms of VZV-associated hyperalgesia, we
      elaborated an in vitro model for the VZV infection of sensory neurons from rat
      dorsal root ganglia. Between 35 and 50% of the neurons showed strong expression
      of the immediate-early virus antigens IE62 and IE63 and the late glycoprotein gE.
      When the intracellular calcium concentration was monitored microfluorometrically
      for individual cells after infection, the sensitivity to GABA or capsaicin was
      similar in controls and in VZV-infected neurons. However, the baseline calcium
      concentration was increased. Neurons became de novo sensitive to adrenergic
      stimulation after VZV infection. Norepinephrine-responsive neurons were more
      frequent and calcium responses to norepinephrine were significantly higher after
      infection with wild-type isolates than with the attenuated vaccine strain OKA.
      The adrenergic agonists phenylephrine and isoproterenol had similar efficacy. We
      suggest that the infection with wild-type VZV isolates confers norepinephrine
      sensitivity to sensory neurons by using alpha(1)- and/or beta(1)-adrenergic
      receptors providing a model for the pathophysiology of the severe pain associated
      with the acute reactivation of VZV.

PMID- 11292664
TI  - VEGFR3 gene structure, regulatory region, and sequence polymorphisms.
AB  - Vascular endothelial growth factor receptor 3 (VEGFR-3) is required for
      cardiovascular development during embryogenesis. In adults, this receptor is
      expressed in lymphatic endothelial cells, and mutant VEGFR3 alleles have been
      implicated in human hereditary lymphedema. To better understand the basis of its
      specific endothelial lineage-restricted expression, we have characterized the
      VEGFR3 gene and its regulatory 5' flanking region. The human gene contains 31
      exons, of which exons 30a and 30b are alternatively spliced. The VEGFR3 proximal
      promoter is TATA-less and contains stretches of sequences homologous with the
      mouse Vegfr3 promoter region. In transfection experiments of cultured cells, the
      Vegfr3 promoter was shown to control endothelial cell-specific transcription of
      downstream reporter genes. This result was further confirmed in vivo; in a subset
      of transgenic mouse embryos, a 1.6 kb Vegfr3 promoter fragment directed weak
      lymphatic endothelial expression of the LacZ marker gene. This suggests that
      endothelial cell-specific elements occur in the proximal promoter, although
      further enhancer elements are probably located elsewhere. The sequence,
      organization, and variation in the VEGFR3 gene and its regulatory region provide
      important tools for the molecular genetic analysis of the lymphatic system and
      its disorders.

PMID- 11292666
TI  - Antiangiogenesis signals by endostatin.
AB  - Endostatin is a potent endogenous angiogenesis inhibitor that induces regression
      of tumors in mice. Neither an extracellular receptor for endostatin nor
      intracellular signals that result in the regression of tumor vascular beds have
      been identified. We demonstrate that endostatin, but not angiostatin, at
      comparable concentrations to those used in in vivo animal trials, rapidly down
      regulates many genes in exponentially growing endothelial cells. These include
      immediate early response genes, cell cycle-related genes, and genes regulating
      apoptosis inhibitors, mitogen-activated protein kinases, focal adhesion kinase, G
      protein-coupled receptors mediating endothelial growth, a mitogenic factor,
      adhesion molecules, and cell structure components. Suppression of both apoptosis
      inhibitors and cell proliferation genes may have a limited contribution to the
      antiangiogenesis process because endostatin induces neither apoptosis nor growth
      inhibition, unless studied under reduced serum conditions. In contrast, the
      antimigratory effect of endostatin was rapid and potent even under serum
      supplemented conditions. Endostatin caused gene suppression and migration arrest
      exclusively in endothelial cells, most profoundly in microvascular endothelial
      cells. The c-myc null fibroblasts obtained by targeted homologous recombination
      showed an attenuated migration rate compared with isogenic parental cells,
      whereas the introduction of the c-myc gene into endothelial cells abrogated the
      antimigratory effect of endostatin. Inhibition of E-box-driven transcription by
      overexpressing max or mad suppressed endothelial migration. Thus, rapid down
      regulation of genes by endostatin neither restores proliferating endothelial
      cells to their resting states nor induces apoptosis; rather, it potently inhibits
      endothelial cell migration partly via suppression of c-myc expression.

PMID- 11292667
TI  - The disabled dendritic cell.
AB  - Dendritic cells are important antigen-presenting cells of the immune system that
      induce and modulate immune responses. They interact with T and B lymphocytes as
      well as with natural killer cells to promote activation and differentiation of
      these cells. Dendritic cells generated in vitro from monocytes by use of the
      cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor
      immunity in cancer patients. However, recent studies revealed that the functional
      repertoire of monocyte-derived dendritic cells may be incomplete. Important
      functions of monocyte-derived dendritic cells such as migration or the ability to
      induce natural killer cell activation or type 2 T helper cell differentiation
      appear to be impaired. We propose that all these deficiencies relate to a single
      biochemical deficiency of monocyte-derived dendritic cells. IL-4, which is used
      to generate monocyte-derived dendritic cells, suppresses phospholipase A2, the
      enzyme that liberates arachidonic acid from membrane phospholipids and
      contributes to the synthesis of platelet-activating factor. Monocyte-derived
      dendritic cells must therefore fail to generate platelet-activating factor as
      well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and
      lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet
      activating factor are known to play an important role in processes such as
      leukocyte migration, natural killer cell activation, and type 2 T helper cell
      differentiation, the deficiency in eicosanoid and platelet-activating factor
      biosynthesis may be responsible for the observed handicaps of monocyte-derived
      dendritic cells.

PMID- 11292668
TI  - Involvement of Rho-kinase in hypertensive vascular disease: a novel therapeutic
      target in hypertension.

PMID- 11292669
TI  - Morphological aspects of spinal cord autoimmune neuroprotection: colocalization
      of T cells with B7--2 (CD86) and prevention of cyst formation.

PMID- 11292670
TI  - Ganglioside GD3 enhances apoptosis by suppressing the nuclear factor-kappa B
      dependent survival pathway.

PMID- 11292671
TI  - Protein expression of UCP3 differs between human type 1, type 2a, and type 2b
      fibers.

PMID- 11292672
TI  - Increased brain histamine in an alcohol-preferring rat line and modulation of
      ethanol consumption by H(3) receptor mechanisms.

PMID- 11292673
TI  - Myoglobin facilitates oxygen diffusion.

PMID- 11292674
TI  - Prosaptide D5, a retro-inverso 11-mer peptidomimetic, rescued dopaminergic
      neurons in a model of Parkinson's disease.

PMID- 11292675
TI  - Acidic pH-induced folding of annexin VI is a prerequisite for its insertion into
      lipid bilayers and formation of ion channels by the protein molecules.

PMID- 11292676
TI  - Presence of B7--2 (CD86) and lack of B7--1 (CD(80) on myelin phagocytosing MHC-II
      positive rat microglia is associated with nondestructive immunity in vivo.

PMID- 11292677
TI  - Gamma-aminobutyric acid (GABA): a para- and/or autocrine hormone in the
      pituitary.

PMID- 11292678
TI  - Structures outside the basal ganglia may compensate for dopamine loss in the
      presymptomatic stages of Parkinson's disease.

PMID- 11292679
TI  - Identification of the human analog of SR-BI and LOX-1 as receptors for
      hypochlorite-modified high density lipoprotein on human umbilical venous
      endothelial cells.

PMID- 11292680
TI  - Expression of human collagenase-3 (MMP-13) by fetal skin fibroblasts is induced
      by transforming growth factor beta via p38 mitogen-activated protein kinase.

PMID- 11292681
TI  - Insulin resistance with low cellular IRS-1 expression is also associated with low
      GLUT4 expression and impaired insulin-stimulated glucose transport.

PMID- 11292682
TI  - The effect of weightlessness on cytoskeleton architecture and proliferation of
      human breast cancer cell line MCF-7.

PMID- 11292683
TI  - Amphiphilic, tri-block copolymers provide potent membrane-targeted
      neuroprotection.

PMID- 11292684
TI  - Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine
      expression, and inhibits glucocorticoid actions in alveolar macrophages.

PMID- 11292685
TI  - Involvement of sphingomyelinase in insulin-induced phosphatidylinositol 3-kinase
      activation.

PMID- 11292688
TI  - Protection of mice with a tuberculosis subunit vaccine based on a fusion protein
      of antigen 85b and esat-6.
AB  - In this study, we investigated the potential of a tuberculosis subunit vaccine
      based on fusion proteins of the immunodominant antigens ESAT-6 and antigen 85B.
      When the fusion proteins were administered to mice in the adjuvant combination
      dimethyl dioctadecylammonium bromide-monophosphoryl lipid A, a strong dose
      dependent immune response was induced to both single components as well as to the
      fusion proteins. The immune response induced was accompanied by high levels of
      protective immunity and reached the level of Mycobacterium bovis BCG-induced
      protection over a broad dose range. The vaccine induced efficient immunological
      memory, which remained stable 30 weeks postvaccination.

PMID- 11292689
TI  - Identification of attenuated Yersinia pseudotuberculosis strains and
      characterization of an orogastric infection in BALB/c mice on day 5 postinfection
      by signature-tagged mutagenesis.
AB  - Yersinia pseudotuberculosis localizes to the distal ileum, cecum, and proximal
      colon of the gastrointestinal tract after oral infection. Using signature-tagged
      mutagenesis, we isolated 13 Y. pseudotuberculosis mutants that failed to survive
      in the cecum of mice after orogastric inoculation. Twelve of these mutants were
      also attenuated for replication in the spleen after intraperitoneal infection,
      whereas one strain, mutated the gene encoding invasin, replicated as well as wild
      type bacteria in the spleen. Several mutations were in operons encoding
      components of the type III secretion system, including components involved in
      translocating Yop proteins into host cells. This indicates that one or more Yops
      may be necessary for survival in the gastrointestinal tract. Three mutants were
      defective in O-antigen biosynthesis; these mutants were also unable to invade
      epithelial cells as efficiently as wild-type Y. pseudotuberculosis. Several other
      mutations were in genes that had not previously been associated with growth in a
      host, including cls, ksgA, and sufl. In addition, using Y. pseudotuberculosis
      strains marked with signature tags, we counted the number of different bacterial
      clones that were present in the cecum, mesenteric lymph nodes, and spleen 5 days
      postinfection. We find barriers in the host animal that limit the number of
      bacteria that succeed in reaching and/or replicating in the mesenteric lymph
      nodes and spleen after breaching the gut mucosa.

PMID- 11292690
TI  - Upregulation of toll-like receptor 2 gene expression in macrophage response to
      peptidoglycan and high concentration of lipopolysaccharide is involved in NF
      kappa b activation.
AB  - Toll-like receptors 2 and 4 (TLR2 and TLR4) have been found to transduce signals
      of peptidoglycan (PGN) and lipopolysaccharide (LPS), respectively, for NF-kappa B
      activation. However, little is known about the expression and regulation of the
      TLR2 gene in monocytes/macrophages in response to the two typical bacterial
      products. We show in the present study that both PGN and a high concentration of
      LPS increase TLR2 gene expression in macrophage-like cells, 1 alpha,25
      dihydroxyvitamin D(3)-differentiated human HL60 and mouse RAW264.7 cells, and
      human monocytes in a dose- and time-dependent manner. Actinomycin D and
      pyrrolidine dithiocarbamate inhibition of gene transcription and NF-kappa B
      activation, respectively, blocks LPS- and PGN-elevated TLR2 mRNA in monocytic
      cells. The LPS-induced increase in TLR2 mRNA in monocytic cells is abolished by
      polymyxin B pretreatment and is observed in peripheral blood mononuclear cells
      from pigs subjected to endotoxic shock. Further, high concentrations of LPS and
      synthetic lipid A increase TLR2 mRNA expression in peritoneal macrophages from
      both TLR4-deficient C3H/HeJ mice and normal C3H/HeN mice, a process that
      constitutes induction of TLR4-independent TLR2 expression. These findings
      demonstrate that TLR2 gene expression is upregulated in macrophage responses to
      PGN and to high concentrations of LPS in vitro and in vivo and correlates with NF
      kappa B activation.

PMID- 11292691
TI  - Monocytes augment bacterial species- and strain-dependent induction of tissue
      factor activity in bacterium-infected human vascular endothelial cells.
AB  - In bacterial endocarditis (BE), intravascular infection with Staphylococcus
      aureus, Streptococcus sanguis, or Staphylococcus epidermidis can lead to
      formation of a fibrin clot on the inner surface of the heart and cause heart
      dysfunction. The events that start the coagulation in the early stage of the
      disease are largely unknown. We have recently shown that human endothelial cells
      (EC) upon binding and internalization of S. aureus, but not S. sanguis or S.
      epidermidis, express tissue factor (TF)-dependent procoagulant activity (TFA).
      The present study shows that infection of EC with these three pathogens induces
      surface expression of intracellular adhesion molecule 1 (ICAM-1) and vascular
      cell adhesion molecule 1 (VCAM-1) and monocyte adhesion. Subsequent coculture of
      these cells synergistically enhanced TFA, which was exclusively dependent on TF
      molecules that were expressed on EC during coculture. TFA induction required
      direct contact between monocytes and bacterium-infected EC, but the signals for
      this response were not generated by the binding of monocytes through their
      beta(2)- or alpha(4)-integrins to ICAM-1 or VCAM-1, respectively, on infected EC.
      The mechanism by which monocytes induce TFA in bacterium-infected EC was partly
      mediated by the proinflammatory cytokine interleukin-1 produced by the cells
      during coculture. Endogenous tumor necrosis factor alpha was not involved. This
      modulating effect of monocytes on species- and strain-dependent TFA of bacterium
      infected EC supports our hypothesis that in an early stage in the pathogenesis of
      BE, as well as other intravascular infections that lead to detrimental fibrin
      formation, the coagulation cascade can be activated on the surfaces of EC as a
      consequence of specific interactions between pathogenic bacteria, EC, and
      monocytes.

PMID- 11292692
TI  - Role of mannoprotein in induction and regulation of immunity to Cryptococcus
      neoformans.
AB  - Our previous observations showed that mannoprotein (MP) induces early and massive
      production of interleukin-12 (IL-12) in vitro. This study was designed to
      investigate whether this phenomenon could be applied in vivo and to determine the
      biological significance of MP in Cryptococcus neoformans infection. The results
      reported here show that MP treatment induces IL-12 secretion by splenic
      macrophages and IL-12 p40 mRNA in the brain. During C. neoformans infection, MP
      reinforced IL-12 and IFN-gamma secretion that coincided with enhanced antifungal
      activity of natural effector cells, early resolution of the inflammatory process,
      and clearance of fungal load from the brain. These studies show that MP is a key
      inflammatory mediator that induces a protective immune response against C.
      neoformans infection. This information can be used to facilitate the design of a
      rational approach to manipulate the immune response to C. neoformans.

PMID- 11292693
TI  - Inhibition of hydrophobic protein-mediated Candida albicans attachment to
      endothelial cells during physiologic shear flow.
AB  - Adhesion interactions during hematogenous dissemination of Candida albicans
      likely involve a complex array of host and fungal factors. Possible C. albicans
      factors include changes in cell surface hydrophobicity and exposed antigens that
      have been shown in static adhesion assays to influence attachment events. We used
      a novel in vitro shear analysis system to investigate host-pathogen interactions
      and the role of fungal cell surface hydrophobicity in adhesion events with human
      endothelial cells under simulated physiologic shear. Endothelial monolayers were
      grown in capillary tubes and tested with and without interleukin-1 beta
      activation in buffered medium containing human serum. Hydrophobic and hydrophilic
      stationary-phase C. albicans yeast cells were infused into the system under shear
      flow and found to adhere with widely varying efficiencies. The average number of
      adherent foci was determined from multiple fields, sampled via video microscopy,
      between 8 and 12 min after infusion. Hydrophobic C. albicans cells demonstrated
      significantly more heterotypic binding events (Candida-endothelial cell) and
      greater homotypic binding events (Candida-Candida) than hydrophilic yeast cells.
      Cytokine activation of the endothelium significantly increased binding by
      hydrophobic C. albicans compared to unactivated host cells. Preincubation of
      hydrophobic yeast cells with a monoclonal antibody against hydrophobic cell wall
      proteins significantly blocked adhesion interactions with the endothelial
      monolayers. Because the antibody also blocks C. albicans binding to laminin and
      fibronectin, results suggest that vascular adhesion events with endothelial cells
      and exposed extracellular matrix may be blocked during C. albicans dissemination.
      Future studies will address the protective efficacy of blocking or redirecting
      blood-borne fungal cells to favor host defense mechanisms.

PMID- 11292694
TI  - Distribution and kinetics of lipoprotein-bound endotoxin.
AB  - Lipopolysaccharide (LPS), the major glycolipid component of gram-negative
      bacterial outer membranes, is a potent endotoxin responsible for
      pathophysiological symptoms characteristic of infection. The observation that the
      majority of LPS is found in association with plasma lipoproteins has prompted the
      suggestion that sequestering of LPS by lipid particles may form an integral part
      of a humoral detoxification mechanism. Previous studies on the biological
      properties of isolated lipoproteins used differential ultracentrifugation to
      separate the major subclasses. To preserve the integrity of the lipoproteins, we
      have analyzed the LPS distribution, specificity, binding capacity, and kinetics
      of binding to lipoproteins in human whole blood or plasma by using high
      performance gel permeation chromatography and fluorescent LPS of three different
      chemotypes. The average distribution of O111:B4, J5, or Re595 LPS in whole blood
      from 10 human volunteers was 60% (+/-8%) high-density lipoprotein (HDL), 25% (+/
      7%) low-density lipoprotein, and 12% (+/-5%) very low density lipoprotein. The
      saturation capacity of lipoproteins for all three LPS chemotypes was in excess of
      200 microg/ml. Kinetic analysis however, revealed a strict chemotype dependence.
      The binding of Re595 or J5 LPS was essentially complete within 10 min, and
      subsequent redistribution among the lipoprotein subclasses occurred to attain
      similar distributions as O111:B4 LPS at 40 min. We conclude that under simulated
      physiological conditions, the binding of LPS to lipoproteins is highly specific,
      HDL has the highest binding capacity for LPS, the saturation capacity of
      lipoproteins for endotoxin far exceeds the LPS concentrations measured in
      clinical situations, and the kinetics of LPS association with lipoproteins
      display chemotype-dependent differences.

PMID- 11292695
TI  - Characterization of the Yersinia pestis Yfu ABC inorganic iron transport system.
AB  - In Yersinia pestis, the causative agent of plague, two inorganic iron transport
      systems have been partially characterized. The yersiniabactin (Ybt) system is a
      siderophore-dependent transport system required for full virulence. Yfe is an ABC
      transport system that accumulates both iron and manganese. We have identified and
      cloned a Y. pestis yfuABC operon. The YfuABC system is a member of the cluster of
      bacterial ABC iron transporters that include Sfu of Serratia, Hit of Haemophilus,
      and Yfu of Yersinia enterocolitica. The Y. pestis KIM6+ system is most homologous
      to that in Y. enterocolitica, showing identities of 84% for YfuA (periplasmic
      binding protein), 87% for YfuB (inner membrane permease), and 75% for YfuC (ATP
      hydrolase). We constructed a yfuABC promoter-lacZ fusion to examine regulation of
      transcription. This promoter contains a potential Fur binding sequence and is
      iron and Fur regulated. Significant expression from the yfuABC promoter occurred
      during iron-deficient growth conditions. In vitro transcription and translation
      of a recombinant plasmid encoding yfuABC indicates that YfuABC proteins are
      expressed. Escherichia coli 1017 (an enterobactin-deficient mutant) carrying this
      plasmid was able to grow in an iron-restrictive complex medium. We constructed a
      deletion encompassing the yfuABC promoter and most of yfuA. This mutation was
      introduced into strains with mutations in Ybt, Yfe, or both systems to examine
      the role of Yfu in iron acquisition in Y. pestis. Growth of the yfu mutants in a
      deferrated, defined medium (PMH2) at 26 and 37 degrees C failed to identify a
      growth or iron transport defect due to the yfu mutation. Fifty percent lethal
      dose studies in mice did not demonstrate a role for the Yfu system in mammalian
      virulence.

PMID- 11292696
TI  - In vivo dynamics of type 1 fimbria regulation in uropathogenic Escherichia coli
      during experimental urinary tract infection.
AB  - Escherichia coli is the primary cause of uncomplicated infections of the urinary
      tract including cystitis. More serious infections, characterized as acute
      pyelonephritis, can also develop. Type 1 fimbriae of E. coli contribute to
      virulence in the urinary tract; however, only recently has the expression of the
      type 1 fimbriae been investigated in vivo using molecular techniques.
      Transcription of type 1 fimbrial genes is controlled by a promoter that resides
      on a 314-bp invertible element capable of two orientations. One places the
      promoter in the ON orientation, allowing for transcription; the other places the
      promoter in the OFF orientation, preventing transcription. A PCR-based assay was
      developed to measure the orientation of the invertible element during an
      experimental urinary tract infection in mice. Using this assay, it was found that
      the percentage of the population ON in urine samples correlated with the
      respective CFU per gram of bladder (P = 0.0006) but not with CFU per gram of
      kidney (P > 0.069). Cystitis isolates present in the urine of mice during the
      course of infection had a higher percentage of their invertible elements in the
      ON orientation than did pyelonephritis isolates (85 and 34%, respectively, at 24
      h; P < 0.0001). In general, cystitis isolates, unlike pyelonephritis isolates,
      were more likely to maintain their invertible elements in the ON orientation for
      the entire period of infection. E. coli cells expressing type 1 fimbriae,
      expelled in urine, were shown by scanning electron microscopy to be densely
      packed on the surface of uroepithelial cells. These results suggest that
      expression of type 1 fimbriae is more critical for cystitis strains than for
      pyelonephritis strains in the early stages of an infection during bladder
      colonization.

PMID- 11292697
TI  - Gamma interferon and lipopolysaccharide interact at the level of transcription to
      induce tumor necrosis factor alpha expression.
AB  - Lipopolysaccharide (LPS) is a very potent inducer of tumor necrosis factor alpha
      (TNF-alpha) expression from monocytes and macrophages. Another inflammatory
      cytokine, gamma interferon (IFN-gamma), can potentiate the effects of LPS, but
      the mechanism is not thoroughly understood. Previous reports emphasized the
      ability of IFN-gamma to upregulate CD14 expression (the receptor for LPS), and
      nearly all studies have utilized sequential stimulation with IFN-gamma followed
      by LPS to exploit this phenomenon. This study demonstrates that IFN-gamma can
      upregulate the effect of LPS at the level of transcription. Human monoblastic
      Mono-Mac-6 cells produced up to threefold-greater levels of TNF-alpha when
      simultaneously stimulated with LPS and IFN-gamma compared to treatment with LPS
      alone. RNase protection studies showed a similar increase in RNA beginning as
      early as within 30 min. The synthesis of TNF-alpha mRNA in IFN-gamma- and LPS
      treated Mono-Mac-6 cells was also temporally prolonged even though the message
      turnover rate was identical to that seen in LPS stimulated cells. The modulatory
      effect of IFN-gamma may be mediated by Jak2.

PMID- 11292698
TI  - Induction of systemic antifimbria and antitoxin antibody responses in Egyptian
      children and adults by an oral, killed enterotoxigenic Escherichia coli plus
      cholera toxin B subunit vaccine.
AB  - We assessed serologic responses to an oral, killed whole-cell enterotoxigenic
      Escherichia coli plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian
      adults, 105 schoolchildren, and 93 preschool children. Each subject received two
      doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7
      days after each dose. Plasma antibodies to rCTB and four vaccine-shared
      colonization factors (CFs) were measured by enzyme-linked immunosorbent assay.
      Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all
      subjects, and those against CS1, CS2, and CS4 were measured in all children plus
      a subset of 33 adults. IgG antibodies to these five antigens were measured in a
      subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2
      fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was
      observed in 94 to 95% of adult vaccinees, with titer increases as robust as those
      previously reported for these two pediatric cohorts. The proportion showing IgA
      seroconversion to each CF antigen among vaccinated children (range, 70 to 96%)
      and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and
      adults (25 to 81%), was significantly higher than the corresponding proportion in
      placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers
      peaked after one dose in children, whereas in all age groups IgG antibodies rose
      incrementally after each dose. Independently, both preimmunization IgA titer and
      age were inversely related to the magnitude of IgA responses. In conclusion,
      serologic responses to the ETEC-rCTB vaccine may serve as practical immune
      outcome measures in future pediatric trials in areas where ETEC is endemic.

PMID- 11292699
TI  - Arg-gingipain a DNA vaccine induces protective immunity against infection by
      Porphyromonas gingivalis in a murine model.
AB  - Arginine-specific cysteine proteinases (RgpA and RgpB) produced by the
      periodontal pathogen Porphyromonas gingivalis are suspected virulence factors and
      are involved in interrupting host defense mechanisms as well as in penetrating
      and destroying periodontal connective tissues. To induce a protective immune
      response against P. gingivalis, we constructed an rgpA DNA vaccine. BALB/c mice
      were immunized intradermally by Gene Gun with plasmid DNA carrying rgpA. Antibody
      responses against P. gingivalis were determined by an enzyme-linked immunosorbent
      assay. The rgpA DNA vaccine induced high levels of serum antibodies against P.
      gingivalis. Sera from the rgpA DNA vaccine-immunized mice diminished the
      proteolytic activity of RgpA and RgpB and inhibited the binding of P. gingivalis
      to a type I collagen sponge. Moreover, the sera effectively reduced the
      hemagglutination of P. gingivalis, indicating that the hemagglutinin activity of
      the organism is associated with RgpA. We found with a murine abscess model that
      mice immunized with the rgpA DNA vaccine were resistant to an invasive P.
      gingivalis W50 challenge. These results suggest that the rgpA DNA vaccine induced
      specific antibodies against the enzyme and that this vaccine could confer
      protective immunity against P. gingivalis infection.

PMID- 11292700
TI  - Gender is a major factor in determining the severity of mycoplasma respiratory
      disease in mice.
AB  - Gender is a significant factor in determining the susceptibility to and severity
      of pulmonary diseases in both humans and animals. Murine respiratory
      mycoplasmosis (MRM), due to Mycoplasma pulmonis infection, is an excellent animal
      model for evaluation of the role of various host factors on the development of
      acute or chronic inflammatory lung diseases. MRM has many similarities to
      mycoplasma respiratory disease in humans. The purpose of the present study was to
      determine whether gender has a significant impact on lung disease due to M.
      pulmonis infection in mice. It was demonstrated that male mice consistently
      developed more severe disease in the lung parenchyma than did female mice. There
      was no gender difference in disease severity along the airways or any difference
      in mycoplasma numbers in lungs of male and female mice. Furthermore, surgical
      removal of reproductive organs reduced the severity of mycoplasma disease and the
      numbers of mycoplasma organisms recovered from lungs. Thus, gender plays a
      significant role in determining the severity of M. pulmonis disease. In fact, the
      gender of the host was a major factor in determining whether an acute or chronic
      inflammatory lung disease developed after infection with M. pulmonis.

PMID- 11292701
TI  - Staphylococcus aureus fibronectin binding proteins are essential for
      internalization by osteoblasts but do not account for differences in
      intracellular levels of bacteria.
AB  - Staphylococcus aureus is a major pathogen of bone that has been shown to be
      internalized by osteoblasts via a receptor-mediated pathway. Here we report that
      there are strain-dependent differences in the uptake of S. aureus by osteoblasts.
      An S. aureus septic arthritis isolate, LS-1, was internalized some 10-fold more
      than the laboratory strain 8325-4. Disruption of the genes for the fibronectin
      binding proteins in these two strains of S. aureus blocked their ability to be
      internalized by osteoblasts, thereby demonstrating the essentiality of these
      genes in this process. However, there were no differences in the capacity of
      these two strains to bind to fibronectin or osteoblasts. Analysis of the kinetics
      of internalization of the two strains by osteoblasts revealed that strain 8325-4
      was internalized only over a short period of time (2 h) and to low numbers, while
      LS-1 was taken up by osteoblasts in large numbers for over 3 h. These differences
      in the kinetics of uptake explain the fact that the two strains of S. aureus are
      internalized by osteoblasts to different extents and suggest that in addition to
      the fibronectin binding proteins there are other, as yet undetermined virulence
      factors that play a role in the internalization process.

PMID- 11292702
TI  - Recombinant urease and urease DNA of Coccidioides immitis elicit an
      immunoprotective response against coccidioidomycosis in mice.
AB  - Coccidioides immitis antigens which stimulate a T helper cell 1 (Th1) pathway of
      host immune response are considered to be essential components of a vaccine
      against coccidioidomycosis. Recombinant urease (rURE) and recombinant heat shock
      protein 60 (rHSP60) of C. immitis were expressed in Escherichia coli and tested
      as vaccine candidates in BALB/c mice. A synthetic oligodeoxynucleotide which
      contained unmethylated CpG dinucleotides and was previously shown to enhance a
      murine Th1 response was used as an immunoadjuvant. T cells isolated from the
      spleens and lymph nodes of the rURE- and rHSP60-immune mice showed in vitro
      proliferative responses to the respective recombinant protein, but only those T
      lymphocytes from rURE-immunized mice revealed markedly elevated levels of
      expression of selected Th1-type cytokine genes. BALB/c mice immunized
      subcutaneously with rURE and subsequently challenged by the intraperitoneal
      (i.p.) route with a lethal inoculum of C. immitis arthroconidia demonstrated a
      significant reduction in the level of C. immitis infection compared to control
      animals. rHSP60 was much less effective as a protective antigen. Evaluation of
      cytokine gene expression in lung tissue and levels of recombinant urease-specific
      immunoglobulins (immunoglobulin G1 [IgG1] versus IgG2a) in murine sera at 12 days
      after challenge provided additional evidence that immunization with rURE
      stimulated a Th1 response to the pathogen. Urease was further evaluated by
      expression of the URE gene in a mammalian plasmid vector (pSecTag2A.URE) which
      was used to immunize mice by the intradermal route. In this case, 82% of the
      vector construct-immunized animals survived more than 40 days after i.p.
      infection, compared to only 10% of the mice immunized with the vector alone. In
      addition, 87% of the pSecTag2A.URE-immunized survivors had sterile lungs and
      spleens. These data support the need for further evaluation of the C. immitis
      urease as a candidate vaccine against coccidioidomycosis.

PMID- 11292703
TI  - Search for correlates of protective immunity conferred by anthrax vaccine.
AB  - Vaccination by anthrax protective antigen (PA)-based vaccines requires multiple
      immunization, underlying the need to develop more efficacious vaccines or
      alternative vaccination regimens. In spite of the vast use of PA-based vaccines,
      the definition of a marker for protective immunity is still lacking. Here we
      describe studies designed to help define such markers. To this end we have
      immunized guinea pigs by different methods and monitored the immune response and
      the corresponding extent of protection against a lethal challenge with anthrax
      spores. Active immunization was performed by a single injection using one of two
      methods: (i) vaccination with decreasing amounts of PA and (ii) vaccination with
      constant amounts of PA that had been thermally inactivated for increasing
      periods. In both studies a direct correlation between survival and neutralizing
      antibody titer was found (r(2) = 0.92 and 0.95, respectively). Most
      significantly, in the two protocols a similar neutralizing-antibody titer range
      provided 50% protection. Furthermore, in a complementary study involving passive
      transfer of PA hyperimmune sera to naive animals, a similar correlation between
      neutralizing-antibody titers and protection was found. In all three immunization
      studies, neutralization titers of at least 300 were sufficient to confer
      protection against a dose of 40 50% lethal doses (LD(50)) of virulent anthrax
      spores of the Vollum strain. Such consistency in the correlation of protective
      immunity with anti-PA antibody titers was not observed for antibody titers
      determined by an enzyme-linked immunosorbent assay. Taken together, these results
      clearly demonstrate that neutralizing antibodies to PA constitute a major
      component of the protective immunity against anthrax and suggest that this
      parameter could be used as a surrogate marker for protection.

PMID- 11292704
TI  - Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene
      sequences.
AB  - Salmonella enterica serotype Typhi differs from nontyphoidal Salmonella serotypes
      by its strict host adaptation to humans and higher primates. Since fimbriae have
      been implicated in host adaptation, we investigated whether the serotype Typhi
      genome contains fimbrial operons which are unique to this pathogen or restricted
      to typhoidal Salmonella serotypes. This study established for the first time the
      total number of fimbrial operons present in an individual Salmonella serotype.
      The serotype Typhi CT18 genome, which has been sequenced by the Typhi Sequencing
      Group at the Sanger Centre, contained a type IV fimbrial operon, an orthologue of
      the agf operon, and 12 putative fimbrial operons of the chaperone-usher assembly
      class. In addition to sef, fim, saf, and tcf, which had been described previously
      in serotype Typhi, we identified eight new putative chaperone-usher-dependent
      fimbrial operons, which were termed bcf, sta, stb, ste, std, stc, stg, and sth.
      Hybridization analysis performed with 16 strains of Salmonella reference
      collection C and 22 strains of Salmonella reference collection B showed that all
      eight putative fimbrial operons of serotype Typhi were also present in a number
      of nontyphoidal Salmonella serotypes. Thus, a simple correlation between host
      range and the presence of a single fimbrial operon seems at present unlikely.
      However, the serotype Typhi genome differed from that of all other Salmonella
      serotypes investigated in that it contained a unique combination of putative
      fimbrial operons.

PMID- 11292706
TI  - Identification of continuous B-cell epitopes on the protein moiety of the 58
      kiloDalton cell wall mannoprotein of Candida albicans belonging to a family of
      immunodominant fungal antigens.
AB  - The 58-kiloDalton mannoprotein (mp58) on the surface of Candida albicans is
      highly immunogenic, is expressed by all C. albicans isolates tested, and elicits
      strong antibody responses during candidiasis. It belongs to a family of
      immunodominant fungal antigens with representatives also in different species of
      Aspergillus. The amino acid sequence of the protein portion of mp58 as deduced
      from the DNA sequence of its encoding gene (FBP1/PRA1) was used to synthesize a
      complete set of overlapping dodecapeptides (overlap, 7; offset, 5) covalently
      attached to the surface of derivatized polyethylene pins. The pin-coupled
      peptides were used in a modified enzyme-linked immunosorbent assay (ELISA) to
      identify continuous epitopes recognized by a number of antiserum preparations
      containing anti-mp58 antibodies. This comprehensive epitope-scanning study
      revealed the presence of multiple immunoreactive continuous B-cell epitopes
      within the protein sequence. Regions of increased reactivity included both the
      amino and carboxy termini of the mature protein (encompassing amino acid residues
      16 to 50 and 286 to 299, respectively) and four internal regions spanning amino
      acids at positions 66 to 92, 121 to 142, 148 to 192, and 211 to 232. Further
      delineation of epitopic regions and identification of the boundaries of the
      antigenic sites was performed upon ELISA testing with a second Pepset consisting
      of completely overlapping 8-mer peptides spanning these reactive regions in the
      protein moiety of mp58. The highly reactive epitopic region at the C terminus of
      the protein was further evaluated using both window net and replacement net
      analyses. A synthetic peptide corresponding to the last 10 amino acid residues at
      the C terminus of the protein was immunogenic when injected into mice after being
      coupled to a carrier protein. Moreover, antibodies in the resulting sera
      specifically recognized the homologous mp58 in ELISAs and immunoblot assays.
      Delineation of the antibody responses to mp58 could provide the basis for the
      development of novel immunity-based prophylactic, therapeutic, and diagnostic
      techniques for the management of candidiasis.

PMID- 11292707
TI  - Requirement of non-T cells that produce gamma interferon for prevention of
      reactivation of Toxoplasma gondii infection in the brain.
AB  - We examined the mechanism of resistance against reactivation of infection with
      Toxoplasma gondii in the brain. BALB/c-background gamma interferon (IFN-gamma)
      knockout (IFN-gamma(-/-)) and control mice were infected and treated with
      sulfadiazine beginning 4 days after infection for 3 weeks. After discontinuation
      of treatment, IFN-gamma(-/-) mice succumbed to toxoplasmic encephalitis (TE) and
      died, whereas control animals did not develop TE and survived. Adoptive transfer
      of immune spleen cells from infected control mice did not prevent development of
      TE or mortality in the IFN-gamma(-/-) mice. To examine whether the failure of the
      cell transfer to protect against TE is unique to IFN-gamma(-/-) mice, athymic
      nude and SCID mice that lack T cells were infected and injected with the immune
      spleen or T cells in the same manner as IFN-gamma(-/-) mice. Whereas control nude
      and SCID mice that had not received the immune cells developed severe TE and died
      after discontinuation of sulfadiazine, those that had received the cells did not
      develop TE and survived. Before cell transfer, IFN-gamma mRNA was detected in
      brains of infected nude and SCID but not in brains of IFN-gamma(-/-) mice. IFN
      gamma mRNA was also detected in brains of infected SCID mice depleted of NK cells
      by treatment with anti-asialo GM1 antibody, and such animals did not develop TE
      after receiving immune T cells. Thus, IFN-gamma production by non-T cells, in
      addition to T cells, is required for prevention of reactivation of T. gondii
      infection in the brain. The IFN-gamma-producing non-T cells do not appear to be
      NK cells.

PMID- 11292705
TI  - Role of Helicobacter pylori cag region genes in colonization and gastritis in two
      animal models.
AB  - The Helicobacter pylori chromosomal region known as the cytotoxin-gene associated
      pathogenicity island (cag PAI) is associated with severe disease and encodes
      proteins that are believed to induce interleukin (IL-8) secretion by cultured
      epithelial cells. The objective of this study was to evaluate the relationship
      between the cag PAI, induction of IL-8, and induction of neutrophilic gastric
      inflammation. Germ-free neonatal piglets and conventional C57BL/6 mice were given
      wild-type or cag deficient mutant derivatives of H. pylori strain 26695 or SS1.
      Bacterial colonization was determined by plate count, gastritis and neutrophilic
      inflammation were quantified, and IL-8 induction in AGS cells was determined by
      enzyme-linked immunosorbent assay. Deletion of the entire cag region or
      interruption of the virB10 or virB11 homolog had no effect on bacterial
      colonization, gastritis, or neutrophilic inflammation. In contrast, these
      mutations had variable effects on IL-8 induction, depending on the H. pylori
      strain. In the piglet-adapated strain 26695, which induced IL-8 secretion by AGS
      cells, deletion of the cag PAI decreased induction. In the mouse-adapted strain
      SS1, which did not induce IL-8 secretion, deletion of the cagII region or
      interruption of any of three cag region genes increased IL-8 induction. These
      results indicate that in mice and piglets (i) neither the cag PAI nor the ability
      to induce IL-8 in vitro is essential for colonization or neutrophilic
      inflammation and (ii) there is no direct relationship between the presence of the
      cag PAI, IL-8 induction, and neutrophilic gastritis.

PMID- 11292708
TI  - Oral immunization with recombinant Streptococcus gordonii expressing
      porphyromonas gingivalis FimA domains.
AB  - Porphyromonas gingivalis, a gram-negative anaerobe, is implicated in the etiology
      of adult periodontitis. P. gingivalis fimbriae are one of several critical
      surface virulence factors involved in both bacterial adherence and inflammation.
      P. gingivalis fimbrillin (FimA), the major subunit protein of fimbriae, is
      considered an important antigen for vaccine development against P. gingivalis
      associated periodontitis. We have previously shown that biologically active
      domains of P. gingivalis fimbrillin can be expressed on the surface of the human
      commensal bacterium Streptococcus gordonii. In this study, we examined the
      effects of oral coimmunization of germfree rats with two S. gordonii recombinants
      expressing N (residues 55 to 145)- and C (residues 226 to 337)-terminal epitopes
      of P. gingivalis FimA to elicit FimA-specific immune responses. The effectiveness
      of immunization in protecting against alveolar bone loss following P. gingivalis
      infection was also evaluated. The results of this study show that the oral
      delivery of P. gingivalis FimA epitopes via S. gordonii vectors resulted in the
      induction of FimA-specific serum (immunoglobulin G [IgG] and IgA) and salivary
      (IgA) antibody responses and that the immune responses were protective against
      subsequent P. gingivalis-induced alveolar bone loss. These results support the
      potential usefulness of the S. gordonii vectors expressing P. gingivalis
      fimbrillin as a mucosal vaccine against adult periodontitis.

PMID- 11292710
TI  - Spa contributes to the virulence of type 18 group A streptococci.
AB  - Streptococcal protective antigen (Spa) is a newly described surface protein of
      group A streptococci that was recently shown to evoke protective antibodies (J.
      B. Dale, E. Y. Chiang, S. Liu, H. S. Courtney, and D. L. Hasty, J. Clin.
      Investig. 103:1261--1268, 1999). In this study, we have determined the complete
      sequence of the spa gene from type 18 streptococci. Purified, recombinant Spa
      protein evoked antibodies that were bactericidal against type 18 streptococci,
      confirming the presence of protective epitopes. Sera from patients with acute
      rheumatic fever contained antibodies against recombinant Spa, indicating that the
      Spa protein is expressed in vivo and is immunogenic in humans. To determine the
      role of Spa in the virulence of group A streptococci, we created a series of
      insertional mutants that were (i) Spa negative and M18 positive, (ii) Spa
      positive and M18 negative, and (iii) Spa negative and M18 negative. The mutants
      and the parent M18 strain (18-282) were used in assays to determine resistance to
      phagocytosis, growth in human blood, and mouse virulence. The results show that
      Spa is a virulence determinant of group A streptococci and that expression of
      both Spa and M18 is required for optimal virulence of type 18 streptococci.

PMID- 11292709
TI  - Effective in vitro clearance of Porphyromonas gingivalis by Fc alpha receptor I
      (CD89) on gingival crevicular neutrophils.
AB  - Porphyromonas gingivalis has been implicated as a causative pathogen in
      periodontitis. Immunotherapeutic approaches have recently been suggested to aid
      in the clearance of P. gingivalis from disease sites. Because antibody-Fc
      receptor (FcR) interactions play a role in the effector functions of
      polymorphonuclear neutrophils (PMN), we evaluated which FcR on PMN from gingival
      crevicular fluid (GCF) serves as an optimal target molecule for FcR-directed
      immunotherapy. GCF PMN and peripheral blood (PB) PMN from adult periodontitis
      patients were analyzed for their immunoglobulin G (IgG) and IgA FcR (Fc gamma R
      and Fc alpha R, respectively) expression and function by studying IgG- and IgA
      mediated elimination of P. gingivalis. GCF PMN exhibited higher Fc alpha RI and
      Fc gamma RI levels and lower Fc gamma RIIa and Fc gamma RIIIb levels than PB PMN.
      Functional studies revealed that GCF PMN exhibited less of a capacity to
      phagocytose and kill IgG1-opsonized P. gingivalis than PB PMN. IgA1-mediated
      phagocytosis and killing capacity was, however, comparable between GCF PMN and PB
      PMN. In summary, these in vitro results document that Fc alpha RI represents a
      candidate target for FcR-directed immunotherapy for the clearance of P.
      gingivalis.

PMID- 11292711
TI  - Interleukin-4 is essential for the control of microfilariae in murine infection
      with the filaria Litomosoides sigmodontis.
AB  - Litomosoides sigmodontis is the only filaria which develops from infective larvae
      into microfilaria-producing adults in immunocompetent laboratory mice. In this
      study we report that interleukin-4 knockout (IL-4 KO) mice have an up to 100-fold
      higher and a significantly prolonged microfilaremia compared to wild-type BALB/c
      mice, as well as 20 times more microfilariae in the thoracic cavity, the site of
      infection. While worm development and adult worm persistence were equivalent in
      IL-4 KO and wild-type mice, the fertility and length of adult female worms in IL
      4 KO mice was clearly enhanced. The high susceptibility to microfilariae in IL-4
      KO mice required the presence of adult worms in a full infection cycle since
      microfilariae loads did not differ much between IL-4 KO and wild-type mice when
      purified microfilariae were injected into mice. In addition, we found that
      eosinophilia was diminished and immunoglobulin E (IgE) was absent in IL-4 KO
      mice. IgE, however, does not seem to be the essential factor for microfilarial
      containment since microfilaremia was not elevated in B-cell KO mice. In
      conclusion, IL-4 is shown for the first time to be essential for the control of
      microfilarial loads but not of adult worm loads in a fully permissive murine
      filarial infection. IL-4 dependent effector pathways seem to operate on adult
      worms rather than directly on microfilariae.

PMID- 11292712
TI  - Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce
      immunomodulatory prostaglandins.
AB  - Enhanced prostaglandin production during fungal infection could be an important
      factor in promoting fungal colonization and chronic infection. Host cells are one
      source of prostaglandins; however, another potential source of prostaglandins is
      the fungal pathogen itself. Our objective was to determine if the pathogenic
      yeasts Cryptococcus neoformans and Candida albicans produce prostaglandins and,
      if so, to begin to define the role of these bioactive lipids in yeast biology and
      disease pathogenesis. C. neoformans and C. albicans both secreted prostaglandins
      de novo or via conversion of exogenous arachidonic acid. Treatment with
      cyclooxygenase inhibitors dramatically reduced the viability of the yeast and the
      production of prostaglandins, suggesting that an essential cyclooxygenase like
      enzyme may be responsible for fungal prostaglandin production. A PGE series lipid
      was purified from both C. albicans and C. neoformans and was biologically active
      on both fungal and mammalian cells. Fungal PGE(x) and synthetic PGE(2) enhanced
      the yeast-to-hypha transition in C. albicans. Furthermore, in mammalian cells,
      fungal PGE(x) down-modulated chemokine production, tumor necrosis factor alpha
      production, and splenocyte proliferation while up-regulating interleukin 10
      production. These are all activities previously documented for mammalian PGE(2).
      Thus, eicosanoids are produced by pathogenic fungi, are critical for growth of
      the fungi, and can modulate host immune functions. The discovery that pathogenic
      fungi produce and respond to immunomodulatory eicosanoids reveals a virulence
      mechanism that has potentially great implications for understanding the
      mechanisms of chronic fungal infection, immune deviation, and fungi as disease
      cofactors.

PMID- 11292713
TI  - Intranasal immunization enhances clearance of nontypeable Haemophilus influenzae
      and reduces stimulation of tumor necrosis factor alpha production in the murine
      model of otitis media.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing otitis
      media (OM). One of the outer membrane proteins of NTHi, P6, is a common antigen
      to all strains and is considered a candidate for mucosal vaccine. We have
      previously reported that intranasal immunization with P6 and cholera toxin (CT)
      could induce P6-specific immunoglobulin A (IgA) antibodies in the middle ear. In
      the present study, we assessed the effect of intranasal immunization for the
      protection against NTHi-induced OM. Mice were immunized intranasally with P6 and
      CT as an adjuvant on days 0, 7, and 14. Control mice were given phosphate
      buffered saline (PBS) without antigen. One week after the final immunization, a
      suspension of live NTHi (10(7) CFU) was injected into the tympanic cavity to
      induce experimental OM. On days 3 and 7 after bacterial challenge, mice were
      killed and middle ear effusions (MEEs) were collected. All immunized mice showed
      elevated titers of P6-specific antibodies in MEEs. The rank order of specific
      antibody included, from highest to lowest levels, IgG, IgA, and IgM. In addition,
      immunized mice showed enhanced clearance of NTHi from the middle ear and the
      number of NTHi in MEEs of immunized mice was reduced by 97% on day 3 and by 92%
      on day 7 after bacterial challenge relative the number in the MEEs of control
      mice. The protective effect of intranasal immunization on the incidence of NTHi
      induced experimental OM was evident on day 7 after challenge. By day 7, the
      number of MEEs in immunized mice was 64% less than that in control mice and the
      incidence of NTHi culture-positive MEEs in immunized mice was 56% less than that
      in control mice. Less stimulation of tumor necrosis factor alpha (TNF-alpha)
      production in the middle ear was evident on day 3 after challenge. Immunized mice
      showed lower concentrations of TNF-alpha in MEEs. These results indicate that
      intranasal immunization affords protection against experimental OM as evidenced
      by enhanced clearance of NTHi and less stimulation of TNF-alpha production in the
      middle ear. These findings suggest that a nasal vaccine might be useful for
      preventing OM.

PMID- 11292715
TI  - Cellular uptake of the Clostridium perfringens binary iota-toxin.
AB  - The binary iota-toxin is produced by Clostridium perfringens type E strains and
      consists of two separate proteins, the binding component iota b (98 kDa) and an
      actin-ADP-ribosylating enzyme component iota a (47 kDa). Iota b binds to the cell
      surface receptor and mediates the translocation of iota a into the cytosol. Here
      we studied the cellular uptake of iota-toxin into Vero cells. Bafilomycin A1, but
      not brefeldin A or nocodazole, inhibited the cytotoxic effects of iota-toxin,
      indicating that toxin is translocated from an endosomal compartment into the
      cytoplasm. Acidification (pH < or = 5.0) of the extracellular medium enabled iota
      a to directly enter the cytosol in the presence of iota b. Activation by
      chymotrypsin induced oligomerization of iota b in solution. An average mass of
      530 +/- 28 kDa for oligomers was determined by analytical ultracentrifugation,
      indicating heptamer formation. The entry of iota-toxin into polarized CaCo-2
      cells was studied by measuring the decrease in transepithelial resistance after
      toxin treatment. Iota-toxin led to a significant decrease in resistance when it
      was applied to the basolateral surface of the cells but not following application
      to the apical surface, indicating a polarized localization of the iota-toxin
      receptor.

PMID- 11292714
TI  - Specific antibodies to Porphyromonas gingivalis Lys-gingipain by DNA vaccination
      inhibit bacterial binding to hemoglobin and protect mice from infection.
AB  - Lys-gingipain (KGP), a lysine-specific cysteine proteinase, is one of the major
      virulence factors of Porphyromonas gingivalis. Here we examined the involvement
      of the catalytic domain of KGP (KGP(cd)) in hemoglobin binding by P. gingivalis,
      using a specific immunoglobulin G (IgG) elicited by the administration of plasmid
      DNA encoding KGP(cd) or the catalytic domain of Arg-gingipain (RGP(cd)). The
      pSeq2A/kgp(cd) and pSeq2B/rgp(cd) plasmids were constructed by the ligation of
      kgp(cd) and rgp(cd) DNA fragments, respectively. Female BALB/c mice were
      immunized with each of these plasmids. pSeq2A/kgp(cd) elicited a strong response
      to recombinant KGP(cd) (rKGP(cd)), as well as to comparably produced rRGP(cd)
      reactive antibodies. The serum antibodies elicited by pSecTag2B/rgp(cd) also
      cross-reacted with rKGP(cd) as well as rRGP(cd). Anti-KGP(cd) IgG significantly
      inhibited hemoglobin binding by P. gingivalis. Furthermore, the inhibition of
      hemoglobin binding was markedly enhanced by a combination of anti-KGP(cd) and
      anti-fimbriae. Anti-RGP(cd) IgG showed a negligible inhibitory effect, while both
      anti-KGP(cd) and anti-RGP(cd) IgGs showed significant inhibitory effects on Lys-
      and Arg-specific proteolytic activities and on the growth of P. gingivalis under
      iron-restricted conditions where supplemented hemoglobin was the sole iron
      source. Immunized mice were challenged by intraperitoneal inoculation with P.
      gingivalis. All nonimmunized mice died within 72 h; however, vaccination with
      pSeq2A/kgp(cd) and pSeq2B/rgp(cd) prevented inflammatory responses and prolonged
      the survival rate of immunized mice by 43 and 27%, respectively. These results
      suggest that KGP(cd) acts as a hemoglobin-binding protein and can also be useful
      as an immunogen inducing a protective response to P. gingivalis infection.

PMID- 11292716
TI  - Exacerbation of Acanthamoeba keratitis in animals treated with anti-macrophage
      inflammatory protein 2 or antineutrophil antibodies.
AB  - Neutrophils are thought to be involved in many infectious diseases and have been
      found in high numbers in the corneas of patients with Acanthamoeba keratitis.
      Using a Chinese hamster model of keratitis, conjunctival neutrophil migration was
      manipulated to determine the importance of neutrophils in this disease.
      Inhibition of neutrophil recruitment was achieved by subconjunctival injection
      with an antibody against macrophage inflammatory protein 2 (MIP-2), a powerful
      chemotactic factor for neutrophils which is secreted by the cornea. In other
      experiments, neutrophils were depleted by intraperitoneal injection of anti
      Chinese hamster neutrophil antibody. The inhibition of neutrophils to the cornea
      resulted in an earlier onset and more severe infection compared to controls. Anti
      MIP-2 antibody treatment produced an almost 35% reduction of myeloperoxidase
      activity in the cornea 6 days postinfection, while levels of endogenous MIP-2
      secretion increased significantly. Recruitment of neutrophils into the cornea via
      intrastromal injections of recombinant MIP-2 generated an initially intense
      inflammation that resulted in the rapid resolution of the corneal infection. The
      profound exacerbation of Acanthamoeba keratitis seen when neutrophil migration
      was inhibited, combined with the rapid clearing of the disease in the presence of
      increased neutrophils, strongly suggests that neutrophils play an important role
      in combating Acanthamoeba infections in the cornea.

PMID- 11292717
TI  - Subinhibitory clindamycin differentially inhibits transcription of exoprotein
      genes in Staphylococcus aureus.
AB  - It has long been known that certain antibiotics, at subinhibitory concentrations,
      differentially inhibit the synthesis of alpha-hemolysin and other staphylococcal
      virulence factors. In this report, we show that subinhibitory clindamycin (SBCL)
      eliminates production of nearly all exoproteins by Staphylococcus aureus but has
      virtually no effect on cytoplasmic proteins. The effect was abolished by a gene
      conferring resistance to macrolides-lincosamides-streptogramin B, showing that
      differential inhibition of protein synthesis is responsible; remarkably, however,
      subinhibitory clindamycin blocked production of several of the individual
      exoprotein genes, including spa (encoding protein A), hla (encoding alpha
      hemolysin), and spr (encoding serine protease), at the level of transcription,
      suggesting that the primary effect must be differential inhibition of the
      synthesis of one or more regulatory proteins. In contrast to earlier reports,
      however, we found that subinhibitory clindamycin stimulates synthesis of
      coagulase and fibronectin binding protein B, also at the level of transcription.
      agr and sar expression was minimally affected by subinhibitory clindamycin. These
      effects varied from strain to strain and do not seem to be responsible for the
      effects of subinhibitory clindamycin on the overall exoprotein pattern.

PMID- 11292718
TI  - In vivo-expressed genes of Pasteurella multocida.
AB  - Pasteurella multocida is the causative agent of infectious diseases of economic
      importance such as fowl cholera, bovine hemorrhagic septicemia, and porcine
      atrophic rhinitis. However, knowledge of the molecular mechanisms and
      determinants that P. multocida requires for virulence and pathogenicity is still
      limited. To address this issue, we developed a genetic expression system, based
      on the in vivo expression technology approach first described by Mahan et al.
      (Science 259:686--688, 1993), to identify in vivo-expressed genes of P.
      multocida. Numerous genes, such as those encoding outer membrane lipoproteins,
      metabolic and biosynthetic enzymes, and a number of hypothetical proteins, were
      identified. These may prove to be useful targets for attenuating mutation and/or
      warrant further investigation for their roles in immunity and/or pathogenesis.

PMID- 11292719
TI  - Expression of pls, a gene closely associated with the mecA gene of methicillin
      resistant Staphylococcus aureus, prevents bacterial adhesion in vitro.
AB  - The pls gene, coding for a large surface protein of methicillin-resistant
      Staphylococcus aureus, was cloned from a strain which adheres poorly to several
      mammalian proteins. The structure of pls revealed three distinct repeat regions,
      one of which was a serine-aspartate repeat characteristic of the Clf-Sdr family
      of surface proteins in staphylococci. The lengths of the repeat regions varied in
      different clinical strains and could be used as epidemiological markers. pls was
      found to be closely associated with the mecA gene by pulsed-field gel
      electrophoresis analysis of SmaI-digested DNA. A pls mutant constructed by allele
      replacement adhered well to immobilized fibronectin and immunoglobulin G, in
      contrast to the parental strain, suggesting that Pls could have a role in
      preventing adhesion at some stages during an infection.

PMID- 11292720
TI  - Flagellar phase variation of Salmonella enterica serovar Typhimurium contributes
      to virulence in the murine typhoid infection model but does not influence
      Salmonella-induced enteropathogenesis.
AB  - Although Salmonella enterica serovar Typhimurium can undergo phase variation to
      alternately express two different types of flagellin subunit proteins, FljB or
      FliC, no biological function for this phenomenon has been described. In this
      investigation, we constructed phase-locked derivatives of S. enterica serovar
      Typhimurium that expressed only FljB (termed locked-ON) or FliC (termed locked
      OFF). The role of phase variation in models of enteric and systemic pathogenesis
      was then evaluated. There were no differences between the wild-type parent strain
      and the two phase-locked derivatives in adherence and invasion of mouse
      epithelial cells in vitro, survival in mouse peritoneal macrophages, or in a
      bovine model of gastroenteritis. By contrast, the locked-OFF mutant was virulent
      in mice following oral or intravenous (i.v.) inoculation but the locked-ON mutant
      was attenuated. When these phase-locked mutants were compared in studies of i.v.
      kinetics in mice, similar numbers of the two strains were isolated from the blood
      and spleens of infected animals at 6 and 24 h. However, the locked-OFF mutant was
      recovered from the blood and spleens in significantly greater numbers than the
      locked-ON strain by day 2 of infection. By 5 days postinfection, a majority of
      the mice infected with the locked-OFF mutant had died compared with none of the
      mice infected with the locked-ON mutant. These results suggest that phase
      variation is not involved in the intestinal stage of infection but that once S.
      enterica serovar Typhimurium reaches the spleens of susceptible mice those
      organisms in the FliC phase can grow and/or survive better than those in the FljB
      phase. Additional experiments with wild-type S. enterica serovar Typhimurium,
      fully capable of switching flagellin type, supported this hypothesis. We conclude
      that organisms that have switched to the FliC(+) phase have a selective advantage
      in the mouse model of typhoid fever but have no such advantage in invasion of
      epithelial cells or the induction of enteropathogenesis.

PMID- 11292721
TI  - Increased immunogenicity and induction of class switching by conjugation of
      complement C3d to pneumococcal serotype 14 capsular polysaccharide.
AB  - Previous studies have demonstrated an adjuvant effect for the C3d fragment of
      complement C3 when coupled to T-dependent protein antigens. In this study, we
      examined the antibody response to covalent conjugates of C3d and a T-independent
      antigen, the capsular polysaccharide of serotype 14 Streptococcus pneumoniae
      (PPS14). We prepared a conjugate of mouse C3d and PPS14 and compared its
      immunogenicity with that of a conjugate of PPS14 and ovalbumin (OVA). When BALB/c
      mice were immunized with PPS14-C3d, there was a significant increase in serum
      anti-PPS14 concentrations compared with either native PPS14 or control PPS14
      glycine conjugates. This was accompanied by a switch in anti-PPS14 from
      predominantly immunoglobulin M (IgM) to IgG1 by day 25 following primary
      immunization. Following secondary immunization with PPS14-C3d, there was a marked
      booster response and a further increase in the ratio of IgG1 to IgM anti-PPS14.
      Although the primary antibody response to the PPS14-OVA conjugate exceeded that
      induced by immunization with PPS14-C3d, serum anti-PPS14 concentrations after a
      second injection of PPS14-C3d were nearly identical to those induced by secondary
      immunization with PPS14-OVA. Experiments with athymic nude mice suggested that T
      cells were not required for the adjuvant effect of C3d on the primary immune
      response to PPS14 but were necessary for enhancement of the memory response after
      a second injection of PPS14-C3d. These studies show that the adjuvant effects of
      C3d extend to T-independent antigens as well as T-dependent antigens. As a means
      of harnessing the adjuvant potential of the innate immune system, C3d conjugates
      may prove useful as a component of vaccines against encapsulated bacteria.

PMID- 11292722
TI  - Improved immunogenicity and protective efficacy of a tuberculosis DNA vaccine
      encoding Ag85 by protein boosting.
AB  - C57BL/6 mice were vaccinated with plasmid DNA encoding Ag85 from Mycobacterium
      tuberculosis, with Ag85 protein in adjuvant, or with a combined DNA prime-protein
      boost regimen. While DNA immunization, as previously described, induced robust
      Th1-type cytokine responses, protein-in-adjuvant vaccination elicited very poor
      cytokine responses, which were 10-fold lower than those observed with DNA
      immunization alone. Injection of Ag85 DNA-primed mice with 30 to 100 microg of
      purified Ag85 protein in adjuvant increased the interleukin-2 and gamma
      interferon (IFN-gamma) response in spleen two- to fourfold. Further,
      intracellular cytokine analysis by flow cytometry also showed an increase in IFN
      gamma-producing CD4(+) T cells in DNA-primed-protein-boosted animals, compared to
      those that received only the DNA vaccination. Moreover, these responses appeared
      to be better sustained over time. Antibodies were readily produced by all three
      methods of immunization but were exclusively of the immunoglobulin G1 (IgG1)
      isotype following protein immunization in adjuvant and preferentially of the
      IgG2a isotype following DNA and DNA prime-protein boost vaccination. Finally,
      protein boosting increased the protective efficacy of the DNA vaccine against an
      intravenous M. tuberculosis H37Rv challenge infection, as measured by CFU or
      relative light unit counts in lungs 1 and 2 months after infection. The capacity
      of exogenously given protein to boost the DNA-primed vaccination effect
      underlines the dominant role of Th1-type CD4(+) helper T cells in mediating
      protection.

PMID- 11292723
TI  - Porphyromonas gingivalis gingipains and adhesion to epithelial cells.
AB  - Porphyromonas gingivalis is one of the principal organisms associated with adult
      periodontitis. Bacterial surface proteins such as fimbriae and gingipain
      hemagglutinin domains have been implicated as adhesins that actuate colonization
      of epithelium lining the gingival sulcus. We investigated the genetics of P.
      gingivalis adhesion to monolayers of epithelial cells using wild-type and
      gingipain mutant strains. These experiments suggested that arginine-specific
      gingipain (Rgp) catalytic activity modulated adhesion. From the data obtained
      with rgp mutants, we constructed a working hypothesis predicting that attachment
      and detachment of P. gingivalis to epithelial cells were mediated by gingipain
      adhesin and Rgp catalytic domains, respectively. A membrane-based epithelial cell
      binding assay, used to locate adhesins in extracellular fractions of wild-type
      and mutant strains, recognized gingipain peptides as adhesins rather than
      fimbriae. We developed a capture assay that demonstrated the binding of gingipain
      adhesin peptides to oral epithelial cells. The adherence of fimbrillin to
      epithelial cells was detected after heat denaturation of cell fractions. The
      prediction that Rgp catalytic activities mediated detachment was substantiated
      when the high level of attachment of an rgp mutant was reduced in the presence of
      wild-type cell fractions that contained gingipain catalytic activities.

PMID- 11292724
TI  - Antigenic variation of Anaplasma marginale: major surface protein 2 diversity
      during cyclic transmission between ticks and cattle.
AB  - The rickettsial pathogen Anaplasma marginale expresses a variable immunodominant
      outer membrane protein, major surface protein 2 (MSP2), involved in antigenic
      variation and long-term persistence of the organism in carrier animals. MSP2
      contains a central hypervariable region of about 100 amino acids that encodes
      immunogenic B-cell epitopes that induce variant-specific antibodies during
      infection. Previously, we have shown that MSP2 is encoded on a polycistronic mRNA
      transcript in erythrocyte stages of A. marginale and defined the structure of the
      genomic expression site for this transcript. In this study, we show that the same
      expression site is utilized in stages of A. marginale infecting tick salivary
      glands. We also analyzed the variability of this genomic expression site in
      Oklahoma strain A. marginale transmitted from in vitro cultures to cattle and
      between cattle and ticks. The structure of the expression site and flanking
      regions was conserved except for sequence that encoded the MSP2 hypervariable
      region. At least three different MSP2 variants were encoded in each A. marginale
      population. The major sequence variants did not change on passage of A. marginale
      between culture, acute erythrocyte stage infections, and tick salivary glands but
      did change during persistent infections of cattle. The variant types found in
      tick salivary glands most closely resembled those present in bovine blood at the
      time of acquisition of infection, whether infection was acquired from an acute or
      from a persistent rickettsemia. These variations in structure of an expression
      site for a major, immunoprotective outer membrane protein have important
      implications for vaccine development and for obtaining an improved understanding
      of the mechanisms of persistence of ehrlichial infections in humans, domestic
      animals, and reservoir hosts.

PMID- 11292726
TI  - Reversal of the CD4(+)/CD8(+) T-cell ratio in lymph node cells upon in vitro
      mitogenic stimulation by highly purified, water-soluble S3-S4 dimer of pertussis
      toxin.
AB  - Pertussis toxin (PT), a holomer consisting of a catalytic S1 subunit and a B
      oligomer composed of S2-S4 and S3-S4 dimers, held together by the S5 subunit,
      exerts profound effects on immune cells, including T-cell mitogenicity. While the
      mitogenic activity of PT was shown to reside fully within the B oligomer, it
      could not be assigned to any particular B-oligomer component. In this study, we
      purified the S3-S4 dimer to homogeneity under conditions propitious to
      maintenance of the native conformation. In contrast to previous reports which
      suggested that both S3-S4 and S2-S4 dimers are necessary for mitogenic activity,
      our preparation of the highly purified S3-S4 dimer was as strongly mitogenic as
      the B oligomer, suggesting that the S3-S4 dimer accounts for the mitogenic
      activity of the B oligomer. Moreover, in vitro stimulation of naive lymphocytes
      by the S3-S4 dimer resulted in reversal of the normal CD4(+)/CD8(+) T-cell ratio
      from approximately 2:1 to 1:2. The reversal of the CD4(+)/CD8(+) T-cell ratio is
      unlikely to be due to preferential apoptosis-necrosis of CD4(+) T cells, as
      indicated by fluorescence-activated cell sorter analysis of annexin-stained T
      cell subsets, or to preferential stimulation of CD8(+) T cells. The mechanism
      underlying the reversal requires further investigation. Nevertheless, the data
      presented indicate that the S3-S4 dimer may have potential use in the context of
      diseases amenable to immunological modulation.

PMID- 11292725
TI  - BrkA protein of Bordetella pertussis inhibits the classical pathway of complement
      after C1 deposition.
AB  - Bordetella pertussis produces a 73-kDa protein, BrkA (Bordetella resistance to
      killing), which inhibits the bactericidal activity of complement. In this study
      we characterized the step in the complement cascade where BrkA acts, using three
      strains: a wild-type strain, a strain containing an insertional disruption of
      brkA, and a strain containing two copies of the brkA locus. Following incubation
      with 10% human serum, killing was greatest for the BrkA mutant, followed by that
      for the wild-type strain, while the strain with two copies of brkA was the most
      resistant. Complement activation was monitored by enzyme-linked immunosorbent
      assay (ELISA) or Western blotting. ELISAs for SC5b-9, the soluble membrane attack
      complex, showed that production of SC5b-9 was greatest with the brkA mutant, less
      with the wild type, and least with the strain containing two copies of brkA.
      Deposition of complement proteins on the bacteria was monitored by Western
      blotting. A decrease in deposition on the bacteria of C4, C3, and C9 corresponded
      with decreased complement sensitivity. Deposition of C1, however, was not
      affected by the presence of BrkA. These studies show that BrkA inhibits the
      classical pathway of complement activation and prevents accumulation of deposited
      C4.

PMID- 11292727
TI  - Chlamydia pneumoniae major outer membrane protein is a surface-exposed antigen
      that elicits antibodies primarily directed against conformation-dependent
      determinants.
AB  - The major outer membrane protein (MOMP) of Chlamydia trachomatis serovariants is
      known to be an immunodominant surface antigen. Moreover, it is known that the C.
      trachomatis MOMP elicits antibodies that recognize both linear and conformational
      antigenic determinants. In contrast, it has been reported that the MOMP of
      Chlamydia pneumoniae is not surface exposed and is immunorecessive. We
      hypothesized that the discrepancies between C. trachomatis and C. pneumoniae MOMP
      exposure on intact chlamydiae and immunogenic properties might be because the
      focus of the host's immune response is directed to conformational epitopes of the
      C. pneumoniae MOMP. We therefore conducted studies aimed at defining the surface
      exposure of MOMP and the conformational dominance of MOMP antibodies. We present
      here a description of C. pneumoniae species-specific monoclonal antibody (MAb),
      GZD1E8, which recognizes a conformational epitope on the surface of C.
      pneumoniae. This MAb is potent in the neutralization of C. pneumoniae infectivity
      in vitro. Another previously described C. pneumoniae species-specific monoclonal
      antibody, RR-402, displayed very similar characteristics. However, the antigenic
      determinant recognized by RR-402 has yet to be identified. We show by
      immunoprecipitation of C. pneumoniae with GZD1E8 and RR-402 MAbs and by mass
      spectrometry analysis of immunoprecipitated proteins that both antibodies GZD1E8
      and RR-402 recognize the MOMP of C. pneumoniae and that this protein is localized
      on the surface of the organism. We also show that human sera from C. pneumoniae
      positive donors consistently recognize the MOMP by immunoprecipitation,
      indicating that the MOMP of C. pneumoniae is an immunogenic protein. These
      findings have potential implications for both C. pneumoniae vaccine and
      diagnostic assay development.

PMID- 11292728
TI  - Salmonella enterica serovar-host specificity does not correlate with the
      magnitude of intestinal invasion in sheep.
AB  - The colonization of intestinal and systemic tissues by Salmonella enterica
      serovars with different host specificities was determined 7 days after
      inoculation of 1 to 2-month-old lambs. Following oral inoculation, S. enterica
      serovars Abortusovis, Dublin, and Gallinarum were recovered in comparable numbers
      from the intestinal mucosa, but serovar Gallinarum was recovered in lower numbers
      than the other serovars from systemic sites. The pattern of bacterial recovery
      from systemic sites following intravenous inoculation was similar. The magnitude
      of intestinal invasion was evaluated in ovine ligated ileal loops in vivo.
      Serovars Dublin and Gallinarum and the broad-host-range Salmonella serovar
      Typhimurium were recovered in comparable numbers from ileal mucosa 3 h after loop
      inoculation, whereas the recovery of serovar Abortusovis was approximately 10
      fold lower. Microscopic analysis of intestinal mucosae infected with serovars
      Typhimurium and Dublin showed dramatic morphological changes and infiltration of
      inflammatory cells, whereas mucosae infected with serovars Abortusovis and
      Gallinarum were indistinguishable from uninfected mucosae. Together these data
      suggest that Salmonella serovar specificity in sheep correlates with bacterial
      persistence at systemic sites. Intestinal invasion and avoidance of the host's
      intestinal inflammatory response may contribute to but do not determine the
      specificity of serovar Abortosovis for sheep. Intestinal invasion by serovar
      Abortusovis was significantly reduced after mutation of invH but was not reduced
      following curing of the virulence plasmid, suggesting that the Salmonella
      pathogenicity island 1 influences but the virulence plasmid genes do not
      influence the ability of serovar Abortusovis to invade the intestinal mucosa in
      sheep.

PMID- 11292729
TI  - Antibodies against listerial protein 60 act as an opsonin for phagocytosis of
      Listeria monocytogenes by human dendritic cells.
AB  - Human-monocyte-derived dendritic cells (MoDC) are very efficient in the uptake of
      Listeria monocytogenes, a gram-positive bacterium which is an important pathogen
      in humans and animals causing systemic infections with symptoms such as
      septicemia and meningitis. In this work, we analyzed the influence of blood
      plasma on the internalization of L. monocytogenes into human MoDC and compared
      the uptake of L. monocytogenes with that of Salmonella enterica serovar
      Typhimurium and Yersinia enterocolitica. While human plasma did not significantly
      influence the uptake of serovar Typhimurium and Y. enterocolitica by human MoDC,
      the efficiency of the uptake of L. monocytogenes by these phagocytes was strongly
      enhanced by human plasma. In plasma-free medium the internalization of L.
      monocytogenes was very low, whereas the addition of pooled human immunoglobulins
      resulted in the internalization of these bacteria to a degree comparable to the
      highly efficient uptake observed with human plasma. All human plasma tested
      contained antibodies against the 60-kDa extracellular protein of L. monocytogenes
      (p60), and anti-p60 antibodies were also found in the commercially available
      pooled immunoglobulins. Strikingly, in contrast to L. monocytogenes wild type, an
      iap deletion mutant (totally deficient in p60) showed only a minor difference in
      the uptake by human MoDC in the presence or the absence of human plasma. These
      results support the assumption that antibodies against the listerial p60 protein
      may play an important role in Fc-receptor-mediated uptake of L. monocytogenes by
      human MoDC via opsonization of the bacteria. This process may have a major impact
      in preventing systemic infection in L. monocytogenes in immunocompetent humans.

PMID- 11292730
TI  - Stable transfection of the bovine NRAMP1 gene into murine RAW264.7 cells: effect
      on Brucella abortus survival.
AB  - Genetically based natural resistance to brucellosis in cattle provides for novel
      strategies to control zoonotic diseases. Bovine NRAMP1, the homologue of a murine
      gene (Bcg), has been identified as a major candidate for controlling the in vivo
      resistant phenotype. We developed an in vitro model for expression of resistance-
      and susceptibility-associated alleles of bovine NRAMP1 as stable transgenes under
      the regulatory control of the bovine NRAMP1 promoter in the murine RAW264.7
      macrophage cell line (Bcg(s)) to analyze the regulation of the NRAMP1 gene and
      its role in macrophage function. We demonstrated that the 5'-flanking region of
      bovine NRAMP1, despite the lack of TATA and CAAT boxes, has a functional promoter
      capable of driving the expression of a transgene in murine macrophages. A
      polymorphism within a microsatellite in the 3' untranslated region critically
      affects the expression of bovine NRAMP1 and the control of in vitro replication
      of Brucella abortus but not Salmonella enterica serovar Dublin. We did not
      observe any differences in the production of NO by resting or gamma interferon
      (IFN-gamma)- and IFN-gamma-lipopolysaccharide (LPS)-treated transfected cell
      lines, yet the resistant transfected cell lines produced significantly less NO
      than other cell lines, following stimulation with LPS at 24 and 48 h.

PMID- 11292731
TI  - Clumping factor A mediates binding of Staphylococcus aureus to human platelets.
AB  - The direct binding of bacteria to platelets may be an important virulence
      mechanism in the pathogenesis of infective endocarditis. We have previously
      described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain
      ISP479, with reduced ability to bind human platelets in vitro. When tested in an
      animal model of endocarditis, the PS12 strain was less virulent than its parental
      strain, as measured by bacterial densities in endocardial vegetations and
      incidence of systemic embolization. We have now characterized the gene disrupted
      in PS12 and its function in platelet binding. DNA sequencing, Southern blotting,
      and PCR analysis indicate that PS12 contained two Tn551 insertions within the
      clumping factor A (ClfA) locus (clfA). The first copy was upstream from the clfA
      start codon and appeared to have no effect on ClfA production. The second
      insertion was within the region encoding the serine aspartate repeat of ClfA and
      resulted in the production of a truncated ClfA protein that was secreted from the
      cell. A purified, recombinant form of the ClfA A region, encompassing amino acids
      40 through 559, significantly reduced the binding of ISP479C to human platelets
      by 44% (P = 0.0001). Immunoprecipitation of recombinant ClfA that had been
      incubated with solubilized platelet membranes coprecipitated a 118-kDa platelet
      membrane protein. This protein does not appear to be glycoprotein IIb. These
      results indicate that platelet binding by S. aureus is mediated in part by the
      direct binding of ClfA to a novel 118-kDa platelet membrane receptor.

PMID- 11292732
TI  - Protective efficacy of H antigen from Histoplasma capsulatum in a murine model of
      pulmonary histoplasmosis.
AB  - We previously reported that immunization with H antigen from Histoplasma
      capsulatum did not protect mice against an intravenous challenge with yeasts.
      Here, we investigated the utility of H antigen to protect mice in a model of
      pulmonary histoplasmosis. Mice immunized with H antigen and challenged
      intranasally 4 weeks postvaccination were protected against sublethal and lethal
      challenges with H. capsulatum yeasts. If the challenge was performed 3 months
      after vaccination, there was a reduction in fungal burden following sublethal
      challenge and a modest delay in mortality in mice given a lethal inoculum.
      Vaccination was associated with production of gamma interferon, granulocyte
      macrophage colony-stimulating factor, interleukin-4, and interleukin-10 by
      splenocytes. Vaccination with H antigen was not accompanied by a major expansion
      of CD4(+) or CD8(+) cells in spleens of mice. These results demonstrate that H
      antigen may be useful as a protective immunogen against pulmonary exposure to H.
      capsulatum.

PMID- 11292733
TI  - Passive transfer of immunoglobulin Y antibody to Streptococcus mutans glucan
      binding protein B can confer protection against experimental dental caries.
AB  - Active immunization with Streptococcus mutans glucan binding protein B (GBP-B)
      has been shown to induce protection against experimental dental caries. This
      protection presumably results from continuous secretion of salivary antibody to
      GBP-B, which inhibits accumulation of S. mutans within the oral biofilm. The
      purpose of this study was to explore the influence of short-term (9- or 24-day)
      passive oral administration of antibody to S. mutans GBP-B on the longer-term
      accumulation and cariogenicity of S. mutans in a rat model of dental caries.
      Preimmune chicken egg yolk immunoglobulin Y (IgY) or IgY antibody to S. mutans
      GBP-B was supplied in lower (experiment 1) and higher (experiment 2)
      concentrations in the diet and drinking water of rats for 9 (experiment 1) or 24
      (experiment 2) days. During the first 3 days of IgY feeding, all animals were
      challenged with 5 x 10(6) streptomycin-resistant S. mutans strain SJ-r organisms.
      Rats remained infected with S. mutans for 78 days, during which rat molars were
      sampled for the accumulation of S. mutans SJ-r bacteria and total streptococci.
      Geometric mean levels of S. mutans SJ-r accumulation on molar surfaces were
      significantly lower in antibody-treated rats on days 16 and 78 of experiment 2
      and were lower on all but the initial (day 5) swabbing occasions in both
      experiments. Relative to controls, the extent of molar dental caries measured on
      day 78 was also significantly decreased. The decrease in molar caries correlated
      with the amount and duration of antibody administration. This is the first
      demonstration that passive antibody to S. mutans GBP-B can have a protective
      effect against cariogenic S. mutans infection and disease. Furthermore, this
      decrease in infection and disease did not require continuous antibody
      administration for the duration of the infection period. This study also
      indicates that antibody to components putatively involved only in cellular
      aggregation can have a significant effect on the incorporation of mutans
      streptococci in dental biofilm.

PMID- 11292734
TI  - Activation of extracellular signal-related protein kinases 1 and 2 of the mitogen
      activated protein kinase family by lipopolysaccharide requires plasma in
      neutrophils from adults and newborns.
AB  - Neutrophils exposed to low concentrations of gram-negative lipopolysaccharide
      (LPS) become primed and have an increased oxidative response to a second stimulus
      (e.g., formyl-methionyl-leucyl-phenylalanine [fMLP]). In studies aimed at
      understanding newborn sepsis, we have shown that neutrophils of newborns are not
      primed in response to LPS. To further understand the processes involved in LPS
      mediated priming of neutrophils, we explored the role of extracellular signal
      related protein kinases (ERK 1 and 2) of the mitogen-activated protein kinase
      family. We found that LPS activated ERK 1 and 2 in cells of both adults and
      newborns and that activation was plasma dependent (maximal at > or =5%) through
      LPS-binding protein. Although fibronectin in plasma is required for LPS-mediated
      priming of neutrophils of adults assessed by fMLP-triggered oxidative burst, it
      was not required for LPS-mediated activation of ERK 1 and 2. LPS-mediated
      activation was dose and time dependent; maximal activation occurred with
      approximately 5 ng of LPS per ml and at 10 to 40 min. We used the inhibitor PD
      98059 to study the role of ERK 1 and 2 in the LPS-primed fMLP-triggered oxidative
      burst. While Western blotting showed that 100 microM PD 98059 completely
      inhibited LPS-mediated ERK activation, oxidative response to fMLP by a
      chemiluminescence assay revealed that the same concentration inhibited the LPS
      primed oxidative burst by only 40%. We conclude that in neutrophils, LPS-mediated
      activation of ERK 1 and 2 requires plasma and that this activation is not
      dependent on fibronectin. In addition, we found that the ERK pathway is not
      responsible for the lack of LPS priming in neutrophils of newborns but may be
      required for 40% of the LPS-primed fMLP-triggered oxidative burst in cells of
      adults.

PMID- 11292735
TI  - Attenuated Shigella flexneri 2a Delta guaBA strain CVD 1204 expressing
      enterotoxigenic Escherichia coli (ETEC) CS2 and CS3 fimbriae as a live mucosal
      vaccine against Shigella and ETEC infection.
AB  - To construct a prototype hybrid vaccine against Shigella and enterotoxigenic
      Escherichia coli (ETEC), the genes encoding the production of ETEC CS2 and CS3
      fimbriae were isolated and expressed in attenuated Shigella flexneri 2a guaBA
      strain CVD 1204. The CS2 cotA to -D genes, isolated from ETEC strain C91F, and
      the CS3 cstA to -H genes, subcloned from plasmid pCS100, were cloned into ~15
      copy-number-stabilized pGA1 behind the osmotically regulated ompC promoter,
      resulting in high expression of both fimbriae. Under nonselective in vitro growth
      conditions, pGA1-CS2 and pGA1-CS3 were stable in CVD 1204, exhibiting a plasmid
      loss of only approximately 1% per duplication. Expression of CS2 and CS3 reduced
      the invasiveness of Shigella for HeLa cells and slowed the intracellular growth
      rate. Guinea pigs immunized intranasally with CVD 1204(pGA1-CS2) or CVD 1204(pGA1
      CS3), or with a mixture of these strains, developed secretory immunoglobulin A
      (IgA) in tears and serum IgG antibodies against Shigella lipopolysaccharide, CS2,
      and CS3 antigens. Moreover, the animals were protected against
      keratoconjunctivitis following conjunctival challenge with virulent S. flexneri
      2a strain 2457T. Animals immunized with Shigella expressing CS2 or CS3 developed
      serum antibodies that agglutinated Shigella as well as an ETEC strain bearing the
      homologous fimbriae, whereas animals immunized with combined CVD 1204(pGA1-CS2)
      and CVD 1204(pGA1-CS3) developed antibodies that agglutinated all three test
      strains. These observations support the feasibility of a multivalent vaccine
      against shigellosis and ETEC diarrhea consisting of multiple Shigella live
      vectors expressing relevant ETEC antigens.

PMID- 11292736
TI  - Comparison of the fibronectin-binding protein FNE from Streptococcus equi
      subspecies equi with FNZ from S. equi subspecies zooepidemicus reveals a major
      and conserved difference.
AB  - The gene fnz from Streptococcus equi subspecies zooepidemicus encodes a cell
      surface protein that binds fibronectin (Fn). Fifty tested isolates of S. equi
      subspecies equi all contain DNA sequences with similarity to fnz. This work
      describes the cloning and sequencing of a gene, designated fne, with similarity
      to fnz from two S. equi subspecies equi isolates. The DNA sequences were found to
      be identical in the two strains, and sequence comparison of the fne and fnz genes
      revealed only minor differences. However, one base deletion was found in the
      middle of the fne gene and eight base pairs downstream of the altered reading
      frame there is a stop codon. An Fn-binding protein was purified from the growth
      medium of a subspecies equi culture. Determination of the NH(2)-terminal amino
      acid sequence and molecular mass, as judged by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, revealed that the purified protein is the
      gene product of the 5'-terminal half of fne. Fn-binding activity has earlier only
      been found in the COOH-terminal half of FNZ. By the use of a purified recombinant
      protein containing the NH(2) half of FNZ, we provide here evidence that this half
      of the protein also harbors an Fn-binding domain.

PMID- 11292737
TI  - Disruption of the genes for ClpXP protease in Salmonella enterica serovar
      Typhimurium results in persistent infection in mice, and development of
      persistence requires endogenous gamma interferon and tumor necrosis factor alpha.
AB  - The enteric pathogen Salmonella enterica serovar Typhimurium, similar to other
      facultative intracellular pathogens, has been shown to respond to the hostile
      conditions inside macrophages of the host organism by producing a set of stress
      proteins that are also induced by various environmental stresses. The stress
      induced ClpXP protease is a member of the ATP-dependent proteases, which are
      known to be responsible for more than 90% of all proteolysis in Escherichia coli.
      To investigate the contribution of the ClpXP protease to the virulence of serovar
      Typhimurium we initially cloned the clpP and clpX operon from the pathogenic
      strain serovar Typhimurium chi3306 and then created insertional mutations in the
      clpP and/or clpX gene. The Delta clpP and Delta clpX mutants were used to
      inoculate BALB/c mice by either the intraperitoneal or the oral route and found
      to be limited in their ability to colonize organs of the lymphatic system and to
      cause systemic disease in the host. A variety of experiments were performed to
      determine the possible reasons for the loss of virulence. An oxygen-dependent
      killing assay using hydrogen peroxide and paraquat (a superoxide anion generator)
      and a serum killing assay using murine serum demonstrated that all of the serovar
      Typhimurium Delta clpP and Delta clpX mutants were as resistant to these killing
      mechanisms as the wild-type strain. On the other hand, the macrophage survival
      assay revealed that all these mutants were more sensitive to the intracellular
      environment than the wild-type strain and were unable to grow or survive within
      peritoneal macrophages of BALB/c mice. In addition, it was revealed that the
      serovar Typhimurium ClpXP-depleted mutant was not completely cleared but found to
      persist at low levels within spleens and livers of mice. Interferon gamma
      deficient mice and tumor necrosis factor alpha-deficient mice failed to survive
      the attenuated serovar Typhimurium infections, suggesting that both endogenous
      cytokines are essential for regulation of persistent infection with serovar
      Typhimurium.

PMID- 11292738
TI  - Extensive Mycobacterium bovis BCG infection of liver parenchymal cells in
      immunocompromised mice.
AB  - A histologic study was performed on the livers of wild-type (WT), severe combined
      immunodeficient (SCID), hydrocortisone acetate (HC)-treated WT, and HC-treated
      SCID mice infected intravenously with 10(5) CFU of Mycobacterium bovis BCG. It
      was found that infection progressed faster in SCID mice than in WT mice and that
      HC treatment caused exacerbation of infection in both types of mice. In all cases
      infection in the liver was confined to granulomas that were populated
      predominantly by macrophages. Higher levels of infection in HC-treated SCID mice,
      but not HC-treated WT mice, were associated with extensive infection and
      destruction of parenchymal cells at the margins of granulomas. The results
      indicate that in the absence of T-cell-mediated immunity and of HC-sensitive T
      cell-independent defense mechanisms, macrophages are incapable of restricting BCG
      growth and of confining infection to their cytoplasm. Consequently, BCG bacilli
      are released into the extracellular environment, where they are ingested by
      neighboring parenchymal cells.

PMID- 11292741
TI  - Interleukin-10 regulates the tissue factor activity of monocytes in an in vitro
      model of bacterial endocarditis.
AB  - Monocytes are important effector cells in the pathogenesis of bacterial
      endocarditis since they provide the tissue factor that activates the coagulation
      system and maintains established vegetations. Monocytes secrete cytokines that
      can modulate monocyte tissue factor activity (TFA), thereby affecting the
      formation and maintenance of vegetations. In this study, we show that monocytes
      cultured for 4 h on a Streptococcus sanguis-infected fibrin matrix mimicking the
      in vivo vegetational surface express high levels of TFA. This was accompanied by
      secretion of the proinflammatory cytokines tumor necrosis factor alpha (TNF
      alpha), interleukin-1 alpha (IL-1 alpha), and IL-1 beta. After a 24-h incubation
      period the anti-inflammatory cytokine IL-10 could also be detected. Our data show
      that, whereas TNF-alpha and IL-1 have a minor role in the induction of TFA by
      monocytes cultured on a fibrin matrix, TNF-alpha but not IL-1 plays an important
      role in the induction of IL-10 by these cells. In turn, our data show that IL-10
      is an important factor in the downregulation of monocyte TFA. In summary, we
      conclude that IL-10 is an important factor in the control of monocyte TFA in
      endocardial vegetations.

PMID- 11292739
TI  - Apoptotic signaling pathway activated by Helicobacter pylori infection and
      increase of apoptosis-inducing activity under serum-starved conditions.
AB  - The enhanced gastric epithelial cell apoptosis observed during infection with
      Helicobacter pylori has been suggested to be of significance in the etiology of
      gastritis, peptic ulcers, and neoplasia. To investigate the cell death signaling
      induced by H. pylori infection, human gastric epithelial cells were incubated
      with H. pylori for up to 72 h. H. pylori infection induced the activation of
      caspase -8, -9, and -3 and the expression of the proapoptotic Bcl-2 family
      proteins Bad and Bid. The peak of the activity of the caspases occurred at 24 h.
      At this time, the inhibition of caspase-8 or -9 almost completely suppressed H.
      pylori-induced apoptosis. Inhibition of caspase-8 suppressed the expression of
      Bad and Bid and the subsequent activation of caspase-9 and -3. These observations
      indicate that H. pylori induces apoptosis through a pathway involving the
      sequential induction of apical caspase-8 activity, the proapoptotic proteins Bad
      and Bid, caspase-9 activity, and effector caspase-3 activity. Activation of the
      pathway was independent of CagA or vacuolating toxin. A membrane fraction of H.
      pylori was sufficient to activate this pathway, and treatment with proteinase K
      eliminated the activity. Apoptotic activity of the membrane fraction was
      significantly increased by incubating the bacteria under serum-starved conditions
      for 24 h. These observations suggest that environmental conditions in the human
      stomach could induce H. pylori-mediated pathogenesis, leading to a variety of
      clinical outcomes.

PMID- 11292740
TI  - Perturbation and proinflammatory type activation of V delta 1(+) gamma delta T
      cells in African children with Plasmodium falciparum malaria.
AB  - gamma delta T cells have variously been implicated in the protection against, and
      the pathogenesis of, malaria, but few studies have examined the gamma delta T
      cell response to malaria in African children, who suffer the large majority of
      malaria-associated morbidity and mortality. This is unfortunate, since available
      data suggest that simple extrapolation of conclusions drawn from studies of
      nonimmune adults ex vivo and in vitro is not always possible. Here we show that
      both the frequencies and the absolute numbers of gamma delta T cells are
      transiently increased following treatment of Plasmodium falciparum malaria in
      Ghanaian children and they can constitute 30 to 50% of all T cells shortly after
      initiation of antimalarial chemotherapy. The bulk of the gamma delta T cells
      involved in this perturbation expressed V delta 1 and had a highly activated
      phenotype. Analysis of the T-cell receptors (TCR) of the V delta 1(+) cell
      population at the peak of their increase showed that all expressed V gamma chains
      were used, and CDR3 length polymorphism indicated that the expanded V delta 1
      population was highly polyclonal. A very high proportion of the V delta 1(+) T
      cells produced gamma interferon, while fewer V delta 1(+) cells than the average
      proportion of all CD3(+) cells produced tumor necrosis factor alpha. No
      interleukin 10 production was detected among TCR-gamma delta(+) cells in general
      or V delta 1(+) cells in particular. Taken together, our data point to an
      immunoregulatory role of the expanded V delta 1(+) T-cell population in this
      group of semi-immune P. falciparum malaria patients.

PMID- 11292742
TI  - Functional opsonic activity of human serum antibodies to inner core
      lipopolysaccharide (galE) of serogroup B meningococci measured by flow cytometry.
AB  - A recently described flow cytometric opsonophagocytic assay (OPA) was adapted to
      quantify the functional activity of serum antibodies specifically directed
      against serogroup B inner core lipopolysaccharide (LPS) of Neisseria
      meningitidis. The percentage of human peripheral polymorphonuclear leukocytes and
      monocytes (PMNms) ingesting fluorescently labeled, ethanol-fixed N. meningitidis
      organisms (phagocytic activity) in the presence of human sera was measured to
      reflect the serum opsonic activity against the bacterium. The contribution to
      opsonophagocytic activity of antibodies to inner core LPS was estimated by
      comparing the opsonic activities of adult and infant sera before and after
      adsorbing anti-LPS antibodies from the sera using purified LPS extracted from an
      LPS mutant (galE) of N. meningitidis strain MC58 (B:15:P1.7,16:L3). The
      specificity of the assay was further investigated using monoclonal antibody (MAb)
      B5, which binds to an inner core LPS epitope of N. meningitidis. A dose-dependent
      decrease in phagocytic activity was observed when MAb B5 was incubated with LPS
      from an inner core LPS (galE) mutant. Similarly, the number of PMNms ingesting
      fluorescently labeled polystyrene beads coated with inner core (galE) LPS
      decreased in a dose-dependent fashion when MAb B5 was incubated with various
      concentrations of the homologous inner core LPS. Strong correlations were found
      between the concentration of serum antibodies to inner core LPS (galE) versus the
      phagocytic activity using healthy adult sera (r(2) = 0.89). There was a
      correlation between phagocytic ingestion and initiation of intracellular
      oxidative burst (r(2) = 0.99) using polystyrene beads coated with inner core LPS
      and opsonized with the same sera using the oxidative burst indicator system
      dihydrorhodamine123/rhodamine 123. OPA results were also found to correlate
      closely with the results of the serum bactericidal assay using MAb B5 against the
      N. meningitidis MC58 galE mutant in the presence of human complement (r(2) =
      0.994, P = 0.003, two-tailed test). These studies demonstrate that functional
      antibodies are produced in humans against meningococcal inner core LPS and that
      the OPA is a useful approach to study the opsonic activity of antibodies to inner
      core LPS in health and disease.

PMID- 11292743
TI  - Down-regulation of glycosylphosphatidylinositol-specific phospholipase D induced
      by lipopolysaccharide and oxidative stress in the murine monocyte- macrophage
      cell line RAW 264.7.
AB  - Serum glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) activity is
      reduced over 75% in systemic inflammatory response syndrome. To investigate the
      mechanism of this response, expression of the GPI-PLD gene was studied in the
      mouse monocyte-macrophage cell line RAW 264.7 stimulated with lipopolysaccharide
      (LPS; 0.5 to 50 ng/ml). GPI-PLD mRNA was reduced approximately 60% in a time- and
      dose-dependent manner. Oxidative stress induced by 0.5 mM H(2)O(2) or 50 microM
      menadione also caused a greater than 50% reduction in GPI-PLD mRNA. The
      antioxidant N-acetyl-L-cysteine attenuated the down-regulatory effect of H(2)O(2)
      but not of LPS. Cotreatment of the cells with actinomycin D inhibited down
      regulation induced by either LPS or H(2)O(2). The half-life of GPI-PLD mRNA was
      not affected by LPS, or decreased slightly with H(2)O(2), indicating that the
      reduction in GPI-PLD mRNA is due primarily to transcriptional regulation.
      Stimulation with tumor necrosis factor alpha (TNF-alpha) resulted in
      approximately 40% reduction in GPI-PLD mRNA in human A549 alveolar carcinoma
      cells but not RAW 264.7 cells, suggesting that alternative pathways could exist
      in different cell types for down-regulating GPI-PLD expression during an
      inflammatory response and the TNF-alpha autocrine signaling mechanism alone is
      not sufficient to recapitulate the LPS-induced reduction of GPI-PLD in
      macrophages. Sublines of RAW 264.7 cells with reduced GPI-PLD expression
      exhibited increased cell sensitivity to LPS stimulation and membrane-anchored
      CD14 expression on the cell surface. Our data suggest that down-regulation of GPI
      PLD could play an important role in the control of proinflammatory responses.

PMID- 11292744
TI  - C-terminal invariable domain of VlsE is immunodominant but its antigenicity is
      scarcely conserved among strains of Lyme disease spirochetes.
AB  - VlsE, the variable surface antigen of Borrelia burgdorferi, contains two
      invariable domains located at the amino and carboxyl terminal ends, respectively,
      and a central variable domain. In this study, both immunogenicity and antigenic
      conservation of the C-terminal invariable domain were assessed. Mouse antiserum
      to a 51-mer synthetic peptide (Ct) which reproduced the entire sequence of the C
      terminal invariable domain of VlsE from B. burgdorferi strain B31 was reacted on
      immunoblots with whole-cell lysates extracted from spirochetes of 12 strains from
      the B. burgdorferi sensu lato species complex. The antiserum recognized only VlsE
      from strain B31, indicating that epitopes of this domain differed among these
      strains. When Ct was used as enzyme-linked immunosorbent assay (ELISA) antigen,
      all of the seven monkeys and six mice that were infected with B31 spirochetes
      produced a strong antibody response to this peptide, indicating that the C
      terminal invariable domain is immunodominant. None of 12 monkeys and only 11 of
      26 mice that were infected with strains other than B31 produced a detectable anti
      Ct response, indicating a limited antigenic conservation of this domain among
      these strains. Twenty-six of 33 dogs that were experimentally infected by tick
      inoculation were positive by the Ct ELISA, while only 5 of 18 serum samples from
      dogs clinically diagnosed with Lyme disease contained detectable anti-Ct
      antibody. Fifty-seven of 64 serum specimens that were collected from American
      patients with Lyme disease were positive by the Ct ELISA, while only 12 of 21
      European samples contained detectable anti-Ct antibody. In contrast, antibody to
      the more conserved invariable region IR(6) of VlsE was present in all of these
      dog and human serum samples.

PMID- 11292745
TI  - Flow cytometric determination of cellular sources and frequencies of key cytokine
      producing lymphocytes directed against recombinant LACK and soluble Leishmania
      antigen in human cutaneous leishmaniasis.
AB  - Leishmaniasis, caused by infection with the protozoan parasite Leishmania,
      affects millions of individuals worldwide, causing serious morbidity and
      mortality. This study directly determined the frequency of cells producing key
      immunoregulatory cytokines in response to the recombinant antigen Leishmania
      homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen
      (SLA), and it determined relative contributions of these antigens to the overall
      cytokine profile in individuals infected for the first time with Leishmania
      braziliensis. All individuals presented with the cutaneous clinical form of
      leishmaniasis and were analyzed for proliferative responses to LACK antigen and
      SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen
      induced (LACK and SLA) cytokine production at the single-cell level (determined
      by flow cytometry). The following were determined. (i) The Th1-type response
      previously seen in patients with cutaneous leishmaniasis is due to gamma
      interferon (IFN-gamma) production by several different sources, listed in order
      of contribution: CD4(+) T lymphocytes, CD4(-), CD8(-) lymphocytes, and CD8(+) T
      lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN
      gamma and tumor necrosis factor alpha (TNF-alpha) than did LACK. (iii) LACK
      induced an activation of monocyte populations as reflected by an increased
      percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable
      frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data
      demonstrated a multifaceted immune response to SLA in human leishmaniasis
      involving Th1 CD4(+) T lymphocytes (IFN-gamma(+) and IL-10(-)/IL-4(-)), Tc1
      CD8(+) T cells (IFN-gamma(+), and IL-10(-)/IL-4(-)), and a high frequency of TNF
      alpha-producing lymphocytes. Moreover, it was determined that the recombinant
      antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to
      SLA.

PMID- 11292746
TI  - Shigella infection in a SCID mouse-human intestinal xenograft model: role for
      neutrophils in containing bacterial dissemination in human intestine.
AB  - Shigellae infect human intestine and cause intense inflammation and destruction
      of colonic and rectal mucosa. To model the interactions of shigella with human
      intestine in vivo, we have studied shigella infection in human intestinal
      xenografts in severe combined immunodeficient mice (SCID-HU-INT mice).
      Inoculation of shigella into human intestinal xenografts caused severe
      inflammation and mucosal damage, which was apparent as soon as 4 h following
      infection. Shigella infection was associated with human intestinal production of
      interleukin-1B (IL-1B) and IL-8 and a marked neutrophil influx into the graft.
      Depletion of neutrophils from SCID-HU-INT mice reduced inflammation in the human
      intestinal xenograft in response to shigella infection but failed to
      significantly alter tissue damage. However, the number of intracellular bacteria
      was more than 20-fold higher in the human intestinal xenografts from neutrophil
      depleted SCID-HU-INT mice. Infection of human intestinal xenografts with an
      attenuated vaccine strain of shigella (CVD1203) induced lower levels of IL-1B and
      IL-8 than wild-type shigella and caused only moderate damage to the intestinal
      permeability barrier. Our studies establish the SCID-HU-INT mouse as a viable
      model for studying the interactions between shigella and human intestine and
      indicate that neutrophils are important for controlling the invasion of human
      intestine by shigella.

PMID- 11292747
TI  - Calprotectin expression by gingival epithelial cells.
AB  - Calprotectin, a heterodimer of MRP8 and MRP14 with antimicrobial properties, is
      found in the cytosol of neutrophils, monocytes, and human gingival keratinocytes.
      During inflammation of the oral mucosa, the expression of immunoreactive
      calprotectin appears upregulated. Given the possible cell sources, we sought to
      learn if epithelial cells upregulate calprotectin in response to proinflammmatory
      agents. First, human gingival keratinocytes were maintained in primary culture
      until senescence. At each passage, cells were harvested and analyzed for
      quantitative expression of MRP8 and MRP14 subunit mRNA by RNase protection assays
      and calprotectin complex by enzyme-linked immunosorbent assay. Calprotectin
      expression was constitutive in the primary gingival keratinocytes, but
      calprotectin-specific mRNA and protein tended to increase as the cells neared
      senescence. To test whether calprotectin expression was inducible, immortalized
      gingival keratinocyte cultures were treated for 2 to 4 h with lipopolysaccharide
      (LPS) or interleukin-1 beta (IL-1 beta). As a positive control for inducible
      expression, immortalized keratinocytes were incubated with phorbol myristate
      acetate (PMA) (50 ng/ml) for 24 h. Incubation with PMA stimulated increased
      expression of MRP8 and MRP14 mRNA within 2 h, peaking within 5 h. MRP8- and MRP14
      specific mRNA expression by immortalized keratinocytes appeared to be unaffected
      by LPS or IL-1 beta. In contrast, LPS, IL-1 beta, and PMA each upregulated IL-8.
      These data show that calprotectin mRNA is expressed constitutively in cultured
      keratinocytes, while expression by immortalized cells appears to be independent
      of the exogenous proinflammatory agents LPS and IL-1 beta.

PMID- 11292748
TI  - Vaccination against the intracellular pathogens Leishmania major and L.
      amazonensis by directing CD40 ligand to macrophages.
AB  - CD40 ligand (CD40L) is a potent inducer of interleukin-12 (IL-12) production from
      macrophages and dendritic cells. We show that combining CD40L with antigen
      derived from Leishmania is an effective way to preferentially induce type 1
      immune responses to the antigen and to vaccinate mice against subsequent
      challenge with virulent organisms. Mice vaccinated in this way had smaller
      lesions, with more than 1,000-fold fewer parasites within them. To improve the
      efficiency of CD40L-induced immunopotentiation, we attempted to specifically
      direct CD40L to macrophages. We developed transfected cells expressing CD40L and
      a single Leishmania antigen, gp63. These cells bound efficiently to macrophages
      and induced robust IL-12 production. Vaccination with these cotransfected cells
      provided a significant degree of protection against challenge with virulent
      organisms. CD40L was also adsorbed to the surface of virulent Leishmania. These
      organisms induced only modest lesions in genetically susceptible mice, and the
      lesions had an average of 10(5)-fold fewer organisms within them relative to
      control mice. These studies suggest that CD40L could be exploited to improve
      vaccines against intracellular pathogens, especially those organisms that reside
      within cells expressing CD40 on their surface.

PMID- 11292749
TI  - Immunological basis for reactivation of tuberculosis in mice.
AB  - In this study different inbred strains of mice appeared to control and contain a
      low dose aerosol infection with Mycobacterium tuberculosis in a similar manner,
      giving rise to a chronic state of disease. Thereafter, however, certain strains
      gradually began to show evidence of regrowth of the infection, whereas others
      consistently did not. Using C57BL/6 mice as an example of a resistant strain and
      CBA/J mice as an example of a strain susceptible to bacterial growth, we found
      that these animals revealed distinct differences in the cellular makeup of lung
      granulomas. The CBA/J mice exhibited a generally poor lymphocyte response within
      the lungs and vastly increased degenerative pathology at a time associated with
      regrowth of the infection. As a possible explanation for these events, it was
      then observed that the CBA/J mouse strain was also less able to upregulate
      adhesion molecules, including CD11a and CD54, on circulating lymphocytes. These
      results therefore suggest that a failure to control a chronic infection with M.
      tuberculosis may reflect an inability to localize antigen-specific lymphocytes
      within the lung.

PMID- 11292750
TI  - Complete DNA sequence and analysis of the large virulence plasmid of Shigella
      flexneri.
AB  - The complete sequence analysis of the 210-kb Shigella flexneri 5a virulence
      plasmid was determined. Shigella spp. cause dysentery and diarrhea by invasion
      and spread through the colonic mucosa. Most of the known Shigella virulence
      determinants are encoded on a large plasmid that is unique to virulent strains of
      Shigella and enteroinvasive Escherichia coli; these known genes account for
      approximately 30 to 35% of the virulence plasmid. In the complete sequence of the
      virulence plasmid, 286 open reading frames (ORFs) were identified. An astonishing
      153 (53%) of these were related to known and putative insertion sequence (IS)
      elements; no known bacterial plasmid has previously been described with such a
      high proportion of IS elements. Four new IS elements were identified. Fifty
      putative proteins show no significant homology to proteins of known function; of
      these, 18 have a G+C content of less than 40%, typical of known virulence genes
      on the plasmid. These 18 constitute potentially unknown virulence genes. Two
      alleles of shet2 and five alleles of ipaH were also identified on the plasmid.
      Thus, the plasmid sequence suggests a remarkable history of IS-mediated
      acquisition of DNA across bacterial species. The complete sequence will permit
      targeted characterization of potential new Shigella virulence determinants.

PMID- 11292751
TI  - Specificity of the protective antibody response to apical membrane antigen 1.
AB  - Apical membrane antigen 1 (AMA1) is considered one of the leading candidates for
      inclusion in a vaccine against blood stages of Plasmodium falciparum. Although
      the ama1 gene is relatively conserved compared to those for some other potential
      vaccine components, numerous point mutations have resulted in amino acid
      substitutions at many sites in the polypeptide. The polymorphisms in AMA1 have
      been attributed to the diversifying selection pressure of the protective immune
      responses. It was therefore of interest to investigate the impact of sequence
      diversity in P. falciparum AMA1 on the ability of anti-AMA1 antibodies to inhibit
      the invasion of erythrocytes in vitro by P. falciparum merozoites. For these
      studies, we used antibodies to recombinant P. falciparum 3D7 AMA1 ectodomain,
      which was prepared for testing in early clinical trials. Antibodies were raised
      in rabbits to the antigen formulated in Montanide ISA720, and human antibodies to
      AMA1 were isolated by affinity purification from the plasma of adults living in
      regions of Papua New Guinea where malaria is endemic. Both rabbit and human anti
      AMA1 antibodies were found to be strongly inhibitory to the invasion of
      erythrocytes by merozoites from both the homologous and two heterologous lines of
      P. falciparum. The inhibitory antibodies targeted both conserved and strain
      specific epitopes within the ectodomain of AMA1; however, it appears that the
      majority of these antibodies reacted with strain-specific epitopes in domain I,
      the N-terminal disulfide-bonded domain, which is the most polymorphic region of
      AMA1.

PMID- 11292752
TI  - Effector mechanisms of protection against Pseudomonas aeruginosa keratitis in
      immunized rats.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen which causes sight
      threatening corneal infections in humans. The purpose of this study was to
      evaluate various immunization routes that may provide protection against
      Pseudomonas keratitis and to define the molecular mechanisms involved in the
      protection. Sprague-Dawley rats (10 to 12 weeks old) were immunized using
      paraformaldehyde-killed P. aeruginosa (strain 6206) via oral, nasal, and intra
      Peyer's patch (IPP) routes followed by an ocular topical booster dose. Scratched
      corneas were challenged with an infective dose of P. aeruginosa. Following
      clinical examination, eyes were enucleated for histology, polymorphonuclear
      leukocyte (PMN) quantitation, bacterial count, enzyme-linked immunosorbent assay,
      and RNase protection assay. PMN infiltration was higher early (4 h) during the
      infection in immunized rats than in nonimmunized rats. Later during the
      infection, the number of PMNs diminished in immunized rats while in nonimmunized
      animals the number of PMNs continued to increase. Bacteria were cleared much
      faster from immunized groups than from the nonimmunized group, and the nasally
      immunized group had the most efficacious response among the immunized groups.
      Nasal and IPP immunization groups had increased cytokine expression of
      interleukin-2 (IL-2) and IL-5 and differed from each other for IL-6. All three
      immunized groups had significantly reduced IL-1 beta levels when compared with
      the nonimmunized rats and a significantly altered profile for CINC-1 expression.
      This study has shown that the route of immunization modulates the inflammatory
      response to ocular P. aeruginosa infection, thus affecting the severity of
      keratitis and adverse pathology, with nasal immunization being the most
      effective.

PMID- 11292754
TI  - Recruitment of cytoskeletal and signaling proteins to enteropathogenic and
      enterohemorrhagic Escherichia coli pedestals.
AB  - Enteropathogenic Escherichia coli (EPEC) is a human pathogen that attaches to
      intestinal epithelial cells and causes chronic watery diarrhea. A close relative,
      enterohemorrhagic E. coli (EHEC), causes severe bloody diarrhea and hemolytic
      uremic syndrome. Both pathogens insert a protein, Tir, into the host cell plasma
      membrane where it binds intimin, the outer membrane ligand of EPEC and EHEC. This
      interaction triggers a cascade of signaling events within the host cell and
      ultimately leads to the formation of an actin-rich pedestal upon which the
      pathogen resides. Pedestal formation is critical in mediating EPEC- and EHEC
      induced diarrhea, yet very little is known about its composition and
      organization. In EPEC, pedestal formation requires Tir tyrosine 474
      phosphorylation. In EHEC Tir is not tyrosine phosphorylated, yet the pedestals
      appear similar. The composition of the EPEC and EHEC pedestals was analyzed by
      examining numerous cytoskeletal, signaling, and adapter proteins. Of the 25
      proteins examined, only two, calpactin and CD44, were recruited to the site of
      bacterial attachment independently of Tir. Several others, including ezrin,
      talin, gelsolin, and tropomyosin, were recruited to the site of EPEC attachment
      independently of Tir tyrosine 474 phosphorylation but required Tir in the host
      membrane. The remaining proteins were recruited to the pedestal in a manner
      dependent on Tir tyrosine phosphorylation or were not recruited at all.
      Differences were also found between the EPEC and EHEC pedestals: the adapter
      proteins Grb2 and CrkII were recruited to the EPEC pedestal but were absent in
      the EHEC pedestal. These results demonstrate that although EPEC and EHEC recruit
      similar cytoskeletal proteins, there are also significant differences in pedestal
      composition.

PMID- 11292753
TI  - Antibodies to a surface-exposed, N-terminal domain of aggregation substance are
      not protective in the rabbit model of Enterococcus faecalis infective
      endocarditis.
AB  - The aggregation substance (AS) surface protein from Enterococcus faecalis has
      been implicated as an important virulence factor for the development of infective
      endocarditis. To evaluate the role of antibodies specific for Asc10 (the AS
      protein from the conjugative plasmid pCF10) in protective immunity to infective
      endocarditis, an N-terminal region of Asc10 lacking the signal peptide and
      predicted to be surface exposed (amino acids 44 to 331; AS(44-331)) was cloned
      with a C-terminal histidine tag translational fusion and expressed from
      Escherichia coli. N-terminal amino acid sequencing of the purified protein
      revealed the correct sequence, and rabbit polyclonal antisera raised against
      AS(44-331) reacted specifically to Asc10 expressed from E. faecalis OG1SSp, but
      not to other proteins as judged by Western blot analysis. Using these antisera,
      flow cytometry analysis demonstrated that antibodies to AS(44-331) bound to a
      surface-exposed region of Asc10. Furthermore, antibodies specific for AS(44-331)
      were opsonic for E. faecalis expressing Asc10 in vitro but not for cells that did
      not express Asc10. New Zealand White rabbits immunized with AS(44-331) were
      challenged intravenously with E. faecalis cells constitutively expressing Asc10
      in the rabbit model of experimental endocarditis. Highly immune animals did not
      show significant differences in clearance of organisms from the blood or spleen
      or in formation of vegetations on the aortic valve, in comparison with nonimmune
      animals. Although in vivo expression of Asc10 was demonstrated by
      immunohistochemistry, these experiments provide evidence that immunity to Asc10
      does not play a role in protection from experimental infective endocarditis due
      to E. faecalis and may have important implications for the development of
      immunological approaches to combat enterococcal endocarditis.

PMID- 11292755
TI  - P13, an integral membrane protein of Borrelia burgdorferi, is C-terminally
      processed and contains surface-exposed domains.
AB  - To elucidate antigens present on the bacterial surface of Borrelia burgdorferi
      sensu lato that may be involved in pathogenesis, we characterized a protein, P13,
      with an apparent molecular mass of 13 kDa. The protein was immunogenic and was
      expressed in large amounts during in vitro cultivation compared to other known
      antigens. An immunofluorescence assay, immunoelectron microscopy, and protease
      sensitivity assays indicated that P13 is surface exposed. The deduced sequence of
      the P13 peptide revealed a possible signal peptidase type I cleavage site, and
      computer analysis predicted that P13 is an integral membrane protein with three
      transmembrane-spanning domains. Mass spectrometry, in vitro translation, and N-
      and C-terminal amino acid sequencing analyses indicated that P13 was
      posttranslationally processed at both ends and modified by an unknown mechanism.
      Furthermore, p13 belongs to a gene family with five additional members in B.
      burgdorferi sensu stricto. The p13 gene is located on the linear chromosome of
      the bacterium, in contrast to five paralogous genes, which are located on
      extrachromosomal plasmids. The size of the p13 transcript was consistent with a
      monocistronic transcript. This new gene family may be involved in functions that
      are specific for this spirochete and its pathogenesis.

PMID- 11292756
TI  - Monoclonal antibodies specific for Neisseria meningitidis group B polysaccharide
      and their peptide mimotopes.
AB  - From five mice immunized with Escherichia coli K1 bacteria, we produced 12
      immunoglobulin M hybridomas secreting monoclonal antibodies (MAbs) that bind to
      Neisseria meningitidis group B (NMGB). The 12 MAbs also bound the capsular
      polysaccharide (PS) of E. coli K1 [which, like NMGB, is alpha(2-8)-linked
      polysialic acid (PSA)] and bound to EV36, a nonpathogenic E. coli K-12 strain
      producing alpha(2-8) PSA. Except for HmenB5, which cross-reacted with N.
      meningitidis group C, none of the MAbs bound to N. meningitidis groups A, C, and
      Y. Of the 12 MAbs, 6 were autoantibodies as defined by binding to CHP-134, a
      neuroblastoma cell line expressing short-chain alpha(2-8) PSA; five of these MAbs
      killed NMGB in the presence of rabbit complement, and two also killed NMGB with
      human complement. The other six MAbs, however, were nonautoreactive; all killed
      NMGB with rabbit complement, and five killed NMGB with human complement. To
      obtain peptide mimotopes of NMGB PS, four of the nonautoreactive MAbs (HmenB2,
      HmenB3, HmenB13, and HmenB14) were used to screen two types of phage libraries,
      one with a linear peptide of 7 amino acids and the other with a circular peptide
      of 7 amino acids inserted between two linked cysteines. We obtained 86 phage
      clones that bound to the screening MAb in the absence but not in the presence of
      E. coli K1 PSA in solution. The clones contained 31 linear and 4 circular
      mimotopes expressing unique sequences. These mimotopes nonrandomly expressed
      amino acids and were different from previously described mimotopes for NMGB PS.
      The new mimotopes may be useful in producing a vaccine(s) capable of eliciting
      anti-NMGB antibodies not reactive with neuronal tissue.

PMID- 11292757
TI  - Fas-mediated apoptosis of neutrophils in sera of patients with infection.
AB  - In the presence of infection, neutropenia is considered to be a marker of poor
      prognosis; conversely, neutrophilia may not be a determinant of a better
      prognosis. Since apoptotic neutrophils are compromised functionally, we evaluated
      the effect of infection on neutrophil apoptosis. The rate of apoptosis was
      greater for neutrophils isolated from patients with infection than for healthy
      controls. Escherichia coli did not directly modulate the rate of neutrophil
      apoptosis. However, sera from infected patients promoted (P < 0.001) neutrophil
      apoptosis. Interestingly, the sera of patients with different types of infection
      (gram negative, gram positive, or culture negative) exerted a more or less
      identical response on neutrophil apoptosis. Sera of infected patients showed a
      fivefold greater content of FasL compared to controls. Moreover, anti-FasL
      antibody partly attenuated the infected-serum-induced neutrophil apoptosis. In in
      vitro studies, E. coli enhanced monocyte FasL expression. Moreover, conditioned
      media prepared from activated macrophages from control mice showed enhanced
      apoptosis of human as well as mouse neutrophils. On the contrary, conditioned
      media prepared from activated macrophages isolated from FasL-deficient mice
      induced only a mild degree of neutrophil apoptosis. These results suggest that
      neutrophils in patients with infection undergo apoptosis at an accelerated rate.
      Infection not only promoted monocyte expression of FasL but also increased FasL
      content of the serum. Because the functional status of apoptotic cells is
      compromised, a significant number of neutrophils may not be participating in the
      body's defense. Since neutrophils play the most important role in innate
      immunity, their compromised status in the presence of infection may transfer the
      host defense burden from an innate response to acquired immunity. The present
      study provides some insight into the lack of correlation between neutrophilia and
      the outcome of infection.

PMID- 11292758
TI  - Visualizing pneumococcal infections in the lungs of live mice using
      bioluminescent Streptococcus pneumoniae transformed with a novel gram-positive
      lux transposon.
AB  - Animal studies with Streptococcus pneumoniae have provided valuable models for
      drug development. In order to monitor long-term pneumococcal infections
      noninvasively in living mice, a novel gram-positive lux transposon cassette,
      Tn4001 luxABCDE Km(r), that allows random integration of lux genes onto the
      bacterial chromosome was constructed. The cassette was designed so that the
      luxABCDE and kanamycin resistance genes were linked to form a single promoterless
      operon. Bioluminescence and kanamycin resistance only occur in a bacterial cell
      if this operon has transposed downstream of a promoter on the bacterium's
      chromosome. S. pneumoniae D39 was transformed with plasmid pAUL-A Tn4001 luxABCDE
      Km(r), and a number of highly bioluminescent colonies were recovered. Genomic DNA
      from the brightest D39 strain was used to transform a number of clinical S.
      pneumoniae isolates, and several of these strains were tested in animal models,
      including a pneumococcal lung infection model. Strong bioluminescent signals were
      seen in the lungs of the animals containing these pneumococci, allowing the
      course and antibiotic treatment of the infections to be readily monitored in real
      time in the living animals. Recovery of the bacteria from the animals showed that
      the bioluminescent signal corresponded to the number of CFU and that the lux
      construct was highly stable even after several days in vivo. We believe that this
      lux transposon will greatly expand the ability to evaluate drug efficacy against
      gram-positive bacteria in living animals using bioluminescence.

PMID- 11292759
TI  - Coinfection with Borrelia burgdorferi and the agent of human granulocytic
      ehrlichiosis alters murine immune responses, pathogen burden, and severity of
      Lyme arthritis.
AB  - Lyme disease and human granulocytic ehrlichiosis (HGE) are tick-borne illnesses
      caused by Borrelia burgdorferi and the agent of HGE, respectively. We
      investigated the influence of dual infection with B. burgdorferi and the HGE
      agent on the course of murine Lyme arthritis and granulocytic ehrlichiosis.
      Coinfection resulted in increased levels of both pathogens and more severe Lyme
      arthritis compared with those in mice infected with B. burgdorferi alone. The
      increase in bacterial burden during dual infection was associated with enhanced
      acquisition of both organisms by larval ticks that were allowed to engorge upon
      infected mice. Coinfection also resulted in diminished interleukin-12 (IL-12),
      gamma interferon (IFN-gamma), and tumor necrosis factor alpha levels and elevated
      IL-6 levels in murine sera. During dual infection, IFN-gamma receptor expression
      on macrophages was also reduced, implying a decrease in phagocyte activation.
      These results suggest that coinfection of mice with B. burgdorferi and the HGE
      agent modulates host immune responses, resulting in increased bacterial burden,
      Lyme arthritis, and pathogen transmission to the vector.

PMID- 11292760
TI  - Characterization of binding of human lactoferrin to pneumococcal surface protein
      A.
AB  - Human lactoferrin is an iron-binding glycoprotein that is particularly prominent
      in exocrine secretions and leukocytes and is also found in serum, especially
      during inflammation. It is able to sequester iron from microbes and has
      immunomodulatory functions, including inhibition of both complement activation
      and cytokine production. This study used mutants lacking pneumococcal surface
      protein A (PspA) and PspC to demonstrate that the binding of human lactoferrin to
      the surface of Streptococcus pneumoniae was entirely dependent on PspA.
      Lactoferrin bound both family 1 and family 2 PspAs. Binding of lactoferrin to
      PspA was shown by surface colocalization with PspA and was verified by the lack
      of binding to PspA-negative mutants. Lactoferrin was expressed on the body of the
      cells but was largely absent from the poles. PspC showed exactly the same
      distribution on the pneumococcal surface as PspA but did not bind lactoferrin.
      PspA's binding site for lactoferrin was mapped using recombinant fragments of
      PspA of families 1 and 2. Binding of human lactoferrin was detected primarily in
      the C-terminal half of the alpha-helical domain of PspA (amino acids 167 to 288
      of PspA/Rx1), with no binding to the N-terminal 115 amino acids in either strain.
      The interaction was highly specific. As observed previously, bovine lactoferrin
      bound poorly to PspA. Human transferrin did not bind PspA at all. The binding of
      lactoferrin to S. pneumoniae might provide a way for the bacteria to interfere
      with host immune functions or to aid in the acquisition of iron at the site of
      infection.

PMID- 11292761
TI  - Amebic infection in the human colon induces cyclooxygenase-2.
AB  - We sought to determine if infection of the colon with Entamoeba histolytica
      induces the expression of cyclooxygenase-2 and, if it does, to determine the
      contribution of prostaglandins produced through cyclooxygenase-2 to the host
      response to amebic infection. Human fetal intestinal xenografts were implanted
      subcutaneously in mice with severe combined immunodeficiency and allowed to grow;
      the xenografts were then infected with E. histolytica trophozoites. Infection
      with E. histolytica resulted in the expression of cyclooxygenase-2 in epithelial
      cells and lamina propria macrophages. Infection with E. histolytica increased
      prostaglandin E(2) (PGE2) levels 10-fold in the xenografts and resulted in
      neutrophil infiltration, as manifested by an 18-fold increase in myeloperoxidase
      activity. Amebic infection also induced an 18-fold increase in interleukin 8 (IL
      8) production and a >100-fold increase in epithelial permeability. Treatment of
      the host mouse with indomethacin, an inhibitor of cyclooxygenase-1 and
      cyclooxygenase-2, or with NS-398, a selective inhibitor of cyclooxygenase-2,
      resulted in (i) decreased PGE(2) levels, (ii) a decrease in neutrophil
      infiltration, (iii) a decrease in IL-8 production, and (iv) a decrease in the
      enhanced epithelial permeability seen with amebic infection. These results
      indicate that amebic infection in the colon induces the expression of
      cyclooxygenase-2 in epithelial cells and macrophages. Moreover, prostaglandins
      produced through cyclooxygenase-2 participate in the mediation of the neutrophil
      response to infection and enhance epithelial permeability.

PMID- 11292762
TI  - Isogenic serotypes of Borrelia turicatae show different localization in the brain
      and skin of mice.
AB  - Mice with severe combined immunodeficiency (scid mice) and infected with the
      relapsing fever agent Borrelia turicatae develop manifestations that resemble
      those of disseminated Lyme disease. We have characterized two isogenic serotypes,
      A and B, which differ in their variable small proteins (Vsps) and disease
      manifestations. Serotype A but not serotype B was cultured from the brain during
      early infection, and serotype B caused more severe arthritis, myocarditis, and
      vestibular dysfunction than serotype A. Here we compared the localization and
      number of spirochetes and the severity of inflammation in scid mice, using
      immunostained and hematoxylin-and-eosin-stained coronal sections of decalcified
      heads. Spirochetes in the brain localized predominantly to the leptomeninges, and
      those in peripheral tissues localized mainly to the extracellular matrix. There
      were significantly more serotype A than B spirochetes in the leptomeninges and
      more serotype B than A spirochetes in the skin. The first tissue where
      spirochetes were observed outside the vasculature was the dura mater.
      Inflammation was more severe in the skin than in the brain. VspA, VspB, and the
      periplasmic flagellin protein were expressed in all tissues examined. These
      findings indicate that isogenic but antigenically distinct Borrelia serotypes can
      have marked differences in their localization in tissues.

PMID- 11292764
TI  - Passive immunization with melanin-binding monoclonal antibodies prolongs survival
      of mice with lethal Cryptococcus neoformans infection.
AB  - Passive immunization with monoclonal antibodies (MAbs) to melanin prolonged the
      survival of and reduced the fungal burden in Cryptococcus neoformans-infected
      mice in comparison to controls. MAbs to melanin reduced the growth rate of in
      vitro-melanized C. neoformans cells, suggesting a new mechanism of antibody
      mediated protection.

PMID- 11292763
TI  - Molecular basis for immunoglobulin M specificity to epitopes in Cryptococcus
      neoformans polysaccharide that elicit protective and nonprotective antibodies.
AB  - The protective efficacy of antibodies (Abs) to Cryptococcus neoformans
      glucuronoxylomannan (GXM) is dependent on Ab fine specificity. Two clonally
      related immunoglobulin M monoclonal Abs (MAbs) (12A1 and 13F1) differ in fine
      specificity and protective efficacy, presumably due to variable (V)-region
      sequence differences resulting from somatic mutations. MAb 12A1 is protective and
      produces annular immunofluorescence (IF) on serotype D C. neoformans, while MAb
      13F1 is not protective and produces punctate IF. To determine the Ab molecular
      determinants responsible for the IF pattern, site-directed mutagenesis of the MAb
      12A1 heavy-chain V region (V(H)) was followed by serological and functional
      studies of the various mutants. Changing two selected amino acids in the 12A1
      V(H) binding cavity to the corresponding residues in the 13F1 V(H) altered the IF
      pattern from annular to punctate, reduced opsonic efficacy, and abolished
      recognition by an anti-idiotypic Ab. Analysis of the binding of the various
      mutants to peptide mimetics revealed that different amino acids were responsible
      for GXM binding and peptide specificity. The results suggest that V-region motifs
      associated with annular binding and opsonic activity may be predictive of Ab
      efficacy against C. neoformans. This has important implications for immunotherapy
      and vaccine design that are reinforced by the finding that GXM and peptide
      reactivities are determined by different amino acid residues.

PMID- 11292765
TI  - Immunohistochemical analysis of cellular infiltrate and gamma interferon,
      interleukin-12, and inducible nitric oxide synthase expression in leprosy type 1
      (reversal) reactions before and during prednisolone treatment.
AB  - The effects of prednisolone treatment on the cellularity and cytokine (gamma
      interferon, interleukin-12, and inducible nitric oxide synthase) profiles of
      leprosy skin type 1 (reversal) reactions were studied using immunohistochemistry.
      Skin biopsies were taken from 15 patients with leprosy type 1 (reversal)
      reactions at days 0, 7, 28, and 180 after the start of steroid treatment.
      Prednisolone treatment had little effect at day 7, but by day 28 significant
      decreases were found in cytokine levels. Some patients maintained cytokine
      production at days 28 and 180. These results illustrate the strong Th1 profile of
      type 1 reactional lesions, the slow response to steroid therapy, and continuing
      activity at 180 days.

PMID- 11292766
TI  - Escherichia coli CdtB mediates cytolethal distending toxin cell cycle arrest.
AB  - We previously reported that the CdtB polypeptide of Escherichia coli cytolethal
      distending toxin (CDT) shares significant pattern-specific homology with
      mammalian type I DNases. In addition, the DNase-related residues of CdtB are
      required for cellular toxicity. Here we demonstrate that purified CdtB converts
      supercoiled plasmid DNA to relaxed and linear forms and promotes cell cycle
      arrest when combined with an E. coli extract containing CdtA and CdtC. CdtB alone
      had no effect on HeLa cells, however; introduction of the polypeptide into HeLa
      cells by electroporation resulted in cellular distension, chromatin
      fragmentation, and cell cycle arrest, all of which are consequences of CDT
      action. In contrast to these findings, purified CdtB(H154A) lacked both DNA
      nicking and cell cycle arrest activities. These results suggest a functional
      relationship between DNase-related residues in CdtB and CDT biological activity.

PMID- 11292767
TI  - Key role of teichoic acid net charge in Staphylococcus aureus colonization of
      artificial surfaces.
AB  - Staphylococcus aureus is responsible for a large percentage of infections
      associated with implanted biomedical devices. The molecular basis of primary
      adhesion to artificial surfaces is not yet understood. Here, we demonstrate that
      teichoic acids, highly charged cell wall polymers, play a key role in the first
      step of biofilm formation. An S. aureus mutant bearing a stronger negative
      surface charge due to the lack of D-alanine esters in its teichoic acids can no
      longer colonize polystyrene or glass. The mutation abrogates primary adhesion to
      plastic while production of the glucosamine-based polymer involved in later steps
      of biofilm formation is not affected. Our data suggest that repulsive
      electrostatic forces can lead to reduced staphylococcal biofilm formation, which
      could have considerable impact on the design of novel implanted materials.

PMID- 11292768
TI  - Protective cytotoxic T lymphocyte responses induced by DNA immunization against
      immunodominant and subdominant epitopes of Listeria monocytogenes are
      noncompetitive.
AB  - Taking advantage of the fact that plasmid DNA encoding a single cytotoxic T
      lymphocyte (CTL) epitope can induce CTLs, we examined the influence of T-cell
      responses to dominant epitopes on those to a subdominant epitope derived from
      Listeria monocytogenes. Our data suggest that interaction between T cells against
      dominant and subdominant epitopes does not operate in the generation of the
      hierarchy. Furthermore, we found that a single dominant epitope is sufficient for
      the induction of protective immunity.

PMID- 11292769
TI  - Periodontal pathogens produce quorum sensing signal molecules.
AB  - Different species of bacteria important in the composition of dental plaque were
      tested for production of extracellular autoinducer-like activities that stimulate
      the expression of the luminescence genes in Vibrio harveyi. Several strains of
      Prevotella intermedia, Fusobacterium nucleatum, and Porphyromonas gingivalis were
      found to produce such activities. Interestingly, these bacteria belong to the
      same phylogenetic group, and they are periodontal pathogens important in the
      development of periodontal disease. They specifically produce extracellular
      signaling molecule related autoinducer-2 from V. haveyi. Nevertheless, they seem
      to be unable to produce homologues of acyl-homoserine lactones. Furthermore,
      Escherichia coli DH5alpha can be complemented by the introduction of a P.
      gingivalis gene with high homology to the luxS gene, which has been called
      luxS(P.g.).

PMID- 11292770
TI  - PspC, a pneumococcal surface protein, binds human factor H.
AB  - PspC was found to bind human complement factor H (FH) by Western blot analysis of
      D39 (pspC(+)) and an isogenic mutant TRE108 (pspC). We confirmed that PspA does
      not bind FH, while purified PspC binds FH very strongly. The binding of FH to
      exponentially growing pneumococci varied among different isolates when analyzed
      by fluorescence activated cell sorting analysis.

PMID- 11292771
TI  - Heat-inducible surface stress protein (Hsp70) mediates sulfatide recognition of
      the respiratory pathogen Haemophilus influenzae.
AB  - The in vitro glycolipid binding specificity of clinical strains of nontypeable
      Haemophilus influenzae is altered to include sulfated glycolipids following a
      brief heat shock. We have constructed, expressed, and purified a recombinant
      protein of H. influenzae Hsp70, which showed significant specific binding to
      sulfated galactolipids in vitro. Furthermore, indirect immunofluorescence
      demonstrates that Hsp70 proteins are surface exposed in H. influenzae only after
      heat shock and are contained in the outer membrane protein fractions.

PMID- 11292772
TI  - Molecular and genomic analysis of genes encoding surface-anchored proteins from
      Clostridium difficile.
AB  - The gene slpA, encoding the S-layer precursor protein in the virulent Clostridium
      difficile strains C253 and 79--685, was identified. The precursor protein carries
      a C-terminal highly conserved anchoring domain, similar to the one found in the
      Cwp66 adhesin (previously characterized in strain 79--685), an SLH domain, and a
      variable N-terminal domain mediating cell adherence. The genes encoding the S
      layer precursor proteins and the Cwp66 adhesin are present in a genetic locus
      carrying 17 open reading frames, 11 of which encode a similar two-domain
      architecture, likely to include surface-anchored proteins.

PMID- 11292773
TI  - Sequence and antigenic variability of the Helicobacter mustelae surface ring
      protein Hsr.
AB  - We have identified an array of more than 500 repetitive sequences flanking the
      hsr gene, which encodes the major surface protein of the ferret pathogen
      Helicobacter mustelae. The repeats show identity exclusively to the amino
      terminal half of Hsr. Analysis of Hsr from three strains indicated variability of
      exposed epitopes. Characterization of an hsr mutant showed that Hsr is not an
      adhesin.

PMID- 11292774
TI  - Chlamydia trachomatis infection does not enhance local cellular immunity against
      concurrent Candida vaginal infection.
AB  - Although Th1-type cell-mediated immunity (CMI) is the predominant host defense
      mechanism against mucosal Candida albicans infection, CMI against a vaginal C.
      albicans infection in mice is limited at the vaginal mucosa despite a strong
      Candida-specific Th1-type response in the draining lymph nodes. In contrast, Th1
      type CMI is highly effective against an experimental Chlamydia trachomatis
      genital tract infection. This study demonstrated through two independent designs
      that a concurrent Candida and Chlamydia infection could not accelerate or
      modulate the anti-Candida CMI response. Together, these results suggest that host
      responses to these genital tract infections are independent and not influenced by
      the presence of the other.

PMID- 11292775
TI  - Delineation of Borrelia burgdorferi p66 sequences required for integrin
      alpha(IIb)beta(3) recognition.
AB  - The outer membrane protein p66 of the Lyme disease agent, Borrelia burgdorferi,
      has been identified as a candidate ligand for beta(3)-chain integrins. To
      identify portions of p66 required for integrin recognition, fusions of maltose
      binding protein to fragments of p66 were tested for binding to integrin
      alpha(IIb)beta(3), and synthetic peptides derived from the p66 amino acid
      sequence were tested for the ability to inhibit B. burgdorferi attachment to the
      same integrin. The data identify two noncontiguous segments of p66 that are
      important for alpha(IIb)beta(3) recognition, suggesting that, as is true for
      other integrin ligands, the tertiary structure of p66 is important for receptor
      recognition.

PMID- 11292776
TI  - Assessing vascular permeability during experimental cerebral malaria by a
      radiolabeled monoclonal antibody technique.
AB  - Vascular endothelial integrity, assessed by Evans blue dye extrusion and
      radiolabeled monoclonal antibody leakage, was markedly compromised in the brain,
      lung, kidney, and heart during Plasmodium berghei infection, a well-recognized
      model for human cerebral malaria. The results for vascular permeability from both
      methods were significantly (P < 0.001) related.

PMID- 11292777
TI  - Induction and distribution of intestinal immune responses after administration of
      recombinant cholera toxin B subunit in the ileal pouches of colectomized
      patients.
AB  - The induction and dissemination of mucosal immune responses to recombinant
      cholera toxin B subunit (rCTB) administered into the ileal pouches of patients,
      who had been colectomized because of ulcerative colitis, was analyzed. Biopsies
      from the duodenum and ileal pouch were collected, along with peripheral blood and
      ileostomy fluids. Two immunizations induced strong CTB-specific immunoglobulin A
      (IgA) antibody-secreting cell (ASC) responses in the duodenum in five of five
      patients, whereas weaker and less-frequent ASC responses were noted in the ileal
      pouch. Intestine-derived CTB-specific IgA ASCs were found in peripheral blood in
      three of the five patients. The vaccination also induced significant IgA
      antitoxin titer rises in ileostomy fluid in all of the patients. Increased
      production of gamma interferon in cell cultures from the ileal pouch was found in
      four of five patients after the vaccination. These results clearly indicate that
      rCTB administered into the distal ileum is capable of inducing B-cell responses
      in the "entire" small intestine and that homing of immunocompetent cells occurs
      preferentially to the duodenum.

PMID- 11292778
TI  - Shear stress prevents fibronectin binding protein-mediated Staphylococcus aureus
      adhesion to resting endothelial cells.
AB  - Fibronectin binding proteins (FnBP) on the surface of Staphylococcus aureus have
      previously been shown to mediate adherence of the organism to resting endothelial
      cells in static adhesion assays. However, in this study using well-defined flow
      assays, we demonstrate that physiologic levels of shear stress prevent FnBP
      mediated adhesion of S. aureus 8325-4 to resting endothelial cells. This result
      suggests that mechanical forces present in vivo may influence the ability of
      staphylococci to bind endothelial cell surfaces.

PMID- 11292779
TI  - Escherichia coli heat-labile enterotoxin B subunit is a more potent mucosal
      adjuvant than its vlosely related homologue, the B subunit of cholera toxin.
AB  - Although cholera toxin (Ctx) and Escherichia coli heat-labile enterotoxin (Etx)
      are known to be potent mucosal adjuvants, it remains controversial whether the
      adjuvanticity of the holotoxins extends to their nontoxic, receptor-binding B
      subunits. Here, we have systematically evaluated the comparative adjuvant
      properties of highly purified recombinant EtxB and CtxB. EtxB was found to be a
      more potent adjuvant than CtxB, stimulating responses to hen egg lysozyme when
      the two were coadministered to mice intranasally, as assessed by enhanced serum
      and secretory antibody titers as well as by stimulation of lymphocyte
      proliferation in spleen and draining lymph nodes. These results indicate that,
      although structurally very similar, EtxB and CtxB have strikingly different
      immunostimulatory properties and should not be considered equivalent as
      prospective vaccine adjuvants.

PMID- 11292780
TI  - Enterotoxin plasmid from Clostridium perfringens is conjugative.
AB  - Clostridium perfringens enterotoxin is the major virulence factor involved in the
      pathogenesis of C. perfringens type A food poisoning and several non-food-borne
      human gastrointestinal illnesses. The enterotoxin gene, cpe, is located on the
      chromosome of food-poisoning isolates but is found on a large plasmid in non-food
      borne gastrointestinal disease isolates and in veterinary isolates. To evaluate
      whether the cpe plasmid encodes its own conjugative transfer, a C. perfringens
      strain carrying pMRS4969, a plasmid in which a 0.4-kb segment internal to the cpe
      gene had been replaced by the chloramphenicol resistance gene catP, was used as a
      donor in matings with several cpe-negative C. perfringens isolates.
      Chloramphenicol resistance was transferred at frequencies ranging from 2.0 x 10(
      2) to 4.6 x 10(-4) transconjugants per donor cell. The transconjugants were
      characterized by PCR, pulsed-field gel electrophoresis, and Southern
      hybridization analyses. The results demonstrated that the entire pMRS4969 plasmid
      had been transferred to the recipient strain. Plasmid transfer required cell-to
      cell contact and was DNase resistant, indicating that transfer occurred by a
      conjugation mechanism. In addition, several fragments of the prototype C.
      perfringens tetracycline resistance plasmid, pCW3, hybridized with pMRS4969,
      suggesting that pCW3 shares some similarity to pMRS4969. The clinical
      significance of these findings is that if conjugative transfer of the cpe plasmid
      occurred in vivo, it would have the potential to convert cpe-negative C.
      perfringens strains in normal intestinal flora into strains capable of causing
      gastrointestinal disease.

PMID- 11292781
TI  - Preparation, immunogenicity, and protective efficacy, in a murine model, of a
      conjugate vaccine composed of the polysaccharide moiety of the lipopolysaccharide
      of Vibrio cholerae O139 bound to tetanus toxoid.
AB  - The epidemic and pandemic potential of Vibrio cholerae O139 is such that a
      vaccine against this newly emerged serogroup of V. cholerae is required. A
      conjugate made of the polysaccharide moiety (O-specific polysaccharide plus core)
      of the lipopolysaccharide (LPS) of V. cholerae O139 (pmLPS) was prepared by
      derivatization of the pmLPS with adipic acid dihydrazide and coupling to tetanus
      toxoid (TT) by carbodiimide-mediated condensation. The immunologic properties of
      the conjugate were tested using BALB/c mice injected subcutaneously three times
      at 2 weeks interval and then a fourth time 4 weeks later. Mice were bled 7 days
      after each injection and then once each month for the following 6 months. LPS and
      TT antibody levels were determined by enzyme-linked immunosorbent assay using
      immunoplates coated with either O139 LPS or TT. Both pmLPS and pmLPS-TT conjugate
      elicited low levels of immunoglobulin M (IgM), peaking 5 weeks after the first
      immunization. The conjugate elicited high levels of IgG antibodies, peaking 3
      months after the first immunization and declining slowly during the following 5
      months. TT alone, or as a component of conjugate, induced mostly IgG antibodies.
      Antibodies elicited by the conjugate recognized both capsular polysaccharide and
      LPS from V. cholerae O139 and were vibriocidal. They were also protective in the
      neonatal mouse model of cholera infection. The conjugation of the O139 pmLPS,
      therefore, enhanced its immunogenicity and conferred T-dependent properties to
      this polysaccharide.

PMID- 11292782
TI  - Pneumolysin potentiates production of prostaglandin E(2) and leukotriene B(4) by
      human neutrophils.
AB  - Exposure to pneumolysin (8.37 and 41.75 ng/ml) caused a calcium-dependent
      increase in the generation of prostaglandin E(2) and leukotriene B(4) by both
      resting and chemoattractant-activated human neutrophils in vitro. These
      interactions of pneumolysin with neutrophils may result in dysregulation of
      inflammatory responses during pneumococcal infection.

PMID- 11292783
TI  - Contribution of CD8(+) T cells to gamma interferon production in human
      tuberculosis.
AB  - The proportions of peripheral blood mononuclear cells (PBMC), CD4(+) T cells, and
      CD8(+) T cells that produce gamma interferon (IFN-gamma) in response to
      Mycobacterium tuberculosis were markedly reduced in tuberculosis patients,
      particularly in those with severe disease. Depletion of CD4(+) but not CD8(+)
      cells prior to stimulation of PBMC with M. tuberculosis abolished IFN-gamma
      production. These results show that (i) IFN-gamma production by CD8(+) and CD4(+)
      cells correlates with the clinical manifestations of M. tuberculosis infection
      and (ii) IFN-gamma production by CD8(+) cells depends on CD4(+) cells.

PMID- 11292784
TI  - Characterization of proteins in the outer membrane preparation of a murine
      pathogen, Helicobacter bilis.
AB  - Helicobacter bilis is a bacterial pathogen associated with multifocal hepatitis
      and inflammatory bowel disease in certain strains of mice. This bacterium
      colonizes the liver, bile, and lower intestine in mice and has also been isolated
      from a wide spectrum of laboratory animals. In this study, proteins present in
      the outer membrane preparation (OMP) of four H. bilis strains isolated from a
      mouse, a dog, a rat, and a gerbil were characterized and compared with that of
      Helicobacter pylori, a human gastric pathogen. All four H. bilis strains had
      similar OMP protein profiles that were distinct from those of H. pylori.
      Immunoblotting demonstrated that OMP proteins from H. bilis and H. pylori have
      little cross-reactivity, except for their flagellins. Nine major immunogenic
      polypeptides were present in the H. bilis OMPs. By using two-dimensional sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, five heat-modifiable proteins
      with molecular masses of 82, 66, 52, 47 and 37 kDa were identified. The N
      terminal sequences of the 46- and 47-kDa OMP proteins had no homology with
      protein sequences available in public databases. These results indicate that H.
      bilis has a conserved, unique OMP protein profile that is distinct from those of
      H. pylori.

PMID- 11292785
TI  - Dissociation of infectivity and pathogenicity in Borrelia burgdorferi.
AB  - Clonal Borrelia burgdorferi N40 (cN40) passaged 75 times in vitro (N40-75)
      infects mice but does not cause disease. N40-75 passaged 45 times further in
      vitro (N40-120) was no longer infectious and lacked genes encoded on linear
      plasmids 38 and 28-1, among other differences. These data suggest that B.
      burgdorferi cN40, N40-75, and N40-120 have distinct phenotypes that can be used
      to dissect the genetic elements responsible for pathogenicity and infectivity.

PMID- 11292787
TI  - YopB of Yersinia enterocolitica is essential for YopE translocation.
AB  - A previous study has shown that YopB of Yersinia spp. is essential for
      translocation of Yop effectors across the eucaryotic plasma membrane (M.-P. Sory
      and G. R. Cornelis, Mol. Microbiol. 14:583--594, 1994). However, this role was
      recently challenged (V. T. Lee and O. Schneewind, Mol. Microbiol. 31:1619--1629,
      1999). Using protease protection and digitonin extraction, we reconfirm that YopB
      of Yersinia enterocolitica is essential for the translocation of YopE into HeLa
      cell monolayers.

PMID- 11292786
TI  - Protection against Pseudomonas aeruginosa chronic lung infection in mice by
      genetic immunization against outer membrane protein F (OprF) of P. aeruginosa.
AB  - The Pseudomonas aeruginosa major constitutive outer membrane porin protein OprF,
      which has previously been shown to be a protective antigen, was targeted as a DNA
      vaccine candidate. The oprF gene was cloned into plasmid vector pVR1020, and the
      plasmid vaccines were delivered to mice by biolistic (gene gun) intradermal
      inoculation. Antibody titers in antisera from immunized mice were determined by
      enzyme-linked immunosorbent assay, and the elicited antibodies were shown to be
      specifically reactive to OprF by immunoblotting. The immunoglobulin G (IgG)
      immune response was predominantly of the IgG1 isotype. Sera from DNA vaccine
      immunized mice had significantly greater opsonic activity in opsonophagocytic
      assays than did sera from control mice. Following the initial immunization and
      two consecutive boosts, each at 2-week intervals, protection was demonstrated in
      a mouse model of chronic pulmonary infection by P. aeruginosa. Eight days
      postchallenge, both lungs were removed and examined. A significant reduction in
      the presence of severe macroscopic lesions, as well as in the number of bacteria
      present in the lungs, was seen. Based on these findings, genetic immunization
      with oprF has potential for development as a vaccine to protect humans against
      infection by P. aeruginosa.

PMID- 11292788
TI  - Selection for urease activity during Helicobacter pylori infection of rhesus
      macaques (Macaca mulatta).
AB  - Helicobacter pylori strain J166 recovered from experimentally inoculated rhesus
      monkeys had up to a 250-fold-increased urease activity over that before
      inoculation. This was found to result from the selection of urease positive J166
      clones from a heterogeneous inoculum, which was predominantly urease negative due
      to a 1-bp insertion in the ureA gene. These results confirm the importance of
      urease for H. pylori colonization. Strain J166 is particularly well adapted to
      the rhesus monkey, since it colonized preferentially despite the fact that less
      than 0.1% of the inoculum was urease positive.

PMID- 11292789
TI  - Characterization of the Plesiomonas shigelloides genes encoding the heme iron
      utilization system.
AB  - Plesiomonas shigelloides is a gram-negative pathogen which can utilize heme as an
      iron source. In previous work, P. shigelloides genes which permitted heme iron
      utilization in a laboratory strain of Escherichia coli were isolated. In the
      present study, the cloned P. shigelloides sequences were found to encode ten
      potential heme utilization proteins: HugA, the putative heme receptor; TonB and
      ExbBD; HugB, the putative periplasmic binding protein; HugCD, the putative inner
      membrane permease; and the proteins HugW, HugX, and HugZ. Three of the genes,
      hugA, hugZ, and tonB, contain a Fur box in their putative promoters, indicating
      that the genes may be iron regulated. When the P. shigelloides genes were tested
      in E. coli K-12 or in a heme iron utilization mutant of P. shigelloides, hugA,
      the TonB system genes, and hugW, hugX, or hugZ were required for heme iron
      utilization. When the genes were tested in a hemA entB mutant of E. coli, hugWXZ
      were not required for utilization of heme as a porphyrin source, but their
      absence resulted in heme toxicity when the strains were grown in media containing
      heme as an iron source. hugA could replace the Vibrio cholerae hutA in a heme
      iron utilization assay, and V. cholerae hutA could complement a P. shigelloides
      heme utilization mutant, suggesting that HugA is the heme receptor. Our analyses
      of the TonB system of P. shigelloides indicated that it could function in tonB
      mutants of both E. coli and V. cholerae and that it was similar to the V.
      cholerae TonB1 system in the amino acid sequence of the proteins and in the
      ability of the system to function in high-salt medium.

PMID- 11292790
TI  - Streptococcus salivarius fimbriae are composed of a glycoprotein containing a
      repeated motif assembled into a filamentous nondissociable structure.
AB  - Streptococcus salivarius, a gram-positive bacterium found in the human oral
      cavity, expresses flexible peritrichous fimbriae. In this paper, we report
      purification and partial characterization of S. salivarius fimbriae. Fimbriae
      were extracted by shearing the cell surface of hyperfimbriated mutant A37 (a
      spontaneous mutant of S. salivarius ATCC 25975) with glass beads. Preliminary
      experiments showed that S. salivarius fimbriae did not dissociate when they were
      incubated at 100 degrees C in the presence of sodium dodecyl sulfate. This
      characteristic was used to separate them from other cell surface components by
      successive gel filtration chromatography procedures. Fimbriae with molecular
      masses ranging from 20 x 10(6) to 40 x 10(6) Da were purified. Examination of
      purified fimbriae by electron microscopy revealed the presence of filamentous
      structures up to 1 microm long and 3 to 4 nm in diameter. Biochemical studies of
      purified fimbriae and an amino acid sequence analysis of a fimbrial internal
      peptide revealed that S. salivarius fimbriae were composed of a glycoprotein
      assembled into a filamentous structure resistant to dissociation. The internal
      amino acid sequence was composed of a repeated motif of two amino acids
      alternating with two modified residues: A/X/T-E-Q-M/phi, where X represents a
      modified amino acid residue and phi represents a blank cycle. Immunolocalization
      experiments also revealed that the fimbriae were associated with a wheat germ
      agglutinin-reactive carbohydrate. Immunolabeling experiments with antifimbria
      polyclonal antibodies showed that antigenically related fimbria-like structures
      were expressed in two other human oral streptococcal species, Streptococcus mitis
      and Streptococcus constellatus.

PMID- 11292791
TI  - Roles of hilC and hilD in regulation of hilA expression in Salmonella enterica
      serovar Typhimurium.
AB  - Sequences between -332 and -39 upstream of the hilA promoter are required for
      repression of hilA. An unidentified repressor is thought to bind these upstream
      repressing sequences (URS) to inhibit hilA expression. Two AraC-like
      transcriptional regulators encoded on Salmonella pathogenicity island 1 (SPI1),
      HilC and HilD, bind to the URS to counteract the repression of hilA. The URS is
      required for regulation of hilA by osmolarity, oxygen, PhoP/PhoQ, and SirA/BarA.
      Here, we show that FadD, FliZ, PhoB, and EnvZ/OmpR also require the URS to
      regulate hilA. These environmental and regulatory factors may affect hilA
      expression by altering the expression or activity of HilC, HilD, or the unknown
      repressor. To begin investigating these possibilities, we tested the effects of
      environmental and regulatory factors on hilC and hilD expression. We also
      examined hilA regulation when hilC or hilD was disrupted or expressed to a high
      level. Although hilC is regulated by all environmental conditions and regulatory
      factors that modulate hilA expression, hilC is not required for the regulation of
      hilA by any conditions or factors except EnvZ/OmpR. In contrast, hilD is
      absolutely required for hilA expression, but environmental conditions and
      regulatory factors have little or no effect on hilD expression. We speculate that
      EnvZ/OmpR regulates hilA by altering the expression and/or activity of hilC,
      while all other regulatory conditions and mutations regulate hilA by modulating
      hilD posttranscriptionally. We also discuss models in which the regulation of
      hilA expression is mediated by modulation of the expression or activity of one or
      more repressors.

PMID- 11292792
TI  - The ToxR-mediated organic acid tolerance response of Vibrio cholerae requires
      OmpU.
AB  - It was previously demonstrated that the intestinal pathogen Vibrio cholerae could
      undergo an adaptive stress response known as the acid tolerance response (ATR).
      The ATR is subdivided into two branches, inorganic ATR and organic ATR. The
      transcriptional regulator ToxR, while not involved in inorganic ATR, is required
      for organic ATR in a ToxT-independent manner. Herein, we investigate the effect
      of organic acid stress on global protein synthesis in V. cholerae and show by two
      dimensional gel electrophoresis that the stress response alters the expression of
      more than 100 polypeptide species. The expression of more than 20 polypeptide
      species is altered in a toxR strain compared to the wild type. Despite this,
      ectopic expression of the porin OmpU from an inducible promoter is shown to be
      sufficient to bypass the toxR organic ATR defect. Characterization of the effect
      of organic acid stress on ompU and ompT transcription reveals that while ompU
      transcription remains virtually unaffected, ompT transcription is repressed in a
      ToxR-independent manner. These transcript levels are similarly reflected in the
      extent of accumulation of OmpU and OmpT. Possible roles for OmpU in organic acid
      resistance are discussed.

PMID- 11292793
TI  - Characterization of in vitro interactions between a truncated TonB protein from
      Escherichia coli and the outer membrane receptors FhuA and FepA.
AB  - High-affinity iron uptake in gram-negative bacteria depends upon TonB, a protein
      which couples the proton motive force in the cytoplasmic membrane to iron chelate
      receptors in the outer membrane. To advance studies on TonB structure and
      function, we expressed a recombinant form of Escherichia coli TonB lacking the N
      terminal cytoplasmic membrane anchor. This protein (H(6)-'TonB; M(r), 24,880) was
      isolated in a soluble fraction of lysed cells and was purified by virtue of a
      hexahistidine tag located at its N terminus. Sedimentation experiments indicated
      that the H(6)-'TonB preparation was almost monodisperse and the protein was
      essentially monomeric. The value found for the Stokes radius (3.8 nm) is in good
      agreement with the value calculated by size exclusion chromatography. The
      frictional ratio (2.0) suggested that H(6)-'TonB adopts a highly asymmetrical
      form with an axial ratio of 15. H(6)-'TonB captured both the ferrichrome-iron
      receptor FhuA and the ferric enterobactin receptor FepA from detergent
      solubilized outer membranes in vitro. Capture was enhanced by preincubation of
      the receptors with their cognate ligands. Cross-linking assays with the purified
      proteins in vitro demonstrated that there was preferential interaction between
      TonB and ligand-loaded FhuA. Purified H(6)-'TonB was found to be stable and thus
      shows promise for high-resolution structural studies.

PMID- 11292794
TI  - Escherichia coli ribosome-associated protein SRA, whose copy number increases
      during stationary phase.
AB  - Protein D has previously been demonstrated to be associated with Escherichia coli
      ribosomes by the radical-free and highly reducing method of two-dimensional
      polyacrylamide gel electrophoresis. In this study, we show that protein D is
      exclusively present in the 30S ribosomal subunit and that its gene is located at
      33.6 min on the E. coli genetic map, between ompC and sfcA. The gene consists of
      45 codons, coding for a protein of 5,096 Da. The copy number of protein D per
      ribosomal particle varied during growth and increased from 0.1 in the exponential
      phase to 0.4 in the stationary phase. For these reasons, protein D was named SRA
      (stationary-phase-induced ribosome-associated) protein and its gene was named
      sra. The amount of SRA protein within the cell was found to be controlled mainly
      at the transcriptional level: its transcription increased rapidly upon entry into
      the stationary phase and was partly dependent on an alternative sigma factor
      (sigma S). In addition, global regulators, such as factor inversion stimulation
      (FIS), integration host factor (IHF), cyclic AMP, and ppGpp, were found to play a
      role either directly or indirectly in the transcription of sra in the stationary
      phase.

PMID- 11292795
TI  - Identification of yacE (coaE) as the structural gene for dephosphocoenzyme A
      kinase in Escherichia coli K-12.
AB  - Dephosphocoenzyme A (dephospho-CoA) kinase catalyzes the final step in coenzyme A
      biosynthesis, the phosphorylation of the 3'-hydroxy group of the ribose sugar
      moiety. Wild-type dephospho-CoA kinase from Corynebacterium ammoniagenes was
      purified to homogeneity and subjected to N-terminal sequence analysis. A BLAST
      search identified a gene from Escherichia coli previously designated yacE
      encoding a highly homologous protein. Amplification of the gene and
      overexpression yielded recombinant dephospho-CoA kinase as a 22.6-kDa monomer.
      Enzyme assay and nuclear magnetic resonance analyses of the product demonstrated
      that the recombinant enzyme is indeed dephospho-CoA kinase. The activities with
      adenosine, AMP, and adenosine phosphosulfate were 4 to 8% of the activity with
      dephospho-CoA. Homologues of the E. coli dephospho-CoA kinase were identified in
      a diverse range of organisms.

PMID- 11292796
TI  - Genes essential to iron transport in the cyanobacterium Synechocystis sp. strain
      PCC 6803.
AB  - Genes encoding polypeptides of an ATP binding cassette (ABC)-type ferric iron
      transporter that plays a major role in iron acquisition in Synechocystis sp.
      strain PCC 6803 were identified. These genes are slr1295, slr0513, slr0327, and
      recently reported sll1878 (Katoh et al., J. Bacteriol. 182:6523-6524, 2000) and
      were designated futA1, futA2, futB, and futC, respectively, for their involvement
      in ferric iron uptake. Inactivation of these genes individually or futA1 and
      futA2 together greatly reduced the activity of ferric iron uptake in cells grown
      in complete medium or iron-deprived medium. All the fut genes are expressed in
      cells grown in complete medium, and expression was enhanced by iron starvation.
      The futA1 and futA2 genes appear to encode periplasmic proteins that play a
      redundant role in iron binding. The deduced products of futB and futC genes
      contain nucleotide-binding motifs and belong to the ABC transporter family of
      inner-membrane-bound and membrane-associated proteins, respectively. These
      results and sequence similarities among the four genes suggest that the Fut
      system is related to the Sfu/Fbp family of iron transporters. Inactivation of
      slr1392, a homologue of feoB in Escherichia coli, greatly reduced the activity of
      ferrous iron transport. This system is induced by intracellular low iron
      concentrations that are achieved in cells exposed to iron-free medium or in the
      fut-less mutants grown in complete medium.

PMID- 11292798
TI  - Dissection of the functional and structural domains of phosphorelay histidine
      kinase A of Bacillus subtilis.
AB  - The initiation of sporulation in Bacillus subtilis results primarily from
      phosphoryl group input into the phosphorelay by histidine kinases, the major
      kinase being kinase A. Kinase A is active as a homodimer, the protomer of which
      consists of an approximately 400-amino-acid N-terminal putative signal-sensing
      region and a 200-amino-acid C-terminal autokinase. On the basis of sequence
      similarity, the N-terminal region may be subdivided into three PAS domains: A, B,
      and C, located from the N- to the C-terminal end. Proteolysis experiments and two
      hybrid analyses indicated that dimerization of the N-terminal region is
      accomplished through the PAS-B/PAS-C region of the molecule, whereas the most
      amino-proximal PAS-A domain is not dimerized. N-terminal deletions generated with
      maltose binding fusion proteins showed that an intact PAS-A domain is very
      important for enzymatic activity. Amino acid substitution mutations in PAS-A as
      well as PAS-C affected the in vivo activity of kinase A, suggesting that both PAS
      domains are required for signal sensing. The C-terminal autokinase, when produced
      without the N-terminal region, was a dimer, probably because of the dimerization
      required for formation of the four-helix-bundle phosphotransferase domain. The
      truncated autokinase was virtually inactive in autophosphorylation with ATP,
      whereas phosphorylation of the histidine of the phosphotransfer domain by back
      reactions from Spo0F~P appeared normal. The phosphorylated autokinase lost the
      ability to transfer its phosphoryl group to ADP, however. The N-terminal region
      appears to be essential both for signal sensing and for maintaining the correct
      conformation of the autokinase component domains.

PMID- 11292797
TI  - The pyrimidine operon pyrRPB-carA from Lactococcus lactis.
AB  - The four genes pyrR, pyrP, pyrB, and carA were found to constitute an operon in
      Lactococcus lactis subsp. lactis MG1363. The functions of the different genes
      were established by mutational analysis. The first gene in the operon is the
      pyrimidine regulatory gene, pyrR, which is responsible for the regulation of the
      expression of the pyrimidine biosynthetic genes leading to UMP formation. The
      second gene encodes a membrane-bound high-affinity uracil permease, required for
      utilization of exogenous uracil. The last two genes in the operon, pyrB and carA,
      encode pyrimidine biosynthetic enzymes; aspartate transcarbamoylase (pyrB) is the
      second enzyme in the pathway, whereas carbamoyl-phosphate synthetase subunit A
      (carA) is the small subunit of a heterodimeric enzyme, catalyzing the formation
      of carbamoyl phosphate. The carA gene product is shown to be required for both
      pyrimidine and arginine biosynthesis. The expression of the pyrimidine
      biosynthetic genes including the pyrRPB-carA operon is subject to control at the
      transcriptional level, most probably by an attenuator mechanism in which PyrR
      acts as the regulatory protein.

PMID- 11292799
TI  - NreB from Achromobacter xylosoxidans 31A Is a nickel-induced transporter
      conferring nickel resistance.
AB  - There are two distinct nickel resistance loci on plasmid pTOM9 from Achromobacter
      xylosoxidans 31A, ncc and nre. Expression of the nreB gene was specifically
      induced by nickel and conferred nickel resistance on both A. xylosoxidans 31A and
      Escherichia coli. E. coli cells expressing nreB showed reduced accumulation of
      Ni(2+), suggesting that NreB mediated nickel efflux. The histidine-rich C
      terminal region of NreB was not essential but contributed to maximal Ni(2+)
      resistance.

PMID- 11292801
TI  - Interplay between the specific chaperone-like proteins HybG and HypC in
      maturation of hydrogenases 1, 2, and 3 from Escherichia coli.
AB  - The hybG gene product from Escherichia coli has been identified as a chaperone
      like protein acting in the maturation of hydrogenases 1 and 2. It was shown that
      HybG forms a complex with the precursor of the large subunit of hydrogenase 2. As
      with HypC, which is the chaperone-like protein involved in hydrogenase 3
      maturation, the N-terminal cysteine residue is crucial for complex formation.
      Introduction of a deletion into hybG abolished the generation of active
      hydrogenase 2 but only quantitatively reduced hydrogenase 1 activity since HypC
      could replace HybG in this function. In contrast, HybG could not take over the
      role of HypC in a DeltahypC genetic background. Overproduction of HybG,
      especially of the variants with the replaced N-terminal cysteine residue,
      strongly interfered with hydrogenase 3 maturation, apparently by titrating some
      other component(s) of the maturation machinery. The results indicate that the
      three hydrogenase isoenzymes not only are interacting at the functional level but
      are also interconnected during the maturation process.

PMID- 11292800
TI  - Selective mRNA degradation by polynucleotide phosphorylase in cold shock
      adaptation in Escherichia coli.
AB  - Upon cold shock, Escherichia coli cell growth transiently stops. During this
      acclimation phase, specific cold shock proteins (CSPs) are highly induced. At the
      end of the acclimation phase, their synthesis is reduced to new basal levels,
      while the non-cold shock protein synthesis is resumed, resulting in cell growth
      reinitiation. Here, we report that polynucleotide phosphorylase (PNPase) is
      required to repress CSP production at the end of the acclimation phase. A pnp
      mutant, upon cold shock, maintained a high level of CSPs even after 24 h. PNPase
      was found to be essential for selective degradation of CSP mRNAs at 15 degrees C.
      In a poly(A) polymerase mutant and a CsdA RNA helicase mutant, CSP expression
      upon cold shock was significantly prolonged, indicating that PNPase in concert
      with poly(A) polymerase and CsdA RNA helicase plays a critical role in cold shock
      adaptation.

PMID- 11292803
TI  - Mechanisms causing rapid and parallel losses of ribose catabolism in evolving
      populations of Escherichia coli B.
AB  - Twelve populations of Escherichia coli B all lost D-ribose catabolic function
      during 2,000 generations of evolution in glucose minimal medium. We sought to
      identify the population genetic processes and molecular genetic events that
      caused these rapid and parallel losses. Seven independent Rbs(-) mutants were
      isolated, and their competitive fitnesses were measured relative to that of their
      Rbs(+) progenitor. These Rbs(-) mutants were all about 1 to 2% more fit than the
      progenitor. A fluctuation test revealed an unusually high rate, about 5 x 10(-5)
      per cell generation, of mutation from Rbs(+) to Rbs(-), which contributed to
      rapid fixation. At the molecular level, the loss of ribose catabolic function
      involved the deletion of part or all of the ribose operon (rbs genes). The
      physical extent of the deletion varied between mutants, but each deletion was
      associated with an IS150 element located immediately upstream of the rbs operon.
      The deletions apparently involved transposition into various locations within the
      rbs operon; recombination between the new IS150 copy and the one upstream of the
      rbs operon then led to the deletion of the intervening sequence. To confirm that
      the beneficial fitness effect was caused by deletion of the rbs operon (and not
      some undetected mutation elsewhere), we used P1 transduction to restore the
      functional rbs operon to two Rbs(-) mutants, and we constructed another Rbs(-)
      strain by gene replacement with a deletion not involving IS150. All three of
      these new constructs confirmed that Rbs(-) mutants have a competitive advantage
      relative to their Rbs(+) counterparts in glucose minimal medium. The rapid and
      parallel evolutionary losses of ribose catabolic function thus involved both (i)
      an unusually high mutation rate, such that Rbs(-) mutants appeared repeatedly in
      all populations, and (ii) a selective advantage in glucose minimal medium that
      drove these mutants to fixation.

PMID- 11292802
TI  - Transcriptional regulation of the orf19 gene and the tir-cesT-eae operon of
      enteropathogenic Escherichia coli.
AB  - To establish an intimate interaction with the host epithelial cell surface,
      enteropathogenic Escherichia coli (EPEC) produces Tir, a bacterial protein that
      upon translocation and insertion into the epithelial cell membrane constitutes
      the receptor for intimin. The tir gene is encoded by the locus for enterocyte
      effacement (LEE), where it is flanked upstream by orf19 and downstream by the
      cesT and eae genes. With the use of a series of cat transcriptional fusions and
      primer extension analysis, we confirmed that tir, cesT, and eae form the LEE5
      operon, which is under the control of a promoter located upstream from tir, and
      found that the orf19 gene is transcribed as a monocistronic unit. We also
      demonstrated that the LEE-encoded regulator Ler was required for efficient
      activation of both the tir and the orf19 promoters and that a sequence motif
      located between positions -204 and -157 was needed for the Ler-dependent
      activation of the tir operon. Sequence elements located between positions -204
      and -97 were determined to be required for the differential negative modulatory
      effects exerted by unknown regulatory factors under specific growth conditions.
      Upon deletion of the upstream sequences, the tir promoter was fully active even
      in the absence of Ler, indicating that tir expression is subject to a repression
      mechanism that is counteracted by this regulatory protein. However, its full
      activation was still repressed by growth in rich medium or at 25 degrees C,
      suggesting that negative regulation also occurs at or downstream of the promoter.
      Expression of orf19, but not of the tir operon, became Ler independent in an hns
      mutant strain, suggesting that Ler overcomes the repression exerted by H-NS
      (histone-like nucleoid structuring protein) on this gene.

PMID- 11292804
TI  - In vivo and in vitro effects of integration host factor at the DmpR-regulated
      sigma(54)-dependent Po promoter.
AB  - Transcription from the Pseudomonas CF600-derived sigma(54)-dependent promoter Po
      is controlled by the aromatic-responsive activator DmpR. Here we examine the
      mechanism(s) by which integration host factor (IHF) stimulates DmpR-activated
      transcriptional output of the Po promoter both in vivo and in vitro. In vivo, the
      Po promoter exhibits characteristics that typify many sigma(54)-dependent
      promoters, namely, a phasing-dependent tolerance with respect to the distance
      from the regulator binding sites to the distally located RNA polymerase binding
      site, and a strong dependence on IHF for optimal promoter output. IHF is shown to
      affect transcription via structural repercussions mediated through binding to a
      single DNA signature located between the regulator and RNA polymerase binding
      sites. In vitro, using DNA templates that lack the regulator binding sites and
      thus bypass a role of IHF in facilitating physical interaction between the
      regulator and the transcriptional apparatus, IHF still mediates a DNA binding
      dependent stimulation of Po transcription. This stimulatory effect is shown to be
      independent of previously described mechanisms for the effects of IHF at
      sigma(54) promoters such as aiding binding of the regulator or recruitment of
      sigma(54)-RNA polymerase via UP element-like DNA. The effect of IHF could be
      traced to promotion and/or stabilization of open complexes within the
      nucleoprotein complex that may involve an A+T-rich region of the IHF binding site
      and promoter-upstream DNA. Mechanistic implications are discussed in the context
      of a model in which IHF binding results in transduction of DNA instability from
      an A+T-rich region to the melt region of the promoter.

PMID- 11292805
TI  - Low-molecular-weight plasmid of Salmonella enterica serovar Enteritidis codes for
      retron reverse transcriptase and influences phage resistance.
AB  - Retron reverse transcriptases are unusual procaryotic enzymes capable of
      synthesis of low-molecular-weight DNA by reverse transcription. All of the so-far
      described DNA species synthesized by retron reverse transcriptases have been
      identified as multicopy single-stranded DNA. We have shown that Salmonella
      enterica serovar Enteritidis is also capable of synthesis of the low-molecular
      weight DNA by retron reverse transcriptase. Surprisingly, Salmonella serovar
      Enteritidis-produced low-molecular-weight DNA was shown to be a double-stranded
      DNA with single-stranded overhangs (sdsDNA). The sdsDNA was 72 nucleotides (nt)
      long, of which a 38-nt sequence was formed by double-stranded DNA with 19- and 15
      nt single-stranded overhangs, respectively. Three open reading frames (ORFs),
      encoded by the 4,053-bp plasmid, were essential for the production of sdsDNA.
      These included an ORF with an unknown function, the retron reverse transcriptase,
      and an ORF encoding the cold shock protein homologue. This plasmid was also able
      to confer phage resistance onto the host cell by a mechanism which was
      independent of sdsDNA synthesis.

PMID- 11292806
TI  - Isogenic strain construction and gene targeting in Candida dubliniensis.
AB  - Candida dubliniensis is a recently described opportunistic fungal pathogen that
      is closely related to Candida albicans but differs from it with respect to
      epidemiology, certain virulence characteristics, and the ability to develop
      fluconazole resistance in vitro. A comparison of C. albicans and C. dubliniensis
      at the molecular level should therefore provide clues about the mechanisms used
      by these two species to adapt to their human host. In contrast to C. albicans, no
      auxotrophic C. dubliniensis strains are available for genetic manipulations.
      Therefore, we constructed homozygous ura3 mutants from a C. dubliniensis wild
      type isolate by targeted gene deletion. The two URA3 alleles were sequentially
      inactivated using the MPA(R)-flipping strategy, which is based on the selection
      of integrative transformants carrying a mycophenolic acid resistance marker that
      is subsequently deleted again by site-specific, FLP-mediated recombination. The
      URA3 gene from C. albicans (CaURA3) was then used as a selection marker for
      targeted integration of a fusion between the C. dubliniensis MDR1 (CdMDR1)
      promoter and a C. albicans-adapted GFP reporter gene. Uridine-prototrophic
      transformants were obtained with high frequency, and all transformants of two
      independent ura3-negative parent strains had correctly integrated the reporter
      gene fusion into the CdMDR1 locus, demonstrating that the CaURA3 gene can be used
      for efficient and specific targeting of recombinant DNA into the C. dubliniensis
      genome. Transformants carrying the reporter gene fusion did not exhibit
      detectable fluorescence during growth in yeast extract-peptone-dextrose medium in
      vitro, suggesting that CdMDR1 is not significantly expressed under these
      conditions. Fluconazole had no effect on MDR1 expression, but the addition of the
      drug benomyl strongly activated the reporter gene fusion in a dose-dependent
      fashion, demonstrating that the CdMDR1 gene, which encodes an efflux pump
      mediating resistance to toxic compounds, is induced by the presence of certain
      drugs.

PMID- 11292807
TI  - Function-based selection and characterization of base-pair polymorphisms in a
      promoter of Escherichia coli RNA polymerase-sigma(70).
AB  - We performed two sets of in vitro selections to dissect the role of the -10 base
      sequence in determining the rate and efficiency with which Escherichia coli RNA
      polymerase-sigma(70) forms stable complexes with a promoter. We identified
      sequences that (i) rapidly form heparin-resistant complexes with RNA polymerase
      or (ii) form heparin-resistant complexes at very low RNA polymerase
      concentrations. The sequences selected under the two conditions differ from each
      other and from the consensus -10 sequence. The selected promoters have the
      expected enhanced binding and kinetic properties and are functionally better than
      the consensus promoter sequence in directing RNA synthesis in vitro. Detailed
      analysis of the selected promoter functions shows that each step in this
      multistep pathway may have different sequence requirements, meaning that the
      sequence of a strong promoter does not contain the optimal sequence for each step
      but instead is a compromise sequence that allows all steps to proceed with
      minimal constraint.

PMID- 11292808
TI  - Interaction of alpha-agglutinin and a-agglutinin, Saccharomyces cerevisiae sexual
      cell adhesion molecules.
AB  - alpha-Agglutinin and a-agglutinin are complementary cell adhesion glycoproteins
      active during mating in the yeast Saccharomyces cerevisiae. They bind with high
      affinity and high specificity: cells of opposite mating types are irreversibly
      bound by a few pairs of agglutinins. Equilibrium and surface plasmon resonance
      kinetic analyses showed that the purified binding region of alpha-agglutinin
      interacted similarly with purified a-agglutinin and with a-agglutinin expressed
      on cell surfaces. At 20 degrees C, the K(D) for the interaction was 2 x 10(-9) to
      5 x 10(-9) M. This high affinity was a result of a very low dissociation rate (
      approximately 2.6 x 10(-4) s(-1)) coupled with a low association rate (= 5 x
      10(4) M(-1) s(-1)). Circular-dichroism spectroscopy showed that binding of the
      proteins was accompanied by measurable changes in secondary structure.
      Furthermore, when binding was assessed at 10 degrees C, the association kinetics
      were sigmoidal, with a very low initial rate. An induced-fit model of binding
      with substantial apposition of hydrophobic surfaces on the two ligands can
      explain the observed affinity, kinetics, and specificity and the conformational
      effects of the binding reaction.

PMID- 11292809
TI  - Reciprocal regulation of anaerobic and aerobic cell wall mannoprotein gene
      expression in Saccharomyces cerevisiae.
AB  - The DAN/TIR genes encode nine cell wall mannoproteins in Saccharomyces cerevisiae
      which are expressed during anaerobiosis (DAN1, DAN2, DAN3, DAN4, TIR1, TIR2,
      TIR3, TIR4, and TIP1). Most are expressed within an hour of an anaerobic shift,
      but DAN2 and DAN3 are expressed after about 3 h. At the same time, CWP1 and CWP2,
      the genes encoding the major mannoproteins, are down-regulated, suggesting that
      there is a programmed remodeling of the cell wall in which Cwp1 and Cwp2 are
      replaced by nine anaerobic counterparts. TIP1, TIR1, TIR2, and TIR4 are also
      induced during cold shock. Correspondingly, CWP1 is down-regulated during cold
      shock. As reported elsewhere, Mox4 is a heme-inhibited activator, and Mot3 is a
      heme-induced repressor of the DAN/TIR genes (but not of TIP1). We show that CWP2
      (but not CWP1) is controlled by the same factors, but in reverse fashion
      primarily by Mot3 (which can function as either an activator or repressor) but
      also by Mox4, accounting for the reciprocal regulation of the two groups of
      genes. Disruptions of TIR1, TIR3, or TIR4 prevent anaerobic growth, indicating
      that each protein is essential for anaerobic adaptation. The Dan/Tir and Cwp
      proteins are homologous, with the greatest similarities shown within three
      subgroups: the Dan proteins, the Tip and Tir proteins, and, more distantly, the
      Cwp proteins. The clustering of homology corresponds to differences in
      expression: the Tip and Tir proteins are expressed during hypoxia and cold shock,
      the Dan proteins are more stringently repressed by oxygen and insensitive to cold
      shock, and the Cwp proteins are oppositely regulated by oxygen and temperature.

PMID- 11292810
TI  - Bap, a Staphylococcus aureus surface protein involved in biofilm formation.
AB  - Identification of new genes involved in biofilm formation is needed to understand
      the molecular basis of strain variation and the pathogenic mechanisms implicated
      in chronic staphylococcal infections. A biofilm-producing Staphylococcus aureus
      isolate was used to generate biofilm-negative transposon (Tn917) insertion
      mutants. Two mutants were found with a significant decrease in attachment to
      inert surfaces (early adherence), intercellular adhesion, and biofilm formation.
      The transposon was inserted at the same locus in both mutants. This locus (bap
      [for biofilm associated protein]) encodes a novel cell wall associated protein of
      2,276 amino acids (Bap), which shows global organizational similarities to
      surface proteins of gram-negative (Pseudomonas aeruginosa and Salmonella enterica
      serovar Typhi) and gram-positive (Enteroccocus faecalis) microorganisms. Bap's
      core region represents 52% of the protein and consists of 13 successive nearly
      identical repeats, each containing 86 amino acids. bap was present in a small
      fraction of bovine mastitis isolates (5% of the 350 S. aureus isolates tested),
      but it was absent from the 75 clinical human S. aureus isolates analyzed. All
      staphylococcal isolates harboring bap were highly adherent and strong biofilm
      producers. In a mouse infection model bap was involved in pathogenesis, causing a
      persistent infection.

PMID- 11292811
TI  - Genetic interactions between the Escherichia coli umuDC gene products and the
      beta processivity clamp of the replicative DNA polymerase.
AB  - The Escherichia coli umuDC gene products encode DNA polymerase V, which
      participates in both translesion DNA synthesis (TLS) and a DNA damage checkpoint
      control. These two temporally distinct roles of the umuDC gene products are
      regulated by RecA-single-stranded DNA-facilitated self-cleavage of UmuD (which
      participates in the checkpoint control) to yield UmuD' (which enables TLS). In
      addition, even modest overexpression of the umuDC gene products leads to a cold
      sensitive growth phenotype, apparently due to the inappropriate expression of the
      DNA damage checkpoint control activity of UmuD(2)C. We have previously reported
      that overexpression of the epsilon proofreading subunit of DNA polymerase III
      suppresses umuDC-mediated cold sensitivity, suggesting that interaction of
      epsilon with UmuD(2)C is important for the DNA damage checkpoint control function
      of the umuDC gene products. Here, we report that overexpression of the beta
      processivity clamp of the E. coli replicative DNA polymerase (encoded by the dnaN
      gene) not only exacerbates the cold sensitivity conferred by elevated levels of
      the umuDC gene products but, in addition, confers a severe cold-sensitive
      phenotype upon a strain expressing moderately elevated levels of the umuD'C gene
      products. Such a strain is not otherwise normally cold sensitive. To identify
      mutant beta proteins possibly deficient for physical interactions with the umuDC
      gene products, we selected for novel dnaN alleles unable to confer a cold
      sensitive growth phenotype upon a umuD'C-overexpressing strain. In all, we
      identified 75 dnaN alleles, 62 of which either reduced the expression of beta or
      prematurely truncated its synthesis, while the remaining alleles defined eight
      unique missense mutations of dnaN. Each of the dnaN missense mutations retained
      at least a partial ability to function in chromosomal DNA replication in vivo. In
      addition, these eight dnaN alleles were also unable to exacerbate the cold
      sensitivity conferred by modestly elevated levels of the umuDC gene products,
      suggesting that the interactions between UmuD' and beta are a subset of those
      between UmuD and beta. Taken together, these findings suggest that interaction of
      beta with UmuD(2)C is important for the DNA damage checkpoint function of the
      umuDC gene products. Four possible models for how interactions of UmuD(2)C with
      the epsilon and the beta subunits of DNA polymerase III might help to regulate
      DNA replication in response to DNA damage are discussed.

PMID- 11292812
TI  - Expression of the putative siderophore receptor gene bfrZ is controlled by the
      extracytoplasmic-function sigma factor BupI in Bordetella bronchiseptica.
AB  - A new gene from Bordetella bronchiseptica, bfrZ encoding a putative siderophore
      receptor, was identified in a Fur-repressor titration assay. A bfrZ null mutant
      was constructed by allelic exchange. The protein profile of this mutant is
      similar to that of the wild-type parent strain. The BfrZ(-)-BfrZ(+) isogenic pair
      was tested for utilization of 132 different siderophores as iron sources. None of
      these iron sources acted as a ligand for BfrZ. Translational bfrZ::phoA and
      transcriptional bfrZ::lacZ fusions were introduced into the B. bronchiseptica
      bfrZ locus. No alkaline phosphatase or beta-galactosidase activity was detected.
      Sequence analysis of the bfrZ upstream region revealed the presence of two
      tightly linked genes, bupI and bupR. Both of these genes are located downstream
      from a Fur-binding sequence. BupI is homologous to Escherichia coli FecI and
      Pseudomonas putida PupI and belongs to the family of extracytoplasmic-function
      sigma factors involved in transcription of genes with extracytoplasmic functions.
      BupR is homologous to the FecR and PupR antisigma factors and is predicted to be
      localized in the inner membrane. Similar to the surface signaling receptors FecA
      and PupB, BfrZ bears an N-terminal extension. We found that bfrZ is not
      transcribed when bupI and bupR are expressed at the same level. However,
      overexpression of bupI from a multicopy plasmid triggers bfrZ transcription, and
      under these conditions BfrZ was detected in membrane fractions. By analogy with
      the FecI-FecR-FecA and PupI-PupR-PupB systems, our data suggest that bfrZ
      expression is inducible by binding of the cognate ligand to BfrZ and transduction
      of a signal through the envelope.

PMID- 11292813
TI  - Mapping stress-induced changes in autoinducer AI-2 production in chemostat
      cultivated Escherichia coli K-12.
AB  - Numerous gram-negative bacteria employ a cell-to-cell signaling mechanism, termed
      quorum sensing, for controlling gene expression in response to population
      density. Recently, this phenomenon has been discovered in Escherichia coli, and
      while pathogenic E. coli utilize quorum sensing to regulate pathogenesis (i.e.,
      expression of virulence genes), the role of quorum sensing in nonpathogenic E.
      coli is less clear, and in particular, there is no information regarding the role
      of quorum sensing during the overexpression of recombinant proteins. The
      production of autoinducer AI-2, a signaling molecule employed by E. coli for
      intercellular communication, was studied in E. coli W3110 chemostat cultures
      using a Vibrio harveyi AI-2 reporter assay (M. G. Surrette and B. L. Bassler,
      Proc. Natl. Acad. Sci. USA 95:7046-7050, 1998). Chemostat cultures enabled a
      study of AI-2 regulation through steady-state and transient responses to a
      variety of environmental stimuli. Results demonstrated that AI-2 levels increased
      with the steady-state culture growth rate. In addition, AI-2 increased following
      pulsed addition of glucose, Fe(III), NaCl, and dithiothreitol and decreased
      following aerobiosis, amino acid starvation, and isopropyl-beta-D
      thiogalactopyranoside-induced expression of human interleukin-2 (hIL-2). In
      general, the AI-2 responses to several perturbations were indicative of a shift
      in metabolic activity or state of the cells induced by the individual stress.
      Because of our interest in the expression of heterologous proteins in E. coli,
      the transcription of four quorum-regulated genes and 20 stress genes was mapped
      during the transient response to induced expression of hIL-2. Significant
      regulatory overlap was revealed among several stress and starvation genes and
      known quorum-sensing genes.

PMID- 11292814
TI  - Characterization of the D-xylulose 5-phosphate/D-fructose 6-phosphate
      phosphoketolase gene (xfp) from Bifidobacterium lactis.
AB  - A D-xylulose 5-phosphate/D-fructose 6-phosphate phosphoketolase (Xfp) from the
      probiotic Bifidobacterium lactis was purified to homogeneity. The specific
      activity of the purified enzyme with D-fructose 6-phosphate as a substrate is
      4.28 Units per mg of enzyme. K(m) values for D-xylulose 5-phosphate and D
      fructose 6-phosphate are 45 and 10 mM, respectively. The native enzyme has a
      molecular mass of 550,000 Da. The subunit size upon sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (90,000 Da) corresponds with the size (92,529
      Da) calculated from the amino acid sequence of the isolated gene (named xfp)
      encoding 825 amino acids. The xfp gene was identified on the chromosome of B.
      lactis with the help of degenerated nucleotide probes deduced from the common N
      terminal amino acid sequence of both the native and denatured enzyme. Comparison
      of the deduced amino acid sequence of the cloned gene with sequences in public
      databases revealed high homologies with hypothetical proteins (26 to 55%
      identity) in 20 microbial genomes. The amino acid sequence derived from the xfp
      gene contains typical thiamine diphosphate (ThDP) binding sites reported for
      other ThDP-dependent enzymes. Two truncated putative genes, pta and guaA, were
      localized adjacent to xfp on the B. lactis chromosome coding for a
      phosphotransacetylase and a guanosine monophosphate synthetase homologous to
      products of genes in Mycobacterium tuberculosis. However, xfp is transcribed in
      B. lactis as a monocistronic operon. It is the first reported and sequenced gene
      of a phosphoketolase.

PMID- 11292816
TI  - Characterization of intragenic recombination in a hyperthermophilic archaeon via
      conjugational DNA exchange.
AB  - Sulfolobus acidocaldarius is so far the only hyperthermophilic archaeon in which
      genetic recombination can be assayed by conjugation and simple selections.
      Crosses among spontaneous pyr mutants were able to resolve closely spaced
      chromosomal mutations, identify deletions and rearrangements, and map mutations
      to a given deletion interval. Frameshift mutations in pyrE exerted polar effects
      that depressed orotidine-5'-monophosphate decarboxylase activity (encoded by
      pyrF), whereas base pair substitutions and an 18-bp deletion had no effect.

PMID- 11292815
TI  - Roles of rpoN, fliA, and flgR in expression of flagella in Campylobacter jejuni.
AB  - Three potential regulators of flagellar expression present in the genome sequence
      of Campylobacter jejuni NCTC 11168, the genes rpoN, flgR, and fliA, which encode
      the alternative sigma factor sigma(54), the sigma(54)-associated transcriptional
      activator FlgR, and the flagellar sigma factor sigma(28), respectively, were
      investigated for their role in global regulation of flagellar expression. The
      three genes were insertionally inactivated in C. jejuni strains NCTC 11168 and
      NCTC 11828. Electron microscopic studies of the wild-type and mutant strains
      showed that the rpoN and flgR mutants were nonflagellate and that the fliA mutant
      had truncated flagella. Immunoblotting experiments with the three mutants
      confirmed the roles of rpoN, flgR, and fliA in the expression of flagellin.

PMID- 11292817
TI  - Specific binding of integrase to the origin of transfer (oriT) of the conjugative
      transposon Tn916.
AB  - Purified integrase protein (Int) of the conjugative transposon Tn916 was shown,
      using nuclease protection experiments, to bind specifically to a site within the
      origin of conjugal transfer of the transposon, oriT. A sequence similar to the
      ends of the transposon that are bound by the C-terminal DNA-binding domain of Int
      was present in the protected region. However, Int binding to oriT required both
      the N- and C-terminal DNA-binding domains of Int, and the pattern of nuclease
      protection differed from that observed when Int binds to the transposon ends and
      flanking DNA. Binding of Int to oriT may be part of a mechanism to prevent
      premature conjugal transfer of Tn916 prior to excision from the donor DNA.

PMID- 11292818
TI  - Mapping of the Rsd contact site on the sigma 70 subunit of Escherichia coli RNA
      polymerase.
AB  - Rsd (regulator of sigma D) is an anti-sigma factor for the Escherichia coli RNA
      polymerase sigma(70) subunit. The contact site of Rsd on sigma(70) was analyzed
      after mapping of the contact-dependent cleavage sites by Rsd-tethered iron-p
      bromoacetamidobenzyl EDTA and by analysis of the complex formation between Ala
      substituted sigma(70) and Rsd. Results indicate that the Rsd contact site is
      located downstream of the promoter -35 recognition helix-turn-helix motif within
      region 4, overlapping with the regions involved in interaction with both core
      enzyme and sigma(70) contact transcription factors.

PMID- 11292819
TI  - Competence regulation by oxygen availability and by Nox is not related to
      specific adjustment of central metabolism in Streptococcus pneumoniae.
AB  - In Streptococcus pneumoniae oxygen availability is a major determinant for
      competence development in exponentially growing cultures. NADH oxidase activity
      is required for optimal competence in cultures grown aerobically. The implication
      of oxidative metabolism and more specifically of Nox on central metabolism has
      been examined. Glycolytic flux throughout exponential growth revealed homolactic
      fermentation with a lactate production/glucose utilization ratio close to 2,
      whatever the aerobiosis level of the culture. Loss-of-function mutations in nox,
      which encodes NADH oxidase, did not change this trait. Consistently, mRNA levels
      of glyceraldehyde-3-phosphate dehydrogenase, L-lactate dehydrogenase, pyruvate
      oxidase, and NADH oxidase remained comparable to wild-type levels, as did the
      specific activities of key enzymes which control central metabolism. Competence
      regulation by oxygen involving the NADH oxidase activity is not due to
      significant modification of carbon flux through glycolysis. Failure to obtain
      loss-of-function mutation in L-ldh, which encodes the L-lactate dehydrogenase,
      indicates its essential role in pneumococci whatever their growth status.

PMID- 11292821
TI  - Coordinated control of endothelial nitric-oxide synthase phosphorylation by
      protein kinase C and the cAMP-dependent protein kinase.
AB  - Endothelial nitric-oxide synthase (eNOS) is an important regulatory enzyme in the
      cardiovascular system catalyzing the production of NO from arginine. Multiple
      protein kinases including Akt/PKB, cAMP-dependent protein kinase (PKA), and the
      AMP-activated protein kinase (AMPK) activate eNOS by phosphorylating Ser-1177 in
      response to various stimuli. During VEGF signaling in endothelial cells, there is
      a transient increase in Ser-1177 phosphorylation coupled with a decrease in Thr
      495 phosphorylation that reverses over 10 min. PKC signaling in endothelial cells
      inhibits eNOS activity by phosphorylating Thr-495 and dephosphorylating Ser-1177
      whereas PKA signaling acts in reverse by increasing phosphorylation of Ser-1177
      and dephosphorylation of Thr-495 to activate eNOS. Both phosphatases PP1 and PP2A
      are associated with eNOS. PP1 is responsible for dephosphorylation of Thr-495
      based on its specificity for this site in both eNOS and the corresponding
      synthetic phosphopeptide whereas PP2A is responsible for dephosphorylation of Ser
      1177. Treatment of endothelial cells with calyculin selectively blocks PKA
      mediated dephosphorylation of Thr-495 whereas okadaic acid selectively blocks PKC
      mediated dephosphorylation of Ser-1177. These results show that regulation of
      eNOS activity involves coordinated signaling through Ser-1177 and Thr-495 by
      multiple protein kinases and phosphatases.

PMID- 11292820
TI  - Growth phase variation in cell and nucleoid morphology in a Bacillus subtilis
      recA mutant.
AB  - The major role of RecA is thought to be in helping repair and restart stalled
      replication forks. During exponential growth, Bacillus subtilis recA cells
      exhibited few microscopically observable nucleoid defects. However, the
      efficiency of plating was about 12% of that of the parent strain. A substantial
      and additive defect in viability was also seen for addB and recF mutants,
      suggesting a role for the corresponding recombination paths during normal growth.
      Upon entry into stationary phase, a subpopulation (approximately 15%) of
      abnormally long cells and nucleoids developed in B. subtilis recA mutants. In
      addition, recA mutants showed a delay in, and a diminished capacity for,
      effecting prespore nucleoid condensation.

PMID- 11292822
TI  - Probing fibroblast growth factor dimerization and role of heparin-like
      glycosaminoglycans in modulating dimerization and signaling.
AB  - For a number of growth factors and cytokines, ligand dimerization is believed to
      be central to the formation of an active signaling complex. In the case of
      fibroblast growth factor-2 (FGF2) signaling, heparin/heparan sulfate-like
      glycosaminoglycans (HLGAGs) are involved through interaction with both FGF2 and
      its receptors (FGFRs) in assembling a tertiary complex and modulating FGF2
      activity. Biochemical data have suggested different modes of HLGAG-induced FGF2
      dimerization involving specific protein-protein contacts. In addition, several
      recent x-ray crystallography studies of FGF.FGFR and FGF.FGFR.HLGAG complexes
      have revealed other modes of molecular assemblage, with no FGF-FGF contacts. All
      these different biochemical and structural findings have clarified less and in
      fact raised more questions as to which mode of FGF2 dimerization, if any, is
      essential for signaling. In this study, we address the issue of FGF2 dimerization
      in signaling using a combination of biochemical, biophysical, and site-directed
      mutagenesis approaches. Our findings presented here provide direct evidence of
      FGF2 dimerization in mediating FGF2 signaling.

PMID- 11292823
TI  - Vanadium-induced nuclear factor of activated T cells activation through hydrogen
      peroxide.
AB  - The present study investigated the role of reactive oxygen species (ROS) in
      activation of nuclear factor of activated T cells (NFAT), a pivotal transcription
      factor responsible for regulation of cytokines, by vanadium in mouse embryo
      fibroblast PW cells or mouse epidermal Cl 41 cells. Exposure of cells to vanadium
      led to the transactivation of NFAT in a time- and dose-dependent manner.
      Scavenging of vanadium-induced H(2)O(2) with N-acety-L-cyteine (a general
      antioxidant) or catalase (a specific H(2)O(2) inhibitor) or the chelation of
      vanadate with deferoxamine, resulted in inhibition of NFAT activation. In
      contrast, an increase in H(2)O(2) generation by the addition of superoxide
      dismutase or NADPH enhanced vanadium-induced NFAT activation. This vanadate
      mediated H(2)O(2) generation was verified by both electron spin resonance and
      fluorescence staining assay. These results demonstrate that H(2)O(2) plays an
      important role in vanadium-induced NFAT transactivation in two different cell
      types. Furthermore, pretreatment of cells with nifedipine, a calcium channel
      blocker, inhibited vanadium-induced NFAT activation, whereas and ionomycin, two
      calcium ionophores, had synergistic effects with vanadium for NFAT induction.
      Incubation of cells with cyclosporin A (CsA), a pharmacological inhibitor of the
      phosphatase calcineurin, blocked vanadium-induced NFAT activation. All data show
      that vanadium induces NFAT activation not only through a calcium-dependent and
      CsA-sensitive pathway but also involved H(2)O(2) generation, suggesting that
      H(2)O(2) may be involved in activation of calcium-calcineurin pathways for NFAT
      activation caused by vanadium exposure.

PMID- 11292824
TI  - Sustained activation of the extracellular signal-regulated kinase pathway is
      required for extracellular calcium stimulation of human osteoblast proliferation.
AB  - Elevated levels of [Ca(2+)](o) in bone milieu as a result of the resorptive
      action of osteoclasts are implicated in promoting proliferation and migration of
      osteoblasts during bone remodeling. However, mitogenic effects of [Ca(2+)](o)
      have only been shown in some, but not all, clonal osteoblast-like cells, and the
      molecular mechanisms underlying [Ca(2+)](o)-induced mitogenic signaling are
      largely unknown. In this study we demonstrated for the first time that
      [Ca(2+)](o) stimulated proliferation of primary human osteoblasts and selectively
      activated extracellular signal-regulated kinases (ERKs). Neither p38 mitogen
      activated protein (MAP) kinase nor stress-activated protein kinase was activated
      by [Ca(2+)](o). Treatment of human osteoblasts with a MAP kinase kinase
      inhibitor, PD98059, impaired both basal and [Ca(2+)](o)-stimulated
      phosphorylation of ERKs and also reduced both basal and [Ca(2+)](o)-stimulated
      proliferation. [Ca(2+)](o) treatment resulted in two distinctive phases of ERK
      activation: an acute phase and a sustained phase. An inhibition time course
      revealed that it was the sustained phase, not the acute phase, that was critical
      for [Ca(2+)](o)-stimulated osteoblast proliferation. Our results demonstrate that
      mitogenic responsiveness to [Ca(2+)](o) is present in primary human osteoblasts
      and is mediated via prolonged activation of the MAP kinase kinase/ERK signal
      pathway.

PMID- 11292826
TI  - Thermodynamics of Ras/effector and Cdc42/effector interactions probed by
      isothermal titration calorimetry.
AB  - Proliferation, differentiation, and morphology of eucaryotic cells is regulated
      by a large network of signaling molecules. Among the major players are members of
      the Ras and Rho/Rac subfamilies of small GTPases that bind to different sets of
      effector proteins. Recognition of multiple effectors is important for
      communicating signals into different pathways, leading to the question of how an
      individual GTPase achieves tight binding to diverse targets. To understand the
      observed specificity, detailed information about binding energetics is expected
      to complement the information gained from the three-dimensional structures of
      GTPase/effector protein complexes. Here, the thermodynamics of the interaction of
      four closely related members of the Ras subfamily with four different effectors
      and, additionally, the more distantly related Cdc42/WASP couple were quantified
      by means of isothermal titration calorimetry. The heat capacity changes upon
      complex formation were rationalized in light of the GTPase/effector complex
      structures. Changes in enthalpy, entropy, and heat capacity of association with
      various Ras proteins are similar for the same effector. In contrast, although the
      structures of the Ras-binding domains are similar, the thermodynamics of the
      Ras/Raf and Ras/Ral guanine nucleotide dissociation stimulator interactions are
      quite different. The energy profile of the Cdc42/WASP interaction is similar to
      Ras/Ral guanine nucleotide dissociation stimulator, despite largely different
      structures and interface areas of the complexes. Water molecules in the interface
      cannot fully account for the observed discrepancy but may explain the large range
      of Ras/effector binding specificity. The differences in the thermodynamic
      parameters, particularly the entropy changes, could help in the design of
      effector-specific inhibitors that selectively block a single pathway.

PMID- 11292827
TI  - Identification of a human orthologue of Sec34p as a component of the cis-Golgi
      vesicle tethering machinery.
AB  - The roles of the components of the Sec34p protein complex in intracellular
      membrane trafficking, first identified in the yeast Saccharomyces cerevisiae,
      have yet to be characterized in higher eukaryotes. We cloned a human cDNA whose
      predicted amino acid sequence showed 41% similarity to yeast Sec34p with homology
      throughout the entire coding region. Affinity-purified antibodies raised against
      the human SEC34 protein (hSec34p) recognized a cellular protein of 94 kDa in both
      soluble and membrane fractions. Like yeast Sec34p, cytosolic hSec34p migrated
      with an apparent molecular mass of 300 kDa on a glycerol velocity gradient,
      suggesting that it is part of a protein complex. Immunofluorescence microscopy
      localized hSec34p to the Golgi compartment in cells of all species examined,
      where it co-localized well with the cis/medial Golgi marker membrin and partially
      co-localized with cis-Golgi network marker p115 and trans-Golgi marker TGN38. The
      co-localization with membrin was maintained at 15 degrees C and after microtubule
      depolymerization with nocodazole. During transport of the tsO45 vesicular
      stomatitis virus G protein through the Golgi, there was significant overlap with
      the hSec34p compartment. Green fluorescent protein-hSec34 expressed in HeLa cells
      was restricted to Golgi cisternae, and its membrane association was sensitive to
      brefeldin A treatment. Taken together, our findings indicate that hSec34p is part
      of a peripheral membrane protein complex localized on cis/medial Golgi cisternae
      where it may participate in tethering intra-Golgi transport vesicles.

PMID- 11292825
TI  - Phosphorylation of RGS9-1 by an endogenous protein kinase in rod outer segments.
AB  - Inactivation of the visual G protein transducin, during recovery from
      photoexcitation, is regulated by RGS9-1, a GTPase-accelerating protein of the
      ubiquitous RGS protein family. Incubation of dark-adapted bovine rod outer
      segments with [gamma-(32)P]ATP led to RGS9-1 phosphorylation by an endogenous
      kinase in rod outer segment membranes, with an average stoichiometry of 0.2-0.45
      mol of phosphates/mol of RGS9-1. Mass spectrometry revealed a single major site
      of phosphorylation, Ser(475). The kinase responsible catalyzed robust
      phosphorylation of recombinant RGS9-1 and not of an S475A mutant. A synthetic
      peptide corresponding to the region surrounding Ser(475) was also phosphorylated,
      and a similar peptide with the S475A substitution inhibited RGS9-1
      phosphorylation. The RGS9-1 kinase is a peripheral membrane protein that co
      purifies with rhodopsin in sucrose gradients and can be extracted in buffers of
      high ionic strength. It is not inhibited or activated significantly by a panel of
      inhibitors or activators of protein kinase A, protein kinase G, rhodopsin kinase,
      CaM kinase II, casein kinase II, or cyclin-dependent kinase 5, at concentrations
      50 or more times higher than their reported IC(50) or K(i) values. It was
      inhibited by the protein kinase C inhibitor bisindolylmaleimide I and by lowering
      Ca(2+) to nanomolar levels with EGTA; however, it was not stimulated by the
      addition of phorbol ester, under conditions that significantly enhanced rhodopsin
      phosphorylation. A monoclonal antibody specific for the Ser(475)-phosphorylated
      form of RGS9-1 recognized RGS9-1 in immunoblots of dark-adapted mouse retina.
      Retinas from light-adapted mice had much lower levels of RGS9-1 phosphorylation.
      Thus, RGS9-1 is phosphorylated on Ser(475) in vivo, and the phosphorylation level
      is regulated by light and by [Ca(2+)], suggesting the importance of the
      modification in light adaptation.

PMID- 11292828
TI  - Proteolytic degradation and impaired secretion of an apolipoprotein A-I mutant
      associated with dominantly inherited hypoalphalipoproteinemia.
AB  - We have devised a combined in vivo, ex vivo, and in vitro approach to elucidate
      the mechanism(s) responsible for the hypoalphalipoproteinemia in heterozygous
      carriers of a naturally occurring apolipoprotein A-I (apoA-I) variant (Leu(159)
      to Arg) known as apoA-I Finland (apoA-I(FIN)). Adenovirus-mediated expression of
      apoA-I(FIN) decreased apoA-I and high density lipoprotein cholesterol
      concentrations in both wild-type C57BL/6J mice and in apoA-I-deficient mice
      expressing native human apoA-I (hapoA-I). Interestingly, apoA-I(FIN) was degraded
      in the plasma, and the extent of proteolysis correlated with the most significant
      reductions in murine apoA-I concentrations. ApoA-I(FIN) had impaired activation
      of lecithin:cholesterol acyltransferase in vitro compared with hapoA-I, but in a
      mixed lipoprotein preparation consisting of both hapoA-I and apoA-I(FIN) there
      was only a moderate reduction in the activation of this enzyme. Importantly,
      secretion of apoA-I was also decreased from primary apoA-I-deficient hepatocytes
      when hapoA-I was co-expressed with apoA-I(FIN) following infection with
      recombinant adenoviruses, a condition that mimics secretion in heterozygotes.
      Thus, this is the first demonstration of an apoA-I point mutation that decreases
      LCAT activation, impairs hepatocyte secretion of apoA-I, and makes apoA-I
      susceptible to proteolysis leading to dominantly inherited
      hypoalphalipoproteinemia.

PMID- 11292829
TI  - Molecular cloning and biological activity of a novel lysyl oxidase-related gene
      expressed in cartilage.
AB  - We cloned a cDNA encoding a novel lysyl oxidase-related protein, named LOXC, by
      suppression subtractive hybridization between differentiated and calcified ATDC5
      cells, a clonal mouse chondrogenic EC cell line. The deduced amino acid sequence
      of mouse LOXC consists of 757 amino acids and shows 50% identity with that of
      mouse lysyl oxidase. Northern blot analysis showed a distinct hybridization band
      of 5.4 kilobases, and Western blot analysis showed an immunoreactive band at 82
      kilodaltons. Expression of LOXC mRNA was detected in osteoblastic MC3T3-E1 cells
      and embryonic fibroblast C3H10T1/2 cells, whereas none of NIH3T3 fibroblasts and
      myoblastic C2C12 cells expressed LOXC mRNA in vitro. Moreover, the LOXC mRNA and
      protein levels dramatically increased throughout a process of chondrogenic
      differentiation in ATDC5 cells. In vivo, LOXC gene expression was localized in
      hypertrophic and calcified chondrocytes of growth plates in adult mice. The
      conditioned media of COS-7 cells transfected with the full-length LOXC cDNA
      showed the lysyl oxidase activity in both type I and type II collagens derived
      from chick embryos, and these activities of LOXC were inhibited by beta
      aminopropionitrile, a specific inhibitor of lysyl oxidase. Our data indicate that
      LOXC is expressed in cartilage in vivo and modulates the formation of a
      collagenous extracellular matrix.

PMID- 11292830
TI  - Functional equivalence of structurally distinct ribosomes in the malaria
      parasite, Plasmodium berghei.
AB  - Unlike most eukaryotes, many apicomplexan parasites contain only a few unlinked
      copies of ribosomal RNA (rRNA) genes. Based on stage-specific expression of these
      genes and structural differences among the rRNA molecules it has been suggested
      that Plasmodium spp. produce functionally different ribosomes in different
      developmental stages. This hypothesis was investigated through comparison of the
      structure of the large subunit rRNA molecules of the rodent malaria parasite,
      Plasmodium berghei, and by disruption of both of the rRNA gene units that are
      transcribed exclusively during development of this parasite in the mosquito (S
      type rRNA gene units). In contrast to the human parasite, Plasmodium falciparum,
      we did not find evidence of structural differences in core regions of the
      distinct large subunit rRNAs which are known to be associated with catalytic
      activity including the GTPase site that varies in P. falciparum. Knockout P.
      berghei parasites lacking either of the S-type gene units were able to complete
      development in both the vertebrate and mosquito hosts. These results formally
      exclude the hypothesis that two functionally different ribosome types distinct
      from the predominantly blood stage-expressed A-type ribosomes, are required for
      development of all Plasmodium species in the mosquito. The maintenance of two
      functionally equivalent rRNA genes might now be explained as a gene dosage
      phenomenon.

PMID- 11292831
TI  - A CalDAG-GEFI/Rap1/B-Raf cassette couples M(1) muscarinic acetylcholine receptors
      to the activation of ERK1/2.
AB  - In this study we examine signaling pathways linking the M(1) subtype of
      muscarinic acetylcholine receptor (M(1) mAChR) to activation of extracellular
      signal-regulated kinases (ERK) 1 and 2 in neuronal PC12D cells. We first show
      that activation of ERK1/2 by the M(1) mAChR agonist carbachol takes place
      primarily via a Ras-independent pathway that depends largely upon Rap1, another
      small GTP-binding protein in the Ras family. Rap1 in turn activates B-Raf, an
      upstream activator of ERK1/2. Consistent with these results, carbachol was found
      to activate Rap1 more potently than Ras. Similar to other small GTP-binding
      proteins, activation of Rap1 requires a guanine nucleotide exchange factor (GEF)
      to promote its conversion from the GDP- to GTP-bound form. Using specific
      antibodies, we show that a recently identified Rap1 GEF, calcium- and
      diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), is
      expressed in PC12D cells and that carbachol stimulates the formation of a complex
      containing CalDAG-GEFI, Rap1, and activated B-Raf. Finally, we show that
      expression of CalDAG-GEFI antisense RNA largely blocks carbachol-stimulated
      activation of hemagglutinin (HA)1-tagged B-Raf and formation of the CalDAG
      GEFI/Rap1/HA1-tagged B-Raf complex. Together, these data define a novel signaling
      pathway for M(1) mAChR, where increases in Ca(2+) and diacylglycerol stimulate
      the sequential activation of CalDAG-GEFI, Rap1, and B-Raf, resulting in the
      activation of MEK and ERK1/2.

PMID- 11292832
TI  - Tungstate Uptake by a highly specific ABC transporter in Eubacterium
      acidaminophilum.
AB  - The Gram-positive anaerobe Eubacterium acidaminophilum contains at least two
      tungsten-dependent enzymes: viologen-dependent formate dehydrogenase and aldehyde
      dehydrogenase. (185)W-Labeled tungstate was taken up by this organism with a
      maximum rate of 0.53 pmol min(-)1 mg(-)1 of protein at 36 degrees C. The uptake
      was not affected by equimolar amounts of molybdate. The genes tupABC coding for
      an ABC transporter specific for tungstate were cloned in the downstream region of
      genes encoding a tungsten-containing formate dehydrogenase. The substrate-binding
      protein, TupA, of this putative transporter was overexpressed in Escherichia
      coli, and its binding properties toward oxyanions were determined by a native
      polyacrylamide gel retardation assay. Only tungstate induced a shift of TupA
      mobility, suggesting that only this anion was specifically bound by TupA. If
      molybdate and sulfate were added in high molar excess (>1000-fold), they were
      also slightly bound by TupA. The K(d) value for tungstate was determined to be
      0.5 microm. The genes encoding the tungstate-specific ABC transporter exhibited
      highest similarities to putative transporters from Methanobacterium
      thermoautotrophicum, Haloferax volcanii, Vibrio cholerae, and Campylobacter
      jejuni. These five transporters represent a separate phylogenetic group of
      oxyanion ABC transporters as evident from analysis of the deduced amino acid
      sequences of the binding proteins. Downstream of the tupABC genes, the genes
      moeA, moeA-1, moaA, and a truncated moaC have been identified by sequence
      comparison of the deduced amino acid sequences. They should participate in the
      biosynthesis of the pterin cofactor that is present in molybdenum- and tungsten
      containing enzymes except nitrogenase.

PMID- 11292833
TI  - A cofactor of tRNA synthetase, p43, is secreted to up-regulate proinflammatory
      genes.
AB  - An auxiliary factor of mammalian multi-aminoacyl-tRNA synthetases, p43, is
      thought to be a precursor of endothelial monocyte-activating polypeptide II (EMAP
      II) that triggers proinflammation in leukocytes and macrophages. In the present
      work, however, we have shown that p43 itself is specifically secreted from intact
      mammalian cells, while EMAP II is released only when the cells are disrupted.
      Secretion of p43 was also observed when its expression was increased. These
      results suggest that p43 itself should be a real cytokine secreted by an active
      mechanism. To determine the cytokine activity and active domain of p43, we
      investigated tumor necrosis factor (TNF) and interleukin-8 (IL-8) production from
      human monocytic THP-1 cells treated with various p43 deletion mutants. The full
      length of p43 showed higher cytokine activity than EMAP II, further supporting
      p43 as the active cytokine. p43 was also shown to activate MAPKs and NFkappaB,
      and to induce cytokines and chemokines such as TNF, IL-8, MCP-1, MIP-1alpha, MIP
      1beta, MIP-2alpha, IL-1beta, and RANTES. Interestingly, the high level of p43 was
      observed in the foam cells of atherosclerotic lesions. Therefore, p43 could be a
      novel mediator of atherosclerosis development as well as other inflammation
      related diseases.

PMID- 11292834
TI  - Peroxisome proliferator-activated receptor gamma-mediated transcriptional up
      regulation of the hepatocyte growth factor gene promoter via a novel composite
      cis-acting element.
AB  - Hepatocyte growth factor (HGF) is a pleotropic polypeptide that can function as a
      morphogen, motogen, mitogen, angiogen, carcinogen, and tumor suppressor,
      depending on the target cell and tissue. Previous studies from our laboratory
      using transgenic mice have shown that HGF gene expression is tightly regulated at
      the transcriptional level and that the upstream regulatory elements are crucial
      for the control of HGF gene transcription. In the present study, we have
      identified and characterized one of these elements as a peroxisome proliferator
      activated receptor gamma (PPARgamma)-responsive element. This regulatory element
      was localized at -246 to -233 base pairs upstream from the transcription start
      site of the HGF gene promoter having the sequence GGGCCAGGTGACCT. Gel mobility
      shift and supershift assays demonstrated that this cis-acting element strongly
      binds to the PPARgamma isoforms as well as to chicken ovalbumin upstream promoter
      transcription factor, a member of the orphan nuclear receptor subfamily.
      Mutational analysis and gel mobility band shift assays indicated that the binding
      site is an inverted repeat of the AGGTCA motif with two spacers (inverted repeat
      2 configuration) and that the two spacers are important for PPARgamma binding.
      This binding site overlaps with functional binding sites for activating protein
      2, nuclear factor 1, and upstream stimulatory factor, and together, they
      constitute a multifunctional composite binding site through which these different
      transcription factors exert their regulatory effects on HGF promoter activity.
      Functional assays revealed that PPARgamma, with its ligand, 15-deoxy
      prostaglandin J2, strongly stimulates HGF promoter activity. On the other hand,
      nuclear factor 1, activating protein-2, and chicken ovalbumin upstream promoter
      transcription factor transcription factors repress the stimulatory action of
      PPARgamma by competing with PPARgamma for their overlapping binding sites.
      Furthermore, for the first time, our studies demonstrate that the PPARgamma
      ligand, 15-deoxy-prostaglandin J2, induces endogenous HGF mRNA and protein
      expression in fibroblasts in culture.

PMID- 11292835
TI  - Circular proteins in plants: solution structure of a novel macrocyclic trypsin
      inhibitor from Momordica cochinchinensis.
AB  - Much interest has been generated by recent reports on the discovery of circular
      (i.e. head-to-tail cyclized) proteins in plants. Here we report the three
      dimensional structure of one of the newest such circular proteins, MCoTI-II, a
      novel trypsin inhibitor from Momordica cochinchinensis, a member of the
      Cucurbitaceae plant family. The structure consists of a small beta-sheet, several
      turns, and a cystine knot arrangement of the three disulfide bonds.
      Interestingly, the molecular topology is similar to that of the plant cyclotides
      (Craik, D. J., Daly, N. L., Bond, T., and Waine, C. (1999) J. Mol. Biol. 294,
      1327-1336), which derive from the Rubiaceae and Violaceae plant families, have
      antimicrobial activities, and exemplify the cyclic cystine knot structural motif
      as part of their circular backbone. The sequence, biological activity, and plant
      family of MCoTI-II are all different from known cyclotides. However, given the
      structural similarity, cyclic backbone, and plant origin of MCoTI-II, we propose
      that MCoTI-II can be classified as a new member of the cyclotide class of
      proteins. The expansion of the cyclotides to include trypsin inhibitory activity
      and a new plant family highlights the importance and functional variability of
      circular proteins and the fact that they are more common than has previously been
      believed. Insights into the possible roles of backbone cyclization have been
      gained by a comparison of the structure of MCoTI-II with the homologous acyclic
      trypsin inhibitors CMTI-I and EETI-II from the Cucurbitaceae plant family.

PMID- 11292836
TI  - Activator protein-1 transcription factor mediates bombesin-stimulated
      cyclooxygenase-2 expression in intestinal epithelial cells.
AB  - Colorectal carcinogenesis is a complex, multistep process involving genetic
      alterations and progressive changes in signaling pathways regulating intestinal
      epithelial cell proliferation, differentiation, and apoptosis. Although
      cyclooxygenase-2 (COX-2), gastrin-releasing peptide (GRP), and its receptor, GRP
      R, are not normally expressed by the epithelial cells lining the human colon, the
      levels of all three proteins are aberrantly overexpressed in premalignant
      adenomatous polyps and colorectal carcinomas of humans. Overexpression of these
      proteins is associated with altered epithelial cell growth, adhesion, and tumor
      cell invasiveness, both in vitro and in vivo; however, a mechanistic link between
      GRP-R-mediated signaling pathways and increased COX-2 overexpression has not been
      established. We report that bombesin, a homolog of GRP, potently stimulates the
      expression of COX-2 mRNA and protein as well as the release of prostaglandin E(2)
      from a rat intestinal epithelial cell line engineered to express GRP-R. Bombesin
      stimulation of COX-2 expression requires an increase in [Ca(2+)](i), activation
      of extracellular signal-regulated kinase (ERK)-1 and -2 and p38(MAPK), and
      increased activation and expression of the transcription factors Elk-1, ATF-2, c
      Fos, and c-Jun. These data suggest that the expression of GRP-R in intestinal
      epithelial cells may play a role in carcinogenesis by stimulating COX-2
      overexpression through an activator protein-1-dependent pathway.

PMID- 11292837
TI  - Genetic evidence for the involvement of DNA ligase IV in the DNA-PK-dependent
      pathway of non-homologous end joining in mammalian cells.
AB  - Cells of vertebrates remove DNA double-strand breaks (DSBs) from their genome
      predominantly utilizing a fast, DNA-PKcs-dependent form of non-homologous end
      joining (D-NHEJ). Mutants with inactive DNA-PKcs remove the majority of DNA DSBs
      utilizing a slow, DNA-PKcs-independent pathway that does not utilize genes of the
      RAD52 epistasis group, is error-prone and can therefore be classified as a form
      of NHEJ (termed basic or B-NHEJ). We studied the role of DNA ligase IV in these
      pathways of NHEJ. Although biochemical studies show physical and functional
      interactions between the DNA-PKcs/Ku and the DNA ligase IV/Xrcc4 complexes
      suggesting operation within the same pathway, genetic evidence to support this
      notion is lacking in mammalian cells. Primary human fibroblasts (180BR) with an
      inactivating mutation in DNA ligase IV, rejoined DNA DSBs predominantly with slow
      kinetics similar to those observed in cells deficient in DNA-PKcs, or in wild
      type cells treated with wortmannin to inactivate DNA-PK. Treatment of 180BR cells
      with wortmannin had only a small effect on DNA DSB rejoining and no effect on
      cell radiosensitivity to killing although it sensitized control cells to 180BR
      levels. This is consistent with DNA ligase IV functioning as a component of the D
      NHEJ, and demonstrates the unperturbed operation of the DNA-PKcs-independent
      pathway (B-NHEJ) at significantly reduced levels of DNA ligase IV. In vitro,
      extracts of 180BR cells supported end joining of restriction endonuclease
      digested plasmid to the same degree as extracts of control cells when tested at
      10 mM Mg(2+). At 0.5 mM Mg(2+), where only DNA ligase IV is expected to retain
      activity, low levels of end joining ( approximately 10% of 10 mM) were seen in
      the control but there was no detectable activity in 180BR cells. Antibodies
      raised against DNA ligase IV did not measurably inhibit end joining at 10 mM
      Mg(2+) in either cell line. Thus, in contrast to the situation in vivo, end
      joining in vitro is dominated by pathways with properties similar to B-NHEJ that
      do not display a strong dependence on DNA ligase IV, with D-NHEJ retaining only a
      limited contribution. The implications of these observations to studies of NHEJ
      in vivo and in vitro are discussed.

PMID- 11292838
TI  - PEA3 sites within the progression elevated gene-3 (PEG-3) promoter and mitogen
      activated protein kinase contribute to differential PEG-3 expression in Ha-ras
      and v-raf oncogene transformed rat embryo cells.
AB  - Transformation of normal cloned rat embryo fibroblast (CREF) cells with cellular
      oncogenes results in acquisition of anchorage-independent growth and oncogenic
      potential in nude mice. These cellular changes correlate with an induction in the
      expression of a cancer progression-promoting gene, progression elevated gene-3
      (PEG-3). To define the mechanism of activation of PEG-3 as a function of
      transformation by the Ha-ras and v-raf oncogenes, evaluations of the signaling
      and transcriptional regulation of the approximately 2.0 kb promoter region of the
      PEG-3 gene, PEG-Prom, was undertaken. The full-length and various mutated regions
      of the PEG-Prom were linked to a luciferase reporter construct and tested for
      promoter activity in CREF and oncogene-transformed CREF cells. An analysis was
      also performed using CREF cells doubly transformed with Ha-ras and the Ha-ras
      specific suppressor gene Krev-1, which inhibits the transformed phenotype in
      vitro. These assays document an association between expression of the
      transcription regulator PEA3 and PEG-3. The levels of PEA3 and PEG-3 RNA and
      proteins are elevated in the oncogenically transformed CREF cells, and reduced in
      transformation and tumorigenic suppressed Ha-ras/Krev-1 doubly transformed CREF
      cells. Enhanced tumorigenic behavior, PEG-3 promoter function and PEG-3
      expression in Ha-ras transformed cells were all dependent upon increased activity
      within the mitogen-activated protein kinase (MAPK) pathway. Electrophoretic
      mobility shift assays and DNase I footprinting experiments indicate that PEA3
      binds to sites within the PEG-Prom in transformed rodent cells in an area
      adjacent to the TATA box in a MAPK-dependent fashion. These findings demonstrate
      an association between Ha-ras and v-raf transformation of CREF cells with
      elevated PEA3 and PEG-3 expression, and they implicate MAPK signaling via PEA3 as
      a signaling cascade involved in activation of the PEG-Prom.

PMID- 11292839
TI  - Development of an inducible pol III transcription system essentially requiring a
      mutated form of the TATA-binding protein.
AB  - We attempted to devise a transcription system in which a particular DNA sequence
      of interest could be inducibly expressed under the control of a modified
      polymerase III (pol III) promoter. Its activation requires a mutated
      transcription factor not contained endogenously in human cells. We constructed
      such a promoter by fusing elements of the beta-lactamase gene of Escherichia
      coli, containing a modified TATA-box and a pol III terminator, to the initiation
      region of the human U6 gene. This construct functionally resembles a 5'-regulated
      pol III gene and its transcribed segment can be exchanged for an arbitrary
      sequence. Its transcription in vitro by pol III requires the same factors as the
      U6 gene with the major exception that the modified TATA-box of this construct
      only interacts with a TATA-binding protein (TBP) mutant (TBP-DR2) but not with
      TBP wild-type (TBPwt). Its transcription therefore requires TBP-DR2 exclusively
      instead of TBPWT: In order to render the system inducible, we fused the gene
      coding for TBP-DR2 to a tetracycline control element and stably transfected this
      new construct into HeLa cells. Induction of such a stable and viable clone with
      tetracycline resulted in the expression of functional TBP-DR2. This system may
      conceptually be used in the future to inducibly express an arbitrary DNA sequence
      in vivo under the control of the above mentioned promoter.

PMID- 11292840
TI  - Inhibition of telomerase by 2'-O-(2-methoxyethyl) RNA oligomers: effect of
      length, phosphorothioate substitution and time inside cells.
AB  - 2'-O-(2-methoxyethyl) (2'-MOE) RNA possesses favorable pharmocokinetic properties
      that make it a promising option for the design of oligonucleotide drugs.
      Telomerase is a ribonucleoprotein that is up-regulated in many types of cancer,
      but its potential as a target for chemotherapy awaits the development of potent
      and selective inhibitors. Here we report inhibition of human telomerase by 2'-MOE
      RNA oligomers that are complementary to the RNA template region. Fully
      complementary oligomers inhibited telomerase in a cell extract with IC(50) values
      of 5-10 nM at 37 degrees C. IC(50) values for mismatch-containing oligomers
      varied with length and phosphorothioate substitution. After introduction into DU
      145 prostate cancer cells inhibition of telomerase activity persisted for up to 7
      days, equivalent to six population doublings. Inside cells discrimination between
      complementary and mismatch-containing oligomers increased over time. Our results
      reveal two oligomers as especially promising candidates for initiation of in vivo
      preclinical trials and emphasize that conclusions regarding oligonucleotide
      efficacy and specificity in cell extracts do not necessarily offer accurate
      predictions of activity inside cells.

PMID- 11292841
TI  - Heterogeneity in polyadenylation cleavage sites in mammalian mRNA sequences:
      implications for SAGE analysis.
AB  - The analysis of a human thyroid serial analysis of gene expression (SAGE) library
      shows the presence of an abundant SAGE tag corresponding to the mRNA of
      thyroglobulin (TG). Additional, less abundant tags are present that can not be
      linked to any other known gene, but show considerable homology to the wild-type
      TG tag. To determine whether these tags represent TG mRNA molecules with
      alternative cleavage, 3'-RACE clones were sequenced. The results show that the
      three putative TG SAGE tags can be attributed to TG transcripts and reflect the
      use of alternative polyadenylation cleavage sites downstream of a single
      polyadenylation signal in vivo. By screening more than 300 000 sequences
      corresponding to human, mouse and rat transcripts for this phenomenon we show
      that a considerable percentage of mRNA transcripts (44% human, 22% mouse and 22%
      rat) show cleavage site heterogeneity. When analyzing SAGE-generated expression
      data, this phenomenon should be considered, since, according to our calculations,
      2.8% of human transcripts show two or more different SAGE tags corresponding to a
      single gene because of alternative cleavage site selection. Both experimental and
      in silico data show that the selection of the specific cleavage site for poly(A)
      addition using a given polyadenylation signal is more variable than was
      previously thought.

PMID- 11292842
TI  - The interacting domains of three MutL heterodimers in man: hMLH1 interacts with
      36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2.
AB  - In human cells, hMLH1, hMLH3, hPMS1 and hPMS2 are four recognised and distinctive
      homologues of MutL, an essential component of the bacterial DNA mismatch repair
      (MMR) system. The hMLH1 protein forms three different heterodimers with one of
      the other MutL homologues. As a first step towards functional analysis of these
      molecules, we determined the interacting domains of each heterodimer and tried to
      understand their common features. Using a yeast two-hybrid assay, we show that
      these MutL homologues can form heterodimers by interacting with the same amino
      acid residues of hMLH1, residues 492-742. In contrast, three hMLH1 partners,
      hMLH3, hPMS1 and hPMS2 contain the 36 homologous amino acid residues that
      interact strongly with hMLH1. Contrary to the previous studies, these homologous
      residues reside at the N-terminal regions of three subdomains conserved in MutL
      homologues in many species. Interestingly, these residues in hPMS2 and hMLH3 may
      form coiled-coil structures as predicted by the MULTICOIL program. Furthermore,
      we show that there is competition for the interacting domain in hMLH1 among the
      three other MutL homologues. Therefore, the quantitative balance of these three
      MutL heterodimers may be important in their functions.

PMID- 11292843
TI  - Treble clef finger--a functionally diverse zinc-binding structural motif.
AB  - Detection of similarity is particularly difficult for small proteins and thus
      connections between many of them remain unnoticed. Structure and sequence
      analysis of several metal-binding proteins reveals unexpected similarities in
      structural domains classified as different protein folds in SCOP and suggests
      unification of seven folds that belong to two protein classes. The common motif,
      termed treble clef finger in this study, forms the protein structural core and is
      25-45 residues long. The treble clef motif is assembled around the central zinc
      ion and consists of a zinc knuckle, loop, beta-hairpin and an alpha-helix. The
      knuckle and the first turn of the helix each incorporate two zinc ligands. Treble
      clef domains constitute the core of many structures such as ribosomal proteins
      L24E and S14, RING fingers, protein kinase cysteine-rich domains, nuclear
      receptor-like fingers, LIM domains, phosphatidylinositol-3-phosphate-binding
      domains and His-Me finger endonucleases. The treble clef finger is a uniquely
      versatile motif adaptable for various functions. This small domain with a 25
      residue structural core can accommodate eight different metal-binding sites and
      can have many types of functions from binding of nucleic acids, proteins and
      small molecules, to catalysis of phosphodiester bond hydrolysis. Treble clef
      motifs are frequently incorporated in larger structures or occur in doublets.
      Present analysis suggests that the treble clef motif defines a distinct
      structural fold found in proteins with diverse functional properties and forms
      one of the major zinc finger groups.

PMID- 11292844
TI  - The wing in yeast heat shock transcription factor (HSF) DNA-binding domain is
      required for full activity.
AB  - The yeast heat shock transcription factor (HSF) belongs to the winged helix
      family of proteins. HSF binds DNA as a trimer, and additional trimers can bind
      DNA co-operatively. Unlike other winged helix-turn-helix proteins, HSF's wing
      does not appear to contact DNA, as based on a previously solved crystal
      structure. Instead, the structure implies that the wing is involved in protein
      protein interactions, possibly within a trimer or between adjacent trimers. To
      understand the function of the wing in the HSF DNA-binding domain, a
      Saccharomyces cerevisiae strain was created that expresses a wingless HSF
      protein. This strain grows normally at 30 degrees C, but shows a decrease in
      reporter gene expression during constitutive and heat-shocked conditions. Removal
      of the wing does not affect the stability or trimeric nature of a protein
      fragment containing the DNA-binding and trimerization domains. Removal of the
      wing does result in a decrease in DNA-binding affinity. This defect was mainly
      observed in the ability to form the first trimer-bound complex, as the formation
      of larger complexes is unaffected by the deletion. Our results suggest that the
      wing is not involved in the highly co-operative nature of HSF binding, but may be
      important in stabilizing the first trimer bound to DNA.

PMID- 11292845
TI  - Gain- and loss-of-function of Rhp51, a Rad51 homolog in fission yeast, reveals
      dissimilarities in chromosome integrity.
AB  - Rad51 is crucial not only in homologous recombination and recombinational repair
      but also in normal cellular growth. To address the role of Rad51 in normal cell
      growth we investigated morphological changes of cells after overexpression of
      wild-type and a dominant negative form of Rad51 in fission yeast. Rhp51, a Rad51
      homolog in Schizosaccharomyces pombe, has a highly conserved ATP-binding motif.
      Rhp51 K155A, which has a single substitution in this motif, failed to rescue
      hypersensitivity of a rhp51 mutant to methyl methanesulfonate (MMS) and UV,
      whereas it binds normally to Rhp51 and Rad22, a Rad52 homolog. Two distinct
      cellular phenotypes were observed when Rhp51 or Rhp51 K155A was overexpressed in
      normal cells. Overexpression of Rhp51 caused lethality in the absence of DNA
      damaging agents, with acquisition of a cell cycle mutant phenotype and
      accumulation of a 1C DNA population. On the other hand, overexpression of Rhp51
      K155A led to a delay in G(2) with decondensed nuclei, which resembled the
      phenotype of rhp51. The latter also exhibited MMS and UV sensitivity, indicating
      that Rhp51 K155A has a dominant negative effect. These results suggest an
      association between DNA replication and Rad51 function.

PMID- 11292846
TI  - A novel human hexameric DNA helicase: expression, purification and
      characterization.
AB  - We have cloned, expressed and purified a hexameric human DNA helicase (hHcsA)
      from HeLa cells. Sequence analysis demonstrated that the hHcsA has strong
      sequence homology with DNA helicase genes from Saccharomyces cerevisiae and
      Caenorhabditis elegans, indicating that this gene appears to be well conserved
      from yeast to human. The hHcsA gene was cloned and expressed in Escherichia coli
      and purified to homogeneity. The expressed protein had a subunit molecular mass
      of 116 kDa and analysis of its native molecular mass by size exclusion
      chromatography suggested that hHcsA is a hexameric protein. The hHcsA protein had
      a strong DNA-dependent ATPase activity that was stimulated >/=5-fold by single
      stranded DNA (ssDNA). Human hHcsA unwinds duplex DNA and analysis of the polarity
      of translocation demonstrated that the polarity of DNA unwinding was in a 5'-->3'
      direction. The helicase activity was stimulated by human and yeast replication
      protein A, but not significantly by E.coli ssDNA-binding protein. We have
      analyzed expression levels of the hHcsA gene in HeLa cells during various phases
      of the cell cycle using in situ hybridization analysis. Our results indicated
      that the expression of the hHcsA gene, as evidenced from the mRNA levels, is cell
      cycle-dependent. The maximal level of hHcsA expression was observed in late
      G(1)/early S phase, suggesting a possible role for this protein during S phase
      and in DNA synthesis.

PMID- 11292847
TI  - Sequences upstream of the branch site are required to form helix II between U2
      and U6 snRNA in a trans-splicing reaction.
AB  - Three different base paired stems form between U2 and U6 snRNA over the course of
      the mRNA splicing reaction (helices I, II and III). One possible function of
      U2/U6 helix II is to facilitate subsequent U2/U6 helix I and III interactions,
      which participate directly in catalysis. Using an in vitro trans-splicing assay,
      we investigated the function of sequences located just upstream from the branch
      site (BS). We find that these upstream sequences are essential for stable binding
      of U2 to the branch region, and for U2/U6 helix II formation, but not for initial
      U2/BS pairing. We also show that non-functional upstream sequences cause U2 snRNA
      stem-loop IIa to be exposed to dimethylsulfate modification, perhaps reflecting a
      U2 snRNA conformational change and/or loss of SF3b proteins. Our data suggest
      that initial binding of U2 snRNP to the BS region must be stabilized by an
      interaction with upstream sequences before U2/U6 helix II can form or U2 stem
      loop IIa can participate in spliceosome assembly.

PMID- 11292848
TI  - PartsList: a web-based system for dynamically ranking protein folds based on
      disparate attributes, including whole-genome expression and interaction
      information.
AB  - As the number of protein folds is quite limited, a mode of analysis that will be
      increasingly common in the future, especially with the advent of structural
      genomics, is to survey and re-survey the finite parts list of folds from an
      expanding number of perspectives. We have developed a new resource, called
      PartsList, that lets one dynamically perform these comparative fold surveys. It
      is available on the web at http://bioinfo.mbb.yale.edu/partslist and
      http://www.partslist.org. The system is based on the existing fold
      classifications and functions as a form of companion annotation for them,
      providing 'global views' of many already completed fold surveys. The central idea
      in the system is that of comparison through ranking; PartsList will rank the
      approximately 420 folds based on more than 180 attributes. These include: (i)
      occurrence in a number of completely sequenced genomes (e.g. it will show the
      most common folds in the worm versus yeast); (ii) occurrence in the structure
      databank (e.g. most common folds in the PDB); (iii) both absolute and relative
      gene expression information (e.g. most changing folds in expression over the cell
      cycle); (iv) protein-protein interactions, based on experimental data in yeast
      and comprehensive PDB surveys (e.g. most interacting fold); (v) sensitivity to
      inserted transposons; (vi) the number of functions associated with the fold (e.g.
      most multi-functional folds); (vii) amino acid composition (e.g. most Cys-rich
      folds); (viii) protein motions (e.g. most mobile folds); and (ix) the level of
      similarity based on a comprehensive set of structural alignments (e.g. most
      structurally variable folds). The integration of whole-genome expression and
      protein-protein interaction data with structural information is a particularly
      novel feature of our system. We provide three ways of visualizing the rankings: a
      profiler emphasizing the progression of high and low ranks across many pre
      selected attributes, a dynamic comparer for custom comparisons and a numerical
      rankings correlator. These allow one to directly compare very different
      attributes of a fold (e.g. expression level, genome occurrence and maximum
      motion) in the uniform numerical format of ranks. This uniform framework, in
      turn, highlights the way that the frequency of many of the attributes falls off
      with approximate power-law behavior (i.e. according to V(-b), for attribute value
      V and constant exponent b), with a few folds having large values and most having
      small values.

PMID- 11292849
TI  - Substrate-specific inhibition of RecQ helicase.
AB  - The RecQ helicases constitute a small but highly conserved helicase family.
      Proteins in this family are of particular interest because they are critical to
      maintenance of genomic stability in prokaryotes and eukaryotes. Eukaryotic RecQ
      helicase family members have been shown to unwind not only DNA duplexes but also
      DNAs with alternative structures, including structures stabilized by G quartets
      (G4 DNAs). We report that Escherichia coli RecQ can also unwind G4 DNAs, and that
      unwinding requires ATP and divalent cation. RecQ helicase is comparably active on
      duplex and G4 DNA substrates, as measured by direct comparison of protein
      activity and by competition assays. The porphyrin derivative, N-methyl
      mesoporphyrin IX (NMM), is a highly specific inhibitor of RecQ unwinding activity
      on G4 DNA but not duplex DNA: the inhibition constant (K(i)) for NMM inhibition
      of G4 DNA unwinding is 1.7 microM, approximately two orders of magnitude below
      the K(i) for inhibition of duplex DNA unwinding (>100 microM). NMM may therefore
      prove to be a valuable compound for substrate-specific inhibition of other RecQ
      family helicases in vitro and in vivo.

PMID- 11292850
TI  - Identification of the yeast cytidine deaminase CDD1 as an orphan C-->U RNA
      editase.
AB  - Yeast co-expressing rat APOBEC-1 and a fragment of human apolipoprotein B (apoB)
      mRNA assembled functional editosomes and deaminated C6666 to U in a mooring
      sequence-dependent fashion. The occurrence of APOBEC-1-complementing proteins
      suggested a naturally occurring mRNA editing mechanism in yeast. Previously, a
      hidden Markov model identified seven yeast genes encoding proteins possessing
      putative zinc-dependent deaminase motifs. Here, only CDD1, a cytidine deaminase,
      is shown to have the capacity to carry out C-->U editing on a reporter mRNA. This
      is only the second report of a cytidine deaminase that can use mRNA as a
      substrate. CDD1-dependent editing was growth phase regulated and demonstrated
      mooring sequence-dependent editing activity. Candidate yeast mRNA substrates were
      identified based on their homology with the mooring sequence-containing
      tripartite motif at the editing site of apoB mRNA and their ability to be edited
      by ectopically expressed APOBEC-1. Naturally occurring yeast mRNAs edited to a
      significant extent by CDD1 were, however, not detected. We propose that CDD1 be
      designated an orphan C-->U editase until its native RNA substrate, if any, can be
      identified and that it be added to the CDAR (cytidine deaminase acting on RNA)
      family of editing enzymes.

PMID- 11292851
TI  - Highly efficient base excision repair (BER) in human and rat male germ cells.
AB  - The quality of germ cell DNA is critical for the fate of the offspring, yet there
      is limited knowledge of the DNA repair capabilities of such cells. One of the
      main DNA repair pathways is base excision repair (BER) which is initiated by DNA
      glycosylases that excise damaged bases, followed by incision of the generated
      abasic (AP) sites. We have studied human and rat methylpurine-DNA glycosylase
      (MPG), uracil-DNA glycosylase (UNG), and the major AP endonuclease (HAP1/APEX) in
      male germ cells. Enzymatic activities and western analyses indicate that these
      enzymes are present in human and rat male germ cells in amounts that are at least
      as high as in somatic cells. Minor differences were observed between different
      cellular stages of rat spermatogenesis and spermiogenesis. Repair of methylated
      DNA was also studied at the cellular level using the Comet assay. The repair was
      highly efficient in both human and rat male germ cells, in primary spermatocytes
      as well as round spermatids, compared to rat mononuclear blood cells or
      hepatocytes. This efficient BER removes frequently occurring DNA lesions that
      arise spontaneously or via environmental agents, thereby minimising the number of
      potential mutations transferred to the next generation.

PMID- 11292852
TI  - Nucleotide excision repair in rat male germ cells: low level of repair in intact
      cells contrasts with high dual incision activity in vitro.
AB  - The acquisition of genotoxin-induced mutations in the mammalian germline is
      detrimental to the stable transfer of genomic information. In somatic cells,
      nucleotide excision repair (NER) is a major pathway to counteract the mutagenic
      effects of DNA damage. Two NER subpathways have been identified, global genome
      repair (GGR) and transcription-coupled repair (TCR). In contrast to somatic
      cells, little is known regarding the expression of these pathways in germ cells.
      To address this basic question, we have studied NER in rat spermatogenic cells in
      crude cell suspension, in enriched cell stages and within seminiferous tubules
      after exposure to UV or N-acetoxy-2-acetylaminofluorene. Surprisingly, repair in
      spermatogenic cells was inefficient in the genome overall and in
      transcriptionally active genes indicating non-functional GGR and TCR. In
      contrast, extracts from early/mid pachytene cells displayed dual incision
      activity in vitro as high as extracts from somatic cells, demonstrating that the
      proteins involved in incision are present and functional in premeiotic cells.
      However, incision activities of extracts from diplotene cells and round
      spermatids were low, indicating a stage-dependent expression of incision
      activity. We hypothesize that sequestering of NER proteins by mispaired regions
      in DNA involved in synapsis and recombination may underlie the lack of NER
      activity in premeiotic cells.

PMID- 11292853
TI  - Detection and determination of oligonucleotide triplex formation-mediated
      transcription-coupled DNA repair in HeLa nuclear extracts.
AB  - Transcription-coupled repair (TCR) plays an important role in removing DNA damage
      from actively transcribed genes. It has been speculated that TCR is the most
      important mechanism for repairing DNA damage in non-dividing cells such as
      neurons. Therefore, abnormal TCR may contribute to the development of many age
      related and neurodegenerative diseases. However, the molecular mechanism of TCR
      is not well understood. Oligonucleotide DNA triplex formation provides an ideal
      system to dissect the molecular mechanism of TCR since triplexes can be formed in
      a sequence-specific manner to inhibit transcription of target genes. We have
      recently studied the molecular mechanism of triplex-forming oligonucleotide (TFO)
      mediated TCR in HeLa nuclear extracts. Using plasmid constructs we demonstrate
      that the level of TFO-mediated DNA repair activity is directly correlated with
      the level of transcription of the plasmid in HeLa nuclear extracts. TFO-mediated
      DNA repair activity was further linked with transcription since the presence of
      rNTPs in the reaction was essential for AG30-mediated DNA repair activity in HeLa
      nuclear extracts. The involvement of individual components, including TFIID,
      TFIIH, RNA polymerase II and xeroderma pigmentosum group A (XPA), in the triplex
      mediated TCR process was demonstrated in HeLa nuclear extracts using
      immunodepletion assays. Importantly, our studies also demonstrated that XPC, a
      component involved in global genome DNA repair, is involved in the AG30-mediated
      DNA repair process. The results obtained in this study provide an important new
      understanding of the molecular mechanisms involved in the TCR process in
      mammalian cells.

PMID- 11292854
TI  - E2F-dependent transcription of the raf proto-oncogene during Drosophila
      development.
AB  - D-raf, a Drosophila homolog of the raf proto-oncogene, has diverse functions
      throughout development and is transcribed in a wide range of tissues, with high
      levels of expression in the ovary and in association with rapid proliferation.
      The expression pattern resembles those of S phase genes, which are regulated by
      E2F transcription factors. In the 5'-flanking region of D-raf, four sequences
      (E2F sites 1-4) similar to the E2F recognition sequence were found, one of them
      (E2F site 3) being recognized efficiently by Drosophila E2F (dE2F) in vitro.
      Transient luciferase expression assays confirmed activation of the D-raf gene
      promoter by dE2F/dDP. Expression of Draf-lacZ was greatly reduced in embryos
      homozygous for the dE2F mutation. These results suggest that dE2F is likely to be
      an important regulator of D-raf transcription.

PMID- 11292855
TI  - An evaluation of the performance of cDNA microarrays for detecting changes in
      global mRNA expression.
AB  - The cDNA microarray is one technological approach that has the potential to
      accurately measure changes in global mRNA expression levels. We report an
      assessment of an optimized cDNA microarray platform to generate accurate, precise
      and reliable data consistent with the objective of using microarrays as an
      acquisition platform to populate gene expression databases. The study design
      consisted of two independent evaluations with 70 arrays from two different
      manufactured lots and used three human tissue sources as samples: placenta, brain
      and heart. Overall signal response was linear over three orders of magnitude and
      the sensitivity for any element was estimated to be 2 pg mRNA. The calculated
      coefficient of variation for differential expression for all non-differentiated
      elements was 12-14% across the entire signal range and did not vary with array
      batch or tissue source. The minimum detectable fold change for differential
      expression was 1.4. Accuracy, in terms of bias (observed minus expected
      differential expression ratio), was less than 1 part in 10 000 for all non
      differentiated elements. The results presented in this report demonstrate the
      reproducible performance of the cDNA microarray technology platform and the
      methods provide a useful framework for evaluating other technologies that monitor
      changes in global mRNA expression.

PMID- 11292856
TI  - Optimizing the detection of nascent transcripts by RNA fluorescence in situ
      hybridization.
AB  - An unusual feature of the mammalian genome is the number of genes exhibiting
      monoallelic expression. Recently random monoallelic expression of autosomal genes
      has been reported for olfactory and Ly-49 NK receptor genes, as well as for Il-2,
      Il-4 and Pax5. RNA fluorescence in situ hybridization (FISH) has been exploited
      to monitor allelic expression by visualizing the number of sites of transcription
      in individual nuclei. However, the sensitivity of this technique is difficult to
      determine for a given gene. We show that by combining DNA and RNA FISH it is
      possible to control for the hybridization efficiency and the accessibility and
      visibility of fluorescent probes within the nucleus.

PMID- 11292857
TI  - Sequence-tagged microsatellite profiling (STMP): a rapid technique for developing
      SSR markers.
AB  - We describe a technique, sequence-tagged microsatellite profiling (STMP), to
      rapidly generate large numbers of simple sequence repeat (SSR) markers from
      genomic or cDNA. This technique eliminates the need for library screening to
      identify SSR-containing clones and provides an approximately 25-fold increase in
      sequencing throughput compared to traditional methods. STMP generates short but
      characteristic nucleotide sequence tags for fragments that are present within a
      pool of SSR amplicons. These tags are then ligated together to form concatemers
      for cloning and sequencing. The analysis of thousands of tags gives rise to a
      representational profile of the abundance and frequency of SSRs within the DNA
      pool, from which low copy sequences can be identified. As each tag contains
      sufficient nucleotide sequence for primer design, their conversion into PCR
      primers allows the amplification of corresponding full-length fragments from the
      pool of SSR amplicons. These fragments permit the full characterisation of a SSR
      locus and provide flanking sequence for the development of a microsatellite
      marker. Alternatively, sequence tag primers can be used to directly amplify
      corresponding SSR loci from genomic DNA, thereby reducing the cost of developing
      a microsatellite marker to the synthesis of just one sequence-specific primer. We
      demonstrate the utility of STMP by the development of SSR markers in bread wheat.

PMID- 11292858
TI  - Targeted development of informative microsatellite (SSR) markers.
AB  - We describe a novel approach, selectively amplified microsatellite (SAM)
      analysis, for the targeted development of informative simple sequence repeat
      (SSR) markers. A modified selectively amplified microsatellite polymorphic loci
      assay is used to generate multi-locus SSR fingerprints that provide a source of
      polymorphic DNA markers (SAMs) for use in genetic studies. These polymorphisms
      capture the repeat length variation associated with SSRs and allow their
      chromosomal location to be determined prior to the expense of isolating and
      characterising individual loci. SAMs can then be converted to locus-specific SSR
      markers with the design and synthesis of a single primer specific to the
      conserved region flanking the repeat. This approach offers a cost-efficient and
      rapid method for developing SSR markers for predetermined chromosomal locations
      and of potential informativeness. The high recovery rate of useful SSR markers
      makes this strategy a valuable tool for population and genetic mapping studies.
      The utility of SAM analysis was demonstrated by the development of SSR markers in
      bread wheat.

PMID- 11292859
TI  - Single crystals of single-walled carbon nanotubes formed by self-assembly.
AB  - We report the self-assembly of single crystals of single-walled carbon nanotubes
      (SWCNTs) using thermolysis of nano-patterned precursors. The synthesis of these
      perfectly ordered, single crystals of SWCNTs results in extended structures with
      dimension on the micrometer scale. Each crystal is composed of an ordered array
      of tubes with identical diameters and chirality, although these properties vary
      between crystals. The results show that SWCNTs can be produced as a perfect bulk
      material on the micrometer scale and point toward the synthesis of bulk
      macroscopic crystalline material.

PMID- 11292860
TI  - Regulation of longevity and stress resistance by Sch9 in yeast.
AB  - The protein kinase Akt/protein kinase B (PKB) is implicated in insulin signaling
      in mammals and functions in a pathway that regulates longevity and stress
      resistance in Caenorhabditis elegans. We screened for long-lived mutants in
      nondividing yeast Saccharomyces cerevisiae and identified mutations in adenylate
      cyclase and SCH9, which is homologous to Akt/PKB, that increase resistance to
      oxidants and extend life-span by up to threefold. Stress-resistance transcription
      factors Msn2/Msn4 and protein kinase Rim15 were required for this life-span
      extension. These results indicate that longevity is associated with increased
      investment in maintenance and show that highly conserved genes play similar roles
      in life-span regulation in S. cerevisiae and higher eukaryotes.

PMID- 11292861
TI  - Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2
      regulated prolyl hydroxylation.
AB  - Hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central
      role in the regulation of gene expression by oxygen. In oxygenated and iron
      replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that
      involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3
      ligase complex. This process is suppressed by hypoxia and iron chelation,
      allowing transcriptional activation. Here we show that the interaction between
      human pVHL and a specific domain of the HIF-1alpha subunit is regulated through
      hydroxylation of a proline residue (HIF-1alpha P564) by an enzyme we have termed
      HIF-alpha prolyl-hydroxylase (HIF-PH). An absolute requirement for dioxygen as a
      cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a
      cellular oxygen sensor.

PMID- 11292862
TI  - HIFalpha targeted for VHL-mediated destruction by proline hydroxylation:
      implications for O2 sensing.
AB  - HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal
      role in cellular adaptation to changes in oxygen availability. In the presence of
      oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the
      von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds
      to a short HIF-derived peptide when a conserved proline residue at the core of
      this peptide is hydroxylated. Because proline hydroxylation requires molecular
      oxygen and Fe(2+), this protein modification may play a key role in mammalian
      oxygen sensing.

PMID- 11292863
TI  - Signal transduction. How do cells sense oxygen?
AB  - How do organisms sense the amount of oxygen in the environment and respond
      appropriately when the amount of oxygen decreases (a condition called hypoxia)?
      In their Perspective, Zhu and Bunn discuss new findings (Ivan et al., Jaakkola et
      al.) that reveal how the HIF transcription factor, which switches on a group of
      hypoxia-response proteins, is itself regulated by changes in oxygen tension. The
      authors are in the Hematology Division of the Department of Medicine, Brigham and
      Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. E-mail:
      zhu@calvin.bwh.harvard.edu, bunn@calvin.bwh.harvard.edu

PMID- 11292864
TI  - HIV-1 RNA editing, hypermutation, and error-prone reverse transcription.

PMID- 11292865
TI  - Experimental verification of a negative index of refraction.
AB  - We present experimental scattering data at microwave frequencies on a structured
      metamaterial that exhibits a frequency band where the effective index of
      refraction (n) is negative. The material consists of a two-dimensional array of
      repeated unit cells of copper strips and split ring resonators on interlocking
      strips of standard circuit board material. By measuring the scattering angle of
      the transmitted beam through a prism fabricated from this material, we determine
      the effective n, appropriate to Snell's law. These experiments directly confirm
      the predictions of Maxwell's equations that n is given by the negative square
      root of epsilon.mu for the frequencies where both the permittivity (epsilon) and
      the permeability (mu) are negative. Configurations of geometrical optical designs
      are now possible that could not be realized by positive index materials.

PMID- 11292866
TI  - Three-dimensionally ordered array of air bubbles in a polymer film.
AB  - We report the formation of a three-dimensionally ordered array of air bubbles of
      monodisperse pore size in a polymer film through a templating mechanism based on
      thermocapillary convection. Dilute solutions of a simple, coil-like polymer in a
      volatile solvent are cast on a glass slide in the presence of moist air flowing
      across the surface. Evaporative cooling and the generation of an ordered array of
      breath figures leads to the formation of multilayers of hexagonally packed water
      droplets that are preserved in the final, solid polymer film as spherical air
      bubbles. The dimensions of these bubbles can be controlled simply by changing the
      velocity of the airflow across the surface. When these three-dimensionally
      ordered macroporous materials have pore dimensions comparable to the wavelength
      of visible light, they are of interest as photonic band gaps and optical stop
      bands.

PMID- 11292867
TI  - Carbon dioxide degassing by advective flow from Usu volcano, Japan.
AB  - Magmatic carbon dioxide (CO2) degassing has been documented before the 31 March
      2000 eruption of Usu volcano, Hokkaido, Japan. Six months before the eruption, an
      increase in CO2 flux was detected on the summit caldera, from 120 (September
      1998) to 340 metric tons per day (September 1999), followed by a sudden decrease
      to 39 metric tons per day in June 2000, 3 months after the eruption. The change
      in CO2 flux and seismic observations suggests that before the eruption, advective
      processes controlled gas migration toward the surface. The decrease in flux after
      the eruption at the summit caldera could be due to a rapid release of CO2 during
      the eruption from ascending dacitic dikes spreading away from the magma chamber
      beneath the caldera.

PMID- 11292869
TI  - Tropical origins for recent North Atlantic climate change.
AB  - Evidence is presented that North Atlantic climate change since 1950 is linked to
      a progressive warming of tropical sea surface temperatures, especially over the
      Indian and Pacific Oceans. The ocean changes alter the pattern and magnitude of
      tropical rainfall and atmospheric heating, the atmospheric response to which
      includes the spatial structure of the North Atlantic Oscillation (NAO). The slow,
      tropical ocean warming has thus forced a commensurate trend toward one extreme
      phase of the NAO during the past half-century.

PMID- 11292868
TI  - Control of nitrogen export from watersheds by headwater streams.
AB  - A comparative (15)N-tracer study of nitrogen dynamics in headwater streams from
      biomes throughout North America demonstrates that streams exert control over
      nutrient exports to rivers, lakes, and estuaries. The most rapid uptake and
      transformation of inorganic nitrogen occurred in the smallest streams. Ammonium
      entering these streams was removed from the water within a few tens to hundreds
      of meters. Nitrate was also removed from stream water but traveled a distance 5
      to 10 times as long, on average, as ammonium. Despite low ammonium concentration
      in stream water, nitrification rates were high, indicating that small streams are
      potentially important sources of atmospheric nitrous oxide. During seasons of
      high biological activity, the reaches of headwater streams typically export
      downstream less than half of the input of dissolved inorganic nitrogen from their
      watersheds.

PMID- 11292870
TI  - Amphibians as indicators of early tertiary "out-of-India" dispersal of
      vertebrates.
AB  - Sixty-five million years ago, massive volcanism produced on the India-Seychelles
      landmass the largest continental lava deposit (Deccan Traps) of the past 200
      million years. Using a molecular clock-independent approach for inferring dating
      information from molecular phylogenies, we show that multiple lineages of frogs
      survived Deccan Traps volcanism after millions of years of isolation on drifting
      India. The collision between the Indian and Eurasian plates was followed by wide
      dispersal of several of these lineages. This "out-of-India" scenario reveals a
      zoogeographical pattern that might reconcile paleontological and molecular data
      in other vertebrate groups.

PMID- 11292871
TI  - Rising CO2 levels and the fecundity of forest trees.
AB  - We determined the reproductive response of 19-year-old loblolly pine (Pinus
      taeda) to 4 years of carbon dioxide (CO2) enrichment (ambient concentration plus
      200 microliters per liter) in an intact forest. After 3 years of CO2 fumigation,
      trees were twice as likely to be reproductively mature and produced three times
      as many cones and seeds as trees at ambient CO2 concentration. A disproportionate
      carbon allocation to reproduction under CO2 enrichment results in trees reaching
      maturity sooner and at a smaller size. This reproductive response to future
      increases in atmospheric CO2 concentration is expected to change loblolly
      dispersal and recruitment patterns.

PMID- 11292872
TI  - Ecological degradation in protected areas: the case of Wolong Nature Reserve for
      giant pandas.
AB  - It is generally perceived that biodiversity is better protected from human
      activities after an area is designated as a protected area. However, we found
      that this common perception was not true in Wolong Nature Reserve (southwestern
      China), which was established in 1975 as a "flagship" protected area for the
      world-renowned endangered giant pandas. Analyses of remote sensing data from pre-
      and post-establishment periods indicate that the reserve has become more
      fragmented and less suitable for giant panda habitation. The rate of loss of high
      quality habitat after the reserve's establishment was much higher than before the
      reserve was created, and the fragmentation of high-quality habitat became far
      more severe. After the creation of the reserve, rates of habitat loss and
      fragmentation inside the reserve unexpectedly increased to levels that were
      similar to or higher than those outside the reserve, in contrast to the situation
      before the reserve was created.

PMID- 11292873
TI  - Delayed compensation for missing keystone species by colonization.
AB  - Because individual species can play key roles, the loss of species through
      extinction or their gain through colonization can cause major changes in
      ecosystems. For almost 20 years after kangaroo rats were experimentally removed
      from a Chihuahuan desert ecosystem in the United States, other rodent species
      were unable to compensate and use the available resources. This changed abruptly
      in 1995, when an alien species of pocket mouse colonized the ecosystem, used most
      of the available resources, and compensated almost completely for the missing
      kangaroo rats. These results demonstrate the importance of individual species and
      of colonization and extinction events in the structure and dynamics of
      ecosystems.

PMID- 11292874
TI  - Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate
      protein.
AB  - The Drosophila melanogaster gene chico encodes an insulin receptor substrate that
      functions in an insulin/insulin-like growth factor (IGF) signaling pathway. In
      the nematode Caenorhabditis elegans, insulin/IGF signaling regulates adult
      longevity. We found that mutation of chico extends fruit fly median life-span by
      up to 48% in homozygotes and 36% in heterozygotes. Extension of life-span was not
      a result of impaired oogenesis in chico females, nor was it consistently
      correlated with increased stress resistance. The dwarf phenotype of chico
      homozygotes was also unnecessary for extension of life-span. The role of
      insulin/IGF signaling in regulating animal aging is therefore evolutionarily
      conserved.

PMID- 11292875
TI  - A mutant Drosophila insulin receptor homolog that extends life-span and impairs
      neuroendocrine function.
AB  - The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to
      mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal
      transducer regulating worm dauer formation and adult longevity. We describe a
      heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females
      with up to an 85% extension of adult longevity and dwarf males with reduced late
      age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile
      hormone analog restores life expectancy toward that of wild-type controls. We
      conclude that juvenile hormone deficiency, which results from InR signal pathway
      mutation, is sufficient to extend life-span, and that in flies, insulin-like
      ligands nonautonomously mediate aging through retardation of growth or activation
      of specific endocrine tissue.

PMID- 11292876
TI  - A link between virulence and ecological abundance in natural populations of
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a major cause of severe infection in humans and yet is
      carried without symptoms by a large proportion of the population. We used
      multilocus sequence typing to characterize isolates of S. aureus recovered from
      asymptomatic nasal carriage and from episodes of severe disease within a defined
      population. We identified a number of frequently carried genotypes that were
      disproportionately common as causes of disease, even taking into account their
      relative abundance among carriage isolates. The existence of these ecologically
      abundant hypervirulent clones suggests that factors promoting the ecological
      fitness of this important pathogen also increase its virulence.

PMID- 11292877
TI  - Antimicrobial resistance in the ICU: The time for action is now.

PMID- 11292878
TI  - Increasing prevalence of antimicrobial resistance in intensive care units.
AB  - The unique nature of the intensive care unit (ICU) environment makes this part of
      the hospital a focus for the emergence and spread of many antimicrobial-resistant
      pathogens. There are ample opportunities for the cross-transmission of resistant
      bacteria from patient to patient, and patients are commonly exposed to broad
      spectrum antimicrobial agents. Rates of resistance have increased for most
      pathogens associated with hospital-acquired infections among ICU patients, and
      rates are almost universally higher among ICU patients than non-ICU patients.
      Likewise, ICU patients hospitalized longer (i.e., >7 days) are two- to three-fold
      more likely to be infected with a pathogen possessing an antimicrobial-resistant
      phenotype of concern. However, there are many opportunities to prevent the
      emergence and spread of these resistant pathogens through improved use of
      established infection control measures (patient isolation, handwashing, glove
      use, and appropriate gown use) and implementation of a systematic review of
      antimicrobial use. (Crit Care Med 2001; 29[Suppl.]: N64-N68)

PMID- 11292879
TI  - Increasing threat of Gram-negative bacteria.
AB  - The widespread use of broad-spectrum antibiotics has led to emergence of
      antibiotic-resistant strains of many Gram-negative organisms. This problem is
      particularly serious in critically ill patients, especially those with ventilator
      associated pneumonia. Extensive antibiotic resistance has developed in Gram
      negative bacteria, due both to innate resistance in some species and the fact
      that they are highly adept at acquiring antibiotic-resistant determinants from
      each other. Antibiotic resistance develops through the following three basic
      mechanisms: alteration of the drug target, prevention of drug access to the
      target (including actively removing the drug from the bacteria), and drug
      inactivation. Certain Gram-negative microorganisms are particular problems in the
      intensive care unit, including Pseudomonas aeruginosa, Acinetobacter spp.,
      Stenotrophomonas maltophilia, and the Enterobacteriaceae. The combination of an
      increasing population at risk, and the natural virulence and adaptability of Gram
      negative bacteria guarantees that critical care physicians will face a persistent
      and increasing challenge from these pathogens.

PMID- 11292880
TI  - Impact of Gram-positive resistance on outcome of nosocomial pneumonia.
AB  - Among Gram-positive pathogens, Staphylococcus aureus is the leading cause of
      death from nosocomial pneumonia. The bacterium developed progressive resistance
      to beta-lactams, and methicillin-resistant strains emerged in the 1980s. In
      consequence, vancomycin has become the drug of choice for treatment of this
      infection over the last decade, based on susceptibility tests and the serum
      antimicrobial levels recorded. However, half of the patients treated with
      vancomycin have died. In contrast, in patients receiving beta-lactams for
      pneumonia caused by methicillin-sensitive S. aureus, survival is the rule. These
      observations, together with the emergence of isolates with reduced susceptibility
      to glycopeptides, raised concern about the use of vancomycin as standard therapy
      for pneumonia caused by Gram-positive cocci. Maintaining tissue levels above
      minimal inhibitory concentration is vital to successful clinical outcome.
      Optimizing treatment focusing on this goal and new antimicrobials provide new
      opportunities to improve survival. (Crit Care Med 2001; 29[Suppl.]:N82-N86)

PMID- 11292881
TI  - Using information systems technology to improve antibiotic prescribing.
AB  - The selection of antimicrobial agents in the hospital setting is still a largely
      manual task and, therefore, fraught with the potential for error. This includes
      the choice of agents, dosage regimens, and monitoring for response and toxicity.
      The authors describe current and future strategies to use information technology
      to improve the process of antimicrobial selection and to avoid dosing errors and
      contraindicated drug combinations. The possible role of decision support in
      preventing the emergence of resistance is also discussed.

PMID- 11292882
TI  - Evolving antimicrobial chemotherapy for Staphylococcus aureus infections: Our
      backs to the wall.
AB  - Staphylococcus aureus is responsible for many nosocomial and community-acquired
      infections. Its evolving resistance to traditional antimicrobial chemotherapy and
      emerging prevalence outside of the healthcare environment are serious concerns.
      This review of the changing epidemiology of methicillin-resistant S. aureus, the
      emergence of vancomycin (glycopeptide)-resistant isolates, and the mechanisms of
      resistance to beta-lactams and glycopeptides provides an update for clinicians
      regarding effective strategies for treatment.

PMID- 11292883
TI  - Antibiotic resistance in postoperative infections.

PMID- 11292884
TI  - Antimicrobial management strategies for Gram-positive bacterial resistance in the
      intensive care unit.
AB  - This article summarizes the current situation with Gram-positive infections,
      including the two primary consequences-failure to cure and resistance-relevant to
      the intensive care unit. The past few years have seen Enterococcus faecium
      resistance to vancomycin increase from 10% of strains to approaching 60% of
      strains in some centers. Failure is now so frequent that vancomycin can no longer
      be safely used. This has lead to use of two new antibiotics,
      quinupristin/dalfopristin (Synercid), first marketed in the United States in
      September 1999, and linezolid (Zyvox), which reached the U.S. market in May 2000.
      Both of these agents are being used to treat culture-proven vancomycin-resistant
      E. faecium. The calculated areas under the inhibitory curve (AUIC) values of
      vancomycin, even when its minimal inhibitory concentration (MIC) is 4.0
      microg/mL, show almost all vancomycin-resistant E. faecium have AUICs <125. This
      explains failure, as well as the further selection of this bacteria into
      subpopulations with progressively higher MICs. Less well defined, but potentially
      an even greater problem, is the poor efficacy of vancomycin against
      multiresistant Staphylococcus aureus. Here, there is evidence of clinical failure
      in lower respiratory tract infection patients, but in most cases the MIC values
      of the organism have not risen to the point where AUICs are <125. However, the
      minimum bactericidal concentration of this organism may be considerably higher
      than its MIC, and in other cases there may be a high inoculum effect or a protein
      binding effect to explain the failure of vancomycin to kill multiresistant S.
      aureus. Besides the increasing use of the new agents, strategies to manage these
      two increasingly resistant Gram-positive infections include cephalosporin
      restriction, switch and streamlining when cultures come back from the lab,
      combination regimens, and cycling in selected intensive care units.

PMID- 11292885
TI  - Intensive care unit antimicrobial resistance and the role of the pharmacist.
AB  - Over the past 20 yrs, pharmacists have successfully integrated their services and
      expertise to gain acceptance as full members of pediatric, surgical, medical, and
      intensive care unit (ICU) patient care teams. The pharmacists' training in
      pharmacology, pharmacokinetics, pharmacodynamics, and pharmacoeconomics
      complements the expertise of other members of the patient care team. Generally, a
      strong background in infectious diseases and critical care also provides a focal
      point for clinical pharmacy service intervention. Although practitioners often
      focus on issues exclusively related to their specific hospital or ICU, the issues
      surrounding antibiotic resistance are more global and societal in nature.
      Medical, surgical, and pharmaceutical practices inside the hospital and ICU
      extend their influence into the community. Customs and practices of daily living
      in our society coupled with use of agents capable of altering microbial flora
      impact our hospital and ICU when patients from the community are admitted. The
      misuse of antibiotics and the lack of effective infection control programs are
      often identified as key components in the perpetuation of these phenomena. The
      focus for the pharmacist and the ICU team must be on the optimization of
      antibiotic use and infection control guidelines. This review will address the
      many issues that surround the appropriate use of antibiotics and what role the
      pharmacist can play in ensuring the optimal use of infection control measures in
      the ICU and hospital.

PMID- 11292886
TI  - Impact of antibiotic resistance on clinical outcomes and the cost of care.
AB  - Antibiotic-resistant organisms are common in intensive care unit infection and
      can be either Gram-positive or Gram-negative. A number of studies have evaluated
      whether these organisms can lead to excess morbidity, mortality, or cost. In
      general, the studies are confounded by a number of methodologic issues, including
      the selection of an appropriate control population. Cases and controls must be
      appropriately matched for the presence of infection, the presence of infection
      with similar organisms (but ones that are either antibiotic-sensitive or 
      resistant), and severity of illness. In addition, studies must account for the
      therapies given to patients who are infected with resistant organisms because
      resistance is an important risk factor for inadequate empirical therapy, and such
      therapy is itself a potent determinant of a number of adverse outcomes, including
      mortality. To date, the data with methicillin-resistant Staphylococcus aureus and
      vancomycin-resistant enterococcus are inconsistent with regard to the effect on
      mortality rates, although infection with both organisms can lead to excess length
      of stay and increased cost of care. When studies have been adequately controlled
      and powered, infection with vancomycin-resistant enterococcus has had more of an
      effect on the mortality rate than infection with antibiotic-sensitive
      enterococci. Infection with resistant Gram-negatives also has adverse impact on
      outcome, with excess mortality being seen in patient groups infected with
      Acinetobacter and Pseudomonas aeruginosa. If we are to minimize the effect of
      resistance on medical outcomes and cost, it will be necessary to have a current
      knowledge of each intensive care unit's pathogens and susceptibility patterns, so
      that empirical therapy will have a good likelihood of being effective. In
      addition, new therapeutic agents may improve on the efficacy of older agents and
      could reduce cost if they allow for some patients to leave the hospital and to
      finish therapy with an oral formulation of a highly bioavailable agent.

PMID- 11292887
TI  - Antimicrobial management measures to limit resistance: A process-based conceptual
      framework.
AB  - To curb the trend toward increasingly resistant microorganisms, we must at least
      ensure that antibiotics are used in accordance with the best available scientific
      evidence. Here we review the control and streamlining measures aimed at
      optimizing the use of antibiotics, placing an emphasis on their demonstrated
      effectiveness in the intensive care unit environment. Because of their wide
      variety, the measures have been organized along the process of choosing, dosing,
      delivering, and then adjusting the initial antibiotics according to the culture
      results. By clarifying the range of options available, this process-based
      conceptual framework assists in best adapting a creative mixture of control
      measures to a particular healthcare system. The framework also facilitates the
      overview of a proposed multidisciplinary antibiotic management program, thereby
      helping to secure the administrative and local provider support necessary for its
      implementation and continued improvement.

PMID- 11292888
TI  - Infection control measures to limit antimicrobial resistance.
AB  - Increasing antimicrobial resistance has resulted in a rapidly decreasing array of
      therapeutic options for infections in the critical care setting. Reports of
      reduced susceptibility to vancomycin in Staphylococcus aureus raise the
      possibility of patients being infected with a virulent pathogen for which most
      antibiotics are ineffective. Infection control methods to contain resistance,
      exclusive of antimicrobial restrictions, focus on surveillance to identify
      carriers of resistant organisms, prevention of nosocomial infections, adequate
      hand hygiene, isolation of patients who harbor resistant organisms, and the use
      of barrier techniques such as gowns and gloves. Surveillance using clinical
      isolates alone is inadequate for the identification of the majority of patients
      who carry resistant organisms. However, it is unclear what intensity of
      surveillance is needed to control the spread of these organisms in the intensive
      care unit in nonoutbreak situations. Attempts at eradicating carriage are often
      unsuccessful when there is extranasal colonization with methicillin-resistant S.
      aureus. Transmission of resistant organisms is primarily the result of transient
      contamination of healthcare workers' hands. Adequate handwashing, isolation of
      carriers, and barrier techniques are all necessary for containing resistance
      within the intensive care unit, however, compliance with these measures can be
      compromised by high staff turnover and heavy workload.

PMID- 11292889
TI  - Is there a role for antibiotic cycling in the intensive care unit?
AB  - Antibiotic resistance of bacterial pathogens has emerged as one of the most
      important issues facing critical care practitioners. Resistance of many commonly
      encountered bacterial species is increasing and has been associated with greater
      administration of inadequate antimicrobial therapy to patients within intensive
      care units. This has resulted in greater patient morbidity, higher mortality
      rates, and increased healthcare costs. Methods to reduce antimicrobial resistance
      have focused on increasing adherence to infection control practices and improving
      antibiotic utilization. Antibiotic cycling is a strategy to reduce antimicrobial
      resistance by withdrawing an antibiotic or antibiotic class from use and
      subsequently reintroducing it at a later point in time. The main goal of cycling
      is to allow resistance rates for specific antibiotics to decrease, or at least
      remain stable, when their use is periodically eliminated from the intensive care
      unit.

PMID- 11292898
TI  - Effects of  Hot shot  on recovery after hypothermic ischemia in neonatal lamb
      heart.
AB  - BACKGROUND: Terminal warm blood cardioplegia, "Hot shot", is the method for
      providing an energy replenishment and/or early recovery of aerobic metabolism
      without electromechanical activity at initial reperfusion. The mechanism of
      beneficial effects of this  Hot Shot  is multifactorial. This study was designed
      to assess the effects of terminal warm blood cardioplegia by comparing with
      oxygenated terminal warm crystalloid cardioplegia. METHODS: In Group HS-B, n=8
      (oxygenated blood; 37 degrees C, Ht: 20%, K+ 20 mEq/l, pH 7.237, PO2 219 mmHg)
      and in Group HS-C, n=8 (bloodless oxygenated (5% CO2+95%O2) crystalloid, 37
      degrees C, K+ 20 mEq/l, pH 7.435, PO2 624 mmHg), terminal warm cardioplegia (20
      ml/kg for 5 minutes) was studied in the isolated blood perfused neonatal lamb
      heart following 2 hr of cardioplegic ischemia. Another eight hearts served as
      control without any kind of terminal cardioplegia. After 60 min of reperfusion,
      LV function was measured. Coronary blood flow (CBF), oxygen content, and oxygen
      consumption (MVO2) were measured and the oxygen extraction ratio was calculated
      in Group HS-B and HS-C during terminal cardioplegia and/or reperfusion. Results
      are given as % recovery of preischemic values. RESULTS: HS-B as well as HS-C
      groups showed better functional recovery in maximum developed pressure (DP:
      78.0+/-8.3 in HS-B vs 65.2+/-9.2%; p=0.018), maximum dp/dt (67.3+/-6.2 in HS-B,
      65.3+/-7.4 in HS-C vs 55.8+/-5.0%; p=0.003, p=0.02), DP V10 (87.1+/-8.5 in HS-B
      vs 67.2+/-9.9%; p=0.0001), and peak dp/dt V10 (76.4+/-7.6 in HS-B, 69.8+/-8.1 in
      HS-C vs 58.6+/-6.9 %; p=0.0001) than the control group. Between the HS-B and HS-C
      groups, HS-B showed better functional recovery in terms of DP V10 (p=0.01).
      Oxygen delivery of terminal cardioplegia was almost four times higher in HS-B
      group (90.4+/-17.7 vs 18.7+/-1.1 mcl/ml), contrarily, HS-C group showed four
      times higher oxygen extraction ratio compared to HS-B group (0.78+/-0.06 vs
      0.18+/-0.11), thus oxygen consumption during hot shot was maintained at the same
      level in both groups. CBF in the control group was lower than that in the other
      groups at 60 min of reperfusion. CONCLUSIONS: Reperfusion with both terminal warm
      cardioplegia including blood and oxygenated crystalloid cardioplegia resulted in
      better recovery of function and higher levels of CBF with slightly better
      function in terminal warm blood cardioplegia.

PMID- 11292900
TI  - Homologous monocuspid valve patch in right ventricular outflow tract
      reconstruction.
AB  - BACKGROUND: In the surgical repair of tetralogy of Fallot or pulmonary atresia,
      pulmonary regurgitation may be detrimental in the postoperative period. We have
      used homograft monocuspid valve patch to prevent pulmonary insufficiency.
      METHODS: From September 1996 to December 1998, twenty-five patients, 4 months to
      8 years of age (median 10.1 months) had homograft monocuspid valve in the
      procedure of right ventricular outflow tract reconstruction. The function of the
      monocuspid valve was assessed by echocardiogram and graded as trivial to mild,
      mild to moderate, moderate, and severe. We evaluated the degree of pulmonary
      insufficiency before discharge, at 3-6 months, and at 12 months after the
      operation. RESULTS: There was one hospital death due to fulminate adeno viral
      pneumonia. On echocardiogram, 21 patients (88%, 21/24) had no significant
      pulmonary insufficiency. Only one patient (4.5%) showed a moderate degree of
      pulmonary insufficiency. At 3-6 months, seventeen of twenty-one (81%) patients
      had no significant pulmonary insufficiency. There were fourteen patients who had
      follow-up over 1 year, and no patients showed newly developed significant
      pulmonary insufficiency. CONCLUSIONS: We concluded that the homograft monocuspid
      valve patch for right ventricular outflow tract reconstruction has provided
      excellent early results for the prevention of pulmonary insufficiency. However
      these effects are limited in duration and further close follow-up should be
      needed.

PMID- 11292899
TI  - Differences in adaptation to growth of children between internal thoracic artery
      and saphenous vein coronary bypass grafts.
AB  - BACKGROUND: It is not known how the internal thoracic artery (ITA) and saphenous
      vein graft (SVG) adapts to somatic growth of pediatric patients who underwent
      coronary artery bypass grafting (CABG). METHODS: Twenty-two ITAs and 6 SVGs in 17
      patients who underwent at least three postoperative catheterizations with
      biplanar cineangiography and followed for a minimum of 5 years were evaluated. We
      evaluated the length, diameter and curvature of the grafts by cineangiographies
      which were performed at 1 month, 1 year, 5 years and more than 5 years
      postoperatively. RESULTS: The length of the ITA (1-month: 117+/-31 mm, 1-year:
      134+/-32 mm, 5-years: 146+/-28 mm, and >5-years: 155+/-34 mm, p=0.032) and
      diameter of the ITA (1.4+/-0.4 mm, 2.0+/-0.7 mm, 2.3+/-0.6 mm and 2.6+/-0.6 mm,
      p<0.0001) significantly increased over time, but neither the length nor diameter
      of the SVG length: 121+/-33 mm, 119+/-29 mm, 119+/-25 mm and 126+/-1 mm,
      p=0.9907; diameter: 4.1+/-1.0 mm, 3.9+/-0.7 mm, 4.0+/-0.8 mm and 3.3+/-0.4 mm,
      p=0.5784) increased. Although the ITA exhibited no change in curvature over time
      (1 month: 1.15+/-0.07, late: 1.15+/-0.07, p=0.8490), the curvature of the SVG
      significantly decreased over time (1 month: 1.42+/-0.19 and late: 1.25+/-0.16,
      p=0.0277). The percent segmental length of ITAs were changed little from early to
      late after CABG (1 month: proximal: 33.7+/-7.0%, middle: 33.3+/-7.9% and distal:
      32.9+/-7.9%, vs late: 34.3+/-7.2%, 33.2+/-7.9% and 32.5+/-7.9%, p=0.937).
      CONCLUSIONS: ITAs grow in proportion to somatic growth, while SVGs course in a
      more linear fashion in adapting to patient growth.

PMID- 11292901
TI  - Surgical myocardial revascularization (CABG) in patients with pulmonary disease:
      beating heart versus cardiopulmonary bypass.
AB  - BACKGROUND: Adverse effects on the respiratory system can be severe in many
      instances after coronarv artery bypass grafting (CABG) with cardiopulmonary
      bypass (CPBP). Recently, operative techniques without CPBP have gained widespread
      consent, thanks to the newly developed retractors that allow satisfactory
      immobilisation of the surgical field. METHODS: Thirty-seven patients operated
      upon in our Institution between April 1997 and April 1998 showed an obstructive
      and/or restrictive pulmonary disease. Twenty-one patients were operated on
      without CBPB (group A), while 16 patients were operated using CPBP (group B,
      control). The allocation in each group had been randomised. RESULTS: The length
      of the operation in group A was less than in group B (196+/-35 minutes vs 235+/
      60 minutes), (p=0.014). A significant difference was found in postoperative
      bleeding: 562+/-381 ml vs 776+/-378 (p=0.046), in postoperative red cell count,
      hemoglobin level and Hct. Permanence on the ventilator was 19.1+/-13 hours in
      group B and 13.1+/-6.1 hours in group A (p=0.03). The length of stay in ICU was
      significantly different: 33.8+/-16.2 hours for group A vs 53.6+/-29.3 hours for
      group B (p=0.01). No respiratory failure occurred in group A; two patients
      experienced slow weaning from ventilation assistance and one died from that
      complication in group B. CONCLUSIONS: Myocardial revascularization without CPBP
      allows a better postoperative clinical course in patients with advanced pulmonary
      disease.

PMID- 11292903
TI  - Plasma magnesium in patients submitted to cardiac surgery and its influence on
      perioperative morbidity.
AB  - BACKGROUND: To determine the changes in magnesaemia in cardiac surgical patients
      submitted to cardiopulmonary bypass (CPB) and their influence on perioperative
      morbidity. METHODS:  SETTING: the cardiovascular surgery department of a
      university hospital. PATIENTS: 60 patients of both sexes, mean age 60+/-12 yrs,
      operated on consecutively for myocardial revascularization or valve replacement.
      INTERVENTIONS: plasma Mg2+ levels were measured preoperatively, during CPB,
      postCPB and throughout the first 24 hrs after operation. Preoperative plasma Mg2+
      levels of these patients were compared with those of 15 non-cardiac surgical
      patients and 11 healthy volunteers. RESULTS: Mean values of Mg2+ similar in the
      three populations although in the group of cardiac patients the number of
      hypomagnesaemic patients was significantly higher (16 patients=26.6%). In these
      16 patients, preoperative hypomagnesaemia had a statistically significant
      relationship with the preoperative treatment with beta-blockers and previous
      history of arrhythmias (p<0.05). A progressive statistically significant decrease
      of Mg2+ was observed throughout the surgery that remained low at 24 hours
      postoperatively (p<0.05). Normomagnesemic patients needed significantly more
      shocks and electrical energy to obtain heart defibrillation after CPB. The
      incidence of both postoperative arrhythmias and postoperative low cardiac index
      (<2.5 L.m2) was statistically significantly more frequent in hypomagnesaemic
      patients (p<0.05). CONCLUSIONS: Preoperative hypomagnesaemia was more frequent in
      this small sample of cardiac surgical patients than in non-cardiac surgical
      patients and was related to preoperative treatment with b-blockers. Hypomagne
      saemia caused by CPB persisted 24 hrs after operation and was associated with
      higher incidence of both postoperative arrhythmias and low cardiac index.

PMID- 11292902
TI  - Limitation of infarct size by fixed coronary arterial stenosis maintained during
      reperfusion.
AB  - BACKGROUND: The effect on infarct size of a pre-infarction high-grade, fixed
      coronary arterial stenosis maintained during reperfusion, was evaluated. METHODS:
      This experimental study was carried out in the research laboratory of a
      University Hospital. A canine occlusion-reperfusion model was used. Twenty-eight
      dogs underwent proximal left anterior descending (LAD) coronary artery occlusion
      (O). In Group 1 (n=6) the O lasted for 6 hours. In Group 2 (n=6) the O lasted for
      2 hours followed by 4 hours of reperfusion (R). In Group 3 (n=3), LAD was
      stenosed for 30 minutes followed by O for 6 hours. In Group 4 (n=7) LAD was
      stenosed for 30 minutes followed by O for 2 hours and then 4 hours of R during
      which the artery was kept stenosed at the same degree (fixed) as the initial one.
      In Group 5 (n=6) the protocol was identical to Group 4 with the additional use of
      the intra-aortic balloon pump during R. RESULTS: The infarcted myocardium was
      almost the same in Groups 1 and 3 (80.0+/-10.6% vs 77.3+/-3.8%, respectively,
      p=NS), but less in Group 2 (59.0+/-19.9%, p=0.046 vs Group 1). There were no
      hemodynamic differences between Groups 4 and 5 and the infarcted myocardium was
      almost identical in both groups (37.7+/-18.8% and 38.7+/-19.1%, respectively,
      p=NS). The combined results of Groups 4 and 5, regarding the infarcted
      myocardium, was 38.1+/-18% (p=0.037 vs Group 2). CONCLUSIONS: In this acute
      coronary occlusion model, a pre-existing high-grade stenosis that maintained
      during reperfusion increased the amount of salvaged ischemic myocardium.

PMID- 11292904
TI  - Protective effect of lisinopril against ischemia-reperfusion injury in isolated
      guinea pig hearts.
AB  - BACKGROUND: In order to determine whether angiotensin-converting enzyme
      inhibitors (ACEI s) attenuate ischemia-reperfusion injury, we investigated and
      compared the effects of lisinopril via different routes of administration in an
      isolated guinea pig heart model of ischaemia reperfusion. METHODS: The effect of
      lisinopril cardioplegia, oral pretreatment with lisinopril and lisinopril
      enriched reperfusion solution on myocardium after a normothermic global ischemia
      of 90 minutes and 30 minutes of reperfusion in the modified Langendorff model was
      randomly studied in 4 groups (n=8 in each). In all groups, cardioplegic arrest
      was achieved by administering St. Thomas Hospital Cardioplegic Solution (STHCS).
      The first group was utilized as the control. In the second group, hearts were
      arrested with lisinopril (1 micromol/L) enriched STHCS. In the third group,
      animals were pretreated with oral lisinopril (0.2 mg/kg/twice a day) for ten
      days. In the last group hearts were again pretreated with oral lisinopril (like
      in Group 3) and the heart were reperfused with lisinopril enriched (1 micromol/L)
      Krebs-Henseleit solution during the reperfusion period. RESULTS: Contractility,
      which was expressed as contractile force (g contractility/g heart weight), was
      preserved better in the study groups. In the last group, the hearts had the best
      left ventricular contractile function, where contractile force was 58.4%+/-4.82%
      of the preischaemic values. In Group I, Group II and Group III they achieved
      29.5%+/-5.6%, 41.9%+/-4.9%, and 55.3%+/-5.8% of their preischaemic contractile
      force values respectively. Creatine kinase leakage was significantly lower and
      also post- ischaemic coronary flows were significantly higher in the 4th group.
      Coronary flow after reperfusion increased from 48.0+/-6.2 to 68.0+/-4.51
      ml/min.g.heart, in Group IV (p<0.05). CONCLUSIONS: Myocardial MDA and GSH
      contents showed that there was a correlation between the depletion of myocardial
      GSH content and increased lipid peroxidation. The myocardial GSH content
      indicates that the best results were obtained in the last group as compared to
      the other groups. These preliminary results showed that oral preconditioning
      improved postischaemic myocardial function and decreased myocardial injury.
      Because the best results were achieved in the last group, it can be suggested
      that lisinopril may also play a protective role against reperfusion injury.

PMID- 11292905
TI  - Patch repair of postinfarction pseudo- and subepicardial aneurysm of the left
      ventricle.
AB  - Left ventricular pseudo-aneurysm and subepicardial aneurysm are rare
      complications of myocardial infarction. However, the prognosis of medical
      treatment is extremely poor and the operative procedure is controversial. We
      experienced 3 consecutive patients with this unusual left ventricular aneurysm,
      and described the clinical presentation, operative procedure and its result in
      these patients. The interval from myocardial infarction to discovering aneurysmal
      formation is short. The term was within a month. In all patients, the papillary
      muscle was in the proximity of the orifice of the aneurysm. Patch repair of these
      unusual left ventricular aneurysms may be effective for improvement of left
      ventricular function without mitral regurgitation.

PMID- 11292906
TI  - Primary cardiac leiomyosarcoma originating from the pulmonary valve. Case report
      and review of the literature.
AB  - Primary cardiac tumours are rare findings (incidence 0.02% according to a recent
      meta-analysis) with dismal prognosis. Approximately 25% are malignant, mostly
      represented by sarcomas. Among these, leiomyosarcomas are exceptional. Treatment
      for primary cardiac leiomyosarcomas consists of radical surgical resection
      followed by adjuvant radiation therapy and/or chemotherapy. The mean survival
      after surgery and adjuvant therapies is 6.8 months. We present a rare case of a
      40- year-old male patient with a primary cardiac leiomysarcoma originating from
      the pulmonary valve. This patient died after surgery and implantation of a
      homograft of the pulmonary trunk. Furthermore, the literature has been reviewed.

PMID- 11292907
TI  - Perioperative myocardial infarction in a patient with tuberculous constrictive
      pericarditis in the absence of coronary artery disease.
AB  - A 34-year-old man developed severe heart failure due to constrictive
      pericarditis. Pericardiectomy was carried on and the patient died 12 hours after
      surgery. Necropsy revealed an extensive hemorrhagic myocardial infarction
      involving the lateral free wall of the left ventricle in the absence of coronary
      artery disease. In addition, necropsy revealed tuberculosis as the etiology of
      constrictive pericarditis. Thus, myocardial infarction may occur in constrictive
      pericarditis in the setting of pericardiectomy and absence of coronary artery
      disease.

PMID- 11292908
TI  - Angiographic evidence of thrombosis after off-pump coronary surgery. A case
      report.
AB  - We report the case of a patient who underwent off-pump coronary surgery, whose
      postoperative (3 days) angiography showed the presence of a thrombus in the left
      internal mammary artery. The thrombus responded to an aggressive anticoagulant
      treatment, showing a perfect angiographic result 15 months later. According to
      our previous studies, we suggest that an adequate anti-coagulant treatment should
      be undertaken for patients undergoing off-pump coronary surgery in the early
      postoperative period.

PMID- 11292909
TI  - A coronary aneurysm complicated by acute myocardial infarction. A case report.
AB  - Coronary artery aneurysm (CAA) is a relatively rare disease that may cause
      angina, myocardial infarction, sudden death due to thrombosis, embolisation, or
      rupture. This report describes the case of a man aged 65 years old who had an
      anterior myocardial infarction due to left anterior descending artery (LAD)
      aneurysm. We attempted early percutaneous transluminal coronary angioplasty
      (PTCA) for treatment of acute myocardial infarction, but were not successful. He
      was then treated with intracoronary streptokinase. Serial coronary angiographies
      showed recanalisation and aneurysm on the LAD. The patient was operated on with
      coronary bypass surgery, and treated with an oral anticoagulant, nitrate, and
      blocker. He was well after one year of follow-up.

PMID- 11292910
TI  - Intravascular ultrasound for iliac artery imaging. Clinical review.
AB  - IVUS is able to produce trans-sectional images of the iliac arteries at a high
      resolution. The three layered appearance of the arterial wall can be visualized.
      In the atherosclerotic diseased artery calcified plaques can be discerned from
      non-calcified plaques, and the distribution of the plaque-eccentric or concentric
      can be determined. IVUS seems to be superior to arteriography in quantifying the
      degree of stenosis, being able to relate the luminal area to the mediabounded
      area at the same site of the artery. The discrepancy between IVUS and
      arteriography is even greater when evaluating residualstenosis after PTA.
      Structures such as rupture, intimal flaps and dissection are better visualized
      with IVUS. In stenotic iliac arteries IVUS has been able to evaluate the effect
      of PTA and stenting and relating the effect to the morphology of the plaque. IVUS
      measurements seem to be important predictors of the patency of iliac PTA. The
      ability of IVUS to evaluate the adaptation of stents to the arterial wall makes
      it particularly suited as a control procedure for the deployment of endovascular
      stented grafts. Finally IVUS has the ability to disclose insufficiency of
      endarterecomy, by visualizing remaining intraluminal material.

PMID- 11292911
TI  - Endovascular treatment of aortic rupture by blunt chest trauma.
AB  - BACKGROUND: The usual treatment of blunt aortic injury (BAI) is prompt surgery.
      Frequently severe injuries to the brain or lungs exclude further surgical
      treatment. The purpose of this study is to assess the feasibility of placing
      endovascular stent-grafts. METHODS: From 1992 through 1999, in our primary and
      referral trauma center, 26 acute BAI, 21 males and 5 females, mean age 40.2+/
      16.3 yrs were diagnosed. The last 4 patients underwent prospectively endovascular
      repair with Talent endograft. Endoprosthesis parameters were measured on three
      dimensional spiral CT reconstruction. While waiting for devices, blood pressure
      was aggressively lowered and aortic lesions were monitored by transesophageal
      echography. RESULTS: Stent-graft deployment was successful in all 4 patients.
      There were no complications of endoleak, stent migration, paraplegia or death.
      Angiographic exclusion was complete in all 4 patients. CT scans at a mean follow
      up of 11+/-5 months showed complete healing of the aortic wall in all patients.
      CONCLUSIONS: For stable acute BAI, endovascular stent-graft repair is feasible
      and safe, and is an effective therapeutic alternative to open surgery. Because of
      the normal proximal and distal wall in aortic injuries, endoluminal treatment
      might be the therapy of choice in the near future.

PMID- 11292912
TI  - Endovascular venous stenting in May-Thurner syndrome.
AB  - BACKGROUND: Chronic pulsatile compression of the left common iliac vein between
      the crossing right common iliac artery and the lowest lumbar vertebral body may
      induce focal intimal proliferation of the vein (May-Thurner syndrome), resulting
      in impaired venous return and left iliofemoral thrombosis. Corrective surgical
      treatment requires extensive dissection. In this report, we describe our
      experience with endovascular venous stenting in May-Thurner syndrome. METHODS:
      Six patients with symptomatic May-Thurner syndrome were treated with percutaneous
      transluminal angioplasty and implantation of self-expanding stents. RESULTS
      Postprocedure phlebography revealed patent iliofemoral veins with unimpeded
      venous outflow and disappearance of collaterals in all patients. No procedure
      related complications occurred. At follow-up (median, 12 months), 5 of 6 patients
      were free of symptoms. In one patient lower extremity edema was aggravated
      despite a patent stented segment of the left iliac vein. The patient continues to
      wear support stockings to compensate for continuing venous insufficiency. Color
      coded duplex scanning revealed patency at regular intervals in 5 patients. In one
      patient, occlusion of the stented venous segment with return of symptoms was
      detected at one month. Patency could not be restored despite catheter-directed
      thrombolytic therapy. After angioplasty, however, adequate collateral circulation
      was restored and symptoms resolved completely. CONCLUSIONS: Endovascular venous
      stenting in May-Thurner syndrome is technically feasible, and leads to reduction
      of symptoms in the majority of patients with high patency rates in the medium
      term. This approach may prove to be a percutaneous alternative to surgical
      treatment.

PMID- 11292914
TI  - Treatment of ruptured anastomotic aneurysm by endograft.
AB  - Ruptured anastomotic aneurysms after aortobifemoral surgery are potentially life
      threatening. The preferred technique consists of resection of the pseudoaneurysm
      and interposition of a new graft. We present a case in which an endovascular
      approach was chosen for treatment of a ruptured femoral false aneurysm. An
      endograft was inserted and complete exclusion of the pseudoaneurysm was achieved.

PMID- 11292913
TI  - Preoperative dipyridamole-thallium scanning, selective coronary revascularization
      and long-term survival in patients with critical lower limb ischemia.
AB  - BACKGROUND: A large proportion of patients with critical limb ischemia have
      advanced, often asymptomatic coronary artery disease which is associated with
      increased perioperative risk and decreased long-term survival. METHODS: We
      evaluated retrospectively the short and long-term effect of routine dipyridamole
      thallium cardiac scanning (DTS) and selective coronary revascularization in 113
      consecutive patients who were scheduled for revascularization of the lower
      extremity. RESULTS: DTS was abnormal in 60 (53.1%) patients and demonstrated a
      moderate-severe reversible defect in 26 (23.0%) patients. On the basis of DTS and
      clinical evaluation 33 (29.2%) patients were referred for coronary
      catheterization. Of these, 9 underwent PTCA and 4 underwent coronary artery
      bypass, without complications. Surgical revascularization of the limbs was
      performed in all but two patients. Two (1.8%) patients died postoperatively,
      three (2.7%) sustained nonfatal postoperative myocardial infarctions. None of the
      patients who underwent preoperative coronary revascularization suffered a cardiac
      complication after the peripheral vascular operation. During mean follow-up of
      31.7 months, 30 (28.0%) patients died. A moderate-severe reversible defect on DTS
      was the strongest predictor for shortened survival (Exp(b)=0.61, CI 95%=0.42
      0.88; p=0.006). Patients who underwent preoperative coronary revascularization
      followed a survival curve approaching those without a reversible defect on DTS
      (mean survival 61+/-8 vs 63+/-4 months; NS) which was significantly better than
      those with such a defect who did not undergo coronary revascularization (mean
      survival 34+/-5 months; p=0.03). CONCLUSIONS: While the perioperative benefits of
      routine preoperative DTS screening in patients with critical limb ischemia,
      remain debatable, it provides an opportunity for identification and treatment of
      life-limiting coronary artery disease and improving survival.

PMID- 11292915
TI  - Transient relief of abdominal angina by Wallstent placement into an occluded
      superior mesenteric artery.
AB  - A 56-year-old man presented with complete occlusion of the superior and inferior
      mesenteric arteries resulting in chronic mesenteric ischemia. After a minimal
      angioplasty a Wallstent was inserted across the superior mesenteric artery
      occlusion. This produced immediate clinical relief, with a successful
      angiographic result. Eight months later, an intrastent occlusion with acute bowel
      infarction was treated in emergency by saphenous vein bypass graft. Despite the
      death of the patient a few days later from a multivisceral failure syndrome, this
      method seemed to us feasible in treating a chronically occluded SMA in patients
      with high operative risk.

PMID- 11292916
TI  - Subclavicular trans-sternal approach to treat subclavian artery aneurysm. Case
      report.
AB  - Subclavian artery aneurysms are relatively rare, and the surgical approach
      depends on the location (intrathoracic or extrathoracic) and size of the
      aneurysm. Right subclavian artery aneurysms are usually operated upon using a
      supraclavicular approach or median sternotomy incision with right supraclavicular
      extension. We treated a right intrathoracic subclavian artery aneurysm by
      subclavicular trans-sternal approach. This surgical approach is recommended for
      treatment of right intrathoracic subclavian artery aneurysms for its easy access
      and excellent cosmetic results.

PMID- 11292917
TI  - Acute thrombosis of an aortic aneurysm.
AB  - The natural history of abdominal aortic aneurysms is to enlarge gradually.
      Associated complications are rupture, peripheral embolization and infection.1-5
      Complete occlusion of an abdominal aortic aneurysm by thrombus is extremely rare
      and constitutes a surgical emergency, with an estimated mortality of 50%.1-5 We
      report a case of a patient with this very uncommon complication of abdominal
      aortic aneurysm and review the literature discussing its optimal identification
      and management.

PMID- 11292918
TI  - Pelvic arteriovenous malformation with iliac vein thrombosis. A case report.
AB  - BACKGROUND: Congenital arteriovenous malformations (AVMs) of the pelvis are
      relatively rare and are difficult to treat because of diffuse extension and the
      number of feeding vessels. METHODS: We describe a patient with a pelvic AVM with
      shunts who also developed iliac vein thrombosis. The AVM was diagnosed during
      evaluation of what had initially appeared to be a venous stasis ulcer. RESULTS:
      The ulcer was successfully treated by Palma s procedure, partial resection of the
      feeding vessels, and transcatheter arterial embolization. CONCLUSIONS:
      Coexistence of a pelvic AVM with an iliac vein thrombosis has not previously been
      reported.

PMID- 11292919
TI  - Mediastinal lymph node evaluation by computed tomographic scan in lung cancer.
AB  - BACKGROUND: Computed tomography (CT) has been widely used for preoperative
      mediastinal lymph node evaluation in lung cancer. But its accuracy has remained
      controversial. We studied the predictability of N-staging by CT scan. METHODS:
      From 1981 to 1996, 546 patients had preoperative CT scan and underwent a surgical
      resection with mediastinal lymph node dissection for primary pulmonary
      adenocarcinoma and squamous cell carcinoma. Nodes larger than 1.0 cm at short
      axis were considered abnormal. The discrepancy between clinical and pathologic
      findings in N factor was analyzed. RESULTS: Sensitivity (ST), specificity (SP)
      and accuracy (AC) were 33.0%, 90.4% and 78.9%, respectively. No statistically
      significant difference in the results is detected for individual years or types
      of scanning device. There were statistically significant differences as follows:
      ST and SP by histologic type, SP by gender, SP and AC by tumor size, SP by
      Brinkman index, ST by tumor location, and AC by serum CEA value. CONCLUSIONS: We
      should pay attention to false positive nodes in heavy smokers (or males), and
      positive nodes in adenocarcinoma, tumor larger than 3 cm or rising of serum CEA
      value, regardless of negative lymph node on CT scan.

PMID- 11292920
TI  - Experience with fatal interstitial pneumonia after operation for lung cancer.
AB  - BACKGROUND: The number of patients with lung cancer is increasing. This study was
      undertaken to realize the probability, fate and management of acute fatal
      postoperative complications. Since interstitial pneumonia was one of the most
      fatal postoperative complications, to know its incidence and fate is very
      important. METHODS: A total of 2667 patients who underwent thoracotomy caused by
      malignant tumors during the past 17 years were reviewed and studied. We performed
      investigations on medical records, chest X-rays, whole-body CT films, operative
      records and pathological specimens for all inpatients. RESULTS: Nineteen patients
      died in hospital 30 days after thoracotomy (operative death). Nine patients died
      in hospital more than 31 days after thoracotomy (hospital death). Eight cases out
      of 28 patients (operative and hospital deaths) developed and finally died by
      interstitial pneumonia. Each case was treated with steroids, neutrophil-elastase
      inhibitor, and/or immunosuppressive agents. These patients could not be selected
      by any preoperative laboratory examination, such as preoperative pulmonary
      function tests, serum biochemistry tests, and chest X-ray or CT films.
      Interstitial pneumonia as a complication of postoperative stage, was fatal and
      once developed, it was very difficult to save their lives. CONCLUSIONS: Since we
      reported the cases who died from acute postoperative complications, especially
      interstitial pneumonia, we could not present effective management. However, in
      this report, several therapeutic trials that may solve the problems of acute
      postoperative interstitial pneumonia were proposed.

PMID- 11292921
TI  - Aortico-pulmonary paraganglioma associated with bilateral carotid body tumors.
      Diagnostic presentation and clinical implications.
AB  - A case of mediastinal paraganglioma in association with bilateral carotid body
      tumors is presented. Characteristic radiological findings included a hypointense
      signal in T1-weighted, a hyperintense signal in T2-weighted magnetic resonance
      (MR) images and a vascular enhancement pattern in dynamic contrast enhanced MR
      imaging. Thus, feeding vessels could be depicted noninvasively. The importance of
      family screening in affected individuals is stressed, as a hereditary form of the
      disease exists in which multiple paragangliomas are common.

PMID- 11292922
TI  - Staged resection of bilateral pleuropulmonary blastoma in a two-month old girl.
AB  - Pleuropulmonary blastoma is a rare unilateral intrathoracic tumor of childhood.
      We report an unusual case of bilateral pleuropulmonary blastoma in a two-month
      old girl who underwent staged thoracotomies for complete wedge resection of both
      neoplasm. She remains well and tumor free two years after the operation.

PMID- 11292923
TI  - Curative resection of both primary and second primary lung cancer.
AB  - Curative resection of a second primary lung cancer in a patient who survived
      small-cell lung cancer is reported. Small-cell cancer had been treated with
      chemotherapy followed by surgical resection 12 years before. The patient
      developed squamous cell cancer as the second primary tumor and underwent
      lobectomy with mediastinal node dissection. Patients who undergo two curative
      pulmonary resections of both primary and second primary lung cancer are extremely
      rare. The patient is alive 176 months after the initial diagnosis of small-cell
      lung cancer and 28 months after resection for his second primary lung cancer.
      Careful follow-up at an interval of 3-6 months beyond 10 years is very important
      because adequate treatments could lead to longer survival of patients with
      primary small-cell lung cancer.

PMID- 11292924
TI  - Successful use of intraoperative radiotherapy for local control of an Askin's
      tumor recurrence.
AB  - Askin s tumor is an infrequent disease, with a high tendency to local recurrence.
      We present the case of a 16-year-old female diagnosed with a new recurrence of
      this tumor affecting the thoracic wall. There had been a previous 5-year history
      of 3 local recurrences treated each time by apparently complete surgery. A
      multidisciplinary approach consisting of chemotherapy, complete chest tumor
      resection and intraoperative radiotherapy was undertaken. After 2-year follow-up,
      the patient is alive and free of disease. The role of surgery is still the key to
      obtaining good survival, but in this case intraoperative radiotherapy proved to
      be a good adjuvant treatment.

PMID- 11292925
TI  - Unusually located hydatid cysts miming a pulmonary tumor invaliding the spine.
AB  - Hydatid disease is a worldwide encountered zoonosis but at present very rare in
      Europe, liver and lungs being the most frequently involved sites. Bone
      involvement is very uncommon and the vertebral spine is the most common site of
      skeletal involvement (less than 1% overall). We report a case of vertebral
      hydatid disease with secondary pleuro-pulmonary involvement successfully treated
      by emergency spinal decompression followed by lung resection en bloc with chest
      wall and partial vertebrectomy.

PMID- 11292926
TI  - Transient paraplegia following elective infrarenal aortic aneurysm repair.

PMID- 11292927
TI  - Effect of coronary artery bypass grafting on native coronary artery stenosis.
      Comparison of internal thoracic artery and saphenous vein grafts.
AB  - BACKGROUND: The purpose of this study was to investigate the influence of
      coronary artery bypass grafting on the degree of stenosis of the native coronary
      artery. METHODS:  EXPERIMENTAL DESIGN: retrospective data analysis. SETTING:
      University hospital. PATIENTS: consecutive patients undergoing coronary artery
      bypass grafting (n=52). Bypasses using internal thoracic artery grafts (n=26) and
      saphenous vein grafts (n=37) to incompletely occluded coronary arteries were
      studied. INTERVENTIONS: coronary artery bypass grafting using internal thoracic
      artery or saphenous vein grafts. MEASURES: stenosis of the native coronary artery
      on angiography. RESULTS: Three recipient coronary arteries bypassed with internal
      thoracic artery grafts (12%) and 14 recipient coronary arteries bypassed with
      saphenous vein grafts (38%) showed progression of narrowing (p=0.024). Two
      recipient coronary arteries bypassed with internal thoracic artery grafts (8%)
      and 13 recipient coronary arteries bypassed with saphenous vein grafts (35%)
      showed total occlusion (p=0.016). Hypertension, hyperlipidemia, diabetes
      mellitus, and smoking history did not correlate with progression of stenosis of
      the native coronary arteries. Graft flow measured during surgery in the saphenous
      vein grafts was not significantly different between the group that exhibited
      progression of the native stenosis and the group that did not. CONCLUSIONS:
      Coronary artery bypass grafting with saphenous vein grafts may result in
      progression of stenosis of the recipient coronary artery. This is less likely
      after coronary artery bypass grafting with internal thoracic artery grafts. This
      difference may be due to the ability of the pedicled internal thoracic artery
      graft to regulate flow. Thus competitive flow in the native coronary artery is
      minimized. This has significant clinical implications.

PMID- 11292928
TI  - Physical activity, symptoms of chest pain and dyspnea in patients with ischemic
      heart disease in relation to age before and two years after coronary artery
      bypass grafting.
AB  - BACKGROUND: To describe limitation of physical activity, cause of limitation of
      physical activity and symptoms of dyspnea and chest pain in relation to age
      before and 2 years after coronary artery bypass grafting (CABG). METHODS: All
      patients from Western Sweden who underwent CABG without concomitant procedures
      during 3 years in 1989-1991 answered questionnaires before, and 2 years after the
      operation. Patients were divided into 3 age groups of equal size i.e. 32-59
      years, 60-67 years and > or = 68 years. RESULTS: In total, 2121 patients
      participated in the evaluation. The overall 2 year mortality in the 3 age groups
      was 3.8%, 6.8% and 12.2% (p<0.001). Limitation of physical activity was
      significantly associated with age prior to surgery but not thereafter.
      Improvement in physical activity, following CABG, was significant in all age
      groups. The proportion of patients being free of dyspnea increased markedly
      regardless of age. The number of chest pain attacks was associated with age after
      CABG, i.e. fewer attacks in the elderly, but such an association was not found
      prior to surgery. Improvement in number of chest pain attacks was more marked in
      the elderly. CONCLUSIONS: Physical activity improved similarly in all age groups
      after CABG. Attacks of chest pain, although significantly reduced in all age
      groups, seemed more effectively reduced in the elderly.

PMID- 11292929
TI  - The Batista procedure. Theoretical analysis and clinical implications.
AB  - BACKGROUND: The Batista procedure leads to dramatic early improvement in left
      ventricular function in some patients and a worsening in function in others. The
      theoretical and actual clinical effects of the procedure on early postoperative
      left ventricular function remain controversial. The purpose of this study is to
      utilize an appropriate mathematical model to determine the effects of the Batista
      procedure on stroke volume and myocardial wall stress. Our hypothesis is that the
      preoperative end-systolic stress (ses) is an important predictor of early
      postoperative myocardial function after this procedure. A corollary is that an
      index related to ses may be useful in selecting patients for this procedure.
      METHODS: An analysis of the Batista procedure is developed, based upon a
      spherical membrane model of the ventricle. This model shows how ventricular
      dilatation distorts the systolic and diastolic pressure-volume relations.
      RESULTS: Dilatation initially improves ventricular performance; but further
      dilatation, beyond a critical value, produces an unstable state with sharply
      falling performance. For a ventricle operating significantly beyond the point of
      critical dilatation, our theoretical results suggest that the Batista procedure
      not only reduces myocardial stress but may improve stroke volume. The end
      systolic stress, ses is an indicator of how close a ventricle is to the critical
      dilatation point. CONCLUSIONS: There is a theoretical basis for the Batista
      procedure. Resection of myocardium not only decreases wall stress but may improve
      stroke volume for sufficiently dilated and depressed ventricles. Patients with
      markedly elevated end-systolic stress may benefit most from the Batista
      procedure.

PMID- 11292931
TI  - A comparison of ischemic preconditioning versus terminal warm cardioplegia with
      controlled reperfusion in open heart operation.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of three
      different methods of cardioprotection in patients undergoing valve replacement.
      METHODS: Ninety patients undergoing elective valve replacement were randomly
      divided into three groups. In group 1 (n=30), the patients received intermittent
      cold blood cardioplegia. In group 2 (n=30) they received terminal warm
      cardioplegia and controlled reperfusion, and in group 3 (n=30), the patients
      received two cycles of ischemia (2 minutes) and reperfusion (3 minutes) before
      heart arrest induced by cold blood cardioplegia. The parameters of cardiac
      function, creatine kinase MB, and clinical outcomes were recorded to assess the
      effects of experiment. RESULTS: The major preoperative and intraoperative
      variables are comparable within the three groups. The number of patients
      requiring the support of inotropic agents was 70% (21/30), 33% (11/30) and 40%
      (12/30) in group 1, 2 and 3, respectively (p<0.05). The doses of inotropic agent
      in groups 2 and 3, were significantly lower than in group 1 (1.5+/-0.3 and 1.8+/
      0.4 versus 4.5+/-0.8 microg x kg x min(-1), p<0.01) during the first 24 hours
      after operation. Two deaths (30 day-hospital mortality) occurred, one in group 1
      and one in group 2. The cardiac index at 2 hours after bypass discontinuing were
      2.2+/-0.04, 3.0+/-0.1 and 2.8+/-0.05 L/m(2) in group 1, 2 and 3, respectively
      (p<0.01). The left ventricular stroke work index were 24.8+/-1.3, 34.5+/-1.6 and
      31.6+/-1.2 g/m x m(2) in group 1, 2, 3, respectively (p<0.01). The release of CK
      MB in group 2 and 3 were lower than in group 1 (68+/-7, 81+/-9 versus 116+/-10
      IU/L, p<0.01). CONCLUSIONS: Terminal warm cardioplegia with controlled aortic
      root reperfusion and ischemic preconditioning equally improve cardiac function
      and reduce the requirement of inotropic agents in patients undergoing valve
      replacement.

PMID- 11292930
TI  - The effect of Celsior solution on 12-hour cardiac preservation in comparison with
      University of Wisconsin solution.
AB  - BACKGROUND: Celsior is a new extracellular-type preservation solution which has
      been developed to act not only as a storage medium but also as a perfusion fluid
      during initial donor heart arrest, poststorage graft reimplantation and early
      reperfusion. We designed this experimental study to evaluate the effect of the
      Celsior solution in comparison with the University of Wisconsin solution from the
      viewpoint of energy depletion. METHODS: Adult mongrel dogs weighing 9 to 13 kg
      were divided into two groups. In the UW group (n=7), a 4 degrees C University of
      Wisconsin solution was used for coronary vascular washout and storage following
      cardiac arrest using a glucose-insulin-potassium solution. In the Celsior group
      (n=7), the Celsior solution was used to obtain cardiac arrest, coronary vascular
      washout and storage. High energy phosphate levels and myocardial pH were measured
      using (31)P-nuclear magnetic resonance spectroscopy immediately after
      preservation and at 3, 6 and 12 hours after preservation. After 12-hour cold
      storage, left ventricular free wall tissues were harvested for histological
      examination. RESULTS: High energy phosphate levels and myocardial pH were
      significantly better preserved in the Celsior group than in the UW group. In the
      histological findings, glycogen granules were preserved well in the Celsior
      group. CONCLUSIONS: We conclude from our study that the Celsior solution is
      comparable to the University of Wisconsin solution for use in 12-hour heart
      preservation in canine models.

PMID- 11292932
TI  - Aortopulmonary window coexisting with tetralogy of Fallot.
AB  - Aortopulmonary window is a rare cardiac malformation presenting either in the
      isolated form, or in association with other cardiac anomalies. The isolated form
      usually presents an increased pulmonary blood flow as the main clinical feature,
      but if associated with other cardiac anomalies the clinical findings change
      according to the additional defect. Only 19 cases of aortopulmonary window
      associated with tetralogy of Fallot have been reported. Five of them have
      associated pulmonary atresia. We report two neonatal cases of aortopulmonary
      window and tetralogy of Fallot, one of them presenting an associated pulmonary
      atresia.

PMID- 11292933
TI  - Corrected transposition of the great arteries diagnosed in an 84-year-old woman.
AB  - Corrected transposition of the great arteries without associated cardiac
      anomalies is a rare cardiac malformation. Few patients with this anomaly survive
      beyond 50 years of age because of systemic ventricular dysfunction or development
      of AV valvular regurgitation or conduction disturbance. We describe an autopsied,
      uncomplicated corrected transposition of the great arteries case in which the
      patient died at 84 years of age. We believe this patient to be the longest
      surviving corrected transposition of the great arteries associated person in the
      world.

PMID- 11292935
TI  - Possible intra-aortic balloon pump "function-related" mechanism of embolic events
      in patient with protruding atheroma in the thoracic aorta.
AB  - A possible new functional mechanism of atheromatous embolus is presented
      resulting from reversed aortic blood flow during diastolic augmentation by
      balloon counterpulsation. This mechanism is different from mechanical disruption
      during insertion. Despite this, intra-aortic balloon remains an important asset
      in the management of hemodynamically challenged patients.

PMID- 11292934
TI  - Repair of aortic root abscess cavity with Gelatin-Resorcin-Formol biological
      glue.
AB  - We report a case of infective endocarditis in which Gelatin-Resorcin-Formol
      biological glue enabled safe and effective aortic root repair to be performed in
      a 57-year-old man with infective endocarditis and subsequent aortic valve
      insufficiency.

PMID- 11292936
TI  - Left ventricular thrombosis after blunt chest trauma.
AB  - A 22-year-old man was admitted to our observation with left ventricular thrombus
      arising after blunt chest trauma occurring during a ski accident one year before.
      None was obtained from a review of instrumental and laboratory data at trauma
      time. Transesophageal echocardiography showed an intraventricular thrombus and
      severe hypokinesia at the apex. Standard cardiac surgery procedure was performed
      and postoperative period was uneventful. Echocardiography controls at 6/12 months
      showed a normal apex kinesia. This case shows the importance of hospitalization,
      hemodynamics monitorization and late serial echocardiographic controls for timely
      diagnosis and management of myocardial contusion and consecutive ventricular
      thrombus formation to prevent life-threatening complications.

PMID- 11292937
TI  - Comparison of internal cardioverter defibrillator implantation techniques:
      subpectoral position.
AB  - BACKGROUND: To compare surgical techniques for subpectoral implantation of
      internal cardioverter defibrillator (ICD). METHODS: Sequential comparison with
      review of the literature. SETTING: University Hospital. PARTICIPANTS: the
      patients requiring ICD. INTERVENTIONS: ICD insertions and device testing.
      MEASUREMENTS: defibrillation and pacing thresholds, defibrillator lead impedance,
      operative time, and proximity of generator site to midline, clinical outcomes.
      RESULTS: Comparable efficacy in defibrillation, surgical time and medial
      placement. No wound infections, seromas or lead dislodgments. Preservation of
      pectoral muscle integrity. CONCLUSIONS: Lateral single incision subpectoral ICD
      generator placement can be applied consistently with good RESULTS.

PMID- 11292938
TI  - Anchoring the Duran flexible annuloplasty ring with continuous sutures.
AB  - We practised a deviced method of anchoring the Duran flexible ring with
      continuous sutures. After passing through 3/0 monofilament sutures at the right
      and left fibrous trigones, both sutures are passed through the ring between the
      corresponding ring marker and continuous sutures are placed to attach the ring to
      the mitral valve annulus. This technique requires less time to anchor the ring
      than the original method with interrupted sutures and can prevent narrowing the
      mitral valve annulus following the deformity of the flexible ring. This technique
      can contribute to extend the indication of the prosthetic ring in mitral valve
      surgery.

PMID- 11292939
TI  - Infrainguinal arterial reconstruction with autologous vein grafts: are the
      results for the in situ technique better than those of non-reversed bypass? A
      long-term follow-up study.
AB  - BACKGROUND: The aim of this study was to answer the question if the in situ
      technique in infrainguinal arterial reconstruction is better than the non
      reversed one in long-term follow-up. METHODS: Patients were included in a
      prospective study at operation. 387 infrainguinal arterial reconstructions in 367
      patients performed from 10-88 to 12-98 were retrospectively analysed. RESULTS:
      280 non-reversed and 107 in situ bypass procedures were performed. Primary
      patency rates at 60 months were 63.3% for non-reversed and 57.9% for in situ
      grafts (p=n.s.). Primary assisted patency rates were 81.8% and 84.5% respectively
      (p=n.s.). Limb salvage rate was not different in either group. The 30-day
      mortality was 1.9% in the in situ group and 0.7% in the non-reversed group
      (p=n.s.). CONCLUSIONS: There is no difference in outcome between in situ and non
      reversed vein grafting. Absence of statistical difference between the two
      procedures may be mainly due to the routine use of angioscopic quality control.

PMID- 11292941
TI  - Outpatient management of superficial temporal artery aneurysms.
AB  - BACKGROUND: To evaluate the feasibility and safety of surgical treatment of the
      superficial temporal artery aneurysms on an outpatient basis. METHODS: The
      records of 5 patients seen at our institution from 1983 to 1997 were reviewed
      retrospectively. Preoperative diagnosis was made by patient s history and
      physical examination, with no further evaluation. RESULTS: Outpatient ligation
      and excision of four aneurysms of distal branches of the superficial temporal
      artery (3 frontal, 1 parietal) and one involving its proximal portion was
      performed under local anesthesia. Supplementation with minimal intravenous
      sedation facilitated the treatment in an uncooperative child and in the patient
      affected with proximal STA aneurysm. All procedures were uneventful. Patients
      were discharged a few hours after surgical treatment. No patient required
      hospitalization following discharge. No recurrence was noted during follow-up
      periods of 2 to 16 years. CONCLUSIONS: Outpatient diagnosis and excision of
      aneurysm of the superficial temporal artery can be performed safely. Significant
      advantages of this pathway include no hospital admission and cost reduction.

PMID- 11292940
TI  - Influence of low proximal aortic pressure on spinal cord oxygenation in
      experimental thoracic aortic occlusion.
AB  - BACKGROUND: To evaluate the effect of low proximal aortic pressure on
      cerebrospinal fluid (CSF) oxygenation in an experimental thoracic occlusion
      model. METHODS: In nine pigs, continuous intrathecal pO(2), pCO(2) and pH
      monitoring was used during double descending thoracic aortic clamping following
      insertion of an aorto-aortic shunt. In five pigs, the shunt was connected to a
      citrated bag adjusted at approximately 40-45 cm above the heart for partial
      exsanguination in order to decrease mean proximal aortic pressure (MPAP) to below
      50 mmHg. In four animals, sodium nitroprusside infusion was used for this
      purpose. RESULTS: Intrathecal pO(2) demonstrated a significant decrease from
      4.9+/-2.1 to 2.9+/-2.4 kPa after 10 minutes of aortic cross-clamping. Lowering
      proximal aortic pressure caused a further significant decrease to 1.2+/-1.7 kPa
      (p<0.05). In seven pigs (5 in the exsanguination and 2 in the vasodilator group),
      restoration of mean proximal aortic pressure to 94.0+/-27.7 caused a recovery of
      CSF pO(2) from 1.2+/-1.9 to 2.8+/-3.0 (p<0.05). CONCLUSIONS: The results of this
      study demonstrate that MPAP which provides spinal cord perfusion through
      subclavian-vertebral arteries are crucial for maintenance of spinal cord
      oxygenation during thoracic aortic occlusion in this pig model.

PMID- 11292942
TI  - Ruptured mycotic aneurysm of the popliteal artery. A case report and review of
      the literature.
AB  - We report a case of a ruptured mycotic popliteal artery aneurysm as a consequence
      of septic embolization from infective endocarditis. The clinical presentation and
      radiological findings are presented. The popliteal, tibio-peroneal, and the
      antero-tibial arteries were reconstructed using an in situ bifurcated saphenous
      vein graft. Follow-up at 24 months disclosed a patent repair with normal ankle
      brachial index.

PMID- 11292943
TI  - Pseudo-aneurysm of the popliteal artery by femoral exostosis in a young child.
AB  - Exostosis is a solitary benign bone tumor frequently observed in children. It may
      be totally quiescent or provoke complications. We report a case of pseudo
      aneurysm of the popliteal artery caused by an exostosis on the lower metaphysis
      of the femur in a 12-year-old boy. This unusual complication mostly reported in
      young males (mean age 19 years) occurs in the context of an initial trauma in
      half the cases. Surgical treatment is a semi-emergency requiring both bone and
      arterial repair. Preventive surgery should be discussed for all cases of
      exostosis with a risk of arterial damage due to the gravity of the potential
      vascular complications.

PMID- 11292944
TI  - Consumption coagulopathy associated with aneurysms of the abdominal aorta and the
      bilateral femoral arteries. Report of a case.
AB  - The authors report a case of a 70-year-old man, with repeating episodes of
      systemic subdermal hematoma due to consumption coagulopathy associated with
      abdominal aortic aneurysm and the bilateral femoral arterial aneurysms. Prior to
      the first operation for abdominal aortic repair, anticoagulation therapy was
      applied to treat thrombocytopenia and hypofibrinogenemia. Five years following
      the first surgery, the same treatment was required before resection of the
      femoral lesions. Consumption coagulopathy is seen in approximately 1-4%
      population of aortic aneurysms, however, repeated appearance of symptomatic
      coagulopathy is rarely reported. Anticoagulation therapy was effective to
      normalize the coagulation and fibrinolytic system and followed by uneventful
      surgical resection of the aneurysms.

PMID- 11292945
TI  - Left-sided inferior vena cava in patients submitted to aorto iliac surgery. Our
      experience and review of the literature.
AB  - We present two cases of left sided inferior vena cava, one unexpectedly observed
      during an operation of aorto bifemoral bypass in a patient with severe Leriche
      syndrome and almost complete obstruction of the infrarenal aorta, the second in a
      patient with an aneurysm of the abdominal aorta, in whom the anomaly was
      recognized before the operation. This very rare congenital malformation (0.2
      0.5%) was not recognized in the first patient by the duplex scanner performed
      preoperatively, probably because of the low level of suspicion carried on by an
      experienced operator. Computer tomography angiography or magnetic resonance
      angiography, which would have surely shown us the anomaly, were not done in the
      first patient because, in the lack of an aneurysmal disease or other abdominal
      pathological situations, these investigations were not required before operation.
      The possible hazards of such an unrecognized malformation are great, mostly in
      terms of uncontrollable intraoperative hemorrhages, but the final outcome of this
      case was positive.

PMID- 11292946
TI  - Surgical management of acquired non-malignant tracheo-esophageal fistulas.
AB  - BACKGROUND: The aim of this study was to evaluate the results of one-stage
      surgical management of acquired non-malignant tracheo-esophageal fistulas (TEF).
      METHODS: Six consecutive patients, 2 men and 4 women with median age of 65 (range
      34-71) years had tracheo-esophageal fistulas resulting from a median of 33 (range
      20-86) days of intubation via oro-tracheal or tracheostomy tubes. Median TEF
      length was 2.6 (range 1.8-3.5) cm and the defect was associated with a tracheal
      stenosis near or immediately below the stoma in 4 cases (66%). Tracheal resection
      and anastomosis with primary esophageal closure was carried out in 4 patients;
      direct closure of the tracheal and esophageal defects with muscle flap
      interposition was performed in 2 patients: tracheal stoma was left in site
      because of the high risk of postoperative respiratory insufficiency related to
      chronic obstructive pulmonary disease. RESULTS: All six patients had complete
      control of the TEF. One perioperative death occurred on day 27 (16%) related to
      the recurrence of endocranial bleeding. The 5 long-term survivors were routinely
      submitted to tracheo-bronchoscopic control and only one (20%) revealed
      granulation tissue at the suture line requiring two consecutive bronchoscopic
      removals. CONCLUSIONS: Postintubation tracheoesophageal fistula is usually best
      treated with one-stage surgical procedure: which preferably consists of tracheal
      resection and anastomosis and primary esophageal closure.

PMID- 11292947
TI  - Traumatic rupture of the bronchus.
AB  - We experienced a case of incomplete traumatic rupture of the bronchus which was
      operated on two months after a traffic accident. Traumatic rupture of the
      bronchus is rare after blunt chest injury but it can have serious consequences.
      Early surgical repair is recommended without repeated attempts to remove
      granulation tissue if the initial attempt at non-surgical repair results in
      failure, even in the case of incomplete rupture.

PMID- 11292948
TI  - Surgical management of solitary pulmonary nodules. An unexpected lucky case.
AB  - The case of a 63-year-old woman with a solitary pulmonary nodule (SPN) is
      reported. Surgical wedge resection revealed an hamartoma. Digital examination of
      the lung parenchyma showed an unexpected (not previously visualized by thoracic
      imaging) second nodule that intraoperative frozen examination revealed an
      adenocarcinoma. The operation was completed with a right upper lobectomy and
      complete lymphoadenectomy. The authors recommend an early open surgical procedure
      for any SPNs with risk factors for developing lung cancer.

PMID- 11292949
TI  - Atypically located pericardial cysts.
AB  - Pericardial cysts are generally recognized when they present in a cardiophrenic
      angle, but may not be suspected when they occur elsewhere in the thorax. To
      highlight the unusual localisations of pericardial cysts, we represent two
      patients with cysts of which one was adjacent to the left pulmonary hilum and the
      other was located in the subpulmonary region. The clinicians should take into
      consideration this entity in the differential diagnosis of cystic lesions of the
      mediastinum.

PMID- 11292950
TI  - Redo coronary artery bypass grafting for graft disease in asymptomatic dialysis
      patients.

PMID- 11292951
TI  - An unusual popliteal entrapment in a patient with rheumatoid knee.

PMID- 11292952
TI  - Cardiovascular repercussion of irresectable giant mediastinal schwannoma.

PMID- 11292953
TI  - Congestive heart failure in hypertensive patients with normal systolic function
      and dynamic left ventricular outflow obstruction.
AB  - BACKGROUND: Hypertensive patients with left ventricular hypertrophy and normal
      systolic function can develop congestive heart failure refractory to conventional
      drug therapy with digoxin, diuretic, and vasodilators. METHODS: We studied 8
      patients with a history of systemic hypertension (6 females and 2 males, mean age
      69+/-6 years), affected by New York Heart Association (NYHA) class IV congestive
      heart failure notwithstanding conventional drug therapy with digoxin, diuretic,
      and vasodilators. After clinical history and physical examination, blood
      chemistry including cardiac enzymes, arterial blood gases, chest roentgenogram,
      standard 12-lead ECG, and complete echocardiographic study were performed in all
      patients. RESULTS: In all cases, a left ventricle with increased wall thickness,
      normal cavity size, and normal or supernormal systolic function was shown. All
      patients had left ventricular systolic dynamic obstruction, with peak gradient
      between 36 and 130 mmHg (mean 83+/-31). After having stopped treatment with
      nitrates, digoxin, and diuretics, drug therapy with calcium channel antagonists
      or beta-blockers was started, and rapid clinical improvement with disappearance
      of left ventricular outflow obstruction was observed. CONCLUSIONS: Sometimes, a
      distinction between several forms of heart failure is clinically impossible.
      However, when conventional therapy is not effective in patients with longstanding
      history of systemic hypertension and ECG signs of left ventricular hypertrophy,
      diastolic heart failure and/or dynamic left ventricular obstruction should be
      suspected. Thus, an early echocardiographic study should be performed.

PMID- 11292954
TI  - [Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing
      process of lower limb ulcers. An open multicentre study, controlled and
      randomized].
AB  - OBJECTIVE: To determine the increase in healing rate of venous ulcer in patients
      receiving a micronised purified flavonoid fraction (MPFF) as supplementation to
      standard local care. METHODS:  DESIGN: A randomised, open, controlled,
      multicentre study. SETTING: Departments of Dermatology and University Outpatients
      Clinics. PATIENTS: One hundred and forty patients with chronic venous
      insufficiency and venous ulcers. INTERVENTION: PATIENTS received standard
      compressive therapy plus external treatment alone or 2 tablets of MPFF daily in
      addition to the above treatment for 24 weeks. MAIN OUTCOME MEASURE: Healing of
      ulcers and their reduction in size after 24 weeks of treatment. RESULTS: The
      percentage of patients whose ulcers healed completely was found to be markedly
      higher in those receiving MPFF in addition to standard external and compressive
      treatment than in those treated with conventional therapy alone (46.5% vs 27.5%;
      p<0.05. OR=2.3, 95% CI 1.1-4.6). Ulcers with diameters <3 cm were cured in 71% of
      patients in the MPFF group and in 50% of patients in the control group, whereas
      ulcers between 3 and 6 cm in diameter were cured in 60% and 32% of patients
      (p<0.05), respectively. The mean reduction in ulcer size was also found to be
      greater in patients treated with MPFF (80%) than in the control group (65%)
      (p<0.05). The cost-effectiveness ratio (cost per healed ulcer) in the MPFF group
      was 1026.2 compared with 1871.8 in the control group. CONCLUSIONS: These results
      indicate that MPFF significantly improves the cure rate in patients with chronic
      venous insufficiency.

PMID- 11292955
TI  - [Functional assessment of mitral stenosis].
AB  - The following parameters must be taken into account when assessing the severity
      of mitral stenosis: symptoms, objective examination, electrocardiogram, chest X
      ray, a simple exercise test with or without cardiopulmonary test,
      echocardiography and lastly a hemodynamic test. Differences are often observed
      between the clinical and instrumental findings. In these cases a major
      contribution is made by the use of physical effort in response to both ECG and
      heart catheterization in order to quantify the patient's functional deficiency
      and valve response. The latter aspect must be validated using a simultaneous
      comparison between echocardiography and the hemodynamic test and longitudinal
      clinical studies.

PMID- 11292956
TI  - Systemic sclerosis (scleroderma). A case of recovery of cardiomyopathy after
      vitamin E treatment.
AB  - A 60-year-old woman with systemic sclerosis, systemic hypertension, and chronic
      renal failure, presented with clinical manifestations of heart failure. An
      echocardiogram showed a mildly dilated left ventricle and global hypokinesis. A
      six-month treatment including reduced sodium intake, furosemide, and nifedipine
      did not change the clinical and instrumental findings. Casually, vitamin E (600
      mg daily) was added. After 6 months, clinical manifestations of heart failure
      were disappeared and the echocardiogram showed a normally-sized left ventricle
      with normal wall motion.

PMID- 11292957
TI  - [Acute myocardial infarction complicated by ventricular aneurysm during
      pregnancy. A clinical case and review of the literature].
AB  - Acute myocardial infarction is an uncommon complication in pregnant women. The
      case of a 30-years-old patient who suffered of an acute myocardial infarction
      during the first trimester of pregnancy, with secondary development of left
      ventricular aneurysm is presented. She had a sudden death 3 months after
      delivery, while waiting for coronary arteriography.

PMID- 11292958
TI  - [Retroperitoneal fibrosis associated with neuritis symptomatology due to external
      iliac artery stent subadventitial migration].
AB  - The occurrence of a neuritis of the ischiatic nerve and the genito-femoral nerve
      due to the implant of three stents in the iliac artery, is an extremely rare
      complication, especially if associated with retroperitoneal fibrosis which caused
      a nevritis symptomatology. A case of stent migration in the subadventitial space
      which caused 4 years from angioplasty and stents implant, a nevritis
      symptomatology. Retroperitoneal fibrosis has been considered as a consequence of
      the stents presence and of their chronic irritational activity, especially for
      what concerns the stent migrated in the subadventitial space; the procedure
      personally performed in this case is reported.

PMID- 11292959
TI  - [Anomalies of the inferior vena cava in patients treated with surgical vascular
      procedures in the aorto iliac area. Report of 2 cases and review of the
      literature].
AB  - Two cases of left-sided inferior vena cava observed in a patient affected by
      Leriche syndrome and the other affected by aortic abdominal aneurysm (AAA) are
      presented. This very rare congenital malformation (0.2-0.5) was not recognized by
      the duplex scanner performed preoperatively probably because of the low level of
      suspicion carried on by an experienced operator. Angio-CT e angio-MR which would
      have surely showed the anomaly, were not done because in the absence of an
      aneurysmal disease or other abdominal situations, these investigations were not
      required before operation. An angio-CT was performed routinely to the patient
      affected by AAA and so the left-sided vena cava was observed before operation;
      and then an abdominal arteriography and an ilio-caval venography were required
      which documented the vena cava anomaly. Surgical interventions didn t have
      complications. In the case of Leriche syndrome an aorto-bifemoral bypass was
      performed, and in the case of abdominal AAA an aortic left-iliac right-femoral
      bypass. Preoperative unrecognizing of this venous malformation is very hazardous
      mostly in terms of uncontrollable intraoperative hemorrhages. Ultrasonographic
      diagnosis with duplex scanner has to be very accurate in order to observe not
      only arterial diseases but also the possible venous anomalies of the abdominal
      district.

PMID- 11292960
TI  - Acute lower limb thrombosis caused by a congenital fibrous ring of the
      superficial femoral artery.
AB  - Segmentary isolated stenosis or obstructions of the superficial femoral artery in
      young people are rarely reported. In patients, most of them women, affected by
      chronic symptomatology of the lower limbs, the aetiology has been referred to
      fibromuscular dysplasia with unusual localization. We report a case of acute
      lower limb thrombosis in a young woman caused by a congenital fibrous ring of the
      superficial femoral artery and the treatment we performed in this situation
      including the complication that happened after the percutaneous transluminal
      angioplasty that we carried out in order to reduce the stenosis of the femoral
      superficial artery. Histological examination of the lesion demonstrated the
      nature of the fibrous ring caused by an embryological anomaly, followed by a
      secondary thrombosis in a woman not using oral contraceptives and without any
      alteration of the coagulation chain. Fibromuscular dysplasia of the femoral
      artery is commonly caused by previous thigh injuries, thromboembolic events with
      recanalization of the artery or arteritis, but in some cases appears to be the
      consequence of primitive intimal dysplasia. When a fibromuscular dysplasia is
      suspected, all authors agree on the necessity for a screening of the two
      preferential localizations of the disease: common carotid artery and renal
      artery, in the case reported the result was negative.

PMID- 11292961
TI  - [Aneurysms of the common trunk, anterior descending and right coronary artery in
      a 33 years old man with acute myocardial infarction. A case report].
AB  - Coronary artery aneurysms are often incidental findings during coronary
      angiography; they are mostly secondary to atherosclerosis or vasculitis, they are
      rarely congenital. Right coronary circumflex and anterior descending arteries are
      usually involved but only few cases of aneurysms of left main coronary artery are
      reported. A case of coronary artery aneurysms is described involving left main,
      right and anterior descending coronary arteries, probably secondary to atypical
      Kawasaki disease in a 33 years old man with acute myocardial infarction.

PMID- 11292962
TI  - [Effectiveness of the combination of alpha tocopherol, rutin, melilotus, and
      centella asiatica in the treatment of patients with chronic venous
      insufficiency].
AB  - BACKGROUND: The aim of this comparative clinical study was to evaluate the
      efficacy of the association of alphatocopherol, rutin, melilotus officinalis, and
      centella asiatica with oral administration in patients with chronic venous
      insufficiency. METHODS: Thirty patients with chronic venous insufficiency have
      been randomized in two groups of fifteen subjects (control and treatment group).
      During the period of treatment the patients didn't wear elastocompressive
      stockings. The therapeutic efficacy and the clinical tolerability of this
      association have been valued with clinical-instrumental evaluations and by a
      control after 15 and 30 days. Functional bothers, cramps and the edema have been
      valued in function presence and of their gravity with a clinical-score between 0
      and 4. RESULTS: At the end of the observation period, a significant improvement
      of the clinical simptomatology was obtained, characterised by a diminution of the
      sovrafascial edema. CONCLUSIONS: The present study confirms previous clinical
      experiences regarding the described treatment and suggests its application in
      chronic venous insufficiency.

PMID- 11292963
TI  - Discussion.

PMID- 11292964
TI  - Discussion.

PMID- 11292965
TI  - Discussion.

PMID- 11292966
TI  - Discussion.

PMID- 11292967
TI  - Discussion.

PMID- 11292968
TI  - [Gene therapy is probably going to fulfil expectations. Not yet a risk-free
      therapeutic method].

PMID- 11292969
TI  - [Psychiatry and ADHD/DAMP. Unclear and out-of-date terminology still results in
      misunderstanding].

PMID- 11292970
TI  - [No connection between the number of amalgam fillings and health. Epidemiological
      observations from a population study of women in Gothenburg].
AB  - Number of dental amalgam fillings and baseline serum mercury concentration were
      assessed with respect to a number of health related variables as part of a
      population study of women. There was no increased incidence of symptoms, no
      derangement of laboratory variables of clinical significance, nor any increased
      mortality or increased risk of myocardial infarction, stroke, diabetes or cancer
      in women with many amalgam fillings compared with those with few fillings, nor in
      women with higher serum mercury concentration compared with those with lower
      serum mercury concentration.

PMID- 11292971
TI  - [Debriefing after operative childbirth didn't reduce depression].

PMID- 11292972
TI  - [Postprandial hyperglycemia. Cardiovascular risks and new therapeutic
      strategies].
AB  - In contrast to fasting glucose, postprandial hyperglycemia in type 2-diabetes has
      been a relatively neglected area. However, postprandial glucose spikes contribute
      significantly to overall glycemic control and are strongly correlated with
      cardiovascular morbidity and mortality (as opposed to fasting glucose). Here we
      review extant data implicating postprandial hyperglycemia as a tangible target
      for novel antidiabetic drugs with improved potential to curb not only deleterious
      glucose excursions, but also the macrovascular complications associated with
      them.

PMID- 11292973
TI  - [Unsatisfactory pain treatment in attacks of acute intermittent porphyria.
      Vasodilation an alternative if the pain is shown to be the pain of intestinal
      angina].
AB  - Abdominal pain is by far the most serious symptom in attacks of acute
      intermittent porphyria (AIP). Its cause is unknown. This case suggests visceral
      ischemia as a possible cause of the abdominal pain. A 31-year-old woman with
      recurrent bouts died during an attack; the autopsy revealed a 20 cm necrotic
      gangrene in the ileum. A protracted intestinal vasospasm could have been the
      immediate cause of death. The question as to whether intestinal angina could be
      the cause of abdominal pain in acute intermittent porphyria is discussed.

PMID- 11292974
TI  - [Urinary incontinence a public disease among the elderly--affects both women and
      men].
AB  - Urinary incontinence is a common condition encountered by clinicians in many
      different disciplines. It is a symptom with widespread human and social
      implications, causing discomfort, shame and loss of self-confidence. In the
      elderly, urinary incontinence may be an important factor in the decision to
      institutionalize a person. The prevalence of urinary incontinence increases with
      advancing age in both men and women. Reasons for this are probably
      multifactorial, and may be due to one or more factors in the individual patient.
      Many elderly persons suffering from urinary incontinence do not wish to or are
      incapable of undergoing elaborate workup and treatment. It is important to
      individualize both workup and treatment of the elderly.

PMID- 11292975
TI  - [New drugs require nw follow-up surveillance].
AB  - The marketing of new drugs has been sped up considerably, partly as a consequence
      of the common EU regulatory system. At the time of approval the documentation
      concerning long-term effects and health economic outcomes of a new drug is
      scanty. This is of particular relevance to chronic and debilitating diseases like
      rheumatoid arthritis. In the field of rheumatology new, expensive, and clinically
      effective drugs have been marketed recently. This has lead to subsequent problems
      in the setting of priorities at the clinical as well as the administrative level.
      The demand for appropriate systems for following up of effects, toxicity and
      economy of these drugs has compelled the Swedish Society for Rheumatology and the
      Medical Products Agency to establish a surveillance system for TNF-blockers. This
      was implemented already in the pre-marketing phase, and is presently being
      continued as an observational study after approval. Experience from the
      development phase of this system and some preliminary results are presented.

PMID- 11292976
TI  - [Inadequate management of unnatural deaths].
AB  - A death certificate was issued without a medicolegal autopsy in one third of all
      Swedish cases of unnatural death during 1991 through 1996. Out of 415 unnatural
      deaths in the northern part of Sweden, not subjected to a medicolegal autopsy but
      analyzed in this study, only 14% were reported to police authorities. Elderly,
      women and patients dying after a longer period of hospital care were more often
      not reported to the police. It is recommended that forensic pathologists be
      consulted in order to achieve better management of unnatural deaths.

PMID- 11292977
TI  - [Aneurysm of the iliac artery--an "orthopedic" differential diagnosis].

PMID- 11292978
TI  - [It's a myth that a higher percentage of female physicians result in lower status
      of the profession and lower salaries].

PMID- 11292979
TI  - [The SBU report "Back pain, neck pain" critically illuminated].

PMID- 11292980
TI  - [The benefit of attempts to diagnose myofascial syndrome has not been documented
      anywhere].

PMID- 11292981
TI  - [Complementary questions on prion diseases].

PMID- 11292982
TI  - [Sheep, cattle--and slaughtering?].

PMID- 11292983
TI  - [A dialogue for a consistent view on the "main diagnosis"].

PMID- 11292984
TI  - [Use "positive special treatment" instead of "correction for negative special
      treatment"!].

PMID- 11292985
TI  - [Wrong to stop solo practices].

PMID- 11292986
TI  - [Bitter discussions on diagnoses--nothing new].

PMID- 11292988
TI  - Legislation and regulations regarding the practice of assisted reproduction in
      India.

PMID- 11292987
TI  - Do fertile and infertile people think differently about ovum donation?

PMID- 11292989
TI  - Cook versus Edwards-Wallace: are there differences in flexible catheters?

PMID- 11292990
TI  - Extending the coincubation time of gametes improves in vitro fertilization.

PMID- 11292991
TI  - Soluble CD44 in human ovarian follicular fluid.
AB  - PURPOSE: In the present study, we investigated the existence of soluble CD44
      (sCD44) in human follicular fluid, the relationship between the concentration of
      sCD44 and that of other hormonal parameters, and the prognostic value of sCD44 in
      follicular fluid in in vitro fertilization (IVF) programs. METHODS: A total of 63
      follicular fluid specimens from patients (n = 30) participating in our IVF
      programs was analyzed by RIA and enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The mean concentration (+/- SE) of sCD44 in follicular fluid was 265.4
      +/- 7.8 ng/ml. The variation of the follicular fluid concentration of sCD44 was
      strictly associated with that of human chorionic gonadotropin (hCG) (r = 0.572, P
      < 0.0001). The mean concentration of sCD44 in follicular fluid was significantly
      higher in follicles containing subsequently unfertilized oocytes than that in
      those containing oocytes that had undergone fertilization (P = 0.0428). In the
      analysis of each follicle that contained an oocyte subsequently fertilized, the
      mean concentration of sCD44 was significantly higher in follicular fluid with the
      subsequently good-quality embryos than in that with the subsequently poor-quality
      embryos (P < 0.05). CONCLUSIONS: These results indicated that the concentration
      of sCD44 in follicular fluid reflects the development of embryos derived from the
      same follicle, so the sCD44 in human follicular fluid may be useful in the
      assessment of the prognostic value of IVF programs.

PMID- 11292992
TI  - Superovulation and intrauterine insemination in cases of treated mild pelvic
      disease.
AB  - PURPOSE: Our purpose was to examine the effect of treated mild pelvic disease on
      the outcome of superovulation with intrauterine insemination (SO/IUI). METHODS:
      Three hundred cycles of SO/IUI were retrospectively reviewed for 118 women with
      laparoscopically treated minimal/mild endometriosis and 67 cycles for 28 women
      with minimal/mild distal tubal disease/adnexal adhesions and compared with 265
      cycles in 111 couples with idiopathic infertility. RESULTS: The monthly fecundity
      rate (MFR) of 6.8% and live birth rate (LBR) of 6% in the endometriosis group
      were significantly lower (P = 0.002) than those in the idiopathic infertility
      group (MFR = 13.5%, LBR = 12.1%). The 10.9% MFR and 7.5% LBR in the minimal/mild
      tubal/adnexal disease were not significantly different from those in the other
      two groups. CONCLUSIONS: MFR and LBR were higher after SO/IUI in idiopathic
      infertility compared to those for treated mild/minimal endometriosis or
      mild/minimal tubal/adnexal adhesions. However, SO/IUI still remains a reasonable
      option for both these groups prior to IVF-ET.

PMID- 11292993
TI  - Pregnancy and birth after GnRH agonist treatment for induction of final oocyte
      maturation in a woman undergoing ovarian stimulation for ICSI, using a GnRH
      antagonist (Orgalutran/Antagon) to prevent a premature LH surge: a case report.

PMID- 11292994
TI  - Emergency sperm extraction for transient erectile dysfunction prior to assisted
      conception.
AB  - PURPOSE: During assisted conception treatment the male partner is under stress
      and consequently can fail to produce semen sample prior to egg collection.
      Failure to produce spermatozoa at a given time could lead to cancellation of the
      procedure. METHODS: We report the use of emergency percutaneous epididymal sperm
      aspiration (PESA) for temporary erectile dysfunction in a couple undergoing in
      vitro fertilization treatment. In the last 2 years, we saw three men who failed
      to produce a semen sample on the day of their partners' egg collection procedure.
      RESULTS: In the first case the male partner failed to produce semen after egg
      collection and the cycle was canceled. This clinical scenario was likely to recur
      and one of the options was to consider PESA. In the second case the male partner
      was counseled about the availability of PESA but he managed to produce
      spermatozoa at home. The third patient was unable to produce a semen sample
      despite being provided audiovisual support and being allowed to go home. Five
      hours after the egg collection, emergency PESA was performed after appropriate
      counseling. The procedure yielded motile spermatozoa which were used for
      intracytoplasmic sperm injection which resulted in successful fertilization,
      embryo transfer, and pregnancy. CONCLUSIONS: This case emphasizes that surgical
      procedures, such as PESA,TESA, and TESE, are useful alternatives but should be
      the last option to obtain sperm for ART. Other nonsurgical procedures, such as
      audiovisual aids, producing sperm at home, and the use of sildenafil citrate
      (Viagra) must be offered first to men with temporary erectile dysfunction during
      ART treatment.

PMID- 11292996
TI  - The work of the Multiple Births Foundation.

PMID- 11292995
TI  - Chemotactic responsiveness of human spermatozoa to follicular fluid is enhanced
      by capacitation but is impaired in dyspermic semen.
AB  - PURPOSE: Our purpose was to study the chemotactic responsiveness of human
      spermatozoa from normal and pathological semen samples to follicular fluid (FF),
      as well as the effect exerted by capacitation on sperm chemotaxis. METHODS: The
      chemotactic responsiveness of human spermatozoa to FF was tested by an
      accumulation assay chamber in which they were allowed to migrate through a
      microporous membrane and accumulate in a compartment filled with FF or control
      medium. The percentage of cells with hyperactivated motility among migrated sperm
      was objectively assessed by CASA and its relationship to the accumulation rate
      was studied. Single FFs were tested with single normospermic or dyspermic semen
      samples; the same FF was tested with different semen specimens. The influence of
      capacitation onto the chemotactic responsiveness to FF was investigated by
      comparing the accumulation rate of spermatozoa from normal and pathological
      samples after incubation under capacitating conditions for 1 or 6 hr. RESULTS:
      Some FFs ("active" FFs) effectively attracted human spermatozoa from normospermic
      samples up to a dilution factor of 1:500 (v:v) with control medium. A wide range
      of responses was observed when the same FF was tested with different normal semen
      samples. A longer time under capacitating conditions increased both the
      chemotactic responsiveness of normal semen and its ability to undergo the
      acrosome reaction (AR) in response to A23187. Pathological semen had an impaired
      chemotactic responsiveness to "active" FF that was not enhanced by increasing the
      time spent under capacitating conditions. Dyspermic semen was also less
      responsive to A23187, a finding suggesting incomplete capacitation. CONCLUSIONS:
      Chemotactic responsiveness to FF is acquired in parallel to or as part of the
      capacitation process. Dyspermic semen samples have an impaired capacity to
      achieve both capacitation and chemotactic responsiveness to follicular factors.

PMID- 11292997
TI  - Polycystic ovary syndrome. A diagnostic challenge.
AB  - Polycystic ovary syndrome remains a diagnostic challenge because there is no
      single defining test. The clinical presentation must dictate the extent of the
      work-up. The typical PCOS patient has a history of irregular menses and appears
      hirsute. Demonstration of ovulatory dysfunction and hyperandrogenism can also be
      made by appropriate hormonal measurements. An ultrasound showing multiple small
      ovarian follicles can support a diagnosis of PCOS in the patient for whom the
      clinical diagnosis has been made. Other causes of hyperandrogenism and ovulatory
      dysfunction should be excluded.

PMID- 11292998
TI  - Cardiovascular risk in women with polycystic ovary syndrome.
AB  - Compared with normal cycling women of similar age, women with polycystic ovary
      syndrome (PCOS) have an adverse lipid profile and an increased prevalence of Type
      II diabetes and hypertension. These woman also appear to have greater subclinical
      atherosclerotic disease, as demonstrated by greater carotid intimamedia wall
      thickness and higher levels of coronary calcification. Given the high prevalence
      of PCOS in the female population, this condition may potentially account for a
      significant proportion of the atherosclerotic heart disease observed in younger
      women. This article reviews the issues and uncertainties surrounding the PCOS-CHD
      association.

PMID- 11292999
TI  - Polycystic ovary syndrome, androgen excess, and the impact on bone.
AB  - Polycystic ovary syndrome (PCOS) is a unique, natural model for the study of the
      influence of androgen excess on bone mass among women. Both thin and obese women
      develop PCOS, a presentation that allows for the evaluation of the effects of
      life-long obesity, alterations in body composition (central adiposity), and
      related metabolic abnormalities (hyperandrogenemia, hyperinsulinemia) on the
      skeleton. The relatively high prevalence of PCOS and its manifestation early in
      life render this disorder of particular importance in assessing the influence of
      androgens and androgen-estrogen balance on the attainment of maximal bone mass
      and subsequent development of osteoporosis later in life.

PMID- 11293000
TI  - Insulin-lowering drugs in polycystic ovary syndrome.
AB  - The discovery that insulin resistance has a key role in the pathophysiology of
      PCOS has led to a novel and promising form of therapy in the form of the insulin
      sensitizing drugs. Although no extremely large trials using these drugs for this
      indication have been performed, more than 18 trials have specifically examined
      the effects of these drugs on ovulation, hyperandrogenemia, and dysmetabolic
      features in PCOS. Table 1 summarizes the results of previous trials using each of
      the insulin-sensitizing drugs discussed herein. Among the various agents (i.e.,
      thiazolidinediones, [table: see text] metformin, and D-chiro-inositol), metformin
      is the most widely tested. Metformin may have the added benefit of improving at
      least some features of syndrome X, such as hypertension and obesity. All of the
      evidence to date suggests that metformin is a safe drug to administer to women
      who may become pregnant. In contrast, the two thiazolidinediones currently
      available, rosiglitazone and pioglitazone, are category C drugs that have been
      demonstrated to retard fetal development in animal studies. Overall, insulin
      sensitizing therapy presents a promising and unique therapeutic intervention for
      the treatment of PCOS, offering metabolic and gynecologic benefits for women who
      sustain this syndrome.

PMID- 11293001
TI  - Polycystic ovary syndrome and ovulation induction.
AB  - Before initiating treatment to induce ovulation in cases of PCOS, an appropriate
      evaluation of the patient and her partner, based on individual considerations, is
      important to optimize outcome. For obese patients with PCOS, weight-loss measures
      should be pursued before pharmacologic treatment is initiated. For most patients,
      the pharmacologic agent of choice to induce ovulation is clomiphene citrate,
      alone or in combination with a glucocorticoid. Treatment with metformin, alone or
      in combination with clomiphene citrate, may also be beneficial. For patients not
      responsive to clomiphene citrate, injectable gonadotropin treatment is usually
      warranted, although, depending on individual circumstances, laparoscopic ovarian
      drilling may be appropriate.

PMID- 11293002
TI  - Polycystic ovary syndrome, hyperandrogenism, and insulin resistance.
AB  - Results from recent basic and clinical research investigations have greatly
      improved our understanding of insulin resistance in general and insulin
      resistance associated with PCOS in particular. With this understanding has come
      the possibility of using new methods to treat PCOS. This is particularly true
      when discussing the use of insulin-sensitizing drugs. Caution must be exercised
      in using these drugs because of unforeseen acute or remote adverse side effects.
      Postulated relationships among PCOS, hyperandrogenism, and insulin resistance do
      not completely solve the endocrinologic mystery of the patient with PCOS. For
      example, how does the partial destruction of the ovary (e.g., wedge biopsy or
      ovary drilling by laser or cautery), which does not affect insulin resistance,
      result in ovulatory cycles? Why does the administration of excessive exogenous
      insulin in the case of the insulin-dependent diabetic fail to cause
      hyperandrogenism? Certainly, much remains to be learned about the reproductive
      endocrine disturbance we now call PCOS.

PMID- 11293003
TI  - Neuromodulation in polycystic ovary syndrome.
AB  - Although central and peripheral factors have been implicated in the
      neuromodulation of GnRH in PCOS, there are no definitive or conclusive data to
      establish a primary causal role for any one factor. Because increased GnRH pulse
      frequency is at least a contributor to the secretion of excess LH and
      insufficient FSH that are the proximate cause of chronic anovulation in PCOS,
      strategies to slow the GnRH pulse generator are likely to promote ovulation in
      women with PCOS. Several pharmacologic agents, such as dopamine agonists and
      antagonists, have been tried, but the lack of consistent effects in women with
      PCOS limits their clinical utility. Current treatment strategies include the use
      of the combined oral contraceptive pills, antiandrogens or androgen receptor
      blockers, and insulin sensitizers. Oral contraceptive preparations are effective
      in suppressing ovarian hyperandrogenemia, regulating menstrual cycles, and
      reducing the risk of endometrial hyperplasia. Androgen blockade and antiandrogens
      provide symptomatic relief from androgen-induced acne and hirsutism and have been
      reported to restore ovulation in women with PCOS. Whether this effect is mediated
      peripherally or centrally remains to be clarified. The most recent class of
      pharmacologic agents to gain popularity are the "insulin modifiers." With
      increasing evidence that insulin resistance constitutes a key metabolic element,
      it seems logical that improving insulin sensitivity and glucose disposal might
      wholly, or partially, reverse certain features of PCOS, including anovulation. To
      date, insulin modifiers have proved most promising in improving the clinical
      features and promoting fertility, but whether this effect is centrally mediated
      is yet to be elucidated.

PMID- 11293004
TI  - The role of the adrenal cortex in polycystic ovary syndrome.
AB  - Adrenal androgen excess affects approximately 25% of PCOS patients. The exact
      etiology of this excess in PCOS patients is unclear. Some evidence that adrenal
      androgen excess may be a genetic trait. The adrenal androgen response to ACTH is
      highly individualized, and the relative response seems to be constant over time.
      In addition, there is a strong familial component to adrenal androgen levels in
      normal individuals and PCOS patients. It is possible that the tendency to
      overproduce adrenal androgens is an inherited risk factor for the development of
      PCOS. Overall, few hyperandrogenic patients actually have isolated deficiencies
      of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11-hydroxylase. The
      ovarian hormonal secretion in PCOS can affect adrenal androgen secretion and
      metabolism, although this factor accounts for only part of this abnormality. More
      likely, the adrenal androgen excess results from a generalized
      hyperresponsiveness of the adrenal cortex to ACTH, but without an increase in CRH
      or ACTH sensitivity. Although glucocorticoid administration may improve the
      ovulatory function of these patients, the results are modest and cannot be
      predicted by the circulating androgen levels.

PMID- 11293005
TI  - Polycystic ovary syndrome and hyperprolactinemia.
AB  - Analysis of the evidence linking PCOS and hyperprolactinemia suggests that these
      conditions have independent origins. Elevated prolactin serum levels are
      documented in the early studies of patients with polycystic ovaries. However,
      recent investigators using serial serum sampling have excluded transient
      elevations of prolactin and have shown a less frequent association of these
      disorders. Treatment of individuals with both PCOS and hyperprolactinemia is
      distinct from the management of the individual with only one of these conditions.
      Upon evaluating the therapeutic alternatives for dysfunctional uterine bleeding
      and hirsutism in these patients, the effect of exogenous estrogen and
      progesterone on the secretion of prolactin must be considered. The addition of a
      dopamine agonist (e.g., bromocriptine or cabergoline) to a regimen of clomiphene
      citrate must also be considered as ovulation induction options for these women.
      Finally, future discoveries about the relationship between PCOS and
      hyperprolactinemia will require a better understanding of how the hypothalamus
      regulates the pituitary secretion of LH and prolactin.

PMID- 11293006
TI  - Obesity and weight loss in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) and obesity are common and complicated disorders
      that are influenced by genetic and environmental factors. Obesity is a prominent
      feature of PCOS; at least 50% of patients with PCOS are obese. Obesity appears to
      exert an additive, synergistic effect on the manifestations of PCOS,
      independently impacting insulin sensitivity, risk for diabetes, and adverse
      cardiovascular profile. There is evidence for the benefit of weight reduction in
      the management of PCOS in the obese patient. Weight loss remains a primary
      intervention in treatment of this disorder.

PMID- 11293007
TI  - Diabetes prevalence and risk factors in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome is a reproductive disorder with a significant impact on
      fertility. It is secondarily, and perhaps for the individual primarily, a
      disorder with a marked increase risk for diabetes and glucose intolerance.
      Physicians need to be aware that women who have PCOS are at high risk for
      impaired glucose tolerance and type 2 diabetes. In the author's opinion, they
      should be screened for these abnormalities. Minority women with PCOS may have
      higher prevalence rates of glucose intolerance, and further study of minority
      groups is indicated. The author's data indicate that fasting glucose levels are
      inadequate for such screenings. Fasting glucose levels are relatively poor
      predictors of type 2 diabetes as determined by glucose challenge testing in PCOS.
      These findings may have substantial clinical relevance. They strongly suggest
      that all PCOS women should be screened for glucose intolerance, and that basal
      and 2-hour, glucose-stimulated levels rather than fasting glucose levels alone
      are required for such screening. Further study is necessary to document
      conversion rates to worsening glucose tolerance over time, as well as the
      cardiovascular risk associated with glucose intolerance in PCOS.

PMID- 11293008
TI  - Interorganizational health care systems implementations: an exploratory study of
      early electronic commerce initiatives.
AB  - Changing business practices, customers needs, and market dynamics have driven
      many organizations to implement interorganizational systems (IOSs). IOSs have
      been successfully implemented in the banking, cotton, airline, and consumer-goods
      industries, and recently attention has turned to the health care industry. This
      article describes an exploratory study of health care IOS implementations based
      on the voluntary community health information network (CHIN) model.

PMID- 11293009
TI  - The impact of health insurance plan type on satisfaction with health care.
AB  - Because many previous studies of satisfaction with health care used unreliable
      measures, failed to consider all major health care plan choices, or did not
      include a broad population, this study used a reliability-tested multi-item
      instrument on individuals in HMO, PPO, and fee-for-service insurance plans who
      were randomly drawn from a national population. The findings regarding
      satisfaction were that differences existed among the plan members' satisfaction
      on the dimensions of access to care, availability of resources, and financial
      aspects of care.

PMID- 11293010
TI  - The dimensions of service quality for hospitals: development and use of the KQCAH
      scale.
AB  - Using a combination of qualitative and quantitative research methodologies, this
      study identifies the dimensions of hospital service quality, operationalizes the
      dimensions, and develops an instrument to measure patient satisfaction. This
      instrument, the Key Quality Characteristics Assessment for Hospitals (KQCAH)
      scale, was developed using input from 12 hospital administrators, over 100
      hospital employees, and 23 recent patients and family members.

PMID- 11293011
TI  - Factors underlying organizational change in local health care markets, 1982-1995.
AB  - This article examines the association between characteristics of local health
      care market areas in 1982 and the penetration of new organizational forms in
      those markets in 1995. The Northeast and South exhibit less organizational form
      development than the West. Local markets with higher population size and greater
      density of specialty physicians in 1982 are associated with greater proportions
      of the markets being covered by a wide variety of organizational forms in 1995.

PMID- 11293012
TI  - Staff nurse views of their productivity and nonproductivity.
AB  - Could better collaboration and cooperation to improve productivity occur between
      administrators and nurses if we understood nurse views of their productivity?
      Interviews of 30 staff nurses revealed that these nurses evaluated their
      productivity by the quantity and quality of their work. Working hard, finishing
      everything, and providing excellent care made them feel productive, while
      anything that interfered with this was a source of feeling nonproductive.

PMID- 11293013
TI  - Provider integration and local market conditions: a contingency theory
      perspective.
AB  - In recent years we have witnessed an expanding array of organizational
      arrangements for providing health care services in the U.S. These arrangements
      integrate previously independent providers at one or more points on the continuum
      of care. The presence of so many of these arrangements raises the question of
      whether certain types are more effective than are others to help providers adapt
      to their environment. This article discusses contingency theory as a conceptual
      lens for guiding empirical studies of the effectiveness of different types of
      arrangements.

PMID- 11293014
TI  - How institutional theory speaks to changes in organizational populations.
AB  - In this issue, Begun and Luke note striking variation in organizational
      arrangements across local health care markets and probe how characteristics of
      those markets affect shifts in organizational populations over time. This article
      contributes to this FORUM by focusing on how institutional theory's emphasis on
      the culturally mediated nature of organizational change speaks to the evolution
      of local market structures over time.

PMID- 11293015
TI  - The logic of transaction cost economics in health care organization theory.
AB  - Health care is, at its core, comprised of complex sequences of transactions among
      patients, providers, and other stakeholders; these transactions occur in markets
      as well as within systems and organizations. Health care transactions serve one
      of two functions: the production of care (i.e., the laying on of hands) or the
      coordination of that care (i.e., scheduling, logistics). Because coordinating
      transactions is integral to care delivery, it is imperative that they are
      executed smoothly and efficiently. Transaction cost economics (TCE) is a
      conceptual framework for analyzing health care transactions and quantifying their
      impact on health care structures (organizational forms), processes, and outcomes.

PMID- 11293016
TI  - Normalization of spatial learning despite brain damage in rats receiving ketamine
      after seizure-induction: evidence for the neuromatrix.
AB  - The concept of the neuromatrix assumes that all behaviours are associated with
      complex spatiotemporal electromagnetic fields within the brain. The same complex
      magnetic field can be supported potentially by different mosaics of neuronal
      associations and result in the same behaviours. In the present study the accuracy
      of long-term and short-term spatial memory for rats that had been treated with
      100 mg/kg of ketamine immediately after the induction of seizures by lithium and
      pilocarpine did not differ from normal rats despite the conspicuous multifocal
      neuronal loss. A 30-min. delay of treatment with ketamine resulted in significant
      memory impairment. Whereas deficits in short-term memory were significantly
      correlated with cell loss within the CA field of the hippocampus, deficits in
      long-term memory were related to cell loss within specific thalamic-amygdaloid
      structures. Implications for the concept of the neuromatrix, if valid, are
      discussed.

PMID- 11293017
TI  - Psychoaffective immaturity in psychiatric disorders.
AB  - This study investigated the prevalence of psychoaffective immaturity and tested
      the hypothesis that it associated with bad prognosis. For 135 psychiatric
      patients meeting criteria for personality, neurotic, affective, substance use, or
      psychotic disorders emotional immaturity was rated using the 1985 diagnostic
      criteria of Doutheau, Dubertret, Moutin, and Barrois. 58 subjects (42.96%, 95%
      Confidence Interval: 34.61-51.31) were classified as immature. Scores of the
      Nonimmature and Immature groups were compared for the Beck Depression Inventory
      and the Professional and Social Functioning Assessment Scale. Scores were,
      respectively, significantly higher and lower in those patients classified as
      Immature than those who were classified Nonimmature. When depression was
      controlled by a covariance analysis, the mean difference on the Professional and
      Social Functioning Assessment Scale remained significant. It appears that
      psychoaffective immaturity is a factor associated with severity of psychiatric
      disorders.

PMID- 11293018
TI  - Effect of inapplicable items in the factor structure of the Spanish version of
      the Ways of Coping Questionnaire.
AB  - The aim of this work was to examine how the presence of inapplicable items might
      change the factor structure of the 1984 Ways of Coping Questionnaire by Lazarus
      and Folkman. The Spanish version of the Ways of Coping Questionnaire was
      administered to 156 subjects with university degrees. The 95 women and 61 men
      whose ages were from 18 and 45 years (M = 27.8, SD = 12.1) were of middle
      socioeconomic status. All were residents of Buenos Aires. To study whether
      relevant items modify the factor structure of the Ways of Coping Questionnaire,
      two factor analyses were carried out, one with items rated as not relevant (Item
      Mean) and the other with the same items rated as not chosen. In both factor
      analyses, principal axes method and oblimin rotation were performed, and five
      factors were considered. Congruence indexes were performed. Analysis showed that
      not choosing an item because it does not coincide with one's behavior or ideas is
      not the same as not selecting that item because it does not apply to the current
      threatening situation. Lack of discrimination between situations when analyzing
      data leads to a distorted interpretation of the way in which the subject actually
      behaves or copes with the situation.

PMID- 11293019
TI  - A model for achievement motives, goal orientations, intrinsic interest, and
      academic achievement.
AB  - This study investigated the effects of approach and avoidance achievement motives
      (the motive to achieve success and the motive to avoid failure) on three goal
      orientations (mastery, performance-approach, performance-avoidance goals) and the
      effects of goal orientations on intrinsic interest in learning and academic
      achievement for 157 tenth and 135 eleventh grade students of a Japanese girls'
      high school. Structural equation modeling indicated that mastery goals arose
      mainly from the motive to achieve success; however, the positive relation between
      the motive to avoid failure and mastery goals was also found. Performance
      approach goals were related both the motive to achieve success and the motive to
      avoid failure. Performance-avoidance goals arouse mainly from the motive to avoid
      failure; however, the positive relation between the motive to achieve success and
      these goals was found. Mastery goals positively correlated with intrinsic
      interest and academic achievement, and scores on both performance-approach goals
      and performance-avoidance goals had no significant effects on either intrinsic or
      academic achievement.

PMID- 11293020
TI  - The academic elite in marketing: linkages among top-ranked graduate programs.
AB  - The 10 top-ranked graduate programs in marketing, based on a national survey of
      deans and top administrators, were linked to one another by these programs hiring
      one another's graduates. Approximately one-half of the faculty members in these
      10 programs had graduated from one of these same 10 programs. It is suggested
      that this linkage helps these programs to maintain and enhance their prestige.

PMID- 11293021
TI  - Cognitive processes in panic disorder: an extension of current models.
AB  - Beck and Clark's 1997 information processing model of panic was presented and
      evaluated. In general, studies using the Stroop task have shown panic patients
      have a cognitive bias toward negative and personally relevant information.
      Several studies have also shown that panic patients tend to have more
      catastrophic thoughts and are more likely to misinterpret bodily sensations.
      Further, cognitive-behavioral therapy is more effective than drug therapies. The
      limitations of the cognitive model and cognitive-behavioral therapy were
      discussed, and an extension of current models was proposed. The extension of
      current models combines cognitive-behavioral and psychodynamic concepts and
      techniques and suggests that exposure in vivo used for agoraphobic situations and
      interoceptive exposure used for panic should also be applied to the underlying
      themes of panic disorder.

PMID- 11293022
TI  - A preliminary study of hormone replacement therapy and psychological mood states
      in perimenopausal women.
AB  - Hormone replacement therapy (HRT) for perimenopausal women has been suggested to
      minimize the physical symptoms of menopause and improve mood and psychological
      functioning; however, the therapy remains controversial. In this study the
      effects of such therapy (comprising tablets, patches, and implants) on mood
      states was investigated within a sample of 70 perimenopausal women who were
      attending a family planning clinic within the Brisbane metropolitan area. On a
      battery of standardized questionnaires, including the General Health
      Questionnaire, the Profile of Mood States, the Eysenck Personality Questionnaire,
      and the Menstrual Distress Questionnaire, those 35 women who were using hormone
      replacement therapy prescribed by the clinic physician reported significantly
      lower scores on anxiety, insomnia, and somatic symptoms than did a comparable
      group of 35 untreated perimenopausal women. These findings provide some tentative
      support for the beneficial effects of the therapy on physical symptoms and
      psychological mood states related to the onset of menopause. Given increased life
      expectancy, there is a growing need for research into issues of aging.

PMID- 11293023
TI  - Integration among psychotherapies and the future of psychotherapy.
AB  - As society as a whole and the scientific world have begun to expect that the
      validity of psychotherapy be verified, a scientific and integrated approach to
      psychotherapy is the only possible answer. The development of operational
      definitions and the use of scientific designs represent the most effective way to
      generate empirical data and the only way to integrate psychotherapy objectively
      into general psychology.

PMID- 11293024
TI  - Stability and correlates of the California Verbal Learning Test for a sample of
      normal elderly persons.
AB  - The test-retest stability of the California Verbal Learning Test was examined for
      a normal elderly sample of 28 men and 74 women along with the correlation for
      total recall with scores on selected variables. Mean age was 72 yr. The test was
      re-administered after one year. Mean total recall did not change; the stability
      coefficient was .64. Coefficients for the other scores ranged considerably (.27
      for recognition hits to .62 for perseverations) and were compared with prior
      research findings. Recall was moderately correlated with scores on the North
      American Reading Test, Trails B, visual reproductions, and subjective memory
      ability.

PMID- 11293025
TI  - Determinants of infants' understanding of supporting relations: amount of contact
      versus position of the center of gravity.
AB  - This study investigated the developmental age at which infants recognize about
      supporting relations between objects and what information they use to judge
      whether a supported object will fall down or not. Four kinds of events were used.
      All events involved support in relation of two boxes, which differed in the
      amount of contact between objects and the amount of discrepancy between the
      supported object's position and its most balanced position. 115 infants (3 to 13
      mo.) saw 4 events which differed on these two variables. Infants 10 months and
      older looked longer at the event in which the center of a supported box was just
      outside of the edge of a supporting box, that is, a support relation in which it
      was difficult to anticipate whether the box would fall down or not. Analysis
      suggested that infants' attention is not determined by only one simple stimulus
      variable but by more complicated variables (such as uncertainty of prediction).

PMID- 11293026
TI  - Lay theories of suicide.
AB  - The rank order of a set of 32 causal attributes for depression was similar to
      that for suicide, as judged by a sample of 66 undergraduates.

PMID- 11293027
TI  - Demographic variables and microCog performance: relationships for VA patients
      under treatment for substance abuse.
AB  - The associations of demographic variables with cognitive performance, as measured
      by the MicroCog ability domain scores, were assessed with 222 substance abusers
      who were patients in a VA medical center. Analysis indicated that age was
      negatively related to all five outcomes scores, and education was positively
      related to measures assessing Attention/Mental Control and Reasoning/Calculation.
      These findings are consistent with past theoretical and applied research. The
      demographic variables, as a group, accounted for a total of 17% to 37% of the
      variance in the five domain scores.

PMID- 11293028
TI  - Relationship of numbing to alexithymia, apathy, and depression.
AB  - The present study assessed the relationship between numbing and three associated
      conditions of alexithymia, apathy, and depression, utilizing data collected on
      353 Vietnam combat veterans diagnosed with Posttraumatic Stress Disorder from in-
      and out-patient settings and an outreach center at various Department of Veterans
      Affairs Medical centers. All subjects completed four self-report measures: the
      Glover Numbing Scale, the Beck Depression Inventory, the Apathy Evaluation Scale,
      and the Toronto Alexithymia Scale-20. The correlation matrix indicated that
      scores on the four measures were moderately to highly correlated. Principal
      components analysis with a varimax rotation indicated a five-factor solution that
      provided evidence for the factorial validity of each of the constructs assessed.
      Results of the factor analysis of items from the four measures were consistent
      with numbing being a separate and distinct construct from alexithymia, apathy,
      and depression. In general, results indicated that all constructs measured were
      separate and distinct from one another.

PMID- 11293029
TI  - Neurotic perfectionism, perceived stress, and self-esteem among Japanese men: a
      prospective study.
AB  - The present study examined the relationship between self-report scores of
      neurotic perfectionism and of perceived stress and self-esteem 6 wk. later among
      146 Japanese male college students. Hierarchical regression analysis indicated
      that scores for neurotic perfectionism accounted for statistically significant
      but functionally small variance (4% and 3%) in scores for perceived stress and
      self-esteem obtained at Time 2 (6 wk. later), after controlling for the scores
      for perceived stress and self-esteem at Time 1, respectively.

PMID- 11293030
TI  - A short-form measure of loneliness among second-generation migrants.
AB  - The purpose of this study was to investigate the psychometric characteristics of
      a 6-item measure to assess loneliness among 109 second-generation adolescent
      migrants. Analysis supported the validity and reliability of the scale with this
      sample of acculturating adolescents.

PMID- 11293031
TI  - Support for the progressively finer attributes theory: two experiments.
AB  - In this paper two experiments support and amplify Coll and Coll's 1994
      Progressively Finer Attributes Theory of Memory Trace Development. Important to
      the current paper are five propositions of this theory. (1) The memory trace
      develops along an attribute dimension from coarse/general to fine/specific
      attributes. (2) Forgetting is a reverse movement from fine to coarse as
      increasingly less fine attributes are lost. (3) A memory trace consists of a
      bundle of defining attributes and relating' attributes. There are no constraints
      on the type of attribute included in the attribute bundle or in the order of
      types acquired. The trace name is defined by the attribute bundle it represents.
      (4) Access to any defining attribute of a memory trace gives full access to all
      other attributes of the trace bundle. (5) In the early phases of trace
      development the attributes are preeminent in recall but, as familiarity with a to
      be-learned item increases, the attributes become increasingly cohesive and the
      name assumes preeminence. As forgetting progresses, there is a return to the
      original state (attributes are preeminent). Exp. 1 supports Propositions 3 and 4
      and Exp. 2 supports Propositions 3 and 5. Both experiments provide validation of
      Propositions 1 and 2 beyond that in prior work. The authors present arguments
      that the coarse-to-fine movement of the Progressively Finer Attributes Theory is
      the mechanism by which Levels of Processing operates.

PMID- 11293032
TI  - Suicide in a northeastern police department.
AB  - A northeastern American municipal police department experienced a cluster of
      suicides in 1987-1993 but experienced none in the period 1994-1999.

PMID- 11293033
TI  - Peer conflict avoidance: associations with loneliness, social anxiety, and social
      avoidance.
AB  - Failure to resolve peer conflict is associated with children's reports of
      loneliness, social anxiety, and social avoidance. Although these relationships
      are well established, researchers have not examined the association between the
      avoidance of peer conflict and various adjustment characteristics. The current
      study examined the association between avoidance of conflict and measures of
      loneliness, social anxiety, and social avoidance for 59 pupils in Grade 4 (31
      boys and 28 girls) and 47 in Grade 8 (22 boys and 25 girls). Volunteers indicated
      that conflict avoidance based on autonomy, e.g., independence issues, and
      interpersonal issues, e.g., closeness and cohesion, was associated with scores on
      loneliness for boys and girls, respectively. Conflict avoidance for emotional and
      physical well-being and fear of punishment was associated with increased reports
      of loneliness and social anxiety for children in Grade 4.

PMID- 11293034
TI  - The Type A/B behaviour pattern in samples of urban and rural men.
AB  - The present study assessed the prevalence of the Type A behaviour pattern in a
      rural and an urban sample of men in Norway. The study was carried through on data
      collected for other purposes, reported earlier in 1998 and 1999, to evaluate
      whether there were differences in Type A behaviour pattern between the two
      environmental settings. The Type A behaviour pattern was assessed in both studies
      using the Jenkins Activity Survey. Analysis of the data on the Global Type A
      scale indicated that, on average, participants in both environments reported as
      Type Bs as opposed to Type As. However, the distribution of scores on the
      subscales of the Jenkins Activity Survey showed that mean scores on the Type A
      behaviour attributes were higher in the urban sample than those in the rural
      sample. The results concerning the expression of the Global Type A from these
      samples supported expectations about differences in challenges of a competitive
      environment such as an urban setting, expressed in the literature.

PMID- 11293035
TI  - Comparison of visual motor development in Hong Kong and the USA assessed on the
      Qualitative Scoring System for the Modified Bender-Gestalt test.
AB  - This study compared the visuomotor development of young children in Hong Kong and
      the USA assessed on the Qualitative Scoring System for the Modified Bender
      Gestalt test. 744 children aged 4:6 to 8:5 years from 6 kindergartens and 6
      primary schools in Hong Kong were administered the Modified Bender-Gestalt test.
      The Qualitative Scoring System was used to measure the children's visuomotor
      development. Their visuomotor scores were then compared with norms for children
      in the USA. Analysis indicated significant differences across all age groups of
      4:6 to 8:5 years in 6-mo. units. Consistent with previous research, children in
      Hong Kong outperformed their western peers. Percentile scores and T scores for
      children in Hong Kong in each age group were reported.

PMID- 11293036
TI  - Relation between humor and empathic concern.
AB  - A series of studies have shown that humor is associated with close interpersonal
      relationships and effective in reducing stress, which in turn enhances empathy.
      Therefore, it was hypothesized that humor and empathic concern would be
      positively correlated. The Empathic Concern subscale of the Empathy
      Questionnaire, the Coping Humor Scale, the Multidimensional Sense of Humor Scale,
      and the Situational Humor Response Questionnaire were given to 124 subjects.
      Scores on the Empathic Concern subscale were significantly correlated with those
      on each of the humor scales. Types of humor may be an important variable in the
      relationship between empathic concern and humor. Both humor and empathic concern
      are associated for people with emotional intelligence who use these to interact
      effectively with other individuals. As such, it was suggested that exploration
      would yield a relation between humor and emotional self-awareness, which is also
      associated with emotional intelligence.

PMID- 11293037
TI  - Parents who report using illicit drugs: findings and implications from the
      DRUGNET study.
AB  - In recent years, a national discussion has emerged concerning what parents should
      tell their children about their own past drug use. DRUGNET is an ongoing, on-line
      survey of successful, healthy, adults who occasionally use illicit drugs. This
      paper reviews data from a subset of this survey, namely, those respondents who
      were parents with self-reported use of at least one illicit drug. The sample (n =
      325) was predominantly white men who reported having above average education and
      household incomes. Their mental health as measured by the General Well-being
      Schedule was similar to the national norm. Respondents reported using drugs to
      manage parental stress and expressed concerns over how to communicate with their
      children and legal risks related to their own drug use. The limitations and the
      implications of these data are discussed.

PMID- 11293038
TI  - Hopelessness and perfectionism.
AB  - In a sample of 39 undergraduates, hopelessness scores were associated with two
      aspects of perfectionism, concern over mistakes and doubts over performance.

PMID- 11293039
TI  - Unidimensionality of life satisfaction and its relation to social desirability: a
      confirmatory study of a short form of the Life Satisfaction Scale.
AB  - This study investigated construct validity of a short version of the Life
      Satisfaction in the Elderly Scale developed from an exploratory factor analysis
      in 1990 of the original version of Salamon and Conte's Life Satisfaction scale.
      First, a confirmatory factor analysis (maximum likelihood method) was conducted
      on 149 adult and elderly Italians to assess whether the latent variable of the
      Life Satisfaction Short Form scale was adequately represented by one factor.
      Analysis showed a good fit for the proposed unidimensional model, the items
      achieved good internal consistency on the scale, and no age differences arose in
      the score for the Life Satisfaction factor. Second, the correlations between the
      items measuring Life Satisfaction and the Eysenck 1985 Lie scale indicated that
      the items on the Life Satisfaction Short Form are largely independent of social
      desirability for younger and older adults.

PMID- 11293040
TI  - Test-retest reliability and factor structures of organizational citizenship
      behavior for Hong Kong workers.
AB  - In 1990 Podsakoff, MacKenzie, Moorman, and Fetter developed a scale to measure
      the five dimensions of organizational citizenship behavior. Test-retest data over
      15 weeks are reported for this scale for a sample of 82 female and 32 male
      Chinese tellers (ages 18 to 54 years) from a large international bank in Hong
      Kong. Stability was .83, and there was no significant change between Times 1 and
      2. Analysis indicated the five-factor structure and showed it to be a reliable
      measure when used with a nonwestern sample.

PMID- 11293041
TI  - Factor analytic properties of the Quality of Life Profile: examination of the
      nine subdomain Quality of Life Model.
AB  - The Quality of Life Profile is a 54-item multidimensional measure of quality of
      life. The measure is based upon a theoretical approach that considers quality of
      life to include satisfaction with nine subdomains of functioning. To date, the
      factor structure of this 54-item collection has not been examined. To do so, an
      examination was made of the factor structure that emerged from an administration
      to 219 gay men, half of whom were HIV+. Analysis indicated that seven subdomains
      were clearly represented in seven of the 11 factors that emerged. One subdomain
      was fractured into two factors and one subdomain did not appear in the factor
      structure. Two minor factors appeared to represent issues that may be especially
      important to gay men living in the HIV era. The study provides insights into the
      structure of quality of life among gay men living in Ontario.

PMID- 11293042
TI  - Development and psychometric properties of the Student Worry Questionnaire-30.
AB  - Described are the development and initial psychometric properties (Ns = 50 and
      188) of a self-report measure, the Student Worry Questionnaire-30, for use with
      college undergraduates. Exploratory principal components analyses (Ns = 388, 350,
      and 396) with oblimin rotation indicated six domains of worrisome thinking,
      financial-related concerns, significant others' well-being, social adequacy
      concerns, academic concerns, and general anxiety symptoms. The total score and
      scale scores showed internal consistency of .80 to .94. Also, test-retest
      reliability analyses (.75 to .80) support consistency of responses over 4 wk.
      Strong evidence for convergent validity) was indicated. Confirmatory factor
      analysis confirmed the fit of the 6-factor oblique model. Limitations of the
      present studies, and directions for research are discussed.

PMID- 11293043
TI  - Preliminary evaluation of an abstinence-based program for 7th grade students from
      a small rural school district.
AB  - The purpose of this study was to investigate the effects of an abstinence-based
      program designed for 7th grade students (n = 59) from a rural school district.
      Analysis suggested that after the program more students intended to avoid having
      sex before marriage but no change was noted for knowledge, attitudes, and self
      efficacy.

PMID- 11293044
TI  - Family myths in romantic fiction.
AB  - Three types of myths frequently appearing in contemporary romantic fiction deal
      with traditional family values, spousal relationships, and love. Several myths
      belonging to each type are illustrated and analyzed. It is argued that by
      naturalizing some behaviors and idealizing others, romantic novels not only may
      indoctrinate their readers with a patriarchal ideology but also may inculcate
      upon them pathogenic family processes.

PMID- 11293045
TI  - Assessing the dimensionality of the Singhapakdi, Vitell, and Kraft measure of
      moral intensity.
AB  - In a sample of 105 students, the dimensionality of a moral intensity scale
      developed by Singhapakdi, Vitell, and Kraft in 1996 was assessed. Principal
      components analysis yielded a one-factor solution across 10 ethics scenarios,
      indicating that moral intensity may be treated as a unidimensional construct in
      some situations.

PMID- 11293046
TI  - Lateral feature displacement and perceived facial attractiveness.
AB  - Pairs of vertically adjacent facial features were laterally displaced in the same
      or opposite direction. Undergraduates rated the resulting images on
      attractiveness. Displacements were first made on normal faces. Symmetric faces
      were not rated more attractive than normal controls. Faces with two alternating
      adjacent pairs were rated lower than faces with one or no alternating pairs. In
      Exp. 2, the same displacements were made from symmetrical faces to control for
      distance. Symmetric faces again were not rated higher than normal ones, and both
      conditions were considered more attractive than faces with any type of
      displacement. This latter result suggests a greater sensitivity to feature
      displacement when performed from symmetry.

PMID- 11293047
TI  - Attributions of cause for vehicular accidents: effects of participants' sex,
      information level, and instructions to identify with the actor.
AB  - Attributions of cause for vehicular accidents were studied by means of a
      questionnaire presenting fictional accident vignettes involving a main character
      (the actor). The randomly assigned questionnaires presented either Instructions
      for Identification with the actor or for Nonidentification. Each questionnaire
      randomly presented six vignettes, two vignettes randomly drawn from each of three
      Information Levels (Low, Medium, and High). Participants were undergraduates, 24
      men and 26 women, who gave the cause of each accident in writing and rated that
      cause on three dimensions using 7-point scales for Internality-Externality,
      Stability, and Globality. Identification Instructions were associated with more
      External ratings than were Nonidentification Instructions. The High Information
      Level was associated with more Internal and higher Globality ratings than the
      lower Levels. In interactions for participants' sex, women under Identification
      Instructions gave more External ratings and lower Stability ratings than women
      given Nonidentification Instructions or men in the Identification condition.

PMID- 11293048
TI  - Pyridostigmine bromide and the long-term subjective health status of a sample of
      female reserve component Gulf War veterans: a brief report.
AB  - The role of pyridostigmine bromide (PB) pills in explaining the long-term
      subjective health status of a sample of over 100 female Reserve Component Gulf
      War veterans was examined through regression analysis. Results fell just short of
      significance (p < .06) for the prediction of subjective health approximately six
      years after the war and were clearly not significant for the prediction of
      subjective health at previous times. Results parallel Golomb's 1999 RAND report,
      which found suggestive but not conclusive evidence for the possible adverse
      effects of Gulf War veterans' consumption of pyridostigmine bromide pills. Our
      data suggest that use of more than 10 pills may have been especially risky with
      respect to long-term subjective health.

PMID- 11293049
TI  - Attitudes of parents of nondisabled students regarding inclusion of disabled
      students in Nevada's public schools.
AB  - Opinions of 370 parents of students without disabilities about inclusive
      programming were compared with those obtained from a previous study of 65 parents
      of students with disabilities. Both groups of parents positively rated opinion
      statements favoring inclusion; however, parents of students with disabilities
      consistently rated inclusion-focused statements more positively than parents of
      nondisabled students.

PMID- 11293050
TI  - Implicit and explicit memory in junior high and college students.
AB  - This study compared the performance of 25 seventh and eighth grade boys and girls
      on tests of implicit and explicit memory to that of 34 men and women in college.
      The latter performed significantly better on the explicit memory test. Young
      adolescents showed a significant priming effect on the implicit memory test;
      college students did not. Findings suggest a ceiling effect for college students.
      The results support the distinction between implicit and explicit memory.

PMID- 11293051
TI  - Gay marriage affiliation and location in return of lost letters: reply to Waugh,
      Plake, and Rienzi (2000).
AB  - Reinspection of Waugh, Plake, and Rienzi's 2000 data allowed for several
      additional analyses. Statistical confirmation was found for no more negative
      attitudes toward gay marriage as measured by returned responses among churchgoers
      than among the general public. Confirmation was also found for their previous
      conclusion that the putative gay marriage controversy among Christian church
      attendees would be greater than among the general public, but for reasons
      different from those they proposed. Finally, it is argued that the limitations
      for the lost letter technique in "prohibiting fine distinctions" is not always
      correct because their analysis of one research question seemed not too subtle a
      distinction for the technique.

PMID- 11293052
TI  - Preliminary results of a pilot program on depression in patients with congestive
      heart failure.
AB  - While the sample size is too small to warrant conclusions, these preliminary
      results suggest that assessment of depression would be worthwhile for patients
      diagnosed with congestive heart failure. 32 out of 54 patients with congestive
      heart failure scored positive for depression. When psychiatric treatment was
      given, there was a decrease in depressive symptoms for four of the six patients
      at the 6-mo, retest. A decrease in depressive symptoms was found for two of the
      six untreated patients, and the remaining four patients had worse scores on the
      Zung Depression Inventory. Primary care physicians, who typically meet with such
      patients regularly, are encouraged to screen for depression, as their clinical
      assessments in this study were associated with scores on the Zung Depression
      Inventory. These observations support a full scale investigation with a much
      larger sample size and a requisite medical cost comparison.

PMID- 11293053
TI  - Apologies: genuine admissions of blameworthiness or scripted, sympathetic
      responses?
AB  - The present study assessed whether apologies, given when an implicit offense is
      committed, are a product of the perpetrator's attributions of blameworthiness or
      merely scripted, sympathetic responses given without discrimination. 139
      university students were manipulated to commit an implicit offense, accidental
      bodily contact with a confederate. The attributions that the perpetrator or
      student made for the incident were then recorded. The participants' attributions
      for the offense played a negligible role in predicting the elicitation of an
      apology. However, the participants' sympathy and desire to help the victim were
      somewhat associated with whether an apology would be delivered. Results suggest
      that apologies are not necessarily admissions of blameworthiness but may be in
      many cases scripted and or sympathetic responses.

PMID- 11293054
TI  - Psychological predictors of sexual behaviors related to AIDS transmission.
AB  - This study was designed to assess the differential value of several psychological
      variables with regard to predicting safe-sex behavior. A sample of 94 male and
      179 female undergraduate students, ranging in age from 16 to 66 years, were
      surveyed about sexual issues related to safe-sex practices. The survey included
      scales measuring participants' knowledge of transmission of AIDS, self-perception
      of safe-sex communication, fear and concern about AIDS, attitudes toward AIDS
      victims, and self-report of risky behavior. Several interesting relationships
      among predictor variables were found. For instance, favorable attitudes toward
      AIDS victims were positively correlated with knowledge about AIDS transmission,
      perceived communication with partners about safe sex, and fear of acquiring AIDS.
      However, only two predictor variables were independently predictive of self
      reports of risky sexual behavior; specifically, fear about AIDS transmission was
      positively correlated with risky behavior, while communication was negatively
      correlated with risky behavior. These data suggest a need for a model that allows
      for complex, reciprocal relationships between the cognitive, emotional, and
      behavioral components of safe-sex practice. Implications are applied to research
      with college populations.

PMID- 11293055
TI  - New studies of adults' responses to the Bender Gestalt.
AB  - The Bender-Gestalt test originated in 1936 with Lauretta Bender for evaluating
      perceptual and motor development of children 4 to 11 yr. old. Koppitz (1964)
      developed a scoring system for the test. Lacks (1984) contributed normative data
      for testing adults. Seven studies since Lacks' which have contributed to
      normative data of adults' responses to the Bender-Gestalt are reviewed here.

PMID- 11293056
TI  - Selected lifestyle and risk behaviors associated with adolescents' smoking.
AB  - A selected number of lifestyle and risk behaviors of adolescents in relation to
      their smoking were studied using both longitudinal and cross-sectional analyses.
      Data of a national sample of 4,431 nonsmoking adolescents who participated in the
      1989 Teenage Attitudes and Practices Survey and were re-interviewed in 1993 were
      analyzed. Adolescents who engaged in physical fights, engaged in drunk driving,
      and were risk-takers were more likely to be regular experimental smokers than
      adolescents who did not exhibit these behaviors. The data suggest that high-risk
      behaviors may cluster. Interventions may be necessary to target multiple risk
      behaviors and be more effective in changing adolescents' risk behaviors
      associated with smoking.

PMID- 11293057
TI  - College students who wear watches: locus of control and motivational sources.
AB  - 119 undergraduate college students were administered the Rotter I-E Scale and the
      Motivation Sources Inventory. Scores were compared for a group of 66 students who
      were wearing watches and 53 students who were not wearing watches. The former had
      higher scores on External locus of control and higher scores on a measure of
      Instrumental Motivation as anticipated.

PMID- 11293058
TI  - Self-reported proclivity to harass as a moderator of the effectiveness of sexual
      harassment-prevention training.
AB  - The interaction between the likelihood of males engaging in sexual harassment and
      the effectiveness of a 1-hr. sexual harassment-prevention training was explored
      in a laboratory study. An interaction of scores on the Likelihood to Sexually
      Harass Scale and training condition for 90 undergraduate men was found, such that
      sexual harassment-prevention training had a small negative effect on the
      attitudes of males with a high proclivity to harass.

PMID- 11293059
TI  - Geophysical variables and behavior: XC. What people consider strange: change in
      proportions of reports of Fortean phenomena over time.
AB  - The proportions of 3,667 reports classified as unusual or odd events within eight
      major categories for four contiguous blocks of time between 1770 and 1970 were
      compared for disconcordance. The major source of the disconcordance (phi = .52)
      of reports between the major categories and time was due to the decrease in the
      numbers of reports of falls of ice, rocks, and animals but increased numbers of
      reports of odd luminosities, labelled as unidentified flying objects, after the
      mid 1930s. One hypothesis to explain this result is that cultural changes in
      attributions for causes of natural phenomena may affect their designation as
      strange rather than mundane.

PMID- 11293060
TI  - Relations of some sociocultural variables and attitudes and motivations of young
      Arab students learning English as a second language.
AB  - This paper examined a number of variables pertaining to the sociocultural
      outlooks of 412 young Arab students learning English as a foreign language and
      the relation of their attitudes and motivations prior to their learning of the
      language. Analysis indicated clearly that certain variables appeared to be
      correlated with their attitudes and motivations more than others. Most of the
      students had maids in their homes, and the presence of a maid was associated with
      most of the psycholinguistic variables tested. Their previous learning experience
      of the language was positively correlated as was their knowledge of English
      stories. Having some sort of English games had the highest correlations (.25 to
      .41). Potential pedagogical implications of these results were discussed.

PMID- 11293061
TI  - Video streaming: pushing a swimming pool through a straw.
AB  - If someone asked you to move all the water from one swimming pool to another, you
      would try to use the biggest hose and the most pressure you could find to make
      the transfer relatively quick and easy. Moving a video file from one computer to
      another is very similar to moving all that water: there's usually a tremendous
      amount of data (lots and lots of water) and very little bandwidth (the size of
      the hose).

PMID- 11293062
TI  - The Lennart Nilsson Award.
AB  - This article takes a brief look at the photography of Lennart Nilsson as well as
      the history of, and the formation of a foundation to raise monies for the
      establishment of an award in his name. Subsequently, a board and an international
      nominating committee evolved to select individuals to receive the award. Honorees
      are chosen based on the merits of their efforts in scientific imagery that, like
      the photography of Nilsson, reveal the unseen in the natural world. Finally, this
      article discusses the work of the latest two recipients of the award and invites
      readers to participate in the nomination process.

PMID- 11293063
TI  - Choosing an adipose tissue depot for sampling. Factors in selection and depot
      specificity.

PMID- 11293064
TI  - Assays of lipogenic enzymes.

PMID- 11293065
TI  - Assays of adrenergic receptors. Including lipolysis and binding measurements.

PMID- 11293066
TI  - Transfection of adipocytes and preparation of nuclear extracts.

PMID- 11293067
TI  - Assay of membrane transport of long-chain fatty acids by adipocytes.

PMID- 11293068
TI  - Assays of glucose entry, glucose transporter amount, and translocation.

PMID- 11293069
TI  - Methods to study phosphorylation and activation of the hormone-sensitive
      adipocyte phosphodiesterase type 3B in rat adipocytes.

PMID- 11293070
TI  - Measurements of glucose conversion to its metabolites.

PMID- 11293071
TI  - Metabolite and ion fluxes and ion channels in brown and white adipocytes.

PMID- 11293072
TI  - Culture of adipose tissue and isolated adipocytes.

PMID- 11293073
TI  - Morphologic techniques for the study of brown adipose tissue and white adipose
      tissue.

PMID- 11293074
TI  - Cultures of adipose precursor cells from brown adipose tissue and of clonal brown
      adipocyte-like cell lines.

PMID- 11293075
TI  - Cultures of adipose precursor cells and cells of clonal lines from animal white
      adipose tissue.

PMID- 11293076
TI  - Cultures of human adipose precursor cells.

PMID- 11293077
TI  - Measurements of peptide and nonpeptide secretory products from adipocytes.

PMID- 11293078
TI  - Assessment of white adipose tissue metabolism by measurement of arteriovenous
      differences.

PMID- 11293079
TI  - Measurement of adipose tissue blood flow.

PMID- 11293080
TI  - Respiratory and thermogenic capacities of cells and mitochondria from brown and
      white adipose tissue.

PMID- 11293081
TI  - Measurements of white adipose tissue metabolism by microdialysis technique.

PMID- 11293082
TI  - Immunoassay measurements of leptin.

PMID- 11293083
TI  - Confocal microscopy of adipocytes.

PMID- 11293084
TI  - Cellularity measurements.

PMID- 11293085
TI  - Subcellular fractionation of adipocytes and 3T3-L1 cells.

PMID- 11293086
TI  - Quantification of lipid-related mRNAs by reverse transcription-competitive
      polymerase chain reaction in human white adipose tissue biopsies.

PMID- 11293087
TI  - Glycogen synthase activity in adipose tissue. Methods for freeze-clamping and
      assay.

PMID- 11293088
TI  - Assays of lipolytic enzymes.

PMID- 11293089
TI  - [Minimally invasive surgery in intracranial aneurysms].
AB  - INTRODUCTION: The use of minimally invasive procedures in neurosurgery permits a
      significant reduction in peri-operative morbidity and duration of hospital stay.
      The fronto-latero-basal (FLB) approach gives good exposure of the structures of
      the anterior and middle fossas with access to most aneurysms of the anterior
      circulation, thus avoiding extensive craniotomies and the use of brain
      retractors. OBJECTIVE: We present an analysis of 27 patients operated on to clip
      29 aneurysms of the anterior circulation using the FLB approach. PATIENTS AND
      METHODS: The study included 27 patients, 18 women and 9 men with an average age
      of 47.53 years. On clinical staging, using the Hunt and Hess scale, 12 patients
      were between 0 and 1, 8 at stage II, 6 at stage III and 1 at stage IV. RESULTS:
      The aneurysms were mainly on the internal carotid artery (16), middle cerebral
      artery (5), anterior communicating artery (5) and bifurcation of the carotid and
      middle cerebral arteries (3). The surgical operation lasted an average of 166.15
      minutes; it was possible to clip the artery in 28 cases (96.5%). Two patients
      died (of renal failure and of disseminated intravascular coagulation). Most
      patients were discharged with a score of 5 points on the Glasgow prognosis scale
      7.6 days after operation. CONCLUSIONS: Use of minimally invasive procedures such
      as FLB gives optimal functional and aesthetic results, with the advantage of
      being possible using the basic instruments available in any neurosurgical
      department, without depending on advanced technology.

PMID- 11293090
TI  - [Reliability of electrophysiological measurements of motor control].
AB  - OBJECTIVES: The aim of the study was the short term test-retest-reliability of
      electrophyisiological correlates of simple processes of the motor control, i.e.
      the execution (go) and the inhibition (no go) of a prepared motor response,
      evoked during the Continuous Performance Test (CPT). Our interest was centered in
      the reliability of the topographical P300-parameters described in previous
      studies, i.e. the localizations of the go and no go centroids and the no go
      anteriorization (NGA), which is the difference between the two centroid
      locations. A sufficient reliability is a basic requirement for the application of
      these new topographical parameters for the investigation of different psychiatric
      illnesses with suspected dysfunctions of prefrontal motor control, e.g.
      schizophrenias and affective illnesses, obsessive-compulsive disorders,
      personality disorders with deficits in impulse control, and in children with
      attention deficit hyperactivity disorder. PATIENTS AND METHODS: We examined 23
      healthy subjects who executed two versions of the CPT with an interval of 30
      minutes. After averaging the obtained evoked potentials of each subject, we
      determined the latencies, amplitudes and positive centroids, at the moment of the
      peak of the Global Field Power in a P300 time window. RESULTS: Statistical
      analysis revealed sufficient test-retest-reliabilities in comparison to other
      electrophysiological paradigms, mainly for the localizations of the go (r = 0.93;
      p = 10(-10)) and no go centroid (r = 0.85; p = 10(-4)), as well as for the no go
      anteriorization (r = 0.63; p = 10(-3)). CONCLUSION: These results are a
      prerequisite for the application of these topographical parameters as measures of
      the prefrontal motor control in different healthy and psychiatric populations.

PMID- 11293091
TI  - [Primary vertebral lymphoma].

PMID- 11293093
TI  - [Pattern electroretinogram in anterior ischemic optic neuropathy].
AB  - INTRODUCTION: Anterior ischemia optic neuropathy is defined as ischemia of the
      disc optic papilla nerve. The aetiology is multifactorial and causes ischemia of
      the optic disc and apoptosis of the nerve cells of the retina. OBJECTIVE: To
      study the retina of patients with anterior ischemia optic neuropathy by means of
      the electroretinogram pattern (PERG) to assess the function of ganglion cells of
      the inner layers of the retina. PATIENTS AND METHODS: We studied 12 patients
      referred from the Ophthalmology Department with the diagnosis of anterior
      ischemia optic neuropathy. The electrophysiological study consisted of PERG and
      PEV within 20 days of the episode. The latencies and amplitudes of the different
      components of the responses and the ratios of the PERG amplitudes were
      determined. RESULTS: No significant differences were seen in the P50 component of
      the PERG or the latency of the N95 component. However, statistically significant
      values were obtained for the amplitude N95. These differences were greater when
      measured from a nonlinear baseline. CONCLUSIONS: The PERG is useful for early
      diagnosis of patients with anterior ischaemia optic neuropathy. Measurement of
      the N95 is more useful when a nonlinear baseline is used. This shows dysfunction
      of the ganglion cells of the inner retina caused by ischaemia and retrograde
      degeneration of axons and cell bodies of the optic nerve.

PMID- 11293092
TI  - [Segmental motor paralysis caused by the varicella zoster virus. Clinical study
      and functional prognosis].
AB  - INTRODUCTION: Segmental motor paralysis of the limbs (SMP) complicates 2-3% of
      the cases of cutaneous herpes zoster. Viral invasion and inflammation of the
      motor neurons of the anterior horn cells by the varicella-zoster virus (VVZ)
      causes clinical weakness at the same time and site as the cutaneous eruption.
      OBJECTIVES: To analyze the clinical findings, complementary investigations and
      functional prognosis of patients with SMP at brachial plexus and lumbosacral
      levels. PATIENTS AND METHODS: We made a retrospective study of 10 patients with
      SMP admitted to the Hospital Universitario Gregorio Maranon de Madrid during 1989
      1999, aged between 38 and 84 years (6 women, 4 men). Neurological examination was
      done, including muscle balance, complementary studies including microbiology
      (serum and CSF serology, viral PCR-ADN), neurophysiology using MNR of the spine
      and plexuses and functional prognosis on the NDS, NSS and RANKIN scales. RESULTS:
      There is a close relationship between dermatome and myotome involvement (90%).
      The brachial and lumbosacral plexuses were equally affected (50%). Plasma and CSF
      VVZ serology was positive in 50% of the cases, permitting diagnosis of a patient
      with no cutaneous lesions (zoster sine herpete). Denervation of the myotomes
      involved and the paraspinal muscles was shown on neurophysiological studies. In
      most cases there was functional improvement, with complete functional recovery in
      80% of the cases after 12 months. CONCLUSIONS: VVZ should be considered amongst
      the aetiologies of SMP, even in the absence of cutaneous lesions (zoster sine
      herpete). The SMP coincides in time and place with the dermatome lesions. In most
      patients there is complete functional recovery within 12 months.

PMID- 11293094
TI  - [Comparative analysis of the clinical history and polysomnography in sleep
      disorders. Diagnostic relevance of polysomnography].
AB  - INTRODUCTION: The incidence of associate pathologies has been studied during the
      sleep, as well as the diagnostic efficiency of the clinical history. PATIENTS AND
      METHODS: Patients (n = 136) remitted by diverse services, have been studied. It
      has been carried out a complete polysomnography, as well as other supplementary
      studies (anxiety and depression tests, excessive daytime sleepiness Epworth's
      test, EEG and sleep notebook). RESULTS: The most common symptom turned out to be
      the primary snores, followed by the excessive daytime sleepiness and apneas. The
      results of the excessive daytime sleepiness Epworth's test and the anxiety and
      depression tests were not useful to differ among pathologies, not even between
      pathologies and patients with normal sleep. The percentage of diagnosis of
      suspicion confirmed by the polysomnography was of 39.7%, while in 11% of the
      total of patients it was observed the existence of more than a pathology of the
      sleep. In 49.3% of the cases the polysomnographic diagnosis was completely
      different from the diagnosis of suspicion. Among the patients with clinic
      suspicion of apnoea, in 48.3% of the cases the existence of the same one was
      verified, although in 14.6% it was associated with other pathologies. In 51.7% of
      the patients it was not possible to confirm this pathology. CONCLUSIONS: The
      clinical history is not enough for the diagnosis of the pathologies of the sleep.
      On the other hand, the existence of associate pathologies diminishes the value of
      several 'screening-methods'. Therefore, it is fundamental to carry out a complete
      polysomnography in all the patients that present any sleep disorder on the part
      of doctors that approach the problem of the sleep in a global way and not only
      thinking in the possible existence of syndrome of sleep apnoea.

PMID- 11293095
TI  - [PASS neurocognitive dysfunction in attention deficit].
AB  - INTRODUCTION: Attention deficit disorder shows both cognitive and behavioral
      patterns. OBJECTIVE: To determine a particular PASS (planning, attention,
      successive and simultaneous) pattern in order to early diagnosis and remediation
      according to PASS theory. PATIENTS AND METHODS: 80 patients were selected from
      the neuropediatric attendance, aged 6 to 12 years old, 55 boys and 25 girls.
      Inclusion criteria were inattention (80 cases) and inattention with hyperactive
      symptoms (40 cases) according to the Diagnostic and Statistical Manual (DSM-IV).
      Exclusion criteria were the criteria of phonologic awareness previously reported,
      considered useful to diagnose dyslexia. A control group of 300 individuals, aged
      5 to 12 years old, was used, criteria above mentioned being controlled. DN:CAS
      (Das-Naglieri Cognitive Assessment System) battery, translated to native
      language, was given to assess PASS cognitive processes. Results were analyzed
      with cluster analysis and t-Student test. Statistical factor analysis of the
      control group had previously identified the four PASS processes: planning,
      attention, successive and simultaneous. RESULTS: The dendrogram of the cluster
      analysis discriminated three categories of attention deficit disorder: 1. The
      most frequent, with planning deficit; 2. Without planning deficit but with
      deficit in other processes, and 3. Just only a few cases, without cognitive
      processing deficit. Cognitive deficiency in terms of means of scores was
      statistically significant when compared to control group (p = 0.001).
      CONCLUSIONS: According to PASS pattern, planning deficiency is a relevant factor.
      Neurological planning is not exactly the same than neurological executive
      function. The behavioral pattern is mainly linked to planning deficiency, but
      also to other PASS processing deficits and even to no processing deficit.

PMID- 11293096
TI  - [The use of afterimages in the diagnosis of Alzheimer's disease].
AB  - INTRODUCTION: For the first time visual after-images have been used in patients
      with Alzheimer's disease (AD). This is a simple, non-invasive system for analysis
      of visual pathway function, disorders of which it is hoped may be related to the
      patient's condition. OBJECTIVE: To obtain a method for early diagnosis which may
      also be used for follow-up and evaluation of the disease over a the course of
      time. We wished to ascertain whether patients with AD have alterations in the
      perception of visual after-images, and ascertain whether use of after-images is
      effective. PATIENTS AND METHODS: We used a portable perimeter for post-images in
      20 patients with Alzheimer's disease and in 20 normal persons. The results of two
      different tests were analysed, measuring the time taken for the after-image to
      disappear from the visual field of those being examined and trying to detect
      whether there was a relationship between the state of the person and the results
      of the test. It was shown statistically that the time taken for the after-image
      to disappear was less in the patients than in healthy persons, and this rapid
      rate of disappearance is directly related to the severity of the disease.
      CONCLUSION: We consider that the use of after-images is simple, effective and
      useful for early diagnosis and confirmation of patients with EA and their follow
      up.

PMID- 11293097
TI  - [Lamotrigine in refractory partial and general epilepsies].
AB  - INTRODUCTION: Lamotrigine (LTG) is a new antiepileptic drug that it has proved to
      be efficacious in treating patients with partial and generalized tonic-clonic
      seizures in adjunctive and monotherapy. It has similar efficacy in comparison
      with carbamazepine and phenytoin with a minor number of adverse experiences.
      PATIENTS AND METHODS: We report the use of LTG in adjunctive therapy in 106
      adults patients with refractory epilepsy (efficacy and safety) with partial and
      generalized seizures, with follow-up to 3.4 years. The LTG mean doses used was
      273 mg/day. RESULTS: 66% of patients experienced a > or = 50% reduction in
      seizure frequency, with 30% in remission. Both partial, secondarily generalized
      and generalized seizures showed significant reductions with LTG treatment. LTG
      was well tolerated in our patients. Side effects were minor. No case of rash was
      seen. CONCLUSION: LTG is a excellent agent for adjunctive therapy in refractory
      epilepsy.

PMID- 11293098
TI  - [Gabapentin in 50 patients with epilepsy].
AB  - OBJECTIVE: To evaluate monotherapy treatment with the anticonvulsant drug
      gabapentin, its efficacy and tolerability when used in patients with partial and
      secondary generalized partial epileptic seizures of recent onset who had not
      received treatment or who, in spite of treatment with other antiepileptic drugs
      failed to attain control over their seizures. PATIENTS AND METHODS: We made an
      open prospective study of 50 patients diagnosed as having partial and secondarily
      generalized partial epileptic seizures. The patients were given treatment at
      their first visit and them regularly followed up for two years. Treatment was
      given progressively until a maintenance dose of 1.200 mg/day was reached, and the
      dose them adjusted individually. RESULTS: We included 50 patients in the study;
      78% were treated with gabapentin. Ten percent stopped this treatment because it
      was ineffective. All the patients who continued their treatment with gabapentin
      had their seizures reduced by over 50%. This reduction in the number of seizures
      is statistically significant (p < 0.05) for patients with partial and secondarily
      generalized partial seizures. Twelve percent of the group of patients stopped
      their treatment because of side-effects. CONCLUSIONS: When the results of our
      study are evaluated and compared with those published in the literature, it may
      be seen that gabapentin is a safe, effective drug which is well tolerated when
      used as monotherapy for the treatment of patients with partial seizures.

PMID- 11293099
TI  - [Joint presentation of facial hemangioma, posterior fossa malformation, and
      carotid-vertebral hypoplasia (Pascual-Castroviejo syndrome II): report of 2 new
      cases].
AB  - INTRODUCTION: The association of external capillary hemangiomas with intracranial
      malformations (vascular or nonvascular) was first described by Pascual
      Castroviejo in 1978. The commonest anomalies found included: Dandy-Walker
      syndrome, cerebellar hypoplasia, arterial angiomas and alterations in the origin
      or distribution of the main cerebral arteries. In 1996 the same author named it
      the 'hemangiovascular complex syndrome'. The syndrome association is very
      similar, perhaps even identical, to that recently described in the English
      literature under the heading of PHACE. CLINICAL CASES: We describe two new cases
      of facial hemangioma, Dandy-Walker type posterior fossa malformation and
      hypoplasia of the carotid-vertebral trunk ipsilateral to the facial hemangioma.
      The first patient, a three year old girl had needed a ventriculo-peritoneal shunt
      for hydrocephalus secondary to a Dandy-Walker malformation. During the third
      month she had severe symptoms of laryngeal obstruction due to the angiomatous
      lesion and was satisfactorily treated with corticosteroids. At the present time
      her psychomotor development seems normal on neurological examination and
      evaluation. The second patient, a thirteen year old boy, besides showing the
      characteristic features of this syndrome also had attention-deficit hyperactivity
      and clumsy movements. In both cases the facial hemangioma was present at birth
      and gradually became smaller although it did not disappear completely.
      CONCLUSION: It is important to know about this neurocutaneous syndrome to avoid
      confusion with similar conditions such as the Sturge-Weber syndrome, so as to
      carry out suitable clinical investigations: cerebral magnetic resonance, angio
      resonance of the intracranial vessels and supra-aortic trunks, arteriography,
      echocardiography and ophthalmological assessment and to prevent signs of upper
      respiratory tract obstruction which may be very serious.

PMID- 11293100
TI  - [Idiopathic spinal cord herniation. Presentation of a new case and review of the
      literature].
AB  - INTRODUCTION: Idiopathic herniation of the spinal cord is a rarely diagnosed
      condition. It is important since this cause of paraparesis is potentially curable
      if diagnosis is made early. Our aim is to report a new case, review the relevant
      literature, describe the radiological findings and consider the etiopathogenic
      findings. CLINICAL CASE: We report the case of a 56 year old man with increasing
      difficulty in walking attributed to stenosis of the lumbar spinal canal, which
      did not improve after laminectomy. On examination he had sensory and motor
      deficits compatible with the Brown-Sequard syndrome. Dorsal MR showed ventral
      displacement of the thoracic spinal cord with disappearance of the anterior
      subarachnoid space together with a posterior arachnoid cyst at the same site. A
      further operation was done at the same place and the cyst removed. However, it
      was impossible to free the spinal cord since there was severe spinal
      arachnoiditis. The patient made little improvement. CONCLUSIONS: Herniation of
      the spinal cord is a rarely diagnosed condition. After careful study of the
      literature it seems that all patients present in a similar manner. Clinically
      there is a disorder of gait compatible with the Brown-Sequard syndrome. On MR
      there is sudden ventral displacement of the thoracic spinal cord, associated in
      some cases with an arachnoid cyst. When surgery is effective there is great
      improvement, so this diagnosis should be remembered in all cases of progressive
      paraparesis.

PMID- 11293101
TI  - [Neurosarcoidosis. Apropos of a case and review of the literature].
AB  - INTRODUCTION: Sarcoidosis is a disease of unknown cause, characterized by the
      presence of non-caseating granulomas in many organs. Neurological involvement is
      rare and only occurs in 5-7% of the patients, usually during the first two years
      after onset of the disease. The neurological findings vary depending on the site
      of the lesions. The treatment of choice is with glucocorticoids for at least 6-12
      months. Some patients in whom this treatment fails or leads to intolerable side
      effects may respond well to immunosuppressive drugs and/or radiotherapy. CLINICAL
      CASE: We present the case of a 31 year old man who complained of severe headache.
      He was referred to our department with the diagnosis of neurosarcoidosis and
      progressive neurological deterioration on conventional treatment. Holocranial
      radiotherapy with Co60 (30 Gy in 10 sessions) was given. Three months after this
      treatment had been given there was clinical improvement. CONCLUSIONS:
      Radiotherapy may be an effective alternative when other treatment fails or
      glucocorticoids cause intolerable toxicity. The recommended dose is between 12
      and 30 Gy, divided into 150-300 cgy/day.

PMID- 11293102
TI  - [Cerebral perfusion during word repetition in epileptic patients].
AB  - OBJECTIVE: To localize the cortical regions for language in patients who are to
      have brain surgery. PATIENTS AND METHODS: We made a SPECT (Single Photon Emission
      using Computerized Tomography) study of cerebral perfusion in 14 patients with
      drug-resistant temporal epilepsy who were candidates for brain surgery. The
      patients were selected consecutively from those attending for surgical
      assessment. We selected the patients in whom two 99mTc-HMPAO studies could be
      done in the same week: one without sensory stimulation and one whilst listening
      and repeating a series of ordinary words in fairly frequent use. The two studies
      were assessed qualitatively (on a 16 colour image scale, with a background
      subtraction of 20% and standardized to the point of maximum uptake). Changes were
      considered to be significant when a greater intensity of two colours was
      localized and semiquantitative (with regular areas of interest, of 4 x 4 pixels,
      placed on the region in which the qualitative change was observed and referenced
      to cerebellar activity). RESULTS: We found increased perfusion in the temporo
      parietal regions in 11 of the 14 patients. In most (9/14 cases) this was
      bilateral and in two cases on the left only. We observed a certain predominant
      pattern: a bilateral increase in temporal perfusion, involving the more anterior
      regions of the left hemisphere and also the middle and posterior regions of the
      right hemisphere. The maximum percentage increase in perfusion on
      semiquantitative assessment was 12%. CONCLUSION: Although the changes seen may
      correspond to activation in the cortical regions related to different cerebral
      functions, we consider that with the SPECT technique one may detect changes in
      perfusion of the regions of the brain which are involved in language processing.

PMID- 11293103
TI  - [Spasmodic torticollis and vertebral hemangioma].
AB  - INTRODUCTION: Spasmodic torticollis in young patients should give rise to a
      clinical suspicion that this is secondary to another primary disorder. Therefore
      a series of diagnostic tests should be carried out before it is labelled as
      idiopathic. CLINICAL CASE: The patient was a thirty year old man who had had
      difficulty in writing with his right hand since childhood. At the age of 20 years
      he was diagnosed as having writer's cramp and idiopathic spasmodic torticollis.
      On general physical examination no abnormalities were found. On neurological
      examination he had: absence of reflexes of both arms, limited but painless
      rotation of the neck towards the left and hypertrophy of the left trapezius
      muscle. Laboratory, neurophysiological and neuroimaging investigations seeking a
      secondary cause for the torticollis were all normal. There were no Keyser
      Fleischer rings. Chest X-ray showed, dorsal scoliosis with convexity to the left.
      CAT and MR of the spine showed a hemangioma in the body of T1. On arteriography
      of the supra-aortic and vertebral trunks a hemangioma was found at T1 which
      received contrast material via a branch of the right thyro-bi-cervico-scapular
      trunk. Various treatments were tried (diazepam, Botox, Dysport, tetrabenazine,
      baclofen, etc.) with no improvement. A definite diagnosis of secondary
      torticollis could not be made since the hemangioma was supplied by a very narrow
      vascular pedicle, so embolization was contraindicated. CONCLUSION: Cervical
      spinal cord alterations may cause focal dystonia due to increased excitability of
      the spinal motor neurone, due to dysfunction of the disinhibitory descending
      reciprocal paths.

PMID- 11293104
TI  - [Inflammatory pseudotumor: differential diagnosis of tumors of the 4th
      ventricle].
AB  - INTRODUCTION: An inflammatory pseudotumour is a condition of unknown origin and
      inflammatory nature. It is rarely found in the CNS. We report a case of
      inflammatory pseudotumour localized to the IV ventricle and review the clinical
      characteristics of previously reported cases in order to outline the clinical
      profile of this condition. CLINICAL CASE: A 40 year old man was admitted to
      hospital complaining of a subacute condition involving difficulty in speaking and
      in moving his right arm and leg. On examination he had ocular deviation on
      initial gaze, a complete right Horner's syndrome, right supranuclear facial
      palsy, dyssynergy-asymmetry on the right finger-nose test and a dissociated
      sensitivity disorder of the left arm. On MR of the brain there was a space
      occupying lesion, nodular in form and fixed to the roof of the fourth ventricle.
      The histopathological report on the specimen removed by surgery stated it to be
      an inflammatory pseudotumour. On a MEDLINE search for reported cases of
      inflammatory pseudotumour of the CNS, 27 were found since 1967. Four cases,
      including ours, involved masses growing into the interior of the fourth
      ventricle. CONCLUSIONS: Inflammatory pseudotumour of the CNS is a condition
      affecting young adults, with a slight male predominance and some association with
      clinical and analytical data suggesting autoimmune dysfunction. The
      intraventricular site, particularly within the fourth ventricle, is relatively
      common (4/28) and is usually associated with clinical features of dysfunction of
      the posterior fossa and/or intracranial hypertension. We consider that
      inflammatory pseudotumour should be included in the differential diagnosis of
      tumours of the fourth ventricle.

PMID- 11293105
TI  - [Usefulness of the blink reflex in a case of brainstem neuro-Behcet's disease].
AB  - INTRODUCTION: Brainstem is the most frequently affected structure in neurobehcet
      disease. Brainstem auditory evoked responses (BAER) and magnetic resonance
      imaging (MRI) have been employed in early diagnosis of the disease. We present
      here a case of neurobehcet disease which brainstem lesion was suspected by blink
      reflex and corroborated by MRI. BAER were normal in this case. CLINICAL CASE: The
      patient was a woman, 49 years old, diagnosed from Behcet's disease. Clinical
      symptoms consisted of dizziness, headache, nausea, vomiting and bilateral
      tinnitus preceded by fever in the previous days. Neurological examination showed
      increased tendon reflexes and adiadochokinesis. Cerebrospinal fluid was
      inflammatory but aseptic. Computerised tomography and BAER were normal. Blink
      reflex recording showed abnormalities after the stimulation of the right
      supraorbital nerve in R2 component, ipsilateral and contralateral, the remainder
      components being normal. This finding was compatible with a lesion in the spinal
      tract-nucleus of the right trigeminal nerve. Cranial MRI showed several areas of
      high signal intensity in protuberancial calotte and spinal tract-nucleus of the
      trigeminal nerve. The patient improved after prednisone and chlorambucil combined
      therapy. Serial blink reflex studies were normal, while the patient was
      asymptomatic. CONCLUSION: These results indicate that determination of blink
      reflex together with BAER may be of help in the evaluation of a more extensive
      area of the brainstem in neurobehcet's disease, even in absence of trigemino
      facial symptomatology. Early diagnosis is important because of neurobehcet's
      morbi-mortality.

PMID- 11293106
TI  - [Hereditary ataxias in Cuba. Historical, epidemiological, clinical,
      electrophysiological and quantitative neurological features].
AB  - OBJECTIVE: This review has been designed to describe the main clinical,
      epidemiological, electrophysiological, molecular and quantitative neurological
      characteristics in SCA2. DEVELOPMENT: The prevalence rate of patients with ataxia
      in Holguin province is 43 per 100,000 inhabitants. The prevalence of family
      members at risk of having this disorder is 159.33 per 100 thousand in this
      province. The main neurophysiological abnormality observed was reduction in the
      amplitudes of sensory potentials. These alterations are the expression of a
      predominantly axonal peripheral lesion with signs of myelin damage. Techniques of
      quantitative neurology were developed for evaluation of the main disorders of
      coordination such as asymmetry and adiadochokinesis. In Cuba 125 families have
      hereditary ataxia, 772 patients and 8 to 10,000 family members are at risk of
      developing this condition. Seventy percent of the patients with ataxia are
      concentrated in Holguin province. The most severely affected towns are Baguanos
      (a rate of 129.20 per 100,000 inhabitants), Holguin (71.85 per 100,000) and
      Cacocum (69.83 per 100,000). These are the highest rates in the world.
      CONCLUSIONS: The commonest molecular form in Cuba is the SCA2, observed in 120
      families. Clinically it is characterized by a cerebellar syndrome associated with
      disorders of eye movements and osteotendinous reflexes.

PMID- 11293108
TI  - [Cognitive deterioration in Huntington disease].
AB  - OBJECTIVES: To review, summarize and update data on the pattern of cognitive
      deterioration in Huntington's disease (HD). DEVELOPMENT: HD represents a paradigm
      of frontostriatal dementia in which cognitive deterioration affects three large
      domains: memory, executive and visual-spatial functions. Episodic explicit memory
      deficit mainly affects the processes of information recovery, whilst changes in
      implicit memory are impaired in learning procedures but not in priming. Executive
      dysfunction constitutes an essential characteristic, affecting the working
      memory, attention, sequencing and planning. Complex visual-spatial functions are
      severely affected and this may affect recognition of complex figures and facial
      gestures. Some of these mental changes may be detected during preclinical stages.
      At the present time, since it is possible to make a definite genetic diagnosis
      and there is neuropathological data on HD, this condition is considered to be an
      excellent clinical model for the study of the cognitive functions carried out by
      the cortico-striatal circuits. CONCLUSIONS: Using a multidisciplinary approach a
      cognitive model has been established in which the corpus striatum is considered
      to be the basic structure for selection of information which will generate the
      appropriate response, both motor and behavioral, for the context involved. Loss
      of this capacity leads to mental rigidity and perseveration in conduct, which are
      typical of the cognitive disorders of HD.

PMID- 11293107
TI  - [Neuropsychological changes in epilepsy].
AB  - OBJECTIVE: The neuropsychological assessment of the epileptic patient is a very
      important aspect of diagnosis and treatment. It may be used to contribute to
      localization of the hemisphere involved in the seizures, differentiate situations
      of anxiety or depression or when planning treatment for rehabilitation. We review
      the different aspects of neuropsychological changes in patients with epilepsy.
      DEVELOPMENT: Firstly we review the different tests used in the neuropsychological
      assessment of epilepsy. Dodrill's neuropsychological battery of tests, in which
      the patients score less than the controls, is the most commonly used. We then
      evaluate and study the so-called 'transient cognitive disorder'. We also study
      memory problems in epilepsy. There may be episodes of seizures with amnesic
      features ('amnesic epileptic seizures'). Finally, the possibility of
      neuropsychological dysfunction secondary to antiepileptic drugs should always be
      considered. CONCLUSIONS: Epileptic patients have lower scores than persons taken
      as controls for the results of various neuropsychological tests, although there
      is less difference between the two groups when the patient group is made up of
      persons with a normal intelligence quotient. Transient cognitive involvement is
      common in epileptics and may cause underachievement at school or psychological
      problems. Memory disorders, particularly subjective, are common in epileptics,
      although neuropsychological tests other than those generally used may be
      necessary to evaluate this. It is possible that such memory disorders, if
      occurring as seizures, may be due to amnesic partial crises, which should always
      be differentiated from the diagnosis of transient global amnesia. Almost all
      antiepileptic drugs can cause negative neuropsychological effects, especially the
      benzodiazepines and barbiturates.

PMID- 11293110
TI  - [Physiopathology of respiratory insufficiency of neuromuscular origin].
AB  - OBJECTIVE: To review the mechanisms involved in the appearance of respiratory
      failure in patients with neuromuscular disorders. DEVELOPMENT: The development of
      respiratory failure in patients with weakness of the respiratory muscles
      secondary to neuromuscular disease is not only due to the disease itself. There
      are also other mechanisms which contribute in varying degrees. These mechanisms
      are: 1. Alteration of the mechanical properties of the respiratory apparatus; 2.
      The appearance of muscle fatigue; 3. Alterations in the control of ventilation;
      4. Alterations in gas exchange during the night leading to loss of sensitivity of
      central and peripheral chemoreceptors. 5. Dysfunction of the upper airway, which
      favors the appearance of obstructive apnea during sleep. The part played by each
      of these mechanisms in the development of respiratory failure is different in
      each individual patient, depending on the type and severity of his particular
      illness. Ventilatory assistance at night has been shown to be effective in
      correcting respiratory failure during the day in these patients, probably by
      acting to a greater or lesser extent on all the different mechanisms involved.
      CONCLUSIONS: The origin of the respiratory failure seen in patients with
      neuromuscular diseases is due to many factors. Nocturnal ventilatory assistance
      is effective since it acts on all the different mechanisms involved.

PMID- 11293109
TI  - [Obstructive sleep apnea syndrome in childhood].
AB  - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a common problem in
      children. It is characterized by a partial airway obstruction associated with
      hypoxemia and hypoventilation rather than complete airway obstruction.
      DEVELOPMENT: Adeno-tonsillar hypertrophy is the leading cause but there are other
      risk factors like craniofacial abnormalities. OSAS may lead to neurodevelopmental
      abnormalities, growth and cardiorespiratory failure. It differs significantly
      from adult OSAS in its clinical presentation, polysomnographic findings and
      management. In spite of the fact that the diagnosis is often made on a clinical
      basis, the definitive and differential one only can be made by polysomnography.
      CONCLUSION: An overview of this pathology and the different polysomnographic
      parameters used are reported. Efforts to detect sleep apnea syndrome should be
      employed in children who present with the symptoms discussed. New guidelines for
      pediatric polysomnography should help standardize methods.

PMID- 11293112
TI  - [Distal spinal atrophy predominantly in the upper limbs. Presentation of a case].

PMID- 11293111
TI  - [Diagnostic difficulties in acute intermittent porphyria with neurological
      manifestations: apropos of 2 cases].

PMID- 11293114
TI  - The actin cytoskeleton, membrane lipid microdomains, and T cell signal
      transduction.

PMID- 11293113
TI  - [Acute astasia-abasia as the clinical presentation of an intracranial venous
      thrombosis].

PMID- 11293115
TI  - Btk and BLNK in B cell development.

PMID- 11293116
TI  - Diversity and regulatory functions of mammalian secretory phospholipase A2s.

PMID- 11293117
TI  - The antiviral activity of antibodies in vitro and in vivo.

PMID- 11293118
TI  - Mouse models of allergic airway disease.

PMID- 11293119
TI  - Selected comparison of immune and nervous system development.

PMID- 11293120
TI  - Raft membrane domains and immunoreceptor functions.

PMID- 11293121
TI  - Human basophils: mediator release and cytokine production.

PMID- 11293122
TI  - [Little interest within the EU in hazardous effects of alcohol. Sweden should use
      its chairmanship and try to make changes].

PMID- 11293123
TI  - [The forbidden fruit. On the surface again: new and old knowledge of toxic
      interactions between citrus fruits and certain drugs].

PMID- 11293124
TI  - [The first case of rabies in Sweden in 26 years. Inform travellers abroad about
      risks and treatment following suspected infection].
AB  - In June 2000, a case of rabies was diagnosed in Stockholm. The patient, a 19-year
      old woman, had been bitten by a dog in Thailand three months earlier. She was
      admitted with a 2-day history of pain and paresthesia at the exposure site (right
      arm), along with anxiety. Her neurological symptoms progressed, and during the
      following week she developed the typical signs of furious rabies. Despite
      intensive care, her condition deteriorated continuously, and she died 18 days
      after onset of symptoms. The diagnosis was not considered until five days after
      admission to the hospital. A saliva sample was obtained and the diagnosis
      confirmed by virus isolation in mouse neuroblastoma cells. Although Sweden is
      free of rabies, the diagnosis should be considered in patients with encephalitis
      after having visited a rabies endemic area. Tourists must be informed of the
      vital importance of post-exposure prophylaxis after suspected infection.

PMID- 11293125
TI  - [Medicine has much to learn from gender studies].
AB  - The issues raised in this article and illustrated with examples from gender
      research indicate new directions for public health, taking multidisciplinary
      gender scholarship into account. The changing potential of a gendered public
      health can be summarized in the following issues: new research questions and
      research areas, making differences within the group of women/men visible,
      introducing power analyses, developing theoretical frameworks as well as
      problematizing masculinities. Medicine has much to learn from gender research,
      especially in relation to reflexive approaches as well as current epistemology.

PMID- 11293126
TI  - [Malnutrition in the elderly--a challenge for health services].
AB  - Protein-energy malnutrition (PEM) remains common in elderly and chronically ill
      individuals. PEM is an independent risk factor for death in the elderly, and
      contributes to increased risk of infection, hip fracture, pressure sores and
      depression. Intervention studies indicate that nutritional treatment may confer
      positive effects in patients with chronic obstructive lung disease, during
      rehabilitation following hip fracture, and in elderly patients with multiple
      disorders. However, the scientific foundation for this is still weak, and for
      many wasting disorders there are no available data supporting a recommendation of
      nutritional treatment. Future challenges for clinical nutrition are the
      development of nutritional intervention programs and evaluation of adjuvant
      anabolic and inflammation modulating treatments for the elderly.

PMID- 11293127
TI  - [Report from Malmo Food Cancer Study. No socioeconomic differences when it comes
      to fat intake among middle aged population].

PMID- 11293128
TI  - [Report from an international consensus conference in Maastricht. Management and
      treatment of Helicobacter pylori infection].

PMID- 11293129
TI  - [European consensus on Helicobacter pylori infection in children].

PMID- 11293130
TI  - [Well-integrated chain of care results in better prognosis in severe brain
      injury].
AB  - The result of a project in the western region of Sweden regarding a multi- and
      interdisciplinary approach to patients with severe traumatic brain
      injury/subarachnoid bleeding is reported. The importance of early structured
      intervention and long-range follow-up by a rehabilitation team is stressed. The
      goal is to afford patients and their families/caregivers optimal care and support
      from the time of injury through rehabilitation. The project has resulted in an
      established clinical routine. Results indicate that patients treated in this
      manner attain a higher level of performance in a shorter period of time.
      Furthermore, results from one-year post-injury evaluation demonstrate a high
      degree of Life Satisfaction (Fugl-Meyer questionnaire) for most patients. This is
      a long-range study which will monitor patients for at least four years.

PMID- 11293131
TI  - [Vitamins are not always good!].

PMID- 11293132
TI  - [Vitamin A additives in food should be reduced].

PMID- 11293134
TI  - [Quality of doctor's certificate is sometimes as important for the patient as the
      medical treatment].

PMID- 11293133
TI  - [Interns must know more about insurance medicine! A questionnaire study shows
      that more education is required].

PMID- 11293135
TI  - [Who will solve the mystery of Marat's itching skin disease?].

PMID- 11293136
TI  - [Crime can be prevented--but not by the governmental model].

PMID- 11293137
TI  - [Can the physician's professional competence be substituted by a floppy disc?].

PMID- 11293138
TI  - [On the viability--a contribution to the debate on abortion].

PMID- 11293139
TI  - [Small cogs without evident Nazi ideology kept the killing going].

PMID- 11293140
TI  - [Last year I had one patient too many].

PMID- 11293141
TI  - [Physician's responsibility when travelling].

PMID- 11293142
TI  - [Let the everyday language decide when it comes to occurrence of gender-neutral
      words].

PMID- 11293143
TI  - [Follow-up of children in obstetrical clinical trials: research experience in
      Italy].
AB  - The effectiveness of treatments for the mother exposed to adverse events in
      pregnancy is not always interpreted in the light of possible effects on the
      child. The follow-up of infants is an important component of obstetric and
      perinatal audit not only in randomised clinical trials but as part of routine
      health care. The results of the 18 month's follow-up of children born from women
      recruited in the Italian Study of Aspirin in Pregnancy and in the Italian Trial
      on Nifedipine in Pregnancy are discussed. No significant differences emerged
      between treatment and no-treatment groups with respect to indicators of
      development and health status. Malformations, diseases, and other health problems
      showed no specific patterns and were much the same in the groups. Our findings
      suggest that the use of low-dose aspirin and calcium channel blocker nifedipine
      in pregnancy is safe with respect to the risks of malformation and of major
      impairment in development at 18 months of age.

PMID- 11293144
TI  - [Occult child abuse (opinions, considerations, personal observations)].
AB  - At the beginning of the statement the authors point out some lesser aspects of
      child's ill-treatment (previously suggested by them in other occasions) as
      expressions of very strict educational systems which strongly limit childrens'
      freedom or impose them several extrascholastic activities (such as: athletics,
      music with participation in competitive examination, studies of foreign
      languages, Latin and so on) where the child must excel in (composex of the
      "leader-child"). Then these authors suggest using the term "abuse" to mean
      lexically every excessive, undue, arbitrary use and not only "sexual". They point
      out the seriousness of abuse as far as juvenile exploitation is concerned both in
      case of manual labour and prostitution. But the pay particularly attention to the
      problem of sport when it is gone in for too intensively (as athletics). These
      authors infact sum up the harms that sport can cause when it is gone in for
      during the age under the stabilized puberty. Physical harms may occur especially
      during the practice of risky sports such as: Alpine skiing, cycling on the road,
      swimming combined with diving, fencing, boxing) and during tiring condition,
      while psychic harms can entail a fall in scholastic performances, irritability,
      insomnia, anxiety. The authors depreciate the behaviour of those parents who
      stimulate their children' aggressiveness during competitions and scold them when
      their performances are insufficient, or give them forbidden stimulants of
      hormonal anabolic drugs instead of taking care of their children in order to keep
      away from the arms mentioned above. However, after all these observations and
      considerations about competitive sports in juvenile age, these authors can firmly
      state that all this could be meant as an important aspects of the juvenile
      exploitation that must be taken in great consideration.

PMID- 11293145
TI  - Self-report assessment of recurrent abdominal pain.
AB  - Pain is the principal, and often the only symptom in cases of recurrent abdominal
      pain (RAP). The purpose of this study was to analyze the clinical background
      behind the pain symptom and the pain's capacity for differentiation in the
      diagnostic assessment of a group of 86 children suffering from RAP and observed
      at a pediatric gastroenterology service. The self-rating methods applied to the
      children included a verbal scale and a Visual Analogue Scale (VAS) for scoring
      the pain, and the Eland method, which is based on a graphic representation of the
      pain to enable its quantification and localization. Regardless of the pain
      assessment emerging from this study, the children were divided into 3 groups on
      the basis of a standardized diagnostic procedure, i.e. G1--upper gastrointestinal
      tract disease; G2--RAP with no apparent organic cause; G3--intestinal disease.
      RESULTS: The intensity of the pain fails to distinguish between the three groups,
      while other features seem more useful, e.g. variability in the pain's intensity,
      the number and location of painful sites, and the how the pain is graphically
      represented. Drawings typical of RAP with no apparent organic cause
      characteristically represent the pain more accurately and in greater detail,
      using more colors and a certain refinement in the performance of the drawing,
      with varying types of pain in subsequent episodes, and involving several
      abdominal and even extra-abdominal sites. In our experience, this method might
      contribute towards the completion and standardization of the child's clinical
      history and clinical evaluation. Such methods would have to be validated by
      further clinical studies, however.

PMID- 11293146
TI  - [Use and efficacy of treatment with porcine surfactant in newborns with birth
      weight < or = 1000 g: experience in 3 years].
AB  - OBJECTIVE: Evaluate the clinical response to the first and subsequent doses of
      natural surfactant for the treatment of respiratory distress syndrome (RDS) in
      extremely low birth weight infants (ELBWI). METHODS: Retrospective chart review
      of all ELBWI admitted to Neonatal Intensive Care Unit of Padova from July 1995 to
      December 1998 who received porcine surfactant for the treatment of RDS. Data
      collection included: (a) standard clinical variables (birth weight, gestational
      age, maternal steroid treatment, etc) (b) surfactant dosing), and (c) response to
      surfactant treatment as assessed by changes in the fraction of inspiratory oxygen
      (F1O2) and by the Oxygenation Index (OI). Outcome data (d) which included: death,
      duration of mechanical ventilation, duration of oxygen therapy, days in hospital
      stay, OI at 3,7 and 21 days of age, oxygen dependency at 28 days and at 36 week
      post conception were also collected. Data were analyzed by group comparison tests
      when comparing the groups that received one (S1), two (S2) or three (S3)
      surfactant doses and by multiple regression for the "predictors" of the response
      to surfactant treatment and for the "predictors" of outcome. RESULTS: Ninety-four
      ELBWI were evaluated. F1O2 at 12 hours after surfactant was reduced by more than
      one/third in 62% of the infants after the first dose, in 54% of the second doses
      and 61% of the third doses (non significant). S1, S2 and S3 groups had similar
      demographics and birth characteristics but the OI differed at 3 and 7 days (1.73
      +/- 1.39, 3.34 +/- 2.15 and 6.45 +/- 5.23 at day 3 and 1.42 +/- 1.27, 1.98 +/-
      1.83 and 4.03 +/- 3.91 at day 6 for S1, S2 and S3 respectively, p = 0.003). The
      response of exogenous was not found to be a significant predictor in our multiple
      regression model for major outcome variables such as oxygen dependency at 28 d or
      36 wk. CONCLUSIONS: In ELBWI in spite of the high percentages of good clinical
      response to the first, to the second and even to the third surfactant dose,
      response to surfactant treatment did not predict major general and respiratory
      outcomes.

PMID- 11293147
TI  - [Hormonal treatment of cryptorchism: indications and limitations].
AB  - Cryptorchidism is the most frequent anomaly of male genitalia. The major concerns
      of cryptorchidism are on psychological problems in childhood and infertility and
      increased cancer risk in adulthood. Medical treatment with various hormones has
      been used in the last 70 years to induce testicular descent, but some discrepancy
      exists in the various reports. In this paper, the efficacy on testicular descent,
      the effect on adult fertility and the inferences on risk of malignancy of the
      various hormonal strategies are reviewed and briefly discussed. From the
      literature data, a practical approach to the hormonal treatment of cryptorchism
      is suggested.

PMID- 11293148
TI  - [Sexually transmitted diseases in adolescents: clinico-epidemiologic findings].
AB  - Estimates of the global prevalence and incidence of sexually transmitted diseases
      in adolescents are limited. Recent prevalence estimates report over 333 million
      cases of the four major curable STDs in adults between the ages of 15 and 49: 12
      million cases of syphilis, 62 of gonorrhoea, 89 of chlamydia, and 170 of
      trichomoniasis. The vast majority of these cases are in developing countries such
      as East Asia and Pacific, Sub-Saharan Africa, Latin American and Caribbean where
      syphilis and gonorrhoea still have a high prevalence. However, CT genital
      infection is the most commonly reported bacterial STD. In 1996 this infection had
      been the most common of the nationally notifiable infectious disease in the
      United States and was estimated that there were 2.5-3.3 million new cases per
      year. It resulted that African-American adolescents 14 to 19 years of age have
      the highest rates of STDs of any racial/ethnic group of adolescents. In addition,
      viral "non-curable" STDs have become a prominent public health issue over recent
      years due to a marked increase in prevalence of HSV and HPV infections. In the
      United Kingdom the annual number of genital herpes has almost tripled during the
      past 15 years. It is now evident that the high rate of HSV asymptomatic infection
      plays an important and complex role in estimating epidemiological data. To date,
      HPV genital infection probably represents the most frequent STD. The young age of
      sexual activity onset and lifetime number of sexual partners are considered the
      highest behavioral risk factors.

PMID- 11293149
TI  - Psychological problems connected to the dietary restrictions in the adolescent
      with coeliac disease.
AB  - AIMS: To assess the influence of dietary restrictions on psychological
      development in adolescents with coeliac disease. DESIGN: Statistical analysis on
      coeliac patients on gluten-free diet who agreed to answer the questionnaire.
      SETTING: Children with coeliac disease on gluten-free diet followed by the
      Department of the Pediatric Division of the City Mayor Hospital, Chair of
      Paediatrics, Verona University. SUBJECT: 39 patients (15 male and 24 female) from
      10 years old to 21 who chose to answer a questionnaire of 25 questions dealing
      with the psychological implications of coeliac disease and with the need of
      following a particular dietary regime, in the presence of a psychologist. The
      questionnaire was made up of 6 SIGNALLING questions, 15 EVALUATING questions, 4
      FILTER questions. They also filled up an information sheet on the composition and
      social position of the family. RESULTS: Fathers were on average 45.5 years old,
      mothers 43. Only 2 parents had no educational qualifications. Father's
      professions were of various kinds, 22 mothers were housewives. Only 4 patients
      were only children, 22 had one brother or sister. 13 patients only out of 39
      claimed not to have been admonished by their parents, though, showed a
      conflictual relationship with food. The awareness of their difference from
      friends was: a) lack in children 10 to 12, b) uneasiness in adolescents 13 to 17,
      c) maturation and consensus in older patients. A significant number of patients
      feel different from their friends and these patients showed a latent envy to
      friends on free diet. A sense of latent envy towards the condition of
      independence was exhibited by patients who felt different from friends.
      CONCLUSIONS: The acceptance of a gluten-free diet is problematic for the majority
      of coeliac children and adolescents, particularly for those between 12 and 17. In
      this group the search of an individual personality is disturbed. Difficulties
      connected with gluten-free diet seem to be absent in the family environment,
      whereas difficulties emerge significantly when relating with friends. The number
      of cases of our study was limited but we consider these conclusions quite
      significant. DESCRIPTORS: Gluten-free diet, adolescents and children,
      relationship with parents, relationship with friends.

PMID- 11293150
TI  - [Antiepileptic drugs in pregnancy and malformations].
AB  - The use of antiepileptic drugs in pregnancy may be responsible of minor or major
      developmental abnormalities at birth or in infancy. The severity of effects and
      heterogeneity of that abnormalities might be related to a special genetic
      background giving the fetus a predisposition for epilepsy and vulnerability to
      major or minor anomalies. The authors report the case of a pregnant woman self
      prescribing of a politherapy without medical control. She gave birth to a newborn
      with sever intrauterin retardation, various dysmorphic features and moderate
      psychomotor delayed.

PMID- 11293151
TI  - [Ano-rectal malformations].

PMID- 11293152
TI  - [Genital ambiguities].

PMID- 11293153
TI  - [Sexuality and long-term results of hypospadias repair].

PMID- 11293154
TI  - [Bladder exstrophy].

PMID- 11293155
TI  - [Lower urinary tract obstruction].

PMID- 11293156
TI  - Mesenchymal tumors and tumor-like lesions of the female genital tract: a
      selective review with emphasis on recently described entities.
AB  - The diverse mesenchymal tumors and tumor-like lesions that occur within the
      female genital tract include a number of lesions that have only been recently
      characterized and others about which there is new information. In this group are
      the aggressive angiomyxoma, angiomyofibroblastoma, and cellular angiofibroma.
      Criteria for the distinction of these lesions are reviewed, as are the pathologic
      features of prognostic significance in assessing smooth muscle tumors of the
      vulva. The diagnostic problems that the epithelioid variant of smooth muscle
      tumors, both benign and malignant, may pose when they occur in various areas of
      the genital tract are discussed, particularly with regard to problems encountered
      in the ovary, a site where the diagnosis often is not considered. Recent
      information expanding the morphologic spectrum of fibroepithelial polyps of the
      genital tract is presented, and important non-neoplastic entities, including
      nodular fasciitis and the postoperative spindle cell nodule, are reviewed.
      Mesenchymal tumors of the various types seen in the soft tissues may be
      encountered anywhere in the female genital tract and have been the subject of
      particular recent interest in the ovary; issues relevant to differential
      diagnosis are reviewed.

PMID- 11293157
TI  - Clues to the pathogenesis of fallopian tube carcinoma: a morphological and
      immunohistochemical case control study.
AB  - The purpose of this study was to identify histopathological fallopian tube
      changes that might be related to the development of fallopian tube carcinoma
      (FTCA). Each of 14 unilateral cases of the latter was matched with 2 controls for
      age, hospital, and year of diagnosis. The uninvolved fallopian tube from patients
      with FTCA, all of which were of serous type, was compared to fallopian tubes from
      the same side in 28 matched controls. The features evaluated included plical
      bridging, trapped gland-like structures, inflammation, epithelial stratification,
      tufting, nuclear atypia, plical atrophy, luminal dilatation, and presence or
      absence of in situ carcinoma. The significant changes (p < 0.05) in the
      contralateral tubes of patients with FTCA were luminal dilatation (p = 0.0004),
      plical atrophy (p = 0.0015), and chronic inflammation (p = 0.0089). FTCA may
      therefore develop in tubes demonstrating histologic features of chronic healed
      salpingitis, findings that reflect bilateral tubal disease which apparently
      antedates the development of the FTCA. p53 stains were strongly positive in 9 of
      14 FTCAs and in 5 of 6 foci of in situ carcinoma found in the tubes with
      unilateral FTCA. No p53 staining was found in any of the contralateral tubes.
      Serous FTCAs may be etiologically related to antecedent bilateral healed chronic
      salpingitis and arise from in situ carcinoma in a background of atrophy.

PMID- 11293158
TI  - Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian
      types.
AB  - One thousand consecutive cases of surgically proven endometriosis were reviewed
      to evaluate the frequency and types of pelvic cancers that were associated with
      ovarian and extraovarian endometriosis. The frequency and types of histologic
      abnormalities present in the eutopic endometrium when cancers were noted in
      endometriosis were also evaluated. In the large subset of cases for which the
      authors were the primary pathologists and all foci of endometriosis were
      recorded, the frequency of malignancy was 10.8%. In contrast, the frequency was
      only 3.2% in cases diagnosed by others previously in our institution. Cancers
      were more commonly found in ovaries when endometriosis was present in that ovary
      (5%) compared to when endometriosis was present at other sites (1%). Clear cell
      and endometrioid carcinomas were the malignancies most commonly seen in ovaries
      containing endometriosis, while clear cell adenocarcinoma and adenosarcoma were
      most commonly seen in conjunction with extraovarian endometriosis. The
      association of endometriosis with endometrioid and clear cell carcinoma was much
      stronger than that of serous and mucinous tumors (p < .01). Concurrent
      endometrial pathology was commonly seen in cases of malignant transformation of
      endometriosis (32% of cases).

PMID- 11293159
TI  - CD44s expression is reduced in endometriotic lesions compared to eutopic
      endometrium in women with endometriosis.
AB  - Immunohistochemical expression of the standard form of CD44 (CD44s) was examined
      in archival formalin-fixed endometriotic and matching eutopic endometrial tissue
      obtained from 25 patients in proliferative (N = 16) and secretory (N = 9) stages
      of the cycle. CD44s was expressed in most eutopic endometria and endometriotic
      tissue. Its expression was significantly higher in secretory than in
      proliferative phase endometrium. It was low but detectable in 13 of 16
      proliferative phase biopsies. The majority of these endometria exhibited both
      glandular and stromal staining (63%). In the secretory phase, glandular cells
      exhibited a significantly greater intensity of staining compared to stromal
      cells. In endometriotic tissue, stromal cell CD44s expression did not differ
      between tissue types in either stage of the cycle. In contrast, glandular
      expression in endometriotic tissue during the secretory phase was reduced (p <
      0.05) compared to eutopic endometrium. It was absent in 66% of cases and reduced
      in the remaining cases. Our results indicate a correlation between CD44s
      expression and secretory differentiation of endometrial glands in the cycle,
      suggesting hormonal regulation of its expression. This cyclic pattern of CD44s
      expression was lost in corresponding endometriotic tissue. Reduced expression of
      CD44s in endometriotic tissue may provide insight into the pathophysiology of
      endometriosis.

PMID- 11293160
TI  - Classification of ovarian endometriotic cysts.
AB  - Current literature describes 3 different pathogenetic types of ovarian
      endometriotic cysts. Cortical invagination cysts arise when surface ovarian
      endometriotic deposits adhere to another structure (such as the broad ligament),
      blocking the egress of menstrual fluid produced by cycling endometriosis, which
      then collects and causes the ovarian cortex to invaginate. Surface inclusion cyst
      related endometriotic cysts develop when endometriotic tissue colonizes
      preexisting inclusion cysts. Physiological cyst-related endometriotic cysts occur
      when endometriosis gains access to a follicle, such as at the time of ovulation.
      To determine whether routine histological examination is of use in the
      classification of endometriotic cysts, and if so, whether such classification is
      of clinical relevance, we reviewed the histology of endometriotic cysts of 29
      women under 35 years of age. Young women were chosen so that ovarian cortex
      surrounding the endometriotic lining in invagination cysts could be identified by
      the finding of oocytes. Ten women (34%) had cortical invagination endometriotic
      cysts, but no inclusion or physiological cyst-related endometriomas were found.
      The remaining 19 women (66%) had unclassified endometriotic cysts, of which 14
      (48% of total) had a fibrous wall between the endometriotic lining and medulla
      and 5 had extensive destruction of ovarian tissue. We concluded that cortical
      invagination cysts were the only common diagnosable sort of the 3 types currently
      being investigated and that unclassified cysts required further study to
      determine their pathogenesis. Our study highlights the need for a prospective
      study using standardized pathological and clinical methods.

PMID- 11293161
TI  - The value of immunocytochemistry in distinguishing between clear cell carcinoma
      of the kidney and ovary.
AB  - Renal clear cell carcinoma rarely metastasizes to the ovary potentially mimicking
      a primary ovarian clear cell carcinoma. The immunocytochemical profiles of the
      two tumors were compared. Control groups of ovarian endometrioid and serous
      adenocarcinomas were also examined using the same antibody panel. Paraffin
      sections were studied with the immunocytochemical technique using eight
      antibodies. Renal clear cell carcinomas were positive for vimentin (8/12 cases),
      CK5/6 (0/12), 34 beta E12 (1/12), Ber-Ep4 (5/12), CA125 (0/12), ER (1/12), and
      PGR (1/12). Ovarian clear cell carcinomas showed positivity with vimentin (1/10
      cases), CK5/6 (2/10), 34 beta E12 (10/10), Ber-Ep4 (10/10), CA125 (8/10), ER
      (7/10), and PGR (6/10). Endometrioid adenocarcinomas were positive for vimentin
      (9/10 cases), CK5/6 (8/10), 34 beta E12 (10/10), Ber-Ep4 (9/10), CA125 (9/10), ER
      (9/10), and PGR (10/10). Eight serous adenocarcinomas were positive in all cases
      for all the antibodies except CK5/6 (7/8 cases) and 34 beta E12 (7/8 cases). All
      the tumors reacted for epithelial membrane antigen. This immunohistochemical
      panel allows clear cell carcinomas of kidney and ovary to be distinguished. The
      latter has a greater phenotypic similarity with serous and endometrioid
      adenocarcinomas than with renal clear cell carcinoma demonstrating yet again that
      these ovarian tumors share a common histogenetic origin.

PMID- 11293162
TI  - Expression pattern of the adhesion molecule CEACAM1 (C-CAM, CD66a, BGP) in
      gestational trophoblastic lesions.
AB  - CEACAM1 (CD66a, BGP, C-CAM) is an adhesion molecule of the carcinoembryonic
      antigen (CEA) family which has been shown to be normally expressed at the apical
      pole of epithelial cells and to show a dysregulated expression pattern in tumors
      derived from the latter. The purpose of the present study was to investigate the
      expression pattern of CEACAM1 in gestational trophoblastic lesions and to compare
      this expression with the one observed in the normal trophoblast. For this
      purpose, we performed immunohistochemistry using the 4D1/C2 monoclonal antibody
      which specifically recognizes CEACAM1 and does not interact with other members of
      the CEA family. Immunohistochemistry was performed on a total of 20 cases of
      gestational trophoblastic lesions including complete hydatidiform moles, one
      placental site trophoblastic nodule (PSN), one placental site trophoblastic tumor
      (PSTT), and three choriocarcinomas. Immunostaining for cytokeratin, hPL, hCG, and
      Ki-67 was also performed. Normal placental samples served as a control. CEACAM1
      was absent from villous cyto- and syncytiotrophoblast in both normal placenta and
      hydatidiform molar samples. It was present in the benign extravillous
      trophoblast, with stronger expression in the proximal extravillous trophoblast of
      anchoring villi, but was also observed in interstitial and endovascular
      intermediate trophoblast and chorionic intermediate-like trophoblast. Partial
      expression was observed in the trophoblast proliferating from the surface of
      molar villi. In choriocarcinomas, areas of weak expression could be observed
      along with large areas without CEACAM1 expression. In the PSN and especially in
      the PSTT, CEACAM1 expression was stronger and more diffuse. The specific
      localization to extravillous trophoblast and its expression pattern in
      gestational trophoblastic lesions indicate that CEACAM1 can potentially be a
      helpful additional diagnostic marker in the differential diagnosis of such
      lesions.

PMID- 11293163
TI  - Transepithelial elimination of late cutaneous vulvar schistosomiasis.
AB  - Late cutaneous vulvar schistosomiasis (LCVS), which represents the cutaneous
      response to the deposition of schistosomal ova, is characterized by a range of
      clinical manifestations. Histopathological descriptions of LCVS have highlighted
      the hyperplastic epithelial reaction, and a few reports have alluded to the
      presence of intraepidermal bilharzial ova. Although transepithelial elimination
      (TEE), a well-known phenomenon whereby the skin rids itself of foreign,
      potentially dangerous substances, has been documented in a range of infectious
      processes, it has not been recognized as a distinct process in LCVS. This study
      not only documents TEE in 23 biopsies of LCVS but also correlates the role of the
      histopathological inflammatory reaction pattern, density of ova, and
      pseudoepitheliomatous hyperplasia in the pathogenesis of TEE. The importance of
      TEE as an additional, hitherto unrecognized mechanism of release and spread of
      schistosomal ova to the exterior is also highlighted.

PMID- 11293164
TI  - Utility of trichrome and reticulin stains in the diagnosis of superficial
      endometriosis of the uterine cervix.
AB  - Superficial endometriosis of the uterine cervix is a not uncommon lesion and the
      cells on the cervicovaginal smear shed from it can be easily mistaken for
      cervical glandular intraepithelial neoplasia (CGIN). The correct diagnosis can
      not always be easily made on H&E stained tissue sections unless it is suspected.
      The endometriotic stroma is often misinterpreted as stromal hypercellularity or
      postinflammatory fibrosis following erosion or ulceration of the cervical mucosa.
      Moreover, the endometriotic glands may resemble tubo-endometrioid metaplasia of
      the endocervical glands. This article describes the utility of trichrome and
      reticulin stains in the diagnosis of superficial cervical endometriosis. The
      absence of abundant thick collagen bundles and the investment of individual
      stromal cells by a fine reticulin network within the endometriotic foci are
      characteristic histologic features. These findings are not observed in the
      surrounding normal cervical stroma nor in the usual conditions in the
      differential diagnosis.

PMID- 11293165
TI  - Relationship between telomerase activation and HPV 16/18 oncogene expression in
      squamous intraepithelial lesions and squamous cell carcinomas of the uterine
      cervix.
AB  - SILs (squamous intraepithelial lesions) comprise a wide spectrum of clinically
      and biologically heterogeneous lesions ranging from benign proliferations to
      precancerous lesions. Telomerase activation plays a critical role in cellular
      immortalization and might be important for malignant progression. The viral
      oncogenes E6 and E7 are the principal transforming genes of high-risk HPVs and
      are important in HPV-associated immortalization and neoplastic transformation. In
      this study we investigated the relationship between telomerase activity,
      telomerase RNA, and HPV 16/18 oncogene expression in low- and high-grade SILs and
      SCCs (squamous cell carcinomas) of the cervix uteri. Telomerase activity was
      examined by the TRAP-assay and expression of the telomerase RNA (hTR) and HPV
      16/18 E6/E7 oncogenes by RNA/RNA-in situ hybridization (ISH). The associated HPV
      type was determined by PCR. Telomerase activity was observed in 25/29 (86%) SCCs,
      31/41 (76%) high-grade SILs, 6/14 (43%) low-grade SILs, and 1/28 (3.6%) normal
      cervical tissues. Expression of hTR and viral oncogenes increased significantly
      with histopathologic severity of the lesion (p < 0.0001). A correlation was found
      between telomerase activity and intensity of viral oncogene expression. These
      findings suggest that telomerase activation occurs early in cervical
      carcinogenesis and is predominantly found in high-grade SILs and cervical SCCs.
      Our findings support current experimental data that suggest that telomerase is at
      least partially activated by viral oncogenes of high-risk HPV types. Telomerase
      activity with concomitant strong viral oncogene expression might therefore
      characterize a subset of lesions that are at risk for malignant progression.

PMID- 11293166
TI  - Uterine carcinosarcoma with melanocytic differentiation.
AB  - A 65-year-old black woman was found to have a 3.0 cm endometrial tumor that was a
      carcinosarcoma with a major epithelial and a less prominent mesenchymal
      component. The latter was undifferentiated but one focus of chondroid
      differentiation was noted. The former showed papillary serous differentiation.
      Melanin pigment was observed in both epithelial and mesenchymal components.
      Staining with antisera to S100 protein and HMB-45 confirmed the presence of
      melanocytes. An endocervical focus of tumor also contained melanin. Electron
      microscopic studies showed large tumor cells with an irregularly indented nucleus
      and abnormal giant cytoplasmic melanosomes. Only one case of uterine
      carcinosarcoma with melanocytic differentiation has been previously reported.

PMID- 11293167
TI  - Primary mullerian carcinosarcoma of the retroperitoneum: report of a case.
AB  - A mullerian carcinosarcoma or malignant mesodermal mixed tumor (MMMT) originated
      from the retroperitoneum of a 51-year-old woman; only two previous similar cases
      have been reported. The 1,040 gm tumor was found in the left retroperitoneal
      space; the center of the tumor was extensively liquified. The uterus, fallopian
      tubes, and ovaries were unremarkable. The histopathological features of the tumor
      were typical of MMMT, homologous type. The adenocarcinomatous component of the
      tumor was immunohistochemically positive for cytokeratin 7 and negative for
      cytokeratin 20. MMMTs arising in extragenital sites are rare, and most of them
      arise from the peritoneum. The histogenesis of extragenital MMMTs remains
      speculative, but the origin from the "secondary mullerian system" is most likely.

PMID- 11293168
TI  - Androgen receptor gene mutation associated with complete androgen insensitivity
      syndrome and Sertoli cell adenoma.
AB  - We report a case of Sertoli cell adenoma in complete androgen insensitivity
      syndrome (CAIS) in a 22-year-old woman. Polymerase chain reaction-single strand
      conformation polymorphism and DNA sequencing revealed a single nucleotide
      substitution on exon 7 of the human androgen receptor (hAR) gene, resulting in a
      change of CGA (arginine) to CAA (glutamine) in codon 831.

PMID- 11293169
TI  - Cellular angiofibroma of the vulva with DNA ploidy analysis.
AB  - Cellular angiofibroma (CAF) is a recently described rare soft tissue neoplasm of
      the vulva (with only four reported cases) that typically occurs as a well
      circumscribed solid rubbery vulvar mass in middle-aged women. The distinct
      histologic features of bland spindle cells admixed with numerous hyalinized
      medium to small blood vessels, and a vimentin-positive desmin-negative
      immunoprofile differentiates this neoplasm from other vulvar tumors such as
      angiomyofibroblastoma and aggressive angiomyxoma. In this report an additional
      case of CAF is presented with DNA ploidy analysis and CD99 immunohistochemistry.

PMID- 11293170
TI  - Primary vaginal adenocarcinoma of intestinal type arising from an adenoma: case
      report and review of the literature.
AB  - A 1 cm polypoid lesion was encountered on the posterior vaginal wall in a 56-year
      old woman with no history of diethylstilbestrol exposure that on microscopic
      examination was a moderately differentiated adenocarcinoma of intestinal type.
      The tumor was cytokeratin 20 and carcinoembryonic antigen positive and negative
      for cytokeratin 7. Mucin histochemistry demonstrated the presence of o-acetylated
      sialomucin, a specific marker of large intestinal differentiation. The initial
      interpretation favored a metastasis from a colonic adenocarcinoma, but clinical
      investigations showed no evidence of a primary gastrointestinal lesion. The
      morphology, histochemical, and differential cytokeratin profile led to the lesion
      being reinterpreted as a primary intestinal-type adenocarcinoma of the vagina
      arising from a tubular adenoma. Although a very rare tumor, awareness of this
      lesion is important as it must be distinguished from metastatic adenocarcinomas
      from other sites.

PMID- 11293171
TI  - Risk stratification in patients with liver disease for surgery.

PMID- 11293172
TI  - Surgery in patients with liver disease: hematological management.

PMID- 11293173
TI  - Non-hepatic surgery in patients with chronic liver disease.

PMID- 11293174
TI  - Problems of hepatic surgery in patients with liver disease.

PMID- 11293175
TI  - Hepatobiliary and pancreatic ascariasis.
AB  - Ascariasis is a helminthic infection of global distribution with more than 1.4
      billion persons infected throughout the world. The majority of infections occur
      in the developing countries of Asia and Latin America. Of 4 million people
      infected in the United States, a large percentage are immigrants from developing
      countries. Ascaris-related clinical disease is restricted to subjects with heavy
      worm load, and an estimated 1.2 to 2 million such cases, with 20,000 deaths,
      occur in endemic areas per year. More often, recurring moderate infections cause
      stunting of linear growth, cause reduced cognitive function, and contribute to
      existing malnutrition in children in endemic areas. HPA is a frequent cause of
      biliary and pancreatic disease in endemic areas. It occurs in adult women and can
      cause biliary colic, acute cholecystitis, acute cholangitis, acute pancreatitis,
      and hepatic abscess. RPC causing hepatic duct calculi is possibly an aftermath of
      recurrent biliary invasion in such areas. Ultrasonography can detect worms in the
      biliary tract and pancreas and is a useful noninvasive technique for diagnosis
      and follow-up of such patients. ERCP can help diagnose biliary and pancreatic
      ascariasis, including ascaris in the duodenum. Also, ERCP can be used to extract
      worms from the biliary and pancreatic ducts when indicated. Pyrantel pamoate,
      mebendazole, albendazole and levamisole are effective drugs and can be used for
      mass therapy to control ascariasis in endemic areas.

PMID- 11293176
TI  - Management of amebic and pyogenic liver abscess.
AB  - The management of pyogenic liver abscess differs radically from that of amebic
      liver abscess. Medical management is the cornerstone of therapy in amebic liver
      abscess while early intervention in the form of surgical therapy or catheter
      drainage and parenteral antibiotics is the rule in pyogenic liver abscess. The
      prognosis of amebic abscess is much better than that of pyogenic abscess and
      usually a quick response to therapy is seen in amebic abscess.

PMID- 11293177
TI  - Liver in malaria.

PMID- 11293178
TI  - Hydatid disease.

PMID- 11293179
TI  - The liver in enteric fever and leptospirosis.

PMID- 11293180
TI  - Current and future treatment of hepatitis C.
AB  - Hepatitis C virus infection is a major health burden affecting an estimated 200
      million people worldwide. Chronic hepatitis C is one of the leading causes of
      cirrhosis and end-stage liver cirrhosis; thus effective therapies are required.
      For many years interferon-alpha has been the treatment of choice for patients
      with chronic hepatitis C infection. However, in only 10%-15% of patients is
      interferon-alpha monotherapy successful, leading to sustained virological
      response. A combination of interferon-alpha and ribavirin significantly enhanced
      sustained virological response rates to 40%. Strategies to further improve
      response rates include modification of the interferon dosing schedule with
      induction dosing and daily interferon, new interferons such as consensus
      interferon, or interferon with longer half-life and more favorable
      pharmacokinetics such as pegylated interferons. Recent trials showed that a
      combination of pegylated interferons and ribavirin leads to sustained response
      rates of about 50% with an acceptable safety profile. Hopefully, new treatment
      modalities will be available in the near future. Helicase, protease and the RNA
      polymerase are potential targets to suppress HCV replication and several
      immunotherapeutic approaches are explored.

PMID- 11293181
TI  - Management protocols for hepatitis B.

PMID- 11293182
TI  - Role of vaccination and adoptive immune transfer in persistent hepatitis B virus
      infection.

PMID- 11293183
TI  - Transplantation for chronic hepatitis B and C: strategies for prevention and
      treatment of recurrent disease.

PMID- 11293184
TI  - Nonalcoholic steatohepatitis.

PMID- 11293185
TI  - Wilson disease.

PMID- 11293186
TI  - Pathophysiology of cholestasis.

PMID- 11293187
TI  - A primer on the pathology of cholestasis.

PMID- 11293188
TI  - Clinical spectrum of cholestasis.

PMID- 11293189
TI  - Treatment of cholestasis and cholestatic disorders.
AB  - The future of therapy of chronic cholestatic disorders is bright given the large
      number of new drugs that are in the initial phases of study. UDCA is currently
      the mainstay of therapy.

PMID- 11293190
TI  - Treatment of hepatic encephalopathy.

PMID- 11293191
TI  - Increasing incidence of hepatocellular carcinoma associated with hepatitis C
      virus infection in Japan.

PMID- 11293192
TI  - Management of variceal bleeding.

PMID- 11293193
TI  - A descriptive study of hypertension in Vietnamese Americans.
AB  - This study focused on the extent of hypertension (HTN) and risk factors in 201
      Vietnamese in a Gulf Coast community. Blood pressure and pulse were measured by a
      Welch-Allyn Vital Signs Monitor (Model AD-9000, Armstrong Medical, Lincolnshire,
      IL). The survey tool consisted of demographic information, health status,
      medications, dietary habits, smoking and alcohol use, education, family
      configuration, family health history, and 12 true or false items on HTN
      knowledge. Participants believed that HTN was inherited, presented symptoms, was
      caused by stress and lack of daily exercise, and had no cure. Of the factors
      correlated with high blood pressure, the most significant item was the total
      knowledge score. Nearly 44% of the participants in this sample were hypertensive.
      Other significant correlation findings included smoking r = .45, p < .05) and
      exercise r = .15, p < .05) were related to high blood pressure. Cultural
      sensitivity was found to be critical in the data collection process. This study
      demonstrates a profound need for health education related to cardiovascular
      disease, smoking, and alcohol use in Vietnamese Americans.

PMID- 11293194
TI  - Parish nurses influencing determinants of health.
AB  - How are the concepts health, health promotion, faith community, and health
      determinants connected? How can a nurse draw on the unique features of a faith
      community to promote health? In this article, we explore the relations among
      these concepts and consider the answers to these questions. Parish nurses provide
      a concrete example of the interactions among these concepts. They are often hired
      by faith communities to intentionally promote health within and beyond the faith
      community. Increasingly, faith communities are being used as settings for health
      promotion interventions. We describe examples of how a parish nurse can influence
      2 determinants of health: social support and healthy child development.

PMID- 11293195
TI  - Homeless women and children's access to health care: a paradox.
AB  - Homeless women and children who reside in shelters experience many health-related
      problems. The aim of the qualitative study reported here was to (a) explore how
      shelter staffs manage health problems among their residents and assist them in
      accessing health services, and (b) identify clinical strategies for community
      health nurses working with this population. Findings demonstrate a paradox
      whereby homeless shelter staffs try to gain access to care for their residents
      through a system that is designed to keep them out. In addition, findings
      indicate a need for increased community health nursing services in homeless
      shelters. Strategies for resolving this paradox include providing assessment,
      policy development, and assurance of health care for homeless women and children.

PMID- 11293196
TI  - Meeting health care needs of a vulnerable population: perceived barriers.
AB  - This study utilized the qualitative methodology of focus groups to explore health
      care needs and perceived barriers to obtaining health care for urban and rural
      women and children in areas served by nurse practitioner (NP) and certified nurse
      midwife (CNM) clinics. The clinics operate in a southeastern county with a rural
      health professional shortage area designation, and an urban ZIP code area with
      high rates of infant mortality and serious pediatric conditions. The aim of the
      study was to delineate barriers to health care in order to develop appropriate
      services at the clinics and to improve access. Four focus groups with a total of
      31 women from the communities were convened. Content analysis shows that access
      to the clinics is hampered by the community women's limited knowledge of CNMs and
      NPs and their specific roles in providing health care services. The women
      suggested that clinics counter their low profile by a more vigorous outreach
      promotion.

PMID- 11293197
TI  - Health of America's newcomers.
AB  - Newcomer health and health care are policy issues with major outcomes of cost
      shifting and enormous consequences for newcomers and the community health nurses
      who promise them care. Newcomers are persons entering U.S. borders who could be
      asylees, refugees, immigrants, legal or illegal aliens, migrants, international
      adoptees, and others. Described in this article are the role federalism has
      played on the interplay among policymakers regarding newcomer health. Also
      addressed is newcomer health policy, including immigration policies, and newcomer
      health issues such as infectious diseases and questionable health care.
      Additional newcomer health issues such as newcomers at high risk for health
      problems, issues of access to care for newcomers, and welfare reform policies are
      discussed. Newcomer health and special interest group activities such as those
      from medicine and nursing are also addressed. Finally, meaningful options and
      possible solutions for newcomer health care concerns are identified and shared.

PMID- 11293198
TI  - Older adult patients with both psychiatric and substance abuse disorders:
      prevalence and health service use.
AB  - The prevalence and service use among older adults with concurrent psychiatric and
      substance abuse disorders (the "dually diagnosed") was examined in a cross
      sectional survey of a representative national sample of Department of Veterans
      Affairs mental health program patients (N = 91,752). Rates of dual diagnosis
      declined significantly (P = 0.001) as the age of the respondents increased (26.7%
      of patients < 65 years; 6.9% of patients > or = 65 years). Dually diagnosed older
      adult patients had longer inpatient stays for substance abuse and more outpatient
      substance abuse visits than did non-dually diagnosed elderly patients, and more
      outpatient general psychiatric visits than all the contrast groups. Dual
      diagnosis appears less common among older compared to younger patients, although
      their heavy use of certain (particularly, outpatient psychiatric) services
      suggests that should more dually diagnosed patients survive to old age their
      consumption of some forms of mental health care is likely to be high.

PMID- 11293199
TI  - Nonviolent psychiatric inpatients and subsequent assaults on community patients
      and staff.
AB  - Health care staff on psychiatric inpatient units are at high risk for work
      related assaults by patients. Recent studies have begun to document similar
      patient assaults toward staff in community-based residences. Earlier community
      studies did not control for the level of patient assault prior to community
      discharge, and it remains unknown whether the community residence assaults were a
      function of community placement or a reflection of ongoing control issues by the
      recently discharged patients. This preliminary inquiry retrospectively tracked
      the nature and frequency of assaults by patients newly discharged to community
      residences from a state hospital setting where there had been no assaults by
      these patients for a two-and-one half-year period. While base rates remain to be
      determined, the findings in this study suggest the assaultive patients to be
      younger males with diagnoses of schizophrenia and histories of violence toward
      others, substance abuse, and violence toward self. Nine patients committed the
      majority of the assaults. There was a significant decline in the frequency of
      assaults nine months post-discharge. The implications are discussed.

PMID- 11293200
TI  - Clinical characteristics of older psychiatric inpatients with borderline
      personality disorder.
AB  - This case study investigation considers typical and potentially unique
      characteristics of older (> 50 years) Borderline Personality Disorder (BPD)
      patients and describes their impact on an inpatient psychiatric unit encompassing
      a therapeutic milieu setting and multidisciplinary treatment teams. The
      somatization of symptoms, in particular, and the associated therapeutic, medical,
      and psychopharmacological interventions, result in prolonged and elaborate
      treatments that undermine clinical and personal boundaries, clash with managed
      care directives, and engender frustrating and elusive transferential and
      countertransferential reactions. Moreover, the guilt-inducing nature of
      somatization and physical frailty in older individuals, combined with the well
      documented ability of BPD patients, regardless of age, to incite stormy and
      'split' relationships, are linked characteristics that may describe a diagnostic
      subtype of BPD. Rather than suggesting a diminution of psychopathology as BPD
      patients age, the results of this investigation indicate that their persistent
      difficulties may only be altering in content and in pathological adaptation to
      changing needs.

PMID- 11293201
TI  - The last mental hospital.
AB  - The public mental hospital system was created in part because many mentally ill
      people were being held in prisons and jails. Support for those hospitals waned
      over time, however, and by the time they had degenerated into "snake pits" a
      consensus was reached to close them down. Unfortunately, they were not replaced
      with adequate community mental health resources, so as the hospitals have
      emptied, the prisons and jails have filled, partly with the mentally ill. That is
      the destructive reason for the growth of prison psychiatry in this country: the
      prison has become the last mental hospital. The constructive one has been a new
      emphasis on bringing psychiatric treatment to a previously neglected population:
      people who have committed serious violence, whether because of Axis I mental
      illnesses or Axis II character disorders. Unfortunately, four inter-related,
      mutually reinforcing nationwide trends threaten to reinforce that destructive
      development and vitiate the constructive one.

PMID- 11293202
TI  - The mentally ill in jails and prisons: towards an integrated model of prevention.
AB  - Jails and prisons have become a final destination for persons with severe mental
      illness in America. Addiction, homelessness, and fragmentation of services have
      contributed to the problem, and have underscored the need for new models of
      service delivery. Project Link is a university-led consortium of five community
      agencies in Monroe County, New York that spans healthcare, social service and
      criminal justice systems. The program features a mobile treatment team with a
      forensic psychiatrist, a dual diagnosis treatment residence, and culturally
      competent staff. This paper discusses the importance of service integration in
      preventing jail and hospital recidivism, and describes steps that Project Link
      has taken towards integrating healthcare, criminal justice, and social services.
      Results from a preliminary evaluation suggest that Project Link may be effective
      in reducing recidivism and in improving community adjustment among severely
      mentally ill patients with histories of arrest and incarceration.

PMID- 11293203
TI  - Knowledge transfer, policymaking and community empowerment: a consensus model
      approach for providing public mental health and substance abuse services.
AB  - An important problem in creating new programs and policies is how to encourage
      the transfer of knowledge in non-hierarchical ways so that new, relevant and
      specific knowledge is co-created by all interested parties. In this paper, we
      suggest that a consensus model of policymaking is one response and identify four
      key structural elements thought necessary for creating such a consensus
      infrastructure. These are a) a leadership and facilitating capacity for
      initiating and promoting such an endeavor, b) a network or consortium of key
      researchers, practitioners, consumers, and policymakers to empower community
      ownership of the endeavor, c) a process for consensus building and strategic
      problem-solving for such a consortium, and d) the continued creation of a multi
      directional dialogue through information dissemination. We examine these elements
      in action by describing a particular problem solving and consensus building model
      for developing and implementing a program, resolving group differences, and
      evaluating the group's process and products.

PMID- 11293204
TI  - [Principles of managing Helicobacter pylori infections. Guidelines of the
      European Society of Gastroenterology in Primary Health Care].

PMID- 11293205
TI  - [Seasonal variation and influence of atmospheric pressure diurnal fluctuations on
      occurrence of acute complications in patients with stomach and duodenal ulcer].
AB  - Although there is rich literature concerning seasonal fluctuations of incidence
      of peptic ulcer, no one can find so many data on acute complications of this
      disease--bleedings and perforations. There is also only little information saying
      about the role of meteorological factors that can take part in occurrence of the
      mentioned complications. This study aimed to analyze the seasonal variation (in
      calendar months, quarters of the year and calendar seasons--winter, spring,
      summer, autumn) of peptic ulcer bleeding and perforations as well as the
      influence of atmospheric pressure diurnal fluctuations on the occurrence of these
      diseases. The conducted study was retrospective and based on data of patients
      admitted to III Department of General Surgery of the Jagiellonian University
      Medical School in Cracow. Altogether, from 1993 to 1997--26 patients with peptic
      gastroduodenal ulcer bleeding were admitted. 220 bleedings were endoscopically
      proven (6 patients did not agree for gastroscopy and were excluded from further
      analysis). 157 patients were treated because of peptic ulcer perforation at the
      same time and all of them underwent surgical procedure during which perforation
      was proven. The chi 2 test was used in order to verify our statistic hypothesis
      (p = 0.05). The examination did not show any significant seasonal variation of
      the studied complications. Neither hemorrhage nor perforation presented any
      seasonal prevalence. As for calendar months, quarters and calendar seasons (p >
      0.01; p > 0.02; p > 0.02 respectively). However, the study confirmed the role of
      atmospheric pressure falls in the occurrence of both: bleeding and perforation of
      peptic ulcer (p < 0.001). 153 patients with bleeding were admitted on days with
      decreasing pressure, while 67 when pressure was going up. Similarly as for
      perforations--94 with falling down to 33 with growing up pressure.

PMID- 11293206
TI  - [Surgical treatment of neoplastic obstruction of the left colon--economic and
      medical aspects].
AB  - Left-sided obstructing resectable colonic cancer is treated by one-stage
      resection-anastomosis or resection without anastomosis (the Hartmann operation).
      Morbidity and mortality rates after the first and the second procedure performed
      in our Department were similar, therefore we analyzed the duration of the
      operation, hospital stay, cost of the operation, and yearly cost of management.
      In one-stage operation, the operating time was longer and the costs higher than
      in the Hartmann procedure. One-stage procedure stay in surgical department was
      shorter, quality of life higher, and finally, year expenses--cheaper.

PMID- 11293207
TI  - [Incidence of chronic obstructive pulmonary disease among chronic smokers
      inhabiting Krakow and Proszowice].
AB  - COPD is the most common chronic lung condition whose identification is delayed.
      This paper undertakes to identify the present COPD occurrence frequency in the
      urban area of Krakow and the rural area of Proszowice. It makes use of free of
      charge spirometry tests in > 40 year-old volunteers, with the smoking history of
      at least 1 pack of cigarettes per day for 10 years. One in four persons examined
      in Krakow and one in three persons examined in Proszowice manifested ventilation
      impairment mainly of the obturation type. Severe obturation was diagnosed in one
      in three persons with ventilation dysfunction. In the conclusion the vital
      influence of COPD on public health is stressed, which should prompt a serious
      programme of early COPD identification and treatment, on regional or national
      scale.

PMID- 11293208
TI  - [Results of kidney transplantation in Krakow in 1992-2000].
AB  - The aim of the study was an analysis of renal transplantation results in the
      Krakow Transplant Center during 1992-2000. The analysis concerned 94 cadaveric
      transplant recipients. The study group included 31 females aged 23 to 61 years
      (mean 40.4 years) and 63 males aged 16 to 60 years (mean 41.8 years). The time of
      pre-transplant renal replacement therapy ranged from 4 to 120 months (mean 32
      months). The mean time of total ischaemia was 22 hours 20 minutes. The majority
      of the recipients had three identical antigens out of six typed. Most of the
      recipients were treated with three immunosuppressive drugs including:
      Cyclosporine A, Azathioprine and steroids. Immediately after kidney
      transplantation 25.6% of the patients had urine output and did not require
      dialysis. Acute renal failure (ARF) of the graft was observed in 73.2%
      recipients. The average number of hemodialysis sessions in patients presenting
      ARF was 10. Acute rejection was diagnosed in 41.5% of the patients. The most
      frequent complications were: CMV (cytomegalovirus) infection, UTI (urinary tract
      infection) and policytemia. In the study group 1-year survival rate of the
      patients was 97.8% and 1-year graft survival was 93.61%. The 5-year survival
      rates both in the patients and the grafts were very satisfactory (96.96% and
      87.7% respectively).

PMID- 11293209
TI  - [Cyclophosphamide pulse therapy in patients with primary glomerulonephritis].
AB  - Cyclophosphamide is a cytostatic drug, widely used in therapy of secondary
      glomerulonephritis. Because pulse therapy bears less side effects than oral one
      we aimed to follow the cyclophosphamide effect on the course of patients with
      primary glomerulonephritis. We observed 20 pts (7 women and 13 men), mean age 33
      +/- 10.0 yrs, age range 18-50 yrs with primary glomerulonephritis and proteinuria
      more than 3.5 g. 12 patients also had erythro-cyturia. In all pts kidney biopsy
      was performed, but in one woman the biopsy was not diagnostic. Renal biopsy
      revealed: FSG in 2 pts, membranous glomerulonephritis in 2 pts, in 9 pts
      mesangial proliferative changes and in 6--mesangiocapillary lesions. In 5 pts
      renal failure was observed. Cyclophosphamide was administered i.v. in the dose
      0.75 g/m2 b.s., no more than 1.0 g per dose, in renal failure 0.5 g/m2. During
      the first six months patients received cyclophosphamide every month and then
      every three months. Before cyclophosphamide pulse therapy all patients were
      pretreated with steroids, 3 pulses of 1.0 g Methylprednisolone and then oral
      prednisone in the dose 20 mg/m2 body surface. RESULTS: In 3 patients we obtained
      remission of proteinuria, in 11 patients decrease of proteinuria but 6 patients
      didn't answer to the introduced treatment. In whole group of examined patients we
      obtained the statistically significant decrease of proteinuria from 12.2 +/- 10.5
      to 5.3 +/- 5.2 g (p < 0.05) after the treatment. The creatinine clearance did not
      change in the time of the treatment and any special complications during the
      treatment were observed. We suggest that cyclophosphamide pulse therapy could be
      an effective treatment in pts with primary glomerulonephritis. Our results showed
      that the answer of proposed treatment was independent of the type to the changes
      found in kidney biopsy.

PMID- 11293210
TI  - [Comparison of anti-HBV vaccine efficacy given intradermally and intramuscularly
      in hemodialysis patients].
AB  - Patients chronically hemodialysed are recognised as a group of especially high
      risk for viral hepatitis B (HBV) infection. Moreover, their hyporesponsiveness to
      vaccination is widely known. So establishment of highly effective vaccination
      protocol is indispensable. We are presenting 5 year prospective observations of
      results of hemodialysis patients anti-HBV vaccination. 36 patients were
      vaccinated intramuscularly (among them 30 were revaccinated intradermally) and 40
      patients--only intradermally. We revealed that seroprotective level of anti-HBs
      antibodies should be at least 100 IU/ml. We disclosed, that intradermal anti-HBV
      vaccination--compared to intramuscular--was significantly more effective (77.5%-
      and including answer in the second vaccination cycle 85.0%--vs 38.9%) and,
      moreover, less amount of vaccine could be used (28.2 micrograms--and for patients
      answering barely in the second vaccination cycle 53.7 micrograms--vs 123
      micrograms). However, after intradermal vaccination seroprotective antibodies
      level falls faster and should be checked every 3 months. Patients answering
      efficiently to vaccination--comparing to answering inefficiently--have
      significantly higher albumin level and are younger. Moreover, higher dialysis
      dose favors the successful long-time answer to vaccination.

PMID- 11293211
TI  - [The effect of myocardial revascularization on global and regional systolic and
      diastolic left and right ventricular function].
AB  - The objective of the study was to evaluate the effect of myocardial
      revascularization (PTCA, CABG) on right and left ventricular systolic and
      diastolic function, and segmental wall motion in patients with coronary artery
      disease. The study population consisted of 27 patients, ranging in age from 36 to
      67 years (mean age 51.1 +/- 8.8). CABG and PTCA were performed in 17 and 10
      patients, respectively. All patients underwent radionuclide angiocardiography at
      baseline and 3 months after the procedure. The following parameters were
      measured: ejection fraction (EF), 1/3EF, maximal emptying rate (MER), maximal
      filling rate (MFR), 1/3 filling fraction (1/3FF), and segmental wall motion in
      segments S1 to S9. Increased left ventricular EF was observed in 29.4% of
      patients after CABG and in 40% of patients after PTCA. Segmental wall motion in
      the revascularized area also improved except for septal segments in the left
      ventricle in patients after CABG. Global right ventricular function remained
      practically unchanged both after CABG and PTCA. However, EF of right ventricular
      septal segments increased after CABG: S1--24.58 +/- 11.7% vs 33.4 +/- 14.7%, S9-
      35.52 +/- 13.7% vs 46.8 +/- 15.9%. CONCLUSION: Myocardial revascularization
      improves left ventricular systolic and diastolic function with no effect on
      global right ventricular performance. After CABG the ejection fraction of septal
      segments was altered. Successful PTCA of LAD improves EF of septal segments in
      the left ventricle.

PMID- 11293213
TI  - [Cardura XL--a unique drug formulation--doxazosine administered in a slow-release
      form (doxazosine GITS)].
AB  - An active component in the tablet Cardura XL is doxazosine. Doxazosine belongs to
      the third generation of alpha 1-adrenolytics. It is a blocker of post-synaptic
      alpha 1-receptors both in humans and in animals. It is a long acting preparation.
      A tablet cover of Cardura XL is built of two layers (GITS system). It has enabled
      administration of doxazosine once a day. A great advance of the GITS system is a
      verly slow and systematic release of the drug from the tablet. This release is
      independent of pH of gastro-intestinal content or peristalsis. After
      administration of the tablet of Cardura XL, over 85% of the drug is released
      after 12 hours and the release ends after 12-16 hours. Maximal serum drug level
      after administration of doxazosine GITS is observed after 14-16 hours. Higher
      maximal serum drug level is achieved when the drug is administered together with
      a meal. Using doxazosine in the GITS form, minimal and maximal serum drug levels
      during the whole 24 hours differ non significantly. GITS technology enabled
      achieving stable daily serum drug concentration. Introducing doxazosine GITS
      caused: 1. decrease of Cmax; 2. elongation of Tmax; and 3. decrease of Cmin
      compared to doxazosine. It became possible due to gradual absorption of the
      preparation from gastrointestinal tract and improved coefficient of the drug
      fluctuation. It should be stated that the described pharmacological differences
      of doxazosine GITS in younger and elderly, in female and male patients do not
      influence significantly initial dosing of the drug. Stenosis of the
      gastrointestinal tract or chronic diarrhea affecting bowel passage of the drug,
      change its therapeutic effect. An effect of doxazosine GITS, doxazosine and
      placebo on blood pressure was studied in 392 patients with mild and moderate
      hypertension (< or = 220/95-115 mm Hg). Doxazosine GITS similarly to doxazosine
      effectively decreases blood pressure. The value of diastolic blood pressure
      decrease increases together with the therapy duration. Use of the unique GITS
      technology assures stable daily serum drug concentration. It results in: mild but
      permanent decrease of the blood pressure, decreased risk of side-effects,
      including orthostatic hypotony. Based on the performed post-registration studies
      it should be stated that doxazosine GITS is not only a very effective but also a
      safe preparation, which may be administered once daily. The treatment should be
      initialized with a dose of 4 mg daily. In as much as 60% of the patients with
      mild or moderate arterial hypertension, an initial dose (4 mg of Cardura XL)
      effectively lowers blood pressure. Taking into consideration unique features of
      the described preparation, it is worth thinking of Cardura XL while initializing
      or switching therapy in hypertensive patients. Cardura XL, due to favourable
      metabolic effects as well as the unique GITS technology seems to be the drug
      particularly suitable in hypertensive patients with accompanying dyslipidaemia,
      diabetes mellitus type 2 and/or benign prostata hypertrophy.

PMID- 11293212
TI  - [Evaluation of the relationship between the occurrence of headache, use of
      analgesics and realizing a therapeutic effect among patients with hypertension].
AB  - The aim of the study was to assess the prevalence of headaches and analgesic use
      in hypertensive patients and to evaluate the relationship between taking
      analgesic drugs and adherence to antihypertensive therapy. 754 consecutive
      hypertensive patients (446 women and 308 men, aged 18-89 years, median age--58
      years) from 7 out-patient centres participated in the study. Anonymous
      questionnaires consisted of 13 simple questions concerning demographic parameters
      (age, gender), clinical data (the duration of hypertension and antihypertensive
      therapy), the history of headache and use of analgesics were distributed among
      the participants. Among the hypertensives participating in the study, 82.9% (625)
      reported headaches. Analgesics were used by 65.3% (408) of hypertensive patients
      with headaches. There was significant, positive linear correlation between the
      history of headaches and the duration of analgesic use in hypertensive patients.
      The rate of non-compliance was significantly higher among patients with headaches
      who reported regular use of analgesics when compared to non-users of analgesics.
      There were statistically more non-compliants among patients taking more than 1
      type of analgesics than in hypertensives reporting use of only 1 analgesic drug.
      The prevalence of headaches and the rate of analgesic use is considerably
      significant among hypertensive patients. Analgesic consumption seems to be a risk
      factor for non-adherence to antihypertensive medication.

PMID- 11293215
TI  - [Sarcoidosis--a diagnostic and therapeutic problem].
AB  - Sarcoidosis is a multi-organ granulomatous disorder of an unknown cause. Skin
      sarcoidosis occurs in about 20-35% of patients with systemic disease and may also
      arise in isolation. A wide range of clinical presentations of cutaneous
      sarcoidosis is recognised. The diagnosis rests on the presence of non-caseating
      granulomas on skin biopsy. Treatment and overall prognosis of cutaneous
      sarcoidosis is primarily dependent on the degree of systemic involvement.

PMID- 11293214
TI  - [Stanols--a new perspective in treatment of hypercholesterolemia?].
AB  - Since the unfavorable impact of hypercholesterolemia on the cardiovascular system
      has been proven, effective, inexpensive and easy to use cholesterol-lowering
      treatment options have been looked for. In the 1990s as the effect of a few
      decades of research, stanols have been introduced as new cholesterol-lowering
      agents. Stanols are derivates of plant sterols, which act through inhibition of
      intestinal cholesterol absorption. Their incorporation into normal diet fats has
      led to a significant reduction of both total and LDL cholesterol in investigated
      subjects, also in those on cholesterol-lowering diet or taking cholesterol
      lowering drugs. When the dose considered optimal, i.e. 2-3 g/d, was used, the
      average reduction was 10% for total and 14% for LDL cholesterol. So far no
      adverse effects of stanols and no influence on the taste of food have been
      observed. The possible role of stanols in primary and secondary prevention of
      cardiovascular diseases still remains to be verified. It seems, however, that
      stanols have a potential to become a significant element in the treatment of
      hypercholesterolemia and in preventing its consequences.

PMID- 11293216
TI  - [Aluminum--occurrence and toxicity for organisms].
AB  - Aluminium (Al.) is an ubiquitous element found in every food product. The sources
      of Al. are especially corn, yellow cheese, salt, herbs, spices, tea and tap
      water. In household Al.-made ware is a major source of the element. Al. may cause
      diseases in humans, especially hampers many metabolic processes especially
      turnover of calcium, phosphorus and iron. Salts of Al. may bind to DNA, RNA,
      inhibit such enzymes as hexokinase, acid and alkaline phosphatases,
      phosphodiesterase and phosphooxydase. Al. salts are especially harmful to
      nervous, hematopoietic systems and to skeleton. Al. gets to organism with food,
      water, cosmetics, from aluminium ware and containers. Toxicity comes from
      substitution of Mg and Fe ions effecting in disturbances in intracellular
      signaling, excretory functions and cellular growth. Neurotoxic action of Al.
      probably comes from substitution of Mg ions in ATP, what finally influences
      function of every ATP using-enzymes. There are observations in experimental
      models proving Al. salts are responsible for Alzheimer disease development.
      Toxicity of Al. to skeletal system results in diminished resistance thus
      tendencies to breaking, and comes from lower collagen synthesis and slowing down
      of mineralisation. Low erythropoietin production, inhibition of hem-synthesing
      enzymes and binding of Al. to transferrin, effects in anaemia. Carcinogenic
      effects of Al. were nor proved nor denied, but high concentrations of Al. were
      found in many neoplastic cells. In conclusion, we should introduce prophylactic
      measures effecting in less Al. intake esp. avoiding use of Al.-made ware nad
      controlling food for Al. content.

PMID- 11293217
TI  - [Liver failure during the course of treatment of patients with bleeding
      esophageal varices].
AB  - Based on the bibliography and 30 years of experience, we present a current
      opinion on the treatment of patients with increasing liver failure in the course
      of the treatment of patients with bleeding esophageal varices.

PMID- 11293218
TI  - [Hematologic syndromes in hepatitis C virus infection].
AB  - HCV infection may affect not only the liver but also various nonhepatic tissues.
      This paper presents current information on association between HCV infection and
      haematological disorders. The pathogenic role of HCV in hepatitis-associated
      aplastic anaemia development has not been confirmed. The thrombocytopenia has
      been observed more frequently during chronic hepatitis C than during infections
      with other hepatotropic viruses. This disorder may be associated with
      antiplatelet autoantibodies production. However the most common haematological
      complication of HCV infection is mixed cryoglobulinemia (MC), observed in 40-50%
      of patients. In some subjects non-Hodgkin B cell lymphoma (B-NHL) may evolve from
      MC, but it is also reported in acryoglobulinemic HCV infected patients. The
      frequency of HCV infection in population of patients with B-NHL exceeds 20% in
      some countries and it is significantly higher than for other lymphoproliferative
      disorders. There are also data suggesting that HCV may play a role in MALT
      lymphoma development, too. The observed disorders are explained by HCV
      lymphotropism and direct or indirect influence of continuous antigenic
      stimulation by replicating virus on lymphatic system. The paper presents also
      beneficial results of interferon treatment in patients with HCV-related MC or B
      NHL. The authors show that haematological syndromes should be taken under account
      in diagnostics of hepatitis C patients and interferon treatment should be
      administered as soon as possible when HCV related cryoglobulinaemia is diagnosed.

PMID- 11293220
TI  - [Gastric neurofibroma--still a diagnostic problem].
AB  - We report a case of gastric neurofibroma encountered in 41-year-old woman who
      complained of dyspepsia and physical examination revealed palpable mass in her
      abdomen. It was not possible to determine the nature and origin of the tumor by
      radiological and endoscopic investigations. At laparotomy the tumor was found to
      be pendiculated and growing extramurally from the anterior wall of the stomach.
      Wedge gastric resection, including the mass, was performed. Histological
      examination revealed a spindle cell gastric tumor, immunohistochemically
      differentiated as a neurofibroma.

PMID- 11293219
TI  - [Practical use of anti-HB immunoglobulins].
AB  - Viral hepatitis B remains a significant problem among iatrogenic infections. The
      development of transplantology met a barrier in the form of active hepatitis B.
      Wide but still inadequate prophylaxis against viral hepatitis B and the necessity
      of protection of patients after organ transplantation against secondary HBV
      infection require establishing indications for specific, passive immunotherapy.

PMID- 11293221
TI  - [Selected aspects of rehabilitation programs for hemodialyzed patients in the
      United States ].
AB  - The purpose of the paper was to evaluate some aspects of U.S. rehabilitation
      programs, and medical health systems legislatives initiatives in the patients
      with end-stage renal diseases treated with hemodialysis. We signalized potential
      problems, and complications of rehabilitation in such group of patients. The
      potential improvement in quality of life after intradialysis, and interdialysis
      rehabilitation was discussed.

PMID- 11293222
TI  - [Comparison of principles for establishing disability pension eligibility for
      orthopedic cases used in Germany and in Poland. I. German rules for establishing
      eligibility in orthopedics].
AB  - The aim of the present paper is to compare the rules used in Germany and Poland
      to establish an individual's eligibility for a disability pension in cases of
      orthopedic disorders. Harmonizing these rules is one of the basic factors needed
      to create the proper platform for cooperation among health care systems in all
      the countries associated with the European Union. This first part of the work
      discusses the German rules for eligibility proceedings in orthopedic cases. The
      example of spinal disorders is used to explain the scheme of the examination
      conducted by the specialist to determine the disability group to which the person
      should belong. Attention is drawn to the rules governing the use of additional
      tests and eligibility proceedings.

PMID- 11293223
TI  - [Comparison of principles used to establish eligibility for disability pensions
      for orthopedic cases in Germany and in Poland. II. Polish rules for establishing
      eligibility in orthopedics].
AB  - The goal of the present paper is to compare the rules used in Germany and Poland
      to establish an individual's eligibility for a disability pension in cases of
      orthopedic disorders. Harmonizing these rules is one of the basic factors needed
      to create the proper platform for cooperation among health care systems in all
      the countries associated with the European Union. This second part of the work
      will discuss the Polish rules for eligibility proceedings in orthopedic cases.
      The example of spinal disorders is used to explain the format for the examination
      conducted by an orthopedic specialist in the course of the process of determining
      the disability group to which the person belongs.

PMID- 11293224
TI  - [The role of sulphonylurea derivatives in treatment of diabetes type 2. The role
      of glimepiride].
AB  - Type 2 diabetes is characterised by some kind of duality. In its pathogenesis an
      important role have as well genetic as environmental factors. Both of them
      influence the insulin secretion at the one side and the insulin resistance at the
      other one. Very important group of antidiabetic drugs are sulphonylureas. They
      bind to the sulphonylurea receptor localized at the potassium channel in the
      cellular membrane. Contemporary sulphonylurea derivatives should be characterised
      by rather weak binding with the receptor, action during mealtime only (prandial
      regulation of glycemia), not to strong insulin secretion and for the quality of
      life reason once daily application. This criteria are fulfilled by e.g. slow
      releasing preparations of glipizide and glikiazide and also by glimepiride.

PMID- 11293225
TI  - [Sulphonylurea derivatives and the cardiovascular system].
AB  - Sulphonylurea derivatives (SUD) are a mainstay of treatment of type 2 diabetes
      but questions have been raised about the potential adverse effects of these drugs
      as far as cardiovascular functions are concerned. An early prospective study
      which examined the effects of glycaemic control with various agents on coronary
      heart disease was stopped in the 70-ies due to excess cardiovascular mortality in
      the group receiving SUD of first generation: tolbutamide. The discovery of ATP
      sensitive potassium channels in the heart, their role in ischaemic heart disease
      and mechanisms of endogenous cardiac cell protection--preconditioning have
      brought back concerns of SUD safety. Recently, a new SUD--glimepiride--claimed as
      the first representant of III generation of these agents--has been introduced
      into clinical practice. Glimepiride appears to be devoid of vascular ATP
      sensitive potassium channels binding properties. Postulated and confirmed in
      animal experimental studies cardioprotective features of glimepiride were
      evaluated in a randomised, placebo-controlled study with glimepiride and
      glibenclamide comparing effects of these drugs on ischaemic preconditioning
      during angioplasty of high grade coronary artery stenoses in patients with stable
      angina. Myocardial ischaemia was quantified by intracoronary electrocardiography
      and time to occurrence of angina during vessel occlusion was measured. The
      results of the study confirmed glimepiride effects of maintaining myocardial
      preconditioning. The article summarises current knowledge of SUD influence on
      cardiovascular system and discusses some differences in pharmacodynamics of
      glimepiride which appear to provide this agent with clinical advantages over
      conventional SUD at least in cardiovascular aspects.

PMID- 11293226
TI  - [Evaluation of efficacy, safety and tolerance of glimepiride (Amaryl) in patients
      with type 2 diabetes].
AB  - Glimepiride is a new long-acting the third generation sulfonylurea given once
      daily. The aim of this study was to evaluate the efficacy, safety and
      tolerability of glimepiride given as monotherapy in type 2 diabetic patients. A
      total of 142 patients (65 women and 77 men; mean +/- SD: age 57 +/- 8.5 years,
      duration of diabetes 64.4 +/- 57.7 months, BMI 28.7 +/- 3.6 kg/m2) were treated
      during 12 weeks with glimepiride (Amaryl). Glimepiride was forced titrated 0.5
      7.0 mg once daily based on efficacy. Statistical analysis our results showed
      significant (p < 0.001) decrease of average fasting blood glucose, twenty-four
      hour plasma glucose values and HbA1c significantly lower. Systolic and diastolic
      blood pressure was also significantly (p < 0.001; p < 0.03) lower. There was a
      trend to lower serum cholesterol and triglyceride levels. The other laboratory
      values did not change during this study. No differences were registered in body
      weight. Safety was assessed by evaluating vital signs, laboratory values and the
      occurrence of adverse events. The frequency of hypoglycaemic events was very rare
      (0.7%). The percentage of patients with adverse drug reactions was 6.3%. The
      tolerance of glimepiride was good. CONCLUSION: This study demonstrates that
      glimepiride is effective, safe and well tolerated in improving glycaemic control
      in patients with type 2 diabetes.

PMID- 11293227
TI  - [Mortality from cardiovascular diseases in patients with type 2 diabetes].
AB  - In the period 1973/74-1995 a prospective observation was carried out on 4420
      diabetic patients (1990 males and 2430 females) aged 30-68 years, with type 2
      (non-insulin dependent diabetes) of 1-10 years duration. During the 22-year
      period nearly 80% of the initial cohort died. The risk of death was 2-times
      higher in diabetes than in the samples of general population observed at the same
      time. The death risk from cardiovascular diseases was over 3.0 times higher than
      in general population. The relevant risk ratio was found over 5-times higher for
      coronary heart disease, which was unlike to result from the differences in death
      ascertainment between diabetics and the city dwellers. The all-causes ratio of
      death and cardiovascular diseases was the same for women and men but it was
      selectively higher for females than males group for coronary heart disease and
      cerebrovascular diseases, and for males 50% higher for atherosclerosis and other
      heart diseases. The highest cumulation of risk factors was observed for deaths
      from cardiovascular diseases, and coronary heart disease. There were risk factors
      typical for cardiovascular disease and typical for poor metabolic control of
      diabetes (hyperglycaemia, glucosuria) and presence of complications of diabetes
      (nephropathy).

PMID- 11293228
TI  - [Diabetic cardiomyopathy. Pathophysiology and clinical implications].
AB  - The accumulating body of data indicate that the occurrence of diabetic
      cardiomyopathy is an independent phenomenon from macroangiographic changes in
      coronary arteries and hypertension. Results from animal studies, human
      histological results and clinical observations provided support for this
      phenomenon. Although the clinical symptoms have been identified, however, the
      pathogenesis of diabetic cardiomyopathy is uncertain. The definition of diabetic
      cardiomyopathy describes both specific defects in the myocytes from diabetics and
      associated changes in the heart which have developed during the course of
      diabetes. The following defects in myocytes have been identified and are
      postulated to contribute to diabetic cardiomyopathy: The changes in carbohydrates
      metabolism, in fatty-acid metabolism, calcium and potassium transport,
      microvascular narrowing and micro aneurysms, hypertrophy, defects in collagen
      structure, myocardial fibrosis and perivascular fibrosis, abnormalities in
      conducting system, the decrease in the function of autonomic nerves. The clinical
      presentation of diabetic cardiomyopathy lead to the description of two phases of
      the disease. First, asymptomatic diabetic subjects with subclinical abnormalities
      of the left-ventricular diastolic function, measured by Doppler echocardiography.
      In the second phase--clinically evident diabetic cardiomyopathy is described by
      congestive cardiac failure without evident arteriosclerotic changes in coronary
      arteries and hypertension. Diabetic cardiomyopathy can be diagnosed early after
      the onset of diabetes mellitus and is independent phenomenon from late diabetic
      complications. The main cause of mortality in diabetic subjects is largely due to
      macroangiopathic changes in the coronary arteries (evaluated by coronarography),
      not the heart failure.

PMID- 11293229
TI  - [Molecular background and clinical characteristics of autosomal dominant type 2
      diabetes mellitus].
AB  - Type 2 diabetes is a complex disease and genetic as well as environmental factors
      play a role in its pathogenesis. Six different genes have been identified so far
      to be responsible for rare forms of autosomal dominant, early onset type 2
      diabetes mellitus. All but one are transcription factors which influence
      expression of the other genes through the regulation of mRNA synthesis. These are
      hepatocyte nuclear factor (HNF)-4 alpha, HNF-1 alpha, insulin promoter factor
      (IPF)-1 and HNF-1 beta, which are associated with MODY1, 3, 4, 5 respectively.
      MODY1 is a relatively rare and usually severe form of diabetes. It is associated
      with progressive hyperglycemia and frequent chronic complications. The HNF-4
      alpha gene is localized on chromosome 20q. Similar clinical characteristics apply
      to the MODY3 form, however the latter is much more frequent among early onset,
      autosomal dominant type 2 diabetes (20-40%). HNF-1 alpha gene is localized on
      chromosome 12q. HNF-1 beta (MODY5 locus on chromosome 17q) is a protein which
      forms heterodimers with HNF-1 alpha. This rare form of diabetes has a clinical
      picture similar to MODY1 and MODY3. It is sometimes accompanied by symptoms of
      early kidney damage which are independent from diabetes. The other two
      transcription factors responsible for the development of autosomal dominant type
      2 diabetes are proteins which bind directly to the insulin promoter. MODY4 (IPF
      1, chromosome 13q) is a rare form and of a typical middle and late onset type 2
      diabetes. BETA 2/Neurod1 has been recently associated with MODY by Dr Krolewski's
      group from Joslin Diabetes Center, Boston, MA, USA. BETA 2 is responsible for
      about 2% of autosomal dominant type 2 diabetes. The clinical characteristics
      depend on the localization of the mutations in the specific functional domains of
      the protein. Mutations identified in the glucokinase gene are associated with the
      MODY2 form. Glucokinase is an enzyme involved in the first level of glucose
      metabolism in b-cells-enzymatic phosphorylation. MODY2 is a modest form of
      diabetes. It is characterized by mild hyper-glycemia, mainly fasting, and the
      chronic complications are very rare. Glucokinase gene is localized on chromosome
      7p. It is expected that in the nearest future more type 2 susceptibility genes
      will be identified.

PMID- 11293230
TI  - [Genetic factors with significance in pathogenesis of diabetic nephropathy--the
      role of polymorphism of renin-angiotensin system genes].
AB  - The article presents the contemporary view about the role of polymorphisms of
      renin-angiotensin system genes in the pathogenesis of diabetic nephropathy in
      subjects with type 1 and type 2 diabetes.

PMID- 11293231
TI  - [The role of genetic studies in finding the etiopathogenesis of diabetes
      mellitus].
AB  - The role of genetic investigations in diabetes one can describe in aspect of
      their role in the pathogenesis of type 1 and type 2 as well as in pathogenesis of
      chronic complications and gene therapy of diabetes. There is not only one gene
      responsible for type 1 diabetes. Similarly there are many gene-candidates in type
      2 diabetes. Only in 6 types of MODY the genes responsible for beta-cell
      dysfunction were described. In diabetic complications some role e.g. in
      retinopathy may be played by genes of growth factors, heparan sulfate synthesis
      as well as genes of adrenergic receptor beta 3. In diabetic nephropathy the genes
      of renin synthesis, converting enzyme, aldose reductase or angiotensin receptor
      can be of importance. It should be emphasized that identification of human genome
      and genes responsible for diabetes can contribute to introduction of gene therapy
      in diabetes.

PMID- 11293232
TI  - Methods for the study of the genetic determinants of diabetes and its
      complications.
AB  - Diabetes and its complications have a multifactorial etiology that includes both
      environmental and genetic factors. This makes the aim of finding susceptibility
      genes difficult because of the contribution of multiple genes, the wide variety
      of environmental factors that are involved, the lack of a clear mode of
      inheritance, and the presence of genetic heterogeneity. Despite these problems,
      the recent advances in biotechnology offer the opportunity to dissect the
      genetics background of complex diseases. As in the case of other disorders, there
      are two major approaches to study the molecular genetics of diabetes: association
      studies and linkage studies in families. Association studies aim to identify
      susceptibility alleles through several approaches, the simplest of which is to
      compare unrelated cases and controls. While this study design is relatively easy,
      false positive results are common due to unrecognized differences between cases
      and controls. An alternative is to use family-based association studies such as
      the transmission disequillibrium test. While this approach requires more
      recruitment efforts, the chances of false positive results are minimized. In
      contrast to association studies, linkage studies are not targeted to single
      candidate genes, but rather investigate the cosegregation between large
      chromosomal regions and the disease. Linkage analysis can be performed by either
      non-parametric or parametric methods. Non-parametric studies are relatively easy
      to conduct and do not require previous knowledge of the mode of inheritance.
      However, they cannot detect genetic heterogeneity (i.e. the presence of multiple
      genes that contribute to diabetes in different families). In contrast, parametric
      methods require large pedigrees and the assumption of a model of genetic
      inheritance, but they can detect genetic heterogeneity. Several new diabetes loci
      and genes have already been identified through the strategies outlined above, and
      many more are expected to be found in the next few years with the completion of
      the Human Genome Project.

PMID- 11293233
TI  - Decreased cytotoxicity and increased antimitotic activity of proline analogue of
      chlorambucil as a prodrug in breast cancer MCF-7 cells.

PMID- 11293234
TI  - alpha-asarone congeners as hypolipidemic agents. Pseudoreceptor versus
      minireceptor modeling.
AB  - The aim of our investigations was to construct activity models of alpha-asarone
      analogs and related compounds using in treatment of atherosclerosis. The models
      are based on pseudo- and minireceptor modeling. As a reference set of molecules
      20 alpha-asarone analogs were chosen. All of them were flexibly fitted to the
      four most probable alignments generated from the most active analogs. Subsequent
      analysis was conducted using pseudoreceptor module Receptor Surface Analysis from
      Cerius2 package. Statistical analysis based on Genetic Function Approximation
      revealed several QSAR models. Furthermore, minireceptor program PrGen was applied
      to the same alignments as above to evaluate atomistic receptor models against
      virtual particle pseudoreceptor models. Six new compounds with known activities
      but not included in the QSAR activity model building were used to test the
      created models.

PMID- 11293236
TI  - Molecular modelling of the interaction of carbocyclic analogues of netropsin and
      distamycin with d(CGCGAATTCGCG)2.

PMID- 11293235
TI  - Synthesis and immunomodulatory activity of novel analogues of human beta-casein
      fragment [54-59].
AB  - Three novel analogues of human beta-casein fragment [54-59] have been synthesized
      and tested for their immunomodulatory activity. Interestingly, human beta-casein
      fragment [54-59] has been found to be increased nitric oxide release from
      neutrophils. The obtained analogues have shown less immunomodulatory activity
      than native hexapeptide.

PMID- 11293237
TI  - Effect of pamidronate on skeletal morbidity in myelomatosis. Part 1. The results
      of the first 12 months of pamidronate therapy.
AB  - BACKGROUND: Osteolytic bone destruction caused by increase of osteolytic activity
      is a major manifestation of multiple myeloma (MM). Pamidronate (3-amino-1
      hydroxypropylidene)-1,1-bisphosphonate) inhibits osteoclastic activity and
      reduces bone resorption. METHODS: Since October 1995 the efficacy of pamidronate
      is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to
      VMCP/VBAP alternating regimen. 46 patients with stage III myeloma and osteolytic
      lesions were randomized to receive either pamidronate (Aredia; Novartis) 60 mg
      i.v. in 4-hour infusion monthly (n = 23) or chemotherapy alone (control group n =
      23). Estimation of performance status, quality of life, pain score, analgesic
      consumption, serum calcium concentration and twenty four-hours Calcium excretion,
      urine Calcium/creatinine ratio is done at least once a month (before pamidronate
      administration) while X-ray skeletal survey--before treatment and then every six
      months. RESULTS: In the first months of treatment apparent reduction of bone pain
      occurred. Hypercalcaemia was revealed in 6 patients at entry into the study. In 5
      of these patients pamidronate restored and maintained normocalcaemia for a median
      6 months. In 3 patients an aggressive plasma cell proliferation was accompanied
      by reoccurrence of hypercalcaemia. At skeletal X-ray examination performed after
      6 and 12 cycles of pamidronate and by comparing each of consecutive imaging with
      previous one the progression of osteolysis was respectively found in 67% and 39%
      of patients. In the control group corresponding figures were: 79% and 70%. The
      mean number of skeletal events (pathologic fracture, radiation to bone and spinal
      cord compression) per year was lower in the pamidronate group (1.82) than in
      control-patients (2.72), p < 0.013. The proportion of patients who developed
      skeletal event (excluding vertebral fractures) was lower in the pamidronate group
      -34% v 52%. Adverse events of pamidronate: hypocalcaemia (< 2 mmol/l) observed in
      7 patients occurred in particular patients beginning from 2 to 7 days after drug
      administration. In 2 patients hypocalcaemia that appeared in 24 hours after drug
      infusion was accompanied by blood pressure decrease; in one case systolic blood
      pressure dropped up to 60 mmHg, in the other one--to 90 mmHg. Muscular pain and
      fever up to 39 degrees C (transient and self-limiting "influenza like syndrom")
      occurred in 5 patients, in two patients after several hours and in three other-
      after some dozens of hours from drug administration. In one case
      hypertransaminasaemia was observed. CONCLUSIONS: In the first year of treatment
      monthly intravenous pamidronate administration as an adjunct to chemotherapy in
      patients with advanced multiple myeloma with osteolysis is an efficient approach
      in prevention and treatment of hyperacalcaemia, hypercalciuria and bone pain. It
      also shows some preventive effect on bone lesion occurrence.

PMID- 11293238
TI  - Antimicrobial activity of selected non-antibiotics--activity of methotrexate
      against Staphylococcus aureus strains.
AB  - Some non-antibiotic drugs, e.g. cytostatics, anaesthetics or vasodilators may
      also show the antimicrobial activity. The aim of this study was to detect and
      characterise the antimicrobial activity expressed by selected non-antibiotic
      drugs analysed during state control performed in the Drug Institute. Over 60
      drugs were randomly chosen from different groups. The surveillance study was
      performed on standard microbial strains: S. aureus ATCC 6538P, E. coli ATCC 8739,
      P. aeruginosa ATCC 15442 and C. albicans ATCC 10231. It was found that the drugs
      listed below inhibited growth at least one of the examined strains: Acesan 0.075
      tabl., Benuron 500 mg tabl., Chlorchex 0.5 aerosol, Methotrexat-Ebewe 500 mg
      amp., Naproxen 500 mg tabl., Nospa Forte 60 mg tabl., Platamine 50 mg amp.,
      Platidiam 50 mg amp., Sensit 50 mg drag., Septofervex 2 mg tabl., Seractil 400 mg
      tabl., Sermion 4 mg amp., Sinemet 125 mg tabl., Tarproxen 500 mg tabl. and Zyban
      150 mg tabl. It was interesting, that strong antimicrobial activity of
      methotrexate was limited to Staphylococcus aureus strain. Minimal inhibitory
      concentration of methotrexate was determined by agar dilution method with the use
      of 54 clinical S. aureus strains (MRSA-32 and MSSA-22). For MSSA strains, MIC50
      and MIC90 were 10 micrograms/ml and 20 micrograms/ml, respectively (range: 10-20
      micrograms/ml). For MRSA strains, MIC50 and MIC90 were 20 micrograms/ml and 100->
      100 micrograms/ml, respectively (range: 10-< 100 micrograms/ml).

PMID- 11293239
TI  - Monte Carlo simulation of designed helical proteins.

PMID- 11293240
TI  - Properties of protein-like heteropolymers. A Monte Carlo study.

PMID- 11293241
TI  - Differences between Desulfovibrio desulfuricans intestinal strains with respect
      to their ability of sulphasalazine biotransformation.
AB  - In presented study, differences among six intestinal Desulfovibrio desulfuricans
      strains were investigated regarding their ability of sulphasalazine (SAS)
      biotransformation. Bacterial strains were incubated (24 or 48 h) in liquid medium
      supplemented with SAS (12.2-150 microM). It has been demonstrated that
      investigated D. desulfuricans strains converted SAS with various rates, depending
      on the strain used and on time of drug contact with bacterial cells.
      Significantly different (50% coefficient of variability) were the maximum rates
      of SAS biotransformation. It was demonstrated that these rates were strongly
      dependent on the drug concentration. Increasing SAS concentrations up to about
      120 microM caused increase in the drug transformation rate. At higher SAS
      concentrations this rate remained at the same level or was inconsiderable lower.
      The strains exposed to SAS for 24 hs transformed this drug with the rate about
      twice as compared with that observed after 48 h exposition.

PMID- 11293242
TI  - The research on antioxidative properties of TOLPA Peat Preparation and its
      fractions.
AB  - The protective and therapeutic role of TPP and its fractions against lipid
      peroxidation in the mitochondria from human placenta as a model for experiments
      was evaluated. Both TPP and its fractions cause the decrease in MDA production.
      The antioxidant force of TPP and its fractions with antioxidant force of vitamin
      E was compared.

PMID- 11293243
TI  - In vivo brain microdialysis as a tool in studies of neuroprotective effects of
      cyclosporin A in acute excitotoxicity.
AB  - The mitochondrial permeability transition (MPT) resulting from calcium-induced
      opening of cyclosporin A (CsA)-sensitive megachannels, leading to deenergisation
      of mitochondria and release of pro-apoptotic cytochrome c, has been implicated in
      the pathomechanism of excitotoxic neurodegeneration. The aim of this work was to
      test neuroprotective potential of CsA in the model of N-methyl-D-aspartate-(NMDA)
      induced excitotoxicity in vivo, and to verify utility of microdialysis of the
      rabbit hippocampus in vivo for these mechanistic studies. In vitro experiments
      demonstrated that the early rapid phase of Ca(2+)-induced swelling of isolated
      brain mitochondria, and of accompanying cytochrome c release, was strongly
      inhibited by 0.5 microM CsA. In the in vivo experiments 1 mM NMDA was applied for
      20 min to the hippocampus in a control, or 5 microM CsA-containing dialysis
      medium via transhippocampal microdialysis probes, and changes in extracellular
      Ca2+ concentration and in NO release were monitored. Application of NMDA induced
      a prolonged decrease in the extracellular concentration of Ca2+, reflecting
      influx of Ca2+ to stimulated neurones. CsA only slightly enhanced this effect.
      NMDA induced also release of NO to the dialysis medium. Morphological examination
      30 min after NMDA application visualised swelling of dendritic mitochondria and
      cisternae of endoplasmatic reticulum of pyramidal neurones in the CA1 sector of
      the hippocampus in the vicinity of microdialysis probes. CsA prevented
      mitochondrial swelling. After 24 h degeneration of the CA1 pyramidal neurones
      close to a microdialysis probes was observed, which was partially prevented in
      CsA-treated rabbits. These results indicate that the mechanism of CsA
      nuroprotection may be at least in part ascribed to prevention of MPT.
      Microdialysis of the rabbit hippocampus combined with NMDA excitotoxicity
      appeared to be useful in mechanistic studies of CsA neuroprotection.

PMID- 11293244
TI  - Antimalarial activity of cyclolinopeptide A and its analogues.
AB  - Cyclolinopeptide A (CLA) is an immunosuppressive peptide of the sequence c-(-Leu
      Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe-), isolated from linseed. Since another cyclic,
      hydrophobic, immunosuppressive peptide, cyclosporin A, has potent antimalarial
      activity, CLA and a series of its analogues were synthesized on solid phase and
      tested for inhibition of the human malarial parasite Plasmodium falciparum in
      culture. The results were compared with the influence of these agents on humoral
      and cellular immune responses. There was no clear correlation between the
      structure of the peptides, their immunosuppressive activity, and their
      antimalarial activity. However, the antimalarial activity of the peptides was
      apparently connected with the strong hydrophobic nature of CLA. Substitution of a
      less hydrophobic residue into the peptide chain led to a decrease in or even loss
      of detectable activity, although such peptides retained the immunosuppressive
      properties. A possible explanation is that the antimalarial effect of CLA and
      analogues may result from their influence on cell membranes rather than on some
      specific receptor such as cyclophilin. In agreement with this idea, binding of
      CLA to purified P. falciparum cyclophilin was not detected except at very high
      concentrations. Substitution of D-aromatic residues into the CLA molecule led to
      a decrease in immunosuppressive activity but had little effect on antimalarial
      activity, which for these peptides was of the same order as for CLA. We have
      therefore demonstrated that the cyclolinopeptides are a class of compound not
      previously shown to have antimalarial activity, and that in a series of analogues
      there was no correlation between antimalarial and immunosuppressive effects.

PMID- 11293245
TI  - New tumor--inhibiting cisplatin analogues.

PMID- 11293246
TI  - The effective of methotrexate on immune response cells in rheumatoid arthritis.
AB  - Methotrexate (MTX) is one of the most used medicines in rheumatoid arthritis [r.
      a.] treatment. There are many scientific reports which present influence of MTX
      on inflammatory process. In many centers influence of MTX on cytokines level have
      been investigated. Thanks to clinical studies it has been performed that MTX
      holds up activity and productions of Il-8, releasing of TNF-alpha and reduction
      of concentration Il-6. MTX holds up proliferation of monocytes, macrophages and
      synoviocytes. It has been indicated that MTX decreases synthesis of B-4
      leucotrien in neutrophils, decreases level of neutral proteases, holds up
      cellular immunity and has antiproliferative influence on endothelial cells. There
      are reports, that MTX reduces expression of endothelial cells adhesive proteins
      and synthesis of chemotactic factors, stopping migration of leucocytes to
      tissues.

PMID- 11293247
TI  - In vitro cultures of higher plants and fungi as a potential source of bioactive
      metabolites.
AB  - The review presents the results of investigations conducted at the Chair of
      Pharmaceutical Botany, Collegium Medicum, Jagiellonian University, which
      demonstrated a prospects to obtain biologically active metabolites representative
      of many chemical groups (furanocoumarins, polysaccharides and lectins, indole
      compounds, carotenoids) in in vitro cultures of both higher plants and higher
      fungi (Macromycetes) (mycelial cultures). These cultures can be a potential,
      rich, new source of metabolites.

PMID- 11293248
TI  - The library of p-nitrophenyl esters of oligopeptides as a model to study the
      anticancer drug-peptide conjugates activated during tumor angiogenesis.
AB  - An indexed library of oligopeptide p-nitrophenyl esters immobilized via methoxy
      1,3,5-triazine scaffold on the cellulose support, was synthesized by the step by
      step procedure and by segment coupling, involving 2-chloro-4,6-dimethoxy-1,3,5
      triazine as a condensing reagent. The substrate specificity towards homogenate
      supernatant of mouse lung cancer LL2 cells has been studied.

PMID- 11293249
TI  - How should medicinal chemists read, understand and use crystallographic data?
AB  - Important experimental parameters, procedures, techniques and results of X-ray
      crystallography have been described. Also main barriers and possibilities of X
      ray methods and usefulness of an X-ray structure for medicinal chemists have been
      indicated.

PMID- 11293250
TI  - Determination of 5-aminolevulinic acid (ALA) by HPLC method.
AB  - 5-Aminolevulinic acid is at present most popular precursor of photosensitizer for
      photodynamic therapy and diagnostics. The effect of accumulation of PpIX induced
      by exogenous ALA is based on the avoidance of feedback control in the pathway of
      heme biosynthesis. For use ALA in medicine, development of analytical methods
      that will enable precise determination of content and purity is necessary. The
      ALA content is determined i. a. by titration with perchloric acid. Much greater
      problems are connected with purity determination by HPLC method. There are rather
      scarce literature data concerning purity determination of ALA by HPLC.

PMID- 11293251
TI  - Synthesis and properties of peptidomimetics--inhibitors of platelet aggregation.
AB  - The literature data on effective approaches to the development of the novel
      peptidomimetics, antagonists of fibrinogen GP IIb/IIIa receptors as potential
      antithrombotic agents are generalized and systematized in the review. The data
      obtained by the authors on the synthesis and properties of novel peptidomimetics
      are reported.

PMID- 11293252
TI  - Search for new non competitive AMPA antagonists.

PMID- 11293253
TI  - New prostaglandin analogues--prototype for drugs of immunopharmacological
      profile.

PMID- 11293254
TI  - Normal colonocytes in primary culture--an experimental model for molecular
      pharmacology and biology of large intestine.
AB  - A simple method of whole intestinal crypts isolation from rat's colonic tissue
      has been developed. Culture of viable epithelial cells (colonocytes) was obtained
      from intact crypts using method providing colonocytes for apoptosis. Satisfactory
      results have been obtained if the crypts were isolated using collagenase I. Under
      conditions applied, spontaneous release of the colonocytes took place. Liberated
      cells underwent almost immediate adhesion to microcarrier surface. The primary
      culture of normal colonocytes indicating metabolic activity for long time (> 10
      days) has been obtained.

PMID- 11293255
TI  - Ligand design package (Ludi--MSI) applied to known inhibitors of the HIV-1
      protease. Test of performance.
AB  - Performance of the Ludi (Insight II--MSI, ver. 98.0) program for computer-aided
      Ligand Design was tested using four crystallographic complexes of inhibitors with
      the HIV-1 protease. Possibility of reconstruction of the side chains and the
      peptide bond of the inhibitors, as well as attempt to construct de novo the
      central parts of these inhibitors, starting from the native structure of the
      enzyme, was studied. Results points that Ludi, although helpful, is merely
      initial tool for computer aided drug design. Moreover, some improvement of the
      program code is needed.

PMID- 11293256
TI  - Use of the quinolones in treatment of severe bacterial infections in premature
      infants.
AB  - In spite of introducing the new derivatives of fluoroquinolones into treatment in
      late 70's, the application this kind of chemotherapeutics in children is still
      controversial. The aim of our study was the evaluation of treatment efficacy and
      adverse effects associated with the application of ciprofloxacin in premature
      infants within first months of life. The investigations were performed on 36
      premature infants delivered between 25-35 gestational age with birth weight
      varied from 750-2050 grams, hospitalized in 1993-1999 in Emergency Unit and
      Department of Pediatric Propedeutics of Institute of Pediatrics of the Medical
      University of Lodz. At the beginning of the therapy the age of our patients
      varied from 10 to 202 days. Ciprofloxacin 13.8 mg/kg/day in two or three divided
      doses was administered. The time of treatment varied from 3 to 20 days. Sepsis
      was the most frequent cause of application of this drug. The following treatment
      of ciprofloxacin was performed on three children within one, two and three
      months. The efficacy was assessed as good in 66% cases of treatment course. The
      following adverse effects were observed during and after the treatment:
      thrombocytopenia (5 cases), elevated transaminases (3 cases), hyperbilirubinemia
      (3 cases), the elevation of creatinine concentration varied from 0.2 mg% to 0.6
      and from 0.1 to 0.95 mg% in two patients. Moreover one child developed femoral
      osteitis. Longitudinal studies concerning physical development and health state
      of these patients are being done.

PMID- 11293257
TI  - Aminoglycoside antibiotics--new way of dosage.

PMID- 11293258
TI  - Some computational aspects of theoretical anti-HIV drug design.
AB  - The three computational methods, the free energy perturbation (FEP), free energy
      derivative (FED) and continuum solvent molecular dynamics post analysis methods
      are presented. Application of the FEP method to improve binding properties of the
      aspartic protease JG-365 inhibitor has been demonstrated.

PMID- 11293259
TI  - The library of p-nitrophenyl esters of oligopeptides as a model to study the
      anticancer drug-peptide conjugates activated during tumor angiogenesis.
AB  - An indexed library of oligopeptide p-nitrophenyl esters immobilized via methoxy
      1,3,5-triazine scaffold on the cellulose support, was synthesized by the step by
      step procedure and by segment coupling, involving 2-chloro-4,6-dimethoxy-1,3,5
      triazine as a condensing reagent. The substrate specificity towards homogenate
      supernatant of mouse lung cancer LL2 cells has been studied.

PMID- 11293260
TI  - Theoretical models of interactions between buspirone analogues and 5-HT1A and 5
      HT2A serotonin receptor subtypes.
AB  - In present study the structure-selectivity relationship of buspirone and six of
      its analogues towards 5-HT1A and 5-HT2A serotonin receptors was investigated on
      molecular level. Molecular mechanics energy minimisation and advanced molecular
      dynamics (MD) simulations allowed us to perform a dynamic structural analysis of
      transmembrane helical domains of the human 5-HT1A and 5-HT2A receptors and
      investigate the ligand-induced changes of the entire structure of the ligand
      receptor complex. The obtained results suggest, that helical and extracellular
      domains of both receptors have different topography of the putative binding sites
      and also different dynamical behaviour. The results of this study are consistent
      with experimental site-directed mutagenesis data and binding affinities of
      examined ligands towards both serotonin receptors.

PMID- 11293261
TI  - Investigation of lavandulifolioside by mass spectrometry.
AB  - The different kind of ionisation techniques in mass spectrometry were applied to
      obtain mass spectra giving structural information and confirmation of molecular
      weight of the investigated natural product: lavandulifolioside [3,4-dihydroxy
      beta-phenylethoxy-O-beta-D-arabinopyranosyl-(1-->2)-alpha- L-rhamnopyranosyl-(1-
      >3)-4-O-beta-caffeoyl-beta-D-glucopyranoside]. Atmospheric Pressure Chemical
      Ionisation APCI MS with positive polarisation gave the best results. In the APCI
      mass spectra in negative mode pseudomolecular ion [M-H]- was observed at m/z =
      755. The fragmentation of the investigated compound undergoes in two routes: 1.-
      subtraction of arabinose, followed by loss of caffeoyl moiety (HO)2C6H3CH=CHCO
      and rhamnose and the last two in the opposite way; 2.--subtraction of caffeoyl
      moiety, next arabinose, subsequent rhamnose. The structure of molecule with the
      glucose built between caffeic acid (3,4-dihydroxycinnamic acid) and 3,4
      dihydroxyphenylethanol, and sugar sequence (rhamnose connected to glucose
      followed by arabinose), were confirmed.

PMID- 11293262
TI  - Synthesis of new N-substituted cyclic imides with an expected anxiolytic
      activity. XV. Derivatives of 2-ethyl-1.4-dimethoxy-dibenzo[e.h]bicyclo[2.2.2]
      octane-2.3-dicarboximide.
AB  - The preparation of a number of derivatives of dibenzo[e.h]bicyclo[2.2.2]octane
      2.3-dicarboximide with an expected anxiolytic activity.

PMID- 11293263
TI  - The antitumor effect of postoperative treatment with genistein alone or combined
      with cyclophosphamide in mice bearing transplantable tumors.
AB  - Genistein has been shown to be an inhibitor of tumor growth as well in vitro as
      in vivo. In addition to its antitumor effect, genistein reveals the
      antimetastatic and antiangiogenic properties. In this paper we described the
      results of our studies on the antimetastatic activity of genistein alone or
      combined with cyclophosphamide (CY) in mice which before this treatment were
      exposed to surgical excision of the primary tumor. Three transplantable
      subcutaneously growing mouse tumors were applied: Lewis lung cancer (LL2), B16F
      10 melanoma and 16/C mammary cancer. The antitumor and antimetastatic effect was
      evaluated by the estimation of a number of lung colonies and a number of primary
      tumor recurrence as compared to the control mice exposed to the s.c. tumor
      extirpation only. Twenty days after the surgery, an average of 52 lung tumor
      colonies per mouse were detected in control mice bearing LL2 cancer. The
      treatment with genistein resulted in the reduction of the lung colonies to 24 per
      mouse. The treatment with CY reduced the number of lung colonies to 12 (p < 0.05)
      and combined treatment with both agents to 4 (p < 0.05). The percentage of
      primary tumor recurrence was 25, 86, 67 and 80% in the control, genistein
      treated, CY treated, and genistein + CY treated mice, respectively. Twenty days
      after the surgery, no lung metastases in the control mice bearing B16F-10
      melanoma were observed. The percentage of primary tumor recurrence in the
      control, genistein treated, CY treated and genistein + CY treated mice was: 86,
      29, 57 and 67% respectively. Two different protocols of the treatment with
      genistein were applied in 16/C mammary cancer model. In the first one genistein
      was injected before and in the other after surgical excision of tumor. The
      histological examination revealed the presence of lung metastases in all,
      untreated and treated, according to both protocols groups of mice. The percentage
      of primary tumor recurrence in the control mice, genistein treated according to
      the protocol I, and II was: 100, 40, and 40%, respectively.

PMID- 11293264
TI  - Synthesis of new N-substituted cyclic imides with an expected anxiolytic
      activity. XIV. Derivatives of 1.4-diethoxy-dibenzo[e.h]bicyclo[2.2.2]octane-2.3
      dicarboximide.
AB  - The preparation of a number of derivatives of dibenzo[e.h]bicyclo[2.2.2]octane
      2.3-dicarboximide with an expected anxiolytic activity.

PMID- 11293265
TI  - Synthesis of new N-substituted cyclic imides with an expected anxiolytic
      activity. XIII. Derivatives of 1-methoxybicyclo[2.2.2]oct-5-ene-2,3
      dicarboximide.
AB  - The preparation of a number of derivatives of 1-methoxybicyclo[2.2.2]-oct-5-ene
      2,3-dicarboximide possessing an expected anxiolytic activity has been described.

PMID- 11293266
TI  - Synthesis of new N-substituted cyclic imides with an expected anxiolytic
      activity. XI. Derivatives of 7-diphenylmethylenebicyclo[2.2.1]hept-2-ene-5,6
      dicarboximide.
AB  - The preparation of a number of new N-substituted derivatives of 7
      diphenylmethylenebicyclo[2.2.1]hept-2-ene-5,6-dicarboximide with an expected
      anxiolytic activity.

PMID- 11293267
TI  - Synthesis of new N-substituted cyclic imides with an expected anxiolytic
      activity. XII. Derivatives of N-hydroxy-1,4-dimethyl-dibenzo[e.h]bicyclo[2.2.2]
      octane-2,3-dicarboximide.
AB  - The preparation of a number of derivatives of N-hydroxy-1,4-dimethyl
      dibenzo[e.h]bicyclo[2.2.2]octane-2,3dicarboximide with a potential activity on
      central nervous system has been described.

PMID- 11293268
TI  - Kinetics of thermal decomposition of buspirone hydrochloride in solid state.
AB  - Stability of buspirone hydrochloride (BH) in solid state has been studied. The
      content of BH and changes in its concentration during preliminary kinetic studies
      of the stability of this drug in BUSPAR tablets and in substance were assessed by
      spectrophotometry in UV, after previous chromatographic separation lambda max =
      239 nm (A1%1 cm = 502 in 50% aqueous methanol solution). Using thin layer
      chromatography several breakdown of buspirone were detected.

PMID- 11293269
TI  - High-performance liquid chromatographic analysis for the determination of
      buspirone analogue--mesmar in rat plasma.
AB  - A simple and selective analytical method for the determination of buspirone
      analogue--mesmar in rat plasma is described. The procedure involves liquid-liquid
      extraction followed by reversed-phase high-performance chromatographic analysis
      with UV detection at 245 nm. No endogenous compounds were found to interfere. The
      absolute extraction recovery from plasma samples was 76%. The linearity was
      assessed in the range 0.12-2.44 nmol/ml. Stability of mesmar during processing
      (autosampler) and in plasma was checked. This method proved suitable for
      pharmacokinetic studies following single oral dose in rats.

PMID- 11293270
TI  - Pyrrole analogues of chloramphenicol. II. Synthesis and antibacterial activity of
      DL-threo-1-(1-methyl-5-nitro-pyrrole-2-yl)-2-dichloroacetamidopropane-1, 3-diol.
AB  - The seven-stage synthesis of a pyrrole analogue of chloramphenicol (VII) was
      described. The compound exhibits a significant antibacterial activity.

PMID- 11293271
TI  - Synthetic analogues of netropsin and distamycin. VI. Synthesis of carbocyclic
      lexitropsins containing a bioreductive element.
AB  - Carbocyclic derivatives of lexitropsines containing of two aromatic rings, N
      dimethylaminopropyl group lonked to carboxyl terminus and 5-[bis(2-chloroethyl)
      amino]-2,4-dinitrobenzamide group linked to the amino terminus group were
      synthesed. The N-terminal group should present selective alkylating activity on
      the DNA of cancer cells in conditions of hypoxia.

PMID- 11293272
TI  - Self-organizing neural networks for modeling 3D QSAR--a comparative study.
AB  - Different architectures of self-organizing neural networks (SOM) have been used
      for modeling 3D QSAR. The atomic coordinates and partial atomic charges were used
      as input signals. In particular, the steroids complexing corticosteroid binding
      globulin (CBG) that are used as a benchmark measuring the performance of drug
      design methods have been applied to compare between individual methods. The
      sensitivity of the different architectures for changes of the alignments of the
      molecules within series, as well as the possibility for alignments based on the
      molecular inertial axes have been tested.

PMID- 11293273
TI  - Screening and search for novel inhibitors of DD-peptidase 64-575.
AB  - The aim of the work was search for inhibitors of PBPs (penicillin binding
      proteins, DD-carboxypeptidase/transpeptidase, DD-peptidase). Between 141 tested
      Streptomyces strains, 25% showed activity of inhibitors production. The
      inhibitors were produced by selected Streptomyces strains (NIH Culture
      Collection). The culture supernatants of Streptomyces rimosus B PZH (inhibitor B)
      and Streptomyces rimosus NRRL 2234 (inhibitor 2234) exhibited the highest
      inhibition activity. Both inhibitors were purified by the use of: anion exchange
      chromatography and reversed phase chromatography (HPLC). Inhibitor B is a gamma
      lactam compound and inhibitor 2234 is a beta-lactam.

PMID- 11293274
TI  - A search for new glucophores by isosteric replacement of carboxylic function.
AB  - We used arylsulfonylalkanoic acids as parent structures for designing new
      potential sweeteners. The Kohonen maps of the molecular electrostatic potential
      of the possible bioisosteric replacements of carboxylic function have been
      simulated and used for the selection of the potential synthetic targets which are
      now under synthesis.

PMID- 11293275
TI  - Correlation of fungostatic activity with log P and sigma parameters in the group
      of thiobenzanilides.
AB  - 2,4-Dihydroxythiobenzanilide and its analogues were recently found to show strong
      biological activity. Earlier works exhibited that their biological activity
      depends strongly on their lipophilicity determined by means of RP-HPLC. Among
      others, fungostatic activity against tested yeast and mould strains appeared to
      be comparatively poorer modelled by chromatographic lipophilicity parameters.
      Very high correlation (r approximately 0.85-0.9) with these activities was
      obtained by means of multiparameter regression analysis where calculated log P
      and Hammet sigma values were involved as the independent variables. Analysed data
      show that activity against yeast and mould fungi is a superposition of two basic
      properties of thiobenzanilides: their lipophilicity and electronic properties.

PMID- 11293276
TI  - Patent protection of pharmaceuticals.
AB  - Patenting of biologically active compounds by academic institutions is discussed,
      with emphasis on patents for already known compounds.

PMID- 11293277
TI  - Synthesis and biological evaluation of selected insect neuropeptide analogs
      modified by D- or L-phenylglycine derivatives.
AB  - Novel analogs, modified by L- or D- phenylglycine and p-substituted derivatives,
      of the neuromodulator proctolin (Arg-Tyr-Leu-Pro-Thr) and of the Trypsin
      Modulating Oostatic Factor from the gray flesh fly Neobellieria bullata (Neb-TMOF
      Asn-Pro-Thr-Asn-Leu-His) were synthesized and checked for activity. Proctolin
      analogs were modified at position 2: Arg-Phg-Leu-Pro-Thr (I), Arg-D-Phg-Leu-Pro
      Thr (II), Arg-Phg(p-OH)-Leu-Pro-Thr (III), Arg-D-Phg(p-OH)-Leu-Pro-Thr (IV), Arg
      Phg(p-NO2)-Leu-Pro-Thr (V) Arg-D-Phg(p-NO2)-Leu-Pro-Thr (VI), Arg-Phg(p-NH2)-Leu
      Pro-Thr (VII), Arg-D-Phg(p-NH2)-Leu-Pro-Thr (VIII), Arg-Phg(p-N,N-di-Me)-Leu-Pro
      Thr (IX), Arg-D-Phg(pp-N,N-di-Me)-Leu-Pro-Thr (X) while analogs of Neb-TMOF
      underwent modifications at position 6: Asn-Pro-Thr-Asn-Leu-Phg(p-NO2) (XI), Asn
      Pro-Thr-Asn-Leu-D-Phg(p-NO2) (XII), Asn-Pro-Thr-Asn-Leu-Phg(p-NH2) (XIII), Asn
      Pro-Thr-Asn-Leu-D-Phg(p-NH2) (XIV), Asn-Pro-Thr-Asn-Leu-Phg(p-N,N-di-Me) (XV),
      Asn-Pro-Thr-Asn-Leu-D-Phg(p-N,N-di-Me) (XVI). Earlier studies on proctolin
      demonstrated that the presence of the -CH2- group between C-alpha and the phenyl
      ring at position 2 of the peptide chain is important for the myotropic activity.
      Based on these results, we replaced Tyr at position 2 by different phenylglycine
      derivatives, lacking the methylene group at the side chain. Myotropic activity of
      the proctolin analogs was assayed in vitro on the semi-isolated heart of the
      mealworm Tenebrio molitor and on the foregut of the locust Schistocerca gregaria.
      All analogs (I-X) were practically inactive. For Neb-TMOF, it was previously
      demonstrated that the exchange of His-6 by p-substituted Phe-derivatives,
      especially by Phe(p-NH2), an amino acid containing a basic function, results into
      analogs which inhibit trypsin biosynthesis in the gray fleshfly. For this reason
      these new Neb-TMOF analogs with L- or D-phenylglycine p-substituted derivatives
      at position 6, were developed and tested (in vivo) in the trypsin biosynthesis
      assay of the gray fleshfly N. bullata. Only analogs XV and XVI slightly inhibited
      trypsin biosynthesis in the midgut. Because more than 50% of the injected animals
      died and none of the surviving animals ate much of the liver meal, the lower
      trypsin level in the gut might be a indirect effect. Other peptides (XI-XIV) had
      no effect on the level of trypsin biosynthesis in the midgut.

PMID- 11293278
TI  - Animal model of ethanol abuse: rats selectively bred for high and low voluntary
      alcohol intake.
AB  - The selectively bred alcohol-preferring and alcohol-non-preferring lines of rats
      have been used to study the biology of alcohol abuse and dependence. In our
      laboratory new lines of Wistar rats have been selectively outbread for 7 years
      and 19 generations for high and low ethanol intake (WHP--Warsaw High Preferring)
      and WLP--Warsaw Low Preferring respectively). After the first selection
      procedure, the highest scoring females and males were used initiate upward
      selection, while the lowest scoring pairs were used to initiate downward
      selection. Mated pairs were housed in breeding cages, pups were allowed to nurse
      for 3 weeks before weaning, then the pups of each litter were culled to the same
      sex cage and allowed to mature until they were subjected to the selection
      procedure. In order to determine the alcohol intake and preference, the rats were
      individually housed in wire cages containing two graduated drinking tubes mounted
      at the front. During the entire investigation, the subjects had free access to
      standard lab chow (Bacutil, Poland). Ethanol solution was prepared from 95% stock
      ethanol and tap water. The animals were presented with 10% ethanol solution and
      water (two-bottle choice test). The drinking tubes were rotated daily to prevent
      position preference. Alcohol intake was calculated as average g/kg/day (absolute
      ethanol) while alcohol preference (in %) was calculated as the amount of alcohol
      consumed/total fluid x 100. Our results (17-19 generations) have shown that mean
      alcohol intake in WHP rats was higher than 5.0 g/kg/24 h ethanol, while WLP rats
      generally consumed less than 2.0 g/kg/24 h ethanol. Our results also showed that
      the total fluid intake in WHP rats slightly but not significantly higher as
      compared with WLP rats. Maximal ethanol consumption (in both lines) occurred
      during the natural dark phase three bungs (19.00-20.00 hrs, 23.00-02.00 hrs and
      04.00-05.00 hrs). Interestingly, the intakes of high concentrations of sucrose
      and saccharin solutions were significantly higher in WHP than in WLP rats.
      Furthermore, the WHP rats reduced their alcohol and water intakes in the presence
      of 10% sucrose solution. Thus, it appears that high consumption of sweets may be
      a neurobiological factor promoting increased ethanol intake by WHP rats.

PMID- 11293279
TI  - Favourable interactions of cytostatic and steroid drugs in treatment of systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (referred to below as SLE) is a disorder associated
      with formation of immune complexes in the circulatory system and their deposition
      in the internal organs, as well as in the skin. The disease can appear at any
      age, but the vast majority of cases are women between 15 and 40 years of age. The
      paper presents the case of a thirty-year-old woman with systemic lupus
      erythematosus. She was admitted to hospital because of erythematous and
      haemorrhagic lesions in the skin of her face, hands and feet and febrile states.
      SLE was diagnosed in the patient on the basis of criteria established by the
      American Rheumatological Association. The following abnormalities were observed
      in the patient: skin lesions of erythematous type on the face, hypersensitivity
      to UV light, erosions of the mucous membranes of the oral cavity, changes in the
      kidneys confirmed by biopsy, haematological symptoms, immune disorders.
      Additional criteria to establish the diagnosis included: febrile states.
      Raynaud's sign, hair loss, presence of immunoglobulin complexes in the skin,
      decreased complement level. The paper discusses modern therapy of visceral lupus
      erythematosus, based on corticosteroids and immunosuppressants. The interactions
      of these drugs were observed in the patient. The woman was treated with combined
      corticosteroid and cytostatic therapy, which led to the remission of the
      pathologic process confirmed by the clinical condition of the patient and
      laboratory tests.

PMID- 11293280
TI  - The effect of gamma-radiation on nitroimidazole derivatives.
AB  - The effect of gamma irradiation, in doses from 10 to 50 kGy on physical and
      chemical properties of metronidazole, ornidazole and tynidazole in solid state
      has been studied. Results of the measurements by the UV, IR, TLC, EPR, DSC
      methods revealed the presence of free radicals, products of decomposition, an
      increase in the melting point and a decrease or increase in the content of the
      substance studied. Microbiological assays proved that sterilization of the
      compounds studied was effective even with the smallest irradiation dose applied.
      The maximum tolerated dose and the safe sterilisation dose were determined.

PMID- 11293281
TI  - Irritation of gastrointestinal mucosa by new glycosyl derivative of diclofenac in
      comparison with diclofenac in rats.
AB  - We have obtained new glycosyl derivative of diclofenac 3 and studied its
      ulcerogenic effect in the gastrointestinal system. Diclofenac as free acid 1 and
      its derivative 3 were administered to rats per os in a single dose 20 mg/kg and
      in 5 doses of 5 mg/kg. Single dose of derivative 3 caused less irritation than 1;
      after multiple administration no irritating effect of derivative 3 was seen.

PMID- 11293282
TI  - Aspects of childhood cancer during the Byzantine period.
AB  - The main trends in the diagnosis and management of childhood cancer during the
      Byzantine period (330-1453 CE) are investigated. Therapeutic modalities reflected
      the influences from Ancient Greek and Greco-Roman medicine. Medical treatment
      included a great variety of regimens, and surgery was not unknown. The attitudes
      toward cancer suggest that people of that time did not believe in a superstitious
      origin of the disease. Even though most of these remedies and many procedures are
      nowadays out of use, the physicians of the Byzantine period preserved the
      scientific medical thought of antiquity, improved it, and set the basis of
      current achievements. Medical terms introduced during the Byzantine period are
      still used. The texts have been studied in their original languages, that is,
      Ancient and Byzantine Greek, and Latin.

PMID- 11293283
TI  - Immunoglobulin class and subclass concentrations after treatment of childhood
      leukemia.
AB  - With greatly increased survival rates after childhood leukemia during the last 3
      decades, the long-term effects of the treatment have become more evident. The
      disease and its treatment impair the immune system, but the duration of this
      impairment is unknown. The authors studied the serum concentrations of
      immunoglobulins and IgG subclasses in 20 Icelandic children cured of leukemia on
      average 8 years and 3 months after their treatment ended. Although no marked
      deviations were found in the concentrations of the main immunoglobulin classes
      IgA, IgM, IgG, and IgE, the IgG subclass levels were below reference values. The
      patients had on average 0.9 of age standardized reference values of IgG1, 0.5 of
      IgG2, 0.8 of IgG3, and 0.7 of IgG4. However, none had any autoimmune diseases or
      a markedly increased tendency for infections. The results indicate that although
      the immunoglobulin classes regain their normal values within a few years after
      cessation of treatment, recovery of the IgG subclasses, especially IgG2, is
      impaired.

PMID- 11293284
TI  - Long-term follow-up of children with retinoblastoma.
AB  - Twenty-one pediatric retinoblastoma (RB) patients treated between 1976 and 1994
      were evaluated for late treatment-related complications. Median age at diagnosis
      was 24 months; median age at follow-up was 12 years; median follow-up time was 12
      years. Of the 21 patients, 14 had unilateral RB and 7 had bilateral RB. Thirteen
      patients had received external radiotherapy and 8 children were treated by
      chemotherapy. Twenty-one patients had undergone enucleation. Radiation-induced
      cataracts were found in 3 patients, radiation retinopathy in 1, enucleation and
      postradiotherapy contracted socket in 1, very low visual acuity postradiotherapy
      in 3, severe hypotelorism in 2, growth hormone deficiency in 2, neurocognitive
      disorders in 6, and orbital deformation due to radiation bone atrophy was
      moderate-severe in 12 patients. Azoospermia was found in 1 patient treated by
      cyclophosphamide and vincristine. The most frequent sequela in this group of RB
      cured children were postradiotherapy orbital deformation due to bone atrophy and
      neurocognitive disabilities. Late radiation effects must be avoided by using
      modern, innovative, and more sophisticated radiotherapeutic techniques. Late
      treatment-related complications justify the long-term follow-up of childhood RB
      survivors.

PMID- 11293285
TI  - The risk of dental caries in childhood cancer is not high if the teeth are caries
      free at diagnosis.
AB  - The aim of this work was to evaluate whether the cancer itself, age, sex, number
      of days of fever, and septic and fungal episodes affect the salivary samples and
      to assess the frequency of the development of caries during cancer. The
      background features for caries challenge were studied by monitoring changes in
      counts of salivary lactobacilli and candida for up to 1 year in 36 children
      during anti-cancer therapy (18 leukemias and 18 solid tumors). The first dental
      examination was performed at the diagnosis of cancer and a reexamination about 3
      years later. The results showed that the children with active caries at the
      diagnosis of cancer had significantly more positive findings of lactobacilli and
      candida than did those with a sound dentition. The other background features did
      not affect the results. The follow-up dental examination showed that 86.7% of the
      children who had a caries-free dentition at the beginning of the survey were
      still in this state after 3 years. In conclusion, more attention should be paid
      to prophylaxis and dental treatment for cancer children with caries.

PMID- 11293286
TI  - Prognostic value of day 14 blast percentage and the absolute blast index in bone
      marrow of children with acute lymphoblastic leukemia.
AB  - The product of the percentage blasts on the bone marrow aspirate (BMA) and the
      biopsy cellularity has been termed the "absolute blast index aspirate" (ABI
      aspirate) and is used to measure disease response on day 7 of induction therapy.
      The authors compared the event-free survival (EFS) in high-risk and standard-risk
      patients as identified by the ABI-aspirate and the BMA percentage blasts on day
      14 of induction therapy. Both indices identified high-risk cases. EFS of patients
      categorized as high-risk by these 2 methods and the high-risk criteria used by
      the authors' service (WCC of > 20 x 10(9)/L, age < 2 and > 8 years and a
      peripheral blood blast count of > 1.0 x 10(9)/L on day 8 of induction) did not
      differ. There was concordance between patients identified as high risk by all 3
      methods. The results confirmed the prognostic value of the ABI-aspirate and the
      BMA percentage blasts on day 14 of induction therapy, but these methods were not
      superior to the high-risk criteria currently in use.

PMID- 11293287
TI  - Successful immunization following cord blood transplantation in a child with
      Diamond-Blackfan anemia.
AB  - Cord blood transplantation (CBT) has been increasingly used to treat patients
      with hematological diseases, but active immunizations for patients have not been
      described. Patients certainly need immunizations following CBT, since
      transplanted cord blood is naive. The authors previously reported successful
      hematopoietic reconstitution following cord blood transplantation from an HLA
      matched sibling in a transfusion-dependent child with Diamond-Blackfan anemia. No
      graft-versus-host disease, either acute or chronic, has been observed so far.
      Here, the authors report that immunological recovery of the patient has been
      rapid shortly after CBT and immunization has been done successfully. Vaccines
      (diphtheria, pertussis, tetanus, rubella, measles, and BCG) were administered
      during 22-34 months post-transplant. Seroconversion to these vaccines was
      excellent without significant adverse effects. These results indicate that both
      toxoid and live vaccines have been safely administered in the patient who
      underwent related cord blood transplantation.

PMID- 11293288
TI  - Langerhans cell histiocytosis: central nervous system involvement treated
      successfully with 2-chlorodeoxyadenosine.
AB  - A case of disseminated Langerhans cell histiocytosis with resistant central
      nervous system (CNS) disease in an adolescent is described. The child presented
      with visible cranial lesions, emesis, headaches, and short-term memory loss.
      Diagnostic evaluation revealed multiple osseous lesions in the cranium, ribs,
      vertebral bodies, and pelvis. The clinical course with complications and response
      to each therapy are sequentially reviewed. Remission, as evidenced clinically and
      by magnetic resonance imaging, was ultimately accomplished with 2
      chlorodeoxyadenosine (2-CDA). The full course of 2-CDA was not tolerated due to
      bone marrow suppression. CNS histiocytosis is known to be resistant to therapy.
      Earlier introduction of 2-CDA for CNS disease might offer more successful
      treatment with less toxicity than seen in patient.

PMID- 11293289
TI  - Transplanted peripheral blood stem cells, mobilized by chemotherapy alone, can
      induce persistent hematopoiesis in children with acute leukemia.
AB  - Three patients with leukemia were transplanted with peripheral blood stem cells
      mobilized by intensification or maintenance chemotherapy alone. They maintained
      persistent reconstituted hematopoiesis for at least 9 years. The experience
      provides evidence that long-term marrow repopulating cells can be mobilized into
      the blood to an adequate repopulating extent by chemotherapy alone.

PMID- 11293290
TI  - Euthyroid sick syndrome in children with Hodgkin disease.
AB  - Euthyroid sick syndrome is related to profound changes in thyroid metabolism
      induced by nonthyroidal diseases. To determine whether children with newly
      diagnosed Hodgkin disease might present thyroid abnormalities and to establish
      their predictive value, the authors performed regular thyroid function testing.
      Seven children (5 M, 2 F) with a mean age of 10.4 years (range: 4.6-15 years) at
      diagnosis were studied for a period of 6.9 years (4.2-10.5 years). Five patients
      presented at diagnosis with euthyroid sick syndrome characterized by borderline
      low thyroxine circulating levels (T3 0.8-1.3 ng/mL, FT3 1.5-1.7 pg/mL) and mildly
      raised TSH (4.6-5 microU/mL). Thyroid function turned normal within 6 months of
      therapy. Subsequently, 3 children developed overt hypothyroidism (T4 35-40 ng/mL,
      FT4 2-7 pg/mL, TSH 5.5-11 microU/mL) requiring substitution therapy. Euthyroid
      sick syndrome was not associated with a poorer outcome in terms of survival or
      long-term thyroid consequences. Thyroid function testing should be performed
      routinely at diagnosis and thereafter in children with Hodgkin disease to detect
      subtle abnormalities.

PMID- 11293291
TI  - Parotid mucoepidermoid carcinoma following chemotherapy for childhood acute
      lymphoblastic leukemia.
AB  - Primary parotid gland tumors are rare during childhood; however, these tumors are
      more common as second malignant neoplasms following radiation therapy. The
      authors report a case of secondary parotid mucoepidermoid carcinoma after
      chemotherapy for childhood acute lymphoblastic leukemia.

PMID- 11293292
TI  - Spontaneous rupture of mediastinal cystic teratoma into the pleural cavity:
      report of two cases and review of the literature.
AB  - The authors report on two female patients aged 12 and 14 years, who spontaneously
      developed a rupture of benign mediastinal cystic teratoma into the right pleural
      cavity. They presented with acute onset of severe chest pain and respiratory
      distress. The tumors were completely resected by thoracotomy. The serum and
      pleural fluid levels of carcinoembryonic antigens, CA-125 and CA19-9 were
      invariably elevated, then decreased to normal range after the surgical resection.
      Rapid diagnosis of this extremely rare complication is important because it may
      progress to a life-threatening condition.

PMID- 11293293
TI  - Klebsiella pneumoniae meningitis in thalassemia major patients.
AB  - Two thalassemia major patients received regular blood transfusion and
      desferrioxamine chelation, and 1 patient had a splenectomy at 9 years of age.
      Both patients developed Klebsiella pneumoniae meningitis at age of 27 and 15
      years. They died within a short time despite appropriate antibiotic treatment.
      Klebsiella meningitis may be more common in transfusion-dependent thalassemia
      patients.

PMID- 11293294
TI  - [Prevention of the health effects of air pollution: intersectorial political
      strategies for adopting the National Health Plan].
AB  - Thirty to 40% of European citizens are exposed to air pollution levels above EU
      standards. Recent epidemiological studies, both in Italy and elsewhere, have
      shown that excess mortality and morbidity may occur in relation to air pollutant
      concentrations below current standards. EU is trying to work out a strategy of
      interventions for the reduction of air pollution. Italian policies in the field
      of air quality have been fragmentary. However, the Italian National Health Plan
      (NHP) 1998-2000 aims at: 1) contrasting the current division between health and
      environmental policies; 2) giving priority to a renewed focus on prevention; 3)
      improving a strict cooperation to solve the problem. A specific aim of the NHP
      consists in the reduction of private vehicular traffic. In conclusion, an
      integrated strategy of international, national and local policies is needed,
      based on a wide information exchange among risk evaluators and decision-makers.
      Likewise, strong efforts in communicating scientific evidences and public health
      policies to the large public are needed, in order to elicit an active
      participation to environmental control interventions.

PMID- 11293295
TI  - [Polluting agents and sources of urban air pollution].
AB  - This paper is an up-to-date review of the scientific evidence on mechanisms of
      pollutant generation and health effects for a number of urban air pollutants. The
      review focuses on main sources and health effect of ozone and photochemical smog,
      benzene, polycyclic aromatic hydrocarbons, and particulate matter. These agents
      are "priority pollutants", generated by vehicle traffic, and their regulation is
      currently being examined by the European Council and the European Commission. The
      aim is to reach, by the year 2010, values lower than 180 micrograms/m3 for ozone
      as maximum hourly concentration, 2.5 micrograms/m3 for benzene as an annual
      average, 93 micrograms/m3 for nitrogen dioxide as 98 degrees percentile of hourly
      concentrations, 50 micrograms/m3 for particulate as a daily average. The goal can
      be achieved only by means of immediate interventions on emissions.

PMID- 11293296
TI  - [Database of air pollution and air quality indicators for the principal Italian
      cities: the ITARIA-WHO project].
AB  - This paper presents air quality data collected in eight Italian cities (Turin,
      Genoa, Milan, Bologna, Florence, Rome, Naples, Palermo) during the period 1994
      98. Storage and analysis of data have been performed by the ITARIA collaborative
      group in the framework of a national study promoted by ECEH-WHO, aimed at
      evaluating the health impact of urban air pollution. Methods used to compare data
      from different networks are described. A slight reduction in the annual mean
      concentrations of NO2, SO2 and CO over the period under study was observed.
      However, for most of the cities, national and European air quality standards are
      frequently exceeded also in 1998, particularly for ozone pollution.

PMID- 11293297
TI  - [Concentrations of PM10 and PM2.5 particulate material in the atmosphere of
      Rome].
AB  - Starting from 1993, various monitoring campaigns were carried out in Rome to
      determine PM10 and PM2.5. Their results are presented here cumulatively, with the
      aim of obtaining preliminary information on relationships among these size
      fractions, in various seasonal periods and in two sites with different
      characteristics (a road site and an urban background site in a public park).
      Particles were collected on filter and gravimetrically determined. Both PM10 and
      PM2.5 concentrations show temporal fluctuations with higher values during winter
      months. Background concentrations are lower than those contemporaneously measured
      at the road site only to a limited extent (10-17%). The contribution of PM2.5 to
      PM10 during the winter semester is higher than during the summer one (67 vs.
      52%), with no substantial intersite differences.

PMID- 11293298
TI  - [Benzene exposure among urban traffic wardens in the City of Rome: preliminary
      results of a pilot project].
AB  - In the framework of a research project on short-term effects of human exposure to
      atmospheric pollutants, a survey on personal exposure to benzene and related
      aromatic hydrocarbons in traffic wardens has been carried out. Approximately two
      hundred subjects, namely 143 policemen involved in traffic control and 63 office
      clerks, have been enrolled in the study. Spot measurement of personal exposure to
      volatile aromatic hydrocarbons have been performed along the period December 1998
      June 1999 using passive dosimeters. In addition, blood benzene and urinary trans
      muconic acid and phenyl mercapturic acid have been determined at the beginning
      and at the end of workshift. The results so far obtained suggest average levels
      of exposure to benzene around 10 micrograms/m3 (7 h time weighted average) for
      traffic wardens, and about three fold lower levels for indoor workers. Average
      values of benzene exposure recorded for policemen are basically comparable to
      background levels measured in the urban area. Nevertheless, some outlier values
      indicate that distinct higher exposure values may be occasionally experienced by
      traffic wardens. Internal exposure biomarkers were not significantly different
      between policemen and office workers. Yet, both urinary trans-muconic and phenyl
      mercapturic acids were significantly increased in smokers compared to non
      smokers, irrespective of their job.

PMID- 11293299
TI  - [Acute effects of air pollution in Rome].
AB  - Two time-series studies, aimed at evaluating the acute health effect of air
      pollution among Rome inhabitants, were carried out. In the first study the
      correlation between daily mortality (1992 to 1995) and daily concentrations of
      five air pollutants (particles, SO2, NO2, CO, O3) was analyzed. In the second
      study the association between daily levels of the same pollutants and hospital
      admissions for respiratory and cardiovascular disease (1995-97) was evaluated.
      Poisson regression models were used to estimate the association between pollutant
      levels and health effect variables; the models included smooth functions of day
      of study, mean temperature, mean humidity and indicator variables for day of the
      week and holidays. Daily total mortality was associated with particle average
      concentration on that day and with NO2 levels of one or two days before. Hospital
      admissions for cardiovascular disease were positively correlated to particles,
      SO2, NO2, e CO. Hospital admissions for respiratory disease were associated with
      NO2 and CO levels of the same day and of two days before among children (0-14
      years) and among adults (15-64 years). Increments of ozone were associated with
      increments of total respiratory and of acute respiratory diseases in children (0
      14 years).

PMID- 11293300
TI  - [Features of traffic near houses and respiratory damage in children: the results
      of the SIDRIA (Italian Study on Respiratory Problems in Childhood and the
      Environment)].
AB  - A survey was conducted between 1994 and 1995 in ten areas of northern and central
      Italy in a representative sample of 39,275 children in two age groups (6-7 and 13
      14 years; response rate: 94.4%). Detailed information on respiratory health and
      on exposure to several risk factors, including traffic patterns near their
      residence, was collected through standardized questionnaires, filled in by
      parents (and also by subjects of 13-14 years). For children living in
      metropolitan areas, a clear association was found between a high flow of heavy
      vehicles near their residence and several respiratory conditions. Combining the
      current symptoms in mutually exclusive groups, a stronger association was
      detected for children reporting only bronchitic symptoms, with an odds ratio (OR)
      of 1.44 (95% confidence interval: 1.17-1.78), whereas the OR for those reporting
      only asthma or wheeze was 1.10 (0.96-1.26). Weaker associations were found in
      relation to more generic traffic indicators and for children living in non
      metropolitan areas.

PMID- 11293301
TI  - [Air pollution from traffic and the risk of tumors].
AB  - This paper describes the epidemiological evidence on lung cancer and childhood
      leukemia in relation to traffic-related air pollution, with particular reference
      to diesel exhausts, polycyclic aromatic hydrocarbons (PAH) and benzene. Recent
      epidemiological studies strengthen the hypothesis of an increased lung cancer
      risk related to residential exposure to air pollution and to occupational
      exposure to diesel exhausts. The evidence on the carcinogenicity of several PAH
      mixtures comes from occupational studies, while the risk incurred by the general
      population is difficult to estimate. A few papers suggest that traffic-related
      air pollution may be associated with an increased risk of childhood leukemia. The
      observed relative risks are small but the exposure is widespread. Therefore, the
      overall impact of exposure to current levels of urban air pollution may be
      substantial.

PMID- 11293302
TI  - Effects of cell banking manipulations on ex vivo amplification of umbilical cord
      blood.
AB  - The small volume of placental/umbilical cord blood (PUCB) collectable restricts
      the use of these stem cells to pediatric transplantation. To extend the use of
      PUCB to adult recipients, many laboratories are investigating the feasibility of
      ex vivo PUCB expansion. The present study analyses the effects that PUCB banking
      cell manipulations (cell sedimentation, cryopreservation and thawing, mononuclear
      and CD34+ cell isolation) have on the number, viability and ex vivo expansion
      potential of PUCB cells. The results presented indicate the necessity of an open
      discussion on whether procedures used for handling the cells in PUCB banks can be
      extrapolated or not as such to the clinical use of ex vivo expanded PUCB.

PMID- 11293303
TI  - [The home health care experience in a model chronic, degenerative, genetic
      pathology: Huntington's disease].
AB  - Home assistance has recently received wide approval among the facilities provided
      to the individuals suffering from chronic-degenerative diseases. This mode of
      caring seems to offer both the opportunities to reduce costs and to allow the
      affected individual to live in a familiar environment. The increasing relevance
      of genetic diseases in the context of the National Health Service suggested the
      authors to analyze, by means of an ad hoc questionnaire, the experience of home
      assistance in a group of families with Huntington's Disease (HD). HD is a
      chronic, degenerative, genetic disease characterized by neurological and/or
      mental symptoms. The article underlines the peculiar and complex needs of
      individuals affected by genetic diseases and of their families.

PMID- 11293304
TI  - [Usefulness of online bibliographic research in biomedical research, with an
      application to the epidemiologic study of genetic osteopathy].
AB  - The bibliographic research online is an useful means of recovering information in
      all the subjects, particularly in the field of biomedicine. In fact, this
      instrument allows researchers to get information in a rapid, complete and up-to
      date way. The aim of the present review is to describe the usefulness of the
      bibliographical research online in the field of the genetic osteopathies. These
      are rare disorders: so, their own rarity makes the bibliographical research
      online necessary to carry out a large and effective comparison of experiences.
      The obtained results are amply reported in the manuscript. For instance, we
      verified that chondrodysplasias are the diseases most represented in the
      literature, while melorheostosis the disorder less mentioned. Moreover, we
      evidenced that some hereditary disorders of connective tissue, such as Marfan's
      syndrome, osteogenesis imperfecta and Ehlers-Danlos syndrome, are strongly
      influenced by race, sex and age.

PMID- 11293305
TI  - [Pharmaco-epidemiologic indicators for the analysis of drug consumption at the
      regional level].
AB  - The analysis of drug use is often limited to the description of per capita
      pharmaceutical expenditure. Differences that are observed in the comparison are
      attributable to the specific age and gender distribution of the compared
      populations, and to prescriptive behaviors of general practitioners. Aim of this
      paper is to analyze drug prescription in a local health unit of the Friuli
      Venezia Giulia region. In order to take into account differences in age
      distribution among health districts we used "weighted" populations. An in depth
      analysis has been carried out on antihypertensive drugs to evaluate differences
      in GPs' prescriptive behavior. Both the differences among districts in the level
      of drug use, and variability observed in antihypertensive use in the population,
      suggest that drug prescription might be partly inappropriate.

PMID- 11293306
TI  - [Bioethics and toxicology].
AB  - Human activity, involving nature and environment, alters the ecosystems in which
      we live; the question is whether this activity can be the source of risk and/or
      the origin of damages to human health. Risk assessment and risk management,
      connected with its protection, are not only a scientific and technical problem:
      hazards are real, but risks are social constructions. The role of toxicologists
      shows subjective features connected with different affiliations (industry,
      research, government); thus the assumptions and interpretations of risk
      assessment need to be integrated with wider psychological, social and political
      perspectives, in particular with ethical choices and values. Within public health
      personal subjectivities (genetic, biological and social) an adequate value should
      be given contrary to an abstract and collective entity which may erase and
      sacrifice subjectivities in favour of a statistical point of view. Public health
      should be considered as a whole of individual health conditions with regard to
      prevention, treatment and care.

PMID- 11293307
TI  - [Male breast tumors in railway engine drivers: investigation of 5 cases].
AB  - The paper describes the results of the investigation carried out on five cases of
      male breast tumours in railway engine drivers notified to the public Occupational
      Health Service of Florence in 1999. The aim was to evaluate the possibility of
      professional extremely low frequency electromagnetic fields (ELF) exposure
      etiology. The extent of this exposure is described with particular care to engine
      drivers, comparing the one measured in Italy with those reported in other
      countries.

PMID- 11293308
TI  - [Dialysis in Denmark].

PMID- 11293309
TI  - [Explanation of diabetic retinopathy. Current challenges and future
      perspectives].

PMID- 11293310
TI  - [Homocysteine and cardiovascular disease].
AB  - Treatment of highly increased plasma concentrations of homocysteine in patients
      with rare inborn errors of metabolism reduces their risk of vascular thromboses.
      Many, but not all, epidemiological studies show a relation between slightly
      increased plasma homocysteine and ischaemic cardiovascular disease. Folic acid
      supplements reduce plasma homocysteine. The results of ongoing studies of the
      effect of folic acid and other vitamins on the incidence of cardiovascular
      disease are expected within the next five years. The available data support the
      measurement of plasma homocysteine as a part of screening of patients with early
      and/or frequent vascular thromboses and a disparity between established risk
      factors and symptoms. Plasma homocysteine > 30 mumol/l in such patients should
      prompt a search for an inborn error of metabolism.

PMID- 11293311
TI  - [Is infection a pathogenetic factor in coronary heart disease?].
AB  - BACKGROUND: Several wellknown risk-factors can contribute to the development of
      coronary artery disease. A relatively new question is whether infection is also
      involved in the pathogenesis. Acute and/or chronic infections might affect
      initiation, progression and instability in coronary artery disease, as well as
      enhance development of restenosis and transplant atherosclerosis. In clinical
      studies it is possible to measure the amount of antibodies in blood samples,
      detect infectious agents in atheromatous lesions, and evaluate potential effects
      of antibiotic treatment. In animal models it is possible to investigate whether a
      direct infection can induce atheromatosis. MATERIAL AND METHODS: The aim of this
      article is to give an updated overview of clinical and experimental results and
      discuss potential consequences for the treatment of coronary artery disease.
      Possible cellular mechanisms will be presented. RESULTS: In conclusion, there is
      an association between coronary artery disease and infection with Chlamydia
      pneumoniae. Similar results are not obtained for infection with Helicobacter
      pylori. There is also an association between cytomegalovirus infection and
      development of restenosis and transplant atherosclerosis. However, a possible
      direct causal relationship is not fully established. Of special interest is
      whether antibiotic treatment can prevent acute cardiovascular events.
      INTERPRETATION: Primary prevention must still be targeted at conventional risk
      factors. However, in secondary prevention it can be valuable to identify
      subgroups of patients which may benefit from anti-infection treatment.

PMID- 11293312
TI  - [Resistant tuberculosis in Denmark].
AB  - INTRODUCTION: Increased rates of multidrug-resistant (MDR) tuberculosis (TB) has
      been reported from countries close to Denmark. We evaluated the incidence of drug
      resistance in Denmark in order to determine the magnitude of the problem.
      MATERIALS AND METHODS: Susceptibility testing was performed in isolates from
      85.4% of all notified patients during 1991-1998. Epidemiological information was
      retrieved from the mandatory notification forms. RESULTS: Total drug resistance
      remained largely constant, although a minor increase was observed in 1997-1998.
      Monoresistance was observed in 7.3% of the isolates. Among 3.6% polyresistant
      isolates, resistance to isoniazid and streptomycin accounted for 2.8%, whereas
      MDR accounted for 0.5%. The MDR strains displayed different restriction fragment
      length polymorphism (RFLP) patterns, and no matches were identified in the
      international MDR database. Drug resistance in untreated Danes and foreigners
      were 5.9% and 14.6%, respectively. Among Danes and foreigners with previous TB,
      6.2% and 22.7% had drug resistance, respectively. Increased drug resistance was
      found among untreated Danes aged 25-54 years mainly due to a single isoniazid-
      and streptomycin-resistant RFLP-cluster. Among all patients with isoniazid- and
      streptomycin-resistance, 77.0% had clustered strains. DISCUSSION: In conclusion,
      although drug resistance among untreated Danes was close to the rate estimated in
      good national programmes, close monitoring is needed in future years, as active
      transmission of isoniazid- and streptomycin-resistant Mycobacterium tuberculosis
      was demonstrated.

PMID- 11293313
TI  - [Benefit, effectiveness and cost of parasite investigations in the county of
      Copenhagen].
AB  - OBJECTIVE: To evaluate the cost and effectiveness of parasite investigations in
      our laboratory in order to restrict the number of specimens. METHODS: The
      analysis were performed retrospectively on 53,701 specimens submitted for cysts,
      ova, and larvae, 224 specimens for intestinal trophozoites, 1,888 cellophane tape
      impressions, 3,134 malaria smears, and 524 bronchial aspirates. RESULTS:
      Potentially pathogenic parasites were demonstrated in 3.2% of specimens examined
      for cysts, ova, and larvae, 6% examined for intestinal trophozoites, 16% for
      pinworm, 7% for malaria, and 9% for Pneumocystis. The cost of demonstrating a
      single infection with a pathogenic parasite was calculated to be DKK 6206 for
      cyst, ova, and larva specimens. This cost could be reduced considerably, if the
      examination of patients with acute diarrhoea, but without a history of travel was
      omitted. Similarly, the demonstration of trophozoites, pinworm, malaria and
      Pneumocystis in a person was calculated to be DKK 1122, DKK 526, DKK 2874 and DKK
      3716, respectively. Examination of three specimens for cysts, ova, and larvae
      showed 62-74% of the infections in the first sample. Two specimens increased the
      frequency of positive findings by 13-23% and three specimens by a further 9-12%.
      For the blood smears, 92% of the infections were demonstrated in the first
      sample. DISCUSSION: The analysis shows that to obtain an acceptable ratio between
      cost and diagnostic yield, the indication for the investigations should be
      tightened up. However, examination of three samples from each patient is
      necessary to exclude a parasitic infection.

PMID- 11293314
TI  - [Myocardial scintigraphy and coronary arteriography in patients with known or
      suspected stable angina pectoris].
AB  - INTRODUCTION: Myocardial perfusion imaging (MPI) demonstrates regional
      hypoperfusion, whereas coronary angiography shows anatomical stenoses in
      epicardial arteries. Both modalities are potentially relevant in patients with
      stable angina pectoris. MATERIALS AND METHODS: MPI was undertaken before
      angiography in 86 randomly selected patients with stable angina pectoris.
      RESULTS: Of 78 adequately stressed patients, MPI was normal in 28 (36%) and
      showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20
      patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and
      revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single
      vessel and 34 with multivessel disease). With angiography as reference, the
      sensitivity and specificity of MPI in the detection of coronary artery disease
      were 88% and 93%, respectively. DISCUSSION: Patients with stable angina pectoris
      and a normal MPI have a very low risk of cardiac events and do not usually
      require invasive investigation and therapy. Reversible ischaemia and irreversible
      ischaemia with viable tissue call for coronary revascularisation.

PMID- 11293315
TI  - [Users' experiences with modern hearing aids. An audit].
AB  - INTRODUCTION: The aim of the study was to evaluate satisfaction with use and
      manipulation of hearing aids (HA), and to compare these parameters for analogue
      (A-HA), programmable (P-HA), and digital signal processing aids (DSP-HA). METHOD:
      An audit was made of data on users' experiences, as indicated in a questionnaire
      posted 3-4 months after the HA fitting. MATERIAL: Questionnaires were posted to
      18,702 persons, who, during the period 1997-1999, had been provided with a HA at
      a median age of 77 years (range 18-98), 41.8% of whom were men, and 58.2% women.
      Responses were returned by 12,866 (68.8%), and, as there were no differences
      between the respondents and non-respondents with respect to age, gender, and
      distribution of HA type, the responses were considered representative. RESULTS:
      According to the replies, 71.5% were very satisfied/satisfied with their HA; 89%
      used the instrument daily/weekly, and 75% were able to manipulate the HA without
      problems. However, 10.7-12.7% said they never used the fitted HA. A significantly
      higher proportion were satisfied with A-HAs as compared to P-HAs and DSP-HAs,
      whereas there was no significant difference in use as a function of type. A
      significantly higher number of the users fitted with a DSP-HA could manipulate
      them, but 36.5% of these needed follow-up in contrast to 25.5% fitted with a P
      HA, and 21.6% fitted with an A-HA. A significantly smaller proportion of the
      elderly were able to manipulate the HA. CONCLUSION: The users of modern HAs are
      satisfied with them, use them, and most are able to manipulate the HA without
      problems. The new technology has raised unrealistic expectations in the users,
      and the DSP-HAs account for larger costs to the national health services, because
      they are more expensive and the need for staff resources is greater.

PMID- 11293316
TI  - [Quality assurance of hemodialysis. Results after five years].

PMID- 11293317
TI  - [Brain metastases from colorectal cancer].
AB  - Brain metastases from colorectal cancer are rare. The prognosis for patients with
      even a single resectable brain metastasis is poor. A case of surgically treated
      cerebral metastasis from a rectal carcinoma is reported. The brain tumour was
      radically resected. However, cerebral, as well as extracerebral, disease recurred
      12 months after diagnosis. Surgical removal of colorectal metastatic brain
      lesions in selected cases results in a longer survival time.

PMID- 11293318
TI  - [Picture of the month: facial paralysis and borreliosis].

PMID- 11293319
TI  - [Val-HeFT-Valsartan Heart Failure Trial].

PMID- 11293320
TI  - [Control of biomedical trials].

PMID- 11293321
TI  - [The epidemic (of smoking) no one dares to see].

PMID- 11293322
TI  - [Can ultrasound substitute arteriography for visualization of leg
      arteriosclerosis?].

PMID- 11293323
TI  - Genetic linkage of nuclear morphology of mouse lung tumors to the Kras-2 locus.
AB  - Search for quantitative trait loci (QTLs) has been successful in the past decade
      by revealing numerous susceptibility to lung cancer loci in specially designed
      experimental crosses in mice. Although qualitative aspects of lung tumorigenesis
      are also genetically controlled, no loci affecting such traits have so far been
      identified. We analyzed a series of lung tumors derived from various inbred and
      recombinant congenic strains and F2 crosses for two histological characteristics:
      nuclear cytoplasmic invaginations (NCIs) and lymphocytic infiltration (LI) and
      performed linkage analysis. A significant linkage of the Kras-2 locus with
      presence or absence of NCI was detected. The implications of this linkage as well
      as the relationships between NCI, LI, tumor size and Kras-2 alleles are
      discussed.

PMID- 11293324
TI  - Butylated hydroxytoluene (BHT) induction of pulmonary inflammation: a role in
      tumor promotion.
AB  - Chronic pulmonary inflammatory diseases predispose towards lung cancer by unknown
      mechanisms. Butylated hydroxytoluene (BHT) administration to mice causes lung
      injury and a subsequent inflammatory response, and when administered chronically
      to certain inbred strains following carcinogen treatment, increases lung tumor
      multiplicity. We hypothesize that inflammation promotes lung tumor growth in this
      model system and have begun to examine this hypothesis by assessing inflammatory
      parameters in inbred strains that vary in their susceptibility to promotion.
      Positive correlations were found between susceptibilities to tumor promotion and
      BHT induction of alveolar macrophage and lymphocyte infiltration into alveolar
      airspaces, and increased vascular permeability (P < .03, P < .04, and P < .005,
      respectively). The amounts of pulmonary cyclooxygenase (COX)-1 and COX-2 did not
      strongly correlate with promotion. Because persistent elevation of macrophage
      content is the hallmark of a chronic inflammatory response, the alveolar
      macrophage population was depleted by adding chlorine to the drinking water prior
      to carcinogenesis. This treatment reduced lung tumor multiplicity following 2
      stage carcinogenesis (P < .05). These correlations between inflammatory and
      tumorigenic responses to BHT, along with decreased tumorigenesis after macrophage
      depletion, are consistent with a role of inflammation in promotion. Inflammatory
      mediators may provide targets for early diagnosis and chemoprevention.

PMID- 11293325
TI  - Detection of differentially expressed genes in mouse lung adenocarcinomas.
AB  - Increasing evidence suggests that altered gene expression is associated with the
      induction and maintenance of malignancy in various organs including mouse lung
      adenocarcinomas. A competitive cDNA library screening (CCLS) was used to examine
      gene expression in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung
      adenocarcinomas from (C3H/HeJ x A/J])F1 mice. Comparisons of RNA expression in
      lung adenocarcinomas to those of normal surrounding lung tissue revealed altered
      expression in 220 clones from more than 50,000 clones screened. Fifty clones were
      selected for quantitative reverse transcriptase-polymerase chain reaction (PCR)
      analysis to verify altered expression. PCR primers were designed based on partial
      sequence analysis of the clones. Twenty-two clones were found to be
      differentially expressed in lung adenocarcinomas compared with normal lungs.
      GenBank database analysis showed that 14 of the 22 clones were homologous with
      known genes, whereas 8 clones contained novel sequences. Thirteen clones were
      down regulated in tumors compared to normal lung tissues, and 9 were
      overexpressed. The clones underexpressed or absent include adipocyte p27,
      carbonic anhydrase III, carbonyl reductase, cytochrome CYP2E1, skelemin, myosin,
      major urinary protein, and contrapsin. Overexpressed clones include Bruton's
      tyrosine kinase, cyclin D3, poly(A)-binding protein, alpha-fetoprotein,
      transferrin, and mouse B2 family repetitive sequence. Further examination of
      biologic implications of the differentially expressed genes in lung
      adenocarcinomas is necessary to understand their role(s) in mouse lung
      carcinogenesis.

PMID- 11293326
TI  - Defective gap junctional intercellular communication in lung cancer: loss of an
      important mediator of tissue homeostasis and phenotypic regulation.
AB  - Gap junctions provide direct pathways for the exchange of molecules and ions
      between neighboring cells, a process known as gap junctional intercellular
      communication (GJIC). This GJIC is important for homeostasis and regulation of
      mitosis, differentiation, and apoptosis. Gap junctions are present in lung airway
      and alveolar epithelial cells and, in addition to the above roles, might
      coordinate ciliary beating and surfactant secretion. GJIC is decreased in human
      and mouse lung carcinoma cells because of reduced expression of the gap junction
      protein, connexin43 (Cx43), and defects in signal transduction pathways that
      mediate Cx43 function. This reduced GJIC is important in the behavior of lung
      carcinoma cells because forced expression of Cx43 in lung carcinoma cells
      inhibits their growth and tumorigenicity. In this report, we summarize our
      studies on the role of GJIC in lung neoplasia.

PMID- 11293327
TI  - The effects of a binary mixture of benzo(a)pyrene and 7H-dibenzo(c,g)carbazole on
      lung tumors and K-ras oncogene mutations in strain A/J mice.
AB  - Polycyclic aromatic hydrocarbons (PAH) and N-heterocyclic aromatic hydrocarbons
      (NHA) are environmental pollutants formed during the incomplete combustion of
      organic materials. Benzo(a)pyrene (BaP) and 7H-dibenzo(c,g)carbazole (DBC) are
      well-characterized representatives of the PAH and NHA classes of compunds,
      respectively. Both are demonstrated carcinogens that frequently co-occur in
      environmental mixtures. This preliminary study was conducted to investigate the
      effects of a binary mixture of BaP and DBC on lung carcinogenicity in the strain
      A/J mouse as manifested by tumor development and mutations in the K-ras gene.
      Male A/J mice were administered the following single intraperitoneal dose (mg/kg)
      combinations of BaP and DBC dissolved in a 0.2-mL volume of tricaprylin--10
      DBC:10 BaP; 2 DBC:10 BaP; 2 DBC:100 BaP; and 10 DBC: 100 BaP, and each of the
      compounds alone at the same doses. Mice were sacrificed 8 months after carcinogen
      treatment and lung tumor multiplicity and K-ras mutations determined (high-dose
      combination). The combination of DBC and BaP produced fewer tumors than the sum
      of all tumors produced by each compound acting alone. The frequency of tumors
      with K-ras mutations was also less in a sample of the 10 DBC:100 BaP treatment
      group than in the same-dose, single compound-treated animals. The dominant
      mutations produced by BaP and DBC were expressed in tumors from animals treated
      with the mixture.

PMID- 11293328
TI  - Alternative splicing of the K-ras gene in mouse tissues and cell lines.
AB  - The mRNA from the K-ras protooncogene is alternatively spliced into 2
      transcripts, K-ras4A and K-ras4B, which possess 2 alternative fourth coding
      exons. In the present study, expression of K-ras4A and K-ras4B transcripts in 8
      organs, including heart, brain, spleen, lung, liver, skeletal muscle, kidney, and
      testis, from BALB/c mice were determined by Northern blot hybridization. K-ras4B,
      observed in all organs, accounted for approximately 90% to 99% of total K-ras
      mRNA. K-ras4A was detected only in lung, liver, and kidney. In addition, K-ras
      expression in lungs and K-ras4A/K-ras4B ratios in lung, liver, spleen, and kidney
      from A/J, BALB/c, C3H/HeJ, and C57BL/6J mice were determined. A/J lungs expressed
      K-ras mRNA 2-fold higher than C3H/HeJ or C57BL/6J lungs, whereas K-ras mRNA
      expression in BALB/c lungs was intermediate. Higher percentages of K-ras4A mRNA
      were found in lungs and kidneys from A/J and BALB/c mice, as compared with those
      from C3H/HeJ and C57BL/6J mice. Levels of K-ras4A and K-ras4B mRNAs were also
      examined in 20 NIH 3T3 cell lines transformed by DNA from spontaneous A/J mouse
      lung tumors. K-ras4A was expressed 2- to 3-fold higher in these cell lines than
      in nontransformed NIH 3T3 cells and in C10 cell lines. These results suggest
      that: (1) there may be functional differences between the protein encoded by K
      ras4A and that encoded by K-ras4B in each tissue type, and in tumor cells; and
      (2) K-ras mRNA expression and K-ras4A/K-ras4B ratios detected in lung tissues
      from different strains of mice correlate with susceptibility to tumor induction.

PMID- 11293329
TI  - Regulation of the Raf kinase by phosphorylation.
AB  - The Raf serine/threonine kinase plays an essential role to relay intracellular
      signals from the protooncogene Ras to activation of the mitogen-activated protein
      kinase (MAPK) cascade. The Raf kinase family consists of C-Raf (Raf-1), B-Raf,
      and A-Raf. Extensive efforts have been made in the last decade to study Raf
      regulation; however, precise molecular mechanism for Raf activation is still not
      fully understood. In this report, we discuss the current model of Raf regulation.
      Here we also report our recent findings that phosphorylation of Thr598 and
      Ser601, which lie between kinase subdomains VII and VIII, is essential for B-Raf
      activation by Ras. Substitution of these residues to alanine (B-RafAA) abolished
      Ras-induced B-Raf activation, without altering the association of B-Raf with
      other signaling proteins. Phosphopeptide mapping and immunoblotting with
      phosphospecific antibodies, which selectively recognize Thr598 and Ser601,
      phosphorylated B-Raf, confirmed that Thr598 and Ser601 are in vivo
      phosphorylation sites induced by Ras. Further, replacement of these two sites
      with acidic residues (B-RafED) renders B-Raf constitutively active. Consistent
      with these data, B-RafAA and B-RafED exhibited diminished and enhanced ability,
      respectively, to stimulate extracellular signal-regulated kinase (ERK) and Elk
      dependent transcription. Moreover, functional studies revealed that B-RafED was
      able to promote NIH3T3 cell transformation and PC12 cell differentiation. Because
      Thr598 and Ser601 are conserved in all Raf family members, from Caenorhabditis
      elegans to mammals, we propose that phosphorylation of these two residues may be
      a general mechanism for Raf activation.

PMID- 11293330
TI  - Inactivation of both Rb and p53 pathways in mouse lung epithelial cell lines.
AB  - Aberrant expression of key cell cycle regulatory genes is essential for the
      immortalization and transformation of cells in vitro. We examined 20 mouse lung
      epithelial cell lines (2 nontumorigenic, 5 nonmetastatic, and 13 metastatic) for
      mutations or alterations in the expression of key components of the Rb pathway
      (pRb and p16INK4a) and the p53 pathway (p53 and p19ARF). Seven cell lines had a
      mutation in exons 5 to 8 of p53. p19ARF was inactivated in the remaining 13 cell
      lines, primarily by homozygous deletion. Rb expression was present and unaltered
      in all cell lines, with both phosphorylated and unphosphorylated protein forms
      detectable. p16INK4a transcripts were undetectable in all cell lines tested
      except LM1. Loss of p16INK4a expression was a result of homozygous deletion in 11
      out of 20 lung cell lines and promoter-exon 1 hypermethylation in 6 out of the
      remaining 8 cell lines. Other related components that were examined in this study
      included p21WAF1 and cyclin D1. Compared to normal lung tissue, p21WAF1
      expression levels were reduced or undetectable in all cell lines, which did not
      correlate with loss of p53 function, but did correlate with inactivation of
      either p53 or p19ARF. Although cyclin D1 expression was variable between cell
      lines, transcript levels were decreased by at least 50% in the nontumorigenic
      lines C10 and E10 compared to the tumorigenic cell lines. These results
      demonstrate mutually exclusive relationships between p53 and p19ARF and between
      Rb and p16INK4a, but perhaps not between cyclin D1 and p16INK4a, and further
      describe the nature of involvement of both pathways in mouse lung tumorigenesis.

PMID- 11293331
TI  - Chemoprevention of lung cancer by isothiocyanates and their conjugates in A/J
      mouse.
AB  - The discovery of dietary-related compounds with potential to inhibit lung cancer
      may present promising and practical approaches for reducing the risk of lung
      cancer caused by smoking. To this end, we have conducted mechanism-based
      bioassays in A/J mice over the years to screen compounds, particularly
      isothiocyanates (ITCs) in the crucifer family, and studied their modes of action
      against lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK), a nicotine-derived lung carcinogen. These studies have shown that
      A/J mice serve as a practical and useful model for the study of lung cancer
      prevention. The studies described here illustrate the value of using the A/J
      mouse model in the bioassays and the structural-activity relationship,
      metabolism, and mechanism investigations. One of the important features of the
      A/J mouse model is that a single dose of NNK induces a significant number of lung
      tumors within 16 weeks. This feature offers a prerequisite for in vivo screening
      as well as for dissecting the initiation or the postinitiation effect of ITCs and
      their conjugates during lung tumor development. Our recent bioassays in A/J mice
      demonstrate that ITC conjugates are versatile chemopreventive agents capable of
      inhibiting NNK-induced lung tumorigenesis during both the initiation and the
      postinitiation phases. These findings are of importance, considering the
      potential of these agents as chemopreventive agents for lung cancer in smokers
      and ex-smokers.

PMID- 11293332
TI  - Awful offal.

PMID- 11293333
TI  - Vanderbilt Morning Report.

PMID- 11293334
TI  - Tuberculosis update.

PMID- 11293335
TI  - The untapped potential of electronic medical records. Pt. 1--Road-testing the
      promises of EMR technology.

PMID- 11293336
TI  - Loss prevention case of the month. All bases must be covered.

PMID- 11293337
TI  - Health Policy Report. Incrementalism--climbing Mount Everest one step at a time.

PMID- 11293338
TI  - Why genetic competencies in public health and preventive medicine?

PMID- 11293339
TI  - Peripartum cardiomyopathy: echocardiogram to predict prognosis.
AB  - Peripartum cardiomyopathy is an uncommon complication of human pregnancy that
      threatens both the mother and fetus with maternal congestive heart failure.
      Clinicians must be aware of this problem in order to provide prompt diagnosis and
      effective treatment that will insure a favorable return of normal left
      ventricular function.

PMID- 11293340
TI  - Immunization status of 2-year-old children, year 2000 survey results.
AB  - Immunization rates among Tennessee's 2-year-olds remain at high levels, and
      disease remains at historically low levels. The completion rates have remained
      relatively stable for the past three years, although there has been an
      equalization of rates among the regions. The portion of the TennCare population
      receiving all their vaccines in the private setting will continue to require
      additional resources to sustain the improvements noted in this survey. Other
      children who have been identified as being at increased risk for incompletion are
      children starting their vaccine series past age 120 days and children with two or
      more older siblings. The Immunization Program has embarked on collaboration with
      the TennCare managed care organizations (MCOs) to electronically exchange
      immunization data with the Immunization Registry. This will eventually enable
      physicians, MCOs, and health department personnel to identify high-risk children
      and children who are behind in their immunization series for more intensive
      follow-up. The goal of 90% of all children being completely immunized by their
      second birthday is within our reach, as demonstrated by the dramatic increases in
      immunization levels in the past ten years. To reach that goal will require that
      we in the medical community, public and private, continue to use those strategies
      that have worked while developing new strategies that continue the progress.

PMID- 11293341
TI  - [New version of the Helsinki Declaration].

PMID- 11293342
TI  - [Where to treat extremely premature infants?].

PMID- 11293343
TI  - [Patients in Norwegian intensive care units].

PMID- 11293344
TI  - [We are fatter and fatter--but is the health threatened?].

PMID- 11293345
TI  - [Prevalence of obesity among persons aged 40-42 years in two periods].
AB  - BACKGROUND: The prevalence of obesity is increasing. MATERIAL AND METHODS:
      Cardiovascular screening among persons 40-42 years has been carried out since
      1985 in all but one of the 19 Norwegian counties. In eight counties, screening
      was carried out both in 1994-96 and 1997-99. RESULTS: The prevalence of obesity
      (body mass index > or = 30 kg/m2) in the eight counties increased from 9.6% in
      men and 8.8% in women in 1994-96 to 14.0% and 11.6% in 1997-99. The relative
      increase was on the whole the same in all subgroups of the study population.
      There were strong cross-sectional relationships between lifestyle factors,
      general health, length of education and obesity. Changes in the distribution of
      these factors between the two periods did not at all explain the increased
      prevalence of obesity. INTERPRETATION: The prevalence of obesity is increasing in
      practically all segments of the population.

PMID- 11293346
TI  - [Height, weight and body mass index measured among men born 1967-80].
AB  - BACKGROUND: Statistics Norway has published data on the average height of
      conscripts since 1910. Average height of men was 171.4 cm in 1920 and increased
      by 7.3 cm to 178.7 cm in 1970. Over the last 30 years, average height has
      increased only 1 cm, to 179.7 cm in 2000. The concern now is the fact that the
      average body weight of conscripts has been increasing. To monitor this
      development, statistics, based on BMI would be warranted. MATERIAL AND METHODS:
      The basis for such a statistics is explored in a study including all men born
      1967-1980 known to the Norwegian central population registry as of December 1997;
      a total of 475,076 men. Data from the medical examinations for military service
      were obtained from the National Service Administration for 413,051 (86.9%). Of
      these men 400,297 (96.9%) were born in Norway, 12,754 abroad. RESULTS: The
      proportion of men born in Norway who were not examined averaged 6.4%. This
      percentage was much the same for each cohort. The reasons for being exempted from
      examination were the same, this indicates that there was no difference in
      selection bias between cohorts. No data were available for the assessment of the
      reliability and validity of the measurements. Nevertheless, trends in average
      height, weight and BMI give a clear picture of changes that have occurred.
      INTERPRETATION: Provided that validity of the measurements can be secured, it is
      concluded that examinations for military service can offer useful data for a
      health index on the growth and development of young men.

PMID- 11293347
TI  - [Thalassemia and sickle-cell disease in Norway].
AB  - BACKGROUND: Thalassemia is common in the Mediterranean countries, the Middle
      East, parts of India and South East Asia, with the prevalence of mutations
      reported to be 2.5-15%. Sickle-cell anaemia is endemic primarily in central parts
      of Africa, but it also appears in the thalassaemia areas. The purpose of this
      study was to establish the prevalence of beta-thalassaemia, alfa-thalassaemia and
      sickle-cell anaemia in Norway. MATERIAL AND METHODS: A questionnaire was sent to
      149 departments of paediatrics, gynaecology and medicine in Norway. We asked for
      numbers registered in 1996 and 1997 of beta-thalassaemia and alfa-thalassaemia
      with subgroups, and sickle-cell anaemia. RESULTS: The number of patients with
      thalassaemia was 44 (0.001%) in 1996 and 48 in 1997. In 1996 there were 28
      patients with beta-thalassaemia minor, three with intermediary and five major,
      and six patients with alfa-thalassaemia minor and one with major. In 1996, ten
      patients were registered with sickle-cell anaemia; in 1997, fifteen patients.
      INTERPRETATION: The numbers of patients with thalassaemia major or sickle-cell
      anaemia probably reflect the true prevalence of these diseases. However, for
      thalassaemia minor and sickle-cell anaemia trait the numbers appear to be too
      low, as most of these patients do not contact a hospital. The appearance of these
      diseases in Norway is closely related to immigration from endemic areas.

PMID- 11293348
TI  - [Activity registration in intensive care units].
AB  - Intensive care treatment is expensive and its capacity is limited. The population
      of elderly patients with greater need for intensive care increases. It has become
      more important to evaluate the use of intensive care resources and to compare it
      with the results of treatment. Diagnoses do not provide a satisfactory
      description of the stay in the intensive care unit. Scoring systems for severity
      of illness and for resource needs are therefore of great value. The Norwegian
      Board of Health has requested all intensive care units in Norway to describe
      their activities by scoring systems for severity of illness, SAPS II (Simplified
      Acute Physiology Score II) and for use of resources NEMS (Nine Equivalents of
      Nursing Manpower Use Score). The systems are generally well recognised, easy to
      learn and not time-consuming. Through SAPS II and NEMS it is possible to compare
      results of treatment and use of resources across intensive care units or against
      a standard.

PMID- 11293349
TI  - [Experiences with scoring systems SAPS II and NEMS for registration of activities
      in an intensive care unit].
AB  - BACKGROUND: Intensive care is highly expensive, hence the requirement of
      efficient use of resources calls for evaluation of the severity of disease or
      injury for each individual patient, so that management may be optimised. MATERIAL
      AND METHODS: At Ullevaal University Hospital, two different scoring systems have
      been used since 1996: SAPS II (Simplified Acute Physiology Score) for severity of
      illness and NEMS (Nine Equivalents of Nursing Manpower Use Score) for assessment
      of resource utilisation. RESULTS: A significant relationship between severity of
      illness and mortality was found. Length of stay in ICU correlated with increasing
      SAPS II score in the range 0 to 50, but at higher scores no relationship was
      found. Patients with trauma and cardiovascular surgical patients used most of the
      resources. 79% of total NEMS score consisted of vital signs monitoring,
      intravenous drug medication and mechanical ventilation of the patients.
      INTERPRETATION: SAPS II and NEMS scoring systems provide useful information
      needed in the assessment of patient care in the ICU and are helpful in the
      documentation of financial and medical resource needs.

PMID- 11293350
TI  - [Organization and management of Norwegian intensive care units].
AB  - BACKGROUND: A survey of organisational and managerial aspects in Norwegian
      intensive care units (ICU) was made six months after Standards for Intensive
      Care, a document setting out guidelines for the organisation and management of
      intensive care units, had been issued by the Norwegian Medical Association to
      Norwegian hospitals. MATERIAL AND METHODS: 298 questionnaires were sent to
      hospital managers and heads of clinical departments in 58 Norwegian hospitals.
      RESULTS: The overall response rate was 77%. 60% of the respondents had heard
      about Standards, 44% had read them, 15% used them. The majority of ICUs were run
      by the Department of Anaesthesia. 75% answered that the admitting department had
      the overall responsibility for the individual patient; 23% of respondents claimed
      that the ICU doctor was responsible. More than half of these worked in secondary
      and tertiary care hospitals. INTERPRETATION: Standards of Intensive Care is
      poorly known and read by less than half of the respondents. Only a few have
      started to implement them. Some uncertainty about patient responsibility may
      exist particularly in secondary and tertiary care hospitals. There seems to be a
      need for better role clarification and definitions of responsibility for all
      participants in intensive care, with more focus on organisational and managerial
      aspects.

PMID- 11293351
TI  - [Activities and staffing in intensive care units in Norway--still need of better
      registration].
AB  - BACKGROUND: Standards in Intensive Care Medicine were approved by the Board of
      the Norwegian Medical Association in 1997. Their purpose is to clarify issues of
      responsibility, accountability and management in intensive care units. It also
      gives recommendations on management, staffing, education and resources. MATERIAL
      AND METHODS: In order to obtain a reference point for any future assessment of
      the impact of the Standards document, a survey was carried out, addressing work
      load, medical staff, and questions of accountability, responsibility and
      cooperation. RESULTS: 16 hospitals responded (76%). The results seem to indicate
      that medical staff in relation to work load is smaller than recommended. It also
      seems that junior doctors only to a small extent are present in the intensive
      care units during ordinary working hours, and consequently have little
      opportunity to learn from working with experienced colleagues. However, both
      conclusions, especially the first one, are not entirely reliable, as close
      examination of the answers indicate that important concepts concerning the
      description of work load and staffing are poorly defined, and that the monitoring
      of work load is insufficient. INTERPRETATION: It is concluded that staffing and
      work load in intensive care units are still insufficiently defined and monitored.
      The training environment for specialists is not optimal.

PMID- 11293352
TI  - [Magnetic resonance arthrography of the hip joint in patients with suspected
      rupture of labrum acetabulare].
AB  - INTRODUCTION: MR arthrography by direct joint puncture and instillation of
      contrast medium is a minimally-invasive diagnostic technique in patients with
      suspected acetabular labral tear. The joint is distended, and the intraarticular
      structures are well separated. MATERIAL AND METHODS: 31 patients with chronic hip
      joint pain underwent MR arthrography by direct joint puncture and instillation of
      diluted gadolinium to evaluate the glenoid labrum. RESULTS: The glenoid labrum
      was seen in all patients. Labral tear was found in ten patients. Two of these
      underwent arthroscopy, and the tears were verified. We also found other causes of
      hip pain. One patient with villonodular synovitis at MR arthrography was verified
      at arthroscopy. INTERPRETATION: MR arthrography is a promising diagnostic
      technique for evaluating the acetabular labrum.

PMID- 11293353
TI  - [Are the newer antihypertensive agents better and more effective than
      diuretics?].
AB  - BACKGROUND: In recent years, the expenses for medical antihypertensive therapy
      have increased considerably, the main reason being the switchover to newer and
      more expensive antihypertensive drugs. RESULTS: Several recent studies which have
      compared the efficacy of the older, conventional drugs (thiazid diuretics and
      beta-blockers) with the newer agents (calcium blockers, angiotensin-converting
      enzyme (ACE) inhibitors), have shown that they are almost equipotent with regard
      to effects on blood pressure, morbidity and mortality. At lower doses, the
      metabolic effects of thiazide diuretics are minimal and probably without clinical
      significance, and the risk of developing diabetes mellitus type 2 does not seem
      to be increased. INTERPRETATION: The cheaper thiazide diuretics are still
      valuable drugs in the treatment of hypertension. If more than one agent is
      necessary to reduce blood pressure to the desired level, they can be combined
      with other antihypertensive agents.

PMID- 11293354
TI  - [Anatomist, pathologist and philanthropist].
AB  - Fredrik Georg Gade (1855-1933) was born in Bergen as the eldest son of a merchant
      and politician. He graduated from the University of Oslo in 1880. After clinical
      residency and training in anatomy and pathology at the National Hospital in Oslo,
      he worked in several of the most outstanding medical research institutions in
      Continental Europe, including the institutes of Robert Koch and Carl Friedlander
      in Berlin, Carl Weigert in Frankfurt, the pathologists and anatomists Victor
      Cornil, Louis-Antoine Ranvier and Louis Charles Malassez in Paris. Gade was
      associate professor (prosector) of anatomy in Oslo from 1897 to 1906 and also the
      editor of the Norwegian Medical Journal (Norsk Magazin for Laegevidenskaben). He
      was also one of the pioneers of cancer statistics in Norway. In addition to his
      scientific publications, he wrote extensively on political and cultural issues.
      Struck by serious illness he donated most of his family fortune to establish an
      institute for pathology in his home town Bergen, which opened in 1912 under the
      name Dr. med. F.G. Gades Pathologiske institutt. It later became one of the
      pillars of the Medical Faculty when the University of Bergen was established in
      1946 (now: The Gade Institute, University of Bergen).

PMID- 11293355
TI  - [Use of paracetamol to children].

PMID- 11293356
TI  - [Treatment of extremely premature infants--which limits and what problems?].
AB  - In Norway about 300 babies with a birthweight of 500-999 grams and 200 with a
      gestational age of 24-27 weeks are born annually. This gives a total of 320-330
      babies who come under the definition of extreme prematurity. Obstetric care is
      important in order to avoid premature birth, or, when premature birth is
      unavoidable, to find the optimal time and place for delivery. There is ongoing
      discussion of what constitutes reasonable lower limits for offering life support.
      The survival rate for babies born before 24 gestational weeks is low and the risk
      of serious neurological damage high. The risk of severe lung disease is reduced
      with pre- and postnatal treatment with corticosteroids and postnatal treatment
      with surfactant, but excessive corticosteroid treatment may possibly increase the
      risk of neurological damage. Despite major recent progress in the treatment of
      the preterm baby, significant understanding of why disabilities occur is lacking.

PMID- 11293357
TI  - [Health problems among immigrant children in Norway].
AB  - BACKGROUND: There are approximately 54,500 immigrant children (< 16 years) in
      Norway, half of them from non-western countries. METHODS: The authors present an
      overview of different health problems that are more frequent in the migration
      population than in the general Norwegian population. RESULTS AND INTERPRETATION:
      Psychological problems are very frequent among immigrant children from war areas,
      and a special therapy programme should be designed for this group. A broad
      spectrum of diseases that are uncommon among Norwegians, are present in the
      migrant population, such as sickle cell disease, thalassaemia, malaria, typhoid
      fever and tuberculosis. Doctors dealing with migrant children should learn how to
      diagnose and treat these diseases. Iron deficiency and vitamin D deficiency are
      also prevalent among immigrant children. As many as 65 children with nutritional
      rickets have been treated at Norwegian hospitals in 1998 and 1999, 54 of them
      with an immigrant background. This demonstrates the need for a new programme
      against nutritional rickets in Norway.

PMID- 11293358
TI  - [How to stimulate health behavior?].

PMID- 11293359
TI  - [Should treatment of infants with very low birth weight be centralized?].

PMID- 11293360
TI  - [Zyban in smoking cessation--where is medical ethics?].

PMID- 11293361
TI  - [Zyban and medical ethics].

PMID- 11293362
TI  - [Three primary stents in advanced esophageal cancer].

PMID- 11293363
TI  - [Mammography as screening method].

PMID- 11293364
TI  - Coping and illness cognitions: chronic fatigue syndrome.
AB  - The chronic fatigue syndrome (CFS) is described, and research on coping with this
      illness reviewed and analysed. CFS is a severely disabling illness of unknown
      etiology, which has occurred in epidemic forms all over the world. However, the
      number of sufferers has dramatically increased over previous years. The
      heterogeneous symptomatology of CFS was reviewed, and diagnostic criteria were
      discussed. The difficulty in establishing causality was emphasized. An
      interaction of factors appears most likely to be associated with illness onset
      and maintenance. As the mediating factor could be sufferers' coping behavior, the
      existing coping literature was reviewed. There might be an association between
      coping and physical and psychological well-being. Finally, recommendations are
      made for longitudinal research on coping and coping effectiveness, and for the
      development of therapeutic interventions.

PMID- 11293365
TI  - Revictimization rates and method variance: a meta-analysis.
AB  - The present meta-analytic review examined revictimization rates and sources of
      variance among rates provided by 19 empirical studies of adult females. In this
      review, revictimization refers to the occurrence of at least one incident of
      childhood sexual abuse followed by a subsequent incident of adult sexual
      victimization. Studies were included in the review if they provided rates of
      revictimization and had a comparison sample of nonrevictimized women. The overall
      effect size for revictimization was .59, a moderate effect, suggesting a definite
      relationship between childhood victimization and adult victimization experiences.
      The overall effect size was heterogeneous and various study characteristics and
      definition issues were examined to determine their effect on revictimization
      rates. The most striking, although not surprising finding, was that studies in
      which more inclusive definitions of abuse were utilized yielded smaller effect
      sizes than studies that used more restrictive definitions of abuse. Studies that
      examine victimization or revictimization are often concerned with learning more
      about the phenomenon with the expectation that by understanding the underlying
      mechanism, prevention and treatment can be better focused. The interpretation
      given to results from past and future studies should take into account those
      factors found to influence estimations of revictimization rates.

PMID- 11293366
TI  - Developing interventions for chronically ill patients: is coping a helpful
      concept?
AB  - In this review, the role of coping in the development of psychosocial
      interventions for chronically ill patients is discussed. After summarizing the
      theoretical issues involved in the translation of the coping concept into an
      intervention, a review is undertaken of 35 studies concerned with the impact of
      interventions aimed at improving coping on patients' quality of life. These
      studies concern seven different chronic disease types (AIDS, asthma, cancer,
      cardiovascular diseases, chronic pain, diabetes, and rheumatoid arthritis) and
      show explicit consideration of attempts to manage illness in terms of coping to
      be rare. Many studies nevertheless address the equivalent of coping, namely
      behaviors and/or cognitions intended to deal with an illness situation appraised
      as stressful. The results of these studies are encouraging, although largely
      limited to the improvement of one or two particular coping strategies and problem
      focused strategies in particular. It is argued that in order to expand on these
      initially positive findings, greater and more explicit consideration should be
      given to the potential of the coping concept for intervention with the
      chronically ill. The appraisal of stressful situations, the use of coping
      resources, and the strategic application of particular coping strategies should,
      for example, be given more careful consideration.

PMID- 11293367
TI  - Why does schizophrenia develop at late adolescence?
AB  - Schizophrenia is one of the most researched, yet still one of the least
      understood, of the mental disorders. One key area that remains comparatively
      neglected is the fact that schizophrenia typically develops at late adolescence.
      In common with people with psychotic disorders, around 25% of normal teenagers
      also report finding adolescence very distressing, and a substantial empirical
      literature shows that certain characteristics typical of adolescence such as
      conflicted family relationships, grandiosity, egocentrism, and magical ideation
      bear a distinct resemblance to phenomena seen in psychotic disorders. Indeed,
      such phenomena, as might be judged prodromal or symptomatic in first-onset
      schizophrenia, have been shown to be remarkably common in normal adolescents,
      generally in about 50% of samples. Furthermore, prodromal-like signs in normal
      adolescents appear to be functionally linked to psychological development. For
      most adolescents, such phenomena pass with successful psychological development.
      It is proposed that psychosis in late adolescence is a consequence of severe
      disruption in this normally difficult psychological maturational process in
      vulnerable individuals, and explanations are offered as to why and how this comes
      about. It is suggested that problems either in reaching psychological maturity
      with regard to parents or in bonding to peers or both, may lead to crucial self
      construction difficulties, and that psychosis emerges out of such "blocked
      adolescence." This approach proposes therapeutic interventions that enable
      professional services to side with both parents and clients simultaneously, and
      is normalizing and stigma-free.

PMID- 11293368
TI  - Remembering and reporting by children: the influence of cues and props.
AB  - Until recently nonverbal props received little experimental attention in spite of
      the wide use of props such as toys and drawing in child clinical contexts. This
      article reviews research investigating the effectiveness of props as means of
      facilitating children's recall and reporting of past events. In the first
      section, developmental and theoretical considerations influencing effectiveness
      of various kinds of props as aids to the retrieval and communication of
      information are outlined. Thereafter, findings of empirical research are reviewed
      for real props from the event, toys including dolls, drawing, context
      reinstatement, and photographs. Research findings suggest that a range of factors
      influence the extent to which props facilitate children's reports of past events,
      including specificity of the information provided by the prop, the way the prop
      is presented during the interview, delay between the event and interview and,
      critical to these factors, the age of the child. Areas requiring future
      theoretical and research attention are identified.

PMID- 11293369
TI  - The relational treatment of dissociative identity disorder.
AB  - The intent of this paper is to review the literature pertaining to the
      transference and countertransference components in the treatment of dissociative
      identity disorder. Aspects of transference and countertransference are presented
      and discussed within the relational psychoanalytic model. The functions of
      empathy, enactment, projective identification, and transitional objects are
      reviewed. Specific attitudes in the transference and countertransference are
      illuminated and major transference themes are discussed. Finally, a case vignette
      illustrates some of the central issues involved in the treatment of dissociative
      identity disorder.

PMID- 11293371
TI  - Article fails to recognize unequal partners equal odd coupling.

PMID- 11293370
TI  - Wasn't A.T. still an MD, too?

PMID- 11293372
TI  - On becoming a doctor.

PMID- 11293373
TI  - Predicting factors of successful recovery from lumbar spine surgery among
      workers' compensation patients.
AB  - It is commonly believed that patients who are compensated for a work-related
      injury have less incentive to return to work. This study evaluated how various
      factors affected the outcomes of lumbar spine surgery in terms of pain relief,
      functional status, return to work, and general health. Eighty-seven workers'
      compensation patients had spinal fusion or microdiskectomy. Subjects were
      evaluated preoperatively and postoperatively using the Oswestry disability scale
      and the Visual Analog Scale for Pain. The type of surgery performed significantly
      affected patient outcomes, while such factors as gender, age, smoking, and
      litigation were insignificant. Microdiskectomy patients, for example, had greater
      reduction in pain and disability than did fusion patients (P < .01). Return-to
      work status was negatively affected by fusion (P < .01). Overall, 55% of patients
      did return to work in some capacity, but the rate was 72% for microdiskectomy
      patients versus 43% for fusion patients. While outcomes significantly improved,
      postoperative scores remained severe. This did not correlate with return-to-work
      rates, suggesting that outcomes measures may not be effective.

PMID- 11293374
TI  - Prediction of student performance on the Comprehensive Osteopathic Medical
      Licensing Examination Level I based on admission data and course performance.
AB  - To predict student performance on the Comprehensive Osteopathic Medical Licensing
      Examination (COMLEX-USA) Level 1 examination based on academic performance during
      the first 2 years, stepwise regression analysis of COMLEX-USA Level 1 performance
      with preadmission grade point averages, Medical College Admission Test scores,
      and academic performance was performed on the class of 2000 to develop three
      formulae that were then used to predict performance on COMLEX-USA Level 1 for the
      class of 2001. Models ranged in accuracy of predicting the pass/fail status from
      95.2% (all available data) to 96.8% (first-year grades and admissions data). A
      predictive model for student performance on COMLEX-USA Level 1 can be developed
      and has a high degree of accuracy. The model with the most variables available to
      choose from predicts the most failures.

PMID- 11293375
TI  - Partial spectrum of microorganisms found in dentures and possible disease
      implications.
AB  - While it would appear that denture surfaces alone become colonized by
      microorganisms, this study showed that the porosity of denture material allows
      for contamination throughout the entire denture. Further, the numerous
      opportunistic and pathogenic microorganisms found in this study were unexpected
      and are known to produce not only substantial oral infections, but also systemic
      diseases.

PMID- 11293376
TI  - Research--beginning the modern era.

PMID- 11293377
TI  - Preconception care: "VITAL MOM"--a guide for the primary care provider.
AB  - Preconception care is an important aspect of pregnancy-related care.
      Unfortunately, it is often ignored or minimized by both the patient and the
      provider. This article provides a framework for preconception care by offering
      the mnemonic "VITAL MOM." It is hoped that this offering will assist the
      clinician in optimizing pregnancy outcome.

PMID- 11293378
TI  - Diabetes in pregnancy.
AB  - Diabetes mellitus is one of the most common medical complications of pregnancy.
      Two percent to 5% of pregnancies are complicated by diabetes, of which 90% are
      classified as gestational diabetes mellitus. Prevention of the fetal and maternal
      complications of diabetes presents unique challenges to all providers of
      healthcare to reproductive-aged diabetic women. The management of diabetes
      before, during, and after pregnancy can serve as a model of preventive
      healthcare. Preconception counseling and metabolic control before pregnancy
      reduce the rate of congenital malformations and the burden of suffering in
      offspring.

PMID- 11293379
TI  - Management of preterm labor.
AB  - Preterm labor and delivery continues to be one of the most serious problems in
      obstetrics, both medically and socioeconomically. The more classically used
      definitions of preterm delivery may not be useful in this era of advances in
      neonatal care. Similarly, the classically used criteria for "success" in
      tocolysis may obscure benefits from prolongation of gestation that does not meet
      these criteria. This article reviews the etiologic theories, risk factors,
      diagnostic techniques, and possible primary and adjunctive modes of therapy for
      preterm labor. The emphasis of these recommendations is on their clinical utility
      for the practicing obstetric care provider.

PMID- 11293380
TI  - Clinical review of home uterine activity monitoring (HUAM).
AB  - Preterm birth is associated with significant neonatal mortality and morbidity
      nationwide. Multiple strategies have been used to attempt to reduce the incidence
      of preterm births, and none have been entirely successful. The current review
      contains assessment of recent literature and home uterine activity monitoring. It
      also makes some suggestions about how and when this diagnostic modality may be
      used in current obstetric practice.

PMID- 11293381
TI  - [Russian Federation.  Federal Law.  On the mandatory social workman's
      compensation in workplace and in occupational diseases].

PMID- 11293382
TI  - Miles R. Markley.

PMID- 11293383
TI  - [Descriptive analysis of the Nefrologia 2000 survey].

PMID- 11293384
TI  - The pathogenesis of sexual mucosal transmission and early stages of infection:
      obstacles and a narrow window of opportunity for prevention.

PMID- 11293385
TI  - Up-date on microbicide clinical trials for the Microbicide 2000 Conference.

PMID- 11293386
TI  - Microbicides 2000 conference. Welcoming remarks. Expanding our prevention
      options: the role of the international community in providing an enabling
      environment for microbicides.

PMID- 11293387
TI  - Microbicides 2000 conference. Welcoming remarks. The role of the women's health
      movement in microbicide development.

PMID- 11293388
TI  - Resource allocation.

PMID- 11293389
TI  - The effects of exercise on the pharmacokinetics of drugs.
AB  - According to the limited information available, exercise has no substantial
      effect on the absorption of orally given drugs. However, it appears to enhance
      absorption from intramuscular, subcutaneous, transdermal and inhalation sites.
      The effects of exercise on drug distribution are complex. Exercise increases
      muscular blood flow resulting, for example, in the increased binding of digoxin
      in working skeletal muscle. On the other hand, exercise may sequester some drugs
      such as propranolol in muscle and reduce the availability of the drug for
      elimination. In addition, exercise decreases the clearance of highly extracted
      drugs and increases their plasma concentration. It may also increase the
      clearance of drugs by increasing biliary excretion. Since exercise reduces renal
      blood flow, the plasma concentrations of those drugs which are primarily
      eliminated by the kidneys may increase. In conclusion, if maintaining the plasma
      concentration of a drug at a certain level is important, consideration should be
      given to alternative drugs if the patient is on intermittent or irregular
      exercise.

PMID- 11293391
TI  - Abnormal lipoprotein and marked hypercholesterolemia as paraneoplastic
      manifestation of a renal adenocarcinoma.

PMID- 11293392
TI  - Statin-fibrate combinations in patients with combined hyperlipedemia.

PMID- 11293394
TI  - Bibliography. Current world literature. Transplantation.

PMID- 11293393
TI  - High-dose simvastin (80 mg/day) decreases plasma concentrations of total
      homocyst(e)ine in patients with hypercholesteromia.

PMID- 11293395
TI  - Bibliography. Current world literature. Lung and mediastinum.

PMID- 11293397
TI  - Bibliography. Current world literature. Obstructive, occupational, and
      environmental diseases.

PMID- 11293396
TI  - Bibliography. Current world literature. Melanoma and other skin neoplasms.

PMID- 11293398
TI  - Prognosis following a second whiplash injury (Inj 2000;31:249-51).

PMID- 11293399
TI  - Attempted nailgun suicide: fluid management in penetrating cardiac injury.

PMID- 11293400
TI  - Chronic traumatic anterior knee pain Price AJ et al.

PMID- 11293401
TI  - Re: complications of tibial shaft soccer fractures.

PMID- 11293402
TI  - Beta-fibrinogen gene -455G/A polymorphism and coronary heart disease incidence:
      the Atherosclerosis Risk in Communities (ARIC) Study.
AB  - PURPOSE: The -455G/A (HaeIII) polymorphism of the beta-fibrinogen gene influences
      levels of plasma fibrinogen. We determined whether it influences risk of coronary
      heart disease. METHODS: We conducted a case-cohort study nested within a
      prospective investigation, the Atherosclerosis Risk in Communities Study. We
      accumulated 398 incident coronary heart disease cases over a median of 5.3 years
      of follow-up and compared their -455G/A status with a random sample of the cohort
      (n = 498). RESULTS: Plasma fibrinogen was higher (p = 0.04) in AA homozygous
      participants (341 mg/dL) than in persons carrying the G allele: GA (290 mg/dL),
      GG (298 mg/dL). However, there was no significant association between -455G/A and
      incident CHD. CONCLUSIONS: Although a small effect cannot be excluded, -455G/A
      does not appear to be an important genetic determinant of CHD.

PMID- 11293403
TI  - The use of census data for determining race and education as SES indicators: a
      validation study.
AB  - PURPOSE: Little research has examined the validity of using census data to
      determine an individual's socio-economic status (SES), as measured by race and
      educational level. This study assessed the accuracy of using aggregate level data
      from United States Census Block Groups in determining race and education SES
      indicators in a cohort of women from North Carolina. METHODS: The study analyzed
      patient data from the Carolina Mammography Registry and 1990 United States Census
      in 21 North Carolina counties. Women (n = 39,546) were geocoded to their census
      block group and their block group characteristics (surrogate measures) were
      validated with their self-reported values on race and education. An analysis was
      performed to explore whether using these surrogate measures would affect measured
      associations with the self-reported values. RESULTS: Whites were accurately
      identified (84.8%) more consistently than Blacks (14.1%) regardless of their
      urban/rural status. Women without a high school diploma or equivalent were
      accurately identified (56.2%) more often than those with higher education levels
      (45.9%). Analyses using the surrogate measures were significantly different than
      the true values according to chi-square statistics. CONCLUSIONS: Use of census
      data to derive SES indicators tends to be more accurate for the majority than the
      minority population. Researchers must be sensitive to the ecologic fallacy when
      using aggregate level data such as the census to determine individual level
      characteristics.

PMID- 11293404
TI  - Metal ion binding and activation of Streptomyces griseus dinuclear
      aminopeptidase: cadmium(II) binding as a model.
AB  - A detailed metal binding and activation of the dinuclear aminopeptidase from
      Streptomyces griseus (sAP) has been analyzed and modeled by means of metal
      titration as well as kinetic and thermodynamic techniques using Cd2+ as a probe.
      Cd2+ binds to the two metal-binding sites in a sequential manner to produce a
      very active Cd2+-substituted derivative, particularly in the presence of Ca2+
      (53% and 90%, respectively, relative to the activities of the native form in
      terms of kcat/Km under the same conditions). The first stepwise formation
      constant for the binding of metal to the dinuclear site (to form M-sAP) was found
      to determine the metal-binding selectivity, regardless of the magnitude of the
      second stepwise formation constant (to form M,M-sAP from M-sAP). Interestingly,
      despite the seemingly very different binding profiles for different metal ions
      under different conditions, all of them can be well described and fitted by the
      sequential binding model. In addition, Ca2+ was found to significantly affect
      metal binding, inhibition, and entropy of activation of this enzyme, and its role
      in sAP action is re-evaluated.

PMID- 11293405
TI  - In vitro study of the insulin-like action of vanadyl-pyrone and -pyridinone
      complexes with a VO(O4) coordination mode.
AB  - The insulin-like action of a novel class of potential insulin-mimetic complexes
      was investigated in terms of free fatty acid (FFA) release from isolated rat
      adipocytes. Vanadyl complexes such as VO(ema)2 [(bis(2-ethyl-3-hydroxy-4
      pyrone)VO], VO(mpp)2 [bis (3-hydroxy-2-methyl-4(1H)-pyridinone)VO], VO(dmpp)2
      [bis(1,2-dimethyl-3-hydroxy-4(1H)-pyridinone)VO] and VO(empp)2 [bis(2-ethyl-3
      hydroxy-1-methyl-4(1H)-pyridinone)VO] were tested together with vanadyl sulfate
      for comparison. The inhibitory effect of the vanadium complexes on FFA release,
      from rat adipocytes treated with epinephrine, is dependent on concentration and
      for that reason the results are reported in terms of the IC50 value, the 50%
      inhibition concentration. The results show that all the complexes have an
      inhibitory effect on FFA release and that two pyridinone complexes, VO(mpp)2 and
      VO(empp)2, have a significantly better insulin-mimetic activity than that of
      vanadyl sulfate.

PMID- 11293406
TI  - A new halogenated antidiabetic vanadyl complex, bis(5
      iodopicolinato)oxovanadium(IV): in vitro and in vivo insulinomimetic evaluations
      and metallokinetic analysis.
AB  - A new vanadyl complex, bis(5-iodopicolinato)oxovanadium(IV), VO(IPA)2, with a
      VO(N2O2) coordination mode, was prepared by mixing 5-iodopicolinic acid and VOSO4
      at pH 5, with the structure characterized by electronic absorption, IR, and EPR
      spectra. Introduction of the halogen atom on to the ligand enhanced the in vitro
      insulinomimetic activity (IC50 = 0.45 mM) compared with that of
      bis(picolinato)oxovanadium(IV) (IC50 = 0.59 mM). The hyperglycemia of
      streptozotocin-induced insulin-dependent diabetic rats was normalized when
      VO(IPA)2 was given by daily intraperitoneal injection. The normoglycemic effect
      continued for more than 14 days after the end of treatment. To understand the
      insulinomimetic action of VO(IPA)2, the organ distribution of vanadium and the
      blood disposition of vanadyl species were investigated. In diabetic rats treated
      with VO(IPA)2, vanadium was distributed in almost all tissues examined,
      especially in bone, indicating that the action of vanadium is not peripheral.
      Vanadyl concentrations in the blood of normal rats given VO(IPA)2 remain
      significantly higher and longer than those given other complexes because of its
      slower clearance rate. VO(IPA)2 binds with the membrane of erythrocytes, probably
      owing to its high hydrophobicity in addition to its binding with serum albumin.
      The longer residence of vanadyl species shows the higher normoglyceric effects of
      VO(IPA)2 among three complexes with the VO(N2O2) coordination mode. On the basis
      of these results, VO(IPA)2 is indicated to be a preferred agent to treat insulin
      dependent diabetes mellitus in experimental animals.

PMID- 11293407
TI  - The design of new molecular "light switches" for DNA.
AB  - Two novel ruthenium(II) complexes, [Ru(pztp)2(phen)](ClO4)2 and [Ru(pztp)2(bpy)]
      (ClO4)2, have been synthesized and characterized by UV/Vis and 1H NMR
      spectroscopies and mass spectrometry. The MeCN solutions of both complexes
      display fluorescence that was found to be highly sensitive to the presence and
      concentration of water. The complexes behave like a "light switch" for DNA in
      that they do not luminesce in water but were "turned on" in the presence of DNA
      and show emission enhancement with the increase of DNA concentration. Their DNA
      binding behavior was also studied by absorption spectroscopy and viscosity
      measurements, which suggest that the DNA-complex interaction involves
      intercalation of the metal-bound pztp ligand into the base pairs of duplex DNA.

PMID- 11293408
TI  - Formation of a protonated trihydrobiopterin radical cation in the first reaction
      cycle of neuronal and endothelial nitric oxide synthase detected by electron
      paramagnetic resonance spectroscopy.
AB  - Nitric oxide synthase (EC 1.14.13.39; NOS) converts L-arginine into NO and L
      citrulline in a two-step reaction with Nomega-hydroxy-L-arginine (NOHLA) as an
      intermediate. The active site iron in NOS has thiolate axial heme-iron ligation
      as found in the related monooxygenase cytochrome P450. In NOS,
      tetrahydrobiopterin (BH4) is an essential cofactor for both steps, but its
      function is controversial. Previous optical studies of the reaction between
      reduced NOS with O2 at -30 degrees C suggested that BH4 may serve as an one
      electron donor in the first cycle, implying formation of a trihydrobiopterin
      radical. We investigated the same reaction under identical conditions with
      electron paramagnetic resonance spectroscopy. With BH4-containing full-length
      neuronal NOS we obtained an organic free radical (g-value 2.0042) in the presence
      of Arg, and a similar radical was observed with the endothelial NOS oxygenase
      domain in the presence of Arg and BH4. Without substrate the radical yield was
      greatly (10x) diminished. Without BH4, or with NOHLA instead of Arg, no radical
      was observed. With 6-methyltetrahydropterin or 5-methyl-BH4 instead of BH4,
      radicals with somewhat different spectra were formed. On the basis of simulations
      we assign the signals to trihydropterin radical cations protonated at N5. This is
      the first study that demonstrates the formation of a protonated trihydrobiopterin
      radical with the constitutive isoforms of NOS, and the first time the radical was
      obtained without exogenous BH4. These results offer strong support for redox
      cycling of BH4 in the first reaction cycle of NOS catalysis (BH4 <--> BH3.H+).

PMID- 11293410
TI  - Targeted site-specific cleavage of HIV-1 viral Rev responsive element by copper
      aminoglycosides.
AB  - Site-specific cleavage of the HIV-1 viral Rev responsive element by copper
      aminoglycosides is reported under physiological conditions. This bubble and stem
      loop RNA structure is efficiently targeted at micromolar concentrations of
      complex. The specificity of cleavage of structured viral RNA relative to a non
      cognate tRNAPhe of well-defined secondary and tertiary structure is demonstrated.
      Cleavage products from simpler substrates [diribonucleotide (ApA) and 2',3'
      cyclic monophosphate ester (cAMP)] were analyzed by 31P NMR and demonstrate a
      hydrolytic mechanism in the absence of external redox agents. These results
      demonstrate copper aminoglycosides to be highly efficient chemical nucleases with
      a targeting capability for viral RNA and suggest a novel methodology to counter
      RNA viruses.

PMID- 11293409
TI  - Novel lipophilic amidate oxorhenium and oxotechnetium complexes as potential
      brain agents: synthesis, characterization and biological evaluation.
AB  - Novel oxorhenium and oxotechnetium complexes based on the tetradentate 1-(2
      hydroxybenzamido)-2-(pyridinecarboxamido)benzene, H3L, ligand have been
      synthesized and characterized herein. Thus, by reacting equimolar quantities of
      the triply deprotonated ligand L3- with the suitable MO3+ precursor, the
      following neutral MOL complexes could be easily produced following similar
      synthetic routes: M = Re (1), M = 99gTc (2), and M = 99mTc (3). Complexes 1 and
      2, prepared in macroscopic amounts, were chemically characterized and their
      structure determined by single-crystal X-ray analysis. They are isostructural
      metal chelates, adopting a distorted square pyramidal geometry around the metal.
      The N3O donor atom set of the tetradentate ligand defines the basal plane and the
      oxygen atom of the M = O core occupies the apex of the pyramid. Complex 3 forms
      quantitatively at tracer level by mixing the H3L ligand with Na99mTcO4 generator
      eluate in aqueous alkaline media and using tin chloride as reductant in the
      presence of citrate. Its structure was established by chromatographic comparison
      with prototypic complexes 1 and 2 using high-performance liquid chromatographic
      techniques. When challenged with excess glutathione in vitro, complex 3 is
      rapidly converted to hydrophilic unidentified metal species. Tissue distribution
      data after administration of complex 3 in vivo revealed a significant uptake and
      retention of this compound in brain tissue.

PMID- 11293411
TI  - Chimeric HTH motifs based on EF-hands.
AB  - The design of a new peptide construct from two structurally equivalent basis
      motifs is reported. A chimera was designed from the helical regions of a helix
      turn-helix (HTH) domain, incorporating the consensus EF-hand Ca-binding loop at
      the turn. Two 33-residue peptides were constructed: one (P3, designed) includes
      the 12-residue consensus EF-hand loop, while the other (P2, control) contains the
      reversed EF-hand loop sequence. The Eu(III) and Ca(II) binding properties of P2
      and P3 were investigated by circular dichroism and NMR. The designed peptide (P3)
      is 25% helical in its Eu(III)-saturated form, and 14% helical with excess Ca(II).
      Both the free and Eu-bound peptides have inherent solution structure, as
      demonstrated by the helicity induced by the addition of trifluoroethanol solvent.
      While Eu(III) binding stabilizes the structure of P3, it destabilizes the
      structure of P2. The NMR titration of P3 with Eu(III) resulted in new resonances
      characteristic of Ca-bound EF-hand loops. As observed for isolated EF-hands, the
      resonances appear within the first 0.5 equivalents of Eu(III) added, suggesting
      that one metal ion organizes two equivalents of peptide to fold into the back-to
      back dimer structure of native EF-hands. The EuP3 chimera, but not EuP2, has
      significant affinity for supercoiled plasmid DNA, causing a gel shift at
      concentrations as low as 10 microM EuP3 (50 microM base pairs). These results
      show our chimeric peptide combines the characteristics of the parent motifs,
      maintaining both metal binding and DNA affinity.

PMID- 11293412
TI  - Probing copper ligands in denatured Pseudomonas aeruginosa azurin: unfolding
      His117Gly and His46Gly mutants.
AB  - Azurin is a single-domain beta-barrel protein with a redox-active copper
      cofactor. Upon Pseudomonas aeruginosa azurin unfolding, the cofactor remains
      bound to the polypeptide, coordinating three ligands: cysteine-112, one histidine
      imidazole, and a third, unknown ligand. In order to identify which histidine
      (histidine-117 and histidine-46 both coordinate copper in native azurin) is
      involved in copper coordination in denatured azurin, two single-site (histidine
      to glycine) mutants, His117Gly and His46Gly azurin, are investigated here.
      Equilibrium denaturation experiments of His46Gly azurin loaded with copper
      demonstrate that copper remains bound to this mutant in high urea concentrations
      where the protein's secondary structure is lost. In contrast, for copper-loaded
      His117Gly azurin, copper does not stay coordinated upon polypeptide unfolding.
      The copper absorption at 370 nm in denatured His46Gly azurin agrees with that for
      copper in complex with a peptide corresponding to residues 111-123 in azurin,
      suggesting similar metal coordination. We conclude that histidine-117 (and not
      histidine-46) is the histidine copper ligand in denatured azurin. This is also in
      accord with the proximity of histidine-117 to cysteine-112 in the primary
      sequence.

PMID- 11293413
TI  - Expression, purification, and characterization of NosL, a novel Cu(I) protein of
      the nitrous oxide reductase (nos) gene cluster.
AB  - NosL, one of the accessory proteins of the nos (nitrous oxide reductase) gene
      cluster, has been heterologously expressed, purified, and characterized. NosL is
      a monomeric protein of 18,540 MW that specifically and stoichiometrically binds
      Cu(I). The copper ion in NosL is ligated by a Cys residue, and one Met and one
      His are thought to serve as the other ligands. While it is possible to oxidize
      Cu(I)-NosL with ferricyanide, the Cu(II) ion thus formed appears to dissociate
      from the protein. The function of Cu(I)NosL is not yet known, but the data
      indicate that NosL does not act as an electron transfer partner to nitrous oxide
      reductase. NosL is encoded on the same transcript as three other gene products
      (NosD, NosF, and NosY). These have been shown to be required for assembly of the
      active site in nitrous oxide reductase, which is thought to be a copper cluster.
      Accordingly, it is possible that NosL is a copper chaperone involved in
      metallocenter assembly.

PMID- 11293414
TI  - Stereospecific binding of MRI contrast agents to human serum albumin: the case of
      Gd-(S)-EOB-DTPA (Eovist) and its (R) isomer.
AB  - The water proton relaxation rate enhancement of the hepatospecific Gd-(S)-EOB
      DTPA (Eovist) and of its (R) isomer in aqueous solutions free of protein, in
      serum and in 4% human serum albumin solution, are compared. In the absence of
      proteins, both compounds exhibit, as expected, the same proton relaxivity, as
      measured by the nuclear magnetic relaxation dispersion (NMRD) profiles. In serum
      and albumin solution, non-covalent binding of the paramagnetic complexes to
      macromolecules is observed. Both isomers are likely to bind to the same site of
      human serum albumin, but the affinity of the (S) isomer is larger than for the
      (R) isomer.

PMID- 11293415
TI  - Analysis of metal incorporation during overexpression of Clostridium pasteurianum
      rubredoxin by electrospray FTICR mass spectrometry.
AB  - The rate of production of Clostridium pasteurianum rubredoxin overexpressed in
      Escherichia coli was examined by electrospray ionization-Fourier transform ion
      cyclotron resonance (ESI-FTICR) mass spectrometry. Previous work had shown that
      this heterologous expression resulted in isolation of both iron-containing (FeRd)
      and zinc-containing (ZnRd) rubredoxins. In the present work, minimally processed
      cell lysates of E. coli were analyzed in order to monitor the production of FeRd
      and ZnRd. The sensitivity of the measurement favored FeRd relative to ZnRd, and
      this differential sensitivity was quantitated using previously separated and
      purified rubredoxins. A time course study indicated that ZnRd and FeRd are
      produced simultaneously during overexpression, but at different rates. The ratio
      of the concentration of ZnRd to FeRd increased in a linear fashion during 3 h
      following induction of overexpression. Since only FeRds have been reported from
      native bacteria and archaea, the data suggest that either Zn2+ is sequestered
      from rubredoxins during native biosynthesis or that ZnRds may have escaped
      detection in the native microorganisms. ESI-FTICR mass spectrometry is shown to
      be a useful tool for monitoring metal insertion during protein biosynthesis.

PMID- 11293416
TI  - Limits to demand for health care. Article contained several fallacies.

PMID- 11293417
TI  - Limits to demand for health care. Rationing is needed in a national health
      service.

PMID- 11293418
TI  - Limits to demand for health care. Gap between demand for services and cost of
      providing them should certainly be assessed.

PMID- 11293419
TI  - NHS needs plan for all acute, rehabilitative, and long stay care.

PMID- 11293420
TI  - Driving after hernia surgery. Patients should be advised not to drive for 10
      days.

PMID- 11293421
TI  - Driving after hernia surgery. Claims in editorial from Lichtenstein Hernia
      Institute are unsubstantiated.

PMID- 11293422
TI  - Research in complementary medicine is essential.

PMID- 11293423
TI  - Continuity in general practice. Continuity is fine, but not for everything.

PMID- 11293424
TI  - Continuity in general practice. Continuity of care is not all or nothing.

PMID- 11293425
TI  - Hamster health care can be solved with more funding.

PMID- 11293432
TI  - Blood pressure in diabetic nephropathy--current controversies.
AB  - Hypertension has been recognized as an early and constant feature of diabetic
      nephropathy, but recent studies also suggest that a genetic predisposition to
      hypertension is an important risk factor for diabetic nephropathy.
      Antihypertensive treatment attenuates progression in diabetic nephropathy, but
      there is increasing evidence that very early treatment and very low target blood
      pressures should be implemented. There is also evidence for local activation of
      the renin system in the kidney as a result of hyperglycaemia. Apart from blood
      pressure, proteinuria should be monitored and dosing of ACE inhibitors should be
      guided, also by reduction of protein excretion.

PMID- 11293433
TI  - In regard to Joon et al. IJROBP 1999;45:1199-1205.

PMID- 11293434
TI  - Weekend warriors.

PMID- 11293435
TI  - Reduction of target dose inhomogeneity in IMRT treatment planning using biologic
      objective functions.

PMID- 11293436
TI  - A new power law for determination of total I-125 seed activity for ultrasound
      guided prostate implants: clinical evaluations. In regard to Wu et al. IJROP
      2000;47:1397-1403.

PMID- 11293437
TI  - In regard to Fowble et al. IJROBP 2000;47:883-894.

PMID- 11293438
TI  - Hypofractionation for prostate cancer.

PMID- 11293439
TI  - Irritable bowel syndrome: is the search for lactose intolerance justified?
AB  - OBJECTIVES: To determine if confirmation of hypolactasia offers any benefit to
      the dietary treatment of patients with irritable bowel syndrome (IBS). METHODS:
      One hundred and twenty-two consecutive IBS patients (37 male, 85 female) were
      given lactose hydrogen breath tests (LHBT). Those with positive LHBT followed a
      low lactose diet for 3 weeks. Those improving on the diet were given double
      blind, placebo-controlled challenges (DBPCC) with 5 g, 10 g and 15 g of lactose
      and a placebo, to confirm lactose intolerance. Those who did not respond to the
      low lactose diet followed either an exclusion or low fibre diet. Symptoms scores
      were kept prior to the LHBT, 8 h post-LHBT and daily whilst following any dietary
      change. Patients with negative LHBT returned to clinic and subsequent dietary
      interventions were recorded. RESULTS: LHBT was positive in 33/122 (27%) IBS
      patients. Syrr otom scores prior to LHBT were not significantly different between
      the two groups, but after LHBT the symptoms in the positive group were
      significantly worse. Twenty-three patients followed a low-lactose diet of which
      only nine (39%) improved. Six who did not improve followed an exclusion diet,
      three improved and all were intolerant of milk. Three tried a low fibre diet with
      two improving. DBPCC were inconclusive. In the negative LHBT group 35 agreed to
      try a diet and 24 improved (69%). Eight were intolerant of cow's milk.
      CONCLUSIONS: Use of a low lactose diet was disappointing in IBS patients with
      lactose malabsorption. Food intolerance was demonstrated in IBS patients with
      positive or negative LHBT and milk was identified as a problem in both groups.
      DBPCC were inconclusive. There appears to be little advantage in trying to
      separate patients who malabsorb lactose from others with IBS.

PMID- 11293440
TI  - Serum anti-Lewis X antibody is associated with VacA seropositivity but not
      atrophic gastritis in patients with Helicobacter pylori infection.
AB  - OBJECTIVES: Lipopolysaccharides of Helicobacter pylori have an antigenic
      structure that mimics Lewis X occurring in gastric mucosa. The pathogenic role of
      antigenic mimicry in H. pylori-induced gastritis has been of recent interest. The
      aim of this study was to examine the relevance of anti-Lewis X antibody in the
      development of atrophic gastritis in H. pylori infection. METHODS: A total of 72
      patients were studied. Serum samples were collected to measure IgG antibodies to
      H. pylori, CagA, VacA and Lewis X. Biopsy specimens were obtained from the antrum
      and the corpus to examine the grade and the type of atrophic gastritis. RESULTS:
      Mean anti-Lewis X antibody titres were higher in 38 VacA-seropositive patients
      than in 13 seronegative patients (P < 0.05). The difference was not significant
      between patients with diffuse-type atrophic gastritis and those with multi-focal
      type. No significant correlation was observed between the titre of anti-Lewis X
      antibody and the grade of glandular atrophy, whereas CagA seropositivity was
      associated with glandular atrophy. CONCLUSIONS: Anti-Lewis X antibody may play a
      role in persistent gastric inflammation, particularly in VacA-seropositive H.
      pylori infection. However, anti-Lewis X antibody does not seem itself to be
      associated with atrophic gastritis in patients with H. pylori infection.

PMID- 11293441
TI  - Helicobacter pylori infection reduces systemic availability of dietary vitamin C.
AB  - OBJECTIVE: Helicobacter pylori infection is recognized to lower the concentration
      of vitamin C in gastric juice. The objective of this study was to assess the
      effect of the infection on the systemic availability of dietary vitamin C.
      METHODS: The study involved 1,106 men and women aged 25-74 randomly recruited
      from the population of north Glasgow. Their H. pylori status, dietary vitamin C
      intake calculated from a food frequency questionnaire and plasma vitamin C
      concentration were measured. Correction was made for potential confounding
      factors such as age, sex, smoking and social status. RESULTS: The mean plasma
      vitamin C concentration in those who were H. pylori-positive was only 65% of that
      in those classified negative. Although partly explained by differences in age,
      sex, social class, smoking and vitamin C intake, the systemic reduction was
      observed across almost all sub-groups after stratification. Correction for all
      these factors still gave a plasma vitamin C level for H. pylori positives which
      was only 80% of that for negatives (P < 0.0001). CONCLUSIONS: H. pylori
      substantially impairs the bio-availability of vitamin C. This, together with the
      reduced vitamin C intake of H. pylori-positive subjects, markedly reduces the
      plasma vitamin C level of infected subjects. The reduced circulating levels of
      vitamin C in H. pylori-infected subjects may contribute to the aetiology of
      gastric cancer, as well as other diseases associated with anti-oxidant
      deficiency.

PMID- 11293442
TI  - Gut luminal neutrophil migration is influenced by the anatomical site of Crohn's
      disease.
AB  - BACKGROUND: Clinical differences between small- and large-bowel Crohn's disease
      have been demonstrated. Neutrophil migration and degranulation are important
      effector mechanisms in gut damage. Granulocyte elastase, a neutrophil-bound
      enzyme, interleukin 8 and 1beta can be detected in whole-gut lavage fluid. We
      aimed to assess differences between large- and small-bowel Crohn's disease.
      METHODS: A total of 167 patients with active inflammatory bowel disease (118
      Crohn's disease, 49 ulcerative colitis) underwent whole-gut lavage with a
      polyethylene glycol electrolyte solution. Granulocyte elastase was assayed using
      an enzyme substrate reaction, IL-8 and IL-1beta by ELISA. RESULTS: Twenty-seven
      of 36 patients with isolated colonic Crohn's disease had detectable granulocyte
      elastase (median 0.259 pKat/l, range < 0.039-2.742 microKat/l), whereas 3 of 15
      with small-bowel involvement alone had detectable granulocyte elastase (median <
      0.039 microKat/l, range < 0.039-0.266 microKat/l; P < 0.0001). Granulocyte
      elastase levels were significantly higher in patients with ileocolonic disease
      and post-ileocaecal resection compared with small-bowel disease alone. IL-8 (P<
      0.0001) and IL-1beta (P < 0.04) levels differed between colonic and ileal
      distributions. No variations were seen in ulcerative colitis. CONCLUSIONS:
      Neutrophil migration to the gut lumen in Crohn's disease is a feature of colonic
      disease irrespective of associated ileal lesions. This suggests that bacterial
      derived chemo-attractants may play a role. High levels of IL-8 in colonic disease
      are consistent with this hypothesis.

PMID- 11293443
TI  - Evolutive pattern in Crohn's disease: a simplified index using clinical
      parameters predicts obstructive behaviour.
AB  - BACKGROUND: Two clearly differentiated evolutive patterns of Crohn's disease,
      obstructive and fistulizing, exist, but the early clinical parameters which can
      predict the evolution are unknown. AIM: To evaluate whether clinical variables,
      present at the time of diagnosis, may help in predicting a subsequent evolutive
      behaviour. PATIENTS AND METHODS: Ninety out of 140 evaluable patients were
      included. After a median of 50.2 months since diagnosis, 64 patients (71%)
      followed an obstructive pattern while 26 patients (28.9%) had a fistulizing form.
      Clinical variables were analysed as predictors of outcome. Logistic regression
      was carried out in order to obtain a mathematical model that would predict the
      evolution. The individual ability of the mathematical model to predict evolution
      was assessed using relative receiver operating characteristic (ROC) curves.
      RESULTS: The variables which were retained in the model were duration of disease
      before diagnosis (DD), onset of symptoms (OS), presence of anal disease (AD) and
      the presence of abdominal mass (AM). The equation z = -9.49 + 2.2643 (AD) -
      0.0066 (DD) + 2.5282 (AM) + 1.3433 (OS) was obtained. The probability of
      evolution towards an obstructive form was P = 1/(1 + e(-Z)). This model can
      predict 96.88% of obstructive forms but only 53.85% of fistulizing forms. The
      mathematical point section (ROC curve) corresponds to a probability of 45.2%.
      Considering an obstructive pattern when the probabilities are above this point,
      the sensitivity is 98% and the specificity is 50%. CONCLUSIONS: The prediction of
      an obstructive pattern is feasible using simple clinical variables. The
      mathematical model obtained is useful for predicting this but not the fistulizing
      pattern.

PMID- 11293444
TI  - Relationships between haemodynamic alterations and the development of ascites or
      refractory ascites in patients with cirrhosis.
AB  - OBJECTIVE: In patients with cirrhosis, the relationships between haemodynamic
      alterations and the development of ascites or the occurrence of refractory
      ascites are unknown. The aim of the present study was to compare haemodynamic
      measurements obtained in patients with non-refractory ascites to haemodynamic
      measurements obtained in patients without ascites and in patients with refractory
      ascites. METHODS: A cohort of 121 patients was prospectively studied, of whom 29
      patients did not have ascites, 45 had non-refractory ascites and 47 had
      refractory ascites. Splanchnic, renal and systemic haemodynamics were measured in
      all patients. RESULTS: The hepatic venous pressure gradient was significantly
      higher in patients with non-refractory ascites than in patients without ascites
      (18.5 +/- 0.8 mmHg versus 15.8 +/- 0.7 mmHg). Renal and systemic haemodynamics
      did not significantly differ between patients with non-refractory ascites and
      patients without ascites. The glomerular filtration rate and renal blood flow
      were significantly lower in patients with refractory ascites than in patients
      with non-refractory ascites (77 +/- 4 versus 107 +/- 5 ml/min and 867 +/- 62
      versus 1,008 +/- 68 ml/min, respectively). Splanchnic and systemic haemodynamics
      did not significantly differ between patients with refractory ascites and
      patients with non-refractory ascites. CONCLUSIONS: In patients with cirrhosis, an
      increase in portal hypertension was the sole haemodynamic alteration related to
      the development of ascites. Renal vasoconstriction (and subsequent renal
      hypoperfusion and hypofiltration) was the only haemodynamic alteration related to
      the occurrence of refractory ascites. The development of ascites or refractory
      ascites was not associated with any alteration in systemic haemodynamics.

PMID- 11293445
TI  - Transjugular intrahepatic portosystemic stent-shunt insufficiency and the role of
      diabetes mellitus.
AB  - BACKGROUND/AIMS: Maintenance of long-term patency of transjugular intrahepatic
      portosystemic stent-shunts (TIPSS) has proved problematic. Various prognostic
      variables have been assessed as predictors, but the role of diabetes mellitus,
      which induces vascular endothelial cell dysfunction, has not been assessed.
      METHODS: We analysed the records of 248 patients who underwent TIPSS between July
      1991 and July 1997, followed-up through to August 1998. Patients with at least
      one shunt assessment by portography and available blood glucose levels were
      eligible (177 patients; median follow-up, 15.0 months). Fourteen patients had a
      pre-procedural diagnosis of diabetes (one insulin dependent, seven oral
      hypoglycaemic treated and six diet controlled). In another 14 patients, diabetes
      was diagnosed at TIPSS insertion, giving a 28/177 (15.8%) prevalence of diabetes
      in our patients. Fifty-nine patients were excluded from the final analysis
      (including five diabetics), as they either died or had early shunt insufficiency
      (within 1 month of stent placement), leaving 118 patients (including 23
      diabetics) to be included in the final analysis. RESULTS: Mean age, sex
      distribution, median follow-up (months) and pre-shunt portal pressure gradient
      were comparable in the two groups (diabetics versus non-diabetics). Child-Pugh
      classes A and B were more common in the diabetic group (P < 0.01), and the mean
      inserted stent diameter was larger in the diabetic group (P < 0.05). The presence
      of diabetes was associated with a higher incidence of delayed shunt insufficiency
      (P = 0.02), but there was no evidence of an association between presence of
      diabetes and variceal haemorrhage post TIPSS. Kaplan-Meier analyses revealed
      earlier insufficiency in diabetic patients compared with those without diabetes
      (P = 0.04). Age, gender and presence of diabetes are included in the final
      logistic regression model. Individuals who have diabetes are more likely to
      experience shunt insufficiency independent of age and gender. CONCLUSIONS:
      Diabetes mellitus is common in patients undergoing TIPSS and is associated
      independently with increased incidence of primary delayed shunt insufficiency.

PMID- 11293446
TI  - Prevalence of coeliac disease in Down's syndrome.
AB  - OBJECTIVE: During the past decade, it has been shown that the association between
      Down's syndrome and coeliac disease is relatively frequent Prevalence rates of
      coeliac disease in patients with Down's syndrome reported by different authors
      are significantly higher than those found in the general population. The main
      purpose of this study was to assess the prevalence of coeliac disease in a series
      of subjects with Down's syndrome from our geographical area. DESIGN: A cross
      sectional study. SETTING: Outpatient paediatric clinics of acute-care teaching
      hospitals in Barcelona, Spain. PARTICIPANTS: A total of 284 persons with Down's
      syndrome aged between 1 and 25 years were included in the study. In all cases,
      serum concentrations of antigliadin antibodies (AGAs) (Pharmacia CAP system
      enzyme-linked immunosorbent assay), antiendomysium antibodies (AEA) (indirect
      immunofluorescence) of immunoglobulin (Ig)A class or IgG class in cases of IgA
      deficiency were determined. Jejunal biopsy was offered to all patients with AEA
      positivity and to those with suggestive clinical manifestations of coeliac
      disease. In all patients, a clinical study was made to evaluate the presence and
      time-course of symptoms related to coeliac disease. MAIN OUTCOME MEASURES AND
      RESULTS: In 18 of the 284 subjects with Down's syndrome, aged between 2 and 15
      years, coeliac disease was confirmed by jejunal biopsy. Accordingly, the minimum
      prevalence rate of coeliac disease was of 6.3%. Ninety-four percent (17/18) and
      78% (14/18) of patients with the association Down's syndrome and coeliac disease
      showed AEA and AGA positivity, respectively. Fifteen patients with the
      association coeliac disease and Down's syndrome (15/18) showed clinical
      manifestations compatible with coeliac disease, with a predominance of intestinal
      symptoms (8/18) over those with atypical or extra-intestinal forms (7/18). Three
      patients had clinically silent forms of coeliac disease (3/ 18). CONCLUSIONS:
      Measurement of serum concentrations of AEA should be added to the list of
      screening tests for coeliac disease in patients with Down's syndrome, otherwise
      definite association between both diseases may pass unnoticed and diagnosis of
      coeliac disease be considerably delayed.

PMID- 11293447
TI  - Time-course and clinical value of the urine trypsinogen-2 dipstick test in acute
      pancreatitis.
AB  - OBJECTIVE: Urine trypsinogen-2 has been suggested as a marker of damage due to
      acute pancreatitis. Our aim was to assess the time-course and the clinical value
      of this test in acute pancreatitis. METHODS: A urine trypsinogen-2 dipstick test
      was performed on 30 patients with acute pancreatitis upon admission to the
      emergency room, as well as on 30 patients with non-pancreatic acute abdominal
      pain, and in 30 healthy subjects. RESULTS: In 53.3% of the patients with acute
      pancreatitis the dipstick test showed abnormal urine trypsinogen-2 whereas this
      test gave negative results in all patients with non-pancreatic acute abdomen and
      in all healthy subjects. Patients with severe acute pancreatitis had a frequency
      of abnormal results of urine trypsinogen-2 (8/9, 88.9%; 95% CI, 51.8-99.7%)
      significantly higher (P = 0.031) than those with the mild disease (8/21, 38.1%;
      95% CI, 18.1 -61.6%), while no significant differences were found in the urine
      trypsinogen-2 results between patients with biliary acute pancreatitis and those
      with non-biliary acute pancreatitis. Regarding the time-course of urine
      trypsinogen-2, there were no significant differences during the three days of the
      study. CONCLUSIONS: The specificity of urine trypsinogen-2 in the diagnosis of
      acute pancreatitis is good however its sensitivity is low.

PMID- 11293448
TI  - Inferior vena cava obstruction in Budd-Chiari syndrome: successful treatment by
      radiological stenting followed by a portosystemic shunt.
AB  - Surgical decompression by a portosystemic shunt in Budd-Chiari syndrome depends
      on the caval state. Obstruction of the inferior vena cava (IVC) precludes such an
      operation due to the risk of reduced blood flow across the shunt and subsequent
      thrombosis. Similar risks are encountered in more complicated operations such as
      mesoatrial shunt. We report a patient with Budd-Chiari syndrome in whom
      obstruction of the intrahepatic IVC by a hypertrophied caudate lobe of the liver
      precluded the construction of a standard portocaval shunt. A two-step procedure
      with preoperative radiological stenting of the narrowed IVC followed by a
      portocaval shunt was successfully performed. This is the fifth case reported in
      the literature of such an approach.

PMID- 11293449
TI  - Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case
      report.
AB  - We report a case of fosinopril-induced prolonged cholestatic jaundice and
      pruritus in a 61-year-old man, with no previous hepatobiliary disease, who
      presented with asthenia, jaundice and itching 3 weeks after starting fosinopril
      therapy. Other drugs taken by the patient were not considered probable causes.
      The diagnostic evaluation showed no biliary obstruction and other possible causes
      of intra-hepatic cholestasis were excluded. Liver biopsy showed cholestasis
      without bile duct damage. The disease ran a severe course during the 2 months of
      hospitalization, with prolonged itching for 6 months, eventually controlled with
      oral naltrexone. Jaundice subsided after 4 months, with anicteric cholestasis
      persisting for more than 18 months. Similar occurrences have been reported with
      other inhibitors of angiotensin-converting enzyme (mostly captopril), but this is
      the first case of an important adverse reaction to fosinopril.

PMID- 11293450
TI  - Gastrointestinal stromal tumour of the rectum.
AB  - Gastrointestinal stromal tumour (GIST) has been immunohistochemically defined as
      the tumour lacking differentiation towards either leiomyomatous tumour or
      schwannoma. We report a 75-year-old man who underwent an abdominoperineal
      resection of a large submucosal tumour of the rectum. The excised specimen was
      revealed to be an elastic soft tumour, 8 x 7 x 6 cm in size, which histologically
      consisted of spindle-shaped cells without nuclear atypia. The mitotic count was
      fewer than 2 per 10 high-power fields. The tumour cells were positive for
      staining of CD34 and c-kit protein, while the lesions were negative for alpha
      smooth muscle actin, HHF-35, neuron-specific enolase, and S-100 protein. The
      diagnosis of GIST was confirmed by immunohistochemical examination of the tumour.
      From these findings, the present case is thought to be potentially malignant, and
      a long-term follow-up observation is needed for the case.

PMID- 11293451
TI  - Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular
      carcinoma after azathioprine treatment in a patient with ulcerative colitis.
AB  - We report the case of a 66-year-old male with ulcerative colitis diagnosed in
      1987, who had been treated with azathioprine (AZA) for the past two years
      (average dose about 1.6 mg/kg/day). In May 1999 he presented with painless
      jaundice, fatigue and recent weight loss. Cholestatic enzymes were elevated,
      alpha-fetoprotein was normal and hepatitis B/C serology negative. After diagnosis
      of veno-occlusive disease (VOD) and hepatocellular carcinoma (HCC) via biopsy,
      tumour resection was performed. The histology was typical for a well
      differentiated HCC with trabecular and pseudoglandular structures. Neighbouring
      liver tissue was atrophic, with nodular regenerative hyperplasia (NRH), peliosis
      like sinusoidal ectasias and intra-sinusoidal accumulation of blood, associated
      with peri-sinusoidal fibrosis. Although none of the well-established risk factors
      for HCC such as cirrhosis, hepatitis B/C, metabolic liver disease or toxins were
      present, this patient developed HCC. This and previous reports suggest that NRH
      and/or VOD associated with AZA represent a risk factor for HCC. AZA should
      therefore not only be stopped in patients with NRH/VOD but patients should also
      be screened for HCC.

PMID- 11293452
TI  - Rapid progression of hepatocellular carcinoma after transcatheter arterial
      chemoembolization and percutaneous radiofrequency ablation in the primary tumour
      region.
AB  - We report one patient who showed rapid progression of hepatocellular carcinoma
      (HCC) after undergoing transcatheter arterial chemoembolization (TACE) and
      percutaneous radiofrequency ablation (PRFA) for a small HCC measuring 2.5 cm in
      diameter. Enhanced magnetic resonance imaging (MRI) following treatment showed
      complete tumour necrosis and did not reveal the presence of a tumour around the
      treated area. Furthermore, the serum alpha-fetoprotein (AFP) level decreased at
      the completion of therapy. However, the HCC advanced in a very short time.
      Numerous tumours around the treated area were observed on enhanced computed
      tomography (CT) 50 days after PRFA. It is strongly suspected that the tumour was
      disseminated through the portal system because of the presence pattern of
      tumours. We believe this to be the first case illustrating a hepatic cancer that
      progressed rapidly following TACE and PRFA.

PMID- 11293453
TI  - Development of insulin-dependent diabetes mellitus in a patient with chronic
      hepatitis C during therapy with interferon-alpha.
AB  - Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis. It
      has been associated with various forms of autoimmune disease, e.g. autoimmune
      hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mellitus.
      Further, an increase of insulin resistance and development of non-insulin
      dependent diabetes mellitus has been described after treatment with IFN-alpha.
      Several studies have investigated the induction of different autoimmune markers
      by IFN-alpha, but only few specified patients who developed insulin-dependent
      diabetes mellitus. We report the case of a 37-year-old man with chronic hepatitis
      C who was treated with IFN-alpha plus ribavirin. Thirty weeks after the start of
      treatment, the patient developed insulin-dependent diabetes mellitus and therapy
      was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of
      diabetes mellitus, the C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml).
      The patient had a positive family history for type 2 diabetes. Several autoimmune
      markers were investigated before, during and 6 months after withdrawal of
      antiviral treatment. High titres of glutamic acid decarboxylase (GAD) antibodies
      were present before therapy. A significant increase in titres of islet cell
      antibodies, parietal cell antibodies and sperm antibodies was present after 14
      weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha therapy,
      these antibodies had significantly decreased whereas GAD antibodies remained
      unchanged. There was no clinical sign of any other autoimmune disease. Our data
      show that, in patients with a predisposition to insulin-dependent diabetes
      mellitus, the disease may become manifest as a side-effect during therapy with
      IFN-alpha. Several pathogenetic factors may be involved in this process, and, in
      addition to IFN-alpha, hepatitis C itself may induce autoimmune mechanisms. We
      conclude that screening for autoantibodies specific for type 1 diabetes should be
      performed before the start of IFN-alpha treatment. In patients found to be at
      increased risk of developing diabetes mellitus type 1, monitoring of titres of
      these antibodies during therapy could help to assess the individual risk-benefit
      ratio of IFN-alpha treatment.

PMID- 11293454
TI  - Conventional prostheses or self-expanding metal stents for malignant
      oesophagogastric obstruction?

PMID- 11293455
TI  - Helicobacter pylori colonization and immunological disease.

PMID- 11293456
TI  - The sensitization and differentiation of dimensions during category learning.
AB  - The reported experiments explored 2 mechanisms by which object descriptions are
      flexibly adapted to support concept learning: selective attention and dimension
      differentiation. Arbitrary dimensions were created by blending photographs of
      faces in different proportions. Consistent with learned selective attention,
      positive transfer was found when initial and final categorizations shared either
      relevant or irrelevant dimensions. Unexpectedly good transfer was observed when
      both irrelevant dimensions became relevant and relevant dimensions became
      irrelevant, and was explained in terms of participants learning to isolate one
      dimension from another. This account was further supported by experiments
      indicating that conditions expected to produce positive transfer via dimension
      differentiation produced better transfer than conditions expected to produce
      positive transfer via selective attention, but only when stimuli were composed of
      highly integral and spatially overlapping dimensions.

PMID- 11293457
TI  - Relation between confidence in yes-no and forced-choice tasks.
AB  - Yes-no and forced-choice tasks are common in psychology, but the empirical
      relation between reported confidence in the 2 tasks has been unclear. The authors
      examined this relation with 2 experiments. The general experimental method had
      participants first report confidence in the truth of each of many general
      knowledge statements (a yes-no task) then report confidence in them again when
      the statements were put into pairs where it was known that one statement was true
      and one was false (a forced-choice task). At issue was how confidence in the
      statements changed between the yes-no task and the forced-choice task. Two
      models, including the normative one, were ruled out as descriptive models. A
      linear model and a multiplicative model remain viable contenders.

PMID- 11293458
TI  - Perceiving, remembering, and communicating structure in events.
AB  - How do people perceive routine events, such as making a bed, as these events
      unfold in time? Research on knowledge structures suggests that people conceive of
      events as goal-directed partonomic hierarchies. Here, participants segmented
      videos of events into coarse and fine units on separate viewings; some described
      the activity of each unit as well. Both segmentation and descriptions support the
      hierarchical bias hypothesis in event perception: Observers spontaneously encoded
      the events in terms of partonomic hierarchies. Hierarchical organization was
      strengthened by simultaneous description and, to a weaker extent, by familiarity.
      Describing from memory rather than perception yielded fewer units but did not
      alter the qualitative nature of the descriptions. Although the descriptions were
      telegraphic and without communicative intent, their hierarchical structure was
      evident to naive readers. The data suggest that cognitive schemata mediate
      between perceptual and functional information about events and indicate that
      these knowledge structures may be organized around object/action units.

PMID- 11293459
TI  - Thematic relations in adults' concepts.
AB  - Concepts can be organized by their members' similarities, forming a kind (e.g.,
      animal), or by their external relations within scenes or events (e.g., cake and
      candles). This latter type of relation, known as the thematic relation, is
      frequently found to be the basis of children's but not adults' classification.
      However, 10 experiments found that when thematic relations are meaningful and
      salient, they have significant influence on adults' category construction
      (sorting), inductive reasoning, and verification of category membership. The
      authors conclude that concepts function closely with knowledge of scenes and
      events and that this knowledge has a role in adults' conceptual representations.

PMID- 11293460
TI  - Another source of individual differences: strategy adaptivity to changing rates
      of success.
AB  - This article explores an alternative approach to the study of individual
      differences of cognitive function-- that people may have the same strategies but
      differential ability to adaptively select among them in response to success and
      failure feedback from the environment. Three studies involving the complex and
      dynamic Kanfer-Ackerman Air Traffic Control Task (P. L. Ackerman & R. Kanfer,
      1994) demonstrate (a) that individuals do differ systematically along this
      strategy adaptivity dimension, (b) that those differences have important
      consequences for overall task performance, and (c) that the differences are
      primarily associated with reasoning ability and working-memory capacity.

PMID- 11293461
TI  - Suboptimality in human categorization and identification.
AB  - Categorization and identification decision processes were examined and compared
      in 4 separate experiments. In all tasks, the critical stimulus component was a
      line that varied across trials in length and orientation, and the optimal
      decision rules were always complex piecewise quadratic functions. Evidence was
      found that identification is mediated by separate explicit and implicit systems.
      In addition, a common type of suboptimality was found in both categorization and
      identification. In particular, observers apparently approximated the piecewise
      quadratic functions of the optimal decision rules with simpler piecewise linear
      functions. A computational model, which was motivated by a recent
      neuropsychological theory of category learning, successfully accounted for this
      suboptimal performance in both categorization and identification. The model
      assigns a key role to the striatum and assumes the observed suboptimality was
      largely due to massive convergence of visual cortical cells onto single striatal
      units.

PMID- 11293462
TI  - Cues trained apart compete for behavioral control in rats: convergence with the
      associative interference literature.
AB  - Contemporary theories of associative learning require cues be trained in compound
      for cue competition (interference) to occur. That is, Cues A and X should compete
      for behavioral control only if training consists of AX-outcome (O) trials and not
      if each cue is separately paired with O (i.e., X-O and A-O). Research with humans
      challenges this view by showing that A-O trials interpolated between training and
      testing of a X-O association impair responding to X (i.e., retroactive
      interference). In six conditioned suppression studies with rats, the authors
      demonstrate that two cues trained apart can each interfere with the potential of
      the other to predict the outcome. The authors conclude that this type of
      interference (a) reflects a failure to retrieve the target association due to
      priming at test of the interfering association and (b) is attenuated if the
      outcome is of high biological significance. These findings parallel previous
      reports in verbal learning research and suggest that a similar associative
      structure underlies some types of associations in nonverbal subjects.

PMID- 11293463
TI  - Nutritional selenium supplements: product types, quality, and safety.
AB  - Selenium supplements contain selenium in different chemical forms. In the
      majority of supplements, the selenium is present as selenomethionine. However, in
      multivitamin preparations, infant formulas, protein mixes, weight-loss products
      and animal feed, sodium selenite and sodium selenate are predominantly used. In
      some products, selenium is present in protein- or amino acid chelated forms; in
      still others, the form of selenium is not disclosed. Current evidence favors
      selenomethionine over the other forms of selenium. Extradietary supplementation
      of selenium at the dosage of 200 micrograms per day is generally considered safe
      and adequate for an adult of average weight subsisting on the typical American
      diet.

PMID- 11293464
TI  - In the midst of confusion lies opportunity: fostering quality science in dietary
      supplement research.
AB  - The Office of Dietary Supplements (ODS) was established at the National
      Institutes of Health (NIH) by Congress through the Dietary Supplement Health and
      Education Act (DSHEA) of 1994. The mission of the ODS is to strengthen knowledge
      and understanding of dietary supplements by evaluating scientific information,
      stimulating and supporting research, disseminating research results and educating
      the public, all in an effort to foster an enhanced quality of life and health for
      the U.S. population. In pursuit of this mission, ODS takes into account an array
      of dietary supplement ingredients and products. This includes vitamin and mineral
      supplements and botanicals, as well as non-nutrient supplements. Toward that end,
      ODS has taken a number of steps. In collaboration with other Institutes and
      Centers at NIH, ODS has established a network of Dietary Supplement Research
      Centers around the country that provide the focus for multidisciplinary research
      efforts; it supports research activities and scientific conferences, it supports
      evidence-based reviews of supplements, and it maintains a public database of
      scientific literature on dietary supplements. The lack of credible information
      from well-controlled studies of many dietary supplements raises issues of caution
      and concern. The ODS is committed to providing and disseminating accurate and
      reliable scientific information on dietary supplements.

PMID- 11293465
TI  - Assessment of body composition change in a community-based weight management
      program.
AB  - OBJECTIVE: The purpose of this study was to validate the use of the leg-to-leg
      bioelectrical impedance analysis (BIA) system in assessing change in body
      composition over 32 weeks in overweight and obese women participating in a
      community weight management program. DESIGN: Intervention, with subjects
      prescribed an energy-restriction diet and exercise program for 32 weeks and body
      composition measured pre-study and after 12 and 32 weeks. SUBJECTS AND SETTING:
      Overweight and obese premenopausal women (n=201) with no overt disease were
      recruited at six sites into community-based weight loss programs. One hundred and
      twenty-four women completed all aspects of the study. INTERVENTION: Energy intake
      was set at 0.8 x resting metabolic rate (RMR) for weeks 1 through 12, 1.0 x RMR
      for weeks 13 through 20 and 1.2 x RMR for weeks 21 through 32. Energy intake was
      based on a food exchange table, with the number of food exchanges adjusted to
      encourage a percent distribution of 55% carbohydrate, 30% fat and 15% protein.
      Subjects increased their daily walking distance by 3.2 km above pre-study levels.
      MEASURES OF OUTCOME: Underwater weighing, seven skinfolds, and leg-to-leg BIA
      tests were used to assess body composition. RESULTS: A 3 x 3 repeated measures
      ANOVA revealed no significant difference in detecting change in FFM at 12 and 32
      weeks among underwater weighing, BIA and skinfold, (F(4,492)=1.73, p=0.141)
      (decrease in FFM of 1.0+/-3.3 kg, 1.7+/-2.2 kg, and 1.4+/-3.3 kg respectively, 32
      weeks). CONCLUSIONS: The leg-to-leg BIA system provides a valid measure of body
      composition change in overweight premenopausal women during a 32-week community
      based weight loss program.

PMID- 11293466
TI  - The role of added sugars in the diet quality of children and adolescents.
AB  - OBJECTIVE: The associations between added sugars intake and consumption of
      vitamins, minerals and servings of foods in the USDA Food Guide Pyramid were
      examined. METHODS: Data from the USDA 1994-96 Continuing Survey of Food Intakes
      by Individuals were used in multivariate regression analyses to assess the
      statistical and practical significance of added sugars intake for diet and
      nutrient adequacy. RESULTS: The association of added sugars with consumption of
      vitamins, minerals and servings of foods in the USDA Food Guide Pyramid was
      usually statistically significant. For the model of all individuals over two
      years of age, individuals who consume more added sugars are predicted to consume
      more grains, lean meat and iron and to consume fewer vegetables and fruits and
      less dairy, vitamin A, calcium and folates. Children who consume more added
      sugars are predicted to consume more grains, vitamin C, iron and folates and to
      consume less dairy. Adolescents who consume more added sugars are predicted to
      consume more grains, vitamin C and iron and less fruit. CONCLUSION: The
      associations, whether positive or negative, however, were always small from
      either a practical perspective or in comparison to the associations of other
      sources of energy.

PMID- 11293467
TI  - Types of dietary fat and risk of coronary heart disease: a critical review.
AB  - During the past several decades, reduction in fat intake has been the main focus
      of national dietary recommendations to decrease risk of coronary heart disease
      (CHD). Several lines of evidence. however, have indicated that types of fat have
      a more important role in determining risk of CHD than total amount of fat in the
      diet. Metabolic studies have long established that the type of fat, but not total
      amount of fat, predicts serum cholesterol levels. In addition, results from
      epidemiologic studies and controlled clinical trials have indicated that
      replacing saturated fat with unsaturated fat is more effective in lowering risk
      of CHD than simply reducing total fat consumption. Moreover, prospective cohort
      studies and secondary prevention trials have provided strong evidence that an
      increasing intake of n-3 fatty acids from fish or plant sources substantially
      lowers risk of cardiovascular mortality. In this article, we review evidence from
      epidemiologic studies and dietary intervention trials addressing the relationship
      between dietary fat intake and risk of CHD, with a particular emphasis on
      different major types of fat, n-3 fatty acids and the optimal balance between n-3
      and n-6 fatty acids. We also discuss the implications of the available evidence
      in the context of current dietary recommendations.

PMID- 11293468
TI  - Effects of a cereal rich in soluble fiber on body composition and dietary
      compliance during consumption of a hypocaloric diet.
AB  - OBJECTIVES: To investigate the effects of oats, a cereal rich in soluble fiber,
      on body composition changes and dietary compliance during consumption of a weight
      loss diet. METHODS: Subjects were 41 healthy men and women aged 18 to 78 years.
      Weight maintenance energy requirements were established over two weeks during
      consumption of a control diet with low soluble fiber content. Subjects then
      consumed a hypocaloric diet for six weeks, either consuming a low soluble fiber
      control diet or a diet containing 45 g/1000 kcal rolled oats, a whole grain
      cereal rich in soluble fiber (mean energy deficit -895+/-18 kcal/day relative to
      weight maintenance energy requirements). Changes in body fat and fat-free mass
      were determined by underwater weighing, and dietary compliance was assessed using
      the urinary osmolar excretion rate technique. In a final phase of the study,
      subjects ate ad libitum for six months, and changes in body weight and
      composition were monitored. RESULTS: There was no significant effect of the oat
      containing diet on body weight or composition changes during the hypocaloric
      regimen or in the subsequent ad libitum period. In addition, fecal energy
      excretion was not significantly different between groups. However, there were non
      significant trends indicating reduced hunger in the oat group compared to
      controls (frequency of hunger 2.5+/-0.5 vs. 3.6+/-0.4, P=0.1). In addition, fewer
      oat subjects were non-compliant (four versus seven subjects dropped out or had
      urinary osmolar excretions greater than 130% of values predicted from dietary
      intake), but again the difference was not significant. CONCLUSIONS: These results
      suggest that use of a cereal rich in soluble fiber in a closely monitored
      hypocaloric feeding regimen does not improve weight loss or dietary compliance.
      Further studies are needed to examine the possibility that cereals containing
      soluble fiber may have effects on hunger and dietary compliance that could be
      important in less tightly controlled protocols than the one described here.

PMID- 11293469
TI  - Effect of alcohol on postprandial lipemia with and without preprandial exercise.
AB  - OBJECTIVE: Different factors such as exercise habits and alcohol consumption may
      modulate postprandial lipid metabolism. What are the effects of alcohol on
      postprandial metabolism in untrained and trained individuals? METHODS: The
      postprandial lipid response to an oral fat load (1 g fat per kg body weight (bw))
      with and without alcohol (0.5 g/kg bw) was evaluated in physically trained
      healthy young men (T, n = 12, mean +/- SD age 27 +/- 3 years. BMI 21.6 +/- 1.4
      kg/m2) after a premeal running session and in untrained healthy young men (UT, n
      = 8, age 24 +/- 1 years, BMI 23.2 +/- 1.8 kg/m2) without a premeal exercise
      session. The T subjects ingested 35.5 +/- 2.7 g alcohol, the UT subjects 38 +/-
      0.6 g. Fat was given as butter and the carbohydrates as marmalade and zwieback
      (rusk). The T subjects received 1.20 +/- 0.05 g fat and 1.02 +/- 0.04 g
      carbohydrates per kilogram lean body mass. The corresponding numbers for the UT
      subjects were 1.28 +/- 0.08 g and 1.20 +/- 0.06 g. The postprandial lipemia was
      observed for an eight-hour period. RESULTS: Alcohol led to an increase to the
      triacylglycerol area under the curve (AUC) in the T subjects from 7.4 +/- 0.4
      mmol/L * h on the control day to 11.3 +/- 0.9 mmol/L * h (p = 0.001). The
      corresponding numbers in the UT subjects were 13.4 +/- 2.3 mmol/L * h to 19.4 +/-
      3.5 mmol/L * h (p = 0.004). Alcohol intake and physical activity training were
      the major determinants of the triacylglycerol (TG) AUC in these subjects.
      CONCLUSION: The ingestion of a high fat meal in combination with alcohol leads to
      an increased in the postprandial lipemia independently from the level of
      training. It is suggested that this unfavorable effect of alcohol and a high fat
      diet could be modified by fat restriction or a combination of a premeal exercise
      session and a higher level of physical activity training.

PMID- 11293470
TI  - Iron and protein sufficiency and red cell indices in phenylketonuria.
AB  - OBJECTIVE AND METHODS: We reviewed records of 41 children with treated
      phenylketonuria (PKU) in order to evaluate hematopoiesis and the effect of iron
      and protein sufficiency. RESULTS: Six children (15%) were found to have anemia.
      Combined depletion of iron and protein stores was most likely to result in
      anemia, and two of the three children with this finding were anemic. Four
      children (10%) had evidence of iron deficiency without anemia (a precursor stage
      of iron deficiency anemia). Clinically significant iron depletion was found in
      older as well as younger children (well beyond the traditional infant/toddler
      deficient years). Plasma albumin was normal in all children and was not
      adequately sensitive to detect protein depletion sufficient to cause anemia or
      decreased growth. However, low plasma prealbumin (a more sensitive marker of
      protein sufficiency) correlated significantly with altered hematopoiesis or poor
      growth. CONCLUSION: Compared to non-affected individuals, children with treated
      PKU make fewer red cells that have normal volume but increased hemoglobin per
      cell, resulting in a lower calculated hematocrit when measured by electronic cell
      counting. In the presence of iron or protein depletion, anemia may result.
      Routine monitoring of ferritin, complete blood counts and prealbumin are
      recommended for children with PKU at all ages.

PMID- 11293471
TI  - Skin wrinkling: can food make a difference?
AB  - OBJECTIVES: This study addressed whether food and nutrient intakes were
      correlated with skin wrinkling in a sun-exposed site. METHODS: 177 Greek-born
      subjects living in Melbourne (GRM), 69 Greek subjects living in rural Greece
      (GRG), 48 Anglo-Celtic Australian (ACA) elderly living in Melbourne and 159
      Swedish subjects living in Sweden (SWE) participating in the International Union
      of Nutritional Sciences IUNS "Food Habits in Later Life" study had their dietary
      intakes measured and their skin assessed. Food and nutrient intakes were assessed
      using a validated semi-quantitative food frequency questionnaire (FFQ). Skin
      wrinkling was measured using a cutaneous microtopographic method. RESULTS: SWE
      elderly had the least skin wrinkling in a sun-exposed site, followed by GRM, GRG
      and ACA. Correlation analyses on the pooled data and using the major food groups
      suggested that there may be less actinic skin damage with a higher intake of
      vegetables (r(s)=-0.31, p<0.0001), olive oil (r(s)=-0.29, p<0.0001), fish (r(s)=
      0.24, p<0.0001) and legumes (r(s)=-0.16, p<0.0001), and lower intakes of butter
      (r(s)=0.46, p<0.0001) and margarine (r(s)=0.24, p<0.001), milk products
      (r(s)=0.16, p<0.01) and sugar products (r(s)=0.12, p<0.01). Similar findings were
      obtained using regression analyses, except fish was no longer significant; 32% of
      the variance for actinic skin damage was predicted by six out of the ten major
      food groups. In particular, a high intake of vegetables, legumes and olive oil
      appeared to be protective against cutaneous actinic damage (collectively
      explaining 20% of the variance); a high intake of meat, dairy and butter appeared
      to be adverse (explaining <5% of the variance). Prunes, apples and tea explained
      34% of variance amongst ACA. CONCLUSION: This study illustrates that skin
      wrinkling in a sun-exposed site in older people of various ethnic backgrounds may
      be influenced by the types of foods consumed.

PMID- 11293472
TI  - The influence of nutrition on IGF-1 in tube-fed profoundly retarded adults.
AB  - OBJECTIVE: This study was conducted to determine whether IGF-I concentrations are
      low in nonambulant profoundly retarded adults and to identify associated
      nutritional factors. METHODS: Serum IGF-I, albumin, pre-albumin, creatinine, zinc
      (Zn) and plasma amino acids were measured before and after a four-week 25%
      increase in formula in 25 individuals, divided into those fed by day (Group A) or
      by night (Group B). RESULTS: Circulating IGF-I was low in nine of the 22 subjects
      (40.9%) included in the analysis. Mean IGF-I increased 10.4% (p=0.004). Despite
      high intakes of essential amino acids and Zn, initial mean plasma tryptophan and
      phenylalanine were low, and serum Zn was low in 40.9% of subjects. Plasma
      tryptophan was low at both samplings and correlated with circulating IGF-I
      concentrations (p=0.02) at the beginning of the study. Serum IGF-I and Zn also
      correlated (p=0.02) initially. CONCLUSIONS: IGF-I is commonly low in this
      population and is associated with low plasma amino acid and Zn concentrations,
      despite high intakes of these nutrients. The causes and clinical implications of
      these abnormalities need further study.

PMID- 11293473
TI  - The effect of different dosages of guar gum on gastric emptying and small
      intestinal transit of a consumed semisolid meal.
AB  - BACKGROUND: There is no consensus about the effect of guar gum supplementation on
      gastrointestinal transit. It has been suggested that guar gum slows gastric
      emptying and intestinal transit, thus inducing an increased feeling of satiety.
      OBJECTIVE: To investigate whether addition of guar gum to a semisolid meal
      affects gastrointestinal transit. DESIGN: Eight male subjects were randomly
      studied four times. They consumed a standard semisolid test meal containing
      either 0 g, 2.5 g, 3.5 g, or 4.5 g of guar gum. The test meals contained 1 mCi
      99mTc-hepatate for scintigraphy and 5 g lactulose for the H2-breath test.
      Scintigraphic scanning was performed for at least two hours, and gastric half
      emptying time (T1/2) was calculated. Breath samples were collected at 15 minute
      intervals and analyzed for H2-enrichment. The orocecal transit time (OCTT) was
      then determined. A parameter of intestinal transit (PIT) was obtained by
      subtracting the T1/2 from the OCTT. RESULTS: There were no significant
      differences (in minutes) between the different tests in both T1/2 (0 g, t = 88.2
      +/- 11, 2.5 g, t = 83.3 +/- 11.9, 3.5 g, t = 83.3 +/- 13.6, 4.5 g, t = 72.4 +/-
      7.2, p = 0.86) and PIT (0 g, t = 149.9 +/- 26.6, 2.5 g, t = 145.5 +/- 25.6, t =
      3.5 g, t = 175.3 +/- 17.6, t = 4.5 g, t = 152.6 +/- 22.4, p = 0.52). CONCLUSION:
      Addition of guar gum to a semisolid meal up to a dosage of 4.5 g does not affect
      gastrointestinal transit. Other mechanisms than gastrointestinal motility are
      involved in a possible satiating effect of guar gum supplementation.

PMID- 11293474
TI  - Comparative free amino acid profiles of human milk and some infant formulas sold
      in Europe.

PMID- 11293475
TI  - Egg yolks are not OK even though they don't raise fasting lipids much.

PMID- 11293476
TI  - Cytokine responses to recombinant cholera toxin B subunit produced by Bacillus
      brevis as a mucosal adjuvant.
AB  - We attempted to clarify the mechanism of the mucosal adjuvanticity of recombinant
      cholera toxin B subunit (rCTB), which is inherently uncontaminated with the
      holotoxin produced by Bacillus brevis and has a powerful mucosal adjuvant
      activity, on cytokine responses compared with that of cholera toxin (CT). rCTB
      had no ability to stimulate cyclic AMP formation in mouse peritoneal macrophages
      (Mphi). Cytokine production by non-immunized Mphi cultured with rCTB or CT and by
      the spleen cells of mice co-immunized intranasally with ovalbumin (OVA) and rCTB
      or CT was examined. rCTB alone did not induce interleukin (IL)-1alpha/beta or IL
      6 production by Mphi, but combination of rCTB with lipopolysaccharide (LPS)
      enhanced both IL-1alpha/beta production. Conversely, CT plus LPS suppressed IL
      1alpha/beta production more than LPS alone. Both rCTB and CT suppressed IL-12
      secretion induced by interferon gamma (IFN gamma) plus LPS. IL-2, IL-4, IL-5, and
      IL-10 were secreted by mouse spleen cells restimulated with OVA after intranasal
      co-administration of OVA together with rCTB, and in response to CT, the same
      cytokines were secreted. The different effect of rCTB on Mphi from that of CT may
      mean a difference between the mechanisms of rCTB and CT during the early stage of
      an immune response.

PMID- 11293477
TI  - Role of furin in delivery of a CTL epitope of an anthrax toxin-fusion protein.
AB  - Anthrax toxin lethal factor (LF) in combination with anthrax toxin protective
      antigen (PA) was endocytosed and translocated to the cytosol of mammalian cells.
      Residues 1-255 of anthrax toxin lethal factor (LFn) was fused to a cytotoxic T
      lymphocyte (CTL) epitope of an influenza virus. For processing the toxins, PA
      must be cleaved into a 63-kDa fragment (PA63) by furin, which is a subtilisin
      like processing endo-protease expressed by many eukaryotic cells. To test the
      ability of cells treated with the LFn fusion protein plus PA to deliver the
      epitope, CTL assay was performed. Two types of cell lines were identified, one
      was able to deliver CTL epitope while the other failed to efficiently deliver the
      epitope. To further elucidate the differences between these cells, the role of
      furin in these cells was examined. Disruption of the furin gene reduced its
      ability to deliver the CTL epitope. Furin expression in cells capable of
      efficiently delivering CTL epitope was quantitatively higher than in cells unable
      to deliver the epitope. The results suggest that furin plays a critical role in
      delivery of the CTL epitope of LFn fusion protein.

PMID- 11293478
TI  - RAPD- and actA gene-typing of Listeria monocytogenes isolates of human
      listeriosis, the intestinal contents of cows and beef.
AB  - Seventy-five L. monocytogenes isolates of human listeriosis, the intestinal
      contents of cows and beef were divided into 5 major clusters, 17 sub-clusters and
      28 minor clusters by typing using random amplification of polymorphic DNA (RAPD).
      According to their major RAPD category, L. monocytogenes isolates serotyped as
      1/2b and 4b were distinguished from L. monocytogenes isolates of serovars 1/2a
      and 1/2c. Moreover serovar 4b was distinguished from serovar 1/2b by a difference
      in the RAPD sub-cluster category. All L. monocytogenes were found to possess
      either actA gene Type I or II, and only one actA gene type was detected in each
      RAPD minor cluster. actA gene Type II was observed in 32.0%, 38.5% and 18.9% of
      isolates from humans, cows and beef, respectively, and was detected more
      frequently in serovar 4b (46.9%) than in serovars 1/2a (22.2%), 1/2b (7.7%) and
      1/2c (0.0%). Twenty (80%) of 25 human isolates fell within three minor RAPD types
      (II-d (16%), V-p-1 (36%), V-p-2 (28%)). Two isolates from humans and beef were
      found to have the same RAPD type (Type IV-k-1), actA gene type (Type I) and
      serovar (1/2b). Our results suggest that only a few genotypes of L. monocytogenes
      are predominant in human listeriosis in Japan, although the human isolates were
      collected over a broad span of time and a wide geographical range. Our results
      also suggest that RAPD-, actA gene- and sero-typing can be useful for
      epidemiological analysis.

PMID- 11293479
TI  - Identification and characterization of the sodA genes encoding manganese
      superoxide dismutases in Vibrio parahaemolyticus, Vibrio mimicus, and Vibrio
      vulnificus.
AB  - Sequencing of Fur titration assay-positive clones obtained from genomic DNA
      libraries of Vibrio parahaemolyticus, V. mimicus and V. vulnificus revealed open
      reading frames encoding proteins of 202, 205 and 202 amino acid residues,
      respectively. Each open reading frame was preceded by a predicted Fur box which
      overlaps a likely promoter with similarity to the -10 and -35 consensus sequence
      of Escherichia coli. The deduced amino acid sequences shared considerable
      homology with bacterial Mn-containing superoxide dismutases (MnSODs). Consistent
      with this, these Vibrio strains produced proteins with SOD activity resistant to
      inhibition by H2O2 and KCN only when grown under iron-limiting conditions. Primer
      extension analysis of the total RNA from these vibrios revealed iron-repressible
      expression of the genes. Furthermore, when grown under iron-limiting conditions,
      E. coli carrying a plasmid with each cloned gene overexpressed protein with the
      same electrophoretic mobility and insensitivity of SOD activity to H2O2 and KCN.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by N-terminal
      amino acid sequencing revealed that proteins (MnSODs) having N-terminal amino
      acid sequences consistent with those deduced from the corresponding genes were
      present in cell lysates of the vibrios grown under these iron-limited conditions.
      These results demonstrate that the genes cloned in this study are sodA homologs
      encoding MnSODs, whose expression is regulated by the iron status of the growth
      medium. PCR using a primer set based on the V. parahaemolyticus sodA sequence
      revealed the presence of homologous genes in certain other Vibrio species.

PMID- 11293480
TI  - A nested PCR assay to detect DNA in sera for the diagnosis of deep-seated
      trichosporonosis.
AB  - Deep-seated trichosporonosis caused by Trichosporon asahii has a high mortality
      rate and a very poor prognosis. New species-specific oligonucleotide primers for
      T. asahii were developed from a sequence analysis of rRNA genes that included the
      internal transcribed spacer regions. A nested PCR assay with specific primers was
      used to examine 11 serum samples from 7 patients, who were diagnosed with deep
      seated trichosporonosis histologically at autopsy. In addition, Trichosporon cell
      wall polysaccharide (PS) was detected by a latex agglutination (LA) test. Of 11
      samples, seven had a positive LA test, and T. asahii DNA was also detected with
      the nested PCR assay. Of the four samples in which PS antigen was not detected,
      the nested PCR of two samples was positive. Our new nested PCR assay may be used
      as an adjunct to conventional methods for diagnosing T. asahii infection.

PMID- 11293481
TI  - Vi-Suppressed wild strain Salmonella typhi cultured in high osmolarity is
      hyperinvasive toward epithelial cells and destructive of Peyer's patches.
AB  - Salmonella typhi GIFU10007-3 which lost a viaB locus on its chromosome became
      highly invasive in our previous study. To investigate the phenomenon, we
      controlled Vi expression in wild strain S. typhi GIFU10007, and studied the
      invasive phenotype both in vitro and in vivo. When the wild strain of S. typhi
      was cultured in 300 mM NaCl containing Luria-Bertani broth (LBH), the expression
      of Vi antigen was suppressed, but secretion of invasion proteins (SipC, SipB and
      SipA) was increased. In this condition, wild strain S. typhi became highly
      invasive toward both epithelial cells and M cells of rat Peyer's patches. When
      GIFU10007 was cultured under conditions of high osmolarity, the bacteria
      disrupted Peyer's patches and induced massive bleeding in these structures only
      20 min after inoculation into the ileal loop. In contrast, Vi-encapsulated wild
      strain GIFU10007 cultured under low osmolarity was not destructive, even after 60
      min. To understand the role of the type III secretion system under conditions of
      high osmolarity, we knocked out the invA and sipC genes of both GIFU10007 and
      GIFU10007-3. Neither invA nor sipC mutants could invade epithelial cells or M
      cells in a high osmolarity environment. Our data show that the highly invasive
      phenotype was only expressed when the wild strain S. typhi was cultured under
      high osmolarity, which induced a state of Vi suppression, and in the presence of
      the type III secretion system.

PMID- 11293482
TI  - Use of antiserum-coated latex particles for serotyping Streptococcus pneumoniae.
AB  - The Quellung reaction provides a standard means for serotyping Streptococcus
      pneumoniae, but it requires microscopic examination with skillful technique. We
      have developed an improved agglutination method with anti-rabbit IgG-coated latex
      particles, which are sensitized with pooled antisera for serotyping/serogrouping
      S. pneumoniae. Our method is as specific and sensitive as the Quellung test, and
      much easier to perform.

PMID- 11293483
TI  - First records of tick-borne pathogens, Borrelia, and spotted fever group
      Rickettsiae in Okinawajima Island, Japan.
AB  - In early April 2000, tick-borne pathogens were surveyed in the northern area of
      Okinawajima Island, Okinawa Prefecture, which is the southernmost area of Japan.
      Borrelia valaisiana, a Lyme disease spirochete, was isolated from a field mouse
      Mus calori, and unidentified rickettsiae of the spotted fever group were isolated
      from all stages of Amblyomma testudinarium. These are the first reports of these
      pathogens on Okinawajima Island.

PMID- 11293484
TI  - Molecular characterization in the VP7, VP4 and NSP4 genes of human rotavirus
      serotype 4 (G4) isolated in Japan and Kenya.
AB  - The VP7, VP4 and NSP4 genes of human rotavirus serotype 4 (G4) were analyzed to
      investigate intraserotypic variations. The techniques used included reverse
      transcription polymerase chain reaction with subtype specific primers,
      restriction fragment length polymorphism analysis and sequence analysis. Twelve
      isolates (nine from Japan and three from Kenya) and two standard strains (Hochi,
      Odelia) were G4A P[8] Wa group NSP4. A standard strain (ST3) was G4A P[6] Wa
      group NSP4 and a strain (VA70) was G4B P[8] Wa group NSP4. These results show G4
      rotaviruses can be divided into three combinations at the moment.

PMID- 11293485
TI  - A lack of consistent amino acid substitutions in NSP4 between rotaviruses derived
      from diarrheal and asymptomatically-infected kittens.
AB  - Nonstructural glycoprotein NSP4 of group A rotavirus has recently been shown to
      be a viral enterotoxin, inducing diarrhea in neonatal mice. Literature is
      conflicting as to whether there is any consistent amino acid substitution between
      virulent (or symptomatic) and attenuated (or asymptomatic) rotavirus strains. We
      have sequenced and compared the NSP4 sequences derived from a total of 10
      geographically- and serologically-related feline rotavirus strains from both
      diarrheal and asymptomatically-infected kittens. These NSP4 sequences were
      closely related to each other and there were differences at 19 amino acid
      residues, but none was segregated according to whether the strain was isolated
      from a diarrheal kitten or not. Thus, this study failed to lend support to the
      contention that mutations in NSP4 play a significant role in the pathogenesis of
      rotavirus diarrhea. Involvement of other genes may explain the outcome of
      infection in cats from which these 10 feline rotaviruses were isolated.

PMID- 11293486
TI  - Genomic map of Clostridium perfringens strain 13.
AB  - A physical and genetic map of Clostridium perfringens strain 13 was constructed.
      C. perfringens strain 13 was found to have a 3.1-Mb chromosome and a large 50-kb
      plasmid, indicating that strain 13 has a relatively small genome among C.
      perfringens strains. A total of 313 genetic markers were mapped on the chromosome
      of strain 13. Compared with the physical and genetic map of C. perfringens CPN50,
      strain 13 had a quite similar genome organization, but with a large deletion
      (approximately 400 kb) in a particular segment of the chromosome. Among several
      toxin genes, a beta2 toxin gene that is a novel virulence gene in C. perfringens
      was found to be located on the 50-kb plasmid.

PMID- 11293487
TI  - Oxidative stress effect on the activation of hepatic stellate cells.
AB  - Collagen is the most excessive extracellular matrix protein in hepatic fibrosis.
      Activated, but not quiescent, hepatic stellate cells (HSCs) have a high level of
      collagen and a smooth muscle actin (alpha SMA) expression. HSCs play a key role
      in the pathogenesis of hepatic fibrosis. We analyzed a mechanism leading to HSC
      activation by evaluating the role of oxidative stress and the expression of NFkB.
      In vitro study HSCs were proliferated (PCNA:2% vs 68%) and activated (alpha SMA:
      5% vs 78%) by ascorbate/FeSO4, and HSCs activated by type I collagen were blocked
      (PCNA: 97% vs 4%, a SMA: 86% vs 9%) by a-tocopherol. In vivo study means of a SMA
      positive cells in liver at 400 x HPF were 48.3+/-5.2 and 15.2+/-1.8 and
      [3H]thymidine uptake of HSC was 529.2+/-284.8 cpm and 223.0+/-86.3 cpm in control
      and a-tocopherol treated group respectively at 32 hours after CCl4 injection.
      Nuclear extracts from activated, but not from quiescent, HSCs formed a complex
      with the NFkB cognate oligonucleotidesand alpha-tocopherol inhibited this
      bindings. This study indicates that oxidative stress plays an essential role
      through the induction of NFkB on HSC activation.

PMID- 11293488
TI  - The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in
      bronchial asthma and allergic rhinitis.
AB  - Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness,
      but results at the moment are less than convincing. The present study was
      conducted to evaluate the effect of immunotherapy on the degree of nonspecific
      bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA)
      and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test,
      allergic skin test, serum IgE and peripheral blood eosinophil counts were
      performed before and after 12 months or more of immunotherapy. The improved
      group, as determined by a shift of at least two doubling concentrations of
      methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR
      (n=13). The geometric mean of the methacholine provocational concentration (PC20)
      changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA
      (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In
      conclusion, nonspecific bronchial hyperresponsiveness was improved by
      immunotherapy in three quarters of the allergic rhinitis cases and in about a
      half of the allergic bronchial asthma patients, which suggests that immunotherapy
      might be helpful at preventing the development of bronchial hyperresponsiveness
      in allergic rhinitis patients, and that it does not improve bronchial
      hyperresponsiveness in about a half of allergic bronchial asthma patients.

PMID- 11293489
TI  - Increase in rat plasma antioxidant activity after E. coli lipopolysaccharide
      administration.
AB  - It is well recognized that the sensitivity of animals to lipopolysaccharide (LPS)
      endotoxin varies tremendously. And, it has been recently observed that Sprague
      Dawley rats dramatically increase the activity of hepatic endogenous
      antioxidative enzyme systems after LPS administration. This finding suggests that
      the relative resistance of rats to LPS may be related to a concomitant increase
      in the activities of the hepatic antioxidant systems. This study was designed to
      examine if the above reported hepatic change in rats given LPS could be observed
      at the systemic level. Male Sprague-Dawley or Wistar rats, weighing 250 - 350 g,
      were given increasing doses (10 - 100 mg/kg) of LPS i.p. under 1.0% isoflurane
      anesthesia. Antioxidant capacity (AOC), blood gas analysis, and the
      cardiovascular parameters of the arterial blood of animals were determined over a
      4 hour period following LPS administration. In addition, we studied the effect of
      pretreatment with the non-specific nitric oxide synthase inhibitor, L-N(G)
      Nitroarginine methyl ester hydrochloride (L-NAME), given 50 mg/kg s.c. one and 24
      hours before the administration of 20 mg/kg LPS i.p. in Sprague-Dawley rats. Rats
      given sufficiently high doses of E. coli LPS to produce behavioral effects also
      showed increased plasma AOCs in the early period after the administration of LPS.
      Similar changes were noted in Sprague-Dawley and Wistar rat strains, but at
      different doses that reflect their differential sensitivities to the LPS induced
      inflammatory response. Also, the resistance of the Sprague-Dawley strain of rats
      to LPS was not altered by the prior administration of L-NAME, nor was the plasma
      AOC altered. In conclusion, our study suggests that the rat strains are
      relatively resistant to develop the toxic signs of LPS in the early period after
      the administration of LPS, especially in Sprague-Dawley rats. Moreover, endotoxin
      induced increases in plasma AOC may contribute to the rats' resistance to LPS
      intoxication.

PMID- 11293490
TI  - Extradural approach to the lateral sellar compartment.
AB  - This paper describes an extradural approach to the lateral sellar compartment
      (LSC, cavernous sinus), which represents a refinement of the original work
      performed on this topic by Parkinson, Dolenc, and Hakuba, and other enthusiastic
      neurosurgeons. This detailed description of the extradural approach is based on
      the dissection of 30 cadaver specimens and surgical experience of 110 LSC
      lesions. The extradural approach is based on the developmental anatomy of the
      LSC, and provides: (1) complete exposure of the entire LSC; (2) excellent control
      of the intracavernous carotid artery; (3) easier identification and less injury
      of the cranial nerves; (4) reduced brain damage with limited extradural
      retraction; (5) preserving the Sylvian vein and the sphenoparietal sinus; (6)
      minimal intradural blood spillage; (7) shorter operative time; (8) physiological
      reconstruction of the lateral wall to prevent CSF leakage; and (9) access to the
      contralateral LSC. As the LSC is an extradural space, the extradural approach may
      be safely employed to access lesions involving the LSC.

PMID- 11293491
TI  - Diffusion-weighted image and MR spectroscopic analysis of a case of MELAS with
      repeated attacks.
AB  - We report the clinical and MR manifestations of an 18 year-old girl with
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      (MELAS) syndrome. Recurrent status epilepticus caused reversible cytotoxic edema
      on diffusion-weighted images (DWI). Initial and one month follow-up MR
      spectroscopy, after seizure control, showed some discrepancies in the ratio of
      metabolites. N-acetylaspartate (NAA) partially recovered (NAA/creatine (Cr)
      ratio: 1.27-->1.84). This was because of a normalization of decreased NAA due to
      cellular dysfunction as a result of status epilepticus. A low ratio of NAA/Cr due
      to abnormal mitochondria remained in the decreased state. Reversible NAA/Cr
      ratios in the acute lesion suggested that NAA reflects the neuronal function as
      well as the level of neuronal structural damage. The altered NAA/Cr ratio better
      correlated with the abnormal signal intensity area of T2-weighted images (T2WI)
      and DWI than the lactate (Lac)/Cr ratio. With conservative treatment with anti
      epileptics not accompanied by coenzyme Q or sodium dichloroacetate, lactate
      persistently increased (Lac/Cr ratio: 1.01-->1.21) because of the continued
      production of lactate in cells with respiratory deficiency, which is the main
      pathology of MELAS.

PMID- 11293492
TI  - Development of glaucoma in the course of interferon alpha therapy for chronic
      hepatitis B.
AB  - Previous reported ocular complications of interferon alfa administration are
      extremely rare. These include oculomotor palsy, corneal allograft rejection,
      retinal hemorrhage and cotton wool patches. A 15-year-old boy with chronic
      hepatitis B was treated with interferon alpha for six months, and then developed
      glaucoma. After the interferon therapy had been discontinued the glaucoma
      improved. Accordingly, we report a case of glaucoma development during the course
      of interferon alpha therapy for chronic hepatitis B.

PMID- 11293493
TI  - An ischemic skin lesion after chemoembolization of the right internal mammary
      artery in a patient with hepatocellular carcinoma.
AB  - A huge nodular hepatocellular carcinoma located at the anterior superior portion
      of the left lobe in a patient with hepatocellular carcinoma was treated with
      transcatheter arterial chemoembolization through the left hepatic artery. Three
      months later, however, there was a re-elevation of the serum alpha-fetoprotein
      level and evidence of a marginal recurrence at the left side of the previously
      embolized tumor was noted on the postembolization computed tomographic scan.
      Although the hepatic artery was intact in the second hepatic arteriography, we
      found that the right internal mammary artery was feeding the recurred
      hepatocellular carcinoma. This internal mammary artery was successfully treated
      with Lipiodol-transcatheter arterial chemoembolization. However, an ischemic
      lesion occurred in the skin of the anterior chest and abdominal wall several days
      after internal mammary artery embolization. We report here a very rare case of
      ischemic skin lesion on the anterior chest and abdominal wall following
      transcatheter arterial chemoembolization of the right internal mammary artery.
      This internal mammary artery was embolized because it had developed a collateral
      tumor feeding vessel following the initial chemoembolization of a hepatocellular
      carcinoma.

PMID- 11293494
TI  - Evaluation of the NMP22 test and comparison with voided urine cytology in the
      detection of bladder cancer.
AB  - The purpose of this study was to assess the clinical performance of the NMP22
      test and to compare it with that of voided urine cytology for the detection of
      bladder cancer. The NMP22 test was evaluated in two groups of patients. The first
      group was comprised of patients with histologically confirmed active transitional
      cell carcinoma (TCC) of the bladder, and the second group contained those with a
      history of bladder TCC but that were considered to have no evidence of disease on
      the basis of cystoscopic evaluation of bladder and/or biopsy. Sensitivity was
      determined in voided urine samples from patients with active TCC of the bladder.
      Specificity was determined in the urine samples of patients with a history of
      bladder TCC but no current evidence of disease. The NMP22 test was positive in 53
      of 70 samples from patients with active bladder TCC. The sensitivity of the NMP22
      test (75.7%) is significantly better than that of voided urine cytology (55.7%).
      The specificity of the NMP22 test and of voided urine cytology were 72.2% and
      88.9% respectively, in patients with a history of bladder TCC but no current
      evidence of disease. There was no significant difference between the specificity
      of NMP22 and that of urine cytology. The NMP22 test is superior to voided urine
      cytology in the detection of TCC of the bladder. The results of this study
      indicate that the NMP22 test is an useful adjunct to cystoscopy in the detection
      and monitoring of TCC of the bladder.

PMID- 11293495
TI  - Classical malignant rhabdoid tumor of central nervous system in 9-year-old
      Korean.
AB  - A Malignant rhabdoid tumor (MRT) arising in the right temporoparietal lobe of a 9
      year-old boy is described along with the results of an immunohistochemical study.
      The patient initially sought medical attention for a ptosis and right sided
      headache. The child underwent a subtotal resection of the tumor, followed by
      radiotherapy and systemic chemotherapy, but died three years after surgery. A
      MRT, a primary neoplasm of the central nervous system (CNS), is an entity of
      unknown histogenesis with a dismal prognosis, which only occurs in early
      childhood. Histologically similar tumors with more varied morphological features
      have been designated as an atypical teratoid/rhabdoid tumor. However, a classical
      MRT is extremely rare in the CNS and our case represents a classical CNS MRT.

PMID- 11293496
TI  - Lower gastrointestinal bleeding due to cytomegalovirus ileal ulcers in an
      immunocompetent man.
AB  - Cytomegalovirus (CMV) infections are commonly reported in severely
      immunocompromised hosts and ulcers of the alimentary tract are frequently
      observed in systemic CMV infections. However, invasive and ulcerative disease of
      the gastrointestinal (GI) tract caused by CMV has also been reported in healthy
      adults. Many reports show that a CMV infection can produce localized ulcerations
      in the esophagus, stomach, small intestine, and colon in nonimmunocompromised
      individuals. The most common site of involvement by CMV infection in the GI tract
      is the colon followed by the upper GI tract and the least common site is the
      small intestine. Although GI bleeding is one of the major presenting symptoms of
      patients with CMV infections of the GI tract, lower GI bleeding due to CMV ileal
      ulcers in immunocompetent patients, to our knowledge, has not been reported in
      the English literature. Recently, we experienced a case of lower GI bleeding due
      to CMV ileal ulcers in a 57-year-old man who had no evidence of immunocompromise.
      This case suggests that small intestinal ulcers due to CMV infection should be
      included in the differential diagnosis of lower GI bleeding even in
      immunocompetent hosts.

PMID- 11293497
TI  - A challenge for reform in South Korea.

PMID- 11293498
TI  - Methylphenidate increased regional cerebral blood flow in subjects with attention
      deficit/hyperactivity disorder.
AB  - The regional cerebral blood flow (rCBF) responses to methylphenidate (MPH)
      treatment were examined in children with attention deficit/hyperactivity disorder
      (ADHD). Thirty-two male children, diagnosed with ADHD by the DSM-IV diagnostic
      criteria, other behavioral assessment scales and neuropsychological battery, were
      studied using 99mTc-HMPAO-single photon emission computed tomography (SPECT).
      Subjects were studied before and after MPH treatment. First, using an image
      subtraction method, we obtained a NDR parametric image of each patient and found
      increased cerebral blood flow in the frontal lobes, caudate nuclei and thalamic
      areas after treatment. When the changes in SPECT and clinical response were
      compared, the matching rate, sensitivity and specificity between them were found
      to be 77.1, 80.0 and 79.2%, respectively. Second, three transaxial brain slices
      delineating anatomically defined regions of interest (ROI) at 20, 40, and 60mm
      above the orbitomeatal line (OML) were used, with the average number of counts
      for each region of interest normalized to the area of the cerebellar maximal
      uptake. The left and right prefrontal areas, and caudate and thalamic areas
      showed significant increases in rCBF after MPH treatment. These findings
      suggested MPH could affect the function of the fronto-striato-thalamic circuit,
      which is known as the pathophysiologic site of ADHD and could be used to correct
      the underlying brain dysfunction of ADHD.

PMID- 11293499
TI  - Studies on the changes of c-fos protein in spinal cord and neurotransmitter in
      dorsal root ganglion of the rat with an experimental peripheral neuropathy.
AB  - Animal models for human chronic pain syndromes have been developed and widely
      used for pain research. One of these neuropathic pain models by Kim and Chung
      (1992) has many advantages for operation and pain elicitation. In this
      neuropathic model we have examined the c-fos protein, substance P, CGRP
      immunoreactivity in dorsal root ganglia and dorsal horn. 50 Sprague-Dawley rats
      were used for this study. L5 and L6 spinal nerves were ligated tightly to produce
      the neuropathic pain model. After 2, 4, 8, 16, and 24 hours and 1 week of
      surgery, rats were anesthetized and sacrificed by perfusion. After confirmation
      of the roots transected by the surgery, the L5 and L6 dorsal root ganglions and
      spinal cord were removed and processed for immunohistochemistry. All tissue
      sections were immunohistochemically stained for substance P, CGRP and c-fos using
      the peroxidase-antiperoxidase (PAP) method. The number of immunostained substance
      P and CGRP dorsal root ganglion cells and c-fos immunoreactive dorsal horn cells
      were counted and analyzed statistically with Mann-Whitney U test. The results are
      as follows. The number of c-fos protein immunoreactive neurons in the superficial
      layer of dorsal horn were increased markedly 2 hours after operation, and
      gradually decreased to normal level 1 week after operation. The number of c-fos
      protein immunoreactive neurons in the deep layer of the dorsal horn gradually
      increased to a peak 24 hours after operation, then decreased to the normal level
      1 week after operation. The number of substance P and CGRP immunoreactive L5 and
      L6 dorsal root ganglion neurons were decreased markedly 1 week after the pain
      model operation. In conclusion, after neuropathic pain model operation, c-fos
      proteins were immediately expressed in the superficial layer of spinal dorsal
      horn, thereafter c-fos proteins in the deep layer of spinal dorsal horn were
      expressed. CGRP and substance P immunoreactive neurons in DRG were decreased
      markedly 1 week after neuropathic pain model operation. These decrements do not
      coincide with the other chronic pain models, which show great increases in these
      pain transmitting substances. Therefore, the relationship between pain and c-fos,
      SP and CGRP should be investigated further.

PMID- 11293500
TI  - Differentiation between reinfection and recrudescence of helicobacter pylori
      strains using PCR-based restriction fragment length polymorphism analysis.
AB  - The aim of this study was to evaluate whether PCR-based restriction fragment
      length polymorphism (RFLP) analysis was effective in differentiating between
      reinfection and recrudescence of H. pylori strains. Following a 1-2 week regimen
      of omeprazole 20 mg, amoxicillin 1.0 g, and clarithromycin 500 mg twice daily,
      twenty patients with duodenal ulcer were enrolled in the study. Ten patients
      (group 1, control) were not successfully treated, and another 10 patients (group
      2) exhibited recurrence of infection 6-24 months following the therapy. Follow-up
      diagnosis was performed by Giemsa stain and CLO test. RFLP profiles of antral and
      midbody biopsy specimens were compared before and after therapy. PCR products
      using the ureC gene were digested with restriction enzymes Hha I, Mbo I, and Hind
      III, and the fragments generated were analyzed by agarose gel electrophoresis.
      Hha I, Mbo I, and Hind III digestion produced 13, 7, and 2 distinguishable
      digestion patterns, respectively. There was no difference in RFLP profiles seen
      before and after the therapy in 17 duodenal ulcer patients, while different RFLP
      profiles were discovered in 3 patients. Following treatment, one (group 2)
      patient differed in Mbo I, and two (one each from both groups) patients differed
      in Hha I and Mbo I RFLP patterns. Eight of group 2 patients showed recrudescence
      of previous infection and two patients had reinfection by another strain. This
      study supports the hypothesis that PCR-based RFLP analysis can be effective for
      differentiating reinfection and recrudescence of H. pylori strains following
      triple therapy.

PMID- 11293501
TI  - Clinicopathologic study of Wegener's granulomatosis with special emphasis on
      early lesions in 10 Korean patients.
AB  - We reviewed ten cases of Wegener's granulomatosis with special emphasis on the
      characteristics of the early stage of Wegener's granulomatosis. All patients
      presented with nonspecific symptoms and signs, so that Wegener's granulomatosis
      was not initially considered. However, half of the patients had clinical or
      radiologic disease in the nose/or paranasal sinuses as the primary presenting
      problems and showed neutrophil microabscess surrounded by palisading epithelioid
      cells and irregularly arranged giant cells in the nasal biopsy as the most
      characteristic feature. Five of ten patients were believed to have a protracted
      superficial phenomenon before involvement of other organs, specifically the lung
      or kidney. Four of ten patients showed nonreactivity to ANCA test at the time of
      presentation. Although the number of cases reviewed in this study was small, the
      rate of nonreactivity to ANCA was higher than those of the larger series. The
      importance of early diagnosis of Wegener's granulomatosis can not be
      overemphasized in view of the fact that cases unrecognized clinicopathologically
      finally progress to full-blown systemic form of Wegener's granulomatosis with
      poor prognosis. The diagnosis of Wegener's granulomatosis should be based on a
      thorough and meticulous examination of its characteristic histologic changes in
      biopsied tissue particularly extravascular foci.

PMID- 11293502
TI  - Hyperfractionated re-irradiation using a 3-dimensional conformal technique for
      locally recurrent carcinoma of the nasopharynx; preliminary results.
AB  - To evaluate the efficacy of hyperfractionated re-irradiation using a three
      dimensional conformal radiotherapy (3-D CRT) technique in patients with locally
      recurrent carcinoma of the nasopharynx. Four patients with locally recurrent
      nasopharyngeal cancer were retreated with a hyperfractionated schedule using a 3
      D CRT technique. Re-irradiation was delivered in 1.1-1.2 Gy fractions twice per
      day (BID), with interfraction intervals of more than 6 hours. The total dose
      ranged from 59.4 to 69.2 Gy. A 3-D CRT technique with 5- or 6-field coplanar
      and/or non-coplanar beams were employed during the entire treatment procedure.
      All four patients achieved complete remission of locally recurrent lesions, with
      marked improvement of subjective symptoms, immediately after re-irradiation. All
      are alive and well without evidence of disease after limited follow-up periods,
      which range from 7 to 20 months. So far, there have been no radiation-induced
      neurologic complications. Four patients with locally recurrent carcinoma of the
      nasopharynx were successfully treated by hyperfractionated re-irradiation using a
      3-D CRT technique. A relatively high re-irradiation dose of more than 60 Gy may
      be safely delivered with no serious acute or late radiation-induced complications
      in patients with local recurrences and who were initially treated with doses
      greater than 70 Gy.

PMID- 11293503
TI  - Transplantation of peripheral blood stem cells mobilized by intensified
      consolidation and granulocyte colony-stimulating factor in acute leukemia.
AB  - The purpose of this study was to evaluate the feasibility and efficacy of
      autologous transplantation of peripheral blood stem cells (PBSC) mobilized with
      high-dose consolidation chemotherapy and granulocyte colony-stimulating factor in
      patients with acute myelogenous leukemia (AML). Twenty patients received
      myeloablative chemotherapy or chemo-radiotherapy including total body irradiation
      followed by the infusion of PBSC. PBSC were collected by large-volume
      leukaphereses. The mean number of mononuclear cells and CD34-positive cells
      infused were 7.2 x 10(8)/kg (range, 2.2-16.6), and 6.6 x 106/kg (range, 2.1
      27.7), respectively. Engraftment failure was not seen in the enrolled patients.
      The median time to neutrophil (> or = 500/microL) and platelet recovery (> or =
      50,000/microL) from the transplant was 12 days (range, 8-20) and 28 days (range,
      10-600), respectively. The 2-year probability of disease-free survival (DFS) and
      relapse were 43% and 57% for patients with AML transplanted in first complete
      remission (CR1). The outcome of the patients transplanted in the advanced status
      was significantly worse than the patients transplanted in CR1 (P=0.04). Most
      relapses occurred within 1 year after transplantation. Fatal hepatic veno
      occlusive disease was observed in one case. Other transplantation-related
      toxicities were mild. Our results demonstrated that autologous transplantation of
      high-dose consolidation chemotherapy-mobilized peripheral blood progenitor cells
      is feasible in the patients with AML in CR1. To further reduce the risk of
      leukemia relapse, much effort should be contributed to the field of ex vivo
      purging and post-transplant immunotherapy.

PMID- 11293504
TI  - Effects of iontophoretically applied substance P, calcitonin gene-related peptide
      on excitability of dorsal horn neurones in rats.
AB  - Spontaneous pain, allodynia and hyperalgesia are well known phenomena following
      peripheral nerve or tissue injury, and it is speculated that secondary
      hyperalgesia and allodynia, are generally thought to depend on a
      hyperexcitability (sensitization) of neurons in the dorsal horn. It is supposed
      that the sensitization may be due to various actions of neurotransmitters (SP,
      CGRP, excitatory amino acids) released from the primary afferent fibers. In this
      study, we examined effects of the iontophoretically applied SP and CGRP on the
      response to EAA receptor agonists (NMDA and non-NMDA) in the WDR dorsal horn
      neurones and see if the effects of SP or CGRP mimic the characteristic response
      pattern known in various pain models. The main results are summarized as follows:
      1) SP specifically potentiated NMDA response. 2) CGRP non-specifically
      potentiated both NMDA and AMPA responses. Potentiation of NMDA response, however,
      was significantly greater than that of AMPA response. 3) 50% of SP applied cells
      and 15.8% of CGRP applied cells showed reciprocal changes(potentiation of NMDA
      response and suppression of AMPA response). These results are generally
      consistent with the sensitization characteristics in diverse pain models and
      suggests that the modulatory effects of SP and CGRP on NMDA and non-NMDA (AMPA)
      response are, at least in part, contribute to the development of sensitization in
      various pain models.

PMID- 11293505
TI  - Evaluation of diagnostic methods of re-emerging malaria in Korean patients.
AB  - Malaria is one of the most important parasitic diseases especially in tropical
      areas. Over 300 million people are affected and the condition causes 1-3 million
      deaths each year. It is transmitted by the bite of infected Anopheles mosquitoes.
      Although Korea was declared to be free of Malaria by the WHO in 1979, malaria re
      emergence has been apparent since 1993 amongst soldiers located near the De
      Militarized Zone (DMZ) in the northern part of the country. Conventional
      microscopic examination of thin and thick blood films demonstrates the presence
      of the parasite and thus this method has been used to confirm the diagnosis of
      malaria, but it is a labor-intensive procedure and relies upon subjective
      interpretation. To overcome these limitations, fast and reliable methods for
      malaria detection have been recently introduced. In this study, we compared three
      kinds of antibody detection kits and one biochemical test kit that determines the
      presence of Plasmodium lactate dehydrogenase (pLDH) with conventional peripheral
      blood smears. The antibody detection methods examined were, two rapid test pack
      format methods and a single microplate format enzyme-linked immunosorbent assay
      (ELISA) kit, as manufactured by Korean companies. The sensitivities of the three
      commercial antibody detection kits in the early stage of malaria were 70.8%,
      77.4%, and 63.6%, their corresponding specificities 90.5%, 91.8%, and 80.9%, and
      their accuracies 87.6%, 87.0%, and 76.7%. The sensitivity and specificity of the
      pLDH assay were 100% apiece and the results were in 100% concordance with the
      microscopy of thick blood films. Thus, the pLDH assay may be used as an
      alternative for conventional microscopic blood film examination, especially in
      emergency situations when prompt treatment is necessary.

PMID- 11293506
TI  - The central conduction time in posterior tibial and pudendal nerve somatosensory
      evoked potentials.
AB  - The somatosensory evoked potentials (SEPs), following stimulation of both the
      posterior tibial nerve (PTSEP) and pudendal nerve (PNSEP), comprise of the lumbar
      negative, subcortical and cortical potential. These can be used to assess the
      long somatosensory pathway, including peripheral, intraspinal and intracranial
      conduction along the entire length. This study aimed to compare the central
      conduction time between the PTSEP and the PNSEP, and to investigate the
      relationship between the intraspinal and intracranial conduction time in the SEP
      pathway. The SEPs following stimulation of the posterior tibial nerve at the
      ankle and the pudendal nerve at the shaft of the penis were analyzed in 20 normal
      male subjects. The central conduction of the PNSEP was found to be slower than
      that of the PTSEP (p <0.05). This difference is due to a delay in conduction
      rather than that of intracranial conduction.

PMID- 11293507
TI  - Ovalbumin fused with diphtheria toxin protects mice from ovalbumin induced
      anaphylactic shock.
AB  - For those with allergy, vaccination with a specific allergen has often been used
      as a major therapeutic measure. However, the universal application of this
      technique in clinics have been restricted due to its low success rates and the
      risk of active systemic anaphylactic shock (ASAS). In this regard, we constructed
      a fusion protein (OVA-DT), ovalbumin (OVA) fused with diphtheria toxin protein
      (DT), which may exert a specific cytotoxicity to cells bearing OVA-specific IgE.
      Its therapeutic effect was evaluated in mice (BALB/c) sensitized with OVA (Os
      mice). OVA challenges to the OVA-sensitized mice (Os-mice) caused ASAS to death
      within 30 min, but OVA-DT treatment afforded mice complete protection. When OVA
      DT was treated to the Os-mice, none showed the signs of ASAS when re-challenged
      48 h after the treatment. OVA-DT itself was not found to be toxic or allergenic
      in normal mice. The effect of OVA-DT on the biological functions of mast cells
      was also studied. Binding of OVA-DT to OVA-specific IgE bearing mast cells and
      the inhibition of histamine release from these cells were observed. In addition,
      OVA-DT treatment inhibited the proliferation of OVA-specific B cells in mice. In
      Os-mice treated with OVA-DT, levels of anti-OVA IgG2a in serum and the production
      of IFN-gamma by splenic lymphocytes were found to increase, but the production of
      IL-4 by these cells decreased. Re-direction of cytokine profiles from OVA
      specific Th2 to OVA-specific Thl is suggested. These results indicate that OVA-DT
      can protect Os-mice from ASAS due to OVA challenge, because it inactivates OVA
      specific IgE-expressing cells, including mast cells and B cells.

PMID- 11293508
TI  - The fullness of who we are.

PMID- 11293509
TI  - The fate of the fibrous capsule after saline implant removal.
AB  - After removal of a silicone breast implant, if a capsulectomy is not performed,
      the residual capsule may persist, become calcified, and appear on routine
      mammograms. The fate of the capsule around saline implants is less clear. The
      purpose of this study was to determine the fate of the capsule around saline
      filled implants in an animal model. Rats were implanted with 6-ml tissue
      expanders, which were left in place for 4 months. The implants were then removed
      and the capsules around the injection port (smooth surface) and tissue expander
      (textured surface) were examined sequentially. The capsules contracted and
      dissipated gradually over a year in association with a pericapsular vascular
      proliferation. It may not be necessary to perform a capsulectomy at the time of
      saline implant removal.

PMID- 11293510
TI  - Results of immediate breast reconstruction after skin-sparing mastectomy.
AB  - Skin sparing mastectomy (SSM) removes the breast, nipple-areolar complex,
      previous biopsy incisions, and skin overlying superficial tumors. Preservation of
      the native skin envelope facilitates immediate breast reconstruction. The
      procedure has been adopted for the treatment of breast cancer. All cases of SSM
      and immediate breast reconstruction performed by the senior author (G.W.C.) from
      January 1, 1993, through December 12, 1997, were reviewed. Patient demographics,
      cancer staging, treatment, types of surgery performed, and postoperative outcomes
      were examined. Aesthetic outcomes were measured using four 3-point subscales. A
      total of 100 patients underwent 118 SSMs during the study period. The American
      Joint Committee on Cancer staging was as follows: stage 0, 27 patients; stage I,
      25 patients; stage II, 39 patients; stage III, 7 patients; stage IV, 3 patients;
      recurrent, 2 patients; and cystosarcoma phylloides, 1 patient. The mean follow-up
      was 42.7 months. Local recurrence occurred in 2 patients (2.7%). Reconstructive
      methods included the transverse rectus abdominis musculocutaneous flap (N = 82;
      pedicled, 73; free, 9), the latissimus flap (N = 18), and tissue expansion (N =
      20). Two patients underwent contralateral delayed reconstruction. The aesthetic
      results achievable with the three methods were similar. The failure rate was
      higher for expander reconstruction (10%) than those observed for transverse
      rectus abdominis musculocutaneous (4.9%) and latissimus (5.6%) flaps. SSM can be
      used in the treatment of invasive breast cancer without compromising local
      control. The aesthetic results of the three methods were similar, but tissue
      expander reconstruction had a higher failure rate.

PMID- 11293511
TI  - Reconstruction with the latissimus dorsi flap after skin-sparing mastectomy.
AB  - The latissimus dorsi musculocutaneous island flap was once the standard for
      breast reconstruction. With the increased use of tissue expanders and the
      development of the transverse rectus abdominis musculocutaneous flap for
      autologous tissue breast reconstruction, use of the latissimus dorsi has
      decreased. To reassess the role of the latissimus dorsi musculocutaneous flap in
      breast reconstruction, a retrospective review was performed to evaluate women who
      had skin-sparing mastectomy followed by immediate reconstruction with a
      latissimus dorsi flap and permanent implants. The postoperative aesthetic results
      and donor site morbidity, including contour deformity and scarring, were
      examined. Satisfactory results were obtained in 17 of 18 patients. Complications
      were noted in 5 patients, and all were minor. Using the latissimus dorsi
      musculocutaneous flap and a permanent breast prosthesis for immediate
      reconstruction is successful because it provides sufficient muscular coverage of
      the implant. In addition, it provides a good aesthetic result using a single
      stage procedure. Illustrative cases are presented.

PMID- 11293512
TI  - Skin-sparing mastectomy with staged tissue expander reconstruction using a
      silicone gel prosthesis and contralateral endoscopic breast augmentation.
AB  - Women with an A or B cup-size breast with no ptosis or glandular ptosis underwent
      a skin-sparing mastectomy through a periareolar incision. A submuscular tissue
      expander was placed for immediate reconstruction. The periareolar incision was
      closed using a modified pursestring technique. The reconstructed breast was
      expanded to a C cup size. The expander was removed and replaced with a silicone
      gel prosthesis. At the time of tissue expander removal, the contralateral breast
      underwent endoscopic augmentation. Nipple-areolar reconstruction was performed
      during a third stage to cover the mastectomy scar. Implant reconstruction of the
      breast frequently results in a breast mound that has greater upper breast
      fullness than the opposite breast. By augmenting the opposite breast, better
      symmetry is achieved. Burden WR. Skin-sparing mastectomy with staged tissue
      expander reconstruction using a silicone gel prosthesis and contralateral
      endoscopic breast augmentation.

PMID- 11293513
TI  - Endoscopic breast subpectoral augmentation for second-degree breast ptosis.
AB  - Glandular ptosis and first-degree ptosis are treated routinely with breast
      augmentation in select patients. Second-degree ptosis is difficult to treat with
      breast augmentation alone. Patients must be well informed and selected properly
      to obtain a satisfactory result. Historically, second-degree ptosis is treated
      most commonly with subglandular augmentation. The authors demonstrate that second
      degree ptosis may be treated using endoscopic subpectoral augmentation. They
      think that the endoscopic approach gives more control and precision in the
      lowering of the inframammary fold and the placement of the implant. Additionally,
      there may be a decrease or maintenance in the distance from the clavicle to
      nipple because of shortening the pectoralis major as a result of dividing it from
      the sixth rib at the sternal attachment laterally to the serratus fascia.

PMID- 11293514
TI  - Thoracic reconstruction with the omentum: indications, complications, and
      results.
AB  - This study provides a retrospective analysis of 60 patients who underwent
      thoracic reconstruction with the omentum. Patients were identified by searching
      several databases to determine demographics, indications for surgery, operative
      technique, and postoperative course, including donor and recipient site
      morbidity. From January 1975 to May 2000, the authors harvested and transferred
      the omentum successfully (57 pedicled, 3 free) in 60 patients (mean age, 60
      years; age range, 21-86 years) for sternal wound infections (N = 34), chest wall
      resections (N = 17), pectus deformities (N = 2), intrathoracic defects (N = 4),
      and breast reconstruction (N = 3). The omentum was used as a primary flap in 39
      patients and as a salvage flap in 21 patients. Average operative time was 3.9
      hours and average hospital stay was 34.3 days. Partial flap loss occurred in 7
      patients, with no total flap failures. Morbidity included six abdominal wound
      infections and seven epigastric hernias. Mortality was 11.7%. The omentum can be
      harvested safely and used reliably to reconstruct varying thoracic wounds and
      defects. Specific indications from this series include osteoradionecrosis, chest
      wall tumors, massive sternal wounds, and refractory mediastinitis. Hultman CS,
      Culbertson JH, Jones GE, et al. Thoracic reconstruction with the omentum:
      indications, complications, and results.

PMID- 11293515
TI  - The vacuum-assisted closure device as a bridge to sternal wound closure.
AB  - Sixteen patients were treated for sternal wound infections after undergoing
      cardiac procedures. Their management involved prompt surgical debridement and
      quantitative wound biopsies. At the time of the initial debridement, the Vacuum
      Assisted Closure Device (V.A.C.) was placed in the open sternal wound. A
      subatmospheric environment was maintained by the device at a level of 75 to 150
      mmHg. The V.A.C. sponge was changed every 2 to 3 days, and operative debridement
      was performed until quantitative biopsies showed resolution of infection or until
      systemic signs of sepsis had resolved. At this time the sternal wounds were
      closed with regional muscle flaps. Patients were excluded from the use of the
      device if the pleural cavity was entered during operative debridement. Fifteen of
      the 16 patients survived and went on to complete wound healing and discharge from
      the hospital (average length of stay, 16.7 days). One patient sustained a cardiac
      dysrhythmia during the muscle flap procedure and died. There were no
      complications related directly to the use of the V.A.C. It is the opinion of the
      authors that the V.A.C. offers several advantages over their traditional methods
      of treatment. They noted improvement in sternal wound stabilization during the
      perioperative period and a decreased need for paralysis and mechanical
      ventilation. Wound management was improved by avoiding the need to perform
      debridement or to make desiccating dressing changes to an open sternum. Moreover,
      they also think that this device may lessen the risk for ventricular rupture
      because of better control of the wound environment and markedly improved
      stabilization of the debrided sternal elements.

PMID- 11293516
TI  - Microsurgery in private practice: is it feasible economically?
AB  - Microsurgical free tissue transfer and replantations have long been the bailiwick
      of academic training centers and tertiary referral centers. However, the authors'
      experience with more than 350 consecutive free tissue transfers during a span of
      15 years in a purely private setting illustrates the changing economics of the
      medical environment in that time frame. These data provide insight into the
      feasibility and practicality of maintaining a microsurgical practice outside an
      academic medical center.

PMID- 11293517
TI  - Comparison of magnetic resonance angiography and digital subtraction angiography
      for visualization of lower extremity arteries.
AB  - Objective vascular assessment is frequently required before microvascular
      reconstruction involving the lower extremities. The purpose of this study was to
      evaluate the reliability of magnetic resonance angiography (MRA) for preoperative
      assessment before free flap surgery. Five patients underwent preoperative MRA:
      one before fibula harvest for oromandibular reconstruction, and four before
      muscle free flap reconstruction of the lower extremity. In all patients, the
      tibioperoneal trunk, anterior tibial, posterior tibial, and peroneal arteries
      were well visualized to the ankle, including pathological occlusions. The
      radiographic findings were demonstrated at surgery and were confirmed to be
      accurate. These findings facilitated and guided the surgical procedure. This
      study strongly suggests the accuracy and surgical relevance of MRA before free
      flap surgery. MRA is desirable over angiography because of its noninvasive
      nature. It may also be better than ultrasonography because the latter is highly
      dependent on the technician (particularly in identifying the peroneal artery).
      MRA may likely replace angiography as the objective procedure of choice before
      microvascular surgery.

PMID- 11293518
TI  - The nasolabial flap revisited as an adjunct to floor-of-mouth reconstruction.
AB  - Composite free tissue reconstruction for floor-of-mouth defects are thought of as
      single-stage procedures. However, postoperative wound complications often require
      additional soft-tissue coverage to salvage the initial reconstruction. Nasolabial
      flaps interpolated into the oral cavity offer an expedient solution to soft
      tissue deficits encountered during complicated floor-of-mouth reconstructions.
      The records of 39 patients undergoing free tissue reconstruction, from July 1995
      to December 1999 at Shands Hospital and the Gainesville VA Medical Center, for
      floor-of-mouth defects were reviewed. Six patients developed postoperative wound
      complications that compromised the initial reconstruction. In all patients,
      inferiorly based nasolabial flaps were used to provide additional soft-tissue
      coverage and wound closure. Radiation therapy and facial artery ligation did not
      affect the outcome. Complete wound healing and salvage of the initial
      reconstruction was achieved in all 6 patients.

PMID- 11293519
TI  - Analysis of nitric oxide activity in prevention of reperfusion injury.
AB  - This project was designed to determine the role of nitric oxide (NO) in the
      prevention of ischemia-reperfusion injury. Inferiorly based rectus abdominis
      muscle flaps were elevated in pigs and subjected to 6 hours of ischemia followed
      by 4 hours of reperfusion. Group I animals received a bolus of L-arginine before
      reperfusion, and a continuous infusion once flow was restored. Group II animals
      served as controls and received an equal volume of saline as a bolus and
      subsequent continuous infusion. Microdialysis was used to measure tissue NO
      levels, and these were correlated with muscle survival determined by vital
      staining with nitroblue tetrazolium. The results demonstrated a significant
      increase in tissue NO levels in L-arginine-supplemented animals (p < 0.05), which
      in turn correlated with a significant increase in muscle survival (p = 0.0051).
      These results suggest that administration of supplemental L-arginine to ischemic
      skeletal muscle during reperfusion results in increased NO production and
      decreased tissue damage.

PMID- 11293520
TI  - Reconstruction of the submammary crease for correction of postoperative
      deformities in aesthetic and reconstructive breast surgery.
AB  - This article discusses a method of reconstruction of breast crease for correction
      of postoperative deformities. These deformities are usually the result of implant
      insertion for the purpose of breast enlargement or reconstruction. The operation
      is performed by creating a new crease in the appropriate site by suturing
      capsular and soft tissue structures from the anterior to the posterior wall of
      the pocket to eliminate excess space at the lower, medial, or lateral breast.
      This article will detail crease reconstruction through an internal approach.
      Patient selection, technique, and results are discussed.

PMID- 11293521
TI  - Offspring health risk after cosmetic breast implantation in Sweden.
AB  - Case reports have suggested that children born to women with silicone breast
      implants may have an excess risk of rheumatic disease and/or esophageal
      disorders. In Sweden, the authors conducted a retrospective cohort study of 5,874
      children born to women with cosmetic breast implants and 13,274 children born to
      women who had breast reduction surgery. Using national registers, they computed
      hospitalization rates for rheumatic and esophageal disorders, incidence rates for
      cancer, and prevalence rates for congenital malformations and perinatal death.
      Relative to children of women who had breast reduction surgery, children born to
      women who had cosmetic breast implants were not at excess risk of rheumatic
      disease (relative risk [RR] = 1.1; 95% confidence interval [95% CI], 0.2-5.3),
      esophageal disorders (RR = 1.0; 95% CI, 0.7-1.6), cancer (RR = 0.3; 95% CI, 0.0
      2.5), congenital malformations in total (RR = 1.0; 95% CI, 0.6-1.5), or
      specifically involving the digestive organs (RR = 0.5; 95% CI, 0.2-1.3) or
      perinatal death (RR = 0.9; 95% CI, 0.5-1.8). The rates of these health outcomes
      among children born after a mother's implant surgery were also not significantly
      higher than among children born before a mother's implant surgery. This study
      provides no evidence that certain hypothesized health outcomes are more likely
      among the children of women with cosmetic breast implants.

PMID- 11293523
TI  - Guidelines for standard photography in plastic surgery.
AB  - Uniform patient photographs that create permanent records are essential for any
      visually oriented medical specialty. These images are valuable for any plastic
      surgeon's practice for various reasons; thus, standards and recommendations for
      clinical photography should be well-known. There are several articles published
      on this issue, but it is still not uncommon to be exposed to medical publications
      and presentations that fail to satisfy clinical photography standards. This
      stimulated an interest in reviewing the important factors that are essential to
      achieve consistent, comparable clinical photographs with 35-mm single-lens reflex
      photography.

PMID- 11293522
TI  - Clinical and histopathological analysis of tissue retraction in tumescent
      liposuction assisted by external ultrasound.
AB  - Multiple subjective evaluations and valuations in clinical studies have suggested
      that the use of external ultrasound in liposuction favors the degree of tissue
      retraction. However, studies do not exist that evaluate with objective parameters
      the degree of tissue retraction after liposuction assisted with external
      ultrasound. It is for this reason that a comparative clinical trial was carried
      out in 13 female patients to establish clinically and histopathologically the
      degree of tissue retraction that is produced after tumescent liposuction assisted
      by external ultrasound compared with the classic tumescent technique. All
      patients were tattooed in each hemiabdomen with reference points that formed a 7
      x 7-cm square. Abdominal tumescent liposuction was carried out in all patients,
      with external ultrasound applied to the right hemiabdomen only, and without
      specifying to the patient the side on which the ultrasound was applied. The areas
      were measured and biopsies were acquired in each hemiabdomen 72 hours, 1 week, 2
      weeks, 3 months, and 6 months postoperatively. The samples were evaluated by the
      same pathologist in a double-blind study. A survey of the patients was carried
      out regarding their appreciation of the results at the end of 3 months. On
      physical evaluation of the tattooed square, none of the thirteen patients
      presented significant differences in skin retraction (95% dependability by means
      of Student's t-test). The histological results showed that external ultrasound
      increased the degree of edema, vascular congestion, and inflammatory infiltration
      in the dermis during the first 3 months postoperatively. However, after 6 months
      no differences existed. Clinically, no patient observed a marked difference
      between the two hemiabdominal areas; an equal aesthetic result was obtained on
      both sides. In this clinical comparative trial, external ultrasound as a
      complementary method to tumescent liposuction did not increase the degree of
      tissue retraction after the liposuction, nor did it prove to be a determining
      factor in the immediate postoperative evolution.

PMID- 11293524
TI  - Cross-facial nerve grafting as an adjunct to hypoglossal-facial nerve crossover
      in reanimation of early facial paralysis: clinical and electrophysiological
      evaluation.
AB  - Reanimation of a spontaneous and synchronous smile, and sufficient depressor
      mechanism of the lower lip presents a surgical challenge in facial paralysis.
      Hypoglossal-facial nerve crossover and cross-facial nerve grafting are the best
      options if the mimetic muscles around the mouth are still viable in patients in
      whom the facial nerve was sacrificed at the brainstem. Although good muscle tone
      and facial motion have been obtained by hypoglossal-facial nerve crossover, smile
      is dependent on conscious tongue movement. Cross-facial nerve grafting provides a
      voluntary and emotion-driven smile, but requires two coaptation sites, which
      leads to substantial axonal loss and a long regeneration time. This method was
      not successful in activating the depressor mechanism. The first stage is the
      classic "baby-sitting" procedure, in which the bulk of the mimetic muscles was
      maintained by the rapid reinnervation of the hypoglossal-facial nerve crossover
      during the regeneration period of the cross-facial nerve graft, and temporalis
      muscle transfer to the eyelids is performed. During the second stage, the cross
      facial nerve graft that used the thickest zygomaticobuccal branch on the healthy
      side was coapted with the corresponding branches on the paralyzed side. The
      hypoglossal-facial nerve crossover continued to innervate the depressor muscles.
      Good spontaneous smile and sufficient depressor mechanism were achieved by cross
      facial nerve grafting and hypoglossal-facial nerve crossover respectively, and
      these techniques are demonstrated by the authors clinically and
      electrophysiologically.

PMID- 11293525
TI  - The distally based island superficial sural artery flap: clinical experience with
      36 flaps.
AB  - The principles of neurocutaneous flaps, first described by Masquelet in 1992,
      represented a new concept in skin vascularization. The distally based superficial
      sural artery flap is an example of this kind of flap, which is supplied by the
      vascular axis that accompanies the sural nerve. The authors treated 36 patients
      with 36 distally based superficial sural artery flaps. All flaps survived, but
      six of them exhibited partial necrosis. No patient experienced anesthesia of the
      lateral side of the foot or neuroma at the donor site 12 months after surgery.
      The authors confirmed that this flap is very useful for soft-tissue
      reconstruction of the distal third of the leg and foot. Additionally they
      conclude that the principal advantages are that the blood supply is reliable,
      execution is easy and fast, the operation can be performed under regional
      anesthesia, the flap has a large arc of rotation, direct closure of the donor
      area is possible for small flaps, major arteries or nerves are not sacrificed,
      and excellent durability is achieved, even on weight-bearing areas. The major
      drawback is the donor site scar.

PMID- 11293526
TI  - Improvement of skin paddle survival by  application of vascular endothelial
      growth factor in a rat TRAM flap model.
AB  - The effect of vascular endothelial growth factor (VEGF) on skin flap survival and
      its ability to induce a pharmacological delay by promoting angiogenesis in a flap
      was studied in a rat transverse rectus abdominis musculocutaneous flap, using a 3
      x 8-cm skin paddle with the inferior epigastric vessels as its main vascular
      supply. Forty-three Sprague-Dawley rats were divided into four groups. In group
      1, VEGF was injected into the femoral vein after the flap was elevated. In group
      2, VEGF was injected intra-arterially into the flap through the superior
      epigastric artery after the flap was elevated. In group 3, VEGF was injected into
      the subcutaneous fascial layer in the area where the flap would be dissected, and
      the flap was then raised 7 days after injection. In group 4, the flap was
      dissected and replaced, using saline injection as the control. On postoperative
      day 5, the survival area of each skin paddle was measured and the flap was
      harvested for histological analysis. The results showed that the mean survival
      area +/- standard deviation for the skin paddle was 6.82 +/- 4.89 cm2 (28.4 +/-
      20.4% of the whole skin paddle) in the control group, and 4.2 +/- 3.0 cm2 (17.5
      +/- 12.5%) and 6.02 +/- 5.97 cm2 (25.1 +/- 24.9%) in the groups with VEGF
      systemic and intra-arterial administration respectively. The skin survival area
      in the group with preoperative subcutaneous administration of VEGF was 17.85 +/-
      2.88 cm2 (74.4 +/- 12%), which was significantly higher than the other three
      groups (p < 0.01). Histological semiquantitative analysis showed increased
      neovascularization in the flap treated with VEGF preoperatively. The data
      demonstrate that preoperative treatment with VEGF can induce angiogenesis and
      enhance skin paddle survival in a musculocutaneous flap.

PMID- 11293527
TI  - Pretreatment with glycine reduces the severity of warm intestinal ischemic
      reperfusion injury in the rat.
AB  - Free jejunal flaps may experience adverse effects immediately after
      revascularization because of ischemic-reperfusion injury. In this study the
      authors evaluated the ability of glycine to protect the small intestine against
      the effects of a warm ischemic-reperfusion injury. Male Wistar rats (N = 30) were
      randomized to either a baseline group (no intervention), a control group (local
      arterial infusion with normal saline), or a glycine group (local arterial
      infusion with 20% glycine). Pretreatment with 20% glycine increased significantly
      (p < 0.05) mucosal protein and deoxyribonucleic acid content, reduced intestinal
      myeloperoxidase activity, and maintained mucosal glutaminase activity. These
      results indicate that some of the indicators of ischemic-reperfusion injury are
      improved by pretreatment with a 20% glycine solution.

PMID- 11293528
TI  - An anatomic comparison of the skin of five donor sites for dermal fat graft.
AB  - Kim performed more than 3,000 augmentation rhinoplasties using the dermal fat
      graft. He preferred the sacral area as the donor site over other areas because
      the dermis is thick and the fat is more compact. The authors conducted a
      comparative study of the thickness of the epidermis and dermis, and the numbers
      of fibroblasts and fibrocytes in the dermis of the abdominal wall, groin, lateral
      gluteal area, gluteal fold, and sacrum of 7 adult cadavers. The sacrum had the
      thickest epidermis (86.1 +/- 7.8 microm) and dermis (1,510.7 +/- 201.7 microm),
      and the groin had the thinnest epidermis (57.3 +/- 22.9 microm) and dermis (783.3
      +/- 244.5 microm). The dermal thickness of the abdomen, lateral gluteal area, and
      gluteal fold was 913.3 +/- 271.7 microm, 1,018.7 +/- 305.6 microm, and 1,107.0 +/
      272.6 microm respectively. The sacral dermis was significantly thicker than the
      other four sites (p < 0.008), and the groin dermis was the thinnest (p < 0.039).
      The number of fibroblasts and fibrocytes in the sacral area and the gluteal skin
      folds was significantly higher than the other areas (p < 0.05). The sacral area,
      gluteal fold, and lateral gluteal region had relatively thicker panniculus
      adiposus than the abdomen and groin. The panniculus adiposus of the sacral skin
      was especially well developed and was comprised of several compact layers that
      were connected by parallel, thick collagen fibers. The authors conclude that the
      sacral skin is a suitable donor site for dermal grafting because its dermis has
      more fibroblasts and fibrocytes than the other areas studied, and its dermis is
      more viable and durable.

PMID- 11293529
TI  - Treatment of facial angiofibromas of tuberous sclerosis by shave excision and
      dermabrasion in a dark-skinned patient.
AB  - Tuberous sclerosis is an inherited disease expressed clinically by the triad of
      mental retardation, seizures, and tuberous lesions. Facial angiofibromas, a
      common manifestation of tuberous sclerosis, can cause considerable cosmetic
      disfigurement, emotional distress, obstruction of vision, and hemorrhage.
      Treatment by shave excision, as the first step to remove the larger nodules,
      followed by dermabrasion, to smooth and sculpt the final surface, has been
      recommended as the most effective form of therapy. However, this method of
      treatment raises the question of risk for development of hypopigmentation in
      susceptible patients. The authors present their treatment of angiofibromas with
      shave excision and dermabrasion in a dark-skinned patient.

PMID- 11293530
TI  - Multiple-component tissue reconstruction of a complex dorsal foot wound through a
      single gracilis muscle donor incision.
AB  - The authors describe the ability of the gracilis muscle to provide multiple
      tissue components- skin, muscle, nerve, and tendonin the reconstruction of a
      complex dorsal foot wound resulting from a sarcoma resection. The deficits of
      skin, deep peroneal nerve, anterior tibialis tendon, and dorsal extensor
      retinaculum were all reconstructed with the gracilis component flap through one
      medial thigh incision. This case illustrates two important points: (1) the
      gracilis flap is tremendously versatile and can serve as the donor for multiple
      tissue components in complex reconstructions, and (2) donor site morbidity can
      and should be minimized even in complex reconstructions.

PMID- 11293531
TI  - The W-W-Z rhomboid plasty for closure of excisional wounds.
AB  - A new method of repairing excisional wounds in the face, trunk, and extremities
      is demonstrated. The rhomboid W-W-Z-plasty approach is an evolution of the double
      Z rhomboid plasty already published. The authors have recognized its value in
      covering even large defects. The W-W-Z rhomboid plasty adds new gains to the
      repair of excisional wounds such as skin-sparing resection, fewer scars, less
      deformity, and a desirable resulting z-shaped scar. The surgical technique and an
      illustrative case are described.

PMID- 11293532
TI  - A tangled web.

PMID- 11293533
TI  - Re: Hypospadias repair: collaboration between urologist and plastic surgeon.

PMID- 11293534
TI  - Re: Total reconstruction of the alar cartilages with a partially split septal
      cartilage graft.

PMID- 11293535
TI  - Re: A modified reversed digital island flap incorporating the proper digital
      nerve.

PMID- 11293536
TI  - Potential for danger with Arnica montana.

PMID- 11293537
TI  - False median cleft: a rare facial anomaly.

PMID- 11293538
TI  - Type I first branchial cleft anomaly resembling an epidermal cyst.

PMID- 11293539
TI  - A case with accessory digastric muscles and its clinical importance.

PMID- 11293540
TI  - A-3 pulley trigger finger.

PMID- 11293541
TI  - An infiltrating intramuscular lipoma of the brachioradialis muscle.

PMID- 11293542
TI  - Other uses of AlloDerm: case reports.

PMID- 11293543
TI  - Heme-Cu complexes as oxygen-activating functional models for the active site of
      cytochrome c oxidase.
AB  - Tri(2-pyridylmethyl)amineCu complex-linked iron meso-tetraphenylporphyine
      derivatives were prepared to model the active site of cytochrome c oxidase.
      Exposure to oxygen converted the reduced forms of the complexes to the
      corresponding stable mu-peroxo species in spite of the presence of three
      coordination sites, two on the heme and one on the Cu. The oxy forms were
      characterized spectroscopically. Kinetic analyses of the oxygenation reactions of
      the reduced forms suggests that preferential O2 binding occurs at the Cu site
      over the heme. This mechanism is also supported by examination of the redox
      potentials of the two metal ions. Since the peroxy complexes of the models
      exhibit a structure similar to that of the previously reported fully-oxidized
      form, the relevance of the model chemistry to the enzyme reaction is discussed.

PMID- 11293544
TI  - Fe-type nitrile hydratase.
AB  - The characteristic features of Fe-type nitrile hydratase (NHase) from Rhodococcus
      sp. N-771 are described. Through the biochemical analyses, we have found that
      nitric oxide (NO) regulates the photoreactivity of this enzyme by association
      with the non-heme iron center and photoinduced dissociation from it. The
      regulation is realized by a unique structure of the catalytic non-heme iron
      center composed of post-translationally modified cysteine-sulfinic (Cys-SO2H) and
      -sulfenic acids (Cys-SOH). To understand the biogenic mechanism and the
      functional role of these modifications, we constructed an over-expression system
      of whole NHase and individual subunits in Escherichia coli. The results of the
      studies on several recombinant NHases have shown that the Cys-SO2H oxidation of
      alphaC112 is indispensable for the catalytic activity of Fe-type NHase.

PMID- 11293545
TI  - Putidaredoxin-cytochrome P450cam interaction.
AB  - Cytochrome P450cam (P450cam) catalyzes the monooxygenation of D-camphor. During
      the enzymatic reaction, oxyferrous, D-camphor-bound P450cam forms a binary
      complex with reduced putidaredoxin as an obligatory reaction intermediate. We
      have found that reduced putidaredoxin undergoes EPR-detectable conformational
      changes upon formation of the intermediate complex and also upon formation of a
      binary complex with CO- or NO-ferrous, D-camphor-bound P450cam. The structural
      changes in putidaredoxin are almost identical irrespective of the ligand bound to
      P450cam, and distinct from and significantly larger than those induced by
      unliganded ferrous P450cam. The binary complex formation also induce
      conformational alterations in the CO- and NO-ferrous, D-camphor-bound P450cam,
      thereby evoking simultaneous changes in the structure of the two proteins. A
      molecular basis and roles of such structural changes in the D-camphor
      monooxygenation are discussed.

PMID- 11293546
TI  - Effect of microsome-liposome fusion on the rotational mobility of cytochrome
      P450IIB4 in rabbit liver microsomes.
AB  - Membrane fusion of microsomes with soybean phospholipid vesicles was performed at
      pH 6.5 to investigate the effect of lipid-enrichment in the membrane on the
      rotational mobility of cytochrome P450. Rotational diffusion of cytochrome P450
      in the microsomal membrane of phenobarbital-induced rabbit liver was measured by
      detecting the decay of absorption anisotropy after photolysis of the heme CO
      complex by a vertically polarized laser flash. The fusion procedures yielded
      three separate fractions upon sucrose density gradient centrifugation with lipid
      to-protein ratio in weight (L/P) as follows: 1.5 in the bottom fraction, 2.2 in
      the middle fraction, and 3.9 in the top fraction. In each fraction, co-existence
      of mobile and immobile cytochrome P450 was observed. The percentage of
      rotationally mobile P450 (with the mean rotational relaxation time of phi=505-828
      micros) in each of the different bands was found to be 59% in the bottom
      fraction, 61% in the middle fraction, and 68% in the top fraction. This increase
      in mobile population of P450 due to lipid-enrichment indicates that aggregated
      proteins in microsomal membranes dissociate with increasing L/P which is
      inversely proportional to the protein concentration in the membrane. With freeze
      fracture electron microscopy, it was shown that the average distance increased
      between intramembrane particles by lipid-enrichment. Thus, the significant
      immobile population (32%) of P450 in microsomal membranes can be explained by
      nonspecific protein aggregation which is a consequence of the low L/P of 0.8. The
      decrease in the mobile population in the bottom fraction compared with intact
      microsomes was shown to be due to the pH 6.5 incubation used for fusion.

PMID- 11293547
TI  - Crystal structures of substrate free and complex forms of reactivated BphC, an
      extradiol type ring-cleavage dioxygenase.
AB  - BphC derived from Pseudomonas sp. strain KKS102, an extradiol type catecholic
      dioxygenase, is a non-heam iron-containing enzyme, playing an important role in
      the degradation of biphenyl/PCB (Poly Chlorinated Biphenyls) in the microbe.
      Although we had earlier solved the crystal structure of KKS102 BphC, it was the
      inactive form with Fe(III) in the active site. In order to determine the active
      form structure, BphC was re-activated by anaerobic incubation with Fe(II) and
      ascorbate, and crystallized anaerobically. The crystal structures of activated
      BphC and its substrate complex (E x S complex) were determined at 2.0 A
      resolution under cryogenic condition. In addition, crystal structures of
      unactivated BphC in substrate free and complex forms were also re-determined.
      Comparison of activated and unactivated E x S complexes reveals that the
      orientation of the bound substrate in the active site is significantly different
      between the two. The structural comparison of the substrate free and complex
      forms of activated BphC show certain small conformational shifts around the
      active site upon substrate binding. As a result of the conformational shifts,
      His194, which has been suggested as the catalytic base, takes part in a weak
      hydrogen bond with hydroxyl group of the substrate.

PMID- 11293548
TI  - Perturbations at the high spin heme b center in the membrane-bound nitric oxide
      reductase.
AB  - The effects of lowering pH from 7 to 5 on the absorption, circular dichroism
      (MCD) and EPR spectra were studied for Paracoccus halodenitrificans nitric oxide
      reductase (NOR). Intensities of the characteristic bands for the high spin heme
      b, that at 592 nm in the absorption spectrum and those at 591 (+) and 606 (-) in
      the MCD spectrum decreased considerably. Concomitant cryogenic EPR spectrum
      indicated a drastic increase in the signal intensity due to the high spin heme b
      at g approximately 6, of which less than 5% had been EPR detectable at pH 7.
      Cyanide (x40) bound to the high spin heme b center in the reduced NOR
      irrespective of pH, while a much larger amount of azide (x1000) was necessary to
      bind to the reduced NOR at an acidic pH, ca. 5. Based on these results the
      structure and function of the high spin heme b center as the active site of NOR
      was discussed.

PMID- 11293549
TI  - Synthetic active site analogues of heme-thiolate proteins. Characterization and
      identification of intermediates of the catalytic cycles of cytochrome P450cam and
      chloroperoxidase.
AB  - In view of recent results from different sources, the reaction mechanisms of two
      heme-thiolate proteins, cytochrome P450cam and chloroperoxidase (CPO), are
      discussed. In this context a mechanism of CPO is proposed which includes H2O2
      cleavage, subsequent formation of compound I and the identification of two
      elusive intermediates. The HOCl adduct of the iron(III)porpyhrin is the
      catalytically competent Cl+ donor chlorinating activated C-H bonds of substrates
      bound to the enzyme. Pulse-EPR characterization of an enzyme model of the resting
      state of P450cam suggests a role of the electric field of the protein for
      stabilizing the low-spin state of the cofactor of the enzyme. It is further
      suggested that the same effect of the protein may trigger the reactivity of
      compound I such that both concerted and two-step reactions are feasible within
      the concept of a Two-State-Reactivity. This review emphasizes the value of
      synthetic enzyme models complementing investigations of the native proteins.

PMID- 11293550
TI  - A proximal tryptophan in NO synthase controls activity by a novel mechanism.
AB  - The heme of neuronal nitric oxide synthase (nNOS) participates in O2 activation
      but also binds self-generated NO, resulting in reversible feedback inhibition. We
      utilized mutagenesis to investigate if a conserved tryptophan residue (Trp409),
      which engages in pi-stacking with the heme and hydrogen bonds to its axial
      cysteine ligand, helps control catalysis and regulation by NO. Mutants W409F and
      W409Y were hyperactive regarding NO synthesis without affecting cytochrome c
      reduction, reductase-independent N-hydroxyarginine oxidation, or Arg and
      tetrahydrobiopterin binding. In the absence of Arg electron flux through the heme
      was slower in the W409 mutants than in wild-type. However, less NO complex
      accumulated during NO synthesis by the mutants. To understand the mechanism, we
      compared the kinetics of heme-NO complex formation, rate of heme reduction, kcat
      prior to and after NO complex formation, NO binding affinity, NO complex
      stability, and its reaction with O2. During the initial phase of NO synthesis,
      heme-NO complex formation was three and five times slower in W409F and W409Y,
      which corresponded to a slower heme reduction. NO complex formation inhibited
      wild-type turnover 7-fold but reduced mutant turnover less than 2-fold, giving
      mutants higher steady-state activities. NO binding kinetics were similar among
      mutants and wild type, although mutants also formed a 417 nm ferrous-NO complex.
      Oxidation of ferrous-NO complex was seven times faster in mutants than in wild
      type. We conclude that mutant hyperactivity primarily derives from slower heme
      reduction and faster oxidation of the heme-NO complex by O2. In this way Trp409
      mutations minimize NO feedback inhibition by limiting buildup of the ferrous-NO
      complex during the steady state. Conservation of W409 among NOS suggests that
      this proximal Trp may regulate NO feedback inhibition and is important for enzyme
      physiologic function.

PMID- 11293551
TI  - Calculation of the electronic structure and spectra of model cytochrome P450
      compound I.
AB  - The electronic structure and spectra of the oxyferryl (Fe=O) compound I P450 heme
      species, the transient putative active intermediate of cytochrome P450s, have
      been calculated employing a full protoporphyrin IX heme model representation. The
      principal aim of this work was to compare the computed spectra of this species
      with the observed transient spectra attributed to it. Computations were made
      using both nonlocal density functional theory (DFT) and semiempirical INDO/CI
      methods to characterize the electronic structure of the compound I P450 species.
      Both methods resulted in a similar antiferromagnetic doublet as the ground state
      with a ferromagnetic quartet excited state partner, slightly higher in energy.
      The INDO/ROHF/CI semiempirical method was used to calculate the spectrum of the
      protoporphyrin IX P450 compound I heme species in its lowest energy
      antiferromagnetic doublet state at the DFT optimized geometry. As a reference,
      the spectrum of the ferric resting form of the protoporphyrin IX P450 heme
      species was also calculated. The computed shifts in the Soret and Q bands of
      compound I relative to the resting state were both in good agreement with the
      corresponding experimentally observed shifts in the transient spectra of
      cytochrome P450cam (Biochem. Biophys. Res. Commun. 201 (1994) 1464) and
      chloroperoxidase (Biochem. Biophys. Res. Commun. 94 (1980) 1123) both ascribed to
      their common compound I heme site. This consistency provides additional,
      independent support for the assignment of compound I as the origin of the
      reported observed transient spectra.

PMID- 11293552
TI  - Efficacy and tolerability of fluvastatin extended-release delivery system: a
      pooled analysis.
AB  - BACKGROUND: At high doses, the pharmacokinetics of fluvastatin immediate-release
      (IR) are nonlinear, possibly due to saturation of hepatic uptake. Fluvastatin
      delivery to the liver in a slower but sustained fashion would be expected to
      avoid hepatic saturation without elevating systemic drug levels. OBJECTIVE: This
      pooled analysis compared the efficacy and tolerability of extended-release (XL)
      80-mg and IR 40-mg formulations of fluvastatin in lowering low-density
      lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and raising high
      density lipoprotein cholesterol (HDL-C) levels in patients with
      hypercholesterolemia. METHODS: Data were pooled from 3 double-blind, randomized,
      active-controlled, multicenter, parallel-group studies that compared changes in
      lipid and apolipoprotein levels with fluvastatin XL 80 mg at bedtime (HS) with
      changes in fluvastatin IR 40 mg HS or BID in patients aged > or =18 years with
      primary hypercholesterolemia (consistently elevated LDL-C level [> or =160 mg/dL]
      and plasma TG levels < or =400 mg/dL). The primary efficacy variable was percent
      change in LDL-C from baseline. RESULTS: The pooled analysis provided an intent-to
      treat efficacy study population of 1674 patients. At 4 weeks, fluvastatin XL 80
      mg HS reduced LDL-C levels by a mean of 36.3% (median 38%), significantly greater
      than a mean reduction of 25.9% (median 27%) seen with fluvastatin IR 40 mg HS,
      and an incremental additional mean reduction in LDL-C of 10.4% (P < 0.001). At 4
      and 24 weeks, fluvastatin XL 80 mg HS provided an LDL-C reduction equivalent to
      fluvastatin IR 40 mg BID (P < 0.001 for noninferiority). Significant, dose
      related changes in HDL-C, LDL-C:HDL-C ratio, total cholesterol, TG, and
      apolipoprotein A-I and apolipoprotein B levels also occurred. Mean HDL-C level
      increased by 8.7% and median TG level decreased by 19% with fluvastatin XL 80 mg
      HS (P < 0.001 and P < 0.05 vs fluvastatin IR 40 mg HS, respectively). Maximum
      mean increases in HDL-C level (21%) and median decreases in TG level (31%) with
      fluvastatin XL 80 mg HS occurred in patients with type IIb dyslipidemia and the
      highest baseline TG. Adverse events were mild, with similar frequency in all
      treatment groups. CONCLUSIONS: Once-daily administration of fluvastatin XL 80 mg
      provides enhanced efficacy with an additional 10.4% reduction in LDL-C levels
      compared with fluvastatin IR 40 mg HS, and superior increases in HDL-C levels,
      particularly in patients with elevated TG levels (P < 0.05 vs fluvastatin IR 40
      mg HS). Fluvastatin XL 80 mg HS has a good tolerability profile and is effective
      as starting and maintenance lipid-lowering treatment in patients with type II
      hypercholesterolemia.

PMID- 11293553
TI  - Cefprozil versus high-dose amoxicillin/clavulanate in children with acute otitis
      media.
AB  - BACKGROUND: The recommendation of the Drug-Resistant Streptococcus pneumoniae
      Therapeutic Working Group that high-dose amoxicillin, with or without
      clavulanate, be used to treat acute otitis media (AOM) addressed concerns about
      the efficacy of existing therapies against drug-resistant S. pneumoniae. This
      recommendation relied on pharmacodynamic predictions of concentrations of
      amoxicillin in middle-ear fluid remaining higher than minimum inhibitory
      concentrations against intermediately resistant S. pneumoniae for >40% of the
      dosing interval. OBJECTIVE: This study compared the tolerability and efficacy of
      cefprozil and high-dose amoxicillin/clavulanate in patients with AOM. METHODS:
      Patients were randomized to receive 10 days of investigator-blinded oral
      treatment with either cefprozil suspension (30 mg/kg/d in 2 divided doses) or
      amoxicillin/clavulanate (45/6.4 mg/kg/d) plus amoxicillin (45 mg/kg/d) in 2
      divided doses. The primary efficacy end point was the clinical cure rate 4 to 7
      days after the end of treatment. Clinical response by age (6 months-<2 years vs >
      or =2-7 years), disease severity, and unilateral versus bilateral ear infection
      was also examined. The primary measures of tolerability were the frequency and
      severity of adverse events and their relation to study drug. Adverse events were
      either spontaneously reported or elicited during examination and questioning of
      the patient. Identified adverse events were coded and recorded using the COSTART
      (Coding Symbols for Thesaurus of Adverse Reaction Terms) system. RESULTS: Three
      hundred four children between the ages of 6 months and 7 years with > or =1 sign
      or symptom of AOM were enrolled in the study, and 303 (150 cefprozil, 153
      amoxicillin/clavulanate) were treated. Twenty-three patients in each treatment
      group were not evaluable; thus, 257 children were included in the analysis of
      evaluable patients. Clinical cure rates were 87% (110/127) with cefprozil and 89%
      (116/130) with amoxicillin/clavulanate (95% CI for the difference in cure rate, 
      10.7% to 4.1%). No between-group differences in efficacy were noted by age,
      disease severity, or unilateral or bilateral involvement. The overall incidence
      of drug-related adverse events was significantly lower with cefprozil than with
      amoxicillin/clavulanate (19% vs 32%, respectively; P = 0.008), as was the
      incidence of diarrhea (9% vs 19%, respectively; P = 0.021). Adverse events
      prompted discontinuation of therapy in 4 (3%) cefprozil patients and 8 (5%)
      amoxicillin/clavulanate patients. CONCLUSIONS: Based on a search of MEDLINE, this
      study is the first direct comparison of cefprozil versus high-dose
      amoxicillin/clavulanate. Cefprozil was as effective as high-dose
      amoxicillin/clavulanate, with a lower incidence of adverse events.

PMID- 11293554
TI  - Comparison of the cumulative irritation potential of adapalene gel and cream with
      that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin
      gel.
AB  - BACKGROUND: Adapalene is a naphthoic acid derivative with retinoid activity that
      is effective in the treatment of mild to moderate acne vulgaris. OBJECTIVE: This
      study assessed the cumulative irritation potential of adapalene gel (0.1%) and
      adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%)
      solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin
      (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). METHODS:
      This was a single-center, randomized, controlled, investigator-blinded,
      intraindividual comparison study in healthy subjects with normal skin. The
      cumulative irritation assay (patch test) was used to assess the potential for
      irritation (including erythema) of the treatments. Each subject received all
      study treatments, randomly applied under occlusion (patch), to sites on either
      side of the midline on the mid-thoracic area of the back. All patches were
      applied to the same sites throughout the study, unless the degree of reaction to
      the treatment or adhesive necessitated removal. For 3 weeks, each test material
      was applied daily, Monday through Friday, for approximately 24 hours; the Friday
      patches were left in place over the weekend for approximately 72 hours. RESULTS:
      All 36 subjects (26 men, 10 women; age, 18-49 years [mean, 30 years]) completed
      the study. In the course of the study, all subjects had > or =1 application
      discontinued prematurely on > or =1 site due to intolerance. There were no
      discontinuations with white petrolatum. All erythromycin/tretinoin gel patches
      were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were
      discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were
      discontinued at day 11 or day 17. The adapalene products, although slightly more
      irritating (mean cumulative irritation index, 0.25-1) than white petrolatum, were
      significantly less irritating than the erythromycin/tretinoin and
      erythromycin/isotretinoin products (P < 0.01). CONCLUSIONS: Adapalene gel and
      cream were well tolerated, with possible benefits for compliance. Their low
      irritation potential should be considered when prescribing a topical retinoid for
      the treatment of acne vulgaris.

PMID- 11293555
TI  - Comparison of once-daily and twice-daily administration of celecoxib for the
      treatment of osteoarthritis of the knee.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability
      of a celecoxib 200 mg QD regimen with a 100 mg BID regimen in patients with
      osteoarthritis (OA) of the knee. METHODS: Patients enrolled in this prospective,
      double-blind, placebo-controlled, parallel-group, multicenter study were randomly
      assigned to receive celecoxib 100 mg BID, celecoxib 200 mg QD, or placebo for 6
      weeks. Assessments of OA severity (Patient's and Physician's Global Assessments
      of Arthritis, Patient's Assessment of Arthritis Pain-Visual Analog Scale,
      Lequesne Osteoarthritis Severity Index, and the Western Ontario and McMaster
      Universities Osteoarthritis Index) were performed at baseline and at week 2
      and/or 6. Patients who discontinued treatment underwent assessments at the time
      of withdrawal from the study. RESULTS: Of the 718 patients enrolled, 243 received
      celecoxib 100 mg BID, 231 received celecoxib 200 mg QD, and 244 received placebo.
      For all measures of efficacy, at all assessments, improvements from baseline in
      both celecoxib groups were superior to that seen in the placebo group (P < 0.05).
      No significant differences in efficacy between the celecoxib groups were
      observed. The overall incidence of adverse events was similar in the 2 celecoxib
      treatment groups. CONCLUSIONS: Dosing regimens of celecoxib 200 mg QD and 100 mg
      BID are equally effective and well tolerated in patients with OA of the knee. The
      availability of 2 effective regimens provides patients and physicians with
      increased flexibility in the selection of an appropriate dosing regimen for
      celecoxib therapy.

PMID- 11293556
TI  - Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the
      treatment of pain after ambulatory orthopedic surgery in adults.
AB  - BACKGROUND: Current outpatient management of postoperative pain includes the use
      of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, both
      types of medications are associated with side effects that can limit their
      usefulness in the outpatient setting. OBJECTIVE: Two studies with identical
      protocols assessed the single- and multiple-dose analgesic efficacy and
      tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the
      treatment of acute pain after orthopedic surgery. METHODS: These were
      multicenter, randomized, placebo- and active-controlled, double-blind, parallel
      group trials conducted between January and June 1998. Both consisted of a single
      dose assessment period (SDAP) and a multiple-dose assessment period (MDAP). In
      the SDAP, patients who had undergone orthopedic surgery received a single oral
      dose of celecoxib 200 mg, hydrocodone 10 mg/acetaminophen 1000 mg, or placebo
      within 24 hours after the end of anesthesia, with pain assessments conducted over
      the following 8-hour period. In the MDAP, extending from 8 hours after the first
      dose of study medication up to 5 days, patients who had received < or =1 dose of
      rescue medication during the SDAP continued on study medication (placebo
      recipients were rerandomized to active treatment), which could be taken up to 3
      times a day as needed. RESULTS: A total of 418 patients were enrolled in the 2
      trials. During the SDAP, 141 patients received celecoxib, 136 received
      hydrocodone/acetaminophen, and 141 received placebo. During the MDAP, 185
      patients received celecoxib and 181 received hydrocodone/acetaminophen. When the
      combined data were analyzed, mean pain intensity difference (PID) scores
      generally favored the active treatments over placebo from 1 to 6 hours (with the
      exception of 1.5 hours) after dosing (P < or = 0.016) and favored celecoxib over
      the other treatments at 7 and 8 hours after dosing (P < 0.001). The active
      treatments demonstrated superior summed PID scores through 8 hours (P < 0.001),
      significantly shorter median times to onset of analgesia (P < 0.05), and
      significantly longer median times to first use of rescue medication (P < 0.05).
      During the MDAP, more hydrocodone/acetaminophen-treated patients (20%) than
      celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the
      celecoxib group had significantly lower maximum pain intensity scores (P < 0.001,
      days 2-5), required fewer doses of study medication (P < or = 0.01, days 3-5),
      and had superior scores on a modified American Pain Society Patient Outcome
      Questionnaire (P < or = 0.013). In addition, a significantly lower proportion of
      celecoxib-treated patients experienced adverse events (43%) compared with
      hydrocodone/acetaminophen-treated patients (89%; P < 0.001). CONCLUSIONS: Over 8
      hours, patients with moderate to severe pain after orthopedic surgery experienced
      comparable analgesia with single doses of celecoxib and
      hydrocodone/acetaminophen. Over a 5-day period, oral doses of celecoxib 200 mg
      taken 3 times a day demonstrated superior analgesia and tolerability compared
      with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day. Most patients
      required no more than 2 daily doses of celecoxib 200 mg for the control of their
      postorthopedic surgical pain.

PMID- 11293557
TI  - Effect of encapsulation on absorption of sumatriptan tablets: data from healthy
      volunteers and patients during a migraine.
AB  - BACKGROUND: Some comparative trials of selective serotonin 1B/ID-agonists in
      migraine have reported -15% lower efficacy for sumatriptan tablets than that
      reported in placebo-controlled trials. OBJECTIVE: This study was designed to test
      the hypothesis that the encapsulation methods used to mask active drug may delay
      absorption of sumatriptan from dosing to 2 hours after dosing (the traditional
      end point in clinical trials of migraine treatment), an effect that may be
      enhanced by migraine-associated gastric stasis. METHODS: Two randomized, open
      label, 2-way crossover trials were conducted to evaluate the absorption and
      bioequivalence of conventional 50-mg sumatriptan tablets and encapsulated 50-mg
      sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome
      protocol SUM40270) and supine patients experiencing a migraine (Glaxo Wellcome
      protocol SUM40268). Absorption was assessed by calculating the area under the
      plasma concentration-time curve from dosing to 2 hours after dosing (AUC2) and
      the times to first measurable plasma concentration, 10 ng/mL, 20 ng/mL, and
      maximum plasma concentration. Data for the AUC from time zero to infinity and
      maximum plasma concentration were used to assess standard bioequivalence, which
      is considered to occur when the 90% CIs for the geometric mean treatment ratios
      (test/reference) fall between 0.8 and 1.25. RESULTS: Study 1 included 26 healthy
      subjects (73% men, 27% women; mean age, 39.1 years), and study 2 included 30
      patients with migraine (67% women, 33% men; mean age, 42.7 years). Sumatriptan
      absorption was delayed with the encapsulated tablet compared with the
      conventional tablet 0 to 2 hours after dosing, particularly during a migraine.
      AUC2 values with encapsulated sumatriptan compared with the conventional tablet
      were 21% lower in healthy volunteers (ratio of capsule/tablet, 0.79; 90% CI,
      0.588-1.050) and 27% lower in patients experiencing a migraine (ratio of
      capsule/tablet, 0.73; 90% CI, 0.519-1.023). Standard bioequivalence was
      demonstrated in both healthy volunteers and patients experiencing a migraine.
      CONCLUSIONS: Encapsulation delayed absorption of sumatriptan 0 to 2 hours after
      dosing, particularly during a migraine. This delay in absorption of the
      encapsulated form may account for the lower efficacy of sumatriptan in some
      comparative studies.

PMID- 11293558
TI  - Safety profile and tolerability of amprenavir in patients enrolled in an early
      access program.
AB  - BACKGROUND: The amprenavir (APV) early or expanded access program was designed to
      provide open-label APV to patients who would potentially receive benefit beyond
      that expected from currently available protease inhibitors (PIs) and who were at
      risk of disease progression before the drug's expected time of regulatory
      approval. OBJECTIVE: This study was conducted as part of an early access program
      to assess the safety profile and tolerability of APV in adults and children (> or
      =4 years of age) who were either intolerant to or, in the opinion of the
      patient's physician, virologically failing a previous PI-containing
      antiretroviral regimen. Specific CD4+ cell count and viral load limits were not
      imposed by this early access protocol. METHODS: This open-label, nonrandomized
      study was conducted at multiple sites throughout the United States. Adults
      received APV at a dosage of 1200 mg BID. Patients weighing <50 kg received APV at
      a dosage of 20 mg/kg BID for the solid formulation or 1.5 mL/kg BID for the
      liquid formulation. RESULTS: A total of 489 physicians registered for this
      program; 364 (74.4%) enrolled patients. The safety population of 2217 patients
      (2048 males [92.4%] and 169 females [7.6%] aged 2 to 74 years) received APV for a
      median duration of 85 days (range, 2-218 days). Patients in the intent-to-treat
      population (n = 1427) had extensive experience with antiretroviral therapy. Drug
      related treatment-emergent adverse events reported in >3% of patients in the
      safety population were nausea in 279 patients (12.6%), diarrhea in 197 patients
      (8.9%), rash in 177 patients (8.0%), vomiting in 148 patients (6.7%), and fatigue
      in 89 patients (4.0%). Adverse events and laboratory test abnormalities were
      graded for severity on a scale of 1 to 4 in accordance with AIDS Clinical Trials
      Group guidelines. Grade 3 treatment-emergent abnormal laboratory values
      regardless of causality occurring in >3% of patients were neutropenia in 69 of
      1887 patients (3.7%; grade 3 toxicity = 500-749/mm3) and elevated triglycerides
      in 80 of 1593 patients (5.0%; grade 3 toxicity = 751-1200 mg/dL). Most common
      grade 4 treatment-emergent laboratory abnormalities were elevated serum creatine
      phosphokinase levels in 36 of 1266 patients (2.8%; grade 4 = >6 times upper
      normal limit), elevated triglycerides in 39 of 1593 patients (2.4%), and
      neutropenia in 41 of 1887 patients (2.2%). CONCLUSIONS: The results of this large
      cohort of patients support the data from the phase II/III clinical development
      program and suggest that APV has an acceptable safety profile and is generally
      well tolerated when used in combination with other antiretroviral drugs in a
      heavily treatment-experienced, heterogeneous patient population.

PMID- 11293559
TI  - Efficacy, tolerability, and patient satisfaction with 50- and 100-mg sumatriptan
      tablets in those initially dissatisfied with the efficacy of 50-mg sumatriptan
      tablets.
AB  - BACKGROUND: Both 50- and 100-mg sumatriptan tablets are effective and well
      tolerated in the acute treatment of migraine. However, given a choice between the
      2 doses, many patients in clinical practice and clinical studies prefer the 100
      mg dose. OBJECTIVE: This study was designed to assess whether patients initially
      dissatisfied with the efficacy of 50-mg sumatriptan tablets would be satisfied
      with 100-mg sumatriptan tablets. METHODS: In phase 1 of the study, triptan-naive
      patients with migraine (International Headache Society diagnosis) received open
      label treatment of 3 migraine attacks with 50-mg sumatriptan tablets. At the end
      of phase 1, those who were dissatisfied with the efficacy but satisfied with the
      tolerability of 50-mg sumatriptan tablets entered phase 2 and were randomized in
      a double-blind, parallel-group fashion to receive either 50- or 100-mg
      sumatriptan tablets for the treatment of 3 attacks. Patients who were satisfied
      with the efficacy or dissatisfied with the tolerability of the 50-mg tablets in
      phase 1 were given the option of continuing open-label treatment with 50-mg
      sumatriptan tablets in phase 2. The primary end point was the percentage of
      patients satisfied with medication at the end of phase 2 double-blind treatment.
      Patient satisfaction with specific medication attributes was assessed using the
      Patient Perception of Migraine Questionnaire. RESULTS: Seven hundred twenty-two
      patients were enrolled in phase 1 of the study (the intent-to-treat population),
      609 of whom had evaluable satisfaction data at the end of open-label treatment.
      Three hundred twenty-six (54%) of these patients were satisfied with 50-mg
      sumatriptan tablets, whereas 283 (46%) were not satisfied. Among those who were
      dissatisfied, lack of efficacy was cited as the sole reason for dissatisfaction
      by 242 (86%). Two hundred thirty-one of those who were dissatisfied with efficacy
      only and wished to continue the study were randomized to double-blind treatment
      with either 50-mg sumatriptan tablets (n = 123; 82% female, 18% male; mean age,
      37.6 years) or 100-mg sumatriptan tablets (n = 108; 86% female, 14% male; mean
      age, 36.0 years). The remaining 310 patients elected to continue open-label
      treatment with 50-mg sumatriptan tablets. At the end of double-blind treatment,
      64 of 101 patients (63%) in the 100-mg group indicated that they were satisfied
      with treatment, compared with 55 of 113 (49%) in the 50-mg group (P = 0.031).
      Across the 3 attacks treated in the double-blind phase. headache relief 2 hours
      postdose was reported by 47% to 53% of patients in the 50-mg group and 45% to 60%
      of patients in the 100-mg group. The overall incidence of patients reporting > or
      =1 adverse event was 19% (23/123) in the 50-mg group and 22% (24/108) in the 100
      mg group. CONCLUSIONS: For most patients, 50 mg is the appropriate starting dose
      of sumatriptan tablets. In patients who experience inadequate relief with 50 mg,
      increasing the dose to 100 mg is an appropriate therapeutic option.

PMID- 11293561
TI  - Economic implications of early treatment of migraine with sumatriptan tablets.
AB  - BACKGROUND: Early treatment of migraine with sumatriptan 50 mg and 100 mg, while
      pain is mild, has been reported to enhance pain-free response 2 hours and 4 hours
      postdose and sustained pain-free response 2 to 24 hours postdose compared with
      treatment when pain has become moderate to severe. Early treatment with
      sumatriptan 50 mg and 100 mg also resulted in less redosing, which translated to
      a reduction in the mean number of doses used per migraine episode. OBJECTIVE: We
      examined the economic implications of early treatment with sumatriptan 50 mg and
      100 mg while pain is mild versus treatment when pain has become moderate to
      severe. METHODS: Using data from retrospective analyses of a dose-ranging
      clinical trial of sumatriptan (protocol S2CM09) involving 1003 patients, we
      estimated the mean cost per treatment success for a hypothetical population of
      1000 migraine patients who received treatment with sumatriptan 50-mg or 100-mg
      tablets early while pain was mild versus treatment when pain had become moderate
      to severe. RESULTS: With a conservative estimate of migraine frequency of 1.5
      episodes per month, the total cost of early migraine treatment with sumatriptan
      50 mg and 100 mg was reduced by $31.68 and $20.16, respectively, per patient per
      year. The average cost per pain-free treatment success was reduced by 32% to 57%
      with sumatriptan 50 mg and 100 mg if migraines were treated while pain was mild
      in intensity versus when pain had become moderate to severe. CONCLUSIONS:
      Treatment of migraine with sumatriptan 50-mg and 100-mg tablets is effective
      regardless of whether pain is mild, moderate, or severe. However, initiating
      treatment while pain is mild may be more cost-effective than delaying treatment
      until pain has become moderate to severe.

PMID- 11293560
TI  - Cost-minimization analysis of simvastatin versus atorvastatin for maintenance
      therapy in patients with coronary or peripheral vascular disease.
AB  - BACKGROUND: Previous health economic studies have demonstrated the cost
      effectiveness of simvastatin in the treatment of coronary heart disease (CHD)
      based on clinical results of the Scandinavian Simvastatin Survival Study. A prior
      analysis evaluated the "cost of getting to goal," but ignored all costs after
      titration. However, when evaluating the cost-effectiveness of long-term
      therapies, it is important to consider the maintenance costs as well. OBJECTIVE:
      The purpose of this study was to evaluate the maintenance costs of treatment with
      simvastatin versus that of treatment with another more recently available statin,
      atorvastatin, in a European context. METHODS: We assessed the long-term
      maintenance cost of simvastatin versus atorvastatin in terms of the cost of
      reducing low-density lipoprotein cholesterol (LDL-C) levels to the recommended
      goals based on a previously published clinical trial in patients with CHD. The
      analysis focused on the patients in the original clinical trial who were
      randomized to treatment with simvastatin or atorvastatin. Patients began therapy
      with 10 mg of simvastatin or atorvastatin; the dose of study drug was titrated
      every 12 weeks up to 40 mg simvastatin or 80 mg atorvastatin, with the addition
      of up to 8 g/d of cholestyramine until a modified European Atherosclerosis
      Society LDL-C goal (<2.84 mmol/L) was reached. As there was no significant
      difference between the 2 groups in resource utilization for adverse events, only
      drug costs were included. The calculated average annual maintenance cost was
      based on the distribution of the final daily dosing regimens and the public drug
      prices for each regimen. Individual country analyses were conducted using each
      local currency. RESULTS: There was no significant difference between groups in
      the percentage of patients reaching their LDL-C goal over the study period (80%
      for simvastatin-treated pa- tients vs 89% for atorvastatin-treated patients, P =
      0.135). However, the cost of maintaining a similar percentage of patients at
      their appropriate LDL-C levels was significantly lower in the simvastatin group
      compared with the atorvastatin group in 13 of the 17 countries assessed. In the
      remaining 4 countries, there was a cost advantage for simvastatin, but it did not
      reach statistical significance. CONCLUSIONS: Across Europe there was a
      significant reduction in the cost of maintaining patients at their appropriate
      LDL-C levels with simvastatin versus atorvastatin. The results of this analysis,
      along with the proven clinical benefits of simvastatin, support the use of this
      drug as the treatment of choice in the secondary prevention of CHD.

PMID- 11293562
TI  - Using forecasting models to estimate the effects of changes in the composition of
      claims for selective serotonin reuptake inhibitors on expenditures.
AB  - BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) as
      antidepressant therapy has increased considerably since the introduction of
      fluoxetine in 1989. By 1999, 3 of the 4 available SSRIs were among the top 10
      most frequently used drugs in the United States. In addition, SSRIs were one of
      the major contributors to the growth in psychotropic medication expenditures
      during the past 5 years. OBJECTIVE: The purpose of this article was to examine
      the utilization patterns of the 4 most commonly used SSRIs and their contribution
      to rising antidepressant medication expenditures among claimants in a publicly
      funded drug program. Using the results of forecasting models, we explored
      possible ways to control these growing expenditures. METHODS: Cross-sectional
      antidepressant claims and expenditure data from the Ontario Drug Benefits program
      for 1992 to 1998 were examined. Five scenarios were modeled in which future SSRI
      expenditures and claims were predicted using exponential smoothing models.
      RESULTS: If the historical patterns of use continued, a 20% increase in the 1998
      level of expenditures was expected to occur by the year 2000. Predicted
      expenditures are sensitive to the composition of the SSRI claims. Exclusive use
      of 1 of the 4 major SSRIs (fluvoxamine, fluoxetine, paroxetine, and sertraline)
      could decrease projected expenditures by 30% or increase them by 11%. An "equal
      shares" approach, in which each of the 4 SSRIs are used in equal proportions in
      the population, may reduce expenditures by approximately 8%. CONCLUSIONS: The
      current trends in the utilization data suggest that sertraline and paroxetine are
      being used as first-line treatments. The results of the forecasting models
      suggest that growing expenditures could be curbed if these 2 antidepressants were
      not used in that manner. Short of limiting the drugs available on benefit
      formularies, there may be a way to control costs through the use of a prescribing
      algorithm. Although our results support the use of fluoxetine for first-line SSRI
      treatment as a cost-control measure, we do not definitively recommend its
      adoption. These findings contribute to the discussion about using fixed versus
      flexible formularies as a potential cost-control mechanism.

PMID- 11293563
TI  - A comprehensive review of the antidiabetic agent rosiglitazone.

PMID- 11293564
TI  - A Plasmodium falciparum protein located in Maurer's clefts underneath knobs and
      protein localization in association with Rhop-3 and SERA in the intracellular
      network of infected erythrocytes.
AB  - We report on the characterization of monoclonal antibodies against Plasmodium
      falciparum schizonts, which recognize parasite proteins of 130 kDa and 20 kDa.
      The 130-kDa protein was released by alkaline sodium carbonate treatment,
      suggesting that the protein is a peripheral membrane protein, while the 20-kDa
      protein remained associated with the membranes following alkali treatment,
      suggesting it may be an integral membrane protein. Both proteins were localized
      to large cytoplasmic vesicles within the cytoplasm of trophozoite and schizont
      infected erythrocytes by immunofluorescence assay and confocal microscopy. Both
      proteins colocalized with Bodipy-ceramide in trophozoite and immature schizont
      infected erythrocytes, but not in segmenters. The 130-kDa protein was localized
      by immunoelectron microscopy (IEM) to Maurer's clefts underneath knobs in a
      knobby and cytoadherent (K +/ C+) P. falciparum strain. No IEM reactivity was
      obtained in a knobless and non-cytoadherent (K-/C-)

PMID- 11293565
TI  - Parasite-altered host behavior in the face of a predator: manipulation or not?
AB  - Parasitologists have generally accepted the idea that parasite-induced
      alterations in host behavior increase the chance for parasite survival and
      transmission or ensure the completion of its life cycle. The aim of the present
      study was to investigate modifications in the behavior of Taenia crassiceps
      infected BALB/c mice in the face of a predator. The experiments showed
      modifications in the response of infected mice in comparison with uninfected
      controls on exposure to a predator final host. However, different studies lead us
      to suggest that the observed modifications are likely to be a secondary effect of
      the impact of the parasite on host physiology and immunity that favors its
      development and proliferation.

PMID- 11293566
TI  - Invasive forms of Toxoplasma gondii, Leishmania amazonensis and Trypanosoma cruzi
      have a positive charge at their contact site with host cells.
AB  - We examined the surface charges of invasive forms of Toxoplasma gondii,
      Leishmania amazonensis, and Trypanosoma cruzi by atomic force microscopy and
      surface potential spectroscopy. We found that the specific part of the protozoan
      which makes initial contact with the host cell is positively charged. This
      indicates that the positive charge at the site of contact facilitates binding of
      the invasive protozoan to negatively charged host cells.

PMID- 11293567
TI  - Comparative study on the effects of three insecticides (fipronil, imidacloprid,
      selamectin) on developmental stages of the cat flea (Ctenocephalides felis Bouche
      1835): a light and electron microscopic analysis of in vivo and in vitro
      experiments.
AB  - The effects of three insecticides (fipronil, imidacloprid and selamectin) on
      developmental stages of cat fleas (Ctenocephalides felis) were studied in vivo,
      in vitro and by means of light and electron microscopy. The results were
      documented by video. Adult fleas were attached to the skin of dogs that had been
      treated 7 days before with one of the three compounds. Furthermore, adult fleas
      were exposed exclusively to the hair and skin debris of such treated dogs or were
      placed on filter papers that had been impregnated with one of these three
      compounds or with the blood of treated dogs. Larval fleas were exposed to hair of
      treated dogs, to debris obtained by combing treated dogs, to dried blood samples
      of treated dogs or were placed onto filter papers impregnated with one of the
      three compounds. In these experiments with adult and larval fleas, it was noted
      that none of the three insecticides had a repellent effect on adult or larval
      fleas. Imidacloprid was the only compound that acted exclusively by body contact,
      and was apparently taken up by adult and larval fleas via the thin, non
      sclerotized intersegmental membranes of the flea's body, shown when flea stages
      were exposed to hairs taken from dogs treated with one of the compounds or placed
      onto drug-impregnated filter papers. Imidacloprid killed larvae and adult fleas
      within 1 h, while it took at least 24 h until all adult fleas had died on
      fipronil- or selamectin-treated dogs, thus allowing longer feeding periods,
      increasing the risk of transmission of flea-derived diseases. Flea larvae covered
      with debris from dogs topically treated 7 days before with fipronil, imidacloprid
      or selamectin died, like the untreated control, within 16-28 h after exposure.
      This was, however, probably mainly due to a drying effect. Adult and larval fleas
      exposed to filter papers impregnated with the blood of treated dogs survived
      longer than 7 days, as did the untreated controls. All three drugs apparently
      acted on nerves and muscles and thus stopped motility.

PMID- 11293568
TI  - Association between nutritional indicators and infectivity of dogs seroreactive
      for Trypanosoma cruzi in a rural area of northwestern Argentina.
AB  - The association between the nutritional state of mongrel dogs naturally infected
      with Trypanosoma cruzi and their infectivity to Triatoma infestans bugs and
      immune response to Trypanosoma cruzi were studied in the rural village of Amama,
      northwestern Argentina. All of the 97 evaluated dogs were classified into one of
      three categories of external clinical aspect (ECA) based on the degree of muscle
      development, external evidence of bone structures, state of the hair of the coat,
      existence of fatty deposits, and facial expression. ECA was significantly
      associated with two nutritional indicators, hematocrit and skin-fold thickness,
      but not with total serum proteins. For all dogs, hematocrit was significantly
      correlated with skin-fold thickness. The 2-year survival probability decreased
      significantly from 60.7% for dogs with good ECA to 45.9% and 31.2% for those with
      regular and bad ECA, respectively. The age-adjusted relative odds of infection
      for Triatoma infestans xeno-diagnosis nymphs that fed once on a dog seroreactive
      for Trypanosoma cruzi decreased significantly as ECA improved, when tested by
      multiple logistic regression analysis. A delayed hypersensitivity reaction was
      observed in all of the seroreactive dogs with good ECA but only in 45-50% of
      those with regular or bad ECA. Dogs with bad ECA had a 2.6 and 6.3 times greater
      probability of infecting triatomines after a single full blood meal than dogs
      with regular or good ECA, respectively. Our study shows that the reservoir
      competence of dogs for Trypanosoma cruzi was associated with ECA, which is a
      surrogate and valid index of nutritional state.

PMID- 11293569
TI  - Hydrogenosome morphological variation induced by fibronectin and other drugs in
      Trichomonas vaginalis and Tritrichomonas foetus.
AB  - The hydrogenosome is a spherical organelle, found in some anaerobic protozoa,
      which participates in ATP and molecular hydrogen formation. The morphological
      alterations in hydrogenosomes induced by fibronectin, hydroxyurea and
      cytochalasin B in Trichomonas vaginalis and Tritrichomonas foetus are presented.
      We demonstrate that, under experimental conditions, the hydrogenosome presents a
      high diversity in size and shape, suggesting a mechanism that seems to compensate
      for the stress provoked by drugs. The following experimental procedures were
      used: (1) fibronectin-mediated endocytic activity, (2) 4 mM hydroxyurea for 15 h,
      and (3) 10 microg cytochalasin B/ml in the culture medium. The main alterations
      observed in hydrogenosomes were: (1) formation of giant hydrogenosomes, (2)
      presence of internal membranes, (3) increased diversity of non-spherical forms,
      some of them bizarre, (4) presence of sub-compartments in the matrix, as
      vesicles, (5) presence of ribosome-like particles on the outer hydrogenosomal
      membrane, (6) enlargement of the peripheral vesicle, and (7) continuity with
      membrane profiles.

PMID- 11293570
TI  - Linking specialisation to diversification in the Diplectanidae Bychowsky 1957
      (Monogenea, Platyhelminthes).
AB  - The hypothesis of a positive correlation between host specificity and taxonomic
      diversification was tested in a family of fish ectoparasites, the Diplectanidae
      Bychowsky 1957 (Monogenea). A comparative analysis of correlation of species
      richness with host specificity was performed using an adapted independent
      contrasts method. In order to control for phylogenetic effects, a phylogenetic
      tree of the genera in the Diplectanidae was reconstructed using morphological
      characters. The current taxonomy is retrieved in this phylogenetic hypothesis,
      except for the Murraytrematoidinae subfamily, which appears to be paraphyletic.
      There is no significant correlation between host specificity and taxonomic
      diversification in the Diplectanidae. The significance of this result is
      discussed, and different hypotheses which could have led to this observation are
      presented.

PMID- 11293571
TI  - Cryptosporidium parvum oocysts in zebra mussels (Dreissena polymorpha): evidence
      from the St Lawrence River.
AB  - Molluscan shellfish can recover and concentrate environmentally derived
      waterborne pathogens and can be used for the sanitary assessment of water
      quality. Oocysts of Cryptosporidium parvum (genotype 1) were identified in zebra
      mussels (Dreissena polymorpha) from the St. Lawrence River, Quebec. Approximately
      67 oocysts/ml of hemolymph and 129 oocysts/g of soft tissue were recovered. The
      adjusted concentration of oocysts per gram of tissue was 2.2 x 10(2), and
      approximately 4.4 x 10(2) oocysts were recovered from a single mussel. Zebra
      mussels can serve as biological indicators of waterborne contamination with
      Cryptosporidium.

PMID- 11293572
TI  - Praziquantel and  albendazole in the combined treatment of experimental hydatid
      disease.
AB  - The combination of praziquantel and albendazole (PZ + ABZ) used in the present
      study demonstrated an efficacy of 100% when used as chemoprophylactic treatment
      because no viable hydatid cysts developed after mice had been injected with
      protoscolices. However, when the PZ + ABZ combination was used for the treatment
      of 4-month secondary experimental hydatidosis, no significant difference was
      found between the control and treated mice, although severe damage to the cyst
      ultrastructure of the treated mice was observed.

PMID- 11293573
TI  - In vitro and in vivo antimalarial activity of ferrochloroquine, a ferrocenyl
      analogue of chloroquine against chloroquine-resistant malaria parasites.
AB  - Previous studies have shown that ferrochloroquine (FQ) exhibited an antimalarial
      activity against Plasmodium spp. The present work confirmed this activity,
      described the curative effect on P. vinckei and investigated the FQ toxicity in
      vitro and in vivo. The in vitro and in vivo growth inhibition of P. falciparum
      and P. berghei N, respectively, showed that FQ antimalarial activity was 1.5-10
      times more potent than chloroquine. FQ completely inhibited the in vivo
      development of both chloroquine-susceptible and resistant P. vinckei strains and
      protected mice from lethal infection at a dose of 8.4 mg kg(-1) day(-1) given for
      4 days subcutaneously or orally. This curative effect was 5-20 times more potent
      than chloroquine, according to the strains' resistance to chloroquine. At this
      curative dose, no clinical changes were observed in mice up to 14 days after the
      last administration. Nevertheless, the acute toxicity and lethality of
      ferrochloroquine seemed to be dependent on gastric surfeit. The FQ security index
      determined in vitro confirmed that it might be a promising compound.

PMID- 11293574
TI  - Development of high numbers of blood trypomastigotes of Trypanosoma cruzi in nude
      rats.
AB  - The development and pathogenicity of a Trypanosoma cruzi strain ("Chile 5") of
      low virulence were studied after infection of nude rats with different doses of
      blood trypomastigotes (10-10(7) parasites/rat). Peak parasitemias were correlated
      with the infection dose, which also influenced the mean survival times (26-36
      days post-infection). Within 26 or 27 days, a subcutaneous injection of 10(7)
      blood trypomastigotes developed to about 8-20 x 10(7) parasites/ml.

PMID- 11293575
TI  - Enlarged Chlamydia-like organisms as spontaneous infection of Acanthamoeba
      castellanii.

PMID- 11293576
TI  - Isolation and characterization of Sarcocystis from brain tissue of a free-living
      southern sea otter (Enhydra lutris nereis) with fatal meningoencephalitis.
AB  - A protozoan was isolated in cell culture from the brain of a free-ranging sea
      otter with fatal meningoencephalitis. The biological history of this otter, a
      study animal being monitored via an intraperitoneal radio transmitter, is
      summarized. Histologically, protozoal parasites were associated with areas of
      brain inflammation and necrosis in the cerebrum and cerebellum. Morphology and
      measurements of fixed, Giemsa-stained protozoal zoites growing on coverslips were
      consistent with Sarcocystis. These parasites reacted only with polyclonal
      antisera raised against S. neurona on immunohistochemistry. Cell culture-derived
      zoites reacted strongly with polyclonal antiserum to S. neurona on indirect
      fluorescent antibody tests. Amplification of portions of the 18S ribosomal DNA
      and the adjacent first internal transcribed spacer were performed. The resulting
      sequences were compared with published sequences from similar apicomplexan
      protozoa. This isolate (SO SN1), was indistinguishable from S. neurona, based on
      parasite morphology, antigenic reactivity and molecular characterization.

PMID- 11293577
TI  - Phenomenological study of the bed--wall friction in axially compressed packed
      chromatographic columns.
AB  - The properties of column beds prepared with slurries of Kromasil C8 in 12
      different solvents, using the same axial compression skid, were investigated. The
      extent of the consolidation of the column beds, their permeabilities, and the
      friction shear stress of these beds against the column wall were determined, as
      well as the column efficiencies (for an unretained tracer). The results of this
      study illustrate the influence of the wall effect on the consolidation. The
      permeability of columns consolidated under a constant compression stress was
      found to increase with increasing bed length. The bed-wall friction shear stress
      increases rapidly with increasing bed length and varies widely with the nature of
      the solvent used. No correlation was found between this shear stress and any
      physico-chemical property of the solvent. The best efficiency was observed for a
      column consolidated from a slurry in ethanol.

PMID- 11293578
TI  - Approximation function for the direct calculation of rate constants and Gibbs
      activation energies of enantiomerization of racemic mixtures from chromatographic
      parameters in dynamic chromatography.
AB  - An approximation function for enantioselective dynamic chromatography of racemic
      mixtures of interconverting enantiomers has been derived that allows the direct
      calculation of enantiomerization rate constants (k1 and k(-1)) and Gibbs
      activation energies of enantiomerization, deltaG++ , from chromatographic
      parameters, i.e., retention times of the enantiomers A and B ((t(A)R and t(B)R),
      peak widths at half height (WA and wB) and the relative plateau height
      (hplateau), without computer simulation. The reaction rate constants of
      enantiomerization, k(-1), obtained with this approximation function, have been
      validated by comparison with a simulated dataset of 15,625 chromatograms. The
      mean, standard deviation and confidence interval show a high correlation between
      the approximated and simulated rate constants. The average deviation from the
      Gibbs activation enthalpy of enantiomerization, deltaG++, has been estimated to
      be as small as about +/- 0.11 RT.

PMID- 11293579
TI  - Selectivity of stationary phases in reversed-phase liquid chromatography based on
      the dispersion interactions.
AB  - Selectivity of 15 stationary phases was examined, either commercially available
      or synthesized in-house. The highest selectivity factors were observed for solute
      molecules having different polarizability on the 3-(pentabromobenzyloxy)propyl
      phase (PBB), followed by the 2-(1-pyrenyl)ethyl phase (PYE). Selectivity of
      fluoroalkane 4,4-di(trifluoromethyl)-5,5,6,6,7,7,7-heptafluoroheptyl (F13C9)
      phase is lowest among all phases for all compounds except for fluorinated ones.
      Aliphatic octyl (C8) and octadecyl (C18) phases demonstrated considerable
      selectivity, especially for alkyl compounds. While PBB showed much greater
      preference for compounds with high polarizability containing heavy atoms than C18
      phase, F13C9 phase showed the exactly opposite tendency. These three stationary
      phases can offer widely different selectivity that can be utilized when one
      stationary phase fails to provide separation for certain mixtures. The retention
      and selectivity of solutes in reversed-phase liquid chromatography is related to
      the mobile phase and the stationary phase effects. The mobile phase effect,
      related to the hydrophobic cavity formation around non-polar solutes, is assumed
      to have a dominant effect on retention upon aliphatic stationary phases such as
      C8, C18. In a common mobile phase significant stationary phase effect can be
      attributed to dispersion interaction. Highly dispersive stationary phases such as
      PBB and PYE retain solutes to a significant extent by (attractive) dispersion
      interaction with the stationary phase ligands, especially for highly dispersive
      solutes containing aromatic functionality and/or heavy atoms. The contribution of
      dispersion interaction is shown to be much less on C18 or C8 phases and was even
      disadvantageous on F13C9 phase. Structural properties of stationary phases are
      analyzed and confirmed by means of quantitative structure-chromatographic
      retention (QSRR) study.

PMID- 11293580
TI  - Retention of ionizable compounds on HPLC. 6. pH measurements with the glass
      electrode in methanol-water mixtures.
AB  - The relationship, delta values, between the two rigorous pH scales, S(S)pH (pH
      measured in a methanol-water mixture and referred to the same mixture as standard
      state) and S(W)pH (pH measured in a methanol-water mixture but referred to water
      as standard state), in several methanol-water mixtures was determined (delta =
      S(W)pH-S(S)pH). Delta values were measured using a combined glass electrode and a
      wide set of buffer solutions. The results are consistent with those obtained with
      the hydrogen electrode. This confirms the aptness of the glass electrode to
      achieve rigorous pH measurements in methanol-water mixtures. An equation that
      relates delta and composition of methanol-water mixtures, and allows delta
      computation at any composition by interpolation, is proposed. Therefore, S(S)pH
      can be achieved from the experimental S(W)pH value and delta at any mobile phase
      composition. S(S)pH (or S(W)pH) values are related to the chromatographic
      retention of ionizable compounds through their thermodynamic acid-base constants
      in the methanol-water mixture used as mobile phase. These relationships were
      tested for the retention variation of several acids and bases with the pH of the
      mobile phase. Therefore, the optimization of the mobile phase acidity for any
      analyte can be easily reached avoiding the disturbances observed when W(W)pH is
      used.

PMID- 11293581
TI  - Determination of steroid sex hormones and related synthetic compounds considered
      as endocrine disrupters in water by fully automated on-line solid-phase
      extraction-liquid chromatography-diode array detection.
AB  - In this study, a procedure for the simultaneous determination in water of six
      estrogens (estradiol, estriol, estrone, ethynyl estradiol, mestranol, and
      diethylstilbestrol) and three progestogens (progesterone, norethindrone, and
      levonorgestrel), selected based on their abundance in the human body, their
      estrogenic potency, and the extent of their use in contraceptive pills, was
      developed. The procedure, based on the on-line solid-phase extraction (SPE) of
      the water sample and subsequent analysis by liquid chromatography/diode array
      detection (LC/DAD), allows for the monitoring of up to 16 samples in a completely
      automated, unattended way. The SPE experimental conditions were optimized and the
      polymeric cartridge PLRP-S selected out of four different cartridges evaluated.
      The chromatographic separation was carried out on a LiChrospher 100 RP-18 and
      detection was performed at 200, 225, and 240 nm. The applicability of the method
      to the analysis of various environmental water samples, including drinking water,
      groundwater, surface water and sewage treatment plant effluents, was evaluated.
      Method detection limits were in the range 10-20 ng/l. The method precision and
      accuracy were satisfactory with recovery percentages ranging from 96 to 111% and
      relative standard deviations lower than 3%. The technique is also considerably
      cheap, fast, and easy, and, therefore, very adequate for routing monitoring. To
      the authors' knowledge it constitutes the first work describing a fully
      automated, on-line methodology for the continuous monitoring of these compounds
      in water.

PMID- 11293582
TI  - Affinity chromatography of porcine pepsin on different types of immobilized 3,5
      diiodo-L-tyrosine.
AB  - The preparation of affinity sorbents containing immobilized iodinated derivatives
      of L-tyrosine for the affinity chromatography of porcine pepsin is described. The
      ligand was coupled either to Sepharose 4B or bead cellulose after the
      divinylsulfone activation or to Sepharose 4B after the activation with 2,4,6
      trichloro-1,3,5-triazine. The highest capacity for porcine pepsin was found in
      the case of 3,5-diiodo-L-tyrosine coupled to divinylsulfone-activated Sepharose.

PMID- 11293583
TI  - Application of ion-exchange cartridge clean-up in food analysis IV. Confirmatory
      assay of benzylpenicillin, phenoxymethylpenicillin, oxacillin, cloxacillin,
      nafcillin and dicloxacillin, in bovine tissues by liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - A multiresidue analytical method was developed for the confirmation of
      benzylpenicillin (PCG), phenoxymethylpenicillin (PCV), oxacillin (MPIPC),
      cloxacillin (MCIPC), nafcillin (NFPC) and dicloxacillin (MDIPC) in bovine tissues
      using electrospray ionization liquid chromatography-tandem mass spectrometry (LC
      ESI-MS-MS) with a product ion scan mode. All penicillins gave [M-H]-, [M-H-CO2]-
      and [M-H-141]- as the product ion, when [M-H]- was selected as the precursor ion.
      Combination of an ion-exchange cartridge clean-up and the LC-ESI-MS-MS method can
      reliably identify all of these penicillins fortified at a concentration of 0.05
      mg/kg in bovine tissues, including liver, kidney and muscle. The limits of
      confirmation satisfy the maximum residue limits for each of the penicillins
      established by the World Health Organization, US Food and Drug Administration,
      European Union and Japan.

PMID- 11293584
TI  - Simultaneous quantification of neutral and acidic pharmaceuticals and pesticides
      at the low-ng/l level in surface and waste water.
AB  - A new analytical method is presented that allows simultaneous determination of
      neutral and acidic pharmaceuticals and pesticides in natural waters. The
      compounds investigated include frequently used pharmaceuticals, i.e., the anti
      epileptic carbamazepine, four analgesic/anti-flammatory drugs (ibuprofen,
      diclofenac, ketoprofen and naproxen) and the lipid regulator clofibric acid and
      important pesticides including triazines, acetamides and phenoxy acids. Sample
      enrichment was achieved in one step with a newly developed solid-phase extraction
      procedure using the Waters Oasis HLB sorbent. The neutral compounds were analyzed
      by GC-MS in a first step, and then the acidic compounds after derivatization with
      diazomethane. Relative recoveries using isotope labeled internal standards were
      between 71 and 118% and the detection limits were in the range of 1 to 10 ng/l in
      drinking water, surface water and waste water treatment plant effluents
      (precision: 1-15%). The developed analytical method proved to be very durable
      during a 3-month field study and the target analytes were detected in
      concentrations of 5-3,500 ng/l in waste water treatment plant effluents, river
      water and lake water.

PMID- 11293585
TI  - Pyrolysis-capillary gas chromatography-mass spectrometry for the determination of
      polyvinyl chloride traces in solid environmental samples.
AB  - A novel method based on pyrolysis-capillary gas chromatography-mass spectrometry
      (CGC-MS) was developed for the quantitative analysis of polyvinylchloride (PVC)
      in solid environmental samples like sludge and dust. The samples are extracted
      and the extract is fractionated by solid-phase extraction (SPE). Possibly
      interfering biological and frequently occuring synthetic polymers are removed by
      this clean-up. The final extract is analyzed by pyrolysis-CGC-MS. Selective
      detection of PVC is performed by using specific markers in the pyrogram.
      Quantitation is done on naphthalene. Good linearity was obtained in a range from
      0.5 to 100 microg applied to the pyrolyser. The limit of quantitation (LOQ) in
      sludge and dust samples is 10 mg/kg dry mass. A correlation between PVC and
      phthalates was made for sewage sludge samples.

PMID- 11293586
TI  - New single-isomer chiral selector for capillary electrophoresis: the highly water
      soluble heptakis(2-N,N-dimethylcarbamoyl)-beta-cyclodextrin.
AB  - A new single isomer beta-cyclodextrin, the heptakis(2-N,N-dimethylcarbamoyl)-beta
      cyclodextrin (HDMC-beta-CD), has been synthesized and spectroscopically
      characterized. The outstanding feature of the new neutral beta-CD derivatives is
      their high solubility in water (>100 mM) and methanol. The resolution of chiral
      drugs can take advantage of this property. The resolution power of the new HDMC
      beta-CD is demonstrated by a selection of acidic and basic compounds using
      standard conditions.

PMID- 11293587
TI  - Capillary electrophoretic analysis of carbohydrates derivatized by in-capillary
      condensation with 1-phenyl-3-methyl-5-pyrazolone.
AB  - Our previous papers on capillary electrophoresis (CE) have shown that samples can
      be derivatized in a capillary and the derivatives can be analyzed immediately
      after derivatization, provided that the derivatization reaction is so rapid as to
      complete in seconds. The present paper presents extended application of in
      capillary derivatization to a much slower reaction such as the condensation of
      reducing carbohydrates with 1-phenyl-3-methyl-5-pyrazolone (PMP) which requires
      30 min at 70 degrees C in pre-column derivatization by manual operation. It was
      necessary to first drive the introduced plugs of sample and reagent solutions to
      put them together at the entrance of the heated portion of a capillary, then to
      allow the superimposed plugs to react for a relevant period. We showed how to
      determine the introduction times of the sample and the reagent solutions as well
      as intermediate running buffer, the voltages to be applied for plug driving and
      product analysis, and the duration of voltage application, all of which are
      important for effective in-capillary derivatization. An example of the analysis
      of maltooligosaccharides by this technique is presented. It was shown that
      maltooligosaccharides were quantitatively derivatized with PMP in 35 min at 57
      degrees C, and the derivatives could be analyzed in ca. 15 min by CE immediately
      after derivatization. Separation was satisfactory in 200 mM borate buffer, pH 8.2
      containing sodium dodecyl sulfate to a concentration of 200 mM. Although the
      theoretical plate number, and accordingly the resolution, were significantly
      lower than the corresponding values in pre-capillary derivatization, reasonable
      reproducibility was ensured for both migration time (RSD 3.5% on average) and
      peak area (RSD less than 3%) under the optimized conditions. It is notable that
      sample amount could be lowered to the 10 fmol level, in contrast to the 10 pmol
      level in pre-capillary derivatization. In addition, since the technique employed
      here (the modified at-inlet technique of in-capillary derivatization) is easily
      automated, the established system will be highly beneficial for routine analysis
      of carbohydrates. Analysis by this technique was also shown to be useful for
      kinetic study of the derivatization reaction.

PMID- 11293588
TI  - UV- and visible-excited fluorescence of nucleic acids separated by capillary
      electrophoresis.
AB  - UV- and visible-excited fluorescence detection strategies were compared for
      nucleic acids separated by capillary electrophoresis (CE). A dual-polymer sieving
      matrix consisting of hydroxypropylmethylcellulose and poly(vinylpyrrolidone) was
      used to separate DNA fragments from a 100-base pair ladder and RNA from
      individual cells. Two nucleic acid dyes, SYBR Gold and SYBR Green I, were
      evaluated for their performance at both UV (275 nm) and visible (488 nm)
      excitation wavelengths. While SYBR Gold-bound RNA from single cells yielded a
      substantially reduced UV-excited signal compared to that with visible excitation
      (as expected), the sensitivity of SYBR Gold-bound double-stranded DNA was
      comparable for UV and Vis excitation wavelengths. This study reveals the first
      demonstration of using SYBR Gold dyes for DNA detection following separation with
      CE and also the first example of SYBR-based detection of RNA sampled and
      separated from individual cells.

PMID- 11293589
TI  - Fast separation of pyrimidine derivatives by capillary electrochromatography on
      ion-exchange/reversed-phase mixed-mode stationary phases.
AB  - This work describes the use of mixed-mode stationary phases which exhibit both
      strong ion-exchange (either cation-exchange, SCX, or anion-exchange, SAX) and
      reversed-phase chromatographic characteristics in capillary
      electrochromatographic separations of pyrimidine derivatives. Different packing
      materials, namely C6, SCX/C6 and SAX/C6, were compared and the influence of the
      composition of the carrier electrolyte (concentration of acetonitrile and pH) on
      the retention behavior of the selected solutes was investigated. A separation of
      all eight pyrimidine derivatives could be obtained on a 6.5 cm column packed with
      the SAX/C6 stationary phase in less than 3 min, with good peak shapes and
      efficiencies in the range 39,000 to 81,000 plates per meter.

PMID- 11293590
TI  - Capillary electrophoretic determination of the constituents of Artemisiae
      Capillaris Herba.
AB  - Two capillary electrophoretic methods, a micellar electrokinetic electrophoretic
      (MEKC) one and a capillary zone electrophoretic (CZE) one, were developed for the
      separation of 12 constituents in Artemisiae Capillaris Herba. Detection at 254 nm
      with 20 mM sodium dodecyl sulfate and 20 mM sodium borate buffer (pH 9.82) in
      MEKC or with 25 mM sodium borate and 6.75 mg/ml 2,3,6-tri-O-methyl-beta
      cyclodextrin buffer in CZE was found to be the most suitable approach for this
      analysis. Within 42 min, the MEKC method could successfully separate 12 authentic
      constituents, whereof chlorogenic acid, however, appeared as a broad and split
      peak, and capillarisin and chlorogenic acid overlapped partially with other
      coexisting substances in crude extract of the herb. The CZE method could
      completely overcome these problems and was used to determine the amounts of
      capillarisin, chlorogenic acid, scopoletin and caffeic acid in the extract. The
      effect of buffers on the constituent separation and the validation of the two
      methods were discussed.

PMID- 11293591
TI  - Simultaneous direct high-performance liquid chromatographic enantioseparation of
      2-methylglycidol-1-benzyl ether and 2-methylglycerol-1-benzyl ether using a
      solvent-switching technique.
AB  - Simultaneous HPLC separation of the enantiomers of 3-benzyloxy-2-methyl-1,2
      propanediol and the corresponding 3-benzyloxy-2-methyl-1,2-propene oxide could be
      accomplished on amylose derived Chiralpak AD switching between 10% 2-propanol and
      3% 1,2-dimethoxyethane as polar modifier in n-heptane.

PMID- 11293592
TI  - Geographical distribution of variant Creutzfeldt-Jakob disease in Great Britain,
      1994-2000.
AB  - BACKGROUND: Geographical variation in the distribution of variant Creutzfeldt
      Jakob disease (vCJD) might indicate the transmission route of the infectious
      agent to man. We investigated whether regional incidences of vCJD were correlated
      with regional dietary data. METHODS: The National CJD Surveillance Unit
      prospectively identified 84 people with vCJD up to Nov 10, 2000, in Great
      Britain. Their lifetime residential histories were obtained by interviews with a
      close relative. Cumulative incidences of vCJD by standard region were calculated.
      Grid references for places of residence in 1991 were identified and evidence of
      geographical clusters were sought. Data on diet in the 1980s were analysed for
      regional correlations with vCJD incidence. The socioeconomic status of the places
      of residence of people with vCJD was compared with that of the general
      population. FINDINGS: vCJD incidence was higher in the north of Great Britain
      than the south. The rate ratio (north vs south) was 1.94 (95% CI 1.27-2.98). The
      mean Carstairs' deprivation score for areas of residence of people with vCJD was 
      0.09 (-0.73 to 0.55), which is close to the national average of zero. Regional
      rates of vCJD were correlated with consumption of other meat or meat products as
      classified and recorded by the Household Food Consumption and Expenditure Survey
      (r=0.72), but not with data from the Dietary and Nutritional Survey of British
      Adults. Five people with vCJD in Leicestershire formed a cluster (p=0.004).
      INTERPRETATION: Regional differences in vCJD incidence are unlikely to be due to
      ascertainment bias. We had difficulty determining whether regional variations in
      diet might cause these differences, since the results of dietary analyses were
      inconsistent.

PMID- 11293593
TI  - The uses of error: quality control.

PMID- 11293594
TI  - Effects of a large-scale intervention with influenza and 23-valent pneumococcal
      vaccines in adults aged 65 years or older: a prospective study.
AB  - BACKGROUND: The effectiveness of influenza and pneumococcal vaccination in the
      prevention of hospital admissions and death has not been assessed prospectively.
      We have therefore examined the effects of influenza and pneumococcal vaccination
      in individuals aged 65 years and older in a 3-year prospective study, between Dec
      1, 1998 and May 31, 1999. METHODS: All individuals in Stockholm County aged 65
      years or older (259,627) were invited to take part in a vaccination campaign
      against influenza and pneumococcal infection. We recorded for all vaccine
      recipients (100,242) name, and date of birth, and whether they had been given
      both or one of the vaccines. All individuals (> or = 65 years) admitted to
      hospital in Stockholm County with influenza and pneumonia related diagnoses were
      identified between Dec 1, 1998, and May 31, 1999. FINDINGS: The incidence (per
      100,000 inhabitants per year) of hospital treatment was lower in the vaccinated
      than in the unvaccinated cohort for all diagnoses: 263 versus 484 (-46% [95% CI
      34-56]) for influenza; 2199 versus 3097 (-29% [24-34)) for pneumonia; 64 versus
      100 (-36% [3-58]) for pneumococcal pneumonia; and 20 versus 40 (-52% [1-77]) for
      invasive pneumococcal disease. The total mortality was 57% (55-60) lower in
      vaccinated than in unvaccinated individuals (15.1 vs 34.7 deaths per 1000
      inhabitants). INTERPRETATION: These findings show that general vaccination leads
      to substantial health benefits and to a reduction of mortality from all causes in
      this age group.

PMID- 11293595
TI  - Clinical picture: gnathostomiasis.

PMID- 11293596
TI  - A swallowed toothbrush.

PMID- 11293597
TI  - Pitfalls in the use of thyrotropin concentration as a first-line thyroid-function
      test.
AB  - Measurement of thyrotropin concentration alone as a first-line thyroid-function
      test fails to indicate hypopituitarism in a number of patients. Using a
      combination of thyrotropin and thyroxine assays, we analysed 56,000 tests for a
      population of 471,000 over 12 months. 15 patients with clinically unsuspected
      hypopituitarism were detected, indicating that the occurrence of hypopituitarism
      might be underestimated.

PMID- 11293598
TI  - Chronic nervous-system effects of long-term occupational exposure to DDT.
AB  - Dichlorodiphenyltrichloroethane (DDT) is a compound with moderate toxicity that
      is judged to be safe for occupational use, although little is known about its
      long-term effects on the human nervous system. We investigated chronic nervous
      system effects of long-term occupational exposure to DDT by comparing the
      neurobehavioural performance of retired malaria-control workers with a reference
      group of retired guards and drivers. DDT-exposed workers did worse on tests
      assessing various neurobehavioural functions than controls; performance
      significantly deteriorated with increasing years of DDT application. Our results
      could not be explained by exposure to cholinesterase-inhibiting pesticides or
      other potential confounding factors.

PMID- 11293599
TI  - Brainstem activation specific to migraine headache.
AB  - Findings from functional imaging studies have shown activation of the brainstem
      during migraine without aura (MWOA) and activation of the hypothalamus during
      cluster headache. We assessed a patient with cluster headache and migraine by
      positron emission tomography during an active cluster headache after he had taken
      1.2 glyceryl trinitate. The patient developed a typical MWOA, during which we saw
      activation in the dorsal rostral brainstem. There was no activation in the region
      of the hypothalamus. Our findings provide evidence that migraine involves the
      brainstem, and show several areas involved in cluster headaches. Our data show
      the potential for objective distinction between primary headache syndromes with
      functional imaging, in disorders hitherto distinguished on clinical grounds.

PMID- 11293600
TI  - Nappy handling and risk of giardiasis.
AB  - We did a case-control study to identify modifiable risk factors for giardiasis in
      people aged 15-64 years living in Auckland, New Zealand. 183 patients with stool
      positive Giardia spp referred to community laboratories were compared with 336
      age-matched controls identified randomly from the Auckland telephone book.
      Exposure information for the previous 3 weeks was obtained retrospectively by
      telephone. Nappy changing was associated with a four-fold increased risk of
      infection after controlling for other confounders. We conclude that children
      wearing nappies could be an important source of giardia infection in the
      community.

PMID- 11293601
TI  - Aid will only help if African countries kickstart reform.

PMID- 11293602
TI  - Closing vaccination's "window of vulnerability".

PMID- 11293603
TI  - Striving for fair care in Guinea's war zone.

PMID- 11293604
TI  - Chinese government tackles environmental hazards.

PMID- 11293605
TI  - India to develop an AIDS vaccine.

PMID- 11293606
TI  - Canadian province opens door to two-tier health service.

PMID- 11293607
TI  - Ireland to review general practice services.

PMID- 11293608
TI  - Systemic lupus erythematosus.
AB  - This review covers major advances in clinical issues related to systemic lupus
      erythematosus (SLE) published between 1995 and 2000. The classification criteria
      for both SLE and antiphospholipid syndrome (APS) have been updated, and up to 19
      different subsets of neuropsychiatric lupus have been defined. New
      epidemiological data show that the incidence of new cases and the survival of
      patients with SLE are both increasing. Several randomised controlled trials have
      defined the role of cyclophosphamide, methotrexate, antimalarials, and hormonal
      treatment in the management of SLE. New data are available for drugs such as
      ciclosporin and thalidomide. Finally, several new treatments for severe
      refractory cases, such as mycophenolate mofetil and stem-cell transplantation,
      are being increasingly used. New data also refer to management of thrombosis in
      APS and high-risk pregnancies in women with SLE or APS.

PMID- 11293609
TI  - Revealing false paternity: some ethical considerations.

PMID- 11293610
TI  - A sense of language.

PMID- 11293611
TI  - Euthanasia in Europe.

PMID- 11293612
TI  - Euthanasia in Europe.

PMID- 11293613
TI  - Euthanasia in Europe.

PMID- 11293614
TI  - Applications of cholinesterase inhibitors.

PMID- 11293615
TI  - Pravastatin and coronary heart disease.

PMID- 11293616
TI  - Eradication of poliomyelitis.

PMID- 11293617
TI  - S100A8 and S100A9 in inflammatory diseases.

PMID- 11293618
TI  - Pain in Down's syndrome.

PMID- 11293619
TI  - Pain in Down's syndrome.

PMID- 11293620
TI  - Allergen exposure and asthma.

PMID- 11293621
TI  - Allergen exposure and asthma.

PMID- 11293622
TI  - Allergen exposure and asthma.

PMID- 11293623
TI  - Platelets and red cells in PrP(Sc) propagation in human beings.

PMID- 11293624
TI  - Heparin and aspirin in stroke.

PMID- 11293625
TI  - Laparoscopic surgery.

PMID- 11293626
TI  - Neonatal group B streptococcal disease.

PMID- 11293627
TI  - Misleading information leaflets for patients about antibiotics.

PMID- 11293628
TI  - Malaria epidemic in Burundi.

PMID- 11293629
TI  - Health care in Albania: what of the future?

PMID- 11293630
TI  - Access to fluconazole in less-developed countries.

PMID- 11293631
TI  - Wounding from biopsy and breast-cancer progression.

PMID- 11293632
TI  - Medical quotations.

PMID- 11293633
TI  - Ptomaine poisoning.

PMID- 11293634
TI  - Rethinking America's "War on Drugs" as a public-health issue.

PMID- 11293635
TI  - ABCs of secondary prevention of CHD: easier said than done.

PMID- 11293636
TI  - Antibiotics for preterm prelabour rupture of membranes and preterm labour?

PMID- 11293637
TI  - Genetic developments in hypoparathyroidism.

PMID- 11293638
TI  - Are some public-health problems better neglected?

PMID- 11293639
TI  - Should quality-of-life needs influence resource allocation?

PMID- 11293640
TI  - Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the
      ORACLE I randomised trial. ORACLE Collaborative Group.
AB  - BACKGROUND: Preterm, prelabour rupture of the fetal membranes (pPROM) is the
      commonest antecedent of preterm birth, and can lead to death, neonatal disease,
      and long-term disability. Previous small trials of antibiotics for pPROM
      suggested some health benefits for the neonate, but the results were
      inconclusive. We did a randomised multicentre trial to try to resolve this issue.
      METHODS: 4826 women with pPROM were randomly assigned 250 mg erythromycin
      (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid;
      n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until
      delivery. The primary outcome measure was a composite of neonatal death, chronic
      lung disease, or major cerebral abnormality on ultrasonography before discharge
      from hospital. Analysis was by intention to treat. FINDINGS: Two women were lost
      to follow-up, and there were 15 protocol violations. Among all 2415 infants born
      to women allocated erythromycin only or placebo, fewer had the primary composite
      outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%],
      p=0.08) than in the placebo group. Among the 2260 singletons in this comparison,
      significantly fewer had the composite primary outcome in the erythromycin group
      (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co
      amoxiclav plus erythromycin had no benefit over placebo with regard to this
      outcome in all infants or in singletons only. Use of erythromycin was also
      associated with prolongation of pregnancy, reductions in neonatal treatment with
      surfactant, decreases in oxygen dependence at 28 days of age and older, fewer
      major cerebral abnormalities on ultrasonography before discharge, and fewer
      positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus
      erythromycin were associated with prolongation of pregnancy, they were also
      associated with a significantly higher rate of neonatal necrotising
      enterocolitis. INTERPRETATION: Erythromycin for women with pPROM is associated
      with a range of health benefits for the neonate, and thus a probable reduction in
      childhood disability. However, co-amoxiclav cannot be routinely recommended for
      pPROM because of its association with neonatal necrotising enterocolitis. A
      follow-up study of childhood development and disability after pPROM is planned.

PMID- 11293641
TI  - Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II
      randomised trial. ORACLE Collaborative Group.
AB  - BACKGROUND: Preterm birth after spontaneous preterm labour is associated with
      death, neonatal disease, and long-term disability. Previous small trials of
      antibiotics for spontaneous preterm labour have reported inconclusive results. We
      did a randomised multicentre trial to resolve this issue. METHODS: 6295 women in
      spontaneous preterm labour with intact membranes and without evidence of clinical
      infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co
      amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565),
      or placebo (n=1569) four times daily for 10 days or until delivery, whichever
      occurred earlier. The primary outcome measure was a composite of neonatal death,
      chronic lung disease, or major cerebral abnormality on ultrasonography before
      discharge from hospital. Analysis was by intention to treat. FINDINGS: None of
      the trial antibiotics was associated with a lower rate of the composite primary
      outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both
      antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription
      was associated with a lower occurrence of maternal infection. INTERPRETATION:
      This trial provides evidence that antibiotics should not be routinely prescribed
      for women in spontaneous preterm labour without evidence of clinical infection.

PMID- 11293642
TI  - Clinical reality of coronary prevention guidelines: a comparison of EUROASPIRE I
      and II in nine countries. EUROASPIRE I and II Group. European Action on Secondary
      Prevention by Intervention to Reduce Events.
AB  - BACKGROUND: Patients with coronary heart disease (CHD) are the top priority for
      preventive cardiology. The first EUROASPIRE survey among patients with
      established CHD in nine countries in 1995-96 showed substantial potential for
      risk reduction. A second survey (EUROASPIRE II) was done in 1999-2000 in the same
      countries to see whether preventive cardiology had improved since the first. We
      compared the proportion of patients in both studies who achieved the lifestyle,
      risk-factor, and therapeutic goals recommended by the Joint European Societies
      report on coronary prevention. METHODS: The surveys were undertaken in the same
      selected geographical areas and hospitals in the Czech Republic, Finland, France,
      Germany, Hungary, Italy, the Netherlands, Slovenia, and Spain. Consecutive
      patients (men and women < or = 70 years of age) were identified after coronary
      artery bypass graft or percutaneous transluminal coronary angioplasty, or a
      hospital admission with acute myocardial infarction or ischaemia, and were
      interviewed at least 6 months later. FINDINGS: 3569 and 3379 patients were
      interviewed in the first and second surveys, respectively. The prevalence of
      smoking remained almost unchanged at 19.4% vs 20.8%. The prevalence of obesity
      (body-mass index > or = 30 kg/m2) increased substantially from 25.3% to 32.8%.
      The proportion with high blood pressure (> or = 140/90 mm Hg) was virtually the
      same (55.4% vs 53.9%), whereas the prevalence of high total cholesterol
      concentrations (> or = 5.0 mmol/L) decreased substantially from 86.2% to 58.8%.
      Aspirin or other antiplatelet therapy was as widely used in the second survey as
      the first (83.9% overall), and reported use of beta-blockers, angiotensin
      converting-enzyme inhibitors, and especially lipid-lowering drugs increased.
      INTERPRETATION: The adverse lifestyle trends among European CHD patients are a
      cause for concern, as is the lack of any improvement in blood-pressure
      management, and the fact that most CHD patients are still not achieving the
      cholesterol goal of less than 5 mmol/L. There is a collective failure of medical
      practice in Europe to achieve the substantial potential among patients with CHD
      to reduce the risk of recurrent disease and death.

PMID- 11293643
TI  - Irritable bowel syndrome: new agents targeting serotonin receptor subtypes.
AB  - Although the past few years have seen an exponential growth of compounds of
      potential interest for the treatment of functional gastrointestinal (GI) tract
      disorders, the gap that still exists between basic and clinical research is
      easily noticed if one considers the relative paucity of drugs that have received
      marketing authorisation for the treatment of irritable bowel syndrome (IBS).
      Traditional efficacy outcomes in drug development for IBS include the ability of
      the compound to affect GI tract motility (i.e. to exert a prokinetic or an
      antispasmodic effect), which is thought to be of importance if a motor disorder
      is the underlying pathophysiological mechanism. More recently, altered visceral
      sensitivity to a distending stimulus has been suggested to be a key
      pathophysiological feature, at least in some patients, and has become a target
      for therapeutic interventions. However, there is now growing consensus that the
      primary outcome measure in the treatment of functional disorders are those that
      reflect overall control of the patient's symptoms (pain, diarrhoea, constipation)
      in everyday situations such as the clinical global improvement scales. Although,
      in general, guidelines on the design of treatment trials for functional GI tract
      disorders advise against subcategorisation of patients according to the main
      symptom (because of symptom instability), subcategorisation indeed makes sense
      especially in IBS (constipation- or diarrhoea-predominant). Compounds with a
      specific indication for each subpopulation of patients are now emerging. The
      rationale for investigations on serotonin (5-hydroxytryptamine; 5-HT) receptor
      ligands in IBS rests mainly on the fact that serotonin, which may be released by
      enterochromaffin-like cells in the GI tract as well as from other sources, has a
      number of well documented motor effects on the GI tract and can produce
      hyperalgesia in several experimental models. Serotonin receptors belonging to the
      5-HT3 and 5-HT4 subtype are the most extensively studied in gastroenterology,
      although hitherto 'orphan' receptor subtypes, such as the 5-HT7 and the 5
      HT(1B/D) receptors, are now emerging. Among 5-HT3 receptor antagonists, alosetron
      was recently approved for the treatment of diarrhoea-predominant IBS and is an
      example of a compound that, at least theoretically, may act at multiple levels:
      by inhibiting visceral sensitivity, by increasing compliance, and by inhibiting
      excitatory 5-HT3 receptors located on both ascending and descending neuronal
      pathways involved in peristalsis. For this reason, 5-HT3 receptor antagonists may
      slow transit, hence the specific indication of alosetron in diarrhoea-predominant
      IBS. However, alosetron has been recently withdrawn by the manufacturer because
      of safety concerns. Hypomotility remains an attractive therapeutic target in IBS
      and the new generation of prokinetics includes several partial agonists at the 5
      HT4 receptor, such as tegaserod (HTF-919) and prucalopride (R0-93877). In
      addition, preliminary evidence suggests that 5-HT4 receptors may also be involved
      in the modulation of visceral sensitivity. Second-generation 5-HT4 receptor
      agonists seem to be devoid of the QT-prolonging effects observed in some clinical
      circumstances with cisapride and may be more active at the colonic level.
      Piboserod (SB-207266A) is a 5-HT4 receptor antagonist under development for the
      treatment of diarrhoea-predominant IBS. Finally, interest in 5-HT7 and 5-HT(1B/D)
      receptor subtypes stems from the observation that the former receptors mediate
      smooth muscle relaxation (at least in the human colon), whereas sumatriptan (a 5
      HT(1B/D) receptor agonist) can affect GI tract motility and visceral sensitivity.

PMID- 11293644
TI  - Cardiotoxicity with modern local anaesthetics: is there a safer choice?
AB  - The recognition that long-acting local anaesthetics, particularly bupivacaine the
      de facto standard long-acting local anaesthetic, were disproportionately more
      cardiotoxic than their shorter-acting counterparts stimulated the development of
      the bupivacaine congeners, ropivacaine and levobupivacaine. These agents, like
      all local anaesthetics, can produce cardiotoxic sequelae by direct and indirect
      mechanisms that derive from their mode of local anaesthetic actions, i.e.
      inhibition of voltage-gated ion channels. While all local anaesthetics can cause
      direct negative inotropic effects, ropivacaine and levobupivacaine are less
      cardiotoxic than bupivacaine judging by the larger doses tolerated in laboratory
      animal preparations before the onset of serious cardiotoxicity (particularly
      electro-mechanical dissociation or malignant ventricular arrhythmias).
      Additionally, they are less toxic to the CNS than bupivacaine judging by the
      larger doses tolerated before the onset of seizures. This may be clinically
      important because CNS effects may be involved in the production of serious
      cardiotoxicity. Preclinical studies in humans are a 'blunt instrument' in their
      ability to distinguish significant differences between these drugs because of the
      relatively small doses that can be used. Nevertheless, available evidence from
      human studies corroborates the preclinical laboratory animal studies. Because
      clinically significant differences between these drugs are more quantitative than
      qualitative, i.e. toleration of a larger dose before manifestation of toxicity,
      we have concluded that these newer agents have a lower risk of causing serious
      cardiotoxicity than bupivacaine. Thus, compared with bupivacaine, the newer
      agents may be seen as 'safer', but they must not be regarded as 'safe'.

PMID- 11293645
TI  - Bacteria-Triggered reactive arthritis: implications for antibacterial treatment.
AB  - Reactive arthritis (ReA) is definitely caused by an infection. Several
      observations suggest that the triggering microbe may persist in the tissues of
      the patient for a prolonged time. The obvious conclusion is to consider
      antibacterial treatment. In two instances antibacterial agents are of definite
      value: in the primary and secondary prevention of rheumatic fever and for early
      eradication of Borrelia burgdorferi in order to prevent development of the
      arthritis associated with Lyme disease. Altogether, clinical and experimental
      data exist to indicate that if antibacterial treatment of ReA can be started very
      early during the pathogenetic process, the disease can be prevented or the
      prognosis improved. In fully developed ReA, the value of antibacterial agents is
      less certain. All available evidence indicates that short term antibacterial
      treatment has no effect on the prognosis and final outcome of ReA, and the
      results with long term administration of antibacterials are also overall poor. In
      some instances sulfasalazine appears useful, rather as a result of its
      antirheumatic effect or influence on an underlying inflammatory bowel disease
      than its action as an antibacterial agent. Tetracyclines have also been found to
      have an effect on ReA, but again, this is probably due to their anti-inflammatory
      action rather than any antibacterial effect.

PMID- 11293646
TI  - An update on the role of nitrofurans in the management of urinary tract
      infections.
AB  - There have been few recent reviews of the nitrofurans in the literature, and none
      include recently available data on the use of nitrofurazone (nitrofural) in the
      prevention of catheter-associated urinary tract infection (CAUTI). Nitrofurazone
      and nitrofurantoin are the only nitrofurans that have become established in
      clinical use in the 20th century. These 2 nitrofurans have remained clinically
      useful against a wide spectrum of gram-positive and gram-negative bacteria,
      including many strains of common urinary tract pathogens. Today, the primary use
      of nitrofurantoin is as an oral antibacterial treatment for genitourinary
      infections. Nitrofurazone is primarily used as a topical antibacterial agent in
      burns and skin grafts and recently was approved for the prophylaxis of CAUTI. The
      recent development of a nitrofurazone-impregnated catheter as a novel modality in
      the prevention of CAUTI reflects a renewed interest in the effectiveness of
      nitrofurans. In an era when concern about bacterial resistance to many anti
      infective agents is growing, the nitrofurans have continued to be active against
      organisms that have developed resistance to antibacterials. The presence of
      multiple mechanisms of action for the nitrofurans might be expected to reduce the
      ability of bacteria to develop resistance. Considering that an emergence of
      resistance to the nitrofurans has not appreciably occurred after several decades
      of clinical use, the nitrofurans may be unique among common antibacterial agents
      in this regard.

PMID- 11293647
TI  - Does allergen immunotherapy alter the natural course of allergic disorders?
AB  - Allergy in patients with atopy is caused by clinical adverse reactions to
      environmental antigen, which is often associated with allergen-specific
      immunoglobulin (Ig)E production. Since allergy reflects an inappropriate
      immunological reaction, a therapeutic approach related to immunology is likely to
      actively alter the natural course of allergic disorders. Allergen immunotherapy,
      known at various times as desensitisation or hyposensitisation, is very recently
      defined by the World Health Organization as therapeutic vaccines for allergic
      diseases. At present, it has become a common clinical practice in selected
      patients for the treatment and prevention of the recurrence of allergic disorders
      caused by insect venoms and has proven to be effective in changing the course of
      allergic responses induced by grass and tree pollen, animal hair and dander,
      house dust mite and mold, as demonstrated by improvement in clinical symptoms,
      skin prick test and medication scores. Reported effects of allergen immunotherapy
      on the natural course of allergic disorders include (i) prevention of reaction
      following re-sting in insect venom allergy; (ii) prevention or decrease the rate
      of the natural progress of allergic rhinitis to asthma; and (iii) inhibition of
      new sensitisation in monosensitised children. Many aspects of the immune
      responses associated with allergic disorders, including antibody production,
      cytokine secretion, T cell activation and local inflammatory reactions, are found
      to be significantly altered during and/or after immunotherapy. Specifically, the
      ratio of allergen-specific IgG4 to IgG1 correlates well with positive clinical
      outcome caused by allergen immunotherapy in patients with pollen-allergy.
      Allergen immunotherapy affects the cytokine profile of allergen-specific T cells
      and switches T(H)2 type immune responses in patients with atopy towards T(H)0 or
      T(H)1 type responses. Although the changes in the absolute value of T(H)1 or
      T(H)2 cytokines appear quite variable, the increase in the ratio of T(H)1/T(H)2
      cytokines is very consistent among published reports, especially in the late
      stage of treatment. Accumulating evidence indicates that appropriate
      immunotherapy prevents the onset of new sensitisation and prevents the progress
      of allergic rhinitis to asthma. Although the changes in B cell and T cell
      responses, especially IgG antibodies and T(H)1/T(H)2 cytokine production, may be
      the major mechanism underlying the clinical efficacy of allergen immunotherapy
      and the prevention of the development of allergic phenotypic changes, multiple
      mechanisms may be involved in the outcome of alteration of the natural course of
      allergic disorders.

PMID- 11293648
TI  - The myocardial Na+/H+ exchanger: a potential therapeutic target for the
      prevention of myocardial ischaemic and reperfusion injury and attenuation of
      postinfarction heart failure.
AB  - The myocardial Na+/H+ exchange (NHE) represents a major mechanism for pH
      regulation during normal physiological processes but especially during ischaemia
      and early reperfusion. However, there is now very compelling evidence that its
      activation contributes to paradoxical induction of cell injury. The mechanism for
      this most probably reflects the fact that activation of the exchanger is closely
      coupled to Na+ influx and therefore to elevation in intracellular Ca2+
      concentrations through the Na+/Ca2+ exchange. The NHE is exquisitely sensitive to
      intracellular acidosis; however, other factors can also exhibit stimulatory
      effects via phosphorylation-dependent processes. These generally represent
      various autocrine and paracrine as well as hormonal factors such as endothelin-1,
      angiotensin II and alpha1-adrenoceptor agonists, which probably act through
      receptor-signal transduction processes. Thus far, 6 NHE isoforms have been
      identified and designated as NHE1 through NHE6. All except NHE6, which is located
      intracellularly, are restricted to the sarcolemmal membrane. In the mammalian
      myocardium the NHE1 subtype is the predominant isoform, although NHE6 has also
      been identified in the heart. The predominance of NHE1 in the myocardium is of
      some importance since, as discussed in this review, pharmacological development
      of NHE inhibitors for cardiac therapeutics has concentrated specifically on those
      agents which are selective for NHE1. These agents, as well as the earlier
      nonspecific amiloride derivatives have now been extensively demonstrated to
      possess excellent cardioprotective properties, which appear to be superior to
      other strategies, including the extensively studied phenomenon of ischaemic
      preconditioning. Moreover, the salutary effects of NHE inhibitors have been
      demonstrated using a variety of experimental models as well as animal species
      suggesting that the role of the NHE in mediating injury is not species specific.
      The success of NHE inhibitors in experimental studies has led to clinical trials
      for the evaluation of these agents in high risk patients with coronary artery
      disease as well as in patients with acute myocardial infarction (MI). Recent
      evidence also suggests that NHE inhibition may be conducive to attenuating the
      remodelling process after MI, independently of infarct size reduction, and
      attenuation of subsequent postinfarction heart failure. As such, inhibitors of
      NHE offer substantial promise for clinical development for attenuation of both
      acute responses to myocardial as well as chronic postinfarction responses
      resulting in the evolution to heart failure.

PMID- 11293651
TI  - Taxonomy of the genus Paracoccus.

PMID- 11293652
TI  - Microbiological and electron microscopic studies of urea treated Rhizobium sp.
      cells.
AB  - Microbiological investigation of urea treated Rhizobium sp. cells showed a
      gradual decrease of colony forming unit from initial 100% to 2.13% value. Maximum
      effect was reached at 90 min onwards. The liquid holding recovery in phosphate
      buffer saline at pH 7.0 also was studied. Electron microscopic studies revealed
      important structural changes in treated cells.

PMID- 11293650
TI  - Drug treatment of scleroderma.
AB  - Scleroderma or systemic sclerosis is a rare condition with many clinical
      manifestations including Raynaud's phenomenon. As with many other rarely
      encountered diseases, drug therapy for scleroderma is often empirical with little
      evidence in the form of randomised controlled trials to aid drug choice.
      Raynaud's phenomenon has been recognised for well over 100 years. A considerable
      number of clinical trials in this area have demonstrated unequivocally the use of
      nifedipine as a gold standard. Large studies have also demonstrated the efficacy
      of iloprost. However, this drug is not as yet licensed for scleroderma in the UK
      or elsewhere. This presents an additional problem as information regarding the
      use and administration of unlicensed drugs is often sparse and post-marketing
      surveillance to assess safety is not routinely performed. When looking at the
      other distinct conditions encountered by a patient with scleroderma it becomes
      evident that trials are often retrospective or limited in patient numbers.
      Studies investigating the use of methotrexate, antithymocyte globulin and
      cyclophosphamide in patients with scleroderma have been very small and in some
      cases not well designed. The major work on penicillamine was a retrospective
      trial. Again these drugs are not licensed for use in scleroderma. Drug therapy
      for pulmonary hypertension secondary to scleroderma closely follows that outlined
      for primary pulmonary hypertension. In the US there is a patient registry for
      primary pulmonary hypertension that has enabled well designed, large-scale
      studies to demonstrate the benefits of epoprostenol in severe primary pulmonary
      hypertension. Hence, research in this area has progressed considerably over the
      last decade. Clearly, a considerable amount of work is being carried out to
      elucidate new treatment regimens for scleroderma, however, evaluation of these
      studies is proving to be a difficult process. Designated hospital centres for
      scleroderma (there are currently 2 in the UK), better markers of disease activity
      and methods to measure improvement or deterioration in affected organs, should
      enable research into aetiology, disease progression and treatment to be carried
      out on a larger scale resulting, hopefully, in more conclusive answers.

PMID- 11293649
TI  - Nocturnal asthma uncontrolled by inhaled corticosteroids: theophylline or long
      acting beta2 agonists?
AB  - Asthma is an inflammatory disease of the airways that is frequently characterised
      by marked circadian rhythm. Nocturnal and early morning symptoms are quite common
      among patients with asthma. Increased mortality and decreased quality of life are
      associated with nocturnal asthma. Although numerous mechanisms contribute to the
      pathophysiology of nocturnal asthma, increasing evidence suggests the most
      important mechanisms relate to airway inflammation. According to international
      guidelines, patients with persistent asthma should receive long term daily anti
      inflammatory therapy. A therapeutic trial with anti-inflammatory therapy alone
      (without a long-acting bronchodilator) should be assessed to determine if this
      therapy will eliminate nocturnal and early morning symptoms. If environmental
      control and low to moderate doses of inhaled corticosteroids do not eliminate
      nocturnal symptoms, the addition of a long-acting bronchodilator is warranted.
      Long-acting inhaled beta2 agonists (e.g. salmeterol, formoterol) are effective in
      managing nocturnal asthma that is inadequately controlled by anti-inflammatory
      agents. In addition, sustained release theophylline and controlled release oral
      beta2 agonists are effective. In patients with nocturnal symptoms despite low to
      high doses of inhaled corticosteroids, the addition of salmeterol has been
      demonstrated to be superior to doubling the inhaled corticosteroid dose. In
      trials comparing salmeterol with theophylline, 3 studies revealed salmeterol was
      superior to theophylline (as measured by e.g. morning peak expiratory flow,
      percent decrease in awakenings, and need for rescue salbutamol), whereas 2
      studies found the therapies of equal efficacy. Studies comparing salmeterol to
      oral long-acting beta2 agonists reveal salmeterol to be superior to terbutaline
      and equivalent in efficacy to other oral agents. Microarousals unrelated to
      asthma are consistently increased when theophylline is compared to salmeterol in
      laboratory sleep studies. In addition to efficacy data, clinicians must weigh
      benefits and risks in choosing therapy for nocturnal asthma. Long-acting inhaled
      beta2 agonists are generally well tolerated. If theophylline therapy is to be
      used safely, clinicians must be quite familiar with numerous factors that alter
      clearance of this drug, and they must be prepared to use appropriate doses and
      monitor serum concentrations. Comparative studies using validated, disease
      specific quality of life instruments (e.g. Asthma Quality of Life Questionnaire)
      have shown long-acting inhaled beta2 agonists are preferred to other long-acting
      bronchodilators. Examination of costs for these therapeutic options reveals that
      evening only doses of long-acting oral bronchodilators are less expensive than
      multiple inhaled doses. However, costs of monitoring serum concentrations, risks,
      quality of life and otheroutcome measures must also be considered. Long-acting
      inhaled beta2 agonists are the agents of choice for managing nocturnal asthma in
      patients who are symptomatic despite anti-inflammatory agents and other standard
      management (e.g. environmental control). These agents offer a high degree of
      efficacy along with a good margin of safety and improved quality of life.

PMID- 11293653
TI  - Demethylation of [14C]-labelled veratric acid and oxidation of methanol and
      formaldehyde by the white-rot fungus Phlebia radiata.
AB  - Veratric acids 14C-labelled in carboxyl group, 3-OCH3, 4-OCH3, or aromatic ring
      together with unlabelled veratric acid were supplemented in the cultures of the
      white-rot fungus Phlebia radiata. The effect of various carbon sources on the
      release of 14CO2 was studied. Veratric acid was readily decarboxylated, maximally
      already on day 1 from the addition of [14COOH]-veratric acid. High amounts (4%)
      of glucose slightly repressed the decarboxylation. In medium supplemented with
      cellulose the methoxyl group in position 4 was much more readily mineralized to
      CO2 than the group in position 3. The maximum evolution was achieved on day 5,
      two days from the addition. Cellulose did not repress methanol oxidation but
      repression of methanol oxidation by glucose was detected in media supplemented
      with [O14CH3]-veratric acids and 14CH3OH. However, glucose did not repress
      oxidation of H14CHO. The apparent uptake of 14C by fungal mycelium, especially
      from methoxyl groups, but also from the aromatic ring, may partially be due to
      the strong slime formation observed in cellobiose medium. Also in cellobiose
      medium apparent uptake of 14C from 14C-labelled methoxyl groups was observed.

PMID- 11293654
TI  - Isolation and insecticidal effects of some bacteria from Euproctis chrysorrhoea
      L. (Lepidoptera: Lymantriidae).
AB  - In this study, we investigated the bacterial pathogens of Euproctis chrysorrhoea
      and tested for their insecticidal activities. Based on colony color and
      morphology, four isolates were determined. According to morphological,
      physiological and biochemical characters of the isolates, they were identified as
      Enterobacter aerogenes, Lactobacillus sp., Bacillus thuringiensis and Micrococcus
      luteus. The insecticidal effects of these bacterial isolates on third-fourth
      instar larvae of Euproctis chrysorrhoea were investigated. The highest
      insecticidal effect determined on this pest is 68% with Bacillus thuringiensis.
      The effects of the other isolates are 45% with Enterobacter aerogenes, 15%
      Micrococcus luteus and 0% with Lactobacillus sp.

PMID- 11293655
TI  - Growth, zearalenone production and some metabolic activities of Fusarium
      moniliforme under salt stress.
AB  - With a increasing salinity, a decrease in the growth rate of Fusarium moniliforme
      was observed. The percentage of germinated conidia decreased with increasing
      salinity (% germination ranged from 80.3% at 0.0% NaCl to 0.0% at 15% NaCl).
      Concentration of 12.5% NaCl produced the highest chlamydospore-like structures.
      Concentration of 5% NaCl increased zearalenone production which decreased with
      increasing salt stress. Escherichia coli was more tolerant to the toxin than
      Bacillus subtilis. The total amount of lipids produced by F. moniliforme changed
      with increasing the concentration of NaCl in the growth medium. The genomic DNA
      of the control and treated samples showed a common band of more than 20
      kilobases. Similar RAPD-PCR patterns were also produced.

PMID- 11293656
TI  - Effect of Staphylococcus aureus serine proteinase on the respiratory burst in
      phagocytic cells in vitro.
AB  - The in vitro effects of the Staphylococcus aureus serine proteinase (SASP) on the
      respiratory burst of human blood mononuclear phagocytes and rat lung macrophages
      were investigated. The generation of reactive oxygen species (ROS), determined by
      means of luminol-based chemiluminescence, was stimulated by treatment with SASP
      in both types of the defense cells. Cell activation depended on the concentration
      of the enzyme and the response of monocytes was an order of magnitude stronger
      relative to macrophages. The chemiluminescence emission kinetics were different
      for both cell types and the maximum signal was achieved in approximately 3 and 17
      min, respectively. In experiments involving further cell activation by latex
      particles, macrophages pretreated with various SASP concentrations reacted with
      enhanced ROS generation whereas for monocytes, the latex-induced
      chemiluminescence was weakened by the enzyme. The results concerning the
      modification of the phagocytic host cell activity by SASP suggest that this
      enzyme might play an important role in pathomechanisms of staphylococcal
      infections in vivo.

PMID- 11293657
TI  - The effect of statherin and its shortened analogues on anaerobic bacteria
      isolated from the oral cavity.
AB  - The susceptibility (MIC) of 44 strains of anaerobic bacteria isolated from the
      oral cavity and 3 standard strains to statherin and its C-terminal fragments with
      sequences QYQQYTF, YQQYTF, QQYTF, QYTF and YTF was determined by means of plate
      dilution technique in Brucella agar with 5% content of defibrinated sheep's
      blood, menadione and hemin. The culture was anaerobic. As shown, at
      concentrations from 12.5 to 100 microg/ml statherin and its C-terminal fragments
      inhibited the growth of anaerobic bacteria isolated from the oral cavity.
      Peptostreptococcus strains were the most susceptible to statherin and YTF (MIC <
      or = 12.5 mg/ml), whereas the most susceptible to the peptides investigated were
      Fusobacterium necrogenes and Fusobacterium necrophorum strains: QYQQYTF, YQQYTF,
      QQYTF, QYTF (MIC < or = 12.5 microg/ml). Prevotella oralis, Bacteroides forsythus
      and Bacteroides ureolyticus strains exhibited the lowest susceptibility (MIC >
      100 microg/ml). When analysing the bacteriostatic activity of statherin it should
      be pointed out that the concentrations of this peptide used in microbiological
      investigations are within the range of physiological concentrations determined
      for whole saliva when at rest and stimulated in healthy donors of 19-25 years of
      age. Since the anaerobes investigated may be involved in the diseases of
      periodontum, the results presented seem to have also a practical aspect, i.e. a
      possibility to apply the C-terminal fragments of statherin as a novel therapeutic
      agent, affecting favourably the oral cavity.

PMID- 11293658
TI  - Prediction of a novel RNA 2'-O-ribose methyltransferase subfamily encoded by the
      Escherichia coli YgdE open reading frame and its orthologs.
AB  - The amino acid sequence of the RNA 2'-O-ribose methyltranserase RrmJ was used as
      a probe for detecting putative homologs through iterative searches of genomic
      databases. We found a previously unannotated YgdE open reading frame (ORF) in the
      genome sequences of Escherichia coli and other gamma-Proteobacteria, which shares
      key features with RrmJ, despite the mutual sequence similarity of these proteins
      is relatively low. The predicted structural compatibility and the conservation of
      all functionally important residues between RrmJ and YgdE strongly suggests that
      the newly identified methyltranserase also modifies 2'-OH groups of ribose. The N
      terminal region of YgdE, which has no counterpart in RrmJ, is predicted to form
      an independent domain, possibly involved in target recognition.

PMID- 11293659
TI  - Quantitative detection of CMV DNA by PCR and hybridizaton methods in renal
      transplant recipients.
AB  - The comparison of two quantitative tests: hybridization (Murex Hybrid Capture
      System) and PCR (COBAS AMPLICOR CMV Monitor) detected CMV DNA was made.
      Investigation of viral load in serum by PCR gave better correlation with clinical
      manifestation in renal transplant recipients.

PMID- 11293660
TI  - Plasmid occurrence and diversity in the genus Paracoccus.
AB  - The results of screening for the occurrence of plasmids in several strains
      representing 11 out of 13 species of the genus Paracoccus are presented. We show
      that plasmids (ranging in size from 2.7 to above 450 kb) are widely distributed
      in this genus. Only one tested strain (P. alkenifer) appears to be plasmid-free.
      The majority of the strains harbour at least two plasmids, one of which usually
      fits into the class of megaplasmids.

PMID- 11293661
TI  - Hypothesis: is a failure to prevent bacteriolysis and the synergy among microbial
      and host-derived pro-inflammatory agonists the main contributory factors to the
      pathogenesis of post-infectious sequelae?

PMID- 11293662
TI  - Activity of the leukocyte NADPH oxidase in whole neutrophils and cell-free
      neutrophil preparations stimulated with long-chain polyunsaturated fatty acids.
AB  - Fish oils are known for their anti-inflammatory effects. In this paper we
      investigated the influence of eicosapentaenoic acid and docosahexaenoic acid
      (omega-3 fatty acids), as well as docosapentaenoic acid, a metabolic product of
      omega-3 fatty acid metabolism, on O2(-)-production catalyzed by the NADPH oxidase
      in whole neutrophils and in a cell-free system consisting of neutrophil membranes
      and cytosol. As a standard we used arachidonic acid (an omega-6 fatty acid) found
      in a high proportion in the Western diet, and known as an effective activator of
      the oxidase in both systems. Our data show that with omega-3 fatty acids, the O2(
      )-production in both systems is reduced as compared to the effect of arachidonic
      acid. The effects are more pronounced with increasing carbon chain length and
      increasing numbers of double bonds. Our results suggest another mechanism besides
      the inhibition of eicosanoid and cytokine production to explain the beneficial
      effects of fish oils in reducing inflammation.

PMID- 11293663
TI  - Suppression of lung inflammation in rats by prevention of NF-kappaB activation in
      the liver.
AB  - Activation of NF-kappaB and production of NF-kappaB-dependent chemokines are
      thought to be involved in the pathogenesis of neutrophilic lung inflammation.
      Calpain-1 inhibitor (CI-1) blocks activation of NF-kappaB by preventing
      proteolysis of the inhibitory protein IkappaB-alpha by the ubiquitin/proteasome
      pathway. We hypothesized that inhibition of proteasome function with CI-1 would
      block NF-kappaB activation in vivo after intraperitoneal (i.p.) treatment with
      bacterial lipopolysaccharide (LPS), and that NF-kappaB inhibition would be
      associated with suppression of chemokine gene expression and attenuation of
      neutrophilic alveolitis. We treated rats with a single i.p. injection of CI-1 (10
      mg/kg) two hours prior to i.p. LPS (7 mg/kg). Treatment with Cl-1 prevented
      degradation of IkappaB-alpha and activation of NF-kappaB in the liver in response
      to LPS; however, Cl-1 treatment had no detected effect on NF-kappaB activation in
      lung tissue. CI-1 treatment prior to LPS resulted in 40% lower MIP-2
      concentration in lung lavage fluid compared to rats treated with vehicle prior to
      LPS (502 +/- 112 pg/ml vs. 859 +/-144 pg/ml, P < 0.05). In addition, CI-1
      treatment substantially inhibited LPS-induced neutrophilic alveolitis (2.7+ /-
      1.2 x 10(5) vs. 43.7 +/- 12.2 x 10(5) lung lavage neutrophils, P < 0.01). These
      data indicate that NF-kappaB inhibition in the liver can alter lung inflammation
      induced by systemic LPS treatment and suggest that a liver-lung interaction
      contributes to the inflammatory response of the lung.

PMID- 11293664
TI  - Pattern of cytokine and adhesion molecule mRNA in hapten-induced relapsing colon
      inflammation in the rat.
AB  - We examined the mRNA expression of cytokines, chemokines, integrins, and
      selectins in colon lesions of rat colitis with a semi-quantitative RT-PCR assay.
      Rat colitis was induced by trinitrobenzene sulfonic acid (TNBS) in 50% ethanol.
      Within 24 h, an acute inflammation occurred with hyperemia, edema, necrosis and
      an intense infiltration of granulocytes in the mucosa. The lesion proceeded into
      a T-lymphocyte/monocyte-driven chronic inflammation for two weeks and healed in 6
      weeks. An acute inflammation recurred at the same site when the recovered animals
      were systemically injected with TNBS. We isolated RNA from colon tissue at 24 h,
      1, 2, 4, 6 weeks after TNBS treatment and from the relapsed animals. The mRNA for
      cytokines IL-1beta, IL-6, IL-10 and the chemokines CINC, MIP-1alpha, MCP-1 were
      significantly (P < 0.05) elevated and persisted for 2 weeks, decreased in 6 weeks
      and increased again during relapse. IFN-gamma mRNA stayed at control levels
      initially, but increased dramatically in the second weeks of chronic inflammation
      as well as in relapse. The mRNA levels of adhesion molecules, ICAM-1, VCAM-1, the
      mucosal homing integrin beta7 as well as P- and E-selectin were greatly enhanced
      between 1 and 3 weeks. The data showed that the chronically inflamed tissue
      expresses a time-dependent changing pattern of TH1 cytokines and adhesion
      molecules that maintain the infiltration and activation of inflammatory cells and
      tissue injury.

PMID- 11293665
TI  - Co-cultured human mast cells stimulate fibroblast-mediated contraction of
      collagen gels.
AB  - In the current study, we asked whether mast cells might modulate remodeling of
      extracellular matrix by affecting fibroblast-mediated contraction of three
      dimensional collagen gels. Mast cells and human lung fibroblasts were co-cultured
      in floating type I collagen gels. The area of the gels was measured by an image
      analyzer. Mast cells in co-culture augmented fibroblast contractility (P < 0.001)
      in a time- and concentration dependent manner. The tryptase inhibitor bis(5
      amidino-2-benzimidazo-lyl)methane (BABIM) were unable to block the augmented
      fibroblast contractility induced by co-cultured mast cells and tryptase added
      alone in the culture system had no effect on contractility, suggesting that other
      mediators besides tryptase might be involved. The amount of collagen in dissolved
      gels, measured as hydroxyproline, did not change after co-culture indicating that
      degradation of collagen may not be a major mechanism. Our findings support the
      hypothesis that the activity of mast cells may drive rearrangement of
      extracellular matrix and this and could subsequently lead to fibrosis and tissue
      dysfunction.

PMID- 11293666
TI  - Decreased leukotriene release from neutrophils after severe trauma: role of
      immature cells.
AB  - Polymorphonuclear granulocytes (PMN) play a key role in host defense against
      microbial infections. After severe trauma PMN show cellular dysfunctions
      including chemotactic migration, phagocytosis, and bacterial killing. In these
      settings the contribution of the cellular maturation stage compared to functional
      activities has not been investigated. Polymorphonuclear granulocytes are potent
      producers of lipid mediators via the 5-lipoxygenase (5-LO) pathway (leukotrienes,
      LTs) which exert important proinflammatory and immunoregulatory activities. We
      analyzed leukotriene generation from PMN-fractions (N = 23) of 15 polytrauma
      patients in comparison to 17 healthy donor cell fractions and correlated this
      lipid mediator release to the hematopoietic maturation stage of respective PMN.
      Polymorphonuclear granulocytes were isolated from EDTA-anticoagulated peripheral
      blood employing a one step procedure based on a discontinuous double Ficoll
      gradient. Cells (5 x 10(6)/500 microl phosphate-buffered saline) were stimulated
      for 20 min at 37 degrees C with 1 microM Ca-ionophor A23187 in the presence of 1
      mM Ca++ and 0.5 mM Mg++. Leukotrienes were analyzed by reversed-phase HPLC.
      Expression of 5-lipoxygenase (5-LO) was additionally determined by Western blot.
      Maturation stage of PMN was quantitated by Pappenheim-staining of cell smears.
      After polytrauma the generation of leukotrienes from PMN was individually
      diminished. Synthesis of enzymatically formed metabolites (LTB4, OH-LTB4 and COOH
      LTB4) was concomitantly reduced. The decresaed leukotriene synthesis strongly
      correlated (r2 = 0.907, P < 0.0001) to the occurrence of immature PMN (mostly
      band cells). The expression of 5-lipoxygenase in PMN fractions consisting mainly
      of band cells was decreased. Our results provide evidence that posttraumatic
      granulocyte dysfunction is partly due to immature functional cell capacities.

PMID- 11293668
TI  - Enzyme immunoassay for urogenital trichomoniasis as a marker of unsafe sexual
      behaviour.
AB  - Enzyme immunoassay (EIA) was used to detect antibodies to Trichomonas vaginalis
      in sera from Zimbabwe. The EIA showed a sensitivity of 95 and 94% when compared
      with vaginal swab culture among women attending a family planning clinic (FPC)
      and female commercial sex workers (CSW) respectively. The specificity was 85 and
      77% in the two groups. Culture-negative FPC women were sub-divided into high risk
      or low risk of exposure to trichomoniasis. The seroprevalence was 10% (6/61)
      among low risk women, 21% (10/48) among high risk women and 23% (9/39) among
      culture negative CSW. The EIA was positive in 46% (18/39) men with genital
      discharge but only 5% (2/37) healthy blood donors. None of 31 sera from
      prepubescent children was positive. The EIA may be useful for community surveys
      of trichomoniasis. Because T. vaginalis is a common sexually transmitted disease,
      the test may indicate behaviour that increases the risk of STD transmission.

PMID- 11293667
TI  - Differential activation of signal transduction pathways mediating phagocytosis,
      oxidative burst, and degranulation by chicken heterophils in response to
      stimulation with opsonized Salmonella enteritidis.
AB  - The activation of signal transduction pathways is required for the expression of
      functional enhancement of cellular activities. In the present studies, initial
      attempts were made to identify the signal transduction factors involved in
      activating phagocytosis, generation of an oxidative burst, and degranulation by
      heterophils isolated from neonatal chickens in response to opsonized Salmonella
      enteritidis (opsonized SE). Peripheral blood heterophils were isolated and
      exposed to known inhibitors of signal transduction pathways for either 20 min
      (staurosporin, genistein, or verapamil) or 120 min (pertussis toxin) at 39
      degrees C. The cells were then stimulated for 30 min at 39 degrees C with
      opsonized SE. Phagocytosis, luminol-dependent chemoluminescence (LDCL), and beta
      D glucuronidase release were then evaluated in vitro. The G-protein inhibitor
      pertussin toxin markedly inhibited (>80%) phagocytosis of opsonized SE. Both the
      protein kinase inhibitor (staurosporin) and calcium channel inhibitor (verapamil)
      reduced phagocytosis in a dose response manner. Genistein, a tyrosine kinase
      inhibitor, had no effect on phagocytosis. Staurosporin had a marked inhibitory
      effect on LDCL (>90%) while genistein had a dose responsive inhibition on LDCL.
      Both verapamil (40-45%) and pertussin toxin (50-55%) had a statistically
      significant, but less biologically significant effect on LDCL. Genistein
      significantly reduced the degranulation (78-81%) of heterophils by opsonized SE.
      Staurosporin also reduced degranulation by 43-50%, but neither verapamil nor
      pertussis toxin had a significant effect on degranulation. These findings
      demonstrate that distinct signal transduction pathways differentially regulate
      the stimulation of the functional activities of avian heterophils. Pertussin
      toxin-sensitive, Ca++-dependent G-proteins appear to regulate phagocytosis of
      opsonized SE, protein kinase C-dependent, tyrosine kinase-dependent protein
      phosphorylation plays a major role in LDCL, and tyrosine kinase(s)-dependent
      phosphorylation regulates primary granule release.

PMID- 11293670
TI  - Trypanosoma evansi in Indonesian buffaloes: evaluation of simple models of
      natural immunity to infection.
AB  - Deterministic models were employed to investigate the biology of Trypanosoma
      evansi infection in the Indonesian buffalo. Models were fitted to two age
      structured data sets of infection. The Susceptible-Infected-Susceptible (SIS)
      model was the best supported description of this infection, although the results
      of the analysis depended on the serological test used; the Tr7 Ag-ELISA was
      judged the most reliable indicator of infection. Estimated forces of infection
      increase with age from 1.2 to 2.0 acquisitions per buffalo per year. The
      buffaloes would clear infection in an estimated mean time period of 16.8 months
      (95% CIs: 12.5-25.9 months) since acquisition, either by drug treatment by owners
      or self-cure. A general discussion on the role of immunity in protozoan
      infections includes consideration that the fitted SIS model would be consistent
      with strain-specific immunity. The model may become a useful tool for the
      evaluation of control programmes.

PMID- 11293669
TI  - P fimbriae, capsule and aerobactin characterize colonic resident Escherichia
      coli.
AB  - Resident and transient Escherichia coli strains from the colonic microflora of 13
      Swedish schoolgirls were analysed for carriage of genes encoding a range of
      adhesins (P, type 1 and S fimbriae, Dr haemagglutinin and three varieties of the
      P fimbrial papG adhesin) and other virulence traits (K1 and K5 capsule,
      haemolysin and aerobactin) using multiplex PCR. Forty-four percent of the
      resident clones carried genes for P fimbriae, K1 or K5 capsule, and aerobactin,
      compared with only 3% of transient clones (P < 0.0001). The P-fimbriated clones
      most often had the class II variety of the P-fimbrial adhesin gene papG and this
      adhesin was significantly associated with persistence of a strain. S fimbriae and
      type 1 fimbriae were equally common in resident and transient strains. The
      results indicate that not only P fimbriae, but also, certain capsules and the
      ability to produce the siderophore aerobactin might contribute to persistence of
      E. coli in the large intestine.

PMID- 11293671
TI  - An analysis of a presumed major outbreak of pseudorabies virus in a vaccinated
      sow herd.
AB  - We describe a major outbreak of pseudorabies virus (PRV) in a sow herd in which
      the sows were vaccinated simultaneously three times a year with a vaccine
      containing Bartha strain. Also in the associated rearing herd in which the gilts
      were vaccinated twice an outbreak of PRV occurred. The outbreak was analysed with
      mathematical models, statistical methods and Monte-Carlo simulation. Under the
      assumption that the outbreak started with one introduction of virus the
      reproduction ratio R(ind)--as a measure of transmission of PRV between
      individuals--in the sow herd was estimated with a Generalized Linear Model to be
      1.6. Also under the assumption of one introduction of virus R(ind) in the rearing
      herd was estimated with a martingale estimator to be 1.7. Both estimates were
      significantly larger than 1. Mathematical analysis showed that heterogeneity in
      the sow herd, because of the presence of not-optimally immunized replacement sows
      could not be the only cause of the observed outbreak in the sow herd. With Monte
      Carlo simulations, the duration of an outbreak after a single introduction of
      virus and R(ind) = 1.6 did not mimic the data and thus the hypothesis of a single
      introduction with R(ind) = 1.6 could also be rejected and R(ind) is thus, not
      necessarily above 1. Moreover, with statistical analysis, endemicity in the
      combination of herds as a cause for the observed outbreak could be rejected.
      Endemicity in the rearing herd alone could not be excluded. Therefore, multiple
      introductions from outside and most probably from the rearing herd were possibly
      the cause of the observed outbreak(s). The implications for eradication of
      pseudorabies virus were discussed.

PMID- 11293672
TI  - Survival of Shiga toxin-producing Escherichia coli O157 in marine water and
      frequent detection of the Shiga toxin gene in marine water samples from an
      estuary port.
AB  - Shiga toxin-producing Escherichia coli (STEC) O157 was investigated with respect
      to its halotolerance and whether it can survive in marine water. STEC O157 could
      multiply in a medium containing 5% NaCl and in sterilized marine water, and could
      survive in unsterilized marine water for at least 15 days. On the basis of these
      results, we postulated that STEC O157 may survive in natural marine water, and
      attempted to isolate the bacterium and Shiga toxin gene (stx) from marine water
      in Japan. The stx, comprising stx1 and stx2, was detected from marine water
      samples by PCR. STEC and other stx-positive bacteria, however, could not be
      isolated from these samples in this study. These results indicate that stx
      positive bacteria may survive in marine water and suggest the necessity of a
      survey.

PMID- 11293673
TI  - An outbreak of E. coli O157 infection with evidence of spread from animals to man
      through contamination of a private water supply.
AB  - An outbreak of E. coli O157 infection occurred in the Highland Region of Scotland
      in the summer of 1999. The source of the outbreak was traced to an untreated
      private water supply. All six cases identified arose in visitors to the area, and
      most had very limited exposure to the contaminated water. Permanent residents on
      the same supply were unaffected. The E. coli O157 isolates from the water, sheep
      faeces collected from around the source and the human stool samples were
      indistinguishable using pulsed field gel electrophoresis. Previously reported
      outbreaks of E. coli O157 linked to potable water supplies have resulted from
      structural or treatment failures, which allowed faecal contamination of source
      water. Here, contamination of the water supply and subsequent human infection was
      due to the use of an untreated, unprotected private water source in a rural area
      where animals grazed freely.

PMID- 11293674
TI  - Selection bias in epidemiological studies of infectious disease using Escherichia
      coli and avian cellulitis as an example.
AB  - In epidemiological studies of infectious disease, researchers often rely on
      specific cues of the host, such as clinical signs, as surrogate indicators of
      pathogen presence. A selection bias would manifest if the specific visual cues
      used in sampling for the pathogen were not representative of the full range of
      signs caused by the strains of that pathogen. In our molecular epidemiological
      studies of Escherichia coli associated with avian cellulitis in broilers, we
      collect carcasses at the processing plant based on visual cues of lesion
      morphology. Therefore, the objectives of this study were to: (1) explore the
      potential impacts of selection bias in an application of infectious disease
      epidemiology, and (2) utilize a validation protocol to assess the potential for
      selection bias in our molecular epidemiological studies of E. coli and avian
      cellulitis. In two different trials, E. coli DNA fingerprints were compared
      between birds that our observers collected and the birds that the observers
      missed. Using Fisher's exact tests and simulation models, we determined that the
      isolates collected by the observers were not significantly different from the
      isolates missed by the observers (P > 0.60 in both trials). Our method of
      selecting birds suspected of having cellulitis did not significantly bias our
      inferences about the population of E. coli associated with cellulitis in the
      flock. We encourage more investigators to critically assess the relationship of
      the sample to the target population in epidemiological studies of infectious
      disease.

PMID- 11293675
TI  - Presence of Legionellaceae in warm water supplies and typing of strains by
      polymerase chain reaction.
AB  - Outbreaks of Legionnaire's disease present a public health challenge especially
      because fatal outcomes still remain frequent. The aim of this study was to
      describe the abundance and epidemiology of Legionellaceae in the human-made
      environment. Water was sampled from hot-water taps in private and public
      buildings across the area of Gottingen, Germany, including distant suburbs.
      Following isolation, we used polymerase chain reaction in order to generate
      strain specific banding profiles of legionella isolates. In total, 70 buildings
      were examined. Of these 18 (26%) had the bacterium in at least one water sample.
      Legionella pneumophila serogroups 1, 4, 5 and 6 could be identified in the water
      samples. Most of the buildings were colonized solely by one distinct strain, as
      proven by PCR. In three cases equal patterns were found in separate buildings.
      There were two buildings in this study where isolates with different serogroups
      were found at the same time.

PMID- 11293676
TI  - Serological survey of parapoxvirus infection in wild ruminants in Japan in 1996
      9.
AB  - The prevalence of parapoxvirus infection was examined in free-ranging wild
      ruminants in Japan, Japanese serow (Capricornis crispus) and Japanese deer
      (Cervus nippon centralis), in 1996-9. We collected a total of 151 serum samples
      from 101 Japanese serows and 50 Japanese deer and tested for antibodies against
      parapoxvirus by an enzyme-linked immunosorbent assay and an agar gel
      immunodiffusion test. Overall seroprevalences among Japanese serows were 5/25
      (20.0%) in 1996, 4/14 (28.6%) in 1997, 5/32 (15.6%) in 1998 and 2/30 (6.7%) in
      1999, respectively. The seroprevalence increased with age but was not affected by
      sex. No antibodies were detected from any of 50 serum samples taken from Japanese
      deer. Our results in this study suggest that parapoxvirus infection is widespread
      among the population of Japanese serows, however, Japanese deer appear to be
      still free of the disease.

PMID- 11293677
TI  - P fimbriae and aerobactin as intestinal colonization factors for Escherichia coli
      in Pakistani infants.
AB  - The carriage rate of a range of virulence genes was compared between resident and
      transient Escherichia coli strains obtained from the rectal flora of 22 home
      delivered Pakistani infants 0-6 months old. Genes for the following virulence
      factors were assessed using multiplex PCR: P, type 1 and S fimbriae, three P
      fimbrial adhesin varieties, Dr haemagglutinin, K1 and K5 capsule, haemolysin and
      aerobactin. The E. coli strains examined here differed from those previously
      obtained from hosts in Western Europe in a lower prevalence of genes for P, S and
      type 1 fimbriae, K1 capsule and haemolysin. Nevertheless, genes for P fimbriae,
      the class II variety of papG adhesin, and aerobactin were significantly more
      common among resident than transient strains, as previously observed in a Swedish
      study. The results suggest that P fimbriae and aerobactin, previously implicated
      as virulence factors for urinary tract infection, might contribute to persistence
      of E. coli in the normal intestinal microflora.

PMID- 11293678
TI  - Molecular epidemiology of multiple drug resistant type 6B Streptococcus
      pneumoniae in the Northern Territory and Queensland, Australia.
AB  - The emergence of type 6B Streptococcus pneumoniae resistant to five antibiotics
      (penicillin, chloramphenicol, trimethoprim sulphamethoxazole, erythromycin and
      tetracycline) in both the Northern Territory and Queensland prompted an
      investigation of the genetic relatedness and patterns of migration of the
      isolates. Pulsed field gel electrophoresis of genomic DNA of 74 multiple drug
      resistant (MDR) isolates cultured in both regions between August 1988 and June
      1997 showed that 100% of MDR isolates from the Northern Territory and 96% of MDR
      strains from Queensland were genetically indistinguishable or closely related to
      the index strain. None of a further 65 type 6B isolates that were resistant to
      one or two, or susceptible to all of the above antibiotics, were clonally related
      to the MDR pneumococci. The geographical distribution of the MDR type 6B clone
      increased over time. The index strain, first isolated in Darwin in August 1988,
      was identified in Brisbane, 2900 km distant, less than 4 years later and
      subsequently in other Queensland centres. Surveillance programmes are important
      to monitor the emergence and spread of potentially invasive MDR pneumococcal
      clones in countries that are well serviced by air and road transport.

PMID- 11293679
TI  - Epidemiological studies of human and animal Salmonella typhimurium DT104 and
      DT104b isolates in Ireland.
AB  - A total of 122 human and animal Salmonella Typhimurium DT104 isolates and 6
      epidemiologically related DT104b isolates from human and animal products were
      analysed by pulsed-field gel electrophoresis (PFGE). Genomic DNA was subjected to
      macrorestriction with three enzymes, SpeI, SfiI and XbaI. A total of 14
      restriction fragment length polymorphism (RFLP) profiles were identified when the
      PFGE patterns from the three enzymes were combined. The majority of isolates
      (81.2%) exhibited the same RFLP profile. Six animal DT104 isolates, susceptible
      to enrofloxacin and resistant to naladixic acid, were identified from the
      antibiotic susceptibility test. Four of these isolates had a different PFGE
      profile from the common RFLP. In addition, 4 of the 6 isolates were
      geographically clustered in one region. It was concluded that there was one
      predominant strain of S. Typhimurium DT104 in Ireland and that the potential and
      selection pressures for emergence of fluoroquinolone-resistant isolates were
      present.

PMID- 11293680
TI  - The effectiveness of Haemophilus influenzae type b conjugate vaccines in a high
      risk population measured using immunization register data.
AB  - The Northern Territory of Australia has had historically very high incidence
      rates of invasive Haemophilus influenzae type b disease in children less than 5
      years of age, with the burden of disease greatest among Aboriginal infants less
      than 12 months. This study documents the impact of conjugate Hib vaccines
      introduced in 1993. Immunization rates were monitored using an existing
      immunization register, and case finding was done retrospectively using hospital
      and laboratory records. Following the vaccine introduction, the incidence fell
      abruptly to a seventh of its pre-vaccination level, in both Aboriginal and non
      Aboriginal children. The effectiveness of PRP-OMPC (PedvaxHIB) was 97.5% and the
      overall effectiveness of the vaccination programme was 86.3%. The study shows Hib
      immunization as an effective intervention while discussing continuing needs for
      Hib control in high risk populations. It also illustrates the benefit of
      immunization registers in the evaluation of immunization programmes and
      assessment of vaccine effectiveness.

PMID- 11293681
TI  - Decreasing prevalence of helicobacter antibodies in Finland, with reference to
      the decreasing incidence of gastric cancer.
AB  - Time trends and geographical variation of Helicobacter pylori antibodies in
      Finland were investigated by enzyme immunoassay in 20- to 34-year-old randomly
      selected females from six localities during 1969-73 (n = 375), and 15- to 45-year
      old females representing nine communities and four geographical areas in 1983 (n
      = 882) and 1995 (n = 842). In the six communities investigated at three different
      time points, the overall prevalence declined from 38 to 12%, with an emphasis on
      the latter 12 years. The regionally varying rate of decrease in helicobacter
      prevalence changed the pre-existing geographical variation, leaving northern
      Finland with the highest rate. A 10%-units higher local helicobacter prevalence
      seemed to predict a 23% (95% CI 3-44%) higher gastric cancer incidence 20 years
      later. The overall decline in helicobacter seropositivity is consistent with
      earlier reports from Finland and other developed countries, and supports the
      cohort theory as an explanation for the age-related increase in H. pylori
      seroprevalence.

PMID- 11293682
TI  - The effect of age and study duration on the relationship between 'clustering' of
      DNA fingerprint patterns and the proportion of tuberculosis disease attributable
      to recent transmission.
AB  - Though it is recognized that the extent of 'clustering' of isolates from
      tuberculosis cases in a given population is related to the amount of disease
      attributable to recent transmission, the relationship between the two statistics
      is poorly understood. Given age-dependent risks of disease and the fact that a
      long study (e.g. spanning several years) is more likely to identify transmission
      linked cases than a shorter study, both measures, and thus the relationship
      between them, probably depend strongly on the ages of the cases ascertained and
      study duration. The contribution of these factors is explored in this paper using
      an age-structured model which describes the introduction and transmission of M.
      tuberculosis strains with different DNA fingerprint patterns in The Netherlands
      during this century, assuming that the number of individuals contacted by each
      case varies between cases and that DNA fingerprint patterns change over time
      through random mutations, as observed in several studies. Model predictions of
      clustering in different age groups and over different time periods between 1993
      and 1997 compare well against those observed. According to the model, the
      proportion of young cases with onset in a given time period who were 'clustered'
      underestimated the proportion of disease attributable to recent transmission in
      this age group (by up to 25% in males); for older individuals, clustering
      overestimated this proportion. These under- and overestimates decreased and
      increased respectively as the time period over which the cases were ascertained
      increased. These results have important implications for the interpretation of
      estimates of the proportion of disease attributable to recent transmission, based
      on 'clustering' statistics, as are being derived from studies of the molecular
      epidemiology of tuberculosis in many populations.

PMID- 11293684
TI  - Excess hospital admissions for pneumonia and influenza in persons > or = 65 years
      associated with influenza epidemics in three English health districts: 1987-95.
AB  - OBJECTIVES: To study the association between community influenza activity and
      acute hospital admissions for pneumonia and influenza among elderly persons.
      DESIGN: Multiple regression analysis of acute hospital admissions against
      community influenza activity, air temperature and seasonal and long-term trends.
      SETTING: Three English health districts: 1987-95. SUBJECTS: Persons aged > or =
      65 years. OUTCOME MEASURES: Acute hospital admissions for pneumonia and influenza
      (ICD9: 480-487); excess hospital admissions during epidemic periods. RESULTS: The
      final regression model explained 70% of the total variation in hospital
      admissions for pneumonia and influenza, including 14% due to community influenza
      activity. However, most variation was explained by long-term and seasonal changes
      unrelated to influenza. In the large influenza epidemic of 1989/90 a typical
      health district (500,000 total population) experienced 56 excess admissions for
      pneumonia and influenza attributable to epidemic influenza among persons aged >
      or = 65 years, requiring 672 additional bed-days. However the figure varied
      widely between seasons and over the whole study period, the average winter excess
      was 17.5 admissions per health district, requiring an additional 210 bed-days.
      CONCLUSIONS: Influenza epidemics exert a variable impact on acute hospital
      admissions for pneumonia and influenza among elderly persons, which in the past
      have been poorly quantified. Although the absolute numbers of excess admissions
      is modest, their impact on bed availability may be considerable because of the
      duration of hospital stay in elderly persons.

PMID- 11293683
TI  - A study of infectious intestinal disease in England: risk factors associated with
      group A rotavirus in children.
AB  - OBJECTIVE: To identify risk factors for infectious intestinal disease (IID) due
      to rotavirus group A in children aged under 16 years. METHODS: Case-control study
      of cases of IID with rotavirus infection presenting to general practitioners
      (GPs) or occurring in community cohorts, and matched controls. RESULTS: There
      were 139 matched pairs. In children under 16 years the following risk factors
      were significantly associated with rotavirus IID: living in rented council
      housing (adjusted OR = 3.78, P = 0.022), accommodation with more than five rooms
      (OR = 0.72, P = 0.002), contact with someone ill with IID (OR = 3.45, P < 0.001).
      Some foods were associated with decreased risk. In infants, bottle feeding with
      or without breast feeding was associated with increased risk (OR = 9.06, P <
      0.05). CONCLUSIONS: Contact with persons with IID, living in rented council
      housing and accommodation with fewer rooms, were significant risk factors for
      sporadic rotavirus IID in children whereas breast feeding is protective in
      infants.

PMID- 11293685
TI  - Analysis of Japanese encephalitis epidemic in Western Nepal in 1997.
AB  - We conducted an epidemiological study of a Japanese encephalitis (JE) outbreak in
      the southwestern part of Nepal in 1997. A high density of JE infections was found
      and it was estimated that 27.9% the total population were infected with JE virus
      in the study area. The fatality rate was 13.2% and there was no difference in the
      fatality rate between males and females over 5 years old. However, the case
      fatality rate was 2.1 times higher in females than in males (14.6% vs. 6.9%)
      among children under 5 years of age. Fifty-three blood samples were collected
      from suspected JE cases during the epidemic period in 1998. Findings for JE
      specific IgM revealed that clinical diagnoses of JE were serologically confirmed
      in an average 78% (70-93%) of patients in three collaborating hospitals. These
      studies demonstrated that JE was highly prevalent in the area and clinical
      diagnoses were reliable. Effective preventive measures should be taken against
      this vaccine-preventable disease.

PMID- 11293686
TI  - Death rates and causes of death in cohorts of serum hepatitis patients followed
      up for more than 20 years.
AB  - A cohort of 214 drug addicts with serum hepatitis and a cohort of 193 hepatitis
      patients without drug addiction were examined in respect of death rates, causes
      of death and a number of risk factors for reduced survival. The death rate was
      significantly higher among the drug addicts than among non-addicts. The annual
      mortality rate was 1.5% in the drug addict group and 0.7% in the non-addict
      group. The highest relative risk of death was 860 for female drug addicts in age
      group 15-24 compared to females of the same age in the general population. The
      most prevalent cause of death in the drug addict group was drug overdose (53%),
      whereas in the other group 66% died from various somatic diseases. Hepatitis or
      complications of viral hepatitis played no role as cause of death among the drug
      addicts, and infections as a whole were also responsible for very few deaths. For
      male drug addicts, imprisonment before admission and leaving hospital without the
      doctors' permission were risk factors for early death.

PMID- 11293687
TI  - Prevalence of antibodies to hepatitis C virus, HIV and human T-cell
      leukaemia/lymphoma viruses in injecting drug users in Tayside, Scotland, 1993-7.
AB  - The prevalence of blood-borne viruses in injecting drug users (IDUs) in Tayside,
      Scotland was determined by testing serum samples from IDUs who underwent
      attributable HIV antibody testing during 1993-7. The prevalence of antibodies to
      HIV was 29/802, (3.6%); to hepatitis C virus (HCV) 451/691, (65.3%); and to human
      T-cell leukaemia/lymphoma viruses type 1 and 2 (HTLV) 0/679, (0.0%). The
      prevalence of HIV and HCV antibodies were higher in subjects over the age of 25
      (P = 0.03 and P = 0.001, respectively). During 1993-7 the prevalence of HCV fell
      only in younger female IDUs (P < 0.01). HIV prevalence has declined dramatically
      since 1985, when a rate of 40% was recorded in similar populations. Harm
      reduction measures have failed to control HCV the spread of infection among IDUs
      in Tayside, as indicated by the high proportion of antibody positive IDUs,
      particularly males under the age of 25. Future studies should address the nature
      and effective reduction of continuing risk taking among IDUs in Tayside.

PMID- 11293688
TI  - Three-dimensional modeling for functional analysis of cardiac images: a review.
AB  - Three-dimensional (3-D) imaging of the heart is a rapidly developing area of
      research in medical imaging. Advances in hardware and methods for fast spatio
      temporal cardiac imaging are extending the frontiers of clinical diagnosis and
      research on cardiovascular diseases. In the last few years, many approaches have
      been proposed to analyze images and extract parameters of cardiac shape and
      function from a variety of cardiac imaging modalities. In particular, techniques
      based on spatio-temporal geometric models have received considerable attention.
      This paper surveys the literature of two decades of research on cardiac modeling.
      The contribution of the paper is three-fold: 1) to serve as a tutorial of the
      field for both clinicians and technologists, 2) to provide an extensive account
      of modeling techniques in a comprehensive and systematic manner, and 3) to
      critically review these approaches in terms of their performance and degree of
      clinical evaluation with respect to the final goal of cardiac functional
      analysis. From this review it is concluded that whereas 3-D model-based
      approaches have the capability to improve the diagnostic value of cardiac images,
      issues as robustness, 3-D interaction, computational complexity and clinical
      validation still require significant attention.

PMID- 11293689
TI  - A signal estimation approach to functional MRI.
AB  - In the last half decade, fast methods of magnetic resonance imaging have led to
      the possibility, for the first time, of non-invasive dynamic brain imaging. This
      has led to an explosion of work in the Neurosciences. From a signal processing
      viewpoint the problems are those of nonlinear spatio-temporal system
      identification. In this paper, we develop new methods of identification using
      novel spatial regularization. We also develop a new model comparison technique
      and use that to compare our method with existing techniques on some experimental
      data.

PMID- 11293690
TI  - An estimator for functional data with application to MRI.
AB  - We propose a method for restoring the underlying true signal in noisy functional
      images. The Nadaraya-Watson (NW) estimator described in, e.g., [1] is a classical
      nonparametric estimator for this problem. Since the true scene in many
      applications contains abrupt changes between pixels of different types, a
      modification of the NW estimator is needed. In the data we study, the
      characteristics of each pixel are given as a function of time. This means that a
      curve of data points is observed at each pixel. Utilizing this time information,
      the NW weights can be modified to obtain a weighted average over pixels with the
      same true value. Theoretical results showing the estimator's properties are
      developed. Several parameters play an important role for the restoration result.
      Practical guidelines are given for how these parameters can be selected. Finally,
      we demonstrate how the method can be successfully applied both to artificial data
      and Magnetic Resonance Images.

PMID- 11293691
TI  - Segmentation of brain MR images through a hidden Markov random field model and
      the expectation-maximization algorithm.
AB  - The finite mixture (FM) model is the most commonly used model for statistical
      segmentation of brain magnetic resonance (MR) images because of its simple
      mathematical form and the piecewise constant nature of ideal brain MR images.
      However, being a histogram-based model, the FM has an intrinsic limitation--no
      spatial information is taken into account. This causes the FM model to work only
      on well-defined images with low levels of noise; unfortunately, this is often not
      the the case due to artifacts such as partial volume effect and bias field
      distortion. Under these conditions, FM model-based methods produce unreliable
      results. In this paper, we propose a novel hidden Markov random field (HMRF)
      model, which is a stochastic process generated by a MRF whose state sequence
      cannot be observed directly but which can be indirectly estimated through
      observations. Mathematically, it can be shown that the FM model is a degenerate
      version of the HMRF model. The advantage of the HMRF model derives from the way
      in which the spatial information is encoded through the mutual influences of
      neighboring sites. Although MRF modeling has been employed in MR image
      segmentation by other researchers, most reported methods are limited to using MRF
      as a general prior in an FM model-based approach. To fit the HMRF model, an EM
      algorithm is used. We show that by incorporating both the HMRF model and the EM
      algorithm into a HMRF-EM framework, an accurate and robust segmentation can be
      achieved. More importantly, the HMRF-EM framework can easily be combined with
      other techniques. As an example, we show how the bias field correction algorithm
      of Guillemaud and Brady (1997) can be incorporated into this framework to achieve
      a three-dimensional fully automated approach for brain MR image segmentation.

PMID- 11293692
TI  - Three-dimensional multimodal brain warping using the demons algorithm and
      adaptive intensity corrections.
AB  - This paper presents an original method for three-dimensional elastic registration
      of multimodal images. We propose to make use of a scheme that iterates between
      correcting for intensity differences between images and performing standard
      monomodal registration. The core of our contribution resides in providing a
      method that finds the transformation that maps the intensities of one image to
      those of another. It makes the assumption that there are at most two functional
      dependencies between the intensities of structures present in the images to
      register, and relies on robust estimation techniques to evaluate these functions.
      We provide results showing successful registration between several imaging
      modalities involving segmentations, T1 magnetic resonance (MR), T2 MR, proton
      density (PD) MR and computed tomography (CT). We also argue that our intensity
      modeling may be more appropriate than mutual information (MI) in the context of
      evaluating high-dimensional deformations, as it puts more constraints on the
      parameters to be estimated and, thus, permits a better search of the parameter
      space.

PMID- 11293693
TI  - Automated manifold surgery: constructing geometrically accurate and topologically
      correct models of the human cerebral cortex.
AB  - Highly accurate surface models of the cerebral cortex are becoming increasingly
      important as tools in the investigation of the functional organization of the
      human brain. The construction of such models is difficult using current
      neuroimaging technology due to the high degree of cortical folding. Even single
      voxel misclassifications can result in erroneous connections being created
      between adjacent banks of a sulcus, resulting in a topologically inaccurate
      model. These topological defects cause the cortical model to no longer be
      homeomorphic to a sheet, preventing the accurate inflation, flattening, or
      spherical morphing of the reconstructed cortex. Surface deformation techniques
      can guarantee the topological correctness of a model, but are time-consuming and
      may result in geometrically inaccurate models. In order to address this need we
      have developed a technique for taking a model of the cortex, detecting and fixing
      the topological defects while leaving that majority of the model intact,
      resulting in a surface that is both geometrically accurate and topologically
      correct.

PMID- 11293694
TI  - Capillary electrophoresis as a tool for optimization of multiplex PCR reactions.
AB  - Copying multiple regions of a DNA molecule is routinely performed today using the
      polymerase chain reaction (PCR) in a process commonly referred to as multiplex
      PCR. The development of a multiplex PCR reaction involves designing primer sets
      and examining various combinations of those primer sets and different reaction
      components and/or thermal cycling conditions. The process of optimizing a
      multiplex PCR reaction in order to obtain a well-balanced set of amplicons can be
      time-consuming and labor-intensive. The rapid separation and quantitation
      capabilities of capillary electrophoresis make it an efficient technique to help
      in the multiplex PCR optimization process.

PMID- 11293695
TI  - Neurotransmitter sampling and storage for capillary electrophoresis analysis.
AB  - Quantitative analysis of signaling molecules from single cells and cellular
      materials requires careful validation of the analytical methods. Strategies have
      been investigated that enable single neurons and neuronal tissues to be stored
      before being assayed for many low-weight, biologically active molecules, such as
      serotonin, dopamine, and citrulline. Both metacerebral cell and pedal ganglia
      homogenates isolated from Pleiuohbrain-Chae californica have been studied by
      capillary electrophoresis with two complimentary laser-induced fluorescence
      detection methods. For homogenized ganglia samples, several cellular analytes
      (such as arginine and citrulline) are unaffected by standing at room temperature
      for days. Many other analytes in the biological matrix, including the
      catecholamines and indolamines, degrade by 20% within 10 h at room temperature.
      Rapidly freezing samples or preserving them with ascorbic acid preserves more
      than 80% of the dopamine and about 70% of the serotonin even after five days. In
      addition, serotonin and dopamine remain completely stable for at least five days
      by combining the ascorbic acid preservation and freezing at -20 degrees C. The
      timing of preservation is critical in maintaining the original composition of the
      biological samples. Using our optimum storage protocol of freezing the sample
      within 2 h after isolation, we can store frozen homogenate ganglia samples for
      more than four weeks before assay while still obtaining losses less than 10% of
      the original serotonin and dopamine. The nanoliter-volume single cell samples,
      however, must be analyzed within 4 h to obtain losses of less than 10% for
      serotonin related metabolites.

PMID- 11293696
TI  - Quantitative determination of clenbuterol, salbutamol and tulobuterol enantiomers
      by capillary electrophoresis.
AB  - Enantiomers of clenbuterol, salbutamol and tulobuterol were directly separated
      and quantitated from a spiked sample by capillary electrophoresis (CE) using
      sulfaited beta-cyclodextrin (SCD) as chiral selector and phosphate as running
      buffer. The SCD and buffer concentration, pH and field strength were the
      parameters studied to optimize the separation. Optimal separation was obtained
      using 50 mM of phosphate monobasic at pH = 2.24, 0.25% (w/w) of sulfated
      cyclodextrin and a field strength of 10 kV, with 20 min total time analysis.
      Comparison between two different injection modes (hydrodynamic and
      electrokinetic) was made. In the hydrodynamic mode, repeatability (expressed as
      relative standard deviation, RSD) was less than 1.2% for migration times for all
      the analyte peaks and less than 2% for peak area percentages. With respect to
      reproducibility, RSD was less than 3.8% for migration time and less than 3% for
      peak area percentages. Calibration curves were set up for two different sample
      concentration ranges (1 to 10 microg mL(-1) and 160-800 ng mL(-1), of each of the
      racemates studied). Although the electrokinetic injection mode for an aqueous
      sample appeared to suffer from some enantiodiscrimination, calibration curves
      were linear in the range between 1 and 10 ng mL(-1) with regression coefficients
      ranging from 0.9996 to 0.9952. As in the case of hydrodynamic injection, the
      method was tested with a spiked sample.

PMID- 11293697
TI  - Determination of enterostatin in human cerebrospinal fluid by capillary
      electrophoresis with laser induced fluorescence detection.
AB  - A capillary electrophoresis (CE) method with laser induced fluorescence (LIF)
      detection is described for quantification of enterostatin (Val-Pro-Asp-Pro-Arg),
      a pentapeptide involved in appetite regulation and insulin secretion.
      Enterostatin and two other pentapeptides belonging to the enterostatin family
      (i.e. Ala-Pro-Gly-Pro-Arg and Val-Pro-Gly-Pro-Arg) were well separated from each
      other. The peptides were fluorescently tagged with naphthalene-2,3-
      dicarboxaldehyde (NDA) and separated by micellar electrokinetic chromatography
      (MEKC) in the presence of methanol as an organic modifier. Coupled with LIF
      detection, the method had a detection limit of 4.8 x 10(-6) M for enterostatin.
      The relative standard deviation was to be 4.0% from five determinations of
      enterostatin at 37.2 microM in a human cerebrospinal fluid (CSF) sample. Twenty
      three human CSF samples were analyzed. The level of enterostatin ranged from 24
      microM to 51 microM with a mean (+/- SEM) value of 41.7 +/- 2.0 microM.

PMID- 11293698
TI  - Electrospray ionization gas-phase electrophoresis under ambient conditions and
      it's potential or high-speed separations.
AB  - A moderately high resolution nanoelectrospray ionization gas-phase
      electrophoresis instrument was constructed and evaluated for simple high-speed
      separations of several groups of compounds. The insertion of a plate containing a
      1.6 cm diameter exit orifice, 2.5 cm from the location of electrospray, allowed
      ions to be created and desolvated under ambient conditions with minimal solvent
      contamination to the drift tube. Ion separation selectivity is discussed and
      shown to be slightly altered by changing the drift gas flow rate. Issues of using
      gas-phase electrophoresis as a high-speed separation technique are discussed. Gas
      phase electrophoresis-spectra of selected benzodiazepines, triazine herbicides,
      and simple combinatorial chemistry libraries are demonstrated.

PMID- 11293699
TI  - Gas-phase separations of complex tryptic peptide mixtures.
AB  - High-resolution ion mobility and time-of-flight mass spectrometry techniques have
      been used to analyze complex mixtures of peptides generated from tryptic
      digestion of fourteen common proteins (albumin, bovine, dog, horse, pig, and
      sheep; aldolase, rabbit; beta-casein, bovine; cytochrome c, horse; beta
      lactoglobulin, bovine; myoglobin, horse; hemoglobin, human, pig, rabbit, and
      sheep). In this approach, ions are separated based on differences in mobilities
      in helium in a drift tube and on differences in their mass-to-charge ratios in a
      mass spectrometer. From data recorded for fourteen individual proteins (over a
      m/z range of 405 to 1,000), we observe 428 peaks, of which 205 are assigned to
      fragments that are expected from tryptic digestion. In a separate analysis, the
      fourteen mixtures have been combined and analyzed as one system. In the single
      dataset, we resolve 260 features and are able to assign 168 peaks to unique
      peptide sequences. Many other unresolved features are observed. Methods for
      assigning peptides based on the use of m/z information and existing mobilities or
      mobilities that are predicted by use of intrinsic size parameters are described.

PMID- 11293700
TI  - Detection of double-stranded PCR amplicons at the attomole level electrosprayed
      from low nanomolar solutions using FT-ICR mass spectrometry.
AB  - An 82-base-pair polymerase chain reaction (PCR) product was amplified from the
      tetranucleotide short tandem repeat locus within the human tyrosine hydroxylase
      gene. PCR amplification was carried out using 100 ng of human nuclear DNA
      obtained from an individual who is homozygotic for the 9.3 allele resulting in a
      50.5 kDa amplicon. To generate sufficient material for these investigations,
      several reactions were pooled and subsequently purified and quantified using UV
      vis spectrophotometry. A serial dilution was carried out from a 2 microM stock
      solution providing solution concentrations down to 5 nM. Measurements were made
      using hexapole accumulation and gated trapping strategies in a 4.7 Telsa Fourier
      transform ion cyclotron resonance mass spectrometer (FTICR-MS) which facilitated
      detection of the amplicon at the attomole level when electrosprayed from a 5 nM
      solution with a single acquisition! The signal-to-noise ratio was determined to
      be 8.3 for the spectrum derived from the 5 nM solution using the magnitude-mode
      mass spectral peak height for the most abundant charge-state. This remarkable
      sensitivity for large PCR amplicons will dramatically improve the ability of
      electrospray ionization mass spectrometry to address important genetic questions
      for low copy number genes or when the amount of initial template is limited; the
      latter issue is commonly encountered in DNA forensics. Furthermore, these data
      represents over 2 orders of magnitude decrease in detection limits over other
      existing ESI-MS reports concerning PCR products, including those conducted using
      FTICR-MS.

PMID- 11293701
TI  - Mapping tertiary interactions in protein folding reactions: a novel mass
      spectrometry- and chemical synthesis-based approach.
AB  - A novel mass spectrometry- and chemical synthesis-based approach for studying
      protein folding reactions is described, and its initial application to study the
      folding/unfolding reaction of a homo-hexameric enzyme 4-oxalocrotonate (4OT) is
      reported. This new approach involves the application of total chemical synthesis
      to prepare protein analogues that contain a photoreactive amino acid site
      specifically incorporated into their primary amino acid sequence. To this end, a
      photoreactive amino acid-containing analogue of 4OT in which Pro-1 was replaced
      with p-benzoyl-l-phenylalanine (Bpa) was prepared. This analogue can be used to
      map structurally specific protein-protein interactions in 4OT's native folded
      state. These photocrosslinking studies and peptide mapping results with
      (PlBpa)4OT indicate that this construct is potentially useful for probing the
      structural properties of equilibrium and kinetic intermediates in 4OT's folding
      reaction.

PMID- 11293702
TI  - Luminescent proteins from Aequorea victoria: applications in drug discovery and
      in high throughput analysis.
AB  - Recent progress in generating a vast number of drug targets through genomics and
      large compound libraries through combinatorial chemistry have stimulated
      advancements in drug discovery through the development of new high throughput
      screening (HTS) methods. Automation and HTS techniques are also highly desired in
      fields such as clinical diagnostics. Luminescence-based assays have emerged as an
      alternative to radiolabel-based assays in HTS as they approach the sensitivity of
      radioactive detection along with ease of operation, which makes them amenable to
      miniaturization. Luminescent proteins provide the advantage of reduced reagent
      and operating costs because they can be produced in unlimited amounts through the
      use of genetic engineering tools. In that regard, the use of two naturally
      occurring and recombinantly produced luminescent proteins from the jellyfish
      Aequorea victoria, namely, aequorin and the green fluorescent protein (GFP), has
      attracted attention in a number of analytical applications in diverse research
      areas. Aequorin is naturally bioluminescent and has therefore, virtually no
      associated background signal, which allows its detection down to attomole levels.
      GFP has become the reporter of choice in a variety of applications given that it
      is an autofluorescent protein that does not require addition of any co-factors
      for fluorescence emission. Furthermore, the generation of various mutants of GFP
      with differing luminescent and spectral properties has spurred additional
      interest in this protein. In this review, we focus on the use of aequorin and GFP
      in the development of highly sensitive assays that find applications in drug
      discovery and in high throughput analysis.

PMID- 11293703
TI  - Comparison of sieving matrices for on-the-fly fluorescence lifetime detection of
      dye-labeled DNA fragments.
AB  - Commercially available, replaceable sieving matrices and their solvent modulated
      forms were evaluated for use in on-the-fly fluorescence lifetime detection of dye
      labeled DNA fragments in capillary electrophoresis. The fragments were labeled
      with dyes that can be excited by the 488 nm line of an argon ion laser and have
      lifetimes in the range of 0.8 ns to 3.8 ns. The sieving matrices and buffer
      systems included poly(vinylpyrrolidone) (PVP), poly(ethyleneoxide) (PEO),
      hydroxyethylcellulose (HEC), Tris-borate-EDTA (TBE) and Tris-TAPS-EDTA buffers
      modified with DMSO and formamide. Selection of the optimal sieving matrix is
      based on the separation efficiency and the enhancement of lifetime resolution of
      DNA fragments. Best results for both electrophoretic resolution and lifetime
      detection were obtained using a poly(ethyleneoxide)/TBE gel buffer in the
      presence of 10% formamide.

PMID- 11293704
TI  - Development of a sensitive enzyme immunoassay for the detection of phenyl-beta-D
      thioglucuronide in human urine.
AB  - Immunoassays for the measurement of glucuronides in human urine can be a helpful
      tool for the assessment of human exposure to toxic chemicals. Therefore an enzyme
      imimunoassay (EIA) for the specific detection of phenyl-beta-D-thioglucuronide
      was developed. The immunoconjugate was formed by coupling p-aminophenyl-beta-D
      thioglucuronide to the carrier protein thyroglobulin leaving an exposed
      glucuronic acid. The hapten-protein conjugate was adsorbed to gold colloids in
      order to enhance the immunogenic effect. Rabbits were injected with the
      immunogold conjugates to raise polyclonal antibodies. The resulting competitive
      assay showed an inhibition by phenyl-beta-D-thioglucuronide at sample
      concentrations of 23.0 +/- 1.3 ng/mL (50% B/B0) and a high cross-reactivity to p
      aminophenyl-beta-D-thioglucuronide (120%). Little cross-reactivities (< 2%) were
      observed for potential urinary cross reactants. In addition human urine samples
      were incubated with beta-glucuronidase in order to investigate the EIA for
      specific matrix effects. An integration of high-performance liquid chromatography
      (HPLC) and EIA was developed in an attempt to decrease the matrix effects and
      increase the sensitivity of the overall method. The hyphenated technique HPLC-EIA
      may be used to monitor human exposure to toxic thiophenol which is excreted by
      mammals as urinary phenyl thioglucuronide.

PMID- 11293705
TI  - Improving the activity of immobilized subtilisin by site-directed attachment
      through a genetically engineered affinity tag.
AB  - An octapeptide affinity tag, Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys (temied FLAG), was
      genetically fused to the C-terminus of subtilisin BPN' (SBT) from Bacillus
      amyloliquefaciens. The fusion protein SBT-FLAG was immobilized to nonporous
      polystyrene and silica beads both in a site-directed and a random fashion. Site
      directed immobilization was achieved by employing the interaction between protein
      A and a monoclonal antibody specific for the FLAG peptide, while random
      immobilization was obtained by using glutaraldehyde as a cross-linking reagent.
      The activity of the immobilized enzymes was compared. It was found that the site
      directed subtilisin had higher catalytic efficiency, kcat/KM, which was more than
      7-fold of that of the randomly immobilized enzyme. It was also noted that the
      site-directly immobilized enzyme had superior storage stability over the
      homogeneous enzyme.

PMID- 11293706
TI  - Analytical performance characteristics of thin and thick film amperometric
      microcells.
AB  - The analytical performance of amperometric microcells with different electrode
      geometries is compared for enzyme activity measurements. The microcells were
      fabricated with thin film photolithography or thick film screen-printing in four
      different designs. The cells made with the thin film process used flexible
      substrate with microelectrode array or a circular, disk-shaped working electrode.
      The screen-printed working electrodes had semicircle or disk shape on ceramic
      chips. Putrescine oxidase (PUO) activity measurement was used as a model. The
      determination of PUO activity is important in the clinical diagnosis of premature
      rupture of the amniotic membrane. An electropolymerized m-phenylenediamine size
      exclusion layer was used to eliminate common interferences. The size exclusion
      layer revealed also to be advantageous in protecting the electrodes from fouling
      by putrescine (enzyme substrate). The electrode fouling of bare electrodes was
      insignificant for screen-printed electrodes, but very severe for electroplated
      platinum working electrodes. The microelectrode array electrodes demonstrated
      smaller RSD and higher normalized sensitivities for hydrogen peroxide and PUO
      activity. All the other electrodes were demonstrating comparable analytical
      performances.

PMID- 11293707
TI  - Detection of E. coli using a microfluidics-based antibody biochip detection
      system.
AB  - This work demonstrates the detection of E. coli using a 2-dimensional photosensor
      array biochip which is efficiently equipped with a microfluidics sample/reagent
      delivery system for on-chip monitoring of bioassays. The biochip features a 4 x 4
      array of independently operating photodiodes that are integrated along with
      amplifiers, discriminators and logic circuitry on a single platform. The
      microfluidics system includes a single 0.4 mL reaction chamber which houses a
      sampling platform that selectively captures detection probes from a sample
      through the use of immobilized bioreceptors. The independently operating
      photodiodes allow simultaneous monitoring of multiple samples. In this study the
      sampling platform is a cellulosic membrane that is exposed to E. coli organisms
      and subsequently analyzed using a sandwich immunoassay involving a Cy5-labeled
      antibody probe. The combined effectiveness of the integrated circuit (IC) biochip
      and the immunoassay is evaluated for assays performed both by conventional
      laboratory means followed by detection with the IC biochip, and through the use
      of the microfluidics system for on-chip detection. Highlights of the studies show
      that the biochip has a linear dynamic range of three orders of magnitude observed
      for conventional assays, and can detect 20 E. coli organisms. Selective detection
      of E. coli in a complex medium, milk diluent, is also reported for both off-chip
      and on-chip assays.

PMID- 11293708
TI  - Atomic force microscopy for the characterization of immobilized enzyme molecules
      on biosensor surfaces.
AB  - The development of biosensors has been one of the key areas in biotechnology and
      biomedical studies. Often it is difficult to investigate the immobilized
      biomolecules on the surfaces for biosensor optimization. Atomic force microscopy
      (AFM) should provide an ideal means for the visualization of biosensor surface
      and for the investigation of biomolecule activities. Therefore, AFM has been
      employed to study the surface topography of immobilized glutamate dehydrogenase
      (GDH) on two-dimensional glutamate biosensor surfaces. Correlation between the
      surface topography and the activity of the biosensor was investigated. Surface
      analysis has revealed that the enzymatic activity of the immobilized GDH
      molecules on the biosensor surface is linked to surface roughness, as measured by
      the peak-to-valley distance. Fractal dimension of the immobilization sensor
      surface was found to be a good parameter for judging the quality of the
      immobilized biosensors. As enzyme immobilization time increases, the biosensor
      has its maximum activity with around 18 h of immobilization in 10(-6) M GDH
      solution. Various biosensors prepared under different experimental conditions
      have been studied by AFM. This technique is shown to be an effective tool to
      characterize biosensor surfaces.

PMID- 11293709
TI  - Evaluation of NMR diffusion measurements for the conformational analysis of
      flexible peptides.
AB  - The use of diffusion coefficients measured with pulsed-field gradient NMR
      spectroscopy for the determination of the relative population of conformers in
      solutions of the human Growth Hormone peptide fragment, hGH(9-19), has been
      studied in aqueous and in trifluoroethanol (TFE)/ water solutions. The peptide is
      a good model compound for this study because it adopts a predominantly random
      coil conformation in aqueous solution and is helical in TFE. The results of the
      diffusion measurements suggest that the peptide exhibits predominantly random
      coil structures in aqueous solution and adopts a more helical conformation in
      solutions containing increasing mole fractions of TFE, consistent with the
      qualitative findings of the standard CD and NMR experiments to probe peptide
      conformation. These results indicate that diffusion coefficients measured with
      NMR can provide additional information about temperature- and solvent-induced
      changes in the extent of the helical conformer for hGH(9-19) in aqueous solution
      and in solutions containing various mole fraction of TFE, respectively.

PMID- 11293710
TI  - Development and analytical applications of multispectral imaging techniques: an
      overview.
AB  - A multispectral imaging spectrometer is an instrument that can simultaneously
      record spectral and spatial information of a sample. Chemical and physical
      properties of the sample can be elucidated from such images. By synergistic use
      of an acousto-optic tunable filter and a progressive scan camera capable of snap
      shot recording it was possible to develop a novel imaging spectrometer with a
      spatial resolution of a few microns and which can record, grab and store up to 33
      images per second (at a function of time) or 16 images per second (as a function
      of wavelength). This overview article summarizes the instrumentation development
      of various imaging spectrometers and their applications including its use as the
      detector for the determination of identity and sequences of peptides synthesized
      by the combinatorial solid phase method.

PMID- 11293711
TI  - LIBS using dual- and ultra-short laser pulses.
AB  - Pre-ablation dual-pulse LIBS enhancement data for copper, brass and steel using
      ns laser excitation are reported. Although large enhancements are observed for
      all samples, the magnitude of the enhancement is matrix dependent. Whereas all of
      the dual-pulse studies used ns laser excitation we see interesting effects when
      using ps and fs laser excitation for single-pulse LIBS. LIBS spectra of copper
      using 1.3 ps and 140 fs laser pulses show much lower background signals compared
      to ns pulse excitation. Also, the atomic emission decays much more rapidly with
      time. Because of relatively low backgrounds when using ps and fs pulses, non
      gated detection of LIBS is shown to be very effective. The plasma dissipates
      quickly enough using ps and fs laser pulses, that high pulse rates, up to 1,000
      Hz, are effective for increasing the LIBS signal, for a given measurement time.
      Finally, a simple near-collinear dual-pulse fiber-optic LIBS probe is shown to be
      useful for enhanced LIBS measurements.

PMID- 11293712
TI  - Vibrational spectroscopy of dimethylchlorooctadecylsilane covalently bonded to
      ultrathin silica films immobilized on Ag surfaces.
AB  - FTIR and Raman spectroscopies have been used to characterize the structure and
      conformational order of dimethylchlorooctadecylsilane (DOS) covalently bonded to
      ultrathin silica films supported on Ag substrates. Ultrathin silica films of ca.
      30 A thickness prepared from sol-gel methods are immobilized on Ag surfaces
      modified with a self-assembled monolayer of (3-mercaptopropyl)trimethoxysilane
      (3MPT). This layered structure provides a unique opportunity for acquiring
      complementary spectral data from both FTIR and Raman spectroscopies, which are
      useful in elucidating alkylsilane conformation pertaining to stationary phases
      for reversed-phase liquid chromatography (RPLC). Characterization of
      octadecyltrichlorosilane (OTS) layers on thin silica films of ca. 800 A thickness
      on 3MPT-modified Ag surfaces has been reported previously. Differences between
      the ultrathin silica films used in this study and the thin silica films used in
      this previous study are considered. The results from both FTIR and Raman
      spectroscopy presented here suggest that bonded DOS alkyl chains are in a
      disordered, liquid-like state with close to monolayer surface coverage.

PMID- 11293713
TI  - Characterization of isopoly tungstate using time-of-flight electrospray mass
      spectrometry.
AB  - Electrospray time-of-flight (TOF) mass spectrometry has been carried out on
      aqueous solutions of isopoly tungstate. A number of factors affecting the
      speciation of tungstate were studied, including concentration, and pH. The
      concentrations of the solutions ranged from 10(-2) to 10(-5) M. At all
      concentrations studied, the pH range was sufficient to investigate all major
      species expected to be in aqueous solution. In all cases, the results obtained by
      electrospray showed changes in speciation which were limited to protonation and
      solvation effects; the tungstate core remained intact.

PMID- 11293714
TI  - X-ray photoelectron spectroscopic studies of the oxidation of aluminium by liquid
      water monitored in an anaerobic cell.
AB  - The oxidation of clean polycrystalline aluminium foil was performed in a
      previously described anaerobic cell and studied by core level and valence band X
      ray photoelectron spectroscopy. Oxide free sample surfaces were exposed under
      inert atmosphere at room temperature to increasingly oxidative environments of
      water vapor and liquid water beginning with an oxide free metal foil each time.
      Minor oxidative environments were found to produce a film of boehmite with a
      thinner outer film of gibbsite. Harsher oxidation in liquid water resulted in an
      oxide film much thicker than that found on the as received sample which contained
      an inner composition of gamma alumina with an outer film of gibbsite. As
      expected, the oxide film observed for ultra high purity polycrystalline
      aluminiurm foil in the as received state was gibbsite. The valence band of the
      cleaned metal is discussed in terms of residual surface species. The evaluation
      and determination of these residual surface species is evaluated following an
      analysis of two different band structure calculations which use different d
      orbital exponents. It is found that while the density of states is almost
      unaltered by changes in the d exponent, the predicted spectrum is substantially
      changed. The work makes extensive use of valence band X-ray photoelectron
      spectroscopy.

PMID- 11293715
TI  - Spectral tolerance determination for multivariate optical element design.
AB  - Recent reports from our laboratory have described a method for all-optical
      multivariate chemometric prediction from optical spectroscopy. The concept behind
      this optical approach is that a spectral pattern (a regression vector) can be
      encoded into the spectrum of an optical filter. The key element of these
      measurement schemes is the multivariate optical element (MOE), a multiwavelength
      interference-based spectral discriminator that is tied to the regression vector
      of a particular measurement. The fabrication of these MOEs is a complex operation
      that requires precise techniques. However, to date, no quantitative means of
      determining the allowable design/ manufacturing errors for MOEs has existed. The
      purpose of the present report is to show how the spectroscopy of a sample is used
      to define the accuracy with which MOEs must be designed and manufactured. We
      conclude this report with a general treatment of spectral tolerance and a worked
      example. The worked example is based on actual experimental measurements. We show
      how the spectral bandpass is defined operationally in a real problem, and how the
      statistics of the theoretical regression vector influence both the bandpass and
      the minimum tolerances. In the experimental example, we demonstrate that
      tolerances range continuously between 1 (totally tolerant) to approximately 10(
      3) (0.1% T) in this problem.

PMID- 11293716
TI  - Determination of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in
      air particulate and marine sediment standard reference materials (SRMs).
AB  - Due to the limited number of environmental matrix certified reference materials
      (CRMs) with assigned values for natural levels of polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs), an interlaboratory study was undertaken by
      the National Institute of Standards and Technology (NIST) and Environment Canada
      to establish reference concentration values for selected PCDD/Fs in two well
      characterized NIST Standard Reference Materials (SRMs): SRM 1649a (Urban Dust)
      and SRM 1944 (New York/New Jersey Waterway Sediment). Results from 14
      laboratories were used to provide reference values for the seventeen 2, 3, 7, 8
      substituted PCDD/F congeners, the totals for individual tetra- through hepta
      substituted PCDD/F homologues, and the total amount of tetra- through hepta
      substituted PCDD/Fs. The mass fractions for the individual 2, 3, 7, 8-substituted
      congeners range from approximately 0.01 microg/kg to 7 microg/kg dry mass.

PMID- 11293717
TI  - Certification of the methylmercury content in SRM 2977 mussel tissue (organic
      contaminants and trace elements) and SRM 1566b oyster tissue.
AB  - The methylmercury content in two new marine bivalve mollusk tissue Standard
      Reference Materials (SRMs) has been certified using results of analyses from the
      National Institute of Standards and Technology (NIST) and two other laboratories.
      The certified concentrations of methylmercury were established based on the
      results from four and six different (independent) analytical methods,
      respectively, for SRM 1566b Oyster Tissue (13.2 +/- 0.7 microg/kg) and SRM 2977
      Mussel Tissue (organic contaminants and trace elements) (36.2 +/- 1.7 microg/kg).
      The certified concentration of methylmercury in SRM 1566b is among the lowest in
      any certified reference material (CRM).

PMID- 11293718
TI  - LC-MS/MS signal suppression effects in the analysis of pesticides in complex
      environmental matrices.
AB  - The application of LC separation and mobile phase additives in addressing LC
      MS/MS matrix signal suppression effects for the analysis of pesticides in a
      complex environmental matrix was investigated. It was shown that signal
      suppression is most significant for analytes eluting early in the LC-MS analysis.
      Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide,
      formic acid) into the LC mobile phase was effective in improving signal
      correlation between the matrix and standard samples. The signal improvement is
      dependent on buffer concentration as well as LC separation of the matrix
      components. The application of LC separation alone was not effective in
      addressing suppression effects when characterizing complex matrix samples.
      Overloading of the LC column by matrix components was found to significantly
      contribute to analyte-matrix co-elution and suppression of signal. This signal
      suppression effect can be efficiently compensated by 2D LC (LC-LC) separation
      techniques. The effectiveness of buffers and LC separation in improving signal
      correlation between standard and matrix samples is discussed.

PMID- 11293719
TI  - Spectrochemical investigations in molecularly organized solvent media: evaluation
      of pyridinium chloride as a selective fluorescence quenching agent of polycyclic
      aromatic hydrocarbons in aqueous carboxylate-terminated poly(amido) amine
      dendrimers and anionic micelles.
AB  - The ability of pyridinium chloride (PC) to selectively quench alternant as
      opposed to nonaltemant polycyclic aromatic hydrocarbons (PAHs) in organized media
      is examined. PC was previously shown to be a selective quenching agent of
      alternant PAHs in neat polar solvents. Carboxylate-terminated poly(amido) amine
      (PAMAM-CT) dendrimers and anionic surfactants--sodium dodecanoate (SD), sodium
      octanoate (SO), and sodium dodecylsulfate (SDS)--were chosen as the solubilizing
      media for this study. Selective quenching of alternant PAHs is observed in the
      presence of the SDS and SO micelles. However, the extent of PAH quenching in SO
      is significantly reduced compared to PAHs dissolved in either water or SDS
      micelles. In the case of the smaller generation 4.5 (G4.5) PAMAM-CT dendrimers,
      PC was prevented from quenching both alternant and nonalternant PAHs to any
      appreciable extent. The dendrimer is able to "protect" the PAHs from the PC
      quencher that resides at the dendrimer surface. Both, SD and G5.5 PAMAM-CT
      precipitated out of solution with the addition of PC. Differences between
      traditional micelles and "unimolecular micelle" dendrimers were also examined.
      These studies further confirm that the PAHs did not reside in the "analogous"
      palisade region of the dendrimers as they do in micelles. The PAHs must reside in
      the outermost branches of the dendrimer, but sufficiently far enough away from
      the charged surface groups, where PC associated, to prevent fluorescence
      quenching. This work further illustrates the differences between "unimolecular
      micelle" dendrimers and traditional micelles.

PMID- 11293720
TI  - Retention behavior of large polycyclic aromatic hydrocarbons on
      metalloprotoporphyrin-silica stationary phases.
AB  - The retention behavior of large polycyclic aromatic hydrocarbons (LPAHs) (> or =
      7 rings) on newly developed metalloplotoporphyrin (MProP)-silica stationary
      phases is examined and the results are compared to previously reported data for
      retention of the same solutes on commercially available phases. HPLC columns
      packed with FeProP-silica are shown to exhibit unique shape selectivity for LPAH
      retention, with the planar LPAHs always retained much longer than corresponding
      non-planar solutes. Solute planarity, length to breadth ratio (L/B value), and
      number of carbon atoms within the LPAHs are all demonstrated to contribute to the
      retention sequence observed. Further, the retention of LPAH solutes on FeProP
      silica phases is shown to be more predictable than on other reversed-phase
      columns, with the elution sequence constant regardless of the mobile phase
      composition. Due to the extremely high planar selectivity of FeProP-silicas with
      respect to LPAH retention, it is envisioned that columns packed with these phases
      could be used in conjunction with existing commercial columns to devise Inethods
      for more efficient separation of complex mixtures of LPAHs in environmental and
      other samples.

PMID- 11293721
TI  - Determination of energetic materials in soil using multivariate analysis of Raman
      spectra.
AB  - Contamination of soils by energetic materials (EMs) is an important issue in many
      locations (such as test mounds, ordnance depots, and manufacturing sites). Raman
      spectroscopy can be useful as a screening technique at the percent level (by
      mass) if interference from soil fluorescence can be overcome. Multivariate
      analysis is shown capable of both extracting the Raman signatures of EMs from
      spectra obscured by large fluorescence backgrounds caused by soil components, and
      generating calibration curves for the EMs at the percent level.

PMID- 11293723
TI  - Familial resemblance for the age at menarche in Basque population.
AB  - A cross-sectional sample from Biscay province (Basque Country, Spain) composed of
      296 subjects from 143 nuclear families was analysed. The aim of this research was
      to study familial resemblance for the age at menarche and to investigate the
      influence that BMI, fatness and several socio-familial variables have on the
      menarcheal age. The influence of these variables on the degree of similarity of
      mother-daughter and sister-sister pairs for the age at onset of menstruation will
      be determined. Mean ages at menarche of mothers estimated by retrospective
      methodology (12.88 years, SD = 1.57) and daughters assessed by probit analysis
      (12.34 years. SD= 1.00) showed no statistically significant differences. Mother
      daughter and sister-sister correlations increased after controlling for BMI,
      fatness and several socio-familial variables (0.25 vs 0.36 and 0.28 vs 0.44,
      respectively). The results revealed the importance of BMI, fatness, socio
      economic level and the number of people living together in the household on
      menarcheal age and on the estimation of correlations. However, no influence from
      sibship size (possibly because this variable is a part of the people living
      together in the household) nor from birth order of the subjects was observed.

PMID- 11293724
TI  - Marriage behaviour in the Alpine Non Valley from 1825 to 1923.
AB  - BACKGROUND: The study is part of a research project on the marital structure of
      mountain populations from the Eastern Italian Alps. Little is known about
      marriage patterns in this Alpine area. AIM: The aim of the study is to evaluate
      the extent of reproductive isolation in some communities of the Non Valley
      (Trentino, Italy) and to investigate its microgeographic and temporal changes
      over the period 1825-1923. SUBJECTS AND METHODS: 4518 microfilmed marriage
      records from registers of seven parishes of the Non Valley were used to analyse
      the following: endogamy rate, inbreeding calculated both from dispensations and
      from isonymy, repeating pairs of surnames in marriages, isonymic relationships.
      RESULTS: The results show notable variability among parishes in the levels of
      endogamy (40-73%), inbreeding (alpha: 1.9-4.57; Ft: 0.0073-0.019) and subdivision
      (RPr/RP: 0.5-1.3). The values are relatively stable over the course of a century,
      apart from a rise in inbreeding indicated by dispensations and a slight decrease
      of endogamy at the beginning of the 20th century. Isonymic relationships reflect
      geographic proximity between populations, with minimum changes through time.
      CONCLUSIONS: Variations in the level of reproductive isolation within the Non
      Valley are consistent with the different geographic characteristics and
      population sizes of the settlements. Comparison with data obtained from previous
      studies in the Eastern Italian Alps shows that the values of the investigated
      biodemographic indicators are in line with the geography and altitude of the
      area. The slight differences in temporal trend of endogamy and inbreeding can be
      correlated with different migration patterns.

PMID- 11293726
TI  - TP53 polymorphisms and haplotypes in South Amerindians and neo-Brazilians.
AB  - To evaluate the genetic diversity of Brazilian populations and contribute to the
      knowledge of their evolutionary history this study investigated three TP53
      polymorphisms (BstUI and MspI RFLPs in exon 4 and intron 6, respectively, and a
      16 bp duplication in intron 3). The populations studied were: 114 Amerindians
      from five Brazilian Indian tribes (Gaviao, Surui, Zoro, Wai-Wai and Xavante), 95
      Euro-Brazilians and 70 Afro-Brazilians. The polymorphisms were all analysed using
      PCR amplifications. Gene frequencies and haplotype prevalences were calculated
      using the ARLEQUIN software. The genetic affinities of these groups with other
      world populations were estimated by the D(A) distance and neighbour joining
      method, using the NJBAFD computer program. Neo-Brazilians (immigrants from Europe
      and Africa) generally presented more variability than Amerindians, Afro
      Brazilians being the most variable population. Among Amerindians, Gaviao is the
      only group polymorphic for the three markers. Wai-Wai showed variability in BstUI
      and MspI RFLPs, while the other tribes were monomorphic for the 16 bp A1 and MspI
      A2 alleles. A rare haplotype (1-2-1) was verified among the Wai-Wai. This
      haplotype was previously described in a Chinese sample only, but with low
      frequency. Therefore, either this combination was lost in the other tribes by
      genetic drift, recombination, or other factor, or it occurs in the Wai-Wai and
      Chinese by independent events. The Gaviao also presented a haplotype (2-1-1) not
      observed in the other Amerindians; but since it is present in Euro- and Afro
      Brazilians. its occurrence there is probably due to interethnic admixture. The
      relationships of several world populations obtained using TP53 indicates that
      this marker is very efficient in clustering populations of the same ethnic group.

PMID- 11293725
TI  - Neonatal size of low socio-economic status Black and White term births in Albany
      County, NYS.
AB  - Birth weight has long been a focus of study by epidemiologists and human
      biologists, because it reflects the quality of the intrauterine environment and
      may be used as a predictor of future growth and development. Comparisons of Black
      and White neonates in the USA have consistently shown differences in birth
      weight. Confounding variables are a major problem in any such investigation,
      especially socio-economic status which is highly correlated with race in the USA.
      This study was distinctive in the sampling of one socio-economic stratum (low
      income), and the use of five anthropometric measures in addition to birth weight.
      The goals of this study were as follows: to determine if there were differences
      in body size and body composition at birth in Black and White neonates of low
      socio-economic status (SES), and to investigate what variables might account for
      any observed variability. The sample consisted of full term Black and White
      neonates of low SES (n = 323) born in Albany, NY (1986-1997). Birth weight,
      length, head and arm circumference, and subscapular and triceps skinfolds were
      compared. Race was determined through maternal self-identification. White
      neonates were significantly larger than Black neonates in birth weight, length
      and head circumference. Among female neonates none of the anthropometric
      dimensions differed between Blacks and Whites. Among male neonates, Whites were
      significantly larger than Blacks in birth weight, length, head and arm
      circumferences. Principal components analysis reduced the six anthropometric
      dimensions to two summary measures: body size and composition. When controlling
      for social and biological variables, race and sex were significant predictors of
      body composition, but not body size. Interpretation of results and possible
      causal relationships are discussed.

PMID- 11293727
TI  - Diurnal variation in height and the reliability of height measurements using
      stretched and unstretched techniques in the evaluation of short-term growth.
AB  - Diurnal variation in stature is one potentially significant source of error in
      the evaluation of short-term growth. In order to assess the pattern of diurnal
      variation in height during a 12-h period, the standing height of two healthy
      prepubertal male siblings, 7 and 11 years of age, was measured by stretched and
      unstretched techniques five times a day at 3-h intervals over 8 consecutive days.
      The major loss of height occurred during the first 3 h after rising when the mean
      stretched height decreased by 0.94 cm (unstretched 1.03 cm). The maximal height
      loss was achieved by 1500 hours when the mean stretched height had decreased by
      1.44 cm (unstretched 1.41 cm) from that recorded in the morning. Over the next 6
      h there was a significant (p < 0.001) increment in both stretched and unstretched
      heights (+0.38 and + 0.42 cm, respectively). A stretch technique did not reduce
      the diurnal loss. In the second study daily height was measured in the same two
      siblings over 365 days: (1) to compare the reliability of measurements between
      stretched and unstretched techniques; and (2) to assess the effect of measurement
      techniques on non-linear regression analysis and time series analysis used in the
      evaluation of short-term growth. The differences between the original
      measurements and the estimates of 'true height' derived from regression curves
      were used as a measure of accuracy. A smaller SD of these differences and a
      significantly smaller number of outliers (outside +/-2 SD) than expected (p <
      0.05) was generated using the stretched technique (SD = 0.19 cm; 14 outliers)
      compared the unstretched (SD = 0.23 cm; 53 outliers). Measurement technique did
      not affect the height and height velocity regression curves and the results of
      time series analysis. In the evaluation of short-term growth we recommend that
      children should be measured by a standard stretch technique between 1800 and 2100
      hours when the diurnal variation in height is smallest.

PMID- 11293722
TI  - The genetics of phenylthiocarbamide perception.
AB  - The ability to taste the bitter compound phenylthiocarbamide (PTC) and related
      chemicals is bimodal, and all human populations tested to date contain some
      people who can and some people who cannot taste PTC. Why this trait has been
      maintained in the population is uncertain but this polymorphism may influence
      food selection, nutritional status or thyroid metabolism. The gene product that
      gives rise to this phenotype is unknown, and its characterization would provide
      insight into the mechanism of bitter taste perception. Although this trait is
      often considered a simple Mendelian trait, i.e. one gene two alleles, a recent
      linkage study found a major locus on chromosome 5p15 and evidence for an
      additional locus on chromosome 7. The development of methods to identify these
      genes will provide a good stepping-stone between single-gene disorders and
      polygenic traits.

PMID- 11293728
TI  - Comparison of soft tissue body composition in postmenopausal women with or
      without hormone replacement therapy considering the influence of reproductive
      history and lifestyle.
AB  - OBJECTIVES: To examine long-term effects of at least 5 years' conventional
      hormone replacement therapy (HRT), reproductive history and lifestyle on fat mass
      and muscle mass in postmenopausal women. RESEARCH DESIGN AND METHODS: A cross
      sectional retrospective approach was used, including 64 healthy women (56-69
      years, mean age 63.4 years). Hormone users were compared with age-matched non
      users with respect to (a) type of HRT used (oestrogen vs oestrogen plus gestagen
      vs no hormones), (b) categories of oestrogens used (oestradiol-based oestrogens
      vs conjugated equine oestrogens vs no oestrogens) and (c) categories of gestagens
      used (testosterone derivatives vs progesterone derivatives vs no gestagens). Data
      on hormone use, reproductive history (age at menarche, age at menopause, number
      of years postmenopausal, number of children) and lifestyle (physical activity
      level, alcohol consumption, smoking habits) were collected by questionnaires.
      Body composition was analysed by multiple-frequency bioelectrical impedance
      analysis, estimating fat mass, fat-free mass and body cell mass as absolute
      values (FM, FFM, BCM, respectively) and percentages of body weight (%FM, %FFM,
      %BCM). RESULTS: Analysis of covariance, adjusting body composition variables for
      body mass index, showed that (a) unopposed oestrogen users, oestrogen plus
      gestagen users and non-users did not differ significantly in body composition
      variables, (b) users of oestradiol-based oestrogens had significantly more BCM
      than oestrogen abstainers (p < 0.05), (c) users of testosterone-based gestagens
      had more BCM than gestagen abstainers (p = 0.05). Stepwise multiple regression
      analyses, including HRT-related, reproductive and lifestyle variables, indicated
      that the duration of HRT (p < 0.05) and physical activity level (p = 0.01) were
      significant positive predictors of %BCM, whereas the number of children
      significantly positively predicted FM and %FM (each p < 0.05). No significant
      associations between fat-free mass and HRT were found. CONCLUSIONS: The results
      suggest that conventional doses of oestrogens and gestagens used in HRT might be
      a factor in preserving muscle mass after long-term administration. It is
      recommended that BCM is used instead of FFM as an indicator of muscle mass.
      Studies relating muscle mass to HRT in postmenopausal women should consider
      physical activity as a possible confounding variable.

PMID- 11293729
TI  - Familial correlation and segregation analysis of forced expiratory volume in one
      second (FEV1), with and without smoking adjustments, in a Tucson population.
AB  - BACKGROUND: Previous researchers have found significant familial aggregation but
      no evidence of Mendelian inheritance of forced expiratory volume in one second
      (FEV1) in general population studies. However, the influence of cigarette smoking
      on familial aggregation of FEV1 has been difficult to assess in these studies.
      OBJECTIVES: The main objective of our study was to attempt to discern the effects
      of smoking on familial correlation and segregation models of FEV1. SUBJECTS AND
      METHODS: In a randomly selected sample of white, non-Mexican American families in
      Tucson, Arizona, we performed two separate familial correlation and segregation
      analyses of FEV1, one adjusted for cigarette smoking and one unadjusted for
      smoking. In both, initial survey measures of FEV1 for 1329 females and 1291 males
      in 746 families were standardized for gender, age, height and height-squared
      using piecewise linear regression models. In the smoking-adjusted model, total
      number of pack-years smoked, current and ex-smoking status, and the interaction
      between total pack-years and current smoking status were also included. RESULTS:
      FEV1 was significantly correlated among sibling pairs and parent-offspring pairs
      (both p < 0.001), regardless of smoking adjustment, but sibling correlation was
      significantly higher than parent-offspring correlation (p < 0.05), suggesting
      additional effects beyond common parentage. Spousal correlations were not
      significant even when both spouses smoked. We found no evidence of major gene
      segregation of FEV1, with or without smoking adjustment, and all of the
      segregation models were significantly different from the unrestricted model.
      CONCLUSIONS: The best-fitting model was an environmental model with three
      distinct distributions of FEV1 and significant residual familial effects. A
      significant familial component suggests the presence of polygenic factors and/or
      effects due to a shared environment (multifactorial). That familial correlations
      of smoking-adjusted and smoking-unadjusted residuals were not appreciably
      different suggests that current smoking status and number of pack-years smoked do
      not account for the observed familial aggregation of FEV1.

PMID- 11293730
TI  - Psychosocial dimensions of paediatric cardiology--more than statistics and
      testing?

PMID- 11293731
TI  - Inhaled nitric oxide and congenital cardiac disease.

PMID- 11293732
TI  - Cognitive, and behavioural and emotional functioning of young children awaiting
      elective cardiac surgery or catheter intervention.
AB  - AIMS: To assess the cognitive, and behavioural and emotional functioning of
      children aged 3 months to 7 years shortly before elective cardiac surgery or
      elective interventional catheterisation. METHODS: We used the Bayley Scales of
      Infant Development, and the McCarthy Scales of Children's Abilities, to measure
      cognitive functioning. The Child Behavior Checklist was used to assess
      behavioural and emotional problems. RESULTS: We found no significant differences
      in mean cognitive scores for children scheduled for cardiac surgery or
      interventional catheterisation when compared with reference groups. This was also
      the case for children awaiting cardiac surgery as opposed to those awaiting
      interventional catheterisation, and for those below as compared to those above
      the age of 2.5 years. Overall, our results regarding behavioural and emotional
      functioning were comparable to those of normative reference groups. The only
      difference found was that the children scheduled for cardiac surgery and aged
      from 2 to 3 years had significantly higher scores on the Child Behavior Checklist
      than did peers from normative groups. CONCLUSION: Cognitive, and behavioural and
      emotional functioning, both for young children awaiting elective cardiac surgery
      and interventional catheterisation, can be considered as quite favourable.

PMID- 11293733
TI  - Pathogenetic mechanisms of venous congestion after the Fontan procedure.
AB  - BACKGROUND: The hemodynamic status after a Fontan type procedure for definitive
      palliation of functionally univentricular hearts is dominated by a high central
      venous pressure, which seems to be one of several factors responsible for venous
      congestion appearing as a frequent complication in the early and late
      postoperative course. The purpose of our study was to find other hemodynamic
      parameters correlating with the presence of venous congestion and effusions in
      these patients. METHODS: We compared the hemodynamic data of 18 patients who had
      an uneventful long-term course after a Fontan type procedure with the respective
      data of 10 patients who developed symptoms of venous congestion in the immediate
      postoperative period. Based on a theoretical model, we developed an algorithm to
      calculate mean hydrostatic capillary pressure from mean arterial pressure,
      systemic vascular resistance index and central venous pressure. RESULTS:
      Pulmonary vascular resistance index (2.1 +/- 1.0 mmHg L-1 min m2), mean left
      atrial pressure (9.7+/-4.0 mmHg) and cardiac index (3.6+/-0.6 l/min/m2) are
      mainly normal in patients with venous congestion in the immediate postoperative
      period, but mean hydrostatic capillary pressure is significantly higher compared
      to patients without venous congestion (24.3+/-3.1 vs 18.3+/-4.0 mmHg). Lower mean
      hydrostatic capillary pressures in these patients are due to a highly significant
      increase of systemic vascular resistance index (18.6+/-4.2 versus 33.6+/-6.6 mmHg
      L-1 min m2) and a concomitant decrease of cardiac index to 2.4+/-0.3 l/min/m2.
      CONCLUSIONS: The increase of mean hydrostatic capillary pressure, caused by high
      central venous pressures but also by relatively low systemic vascular resistance
      indexes, seems to be the hemodynamic key parameter responsible for venous
      congestion and effusions in patients after a Fontan type procedure in the
      immediate postoperative period.

PMID- 11293734
TI  - Dilation of the ascending aorta in childhood: 4 cases without obvious
      predisposing disease.
AB  - Dilation of the ascending aorta is rare in childhood. When seen, it is usually
      associated with some form of connective tissue disease or predisposing cardiac
      malformations, especially an aortic valve with two leaflets. We describe four
      children in whom significant dilation of the ascending aorta was encountered as
      an incidental finding. No patient had any sign of an associated connective tissue
      disease, nor did we detect any predisposing cardiac anomalies. One patient had
      undergone surgical ligation of the arterial duct in infancy, whilst another had
      undergone repair of aortic coarctation, also in infancy. A third child has had
      repair of an atrioventricular septal defect with exclusively atrial shunting,
      whereas the fourth patient had a structurally normal heart. The aortic valve had
      three leaflets, and was functionally normal in all. The dilation of the ascending
      aorta was progressive in all patients, and finally surgical treatment was
      recommended, relying on the guidelines established for the management of patients
      affected with the Marfan syndrome.

PMID- 11293735
TI  - The effect of implantation of aortic stents on compliance and blood flow. An
      experimental study in pigs.
AB  - Balloon dilation of coarctation of the aorta has been found to be an effective
      modality for treatment. Recently, in the older child and adult, implantation of
      endovascular stents has been considered a clinical alternative to dilation alone.
      Little is known, however, of the effect of implantation of stents on aortic
      compliance. To investigate this impact of implantation, we studied 18 piglets,
      divided into experimental and control groups. At median weight of 14 kg, 2 pairs
      of ultrasonic crystals were implanted on the aortic wall. After 1 week, all
      animals underwent catheterization. In the experimental group, a 3 cm long balloon
      expandable stent was implanted in the descending thoracic aorta between the pairs
      of crystals. Measurements of arterial pressure and dimensions were performed
      before implantation and immediately thereafter, and at follow-up catheterization.
      The index of stiffness, beta, and the the elastic modulus of aortic pressure
      strain, were calculated as indexes of arterial compliance. The change in
      compliance during the period of study was not different between groups. At follow
      up, no difference was observed between groups in the velocity of the aortic pulse
      wave, the augmentation index, or the maximum velocity of flow of blood. The
      stents remained patent and did not affect aortic growth or medial wall thickness.
      There was no difference between groups in levels of plasma renin activity and
      serum aldosterone. In this animal model studied over the short term, therefore,
      implantation of stents does not affect aortic compliance. Further studies are
      required to elucidate the long term effects of stents on the hemodynamics
      affecting the aortic wall and local flow dynamics.

PMID- 11293736
TI  - Abbreviated combined anatomical/electrophysiological approach for catheter
      ablation of atrioventricular nodal reentrant tachycardia in children.
AB  - Atrioventricular nodal reentrant tachycardia was proven during electrophysiologic
      study in 41 children, aged from 3.7 to 16 years, who were referred for catheter
      ablation of symptomatic supraventricular tachycardia. Using an abbreviated
      combined anatomical and electrogram-guided approach for selective ablation of the
      slow pathway, a steerable ablation catheter was placed at the inferior region of
      the vestibule of the tricuspid valve close to the orifice of the coronary sinus,
      with the intention of recording a multicomponent local atrial electrogramm during
      sinus rhythm. If application of radiofrequency current of 500 kHz at 70 degrees C
      at this site did not result in a slowly accelerated junctional rhythm, at a rate
      of less than 120 beats per minute, the catheter was stepwise advanced up to a
      position midway towards the apex of the triangle of Koch for additional
      applications of energy. Ablation was achieved in 35 of the patients. In 6
      patients, the slow pathway was modulated such that the tachycardia could no
      longer be induced. The number of applications of energy ranged from 1 to 19, with
      a median of 6 applications. The mean period of fluoroscopy was reduced to 15.6
      (4.3 to 39.8) minutes, while the overall duration of the catheterization
      procedures ranged from 88 to 280 (mean 173.2) minutes. In none of the patients
      did we observe permanent high grade atrioventricular block. During follow-up over
      a mean of 4.1 years, two patients had recurrence of tachycardia, corresponding to
      a 95% rate of success in the midterm. We conclude that selective radiofrequency
      ablation of the slow pathway using the abbreviated anatomical and
      electrophysiological approach is a safe and curative therapeutic approach in
      children with atrioventricular nodal reentrant tachycardia. Periods required for
      fluoroscopy can be significantly reduced, and mid-term results are excellent.

PMID- 11293737
TI  - The repeatability of echocardiographic determination of right ventricular output
      in the newborn.
AB  - BACKGROUND: Non-invasive measurement of left ventricular output has been shown to
      be a repeatable technique. Little is known about the repeatability using
      echocardiography in determining pulmonary arterial diameters or right ventricular
      output. AIMS: To find the most repeatable point at which to measure pulmonary
      arterial diameter, and to compare the repeatability of determining right
      ventricular output with left ventricular output. METHODS: We assessed the Intra
      observer and inter-observer repeatability for measuring the diameter of the
      pulmonary trunk in 24 term and 26 preterm infants, respectively. Interobserver
      repeatability was assessed for the diameters of the pulmonary trunk and aorta,
      for stroke distance, and for left and right ventricular output. RESULTS: The
      coefficients of variation for intra-observer repeatability were 4%, 7.5% and 9%
      respectively for measurements of the pulmonary valve, the pulmonary trunk, and
      the right ventricular outflow tract. There were significant differences between
      observers for measurement of the pulmonary trunk (p<0.001) and right ventricular
      outflow tract (p=0.011) but not for the pulmonary valve measured in either its
      long (p=0.22) or short axis (p=0.22). Significant differences between observers
      were also found for the pulmonary stroke distance measured in the long axis
      (p=0.004) and aortic diameter at end-diastole (p<0.001). The other parameters did
      not differ significantly and were used to calculate right and left ventricular
      output, respectively. Mean left ventricular output was 241 mls/kg/min, with mean
      differences between observers of 0.6 mls/kg/min (95% confidence interval (CI): 
      39.2 to 40.3 mls/kg/min). Mean right ventricular output was 255 mls/kg/min, with
      mean differences of 0.3 mls/kg/min (95% CI: -24.1 to 23.4 mls/kg/min).
      CONCLUSION: Measuring the diameter of the pulmonary trunk at the base of the
      valvar hinge points was most repeatable. Repeatability of right ventricular
      output was similar to that of left, with absolute values similar to those
      published by other workers.

PMID- 11293738
TI  - Perioperative administration of angiotensin converting enzyme inhibitors
      decreases the severity and duration of pleural effusions following bidirectional
      cavopulmonary anastomosis.
AB  - BACKGROUND: Pleural effusions after bidirectional cavopulmonary anastomosis
      remain a significant cause of morbidity. Prolonged effusions in such patients
      have been associated with persistent elevations in plasma renin and angiotensin
      II. METHODS: We conducted a controlled study in 36 patients (median age 8 months)
      undergoing bidirectional cavopulmonary anastomosis. Enalapril (5 mcg/kg) was
      administered intravenously within 1 hour of surgery and every 12 hours thereafter
      in 18 patients; when these patients were tolerating feeds, enalapril was switched
      to enteral captopril (3 mg/kg/day) every 8 hours. The other 18 patients did not
      receive perioperative angiotensin converting enzyme inhibitors. Using
      standardized criteria for discontinuation of chest tubes (< 2 mL/kg/day), volume
      and duration of pleural drainage were compared between groups. RESULTS. There
      were no differences between groups in demographic, diagnostic, or hemodynamic
      factors. There was no difference in cardiopulmonary bypass time between groups
      and no difference in postoperative pulmonary arterial pressures. The duration of
      pleural drainage was shorter (2.2+/-1.4 vs 5.9+/-1.4 days, p<0.001) and the
      volume less during the first 24 hours (4.7+/-1.2 vs 7.7+/-2.1 mL/kg, p<0.001) and
      overall (10.6+/-2.4 vs 19.6+/-4.5 mL/kg, p<0.001) in patients who received
      angiotensin converting enzyme inhibitors than those who did not. Readmission for
      persistent effusions was required in 3 patients who did not receive angiotensin
      converting enzyme inhibitors and none who did (p=0.11). CONCLUSIONS:
      Perioperative administration of angiotensin converting enzyme inhibitors is
      associated with decreased severity and duration of pleural effusions following
      bidirectional cavopulmonary anastomosis.

PMID- 11293739
TI  - The value of transesophageal echocardiography in transcatheter closure of atrial
      septal defects in the oval fossa using the Amplatzer septal occluder.
AB  - BACKGROUND: From January, 1997, as part of an international multicentric trial,
      we have been closing small-to-moderate atrial septal defects within the oval
      fossa using the Amplatzer Septal Occluder (ASO, AGA Medical). METHODS: All
      patients with defects within the oval fossa deemed potentially suitable for
      transcatheter closure were investigated by transesophageal echocardiography with
      the aim of gaining extra information that might alter the decision to use the
      device to close the defect. Views were obtained in transverse and longitudinal
      planes, permitting measurements of the diameter of the defect, and its distance
      from the atrioventricular valves, coronary sinus, and pulmonary veins.
      Additionally, we sought to identify multiple defects, and to exclude sinus
      venosus defects. RESULTS: Of 56 patients with left-to-right shunts, 41 (73.2%)
      were deemed suitable for closure with the Amplatzer Septal Occluder. All
      underwent the procedure successfully, with no complications. This includes 5
      patients with multiple small defects that were sufficiently close to the main
      defect to be closed with a single device. Only two of these had been detected on
      the transthoracic study. In the remaining 15 of 56 patients, transcatheter
      closure was deemed unsuitable. In 9 patients, this was due to the limitation of
      the size of the device available during the period of study, this representing a
      relative contraindication. In the remaining 6 (10.7%), transcatheter closure was
      not performed because multiple defects were too far apart to be closed with a
      single device in 3 patients, two patients were noted to have a sinus venosus
      defect, and another was noted to have anomalous connection of the right upper
      pulmonary vein to the right atrium. Excluding patients contraindicated due to the
      size of the defect alone, transesophageal echocardiography provided extra
      information in one-tenth of our patients, which altered the decision regarding
      management. CONCLUSION: Transesophageal echocardiography is indispensable in the
      evaluation of patients undergoing transcatheter closure of atrial septal defect.

PMID- 11293740
TI  - Endomyocardial fibrosis in children.
AB  - We describe 10 children with endomyocardial fibrosis who underwent surgical
      treatment between 1978 and 1999. Seven were male and 3 female, with an age range
      from 4 to 15 years, having a mean age of 11 years. All were in the final stage of
      heart failure. Three had biventricular disease, 6 had involvement of the right
      ventricle alone, and one had endomyocardial fibrosis confined to the left
      ventricle. There were 3 deaths (30%) in the postoperative period due to low
      cardiac output. The 7 survivors were followed up for a period ranging from 12 to
      168 months, with a mean of 72 months. Two late deaths have occurred resulting
      from heart failure and infectious endocarditis. Five (50%) children are still
      alive. Two required 3 reoperations for dysfunction of the inserted valvar
      prosthesis. One patient is in functional Class IV, and 4 are in Class II to III,
      despite intensive medical treatment. It is concluded that surgery for
      endomyocardial fibrosis is an essentially palliative procedure and, especially in
      children, the results of surgical treatment leave much to be desired.

PMID- 11293741
TI  - Constrictive chronic pericarditis in children.
AB  - Constrictive pericarditis is a uncommom disease in children. We have now
      encountered pericardial thickening as the cause of severe constrictive physiology
      in two patients, one also having haemodynamic features of restrictive
      cardiomyopathy. Both patients, who had refractory ascites and evidence of
      increased systemic venous pressure, underwent Doppler echocardiography, cardiac
      catheterisation, and magnetic resonance imaging. Resonance imaging failed to show
      any thickning of the pericardium, but cardiac catheterisation revealed diastolic
      equalisation of pressures in all four chambers, with only mild elevation of
      pulmonary pressure in the first patient, but nearly equalisation of diastolic
      pressure, and a very high pulmonary arterial pressure with a difference of 7 mm
      Hg between the end diastolic pressures in the two ventricles in the second
      patient. Doppler revealed a restrictive pattern of mitral inflow, with high E and
      small A velocities and a short deceleration time. The clinical background did not
      suggest pericardial disease in either of the patients. We conclude that a careful
      search is needed to uncover constrictive pericarditis when there is no previous
      disease which may suggest late pericardial constriction. The haemodynamic
      features of restrictive cardiomyopathy can co-exist with pericardial restriction,
      and differentiation between the two entities is critical in view of the diverse
      management and prognosis of the two conditions.

PMID- 11293742
TI  - Transcatheter closure of various types of defects within the oval fossa using the
      double umbrella device (CardioSEAL)--feasibility and echocardiographic follow-up.
AB  - Data on long-term follow-up for closure of so-called secundum type" atrial septal
      defects within the oval fossa using recently developed devices are limited, and
      results focused on presence of residual shunting. The purpose of our study was to
      report the experience from a single center establishing the effectiveness of
      transcatheter closure in patients with various types of defect other than those
      located centrally within the oval fossa. A total of 72 patients was included in
      this study. On transesophageal echocardiography, the size of the defects varied
      from 6 to 18 mm, with estimation of the stretched diameter from 11 to 21 mm. The
      ratio of stretched diameter to the extent of the residual septum ranged from 0.28
      to 0.54. Mean follow-up was 30.5+7.4 months, with a range from 13 to 42 months.
      The rate of closure using devices with diameters from 28 to 40 mm increased from
      80% immediately after implantation to 93% in the 57 patients examined 24 months
      after implantation. For further analysis, we compared the 44 patients with a
      solitary, centrally located, defect to 28 having morphological variations,
      including superiorly located defects with deficient superior and aortic rims,
      multifenestrated and aneurysmal defects, or isolated additional defects. There
      was no incidence of formation of thrombus, sustained atrial arrhythmia, or
      infective endocarditis. Residual shunting was not influenced by location or
      morphology of the defects, but increased with size, stretched diameter, and the
      ratio of pulmonary to systemic flows. Serial transthoracic echocardiographic
      findings revealed malposition of one right-sided superior arm of the device in 8
      patients, while protrusion of one left-sided arm onto the right atrial aspect was
      observed in 3 patients. Fluoroscopy showed fatigue fracture of a single arm in 7
      patients (9.7%) within the first 6 months after implantation. These results
      demonstrate that transcatheter closure with the non self-centering double
      umbrella device was effective and safe on medium-term follow-up, and could be
      extended to defects within the oval fossa having various morphologies. Residual
      shunting resolved with time, and was not related to either morphology or the
      position of the device.

PMID- 11293743
TI  - Images in congenital heart disease. Postoperative "white-out" from superior caval
      venous obstruction.

PMID- 11293744
TI  - High-altitude precipitation and exacerbation of protein-losing enteropathy after
      a Fontan operation.
AB  - We describe the development and exacerbation of protein-losing enteropathy after
      relocating to an environment at an altitude of 3695 feet in El Paso, Texas, in a
      patient who had undergone a Fontan operation. This report should heighten
      awareness to the possibility of such patients developing protein-losing
      enteropathy at high-altitude, with hypoxemia-induced pulmonary vasoconstriction,
      and subsequent elevation of central venous pressure, the most likely underlying
      mechanism.

PMID- 11293745
TI  - Ectopic atrial tachycardia due to aneurysm of the right atrial appendage.
AB  - We report an infant with ectopic atrial tachycardia, due to an aneurysm of the
      right atrial appendage, who developed congestive heart failure. Although catheter
      ablation was transiently successful, tachycardia recurred 2 days later. The
      aneurysm of the right atrial appendage was resected successfully by surgery, and
      thereafter she did well, reverting to normal sinus rhythm.

PMID- 11293746
TI  - Late cardiac tamponade after transcatheter closure of atrial septal defect with
      Cardioseal device.
AB  - Cardiac tamponade occurring late after interventional closure of defects within
      the oval fossa is a very rare but life-threatening complication. We describe such
      an occurrence after use of a Cardioseal device to close an interatrial
      communication. Two arms of the device had perforated left atrial wall. The device
      was removed at surgery, and the defect closed uneventfully. All available means
      should be used to identify this complication.

PMID- 11293747
TI  - Rapid onset of intrapulmonary arteriovenous shunting after surgical repair of
      tetralogy of Fallot with pulmonary atresia.
AB  - We describe a 2-year-old girl with tetralogy of Fallot and pulmonary atresia,
      palliated as a neonate with a right modified Blalock Taussig shunt, who developed
      severe cyanosis following total correction in the absence of corresponding
      evidence of parenchymal lung disease on the chest X-ray. Selective pulmonary
      angiography showed new intrapulmonary shunting involving only the right middle
      and lower lobes only. The cyanosis resolved rapidly subsequent to inhalation of
      nitric oxide. To our knowledge, this is the first documented case of rapid onset
      of localised intrapulmonary right-to-left shunting, involving only two lung
      lobes, following biventricular repair for complex congenital heart disease.

PMID- 11293748
TI  - Noncompaction of the myocardium associated with Roifman syndrome.
AB  - Noncompaction of the ventricular myocardium, sometimes referred to as "spongy
      myocardium", appears as excessive and prominent trabeculations and deep
      intratrabecular recesses within the ventricular wall, usually involving the left
      ventricle, although the right ventricle and interventricular septum can also be
      affected. It may occur with or without additional heart malformations. Roifman
      syndrome is a constellation of antibody deficiency, spondyloepiphyseal dysplasia,
      facial dysmorphism, growth retardation, and retinal dystrophy. We report a
      patient with Roifman syndrome who presented with noncompaction of the left
      ventricular myocardium. Our findings expand the spectrum of diseases associated
      with noncompaction. The recognition of noncompaction among patients with Roifman
      syndrome is important, as the immune deficiencies may be subtle and undiagnosed
      until adulthood. Thus, some patients may first present with cardiac failure.

PMID- 11293749
TI  - Takayasu disease masquarading as interruption of the aortic arch in a 2-year-old
      child.
AB  - Takayasu disease is a chronic, progressive inflammatory vasculitis of large and
      medium-sized vessels, which commonly presents in adulthood. This case report
      describes a 2 year old girl who presented with acute heart failure and complete
      occlusion of the aortic arch and was subsequently diagnosed with Takayasu
      disease. As far as we can determine, this is the first report of such an acute
      and atypical presentation of Takayasu disease at such a young age.

PMID- 11293750
TI  - A new system for rapid large-caliber percutaneous transhepatic drainage in
      patients with obstructive jaundice: a prospective randomized trial.
AB  - BACKGROUND AND STUDY, AIMS: Percutaneous access to the biliary tract is an
      important diagnostic and therapeutic tool in the management of biliary diseases.
      It is usually chosen when the endoscopic approach via endoscopic retrograde
      cholangiopancreatography (ERCP) fails, or is not possible. Once established, the
      percutaneous tract is then used for the treatment of biliary stones and
      strictures. To establish a percutaneous tract with a caliber large enough for
      cholangioscopy to be performed, or for a large-bore permanent drainage tube to be
      inserted, stepwise dilation up to 14 Fr or 16 Fr is usually required. We present
      here a new method of rapid dilation using specially designed materials, including
      a stiffenable guide wire and specially adapted bougies. PATIENTS AND METHODS:
      Consecutive patients undergoing percutaneous drainage for biliary diseases were
      included in this prospective study, over a 19-month period. After establishment
      of a 10-Fr transpapillary drain, the patients were randomly assigned to either
      conventional percutaneous transhepatic biliary drainage (PTBD) or stepwise
      dilation using the new method, aiming at a need for only one further session,
      using a specially designed stiffenable metal guide wire of 6.6 Fr and plastic
      bougies. The details of the procedure (duration, materials used, technical ease),
      initial and later complications, assessment by the patients, and procedural costs
      were compared between the two groups. RESULTS: Of the 60 patients included, 29
      were randomly assigned to group I (the new method) and 31 to group II (the
      conventional approach); there were no significant differences between the two
      groups in terms of clinical data or biliary pathology. The clinical efficacy of
      PTBD was similar in the two groups, although three patients in group II were
      switched to the new procedure because of failure of dilation using the
      conventional approach. The rates of major complications (four of 29 in group I,
      five of 31 in group II) and patient tolerance were also similar. However, the new
      procedure led to a significant reduction in the cumulative procedure duration
      (20.1 minutes vs 30.1 minutes), mean number of sessions (1.1 vs. 1.7), and mean
      number of hospital days (2.0 vs 5.5), and was therefore also cost-effective,
      reducing costs from a mean of 5813 to 2581 German marks (DM) per patient.
      CONCLUSIONS: The new system for rapid establishment of large-caliber PTBD offers
      significant advantages in terms of saving hospital resources while maintaining
      clinical efficacy.

PMID- 11293751
TI  - Endoscopic induction of mucosal fibrosis by argon plasma coagulation (APC) for
      esophageal varices: A prospective randomized trial of ligation plus APC vs.
      ligation alone.
AB  - BACKGROUND AND STUDY AIMS: Esophageal varices are treated by endoscopic ligation
      with or without sclerotherapy. Here we used argon plasma coagulation (APC) to
      promote mucosal fibrosis and compared the efficacy of ligation plus APC with
      ligation alone in the treatment of esophageal varices. PATIENTS AND METHODS: Our
      prospective study included 30 patients with esophageal varices randomly assigned
      to receive APC after ligation (combined group) and 30 patients assigned to
      receive ligation only (ligation group). Endoscopic ligation was performed until
      the varix shrank to F1 without red color sign or smaller. This was followed by
      induction of fibrosis of the distal esophageal mucosa using APC in the combined
      group. APC was performed using an argon gas at a flow rate of 1.5-2 l/min and a
      high frequency arc output of 50-60 W. Treatment outcome and complications were
      compared between the two groups. RESULTS: The mean follow-up time was 18.5+/-6.8
      and 15.8+/-7.7 months (+/- SD) for the combined and ligation groups,
      respectively. The number of treatment sessions was slightly lower in the ligation
      group (2.9+/-0.6 vs. 2.5+/-0.6, P<0.05). The number of ligation bands used was
      not different between the two groups (13.4+/-3.1 vs. 14.9+/-2.4). The cumulative
      recurrence-free rate at 24 months after treatment in the combined group was
      significantly higher than in the ligation group (74.2% vs. 49.6%, P < 0.05). A
      significantly higher incidence of pyrexia was encountered in the combined group
      (P <0.05), but the incidences of other complications were similar in both groups.
      CONCLUSION: Our results indicate that endoscopic ligation of esophageal varices
      combined with APC is superior to ligation alone. Since APC is theoretically well
      suited for mucosal fibrosis therapy, it can be used for the complete elimination
      of esophageal varices and for fibrosis of the distal esophageal mucosa.

PMID- 11293752
TI  - Follow-up of selective endoscopic ultrasonography and/or endoscopic retrograde
      cholangiography prior to laparoscopic cholecystectomy: a prospective study of 300
      patients.
AB  - BACKGROUND AND STUDY AIMS: This prospective study evaluated the selective use of
      endoscopic retrograde cholangiography (ERC) and endoscopic ultrasonography (EUS)
      in the context of laparoscopic cholecystectomy (LC). PATIENTS AND METHODS:
      Between 1993 and 1998, LC for symptomatic gallstones was indicated in 300
      consecutive patients. In order to diagnose and treat choledocholithiasis
      preoperatively, we performed, on the basis of preoperative criteria, ERC in "high
      risk" patients and EUS in "intermediate-risk" patients. Choledocholithiasis was
      treated by preoperative biliary endoscopic sphincterotomy (BES). LC was performed
      either after the endoscopic procedure or directly in "low-risk" patients.
      RESULTS: A total of 104 patients (35%) had 118 preoperative procedures: a) EUS (n
      = 68; feasibility 100%): choledocholithiasis was observed in 14/68 patients
      (21%); b) ERC (n = 50; feasibility 94%): 36 ERC were indicated on on preoperative
      criteria, and 14 on the basis of EUS results. Choledocholithiasis was found in
      41/ 50 patients (82%) (13/14 patients with positive EUS), 19% of "intermediate
      risk" patients, and 78% of "high-risk" patients; ERC failed in three patients who
      had no choledocholithiasis on subsequent intraoperative cholangiography (IOC).
      Clearance of the common bile duct (CBD) was achieved after BES in 41/41 patients.
      There was no mortality; complications occurred in 4/ 300 patients (1%). No
      retained stones were found in patients of any of the three groups, after a mean
      follow-up of 32 months. CONCLUSIONS: Combined endoscopic and laparoscopie
      management of cholecystolithiasis and choledocholithiasis is a viable option and
      is optimized by the use of EUS.

PMID- 11293753
TI  - New endoscopic treatment for intramucosal gastric tumors using an insulated-tip
      diathermic knife.
AB  - BACKGROUND AND STUDY AIMS: For one-piece resection the conventional technique of
      endoscopic mucosal resection (EMR) is limited to gastric mucosal tumors of 10 mm
      or less in size. In this retrospective study, we investigated the efficacy and
      complications associated with a new EMR method, using an insulated-tip diathermic
      knife (IT-EMR). PATIENTS AND METHODS: In a total of 41 patients gastric mucosal
      tumors were resected using IT-EMR. RESULTS: One-piece resection rates were 82%
      (14/17) for lesions of 10 mm or less, 75% (12/16) for those between 11 and 20 mm,
      and 14% (1/7) for those of over 20 mm. Complication rates for severe bleeding and
      perforation were 22% and 5%, respectively. With a median follow-up period of 32
      months, no recurrence was observed after these procedures. CONCLUSIONS: Compared
      with conventional EMR, this new method may have significant benefits,
      particularly regarding one-piece resection of lesions between 11 and 20 mm in
      size, and may also have a lower recurrence rate.

PMID- 11293754
TI  - Use of an overtube for enteroscopy--does it increase depth of insertion? A
      prospective study of enteroscopy with and without an overtube.
AB  - BACKGROUND AND STUDY AIMS: Although a stiffening overtube is commonly used with
      push enteroscopy, in the belief that this will allow increased insertion into the
      small intestine, there is no prospective data to support this view. The aim of
      this study is to prospectively study the depth of insertion into the small
      intestine at enteroscopy with and without an overtube. PATIENTS AND METHODS: A
      total of 38 patients referred for enteroscopy were prospectively studied.
      Alternate enteroscopies were performed with or without an overtube; therefore 19
      patients had enteroscopy with and 19 without an overtube. The groups were well
      matched for age, sex, indication, use of fluoroscopy, and dedicated anesthetic
      assistance. Depth of insertion was assessed by advancing the enteroscope as far
      as possible, then straightening the enteroscope until the tip began withdrawing.
      The difference between the straightened insertion depth and the distance from the
      incisors to the pylorus was recorded as the insertion depth beyond the pylorus.
      This was considered the major end point. Statistical analysis was performed using
      the Mann-Whitney test for nonparametric data. RESULTS: The median straightened
      total insertion depth from the incisors was greater when enteroscopy was
      performed with an overtube compared with enteroscopy without an overtube (125 cm
      vs. 110 cm, P=0.05). The median straightened insertion depth beyond the pylorus
      was significantly greater with overtube use (70 cm vs. 50 cm, P = 0.01). No
      significant difference between the groups was observed in terms of the likelihood
      of significant findings at enteroscopy. CONCLUSIONS: Use of an overtube for push
      enteroscopy results in significantly deeper insertion into the small intestine.
      Although a larger study would be needed to demonstrate an increase in diagnostic
      yield and to confirm the safety of overtube use, this study does provide the
      first objective evidence of an advantage in terms of insertion depth.

PMID- 11293755
TI  - Anal carcinoma: prognostic value of endorectal ultrasound (ERUS). Results of a
      prospective multicenter study.
AB  - BACKGROUND AND STUDY AIMS: The classification of anal carcinoma is based on the
      clinical examination and the estimation of the tumor height (Union Internationale
      Contre le Cancer (UICC) 1987 Classification). This classification has a direct
      therapeutic application since tumors which are designated T1 and T2 are generally
      treated by radiotherapy whereas T3, T4 or N+ lesions are treated by concomitant
      radiation and chemotherapy. The aim of this prospective multicenter study was to
      evaluate endorectal ultrasound (ERUS) and to define an ERUS-based classification.
      PATIENTS AND METHODS: Between January 1994 and May 1997, 146 patients (42 men and
      104 women; mean age, 63) from eight different centers were studied prospectively.
      The ERUS classification incorporates disease of the anal canal and the perirectal
      lymph nodes, thus: usT1 describes involvement of the mucosa and submucosa with
      sparing of the internal sphincter; usT2, involvement of the internal sphincter
      with sparing of the external sphincter; usT3, involvement of the external
      sphincter; usT4, involvement of a pelvic organ; N0 describes no suspicious
      perirectal lymph nodes, and N+, perirectal lymph nodes fulfilling endosonographic
      criteria for malignancy (e.g. round, hypoechoic). Tumors classified as UICC T1-T2
      (<4cm) N0 were treated by radiotherapy alone, whereas lesions with a UICC
      classification of T2 (> 4 cm), T3-T4, N0-N1-2-3 received combined
      radiochemotherapy. RESULTS: Data concerning the treatment and follow-up were
      available for 115/146 patients (78.7%). We compared the prognostic importance of
      the two classification schemes for treatment response and the rate of local
      relapse (chi-squared test). A significantly greater proportion of T1-T2N0 lesions
      classified by ERUS had a complete response to treatment than those classified by
      conventional UICC staging (94.5% vs. 80%, respectively; P = 0.008). The ERUS T
      and N stage were significant predictors of relapse (P=0.001 and P=0.03,
      respectively) whereas the corresponding clinical (UICC) stages were not (P = 0.4
      and P = 0.5, respectively). Using a Cox model, usT stage was the only significant
      predictive factor for patient survival. CONCLUSION: This muticenter prospective
      study demonstrated the superiority of ERUS-based staging over traditional
      clinical staging in the prediction of important outcomes such as local tumor
      recurrence and patient survival.

PMID- 11293756
TI  - Preoperative evaluation of submucosal invasive colorectal cancer using a 15-MHz
      ultrasound miniprobe.
AB  - BACKGROUND AND STUDY AIMS: Recently, it was reported that focal submucosal
      invasive colorectal cancer could be treated by polypectomy or endoscopic mucosal
      resection (EMR) because of the rarity of lymph-node metastasis. Our objective was
      to examine the accuracy and efficacy of a 15-MHz ultrasound miniprobe in the
      preoperative evaluation of the degree of submucosal invasion in colorectal
      cancer. PATIENTS AND METHODS: A total of 35 patients with submucosal invasive
      colorectal cancer who underwent ultrasonography with a miniprobe were studied
      prospectively. The results of this imaging were compared with the histologic
      findings in resected specimens. RESULTS: Although the accuracy of the miniprobe
      in categorizing submucosal invasion into three subclasses (SM1, invasion limited
      to the upper third; SM2, limited to the middle third; SM3, limited to the lower
      third) was low (37.1%; 13/35), the accuracy in differentiation between < or = SMI
      (M and SMI) and > or = SM2 (SM2, SM3, MP, and S) was 85.7 % (30/35). CONCLUSIONS:
      The miniprobe can be useful for therapeutic decision-making in submucosal
      invasive colorectal cancer.

PMID- 11293757
TI  - The safety and feasibility of percutaneous endoscopic gastrostomy placement by a
      single physician.
AB  - BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) has become
      the procedure of choice for enteral feeding. However, the procedure usually
      requires two physicians, which makes it more difficult to schedule than
      procedures performed by a single physician. We investigated whether PEG insertion
      by a single physician could be done with the same safety and feasibility as by
      two physicians. PATIENTS AND METHODS: This study involved 339 consecutive
      patients who were referred for PEG. The same single physician, together with a
      nurse, performed the procedure in all patients, instead of the usual procedure
      performed by two physicians. Followed up of the patients for 1 month after the
      procedure was done. RESULTS: Minor complications occurred in 35 patients (10.3%),
      most frequently self-extubation and skin irritation. Eight patients (2.4%) had
      severe complications, including apnea in two, and wound infection that needed
      systemic antibiotics in another three patients. Three patients needed surgery
      because of peritonitis as a consequence of the procedure. There was no mortality
      in the first 48 hours after the procedure and only one patient death could be
      attributed to the procedure. CONCLUSIONS: The insertion of PEG by a single
      experienced physician is as safe as that described in the literature with two
      physicians. This should not replace the traditional approach with two physicians,
      but should be reserved for special situations when only one physician is
      available.

PMID- 11293758
TI  - Thyroid function, thyroid immunoglobulin status, and urinary iodine excretion
      after enteral contrast-agent administration by endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to examine the occurrence of
      clinically relevant changes in thyroid function after enteral administration of
      contrast agent by endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS
      AND METHODS: In this study 70 patients without a history of thyroid disease who
      had not recently undergone thyroid-specific or thyroid-influencing therapy were
      examined. Patients were examined on two or three occasions using a standardized
      questionnaire regarding symptoms of hypothyroidism and hyperthyroidism. The
      parameters of thyroid function (TT3, TT4, FT4, thyroid-stimulating hormone (TSH))
      and urinary iodine excretion were measured on day 0 and on day 21 post-ERCP, and
      in 23 patients additionally on day 42 post-ERCP. Based on ultrasonographic
      results, four groups differing in thyroid morphology were distinguished. RESULTS:
      The data show that an average amount of only 4.7 g of enterally applied iodine is
      associated with a lasting decrease of TSH, especially in patients with enlarged
      organs with nodular transformation. As far as TT3 is concerned, there was a
      significant increase in all patient groups; regarding FT4 we only observed a
      marked increase in the group with enlarged, nodular thyroid glands. There was a
      notable increase in urinary iodine excretion on day 21, and a further increase on
      day 42 post-ERCP. Clinical symptoms of hyperthyroidism did not occur.
      CONCLUSIONS: We conclude that before administration of iodine-containing contrast
      agent for ERCP in patients without a history of thyroid disease, thyroid
      ultrasonographic examination, rather than TSH measurements, should be performed,
      in order to identify patients already at risk for hyperthyroidism before
      diagnostic enteral contrast-medium application.

PMID- 11293759
TI  - A novel approach to endoscopic colorectal mucosal resection using a three-channel
      outer tube and multiple forceps: an experimental assessment.
AB  - BACKGROUND AND STUDY AIMS: Colorectal endoscopic mucosal resection (EMR) has
      limitations both anatomically and technically when it is done using the
      conventional snare wire method. The aim of this study was to develop a new method
      and instrument for colorectal EMR. METHODS: A total of 21 EMR procedures were
      done using ten surgical specimens. Saline was injected into the normal submucosa
      of freshly resected colorectal specimens to prepare a pseudotumor. EMR was
      performed experimentally by employing a three-channel outer tube with three
      forceps and a colonoscope with a needle-type precutting knife. This method was
      assessed in terms of safety and the size of the resected specimens. RESULTS:
      Perforation occurred only twice in the initial stage of this study. The size of
      the specimens resected by EMR was 28-39 mm (long diameter 34.8+/-3.11), by 22-28
      mm (short diameter 25.8+/-2.07). CONCLUSION: This method can achieve safety and
      en bloc mucosal resection to the submucosal layer. This novel approach may be
      promising for clinical application as a new form of endoscopic surgery.

PMID- 11293760
TI  - Argon plasma coagulation in the treatment of Barrett's high-grade dysplasia and
      in situ adenocarcinoma.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic therapy of high-grade dysplasia (HGD) and
      superficial adenocarcinoma associated with Barrett's esophagus (BE), using Nd:YAG
      laser, KTP laser, or photodynamic therapy (PDT), has been reported to be
      effective in a curative role. Argon plasma coagulation (APC) appears to be
      effective in the eradication of nondysplastic Barrett's mucosa, but no results
      are available in the management of early neoplasms complicating BE. We report our
      initial experience in the application of APC in this indication. PATIENTS AND
      METHODS: Ten patients (mean age 74.2) with histologically proven HGD (n = 7) or
      in situ adenocarcinoma (n = 3) associated with BE (mean length 6 cm) and unfit
      for surgery were treated using APC and high-dose omeprazole (40 mg daily) until
      squamous re-epithelialization or complete eradication of the initially apparent
      lesions. Endoscopic follow-up was maintained at every 3 months. RESULTS: Complete
      eradication of HGD and in situ adenocarcinoma was achieved after a mean number of
      3.3+/-1.5 APC sessions in 8/10 patients (80%). The eight patients with complete
      clearance of the neoplastic areas did not show any evidence of local recurrence
      during a median follow-up of 24 months (range 12-36 months). One patient with
      initial HGD had persistence of HGD 30 months after initial diagnosis, and one
      patient progressed to invasive adenocarcinoma after failure of APC and PDT.
      CONCLUSIONS: APC is safe and effective in the management of HGD and in situ
      adenocarcinoma associated with BE, and might represent an interesting alternative
      in selected patients who are not candidates for surgery.

PMID- 11293761
TI  - Cap polyposis of the colon and rectum: an analysis of endoscopic findings.
AB  - BACKGROUND AND STUDY AIMS: Because of the rarity of cap polyposis of the colon
      and rectum, the endoscopic features of this condition have not been specified to
      date. The aim of this study is to characterize the endoscopic features of cap
      polyposis. PATIENTS AND METHODS: The diagnosis of cap polyposis was established
      by histologic findings in specimens obtained endoscopically or surgically from
      four patients. Colonoscopic findings in the four patients were retrospectively
      reviewed. RESULTS: The endoscopic features were divided into semipedunculated
      type (three patients) and flat-topped protruding type (one patient). In the
      semipedunculated type, the polyps were characterized by reddish protrusions of
      various configurations with eroded surface in the rectosigmoid colon. In the
      remaining patient, all the lesions were flat protrusions with a reddish central
      depression. The polyps of both types became smaller in size and fewer in number
      at the proximal part of the sigmoid colon. Multiple white specks were observed in
      the intervening mucosa in all four patients. CONCLUSIONS: The prominence of the
      polyps at the distal part of the colon and rectum and multiple white specks in
      the intervening mucosa seem to be the additional endoscopic features suggestive
      of cap polyposis.

PMID- 11293762
TI  - Laparoscopic findings in primary sclerosing cholangitis.
AB  - BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a cholestatic
      disease characterized by segmental narrowing and dilatation of bile ducts. Few
      studies have been performed on the laparoscopic findings associated with this
      disease, and the present study was intended to assess the usefulness of
      laparoscopy for the diagnosis and staging of PSC. PATIENTS AND METHODS: Six
      patients were examined by laparoscopy with liver biopsy. Repeated laparoscopy was
      performed in three patients. RESULTS: Laparoscopy revealed coarse surface
      irregularity and discoloration. Surface irregularity was classified into four
      grades: smooth, shallowly depressed, undulated, and nodular. The affected area
      showed whitish yellow discoloration. The discolored area was demonstrated as a
      poorly stained area by intravenous injection of indocyanine green (ICG). Lobular
      markings became apparent because of the yellow color change in the portal tract,
      resulting in a leopardskin-like appearance. Lymph-vessel dilatation was seen in
      advanced stages. Repeated laparoscopy of a patient without treatment demonstrated
      a progression from a smooth surface to a shallow depression with leopardskin-like
      markings. On the other hand, the two patients treated with immunosuppressive
      agents showed improvement of liver swelling and disappearance of the leopardskin
      like markings and lymph-vessel dilatation. CONCLUSIONS: Laparoscopy may provide
      useful information for the diagnosis and staging of PSC.

PMID- 11293763
TI  - Endoscopic mucosal resection: an overview of the value of different techniques.

PMID- 11293764
TI  - Electronic documentation in endoscopy: present status and future perspectives
      from a company standpoint.
AB  - At the beginning of the development of endoscopic information systems all
      companies were technology-oriented. Today, we see a change from technology to
      content orientation, the same development which is seen in internet technology.
      In future systems, it will not be the software that makes a difference but the
      contents. Contents means not only patient data but also algorithms for feature
      extraction within large databases with reference images, for example [20]. The
      automatic recognition of features, such as a complication rate that is too high
      or a correlation of a certain disease with an endoscopic finding, will be part of
      a content-based approach. It means that content will also be the knowledge base
      which has to be developed for future systems. The system of the future will be
      much more intelligent and less software technology-oriented.

PMID- 11293765
TI  - Natural history of sigmoid colon cancer: report of a patient observed for 4
      years.
AB  - We report a case of sigmoid colon cancer that was left untreated for a period of
      4 years, because the patient declined treatment. A 59-year-old man was found to
      have an early carcinoma of the sigmoid colon measuring approximately 12 mm in
      diameter. The lesion, initially a flat cancer, increased in height and became
      sessile 4 months later. Subsequently, the central portion of the lesion became
      ulcerated, leaving an elevated ring along its periphery. The lesion eventually
      evolved into an ulcerated, invasive cancer. This sequence has not been observed
      with colonoscopy before.

PMID- 11293766
TI  - Percutaneous cholangioscopic bilioenterostomy for unreconstructed segmental bile
      duct after hepatobiliary resection for hilar cholangiocarcinoma.
AB  - During a major hepatectomy, inadvertent ligation of the major segmental bile-duct
      branch of the liver remnant is a serious complication. We experienced this
      serious complication of inadvertent ligation of the bile-duct branch, which
      should be anastomosed to the jejunal loop, during a left hepatic trisegmentectomy
      with total caudate lobectomy for a hilar cholangiocarcinoma. A percutaneous
      transhepatic bilioenteric connection was then created, modifying an endoscopic
      ureteroneocystostomy technique, between the ligated segmental bile duct and the
      jejunal loop. In this procedure, we used two cholangioscopes; one was introduced
      through the percutaneous transhepatic drainage route, the other was introduced
      through an enterostomy which was made during the surgery for postoperative
      enteral feeding; we also used a transjugular intrahepatic portosystemic shunt
      (TIPS) kit under fluoroscopic guidance. We present here our technique of
      percutaneous transhepatic bilioenterostomy.

PMID- 11293767
TI  - Argon plasma endoscopic section of biliary metallic prostheses.
AB  - We report our recent experience of using argon plasma to endoscopically cut
      biliary Wallstent prostheses in these patients. The first patient had a bleeding
      duodenal ulceration caused by the impaction of the prosthesis meshes whereas the
      second patient had an ill-positioned biliary stent with impaction into the
      opposite duodenal wall. Both prostheses were shortened using argon plasma. In the
      third patient, the lower extremity of a obstructed biliary Wallstent was
      positioned in the third duodenum preventing its endoscopic catheterization. After
      shortening using argon plasma, a new plastic stent could be inserted to allow
      drainage. The outcomes in these cases demonstrate the feasibility of
      endoscopically shortening metallic Wallstents after release using argon plasma.

PMID- 11293768
TI  - Use of multiple self-expanding metal stents to treat corrosive induced esophageal
      strictures.

PMID- 11293769
TI  - Virtual colonoscopy.

PMID- 11293770
TI  - Sigmoidoscopically induced pneumatosis cystoides coli in Crohn's disease
      manifested by collar subcutaneous emphysema.

PMID- 11293771
TI  - Laparoscopic partial hepatectomy for inflammatory pseudotumor of the liver.

PMID- 11293772
TI  - Endoscopic removal of a perforating toothpick.

PMID- 11293773
TI  - Rupture of diaphragm involving herniated viscera following a blunt trauma
      diagnosed by gastrofiberoscopy.

PMID- 11293774
TI  - Verrucous carcinoma of the esophagus.

PMID- 11293775
TI  - Small neuroendocrine carcinoma of the rectum entirely covered by an adenomatous
      component.

PMID- 11293776
TI  - Mouse genomic imaging laboratories: an opportunity for radiology to move from the
      bedside to the bench.

PMID- 11293777
TI  - Improving clinical histories on radiology requisitions.
AB  - PURPOSE: The Health Care Financing Administration (HCFA) regards billing for
      radiologic examinations without an appropriate indication as unlawful, and both
      the referring physician and the radiologist are liable. HCFA regulations are
      interpreted as requiring that all requisitions for radiologic examinations
      include a current diagnosis and appropriate indication for the study. The purpose
      of this investigation was to determine the rates at which requisitions currently
      meet these criteria and to assess the effectiveness of a simple intervention
      designed to improve them. MATERIALS AND METHODS: One hundred fifty consecutive
      chest radiography requisitions were examined to determine the rate at which
      current diagnoses and appropriate indications were present. An intervention was
      then implemented that included a month-long effort to inform referring physicians
      and radiologists of HCFA regulations, followed by a 1-week period during which
      requested examinations were not performed unless accompanied by a clinical
      diagnosis and appropriate indication. Another 150 consecutive chest radiography
      requisitions were then assessed to determine the effect of the intervention. A 3
      month follow-up sample of a third set of 150 consecutive requisitions was then
      obtained. RESULTS: The intervention produced a 69% decrease in the rate at which
      current diagnoses were missing from requisitions, and a 61% decrease in the
      corresponding rate for appropriate indications. Both results are significant with
      chi2 analysis at the P = .001 level. After 3 months with no additional
      intervention, rates decayed back toward baseline, with only a 35% remaining
      decrease for current diagnosis and an 18% decrease for appropriate indication.
      CONCLUSION: The intervention performed in this study significantly reduces the
      rate of noncompliance with HCFA regulations. However, this improvement decays
      over time if it is not reinforced.

PMID- 11293778
TI  - Gaze dwell times on acute trauma injuries missed because of satisfaction of
      search.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to determine whether
      satisfaction of search (SOS) errors in patients with multiple traumas are caused
      by faulty visual scanning, faulty recognition, or faulty decision making.
      MATERIALS AND METHODS: A series of radiographs were obtained in patients with
      multiple traumas. Radiologists interpreted each series under two experimental
      conditions: when the first radiograph in the series included a fracture, and when
      it did not. In the first experiment, the initial radiographs showed nondisplaced
      fractures of the extremities (minor fractures); in the second experiment, the
      initial radiographs showed abnormalities of greater clinical importance (major
      fractures). Each series also included a radiograph with a subtle (test) fracture
      and a normal radiograph on which detection accuracy was measured. In each
      experiment, gaze dwell time was recorded as 10 radiologists reviewed images from
      10 simulated cases of multiple trauma. RESULTS: An SOS effect could be
      demonstrated only in the second experiment. Analysis of dwell times showed that
      search on subsequent radiographs was shortened when the initial radiograph
      contained a fracture; however, the errors were not based on faulty scanning.
      CONCLUSION: The SOS effect in musculoskeletal trauma is not caused by faulty
      scanning. Demonstration of an SOS effect on test fractures with major but not
      minor additional fractures suggests that detection of other fractures is
      inversely related to the severity of the detected fracture.

PMID- 11293779
TI  - Evaluation of competence in the interpretation of chest radiographs.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine relative
      rates of missed diagnoses for radiologists as a measure of competence in
      interpreting chest radiographs. MATERIALS AND METHODS: Cases involving differing
      interpretations of chest radiographs were collected from January 1994 through
      December 1999 by faculty (chest and nonchest radiology specialists) in an
      academic radiology department. A quarterly peer-review process designated cases
      months after the fact, and anonymously, as no miss or as class I
      (nondiagnosable), class II (very difficult diagnosis), class III (should be
      diagnosed most of time), or class IV (should almost always be diagnosed) missed
      diagnoses. The rates and classes of missed diagnoses were compared among chest
      faculty and for the nonchest radiology specialists as a group. RESULTS: Chest
      radiologists read 184,977 studies, and nonchest radiologists read 300,684
      studies. Of these, 243 missed diagnoses were classified (classes I and II, 184
      cases; class III, 50; and class IV, nine). No difference was detected in the rate
      of class III and IV misses among chest faculty, but nonchest faculty had
      significantly more class III (P = .022) and class IV misses (P = .016).
      CONCLUSION: Random sampling of differing interpretations can yield a relative
      rate of missed diagnoses for radiologists. No difference was detected in
      clinically important misses (ie, classes III and IV) among chest radiologists,
      but a statistically significantly higher rate of seemingly obvious misdiagnoses
      was found for nonchest specialty radiologists. Potential biases may have
      influenced this analysis, including disease prevalence, sampling, clinical
      factors, observer variability, and truth-in-diagnosis.

PMID- 11293780
TI  - Role of US-guided fine-needle aspiration with on-site cytopathologic evaluation
      in management of nonpalpable breast lesions.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy
      of ultrasound (US)-guided fine-needle aspiration (FNA), with radiographic follow
      up or surgical excision, in conjunction with on-site cytopathologic support in
      the management of nonpalpable breast lesions. MATERIALS AND METHODS: The findings
      of 266 consecutive mammographically or sonographically identified, nonpalpable
      lesions (228 patients) that underwent US-guided FNA were examined
      retrospectively. Clustered microcalcifications did not undergo biopsy with this
      method. Patients who underwent follow-up excisional biopsy or mammography with a
      duration of at least 24 months were included in the study. RESULTS: In all, 117
      lesions met criteria for inclusion, of which 85 (73%) were diagnosed as benign at
      cytopathologic evaluation and underwent mammographic follow-up of at least 24
      months (range, 24-67 months; mean, 36 months). Thirty-two lesions (27%) had
      either malignant or atypical cytopathologic findings, for which surgery was
      recommended. Eleven (9%) of the 32 had malignant cytopathologic findings from
      initial US-guided FNA, which were confirmed at surgical excision. The remaining
      21 lesions (18%) were diagnosed as atypical on the basis of US-guided FNA
      results. Of these, 18 lesions underwent excisional biopsy: Two were diagnosed as
      carcinoma (not otherwise specified), and 16 were diagnosed with a variety of
      benign disorders. The remaining three patients with atypical lesions chose
      mammographic follow-up rather than surgical diagnosis, and their conditions have
      remained stable for more than 24 months. Of the 85 benign cases, one changed
      during follow-up (12 months) and underwent repeat biopsy, with malignancy noted.
      The sensitivity of US-guided FNA in identifying malignant lesions was 93% (13 of
      14), and the specificity of a benign finding was 100% (102 of 102). The positive
      and negative predictive values of US-guided FNA supported by on-site
      cytopathologic evaluation were 100% (13 of 13) and 99% (102 of 103),
      respectively. CONCLUSION: Supported by appropriately trained on-site
      cytopathologists and in conjunction with follow-up mammography, US-guided FNA
      appears to be efficacious in the management of patients with abnormal
      radiographic findings. It is quick, relatively inexpensive, and minimally
      invasive, and, in the presence of competent cytopathologists, should be the
      modality of choice.

PMID- 11293781
TI  - Continuous versus categorical data for ROC analysis: some quantitative
      considerations.
AB  - RATIONALE AND OBJECTIVES: Several authors have encouraged the use of a quasi
      continuous rating scale for data collection in receiver operating characteristic
      (ROC) curve analysis of diagnostic modalities, rather than rating scales based on
      five to seven ordinal categories or levels of suspicion. Although many
      investigators have gone over to this method, a discussion of the issues
      continues. The present work provides a quantitative analysis from the viewpoint
      of measurement science. MATERIALS AND METHODS: A simple model of the effect of
      data discretization or quantization on the measurement of the variance of noisy
      data was developed. Then Monte Carlo simulations of multiple-reader, multiple
      case ROC experiments were performed and analyzed in terms of components-of
      variance models to investigate the effect of data quantization in that more
      complex setting. RESULTS: For single-reader studies, discretization into five
      categories can reduce the precision of ROC measurements by a large amount. The
      effect may be attenuated in multireader studies. CONCLUSION: More precise
      measurements of diagnostic detection performance and thus more efficient use of
      resources are served by good measurement methods. These are promoted by the use
      of a quasi-continuous rating scale in ROC studies.

PMID- 11293782
TI  - Interreader variability and predictive value of US descriptions of solid breast
      masses: pilot study.
AB  - RATIONALE AND OBJECTIVES: This study evaluated the specificity of ultrasound (US)
      characteristics of solid breast lesions and the interreader variability in their
      interpretation. MATERIALS AND METHODS: In 61 patients, 70 sonographically visible
      solid masses, scheduled for biopsy because of findings from conventional imaging,
      were prospectively and sequentially accrued for evaluation. Three readers
      interpreted the sonograms and described the solid masses in terms of established
      US characteristics. The specificity and positive predictive value (PPV) for each
      characteristic were calculated by comparing US findings with biopsy findings, and
      interreader variability was evaluated. Five assessment categories were developed
      to guide recommendations for patient care. The relative performance of each
      reader was assessed by measuring the PPV for each assessment category and by
      measuring the area under the receiver operating characteristic curve. RESULTS:
      The specificity and PPV were calculated for all characteristics and for each
      reader. The average specificities of the three readers for the most frequently
      used six characteristics were as follows: spiculation, 97%+/-5 (standard
      deviation); taller than wide, 91%+/-4; central shadowing, 77%+/-1; markedly
      hypoechoic, 86%+/-5; duct extension, 95%+/-5; and microlobulation, 84%+/-3
      (overall average specificity, 88.5%). The average PPVs for categories II-V were
      5%, 10%, 63%, and 94%, respectively. The readers' interpretations were similar
      and correlated well. CONCLUSION: The proposed US recommendation system is an
      accurate predictor of histologic findings. A sonographic classification lexicon
      should prove valuable.

PMID- 11293783
TI  - Pulmonary embolism: comparison of gadolinium-enhanced MR angiography with
      contrast-enhanced spiral CT in a porcine model.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to compare gadolinium
      enhanced magnetic resonance (MR) angiography with contrast material-enhanced
      computed tomography (CT) for the detection of small (4-5-mm) pulmonary emboli
      (PE), with a methacrylate cast of the porcine pulmonary vasculature used as the
      diagnostic standard. MATERIALS AND METHODS: In 15 anesthetized juvenile pigs,
      colored methacrylate beads (5.2 and 3.8 mm diameter-the size of segmental and
      subsegmental emboli in humans) were injected via the left external jugular vein.
      After embolization, MR angiographic and CT images were obtained. The pigs were
      killed, and the pulmonary arterial tree was cast in clear methacrylate, allowing
      direct visualization of emboli. Three readers reviewed CT and MR angiographic
      images independently and in random order. RESULTS: Forty-nine separate embolic
      sites were included in the statistical analysis. The mean sensitivity (and 95%
      confidence intervals) for CT and MR angiography, respectively, were 76% (68%-82%)
      and 82% (75%-88%) (P > .05); the mean positive predictive values, 92% (85%-96%)
      and 94% (88%-97%) (P > .05). In this porcine model, PE were usually seen as
      parenchymal perfusion defects (98%) with MR angiography and as occlusive emboli
      (100%) with CT. CONCLUSION: MR angiography is as sensitive as CT for the
      detection of small PE in a porcine model.

PMID- 11293784
TI  - NCI-funded small animal imaging programs. National Cancer Institute.

PMID- 11293785
TI  - Common mechanisms of Y chromosome evolution.
AB  - Y chromosome evolution is characterized by the expansion of genetic inertness
      along the Y chromosome and changes in the chromosome structure, especially the
      tendency of becoming heterochromatic. It is generally assumed that the sex
      chromosome pair has developed from a pair of homologues. In an evolutionary
      process the proto-Y-chromosome, with a very short differential segment, develops
      in its final stage into a completely heterochromatic and to a great extends
      genetically eroded Y chromosome. The constraints evolving the Y chromosome have
      been the objects of speculation since the discovery of sex chromosomes. Several
      models have been suggested. We use the exceptional situation of the neo-Y in
      Drosophila miranda to analyze the molecular process in progress involved in Y
      chromosome evolution. We suggest that the first steps in the switch from a
      euchromatic proto-Y-chromosome into a completely heterochromatic Y chromosome are
      driven by the accumulation of transposable elements, especially retrotransposons
      inserted along the evolving nonrecombining part of the Y chromosome. In this
      evolutionary process trapping and accumulation of retrotransposons on the proto-Y
      chromosome should lead to conformational changes that are responsible for
      successive silencing of euchromatic genes, both intact or already mutated ones
      and eventually transform functionally euchromatic domains into genetically inert
      heterochromatin. Accumulation of further mutations, deletions, and duplications
      followed by the evolution and expansion of tandem repetitive sequence motifs of
      high copy number (satellite sequences) together with a few vital genes for male
      fertility will then represent the final state of the degenerated Y chromosome.

PMID- 11293786
TI  - Molecular aspects of intron evolution in dynein encoding mega-genes on the
      heterochromatic Y chromosome of Drosophila sp.
AB  - Fertility genes on the heterochromatic Y chromosome of various Drosophila species
      are unique for several reasons. Most of them are megabase-sized. Their expression
      is restricted to premeiotic spermatocytes and often associated with unfolding of
      huge species-specific lampbrush loops. Molecular analysis of the orthologous
      dynein genes Dhc-Yh3, DhDhc7(Y) and DeDhc7(Y) on the Y chromosome of the three
      species D. melanogaster, D. hydei and D. eohydei, respectively, revealed that the
      megabase gene size as well as the species-specific morphology of the
      corresponding lampbrush loops kl-5, Threads and diffuse loops result from huge
      introns and their specific sequence composition, whereas the majority of all 20
      introns in each of the three genes is in a size of 45-72 bp. The loop-specifying
      introns are extreme exceptions due to extended assemblies of degenerated
      transposable elements and/or large clusters of satellite DNAs. Here we use
      sequence information from the complete intron sets of three orthologous Y
      chromosomal dynein genes to deduce a scenario for an evolutionary pathway leading
      to the megabase-sized genes on the heterochromatic Y chromosome of Drosophila.
      The obvious bias between very small and species-specific mega introns is
      explained as the result of an autocatalytic mode of intron growth. An initial
      coincidental hit by a single transposable element extends the size of a 50 bp
      intron for about two orders of magnitude and determines it for preferential
      extension by similar insertion events. This phase of continuous moderate growth
      is followed by rapid size enlargements by repeating amplifications generating
      extended clusters of satellite DNA. Size control by recombination, on the other
      hand, is suppressed in Drosophila males by achiasmatic meiosis.

PMID- 11293787
TI  - Evolution of DNA in heterochromatin: the Drosophila melanogaster sibling species
      subgroup as a resource.
AB  - The Drosophila melanogaster species subgroup is a closely-knit collection of
      eight sibling species whose relationships are well defined. These species are too
      close for most evolutionary studies of euchromatic genes but are ideal to
      investigate the major changes that occur to DNA in heterochromatin over short
      periods during evolution. For example, it is not known whether the locations of
      genes in heterochromatin are conserved over this time. The 18S and 28S ribosomal
      RNA genes can be considered as genuine heterochromatic genes. In D. melanogaster
      the rRNA genes are located at two sites, one each on the X and Y chromosome. In
      the other seven sibling species, rRNA genes are also located on the sex
      chromosomes but the positions often vary significantly, particularly on the Y.
      Furthermore, rDNA has been lost from the Y chromosome of both D. simulans and D.
      sechellia, presumably after separation of the line leading to present-day D.
      mauritiana. We conclude that changes to chromosomal position and copy number of
      rDNA arrays occur over much shorter evolutionary timespans than previously
      thought. In these respects the rDNA behaves more like the tandemly repeated
      satellite DNAs than euchromatic genes.

PMID- 11293788
TI  - Paralogous stellate and Su(Ste) repeats: evolution and ability to silence a
      reporter gene.
AB  - The X-linked Stellate repeats, encoding a putative regulatory subunit of protein
      kinase CK2, are expressed in XO male testes. The Y-linked, testes-expressed
      paralogous Su(Ste) repeats are thought to be suppressors of Stellate
      transcription. The unique, testis-expressed euchromatic gene was suggested to be
      an ancestor of the both types of amplified paralogous repeats. A Su(Ste)-like
      orphon was localized on a Y chromosome, outside of the Su(Ste) cluster. Several
      diagnostic molecular markers peculiar for the both types of diverged Stellate and
      Su(Ste) units were detected in the orphon sequence. The orphon was suggested to
      be a close relative of the immediate ancestor of both types of paralogous repeats
      which initiated evolution on the Y chromosome. Selection pressure on the level of
      translation was shown as a driving force in the evolution of Su(Ste) repeats,
      which are considered as more ancient derivatives of the ancestor euchromatic gene
      than Stellate repeats. In a vicinity of 12E Stellate cluster the undamaged,
      recently originated euchromatic Stellate orphon was found at 12D, providing the
      poly(A) signal for the bendless gene. P-element mediated transformations reveal
      that the fragments of cloned Stellate and Su(Ste) clusters are able to induce
      variegation of a reporter mini-white gene. The observed variegation phenomenon
      has peculiar features: a significant increase of trans-activation of a reporter
      mini-white gene in homozygous state; absence of effects of several conventional
      modifiers of position effect variegation (PEV) and independence of a severity of
      variegation on a distance between insertion and centromere region.

PMID- 11293789
TI  - A trans-activator on the Drosophila Y chromosome regulates gene expression in the
      male germ line.
AB  - The Y chromosome of Drosophila melanogaster accounts for approximately 13% of a
      normal male genome and is entirely heterochromatic. It carries six genes required
      exclusively for spermatogenesis. Here we report a novel activity of the Y
      chromosome that regulates gene expression in primary spermatocytes. By examining
      the expression of a reporter gene in X/Y and X/O males, we show that a specific
      region of the Y long arm carries a trans-activator that regulates transcription
      in spermatogenesis. In the absence of the Y trans-activator, the level of the
      reporter expression is greatly reduced in primary spermatocytes and the
      expression pattern is restricted to young primary spermatocytes. Further analysis
      shows that the Y trans-activator is dispersed in the h1-h10 region on the Y long
      arm and is functionally redundant, indicating involvement of the repetitive
      sequences on the Y chromosome. In addition, the Y trans-activator appears to act
      in a tissue-specific manner, functioning only in the male germ line. We propose
      that the Y trans-activator plays an important role in regulating gene expression
      during spermatogenesis.

PMID- 11293790
TI  - Versatility of conviction: heterochromatin as both a repressor and an activator
      of transcription.

PMID- 11293791
TI  - Drosophila telomeric transgenes provide insights on mechanisms of gene silencing.
AB  - A significant fraction of most eukaryotic genomes is packaged into chromatin that
      is not permissive for gene expression. This silent chromatin is typically located
      near centromeres and telomeres and has fascinated scientists for more than 70
      years, yet many questions remain unanswered. Part of the difficulties in studying
      silent chromatin at the molecular level is the repetitive nature of the DNA
      sequences in these regions. To overcome this problem, Drosophila stocks carrying
      in vitro designed transgenes inserted within silent chromatin have been
      generated. Molecular analysis of these transgenes has shed light on the nature of
      the chromatin structure within these regions and provided insights on the
      mechanisms of gene silencing. This review will focus on recent studies using
      telomeric transgenes. The results from these studies suggest that nuclear
      organization plays a role in gene silencing and that silencing is the result of a
      block early in the process of transcription initiation.

PMID- 11293792
TI  - Introduction. Shedding new light on the dark corners of the nucleus.

PMID- 11293793
TI  - Parental imprinting in Drosophila.
AB  - Genetic imprinting is a form of epigenetic silencing. But with a twist. The twist
      is that while imprinting results in the silencing of genes, chromosome regions or
      entire chromosome sets, this silencing occurs only after transmission of the
      imprinted region by one sex of parent. Thus genetic imprinting reflects
      intertwined levels of epigenetic and developmental modulation of gene expression.
      Imprinting has been well documented and studied in Drosophila, however, these
      studies have remained largely unknown due to nothing more significant than
      differences in terminology. Imprinting in Drosophila is invariably associated
      with heterochromatin or regions with unusual chromatin structure. The imprint
      appears to spread from imprinted centers that reside within heterochromatin and
      these are, seemingly, the only regions that are normally imprinted in Drosophila.
      This is significant as it implies that while imprinting occurs in Drosophila, it
      is generally without phenotypic consequence. Hence the evolution of imprinting,
      at least in Drosophila, is unlikely to be driven by the function of specific
      imprinted genes. Thus, the study of imprinting in Drosophila has the potential to
      illuminate the mechanism and biological function of imprinting, and challenge
      models based solely on imprinting of mammalian genes.

PMID- 11293794
TI  - Drosophila telomere transposons: genetically active elements in heterochromatin.
AB  - In Drosophila two non-LTR retrotransposons, HeT-A and TART, offer a novel
      experimental system for the study of heterochromatin. These elements, found only
      in heterochromatin, form Drosophila telomeres by repeated transposition onto
      chromosome ends. Their transposition yields arrays of repeats larger and more
      irregular than the repeats produced by telomerase; nevertheless, the
      transpositions are, in principle, equivalent to the telomere-building action of
      telomerase. The identification of the HeT-A promoter has given the first view of
      the molecular structure of a promoter active in heterochromatin. These telomere
      specific elements are unusual in having a large amount of non-coding sequence.
      Like many other heterochromatic sequences, the HeT-A non-coding sequence has a
      repetitive organization strongly conserved within the species, although the
      sequence itself can undergo significant change between species (a typical example
      of concerted evolution). Such heterochromatic sequences could be important for
      the cell, perhaps as docking stations for essential proteins.

PMID- 11293795
TI  - Impact of multiple insertions of two retroelements, ZAM and Idefix at an
      euchromatic locus.
AB  - Transposable elements represent a large fraction of eukaryotic genomes and they
      are thought to play an important role in chromatin structure. ZAM and Idefix are
      two LTR-retrotransposons from Drosophila melanogaster very similar in structure
      to vertebrate retroviruses. In all the strains where their distribution has been
      studied, ZAM appears to be present exclusively in the intercalary heterochromatin
      while Idefix copies are mainly found in the centromeric heterochromatin with very
      few copies in euchromatin. Their distribution varies in a specific strain called
      RevI in which the mobilization of ZAM and Idefix is highly induced. In this
      strain, 15 copies of ZAM and 30 copies of Idefix are found on the chromosomal
      arms in addition to their usual distribution. Amongst the loci where new copies
      are detected, a hotspot for their insertion has been detected at the white locus
      where up to four elements occurred within a 3-kb fragment at the 5' end of this
      gene. This property of ZAM and Idefix to accumulate at a defined site provides an
      interesting paradigm to bring insight into the effect exerted by multiple
      insertions of transposable elements at an euchromatic locus.

PMID- 11293797
TI  - Reaching for new heitz.

PMID- 11293796
TI  - Control of telomere elongation and telomeric silencing in Drosophila
      melanogaster.
AB  - Chromosome length in Drosophila is maintained by the targeted transposition of
      two families of non-LTR retrotransposons, HeT-A and TART. Although the rate of
      transposition to telomeres is sufficient to counterbalance loss from the
      chromosome ends due to incomplete DNA replication, transposition as a mechanism
      for elongating chromosome ends raises the possibility of damaged or deleted
      telomeres, because of its stochastic nature. Recent evidence suggests that HeT-A
      transposition is controlled at the levels of transcription and reverse
      transcription. HeT-A transcription is found primarily in mitotically active
      cells, and transcription of a w+ reporter gene inserted into the 2L telomere
      increases when the homologous telomere is partially or completely deleted. The
      terminal HeT-A array may be important as a positive regulator of this activity in
      cis, and the subterminal satellite appears to be an important negative regulator
      in cis. A third chromosome modifier has been identified that increases the level
      of reverse transcriptase activity on a HeT-A RNA template and greatly increases
      the transposition of HeT-A. Thus, the host appears to play a role in
      transposition of these elements. Taken together, these results suggest that
      control of HeT-A transposition is more complex than previously thought.

PMID- 11293798
TI  - Searching for a common centromeric structural motif: Drosophila centromeric
      satellite DNAs show propensity to form telomeric-like unusual DNA structures.
AB  - The molecular basis of centromere formation in a particular chromosomal region is
      not yet understood. In higher eukaryotes, no specific DNA sequence is required
      for the assembly of the kinetochore, but similar centromeric chromatins are
      formed on different centromere DNA sequences. Although epigenesis has been
      proposed as the main mechanism for centromere specification, DNA recognition must
      also play a role. Through the analysis of Drosophila centromeric DNA sequences,
      we found that dodeca satellite and 18HT satellite are able to form unusual DNA
      structures similar to those formed by telomeric sequences. These findings suggest
      the existence of a common centromeric structural DNA motif which we feel merits
      further investigation.

PMID- 11293800
TI  - Essential genes in autosomal heterochromatin of Drosophila melanogaster.
AB  - We are taking two approaches to understanding the structure, function and
      regulation of essential genes within Drosophila heterochromatin. In the first, we
      have undertaken a genetic and molecular characterization of essential genes
      within proximal 3L heterochromatin. The expression of such 'resident' genes
      within a heterochromatic environment is paradoxical and poorly understood, given
      that the same environment can inactivate euchromatic sequences (position effect
      variegation, or PEV). A second approach involves the study of the local
      chromosomal environment of heterochromatic (het) genes, as assayed both
      biochemically, and via the effects of genetic modifiers of PEV, the latter being
      putative components important for het gene expression. Our results to date
      suggest that the three most proximal genes in 3L heterochromatin have key roles
      in development, and indicate strong effects of combinations of genetic modifiers
      of PEV on het gene expression.

PMID- 11293799
TI  - On the roles of heterochromatin and euchromatin in meiosis in drosophila: mapping
      chromosomal pairing sites and testing candidate mutations for effects on X-Y
      nondisjunction and meiotic drive in male meiosis.
AB  - Mapping of pairing sites involved in meiotic homolog disjunction in Drosophila
      has led to conflicting hypotheses about the nature of such sites and the role of
      heterochromatin in meiotic pairing. In the female-specific distributive system,
      pairing regions appear to be exclusively heterochromatic and map to broad regions
      encompassing many different sequences. In male meiosis, autosomal pairing sites
      appear to be distributed broadly within euchromatin but to be absent from
      heterochromatin, whereas the X-pairing site maps in the centric heterochromatin.
      The X site has been shown to coincide with the intergenic spacer (IGS) repeats
      within the rDNA arrays shared between the X and Y. It has not been clear whether
      the heterochromatic location of this pairing site has any significance. A novel
      assay for genic modifiers of X-Y chromosome pairing was developed based on the
      intermediate nondisjunction levels observed in males whose X chromosome lacks the
      native pairing site but contains two transgenic insertions of single rDNA genes.
      This assay was used to test several mutations in Su(var) (Suppressor of position
      effect variegation), PcG (Polycomb-Group) recombination defective, and repair
      defective genes. No strong effects on disjunction were seen. However, the tests
      did uncover several mutations that suppress or enhance the meiotic drive
      (distorted X-Y recovery ratio) that accompanies X-Y pairing failure.

PMID- 11293801
TI  - Chromosomally-induced meiotic drive in Drosophila males: checkpoint or fallout?
AB  - In male Drosophila melanogaster, anomalies in sex chromosome pairing at meiosis
      often lead to complete or partial sperm dysfunction. This observation has led to
      the suggestion that defects in either the efficiency or configuration of
      chromosome pairing at metaphase trigger a checkpoint mechanism that leads to the
      elimination of meiotic products. Here, we discuss this model in consideration of
      recent observations on the conservation of metaphase checkpoint components in
      male meiosis, and on the phenotype of new alleles of the male-specific meiotic
      mutant teflon. Based on these observations, we propose an alternative hypothesis
      for the cause of sperm dysfunction in cases of chromosomal sterility and drive.
      We suggest that disruption of the prophase compartmentalization of sex chromatin,
      rather than abnormal pairing at metaphase, may be the causative defect. Such
      disruption may occur as a result of perturbations in sex chromosome pairing, or
      by translocations involving autosomal and sex chromatin. We discuss how this
      hypothesis may account for previously described examples chromosomal causes of
      meiotic drive and sterility in Drosophila.

PMID- 11293802
TI  - Peripheral neuropathy and antiretroviral drugs.
AB  - Patients treated with nucleoside analogue reverse transcriptase inhibitors
      (NRTIs) develop a varying degree of myopathy or neuropathy after long-term
      therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl)
      and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU)
      cause neuropathy or myopathy and lactic acidosis. The tissue distribution of
      phosphorylases responsible for phosphorylation of NRTIs relates to their
      selective tissue toxicity. The myopathy is characterized by muscle wasting,
      myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful,
      sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible
      for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated
      with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA
      depletion, deficiency of COX (complex IV), intracellular fat accumulation, high
      lactate production and marked phosphocreatine depletion, as determined with in
      vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or
      cultured cells treated with NRTIs develop neuropathy, myopathy, or cell
      destruction with similar changes in the mitochondria. There is evidence that the
      NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT,
      ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine
      triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In
      contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for
      thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA
      causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction
      has an influence on the clinical application of these agents, especially at high
      doses and when combined. They have produced in humans a new category of acquired
      mitochondrial toxins that cause clinical manifestations resembling the genetic
      mitochondrial disorders.

PMID- 11293803
TI  - HIV-associated neuropathies: role of HIV-1, CMV, and other viruses.
AB  - The role of the human immunodeficiency virus (HIV) and other viruses in the
      development of neuropathies associated with HIV infection is controversial.
      Distal symmetric polyneuropathy (DSP), the most common subtype of HIV-associated
      neuropathy, is characterized by an abundance of reactive macrophages within the
      peripheral nerve, but HIV replication is limited to a small percentage of the
      macrophages. Thus, the pathological destruction may be mediated by pro
      inflammatory signals amplified by activated glial elements within the nerve,
      similar to the proposed mechanism of damage caused by HIV within the central
      nervous system. In contrast, in mononeuropathy multiplex (MM) and progressive
      polyneuropathy (PP), cytomegalovirus (CMV) replication in the peripheral nerve is
      consistently demonstrable, and this replication likely results in direct damage
      to the infected cells (neurons and glia). The rarest form of HIV-associated
      neuropathy, the diffuse infiltrative lymphocytosis syndrome (DILS), is
      characterized by an intense CD8+ T lymphocyte infiltration into the nerve and
      abundant HIV infection of macrophages. Finally, while other viruses (varicella
      zoster, herpes simplex) are associated with myelitis in HIV-infected individuals,
      there is little support for a role for these viruses in HIV-associated
      neuropathy.

PMID- 11293804
TI  - HIV neuropathy: insights in the pathology of HIV peripheral nerve disease.
AB  - HIV-associated neuropathies (HIV-N) have become the most frequent neurological
      disorder associated with HIV infection. The most common forms of HIV-N are the
      distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathies (ATN),
      disorders characterized mostly by sensory symptoms that include spontaneous or
      evoked pain that follow a subacute or chronic course. The main pathological
      features that characterize DSP and ATN include "dying back" axonal degeneration
      of long axons in distal regions, loss of unmyelinated fibers, and variable degree
      of macrophage infiltration in peripheral nerves and dorsal root ganglia. Marked
      activation of macrophages as well as the effect of pro-inflammatory cytokines
      appear to be the main immunopathogenic factors in DSP. Interference with DNA
      synthesis and mitochondrial abnormalities produced by nucleoside antiretrovirals
      have been hypothesized as pathogenic factors involved in ATN. The use of skin
      biopsy has become a useful tool in the evaluation of HIV-N. Reduction in fiber
      density, increased frequency of fiber varicosities and fiber fragmentation are
      prominent features of skin biopsies from patients with HIV-N. Other forms of HIV
      N include acute or chronic inflammatory polyneuropathies, uncommon disorders that
      may ocur during seroconversion or early stages of HIV infection. Opportunisitic
      infections, mostly associated with cytomegalovirus or herpes zoster virus
      infection occur in late stages of AIDS and produce characteristic clinical
      features such as mononeuritis multiple or radiculopathies.

PMID- 11293805
TI  - Contribution of cranial nerve ganglia to innervation of the walls of the rat
      external acoustic meatus.
AB  - The retrograde neuronal tracer, fluorogold, was used to determine the relative
      contributions of neurons in selected cranial nerve ganglia to the somatosensory
      innervation of the external acoustic meatus in the rat. Frozen sections from the
      trigeminal (semilunar), facial (geniculate), glossopharyngeal (superior petrosal)
      and vagal (jugular) nerve ganglia were examined by epifluoresence microscopy 10
      to 14 days after application of the tracer dye fluorogold to the superior,
      inferior, anterior and posterior walls of the external acoustic meatus. The
      anterior wall of the canal makes a large contribution to the trigeminal ganglion
      and a lesser contribution to the other 3 ganglia. The trigeminal ganglion is also
      a major recipient from the posterior wall with smaller contributions from that
      wall to the geniculate and vagal ganglia. The superior wall projects a relatively
      constant supply to all 4 ganglia while the inferior wall primarily relays to the
      trigeminal and geniculate ganglia sending smaller contributions to the vagal and
      glossopharyngeal ganglia. In conclusion, neurons in these 4 cranial nerve ganglia
      contribute an overlapping supply to the 4 walls of the external ear meatus, and
      there is no evidence of a preferential distribution of nerve supply from one
      particular ganglion or nerve to specific walls of the external acoustic meatus.

PMID- 11293806
TI  - Effect of alpha-tocopherol supplementation on the ultrastructural abnormalities
      of peripheral nerves in experimental diabetes.
AB  - Ultrastructural observations were made on myelinated fibers in the tibial nerves
      in order to investigate the beneficial effects of alpha-tocopherol administration
      in streptozotocin-diabetic rats. Male Wistar rats, aged 12 weeks and weighing
      between 250 g to 300 g were studied. Six onset control rats were used to obtain
      the baseline parameters for this strain and age. Further 3 groups--untreated
      diabetic animals, diabetic animals treated with alpha-tocopherol, and age-matched
      controls--were studied over a 3-month period. In the diabetic animal,
      administration of alpha-tocopherol resulted in a significant increase (p < 0.05)
      in total plasma vitamin E levels when compared with other groups. Myelinated
      fiber cross-sectional area (p < 0.05), axonal area (p < 0.01) and myelin sheath
      area (p < 0.05) were significantly less in the tibial nerve of diabetic animals
      than in age-matched controls, but not different from those of onset controls. In
      the alpha-tocopherol treated diabetic animals, the values for these parameters
      were intermediate without showing significant difference when compared with age
      matched controls and untreated diabetics. The "g" ratio (axon to fiber area) did
      not differ between any experimental groups. The number of large myelinated fibers
      were less in the untreated diabetic animals, but in the alpha-tocopherol-treated
      diabetics, the values were significantly higher (p < 0.05) than with untreated
      diabetics and were similar to those of age-matched controls. In conclusion, this
      ultrastructural study reiterated the fact that structural abnormalities of
      myelinated fibers occur in experimental diabetes and that alpha-tocopherol
      administration may be useful in preventing the development of these
      abnormalities.

PMID- 11293807
TI  - Epidemiology and clinical features of HIV-1 associated neuropathies.
AB  - Peripheral neuropathy is common in human immunodeficiency virus type-1 (HIV-1)
      infection. Peripheral neuropathies complicate all stages of the HIV-1 disease and
      cause considerable morbidity and disability in HIV-1 infected individuals and
      acquired immunodeficiency syndrome (AIDS) patients. Whereas symptomatic
      neuropathies occur in approximately 10% to 15% of HIV-1-infected patients
      overall, pathologic evidence of peripheral nerve involvement is present in
      virtually all end-stage AIDS patients. There are 6 major clinical types of HIV
      associated neuropathies that are regularly seen in large HIV-1 clinics. Distal
      sensory polyneuropathy (DSP) is the most common among the HIV-1-associated
      neuropathies. DSP generally occurs in later stages of HIV-1 infection and it
      follows an indolent and protracted clinical course. The dominant clinical
      features in DSP include distal pain, paresthesia and numbness in a typical length
      dependent fashion with proximal to distal gradient. Whereas toxic neuropathies-
      secondary to certain antiretroviral agents--are clinically similar to DSP, their
      temporal relation to neurotoxic medication helps distinguish them from other HIV
      1-associated neuropathies. DSP and toxic neuropathy may coexist in a single
      patient. Acute and chronic inflammatory demyelinating polyradiculoneuropathies
      (AIDP and CIDP) produce global limb weakness. AIDP may occur at seroconversion
      and it can therefore be the initial manifestation of HIV-1 infection. CIDP
      generally occurs in the mid to late stages of HIV-1 infection. Progressive
      polyradiculopathy (PP) occurs in patients with advanced immunodeficiency and is
      generally caused by the opportunist cytomegalovirus (CMV) infection.
      Mononeuropathy multiplex (MM) in early stages of HIV-1 infection is immune
      mediated, whereas in advanced AIDS it is caused by the CMV infection. Finally,
      subclinical autonomic nervous system involvement is common in all stages of HIV-1
      infection. Because HIV-1-associated neuropathies are diverse in their etiology
      and pathogenesis, a precise clinical diagnosis is required to formulate a
      rational therapeutic intervention.

PMID- 11293808
TI  - Transformation of undifferentiated Thy-1lo B220+ thymic lymphoid cells by the
      Abelson murine leukemia virus.
AB  - Intrathymic injection of the Abelson murine leukemia virus (A-MuLV) results in
      transformation of immature T and B lymphoid cells. In this report we demonstrate
      that the concentration of A-MuLV injected into murine thymi influences the
      selection of the transformation target. Thus, concentrated A-MuLV gives rise to
      Thy-1+ B220- thymomas. In contrast, dilute virus induces B220+ thymomas that also
      express low levels of Thy-1 (Thy-1lo), a phenotype that is similar to marrow
      derived progenitor B-lymphoid cells (pro-B cells) that are highly susceptible to
      A-MuLV transformation in vitro. However, rare B220+ lymphoid cells isolated from
      normal adult thymi were not transformed by A-MuLV in vitro, while B220+ cells
      isolated from bone marrow were highly susceptible to transformation by A-MuLV.
      The Thy-1lo B220+ population in the primary thymomas had not rearranged TCRgamma,
      TCRbeta, or Igkappa genes, but contained subpopulations that assembled Ig DJ(H)
      or VDJ(H) genes and were therefore similar to transformed pro- and pre-B cells
      obtained from A-MuLV infected fetal liver and adult bone marrow, respectively.
      However, unlike A-MuLV-transformed pro- and pre-B cells, many (40-70%) of the Thy
      1lo B220+ transformed thymoma cells had not rearranged Igh genes, and therefore
      appear to represent undifferentiated lymphoid cells. We conclude that A-MuLV may
      transform an undifferentiated lymphoid target in the thymus.

PMID- 11293809
TI  - Expression of T-cell receptor beta-chain mRNA and protein in gamma/delta T-cells
      from euthymic and athymic rats: implications for T-cell lineage divergence.
AB  - The relationship between alpha/beta and gamma/delta T-cell lineages was studied
      in rats using RT-PCR analysis of TCRbeta transcripts in gamma/delta T-cell
      hybridomas and an intracellular staining technique to detect TCRbeta protein in
      primary gamma/delta T-cells. We report the presence of functional TCRbeta
      transcripts in 2/9 gamma/delta T-cell hybridomas. About 15% of peripheral
      gamma/delta T-cells and thymocytes also express TCRbeta protein, giving a minimum
      estimate for successful Tcrb rearrangement based on ex vivo single cell analysis.
      In athymic rats, gamma/delta T-cells expressing intracellular beta protein are
      present but at a lower frequency than in euthymic controls, suggesting that in
      the thymus, more gamma/delta T-cell precursors pass through a stage where
      functional beta rearrangement has occurred than in extrathymic sites. Analysis of
      TCR expression in purified transitory immature CD4-8+ (iCD8SP) thymocytes and
      their spontaneously developing CD4+8+ (DP) progeny showed that TCRy mRNA is
      expressed in iCD8SP cells but not in their immediate DP progeny that reinitiate
      RAG-I transcription and commence alpha/betaTCR expression. We conclude that rat
      gamma/delta T cells can separate from the alpha/beta lineage after TCRbeta
      expression, but not after entry into the DP compartment.

PMID- 11293810
TI  - In vivo detection of intracellular signaling pathways in developing thymocytes.
AB  - Information regarding the intracellular signaling processes that occur during the
      development of T cells has largely been obtained with the use of transgenic mouse
      models, which although providing invaluable information are time consuming and
      costly. To this end, we have developed a novel system that facilitates the in
      vivo analysis of signal transduction pathways during T-lymphocyte development.
      This approach uses reporter-plasmids for the detection of intracellular signals
      mediated by the mitogen-activated protein kinase or cyclic AMP-dependent protein
      kinase. Reporter-plasmids are transfected into thymocytes in fetal thymic organ
      culture by accelerated DNA/particle bombardment (gene gun), and the activation of
      a signaling pathway is determined in the form of a standard luciferase assay.
      Importantly, this powerful technique preserves the structural integrity of the
      thymus, and will provide an invaluable tool to study how thymocytes respond to
      normal environmental stimuli encountered during differentiation within the thymic
      milieu. Thus, this method allows for the monitoring of signals that occur in a
      biological time frame, such as during differentiation, and within the natural
      environment of differentiating cells.

PMID- 11293811
TI  - Maturation of lymphocyte immunophenotypes and memory T helper cell
      differentiation during development in mice.
AB  - The goal of this study was to systematically investigate the ontogeny of lymphoid
      populations throughout postnatal development. In CD-1 mice, peak lymphocyte
      numbers occurred in blood on postnatal day 10 (d10) including those for natural
      killers (NK1.1), B cells (CD19), T helper (CD3CD4), naive T helper
      (CD4CD62LposCD44low), memory T helper (CD4CD62LnegCD44high), and T cytotoxic
      (CD3CD8) cells. As percent of total lymphocytes, peaks were achieved by d10 for
      all T helper subtypes but not B cells which declined to a nadir. In spleen,
      lymphocyte numbers increased exponentially after d10. Proportionately, NK and T
      cells peaked on d10, declined by d20, and increased 2-3-fold by d45. Naive T
      cells constituted the majority of lymphocytes during development while memory
      cells gained to 2.2% (blood) and 12% (spleen) by d20. C57BL/6 mice had similar
      profiles except that the B cell nadir and T cell subset peaks were at d5.
      Peripheralization of critical numbers of lymphocytes by d10, and importantly,
      development of a repertoire of memory cells by d20, may define immune response
      capabilities that close the period of immaturity for the neonate.

PMID- 11293812
TI  - Increased thymic B cells but maintenance of thymic structure, T cell
      differentiation and negative selection in lymphotoxin-alpha and TNF gene-targeted
      mice.
AB  - TNF, lymphotoxin (LT) and their receptors are expressed constitutively in the
      thymus. It remains unclear whether these cytokines play a role in normal thymic
      structure or function. We have investigated thymocyte differentiation, selection
      and thymic organogenesis in gene targeted mice lacking LTalpha, TNF, or both
      (TNF/LTalpha-/-). The thymus was normal in TNF/LTalpha-/- mice with regard to
      cell yields and stromal architecture. Detailed analysis of alphabeta and
      gammadelta T cell-lineage thymocyte subsets revealed no abnormalities, implying
      that neither TNF nor LT play an essential role in T cell differentiation or
      positive selection. The number and distribution of thymic CD11c+ dendritic cells
      was also normal in the absence of both TNF and LTalpha. A three-fold increase in
      B cell numbers was observed consistently in the TNF/LTalpha-/- thymus. This
      phenotype was due entirely to the LTalpha deficiency and associated with changes
      in the hemopoietic compartment, rather than the thymic stromal compartment of
      LTalpha-/- mice. Finally, specific Vbeta8+ T cell deletion within the thymus
      following intrathymic injection of staphylococcal enterotoxin B (SEB) was TNF/LT
      independent. Thus, despite the presence of these cytokines and their receptors in
      the normal thymus, there appears no essential role for either TNF or LT in
      development of organ structure or for those processes associated with T cell
      repertoire selection.

PMID- 11293813
TI  - Kinetics of tumorigenic vascular endothelial growth factor signalling and its
      significance in human hepatocellular carcinoma cells.
AB  - Ras-VEGF-concerned angiogenesis is correlated with oncogene maintenance,
      tumorigenesis, metastasis and resistance to anti-cancer therapies; however, this
      association is not clearly elucidated by serum VEGF, due to VEGF signalling in
      blood cells themselves. The present study aimed to elucidate tumorigenic VEGF
      signalling in eight human HCC cell types and reveal the kinetics of tumorigenic
      VEGF signalling in three time intervals, thereby discovering the relationships of
      VEGF-concerned angiogenesis signalling with the extent of the human HCC cell
      growth, metastasis and resistance to anti-cancer drugs, by using the poorly
      metastatic SMMC7721, 7402/D+ (doxorubicin-resistance) and 7402/D- (doxorubicin
      withdrawal), the highly metastatic MHCC1 non-transfected human HCC cell lines,
      and the highly metastatic A3-1, F8, F11 and E3 human HCC cell lines transfected
      with expressing green fluorescence protein into the phenotype of MHCC1 cells, and
      quantitative 'sandwich' ELISA analyses. The unique results indicated attributes
      and objective laws as follows. Human HCC cell growth requires time-dependent
      tumorigenic VEGF signalling; levels of VEGF signalling are positively correlated
      with each cell phenotype itself; and levels of VEGF signalling are inversely
      correlated with the possibility of metastasis and drug resistance. The contrast
      data first reveal important clues for exploring dual metastatic mechanisms via
      tumor cell-generated non-endothelium vasculogenesis and VEGF-endothelium-attached
      angiogenesis that may be essential for developing novel strategies aimed at VEGF
      concerned signal networks in ischemic/metastatic diseases and transgenic models.

PMID- 11293814
TI  - The serum levels of IL-12 and IL-16 in cancer patients. Relation to the tumour
      stage and previous therapy.
AB  - In this study the serum levels of the cytokines IL-12 (p40 and p70) and IL-16,
      and the number of cells which produce them (monocytes, CD8+ T cells, B cells),
      were measured in 76 cancer patients with different types of cancer (breast >
      gastrointestinal > uterine/ovarian > renal/bladder) and compared with 28 healthy
      controls. The patients were divided into four groups: stage I+II without or after
      chemo/radiotherapy, and stage III+IV without or after chemo/radiotherapy. The
      distribution of patients in the groups was similar. The levels of cytokines were
      determined by ELISA, the number of the immunocompetent cells by flow cytometry.
      The serum values of IL-12 were significantly elevated in each tumour stage both
      without and after additional chemo/radiotherapy. They correlated positively with
      the progression (P < 0.02). The serum values of IL-16 were only significantly
      increased in tumour stage III+IV without or after chemo/radiotherapy. The number
      of monocytes showed no alteration in any investigated group, chemo/radiotherapy
      significantly reduced the number of CD8+ T cells at each stage, and the number of
      B cells was negatively correlated with the disease progression (P < 0.03). The
      results indicate that there is an increase of IL-12 and IL-16 in sera during
      tumour progression due only to an alteration in the function of the
      immunocompetent cells, not to an increased number. This investigation reports for
      the first time that IL-16 is involved in cancer diseases.

PMID- 11293815
TI  - Laser biostimulation of cartilage: in vitro evaluation.
AB  - An in vitro study was performed to evaluate the laser biostimulation effect on
      cartilage using a new gallium-aluminium-arsenic diode laser. Chondrocyte cultures
      were derived from rabbit and human cartilage. These cells were exposed to laser
      treatment for 5 days, using the following parameters: 300 joules, 1 watt, 100
      (treatment A) or 300 (treatment B) hertz, pulsating emission for 10 minutes,
      under a sterile laminar flow. Control cultures (no treatment) received the same
      treatment with the laser device off. Cell viability was measured by MTT assay at
      the end of the laser treatment and then after 5 days. Neither rabbit nor human
      cultured chondrocytes showed any damage under a light microscope and
      immunostaining control following laser treatment. The MTT test results indicated
      a positive biostimulation effect on cell proliferation with respect to the
      control group. The increase in viability of irradiated chondrocytes was
      maintained for five days following the end of the laser treatment. The results
      obtained with the Ga-Al-As diode laser using the above tested parameters for in
      vitro biostimulation of cartilage tissues provide a basis for a rational approach
      to the experimental and clinical use of this device.

PMID- 11293816
TI  - Hematopoietic stem cells: old and new.

PMID- 11293817
TI  - Regulation by phagic T-lymphocytes of a (pluripotent?) organ stem cell present in
      adult human blood. A beneficial exception to self-tolerance.
AB  - Stem cells isolated from adult human blood are able to give rise to several
      different kinds of cell types such as mesenchymal cells, including striated
      muscle cells, hepatocytes, and endothelial-cells. Because independently studied
      by authors whose interests focused on particular tissue types, these stem cells
      have been described as different. However, they might well represent one unique
      population of pluripotent stem cells in homeostatic equilibrium with the
      'reserve' stem cells buried in organs. In the blood, these stem cells have a
      monocytic phenotype. In in vitro culture, once they have adhered, they
      spontaneously differentiate into diverse types of cells reminiscent of embryonic
      stem cells in culture. Normally, they are almost quiescent cells. But under
      precise circumstances such as wound-healing, they may proliferate and migrate to
      the right organ to give rise there to the right type of cells, in order to
      participate in the repair process. Indeed, such a powerful stem cell needs to be
      tightly controlled. We illustrate here, by time-lapse videocinematography, how a
      special subpopulation of T-lymphocytes, for which we coined the name 'phagic T
      lymphocytes' (PTLs), destroys these stem cells as soon as they differentiate in
      vitro, i.e., without the purpose of a repair. These stem cells express
      constitutively HLA-DR molecules and therefore can act as antigen-presenting cells
      able to activate phagic T-lymphocytes. The targets of these activated phagic T
      lymphocytes are the differentiated stem cell themselves. Phagic T-lymphocytes are
      attracted by the stem cells, circulate around them, then penetrate and circulate
      inside them until the latter 'explode'. This mechanism of destruction by phagic T
      lymphocytes is unique and seems to be normally restricted to stem cells. It
      represents a beneficial exception in self-tolerance since it avoids the
      accumulation of these stem cells out of healing purposes. Interestingly, in
      disorders such as fibrosis and/or some malignant proliferations, these stem cells
      proliferate, escape destruction by phagic T-lymphocytes and, as a consequence,
      accumulate, giving rise to a 'tissue' when cultured in vitro.

PMID- 11293818
TI  - Human neural stem cells in vitro. A focus on their isolation and perpetuation.
AB  - Because of their ability to generate all the cell types in the nervous system,
      neural stem cells are promising candidates for the development of cellular and
      genetic therapies for nervous system disorders and, in particular,
      neurodegenerative diseases. In recent years, researchers have discovered ways of
      expanding and perpetuating these cells in culture, as well as different sources
      for these tissue-specific stem cells, ranging from embryonic to adult tissue, and
      also from human pluripotent stem cells. Current efforts are oriented to the
      understanding of the molecular mechanisms controlling their fate decisions, their
      genetic engineering, and how to harness their potential to make them useful from
      a therapeutic point of view.

PMID- 11293819
TI  - Intracellular cytokine profile of CD14 positive cells in patients with
      hematologic malignancies and solid tumors during hematologic recovery phase after
      intensive chemotherapy designed to mobilize peripheral blood stem cells.
AB  - We studied intracellular cytokines in monocytes by flow cytometry from 28
      patients with hematologic malignancies and solid tumors to analyze the role of
      monokines in the hematologic recovery phase for peripheral blood stem cell
      harvest. The patients were divided into three groups: the first group, A, had a
      documented infection; the second group, B, had fever of unknown origin; and the
      third group, C, was afebrile. We found an increase in intracellular IL-1alpha, IL
      6, IL-8 and TNF-alpha positive monocytes as CD14 positive gated cells cultured
      with lipopolysaccharide in all groups, but no increase was found with medium only
      when cultured for 4 h. We also found an increase in intracellular IL-1a, IL-6, IL
      8 and TNF-alpha positive monocytes cultured with autologous serum for 4 h, but
      only in group A. The rate of intracellular cytokine positive cells was higher in
      monocytes cultured with only autologous serum from group A patients compared to
      those cells from the other groups; the data concerning IL-1a, IL-6 and TNF-alpha
      reached statistical significance (P < 0.05). However, increasing intracellular
      cytokine levels in the control group of patients exhibiting only infectious
      disease were observed. Thus, it appear that pro-inflammatory intracellular
      cytokine levels in monocytes are only related to microbial infections.

PMID- 11293820
TI  - The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular
      fluids.
AB  - A variant of the normal extracellular cysteine protease inhibitor cystatin C
      (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid
      angiopathy (HCCAA). It has been suggested that the mutation causes cellular
      entrapment of L68Q-cystatin C in vivo and that the variant protein is not
      secreted to extracellular fluids. In order to test this hypothesis, we used
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry in
      an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in
      plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five
      investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The
      presence of approximately equal amounts of cystatin C dimers and monomers was
      demonstrated in plasma from HCCAA-patients, whereas only monomers could be found
      in normal plasma. L68Q-wildtype-cystatin C heterodimers seem to be present in the
      dimeric cystatin C population. CSF from six HCCAA-patients also contained
      cystatin C-dimers and monomers, but the dimeric fraction was minute. CSF from
      control patients did not contain dimeric cystatin C. These results suggest that
      the milieu of L68Q-cystatin C is important for its stability and dimerization
      status and that certain milieus might hinder its further development into
      oligomers, amyloid fibrils and other precipitating aggregates.

PMID- 11293821
TI  - Immunohistochemical investigation of the brain of aged dogs. I. Detection of
      neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage
      product, in senile plaques.
AB  - In the aging dog brain lesions develop spontaneously. They share some
      morphological characteristics with those of Alzheimer 's disease in man. Diffuse
      and primitive plaques are well known, whereas neuritic plaques rarely develop.
      Neurofibrillary tangles have not been seen in the canine. The aim of the present
      investigation was to study major age-related changes of the dog's brain using
      paraffin sections with respect to cross-immunoreactivity of tau, A beta protein
      and other immunoreactive components including hydroxynonenal protein, which is a
      marker for oxidative damage. The occurrence of neurofibrillary tangles and of the
      protein tau therein was studied in serial brain sections of two dogs with the
      Gallyas stain and by immunohistochemistry with three different antibodies against
      tau. Senile plaques were stained with a monoclonal anti-A beta (residues 8-17),
      polyclonal anti-apolipoprotein E and a monoclonal antibody against 4
      hydroxynonenal (HNE). Amyloid deposits and controls were screened by Congo red
      staining viewed in fluorescent light, followed by polarized light for green
      birefringence. With the Gallyas stain and one of the antisera against tau,
      neurofibrillary tangles were revealed in a similar dispersed pattern, whereas the
      other antitau antisera gave negative results. With the anti-HNE a positive
      reaction was found in cerebral amyloid deposits and in vascular wall areas where
      amyloid deposition was confirmed by Congo-red staining, and in perivascular cells
      and in some neurons. These results indicate that the canine with his tangles and
      plaques which show oxidative changes, forms a spontaneous modelfor understanding
      the early changes and their interrelationships in Alzheimer's disease.

PMID- 11293823
TI  - Extension of A beta2M amyloid fibrils with recombinant human beta2-microglobulin.
AB  - In order to elucidate the pathogenesis of A beta2M amyloidosis, we established an
      experimental system to study the mechanism of amyloid fibril formation or
      degradation in vitro. We compared the kinetics of A beta2M amyloid fibril (fA
      beta2M) extension with native beta2microglobulin (n-beta2M) purified from the
      urine of a patient suffering from renal insufficiency, with that with recombinant
      beta2M (r-beta2M) in vitro. n-Beta2M and r-beta2M were incubated with fA beta2M
      purified from synovial tissues excised from A beta2M amyloidosis patients. The fA
      beta2M extension reaction could be explained by a first-order kinetic model in
      both beta2Ms. The extension reaction was greatly dependent on the pH of the
      reaction mixture and maximum around pH 2.5-3.0 in both beta2Ms. The fA beta2M
      extended with both beta2Ms assumed the similar helical filament structure,
      although the fibrils extended with r-beta2M were slightly wider than those
      extended with n-beta2M and the former fibrils assumed a helical structure more
      clearly as compared to the latter. In order to obtain pure, unmodified fA beta2M,
      we next extended fA beta2M repeatedly by the algorithmic protocol with r-beta2M.
      As the generation of the extended fibrils proceeded, the initial rate of the
      extension reaction increased The ultrastructure of fibrils was completely
      preserved throughout the repeated extension steps. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and immunoblotting revealed that fA beta2M
      extended repeatedly with r-beta2M were composed solely of r-beta2M. The use of
      these r-beta2M and fA beta2M will be advantageous to assess the effects of
      several amyloid-associated molecules in the formation or degradation of fA beta2M
      in vitro.

PMID- 11293822
TI  - Micro-method to isolate and purify amyloid proteins for chemical
      characterization.
AB  - The amyloidoses represent a heterogeneous group of disorders characterized by the
      pathologic deposition as fibrils of at least 20 different precursor molecules. To
      establish definitively the specific type of amyloid protein contained in
      fibrillar deposits, such material must be extracted, purified, and subjected to
      amino acid sequence analysis. Heretofore, the chemical identification of amyloid
      components has required gram quantities of tissue. Given the often-limited
      amounts of sample available, e.g., that derived from diagnostic needle biopsies,
      we have developed a micro-method to isolate and purify amyloid from minute tissue
      specimens. The procedure involves micro-extraction of the amyloid with subsequent
      purification by SDS-PAGE, electroblotting onto PVDF membranes, excision and
      elution of amyloid protein-related bands, and reversed phase HPLC. Chemical and
      immunologic studies of isolated amyloid components have demonstrated the purity
      achieved with this technique and have provided information on the molecular mass,
      heterogeneity, and immunoreactivity of the amyloid. Further, using this
      methodology, it has been possible to obtain sufficient material for amino acid
      sequencing and thus to establish unequivocally the chemical and molecular
      composition of the fibrillar deposits. Our microtechnique has clinical import and
      also is applicable to analyses of the amyloid found in experimental small animal
      models of these disorders.

PMID- 11293824
TI  - Identical amyloid precursor proteins in two breeds of chickens which differ in
      susceptibility to develop amyloid arthropathy.
AB  - Chickens (Gallus gallus domesticus) can suffer from AA amyloidosis featuring the
      joints as major targets of amyloid accumulation. Analysis of post-mortem
      recordings from commercial chickens revealed that amyloid arthropathy frequently
      occurred in brown layer chickens, but never in white layers. The suspected higher
      susceptibility of brown layers was confirmed experimentally by inducing
      amyloidosis with an arthropathic and amyloidogenic strain of E. faecalis.
      Sequence analysis of cDNA coding for SAA, the amyloid precursor protein, revealed
      that the SAA proteins are identical in both breeds, although some nucleotide
      differences existed in the untranslated regions of the mRNAs. The chicken SAA
      gene was found to be a single copy gene which comprises 4 exons. The first of
      these exons apparently occupies a conserved position and is not translated.
      Investigation of the affected joints using in situ hybridization demonstrated
      local SAA gene expression. It is concluded that the likelihood of an E. faecalis
      induced arthritis to progress to amyloidosis is breed-dependent, but is not a
      consequence of a more amyloidogenic SAA.

PMID- 11293825
TI  - Early liver transplantation is essential for familial amyloidotic polyneuropathy
      patients' quality of life.
AB  - Nineteen patients, who had undergone liver transplantation for familial
      amyloidotic polyneuropathy, had answered a quality of life questionnaire
      including 61 questions on somatic and mental symptoms, social aspects of life,
      confidence and satisfaction before, one year, and two years after
      transplantation. We found that patient satisfaction was generally good two years
      or more after the transplantation. Most of the patients were very or quite
      satisfied with the result. All of them had the drive to go on and felt hopeful
      about the future. However, on the second follow-up, 37% of the patients noted
      that they felt more insecure in their everyday life and there was a significant
      difference between the two assessments. The diarrhea score became worse between
      one and two years after the transplantation and was closely related to the
      duration of the gastrointestinal symptoms and to the duration of the disease
      before transplantation. The mental symptoms also increased significantly between
      the evaluations and this related to the severity of the somatic symptoms. Our
      conclusion is that liver transplantation should be performed before advanced
      somatic symptoms start to develop in order to improve the patients' chances of a
      good quality of life following liver transplantation.

PMID- 11293826
TI  - Abdominal CT findings in nephropathic amyloidosis of familial Mediterranean
      fever.
AB  - To evaluate the abdominal CT features of reactive amyloidosis, abdominal CT scans
      of 20 patients with amyloidosis of familial Mediterranean fever (FMF) were
      reviewed and compared with abdominal CT scans of 2 control groups: 22 patients
      with chronic renal failure (CRF) due to non-amyloidotic kidney diseases and 40
      patients with normal kidney function. The kidney size of patients with
      amyloidosis of FMF were found to vary during the course of the disease from
      normal or slightly larger than normal at the proteinuric phase, to smaller than
      normal and comparable to kidney size in CRF, at the uremic stage. Compared to
      kidney disease of other causes, more patients with FMF-amyloidosis had dense
      kidneys with coarse parenchymal calcification and calcification in other
      abdominal organs. Patients with FMF-amyloidosis had fewer aortic calcifications
      than patients with non-amyloidotic kidney disease. These findings suggest that
      kidney disease of reactive amyloidosis may have abdominal CT findings
      distinguishing it from other types of kidney diseases.

PMID- 11293827
TI  - Symptomatic destructive spondyloarthropathy secondary to beta2-microglobulin
      amyloidosis. Report of four cases.

PMID- 11293828
TI  - [Earthquakes in El Salvador].
AB  - The Pan American Health Organization (PAHO) has 25 years of experience dealing
      with major natural disasters. This piece provides a preliminary review of the
      events taking place in the weeks following the major earthquakes in El Salvador
      on 13 January and 13 February 2001. It also describes the lessons that have been
      learned over the last 25 years and the impact that the El Salvador earthquakes
      and other disasters have had on the health of the affected populations. Topics
      covered include mass-casualties management, communicable diseases, water supply,
      managing donations and international assistance, damages to the health-facilities
      infrastructure, mental health, and PAHO's role in disasters.

PMID- 11293829
TI  - Use and abuse of amphetamine-type stimulants in the United States of America.

PMID- 11293830
TI  - The dilemma of diabetes: health care crisis in the Caribbean.

PMID- 11293831
TI  - Management of diabetes mellitus in three settings in Jamaica.
AB  - OBJECTIVES: To evaluate the quality of diabetic care in three clinics (one of
      them private and the other two public) in Jamaica, which is a middle-income
      country with a high prevalence (13%) of diabetes. METHODS: During a six-week
      census in 1995 at the three clinics we collected data retrospectively on a total
      of 437 diabetic patients. One of the clinics was a specialist public-hospital
      clinic ("SPMC"), one was a private group general practice ("PRMC"), and one was a
      public polyclinic ("PUBMC"). The patients' median age ranged from 56 years at
      SPMC and PRMC to 63 years at PUBMC. Median follow-up had been 6.0 years at SPMC,
      9.2 years at PRMC, and 6.3 years at PUBMC. RESULTS: Fewer than 10% of the
      patients were controlled with diet alone. Insulin was the most commonly
      prescribed agent at SPMC (46%), compared to 7% each at the two other clinics.
      Sulfonylurea drugs alone or in combination with metformin were the most common
      agents at PUBMC and PRMC. Overall, 40% of the patients had satisfactory blood
      glucose control (< 8 mmol/L fasting or < 10 mmol/L postprandial). There was no
      significant difference among the clinics in the proportion of patients with
      satisfactory blood glucose control (P = 0.26). A blood glucose measurement had
      been recorded in the preceding year in 84% of the patients at SPMC, 79% at PRMC,
      and 67% at PUBMC. Glycosylated hemoglobin was infrequently measured: 16% at SPMC,
      10% at PRMC, and 0% at PUBMC. Overall, 96% of patients had had surveillance for
      hypertension, and 81% had had surveillance for proteinuria. Surveillance for foot
      and retinal complications was generally infrequent and had been noted in
      patients' clinic records most commonly at SPMC (14% for foot complications, and
      13% for retinal complications). The staff at the three clinics seldom advised the
      diabetic patients on diet, exercise, and other nonpharmacological measures,
      according to the clinics' records. CONCLUSIONS: The management of diabetes in
      Jamaica fell short of international guidelines. Our results also indicate the
      need to better sensitize health care professionals to these standards in order to
      reduce the burden of diabetes.

PMID- 11293832
TI  - [Prevalence of migraine among primary- and secondary-school students in Merida,
      Venezuela].
AB  - OBJECTIVE: The epidemiological impact of headaches in populations is not
      adequately known since most of the data come from clinical studies. Therefore, we
      decided to survey a population of students in the municipality of Libertador, in
      the state of Merida, Venezuela, to determine the prevalence of migraines, the
      incapacitating effect of headaches in general, and the proportion of individuals
      who self-medicate. METHODS: We first used stratified sampling to choose schools
      in the municipality, and then simple random sampling to select which classrooms
      to survey. A total of 1,714 students, ranging in age from 10 to 21 years old,
      completed a survey. RESULTS: Among the students, 84.4% of them reported having
      had headaches, and 16.8% of them reported experiencing migraines. We did not find
      a noticeable incapacitating effect of migraines in this population. Of the
      students who had had headaches, 69.2% of them did not request medical care, and
      80.3% of them reported self-medicating. CONCLUSIONS: From these results we
      conclude that migraines are very frequent among this population. Judging from the
      levels of self-medication and the lack of medical attention for headaches, we
      believe there is a shortfall in health services coverage and a deficiency in
      public information, which together lead to an underreporting of headaches.

PMID- 11293833
TI  - [Physical violence against women in Santa Fe de Bogota: prevalence and associated
      factors].
AB  - OBJECTIVE: Estimate the magnitude of the problem of violence in intimate
      relationships affecting women in Santa Fe de Bogota, Colombia, and identify the
      factors related to the risk of being battered. METHODS: The data analyzed were
      collected between September 1998 and September 1999 from interviews with 3,971
      women who had a child less than 6 months old. The women interviewed were ones
      using public health services in the Suba area of Bogota, either for pediatric
      attention (well-baby services, vaccination, an ill child) or for childbirth. Out
      of the 3,971 women, 10 of them declined to participate, and 804 of them were not
      in an intimate relationship and were excluded from the analyses. RESULTS: Of the
      3,157 participants, 26.5% of them reported that their current partner had slapped
      or pushed them, and 13.3% reported they had been hit with a fist, kicked, hit
      with some object, or beaten, or threatened with a knife or gun. In addition,
      26.2% of the women said that their partner imposed some prohibition on them (on
      social activities, work, family planning, etc.). In the bivariate analyses,
      violence was significantly associated with: less schooling and lower income (P <
      0.001), having more children (P < 0.001), a longer period of time living with the
      partner (P < 0.001), more frequent conflict with the partner (P < 0.001), not
      having other family members living in the home (P < 0.01), a history of abuse in
      the family of origin (P < 0.001), and prohibitions imposed by the partner (P <
      0.001). According to multivariate analysis, the two factors most strongly related
      with violence were frequency of conflict with the partner and prohibitions
      imposed by the partner. CONCLUSIONS: Public health services are a good place to
      identify victims of domestic violence, and early detection and intervention
      programs should be established there. Services to support and protect victims
      should be expanded and strengthened in order to provide those persons with
      guidance, legal assistance, education, and job training. Appropriate alternative
      services for aggressors also need to be developed.

PMID- 11293834
TI  - [Leprosy surveillance in low-prevalence situations].
AB  - The majority of the countries in Latin America have reduced the prevalence of
      leprosy to less than 1 case for every 10,000 persons. The next step in these
      countries is to eliminate the disease at the regional and local level, in
      "pockets" that still have rates higher than 1 per 10,000. Given the demographic
      transition, the existence of areas with high transmission levels, and the
      necessity for more sensitive indicators, there is a need to change basic
      strategies, strengthen surveillance systems, and refocus resources. It is
      important to revamp efforts through such tactics as identifying priority
      geographical areas, customizing interventions, improving indicators, and
      combining passive and active surveillance. This can be done by redesigning
      surveillance systems to integrate the clinical, laboratory, epidemiological
      research, and supply components. The results of the process should provide a
      minimum set of indicators that make it possible to monitor and evaluate the
      effectiveness and efficiency of action plans for the postelimination stage.

PMID- 11293835
TI  - A Web-based diabetes care management support system.
AB  - BACKGROUND: Because of the often asymptomatic nature of diabetes and the long
      period between sustained hyperglycemia and observable complications, appropriate
      diabetes care relies on a long-term program of secondary prevention. Yet routine
      monitoring and screening among patients with diabetes is less than optimal. To
      support the provision of routine care to patients with diabetes, the Center for
      Health Services Research, Henry Ford Health System (Detroit), developed a Web
      based Diabetes Care Management Support System (DCMSS). A nonrandomized,
      longitudinal study was conducted (January 1, 1998-October 31, 1999) with 13,325
      health maintenance organization patients with diabetes who were aligned to 190
      primary care providers practicing in 31 primary care clinics. RESULTS: Three
      DCMSS features--clinical practice guidelines, patient registries, and performance
      reports--were made available via a corporate intranet within an existing
      electronic medical record. The effect of DCMSS usage frequency was evaluated on
      the likelihood of a patient's receipt of glycated hemoglobin testing, lipid
      profile testing, and retinal examinations. Logistic regression models controlling
      for patient sociodemographic and clinical characteristics, and the testing
      history of the patient, the primary care physician, and the primary care clinic,
      were fit using generalized estimating equation methods. The more often a
      physician used DCMSS, the more likely his or her patients were to receive lipid
      profile testing (OR [odds ratio] = 1.01, 95% CI [confidence interval] = 1.01
      1.02). Compared with patients of physicians who never used the system, patients
      of physicians who initiated 12 sessions were an estimated 19% more likely (95% CI
      = 7%-33%) to receive lipid profile testing. The analyses also suggested that the
      likelihood of a patient receiving a retinal exam was associated with system usage
      (OR = 1.01, 95% CI = 1.01-1.01). No relationship was found between system use and
      glycated hemoglobin testing. CONCLUSIONS: Computerized systems of clinical
      practice guidelines, patient registries, and performance feedback may help
      improve the rate of routine testing among patients with diabetes.

PMID- 11293836
TI  - Identifying and addressing medical errors in pain mismanagement.
AB  - BACKGROUND: There is strong evidence in the pain management literature that
      undertreatment of pain is pervasive despite several approaches, including use of
      national guidelines, to completely correct the problem. Although the concept of
      medical errors has primarily been concerned with adverse events, it is not
      unreasonable that mismanagement of pain could also be classified as a medical
      error. ERRORS OF PAIN MANAGEMENT: Error types can be classified as errors in
      assessment and documentation, errors in treatment and management, and errors in
      patient education. Within each of these categories, errors may be skill-, rule-,
      and/or knowledge-based, as suggested by evidence of mismanagement in various
      aspects of the pain management process as found in the literature. An examination
      of the root causes of medical errors may be used to detect system failures. At
      least ten steps can be identified in the process of pain management in the acute
      care setting, starting with admission, and errors can potentially occur at any
      step. A redesigned system could help improve error rates by incorporating use of
      skills, rules, and knowledge for effective management. CONCLUSION: A new approach
      to the unsolved problem of pain management in acute care settings is proposed;
      this approach uses the concept of mismanagement as a medical error.

PMID- 11293837
TI  - Adapting the HCUP QIs for hospital use: the experience in New York State.
AB  - BACKGROUND: The Agency for Healthcare Research and Quality developed the
      Healthcare Cost and Utilization Project (HCUP) quality indicators (QIs) in 1994.
      The Healthcare Association of New York State (HANYS; Albany), which represents
      more than 500 nonprofit and public hospitals, long-term care facilities, and home
      health care agencies, has adapted the HCUP QIs since 1997 to produce annual
      comparative reports for its member hospitals. Specifically designed for internal
      use, the reports have been well received and have drawn interest from other
      hospital associations and state health departments. METHODS: The HCUP QIs were
      applied to the New York State hospital discharge abstract. A risk adjustment
      model was constructed for each complication measure. Measures of utilization and
      access to care were adjusted for differences in patient demographics and payer
      status by indirect standardization. Data are presented in graphic format. Each
      hospital receives its own report (in both paper copy and CD-ROM) with comparisons
      to statewide norms, regional averages, and peer group averages. Report prepared
      for hospital systems include data for each affiliated hospital. CONCLUSIONS: When
      used appropriately, the HCUP QIs provide valuable information for individual
      hospitals to assess quality of care and target potential areas for improvement.
      The HCUP QIs also give hospitals a broad perspective to look beyond their own
      institutions and develop community-based quality improvement initiatives.
      Nevertheless, given the limitations that commonly exist with administrative
      databases and the lack of standard risk adjustment systems, the HCUP QIs are best
      used for internal purposes and not for public reporting.

PMID- 11293838
TI  - Use of consumer ratings for quality improvement in behavioral health insurance
      plans.
AB  - BACKGROUND: The Consumer Assessment of Behavioral Healthcare Services (CABHS)
      survey collects consumers' reports about their health care plans and treatment.
      The use of the CABHS to identify opportunities for improvement, with specific
      attention to how organizations have used the survey information for quality
      improvement, is described. METHODS: In 1998 and 1999, data were collected from
      five groups of adult patients in commercial health plans and five groups of adult
      patients in public assistance health plans with services received through four
      organizations (one of three managed behavioral health care organizations or a
      health system). Patients who received behavioral health care services during the
      previous year were mailed the CABHS survey. Non-respondents were contacted by
      telephone to complete the survey. RESULTS: Response rates ranged from 49% to 65%
      for commercial patient groups and from 36% to 51% for public assistance patients.
      Promptly getting treatment from clinicians and aspects of care most influenced by
      health plan policies and operations, such as access to treatment and plan
      administrative services, received the least positive responses, whereas questions
      about communication received the most positive responses. In addition, questions
      about access- and plan-related aspects of quality showed the most interplan
      variability. Three of the organizations in this study focused quality improvement
      efforts on access to treatment. DISCUSSION: Surveys such as the CABHS can
      identify aspects of the plan and treatment that are improvement priorities. Use
      of these data is likely to extend beyond the behavioral health plan to consumers,
      purchasers, regulators, and policymakers, particularly because the National
      Committee for Quality Assurance is encouraging behavioral health plans to use a
      similar survey for accreditation purposes.

PMID- 11293839
TI  - The role of a nurse case manager in implementing a critical pathway for
      infrainguinal bypass surgery.
AB  - BACKGROUND: A previous study showed the effectiveness of a clinical pathway for
      infrainguinal bypass surgery in reducing postoperative length of stay (LOS) in an
      acute care setting. Most of the deviations from the pathway were due to patient
      factors (50%) and/or external disposition problems (30%), but 20% were related to
      physician or system problems that could potentially be modified. The current
      study examined those factors influencing LOS following infrainguinal bypass
      surgery and the impact of daily rounds by a nurse case manager--a vascular nurse
      specialist--on LOS and pathway deviations. METHODS: Data were collected through
      detailed chart review and prospective tracking of pathway deviations. LOS was
      compared in 58 patients on the modified pathway (with the nurse case manager) to
      69 patients on the original pathway and 67 prepathway controls. Multivariate
      analysis was used to identify factors influencing postoperative LOS and to
      compare LOS among the three groups. RESULTS: Use of a nurse case manager
      significantly reduced physician-related deviations, from the pathway from 10% to
      0% (p = .015), and reduced system-related deviations from 3% to 0%. Median
      postoperative LOS was 7 days before the pathway was begun, 6 days with the
      original pathway, and 5 days after the introduction of a vascular nurse
      specialist (p = .0001). There were no differences in rates of complications,
      rates of readmission, or mortality. CONCLUSIONS: Intervention by a nurse case
      manager facilitated implementation of a critical pathway for patients undergoing
      infrainguinal bypass surgery, especially by preventing patient deviations due to
      intrainstitutional factors.

PMID- 11293841
TI  - [Snijders-Oomen Nonverbal Intelligence Test: useful for the elderly?].
AB  - The feasibility of the SON-R 5 1/2-17, a non-verbal intelligence test for deaf
      children, was investigated in a group of older adults, with a view to the future
      use of the test in older neurological patients. In a group of 58 healthy elderly
      persons intelligence was measured with the SON, the Raven Progressive Matrices
      and a Dutch reading test. The subjects were also asked for their subjective
      judgements of the tests. The SON-R 5 1/2-17 appears to be a user-friendly test.
      The high correlations between the subtests, and between the SON and other
      measures of intelligence suggest that the SON is a valid test for measuring fluid
      intelligence in elderly persons. The existing norms are not suitable when the SON
      is used in elderly people, new norms for adults should therefore be developed.

PMID- 11293840
TI  - [Increased activity of stress-regulating systems in Alzheimer disease].
AB  - Behavioral, i.e. non-cognitive, disturbances, such as anxiety, agitation, sleep
      disturbances and depression occur in the majority of Alzheimer's disease (AD)
      patients, but their neurobiological basis is unknown. Disturbance of stress
      regulating systems, like the locus coeruleus, could play an important role. The
      locus coeruleus, the main production site of noradrenaline in the central nervous
      system, is involved in phenomena like attention, arousal and the response to the
      environment. In Alzheimer's disease, there is a marked reduction of noradrenergic
      neurons in the locus coeruleus. We studied the activity in the remaining locus
      coeruleus neurons and found an inverse relationship between the number of
      remaining neurons and the noradrenergic activity. This could indicate
      compensatory activity and loss of flexibility of this system. Clinically, the
      loss of flexibility could result in an impairment to focus attention and to
      respond to the environment. These results can be related to another stress
      related system, the hypothalamo-pituitary-adrenal-(HPA)axis. This means that
      further evaluation of both of these systems is necessary.

PMID- 11293842
TI  - [Century of dementia].

PMID- 11293843
TI  - [Even capital funding system redistributes income intergenerationally. With ABP
      the elderly bear the costs themselves compared to augmented pensions for the
      younger generations].

PMID- 11293844
TI  - [Integrated health information system based on Resident Assessment Instruments].
AB  - The paper explores the meaning of Resident Assessment Instruments. It gives a
      summary of existing RAI instruments and derived applications. It argues how all
      of these form the basis for an integrated health information system for "chain
      care" (home care, home for the elderly care, nursing home care, mental health
      care and acute care). The primary application of RAI systems is the assessment of
      client care needs, followed by an analysis of the required and administered care
      with the objective to make an optimal individual care plan. On the basis of RAI,
      however, applications have been derived for reimbursement systems, quality
      improvement programs, accreditation, benchmarking, best practice comparison and
      care eligibility systems. These applications have become possible by the
      development on the basis of the Minimum Data Set of RAI of outcome measures (item
      scores, scales and indices), case-mix classifications and quality indicators. To
      illustrate the possibilities of outcome measures of RAI we present a table and a
      figure with data of six Dutch nursing homes which shows how social engagement is
      related to ADL and cognition. We argue that RAI/MDS assessment instruments
      comprise an integrated health information system because they have consistent
      terminology, common core items, and a common conceptual basis in a clinical
      approach that emphasizes the identification of functional problems.

PMID- 11293845
TI  - [A new rigid bronchoscope with a measuring tube for pressure and capnometry].
AB  - BACKGROUND: Pulmonary gas exchange under jet ventilation is usually controlled by
      pulse-oxymetry and blood gas analysis. Capnometry is not common in clinical use.
      Rigid bronchoscopes with pressure measurements are not known. Our aim was the
      development of a rigid bronchoscope with a built-in tube for the online
      measurement of airway pressure and gas composition. METHODS: We measured the
      distribution of inspiratory pressure under jet ventilation over the length inside
      a 8 x 400 mm rigid bronchoscope in a lung model and in patients. A measuring tube
      was constructed for obtaining representative values of airway pressure and
      capnometry. Using a prototype of a new rigid bronchoscope with the built-in
      measuring tube (R. Wolf Company, Knittlingen, Germany) inspiratory pressure and
      expiratory CO2 were measured during interventional bronchoscopy. The measuring
      tube was connected to the pressure control port of the jet ventilator. We applied
      jet ventilation with frequencies of 10 to 12 pulses per minute. RESULTS: The
      inspiratory pressure reaches after 10 cm distally the instrumental port a
      significant constant plateau. Via the built-in measuring tube representative
      measurement of pressure and gas can be made there. The correlation between
      arterial CO2 (paCO2) and expiratory CO2 (petCO2) was excellent (r = 0.96). To
      maintain normocapnia in 25 patients undergoing interventional bronchoscopy, the
      jet pressure had to be adjusted to values between 0.5 and 3.5 bar (median 2.5
      bar). The responding inspiratory pressure varied from 3 to 25 mbar (median 15
      mbar). A flexible bronchoscope in the working channel raises the airway pressure
      from 18 to 23 mbar. The automatic interruption of the jet-pulses by connecting
      the measuring tube to the pressure control port of the ventilator in order to
      prevent a barotrauma was found feasible. CONCLUSIONS: Simultaneous online control
      of airway pressure and gas is possible with the new rigid bronchoscope. Pressure
      depending jet ventilators can be controlled via the measuring tube to minimise
      the risk of barotrauma.

PMID- 11293846
TI  - [Measurement of the Fowler dead space in patients with pulmonary emphysema using
      C18O2].
AB  - In patients with lung emphysema, changes in lung volumes as well as changes in
      airway resistance are well known. The change in airway resistance is caused by
      obstruction of central airways, which is supposed to reduce the respiratory dead
      space. Until now, it was not possible to measure the respiratory dead space in
      patients with lung emphysema using the method of Fowler [2], because in this
      method distinction of the three phases of an inert gas expirogram is essential.
      While this distinction is easy in healthy subjects (fig. 1; expirogram 3), the
      separation of the three phases in patients with lung emphysema is not possible
      due to gradual transition of phase II into phase III in these patients (fig. 1;
      expirogram 2). The use of C18O2 as tracer gas allows to separate phase II and
      phase III even if the patients have severe emphysema (fig. 1; expirogram 1). CO2
      labeled with the stable oxygen isotope 18O (C18O2) is completely taken up in the
      gas exchanging region of the lung, but not from the conducting airways. Therefore
      C18O2 is only expired from the dead space of the lung, but not from the alveolar
      region. Hence, C18O2 allows exact measurement of the respiratory dead space in
      patients with lung emphysema. 21 healthy nonsmoking subjects and 29 patients with
      clinical signs of lung emphysema participated in this study. There was a good
      correlation between respiratory dead space, measured by the use of Ar-gas and
      C18O2-gas in healthy subjects (fig. 2). This indicates, that the use of C18O2 is
      a valid method to measure the functional dead space. As expected, there was also
      a correlation between the airway resistance and respiratory dead space in
      patients with lung emphysema (fig. 3), but not in healty subjects. There was no
      significant difference of the mean values of the respiratory dead space between
      these two groups (223 +/- 43 ml in healthy subjects vs. 227 +/- 52 ml in
      patients), even though there were large differences in airway resistance (0.20 +/
      0.10 kPa/l/s vs. 0.49 +/- 0.27 kPa/l/s). This may be due to a loss of alveolar
      function in the area of the terminal bronchioli, which is typical for
      emphysematous patients. This entails a shift of functional dead space towards
      lung periphery and therefore causes an increase of the volume of functional dead
      space. But this enlargement may be compensated by the volume reduction, caused by
      the airway obstruction. Hence, these two oppositional mechanisms may result in
      only minimal change of dead space volume.

PMID- 11293847
TI  - [Surfactant--treatment of complete lobar atelectasis after exacerbation of
      bronchial asthma by infection].
AB  - Dysfunction of airway surfactant is suggested as an important factor contributing
      to the pathogenesis of bronchoconstriction of patients with asthma. We report the
      case of a 59-year-old female who had an infect-exacerbation of her asthma
      complicated by a complete collapse of the left lower lung lobe. Only the local
      application of 150 mg of bovine surfactant resulted in a complete reexpansion of
      the lobe. Local therapy with replacement of surfactant may be a promising
      therapeutic approach in treatment of forms of atelectasis, which depend on a
      dysfunction or disturbed homeostasis of surfactant.

PMID- 11293848
TI  - [Therapeutic failure in acquired ambulatory pneumonia. Causes and differential
      diagnosis].

PMID- 11293849
TI  - [Diagnosis of idiopathic pulmonary fibrosis].

PMID- 11293850
TI  - [Pulmonary alveolar microlithiasis].
AB  - Pulmonary alveolar microlithiasis is a rare disease of unknown aetiology, in
      which calcium phosphate microliths are deposited bilaterally throughout the lung
      parenchyma. The total number of reported cases is about 400. A case of pulmonary
      alveolar microlithiasis is presented in a 50-year old man for whom the diagnosis
      was confirmed by histology via transbronchial biopsy. During a 4-year observation
      period there was no increase of the disease according to x-ray investigations and
      with respect to clinical symptoms.

PMID- 11293851
TI  - [Successful treatment of benign tracheal stenosis with a silicone stent (Polyflex
      Stent) over 5 years].
AB  - Inoperable, functional relevant stenoses of the airways can be effectively
      treated short-termed and medium-termed by means of bronchoscopic stenting
      occasionally, silicone stents cause problems after long-term periods, such as
      migration and retention of bronchial secretions. Metallic stents can lead to
      obstructing granulomas or even bronchial wall perforation. As regards long-term
      treatment with airway stents over several years, there is little experience and
      no uniform recommendations are known. We report on a 76-year old female patient
      with a severe benign subglottic tracheostenosis after tracheostomy who was
      successfully treated by means of bronchoscopic dilatation and stenting with a
      silicone stent (POLYFLEX stent). POLYFLEX Stent is a self-expanding silicone
      stent with an encapsulated monofilament network made of polyester. The network is
      completely covered by a silicone layer with a smooth inner surface (protecting
      against incrustation) and a structured outer surface of the stent (protecting
      against migration). The ends of the monofilaments were provided with a special
      protection to avoid tissue granulation and to yield x-ray contrast. During a
      follow-up of almost 5 years the stent is well tolerated and there is no
      restenosis. Complications such as migration, obstructing secretions and
      obstructing granulomas did not occur. A slight bronchial hypersecretion presented
      no problem under regular inhalation therapy with isotonic NaCl solution. 21 and
      56 months after stenting there were two episodes of minor haemoptysis. There was
      no demonstrable source of haemorrhage by bronchoscopy. After 56 months, biopsy at
      the distal opening of the stent showed a squamous cell metaplasia, but no
      granulation tissue. Microbiological analysis of bronchial secretions revealed an
      increasing, but clinically silent colonisation with potentially pathogenic
      microorganisms.

PMID- 11293852
TI  - [Solid combination of budesonide and formoterol in the treatment of bronchial
      asthma].

PMID- 11293853
TI  - [Importance of the functional magnetic resonance (fMR)in the radiological
      diagnosis].

PMID- 11293854
TI  - [MRI of the lung parenchyma].
AB  - Up to now the role of lung imaging in routine diagnostic work-up of pulmonary
      diseases has remained rather limited. However, the well-known technical problems
      of lung MRI (low spatial resolution, motion artifacts, low signal-to-noise ratio
      of the lung parenchyma) have been reduced by recent technical advances, thus
      leading to a significantly improved image quality in MRI of the lungs. Compared
      to helical CT good results have been demonstrated using a cardiac and respiratory
      triggered T2 weighted turbo spin echo sequence which should be included in every
      imaging protocol. Recent studies have proven that MRI is comparable or even
      better than the gold-standard helical CT regarding the staging of bronchogenic
      cancer and follow-up examinations of pneumonia and lung metastases. For other
      indications like the assessment of pulmonary nodules and the early diagnosis of
      pneumonia MRI has shown promising results; however these results need to be
      confirmed in larger patient groups. In patients with chronic infiltrative lung
      disease, CT scanning remains the superior imaging modality due to the inferior
      spatial resolution of MRI. In conclusion MRI is a reliable alternative imaging
      method to helical CT for many indications; in some cases it may be a promising
      additional examination method.

PMID- 11293855
TI  - Multi-slice CT urography after diuretic injection: initial results.
AB  - PURPOSE: To investigate the feasibility of CT urography (CTU) using a multi-slice
      (MS) scanner and to find out whether a low-dose diuretic injection is
      advantageous for the opacification of the urinary tract. METHODS: MS-CTU was
      performed in 21 patients with urologic diseases. In 5/21 patients, 250 ml of
      physiologic saline Solution were injected. In 16/21 patients, 10 mg of furosemide
      were injected 3-5 min before contrast material administration. A 4 x 2.5 mm
      collimation with a pitch of 1.25 and a tube current of 100-150 mA were used. Scan
      time was 12-16 sec. 3 mm thin axial images with an overlap of 67% were
      reconstructed. Multiplanar maximum intensity projection (MIP) images were
      postprocessed to obtain urographic views. Bone structures were eliminated using
      the volume-of-interest method. RESULTS: Furosemide-enhanced MS-CTU achieved
      either near complete or complete opacification in 30/32 (94%) ureters and in
      32/32 (100%) pelvicaliceal systems up to a serum creatinine of 150 mumol/l. In
      our series, only one CTU scan per patient was needed to obtain a diagnostic
      urogram after 10 min of contrast material injection. Ureteral compression was not
      necessary. When physiologic saline solution was used instead of furosemide, the
      radiopacity inside the enhanced pelvicalices was 4-5 times higher and more
      inhomogeneous. Diuretic-enhanced MS-CTU was more accurate in the depiction of
      pelvicaliceal details. In combination with furosemide, calculi were well
      identified inside the opacified urine and were safely differentiated from
      phleboliths. Postprocessing times of up to 20 minutes were problematic as were
      contrast-enhanced superimposing bowel loops on MIP images. CONCLUSION:
      Preliminary results demonstrate a good feasibility of furosemide-enhanced MS-CTU
      for obtaining detailed visualization of the entire upper urinary tract.

PMID- 11293856
TI  - [Value of digital subtraction arthrography and radionuclide arthrography in
      determination of indications and planning of revision surgery in total hip
      replacement].
AB  - PURPOSE: Clinical and radiographic findings are of little value in the diagnosis
      of hip endoprothesis loosening. Refined contrast and radionuclide arthrographic
      techniques are more precise in predicting endoprothesis loosening. Here we
      compare both techniques with respect to the surgical result. MATERIAL AND
      METHODS: 68 patients with hip pain after various arthroplasty procedure were
      investigated by clinical examination, X-ray, DSAr and AS. Surgical proof was
      obtained in 73.5%. RESULTS: An acetabular component loosening was detected in 89%
      by DSAr and in 86% by AS with a specificity for both methods of 93%. The femoral
      component loosening was seen with a sensitivity of 89% by DSAr and 100% by AS,
      respectively. Specificity of DSAr in the femoral compartment was 94%, of AS 88%.
      CONCLUSIONS: DSAr and AS are useful tools in the diagnosis of hip endoprothesis
      loosening and in planning surgical treatment. Both methods are comparable
      concerning the acetabular component, whereas AS is more sensitive in detecting
      femoral stem loosening. Combination of both methods is not recommended for
      routine diagnosis.

PMID- 11293857
TI  - [Radiological assessment of loss of disk height in acute and chronic degenerative
      lumbar disk changes].
AB  - AIM OF THE STUDY: A loss of disc height with increasing segmental mobility is an
      important reason for low back pain. The measurement of hyaluronic acid content of
      the nucleus pulposus prolaps shows a difference between acute (group 1) and
      chronic (group 2) disc degeneration. The purpose of the present investigation was
      to determine the decreasing of disc height between these two groups and the not
      symptomatic segments of these patients. METHODS: 20 human lateral preoperative X
      rays measurements according to Frobin et al. [1] were taken; group 1 with 7
      patients (mean age 41 years) and group 2 with 13 patients (mean age 44 years).
      RESULTS: There was a significant tendency (p = 0.091) to a reduction of disc
      height in group 2 between symptomatic and asymptomatic discs. CONCLUSION: The
      used method is not suitable to answer the present question conclusively.

PMID- 11293858
TI  - [Diskography findings and results of percutaneous laser disk decompression
      (PLDD)].
AB  - AIM: The aim of our study was to find a correlation between discographic findings
      and the clinical outcome of patients treated by PLDD. METHOD: At our clinic a
      total of 444 patients was treated by PLDD from 1992 until 1998. Of these, 100
      patients were included into this study by chance. All patients had discography.
      We analysed the discographic results and correlated them with the objective and
      subjective outcome after PLDD. RESULTS: Best clinical results were found in the
      group of discographic stages 7 and 8 according to Kramer. In cases of epidural
      leak of contrast medium and in cases of total degeneration, the clinical results
      were significantly poor (stages 6 and 9). CONCLUSION: In cases of ruptured
      posterior longitudinal ligament, i.e., epidural leak of contrast medium in
      discography, PLDD is not indicated. The indication for an operation first of all
      depends on the clinical symptoms but the success of the operation depends on the
      discographic findings.

PMID- 11293859
TI  - [Magnetic resonance imaging (MRI) of the bursa around the knee joint].
AB  - INTRODUCTION: Since fluid filled bursae lead to visible structures on MR images
      it is important to establish criteria to recognize them and to differentiate them
      from tumorous fluid-like structures. With this study the bursae around the knee
      joint were analyzed for potential differential diagnostic criteria such as
      localisation, size and shape. MATERIAL AND METHODS: In a retrospective study of
      133 MR exams the frequency, localization and morphology were registered. The
      frequency of occurrence was correlated with the frequency of an effusion by means
      of the chi 2 test. RESULTS: The most frequently recognized bursae were bursa
      subtendinea musculi gastrocnemii medialis (54.9%), bursa musculi semimembranosi
      (21%), and bursa infrapatellaris profunda (18.8%). 8 different bursae were
      identified in complete. Size roanged from 2 to 18 mm. The shape was round and
      ovoid. The bursa subtendinea musculi gastrocnemii medialis and bursa musculi
      semimembranosi correlated with the occureance of an effusion. CONCLUSION: Bursae
      around the knee are frequently visualized as asymptomatic fluid like structures.
      Knowledge of the typical localization, size and contour is important for
      identification and differentiation diagnosis against ganglia, cysts or joint
      recesses.

PMID- 11293860
TI  - [Variants of ossification of the stylohyoid chain].
AB  - PURPOSE: Evaluation of age-related differences in the incidence, length and
      topographic location of ossifications in the stylohyoid chain. METHOD: Panoramic
      radiographs of 380 patients (718 reviewed stylohyoid chains), subdivided into 4
      age groups (up to 20 years, 21 to 40 years, 41 to 60 years, older than 60 years),
      were reviewed and examined for the incidence, length and topographic location of
      stylohyoidal ossification. RESULTS: 221 (30.8%) of 718 reviewed stylohyoidal
      chains showed radiological variants (elongation of the stylold process and/or
      ossification of the stylohyoid ligament). With increasing age, there was an
      increase in the incidence and length of stylohyoidal ossifications (p < 0.01). A
      significant linear correlation between the length of the stylohyoidal
      ossifications and age was only found in the young age group (up to 20 years; p <
      0.01). In the young age group(up to 20 years), there was also a preferred
      presence of isolated locations in the superior stylohyoidal segment. With
      increasing age, there was a pronounced presence of ossifications in the middle
      and inferior stylohyoid segments and combinations of ossified varibilities.
      CONCLUSION: Stylohyoidal ossifications show age-related differences in incidence,
      length and topography and can also be put down to different pathological events.
      Stylohyoidal ossifications gain a different importance in adult patients from
      that in young people.

PMID- 11293861
TI  - [Perfusion MR imaging of the heart with TrueFISP].
AB  - OBJECTIVE: Development and test of a saturation-recovery TrueFISP (SR-Trufi)
      pulse sequence for myocardial perfusion MR imaging (MRI) using improved gradient
      hardware. MATERIAL AND METHODS: Measurements were performed on a 1.5 T scanner
      with prototype gradients (50 mT/m, minimum rise time 300 microseconds). T1
      weighted first-pass MRI of Gd-DTPA (0.025 mumol/kg) kinetics in the myocardium
      was performed using an SR-Trufi pulse sequence (TR/TE/alpha = 2.6 ms/1.4 ms/55
      degrees) with a saturation preparation of TD = 30 ms before the TrueFISP readout.
      Measurements were performed in volunteers (n = 4) and in a pig model of chronic
      ischemia (n = 1). RESULTS: In phantoms, the signal intensity was linear with
      contrast concentration up to 0.9 mmol/kg Gd-DTPA. MR images obtained with SR
      Trufi had a good image quality and high spatial resolution of 2.1 mm x 2.1 mm.
      Differences of the contrast agent's kinetics between a subendocardial perfusion
      deficit and neighboring myocardium were well visible on both MR images and signal
      time curves derived from the region-of-interest analysis. CONCLUSION: SR-Trufi
      appears to be an interesting new technique for the assessment of myocardial
      microcirculation using dedicated cardiovascular MR systems.

PMID- 11293862
TI  - [MRI study of left ventricular function in patients with coronary disease and
      myocardial dysfunction before and after coronary revascularization].
AB  - PURPOSE: To evaluate left ventricular (LV) myocardial function in ten patients
      with coronary artery disease (CAD) preoperatively and 6 months after coronary
      bypass grafting (CABG) by cardiac MRI. MATERIAL AND METHODS: Ten patients (mean
      65.2 +/- 5.9 years) with angiographically proven CAD and an indication for
      elective CABG underwent prospective evaluation of global LV function and regional
      wall motion by Cine-MRI at rest using a multiphase FLASH-2D sequence following
      regions of interest (ROI)-defined diagnostics of regional myocardial wall motion
      by means of levocardiography. Within the ROIs a total of 613 LV myocardial
      segments were analyzed preceding and following surgical revascularization.
      Results were compared with the data of 10 healthy volunteers. RESULTS:
      Preoperatively, patients showed reduced stroke volume and ejection fraction
      compared with volunteers (p < 0.01). Enddiastolic wall thickness (EDWT) and
      systolic wall thickening (SWT) were significantly lower in the patients (p <
      0.01). Based on preoperative levocardiography ROI-defined myocardial segments
      showed a significantly lower preoperative EDWT in areas with wall motion
      abnormalities (7.4 +/- 2.5 mm; p < 0.01) than in normal myocardium (9.2 +/- 2.1
      mm). Ejection fraction (p < 0.05), endsystolic wall thickness, and SWT (p < 0.01)
      improved significantly after bypass surgery. On ROI-defined analysis myocardial
      segments with impaired preoperative wall motion (n = 243) showed a significant
      increase of EDWT, ESWT and SWT (p < 0.01). CONCLUSION: In patients with CAD,
      cardiac MRI enables the non-invasive determination of postinfarctional LV
      remodeling with an increased EDWT of myocardial segments with normal regional
      wall motion and of the improvement in global and regional myocardial function
      following coronary bypass surgery.

PMID- 11293863
TI  - [Evaluation of a computer-assisted diagnosis system in breast carcinoma].
AB  - PURPOSE: Evaluation of a computerassisted diagnosis (CAD) system (R2 linage
      Checker 1.2). Comparison of the results of three readers with and without
      knowledge of the computer results. MATERIALS AND METHODS: The mammograms of 52
      patients, bilaterally in two planes each, with histologically proven carcinoma of
      the breast were included in the study. They were first scanned by the CAD machine
      and subsequently read by three readers with different degrees of experience in
      two sessions with and without knowledge of the computer results. RESULTS: Of the
      91 views of carcinomas, the readers detected 96%, 89%, and 85%, respectively.
      With CAD, the values rose to 97%, 93%, and 96%. The increase of the first
      observer was not significant. As for the 49 areas of malignant
      microcalcifications, the first reader showed a significant decrease of
      sensitivity, the other two readers showed no significant change. The sensitivity
      of CAD was 74% for masses and 86% for microcalcifications at a rate of 1.8 false
      positive markers per image. All but two tumors were correctly marked in at least
      one plane. CONCLUSIONS: Use of the CAD machine led to a significant increase of
      sensitivity in the detection of malignant masses by two of three observers. In
      the case of malignant microcalcifications, and for the most experienced observer,
      CAD did not improve the results. The most important problem is the high rate of
      false positive markers.

PMID- 11293865
TI  - [Percutaneous hydromechanical thrombectomy in acute and subacute lower limb
      ischemia].
AB  - PURPOSE: A prospective study should evaluate the primary and 2-year results of
      treating acute and subacute lower-limb ischemia with hydromechanical thrombectomy
      (HTE). MATERIALS AND METHODS: Consecutively 64 patients, 12 with viable and 52
      with threatening limb ischemia and onset of symptoms within 8 +/- 9 days, were
      treated and controlled for 24 months. An 8 F hydromechanical thrombectomy device
      (HTK), was used. It sucks and shreds the thrombi. The shredded particles are
      transported to the outside. RESULTS: In 8 patients a total, in the others a
      partial restoration of the vessel lumen up to 70-50% was achieved in a mean time
      of 34 minutes. Residual thrombi, underlying atherosclerotic vessel disease and
      occluded arteries with a small diameter made adjunctive interventions (balloon
      angioplasty, percutaneous aspiration thrombectomy, lysis) necessary. Clinical
      symptoms and the ankle-brachial index improved significantly (p < 0.01). Primary
      patency was 72%, 70%, 67%, and 65%; the limb salvage rates were 81%, 78%, 75%,
      and 73% for one, 3, 12, and 24 months respectively. Device-induced complications
      did not occur. CONCLUSIONS: The HTK allowed a rapid reduction of fresh thrombotic
      material without complications. In 78% of the cases adjunctive therapies are
      required for wall-adherent thrombi and when tibial vessels with smaller lumina
      are included. Long-term results are comparable to literature data for
      fibrinolytic or operative regimens. The advantage, however of the HTK seems to be
      the reduction of intervention time and intra-arterial dosage of fibrinolytic
      drugs.

PMID- 11293864
TI  - [Percutaneous stereotactic biopsy of non-palpable breast lesions using the
      Advanced Breast Biopsy Instrumentation (ABBI) system: critical evaluation of
      indication strategies].
AB  - PURPOSE: To compare the indications for biopsy with and without the use of the
      Breast Imaging Reporting and Data System. MATERIAL AND METHODS: Biopsies using
      the ABBI were performed in 62 patients with 64 non-palpable evident mammographic
      lesions. The initial decision for biopsy was made by non-radiologists due to
      suspicious microcalcifications (n = 53) and masses (n = 11). The indication was
      retrospectively reassessed by adopting the BI-RADS classification by three
      radiologists in consensus. The positive predictive value (PPV) of both indication
      strategies was assessed and compared. RESULTS: Biopsies adopting ABBI were
      performed without major side-effects and were diagnostic. Carcinoma was present
      in 14 lesions: nine specimens were diagnosed as DCIS and five as invasive
      carcinomas. For the 50 benign lesions histology revealed mastopathies (26/50) and
      fibroadenomas (8/50) as the most frequent diagnosis. The positive predictive
      value (PPV) for the initial indication was 22%, whereas PPV for BI-RADS based
      indications (categories 4 and 5) was 31%. CONCLUSION: ABBI enables
      stereotactically-guided procedures that result in representative and diagnostic
      biopsies. Standardized criteria like BI-RADS improve the PPV and should be a
      mandatory part of mammographic evaluation. Radiologists should remain involved in
      the decision making.

PMID- 11293866
TI  - [Treatment of peripheral arterial thromboembolic occlusions using a new
      percutaneous mechanical thrombectomy system].
AB  - PURPOSE: We report our experience with a new percutaneous thrombectomy device for
      the treatment of thromboembolic occlusions of peripheral arteries. MATERIAL AND
      METHODS: Between November 1999 and May 2000 12 patients (10 male) with
      thromboembolic occlusions of peripheral arteries were treated. 8 occlusions were
      located in the femoral and popliteal arteries, 3 in the infrapopliteal vessels
      and 1 in the brachial artery. In all cases a new 6 F-catheter with a rotational
      screw and a suction vacuum unit was used. RESULTS: The intervention was
      successful in 11 patients. 1 patient with a failed procedure had a duration of
      occlusion > 90 days. There were no complications. All patients were discharged on
      the same or the following day. CONCLUSION: Percutaneous treatment with the
      thrombectomy device is a feasible option in a small group of patients with
      thromboembolic occlusions of the peripheral arteries. Often additional treatment
      is necessary. The major indication seems to be acute thrombosis. The procedure is
      easy and safe to apply.

PMID- 11293867
TI  - [Results after placement of Memotherm stents in iliac and femoral arteries].
AB  - PURPOSE: To evaluate the effectivity, safety and midterm patency rates of iliac
      and femoral stent placement with the Memotherm stent (Bard-Angiomed, Karlsruhe).
      MATERIAL AND METHODS: In 41 patients (11 female, 30 male, mean age 63.9 years) 49
      lesions were treated with 50 stents. Mean lesion length was 4.8 cm for 5
      occlusions and 3.1 cm for 44 stenoses. Lesions were located in the common iliac
      (n = 31), the external iliac (n = 15), and the common femoral artery (n = 3).
      Patients were followed-up clinically, with ankle-brachial indices (ABI), and
      angiography. Angiographic patency rates (< or = 50% restenosis) were calculated
      using the Kaplan-Meier method, ABIs were compared before and after therapy with
      the Wilcoxon test. RESULTS: An immediate technical success was achieved in 48/49
      lesions (98%, intention-to-treat). Visibility of the stent was poor. Four stent
      placement procedures were complicated by an advancement of the stent, which could
      not be corrected. A thrombosis of one stent during deployment had to be treated
      surgically. After a mean of 10.4 months (6-24) 33 lesions were followed-up with
      angiography. The primary angiographic patency rate was determined to be 89.9%
      after 9 months. An improvement of at least one Fontaine stage was observed in
      85.4%. The mean ABI increased significantly from 0.64 to 0.84 after therapy.
      CONCLUSIONS: The patency rate of the Memotherm stent is comparable to that of
      other stent systems. The poor visibility and the advancement of the stent during
      deployment requires further modifications.

PMID- 11293868
TI  - [Analysis of artefacts by virtual endoscopy visualization of spiral CT data].
AB  - PURPOSE: Analysis of patterns and causes of artifacts found in endographic
      visualization of spiral CT data. MATERIALS AND METHODS: A straight perspex tube
      with a diameter of 20 mm was scanned in three different positions with ten scan
      protocols of varying table feed, increment, kernel, and signal to noise ratio
      (Tomoscan AVE, Philips). The resulting 30 CT datasets were visualized as a
      virtual endoscopy (VE) with ten different visualization protocols (Easy Vision
      4.2, Philips) of varying threshold, resolution, and perspective angle. 300 VE
      datasets were analyzed by two radiologists and compared with the visualization of
      a software-generated tube in order to differentiate scanning and software
      artifacts. RESULTS: Five different classes of artifacts have been identified. Two
      of them result from the scanning process and two from the specific visualization
      method. Spiral patterns and the unevenness of the tube wall vary with the
      scanning parameter. Moire-like patterns are caused by the VE software and depend
      on the visualization matrix. A high perspective angle distorts the size and form
      of the tube and makes it difficult for the observer to locate his position within
      the tube. The appearance of pseudoforamina depends on both the scanning and the
      visualization parameters. CONCLUSION: The knowledge of the patterns and potential
      causes of artifacts in endographic visualization of spiral CT scans are the basis
      for interpretation and optimization of this visualization method.

PMID- 11293869
TI  - [Use of a new tiltable angiography table for diagnostic and interventional CO2
      angiography].
AB  - A new tiltable angiographic table was tested for its applicability during carbon
      dioxide angiography in 11 patients. A change of position could be performed
      easily without delaying the procedure time and improved image quality in 8
      patients while carbon dioxide was applied as contrast agent. The new tiltable
      angio table--originally designed for surgical procedures performed within the
      angiosuite--proved to be of use also during percutaneous diagnostic procedures,
      particularly with carbon dioxide as a contrast agent.

PMID- 11293870
TI  - [Comparison of susceptibility artefacts of different radiofrequency electrodes at
      O.2 T. Influence of electrode positioning, pulse sequence and image
      reconstruction methods].
AB  - PURPOSE: Interventional MRI procedure monitoring requires small but accurate
      susceptibility artifacts of the instruments used. In this investigation,
      susceptibility artifacts of different RF-electrode designs were compared using a
      variety of pulse sequences and k-space acquisition methods. METHODS: 4 different
      18-gauge RF-electrodes (with three single electrodes made of stainless steel,
      copper, inconal, and a triple-clustered electrode configuration made of inconal)
      were placed in a 0.2 T MR-scanner perpendicular to the main magnetic field. Pulse
      sequences used included: TSE T2, FISP, true-FISP, PSIF, and a temperature
      sensitive ES-GRE sequence. In addition to the 2D Cartesian k-space trajectory
      with Fourier transformation (2DFT), projection reconstruction (PR) was used with
      the FISP, true-FISP and PSIF sequences. RESULTS: The best tip accuracy was
      achieved with the combination of inconal electrodes and TSE T2. The usefulness of
      the tested sequences was found to be: TSE T2 > PSIF > FISP/true-FISP > ES-GRE. In
      general 2DFT provided better or equal tip accuracy than PR. The apparent shaft
      width was smaller using the copper electrode compared to the inconal electrode.
      However, the "match shaped" tip artifact of the copper probe led to a higher
      error in tip accuracy. CONCLUSIONS: TSE-T2 sequences and Cartesian 2DFT
      acquisitions should be used for accurate tip positioning at 0.2 T. Further,
      artifact size of the electrode shaft prevents the use of inconal for temperature
      sensitive sequences. Copper electrodes can be used for these purposes, although
      copper is not considered to be biocompatible at present.

PMID- 11293871
TI  - [Laser-induced thermotherapy (LITT). Use of round and pointed laser applicator
      systems--initial results].
AB  - PURPOSE: To assess the advantages and disadvantages by using round and sharp
      laser application systems during laser-induced thermotherapy. METHOD: 6 in vitro
      examinations were performed and 12 patients with liver metastases of colorectal
      carcinoma were treated with laser-induced thermotherapy. All lesions were closely
      localised to the diaphragm, liver capsule and large intrahepatic vessels. Five
      patients were treated with the sharp and 7 patients with the round applicator
      system. After CT-guided insertion of the catheter system into the metastasis
      laser therapy was performed under MRI control (approx. 25 W, 20 min). RESULTS:
      Reduction of the distance between the laser applicator and rounded laser catheter
      tipp (approx. 0.5-1 cm) leads to better placement of the laser applicator in
      metastases located near the diaphragm, liver capsule and large intrahepatic
      vessels. Improved therapy results due to complete ablation of metastases were
      obtained. All patients treated with the round system had complete ablation of
      metastasis. In 3 of 5 patients treated with the sharp system, MRI control 2 days
      after therapy showed a residual tumour margin close to the diaphragm or to an
      intrahepatic vessel. DISCUSSION: Improved ablation can be obtained by closer
      placement of a round laser catheter in liver metastasis located near the
      diaphragm, liver capsule and large intrahepatic vessels.

PMID- 11293872
TI  - [Comparison of biphasic spiral CT and MnDPDP-enhanced MRI in the detection and
      characterization of liver lesions].
AB  - INTRODUCTION: To evaluate the efficacy of biphasic spiral CT and MnDPDP
      (Teslascan, Nycomed Amersham) enhanced MR imaging to detect and classify liver
      lesions. MATERIALS AND METHODS: 39 patients with known or suspected liver lesions
      were included into this study and examined with biphasic spiral CT and MnDPDP
      enhanced MRI. 25 histological reports and 1 extreme increased serum AFP value
      could be obtained from 22 patients, therefore only these 26 proven lesions were
      included into this analysis. RESULTS: From 39 patients CT revealed in 54% (14
      lesions) and MRI in 54% correct (i.e., corresponding to the histology) diagnosis.
      Correct CT/wrong MRT diagnosis and vice versa was present in only 2 lesions each.
      Differentiating into benign versus malignant lesion was successful in 73% for MRI
      and 77% for CT. In 81% MRI revealed the correct type of lesion (hepatocellular or
      non-hepatocellular) vs. 77% with CT. Sensitivity/specificity for differentiation
      into benign/malignant lesions was 86%/70% (MRI) and 87%/77% (CT) and for
      differentiation of the lesions origin 100%/80% (MRI) and 80%/75% (CT), these
      differences were not significant. MnDPDP-enhanced MRI showed significantly more
      lesions than non-enhanced MRI. CONCLUSION: MnDPDP-enhanced MRI is better than CT
      in differentiating hepatocellular liver lesions from non-hepatocellular lesions.
      After contrast enhancement with MnDPDP significantly more lesions could be
      evaluated in MRI. MnDPDP improves, in combination with biphasic helical CT, the
      diagnosis of liver lesions.

PMID- 11293873
TI  - Long-term (four years) follow-up of patients with treated nocturnal hypertension
      assessed by ambulatory blood pressure monitoring.
AB  - STUDY OBJECTIVE: Nocturnal Hypertension (NH) is an independent risk factor for
      cardiovascular morbidity and mortality (M-M). However, an inappropriate decrease
      in diastolic BP during the night significantly increases morbidity. There are no
      prospective studies on the long-term consequences on M-M in treated NH. We
      accordingly studied M-M in 107 consecutive patients with treated NH, assessed by
      ambulatory blood pressure monitoring (ABPM), during a four-year follow-up.
      PATIENTS AND METHODS: From the initial 107 patients six died (5 from brain or
      cardiovascular causes). In 65 patients it was possible to repeat the ABPM during
      the follow-up period. They were hypertensive patients class I-II (JNC IV) 62 +/-
      10 years old, 56 were male and were observed before and after starting treatment
      on a four-year follow-up period. We considered age, sex, body mass index,
      previous cerebral and cardiovascular accidents, type and number of drugs
      administered, smoking habits, plasma cholesterol, glycemia, and causal and
      ambulatory blood pressure monitoring (ABPM) (24 hr, 6 am-10 am, 10 pm-6 am and
      pulse pressure) before and after follow-up, dipper status and the period of
      follow-up. RESULTS: The patients whom died were older and had a significantly
      higher systolic blood pressure compared to the survivors. We considered two
      groups: with (A - n = 18) or without (B - n = 47) cerebral and cardiac morbidity.
      The A group had more previous cerebral and cardiovascular accidents (p = 0.05), a
      more intensive treatment (p = 0.02), and a greater fall in diastolic blood
      pressure (DBP) during the night in both absolute and percentage numbers, after
      treatment, than the B group. However, after regression analysis, the only
      independent risk marker differentiating between the two groups was the percentage
      fall in the DBP after treatment (dipper phenomenon) (p = 0.01). CONCLUSIONS: In
      65 treated hypertensive (NH) patients assessed by ABPM before and after treatment
      (four-year follow-up) we identified a group with cerebral and cardiovascular
      morbidity. These patients, in contrast with another group with no morbidity, had
      more previous cerebral and cardiovascular accidents, they were more intensively
      treated, and they had a greater fall in diastolic blood pressure after therapy
      (absolute and percentage values). However, after regression analysis the
      diastolic nocturnal blood pressure dipper phenomenon after treatment was the only
      risk marker associated with morbidity. In such cases it is possible that
      treatment guided by ABPM can decrease morbidity.

PMID- 11293874
TI  - Hemorrhagic stroke: experience of an internal medicine department.
AB  - Stroke is the third leading cause of death in most industrialised countries,
      among adults aged 65 years or more. In Portugal, however, it is the leading cause
      of death. Intracerebral hemorrhages comprise approximately 10 to 15% of all
      strokes. This particular type of stroke is associated with a worse prognosis.
      There is little published data concerning stroke in the Portuguese population,
      especially on the hemorrhagic type of the disease. The aim of the present study
      was to improve our knowledge on the epidemiology of hemorrhagic strokes in our
      community. The hospital charts of 60 patients with intracerebral hemorrhage who
      were admitted to our wards during the years of 1997 and 1998 were retrospectively
      reviewed. There was a predominance of male patients aged over 65. In most cases
      (78.3%), no causal factor was identified (spontaneous or "primary" hemorrhagic
      stroke). Hypertension was present in 80% of cases and was the most common risk
      factor. The percentage of putaminal and thalamic hemorrhages (48.3%) was similar
      to the percentage of lobar hemorrhages (46.7%). This differs from other studies.
      The prognosis of our patients was fairly good, with 38% of all cases being
      independent at thirty days. The 30-day case fatality rate was 10%. As in other
      studies, advancing age, a low Glasgow Coma Scale score, a large hemorrhage size
      and the intraventricular extension of blood were associated with a worse outcome.

PMID- 11293875
TI  - [Deciding about pacing mode in sinus node dysfunction: should carotid sinus
      massage be performed and in which circumstances?].
AB  - OBJECTIVE: To state the incidence of carotid sinus syndrome (CSS) with
      atrioventricular node manifestation in patients with sinus node dysfunction (SND)
      and indication for a definitive pacemaker (PM), we propose a new protocol between
      atrial pacing AAI and double chamber DDD. POPULATION AND METHODS: 69 patients
      (PTS) (male 71%), median age 65 +/- 10 years, with SND (normal PQ and no
      intraventricular conduction defect), that had a PM implant following the protocol
      that included carotid sinus massage for the pacing decision, were followed
      prospectively between December 1995 and November 1999. During the protocol we
      implanted DDD PM in PTS with Wenckebach less than 130 or Wenckebach equal/over
      130 and CSS. At least, in PTS with Wenckebach equal/over 130 and no CSS we
      implanted AAI PM. The follow-up was between 4 months and 4 years, with clinical
      evaluation in the first and fourth months and then half yearly, with carotid
      sinus massage in the first evaluation. RESULTS: About 1/4 of the 69 patients
      followed had SND without carotid sinus syndrome, or atrioventricular node
      repercussion; the SND involved the atrioventricular node in 56% of the patients,
      and there was a relation between the SND and carotid sinus syndrome in 18.8%. The
      follow-up revealed, in all patients, a complete remission of the symptoms, and
      when we repeated the carotid sinus massage in the first evaluation, there was a
      response like in the surgery room, in all patients. CONCLUSIONS: There is a
      significant number of patients with SND and carotid sinus syndrome. The carotid
      sinus massage performed in the surgery room does not influence the test
      sensitivity and specificity in the diagnosis of carotid sinus syndrome. The
      authors think that carotid sinus massage should be considered in the protocol
      that defines the pacing mode, in patients with SND, and that influence the choice
      of pacemaker in 18.8% of patients.

PMID- 11293877
TI  - [Changes in regional wall contractility induced by effort in women with normal
      coronary angiography --report of a clinical case].
AB  - The diagnosis of coronary artery disease in women has been thought to be more
      difficult than in men, owing to the lower overall prevalence of disease in women,
      as well as more subtle clinical presentations and unspecific changes in ST
      segment. The authors report a clinical case of a 61-year old woman, with low
      cardiovascular risk and history of atypical chest pain and a positive treadmill
      exercise test on the inferior leads. She did an exercise echocardiogram that
      revealed severe hypokinesis on the anterior wall and septum with late
      normalization. The patient was submitted to a coronary angiography that revealed
      normal arteries. An echocardiogram with hyperventilation was later performed and
      showed the same ischemic changes as exercise did, on the inferior leads but no
      regional wall motions abnormalities occurred. The patient is currently
      asymptomatic under calcium antagonist treatment.

PMID- 11293878
TI  - Transcatheter occlusion of a residual left superior vena cava causing right-to
      left shunt in a Fontan patient with a new occlusion device.
AB  - We describe the management of a residual left superior vena cava connected to the
      coronary sinus and causing right-to-left shunt at atrial level in an 8 year-old
      child, with modified Fontan operation (total cava pulmonary connection) by
      transcatheter closure with a new duct occluder device.

PMID- 11293876
TI  - [Time's paradigm in primary angioplasty].
AB  - The use of primary angioplasty in the treatment of acute myocardial infarction
      (AMI), as opposed to fibrinolysis, is well established, as long as performed by
      an experienced team. The benefits are "time-dependent", hense the rational for
      the sentence "Time is Muscle". It is very important to assess the time factor,
      mainly if the therapeutic option is primary angioplasty, since it is necessary to
      set up a full range of conditions related to this type of specific treatment
      (human, material and logistical). In the current study was analysed the in and
      out of hospital time sequence of 99 patients with AMI that underwent primary PTCA
      during the year of 1999. The main goal was to assess if the performance of this
      procedure outside regular working hours could have any significant impact on the
      "time of in-hospital ischemia". The different time durations were prospectively
      recorded according to a protocol that was previously established and filled for
      each patient by the lab team. The authors conclude that: a) the average in
      hospital time delay in the treatment of AMI by PTCA was not significantly
      influenced by the fact that the procedure was performed outside the regular
      working hours of the lab; b) the main component of the "ischemic in hospital
      time" corresponds to the time between the patient's admission and the decision
      making time for PTCA. Although the average decision making time for PTCA is too
      long and must be optimized, the average total in hospital ischemic time (99-105
      minutes) compares favorably with other previous reports in the literature.

PMID- 11293879
TI  - [Interaction between antiplatelet agents and angiotensin-converting enzyme
      inhibitors].
AB  - The use of angiotensin converting enzyme inhibitors (ACEIs), as well as of acetyl
      salicylic acid (ASA) in patients with hypertension, myocardial infarction or
      heart failure is recommended by the guidelines issued by several respected
      cardiological societies. However, some authors have argued that ASA may decrease
      the effectiveness of ACEIs by decreasing the release of prostagandins. Although
      such negative interaction is still not conclusively demonstrated, the merits of
      the use of this association should be judged in each individual patient with
      heart failure. It seems prudent to use low doses of ASA (< or = 250 mg/day) in
      these patients. ADP antagonists may constitute an alternative to ASA since they
      do not block prostaglandin synthesis.

PMID- 11293880
TI  - [Glossary of terms and concepts used in scientific evidence based cardiology.
      Part II: clinical trials].
AB  - The papers published by the Revista about Evidence-Based Cardiology (EBC) have,
      so far, discussed general aspects of the theory as well as practice of EBC, using
      simple terms and concepts. We need a detailed description of the general, as well
      as specific, concepts applicable to EBC, in order to understand better this
      methodology and to facilitate the reading. In this second article (the first--on
      general aspects--was published in the last issue of the Revista) we present a
      glossary of terms applicable to clinical trials and systematic reviews.

PMID- 11293881
TI  - [Mitral endocarditis with valvular perforation and severe mitral regurgitation].

PMID- 11293882
TI  - [Efficacy of implantable cardioverter-defibrillators for the prevention of sudden
      death in patients with hypertrophic cardiomyopathy].

PMID- 11293883
TI  - [Prevalence of cardiovascular risk factors in a rural population aged between 25
      and 44 years].

PMID- 11293884
TI  - Osteopenia in Puerto Ricans with Crohn's disease.
AB  - BACKGROUND: Osteopenia has been reported in association to Inflammatory Bowel
      Disease, and in particular Crohn's disease. The use of corticosteroids, resection
      of the ileum, malabsorption, poor calcium intake, and the effect of inflammatory
      cytokines have all been considered as contributing factors. As Crohn's disease is
      more prevalent in young people, when peak bone mass is achieved, the presence of
      osteopenia is especially significant. OBJECTIVES: The aim of this study was to
      evaluate the bone density of patients with Crohn's disease in the University of
      Puerto Rico IBD Clinic; to determine the prevalence of osteopenia in these
      patients and to correlate bone mineral density with risk factors for osteopenia.
      METHODS: Sixty-six patients, 30 males and 36 females were included. After
      informed consent, demographic, clinical and metabolic data was obtained. Serum
      albumin, calcium, inorganic phosphorus and alkaline phosphatase were measured.
      Body mass index (BMI) was calculated. Bone density was determined by DEXA of the
      lumbar spine and femur and expressed as the Z score (standard deviations from
      normal correlated with sex and age). Severe osteopenia was a Z score > or = -2
      and osteopenia was Z < or = -1.99 or > or = 1.01. Results were expressed in
      means. Pearson correlation coefficient was used for quantitative variables and
      Pearson chi-square for categorical values. RESULTS: Osteopenia was present in the
      hip in 69% and in the lumbar spine in 68%. Most patients had received steroids;
      the difference between treated and not treated patients was not significant.
      Osteopenia did not correlate with ileal resection, gender, BMI, disease
      characteristics or biochemical parameters. CONCLUSIONS: Low bone density was
      frequent in patients with Crohn's disease, but no specific risk factors could be
      identified. Bone density should be determined in patients with Crohn's disease in
      order to institute appropriate therapeutic measures.

PMID- 11293885
TI  - Mortality study in Puerto Ricans with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the most common causes of death among Puerto Ricans with
      systemic lupus erythematosus. METHODS: Chart and record review of all deaths
      related to SLE complications from 1960 to 1994 at the University of Puerto Rico
      Hospital. RESULTS: Out of 662 patients diagnosed with SLE 161 (24%) died. There
      were 151 (94%) females and 10 (6%) males. Mean duration of disease was 11.5
      years. Mean age at death was 37 years. The primary causes of death were infection
      in 44 (27%), uremia in 42 (26%), cardiovascular complications in 33 (20%),
      central nervous system complications in 18 (11%), and pulmonary complications
      (other than infectious pneumonia) in 12 (7%). CONCLUSIONS: The most common causes
      of death in SLE were infections and renal disease.

PMID- 11293886
TI  - [Prevalence of antiphospholipid syndrome in patients with systemic lupus
      erythematosus at the University Hospital of Puerto Rico].
AB  - This is a retrospective study based on a population of 80 patients with
      connective tissue diseases from the University Hospital of Puerto Rico. Among the
      population, 62 (77.5%) of the patients had Systemic Lupus Erythematosus (SLE),
      whom we were most interested to monitor. The investigation revealed an incidence
      of 13.8% of anthiophospholipid syndrone within the general population. Among the
      patients with SLE it was 12.9%, and only 5.5% among the population with other
      diagnoses. The antibody found with the highest frequency within the systemic
      lupus erythematosus population was the anticardiolipin IgG (30.6%) and lupus
      anticoagulant (17.7%). The antibody frequency among patients with other diagnoses
      was only 5.5% for lupus anticoagulant and 5.5% for anticardiolipin IgM (the only
      one found). Among SLE's clinical manifestations, the most frequently found were
      thrombocitopenia and pregnancy complications.

PMID- 11293887
TI  - Effect of flumazenil on electroencephalographic patterns induced by midazolam.
AB  - BACKGROUND: Flumazenil is a competitive benzodiazepine receptor antagonist,
      reverts the sedation effects of benzodiazepines and its effect on
      electroencephalographic (EEG) patterns is controversial. The purpose of this
      study was to describe flumazenil's effect on EEG patterns of patients undergoing
      conscious sedation. METHODS: Ten voluntary patients, aged 16-23, at elective oral
      surgery had conscious sedation with midazolam and local anesthesia. After the
      procedure, sedation was reversed with flumazenil. Each patient had 4 EEGs of 4
      minutes each: baseline, 5 minutes after midazolam, prior to flumazenil, and 8
      minutes after flumazenil. A clinical neurophysiologist interpreted EEGs blinded
      to time. RESULTS: Eight patients had an awake and 2 had an awake and drowsy
      normal EEG. After midazolam all developed a diffuse beta wave and alpha wave
      attenuation or dropout. Prior to flumazenil 7 presented diffuse beta and
      scattered theta waves, and 3 an awake pattern (procedure required > 30 minutes).
      After flumazenil, reversal of beta and theta waves and appearance of alpha waves
      was noted; no changes occurred when procedure lasted more than 30 minutes. One
      patient presented with diffuse theta waves, 6 Hz. CONCLUSIONS: Flumazenil reverts
      midazolam EEG changes if administered < 30 minutes after midazolam
      administration, midazolam-induced EEG changes revert spontaneously after 30
      minutes, and flumazenil may precipitate theta activity.

PMID- 11293888
TI  - [Health in Puerto Rico in the 20th century].
AB  - The evolution in physical condition, life expectancy at birth, and access to
      preventive and curative services rapidly improved the quality of life of Puerto
      Ricans in the twentieth century. The population quadrupled to almost 4 million
      inhabitants and the crude mortality rate fell from 38 per thousand in 1900 to 7.7
      per thousand in 1997, with its most dramatic change (18.6 to 6.7) occurring from
      1941 to 1960. The great promoters of health were the general increase in
      socioeconomic level, improvements in infrastructure, and vaccines; its great
      scourges were infectious diseases (from hookworm to AIDS) and social
      dislocations, such as the war of 1917 (accompanied by epidemics and hunger) or
      the present war between illicit drug distributors. This article summarizes the
      events in the century related to health and its political and economic contexts,
      the developments in public health structures and health care, professional
      education, volunteer organizations, campaigns against infectious diseases,
      chronic causes of mortality, and environmental problems. Bringing the capacity to
      defend public health to the level of sophistication available for clinical care
      is one of the vital challenges of the twenty-first century for Puerto Rico.

PMID- 11293889
TI  - Youth violence: understanding and prevention. Part I.
AB  - Violence is a major threat to the welfare and prosperity of any society and is a
      particular area of concern how violence-related events are increasing among
      children and adolescents. A review of the most relevant literature was done to
      identify factors that are considered of risk. We found factors that are beyond
      our control. But we can work together to eliminate some conditions that promote
      violence taking in consideration children upbringing patterns, culture and
      immediate surrounding. These factors include exposure to violence-related events;
      easy access to handguns; drugs and alcohol use, untreated mental illnesses and
      incapacity/limited coping skills for conflict resolution. Prevention and
      strategies of interactions to reduce youth violence need to be based in the
      understanding and early recognition of these factors.

PMID- 11293890
TI  - The management of labor and delivery and its implications for breastfeeding.
AB  - The main professional organizations of obstetrical and pediatric care providers
      in the United States and Puerto Rico have issued official position papers in
      favor of breastfeeding. Routine labor and delivery practices, however, constitute
      frequent barriers for the initiation, type and duration of breastfeeding. Many of
      these practices, moreover, lack the scientific basis to justify their routine
      use. We analyze in this article some of the most common obstetrical practices and
      their impact on breastfeeding.

PMID- 11293891
TI  - Integrative medicine: a paradigm shift in medical education and practice.
AB  - The use of alternative/complementary medicine has been increasing considerably.
      Conventional medicine must begin to address issues related to the use, safety,
      regulation, research and education of alternative/complementary medicine.
      Integrative medicine combines conventional medicine and alternative complementary
      practices. Integrative medicine is an innovative approach to medicine and medical
      education. It involves the understanding of the interaction of the mind, body and
      spirit and how to interpret this relationship in the dynamics of health and
      disease. Integrative medicine shifts the orientation of the medical practice from
      disease based approach to a healing based approach. It does not reject
      conventional medicine nor uncritically accepts unconventional practices.
      Integrative medicine is an effective, more fulfilling human approach to medicine
      based on the benefit of the patient by following good medicine practices in a
      scientific manner.

PMID- 11293892
TI  - Can biomedical researchers benefit from political science methodologists?
AB  - The purpose of this monograph is to introduce the work of a group of political
      science methodologists, who created a series of models for estimation and
      prediction. It refers to the work of Gary King and his collaborators at Harvard
      University's Department of Government. They developed a set of computer-intensive
      simulation techniques, along with the corresponding public domain software. Their
      paper, "Making the most of statistical analyses: improving interpretation and
      presentation." and the corresponding software, Clarify (Tomz et al., 1999) are
      the basic sources. The use of statistical simulation has become a standard
      practice with the advent of fast and low cost modern computing. The reader can
      appreciate the usefulness in biomedical research of Clarify. It can be of much
      help on the statistical analysis of many biomedical problems.

PMID- 11293893
TI  - [Development of a tool for evaluating conflict management and sexual negotiation:
      a contribution to the fight against HIV/AIDS among women].
AB  - The development and validation process of the Video Rating Scale of Conflict
      Management and Sexual Negotiation (EAVI) is presented. This instrument was
      developed as a response to the growing incidence of HIV/AIDS infection among
      heterosexual women and recognizes the need to evaluate prevention efforts that
      focus on the development of sexual negotiation skills. EAVI was used to evaluate
      taped simulations of couples negotiating safer sex. Content validity and
      reliability analysis were performed. Overall, the scale has a content validity
      score of .90 and a reliability of 75%. The validity and reliability of specific
      subscales was low thus suggesting a need for revision. Suggestions are provided
      for improving the measure and examples of its actual usefulness in academic and
      community settings are presented.

PMID- 11293894
TI  - The search for meaningful prognostic markers in diffuse large B-cell lymphoma.

PMID- 11293895
TI  - Somatic but not germline mutation of the APC gene in a case of cribriform-morular
      variant of papillary thyroid carcinoma.
AB  - We report a case of cribriform-morular variant (C-MV) of papillary thyroid
      carcinoma (PTC) in a 27-year-old woman. In addition to conventional cytologic
      features of typical PTC, the fine-needle aspirate showed numerous epithelial
      cells with abundant, eosinophilic, very elongated cytoplasm. Microscopically, the
      tumor was encapsulated and highly cellular and exhibited a mixture of cribriform,
      follicular, papillary, trabecular, solid, and spindle cell patterns of growth,
      with morular foci showing peculiar nuclear clearing (biotin-rich nuclei). The
      cells were cuboidal or tall, with frequent nuclear pseudostratification and
      abundant eosinophilic cytoplasm. The nuclei were usually hyperchromatic, with
      grooving, pallor, and pseudoinclusions. Angioinvasion and foci of capsular
      invasion were observed. Immunohistochemically, the neoplastic cells showed
      reactivity for thyroglobulin, epithelial membrane antigen, low- and high
      molecular-weight cytokeratins, vimentin, neuron-specific enolase, CD15, estrogen
      and progesterone receptors, and bcl-2 protein. Molecular genetic analysis of the
      APC gene revealed a mutation in exon 15 at codon 1309 in tumoral tissue but not
      in peripheral lymphocytes. These findings support a relationship between the
      morphologic pattern of the C-MV of PTC and the APC gene and the existence of this
      variant as a sporadic counterpart of familial adenomatous polyposis-associated
      thyroid carcinoma.

PMID- 11293896
TI  - Increased enterocyte apoptosis and Fas-Fas ligand system in celiac disease.
AB  - Our aim was to evaluate whether increased enterocyte apoptosis was responsible
      for mucosal flattening in celiac disease (CD), and, since the mechanisms
      responsible for tissue injury in this condition are unknown, we studied the
      possibility that the Fas-Fas ligand (FasL) system may be involved. Endoscopic
      duodenal biopsy specimens from 12 patients with untreated and 12 with treated CD
      and 12 control subjects were evaluated for enterocyte apoptosis by the terminal
      deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick
      end labeling assay and for Fas and FasL expression by immunohistochemistry. A
      coculture of isolated enterocytes (targets) and purified lamina propria
      mononuclear cells (LPMCs) (effectors) was performed in the absence or presence of
      an antagonistic ZB4 anti-Fas antibody. We found a significant correlation between
      the degree of villous atrophy, morphometrically evaluated, and the level of
      enterocyte apoptosis, suggesting that mucosal flattening is a consequence of
      exaggerated epithelial cell death. Most celiac enterocytes express Fas, and LPMCs
      express FasL. The abolishment of enterocyte apoptosis observed in the presence of
      ZB4 antibody suggests that enterocytes are potential targets of lymphocyte
      infiltrate. These results directly demonstrate that FasL-mediated apoptosis is a
      major mechanism responsible for enterocyte death in CD.

PMID- 11293897
TI  - Comparison of HER2/neu status assessed by quantitative polymerase chain reaction
      and immunohistochemistry.
AB  - We prospectively evaluated a series of 254 breast cancers by quantitative
      polymerase chain reaction (PCR) and immunohistochemistry using 3 antibodies:
      HercepTest, CB11, and TAB250. DNA was extracted from a 10-micron tumor section
      for PCR, and 4-micron serial sections were taken from the same block for
      immunohistochemistry. The immunohistochemical results were scored using a
      semiquantitative immunohistochemical system. A positive tumor by
      immunohistochemistry had a score of 5 or more. The manufacturer's recommended
      scoring system was used for the HercepTest. Tumors were positive for gene
      amplification if the ratio of the HER2/neu gene to control gene after
      normalization was 2 or more. Of 254 cases, 61 showed gene amplification. For
      immunohistochemistry, 23% of tumors were positive with CB11, 27% with TAB250, and
      37% with the HercepTest. Results for each antibody were compared with PCR
      results. The overall concordance for the HercepTest was 82%, which was
      significantly lower than that for CB11 (88%) or TAB250 (87%). The specificity for
      the HercepTest was 80% compared with 90% for TAB250 and 93% for CB11, while the
      positive predictive value for the HercepTest was 57% compared with 71% and 76%
      for TAB250 and CB11, respectively.

PMID- 11293898
TI  - Quality assurance in gynecologic cytology. The value of cytotechnologist
      cytopathologist discrepancy logs.
AB  - We describe a simple method for displaying and evaluating the concordance or
      discordance between cytotechnologists (CTs) and cytopathologists (CPs) on
      gynecologic cases. The provisional diagnoses made by the CTs and the final
      diagnoses of the CPs are captured by the laboratory information system; data
      generated for specified periods are displayed as a 10 x 10 matrix that classifies
      each possible diagnosis made by the CT and CP into 1 of 10 major categories.
      Matrices are generated for the entire laboratory and for individual CTs;
      individual CTs are evaluated based on their deviation from the laboratory
      average. Three statistical measures are generated: percentage of discordant
      diagnoses, a kappa statistic, and a weighted measure. During a 2.5-year period,
      approximately 4,200 cases were referred to a CP for review every 6 months. The
      median discordance in diagnoses increased during 2 years from 21% to 34%, and the
      kappa value fell from 0.69 to 0.38. This was attributed primarily to 1 CT, whose
      performance, as well as that of the entire laboratory, improved after remedial
      action. Measures of CT-CP diagnostic concordance are a useful and efficient
      measure of CT performance and can be incorporated into mandatory semiannual
      performance evaluations.

PMID- 11293899
TI  - Expression of membrane-type 1, 2, and 3 matrix metalloproteinases messenger RNA
      in ovarian carcinoma cells in serous effusions.
AB  - We studied the levels of matrix metalloproteinase (MMP)-2, membrane-type (MT)1
      MMP, MT2-MMP, and MT3-MMP in 43 malignant pleural and peritoneal effusions using
      reverse transcription-polymerase chain reaction (RT-PCR) and cellular
      localization of MT1-MMP in 66 effusion specimens and 85 corresponding primary and
      metastatic tumors using messenger RNA (mRNA) in situ hybridization (ISH). In 43
      effusions, MMP-2 mRNA was detected in 37, MT1-MMP in 25, and MT2-MMP in 32.
      Expression of MT1-MMP and MT2-MMP was found in 21 specimens; in 16 MT-MMP
      positive specimens, mRNA for only 1 of 2 enzymes was expressed. MT3-MMP mRNA was
      not detected. High levels of MMP-2 mRNA were detected more often in effusions
      with high MT1-MMP and/or MT2-MMP mRNA expression. Using ISH, MT1-MMP mRNA was
      localized to cancer cells in 27 of 58 malignant effusions; focal signals were
      detected in mesothelial cells in 7 of 42. MT1-MMP was localized to tumor cells in
      32 of 85 primary and metastatic solid lesions, and stromal cells expressed MT1
      MMP in 3. Tumor cell MT1-MMP expression in effusion specimens did not differ from
      primary or metastatic lesions. MT-MMP expression in tumor cells in effusions
      showed no association with effusion site or tumor type using ISH and RT-PCR.

PMID- 11293900
TI  - Cellular chimerism of the lung after transplantation. An interphase cytogenetic
      study.
AB  - The present study evaluated the origin of endothelial and epithelial cells, as
      well as of lymphocytes and macrophages, after lung transplantation. Biopsy
      specimens from patients who underwent lung and heart-lung transplantation and
      received organs of sex-mismatched donors were studied by means of nonisotopic in
      situ hybridization with DNA probes of the X and Y chromosome. By means of
      monoclonal antibodies against leukocytes, T and B lymphocytes, and macrophages,
      the various infiltrating cell types were analyzed. In all allografted lungs, the
      endothelial cells and bronchial and alveolar epithelium retained the donor sex
      type. The lymphocytes of the donor were almost completely replaced by recipient
      cells 1 month after transplantation. Low numbers of alveolar macrophages of the
      donor were present during the entire period under study. Low numbers of donor
      lymphocytes and high numbers of donor alveolar macrophages in the allografted
      lung seem to be correlated with a worse clinical course.

PMID- 11293901
TI  - E-cadherin reactivity of 95 noninvasive ductal and lobular lesions of the breast.
      Implications for the interpretation of problematic lesions.
AB  - Studies suggest that E-cadherin is useful to classify epithelial breast lesions
      as ductal or lobular, but extensive experience with this antibody is lacking. We
      studied reactivity of lesions with classic and indeterminate morphologic
      features. We reviewed 95 lesions and divided them into unanimous and nonunanimous
      diagnosis groups; the unanimous group served as benchmark lesions to which E
      cadherin reactivity could be standardized and compared. All 37 ductal lesions in
      the unanimous group had strong, diffuse E-cadherin reactivity. Two of 22 classic
      lobular carcinoma in situ (LCIS) lesions had sparse E-cadherin-reactive lobular
      cells within a few terminal duct lobular units. Neither displayed transition from
      nonreactive to reactive cells. Of 36 lesions in the nonunanimous group, 19 had
      insufficient morphologic features for definitive classification. Only 6 of 19
      were E-cadherin reactive, including several minimally proliferative lesions. The
      other 17 lesions in the nonunanimous group had LCIS and ductal carcinoma in situ
      (DCIS) features. All had no E-cadherin, or strong membrane reactivity of
      constituent cells in varying proportions, without a transition between reactive
      and nonreactive cells. Results suggest that the majority of morphologically
      nondiagnostic atypical lesions are lobular, including those associated with DCIS.
      E-cadherin seems to be absent in most lobular lesions.

PMID- 11293902
TI  - CD137 expression in tumor vessel walls. High correlation with malignant tumors.
AB  - CD137 (ILA/4-1BB), a member of the tumor necrosis factor receptor family, and its
      ligand are expressed on activated T lymphocytes and on antigen-presenting cells,
      respectively. Via bidirectional signal transduction, this receptor-ligand system
      regulates the activation, proliferation, and survival of T and B lymphocytes and
      monocytes. We used immunohistochemical studies on human tissue samples to
      determine in vivo CD137 expression in nonimmune tissue samples. Strong CD137
      expression was found in blood vessel walls, on the endothelial layer, and on the
      vascular smooth muscle cells. But in 32 healthy tissue samples examined, none
      contained CD137-positive vessels. Also, in benign tumors (2/14) and in
      inflammatory tissues (2/9) only a minority had CD137-expressing vessels. However,
      malignant tumors had a significantly enhanced frequency of CD137-expressing blood
      vessels (11/34).

PMID- 11293903
TI  - Realistic pathologic classification of acute myeloid leukemias.
AB  - Most classification systems of acute myeloid leukemia (AML) rely largely on the
      criteria proposed by the French-American-British (FAB) Cooperative Group. The
      recently proposed World Health Organization (WHO) classification of neoplastic
      diseases of the hematopoietic and lymphoid tissues includes a classification of
      AMLs. The proposed WHO classification of AMLs includes traditional FAB-type
      categories of disease, as well as additional disease types that correlate with
      specific cytogenetic findings and AML associated with myelodysplasia. This system
      includes a large number of disease categories, many of which are of unknown
      clinical significance, and there seems to be substantial overlap between disease
      groups in the WHO proposal. Some disease types in the WHO proposal cannot be
      diagnosed without detailed clinical information, or they are diagnosed only by
      the cytogenetic findings. In this report, a realistic pathologic classification
      for AML is proposed that includes disease types that correlate with specific
      cytogenetic translocations and can be recognized reliably by morphologic
      evaluation and immunophenotyping and that incorporates the importance of
      associated myelodysplastic changes. This system would be supported by cytogenetic
      or molecular genetic studies and could be expanded as new recognizable
      clinicopathologic entities are described.

PMID- 11293904
TI  - Primary endometrial T-cell lymphoma. A case report.
AB  - Primary lymphomas of the female genital tract are rare. Most involve the cervix
      rather than the uterine corpus. All of those previously reported have been B-cell
      lymphomas, with the exception of 1 case report of an endometrial T-cell lymphoma
      in a Japanese woman. We report the case of a white woman from the United States
      with a diffuse large cell lymphoma of the endometrium, characterized as a
      peripheral T-cell type on the basis of immunophenotypic and molecular probe
      studies. Staging evaluation revealed tumor limited to the endometrium (stage IE).
      The patient underwent a total abdominal hysterectomy, bilateral salpingo
      oophorectomy, and lymph node dissection and received 6 cycles of combination
      chemotherapy, after which she remained free of disease at last follow-up of 36
      months. Unusual features of this lymphoma case are discussed, with emphasis on
      differential diagnosis and speculation on histogenesis. This case illustrates
      that, while most peripheral T-cell lymphomas are widely disseminated at
      presentation, those limited to a single extranodal site may have a favorable
      outcome akin to that associated with high-grade extranodal B-cell lymphomas of
      early stage.

PMID- 11293905
TI  - Platelet satellitism as presenting finding in mantle cell lymphoma. A case
      report.
AB  - Platelet satellitism surrounding polymorphonuclear neutrophils has been observed
      almost exclusively in EDTA-treated blood at room temperature. The mechanism
      underlying this phenomenon is not understood fully. We report a case of platelet
      rosetting around atypical lymphocytes in peripheral blood smears made from EDTA
      treated and untreated blood. Flow cytometry of the peripheral blood sample and
      immunohistochemical stains of the subsequent bone marrow biopsy specimen revealed
      a monoclonal B-cell population positive for CD5, CD20, and cyclin D1 and negative
      for CD3 and CD23; cytogenetic findings revealed a complex karyotype that included
      t(11;14). These findings were consistent with mantle cell lymphoma. To our
      knowledge, the finding of platelet satellitism involving mantle cell lymphoma
      cells in peripheral blood has not been reported previously.

PMID- 11293906
TI  - Mature B-cell leukemias with more than 55% prolymphocytes. A heterogeneous group
      that includes an unusual variant of mantle cell lymphoma.
AB  - We studied 20 cases of mature B-cell leukemia with more than 55% prolymphocytes
      in peripheral blood or bone marrow, fulfilling the French-American-British
      criteria for B-cell prolymphocytic leukemia (PLL). Cases segregated into 3
      groups: de novo PLL, 6; PLL occurring in patients with a previous well
      established diagnosis of chronic lymphocytic leukemia (PLL-HxCLL), 10; and
      t(11;14)(q13;q32)-positive neoplasms, 4. All cases expressed monotypic
      immunoglobulin light chain, and most were positive for CD5. All t(11;14)-positive
      neoplasms were CD23- and uniquely positive for cyclin D1. Cytogenetic
      abnormalities were present in 19; in all 19, the karyotype was complex,
      indicating clonal evolution and genomic instability. The most frequent
      cytogenetic abnormality in de novo PLL involved chromosome 7 in 4 cases. Trisomy
      12 or add(12p) was present in 4 cases of PLL-HxCLL. We conclude that mature B
      cell leukemias with more than 55% prolymphocytes are a heterogeneous group that
      includes t(11;14)-positive neoplasms, which we suggest are best classified as
      mantle cell lymphoma. We also suggest that prolymphocytic morphologic features
      are a common end-stage of transformation for several B-cell neoplasms.

PMID- 11293907
TI  - The clinical significance of CD10 antigen expression in diffuse large B-cell
      lymphoma.
AB  - The clinical significance and prognostic value of CD10 in de novo diffuse large B
      cell lymphoma (DLBCL) is largely unknown. We retrospectively studied 19 men and 9
      women based on the following criteria: (1) DLBCL with no evidence of concomitant
      or antecedent follicular lymphoma; (2) available flow cytometric
      immunophenotyping data, including CD10 status; (3) older than 15 years; (4)
      specific exclusion of high-grade, Burkitt-like lymphoma; and (5) exclusion of
      primary cutaneous DLBCL. When available, clinical data at diagnosis, including
      components of the international prognostic index, were reviewed. Eleven cases
      were CD10+, and 17 were CD10-. There was no significant difference between the
      CD10+ and CD10- groups in age, sex, stage, performance status, extranodal
      involvement, or serum lactate dehydrogenase levels at diagnosis. However, in the
      26 cases for which follow-up data were available, the CD10+ group displayed a
      shorter overall survival than the CD10- group (8 vs 30 months). Although the
      clinical findings at diagnosis are similar in CD10+ and CD10- DLBCL, CD10
      expression is associated with shortened overall survival. Therefore, our data
      suggest CD10 expression may have prognostic importance in adults with de novo
      DLBCL.

PMID- 11293908
TI  - Interdigitating dendritic cell sarcoma. A report of four cases and review of the
      literature.
AB  - To better define the clinical and pathologic features of interdigitating
      dendritic cell sarcoma (IDCS), we report 4 cases, including the first reported in
      the tonsil. There were 2 male and 2 female patients (mean age, 70 years). Sites
      of tumor included 1 case each in the right cervical lymph node, left axillary
      lymph node, right tonsil, and right inguinal lymph node. Histologically, all
      showed diffuse effacement of the lymphoid tissue by pleomorphic round to spindled
      cells with convoluted nuclei and abundant eosinophilic cytoplasm. All were
      immunoreactive for S-100, CD68, lysozyme, and vimentin. CD45 was positive in 3
      cases and CD1a in 1 case. Fascin was positive in 3 cases. Other immunostains,
      including CD3, CD20, CD21, CD30, actin, cytokeratin, and HMB-45, were negative.
      Ultrastructurally, the tumor cells were elongated and showed indented nuclei,
      variable numbers of lysosomes, and interdigitating cytoplasmic processes. Follow
      up was available for all cases. One patient died of widespread disease 2 months
      after diagnosis. One was alive with metastatic lung disease at 12 months. Two
      patients were disease free at 5 and 9 months.

PMID- 11293909
TI  - Digoxin-like and digitoxin-like immunoreactive substances in elderly people.
      Impact on therapeutic drug monitoring of digoxin and digitoxin concentrations.
AB  - We compared digoxin-like (DLIS) and digitoxin-like (DTLIS) immunoreactive
      substance concentrations for 30 people older than 65 years with those for 25
      people younger than 50. None received digoxin or had liver disease, uremia, or
      volume expansion. We found no DTLIS in any specimen, and only 1 specimen from an
      elderly person demonstrated a low DLIS concentration. In addition, for 22 non
      volume expanded patients (8 younger than 50 years and 14 older than 65) receiving
      digoxin, the fluorescence polarization (FPIA) and the microparticle enzyme (MEIA)
      immunoassays revealed comparable serum digoxin concentrations, indicating an
      insufficient DLIS concentration to interfere with digoxin immunoassay results.
      Therefore, elderly people who are not volume expanded do not have elevated DLIS
      or DTLIS concentrations. Furthermore, for patients with liver disease or uremia
      (18 older than 65 years and 20 younger than 50), the DLIS and DTLIS
      concentrations were elevated. Finally, for 5 patients with liver disease who
      received digoxin, serum digoxin concentrations were lower by MEIA and higher by
      FPIA, indicating the patients had elevated DLIS levels that interfered with the
      assays. Elevated DLIS and DTLIS concentrations are associated with volume
      expansion and not age.

PMID- 11293910
TI  - Automated urinalysis. Evaluation of the Sysmex UF-50.
AB  - We assessed the Sysmex UF-50 for reproducibility of results and carryover rate by
      performing between- and within-run precision analyses on 315 urine samples,
      evaluated the feasibility of using the UF-50 to measure urinary cellular and
      noncellular components by comparing results from the UF-50 with results of manual
      urinalysis using the Kova system, and performed side-by-side comparison of the
      within-run reproducibility from the UF-50, the UF-100, and the Kova system.
      Results from the UF-50 and UF-100 were highly reproducible, and the carryover
      rate was 0.5% or less for the urinary components. In between-run precision
      assays, the coefficients of variation for UF-50 results for all cellular
      components were less than 10%. The agreement (gamma statistics) between values
      from the UF-50 and the Kova system was excellent for RBC, WBC, and bacterial
      counts. The cell counts from the UF-50 for RBCs, WBCs, epithelial cells, and
      bacteria were 52%, 63%, 54%, and 110%, respectively, of those measured by manual
      urinalysis. The UF-50 performed quantitative analysis in 72 seconds, compared
      with 330 seconds for manual methods. The UF-50 is suitable for the first
      screening to detect hematuria, pyuria, and bacteriuria.

PMID- 11293911
TI  - Special studies help diagnose intestinal spirochetosis in HIV-positive patients.

PMID- 11293912
TI  - Lowenstein-Jensen media no longer necessary: too strong a statement?

PMID- 11293913
TI  - Motor skills of typically developing adolescents: awkwardness or improvement?
AB  - To identify sex differences and developmental trends in motor performance and
      coordination across three stages of development: prepubertal, pubertal and
      postpubertal, 60 participants, 30 males and 30 females, were assessed on 13 motor
      tasks. Physical characteristics that accompany puberty were used to classify the
      participants into the stages. Analysis of variance and covariate analyses
      demonstrated that motor performance improves throughout adolescence in both males
      and females and that sex differences exist in motor performance, males performing
      better than females. The magnitude of the stage and sex differences were
      demonstrated by large effect sizes (eta 2). The motor tasks of long jump, running
      speed, and throwing a ball principally distinguished between the males and
      females. Female performance differed less from male performance after puberty.
      Results showed no.

PMID- 11293914
TI  - Comparison of the motor development of school-age children born to mothers with
      and without diabetes mellitus.
AB  - The objectives of this study were to examine the effects of diabetes during
      pregnancy on the long-term motor development of the offspring and to study
      possible correlations between glycemic control and motor development. We compared
      the motor development of 57 children, 5- to 12-years-of-age, born to 48 mothers
      with well-controlled diabetes, to the motor development of 57 control children
      matched by age, birth order, and parental socio-economic status. Children born to
      mothers with diabetes performed less well than controls in fine and gross motor
      functions on the Bruininks-Oseretsky Test of Motor Proficiency. A negative
      correlation existed between the test scores of the children whose mothers had
      diabetes and the severity of hyperglycemia as assessed by blood glycosylated
      hemoglobin levels and acetonuria. Motor ability of the children of mothers with
      diabetes had a high correlation with biological and environmental variables.
      These results suggest that diabetes during pregnancy may affect the developing
      brain, inducing long-term mild motor deficiency. The effects seem to result from
      the adverse effects of diabetic metabolic factors, and the effects correlate with
      the degree of diabetes control. The combination of metabolic functioning of women
      with diabetes and home environment may affect the motor development of their
      children.

PMID- 11293915
TI  - Concurrent validity of the Bayley Scales of Infant Development II Motor Scale and
      the Peabody Developmental Motor Scales in two-year-old children.
AB  - Concurrent validity of the Bayley Scales of Infant Development, Second Edition
      (BSID II) Motor Scale and the Peabody Developmental Motor Scales (PDMS) was
      examined by administering both tests to 38 two-year-old Native American children.
      A correlation analysis of age equivalent scores indicated very good to high
      correlation for the BSID II Motor Scale with the PDMS Fine Motor Scale (PDFMS) (r
      = .87) and the PDMS Gross Motor Scale (PDGMS) (r = .83). A correlation analysis
      of standard scores showed poor to unacceptable correlation between the BSID II
      Motor Scale with the PDFMS (r = .64) and the PDGMS (r = .49); further, there was
      poor agreement between the classifications of significantly delayed, mildly
      delayed, and within normal limits performance on each test. The PDFMS tended to
      classify children lower than the BSID II Motor Scale. The scores of the
      relatively younger children within each of the PDMS 6-month age categories agreed
      less between the tests than did the scores of the relatively older children. In
      conclusion, this study provides evidence for the concurrent validity of the BSID
      II Motor Scale and the PDMS for age equivalent scores, but not for standard
      scores of 2-year-old children. Professionals must be aware of the strengths and
      limitations of the BSID II and the PDMS, and choose appropriately to avoid denial
      of or over-referral for services for young children.

PMID- 11293916
TI  - Conducting an inventory of informal community-based resources for children with
      physical disabilities: enhancing access and creating professional linkages.
AB  - This article describes the process involved in conducting a sample inventory of
      community-based sports, recreation/leisure, and arts resources that include
      children with physical disabilities in Monroe County, New York. The inventory
      instrument, Community Resource Inventory for Children with Physical Disabilities,
      was designed to examine organizational or group capacity to provide activities
      for children with physical disabilities. The inventory was administered by phone
      to organizations and groups identified as meeting the definition of a community
      based resource. One hundred and six CBR informants were interviewed, each
      reporting one or two recreational activities provided at their site. The
      activities included arts, sports, or leisure offerings, with a total of 127
      activities identified in the sample. The results of the study support the premise
      that community-based resources are receptive to providing activities for children
      with physical disabilities and to potential collaboration with therapists.
      Numerous barriers exixts, however, including environmental inaccessibility, lack
      of personnel training, and including environmental inaccesssbility, lack of
      personnel training, and costs of participation. The results suggest several
      educational and system-based changes that may promote future collaborative
      efforts between therapists and community-based organizations.

PMID- 11293917
TI  - Caught in the Web.

PMID- 11293918
TI  - Serum activin A levels in males and females during pubertal development.
AB  - Activin A is a dimeric protein composed of two beta A-subunits protein of the
      transforming growth factor-beta (TGF-beta) family. This protein is synthesized by
      a variety of organs. A sensitive and specific assay for bioactive dimeric activin
      A has recently been developed, to measure circulating levels in adult women and
      men, giving a new insights into the possible physiological role of this protein
      in the reproductive axis and/or in other functions. The aim of the present study
      was to evaluate serum dimeric activin A levels in boys and girls during pubertal
      development. The study was performed on a group of children (n = 54) aged between
      6 and 18 years at different Tanner stages. Serum levels of activin A were
      measured using a specific and sensitive two-site ELISA. Serum activin A levels
      were not significantly different at various Tanner stages (Tanner I, 0.36 +/-
      0.02 ng/ml; Tanner II, 0.33 +/- 0.02 ng/ml; Tanner III, 0.35 +/- 0.03 ng/ml;
      Tanner IV, 0.41 +/- 0.04 ng/ml; Tanner V, 0.35 +/- 0.05 ng/ml; p > 0.01). No
      difference between male and female children was observed. In conclusion, the lack
      of significant differences in activin A serum levels according to the Tanner
      stages or to gender demonstrates that this protein is not involved in the
      endocrine modifications during pubertal development and that its measurement may
      not provide a sensitive new tool for determining gonadal maturity at puberty.

PMID- 11293919
TI  - Plasma beta-endorphin levels in obese and non-obese patients with polycystic
      ovary disease.
AB  - The aim of this study was to determine the influence of body weight on
      circulating plasma levels of beta-endorphin and insulin in women with polycystic
      ovary disease (PCOD), as well as the correlation between the plasma levels of
      beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with
      PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) < 25)
      while 50 were obese (BMI > 25). A venous blood sample was taken and plasma
      concentrations of beta-endorphin, insulin, gonadotropins, prolactin,
      progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone
      sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta
      endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese
      PCOD women than in non-obese ones. Correlation analysis showed a positive
      association between insulin and beta-endorphin, beta-endorphin and BMI (and
      weight), insulin and BMI (and weight), and a negative correlation was found
      between insulin and SHBG. A weak association was found between beta-endorphin and
      luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression
      analysis showed that plasma beta-endorphin concentrations correlate more with BMI
      than with insulinemia.

PMID- 11293920
TI  - The evidence for an etiological relationship between oral contraceptive use and
      dysplastic change in cervical tissue.
AB  - A case-control study of 112 patients with cervical intraepithelial neoplasia
      (CIN) and 131 control subjects was conducted. Estradiol receptor levels were
      determined in the total (cytosolic-nucleosolic) fraction of the neoplastic
      cervical specimens taken during the late proliferative phase of their cycle from
      58 premenopausal patients who had been oral contraceptive (OC) users for at least
      2 years and from 54 premenopausal women who had not been OC users. All specimens
      contained variable amount of estradiol receptor (from 7.6 to 53.0 fmol
      estradiol/mg protein and 7.2 to 29.3 fmol estradiol/mg protein in patients who
      were OC users and non-users, respectively). A significant correlation was found
      between estradiol receptor concentration and histological grading in both groups,
      likewise higher levels of estradiol receptor were observed in the low-grade CIN
      group tissue from patients who were OC users (p < 0.05). At the same time 17 beta
      estradiol and progesterone levels were also determined in the serum of all women
      who had not used an OC for at least 12 months. The mean +/- SD estradiol serum
      levels in non-users of OC with CIN (0.189 +/- 0.08 ng/ml, follicular phase) were
      greater than the mean +/- SD (1.163 +/- 0.33 ng/ml, luteal phase) progesterone
      serum concentration. Serum estradiol levels were significantly higher (p < 0.05)
      in OC users, whereas progesterone levels were not (p > 0.05). OC users had an
      increased risk (odds ratio = 1.31, 95% CI 1.0-2.3) of cervical neoplasia.

PMID- 11293921
TI  - Soluble L-selectin levels during controlled ovarian hyperstimulation.
AB  - We sought to determine whether neutrophil activation, as reflected by soluble L
      selectin levels, plays a role in controlled ovarian hyperstimulation (COH) and
      the possible correlation between soluble L-selectin and serum sex steroid levels.
      The study population consisted of 14 consecutive patients undergoing our routine
      in vitro fertilization (IVF) long gonadotropin-releasing hormone (GnRH) analog
      protocol. Blood was drawn three times during the COH cycle: (1) on the day when
      adequate suppression was obtained (Day-S); (2) on the day of, or the day prior
      to, human chorionic gonadotropin (hCG) administration (Day-hCG); and (3) on the
      day of ovum pick-up (Day-OPU). Levels of sex steroids and plasma soluble
      leukocyte selectin (L-selectin) were compared among the three time points.
      Soluble L-selectin was measured with a commercial sandwich enzyme-linked
      immunosorbent assay (ELISA). The results showed significantly higher levels of
      soluble L-selectin on Day-OPU than on Day-S and Day-hCG, and significantly lower
      levels on Day-hCG than Day-S. Though no significant correlations were found
      between soluble L-selectin and serum estradiol or hCG levels, soluble L-selectin
      positively correlated with serum progesterone levels. We conclude that hCG
      administration leads to neutrophil activation, which correlates with the degree
      of luteinization. Further studies are required to elucidate the relationship
      between the immune system and COH. These may lead to new strategies for
      predicting and preventing complications of COH.

PMID- 11293922
TI  - Effects of nitric oxide donors on the contractility and prostaglandin synthesis
      of myometrial strips from pregnant and non-pregnant women.
AB  - Nitric oxide (NO) is a potent relaxant of smooth muscle and possibly plays a role
      in maintaining uterine quiescence during pregnancy. Clinical studies have shown
      beneficial effects of the stable NO donor glyceryl trinitrate (GTN) for the
      inhibition of pathological myometrial contractility that occurs in preterm labor
      or dysmenorrhea. Since there are contradictory results regarding the mediation of
      the relaxing effect of NO, the myometrial prostaglandin synthesis during
      superfusion with NO donors was studied. Human myometrial strips obtained either
      at term Cesarean sections before the onset of labor or after hysterectomies in
      premenopausal women were studied in a superfusion system. After the manifestation
      of spontaneous contractions, GTN was added in low doses comparable with in vivo
      levels (0.4-40 nM) and the effect on myometrial activity, intracellular cGMP and
      prostaglandin production was analyzed. Additionally, the effect of sodium
      nitroprusside (SNP)--which releases NO spontaneously--was compared with that of
      GTN. GTN caused a significant decrease in the contraction frequency of myometrial
      strips from both pregnant and non-pregnant women similar to that of SNP. There
      was no significant change in the myometrial synthesis of PGI2, PGF2 alpha and
      PGE2, whereas the intracellular cGMP content was increased. In conclusion, GTN
      showed a significant inhibitory effect on human myometrium in vitro in very low
      doses and therefore represents an interesting therapeutic alternative for the
      treatment of preterm labor and dysmenorrhea. GTN in low doses did not alter the
      prostaglandin synthesis of human myometrium.

PMID- 11293923
TI  - Effects of hyperprolactinemia on osteoporotic fracture risk in premenopausal
      women.
AB  - The aim of the study was to evaluate the osteoporotic fracture risk in
      premenopausal women with hyperprolactinemia due to prolactinoma. Bone mineral
      density (BMD) was measured in 20 white, premenopausal women with prolactinoma and
      in 60 healthy control white women, using quantitative ultrasound (QUS) at the os
      calcis, with an Achilles Lunar Plus device. We measured all three parameters of
      QUS: broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness.
      BMD results were expressed also as T- and Z-scores. Age and body mass index (BMI)
      were not statistically significantly different between the two groups.
      Comparative analysis showed reduced values of QUS parameters in women with
      prolactinoma versus controls. Only the difference in SOS parameter was
      statistically significant between the two studied groups (p = 0.0001). The Z
      score was significant lower in women with prolactinoma than in healthy women.
      These data reveal a significant bone loss in women with prolactinoma compared to
      controls. The SOS parameter showed a good negative correlation with age, and all
      the QUS parameters were positively correlated with BMI. The relative risk for
      developing osteoporosis in women with prolactinoma was found to be 4.5,
      indicating that hyperprolactinemia in women is a major risk factor for
      osteoporosis.

PMID- 11293924
TI  - Effect of trimegestone alone or in combination with estradiol on bone mass and
      bone turnover in an adult rat model of osteopenia.
AB  - The effects of trimegestone (1 mg/kg/day orally), a novel norpregnane progestin,
      and 17 beta-estradiol (10 micrograms/kg/day subcutaneously), alone and in
      combination, on bone mass and turnover were investigated using an experimental
      model of osteoporosis involving ovariectomized rats. An equivalent dose (1
      mg/kg/day orally) or norethisterone was used as a reference progestin. Six-month
      old rats were ovariectomized and left untreated for 2 months to allow the
      development of osteopenia. Treatment with a progestin, alone or in combination
      with estradiol, was then started and continued for 2 months. Bone was assessed by
      a combination of static and dynamic histomorphometric measurements, by
      densitometry and by the use of biochemical markers of bone turnover. Ovariectomy
      induced a pronounced uterine atrophy, which was reversed by estradiol.
      Trimegestone effectively counteracted the uterotropic effect of estradiol, whilst
      norethisterone showed a less pronounced antagonistic effect. A severe osteopenia
      was established in the initial 2 months after ovariectomy, and further bone loss
      occurred during the 2-month treatment period in animals not receiving estradiol.
      This effect was associated with a marked increase in both biochemical and dynamic
      histomorphometric markers of bone turnover, reflecting in an imbalance between
      resorption and formation. 17 beta-estradiol given alone prevented further bone
      loss, but neither trimegestone nor norethisterone alone had a beneficial effect
      on bone mass and turnover. When given in combination with 17 beta-estradiol,
      however, trimegestone significantly improved its effect on bone mass and
      turnover. This effect was more potent than that induced by combined 17 beta
      estradiol and norethisterone therapy. We conclude that trimegestone, when
      combined with 17 beta-estradiol, is a more effective progestin than
      norethisterone in preventing bone loss in adult ovariectomized rats.

PMID- 11293925
TI  - Hormonal activity of transposed ovaries in young women treated for cervical
      cancer.
AB  - The purpose of this study was to assess the hormonal function of transposed
      ovaries in young women treated for cervical cancer. Between 1992 and 1998, in the
      Silesian Medical Academy in Bytom, 101 women underwent radical hysterectomy with
      ovarian transposition by the Wertheim-Meigs method. Concentrations of follicle
      stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol and
      testosterone in blood serum and cytologic indices (maturation index,
      karyopyknotic index and maturation value) were assessed before surgery and on the
      ninth day after surgery. Patients were subsequently requested to return in July
      1999 to have the hormonal activity of their ovaries assessed from the perspective
      of a few years after the operation, and the effect of supplementary radiotherapy
      soon after surgery. There was a statistically significant difference between
      those who had radiotherapy and those who did not with respect to climacteric
      complaints and hormonal parameters. A correlation was found between serum
      estradiol levels and maturation value. Proper ovarian hormonal function was still
      present in 69.8% of patients, even 60 months after surgery, but a lower bone
      mineral density was also observed. Ovarian transposition is a procedure that
      allows ovarian function to be preserved in young women treated for cervical
      cancer; it also helps to obviate the necessity for long-term hormone-replacement
      therapy. However attention must be paid to the concomitant possibility that women
      with cervical cancer may have a lower bone mineral density, and routine follow-up
      measurement of FSH levels or cytologic indices is advocated.

PMID- 11293926
TI  - Influence of daily calcium and vitamin D supplementation on parathyroid hormone
      secretion.
AB  - Calcium and vitamin D supplementation have been shown to reduce secondary
      hyperparathyroidism and play a role in age-related osteoporosis. In order to
      define the optimal regimen of calcium and vitamin D supplementation to produce
      the maximal inhibition of parathyroid hormone secretion, we compared the
      administration of a calcium-vitamin D supplement as a single morning dose with
      the administration of two divided doses at 6-hour intervals. Twelve healthy male
      volunteers were assigned to three investigational procedures, which were
      alternated at weekly intervals. After a 'blank' control procedure, when they were
      not exposed to any supplements, they received one of two calcium-vitamin D
      supplement regimens: either two doses of Orocal D3 (500 mg calcium and 400 IU
      vitamin D3) with a 6-hour interval between doses, or one water-soluble
      effervescent powder pack of Cacit vitamin D3, taken in the morning (1000 mg
      calcium and 880 IU vitamin D3). During the three procedures (control and the two
      calcium-vitamin D supplementation protocols), veinous blood was drawn every 60
      minutes for up to 9 hours, for serum calcium and parathyroid hormone
      measurements. The order of administration of the two calcium and vitamin D
      supplementation regimens was allocated by randomization. No significant changes
      in serum calcium were observed during the study. During the first 6 hours
      following calcium-vitamin D supplementation, a statistically significant decrease
      in serum parathyroid hormone was observed with both regimens, compared with
      baseline and the control procedure. During this first period, no differences were
      observed between the two treatment regimens. However, between the 6th and the 9th
      hour, serum parathyroid hormone levels remained significantly decreased compared
      to baseline with the twice-daily Orocal D3 administration, while they returned to
      baseline values with the once-daily Cacit D3 preparation. During this period, the
      percentage decrease in serum parathyroid hormone relative to baseline was
      significantly greater with Orocal D3 than Cacit D3 (p = 0.0021). We therefore
      conclude that the twice-daily administration of 500 mg calcium and 400 IU vitamin
      D3 at 6-hour intervals provides a more prolonged decrease in serum parathyroid
      hormone levels than the administration of the same total amount of calcium and
      vitamin D, as a single morning dose in young healthy.

PMID- 11293927
TI  - Endometrial patterns and endocrinologic characteristics of asymptomatic
      menopausal women.
AB  - The endometrial histology and endocrinologic and demographic characteristics of
      556 asymptomatic postmenopausal women, who attended the menopause outpatient
      clinic at Ankara Numune Education and Research Hospital were studied before
      initiating estrogen replacement therapy. Of these women, 486 (87.4%) had atrophic
      endometrium, 37 (6.65%) had proliferative endometrium, 27 (4.86%) had endometrial
      hyperplasia without atypia, three (0.54%) had endometrial hyperplasia with atypia
      and three (0.54%) had endometrial adenocarcinoma on their biopsy specimens. When
      demographic characteristics of the patients were considered, we found that the
      patients with endometrial adenocarcinoma and endometrial hyperplasia with atypia
      had potential risk factors for endometrial pathology such as chronic anovulation,
      diabetes or hypertension. This study confirms that routine endometrial sampling
      in asymptomatic postmenopausal women is not warranted, but patients with
      associated risk factors should be screened for endometrial pathology before
      starting estrogen replacement therapy.

PMID- 11293928
TI  - Estrogen improves impaired musculocutaneous vascular adrenergic reactivity in
      pharmacologically ovariectomized rats: a potential peripheral mechanism for hot
      flashes?
AB  - Hot flashes are among the most common complaints of perimenopausal women. Despite
      the high prevalence of the phenomenon, the background to the development of hot
      flashes is still not completely understood, through a hypothesized central
      mechanism, involving norepinephrine and luteinizing hormone-releasing hormone (LH
      RH) secretion is widely accepted. We studied the influence of sex steroid
      deficiency and hormone replacement therapy on the biomechanical properties of
      musculocutaneous arterioles, to see whether a peripheral mechanism also exists in
      the development of hot flashes. Fifty adult, nulliparous, non-pregnant female
      Sprague-Dawley rats received pharmacological ovariectomy, and estradiol,
      medroxyprogesterone, or both hormones. After 12 weeks the saphenous artery was
      isolated by microdissection. Norepinephrine-induced tone (active tangential
      strain) was measured as a function of intraluminal pressure in an organ bath. The
      norepinephrine-induced arterial tone was significantly different between the
      control group and the ovariectomized animals in the range of 80-150 mmHg
      intraluminal pressure (p < 0.05). Also, significant differences were found
      between the ovariectomized group and the animals receiving estradiol monotherapy
      (p < 0.01 between 80 and 170 mmHg, and p < 0.05 between 180 and 200 mmHg
      intraluminal pressure). Neither medroxyprogesterone monotherapy nor combined
      hormone replacement therapy induced significant changes in the norepinephrine
      induced vascular tone. The absence of sex steroids leads to decreased reactivity
      to norepinephrine in small musculocutaneous arteries, while chronic estradiol
      replacement therapy restores the impaired responsiveness of the vessels. Our data
      raise the possibility that in addition to the central mechanism, a previously
      unknown peripheral background mechanism for perimenopausal hot flashes may exist.

PMID- 11293929
TI  - Estrogen replacement therapy in postmenopausal women: a study of the efficacy of
      estriol and changes in plasma gonadotropin levels.
AB  - The purpose of this study was to clarify the efficacy of estriol for estrogen
      replacement therapy in postmenopausal women with undefined symptoms and to
      evaluate endocrinological changes during therapy in relation to clinical outcome.
      Administration of 2 mg estriol in 168 postmenopausal patients was markedly
      effective in 22.6% of cases, effective in 45.2%, fairly effective in 14.3%, and
      ineffective in 17.9% of cases. The plasma concentration of follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) after administration of estriol
      decreased significantly (p < 0.001), by 52.2% and 32.9%, respectively for
      markedly effective cases, and by 39.1% and 48.0% for effective cases. In
      contrast, the plasma estradiol concentration remained unchanged. On the other
      hand, decreases in FSH and LH concentration were 13.9% and 5.9% for the fairly
      effective and 8.2% and 1.9% for ineffective cases, demonstrating a significantly
      lower decrease in plasma FSH and LH levels than in the markedly effective and
      effective cases (p < 0.001). For cases showing side-effects, the plasma FSH and
      LH levels decreased by 52.0% and 64.3%, respectively, whereas the plasma
      estradiol level remained unchanged. In conclusion, the efficacy of estriol was
      significantly correlated to the degree of decrease in plasma FSH and LH levels in
      patients with undefined symptoms. In addition, efficacy appeared to be correlated
      to the incidence of side-effects. The degree of reduction of FSH (39.1-52.2%) and
      LH (48.0-64.3%) from the baseline may possibly be used as a guide to the
      therapeutic hormone levels during HRT. The present results suggest that plasma
      gonadotropin levels could be a useful indicator in the management of patients
      undergoing estrogen replacement therapy.

PMID- 11293930
TI  - Postmenarchal Down's syndrome: a theoretical model of growth hormone action on
      ovarian function.
AB  - Much evidence indicates that blunted ovarian sensitivity to follicle-stimulating
      hormone (FSH) and lower growth hormone (GH) plasma concentrations, as often occur
      in women with Down's syndrome (DS), may contribute to the gonadal disfunction
      frequently present in such subjects. In this review, we analyze the more recent
      advances in this field, and then discuss from a clinical point of view the
      potential role of GH on ovarian function, since DS patients may also constitute a
      theoretical model for investigating this particular aspect of reproductive
      physiology.

PMID- 11293931
TI  - [Healing process of uncomplicated sole ulcers in dairy cows kept in tie stalls:
      clinical description and blood chemical investigations].
AB  - A total of 74 dairy cows with 105 separate lesions were treated and the healing
      process was observed for half a year and the results compared with the
      biochemical data. The mean time for the formation of a closed layer of horn was
      25 days for lesions with slight corium alterations, 33 days for moderate and 42
      days for severe alterations. Thirty days after the initial treatment 68% of all
      lesions were completely covered by a solid layer of new horn. The further
      evaluation of the healing process was based on quality and rate of the new horn
      formation, recovery from lameness and sensitivity to hooftesters. Using these
      parameters the healing potential of exposed corium was judged one month after
      treatment with a scoring system. The 30-day-healing process was considered to be
      good in 61% and moderate to bad in 39% of the cows. The concentration of glucose,
      cholesterin, LDH and blood urea was increased in one third of the animals.
      Phosphorus and magnesium concentrations were lower than the reference values in
      30%, and 26% of the animals, respectively. Cows with prolonged healing had higher
      levels of bilirubin, creatinkinase, LDH, ALT and AST than cows with a good
      healing process. Concentration of iron, vitamin A and biotin were significantly
      lower in cows with moderate to bad healing parameters than cows with a good
      healing potential. From these results it is suggested that biochemical blood
      parameters and the vitamin status might influence the healing of uncomplicated
      sole ulcers, respectively.

PMID- 11293932
TI  - [Lead poisoning in calves due to old white lead paint].
AB  - A case of poisoning by chronic ingestion of lead in calves with a peracute
      clinical course is described. The source of lead was a prime coat of white lead
      on old white painted doors. These doors originated from an institution for aged
      people and had been used as pen walls for fattening calves. About 12 weeks later
      five animals died within hours after onset of CNS-symptoms. The post mortem
      examination of three animals revealed one with multifocal laminar edema and mild
      vasculitis in the cerebrocortex, one with acid fast intranuclear inclusion bodies
      in the renal tubular epithelial cells and one without lesions. Liver, kidney and
      abomasal contents of two animals were analysed for lead content. The
      concentration was diagnostic for lead poisoning in one case only.

PMID- 11293933
TI  - [Canine dirofilariasis in the canton of Ticino and in the neighboring areas of
      northern Italy].
AB  - The distribution of canine dirofilariosis in Southern Ticino (Switzerland) and in
      the neighbouring provinces of Varese and Como (Italy) was investigated. Blood
      samples were collected from 308 dogs which had remained in the local area and
      were outdoor-housed, older than 1.5 years and had not been treated previously
      with preventive or microfilaricidal drugs. Microfilariae of Dirofilaria immitis
      and D. repens were found in 33 (10.7%) and 17 (5.5%) dogs, respectively. Ten more
      dogs (3.2%) tested positive for circulating antigens. Four infected dogs lived in
      Southern Ticino: two harboured D. immitis, one D. repens and one had a mixed
      infection. In addition, 3887 mosquitoes were captured in five sample sites by
      means of dog-baited traps. Culex pipiens, Aedes geniculatus and Ae. vexans were
      the most abundant species. Infective stages of D. immitis were observed in local
      strains of Ae. geniculatus and Cx. pipiens, following engorgement on a
      microfilaraemic dog and the successive rearing in laboratory conditions. A chemo
      prophylactic scheme in four administrations between July and October is
      recommended for Southern Switzerland.

PMID- 11293934
TI  - [Double outlet right ventricle (DORV) in a 15 month old heifer].
AB  - The clinical findings, results of further investigations and necropsy of a 15
      month old heifer with multiple congenital heart defects are presented. The
      symptoms were caused by a high ventricle septum defect and a hypoplastic,
      completely dextroponed aorta (DORV). Hematology, radiology and ultrasonography
      findings, right heart and pulmonary blood pressure, and blood gas measurements,
      as well as electro- and phonocardiograms are presented. The consequences of the
      multiple cardiac anomalies for the pulmonary circulation are described.

PMID- 11293935
TI  - [What is your diagnosis? Psittacosis].

PMID- 11293936
TI  - [Nebivolol, a beta blocker of the 3rd generation: modern therapy of arterial
      hypertension. Results of a multicenter observation study].
AB  - BACKGROUND: Nebivolol represents a therapeutic class of beta blockers with high
      beta 1 selectivity and modulatory effect on vascular reactions by releasing
      nitric oxide (NO) from endothelial cells. Its antihypertensive effect by once a
      day application is established. The aim of the study was to investigate the
      acceptability and the antihypertensive efficacy of Nebivolol in hypertensives
      with and without concomitant diseases. METHODS AND RESULTS: An observational
      study was carried out in 6376 patients with arterial hypertension in 1529 centres
      in a period of time of six weeks. The initial dosage was 5 mg daily resp. 2.5 mg
      daily in patients over 65 years. The systolic blood pressure (BP) decreased
      during treatment from initial values of 173 +/- 18 mm Hg (mean +/- standard
      deviation) by 29 mm Hg to 144 +/- 14 mm Hg at the end of the observational
      period. The diastolic BP decreased from 101 +/- 9 mm Hg initially by 16 mm Hg to
      85 +/- 8 mm Hg at the last examination of the patients. The normalization of the
      diastolic BP (< 90 mm Hg) was achieved in 62.2% of the patients. The mean heart
      rate (HR) was 84 +/- 12 beats/minute at the beginning of the study and decreased
      by 11 to 73 +/- 8 beats/minute. During the observational period cholesterol,
      triglycerides and blood glucose showed a significant decrease (p < 0.001).
      Triglycerides were diminished by 13%, cholesterol by 8%. In diabetic patients the
      most favourable effect was observed (decrease of triglycerides by 18% and
      cholesterol by 9%); glucose decreased in diabetics by 16%. CONCLUSIONS: In this
      multicentre observational study Nebivolol was proved as a safe and well-tolerated
      antihypertensive drug. The results of the analysis of metabolic parameters during
      Nebivolol treatment are of interest as a contribution to the preventive effect of
      this beta blocker on coronary heart disease.

PMID- 11293937
TI  - [Levonorgestrel releasing intrauterine spiral--contraception and therapeutic
      indications].
AB  - The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly reliable
      contraceptive device. It is a suitable method of contraception also for breast
      feeding mothers, and for women who have completed their family it is a real
      alternative to sterilisation. In comparison with the copper-releasing
      intrauterine devices, the rates of ectopic pregnancies and adnexitis/pelvic
      peritonitis (PID) are reduced. In menstruating women the menstrual blood loss is
      lower and, correspondingly, dysmenorrhoea and/or iron-deficiency anaemia occur
      less frequently and when they do occur they are less severe. In
      hypermenorrhoea/menorrhagia the LNG-IUS is a therapeutic alternative to the
      surgical procedure. In the menopause and postmenopause the LNG-IUS is suitable
      for protection of the endometrium in women undergoing continuous estrogen
      replacement therapy.

PMID- 11293938
TI  - [Telemedicine in surgery: evidence-based?].

PMID- 11293939
TI  - [Atypical anorexia nervosa].

PMID- 11293940
TI  - [Clinical problem solving. Diarrhea in an HIV-infected patient. Stage CDC B3 HIV
      infection. Gastroenteritis with Campylobacter jejuni].

PMID- 11293941
TI  - [Dementia--the price for increased life expectancy?].

PMID- 11293942
TI  - Angioedema and antihypertensive therapy.

PMID- 11293943
TI  - [Hyperthyroidism and heart].
AB  - This review discusses the clinically relevant effects of thyroid hormone excess
      on the heart. Tachycardia and atrial fibrillation are usually reversible after
      euthyroidism is restored. Atrial fibrillation may, however, take several months
      to return to sinus rhythm. The increase in contractility leads to an increase of
      cardiac output. The development of a relative myocardial hypertrophy following
      long-term high-dose therapy with thyroid hormones is controversial. Cardiac
      failure at stress in spite of an increased cardiac output at rest is a phenomenon
      typical for thyrotoxicosis. Reports of dilated cardiomyopathy associated with
      Graves' disease and evidence for TSH-receptors in the human myocardium suggest a
      relationship between these two diseases. Endomyocardial biopsy studies have,
      however, failed to prove this hypothesis. Mitral valve prolapse is more frequent
      in hyperthyroid patients than in normals. Thyroid hormone excess as well as the
      autoimmune origin of the disease are suggested as etiology for this phenomenon.
      The frequently observed angina pectoris seems to be a consequence of the increase
      in consumption of oxygen in the presence of an unchanged oxygen supply rather
      than of obstruction of coronary circulation. Well documented cases of myocardial
      infarction patients with thyroid hormone excess and normal coronary arteries in
      angiography substantiate this theory. Finally diagnostic and therapeutic options
      of the two forms of thyrotoxicosis induced by the antiarrhythmic drug amiodarone
      are presented.

PMID- 11293944
TI  - [Application of a context-oriented model for the planning of psychotherapy].
AB  - Since clinical experience has shown that creating a therapeutic setting with
      borderline or psychotic patients is extremely difficult the Department of
      Psychoanalysis and Psychotherapy at Vienna University Hospital has developed a
      method of treatment designed to increase the possibilities to work with this
      group of patients. This procedure is conceptualised as "context oriented model
      exploration in psychotherapy planning" COMEPP. Initially the context is explored
      in which the psychotherapeutic model should be implemented which has so far
      failed for different reasons. Following this a setting is created in which the
      therapeutic team and the patient(s) can constructively and creatively reflect on
      alternative therapeutic models. A clinical case illustrates the problems and the
      basic structure of COMEPP in a schematic and condensed form.

PMID- 11293945
TI  - Different patterns of angioedema in patients with and without angiotensin
      converting enzyme inhibitor therapy.
AB  - BACKGROUND: There is convincing evidence for a causal relationship between
      angiotensin converting enzyme inhibitor (ACEI) therapy and angioedema, but the
      clinical features of the patients remain unclear. The aim of the study was to
      compare patterns of angioedema in patients under ACEI therapy and those without
      ACEI therapy. METHODS: One hundred and seventeen consecutive patients with
      angioedema treated in the emergency department of a 2000-bed tertiary care
      university hospital were included. A retrospective cohort study was performed,
      the exposure being ACEI therapy. The pattern of location of angioedema was the
      primary outcome measure. RESULTS: Of 117 patients with angioedema, 25 (21%)
      received ACEI therapy. In a multivariate logistic regression model, angioedema of
      the cheeks, eyelids or nose was independently negatively associated with ACEI
      therapy [adjusted odds ratio 0.13 (95% confidence interval 0.03 to 0.49), p =
      0.003]. Higher age was also significantly associated with ACEI therapy [adjusted
      odds ratio 1.85 (95% confidence interval 1.23 to 2.80), p = 0.003]. Furthermore,
      a trend towards an independent negative association between a history of
      allergies and angioedema under ACEI therapy was seen. CONCLUSION: Patients with
      angioedema under ACE inhibitor therapy differ significantly from those receiving
      no ACEI therapy in terms of patterns of angioedema and age. The applicability of
      this observation as a tool for deciding whether to continue or terminate ACEI
      therapy requires prospective evaluation.

PMID- 11293946
TI  - [Projections in the incidence of dementia in Austria for the years 1951 to 2050].
AB  - Because of the increasing life expectancy it is generally assumed that the number
      of demented individuals will steeply rise in the next decades. Dementia is a main
      reason for requiring extensive nursing care. Therefore, estimations of the future
      number of demented subjects in Austria are necessary for planning appropriate
      services. Since the age structure of the Austrian population has already changed
      during the last decades, the development of the number of demented individuals
      during the last five decades is compared with the estimations for the next five
      decades. These estimations are based on the population projections for Austria
      and on all available international meta-analyses of prevalence and incidence
      surveys. Estimations of the number of people suffering from dementia and of those
      developing dementia within one year are presented for the period between 1951 and
      2050. In 1951, the number of dementia sufferers was 35,500; by 2050 this number
      will increase to 233,800. At present, 90,500 elderly people with dementia live in
      Austria. Thus, in the next decades, the number of people suffering from dementia
      will rise more steeply than the in the past. If the projected life expectancy
      leads to a prolonged duration of illness the number of dementia sufferers will be
      markedly higher. On the other hand, the working force will decrease in the next
      decades. Therefore, while in 1951 there were 120 employable persons per demented
      person, in 2050 there will be only 17 employable persons per demented person.
      Extensive planning of the future care of demented people is an urgent necessity.

PMID- 11293947
TI  - Analysis of volatile organic compounds: possible applications in metabolic
      disorders and cancer screening.
AB  - The human breath contains a variety of endogenous volatile organic compounds
      (VOCs). The origin and pathophysiological importance of these VOCs is poorly
      investigated. Little is known about the interaction of VOCs from ambient air,
      such as those produced by plants and exhaust fumes, with the human organism. Gas
      chromatographic determination of VOC concentrations is tedious. Proton-transfer
      mass spectroscopy (PTR-MS), a new technology for the online detection of VOC
      patterns, is a valuable alternative. We present two interesting molecular
      species, isoprene and ortho (o)-toluidine, as examples of endogenously produced
      VOCs. In a case study, breath isoprene reductions during lipid-lowering therapy
      (36%) were shown to correlate with cholesterol (32%) and LDL concentrations (35%)
      in blood (p < 0.001) over a period of 15 days. Therefore, isoprene concentrations
      in human breath (measured by PTR-MS) might serve as an additional parameter to
      complement invasive tests for controlling lipid-lowering therapy. Furthermore, it
      may be a useful parameter for lipid disorder screening. Mass-108, which
      presumably represents o-toluidine in our breath samples, was found in
      significantly higher concentrations in the breath of patients with different
      tumors (1.5 +/- 0.8 ppbv) than in age-matched controls (0.24 +/- 0.1 ppbv, p <
      0.001). Inflammatory reactions do not seem to alter the pattern of mass-108.
      Therefore, it appears to be a currently underestimated carcinoma marker that
      deserves further investigation.

PMID- 11293948
TI  - [Emergency airway management-- comparison of various strategies in an unsecured
      airway].
AB  - OBJECTIVES: Gastric inflation and regurgitation of stomach contents are major
      hazards of bag-valve-mask ventilation in an emergency. The purpose of our study
      was to determine lung ventilation and gastric inflation when using the bag-valve
      face mask, laryngeal mask, and combitube with different sizes of self-inflating
      bags (max. volume: 700, 1100, 1500 ml). METHODS: Twenty-six training emergency
      doctors without prior extensive training in emergency airway management
      volunteered for our study and ventilated a bench model simulating an unintubated
      respiratory arrest patient with bag-valve-face mask, laryngeal mask, and
      combitube using paediatric, medium size, and adult self-inflating bags. Lung and
      gastric tidal volume, as well as lung and gastric peak airway pressure were
      measured with respiratory monitors and a pneumotachometer. RESULTS: When using
      either the combitube or the laryngeal mask, the paediatric vs. medium-size and
      adult self-inflating bag resulted in significantly (P < .001) lower mean +/- SEM
      lung tidal volumes (328 +/- 34 vs. 626 +/- 65 vs. 654 +/- 69 ml; and 368 +/- 30
      vs. 532 +/- 48 vs. 692 +/- 67 ml, respectively). No gastric inflation occurred
      with the combitube, while gastric inflation was comparably low when using the
      laryngeal mask with either ventilation bag (3 +/- 2 vs. 7 +/- 4 vs. 6 +/- 3 ml; P
      = NS). The paediatric vs. medium-size and adult self-inflating bag in combination
      with the bag-valve-face mask resulted in comparable lung tidal volumes (250 +/-
      23 vs. 313 +/- 24 vs. 282 +/- 38 ml; P = NS); but significantly (P < .01) lower
      gastric tidal volumes (147 +/- 23 vs. 206 +/- 24 vs. 267 +/- 23 ml). CONCLUSIONS:
      Both the laryngeal mask and the combitube proved to be valid alternatives for the
      bag-valve-face mask in our experimental model. The medium size self-inflating bag
      seems to be adequate when using either the laryngeal mask or the combitube.

PMID- 11293949
TI  - Carotid intima-media thickness in type 2 diabetes is more strongly related to
      serum apoprotein A-I in females.
AB  - BACKGROUND: Dyslipidemia in type 2 diabetes has been shown to be related to the
      incidence of macrovascular events. Increased carotid intima-media thickness is
      considered to be a marker of macrovascular disease. MAIN PURPOSE: To investigate
      a possible relationship between lipoprotein levels and carotid intima-media
      thickness as a marker of early atherosclerosis in patients with type 2 diabetes.
      METHODS: Seventy-one consecutively selected eligible patients (31 males, 40
      females) with type 2 diabetes were studied. Common carotid intima-media thickness
      was measured bilaterally by high-resolution ultrasound and the mean value from
      both sides was used for further analysis. Fasting blood samples were taken from
      each individual and their serum was analyzed for lipoprotein levels. RESULTS: In
      the entire group of patients, intima-media thickness was inversely related to
      apoprotein A-I (r = -0.33, p = 0.008) and HDL cholesterol (r = -0.23, p = 0.059)
      in univariate correlation analysis, and a positive correlation between intima
      media thickness and apoprotein B/apoprotein A-I ratio was found (r = 0.33, p =
      0.007). When genders were analyzed separately, intima-media thickness was
      significantly correlated with apoprotein A-I and apoprotein B/apoprotein A-I
      ratio in females, while no significant correlation of any lipid variable with
      intima-media thickness was observed in males. In multiple linear regression
      analysis, age (p = 0.005), male gender (p = 0.002) and apoprotein A-I (p = 0.035)
      were the only risk factors in the entire group of diabetic patients, which
      significantly predicted carotid intima-media thickness in models adjusted for
      demographic and other known risk factors. As was the case in the univariate
      analysis, no risk factor significantly predicted carotid intima-media thickness
      in males while age, apoprotein A-I and B significantly predicted intima-media
      thickness in females. CONCLUSIONS: In the present study, low serum apoprotein A
      I, a major protein component of HDL, was found to be related to increased carotid
      intima-media thickness. This relationship was stronger in females than in males,
      which suggests possible gender differences in the relationship between apoprotein
      A-1 and early atherosclerotic lesions in subjects with type 2 diabetes mellitus.

PMID- 11293950
TI  - Gastropathy and diarrhea in diabetic patients: the presence of helicobacteriosis
      and PAS-positive vascular deposits in gastric and duodenal mucosa.
AB  - AIM: To determine the presence of vascular periodic acid-Schiff's reagent (PAS)
      positive deposits in the gastric and duodenal mucosa of diabetic patients and
      controls. METHODS: Forty-six poorly controlled diabetic patients with digestive
      symptoms, aged 23 to 63 years (32 type I patients on insulin therapy with a mean
      diabetes duration of 14.2 +/- 3.1 years (mean +/- SE) and 13 type II patients
      with a mean diabetes duration of 7.2 +/- 2.3 years) were included. Of these, 17
      had mainly gastropathic symptoms while 13 had diarrhea, and the remaining 16
      patients had nonspecific symptoms. Forty control individuals of similar age and
      gender were included. Biopsy specimens were taken from areas of grossly normal
      gastric and duodenal mucosa. RESULTS: Gastric mucosa samples were pathological in
      38 of 46 diabetic patients (18 cases of chronic active H. pylori antral
      gastritis, 13 cases of chronic active H. pylori pangastritis and 7 cases of
      nonspecific chronic gastritis). Duodenal mucosa samples were pathological in
      32/46 diabetic patients. In the control group, 21 of 40 gastric samples (5 cases
      of chronic active H. pylori antral gastritis, 3 cases of chronic active H. pylori
      pangastritis and 13 cases of H. pylori-negative chronic gastritis) and 12/40
      duodenal samples were pathological. Both helicobacteriosis and gastric and
      duodenal mucosa pathologies were significantly (p < 0.01) more common in diabetic
      patients than in controls. No significant associations were found between
      histological findings of gastric mucosa and of duodenal mucosa in diabetics and
      the control group. PAS-positive material in the vascular wall of gastric (16/46
      vs. 2/40 in controls) and duodenal mucosa specimens (25/46 vs. 5/40 in controls)
      was significantly more common among diabetics (p = 0.001 for gastric and p <
      0.001 for duodenal mucosa). No significant association was found between the
      presence of gastropathy or diarrhea compared to the presence of neuropathy,
      retinopathy, nephropathy or the type of diabetes. CONCLUSION: Endoscopic
      specimens from the gastroduodenum of diabetic patients revealed a large quantity
      of PAS positive vascular deposits, probably reflecting the condition of the
      mucosal vessels in our patients.

PMID- 11293951
TI  - Enterovirus infection--a possible trigger for Graves' disease?
AB  - Viruses are potential environmental factors in autoimmune disease. Some evidence
      suggests a relationship between enteroviral infection (especially Coxsackie B
      virus) and autoimmunity. We investigated 21 individuals with recent onset of
      Graves' hyperthyroidism in regard of (subclinical) enterovirus infection.
      Thyrotoxic symptoms had started about two months before blood sample collection.
      The patients were from Upper Austria and mainly female (17/21). Their mean free
      thyroxin levels in blood were twice the maximum normal value and the majority
      achieved a euthyroid state 1 1/2 years later, after antithyroid medication. We
      employed a nested PCR reaction with primers of the enterovirus genome on blood
      samples. All were negative for RNA of the enterovirus group. Coxsackie and
      related viruses were not identified as a trigger factor in autoimmune thyrotoxic
      disease.

PMID- 11293952
TI  - Idiopathic myelofibrosis complicated by portal hypertension treated with a
      transjugular intrahepatic portosystemic shunt (TIPS).
AB  - Idiopathic myelofibrosis may be accompanied by portal hypertension. The authors
      report a 56-year-old man with idiopathic myelofibrosis and splenomegaly
      complicated by hepatopathy, severe portal hypertension and recurrent variceal
      bleeding. A transjugular intrahepatic porto-systemic shunt (TIPS) was inserted.
      Variceal bleeding never recurred. A short episode of encephalopathy, which is a
      known complication of porto-systemic shunting, ceased promptly after conservative
      treatment. The patient eventually died six months later due to metabolic
      deterioration and hepatic failure related to his underlying hematological
      disease. TIPS is a promising treatment modality for alleviating symptomatic
      portal hypertension in hematological disorders.

PMID- 11293953
TI  - [HDL-2000: A consensus. HDL--a neglected lipoprotein].

PMID- 11293954
TI  - Towards achieving civilised status for state hospitals.

PMID- 11293955
TI  - Calcium channel blockers and alpha-blockers in hypertension: what is the
      evidence?

PMID- 11293956
TI  - Death of the colon?

PMID- 11293957
TI  - James de S Wijeyeratne: a musical doctor.

PMID- 11293958
TI  - Are all brain functions computable?
AB  - BACKGROUND: Whether the human brain is nothing but an advanced computer is a
      matter of inconclusive debate. This paper contributes to that debate. METHOD:
      Critical reasoning based on evidence provided by the history of a woman who
      complained of amnesia after each of two separate acts of attempted suicide.
      FINDINGS: A life-threatening tendency (suicidal impulses) may be countered by a
      functional imperfection (selective amnesia) or a feigned malfunction
      (malingering). INTERPRETATION: Some aspects of brain function may depend on
      operations that no hitherto invented computer can duplicate.

PMID- 11293960
TI  - Chilli grinding as an opening to the study of occupational lung disease.

PMID- 11293959
TI  - Lucius A Nicholls, BA, BL, LSA, MB, B Chir, MD, CMG: father of nutritional
      science in Sri Lanka.

PMID- 11293961
TI  - The Idiot, Dostoyevsky, and epilepsy.

PMID- 11293962
TI  - Clinical features of systemic lupus erythematosus in Sri Lankan patients: results
      from a lupus clinic.
AB  - OBJECTIVES: To find the common clinical features, pattern of visceral
      involvement, treatment received and outcome in patients diagnosed as having
      systemic lupus erythematosus (SLE) on American Rheumatological Association (ARA)
      criteria. SETTING: Clinic for patients referred or admitted to the University
      Medical Unit, National Hospital of Sri Lanka, Colombo, with diagnosed or
      suspected SLE. DESIGN AND METHODS: A prospective descriptive study. Clinical
      features of patients collected at time of registration in the clinic were
      maintained in a database. Patients were followed up prospectively and changes
      recorded. Data were analysed after 3 years of follow up. RESULTS: Of the 111
      patients registered during this period, 96 (86%) were clinically diagnosed as
      having SLE. Of these, 77 patients (80%) satisfied ARA criteria for diagnosis of
      SLE. 72 were females (93%). The mean age of patients who satisfied the ARA
      criteria was 32 years (range 11 to 58), and the mean duration of disease 7 years
      (range 1 to 15). The commonest presentation was with mucocutaneous features (98%)
      and alopecia in 87%. Systemic features were found in 92% of patients. 67 (87%) of
      patients had visceral involvement with 60 (78%) having it at time of diagnosis.
      53 (69%) had renal, 42 (54%) haematological, 33 (42%) neurological, 12 (16%)
      cardiac and 8 patients pulmonary involvement. Five patients died during the 3
      year follow up and 2 developed chronic renal failure. Three patients underwent
      successful pregnancy after diagnosis of SLE. CONCLUSIONS: Our study confirmed the
      wide variability of clinical features seen in SLE. Alopecia and visceral
      involvement were common in Sri Lankan patients.

PMID- 11293963
TI  - Comparison of some clinical and histological features of colorectal carcinoma
      occurring in patients below and above 40 years.
AB  - OBJECTIVE: To determine the clinicopathological features of colorectal
      malignancies in Sri Lankan patients aged 40 years or younger, and to compare them
      with those of older patients. METHODS: The clinicopathological features of 60
      colorectal malignancies which occurred in patients aged 40 years or younger were
      compared with 245 malignant colorectal tumours in older patients. These tumours
      had been diagnosed at a University Department of Pathology over 15 years.
      RESULTS: 19.7% of colorectal malignancies occurred in patients aged 40 years or
      younger. (Male:Female ratio = 1.6:1). The mean duration from onset of symptoms to
      diagnosis was 4.2 months. There was no statistically significant difference
      between young and old patients in the presenting symptoms, site of tumour and
      Dukes' staging of colorectal malignancies. A statistically significant proportion
      of tumours in young patients was mucoid (13.3%) or signet ring cell (5%) type.
      3.3% of young patients with colorectal carcinoma gave a family history of similar
      malignancy. A history of predisposing conditions (ulcerative colitis) was present
      in 3.3% of young patients. CONCLUSIONS: The clinical presentation of colorectal
      malignancies in Sri Lankan patients below 40 years of age does not differ from
      that in older patients. Mucoid and signet ring cell carcinomas are commoner in
      the young.

PMID- 11293964
TI  - Pregnancy following renal transplantation in Sri Lanka.
AB  - OBJECTIVE: To assess the outcome and complications of pregnancy following renal
      transplantation in Sri Lanka. METHODS: Ten pregnancies following transplantation
      managed between January 1993 and July 1999 by the University Obstetrics and
      Gynaecology Unit, De Soysa Hospital for Women, Colombo were reviewed. RESULTS:
      Five women had planned pregnancy with an average duration from transplantation to
      conception of 2.3 (+/- 0.2) years; five had an unplanned pregnancy within 12
      months of transplantation. All were treated with immunosuppressives, with none
      developing rejection. In the planned pregnancy group, 3 developed pregnancy
      induced hypertension and 3 impaired glucose tolerance. All delivered mature
      healthy babies with an average birth weight of 2.6 (+/- 0.3) kg. In the unplanned
      group, 1 developed cholestatic jaundice and delivered a growth retarded baby at
      36 weeks. Another developed severe pulmonary oedema at 34 weeks (due to a past
      myocardial infarction) resulting in a fresh stillbirth. Two others has mid
      trimester foetal deaths complicating severe diabetes mellitus. The conception at
      3 months after transplantation developed diabetes mellitus and pregnancy induced
      hypertension, and delivered a live growth retarded baby. None had deterioration
      of renal function. CONCLUSION: Although a successful outcome is possible with
      stringent pre-pregnancy selection, maternal morbidity and foetal wastage can be
      high in those without.

PMID- 11293965
TI  - First isolation of Legionella pneumophila in Sri Lanka.
AB  - OBJECTIVES: To determine the presence of legionellae and species composition of
      the genus Legionella in Sri Lankan hotel cooling towers, and to determine the
      previous exposure of hotel workers to Legionella pneumophila. DESIGN: Collection
      of water samples from 16 cooling towers of air conditioning plants from 7
      representative hotels, and blood samples from hotel workers. SETTING: Department
      of Bacteriology, Medical Research Institute, Colombo 8. RESULTS: Water samples
      from 4 (57.4%) hotels selected were positive for legionellae. Five (38.4%)
      selected cooling towers yielded legionellae with viable counts ranging from 1 to
      5 colony forming units (CFU)/ml. 93.7% of the isolates were Legionella
      pneumophila. Only one hotel worker had significant antibody levels denoting past
      infection to Legionella pneumophila. CONCLUSION: Legionella does occur in the Sri
      Lankan hotel environment and Legionella pneumophila appears to be the most common
      species.

PMID- 11293966
TI  - Iodised salt and hyperthyroidism.

PMID- 11293967
TI  - Post-traumatic stress disorder after watching violent scenes on television.

PMID- 11293969
TI  - Wound infection survey at Teaching Hospital, Peradeniya.

PMID- 11293968
TI  - Pathways taken by parents of disabled children.

PMID- 11293970
TI  - Myoglobinuric acute renal failure following dengue viral infection.

PMID- 11293971
TI  - The Koro syndrome.

PMID- 11293972
TI  - Cervico-facial actinomycosis.

PMID- 11293973
TI  - Bleeding time test: why outdated methods?

PMID- 11293974
TI  - Diabolical work.

PMID- 11293975
TI  - [Usefulness of the study of myocardial viability in the clinical setting].

PMID- 11293976
TI  - [Cortical bone mass and risk factors for osteoporosis among postmenopausal women
      in our environment].
AB  - OBJECTIVE: To evaluate the relevance of the so called risk factors for
      osteoporosis among women. MATERIALS AND METHODS: A total of 150 consecutive
      postmenopausal women who had been enrolled in the gynecology outpatient clinics
      of the Health Areas affiliated to the Alcala de Henares University Hospital. Bone
      mass of these women was calculated as index of metacarpal cortical area/total
      area (CA/TA) (mm2), measured by radiogrammetry. RESULTS: With the ANOVA test, a
      late menarchial age and a shorter reproductive life induced a lower bone mass (p
      < 0.0005 and < 0.05, respectively); also, a history of bone fractures without
      previous relevant trauma (p < 0.05) was obtained. By correlational studies, there
      was a negative significance between CA/TA index and chronological age, menarchial
      age, menopausal age and number of fractures (r = -0.20 to -0.30; p < 0.05 to <
      0.0001) and a positive significance with years of reproductive life (r = 0.17; p
      < 0.05). These values virtually remain unchanged when with partial correlation
      are weight adjusted, but with the multiple regression model, the CA/TA index is
      negatively significant only with menopause years (p < 0.005). Taking the average
      of the metacarpal CA/TA index as value, a sensitivity of 50% and an specificity
      of 78% were obtained to indicate fractures and a negative predictive value of
      92%. CONCLUSION: These results indicate the greater importance of menarchial age,
      of reproductive life years and therefore of menopausal years, as determinants of
      postmenopausal bone mass and show a very acceptable specificity of the CA/TA
      index as predictive for bone fracture.

PMID- 11293977
TI  - [Guidelines for antibiotic prophylaxis of bacterial endocarditis in patients
      undergoing dental therapy].
AB  - The objective of the present work was to know the guidelines of antibiotic
      prophylaxis in bacterial endocarditis used in different spanish health centers. A
      general dental practitioner asked orally in 50 Cardiology and/or Internal
      Medicine departments throughout Spain which prophylaxis should be administered to
      a patient with a mitral valve prosthesis before a dental extraction. The results
      obtained showed that only 36 (72%) departments used the latest prophylactic
      guidelines recommended by the American Heart Association or the British Society
      for Antimicrobial Chemotherapy. Among penicillin allergic patients the antibiotic
      of choice was erythromycin (60%) followed by clindamycin (28%), although
      administered at very different dosages (11 and 3, respectively). Only in 44% of
      the surveyed departments did the guidelines for allergic and non allergic
      patients correspond to the recommended protocol by the same study group. The
      controversy generated regarding the prophylactic indications for bacterial
      endocarditis might partially account for the results obtained in this study.

PMID- 11293978
TI  - [Clinical significance of homocysteine].

PMID- 11293979
TI  - [Diagnostic management of pituitary adenomas].

PMID- 11293980
TI  - [Diagnosis of hypercoagulability].

PMID- 11293981
TI  - [Structural biopathology and planning of biomedical knowledge].

PMID- 11293982
TI  - [Abdominal pain and vomiting in an anticoagulated female patient].

PMID- 11293983
TI  - [Ophthalmologic manifestations in primary antiphospholipid syndrome].

PMID- 11293984
TI  - [46 year-old man with heart failure symptoms].

PMID- 11293985
TI  - [62 year-old man with long term evolving cutaneous lesions: diagnosis at a first
      glance].

PMID- 11293986
TI  - [Thallium-201 scintigraphy and dobutamine echocardiography in the assessment of
      myocardial viability].
AB  - BACKGROUND: The possibility of differentiating viable from non-viable tissue
      among patients with severe coronary artery disease and severe left ventricular
      impairment entails relevant clinical and therapeutic implications since it may
      influence the indication of patient revascularization. To evaluate the presence
      of myocardial viability two techniques are available in the clinical setting:
      echocardiography with intravenous infusion of dobutamine and scintigraphy with
      myocardial perfusion with thalliem-201 by means of single-photon emission
      tomography. OBJECTIVE: To compare prospectively the value of these techniques for
      detecting viable myocardium. MATERIAL AND METHODS: Thirty-five patients with
      severe coronary disease and severe left ventricular dysfunction were included in
      the study. All patients underwent an echocardiogram using incremental doses of
      dobutamine, from 5 up to 40 micrograms/kg/min in three-minute periods. For
      thallium-201 scintigraphy the rest redistribution protocol with delayed images at
      4 hours was used. The criteria for detecting viability were: a) for thallium-201,
      the presence of redistribution in delayed images and normal uptake at rest, and
      b) for dobutamine echocardiography, a sustained improvement in regional motion,
      biphasic response, and worsening. RESULTS: By considering the segmental
      improvement post-revascularization as "gold standard" of viability, the
      statistically significant variables in a logistic regression model and,
      therefore, predictors of segmental functional recovery were the biphasic response
      and the sustained response for dobutamine echocardiography and normal uptake at
      rest and redistribution in the delayed images for thallium-201. Taken together,
      the result was significant for the biphasic response of dobutamine
      echocardiography. CONCLUSIONS: The biphasic response with dobutamine
      echocardiography is the echocardiographic pattern that best predicts the
      functional recovery of the ischemic myocardium. A normal uptake and
      redistribution at four hours is the only scintigraphic pattern that can predict
      functional improvement. Of both patterns, the biphasic response is the best
      predictor of the functional recovery of the dysfunctional myocardium.

PMID- 11293987
TI  - [Acute psychosis as a manifestation of small cell carcinoma of the lung].

PMID- 11293988
TI  - [Hepatitis c infection, cryoglobulinemia and lymphoproliferative diseases].

PMID- 11293989
TI  - [HELLP syndrome: potential serious complication of preeclampsia in puerperium].

PMID- 11293990
TI  - [Pancreatitis in cocaine body-packers].

PMID- 11293991
TI  - [Enterocolitis caused by methicillin-resistant Staphylococcus aureus].

PMID- 11293992
TI  - [Adenocarcinoma of prostate in men younger than 50--rectal palpation mandatory
      with micturition problems].
AB  - In three men, aged 44, 47, and 48 years, prostatic carcinoma was diagnosed after
      a long delay, more than eight months after the onset of symptoms (obstructive and
      irritative micturition problems, erectile dysfunction, and haemospermia). The
      cancer was suspected on eventually performed rectal palpation and confirmed in
      biopsies. The serum prostate-specific antigen (PSA) levels were moderately
      increased. All were treated with goserelin and flutamide and radiotherapy on the
      emerging metastases (two patients). Two patients died, the third one, who had
      received antibiotic treatment for three months because at first prostatitis was
      suspected, was still in remission at the last follow up. Prostate cancer in young
      men is rare and may demonstrate aggressive biological behaviour. The age group
      less than 50 years of age accounts for 0.8% to 1.1% of all patients with prostate
      cancer. This form of the disease responds poorly to radiation or hormonal therapy
      and is often already too advanced for surgery. The symptoms at presentation of
      prostate cancer in young men are quite similar to those in prostate cancer
      patients beyond the fifth decade. When carcinoma grows beyond the margins of the
      prostate the prognosis is poor. In all men with micturition problems, rectal
      palpation of the prostate should be carried out as a routine.

PMID- 11293994
TI  - [Liver transplantation from a living donor: necessity or an alternative?].
AB  - Liver transplantations using a part of the liver from a living donor are already
      being performed around the world. The main arguments for performing such
      transplantations are the shortage of brain-dead donors and the consequently high
      mortality rate of patients on the waiting list for a liver transplantation. The
      disadvantages of this option are the mortality and morbidity risk for the living
      donor. The shortage of brain-dead donors could also be resolved by the
      implementation of special techniques such as split-liver and domino-liver
      transplantations or by using compromised and non-heart-beating donors.
      Furthermore, measures should be taken to reduce the shortage of brain-dead donors
      in the Netherlands. If such actions do not lead to an increase in the number of
      brain-dead donors and a willingness to restrict the indications for
      transplantation is not forthcoming then donation for liver transplantation by
      living donors is inevitable. Such a program should satisfy certain conditions and
      have the requisite medical-ethical and public support.

PMID- 11293993
TI  - [Periodontitis: a hidden chronic infection].
AB  - Periodontitis is a chronic inflammatory disease of the tooth supporting tissues
      which has a prevalence of 35% in the adult population. Risk factors are dental
      plaque, calculus, smoking, diabetes mellitus, stress and genetic traits. In
      parallel with chronic intestinal inflammatory diseases and stomach cancer, gene
      polymorphisms in the interleukin-I gene family are associated with severity of
      periodontitis. Periodontitis is usually painless. Symptoms of the disease are
      bleeding, redness and swelling of the gums, suppuration and migration of teeth.
      Halitosis may be present. Treatment of periodontitis involves supra- and
      subgingival mechanical debridement, oral hygiene instruction and surgical
      elimination of residual deepened and bleeding pockets on indication.
      Microbiological testing can be used to select patients who may benefit from
      additional systemic antimicrobial therapy. Periodontal lesions may act as a
      portal of entry for dissemination of periodontal bacteria into the blood stream,
      which may result in extraoral infections. For this reason it is recommended to
      include diagnosis of periodontitis in focal examination. Associations have been
      documented between periodontitis and cardiovascular diseases, arthritis and
      premature low birth weight infants.

PMID- 11293995
TI  - [Early diagnosis and prevention of malignant tumors in the head and neck region].
AB  - In the Netherlands more than 2000 new patients with head and neck cancer are
      diagnosed annually. Most of these cancers are squamous cell carcinomas. The use
      of tobacco and alcohol are well established aetiologic factors. Head and neck
      cancers usually affect patients above the age of 40 years and are somewhat more
      common in men than in women. The type of the initial symptoms of head and neck
      cancer depends largely on the exact location. Often, these symptoms are rather
      aspecific. However, laryngeal cancer is an exception. In this site cancer usually
      presents at an early stage with sudden hoarseness. Hoarseness of more than three
      weeks' duration requires laryngoscopic examination. Particularly the cancers of
      the floor of the mouth and the borders on the tongue can be detected early
      because of the accessibility of these sites, which allows proper inspection and
      palpation. The most common clinical manifestation of oral cancer is an indurated
      ulcer. An oral ulcer present for more than three weeks is an indication for
      biopsy. The prognosis of head and neck cancer in general depends largely on the
      stage at diagnosis. Small cancers carry a much better prognosis after surgical
      removal or radiotherapy than larger ones.

PMID- 11293996
TI  - [From gene to disease; leptin and obesity].
AB  - Homozygous mutations of the ob gene, encoding leptin, are associated with severe
      obesity, hyperphagia and insulin resistance in humans. Leptin conveys a signal
      from adipose tissue to hypothalamic nuclei that integrate whole body fuel
      metabolism, informing those nuclei about the magnitude of fuel reserves. In the
      absence of leptin, the brain perceives energy availability as insufficient and
      therefore activates powerful mechanisms to restore fuel depots. If leptin
      synthesis or signal transduction is perturbed in the presence of food, a severely
      obese phenotype ensues.

PMID- 11293997
TI  - [Diagnostic image (30). Aortic dissection type B].
AB  - An 81-year-old man with acute back pain had a dissection of the aorta abdominalis
      (type B).

PMID- 11293998
TI  - [Erectile dysfunction: prevalence and effect on the quality of life; Boxmeer
      study].
AB  - OBJECTIVE: To assess the prevalence of erectile dysfunction (ED), and its
      influence on both the quality of life, and health care seeking behaviour. METHOD:
      An age-stratified random sample was drawn from men aged 40-79 years in Boxmeer,
      the Netherlands (n = 1771), together with their partners. A questionnaire was
      mailed to the study population to collect data on ED, and the quality of life,
      both general and disorder related. The prevalence of ED was measured with the
      direct question 'Do you have problems getting an erection?'. The influence of ED
      on sexual function was measured with the Dutch version of the Sexual Function
      Inventory questionnaire. RESULTS: Seventy percent of all men (n = 1233) and 73%
      of their partners (n = 1071) responded to the questionnaire. The prevalence of ED
      increased with age class. To the question regarding problems to get an erection,
      13% (95% confidence interval: 11-15%) of all men answered affirmatively (40-49
      years: 6%; 50-59: 9%; 60-69: 22%; 70-79: 38%). All men aged 40-49 years of age
      with ED and 16% of men aged 70-79 with ED considered their ED as bothersome.
      Amongst 40 to 49 year old men with ED, 64% considered their ED as a big or rather
      a big problem. Amongst older men this percentage was much smaller: 50-59 years:
      38%; 60-69: 37%, and 70-79: 27%. Thirty-four percent of all men with ED and 16%
      of their spouses were dissatisfied with their sex life. Twenty-five percent of
      men with ED consulted a doctor, with a mean delay of 13 months. ED bore a strong
      correlation with the general quality of life and comorbidity. CONCLUSION: ED was
      a common disorder within the population. Its prevalence was higher among older
      age groups, but they regarded ED as less of a problem than the younger age
      groups. Only a quarter of all men with ED consulted a physician.

PMID- 11293999
TI  - ['Leiden Impotence Screening Test'(LIST) in men with erectile dysfunction as a
      pre-selective method prior to psychophysiological diagnostic tests].
AB  - OBJECTIVE: To compare, in men with erectile dysfunction, the diagnosis obtained
      with the 'Leiden impotence questionnaire' (LIQ)--which differentiates between
      psychogenic and organic erectile dysfunction--with the clinical diagnosis based
      on psychophysiological diagnostic screening (PDS). DESIGN: Exploratory,
      comparative, and prospective. METHOD: The LIQ-questionnaire was administered to
      320 consecutive patients with erectile dysfunction who underwent PDS (i.e. visual
      sexual stimulation and penile vibration) in the Department of Endocrinology and
      Reproduction, Erasmus University Medical Centre, Rotterdam, the Netherlands. The
      clinical diagnosis was based on PDS and later, retrospectively, compared to the
      LIQ-based diagnosis (only the first six of the 11 LIQ-questions were answered by
      all patients). RESULTS: The clinical diagnosis, psychogenic or somatic,
      corresponded well with the LIQ-diagnosis. Following PDS an organic aetiology was
      assumed in 30% of the patients; compared to 33% according to the LIQ. For a
      psychogenic aetiology the figures were 70% and 67% respectively. Overall there
      was a 74% correspondence between PDS-diagnosis and the LIQ-diagnosis. Age was a
      significant factor: younger men (< 40 years) had the highest LIQ-score (compared
      to men aged 40-60 and > 60 years) and the strongest penile responses. This is
      indicative of a more frequent psychogenic aetiology of the erectile dysfunction
      in younger men. CONCLUSION: Elaborate psychophysiological diagnostic screening is
      not necessarily the first diagnostic choice in men with erectile dysfunction; one
      may start by applying the LIQ. A high LIQ-score (5-7) virtually excludes a
      somatic aetiology. A low LIQ-score (0-2) necessitates further psychosomatic
      diagnostic screening, preferably with PDS.

PMID- 11294000
TI  - [Neostigmine treatment of acute pseudo-obstruction of colon (Ogilvie syndrome)].
AB  - In a 77-year-old male patient with Parkinson's disease and with acute pseudo
      obstruction of the colon (Ogilvie's syndrome) conservative therapy was
      ineffective. Neostigmine was recently shown to be effective and safe for the
      treatment of Ogilvie's syndrome. Intravenous neostigmine treatment caused a
      prompt clinical and radiological response in the patient. Early recognition of
      the condition and prompt neostigmine treatment if conservative measures fail is
      important to reduce the risk of bowel perforation.

PMID- 11294001
TI  - [Do we understand Brussels? Risks and opportunities for the Netherlands' health
      care policy within the European Union].
AB  - Until recently, the European Union (EU) health agenda was limited to a selection
      of public health issues and good intentions of the Ministers of Health of the EU
      Member States. Lack of political will on the part of Member States to develop
      common policies in the fields of health care and social security is increasingly
      being bypassed by the political will and power of the European Parliament to
      initiate common action in these fields such as the Rocard report, for example,
      concerning the financing of health care. Furthermore, EU common market and other
      financial-economic regulations and policies already substantially affect the
      functioning of health care systems in Member States. The Netherlands' trade and
      professional associations should develop their organisation-specific EU
      strategies and policies as EU institutes, rules and culture substantially differ
      from national political and governmental systems; in recent years, the Dutch
      government has not always been successful in its approach and operations within
      the EU arena.

PMID- 11294002
TI  - [Roaming through methodology. XXIX. P].

PMID- 11294003
TI  - [Roaming through methodology. XXIX. P].

PMID- 11294004
TI  - [Prevalence of lower urinary tract symptoms in men and their influence on their
      quality of life: Boxmeer study].

PMID- 11294005
TI  - Investigation into the effects of amyloid (1-42) beta-peptide upon basal and
      antigen-stimulated hexosaminidase and serotonin release from rat RBL-2H3
      basophilic leukemia cells.
AB  - There is evidence that beta-amyloid (A beta) peptide infusion in vivo produces a
      degranulation of vascular mast cells. It would be useful to investigate the
      interaction between A beta and mast cells in a simple in vitro model system in
      order to determine the cellular mechanism by which exposure to A beta peptides
      results in mast cell degranulation. In the present study, the effect of A beta(1
      42) upon the release of granular hexosaminidase and serotonin has been
      investigated using the cognate rat mast cell line, RBL-2H3. Sensitization of
      these cells for 1 h with anti-DNP IgE (monoclonal anti-dinitrophenyl) results in
      a large release of hexosaminidase and serotonin due to degranulation when the
      cells are exposed to DNP-HSA (albumin, human dinitrophenyl). Pretreatment
      overnight with A beta(1-42) (10 and 30 microM) did not affect either the basal or
      antigen-stimulated release of hexosaminidase or serotonin. A similar lack of
      effect of A beta(25-35) and the lipid peroxidation product HNE upon antigen
      stimulated release of hexosaminidase or serotonin was also found. It is concluded
      that RBL-2H3 cells are not a useful model for mechanistic studies into the
      effects of beta-amyloid peptides upon vascular mast cells.

PMID- 11294006
TI  - Induction of metallothionein mRNA expression in the mouse liver after cadmium
      injection as measured by the reverse transcriptase-polymerase chain reaction
      method.
AB  - Metallothioneins (MTs) are low molecular weight proteins that have been
      considered to be important metal-binding proteins in the defense against cadmium
      (Cd) toxicity in animals. These proteins are known to be induced by the injection
      of heavy metals such as Cd. Previously, we developed the RT-PCR method to measure
      the level of MT mRNA expression. In this study, we analyzed the time course and
      dose response of Cd-induced MT-I mRNA expression in the male and female mouse
      liver. By this method, we measured hepatic MT-I mRNA expression which reached the
      highest peak 6 h after subcutaneous injection of 1.1 mg/kg Cd in 9-week old male
      and female mice compared with those of corresponding controls (0 h). There was no
      statistical difference in the hepatic MT-I mRNA expression between male and
      female mice 6 h after the injection of this dosage. However, it is notable that
      the MT-I mRNA expression in male mice was much higher than that in females 6 h
      after injection of 0.5 mg/kg Cd. Thus, the induction of hepatic MT-I mRNA
      expression is dependent on the sex of the mouse, the dosage and the time course
      of Cd.

PMID- 11294007
TI  - Relationship between antidepressants and glycolipids in the forced swimming test
      in mice.
AB  - GalNAc alpha 1-3GalNAc-lipids induce an antidepressive-like effect in mice in the
      forced swimming test. In the present study, the relationship between the effects
      of several antidepressants and serum glycolipid reactivities were investigated.
      The antidepressants imipramine, maprotiline, paroxetine, trazodone and mianserin
      induced an effect in forced swimming in mice after 1 or 6 h but not 15 min after
      treatment. The GalNAc alpha 1-3GalNAc-lipid globopentaosylceramide dose
      dependently induced the effect only 15 min after treatment, and the glycolipid
      reactivities were found in the serum dose-dependently at the period that the mice
      showed the antidepressive-like climbing behavior. The results strongly suggest
      that glycolipid production, and not the central neurological activities of the
      antidepressants, induce the antidepressive effect in mice.

PMID- 11294008
TI  - Topical amiloride solution accelerates healing of mechanical skin ulcers in
      albino rats.
AB  - The present investigation was undertaken to explore the ulcer healing properties
      of three dosage schedules of various concentrations of topically administered
      amiloride solution in mechanically produced skin ulcers in albino rats. Four skin
      ulcers (two on either side of the midline) were made 2.5 cm apart on the
      preshaved back of each anesthetized rat with a round body skin biopsy punch (7 mm
      diameter) through the dermis to the depth of subcutaneous tissue. The animals
      were randomly divided into groups of 5 rats each. Ulcers on one side of the
      midline were treated with normal saline and served as control, whereas those on
      the other side were treated with amiloride solutions. Each ulcer was observed for
      its size, slough formation and any sign of irritation on alternate days until
      healing was complete. Healing of ulcers was significantly accelerated with all
      the strengths of amiloride (0.01, 0.02 and 0.04%) in all the dosage schedules
      (o.d., b.i.d. and q.i.d.) in terms of days required for complete healing, ulcer
      size and area under the size-time curve. This acceleration was dose-dependent
      with maximum effect at b.i.d. administration of 0.04% solution. No irritation or
      suppression of immunity was noticeable. Thus topical amiloride may prove to be an
      inexpensive and better ulcer healing agent with no apparent side effects.
      Inhibition of u-PA by amiloride seems to be responsible for this effect.

PMID- 11294009
TI  - Effect of He-Ne laser treatment on the level of lipid peroxidation products in
      experimental cataract of rabbit eyes.
AB  - The effect of low-intensity laser irradiation on the processes of lipid
      peroxidation in lens homogenate and aqueous humor during experimental diquat
      induced cataract of rabbit eyes was studied. The levels of primary and secondary
      products of lipid peroxidation (LPO), conjugated dienes and thiobarbituric acid
      reactive substances (TBARS), were evaluated. We found that the experimental
      cataract model leads to a significant increase in the content of conjugated
      dienes and in the content of TBARS both in lens homogenate and in aqueous humor.
      The data obtained support the important role of oxidative stress in the
      development of the diquat-induced cataract model. Low-intensity laser treatment
      does not provoke a significant decrease in conjugated dienes or in TBARS in
      either lens homogenate or aqueous humor. Although our therapeutic scheme led to a
      slightly decreased level of LPO products, we conclude that the effect of low
      intensity laser-irradiation may depend on the dose applied, individual tissues
      and other factors.

PMID- 11294010
TI  - Placental transfer of the antioxidant stobadine at different gestational stages
      in rabbits.
AB  - The distribution of [3H]-stobadine, a pyridoindole antioxidant, was investigated
      in New Zealand white rabbits and their fetuses on days 20 and 27 of gestation.
      The concentrations of [3H]-stobadine were determined in maternal and fetal organs
      after oral administration in a single dose of 5.0 mg/kg. The results of the study
      showed that during the late period of gestation the fetal organs, especially the
      brain and heart, were under the protective action of the antioxidant stobadine.

PMID- 11294011
TI  - Bioequivalence of rifampicin when administered as a fixed-dose combined
      formulation of four drugs versus separate formulations.
AB  - A bioequivalence study of the antitubercular drug rifampicin in a four-drug
      combination (rifampicin, isoniazid, pyrazinamide and ethambutol) and separate
      formulations of the drugs at the same dose levels was carried out in a group of
      22 healthy male volunteers. The investigation was designed as an open crossover
      study. The drugs were administered once in individual formulations and once in a
      fixed-dose combination. The WHO-approved protocol was followed according to which
      six blood samples were collected over a period of 8 h for each volunteer and each
      experimental session. Pooled urine samples were also collected during the study.
      Rifampicin and desacetyl rifampicin concentrations in both plasma and urine
      samples were assessed. Various pharmacokinetic parameters such as AUC0-8 h, Cmax
      and Tmax were calculated for both rifampicin and desacetyl rifampicin. The
      results indicated that combined (the four-drug combination) and separate
      formulations are bioequivalent for rifampicin.

PMID- 11294012
TI  - Isolation, sequence and genotyping of the drug metabolizer CYP2D6 gene in the
      Colombian population.
AB  - Cytochrome P450 2D6 monooxygenase metabolizes several commonly used drugs,
      particularly psychotropics and cardiovascular agents. The gene that encodes this
      isoenzyme is highly polymorphic, with 1-10% of the population carrying mutations
      that produce an inactive enzyme, and 1-29% of individuals who possess additional
      copies of functional CYP2D6 genes. The genotypic features of the CYP2D6 gene have
      already been studied in many ethnic groups; however, the genetic characteristics
      of this enzyme are unknown in the Colombian population. The allelic variants and
      mutations of this polymorphic isoenzyme are the main cause of interindividual and
      interethnic differences in the therapeutic efficacy and adverse effects at
      standard doses of drugs metabolized by the products of the CYP2D6 gene. In the
      present study we have isolated, sequenced and genotyped the CYP2D6 gene in the
      Colombian population. The distribution of allelic frequencies of 10 alleles
      associated with normal, diminished or increased CYP2D6 activity has been studied
      in 121 healthy volunteers. The commonest alleles detected in the Colombian people
      were the functional alleles *1 (38.8%) and *2 (37%). Among the seven
      nonfunctional alleles studied in our sample, we found frequencies of 19.4%, 1.6%,
      1.2% and 0.8%, for the *4, *17, *3 and *5 alleles, respectively. The alleles *6,
      *7 and *8 could not be identified in any of the subjects studied. The frequency
      of the duplicate allele was 1.2%. In this Colombian sample, 91.7% of the
      individuals were normal metabolizers (EM), 6.6% were poor metabolizers (PM), and
      1.7% were ultrarapid metabolizers (UM). These results show that the allelic
      distribution of the CYP2D6 gene in the Colombian population of mestizo-prevalent
      subjects is compatible with the genomic assembly of the constitutive tri-ethnic
      origin of this Latin American country.

PMID- 11294013
TI  - [Giant-cell reaction in the breast after fine-needle aspiration].
AB  - We report two cases in which fine needle aspiration (FNA) in the breast generated
      changes histologically mimicking malignant lesions. In both cases a population of
      giant cells was present; the cells were osteoclast-like in the first case and
      'atypical' multinucleated stromal giant cells in the second. The underlying
      lesion was pseudoangiomatous stromal hyperplasia (PASH) in both cases. The
      reactive nature was confirmed by retracing the needle tract and by the uneventful
      follow-up of 7 or 2 years, respectively. We propose that giant cell reaction be
      included in the list of FNA-generated changes.

PMID- 11294014
TI  - [The hematopoietic stem cell: biology and clinical applications].
AB  - The hematopoietic stem cells (HSCs) are defined as cells that are able of both
      self-renewal and multilineage reconstitution of the hematopoietic system. Their
      biological properties and, similarly, the gene regulation, the positive and
      negative factors of the hematopoietic progenitor cells and the models of the
      hematopoietic amplification in the murine system are described. The clinical
      relevance of HCS has been obtained by the characterization and function of the
      CD34 cell surface molecule. The methods of isolation, selection and purification
      of HCS, the clinical use (particularly the mobilization of peripheral CD34+
      cells) are detailed. Finally the potential advantages and use of HCS in vivo
      expansion are described.

PMID- 11294015
TI  - [The STF Project: Female Tumor Screening].
AB  - A pilot study has been carried out to evaluate women's compliance to a screening
      program for cervical cancer. The study, initiated in 1994, was performed in
      conjunction with the ACRO project of the CNR by the Italian National Health
      Institute, in collaboration with La Sapienza University of Rome and the National
      Institute for Cancer Research in Genoa. A preliminary telephone survey was
      carried out on a sample of 400 women (200 in Rome and 200 in Genoa) to assess,
      among other factors, their attitude towards the screening program. Afterwards, an
      ad hoc advertising campaign was launched and 21,827 women, randomly chosen from
      the register office's lists, were sent a personal invitation to participate in
      the screening. Most women showed interest in attending the screening program at
      the interview, but the percentages of participation were low (25.7% in Genoa and
      27.3% in Rome). On the other hand, a high percentage of women who participated in
      the screening had already had a Pap test in the previous three years (Genoa, 73%;
      Rome, 76%). The recruiting techniques that were used in this study, and that are
      commonly used, do not seem to reach the core of the target population for
      cervical screening, i.e. women who have never had a Pap test or who had a Pap
      test more than 5 years earlier. New methods of recruiting aimed at categories at
      risk and based more on direct contacts need to be developed.

PMID- 11294017
TI  - [Telemetric intraoperative diagnosis among hospitals in Trentino: first
      evaluations and optimization of the procedure].
AB  - Telemetric, intraoperative frozen section diagnosis may be a useful tool for
      rural hospitals lacking an in-house pathology service. As a part of a Health
      Ministry Project on Telemedicine in Trentino (northern Italy), we developed a
      static telemicroscopy system (STeMiSy). This system connects the rural hospital
      of Cles with the main hospital of Trento. The two hospitals are 40 kilometers
      apart, and the road connecting the two towns runs across the mountains and has a
      heavy traffic. Before putting STeMiSy into practice, we tested the software and
      hardware on the LAN of the regional hospital system, by connecting the pathology
      services of Trento and Rovereto (20 kilometers apart). This test phase lasted
      three months and has not revealed major problems in the LAN nor in the robotic
      microscope, which was always precise and reliable. The quality of the images and
      the speed of transmission were largely sufficient for intraoperative frozen
      section diagnosis. Minor details of the histological slides were not always
      appreciated on the panoramic view. This loss of some details may be due to the
      quality of the panoramic view, which represents the 'surfing map' to read the
      cases. Nevertheless, the recognition of these small details was not so relevant
      as to change the surgical approaches. An audioconference system, utilizing the
      same transmission channel, not only slightly slowed the transmission but also
      caused some instability to the system. The audioconference system has therefore
      been abandoned, and when necessary we used the normal telephone. Macroscopic
      images of the whole surgical specimen, the surgeon's responsibility for the
      sampling, good technical quality of the slide, and good training will allow us to
      perform remote frozen section diagnosis in the absence of the pathologist. We
      believe that the main, and probably only, difficulty for this approach is not of
      a technical nature, but reflects the pathologist's resistance to making a remote
      video diagnosis.

PMID- 11294016
TI  - [The European aptitude test for cervical cytopathology].
AB  - The EFCS/QUATE aptitude test is an important measure for evaluating quality in
      cervical cytopathology and for assessing the level of experience and competence
      in cervical cancer screening. The test, set up in the 1990s by the ECTP/CCS
      working party, has been performed since 1992 in several European countries:
      United Kingdom, The Netherlands, Germany, Denmark, Portugal, Slovenia, Hungary
      and Italy. In Italy, the test has been performed at the Istituto Superiore di
      Sanita in 1992 and 1993 and in some Italian universities (Padua 1993, Turin 1994,
      Sassari 1995, Naples 1996, Messina 1998) and in one hospital (Genoa 1997). The
      minimum passing score is 60/100 (60% in all sections). The aptitude test for
      cytotechnologists includes: a written test (50 multiple choice questions); a
      practical test (screening 10 unmarked cervical smears; spot test of 20 slides
      with a fixed field of view); and an oral test, for borderline candidates when
      necessary (60%) or for the diploma with 'distinction' (95%). Successful
      candidates receive the Certificate of Aptitude in Gynecological Cytotechnology
      and are entitled to use the initials CT (EFCS-GYN) after their names for
      professional purposes. The aptitude test for anatomopathologists includes an oral
      test and a practical test (screening 5 unmarked cervical smears, spot test of 20
      slides with a fixed field of view, and reading and diagnosing 3 complex cases).
      Successful candidates receive the certificate of gynecological cytopathology. The
      first aptitude test for anatomopathologists in Italy, organized and endorsed by
      the Istituto Superiore di Sanita in collaboration with SIAPEC (Italian Society of
      Pathological Anatomy and Cytopathology) and in agreement with the European
      guidelines for cervical cancer screening, was performed on 18 December 1997 in
      Rome. The total number of aptitude tests carried out in Europe is 15 for
      cytotechnologists and 4 for anatomopathologists. A total of 317 cytotechnologists
      and 73 anatomopathologists has taken the test; the success rates are 77% and 70%,
      respectively.

PMID- 11294018
TI  - [An autopsy case of neonatal lactic acidosis].
AB  - Defects in mitochondrial enzymes, such as pyruvate dehydrogenase and cytochrome
      oxidase, cause hereditary disorders which lead to modifications in cellular pH
      due to the accumulation of pyruvate and lactic acid. Mitochondrial diseases
      include severe neonatal diseases and less severe forms of adult diseases. We
      report the case of lactic acidosis in a newborn girl who was delivered at 36
      weeks of gestation and who died 3 months after birth. Her family history revealed
      a relative with tetraparesis and mental retardation. Her clinical findings, such
      as tonic-clonic convulsions and accumulation of pyruvate and lactic acid in
      blood, urine and cerebrospinal fluid, were refractory to treatment and developed
      soon after birth. Ultrasound scans of the brain some days before death revealed
      cerebral atrophy with ventricular dilatation and thinning of the corpus callosum
      and septum pellucidum. The clinical diagnosis of metabolic lactic acidosis was
      confirmed by macroscopic, microscopic and ultrastructural findings seen at
      autopsy. On macroscopic examination, the heart was hypertrophic, and the brain
      was atrophic with ventricular dilatation and thinning of corpus callosum. Small
      cystic lesions were present in the basal ganglia. On microscopic examination, the
      latter were characterized by loss of neurons, gliosis and capillary
      proliferation. Ultrastructural examination of the heart and skeletal muscle
      showed lysis of myofibrils, mitochondrial pleomorphism and hyperplasia, and
      crystalline inclusion in mitochondria and in the matrix compartment. In reporting
      this case, we emphasize the importance of accurate postmortem examination and
      clinical data for the diagnosis of metabolic lactic acidosis.

PMID- 11294019
TI  - [Extrarenal retroperitoneal angiomyolipoma: description of a case and review of
      the literature].
AB  - A case of retroperitoneal extrarenal angiomyolipoma is described. The patient, a
      61-year-old woman, presented with a large retroperitoneal lipomatous mass.
      Histologically, it consisted of lipomatous tissue. Focally, there was
      interstitial and perivascular proliferation of bland oval and epithelioid cells
      with a large, eosinophilic or clear cytoplasm. Immunohistochemically, these
      elements were positive for smooth muscle actin and HMB-45. The literature on
      retroperitoneal extrarenal angiomyolipoma is briefly reviewed. It is important
      that the pathologist recognize this lesion, even when it is located in the
      retroperitoneum outside the kidney, and differentiate it from a liposarcoma.

PMID- 11294020
TI  - [Benign unclassified tumor of the gonadal stroma: importance of alpha-inhibin
      expression].
AB  - We present a begin unclassified gonadal stroma tumor in a 62 year-old menopausal
      woman. We discuss the differential diagnosis with the most frequent fibromas and
      thecomas and with the rarer sclerosing stromal tumor of the ovary. The
      immunohistochemical staining for alpha-inhibin was important to confirm the
      origin of the spindle-cell proliferation from undifferentiated (unclassified)
      ovarian gonadal stroma.

PMID- 11294021
TI  - [Mixed neuroglial tumor: description of a case].
AB  - A case of neuroglial tumor in a 18-year-old man is presented. The neoplasm was
      composed by two cell types. One type showed features typical of neuronal cells,
      while the other resembled glial cells. The diagnosis was confirmed by
      immunohistochemistry results.

PMID- 11294022
TI  - [Stomach lymphomas: minimum diagnostic requirements for gastrointestinal
      histopathological diagnosis].
AB  - Gastric lymphomas have been the subject of intensive studies in the last years
      and important progress has been made regarding their etiopathogenesis and
      therapy. Diagnosis of gastric lymphoma is usually made on bioptic material taken
      at endoscopy. Histopathologic diagnosis is frequently difficult. This paper
      summarizes the main diagnostic criteria of this setting. It analyses the
      morphological, immunohistochemical and molecular features to be considered for
      the differential diagnosis between: reactive process vs low grade B-cell gastric
      MALT lymphoma, B-cell MALT lymphoma vs other low grade lymphomas involving the
      stomach and low grade vs high grade gastric lymphoma. The histopathological
      aspects of gastric biopsies after antibiotic treatment for Helicobacter pylori
      eradication and the role of molecular analysis in the follow-up of these patients
      are also considered.

PMID- 11294023
TI  - [Goethian reflections on the problems of contemporary science].

PMID- 11294024
TI  - [Virus disk diseases, worms, and... Trojan horses].

PMID- 11294026
TI  - [About autopsy].

PMID- 11294027
TI  - [What is the Italian Society of Gynecopathology?].

PMID- 11294028
TI  - [Science and technology for the new millenium].
AB  - The arrival of the new millennium move us to make a series of reflections about
      the status of Science and Technology in Venezuela and consequently, in Latin
      America. It seems that we have not understood yet, that having strong Science and
      Technology put us in a more advantageous position to cope with the problems
      related to our underdevelopment. Decisive and expeditious actions are required in
      Venezuela and Latin America to reduce the scientific and technological gap
      between developed and underdeveloped countries. These actions can be portrayed in
      two possible scenarios. The first one, dealing with scientific funding of basic
      and applied research focused on areas of critical need. Central, regional and
      local governments must share responsibilities for scientific development and
      hence, to provide appropriate funding for scientific research. The financing of
      personnel and the acquisition of equipment and materials for qualified scientists
      and research centers should be guaranteed. The second scenario deals with
      universities and superior education institutions which should match their
      curricula to contemporaneous knowledge, and to assume their role as science
      promoters through a creditable scientific leadership. Also, they must provide
      affordable opportunities for teachers and scientists to catch up with the
      continuing and progressive advance of science, through the establishment of inter
      institutional agreements in Venezuela and abroad which would allow Venezuelan
      scientists to participate in joint research ventures, and therefore, to be in
      touch with knowledge and technologies not available in our countries.

PMID- 11294029
TI  - [Nutritional and metabolic factors as risk factors for cardiovascular diseases in
      an adult population in the city of Maracibo, Estado Zulia, Venezuela].
AB  - To analyze the nutritional and metabolic risk factors for Cardiovascular Diseases
      (CVD) present in a group of people in the city of Maracaibo a study was performed
      with 209 volunteers (145 women and 64 men) between 20 and 89 years of age who
      underwent: a) Anthropometric Evaluation: Body Mass Index (BMI) and Waist-to-Hip
      Ratio (WHR) and Physical Examination: Systolic (SBP) and Diastolic Blood Pressure
      (DBP); b) Dietetic Evaluation (24 hours recall), and c) Biochemical Evaluation:
      Glycemia (GLYC), Triglycerides (TG), Total Cholesterol (CHOL), HDL-C, LDL-C and
      VLDL-C, applying enzymatic methods. It was also investigated, their Age, Family
      History of Metabolic Alterations (FHMA), physical activity, smoking habits and
      alcohol consumption. More than 50% of the individuals showed a BMI > 25; 64% of
      women showed a WHR value > 0.8; 34 and 28% of men and women respectively had a
      high fat ingestion (HFI); 36% of men had hypertriglyceridemia and high levels of
      VLDL-C; 41% of women and 30% of men showed decreased HDL-C. A high frequency of
      FHMA was found in 85% of women and 78% of men followed by sedentary life in 64%
      of men and 79% of women. The age significantly (p < 0.05) affected the values for
      WHR, SBP, DBP, GLYC, CHOL, TG, HDL-C, LDL-C and VLDL-C. The dietetic evaluation
      showed a diet that was low in calories, high in protein, normal in fat and low in
      carbohydrates. It is concluded that the population elected for this study might
      be considered under a high risk for CVD, since both nutritional and metabolic
      factors, as well as the other risk factors analyzed, were present in a high
      percentage of the individuals studied.

PMID- 11294030
TI  - [Trisomy 21. Report of 2 cases with unusual karyotypes].
AB  - We report two patients with trisomy 21 whose karyotypes revealed unusual
      translocations. In the first case there was a tandem translocation with two
      chromosomes 21 attached to the long arm of chromosome 10 (45,XX + tan(10:21;21).
      In the second case there was an inverted tandem translocation between two
      chromosomes 21 attached through their long arms (46,XY + dic(21q:21q). The
      clinical picture in both patients was not different from the usually found in
      trisomy 21. Since the parent's karyotypes were normal in both cases, it is
      assumed that both translocations arose "de novo". The need for karyotyping all
      cases of Down syndrome is emphasized.

PMID- 11294031
TI  - [Effect of intralesional treatment with emetine hydrochloride on Leishmania
      (Viannia) braziliensis in hamsters].
AB  - The therapeutic effect of the emetine hydrochloride alkaloid administered
      intralesionally was compared with that of standard parenteral treatment with
      Glucantime in outbred male hamsters experimentally infected with 4 x 10(3)
      amastigotes of Leishmania (Viannia) braziliensis. Both chemotherapeutic agents
      reduced significantly (P < 0.01) the average lesion sizes in experimental animals
      in comparison with those untreated. The alkaloid infiltration was found to be as
      effective as the antimonial injection for clinical resolution. The
      ultrastructural effects on the Leishmania parasites exposed to emetine were
      observed mainly in the inner cytoplasm, which appeared disorganized, pycnotic and
      with loss of morphological definition; however, any known emetine hydrochloride
      action mechanism factor could not be directly related with ultrastructure effects
      detected on leishmanial parasites. Smears, conventional histopathology, culture
      in NNN medium and indirect immunoperoxidase method showed viable amastigotes in
      nodules and/or scars of all the evaluated hamsters 75 to 230 days after the end
      of treatment. These findings suggest that measurement of the size of cutaneous
      leishmania lesions does not appear to be a valid criterion for evaluating the
      efficiency of chemotherapy in experimental LT. Detection of leishmania parasites
      in the lesion scars, supports the hypothesis that man could be considered as an
      domestic reservoir.

PMID- 11294032
TI  - [Polycystic ovary syndrome of extra-ovarian origin. Review].
AB  - An established fact in the polycystic ovarian syndrome (POS) is an abnormal
      ovarian steroidogenesis. Though this suggest an intrinsic ovarian defect, the
      syndrome could also be influenced by factors outside the ovaries. Although of
      unknown etiology, the POS is one of the most frequent endocrine disorders in the
      gynecologic practice. The disorder is characterized by ultrasound findings of
      enlarged polycystic ovaries, hyperandrogenism, menstrual disorders, obesity and
      including the appearance of infertility. There are a series of mechanisms
      involved in the extraovarian androgen increase in patients with POS. Among these
      mechanisms are implicated those of central and peripheral origin, genetic factors
      and adrenocortical dysfunction. In the same way, the alterations produced could
      imply genetic, molecular biological, biochemical, physiological and
      endocrinological factors. Sometimes all these factors could interact at the same
      time. The high serum androgen level could stop the pituitary gonadotropin
      production, either as a direct mechanism or as a result of its peripheral
      conversion. The increased androgens also explain the manifestations of clinical
      acne, hirsutism, and the detention in follicular ovarian maturation. All these
      manifestations are related with the menstrual disorders, anovulation, and
      infertility that these patients develop. The characteristics of the extraovarian
      POS include the 17-hydroxyprogesterone elevation in response to the ACTH test and
      the dexamethasone suppression of adrenal androgens. It is possible to improve the
      ovarian function in some patients with POS. This could be achieved with
      clomiphene citrate associated with glucocorticoids to induce ovulation.

PMID- 11294033
TI  - [Managing adolescent and adult victims of extra-familial rape soon after
      aggression].
AB  - Rape victims often experience severe and prolonged symptoms in the aftermath of
      the assault. Psychological assistance offered rapidly after the assault should
      mitigate the intensity and moderate the duration of rape-related problems. This
      paper tried to identify the widely-accepted therapeutic approaches from a review
      of the current literature; it has its roots in the clinical experience acquired
      by our mobile crisis service in this type of situation, too. The goal of the
      following practices concerning the victim and the victim's immediate family is to
      assist the victim to reclaim control as quickly as possible over what has
      happened and to return to a normal functioning. The therapist should adopt an
      empathetic attitude, actively and instructively, even more so, and in an even
      more flexible way than for other patients. Knowledge of one's potential reactions
      to that kind of situation is useful since the counter-transference is here
      particularly intense. Doubting the patient's word is part of these negative
      reactions and must be avoided. It is better to respect the victim's feelings of
      guilt in the first instance. The relating of the facts, despite its cathartic
      value, should not be imposed on the patient. It should be noted that these last
      two points are controversial. It is also important to give information, during
      interviews, about the symptoms which can occur, the defence mechanisms that the
      individual sets up for just such occasions and on the most common difficulties
      encountered in personal relationships. In particular, the therapist must verify
      that concrete measures are taken to protect the victim against another attack. As
      far as the immediate family is concerned, it seems particularly important to
      involve them and, better still, meet them. Their reaction to the rape has a
      determining influence on the victim's capacity to cope with the trauma and its
      consequences. On the one hand, the immediate family should be helped in giving
      support to the victim by telling them all the details of what the patient could
      suffer, their potential reaction towards the victim and the victim's potential
      reactions towards them. The question of security must also be brought up with the
      family, in particular the risk of suicide which can be great. On the other hand,
      it is important to meet the family to give them support because they too may have
      difficulty in coming to terms with the violence of the aggression and its
      consequences. These approaches are up to now the only guidelines available since
      no psychotherapeutic technique (based on controlled studies) has proved to be
      more efficient than another and since the clinical experience of the authors are
      leading them to opposite therapeutic options. Different psychotherapeutic
      techniques are recommended: short therapies such as cognitive-behavioural
      therapies or hypnosis, or longer ones such as psychoanalytic psychotherapy.
      Several of these different options, to which must be added physical techniques
      like relaxation and medication, are often used simultaneously and/or in
      succession. As for drug treatments no controlled study conducted with this
      population has proved their efficiency on post-traumatic stress disorder.
      According to us they are essentially useful in order to diminish the intensity of
      the symptoms of anxiety.

PMID- 11294034
TI  - [Alexithymia and psychological trauma--analysis of verbal expression of subject
      with post-traumatic stress disorder: an exploratory study].
AB  - The aim of this preliminary study is the analysis of the utterances of subjects
      suffering from Post-traumatic disorder. The study is based on the recent methods
      of discourse analysis developed in France by Ghiglione and Blanchet (1991, 1998).
      We have tried to know how victims of psychical trauma verbalize their different
      emotional reaction to the traumatic event. We expected to find discursive
      indicators characteristics of alexithymia when they speak about their emotion
      associated to traumatic event, that is to say an inhibition of the verbal
      expression of emotion, a factual, descriptive and objective discourse, a
      diminution of the personal engagement, difficulties to give explanations about
      the violent trauma. This study shows that the victims of psychical trauma don't
      present a lack of verbalization of their emotions but a dissociation in the
      expression of their emotions. The emotional words are more frequently associated
      to the symptoms than to the traumatic event that had been at the origin of the
      symptoms. This dissociation is similar to a particularity of alexithymia as it
      was described by Sifneos (1996). The study also shows that the distribution of
      the discursive indicators in the different themes discussed by the subjects
      constitutes an interesting way of work needing then the application of
      experimental and comparative methods.

PMID- 11294035
TI  - [Violence, desire and death. Reflections on 3 taboos in psychiatry].
AB  - Few studies have assessed the links of violence, desire and death with psychiatry
      in a scientific way. Doctors are nonetheless regularly confronted with these
      situations which are particularly difficult to manage. It is not evident that
      psychiatrists are properly prepared to deal with them. This paper proposes an
      original analysis of the scientific literature related to violence, desire and
      death, and compares the attitudes of European and American doctors. RESULTS: 1)
      Violence: there is definitely a relationship between violence and mental
      disorder. Psychiatrists are particularly at risk of being assaulted by patients,
      especially at the beginning of their carrier (almost 50%). Violence also includes
      verbal and non-verbal threats, particularly in the emergency department.
      Psychiatrists are poorly trained to deal with this. 2) Desire: desire is
      widespread in psychiatry, and can lead to sexual contact between the patient and
      the therapist in 7 to 10% of cases. The outpatient setting carries the greater
      risk. Professional associations unanimously disapprove of such conduct but the
      ethics of posttermination sexual contact remains controversial. Sexual harassment
      of female doctors by patients is another form of desire (and of violence).
      Psychiatrists are also poorly trained to deal with desire. 3) Death: acute death
      occurs in psychiatry (e.g., suicide, substance intoxication and withdrawal,
      delirium, neuroleptic malignant syndrome, anorexia nervosa, dementia, lethal
      catatonia), and there is also a link between mental disorder and a higher
      incidence of natural mortality. Psychiatrists may thus be confronted with death,
      and the inpatient setting carries the greater risk. They are nonetheless poorly
      trained in thanatology. DISCUSSION: Psychiatric residents need better training to
      manage violence, desire and death. Poor training results in their exposure to
      dangerous situations and in inappropriate reactions. Acute management and primary
      prevention are needed. Acute management should include a collegiate approach, in
      order to avoid being the "target" of the patient or his/her family. Primary
      prevention comes through the breaking of the taboos which are still too frequent
      in Europe, even though the situation is different from the USA. It is important
      to lay down limits between psychiatry and violence, desire and death. Those
      situations should before all be better understood, and thereby research in this
      field have to be stimulated. The holding of consensus conferences in Europe is
      also important. CONCLUSION: There is an intimate relationship between violence,
      desire, death and psychiatry. This relation is too often neglected, as the poor
      training of psychiatrists underlines. The nature of the patient-doctor
      relationship have to be redefined according to those considerations.

PMID- 11294037
TI  - [Aging and cognitive slowing: example of attentional processes--evaluation
      procedures and related questions].
AB  - Slowing is generally associated to ageing. It appears in motor's functions and in
      cognitive tasks. What is the real nature of this slowing? Is it a general slowing
      concerning every cognitive processes with the same scale or is this slowing
      specific of only processes. Or, at least, is it of different magnitude for each
      cognitive processes? The aim of this paper is to present the state of this debate
      from results obtained in studies orientated toward attentional processes.
      Attention allows us to adapt oneself to environment that require in one hand
      selective mechanisms for pertinence events and in other hand inhibitory
      mechanisms for interferences. To evaluate these mechanisms priming and cueing
      procedures are used. Using primes (semantic or conceptual) results in shorter
      reaction time than for conditions without prime. In some experimental conditions,
      negative primes can be observed which results for longer reaction time. In these
      procedures, we need to be careful to the SOA's value (Stimulus Onset Asynchrony)
      (it represents the time between the end of the prime or cue presentation and the
      beginning of the stimulus presentation). The longer is the SOA, the shorter is
      the reaction time increase with a SOA between 200 ms and 400 ms. In these
      procedures, we now have to understand in the field of information processing what
      causes this reaction time modification. In other words, increase of reaction time
      with SOA could be explain increase of all stages of treatment or may be also the
      consequence of some abolition's of stages? In attentional procedures, we have to
      consider the automatic or controlled nature of cognitive processes. In target
      research tasks that implies selective attention, several authors have showed a
      distinction between automatic and controlled processing. Time to detect prompts
      increase generally with the distractor number excepted when the prompt is
      prominent for the subject (because of physical or emotional characteristics). In
      this second case, the pop out effect, reaction time does not depend from the
      number of distractors and this effect performs to be supervised by automatic
      processes. By contrast, reaction time variation is considered to be linked with
      controlled processes activation. What's about ageing? Myerson et al. (1992) don't
      show reaction time distinction between young and old in their meta analyse which
      really results from lexical decision tasks from 1980 to 1990. If you now consider
      the SOA values, results are less clear and contradictions existing between
      studies. Using negative priming procedures implies different results too, but one
      is main: it seems that elders take as much time to denote a prompt in conditions
      when prompt was distractor compared to neutral condition, by contrast to younger
      who take more time to denote the prompt where it was distractor compared to
      condition where it was not. Ageing effects on inhibition intensity and length
      could be expanded. Nissen and Corkin (1985) showed a facilitator effect with
      cueing in young and in old people, and this appears more important in old people.
      Hartley et al. (1990) show this results too and control the SOA: the facilitation
      size effect seems to depend from the SOA size. On top of that, some authors show
      the presence of the popout effect in elders but a reaction time lengthening when
      conditions imply controlled processing (visual or memory research tasks). In
      summary, the most studies show a slowing in old people whatever attentional tasks
      but the lengthening size doesn't vary systematically with conditions:
      facilitatory effects and automatic processing are possible but inhibitory
      processing are more probably impaired. Several hypotheses can explain these
      results. Some authors think there is a general slowing factor that slows with
      age. For others slowing depends from tasks, and mainly from several implied
      processing. Nevertheless, no one study show a regular relation between reaction
      time and priming or cueing effects. Few results, which we've presented in this
      article, are really compatible with the general slowing theory. Finally, McDowd
      and Birren (1990), or Hasher and Zacks (1988) suppose that there is an incapacity
      to ignore non pertinent information with ageing, but there are limit in this
      hypothesis too. In summary, we don't know at this time the real nature of slowing
      with age but experimental values seem to be in favour with slowing, which
      significance depends from cognitive processes. We now have to describe precisely
      slowing in old people, and more exactly with exact timing between prime and
      target could be a beginning of task.

PMID- 11294036
TI  - [Viewpoint of schizophrenic patients: a European survey].
AB  - The commercial introduction of atypical antipsychotic drugs for the treatment of
      schizophrenia constitutes a considerable step forward. However, despite the
      improved efficacy on all aspects of schizophrenia as well as improved
      tolerability, prescribers still appear to be reticent about substituting these
      agents for typical neuroleptics. With the appearance of these new drugs, the
      patient now occupies a central place in the management of schizophrenia. The
      patient is now considered as a true partner in the formulation and follow-up of
      the treatment programme, resulting in the need to determine the optimum
      therapeutic alliance. We present the results of a European survey concerning the
      effects of these new antipsychotic drugs comparatively with typical neuroleptics
      as perceived by schizophrenic patients themselves. For all patients participating
      in the survey, a new antipsychotic had been given in place of a typical
      neuroleptic for at least six months. Three-quarters of patients questioned
      considered that their new antipsychotic treatment would allow them to return to a
      normal life. Compared with the standard neuroleptics, patients felt that the new
      drugs had superior effects upon all dimensions of schizophrenia as well as a
      better safety profile, particularly as regards neurological side-effects. Because
      of the superior efficacy and safety profile, patients stated that they would be
      more inclined to follow their doctor's prescription implicitly, despite the fact
      that over 50% of these patients admitted to poor compliance with previously
      prescribed typical neuroleptics. This study focusing on the subjective experience
      of patients provides further arguments in support of the superiority of atypical
      antipsychotic drugs over typical neuroleptics, thus confirming available clinical
      trial data. The results of this study also pointed to the benefits of
      collaboration between doctor and patient, and questioning patients about their
      personal experience, which can then be taken into account when deciding upon and
      following up the therapeutic programme.

PMID- 11294038
TI  - [Microdeletion 22q11: apropos of case of schizophrenia in an adolescent].
AB  - Deletion of chromosome 22q11 concerns nearly 1/5.000 births, and is the most
      frequent interstitial microdeletion. The deletion generates various phenotypes
      which were initially regarded as distinct syndromes. 1) Di George syndrome was
      described in 1962 by immunologists, and associates thymic and parathyroid
      hypoplasia, cardiac malformation, and dysmorphic face; the prognosis is severe,
      as Di George syndrome is a life-threatening condition. 2) The velocardiofacial
      syndrome was described in 1978 by stomatologists, and associates palate
      abnormalities, cardiac malformations, dysmorphic faces, and learning
      disabilities. 3) The Takao syndrome was described in the late seventies by
      cardiologists as a clinical condition associating cardiac abnormalities and
      dysmorphic faces. During the nineties, a common molecular etiology was
      identified, and a new name proposed: CATCH 22, an acronyme for Cardiac
      abnormalities, Abnormal face, Thymic hypoplasia, Cleft palate, Hypocalcemia,
      deleted chromosome 22. Furthermore, new phenotypes have been recently recognized,
      most of them belonging to the psychiatric spectrum. Descriptive studies of large
      samples of children with 22q11 deletion, conducted, both in the United States and
      european countries, have shown the following pattern of associated symptoms:-
      abnormal face (100%), which expression varies with age, and can be discrete;-
      cardiac abnormalities (84%), including cardiac malformations of conotroncal
      types;--mouth abnormalities (49%), including cleft palate (14%), and velar
      dysfunction (20%);--urinary tract abnormalities (36%), including ureteric reflux,
      lung dysplasia;--transitory hypocalcemia (60%) mostly during infancy, and due to
      transitory hypoparathyroid dysfunction;--seizures (21%), which are usually a
      consequence of hypocalcemia;--immunodeficiency (1%), which worsens the prognosis.
      Deletion of chromosome 22q11 has been also associated with various psychiatric
      phenotypes, which can be classified into two groups, developmental abnormalities
      and psychiatric conditions. The great majority of patients with the deletion
      exhibit impairment of language and motor development, mild mental retardation,
      persistent coordination deficits, and poor academic performance. The deletion of
      chromosome 22q11 is also associated with high frequency of behavioral disorder
      with attention deficit during childhood, and with high frequency of psychotic
      disorder (bipolar disorder, and schizophrenia) during adolescence and young
      adulthood. The link between the 22q11 deletion and schizophrenia has been also
      supported by recent studies showing that the rate of 22q11 deletion in adults
      with schizophrenia (2%) is higher than it is in the general population. The rate
      may even be higher (6%) in subjects with childhood onset schizophrenia. The
      present work reviews the psychiatric literature associated with 22q11 deletion.
      We also report a case of 22q11 deletion in a 17-year-old girl that was initially
      diagnosed as paranoid schizophrenia. We will discuss the diagnostic, prognostic,
      and therapeutic consequences that such a genetic diagnosis implies. In the case
      reported here, transitory hypocalcemia induced: 1) dystonic symptoms that was
      believed to be catatonic symptoms or neuroleptic secondary effects, by
      clinicians; 2) a poor response to neuroleptic medication.

PMID- 11294039
TI  - [Glutaminergic hypothesis of schizophrenia: clinical research studies with
      ketamine].
AB  - Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartate
      (NMDA) receptor is involved in schizophrenia pathophysiology. Post-mortem studies
      have revealed a lower density of glutamatergic receptors in patients with
      schizophrenia. Other studies of cerebrospinal fluid reported lower levels of
      glutamate in patients with schizophrenia in healthy comparison subjects. The most
      compelling evidence is provided by the psychomimetic effects of the NMDA
      antagonists phencyclidine and ketamine. Recently, much interest has been given to
      the study related to the role of NMDA receptor in pathophysiology of
      schizophrenia by administration of sub-anesthetic doses of ketamine. A
      phencyclidine hydrochloride derivate, ketamine, is a dissociative anesthetic and
      a non competitive antagonist of the NMDA receptor. In healthy subjects, ketamine
      produces: 1) positive symptoms of psychosis, such as illusions, thought disorder
      and delusions; 2) negative symptoms similar to those associated with
      schizophrenia including blunted emotional responses, emotional detachment, and
      psychomotor retardation; 3) cognitive impairments, in particular impairments on
      tests of frontal cortical function including increased distractibility, reduced
      verbal fluency and poorer performance on the Wisconsin Card Sorting Test. During
      smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities
      which are among the characteristics of schizophrenia. In patients with
      schizophrenia, the administration of ketamine produces an activation of their
      psychotic symptoms, which have striking similarities to symptoms of their usual
      psychotic episodes. Ketamine effects on memory and other cognitive functions in
      schizophrenic patients are controversial. The psychomimetic effects of ketamine
      are transitional, reversible and influenced by time, dose and administration
      conditions. Susceptibility to the psychotomimetic effects of ketamine is minimal
      or absent in children and becomes maximal in early adulthood. The similarity
      between ketamine effects and endogenous psychoses created interest in the
      capacity of antipsychotic medications to block ketamine effects. Haloperidol
      failed to block this ketamine-induced psychomimetic effects in healthy subjects
      and in schizophrenic patients. However, clozapine, the prototype of atypical
      antipsychotic agents significantly reduced the ketamine-induced increase in
      positive symptoms in schizophrenic patients. Recently, lamotrigine significantly
      decreased ketamine-induced positive and negative symptoms in healthy subjects.
      Brain regions responsible for NMDA-mediated psychosis have not been established.
      Using positron emission tomography and [18F] fluorodeoxyglucose, the sub
      anesthetic ketamine administration produces bilateral increases in metabolic
      activity in the prefrontal cortex. In a [15O] H2O positron emission tomography
      study, ketamine selectively increases cerebral blood flow in the anterior
      cingulate cortex and reduces cerebral blood flow in the hippocampus and primary
      visual cortex. The mechanism of neuropsychiatric effects of sub-anesthetic
      ketamine is not clear. A dysfunction in glutamate-dopaminergic interactions has
      been suggested as a mechanism for these effects of ketamine. Ketamine has been
      reported to primarily block NMDA receptor complex giving support to a glutamate
      deficiency hypothesis in schizophrenia. In addition, ketamine caused increases in
      cortical and striatal synaptic dopamine concentrations. The effects of NMDA
      receptor antagonist administration are argued to support a neurobiological
      hypothesis of schizophrenia, which includes pathophysiology within several
      neurotransmitter systems, manifested in behavioral pathology. Pharmacological
      modulation of the effects of NMDA receptor antagonists, such as ketamine, may
      lead to development of novel therapeutic agents for psychiatric illnesses such as
      schizophrenia.

PMID- 11294040
TI  - [Early maladaptive processes, depression and alexithymia in suicidal hospitalized
      adolescents].
AB  - Alexithymia characterizes people having important difficulties in putting their
      feelings and moods into words. Adolescents' depression shows some peculiarities:
      one of them, which is often observed, is the equal difficulty of imparting one's
      feelings to others. This research concerns adolescents who attempted suicide. We
      study classical factors: depression and hopelessness. But our main objective is
      at first to study the relationship between attempted suicide, depression,
      hopelessness and alexithymia. The second objective of our study deals with the
      the prominent part of early schematas in this complex inter-relation.
      Maladaptative early schematas are no doubt involved in dysfunctional schematas
      found in depression and hopelessness. As a consequence, we would like to verify
      the following hypothesis: maladaptative early schematas are very numerous and
      specific among adolescents who attempted suicide. These schematas are the core of
      the complex inter-relation between attempted suicide, depression, hopelessness,
      suicide risk, suicide relapse and alexithymia. We have compared a group of normal
      subjects (who did not try to take their owns lives) and a group of people who
      did. First, we have found that the latter are more prone to alexithymia: a large
      majority of these subjects exceeds by far the accepted norm of the Toronto
      Alexithymia Scale. We have proved that the subjects who have attempted suicide
      also accumulate maladaptative early schematas. The qualitative analyse of these
      schematas leads to a possible explanation of the tendency to self destruction.
      Moreover there are apparently important differences between subjects who, in the
      past-experienced or did not experience a major depressive episode. The analysis
      of the relationships between the various factors of our study brings us to the
      conclusion that there is an unmistakable causal link between maladaptative early
      schematas and the interactive set (depression-hopelessness-major depressive
      episode-alexithymia) all these being part of attempted suicide and forming an
      integrant part of a whole which is the vulnerability to the suicide. Studying the
      various steps of early schematas seems to be quite promising as far as depression
      and suicide are concerned.

PMID- 11294041
TI  - [Comparative study of paroxetine and mianserin in depression in elderly patients:
      efficacy, tolerance, serotonin dependence].
AB  - The primary objective of this multicentre, randomized, double-blind study carried
      out in France was to compare the efficacy and safety of a 6-week treatment with
      paroxetine (20 mg/day) or mianserine (30 mg/day) in geriatric hospitalized or
      ambulatory patients (> or = 60 years) treated for a major depressive disorder
      (according to DSM III-R). A secondary objective was to discriminate those items
      predicting the response to an agent according to its serotoninergic or
      noradrenergic pharmacologic profile. The tool used for this latter purpose was
      the Aubin-Jouvent-Rating-Scale (AJRS) which was designed to assess the deficit of
      serotonin: this is a scale with 10 items, some of them regrouped into a "general"
      factor (irritability, sudden mood change, impatience, aggressivity) or a
      "depression" factor (pain, anxiety, suicidal ideas) with additional items related
      to sleep disorders, abnormalities in eating behavior and inability to tolerate
      isolation. In the perspective of this assessment, paroxetine was chosen due to
      its potential to inhibit serotonin re-uptake, as compared to mianserin which
      blocks presynaptic alpha-adrenergic receptors with negligible action on
      serotonin. This was a multicenter study carried out in France in 50 hospital or
      private practice psychiatrists. The assessment criteria included the MADRS, the
      AJRS, the COVI's anxiety scale, the Folstein's Mini-mental state (MMS) as well as
      a global assessment by the investigator at the end of the study. Safety was
      measured with a nondirective questionnaire, routine laboratory tests as well as a
      global assessment by the investigator. The primary efficacy criteria was the
      change in the MADRS global score. Statistical analysis included chi-square or
      Fisher's test as well as Student's and Wilcoxon tests for comparability at
      baseline, and analysis of variance for the changes in scores as during the study.
      A total of 116 patients was randomised (paroxetine: 54; mianserine: 62), of whom
      96 completed the study (paroxetine: 43; mianserine: 53). With the exception of
      MADRS moderately higher in the paroxetine group, both groups were comparable at
      baseline. After 6 weeks of treatment, a marked improvement was recorded in both
      groups for all criteria except MMS; there was a consistent tendency favouring
      paroxetine which reached statistical significance for the COVI' scale (p =
      0.001). For a given criterion, the difference paroxetine versus mianserine
      appeared related to the score at baseline; it was also more marked in those
      patients with a AJRS baseline score > or = 20 with a difference for MADRS
      reduction of marginal significance in favor of paroxetine (p = 0.061). As regards
      safety, at least one adverse event was reported in 31.5% of the patients
      receiving paroxetine versus 41.9% in those receiving mianserin (NS); premature
      withdrawal related to an adverse event was reported in 11.1% of the patients in
      the paroxetine group versus 12.9% in the mianserin group. No abnormality of
      clinical significance was reported in either group concerning laboratory tests.
      In conclusion, this study confirmed the therapeutic value and good safety of
      paroxetine as an antidepressant in geriatric populations, especially when exist a
      concomitant anxiety or symptoms likely to reflect a deficit of serotonine
      (irritability, emotional lability, restlessness, aggressivity) and to predict a
      good response to an agent such as this one.

PMID- 11294042
TI  - Prevalence of obsessive compulsive symptoms (OCS) in a sample of Egyptian
      adolescents.
AB  - The aim of this work was to determine the prevalence of OCS among a community
      sample of Egyptian students. The sample was selected using a multistage
      stratified random sample of students from El Abasseya educational area in Cairo.
      The tools used in this study included the General Health Questionnaire for
      screening of psychiatric morbidity and the Arabic Obsessive Scale for obsessive
      traits. The Yale Brown Obsessive Compulsive Scale was used to determine the
      profile of OCS and the ICD-10 research criteria for diagnosis of OCD among OCS
      positive subjects. The prevalence of psychiatric morbidity among the total sample
      was 51.7%, whilst that of obsessive traits was 26.2% and that of obsessive
      compulsive symptoms was 43.1%. OCS were more prevalent among the younger
      students, among female students and first born subjects. Aggressive,
      contamination and religious obsessions and cleaning compulsions were the
      commonest among the sample; 19.6% of subjects with OCS fulfilled ICD-10 criteria
      for OCD.

PMID- 11294043
TI  - [Determinants of compliance with antidepressive drugs].
AB  - A national survey was conducted in a representative sample of the general French
      population in order to assess antidepressant non compliance frequency and the
      factors that influence it. Two types of noncompliance were taken into account: 1)
      the premature interruption of the treatment; 2) the omission of doses. Data were
      collected by phone interview. Results show that 36.9% of the 423 included
      subjects (who represent 4.3% of the sample) were noncompliants (15.4% by
      treatment interruption and 21.5% by dosage modification). The two types of
      noncompliance have different risk factors. Treatment interruption was more
      frequent for patients with high level of schooling (OR = 2.5), in case of
      multiple take regimens (OR = 3), when the physician did not informed the patient
      about treatment (OR = 3.3) and when the patients' sources of information were
      exclusively non medical ones (OR = 3.7). Dosage modification was more frequent in
      female (OR = 2.1), when the treatment duration exceeded six months (OR = 2.5) and
      when the prescriber did not communicate with the patient relatives (OR = 1.8).
      The information delivered by the physician about the duration of the treatment
      was associated with the two types of compliance but with an opposite effect. This
      information has a protective effect on treatment interruption (OR = 0.5) but
      increases the risk of dosage modification (OR = 1.1).

PMID- 11294044
TI  - [A non-infectious pyodermatitis: Pyoderma gangrenosum].
AB  - Pyoderma gangrenosum (PG) is a rare chronic inflammatory skin disease
      characterized by the recurring development of necrotizing and painful ulcers. The
      skin lesions appear spontaneously or after minor traumatic injuries. Sites of
      predilection include the lower limbs and the trunk but any part of the body may
      be affected. PG is not an infectious disease; although the etiology is not
      completely understood, an immune disturbance is certainly involved. An underlying
      systemic disorder is associated in up to 50% of the cases, specially inflammatory
      bowel diseases, arthritis, paraproteinemias and hematologic malignancies. Chronic
      venous or arterial ulcers as well as bacterial gangrene are the most frequent
      false diagnoses. A right diagnosis, based upon the distinctive clinical features
      and a compatible histology, is essential to avoid surgical procedure that often
      tends to exacerbed the process. Because of its persistent and recurrent nature,
      systemic long-term therapy based upon corticosteroids associated with sulfones or
      immunosuppressive agents is required.

PMID- 11294045
TI  - [Therapeutic housing: tools of psychiatric networks].
AB  - Insufficient transitional structures between psychiatric hospitals and return to
      social life, has for quite some time proved a handicap toward the social
      integration of mentally disabled people. Asylum confined psychiatry is on the way
      out and slowly evolving into an ever widening projection in social life. The
      monitored residences and supervised flats are a striking example of such
      evolution. For stabilised psychiatric patients they represent a real hope of
      increased autonomy leading to an adaptation to psychosocial integration.

PMID- 11294046
TI  - [How I explore ... the risk of metastasis from melanoma].
AB  - The development of new therapeutic protocols for malignant melanoma calls for an
      upgraded assessment of the individual risk to develop metastases. The predictive
      sentinel lymph node method is best practiced in a multidisciplinary approach. The
      selective lymphadenectomy of the first draining lymph node is followed by
      minutely detailed histologic examination combined with immunohistochemistry.

PMID- 11294047
TI  - [Pharmacy clinics. Medication of the month. Meningitec].
AB  - Meningitec (Wyeth Lederle) is a new antimeningococcal C conjugate vaccine. This
      vaccine contains a group C meningococcal oligosaccharide coupled to a carrier
      protein (CRM197, a non toxic variant of diphteria toxoid). This vaccine has been
      shown to be immunogenic both in adults and young children. Meningitec is well
      tolerated and its efficacy has been recently demonstrated in England (vaccine
      efficacy: 97% among adolescents; 92% among toddlers).

PMID- 11294049
TI  - [Image of the month. A cerebral venous thrombosis].

PMID- 11294048
TI  - [Clinical study of the month. The CALM study assessing the combination of an
      angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist
      in the treatment of diabetic nephropathy].
AB  - The main objective of the CALM (Candesartan And Lisinopril Microalbuminuria)
      study is to assess the effect of a dual blockade of the renin-angiotensin system-
      using both an angiotensin converting enzyme inhibitor (ACE-I) and an angiotensin
      II type 1 receptor blocker--in patients with type 2 diabetes, high blood pressure
      and microalbuminuria. The study included 200 patients randomized to receive
      candesartan 16 mg or lisinopril 20 mg for 12 weeks, followed by 12 weeks of the
      same monotherapy or a combination treatment. Main outcomes are the reduction of
      microalbuminuria and blood pressure. All three of the treatments are effective,
      but the dual blockade is respectively 18%, 8 mmHg and 5 mmHg more effective in
      reducing microalbuminuria, systolic and diastolic blood pressure. No comparison
      is made between this "new" association and the more frequently used biotherapy
      (i.e. ACE-I plus thiazidic diuretic) and therefore its usefulness in regular
      practice is still to be determined.

PMID- 11294050
TI  - [Pharmacy clinics. How I treat...arthritis. First part: pathophysiologic
      recurrence and symptomatic treatment].
AB  - Osteoarthritis is now considered in all developed countries as a major burden for
      public health. During several years, the pharmacological management of
      osteoarthritis mainly focused on symptoms relief without interaction with the
      long-term structural progression of this disease. Based on recently published
      consensus, the present article summarizes the currently available options in the
      symptom-modifying management of osteoarthritis.

PMID- 11294051
TI  - [Clinical case of the month. Von Hippel-Lindau disease].
AB  - VHL disease is a rare genetical disease with a poor long-term prognosis. Clinical
      features include retineous angiomas, CNS hemangioblastomas, pheochromocytomas and
      renal cysts. Renal cysts are bilateral and frequently lead to malignant
      transformation. Surgical treatment of renal cysts is preferably delayed until a
      minimum of 3 cm diameter has been reached. Treatment has to be as conservative as
      possible, knowing that uni- or bilateral nephrectomy often has to be carried out
      later.

PMID- 11294052
TI  - [Autoimmune thyroiditis].
AB  - The continuum of clinical phenotype between different autoimmune thyroid diseases
      and mainly the common pathophysiological mechanisms have lead to a novel
      classification of these disorders into three types: (1) Type 1 autoimmune
      thyroiditis (euthyroidism associated with the presence of anti-thyroglobulin and
      anti-thyroperoxydase autoantibodies); (2) Type 2 autoimmune thyroiditis or
      Hashimoto's disease (hypothyroidism with anti-thyroglobulin and anti
      thyroperoxydase autoantibodies). Postpartum thyroiditis falls into this category
      and is characterized by transient hyperthyroidism followed by hypothyroidism; and
      (3) Type 3 autoimmune thyroiditis or Graves-Basedow's disease (hyperthyroidism
      with anti-TSH receptor "stimulating" auto-antibodies, often associated with anti
      thyroglobulin and anti-thyroperoxydase autoantibodies). Thyroid orbitopathy often
      complicates Type 3 autoimmune thyroiditis and is thought to result from an
      autoimmune response against an autoantigen common to thyroid and orbital
      fibroblasts/adipose cells. We present the actualized knowledge about the
      immunological parameters that can be detected and quantified in autoimmune
      thyroid diseases, about the pathophysiological mechanisms involved in these
      disorders, and about the options of their treatment that are currently offered to
      the medical community.

PMID- 11294053
TI  - [Emergency medicine: general principles governing the hospital management of
      victims of multiple trauma].
AB  - The management of the trauma victim admitted to the emergency department must be
      rapid and efficient. Within the first hour, vital functions must be stabilised
      while a systematic survey of all injuries is carried out. This survey must be as
      complete as possible, and depends on the patient's status and response to initial
      resuscitative measures. The need for urgent surgical intervention, therapeutic
      radiology, or other treatment modalities must be quickly established. This
      systematic approach, which follows a seven step sequence, can only be carried out
      by a well-trained team. Because at this time emergency and SMUR are often staffed
      with general practitioners, and because the trauma centers do not yet exist in
      Belgium, the application of the treatment protocol presented in this paper is a
      pre-requisite to quality of care for these patients. It is the only means to end,
      once and for all, the improvised or intuitive, and often erroneous, approach to
      these patients.

PMID- 11294054
TI  - [A study of the risk of melanoma in 3,695 primary school students in Liege].
AB  - An epidemiological survey was performed in pupils from primary schools of Liege
      in order to better identify risk factors for photobiological alterations prone to
      induce cutaneous melanoma in adult life. Phenotypic and behavioral factors facing
      up to sun exposure were considered. In a 4-level risk scale, about half of the
      Liege children showed a high to severe risk at photobiological alterations. Thus
      melanoma prevention requires a sustained effort in the Mosan region, particularly
      by health education programs at school.

PMID- 11294055
TI  - [Lyme disease and facial paralysis in children].
AB  - Lyme disease is one of the most common cause of acute peripheral facial palsy in
      children. Overall nervous system involvement is also the predominant
      manifestation of Lyme disease in children, chiefly as facial palsy and/or aseptic
      meningitis. The medical records of ten patients with discharge diagnosis of
      facial palsy associated to borreliosis were retrospectively reviewed. The
      diagnostic criteria for borreliosis included acute peripheral facial palsy
      associated with erythema migrans (1/10) and/or positive Lyme serology in serum
      (10/10) or CSF (6/10). Facial palsy was associated with a high rate (9/10) of
      occult meningitis. Cerebrospinal fluid findings showed lymphocytic pleocytosis
      associated to moderate increased protein level. PCR assays displayed a very low
      sensitivity. All patients with meningitis were treated with intravenous
      ceftriaxone for 3 weeks and received their treatment as outpatients with an
      heparinised venous catheter. Our study confirm that borreliosis should be
      considered in every case of peripheral facial palsy and based on the high rate of
      occult meningitis, we also advocate to perform a lumbar puncture. Although long
      term prognosis of facial palsy associated with Lyme disease in children appears
      excellent, current treatment recommendations advocate prolonged antibiotic
      therapy.

PMID- 11294056
TI  - [Thoracic outlet syndrome].
AB  - Thoracic outlet syndrome (TOS) is due to compression/irritation of brachial
      plexus elements ("neurogenic TOS") and/or subclavian vessels ("vascular TOS") in
      their passage from the cervical area toward the axilla. The usual site of
      entrapment is the interscalenic triangle. TOS is a highly controversial subject
      in regard to its incidence, diagnostic criteria and optimal treatment.
      Constitutional factors--osseous or more often fibromuscular--and external factors
      such as trauma predispose to the development of TOS. Various clinical pictures
      include pain in the cervical region and arm, paresthesias, aggravated by overhead
      positions of the arms, hand intrinsic muscle deficit/atrophy, easy fatiguability,
      paleness, coldness of hand. The clinical examination may be entirely normal or
      show cervical and scapular muscle spasm, tenderness of supraclavicular area,
      radial pulse attenuation upon positional maneuvers, sensory and/or motor deficit,
      usually of C8/T1 distribution. The diagnosis is based on clinical evaluation and
      absence of other relevant pathology. Sometimes TOS can enhance symptoms
      consecutive to cervical or supraclavicular lesions. Cervical spine and distal
      peripheral nerves are investigated by radiological and electrophysiological
      studies. Unless there is significant motor deficit or subclavian artery
      compression, the treatment should be kept conservative as long as possible, by
      adapted physical therapy. In case of neurological deficit or symptoms
      unresponsive to medical treatment, the patients will--like in other nerve
      entrapment syndromes--be helped by decompressive surgery, nowadays preferably
      performed via an anterior supraclavicular approach.

PMID- 11294057
TI  - Negative symptoms in patients with schizophrenia with special reference to the
      primary versus secondary distinction.
AB  - Negative symptoms in schizophrenia represent a diagnostic and therapeutic
      challenge. Diagnostically, they need to be differentiated from depression and
      treatment-related variables. The latter include akinesia, a part of drug-induced
      Parkinsonism, sedation, and effects of understimulation, as they have been
      reported in patients institutionalised for long periods of time. Other patients
      show negative symptoms as sequelae of positive symptoms: Commanding voices that
      tell patients to stay in the house or forbid them to speak to other people, or
      persecutory delusions may result in social withdrawal and alogia. All of the
      above, often summarised as secondary negative symptoms, have to be distinguished
      from primary negative symptoms, sometimes also referred to as the deficit state
      of schizophrenia. These are considered illness inherent problems and usually have
      an enduring, chronic course. They are often seen in the absence of positive
      symptoms, as in simple schizophrenia. The chronicity of the disorder, the lack of
      obviously disturbed and aberrant behavior and the fact that these patients tend
      to lead secluded lives lead to an underrepresentation of these patients in
      clinical psychiatry. Next to a description of clinical symptoms a review of means
      to aid differential diagnosis is provided. Negative symptoms call for sound
      differential diagnosis provided by a specialist in order to be able to provide
      optimal management to prevent the negative consequences of a chronic negative
      syndrome.

PMID- 11294058
TI  - What is the schizophrenic patients' level of information about their disease and
      their treatment?
AB  - Improved compliance with antipsychotic medication is a major issue in
      schizophrenic management. For this purpose educational programs have been used,
      but up to now, little or no information has been gathered or published in France
      concerning schizophrenic patients' opinion on information they have about their
      disease and their treatment. Thus we conducted a survey in concert with 78
      psychiatrists from the French psychiatric health service. From this cross
      sectional survey we assessed 336 outpatients (male: 72%; mean age: 36 +/- 10.4
      years) with schizophrenia according to the DSM IV (paranoid sub type: 57%,
      disorganized: 12%, catatonic: 1%, undifferentiated: 12%, residual: 18%). The mean
      duration of the illness was 11.6 years (sd: 8.5) and the mean duration of the
      follow up with the same psychiatrist was 5.4 years (sd: 5.1). Patients completed
      a questionnaire which assessed their level of information on mental illness and
      treatment. The diagnosis of schizophrenia has been told to their patients by 39%
      of the psychiatrists, and treatment has been explained to the patients by 96% of
      the practitioners. Results indicate less than half of the patients (45%) felt
      ill, only 46% thought they knew their illness well or very well (nevertheless
      only 31% of them named spontaneously the diagnosis of schizophrenia or
      psychosis), and 61% considered that they had been given sufficient information.
      Most of the patients (79%) were persuaded that their treatment was useful, and
      75% of patients were completely satisfied with their treatment. Surprisingly 92%
      reported taking their medication regularly. Most patients think that a high level
      of information about their illness (74%) and treatment (79%) help them to cope
      better with their schizophrenia. Analysis performed according to patients
      characteristics indicated that paranoid patients felt more ill (p = 0.035) than
      others, thought to know less about their illness (p = 0.0065), and were less
      satisfied with their treatment (p = 0.04) and their level of information (p =
      0.03). Patients with a duration of their illness longer than 10 years were more
      convinced of the utility of their treatment (p = 0.02) and had debated more on
      the choice of their treatment with their psychiatrist (p = 0.047). Patients older
      than 35 years were more satisfied with their information (p = 0.002). More
      patients with atypical antipsychotics accepted to take their treatment on a
      regular basis (p = 0.035) compared to patients under classical neuroleptics. This
      survey underlines that mental health consumers' opinions can be obtained even in
      the field of schizophrenia, and argues in favour of further such investigations.
      It also highlights the need for educational programs on schizophrenia and
      antipsychotic medications.

PMID- 11294059
TI  - From psychiatric hospital to rehabilitation: the Nordic experience.
AB  - Deinstitutionalization and decentralization in psychiatry have by now been the
      first items of the agenda for more than 30 years. A theory of social psychiatry
      with social rehabilitation and reintegration was the underlying basis for the
      activities which should make the change from mainly inpatients to community-based
      outpatients treatment possible. By means of the National Danish Psychiatric Case
      Register this paper shows how the process mostly has concentrated on the
      deinstitutionalization (or reinstitutionalization?) of the old long-stay
      psychiatric patients. A new but smaller group of long-stay patients has appeared
      in the statistics. The average age of this group is 40 years compared to the old
      long-stay patients' average age of 60 years. It is also shown that the
      readmission rate during the first year after the discharge following the
      hospitalization during which the schizophrenia diagnosis was given for the first
      time ever is almost unchanged (with a small increase) for both males and females.
      So, in Denmark it is on average between 45% and 50% for females and males
      respectively. A break down on these data on counties shows that the situation
      varies broadly from a little over 30% for the best (mainly rural counties) to a
      maximum of 54%. It seems as if social psychiatry in the Nordic countries mainly
      concentrate on social care and only to a less degree on network, employment and
      other basic rehabilitation and reintegrative social work. A basis for a
      successful social integrative work must be a treatment initiated as early as
      possible with an antipsychotic treatment and maximum of compliance.

PMID- 11294060
TI  - Which role for amisulpride in rehabilitation of schizophrenic patients with acute
      exacerbation?
AB  - Amisulpride is a substituted benzamide derivative with selective binding to the
      D2/D3 dopamine receptor. In patients, a beneficial effect on negative signs has
      been demonstrated for doses up to 300 mg daily. On the other hand, amisulpride
      demonstrate efficacy in the treatment of classical form of schizophrenia at
      higher doses (400 to 800 mg/day up to 1,200 mg/day at the maximum). Five studies
      that included acutely ill schizophrenic patients are reviewed. All were double
      blind, randomized parallel group studies and the primary efficacy criterion was
      the BPRS total score. In these study amisulpride was at least as efficacious as
      haloperidol (10-30 mg), risperidone (8 mg daily), or flupentixol (25 mg daily) in
      controlling positive symptoms, but was significantly more effective than
      haloperidol on secondary negative symptoms. When quality of life (QLS) was
      assessed, amisulpride led to a better improvement than haloperidol. In the long
      term treatment of schizophrenia, amisulpride maintained antipsychotic efficacy
      over a 12-month period in an open randomized study. In this study, amisulpride
      led to a better improvement on Global Assessment of Functioning than haloperidol,
      the standard reference drug. Furthermore, amisulpride has a favorable
      benefit/risk profile and induces fewer extrapyramidal side effects than
      haloperidol the standard reference drug. Therefore, amisulpride is proposed for
      first-line treatment of schizophrenia in acute exacerbations. It contributes to
      favor a better social rehabilitation of schizophrenic patients.

PMID- 11294061
TI  - Molecular basis of Lewis blood type in Taiwanese.
AB  - The Lewis (Le) histo-blood group system comprises two major antigens, Le(a) and
      Le(b) which are determined by alpha (1,2)-fucosyltransferase (FUT2) and alpha
      (1,3/1,4)-fucosyltransferase (FUT3). In this study, we analyzed the mutations of
      FUT2 and FUT3 genes in 101 Taiwanese by molecular biology method and compared
      them with their serologic phenotypes to explore their relationship. There is at
      least one wild allele of FUT2 and FUT3 genes in phenotype of Le (a-b+). The
      phenotypes of Le (a+b-) and Le (a+b+) are caused by mutations of both alleles of
      FUT2 gene and at least one wild allele of FUT3 gene. The genotypes of Le (a+b-)
      and Le (a+b+) are the same. Twenty cases are phenotype of Le (a-b-), which are
      caused by mutations of both alleles of FUT 2 gene and/or FUT 3 gene. Twelve cases
      were caused by both alleles mutations of FUT 3 gene only, while three cases were
      caused by mutations of both alleles of FUT2 gene and the rest of the cases were
      caused by mutations of both alleles of FUT2 and FUT3 genes. Our findings confirm
      that the Le histo-blood group is determined by the interaction of FUT 2 and FUT 3
      genes. Our report is the first study of FUT 2 gene and FUT 3 gene in a Taiwanese
      population. We suggest that the genetic analysis of Le blood group should include
      FUT 2 and FUT 3 genes together.

PMID- 11294062
TI  - Validation of the Chinese Health Questionnaire (CHQ-12) in community elders.
AB  - There has been no validated screening instrument for use in non-psychotic illness
      of the elderly in Taiwan. This study aims to test the validity of the 12-item
      Chinese Health Questionnaire (CHQ-12) among the elderly in a community study. The
      CHQ-12 was administrated via reading-out to 222 subjects aged 65 and over from
      three communities. Psychiatrists using the Geriatric Mental Status Schedule (GMS)
      assessed psychiatric condition while the diagnosis was made according to the
      computerized program, AGECAT. Validity indices of the CHQ-12 were calculated,
      using the Relative Operating Characteristic (ROC) analysis for its optimal cut
      off point. Variables hypothesized to affect its performance were assessed.
      Validity of the CHQ-12 at optimal cut-off point 2/3 were estimated with a
      sensitivity of 79.7%, a specificity of 83.6%, a positive predictive value of
      68.9%, a negative predictive value of 90.0% and an overall misclassification rate
      of 17.6%, and an estimate of the area under the ROC curve of 0.81. The
      performance of the CHQ-12 was better in males, in those who were literate, and in
      those without any physical illness. This study demonstrated that the use of CHQ
      12 in the elderly community is as valid as in the general population survey.
      However, it should be read out by the investigator rather than self-administered
      due to the high proportion of illiteracy among the Taiwanese elderly.

PMID- 11294063
TI  - The consistency and reliability of periodontal bone level measurements using
      digital scanning radiographic image analysis--a pilot study.
AB  - The purpose of the present study was to evaluate the consistency and reliability
      of alveolar bone height measurement using digital scanning radiographic image
      analysis (DSRIA). A randomly selected (standardized paralleling technique)
      periapical radiographs of 20 molar teeth (10 maxillary molars and 10 mandibular
      molars) from 178 individuals with periodontitis were reporting or referred to the
      patient population of the dental clinics of the teaching hospital. Radiographic
      measurements were performed and read by two examiners, with a separation time of
      three weeks of different tooth groups and as established by double reading of 20
      molar teeth in 10 individuals using the DSRIA. The calculating data of
      radiographic alveolar bone loss (RABL) measured and analyzed by the DSRIA for
      each molar group were compared based on the inter- and intra-examiners' data. The
      means and standard deviations were calculated to compare radiographs of the inter
      and intra-examiners' groups. The reliability coefficients were computed to
      assess the consistency and reliability for each molar group. The results revealed
      that the intra- and inter-examiners' reliability coefficients ranged from 0.986
      to 0.995 (p < 0.001, significantly different from 0). An excellent
      reproducibility was indicated in maxillary molar, mandibular molar and of both
      arches, respectively. It was concluded that the standard periapical radiograph
      using the DSRIA has the potential to be a valuable and reliable method in
      measuring linear alveolar bone defects caused by periodontitis.

PMID- 11294064
TI  - The determinants of safe sex behaviors of junior college students with sexual
      experience.
AB  - The purpose of this study was to explore the safe sex behavior and related
      factors of junior college students with sexual experience in southern Taiwan.
      This study used a cross-sectional design, in which data from a sample of 187
      junior college students with sexual experience were collected by an anonymous and
      self-administered questionnaire. For a conceptual framework, the study used
      constructs from the PRECEDE (Predisposing, Reinforcing, and Enabling Causes in
      Educational Diagnosis and Evaluation) model. Two predisposing factors (AIDS
      prevention self-efficacy, AIDS related knowledge), one enabling factor (school
      resources in AIDS prevention), one reinforcing factor (perception of peers' AIDS
      prevention behavior), demographic characteristics (gender, parents' educational
      level), substance use (cigarette and alcohol use) and sexual history (age of
      first sexual intercourse, number of sexual partners) were examined for their
      ability to influence safe sex behavior of junior college students with sexual
      experience. The results showed that gender, fathers' educational level, age of
      first sexual intercourse, number of sexual partners, cigarette use and alcohol
      use were significant factors for difference in safe sex behavior. AIDS prevention
      self-efficacy, AIDS-related knowledge, and perception of peers' AIDS prevention
      behavior were all positively related to safe sex behavior. AIDS prevention self
      efficacy, fathers' educational level accounted for 49.8% of the variance in safe
      sex behavior.

PMID- 11294065
TI  - Laparoscopic subsegmentectomy for hepatocellular carcinoma with cirrhosis: a case
      report.
AB  - Laparoscopic liver resection is feasible for both benign and malignant disease
      with present laparoscopic techniques and technology. Laparoscopic liver tumor
      resection is indicated instead of the conventional hepatectomy if the tumor is
      located in the peripheral part of the liver. Here, we reported a case of a 73
      year-old woman who accepted laparoscopic subsegmentectomy for hepatocellular
      carcinoma of segment 6. After traditional laparoscopic trocar was settled down
      under the low pneumoperitoneal pressure of 8 mm Hg, laparoscopic ultrasound
      allowed exact localization of lesions first and then transection line was marked.
      Then, dissection the liver parenchyma was carried out with laparoscopic microwave
      coagulator and ultrasonic aspirator gradually. After operation, she resumed full
      diet on the second day and was discharged on the 5th post-operative day with no
      complications and high patient satisfaction. She had follow-up study regularly in
      our clinic and was disease free at nine months. With the improvement of
      laparoscopic techniques and the development of new and dedicated technologies,
      laparoscopic hepatectomy has become feasible.

PMID- 11294066
TI  - Discrete subaortic membranous stenosis--a case report.
AB  - Isolated subaortic stenosis is a rare type of cardiac anomaly which has been
      characterized as having two types: the discrete type, including membranous or
      fibromuscular, and the tunnel type. In the discrete type, a crescent-shaped,
      fibrous curtain is attached to the ventricular septum or completely encircles the
      left ventricular outflow tract and can be located anywhere from immediately below
      the aortic valve to 10 mm or more into the body of ventricle. A 22-year-old
      female presented at our hospital with a divided PDA, a murmur that was found by
      incident and progressive exertional dyspnea. Echocardiography revealed left
      ventricular hypertrophy, moderate aortic insufficiency, and severe aortic
      stenosis characterized by a thickened aortic valve and membranous type subaortic
      stenosis with a transmembranous high pressure gradient, 121 mmHg. An operation to
      replace the aortic valve and excise the membranous collar was performed with
      cardiopulmonary bypass support. The patient did well during the postoperative
      follow-up period. If the preoperative LVOT pressure gradient had been higher than
      45 mmHg, the incidence of recurrent stenosis, progression of aortic regurgitation
      and the need for reoperation would have been higher. In order to prevent this
      from happening, we chose to replace the defective valve with a mechanical valve
      and enucleate the discrete lesion.

PMID- 11294067
TI  - Percutaneous release of abductor pollicis brevis muscle fibrosis in a bowler--a
      case report.
AB  - The authors reported a patient with abductor pollicis brevis muscle fibrosis of
      the right thumb, stemming from a bowling injury that had occurred 6 years
      previously. At that time in the acute stage, a Chinese bonesetter treated the
      injury using manipulation, massage and herbal drugs. Abduction contracture of the
      patient's right thumb developed. She began to experience chronic pain at dorsal
      side of her right thumb and discovered that she could not move her thumb into a
      retro position. When she came into our hospital, physical examination revealed an
      abduction contracture of patient's right thumb, the angle of separation was 60
      degrees, and the angle of circumduction was fixed at 90 degrees. In addition, a
      fibrotic band was palpable in abductor pollicis brevis muscle. The patient
      responded well to percutaneous release and physical therapy. As far as we know,
      this is an unusual case, which has not been reported before.

PMID- 11294068
TI  - Pharmacological treatments of autism, attention deficit hyperactivity disorder,
      oppositional defiant disorder, and depression in children and youth--commentary.

PMID- 11294069
TI  - What does the MTA study tell us about effective psychosocial treatment for ADHD?
AB  - Discussed the initial findings from the recently published, National Institute of
      Mental Health-sponsored Multimodal Treatment Study (MTA) of attention deficit
      hyperactivity disorder (ADHD). These findings can be summarized as follows:
      Medical management alone was found to be significantly more effective for the
      core symptoms of ADHD as compared to behavioral treatment alone and routine
      (community) care, and behavioral treatment did not significantly improve outcome
      when combined with medical treatment. In discussing these findings, it is
      important to be explicit about the research questions the study was and was not
      designed to answer. The MTA study provided useful information regarding the
      question, "Does a very intensive form of behavioral treatment deliver greater
      benefits than the less intensive forms of behavioral treatment investigated in
      prior studies?" but little insight on the question, "What type of treatment by
      what type of therapist is most effective in dealing with what specific problems
      among specific children with ADHD?" It is suggested that the clearest finding
      from the MTA study is that the effectiveness of psychosocial intervention for
      ADHD hinges on the degree to which a broad range of treatment ingredients are
      considered, carefully selected, matched, and tailored to the individual needs of
      each child with the disorder, and implemented and monitored over the long term.

PMID- 11294070
TI  - Tailored psychosocial treatments for ADHD: the search for a good fit.
AB  - Commented on the article "What Does the MTA Study Tell Us About Effective
      Psychosocial Treatment for ADHD?" by Greene and Ablon (this issue). In this
      article, these authors note that the Multimodal Treatment Study (MTA) did not
      focus on or provide information about how to match treatment to the needs of the
      individual child. They contend that cognitive-behavioral treatment (CBT), which
      was not included in the MTA, can facilitate treatment tailoring if delivered
      appropriately. The authors offer several suggestions regarding how CBT can be
      structured to meet the needs of each child. This commentary points out that the
      MTA included psychosocial treatments with established rather than potential
      efficacy. Systematic studies are needed to determine whether the suggestions
      offered by Greene and Ablon have clinical utility. Matching treatment to the
      needs of individual patients remains the overarching goal of those interested in
      idiographic approaches to treatment. However, efforts to inform on treatment
      tailoring involve complex design and needs assessment methodologies. Several
      suggestions are offered regarding the technology of treatment tailoring. These
      include the use of goal attainment scaling to identify and evaluate
      individualized outcome measures and the use of hybrid efficacy-effectiveness
      designs to assess the impact of treatment preference on outcome.

PMID- 11294071
TI  - Psychosocial treatment issues in the MTA: a reply to Greene and Ablon.
AB  - Discussed several of Greene and Ablon's (this issue) key points in their article
      about the Multimodal Treatment Study (MTA) of Children with Attention Deficit
      Hyperactivity Disorder (ADHD). In particular, the following issues are addressed:
      (a) whether the medication management and behavioral arms of the MTA
      individualized treatment to comparable degrees; (b) whether cognitive-behavioral
      interventions were incorporated to an adequate extent; (c) whether core ADHD
      symptoms were overemphasized relative to other functional domains, both as
      treatment targets and outcome measures; and (d) whether parent and teacher
      characteristics warranted more emphasis than they were given. These issues are
      discussed and an attempt is made to fit the MTA findings into the larger context
      of prior studies on treatment of childhood ADHD. A theme of this commentary is
      the concern that in the current age of biological emphasis in the field of ADHD
      research, social, family, and motivational processes may not get the attention
      they deserve.

PMID- 11294072
TI  - Comprehensive versus matched psychosocial treatment in the MTA study: conceptual
      and empirical issues.
AB  - Addressed some factual inaccuracies and presented alternative positions on key
      issues raised in the article by Greene and Ablon (this issue) on the question,
      "What does the Multimodal Treatment Study (MTA) tell us about effective
      psychosocial treatment for attention deficit hyperactivity disorder (ADHD)?" The
      Greene and Ablon critique does not present for the reader's consideration the
      full range of findings from the MTA study, notably those most relevant to
      psychosocial treatment, and articulates a theoretical position that effective
      treatment requires matching treatment to children's assessed needs, an approach
      not taken in the MTA study. In this article, I present the full range of findings
      from the MTA study related to psychosocial treatment effects, correct the
      misperceptions that exist about the study based on limited reviews such as Greene
      and Ablon's, and review the empirical and experimental design issues that
      produced the decision by the MTA investigative team to study the effects of
      intensive, comprehensive psychosocial treatment. I argue that the questions asked
      by the MTA study about psychosocial treatment were important, relevant, and were
      addressed well in the MTA study design.

PMID- 11294073
TI  - ADHD treatment in the 21st century: pushing the envelope.
AB  - Required for optimal intervention for attention deficit hyperactivity disorder
      (ADHD) is evidence-based matching of child, treatment, and situation. The
      landmark Multimodal Treatment Study (MTA) of Children with ADHD documented the
      superiority of pharmacotherapy for the vast majority of children with ADHD.
      Although this study could not address the problem of the match directly, it is
      generating important leads for research on the use of psychosocial strategies to
      enhance the scope and durability of treatment gains while decreasing the risks
      attendant upon long-term use of medication. Given the inherent distinctions
      between pharmacological and psychosocial treatments, conclusive answers to
      questions about comparative efficacy will continue to elude scientist
      practitioners. Needed next is research examining ways to improve outcomes beyond
      the effects of medication, using systematically tailored and sequenced
      psychosocial approaches and exploring new treatment targets, agents, and
      modalities. To illustrate, some emerging findings from an ongoing experience
      sampling study and implications for online therapy are discussed.

PMID- 11294074
TI  - Pivotal areas in intervention for autism.
AB  - Discusses several core pivotal areas that appear to be influential in
      intervention for autism. Literature and outcome data are reviewed with respect to
      several core areas that appear to be particularly helpful in intervention for
      autism, including improving motivation, responsivity to multiple cues, self
      management, and self-initiation of social interactions. A conceptual framework is
      described, and outcome data are reviewed suggesting that when children with
      autism are motivated to initiate complex social interactions, it may reverse a
      cycle of impairment, resulting in exceptionally favorable intervention outcomes
      for many children. Because the peripheral features of autism can be numerous and
      extensive, the concept of intervention for pivotal areas of functioning may be
      critical if children are to be habilitated in a time- and cost-efficient manner.

PMID- 11294075
TI  - Bridging theory and practice: conceptual understanding of treatments for children
      with attention deficit hyperactivity disorder (ADHD), obsessive-compulsive
      disorder (OCD), autism, and depression.
AB  - Serves as an introduction to a special edition of the journal on bridging theory
      and clinical practice for childhood disorders. Issues concerning the current
      trend of developing and evaluating new treatments devoid of a theoretical
      perspective are discussed. A conceptual model of child psychopathology is
      presented to illustrate the relevance and interplay between theory and the design
      and evaluation of treatments with particular emphasis on the selection and
      measurement of target behaviors. The means by which theory and empirical evidence
      interact and their relevance to understanding particular childhood disorders are
      discussed and emphasize the need for theoretical and conceptual models that
      describe the linkages among hypothesized brain substrates, cognitive function,
      behavior, and the environment to augment the development of potent biological and
      psychological interventions.

PMID- 11294076
TI  - Depression in youth: psychosocial interventions.
AB  - Witnessed over the past 20 years are major advances in knowledge regarding
      depression in children and adolescents. Although additional research is needed,
      clinicians can now turn to treatment strategies with demonstrated efficacy. In
      this article we review the literature on psychosocial interventions for
      depression in youth and offer a working model to guide the treatment of depressed
      youth. We begin with a brief overview of the model, followed by a review of the
      treatment efficacy and prevention literatures. We offer some caveats that impact
      the ability to move from this treatment literature to the real world of clinical
      practice. We conclude by considering how extant research can inform treatment
      decisions and highlight critical questions that need to be addressed through
      future research.

PMID- 11294077
TI  - A conceptual model of child psychopathology: implications for understanding
      attention deficit hyperactivity disorder and treatment efficacy.
AB  - Highlights the desirability of using a theoretical framework for guiding the
      design and evaluation of therapeutic interventions for children with attention
      deficit hyperactivity disorder (ADHD). A general conceptual model is introduced
      and used to evaluate ADHD treatment outcome research. Treatments designed to
      target the substrate level (pharmacological interventions) result in broad,
      robust improvement in both core and peripheral areas of functioning. Those
      targeting hypothesized core features of the disorder (i.e., attention,
      impulsivity-hyperactivity) produce corresponding improvement in core and
      peripheral outcome measures with the exception of studies employing cognitive
      behavior therapy. Those targeting peripheral features of the disorder effect
      change only in corresponding peripheral areas of functioning. Implications for
      clinical practice are discussed, and an alternative conceptual model of ADHD is
      introduced and compared with existing models.

PMID- 11294078
TI  - Bridging the enormous gaps of theory with therapy research and practice.
AB  - Convey remarkable advances in therapy outcome research and exemplify how leading
      investigators connect interventions to conceptual views about therapy. These
      comments focus on the distinction between broad conceptual views and theory about
      therapeutic change processes. Although there are explanations of why a treatment
      focus seems reasonable, there is very little testable theory or tests of theory
      in therapy research. The role, importance, and paucity of theory in child and
      adolescent psychotherapy research is described, underscored, and lamented,
      respectively, in these comments. Recommendations are made to move toward the goal
      of this series, namely, to bridge the gap of theory and clinical practice but
      also the gap of theory and therapy research.

PMID- 11294079
TI  - Pharmacological treatment of childhood obsessive-compulsive disorder: from theory
      to practice.
AB  - Discusses pharmacological treatment of childhood obsessive-compulsive disorder
      (OCD), chronic and underrecognized psychiatric condition that affects up to 2% to
      3% of children and adolescents. Research in OCD in children, including
      neuropharmacology, brain imaging, genetics, and clinical phenomenology, informs
      current views of OCD pathophysiology. Contemporary research supports the notion
      of a dysregulation in serotonin subsystems in the central nervous system, with
      target areas of dysfunction including basal ganglia and orbitofrontal cortex.
      Pharmacotherapy, along with cognitive-behavioral approaches, constitutes the
      indicated treatment for childhood OCD. Pharmacological treatment is best guided
      by a phenomenological understanding of the type of obsessions and compulsions,
      the intensity and frequency of their presentation with attention to behavioral
      reinforcements, and psychosocial factors that affect the course of the disease.
      Serotonin-enhancing agents, such as fluoxetine, fluvoxamine, paroxetine, and
      sertraline and citalopram (SSRIs) are first-line pharmacological agents, whereas
      refractory symptoms can be treated by augmentation with neuroleptics or other
      agents. Clomipramine is as effective as the SSRIs but its use may be accompanied
      by increased side effects. Genetic factors probably influence susceptibility to
      OCD as well as response to treatment, and the elucidation of these and other risk
      factors will be important elements in the future understanding and treatment of
      this disorder.

PMID- 11294080
TI  - Cognitive-behavioral psychotherapy for pediatric obsessive-compulsive disorder.
AB  - Discusses the cognitive-behavioral psychotherapy for pediatric obsessive
      compulsive disorder (OCD). Over the past 15 years, cognitive-behavioral
      psychotherapy has emerged as the psychosocial treatment of choice for OCD across
      lifespan. Unlike other psychotherapies that have been applied usually
      unsuccessfully to OCD, cognitive-behavioral treatment (CBT) presents a logically
      consistent and compelling relationship between the disorder, the treatment, and
      the specified outcome. Nevertheless, despite a consensus that CBT is usually
      helpful, clinicians routinely complain that patients will not comply with
      behavioral treatments and parents routinely complain that clinicians are poorly
      trained in CBT, with the result that many if not most children and adolescents
      are denied access to effective psychosocial treatment. This unfortunate situation
      may be avoidable, given an increased understanding regarding the implementation
      of CBT in children and adolescents with OCD. To this end, we review the
      principles and the practical aspects of the cognitive-behavioral treatment of OCD
      in youth, move on to discuss empirical studies supporting the use of CBT in the
      pediatric age group, and conclude by discussing directions for future research.

PMID- 11294081
TI  - Pharmacological interventions in autism: theoretical and practical issues.
AB  - Focused on issues of drug treatment in relation to autism. Pharmacological
      treatment studies in autism are complicated by various factors including a
      tremendous range of syndrome expression, a lack of robust animal models of the
      disorder, and various methodological problems. Theories have tended to follow
      treatments, and various neurochemical systems have been the focus of study.
      Neurochemical systems potentially implicated include those involving dopamine,
      norepinephrine, serotonin, and neuropeptides. The dopaminergic system has been
      the most extensively studied. Treatments developed are effective relative to
      certain disabling symptoms but "core" problems (e.g., in social relatedness and
      communication) appear less responsive to medications. The development of new
      approaches to assessment, including integration of behavioral and pharmacological
      approaches, is an important research priority.

PMID- 11294082
TI  - Childhood depression: pharmacological therapy/treatment (pharmacotherapy of
      childhood depression).
AB  - Critiqued the published double-blind, placebo-controlled studies of
      antidepressant pharmacotherapy in child and adolescent major depressive disorder
      to assess their overall efficacy. The pharmacological mechanism of antidepressant
      action also was discussed. At best, antidepressant treatment for depressed youths
      is only modestly effective. In particular, the tricyclic antidepressants are not
      superior to placebo; however, early evidence with the selective serotonin
      reuptake inhibitors is more encouraging. The theoretical basis for this response
      pattern is discussed from a methodological perspective, from a neurodevelopmental
      status, and from a biological viewpoint. Study modifications are suggested which
      could improve some of the methodological limitations apparent in previous
      clinical drug trials.

PMID- 11294083
TI  - Stimulant effects in attention deficit hyperactivity disorder: theoretical and
      empirical issues.
AB  - The explanatory utility of a theory or model of ADHD or any disorder depends
      fundamentally on its capacity to address issues of causality. What causes a
      particular child to develop ADHD? What mechanisms are responsible for temporal
      and setting-related variations in symptom severity, and how are these mechanisms
      affected by pharmacological intervention? And, what processes determine whether
      gains in one domain will propagate across one or more others? It should be
      evident from the foregoing discussion that comprehensive answers to such
      questions are most likely to emerge through implementation of research strategies
      that (a) integrate biological and psychological levels of explanation, (b) permit
      analysis of causal hypotheses, and (c) address mechanisms involved in both
      etiology and mediation of treatment response. Although extant neurobiological
      studies of ADHD are as compelling as they are exciting, they are limited by a
      troubling reductionistic emphasis. The predominant animal models focus on a
      narrow range of behaviors that are presumed to be central to ADHD because of the
      topographic similarity they bear to those represented by the diagnostic criteria
      incorporated into the diagnostic nomenclature. These models would become
      increasingly valuable to the extent that future research examined the extent to
      which ecologically relevant behaviors (e.g., social behavior) are compromised in
      the animal strains and whether the observed compromises are parallel to the
      correlates of ADHD observed in humans. Similarly, human molecular genetic studies
      have provided a glimpse into the possible role that genes related to dopaminergic
      neurotransmission may play in the etiology of ADHD. Yet, the features of ADHD
      have been conceptualized in these investigations as a unitary collection of
      characteristics, and this has precluded analysis of what specific syndromal
      feature (if any single one) is affected by the implicated genes. It is intriguing
      to speculate whether varying combinations of genes governing properties of DA
      receptors and reuptake molecules are associated with different patterns of
      symptom severity or responses to stimulant medications. As testing procedures for
      determining genotypes with respect to these features become more affordable and
      available, it should become increasingly feasible to examine such issues
      empirically. Research on the utility of stimulant drugs as a treatment for ADHD
      also has yielded useful information. Although the effects of MPH are of short
      duration, the breadth of their impact is impressive. The clinical effectiveness
      of these medications is no longer in doubt, and patterns of relations among
      outcome measures represent a potentially fruitful target of scientific inquiry.
      Finally, data supporting a neurobiological substrate for ADHD, evidence
      indicating that task and setting variables moderate the expression of the
      syndrome's diagnostic features (see Barkley, 1998, for a review), and the causal
      emphasis of the conceptual model with which the discussion began collectively
      argue for a diathesis-stress conception of the syndrome. And, as foregoing
      comments make clear, task and setting variables and the mechanisms through which
      they influence symptom expression are as important to the phenomenon as are
      neurobiological predisposing causes. This has significant implications for
      assessment strategies employed in diagnosis and evaluation of treatment-outcome.
      Specifically, it suggests that theory-based experimental manipulations of task
      and setting variables designed to impose challenge on hypothesized core features
      of the disorder are more likely to yield insights into the causal mechanisms
      governing behavioral organization in affected children than strategies
      emphasizing static identification of diagnostic correlates. It is hoped that such
      an approach will accelerate the discovery of increasingly effective assessment
      and intervention strategies.

PMID- 11294084
TI  - Gonadotroph cell pituitary adenomas in males.
AB  - BACKGROUND: Considered exceptional in the past, gonadotroph cell pituitary
      adenomas account for 3.5-6.4% of total surgically excised pituitary adenomas when
      examined with immunospecific staining. The aim of this study was to describe the
      clinical, hormonal, radiological and immunohistochemical features, the management
      and the follow-up of our patients with gonadotroph adenoma. METHODS: In this
      retrospective study we describe 14 male subjects aged 19-70 yrs affected by
      gonadotroph cell pituitary adenomas; the patients were studied by hormonal,
      radiological and immunohistochemical investigations and followed up for 3-13 yrs
      by ambulatory and/or hospitalized care. RESULTS: Visual impairment and/or
      decreased libido and erectile dysfunction were the symptoms at presentation.
      Increased serum gonadotropin concentrations were shown in 3 patients. Reduced
      levels of testosterone were present in 9 patients, and normal in the remainder.
      At diagnosis all patients had pituitary macroadenomas, with wide extrasellar
      extension in 12. All patients underwent trans-sphenoidal surgery and
      immunohistochemical staining of surgically excised specimens showed the presence
      of gonadotroph and alpha-subunit cells in all pituitary adenomas. After surgery 3
      patients had clear radiological evidence of normal pituitary; in the others a
      doubtful MRI picture or a residual adenomatous tissue were present. In the
      patients who did not undergo radiotherapy immediately after surgery, a regrowth
      of tumoral tissue was shown in 1-10 yrs. CONCLUSIONS: We stress the importance of
      a close follow-up of patients with gonadotroph adenomas after surgery, and we
      raise the question of whether radiotherapy may be useful for avoiding any further
      adenomatous regrowth.

PMID- 11294085
TI  - One-year follow-up of Graves' disease treatment by four different protocols of
      radioiodine administration.
AB  - BACKGROUND: Studies have been performed in order to assess a treatment with 131I
      able to induce a consistent improvement in Graves' hyperthyroidism. METHODS: 
      EXPERIMENTAL DESIGN: For this purpose, four different protocols based on four
      different doses of radioiodine have been tested in Graves' disease patients.
      Patients never submitted previously to antithyroid drug treatment were given 1
      mCi/10 gm of the estimated thyroid weight (group I; n = 50). Group II (n = 48)
      included patients not previously treated with antithyroid drugs and who were
      given doses of iodine based on a formula taking into account the rate of thyroid
      iodine uptake, i.e. 131I dose = microCi/gm of the estimated thyroid weight x
      100/24 hrs 131I uptake (%). Patients previously submitted to antithyroid drug
      therapy were treated with radioiodine whose dose was calculated according to the
      formula reported above, but the dose was increased in order to overcome the
      possible resistance of this kind of patients to the effect of 131I. One group
      (group III; n = 24) received the calculated dose plus 1 microCi/gm of the
      estimated thyroid weight. Finally, group IV (n = 27) received the calculated dose
      plus 0.25 microCi/gm of the estimated thyroid weight. RESULTS: The analysis of
      the patients one year later demonstrated that groups I and II presented the
      higher percent of euthyroid patients (60% and 58%, respectively) followed by
      group IV (37%) and group III (29.2%). The percent of patients still exhibiting
      hyperthyroidism was 28% in group I, 26% in group IV, 12.5% in group III and 8.3%
      in group II. The highest number of hypothyroid patients was present in group III
      (58.3%) followed by group IV (37%), group II (33.3%) and group I (12%).
      CONCLUSIONS: The data here presented suggest that protocols I and II based on
      relatively low doses of radioiodine are rather effective in reducing Graves'
      hyperthyroidism in patients not submitted previously to antithyroid drug therapy.
      The most satisfactory therapy seems that utilized in protocol II, that in front
      of a fair amount of euthyroid patients (58.3%) presents a very low number of
      subjects still hyperthyroid (8.3%). However, the number of patients who became
      hypothyroid (33.3%) as a consequence of the therapy was too high. Hopefully, a
      better design of the protocol will reduce this figure. The high incidence of
      hyperthyroidism observed in groups III and IV submitted to a therapy with 131I
      doses consistently higher than those utilized in groups I and II seems to confirm
      the hypothesis that hyperthyroid subjects submitted to a therapy with antithyroid
      drugs become rather resistant to a radioiodine treatment.

PMID- 11294086
TI  - Diffuse idiopathic skeletal hyperostosis in diabetes mellitus, impaired glucose
      tolerance and obesity.
AB  - BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is a rheumatic
      disease characterized by a significant association with metabolic alterations,
      such as an impaired lipidic profile. METHODS: One-hundred-thirty consecutive
      patients and 40 normal subjects were studied. The patients were affected by type
      1 and type 2 diabetes mellitus, impaired glucose tolerance and obesity. The
      diagnosis of DISH was performed by clinical examination and X-ray study of the
      thoracolumbar spine. The determination of total cholesterol, triglycerides, HLD
      cholesterol and LDL-cholesterol was realized by routine biochemical methods; an
      oral glucose tolerance test was performed in order to determine the levels of C
      peptide and blood glucose. RESULTS: We demonstrate a high incidence of the
      disease in a cohort of patients affected by overt and non-overt diabetes mellitus
      (T1DM and T2DM) as well as in obese subjects and a correlation between this
      disorder and hypertryglyceridemia (T1DM, obese-T2DM and obese patients), hypo-HDL
      cholesterolemia (obese-T2DM, non-obese-T2DM and obese patients) and hyper-LDL
      cholesterolemia (obese patients). In obese-T2DM patients, as well as in obese
      patients, we observed 40% of DISH, in non obese-T2DM patients the presence of
      DISH was 30%, while in T1DM patients and impaired glucose tolerance 26.6% and
      22.2, respectively. However, a correlation between DISH and the relative
      hyperinsulinemia in obese patients during an oral glucose tolerance test is not
      documented. CONCLUSIONS: Our study confirms the prevalence of DISH in diabetes
      mellitus and obesity, the association with an impaired lipidic profile and the
      low percentage of symptomatic patients.

PMID- 11294087
TI  - Preservation of myocardial functions by pentoxyphylline cardioplegia during and
      after cardiopulmonary bypass.
AB  - BACKGROUND: The aim of the presented study was to evaluate the preservation
      effect of the pentoxyphylline-blood cardioplegia on myocardial functions during
      and after the cardiopulmonary bypass in an experimental dog model. METHODS:
      Central hemodynamics and metabolic variables such as creatine phosphokinase,
      myocardial oxygen extraction and myocardial lactate extraction were obtained
      during and following 4 hours after the cardiopulmonary bypass after the baseline
      scores were recorded. Twelve mongrel dogs were divided into two equal groups. The
      first group of animals served as controls. The second group of animals was
      treated with pentoxyphylline cardioplegia that was added to each blood
      cardioplegia as 15 mg/100 ml. RESULTS: After bypass, the hemodynamic parameters
      were better in the pentoxyphylline group. Cardiac index fell in all animals, but
      it was significantly less in the control group. Pulmonary capillary wedge
      pressure was lower in the pentoxyphylline group as an index of better
      preservation of ventricular filling pressure. CPK-MB was significantly higher in
      the control group both at 2 and 4 hours after the bypass. It was 79 +/- 13 iu/L
      in the control group and 41 +/- 9 iu/L in the pentoxyphylline group 4 hours after
      cardiopulmonary bypass. MLE was also higher both on bypass and following bypass
      in the control group. CONCLUSIONS: In conclusion, pentoxyphylline usage may
      reduce the risks of ischemic-reperfusion injury during and following
      cardiopulmonary bypass and aortic cross-clamping. It can be an administered drug
      during cardioplegia.

PMID- 11294088
TI  - Myotonic dystrophy and cardiac disorders.
AB  - Myotonic dystrophy (MD) is a multisystem disease affecting numerous organs and
      systems. Cardiac involvement is frequent. Sudden death, due to fatal cardiac
      rhythm and conduction disturbances occurs in 30% of patients with MD. The aim of
      this study was to assess the possibilities and methods of early detection of
      myocardial and conduction system disturbances. ECG, 24-hr Holter monitoring,
      echocardiography and electrophysiologic studies of the conduction system
      (electrophysiologic study) were carried out in 45 patients. Analysis of late
      ventricular potentials was done in 36 patients. Genetic studies revealed
      multiplication of CTG triplets in all patients. Cardiological abnormalities were
      detected in 89% of our patients. Disturbances of intraventricular conduction with
      prolongation of HV interval were most frequent (72%). Electrophysiologic study
      was the most sensitive method for detecting heart involvement in MD (positive
      findings in 87% patients). Abnormal findings were also discovered by Holter
      monitoring (64%), ECG (58%), analysis of late ventricular potentials (55%) and by
      echocardiography in 46% patients. The results of this study indicate a high rate
      of cardiac involvement in MD.

PMID- 11294089
TI  - Impaired cutaneous cell-mediated immunity in newly diagnosed rheumatoid
      arthritis.
AB  - BACKGROUND: Rheumatoid arthritis is characterized by an impaired immune response
      and a defective cutaneous cell-mediated immunity has been reported. This study
      was realised in order to determine the characteristics of cutaneous cell-mediated
      immunity in patients affected by recent-onset and untreated rheumatoid arthritis.
      METHODS: Forty-eight patients affected by newly diagnosed rheumatoid arthritis
      were studied by skin testing with seven common recall antigens. The skin tests
      were performed before the administration of disease modifying anti-rheumatic
      drugs (methotrexate, cyclosporine-A, hydroxychloroquine) and were repeated after
      four months of therapy. RESULTS: 43.75% of the RA patients (21 out of 48) were
      defined as anergic compared with 2% of the normal control subjects and the rate
      of depression of cutaneous cell-mediated immunity was not related either with the
      markers of disease activity or with the clinical assessment. The impaired
      cutaneous cell-mediated immunity shows a slight improvement after methotrexate
      therapy, while cyclosporine-A and hydroxychloroquine were not able to achieve the
      same result. CONCLUSIONS: Rheumatoid arthritis shows a defective cutaneous cell
      mediated immunity when the patients are studied in the early phase of the disease
      and before a second-line of therapy with disease modifying anti-rheumatic drugs.
      The anergy does not correlate either with the disease activity or with the short
      term response to treatment. The prognostic significance of these data remains
      uncertain.

PMID- 11294090
TI  - Neurophysiologic exploration: a reliable tool in HIV-1 encephalopathy diagnosis
      in children.
AB  - BACKGROUND: HIV-1 related encephalopathy has a bad prognostic meaning in the
      course of AIDS disease, but the early association of different drugs can modify
      its course. For this reason it is very important to recognize CNS involvement as
      soon as possible. As shown in the literature, at least in adult studies, EEG and
      Evoked Potentials (EP) are good tools in evaluating CNS alterations. In children
      data are rare. METHODS: A ten-year prospective study of 44 infected children out
      of 142 born from HIV-1 positive mothers has been done. The children have been
      submitted to EEG recording every six months in the first 18 months of life and
      then every year, to multimodal EP every six months. A total of 357 EEG, 47 P-VEP,
      62 F-VEP and 98 BAEP have been performed. RESULTS: EEG: we found no pathologic
      results in patients belonging to category A; results were pathologic in 17.7% in
      category B, in 47.7% in C and in 77% of encephalopathic patients. It seems that
      EEG alterations are parallel to disease progression, with a relative risk of
      developing encephalopathy (R.R. = 1.15) and of death (R.R. = 2.33) for patients
      belonging to category C. We obtained a statistically significant lengthening in
      BAEP interpeak latency of left ear in all groups. For patients in category C the
      risk of developing encephalopathy is statistically significant (p = 0.045; R.R. =
      6.75) and risk of death is high (R.R. = 4). CONCLUSIONS: Neurophysiologic exams
      are a reliable tool for the diagnosis of encephalopathy, in addition to clinical
      evidence.

PMID- 11294091
TI  - Blood zinc, copper and magnesium in aging. A study in healthy home-living
      elderly.
AB  - BACKGROUND: Blood concentrations of copper, zinc and magnesium were determined in
      healthy elderly to assess whether aging interferes with mineral and micronutrient
      status. METHODS:  EXPERIMENTAL DESIGN: case series. SETTING: Internal Medicine
      and Geriatrics ambulatories in a University Hospital in Pisa, a city of Central
      Italy. PARTICIPANTS: 143 healthy outpatients of both sexes, who underwent a
      cardiological examination. INTERVENTION: no treatment and intervention were
      performed. MEASURES: copper (Cu), zinc (Zn) and magnesium--both intraerythrocytic
      (iMg) and extracellular (eMg)--were measured. RESULTS: The concentrations of Cu
      and eMg were found significantly higher in the elderly: Cu 117.5 +/- 17.0
      micrograms/dl in the elderly vs 102.5 +/- 19.6 micrograms/dl in the younger (p <
      0.001); eMg 1.8 +/- 0.2 in the elderly vs 1.7 +/- 0.2 mEq/l in the younger (p <
      0.05). On the other hand, the levels of Zn and iMg did not differ in the two
      groups: Zn 113.3 +/- 14.9 micrograms/dl in the elderly vs 118.0 +/- 17.3
      micrograms/dl in the younger, p = n.s.; iMg 4.3 +/- 0.4 mEq/l in the elderly vs
      4.2 +/- 0.4 mEq/l in the younger, p = n.s. No correlation was found between age
      and single elements. CONCLUSIONS: These results suggest that the healthy free
      living elderly have an adequate mineral intake. Nutrient supplements may by
      useful in the elderly with chronic diseases, comorbidities, and polypharmacy to
      prevent further age dysfunctions.

PMID- 11294092
TI  - Subacute pancreatic necrosis.
AB  - Acute necrotising pancreatitis is the most serious form of acute pancreatitis and
      accounts for the majority of complications. Treatment of patients with pancreatic
      necrosis is still controversial. There is a well-established definition for acute
      pancreatitis and consequent pancreatic fluid collections. However, it has been
      identified a group of patients who represent a separate entity and whose
      collections may prompt additional change from the definition of acute
      pancreatitis. Imaging investigations in these patients have well defined subacute
      collections that evolve from severe acute necrotising pancreatitis involving
      greater than 30% of the gland. Although these collections are not completely
      liquefied, they do not meet criteria for pseudocysts, however, at the same time,
      they are morphologically different from acute pancreatic necrosis seen during
      initial presentation of acute pancreatitis. It has been used to call "subacute"
      these collections of necrotic pancreatic tissue or "subacute pancreatic
      necrosis". The purpose of this review is to summarise the subacute collections of
      necrotic pancreatic tissue and its complications, discussing treatment options of
      the complex pancreatic and peripancreatic collections found in these patients,
      focusing on the management of subacute pancreatic necrosis.

PMID- 11294093
TI  - Management strategies in resection for carcinoma of the hepatic duct confluence:
      how to increase the resectability rate. Our experience and literature review.
AB  - The resectability rate of hilar bile duct carcinoma is reported to be variable
      and to inversely correlate with the size of the associated liver resection. In an
      attempt to reduce the risk of postoperative liver failure, the induction of a
      hypertrophy of remnant liver by preoperative portal vein embolization (PVE) has
      been proposed. We hereby analyse the results and the technical aspects of this
      procedure along with our personal experience.

PMID- 11294094
TI  - Thyrotoxic periodic paralysis in a Caucasian man in treatment for Graves'
      disease.
AB  - Thyrotoxic periodic paralysis (TPP) is the main secondary form of hypokalemic
      periodic paralysis and is mostly associated with Graves' disease. Initially
      diagnosed in Asian countries, TPP has been sporadically reported in different
      populations of the Western World. Increased Na+/K(+)-ATPase activity seems to be
      responsible for the marked hypokalemia observed during the transient paralysis
      attacks. We report on a 35-year-old Italian man without history of hypokalemic
      periodic paralysis and hyperthyroidism, in treatment for Graves' disease, who
      suffered episodes of flaccid paralysis even with normal thyroid hormone levels.
      An insulin-glucose provocation test confirmed our diagnosis. Oral and parenteral
      potassium reverse the symptoms. Monitoring of thyroid function is also important
      to prevent further attacks.

PMID- 11294095
TI  - Arterial thoracic outlet syndrome with embolic cerebral infarction. Report of a
      case.
AB  - Cerebral embolism is a very rare but recognized manifestation of arterial
      complications of thoracic outlet syndrome, and is associated with retrograde
      embolization in the cerebral arteries. We herein report a case of embolic brain
      infarction due to arterial thoracic outlet syndrome while discussing the
      etiology, diagnosis, and surgery.

PMID- 11294096
TI  - Screening for coeliac disease in women with recurrent spontaneous abortion sine
      causa.

PMID- 11294097
TI  - [Accreditation of hospital and local health unit management].
AB  - The authors state that an authoritative Clinical Director of a General Hospital,
      an active and efficient leadership of a Public Health District or Local Health
      Unit are very important to allow Italian Health Care System to cope with present
      and future challenges. The medical management must be professionally specialistic
      and be object of accreditation. This must be the target of professional training
      so that Medical Management Staff can have the necessary competence to carry
      complex management activities correctly out.

PMID- 11294098
TI  - [Autoantibodies in chronic hepatitis C. Markers of autoimmunity or non-specific
      events?].
AB  - In the light of the high prevalence of non organ-specific autoantibodies in
      chronic hepatitis C, the possibility that such a finding may represent the
      consequence of a viral, autoimmune or overlapping disease should be considered,
      which may in turn require a different therapeutical approach. It is known,
      anyway, that the diagnosis of autoimmune hepatitis is based on a set of
      epidemiological, clinical, biochemical, histological criteria and autoantibody
      pattern. In 113 cases of chronic hepatitis with HCV infection, we determined the
      presence of non organ-specific autoantibodies [anti-nuclear (ANA), anti-smooth
      muscle (SMA), anti-liver-kidney microsomal antibodies (LKM), anti-mithocondrial
      antibodies (AMA)] and described the epidemiological, clinical, biochemical,
      histological characteristics and therapeutic response to interferon. 40 patients
      (35%) exhibited non organ-specific autoantibodies: 25 patients were SMA positive
      (Vasal pattern), 4 ANA positive (Speckled pattern), 7 ANA (Speckled pattern) +
      SMA (Vasal pattern) positive and 4 LKM positive. All subjects with HCV infection
      and autoantibodies did not display additional criterias of autoimmunity,
      including the same outcome to interferon therapy when compared to HCV positive
      patients without autoantibodies. The failure to determine clinical features,
      associated to autoimmunity in HCV positive patients with autoantibodies, suggests
      that autoantibody occurrence may represent a fortuitous event during the course
      of HCV infection.

PMID- 11294100
TI  - [Antiphospholipid antibody syndrome].
AB  - Antiphospholipid antibodies (aPL) are an eterogeneous group of immunoglobulins,
      that include lupus anticoagulant and anticardiolipin antibodies. Patients with
      aPL are at high risk of venous and arterial thrombosis, thrombocytopenia and
      recurrent fetal loss. Antiphospholipid antibodies should be suspected in case of
      unexplained thrombophilia and prolongation of coagulation assays (aPTT); infact
      although such antibodies present an anticoagulant effect in vitro, in vivo the
      interfere with physiological anticoagulant reactions and may have a procoagulant
      effect. This paper deals with a case report characterized by a poor
      sintomatology, a short bleeding, but a spread of abnormal laboratoristic findings
      that give us the opportunity to investigate an uncommon syndrome.

PMID- 11294099
TI  - [Diagnosis of Helicobacter pylori infections using isotope-selective non
      dispersive infrared spectrometry with 13C-urea breath test].
AB  - OBJECTIVE: The 13C-Urea Breath Test (13C-UBT) is a non-invasive simple and
      reliable test for the diagnosis of Helicobacter pylori infection. Widespread use
      of the test is limited by the high cost of isotope-ratio mass-spectrometry that
      is required for analysis of the breath samples. The aim of our study was: 1)
      evaluate the accuracy of a simple optical method called isotope-selective non
      dispersive infrared spectrometry (NDIRS), which is designed to measure
      13CO2/12CO2 ratio; 2) evaluate the possibility to reduce timing of breath samples
      collection after 13C-urea ingestion. METHODS: 13C-UBT and gastroscopy were
      performed in one hundred patients (mean age: 51 years; range: 18-81 years; M/F:
      48/52) after overnight fasting. None had taken antibiotics, proton pump inhibitor
      or bismuth-containing preparations for at least four weeks. Two biopsies from the
      antrum and two from the body of the stomach were obtained from each patient to
      investigate the Helicobacter pylori status. Breath samples were collected from
      each patient in aluminised plastic bags with a volume of 1200 ml, before and 10,
      20 and 30 minutes after ingestion of 75 mg 13C-urea dissolved in 200 ml of orange
      juice. A value of "Delta-Over-Baseline" higher than 4@1000 was considered
      positive. The operators of each device were unaware of Helicobacter pylori
      status. RESULTS: 54/55 patients resulted positive on 13C-UBT in respect of
      immunohistochemistry. 44/45 patients resulted negative on 13C-UBT in respect of
      immunohistochemistry. The sensibility resulted 98.1%, specificity 97.7%. No
      significant difference between sample collection at 10, 20 or 30 minutes after
      ingestion of 13C-urea was found (Chi square: p: n.s.). DISCUSSION: This study
      shows that the diagnostic accuracy of infrared spectroscopy is excellent and
      comparable with data of other authors about conventional isotope-ratio mass
      spectrometry. No significant difference between sample collection at 10, 20 or 30
      minutes after ingestion of 13C-urea was found (Chi square: p: n.s.). Timing of
      sample collection may be reduced from 30 to 10 minutes with the purpose of cut
      down more the costs for this test.

PMID- 11294101
TI  - [Bacteremia in tonsillectomy: Sluder's technique versus dissection. Preliminary
      results].
AB  - Fifty-one patients undergoing elective tonsillectomy for recurrent acute
      tonsillitis, 21 by dissection tonsillectomy (41%), and 30 guillotine
      tonsillectomy (59%). Positive post-operative blood cultures were obtained in 22
      patients (43%), but only 4 in the dissection group (19%) and in 18 of the
      guillotine group (60%). Streptococci (21.5%) and Staphylococci (9.8%) are the
      commonest organisms cultured. This data are suggestive for the necessity of an
      antibiotic prophylaxis before tonsillectomy.

PMID- 11294102
TI  - [Hypopituitarism in the elderly at an internal medicine department].
AB  - We describe three cases of hypopituitarism with empty sella in elderly patients. 
      Hypopituitarism in geriatric population is not uncommon, but is oftern
      underestimated and confused with more frequent diseases.  It can sometimes
      determine severe clinical picture, above all for the consequences of
      adronocortical insufficiency. We emphasize that empty sella  is not always an
      asymptomatic radiological finding.

PMID- 11294103
TI  - [Integrated (surgical and hormonal) treatment of advanced prostatic carcinoma.
      Comment on the study and the interview with Edward M. Messing].

PMID- 11294104
TI  - [Update of the study on survival with early hormonal therapy associated with
      radiotherapy (EORTC 22863 Study) in patients with advanced prostatic cancer.
      Interview with Michel Bolla].

PMID- 11294105
TI  - [Hormonal therapy associated with radiotherapy of advanced carcinoma of the
      prostate. Comment on the study and interview with Michel Bolla].

PMID- 11294106
TI  - [Medical treatment of pulmonary neoplasms].
AB  - Over the past 20 years, the treatment of lung cancer has improved significantly:
      platinum-based chemotherapy represents the standard treatment in locally advanced
      and metastatic non-small cell lung cancer disease because of its impact on
      survival and quality of life. Adjuvant and neoadjuvant chemotherapy may also play
      an important role in the betterment of the outcome of earlier stages of disease.
      New drugs have become part of the therapeutic armamentarium in the treatment of
      advanced non-small-cell lung cancer. Gemcitabine, taxanes, irinotecan, and
      vinorelbine have been shown, alone or in combination with platinum derivatives,
      to interfere with the natural history of disease. As far as small cell lung
      cancer is concerned, the combination of chemotherapy (cisplatin and etoposide)
      and radiation therapy has yielded long term survivals in excess of 20%. The role
      of non-platinum combinations, particularly in the elderly and in patients with
      poor performance status as well as salvage therapy in patients relapsed after
      platinum treatment, will be the object of ongoing and future studies. Also the
      significance of newer agents, such as anti-angiogenesis factors and growth factor
      receptor inhibitors, used either alone or in combination with standard cytotoxic
      regimens, will have to be evaluated.

PMID- 11294107
TI  - [Structural arterial abnormalities in the offspring of subjects with premature
      myocardial infarction].
AB  - The offspring of patients with premature myocardial infarction are at increased
      risk for atherosclerosis and its clinical sequelae. High resolution B-mode
      ultrasonography is considered a reliable method for measuring intima-media
      thickness of common carotid arteries, a valuable marker of early atherosclerosis.
      Few recently published studies have evaluated the relationship between familial
      history of coronary artery disease and carotid intima-media thickness showing
      that anatomical arterial changes are detectable in subjects with such a history,
      independently from other well established coronary artery disease risk factors.
      These findings suggest that carotid intima-media thickness measurement, added to
      evaluation of classical coronary risk factors, may be useful to better identify
      high risk subjects.

PMID- 11294108
TI  - [Epidemics of bovine spongiform encephalopathy and new variant of Creutzfeldt
      Jakob disease in humans. Most recent findings on prion disease].
AB  - Prion diseases have been popularized by extensive media coverage of bovine
      spongiform encephalopathy (BSE) or "mad cow disease" epidemic, observed in Great
      Britain since 1986, and new variant Creutzfeldt-Jakob disease (nvCJD), reported
      for the first time in 1996. In contrast to the classical form of the disease,
      nvCJD affects younger patients, presents a relatively longer duration of illness
      and is caused by the same agent as BSE. Evidence from laboratory studies now
      strongly supports the hypothesis that new variant represents human form of animal
      disease, linked to exposure, probably through food, to bovine prions. Number of
      BSE reports in the United Kingdom began to decline in 1993, and has continuously
      decreased year by year since then, but a great worry spread in European countries
      in association with new BSE reported cases outside of the Great Britain, and
      increasing incidence of nvCJD. New epidemiological, clinical, histopathological
      and experimental data on prion diseases are reviewed, focusing our attention on
      the possible transmission of prion proteins from animals to humans.

PMID- 11294109
TI  - [Pruritus. Physiopathology, clinical features, and treatment].
AB  - Pruritus is a subjective disturbance that accompanies many dermatological,
      allergic and internal medicine disorders. It may well be the only symptom that
      leads a patient to consult a doctor. In situations of this kind, the cause of the
      complaint is very hard to determine and the tests employed often fail to give a
      clear-cut answer. This paper stresses the complexity of the hypotheses advanced
      to illustrate the pathogenesis of pruritus and reviews its many chemical
      mediators. An account is also given of the pathogenetic pointers that can be
      drawn from the conditions, including some within the compass of internal
      medicine, most commonly associated with pruritus and taken into consideration in
      the planning of individual treatment regimens.

PMID- 11294110
TI  - [Hepato-pulmonary syndrome and porto-pulmonary hypertension. Nosologic features
      and etiopathogenic considerations].
AB  - The liver controls pulmonary vascular tone by releasing vasoactive substances. In
      severe liver failure, the imbalance between vasodilator and vasoconstrictive
      mediators may lead to alteration of the respiratory function, called as
      hepatopulmonary syndrome (HPS, when a significant decrease of the vascular
      pulmonary resistance occurs, with development of intrapulmonary vascular
      dilatations) and portopulmonarv hypertension (PPH, when the vasoconstrictive
      prevalence, with an increase of the pulmonary vascular resistances). The clinical
      symptoms consist of various degree of dyspnea and hypoxemia. An overt "cor
      pulmonale" syndrome with right-side heart failure may be present in the most
      severe forms of PPH. The alteration of pulmonary vascularization may be diagnosed
      by means of pulmonary angiography, contrast-enhanced echocardiography and
      perfusion lung nuclear scanning of the lungs. Both clinical syndromes respond
      poorly to medical treatment, the unique therapeutical possibilities being
      represented by orthotopic liver transplantation (or combined heart-lung-liver or
      lung-liver transplantation in patients with severe PPH).

PMID- 11294111
TI  - [Microvascular decompression intervention in the treatment of trigeminal
      neuralgia].
AB  - The incidence of trigeminal neuralgia is about 5/10. Generally elderly people are
      affected by the so called "essential" form, although an early onset is not
      infrequent in secondary forms. The etiopathogenesis as well as the efficacy of
      different surgical treatments are still unclear because of the lack of animal
      sperimental models and of randomized controlled clinical studies. Nevertheless
      the hypothesis of a vascular conflict as the main etiologic factor is generally
      accepted. According both to our experience and to the literature data,
      microvascular decompression in the cerebello-pontine-angle appears to be the best
      clinical option presenting the most advantageous cost-benefit balance. The use of
      percutaneous lesive techniques, even if effective, should be limited in
      consideration of the risk of developing neuropathic disturbances, sometimes more
      difficult to treat than the original pain.

PMID- 11294112
TI  - [Medical progress, ethics, and euthanasia: the case of neonatal intensive care].
AB  - Failing to define what is meant by euthanasia often complicates the ethical
      debate, and exacerbates the conflict between supporters of different views. The
      scientific and technological progress of modern medicine may lead to difficult
      dilemmas when available treatment can only prolong the process of dying, or
      achieve survival at the expenses of severe residual disability. As an example,
      the case of neonatal intensive care is discussed on the basis of the results
      provided by an international research project (EURONIC) aimed at investigating
      end-of-life decision-making in several European countries.

PMID- 11294113
TI  - [Prospects of molecular pharmacology in oncology].
AB  - The evaluation of the precise mechanism of action of a new anticancer agent is a
      crucial step for a better utilization of drugs in cancer therapy. The increased
      knowledge of the molecular alterations present in different tumors, combined with
      the identification of the intracellular targets of a drug is the initial step for
      the possible, future molecular-oriented chemotherapy. It is in fact possible now
      to know if and how a given drug is able to interact with DNA and if the DNA
      sequence is a key factor in determining such interaction. Drugs are available
      with high sequence specificity of DNA interaction and these results, combined
      with the knowledge of the DNA sequences important for the regulation of gene
      expression, can help in identifying possible intracellular targets of the drugs.
      The recent introduction of the microarray technology has changed our approach to
      the study of drug effects on gene expression. In a single experiment is possible
      to identify changes in gene expression of plenty of genes and to have information
      on the alterations in the expression of gene families. These studies, combined to
      the effects on proteins involved in cell cycle control and in the induction of
      apoptosis, allow a better understanding of the interaction between drugs and
      cellular control mechanisms.

PMID- 11294114
TI  - [Is there a role for clinical medicine in the threshold of the third
      millennium?].
AB  - The technological advances of the last decades favoured remarkable successes in
      the study and the treatment of diseases. On the other hand, it risks to take the
      physician away from the interpersonal relationship with the patient. This kind of
      relation should be grounded, most of all, on hearing and dialogue, on the
      practice of observation, semeiologic interpretation and clinical reasoning, as
      well as on fixed parameters, laboratory tests and instrumental investigation. To
      reduce this kind of risk and to return the physician of the twenty-first century
      all the peculiarities of the bonus sanandi peritus, the author hopes that
      medicine is going to become a "medicine of the person" again: a medicine that
      will always prefer the therapeutical alliance and the clinical mode of diagnostic
      procedures.

PMID- 11294115
TI  - The effect of Rapid Induction Analgesia on subjective pain ratings and pain
      tolerance.
AB  - The effect of Rapid Induction Analgesia (RIA) on pain tolerance and ratings of
      mechanically induced pain in the pain-sensitized forearm was investigated in 58
      undergraduates. Posthypnotic suggestions of relaxation and analgesia did not
      influence pain ratings or tolerance, but relaxation ratings increased after RIA.
      When suggestions for analgesia were made throughout pain testing, ratings of pain
      unpleasantness at the pain tolerance point decreased more in the RIA group than
      in the attention control group. However, RIA did not influence pain threshold or
      tolerance. It was concluded that RIA was more effective in reducing subjective
      reports of pain (particularly the affective component) than in altering pain
      tolerance, and that maintenance of hypnotic suggestions was more effective than
      posthypnotic suggestions of comfort and relaxation in alleviating the affective
      component of pain.

PMID- 11294116
TI  - Indexing the experience of sex change in hypnosis and imagination.
AB  - The authors suggested a change of sex to high hypnotizable participants in
      hypnosis and imagination conditions and indexed the subjects' experiences with a
      continuous, concurrent behavioral measure that involved them turning a dial to
      indicate changes in the strength of the suggested effect. In addition, the
      researchers indexed the participants' experiences through retrospective ratings
      of realness, involuntariness, and active thinking. The dial rating showed that
      the onset of the experience was more rapid for hypnotic than for imagination
      participants. Moreover, there were differences in the relationship between dial
      ratings and retrospective ratings across the conditions as well as across the
      suggestion, test, and cancellation phases of the item. The findings are discussed
      in terms of how the dial method provides a better understanding of suggested sex
      change as well as a better understanding of the private experience of hypnosis
      and imagination.

PMID- 11294117
TI  - The Stanford Hypnotic Susceptibility Scale, Form C: normative data of a Dutch
      student sample.
AB  - Norms for the Dutch language version of the Standford Hypnotic Susceptibility
      Scale, Form C (SHSS:C; Weitzenhoffer & Hilgard, 1962) are presented. These norms
      are based upon a sample of 135 students at a Dutch university. Generally, the
      psychometric properties of the Dutch version of the SHSS:C are similar to other
      language versions. However, the mean score was somewhat lower than that found in
      the original norming studies at Stanford University.

PMID- 11294118
TI  - Contemporary psychoanalysis and hypnosis.
AB  - The relationship between psychoanalysis and hypnosis is presented in three parts:
      past, present, and future. First, the parallel developments in psychoanalysis and
      hypnosis over the past 100 years are summarized. Four major theoretical
      evolutions in psychoanalysis (drive theory, ego psychology, object relations
      theory, and self psychology) are described, with their corresponding influences
      on the practice of psychoanalytically informed hypnosis. Second, four
      contemporary movements in psychoanalysis are enumerated (postmodernism,
      spontaneity, pluralism, and integrationism), with commentary on these movements'
      likely impact on the current and future practice of hypnosis. Finally, the impact
      of shrinking mental health dollars on the practice of psychoanalysis and
      psychoanalytically informed treatments is presented. Hypnosis is offered as
      uniquely positioned, with its history of multitheoretically informed brief
      interventions, grounded in research and clinical practice, to provide
      psychoanalysis with a life raft into the next 100 years of practice.

PMID- 11294119
TI  - ODE to both a Grecian urn and a Roman aqueduct: commentary on Mary Jo Peebles
      Klieger's paper entitled, "Contemporary psychoanalysis and hypnosis".

PMID- 11294120
TI  - Is the hypnotized subject complying.
AB  - To examine the role of compliance in responses to hypnotic suggestions, the
      authors administered a number of suggestions in the standard hypnotic manner and,
      also, with urging to comply. Participants' overt behavioral responses were noted,
      and they were questioned about their subjective experience of the suggestions,
      with electrodermal skin conductance responses providing a measure of the
      truthfulness of their reports. Results indicated that, although behavioral and
      verbal responses were consistent with the hypnotic suggestions under both
      instructional sets, responses in the standard hypnotic setting appeared to be
      experienced as genuine. That is, reports of subjective experiences met the
      criterion for truthfulness, whereas reports of suggested experiences administered
      with urging to comply did not meet the criterion for truthfulness.

PMID- 11294121
TI  - Anterior brain functions and hypnosis: a test of the frontal hypothesis.
AB  - Neuropsychological frontal lobe tests were used to compare individuals with high
      (n = 8) and low (n = 9) hypnotizability during both baseline and hypnosis
      conditions. Subjects were assessed on two hypnotic susceptibility scales and a
      test battery that included the Stroop test, word fluency to letter- and semantic
      designated categories, tests of simple reaction time and choice reaction time, a
      vigilance task, and a questionnaire of 40 self-descriptive statements of focused
      attention. Effects for hypnotic susceptibility and hypnosis/control conditions
      were scant across the dependent variables. High hypnotizables scored higher on
      the questionnaire at baseline, and their performance on the word-fluency task
      during hypnosis was reduced to a greater extent than lows. Findings indicate that
      although the frontal area may play an important role regarding hypnotic response,
      the mechanisms seem to be much more complex than mere general inhibition.

PMID- 11294122
TI  - A structured approach to evaluating change among sexual offenders.
AB  - Presently, there are no established scales that evaluate change in risk among
      sexual offenders. The Sex Offender Need Assessment Rating (SONAR) was developed
      to fill this gap. The SONAR includes five relatively stable factors (intimacy
      deficits, negative social influences, attitudes tolerant of sex offending, sexual
      self-regulation, general self-regulation) and four acute factors (substance
      abuse, negative mood, anger, victim access). The psychometric properties of the
      scale were examined using data previously collected by Hanson and Harris (1998,
      2000). Overall, the scale showed adequate internal consistency and moderate
      ability to differentiate between recidivists and nonrecidivists (r = .43; ROC
      area of .74). SONAR continued to distinguish between the groups after controlling
      for well-established risk indicators, such as age, and scores on the Static-99
      (Hanson & Thornton, 2000) and the Violence Risk Appraisal Guide (Quinsey, Harris,
      Rice, & Cormier, 1998).

PMID- 11294123
TI  - Empathy deficits and cognitive distortions in child molesters.
AB  - An attempt was made to examine the thesis that the apparent empathy deficits in
      child molesters are simply another aspect of their self-serving tendency to
      distort information by, in this case, failing to recognize victim harm. Thirty
      four child molesters were compared on a victim empathy measure and a measure of
      cognitive distortions, with 24 nonsex offenders and 28 nonoffending males. Child
      molesters displayed greater cognitive distortions than the other subjects and
      their greatest empathy deficits were toward their own victims. Consistent with
      the theory being examined it was found that the empathy scores of the child
      molesters toward their own victims were significantly correlated with the
      responses to the cognitive distortions scale. The results are discussed in terms
      of their implications for theory and practice.

PMID- 11294124
TI  - Predictors of recidivism in Australian juvenile sex offenders: implications for
      treatment.
AB  - Juvenile sex offenders charged with their first sexual offense were compared with
      recidivist juvenile sex offenders who had been charged with more than one sexual
      offense on a number of factors related to sexual offending. Participants were 70
      male juvenile sex offenders, aged 13-21 years who were awaiting court
      disposition. Negative family history, negative family characteristics, school and
      learning problems, social skill deficits, deviant sexual experiences, deviant
      sexual fantasies, and cognitive distortions were assessed for their direct and
      mediating roles in recidivism. Path analysis indicated that poor social skills,
      learning problems, and deviant sexual experiences were causally related to
      recidivism of sexual offending. Poor social skills were directly related to
      recidivism, whereas cognitive distortions and deviant sexual fantasies mediated
      the role of learning problems and deviant sexual experiences. There was a
      significant association between deviant sexual experience and learning problems.
      The findings support the role of cognitive distortions and deviant sexual
      fantasies in recidivist sexual offending for this sample. The causal role
      identified for poor social skills and learning problems in recidivism for sexual
      offending has implications for treatment and therefore deserves further
      attention.

PMID- 11294125
TI  - Goal attainment scaling with sexual offenders: a measure of clinical impact at
      posttreatment and at community follow-up.
AB  - The impact of cognitive-behavioral interventions was assessed for 28 low-moderate
      risk and 20 high-risk sexual offenders on conditional release to the Greater
      Toronto Area. Goal Attainment Scaling (GAS--T. Hogue, 1994) for sexual offenders
      was used to rate clinical and motivational elements of treatment taken from
      reports written at pretreatment, posttreatment, and after 3 months of community
      follow-up. Results indicated that both groups of offenders benefited from
      treatment, although low-moderate risk offenders showed consistently better
      results on all measures. Performance along nonrelapse prevention related
      dimensions increased from pretreatment to posttreatment and remained relatively
      steady in the community. Relapse prevention related treatment components showed a
      steady increase from pretreatment throughout follow-up in the community for low
      moderate risk offenders, but not for high-risk offenders. Both groups improved
      substantially in level of motivation from pretreatment to posttreatment; however,
      only those in the low-moderate risk group maintained their motivation levels once
      released to the community. These results are discussed with respect to the
      effectiveness of cognitive-behavioral treatment of sexual offenders.

PMID- 11294126
TI  - Calculating number of offenses and victims of juvenile sexual offending: the role
      of posttreatment disclosures.
AB  - This research was designed to compare data obtained from agency records at three
      treatment programs for juvenile male sex offenders with information available
      from clinicians once youth and their families had been in treatment for at least
      6 months. Results revealed that over the course of treatment, youth and their
      families disclosed information about additional victims and offenses, physical
      and sexual abuse of the offenders, and several aspects of a violent and
      sexualized family environment. Over half the boys reported additional victims or
      additional offenses or both. There were significant increases in the number of
      reports of physical abuse, witnessing of domestic violence, living in a sexual
      environment, maternal sexual victimization, maternal victimization of domestic
      violence, and fathers being perpetrators of domestic violence. These data clearly
      support the hypotheses of the study and have important implications for both
      clinical practice and future research in this area.

PMID- 11294127
TI  - An exploration of factors related to deviant sexual arousal among juvenile sex
      offenders.
AB  - To date, there has been limited literature on the measurement of sexual arousal
      in adolescent sex offenders. The data that exist have been somewhat mixed in
      terms of factors related to deviant sexual arousal in this group. The present
      study, with 71 adolescent sex offenders, investigates the relationship between
      offender and offense characteristics, including gender of victim, history of
      sexual abuse, history of physical abuse, race, and interactions between these
      factors in the prediction of physiologically measured sexual arousal to deviant
      and nondeviant stimulus categories. A number of variables significantly predicted
      sexual arousal. The most consistent predictors were gender of victim, race, the
      interaction of race and gender of victim, and to some extent the interaction of
      offender abuse history and gender of victim. Caucasian subjects tended to respond
      more than African American subjects did, and this has not been reported
      previously in the literature. The data are discussed in terms of consistency with
      other literature, suggesting that those juvenile offenders who target male
      victims and have been abused themselves may be a high risk group. Limitations of
      this study are also addressed.

PMID- 11294128
TI  - Natural polyamines and their biological consequence in mammals.
AB  - The polyamines (putrescine, cadaverine, agmatine, spermidine and spermine), wide
      spread in all organisms, have been shown to play a role in regulation of growth
      and differentiation of virtually all types of cells. Their role in many
      physiological and pathophysiological processes have been studied very intensively
      during the last two decades. Inhibitors of polyamine biosynthesis have potential
      clinical uses as antitumor and antiparasitic agents. The brief summary with
      regard to their biological consequences in mammals is discussed in this paper.

PMID- 11294129
TI  - Effect of acetyl-L-carnitine on leukemia L1210 resistant to mitoxantrone.
AB  - Supportive care in tumour chemotherapy is a subject of intensive research. The
      complications of cytostatic therapy are a cause of extensive research of their
      pharmacological interactions and side effects. The immunologic and biochemical
      changes accompanying tumours are the factor that is most responsible for the
      worsening of the physiology of the host. Regimens containing carnitine and it's
      acetyl-derivative are used in many cases, among others even for preventing
      hepatotoxicity. Our hypothesis was to verify the supporting metabolic effects of
      acetyl-L-carnitine hydrochloride (ALC) in combined therapy with mitoxantrone (MX)
      and hepatotoxic cytostatic drugs including alkylating agents. This present report
      describes the effect of ALC in combination with MX on DBA/2 male mice bearing a
      transplantable L1210 leukemia resistant to MX. The criterion for evaluation of
      effect was the length of survival time of experimental animals. The proportional
      hazards model quadratic in the drug dose (7) was used for survival time
      evaluation and optimal dose calculation. The hazard functions and the index of
      relative hazard were determined using Weibull distribution after logarithmic
      transformation of the entered data in each particular group. The dose-response
      curve was represented by a second-degree polynomial without absolute term. The
      combination therapy revealed that the optimal dose of ALC was 186 mg/kg s.c. This
      relation is shown in Fig.1. A significant effect of ALC (s.c.) in combined
      therapy with MX (6 mg/kg i.v.) given to animals bearing an experimental form of
      leukemia L1210/MX resistant to MX was proven at a level of probability p < or =
      0.001. The effect of ALC in monotherapy was not demonstrable.

PMID- 11294130
TI  - Long-term effect of fibre supplement and reduced energy intake on body weight and
      blood lipids in overweight subjects.
AB  - A weight-reducing potential has been ascribed to high dietary fibre intake. To
      investigate the practical reliability of this hypothesis, fifty-three moderately
      overweight females (BMI > 27.5 kg/m2) on reduced energy intake (1200 kcal/day)
      were treated for 24 weeks with a fibre supplement on a randomly, double-blind,
      placebo-controlled basis. The fibre was administered as an initial dose of 6 g
      and a maintenance dose of 4 g. Body weight and blood pressure were recorded
      weekly during the first 3 months and thereafter every second week. Blood samples
      were drawn at start and at end of the study. Initial body weights were 75.6 +/-
      1.6 kg in the fibre group versus 75.5 +/- 1.6 kg in the placebo group. After
      treatment, mean weight loss in the fibre group was 8.0 kg versus 5.8 kg in the
      placebo group (p < 0.05). Systolic and diastolic blood pressures were
      significantly reduced in both groups without differences between the groups.
      Serum concentrations of cholesterol, triglycerides and uric acid were
      significantly reduced in the group with reduced energy intake, whereas no
      additional effect was observed when fibre was supplemented. Serum concentrations
      of potassium and sodium did not change significantly. The results suggest that a
      dietary fibre supplement in combination with a hypocaloric diet is of value as an
      adjunct in the management of overweight.

PMID- 11294131
TI  - Costs and outcomes of use of amitriptyline, citalopram and fluoxetine in major
      depression: exploratory study.
AB  - BACKGROUND: The increasing cost of pharmaceuticals in the Czech Republic has led
      to the restriction on prescriptions of expensive new antidepressants. The aim of
      the study was to compare the costs and outcomes of using amitriptyline,
      citalopram and fluoxetine in the treatment of major depression. METHODS: Ninety
      patients (69 women) with a mean age of 44.5 years (S.D. = 14.3) suffering from
      major depression were treated with amitriptyline (N = 31), citalopram (N = 29)
      and fluoxetine (N = 30). Direct medical costs and effectiveness (indicated by the
      number of hospitalization-free days) were assessed in a prospective, open, intent
      to-treat study. RESULTS: Neither cost nor effectiveness were significantly
      different among the treatment groups. CONCLUSION: Amitriptyline treatment is not
      less expensive nor more effective than citalopram or fluoxetine therapies. There
      is no advantage in restricting patients from treatment with SSRIs, which have
      fewer adverse effects and a decreased risk of a lethal overdosage in comparison
      with tricyclic antidepressants.

PMID- 11294132
TI  - Propaedeutic, basis for constitution, and statute of the bank of human embryonic
      and fetal cells.

PMID- 11294133
TI  - [The list of publication in the journal "Meditsina Truda i Promyshlennaia
      ekologiia" in 2000].

PMID- 11294134
TI  - Neuronal nicotinic receptors: no smoke without fire!

PMID- 11294135
TI  - Demyelinating diseases: from pathogenesis to repair strategies.

PMID- 11294136
TI  - Directing AMPA receptor traffic.

PMID- 11294137
TI  - Lipid profile of nutrition students and its association with cardiovascular
      disease risk factors.
AB  - OBJECTIVE: To describe the lipid profile and to verify its relationship with
      cardiovascular disease risk factors in students at a public university in Sao
      Paulo. METHODS: After obtaining clinical, anthropomorphic, and lipid profile data
      from 118 students, variables of the lipid profile were related to other risk
      factors. RESULTS: The mean age of the students was 20.3 years (SD = 1.5). The
      risk of cardiovascular disease was characterized by a positive family history of
      ischemic heart disease in 38.9%; sedentariness in 35.6%; limiting and increased
      total and LDL-C cholesterol levels in 17.7% and 10.2%, respectively; decreased
      HDL-C levels in 11.1%; increased triglyceride levels in 11.1%; body mass index >
      25 in 8.5%, and smoking in 6.7% of the subjects. Students' diet was found to be
      inadequate regarding protein, total fat, saturated fat, sodium, and fiber
      contents. A statistically significant association between cholesterol and
      contraceptive use, between HDL-C and contraceptive use, age and percent body fat,
      and triglycerides and percent lean weight was observed. CONCLUSION: A high
      prevalence of some risk factors of cardiovascular disease as well as the
      association between these factors with altered lipid profiles was observed in the
      young population studied.

PMID- 11294138
TI  - Case 1/2001--a 54-year-old male with chronic myeloproliferative discover and
      pulmonary thrombotic arteriopathy.

PMID- 11294139
TI  - Diagnosis: acrodermatitis continua of Hallopeau.

PMID- 11294140
TI  - Bibliography. Current world literature. Clinical nephrology.

PMID- 11294141
TI  - Bibliography. Current world literature. Pathophysiology of hypertension.

PMID- 11294142
TI  - President Bush announces New Freedom Initiative, proposes Mental Health
      Commission.

PMID- 11294143
TI  - Youth violence: a report of the surgeon general.

PMID- 11294145
TI  - Culture and social distance: a case study of methodological cautions.
AB  - The authors presented, as a case study of methodological challenges in cross
      cultural research, E. S. Bogardus's (1925) Social Distance Scale, which requires
      respondents to indicate the social distance between themselves and others. The
      meaningfulness of the scale depends on the assumption that respondents believe
      that the magnitude of social distance increases as one moves through the social
      categories of family member, friend, neighbor, coworker, and citizen. The authors
      tested this assumption for English Canadian, French Canadian, Jewish, Indian,
      Algerian, and Greek participants, all 1st-generation immigrants in Montreal. The
      participants rated their willingness to associate with members of each of the
      other ethnic groups in 5 social categories. The percentage of respondents in each
      sample whose data conformed to the prediction ranged from 63.7% to 98.0%, with
      English Canadian, French Canadian, and Jewish respondents providing responses
      most consistent with the predicted pattern. The Indian and Algerian respondents'
      data were the least consistent with the predicted pattern, especially when rating
      members of their own ethnic groups.

PMID- 11294144
TI  - [Granulocytes transfusion for neutropenic patients].
AB  - A renewed interest in the transfusion of granulocytes for support of patients
      afflicted by severe and prolonged neutropenia has resulted from improved methods
      of mobilization and collection that provide cellular products superior in number
      and functions as compared with historical experiences of the 70's. In this review
      we discuss the clinical experience reported in the literature over the past three
      decades, the progress made in donor selection, the use of growth factors and
      mechanical apheresis. We comment on adverse effects, emphasize present
      indications and our own experience for the use of granulocyte transfusions.
      Hopefully, the progress made in this area will justify the consideration of
      granulocyte transfusions in the management of the severely neutropenic patient
      and provide proper documentation to avoid repeating the disappointment
      experienced in the previous two decades.

PMID- 11294146
TI  - Day persons, night persons, and time of birth: preliminary findings.
AB  - The authors conducted 2 surveys to determine the relationship between time of
      birth and being a day person or a night person. Day persons are most alert during
      daylight hours; night persons are most alert during hours of darkness. In Survey
      1, the authors asked U.S. high school students to complete the Alertness
      Questionnaire (B. Wallace, 1993) and to respond to other items related to daytime
      or nighttime activity. In Survey 2, the authors administered the same items to a
      U.S. college population. In both surveys, time of birth was significantly related
      to being a day person or a night person. The results suggest that a critical
      period for setting the biological clock for alertness may be the moment of birth.

PMID- 11294147
TI  - Cultural and gender differences in anger and aggression: a comparison between
      Japanese, Dutch, and Spanish students.

PMID- 11294148
TI  - A predictive study of stress among Australian dual-career couples.

PMID- 11294149
TI  - Signing the organ donor card: the relationship between expressed attitude, the
      actual behavior, and personality traits.

PMID- 11294150
TI  - Social support and the ability to adapt to life among Brazilian street children
      and non-street children.

PMID- 11294151
TI  - An examination of the relationship between chartered accountants' demographic
      backgrounds and professional examination performance.

PMID- 11294152
TI  - Implicit theories of reality and social differentiation from gay people.

PMID- 11294153
TI  - Correlates of team success in higher education.

PMID- 11294154
TI  - Helplessness, locus of control and psychological health.

PMID- 11294155
TI  - Value hierarchies of French Catholics committed to the fight against AIDS.

PMID- 11294156
TI  - African Americans' stereotypes of Whites: relationships with social dominance
      orientation, right-wing authoritarianism, and group identity.

PMID- 11294157
TI  - Social power bases of managers: emergence of a new factor.

PMID- 11294158
TI  - Age and gender differences in the self-concept of South African students.

PMID- 11294159
TI  - Self-consciousness and performance decrements within a sporting context.

PMID- 11294160
TI  - Effects of roles and performance feedback on the equality rule in resource
      sharing tasks.

PMID- 11294161
TI  - Readers' perceptions of four alternatives to masculine generic pronouns.

PMID- 11294162
TI  - Perceived accuracy of fortune telling and belief in the paranormal.

PMID- 11294163
TI  - Self-esteem as a predictor of attitudes toward wife abuse among Muslim women and
      men in Canada.
AB  - This study was designed (a) to assess attitudes toward wife abuse in a sample of
      Muslim women and men in Canada and (b) to assess whether those attitudes were
      influenced by self-esteem. Results suggested that, as in general North American
      samples, the Muslim women and men did not differ from each other on levels of
      self-esteem. Also consistent with general North American samples, the Muslim
      women's and men's attitudes toward wife abuse were related to their self-esteem,
      with higher self-esteem scores predicting stronger attitudes against wife abuse,
      independent of gender. However, the results also revealed that the Muslim men had
      significantly more lenient attitudes toward wife abuse compared with the Muslim
      women and with North American norms.

PMID- 11294164
TI  - Effects of affect, stereotype consistency, and valence of behavior on causal
      attributions.
AB  - The authors examined 3 hypotheses about the effects of 2 positive and 2 negative
      affects on causal attributions. On the basis of cognitive appraisal theories of
      emotion, they predicted that the grateful and angry participants would attribute
      causality for like-valenced behaviors to the target more strongly than would the
      happy and sad participants, respectively. Following an affect-induction
      procedure, 229 Anglo-American participants read a description of an African
      American target whose behavior was stereotype consistent or stereotype
      inconsistent and positive or negative in valence. As predicted, when the behavior
      was negative, the angry participants attributed it more strongly to the target
      than did the sad participants. When the behavior was positive, the grateful
      participants attributed it more strongly to the target than did the happy
      participants. The importance of distinguishing among affects and considering
      their multidimensional nature in predicting effects on social judgments is
      emphasized.

PMID- 11294165
TI  - Condom use among US students: the importance of confidence in normative and
      attitudinal perceptions.
AB  - The author performed a study among U.S. undergraduates to test an earlier
      conclusion (D. Trafimow, 1994) that confidence in the correctness of one's
      perceptions of normative pressure to use a condom influences the correspondence
      between those perceptions and the intentions actually to perform the behavior.
      Consistent with previous findings (Trafimow), the participants' perceptions of
      normative pressure strongly predicted their intentions to use condoms only under
      conditions of extreme normative confidence. Otherwise, their attitudes were
      better predictors of their intentions to use condoms. In addition, 2 other
      variables (attitudinal confidence and perceived behavioral control) were found to
      be unimportant predictors of intentions. Results of a 2nd study suggest that
      behaviors performed by sexual partners and knowing the sexual partners affected
      the participants' normative confidence.

PMID- 11294166
TI  - Private self-consciousness as a moderator of the relationship between value
      orientations and attitudes.
AB  - The author examined implications of private self-consciousness (PrivSC;
      Fenigstein, Scheier, & Buss, 1975) for the relationships between social values
      and issue attitudes. Indeed, the author expected that the value orientations of
      authoritarianism and individualism would shape attitudes toward physician
      assisted suicide. Values and attitudes were consistent in the high-PrivSC
      participants, who tended to be more aware of different beliefs held
      simultaneously than were the low-PrivSC participants. However, for the low-PrivSC
      individuals, there was no relationship between values and attitudes. The results
      of 2 studies among U.S. undergraduate students confirmed these predictions.

PMID- 11294167
TI  - The effects of gender role orientation on team schema: a multivariate analysis of
      indicators in a US Federal health care organization.
AB  - In this empirical study of 649 employees at a federally supported health care
      facility in the United States, the authors investigated the effects of individual
      gender role orientation on team schema. The results indicated (a) that
      nontraditional male and female employees perceived the greatest amount of group
      cohesion in their team schemas and (b) that both traditional and nontraditional
      male employees perceived greater problem-solving potential in their team schemas.
      Meaningful implications for team composition are discussed.

PMID- 11294168
TI  - Relationships between proenvironmental attitudes and concepts of nature.
AB  - The author investigated relationships between proenvironmental attitudes and
      concepts of nature. Proenvironmental attitudes were measured on a 5-point scale
      containing 27 items. The author developed a 5-point scale containing 20 items to
      assess concepts of nature. The author administered those 2 scales to 140 young
      adults and adolescents at 2 Japanese institutions of higher education. An
      investigation of 6 proenvironmental attitudes and 20 concepts of nature showed
      some significant relationships. Factor analysis of the 20 concepts of nature
      produced 2 factors: Positive Evaluation of Nature and Rejection of Manipulation
      of Human Life. Most relationships were significant between the scores for the 6
      proenvironmental attitudes and those for the 2 factors of concepts of nature.

PMID- 11294169
TI  - Close relationships between Asian American and European American college
      students.
AB  - The authors examined attitudes and behaviors regarding close relationships
      between European and Asian Americans, with a particular emphasis on 5 major
      subgroups of Asian Americans (Chinese, Japanese, Korean, Vietnamese, and Filipino
      Americans). Participants were 218 Asian American college students and 171
      European American college students attending a culturally diverse university. The
      European Americans did not differentiate among the various subgroups of Asian
      Americans. Their attitudes regarding close relationships were less positive
      toward Asian Americans than toward Mexican and African Americans, a finding
      contrary to the prediction of social exchange theory (H. Tajfel, 1975). In
      contrast to the European Americans' view of homogeneity among Asian Americans,
      the 5 major subgroups of Asian Americans expressed a distinctive hierarchy of
      social preference among themselves. Results are discussed in terms of their
      implications for future research on interethnic relations involving Asian
      Americans.

PMID- 11294170
TI  - Fluctuation in autonomic tone is a major determinant of sustained atrial
      arrhythmias in patients with focal ectopy originating from the pulmonary veins.
AB  - INTRODUCTION: This study was designed to analyze dynamic changes in autonomic
      tone preceding the onset of sustained atrial arrhythmias in patients with focal
      atrial fibrillation (AF) to determine why patients with frequent discharge from
      the arrhythmogenic foci develop sustained AF. METHODS AND RESULTS: Holter tapes
      from 13 patients (10 men and 3 women; mean age 53 +/- 5 years) with paroxysmal
      "lone" AF (mean 18 +/- 13 episodes per week) and a proven focal origin (pulmonary
      veins in all cases) were analyzed. A total of 38 episodes of sustained (>30 min)
      were recorded and submitted to frequency-domain heart rate variability analysis.
      Six periods were studied using repeated measures analysis of variance: the 24
      hour period, the hour preceding AF, and the 20 minutes before AF divided into
      four 5-minute periods. A significant increase in high-frequency (HF, HF-NU)
      components was observed during the 20 minutes preceding AF (P = 0.003 and 0.002,
      respectively), together with a progressive decrease in normalized low-frequency
      (LF-NU) components (P = 0.035). An increase in LF/HF ratio followed by a linear
      decrease starting 15 minutes before sustained AF also was observed, indicating
      fluctuations in autonomic tone, with a primary increase in adrenergic drive
      followed by a marked modulation toward vagal predominance immediately before AF
      onset. CONCLUSION: In patients with focal ectopy originating from the pulmonary
      veins, sustained episodes of atrial arrhythmias are mainly dependent on
      variations of autonomic tone, with a significant shift toward vagal predominance
      before AF onset.

PMID- 11294171
TI  - Home-based long-term care.
AB  - Life expectancy is increasing in many parts of the world. Not only are more
      people living to old age, but more are also being enabled to live with disabling
      conditions that once might have been fatal. People who are chronically ill, those
      with serious disabilities, people with HIV/AIDS, mentally ill individuals, the
      victims of accidents and disasters, the elderly--many of these, and others, need
      continuing care and support. As the number of people in need of long-term care
      continues to grow worldwide, consideration of the best way to meet this need is
      receiving much more focus. The aim of such care is not simply to look after the
      sick but to enable those with long-term illnesses or disabilities to live their
      lives as fully and as rewardingly as possible. Such care is not just a social
      responsibility; it is a vital element in development. Institutionalization is
      often not the most suitable form of long-term care. The home, where the patient
      lives with family members, and where friends and other members of the community
      are not far away, is frequently more appropriate. This report by an international
      WHO Study Group examines the options. It points clearly to the benefits that home
      based care offers to the patient, while stressing that the personal and health
      needs of caregivers in the home must not be compromised. Home-based long -term
      care has been practised by families for centuries, and family members will always
      remain a valuable resource for care. This report argues that it is time for
      health systems to take responsibility for providing caregivers in families and
      communities with the support they need both to help make their tasks more
      bearable and to bring a greater share of benefit to the patient.

PMID- 11294172
TI  - Effects of isomalto-oligosaccharides on bowel functions and indicators of
      nutritional status in constipated elderly men.
AB  - OBJECTIVES: To evaluate effects of isomalto-oligosaccharides (IO) on the bowel
      function and nutritional status of elderly men. METHODS: Seven older male
      subjects participated in this study that consisted of a 30-day control low fiber
      period followed by a 30-day IO-supplemented (10 g active components) experimental
      period. Bowel functions such as defecation, enema use and bloating were monitored
      daily. Fecal characteristics such as wet and dry stool weights, stool moisture,
      pH and short-chain fatty acid contents were determined on five-day fecal
      composites collected in each period. Feces were further fractionated into plant,
      bacterial and soluble fractions to determine the bases for the increase in stool
      weight. Nutritional status of subjects was assessed with anthropometric
      parameters, nutrient intake and biochemical measurements. RESULTS: Incorporation
      of IO significantly increased the defecation frequency, wet stool output and dry
      stool weight by twofold, 70% and 55%, respectively. Fecal acetate and propionate
      concentrations significantly increased by nearly two and a half fold with IO
      supplement. The increase in stool bulk was mainly attributed by increased
      bacterial mass. Mean serum sodium concentration decreased in the experimental
      period while other blood characteristics did not change significantly.
      Anthropometric parameters and nutrient intake remained constant throughout the
      study. CONCLUSIONS: Consumption of IO effectively improved bowel movement, stool
      output and microbial fermentation in the colon without any adverse effect
      observed in this study. Therefore, supplementation of IO into ordinary low fiber
      diets may be practical in relieving constipation in the elderly population.

PMID- 11294173
TI  - Monitoring pudendal nerve function during labor.
AB  - BACKGROUND: To determine methodology and feasibility of pudendal nerve monitoring
      during labor and delivery. METHODS: With Institutional Review Board approval, 13
      low-risk, singleton pregnant women were recruited. The latency and amplitude of
      the perineal branch of the pudendal nerve compound muscle action potential were
      recorded during the second stage of labor and after delivery. With the first two
      patients, a wire electrode was used to stimulate the pudendal nerve continuously
      at the ischial spine. For the remaining 11 patients, a St. Mark's electrode was
      used to stimulate transvaginally. Aurethral ring electrode on a 14 French foley
      catheter monitored the response from the urethral sphincter. All patients
      received prophylactic antibiotics. EXPERIENCE: Twelve patients delivered
      vaginally, and one by cesarean. In two patients, continuous wire stimulation
      showed a gradual decrease in amplitude. Changes were minimal over 15-minute
      intervals. Wire electrode placement was technically difficult and dislodged
      easily. With the remaining 11 patients, all had data available for
      interpretation, and of the 85 potential perineal branch of the pudendal nerve
      compound muscle action potentials, 53 were obtained. No patients developed
      cystitis. CONCLUSION: Intrapartum assessment of pudendal nerve function is
      feasible. Continuous wire stimulation is technically more difficult and does not
      provide additional information beyond that available from intermittent
      stimulation.

PMID- 11294174
TI  - Preeclampsia and fetal growth.

PMID- 11294175
TI  - Vaginal misoprostol for cervical priming before operative hysteroscopy: a
      randomized controlled trial.

PMID- 11294176
TI  - Etiology of third-trimester maternal hyperuricemia in nonpreeclamptic twin
      gestations.

PMID- 11294177
TI  - [Chronic obstructive bronchitis (COPD). Are anticholinergic drugs
      underestimated?].

PMID- 11294178
TI  - Vasculitis of the female genital tract.

PMID- 11294179
TI  - Acute myocardial infarction: a rare complication of protein C deficiency.

PMID- 11294180
TI  - Toilet seat syndrome: renal failure, perineal gangrene, and sciatic neuropathy.

PMID- 11294181
TI  - Esophageal tuberculosis: a rare but not to be forgotten entity.

PMID- 11294182
TI  - Acute myocardial infarction after aortic valve endocarditis.

PMID- 11294183
TI  - The biological assessment of the chitin fibres.
AB  - On the basis of carried laboratory tests of the aqueous extracts, such as pH
      evaluation, electric conductivity and dry residue assessment we can stated that
      the obtained results are within the limits of the standards and are comparable to
      these given for similar kinds of medical devices, e.g. for Dexon sutures: pH-
      6.10; electric conductivity--31 MicroScm-1; dry residue after evaporation--0.0014
      g/100 cm3. The mean percentage of hemolysis counted from the three samples made
      for chitin extracts was 0.86% and did not exceed the value of 1% which is
      accepted by the standards. In the assessment of the cytotoxicity which was
      carried out on the mouse fibroblasts, the proper morphological character was
      stated. Agglutination, vacuolisation, nor cells membrane lysis were not observed.
      The number of cells separated from the matrix were identical as in the control
      cultures. The increased number of the dead cells and decreased proliferation of
      the cells in the cultures containing the chitin extracts, were probably due to
      the ethylene oxide residues, which was used for sterilisation of the fibres. The
      assessment of the intracutaneous reactivity of the chitin extracts showed the
      lack of the irritation influence and the index of primary irritation was of no
      importance at all. The pathomorphological findings, which included macroscopic
      and microscopic evaluation, specially carried out after the implantation, showed
      the greater biocompatibility of the tested chitin fibres in comparing them to the
      Maxon sutures. The healing process of these fibres included the short exudative
      phase, which was more significant than in Maxon sutures reaction followed by the
      proliferation phase, which ended with the development of the connective tissue
      capsule. The connective tissue penetrated among the single chitin fibres. After
      longer observation periods (more then 30 days) the thickness of the capsule
      decreased. The number of the chitin fibres did not change over the observations
      periods, however the change of the colour of the fibres was observed. In our
      opinion it is the sign that the process of resorption has already started. The
      tissue reactions after implantation of the chitin fibres can be compared to those
      observed for monofilament suture Maxon. On the basis of all these observations,
      assessments and findings we can stated that the chitin fibres fulfil the basic
      biological requirements set up for the bio-medical devices.

PMID- 11294184
TI  - Person to person.

PMID- 11294185
TI  - 1Q[3a] What should be done to improve patient safety?

PMID- 11294186
TI  - Reporting coding misdeeds?

PMID- 11294187
TI  - Medication safety issue brief. Asking consumers for help. Part 3.
AB  - When hospitals examine the way caregivers prescribe and deliver medications, it
      is easy to overlook a key participant in the process: the patient. And yet,
      patients can be invaluable partners in the drive to maintain safety. Educating
      consumers about what to expect in the hospital and how to recognize a problem
      adds a layer to the safety effort.

PMID- 11294189
TI  - Nitric oxide and peroxynitrite in postischemic myocardium.
AB  - Alterations in the production of nitric oxide (NO.) are a critical factor in the
      injury that occurs in ischemic and reperfused myocardium; however, controversy
      remains regarding the alterations in NO. that occur and how these alterations
      cause tissue injury. As superoxide generation occurs during the early period of
      reperfusion, the cytotoxic oxidant peroxynitrite (ONOO-) could be formed;
      however, questions remain regarding ONOO- formation and its role in postischemic
      injury. Electron paramagnetic resonance spin trapping studies, using the NO. trap
      Fe(2+)-N-methyl-D-glucamine dithiocarbamate (Fe-MGD), and chemiluminescence
      studies, using the enhancer luminol, have been performed to measure the magnitude
      and time course of NO. and ONOO- formation in the normal and postischemic heart.
      Isolated rat hearts were subjected to control perfusion, or ischemia followed by
      reperfusion in the presence of Fe-MGD with electron paramagnetic resonance
      measurements performed on the effluent from these hearts. Whereas only trace
      signals were present prior to ischemia, prominent NO. adduct signals were seen
      during the first 2 min of reflow. The reperfusion associated increase in these
      NO. signals was abolished by nitric oxide synthase inhibition. In hearts perfused
      with luminol to detect ONOO- formation, a similar marked increase was seen during
      the first 2 min of reperfusion that was blocked by nitric oxide synthase
      inhibitors and by superoxide dismutase. Either NG-nitro-L-arginine methyl ester
      or superoxide dismutase treatment resulted in more than twofold higher recovery
      of contractile function than in untreated hearts. Immunohistology studies
      demonstrated that the ONOO(-)-mediated nitration product nitrotyrosine was formed
      in postischemic hearts, but not in normally perfused controls. Thus, NO.
      formation is increased during the early period of reperfusion and reacts with
      superoxide to form ONOO-, which results in protein nitration and myocardial
      injury.

PMID- 11294191
TI  - [New indications for beta blockers. Cave hypertension focus/heart failure].

PMID- 11294190
TI  - Pharmacology of caspase inhibitors in rabbit cardiomyocytes subjected to
      metabolic inhibition and recovery.
AB  - Protection of ischemic myocardium is an important unmet need in reperfusion
      therapy of acute myocardial infarction. Myocardial ischemia and reperfusion
      induce necrosis and apoptosis in cardiomyocytes. Caspase processing and
      activation are critical steps in most receptor and nonreceptor pathways of
      apoptosis. Caspase inhibitors have been shown to reduce ischemia reperfusion
      injury in cardiac muscle. Information about dose response and time of
      administration are needed to optimize the design of preclinical studies. We used
      isolated adult rabbit cardiomyocytes subjected to metabolic inhibition (MI) and
      recovery to examine the role of caspases and caspase inhibitors, the dose
      response, and the timing of administration. In vitro inhibitory concentrations
      (Ki) were determined for purified caspases. Cardiomyocytes subjected to MI were
      treated with peptidomimetic fluoromethyl ketone inhibitors of caspases before or
      during MI, or at recovery. Caspase inhibitors were most effective when added
      before MI and included throughout recovery, but were partially protective if
      added after MI. The optimal concentration of the inhibitors tested was
      approximately 10 microM. Protection was sustained when cells were allowed to
      recover for 4 or 24 h. These results suggest that caspase activation is an
      important component of myocyte injury mediated by MI and recovery. Low doses of
      caspase inhibitors were identified that reduce injury in this model system, and
      further investigations using in vivo models are warranted.

PMID- 11294192
TI  - Managed health care not the answer.

PMID- 11294193
TI  - AIDS research. Merck reemerges with a bold AIDS vaccine effort.

PMID- 11294194
TI  - Clinical research. Fred Hutchinson Center under fire.

PMID- 11294195
TI  - Astrophysics. Farthest supernova yet bolsters dark energy.

PMID- 11294196
TI  - Venice preservation. Climate change data prompt new review.

PMID- 11294197
TI  - Bush appointment. Venture capitalist to lead science panel.

PMID- 11294198
TI  - Germany. A big boost for postgenome research.

PMID- 11294200
TI  - Japan. Court backs lab's safety practices.

PMID- 11294199
TI  - Germany. Old guard battles academic reforms.

PMID- 11294201
TI  - Reproductive science. Human cloning plans spark talk of U.S. ban.

PMID- 11294203
TI  - Astronomy. Comet's course hints at mystery planet.

PMID- 11294202
TI  - Stem cell policy. Canadian panel aims for middle ground.

PMID- 11294204
TI  - Ecology. Words (and axes) fly over transgenic trees.

PMID- 11294206
TI  - Science in Britain. Science centers blossom, but how many will survive?

PMID- 11294205
TI  - Greenhouse effects. High CO2 levels may give fast-growing trees an edge.

PMID- 11294207
TI  - Lunar and planetary science conference. Rethinking water on Mars and the origin
      of life.

PMID- 11294210
TI  - Solid-state physics. Nanotube 'peapods' show electrifying promise.

PMID- 11294209
TI  - Comparative genomics. Gene expression differs in human and chimp brains.

PMID- 11294208
TI  - Longevity. Growing old together.

PMID- 11294211
TI  - Considerations in creating online archives.

PMID- 11294212
TI  - For free access, follow the   brick red buttons.

PMID- 11294213
TI  - What's in a PhyloCode name?

PMID- 11294215
TI  - Essays on science and society. James Watt and the Lunaticks of Birmingham.

PMID- 11294214
TI  - Searching for the heart of human nature.

PMID- 11294217
TI  - Optical materials. Bending light the wrong way.

PMID- 11294216
TI  - Microbiology. Bacterial population genetics and disease.

PMID- 11294218
TI  - Atmospheric science. Solving the PSC mystery.

PMID- 11294219
TI  - Ecology. Keystone species--hunting the snark?

PMID- 11294221
TI  - Superconductivity. How could we miss it?

PMID- 11294220
TI  - Molecular biology. The histone modification circus.

PMID- 11294222
TI  - How do people know?
AB  - To fully understand processes of knowing and knowledge acquisition, it is
      necessary to examine people's understanding of their own knowing. Individual and
      developmental differences in what it means to know something, and hence in the
      criteria for justifying knowledge claims, have potentially wide-ranging
      implications. In providing support for a claim, young children have difficulty
      differentiating explanation of why a claim makes sense and evidence that the
      claim is true. Epistemic understanding progresses developmentally, but
      substantial variation remains among adults, with few adults achieving
      understanding of the complementary strengths and weaknesses of evidence and
      explanation in argument. Epistemic understanding shapes intellectual values and
      hence the disposition (as opposed to competence) to exercise intellectual skills.
      Only its most advanced levels support a disposition to engage in the intellectual
      effort that reasoned argument entails. The sample case of juror reasoning
      illustrates how epistemic understanding underlies and shapes intellectual
      performance.

PMID- 11294223
TI  - Emotion knowledge as a predictor of social behavior and academic competence in
      children at risk.
AB  - Following leads from differential emotions theory and empirical research, we
      evaluated an index of emotion knowledge as a long-term predictor of positive and
      negative social behavior and academic competence in a sample of children from
      economically disadvantaged families (N = 72). The index of emotion knowledge
      represents the child's ability to recognize and label emotion expressions. We
      administered control and predictor measures when the children were 5 years old
      and obtained criterion data at age 9. After controlling for verbal ability and
      temperament, our index of emotion knowledge predicted aggregate indices of
      positive and negative social behavior and academic competence. Path analysis
      showed that emotion knowledge mediated the effect of verbal ability on academic
      competence. We argue that the ability to detect and label emotion cues
      facilitates positive social interactions and that a deficit in this ability
      contributes to behavioral and learning problems. Our findings have implications
      for primary prevention.

PMID- 11294224
TI  - On the bistability of sine wave analogues of speech.
AB  - Our studies revealed two stable modes of perceptual organization, one based on
      attributes of auditory sensory elements and another based on attributes of
      patterned sensory variation composed by the aggregation of sensory elements. In a
      dual-task method, listeners attended concurrently to both aspects, component and
      pattern, of a sine wave analogue of a word. Organization of elements was indexed
      by several single-mode tests of auditory form perception to verify the perceptual
      segregation of either an individual formant of a synthetic word or a tonal
      component of a sinusoidal word analogue. Organization of patterned variation was
      indexed by a test of lexical identification. The results show the independence of
      the perception of auditory and phonetic form, which appear to be differently
      organized concurrent effects of the same acoustic cause.

PMID- 11294225
TI  - Brain-mind states: reciprocal variation in thoughts and hallucinations.
AB  - The exclusion of thinking from recent studies of sleep mentation has hindered a
      full appreciation of how cognitive activity differs across the states of waking
      and sleep. To overcome this limitation, this study investigated thoughts and
      hallucinations using experience sampling, home-based sleep-wake monitoring, and
      formal analyses of the psychological data. The prevalence of thoughts decreased
      gradually from waking through sleep onset and non-REM sleep, to reach its nadir
      in REM sleep, whereas hallucinations increased sharply across these states.
      Furthermore, multiple occurrences of hallucinations but not of thoughts increased
      significantly from sleep onset through non-REM sleep, to a peak in REM sleep.
      This reciprocity in thoughts and hallucinations might reflect a progressive shift
      from high to low aminergic-to-cholinergic neuromodulatory ratios across wake
      sleep states, accompanied by an array of changes in the regional activation
      patterns of the brain.

PMID- 11294226
TI  - Viewpoint dependence in visual and haptic object recognition.
AB  - On the whole, people recognize objects best when they see the objects from a
      familiar view and worse when they see the objects from views that were previously
      occluded from sight. Unexpectedly, we found haptic object recognition to be
      viewpoint-specific as well, even though hand movements were unrestricted. This
      viewpoint dependence was due to the hands preferring the back "view" of the
      objects. Furthermore, when the sensory modalities (visual vs. haptic) differed
      between learning an object and recognizing it, recognition performance was best
      when the objects were rotated back-to-front between learning and recognition. Our
      data indicate that the visual system recognizes the front view of objects best,
      whereas the hand recognizes objects best from the back.

PMID- 11294227
TI  - A neural basis for expert object recognition.
AB  - Although most adults are considered to be experts in the identification of faces,
      fewer people specialize in the recognition of other objects, such as birds and
      dogs. In this research, the neurophysiological processes associated with expert
      bird and dog recognition were investigated using event-related potentials. An
      enhanced early negative component (N170, 164 ms) was found when bird and dog
      experts categorized objects in their domain of expertise relative to when they
      categorized objects outside their domain of expertise. This finding indicates
      that objects from well-learned categories are neurologically differentiated from
      objects from lesser-known categories at a relatively early stage of visual
      processing.

PMID- 11294228
TI  - Visual span in expert chess players: evidence from eye movements.
AB  - The reported research extends classic findings that after briefly viewing
      structured, but not random, chess positions, chess masters reproduce these
      positions much more accurately than less-skilled players. Using a combination of
      the gaze-contingent window paradigm and the change blindness flicker paradigm, we
      documented dramatically larger visual spans for experts while processing
      structured, but not random, chess positions. In addition, in a check-detection
      task, a minimized 3 x 3 chessboard containing a King and potentially checking
      pieces was displayed. In this task, experts made fewer fixations per trial than
      less-skilled players, and had a greater proportion of fixations between
      individual pieces, rather than on pieces. Our results provide strong evidence for
      a perceptual encoding advantage for experts attributable to chess experience,
      rather than to a general perceptual or memory superiority.

PMID- 11294229
TI  - Attentional demands following perceptual skill training.
AB  - Practicing simple visual tasks induces substantial improvement. We investigated
      whether increased efficiency is accompanied by automaticity and immunity to
      across-task interference. We found that although practice speeds orientation
      feature detection, it does not abolish susceptibility to interference from
      introduction of concurrent central-letter identification, which takes priority.
      Yet following training with each task observers successfully managed to perform
      the tasks concurrently. The effectiveness of separate training implies that the
      role of improved intertask coordination in achieving concurrent performance was
      minor. Indeed, even when initial training was concurrent, improvement on the two
      tasks was sequential, and the higher-priority (central) task was learned first.
      However, automatic processing was not accomplished either, because increasing the
      difficulty of the higher-priority task interfered with performance of both tasks.
      What appears to be orchestrated posttraining performance is actually mainly an
      emergent property of speeded initial processes rather than either eliminated
      bottlenecks or improved central executive management.

PMID- 11294230
TI  - Lesbians and their sisters as a control group: demographic and mental health
      factors.
AB  - Lesbians and their heterosexual sisters were compared on demographic variables
      and mental health subscales, so that the feasibility of using heterosexual
      sisters as a control group for lesbians could be investigated Lesbians were
      significantly more educated, more likely to live in urban areas, and more
      geographically mobile than their heterosexual sisters. Heterosexual sisters were
      more likely than lesbians to be married and homemakers, to have children, and to
      identify with a formal religion. There was no difference in mental health, but
      lesbians had higher self-esteem. When all respondents were included, bisexual
      women had significantly poorer mental health than did lesbians and heterosexual
      women. This is the first study to use sisters as a control group in lesbian
      research.

PMID- 11294231
TI  - Six-month-old infants' preference for lexical words.
AB  - Previous work has shown that newborn infants categorically discriminate the
      fundamental syntactic category distinction between lexical and grammatical words.
      In this article, we show that by the age of 6 months, infants prefer to listen to
      lexical over grammatical words. In Experiment 1, infants were habituated to a
      list of either lexical or grammatical words, and then tested on new lists of
      words from the same and the contrasting categories. The infants showed recovery
      to lexical words after habituation to grammatical words but not vice versa. This
      asymmetry indicates a possible preference for lexical words. In Experiments 2 and
      3, preference was assessed directly by presenting infants with alternating trials
      of lexical and grammatical words, in the central-fixation preference procedure.
      The infants looked significantly longer during lexical-word than grammatical-word
      trials. These results show that by 6 months, infants attend preferentially to
      lexical words. The implications of this emerging attentional preference for
      subsequent language acquisition are discussed.

PMID- 11294232
TI  - The spatial distribution of inhibition of return.
AB  - Inhibition of return (IOR) refers to the finding that response times (RTs) are
      typically slower for targets at previously attended (cued) locations than for
      targets at novel (uncued) locations. Although previous research has indicated
      that IOR may spread beyond a cued location, the present study is the first to
      examine the spatial distribution of IOR with high spatial resolution over a large
      portion of the central visual field. This was done by using a typical IOR
      procedure (cue, delay, target) with 4 cue locations and 441 target locations
      (each separated by 1 degree of visual angle). The results indicate that IOR
      spreads beyond the cued location to affect the cued hemifield. However, the cues
      also produced a gradient of RTs throughout the visual field, with inhibition in
      the cued hemifield gradually giving way to facilitation in the hemifield opposite
      the cue.

PMID- 11294233
TI  - Memory processes and experimental continuity.
AB  - What are the memory processes that produce coherent representations of temporally
      discontinuous experiences? In this article, we describe the memory process of
      resonance, a process that provides renewed access to long-term memory information
      that is relevant to cues in working memory. Our experiments demonstrate c
      parallel waxing and waning of information as a function of relevance to a current
      episode, a pattern of accessibility of information that contributes to the
      achievement of continuity across experiences.

PMID- 11294234
TI  - Incidental learning of real-world regularities.
AB  - The large literature on incidental learning relies almost exclusively on
      laboratory experiments. Whenever researchers have attempted to demonstrate
      incidental learning of real-world regularities, they have typically failed to
      show learning. For example, it is well established that people do not learn
      regularities in everyday objects, such as the left-right orientation of faces on
      coins, despite a very large exposure to them. In this report, we examine this
      apparent contradiction. We argue that most studies exploring real-life incidental
      learning use tests that are not as sensitive to low-confidence information as
      those traditionally used in laboratory tasks. Using more sensitive measures, we
      show that it is possible to learn regularities from British and Japanese cultural
      life as a direct result of exposure to these regularities. Further, confidence
      measures suggest that although the information may be acquired incidentally, it
      can be expressed with and without concomitant awareness of that knowledge.

PMID- 11294235
TI  - How not to be seen: the contribution of similarity and selective ignoring to
      sustained inattentional blindness.
AB  - When people attend to objects or events in a visual display, they often fail to
      notice an additional, unexpected, but fully visible object or event in the same
      display. This phenomenon is now known as inattentional blindness. We present a
      new approach to the study of sustained inattentional blindness for dynamic events
      in order to explore the roles of similarity, distinctiveness, and attentional set
      in the detection of unexpected objects. In Experiment 1, we found that the
      similarity of an unexpected object to other objects in the display influences
      attentional capture: The more similar an unexpected object is to the attended
      items, and the greater its differencefrom the ignored items, the more likely it
      is that people will notice it. Experiment 2 explored whether this effect of
      similarity is driven by selective ignoring of irrelevant items or by selective
      focusing on attended items. The results of Experiment 3 suggest that the
      distinctiveness of the unexpected object alone cannot entirely account for the
      similarity effects found in the first two experiments; when attending to black
      items or white items in a dynamic display, nearly 30% of observers failed to
      notice a bright red cross move across the display, even though it had a unique
      color, luminance, shape, and motion trajectory and was visible for 5s. Together,
      the results suggest that inattentional blindness for ongoing dynamic events
      depends both on the similarity of the unexpected object to the other objects in
      the display and on the observer's attentional set.

PMID- 11294236
TI  - Representation of visuotactile space in the split brain.
AB  - Recent neurophysiological research in the monkey has revealed bimodal neuronal
      cells with both tactile receptive fields on the hand and visual receptive fields
      that follow the hands as they move, suggesting the existence of a bimodal map of
      visuotactile space. Using a cross-modal congruency task, we examined the
      representation of visuotactile space in normal people and in a split-brain
      patient (J. W.) as the right arm assumed different postures. The results showed
      that the congruency effects from distracting lights followed the hand around in
      space in normal people, but failed to do so in the split-brain patient when the
      hand crossed the midline. This suggests that cross-cortical connections are
      required to remap visual space to the current hand position when the hand crosses
      the midline.

PMID- 11294237
TI  - Changing faces: a detection advantage in the flicker paradigm.
AB  - Observers seem surprisingly poor at detecting changes in images following a large
      transient or flicker. In this study, we compared this change blindness phenomenon
      between human faces and other common objects (e.g., clothes). We found that
      changes were detected far more rapidly and accurately in faces than in other
      objects. This advantage for faces, however, was found only for upright faces in
      multiple-object arrays, and was completely eliminated when displays showed one
      photograph only or when the pictures were inverted. These results suggest a
      special role for faces in competition for visual attention, and provide support
      for previous claims that human faces are processed differently than stimuli that
      may be of less biological significance.

PMID- 11294238
TI  - Molecular physiology of odor detection: current views.
AB  - This review outlines current views of the principles and mechanisms underlying
      olfactory signaling, and presents some thoughts on open questions and future
      perspectives in this field. We briefly introduce the structure and function of
      the olfactory system and its sensory neurons, which respond to appropriate
      odorants with distinct patterns of electrical activity and contribute to the
      phenomenon of odor coding based on their characteristic receptor repertoire and
      their specific interconnections with target neurons in the brain. The molecular
      mechanisms mediating the process of chemo-electrical signal transduction in
      sensory cells and their functional implications are discussed. As a prerequisite
      for the high sensitivity and fast kinetics of the transduction process, we
      propose that the functional elements of the transduction cascades are spatially
      arranged in multimeric complexes, organized by scaffolding proteins, which anchor
      the signaling networks to the membrane of olfactory sensory cilia.

PMID- 11294239
TI  - Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+
      currents in mouse pancreatic B-cells towards negative potentials.
AB  - The effects of the chaotrophic anion perchlorate (ClO4-) on glucose-induced
      electrical activity, exocytosis and ion channel activity in mouse pancreatic B
      cells were investigated by patch-clamp recordings and capacitance measurements.
      ClO4- stimulated glucose-induced electrical activity and increased the action
      potential frequency by 70% whilst not affecting the membrane potential when
      applied in the presence of a subthreshold concentration of the sugar. ClO4- did
      not influence ATP-dependent K (KATP) channel activity and voltage-gated delayed
      K+ current. Similarly, ClO4- had no effect on Ca2+-dependent exocytosis. The
      stimulation of electrical activity and insulin secretion was instead attributable
      to an enhancement of the whole-cell Ca2+ current. This effect was particularly
      pronounced at voltages around the threshold for action potential initiation and a
      doubling of the current amplitude was observed at -30 mV. This was due to a 7-mV
      shift in the gating of the Ca2+ current towards negative voltages. The action of
      ClO4- was more pronounced when added in the presence of 0.1 mM BAY K8644, whereas
      no stimulation was observed when applied at a maximal concentration of the
      agonist (1 mM). Single-channel recordings revealed that the effect of ClO4- on
      whole-cell currents was principally due to a 60% increase in the mean duration of
      the long openings and the number of active channels. We propose that ClO4-
      stimulates insulin secretion and electrical activity by exerting a BAY K8644-like
      action on Ca2+ channel gating.

PMID- 11294240
TI  - Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through
      activation of Rho-kinase.
AB  - Arachidonic acid activates isolated Rho-kinase and contracts permeabilized smooth
      muscle fibres. Various assays were carried out to examine the mechanism of this
      activation. Native Rho-kinase was activated 5-6 times by arachidonic acid but an
      N-terminal, constitutively-active fragment of Rho-kinase, expressed as a
      glutathione-S-transferase (GST) fusion protein and including the catalytic
      subunit (GST-Rho-kinase-CAT), was not. GST-Rho-kinase-CAT was inhibited by a C
      terminal fragment of Rho-kinase and arachidonic acid removed this inhibition.
      These results suggest that the C-terminal part of Rho-kinase, containing the RhoA
      binding site and the pleckstrin homology domain, acts as an autoinhibitor. It is
      suggested further that activation by arachidonic acid is due to its binding to
      the autoinhibitory region and subsequent release from the catalytic site.
      Arachidonic acid, at concentrations greater than 30 microM, increases force in
      alpha-toxin-permeabilized femoral artery but not in Triton X-100-skinned fibres.
      The content of Rho-kinase in the latter was lower than in alpha-toxin-treated or
      intact fibres. The arachidonic acid-induced contraction was not observed at a pCa
      above 8.0 and was inhibited by Y-27632 and wortmannin, inhibitors of Rho-kinase
      and myosin light-chain kinase (MLCK), respectively. The activation of Rho-kinase
      and subsequent phosphorylation of the myosin phosphatase target subunit inhibits
      myosin phosphatase and increases myosin phosphorylation.

PMID- 11294241
TI  - G protein modulation of voltage-sensitive muscarinic receptor signalling in mouse
      pancreatic acinar cells.
AB  - Submaximal stimulation of mouse pancreatic acinar cells by acetylcholine (ACh)
      generates periodic Ca2+ responses sensitive to the membrane potential. Monitoring
      the muscarinic Ca2+ responses using patch-clamp whole-cell current recordings, we
      examined the mechanism of guanine nucleotide-binding protein (G protein)-receptor
      interaction in terms of the membrane potential. The lowest ACh concentration able
      to elicit consistent repetitive spikes was 50 nM, in the presence of which
      hyperpolarization increased and depolarization decreased the spike frequency. The
      saturating concentration was 10 microM, this induced a sustained response
      insensitive to voltage. Internal guanosine 5'-tri- and diphosphates (GTP, GDP)
      depressed and potentiated the voltage sensitivity, respectively, but not for the
      response to a saturating ACh concentration (10 microM). Internal guanosine 5'-O
      (3-thiotriphosphate) (GTPgammaS) abolished the voltage sensitivity. The results
      indicate that the ACh-induced Ca2+ response is sensitive to the membrane
      potential and that a close linkage exists between voltage sensitivity and the G
      protein association/dissociation cycle in the muscarinic receptor.

PMID- 11294242
TI  - Comparative study of the molecular and functional expression of L-type Ca2+
      channels and large-conductance, Ca2+-activated K+ channels in rabbit aorta and
      vas deferens smooth muscle.
AB  - The relationship between the density of ionic currents through major two
      channels, voltage-dependent L-type Ca2+ channels (L-type VDCC) and large
      conductance, Ca2+-activated K+ channels (BKC), and the mRNA expression levels of
      alpha1C subunit of L-type VDCC (alpha1C) and alpha/beta subunits of BKC
      (alphaBK/betaBK) were compared in smooth muscle cells (SMC) of rabbit aorta and
      vas deferens using whole cell-voltage clamp and reverse transcription-polymerase
      chain reaction (RT-PCR) analyses. The density of the currents through VDCC (ICa)
      and BKC (IK,Ca) at +10 mV in aortic SMC was approximately one-seventh and one
      sixth respectively of that in vas deferens. Whilst application of the Ca2+
      channel agonist Bay K 8644 increased ICa by 75-90% in these SMC, the increase in
      IK,Ca was far greater in aorta than in vas deferens. The expression of the
      alpha1C transcript in vas deferens was approximately 3.5 times higher than that
      in aorta. In contrast, expression of alphaBK/betaBK was almost identical in both
      tissues, indicating the dissociation of IK,Ca density from the expression levels
      of BKC transcripts in aorta. The results were supported by Western blot and
      immunocytochemical analyses using subunit-specific antibodies. The lower Ca2+
      influx through VDCC in aorta activates only a very limited fraction of BKC
      compared with that in vas deferens. The greater expression of BKC than of VDCC in
      aortic SMC contributes to a strong negative feed-back mechanism that minimizes
      membrane depolarization and acts as a safety margin to maintain low membrane
      excitability.

PMID- 11294243
TI  - Regulation of cardiac calcium current by NO and cGMP-modulating agents.
AB  - Several effects of nitric oxide (NO) on the control of L-type calcium current
      (ICa) and of calcium handling in cardiomyocytes have been described.
      Cardiomyocytes have been shown to express in different conditions all types of
      nitric oxide synthases (NOS), but the role of NO in the regulation of calcium
      current remains controversial. Previously, we have shown in guinea pig
      ventricular cells a stimulatory effect of NOS inhibitors on ICa. Here we
      investigate the intracellular mechanisms involved in the putative inhibitory role
      of NO on basal ICa in ventricular cells. The stimulatory effect of the NOS
      inhibitor NG-monomethyl-L-arginine (L-NMMA) (1 mM) was present also in calcium
      transient measurements, but only after a preincubation with L-arginine (L-arg,
      0.1 mM). The nitric oxide scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1
      oxyl-3-oxide (PTIO, 0.5 mM) increased peak ICa in a similar manner to NOS
      inhibitors in whole-cell voltage-clamp experiments. Also ODQ (1H
      [1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one, 0.1 mM), a specific inhibitor of a
      target of NO, the soluble guanylate cyclase, was able to stimulate ICa. The block
      of type II phosphodiesterase (cGMP-activated) by EHNA (erythro-9-[2-hydroxy-3
      nonylladenine, 30 microM) exerted a similar effect on ICa as PTIO and ODQ.
      Carbachol (CCh, 1 microM) was able to revert the stimulatory effect on ICa
      observed with PTIO, ODQ, and EHNA. We propose that the increase of basal ICa in
      guinea pig cardiomyocytes previously observed with L-NMMA depends on the removal
      of a tonic NO inhibition. This increase of ICa is mimicked by blocking at
      different steps the cGMP-cascade activated by NO, suggesting a NO-guanylate
      cyclase mechanism in the basal control of ventricular calcium current.

PMID- 11294244
TI  - Large-conductance calcium-activated potassium channels in neonatal rat
      intracardiac ganglion neurons.
AB  - The properties of single Ca2+-activated K+ (BK) channels in neonatal rat
      intracardiac neurons were investigated using the patch-clamp recording technique.
      In symmetrical 140 mM K+, the single-channel slope conductance was linear in the
      voltage range -60/+60 mV, and was 207+/-19 pS. Na+ ions were not measurably
      permeant through the open channel. Channel activity increased with the
      cytoplasmic free Ca2+ concentration ([Ca2+]i) with a Hill plot giving a half
      saturating [Ca2+] (K0.5) of 1.35 microM and slope of approximately equals 3. The
      BK channel was inhibited reversibly by external tetraethylammonium (TEA) ions,
      charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and
      apamin. Ionomycin (1-10 microM) increased BK channel activity in the cell
      attached recording configuration. The resting activity was consistent with a
      [Ca2+]i <100 nM and the increased channel activity evoked by ionomycin was
      consistent with a rise in [Ca2+]i to > or =0.3 microM. TEA (0.2-1 mM) increased
      the action potential duration approximately equals 1.5-fold and reduced the
      amplitude and duration of the afterhyperpolarization (AHP) by 26%. Charybdotoxin
      (100 nM) did not significantly alter the action potential duration or AHP
      amplitude but reduced the AHP duration by approximately equals 40%. Taken
      together, these data indicate that BK channel activation contributes to the
      action potential and AHP duration in rat intracardiac neurons.

PMID- 11294245
TI  - Cysteine string protein expression in mammary epithelial cells.
AB  - Cysteine string protein (Csp) is a secretory vesicle protein previously
      demonstrated to be required for Ca2+-regulated exocytosis in neurons and
      endocrine cells. It has been suggested to function by regulating voltage-gated
      Ca2+ channels or, alternatively, to have a more direct effect on the regulated
      exocytotic machinery. Here we demonstrate the expression of Csp in mammary
      epithelial cells and in the KIM-2 mammary cell line. In KIM-2 cells, Csp was
      found to be associated with a population of small vesicles and showed partial co
      distribution with the vesicle protein cellubrevin. KIM-2 cells do not express
      detectable levels of voltage-gated Ca2+ channels, ruling these out as a site of
      action. Using the release of transfected growth hormone (GH) as an assay of
      secretion, we found that GH is secreted in an exclusively constitutive manner
      from KIM-2 cells. Overexpression of Csp1 inhibits regulated exocytosis in other
      cell types but has no effect on constitutive GH release by KIM-2 cells. These
      results suggest that Csp does not have a major function in constitutive
      exocytosis.

PMID- 11294246
TI  - Relationship between pulse interval and respiratory sinus arrhythmia: a time- and
      frequency-domain analysis of the effects of atropine.
AB  - Respiratory sinus arrhythmia (RSA) estimation is commonly used as a non-invasive
      index of cardiac vagal tone. To test this relationship, vagal tone was augmented
      or blocked using atropine. The study was carried out using 14 healthy volunteers,
      following beta-adrenoceptor blockade (10 mg bisoprolol per os) and during
      controlled respiration (0.25 Hz) in order to limit the confounding effects of
      cardiac sympathetic tone and respiration pattern changes. Atropine was slowly
      infused intravenously over a 30-min period up to a vagolytic cumulative dose of
      0.04 mg/kg. The instant vagal tone was compared to the instant RSA value obtained
      from a time-/frequency-domain analysis of pulse interval (PI). RSA and PI varied
      in the same direction with an initial increase corresponding to the early
      vagomimetic effect of atropine followed by a decrease during the vagolytic phase.
      The comparative percentage fluctuations of RSA and PI over this large vagal tone
      range indicate that RSA is more sensitive (about twofold) than PI in reflecting
      fluctuations around the set point. This dissociated behaviour of PI and heart
      rate variability could be important to our understanding of the circulatory
      changes that result from fluctuations in vagal inputs to the sinus node.

PMID- 11294247
TI  - Permeability of the proximal and distal rat colon crypt and surface epithelium to
      hydrophilic molecules.
AB  - Our knowledge of the epithelial permeability of different sections of the colon
      as well as of the surface and crypt epithelium is patchy and contradictory.
      Therefore, movement of radiolabelled urea, mannitol and Cr-EDTA between the lumen
      and the plasma of rats was studied, and expressed as clearance. In experiments
      studying movement from the lumen to the plasma, only the clearance of urea was
      significant. In experiments on the movement from plasma to the lumen, all three
      permeability probes exhibited significant clearance in the proximal colon, while
      in the distal colon the clearance of Cr-EDTA was not significant and the other
      clearance values were lower than in the proximal colon. Thus, the two methods are
      proposed to mainly reflect the permeability of two different parts of the
      epithelium, i.e. the surface and the crypt epithelium. Furthermore, it is
      proposed that the rat surface epithelium only allows passage of hydrophilic
      substances smaller than monosaccharides [radius below 0.35 nm (3.5 A] while the
      crypt epithelium, particularly in the proximal colon, is a heteroporous membrane
      of higher permeability containing pores corresponding to radii of >3.5-4.0 nm (35
      40 A) and 0.4-0.5 nm (4-5 A). Moreover, the results indicate that in vivo luminal
      fluid solution has no access to the crypt epithelium, a conclusion strengthened
      by the observation that Evans-blue-labelled albumin and FITC-dextran 4000 do not
      seem to reach the crypt lumina.

PMID- 11294248
TI  - Spatial heterogeneity of energy turnover in the heart.
AB  - Local myocardial blood flow varies substantially in spite of a rather homogeneous
      morphology. To further elucidate this paradox, the spatial heterogeneity of
      tricarboxylic acid cycle turnover (J(TCA), micromol min(-1) g(-1)) and coronary
      flow was assessed at a high spatial resolution (6x6x6 mm3) in the open chest dog.
      Local flow differed more than 2.5-fold between individual samples in each heart
      (n=7). Out of 1,500 myocardial samples, 1/10 received less than 60% and another
      1/10 more than 138% of the normalized mean. In low- and high-flow samples,
      pyruvate uptake and metabolism were analyzed by 13C NMR spectroscopy. Following
      [3-13C]pyruvate infusion (2 mM, 12 min), glutamate [4-13C]/[3-13C] was
      significantly greater in low-flow (2.21+/-0.75, 40 samples) than in high-flow
      (1.64+/-0.49, 39 samples) areas. This suggests that there are major differences
      in J(TCA). Glutamate, citrate and lactate content positively correlated with
      flow. Anaplerotic pathways contributed a fraction similar to J(TCA) in low- and
      high-flow areas, as demonstrated by isotopomer analysis after 60 min of [3
      13C]pyruvate application. Mathematical model analysis of NMR data and relevant
      pool sizes revealed that J(TCA) and thus myocardial oxygen consumption (MVO2) in
      high-flow areas exceed values in low-flow areas at least threefold. Thus low and
      high metabolic states normally coexist within the well perfused heart, suggesting
      that there is considerable spatial heterogeneity of cardiac energy generation and
      work.

PMID- 11294249
TI  - Effect of nicotinic acid adenine dinucleotide phosphate on ryanodine calcium
      release channel in heart.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP), a molecule derived from
      nicotinamide adenine dinucleotide phosphate (NADP+), is a recently identified
      nucleotide that activates Ca2+ release from intracellular stores in invertebrate
      eggs and in mammalian cells. NAADP could function as an intracellular messenger
      for mobilizing internal Ca2+ stores, however the targets and nature of NAADP
      induced Ca2+ release are unknown. We report here that NAADP (3-10 microM) induces
      Ca2+ release from rat heart microsomes and that NAADP (1-10 microM) activates
      single ryanodine receptor/calcium release channels (RyR2) from dog heart
      incorporated into bilayer lipid membranes. The results indicate that NAADP may
      play a role in cardiac excitation-contraction coupling by acting on RyR2
      channels.

PMID- 11294250
TI  - Cytoplasmic Ca2+ at low submicromolar concentration stimulates mitochondrial
      metabolism in rat luteal cells.
AB  - The cytoplasmic Ca2+ signal is transferred to the mitochondrial matrix and
      activates mitochondrial dehydrogenases. The requirement for supramicromolar
      cytoplasmic [Ca2+] ([Ca2+]i) in perimitochondrial microdomains in this response
      has been suggested. We studied the correlation between [Ca2+]i, mitochondrial
      [Ca2+] ([Ca2+]m) and mitochondrial formation of reduced nicotinamide adenine
      dinucleotide (phosphate) [NAD(P)H] in the presence of submicromolar [Ca2+]i in
      cultured rat "large" luteal cells. [Ca2+]i was monitored fluorimetrically with
      fura-PE3, [Ca2+]m with rhod-2 and NAD(P)H with autofluorescence. In intact cells,
      prostaglandin F2alpha, which induces both intracellular Ca2+ release and Ca2+
      entry, stimulated mitochondrial NAD(P)H formation. Thapsigargin-induced Ca2+
      release and subsequent capacitative Ca2+ entry, both resulting in Ca2+ responses
      not exceeding 150-200 nM, also enhanced the reduction of pyridine nucleotides. As
      shown in inhibitor studies, the increased steady-state NAD(P)H level was due to
      activation of Ca2+-dependent dehydrogenases. [Ca2+]m, measured in permeabilized
      cells, increased moderately, but significantly, following elevation of [Ca2+]i
      from 50 to 180 nM, showed a further gradual increase at higher submicromolar
      [Ca2+]i values and rose steeply at supramicromolar [Ca2+]i. In summary, our
      results demonstrate that, in a steroid-producing cell type, net mitochondrial
      Ca2+ uptake and mitochondrial dehydrogenation can be activated even by low
      submicromolar increases of [Ca2+]i.

PMID- 11294251
TI  - A Na+-dependent D-mannose transporter in the apical membrane of chicken small
      intestine epithelial cells.
AB  - The presence of a Na+/D-mannose cotransporter in brush-border membrane vesicles
      (BBMV) isolated from chicken small intestine was examined. In the presence of an
      electrochemical gradient for Na+, but not in its absence, D-mannose was
      accumulated transiently by the BBMV. D-Mannose uptake into the BBMV was energized
      by both the membrane potential and the chemical gradient for Na+. The
      relationship between D-mannose transport and external D-mannose concentration was
      described by an equation that represented the superposition of a saturable
      component (Michaelis-Menten constant Km 12.5 microM) and another component
      unsaturatable up to 80 microM D-mannose. D-Mannose uptake was inhibited by
      various substances in the following order of potency: D-mannose>>D
      glucose>phlorizin>phloretin>D-fructose. For the uptake of alpha-methyl
      glucopyranoside the order was D-glucose=phlorizin>>phloretin=D-fructose=D
      mannose. The initial rate of D-mannose uptake increased as the extravesicular
      [Na+] increased, with a Hill coefficient of 1, suggesting that the Na+:D-mannose
      cotransport stoichiometry is 1:1. It is concluded that the intestinal apical
      membrane has a saturable, electrogenic and concentration- and Na+-dependent
      mannose transport mechanism that differs from the sodium-dependent glucose
      transporter SGLT1.

PMID- 11294252
TI  - Caffeine thresholds for contraction in electrophoretically typed, mechanically
      skinned muscle fibres from SHR and WKY rats.
AB  - Caffeine was used as a tool to investigate whether the sarcoplasmic reticulum
      (SR) properties in single. mechanically skinned fibres dissected from soleus
      muscle of spontaneously hypertensive rats (SHRs) differ from those in fibres of
      the same type from age-matched, normotensive Wistar-Kyoto (WKY) rats. The fibres
      were typed electrophoretically based on myosin heavy chain (MHC) isoform
      composition. Here we show evidence that the ratio between the caffeine thresholds
      for contraction at maximal and endogenous resting SR-Ca2+ (Rcaff-th) can be used
      as an indicator for distinguishing between slow-type SR (Rcaff-th>or =0.73) and
      fast-type SR (Rcaff-th<0.73). Based on this indicator, 47.5% of the SHR-soleus
      fibres identified as type I displayed fast-type SR characteristics and 40% of the
      SHR-soleus fibres identified as type II displayed slow-type SR characteristics.
      This result explains the shorter contraction and faster relaxation of soleus
      muscles in SHRs and also suggests that SR with fast-type characteristics can co
      exist with slow-twitch MHC isoforms and vice versa.

PMID- 11294253
TI  - Characterization of the relationship between Na+ -Ca2+ exchange rate and
      cytosolic calcium in trout cardiac myocytes.
AB  - The whole-cell patch-clamp technique combined with rapid caffeine (CAF)
      applications was used to measure Na+-Ca2+ exchange (NCX) currents (I(NCX)). The
      rate of Ca2+ extrusion and the amount of Ca2+ extruded from the cell upon a rapid
      CAF exposure were obtained from I(NCX) and its time integral, respectively. This
      gave a maximal NCX rate (V(NCX)) of 151 amol pF(-1) s(-1) or 2.3 mM s(-1) and a
      half-maximal V(NCX) (K0.5) at a total cellular [Ca2+] ([Ca2+]tot) of 15.4 amol
      pF(-1). Using the same approach for the tail current induced by repolarization to
      -80 mV gave a K0.5 of 7.0 amol pF(-1) corresponding to 108 microM total or 2-4
      microM free Ca2+. The relationship between [Ca2+]tot and V(NCX) was linear in the
      physiological range. Inhibition of the SR function with cyclopiazonic acid plus
      ryanodine reduced the slope significantly from 23.2+/-1.4 to 17.6+/-1.6 s(-1),
      while ryanodine alone had no effect. The relationship between [Ca2+]tot and
      V(NCX) was steeper at more negative membrane potentials, and with identical SR
      Ca2+ loads the maximal VNCX at -10 mV was reduced to 39.7+/-2.7% of the value at 
      90 mV. Long depolarizations caused SR Ca2+ loading through reverse-mode NCX.
      Between -30 and +10 mV reverse mode V(NCX)=Vm.0.047 amol pF(-1) s(-1) mV(-1)+2.51
      amol pF(-1) s(-1), giving a reversal potential of -54 mV. In conclusion, the
      relationship between V(NCX) and [Ca2+]tot shows that the NCX is capable of
      removing a total Ca2+ transient of 60 microM at physiological heart rates, while
      reverse-mode NCX reloads the sarcoplasmic reticulum (SR) during depolarization.
      Furthermore, small alterations in the action potential configuration are
      predicted to change significantly the relative importance of the NCX in the
      regulation of cytosolic [Ca2+] and SR Ca2+ loading.

PMID- 11294254
TI  - Effects of gender on intracellular.
AB  - The present study investigated the effects of gender on intracellular [Ca2+]
      ([Ca2+]i) in freshly isolated rat cardiac myocytes. Changes in [Ca2+]i in
      response to varied extracellular [Ca2+], different stimulus frequencies and
      addition of caffeine and isoprenaline were monitored using fura-2 in both male
      and female cardiac myocytes. Increasing extracellular [Ca2+] and stimulus
      frequency resulted in significant increases in peak [Ca2+] and the amplitude of
      the Ca2+ transient in both male and female cardiac myocytes. However, as
      extracellular [Ca2+] was raised, peak [Ca2+] and the amplitude of the Ca2+
      transient increased significantly more in male than female cardiac myocytes. In
      addition a significant difference between male and female cells at each stimulus
      frequency was apparent. The time course of decay of the Ca2+ transient was
      significantly slower in female cardiac myocytes when compared with male cardiac
      myocytes, along with significantly slowed times to peak shortening and 50%
      relaxation, and a reduced extent of shortening. There was no significant
      difference in the amplitude of caffeine-induced [Ca2+]i responses between male
      and female cells, however, [Ca2+]i increased more readily in male cells than in
      female cells when isoprenaline was added. The data demonstrate that, under a
      variety of conditions, intracellular [Ca2+] rises to higher levels in cardiac
      myocytes from male as compared to female rats.

PMID- 11294255
TI  - Within-subject electrocardiographic differences at equal heart rates: role of the
      autonomic nervous system.
AB  - Various combinations of sympathetic and vagal tone can yield the same heart rate,
      while ventricular electrophysiology differs. To demonstrate this in humans, we
      studied healthy volunteers in the sitting position with horizontal legs. First,
      heart rate was increased by lowering the legs to 60 degrees and back. Thereafter,
      heart rate was increased by handgrip. In each subject, a leg-lowering angle was
      selected at which heart rate matched best with heart rate in the third handgrip
      minute. Thirteen subjects had a heart rate match better than 1%. Heart rate
      (control: 65.2+/-9.0 bpm) increased to 72.1+/-8.7 (leg lowering) and to 72.1+/
      8.8 (handgrip) bpm. QRS azimuth, QRS duration, maximal T vector, T azimuth, T
      elevation, ST duration, QRS-T angle and QT interval differed significantly
      (P<0.05) between leg lowering and handgrip (QT interval 418+/-15 versus 435+/-21
      ms). Also, septal dispersion of repolarization, assessed as the time difference
      between the apex and the end of the T wave in the V2 and V3 leads, differed
      significantly (V2: 96.7+/-19.3 versus 110.0+/-23.3 ms, P<0.01; V3: 88.7+/-19.3
      versus 97.3+/-23.3 ms; P<0.01). Hence, leg lowering and handgrip cause different
      ventricular depolarization and repolarization. The hypertensive handgrip
      manoeuvre entails a longer QT interval and probably an increased septal
      dispersion of repolarization.

PMID- 11294256
TI  - Physiologists, physiology departments and universities: discipline and
      interdisciplinarity.

PMID- 11294257
TI  - Posterior urethral valves.

PMID- 11294258
TI  - Factors affecting outcome in the management of posterior urethral valves.
AB  - Children with posterior urethral valves (PUV) are at high risk for renal failure
      (RF). The outcome of renal function is significantly influenced by early
      diagnosis and the choice of primary therapy. We reviewed the outcome of renal
      function in 58 children with PUV. The choice of therapy in each case primary
      valve fulguration, vesicostomy, or high ureterostomy--was individually decided on
      the basis of the response to initial catheter drainage of the bladder. Patient
      age at diagnosis varied from newborn to 5.5 years, and follow-up ranged from 1.6
      to 6 years (mean 3.9 years). The most common procedure was primary endoscopic
      valve ablation, which was carried out in 56.8% of cases. The other procedures
      were vesicostomy in 32.75% and high ureterostomy in 10.45%. Most neonates (66.6%)
      had RF at presentation, but one-half of them had achieved normal serum creatinine
      values at last follow-up. The recovery of renal function was lowest (33%) in
      older children where the diagnosis was delayed. A comparison between two groups
      of neonates and infants who differed on the basis of creatinine concentrations at
      1 year of age suggested a statistically significant trend: children with normal
      or near-normal serum creatinine (0.8 mg/dl or less) by 12 months of age
      maintained good renal function at the time of final evaluation (1.0 mg/dl or
      less). Children with higher creatinine values at 1 year of age continued to have
      progressive RF. Seventy-five percent of the patients who had undergone early high
      ureterostomy after failure to respond to initial catheter drainage had regained
      normal renal function. We conclude that: serum creatinine at presentation is not
      predictive of subsequent renal function, but the values after a period of urinary
      tract decompression are prognostically more useful; delay in diagnosis results in
      a poor outcome of renal function; and for optimal recovery of renal function, the
      choice of the primary procedure varies from case to case and can be determined by
      a systematic, stepwise approach (stepladder protocol).

PMID- 11294259
TI  - Laser resection of posterior urethral valves.
AB  - Laser resection (LR) of posterior urethral valves during infancy as early as
      possible after diagnosis appears to represent a safe and reliable method. In
      contrast to other procedures, LR allows valve ablation with thin cystoscopes and
      carries little risk, even in premature and newborn infants. Its application in
      seven children in the course of 2 years principally confirmed its suitability for
      use: it could be applied in all cases without any problems and led to extensive
      resection of the valve tissue and removal of the obstruction in all patients. The
      encouraging clinical findings were confirmed by control cystoscopies and
      micturating cystourethrograms. Complications arising from the method were not
      observed.

PMID- 11294260
TI  - Posterior urethral valves: the scenario in a developing center.
AB  - We have reviewed 233 patients with posterior urethral valves treated in a single
      center in Calcutta, India, over the last 20 years: 37 were neonates, 75 were
      between 1 and 12 months, 88 were between 1 and 5 years, and 33 were more than 5
      years old when first seen. The clinical presentation and methods employed in
      diagnosis and assessment are described. Primary endoscopic valve ablation was
      performed in 140 patients (60%). One or other form of diversion was done in 100
      (43%), 93 before and 7 either during or after valve ablation. The short- and long
      term results have been studied. Eleven patients died during the initial
      hospitalization, 3 died subsequently, 15 are in end-stage renal disease, 17 are
      in poor health, and 18 have been totally lost to follow-up. The remaining 169
      have been in good health for periods between 1 and 20 years. While our results of
      primary valve ablation in low-risk patients with responsible parents are as good
      as anywhere else in the world, we are concerned at our relatively high diversion
      rate and relatively poor long-term follow up; the methods being adopted to reduce
      these problems are discussed.

PMID- 11294261
TI  - Demonstration of abnormal notochord development by three-dimensional
      reconstructive imaging in the rat model of esophageal atresia.
AB  - The notochord (Nt) is believed to have a role in the development of axial organs.
      This study was undertaken to reconstruct in three dimensions (3D) the
      relationship of the Nt to abnormal development of the foregut (Fg) in the
      adriamycin-induced rat model of esophageal atresia (EA). Pregnant Sprague-Dawley
      rats were given 1.75 mg/kg adriamycin intraperitoneally on gestational days 6 9
      inclusive; control rats received i.p. saline of equal volume, or no injection.
      Rats were killed between days 11 and 14 and their embryos harvested,
      histologically sectioned serially, and stained with hematoxylin and eosin.
      Digitized photographs were taken of serial transverse sections; these photos were
      traced and used as the basis for 3D reconstruction. From day 11 the normal Nt is
      no longer in contact with the respiratory or Fg mesenchyme. In adriamycin-treated
      embryos the Nt branches abnormally as it enters the Fg mesenchyme. Adherence of
      the Nt to the mesenchyme of the Fg exerts mechanical traction pulling the upper
      Fg dorsally. The severity of the Fg abnormalities correlates with the length of
      the ventral extension of the Nt within the Fg mesenchyme: the embryo develops
      atresia of the esophagus or trachea when the Nt is grossly abnormal. The Nt
      undergoes reactive thickening in the absence of Fg structures ventral to it.
      Thus, structural lesions of the Fg (e.g., atresias) are associated with
      abnormalities of the Nt. The relationship of the Nt to the Fg mesenchyme
      determines the severity of the abnormality induced by adriamycin: extensive
      adherence produces tracheal agenesis and EA.

PMID- 11294262
TI  - Abnormalities of the tracheal cartilage in the rat fetus with tracheo-oesophageal
      fistula or tracheal agenesis.
AB  - Many infants with oesophageal atresia and tracheo-oesophageal fistula (OA/TOF)
      have associated tracheomalacia (TM), which is one of the reasons for respiratory
      complications after surgical correction of the atresia. OA/TOF was induced in the
      offspring of pregnant rats by intraperitoneal injection of adriamycin. Fetuses
      were harvested by caesarean section. The trachea, oesophagus, lungs, and stomach
      were removed en bloc and stained for cartilage using Alcian blue. The tracheas
      were examined, photographed, and relevant parameters pertaining to the tracheal
      cartilage were measured. Exposure to adriamycin resulted in a range of anatomical
      defects including OA/TOF (47%) and tracheal agenesis (TA) (41%). Adriamycin
      treated fetuses were smaller (P < 0.01), yet had longer tracheas (P < 0.001) than
      control fetuses. The OA/TOF fetuses had more tracheal cartilage rings than
      controls (P < 0.01), whereas TA fetuses had fewer (P < 0.001). Both OA/TOF and TA
      fetuses had more malformed tracheal cartilage rings than controls (P < 0.001 and
      P < 0.05, respectively). Cartilage in the proximal part of the trachea was most
      frequently and severely affected (P < 0.05). These observations clarify the
      structural abnormalities of tracheal cartilage that occur in rat fetuses with
      OA/TOF or TA induced by adriamycin, and may explain the functional disturbances
      of TM seen in OA/TOF.

PMID- 11294263
TI  - Pneumonostomy in the surgical management of bilateral hydatid cysts of the lung.
AB  - During the period 1994-1998, three patients with bilateral hydatid cysts of the
      lung (HCL) underwent operative removal of the cysts. In three of the six lungs
      operated upon the conventional technique was used: after removal of the cyst and
      suture closure of bronchial leaks, the chest was closed with an intercostal
      drainage tube. Two of these patients developed bronchopleural fistulae requiring
      rethoracotomy and prolonged hospital stays. The other three lungs were operated
      upon using the pneumonostomy technique: after excision of the cyst a separate
      catheter is fixed within the residual lung cavity and brought out through the
      adjacent chest wall, effectively marsupialising the residual cavity to the
      atmosphere. All these patients had an uneventful postoperative recovery. We
      conclude that the pneumonostomy technique is a very useful method of treating HCL
      surgically, especially when the cysts are bilateral and complicated.

PMID- 11294264
TI  - The influence of delay in closure of the abdominal wall on outcome in
      gastroschisis.
AB  - To evaluate the effect of a delay in closure of the abdominal wall (AWC) on
      outcome in the management of gastroschisis, a retrospective analysis of 91 babies
      admitted over a 7-year period (1992-1998) to a single neonatal surgical unit with
      a diagnosis of gastroschisis was carried out. Antenatal diagnosis was made in 89
      (98%) cases. Surgical intervention occurred in 90 babies at a median of 4 h
      (standard error 0.345, range 0.5-17) post-delivery. In 72 (80%) cases primary
      closure of the abdominal defect was achieved, with a silo fashioned in the
      remaining 18 (20%). One infant died prior to AWC. The median time to full oral
      feeding was 22 days (2.96, 5-160), and to discharge 28 days (4.03, 11-183). There
      was no correlation between time to AWC and any measured outcome parameter. There
      was no significant difference in mortality in those patients having closure
      before 6 h. Thus, no correlation between time to AWC and outcome was
      demonstrated. This would suggest that the time taken to optimally resuscitate a
      newborn infant prior to surgical closure does not have an adverse influence upon
      outcome and is to be recommended.

PMID- 11294265
TI  - Extracorporeal membrane oxygenation for newborns with gastric rupture.
AB  - Extracorporeal membrane oxygenation (ECMO) has been recognized to be beneficial
      to overcome not only persistent pulmonary hypertension of the newborn, but also
      cardiopulmonary distress due to neonatal sepsis. However, few papers have
      reported on the efficacy of ECMO for surgical sepsis in neonates with underlying
      diseases. This paper reports our experience with ECMO in three newborns with
      gastric rupture, one of the most serious causes of surgical sepsis in the
      neonatal period. Over the past 12 years, 14 newborns had gastric rupture; 3
      developed lethal cardiopulmonary distress that conservative strategies, including
      aggressive intensive care, failed to manage, and were selected for ECMO. The
      clinical data of these patients were retrospectively analyzed. The onset time and
      duration of ECMO varied from 23 to 143 h of age and 72 to 294 h, respectively. In
      case 3, complicated by massive intra-abdominal hemorrhage during ECMO,
      anticoagulants were changed from heparin alone to combined use with nafamostat
      mesilate, a thrombin inhibitor with a very short half-life. Ultrafiltration or
      hemodialysis was added in two cases to regulate massive volume overload
      associated with renal failure. Despite major hemorrhagic complications in two
      cases, all patients survived. Thus, ECMO may be beneficial in managing neonates
      with therapy-resistant gastric rupture.

PMID- 11294266
TI  - Port-exteriorization appendectomy (PEA): a preliminary report.
AB  - Between 1994 and 1999, 121 patients with the clinical diagnosis of acute
      appendicitis were operated upon at our institute, 70 by conventional appendectomy
      and 51 by laparoscopic procedures. There were no significant differences in the
      demographic data, but the percentage of complicated appendicitis operated upon
      laparoscopically (47%) was higher than in those operated upon conventionally
      (35.6%). In 13 children a new laparoscopy-assisted technique was used, which
      entails exteriorization of the inflamed appendix via a right-iliac-fossa port and
      a complete appendectomy outside the abdominal cavity. The new technique proved to
      be useful in all types of appendiceal pathology; there were shorter operative
      times and hospital stays and it avoids the drawbacks associated with operating in
      complicated appendicitis.

PMID- 11294267
TI  - Colorectal perforations in neonates with anorectal malformations.
AB  - Colorectal perforations in neonates with anorectal malformations (ARM) are rarely
      reported. Two cases, one each with a low and high ARM is presented. Delayed
      patient presentation and "closed-loop" intestinal obstruction seem to be possible
      causes of perforation in these cases. Both patients survived following surgical
      intervention. The pertinent literature is reviewed to emphasize the overall
      management of such cases.

PMID- 11294268
TI  - Postanal sinus: single or different etiologies?
AB  - Experience with five patients who presented with a postanal sinus (PAS), all of
      which appeared to have a similar etiology at first hand, is reviewed. All
      patients were female and presented with a perianal fistula located in the midline
      posterior to the anus between the internal and external sphincter. All patients
      had a similar history and age at presentation (the 1st decade of life), which
      increased our assumption of a similar etiology. Further examinations revealed no
      internal connection to hollow organs or other pelvic structures, proving that the
      fistula was a sinus in all cases. One patient had a scimitar sacrum. In four
      cases the sinus was excised transanally, in one through a posterior sagittal
      approach. All patients had normal anal function postoperatively. Histologic
      examination was performed in all cases and showed results ranging from various
      types of epithelium to dermoid and epidermoid cysts, dismissing the theory of a
      similar etiology. In our opinion, a PAS can be a presenting sign for a variety of
      retrorectal developmental pathologies and should be differentiated from fistula
      in-ano.

PMID- 11294269
TI  - A computerized vector manometry and MRI study in children following posterior
      sagittal anorectoplasty.
AB  - The study was designed to evaluate computerized eight-channel vector manometry
      (8CVM) and pelvic floor magnetic resonance imaging (MRI) as methods to assess the
      anal sphincter following posterior sagittal anorectoplasty (PSARP) for anorectal
      malformations, in particular the functional capacity of the sphincter structures
      in correlation with postoperative MRI findings. Seventeen children had been
      operated upon for a rectovesical, -urethral, or -vaginal fistula including one
      female cloacal malformation; 4 had a secondary PSARP. Mean follow-up was 5.57
      years. Continence was evaluated with a modified Kelly score. A CVM technique with
      an eight-channel perfusion catheter was used. In addition to software-supported
      data, the manometric parameters included a score-system assessing three different
      pressure zones of the anal canal qualitatively on the three-dimensional image of
      the anal sphincter profile. The same procedure was performed on sagittal, oblique
      axial, and oblique coronal MRI. Furthermore, the thickness of the sphincter
      muscle was assessed at the level of the maximal mean segmental pressure. All
      children had decreased absolute vector-volumetry values at rest and on squeezing.
      Correlation with the clinical score was poor. Correlation of the manometric score
      with the clinical course was similar to the correlation of MRI score with
      clinical course (R = 0.425; P = 0.1). Thirteen children demonstrated normal or
      increased sphincter length; 5 of these had a decreased high-pressure zone (HPZ).
      The position of the anorectum in the sphincter muscles could be evaluated by the
      vector-volumetry image as anatomic in 11 cases, nearly correctly positioned in 4,
      and ectopic in 1 child. MRI detected 2 cases of malposition, 10 anatomic, and 4
      nearly-anatomic findings. Correlation of the manometric score with the MRI score
      and the thickness of the sphincter muscle at the HPZ was significantly high (R =
      0.801; P < 0.0001). 8CVM is thus highly sufficient in illustrating the function
      of the sphincter musculature seen on pelvic floor MRI. Both methods only
      moderately reflect clinical follow-up, since continence depends on more than
      sphincter ability.

PMID- 11294270
TI  - Multicystic dysplastic kidney detected by fetal sonography: conservative
      management and follow-up.
AB  - The most common cystic lesion recognized antenatally is multicystic dysplastic
      kidney (MCDK). Recently, conservative management without nephrectomy has been
      advocated. The purpose of this study was to report our experience in the
      conservative management of unilateral MCDK. Between 1989 and 1997, 20 children
      with MCDK detected by prenatal ultrasonography (US) were prospectively followed.
      At birth, US confirmed the prenatal findings in all cases. All patients were
      submitted to radioisotope scans and a micturating cystogram. Follow-up US
      examinations were performed annually. Mean age at diagnosis during the prenatal
      period was 31 weeks of gestation (range 24-38). Median follow-up time was 33
      months (range 7-91). Follow-up US was performed in 19 children; 13 (68%) showed
      partial involution, 4 (21%) complete involution, and 2 (11%) an increase in unit
      size. The mean age at complete or partial involution of the lesion was 18 months.
      No children developed hypertension or tumors, and all maintained normal growth.
      In conclusion, the natural history of MCDK is usually benign, and serial US
      examinations show that affected kidneys frequently show involution with time.

PMID- 11294271
TI  - Urethral trauma in children.
AB  - We report our 12-year experience in the management of urethral injuries in nine
      children, six boys and three girls. The most common mechanisms of injury were
      motor vehicle accidents, followed by straddle injuries. All the injuries in boys
      involved the anterior urethra, and in girls the proximal or mid-urethra. There
      were associated injuries in five, including three pelvic fractures. All children
      were investigated with a retrograde urethrogram. Four were treated non
      operatively with insertion of a urethral catheter. Of the remaining five, one had
      drainage of a penile haematoma, one cystourethroscopy, two insertion of urinary
      and suprapubic catheters, and one open cystotomy and passage of a guide wire with
      antegrade passage of a urethral catheter. Complications included one urinary
      tract infection, one urethral fistula, one urethrovaginal fistula, and two
      urethral strictures. Final outcome was satisfactory in all nine children.

PMID- 11294272
TI  - Reoperative orchiopexy: surgical aspects and functional outcome.
AB  - Over a 14-year period, a total of 40 patients underwent surgical revision after
      an unsuccessful orchiopexy attempt. Overall, 34 reorchiopexies (1 bilateral) and
      7 orchiectomies were performed. All reorchiopexies were carried out using
      extensive mobilization of the testis and spermatic cord. This approach was
      sufficient for scrotal placement of the testis in 23 instances; however, it was
      necessary to transpose the spermatic vessels medially in the remaining 11
      (incision of the transversalis fascia in 5, incision of the transversalis fascia
      and division of the inferior epigastric vessels in 6). Only 1 prepuberal boy
      developed testicular atrophy (2%). Functional long-term assessment was done in 20
      postpuberal patients using testicular ultrasound and sperm analysis. The
      reoperated cryptorchid testes were significantly smaller than the controls (P <
      0.005), but decreased fertility was only noted in 3 patients (18.7%). We conclude
      that testicular volume in adulthood is not directly related to fertility, so that
      accurate reorchiopexy seems to be the best way to preserve fertility in this
      special group of cryptorchid patients.

PMID- 11294273
TI  - Massive lower gastrointestinal hemorrhage caused by CMV disease as a presentation
      of HIV in an infant.
AB  - The gastrointestinal (GI) manifestations of acquired immunodeficiency syndrome in
      children are related to opportunistic infections like cytomegalovirus (CMV). CMV
      disease of the GI tract is a major cause of morbidity and mortality in
      immunocompromised patients: it typically produces mucosal ulcerations that can
      result in pain, bleeding, diarrhea, and GI perforation, often around the cecum.
      Preoperative diagnosis may be difficult, plain films and barium enema are often
      non-specific, and endoscopic evaluation is impossible when there is massive
      bleeding. The patient usually needs surgery to establish the correct diagnosis
      and initiate appropriate treatment. The use of gancyclovir for CMV disease in the
      postoperative period has improved the prognosis.

PMID- 11294274
TI  - Celiac disease presenting as entero-enteral intussusception.
AB  - Cramping abdominal pain with intermittent intestinal obstruction finally prompted
      investigation in a 4 1/2-year-old boy with severe failure to thrive (FTT). An
      entero-enteric intussusception was corrected, and celiac disease was identified
      as the cause of his inanition. Concomitant FTT and cramping abdominal pain should
      prompt investigation for celiac disease and small-bowel intussusception.

PMID- 11294275
TI  - Adrenocortical carcinoma in two female children.
AB  - Adrenocortical carcinoma is a rare tumor in children. This tumor is more likely
      to be hormonally active in children than in adults and tends to cause a variety
      of symptoms, which may mimic other benign endocrinopathies. These tumors are
      usually diagnosed at advanced stages and portend a dismal prognosis. We describe
      two cases of adrenocortical carcinoma. One child presented with Cushingoid
      symptoms secondary to hypercortisolism, including amenorrhea, hirsutism and
      weight gain. The other child presented with precocious puberty. Both children
      underwent resection of the tumors. We describe their presenting symptoms,
      postoperative course, adjuvant therapy and clinical course. Pertinent literature
      regarding the anatomy of the adrenal gland, pathology of adrenocortical
      carcinoma, factors influencing outcome, diagnostic modalities and treatment, are
      discussed.

PMID- 11294276
TI  - Ectopic scrotum and patent urachus.
AB  - Ectopic scrotum is a rare condition and has been reported in association with
      other urological abnormalities. We present a case with an associated patent
      urachus and a brief discussion on the possible mechanism to explain this
      deformation.

PMID- 11294277
TI  - Temporal dermoid--an unusual presentation.
AB  - It is rare for a frontotemporal dermoid cyst to present as a discharging sinus,
      and even more rare for it to have intracranial extensions. Only a few cases of
      intraorbital extension have been reported. We report a 14-month-old girl who
      presented with all the aforementioned features. She had a temporal dermoid with
      three discharging sinuses over the temporal area, lower lid, and cheek. It also
      had an intraorbital extension through the lateral orbital wall and an
      intracranial extension through the temporal bone. Preoperative computed
      tomography was done as there was a history of "orbital cellulitis". Excision of
      the cyst was done using a hemicoronal-preauricular incision. A lateral orbitotomy
      was required to remove the orbital component in continuity with the rest of the
      cyst.

PMID- 11294278
TI  - Long-term results of surgery for posterior urethral valves: a review.
AB  - Although the techniques for valve resection have been refined and the short-term
      management of patients with posterior valves has improved remarkably, there is
      growing concern about long-term outcome. Prenatal diagnosis has added to the
      urgency of predicting long-term outcome. This paper reviews all the important
      long-term data available with the aim of providing a concise picture for the
      reader, vis-a-vis long-term renal function, the role of proximal diversion in
      long-term outcome, bladder function and incontinence, the place of renal
      transplantation, prenatal diagnosis, intervention and prediction of renal
      function and sexual function and fertility.

PMID- 11294279
TI  - Use of a flexible illuminated stylet to demonstrate the proximal esophageal pouch
      in esophageal atresia.

PMID- 11294280
TI  - Hypertrophied muscle ring on the upper (gastric) end of the pylorus.

PMID- 11294281
TI  - Polyethylene glycol for button battery ingestion: a cautionary note.

PMID- 11294282
TI  - Bladder-neck repair in urinary bladder exstrophy.

PMID- 11294283
TI  - Bioartificial liver support.
AB  - Orthotopic liver transplantation is the only definitive therapy for patients with
      fulminant hepatic failure (FHF). However, due to shortage of organs, a large
      number of patients die before a liver can be procured for transplantation. In FHF
      the need for a liver is particularly urgent because of rapid deterioration in the
      patients' condition with the onset of cerebral edema and intracranial
      hypertension leading to irreversible brain damage. It is thus necessary to
      develop an extracorporeal liver support system to help maintain patients alive
      and neurologically intact until an organ becomes available for transplantation.
      Multiple attempts have been made, ranging from the use of plasma exchange to
      utilization of charcoal columns and extracorporeal devices loaded with liver
      tissue to develop liver support systems for treating patients with acute severe
      liver failure. None of these systems has achieved wide clinical use, and FHF due
      to multiple causes continues to be associated with significant morbidity and
      mortality. In this paper, the authors review the history of extracorporeal liver
      support for acute liver failure and discuss their experience with a hollow fiber
      bioartificial liver support system utilizing porcine hepatocytes in the treatment
      of patients with acute liver failure.

PMID- 11294284
TI  - Extreme discrepancy between macroscopic diagnosis and pathological findings of
      gallbladder cancer treated by hepatopancreatoduodenectomy.
AB  - Diagnosis of gallbladder cancer in terms of invasion depth and spread is an
      important factor in determining cumulative survival after surgical treatment.
      However, diagnostic methods available at present occasionally fail to judge
      staging correctly. We report a case of gallbladder cancer which showed extreme
      discrepancy between the preoperative macroscopic and imaging diagnosis (positive
      direct invasion to the liver and invasion to the bile duct and duodenum through
      the serosal layer; S3, Hinf3, Binf2, and stage IV by the Japanese Society of
      Biliary Surgery classification) and the pathological findings (limited in vasion
      within the subserosal layer; ss, hinf0. binf0, and stage II). This discrepancy
      allowed us to perform curative treatment by hepatopancreatoduodenectomy,
      including extended right lobectomy of the liver, external bile duct resection,
      resection of the mesocolon, and lymph node dissection. Surgeons should aim for
      curability of advanced gallbladder cancer by radical resection until accurate
      methods for the preoperative diagnosis of cancer spread are available, because
      the clinical picture may be modified by inflammatory changes.

PMID- 11294285
TI  - Villous tumor of the duodenum: report of a case and review of the literature.
AB  - Villous tumors of the duodenum are rare tumors which have been infrequently
      reported in the literature. Surgical treatment options include wide local
      excision and radical pancreaticoduodenectomy. A case of duodenal villous adenoma
      presenting with bilious vomiting is presented here.

PMID- 11294286
TI  - Mild hypothermia prevents cerebral edema in acute liver failure.
AB  - Mild hypothermia prevents the development of brain edema in rats with acute liver
      failure resulting from hepatic devascularization. Mechanistic studies performed
      in this model suggest that the protective effect of hypothermia results from the
      inhibition of blood-brain transfer of ammonia, an action which could result (at
      least in part) from an effect on cerebral blood flow. Hypothermia-induced
      reductions of brain ammonia are associated with normalization of extracellular
      brain glutamate concentrations in rats with acute liver failure. Studies in
      humans suggest that mild hypothermia is beneficial in the management of severely
      raised intracranial pressure, both before and after liver transplantation in
      patients with acute liver failure due to acetaminophen overdose. Mild hypothermia
      offers a potentially useful bridge therapy in patients with acute liver failure
      who are awaiting liver transplantation.

PMID- 11294287
TI  - Sepsis and cholestasis: basic findings in the sinusoid and bile canaliculus.
AB  - It is well known that the liver plays a major role in the clearance of systemic
      toxemia and is postulated as a regulational organ in the host-defense system. The
      well-controlled interaction between hepatic parenchymal cells and sinusoidal
      lining cells including macrophages and Kupffer cells can systematically regulate
      even critical infections. However, when patients are under the overload condition
      caused by severe infection, rejection of a transplanted liver and other hapatic
      dysfunction often are experienced following surgery. Among various signs and
      symptoms of hepatic dysfunction, progressive cholestasis is recognized as a
      polarized representation of the irreversible changes in hepatic constitutional
      cellular functions, especially in hepatic parenchymal cells. Bile canaliculi, the
      smallest components of the biliary tree, lie between the apical surfaces of
      adjacent hepatocytes. Septic cholestasis might be a result of disturbance of the
      total bile canalicular system, i.e., bile secretion, canalicular contraction, and
      so on. Recently, the molecular biology of the hepatocellular transport system has
      become better understood, and the pathophysiological condition of cholestasis can
      be explained as a representation of the intracellular molecular transcriptional
      system. Cellular changes in surgical cholestasis and molecular findings
      concerning the bile canaliculus are introduced in this article.

PMID- 11294288
TI  - Aspects of our liver support systems using extracorporeal xenoperfusion of pig or
      baboon liver: review.
AB  - Artificial liver support systems using xenoperfusion of pig or baboon liver have
      metabolic activity and there is the possibility that they could substitute for
      total liver functions; however, several problems have yet to be solved. In our
      early clinical experience, a method of cross-hemodialysis with interposed
      cuprophane membrane was employed in order to avoid immunological reactions in
      patients. Sixteen patients with hepatic failure were treated by this method.
      Although the coma grade was ameliorated in 65% of the patients, the ultimate
      survival rate was 18.9%. In this clinical trial, the indication for liver support
      was clarified based on hepatic mitochondrial functions. This unsatisfactory
      result could also be attributed to insufficient effects of the device, due to the
      interposed membrane, and also to damage of the supporting livers due to
      hyperacute xenoperfusion injury. Recent investigations in the field of
      xenotransplantations have shown us possibilities for controlling xenogeneic
      hyperacute rejection. Suppression of complement activation enabled long-term
      xenoperfusion of supporting livers with high metabolic activity. The
      administration of prostaglandin E1 or soluble complement receptor type 1, and the
      use of transgenic pig livers expressing human decay-accelerating factor, may be
      promising methods to establish highly active artificial liver support systems
      using xenoperfusion.

PMID- 11294289
TI  - Hepatocyte transplantation: new horizons and challenges.
AB  - Hepatocyte transplantation represents an alternative strategy for treating liver
      disease. Liver repopulation following acute liver failure could, potentially,
      eliminate the requirement for orthotopic liver transplantation. Similarly, the
      ability to repopulate the liver with disease-resistant hepatocytes offers new
      opportunities for correcting genetic disorders and treating patients with chronic
      liver disease. Recent advances concerning the fate of transplanted cells in the
      recipient liver, the efficacy of cell therapy in outstanding animal models of
      human disease. and the isolation of progenitor liver cells capable of
      differentiating into mature hepatocytes have renewed optimism in regard to
      treating people with hepatocyte transplantation. Recruitment of an increasing
      number of investigators to the field and the success of recent pilot studies
      indicate that hepatocyte transplantation will become routine clinical practice in
      the near future.

PMID- 11294290
TI  - Hepatocyte-based gene therapy.
AB  - Hepatocyte-based gene therapy may be used to replace a missing gene product,
      confer proliferating ability to cultured hepatocytes, prevent allograft
      rejection, massively repopulate the host liver, or grow xenogeneic hepatocytes in
      mammalian liver. Gene transfer into isolated hepatocytes can be accomplished via
      nonviral or viral vectors, the viral vectors being more useful at this time.
      Common recombinant viruses that integrate into the host genome include murine
      leukemia retroviruses and lentiviruses, adenoassociated virus, and the T-antigen
      deleted SV40 virus. Episomal viruses, such as adenoviruses, permit efficient gene
      transfer, but the transgene is lost upon proliferation of the transplanted
      hepatocyte in the host. Hybrid viruses that combine the high transduction
      efficiency of adenoviral vectors and the integrative capacity of other vectors,
      such as adenoassociated viruses, have been designed. Massive repopulation of the
      liver by transplanted hepatocytes can be achieved if a mitotic stimulus to the
      transplanted cells is combined with prevention of proliferation of the host
      hepatocytes. Treatment with a plant alkaloid or retrorsine, or preparative
      irradiation of the liver can be used to inhibit host hepatocellular
      proliferation, while partial hepatectomy, expression of Fas ligand, or thyroid
      hormone administration can be used as a mitotic stimulus to the transplanted
      cells.

PMID- 11294291
TI  - Is preoperative biliary drainage necessary according to evidence-based medicine?
AB  - Preoperative biliary drainage has been in use for a long time and is still being
      performed today in some institutions, but there has been a long-standing issue as
      to whether the necessity of this procedure has been proven medically. Many
      problems existed previously, such as systemic complications due to the difficulty
      in diagnosing and differentiating obstructive jaundice from jaundice left
      untreated for a long time, or surgeon-based problems such as a lack of surgical
      skill or undeveloped surgical techniques, or even inexperience in perioperative
      patient management. These problems, however, are being overcome with time, and
      the advantages of preoperative biliary drainage are now being questioned
      according to evidence-based medicine. Several recent controlled trials have
      clearly shown that preoperative biliary drainage is not necessary for lower bile
      duct obstruction, although it was noted that surgery after reduction of jaundice
      by percutaneous transhepatic cholangial drainage (PTCD) was very easily
      performed. It is important to understand that preoperative biliary drainage is
      unnecessary for lower bile duct obstruction, whether the technique follows a
      percutaneous approach, an endoscopic apporach, or stenting. Although it is still
      being debated, there have already been several reports regarding whether
      preoperative biliary drainage is necessary for upper bile duct obstruction, such
      as hilar bile duct carcinoma. This also needs to be clarified by randomized
      controlled trials. Aside from preoperative biliary drainage, the utilization of
      biliary drainage or stenting has been fully recognized as important for removing
      intrahepatic stones or choledochal stones, as well as for emergency drainage for
      acute cholangitis and for the treatment of unresectable malignant biliary
      stenosis. Additionally, percutaneous transhepatic cholangioscopy (PTCS), using
      the PTCD. or percutaneous transhepatic biliary drainage (PTBD) route. plays a
      major role not only in the removal of biliary stones but also in the diagnosis of
      cases in which it is difficult to differentiate between benign and malignant
      lesions.

PMID- 11294292
TI  - Hepatocyte growth factor: clinical implications in hepatobiliary pancreatic
      surgery.
AB  - Hepatocyte growth factor (HGF), originally identified as the most potent mitogen
      for hepatocytes, is now known to be a cytokine with numerous functions in a wide
      variety of cells. HGF transduces its various activities via a receptor encoded by
      the c-met proto-oncogene and coupled to a number of transducers integrating the
      HGF signal inside the target cells. Extcnsive investigation has revealed that HGF
      has various beneficial effects, especially for liver. HGF significantly
      stimulates regeneration in damaged, as well as in normal liver, ameliorates
      hepatic fibrosis/cirrhosis; and attenuates various types of liver dysfunction in
      animals. Moreover, the fascinating data on HGF in experimental liver and islet
      transplantation suggest that the use of HGF may represent a breakthrough for
      reducing the shortage of donor livers, and increasing the success rate of insulin
      independence after islet transplantation. Further understanding of the biological
      significance of HGF, including that in carcinogenesis, will undoubtedly have
      important clinical implications in hepatobiliary pancreatic surgery.

PMID- 11294293
TI  - Laparoscopic cholecystectomy via two ports, using the "Twin-Port" system.
AB  - We developed a "Twin-Port" system that allows a 5-mm camera and a forceps to be
      inserted through a single port for the laparoscopic cholecystectomy procedure. An
      infraumbilical incision of approximately 10mm is made to insert the "Twin-Port".
      After pneumoperitoneum is performed, a 5-mm camera and grasper are inserted to
      expose the gallbladder. A 5-mm trocar is inserted approximately 1 cm below the
      xiphoid process, and laparoscopic cholecystectomy is performed via two ports. The
      gallbladder is removed through the opened "Twin-Port". The operation was
      performed in 40 patients without acute inflammatory gallbladder disease. None of
      the patients required open abdominal surgery. In 3 patients, an additional 5-mm
      trocar was inserted because of difficulty in removing the gallbladder from the
      gallbladder fossa. Mean operation time was 49min. The size of the infraumbilical
      wound was almost the same as that with the conventional procedure using a 10-mm
      trocar. The "Twin-Port" system was devised to make laparoscopic cholecystectomy
      possible through two ports in the clinical setting. It may be less invasive than
      other LC procedures, and also has cosmetic and cost advantages. This procedure
      appears promising as a practical surgical treatment for cholecystolithiasis and
      gallbladder polyps.

PMID- 11294294
TI  - Prognostic factors after recurrence of resected hepatocellular carcinoma
      associated with hepatitis C virus.
AB  - To clarify the variables related to survival after recurrence of resected
      hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV), we
      studied 17 clinicopathological factors in 99 patients with recurrence of HCC
      associated with HCV infection after hepatic resection. The 1-, 3-, and 5-year
      survival rates after first resection in these patients were 91%, 81%, and 49%,
      while after recurrence they were 81%, 51%, and 29%, respectively. Multivariate
      analysis showed that the following six variables were independent prognostic
      factors after recurrence: platelet count, albumin level, bilirubin level, number
      of hepatic lesions, distant metastasis, and any treatment at recurrence. A
      correlation between second hepatic resection (SHR) and liver function tests was
      seen in regard to albumin and total bilirubin values at recurrence. Indeed,
      hepatic function and progression of intrahepatic tumors at recurrence were
      significant prognostic factors after recurrence of HCC associated with HCV
      infection, while any treatment at recurrence was also a significant prognostic
      factor. Therefore, in order to improve prognosis after recurrence, we should
      actively treat the recurrent hepatic lesions whenever possible.

PMID- 11294295
TI  - Treatment of ruptured undifferentiated sarcoma of the liver in children: a report
      of two cases and review of the literature.
AB  - Undifferentiated (embryonal) sarcoma of the liver (USL) is a highly malignant
      tumor of early life. Treatment choices for USL, especially with intraperitoneal
      rupture, are uncertain. Outcomes have been almost uniformly poor until recently.
      We describe two 7-year-old girls treated for ruptured USL. In the more recent
      patient, operative biopsy was followed by three cycles of cisplatin (CDDP),
      adriamycin (ADR), and cyclophosphamide (CPM). A fluid-filled cavity in the tumor
      showed enlargement and was drained. Two cycles of CDDP, ADR, vincristine (VCR),
      and ifosfamide were accompanied by reduction in tumor size, and trisegmentectomy
      was performed. She has no evidence of disease 3.5 years after surgery. In the
      other patient, left lobectomy was followed by a less intensive regimen, including
      CPM, VCR, and fluorouracil. This patient died of dissemination within 5 months.
      In 170 reported pediatric patients with USL, the 2-year disease-free survival was
      17%. For the 96 such patients reported since 1980, 2-year disease-free survival
      had improved to 27%. More aggressive chemotherapy has been associated with this
      change. Of 8 patients with tumor rupture whose details have been reported
      (including the 2 present patients) after resection of the tumor, 4 died, 1 was
      alive with disease, and 3 were free of disease at 8, 49, and 58 months,
      respectively, after diagnosis. Ruptured USL should be treated with combination
      chemotherapy including CDDP and ADR, as well as with curative resection.

PMID- 11294296
TI  - Choledochal cyst and benign stenosis of the main pancreatic duct.
AB  - We report here the first case of choledochal cyst associated with a benign
      stenosis of the cephalic part of the main pancreatic duct. The pancreatic ductal
      stenosis was associated with a protein plug located upstream of the stenosis.
      Preoperatively, it was not possible to rule out a localized intraductal
      pancreatic tumor, and a pylorus-preserving pancreaticoduodenectomy was performed.
      This association has not been described previously, and gives new insights into
      the pathogenesis of acute pancreatitis associated with choledochal cyst.

PMID- 11294298
TI  - Government evaluates distress of laboratory animals.

PMID- 11294297
TI  - Spontaneous necrosis of gallbladder carcinoma in patient with pancreaticobiliary
      maljunction.
AB  - While gallbladder carcinoma is occasionally associated with pancreaticobiliary
      maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein
      present a case of spontaneous necrosis of gallbladder carcinoma associated with
      direct invasion of viable cancer cell nests to the muscularis propria and
      subserosal layer located beneath the primary nodules. A 65-year-old Japanese man
      was admitted to a local hospital, complaining of repeated discomfort in the right
      hypochondrium. Ultrasonography and computed tomography scanning revealed
      cholecystitis associated with gallstones. Cholecystectomy was performed, and
      operative cholangiography demonstrated pancreaticobiliary maljunction. The
      resected gallbladder showed multiple mixed stones filled with necrotic debris and
      bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic
      nodules in the fundus, which were histologically confirmed to be necrotic
      remnants of a cancerous glandular structure. Small nests of papillary
      adenocarcinoma were found beneath the nodules in the muscularis propria and in
      the venous structure located in the connective tissues next to the divided margin
      of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the
      extrahepatic bile duct was then performed to remove the remaining cancerous
      tissues and/or micrometastasis in the liver and bile duct. The biliary tree was
      reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous
      lesions were found in the additionally resected specimens. This case indicates a
      unique morphological feature of gallbladder carcinoma associated with
      pancreaticobiliary maljunction, which provides some insight into the pathogenesis
      of spontaneous necrosis of gallbladder carcinoma.

PMID- 11294299
TI  - McIlwraith sees equine world topside and Down Under.

PMID- 11294301
TI  - Requests for explanation of acupuncture points.

PMID- 11294300
TI  - Opposing thoughts on acupuncture.

PMID- 11294302
TI  - Requests for explanation of acupuncture points.

PMID- 11294303
TI  - More views on complementary and alternative medicine.

PMID- 11294304
TI  - More views on complementary and alternative medicine.

PMID- 11294305
TI  - More views on complementary and alternative medicine.

PMID- 11294306
TI  - More views on complementary and alternative medicine.

PMID- 11294307
TI  - Comments on the value of pet health insurance.

PMID- 11294308
TI  - Debate on evolution won't be won in the JAVMA.

PMID- 11294309
TI  - Theriogenology question of the month. Differential diagnosis of ovarian tumor,
      ovarian hematoma and ovarian abscess.

PMID- 11294310
TI  - Employment of male and female graduates of US veterinary medical colleges, 2000.
AB  - Male graduates of veterinary medical colleges received a mean of 3.2 employment
      offers, compared with 2.8 offers received by female graduates. Overall, male
      graduates reported a mean starting salary of $38,786, compared with $37,148 for
      female graduates.

PMID- 11294311
TI  - Veterinary students and psychologic services.

PMID- 11294312
TI  - Comparison of the effects of morphine administered by constant-rate intravenous
      infusion or intermittent intramuscular injection in dogs.
AB  - OBJECTIVE: To compare physiologic and analgesic effects of morphine when given by
      IV constant-rate infusion or by IM injection to dogs undergoing laparotomy and to
      determine pharmacokinetics of morphine in dogs following IV constant-rate
      infusion. DESIGN: Prospective randomized controlled trial. ANIMALS: 20 dogs.
      PROCEDURE: Dogs undergoing laparotomy were treated with morphine beginning at the
      time of anesthetic induction. Morphine was administered by IV infusion (0.12
      mg/kg/h [0.05 mg/lb/h] of body weight) or by IM injection (1 mg/kg [0.45 mg/lb])
      at induction and extubation and every 4 hours thereafter. Treatments continued
      for 24 hours after extubation. RESULTS: Blood gas values did not indicate
      clinically significant respiratory depression in either group, and degree of
      analgesia (determined as the University of Melbourne Pain Scale score) and
      incidence of adverse effects (panting, vomiting, defecation, and dysphoria) were
      not significantly different between groups. Dogs in both groups had significant
      decreases in mean heart rate, rectal temperature, and serum sodium and potassium
      concentrations, compared with preoperative values. Mean +/- SEM total body
      clearance of morphine was 68 +/- 6 ml/min/kg (31 +/- 3 ml/min/lb). Mean steady
      state serum morphine concentration in dogs receiving morphine by constant-rate
      infusion was 30 +/- 2 ng/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that administration of morphine as a constant-rate IV infusion at a
      dose of 0.12 mg/kg/h induced effects similar to those obtained with
      administration at a dose of 1 mg/kg, IM, every 4 hours in dogs undergoing
      laparotomy. Panting was attributed to an opioid-induced resetting of the
      hypothalamic temperature set point, rather than respiratory depression.

PMID- 11294314
TI  - Combined hyponatremia and hyperkalemia mimicking acute hypoadrenocorticism in
      three pregnant dogs.
AB  - Differential diagnoses for hyponatremia with concurrent hyperkalemia should
      include hypoadrenocorticism. Renal failure, chylothorax, and gastrointestinal
      tract disorders may also cause abnormally low serum sodium:potassium ratios. The
      ACTH stimulation test is the gold standard for diagnosis of hypoadrenocorticism.

PMID- 11294313
TI  - Administration of charcoal, Yucca schidigera, and zinc acetate to reduce
      malodorous flatulence in dogs.
AB  - OBJECTIVE: To determine whether feeding activated charcoal, Yucca schidigera, and
      zinc acetate would ameliorate the frequency and odor characteristics of
      flatulence in dogs. DESIGN: In vitro screening of active agents followed by a
      randomized controlled trial. ANIMALS: 8 adult dogs. PROCEDURE: A fecal
      fermentation system was used to assess the effects of activated charcoal, Yucca
      schidigera, and zinc acetate alone and in combination on total gas production and
      production of hydrogen sulfide, the primary determinant of flatus malodor in
      dogs. All 3 agents were subsequently incorporated into edible treats that were
      fed 30 minutes after the dogs ate their daily rations, and the number, frequency,
      and odor characteristics of flatulence were measured for 5 hours, using a device
      that sampled rectal gases and monitored hydrogen sulfide concentrations. RESULT:
      Total gas production and number and frequency of flatulence episodes were
      unaffected by any of the agents. Production of hydrogen sulfide in vitro was
      significantly reduced by charcoal, Yucca schidigera, and zinc acetate by 71, 38,
      and 58%, respectively, and was reduced by 86% by the combination of the 3 agents.
      Consumption of the 3 agents was associated with a significant decrease (86%) in
      the percentage of flatulence episodes with bad or unbearable odor and a
      proportional increase in the percentage of episodes of no or only slightly
      noticeable odor. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that
      activated charcoal, Yucca schidigera, and zinc acetate reduce malodor of flatus
      in dogs by altering the production or availability of hydrogen sulfide in the
      large intestine.

PMID- 11294315
TI  - Safety, efficacy, and immunogenicity of a modified-live equine influenza virus
      vaccine in ponies after induction of exercise-induced immunosuppression.
AB  - OBJECTIVE: To determine safety, efficacy, and immunogenicity of an intranasal
      cold-adapted modified-live equine influenza virus vaccine administered to ponies
      following induction of exercise-induced immunosuppression. DESIGN: Prospective
      study. ANIMALS: Fifteen 9- to 15-month old ponies that had not had influenza.
      PROCEDURE: Five ponies were vaccinated after 5 days of strenuous exercise on a
      high-speed treadmill, 5 were vaccinated without undergoing exercise, and 5 were
      not vaccinated or exercised and served as controls. Three months later, all
      ponies were challenged by nebulization of homologous equine influenza virus.
      Clinical and hematologic responses and viral shedding were monitored, and serum
      and nasal secretions were collected for determination of influenza-virus-specific
      antibody isotype responses. RESULTS: Exercise caused immunosuppression, as
      indicated by depression of lymphocyte proliferation in response to pokeweed
      mitogen. Vaccination did not result in adverse clinical effects, and none of the
      vaccinated ponies developed clinical signs of infection following challenge
      exposure. In contrast, challenge exposure caused marked clinical signs of
      respiratory tract disease in 4 control ponies. Vaccinated and control ponies shed
      virus after challenge exposure. Antibody responses to vaccination were restricted
      to serum IgGa and IgGb responses in both vaccination groups. After challenge
      exposure, ponies in all groups generated serum IgGa and IgGb and nasal IgA
      responses. Patterns of serum hemagglutination inhibition titers were similar to
      patterns of IgGa and IgGb responses. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that administration of this MLV vaccine to ponies with exercise-induced
      immunosuppression was safe and that administration of a single dose to ponies
      provided clinical protection 3 months later.

PMID- 11294316
TI  - Intragastric pH in critically ill neonatal foals and the effect of ranitidine.
AB  - OBJECTIVE: To characterize intragastric pH profiles in critically ill foals and
      determine whether administration of ranitidine altered pH profiles. DESIGN:
      Prospective observational study. ANIMALS: 23 hospitalized neonatal foals < or = 4
      days of age. PROCEDURE: Intragastric pH was measured continuously for up to 24
      hours by use of an indwelling electrode and continuous data recording system. In
      21 foals, ranitidine was administered IV. RESULTS: 10 foals had predominantly or
      exclusively alkaline profiles, 10 had profiles typical of those reported for
      healthy foals, with periods of acidity (hourly mean pH < 5.0 at least once), and
      3 had atypical profiles with periods of acidity. All 10 foals that had
      intragastric pH profiles typical of healthy foals survived, whereas only 2 foals
      with alkaline profiles survived, and none of the foals with atypical profiles
      survived. The effects of ranitidine administration could not be assessed in 13
      foals because of a high baseline intragastric pH. In 7 of the remaining 9,
      ranitidine administration resulted in an alkalinizing response, but this response
      was often of blunted duration. Ranitidine administration did not appear to alter
      the intragastric pH profile in the remaining 2 foals. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that hospitalized critically ill foals often have
      intragastric pH profiles different from those reported for healthy foals and may
      respond differently to ranitidine administration than do healthy foals. Many
      critically ill foals have continuously alkaline intragastric pH profiles,
      questioning the need for prophylactic administration of ranitidine in all
      critically ill foals.

PMID- 11294317
TI  - Evaluation of a balanced fresh paste diet for maintenance of captive neotropical
      rattlesnakes used for venom production.
AB  - OBJECTIVE: To evaluate efficacy of a balanced fresh paste diet for maintenance of
      captive neotropical rattlesnakes used for venom production. DESIGN: Controlled
      clinical trial. ANIMALS: 40 healthy neotropical rattlesnakes. PROCEDURE:
      Rattlesnakes were force-fed once per week (10% of body weight) for 19 weeks; 20
      control snakes received dead mice, whereas 20 test snakes received a balanced
      fresh paste diet. Ecdysis rates were calculated, and body weight was recorded
      weekly. After 19 weeks, venom was extracted and analyzed. RESULTS: Sickness or
      deaths were not observed; weight loss during ecdysis and weight gain overall were
      similar between groups. Snakes fed the balanced fresh paste diet had similar
      ecdysis frequency, venom potency, and protein concentration in venom as did
      snakes fed mice. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a
      balanced fresh paste diet has sufficient nutritional value to avoid weight loss
      and death and does not adversely affect venom quality in captive neotropical
      rattlesnakes.

PMID- 11294318
TI  - Morphologic and cytochemical characteristics of blood cells and hematologic and
      plasma biochemical reference ranges in green iguanas.
AB  - OBJECTIVE: To determine blood cell morphologic characteristics and hematologic
      and plasma biochemical reference ranges for iguanas housed in a warm indoor and
      outdoor environment with regular exposure to direct sunlight. DESIGN: Original
      study. ANIMALS: 51 clinically normal iguanas (18 males, 25 females, and 8
      juveniles) housed in 3 Florida locations. PROCEDURE: Blood was collected from the
      coccygeal or ventral abdominal vein. Any samples that had obvious hemolysis or
      clot formation were not used. Leukocyte counts were determined manually; other
      hematologic values were obtained by use of a commercially available cell counter.
      Plasma biochemical values were determined by use of a spectrophotometric
      chemistry analyzer. Blood smears were stained with Wright-Giemsa and cytochemical
      stains for morphologic and cytochemical evaluation. RESULTS: Hematologic ranges
      were generally higher in this study than previously reported. Thrombocytes were
      variable in appearance between individuals and sometimes difficult to distinguish
      from lymphocytes on a Wright-Giemsa preparation. Concentrations of calcium,
      phosphorus, total protein, globulins, and cholesterol were significantly higher,
      and the albumin:globulin ratio was significantly lower, in healthy gravid females
      than in male or nongravid female iguanas. Nongravid females had significantly
      higher calcium and cholesterol concentrations, compared with males. The
      calcium:phosphorus ratio was > 1 in all iguanas. Gravid females had a calcium
      phosphorus product ranging between 210 and 800. Intracytoplasmic inclusions were
      identified within the erythrocytes of some iguanas. CONCLUSIONS AND CLINICAL
      RELEVANCE: Hematologic ranges for iguanas in this study are higher than those
      reported for iguanas. Sex and age of the iguana should be considered when
      evaluating biochemical values. Healthy ovulating and gravid females may have
      significantly increased electrolyte and protein concentrations, but maintain a
      calcium:phosphorus ratio > 1.

PMID- 11294319
TI  - Occupational health--an overview.

PMID- 11294320
TI  - Occupational health in India--current and future perspective.

PMID- 11294321
TI  - Diagnostic potential of histochemical demonstration for copper-orcein stain.
AB  - The histochemical demonstration of hepatic copper is important in the diagnosis
      of paediatric copper storage disorders. Conflicting results have been published
      regarding ability of different histochemical stains to demonstrate copper storage
      in the liver. Hence the authors retrospectively analysed eighty-two liver
      biopsies from 82 patients of Indian childhood cirrhosis (ICC), 59 males and 23
      females aged between 1-4 years (mean age 3.1 years). All cases were stained with
      orcein stain. On the basis of histological picture the liver biopsies were
      divided into the three histological grades I, II and III. Orcein positively was
      graded from I to IV. All cases showed positivity with orcein stain. Most cases
      showed grades II and III of orcein positivity. The association between
      histological and orcein grades was significant. The present study demonstrates
      the diagnostic utility of orcein stain in liver copper storage disorder, Indian
      childhood cirrhosis. Variable copper content in the same histological grade of
      the disease could be due to individual factors such as genetic milieu which
      determine the amount of copper liver can store without toxicity.

PMID- 11294322
TI  - Needle stick injuries among medical students.
AB  - Questionnaires were distributed among 200 medical students regarding safety
      precautions observed while perfonning various invasive procedures during their
      clinical posting. Only 106 students responded with the completed questionnaire.
      The most common procedure performed by the students was drawing of blood, with an
      average frequency of 60.8 per month. Sixty-one per cent of the students reported
      being injured during the various procedures and only 3 5.5% of them used gloves.
      Resheathing the needle was responsible for causing injury to 69% of the students,
      which was significantly higher than injuries occurring while entry into the vein
      or withdrawing the needle (p<0.05).

PMID- 11294323
TI  - Occupational health problems among agricultural and plantation workers.
AB  - Agricultural and plantation works are associated with a variety of unique
      occupational health hazards in the form of physical factors like extreme weather
      conditions, sunrays, etc; chemicaVtoxicological hazards in the form of
      pesticides/fertilisers, etc, including different forms of biological and
      mechanical hazards. As most of our rural people are engaged in varied types of
      agricultural activities, they are highly susceptible for suffering from numerous
      work related health disorders. There are very few data regarding the epidemiology
      of occupational health disorders among agricultural and plantation workers.
      Clinically well recognised group of occupationally acquired health problems may
      be respiratory, dermatological, traumatic, poisoning and neoplastic in nature.
      Prevalence of some specific zoonotic diseases and behavioural health problems are
      also found to be more among them. There is lack of attention for prevention and
      control of these occupational health problems. An adequately developed
      comprehensive occupational health care programme having all the components of
      preventive, curative and rehabilitative aspects can only promote and maintain the
      highest degree of physical, mental and social well-being in all types of
      agricultural and plantation workers of rural India.

PMID- 11294324
TI  - Occupational health surveillance in the chemical industry.
AB  - Health surveillance has its well defined place within occupational health care.
      Only a few functions are specific to the chemical industry. Occupational health
      surveillance used to be targeted at the early detection of occupational illnesses
      (secondary prevention) but other purposes have gained importance in recent years:
      ensuring the fitness of every worker for his or her job, promoting workers'
      health in general, contributing to the safety of the plant operation by
      identifying workers whose behaviour is likely to endanger others, contributing to
      product quality by assisting in the fulfilment of good manufacturing practice
      requirements, etc. If the occupational physician wants to maintain his role as
      key player in protecting workers' health, he must get involved in the important
      activities of primary prevention contributing directly to workplace improvements.
      Such improvements can only be based on systematic assessments of the workplaces.
      These assessments again provide the necessary objective basis to structure health
      surveillance in a way that takes into account the possible adverse effects coming
      from the workplace.

PMID- 11294325
TI  - Mortality in acute aluminium phosphide poisoning having hypomagnesaemia with and
      without ECG changes.
AB  - Acute aluminium phosphide poisoning produces hypomagnesaemia with or without ECG
      changes. The mortality rate is significantly higher in those patients with
      hypomagnesaemia who have ECG changes.

PMID- 11294326
TI  - Substance abuse by medical students and doctors.
AB  - The doctors are vulnerable to substance abuse/addiction due to their ready
      accessibility to the substances of abuse. There is higher percentage use of
      alcohol, tranquillisers and psychedelics among medical students, and dependence
      rates are 5% for medical students and 3% for doctors. Majority of the substance
      abusing doctors are graduates, belong to medicine speciality (21%) and majority
      of them prescribe drugs to themselves (37%). The consultants experience more
      substance related complications, despite having late age of onset of alcohol and
      substance dependence, less number of concomitant substance abuse and less career
      handicap. Stress (situational, personal and professional), medical student abuse
      and family history of alcoholism are the major risk factors. Despite paucity of
      studies in Indian population, substance use is reported between 32.5% to as high
      as 81.2% among medical students, intems and house physicians. In spite of the
      treatment dilemmas, the physicians do respond favourably to treatment. These
      findings have implications in planning preventive and interventional strategies
      for this professional group.

PMID- 11294327
TI  - Need for research on health hazards due to noise pollution in metropolitan India.
AB  - Noise has ill effects tagged to its definition; yet, even though pollution of the
      air, water and land in metropolitan India has attracted some recognition, little
      attention has been paid to noise pollution and its effects. Noise acts upon the
      body very much as other stresses do and so its effects are far reaching affecting
      not just hearing but other body functions too. This article tries to generate
      some interest and controversies on the subject to initiate more action on noise
      pollution.

PMID- 11294328
TI  - A presumptive case of lead poisoning in a brass-worker's child.
AB  - A one-year-old male child was admitted with the complaints of vomiting and
      irritability for 4 days, haematemesis and melaena for one day and had generalised
      tonic convulsions on the day of admission. Examination revealed exaggerated
      reflexes with group II coma. Blood film showed basophilic shippling. Straight x
      ray showed lead lines in the metaphyses of ribs, humerii, scapulae, iliac crests
      and upper ends of femurs. The boy's father was an employee of brass industry
      where brass alloys used cotained lead in substantial amount. A presumptive case
      of lead poisoning (as diagnosed) was treated symptomatically. Chelating agent was
      called for but the patient left. In the present case the hands of the child were
      contaminated with lead dust brought home by his father either in person or in
      clothings. The child used his hands constantly in his mouth to get poisoned by
      lead.

PMID- 11294329
TI  - Recurrent femoral pseudoaneurysm following intravenous opioid abuse: a case
      report.
AB  - Long term intravenous drug abuse is associated with recurrent femoral
      pseudoaneurysm in a 36-year-old man. The clinical features alongwith a suitable
      discussion is described in this case report.

PMID- 11294330
TI  - Successful management of hypokalaemia related conduction disturbances in acute
      aluminium phosphide poisoning.
AB  - A case of acute aluminium phosphide poisoning is described, who presented in
      shock secondary to electrolyte related cardiac rhythm disturbance and the
      judicious correction of the same could save his life without any consequence.

PMID- 11294331
TI  - Methaemoglobinaemia in epidemic proportions.
AB  - Five cases of methaemoglobinaemia, following exposure to industrial waste, are
      examined, investigated and managed successfully. The condition is discussed in
      detail.

PMID- 11294332
TI  - The value of the right chest leads in electrocardiogram.

PMID- 11294335
TI  - Statistics for medical students and doctors.

PMID- 11294334
TI  - CPA and role of IMA members.

PMID- 11294333
TI  - Spurious drugs.

PMID- 11294336
TI  - Unilever's environmental strategy. Interview with Antony Burgmans, co-chairman of
      Unilever, on its environmental strategy.

PMID- 11294337
TI  - Occupational health in Unilever--a strategic approach.

PMID- 11294338
TI  - Use of anafortan intravenous injection for treatment of colicky pain.

PMID- 11294339
TI  - Time flies: investigating the connection between intrinsic motivation and the
      experience of time.
AB  - The present study investigated the relationship between intrinsic motivation and
      the subjective experience of time passing. The Work Preference Inventory, which
      measures trait intrinsic and extrinsic motivation, was administered to 75
      undergraduate participants. Measures of time awareness, time estimation, checking
      of time, and perceived speed of time were collected using the experience sampling
      method. Participants carried electronic schedulers for five days and completed
      questionnaires each time the scheduler sounded (eight times per day). Results
      showed that higher intrinsic motivation was associated with checking and thinking
      about time less often, a subjective experience of time passing more quickly, and
      more of a tendency to lose track of time. The experience of time awareness was
      accompanied by a subjective sense of time moving slowly, a tendency to
      overestimate the time, and a more negative affective experience. These findings
      suggest that time perception is an important dimension of motivational
      experience.

PMID- 11294340
TI  - The predictive strength of personal constructs versus conventional constructs:
      self-image disparity and neuroticism.
AB  - Idiographic personal construct (PC) measures of self-image disparity were
      hypothesized to be stronger than nonidiographic conventional construct (CC)
      measures in predicting neuroticism. Ninety-six college students completed PC and
      CC measures of real self, ideal self, social self, and ideal social self; the NEO
      Five-Factor Inventory; and the Marlowe-Crowne Social Desirability Scale. Content
      analysis showed that individuals' PC measures were unique. The disparity between
      real self and ideal self and the disparity between social self and ideal social
      self were computed for PC and CC; test-retest reliabilities were .76 to .81.
      Results of simultaneous multiple regression analyses supported the hypothesis.
      Also, the two-variable PC self-image disparity scores were stronger than one
      variable PC esteem scores in predicting neuroticism. Implications were discussed
      for research method, self-concept theory, personal construct theory, neuroticism,
      and psychotherapy.

PMID- 11294341
TI  - Predicting depression from temperament, personality, and patterns of social
      relations.
AB  - The present study used a levels-of-analysis perspective (McAdams, 1995) to link
      temperament to depression. We hypothesized a mediational role for three
      personality variables (Agreeableness, Extraversion, Neuroticism) and two
      interpersonal variables (social support and negative social exchange) in
      channeling the effects of temperament. A structural equation modeling approach
      supported the hypothesis that these three personality variables were mediators of
      the link between temperament and depression. The patterns of mediation differed
      for Agreeableness, Extraversion, and Neuroticism. In addition to the three
      personality variables, social support and negative social exchange were also
      found to mediate the effects of temperament. There was no evidence that patterns
      of relations among the variables differed between males and females. Results are
      discussed in terms of a levels-of-analysis approach to the examination of the
      effects of temperament and personality on adaptation outcomes.

PMID- 11294342
TI  - Assessing future possible selves by gender and socioeconomic status using the
      anticipated life history measure.
AB  - This is a report from the first phase of a longitudinal study of the ways young
      adults imagine their future lives. The future possible selves of 223 18- and 19
      year-old adults were examined using the Anticipated Life History measure (ALH), a
      psychological instrument prompting participants to describe their future life
      course from their 21st birthday until their death. When the ALH narratives were
      coded for presence/absence of life events, female participants were more likely
      to predict career choice, marriage, children, divorce, and death of spouse than
      their male counterparts; when coded for psychological qualities, female
      participants demonstrated greater psychological complexity and awareness of
      future life role choices and conflicts. Participants with lower SES wrote ALH
      narratives with fewer altruistic acts, less awareness of life role complexity,
      and fewer anticipated conflicts and their resolutions than those with higher SES.

PMID- 11294343
TI  - Adult generativity and the socialization of adolescents: relations to mothers'
      and fathers' parenting beliefs, styles, and practices.
AB  - Mothers, fathers, and their adolescent children participated in two studies
      investigating the relations between Erikson's concept of generativityin adulthood
      and patterns of parenting. Study 1 involved 77 mothers and 48 fathers of 1st-year
      university students; Study 2 was part of an investigation of socialization
      processes in 35 families with an adolescent, aged 14-18. Parental generative
      concern was assessed by the Loyola Generativity Scale (LGS) of McAdams and de St.
      Aubin (1992) in each study. In both studies, mothers demonstrated positive
      relations between scores on the LGS and an authoritative style of parenting, as
      well as between generativity and more positive, optimistic views of adolescent
      development. In Study 2, these more positive views in turn mediated some aspects
      of autonomy-fostering practices used with the adolescent. Variations in fathers'
      levels of generative concern were less consistently related to these indices of
      parenting, however.

PMID- 11294344
TI  - Report from the 7th meeting of CEN/TC 275/WG 6 "food analysis, horizontal methods
      -microbial contamination", Vienna 13th June 2000.

PMID- 11294345
TI  - Report from the 20th meeting of ISO/TC 34/SC 9 "Agricultural and Food Products-
      Microbiology", Vienna--14/16 June 2000.

PMID- 11294347
TI  - On the need for another type of predictive model in structured foods.
AB  - Most of the models discussed up till now in predictive microbiology do not take
      into account the variability of microbial growth with respect to space. In
      structured (solid) foods, microbial growth can strongly depend on the position in
      the food and the assumption of homogeneity can thus not be accepted: space must
      be considered as an independent variable. Indeed, experimental evidence exists of
      bacteria competition on agar not showing the same behavior as the competition in
      a well-mixed liquid culture system. It is conjectured that this is due to the
      spatially structured habitat. Therefore, in the current paper, a prototype two
      species competition model proposed in previous work by the authors is extended to
      take space into account. The extended model describes two phenomena: (i) local
      evolution of biomass and (ii) transfer of biomass through the medium. The
      structure of the food product is taken into account by limiting the diffusion
      through the medium. The smaller mobility of the micro-organisms in solid foods
      allows spatial segregation which causes pattern formation. Evidence is given for
      the fact that taking space into account indeed has an influence on the behavior
      (coexistence/extinction) of the populations. Although the reported simulations
      are by no means to be interpreted as accurate predictions, the proposed model
      structure allows one to highlight (i) important characteristics of microbial
      growth in structured foods and (ii) future research trends in predictive
      microbiology.

PMID- 11294346
TI  - Characterization of south african isolates of Salmonella enteritidis by phage
      typing, numerical analysis of RAPD-PCR banding patterns and plasmid profiles.
AB  - Eleven of the 33 strains of Salmonella enteritidis (S.E.) included in this study
      belonged to phage type 34. Six strains belonged to phage type 14, six strains to
      phage type 4 and four strains to phage type 7. The remaining six strains belonged
      to phage types 35, 1, 24var (a variation of phage type 24), 9a, 1b and an unknown
      phage type. The majority of S.E. phage type 34 strains (eight of the 11) grouped
      at R2 > or =0.45 into one RAPD-PCR cluster with two strains of phage types 4, a
      strain of phage type 24var and a strain of phage type 9a, indicating that they
      consist of a genetically heterogeneous collection of strains. Two of the
      remaining three phage type 34 strains grouped into two different clusters, well
      separated from the other phage type 34 strains. One strain of phage type 34 was
      genetically diverse and did not cluster with any of the strains included in this
      study. Three of the phage type 14 strains grouped into cluster 11 at R2 > or
      =0.72, suggesting that they are genetically closely related. However, the
      remaining three strains of phage type 14 grouped into two separate clusters.
      Strains of phage types 7, 35, and 1 grouped in one cluster at R2 > or = 0.55. Our
      results clearly indicated that S.E. strains of the same phage type are not always
      genetically related. On the other hand, strains of a high genetic relatedness
      classified as different phage types. No specific plasmid profile could be linked
      to any of the phage types. Based on results obtained by LD50 virulence tests,
      strains containing the 38 MDa plasmid are more virulent compared to strains which
      do not contain the plasmid.

PMID- 11294348
TI  - Selection and characterization of mixed starter cultures for lactic acid
      fermentation of carrot, cabbage, beet and onion vegetable mixtures.
AB  - An evaluation of various lactic acid bacteria (LAB) for the fermentation of
      cabbage, carrot and beet-based vegetable products was carried out. As part of a
      screening process, the growth of 15 cultures in a vegetable juice medium (VJM)
      was characterized by automated spectrophotometry. Acidification patterns as well
      as viability during storage of the LAB were also established. There were greater
      differences between the pure cultures than the mixed ones with respect to growth
      in VJM and viability during storage. Reductions in viable cell counts during
      storage of the fermented VJM occurred more rapidly with a Leuconostoc strain than
      for pediococci or lactobacilli. Inoculation of vegetables was carried out with
      cultures of Lactobacillus plantarum NK-312, Pediococcus acidilactici AFERM 772
      and Leuconostoc mesenteroides BLAC which were rehydrated in a brine. This
      rehydration procedure was not detrimental to viability. During fermentation of a
      carrot/cabbage vegetable mix, sugar metabolism was characterized by the
      assimilation of both glucose and fructose, but sugars remained in the fermented
      vegetables when acidification stopped. The pH in the LAB-inoculated vegetables
      after 72 h at 20 degrees C was significantly lower (by 0.2 units) than the
      uninoculated control. Inoculation with LAB designed for silage fermentation
      resulted in the inhibition of acetic acid production, and reduced the production
      of ethanol during fermentation. The selection process on VJM enabled the
      preparation of a mixed culture that was more rapid than the silage inoculants in
      acidifying the medium and was more effective in reducing the production of gas
      during the fermentation and storage of the fermented vegetables.

PMID- 11294349
TI  - Growth and metabolic activity of Shewanella putrefaciens maintained under
      different CO2 and O2 concentrations.
AB  - Growth, trimethylamine (TMA), off-odour and biogenic amine production by a strain
      of Shewanella putrefaciens isolated from spoiled hake (Merlucius merluccius L.)
      and cultured in a model system, were tested under four different gas compositions
      (60% CO2/40% O2, 60% CO2/15% O2/25% N2, 40% CO2/60% O2, 40% CO2/40% O2/20% N2)
      and under air. After 3 weeks of incubation, the control (air) batch showed the
      highest microbial counts (> 9 log cfu/ml) and TMA concentrations (45 mg N-TMA/100
      ml), and strong putrid off-odours were detected from day 15. High amounts of
      putrescine and cadaverine were produced in this batch, but histamine increased
      only slightly. Batches under controlled atmospheres showed reduced growth, TMA,
      off-odour and biogenic amine production. The 40% CO2/60% O2 mixture had the
      strongest inhibitory effect on bacterial growth, while the 60% CO2/15% O2/25% N2
      mixture was less effective. Putrescine and histamine production was lowest in S.
      putrefaciens under the 40% CO2/60% O2 mixture. However, the level of histamine in
      S. putrefaciens was higher under 40% CO2/40% O2/20% N2 than when the bacteria was
      incubated in air. Under the gas mixtures, there was a similar decrease in the
      production of cadaverine and agmatine by S. putrefaciens, irrespective of the gas
      concentrations. The production of 2-phenylethylamine appeared to be inhibited
      under any atmospheric condition.

PMID- 11294350
TI  - Reaction kinetic interpretation of heat destruction influenced by environmental
      factors.
AB  - Based on reaction kinetics and thermodynamic considerations a mathematical model
      was developed to describe the thermal death rate of microbes as a function of
      environmental factors such as temperature, water activity, pH and redox
      potential. The mathematical model is discussed and validated by fitting to data
      sets of heat destruction of Lactobacillus brevis and Lactobacillus plantarum. The
      mathematical analysis of the kinetic model and the parameters of the model
      fitting demonstrate its applicability both for the prediction of the heat
      destruction rate and estimation of the thermodynamic parameters of heat
      destruction.

PMID- 11294351
TI  - Validation of ISO method 11290 part 1--detection of Listeria monocytogenes in
      foods.
AB  - The European and International Standard method for the detection of Listeria
      monocytogenes, described in EN ISO 11290 Part 1: 1997 (International Organisation
      for Standardisation, Geneva) was validated by order of the European Commission
      (Standards, Measurement and Testing Fourth Framework Programme Project SMT4-CT96
      2098). Nineteen laboratories in 14 countries in Europe participated in a
      collaborative trial to determine the performance characteristics of the method,
      which are intended for publication in the corresponding standard. An additional
      objective of this project was to devise a new series of parameters to indicate
      the 'precision' of microbiological qualitative methods. The method was challenged
      with three food types, namely fresh cheese, minced beef and dried egg powder and
      a reference material. Inoculation levels ranged from 5 to 100 cfu/25 g. Each
      participant examined five replicates of each food type at three inoculum levels
      and five reference materials. Both PALCAM and Oxford media were assessed. All
      test materials were subjected to stringent homogeneity and stability testing
      before being used in the collaborative trial. The results demonstrated that the
      method prescribed in EN ISO 11290-1 had an overall sensitivity of 85.6% and a
      specificity of 97.4%. L. monocytogenes was detected in most cases after primary
      enrichment, although secondary enrichment often yielded further positives.
      However, a significant number of false-negative results were obtained with all
      food types when large numbers of L. innocua were present in the test materials.
      L. innocua tended to dominate L. monocytogenes during the selective enrichment
      stages and thus masked small numbers of colonies of L. monocytogenes on the
      isolation media. There was no evidence from this collaborative study to
      demonstrate a significant difference in performance between Oxford and PALCAM
      media. Due to the problem of false-negative results with this method as
      highlighted in this trial, recommendations have been made to ISO to launch a
      revision of the standard to improve the detection of low numbers of L.
      monocytogenes in foods. New statistical methods devised to advance the
      measurement of the performance of qualitative microbiological methods are also
      described.

PMID- 11294352
TI  - Oral inoculation with Gymnorhynchus gigas induces anti-parasite anapyhylactic
      antibody production in both mice and rats and adverse reactions in challenge
      mice.
AB  - This study was performed to mimic human consumption of fish flesh infected with
      larvae of the fish cestode Gymnorhynchis gigas and examine possible side effects
      thereof. Both a rat and a mouse G. gigas oral inoculation model were used. The
      rat model was evaluated according to propensity to induce stress responses in
      three tissues and anaphylactic antibody production. The mouse model measured anti
      G. gigas IgG, M and A (H + L) levels in intestinal fluids, fecal suspensions and
      serum and specific serum IgE levels by enzyme-linked immunosorbent assay.
      Additionally, biological activity of anaphylactic antibodies in test mice and
      rats were evaluated utilizing challenge reinoculation(s) and intradermal skin
      testing, respectively. With the rat inoculation model, we noted both occurrence
      of a shock response, viz. increased expression of heat shock proteins in
      intestine and spleen, and of immediate-type skin reactions. No positive wheals
      were seen on skin sites treated with PBS or soluble Trichinella spiralis extract.
      With the mouse model, our results showed that all body fluids tested had
      significantly more anti-G. gigas IgG, M and A (H + L) than their counterparts
      from either PBS-treated or T. spiralis-infected controls. In addition, the mouse
      G. gigas model had significantly higher specific serum IgE. When challenged by
      oral route all test mice (n = 5) manifested immediate-type signs of distress.
      Repeated exposure to the "allergen", produced clinical signs appearing more
      rapidly and persisting longer. These findings suggest that feeding on fish
      infected with G. gigas plerocercoids triggers the production of anaphylactic-type
      antibodies in both rats and mice and, by implication, possibly also in humans.

PMID- 11294353
TI  - Stochastic modelling of the growth of a microbial population under changing
      temperature regimes.
AB  - The application of models of microbial growth to the design of food safety
      systems requires consideration of the effect of arbitrary changes in external
      variables on growth of bacteria. In particular, the effect of changes in external
      variables, such as temperature, on the probability that the microbial population
      size will not exceed acceptable levels at a given time needs to be predicted.
      This paper presents a method of calculating the time-dependent probability
      distribution of the microbial population size under arbitrary changes of
      temperature through time. To illustrate this method, the effect of a sudden
      temporary increase in temperature on the evolution of the probability
      distribution of Lactobacillus plantarum population size is presented. The effect
      of this change in temperature on the time taken for the population to reach a
      critical size, with a given probability, is also calculated and the application
      of this calculation to the design of HACCP protocols is discussed.

PMID- 11294354
TI  - High pressure increases bactericidal activity and spectrum of lactoferrin,
      lactoferricin and nisin.
AB  - We have studied the inactivation of a panel of eight test bacteria (two
      Escherichia coli strains, Salmonella enteritidis, Salmonella typhimurium,
      Shigella sonnei, Shigella flexneri, Pseudomonas fluorescens and Staphylococcus
      aureus) by high pressure in the presence of bovine lactoferrin (500 microg/ml),
      pepsin hydrolysate of lactoferrin (500 microg/ml), lactoferricin (20 microg/ml)
      and nisin (100 IU/ml). None of these compounds, at the indicated dosage, were
      bactericidal when applied at atmospheric pressure, except nisin, which caused a
      low level of inactivation of the bacteria. Under high pressure, lactoferrin,
      lactoferrin hydrolysate and lactoferricin displayed bactericidal activity against
      some of the test bacteria, however, the former had a narrower bactericidal
      spectrum than the two latter compounds. The bactericidal efficiency and spectrum
      of nisin were also enhanced under high pressure. The sensitisation of the test
      bacteria to these antimicrobials under pressure was transient, since no
      bactericidal activity was observed when bacteria were pressure treated before
      exposure to the compounds. We propose a mechanism of pressure-promoted uptake of
      these antimicrobial proteins and peptides in gram-negative bacteria to explain
      this sensitisation.

PMID- 11294355
TI  - A study on the effects of high pressure and heat on Bacillus subtilis spores at
      low pH.
AB  - Bacillus subtilis spore suspensions were subjected to pressure treatments at 100
      and 600 MPa at 40 degrees C and over a pH range from 3 to 8. Inactivation of
      spores under these conditions was maximally 80% and was not increased at low pH.
      However, higher levels of inactivation were obtained when spores were first
      pressure treated at neutral pH and then exposed for 1 h to low pH. This large
      difference in inactivation could be explained by the finding that pressure
      induced spore germination, which is known to occur at neutral pH, was inhibited
      at low pH (< 5). Pressure treatment at low pH made spores more sensitive to heat
      inactivation, suggesting that demineralized H-spores had been formed. Changes in
      spore core hydration and pH upon exposure of spores at low pH were studied in a
      more direct way using green fluorescent protein expressed in recombinant B.
      subtilis as a reporter protein, and it was confirmed that pressure and heat
      increase spore permeability for protons. Based on these results, the potential of
      low temperature, high pressure processes for spore inactivation in acid products
      is discussed.

PMID- 11294356
TI  - Microbial growth modelling with artificial neural networks.
AB  - There is a growing interest in modelling microbial growth as an alternative to
      time-consuming, traditional, microbiological enumeration techniques. Several
      statistical models have been reported to describe the growth of different
      microorganisms, but there are accuracy problems. An alternate technique
      'artificial neural networks' (ANN) for modelling microbial growth is explained
      and evaluated. Published data were used to build separate general regression
      neural network (GRNN) structures for modelling growth of Aeromonas hydrophila,
      Shigella flexneri, and Brochothrix thermosphacta. Both GRNN and published
      statistical model predictions were compared against the experimental data using
      six statistical indices. For training data sets, the GRNN predictions were far
      superior than the statistical model predictions, whereas the GRNN predictions
      were similar or slightly worse than statistical model predictions for test data
      sets for all the three data sets. GRNN predictions can be considered good,
      considering its performance for unseen data. Graphical plots, mean relative
      percentage residual, mean absolute relative residual, and root mean squared
      residual were identified as suitable indices for comparing competing models. ANN
      can now become a vehicle whereby predictive microbiology can be applied in food
      product development and food safety risk assessment.

PMID- 11294357
TI  - Lactobacillus alimentarius: a specific spoilage organism in marinated herring.
AB  - Spoilage characterised by bulging of lids and gas formation affected various
      product lots of different marinated herring types. Microbiological analyses
      resulted in growth on MRS and Rogosa SL agar. Altogether, 206 randomly selected
      colonies from two unspoiled and ten spoiled samples were characterised using
      phenotypical key tests and a 16 + 23S rRNA gene-based RFLP identification
      database. L. alimentarius was found to be the specific spoilage organism in all
      samples. All isolates obtained from the different product types were of the same
      clonal type. The slight rise in pH value together with marked gas production
      suggested a rare lactic acid bacteria spoilage type called 'protein swell'. L.
      alimentarius has not been previously associated with herring spoilage.

PMID- 11294358
TI  - An outbreak of food poisoning due to egg yolk reaction-negative Staphylococcus
      aureus.
AB  - An outbreak of staphylococcal food poisoning due to an egg yolk (EY) reaction
      negative strain occurred in Japan. Twenty-one of 53 dam construction workers who
      ate boxed lunches prepared at their company cafeteria became ill, and eight
      required hospital treatment. The outbreak showed a typical incubation time (1.5-4
      h with a median time of 2.7 h) and symptoms (vomiting and diarrhea) of
      staphylococcal food poisoning. Staphylococcus aureus, which produces
      staphylococcal enterotoxin (SE) A, was isolated from four fecal specimens of
      eight patients tested. Scrambled egg in the boxed lunches contained 20-40 ng/g of
      SEA, and 3.0 x 10(9)/g of viable S. aureus cells that produced this toxin. All
      isolates from patients and the food were EY reaction-negative, coagulase type II,
      and showed the same restriction fragment length polymorphism (RFLP) pattern. We
      concluded that the outbreak was caused by scrambled egg contaminated with EY
      reaction-negative S. aureus. In Japan, outbreaks of staphylococcal food poisoning
      are mainly caused by EY reaction-positive S. aureus, and EY reaction-negative
      colonies grown on agar plates containing EY are usually not analyzed further for
      detection of S. aureus. The present outbreak suggested that EY reaction-negative
      isolates should be subjected to further analysis to detect the causative agents
      of staphylococcal food poisoning.

PMID- 11294359
TI  - Biofilm formation by salmonella spp. on food contact surfaces and their
      sensitivity to sanitizers.
AB  - Biofilm formation by two poultry isolates of Salmonella on three commonly used
      food contact surfaces viz plastic, cement and stainless steel were studied.
      Biofilm formation of both the isolates showed a similar trend with the highest
      density being on plastic followed by cement and steel. Salmonella weltevreden
      formed biofilm with a cell density of 3.4 x 10(7), 1.57 x 10(6) and 3 x 10(5)
      cfu/cm2 on plastic, cement and steel respectively while Salmonella FCM 40 biofilm
      on plastic, cement and steel were of the order of 1.2 x 10(7), 4.96 x 10(6) and
      2.23 x 10(5) cfu/cm2 respectively. The sensitivity of the biofilm cells grown on
      these surfaces to different levels of two sanitizers namely hypochlorite and
      iodophor for varying exposure times was studied. Biofilm cells offered greater
      resistance when compared to their planktonic counterparts. Such biofilm cells in
      a food processing unit are not usually removed by the normal cleaning procedure
      and therefore could be a source of contamination of foods coming in contact with
      such surfaces.

PMID- 11294360
TI  - Influence of carvacrol on growth and toxin production by Bacillus cereus.
AB  - The natural antimicrobial compound carvacrol was investigated for its effect on
      diarrheal toxin production by Bacillus cereus. Carvacrol (0-0.06 mg/ml) reduced
      the viable count and the maximal specific growth rate (mumax) of B. cereus in BHI
      broth. The total amount of protein was not affected by carvacrol. However, a
      sharp decrease (80%) in diarrheal toxin production was observed in the presence
      of 0.06 mg/ml carvacrol. Carvacrol also inhibited toxin production in soup, but
      approximately 50-fold higher concentrations were needed to achieve the same
      effect as in broth. From this study it can be concluded that carvacrol can be
      added to food products at doses below the MIC value, thereby reducing the risk of
      toxin production by B. cereus and increasing the safety of the products.

PMID- 11294361
TI  - Influence of modified atmospheric storage, lactic acid, and NaCl on survival of
      sublethally heat-injured Listeria monocytogenes.
AB  - The effect of package atmosphere on survival of uninjured and sublethally heat
      injured Listeria monocytogenes, inoculated onto tryptose phosphate agar
      containing 0.85% lactic acid and 2% NaCl (TPALAS) was investigated. Inoculated
      TPALAS plates were packaged in air, 100% N2 (N2), 30% CO2-70% N2 (CO2-N2), and
      vacuum and stored at 4 and 20 degrees C for up to 31 days. Recovery of L.
      monocytogenes from TPALAS was influenced by the injury status (i.e., injured and
      uninjured) of the inoculum, storage atmosphere (air, N2, CO2-N2, and vacuum),
      storage temperature (4 and 20 degrees C), and recovery media [tryptose phosphate
      agar (TPA) and modified Oxford agar (MOX)] (P <0.05). Overall, storage at 4
      degrees C supported greater survival than storage at 20 degrees C (P< 0.05).
      Uninjured L. monocytogenes stored at 4 degrees C was recovered on TPA better than
      sublethally heat-injured L. monocytogenes stored at 40 degrees C (P < 0.05).
      Recovery of sublethally heat-injured L. monocytogenes stored at 4 degrees C
      followed the order N2 > CO2-N2 > air > vacuum (P < 0.05), whereas recovery of
      uninjured L. monocyrogenes stored at 4 degrees C followed the order N2 > CO2-N2 >
      vacuum > air (P < 0.05). Air and vacuum atmospheres supported greater survival of
      uninjured and heat-injured L. monocytogenes than N2 and CO2-N2 atmospheres at 20
      degrees C (P < 0.05). Recovery of sublethally heat-injured L. monocytogenes
      stored at 20 degrees C followed the order vacuum > air> CO2-N2 = N2 (P <0.05),
      whereas recovery of uninjured L. monocytogenes stored at 20 degrees C followed
      the order vacuum > air> CO2-N2 > N2 (P<0.05). Uninjured L. monocytogenes stored
      under N2 at 4 degrees C was recovered best, whereas sublethally heat-injured L.
      monocytogenes stored under N2 at 20 degrees C was recovered poorest (P < 0.05).
      Factors such as package atmosphere and storage temperature, involved in the
      production, storage, and distribution of fermented foods must be thoroughly
      evaluated when determining strategies for control and detection of L.
      monocytogenes in such products.

PMID- 11294362
TI  - Evaluation of motility enrichment on modified semi-solid Rappaport-Vassiladis
      medium (MSRV) for the detection of Salmonella in foods.
AB  - The detection and identification of Salmonella spp. is still troublesome and time
      consuming to the food industry. Employing the modified semi-solid Rappaport
      Vassiliadis medium (MSRV), presumptive results for Salmonella can be obtained in
      48 h, representing an interesting alternative to the standard methods. The
      specificity and sensitivity of the MSRV method were evaluated in this research.
      The efficiency of this method was also compared with the methodology recommended
      by the US Food and Drug Administration (FDA) using bismuth sulfite agar, XLT4
      agar and Rambach agar. A total of 146 food samples comprised of 41 chicken
      thighs, 35 Brazilian fresh pork sausages, 35 samples of cocoa powder and/or
      granulated cocoa and 35 samples of grated fresh coconut, were examined. Overall,
      the rapid method (direct + indirect) and the standard culture detected 96.1% and
      84.6% of the positive samples, respectively. No Salmonella was detected in the
      coconut or cocoa samples by any of the methods. Eighteen (43.9%) chicken thigh
      samples were contaminated with the microorganism. The rapid method (direct +
      indirect) and the standard culture detected 94.4% and 88.9% of these,
      respectively. Salmonella was detected in eight (22.8%) fresh pork sausage
      samples. The MSRV method detected Salmonella in all eight samples, while the
      standard gave positive results in six (75%). When compared with the standard
      method, the indirect method showed 86.4% sensitivity and 96.8% specificity, while
      the direct MSRV showed a sensitivity of 71.4% and specificity of 99.2%. Combined,
      both MSRV methods showed 95.5% sensitivity and 96.8% specificity. The MSRV medium
      also reduces the time necessary for the isolation of Salmonella from foods.

PMID- 11294363
TI  - Detection of Salmonella enteritidis in shell and liquid eggs using enrichment and
      plating.
AB  - Detection methods using various enrichment and plating media and
      immunoconcentration for Salmonella enteritidis in shell and liquid eggs were
      evaluated. For liquid egg samples naturally contaminated with S. enteritidis, pre
      enrichment in 225 ml of buffered peptone water with cysteine followed by
      selective enrichment in 10 ml of tetrathionate broth was the superior, resulting
      in the detection of S. enteritidis in all samples on six of the seven types of
      selective agar substrate investigated. This enrichment procedure also enabled
      detection of S. enteritidis in most of artificially inoculated shell egg and
      pasteurized liquid egg samples.

PMID- 11294364
TI  - Survival of Escherichia coli O157:H7 and Salmonella on chill-stored vacuum or
      carbon dioxide packaged primal beef cuts.
AB  - The ability of two Escherichia coli O157:H7 strains (E27, a cattle isolate, and
      B6-914 gfp-91, a fluorescent marker strain) and two Salmonella serotypes (S.
      typhimurium and S. brandenberg) to survive on chilled preservatively packaged
      primal beef cuts was examined. Each of the strains was inoculated separately at
      two dilution levels (10(3) and 10(5) cfu g(-1)) onto 500 g beef steaks, packaged
      under vacuum or 100% carbon dioxide, and stored, with uninoculated controls, for
      6 weeks at - 1.5 degrees C, then for 2 weeks at 4 degrees C. Bacterial numbers
      were determined by dilution and incubation at 37 degrees C for 24 h on either
      Sorbitol McConkey Agar or Xylose Lysine Desoxycholate Agar for E. coli O157:H7
      and Salmonella samples, respectively. Counts were corrected for background growth
      and their accuracy checked using immunological tests. Fluorescent E. coli O157:H7
      B6-914 gfp-91 was also counted under ultra-violet light. No significant changes
      in numbers of the E. coli O157:H7 or Salmonella strains occurred during storage
      at either - 1.5 or 4 degrees C packaged under either vacuum or carbon dioxide.
      The ability of these pathogens to survive standard preservative packaging
      conditions is different from that reported from their generic counterparts and
      therefore a cause for public health concern.

PMID- 11294365
TI  - Bibliography of food microbiology.

PMID- 11294366
TI  - Pharmacokinetics and pharmacodynamics of temocapril during repeated dosing in
      elderly hypertensive patients.
AB  - OBJECTIVE: To evaluate the pharmacokinetic profiles of temocaprilat and its
      hypotensive effect after single and repeated dosings of temocapril in young and
      elderly hypertensive patients. METHODS: An angiotensin-converting enzyme
      inhibitor, temocapril (2 mg), was given once daily for 8 days to nine young and
      ten elderly hypertensive patients. Pharmacokinetics of temocaprilat, an active
      metabolite, and its hypotensive effect were evaluated after the first and last
      doses. RESULTS: The area under the plasma concentration-time curve (AUC) of
      temocaprilat after the first dose was significantly greater in the elderly than
      in the young. This parameter was elevated after the final dose in both groups.
      The AUC (eighth dose)/AUC (first dose) ratio in the elderly was similar to that
      in the young. Blood pressure (BP) tended to decrease in the young and
      significantly decreased in the elderly after the first dose. The hypotensive
      effect was not enhanced after the final dose in either group. CONCLUSION: These
      results suggest that although plasma temocaprilat concentration rises during
      repeated dosing, its BP-lowering effect is not enhanced in the elderly.
      Therefore, if a remarkable BP reduction is not detected at the initiation of
      treatment, the risk of hypotensive episode might be small during long-term
      therapy with temocapril in elderly hypertensive patients.

PMID- 11294367
TI  - Salmeterol and fluticasone propionate given as a combination. Lack of systemic
      pharmacodynamic and pharmacokinetic interactions.
AB  - OBJECTIVE: To investigate the potential for systemic pharmacodynamic and
      pharmacokinetic interactions between inhaled salmeterol and fluticasone
      propionate when repeat doses of the two drugs are given in combination to healthy
      subjects. METHODS: Twenty-eight healthy subjects received salmeterol 100 microg,
      salmeterol 100 microg/fluticasone propionate 500 microg and fluticasone
      propionate 500 microg via a Diskus dry powder inhaler twice daily for 11 days
      according to a randomised, double-blind, placebo-controlled, crossover design.
      Subjects in the placebo group also received a single dose of salmeterol 100
      microg on the morning of day 10. On day 10, the systemic effects of salmeterol
      [on pulse rate, blood pressure, corrected QT (QTc) interval and serum potassium
      and glucose levels] and fluticasone propionate (on 24-h urinary cortisol and
      morning plasma cortisol levels) were assessed. Maximal number and affinity of
      lymphocyte beta2-adrenoceptors and beta2-adrenoceptor polymorphism at loci 16 and
      27 were also determined. Plasma pharmacokinetics of salmeterol and fluticasone
      propionate were determined after the morning dose on day 10. Dosing continued on
      the evening of day 10 and on day 11, and on day 12 the effect of repeat-dose
      treatment with salmeterol and salmeterol/fluticasone propionate on the systemic
      effects of cumulative doses of inhaled salbutamol (up to a total dosage of 3,200
      microg) was evaluated. RESULTS: All treatments were safe and well tolerated. With
      the exception of a higher pulse rate after repeat administration of salmeterol
      [66.2 beats per minute (bpm) versus 63.6 bpm], there were no significant
      differences between the single-dose and repeat-dose salmeterol groups. The
      systemic pharmacodynamic effects of inhaled salmeterol were not affected by the
      co-administration of fluticasone propionate. Eleven days of treatment with
      salmeterol induced tachyphylaxis to the systemic effects of cumulative doses of
      salbutamol; however, co-administration of fluticasone propionate did not affect
      the response to salbutamol. Fluticasone propionate reduced 24-h urinary cortisol
      excretion (22.4 microg compared with 48.6 microg with placebo), but this was
      unaffected by the co-administration of salmeterol. Morning plasma cortisol levels
      were not reduced compared with placebo. There was no significant treatment effect
      on lymphocyte beta2-adrenoceptors and no correlation of beta2-adrenoceptor
      polymorphism at loci 16 and 27 with the development of tachyphylaxis. Salmeterol
      plasma concentrations were measurable only during the first half-hour after
      dosing. Co-administration of fluticasone propionate did not affect the peak
      plasma concentration (Cmax) of salmeterol. For fluticasone propionate, there were
      no statistically significant differences between salmeterol/fluticasone
      propionate and fluticasone propionate with respect to Cmax, plasma concentration
      at the end of the dosing interval (Ct), terminal elimination half-life (t1/2) or
      time to Cmax (tmax). The area under the concentration-time curve within a dosing
      interval (AUCt) for fluticasone propionate after inhalation of
      salmeterol/fluticasone propionate was statistically significantly higher (about
      8%) than after inhalation of fluticasone propionate alone (P=0.0135). However,
      the 90% confidence intervals (CIs) for the AUCt and Cmax ratios for the two
      treatments were within the accepted limits for bioequivalence (1.03, 1.13 and
      0.97, 1.12, respectively). CONCLUSION: These results in healthy subjects indicate
      that there is no systemic pharmacodynamic or pharmacokinetic interaction between
      inhaled salmeterol and fluticasone propionate when given in combination.

PMID- 11294368
TI  - Is diclofenac a valuable CYP2C9 probe in humans?
AB  - INTRODUCTION: Besides the low therapeutic index drug tolbutamide, there is no
      validated in vivo probe to assess the genetically determined CYP2C9 activity in
      humans. The in vitro CYP2C9-specific substrate diclofenac might be a valuable,
      well-tolerated probe candidate. In order to validate diclofenac as an in vivo
      CYP2C9 probe, we planned to show that urinary 4'-hydroxydiclofenac/diclofenac
      metabolic ratio (MR) would correlate to the apparent partial metabolic clearance
      of diclofenac into 4'-hydroxydiclofenac (Clmet). PATIENTS AND METHODS: Eighteen
      healthy volunteers received a single oral dose of 50 mg diclofenac in its enteric
      coated form. Blood and urinary pharmacokinetics of diclofenac were studied over
      48 h. Identification of the CYP2C9 alleles (CYP2C9*1, CYP2C9*2, and CYP2C9*3) was
      performed with genomic DNA sequencing. RESULTS: We observed a dramatic inter
      individual variability in the delay of diclofenac intestinal absorption since its
      first detectable blood concentration ranged from 0.5 h to more than 12 h after
      drug intake. The Clmet of diclofenac could not be determined in two subjects who
      started to absorb the drug after 12 h. No correlation could be observed between
      Clmet of diclofenac and the different MRs calculated at 0-4 h, 0-8 h, 0-12 h, 0
      24 h and 0-48 h urinary collections. The Clmet of diclofenac in heterozygous
      subjects tended to be lower than among wild-type homozygous subjects, but this
      difference did not reach statistical significance due to an insufficient number
      of subjects studied. CONCLUSION: Diclofenac, in its enteric-coated form, is not a
      useful in vivo CYP2C9 probe probably because of its highly variable intestinal
      absorption rate. However, since we found a lower metabolic clearance of
      diclofenac in heterozygous CYP2C9 subjects, as observed with other CYP2C9
      substrates, diclofenac, in another galenic form, might be a potential probe to
      quantify CYP2C9 activity in humans.

PMID- 11294369
TI  - The effects of grapefruit juice on the pharmacokinetics of erythromycin.
AB  - OBJECTIVE: To study the effects of grapefruit juice on the pharmacokinetics of
      erythromycin. METHODS: The effects of grapefruit juice intake on the
      pharmacokinetics of erythromycin were investigated in six healthy male
      volunteers, who received 400 mg erythromycin with either water or grapefruit
      juice. The measurement of erythromycin in plasma samples were achieved by simple
      Sep-Pak CN cartridge extraction coupled with the electrochemical determination
      HPLC method, which was developed for the determination of erythromycin in human
      plasma in the present study. RESULTS: Grapefruit juice, compared with water
      intake, significantly (P<0.05) increased the mean Cmax value (1.65+/-0.94 versus
      2.51+/-0.68 microg/ml) and the mean AUC0-12 value of erythromycin (5.92+/-3.25
      versus 8.80+/-1.32microg.h/ml). However, the Tmax and t1/2 values of erythromycin
      were not affected by grapefruit juice intake. CONCLUSION: These results indicate
      that the bioavailability of erythromycin was increased by the inhibitory effect
      of grapefruit juice on cytochrome P450 (CYP) 3A4-mediated metabolism in the small
      intestine.

PMID- 11294370
TI  - Pharmacokinetics and safety of escalating single and repeat oral doses of
      GW420867X, a novel non-nucleoside reverse transcriptase inhibitor.
AB  - OBJECTIVE: To assess the pharmacokinetics, safety and tolerability of escalating
      oral doses of GW420867X, a non-nucleoside reverse transcriptase inhibitor, was
      investigated in healthy male volunteers in a randomized, double-blind placebo
      controlled study. METHODS: Study subjects were divided into four groups of 12
      subjects (10, 50, 100 and 200-mg dose groups) with eight subjects from each group
      receiving active treatment and the remaining four matched placebo. Subjects were
      initially administered a single dose of GW420867X or placebo, and following a 24-
      to 28-day washout period, re-exposed to the same treatment for 14 consecutive
      days. Safety measurements including clinical laboratory evaluations, ECG and
      vital signs were performed before, during and after dosing. RESULTS: Geometric
      mean GW420867X peak plasma concentrations (Cmax) following single oral doses of
      10, 50, 100 and 200 mg were 160, 608, 1,000 and 1,662 ng/ml, respectively. Time
      to Cmax (tmax) increased from a median value of 1 h following the 10-mg dose, to
      3 h after the 200-mg dose. Geometric mean plasma areas under the curves (AUC)
      were 4,325 (10 mg), 17,862 (50 mg), 35,295 (100 mg) and 62,338 ng/ml per hour
      (200 mg) and were proportionally less than the increase in the administered dose.
      Apparent terminal elimination half-life (t1/2) was approximately 50 h. Following
      repeat dosing, accumulation ratios based on plasma AUC were: 3.0+/-1.0 (10mg),
      2.6+/-0.9 (50mg), 1.8+/-0.3 (100 mg) and 1.9+/-0.8 (200 mg) after 14 days of
      dosing compared to the corresponding single dose. In general, oral clearance
      (CL/F) was greater after 14 days and greater with higher doses except for the 10
      mg dose group. Steady-state CL/F was 2.2, 3.4, 4.2, and 5.1 l/h for 10, 50, 100,
      and 200 mg, respectively. Steady-state was generally achieved within 7-10 days.
      Comparison of single and repeat dosing with GW420867X showed that Cmax increased
      by a factor of between 1.4 to 1.8, after 14 days of daily dosing to 288 (10 mg),
      1,006 (50 mg), 1,401 (100 mg) and 2,613 (200 mg) ng/ml. These increases were
      proportionally less than the increase in the administered dose. GW420867X was
      well tolerated by subjects both after single and repeated dosing. Adverse effects
      reported by subjects on the active drug were similar to those receiving placebo.
      All episodes were rated as mild to moderate in severity and resolved
      spontaneously without further intervention. CONCLUSION: The pharmacokinetic
      findings of this study imply that systemic exposure to GW420867X decreases with
      increasing dose and displays time-variant pharmacokinetics, which suggests
      decreased absorption and/or increased clearance of GW420867X. The relatively long
      plasma half-life, of approximately 50 h, makes it suitable for once-daily dosing.

PMID- 11294371
TI  - Pharmacokinetic investigation of a nicotine sublingual tablet.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of a new 2-mg nicotine sublingual
      tablet under varying conditions of use. METHODS: The pharmacokinetics of the 2-mg
      nicotine sublingual tablet were investigated in four separate studies involving
      healthy adult volunteer smokers: (1) a multiple-dose comparison with 2-mg
      nicotine chewing gum (n=24; 13 males, 11 females), (2) a dose-proportionality
      study comparing single doses of 2, 4 and 6 mg (n=21, 10 males, 11 females), (3)
      an evaluation of the effect of incorrect tablet use, i.e. chewing the tablet
      followed by either immediate or delayed swallowing (n = 19, 10 males, 9 females),
      and (4) the effect of oral and gastric pH on nicotine absorption from the tablet
      (n=20; 11 males, 9 females). Study parameters were maximal plasma concentration
      (Cmax), time to Cmax (tmax), and area under the plasma concentration-time curve
      (AUC). RESULTS: The plasma nicotine profiles were similar following repeated
      administration of the sublingual tablet and the 2-mg nicotine chewing gum (mean
      Cmax 13.2 versus 14.4 ng/ml, median tmax 20 versus 20 min, mean AUC11-12 12.4
      versus 13.5 ng/ml per hour) with no statistically significant difference between
      the two treatments. The pharmacokinetics of the 4- and 6-mg doses were non-linear
      compared to the 2-mg dose, probably as a result of more of the dose being
      swallowed and undergoing first-pass metabolism in the liver. The mean Cmax for
      the 2-, 4- and 6-mg dose was 3.8 +/- 1.0, 6.8 +/- 2. 1, and 9.0 +/- 3.3 ng/ml,
      respectively, and in terms of dose proportionality the relative bioavailability
      of the 4- and 6-mg dose was 0.82 and 0.71, respectively. Incorrect tablet use,
      i.e. chewing the tablet and immediate swallowing decreased nicotine
      bioavailability both in terms of rate and extent. Mean Cmax was 12.1 ng/ml
      (correct use), 10.3 ng/ml (chewing and immediate swallowing), and 12.1 ng/ml
      (chewing and delayed swallowing). Corresponding mean values for AUC9-10 were
      11.6, 9.6 and 11.2 ng/ml per hour. There were no significant differences between
      'alkaline mouth' versus control, 'acidic mouth' versus control or 'alkaline
      stomach' versus control, but the rate of nicotine absorption was increased at
      alkaline compared to acidic oral pH (mean Cmax 6.1 versus 4.9 ng/l ml, P = 0.003;
      median tmax 60 versus 90 min, P= 0.0002). CONCLUSION: The pharmacokinetic profile
      of the nicotine 2-mg tablet was similar to that of the 2-mg nicotine chewing gum.
      Absorption of nicotine from the tablet was nonlinear at higher doses (two or
      three tablets). Chewing the tablet and keeping the remains in the mouth or
      concurrent use of acidic beverages or antacids are equivalent to recommended
      sublingual use during normal oral pH conditions.

PMID- 11294372
TI  - Pharmacokinetics of entacapone, a peripherally acting catechol-O
      methyltransferase inhibitor, in man. A study using a stable isotope techique.
AB  - OBJECTIVE: This study investigated the pharmacokinetics of the catechol-O
      methyltransferase (COMT) inhibitor entacapone by giving simultaneously stable non
      radioactive isotope 13C-entacapone intravenously (i.v.) and unlabelled entacapone
      orally. In comparison with a crossover design, the simultaneous i.v. and oral
      administration made it possible to minimise intra-individual variation, sample
      size and the duration of the study and still obtain accurate pharmacokinetic
      data. METHODS: Eight healthy male volunteers were enrolled in this study. They
      were given a 20-mg i.v. dose of 13C-entacapone as a 1-mg/ml infusion at a
      constant rate of 5 mg/min over 4 min and a 100-mg dose of unlabelled entacapone
      orally immediately after the infusion. Blood samples were drawn at -5 (before
      onset of infusion), 0 (upon termination of infusion), 2, 5, 10, 20, 30 and 45 min
      and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 12 h after the tablet ingestion. Urine
      during the 48 h after dosing was collected in fractions. Concentrations of 13C
      entacapone and entacapone in plasma samples and urine fractions were determined
      using gas chromatography-mass spectrometry. RESULTS: The decay of i.v. 13C
      entacapone in plasma was tri-exponential and its pharmacokinetics were described
      using an open three-compartment model. The volume of the central compartment (Vc)
      and the volume of distribution at steady state (Vss) were 0.08+/-0.03 l/kg and
      0.27+/-0.10 l/kg, respectively. Total plasma clearance (Cltot) averaged 11.7+/
      1.9 ml/min kg(-1). The half-lives for the distribution phase and for the rapid
      and terminal elimination phases (t1/2alpha, t1/2beta and t1/2gamma) were 0.05+/
      0.01 h, 0.38+/-0.16 h and 2.40+/-1.70 h, respectively. The terminal elimination
      phase accounted for only 9% of the total area under the plasma concentration-time
      curve (AUC), which was 409 +/- 98 ng h/ml after the i.v. dose. Oral entacapone
      was absorbed rapidly with a time to reach the peak concentration (tmax) of 0.9+/
      0.4 h, a maximum concentration (Cmax) of 457+/-334 ng/ml and an AUC of 497+/-118
      ng h/ml. During the 48 h after dosing, the recovery of free and conjugated
      unchanged 13C-entacapone in urine was 38.1+/-7.2% of the i.v. dose and the
      recovery of free and conjugated unchanged entacapone 13.3+/-3.9% of the oral
      dose. The bioavailability of oral entacapone was 25% based on the AUC values and
      35% based on urinary excretion. CONCLUSION: The results of the present study
      using stable isotope technique indicate that entacapone is rapidly absorbed,
      distributed to a small volume and rapidly eliminated by mainly non-renal routes.
      The pharmacokinetic profile of entacapone provides the rationale for a
      concomitant and frequently repeated simultaneous dosing of entacapone with
      levodopa and dopa decarboxylase inhibitors in the treatment of Parkinson's
      disease. This study confirmed the previously published data and fully support the
      validity of the technique used.

PMID- 11294373
TI  - In vivo measurement of [11C]verapamil kinetics in human tissues.
AB  - OBJECTIVE: To evaluate [11C]verapamil kinetics in humans. METHODS: After
      intravenous injection of [11C]verapamil (370 MBq, specific activity >1,600
      GBq/mmol), kinetics were evaluated in five cancer patients using positron
      emission tomography (PET). RESULTS: One hour after injection, accumulation of
      [11C] in lungs, heart and tumour was 43.0%, 1.3% and 0.9% of the injected
      verapamil dose, respectively. Half-lives of [11C]verapamil in these tissues were
      46.2 min, 73.8 min and 23.7 min, respectively. CONCLUSIONS: Intravenously
      administered [11C] was mainly extracted by the lungs. Transport of a
      [11C]verapamil bolus out of solid tumour tissue is relatively fast.

PMID- 11294374
TI  - Pilot study of prescription-event monitoring in Japan comparing troglitazone with
      alternative oral hypoglycemics.
AB  - OBJECTIVE: To examine adverse events reported in a pilot study of the
      prescription-event monitoring in Japan (J-PEM) scheme, comparing troglitazone
      with other oral hypoglycemics. METHODS: We used a cohort study with a concurrent
      control in which information was gathered from both doctors and pharmacists.
      Crude event rates were calculated and compared between troglitazone (T) and
      alternative oral hypoglycemics (control drugs, C) using the likelihood ratio
      test. When the difference was statistically significant, possible confounding
      mechanisms were examined using Poisson regression analysis. RESULTS: Of 3,115
      patient codes registered, pharmacists were sent 2,078 questionnaires and returned
      1,814 (87%), while doctors were sent 1,858 questionnaires and returned 671 (36%).
      The difference in crude rates was statistically significant in 11 events (seven
      where T > C and four where C > T) reported by pharmacists and ten events (three
      where T > C and seven where C > T) reported by doctors. Among those, in two
      events, "weight increased" (T > C) and "abnormal hepatic function" (T > C),
      significant differences were observed in data from both doctors and pharmacists.
      Regression analysis revealed that the difference in crude rates for "nausea" (T >
      C) was possibly due to an uneven distribution of genders and that for "weight
      increased" (T >C) was possibly due to an uneven distribution of compliance.
      Patients with hepatic function abnormalities associated with troglitazone could
      be divided into two subtypes: one with a slight increase in serum lactate
      dehydrogenase concentration only and the other with elevated serum alanine
      aminotransferase. CONCLUSIONS: Comparison of the event rates between troglitazone
      and control drugs, followed by regression analysis, revealed several features of
      adverse events associated with drugs, including possible confounding mechanisms.
      Troglitazone-induced hepatic function abnormalities may be divided into two
      subtypes.

PMID- 11294375
TI  - Off-label and unlicensed use of antidotes in paediatric patients.
AB  - OBJECTIVE: To determine the extent of unlicensed and off-label antidotes among
      medicines recommended by the International Programme on Chemical Safety (IPCS)
      for children. MATERIALS AND METHODS: We considered 77 antidotes from the "IPCS
      List of antidotes and other useful agents in the treatment of human poisoning"
      (1996 version). Primary reference sources used were the Physicians' Desk
      Reference (PDR) and package inserts. Antidotes were assessed for off-label
      (outside of the term of product license) and unlicensed use in children. RESULTS:
      Our data show that only 31 (40.3%) of 77 recommended antidotes correspond to the
      demands of licensing systems for use in children. The rest (46 or 59.7%) are
      either off-label (32 or 41.5%) or unlicensed (14 or 18.2%). Five antidotes are
      off-label for two reasons; thus the total number of off-label use (37) is greater
      than the number of such drugs (32). Inappropriate age is the main reason for use
      outside the stipulations of the product license (24 of 77 antidotes or 31.2%),
      whereas different indication and route occur in 11 (14.3%) and 2 (2.6%)
      antidotes, respectively. The 14 unlicensed antidotes have been used only in
      animal experiments or in a small number of patients in certain poison centres.
      CONCLUSIONS: Sixty percent of antidotes and other useful agents in the poison
      treatment of children do not correspond to the demands of licensing systems.
      Drugs used in the treatment of poisoned children, as well as adults, must be
      evaluated scientifically.

PMID- 11294376
TI  - Feedback on prescribing rate combined with problem-oriented pharmacotherapy
      education as a model to improve prescribing behaviour among general
      practitioners.
AB  - OBJECTIVE: To develop a working model with which prescribing behaviour among
      general practitioners might be influenced. DESIGN: Intervention based on feedback
      on prescribing rates and problem-oriented educational outreach visits, using
      educational material and local opinion leaders. Randomised study with three
      parallel intervention groups of general practitioners, which also served as
      controls for each other. The pharmacotherapeutic fields chosen were hypertension,
      peptic ulcer/dyspepsia and depression. Prescription data were retrieved from the
      electronic patient records for periods of 1 year before and after the
      intervention. SETTING: Six health care centres and three continuing medical
      education groups in Stockholm. SUBJECTS: Forty general practitioners. MAIN
      OUTCOME MEASURES: Drug prescribing rates and patterns before and after the
      intervention. RESULTS: In the hypertension field, desired trends in fractional
      prescribing (favouring diuretics and beta blocking agents) were recorded, with a
      significant (P < 0.05) effect on prescriptions for agents acting on the renin
      angiotensin system, despite a pre-existing prescribing behaviour already much in
      line with the goals. In the peptic ulcer/dyspepsia field, desired trends were
      recorded for both types of therapies addressed. The fractional prescribing rates
      for proton-pump inhibitors decreased from 61.0% to 52.6% in the intervention arm
      and increased from 68.1% to 76.0% in the control arm (not significant due to low
      power). The depression group focused on better general attention to the disease
      and only minor changes were registered. CONCLUSION: Feedback of individual
      prescribing rates, combined with problem-oriented educational outreach visits, is
      a promising model for the improvement of prescribing behaviour. Data from the
      electronic patient record were feasible for feedback on prescribing rates.

PMID- 11294377
TI  - Genetic polymorphism of CYP2D6 in Tamil population.

PMID- 11294378
TI  - Clinical research: the influence of the pharmaceutical industry.
AB  - OBJECTIVE: The aim of the investigation is to throw light on the influence of the
      pharmaceutical industry on clinical research in Norway. The files of the five
      regional medical research ethics committees, which contain the application forms
      and the protocols of all the research projects on humans, were used as source for
      the statistics. The projects were first classified and registered in two groups:
      pharmacology/pharmacotherapy and others. Then the pharmacology/pharmacotherapy
      group was divided into projects sponsored or initiated by the industry and
      others. RESULTS: In the 3 years 1988-1990, the yearly average number of projects
      was 360. Sixty-two percent of the projects were pharmacology/pharmacotherapy;
      seventy-nine percent of these projects were conducted by the industry. The
      corresponding figures for the year 1997 were 747, 40% and 68%, respectively. We
      have not been able to find similar statistics from other countries. CONCLUSION:
      Our conclusion is that research in pharmacology/pharmacotherapy should be more
      independent of industry.

PMID- 11294379
TI  - 2-Arylindole-3-acetamides: FPP-competitive inhibitors of farnesyl protein
      transferase.
AB  - A series of 2-arylindole-3-acetamide farnesyl protein transferase inhibitors has
      been identified. The compounds inhibit the enzyme in a farnesyl pyrophosphate
      competitive manner and are selective for farnesyl protein transferase over the
      related enzyme geranylgeranyltransferase-I. A representative member of this
      series of inhibitors demonstrates equal effectiveness against HDJ-2 and K-Ras
      farnesylation in a cell-based assay when geranylgeranylation is suppressed.

PMID- 11294381
TI  - Sodium etiobilirubin-IVgamma-C10-sulfonate: a highly solvated bile pigment
      structure containing two different non-ridge-tile conformers in the unit cell.
AB  - The crystal structure of the title compound is the first example of a bilirubin
      existing in both extended and cyclic conformations and the first bile pigment
      structure showing two markedly different conformations in the unit cell. In
      contrast to previous rubin structures the dipyrrinone rings are twisted out of
      planarity in both conformers. Because of numerous hydrogen-bonding and ionic
      interactions a highly complex tetrameric structure is observed in which each
      extended conformer is held pincer-like by another.

PMID- 11294380
TI  - Novel sulfonate analogues of combretastatin A-4: potent antimitotic agents.
AB  - Sulfonate analogues of combretastatin A-4 have been prepared. These compounds
      compete with colchicine and combretastatin A-4 for the colchicine binding site on
      tubulin and are potent inhibitors of tubulin polymerization and cell
      proliferation. Importantly, these compounds also inhibit the proliferation of P
      glycoprotein positive (+) cancer cells, which are resistant to many other
      antitumor agents.

PMID- 11294382
TI  - Synthesis and structure-activity relationships of 1-phenylpyrazoles as xanthine
      oxidase inhibitors.
AB  - A series of 1-phenylpyrazoles was evaluated for inhibitory activity against
      xanthine oxidase in vitro. Of the compounds prepared, 1-(3-cyano-4
      neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700) had the most potent enzyme
      inhibition and displayed longer-lasting hypouricemic action than did allopurinol
      in a rat model of hyperuricemia induced by the uricase inhibitor potassium
      oxonate.

PMID- 11294384
TI  - Synthesis of tetrocarcin derivatives with specific inhibitory activity towards
      Bcl-2 functions.
AB  - Tetrocarcin A was recently identified as an inhibitor of the anti-apoptotic
      function of Bcl-2. We synthesized novel tetrocarcin derivatives in order to
      increase their selective inhibitory activity against Bcl-2. It was found that 21
      acetoxy-9-glycosyloxy derivatives had potent Bcl-2 inhibitory activity without
      significant antimicrobial activity.

PMID- 11294383
TI  - Cis- and trans-N-benzyl-octahydrobenzo[g]quinolines. Adrenergic and dopaminergic
      activity studies.
AB  - In vitro assays on a series of cis- and trans-octahydrobenzo[g]quinolines
      indicated an unusual trend of affinities at the dopaminergic receptors and alpha
      adrenoceptors. The trans N-benzyl analogues exhibited affinity at the alpha2 as
      well as the D1-like receptors whereas their N-unsubstituted congeners showed a
      distinct preference for the alpha2 adrenoceptor. Enhanced activity for the alpha2
      receptors was also exhibited by the cis N-benzylated isomers. These observations
      are interpreted by theoretical calculations.

PMID- 11294385
TI  - Design and synthesis of ether analogues as potent and selective M2 muscarinic
      receptor antagonists.
AB  - Novel, selective M2 muscarinic antagonists, which replace the metabolically
      labile styrenyl moiety of the prototypical M2 antagonist 1 with an ether linkage,
      were synthesized. A detailed SAR study in this class of compounds has yielded
      highly active compounds that showed M2 Ki values of < 1.0 nM and >100-fold
      selectivity against M1, M3, and M5 receptors.

PMID- 11294386
TI  - The discovery of a potent, intracellular, orally bioavailable, long duration
      inhibitor of human neutrophil elastase--GW311616A a development candidate.
AB  - The discovery of a potent intracellular inhibitor of human neutrophil elastase
      which is orally active and has a long duration of action is described. The
      pharmacodynamic and pharmacokinetic properties of a trans-lactam development
      candidate, GW311616A, are described.

PMID- 11294387
TI  - Acid dissociation constant, a potential physicochemical factor in the inhibition
      of the enzyme estrone sulfatase (ES).
AB  - We report the initial results of the synthesis and biochemical evaluation of a
      series of aminosulfonate based compounds of phenol and the determination of the
      pKa of the parent phenol in an attempt to investigate the role of this
      physicochemical factor in the irreversible inhibition of the enzyme estrone
      sulfatase (ES). The results of the study show that there is a strong correlation
      between the observed pKa and inhibitory activity. We postulate that the stability
      of the phenoxide ion, as indicated by the acid dissociation constant, is an
      important factor in the irreversible inhibition of this enzyme.

PMID- 11294388
TI  - Syntheses and antifungal activities of novel 3-amido bearing pseudomycin
      analogues.
AB  - As a result of our core SAR effort, we discovered a large number of 3-amido
      pseudomycin B (PSB) analogues (e.g., 4e LY448212 and 5b LY448731) that retain
      good in vitro and in vivo (IP) activities against Candida and Cryptococcus
      without inherent tail vein irritation. Several dimethylamino termini bearing 3
      amides (e.g., 5b) also exhibited improved potency against Aspergillus in vitro.
      When evaluated in a two-week rat toxicology study, it was found that all animals
      receiving 4e (up to 75 mg/kg) were found to be normal. On the basis of these
      observations, we are convinced that it is possible to broaden the antifungal
      spectrum and improve the safety profile of pseudomycin analogues at the same
      time.

PMID- 11294389
TI  - LY294002-geldanamycin heterodimers as selective inhibitors of the PI3K and PI3K
      related family.
AB  - Several LY294002-GM heterodimers were synthesized with the intent of modulating
      their activity in the presence of hsp90 and thereby creating selective inhibitors
      of PI3K and PI3K-related family.

PMID- 11294390
TI  - Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their
      biological evaluation as urokinase inhibitors.
AB  - The serine protease urokinase (uPa) has been implicated in the progression of
      both breast and prostate cancer. Utilizing structure based design, the synthesis
      of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-carboxamidines
      is described. Further optimization of this series by substitution of the terminal
      amine yielded urokinase inhibitors with excellent activities.

PMID- 11294392
TI  - Synthesis and biological evaluation of a sialyl Lewis X mimic with significantly
      improved E-selectin inhibition.
AB  - The synthesis of the highly potent E-selectin inhibitor 5 is described. Sialyl
      Lewis X mimic 5 was rationally designed by combining two previously disclosed
      beneficial sLe(x) modifications in a single molecule. The compound was found to
      be 30-fold more potent than sLe(x) in a static, cell-free equilibrium assay.
      Furthermore, compound 5 was highly active (IC50 = 10 microM) in a dynamic non
      equilibrium assay in which sLe(x) did not inhibit neutrophil rolling at up to
      1000 microM.

PMID- 11294391
TI  - Synthesis and biological evaluation of benzo[b]naphthyridones, a series of new
      topical antibacterial agents.
AB  - We describe here the synthesis and biological evaluation of a series of
      benzo[b]naphthyridones, a new family of tricyclic antibacterial compounds that
      have a gram-positive spectrum of activity. RP60556A, one of the most potent of
      these compounds, is bactericidal against multiresistant cocci, especially
      multiresistant Staphylococcus aureus strains. Its physico-chemical and biological
      properties make it particularly suitable for topical antibacterial use.

PMID- 11294393
TI  - Water-soluble propofol analogues with intravenous anaesthetic activity.
AB  - Propofol (2,6-diisopropylphenol) is a widely used intravenous anaesthetic that is
      formulated as an emulsion since it lacks water solubility. We report a range of
      water-soluble analogues of propofol, containing a para-alkylamino substituent,
      which retain good intravenous anaesthetic activity in rodents.

PMID- 11294394
TI  - Use of an aminooxy linker for the functionalization of oligodeoxyribonucleotides.
AB  - We describe the preparation of oligonucleotides containing a 5'-linker bearing an
      aminooxy group. Use of the trityl protecting group for the aminooxy moiety allows
      purification of the modified oligonucleotide by reverse phase HPLC and cleavage
      in mild acidic conditions. Derivatization with an aldehydic reporter group is
      efficient and rapid.

PMID- 11294395
TI  - The adenine derivative of alpha-L-LNA (alpha-L-ribo configured locked nucleic
      acid): synthesis and high-affinity hybridization towards DNA, RNA, LNA and alpha
      L-LNA complementary sequences.
AB  - Synthesis of a 9-mer alpha-L-LNA (alpha-L-ribo configured locked nucleic acid)
      containing three 9-(2-O,4-C-methylene-alpha-L-ribofuranosyl)adenine nucleotide
      monomer(s) has been accomplished. The work involved synthesis of the bicyclic
      adenine nucleoside via a condensation reaction between L-threo-pentofuranose
      derivative 1 and 6-N-benzoyladenine followed by C2'-epimerization. Hybridization
      studies demonstrated very strong duplex formation with 9-mer complementary DNA,
      RNA, LNA and alpha-L-LNA target sequences.

PMID- 11294397
TI  - Bile acid-oligodeoxynucleotide conjugates: synthesis and liver excretion in rats.
AB  - The synthesis of bile acid oligodeoxynucleotide conjugates via the 3-OH group of
      the bile acids is described. When used in vivo in rats, covalent conjugation of
      an oligodeoxynucleotide via a linker to cholic acid resulted in an increased
      biliary excretion of bile acid-oligodeoxynucleotide conjugates compared to
      unconjugated oligodeoxynucleotides.

PMID- 11294396
TI  - Selective delta-opioid receptor ligands: potential PET ligands based on
      naltrindole.
AB  - Two series of delta-selective ligands related to the prototypic delta-antagonist
      naltrindole have been prepared and evaluated in opioid binding assays with the
      aim of developing new PET ligands for the delta-opioid receptor. One compound
      (5d) had significantly higher selectivity than naltrindole, but with
      substantially reduced binding affinity. For those compounds retaining similar
      affinity to naltrindole, those having ethyl and fluoroethyl substituents afforded
      the highest levels of selectivity. However, none of the compounds combined the
      high level of affinity and selectivity ideally suited to the development of an
      imaging agent.

PMID- 11294398
TI  - Different antagonist binding properties of human and rat histamine H3 receptors.
AB  - Different histamine H3-receptor antagonists have been tested in displacement
      studies at human and rat H3 receptors in stably transfected cells. Based on an
      actual rhodopsin structure, models for receptor antagonist interaction were
      developed for receptors of both species. Similarities and discrepancies in
      binding profiles can be explained, but not quantified by hydrophilic interactions
      with Asp114 and an important lipophilic binding pocket modified by two nearby
      amino acids.

PMID- 11294400
TI  - Telemedicine: a solution to the followup of rural trauma patients?
AB  - BACKGROUND: Outpatient followup of rural trauma patients is problematic for
      physicians and patients. Our hypothesis was that telemedicine-based followup of
      trauma patients discharged to remote areas is feasible and is associated with
      high patient and physician satisfaction. STUDY DESIGN: We chose 11 counties in
      Kentucky surrounding a remote telemedicine site as our region of interest. Any
      adult trauma patient who was discharged from our Level I trauma center to this
      geographic region was eligible to have routine followup appointment(s) at the
      TeleTrauma Clinic. Patients were examined and interviewed with the assistance of
      a nurse, an electronic stethoscope, and a close-up imaging instrument.
      Radiographs performed at the telemedicine site were viewed. Patients and
      physicians completed a survey after the appointment. RESULTS: To date, we have
      conducted 22 telemedicine-based followup assessments of trauma patients. The
      average age and Injury Severity Score were 42 years and 18, respectively. Plain
      radiographs were reviewed in 13 cases. Our patient surveys indicated a high
      degree of satisfaction with the teleappointment. In 15 of 22 patients, no further
      clinical followup was arranged. The differences in travel distances and times for
      an appointment at the TeleTrauma Clinic versus an appointment at our Level I
      trauma center were significant. The average and median duration of the
      appointments was 14 minutes. All telemedicine encounters were done by two
      physicians, who recorded a high level of satisfaction. CONCLUSIONS: Our early
      experience with the outpatient followup of remote trauma victims by telemedicine
      is encouraging. Patient surveys indicate a high degree of satisfaction. As a
      result of our favorable experience, telemedicine-based followup may be expanded
      to other regions of Kentucky.

PMID- 11294401
TI  - National practice patterns of sentinel lymph node dissection for breast
      carcinoma.
AB  - BACKGROUND: The sentinel node is the first regional lymph node to receive tumor
      cells that metastasize through the lymphatic channel from a primary tumor. The
      tumor status of the sentinel node should reflect the tumor status of the entire
      regional node basin. Sentinel lymph node dissection (SLND) has recently been
      investigated for use in patients with early breast carcinoma to avoid the
      sequelae of complete axillary lymph node dissection (ALND). Published studies of
      SLND in breast cancer patients identify marked variations in technique, and there
      are few guidelines for credentialing surgeons to perform SLND. STUDY DESIGN: The
      purpose of this study was to assess the current practice of SLND for breast
      cancer in the United States. A 27-item questionnaire was mailed to 1,000 randomly
      selected Fellows of the American College of Surgeons. Responses were anonymous.
      Statistical analysis was performed using SAS software (SAS Institute, Cary, NC).
      RESULTS: Response rate was 41% (n = 410), and 77% of those who responded
      performed SLND for breast cancer. The majority (60%) of surgeons responding
      routinely ordered preoperative lymphoscintigraphy. Of those who did
      lymphoscintigraphy, 28% removed internal mammary lymph nodes when
      lymphoscintigraphy showed drainage to these nodes. Ninety percent of surgeons
      used both blue dye and radiocolloid. Eighty percent of centers responding
      performed routine immunohistochemistry on sentinel lymph nodes, and 15% performed
      reverse transcription polymerase chain reaction. Ninety-six percent of surgeons
      performed SLND for primary tumors 5 cm or smaller, and 95% performed SLND for an
      excisional cavity 6 cm and smaller. Twenty-eight percent performed SLND for high
      grade ductal carcinoma in situ, and 28% of respondents performed 10 or fewer SLND
      procedures with subsequent ALND before performing SLND alone. Surgeons learned
      SLND through courses (35%), oncology fellowships (26%), observation of other
      surgeons (31%), or were self-taught (26%). CONCLUSIONS: The majority of surgeons
      in the United States use similar technique for SLND breast cancer. But, there was
      marked variation in the number of SLND cases validated by an ALND before
      performing SLND only.

PMID- 11294402
TI  - Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single
      institution experience.
AB  - BACKGROUND: Thymectomy has become recognized as an integral element in the care
      of the patient with myasthenia gravis. Although the number of elderly patients
      with myasthenia is substantial, little data exist demonstrating the efficacy and
      morbidity of thymectomy in this population. STUDY DESIGN: We retrospectively
      analyzed 126 cervicomediastinal thymectomies performed at a single university
      hospital from 1980 to 1998. Patients 55 years or older were compared with those
      less than 55. Efficacy was measured by determining the change in Osserman score,
      the rate of remission during followup, and the reduction in medication
      requirements after thymectomy. RESULTS: Older patients (n = 28) had similar
      Osserman scores (p = 0.8) and similar rates of complete and partial remission as
      the younger group (n = 98) at a mean +/- SEM followup of 58 +/- 5 months. The two
      groups did not differ in the number (p = 0.4) and doses of medications used to
      control myasthenic symptoms after operation. Older age was associated with an
      increased length of hospitalization (13.8 +/- 3.2 days versus 9.7 +/- 0.6 days, p
      = 0.05) and a higher incidence of reintubation, and longer ventilatory support
      (2.6 +/- 1.3 days versus 0.1 +/- 0.1 days, p = 0.001). CONCLUSIONS: Increased age
      does not alter the outcomes of thymectomy for myasthenia gravis. Older patients
      can expect to have similar responses and require a similar number of
      postoperative medications as younger patients, but with a higher short-term
      morbidity.

PMID- 11294399
TI  - The birth of clinical organ transplantation.

PMID- 11294403
TI  - Predictive risk factors for postoperative tetany in female patients with Graves'
      disease.
AB  - BACKGROUND: Postoperative tetany occurs in patients with secondary
      hyperparathyroidism caused by a deficiency in calcium and vitamin D concomitant
      with transient hypoparathyroidism induced by surgery. In the present study, we
      further clarified the risk factors by referring to serum 25-hydroxyvitamin D
      [25(OH)D] and alkaline phosphatase. STUDY DESIGN: The serum levels of intact
      parathyroid hormone, calcium and other electrolytes, and 25-hydroxyvitamin D
      [25(OH)D] were measured preoperatively in 178 female patients with Graves'
      disease who underwent subtotal thyroidectomy. RESULTS: Of the 178 female
      patients, 15 (8.4%) developed tetany. Univariate analysis of 16 possible risk
      factors showed that 2 were statistically significant: serum 25(OH)D and alkaline
      phosphatase levels. The incidence of tetany according to the serum levels of
      25(OH)D and alkaline phosphatase was 19.1% (9/47) in patients with 25(OH)D < or =
      25 nmol/L and alkaline phosphatase > 155, 11.8% (4/34) in those with 25(OH)D < or
      = 25 nmol/L and alkaline phosphatase < or = 155, 6.7% (2/30) in those with
      25(OH)D > 25 nmol/L and alkaline phosphatase > 155, and 0% (0/50) in those with
      25(OH)D > 25 nmol/L and alkaline phosphatase < or = 155. CONCLUSIONS: Patients
      with Graves' disease who have vitamin D deficiency with high serum alkaline
      phosphatase levels are the highest-risk group for postoperative tetany. Serum
      25(OH)D and alkaline phosphatase should be monitored in patients with Graves'
      disease.

PMID- 11294404
TI  - Comparison of pulmonary function and postoperative pain after laparoscopic versus
      open gastric bypass: a randomized trial.
AB  - BACKGROUND: Impairment of pulmonary function is common after upper abdominal
      operations. The purpose of this study was to compare postoperative pulmonary
      function and analgesic requirements in patients undergoing either laparoscopic or
      open Roux-en-Y gastric bypass (GBP). STUDY DESIGN: Seventy patients with a body
      mass index of 40 to 60 kg/m2 were randomly assigned to undergo laparoscopic (n =
      36) or open (n = 34) GBP. The two groups were similar in age, gender, body mass
      index, pulmonary history, and baseline pulmonary function. Pulmonary function
      studies were performed preoperatively and on postoperative days 1, 2, 3, and 7.
      Oxygen saturation and chest radiographs were performed on both groups
      preoperatively and on postoperative day 1. Postoperative pain was evaluated using
      a visual analog scale and the amount of narcotic consumed was recorded. Data are
      presented as mean +/- standard deviation. RESULTS: Laparoscopic GBP patients had
      significantly less impairment of pulmonary function than open GBP patients on the
      first three postoperative days (p < 0.05). By the 7th postoperative day, all
      pulmonary function parameters in the laparoscopic GBP group had returned to
      within preoperative levels, but only one parameter (peak expiratory flow) had
      returned to preoperative levels in the open GBP group. On the first postoperative
      day, laparoscopic GBP patients used less morphine than open GBP patients (46 +/-
      31 mg versus 76 +/- 39 mg, respectively, p < 0.001), and visual analog scale pain
      scores at rest and during mobilization were lower after laparoscopic GBP than
      after open GBP (p < 0.05). Fewer patients after laparoscopic GBP than after open
      GBP developed hypoxemia (31% versus 76%, p < 0.001) and segmental atelectasis (6%
      versus 55%, p = 0.003). CONCLUSION: Laparoscopic gastric bypass resulted in less
      postoperative suppression of pulmonary function, decreased pain, improved
      oxygenation, and less atelectasis than open gastric bypass.

PMID- 11294405
TI  - Three spectra of laparoscopic entry access injuries.
AB  - BACKGROUND: Procedure-based surveys oflaparoscopic entry access injuries show a
      reassuringly low incidence, varying from 5 per 10,000 to 3 per 1,000, and,
      consequently, can provide only limited specific injury data. The current study
      uses existing injury-based reporting systems to access a uniquely large number of
      entry injuries to define the nature and outcomes of such events. STUDY DESIGN:
      Claims arising from US and non-US entry access injuries, between 1980 and 1999,
      reported to the Physicians Insurers Association of America by their member and
      affiliate companies and entry-injury medical device reports to the US FDA, from
      1995 through October 1997, were analyzed to determine operative procedures,
      physician specialties, entry devices, and techniques associated with specific
      injuries. Individual injuries were analyzed for their relative incidence and
      potential to cause disability and death. RESULTS: Five hundred ninety-four
      structures or organs were injured in 506 patients, resulting in 65 deaths (13%).
      General surgical procedures made up at least 67% of combined medical device
      reports and US Physicians Insurers Association of America cases, and gynecologic
      procedures accounted for 63% of non-US claims. Bowel and retroperitoneal vascular
      injuries comprised 76% of all injuries incurred in the process of establishing a
      primary port. Nearly 50% of both small and large bowel injuries were unrecognized
      for 24 hours or longer. Delayed recognition, along with age greater than 59 years
      and major visceral vascular injuries, were each independent significant
      predictors of death. CONCLUSIONS: No entry technique or device is absolutely
      safe. Avoidance of entry injuries depends on patient-specific anatomic
      orientation and control of entry axial force. Certain entry devices can be
      facilitating in controlling axial force. Overall, this large aggregate of entry
      access injuries shows them to be more serious and, along with other data, implies
      that they might be more common than reported in procedure-based studies.

PMID- 11294406
TI  - Effectiveness of laparoscopic cadaveric dissection in enhancing resident
      comprehension of pelvic anatomy.
AB  - BACKGROUND: Anatomic instruction during preclinical years of medical school has
      been in decline recently. There is evidence that residents already lose a
      considerable portion of basic anatomic knowledge in the transition from student
      to clinician, and this deficit is even more dramatic in residents who start their
      training with a decreased understanding of anatomy. We questioned whether anatomy
      could be adequately retaught to new residents as surgical anatomy. In an effort
      to address this deficiency, we developed a program to teach pelvic anatomy in
      fresh cadavers using a laparoscopic approach. The purpose of this investigation
      is to determine if such a program is effective in enhancing residents' pelvic
      anatomy comprehension. STUDY DESIGN: An obstetrics and gynecology residency was
      divided into intervention (n = 15) and control (n = 13) groups. The intervention
      was a 4-hour laparoscopic dissection in a fresh cadaver. Outcomes measures
      included a multiple-choice test, practical exam, faculty evaluation, and
      satisfaction assessment. The faculty evaluation and satisfaction assessment used
      a visual analog scale. Univarate and nonparametric analysis were used when
      appropriate. RESULTS: Initial test scores (p = 0.32), faculty evaluations (p =
      0.25), and satisfaction scores (p = 0.17) were similar. Both groups improved
      their anatomic knowledge based on test scores (p = 0.004) and faculty evaluations
      (p < 0.001), and final test scores were not significantly different (p = 0.19).
      Data measured on a 10-cm visual analog scale suggested higher faculty evaluations
      in the intervention group (14mm versus 10.3mm, (p = 0.23). Similarly there were
      higher scores on the cadaver test in the intervention group (65% versus 50%), (p
      = 0.13). The intervention group was significantly more satisfied with their
      anatomic training (16.1 mm versus-10.1 mm, p = 0.001). CONCLUSIONS: This study
      did not have sufficient power to demonstrate that a single laparoscopic cadaveric
      dissection improves cognitive measures of anatomic perception, but suggested that
      it improves spatial perception of anatomy and is perceived by residents to be a
      valuable educational approach.

PMID- 11294407
TI  - Operative treatment for chronic pancreatitis pain.
AB  - BACKGROUND: Management of pain is the most frustrating problem associated with
      chronic pancreatitis. Pain is progressive and difficult to quantify.
      Uncontrolled, it eventually destroys the patient's quality of life, leading to
      drug addiction. STUDY DESIGN: This study reports the results of 258 operations on
      239 consecutive patients treated for pain related to chronic pancreatitis between
      1969 and 1999. The operations performed were 42 pancreaticoduodenectomies, 48
      side-to-side pancreaticojejunostomies, 68 distal pancreatectomies, 21 85% to 95%
      distal pancreatectomies, 70 cystenterostomies and 9 sphincteroplasties. Efforts
      were made to choose the operation most appropriate for the pathological
      conditions encountered in each patient. Results of treatment were satisfactory if
      patients were entirely relieved of pain and unsatisfactory if there was any
      residual pain. Presence or absence of pain was based on patient's own evaluation
      at the time of their last followup examination. RESULTS: Results were overall
      satisfactory in 71% of patients after pancreaticoduodenectomy, 68% after side-to
      side pancreaticojejunostomy, 69% after distal pancreatectomy; 69% after 85% to
      95% distal pancreatectomy, 51% after cystenterostomy, and 44% after
      sphincteroplasty. The mean followup of patients was 4 y (range 0 to 23 y).
      CONCLUSIONS: The cause of chronic pancreatitis is obscure. As a consequence,
      there have been few advances in the treatment of this condition. There are new
      techniques to resect the pancreas, but the results are little better than those
      obtained with older methods. Advances in the treatment of chronic pancreatic pain
      will come from knowledge concerning its cause. Discovery of mechanisms
      stimulating the pathways that lead to the perception of pain and methods for
      interruption of these mechanisms may provide new treatments.

PMID- 11294408
TI  - Small-for-size grafts in living-related liver transplantation.
AB  - BACKGROUND: The problems associated with small-for-size grafts in living-related
      liver transplantation are not fully understood. STUDY DESIGN: A consecutive
      series of 79 patients underwent 80 living-related liver transplantation
      procedures, including one retransplant, at the University of Tokyo from January
      1996 to January 2000. They were divided into two groups by graft size: graft
      weight/recipient standard liver volume ratios of 40% or less (n = 24), and more
      than 40% (n = 56). Preoperative status, mortality, morbidity, duration of
      hospital stay, and postoperative graft function were examined and compared
      between the groups. RESULTS: The rate of patients who were restricted to the
      intensive care unit preoperatively was comparable between the groups (33% versus
      21%, p = 0.27). The mean standard liver volume ratios were 37% in the small graft
      group and 84% in the large group. Survival rates were 80% (5 of 24) for the small
      graft group, which was significantly lower than that for the large group (96%, 54
      of 56, p = 0.02). The rate of acute rejection was comparable between the groups
      (33% versus 43%, p = 0.47). Vascular complication was observed in 17% of the
      small graft group patients and 23% of the large group (p = 0.77). No difference
      was observed in the frequency of bile leakage or bile duct stenosis (25% versus
      21%, p=0.77). Hyper-bilirubinemia and elongation of prothrombin time persisted
      longer in the small graft group than in the large group (p < 0.0001 for both).
      CONCLUSIONS: Our surgical results may suggest that a graft weight ratio of 40% or
      less provides a lower chance of survival after living-related liver
      transplantation.

PMID- 11294409
TI  - A contemporary neurosurgical approach to sport-related head injury: the McGill
      concussion protocol.

PMID- 11294410
TI  - Abdominal access complications in laparoscopic surgery.

PMID- 11294411
TI  - The Gibraltar sign.

PMID- 11294412
TI  - Appendiceal intussusception.

PMID- 11294413
TI  - Left side first: a different approach for teaching laparoscopic Nissen
      fundoplication.

PMID- 11294414
TI  - Breast lymphatic mapping using subareolar injections of blue dye and
      radiocolloid: illustrated technique.

PMID- 11294415
TI  - Portal vein thrombosis after splenectomy.

PMID- 11294416
TI  - Palliation of proximal gastric cancer.

PMID- 11294417
TI  - Minimally invasive disc surgery: a review.

PMID- 11294418
TI  - The co-expression of p53 protein and P-glycoprotein is correlated to a poor
      prognosis in osteosarcoma.
AB  - Multidrug resistance (MDR), mediated by P-glycoprotein (P-gp), is an in vitro
      phenomenon observed within tumour cells, suggesting cross-resistance to unrelated
      drugs, and expression of P-gp may therefore affect the prognosis and incidence of
      recurrence after treatment. The mutant p53 protein causes reduced tumour
      suppression. Co-expression of p53 and P-gp is related to short survival,
      increased tumour activity and drug resistance. The purpose of this study was to
      measure the expression of p53 protein and P-gp in osteosarcoma tissue and assess
      its prognostic significance. Fifty-two tumour specimens were evaluated. The
      correlation between p53 and P-gp expression was significant (P=0.0008). In
      univariate analysis of survival, p53 protein was not significant (P=0.2) but P-gp
      was significant (P=0.0001). The co-expression of p53 and P-gp was the strongest
      indicator of a short survival according to multivariate analysis (P=0.0004).

PMID- 11294419
TI  - Pelvic limb-salvage surgery for malignant tumors.
AB  - Thirteen patients with primary malignant tumors of the pelvis underwent internal
      hemipelvectomy. The diagnoses were: Ewing's sarcoma 7, osteosarcoma 4,
      chondrosarcoma 1, and malignant fibrous histiocytoma 1. No megaprostheses or
      massive allografts were used for reconstruction. Six patients underwent resection
      only with no reconstruction, 5 had strut grafts inserted to restore the pelvic
      ring, 1 had an autoclaved autograft of the acetabulum and 1 had an ilio-femoral
      arthrodesis. No patients were lost to follow-up. Nine patients died from their
      disease after an average of 23 months (range 2 to 72 months). The 4 survivors (3
      free of disease) have an average follow-up of 84 months (range 60 to 120 months).

PMID- 11294420
TI  - Failure after core decompression in osteonecrosis of the femoral head.
AB  - In a retrospective study of 39 hips with osteonecrosis of the femoral head
      treated with core decompression we evaluated the extent of the necrotic area, the
      Ficat stage and the location of the lesion. The extent of the necrotic lesion was
      classified into three categories: mild, less than 15%; moderate, 15-30%; and
      severe, more than 30%. In 14 mild cases core decompression failed in 2, whereas
      there were 4 failures out of 7 moderate cases and 16 failures out of 19 severe
      cases. The extent and location of the necrotic portion as well as the Ficat stage
      can be used as predictors for the result of core decompression in osteonecrosis
      of the femoral head.

PMID- 11294421
TI  - Massive structural allograft in revision of septic hip arthroplasty.
AB  - We reviewed 10 patients who had undergone two-stage reconstruction with massive
      structural allografts following failure of hip arthroplasty due to infection. The
      mean follow-up time was more than 5 years (range 3-10 years). There was no case
      of the infection recurring. The most common pathogen isolated at the time of
      first-stage surgery was Stalphylococcus epidermnidis. The mean preoperative
      modified Harris Hip score was 27.4 (range 9-58) and the mean postoperative score
      was 73.5 (range 53-92) with a mean increase in the score of 46.1 points. One
      patient required revision of the acetabular cup for aseptic loosening and another
      had a dislocation, which was stable after manual reduction. We conclude that the
      use of a massive structural allograft in revision of septic hip arthroplasty is a
      viable option.

PMID- 11294422
TI  - Heterotopic ossification after total hip arthroplasty.
AB  - We studied 178 patients undergoing total hip arthroplasty (66 men and 112 women)
      retrospectively, with regard to the incidence and severity of heterotopic
      ossification and the significance of postoperative prophylaxis with non-steroid
      anti-inflammatory drugs. The overall incidence of heterotopic ossification was
      32% 1 year after surgery. The factors increasing the incidence were male gender,
      previous arthroplasty of the contralateral hip joint, previous surgery on the
      hip, absence of preoperative treatment with non-steroidal anti-inflammatory drugs
      and an operating time of more than 100 min. The incidence of heterotopic
      ossification was lower in the patients of O blood group.

PMID- 11294423
TI  - Modified Loeffler's medial capsulotomy for osteoarthritis of the knee: 20 years'
      follow-up.
AB  - We reviewed 11 knees in ten patients at a mean follow-up of 23 years after a
      modified Loeffler's medial capsulotomy for osteoarthritis of the knee. The mean
      age was 59+/-8 years at surgery. The mean knee score (Hospital for Special
      Surgery) was 59 points before surgery and 79 points at follow-up. The long-term
      results of this operation were thus maintained over a prolonged period. This is a
      relatively simple procedure, which may be performed in the elderly, with
      satisfactory long-term results.

PMID- 11294424
TI  - Patellar height after high tibial osteotomy.
AB  - We analysed two series of patients affected by unicompartmental arthrosis or
      axial malalignment of the knee treated with two different techniques of high
      tibial osteotomy. Forty-seven knees were treated with a closing wedge osteotomy
      (CWO) and 40 with an opening wedge osteotomy (OWO). The two groups were
      comparable with respect to age, gender and deformity. For each patient the
      patellar height was measured by Caton's method before surgery, and at the latest
      assessment (at least 1 year after operation). The correction rate for the two
      series was analysed to assess any possible correlation between the variation of
      the patellar height and the degree of correction of the knee axis. We concluded
      that a high tibial osteotomy modifies the patellar height and that this depends
      on the technique employed. Patellar 'lowering' occurred more often with OWO than
      with CWO and the latter also produced a high degree of patellar elevation.

PMID- 11294425
TI  - Anatomical aspects of biopsy of the proximal fibula.
AB  - The relationship between the peroneal nerves and the anatomical structures near
      the fibular head were studied in 20 cadavers. It was the purpose to define the
      boundaries of a "safe" area when performing a biopsy of the fibular head. The
      distances between the proximal end of the fibular head and the deep peroneal
      nerve (26+/-0.32 mm) and the intermuscular septum (15+/-0.19 mm) were measured,
      as well as the angle between the deep peroneal nerve and the fibula as seen in
      the A-P view (23.5+/-3.5 degrees). We considered that biopsies should be
      performed with an anterolateral approach in the safe area formed by the fibular
      head and the deep peroneal nerve in the anterior compartment.

PMID- 11294426
TI  - Primary unreamed intramedullary nailing for open fractures of the tibia.
AB  - Forty-six open tibial fractures (42 patients) were treated by primary unreamed
      intramedullary nailing, with debridement of open wounds and treatment of soft
      tissue. According to Gustilo-Anderson classification there were 18 grade I cases,
      18 grade II cases and 10 grade III cases. The incidence of infection was low with
      two cases of superficial infection and one of deep infection. The mean time for
      union was 21.9 weeks and the rate of nonunion was 10.8%. There was no significant
      difference in the mean time to union, infection rate and rate of nonunion with
      different site and grade of fracture, but there was a longer union time and a
      higher rate of nonunion in complex and comminuted fractures. Unreamed
      intramedullary nailing, with appropriate soft tissue treatment, gives good
      results in the treatment of open tibial fractures including grade III.

PMID- 11294427
TI  - Long-term quadriceps femoris functional deficits following intramedullary nailing
      of isolated tibial fractures.
AB  - This retrospective study assessed 5 male and 5 female patients, age 35.1+/-16
      years, height 171.8+/-12 cm, and weight 75.5+/-18 kg (mean+/-SD) who were more
      than 1 year post isolated tibial fracture (18+/-6 months) and had been treated
      with an intramedullary tibial nail. Subjects completed a 12-question visual
      analog scale, a physical symptom and activity of daily living survey, and were
      also tested for bilateral isokinetic (60 degrees/s) quadriceps femoris and
      hamstring strength. Knee pain during activity, stiffness, swelling, and buckling
      were the primary symptomatic complaints. Perceived functional task deficits were
      greatest for climbing or descending stairs, pivoting, squatting, and walking on
      uneven surfaces. Involved lower extremity knee extensor and flexor torque
      production deficits were 25% and 17%, respectively. Early rehabilitation focuses
      on maintaining adequate operative site bony fixation while providing controlled,
      progressive, and regular biomechanical loading to restore functionally competent
      tissue. Following adequate fracture healing, greater emphasis should be placed on
      lower extremity functional recovery including commonly performed activities of
      daily living and other functional tasks that are relevant to the patient's
      disability level. A cyclic rehabilitation program that progresses the weight
      bearing environment to facilitate bone and soft tissue healing and neuromuscular
      re-education is proposed.

PMID- 11294428
TI  - The pneumatic tourniquet in arthroscopic surgery of the knee.
AB  - In a randomized study 56 patients undergoing arthroscopic surgery of the knee
      were randomly allocated to one of 2 groups: surgery with a tourniquet and surgery
      without a tourniquet. No significant difference was found between the 2 groups
      with regard to operating times, technical intraoperative difficulties,
      identification of intraarticular structures, postoperative pain or postoperative
      complications. In neither group was the procedure abandoned due to technical
      difficulties. The pain scores in the non-tourniquet group were lower than those
      in the group of patients operated on with the use of a pneumatic tourniquet. The
      study suggests that the use of a tourniquet in arthroscopic surgery of the knee
      is unnecessary.

PMID- 11294429
TI  - Rehabilitation after arthroscopic meniscectomy: a critical review of the clinical
      trials.
AB  - We reviewed the literature on patient management following arthroscopic meniscal
      surgery. A critical appraisal of the literature produced 8 randomized controlled
      trials evaluating the use of non-steroidal anti-inflammatory drugs or various
      forms of physiotherapy and pain control. Different treatments and outcome
      measures precluded meta-analysis. The limited evidence suggests that this is a
      relatively pain-free procedure with rapid recovery, and that in most cases simple
      analgesia in the first 1-2 days following surgery and a well-planned home-based
      exercise program should be sufficient. It is possible that routine daily non
      steroidal anti-inflammatory drugs post-operatively for 3-6 weeks may enhance
      recovery rates. One study found that physiotherapy was beneficial for regaining
      muscle strength and on pain assessment but this did not translate into functional
      improvement. Descriptive studies are required to ascertain the types and duration
      of treatments being offered to patients after arthroscopic meniscectomy. Further
      research is needed to perform well-designed studies of current treatments that
      take into account predisposing factors and their impact on outcome, including use
      of prerandomization and real-life functional outcome measures.

PMID- 11294430
TI  - Non-operative treatment of multidirectional shoulder instability.
AB  - At an average follow-up of 3.7 years we assessed the results of non-operative
      treatment of 84 symptomatic shoulders in 59 patients with a diagnosis of
      multidirectional shoulder instability. Sixty-two shoulders had received no
      previous surgical treatment (group A) while 22 had failed to respond to surgical
      treatment before the rehabilitation programme (group B). Subjectively 11 of the
      non-operated shoulders (group A) were cured and 27 improved, 23 of the shoulders
      remained the same and one was worse at follow-up. According to the age and gender
      adjusted Constant score, 38 of the non-operated shoulders had either no
      disability or only mild disability, nine had moderate disability, while the
      remaining 15 had severe or total disability. These figures were far worse in
      group B. In group A only four shoulders required operation, while in group B
      seven required operation following rehabilitation. Patients who had had previous
      shoulder surgery, those with a work related injury and those with psychological
      problems were less likely to benefit from the rehabilitation programme.

PMID- 11294431
TI  - Plaster cast compared with bridging external fixation for distal radius fractures
      of the Colles' type.
AB  - We compared two different treatments for displaced distal radius Colles' type
      fractures (Older type 3 and 4), at two hospitals. We found bridging external
      fixation superior to reduction and fixation in a dorsal plaster cast regarding
      both the end-anatomic results at 3 months and the functional scores at 3 and 9
      months (modified Gartland and Werley).

PMID- 11294432
TI  - Endoscopic carpal tunnel release and nerve conduction studies.
AB  - We investigated the outcome of endoscopic carpal tunnel release (ECTR) for
      patients with carpal tunnel syndrome (CTS) in comparison with the results of
      preoperative nerve conduction studies. The compound muscle action potential
      (CMAP) of the abductor pollicis brevis muscle (APB) and the second lumbrical
      muscle (L2) was recorded following median nerve stimulation at the wrist. A total
      of 38 hands in 35 patients were classified into four categories. Hands with a
      similarly prolonged distal motor latency for the APB and L2 were classified as
      type I (n=25), while those with a more prolonged distal motor latency for the APB
      than for the L2 (>0.7 ms) were classified as type 2 (n=10). Hands with a CMAP for
      the APB, but not L2, were classified as type 3 (n=1), and hands with no CMAP for
      either the APB or L2 were classified as type 4 (n=2). After ECTR, all of the type
      1 and 2 hands were improved. Patients with type 3 and type 4 hands did not show
      satisfactory improvement, which may have been due to anatomical variation of the
      recurrent motor branch of the median nerve.

PMID- 11294433
TI  - Avulsion fractures of the anterior inferior iliac spine: the case for surgical
      intervention.
AB  - Two cases of avulsion fracture of the anterior inferior iliac spine are reported.
      One was a missed diagnosis that resulted in exostosis formation needing excision.
      The second case was an adolescent with significant displacement of the fragment
      and a primary open reduction and internal fixation was done. A high index of
      suspicion is necessary to diagnose this relatively rare injury and surgery has a
      role in carefully selected cases.

PMID- 11294434
TI  - Conjoint recognition and phantom recollection.
AB  - A new methodology for measuring illusory conscious experience of the
      "presentation" of unstudied material (phantom recollection) is evaluated that
      extracts measurements directly from recognition responses, rather than indirectly
      from introspective reports. Application of this methodology in the Deese-Roediger
      McDermott (DRM) paradigm (Experiments 1 and 2) and in a more conventional
      paradigm (Experiment 3) showed that 2 processes (phantom recollection and
      familiarity) contribute to false recognition of semantically related distractors.
      Phantom recollection was the larger contributor to false recognition of critical
      distractors in the DRM paradigm, but surprisingly, it was also the larger
      contributor to false recognition of other types of distractors. Variability in
      false recognition was tied to variability in phantom recollection. Experimental
      control of phantom recollection was achieved with manipulations that were
      motivated by fuzzy-trace theory's hypothesis that the phenomenon is gist-based.

PMID- 11294435
TI  - Are emotionally charged lures immune to false memory?
AB  - Using the Deese-Roediger-McDermott task and E. Tulving's (1985) remember-know
      judgments for recognition memory, the authors explored whether emotional words
      can show the false memory effect. Participants studied lists containing
      nonemotional, orthographic associates (e.g., cape, tape, ripe; part, perk, dark)
      of either emotional (e.g., rape) or nonemotional (e.g., park) critical lures.
      This setup produced significant false "remembering" of emotional lures, even
      though initially no emotional words appeared at study. When 3 emotional nonlure
      words appeared at study, emotional-lure false recognition more than doubled.
      However, when these 3 study words also appeared on the recognition test, false
      memory for the emotional lures was reduced. Across experiments, participants
      misremembered nonemotional lures more often than they did emotional lures, but
      they were more likely to rate emotional lures as "remembered," once they had been
      recognized as "old." The authors discuss findings in light of J. J. Freyd and D.
      H. Gleave's (1996) criticisms of this task.

PMID- 11294436
TI  - Modality effects in false recall and false recognition.
AB  - R. E. Smith and R. R. Hunt (1998) reported a dramatic reduction in false
      remembering in a list-learning paradigm by switching from auditory to visual
      presentation at study. The current authors replicated these modality effects
      using written recall and visual recognition tests but obtained smaller effects
      than those in R. E. Smith and R. R. Hunt's study. In contrast, no modality effect
      occurred on auditory recognition tests. Manipulating study and test modality
      within-subjects (Experiment 2) and between-subjects (Experiment 3) yielded
      similar results. It was also found that subjects frequently judged critical
      nonstudied words as having been presented in the modality of their corresponding
      study lists. The authors concluded that subjects could retrieve distinctive
      information about a study list's presentation modality to reduce false
      remembering but only did so under certain conditions. The modality effect on
      false remembering is a function of both encoding and retrieval factors.

PMID- 11294437
TI  - P300 latency, but not amplitude or topography, distinguishes between true and
      false recognition.
AB  - Two experiments are described in which the P300 component of the event-related
      potential was recorded during a modification of the Deese-Roediger-McDermott
      false-memory paradigm. P300 amplitudes and topographies were evaluated in both
      true recognition of previously presented (studied) words and in false recognition
      of associatively related, never presented (critical lure) words. P300 topography
      and amplitude did not appear to differ between true and false recognition.
      However, false recognition of critical lures produced substantially shorter P300
      latencies than did the true recognition of studied words.

PMID- 11294438
TI  - The use of source memory to identify one's own episodic confusion errors.
AB  - In 4 category cued recall experiments, participants falsely recalled nonlist
      common members, a semantic confusion error. Errors were more likely if critical
      nonlist words were presented on an incidental task, causing source memory
      failures called episodic confusion errors. Participants could better identify the
      source of falsely recalled words if they had deeply processed the words on the
      incidental task. For deep but not shallow processing, participants could reliably
      include or exclude incidentally shown category members in recall. The illusion
      that critical items actually appeared on categorized lists was diminished but not
      eradicated when participants identified episodic confusion errors post hoc among
      their own recalled responses; participants often believed that critical items had
      been on both the incidental task and the study list. Improved source monitoring
      can potentially mitigate episodic (but not semantic) confusion errors.

PMID- 11294439
TI  - False recognition occurs more frequently during source identification than during
      old-new recognition.
AB  - A number of recent reports have investigated false memories using variants of the
      Deese-Roediger-McDermott (DRM) paradigm. Because these false memories have been
      difficult to eliminate, this study investigated whether false recognition could
      be reduced by incorporating source-monitoring criteria into decision processes.
      Making claims about the manner in which items were learned should require more
      careful scrutiny of memories, and therefore false recognition should be minimized
      with source instructions as compared with old-new recognition instructions. In 3
      experiments that varied the combination of sources, false recognition was
      increased rather than reduced by applying source-monitoring processes. The
      theoretical implications of these counterintuitive results are discussed in terms
      of the old-new detection component of source judgments.

PMID- 11294440
TI  - Retrieval processes in recognition and cued recall.
AB  - The present studies used response time (RT) and accuracy to explore the processes
      and relation of recognition and cued recall. The studies used free-response and
      signal-to-respond techniques and varied list length and presentation rate. In
      Experiment 1, the free-RT distributions for recognition had much lower mean and
      variance than those for cued recall. Similarly, signal-to-respond curves showed
      fast rates of accumulation of information in recognition and slow rates in
      recall. (Quantitative models of the results are presented in the companion
      article by D. E. Diller, P. A. Nobel, and R. M. Shiffrin, 2001). To rule out the
      possibility that the slower responses in cued recall were due to a fast retrieval
      process followed by a slow process of cleaning up the retrieved trace for output,
      additional signal-to-respond tasks provided the relevant alternatives at test.
      Yet, these conditions showed slow growth rates, similar to those seen in recall.
      The results support the hypothesis that retrieval processes differ for single
      item recognition and cued recall, with retrieval in cued recall (and associative
      recognition) due to a sequential search.

PMID- 11294441
TI  - An ARC-REM model for accuracy and response time in recognition and recall.
AB  - This article presents a model for accuracy and response time (RT) in recognition
      and cued recall, fitted to free-response and signal-to-respond data from
      Experiment 1 of P. A. Nobel and R. M. Shiffrin (2001). The model posits that
      recognition operates through parallel activation in a single retrieval step and
      cued recall operates as a sequential search. Because the data for recognition
      showed that variations in list length and study time per list had a large effect
      on accuracy but a small or negligible effect on (a) free-response RT
      distributions and (b) retrieval dynamics in signal-to-respond, the timing of the
      recognition decision is based on an assessment of retrieval completion (ARC),
      rather than on a sufficiency of evidence in favor of 1 of the response options.
      By assuming within-trial forgetting, the model predicts both the dissociation of
      accuracy and RT and the finding that errors are slower than correct responses.
      For cued recall, this model was incorporated as the 1st step in a search
      consisting of cycles of sampling and recovery.

PMID- 11294442
TI  - Generation and hypermnesia.
AB  - The multifactor account of the generation effect makes detailed predictions about
      the effects of generation on item-specific and relational encoding, predictions
      confirmed in four experiments using a multiple-test methodology. In pure-list
      designs with unrelated study items, generation produced more interest item gains
      (indexing greater item-specific processing) and more interest item losses
      (indexing less relational processing) relative to the read condition. In a mixed
      list design, generation produced more gains but did not affect losses. With
      categorically-related study items, generation produced more gains but fewer
      losses (indicating enhanced relational encoding). Generation consistently
      produced hypermnesia whereas reading did so only for related study items. Also, a
      significant generation effect emerged on later tests under conditions (between
      subjects design, unrelated study items) which typically yield no generation
      effect.

PMID- 11294443
TI  - Interference between cognitive skills.
AB  - This study used a novel task, clock arithmetic, and a classic A-B/A-Br transfer
      design to investigate the presence of interference between cognitive skills. The
      A-B/A-Br design required participants to first learn problem-to-answer
      associations during training and then to learn new pairings between the same
      problems and answers during transfer. The associations learned during training
      interfered with those learned during transfer, as measured by slowed reaction
      times to emit the correct response, failures to retrieve any response, and
      intrusion errors. Interference persisted even after a 1-week retention interval
      and was especially prevalent during the warm-up period at the beginning of the
      retention test. The use of the A-B/A-Br design indicates that whether an
      incorrect answer retrieved from memory is emitted as a response depends on
      whether the intrusion is recognized as inappropriate for the current task. The
      long-term memory for cognitive skills means that attempts to learn new responses
      to old stimuli will be plagued by persistent intrusion errors.

PMID- 11294444
TI  - Irrelevant response effects improve serial learning in serial reaction time
      tasks.
AB  - Tones were introduced into a serial reaction time (SRT) task to serve as
      redundant response effects. Experiment 1 showed that the tones improved serial
      learning with a 10-element stimulus sequence, but only if the tone effects were
      mapped onto the responses contingently. Experiment 2 demonstrated that switching
      to noncontingent response-effect mapping increased SRT only when participants had
      previously adapted to contingent response-effect mapping. In Experiment 3, the
      beneficial influence of contingent tone effects on serial learning occurred only
      when there was sufficient time between the response effects and the next
      imperative stimuli. The results are discussed in terms of the ideomotor
      principle. It is claimed that an internal representation of the to-be-produced
      tone effects develops and gains control over the execution of the response
      sequence.

PMID- 11294445
TI  - Implicit learning of first-, second-, and third-order transition probabilities.
AB  - Most sequence-learning studies have confounded different types of information,
      making it difficult to know precisely what is learned. Addressing many of the
      confounds, the current study shows that people can learn 1st-, 2nd-, and 3rd
      order transition probabilities. Measures directly assessing awareness of the
      probabilities show that the knowledge is implicit early in training and becomes
      explicit with extended training.

PMID- 11294446
TI  - Causal judgments about relations between multilevel variables.
AB  - Three experiments presented stimulus information about cause and effect variables
      taking 3 quantitative values. Judgments tended to vary in accordance with
      considerations of conditions affecting the validity of causal inference from
      correlational data: whether causal candidates were presented simultaneously or in
      a temporal order such that one could affect the other and whether candidates were
      confounded with each other. The results supported a general hypothesis that
      causal judgments are moderated in accordance with acquired methodological
      intuitions. The fourth experiment showed that tendencies in correlation judgment
      were different from those in causal judgment, further supporting the hypothesis
      that causal judgment from multilevel variable information is, to some extent,
      determined by processes or conceptual frameworks specific to the domain of causal
      cognition.

PMID- 11294447
TI  - Distinguishing common and task-specific processes in word identification: a
      matter of some moment?
AB  - The same 500 words were presented in 6 different word identification tasks
      (Experiment 1: lexical decision, semantic categorization, and 3 speeded naming
      tasks; Experiment 2: delayed naming). Reaction time (RT) distributions were
      estimated for each task and analyses tested for the effects of word frequency and
      animacy on various parameters of the RT distribution. Low frequency words yielded
      more skewed distributions than high frequency words in all tasks except delayed
      naming. The differential skew was most marked for tasks that required lexical
      discrimination. The semantic categorization task yielded highly skewed
      distributions for all words, but the word frequency effect was due to shifts in
      the location of the RT distributions rather than changes in skew. The results are
      used to evaluate the relative contributions of a common lexical access process
      and task-specific processes to performance in lexical discrimination and naming
      tasks.

PMID- 11294448
TI  - Syllables and morphemes: contrasting frequency effects in Spanish.
AB  - Three types of sublexical units were studied in Spanish visual word recognition:
      the syllable, the basic orthographic syllabic structure (BOSS), and the root
      morpheme. In Experiment 1, using a lexical-decision task, a typical inhibitory
      effect of the first-syllable frequency was found (while keeping constant the BOSS
      frequency) as well as the word-frequency effect. Experiment 2 examined the role
      of both the BOSS frequency and the word frequency, also in a lexical-decision
      task. Syllable frequency was controlled. Both the BOSS frequency and the word
      frequency showed facilitatory effects. However, in Experiments 3A and 3B, a
      facilitatory effect of the root frequency (when controlling for BOSS frequency)
      and a null effect of BOSS frequency (when controlling for root frequency) were
      found, suggesting that the BOSS effect is in fact reflecting a morpheme effect. A
      review of the current models shows that it is difficult to integrate syllables
      and morphemes in a unique model.

PMID- 11294449
TI  - Processing ambiguous verbs: evidence from eye movements.
AB  - In 2 eye-tracking experiments, participants read verbs that had 2 (unrelated)
      meanings or 2 (related) senses in contexts that disambiguated before or after the
      verb, to the dominant or subordinate interpretation. A 3rd experiment used
      unambiguous verbs. The results indicated that the language processor used
      information about context in the early stages of resolving meaning ambiguities
      but only during integration for sense ambiguities. Effects of preference were
      delayed for both types of verbs. The results contrast with findings concerning
      the processing of nouns (e.g., K. Rayner & S. A. Duffy, 1986). For meaning
      ambiguities, the authors argue that delays in resolution allow both meanings to
      reach a high level of activation, thus reducing effects of frequency. For sense
      ambiguities, the authors argue that the processor does not access multiple senses
      but activates one underspecified meaning and uses context to home in on the
      appropriate sense.

PMID- 11294450
TI  - Recency in verb phrase attachment.
AB  - Four experiments investigated attachment preferences in constructions involving 3
      verb phrases (VPs) followed by an attaching modifier. Readers preferred
      attachment to the most recent (lowest) VP site overall and preferred to attach
      the modifier to the middle VP over the highest VP, demonstrating a monotonic
      recency-based preference ordering. This pattern could not be attributed to
      lexical or plausibility-based preferences. The results contrast with the pattern
      for relative clause attachment into 3 potential noun phrase sites, where the
      preference ordering is nonmonotonic (e.g., E. Gibson, N. J. Pearlmutter, E.
      Canseco-Gonzalez, & G. Hickok, 1996), and support the multiple-constraint theory
      described by E. Gibson and N. J. Pearlmutter (1998), which proposes that
      recency/locality and a secondary factor, predicate proximity, combine with
      lexical, grammatical, prosodic, and contextual constraints to determine
      attachment preferences.

PMID- 11294451
TI  - The combination of lamotrigine and mild hypothermia prevents ischemia-induced
      increase in hippocampal glutamate.
AB  - The excessive release of glutamate during cerebral ischemia may play an important
      role in subsequent neuronal injury. Both lamotrigine and hypothermia have
      independently been shown to attenuate the release of glutamate. In this study,
      the authors sought to determine whether these effects were additive. Thirty-five
      New Zealand White rabbits were randomized to one of six groups: a normothermic
      control group; a lamotrigine-treated group; two hypothermic groups at 33 degreesC
      or 34.5 degreesC; or two groups treated with both hypothermia at 33 degreesC or
      34.5 degreesC plus lamotrigine. Animals were anesthetized before implanting
      microdialysis probes in the hippocampus. Esophageal temperature was maintained at
      38 degreesC in the control and lamotrigine groups, while the temperatures of
      animals in the hypothermia and hypothermia-plus-lamotrigine groups were cooled to
      33 degreesC or 34.5 degreesC. Two 10 minute periods of global cerebral ischemia
      were produced by inflating a neck tourniquet. Levels of glutamate in the
      microdialysate were then determined using high-performance liquid chromatography.
      Extracellular glutamate concentrations increased only slightly from baseline
      during the first ischemic period. Glutamate levels during the second ischemic
      episode in the hypothermia-plus-lamotrigine group (34.5 degreesC) were
      significantly lower than those in the hypothermia group alone (34.5 degreesC),
      lamotrigine, or control groups (P < .01). The fact that mild hypothermia (34.5
      degreesC) plus lamotrigine (20 mg/kg) together were more effective in inhibiting
      extracellular glutamate accumulation than hypothermia (34.5 degreesC) or
      lamotrigine (20 mg/kg) alone, suggests the potential for increased
      neuroprotection by the addition of lamotrigine to mild hypothermia.

PMID- 11294452
TI  - The effects of sevoflurane and isoflurane on intracranial pressure and cerebral
      perfusion pressure after diffuse brain injury in rats.
AB  - Twenty-four adult male Wistar rats, weighing 220 to 290 g, were anesthetized with
      30 mg/kg intraperitoneal sodium thiopental, then underwent a tracheostomy. After
      diffuse impact-acceleration brain injury (BI) was induced, each rat was paralyzed
      and mechanically ventilated with 30% O2 in nitrous oxide (N2O). The rats were
      assigned randomly to two groups, each of which received one of the two volatile
      anesthetic agents, sevoflurane or isoflurane. The anesthetics were administered
      at 0.5, 0.75, 1.0, and 1.25 minimal alveolar concentration (MAC) for 30 minutes
      each, respectively, and anesthesia was maintained at 0.75 MAC during the last
      hour of the study period. Intracranial pressure (ICP), mean arterial pressure
      (MAP), rectal and intrahemispheric temperatures, and end-tidal volatile
      anesthetic concentrations were monitored continuously throughout the 3 hours,
      with measurements recorded every 15 minutes. At baseline, there were no
      significant differences between the two groups regarding the monitored
      physiologic values. In the sevoflurane group, MAP fell significantly after 45
      minutes, and a similar change was observed in the isoflurane group after 30
      minutes (P < .05, P < .01, and P < .001, respectively). Intracranial pressure
      increased significantly at 45 minutes in the sevoflurane group (P < .01) and
      remained elevated from 60 minutes until the end of the study period (P < .01, P <
      .001). Although ICP increased in the isoflurane group, the change was not
      significant. Cerebral perfusion pressure (CPP) decreased in parallel with MAP,
      with the reduction in the sevoflurane group being more pronounced than that in
      the isoflurane group. The results demonstrated that, under the conditions of
      diffuse BI, animals that were anesthetized with sevoflurane had higher ICP and
      lower CPP levels than those anesthetized with isoflurane.

PMID- 11294453
TI  - Hypertonic-hyperoncotic saline differentially affects healthy and glutamate
      injured primary rat hippocampal neurons and cerebral astrocytes.
AB  - Hypertonic-hyperoncotic saline solutions (HHS) have been used for small-volume
      resuscitation and to treat intracranial hypertension and cerebral edema in
      neurocritical care. Little is known on the response of brain cells to direct
      exposure in HHS, which may occur in blood-brain barrier disruption. We studied
      the effects of HHS on healthy and glutamate-injured brain cells in vitro. To
      model a hypertonic-hyperoncotic environment, rat hippocampal neurons and cerebral
      astrocytes were exposed to hypertonic saline and hydroxyethyl starch (HES) added
      to medium for 15 minutes (final osmolarity: 350 mOsm/L in the neuronal, 373
      mOsm/L in the glial medium; 2.5 mg/mL HES in both media). To simulate
      excitotoxicity, cells were exposed to 100 microM glutamate for 8 minutes before
      exposure to HHS. Cell viability was analyzed by morphology and vital dye
      staining; intracellular water space (WS) and glucose use were measured by
      scintillation spectrometry using 3-O-methyl[14C]-D-glucose and [3H]2-deoxy-D
      glucose ([3H]2-DG). After 24 hours, exposure to HHS added to medium caused a 30%
      reduction in viability of healthy neurons (P < .05), but did not exacerbate the
      glutamate-induced 50% decrease in neuronal survival. One hundred percent
      astrocyte viability remained unchanged. The WS of astrocytes and surviving
      neurons was negligibly altered. Exposure to HHS added to medium caused a 35%
      reduction in [3H]2-DG in healthy and glutamate-injured neurons (P < .05), but did
      not affect [3H]2-DG in astrocytes. Our data show that HHS may potentially injure
      hippocampal neurons. Preserved WS values imply that live cells maintained volume
      regulation capabilities, indicating a lack of dehydration 24 hours after exposure
      to HHS. Impaired glucose use predisposes neurons to disturbed metabolism, which
      may influence neuronal outcome after brain injury.

PMID- 11294454
TI  - Temporal profiles of the levels of endogenous antioxidants after four-vessel
      occlusion in rats.
AB  - Although it is known that development of lipid peroxidation after ischemia occurs
      predominantly in vulnerable regions, temporal profiles of antioxidants after
      ischemia have not been regionally elucidated. After reperfusion periods of 0, 3,
      24, and 72 hours following 20 minutes of four-vessel occlusion (n = 6 in each
      group), the concentration of total glutathione (GSH) and the activities of
      superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) were
      assayed in the hippocampus, parietal cortex, striatum, thalamus, and brain stem.
      The levels of all antioxidants were unchanged in all regions without reperfusion;
      however, the concentration of total GSH significantly decreased in the
      hippocampus at 3 hours after the onset of reperfusion, and showed a maximum
      decrease in the hippocampus (68% of the sham-control level), parietal cortex (78%
      of the sham-control level), and striatum (76% of the sham-control level) after 24
      hours of reperfusion. After 72 hours of reperfusion, these regions and the
      thalamus showed restoration and an increase in the total GSH concentration,
      respectively. The activities of SOD, GSH-Px, and catalase were stable during the
      reperfusion period, but the hippocampus showed significant increases in these
      enzyme activities and the parietal cortex and striatum showed significant
      increases in SOD activities at 72 hours after the onset of reperfusion. These
      results indicate that endogenous antioxidants take 72 hours for restoration in
      vulnerable regions after 20 minutes of four-vessel occlusion in rats.

PMID- 11294455
TI  - Sudden presentation of intracranial meningioma after elective general anesthesia.
AB  - A case of "silent" intracranial meningioma unmasked by narcosis is described. The
      diagnosis was made because of the patient's failure to wake up after elective
      general anesthesia for orthopaedic surgery. Factors leading to this complication
      and its management are discussed. Early computed tomography scan and antiedema
      therapy are strongly suggested for these patients.

PMID- 11294456
TI  - Pseudoarrythmia from evoked potential monitoring.
AB  - Somatosensory Evoked Potentials (SSEP) are used frequently in spinal
      instrumentation cases. In this report, we describe electrocardiographic artifacts
      from SSEP monitoring and offer a new explanation of the etiology.

PMID- 11294457
TI  - Effect of intracarotid papaverine on human cerebral blood flow and vascular
      resistance during acute hemispheric arterial hypotension.
AB  - This study assessed the feasibility of augmenting cerebral blood flow (CBF) and
      decreasing hemispheric cerebrovascular resistance (CVR) by intracarotid
      papaverine during acute cerebral hypotension. Awake patients (n = 10) undergoing
      transfemoral balloon occlusion of an internal carotid artery (ICA) with
      nitroprusside (SNP)-induced systemic hypotension (10% reduction of mean arterial
      pressure) were studied. We measured mean femoral artery pressure (MAP), mean
      distal ICA pressure (P(ica)), and CBF (intracarotid 133Xe) at two time points:
      before and after intracarotid papaverine infusion (1 or 7 mg/min). Two patients
      became symptomatic immediately after ICA occlusion and were excluded. One patient
      developed a focal seizure during papaverine infusion. In another, the occlusion
      balloon deflated prematurely. Of the remaining six patients, two of the three
      patients who received high-dose papaverine (7 mg/min) developed transient
      obtundation. The remaining three patients, who received low-dose papaverine (1
      mg/min), did not develop any neurologic symptoms. There was a trend for
      intracarotid papaverine to increase hemispheric CBF by 36% (33 +/- 10 versus 45
      +/- 22 ml x 100 g(-1) x min(-1), P = .084, n = 6); papaverine decreased CVR from
      1.3 +/- 0.4 to 1.0 +/- 0.3 mm Hg x ml(-1) x 100 g(-1) x min(-1) (P = .049). There
      was no significant change in heart rate, MAP, or P(ica) during experimental
      protocol. Manipulation of CVR by intracarotid papaverine during acute hemispheric
      arterial hypotension appears to be feasible. Further studies are needed to
      establish safety and efficacy.

PMID- 11294458
TI  - Episodic high irrigation pressure during surgical neuroendoscopy may cause
      intermittent intracranial circulatory insufficiency.
AB  - Intermittent high peak pressure values inside the endoscope during
      neuroendoscopic surgical procedures are associated with postoperative morbidity.
      Unexpected delay in awakening is the complication most frequently observed by the
      anesthesiologist as a result of high peak pressure values inside the endoscope.
      During eight neuroendoscopic procedures the authors continuously monitored
      cerebral hemodynamic function, using a transcranial doppler (TCD) probe fixed on
      patients' temporal window. We observed that episodes of high peak pressure values
      inside the endoscope during neuroendoscopic navigation rinsing periods resulted
      in changes in the TCD wave profile consistent with "near intracranial circulatory
      arrestlike" wave. No systemic hemodynamic warning signs accompanied these
      intermittent episodes of severe decrease in cerebral perfusion pressure. When the
      rinsing liquid was allowed to escape, the pressure inside the endoscope decreased
      and the TCD wave immediately returned to its previous value. Neuroendoscopic
      procedures, although classified as minimally invasive surgery, warrant special
      monitoring that could alert us to a decrease in cerebral perfusion pressure.
      Middle cerebral artery TCD recording is a reliable and accurate tool for this
      purpose.

PMID- 11294459
TI  - Anesthesia for magnetic resonance guided neurosurgery: initial experience with a
      new open magnetic resonance imaging system.
AB  - The authors present their initial experience with a compact open magnetic
      resonance (MR) image-guided system, (PoleStar N-10, Odin Medical Technologies,
      Yokneam, Israel) used in a standard operating room, modified for radio frequency
      (RF) shielding. The low intensity of the magnetic field (0.12T), and the ability
      to lower the magnet from the operative field during surgery allows for an almost
      routine surgical procedure, in addition to the benefits of using intraoperative
      MR imaging. Although an MR compatible anesthesia machine and monitoring system
      are used, the system offers anesthesiologists access to the patient at all times
      during the procedure, and the ability to use conventional surgical equipment,
      syringe pumps, and warming devices. Propofol and remifentanil, used for
      maintaining anesthesia, allow early extubation and neurological evaluation at the
      end of surgery. Electrocorticographic monitoring can be used during surgery for
      epilepsy, and awake craniotomy can be performed. More experience with this new
      imaging system is required to assess its influence on clinical decision making
      and outcome.

PMID- 11294460
TI  - Seizures in the adult intensive care unit.
AB  - Seizures are a common occurrence in the intensive care unit (ICU). The
      presentation of seizures is usually as focal or generalized motor convulsions,
      but other seizure types may occur. Etiologies of the seizures are typically
      secondary either to primary neurologic pathology or a consequence of critical
      illness and clinical management. Particularly important as precipitants of
      seizures are hypoxia/ischemia, drug toxicity, and metabolic abnormalities. It is
      important to properly diagnose the seizure type and its cause to ensure
      appropriate therapy. Most seizures occur singly, and recurrence is usually
      prevented with initiation of anticonvulsant therapy. However, status epilepticus
      may develop, which requires emergent treatment before irreversible brain injury
      occurs. Treatment with anticonvulsants is not without untoward risks, however,
      and primary toxicities of these agents is reviewed. After traumatic head injury,
      brain surgery, or cerebrovascular accidents, many patients are at risk for
      seizures. Current data on the benefits of prophylactic therapy for such patients
      is also reviewed.

PMID- 11294461
TI  - Combining median electroencephalography frequency and sympathetic activity in an
      index to evaluate opioid detoxification in patients.
AB  - During rapid opioid detoxification, increased sympathetic activity and a greater
      median frequency (MF) of activity on electroencephalography (EEG) have been
      reported. The purpose of this study was to evaluate a new index for
      detoxification that combines sympathetic activity and MF data. After informed
      consent was obtained, eight patients were sedated with propofol. The MF of EEG
      activity derived from frontal electrodes was determined. Heart rate variability
      was evaluated in 256-second segments by power spectral analysis, and sympathetic
      activity was determined by the low frequency component. The Hoffman Index for
      narcotic detoxification was weighted 70% to sympathetic activity and 30% to MF to
      normalize the difference in scales and to provide adequate weight to the
      sympathetic component. Opioid detoxification was produced by infusion of 25 mg
      naloxone for 30 minutes, followed by a 24-hour infusion of 1 mg per hour. The MF
      showed a rapid increase during high-dose infusion of naloxone, but the peak
      response occurred 1 to 2 hours later. Sympathetic activation and the Hoffman
      Index increased more slowly after the start of naloxone infusion, but peak
      increases in all components occurred at approximately the same time. The peak
      increases in Hoffman Index (110% of baseline), MF (260%), and sympathetic
      activity (304%) during administration of naloxone were significant and correlated
      with respect to time (r = 0.89-0.94). The Hoffman Index showed an early increase
      related to MF and a well-defined peak response indicative of sympathetic and MF
      activity. The behavior of the Hoffman Index in relation to the MF and sympathetic
      activity more clearly indicated the onset of opioid detoxification and the
      maximum response to opioid reversal than did MF or sympathetic activity alone.

PMID- 11294462
TI  - Rocuronium-induced neuromuscular blockade is affected by chronic phenytoin
      therapy.
AB  - Patients receiving chronic anticonvulsant therapy have been reported to show
      resistance to certain nondepolarizing neuromuscular blockers. In this study, the
      effects of chronic phenytoin therapy on the onset, duration, and recovery of
      rocuronium action was assessed. Thirty-six patients scheduled for various
      neurosurgical procedures were studied: 18 receiving chronic phenytoin therapy
      (Group I) and 18 controls (Group II). Rocuronium 0.6 mg/kg (2 x DE95) was
      administered after induction of general anesthesia with 4-6 mg/kg thiopental
      sodium and 3-5 microg/kg intravenous (IV) fentanyl. Maintenance anesthesia
      consisted of N2O in O2, 0.5% end-tidal isoflurane, and a fentanyl infusion.
      Neuromuscular block was monitored with acceleromyography of the adductor pollicis
      brevis muscle by using a TOF-GUARD Biometer monitor (Biometer International A/S,
      Odense, Denmark). According to the amplitude of the first response of train-of
      four, neither the lag time nor the onset time differed between the two groups.
      However, the recovery index was significantly shorter in patients chronically
      treated with phenytoin (mean recovery index: control group, 8.3 +/- 1.7 minutes;
      phenytoin group, 6.7 +/- 2.3 minutes; P < .05). In addition, the times of
      recovery to 10%, 25%, 75%, and 90% of the baseline response were also
      significantly shorter in the phenytoin group than in the control group. We
      conclude that the duration of action of rocuronium and the recovery index were
      affected by chronic phenytoin therapy.

PMID- 11294463
TI  - Impact of a neuroscience intensive care unit on neurosurgical patient outcomes
      and cost of care: evidence-based support for an intensivist-directed specialty
      ICU model of care.
AB  - Analysis of patient data from a new neuroscience intensive care unit (NSICU)
      permitted evaluation of whether such a specialty ICU favorably altered clinical
      outcomes in critically ill neuroscience patients, and whether such a care model
      produced an efficient use of resources. A retrospective review was performed to
      compare (1) the clinical outcomes, as defined by percent mortality and
      disposition at discharge, between patients with a primary diagnosis of
      intracerebral hemorrhage treated in 1995 in medical or surgical ICUs and those
      treated in the same medical facility in an NSICU in 1997; and (2) the efficiency
      of care, as defined by length of ICU stay, total cost of care, and specific
      resource use, between patients treated in the NSICU and national benchmark
      standards for general ICUs during the 1997 fiscal year (FY). In the latter,
      extracted patient population data on neurosurgery patients requiring ICU
      treatment during FY 1997 were used with the following adjacent-disease related
      group (A-DRG)-coded diseases: craniotomy with and without coma or intracerebral
      hemorrhage, and skull fracture with and without coma lasting longer than 1 hour.
      Outcome measures of percent mortality and disposition at discharge in patients
      with intracerebral hemorrhage were significantly improved (P < .05), compared
      with those in a similar cohort treated 2 years earlier in a general ICU setting.
      Also, patients treated in the NSICU had shorter hospital stays (P < .01 ) and
      lower total costs of care (P < .01) than a national benchmark. The data suggest
      that a neuroscience specialty ICU arena staffed by specialty-trained intensivists
      and nurses is beneficial.

PMID- 11294464
TI  - Propofol [correction of propfol] versus methohexital for electroconvulsive
      therapy: a meta-analysis.
AB  - A systematic search (Medline, Cochrane library, Embase, bibliographies, to
      5.2000, no language restriction) was performed for published reports of
      randomized comparisons of propofol and methohexital for anesthesia during
      electroconvulsive therapy. We analyzed 15 trials with data on 706 patients. The
      duration of motor seizure was shorter with propofol (range, 18-39 seconds) than
      with methohexital (range, 26-48 seconds, weighted mean difference 8.4 seconds
      [95% CI, 6.6-10.0]). With both propofol and methohexital, there was little
      evidence of an association between dose and duration of motor seizure (for
      propofol: r2 = 0.25, P = .08; for methohexital: r2 = 0.11, P = .27). Two small
      trials investigated clinical outcome; results were inconclusive. Data on adverse
      effects were sparse. Duration of seizure was not proven to be a useful measure of
      treatment success in the study of electroconvulsive therapy with propofol or
      methohexital. The impact of the technique of anesthesia on the underlying disease
      needs to be established.

PMID- 11294465
TI  - Local anesthetics potentiate nitric oxide synthase type 2 expression in rat glial
      cells.
AB  - Expression of the calcium-independent nitric oxide synthase (NOS2) contributes to
      damage in neurologic disease and trauma. The effects of local anesthetics on NOS2
      expression have not been examined. The authors tested the effects of four local
      anesthetics on the expression of NOS2 in immunostimulated rat C6 glioma cells.
      Incubation with local anesthetics alone did not induce nitrite accumulation;
      however, the nitrite production induced by stimulation with bacterial endotoxin
      lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was increased in a dose
      dependent manner by bupivacaine (maximal 3-fold at 360 microM), tetracaine
      (maximal 7-fold at 360 microM), and lidocaine at higher doses (5-fold increase at
      3.3 mM). Significant increases in nitrite production were observed in
      concentrations of bupivacaine or tetracaine as low as 120 microM, which
      correspond to 30 microg/mL (.003% weight/volume). In contrast, ropivacaine had
      little effect on nitrite production (160% of control values) and only at the
      highest concentration (3.3 mM, corresponding to 890 microg/mL or 0.089% w/v)
      tested. Increased nitrite production was not caused by cytotoxic effects of the
      drugs used, as assessed by release of intracellular lactate dehydrogenase.
      Increased nitrite production was accompanied by increased NOS2 catalytic
      activity, steady state mRNA levels, and promoter activation. These results
      demonstrate that submillimolar doses of two commonly used local anesthetics can
      increase glial NOS2 expression.

PMID- 11294466
TI  - A coculture model of intrahepatic islet transplantation: activation of Kupffer
      cells by islets and acinar tissue.
AB  - Clinical and experimental studies of intrahepatic islet transplantation have
      allowed histological and systemic observations to be made, but the location of
      the transplanted islets makes it difficult to assess direct effects on the cells
      of the liver. An in vitro coculture model of Kupffer cells with islets or
      pancreatic acinar tissue is described, using porcine tissue and measuring the
      secretion of thromboxane B2, prostaglandin E2, 6-keto-prostaglandin F1alpha, and
      prostaglandin F2alpha as an indicator of Kupffer cell stimulation. The results
      have demonstrated activation of Kupffer cells in the presence of acinar or islet
      tissue, both when the cells were in direct contact and when separated by a
      membrane. This indicated that the stimulation was due to a soluble factor or
      factors, and was confirmed by the culture of Kupffer cells with acinar
      conditioned medium. The degree of stimulation was much greater with acinar tissue
      than with islets. In subsequent experiments, aprotinin, an enzyme activation
      inhibitor, was added to the cocultures in an attempt to reduce Kupffer cell
      activation. This had no effect, possibly due to the fact that the endogenous
      pancreatic enzymes may already be activated during digestion of the pancreas.
      Aprotinin alone caused an increase in secretion of eicosanoids from Kupffer
      cells. The high response to acinar tissue is of particular relevance to islet
      autotransplantation in which unpurified pancreatic digest is often transplanted.
      The clinical effectiveness of aprotinin in the light of these results is
      discussed. In conclusion, although unable to mimic the complex situation
      following intrahepatic islet transplantation, the coculture model described here
      allows the opportunity to assess the events relating to specific cell types, and
      will provide the scope to undertake more detailed studies on the mechanisms
      involved. The same model could be applied to the coculture of pancreatic tissue
      with hepatocytes to determine any effects on the normal function of hepatocytes.

PMID- 11294467
TI  - Human pancreatic ductal cells: large-scale isolation and expansion.
AB  - The in vitro differentiation of pancreatic stem cells has recently been shown to
      represent a new source of beta cells for cell therapy in diabetes. Human ductal
      cell differentiation, in vitro, has been documented in three-dimensional (3D)
      culture and recently substantiated. Although encouraging, the optimization of the
      ductal cell source, expansion and differentiation ex vivo are mandatory for
      clinical relevance. We compared three sources of human ductal cells (hDC) (method
      A1-2, B, and C). The classical main duct isolation of hDC by explant (A1), or
      enzymatic digestion (A2), was compared with two indirect methods: from 3D
      cultured human islet/duct-enriched fractions (B) and dedifferentiated exocrine
      fractions (C). Method A: few viable hDC were obtained from the main duct. Method
      B: embedding islet/duct rich fraction in 3D collagen gels expands the cytokeratin
      19 (CK19)-positive ductal component in the form of ductal cysts, as we described
      previously; monolayers derived from digested cysts were 80% ductal (CK19). Method
      C: initially adherent amylase-positive exocrine clusters contained 12% (CK19) to
      22% (CK7) ductal cells. One-week exocrine cultures were amylase negative and 46%
      (CK19) to 63% (CK7) ductal. Cell viability varied: <20% (A1), 81+/-12% (B), 91+/
      2% (C). Extrapolating total yields we obtained (+/-SEM): 10.5+/-4.6 x 10(3) (A1),
      36+/-18 x 10(3) (A2), 292+/-50 x 10(6) (B), 1696+/-526 x 10(6) (C) viable hDC per
      pancreas. A secondary monolayer expansion of cyst-derived hDC (method B) was
      achieved with NuSerum (4.2-fold on plastic, 2.6-fold on 804G matrix; p < 0.05 vs.
      control cells on plastic). First passage exocrine-derived ductal cells also
      responded to matrix and to growth factors, albeit not significantly. In
      conclusion, this study demonstrated that an abundant hDC supply can be obtained
      from islet/duct or exocrine fractions followed by monolayer expansion with
      NuSerum. If their differentiation capacity is confirmed, in particular exocrine
      derived ductal cells may represent a promising abundant source of islets for
      allogenic and autologous diabetes cell therapy.

PMID- 11294468
TI  - Neural xenotransplantation: pretreatment of porcine embryonic nigral tissue with
      anti-Gal antibodies and complement is not toxic for the dopaminergic neurons.
AB  - The immunogenicity of porcine tissue is a major obstacle to its use as donor
      material in xenotransplantation for neurodegenerative diseases. We are currently
      evaluating a novel strategy for reducing the immunogenicity, in which the alpha
      galactosyl epitope (Galalpha1,3Galbeta1,4GlcNAc-R) is used as a target for
      antibody- and complement-mediated removal of microglia. In the present study, our
      aim was to determine whether a pretreatment with antibodies against the alpha
      galactosyl epitope (anti-Gal) and complement would lyse or otherwise damage
      dopaminergic neurons in porcine embryonic ventral mesencephalon (VM), the donor
      tissue for treatment of Parkinson's disease by xenotransplantation. Cell
      suspensions prepared from VM tissue from 27-day-old pig embryos were incubated
      with anti-Gal, purified from normal human serum by affinity chromatography, or
      medium only (control), and subsequently with rabbit complement. After these
      pretreatments, the cell suspensions were transplanted into the right striatum of
      14 adult rats (two groups of 7 animals). The animals were sacrificed 20 days
      after transplantation, the brains were processed for histology, and the sections
      were stained for Nissl substance, porcine neurofilament, tyrosine hydroxylase,
      and rat CD45 to determine graft volume, presence of porcine neurons, content of
      dopaminergic cells, and leukocyte infiltration, respectively. The VM tissue
      pretreated with anti-Gal and complement gave rise to dopaminergic grafts that
      were indistinguishable from those derived from VM tissue given the control
      pretreatment. In 5 of the 14 animals, the grafts were infiltrated by host
      leukocytes, but in two of these recipients, the infiltration was only minimal. We
      conclude that anti-Gal and complement can be applied to porcine embryonic VM
      tissue without damaging the dopaminergic neurons and their precursors.

PMID- 11294470
TI  - Adult bone marrow transplantation after stroke in adult rats.
AB  - We transplanted adult whole bone marrow prelabeled with bromodeoxyuridine (BrdU)
      into the ischemic boundary zone of the adult rat brain at 1 day after 2 h of
      middle cerebral artery occlusion (MCAo). Approximately 3.3% of 10(6) transplanted
      bone marrow cells were BrdU reactive at 14 days after MCAo. BrdU-reactive cells
      expressed neuronal and astrocytic proteins, neuronal nuclei protein (NeuN, 1%),
      and glial fibrillary acidic protein (GFAP, 5%) immunoreactivities, respectively.
      In addition, bone marrow transplantation promoted proliferation of ependymal and
      subependymal cells, identified by nestin (a neuroepithelial stem cell marker),
      within the ventricular zone and subventricular zone (VZ/SVZ). These data suggest
      that intracerebral transplantation of bone marrow could potentially be used to
      induce plasticity in ischemic brain.

PMID- 11294469
TI  - Update on immunoisolation cell therapy for CNS diseases.
AB  - Delivery of potentially therapeutic drugs to the brain is hindered by the blood
      brain barrier (BBB), which restricts the diffusion of drugs from the vasculature
      to the brain parenchyma. One means of overcoming the BBB is with cellular
      implants that produce and deliver therapeutic molecules. Polymer encapsulation,
      or immunoisolation, provides a means of overcoming the BBB to deliver therapeutic
      molecules directly into the CNS region of interest. Immunoisolation is based on
      the observation that xenogeneic cells can be protected from host rejection by
      encapsulating, or surrounding, them within an immunoisolatory, semipermeable
      membrane. Cells can be enclosed within a selective, semipermeable membrane
      barrier that admits oxygen and required nutrients and releases bioactive cell
      secretions, but restricts passage of larger cytotoxic agents from the host immune
      defense system. The selective membrane eliminates the need for chronic
      immunosuppression of the host and allows the implanted cells to be obtained from
      nonhuman sources. In this review, cell immunoisolation for treating CNS diseases
      is updated from considerations of device configurations, membrane manufacturing
      and characterization in preclinical models of Alzheimer's and Huntington's
      disease.

PMID- 11294471
TI  - Prolonged postlesion transplantation delay adversely influences survival of both
      homotopic and heterotopic fetal hippocampal cell grafts in Kainate-lesioned CA3
      region of adult hippocampus.
AB  - Fetal hippocampal CA3 cell grafts exhibit dramatically enhanced survival when
      transplanted at an early postlesion delay of 4 days into the lesioned CA3 region
      of adult hippocampus. However, survival of these homotopic grafts following
      placement at late postlesion time points when the host milieu is considerably
      less receptive to grafts is unknown. We hypothesize that an extended postlesion
      delay at the time of grafting will lead to significant diminution in cell
      survival of both homotopic and heterotopic fetal transplants grafted to lesioned
      adult CNS. We quantitatively investigated absolute cell survival of 5'
      bromodeoxyuridine-labeled fetal hippocampal CA3 and CA1 cell grafts, following
      transplantation into the lesioned CA3 region of adult rat hippocampus, at a delay
      of 45 days after a unilateral intracerebroventricular administration of kainic
      acid (KA). Survival of these grafts was also analyzed in intact CA3 of the
      hippocampus contralateral to KA administration for comparison. In lesioned CA3
      region, CA3 (homotopic) and CA1 (heterotopic) grafts exhibited comparable but
      only moderate survival, with a recovery of only 21-31% of injected cells. Cell
      survival in these grafts into lesioned hippocampus was similar to survival of
      grafts placed into the contralateral intact CA3 region. These results are in
      sharp contrast to increased graft survival measured following transplants
      performed at 4 days postlesion. In such grafts placed early, there was both a
      significantly higher cell survival than grafts placed into the intact CA3 region
      and also a characteristic differential survival based on graft cell specificity
      to the lesioned CA3 region (Zaman et al., Exp. Neurol., 161:535-561, 2000). Thus,
      the enhanced conduciveness of lesioned CA3 region for survival of homotopic CA3
      cell grafts observed at 4 days postlesion wanes by 45 days postlesion to that of
      intact CA3 region, in spite of residual loss of CA3 neurons with the lesion.
      Strategies that considerably augment graft cell survival may therefore be
      critical for optimal integration of fetal grafts into the adult CNS at late
      postlesion time points.

PMID- 11294472
TI  - Delta opioid peptide augments functional effects and intrastriatal graft survival
      of rat fetal ventral mesencephalic cells.
AB  - Delta enkephalin analogue [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been shown to
      protect dopamine transporters from methamphetamine-induced neurotoxicity. In the
      present study, we demonstrate that exposure of embryonic ventral mesencephalic
      cells to DADLE (0.01 g/ml), prior to intrastriatal transplantation, enhanced
      functional recovery and graft survival in 6-hydroxydopamine-induced
      hemiparkinsonian rats. At 6 and 8 weeks posttransplantation, animals that
      received DADLE-treated cell grafts exhibited significantly higher (near normal)
      spontaneous locomotor behaviors, as well as trends of greater reversal of motor
      asymmetrical behaviors compared with animals that received nontreated cell
      grafts. Histological examination revealed that animals transplanted with DADLE
      treated cell grafts exhibited about twice the number of surviving tyrosine
      hydroxylase-immunoreactive grafted neurons compared with those animals that
      received nontreated cell grafts. These results suggest that DADLE should be
      considered as an adjunctive agent for neural transplantation therapy in
      Parkinson's disease.

PMID- 11294473
TI  - Apoptosis occurs in isolated and banked primary mouse hepatocytes.
AB  - Isolation and cryopreservation of freshly isolated hepatocytes is considered a
      standard procedure for the long-term storage of liver cells. However, most
      existing methods for banking hepatocytes do not allow sufficient recovery of
      viable cells to meet the needs of basic research or clinical trials of hepatocyte
      transplantation. The mechanisms underlying this poor rate of hepatocyte recovery
      are unknown. Although much of the cellular damage in freezing is caused by
      formation of ice crystals within the cells, this is largely prevented by the use
      of dimethyl sulfoxide (DMSO) and controlled rate freezing. As we demonstrated
      recently, necrosis does occur in primary hepatocytes following isolation and
      cryopreservation. In the present study, we explored the contribution of
      apoptosis, another form of cell death, in primary hepatocytes banked for
      transplantation. We evaluated apoptosis of C57BL/6J mouse primary hepatocytes
      using several different methods. Annexin binding and the TUNEL assay, in
      conjunction with flow cytometry and confocal laser scanning microscopy, revealed
      that the percentage of apoptotic cells was dramatically elevated in cryopreserved
      cells compared with that in the control group of unfrozen cells. DNA laddering
      detected by DNA electrophoresis in agarose gel also supported the presence of
      apoptosis in isolated and banked liver cells. Moreover, we found that the
      addition of glucose (from 10 to 20 mM) into the freezing solution (University of
      Wisconsin Solution) decreased the rate of apoptosis by 84% and improved the cell
      attachment at least fourfold in cryopreserved cells. These results suggest that
      apoptosis might contribute to cell death in isolated and banked primary
      hepatocytes.

PMID- 11294474
TI  - Engraftment and albumin production of intrasplenically transplanted rat
      hepatocytes (Sprague-Dawley), freshly isolated versus cryopreserved, into Nagase
      analbuminemic rats (NAR).
AB  - Banking of cryopreserved hepatocytes is a prerequisite for large-scale hepatocyte
      transplantation in the clinic. We compared the efficacy of intrasplenic
      transplantation into Nagase analbuminemic rats (NAR) of freshly isolated (FIH)
      and cryopreserved (CH) hepatocytes. Hepatocytes were cryopreserved using a
      controlled rate freezing protocol. Albumin production of thawed CH and FIH was
      measured in vitro in culture by ELISA and by Western blot. After in vivo
      intrasplenic transplantation of NAR with either FIH or CH we assessed 1) albumin
      in the serum of recipients by ELISA and by Western blotting analysis at different
      time intervals, and 2) hepatocyte engraftment by albumin immunohistochemical
      staining into spleens and livers at euthanasia. In vitro, albumin was produced up
      to day 4 of culture in both CH and FIH. In vivo, no intrasplenic engraftment of
      hepatocytes occurred. Intrahepatic engraftment of CH (cell number/mm2) was
      significantly (twofold) lower than that of FIH and appeared only as isolated
      cells and small (<10 cells) clusters, while bigger clusters (>10 cells) were
      observed with FIH. In the FIH group, serum albumin production was observed up to
      32-49 days posttransplantation while in the CH group no serum albumin production
      was detected. Our results emphasize the need to improve 1) hepatocyte
      transplantation procedures either by repeated hepatocytes injections and/or by
      transplantation under a regeneration response, and 2) the freeze/thaw protocols
      of hepatocytes.

PMID- 11294476
TI  - A "real time" PCR assay to detect transplanted human liver cells in RAG-1-/-
      mice.
AB  - Xenotransplantation of human liver cells is an expanding field in need of new and
      precise quantitative techniques. "Real time" PCR is a sensitive and accurate
      method of quantifying picogram quantities of DNA. We used "real time" PCR with
      primers complementary to the human alpha-1-antitrypsin gene to assess the
      efficiency of engraftment of human liver cells transplanted into immunotolerant
      RAG-1-/- mice. Standard curves were created by mixing known proportions of human
      and mouse cells. There was a linear relationship between the PCR cycle at which
      DNA was amplified [threshold cycle (C(T)] and the percent human cells (linear
      regression, p < 0.00009). Results were reliable, with a maximum 1.27-fold
      variation in the slopes of repeated standard curves. Linearity was maintained
      from 100% to as low as 0.01%. Therefore, 1 in 10,000 mouse cells could be
      detected in a 100 ng DNA sample. We measured the percent engraftment of human
      liver cells transplanted into the spleen of RAG-1-/- mice. By "real time" PCR
      assay, 0.23% human cells could be detected at 1 day after human cell
      transplantation. These results show that "real time" PCR assay is highly
      sensitive, reproducible, and accurate for detecting human cells in
      xenotransplanted mice.

PMID- 11294475
TI  - Expansion of hepatic and hematopoietic stem cells utilizing mouse embryonic liver
      explants.
AB  - Ex vivo embryonic liver explant culture is a novel and attractive approach to
      obtain abundant hepatic and hematopoietic stem cells. Gene therapy of autologous
      hepatic and hematopoietic stem cells represents an alternative therapeutic
      approach to liver transplantation for genetic and metabolic disorders. In this
      study we characterize the growth and differentiation of hepatic stem cells
      utilizing embryonic liver cultures. Day 9.5 liver buds are microdissected and
      cultured under specific conditions. Modulation of growth conditions by addition
      of hepatocyte growth factor, Flt-3 ligand, and stem cell factor leads to
      enrichment of hepatic progenitor cells in embryonic liver explants. Under these
      conditions, we also demonstrate the role of a novel marker PRAJA-1 to identify
      hepatic stem cells and transitional hepatocytes. Utilization of dexamethasone
      enhanced pseudolobule formation with increased hepatocytic and biliary
      differentiation. Transforming growth factor-beta leads to enrichment of biliary
      cells in the culture. Gut formation is enhanced in the presence of interleukin-3
      and blood formation by increasing the mesodermal tissue in these cultures. We
      also show increased retroviral-mediated expression of the green fluorescent
      protein expression in the expanded hepatic and hematopoietic stem cells under
      different culture conditions. Thus, the embryonic liver explant culture is an
      attractive source for hepatic progenitors and is a possible step towards
      generating nontumorigenic immortalized hepatocytes with possible transplantation
      applications.

PMID- 11294477
TI  - The visual backward masking deficit in schizophrenia.
AB  - 1. Subjects with schizophrenia have an impairment very early in visual
      information processing, requiring a longer minimal stimulus duration than normal
      controls to identify a target stimulus. Subjects with schizophrenia have a
      deficit in visual backward masking, identifying fewer target stimuli than normal
      controls when the target is briefly obscured by a second visual stimulus When
      interstimulus interval is increased parametrically, subjects with schizophrenia
      have trouble identifying target stimuli at intervals that do not affect the
      performance of normal controls. 2. The visual backward masking deficit: is trait
      related; is associated with negative symptoms but has also been associated with
      measures of thought disorder; may or may not be related to treatment with
      neuroleptic medication or other neurocognitive deficits of schizophrenia; is of
      unclear etiology, though researchers have speculated that it involves
      magnocellular channels and/or the cortical dorsal visual processing stream; has
      been shown to be heritable in one study. 3. If visual information processing
      deficits are observed in the unaffected siblings of schizophrenic patients, it
      may be a candidate intermediate phenotype.

PMID- 11294478
TI  - Effects of short and long-term lithium treatment on serum prolactin levels in
      patients with bipolar affective disorder.
AB  - 1. In this study, the authors sought to test the hypothesis that Li (lithium)
      treatment can induce alterations in PRL (prolactin) secretion in euthymic bipolar
      patients compared to controls and that short and long-term administration can
      lead to prolactin changes different from each other. 2. Twenty euthymic bipolar
      male patients on long-term lithium carbonate treatment for more than 6 months and
      15 euthymic male bipolar patients on short-term Li treatment for shorter than 6
      months who met DSM-IV criteria for bipolar affective disorder were included in
      the study. Seventeen age-matched healthy control males were chosen among the
      hospital staff. The mean +/- SD duration of Li use was 68.93+/-46.31 months in
      the long-term lithium-treated group and 4+/-3.42 months in the short-term lithium
      treated group. 3. Serum PRL values in the long-term Li-treated group were
      significantly lower than those of the control group, while there was no
      significant difference in PRL values between the short-term Li-treated group and
      the control group. 4. Our study documents that short-term (<6 months) Li
      treatment does not induce any significant changes in PRL release in bipolar
      patients compared to normal control subjects while long-term Li treatment (>6
      months) leads to lower PRL release compared to the controls. Furthermore, PRL has
      wide intra-interindividual and circadian variations Li-PRL relationship seems to
      be very complex and probably depends on various interactions among dopamine,
      serotonin and PRL. Therefore, further studies are needed to confirm the data.

PMID- 11294479
TI  - The changes of biological markers and treatment efficacy in schizophrenia.
AB  - 1. In a group of schizophrenic patients, the effect and selected parameters of
      biological markers were evaluated during the index hospitalisation in the acute
      phase of schizophrenia (n = 30) and then after one year of ambulatory treatment.
      2. During the acute treatment, a significant drop in symptomatology was recorded
      in average; an analogical tendency was observed further on, too. Apart from that,
      a significant change was observed in 5/41 parameters being monitored (the pair t
      test): I) decrease in the total NES score, II) decrease in the sensorial
      integration subscale NES score, III) increase in psychomotor speed, IV) decrease
      in auditory reaction time, V) increase in basal cortisol. 3. In the comparison of
      the successfully (severity of illness after one year = 1, 2) and unsuccessfully
      (severity of illness after one year > or =3) treated patients in the beginning of
      treatment in the acute phase, the unsuccessful group had a significantly higher
      score of negative symptomatology, and by the end of the acute treatment, again, a
      significantly higher score of negative symptomatology, a higher total PANSS score
      and a greater severity of illness. 4. In the acute phase, the successful group
      had a significantly better score in individual items of the Contemporary Memory
      Scale and a significantly worse performance and goal-aimed concentration in the
      Bourdon test than the unsuccessfully treated one; apart from that, it had a
      significantly higher cortisol level after dexamethasone, which was also reflected
      in the lower percentage rate of dexamethasone nonsupression. 5. In the course of
      the year, a drop in the total NES score for the individual subscales occurred; a
      significant drop was observed in the sensory integration subscale. The worse
      concentration items improved significantly in the successful group in contrast to
      the unsuccessful group, where they showed a downgrade tendency. Changes in
      Contemporary Memory Scale were negligible and mostly below statistical
      significance. Apart from that, a drop in basal cortisolemia occurred in the
      successful group and an increase in cortisolemia after administering
      dexamethasone was registered in the unsuccessful group. 6. The more successful
      group had a significantly lower NES score, a significantly better visual reaction
      time and a smaller forgetting item (in percentiles) after the one-year period.

PMID- 11294480
TI  - Predictors of treatment response in patients with posttraumatic stress disorder.
AB  - 1. This study examines the relation between baseline clinical characteristics in
      patients with posttraumatic stress disorder (PTSD) and response to treatment with
      a reversible monoamine oxidase A inhibitor (RIMA), brofaromine. 2. Data from two
      comparable, double-blind, placebo-controlled studies of brofaromine in patients
      with PTSD were combined. Bivariate analyses of variables of interest and outcome
      were performed. 3. Treatment response was significantly associated with lower
      baseline scores on the full scale Clinician-Administered PTSD Scale (CAPS) and on
      CAPS subscales B (re-experiencing) and C (avoidance/numbing), as well as to drug
      treatment with brofaromine. Placebo response was related to a history of past
      sexual trauma. 4. Brofaromine may have therapeutic benefit in treating PTSD, with
      lower baseline levels of reexperiencing and avoidance/numbing and overall less
      severe PTSD most predictive of outcome.

PMID- 11294481
TI  - Clinical and treatment response characteristics of late-life depression
      associated with vascular disease: a pooled analysis of two multicenter trials
      with sertraline.
AB  - 1. The safety and efficacy of sertraline in the treatment of moderate-to-severe
      major depression in elderly outpatients, aged 60 years and older, with comorbid
      vascular disease was evaluated. 2. An analysis of the pooled results for the
      sertraline treatment group drawn from two prospective, randomized, double-blind
      studies (sertraline vs. fluoxetine, and sertraline vs. nortriptyline) was done.
      Patients were retrospectively categorized into one of 3 clinical groups: 1)
      patients with a current diagnosis of hypertension but no other past or present
      cardiovascular illness (HTN), 2) patients reporting a current or past history of
      cardiovascular illness, but excluding hypertension (VASC), and 3) patients with
      no hypertension, and no other comorbid vascular illness (NoVASC). Patients
      received 12-3. weeks of double-blind treatment with sertraline in flexible daily
      doses in the range of 50 - 150 mg (in the nortriptyline comparator trial) or 50 -
      100 mg (in the fluoxetine comparator trial). 4. Sertraline treatment yielded
      comparable levels of response in all 3 groups (response criterion: CGI-much or
      very much improved) at treatment endpoint on both a completer analysis (HTN, 86%;
      VASC, 89%; NoVASC, 77%) and significantly higher response rates on a 12-week
      endpoint analysis (HTN, 74%; VASC, 69%; NoVASC, 58%; p < 0.05). Sertraline
      treatment was well-tolerated, with no between-group differences in rates of
      adverse events, or in discontinuation due to adverse events. Patients taking 5 or
      more concomitant medications showed no difference, when compared with patients
      taking none-or-one concomitant medication, either in rates of adverse events, or
      in discontinuation due to adverse events. 5. Sertraline was found to be a safe,
      well-tolerated, and effective as an antidepressant in elderly patients suffering
      from hypertension and other forms of vascular comorbidity.

PMID- 11294482
TI  - Health care utilization in patients with schizophrenia maintained on atypical
      versus conventional antipsychotics.
AB  - 1. Patients with schizophrenia who had been stabilized on their antipsychotic
      medication and subsequently maintained on it for a period of at least 18 months
      were identified: clozapine (N=15); risperidone (N=15); depot conventional (N=18);
      oral conventional (N=18). 2. Groups were compared on a clinical measure as well
      as the use of various health care services: hospitalizations; days in hospital,
      emergency room visits; physician and non-physician visits. 3. No differences
      between groups were found for hospitalizations, days in hospital, or emergency
      room visits, while physician and non-physician visits were highest in the
      clozapine group, in keeping with the need for routine hematologic monitoring in
      this population. The clozapine group had the highest baseline clinical scores and
      greatest number of previous hospitalizations. These treatment groups may reflect
      different clinical populations. However, the findings suggest that in drawing
      conclusions regarding long-term benefits of different agents, clinical or
      economic, it would prove useful to include in the evaluation a comparison of
      patients who have been stabilized on each of the treatments.

PMID- 11294483
TI  - Some behavioural effects of antidepressant drugs are time-dependent.
AB  - 1. The effects of repeated administration of antidepressant drugs (imipramine,
      IMI and citalopram, CIT) on the beta- and alpha2-adrenergic as well as
      dopaminergic D3 receptors were compared with time-dependent changes in the
      receptor responsiveness after acute treatment. 2. Repeated treatment with IMI or
      CIT (administered at a dose of 10 mg/kg p.o. twice a day for 14 days) induced
      down-regulation of beta-adrenergic receptors, demonstrated by behavioural
      experiment using salbutamol-induced hypoactivity and by binding studies using
      [3H]CGP12177. The changes in alpha2-adrenergic receptors were studied using
      clonidine-induced hypoactivity, which was attenuated by repeated treatment with
      IMI or CIT. Behavioural responsiveness of dopamine D3 receptors was investigated
      using two doses of 7-OH-DPAT. This drug at a dose of 0.05 mg/kg s.c. induced
      locomotor hypoactivity (interpreted as a result of stimulation of presynaptic
      dopamine D3 receptors), which was reversed by repeated administration of IMI or
      CIT, while 7-OH-DPAT at a dose of 3 mg/kg s.c. (which stimulated postsynaptic
      dopamine D3 receptors) induced significant hyperactivity, which was markedly
      enhanced by repeated administration of antidepressant drugs. 3. The effect of
      acute administration of IMI or CIT measured 14 days after drug treatment were
      similar to the described above alterations at the level of alpha2 adrenoreceptors
      and presynaptic dopamine D3 receptors, i.e. the drugs attenuated clonidine
      induced hypoactivity and reversed locomotor hypoactivity evoked by low dose of 7
      OH-DPAT. To induce the down-regulation of beta-adrenergic receptors or up
      regulation of the behavioural responsiveness of dopaminergic D3 postsynaptic
      receptors, the repeated administration of IMI or CIT was necessary. 4. Therefore
      it has been concluded that presynaptic dopaminergic D3 and alpha2-adrenergic
      receptors are more sensitive to the acute treatment with antidepressant drugs
      than postsynaptic D3 and beta-adrenergic receptors.

PMID- 11294484
TI  - Effect of acute lipopolysaccharide administration on (+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2 aminopropane-induced wet dog shake behavior in rats: comparison
      with body weight change and locomotor activity.
AB  - 1. Several reports have shown that serotonin (5-HT)2A receptor density and its
      function are altered after physiological or pharmacological stress. To examine
      whether an acute administration of lipopolysaccharide (LPS), a bacterial
      endotoxin, affected 5-HT2A receptor function, wet dog shakes of male Wistar rats
      were observed after a subcutaneous injection of DOI, a 5-HT2A receptor agonist
      following LPS treatment. Body weight change and locomotor activity were also
      observed. 2. DOI (1 mg/kg)-induced WDS significantly decreased after 400 or 1000
      microg/kg LPS treatment compared with that of control rats 1 and 3 hr after
      injection, and WDS completely recovered 8 hr after LPS treatment. Treatment with
      10 mg/kg indomethacin (IND) or 1 mg/kg naltrexone (NLTX) canceled the effect of
      400 microg/kg LPS on DOI-induced WDS. 3. Body weight decrease was significantly
      greater in LPS-treated rats compared with control rats 3, 5 and 8 hr after
      treatment. Treatment with IND (10 mg/kg) significantly recovered the reduction in
      body weight induced by 400 microg/kg LPS. Treatment with NLTX (1 mg/kg) also
      prevented the LPS effect on body weight decrease. 4. Eight hr after treatment
      with LPS (400 microg/kg), the rats showed significant attenuation of locomotor
      activity. IND (10 mg/kg) treatment abolished the inhibitory effect of LPS on
      locomotor activity, and NLTX (1 mg/kg) also improved the decrease in locomotion 8
      hr after LPS treatment. 5. Plasma tumor necrosis factor (TNF)-alpha concentration
      dramatically increased 1 hr after the injection of 400 microg/kg LPS, and
      returned almost to the basal level 3 hr later. Next, rats were injected with 50
      microg/kg TNF-alpha intraperitoneally, and body weight change and DOI-induced WDS
      was determined 3 hr after TNF-alpha injection. Body weight loss was significantly
      greater in rats treated with TNF-alpha. On the other hand, DOI-induced WDS was
      not altered when rats were treated with TNF-alpha. 6. These results suggest that
      acute treatment with LPS inhibited 5-HT2A receptor-mediated behavior via
      cyclooxygenase and opioid receptor activation, but that the inhibition of the WDS
      by LPS appears to be independent of TNF-alpha production.

PMID- 11294486
TI  - Effect of cholecystokinin-8 microinjection into ventral tegmental area on
      dopamine release in nucleus accumbens of rats: an in vivo voltammetric study.
AB  - 1. Effects of microinjection of cholecystokinin-8 (CCK-8) into the rat ventral
      tegmental area were studied on dopamine (DA) release from nucleus accumbens
      (Acb), using fast cyclic voltammetry and carbon fibre microelectrode. 2. DA
      release was evoked by electrical stimulation of the medial forebrain bundle
      (MFB). DA release from Acb was increased with increasing intensity or frequency
      of electrical stimulation in a dose-dependent manner and was inhibited by
      microinjection of CCK-8 (0.5 microg/kg) into the ventral tegmental area. 3. The
      release of DA was clearly reduced at all the intensities (0.25, 0.5, 0.75 and 1.0
      mA) tested following CCK injection into the VTA, which was statistically
      significant (P<0.05). But the reduced percentage of DA release did not show
      significant changes between the data obtained with stimuli of different
      intensities (P>0.05). 4. While no change could be found with the stimuli of 10Hz,
      the DA release was significantly suppressed by injection of CCK-8 at the other
      three frequencies tested (50 Hz, 100 Hz and 250 Hz). Furthermore, although the
      differences in the reduced amounts of DA release obtained at 50 Hz, 100 Hz and
      250 Hz were statistically significant, the reduced percentage seemed to be not
      closely related to the frequency applied (P>0.05). 5. These results indicate that
      CCK-8 is involved in the regulation of midbrain DA neurotransmission, and thereby
      implicated in disorders, such as Parkinson's disease, that involve malfunctions
      of the basal ganglion DA neuronal systems.

PMID- 11294485
TI  - Activation of the dopaminergic system of medial prefrontal cortex of gerbils
      during formation of relevant associations for the avoidance strategy in the
      shuttle-box.
AB  - 1. A detailed analysis of behavior is a prerequisite for identification of
      components of information processing during learning. 2. Components of shuttle
      box learning like the signal detection and signal evaluation can be
      differentiated using behavioral events such as the attention response and the
      orienting response. 3. Chiefly during evaluation of signal meaning in the
      acquisition phase of the avoidance strategy the extracellular DA is increased in
      mPFC. 4. The kinetics of prefrontal dopaminergic activation from trial to trial
      depends on the stage of avoidance learning. 5. The increase of DA in mPFC can be
      an indicator for the involvement of working memory principles in signal
      evaluation stages of conditioning.

PMID- 11294487
TI  - Effects of antidepressant treatments on first-ECT seizure duration in depression.
AB  - 1. Current guidelines on the practice of Electroconvulsive Therapy (ECT) suggest
      that antidepressant medications should be discontinued prior to the course of
      therapy. However, the practice of withholding potentially helpful medication is
      debatable because the effects of these medications on seizure duration remain
      unclear. In particular, there is a lack of empirical knowledge about the effects
      of Selective Serotonin Reuptake Inhibitors (SSRIs) on ECT treatment. 2.
      Therefore, we investigated and compared the effects of SSRIs and tricyclic
      antidepressants (TCAs) on seizure duration after the first bilateral ECT
      treatment. 3. The diagnosis of major depressive disorder was made using the DSM
      IV criteria. Both patient groups were age- and sex-matched. ECT was indicated for
      acute suicidal acts or refractoriness to medications. All patients had received
      antidepressant treatment for at least eight weeks and were receiving at least the
      recommended dose of medication. All patients were ECT treatment-naive and we
      measured the seizure duration after the first bilateral ECT treatment. 4. There
      was no significant difference between electrical charge applied to either group.
      Between the TCA and SSRI group the seizure duration was not significantly
      different: 33.2 seconds and 31.4 seconds respectively.

PMID- 11294488
TI  - [18F]FDG-PET study in dementia with Lewy bodies and Alzheimer's disease.
AB  - 1. The authors report two siblings with dementia with Lewy bodies (DLB). Both the
      older brother and the younger sister underwent positron emission tomography (PET)
      studies with [18F]-2-fluoro-deoxy-D-glucose (FDG) during life. The FDG-PET study
      demonstrated unique and pronounced metabolic impairment in the occipital cortex
      in both patients. The clinical diagnosis of DLB in the sister was confirmed by
      autopsy. 2. FDG-PET images from 11 patients with Alzheimer's disease (AD), 7
      patients with DLB and 10 age-matched normal subjects were obtained and analyzed
      by the statistical parametric mapping (SPM) method. The SPM demonstrated a
      widespread metabolic reduction in the DLB group. The reduction was particularly
      pronounced in the visual association cortex in the DLB group compared to the AD
      group irrespective of clinical severity of the disease. 3. These findings suggest
      that functional neuroimaging techniques, including FDG-PET, will provide a
      valuable diagnostic aid to differentiate DLB from AD, and this will help detect
      DLB patients in the early stage of the disease.

PMID- 11294489
TI  - Dose-dependent augmentation effect of bromocriptine in a case with refractory
      depression.
AB  - 1. A 52-year-old female with refractory depression had not responded to various
      treatments including electroconvulsive therapy and augmentation therapy with
      lithium or triiodothyronine. 2. Addition of bromocriptine 2.5-5 mg/day to
      imipramine improved her depressive symptoms. However, when the dose was increased
      to 15 mg/day to treat residual depressive symptoms, her clinical status
      deteriorated and returned to the original level. The dose reduction to 5mg/day
      again improved her depressive symptoms. 3. This report confirms the augmentation
      effect of bromocriptine for refractory depression. It also suggests that there is
      dose-dependency in this effect.

PMID- 11294490
TI  - Impaired glucose tolerance without hypertriglyceridemia does not enhance
      postprandial lipemia.
AB  - Postprandial lipemia has been thought to be one of risk factors for coronary
      heart disease, and enhances in potential patients for atherosclerotic disease.
      Patients with impaired glucose tolerance (IGT) often show hypertriglyceride,
      which is caused by enhanced portprandial lipemia. Therefore, postprandial lipemia
      in patients with IGT and without hypertriglyceridemia has not been cleared. We
      have examined the levels of plasma triglyceride and chylomicron remnants after a
      high fat meal load (1250 kcal, 40% fat and 420 mg cholesterol) in 13
      normotriglyceridemic subjects with IGT and 10 controls with normal glucose
      tolerance (NGT). Chylomicron remnants were evaluated as remnant-like particles
      (RLP) that were not bound to an immunoaffinity gel mixture containing apo A-I and
      apo B-100 monoclonal antibody. RLP cholesterol levels 4 hours after the fat load
      were significantly lower in IGT subjects than in NGT subjects. Increase of RLP
      cholesterol after the fat meal load only significantly correlated with increase
      of insulin during the first 30 min after a 75 g oral glucose tolerance test, but
      not fasting lipid, insulinogenic index and HOMA-R (homeostasis model) in all
      subjects. These results suggest that postprandial response does not enhance in
      IGT subjects, and may associate with early-phase insulin secretion and without
      insulin resistance in normotriglyceridemic men with IGT or NGT.

PMID- 11294491
TI  - Simultaneous quantitative determination of alloxan, GSH and GSSG by HPlc.
      Estimation of the frequency of redox cycling between alloxan and dialuric acid.
AB  - This in vitro study compares the frequency of redox cycling between alloxan and
      dialuric acid at different initial ratios of glutathione and alloxan. Alloxan
      oxidizes GSH to GSSG. The rate of GSH oxidation at a given initial GSH
      concentration of 2.0 mmol/L depends on the initial concentration of alloxan
      added. The higher the concentration of alloxan in relation to the initial
      concentration of GSH, the faster GSH oxidation proceeds, as well as oxygen
      consumption, and therefore, formation of reactive oxygen species. The highest
      rates of GSH oxidation, i.e. GSSG formation, were found at concentration ratios
      of between 2.0 mmol/L GSH and 0.2 and 0.04 mmol/L alloxan, respectively. Because
      0.04 mmol/L alloxan oxidizes 2.0 mmol/L GSH completely, a frequency of at least
      25 cycles between alloxan and dialuric acid within 3 hours can be assumed. During
      each redox cycle, two molecules of GSH are oxidized to one molecule of GSSG, and
      during each cycle one molecule of oxygen is reduced simultaneously to one
      molecule of hydrogen peroxide. In total, therefore, one molecule of alloxan
      oxidizes at least 50 molecules of GSH and forms about 25 molecules of hydrogen
      peroxide.

PMID- 11294492
TI  - Atherosclerosis in apolipoprotein E-deficient mice is decreased by the
      suppression of endogenous sex hormones.
AB  - To elucidate the influence of gonadotropins, endogenous sex hormones and
      testosterone on atherosclerosis, 4-week-old male and female apoE-deficient mice
      received either 100 microg subcutaneous injections of the gonadotropin-releasing
      hormone (GnRH) antagonist Cetrorelix every 48 hours or a subcutaneous
      implantation of a permeable silastic tube with 35 mg of testosterone. Control
      mice received either subcutaneous injections of saline, a silastic implant with
      saline, or no treatment. The animals were sacrificed after eight weeks of
      treatment; blood was obtained by cardiac puncture and the aorta was taken out and
      prepared. The suppression of testosterone led to an increase in atherosclerosis
      in both the sinus aortae and the ascending aorta despite increases of cholesterol
      in male and decreases of HDL cholesterol in female mice. Treatment with
      testosterone led to small but significant increases of cholesterol levels and
      atherosclerotic lesions in male mice. Female mice showed no change in lipids and
      fewer atherosclerotic lesions. In conclusion, the suppression of gonadotropins
      appears to have a moderate anti-atherogenic effect. The effect of testosterone
      appears to be either neutral or opposed by gonadotropins.

PMID- 11294493
TI  - Sensitive assay to detect thyroid stimulating antibody (TSAb) in the presence of
      thyroid stimulation blocking antibody (TSBAb) in serum.
AB  - The detection of thyroid stimulating antibody (TSAb) activity in the presence of
      thyroid stimulation blocking antibody (TSBAb) in Graves' serum is difficult
      because TSBAb blocks TSAb activity. We recently demonstrated that polyethylene
      glycol (PEG) augments TSAb activity in porcine thyroid cells (PTC) assay. This
      PEG-induced augmentation makes it possible to develop a sensitive assay to detect
      TSAb in the presence of TSBAb. We studied the effects of PEG on TSAb- and TSBAb
      activities in PTC using 4 different preparations of the samples; (1) crude IgG
      using PEG 22.5% precipitated fraction (PF) from Graves' serum (0.2 ml), (2) crude
      IgG using PEG 12.5% PF, (3) serum (50 microl), and (4) serum (50 microl) in the
      presence of 5% PEG (final). When the effects of PEG on TSAb activity using crude
      IgG were examined, PEG 22.5% PF showed significantly higher TSAb activity than
      PEG 12.5% PF as reported previously. The augmentative effect of PEG on TSAb
      activity was also observed by the addition of 5% PEG to serum. We also
      demonstrated that PEG augmented TSAb-activities even in TSBAb-positive serum by
      two methods (crude IgG using PEG 22.5% PF and the addition of 5% PEG to serum).
      TSBAb activities were expressed by two calculation methods (A= [1 - (a - b)/(c -
      d) x 100] and B = [1 - (a - d)/(c - d) x 100], where a is cAMP produced in the
      presence of bTSH and patient's IgG, b is cAMP produced in the presence of
      patient's IgG, c is cAMP produced in the presence of bTSH and normal IgG, and d
      is cAMP produced in the presence of normal IgG). In the presence of TSAb, the
      values of A method were always higher than those of B method, since TSAb
      stimulated cAMP synthesis. We have developed two sensitive methods to detect TSAb
      even in the presence of TSBAb in serum using PEG; 1) incubation of crude IgG
      using PEG 22.5% PF from serum (0.2 ml), and 2) co-incubation of 5 % PEG with test
      serum (50 microl).

PMID- 11294494
TI  - Utilisation of intramyocellular lipids (IMCLs) during exercise as assessed by
      proton magnetic resonance spectroscopy (1H-MRS).
AB  - Recently, a 1H-MRS method became available to quantify intramyocellular lipids
      (IMCL) non-invasively. Currently, little is known about the regulation of this
      lipid pool. During prolonged exercise of moderate intensity, non-plasma-derived
      fatty acids play an important role as an energy source; lipids located within the
      skeletal muscle are considered to be a major source for these fatty acids. To see
      whether IMCL are reduced by exercise, 12 male runners were studied before and
      after exercising at different workloads and duration. Six subjects participated
      in a non-competitive run (NCR), three runners in a competitive half marathon (HM,
      21 km) and another three in a competitive marathon (M, 42 km). Intra- and
      extramyocellular lipids were quantified by 1H-MR spectroscopy in the tibialis
      anterior (TA) and soleus (SOL) muscles prior to and after the exercise bout.
      Moderate intensity (MI; 60-70% VO2max in NCR) with a mean exercise time (MET)
      ranging between 105-110 min decreased IMCL by 10 - 36% in both muscles. Prolonged
      MI exercise (MET 210-240 min; 68-70% VO2max in M) reduced IMCL by 42-57% in TA
      and 27 - 56% in SOL. In contrast, high intensity exercise (HI; MET 80-120 min; 83
      85% VO2max in HM) did not alter IMCL in either muscle. Extramyocellular lipids
      (EMCL) did not show any significant change in any group. The data show that one
      bout of moderate-intensity (60-70% VO2max) aerobic exercise markedly reduces the
      IMCL in TA and SOL muscles in a time-dependent fashion as assessed by 1H-MRS.
      However, exercise of similar duration but higher workload (> 80% VO2max) does not
      reduce IMCL. These data suggest that both exercise duration and workload are
      important factors in determining the reduction of IMCL.

PMID- 11294495
TI  - Stimulation of arterial smooth muscle cell proliferation by remnant lipoprotein
      particles isolated by immuno-affinity chromatography with anti-apo A-I and anti
      apo B-100.
AB  - Postprandial lipidemia, characterized by high plasma triglyceride-rich
      lipoprotein remnants, is associated with atherosclerosis. It has also been known
      that proliferation of vascular smooth muscle cells is crucial for the development
      of atherosclerosis. In this study, we investigated the direct effect of remnant
      lipoprotein particles, which consist of chylomicron remnants and very low density
      lipoprotein remnants, on vascular smooth muscle cell proliferation. Blood was
      collected from six patients with postprandial lipidemia two hours after their
      usual meal. Remnant lipoprotein particles were isolated from plasma by immuno
      affinity chromatography containing two monoclonal antibodies, anti-apo A-I (H-12)
      and anti-apo B-100 (JI-H). Remnant lipoprotein particles, as well as betaVLDL,
      significantly stimulated the proliferation of porcine coronary artery smooth
      muscle cells in a concentration-dependent manner, whereas very low density
      lipoprotein (d < 1.006) was virtually ineffective. These observations are
      consistent with recent reports that triglyceride-rich lipoprotein remnants, which
      are rich in apo E as well, are atherogenic.

PMID- 11294496
TI  - Effect of GLP-1 on lipid metabolism in human adipocytes.
AB  - We have studied the effect of several doses of GLP-1, compared to that of insulin
      and glucagons, on lipogenesis, lipolysis and cAMP cellular content, in human
      adipocytes isolated from normal subjects. In human adipocytes, GLP-1 exerts a
      dual action, depending upon the dose, on lipid metabolism, being lipogenic at low
      concentrations of the peptide (ED50, 10(-12) M), and lipolytic only at doses 10
      100 times higher (ED50, 10(-10) M); both effects are time- and GLP-1
      concentration-dependent. The GLP-1 lipogenic effect is equal in magnitude to that
      of equimolar amounts of insulin; both hormones apparently act synergically, and
      their respective action is abolished by glucagon. The lipolytic effect of GLP-1
      is comparable to that of glucagon, apparently additive to it, and the stimulated
      value induced by either one is neutralized by the presence of insulin. In the
      absence of IBMX, GLP-1, at 10(-13) and 10(-12) M, only lipogenic doses, does not
      modify the cellular content of cAMP, while from 10(-11) M to 10(-9) M, also
      lipolytic concentrations, it has an increasing effect; in the presence of IBMX,
      GLP-1 at already 10(-12) M increased the cellular cAMP content. In human
      adipocytes, GLP-1 shows glucagon- and also insulin-like effects on lipid
      metabolism, suggesting the possibility of GLP-1 activating two distinct
      receptors, one of them similar or equal to the pancreatic one, accounting cAMP as
      a second messenger only for the lipolytic action of the peptide.

PMID- 11294497
TI  - Ontogeny of 11beta-hydroxysteroid dehydrogenase: activity in the placenta,
      kidney, colon of fetal rats and rabbits.
AB  - Mechanisms to regulate closely fetal GC exposure are of considerable importance,
      as certain organs (kidney, brain) are adversely affected by excess GCs. 11beta
      Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) reduces transplacental passage
      of maternal GCs to the fetus. We hypothesized that 11beta-HSD2, if active in
      fetal kidney and colon, might allow local tissue modulation of GC access during
      the critical last trimester. We determined the presence, ontogeny and
      functionality of 11beta-HSD in the placenta and fetal, neonatal and adult kidney
      and colon in rats and rabbits and the cortisol:cortisone ratio in human amniotic
      fluid, which represents fetal urine. There was clear a 11beta-HSD2 expression in
      last trimester fetal colon, kidney and placenta in both rats and rabbits. This
      appeared of functional importance, since the potency of cortisol on fetal rabbit
      colonic sodium flux in the Ussing chamber was increased by 11beta-HSD inhibition.
      In human amniotic fluid, we found a decreasing ratio of cortisol:cortisone across
      the last trimester, suggesting an analogous onset of renal 11beta-HSD2 activity
      in the human fetal kidney. Local fetal tissue 11beta-HSD2 may modulate exposure
      to the deleterious effects of GCs upon target tissue maturation during sensitive
      periods of late gestation when fetal GC levels rise to prepare other organs
      (lung) for adaptations at birth.

PMID- 11294498
TI  - Diabetogenic transferrin damages podocytes in early human diabetic nephropathy.
AB  - The exact mechanisms by which growth hormone (GH) damages the kidney inducing
      diabetic nephropathy has not yet been elucidated. Recently, it has been shown
      that transferrin has the same diabetogenic effects of GH, being its mediator.
      Transferrin was studied using immunohistochemistry and immunoelectron microscopy
      in cases of early diabetic nephropathy, and in controls. Transferrin was only
      found in diabetic cases in podocytes and Bowman's capsule cells, but also in the
      tubular cells of both diabetic and non-diabetic controls. Immuno-electron
      microscopy for the presence of transferrin showed positive signals in the
      cytoplasm of diabetic podocytes, but not in pedicels. This selective deposition
      was associated with signs of organelle and cytoskeleton damage. On the basis of
      previous evidence and present glomerular findings, these results suggest an
      indirect diabetogenic effect on the kidney by GH mediated through transferrin.

PMID- 11294499
TI  - A novel use of the hyperinsulinemic-euglycemic clamp technique to estimate
      insulin sensitivity of systemic lipolysis.
AB  - The aim of the present study was to assess whether a standard hyperinsulinemic
      euglycemic clamp can provide an estimate for the antilipolytic insulin
      sensitivity. For this purpose, we infused 9 non-obese, healthy volunteers with
      [2H5]glycerol and used the glycerol rate of appearance (Ra) in plasma as an index
      for systemic lipolysis during a standard (1 mU/kg x min, 120 min) and a 3-step
      (0.1, 0.25, 1.0 mU/kg x min) hyperinsulinemic-euglycemic clamp. The insulin
      concentration, which half-maximally suppressed lipolysis (EC50) in the three-step
      clamp, was considered to be the gold standard for the antilipolytic insulin
      sensitivity. Glycerol Ra decreased from 1.53+/-0.11 micromol/kg x min to 0.60+/
      0.09 micromol/kg x min (p <0.001) during the standard clamp. The decrease in Ra
      at most time points during the standard clamp significantly correlated with the
      EC50. The highest correlation for the % decrease of glycerol Ra from baseline was
      found at 60 min (r = 0.96, p < 0.001) making this parameter a useful index for
      the antilipoytic insulin sensitivity. Neither plasma glycerol nor plasma free
      fatty acid (FFA) concentrations were significantly correlated with the EC50. In
      conclusion, the standard hyperinsulinemic-euglycemic clamp in combination with
      isotopic determination of glycerol Ra provides a reasonable estimate for the
      antilipolytic insulin sensitivity. In healthy subjects, the parameter best suited
      to estimate the insulin EC50 (by linear correlation) was the percentage decrease
      of glycerol Ra at 60 min.

PMID- 11294500
TI  - Decrease of hypothalamic neuropeptide Y gene expression by vanadyl sulfate in
      streptozotocin-induced diabetic rats.
AB  - In an attempt to elucidate the effect of vanadium compounds on the gene
      expression of neuropeptide Y (NPY), vanadyl sulfate (VOSO4) was orally
      administrated at the dose of 1 mg/kg body weight into streptozotocin-induced
      diabetic rats (STZ-diabetic rats) three times daily for 1 week. We found a marked
      lowering of plasma glucose with a significant decrease of food and water intake
      in these STZ-diabetic rats treated with VOSO4, although the weight gain was
      unaffected. The increase of hypothalamic NPY, both the mRNA level and peptide
      concentration, in STZ-diabetic rats was also reduced by this oral treatment of
      VOSO4. However, similar treatment of VOSO4 in normal rats failed to modify the
      feeding behavior and hypothalamic NPY gene expression. These data suggest that
      decrease of hypothalamic NPY gene expression by VOSO4 is related to the recovery
      of hyperphagia in diabetic rats lacking insulin.

PMID- 11294501
TI  - Glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with N
      acetylneuraminic acid exhibits selective activities in vivo and altered tissue
      distribution.
AB  - In order to study the effect of glycosylation on its biological activities and to
      develop IL-1 with less deleterious effects, N-acetylneuraminic acid (NeuAc) with
      C9 spacer was chemically coupled to human recombinant IL-1alpha. NeuAc-coupled IL
      1alpha (NeuAc-IL-1alpha) exhibited reduced activities in vitro and receptor
      binding affinities by about ten times compared to IL-1alpha. In this study, we
      examined a variety of IL-1 activities in vivo. NeuAc-IL-1alpha exhibited a marked
      reduction in the activity to up-regulate serum IL-6, moderate reduction in the
      activities to up-regulate serum amyloid A and NOx. However, it exhibited
      comparable activities as IL-1alpha to down-regulate serum glucose and to improve
      the recovery of peripheral white blood cells from myelosuppression in 5
      fluorouracil-treated mice. In addition, tissue level of NeuAc-IL-1alpha was high
      compared to IL-1alpha. These results indicate that coupling with NeuAc enabled us
      to develop neo-IL-1 with selective activities in vivo and enhanced tissue level.

PMID- 11294502
TI  - Synthesis of N-linked pentasaccharides with isomeric glycosidic linkage.
AB  - As part of a program to explore the structural requirement of N-glycans in the
      carbohydrate-mediated biological interactions, N-linked pentasaccharide core
      structure was stereochemically modified in terms of glycosidic linkage. Three
      isomers, alpha-D-Man-(1-->3)-[alpha-D-Man-(1-->6)]-alpha-D-Man-(1-->4)-beta-D
      GlcNAc-(1-->4)-beta-D-GlcNAc-L-Asn, alpha-D-Man-(1-->3)-[alpha-D-Man-(1-->6)]
      beta-D-Man-(1-->4)-alpha-D-GlcNAc-(1-->4)-beta-D-GlcNAc-L-Asn, and alpha-D-Man-(1
      ->3)-[alpha-D-man-(1-->6)]-alpha-D-Man-(1-->4)-alpha-D-GlcNAc-(1-->4)-beta-D
      GlcNAc-L-Asn, were synthesized. Synthesis of the pentasaccharide with natural
      linkage is also described.

PMID- 11294503
TI  - Kinetic study of a thermostable beta-glycosidase of Thermus thermophilus. Effects
      of temperature and glucose on hydrolysis and transglycosylation reactions.
AB  - A beta-glycosidase of a thermophile, Thermus thermophilus, belonging to the
      glycoside hydrolase family 1, was cloned and overexpressed in Escherichia coli.
      The purified enzyme (Ttbetagly) has a broad substrate specificity towards beta-D
      glucoside, beta-D-galactoside and beta-D-fucoside derivatives. The
      thermostability of Ttbetagly was exploited to study its kinetic properties within
      the range 25-80 degreesC. Whatever the temperature, except around 60 degreesC,
      the enzyme displayed non-Michaelian kinetic behavior. Ttbetagly was inhibited by
      high concentrations of substrate below 60 degreesC and was activated by high
      concentrations of substrate above 60 degreesC. The apparent kinetic parameters
      (kcat and Km) were calculated at different temperatures. Both kcat and Km
      increased with an increase in temperature, but up to 75 degreesC the values of
      kcat increased much more rapidly than the values of Km. The observed kinetics
      might be due to a combination of factors including inhibition by excess substrate
      and stimulation due to transglycosylation reactions. Our results show that the
      substrate could act not only as a glycosyl donor but also as a glycosyl acceptor.
      In addition, when the glucose was added to reaction mixtures, inhibition or
      activation was observed depending on both substrate concentration and
      temperature. A reaction model is proposed to explain the kinetic behavior of
      Ttbetagly. The scheme integrates the inhibition observed at high concentrations
      of substrate and the activation due to transglycosylation reactions implicating
      the existence of a transfer subsite.

PMID- 11294504
TI  - Terminal glycosylation of cystic fibrosis airway epithelial cells.
AB  - Cystic fibrosis (CF) has a characteristic glycosylation phenotype usually
      expressed as a decreased ratio of sialic acid to fucose. The glycosylation
      phenotype was found in CF/T1 airway epithelial cells (deltaF508/deltaF508). When
      these cells were transfected and were expressing high amounts of wtCFTR, as
      detected by Western blot analysis and in situ hybridization, the cell membrane
      glycoconjugates had an increased sialic acid content and decreased fucosyl
      residues in alpha1,3/4 linkage to antennary N-acetyl glucosamine
      (Fuc(alpha)1,3/4GlcNAc). After the expression of wtCFTR decreased, the amount of
      sialic acid and Fuc(alpha)1,3/4GlcNAc returned to levels shown by the parent CF
      cells. Sialic acid was measured by chemical analysis and Fuc(alpha)1,3/4GlcNAc
      was detected with a specific alpha1,3/4 fucosidase. CF and non-CF airway cells in
      primary culture also had a similar reciprocal relationship between fucosylation
      and sialylation. It is possible that the glycosylation phenotype is involved in
      the pathogenesis of CF lung disease by facilitating bacterial colonization and
      leukocyte recruitment.

PMID- 11294505
TI  - Effect of 6-O-sulfonate hexosamine residue on anticoagulant activity of fully O
      sulfonated glycosaminoglycans.
AB  - Intact and fully O-sulfonated glycosaminoglycans (GAGs) including chondroitin
      sulfate, dermatan sulfate, hyaluronan, heparan sulfate and heparin were
      chemically de-O-sulfonated on their hexosamine C-6 position (6-O-desulfonation)
      using N,O-bis(trimethylsilyl) acetamide. 1H NMR spectroscopy and chemical
      compositional analysis showed that the chemical de-O-sulfonation at C-6 position
      of hexosamine residues in both intact and fully O-sulfonated GAGs was completely
      achieved. Since GAGs and their derivatives are often used as anticoagulant
      agents, their anti-amidolytic activities were determined. While most of
      anticoagulant activity of fully O-sulfonated GAGs (FGAGs) and heparin disappeared
      following chemical 6-O-desulfonation, the activity of 6-O-desulfonated fully O
      sulfonated dermatan sulfate (De6FDS) remained. This observation suggests the
      importance of the position of O-sulfonate groups for anti-coagulant activity.

PMID- 11294506
TI  - A sensitive mapping strategy for monitoring the reproducibility of glycan
      processing in an HIV vaccine, RGP-160, expressed in a mammalian cell line.
AB  - The external envelope glycoprotein (gp160) of HIV-1 is a candidate for vaccines
      against AIDS. Most of the surface of the molecule is shielded by carbohydrate and
      the structures and locations of these glycans may be important in defining the
      immunogenicity of the viral coat. Here we report a sensitive mapping strategy for
      profiling and analysing the N-glycosylation of gp160, based on chemical release
      of glycans, fluorescent labelling and HPLC analysis. This approach has been
      validated in terms of establishing the reproducibility of all steps in the
      analytical procedure and on overall reproducibility on a run-to-run and day-to
      day basis. The validated analysis technique was used to monitor the consistency
      of N-glycosylation of one rgp 160 vaccine candidate produced in baby hamster
      kidney (BHK) cell culture. It was demonstrated that the variation in the glycan
      profiles of 6 different lots was not statistically significant.

PMID- 11294507
TI  - Syntheses of alpha-dystroglycan derived glycosyl amino acids carrying a novel
      mannosyl serine/threonine linkage.
AB  - Alpha-dystroglycan (alpha-DG) is a membrane-associated, extracellular
      glycoprotein. It is anchored to the cell-membrane by binding to the transmembrane
      glycoprotein beta-dystroglycan (beta-DG) to form an alpha/beta-DG-complex. It was
      discovered that the bovine peripheral nerve alpha-DG possesses the Ser/Thr linked
      tetrasaccharide as the major constituent of the O-linked carbohydrates, which was
      proposed to contribute laminin binding activity of this glycoprotein. This
      structure has a striking feature in terms of the mode of linkage between
      oligosaccharide and the core protein. It has a mannose residue linked to the core
      protein through Ser/Thr residue. A similar structure was proposed to exist in
      brain derived HNK-1 immunoreactive O-glycans. Being interested in the structural
      novelty and potential biological significance of this type of glycan chains, the
      chemical synthesis of Ser/Thr linked mannose containing tetrasaccharide was
      investigated. Tetrasaccharide donor was constructed from monosaccharide blocks
      and coupled with Ser/Thr derivatives. Subsequent deprotection afforded target
      tetraosyl serine. Furthermore, synthetic routes to lower homologues, namely Gal
      beta-(1,4)-GlcNAc-beta-(1,2)-Man-alpha-Ser and GlcNAc-beta-(1,2)-Man-alpha-Ser
      were also provided.

PMID- 11294508
TI  - Evaluation of synthetic schemes to prepare immunogenic conjugates of Vibrio
      cholerae O139 capsular polysaccharide with chicken serum albumin.
AB  - Vibrio cholerae serotype O139 is a new etiologic agent of epidemic cholera. There
      is no vaccine available against cholera caused by this serotype. V. cholerae O139
      is an encapsulated bacterium, and its polysaccharide capsule is an essential
      virulent factor and likely protective antigen. This study evaluated several
      synthetic schemes for preparation of conjugates of V. cholerae O139 capsular
      polysaccharide (CPS) with chicken serum albumin as the carrier protein (CSA)
      using 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) or 1-cyano-4
      dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents. Four
      conjugates described here as representative of many experiments were synthesized
      in 2 steps: 1) preparation of adipic acid hydrazide derivative of CPS (CPS(AH))
      or of CSA (CSA(AH)), and 2) binding of CPS(AH) to CSA or of CPS to CSA(AH).
      Although all conjugates induced CPS antibodies, the conjugate prepared by EDC
      mediated binding of CPS and CSA(AH) (EDC:CPS-CSA(AH)) was statistically
      significantly less immunogenic than the other three conjugates. Representative
      sera from mice injected with these three conjugates contained antibodies that
      mediated the lysis of V. cholerae O139 inoculum. Evaluation of the different
      synthetic schemes and reaction conditions in relation to the immunogenicity of
      the resultant conjugates provided the basis for the preparation of a V. cholerae
      O139 conjugate vaccine with a medically useful carrier protein such as diphtheria
      toxin mutant.

PMID- 11294509
TI  - Limited sampling strategies for estimating cyclosporin area under the
      concentration-time curve: review of current algorithms.
AB  - Cyclosporin, the drug of first choice in transplantation surgery, is
      characterized by a low therapeutic index and variable absorption, so close
      monitoring of the drug is required to optimize the dosing. Predose blood
      cyclosporin levels are measured routinely for therapeutic monitoring, but this
      approach is not optimal because the area under the concentration-time curve (AUC)
      correlates better with clinical events. However, conventional methods of
      measuring AUC require many blood samples, which is not viable in a routine
      clinical setting. AUC monitoring can be simplified for use in a clinical setting
      by using a limited sampling strategy (LSS) that allows AUC to be estimated using
      a small number of blood samples collected at specific times. This article reviews
      the current literature on estimating cyclosporin AUC using LSS. Thirty-eight
      papers suggesting the use of specific time points were found. LSS has been
      developed for different transplant types, with different dosing regimens, and
      with different assays. Most authors suggested either two- or three-sample
      equations. Results from authors who validated their models suggest that equations
      defined on one transplant type may be applicable to other transplant types, to
      both adults and children, and to early or late after transplantation. Moreover,
      it seems that there is flexibility in the choice of equations available to
      clinicians. The number of samples to collect for accurate estimations is a matter
      of debate, but a wise choice can minimize the number. The choice of the optimal
      LSS and validation are discussed.

PMID- 11294510
TI  - P-hydroxylation of phenobarbital: relationship to (S)-mephenytoin hydroxylation
      (CYP2C19) polymorphism.
AB  - The aim of the current study was to compare the pharmacokinetics of phenobarbital
      (PB) in extensive metabolizers (EMs) and poor metabolizers (PMs) of S
      mephenytoin. Ten healthy volunteers (5 EMs and 5 PMs) were given 30 mg PB daily
      for 14 days. PB and p-hydroxyphenobarbital (p-OHPB) in serum and urine were
      measured by high-performance liquid chromatography (HPLC). Urinary excretion
      (12.5% versus 7.7%) and formation clearance (29.8 versus 21.1 mL/h) of p-OHPB,
      one of the main metabolites of PB, were significantly lower (p < .05) in PMs than
      in EMs. However, area under the serum concentration-time curve (153.3 in the EMs
      versus 122.9 microg x h/mL in the PMs), total (210.8 versus 254.9 mL/h) and renal
      clearance (53.1 versus 66.1 mL/h) of PB were identical between the two groups. To
      compare the inducibility of CYP2C19, mephenytoin was also given prior to and on
      the last day of PB treatment. The urinary level of 4'-hydroxymephenytoin was
      analyzed by a validated gas chromatograpy/mass spectrometry (GC/MS) method. The
      mephenytoin hydroxylation index did not change in either EMs (1.42 versus 1.42)
      or PMs (341.4 versus 403.5), showing that CYP2C19 was not induced by treatment
      with PB. These results indicated that the p-hydroxylation pathway of PB co
      segregates with the CYP2C19 metabolic polymorphism. However, the overall
      disposition kinetics of PB were not different between EMs and PMs, and therefore
      polymorphic CYP2C19 seems have no major clinical implications.

PMID- 11294511
TI  - Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics
      of mycophenolic acid.
AB  - Mycophenolate mofetil (MMF) is almost completely absorbed from the gut and is
      rapidly de-esterified into its active drug, mycophenolic acid (MPA). The main
      metabolite is glucuronidated MPA (MPAG), which is excreted into bile and
      undergoes enterohepatic recirculation. Studies in healthy volunteers treated with
      cholestyramine show that interruption of the enterohepatic recirculation
      decreases MPA exposure by approximately 40%. Published data show a difference in
      mycophenolic acid plasma concentrations between kidney transplant recipients
      treated with MMF plus cyclosporine (CsA) and those treated with MMF plus
      tacrolimus (TRL). However, the interpretation of these data is complicated by
      interpatient differences in variables that may influence MMF pharmacokinetics
      (e.g., underlying disease, co-medication, and time since transplantation). To
      understand the influence of TRL and CsA on MMF pharmacokinetics (PK) more
      completely, the authors eliminated confounding variables in clinical studies by
      performing drug interaction studies in inbred rats. To achieve a steady state, 3
      groups of Lewis rats (n = 8 per group) were treated once daily with oral CsA (8
      mg/kg), TRL (4 mg/kg), or placebo on days 0-6 before all rats began once-daily
      oral treatment with MMF (20 mg/kg) on day 7. Combined treatment with either MMF +
      CsA, MMF + TRL, or MMF + placebo was continued for 1 week (days 8-14).
      Thereafter, CsA and TRL treatments were stopped but MMF treatment was continued
      on days 14-21. Blood was sampled during the 24 hours subsequent to dosing on day
      7 (after the first MMF dose), on day 14 (after multiple MMF doses) and on day 21
      (after CsA/TRL washout). Rats in the MMF + TRL group and in the MMF + placebo
      group showed a second peak in the MPA-PK profiles consistent with enterohepatic
      recirculation of MPA. The MPA-PK profiles for the MMF + CsA-treated animals did
      not show a second MPA peak. On Day 14, the mean plasma MPA-AUC(0-24 hours) for
      the CsA-treated animals was significantly less than MPA exposures for rats in the
      MMF + TRL- and the MMF + placebo-treated groups. Furthermore, in contrast to
      results from other investigators, co-administration of CsA and MMF significantly
      increased MPAG-AUC(0-24 hours). Serum creatinines did not differ among rats in
      the three groups. CsA but not TRL decreased MPA plasma levels and increased MPAG
      AUC(0-24 hours). These data suggest that CsA inhibits MPAG excretion into bile
      and offer an explanation for the well-known increased MPA exposure in organ
      transplant patients caused by conversion from CsA- to TRL-based
      immunosuppression.

PMID- 11294512
TI  - Failure of traditional trough levels to predict tacrolimus concentrations.
AB  - The objective of this study was to estimate tacrolimus population parameter
      values and to evaluate the ability of the maximum a posteriori probability (MAP)
      Bayesian fitting procedure to predict tacrolimus blood levels, using the
      traditional strategy of monitoring only trough levels, for dosage
      individualization in liver transplant patients. Forty patients treated with
      tacrolimus after liver transplantation were studied during the early
      posttransplant phase (first 2 weeks). This phase was divided into four time
      periods (1-4 days, 5-7 days, 8-11 days, 12-14 days). Tacrolimus was administered
      twice daily. Approximately one determination of a tacrolimus trough level on
      whole blood was performed each day. The NPEM2 program was used to obtain
      population pharmacokinetic parameter values. With each individual pharmacokinetic
      parameter estimated by the MAP Bayesian method for a given period, the authors
      evaluated the prediction of future levels of tacrolimus for that patient for the
      next period. This evaluation of Bayesian fitting predictive performance was
      performed using the USC*PACK clinical software. Mean pharmacokinetic parameter
      values were in the same general range as previously published values obtained
      with richer data sets. However, during each period, the percentage of blood
      levels predicted within 20% did not exceed 40%. The traditional strategy of
      obtaining only trough whole blood levels does not provide enough dynamic
      information for the MAP Bayesian fitting procedure (the best method currently
      available) to be used for adaptive control of drug dosage regimens for oral
      tacrolimus. The authors suggest modifying the blood concentration monitoring
      scheme to add at least one other concentration measured during the absorptive or
      distributive phase to obtain more information about the behavior of the drug. D
      Optimal design and similar strategies should be considered.

PMID- 11294513
TI  - Serum concentrations of 17beta-estradiol and estrone after multiple-dose
      administration of percutaneous estradiol gel in symptomatic menopausal women.
AB  - In two multicenter phase III efficacy studies, blood samples were obtained to
      evaluate the serum concentrations of 17beta-estradiol (E2) and unconjugated
      estrone (E1) after administration of a percutaneous gel or transdermal patch
      containing estradiol. In postmenopausal women, normal laboratory E2 and E1 serum
      concentrations range from 10-30 pg/mL and 20-40 pg/mL, respectively. Study
      subjects were healthy postmenopausal women with moderate to severe hot flushes
      occurring at least seven times daily or 60 times per week. Study 1 was a
      randomized, double-blind, multicenter study of percutaneous E2 gel 1.25 or 2.5 g
      (0.75 and 1.5 mg E2, respectively) versus placebo gel. Study 2 was a double-blind
      (blinded to E2 gel dose), randomized, active-controlled, multicenter, 12-week
      phase 3 study of E2 gel 0.625, 1.25, or 2.5 g (0.375, 0.75, or 1.5 mg E2,
      respectively) versus a transdermal E2 patch delivering 0.05 mg E2 per day. Serum
      E2 and E1 concentrations were evaluated at baseline and at week 12 for study 1
      and at baseline and weeks 4, 8, and 12 for study 2 using radioimmunoassay. Median
      serum concentrations of E2 after 1.25- and 2.5-g gel administration appeared to
      be dose-proportional throughout both studies. In study 1, the median serum
      concentrations of E2 at week 12 were 33.5 and 65.0 pg/mL for 1.25- and 2.5-g gel
      dose, respectively. The corresponding E1 values were 49.0 and 58.0 pg/mL. In
      study 2, both E2 and E1 concentrations were relatively stable at weeks 4, 8, and
      12. E2 values at week 12 for 0.625-, 1.25-, and 2.5-g gel doses and E2 patch were
      25.0, 32.0, 60.0, and 38.5 pg/mL, respectively. The corresponding E1 values were
      39.0, 41.0, 62.5, and 40.0 pg/mL. Application of the 1.25-g gel dose and a
      transdermal patch delivering 50 microg per day of E2 resulted in comparable
      median E2 and E1 concentrations. However, the 0.625-g gel dose did not produce E2
      levels in a range expected to be consistently therapeutic in most postmenopausal
      women.

PMID- 11294514
TI  - Serum concentrations of fluoxetine in the clinical treatment setting.
AB  - This article discusses fluoxetine serum concentrations as displayed in a clinical
      setting. A racemic serum fluoxetine and norfluoxetine high-performance liquid
      chromatography method, including ultraviolet light detection, was used for
      routine therapeutic drug monitoring (TDM) purposes. In all, 508 samples were
      analyzed. For the scientific investigation, predefined inclusion and exclusion
      criteria were applied and 150 samples representative of trough values in steady
      state conditions with essential clinical information provided on the assay
      request forms were evaluated. Fluoxetine plus norfluoxetine concentration-to-dose
      (C/D) ratio showed Gaussian distribution. Interindividual coefficients of
      variation of fluoxetine and norfluoxetine serum concentrations after different
      doses were found to be 40-63%. Intraindividual fluoxetine TDM variability was
      low. The Spearman rank correlation coefficient for fluoxetine and norfluoxetine
      C/D ratios in first and second samples was 0.68. Minor increases in norfluoxetine
      C/D and fluoxetine plus norfluoxetine C/D ratios were found in elderly patients
      compared with younger adult patients. A higher body-mass index was associated
      with minor decreases in fluoxetine and fluoxetine plus norfluoxetine C/D ratios.
      New fluoxetine pharmacokinetic data are added to the results from earlier phases
      of drug development. Moreover, the results of this study support the usefulness
      of a fluoxetine TDM procedure for individual dose optimization, detection of drug
      interactions, and assessments of patient compliance.

PMID- 11294516
TI  - Oxybutynin does not affect cyclosporin blood levels.
AB  - Cyclosporin is an important immunosuppressive medication used to prevent organ
      rejection. Drug interactions that alter its blood levels can cause serious
      problems with toxicity or transplant rejection. Current evidence indicates that
      both cyclosporin and oxybutynin, which is used to treat bladder dysfunction, are
      metabolized by the cytochrome P450 3A enzyme system, raising the possibility of
      an adverse interaction between these medications. However, a study of two
      children receiving cyclosporin with and without oxybutynin revealed no
      significant changes in trough blood cyclosporin concentrations.

PMID- 11294515
TI  - Performance characteristics of four free phenytoin immunoassays.
AB  - The measurement of the unbound or free phenytoin concentration is indicated in
      several situations, including uremia. In patients with uremia, metabolites of
      phenytoin and other substances accumulate and can displace phenytoin from its
      protein binding sites, with a consequent increase in the free fraction of drug.
      Some of the phenytoin metabolites that accumulate in uremia can cross-react with
      phenytoin immunoassays. In this study the authors evaluated four free phenytoin
      immunoassays compared with a high-performance liquid chromatography (HPLC)
      method: the Roche COBAS Integra, the Syva EMIT 2000, the Opus INNOFLUOR, and the
      Abbott TDx. All four methods demonstrated good precision, with interday
      coefficients of variation of < or = 5% and comparable recoveries using quality
      control material. Two of the methods, the EMIT 2000 and COBAS Integra, showed
      excellent agreement with the HPLC method using samples from patients both with
      normal renal function and with renal insufficiency. The other two methods, the
      INNOFLUOR and TDx, showed average positive biases for the therapeutic range of 3
      7% and 21-22%, respectively, compared with the HPLC method for samples from
      patients with normal renal function, and average positive biases of 24-32% and 75
      81%, respectively, with samples from patients with uremia.

PMID- 11294517
TI  - Therapeutic drug monitoring of haloperidol, perphenazine, and zuclopenthixol in
      serum by a fully automated sequential solid phase extraction followed by high
      performance liquid chromatography.
AB  - In Denmark, haloperidol, perphenazine, and zuclopenthixol are among the most
      frequently requested antipsychotics for therapeutic drug monitoring. With the
      number of requests made at the authors' laboratory, the only rational analysis is
      one that can measure all three drugs simultaneously. The authors therefore
      decided to develop an automated high-performance liquid chromatography (HPLC)
      method. Two milliliters serum, 2.0 mL 10 mmol/L sodium phosphate buffer (pH 5.5),
      and 150 microL internal standard (trifluoperazine) solution were pipetted into
      HPLC vials and extracted on an ASPEC XL equipped with 1 mL (50 mg) Isolute C2
      (EC) extraction columns and acetonitrile-methanol-ammonium acetate buffer
      (60:34:6) as extracting solution. Three hundred fifty microliters was analyzed by
      HPLC; a 150 x 4.6-mm S5CN Spherisorb column with a mobile phase of 10 mmol/L
      ammonium acetate buffer-methanol (1:9), a flow rate of 0.6-1.7 mL/min, and
      ultraviolet detection at 256 and 245 nm were used. Reproducibility was 5-12% and
      the lower limit of quantitation was 10, 1, and 5 nmol/L (4, 0.4, and 2 ng/mL) for
      haloperidol, perphenazine, and zuclopenthixol, respectively. The method was found
      to be sufficiently selective and robust for routine analysis.

PMID- 11294518
TI  - Simultaneous determination of plasma prednisolone, prednisone, and cortisol
      levels by high-performance liquid chromatography.
AB  - Recipients of organ transplants remain particularly dependent on prednisolone as
      part of their maintenance immunosuppression. Despite this, the pharmacokinetics
      of prednisolone have never been fully characterized in these patients, and
      consequently dosing remains empirical. Accurate monitoring of prednisolone, its
      primary metabolite prednisone, and endogenous cortisol suppression in such
      patients may provide a means of improving the clinical outcome by adjusting for
      variability in prednisolone pharmacokinetics and pharmacodynamics. Measurement of
      endogenous cortisol may provide an independent marker of prednisolone
      pharmacodynamics. A simple isocratic reverse-phase high-performance liquid
      chromatography procedure, using betamethasone as an internal standard, was
      developed to quantify plasma prednisolone, prednisone, and cortisol
      simultaneously. The steroids were extracted from 0.5 mL plasma with 3 mL (1:1
      v/v) ethyl acetate/tert-methyl butyl ether and 0.1 mL phosphoric acid, washed in
      0.1 mol/L NaOH before a final drying step and reconstitution in mobile phase for
      injection. Separation was achieved using a Supelcosil LC-18-DB, 150 x 4.6-mm, 5
      microm particle size, reverse-phase column attached to a Newguard 15 x 3-mm, RP8
      guard column maintained at 25 degreesC, with ultraviolet detector set at 254 nm.
      The mobile phase consisted of 16% isopropanol in water containing 0.1%
      trifluoroacetic acid, set at a flow rate of 1.2 mL/min. The assay was linear up
      to 1,002 microg/L for prednisolone, 982 microg/L for prednisone, and 545 microg/L
      for cortisol. Mean intra-assay and interassay imprecision levels were 6.0% and
      7.2%, respectively, for prednisolone, 5.8% and 7.2% for prednisone, and 5.6% and
      7.9% for cortisol. Intra-assay inaccuracy was <7% of nominal values for
      prednisolone, prednisone, and cortisol. The lower limit of quantification was 7
      microg/L for prednisolone and prednisone and 10 microg/L for cortisol.
      Corticosteroid recoveries were 73%, 74%, and 90% for prednisolone, prednisone,
      and cortisol, respectively. The authors describe a robust, inexpensive, and
      simple method suitable for therapeutic drug monitoring or pharmacokinetic studies
      of prednisolone; it may also be used to measure the suppression of endogenous
      cortisol production.

PMID- 11294519
TI  - Adsorptive voltametry to determine platinum levels in plasma from testicular
      cancer patients treated with cisplatin.
AB  - Patients cured of metastatic testicular cancer with cisplatin chemotherapy may
      suffer late adverse effects even after 20 years. The cause of these late adverse
      effects has not been elucidated yet. One cause might be prolonged tissue
      retention of platinum in these patients. Therefore, an extremely sensitive method
      for measuring platinum in plasma was used to investigate whether platinum is
      still detectable in plasma 10 to 20 years after cisplatin chemotherapy. High
      pressure decomposition of plasma is followed by adsorptive voltametric
      determination of platinum, with a limit of quantification of 6 pg/g plasma. This
      procedure appeared suitable for the measurement of platinum in 44 former patients
      with platinum levels ranging from 22 to 140 pg/g plasma. This method is
      approximately 6000 times more sensitive than the standard flameless atomic
      absorption spectrophotometry (AAS) method. The platinum levels of these 44
      patients were significantly elevated when compared with 20 control patients who
      were cured of testicular cancer but did not receive cisplatin chemotherapy (p <
      0.001). There was a significant correlation between plasma platinum
      concentrations and follow-up time after cisplatin administration (r = -0.658, p <
      0.001). This study shows that patients with testicular cancer who were treated
      with cisplatin can retain platinum in their body for at least 20 years. More data
      are needed to investigate whether there is a relation between the prolonged
      retention of platinum and long-term toxicity.

PMID- 11294520
TI  - In vitro stability of cocaine in whole blood and plasma including ecgonine as a
      target analyte.
AB  - The in vitro stability of cocaine (COC) was monitored in fresh whole blood and
      plasma stabilized with potassium fluoride (0.25%) for as long as 15 days. The
      samples were stored at 4 degreesC, 20 degreesC and 40 degreesC. Additionally,
      fresh plasma samples containing either benzoylecgonine (BZE), ecgonine methyl
      ester (EME) or ecgonine (ECG) were stored at 4 degreesC and 20 degreesC. Data
      were established using subsequent solid-phase extraction procedures and high
      performance liquid chromatography coupled to atmospheric pressure ionization mass
      spectrometry for isolation and quantitation of COC, BZE, EME, and ECG. COC, BZE,
      and EME concentrations decreased with increasing storage temperature and time
      after an apparent first-order reaction kinetic. Only ECG appeared to be stable at
      storage temperatures as high as 20 degreesC for the entire observation period. At
      40 degreesC, the amount of ECG produced from hydrolysis of COC still totalled 80%
      of the initial COC concentration. Hydrolysis of COC to EME occurred more rapidly
      in plasma than in blood. The dynamic degradation profiles obtained were dependent
      on the storage temperature. The conversion of COC to BZE, EME, and ECG appeared
      to be stoichiometric at all time intervals at storage temperatures of 4 degreesC
      and 20 degreesC. The presence of any hydrolysis product of COC in blood or plasma
      constitutes confirmatory evidence of COC incorporation, and determination of ECG
      seems most promising even in samples stored under unfavorable conditions.

PMID- 11294521
TI  - Simultaneous measurement of plasma ropivacaine and bupivacaine concentrations by
      HPLC with UV detection.
AB  - The authors developed a high-performance liquid chromatography (HPLC) assay for
      the simultaneous determination of plasma ropivacaine and bupivacaine
      concentrations using ultraviolet (UV) detection and a simple solid-phase
      extraction procedure. The absolute retention times of ropivacaine, bupivacaine,
      and the internal standard pentycaine were 1.9, 3.0, and 5.6 minutes,
      respectively. The assay had a linearity of 2000 ng/mL, a sensitivity of 5 ng/mL,
      an average recovery of 98%, and an average day-to-day imprecision of <10% for
      both drugs. A patient correlation study (n = 23) using this HPLC method and an
      established gas chromatographic assay revealed a slope of 1.01, an intercept of 
      10.6 ng/mL, and a correlation coefficient of 0.99 for ropivacaine; and a slope of
      0.96, an intercept of 14.7 ng/mL, and a correlation coefficient of 0.99 for
      bupivacaine. Of the 60 different drugs tested, only quinidine and lidocaine
      extracted but did not interfere with the measurement of the drugs of interest.
      The authors conclude that the method described here is ideally suited for the
      therapeutic monitoring of plasma ropivacaine and bupivacaine concentrations.

PMID- 11294522
TI  - The MEGX test: a tool for the real-time assessment of hepatic function.
AB  - The dynamic liver function test based on the hepatic conversion of lidocaine to
      monoethylglycinexylidide (MEGX) can complement established static liver function
      tests if prognostic information is of particular interest. Because of its ease of
      use and rapid turnaround, the MEGX test has found widespread application for
      realtime assessment of hepatic function in transplantation, critical care
      medicine, and various experimental models. Lidocaine is metabolized primarily by
      the liver cytochrome P450 system through sequential oxidative N-dealkylation, the
      major initial metabolite in humans being MEGX. Because of the relatively high
      extraction ratio of lidocaine, this liver function test depends not only on
      hepatic metabolic capacity but also on hepatic blood flow. For the determination
      of MEGX in serum, an immunoassay based on the fluorescence polarization
      immunoassay technique high-performance liquid chromatography and gas liquid
      chromatography methods have been described. Whereas high-performance liquid
      chromatography and gas liquid chromatography are specific for MEGX, the
      fluorescence polarization immunoassay also cross-reacts with 3-OH-MEGX. Although
      this is not a problem in humans, some species, such as the rat, produce
      significant amounts of this metabolite. The findings of most studies published so
      far suggest that the MEGX test is a useful tool that can improve our decision
      making process with respect to the selection of transplant candidates. Patients
      with a MEGX 15- or 30-minute test value <10 microg/L have a particularly poor 1
      year survival rate. Serial monitoring of liver graft recipients early after
      transplantation with the MEGX test may initially alert the clinician to a major
      change in liver function; if used with other tests, such as serum hyaluronic acid
      concentrations, it may become more discriminatory. In critically ill patients,
      several studies have shown that an initially rapid decrease in MEGX test values
      is associated with an enhanced risk for the development of multiple organ
      dysfunction syndrome and a poor outcome. Further, this decrease appears to be
      associated with an enhanced systemic inflammatory response. The MEGX test has
      potential for investigating the pathogenesis of multiple organ dysfunction
      syndrome with regard to early hepatic functional impairment in critically ill
      patients after polytrauma or sepsis.

PMID- 11294524
TI  - Urogynecology: the death of dogma.

PMID- 11294523
TI  - Inhibition of thrombin by iopromide in vitro.
AB  - Iopromide is a nonionic, iodinated, monomeric, radiographic contrast agent used
      in various indications, including coronary angiography and visceral and
      peripheral arteriography. Nonionic contrast media have been postulated to
      increase thrombogenicity when compared with ionic contrast media. The goal of
      this study was to characterize the interaction of iopromide with thrombin,
      specifically to determine the rate, extent, specificity, and reversibility of the
      thrombin inhibition by iopromide, the integrity of the thrombin-iopromide
      complex, and the inhibitory potency of iopromide using a validated assay
      methodology. Iopromide was mixed with purified thrombin or pooled serum from
      healthy male and female donors. The final concentrations of iopromide in the
      presence of estimated physiologic concentrations of thrombin (1 nmol/L) were 0
      184 mmol/L. After incubation for defined time intervals, the activity of thrombin
      was determined by adding substrate and measuring the absorbance of the generated
      chromophores at 405 nm. The possible inhibition of the protease trypsin by
      iopromide was investigated to evaluate the specificity of thrombin inhibition by
      iopromide. Iopromide was compared with Thromstop, a known thrombin inhibitor, to
      assess the relative potency of iopromide. The inhibition of thrombin by iopromide
      was immediate, rapidly reversible, and proportionate to the iopromide
      concentrations. The minimum inhibitory concentration of iopromide was 50 mmol/L.
      At the highest iopromide concentration tested, 184 mmol/L, the mean inhibition of
      thrombin activity was 44.5%. The mean concentration of iopromide associated with
      a 50% inhibition was 206 mmol/L. The inhibitory potency of iopromide was 4 x
      10(6) times smaller than that of Thromstop. The inhibition of thrombin by
      iopromide is specific, because trypsin was not inhibited by iopromide. The
      results indicate that in vitro iopromide at clinically relevant concentrations
      partially inhibits thrombin activity. However, the in vitro model used does not
      consider other factors that may be relevant for the overall coagulation response
      in vivo.

PMID- 11294526
TI  - A prospective clinical and urodynamic study of bladder function during and after
      pregnancy.
AB  - The aim of the study was to determine whether clinical and/or urodynamic changes
      in bladder function occur during pregnancy. Assessment consisted of a urinary
      symptom questionnaire, urogynecological examination and urodynamic
      investigations, which were repeated 6 weeks after pregnancy. Sixty-six patients
      had the initial and 40 the follow-up assessments. Statistical analysis was done
      by 95% confidence intervals (95% CI). Nocturia, frequency, dysuria, urgency and
      stress incontinence occurred significantly more frequently during pregnancy.
      Urinary tract infection was diagnosed in 18% of patients during pregnancy and
      asymptomatic bacteriuria in 9%. Genuine stress incontinence was diagnosed in 12%
      during pregnancy and in none after pregnancy (95% CI 1% to 24%). An unstable
      detrusor was diagnosed in 23% of patients during pregnancy and in 15% after
      pregnancy (95% CI -8% to 23%). Strong desire to void, urgency, maximum
      cystometric capacity, maximum flow rate and average flow rate were all
      statistically significantly decreased during pregnancy. It is concluded that
      significant changes occur in bladder function during pregnancy.

PMID- 11294525
TI  - A systematic review of estrogens for recurrent urinary tract infections: third
      report of the hormones and urogenital therapy (HUT) committee.
AB  - Our objective was to apply a meta-analysis to the available data to evaluate the
      effect of estrogen supplementation in the prevention of recurrent urinary tract
      infections in postmenopausal women. The literature review incorporated articles
      based on a search of Excerpta Medica, Medline, Science Citation Index and a
      manual search of commonly read journals in the fields of urology, gynecology,
      gerontology and primary healthcare, from January 1969 to December 1998. The
      search was not limited to English-language publications. Inclusion criteria were
      peer-reviewed articles containing original data with a primary outcome of
      symptomatic urinary tract infections and an estrogen-treated group. Articles were
      categorized into randomized controlled trials, case-control studies and self
      controlled series. Of the articles reviewed, five were randomized controlled
      trials, two were case-control studies and three were self-control series. Meta
      analysis of data from 334 subjects revealed a significant benefit from estrogen
      over placebo (odds ratio = 2.51, 95% confidence interval = 1.48 4.25). The most
      convincing results were obtained using the vaginal route of administration. A
      variety of different estrogen preparations have been employed in the few
      published reports, making comparison of the data difficult. However, vaginal
      administration seems to be effective in the prevention of recurrent urinary tract
      infections in postmenopausal women.

PMID- 11294527
TI  - Evaluation of pelvic floor muscle strength using four different techniques.
AB  - The aim of the study was to evaluate whether four different techniques were able
      to correctly measure pelvic floor muscle strength only. Sixteen volunteers
      performed a set of muscle contractions using the pelvic floor muscles (PFM) only,
      the abdominal muscles with and without PFM, gluteal muscles with and without PFM,
      adductor muscles with and without PFM and Valsalva maneuver with and without PFM.
      Pelvic floor muscle strength was evaluated by digital palpation, intravaginal
      EMG, pressure perineometry and perineal ultrasound. A 'non-pelvic muscle induced'
      reading was defined as a significant increase even though the pelvic floor
      muscles were not contracted. Results were as follows: isolated abdominal muscle
      contraction: non-pelvic muscle induced readings in 3/8 women with EMG and in 3/8
      with pressure perineometry; isolated gluteal muscle contraction: non-pelvic
      muscle induced readings in 1/2 women with EMG perineometry; isolated adductor
      muscle contraction: non-pelvic muscle induced readings in 6/11 women with EMG
      perineometry and in 2/11 women with pressure perineometry; Valsalva maneuver: non
      pelvic muscle induced readings in 4/9 women with EMG perineometry and 9/9 women
      with pressure perineometry. It was concluded that EMG and pressure perineometry
      do not selectively depict pelvic floor muscle activity.

PMID- 11294528
TI  - Outcome of Burch retropubic urethropexy and the effect of concomitant abdominal
      hysterectomy: a prospective long-term follow-up study.
AB  - A prospective follow-up study was performed to evaluate the effect of a
      concomitant abdominal hysterectomy with Burch colposuspension. Sixty-five women
      underwent Burch colposuspension (the Burch group) and 78 women colposuspension
      with concomitant abdominal hysterectomy (the hysterectomy group) during a 1-year
      period in Turku University Hospital. Subjective outcome was assessed with three
      questionnaires: at 6 weeks, 1 year, and a mean of 4.9 years after the operation.
      Complications related to the operation occurred in 19 patients (29.2%) in the
      Burch group and in 36 (46.2%) in the hysterectomy group (P = 0.038). No
      statistically significant difference in the frequency of any subgroup of
      complications was found. Instead, complications cumulated to fewer patients in
      the Burch group. During postoperative care in the hospital intermittent
      catheterization to treat transient urinary retention was needed more frequently
      in the Burch group than in the hysterectomy group (10.8% vs. 1.3%, P = 0.046). No
      significant difference was found in subjective short- and long-term outcome. In
      the long-term follow-up 79% were subjectively cured or improved, 77% in the Burch
      group and 81% in the hysterectomy group.

PMID- 11294529
TI  - Predictive value of clinical evaluation of stress urinary incontinence: a summary
      of the published literature.
AB  - Our objective was to evaluate the symptom and sign of stress incontinence in
      predicting the presence of urodynamically diagnosed genuine stress incontinence
      (GSI). The study was a computation of the sensitivity and predictive values from
      the published literature (1975-1998), evaluating the history and/or physical
      examination for the diagnosis of GSI, with calculation of efficacy variables.
      Results show that the isolated symptom of stress incontinence has a positive
      predictive value (PPV) of 56% for the diagnosis of pure GSI and 79% for GSI with
      additional abnormalities. The PPV of stress incontinence in association with
      other symptoms is 77% in detecting GSI (with or without additional
      abnormalities). A positive cough stress test has a PPV of 55% for detecting pure
      GSI and 91% for the mixed condition (GSI plus additional diagnosis). When
      isolated, the symptom or the sign of stress incontinence is a poor predictor of
      GSI. In combination, the prediction may be more promising.

PMID- 11294530
TI  - The urethral pressure profile and ultrasound imaging of the lower urinary tract.
AB  - In a prospective study 105 patients with symptoms of stress incontinence
      underwent video-urodynamic testing, including resting urethral pressure
      profilometry and translabial ultrasound. The urethral pressure profile (UPP)
      included maximum urethral closure pressure (MUCP), functional length (FL) and
      area under the curve (AUC). Ultrasound parameters included urethral thickness,
      urethral rotation and bladder neck descent, as well as funneling/opening of the
      internal urethral meatus on Valsalva maneuver. Levator contraction strength was
      assessed measuring the cranioventral displacement of the internal meatus.
      Negative correlations between UPP data and age, parity and previous surgery were
      observed which were consistent with literature data. There was a positive
      correlation between the urethral AP diameter on ultrasound and the MUCP, which
      agrees with reports showing reduced sphincter thickness or volume in stress
      incontinent women. Hypermobility on ultrasound did not correlate with UPP data.
      However, a lower MUCP correlated with extensive opening of the bladder neck.
      Finally, there was a trend towards poorer pelvic floor function with lower MUCP
      measurements.

PMID- 11294531
TI  - The clinical utility of a vaginal template designed to standardize suture
      placement during retropubic colposuspensions.
AB  - Suture placement and bite size utilizing a vaginal template are compared to a
      traditional surgical approach during modified retropubic colposuspension on four
      fresh-frozen human female cadavers. Overall, a larger suture bite was obtained
      utilizing the template (71.5 +/- 4.6 vs 46.7 +/- 25.3 mm2, P = 0.001). However,
      with increased surgical experience the suture bites obtained with the traditional
      approach and template technique were similar. Inconsistent suture placement
      relative to the urethrovesical junction and urethra was observed with both
      techniques. Differences in pelvic floor anatomy make consistent suture placement
      with respect to the urethrovesical junction and urethra neither possible nor
      entirely preferable with either technique. There seems to be little clinical
      value in the use of this vaginal template during modified retropubic
      colposuspensions.

PMID- 11294532
TI  - Low valsalva leak-point pressure and success of retropubic urethropexy.
AB  - The aim of this study was to determine whether an isolated low Valsalva leak
      point pressure (VLPP) is predictive of intrinsic sphincter deficiency (ISD) and
      can be an independent risk factor for retropubic urethropexy failure in patients
      with a normal maximal urethral closure pressure (MUCP). Twenty-four women with
      urodynamically proven genuine stress incontinence with low VLPP (<60 cmH2O) and
      normal MUCP (>20 cmH2O) were evaluated subjectively and objectively by complex
      urodynamic testing before and after undergoing a modified Burch urethropexy.
      Success rates were then compared to historical success rates for subjects with
      ISD treated with retropubic urethropexy using an exact one-sample test for
      binomial proportions. Patients were followed postoperatively for a mean of 11.1
      months, with a range of 5-16 months. Twenty-two of the 24 (91.7%) were continent
      on postoperative cystometry. This differs significantly from the published
      success rates of 50% (P < 0.001), if a low VLPP alone were predictive of ISD.
      Retropubic urethropexy was successful in the majority of our patients with
      genuine stress incontinence with a low VLPP and normal MUCP.

PMID- 11294534
TI  - Urge incontinence and detrusor instability.
AB  - Detrusor instability is a syndrome of urinary frequency, urgency and urge
      incontinence which can be demonstrated using urodynamic studies to document
      uninhibited bladder contractions. Idiopathic cases account for 90% and 10% are
      related to neurologic disorders. Several different treatment modalities are
      available, including bladder training/drill, electrical stimulation, medical and
      surgical therapies.

PMID- 11294533
TI  - Diagnosis and therapy of the female urethral diverticula.
AB  - The various diagnostic and therapeutic modalities currently in use for urethral
      diverticula are reviewed. Various radiographic techniques have been reported, but
      only voiding cystourethrography (VCUG) and positive-pressure urethrography (PPU)
      are currently utilized. Urethroscopy is another suitable technique for diagnosis.
      Various sonographic techniques have been proposed, but their sensitivity is
      improved only by the transvaginal approach and magnetic resonance imaging (MRI).
      Various treatment methods have been proposed. The standard operative approach is
      surgical, through the vagina. The techniques currently in use to treat urethral
      diverticula are the Spence procedure, the typical urethral diverticulectomy, and
      the Tancer partial ablation technique. A full history, and physical examination
      is the first step in screening. When the diagnosis is suspected ultrasound and
      radiological imaging is necessary. Sonography is the first non-invasive
      examination to be performed. In negative cases it is imperative to perform a PPU
      or MRI. Symptomatic and very large diverticula must be treated in the easiest way
      possible. The best treatment, except for complicated and infected diverticula, is
      excision.

PMID- 11294535
TI  - Laser welding of vesicovaginal fistula.
AB  - The management of vesicovaginal fistula remains a source of debate, despite
      extensive literature on the subject. It is difficult to prove the superiority of
      one surgical technique over another by randomized trials, given the variabilities
      of fistula etiology, the location and clinician expertise. Small epithelized
      fistulae following conservative treatment and residual or recurrent cases
      following transabdominal or transvaginal repair pose a therapeutic challenge. A
      case of a small vesicovaginal fistula following abdominal hysterectomy is
      presented, in which a successful outcome was achieved using endoscopic Nd-YAG
      laser fulguration.

PMID- 11294537
TI  - Nasalance scores in noncleft individuals: why not zero?
AB  - OBJECTIVE: To determine whether oral or nasal acoustic energy is primarily
      responsible for nonzero nasalance scores observed during the production of
      nonnasal sentences by individuals with normal speech. METHOD: Sixty adults with
      normal speech were asked to read the Zoo passage and produce three sustained
      vowels, (/i/, /a/ and /u/), with and without nares occlusion. RESULTS: There was
      a significant decrease in nasalance scores between the unoccluded and occluded
      conditions for all four stimulus pairs. The mean decrease across conditions
      ranged from 8 (/u/) to 25 (/i/). In the unoccluded condition, the nasalance score
      was significantly greater for /i/ than for the other stimuli. CONCLUSIONS: The
      findings suggest that the majority of acoustic energy detected by the nasometer's
      nasal microphone during the production of nonnasal utterances is the result of
      sound transmission through the nose. The data obtained during this investigation,
      coupled with information available from other studies, suggest that this may be
      due to transpalatal transmission. If correct, such a conclusion would have
      clinical implications for patients with palatal clefts, since residual structural
      abnormalities and scar tissue in a repaired cleft palate may increase, dampen, or
      in some way alter transpalatal acoustic transmission. Thus, surgical
      normalization of velopharyngeal port control may not be sufficient to eliminate
      hypernasality in all patients.

PMID- 11294536
TI  - The pain cycle: implications for the diagnosis and treatment of pelvic pain
      syndromes.
AB  - The aim of the study was to report our results of sacral nerve stimulation in
      patients with pelvic pain after failed conservative treatment. From 1992 to
      August 1998 we treated 111 patients (40 males, 71 females, ages 46 +/- 16 years)
      with chronic pelvic pain. All patients with causal treatment were excluded from
      this study. Pelvic floor training, transcutaneous electrical nerve stimulation
      (TENS) and intrarectal or intravaginal electrostimulation were applied and sacral
      nerve stimulation was used for therapy-resistant pain. The outcome of
      conservative treatment and sacral nerve stimulation (VAS <3/10; >50% pain relief)
      was related to symptoms of voiding dysfunction and dyschezia, and urodynamic
      proof of dysfunctional voiding, not to the pain localization or treatment
      modality. Outcome was inversely related to neuropathic pain. When conservative
      treatment failed, a test stimulation of the S3 root was effective in 16/26
      patients, and 11 patients were implanted successfully with a follow-up of 36 +/-
      8 months. So far no late failures have been seen. A longer test stimulation is
      needed in patients with pelvic pain because of a higher incidence of initial
      false positive tests. Our conclusion is that sacral nerve stimulation is
      effective in the treatment of therapy-resistant pelvic pain syndromes linked to
      pelvic floor dysfunction.

PMID- 11294538
TI  - Nasometric values for normal nasal resonance in the speech of young Flemish
      adults.
AB  - OBJECTIVE: The purpose of this study was to obtain normative nasalance scores for
      adult subjects speaking the Flemish language. Additional objectives of the study
      were to determine if speaker sex played a role in differences in nasalance scores
      and if significantly different nasalance scores existed for Flemish compared with
      other languages or dialects. DESIGN: Nasalance scores were obtained while young
      Flemish adults read three standard nasalance passages. These passages were an
      oronasal passage (a text that contained the same approximate percentage of nasal
      consonants as found in the standard Dutch speech), an oral passage (a text that
      excluded nasal consonants), and a nasal passage (a reading text loaded with nasal
      consonants). PARTICIPANTS: Subjects included 58 healthy young Flemish adults with
      normal oral and velopharyngeal structure and function, normal hearing levels,
      normal voice characteristics, and normal resonance and articulation skills.
      METHODS: The Nasometer (model 6200) was used to obtain nasalance scores for the
      three reading passages. These three reading passages were designed specifically
      for use with the nasometer. The nasalance data were analyzed for sex dependence,
      using Student's t test for each reading passage. This same test was used for
      comparison of our data with data of other languages. RESULTS: Normative nasalance
      data were obtained for the oronasal text (33.8%), the oral text (10.9%), and the
      nasal text (55.8%). Female speakers exhibited significantly higher nasalance
      scores than male speakers on the passages containing nasal consonants (normal
      text, p = .001; nasal text, p = .042). Furthermore, statistically significant
      cross-linguistic nasality differences were observed. The English and Spanish
      languages were found to have more nasalance than the Flemish language. For the
      North Dutch and Flemish languages, this cross-linguistic phenomenon was absent.
      CONCLUSION: These normative nasalance scores for normal young adults speaking the
      Flemish language provide important reference information for Flemish cleft palate
      teams. Sex-related differences and cross-linguistic differences were shown.

PMID- 11294539
TI  - Nasalance measures in Cantonese-speaking women.
AB  - OBJECTIVES: To establish and evaluate stimulus materials for nasalance
      measurement in Cantonese speakers, to provide normative data for Cantonese
      speaking women, and to evaluate session-to-session reliability of nasalance
      measures. PARTICIPANTS AND SETTING: One hundred forty-one Cantonese-speaking
      women with normal resonance who were students in the Department of Speech and
      Hearing Sciences, University of Hong Kong. PROCEDURES: Participants read aloud
      four speech stimuli: oral sentences, nasal sentences, an oral paragraph (similar
      to the Zoo Passage), and an oral-nasal paragraph (similar to the Rainbow
      Passage). Data were collected and analyzed using the Kay Nasometer 6200. Data
      collection was repeated for a subgroup of speakers (n = 28) on a separate day.
      Nasalance materials were evaluated by using statistical tests of difference and
      correlation. RESULTS: Group mean (standard deviation) nasalance scores for oral
      sentences, nasal sentences, oral paragraph, and oral-nasal paragraph were 16.79
      (5.99), 55.67 (7.38), 13.68 (7.16), and 35.46 (6.22), respectively. There was a
      significant difference in mean nasalance scores for oral versus nasal materials.
      Correlations between stimuli were as expected, ranging from 0.43 to 0.91. Session
      to-session reliability was within 5 points for over 95% of speakers for the oral
      stimuli but for less than 76% of speakers for the nasal and oral-nasal stimuli.
      CONCLUSIONS: Standard nasalance materials have been developed for Cantonese, and
      normative data have been established for Cantonese women. Evaluation of materials
      indicated acceptable differentiation between oral and nasal materials. Two
      stimuli (nasal sentences and oral paragraph) are recommended for future use.
      Comparison with findings from other languages showed similarities in scores;
      possible language-specific differences are discussed. Session-to-session
      reliability was poorer for nasal than oral stimuli.

PMID- 11294540
TI  - Social anxiety in Chinese adults with oral-facial clefts.
AB  - OBJECTIVE: This study examined social anxiety and measures of psychosocial
      adjustment in Chinese adults with oral-facial clefts, their unaffected siblings,
      and age-matched controls. DESIGN: This cross-sectional study utilized a matched
      case-control study design. PARTICIPANTS: Eighty-five adult cleft lip and cleft
      palate (CL/CP) subjects and 85 unaffected siblings (one adult sibling of each
      CL/CP subject) were recruited in Shanghai, China, from a larger CL/CP study.
      Eighty-five unaffected controls, gender- and age-matched to the CL/CP subjects,
      were recruited from Shanghai work units including factories, universities, and
      other institutions. OUTCOME MEASURES: Social Avoidance and Distress Scale, Fear
      of Negative Evaluation, Rosenberg Self-Esteem Scale, Interpersonal Support
      Evaluation List. RESULTS: Affected adults reported significantly more social
      anxiety than unaffected siblings and controls. Affected adults also scored
      significantly lower on measures of self-esteem and social support than unaffected
      siblings and controls. Unaffected siblings and controls were not found to differ
      on any of these measures. CONCLUSIONS: Findings suggest that individuals with
      oral-facial clefts may be more disadvantaged with respect to social affiliation
      and adaptation than unaffected adults. Cross-cultural research is essential in
      enabling us to determine whether similar trends exist across cultures.

PMID- 11294541
TI  - The effect of neurocranial surgery on basicranial morphology in isolated sagittal
      craniosynostosis.
AB  - OBJECTIVE: Isolated sagittal craniosynostosis produces a scaphocephalic
      neurocranium associated with abnormal basicranial morphology, providing
      additional evidence of the developmental relationship of the neurocranium and
      basicranium. Corrective surgical procedures vary, but the immediate impact of the
      surgical procedure is restricted to the neurocranium. This study addresses the
      secondary effects of neurocranial surgery on the cranial base. DESIGN: Three
      dimensional (3-D) computed tomography (CT) scans were obtained for preoperative
      (n = 25) and postoperative (n = 12) patients with isolated sagittal synostosis.
      Landmark data from 14 landmarks on and around the cranial base were collected
      from 3-D CT reconstructions and analyzed using Euclidean distance matrix
      analysis. Subsamples of age-matched patients were used to identify basicranial
      differences in pre- and postoperative patients and to compare postoperative
      growth patterns identified in longitudinal data with preoperative growth patterns
      characterized in cross-sectional data. RESULTS: Statistically significant
      differences (p < or = 0.10) were found in the morphology of the cranial base in
      preoperative and postoperative patients. The relative positions of the landmarks
      nasion, right asterion, and left asterion are similar in preoperative and
      postoperative patients. However, the position of these landmarks relative to the
      cranial base is different in the two groups, being positioned relatively more
      anteriorly in postoperative patients. In addition, we found that the cranial base
      angle, on average, neither increases nor decreases in the first postoperative
      year. These morphological differences are associated with divergent growth
      trajectories in the operated and unoperated cranial base. CONCLUSION: Regardless
      of specific procedure, neurocranial surgery in sagittal synostosis patients
      affects growth patterns of the cranial base. The lack of change in the
      postoperative cranial base angle suggests that neurocranial surgery alleviates
      the occipital rotation and decreased cranial base angle described in the sagittal
      synostosis basicranium.

PMID- 11294542
TI  - Skeletal advancement for the treatment of obstructive sleep apnea in children.
AB  - OBJECTIVE: Maxillomandibular advancement is curative for some adult patients with
      obstructive sleep apnea (OSA). Little is known, however, about the efficacy of
      this treatment in children. The purpose of this retrospective analysis is to
      assess the clinical outcomes of children with medically refractory OSA who were
      treated with a variety of procedures to advance the maxillofacial skeleton.
      METHODS: The records of eight children with OSA (five boys and three girls; mean
      age, 8.6 years; range, 2 to 17 years) were reviewed. Six children had
      identifiable syndromes associated with micrognathia, one child had mandibular
      ankylosis, and one child was nonsyndromic. In five of the children, conventional
      medical and surgical treatment of OSA had failed; therefore, these children were
      considered tracheostomy candidates. The remaining three children had had
      tracheostomies placed in infancy. Specific signs and symptoms with regard to each
      patient's OSA were identified and recorded. Bronchoscopy was performed
      preoperatively to evaluate the airway and localize the site of obstruction and
      again postoperatively if the patient's signs and symptoms recurred. Oxygen
      saturation and sleep patterns were monitored overnight in the five patients
      without tracheostomies, revealing a mean apnea index of 25.3 (range, 2.0 to 60.0)
      and mean lowest desaturation of 73% (range, 62% to 77%). All patients underwent a
      variety of skeletal procedures to advance the mandible, maxilla, and/or chin.
      OUTCOME MEASURES: Criteria for success after treatment were twofold: (1)
      decannulation and (2) cessation or improvement in symptoms facilitating avoidance
      of tracheostomy. Criteria for failure, likewise, were (1) inability to
      decannulate and (2) recurrence or nonimprovement in symptoms necessitating
      tracheostomy. RESULTS: To date, with a mean follow-up time of 7.2 years (range,
      19 months to 19 years), the treatment of four of the eight children in our
      population can be considered a success. Two of the three children with previously
      placed tracheostomies were able to be decannulated within days of surgery and
      experienced no further signs or symptoms of OSA. Two other children experienced
      complete cessation of clinical signs and symptoms and elimination of previous
      oxygen requirements. Of the four patients in whom treatment failed, three had
      transient improvement (mean, 6 months) and, despite skeletal stability,
      eventually experienced relapse of symptoms: one patient with Down syndrome and
      tracheobronchomalacia required subsequent tracheostomy; the second had a central
      obstructive component and underwent a ventriculoperitoneal shunt for treatment of
      a Chiara I malformation; and the third experienced relapse of symptoms due to
      lack of mandibular growth. The fourth child could not be decannulated because of
      accompanying tracheal and laryngeal malacia. CONCLUSIONS: Skeletal advancement
      can be an effective treatment for medically refractory OSA in children. Success,
      however, is dependent not only on skeletal position but also on neuromuscular
      adaptation. Bronchoscopy is the most valuable diagnostic and predictive tool.

PMID- 11294543
TI  - Mandibular bone graft material for reconstruction of alveolar cleft defects: long
      term results.
AB  - OBJECTIVE: To analyze the long-term effect of mandibular bone as donor material
      in bone grafting of the alveolar process defect in patients with unilateral cleft
      lip and palate (UCLP), compared with iliac crest cancellous bone. METHOD: During
      a 7-year period, 101 UCLP patients were bone grafted, 57 cases with iliac crest
      cancellous bone and 44 with mandibular symphyseal bone. The long-term results
      with an observation time of more than 4 years were analyzed with respect to
      marginal bone level and dental and gingival condition in the grafted area.
      Complications were recorded. RESULTS: The bone level in the grafted area was
      satisfactory in both groups. Impaction of cleft-side canines was found in 35% of
      the patients in both groups. Patients with agenesis of the cleft side lateral
      incisor had significantly more impacted canines, compared with patients with a
      cleft-side lateral situated in the lesser maxillary segment, probably due to the
      fact that the lateral incisors help in guiding the canine down through the
      grafted area. The number of complications was scarce, although both groups
      demonstrated some gingival retraction with a longer crown length at the cleft
      side central incisor. CONCLUSION: The findings of this study have changed our
      strategy in bone grafting. Timing of orthodontic treatment and bone grafting has
      been more varied depending on the position and presence of teeth in the cleft
      area. Bone grafting of the alveolar process is not just a local treatment of a
      bony defect, but in respect to the burden of treatment, bone grafting of the
      alveolar process has to be planned in accordance with orthodontic treatment and
      maxillofacial growth.

PMID- 11294544
TI  - Characteristic forms of the upper part of the oral cavity in newborns with
      isolated cleft palate.
AB  - OBJECTIVE: To determine the functional and morphological compensation of the lack
      of integrity in the upper part of the oral cavity in newborns with isolated cleft
      palate. Integrity of the upper part of the oral cavity is required for the
      effective pumping of amniotic fluid, the essential mode of nutrition in
      intrauterine life. The adaptation could be seen immediately after birth.
      MATERIALS: Plaster casts of the upper part of the oral cavity in 60 newborns with
      isolated cleft palate of various extent and plaster casts of the upper part of
      the oral cavity in 27 newborns without cleft were used. A number of surface
      points were identified and used for a trigonometric morphological analysis.
      RESULTS: The parameters of the upper part of the oral cavity in four groups of
      newborns with various extent of isolated cleft palate were compared with newborns
      without cleft palate. The results indicate a shift of the functional oral cavity
      into the nasal cavity and the pharynx, depending on the extent of the cleft.
      CONCLUSION: The pumping activity of the tongue forms the upper part of the oral
      cavity and consequently the tongue moves into the nasal cavity and pharynx,
      depending on the extent of the cleft. In this way, effective pumping of amniotic
      fluid is possible despite the cleft. This is of vital importance for the fetus
      during intrauterine life. A poorly passable or even unpassable respiratory way is
      only of secondary importance during that time.

PMID- 11294545
TI  - Clinical experience with infants with Robin sequence: a prospective study.
AB  - OBJECTIVE: To study the clinical course of patients with Robin sequence (RS)
      during the first 6 months of life. DESIGN: A longitudinal prospective study of
      children with RS. SETTING: Hospital de Reabilitacao de Anomalias Craniofaciais,
      Universidade de Sao Paulo, Bauru-SP, Brazil, 1997 and 1998. PATIENTS: Sixty-two
      children were studied from hospital admission to 6 months of age. Thirty-three
      (53.2%) presented with probable isolated RS (PIRS), 25 (40.3%) presented with
      syndromes or other malformations associated with RS, and 4 (6.5%) presented with
      RS with neurological involvement. INTERVENTIONS: The type of respiratory tract
      obstruction was defined by nasopharyngoscopy. The patients with type 1 and type 2
      obstruction underwent nasopharyngeal intubation (NPI), and glossopexy was
      indicated in patients with type 1 obstruction who did not show clinical
      improvement with this procedure. Tracheostomy was indicated in patients with type
      2 obstruction who did not show a good course after NPI, in patients with type 1
      obstruction who did not show good course after glossopexy, and in patients with
      type 3 and type 4 obstruction. RESULTS: Prone position treatment (PPT) or NPI was
      the definitive treatment in 25 cases (75.8%) of PIRS and in 13 cases (52%) of
      syndromes or other malformations. Among the children with type 1 obstruction, 24
      (51.1%) were submitted exclusively to PPT and 12 (25.5%) to NPI. With the type 2
      groups, only one (12.5%) received PPT, and three (37.5%) were treated exclusively
      with NPI. All 15 infants treated exclusively with NPI (24.4%) presented with good
      weight, length, and neuromotor development. CONCLUSIONS: Most patients with PIRS
      and type 1 obstruction improved without surgical intervention. NPI should be the
      initial treatment in all patients with RS with type 1 and type 2 obstruction who
      present with important respiratory and feeding difficulties.

PMID- 11294547
TI  - Gastroesophageal reflux in Pierre Robin sequence--early surgical treatment.

PMID- 11294546
TI  - Changes in speech following unilateral mandibular distraction osteogenesis in
      patients with hemifacial microsomia.
AB  - OBJECTIVE: The purpose of this study was to describe changes in articulation,
      resonance, and velopharyngeal function following mandibular distraction
      osteogenesis. DESIGN: This is a descriptive, post hoc study comparing the
      performance of patients on measures of articulation, resonance, and
      velopharyngeal function before and after mandibular distraction. SETTING: The
      data were collected at a tertiary health care center located in Chicago.
      PATIENTS: The clinical data from preoperative and postoperative evaluations of
      seven mandibular distraction patients were used. OUTCOME MEASURES: The outcome
      measures were number of articulation errors, severity of hypernasality and
      audible nasal emission, and velopharyngeal orifice size as estimated using the
      pressure-flow technique. RESULTS: Immediately after distraction, 28% (2/7)
      experienced a temporary deterioration in articulation and 42% (3/7) experienced a
      deterioration in nasal resonance. But by the long-term follow-up evaluation, all
      had returned to their preoperative levels. Pressure-flow test results generally
      support the perceptual findings. CONCLUSIONS: Patients being considered for
      mandibular distraction surgery should receive preoperative and postoperative
      speech evaluations and be counseled about risks for changes in their speech
      following surgery.

PMID- 11294548
TI  - An electropalatographic investigation of middorsum palatal stops in an adult with
      repaired cleft palate.
AB  - OBJECTIVE: Middorsum palatal stops are compensatory articulations that occur
      relatively frequently in cleft palate speech. This study used
      electropalatographic (EPG) and acoustic data to investigate /t/ and /k/ targets
      produced as middorsum palatal stops ([c]) by an adult with an articulation
      disorder associated with a repaired cleft palate. RESULTS: Two novel observations
      were made from the instrumental data. First, although /t/ and /k/ targets were
      judged by phonetically trained listeners as homophonous (i.e., both produced as
      [c]), the EPG data revealed that the place of articulation for the [c] produced
      for /t/ was more anterior than the place of articulation for the [c] produced for
      /k/. Second, production of palatal stops involved lateral release followed by a
      variable period of lateral friction. Measurements made from the instrumental data
      quantified the temporal extent of lateral friction during the aspiration period.
      CONCLUSIONS: These observations merit further systematic investigation in cleft
      palate speech, and the procedures reported in this study are considered
      appropriate for such future research.

PMID- 11294549
TI  - Changes in respiratory function during a wilderness multisport endurance
      competition.
AB  - OBJECTIVE: To document the changes in respiratory function seen in competitors
      during a typical wilderness multisport endurance event. METHODS: A prospective
      observational cohort study measuring forced expiratory volume in 1 second (FEV1)
      and forced vital capacity (FVC) at baseline, midrace, and end of race in
      competitors in a 105-km ski/run/cycle/paddle race held midwinter in the mountains
      of Victoria, Australia. RESULTS: Twenty-five adult subjects (22 men) between 20
      and 42 years of age were studied. The mean decline in FEV1 was 15.1% (95% CI 10.3
      19.8) and for FVC was 13.0% (95% CI 8.1-17.9). Fourteen (56%) of the 25 subjects
      had a >10% decline in FEV1 and FVC, and 7 (28%) of the 25 subjects had a >20%
      decline. In 9 control subjects, aged between 21 and 55 years, there was no
      significant change in FEV1 or FVC from prerace to end of race. CONCLUSIONS:
      Significant declines in FEV1 and FVC are common during wilderness multisport
      endurance events. The focus of future research should be the etiology, which as
      yet remains speculative.

PMID- 11294550
TI  - Venomous snake husbandry in Thailand.
AB  - A captive breeding program for venomous Thai snakes was established at the Queen
      Saovabha Memorial Institute at Bangkok, Thailand. This was necessary to secure a
      stable, healthy, and species-confirmed source of snake venom for antivenom
      production. In 1994, wild-caught specimens were collected, sexed, quarantined,
      and housed appropriately. All data in this report, with the exclusion of Table 6,
      were collected from 1994 to 1997. Two species were bred successfully in captivity
      to date during this study period. Although captive breeding has not yet been
      achieved with all species and subspecies, our early success was encouraging.

PMID- 11294551
TI  - Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with
      chronic mountain sickness.
AB  - BACKGROUND: Individuals with chronic mountain sickness (CMS) show severe
      hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The
      pathophysiologic mechanisms of CMS are still not completely understood. METHODS:
      We determined plasma atrial natriuretic peptide (ANP), red cell 2,3
      diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe
      blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han
      Chinese men of similar age, height, and weight who had been living at 4300 m on
      the Tibetan plateau of Qinghai Province, China, for approximately 14 years.
      RESULTS: A significantly higher level of ANP was found in the CMS patients
      compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P <
      .01), and the levels of ANP correlated positively with the hemoglobin
      concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were
      significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs
      4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients
      were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS
      patients had significantly higher PaCO2 levels, lower pH values, lower PaO2
      levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared
      to the non-CMS subjects. CONCLUSIONS: These findings suggest that overproduction
      of ANP and 2,3-DPG at high altitudes may play an important role in the
      pathophysiology of chronic mountain sickness.

PMID- 11294552
TI  - Prehospital treatment of hypothermia.
AB  - This article considers several issues regarding cold stress, development of
      hypothermia, and prehospital care of the hypothermic patient. Advice is given on
      the use of clinical impressions and functional characteristics to determine the
      level of hypothermia. Response to cold water immersion is characterized as short
      term (cold shock response), midterm (loss of performance), and long-term
      (development of hypothermia). Circum-rescue collapse is the dramatic worsening
      condition of the patient just before, during, or after rescue from cold stress.
      After rescue, the treatment priorities are to arrest the fall in core
      temperature, establish a steady, safe rewarming rate while maintaining the
      stability of the cardiorespiratory system, and provide sufficient physiological
      support.

PMID- 11294553
TI  - Body cooling and response to heat--a commentary.

PMID- 11294554
TI  - Body cooling and response to heat. 1961.

PMID- 11294555
TI  - Poison oak dermatitis.

PMID- 11294556
TI  - How to use textbooks, handouts, and visual aids.

PMID- 11294557
TI  - Cerebral edema in the Himalayas: too high, too fast!

PMID- 11294558
TI  - Medical tourism.

PMID- 11294559
TI  - More "medical tourists" needed, not fewer.

PMID- 11294560
TI  - A personal account of high-altitude pulmonary edema.

PMID- 11294561
TI  - Alterations in autonomic nervous control of heart rate among tourists at 2700 and
      3700 m above sea level.
AB  - OBJECTIVES: Many travelers who are not specially trained for activities at high
      altitude are at risk of physical problems, including cardiovascular disorders,
      when exposed to high-altitude environments. In the present study, we investigated
      how actual acute exposure to altitudes of 2700 and 3700 m affected the autonomic
      nervous control of heart rate in untrained office workers. METHODS: Physiological
      parameters (heart rate, respiratory rate, arterial blood oxygen saturation, and
      end-expiratory carbon dioxide tension) were measured at sea level, 2700 m, and
      3700 m. The power of heart rate variability was quantified by determining the
      areas of the spectrum in 2 component widths: low frequency (LF; 0.04-0.15 Hz) and
      high frequency (HF; 0.15-0.5 Hz). The ratio of LF power to HF power (LF:HF),
      which is considered to be an index of cardiac sympathetic tone, was also
      assessed. RESULTS: Both HF and LF heart rate variability decreased according to
      the elevation of altitude. High- and low-frequency powers at 3700 m were
      significantly lower than those at sea level (P < .01 for HF, P < .05 for LF). The
      LF:HF ratio at 2700 m was not significantly different from that at sea level.
      However, it was significantly increased at 3700 m (P < .01). CONCLUSIONS: At 2700
      and 3700 m, the activity of the autonomic nervous system measured by heart rate
      variability was decreased in untrained office workers. The sympathetic nervous
      system was dominant to the parasympathetic at 3700 m. These alterations in the
      autonomic nervous system might play some role in physical fitness at high
      altitudes.

PMID- 11294562
TI  - Hepatitis B surface antigen- and tetanus toxoid-specific clonal expansion of CD4+
      cells in vitro determined by TCRBV CDR3 length and nucleotide sequence.
AB  - We demonstrate activation of primary human TCRBV-specific CD4+ cells in vitro
      towards hepatitis B surface antigen (HBsAg) and tetanus toxoid (TT) without the
      use of cell lines, clones or added cytokines. By multiplex PCR analysis and
      spectratyping, antigen-activated cells exhibited clonal T cell receptor expansion
      within specific and limited TCRBV families. The expanded CD4+ T cells were
      CD45RO. Three of four unrelated HBsAg responders showed CD4+ expansion within the
      TCRBV16 family. The response comprised predominantly single CDR3 sequences in all
      three donors and was completely monoclonal in one of them. However, the CDR3
      lengths and sequences differed among the responders. Clonality induced by HBsAg
      in TCRBV16 was specific, reproducible and distinct from that induced by TT in
      terms of sequence, nucleotide addition and diversity (BD) or junctional (BJ)
      element usage. Thus, for the first time, we show monoclonal or oligoclonal
      expansion of primary human CD4- peripheral blood mononuclear cells (PBMC) in
      vitro in response to nominal protein antigen without manipulations utilizing
      exogenous IL-2. The ability to induce monoclonal/ oligoclonal responses to HBsAg
      now permits motif identification studies for determining the T cell role in
      nonresponsiveness to the HBsAg vaccine.

PMID- 11294563
TI  - Linkage analysis of the 5q31-33 candidate region for asthma in 240 UK families.
AB  - Atopy and asthma are complex genetic diseases resulting from the interactions of
      a number of genetic and environmental factors. We had previously reported allelic
      association between the IL9 marker on chromosome 5q31-33 and atopy. In order to
      further investigate the role of susceptibility genes on 5q31-33 in the
      development of atopy and asthma we have studied 240 UK families comprising 131
      families selected at random, 60 multiplex families with affected sib pairs, and
      49 single proband nuclear families. Polymorphic markers on 5q31-33 were genotyped
      and both single and multipoint linkage analysis was undertaken using the BETA
      program. We have used both affection status and quantitative scores for atopy and
      asthma for phenotypic variables, combining data into scores for asthma and atopy.
      The strongest suggestion of linkage using multipoint analysis was centred around
      D5S410 with a maximum Lod of 1.946 at location 171.3 cM and a standard error of
      3.3 for the asthma quantitative score. There was no evidence of linkage with
      atopy, the atopy quantitative score or total serum IgE.

PMID- 11294564
TI  - IL-10 promoter polymorphisms influence tumour development in cutaneous malignant
      melanoma.
AB  - Cutaneous malignant melanoma (CMM) is the most serious cutaneous malignancy. CMM
      patients often develop an immune response to their tumours. Conflicting evidence
      suggests that IL-10 may contribute to tumour escape from the immune response, but
      may also have an anti-tumour effect. To distinguish between these models and to
      determine whether genotypes associated with differential IL-10 expression confer
      susceptibility to and/or influence prognosis in CMM, 165 CMM patients and 158
      controls were genotyped for IL-10 promoter SNPs by ARMS-PCR. The IL-10--1082 AA
      low expression genotype was increased in incidence among CMM patients (P = 0.04).
      In addition, IL-10 genotypes showed significant associations with three of four
      prognostic indicators examined; IL-10--1082 GG (P = 0.02) and -1082, -819 and 
      592 compound high expression (P = 0.03) genotypes were associated with horizontal
      (non-invasive) tumour growth; IL-10--1082 AA low expression genotype was
      associated with more advanced (Stage II-IV) disease (P = 0.04); finally, the IL
      10--1082 AA (P = 0.005) and compound low expression (P = 0.009) genotypes were
      significantly increased in frequency among patients with thicker primary Vertical
      growth phase tumours. These results indicate that genotypes associated with high
      levels of IL-10 expression in vitro are protective in CMM, while low expression
      genotypes are a risk factor for more advanced/poorer prognosis disease and may
      confer susceptibility to CMM. Although the influence of IL-10 on melanoma
      development is likely to be complex, these results support recent findings that
      IL-10 has an anti-tumour effect in CMM, possibly via inhibition of angiogenesis.

PMID- 11294565
TI  - Genotyping TAP2 variants in North American Caucasians, Brazilians, and Africans.
AB  - The protein forms of transporter associated with antigen processing, subunit 2
      (TAP2), differ either by amino acid substitutions (Thr374Ala, Ile379Val,
      Ile467Val, Thr565Ala, Val577Met, Cys651Arg, and Ala665Thr) or by a truncation
      (Gln687Stop) of 17 amino acid residues at the C-terminus. Nonsynonymous single
      nucleotide polymorphisms (N-SNPs) causing these amino acid variations except
      577Val were detected in genomic DNA samples from North American Caucasians (n =
      76), Brazilians (n = 148), Rwandans (n = 285), and Zambians (n = 117). Exclusive
      (100%) and nearly exclusive (>95%) linkage disequilibrium was seen with a number
      of N-SNPs. The average heterozygosity at any given dimorphic site ranged from
      7.3% to 44.6%, and at least four N-SNPs showed clear population specificity. N
      SNP combinations alone led to the identification of 16 relatively common alleles,
      which appeared to form at least three lineages. Further analyses of 101 cDNA
      samples from Brazilians detected nine expressed TAP2 alleles, four of which
      matched the official assignments. Genetic complexity at the TAP2 locus was
      further enhanced by two out of five synonymous SNPs (S-SNPs), especially the
      GGT386GGG (Gly) that had similar heterozygosity rates in Caucasians (28.9%),
      Rwandans (33.3%), and Zambians (33.3%). Overall, distribution of both synonymous
      and nonsynonymous SNPs in the various ethnic groups examined here conformed well
      to the Hardy-Weinberg equilibrium, and between 57.9% and 77.0% of subjects in
      each ethnic group were heterozygous with two TAP2 alleles predicted to differ by
      at least one amino acid residue. Such complexity of TAP2 polymorphisms, in the
      form of SNPs as well as alleles, is likely to complicate the analyses of disease
      associations and haplotype structures in the HLA class II region.

PMID- 11294566
TI  - HLA alleles in relation to specific immunity to liver stage antigen-1 from
      plasmodium falciparum in Gabon.
AB  - Cellular responses to synthetic peptides from the Liver Stage Antigen-1 (LSA-1)
      from Plasmodium falciparum were determined in 229 Gabonese children. HLA class I
      and II typing (by PCR-SSP and -RFLP, respectively) revealed that HLA-A*19, -B*17
      (and -B*70), -DRB1*05, -DQA1*0102, -DQB1*0602 and -DPB1*0402 were the most
      frequent types or alleles at each locus. The DQB1*0201 and DQB1*0301 alleles were
      present at a higher frequency among IL-6 and IFN-gamma responders to the LSA-Rep
      and LSA-CTL peptides, respectively, and a higher proportion of these responders
      carried A*19 or B*53. The DRB1*06 type was positively related to the IL-10
      production in response to the LSA-CTL peptide, and responders presented mainly
      A*2. The specificity A*10 was negatively associated with the cellular response to
      the LSA-J peptide. These results suggest a degree of genetic regulation of
      specific immune responses by HLA-A, operating at the pre-erythrocytic stage of
      development of P. falciparum in this Central African population.

PMID- 11294567
TI  - A polymorphic variant of the gene coding desmoglein 1, the target autoantigen of
      pemphigus foliaceus, is associated with the disease.
AB  - Two polymorphic markers were identified on the desmoglein 1 gene which encodes
      the autoantigen targeted by pathogenic antibodies in pemphigus foliaceus (PF), a
      cutaneous autoimmune blistering disease. The first marker, made of a variant
      haplotype of five mis-sense mutations located on the part of the gene encoding
      the fourth and fifth extracellular domains of the protein, is not associated with
      the disease. The second marker consists of a single silent T to C transition at
      position 809 and was found to be significantly more frequent (P = 0.015) in
      Caucasian PF patients (n = 36) than in controls (n = 98). Thus, pemphigus
      foliaceus constitutes another example of autoimmune disease in which the
      autoantigen polymorphism contributes to disease susceptibility.

PMID- 11294568
TI  - Association of single nucleotide polymorphisms in the interleukin-4 gene and
      interleukin-4 receptor gene with Crohn's disease in a British population.
AB  - Interleukin-4 (IL-4) is an important cytokine in mucosal immunity and plays a
      critical role in the development of colitis in T-alpha cell receptor mutant mice.
      Functionally significant polymorphisms have been described in the genes encoding
      IL-4 and IL-4 receptor. To examine the role of these polymorphisms in disease
      susceptibility 98 patients with ulcerative colitis, 86 patients with Crohn's
      disease and 321 healthy controls were genotyped for polymorphisms at position -34
      in the IL-4 gene and codon 576 in the IL-4 receptor gene. Thirty-two percent of
      patients with Crohn's disease carried one or two copies of the variant allele for
      IL-4 compared with 16% of the controls (P = 0.002). Forty-one percent of patients
      with Crohn's disease carried one or two copies of the variant IL-4 receptor
      allele compared with 31% of the controls (P = 0.09). Fifteen percent of patients
      with Crohn's disease carried combination of both (IL-4 and IL-4 receptor) variant
      alleles compared with 4% of the controls (P = 0.005). Association with alleles
      resulting in high IL-4 transcription and enhanced signalling activity suggests
      that IL-4 may have a role in the pathogenesis of Crohn's disease.

PMID- 11294569
TI  - Rat tapasin: cDNA cloning and identification as a component of the class I MHC
      assembly complex.
AB  - During the assembly of major histocompatibility complex (MHC) class I molecules
      transient associations are formed with the endoplasmic reticulum resident
      chaperones calnexin and calreticulin, ERp57 oxidoreductase, and also with
      tapasin, the latter mediating binding of the class I molecules to the transporter
      associated with antigen processing (TAP). We report here the isolation of a cDNA
      encoding rat tapasin from a DA (RT1av1) library. The cDNA encodes a proline-rich
      (11.3%) polypeptide of 464 residues with a potential ER-retention KK motif at its
      COOH-terminus, and a predicted molecular mass of 48 kDa. Matrix-assisted laser
      desorption ionisation (MALDI) mass spectrometry of peptides derived from in-gel
      tryptic digestion of a TAP-associated protein match regions of the predicted
      translation product. A species of the correct molecular mass and predicted pl was
      also identified in association with radiolabelled immunoprecipitates of the rat
      TAP complex analysed by two-dimensional gel electrophoresis. This confirms rat
      tapasin as a component of the rat MHC class I assembly complex.

PMID- 11294571
TI  - LPS-hyporesponsiveness of mnd mice is associated with a mutation in Toll-like
      receptor 4.
AB  - Toll-like receptors (Tlrs) are transmembrane proteins that have recently been
      shown to play a critical role in the innate immune recognition of microbial
      constituents. Among this family, Tlr4 is a crucial signal transducer for
      lipopolysaccharide (LPS), the major component of the Gram-negative bacteria outer
      cell membrane. In this paper, we report that C57BL/6.KB2-mnd mice, a model of
      neuronal ceroid lipofuscinosis, do not respond to LPS. This defect is associated
      with a spontaneous mutation in Tlr4 consisting of a large insertion within exon 2
      predicting a frameshift mutation and a truncated protein.

PMID- 11294570
TI  - Cloning and characterization of TNKL, a member of tankyrase gene family.
AB  - By serological screening of a breast tumor cDNA library we have identified a
      novel human gene, tnkl, encoding an ankyrin-related protein with a high degree of
      similarity to tankyrase, the poly(ADP-ribose)polymerase associated with human
      telomeres (Smith et al, Science 282: 1484). The tnkl gene maps to chromosome 10,
      while the tnks gene encoding tankyrase is located on chromosome 8. The predicted
      1166-aa protein product of the tnkl gene is 78% identical to human tankyrase and
      62% to a putative D. melanogaster protein. Since the proteins have essentially
      identical domain structures, the corresponding genes form a distinct gene family.
      The possible link between TNKL and cancer justifies its further functional
      analysis.

PMID- 11294572
TI  - Change of hypervariable region proteins of hepatitis C virus E2 in two infants.
AB  - Two infants vertically infected with hepatitis C virus (HCV) were followed-up
      from 3 or 4 months to 2.5 years of age. We analyzed five complementary DNA (cDNA)
      clones from each patient and compared the genetic drift of the HCV E2 gene
      hypervariable region (HVR) between the two infants and between the infants and
      their mothers within the two families. The HCV strains initially detected in
      infant 1 were identical to those found in her mother, while the HCV strains
      initially detected in infant 2 were very different from those of her mother. The
      mutation rate of HVR-1 proteins was higher in mother 1 than in mother 2, but was
      1.6 to 2-fold higher in infant 2 than in infant 1 during the follow-up period.
      Serum ALT levels or serum HCV-core protein activity did not correlate with the
      mutation rates of HVR-1 proteins in either infant. However, the mutation rate of
      HVR-1 proteins significantly increased from 6 months of age in both infants, with
      concomitantly increased serum HCV antibody (anti-HCV) levels.

PMID- 11294573
TI  - Small, dense low density lipoprotein (LDL) and the insulin resistance syndrome
      (IRS).
AB  - The preponderance of small, dense LDL particles has been termed a conditional
      cardiovascular risk factor, indicating that data derived from experimental,
      clinical and intervention studies suggest a strong relation of LDL size and
      cardiovascular (atherosclerotic) disease (77). However, the lack of randomized,
      controlled trials showing a beneficial effect of increasing LDL size on
      cardiovascular disease independent of other known risk factors (including
      hypertriglyceridemia) precludes the inclusion of small, dense LDL into the
      category of "causal" risk factors. Accordingly, as of today, LDL particle size
      can not (yet) be considered a primary target of risk factor intervention, and
      neither can its routine assessment for clinical purposes be recommended. Numerous
      studies have unanimously shown that components of the IRS, including insulin
      resistance itself, constitute major environmental determinants of LDL size.
      Therefore, therapies aiming at improving insulin resistance have the potential to
      modify small, dense LDL towards larger, more buoyant particles. Randomized
      controlled trials investigating the effect of these therapies not only on LDL
      size but also on clinical (cardiovascular) endpoints will be of particular
      interest.

PMID- 11294575
TI  - Rapid DNA typing of HLA-B27 allele by real-time PCR using lightcycler technology.
AB  - For clinical diagnostic routine we developed a fast DNA typing of HLA-B27 by PCR
      and real-time detection using LightCycler technology. The method combines the
      sensitivity and specificity of PCR with the swiftness of the LightCycler system.
      The amplification step was performed with a primer set coding for a region in the
      third exon common to B*2701 to B*2705. The PCR cycles were monitored continuously
      using the SYBR Green I dye. Beta-globin was used as an internal control. An
      analysis of 32 samples with one PCR run was completed within 40 minutes. After
      amplification a melting curve analysis permitted the accurate identification of
      the PCR amplicons. The mean melting temperatures (Tm) were 90.5 degrees C and
      87.3 degrees C, which are characteristic for HLA-B27 and beta-globin,
      respectively. A comparison of 300 samples which were typed for HLA-B27 with a
      conventional sequence-specific polymerase chain reaction (SSP-PCR) and with the
      new method demonstrated a perfect correlation (specificity 100%). In summary, the
      method described is fast, reliable, cost-effective and well adapted for routine
      laboratory testing.

PMID- 11294574
TI  - Performance of a conventional enzyme immunoassay for hepatitis C virus core
      antigen in the early phases of hepatitis C infection.
AB  - There are periods within the early phase of hepatitis C virus (HCV) infection in
      which the anti-HCV antibody test is unable to confirm HCV viremia. To reduce the
      risk of transmitting HCV through transfusions, we developed a simple and highly
      sensitive enzyme immunoassay (EIA) which detects the core antigen of HCV
      (HCVcAg). This assay employed a conventional colorimetric EIA system, and was
      based on a two-step sandwich assay, using a 96- well microplate. The
      reproducibility of the results was very high. When the cutoff values were set to
      30 fmol of recombinant HCVcAg/L, as determined by the distribution of healthy
      subject sera (n=223), 99.6% of healthy subject sera and 100% of hepatitis B
      patient sera (n=50) were negative for HCVcAg. The clinical performance of this
      EIA was examined using 14 commercially available seroconversion panels. In every
      panel, HCVcAg could be detected at points preceding the seroconversion of anti
      HCV antibodies. The points at which HCVcAg was detected were the same as those at
      which it was detected by an AMPLICOR HCV Monitor test. The EIA's window period
      for detecting the HCVcAg in all panels was on average 26 days shorter than that
      of the anti-HCV antibody test. In three panels where the first sample is negative
      for HCV RNA, the window period was shortened 50 days by this EIA for HCVcAg.
      There was a positive correlation between the concentration of HCVcAg and HCV RNA
      in anti-HCV antibody negative specimens. This assay was simpler to perform than
      assays based on gene amplification technology for the detection of HCV RNA, and
      the window period was shortened to that of the AMPLICOR HCV Monitor test. Thus,
      the EIA for HCVcAg would be useful in screening seroconverting donors and could
      reduce the residual risk of secondary HCV infections through transfusions.

PMID- 11294576
TI  - Contribution of new techniques for the diagnosis of congenital toxoplasmosis.
AB  - Congenital toxoplasmosis is still a concern, particularly in France, where the
      seroprevalence is high. For an efficient prevention program, reliable techniques
      are necessary. During the past ten years, biological advances have been made to
      improve the performance of antenatal diagnosis as well as the postnatal detection
      of infected neonates. In this review we will touch on three main points: 1) the
      dating of seroconversion during the course of pregnancy, 2) the value of
      antenatal diagnosis, 3) the new modalities for postnatal serological follow-up of
      newborns.

PMID- 11294577
TI  - Intestinal permeability tests in coeliac disease.
AB  - Intestinal permeability tests have been used to screen for a wide range of small
      intestinal diseases, including coeliac disease and enteric infections. Several
      probe molecules have been used to investigate intestinal permeability including
      monosaccharides, disaccharides, 51Cr-EDTA and polyethyleneglycol. While many
      factors may affect intestinal permeability tests, the use of two probe molecules,
      for example, lactulose and mannitol, and the expression of the result as a ratio
      minimises the effects of these extraneous factors. Rendering the test solution
      hyperosmolar was also found to increase the sensitivity of the test in detecting
      coeliac disease. Intestinal permeability is characteristically elevated in
      untreated coeliac disease, with a sensitivity of up to 96% for the dual sugar
      techniques. The reason for this is a consistent increase in the absorption of
      lactulose (via the paracellular route) due to increased "leakiness" of the
      intestine and a reduction in the absorption of mannitol (via the transcellular
      route) due to a reduction in surface area as a result of villous atrophy. The
      intestinal permeability test allows subjects to be selected for jejunal biopsy in
      whom the clinical features are compatible with coeliac disease and in timing a
      follow-up biopsy. It has been postulated that raised intestinal permeability may
      be involved in the pathogenesis of coeliac disease. Recently, serum measurements
      of the probe molecules may have a valuable role, particularly in paediatric
      patients. Sucrose permeability has also been proposed as an accurate marker of
      adult coeliac disease and shows promise as a noninvasive test.

PMID- 11294578
TI  - The optimal treatment of venous thrombosis: current status and future
      perspectives.
AB  - Acute deep venous thrombosis (DVT) of the lower extremities is a serious and
      potentially fatal disorder, which often complicates the course of hospitalized
      patients but may also affect ambulatory and otherwise healthy people. Venous
      thrombosis is uncommon in young individuals and becomes more frequent with
      advancing age. The clinically important problems associated with venous
      thrombosis are death from pulmonary embolism, morbidity resulting from the acute
      event, recurrent venous thromboembolic events, the post-thrombotic syndrome, and
      the inconvenience and side-effects of investigations and treatment. The main
      objectives of treatment of DVT are prevention of (both fatal and nonfatal)
      pulmonary embolism and thrombus extension in the acute phase of the disease,
      prevention of recurrences of venous thromboembolism in the months following the
      acute episode, and prevention of late sequelae (post-thrombotic syndrome). These
      objectives are satisfactorily achieved with anticoagulant drugs (heparin and
      vitamin K antagonists), which therefore are the mainstays of DVT treatment. Other
      therapeutic options have a more limited application.

PMID- 11294579
TI  - Venous thromboembolism, fetal loss and preeclampsia in pregnant women with
      congenital thrombophilia.

PMID- 11294580
TI  - The effect of peat components on endocrine and immunological parameters and on
      trace elements--results of two pilot studies.
AB  - Peat and different peat preparations are successfully used in clinical therapies
      for different indications (as, for instance, in the field of gynecology). New
      studies show the biochemical effects of peat components which they have aside
      from their physical-thermal effects. This is of extraordinary interest with
      regard to the medical use of peat, because considerable concentrations of trace
      elements and heavy metals have been found in different kinds of peat. By means of
      atomic spectrometry it was investigated in 17 female patients with irritable
      bladder whether and how variations of the concentration of special trace elements
      and heavy metals (lead, cadmium, copper, manganese) could be measured within 24
      hour urine after vaginal peat-mush treatments had been applied serially.
      Additionally, the effect of peat-mush baths compared to the effect of water baths
      (n=6) - both of which were applied to 17 female patients with degenerative
      diseases - was examined with regard to their special endocrinological parameters.
      The results concerning safety did not show any changes of the concentration of
      the trace-elements or heavy metals within the 24-hour urine. These results can be
      explained by the chelating features of the peat components, which are the reason
      for the absorption of the trace elements. Examinations done to compare the
      effects of peat-mush baths and water baths have shown that peat components -
      independent from their thermal effects - are the reason for the occurrence of
      special effects. This applies in particular to the parameter soluble interleukin
      2-receptor. As regards estradiol, a significant increase could be measured after
      peat-mush baths had been applied to 17 postmenopausal female patients (n=11).
      Comparing these results with those of the group of patients treated with water
      baths, we noticed that the increase of estradiol was remarkably lower and not
      significant. The effect of the peat components is thought to be the reason for
      this.

PMID- 11294581
TI  - Laboratory diagnosis of cytomegalovirus (CMV) infections in immunodepressed
      patients, mainly in patients with AIDS.
AB  - There is a high prevalence of cytomegalovirus (CMV) infection in the general
      population. An important proportion of immunodepressed patients are latent
      carriers of the virus, and under these conditions, the lack of cellular immunity
      predisposes the patient to an active infection in which the virus is replicating.
      Consequences for the immunodepressed patients are widely variable, ranging from
      completely asymptomatic infections to life-threatening situations. An important
      characteristic of these infections is that they have no specific clinical
      symptoms and are often indistinguishable from other types of infection. As such,
      clinical diagnosis should be supported by laboratory tests. There are many
      diagnostic tests available, the choice of which one to use being made on the
      basis of clinician-defined objectives. The CMV immunological state of the patient
      should be ascertained in order to indicate the possibility of reactivation or the
      risk of primary infection. To this end, serological tests have proven to be the
      most useful. Laboratory tests also allow the rapid diagnosis of active CMV
      infections, for which rapid culture techniques (shell-vial) or viral antigen
      tests (antigenemia pp65) are more appropriate. Given that not all active
      infections present with symptoms, the most typical problem in clinical practice
      is to distinguish between symptoms and illnesses caused by CMV (CMV disease:
      CMVD), and other infectious or non-infectious entities. To clarify this
      situation, diagnostic histopathology and methods able to quantify the viral load
      (pp65 antigenemia and quantitative PCR) are of great use. The identification of
      patients who, during active infection, are at high risk of contracting CMVD in
      the near future, is a more complex challenge for the laboratory. Once again,
      tests that are able to quantify the viral load are the most appropriate for
      identifying those patients who should receive preventive antiviral treatment. In
      HIV-positive patients, CMVD tends to manifest itself as retinitis and involvement
      of the gastrointestinal tract. The principal risk factor in the development of
      CMVD in these patients is the degree of immunodepression, which appears almost
      exclusively in patients with a CD4+ lymphocyte count lower than 50/mm3 and when
      other opportunistic infections have occurred. The advent of oral ganciclovir has
      raised the possibility of long-term prophylactic treatment of CMVD, making the
      search for virological and immunological markers that identify these high-risk
      patients a priority. Techniques allowing the quantification of CMV viremia,
      namely pp65 antigenemia and quantitative PCR, have been most useful to this end.

PMID- 11294582
TI  - It's a jungle out there.

PMID- 11294583
TI  - Monovision LASIK procedures are progressively imprudent in presbyopic visual care
      of patients.

PMID- 11294584
TI  - Eye muscle physiotherapy.

PMID- 11294585
TI  - Cytomegalovirus retinitis.

PMID- 11294586
TI  - Traditional oriental medicine.

PMID- 11294587
TI  - What we think we know and the years ahead.

PMID- 11294588
TI  - Sensory eye dominance.
AB  - BACKGROUND: Sensory eye dominance is revealed in tasks like the Red Lens test and
      binocular rivalry. To understand its neural basis, we used a new protocol based
      on binocular rivalry to quantify its consequent interocular imbalance. Then we
      investigated whether the extent or sign of interocular imbalance is correlated
      with the difference in monocular contrast responses at threshold and
      suprathreshold and with the observer's motor eye dominance. METHODS: To evaluate
      sensory eye dominance, the stimulus intensity in each eye during rivalry was
      adjusted to achieve equal predominance. The difference in stimulus intensity
      constitutes the interocular imbalance. Standard procedures were used to measure
      monocular spatial contrast sensitivity, suprathreshold brightness judgment, and
      motor eye dominance. RESULTS: There was no positive correlation between
      interocular imbalance (sensory eye dominance) and motor eye dominance. No
      systematic correlation was found between interocular imbalance and monocular
      contrast sensitivities at 1 and 3 cycles/degree. Correlation coefficient between
      interocular imbalance and monocular suprathreshold brightness judgment was close
      to significant, suggesting that a difference in monocular brightness percept
      might (in part) account for interocular imbalance. But this explanation is only
      partial, since the difference in the monocular brightness percept was too small
      to account for the interocular imbalance. CONCLUSIONS: Interocular imbalance is a
      sensory eye dominance that cannot be equated with motor eye dominance. It
      manifests largely as a binocular phenomenon, which bears little relationship with
      the monocular neural mechanisms of contrast detection and brightness perception.

PMID- 11294589
TI  - Recurrent phlyctenular keratoconjunctivitis: a forme fruste manifestation of
      rosacea.
AB  - BACKGROUND: Phlyctenular keratoconjunctivitis represents a delayed type
      hypersensitivity response to a systemic antigen within the body. METHODS: We
      present a case of symptomatic, recurrent, phlyctenular keratoconjunctivitis in an
      8-year-old child. The patient's inflammation responded favorably to topical
      steroids at each episode, but no specific antigen could be identified.
      CONCLUSION: After observing the father's erythematous facial lesions, we
      attributed the child's ocular inflammation to rosacea (as a forme fruste
      manifestation) and treated her with systemic erythromycin. The symptoms were
      rapidly relieved and the disease process was arrested.

PMID- 11294591
TI  - Through the eyes of a child.

PMID- 11294590
TI  - Variability in doses obtained from a multi-dose ophthalmic solution: a potential
      source of error in the assessment of compliance.
AB  - BACKGROUND: Assessment of compliance with prescribed therapy is an important
      aspect of patient management that can be overlooked. Compliance with topical
      ophthalmic medications is frequently assessed without knowledge of doses obtained
      per bottle. METHOD: Thirty-three normal subjects who agreed to participate were
      asked to instill one drop of Refresh Tears in each eye twice daily until a 3-ml
      bottle was empty. Each subject was also asked to record the date and time of each
      drop instillation using a calendar log sheet. On enrollment, the subjects were
      required to demonstrate proper drop instillation technique. With the use of the
      log sheets, doses obtained and administrations missed by each subject were
      tabulated. The 'expected count' per bottle was determined by counting the drops
      in Refresh Tears under laboratory conditions. RESULTS: Of the 26 subjects, who
      completed the study, the mean (SD) number of doses reportedly obtained was 63.7
      +/- 17.1 (range = 26 to 110). The mean number of drops counted per bottle was
      63.5 +/- 1.0 (range = 62 to 65). CONCLUSIONS: The range of doses reportedly
      obtained per bottle was quite large. This variability could represent a
      significant source of error if patient compliance is assessed by how long a
      bottle lasts.

PMID- 11294592
TI  - Basic business entities for optometry practices.

PMID- 11294593
TI  - Motivating staff through recognition.

PMID- 11294594
TI  - A financial refresher.

PMID- 11294595
TI  - Reduced baroreceptor sensitivity during hypotension in ANP-knockout mice.
AB  - We studied baroreflex gain in inactin-anesthetized mice that had been genetically
      modified to be depleted of atrial natriuretic peptide (ANP -/-). Wild-type mice
      (ANP +/+) served as controls. ANP -/- mice had a significantly higher basal
      arterial blood pressure (ABP) than ANP +/+ mice [112+/-7 vs. 80+/-5 mmHg (mean +/
      SEM)]. Their basal heart rates were not different (491+/-13 vs. 446+/-19 bpm). A
      third group, composed of ANP +/+ mice only, was rendered acutely hypertensive by
      an intravenous infusion of arginine vasopressin acetate (0.3 pg bolus followed by
      0.3 pg/h) so as to serve as a control for the elevated ABP in the ANP -/- mice.
      Transient changes in ABP were caused by bolus injections of oxymetazoline
      hydrochloride (1.5-3 ng) or sodium nitroprusside (20-100 ng). Baroreflex gain was
      calculated as the ratio of the peak heart rate change that followed the peak
      change in mean ABP resulting from injection of oxymetazoline or nitroprusside.
      There were no significant differences among the groups in their responses to
      transient hypertension. On the other hand, the ANP -/- mice showed a
      significantly depressed tachycardic response to transient hypotension when
      compared with the other two groups. We conclude that the ANP -/- mice are unable
      to increase efferent sympathetic nervous activity adequately above the high basal
      activity that is a feature of this animal model.

PMID- 11294596
TI  - Effect of ischemia-reperfusion on the renal brush-border membrane sodium
      dependent phosphate cotransporter NaPi-2.
AB  - To understand the mechanisms underlying ischemia-reperfusion-induced renal
      proximal tubule damage, we analyzed the expression of the Na+-dependent phosphate
      (Na+/Pi) cotransporter NaPi-2 in brush border membranes (BBM) isolated from rats
      which had been subjected to 30 min renal ischemia and 60 min reperfusion. Na+/Pi
      cotransport activities of the BBM vesicles were also determined. Ischemia caused
      a significant decrease (about 40%, P < 0.05) in all forms of NaPi-2 in the BBM,
      despite a significant increase (31+/-3%, P < 0.05) in the Na+/Pi cotransport
      activity. After reperfusion, both NaPi-2 expression and Na+/Pi cotransport
      activity returned to control levels. In contrast with Na+/Pi cotransport,
      ischemia significantly decreased Na+-dependent glucose cotransport but did not
      affect Na+-dependent proline cotransport. Reperfusion caused further decreases in
      both Na+/glucose (by 60%) and Na+/proline (by 33%) cotransport. Levels of NaPi-2
      were more reduced in the BBM than in cortex homogenates, suggesting a
      relocalization of NaPi-2 as a result of ischemia. After reperfusion, NaPi-2
      levels returned to control values in both BBM and homogenates. These data
      indicate that the NaPi-2 protein and BBM Na+/Pi cotransport activity respond
      uniquely to reversible renal ischemia and reperfusion, and thus may play an
      important role in maintaining and restoring the structure and function of the
      proximal tubule.

PMID- 11294597
TI  - The role of K+ATP channels in the control of pre- and post-ischemic left
      ventricular developed pressure in septic rat hearts.
AB  - Myocardial function is impaired 24 h after the induction of sepsis, however,
      recovery of left ventricular (LV) function after 35 min of global ischemia is
      complete. The mechanisms by which this protection occurs are unknown. Ischemic
      preconditioning, another form of myocardial protection from ischemia/reperfusion
      (I/R) injury, has been shown to be modulated by ATP-sensitive potassium (K+ATP)
      channels. To investigate the role of K+ATP channels in the regulation of coronary
      flow (CF) and protection from I/R injury in septic rat hearts, we assessed the
      effects of the K+ATP channel antagonist glibenclamide (GLIB) and the agonist
      cromakalim (CROM) on pre- and post-ischemic CF and left ventricular developed
      pressure (LVDP). Although GLIB decreased pre-ischemic CF in both control and
      septic rat hearts, LVDP was unaffected. After I/R, CF was decreased in GLIB
      treated control and septic rat hearts and LVDP was more severely depressed in
      control rat hearts than in septic rat hearts. CROM increased pre-ischemic CF in
      the septic group although LVDP was unaltered in both groups. After I/R, control
      rat heart CF was depressed but LVDP completely recovered. Post-ischemic CF in
      septic rat hearts was elevated compared with vehicle-treated septic rat hearts,
      but the recovery of LVDP was not improved. These results suggest that K+ATP
      channels modulate CF in septic rat hearts, but do not mediate cardioprotection as
      observed in control rat hearts.

PMID- 11294598
TI  - Effect of trans-resveratrol on 7-benzyloxy-4-trifluoromethylcoumarin O
      dealkylation catalyzed by human recombinant CYP3A4 and CYP3A5.
AB  - Red wine concentrate has been reported to inhibit the catalytic activity of human
      recombinant cytochrome P450 (CYP) 3A4. Wine contains many polyphenolic compounds,
      including trans-resveratrol, which is also available commercially as a
      nutraceutical product. In the present study, we examined the in vitro effect of
      trans-resveratrol on human CYP3A catalytic activity by employing recombinant
      CYP3A4 and CYP3A5 as model enzymes and 7-benzyloxy-4-trifluoromethylcoumarin
      (BFC) as a CYP3A substrate. Trans-resveratrol inhibited BFC O-dealkylation
      catalyzed by CYP3A4 and CYP3A5 in a concentration-dependent manner. In each case,
      the inhibition was noncompetitive, as determined by Lineweaver-Burk and Dixon
      plots of the enzyme kinetic data. The apparent Ki values (mean +/- SEM) for the
      inhibition by trans-resveratrol of BFC O-dealkylation catalyzed by CYP3A4 and
      CYP3A5 were 10.2+/-1.1 microM and 14.7+/-0.3 microM, respectively. Preincubation
      of trans-resveratrol with NADPH and CYP3A4 or CYP3A5 for 10 or 15 min prior to
      initiation of substrate oxidation did not enhance the inhibitory effect,
      suggesting that this compound was not a mechanism-based inactivator of CYP3A4 or
      CYP3A5 when BFC was used as the substrate. Overall, our study provides the first
      demonstration that trans-resveratrol inhibits, in vitro, a substrate oxidation
      reaction catalyzed by human recombinant CYP3A4 and CYP3A5.

PMID- 11294599
TI  - Comparison of pulmonary vascular function and structure in early and established
      hypoxic pulmonary hypertension in rats.
AB  - In pulmonary hypertension, changes in pulmonary vascular structure and function
      contribute to the elevation in pulmonary artery pressure. The time-courses for
      changes in function, unlike structure, are not well characterised. Medial
      hypertrophy and neomuscularisation and reactivity to vasoactive agents were
      examined in parallel in main and intralobar pulmonary arteries and salt-perfused
      lungs from rats exposed to hypoxia (10% O2) for 1 and 4 weeks (early and
      established pulmonary hypertension, respectively). After 1 week of hypoxia, in
      isolated main and intralobar arteries, contractions to 5-hydroxytryptamine and
      U46619 (thromboxane-mimetic) were increased whereas contractions to angiotensins
      I and II and relaxations to acetylcholine were reduced. These alterations varied
      quantitatively between main and intralobar arteries and, in many instances,
      regressed between 1 and 4 weeks. The alterations in reactivity did not
      necessarily link chronologically with alterations in structure. In perfused
      lungs, constrictor responses to acute alveolar hypoxia were unchanged after 1
      week but were increased after 4 weeks, in conjunction with the neomuscularisation
      of distal alveolar arteries. The data suggest that in hypoxic pulmonary
      hypertension, the contribution of altered pulmonary vascular reactivity to the
      increase in pulmonary artery pressure may be particularly important in the early
      stages of the disease.

PMID- 11294600
TI  - Interaction between nitric oxide and renal myogenic autoregulation in
      normotensive and hypertensive rats.
AB  - Blood pressure fluctuates continuously throughout life and autoregulation is the
      primary mechanism that isolates the kidney from this fluctuation. Compared with
      Wistar rats, Brown Norway (B-N) rats display impaired renal myogenic
      autoregulation when blood pressure fluctuation is increased. They also are very
      susceptible to hypertension-induced renal injury. Because blockade of nitric
      oxide augments myogenic autoregulation in Wistar rats, we compared the response
      of the myogenic system in B-N rats to nitric oxide blockade with that of other
      strains [Wistar, Sprague-Dawley, Long-Evans, spontaneously hypertensive (SHR)].
      Renal blood flow dynamics were assessed in isoflurane anesthetized rats before
      and after inhibition of nitric oxide synthase by Lomega-nitro-arginine methyl
      ester (L-NAME, 10 mg/kg, iv). Under control conditions, myogenic autoregulation
      in the B-N rats was weaker than in the other strains. Myogenic autoregulation was
      not augmented after L-NAME administration in the SHR, but was augmented in all
      the normotensive rats. The enhancement was significantly greater in B-N rats so
      that after L-NAME the efficiency of autoregulation did not differ among the
      strains. The data suggest that nitric oxide is involved in the impaired myogenic
      autoregulation seen in B-N rats. Furthermore, the similarity of response in
      Wistar, Long-Evans, and Sprague-Dawley rats suggests that modulation by nitric
      oxide is a fundamental property of renal myogenic autoregulation.

PMID- 11294601
TI  - Epinephrine causes a reduction in lymph node cell output in sheep.
AB  - The lymphatic system has a critical role in the return of fluids, proteins, and
      cells to the circulatory system. However, the effects of stress, including
      exercise, on this system have not been adequately studied. We investigated the
      effect of a physiological dose (1 mg) of epinephrine (Epi) on lymph flow, cell
      concentration, and lymphocyte subsets in efferent subcutaneous lymph in sheep.
      Blood leukocyte numbers, differential, lymphocyte subsets, and blood and lymph
      pools of lymphocytes were determined simultaneously. A significant acute increase
      in lymph flow was followed by a post-injection decrease in flow and cellular
      output. No changes in lymphocyte subsets or pools of lymphocytes were seen in
      either blood or lymph. The timing of elevated plasma and lymph concentrations of
      Epi and norepinephrine (NE) corresponded with the increased lymph flow. In
      conclusion, Epi injection caused no change in lymphocyte subset distribution,
      leukocyte concentration, or pools of lymphocytes. A decrease in lymph flow and
      cellularity was documented post-injection, indicating that lymphatic tissue has
      no role in the leukocytosis seen after Epi injection. Lymphocyte retention by
      lymph nodes, however, may contribute to post-injection lymphopenia.

PMID- 11294602
TI  - Therapeutic implications of hypothermic and hyperthermic temperature conditions
      in stroke patients.
AB  - Brain temperature is an important variable in determining the outcome of cerebral
      ischemia; increases in core temperature escalate neural damage whereas decreases
      in core temperature reduce damage. Fever induction often occurs in patients prior
      to or as a direct or indirect result of the ischemic insult, with a worsened
      stroke outcome, compared with non-febrile ischemic patients. Most importantly,
      post-ischemic hypothermia reduces long term neural damage and associated
      behavioral deficits in animals studied for up to a year after the ischemic
      insult. This review discusses the importance of monitoring the brain temperature
      of stroke patients and implemention of therapeutic thermoregulatory strategies to
      reduce the temperature of ischemic patients.

PMID- 11294603
TI  - Protective and regenerative response endogenously induced in the ischemic brain.
AB  - Neuronal cells are highly vulnerable to ischemic insult. Because adult neurons
      are highly differentiated and cannot self-propagate, loss of neurons often
      results in functional deficits in mammalian brains. However, it has recently been
      shown that neurons and neuronal circuits exhibit protective and regenerative
      responses in a rodent model of experimental ischemia. At first, neurons respond
      by producing several protective proteins such as heat shock proteins (HSPs) after
      sublethal ischemia and then acquire tolerance against a subsequent ischemic
      insult (ischemic tolerance). Once neurons suffer irreversible injury, two repair
      processes, neurogenesis and synaptogenesis, are endogenously induced. Neuronal
      stem and (or) progenitor cells can proliferate in two brain areas in adult
      animals: the subventricular zone and the subgranular zone in the dentate gyrus.
      After ischemic insult, these stem (progenitor) cells proliferate and
      differentiate into neurons in the dentate gyrus of the hippocampus. Reactive
      synaptogenesis has been also observed in the injured brain following a period of
      long-term infarction, but it is unclear if it can compensate for disconnected
      circuits. Understanding the molecular mechanism underlying these protective and
      regenerative responses will be important in developing a new strategy for aimed
      at the augmentation of resistance against ischemic insult and the replacement of
      injured neurons and neuronal circuits.

PMID- 11294604
TI  - Therapeutic potential of dietary phase 2 enzyme inducers in ameliorating diseases
      that have an underlying inflammatory component.
AB  - Many diseases associated with ageing have an underlying oxidative stress and
      accompanying inflammatory component, for example, Alzheimer's disease or
      atherosclerosis. Reviewed in this manuscript are: the role of oxidative stress in
      activating the transcription factor nuclear factor kappa B (NFkappaB), the role
      of NFkappaB in activating proinflammatory gene transcription, strong oxidants
      produced by cells, anti-oxidant defense systems, the central role of phase 2
      enzymes in the anti-oxidant defense, dietary phase 2 enzyme inducers and evidence
      that dietary phase 2 enzymes decrease oxidative stress. It is likely that a diet
      containing phase 2 enzyme inducers may ameliorate or even prevent diseases that
      have a prominent inflammatory component to them. Research should be directed into
      the potential therapeutic effects of dietary phase 2 enzyme inducers in
      ameliorating diseases with an underlying oxidative stress and inflammatory
      component to them.

PMID- 11294605
TI  - Understanding and managing ischemic stroke.
AB  - Transient or permanent focal brain injury following acute thromboembolic
      occlusion develops from a complex cascade of pathophysiological events. The
      processes of excitotoxicity, peri-infarct depolarisation, inflammation, and
      apoptosis within the ischemic penumbra are proposed. While the translation of
      therapeutic agents from the animal models to human clinical trials have been
      disappointing, there remains an atmosphere of optimism as a result of the
      development of new diagnostic and therapeutic approaches, which include
      physiological, as opposed to pharmacological, intervention. This article provides
      an insight into the understanding of cerebral ischemia, together with current and
      future treatment strategies.

PMID- 11294606
TI  - (T2AG3)n telomeric sequence hybridization suggestive of centric fusion in
      karyotype marsupials evolution.
AB  - It has been suggested that the karyotype of the marsupials derived from a low
      diploid number (2n = 14) which originated, through fissions of biarmed
      chromosomes, the karyotypes with a higher 2n. The telomeric sequence (T2AG3)n was
      in situ hybridized to the chromosomes of Gracilinanus microtarsus and G. emiliae,
      Micoureus demerarae and Marmosa murina, species with 2n = 14, in Monodelphis sp.,
      M. domestica, M. kunsi and M. brevicaudata with 2n = 18, and in Lutreolina
      crassicaudata, Didelphis albiventris, Chironectes minimus, Philander opossum and
      P. frenata, all of them with 2n = 22. The probe hybridization occurred in the
      telomeric regions of both arms, short and long, of all chromosomes of the
      complement of all individuals of all species analysed. However, in some pairs of
      the karyotypes of Gracilinanus microtarsus and Micoureus demerarae (with 2n =
      14), and in Monodelphis sp., M. domestica, M. kunsi and M. brevicaudata (2n = 18)
      ectopic signs of hybridization were detected proximal to the centromeres,
      suggesting the retention of this telomeric sequence in the centromeric regions of
      some chromosomes of these species. Based on these results, it is proposed that
      the karyotype of marsupials evolved from a 2n = 22 to a 2n = 14, by means of
      chromosomal fusions.

PMID- 11294607
TI  - Morphological differentiation and possible origin of B chromosomes in natural
      Brazilian population of Astyanax scabripinnis (Pisces, Characidae).
AB  - Specimens of Astyanax scabripinnis from three different altitudes (1920, 1800 and
      700 m) along the Ribeirao Grande stream in the Campos do Jordao region (Sao Paulo
      State, Brazil) were investigated. The same diploid number, 2n = 50, was detected
      in the three populations, with the following karyotypic constitution: 6M, 22SM,
      10ST and 12A. The populations located at 1920 and 1800 m altitude presented a
      high incidence of B chromosomes varying in number (0-2), shape (meta- and
      submetacentrics), size (large and small) and sex-related frequency (they were
      more frequent among females). The two morphologically variant B chromosomes
      probably evolved from a metacentric macrochromosome, which is the most commonly
      observed B chromosome in several A. scabripinnis populations.

PMID- 11294608
TI  - The Drosophila serido speciation puzzle: putting new pieces together.
AB  - The D. serido superspecies is a complex mosaic of populations distributed over a
      vast part of South America and showing various degrees of genetical divergence.
      We have analyzed its chromosomal constitution in 16 new localities of
      southeastern and southern Brazil. Both the metaphase and salivary gland
      chromosomes show a sharp split of these populations in two groups. Four
      populations, fixed for inversion 2e8 and showing the type I karyotype, represent
      the southwestern limit of D. serido type B, which inhabits the Cerrado in central
      western Brazil. The remaining populations are homozygous for 2x7, an inversion
      also fixed in the Caatinga populations of northeastern Brazil. However, their
      karyotype, in those populations analyzed, belong to a different type (V) from
      that of the Caatinga populations. Populations in this second group are
      polymorphic for five inversions on chromosome 2 plus another on chromosome 5 and
      show considerable interpopulation differentiation. The breakpoints of chromosome
      2 inversions are described and the inversion loops of several heterokaryotypes
      are presented. Biogeographical information suggests that there are clear
      ecological differences between the two groups of populations as well as among the
      populations within the second group. Thepossible role of host plants in promoting
      the genetic divergence among the D. serido populations is discussed.

PMID- 11294609
TI  - The kinetics of transposable element autoregulation.
AB  - Kinetic modeling of the self-regulatory mechanisms of transposable elements (TEs)
      involving interactions of one or a few gene products makes predictions that are
      often at odds with observed results. In particular, explanations of TE
      autorepression at high copy number that invoke a decrease in number of active
      monomers through dimerization, amyloidization, and protein-mRNA binding to create
      an inactive state are not supported by analysis of the corresponding kinetic
      models. This is also true for similar mRNA-mRNA binding models. Self-repression
      in mariner as well as other TEs can, however, be explained by a host-independent
      model in which inactive dimers compete with monomers for TE binding sites at the
      ends of the element. This model would also allow heterodimer poisoning to down
      regulate transposition in the presence of divergent nonautonomous elements, since
      nondivergent monomers would be required at both TE ends for transposition.

PMID- 11294610
TI  - Sub-cellular localisation of the white/scarlet ABC transporter to pigment granule
      membranes within the compound eye of Drosophila melanogaster.
AB  - The white, scarlet, and brown genes of Drosophila melanogaster encode ABC
      transporters involved with the uptake and storage of metabolic precursors to the
      red and brown eye colour pigments. It has generally been assumed that these
      proteins are localised in the plasma membrane and transport precursor molecules
      from the heamolymph into the eye pigment cells. However, the immuno-electron
      microscopy experiments in this study reveal that the White and Scarlet proteins
      are located in the membranes of pigment granules within pigment cells and
      retinula cells of the compound eye. No evidence of their presence in the plasma
      membrane was observed. This result suggests that, rather than tranporting
      tryptophan into the cell across the plasma membrane, the White/Scarlet complex
      transports a metabolic intermediate (such as 3-hydroxy kynurenine) from the
      cytoplasm into the pigment granules. Other functional implications of this new
      finding are discussed.

PMID- 11294611
TI  - Chromosomal location of ribosomal DNA (rDNA), (GATA)n and (TTAGGG)n telomeric
      repeats in the neogastropod Fasciolaria lignaria (Mollusca: Prosobranchia).
AB  - This paper reports on a successful application of fluorescent in situ
      hybridization (FISH) with three repetitive DNA probes (ribosomal DNA (rDNA),
      (GATA)n and (TTAGGG)n) in the chromosomes of Fasciolaria lignaria (Mollusca:
      Prosobranchia: Neogastropoda). rDNA FISH consistently identified four chromosome
      pairs per spread in the three examined specimens. The telomeric sequence
      (TTAGGG)n hybridized with termini of all chromosomes. GATA FISH revealed
      abundant, dispersed minisatellite regions which were not associated to the XY sex
      determining mechanism as indicated by the absence of a Y specific pattern of
      labelling.

PMID- 11294612
TI  - Molecular cloning and chromosomal localization of human salt-tolerant protein.
AB  - We have isolated a novel human cDNA coding for human salt-tolerant protein
      (HSTP), that is a homologue of the rat salt-tolerant protein (STP) and may
      contribute to salt-induced hypertension by modulating renal cation transport. The
      nucleotide sequence (1988bp) of the HSTP cDNA contains an open reading frame
      encoding a polypeptide comprising 545 amino acids, two residues fewer than the
      rat STP cDNA. The predicted amino acid sequence exhibits 92% identity to that of
      the rat protein. HSTP contains predicted coiled-coil domains and Src Homology 3
      domain, and shows a high degree of identity to CIP4 (Cdc42 target protein) and
      human Trip 10 (thyroid-hormone receptor interacting protein). We have mapped the
      HSTP gene to human chromosome 19 by fluorescence in situ hybridization.

PMID- 11294613
TI  - Distribution of the transposable element Minos in the genus Drosophila.
AB  - We analyzed 28 species of the genus Drosophila for the presence of the Tc1-like
      transposable element Minos using Southern blot hybridization under high
      stringency conditions. The Minos transposon was found in members of both the
      Drosophila and the Sophophora subgenus showing a distribution that is wider if
      compared to other well-studied Drosophila transposons such as the P element, hobo
      and mariner. The presence of Minos-hybridizing sequences was discontinuous in the
      Sophophora subgenus, especially in the melanogaster species group. Using the
      Polymerase Chain Reaction we amplified a portion corresponding to the putative
      Minos transposase from different Drosophila species. Cloning and sequence
      analysis of randomly selected Minos copies from D. mojavensisis, D. saltans and
      D. willistoni supports the idea that event(s) of horizontal transfer may have
      contributed to the spreading of this transposon in the Drosophila genus.

PMID- 11294614
TI  - Use of three different marker systems to estimate genetic diversity of Indian
      elite rice varieties.
AB  - Genetic diversity among 42 Indian elite rice varieties, which is important for
      selection of parents for conventional breeding and hybrid program, was evaluated
      using three different types of DNA markers and parentage analysis. Random
      amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR) and
      sequence tagged microsatellite site (STMS) markers resulted in mean
      heterozygosity values of 0.429, 0.675 and 0.882 over all loci, respectively, and
      marker index values of 2.21, 4.05 and 5.49, respectively. The three molecular
      marker systems together provide wider genome coverage and, therefore, would be a
      better indicator of the genetic relationships among the 42 elite rice cultivars
      than those revealed using individual molecular markers. A total of 153 bands
      (91%) were polymorphic out of 168 bands amplified, considering all the markers
      together. The average genetic similarity coefficient across all the 861 cultivar
      pairs was 0.70 while the average coefficient of parentage was 0.10. Cluster
      analysis revealed that there was a very poor correlation (correlation coefficient
      <0.1) between dendrograms generated using coefficients of parentage and molecular
      marker generated genetic similarities, which can be attributed to selection
      pressure, genetic drift, sampling of loci and unknown relationships among
      supposedly unrelated ancestors.

PMID- 11294615
TI  - An assessment of the phylogenetic relationship among sugarcane and related taxa
      based on the nucleotide sequence of 5S rRNA intergenic spacers.
AB  - 5S rRNA intergenic spacers were amplified from two elite sugarcane (Saccharum
      hybrids) cultivars and their related taxa by polymerase chain reaction (PCR) with
      5S rDNA consensus primers. Resulting PCR products were uniform in length from
      each accession but exhibited some degree of length variation among the sugarcane
      accessions and related taxa. These PCR products did not always cross hybridize in
      Southern blot hybridization experiments. These PCR products were cloned into a
      commercial plasmid vector PCR 2.1 and sequenced. Direct sequencing of cloned PCR
      products revealed spacer length of 231-237 bp for S. officinarum, 233-237 for
      sugarcane cultivars, 228-238 bp for S. spontaneum, 239-252 bp for S. giganteum,
      385-410 bp for Erianthus spp., 226-230 bp for Miscanthus sinensis Zebra, 206-207
      bp for M. sinensis IMP 3057, 207-209 bp for Sorghum bicolor, and 247-249 bp for
      Zea mays. Nucleotide sequence polymorphism were found at both the segment and
      single nucleotide level. A consensus sequence for each taxon was obtained by
      Align X. Multiple sequences were aligned and phylogenetic trees constructed using
      Align X. CLUSTAL and DNAMAN programs. In general, accessions of the following
      taxa tended to group together to form distinct clusters: S. giganteum, Erianthus
      spp., M. sinensis, S. bicolor, and Z. mays. However, the two S. officinarum
      clones and two sugarcane cultivars did not form distinct clusters but
      interrelated within the S. spontaneum cluster. The disclosure of these 5S rRNA
      intergenic spacer sequences will facilitate marker-assisted breeding in
      sugarcane.

PMID- 11294617
TI  - Patient communication in hormone therapy.
AB  - Common regimens of HRT therapy are reviewed, including common routes of hormone
      administration. Inconsistent patterns of HRT use are discussed, including the
      reasons women most often give for discontinuing hormone therapies. Specific
      issues related to misperceptions and fears regarding HRT are clarified, and
      specific, focused patient education formats are discussed to address women's
      common concerns about HRT. Obstacles to HRT use are elucidated, with suggestions
      for clinicians about how to communicate more effectively with women: clinicians
      must focus on emotional and physical aspects of HRT choices and tailor therapies
      to the individual patient. Discussing frankly the very serious concerns of women
      regarding the association between lobular breast cancer and endometrial cancer is
      important; discussing and preparing women for possible side effects helps
      patients cope better if and when side effects occur. Finally, offering a wide
      variety of HRT therapies provides women with a broader choice if an initial
      regimen is unsuccessful.

PMID- 11294616
TI  - The relationship between the duration of menopause and lower urinary tract
      symptoms in women aged 40 to 59.
AB  - OBJECTIVE: To evaluate lower urinary tract symptoms in pre- and perimenopausal
      women. METHOD: Four hundred seventy-one women between 40 and 59 years of age with
      perimenopausal complaints attending our menopause clinic were evaluated for lower
      urinary tract symptoms by using the International Prostate Symptom Score
      questionnaire. The women were categorized by subgroups as being in premenopause,
      early menopause (1-<5 years' duration) and late menopause (> or = 5 years'
      duration), and by decade. Statistical evaluations were done by unpaired t test,
      one-way ANOVA, and simple and multiple regression analyses. RESULTS: The
      premenopausal women in their forties had more severe lower urinary tract symptoms
      when compared with early and late menopausal women. In comparisons the nocturia
      score tended to rise with age. CONCLUSION: Lower urinary tract symptoms appear to
      be affected by both age and the duration of menopause in women in their forties
      and fifties, and this observation might be taken into consideration while
      evaluating this age group for lower urinary tract symptoms.

PMID- 11294618
TI  - New aspects of injectable contraception.
AB  - Despite the availability of efficacious and safe contraceptive agents, not all
      women's contraceptive needs are being met. An injectable contraceptive method
      offers convenience and encourages compliance, both very important aspects for
      women seeking ideal contraception. Depot medroxyprogesterone acetate (DMPA) is a
      long-acting injectable, and is highly effective; one injection provides 3 months
      of contraception. Drawbacks of DMPA include irregular bleeding and a slow return
      to fertility. A new monthly injectable contraceptive agent is medroxyprogesterone
      acetate/estradiol cypionate suspension (Lunelle). It provides menstrual
      regulation and a rapid return to fertility. The estrogen ensures a withdrawal
      bleed monthly; however, women with contraindications to estrogen-containing
      contraception are not candidates for Lunelle.

PMID- 11294619
TI  - HRT dosing regimens: continuous versus cyclic-pros and cons.
AB  - The introduction of new products, lower dosages, and better continuous and cyclic
      regimens allows for individualized treatment aimed at minimizing risk and side
      effects, while maximizing confidence and compliance. Since the major side effect
      of HRT that discourages long-term use is vaginal bleeding, newer regimens are
      designed to minimize it. The lowest doses of estrogen currently approved by the
      FDA for prevention of osteoporosis include 0.3 mg esterified estrogens, 0.025
      microg transdermal estradiol patch, and 0.5 mg micronized estradiol. In most
      naturally menopausal women or those over 65 years of age, conjugated estrogen 0.3
      mg (with adequate calcium intake) is protective against bone loss and
      cardiovascular disease. These low doses are often used with cyclic progestins
      every 3 to 4 months. Advantages of cyclic therapy using low-dose estrogen include
      minimal progestin exposure, low rate of withdrawal bleeding, lowered side
      effects, and, often, higher comfort level. Cyclic estrogen regimens with higher
      doses have been in use longer, but they often necessitate more frequent progestin
      treatment and may result in cyclic bleeding or breast tenderness. While HDL- and
      LDL-cholesterol changes are greater and more beneficial during higher-dose oral
      cyclic therapy, the large increase in triglycerides is of concern. The most
      commonly used continuous combined regimens include conjugated estrogen plus daily
      progestin orally or the combination estradiol/norethindrone acetate transdermal
      patch. Continuous combined regimens are simple and easy-to-use, and are designed
      to minimize bleeding. Multiple studies suggest that the mechanism of benefit
      provided by estrogen goes beyond estrogen's favorable impact on lipoproteins,
      which is blunted by daily use of synthetic progestins.

PMID- 11294620
TI  - Determination of the disulfide structure of sillucin, a highly knotted, cysteine
      rich peptide, by cyanylation/cleavage mass mapping.
AB  - The disulfide structure of sillucin, a highly knotted, cysteine-rich,
      antimicrobial peptide, isolated from Rhizomucor pusillus, has been determined to
      be Cys2--Cys7, Cys12--Cys24, Cys13--Cys30, and Cys14--Cys21 by disulfide mass
      mapping based on partial reduction and CN-induced cleavage enabled by
      cyanylation. The denatured 30-residue peptide was subjected to partial reduction
      by tris(2-carboxyethyl)phosphine hydrochloride at pH 3 to produce a mixture of
      partially reduced sillucin species; the nascent sulfhydryl groups were
      immediately cyanylated by 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate.
      The cyanylated species, separated and collected during reversed phase high
      performance liquid chromatography, were treated with aqueous ammonia, which
      cleaved the peptide chain on the N-terminal side of cyanylated cysteine residues.
      The CN-induced cleavage mixture was analyzed by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry before and after complete reduction
      of residual disulfide bonds in partially reduced and cyanylated species to mass
      map the truncated peptides to the sequence. Because the masses of the CN-induced
      cleavage fragments of both singly and doubly reduced and cyanylated sillucin are
      related to the linkages of the disulfide bonds in the original molecule, the
      presence of certain truncated peptide(s) can be used to positively identify the
      linkage of a specific disulfide bond or exclude the presence of other possible
      linkages.

PMID- 11294621
TI  - Platelet-activating factor acetylhydrolases: broad substrate specificity and
      lipoprotein binding does not modulate the catalytic properties of the plasma
      enzyme.
AB  - Platelet-activating factor acetylhydrolases (PAF-AHs) are a group of enzymes that
      hydrolyze the sn-2 acetyl ester of PAF (phospholipase A(2) activity) but not
      phospholipids with two long fatty acyl groups. Our previous studies showed that
      membrane-bound human plasma PAF-AH (pPAF-AH) accesses its substrate only from the
      aqueous phase, which raises the possibility that this enzyme can hydrolyze a
      variety of lipid esters that are partially soluble in the aqueous phase. Here we
      show that pPAF-AH has broad substrate specificity in that it hydrolyzes short
      chain diacylglycerols, triacylglycerols, and acetylated alkanols, and displays
      phospholipase A(1) activity. On the basis of all of the substrate specificity
      results, it appears that the minimal structural requirement for a good pPAF-AH
      substrate is the portion of a glyceride derivative that includes an sn-2 ester
      and a reasonably hydrophobic chain in the position occupied by the sn-1 chain. In
      vivo, pPAF-AH is bound to high and low density lipoproteins, and we show that the
      apparent maximal velocity for this enzyme is not influenced by lipoprotein
      binding and that the enzyme hydrolyzes tributyroylglycerol as well as the
      recombinant pPAF-AH does. Broad substrate specificity is also observed for the
      structurally homologous PAF-AH which occurs intracellularly [PAF-AH(II)] as well
      as for the PAF-AH from the lower eukaryote Physarum polycephalum although pPAF-AH
      and PAF-AH(II) tolerate the removal of the sn-3 headgroup better than the PAF-AH
      from P. polycephalum does. In contrast, the intracellular PAF-AH found in
      mammalian brain [PAF-AH(Ib) alpha 1/alpha 1 and alpha 2/alpha 2 homodimers] is
      more selectively operative on compounds with a short acetyl chain although this
      enzyme also displays significant phospholipase A(1) activity.

PMID- 11294622
TI  - Regulation of type II phosphatidylinositol phosphate kinase by tyrosine
      phosphorylation in bovine rod outer segments.
AB  - Type II phosphatidylinositol phosphate kinase (PIPKII) is an enzyme responsible
      for the synthesis of phosphatidylinositol-4,5-bisphosphate (PI-4,5-P(2)) from
      phosphatidylinositol-5-phosphate (PI-5-P). In this study, we demonstrate the
      presence of PIPKII alpha in bovine photoreceptor rod outer segments (ROS) and the
      involvement of tyrosine phosphorylation in the regulation of its activity. PIPKII
      activity in bovine ROS was verified by the preferential conversion of synthetic
      dipalmitoyl PI-5-P to PI-4,5-P(2), lack of effect of phosphatidic acid,
      inhibition by heparin, immunoreaction with an anti-PIPKII alpha antibody on
      Western blots, and immunocytochemical localization in bovine and rat ROS by anti
      PIPKII alpha. Immunoprecipitates of bovine ROS with the anti-PIPKII alpha
      antibody possessed PIPK enzymatic activity and preferentially used PI-5-P as
      substrate for PI-4,5-P(2) biosynthesis. The activity of PIPKII was greatly
      increased under conditions favoring tyrosine phosphorylation in ROS, and PIPKII
      activity was immunoprecipitated with anti-phosphotyrosine (anti-PY) antibodies
      from tyrosine phosphorylated ROS. Preincubation of ROS with tyrosine kinase
      inhibitors almost abolished the kinase activity in the anti-PY
      immunoprecipitates. Immunoblot analysis showed that PIPKII alpha was present in
      anti-PY immunoprecipitates from phosphorylated ROS but not from nonphosphorylated
      controls. We conclude that PIPKII alpha is present in ROS and that its activity
      is regulated by tyrosine phosphorylation.

PMID- 11294623
TI  - ARF binds the C-terminal region of the Escherichia coli heat-labile toxin (LTA1)
      and competes for the binding of LTA2.
AB  - Cholera toxin (CT) and the heat-labile enterotoxin (LT) from Escherichia coli are
      highly related in terms of structure and biochemical activities and are the
      causative agents of cholera and traveler's diarrhea, respectively. The
      pathophysiological action of these toxins requires their activity as ADP
      ribosyltransferases, transferring the ADP-ribose moiety from NAD onto the
      stimulatory, regulatory component of adenylyl cyclase, Gs. This reaction is
      highly dependent on the protein cofactor, termed ADP-ribosylation factor (ARF),
      that is itself a 20 kDa regulatory GTPase. In this study, we define sites of
      interaction between LTA and human ARF3. The residues identified as important to
      ARF binding include several of those previously shown to bind to the A2 subunit
      of the toxin and those important to the organization of two flexible loops,
      previously implicated as regulators of substrate entry. A model for how ARF acts
      to enhance the catalytic activity is proposed. A critical portion of the overlap
      between ARF and LTA(2) in binding LTA(1) includes a short region of sequence
      homology between LTA(2) and the switch II region of ARF. LTA(2) also interacted
      with ARF effectors in two-hybrid assays, and thus, we discuss the possibility
      that the LTA(2) subunit may function in cells as a partial ARF mimetic to compete
      for the binding of ARF to LTA(1) or regulate aspects of the toxin's transport
      from the cell surface to the ER.

PMID- 11294624
TI  - An XAS investigation of product and inhibitor complexes of Ni-containing GlxI
      from Escherichia coli: mechanistic implications.
AB  - Escherichia coli glyoxalase I (GlxI) is a metalloisomerase that is maximally
      activated by Ni(2+), unlike other known GlxI enzymes which are active with
      Zn(2+). The metal is coordinated by two aqua ligands, two histidines (5 and 74),
      and two glutamates (56 and 122). The mechanism of E. coli Ni-GlxI was
      investigated by analyzing Ni K-edge X-ray absorption spectroscopic (XAS) data
      obtained from the enzyme and complexes formed with the product, S-D
      lactoylglutathione, and various inhibitors. The analysis of X-ray absorption near
      edge structure (XANES) was used to determine the coordination number and geometry
      of the Ni site in the various Ni-GlxI complexes. Metric details of the Ni site
      structure were obtained from the analysis of extended X-ray absorption fine
      structure (EXAFS). Interaction of S-D-lactoylglutathione (product) or
      octylglutathione with the enzyme did not change the structure of the Ni site.
      However, analysis of XAS data obtained from a complex formed with a peptide
      hydroxamate bound to Ni-GlxI is consistent with this inhibitor binding to the Ni
      center by displacement of both water molecules. XANES analysis of this complex is
      best fit with a five-coordinate metal and, given the fact that both histidine
      ligands are retained, suggests the loss of a glutamate ligand. The loss of a
      glutamate ligand would preserve the neutral charge on the Ni complex and is
      consistent with the lack of a significant shift in the Ni K-edge energy in this
      complex. These data are compared with data obtained from the E. coli Ni-GlxI
      selenomethionine-substituted enzyme. The replacement of three methionine residues
      in the native enzyme with selenomethionine does not affect the structure of the
      Ni site. However, addition of the peptide hydroxamate inhibitor leads to the
      formation of a complex whose structure as determined by XAS analysis is
      consistent with inhibitor binding via displacement of both water molecules but
      retention of both histidine and glutamate ligands. This leads to an anionic
      complex, which is consistent with an observed 1.7 eV decrease in the Ni K-edge
      energy. Plausible reaction mechanisms for Ni-GlxI are discussed in light of the
      structural information available.

PMID- 11294625
TI  - Binding of nucleotides to nucleoside diphosphate kinase: a calorimetric study.
AB  - The source of affinity for substrates of human nucleoside diphosphate (NDP)
      kinases is particularly important in that its knowledge could be used to design
      more effective antiviral nucleoside drugs (e.g., AZT). We carried out a
      microcalorimetric study of the binding of enzymes from two organisms to various
      nucleotides. Isothermal titration calorimetry has been used to characterize the
      binding in terms of Delta G degrees, Delta H degrees and Delta S degrees.
      Thermodynamic parameters of the interaction of ADP with the hexameric NDP kinase
      from Dictyostelium discoideum and with the tetrameric enzyme from Myxococcus
      xanthus, at 20 degrees C, were similar and, in both cases, binding was enthalpy
      driven. The interactions of ADP, 2'deoxyADP, GDP, and IDP with the eukaryotic
      enzyme differed in enthalpic and entropic terms, whereas the Delta G degrees
      values obtained were similar due to enthalpy--entropy compensation. The binding
      of the enzyme to nonphysiological nucleotides, such as AMP--PNP, 3'deoxyADP, and
      3'-deoxy-3'-amino-ADP, appears to differ in several respects. Crystallography of
      the protein bound to 3'-deoxy-3'-amino-ADP showed that the drug was in a
      distorted position, and was unable to interact correctly with active site side
      chains. The interaction of pyrimidine nucleoside diphosphates with the hexameric
      enzyme is characterized by a lower affinity than that with purine nucleotides.
      Titration showed the stoichiometry of the interaction to be abnormal, with 9--12
      binding sites/hexamer. The presence of supplementary binding sites might have
      physiological implications.

PMID- 11294626
TI  - An increase in side chain entropy facilitates effector binding: NMR
      characterization of the side chain methyl group dynamics in Cdc42Hs.
AB  - Cdc42Hs is a signal transduction protein that is involved in cytoskeletal growth
      and organization. We describe here the methyl side chain dynamics of three forms
      of (2)H,(13)C,(15)N-Cdc42Hs [GDP-bound (inactive), GMPPCP-bound (active), and
      GMPPCP/PBD46-bound (effector-bound)] from (13)C-(1)H NMR measurements of
      deuterium T(1) and T(1 rho) relaxation times. A wide variation in flexibility was
      observed throughout the protein, with methyl axis order parameters (S(2)(axis))
      ranging from 0.2 to 0.4 (highly disordered) in regions near the PBD46 binding
      site to 0.8--1.0 (highly ordered) in some helices. The side chain dynamics of the
      GDP and GMPPCP forms are similar, with methyl groups on the PBD46 binding surface
      experiencing significantly greater mobility (lower S(2)(axis)) than those not on
      the binding surface. Binding of PBD46 results in a significant increase in the
      disorder and a corresponding increase in entropy for the majority of methyl
      groups. Many of the methyl groups that experience an increase in mobility are
      found in residues that are not part of the PBD46 binding interface. This entropy
      gain represents a favorable contribution to the overall entropy of effector
      binding and partially offsets unfavorable entropy losses such as those that occur
      in the backbone.

PMID- 11294627
TI  - Solution structure of BSTI: a new trypsin inhibitor from skin secretions of
      Bombina bombina.
AB  - The three-dimensional solution structure of BSTI, a trypsin inhibitor from the
      European frog Bombina bombina, has been solved using (1)H NMR spectroscopy. The
      60 amino acid protein contains five disulfide bonds, which were unambiguously
      determined to be Cys (4--38), Cys (13--34), Cys (17--30), Cys (21--60), and Cys
      (40--54) by experimental restraints and subsequent structure calculations. The
      main elements of secondary structure are four beta-strands, arranged as two small
      antiparallel beta-sheets. The overall fold of BSTI is disk shaped and is
      characterized by the lack of a hydrophobic core. The presumed active site is
      located on a loop comprising residues 21--34, which is a relatively disordered
      region similar to that seen in many other protease inhibitors. However, the
      overall fold is different to other known protease inhibitors with the exception
      of a small family of inhibitors isolated from nematodes of the family Ascaris and
      recently also from the haemolymph of Apis mellifera. BSTI may thus be classified
      as a new member of this recently discovered family of protease inhibitors.

PMID- 11294628
TI  - Mechanism of reaction of acyl phosph(on)ates with the beta-lactamase of
      Enterobacter cloacae P99.
AB  - A series of acyl phosph(on)ates has been prepared to more closely examine the
      details of the interactions of this class of molecule with beta-lactamases. In
      general, they were found to react with the class C beta-lactamase of Enterobacter
      cloacae P99 in two ways, by acylation and by phosphylation. The acyl-enzymes
      generated by the former reaction were transiently stable with half-lives of
      between 3 and 45 s, of comparable lifetime therefore to those generated by the
      inhibitory beta-lactams cefotaxime, cefuroxime, and cefoxitin. On the other hand,
      phosphylation led to a completely inactive enzyme. In general, the second-order
      rate constants for acylation (k(cat)/K(m)) were larger than for phosphylation
      (k(i)). As expected on chemical grounds, phosphylation was found to be relatively
      more effective for the phosphonates than the phosphates. The acyl phosphates were
      much more effective acylating agents however. The acylation reaction was found to
      be enhanced by hydrophobic substituents in both the acyl and leaving group
      moieties. Thus, the most reactive compound in this series was benzo[b]thiophene-2
      carbonyl 2'-naphthyl phosphate with a K(m) value of 0.15 microM and a k(cat) of
      0.2 s(-1); k(cat)/K(m) is therefore 1.3 x 10(6) s(-1) M(-1), making this compound
      the most specific acyclic acylation reagent for this beta-lactamase yet
      described. Significant substrate inhibition by this compound suggested that
      further binding regions may be available for exploitation in inhibitor design. A
      linear free energy analysis showed that the transition states for acylation of
      the beta-lactamase by aroyl phosphates are analogues of the corresponding aryl
      boronic acid adducts. Molecular modeling suggested that the aroyl phosphates
      react with the P99 beta-lactamase with the aroyl group in the side chain/acyl
      group site of normal substrates and the phosphate in the leaving group site. In
      this orientation, the phosphate leaving group interacts strongly with Lys 315.

PMID- 11294629
TI  - Removing a hydrogen bond in the dimer interface of Escherichia coli manganese
      superoxide dismutase alters structure and reactivity.
AB  - Among manganese superoxide dismutases, residues His30 and Tyr174 are highly
      conserved, forming part of the substrate access funnel in the active site. These
      two residues are structurally linked by a strong hydrogen bond between His30 NE2
      from one subunit and Tyr174 OH from the other subunit of the dimer, forming an
      important element that bridges the dimer interface. Mutation of either His30 or
      Tyr174 in Escherichia coli MnSOD reduces the superoxide dismutase activity to 30-
      40% of that of the wt enzyme, which is surprising, since Y174 is quite remote
      from the active site metal center. The 2.2 A resolution X-ray structure of H30A
      MnSOD shows that removing the Tyr174-->His30 hydrogen bond from the acceptor side
      results in a significant displacement of the main-chain segment containing the
      Y174 residue, with local rearrangement of the protein. The 1.35 A resolution
      structure of Y174F-MnSOD shows that disruption of the same hydrogen bond from the
      donor side has much greater consequences, with reorientation of F174 having a
      domino effect on the neighboring residues, resulting in a major rearrangement of
      the dimer interface and flipping of the His30 ring. Spectroscopic studies on
      H30A, H30N, and Y174F mutants show that (like the previously characterized Y34F
      mutant of E. coli MnSOD) all lack the high pH transition of the wt enzyme. This
      observation supports assignment of the pH sensitivity of MnSOD to coordination of
      hydroxide ion at high pH rather than to ionization of the phenolic group of Y34.
      Thus, mutations near the active site, as in the Y34F mutant, as well as at remote
      positions, as in Y174F, similarly affect the metal reactivity and alter the
      effective pK(a) for hydroxide ion binding. These results imply that hydrogen
      bonding of the H30 imidazole N--H group plays a key role in substrate binding and
      catalysis.

PMID- 11294630
TI  - Structures of Escherichia coli histidinol-phosphate aminotransferase and its
      complexes with histidinol-phosphate and N-(5'-phosphopyridoxyl)-L-glutamate:
      double substrate recognition of the enzyme.
AB  - Histidinol-phosphate aminotransferase (HspAT) is a key enzyme on the histidine
      biosynthetic pathway. HspAT catalyzes the transfer of the amino group of L
      histidinol phosphate (Hsp) to 2-oxoglutarate to form imidazole acetol phosphate
      (IAP) and glutamate. Thus, HspAT recognizes two kinds of substrates, Hsp and
      glutamate (double substrate recognition). The crystal structures of native HspAT
      and its complexes with Hsp and N-(5'-phosphopyridoxyl)-L-glutamate have been
      solved and refined to R-factors of 19.7, 19.1, and 17.8% at 2.0, 2.2, and 2.3 A
      resolution, respectively. The enzyme is a homodimer, and the polypeptide chain of
      the subunit is folded into one arm, one small domain, and one large domain.
      Aspartate aminotransferases (AspATs) from many species were classified into
      aminotransferase subgroups Ia and Ib. The primary sequence of HspAT is less than
      18% identical to those of Escherichia coli AspAT of subgroup Ia and Thermus
      thermophilus HB8 AspAT of subgroup Ib. The X-ray analysis of HspAT showed that
      the overall structure is significantly similar to that of AspAT of subgroup Ib
      rather than subgroup Ia, and the N-terminal region moves close to the active site
      like that of subgroup Ib AspAT upon binding of Hsp. The folding of the main-chain
      atoms in the active site is conserved between HspAT and the AspATs, and more than
      40% of the active-site residues is also conserved. The eHspAT recognizes both Hsp
      and glutamate by utilizing essentially the same active-site folding as that of
      AspAT, conserving the essential residues for transamination reaction, and
      replacing and relocating some of the active-site residues. The binding sites for
      the phosphate and the alpha-carboxylate groups of the substrates are roughly
      located at the same position and those for the imidazole and gamma-carboxylate
      groups at the different positions. The mechanism for the double substrate
      recognition observed in eHspAT is in contrast to that in aromatic amino acid
      aminotransferase, where the recognition site for the side chain of the acidic
      amino acid is formed at the same position as that for the side chain of aromatic
      amino acids by large-scale rearrangements of the hydrogen bond networks.

PMID- 11294631
TI  - Ligand binding sites in Escherichia coli inorganic pyrophosphatase: effects of
      active site mutations.
AB  - Type I soluble inorganic pyrophosphatases (PPases) are well characterized both
      structurally and mechanistically. Earlier we measured the effects of active site
      substitutions on pH--rate profiles for the type I PPases from both Escherichia
      coli (E-PPase) and Saccharomyces cerevisae (Y-PPase). Here we extend these
      studies by measuring the effects of such substitutions on the more discrete steps
      of ligand binding to E-PPase, including (a) Mg(2+) and Mn(2+) binding in the
      absence of added ligand; (b) Mg(2+) binding in the presence of either P(i) or
      hydroxymethylbisphosphonate (HMBP), a competitive inhibitor of E-PPase; and (c)
      P(i) binding in the presence of Mn(2+). The active site of a type I PPase has
      well-defined subsites for the binding of four divalent metal ions (M1--M4) and
      two phosphates (P1, P2). Our results, considered in light of pertinent results
      from crystallographic studies on both E-PPase and Y-PPase and parallel functional
      studies on Y-PPase, allow us to conclude the following: (a) residues E20, D65,
      D70, and K142 play key roles in the functional organization of the active site;
      (b) the major structural differences between the product and substrate complexes
      of E-PPase are concentrated in the lower half of the active site; (c) the M1
      subsite is functionally isolated from the rest of the active site; and (d) the M4
      subsite is an especially unconstrained part of the active site.

PMID- 11294632
TI  - Negatively calcium-modulated membrane guanylate cyclase signaling system in the
      rat olfactory bulb.
AB  - The mechanism by which the individual odor signals are translated into the
      perception of smell in the brain is unknown. The signal processing occurs in the
      olfactory system which has three major components: olfactory neuroepithelium,
      olfactory bulb, and olfactory cortex. The neuroepithelial layer is composed of
      ciliated sensory neurons interspersed among supportive cells. The sensory neurons
      are the sites of odor transduction, a process that converts the odor signal into
      an electrical signal. The electrical signal is subsequently received by the
      neurons of the olfactory bulb, which process the signal and then relay it to the
      olfactory cortex in the brain. Apart from information about certain biochemical
      steps of odor transduction, there is almost no knowledge about the means by which
      the olfactory bulb and cortical neurons process this information. Through
      biochemical, functional, and immunohistochemical approaches, this study shows the
      presence of a Ca(2+)-modulated membrane guanylate cyclase (mGC) transduction
      system in the bulb portion of the olfactory system. The mGC is ROS-GC1. This is
      coexpressed with its specific modulator, guanylate cyclase activating protein
      type 1 (GCAP1), in the mitral cells. Thus, a new facet of the Ca(2+)-modulated
      GCAP1--ROS-GC1 signaling system, which, until now, was believed to be unique to
      phototransduction, has been revealed. The findings suggest a novel role for this
      system in the polarization and depolarization phenomena of mitral cells and also
      contradict the existing belief that no mGC besides GC-D exists in the olfactory
      neurons.

PMID- 11294633
TI  - DNA interaction of the tyrosine protein kinase inhibitor PD153035 and its N
      methyl analogue.
AB  - The brominated anilinoquinazoline derivative PD153035 exhibits a very high
      affinity and selectivity for the epidermal growth factor receptor tyrosine kinase
      (EGF-R TK) and shows a remarkable cytotoxicity against several types of tumor
      cell lines. In contrast, its N-methyl derivative, designated EBE-A22, has no
      effect on EGF-R TK but maintains a high cytotoxic profile. The present study was
      performed to explore the possibility that PD153035 and its N-methyl analogue
      might interact with double-stranded DNA, which is a primary target for many
      conventional antitumor agents. We studied the strength and mode of binding to DNA
      of PD153035 and EBE-A22 by means of absorption, fluorescence, and circular and
      linear dichroism as well as by a relaxation assay using human DNA topoisomerases.
      The results of various optical and gel electrophoresis techniques converge to
      show that both drugs bind to DNA and behave as typical intercalating agents. In
      particular, EBE-A22 unwinds supercoiled plasmid, stabilizes duplex DNA against
      heat denaturation, and produces negative CD and ELD signals, as expected for an
      intercalating agent. Extensive DNase I footprinting experiments performed with a
      large range of DNA substrates show that EBE-A22, but not PD153035, interacts
      preferentially with GC-rich sequences and discriminates against homooligomeric
      runs of A and T which are often cut more readily by the enzyme in the presence of
      the drug compared to the control. Altogether, the results provide the first
      experimental evidence that DNA is a target of anilinoquinazoline derivatives and
      suggest that this N-methylated ring system is a valid candidate for the
      development of DNA-targeted cytotoxic compounds. The possible relevance of
      selective DNA binding to activity is considered. The unexpected GC-selective
      binding properties of EBE-A22 entreat further exploration into the use of N
      methylanilinoquinazoline derivatives as tools for designing sequence-specific DNA
      binding ligands.

PMID- 11294634
TI  - Differential roles of ionic, aliphatic, and aromatic residues in membrane-protein
      interactions: a surface plasmon resonance study on phospholipases A2.
AB  - The roles of cationic, aliphatic, and aromatic residues in the membrane
      association and dissociation of five phospholipases A(2) (PLA(2)), including Asp
      49 PLA(2) from the venom of Agkistrodon piscivorus piscivorus, acidic PLA(2) from
      the venom of Naja naja atra, human group IIa and V PLA(2)s, and the C2 domain of
      cytosolic PLA(2), were determined by surface plasmon resonance analysis. Cationic
      interfacial binding residues of A. p. piscivorus PLA(2) (Lys-10) and human group
      IIa PLA(2) (Arg-7, Lys-10, and Lys-16), which mediate electrostatic interactions
      with anionic membranes, primarily accelerate the membrane association. In
      contrast, an aliphatic side chain of the C2 domain of cytosolic PLA(2) (Val-97),
      which penetrates into the hydrophobic core of the membrane and forms hydrophobic
      interactions, mainly slows the dissociation of membrane-bound protein. Aromatic
      residues of human group V PLA(2) (Trp-31) and N. n. atra PLA(2) (Trp-61, Phe-64,
      and Tyr-110) contribute to both membrane association and dissociation steps, and
      the relative contribution to these processes depends on the chemical nature and
      the orientation of the side chains as well as their location on the interfacial
      binding surface. On the basis of these results, a general model is proposed for
      the interfacial binding of peripheral proteins, in which electrostatic
      interactions by ionic and aromatic residues initially bring the protein to the
      membrane surface and the subsequent membrane penetration and hydrophobic
      interactions by aliphatic and aromatic residues stabilize the membrane-protein
      complexes, thereby elongating the membrane residence time of protein.

PMID- 11294635
TI  - Roles of amino acid residues near the chromophore of photoactive yellow protein.
AB  - To investigate the roles of amino acid residues around the chromophore in
      photoactive yellow protein (PYP), new mutants, Y42A, E46A, and T50A were
      prepared. Their spectroscopic properties were compared with those of wild-type,
      Y42F, E46Q, T50V, R52Q, and E46Q/T50V, which were previously prepared and
      specified. The absorption maxima of Y42A, E46A, and T50A were observed at 438,
      469, and 454 nm, respectively. The results of pH titration for the chromophore
      demonstrated that the chromophore of PYP mutant, like the wild-type, was
      protonated and bleached under acidic conditions. The red-shifts of the absorption
      maxima in mutants tended toward a pK(a) increase. Mutation at Glu46 induced
      remarkable shifts in the absorption maxima and pK(a). The extinction coefficients
      were increased in proportion to the absorption maxima, whereas the oscillator
      strengths were constant. PYP mutants that conserved Tyr42 were in the pH
      dependent equilibrium between two states (yellow and colorless forms). However,
      Y42A and Y42F were in the pH-independent equilibrium between additional
      intermediate state(s) at around neutral pH, in which yellow form was dominant in
      Y42F whereas the other was dominant in Y42A. These findings suggest that Tyr42
      acts as the hinge of the protein, and the bulk as well as the hydroxyl group of
      Tyr42 controls the protein conformation. In all mutants, absorbance at 450 nm was
      decreased upon flash irradiation and afterwards recovered on a millisecond time
      scale. However, absorbance at 340--370 nm was increased vice versa, indicating
      that the long-lived near-UV intermediates are formed from mutants, as in the case
      of wild-type. The lifetime changes with mutation suggest the regulation of proton
      movement through a hydrogen-bonding network.

PMID- 11294636
TI  - Inhibition of inflammatory endothelial responses by a pathway involving caspase
      activation and p65 cleavage.
AB  - Suppression of NF kappa B activation has been involved in the elimination of
      survival programs during endothelial cell (EC) apoptosis. We used alpha
      tocopheryl succinate (alpha-TOS) to trigger apoptosome formation and the
      subsequent activation of executioner caspases. The level of bcl-2 was reduced by
      alpha-TOS, and its downregulation potentiated and its overexpression suppressed
      pro-apoptotic effects of alpha-TOS, indicating a mitochondrial role in alpha-TOS
      induced apoptosis in EC. alpha-TOS treatment was associated with induction of
      TUNEL-positive apoptosis in EC with a high but not with a low proliferation
      index. The use of the pan-caspase inhibitor z-VAD.fmk suggested the involvement
      of caspases in cleavage of p65, and in inhibition of nuclear translocation of p65
      and NF kappa B-dependent transactivation of a gene construct encoding the green
      fluorescence protein elicited by TNF alpha in contact-arrested EC. The
      suppression by alpha-TOS of inflammatory EC responses induced by TNF alpha such
      as VCAM-1 mRNA and surface protein expression and shear-resistant arrest of
      monocytic cells were also reversed by z-VAD.fmk. NF kappa B-dependent
      transactivation was preserved in alpha-TOS-treated EC stably transfected with a
      caspase-noncleavable p65 mutant but not with its truncated form, thus
      establishing a direct link between alpha-TOS-induced effects and p65 cleavage.
      Our data infer a pathway by which caspase activation in EC inhibits NF kappa B
      dependent inflammatory activation and monocyte recruitment, and provide evidence
      for a relationship between pro-apoptotic and anti-inflammatory pathways.

PMID- 11294637
TI  - A correlation between differential structural features and the degree of
      endopeptidase activity of type A botulinum neurotoxin in aqueous solution.
AB  - Botulinum neurotoxin type A is one of the most toxic substances known to man
      (LD(50) for mouse 0.1 ng/kg). It is also an effective therapeutic drug against
      involuntary muscle disorders and for pain management. BoNT/A is a Zn(2+)
      endopeptidase which selectively cleaves SNAP-25 (synaptosomal-associated protein
      of 25 kDa), a critical component of the exocytotic machinery. Based on nucleotide
      sequence, BoNT/A is a 145 kDa protein, which appears as a 145 kDa protein band on
      sodium dodecyl sulfate--polyacrylamide gel electrophoresis. We have examined the
      structure of BoNT/A in aqueous solution, and found the structure in aqueous
      solution differs dramatically from that resolved by X-ray crystallography, both
      at secondary and at quaternary levels. In terms of secondary structure, BoNT/A in
      aqueous solution has about 47% beta-sheet structure as revealed by infrared
      spectroscopy, while X-ray crystallography revealed only 17% beta-sheet structure.
      In terms of quaternary structure, the estimated molecular mass of the native
      BoNT/A in aqueous solution ranged between 230 and 314 kDa, based on results from
      different chemical and biophysical techniques (native gel electrophoresis,
      chemical cross-linking, size exclusion chromatography, and fluorescence
      anisotropy). These results indicate that BoNT/A exists as a dimer in aqueous
      solution, which contrasts with the reported monomeric structure of BoNT/A based
      on X-ray crystallography. The dimeric form of BoNT/A can self-dissociate into the
      monomeric form at a concentration lower than 50 nM. This concentration-dependent
      structural change has a significant impact on the endopeptidase activity of
      BoNT/A: the catalytic efficiency of the monomeric BoNT/A is about 4-fold higher
      than that of its dimeric form. This difference implies a sterically restricted
      catalytic site of BoNT/A in the dimeric form of BoNT/A.

PMID- 11294638
TI  - In vitro conversion of propionate to pyruvate by Salmonella enterica enzymes: 2
      methylcitrate dehydratase (PrpD) and aconitase Enzymes catalyze the conversion of
      2-methylcitrate to 2-methylisocitrate.
AB  - Salmonella enterica serovar Typhimurium LT2 catabolizes propionate through the 2
      methylcitric acid cycle, but the identity of the enzymes catalyzing the
      conversion of 2-methylcitrate into 2-methylisocitrate is unclear. This work shows
      that the prpD gene of the prpBCDE operon of this bacterium encodes a protein with
      2-methylcitrate dehydratase enzyme activity. Homogeneous PrpD enzyme did not
      contain an iron-sulfur center, displayed no requirements for metal cations or
      reducing agents for activity, and did not catalyze the hydration of 2-methyl-cis
      aconitate to 2-methylisocitrate. It was concluded that the gene encoding the 2
      methyl-cis-aconitate hydratase enzyme is encoded outside the prpBCDE operon.
      Computer analysis of bacterial genome databases identified the presence of
      orthologues of the acnA gene (encodes aconitase A) in a number of putative prp
      operons. Homogeneous AcnA protein of S. enterica had strong aconitase activity
      and catalyzed the hydration of the 2-methyl-cis-aconitate to yield 2
      methylisocitrate. The purification of this enzyme allows the complete
      reconstitution of the 2-methylcitric acid cycle in vitro using homogeneous
      preparations of the PrpE, PrpC, PrpD, AcnA, and PrpB enzymes. However,
      inactivation of the acnA gene did not block growth of S. enterica on propionate
      as carbon and energy source. The existence of a redundant aconitase activity
      (encoded by acnB) was postulated to be responsible for the lack of a phenotype in
      acnA mutant strains. Consistent with this hypothesis, homogeneous AcnB protein of
      S. enterica also had strong aconitase activity and catalyzed the conversion of 2
      methyl-cis-aconitate into 2-methylisocitrate. To address the involvement of AcnB
      in propionate catabolism, an acnA and acnB double mutant was constructed, and
      this mutant strain cannot grow on propionate even when supplemented with
      glutamate. The phenotype of this double mutant indicates that the aconitase
      enzymes are required for the 2-methylcitric acid cycle during propionate
      catabolism.

PMID- 11294639
TI  - Redox properties of the PutA protein from Escherichia coli and the influence of
      the flavin redox state on PutA-DNA interactions.
AB  - The PutA flavoprotein from Escherichia coli is both a transcriptional repressor
      and a membrane-associated proline dehydrogenase. PutA represses transcription of
      the putA and putP genes by binding to the control region DNA of the put regulon
      (put intergenic DNA). Previous work has shown that FAD has a role in regulating
      the transcriptional repressor and membrane binding functions of the PutA protein.
      To test the influence of the FAD redox state on PutA--DNA interactions, we
      characterized the redox properties of the PutA flavoprotein from E. coli. At pH
      7.5, an E(m)(E--FAD/E--FADH(2)) of --0.076 V for the two-electron reduction of
      PutA-bound FAD was determined by potentiometric titrations. Stabilization of
      semiquinone species was not observed during potentiometric measurements.
      Dithionite reduction of PutA, however, caused formation of red anionic
      semiquinone. The E(m) value for the proline/Delta(1)-pyrroline-5-carboxylate
      couple was determined to be --0.123 V, demonstrating the reduction of PutA by
      proline is favored by a potential difference (Delta E degrees ') of more than
      0.045 V. Characterization of the PutA redox properties in the presence of put
      intergenic DNA revealed an E(m)(E(DNA)--FAD/E(DNA)--FADH(2)) of --0.086 V. The 10
      mV negative shift in E(m) corresponds to just a 2.3-fold increase in the
      dissociation constant of PutA with the DNA upon reduction of FAD. Thus, it
      appears the FAD redox state has little influence on the overall PutA--DNA
      interactions.

PMID- 11294640
TI  - Reaction of neuronal nitric-oxide synthase with 2,6-dichloroindolphenol and
      cytochrome c3+: influence of the electron acceptor and binding of Ca2+-activated
      calmodulin on the kinetic mechanism.
AB  - Binding of Ca(2+)-activated calmodulin (Ca(2+)-CaM) to neuronal nitric-oxide
      synthase (nNOS) increases the rate of 2,6-dichloroindolphenol (DCIP) reduction 2
      3-fold and that of cytochrome c(3+) 10-20-fold. Parallel initial velocity
      patterns indicated that both substrates were reduced via two-half reactions in a
      ping-pong mechanism. Product and dead-end inhibition data with DCIP were
      consistent with an iso ping-pong bi-bi mechanism; however, product and dead-end
      inhibition studies with cytochrome c(3+) were consistent with the (two-site) ping
      pong mechanism previously described for the NADPH-cytochrome P450 reductase
      catalyzed reduction of cytochrome c(3+) [Sem, D., and Kasper, C. (1994)
      Biochemistry 33, 12012--12021]. Dead-end inhibition by 2'-adenosine monophosphate
      (2'AMP) was competitive versus NADPH for both electron acceptors, although the
      value of the slope inhibition constant, K(is), was 25-30-fold greater with DCIP
      as the substrate than with cytochrome c(3+). The difference in the apparent
      affinity of 2'AMP is proposed to result from a rapidly equilibrating
      isomerization step that occurs in both mechanisms prior to the binding of NADPH.
      Thus, initial velocity, product, and dead-end inhibition data were consistent
      with a di-iso ping-pong bi-bi and an iso (two-site) ping-pong mechanism for the
      reduction of DCIP and cytochrome c(3+), respectively. The presence Ca(2+)-CaM did
      not alter the proposed kinetic mechanisms. The activated cofactor had a
      negligible effect on (k(cat)/K(m))(NADPH), while it increased (k(cat)/K(m))(DCIP)
      and (k(cat)/K(m))(cytc) 4.5- and 23-fold, respectively.

PMID- 11294641
TI  - Probing the active site of L-aspartate oxidase by site-directed mutagenesis: role
      of basic residues in fumarate reduction.
AB  - L-Aspartate oxidase is a very particular oxidase which behaves as a fumarate
      reductase in anaerobic conditions. Its primary and tertiary structures present
      remarkable similarity with the soluble fumarate reductase (FRD) from Shewanella
      frigidimarina and the flavin subunit of the membrane-bound fumarate reductase
      from Escherichia coli and Wolinella succinogenes. This and other extensive
      similarities are consistent with the idea that a common catalytic mechanism for
      the reduction of fumarate operates for all members of this enzyme group and that
      the key residues involved in the substrate binding and catalysis are conserved.
      This manuscript reports information about the role of these basic residues in L
      aspartate oxidase: R290, R386, H244, and H351. By means of site-directed
      mutagenesis, R290 and R386 are mutated to Leu and H351 and H244 are mutated both
      to Ala and Ser. H351, H244, and R386 mutants bind substrate analogues with higher
      dissociation constants and present lower k(cat)/K(m) values in the reduction of
      fumarate. Therefore, the results indicate that R386, H244, and H351 are important
      for the binding of the substrate fumarate and may play an important but not
      essential role in catalysis. R290, on the contrary, is mainly involved in
      catalysis and not in substrate binding since its mutation abolishes the catalytic
      activity without lowering the affinity of the enzyme for the substrate. The redox
      properties of all the mutants are identical to the wild-type. The findings are
      consistent with a model of L-aspartate oxidase active site based on the
      hypothesis proposed for the soluble FRD from S. fridimarina.

PMID- 11294642
TI  - Tandem action of glycosyltransferases in the maturation of vancomycin and
      teicoplanin aglycones: novel glycopeptides.
AB  - The glycopeptides vancomycin and teicoplanin are clinically important
      antibiotics. The carbohydrate portions of these molecules affect biological
      activity, and there is great interest in developing efficient strategies to make
      carbohydrate derivatives. To this end, genes encoding four glycosyltransferases,
      GtfB, C, D, E, were subcloned from Amycolatopsis orientalis strains that produce
      chloroeremomycin (GtfB, C) or vancomycin (GtfD, E) into Escherichia coli. After
      expression and purification, each glycosyltransferase (Gtf) was characterized for
      activity either with the aglycones (GtfB, E) or the glucosylated derivatives
      (GtfC, D) of vancomycin and teicoplanin. GtfB efficiently glucosylates vancomycin
      aglycone using UDP-glucose as the glycosyl donor to form desvancosaminyl
      vancomycin (vancomycin pseudoaglycone), with k(cat) of 17 min(-1), but has very
      low glucosylation activity, < or = 0.3 min(-1), for an alternate substrate,
      teicoplanin aglycone. In contrast, GtfE is much more efficient at glucosylating
      both its natural substrate, vancomycin aglycone (k(cat) = 60 min(-1)), and an
      unnatural substrate, teicoplanin aglycone (k(cat) = 20 min(-1)). To test the
      addition of the 4-epi-vancosamine moiety by GtfC and GtfD, synthesis of UDP-beta
      L-4-epi-vancosamine was undertaken. This NDP-sugar served as a substrate for both
      GtfC and GtfD in the presence of vancomycin pseudoaglycone (GtfC and GtfD) or the
      glucosylated teicoplanin scaffold, 7 (GtfD). The GtfC product was the 4-epi
      vancosaminyl form of vancomycin. Remarkably, GtfD was able to utilize both an
      unnatural acceptor, 7, and an unnatural nucleotide sugar donor, UDP-4-epi
      vancosamine, to synthesize a novel hybrid teicoplanin/vancomycin glycopeptide.
      These results establish the enzymatic activity of these four Gtfs, begin to probe
      substrate specificity, and illustrate how they can be utilized to make variant
      sugar forms of both the vancomycin and the teicoplanin class of glycopeptide
      antibiotics.

PMID- 11294643
TI  - Differential modulation of ACAT1 and ACAT2 transcription and activity by long
      chain free fatty acids in cultured cells.
AB  - Fatty acyl CoA and cholesterol are the substrates for cholesteryl ester synthesis
      by acyl coenzyme A:cholesterol acyltransferase (ACAT). Two ACAT genes have been
      identified; ACAT1 is expressed ubiquitously while ACAT2 is primarily expressed in
      intestine and liver. We tested effects of different free fatty acids (FFAs) on
      ACAT1 and ACAT2 expression and activity in HepG2 human hepatocytes and THP1 human
      macrophages. Incubation of oleic acid, arachidonic acid, or eicosapentaenoic
      acid, but not 25-hydroxycholesterol, induced ACAT1 mRNA levels 1.5--2-fold in
      HepG2, with no affect on ACAT2 mRNA. FFA had no affect on ACAT1 mRNA in THP1
      cells. To determine if FFAs affect ACAT1 or ACAT2 posttranscriptionally, cells
      were labeled with [(3)H]cholesterol in the presence of the different FFAs for 1-
      5 h. Both HepG2 and THP1 cells showed the greatest cholesteryl ester production
      with oleic acid. This was also confirmed by the observation that more [(3)H]oleic
      acid incorporated into CE compared to [(3)H]eicosapentaenoic acid, even though
      there was no difference in the total uptake of these FFAs. In ACAT-deficient
      SRD4, CHO cells stably transfected with human ACAT1 or ACAT2, ACAT1 expressing
      cells showed a strong preference for oleic acid while ACAT2 expressing cells
      utilized unsaturated FFAs. Acyl CoA substrate specificity was further tested in
      microsomes isolated from these cells as well as HepG2 and THP1. THP1 and ACAT1
      cells utilized oleoyl CoA preferentially. In contrast, HepG2 and ACAT2 microsomes
      utilized linolenoyl CoA as well. We conclude that FFAs increase ACAT1 mRNA levels
      in a cell specific manner, and furthermore that the ACAT reactions exhibit
      differential FFA utilization.

PMID- 11294644
TI  - Site-specific DNA damage at the GGG sequence by UVA involves acceleration of
      telomere shortening.
AB  - Telomere shortening is associated with cellular senescence. We investigated
      whether UVA, which contributes to photoaging, accelerates telomere shortening in
      human cultured cells. The terminal restriction fragment (TRF) from WI-38
      fibroblasts irradiated with UVA (365-nm light) decreased with increasing
      irradiation dose. Furthermore, UVA irradiation dose-dependently increased the
      formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in both WI-38
      fibroblasts and HL-60 cells. To clarify the mechanism of the acceleration of
      telomere shortening, we investigated site-specific DNA damage induced by UVA
      irradiation in the presence of endogenous photosensitizers using (32)P 5'-end
      labeled DNA fragments containing the telomeric oligonucleotide (TTAGGG)(4). UVA
      irradiation with riboflavin induced 8-oxodG formation in the DNA fragments
      containing telomeric sequence, and Fpg protein treatment led to chain cleavages
      at the central guanine of 5'-GGG-3' in telomere sequence. The amount of 8-oxodG
      formation in DNA fragment containing telomere sequence [5'-CGC(TTAGGG)(7)CGC-3']
      was approximately 5 times more than that in DNA fragment containing nontelomere
      sequence [5'-CGC(TGTGAG)(7)CGC-3']. Catalase did not inhibit this oxidative DNA
      damage, indicating no or little participation of H(2)O(2) in DNA damage. These
      results indicate that the photoexcited endogenous photosensitizer specifically
      oxidizes the central guanine of 5'-GGG-3' in telomere sequence to produce 8-oxodG
      probably through an electron-transfer reaction. It is concluded that the site
      specific damage in telomere sequence induced by UVA irradiation may participate
      in the increase of telomere shortening rate.

PMID- 11294645
TI  - Two mutations of basic residues within the N-terminus of HMG-1 B domain with
      different effects on DNA supercoiling and binding to bent DNA.
AB  - High mobility group (HMG) 1 protein and its two homologous DNA-binding domains, A
      and B ("HMG-boxes"), can bend and supercoil DNA in the presence of topoisomerase
      I, as well as recognize differently bent and distorted DNA structures, including
      four-way DNA junctions, supercoiled DNA and DNA modified with anticancer drug
      cisplatin. Here we show that the lysine-rich part of the linker region between A
      and B domains of HMG-1, the (85)TKKKFKD(91) sequence that is attached to the N
      terminus of the B domain within HMG-1, is a prerequisite for a preferential
      binding of the B domain to supercoiled DNA. The above sequence is also essential
      for a high-affinity binding of the B domain to DNA containing a site-specific
      major 1,2-d(GpG) intrastrand DNA adduct of cisplatin. Mutation of Arg(97), but
      not Lys(90) [Lys(90) forms a specific cross-link with platinum(II) in major
      groove of cisplatin-modified DNA; Kane, S. A., and Lippard, S. J. (1996)
      Biochemistry 35, 2180--2188], to alanine significantly (>40-fold) reduces
      affinity of the B domain to cisplatin-modified DNA, inhibits the ability of the B
      domain to bend (ligase-mediated circularization) or supercoil DNA, and results in
      a loss of the preferential binding of the B domain to supercoiled DNA without
      affecting the structural-specificity of the HMG-box for four-way DNA junctions.
      Some of the reported activities of the B domain are enhanced when the B domain is
      covalently linked to the A domain. We propose that binding of the A/B linker
      region within the major DNA groove helps the two HMG-1 domains to anchor to the
      minor DNA groove to facilitate their DNA binding and other activities.

PMID- 11294646
TI  - Multiple regions of subunit interaction in Drosophila mitochondrial DNA
      polymerase: three functional domains in the accessory subunit.
AB  - Drosophila mitochondrial DNA polymerase, pol gamma, is a heterodimeric complex of
      catalytic subunit and accessory subunits. Physical interactions between the two
      subunits were investigated by deletion mutagenesis in both in vivo reconstitution
      and in vitro protein overlay analyses. Our results suggest that the accessory
      subunit may consist of three domains, designated the N, M, and C domains. The M
      and C regions comprise the major contacts involved in subunit interaction, likely
      with multiple sites in the exonuclease (exo) region and part of the spacer
      between the exo and DNA polymerase (pol) regions in the catalytic subunit.
      Furthermore, the N region in the accessory subunit may modulate subunit assembly
      and/or conformation through weak interaction with the pol region in the catalytic
      subunit. Sequence comparisons identify a significant similarity between the M
      region of the accessory subunit and the RNase H domain of HIV-1 reverse
      transcriptase. On the basis of these results, the proposed function of the C
      terminus of the accessory subunit in RNA primer recognition, and previous
      observations that mitochondrial DNA polymerase is itself a reverse transcriptase,
      we propose that the overall conformation and arrangement of functional regions in
      the Drosophila pol gamma complex resemble those of HIV-1 reverse transcriptase.

PMID- 11294647
TI  - The cellular response to DNA damage induced by the enediynes C-1027 and
      neocarzinostatin includes hyperphosphorylation and increased nuclear retention of
      replication protein a (RPA) and trans inhibition of DNA replication.
AB  - This study examined the cellular response to DNA damage induced by antitumor
      enediynes C-1027 and neocarzinostatin. Treatment of cells with either agent
      induced hyperphosphorylation of RPA32, the middle subunit of replication protein
      A, and increased nuclear retention of RPA. Nearly all of the RPA32 that was not
      readily extractable from the nucleus was hyperphosphorylated, compared to < or
      =50% of the soluble RPA. Enediyne concentrations that induced RPA32
      hyperphosphorylation also decreased cell-free SV40 DNA replication competence in
      extracts of treated cells. This decrease did not result from damage to the DNA
      template, indicating trans-acting inhibition of DNA replication. Enediyne-induced
      RPA hyperphosphorylation was unaffected by the replication elongation inhibitor
      aphidicolin, suggesting that the cellular response to enediyne DNA damage was not
      dependent on elongation of replicating DNA. Neither recovery of replication
      competence nor reversal of RPA effects occurred when treated cells were further
      incubated in the absence of drug. C-1027 and neocarzinostatin doses that caused
      similar levels of DNA damage resulted in equivalent increases in RPA32
      hyperphosphorylation and RPA nuclear retention and decreases in replication
      activity, suggesting a common response to enediyne-induced DNA damage. By
      contrast, DNA damage induced by C-1027 was at least 5-fold more cytotoxic than
      that induced by neocarzinostatin.

PMID- 11294648
TI  - Purification and characterization of a Ca2+-independent endoprotease activity
      from peripheral blood lymphocytes: involvement in HIV-1 gp160 maturation.
AB  - We have analyzed the calcium requirement for HIV-1 gp160 processing in cultured
      nonlymphoid (CV-1 and HeLa-CD4) and human-lymphoid [Jurkat, Molt-4 and peripheral
      blood lymphocytes (PBMCs)] cells. The processing of gp160 in these cells,
      infected with recombinant vaccinia virus encoding the gp160 gene, was only
      partially affected by intracellular calcium depletion induced by the calcium
      ionophore A23187 and calcium chelator EGTA. These observations prompted us to
      purify the Ca(2+)-independent gp160 processing enzyme from natural targets of HIV
      1 PBMCs. The endoprotease was purified to homogeneity by the use of four
      chromatography fractionation steps and the constant detection of the Ca(2+)
      independent activity at each one of them. The enzyme was believed to be a
      membrane-associated heteromeric 120-kDa protein composed of three subunits of 66,
      32, and 24 kDa. It was found to be specifically inhibited by substrate analogues,
      decanoyl-RVKR-chloromethyl ketone, and serine protease inhibitors including
      diisopropyl fluorophosphate (DFP) and TLCK. In contrast, no effect was observed
      with reducing agents including 2-beta-mercaptoethanol, N-ethylmaleimide, L
      cysteine, and dithiothreitol. There were significant similarities between
      inhibition profiles of the purified enzyme in vitro and those of the endogenous
      endoprotease(s) in cell culture experiments. Therefore, the selectivity of
      purified endoprotease for the gp160 cleavage site, its requirement for additional
      residues around this consensus sequence, and its isolation from natural targets
      of HIV-1, made it a good candidate in the gp160 maturation process. We provide
      more direct and supporting evidence that HIV-1 gp160 maturation may involve at
      least two families of divergent endoproteases according to calcium dependence.

PMID- 11294649
TI  - Structural and functional consequences of inactivation of human glutathione S
      transferase P1-1 mediated by the catechol metabolite of equine estrogens, 4
      hydroxyequilenin.
AB  - The inactivation mechanism(s) of human glutathione S-transferase P1-1 (hGST P1-1)
      by the catechol metabolite of Premarin estrogens, 4-hydroxyequilenin (4-OHEN),
      was (were) studied by means of site-directed mutagenesis, electrospray ionization
      mass spectrometric analysis, titration of free thiol groups, kinetic studies of
      irreversible inhibition, and analysis of band patterns on nonreducing sodium
      dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE). The four
      cysteines (Cys 14, Cys 47, Cys 101, and Cys 169 in the primary sequence) in hGST
      P1-1 are susceptible to electrophilic attack and/or oxidative damage leading to
      loss of enzymatic activity. To investigate the role of cysteine residues in the 4
      OHEN-mediated inactivation of this enzyme, one or a combination of cysteine
      residues was replaced by alanine residues (C47A, C101A, C47A/C101A,
      C14A/C47A/C101A, and C47A/C101A/C169A mutants). Mutation of Cys 47 decreased the
      affinity for the substrate GSH but not for the cosubstrate 1-chloro-2,4
      dinitrobenzene (CDNB). However, the Cys 47 mutation did not significantly affect
      the rate of catalysis since V(max) values of the mutants were similar or higher
      compared to that of wild type. Electrospray ionization mass spectrometric
      analyses of wild-type and mutant enzymes treated with 4-OHEN showed that a single
      molecule of 4-OHEN-o-quinone attached to the proteins, with the exception of the
      C14A/C47A/C101A mutant where no covalent adduct was detected. 4-OHEN also caused
      oxidative damage as demonstrated by the appearance of disulfide-bonded species on
      nonreducing SDS--PAGE and protection of 4-OHEN-mediated enzyme inhibition by free
      radical scavengers. The studies of thiol group titration and irreversible kinetic
      experiments indicated that the different cysteines have distinct reactivity for 4
      OHEN; Cys 47 was the most reactive thiol group whereas Cys 169 was resistant to
      modification. These results demonstrate that hGST P1-1 is inactivated by 4-OHEN
      through two possible mechanisms: (1) covalent modification of cysteine residues
      and (2) oxidative damage leading to proteins inactivated by disulfide bond
      formation.

PMID- 11294650
TI  - Conformation of myosin interdomain interactions during contraction: deductions
      from muscle fibers using polarized fluorescence.
AB  - Myosin cross-bridge subfragment 1 (S1) is the ATP catalyzing motor protein in
      muscle. It consists of three domains that catalyze ATP and bind actin
      (catalytic), conduct energy transduction (converter), and transport the load
      (lever arm). Force development during contraction is thought to result from
      rotary lever arm movement with the cross-bridge attached to actin. To elucidate
      cross-bridge structure during force development, two crystal structures of S1
      were extrapolated to working "in solution" or oriented "in tissue" forms, using
      structure-sensitive optical spectroscopic signals from two extrinsic probes. The
      probes were located at two interfaces containing the catalytic, converter, and
      lever arm domains of S1. Observed signals included circular dichroism (CD) and
      absorption originating from S1 in solution in the presence and absence of actin
      and fluorescence polarization from cross-bridges in muscle fibers. Theoretical
      signals were calculated from S1 crystal structure models perturbed with lever arm
      movement from swiveling at three conserved glycines, 699, 703, and 710 (chicken
      skeletal myosin numbering). Best agreement between the computed and observed
      signals gave structures showing that actin binding to S1 causes movement of the
      lever arm. A three-state model of S1 conformation during contraction consists of
      three actin-bound cross-bridge states observed from muscle fibers in isometric
      contraction, in the presence of MgADP, and in rigor. Structures best representing
      these states show that most of the lever arm rotation occurs between isometric
      contraction and the MgADP states, i.e., during phosphate release. Smaller but
      significant lever arm rotation occurs with ADP dissociation. Structural changes
      within the S1 interfaces studied are discussed in the accompanying paper
      [Burghardt et al. (2001) Biochemistry 40, 4834-4843].

PMID- 11294651
TI  - Conformation of myosin interdomain interactions during contraction: deductions
      from proteins in solution.
AB  - Myosin subfragment 1 (S1) is the ATP catalyzing motor protein in muscle. It
      consists of three domains that catalyze ATP and bind actin (catalytic), conduct
      energy transduction (converter), and transport the load (lever arm). These
      domains interface in two places identified as interface I, containing the
      reactive thiol (SH1) and ATP-sensitive tryptophan (Trp510), and interface II,
      containing the reactive lysine residue (RLR). Two crystal structures of S1 were
      extrapolated to working "in solution" or oriented "in tissue" forms, using
      structure-sensitive optical spectroscopic signals from extrinsic probes located
      in the interfaces. Observed signals included circular dichroism (CD) and
      absorption originating from S1 in solution in the presence and absence of actin
      and fluorescence polarization from cross-bridges in muscle fibers. Theoretical
      signals were calculated from S1 crystal structure models perturbed with lever arm
      movement from swiveling at three conserved glycines, 699, 703, and 710 (chicken
      skeletal myosin numbering). Structures giving the best agreement between the
      computed and observed signals were selected as the representative forms. Both
      interfaces undergo dramatic conformational change during ATPase and force
      development. Changes at interface I suggest the molecular basis for the
      collisional quenching sensitivity of Trp510 to nucleotide binding. The probe
      conformation at SH1 suggests how it alters S1 ATPases. At interface II, the
      spatial relationship of the lever arm and the extrinsic probe at RLR suggests how
      the probe alters S1 ATPases and that it should inhibit lever arm movement during
      the power stroke. The latter possibility, if true, establishes a part of the
      corridor through which the lever arm swings during the power stroke. Global
      structural changes in actomyosin are discussed in the accompanying paper
      [Burghardt et al. (2001) Biochemistry 40, 4821-4833].

PMID- 11294652
TI  - Properties of microtubules assembled from mammalian tubulin synthesized in
      Escherichia coli.
AB  - When isolated from tissues, the alpha beta-dimeric protein tubulin consists of
      multiple isoforms which originate from the expression and subsequent
      posttranslational modification of multiple polypeptide sequences. Microtubules
      studied in vitro consist of mixtures of these isoforms. It is therefore not known
      whether dimers composed of single sequences of alpha- and beta-tubulin can
      polymerize to form microtubules, or whether posttranslational modifications may
      be necessary for microtubule assembly. To initiate investigation of these
      questions, rabbit reticulocyte lysate, which contains the cytoplasmic chaperonin
      CCT and its cofactors, was employed to prepare substantial quantities (tens of
      micrograms) of active tubulin by in vitro folding of mouse alpha- and beta
      tubulins recombinantly synthesized in E. coli. This recombinant tubulin is
      composed of only a single alpha-chain and a single beta-chain. When analyzed
      after folding by isoelectric focusing, each chain yielded only one band,
      indicating that neither was detectably posttranslationally modified in the course
      of the folding reaction. When subjected to assembly-promoting conditions, this
      tubulin formed microtubules without the addition of any exogenous protein.
      Electron microscopy showed them to be of normal morphology. Analysis of their
      protein composition showed that they are composed nearly entirely of recombinant
      tubulin. These results demonstrate that the naturally occurring mixtures of
      isoforms are not strictly required for the formation of microtubules. They also
      open a route to other studies, both biomedical and structural, of fully defined
      tubulin in vitro.

PMID- 11294653
TI  - Contribution of polar groups in the interior of a protein to the conformational
      stability.
AB  - It has been generally believed that polar residues are usually located on the
      surface of protein structures. However, there are many polar groups in the
      interior of the structures in reality. To evaluate the contribution of such
      buried polar groups to the conformational stability of a protein, nonpolar to
      polar mutations (L8T, A9S, A32S, I56T, I59T, I59S, A92S, V93T, A96S, V99T, and
      V100T) in the interior of a human lysozyme were examined. The thermodynamic
      parameters for denaturation were determined using a differential scanning
      calorimeter, and the crystal structures were analyzed by X-ray crystallography.
      If a polar group had a heavy energy cost to be buried, a mutant protein would be
      remarkably destabilized. However, the stability (Delta G) of the Ala to Ser and
      Val to Thr mutant human lysozymes was comparable to that of the wild-type
      protein, suggesting a low-energy penalty of buried polar groups. The structural
      analysis showed that all polar side chains introduced in the mutant proteins were
      able to find their hydrogen bond partners, which are ubiquitous in protein
      structures. The empirical structure-based calculation of stability change (Delta
      Delta G) [Takano et al. (1999) Biochemistry 38, 12698--12708] revealed that the
      mutant proteins decreased the hydrophobic effect contributing to the stability
      (Delta G(HP)), but this destabilization was recovered by the hydrogen bonds newly
      introduced. The present study shows the favorable contribution of polar groups
      with hydrogen bonds in the interior of protein molecules to the conformational
      stability.

PMID- 11294654
TI  - NMR solution studies of hamster galectin-3 and electron microscopic visualization
      of surface-adsorbed complexes: evidence for interactions between the N- and C
      terminal domains.
AB  - Galectin-3, a beta-galactoside binding protein, contains a C-terminal
      carbohydrate recognition domain (CRD) and an N-terminal domain that includes
      several repeats of a proline-tyrosine-glycine-rich motif. Earlier work based on a
      crystal structure of human galectin-3 CRD, and modeling and mutagenesis studies
      of the closely homologous hamster galectin-3, suggested that N-terminal tail
      residues immediately preceding the CRD might interfere with the canonical subunit
      interaction site of dimeric galectin-1 and -2, explaining the monomeric status of
      galectin-3 in solution. Here we describe high-resolution NMR studies of hamster
      galectin-3 (residues 1--245) and several of its fragments. The results indicate
      that the recombinant N-terminal fragment Delta 126--245 (residues 1--125) is an
      unfolded, extended structure. However, in the intact galectin-3 and fragment
      Delta 1--93 (residues 94--245), N-terminal domain residues lying between
      positions 94 and 113 have significantly reduced mobility values compared with
      those expected for bulk N-terminal tail residues, consistent with an interaction
      of this segment with the CRD domain. In contrast to the monomeric status of
      galectin-3 (and fragment Delta 1--93) in solution, electron microscopy of
      negatively stained and rotary shadowed samples of hamster galectin-3 as well as
      the CRD fragment Delta 1--103 (residues 104--245) show the presence of a
      significant proportion (up to 30%) of oligomers. Similar imaging of the N
      terminal tail fragment Delta 126--245 reveals the presence of fibrils formed by
      intermolecular interactions between extended polypeptide subunits.
      Oligomerization of substratum-adsorbed galectin-3, through N- and C-terminal
      domain interactions, could be relevant to the positive cooperativity observed in
      binding of the lectin to immobilized multiglycosylated proteins such as laminin.

PMID- 11294655
TI  - Probing site specificity of DNA binding metallointercalators by NMR spectroscopy
      and molecular modeling.
AB  - The molecular recognition of oligonucleotides by chiral ruthenium complexes has
      been probed by NMR spectroscopy using the template Delta-cis-alpha- and Delta-cis
      beta-[Ru(RR-picchxnMe(2)) (bidentate)](2+), where the bidentate ligand is one of
      phen (1,10-phenanthroline), dpq (dipyrido[3,2-f:2',3'-h]quinoxaline), or phi
      (9,10-phenanthrenequinone diimine) and picchxnMe(2)() is N,N'-dimethyl-N,N'-di(2
      picolyl)-1,2-diaminocyclohexane. By varying only the bidentate ligand in a series
      of complexes, it was shown that the bidentate alone can alter binding modes. DNA
      binding studies of the Delta-cis-alpha-[Ru(RR-picchxnMe(2))(phen)](2+) complex
      indicate fast exchange kinetics on the chemical shift time scale and a "partial
      intercalation" mode of binding. This complex binds to [d(CGCGATCGCG)](2) and
      [d(ATATCGATAT)](2) at AT, TA, and GA sites from the minor groove, as well as to
      the ends of the oligonucleotide at low temperature. Studies of the Delta-cis-beta
      [Ru(RR-picchxnMe(2))(phen)](2+) complex with [d(CGCGATCGCG)](2) showed that the
      complex binds only weakly to the ends of the oligonucleotide. The interaction of
      Delta-cis-alpha-[Ru(RR-picchxnMe(2))(dpq)](2+) with [d(CGCGATCGCG)](2) showed
      intermediate exchange kinetics and evidence of minor groove intercalation at the
      GA base step. In contrast to the phen and dpq complexes, Delta-cis-alpha- and
      Delta-cis-beta-[Ru(RR-picchxnMe(2))(phi)](2+) showed evidence of major groove
      binding independent of the metal ion configuration. DNA stabilization induced by
      complex binding to [d(CGCGATCGCG)](2) (measured as DeltaT(m)) increases in the
      order phen < dpq and DNA affinity in the order phen < dpq < phi. The groove
      binding preferences exhibited by the different bidentate ligands is explained
      with the aid of molecular modeling experiments.

PMID- 11294658
TI  - Complexity and power in case-control association studies.
AB  - A general method is described for estimation of the power and sample size of
      studies relating a dichotomous phenotype to multiple interacting loci and
      environmental covariates. Either a simple case-control design or more complex
      stratified sampling may be used. The method can be used to design individual
      studies, to evaluate the power of alternative test statistics for complex traits,
      and to examine general questions of study design through explicit scenarios. The
      method is used here to study how the power of association tests is affected by
      problems of allelic heterogeneity and to investigate the potential role for
      collective testing of sets of related candidate genes in the presence of locus
      heterogeneity. The results indicate that allele-discovery efforts are crucial and
      that omnibus tests or collective testing of alleles can be substantially more
      powerful than separate testing of individual allelic variants. Joint testing of
      multiple candidate loci can also dramatically improve power, despite model
      misspecification and inclusion of irrelevant loci, but requires an a priori
      hypothesis defining the set of loci to investigate.

PMID- 11294656
TI  - Structural and dynamic perturbations induced by heme binding in cytochrome b5.
AB  - The water-soluble domain of rat hepatic cytochrome b(5) undergoes marked
      structural changes upon heme removal. The solution structure of apocytochrome
      b(5) shows that the protein is partially folded in the absence of the heme group,
      exhibiting a stable module and a disordered heme-binding loop. The quality of the
      apoprotein structure in solution was improved with the use of heteronuclear NMR
      data. Backbone amide hydrogen exchange was studied to characterize cooperative
      units in the protein. It was found that this criterion distinguished the folded
      module from the heme-binding loop in the apoprotein, in contrast to the
      holoprotein. The osmolyte trimethylamine N-oxide (TMAO) did not affect the
      structure of the apoprotein in the disordered region. TMAO imparted a small
      stabilization consistent with an unfolded state effect correlating with the
      extent of buried surface area in the folded region of the native apoprotein. The
      failure of the osmolyte to cause large conformational shifts in the disordered
      loop supported the view that the specificity of the local sequence for the
      holoprotein fold was best developed with the stabilization of the native state
      through heme binding. To dissect the role of the heme prosthetic group in forcing
      the disordered region into the holoprotein conformation, the axial histidine
      belonging to the flexible loop (His63) was replaced with an alanine, and the
      structural properties of the protein with carbon-monoxide-ligated reduced iron
      were studied. The His63Ala substitution resulted in a protein with lower heme
      affinity but nevertheless capable of complete refolding. This indicated that the
      coordination bond was not necessary to establish the structural features of the
      holoprotein. In addition, the weak binding of the heme in this protein resulted
      in conformational shifts at a location distant from the binding site. The data
      suggested an uneven distribution of cooperative elements in the structure of the
      cytochrome.

PMID- 11294659
TI  - Paternal uniparental isodisomy of chromosome 20q--and the resulting changes in
      GNAS1 methylation--as a plausible cause of pseudohypoparathyroidism.
AB  - Heterozygous inactivating mutations in the GNAS1 exons (20q13.3) that encode the
      alpha-subunit of the stimulatory G protein (Gsalpha) are found in patients with
      pseudohypoparathyroidism type Ia (PHP-Ia) and in patients with pseudo
      pseudohypoparathyroidism (pPHP). However, because of paternal imprinting,
      resistance to parathyroid hormone (PTH)-and, sometimes, to other hormones that
      require Gsalpha signaling-develops only if the defect is inherited from a female
      carrier of the disease gene. An identical mode of inheritance is observed in
      kindreds with pseudohypoparathyroidism type Ib (PHP-Ib), which is most likely
      caused by mutations in regulatory regions of the maternal GNAS1 gene that are
      predicted to interfere with the parent-specific methylation of this gene. We
      report a patient with PTH-resistant hypocalcemia and hyperphosphatemia but
      without evidence for Albright hereditary osteodystrophy who has paternal
      uniparental isodisomy of chromosome 20q and lacks the maternal-specific
      methylation pattern within GNAS1. Since studies in the patient's fibroblasts did
      not reveal any evidence of impaired Gsalpha protein or activity, it appears that
      the loss of the maternal GNAS1 gene and the resulting epigenetic changes alone
      can lead to PTH resistance in the proximal renal tubules and thus lead to
      impaired regulation of mineral-ion homeostasis.

PMID- 11294660
TI  - Localization of the gene for distal hereditary motor neuronopathy VII (dHMN-VII)
      to chromosome 2q14.
AB  - Distal hereditary motor neuronopathy type VII (dHMN-VII) is an autosomal dominant
      disorder characterized by distal muscular atrophy and vocal cord paralysis. We
      performed a genomewide linkage search in a large Welsh pedigree with dHMN-VII and
      established linkage to chromosome 2q14. Analyses of a second family with dHMN-VII
      confirmed the location of the gene and provided evidence for a founder mutation
      segregating in both pedigrees. The maximum three-point LOD score in the combined
      pedigree was 7.49 at D2S274. Expansion of a polyalanine tract in Engrailed-1, a
      transcription factor strongly expressed in the spinal cord, was excluded as the
      cause of dHMN-VII.

PMID- 11294661
TI  - Use of drug resistance sequence data for the systematic detection of non-B human
      immunodeficiency virus type 1 (HIV-1) subtypes: how to create a sentinel site for
      monitoring the genetic diversity of HIV-1 at a country scale.
AB  - To assess the molecular epidemiology of human immunodeficiency virus type 1 (HIV
      1), a screening method was developed for identification of non-B subtypes from
      sequence data obtained for resistance testing. The method is based on the
      evaluation of the percentage of divergence of a given sequence from the reference
      B subtype HXB2. Analysis of 1720 reverse-transcriptase (RT) and 1824 protease
      sequences stored in a database allowed for the determination of a threshold level
      of divergence from HXB2 above which a non-B subtype could be unambiguously
      characterized regardless of the pattern of resistance mutations (>8.6% for RT;
      >10.8% for protease). This conclusion was validated by phylogenetic analysis of
      RT, protease, and env genes. Overall, 72 (4.2%) and 73 (4.0%) non-B sequences
      were identified in the RT and protease coding regions, respectively. This method
      allows for the rapid detection of non-B subtypes among retrospective, recent, and
      future RT and/or protease sequence databases.

PMID- 11294663
TI  - Long-term clinical outcome of human immunodeficiency virus-infected patients with
      discordant immunologic and virologic responses to a protease inhibitor-containing
      regimen.
AB  - Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected
      patients who began first-line protease inhibitor therapy in 1996, the outcome of
      42 patients with discrepant virologic and immunologic responses to antiretroviral
      treatment at 12 months was analyzed at 30 months of treatment. The incidence of
      AIDS-defining events and deaths (14%) in the group of patients with immunologic
      responses in the absence of a virologic response was higher than that in full
      responder patients (2%); yet, the incidence in this group was lower than that in
      patients with no immunologic response, despite a virologic response (21%), and
      was lower than that in patients without an immunologic or virologic response
      (67%; P<.0001, log-rank test). Differences in outcome were significant (relative
      risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were
      compared with those of responder patients. The results support the relevance of
      the CD4 cell marker over plasma HIV load for predicting clinical outcome in
      patients who do not achieve full immunologic and virologic responses.

PMID- 11294662
TI  - Residual human immunodeficiency virus (HIV) Type 1 RNA and DNA in lymph nodes and
      HIV RNA in genital secretions and in cerebrospinal fluid after suppression of
      viremia for 2 years.
AB  - Residual viral replication persists in a significant proportion of human
      immunodeficiency virus (HIV)-infected patients receiving potent antiretroviral
      therapy. To determine the source of this virus, levels of HIV RNA and DNA from
      lymphoid tissues and levels of viral RNA in serum, cerebrospinal fluid (CSF), and
      genital secretions in 28 patients treated for < or =2.5 years with indinavir,
      zidovudine, and lamivudine were examined. Both HIV RNA and DNA remained
      detectable in all lymph nodes. In contrast, HIV RNA was not detected in 20 of 23
      genital secretions or in any of 13 CSF samples after 2 years of treatment. HIV
      envelope sequence data from plasma and lymph nodes from 4 patients demonstrated
      sequence divergence, which suggests varying degrees of residual viral replication
      in 3 and absence in 1 patient. In patients receiving potent antiretroviral
      therapy, the greatest virus burden may continue to be in lymphoid tissues rather
      than in central nervous system or genitourinary compartments.

PMID- 11294664
TI  - Homeostasis of naive and memory T cell subpopulations in peripheral blood and
      lymphoid tissues in the context of human immunodeficiency virus infection.
AB  - To understand the nature of naive and memory T cell depletion in human
      immunodeficiency virus (HIV) immunopathogenesis, their homeostasis in peripheral
      blood (PB) and lymph node (LN) compartments of HIV-infected patients was
      examined. Although the percentage of naive CD4+ cells was higher in LN than in PB
      mononuclear cells (LNMC and PBMC, respectively), the memory cells were higher in
      PBMC than in LNMC. The ratio of naive:memory CD4+ cells from PB positively
      correlated with that in LNs and with the absolute CD4+ cell counts and recall
      antigen responses, and the ratio inversely correlated with the cellular virus
      load from the corresponding compartment. These findings indicate that although
      the pattern of naive and memory cells in the LN and PB compartments appear
      divergent, their relationship is nonrandom and is significant. The
      naive&rcolon;memory ratio in PB appears to reflect the lymphoid microenvironment
      and may potentially be useful as a surrogate marker for treatment efficacy and
      immune reconstitution.

PMID- 11294665
TI  - Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus
      Type 1 vaccine with or without gp120: a phase 2 study in higher- and lower-risk
      volunteers.
AB  - Live attenuated viral vectors that express human immunodeficiency virus (HIV)
      antigens are being developed as potential vaccines to prevent HIV infection. The
      first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55,
      and protease) was conducted in 435 volunteers with and without gp120 boosting, to
      expand the safety database and to compare the immunogenicity of the vector in
      volunteers who were at higher risk with that in volunteers at lower risk for HIV
      infection. Neutralizing antibodies to the MN strain were stimulated in 94% of
      volunteers given vCP205 plus gp120 and in 56% of volunteers given vCP205 alone.
      CD8(+) cytotoxic T lymphocyte cells developed at some time point in 33% of
      volunteers given vCP205, with or without gp120. Phase 3 field trials with these
      or similar vaccines are needed, to determine whether efficacy in preventing HIV
      infection or in slowing disease progression among vaccinees who become infected
      is associated with the level and types of immune responses that were induced by
      the vaccines in this study.

PMID- 11294666
TI  - Population-based incidence of pertussis among adolescents and adults, Minnesota,
      1995-1996.
AB  - To estimate the incidence of pertussis, a prospective study was done among
      members of a managed care organization in Minneapolis/St. Paul, Minnesota. Of 212
      patients 10-49 years old enrolled from January 1995 through December 1996, 8 were
      found to be culture positive, 10 were found to be positive by polymerase chain
      reaction assay, 13 had a > or =2-fold increase in IgG or IgA to pertussis toxin
      (PT), and 18 had IgG to PT in a single serum specimen > or =3 SD above the mean
      of an age-matched control group. At least 1 positive laboratory test result for
      pertussis infection was found in 27 (13%) patients, among whom the duration of
      cough illness was a median of 42 days (range, 27-66 days). On the basis of any
      positive laboratory result, the estimated annual incidence of pertussis was 507
      cases per 100,000 person-years (95% confidence interval, 307-706 cases).
      Bordetella pertussis infection may be a more common cause of cough illness among
      adolescents and adults than was recognized previously.

PMID- 11294667
TI  - Molecular epidemiology of Bordetella pertussis by pulsed-field gel
      electrophoresis profile: Cincinnati, 1989-1996.
AB  - Reported cases of pertussis have increased in the United States, with peaks
      occurring every few years. Bordetella pertussis isolates collected in Cincinnati
      from 1989 to 1996 were analyzed with pulsed-field gel electrophoresis (PFGE), to
      evaluate trends. Among 496 isolates, 30 PFGE profiles were identified; 32% were
      CYXXI-010, the profile that predominated each year. Eighteen profiles (198
      strains) were identified in 1989-1992, 20 profiles (197 strains) were identified
      during the 1993 epidemic, and 11 profiles (101 strains) were identified in 1994
      1996. From 1989 to 1996, among 42 patients, isolates from household members in 17
      (89%) of 19 households had concordant PFGE profiles. There was no association
      between PFGE profile and seasonality, age, and hospitalization or pneumonia in
      infants <1 year old. The 1993 epidemic was associated primarily with an increased
      prevalence of PFGE profiles that circulated before and after 1993, which suggests
      that the epidemic was due to factors other than the emergence of a novel B.
      pertussis strain.

PMID- 11294668
TI  - Human monocyte-derived insulin-like growth factor-2 enhances the infection of
      human arterial endothelial cells by Chlamydia pneumoniae.
AB  - It has been shown that infection of human endothelial cells by Chlamydia
      pneumoniae is enhanced by co-culturing endothelial cells with human monocytes and
      is mediated by monocyte-derived soluble factors. This study was conducted to
      identify the infectivity-enhancing factor. Serum-free conditioned medium of human
      monocytic cells was fractionated by ultrafiltration. The enhancing activity was
      found in the fraction in the molecular mass range between 5000 and 10,000 kDa.
      Recombinant human insulin-like growth factor (IGF)-1 or -2, with a molecular mass
      of 7500 kDa, was added to the culture medium of human endothelial cells for
      growing C. pneumoniae. Only IGF-2 enhanced C. pneumoniae growth. Pretreatment of
      the conditioned medium with a monoclonal antibody against IGF-2 blocked the
      enhancing activity. This suggests that the infectivity-enhancing factor is IGF-2
      and that paracrine interactions between monocytes and endothelial cells in vivo
      can induce secretory products and sustain infection with C. pneumoniae within
      atherosclerotic lesions.

PMID- 11294669
TI  - Cryptosporidium parvum-specific antibody responses among children residing in
      Milwaukee during the 1993 waterborne outbreak.
AB  - A major gastroenteritis outbreak among >400,000 residents of Milwaukee,
      Wisconsin, in April 1993 was attributed to Cryptosporidium parvum oocysts in
      drinking water. Plasma specimens obtained from children (6 months to 12 years
      old) for routine blood lead level surveillance March-May 1993 were assayed by
      ELISA for levels of IgG antibody against the immunodominant Triton-17 and 27-kDa
      C. parvum antigens. Over a 5-week period, the seroprevalence for antibodies to
      the 2 antigens increased from 15% to 82% and from 17% to 87%, respectively, in
      samples from children living in southern ZIP code areas (n=218), whereas smaller
      increases (20% to 43% and 22% to 46%, respectively) were noted among samples from
      children living in northern ZIP code areas (n=335; P<.0001). The results
      demonstrate that C. parvum infection was much more widespread than previously
      appreciated and confirm that infection was associated with residence in the area
      served by the southern water treatment plant.

PMID- 11294670
TI  - Mitigation of hookworm disease by immunization with soluble extracts of
      Ancylostoma ceylanicum.
AB  - Hookworms are a leading cause of anemia in developing countries, and a strategy
      aimed at reducing pathology caused by blood-feeding adult parasites would be a
      valuable addition to global control efforts. This article describes experiments
      designed to induce resistance to the major clinical sequelae (weight loss and
      anemia) of Ancylostoma ceylanicum hookworm infection in Syrian golden hamsters of
      the outbred LVG strain. Previously infected animals acquired long-lived
      resistance to weight loss and anemia caused by a secondary hookworm infection.
      Furthermore, transfer of pooled serum from twice-infected hamsters to animals
      undergoing a primary infection was associated with partial resistance to growth
      delay and anemia. Active vaccination of hamsters with soluble adult hookworm
      antigens emulsified in alum led to partial protection from hookworm-associated
      pathology in the absence of reductions in adult worm burden. This intriguing
      result may have important implications for human vaccine development.

PMID- 11294671
TI  - Regulatory interactions between iron and nitric oxide metabolism for immune
      defense against Plasmodium falciparum infection.
AB  - Iron chelation therapy of Plasmodium falciparum infection alleviates the clinical
      course of cerebral malaria in children. This study assessed the underlying
      mechanisms of this therapy. Cytokine stimulation of human (intestinal cell line
      DLD-1) or murine cells (murine macrophage cell line RAW 264.7) resulted in
      increased nitric oxide (NO) formation and decreased survival of plasmodia within
      cocultured human erythrocytes. The addition of desferrioxamine (DFO) before
      cytokine treatment increased both NO formation and parasite killing but had no
      effect in the presence of the inhibitor of NO formation, L-N6-(1-iminoethyl)
      lysine. Moreover, peroxynitrite, which is formed after chemical reaction of NO
      with superoxide, appears to be the principal effector molecule for macrophage
      mediated cytotoxicity toward P. falciparum, and interferon-gamma is a major
      regulatory cytokine for this process. The effect of DFO on the clearance of
      plasmodia appears to be due to enhanced generation of NO, rather than to
      limitation of iron availability to the parasite.

PMID- 11294672
TI  - Self-replicative RNA vaccines elicit protection against influenza A virus,
      respiratory syncytial virus, and a tickborne encephalitis virus.
AB  - In genetic vaccination, recipients are immunized with antigen-encoding nucleic
      acid, usually DNA. This study addressed the possibility of using the recombinant
      alpha virus RNA molecule, which replicates in the cytoplasm of transfected cells,
      as a novel approach for genetic vaccination. Mice were immunized with recombinant
      Semliki Forest virus RNA-encoding envelope proteins from one of 3 viruses:
      influenza A virus, a tickborne flavivirus (louping ill virus), or respiratory
      syncytial virus (RSV). Serologic analyses showed that antigen-specific antibody
      responses were elicited. IgG isotyping indicated that predominantly Th1 type
      immune responses were induced after immunization with RSV F protein-encoding RNA,
      which is relevant for protection against RSV infection. Challenge infection
      showed that RNA immunization had elicited significant levels of protection
      against the 3 model virus diseases.

PMID- 11294674
TI  - Human immunodeficiency virus Type 1 (HIV-1) plasma virus load and markers of
      immune activation among HIV-infected female sex workers with sexually transmitted
      diseases in Abidjan, Cote d'Ivoire.
AB  - Plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and markers of
      immune activation were compared among HIV-1-infected female sex workers (FSWs)
      with (n=112) and without (n=88) sexually transmitted diseases (STDs) in Abidjan,
      Cote d'Ivoire. After adjustment for CD4+ T cells, the median virus load was 2.5
      fold higher among HIV-seropositive FSWs with STDs than among those without an STD
      (P=.053). Median virus load was higher for FSWs with a genital ulcer (P=.052) or
      gonorrhoea (P=.058) than for FSWs without any STD. Median levels of markers of
      immune activation (CD38 and HLA-DR on CD8+ T cells, soluble tumor necrosis factor
      alpha receptor II, and beta(2)-microglobulin) tended to be elevated, albeit
      nonsignificantly, among FSWs in the STD group. These findings have important
      public health implications in elaborating strategies for decreasing disease
      progression and transmission of HIV among FSWs.

PMID- 11294673
TI  - Cytomegalovirus (CMV)-specific CD4+ T lymphocyte immune function in long-term
      survivors of AIDS-related CMV end-organ disease who are receiving potent
      antiretroviral therapy.
AB  - To better understand the relation of cytomegalovirus (CMV)-specific CD4+ T
      lymphocyte immunity and clinical outcome in AIDS-related CMV end-organ disease, 2
      patient groups were prospectively studied: patients recently diagnosed with
      active CMV end-organ disease and survivors of CMV retinitis who had responded to
      highly active antiretroviral therapy and had quiescent retinitis when anti-CMV
      therapy was discontinued. Most patients with active CMV disease had negative CMV
      specific CD4+ T lymphocyte responses at diagnosis, as measured by
      lymphoproliferation (7/7) or cytokine flow cytometry (3/5) assays. In contrast,
      all 10 subjects with quiescent retinitis and >150 absolute CD4+ T
      lymphocytes/microL whose anti-CMV therapy was discontinued during 6 months of
      follow-up had positive CMV-specific immune responses at least once by each assay.
      However, 6 of these 10 subjects also had negative CMV-specific immune responses >
      or =1 time. Such patients may be at risk for future CMV disease progression and
      should be closely monitored.

PMID- 11294675
TI  - Survival of patients with AIDS, after diagnosis of Pneumocystis carinii
      pneumonia, in the United States.
AB  - To examine survival after diagnosis of Pneumocystis carinii pneumonia (PCP) and
      factors associated with early death (during the month of or the month after
      diagnosis of PCP), data were analyzed from the Adult and Adolescent Spectrum HIV
      Disease project. Among 4412 patients with 5222 episodes of PCP during follow-up
      (1992-1998), survival at >1 month after diagnosis was 82%, and survival at > or
      =12 months after diagnosis was 47%; 12-month survival increased from 40% in 1992
      1993 to 63% in 1996-1998. By multiple logistic regression analysis, early death
      was associated with history of PCP (odds ratio [OR], 1.4), age 45-59 years (OR,
      1.9) or > or =60 years (OR, 3.7), and CD4 cell count of 0-24 cells/microL (< or
      =5 months before PCP; OR, 1.8) or 25-49 cells/microL (OR, 1.4) (P<.05).
      Concurrent prescription of combination antiretroviral therapy (OR, 0.2) and other
      antiretroviral therapy (OR, 0.4) was associated with surviving the early period.
      This study shows improved survival after diagnosis of PCP in recent years,
      despite emergence of antibiotic-resistant mutant P. carinii strains.

PMID- 11294676
TI  - Prevalence of the K76T mutation in the putative Plasmodium falciparum chloroquine
      resistance transporter (pfcrt) gene and its relation to chloroquine resistance in
      Mozambique.
AB  - K76T, a mutation in the Plasmodium falciparum chloroquine (CQ) resistance
      transporter protein, has been implicated in resistance to CQ. A modified 14-day
      in vivo test to estimate the CQ resistance level was done in southern Mozambique:
      21 (42%) of 50 subjects who completed the follow-up were CQ susceptible. Use of
      msa2-restriction fragment length polymorphism (RFLP) genotyping to differentiate
      new from recrudescent infections made little difference in the estimated
      prevalence of resistance. The K76T mutation prevalence was estimated by RFLP
      polymerase chain reaction and sequencing, and its relation to parasitological CQ
      resistance was explored on day 0 samples: 51 of 56 pretreatment samples presented
      the T76 codon, and it was present in 100% of children with parasitological
      resistance. T76 also was present in 18 of 23 subjects in whom the infection
      resolved after CQ treatment. These findings show a high prevalence of the K76T
      mutation among wild isolates but also suggest additional factors responsible for
      CQ resistance.

PMID- 11294677
TI  - Polymorphisms in the Plasmodium falciparum pfcrt and pfmdr-1 genes and clinical
      response to chloroquine in Kampala, Uganda.
AB  - The molecular mechanism of chloroquine resistance in Plasmodium falciparum
      remains uncertain. Polymorphisms in the pfcrt and pfmdr-1 genes have been
      associated with chloroquine resistance in vitro, although field studies are
      limited. In evaluations of known polymorphisms in parasites from patients with
      uncomplicated malaria in Kampala, Uganda, the presence of 8 pfcrt mutations and 2
      pfmdr-1 mutations did not correlate with clinical response to therapy with
      chloroquine. Most notably, the pfcrt lysine-->threonine mutation at position 76,
      which recently correlated fully with chloroquine resistance in vitro, was present
      in 100% of 114 isolates, of which about half were from patients who recovered
      clinically after chloroquine therapy. These results suggest that, although key
      pfcrt polymorphisms may be necessary for the elaboration of resistance to
      chloroquine in areas with high levels of chloroquine resistance, other factors,
      such as host immunity, may contribute to clinical outcomes.

PMID- 11294678
TI  - Tissue cytokine responses in canine visceral leishmaniasis.
AB  - To elucidate the local tissue cytokine response of dogs infected with Leishmania
      chagasi, cytokine mRNA levels were measured in bone marrow aspirates from 27
      naturally infected dogs from Brazil and were compared with those from 5
      uninfected control animals. Interferon-gamma mRNA accumulation was enhanced in
      infected dogs and was positively correlated with humoral (IgG1) but not with
      lymphoproliferative responses to Leishmania antigen in infected dogs. Increased
      accumulation of mRNA for interleukin (IL)-4, IL-10, and IL-18 was not observed in
      infected dogs, and mRNA for these cytokines did not correlate with antibody or
      proliferative responses. However, infected dogs with detectable IL-4 mRNA had
      significantly more severe symptoms. IL-13 mRNA was not detectable in either
      control or infected dogs. These data suggest that clinical symptoms are not due
      to a deficiency in interferon-gamma production. However, in contrast to its role
      in human visceral leishmaniasis, IL-10 may not play a key immunosuppressive role
      in dogs.

PMID- 11294679
TI  - Neutralizing antiviral antibodies reduce hematogenic viral spread but not
      antiviral cytotoxic T cell induction and subsequent immunopathology.

PMID- 11294681
TI  - Timing of human immunodeficiency virus type 1 and human herpesvirus 8 infections
      and length of the Kaposi's sarcoma-free period in coinfected persons.

PMID- 11294682
TI  - No increase in liver decompensation risk with atypical hepatitis C virus antibody
      pattern.

PMID- 11294683
TI  - A pathologist's view of organisms and human atherosclerosis.

PMID- 11294684
TI  - Effects of balloon mitral valvuloplasty on systemic and regional left atrial
      levels of prothrombin fragment 1+2 in mitral stenosis.

PMID- 11294686
TI  - Gender differences in vascular function: time to look beyond oestrogen and NO?

PMID- 11294687
TI  - Gender differences in protein kinase G-mediated vasorelaxation of rat aorta.
AB  - Although gender and oestrogen treatment influence production of the vasorelaxant,
      NO, their influence on factors downstream in the NO signal-transduction pathway,
      specifically protein kinase G (PKG), remains unknown. We aimed to study the
      influence of sex hormones on PKG, along with the endothelial modulation of these
      effects, in rat thoracic aortic rings in two separate groups, control male and
      female rats and ovariectomized female rats after treatment with oestrogen or
      vehicle. Vessel preparations were preconstricted with phenylephrine (0.1 microM).
      Constrictions were greater in male than female aortas. This differential effect
      was attenuated by endothelium removal, addition of the guanylate cyclase
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM) and the
      nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100
      microM), supporting the role of NO in maintenance of basal relaxation and
      vascular tone in females. We have examined the relative activity of the specific
      PKG subtypes 1 alpha and 1 beta in vascular smooth muscle, based on relaxation of
      rat aortas by two cGMP analogues with different selectivity, beta-phenyl-l-N(2)
      ethano-8-bromo-cGMP (8-Br-PET-cGMP) and 8-(2-aminophenylthio)cGMP (8-APT-cGMP). 8
      Br-PET-cGMP was more potent than 8-APT-cGMP in both sexes, suggesting that PKG 1
      alpha is the primary subtype involved in vasorelaxation. The gender differences
      in PKG activity were examined based on relaxation responses in male and female
      rat aortas. Both 8-Br-PET-cGMP and 8-APT-cGMP were more potent in aortas from
      male than female rats. In further studies on the endothelial modulation of
      relaxation with 8-APT-cGMP, the differential gender-vasorelaxation response was
      negated by endothelium removal and addition of the guanylate cyclase inhibitor
      ODQ (1 microM), but not by the NOS inhibitor L-NMMA (100 microM), suggesting that
      an endothelial-dependent factor other than NO may be responsible for the observed
      differential PKG-mediated vasorelaxation between the sexes. To further
      investigate oestrogen influence on PKG, treated female rats were studied.
      Contrary to our hypothesis, in the presence of 1 microM ODQ, there were no
      differences in either the phenylephrine constriction, or the relaxation with 8
      APT-cGMP from either sham-operated, vehicle-treated or oestrogen-treated
      ovariectomized rats. In conclusion, female rat aortas have greater basal NO
      production compared with males. Relaxant responses to PKG activation are greater
      in aortas from male compared with female rats. These findings suggest hormonal
      regulation of PKG; however, oestrogen treatment of ovariectomized rats did not
      affect PKG activity, suggesting factors other than oestrogen may be responsible
      for the gender differences noted in this study.

PMID- 11294688
TI  - Angiotensin receptors: distribution, signalling and function.
AB  - Angiotensin II (Ang II) is a multi-functional hormone that plays a major role in
      regulating blood pressure and cardiovascular homoeostasis. The actions of Ang II
      are mediated by at least two receptor subtypes, designated AT(1) and AT(2). In
      addition, other angiotensin receptors have been identified which may recognize
      other angiotensin peptide fragments; however, until now only the AT(1) and AT(2)
      receptor have been cloned in animals or humans. Most of the well-described
      actions of Ang II, such as vasoconstriction, facilitation of sympathetic
      transmission, stimulation of aldosterone release and promotion of cellular growth
      are all mediated by the AT(1) receptor. Much less is known about the function of
      the AT(2) receptor, but recent studies suggest that it may play a role in
      mediating anti-proliferation, cellular differentiation, apoptosis and
      vasodilatation. In this review, we discuss recent advances in our understanding
      of Ang II receptors, in particular, their distribution, signalling and function.

PMID- 11294689
TI  - Carbohydrate and fat have different effects on plasma leptin concentrations and
      adipose tissue leptin production.
AB  - Leptin is secreted by adipocytes and plays a role in the regulation of food
      intake. However, the regulation of leptin production by adipose tissue is
      unclear. We have investigated whether a mixed meal or a high-fat load given
      orally, or a pure fat load given intravenously, stimulates adipose tissue leptin
      production. Six volunteers were studied on two occasions following an overnight
      fast. On one occasion they consumed tomato soup containing 40 g of
      triacylglycerol (as Intralipid) and 9.6 g of carbohydrate; on the other occasion
      Intralipid was infused intravenously over 4 h to give the same fat load. A
      further eight subjects consumed a mixed meal (containing 37 g of fat and 100 g of
      carbohydrate) after an overnight fast. Paired blood samples were obtained from an
      arterialized hand vein and a vein draining subcutaneous adipose tissue at
      baseline and for 6 h following the meals or the start of the infusion. After both
      the intravenous and oral fat loads, the arterialized and adipose venous plasma
      leptin concentrations decreased over 6 h (both P<0.001), as did the leptin veno-
      arterial difference (P=0.01). Following the mixed meal, there was a slight
      increase in the arterialized plasma leptin concentration (P=0.02) and a more
      marked increase in the adipose venous plasma leptin concentration (P=0.03) and in
      the adipose tissue leptin veno--arterial difference (P=0.01), all peaking at 240
      min. We conclude that the increase in plasma leptin concentration observed after
      meals is not simply a result of an energy load, but is in response to a signal
      that is not present following a fat load without carbohydrate.

PMID- 11294691
TI  - Radial artery hypertrophy occurs in coronary atherosclerosis and is independent
      of blood pressure.
AB  - Endothelial dysfunction, believed to underlie the structural changes of
      atherosclerosis, is a systemic phenomenon. Despite this, the radial artery has
      been considered as devoid of atherosclerosis and is commonly used as a conduit in
      coronary artery bypass grafting (CABG). Recently, histological study has shown
      intimal hyperplasia and other structural changes consistent with early
      atherosclerosis in the radial artery. The objective of the present study was to
      determine if structural changes in the radial artery could be detected in vivo in
      patients with coronary atherosclerosis. Using high resolution echo-tracking,
      measurements of radial artery internal diameter, wall thickness and wall cross
      sectional area were made in 25 patients awaiting CABG and in 20 controls. Digital
      and brachial blood pressures were also recorded. Mean arterial pressures did not
      differ between the patient and control groups. All measures of wall thickness
      were greater in the patient than the control group. Neither current arterial
      pressures nor past history of hypertension correlated with wall thickness. Using
      a model of analysis of covariance, coronary artery disease was the best single
      predictor of intima-media thickness, R(2)=48%, n=44, P<0.0005. We concluded that
      increased radial artery wall thickness can be demonstrated in vivo in patients
      with coronary atherosclerosis. This is a novel observation which seems to be
      independent of blood pressure, and is consistent both with the hypothesis of
      systemic endothelial dysfunction leading to systemic structural changes and also
      to the recent histological evidence for atherosclerotic changes in this vessel.

PMID- 11294690
TI  - Increased levels of typically fetal bile acid species in patients with
      hepatocellular carcinoma.
AB  - The aim of this work was to investigate the reappearance during liver neoplasia
      of bile acids (BAs) species, which are unusual in healthy adults, but common in
      fetuses. Serum and urine samples were collected from patients with hepatocellular
      carcinoma (HCC; n=27), and for comparative purposes, with liver cirrhosis (n=49),
      liver metastasis (n=19), chronic viral hepatitis (n=11) and healthy volunteer
      (control group; n=26) groups. BAs were identified and measured by GC--MS.
      Hypercholanaemia was found in all groups of patients. In HCC, this was
      characterized by a marked increase in the chenodeoxycholate/cholate ratio in both
      serum and urine. Although increased levels of BAs, with hydroxylations at unusual
      positions, and oxo-BAs were found in HCC, these were not significantly different
      from those observed in other groups. However, BAs with a flat structure, i.e.
      Delta(4)-unsaturated- and 5 alpha- or allo-BAs, which were almost absent in
      healthy subjects, were markedly increased in the serum and urine of HCC patients.
      They were also detected, although in much lower amounts, in liver metastasis and
      liver cirrhosis, but not in viral hepatitis. Flat-BAs were better detected in
      urine than in serum. Urinary Delta(4)-unsaturated-BA output was significantly
      lower in patients with small tumours (<3 cm) compared with those with higher size
      tumours. No correlation between flat-BA output into urine and serum alpha
      fetoprotein or total BAs was found. These results suggest that Delta(4)- and/or
      allo-BAs are particularly elevated in patients with HCC, which may be a
      potentially useful complementary, rather than alternative, marker for early
      detection of liver neoplasia.

PMID- 11294692
TI  - Effects of prior moderate exercise on exogenous and endogenous lipid metabolism
      and plasma factor VII activity.
AB  - Moderate exercise reduces postprandial triacylglycerol concentrations, which are
      a risk marker for coronary heart disease. The present study sought to determine
      the qualitative nature of exercise-induced changes in lipid metabolism and their
      association (if any) with changes in factor VII activation. Eleven
      normotriglyceridaemic men, aged 51.7+/-6.1 years (mean+/-S.D.), participated in
      two oral fat tolerance tests after different pre-conditions: control (no
      exercise), and exercise (90 min of brisk walking the day before). Venous blood
      samples were obtained in the fasted state and for 8 h after ingestion of a high
      fat meal (1.32 g of fat, 1.36 g of carbohydrate, 0.30 g of protein and 10 mg of
      [1,1,1-(13)C] tripalmitin x kg(-1) body mass). Prior exercise reduced
      postprandial plasma triacylglycerol concentrations by 25+/-3% (mean+/-S.E.M.),
      with lower concentrations in the Svedberg flotation rate (Sf) 20--400 (very-low
      density lipoprotein) fraction accounting for 79+/-10% of this reduction. There
      was no effect on plasma factor VII coagulant activity or on the concentration of
      the active form of factor VIIa. Prior exercise increased postprandial serum 3
      hydroxybutyrate and plasma fatty acid concentrations, decreased serum
      postprandial insulin concentrations and increased exogenous (8 h (13)C breath
      excretion of 15.1+/-0.9% of ingested dose compared with 11.9+/-0.8%; P=0.00001)
      and endogenous postprandial fat oxidation. These data raise the possibility that
      reduced hepatic secretion of very-low-density lipoprotein plays a role in the
      attenuation of plasma triacylglycerol concentrations seen after exercise,
      although it is possible that increased triacylglycerol clearance also contributes
      to this effect.

PMID- 11294693
TI  - Left ventricular performance during prolonged exercise: absence of systolic
      dysfunction.
AB  - We assessed left ventricular systolic and diastolic performance during and after
      prolonged exercise under controlled conditions in a group of healthy, trained
      men. Previous studies have examined the effects of prolonged effort on left
      ventricular function, yet it remains unclear whether or not left ventricular
      dysfunction (e.g. cardiac fatigue) can be produced under such conditions. We
      studied 15 healthy men, aged 27+/-1 years (mean+/-S.E.M.). Subjects exercised on
      bicycles at a constant work rate (60% of maximum oxygen uptake per min) for 150
      min. Measurements of gas exchange, blood pressure and haematocrit were obtained,
      concurrent with the assessment of left ventricular function using equilibrium
      radionuclide angiography, at rest, during exercise (every 30 min) and after 30
      min of recovery. Fluid replacement was provided and monitored during the exercise
      period. The baseline resting and exercise ejection fractions were 66+/-2% and
      78+/-2% respectively. During exercise, subjects consumed 1816+/-136 ml of fluid,
      and the haematocrit had increased at 120 min of exercise (from 47.2%+/-0.6 to
      49.9+/-0.8%; P<0.05). There was no change in either systolic or diastolic blood
      pressure throughout the exercise period, but heart rate drifted upwards from
      141+/-2 beats/min after 30 min to 154+/-3 beats/min after 150 min (P<0.05). There
      was a small decline (8%; P<0.05) in end-diastolic volume at 150 min. No changes
      were observed in left ventricular ejection fraction, the pressure/volume ratio or
      end-systolic volume. After 30 min of sitting in recovery, heart rate was still
      higher than the pre-exercise value (84+/-3 compared with 69+/-2 beats/min;
      P<0.05), as were measures of peak filling rate and time to peak filling (P<0.05).
      The ejection fraction in the post-exercise recovery period was similar to the pre
      exercise value. The results indicate that prolonged exercise of moderate duration
      may not induce abnormal left ventricular systolic function or cardiac fatigue
      during exercise.

PMID- 11294694
TI  - Relationship between right-to-left shunts and cutaneous decompression illness.
AB  - The presence of a large right-to-left shunt is associated with neurological
      decompression illness after non-provocative dives, as a result of paradoxical gas
      embolism. A small number of observations suggest that cutaneous decompression
      illness is also associated with a right-to-left shunt, although an embolic
      aetiology of a diffuse rash is more difficult to explain. We performed a
      retrospective case--control comparison of the prevalence and sizes of right-to
      left shunts determined by contrast echocardiography performed blind to history in
      60 divers and one caisson worker with a history of cutaneous decompression
      illness, and 123 historical control divers. We found that 47 (77.0%) of the 61
      cases with cutaneous decompression illness had a shunt, compared with 34 (27.6%)
      of 123 control divers (P<0.001). The size of the shunts in the divers with
      cutaneous decompression illness was significantly greater than in the controls.
      Thus 30 (49.2%) of the 61 cases with cutaneous decompression illness had a large
      shunt at rest, compared with six (4.9%) of the 123 controls (P<0.001). During
      closure procedures in 17 divers who had cutaneous decompression illness, the mean
      diameter of the foramen ovale was 10.9 mm. Cutaneous decompression illness
      occurred after dives that were provocative or deep in subjects without shunts,
      but after shallower and non-provocative dives in those with shunts. The latter
      individuals are at increased risk of neurological decompression illness. We
      conclude that cutaneous decompression illness has two pathophysiological
      mechanisms. It is usually associated with a large right-to-left shunt, when the
      mechanism is likely to be paradoxical gas embolism with peripheral amplification
      when bubble emboli invade tissues supersaturated with nitrogen. Cutaneous
      decompression illness can also occur in individuals without a shunt. In these
      subjects, the mechanism might be bubble emboli passing through an 'overloaded'
      lung filter or autochthonous bubble formation.

PMID- 11294695
TI  - Selenite protects human endothelial cells from oxidative damage and induces
      thioredoxin reductase.
AB  - The ability of selenium to protect cultured human coronary artery endothelial
      cells (HCAEC), human umbilical vein endothelial cells (HUVEC) and bovine aortic
      endothelial cells (BAEC) from oxidative damage induced by 100 microM t-butyl
      hydroperoxide (t-BuOOH) was compared. Preincubation of human endothelial cells
      for 24 h with sodium selenite at concentrations as low as 5 nM provided
      significant protection against the harmful effects of 100 microM t-BuOOH, with
      complete protection being achieved with 40 nM selenite. The preincubation period
      was required for selenite to exert this protective effect on endothelial cells.
      When compared with selenium-deficient cells, the activities of cytoplasmic
      glutathione peroxidase (GPX-1), phospholipid hydroperoxide glutathione peroxidase
      (GPX-4) and thioredoxin reductase (TR) were each induced approx. 3--4-fold by 40
      nM selenite. HCAEC and HUVEC showed great similarity in their relative abilities
      to resist oxidative damage in the presence and absence of selenite, and the
      activities of TR and the GPXs were also similar in these cell types. BAEC were
      more susceptible to damage by 100 microM t-BuOOH than were human endothelial
      cells, and could not be protected completely by incubation with selenite at
      concentrations up to 160 nM. The activity of TR in human endothelial cells was
      approx. 25-fold greater than that in BAEC of a similar selenium status, but GPX-1
      and GPX-4 activities were not significantly different between the human and
      bovine cells. These studies, although performed with a small number of cultures,
      show for the first time that selenium at low doses can provide significant
      protection of the human coronary artery endothelium against damage by oxidative
      stress. TR may be an important antioxidant selenoprotein in this regard, in
      addition to the GPXs. The data also suggest that HUVEC, but not BAEC, represent a
      suitable model system in which to study the effects of selenium on the
      endothelium of human coronary arteries.

PMID- 11294696
TI  - Influence of an inducible nitric oxide synthase promoter variant on clinical
      variables in patients with coronary artery disease.
AB  - Pathophysiological processes in coronary artery disease (CAD) are influenced by
      genetic factors. Since (i) inducible nitric oxide synthase (iNOS) has important
      cardiovascular effects, and (ii) the promoter of the iNOS gene (NOS2A) is
      genetically modulated by a 4 bp insertion/deletion (+/-) polymorphism located 0.7
      kb upstream, we decided to examine the influence of this variant on clinical
      variables in 856 CAD patients of Anglo-Celtic/Northern European extraction. We
      found that 2% of CAD patients were homozygous for the + allele, and 19% were
      heterozygous. Males made up 74% of the patient group, and in these the + allele
      was associated with 38% higher plasma glucose levels (P=0.005), a 4.8% elevation
      in the waist/hip ratio (P=0.009) and a 48% greater frequency of unstable angina
      (P=0.014). The + allele, by influencing iNOS expression, could thus contribute to
      indices of insulin resistance and angina severity in male CAD patients.

PMID- 11294697
TI  - Neurohormonal activation, the renal dopaminergic system and sodium handling in
      patients with severe heart failure under vasodilator therapy.
AB  - The benefits of tailoring therapy with vasodilators in patients with severe heart
      failure are well documented, but this may lead to neurohormonal activation and
      sodium retention. Renal dopamine has local natriuretic actions and interacts with
      other hormones involved in renal sodium handling. The aim of the present work was
      to determine the effects of arterial underfilling induced by vasodilator therapy
      on renal sodium handling, neurohormonal activation and the activity of the renal
      dopaminergic system in patients with severe heart failure. For this purpose we
      monitored haemodynamic parameters, plasma levels of type B natriuretic peptide
      (BNP), catecholamines, aldosterone, renin activity (PRA), sodium and creatinine,
      and urinary excretion of sodium, creatinine, L-DOPA, dopamine and its
      metabolites, before initiation of sodium nitroprusside therapy and every 6 h
      thereafter (for 42 h), and again after 5 days of angiotensin-converting enzyme
      (ACE) inhibition, in 10 male patients with severe heart failure. The results of
      nitroprusside therapy were a marked increase in cardiac index and a substantial
      decrease in systemic vascular resistance index. Plasma levels of BNP decreased
      significantly, while PRA, noradrenaline and aldosterone showed marked increases,
      resulting in a substantial reduction in urinary sodium excretion. Creatinine
      clearance was not affected. Urinary dopamine and dopamine metabolites increased
      in response to nitroprusside therapy. After 5 days of ACE inhibition, urinary
      sodium returned to baseline values, while urinary dopamine was markedly reduced.
      These results suggest that the renal dopaminergic system is activated in patients
      with severe heart failure by stimuli leading to sodium renal reabsorption.

PMID- 11294698
TI  - Measurement of free and complexed soluble vascular endothelial growth factor
      receptor, Flt-1, in fluid samples: development and application of two new
      immunoassays.
AB  - Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis
      and enhances vascular permeability. VEGF interacts with the endothelium via two
      membrane-spanning receptors, fms-like tyrosine kinase (Flt)-1 and kinase domain
      receptor. A soluble form of Flt-1 (sFlt-1) was isolated from endothelial cell
      media; however, its biological significance is still unknown, with limited data
      on plasma sFlt-1 levels in disease states. We have developed two new ELISAs for
      detecting free and VEGF-complexed sFlt-1, which were tested in accordance with
      standard validation and assessment methodologies employed in commercial settings.
      The intra-and inter-assay coefficients of variation are <5% and 10% respectively,
      and results are highly reproducible. Applying these ELISAs in a clinical setting,
      we measured levels of VEGF, free and complexed sFlt-1 in citrated plasma from 40
      patients with cardiovascular disease and 40 healthy controls. Median
      (interquartile range) plasma levels of VEGF in patients were significantly
      greater than controls [403 pg/ml (158--925 pg/ml) versus 113 pg/ml (33--231
      pg/ml), P< or =0.05]. Free sFlt-1 was significantly lower in patients compared
      with controls [8 ng/ml (2--22 ng/ml) versus 21 ng/ml (10--73 ng/ml), P< or
      =0.05]. There was no significant difference in the levels of complexed sFlt-1
      between the two groups. Plasma levels of VEGF-complexed sFlt-1 are minimal,
      despite the presence of excess free sFlt-1. Thus unbound plasma VEGF detected by
      ELISA may represent the majority of circulating VEGF, and justifies the
      measurement of plasma VEGF as an indicator of circulating VEGF levels.
      Furthermore, these results suggest that circulating sFlt-1 may serve as a
      selective inhibitor of VEGF activity, and that this regulatory mechanism may be
      altered by pathological conditions.

PMID- 11294699
TI  - Infection control and changing health-care delivery systems.
AB  - In the past, health care was delivered mainly in acute-care facilities. Today,
      health care is delivered in hospital, outpatient, transitional care, long-term
      care, rehabilitative care, home, and private office settings. Measures to reduce
      health-care costs include decreasing the number of hospitals and the length of
      patient stays, increasing outpatient and home care, and increasing long-term care
      for the elderly. The home-care industry and managed care have become major
      providers of health care. The role of specialists in health-care epidemiology has
      changed accordingly.

PMID- 11294700
TI  - The impact of hospital-acquired bloodstream infections.
AB  - Nosocomial bloodstream infections are a leading cause of death in the United
      States. If we assume a nosocomial infection rate of 5%, of which 10% are
      bloodstream infections, and an attributable mortality rate of 15%, bloodstream
      infections would represent the eighth leading cause of death in the United
      States. Because most risk factors for dying after bacteremia or fungemia may not
      be changeable, prevention efforts must focus on new infection-control technology
      and techniques.

PMID- 11294701
TI  - The changing epidemiology of Staphylococcus aureus?
AB  - Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been
      largely confined to hospitals and long-term care facilities, are emerging in the
      community. The changing epidemiology of MRSA bears striking similarity to the
      emergence of penicillinase-mediated resistance in S. aureus decades ago. Even
      though the origin (hospital or the community) of the emerging MRSA strains is not
      known, the prevalence of these strains in the community seems likely to increase
      substantially.

PMID- 11294702
TI  - Emergence of vancomycin-resistant enterococci.
AB  - Vancomycin and ampicillin resistance in clinical Enterococcus faecium strains has
      developed in the past decade. Failure to adhere to strict infection control to
      prevent the spread of these pathogens has been well established. New data
      implicate the use of specific classes of antimicrobial agents in the spread of
      vancomycin-resistant enterococci (VRE). Extended-spectrum cephalosporins and
      drugs with potent activity against anaerobic bacteria may promote infection and
      colonization with VRE and may exert different effects on the initial
      establishment and persistence of high-density colonization. Control of VRE will
      require better understanding of the mechanisms by which different classes of
      drugs promote gastrointestinal colonization.

PMID- 11294703
TI  - Controlling antimicrobial resistance in hospitals: infection control and use of
      antibiotics.
AB  - Antimicrobial-drug resistance in hospitals is driven by failures of hospital
      hygiene, selective pressures created by overuse of antibiotics, and mobile
      genetic elements that can encode bacterial resistance mechanisms. Attention to
      hand hygiene is constrained by the time it takes to wash hands and by the adverse
      effects of repeated handwashing on the skin. Alcohol-based hand rubs can overcome
      the time problem and actually improve skin condition. Universal glove use could
      close gaps left by incomplete adherence to hand hygiene. Various interventions
      have been described to improve antibiotic use. The most effective have been
      programs restricting use of antibiotics and computer-based order forms for health
      providers.

PMID- 11294704
TI  - Impact of hospital care on incidence of bloodstream infection: the evaluation of
      processes and indicators in infection control study.
AB  - The Evaluation of Processes and Indicators in Infection Control (EPIC) study
      assesses the relationship between hospital care and rates of central venous
      catheter-associated primary bacteremia in 54 intensive-care units (ICUs) in the
      United States and 14 other countries. Using ICU rather than the patient as the
      primary unit of statistical analysis permits evaluation of factors that vary at
      the ICU level. The design of EPIC can serve as a template for studies
      investigating the relationship between process and event rates across health-care
      institutions.

PMID- 11294705
TI  - New technologies to prevent intravascular catheter-related bloodstream
      infections.
AB  - Most intravascular catheter-related infections are associated with central venous
      catheters. Technologic advances shown to reduce the risk for these infections
      include a catheter hub containing an iodinated alcohol solution, short-term
      chlorhexidine-silver sulfadiazine- impregnated catheters, minocycline-rifampin
      impregnated catheters, and chlorhexidine- impregnated sponge dressings.
      Nontechnologic strategies for reducing risk include maximal barrier precautions
      during catheter insertion, specialized nursing teams, continuing quality
      improvement programs, and tunneling of short-term internal jugular catheters.

PMID- 11294707
TI  - Preventing infections in non-hospital settings: long-term care.
AB  - Infection concerns in long-term care facilities include endemic infections,
      outbreaks, and colonization and infection with antimicrobial-drug resistant
      microorganisms. Infection control programs are now used in most long-term care
      facilities, but their impact on infections has not been rigorously evaluated.
      Preventive strategies need to address the changing complexity of care in these
      facilities, e.g., the increased use of invasive devices. The anticipated increase
      in the elderly population in the next several decades makes prevention of
      infection in long-term care facilities a priority.

PMID- 11294706
TI  - Ventilator-associated pneumonia or not? Contemporary diagnosis.
AB  - Ventilator-associated pneumonia (VAP) is pneumonia in patients who have been on
      mechanical ventilation for > or =48 hours. VAP is most accurately diagnosed by
      quantitative culture and microscopy examination of lower respiratory tract
      secretions, which are best obtained by bronchoscopically directed techniques such
      as the protected specimen brush and bronchoalveolar lavage. These techniques have
      acceptable repeatability, and interpretation of results is unaffected by
      antibiotics administered concurrently for infection at extrapulmonary sites as
      long as antimicrobial therapy has not been changed for <72 hours before
      bronchoscopy.

PMID- 11294708
TI  - Infection control in home care.
AB  - Although home care has expanded in scope and intensity in the United States in
      the past decade, infection surveillance, prevention, and control efforts have
      lagged behind. Valid and reliable definitions and methods for surveillance are
      needed. Prevention and control efforts are largely based upon acute-care
      practices, many of which may be unnecessary, impractical, and expensive in a home
      setting. Infectious disease control principles should form the basis of training
      home- care providers to assess infection risk and develop prevention strategies.

PMID- 11294709
TI  - Automated methods for surveillance of surgical site infections.
AB  - Automated data, especially from pharmacy and administrative claims, are available
      for much of the U.S. population and might substantially improve both inpatient
      and postdischarge surveillance for surgical site infections complicating selected
      procedures, while reducing the resources required. Potential improvements include
      better sensitivity, less susceptibility to interobserver variation, more uniform
      availability of data, more precise estimates of infection rates, and better
      adjustment for patients' coexisting illness.

PMID- 11294710
TI  - New surgical techniques and surgical site infections.
AB  - Technologic advances in surgery include a trend toward less invasive procedures,
      driven by potential benefits to patients and by health-care economics. These less
      invasive procedures provide infection control personnel opportunities for direct
      involvement in outcomes measurement.

PMID- 11294711
TI  - Preventing surgical site infections: a surgeon's perspective.
AB  - Wound site infections are a major source of postoperative illness, accounting for
      approximately a quarter of all nosocomial infections. National studies have
      defined the patients at highest risk for infection in general and in many
      specific operative procedures. Advances in risk assessment comparison may involve
      use of the standardized infection ratio, procedure-specific risk factor
      collection, and logistic regression models. Adherence to recommendations in the
      1999 Centers for Disease Control and Prevention guidelines should reduce the
      incidence of infection in surgical patients.

PMID- 11294712
TI  - Hygiene of the skin: when is clean too clean?
AB  - Skin hygiene, particularly of the hands, is a primary mechanism for reducing
      contact and fecal-oral transmission of infectious agents. Widespread use of
      antimicrobial products has prompted concern about emergence of resistance to
      antiseptics and damage to the skin barrier associated with frequent washing. This
      article reviews evidence for the relationship between skin hygiene and infection,
      the effects of washing on skin integrity, and recommendations for skin care
      practices.

PMID- 11294713
TI  - Antiseptic technology: access, affordability, and acceptance.
AB  - Factors other than antimicrobial activity of soaps and antiseptic agents used for
      hand hygiene by health personnel play a role in compliance with recommendations.
      Hand hygiene products differ considerably in acceptance by hospital personnel. If
      switching from a nonmedicated soap to an antiseptic agent or increased use of an
      existing antiseptic agent for hand hygiene prevented a few more infections per
      year, additional expenditures for antiseptic agents would be offset by cost
      savings.

PMID- 11294716
TI  - Preventing nosocomial Mycobacterium tuberculosis transmission in international
      settings.
AB  - Tuberculosis (TB) is a worldwide disease, and nosocomial transmission is known to
      occur. Authoritative preventive guidelines such as the one developed by the
      Centers for Disease Control have been published, but the expenses for
      implementing them can be prohibitive. Each country needs to develop its own
      protocol to prevent nosocomial transmission of TB. This article describes the key
      elements of a protocol undertaken for all public hospitals in Hong Kong, where TB
      is endemic.

PMID- 11294714
TI  - Improving adherence to hand hygiene practice: a multidisciplinary approach.
AB  - Hand hygiene prevents cross-infection in hospitals, but health-care workers'
      adherence to guidelines is poor. Easy, timely access to both hand hygiene and
      skin protection is necessary for satisfactory hand hygiene behavior. Alcohol-
      based hand rubs may be better than traditional handwashing as they require less
      time, act faster, are less irritating, and contribute to sustained improvement in
      compliance associated with decreased infection rates. This article reviews
      barriers to appropriate hand hygiene and risk factors for noncompliance and
      proposes strategies for promoting hand hygiene.

PMID- 11294715
TI  - "Cloud" health-care workers.
AB  - Certain bacteria dispersed by health-care workers can cause hospital infections.
      Asymptomatic health-care workers colonized rectally, vaginally, or on the skin
      with group A streptococci have caused outbreaks of surgical site infection by
      airborne dispersal. Outbreaks have been associated with skin colonization or
      viral upper respiratory tract infection in a phenomenon of airborne dispersal of
      Staphylococcus aureus called the "cloud" phenomenon. This review summarizes the
      data supporting the existence of cloud health-care workers.

PMID- 11294717
TI  - Epidemiology and prevention of pediatric viral respiratory infections in health
      care institutions.
AB  - Nosocomial viral respiratory infections cause considerable illness and death on
      pediatric wards. Common causes of these infections include respiratory syncytial
      virus and influenza. Although primarily a community pathogen, rhinovirus also
      occasionally results in hospitalization and serious sequelae. This article
      reviews effective infection control interventions for these three pathogens, as
      well as ongoing controversies.

PMID- 11294718
TI  - HIV postexposure prophylaxis in the 21st century.
AB  - The administration of postexposure prophylaxis has become the standard of care
      for occupational exposures to HIV. We have learned a great deal about the safety
      and potential efficacy of these agents, as well as the optimal management of
      health-care workers occupationally exposed to HIV. This article describes the
      current state of knowledge in this field, identifies substantive questions to be
      answered, and summarizes basic principles of postexposure management.

PMID- 11294719
TI  - Tuberculosis control in the 21st century.
AB  - In response to tuberculosis (TB) outbreaks in the United States in the late 1980s
      and early 1990s, U.S. hospitals spent tremendous resources to ensure a safer
      workplace. A remarkable decrease in nosocomial transmission resulted, along with
      a decrease in TB cases nationally. Federal standards have been promulgated to
      ensure a safer work environment for all U.S. workers potentially exposed to TB.
      However, these measures may prove costly and burdensome and thus may compromise
      the ability to deliver care.

PMID- 11294720
TI  - Hospital infection control in hematopoietic stem cell transplant recipients.
AB  - Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell
      Transplant Recipients contains a section on hospital infection control including
      evidence-based recommendations regarding ventilation, construction, equipment,
      plants, play areas and toys, health-care workers, visitors, patient skin and oral
      care, catheter-related infections, drug-resistant organisms, and specific
      nosocomial infections. These guidelines are intended to reduce the number and
      severity of hospital infections in hematopoietic stem cell transplant recipients.

PMID- 11294721
TI  - Emerging health care-associated infections in the geriatric population.
AB  - The increasing number of persons >65 years of age form a special population at
      risk for nosocomial and other health care-associated infections. The
      vulnerability of this age group is related to impaired host defenses such as
      diminished cell-mediated immunity. Lifestyle considerations, e.g., travel and
      living arrangements, and residence in nursing homes, can further complicate the
      clinical picture. The magnitude and diversity of health care-associated
      infections in the aging population are generating new arenas for prevention and
      control efforts.

PMID- 11294722
TI  - Emerging waterborne infections in health-care settings.
AB  - Water is used in vast quantities in health-care premises. Many aquatic
      microorganisms can survive and flourish in water with minimal nutrients and can
      be transferred to vulnerable hospital patients in direct (e.g., inhalation,
      ingestion, surface absorption) and indirect ways (e.g., by instruments and
      utensils). Many outbreaks of infection or pseudoinfection occur through lack of
      prevention measures and ignorance of the source and transmission of opportunistic
      pathogens.

PMID- 11294723
TI  - Biofilms and device-associated infections.
AB  - Microorganisms commonly attach to living and nonliving surfaces, including those
      of indwelling medical devices, and form biofilms made up of extracellular
      polymers. In this state, microorganisms are highly resistant to antimicrobial
      treatment and are tenaciously bound to the surface. To better understand and
      control biofilms on indwelling medical devices, researchers should develop
      reliable sampling and measurement techniques, investigate the role of biofilms in
      antimicrobial drug resistance, and establish the link between biofilm
      contamination and patient infection.

PMID- 11294724
TI  - Applying economic principles to health care.
AB  - Applying economic thinking to an understanding of resource use in patient care is
      challenging given the complexities of delivering health care in a hospital.
      Health-care markets lack the characteristics needed to determine a "market" price
      that reflects the economic value of resources used. However, resource allocation
      in a hospital can be analyzed by using production theory to determine efficient
      resource use. The information provided by hospital epidemiologists is critical to
      understanding health-care production processes used by a hospital and developing
      economic incentives to promote antibiotic effectiveness and infection control.

PMID- 11294725
TI  - Economic impact of antimicrobial resistance.
AB  - One reason antimicrobial-drug resistance is of concern is its economic impact on
      physicians, patients, health-care administrators, pharmaceutical producers, and
      the public. Measurement of cost and economic impact of programs to minimize
      antimicrobial-drug resistance is imprecise and incomplete. Studies to describe
      and evaluate the problem will have to employ new methods and be of large scale to
      produce information that is broadly applicable.

PMID- 11294726
TI  - Cost-effective infection control success story: a case presentation.
AB  - In a surgical intensive care unit, the 1996-1997 incidence of central catheter
      associated bloodstream infections exceeded that of hospitals participating in the
      National Nosocomial Infections Surveillance System. Interventions were
      implemented, and a cost-benefit analysis was done that led to hiring a vascular
      catheter care nurse. Subsequent outcome data demonstrated a substantial reduction
      in central catheter-associated bloodstream infections.

PMID- 11294727
TI  - Feeding back surveillance data to prevent hospital-acquired infections.
AB  - We describe the Centers for Disease Control and Prevention's National Nosocomial
      Infections Surveillance system. Elements of the system critical for successful
      reduction of nosocomial infection rates include voluntary participation and
      confidentiality; standard definitions and protocols; identification of
      populations at high risk; site-specific, risk- adjusted infection rates
      comparable across institutions; adequate numbers of trained infection control
      professionals; dissemination of data to health-care providers; and a link between
      monitored rates and prevention efforts.

PMID- 11294728
TI  - Promoting quality through measurement of performance and response: prevention
      success stories.
AB  - Successful efforts to prevent health-care acquired infections occur daily in U.S.
      hospitals. However, few of these "success stories" are presented in the medical
      literature or discussed at professional meetings. Key components of successful
      prevention efforts include multidisciplinary teams, appropriate educational
      interventions, and data dissemination to clinical staff.

PMID- 11294729
TI  - Clinical microbiology in developing countries.
AB  - We review the problem of limited microbiology resources in developing countries.
      We then demonstrate the feasibility of a cohort-based approach to integrate
      microbiology, epidemiology, and clinical medicine to survey emerging infections
      in these countries.

PMID- 11294731
TI  - Molecular approaches to diagnosing and managing infectious diseases: practicality
      and costs.
AB  - As molecular techniques for identifying and detecting microorganisms in the
      clinical microbiology laboratory have become routine, questions about the cost of
      these techniques and their contribution to patient care need to be addressed.
      Molecular diagnosis is most appropriate for infectious agents that are difficult
      to detect, identify, or test for susceptibility in a timely fashion with
      conventional methods.

PMID- 11294730
TI  - New technology for detecting multidrug-resistant pathogens in the clinical
      microbiology laboratory.
AB  - Northwestern Memorial Hospital instituted in-house molecular typing to rapidly
      assess microbial clonality and integrated this typing into an infection control
      program. We compared data on nosocomial infections collected during 24 months
      before and 60 months after implementing the new program. During the intervention
      period, infections per 1,000 patient-days fell 13% (p=0.002) and the percentage
      of hospitalized patients with nosocomial infections decreased 23% (p=0.000006).
      In our hospital, the percentage of patients with nosocomial infections is 43%
      below the U.S. rate. Our typing laboratory costs approximately $400,000 per year,
      a savings of $5.00 for each dollar spent.

PMID- 11294732
TI  - Building communication networks: international network for the study and
      prevention of emerging antimicrobial resistance.
AB  - The global nature of antimicrobial resistance and the failure to control the
      emergence of resistant organisms demand the implementation of a global
      surveillance program involving both developed and developing countries. Because
      of the urgent need for infection control interventions and for rapid distribution
      of information about emerging organisms, we initiated the International Network
      for the Study and Prevention of Emerging Antimicrobial Resistance (INSPEAR). Its
      main objectives are to serve as an early warning system for emerging
      antimicrobial-drug resistant pathogens, to facilitate rapid distribution of
      information about emerging multidrug-resistant pathogens to hospitals and public
      health authorities worldwide, and to serve as a model for the development and
      implementation of infection control interventions.

PMID- 11294733
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus.
AB  - Subtyping methicillin- resistant Staphylococcus aureus (MRSA) isolates and
      tracking nosocomial infections have evolved from phenotypic to genotypic
      approaches; most laboratories now depend on pulsed-field gel electrophoresis
      (PFGE). We discuss the limitations of current image-based genotyping methods,
      including PFGE, and the advantages (including ease of entering data into a
      database) of using DNA sequence analysis to control MRSA infections in health
      care facilities.

PMID- 11294734
TI  - Increasing resistance to vancomycin and other glycopeptides in Staphylococcus
      aureus.
AB  - Strains of Staphylococcus aureus with reduced susceptibility to glycopeptides
      have been reported from Japan, the United States, Europe, and the Far East.
      Although isolates with homogeneous resistance to vancomycin (MICs = 8 microg/mL)
      continue to be rare, there are increasing reports of strains showing
      heteroresistance, often with vancomycin MICs in the 1-4 microg/mL range. Most
      isolates with reduced susceptibility to vancomycin appear to have developed from
      preexisting methicillin-resistant S. aureus infections. Many of the isolates with
      reduced susceptibility to glycopeptides have been associated with therapeutic
      failures with vancomycin. Although nosocomial spread of the vancomycin
      intermediate S. aureus (VISA) strains has not been observed in U.S. hospitals,
      spread of VISA strains has apparently occurred in Japan. Broth microdilution
      tests held a full 24 hours are optimal for detecting resistance in the
      laboratory; however, methods for detecting heteroresistant strains are still in
      flux. Disk-diffusion tests, including the Stokes method, do not detect VISA
      strains. The Centers for Disease Control and Prevention and other groups have
      issued recommendations regarding appropriate infection control procedures for
      patients infected with these strains.

PMID- 11294735
TI  - Controversies about extended-spectrum and AmpC beta-lactamases.
AB  - Many clinical laboratories have problems detecting extended-spectrum beta
      lactamases (ESBLs) and plasmid-mediated AmpC beta-lactamases. Confusion exists
      about the importance of these resistance mechanisms, optimal test methods, and
      appropriate reporting conventions. Failure to detect these enzymes has
      contributed to their uncontrolled spread and sometimes to therapeutic failures.
      Although National Committee for Clinical Laboratory Standards recommendations
      exist for detecting ESBL- producing isolates of Escherichia coli and Klebsiella
      spp., no recommendations exist for detecting ESBLs in other organisms or for
      detecting plasmid-mediated AmpC beta-lactamases in any organisms. Clinical
      laboratories need to have adequate funding, equipment, and expertise to provide a
      rapid and clinically relevant antibiotic testing service in centers where these
      resistance mechanisms are encountered.

PMID- 11294736
TI  - Emerging mechanisms of fluoroquinolone resistance.
AB  - Broad use of fluoroquinolones has been followed by emergence of resistance, which
      has been due mainly to chromosomal mutations in genes encoding the subunits of
      the drugs' target enzymes, DNA gyrase and topoisomerase IV, and in genes that
      affect the expression of diffusion channels in the outer membrane and multidrug
      resistance efflux systems. Resistance emerged first in species in which single
      mutations were sufficient to cause clinically important levels of resistance
      (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). Subsequently, however,
      resistance has emerged in bacteria such as Campylobacter jejuni, Escherichia
      coli, and Neisseria gonorrhoeae, in which multiple mutations are required to
      generate clinically important resistance. In these circumstances, the additional
      epidemiologic factors of drug use in animals and human-to-human spread appear to
      have contributed. Resistance in Streptococcus pneumoniae, which is currently low,
      will require close monitoring as fluoroquinolones are used more extensively for
      treating respiratory tract infections.

PMID- 11294738
TI  - New disinfection and sterilization methods.
AB  - New disinfection methods include a persistent antimicrobial coating that can be
      applied to inanimate and animate objects (Surfacine), a high-level disinfectant
      with reduced exposure time (ortho-phthalaldehyde), and an antimicrobial agent
      that can be applied to animate and inanimate objects (superoxidized water). New
      sterilization methods include a chemical sterilization process for endoscopes
      that integrates cleaning (Endoclens), a rapid (4-hour) readout biological
      indicator for ethylene oxide sterilization (Attest), and a hydrogen peroxide
      plasma sterilizer that has a shorter cycle time and improved efficacy (Sterrad
      50).

PMID- 11294737
TI  - Engineering out the risk for infection with urinary catheters.
AB  - Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial
      infection. Each year, more than 1 million patients in U.S. acute-care hospitals
      and extended-care facilities acquire such an infection; the risk with short-term
      catheterization is 5% per day. CAUTI is the second most common cause of
      nosocomial bloodstream infection, and studies suggest that patients with CAUTI
      have an increased institutional death rate, unrelated to the development of
      urosepsis. Novel urinary catheters impregnated with nitrofurazone or minocycline
      and rifampin or coated with a silver alloy-hydrogel exhibit antiinfective surface
      activity that significantly reduces the risk of CAUTI for short-term
      catheterizations not exceeding 2-3 weeks.

PMID- 11294740
TI  - Can managed health care help manage health care-associated infections?
AB  - Managed-care organizations have a unique opportunity, still largely unrealized,
      to collaborate with health-care providers and epidemiologists to prevent health
      care-associated infections. Several attributes make these organizations logical
      collaborators for infection control programs: they have responsibility for
      defined populations of enrollees and for their overall health, including
      preventive care; they possess unique data resources about their members and their
      care; and they are able to make systemwide changes in care. Health care
      associated infections merit the attention and effort of managed-care
      organizations because these infections are common, incur substantial illness and
      costs, and can be effectively prevented by using methods that are unevenly
      applied in different health-care settings. Both national and local discussions
      will be required to enable the most effective and efficient collaborations
      between managed care organizations and health-care epidemiologists. It will be
      important to articulate clear goals and standards that can be readily understood
      and widely adopted.

PMID- 11294739
TI  - Engineering infection control through facility design.
AB  - Many medical centers have modified their facility design to provide a safer
      environment for patients. From an infection control perspective, the primary
      objective of hospital design is to place the patient at no risk for infection
      while hospitalized. We describe historical landmarks about hospital design,
      modern facility design, and specific designs to prevent acquisition and spread of
      infections such as tuberculosis and aspergillosis.

PMID- 11294741
TI  - Health-care quality promotion through infection prevention: beyond 2000.
AB  - Health-care value purchasing, complex health-care systems, and information
      technology are the three most important change drivers influencing the
      interrelated themes of the 4th decennial conference: accountability, quality
      promotion through infection prevention across the health-care delivery system,
      and medical informatics. Among the change drivers influencing themes of future
      conferences may be a societal mandate for health promotion and health-care access
      for all.

PMID- 11294742
TI  - Rostral ventral medulla 5-HT1A receptors selectively inhibit the
      somatosympathetic reflex.
AB  - The role of the 5-hydroxytryptamine (5-HT1A) receptors in the rostral
      ventrolateral medulla (RVLM) on somatosympathetic, baroreceptor, and
      chemoreceptor reflexes was examined in anesthetized rats. Microinjection of the
      selective 5-HT1A agonist 8-hydroxy-di-n-propylamino tetralin (8-OH-DPAT)
      decreased arterial blood pressure and splanchnic sympathetic nerve activity
      (SNA). Electrical stimulation of the hindlimb evoked early and late excitatory
      sympathetic responses. Bilateral microinjection in the RVLM of 8-OH-DPAT markedly
      attenuated both the early and late responses. This potent inhibition of the
      somatosympathetic reflex persisted even after SNA and arterial blood pressure
      returned to preinjection levels. Preinjection of the selective 5-HT1A antagonist
      NAN-190 in the RVLM blocked the sympathoinhibitory effect of 8-OH-DPAT and
      attenuated the inhibitory effect on the somatosympathetic reflex. 8-OH-DPAT
      injected in the RVLM did not affect baroreceptor or chemoreceptor reflexes. Our
      findings suggest that activation of 5-HT1A receptors in the RVLM exerts a potent,
      selective inhibition on the somatosympathetic reflex.

PMID- 11294743
TI  - Expression of endothelial nitric oxide synthase in the postnatal developing
      porcine kidney.
AB  - The postnatal pattern of renal endothelial nitric oxide synthase (eNOS) is
      unknown. The purpose of this study was to characterize eNOS expression during
      maturation and compare this to neuronal NOS (nNOS). The experiments measured
      whole kidney eNOS mRNA expression by RT-PCR and protein content by Western blot,
      as well as cortical and medullary protein content in piglets at selected
      postnatal ages and in adult pigs. Whole kidney eNOS mRNA was compared with nNOS.
      Whole kidney eNOS expression decreased from the newborn to its lowest at 7 days,
      returning by 14 days to adult levels. This eNOS mRNA pattern contrasted with
      nNOS, which was highest at birth, and progressively decreased to its lowest level
      in the adult. At birth, cortical eNOS protein was greater than medullary,
      contrasting with the adult pattern of equivalent levels. In conclusion eNOS is
      developmentally regulated during early renal maturation and may critically
      participate in renal function during this period. The eNOS developmental pattern
      differs from nNOS, suggesting that these isoforms may have different regulatory
      factors and functional contributions in the postnatal kidney.

PMID- 11294744
TI  - Injection of muscimol in dorsomedial hypothalamus and stress-induced Fos
      expression in paraventricular nucleus.
AB  - Prior microinjection of the GABA(A)-receptor agonist muscimol into the
      dorsomedial hypothalamus (DMH) in conscious rats attenuates the increases in
      heart rate, blood pressure, and circulating adrenocorticotrophic hormone seen in
      air stress. Here, we examined the effect of similar treatment on air stress- or
      hemorrhage-induced Fos expression in the paraventricular nucleus (PVN). Muscimol
      (80 pmol/100 nl per side) or saline (100 nl per side) was microinjected
      bilaterally into the DMH in conscious rats before either air stress, an emotional
      or neurogenic stressor, or graded hemorrhage, a physiological stressor. Each
      stressor evoked a characteristic pattern of Fos expression in the parvocellular
      and magnocellular PVN after saline. Injection of muscimol into the DMH suppressed
      Fos expression in the PVN associated with air stress but not with hemorrhage.
      Injection of muscimol at sites anterior to the DMH and closer to the PVN had no
      effect on Fos expression in the PVN after air stress. Thus activation of neurons
      in the DMH is necessary for excitation of neurons in the PVN during air stress
      but not during hemorrhage.

PMID- 11294745
TI  - Glutamate release via NO production evoked by NMDA in the NTS enhances
      hypotension and bradycardia in vivo.
AB  - Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role
      in regulating sympathetic nerve activity. The aims of this study were to
      determine whether the activation of N-methyl-D-aspartate (NMDA) receptors in the
      NTS facilitates the release of L-glutamate (Glu) via NO production, and, if so,
      to determine whether this mechanism is involved in the depressor and bradycardic
      responses evoked by NMDA. We measured the production of NO in the NTS as NO2- and
      NO3- (NO(x)) or Glu levels by in vivo microdialysis before, during, and after
      infusion of NMDA in anesthetized rats. We also examined effects of N(omega)-nitro
      L-arginine methyl ester (L-NAME) on the changes in these levels. NMDA elicited
      depressor and bradycardic responses and increased the levels of NO(x) and Glu. L
      NAME abolished the increases in the levels of NO(x) and Glu and attenuated
      cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor
      activation in the NTS induces Glu release through NO synthesis and that Glu
      released via NO enhances depressor and bradycardic responses.

PMID- 11294747
TI  - Interaction of serotonin and cholecystokinin in the lateral parabrachial nucleus
      to control sodium intake.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] and CCK injected into the lateral
      parabrachial nucleus (LPBN) inhibit NaCl and water intake. In this study, we
      investigated interactions between 5-HT and CCK into the LPBN to control water and
      NaCl intake. Male Holtzman rats with cannulas implanted bilaterally in the LPBN
      were treated with furosemide + captopril to induce water and NaCl intake.
      Bilateral LPBN injections of high doses of the 5-HT antagonist methysergide (4
      microg) or the CCK antagonist proglumide (50 microg), alone or combined, produced
      similar increases in water and 1.8% NaCl intake. Low doses of methysergide (0.5
      microg) + proglumide (20 microg) produced greater increases in NaCl intake than
      when they were injected alone. The 5-HT(2a/2c) agonist 2,5-dimetoxy-4
      iodoamphetamine hydrobromide (DOI; 5 microg) into the LPBN reduced water and NaCl
      intake. After proglumide (50 microg) + DOI treatment, the intake was not
      different from vehicle treatment. CCK-8 (1 microg) alone produced no effect. CCK
      8 combined with methysergide (4 microg) reduced the effect of methysergide on
      NaCl intake. The data suggest that functional interactions between 5-HT and CCK
      in the LPBN may be important for exerting inhibitory control of NaCl intake.

PMID- 11294746
TI  - Acute exercise induced changes in rat skeletal muscle mRNAs and proteins
      regulating type IV collagen content.
AB  - This experiment tested the hypothesis that running-induced damage to rat skeletal
      muscle causes changes in synthesis and degradation of basement membrane type IV
      collagen and to proteins regulating its degradation. Samples from soleus muscle
      and red and white parts of quadriceps femoris muscle (MQF) were collected 6 h or
      1, 2, 4, or 7 days after downhill running. Increased muscle beta-glucuronidase
      activity indicated greater muscle damage in the red part of MQF than in the white
      part of MQF or soleus. In the red part of MQF, type IV collagen expression was
      upregulated at the pretranslational level and the protein concentration
      decreased, whereas matrix metalloproteinase-2 (MMP-2), a protein that degrades
      type IV collagen, and tissue inhibitor of metalloproteinase-2 (TIMP-2), a protein
      that inhibits degradation, were increased in parallel both at mRNA and protein
      levels. Type IV collagen mRNA level increased in the white part of MQF and soleus
      muscle. The protein concentration increased in the white part of MQF and was
      unchanged in soleus muscle. MMP-2 and TIMP-2 changed only slightly in the white
      part of MQF and soleus muscle. The changes seem to depend on the severity of
      myofiber injury and thus probably reflect reorganization of basement membrane
      compounds.

PMID- 11294749
TI  - Meal-related stimuli differentially induce c-Fos activation in the nucleus of the
      solitary tract.
AB  - Feedback signals arising from the oral cavity and upper gastrointestinal tract
      contribute to the control of meal size. To assess how these signals are
      integrated at central sites involved in ingestive control, we compared levels of
      c-Fos activation in the nucleus of the solitary tract (NTS) and area postrema
      (AP) in response to meal ingestion or gastric and duodenal infusions in the rat.
      Ingestion of a liquid diet to satiety induced significant fos-like
      immunoreactivity (FLI) at multiple levels of the NTS and within the AP. The
      restriction of intake to one-half the normal ingestion of a rat did not result in
      significant FLI, although gastric infusion of this liquid diet volume did. Fast
      bolus infusion resulted in greater FLI than did the same volume infused at a rate
      to mimic that of normal ingestion. Prior experience with gastric infusions did
      not affect the amounts of FLI within the NTS or AP. In rats with pyloric cuffs
      blocking flow from the stomach to the intestine, combined gastric load and
      duodenal nutrient elicited significantly greater FLI than either gastric or
      duodenal infusions alone. These data demonstrate that neural activation arising
      from meal-related stimuli are integrated at the level of the NTS.

PMID- 11294748
TI  - Sites and ionic mechanisms of hypoxic vasoconstriction in frog skin.
AB  - We tested the hypothesis that the cellular mechanisms mediating hypoxic
      vasoconstriction (HVC) in frog skin, an important vertebrate respiratory organ,
      are similar to those mediating HVC in the pulmonary vasculature of mammals. An
      accepted hypothesis in the lung is that alveolar hypoxia alters the redox
      potential in vascular smooth muscle cells of arterial vessels. This decreases
      membrane K+ conductance, causing depolarization. Depolarization increases the
      open probability of L-type Ca2+ channels, facilitating Ca2+ entry into the cell,
      which leads to vascular smooth muscle contraction and vasoconstriction. We
      studied the cutaneous microcirculation of the frog (Xenopus laevis) web by
      enclosing the web in a transparent chamber that was ventilated with different gas
      mixtures. Arteriolar and venular diameters were measured by video microscopy.
      Drugs were applied topically or intravascularly. A dose-dependent constriction to
      hypoxia occurred in arterioles but not venules, although both vessel types
      constricted to similar degrees to the thromboxane mimetic U-46619. The magnitude
      of HVC was not associated with arteriolar size. Constriction of arterioles with 4
      amino pyridine, a K+-channel antagonist, was blocked by the L-type Ca2+-channel
      blocker nifedipine. Nifedipine also antagonized HVC and hypercapnic
      vasoconstriction. Bay K 8664, a drug that increases the open probability of L
      type Ca2+ channels, augmented HVC. These data support our hypothesis that the
      cellular mechanisms mediating HVC are similar in frog skin and mammalian lungs.
      This similarity between amphibian and mammalian tissues suggests that the
      mechanisms of HVC may have arisen relatively early in vertebrate evolution. In
      addition, because of its structural simplicity and easy accessibility, frog skin
      may be a useful tissue for studying this general phenomenon in vivo.

PMID- 11294750
TI  - Hemodynamic, renal, and endocrine responses to acute ET(A) blockade at different
      ANG II plasma levels.
AB  - Angiotensin (ANG) II effects may be partly mediated by endothelin (ET)-1. This
      study analyses the hemodynamic, renal, and hormonal responses of acute ET(A)
      receptor antagonism (LU-135252) at two ANG II plasma levels in eight conscious
      dogs. Protocol 1 involved a 60-min baseline, followed by two doses of ANG II for
      60 min each (4 and 20 ng. kg(-1). min(-1)), termed ANG II 4 (slightly increased)
      and ANG II 20 (pathophysiologically increased ANG II plasma concentration).
      Protocol 2 was the same as protocol 1 but included 15 mg/kg iv LU-135252 after
      the baseline period. Protocol 3 was a 3-h time control. ANG II without LU-135252
      did not increase plasma big ET-1 and ET-1, whereas LU-135252 increased ET-1
      transiently after injection. This transient ET-1 increase was not reflected in
      urinary ET-1 excretion. The ANG II induced decreases in sodium, water, and
      potassium excretion, glomerular filtration rate, and fractional sodium excretion
      were not different with and without LU-135252. Mean arterial pressure increased
      during ANG II and was not lower with LU-135252 (-6 mmHg, not significant). Most
      importantly, during ANG II 20 LU-135252 prevented the decrease in cardiac output.
      Simultaneously, systemic vascular resistance increased 40% less, pulmonary
      vascular resistance was maintained at baseline levels, and central venous and
      wedge pressure were lower. Because ANG II stimulated endothelin de novo synthesis
      should just have started after 2 h of ANG II infusion, there must be mechanisms
      other than blocking the coupling of de novo synthesized endothelins to the ET(A)
      receptors to explain the effects of acute ET(A) receptor inhibition in our
      setting.

PMID- 11294751
TI  - Troglitazone stimulates pancreatic growth in congenitally CCK-A receptor
      deficient OLETF rats.
AB  - We examined the effect of troglitazone treatment on pancreatic growth in the CCK
      A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal
      model for type 2 diabetes mellitus. A troglitazone-rich diet (0.2%) was given
      from 12 to 28 wk of age or from 12 or 28 wk of age to 72 wk of age. Fasting serum
      glucose concentrations in control OLETF rats increased progressively with age,
      which was almost completely prevented by troglitazone treatment. Insulin levels
      in serum and pancreatic content in the control rat markedly increased at 28 wk of
      age but significantly decreased at 72 wk of age compared with those at 12 wk of
      age, whereas those in troglitazone-treated rats were nearly the same at all ages
      and were similar to those in control rats at 12 wk of age. Pancreatic wet weight
      in control rats decreased with age irrespective of whether they were
      hyperinsulinemic (28 wk old) or hypoinsulinemic (72 wk old). Troglitazone
      treatment significantly increased pancreatic wet weight and protein, DNA, and
      enzyme contents compared with those in the control rats. Moreover, troglitazone
      treatment completely prevented or reversed histological alterations such as
      fibrosis, fatty replacement, and inflammatory cell infiltration. Our results
      indicate that troglitazone stimulates pancreatic growth in the congenitally CCK-A
      receptor-deficient OLETF rat not only by reducing insulin resistance and
      potentiating insulin action but also by suppressing inflammatory changes in the
      pancreas.

PMID- 11294752
TI  - Effects of estrogen on thermoregulatory tail vasomotion and heat-escape behavior
      in freely moving female rats.
AB  - Effects of estrogen on thermoregulatory vasomotion and heat-escape behavior were
      investigated in ovariectomized female rats supplemented with estrogen (replaced
      estrogen rats) or control saline (low estrogen rats). First, we measured tail
      temperature of freely moving rats at ambient temperatures (T(a)) between 13 and
      31 degrees C. Tail temperature of the low estrogen rats was higher than that of
      the replaced estrogen rats at T(a) between 19 and 25 degrees C, indicating that
      the low estrogen rats exhibit more skin vasodilation than the replaced estrogen
      rats. There was no significant difference in oxygen consumption and core
      temperature between the two groups. Second, we analyzed heat-escape behaviors in
      a hot chamber where rats could obtain cold air by moving in and out of a reward
      area. The low estrogen rats kept T(a) at a lower level than did the replaced
      estrogen rats. These results imply that the lack of estrogen facilitates heat
      dissipation both by skin vasodilation and by heat-escape behavior. Ovariectomized
      rats may mimic climacteric hot flushes not only for autonomic skin vasomotor
      activity but also for thermoregulatory behavior.

PMID- 11294754
TI  - Differential expression of uterine NO in pregnant and nonpregnant rats with
      intrauterine bacterial infection.
AB  - Previous studies have demonstrated that nitric oxide (NO) is involved in the
      uterine host defense against bacterial infection. In nonpregnant rats, NO
      production in the uterus was shown to be lower, and inducible NO synthase (NOS)
      expression was undetectable. However, studies in pregnant rats show abundant
      expression of inducible NOS with significant elevation in NO production in the
      uterus. We have recently reported that intrauterine Escherichia coli infection
      caused a localized increase in uterine NO production and inducible NOS expression
      in the nonpregnant rat. In our present study, we examined whether the uterine NO
      production, NOS expression, and uterine tumor necrosis factor-alpha protein are
      increased in pregnant rats with intrauterine pathogenic Escherichia coli
      infection. Unlike the nonpregnant state, the NO production in the infected
      uterine horn of pregnant rats was not significantly elevated after bacterial
      inoculation compared with the contralateral uterine horn. The expression of
      uterine NOS (types II and III) also did not show significant upregulation in the
      infected horn. This is in contrast to that in nonpregnant animals, in which type
      II NOS was induced in the uterus on infection. Moreover, intrauterine infection
      induced an elevated expression of tumor necrosis factor-alpha protein in the
      infected horn both of nonpregnant and of pregnant rats. These data suggest that
      the sequential stimulation of NOS expression, especially the inducible isoform,
      and generation of uterine NO are lacking during pregnancy despite an elevated
      tumor necrosis factor-alpha after infection. In summary, NO synthesis response
      may be maximal at pregnancy, and infection may not further induce the NO system.
      Present studies, together with our previous report that intrauterine infection
      induced lethality in pregnancy rats was amplified with the inhibition of NO,
      suggest that pregnancy is a state predisposed for increased complications
      associated with intrauterine infection and that the constitutively elevated
      uterine NO during pregnancy may help contain or even reduce the risk of infection
      related complications.

PMID- 11294753
TI  - Rhythmicity of the cGMP-related signal transduction pathway in the mammalian
      circadian system.
AB  - Entrainment of mammalian circadian rhythms requires the activation of specific
      signal transduction pathways in the suprachiasmatic nuclei (SCN). Pharmacological
      inhibition of kinases such as cGMP-dependent kinase (PKG) or Ca2+/calmodulin
      dependent kinase, but not cAMP-dependent kinase, blocks the circadian responses
      to light in vivo. Here we show a diurnal and circadian rhythm of cGMP levels and
      PKG activity in the hamster SCN, with maximal values during the day or subjective
      day. This rhythm depends on phosphodiesterase but not on guanylyl cyclase
      activity. Five-minute light pulses increased cGMP levels at the end of the
      subjective night [circadian time 18 (CT18)], but not at CT13.5. Western blot
      analysis indicated that the PKG II isoform is the one present in the SCN.
      Inhibition of PKG or guanylyl cyclase in vivo significantly attenuated light
      induced phase shifts at CT18 (after 5-min light pulses) but did not affect c-Fos
      expression in the SCN. These results suggest that cGMP and PKG are related to SCN
      responses to light and undergo diurnal and circadian changes.

PMID- 11294755
TI  - Effect of suprachiasmatic nucleus lesion on circadian dentin increment in rats.
AB  - Mammalian dentin universally shows circadian increments. However, little is known
      about the mechanism of this phenomenon. The purpose of the present study was to
      investigate the role of the suprachiasmatic nucleus (SCN) in the generation of
      circadian rhythm in dentin increment. Rats underwent lesion of the SCN by
      electrodes and were maintained under constant light to examine whether the
      circadian increment free runs. The rats were injected with nitrilotriacetato lead
      to chronologically label the growing dentin. Two weeks after the operation,
      maxillary incisors and the locations of lesions in the brain were examined
      histologically. A harmonic (Fourier) analysis was performed to examine the
      densitometric pattern of the dentin increments to determine their periodicity. In
      rats with a completely lesioned SCN, ultradian increments, but no circadian
      increments, were observed in the dentin. Alternatively, in rats with an intact or
      only partially lesioned SCN, circadian increments persisted or were only
      temporarily disturbed. These results suggest that the SCN plays an important role
      in the generation of the circadian dentin increment in rats.

PMID- 11294756
TI  - Vagal and spinal mechanosensors in the rat stomach and colon have multiple
      receptive fields.
AB  - Mechano- and chemosensitive extrinsic primary afferents innervating the
      gastrointestinal tract convey important information regarding the state of
      ingested nutrients and specific motor patterns to the central nervous system via
      splanchnic and vagal nerves. Little is known about the organization of peripheral
      receptive sites of afferents and their correspondence to morphologically
      identified terminal structures. Mechano- and chemosensory characteristics and
      receptive fields of single vagal fibers innervating the stomach as well as lumbar
      splanchnic nerves innervating the distal colon were identified using an in vitro
      perifusion system. Twenty-three (17%) of one-hundred thirty-six vagal units
      identified were found to have multiple, punctate receptive fields, up to 35 mm
      apart, and were distributed throughout the stomach. Evidence was based on
      similarity of generated spike forms, occlusion, and latency determinations. Most
      responded with brief bursts of activity to mucosal stroking with von Frey hairs
      (10-200 mg) but not to stretch, and 32% responded to capsaicin (10(-5) M). They
      were classified as rapidly adapting mucosal receptors. Four (8%) of fifty-three
      single units recorded from the lumbar splanchnic nerve had more than one,
      punctate receptive field in the distal colon, up to 40 mm apart. They responded
      to blunt probing, particularly from the serosal side, and variously to chemical
      stimulation with 5-hydroxytryptamine and capsaicin. We conclude that a proportion
      of gastrointestinal mechanosensors has multiple receptive fields and suggest that
      they integrate mechanical and chemical information from an entire organ,
      constituting the generalists in visceral sensation.

PMID- 11294757
TI  - Intestinal satiety protein apolipoprotein AIV is synthesized and regulated in rat
      hypothalamus.
AB  - Apolipoprotein AIV (apo AIV) is a satiety protein secreted by the small
      intestine. We demonstrate for the first time that apo AIV protein and apo AIV
      mRNA are present in rat hypothalamus, a site intimately involved in the
      integration of signals for regulation of food intake and energy metabolism. We
      further characterized the regulation of hypothalamic apo AIV mRNA levels. Food
      deprived animals showed a pronounced decrease in gene expression of apo AIV in
      the hypothalamus, with a concomitant decrease in the jejunum. Refeeding fasted
      rats with standard laboratory chow for 4 h evokes a significant increase of apo
      AIV mRNA in jejunum but not in hypothalamus. However, lipid refeeding to the
      fasted animals restored apo AIV mRNA levels both in hypothalamus and jejunum.
      Intracerebroventricular administration of apo AIV antiserum not only stimulated
      feeding, but also decreased apo AIV mRNA level in the hypothalamus. These data
      further confirm the central role of apo AIV in the regulation of food intake.

PMID- 11294758
TI  - Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II
      hypertension.
AB  - The purpose of this study was to determine the role of endothelin in mediating
      the renal hemodynamic and arterial pressure changes observed during chronic ANG
      II-induced hypertension. ANG II (50 ng x kg(-1) x min(-1)) was chronically
      infused into the jugular vein by miniosmotic pump for 2 wk in male Sprague-Dawley
      rats with and without endothelin type A (ET(A))-receptor antagonist ABT-627 (5 mg
      x kg(-1) x day(-1)) pretreatment. Arterial pressure increased in ANG II rats
      compared with control rats (149 +/- 5 vs. 121 +/- 6 mmHg, P < 0.05,
      respectively). Renal expression of preproendothelin mRNA was increased by
      approximately 50% in both the medulla and cortex of ANG II rats. The hypertensive
      effect of ANG II was completely abolished in rats pretreated with the ET(A)
      receptor antagonist (114 +/- 5 mmHg, P < 0.05). Glomerular filtration rate was
      decreased by 33% in ANG II rats, and this response was attenuated in rats
      pretreated with ET(A)-receptor antagonist. These data indicate that activation of
      the renal endothelin system by ANG II may play an important role in mediating
      chronic renal and hypertensive actions of ANG II.

PMID- 11294759
TI  - Suppression and recovery of estrous behavior in Syrian hamsters after changes in
      metabolic fuel availability.
AB  - A reduction in the availability of oxidizable metabolic fuels inhibits
      reproduction. Forty-eight hours of metabolic fuel deprivation inhibits estrous
      behavior in ovariectomized, steroid-treated Syrian hamsters, but little is known
      about the time course of this inhibition. Likewise, refeeding reverses
      deprivation-induced suppression, but the rate of recovery has not been examined.
      In two experiments we determined 1) the rate at which estrous behavior declines
      in hamsters treated with metabolic inhibitors and 2) how rapidly sexual
      receptivity is restored when hamsters are refed after a 48-h fast. We also
      measured circulating levels of leptin and insulin in an attempt to determine
      their relationship to the inhibition and restoration of estrous behavior. More
      than 24 h of metabolic inhibitor administration were required to inhibit
      lordosis, whereas only 6 h of refeeding were sufficient to restore the display of
      sexual receptivity to normal levels. Neither plasma insulin nor leptin levels
      paralleled the changes in estrous behavior. We concluded that 1) suppression of
      estrous behavior occurs more slowly than recovery after a fast and 2) changes in
      circulating leptin and insulin probably do not have a critical role in these
      behavioral changes.

PMID- 11294760
TI  - A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin
      in cardiomyocytes.
AB  - We previously reported that cardiomyocytes produce endothelin (ET)-1 and that the
      tissue level of ET-1 markedly increased in failing hearts in rats with chronic
      heart failure. Because the level of plasma ET-1 also increased progressively in
      patients with breast cancer who received doxorubicin (Dox; Adriamycin), which
      possesses cardiotoxicity, we hypothesized that ET-1 plays a role in the
      pathophysiology of cardiomyocytes injured by Dox. In this study, we investigated
      the effect of ET-1 on the cytotoxicity of Dox in primary cultured neonatal rat
      cardiomyocytes. The results showed that ET-1 effectively attenuated Dox-induced
      acute cardiomyocyte cytotoxicity (24-h incubation with Dox) evaluated by in vitro
      cell toxicity assay [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium
      bromide (MTT) assay and lactate dehydrogenase release]. The cytoprotective effect
      of ET-1 was mediated via ET(A) receptors, because pretreatment with the ET(A)
      receptor antagonist BQ123 completely suppressed the cytoprotective effect of ET
      1, whereas the ET(B)-receptor antagonist BQ788 did not. The cytoprotective effect
      of ET-1 was abolished by pretreatment with cycloheximide or staurosporine. These
      results suggest that a protein molecule(s), which is synthesized de novo by the
      stimulation of protein kinase pathway, is involved in the cytoprotective effect
      of ET-1. ET-1 increased the expression of an endogenous antioxidant, manganese
      superoxide dismutase (Mn-SOD), in the cardiomyocytes, as demonstrated by a
      Western blotting analysis. Pretreatment with an antisense
      oligodeoxyribonucleotide of Mn-SOD markedly attenuated the cytoprotective effect
      of ET-1 on the Dox-induced cytotoxicity. However, under conditions of prolonged
      incubation with Dox (48 h), ET-1 did not affect Dox-induced cardiomyocyte
      cytotoxicity in culture. These results suggest that ET-1 prevents the early phase
      of Dox-induced cytotoxicity via the upregulation of the antioxidant Mn-SOD
      through ET(A) receptors in cultured cardiomyocytes.

PMID- 11294761
TI  - Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition
      reflex pathway in the rat.
AB  - 5-Hydroxytryptamine (5-HT) receptors in the central nervous system have been
      implicated in the control of micturition. The present study was undertaken to
      evaluate the effects of a selective 5-HT1A-receptor antagonist [N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide
      trihydrochloride (WAY100635)] on the micturition-reflex pathway in urethane
      anesthetized female Wistar rats. Rhythmic isovolumetric bladder contractions
      evoked by bladder distension were abolished by 0.3- to 3-mg/kg iv or 30- to 100
      microg intrathecal (it) administration of WAY100635 in a dose-dependent manner
      for periods of 3-15 min. Intrathecal injection of WAY100635 was effective only if
      injected at the L6-S1 spinal cord level, but not at the thoracic or cervical cord
      levels. WAY100635 (30-100 microg it) significantly reduced the amplitude of
      bladder contractions evoked by electrical stimulation of the pontine micturition
      center. However, the field potentials in the rostral pons evoked by electrical
      stimulation of pelvic nerve were not affected by intrathecal or intravenous
      injection of WAY100635. These results suggest that 5-HT1A receptors at the L6-S1
      level of the spinal cord have an important role in the tonic control of the
      descending limb of the micturition-reflex pathway in the rat.

PMID- 11294762
TI  - Role of spinal alpha1-adrenoceptor subtypes in the bladder reflex in anesthetized
      rats.
AB  - The contribution of different subtypes of alpha1-adrenoceptors in the lumbosacral
      spinal cord to the control of the urinary bladder was examined in urethane
      anesthetized rats. Bladder pressure was recorded via a transurethral catheter
      under isovolumetric conditions. Drugs were administered intrathecally at the L6
      S1 segmental level of spinal cord. RS-100329 (an alpha1A-antagonist) in doses of
      25, 50, and 100 nmol significantly decreased bladder-contraction amplitude by
      38%, 52%, and 95%, respectively, whereas (+)-cyclazosin (an alpha1B-antagonist)
      significantly decreased bladder-contraction amplitude (48% reduction) only in a
      50-nmol but not a 100-nmol dose. Fifty nanomoles of RS-100329 and (+)-cyclazosin
      increased bladder-contraction frequency by 54% and 44%, respectively. BMY7378 (an
      alpha1D-antagonist), in doses of 25, 50, and 100 nmol, did not change bladder
      activity. These studies suggest that reflex-bladder activity is modulated by two
      types of spinal alpha1-adrenergic mechanisms: 1) alpha1A- or alpha1B-inhibitory
      control of the frequency of voiding reflexes presumably mediated by an alteration
      in the processing of bladder afferent input and 2) alpha(1A)-facilitatory
      modulation of the descending efferent limb of the micturition-reflex pathway.
      Spinal alpha1D-adrenoceptors do not appear to have a significant role at either
      site.

PMID- 11294763
TI  - L-364,718, a cholecystokinin-A receptor antagonist, suppresses feeding-induced
      sleep in rats.
AB  - Feeding induces increased sleep in several species, including rats. The aim of
      the study was to determine if CCK plays a role in sleep responses to feeding. We
      induced excess eating in rats by 4 days of starvation and studied the sleep
      responses to refeeding in control and CCK-A receptor antagonist-treated animals.
      Sleep was recorded on 2 baseline days when food was provided ad libitum. After
      the starvation period, sleep was recorded on 2 refeeding days when the control
      rats (n = 8) were injected with vehicle and the experimental animals (n = 8)
      received intraperitoneal injections of L-364,718 (500 microg/kg, on both
      refeeding days). In the control group, refeeding caused increases in rapid eye
      movement sleep (REMS) and non-REMS (NREMS) and decreases in NREMS intensity as
      indicated by the slow-wave activity (SWA) of the electroencephalogram. CCK-A
      receptor antagonist treatment completely prevented the SWA responses and delayed
      the NREMS responses to refeeding; REMS responses were not simply abolished, but
      the amount of REMS was below baseline after the antagonist treatment. These
      results suggest that endogenous CCK, acting on CCK-A receptors, may play a key
      role in eliciting postprandial sleep.

PMID- 11294764
TI  - Low levels of K(ATP) channel activation decrease excitability and contractility
      of urinary bladder.
AB  - Activation of ATP-sensitive potassium (K(ATP)) channels can regulate smooth
      muscle function through membrane potential hyperpolarization. A critical issue in
      understanding the role of K(ATP) channels is the relationship between channel
      activation and the effect on tissue function. Here, we explored this relationship
      in urinary bladder smooth muscle (UBSM) from the detrusor by activating K(ATP)
      channels with the synthetic compounds N-(4-benzoylphenyl)-3,3,3-trifluoro-2
      hydroxy-2-methylpropionamide (ZD-6169) and levcromakalim. The effects of ZD-6169
      and levcromakalim on K(ATP) channel currents in isolated UBSM cells, on action
      potentials, and on related phasic contractions of isolated UBSM strips were
      examined. ZD-6169 and levcromakalim at 1.02 and 2.63 microM, respectively, caused
      half-maximal activation (K1/2) of K(ATP) currents in single UBSM cells (see
      Heppner TJ, Bonev A, Li JH, Kau ST, and Nelson MT. Pharmacology 53: 170-179,
      1996). In contrast, much lower concentrations (K(1/2) = 47 nM for ZD-6169 and
      K1/2 = 38 nM for levcromakalim) caused inhibition of action potentials and phasic
      contractions of UBSM. The results suggest that activation of <1% of K(ATP)
      channels is sufficient to inhibit significantly action potentials and the related
      phasic contractions.

PMID- 11294765
TI  - Staphylococcal enterotoxin B induces fever, brain c-Fos expression, and serum
      corticosterone in rats.
AB  - The paraventricular nucleus of the hypothalamus (PVH) occupies a pivotal point
      within the network of brain nuclei coordinating critical host-defense responses.
      In mice, T cell-dependent immune stimuli, including the bacterial superantigen
      staphylococcal enterotoxin B (SEB), can activate the PVH. To determine whether T
      cell-dependent immune stimuli activate the PVH in rats, we assessed plasma
      corticosterone (Cort) levels, fever responses, and c-Fos expression in the PVH in
      animals treated with intraperitoneal injections of SEB. In animals with
      previously implanted abdominal thermisters, intraperitoneal injection of 1 mg/kg
      SEB resulted in a significant rise in body temperature, with a latency of 3.5-4
      h. In separate animals, intraperitoneal injection of 1 mg/kg SEB resulted in a
      significant elevation of plasma Cort and induced c-Fos expression in
      parvocellular neurons within the PVH. These results support the idea that T cell
      dependent immune stimuli activate brain pathways mediating host-defense responses
      such as fever and neuroendocrine changes.

PMID- 11294766
TI  - Glucocorticoids modulate baroreflex control of renal sympathetic nerve activity.
AB  - Experiments were performed to determine the effects of glucocorticoids on
      arterial baroreceptor reflex control of renal sympathetic nerve activity (RSNA).
      Intravenous infusions of phenylephrine and nitroprusside were used to produce
      graded changes in arterial pressure (AP) in Inactin-anesthetized male Sprague
      Dawley rats. Baroreflex control of RSNA was determined during a baseline period
      and 2 and 3 h after administration of the glucocorticoid type II receptor
      antagonist Mifepristone (30 mg/kg sc) or vehicle (oil). Corticosterone (cort)
      treatment (100 mg cort pellet sc for 2-3 wk) increased baseline AP from 115 +/- 2
      to 128 +/- 1 mmHg. Cort treatment also decreased the gain coefficient and
      increased the midpoint of the baroreflex curve. Treatment of cort rats with
      Mifepristone decreased AP within 2 h and increased the gain coefficient and
      decreased the midpoint of the baroreflex function curve back toward values
      measured in control rats. Mifepristone altered the baroreflex function curve even
      when AP was maintained at baseline levels. Therefore, these data demonstrate for
      the first time that glucocorticoids can modulate baroreflex control of RSNA by a
      mechanism that is, in part, independent of changes in AP.

PMID- 11294767
TI  - Activation of histamine H3 receptors inhibits renal noradrenergic
      neurotransmission in anesthetized dogs.
AB  - To investigate the possible involvement of histamine H(3) receptors in renal
      noradrenergic neurotransmission, effects of (R)alpha-methylhistamine (R-HA), a
      selective H3-receptor agonist, and thioperamide (Thiop), a selective H3-receptor
      antagonist, on renal nerve stimulation (RNS)-induced changes in renal function
      and norepinephrine (NE) overflow in anesthetized dogs were examined. RNS (0.5-2.0
      Hz) produced significant decreases in urine flow and urinary sodium excretion and
      increases in NE overflow rate (NEOR), without affecting renal hemodynamics. When
      R-HA (1 microg x kg(-1) x min(-1)) was infused intravenously, mean arterial
      pressure and heart rate were significantly decreased, and there was a tendency to
      reduce basal values of urine flow and urinary sodium excretion. During R-HA
      infusion, RNS-induced antidiuretic action and increases in NEOR were markedly
      attenuated. Thiop infusion (5 microg x kg(-1) x min(-1)) did not affect basal
      hemodynamic and excretory parameters. Thiop infusion caused RNS-induced
      antidiuretic action and increases in NEOR similar to the basal condition. When R
      HA was administered concomitantly with Thiop infusion, R-HA failed to attenuate
      the RNS-induced antidiuretic action and increases in NEOR. However, in the
      presence of pyrilamine (a selective H1-receptor antagonist) or cimetidine (a
      selective H2-receptor antagonist) infusion, R-HA attenuated the RNS-induced
      actions, similarly to the case without these antagonists. Thus functional
      histamine H3 receptors, possibly located on renal noradrenergic nerve endings,
      may play the role of inhibitory modulators of renal noradrenergic
      neurotransmission.

PMID- 11294768
TI  - Fever and behavioral thermoregulation in young and old rats.
AB  - At standard laboratory ambient temperatures (T(a)) of 20-24 degrees C, peripheral
      injections of lipopolysaccharide (LPS) reliably produce fever in young rats. In
      contrast, old rats may show a blunted fever, no fever, or even hypothermia after
      LPS. In the present study we hypothesized that old rats might use behavioral
      thermoregulation to help them develop a fever. Young and old rats were implanted
      with temperature transmitters. At least 1 wk postoperatively they were placed in
      a thermally graded alleyway (T(a) 10-40 degrees C). On the third and sixth day
      they were taken out of the gradient, placed at an T(a) of 23 degrees C, injected
      intraperitoneally with LPS or saline, and left at 23 degrees C for 3 h. At the
      end of that time, all young rats had become febrile, whereas the old rats had
      not. When the rats were replaced in the thermal gradient, the young animals
      continued to develop a fever that was similar to fever in young rats left at 23
      degrees C. The old animals chose significantly warmer positions in the thermal
      gradient than did the young animals and only then became febrile. Although there
      was a tendency for the young rats to prefer higher T(a) after LPS than after
      saline, these differences were not significant. However, the differences in the
      old rats were significant. These results suggest that the LPS had increased the
      thermal set point in the old rats, but they could develop febrile responses only
      at the warm T(a) they selected.

PMID- 11294769
TI  - Acupuncture effects on reflex responses to mental stress in humans.
AB  - In animal studies, acupuncture has been shown to be sympathoinhibitory, but it is
      unknown if acupuncture is sympathoinhibitory in humans. Nineteen healthy
      volunteers underwent mental stress testing pre- and postacupuncture. Muscle
      sympathetic nerve activity (MSNA), blood pressure, and heart rate during mental
      stress were compared pre- and postacupuncture. Control acupuncture consisted of
      acupuncture at nonacupoints and "no-needle" acupuncture. Acupuncture had no
      effect on resting MSNA, blood pressure, or heart rate. After real acupuncture,
      the increase in mean arterial pressure (pre- vs. postacupuncture 4.5 vs. 1.7
      mmHg, P < 0.001), but not MSNA or heart rate, was blunted during mental stress.
      Similarly, following nonacupoint acupuncture, the increase in mean arterial
      pressure was blunted during mental stress (5.4 vs. 2.9 mmHg, P < 0.0003). No
      needle acupuncture had no effect on these variables. In conclusion, acupuncture
      at traditional acupoints, nonacupoints, and no-needle acupuncture does not
      modulate baseline MSNA or MSNA responses to mental stress in normal humans.
      Acupuncture significantly attenuates the increase in blood pressure during mental
      stress. Needling nonacupoints, but not "no-needle" acupuncture, have a similar
      effect on blood pressure.

PMID- 11294770
TI  - Recovery of force during postcontractile depression in single Xenopus muscle
      fibers.
AB  - This study examined the relationship between force and cytosolic free calcium
      concentration ([Ca2+]c) in different fiber types from Xenopus before, during, and
      after cells underwent postcontractile depression (PCD). During a standardized
      fatigue run, force in the two fast fatiguing (FF) fiber types (types 1 and 2, n =
      10) fell more quickly (5.8 vs. 8.1 min) and to a greater degree [0.36 vs. 0.51 of
      initial (P(o))] than in the slow fatiguing (SF) fiber type (type 3, n = 11).
      After the initial fatigue run, both FF and SF experienced a drop in force to <15%
      P(o) (PCD) at a similar time (20.6 vs. 21.4 min). A second stimulation period,
      undertaken during PCD, produced significant recovery of force in both groups, but
      significantly more so in SF than FF (64 +/- 7 vs. 29 +/- 2% P(o)). This force
      recovery during PCD was accompanied by a significant increase in peak [Ca2+]c,
      particularly in SF. However, despite the significant recovery of force during
      stimulation while in PCD, the amount of force produced for a given peak [Ca2+]c
      was significantly lower in both groups during PCD than at any other point in the
      experiment. A final stimulation period, initiated when all fibers had recovered
      from PCD, demonstrated a recovery of both force and peak [Ca2+]c in both groups,
      but this recovery was significantly greater in SF vs. FF. These data demonstrate
      that with continuous electrical stimulation, it is possible to produce a
      significant recovery of force production during the normally quiescent period of
      PCD, but that it occurs with a decreased muscle force production for a given peak
      [Ca2+]c. This suggests that factors other than structural alterations of the
      sarcoplasmic reticulum are likely the cause of PCD in these fibers.

PMID- 11294771
TI  - Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a
      melatonin receptor antagonist.
AB  - In addition to marked seasonal changes in reproductive, metabolic, and other
      physiological functions, many vertebrate species undergo seasonal changes in
      immune function. Despite growing evidence that photoperiod mediates seasonal
      changes in immune function, little is known regarding the neuroendocrine
      mechanisms underlying these changes. Increased immunity in short days is
      hypothesized to be due to the increase in the duration of nightly melatonin
      secretion, and recent studies indicate that melatonin acts directly on immune
      cells to enhance immune parameters. The present study examined the contribution
      of melatonin receptors in mediating the enhancement of splenocyte proliferation
      in response to the T cell mitogen Concanavalin A in mice. The administration of
      luzindole, a high-affinity melatonin receptor antagonist, either in vitro or in
      vivo significantly attenuated the ability of in vitro melatonin to enhance
      splenic lymphocyte proliferation during the day or night. In the absence of
      melatonin or luzindole, splenocyte proliferation was intrinsically higher during
      the night than during the day. In the absence of melatonin administration,
      luzindole reduced the ability of spleen cells to proliferate during the night,
      when endogenous melatonin concentrations are naturally high. This effect was not
      observed during the day, when melatonin concentrations are low. Taken together,
      these results suggest that melatonin enhancement of splenocyte proliferation is
      mediated directly by melatonin receptors on splenocytes and that there is diurnal
      variation in splenocyte proliferation in mice that is also mediated by splenic
      melatonin receptors.

PMID- 11294772
TI  - Hemodynamic and hormonal effects of human ghrelin in healthy volunteers.
AB  - To investigate hemodynamic and hormonal effects of ghrelin, a novel growth
      hormone (GH)-releasing peptide, we gave six healthy men an intravenous bolus of
      human ghrelin (10 microg/kg) or placebo and vice versa 1-2 wk apart in a
      randomized fashion. Ghrelin elicited a marked increase in circulating GH (15
      fold). The elevation of GH lasted longer than 60 min after the bolus injection.
      Injection of ghrelin significantly decreased mean arterial pressure (-12 mmHg, P
      < 0.05) without a significant change in heart rate (-4 beats/min, P = 0.39).
      Ghrelin significantly increased cardiac index (+16%, P < 0.05) and stroke volume
      index (+22%, P < 0.05). We also examined ghrelin receptor [GH secretagogues
      receptor (GHS-R)] gene expression in the aortas, the left ventricles, and the
      left atria of rats by RT-PCR. GHS-R mRNA was detectable in the rat aortas, left
      ventricles, and left atria, suggesting that ghrelin may cause cardiovascular
      effects through GH-independent mechanisms. In summary, human ghrelin elicited a
      potent, long-lasting GH release and had beneficial hemodynamic effects via
      reducing cardiac afterload and increasing cardiac output without an increase in
      heart rate.

PMID- 11294773
TI  - Molecular expression of myostatin and MyoD is greater in double-muscled than
      normal-muscled cattle fetuses.
AB  - Excessive muscling in double-muscled cattle arises from mutations in the
      myostatin gene, but the role of myostatin in normal muscle development is
      unclear. The aim of this study was to measure the temporal relationship of
      myostatin and myogenic regulatory factors during muscle development in normal
      (NM)- and double-muscled (DM) cattle to determine the timing and possible targets
      of myostatin action in vivo. Myostatin mRNA peaked at the onset of secondary
      fiber formation (P < 0.001) and was greater in DM (P < 0.001) than in NM. MyoD
      expression was also elevated throughout primary and secondary fiber formation (P
      < 0.001) and greater in DM (P < 0.05). Expression of myogenin peaked later than
      MyoD (P < 0.05); however, it did not differ between NM and DM. These data show
      that myostatin and MyoD increase coincidentally during formation of muscle
      fibers, indicating a coordinated role in the terminal differentiation and/or
      fusion of myoblasts. Myostatin mRNA is also consistently higher in DM than NM,
      suggesting that a feedback loop of regulation is also disrupted in the myostatin
      deficient condition.

PMID- 11294774
TI  - NO modulates norepinephrine release in human skeletal muscle: implications for
      neural preconditioning.
AB  - The purpose of this study was to estimate muscle interstitial norepinephrine (NE)
      levels during exercise and to determine whether nitric oxide (NO) modulates NE
      release in the skeletal muscle in humans. We measured interstitial dialysate
      concentrations of NE with two microdialysis probes inserted into the forearm.
      Probes were perfused with saline and the NO synthesis inhibitor N(G)-monomethyl-L
      arginine (L-NMMA), respectively. Dialysate samples were collected during two
      sequential 20-min intense dynamic handgrip periods, preceded by 40-min baseline
      periods. On a different day, forearm ischemia was performed instead of the first
      exercise period. Exercise increased dialysate NE from 172 +/- 42 to 270 +/- 45
      pg/ml (83% increase, P < 0.02, n = 6). Probes perfused with L-NMMA had a 136 +/-
      39% greater dialysate NE compared with probes perfused with saline (225 +/- 25
      vs. 125 +/- 25 pg/ml, P < 0.001, n = 9). The exercise-induced increase in NE (125
      +/- 52%) was attenuated if preceded by exercise (34 +/- 34%) or ischemia (40 +/-
      36%; P = 0.06, n = 6), suggesting a neural preconditioning effect. This
      attenuation was not observed in probes perfused with L-NMMA. We propose that NO
      modulates NE release in skeletal muscle, that ischemic exercise increases muscle
      interstitial NE, and that this increase can be attenuated by a preconditioning
      effect mediated in part by NO.

PMID- 11294775
TI  - Amniotic fluid and hemodynamic model in monochorionic twin pregnancies and twin
      twin transfusion syndrome.
AB  - We developed a mathematical model of monochorionic twin pregnancies and twin-twin
      transfusion syndrome (TTTS), combining both fetal fluid dynamics and
      fetoplacental growth and circulation alterations and assuming that transplacental
      fluid flow from mother to fetus accounts for normal fetal and amniotic fluid
      volumes. Ten coupled differential equations, describing fetal total body and
      amniotic fluid volumes, their osmolalities, and fetal blood colloid osmotic
      pressure, for both donor and recipient twins, were solved numerically. Amniotic
      flows are controlled by fetal plasma osmolality and hydrostatic and colloid
      osmotic pressures. We included varying placental anastomoses and placental
      sharing of the circulations. Consistent with clinical experience, model
      predictions are: fetofetal transfusion from unidirectional arteriovenous
      anastomoses cause oligo-polyhydramnios, a normal size recipient but hypovolemic
      donor; compensating oppositely directed deep and superficial anastomoses moderate
      discordant development; and anhydramnios results from mild and severe TTTS, where
      milder forms may even present earlier in gestation than severe TTTS. Unequal
      placental circulatory sharing may exacerbate discordant development. In
      conclusion, our model simulates a wide variety of realistic manifestations of
      amniotic fluid volume and fetal growth in TTTS related to placental
      angioarchitecture. The model may allow an assessment of the efficacy of current
      therapeutic interventions for TTTS.

PMID- 11294776
TI  - Evidence supporting a physiological role for proANP-(1-30) in the regulation of
      renal excretion.
AB  - The experiments, performed in pentobarbital sodium-anesthetized rats, consisted
      of a 1-h equilibration period followed by two 30-min control periods.
      Subsequently, synthetic rat pro atrial natriuretic peptide (ANP) [proANP-(1-30)]
      (n = 8) was given as a bolus of 10 microg in 1 ml of 0.9% saline followed by an
      infusion at 30 ng/min (20 microl/min) for six additional periods. Control rats (n
      = 6) received only 0.45% saline in the appropriate volumes. Mean arterial
      pressure, renal blood flow, and glomerular filtration rate did not change
      significantly in either group during the proANP-(1-30) infusion. Urine flow and
      potassium excretion increased approximately 50% in the proANP-(1-30)-infused
      group only (P < 0.05). Sodium excretion and fractional excretion of sodium,
      expressed as the change from their own baselines, were significantly increased by
      the proANP-(1-30) infusion (P < 0.05), whereas cGMP excretion was similar in both
      groups. These results suggest that the rat sequence of proANP-(1-30) produces a
      natriuresis in the rat independent of changes in hemodynamics and renal cGMP
      production. In a second study, rats (n = 8) were prepared as above and pretreated
      with 0.4 ml iv of rabbit serum containing an antibody directed against proANP-(1
      30) (anti-proANP group). The rats were volume expanded with 3 ml of 6% albumin in
      Krebs and observed for 3 h to determine if the anti-proANP would attenuate the
      responses to volume expansion. Control rats (n = 7) received 0.4 ml of normal
      rabbit serum. The elevation in potassium excretion in response to volume
      expansion was significantly attenuated in the anti-proANP group (P < 0.05).
      Sodium excretion and urine flow responses also tended to be reduced but not
      significantly. These results suggest that in the rat, proANP-(1-30) plays a
      physiological role in regulating renal excretion.

PMID- 11294777
TI  - Increased muscle ubiquitin mRNA levels in gastric cancer patients.
AB  - The intramuscular ATP-dependent ubiquitin (Ub)-proteasome proteolytic system is
      hyperactivated in experimental cancer cachexia. The present study aimed at
      verifying whether the expression of the muscle Ub mRNA is altered in patients
      with cancer. Total muscle RNA was extracted using the guanidinium
      isothiocyanate/phenol/chloroform method from rectus abdominis biopsies obtained
      intraoperatively from 20 gastric cancer (GC) patients and 10 subjects with benign
      abdominal diseases (CON) undergoing surgery. Ub mRNA levels were measured by
      northern blot analysis. Serum soluble tumor necrosis factor receptor (sTNFR) was
      measured by ELISA. Ub mRNA levels (arbitrary units, means +/- SD) were 2,345 +/-
      195 in GC and 1,162 +/- 132 in CON (P = 0.0005). Ub mRNA levels directly
      correlated with disease stage (r = 0.608, P = 0.005), being 1,945 +/- 786 in
      stages I and II, 2,480 +/- 650 in stage III, and 3,799 +/- 66 in stage IV. Ub
      mRNA and sTNFR did not correlate with age and nutritional parameters. This study
      confirms experimental data indicating an overexpression of muscle Ub mRNA in
      cancer cachexia. Lack of correlation with nutritional status suggests that Ub
      activation in human cancer is an early feature that precedes any clinical sign of
      cachexia.

PMID- 11294778
TI  - Renal tubular sites of increased phosphate transport and NaPi-2 expression in the
      juvenile rat.
AB  - To determine the tubular sites and mechanisms involved in enhanced renal
      phosphate (P(i)) reabsorption seen in the juvenile animal, renal micropuncture
      experiments were performed in acutely thyroparathyroidectomized adult (>14 wk
      old) and juvenile (4 wk old) male Wistar rats fed either a normal P(i) diet (NPD,
      0.6% P(i)) or low P(i) diet (0.07% P(i)) for 2 days, in the presence and absence
      of parathyroid hormone (PTH). P(i) reabsorption was greater in proximal
      convoluted (PCT) and straight tubules (PST) of the juvenile compared with adult
      rats fed NPD, whether or not PTH was present. These findings were consistent with
      a greater P(i) uptake in brush-border membrane (BBM) vesicles from both
      superficial (SC) and outer juxtamedullary (JMC) cortices of juvenile animals.
      Western blot analysis revealed a 2- and 1.8-fold higher amount of NaPi-2 protein
      in the SC and JMC, respectively, in juvenile rats. Immunofluorescence microscopy
      also indicated that NaPi-2 protein expression was present in the proximal tubule
      (PT) BBM to a greater extent in juvenile rats. Dietary P(i) restriction in
      juvenile rats resulted in a significant increase in P(i) reabsorption in the PCT
      and PST segments. NaPi-2 expression in the PT BBM was also increased, as was the
      expression of intracellular NaPi-2 protein. These studies indicate that P(i)
      reabsorption in both the PCT and PST segments of the renal tubule contributes to
      the attenuated response to PTH in the normal juvenile animal. In addition,
      dietary P(i) restriction in the juvenile rat upregulates BBM NaPi-2 expression,
      which is associated with a further increase in proximal tubular P(i)
      reabsorption.

PMID- 11294779
TI  - Long-term control of renal blood flow: what is the role of the renal nerves?
AB  - We have developed a system for long-term continuous monitoring of cardiovascular
      parameters in rabbits living in their home cage to assess what role renal
      sympathetic nerve activity (RSNA) has in regulating renal blood flow (RBF) in
      daily life. Blood pressure, heart rate, locomotor activity, RSNA, and RBF were
      recorded continuously for 4 wk. Beginning 4-5 days after surgery a circadian
      rhythm, dependent on feeding time, was observed. When averaged over all days RBF
      to the innervated and denervated kidneys was not significantly different.
      However, control of RBF around these mean levels was dependent on the presence of
      the renal sympathetic nerves. In particular we observed episodic elevations in
      heart rate and other parameters associated with activity. In the denervated
      kidney, during these episodic elevations, the increase in renal resistance was
      closely related to the increase in arterial pressure. In the innervated kidney
      the renal resistance response was significantly more variable, indicating an
      interaction of the sympathetic nervous system. These results indicate that
      whereas overall levels of RSNA do not set the mean level of RBF the renal
      vasculature is sensitive to episodic increases in sympathetic nerve activity.

PMID- 11294780
TI  - E2 and not P4 increases NO release from NANC nerves of the gastrointestinal
      tract: implications in pregnancy.
AB  - In women, during pregnancy, there is decreased motility of the gastrointestinal
      tract leading to a delay in gastric emptying and an increase in colonic transit
      time. Whether the rise in estradiol (E2) or progesterone (P4) is responsible for
      this effect is controversial. As the nitrergic component of the nonadrenergic,
      noncholinergic (NANC) nerves is responsible for modulating gastrointestinal
      motility in vivo, the purpose of this study was to evaluate whether the increased
      release of nitric oxide (NO) from the nitrergic component of the NANC nerves
      innervating the gastric fundus and colon that occurs during late pregnancy in
      rats is mediated by E2 or P4. Ovariectomized rats treated with E2 or P4 alone or
      in combination were used for our studies. We also wanted to assess the cellular
      and molecular mechanisms involved. The NANC activity was studied by assessing
      changes in tone after application of electric field stimulation (EFS). The role
      of NO was determined by observing the effects of EFS in the presence and absence
      of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME)
      and the reversibility of the effects of L-NAME by L-arginine. Our studies
      indicated that there was increased magnitude of relaxation of isolated strips of
      rat gastric fundus and rat colon after application of EFS to tissues obtained
      from animals treated with E2 alone or a combination of E2 + P4 but not from those
      treated with P4 alone. L-NAME attenuated relaxation responses in E2- and E2 + P4
      treated animals. To elucidate whether the increased NO release may be due to an
      increase in neuronal NOS (nNOS) protein, we used both Western blot analysis and
      immunohistochemistry. We also used RT-PCR to determine whether there was an
      increase in nNOS mRNA after treatment with sex steroids. In nonpregnant animals,
      nNOS was detected by Western blot in the fundus and the colon and was barely
      detectable in the ileum. In pregnancy, there was an increase in nNOS in both the
      gastric fundus and the colon. The nNOS protein was also increased in
      ovariectomized animals treated with either E2 alone or E2 + P4 but not P4 alone
      when compared with ovariectomized animals receiving vehicle. Our results
      indicated that there was an increase in nNOS protein that was localized to the
      neurons of the myenteric plexus in the gastric fundus and colon in E2- and E2 +
      P4-treated animals, but this increase was not observed in animals treated with P4
      alone. This increase in nNOS protein was accompanied by an increase in nNOS mRNA.
      These results suggest the possibility that E2, rather than P4, may be responsible
      for the delay in gastric emptying and increase in colonic transit time observed
      in pregnancy.

PMID- 11294781
TI  - Cell cycle progression and cell division are sensitive to hypoxia in Drosophila
      melanogaster embryos.
AB  - We and others recently demonstrated that Drosophila melanogaster embryos arrest
      development and embryonic cells cease dividing when they are deprived of O2. To
      further characterize the behavior of these embryos in response to O2 deprivation
      and to define the O2-sensitive checkpoints in the cell cycle, embryos undergoing
      nuclear cycles 3-13 were subjected to O2 deprivation and examined by confocal
      microscopy under control, hypoxic, and reoxygenation conditions. In vivo, real
      time analysis of embryos carrying green fluorescent protein-kinesin demonstrated
      that cells arrest at two major points of the cell cycle, either at the interphase
      (before DNA duplication) or at metaphase, depending on the cell cycle phase at
      which O2 deprivation was induced. Immunoblot analysis of embryos whose cell
      divisions are synchronized by inducible String (cdc25 homolog) demonstrated that
      cyclin B was degraded during low O2 conditions in interphase-arrested embryos but
      not in those arrested in metaphase. Embryos resumed cell cycle activity within
      ~20 min of reoxygenation, with very little apparent change in cell cycle
      kinetics. We conclude that there are specific points during the embryonic cell
      cycle that are sensitive to the O2 level in D. melanogaster. Given the fact that
      O2 deprivation also influences the growth and development of other species, we
      suggest that similar hypoxia-sensitive cell cycle checkpoints may also exist in
      mammalian cells.

PMID- 11294782
TI  - Splenic denervation worsens lipopolysaccharide-induced hypotension,
      hemoconcentration, and hypovolemia.
AB  - During lipopolysaccharide (LPS)-induced endotoxemia, increased intrasplenic fluid
      efflux contributes to a reduction in plasma volume. We hypothesized that splenic
      sympathetic nerve activity (SSNA), which increases during endotoxemia, limits
      intrasplenic fluid efflux. We reasoned that splenic denervation would exaggerate
      LPS-induced intrasplenic fluid efflux and worsen the hypotension,
      hemoconcentration, and hypovolemia. A nonlethal dose of LPS (150 microg x kg(-1)
      x h(-1) for 18 h) was infused into conscious male rats bearing transit time flow
      probes on the splenic artery and vein. Fluid efflux was estimated from the
      difference in splenic arterial inflow and venous outflow (A-V). LPS significantly
      increased the (A-V) flow differential (fluid efflux) in intact rats (saline -0.01
      +/- 0.02 ml/min, n = 8 vs. LPS +0.21 +/- 0.06 ml/min, n = 8); this was
      exaggerated in splenic denervated rats (saline -0.03 +/- 0.01 ml/min, n = 7 vs.
      LPS +0.41 +/- 0.08 ml/min, n = 8). Splenic denervation also exacerbated the LPS
      induced hypotension, hemoconcentration, and hypovolemia (peak fall in mean
      arterial pressure: denervated 19 +/- 3 mmHg, n = 10 vs. intact 12 +/- 1 mmHg, n =
      8; peak rise in hematocrit: denervated 6.7 +/- 0.3%, n = 8 vs. intact 5.0 +/-
      0.3%, n = 8; decrease in plasma volume at 90-min post-LPS infusion: denervated
      1.08 +/- 0.15 ml/100 g body wt, n = 7 vs. intact 0.54 +/- 0.08 ml/100 g body wt,
      n = 8). The exaggerated LPS-induced hypovolemia associated with splenic
      denervation was mirrored in the rise in plasma renin activity (90 min post-LPS:
      denervated 11.5 +/- 0.8 ng x ml(-1) x h(-1), n = 9 vs. intact 6.6 +/- 0.7 ng x
      ml(-1) x h(-1), n = 8). These results are consistent with our proposal that SSNA
      normally limits LPS-induced intrasplenic fluid efflux.

PMID- 11294783
TI  - Intracranial pressure accommodation is impaired by blocking pathways leading to
      extracranial lymphatics.
AB  - Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur
      through the cribriform plate into the nasal submucosa, where it is absorbed by
      cervical lymphatics. We tested the hypothesis that sealing the cribriform plate
      extracranially would impair the ability of the CSF pressure-regulating systems to
      compensate for volume infusions. Sheep were challenged with constant flow or
      constant pressure infusions of artificial CSF into the CSF compartment before and
      after the nasal mucosal side of the cribriform plate was sealed. With both
      infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships
      were shifted significantly to the left when the cribriform plate was blocked.
      This indicated that obstruction of the cribriform plate reduced CSF clearance.
      Sham surgical procedures had no significant effects. Estimates of the
      proportional flow through cribriform and noncribriform routes suggested that
      cranial CSF absorption occurred primarily through the cribriform plate at low
      ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways)
      appeared to be recruited only when intracranial pressures were elevated. These
      data challenge the conventional view that CSF is absorbed principally via
      arachnoid villi and provide further support for the existence of several
      anatomically distinct cranial CSF transport pathways.

PMID- 11294784
TI  - Melatonin or a melatonin agonist corrects age-related changes in circadian
      response to environmental stimulus.
AB  - The effects of a melatonin agonist, S-20098, included in the diet were tested on
      a specific effect of aging in hamsters: the marked decline in the phase shifting
      effects of a 6-h pulse of darkness on a background of constant light. In contrast
      to young hamsters, old hamsters fed with the control diet showed little or no
      phase shifts in response to a dark pulse presented in the middle of their
      inactive or active period. Old hamsters fed with S-20098 showed phase shifts that
      were ~70% of the ones in young animals and significantly greater than those in
      old controls. The phase advancing response to a dark pulse presented during the
      inactive period was dose dependent and reversed after S-20098 discontinuation.
      Melatonin included in the diet showed comparable restorative effects on the phase
      shifting response to a dark pulse in old hamsters. Replacement therapy with
      melatonin or melatonin-related compounds could prove useful in treating,
      preventing, or delaying disturbances of circadian rhythmicity and/or sleep in
      older people.

PMID- 11294785
TI  - Agonist activation of cytosolic Ca2+ in subfornical organ cells projecting to the
      supraoptic nucleus.
AB  - The subfornical organ (SFO) is sensitive to both ANG II and ACh, and local
      application of these agents produces dipsogenic responses and vasopressin
      release. The present study examined the effects of cholinergic drugs, ANG II, and
      increased extracellular osmolarity on dissociated, cultured cells of the SFO that
      were retrogradely labeled from the supraoptic nucleus. The effects were measured
      as changes in cytosolic calcium in fura 2-loaded cells by using a calcium imaging
      system. Both ACh and carbachol increased intracellular ionic calcium
      concentration ([Ca2+]i). However, in contrast to the effects of muscarinic
      receptor agonists on SFO neurons, manipulation of the extracellular osmolality
      produced no effects, and application of ANG II produced only moderate effects on
      [Ca2+]i in a few retrogradely labeled cells. The cholinergic effects on [Ca2+]i
      could be blocked with the muscarinic receptor antagonist atropine and with the
      more selective muscarinic receptor antagonists pirenzepine and 4-diphenylacetoxy
      N-methylpiperdine methiodide (4-DAMP). In addition, the calcium in the
      extracellular fluid was required for the cholinergic-induced increase in [Ca2+]i.
      These findings indicate that ACh acts to induce a functional cellular response in
      SFO neurons through action on a muscarinic receptor, probably of the M1 subtype
      and that the increase of [Ca2+]i, at least initially, requires the entry of
      extracellular Ca2+. Also, consistent with a functional role of M1 receptors in
      the SFO are the results of immunohistochemical preparations demonstrating M1
      muscarinic receptor-like protein present within this forebrain circumventricular
      organ.

PMID- 11294786
TI  - Physical mapping with automatic capture of hybridization data.
AB  - MOTIVATION: Contig maps are a type of physical map that show the native order of
      a set of overlapping genomic clones. Overlaps between clones can be detected by
      finding common sequences using a number of experimental protocols including
      hybridization of probes. All current mapping algorithms of which we are aware
      require that hybridizations be scored using a fixed number of discrete values
      (typically 0/1 or high/medium/low). When hybridization data is captured
      automatically using digital equipment, this provides the opportunity for
      hybridization intensities to be used in map construction. More fine-grained
      distinctions in the levels of hybridization may be exploited by algorithms to
      generate more accurate physical maps. RESULTS: We describe an approach to
      creating contig maps that uses measured hybridization intensities instead of data
      scored with a fixed number of discrete values. We describe and compare four
      algorithms for creating physical maps with hybridization intensities. Simulations
      using measured intensities sampled from actual data on Aspergillus nidulans
      indicate that using hybridization intensities rather than data that is
      automatically scored with respect to threshold values may yield more accurate
      physical maps.

PMID- 11294787
TI  - Efficient primer design algorithms.
AB  - MOTIVATION: Primer design involves various parameters such as string-based
      alignment scores, melting temperature, primer length and GC content. This entails
      a design approach from multicriteria decision making. Values of some of the
      criteria are easy to compute while others require intense calculations. RESULTS:
      The reference point method was found to be tractable for trading-off between
      deviations from ideal values of all the criteria. Some criteria computations are
      based on dynamic programs with value iteration whose run time can be bounded by a
      low-degree polynomial. For designing standard PCR primers, the scheme offers in a
      relative gain in computing speed of up to 50: 1 over ad-hoc computational
      methods. Single PCR primer pairs have been used as model systems in order to
      simplify the quantization of the computational acceleration factors. The program
      has been structured so as to facilitate the analysis of large numbers of primer
      pairs with minor modifications. The scheme significantly increases primer design
      throughput which in turn facilitates the use of oligonucleotides in a wide range
      of applications including: multiplex PCR and other nucleic acid-based
      amplification systems, as well as in zip code targeting, oligonucleotide
      microarrays and nucleic acid-based nanoengineering.

PMID- 11294788
TI  - Basic Gene Grammars and DNA-ChartParser for language processing of Escherichia
      coli promoter DNA sequences.
AB  - MOTIVATION: The field of 'DNA linguistics' has emerged from pioneering work in
      computational linguistics and molecular biology. Most formal grammars in this
      field are expressed using Definite Clause Grammars but these have computational
      limitations which must be overcome. The present study provides a new DNA parsing
      system, comprising a logic grammar formalism called Basic Gene Grammars and a
      bidirectional chart parser DNA-ChartParser. RESULTS: The use of Basic Gene
      Grammars is demonstrated in representing many formulations of the knowledge of
      Escherichia coli promoters, including knowledge acquired from human experts,
      consensus sequences, statistics (weight matrices), symbolic learning, and neural
      network learning. The DNA-ChartParser provides bidirectional parsing facilities
      for BGGs in handling overlapping categories, gap categories, approximate pattern
      matching, and constraints. Basic Gene Grammars and the DNA-ChartParser allowed
      different sources of knowledge for recognizing E.coli promoters to be combined to
      achieve better accuracy as assessed by parsing these DNA sequences in real-world
      data sets.

PMID- 11294789
TI  - Flexibility of the genetic code with respect to DNA structure.
AB  - MOTIVATION: The primary function of DNA is to carry genetic information through
      the genetic code. DNA, however, contains a variety of other signals related, for
      instance, to reading frame, codon bias, pairwise codon bias, splice sites and
      transcription regulation, nucleosome positioning and DNA structure. Here we study
      the relationship between the genetic code and DNA structure and address two
      questions. First, to which degree does the degeneracy of the genetic code and the
      acceptable amino acid substitution patterns allow for the superimposition of DNA
      structural signals to protein coding sequences? Second, is the origin or
      evolution of the genetic code likely to have been constrained by DNA structure?
      RESULTS: We develop an index for code flexibility with respect to DNA structure.
      Using five different di- or tri-nucleotide models of sequence-dependent DNA
      structure, we show that the standard genetic code provides a fair level of
      flexibility at the level of broad amino acid categories. Thus the code generally
      allows for the superimposition of any structural signal on any protein-coding
      sequence, through amino acid substitution. The flexibility observed at the level
      of single amino acids allows only for the superimposition of punctual and loosely
      positioned signals to conserved amino acid sequences. The degree of flexibility
      of the genetic code is low or average with respect to several classes of
      alternative codes. This result is consistent with the view that DNA structure is
      not likely to have played a significant role in the origin and evolution of the
      genetic code.

PMID- 11294790
TI  - MetaFam: a unified classification of protein families. I. Overview and
      statistics.
AB  - MOTIVATION: Protein sequence classification is becoming an increasingly important
      means of organizing the voluminous data produced by large-scale genome sequencing
      projects. At present, there are several independent classification methods. To
      aid the general classification effort, we have created a unified protein family
      resource, MetaFam. MetaFam is a protein family classification built upon 10
      publicly-accessible protein family databases (Blocks + DOMO, Pfam, PIR-ALN,
      PRINTS, PROSITE, ProDom, PROTOMAP, SBASE, and SYSTERS). MetaFam's family
      'supersets', as we call them, are created automatically using set-theory to
      compare families among the databases. Families of one database are matched to
      those in another when the intersection of their members exceeds all other
      possible family pairings between the two databases. Pairwise family matches are
      drawn together transitively to create a new list of protein family supersets.
      RESULTS: MetaFam family supersets have several useful features: (1) each superset
      contains more members than the families from which it is composed, because each
      of the component family databases only works with a subset of our full non
      redundant set of proteins; (2) conflicting assignments can be pinpointed quickly,
      since our analysis identifies individual members that are in conflict with the
      majority consensus; (3) family descriptions that are absent from automated
      databases can frequently be assigned; (4) statistics have been computed comparing
      domain boundaries, family size distributions, and overall quality of MetaFam
      supersets; (5) the supersets have been loaded into a relational database to allow
      for complex queries and visualization of the connections among families in a
      superset and the consensus of individual domain members; and (6) the quality of
      individual supersets has been assessed using numerous quantitative measures such
      as family consistency, connectedness, and size. We anticipate this new resource
      will be particularly useful to genomic database curators.

PMID- 11294791
TI  - MetaFam: a unified classification of protein families. II. Schema and query
      capabilities.
AB  - MOTIVATION: Protein sequence and family data is accumulating at such a rapid rate
      that state-of-the-art databases and interface tools are required to aid curators
      with their classifications. We have designed such a system, MetaFam, to
      facilitate the comparison and integration of public protein sequence and family
      data. This paper presents the global schema, integration issues, and query
      capabilities of MetaFam. RESULTS: MetaFam is an integrated data warehouse of
      information about protein families and their sequences. This data has been
      collected into a consistent global schema, and stored in an Oracle relational
      database. The warehouse implementation allows for quick removal of outdated data
      sets. In addition to the relational implementation of the primary schema, we have
      developed several derived tables that enable efficient access from data
      visualization and exploration tools. Through a series of straightforward SQL
      queries, we demonstrate the usefulness of this data warehouse for comparing
      protein family classifications and for functional assignment of new sequences.

PMID- 11294792
TI  - Picasso: generating a covering set of protein family profiles.
AB  - MOTIVATION: Evolutionary classification leads to an economical description of
      protein sequence data because attributes of function and structure are inherited
      in protein families. This paper presents Picasso, a procedure for deriving a
      minimal set of protein family profiles that cover all known protein sequences.
      RESULTS: Picasso starts from highly overlapping sequence neighbourhoods revealed
      by all-on-all pairwise Blast alignment. Overlaps are reduced by merging sequences
      or parts of sequences into multiple alignments. For maximum unification, the
      multiple alignments must reach into the twilight zone of sequence similarity.
      Sensitive and selective profile-profile comparison allows unification down to
      about 15% pairwise sequence identity. Families unified through a short conserved
      sequence motif are associated with multiple full-length alignments describing
      different subfamilies. Domains that are mobile modules are identified based on
      their association with different sets of neighbours. The result is 10000 unified
      domain families (excluding singletons) representing functionally related proteins
      and recovering classical prolific domain types in high numbers. The
      classification is useful, for example, in developing strategies for efficient
      database searching and for selecting targets to complete the map of all 3-D
      structures.

PMID- 11294793
TI  - Genview and Gencode : a pair of programs to test theories of genetic code
      evolution.
AB  - GENVIEW: and GENCODE: are tools for testing the adaptive nature of a genetic code
      under different assumptions about patterns of genetic error and the nature of
      amino acid similarity. GENVIEW: provides a user friendly, point-and-click
      interface by which a user may reproduce and extend analysis of the adaptive
      properties of the standard genetic code or any of its secondary derivatives.
      GENVIEW: is a graphical user interface (GUI) program which runs on Linux, Unix
      and Microsoft Windows platforms and is based on the GTKf + toolkit. GENVIEW:
      outputs ASCII configuration files which are interpreted by GENCODE: to perform an
      analysis. GENCODE: is available for the same platforms as GENVIEW.

PMID- 11294794
TI  - Clustering of highly homologous sequences to reduce the size of large protein
      databases.
AB  - We present a fast and flexible program for clustering large protein databases at
      different sequence identity levels. It takes less than 2 h for the all-against
      all sequence comparison and clustering of the non-redundant protein database of
      over 560,000 sequences on a high-end PC. The output database, including only the
      representative sequences, can be used for more efficient and sensitive database
      searches.

PMID- 11294795
TI  - ASEdb: a database of alanine mutations and their effects on the free energy of
      binding in protein interactions.
AB  - The Alanine Scanning Energetics database (ASEdb) is a searchable database of
      single alanine mutations in protein-protein, protein-nucleic acid, and protein
      small molecule interactions for which binding affinities have been experimentally
      determined. In cases where structures are available, it contains surface areas of
      the mutated side chain and links to the PDB entries. It is useful for studying
      the contribution of single amino acids to the energetics of protein interactions,
      and can be updated by researchers as new data are generated.

PMID- 11294796
TI  - Dynamic simulation of the human red blood cell metabolic network.
AB  - We have developed a Mathematica application package to perform dynamic
      simulations of the red blood cell (RBC) metabolic network. The package relies on,
      and integrates, many years of mathematical modeling and biochemical work on red
      blood cell metabolism. The extensive data regarding the red blood cell metabolic
      network and the previous kinetic analysis of all the individual components makes
      the human RBC an ideal 'model' system for mathematical metabolic models. The
      Mathematica package can be used to understand the dynamics and regulatory
      characteristics of the red blood cell.

PMID- 11294797
TI  - MEG (Model Extender for Gepasi): a program for the modelling of complex,
      heterogeneous, cellular systems.
AB  - SUMMARY: We describe a program for the construction of spatially distributed
      metabolic models, which may then be simulated using the metabolic simulator
      GEPASI: This is useful for the modelling of heterogeneous systems whether as
      liquid cultures or as spatially organised systems with specified
      interconnections.

PMID- 11294798
TI  - Intravascular sonotherapy decreases neointimal hyperplasia after stent
      implantation in swine.
AB  - BACKGROUND: Intimal hyperplasia and subsequent in-stent restenosis remain a major
      limitation after stent implantation. In vitro cell culture studies show that low
      frequency, noncavitational ultrasound energy may impact smooth muscle cell
      proliferation. Accordingly, we assessed the efficacy of intravascular sonotherapy
      treatment on intimal hyperplasia in a swine stent model. METHODS AND RESULTS:
      After balloon injury, biliary stents (Johnson & Johnson) were implanted in the
      femoral arteries of 14 swine. A total of 48 stented sites were randomized to
      sonotherapy or sham treatment using a custom-built, 8-French catheter
      intravascular sonotherapy system (URX, PharmaSonics Inc). After stent deployment,
      ultrasound energy (700 KHz) was applied to the treatment group for up to 5
      minutes. Smooth muscle cell proliferation was assessed using bromodeoxyuridine
      histology preparation (BrdU) at 7 days in 28 stented sites. At 28 days, the
      neointimal thickness and the ratio of neointimal/stent area (percent stenosis)
      was calculated by histomorphometric quantification in 20 stented sites. At 7
      days, percent of BrdU staining was significantly reduced in the sonotherapy group
      compared with the sham group (24.1+/-7.0% versus 31.2+/-3.0%, P<0.05). At 28
      days, percent stenosis was significantly less in the sonotherapy group than in
      the sham group (36+/-24% versus 44+/-27%, P<0.05), and the mean neointimal
      thickness in the sonotherapy group was less than in the sham group (417+/-461
      micrometer versus 643+/-869 micrometer, P=0.06). CONCLUSIONS: In this swine
      peripheral model, intravascular sonotherapy seemed to decelerate cellular
      proliferation and decrease in-stent hyperplasia. Therefore, intravascular
      sonotherapy may be an effective form of nonionizing energy to reduce in-stent
      restenosis.

PMID- 11294799
TI  - Bedside multimarker testing for risk stratification in chest pain units: The
      chest pain evaluation by creatine kinase-MB, myoglobin, and troponin I
      (CHECKMATE) study.
AB  - BACKGROUND: Earlier, rapid evaluation in chest pain units may make patient care
      more efficient. A multimarker strategy (MMS) testing for several markers of
      myocardial necrosis with different time-to-positivity profiles also may offer
      clinical advantages. METHODS AND RESULTS: We prospectively compared bedside
      quantitative multimarker testing versus local laboratory results (LL) in 1005
      patients in 6 chest pain units. Myoglobin, creatine kinase-MB, and troponin I
      were measured at 0, 3, 6, 9 to 12, and 16 to 24 hours after admission. Two MMS
      were defined: MMS-1 (all 3 markers) and MMS-2 (creatine kinase-MB and troponin I
      only). The primary assessment was to relate marker status with 30-day death or
      infarction. More patients were positive by 24 hours with MMS than with LL (MMS-1,
      23.9%; MMS-2, 18.8%; LL, 8.8%; P=0.001, all comparisons), and they became
      positive sooner with MMS-1 (2.5 hours, P=0.023 versus LL) versus MMS-2 (2.8
      hours, P=0.026 versus LL) or LL (3.4 hours). The relation between baseline MMS
      status and 30-day death or infarction was stronger (MMS-1: positive, 18.8% event
      rate versus negative, 3.0%, P=0.001; MMS-2: 21.9% versus 3.2%, P=0.001) than that
      for LL (13.6% versus 5.5%, P=0.038). MMS-1 discriminated 30-day death better
      (positive, 2.0% versus negative, 0.0%, P=0.007) than MMS-2 (positive, 1.8% versus
      negative, 0.2%; P=0.055) or LL (positive, 0.0% versus negative, 0.5%; P=1.000).
      CONCLUSIONS: Rapid multimarker analysis identifies positive patients earlier and
      provides better risk stratification for mortality than a local laboratory-based,
      single-marker approach.

PMID- 11294800
TI  - Argatroban anticoagulant therapy in patients with heparin-induced
      thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome
      caused by heparin. Complications range from thrombocytopenia to thrombocytopenia
      with thrombosis. We report a prospective, historical- controlled study evaluating
      the efficacy and safety of argatroban, a direct thrombin inhibitor, as
      anticoagulant therapy in patients with HIT or HIT with thrombosis syndrome
      (HITTS). METHODS AND RESULTS: Patients with HIT (isolated thrombocytopenia,
      n=160) or HITTS (n=144) received 2 microgram. kg(-1). min(-1) IV argatroban,
      adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times
      baseline value. Treatment was maintained for 6 days, on average. Clinical
      outcomes over 37 days were compared with those of 193 historical control subjects
      with HIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end
      point, a composite of all-cause death, all-cause amputation, or new thrombosis,
      was reduced significantly in argatroban-treated patients versus control subjects
      with HIT (25.6% versus 38.8%, P=0.014). In HITTS, the composite incidence in
      argatroban-treated patients was 43.8% versus 56.5% in control subjects (P=0.13).
      Significant between-group differences by time-to-event analysis of the composite
      end point favored argatroban treatment in HIT (P=0.010) and HITTS (P=0.014).
      Argatroban therapy, relative to control subjects, also significantly reduced new
      thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients
      achieved therapeutic activated partial thromboplastin times generally within 4 to
      5 hours of starting therapy and, compared with control subjects, had a
      significantly more rapid rise in platelet counts (P=0.0001). Bleeding events were
      similar between groups. CONCLUSIONS: Argatroban anticoagulation, compared with
      historical control subjects, improves clinical outcomes in patients who have
      heparin-induced thrombocytopenia, without increasing bleeding risk.

PMID- 11294801
TI  - Decreased expression of tumor necrosis factor-alpha and regression of hypertrophy
      after nonsurgical septal reduction therapy for patients with hypertrophic
      obstructive cardiomyopathy.
AB  - BACKGROUND: Nonsurgical septal reduction therapy (NSRT) is a novel therapeutic
      strategy for patients with hypertrophic obstructive cardiomyopathy (HOCM).
      Although the clinical benefits of this technique appear to be clear, the
      structural and functional changes that lead to improvements in cardiac function
      are not completely defined. In these studies, we sought to define the effect of
      NSRT on myocardial function as well as various markers of hypertrophy including
      the expression of tumor necrosis factor (TNF)-alpha, a cytokine capable of
      producing fibrosis, left ventricular hypertrophy (LVH), and cardiomyopathy.
      METHODS AND RESULTS: We performed endomyocardial biopsies of the RV side of the
      septum and echocardiograms on 15 HOCM patients at baseline and after successful
      NSRT. Comparative analysis on paired myocardial samples were performed to
      determine the effects of NSRT on LVH, end-diastolic volume and chamber stiffness,
      myocyte size, collagen content, and TNF-alpha levels. At baseline, myocardial TNF
      alpha levels were increased in all patients. After NSRT, myocyte size, collagen
      content, and TNF-alpha were significantly decreased. These changes were
      accompanied by an increase in left ventricular volumes and a reduction in LVH and
      chamber stiffness. CONCLUSIONS: We suggest that pressure overload in HOCM
      patients contributes to the development of hypertrophy. These data provide the
      initial experimental evidence to suggest that TNF-alpha may play a pathogenetic
      role in the hypertrophy of pressure overload.

PMID- 11294802
TI  - Deterioration of left ventricular chamber performance after bed rest :
      "cardiovascular deconditioning" or hypovolemia?
AB  - BACKGROUND: Orthostatic intolerance after bed rest is characterized by
      hypovolemia and an excessive reduction in stroke volume (SV) in the upright
      position. We studied whether the reduction in SV is due to a specific adaptation
      of the heart to head-down tilt bed rest (HDTBR) or acute hypovolemia alone.
      METHODS AND RESULTS: We constructed left ventricular (LV) pressure-volume curves
      from pulmonary capillary wedge pressure and LV end-diastolic volume and Starling
      curves from pulmonary capillary wedge pressure and SV during lower body negative
      pressure and saline loading in 7 men (25+/-2 years) before and after 2 weeks of 
      6 degrees HDTBR and after the acute administration of intravenous furosemide.
      Both HDTBR and hypovolemia led to a similar reduction in plasma volume. However,
      baseline LV end-diastolic volume decreased by 20+/-4% after HDTBR and by 7+/-2%
      after hypovolemia (interaction P<0.001). Moreover, SV was reduced more and the
      Starling curve was steeper during orthostatic stress after HDTBR than after
      hypovolemia. The pressure-volume curve showed a leftward shift and the
      equilibrium volume of the left ventricle was decreased after HDTBR; however,
      after hypovolemia alone, the curve was identical, with no change in equilibrium
      volume. Lower body negative pressure tolerance was reduced after both conditions;
      it decreased by 27+/-7% (P<0.05) after HDTBR and by 18+/-8% (P<0.05) after
      hypovolemia. CONCLUSIONS: Chronic HDTBR leads to ventricular remodeling, which is
      not seen with equivalent degrees of acute hypovolemia. This remodeling leads to a
      greater decrease in SV during orthostatic stress after bed rest than hypovolemia
      alone, potentially contributing to orthostatic intolerance.

PMID- 11294803
TI  - Saline-cooled versus standard radiofrequency catheter ablation for infarct
      related ventricular tachycardias.
AB  - BACKGROUND: Saline cooling of the electrode during radiofrequency (RF) ablation
      increases lesion size in animal models. If cooled RF also increases lesion size
      in human infarcts, it should facilitate the termination of ventricular
      tachycardia (VT). METHODS AND RESULTS: In 66 patients with VT due to prior
      infarction, 366 ablation sites, which were classified by entrainment and isolated
      potentials followed by ablation during VT with either standard RF energy (247
      sites) or cooled RF (119 sites), were retrospectively reviewed to compare the
      efficacy for terminating VT. RF energy was applied at 259 isthmus sites, 62
      bystander sites, 28 inner loop sites, and 17 outer loop sites. Compared with
      standard RF, cooled RF terminated VT more frequently at isthmus sites where an
      isolated potential was present (89% versus 54%, P=0.003), isthmus sites without
      an isolated potential (36% versus 21%, P=0.04), and at inner loop sites (60%
      versus 22%, P=0.04). Termination rates were similarly low for cooled and standard
      RF at bystander sites (14% versus 9%, P=0.56) and outer loop sites (13% versus
      11%, P=0.93). CONCLUSIONS: Greater efficacy of cooled RF for terminating VT is
      consistent with the production of a larger lesion in human infarctions, which
      should facilitate successful ablation.

PMID- 11294805
TI  - Elevated urinary albumin excretion is associated with impaired arterial dilatory
      capacity in clinically healthy subjects.
AB  - BACKGROUND: Elevated urinary albumin excretion (UAE) predicts atherosclerotic
      cardiovascular disease. It is hypothesized that elevated UAE is associated with a
      generalized vascular dysfunction. This study tested this hypothesis for conduit
      arteries. METHODS AND RESULTS: Clinically healthy subjects were selected: 19 with
      UAE >90th percentile in the background population (6.6 microgram/min<UAE<150
      microgram/min) and 41 with normoalbuminuria (UAE <6.6 microgram/min). External
      ultrasound was used to measure the dilatory response of the brachial artery to
      postischemic increased blood flow (endothelium-dependent, flow-associated
      dilation) and to nitroglycerin (endothelium-independent, nitroglycerin-induced
      dilation). Plasma concentrations of the endothelial markers nitrate/nitrite,
      thrombomodulin, and von Willebrand factor antigen were also measured. Both flow
      associated and nitroglycerin-induced dilations were significantly impaired in
      subjects with elevated UAE as compared with normoalbuminuric control subjects:
      102.0+/-1.0% (mean+/-SEM) versus 104.3+/-0.6% (P<0.05) and 120.1+/-1.5% versus
      123.8+/-1.0% (P<0.05). No differences in the plasma concentrations of endothelial
      markers were found. Conclusions-Slightly elevated UAE is associated with impaired
      conduit arterial dilatory capacity in clinically healthy subjects, and this
      impairment may be explained by a reduced dilatory response to nitric oxide of
      both endogenous and exogenous origin. Impaired arterial dilatory capacity may
      contribute to the increased cardiovascular risk in subjects with elevated UAE.

PMID- 11294804
TI  - Serum vitamin C concentration is low in peripheral arterial disease and is
      associated with inflammation and severity of atherosclerosis.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a severe atherosclerotic
      condition frequently accompanied by inflammation and oxidative stress. We
      hypothesized that vitamin C antioxidant levels might be low in PAD and are
      related to inflammation and disease severity. METHODS AND RESULTS: We
      investigated vitamin C (L-ascorbic acid) levels in 85 PAD patients, 106
      hypertensives without PAD, and 113 healthy subjects. Serum L-ascorbic acid
      concentrations were low among PAD patients (median, 27.8 micromol/L) despite
      comparable smoking status and dietary intake with the other groups (P<0.0001).
      Subclinical vitamin C deficiency (<11.4 micromol/L), confirmed by low serum
      alkaline phosphatase activity, was found in 14% of the PAD patients but not in
      the other groups. Serum C-reactive protein (CRP) concentrations were
      significantly higher in PAD patients (P<0.0001) and negatively correlated with L
      ascorbic acid levels (r=-0.742, P<0.0001). In stepwise multivariate analysis, low
      L-ascorbic acid concentration in PAD patients was associated with high CRP level
      (P=0.0001), smoking (P=0.0009), and shorter absolute claudication distance on a
      standardized graded treadmill test (P=0.029). CONCLUSIONS: Vitamin C
      concentrations are lower in intermittent claudicant patients in association with
      higher CRP levels and severity of PAD. Future studies attempting to relate
      vitamin C levels to disease occurrence should include in their analysis an
      inflammatory marker such as CRP.

PMID- 11294806
TI  - Myocardial blood flow and flow reserve after coronary reimplantation in patients
      after arterial switch and ross operation.
AB  - BACKGROUND: Coronary reimplantation is used in therapy for congenital heart
      disease, such as in the arterial switch (ASO) and Ross operations. The adequacy
      of myocardial perfusion may remain a matter of concern. The aim of the present
      study was to stratify the effect of coronary reimplantation on myocardial
      perfusion and to highlight the clinical relevance of any attenuation in
      myocardial perfusion. METHODS AND RESULTS: A total of 21 children with
      transposition of the great arteries at a mean interval of 11.2+/-2.9 years after
      ASO and 9 adolescents at a mean interval of 4.2+/-2.1 years after the Ross
      procedure were investigated. All patients were asymptomatic and had a normal
      exercise capacity. On stress echocardiography, 2 of the ASO patients had
      dyskinetic areas within the left ventricular myocardium, and 5 had adenosine
      induced perfusion defects on positron emission tomography. No coronary
      obstruction was detected on coronary angiography in any patient, but a common
      finding was right coronary dominance and a small caliber of the distal part of
      the left anterior descending artery. Coronary flow reserve (CFR) was
      significantly reduced in all patients after ASO when compared with 10 normal
      healthy volunteers (age, 25.6+/-5.3 years). CFR was normal in the 9 patients who
      had the Ross operation (age, 19.2+/-7.6 years); exercise-induced perfusion
      defects were not detected in the Ross patients. CONCLUSIONS: Children after ASO
      are asymptomatic, without clinical signs of coronary dysfunction. In contrast to
      patients who had the Ross operation, stress-induced perfusion defects and an
      attenuated CFR were documented. The prognostic implications of these findings and
      the clinical consequences are unclear; nevertheless, close clinical follow-up of
      ASO patients is mandatory.

PMID- 11294807
TI  - Myocardial efficiency and sympathetic reinnervation after orthotopic heart
      transplantation: a noninvasive study with positron emission tomography.
AB  - BACKGROUND: The lack of cardiac catecholamine uptake and storage caused by
      sympathetic denervation may influence performance of the transplanted heart.
      Reinnervation, occurring late after transplantation, may partially resolve these
      effects. In this study, oxidative metabolism and its relation to cardiac work
      were compared in allografts and normal and failing hearts, and the effects of
      sympathetic reinnervation were evaluated. METHODS AND RESULTS: Twenty-seven
      nonrejecting, symptom-free transplant recipients, 11 healthy control subjects,
      and 10 patients with severe dilated cardiomyopathy underwent PET with (11)C
      acetate for assessment of oxidative metabolism by the clearance constant k(mono)
      and radionuclide angiography or MRI for measurement of ventricular function,
      geometry, and work. Efficiency was estimated noninvasively by a work-metabolic
      index [WMI=(stroke volumexheart ratexsystolic pressure)/k(mono)]. In 14 of 27
      transplants, presence of regional reinnervation was identified with PET and the
      catecholamine analogue (11)C hydroxyephedrine (extent, 24+/-14% of left
      ventricle). The WMI was comparable in normal subjects and reinnervated and
      denervated transplants (6.2+/-2.3 versus 4.9+/-2.0 versus 4.9+/-1.2. 10(6) mm Hg.
      mL; P=NS) and significantly lower in cardiomyopathy patients (3.0+/-1.3. 10(6) mm
      Hg. mL; P<0.001). For normal subjects and transplant recipients, the WMI was
      significantly correlated with afterload (peripheral vascular resistance; r=-0.65,
      P<0.01), preload (end-diastolic volume; r=0.78, P<0.01), and stroke volume
      (r=0.81, P<0.01) but not with hydroxyephedrine retention (transplants only;
      r=0.09, P=NS). CONCLUSIONS: After transplantation, cardiac efficiency is improved
      compared with failing hearts and comparable to normal hearts. Differences between
      denervated and reinnervated allografts were not surveyed. Additionally, the
      dependency on loading conditions and contractility was preserved, suggesting that
      normal regulatory interactions for efficiency are intact and that sympathetic
      tone does not play a role under resting conditions.

PMID- 11294808
TI  - Increased vascular endothelial growth factor 165 binding to kinase insert domain
      containing receptor after infection of human endothelial cells by recombinant
      adenovirus encoding the Vegf(165) gene.
AB  - BACKGROUND: The angiogenic effect of vascular endothelial growth factor
      (VEGF(165)) is mediated mainly through the high-affinity tyrosine kinase receptor
      VEGF-R2 (KDR/flk-1). This study examined the effects of VEGF overexpression by
      primary human endothelial cells (ECs), which do not express VEGF under
      physiological conditions, on cell proliferation, VEGF binding to the kinase
      insert domain-containing receptor (KDR), and KDR expression. METHODS AND RESULTS:
      Human primary ECs and SMCs were infected by recombinant adenoviral vector
      encoding VEGF(165) (rAdVEGF). Proliferation rate, bromodeoxyuridine
      incorporation, (125)I-labeled VEGF(165) binding to the KDR receptor, and KDR
      expression were tested in the infected cells and in cells supplemented with VEGF
      protein. Enhanced proliferation and a significant increase in (125)I-VEGF(165)
      binding to the KDR receptor were induced by rAdVEGF infection of ECs (autocrine
      effect) as well as by addition of recombinant VEGF(165) to noninfected cells.
      Infection of ECs by rAdVEGF led to posttranscriptional upregulation of the KDR
      receptor, whereas KDR mRNA expression levels remained unchanged. Similar effects
      were observed with supplemented recombinant VEGF(165) to noninfected ECs;
      nevertheless, this phenomenon occurred only with high VEGF(165) concentrations
      (10 ng/mL). CONCLUSIONS: The effect of VEGF(165) on proliferation and
      upregulation of KDR receptor expression demonstrated an autocrine phenomenon of
      EC sensitization. The fact that high concentrations of VEGF may be achieved in
      vivo by local continuous overexpression of VEGF(165) by gene transfer emphasizes
      the potential advantage of gene transfer over protein supplementation for
      therapeutic angiogenesis.

PMID- 11294810
TI  - Effects of L-749,329, an ET(A)/ET(B) endothelin receptor antagonist, in a porcine
      coronary artery injury model of vascular restenosis.
AB  - BACKGROUND: Previous studies in animal models of angioplasty have suggested a
      role in neointimal hyperplasia for endothelins (ETs), potent vasoconstricting
      peptides that also exert growth-promoting effects. The present studies were
      undertaken to test the hypothesis that endothelin receptor blockade can reduce
      neointimal thickening in injured porcine coronary arteries. METHODS AND RESULTS:
      An ET(A)/ET(B) antagonist, L-749,329, was evaluated as an inhibitor of intimal
      thickening in a porcine balloon/stent model of coronary artery injury. L-749,329
      competitively inhibited [(125)I]ET-1 binding to porcine ET(A) (IC(50)
      approximately 0.3 nmol/L) or ET(B) (IC(50) approximately 20 nmol/L) receptors and
      inhibited ET-1-stimulated signaling in cell culture. In anesthetized pigs, big ET
      1-stimulated increases in systemic blood pressure were totally inhibited after
      intravenous infusion of L-749,329 (>/=0.2 mg. kg(-1). h(-1)). In vascular injury
      studies, pigs were treated with vehicle or L-749,329 (1 mg. kg(-1). h(-1))
      beginning 2 days before and continuing 28 days after experimental angioplasty.
      Left anterior descending, left circumflex, and/or right coronary arteries were
      injured by inflation of an angioplasty balloon wrapped with a coiled metallic
      stent. After 28 days, mean neointimal thickness in the L-749,329-treated group
      was reduced by 9.0% compared with vehicle-treated controls, but this effect was
      not statistically significant (P=0.13). CONCLUSIONS: Blockade of endothelin
      receptors for 28 days with only a mixed ET(A)/ET(B) receptor antagonist is
      insufficient to substantially inhibit intimal hyperplasia after balloon/stent
      coronary artery injury in the pig, in contrast to results with a selective ET(A)
      antagonist. The effects of selective or mixed ET(A)/ET(B) antagonists in diseased
      vessels remain to be determined in this model.

PMID- 11294809
TI  - Gene therapy with extracellular superoxide dismutase protects conscious rabbits
      against myocardial infarction.
AB  - BACKGROUND: Extracellular superoxide dismutase (Ec-SOD) may protect the heart
      against myocardial infarction (MI) because of its extended half-life and capacity
      to bind heparan sulfate proteoglycans on cellular surfaces. Accordingly, we used
      direct gene transfer to increase systemic levels of Ec-SOD and determined whether
      this gene therapy could protect against MI. METHODS AND RESULTS: The cDNA for
      human Ec-SOD was incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec
      SOD). Injection of this virus produced a high level of Ec-SOD in the liver, which
      was redistributed to the heart and other organs by injection of heparin.
      Untreated rabbits (group I) underwent a 30-minute coronary occlusion and 3 days
      of reperfusion. For comparison, preconditioned rabbits (group II) underwent a
      sequence of six 4-minute-occlusion/4-minute-reperfusion cycles 24 hours before
      the 30-minute occlusion. Control-treated rabbits (group III) were injected
      intravenously with Ad5/CMV/nls-LacZ, and gene-therapy rabbits (group IV) were
      injected with Ad5/CMV/Ec-SOD 3 days before the 30-minute occlusion. Both groups
      treated with Ad5 received intravenous heparin 2 hours before the 30-minute
      occlusion. Infarct size (percent risk area) was similar in groups I (57+/-6%) and
      III (58+/-5%). Ec-SOD gene therapy markedly reduced infarct size to 25+/-4%
      (P<0.01, group IV versus group III), a protection comparable to that of the late
      phase of ischemic preconditioning (29+/-3%, P<0.01 group II versus group I).
      CONCLUSIONS: Direct gene transfer of the cDNA encoding membrane-bound Ec-SOD
      affords powerful cardioprotection, providing proof of principle for the
      effectiveness of antioxidant gene therapy against MI.

PMID- 11294812
TI  - Late arterial responses (6 and 12 months) after (32)P beta-emitting stent
      placement: sustained intimal suppression with incomplete healing.
AB  - BACKGROUND: Three-month studies of stent-delivered brachytherapy in the rabbit
      model show reduced neointimal growth. However, intimal healing is delayed,
      raising the possibility that intimal inhibition is merely delayed rather than
      prevented. The purpose of this study was to explore the long-term histological
      changes after placement of beta-emitting radioactive stents in normal rabbit
      iliac arteries. METHODS AND RESULTS: Three-millimeter beta-emitting (32)P stents
      (6, 24, and 48 microCi) were placed in normal rabbit iliac arteries with
      nonradioactive stents as controls. Animals were euthanatized at 6 and 12 months,
      and histological assessment, morphometry, and analysis of endothelialization were
      performed. Morphometric measurements demonstrated a >50% reduction in intimal
      growth and percent lumen stenosis within 24- and 48-microCi stents versus control
      nonradioactive stents at both 6 and 12 months. However, the 24- and 48-microCi
      stents also showed delayed healing of the intimal surface, characterized by
      persistent fibrin thrombus with nonconfluent areas of matrix, incomplete
      endothelialization, and increased intimal cellular proliferation. Stent edge
      stenosis was present at 12 months in the 24- and 48-microCi stent groups,
      characterized by both intimal thickening and negative arterial remodeling.
      CONCLUSIONS: Inhibition of intimal growth is maintained 6 and 12 months after
      (32)P beta-emitting stent placement. However, delayed arterial healing,
      incomplete endothelialization, and edge effects are present.

PMID- 11294811
TI  - Selective alpha(v)beta(3)-receptor blockade reduces macrophage infiltration and
      restenosis after balloon angioplasty in the atherosclerotic rabbit.
AB  - BACKGROUND: alpha(v)beta(3)-Integrin receptors are upregulated in atherosclerotic
      arteries and play a key role in smooth muscle cell and possibly inflammatory cell
      migration. We hypothesized that after balloon angioplasty (BA) of atherosclerotic
      arteries, selective inhibition of the alpha(v)beta(3)-receptor by XT199, a small
      molecule, non-peptide-selective alpha(v)beta(3)-receptor antagonist, would reduce
      restenosis. METHODS AND RESULTS: After induction of focal atherosclerosis,
      rabbits underwent femoral BA and received XT199 (2.5 mg/kg IV bolus plus 2.5 mg.
      kg(-1). d(-1) IV; n=19) or vehicle (n=20) for 14 days. At 28 days after BA, the
      XT199 group had a larger lumen (0.75+/-0.26 versus 0.57+/-0.20 mm(2), P=0.03) and
      a smaller neointimal area (0.49+/-0.18 versus 0.68+/-0.25 mm(2), P=0.01) than the
      vehicle group. Angiographic analysis confirmed a 30% to 40% reduction in
      restenosis. Arteries harvested at 28 days after BA did not show a reduction in
      intima plus media smooth muscle cell content but did show a 50% reduction in
      macrophage cell density in the XT199 group (716+/-452 versus 1458+/-989
      cells/mm(2), P<0.006). Neovessel density at 28 days was also reduced (23+/-42
      versus 58+/-46 vessel cross sections/mm(2), P<0.02). Early after BA (ie, 3 to 7
      days), there was a decrease in intracellular adhesion molecule-1 and vascular
      cell adhesion molecule-1 expression, indicative of a reduction in vascular cell
      activation. CONCLUSIONS: Selective alpha(v)beta(3)-receptor blockade for 14 days
      after BA in the focally atherosclerotic rabbit significantly reduced restenosis
      and limited macrophage infiltration and neovascularization in the vessel wall.

PMID- 11294814
TI  - Migrating thrombus trapped in a patent foramen ovale.

PMID- 11294813
TI  - Cell therapy attenuates deleterious ventricular remodeling and improves cardiac
      performance after myocardial infarction.
AB  - BACKGROUND: Myocardial infarction (MI) promotes deleterious remodeling of the
      myocardium, resulting in ventricular dilation and pump dysfunction. We examined
      whether supplementing infarcted myocardium with skeletal myoblasts would (1)
      result in viable myoblast implants, (2) attenuate deleterious remodeling, and (3)
      enhance in vivo and ex vivo contractile performance. METHODS AND RESULTS:
      Experimental MI was induced by 1-hour coronary ligation followed by reperfusion
      in adult male Lewis rats. One week after MI, 10(6) myoblasts were injected
      directly into the infarct region. Three groups of animals were studied at 3 and 6
      weeks after cell therapy: noninfarcted control (control), MI plus sham injection
      (MI), and MI plus cell injection (MI+cell). In vivo cardiac function was assessed
      by maximum exercise capacity testing and ex vivo function was determined by
      pressure-volume curves obtained from isolated, red cell-perfused, balloon-in-left
      ventricle (LV) hearts. MI and MI+cell hearts had indistinguishable infarct sizes
      of approximately 30% of the LV. At 3 and 6 weeks after cell therapy, 92% (13 of
      14) of MI+cell hearts showed evidence of myoblast graft survival. MI+cell hearts
      exhibited attenuation of global ventricular dilation and reduced septum-to-free
      wall diameter compared with MI hearts not receiving cell therapy. Furthermore,
      cell therapy improved both post-MI in vivo exercise capacity and ex vivo LV
      systolic pressures. CONCLUSIONS: Implanted skeletal myoblasts form viable grafts
      in infarcted myocardium, resulting in enhanced post-MI exercise capacity and
      contractile function and attenuated ventricular dilation. These data illustrate
      that syngeneic myoblast implantation after MI improves both in vivo and ex vivo
      indexes of global ventricular dysfunction and deleterious remodeling and suggests
      that cellular implantation may be beneficial after MI.

PMID- 11294815
TI  - Magnetic resonance angiography of an aortic dissection.

PMID- 11294816
TI  - Implications of stroke risk criteria on the anticoagulation decision in
      nonvalvular atrial fibrillation.

PMID- 11294817
TI  - Edge restenosis after implantation of high activity (32)P radioactive beta
      emitting stents.

PMID- 11294818
TI  - Cross-talk between constitutive and inducible nitric oxide synthases.

PMID- 11294819
TI  - Defining diastolic heart failure.

PMID- 11294820
TI  - Clinical profile and outcome of idiopathic restrictive cardiomyopathy.

PMID- 11294821
TI  - 50th Annual scientific sessions of the American college of cardiology.

PMID- 11294822
TI  - Mitogen-activated protein (MAP) kinase pathways: regulation and physiological
      functions.
AB  - Mitogen-activated protein (MAP) kinases comprise a family of ubiquitous proline
      directed, protein-serine/threonine kinases, which participate in signal
      transduction pathways that control intracellular events including acute responses
      to hormones and major developmental changes in organisms. MAP kinases lie in
      protein kinase cascades. This review discusses the regulation and functions of
      mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions
      and findings from gene disruption studies are highlighted. Particular emphasis is
      on ERK1/2.

PMID- 11294823
TI  - The new human tissue kallikrein gene family: structure, function, and association
      to disease.
AB  - The human tissue kallikrein gene family was, until recently, thought to consist
      of only three genes. Two of these human kallikreins, prostate-specific antigen
      and human glandular kallikrein 2, are currently used as valuable biomarkers of
      prostatic carcinoma. More recently, new kallikrein-like genes have been
      discovered. It is now clear that the human tissue kallikrein gene family contains
      at least 15 genes. All genes share important similarities, including mapping at
      the same chromosomal locus (19q13.4), significant homology at both the nucleotide
      and protein level, and similar genomic organization. All genes encode for
      putative serine proteases and most of them are regulated by steroid hormones.
      Recent data suggest that at least a few of these kallikrein genes are connected
      to malignancy. In this review, we summarize the recently accumulated knowledge on
      the human tissue kallikrein gene family, including gene and protein structure,
      predicted enzymatic activities, tissue expression, hormonal regulation, and
      alternative splicing. We further describe the reported associations of the human
      kallikreins with various human diseases and identify future avenues for research.

PMID- 11294824
TI  - Alternative ribonucleic acid processing in endocrine systems.
AB  - Alternative RNA processing is a mechanism for creation of protein diversity
      through selective inclusion or exclusion of RNA sequence during
      posttranscriptional processing. More than one-third of human pre-mRNAs undergo
      alternative RNA processing modification, making this a ubiquitous biological
      process. The protein isoforms produced have distinct and sometimes opposite
      functions, underscoring the importance of this process. This review focuses on
      important endocrine genes regulated by alternative RNA processing. We discuss how
      diverse events such as spermatogenesis or GH action are regulated by this
      process. We focus on several endocrine (calcitonin/calcitonin gene-related
      peptide) and nonendocrine (Drosophila doublesex and P-element and mouse c-src)
      examples to highlight recent progress in the elucidation of molecular mechanisms
      regulating this process. Finally, we outline methods (model systems and
      techniques) used by investigators in this field to study processing of individual
      pre-mRNAS:

PMID- 11294825
TI  - Y chromosome microdeletions and alterations of spermatogenesis.
AB  - Three different spermatogenesis loci have been mapped on the Y chromosome and
      named "azoospermia factors" (AZFa, b, and c). Deletions in these regions remove
      one or more of the candidate genes (DAZ, RBMY, USP9Y, and DBY) and cause severe
      testiculopathy leading to male infertility. We have reviewed the literature and
      the most recent advances in Y chromosome mapping, focusing our attention on the
      correlation between Y chromosome microdeletions and alterations of
      spermatogenesis. More than 4,800 infertile patients were screened for Y
      microdeletions and published. Such deletions determine azoospermia more
      frequently than severe oligozoospermia and involve especially the AZFc region
      including the DAZ gene family. Overall, the prevalence of Y chromosome
      microdeletions is 4% in oligozoospermic patients, 14% in idiopathic severely
      oligozoospermic men, 11% in azoospermic men, and 18% in idiopathic azoospermic
      subjects. Patient selection criteria appear to substantially influence the
      prevalence of microdeletions. No clear correlation exists between the size and
      localization of the deletions and the testicular phenotype. However, it is clear
      that larger deletions are associated with the most severe testicular damage.
      Patients with Y chromosome deletions frequently have sperm either in the
      ejaculate or within the testis and are therefore suitable candidates for assisted
      reproduction techniques. This possibility raises a number of medical and ethical
      concerns, since the use of spermatozoa carrying Y chromosome deletions may
      produce pregnancies, but in such cases the genetic anomaly will invariably be
      passed on to male offspring.

PMID- 11294826
TI  - The effects of amiodarone on the thyroid.
AB  - Amiodarone is a benzofuranic-derivative iodine-rich drug widely used for the
      treatment of tachyarrhythmias and, to a lesser extent, of ischemic heart disease.
      It often causes changes in thyroid function tests (typically an increase in serum
      T(4) and rT(3), and a decrease in serum T(3), concentrations), mainly related to
      the inhibition of 5'-deiodinase activity, resulting in a decrease in the
      generation of T(3) from T(4) and a decrease in the clearance of rT(3). In 14-18%
      of amiodarone-treated patients, there is overt thyroid dysfunction, either
      amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism
      (AIH). Both AIT and AIH may develop either in apparently normal thyroid glands or
      in glands with preexisting, clinically silent abnormalities. Preexisting
      Hashimoto's thyroiditis is a definite risk factor for the occurrence of AIH. The
      pathogenesis of iodine-induced AIH is related to a failure to escape from the
      acute Wolff-Chaikoff effect due to defects in thyroid hormonogenesis, and, in
      patients with positive thyroid autoantibody tests, to concomitant Hashimoto's
      thyroiditis. AIT is primarily related to excess iodine-induced thyroid hormone
      synthesis in an abnormal thyroid gland (type I AIT) or to amiodarone-related
      destructive thyroiditis (type II AIT), but mixed forms frequently exist.
      Treatment of AIH consists of L-T(4) replacement while continuing amiodarone
      therapy; alternatively, if feasible, amiodarone can be discontinued, especially
      in the absence of thyroid abnormalities, and the natural course toward
      euthyroidism can be accelerated by a short course of potassium perchlorate
      treatment. In type I AIT the main medical treatment consists of the simultaneous
      administration of thionamides and potassium perchlorate, while in type II AIT,
      glucocorticoids are the most useful therapeutic option. Mixed forms are best
      treated with a combination of thionamides, potassium perchlorate, and
      glucocorticoids. Radioiodine therapy is usually not feasible due to the low
      thyroidal radioiodine uptake, while thyroidectomy can be performed in cases
      resistant to medical therapy, with a slightly increased surgical risk.

PMID- 11294827
TI  - Ovarian surface epithelium: biology, endocrinology, and pathology.
AB  - The epithelial ovarian carcinomas, which make up more than 85% of human ovarian
      cancer, arise in the ovarian surface epithelium (OSE). The etiology and early
      events in the progression of these carcinomas are among the least understood of
      all major human malignancies because there are no appropriate animal models, and
      because methods to culture OSE have become available only recently. The objective
      of this article is to review the cellular and molecular mechanisms that underlie
      the control of normal and neoplastic OSE cell growth, differentiation, and
      expression of indicators of neoplastic progression. We begin with a brief
      discussion of the development of OSE, from embryonic to the adult. The
      pathological and genetic changes of OSE during neoplastic progression are next
      summarized. The histological characteristics of OSE cells in culture are also
      described. Finally, the potential involvement of hormones, growth factors, and
      cytokines is discussed in terms of their contribution to our understanding of the
      physiology of normal OSE and ovarian cancer development.

PMID- 11294828
TI  - The primary structure of globin and linker chains from the chlorocruorin of the
      polychaete Sabella spallanzanii.
AB  - Annelid hemoglobins are organized in a very complex supramolecular network of
      interacting polypeptides, the structure of which is still not wholly resolved. We
      have separated by two-dimensional electrophoresis the 4-MDa chlorocruorin of
      Sabella spallanzanii and identified its components by amino-terminal sequencing.
      This work reveals a high rate of heterogeneity of constituent chains in a single
      animal as well as in the Sabella population. Using a cDNA library prepared from
      the hematopoietic tissue of this worm, we have isolated and fully sequenced most
      globin and linker cDNAs. The primary structure features of these polypeptides
      have been characterized by comparison with model globin and linker sequences.

PMID- 11294829
TI  - Dual level inhibition of E2F-1 activity by adeno-associated virus Rep78.
AB  - E2F-1, a major cellular transcription factor, plays a pivotal role in regulating
      the cell cycle. The activity of E2F-1 is negatively regulated by its interaction
      with retinoblastoma protein (pRB), and disruption of the pRB-E2F-1 complex, a
      hallmark of cellular transformation by DNA tumor viruses, leads to cell
      proliferation. Adeno-associated virus-2 (AAV) is known to have onco-suppressive
      properties against DNA tumor viruses. Here we provide, for the first time, the
      molecular basis for antioncogenic activity of AAV. Rep78, a major regulatory
      protein of AAV, interacts at the protein level with E2F-1 and stabilizes the pRB
      E2F-1 complex. At the DNA level, Rep78 binds to a putative site on the E2F-1
      promoter and down-regulates the adenovirus-induced E2F-1 transcription. This dual
      level of Rep78 activity leads to decreased cellular levels of free E2F-1, leading
      to its onco-suppressive properties.

PMID- 11294830
TI  - A new spectrin, beta IV, has a major truncated isoform that associates with
      promyelocytic leukemia protein nuclear bodies and the nuclear matrix.
AB  - We isolated cDNAs that encode a 77-kDa peptide similar to repeats 10-16 of beta
      spectrins. Its gene localizes to human chromosome 19q13.13-q13.2 and mouse
      chromosome 7, at 7.5 centimorgans. A 289-kDa isoform, similar to full-length beta
      spectrins, was partially assembled from sequences in the human genomic DNA data
      base and completely cloned and sequenced. RNA transcripts are seen predominantly
      in the brain, and Western analysis shows a major peptide that migrates as a 72
      kDa band. This new gene, spectrin betaIV, thus encodes a full-length minor
      isoform (SpbetaIVSigma1) and a truncated major isoform (SpbetaIVSigma5).
      Immunostaining of cells shows a micropunctate pattern in the cytoplasm and
      nucleus. In mesenchymal stem cells, the staining concentrates at nuclear dots
      that stain positively for the promyelocytic leukemia protein (PML). Expression of
      SpbetaIVSigma5 fused to green fluorescence protein in cells produces nuclear dots
      that include all PML bodies, which double in number in transfected cells.
      Deletion analysis shows that partial repeats 10 and 16 of SpbetaIVSigma5 are
      necessary for nuclear dot formation. Immunostaining of whole-mount nuclear
      matrices reveals diffuse positivity with accentuation at PML bodies. Spectrin
      betaIV is the first beta-spectrin associated with a subnuclear structure and may
      be part of a nuclear scaffold to which gene regulatory machinery binds.

PMID- 11294831
TI  - BENE, a novel raft-associated protein of the MAL proteolipid family, interacts
      with caveolin-1 in human endothelial-like ECV304 cells.
AB  - The MAL proteolipid, an integral protein present in glycolipid- and cholesterol
      enriched membrane (GEM) rafts, is an element of the machinery necessary for
      apical sorting in polarized epithelial Madin-Darby canine kidney cells. MAL was
      the first member identified of an extended family of proteins that have
      significant overall sequence identity. In this study we have used a newly
      generated monoclonal antibody to investigate an unedited member of this family,
      named BENE, which was found to be expressed in endothelial-like ECV304 cells and
      normal human endothelium. Human BENE was characterized as a proteolipid protein
      predominantly present in GEM rafts in ECV304 cells. Coimmunoprecipitation
      experiments revealed that BENE interacted with caveolin-1. Confocal
      immunofluorescence and electron microscopic analyses indicated that BENE mainly
      accumulated into intracellular vesicular/tubular structures that partially
      colocalize with internal caveolin-1. In response to cell surface cholesterol
      oxidation, BENE redistributed to the dilated vesicular structures that
      concentrate most of the caveolin-1 originally on the cell surface. After
      cessation of cholesterol oxidation, a detectable fraction of the BENE molecules
      migrated to the plasmalemma accompanying caveolin-1 and then returned
      progressively to its steady state distribution. Together, these features
      highlight the BENE proteolipid as being an element of the machinery for raft
      mediated trafficking in endothelial cells.

PMID- 11294832
TI  - Functional expression, characterization, and purification of the catalytic domain
      of human 11-beta -hydroxysteroid dehydrogenase type 1.
AB  - 11-beta-hydroxysteroid dehydrogenase type 1 catalyzes the conversion of cortisone
      to hormonally active cortisol and has been implicated in the pathogenesis of a
      number of disorders including insulin resistance and obesity. The enzyme is a
      glycosylated membrane-bound protein that has proved difficult to purify in an
      active state. Extracted enzyme typically loses the reductase properties seen in
      intact cells and shows principally dehydrogenase activity. The C-terminal
      catalytic domain is known to contain a disulfide bond and is located within the
      lumen of the endoplasmic reticulum, anchored to the membrane by a single N
      terminal transmembrane domain. We report here the functional expression of the
      catalytic domain of the human enzyme, without the transmembrane domain and the
      extreme N terminus, in Escherichia coli. Moderate levels of soluble active
      protein were obtained using an N-terminal fusion with thioredoxin and a 6xHis
      tag. In contrast, the inclusion of a 6xHis tag at the C terminus adversely
      affected protein solubility and activity. However, the highest levels of active
      protein were obtained using a construct expressing the untagged catalytic domain.
      Nonreducing electrophoresis revealed the presence of both monomeric and dimeric
      disulfide bonded forms; however, mutation of a nonconserved cysteine residue
      resulted in a recombinant protein with no intermolecular disulfide bonds but full
      enzymatic activity. Using the optimal combination of plasmid construct and E.
      coli host strain, the recombinant protein was purified to apparent homogeneity by
      single step affinity chromatography. The purified protein possessed both
      dehydrogenase and reductase activities with a K(m) of 1.4 micrometer for cortisol
      and 9.5 micrometer for cortisone. This study indicates that glycosylation, the N
      terminal region including the transmembrane helix, and intermolecular disulfide
      bonds are not essential for enzyme activity and that expression in bacteria can
      provide active recombinant protein for future structural and functional studies.

PMID- 11294833
TI  - Expression, activity, and subcellular localization of the Yin Yang 1
      transcription factor in Xenopus oocytes and embryos.
AB  - Yin Yang 1 (YY1) is a multifunctional transcription factor that acts as an
      activator, repressor, or initiator of transcription of numerous cellular and
      viral genes. Previous studies in tissue culture model systems suggest YY1 plays a
      role in development and differentiation in multiple cell types, but the
      biological role of YY1 in vertebrate oocytes and embryos is not well understood.
      Here we analyzed expression, activity, and subcellular localization profiles of
      YY1 during Xenopus laevis development. Abundant levels of YY1 mRNA and protein
      were detected in early stage oocytes and in all subsequent stages of oocyte and
      embryonic development through to swimming larval stages. The DNA binding activity
      of YY1 was detected only in early oocytes (stages I and II) and in embryos after
      the midblastula transition (MBT), which suggested that its potential to modulate
      gene expression may be specifically repressed in the intervening period of
      development. Experiments to determine transcriptional activity showed that
      addition of YY1 recognition sites upstream of the thymidine kinase promoter had
      no stimulatory or repressive effect on basal transcription in oocytes and post
      MBT embryos. Although the apparent transcriptional inactivity of YY1 in oocytes
      could be explained by the absence of DNA binding activity at this stage of
      development, the lack of transcriptional activity in post-MBT embryos was not
      expected given the ability of YY1 to bind its recognition elements. Subsequent
      Western blot and immunocytochemical analyses showed that YY1 is localized in the
      cytoplasm in oocytes and in cells of developing embryos well past the MBT. These
      findings suggest a novel mode of YY1 regulation during early development in which
      the potential transcriptional function of the maternally expressed factor is
      repressed by cytoplasmic localization.

PMID- 11294834
TI  - The absence of oligonucleosomal DNA fragmentation during apoptosis of IMR-5
      neuroblastoma cells: disappearance of the caspase-activated DNase.
AB  - Caspase-activated DNase is responsible for the oligonucleosomal DNA degradation
      during apoptosis. DNA degradation is thought to be important for multicellular
      organisms to prevent oncogenic transformation or as a mechanism of viral defense.
      It has been reported that certain cells, including some neuroblastoma cell lines
      such as IMR-5, enter apoptosis without digesting DNA in such a way. We have
      analyzed the causes for the absence of DNA laddering in staurosporine-treated IMR
      5 cells, and we have found that most of the molecular mechanisms controlling
      apoptosis are well preserved in this cell line. These include degradation of
      substrates for caspases, blockade of cell death by antiapoptotic genes such as
      Bcl-2 or Bcl-X(L), or normal levels and adequate activation of caspase-3.
      Moreover, these cells display normal levels of caspase-activated DNase and its
      inhibitory protein, inhibitor of caspase-activated DNase, and their cDNA
      sequences are identical to those reported previously. Nevertheless, IMR-5 cells
      lose caspase-activated DNase during apoptosis and recover their ability to
      degrade DNA when human recombinant caspase-activated DNase is overexpressed. Our
      results lead to the conclusion that caspase-activated DNase is processed during
      apoptosis of IMR-5 cells, making these cells a good model to study the relevance
      of this endonuclease in physiological or pathological conditions.

PMID- 11294835
TI  - The evolution of extracellular hemoglobins of annelids, vestimentiferans, and
      pogonophorans.
AB  - The evolution of extracellular hemoglobins of annelids, vestimentiferans, and
      pogonophorans was investigated by applying cladistic and distance-based
      approaches to reconstruct the phylogenetic relationships of this group of
      respiratory pigments. We performed this study using the aligned sequences of
      globin and linker chains that are the constituents of these complex molecules.
      Three novel globin and two novel linker chains of Sabella spallanzanii described
      in an accompanying paper (Pallavicini, A., Negrisolo, E., Barbato, R., Dewilde,
      S., Ghiretti-Magaldi, A., Moens, L., and Lanfranchi, G. (2001) J. Biol. Chem.
      276, 26384--26390) were also included. Our results allowed us to test previous
      hypotheses on the evolutionary pathways of these proteins and to formulate a new
      most parsimonious model of molecular evolution. According to this novel model,
      the genes coding for the polypeptides forming these composite molecules were
      already present in the common ancestor of annelids, vestimentiferans, and
      pogonophorans.

PMID- 11294836
TI  - Transcriptional activation by a matrix associating region-binding protein.
      contextual requirements for the function of bright.
AB  - Bright (B cell regulator of IgH transcription) is a B cell-specific, matrix
      associating region-binding protein that transactivates gene expression from the
      IgH intronic enhancer (E mu). We show here that Bright has multiple contextual
      requirements to function as a transcriptional activator. Bright cannot
      transactivate via out of context, concatenated binding sites. Transactivation is
      maximal on integrated substrates. Two of the three previously identified binding
      sites in E mu are required for full Bright transactivation. The Bright DNA
      binding domain defined a new family, which includes SWI1, a component of the
      SWI.SNF complex shown to have high mobility group-like DNA binding
      characteristics. Similar to one group of high mobility group box proteins, Bright
      distorts E mu binding site-containing DNA on binding, supporting the concept that
      it mediates E mu remodeling. Transfection studies further implicate Bright in
      facilitating spatially separated promoter-enhancer interactions in both transient
      and stable assays. Finally, we show that overexpression of Bright leads to
      enhanced DNase I sensitivity of the endogenous E mu matrix associating regions.
      These data further suggest that Bright may contribute to increased gene
      expression by remodeling the immunoglobulin locus during B cell development.

PMID- 11294837
TI  - Monoglucosylated oligomannosides are released during the degradation process of
      newly synthesized glycoproteins.
AB  - The Chinese hamster ovary mutant MI8-5 is known to synthesize Man(9)GlcNAc(2)-P-P
      dolichol rather than the fully glucosylated lipid intermediate
      Glc(3)Man(9)GlcNAc(2)-P-P-dolichol. This nonglucosylated oligosaccharide lipid
      precursor is used as donor for N-glycosylation. In this paper we demonstrate that
      a significant part of the glycans bound to the newly synthesized glycoproteins in
      MI8-5 cells are monoglucosylated. The presence of monoglucosylated glycans on
      glycoproteins determines their binding to calnexin as part of the quality control
      machinery. Furthermore, we point out the presence of Glc(1)Man(5)GlcNAc(1) in the
      cytosol of MI8-5 cells. This indicates that part of the monoglucosylated
      glycoproteins can be directed toward a deglycosylation process that occurs in the
      cytosol. Besides studies on glycoprotein degradation based on the disappearance
      of protein moieties, MI8-5 cells can be used as a tool to elucidate the various
      step leading to glycoprotein degradation by studying the fate of the glycan
      moieties.

PMID- 11294838
TI  - Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the
      SHP-1 protein-tyrosine phosphatase.
AB  - The protein-tyrosine phosphatase SHP-1 has been shown to be a negative regulator
      of multiple signaling pathways in hematopoietic cells. In this study, we
      demonstrate that SHP-1 dephosphorylates the lymphoid-specific Src family kinase
      Lck at Tyr-394 when both are transiently co-expressed in nonlymphoid cells. We
      also demonstrate that a GST-SHP-1 fusion protein specifically dephosphorylates
      Lck at Tyr-394 in vitro. Because phosphorylation of Tyr-394 activates Lck, the
      fact that SHP-1 specifically dephosphorylates this site suggests that SHP-1 is a
      negative regulator of Lck. The failure of SHP-1 to inactivate Lck may contribute
      to some of the lymphoid abnormalities observed in motheaten mice.

PMID- 11294839
TI  - Actin filament cross-linking by MARCKS: characterization of two actin-binding
      sites within the phosphorylation site domain.
AB  - We recently identified conformational changes that occur upon phosphorylation of
      myristoylated alanine-rich protein kinase C substrate (MARCKS) that preclude
      efficient cross-linking of actin filaments (Bubb, M. R., Lenox, R. H., and
      Edison, A. S. (1999) J. Biol. Chem. 274, 36472-36478). These results implied that
      the phosphorylation site domain of MARCKS has two actin-binding sites. We now
      present evidence for the existence of two actin-binding sites that not only
      mutually compete but also specifically compete with the actin-binding proteins
      thymosin beta(4) and actobindin to bind to actin. The effects of substitution of
      alanine for phenylalanine within a repeated hexapeptide segment suggest that the
      noncharged region of the domain contributes to binding affinity, but the binding
      affinity of peptides corresponding to each binding site has a steep dependence on
      salt concentration, consistent with presumed electrostatic interactions between
      these polycationic peptides and the polyanionic N terminus of actin.
      Phosphorylation decreases the site-specific affinity by no more than 0.7
      kcal/mol, which is less than the effect of alanine substitution. However,
      phosphorylation has a much greater effect than alanine substitution on the loss
      of actin filament cross-linking activity. These results are consistent with the
      hypothesis that the compact structure resulting from conformational changes due
      to phosphorylation, in addition to modest decreases in site-specific affinity,
      explains the loss of cross-linking activity in phosphorylated MARCKS.

PMID- 11294840
TI  - Novel Sp family-like transcription factors are present in adult insect cells and
      are involved in transcription from the polyhedrin gene initiator promoter.
AB  - We earlier documented the involvement of a cellular factor, polyhedrin (polh)
      promoter-binding protein, in transcription from the Autographa californica
      nuclear polyhedrosis virus polh gene promoter. Sequences upstream of the polh
      promoter were found to influence polh promoter-driven transcription. Analysis of
      one such region, which could partially compensate for the mutated polh promoter
      and also activate transcription from the wild-type promoter, revealed a sequence
      (AcSp) containing a CACCC motif and a loose GC box resembling the binding motifs
      of the transcription factor Sp1. AcSp and the consensus Sp1 sequence (cSp)
      specifically bound factor(s) in HeLa and Spodoptera frugiperda (Sf9) insect cell
      nuclear extracts to generate identical binding patterns, indicating the similar
      nature of the factor(s) interacting with these sequences. The AcSp and cSp
      oligonucleotides enhanced in vivo expression of a polh promoter-driven luciferase
      gene. In vivo mopping of these factor(s) significantly reduced transcription from
      the polh promoter. Recombinant viruses carrying deletions in the upstream AcSp
      sequence confirmed the requirement of these factor(s) in polh promoter-driven
      transcription in the viral context. We demonstrate for the first time DNA-protein
      interactions involving novel members of the Sp family of proteins in adult insect
      cells and their involvement in transcription from the polh promoter.

PMID- 11294841
TI  - Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like
      factor-1 composite cytokine: specific requirement of the membrane-bound form of
      ciliary neurotrophic factor receptor alpha component.
AB  - Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation
      and survival of a number of neural cell types. Its receptor complex consists of a
      ligand-binding component, CNTF receptor (CNTFR), associated with two signaling
      receptor components, gp130 and leukemia inhibitory factor receptor (LIFR).
      Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest
      that CNTFR serves as a receptor for a second developmentally important ligand. We
      recently demonstrated that cardiotrophin-like cytokine (CLC) associates with the
      soluble orphan receptor cytokine-like factor-1 (CLF) to form a heterodimeric
      cytokine that displayed activities only on cells expressing the tripartite CNTF
      receptor on their surface. In this present study we examined the membrane binding
      of the CLC/CLF composite cytokine and observed a preferential interaction of the
      cytokine with the CNTFR subunit. Signaling pathways recruited by the CLC/CLF
      complex in human neuroblastoma cell lines were also analyzed in detail. The
      results obtained showed an activation of Janus kinases (JAK1, JAK2, and TYK2)
      leading to a tyrosine phosphorylation of the gp130 and LIFR. The phosphorylated
      signaling receptors served in turn as docking proteins for signal transducing
      molecules such as STAT3 and SHP-2. In vitro analysis revealed that the gp130-LIFR
      pathway could also stimulate the phosphatidylinositol 3-kinase and the mitogen
      activated protein kinase pathways. In contrast to that reported before for CNTF,
      soluble CNTFR failed to promote the action CLC/CLF, and an absolute requirement
      of the membrane form of CNTFR was required to generate a functional response to
      the composite cytokine. This study reinforces the functional similarity between
      CNTF and the CLC/CLF composite cytokine defining the second ligand for CNTFR.

PMID- 11294842
TI  - Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role
      of o-glycans in conferring protease resistance.
AB  - Apolipoprotein(a) (apo(a)) is a multikringle domain glycoprotein that exists
      covalently linked to apolipoprotein B100 of low density lipoprotein, to form the
      lipoprotein(a) (Lp(a)) particle, or as proteolytic fragments. Elevated plasma
      concentrations of apo(a) and its fragments may promote atherosclerosis, but the
      underlying mechanisms are incompletely understood. The factors influencing apo(a)
      proteolysis are also uncertain. Here we have used exoglycosidase digestion and
      mass spectrometry to sequence the Asn (N)-linked and Ser/Thr (O)-linked
      oligosaccharides of human apo(a). We also assessed the potential role of apo(a) O
      glycans in protecting thermolysin-sensitive regions of the polypeptide. Apo(a)
      contained two major N-glycans that accounted for 17% of the total oligosaccharide
      structures. The N-glycans were complex biantennary structures present in either a
      mono- or disialylated state. The O-glycans were mostly (80%) represented by the
      monosialylated core type 1 structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with
      smaller amounts of disialylated and non-sialylated O-glycans also detected.
      Removal of apo(a) O-glycans by sialidase and O-glycosidase treatment dramatically
      increased the sensitivity of the polypeptide to thermolysin digestion. These
      studies provide the first direct sequencing data for apo(a) glycans and indicate
      a novel function for apo(a) O-glycans that is potentially related to the
      atherogenicity of Lp(a).

PMID- 11294843
TI  - Aromatic amino acids are critical for stability of the bicoid homeodomain.
AB  - The Drosophila Bicoid (Bcd) protein plays a dual role as a transcription and
      translation factor dependent on the unique DNA and RNA binding properties of the
      homeodomain (HD). We have used circular dichroism and fluorescence spectroscopy
      to probe the structure and stability of the Bcd-HD, for which a high resolution
      structure is not yet available. The fluorescence from the single tryptophan
      residue in the HD (Trp-48) is strongly quenched in the native state but is
      dramatically enhanced ( approximately 20-fold) upon denaturation. Similar results
      were obtained with the Ultrabithorax HD (Ubx-HD), suggesting that the unusual
      tryptophan fluorescence may be a general phenomenon of HD proteins. We have used
      site-directed mutagenesis to explore the role of aromatic acids in the structure
      of the Bcd-HD and to evaluate the proposal that interactions between the strictly
      conserved Trp residue in HDs and nearby aromatic residues are responsible for the
      fluorescence quenching in the native state. We determined that both Trp-48 and
      Phe-8 in the N-terminal region of the HD are individually necessary for
      structural stability of the Bcd-HD, the latter most likely as a factor
      coordinating the orientation of the N-terminal helix I and the recognition helix
      for efficient binding to a DNA target.

PMID- 11294844
TI  - Sequence properties of the 1,2-diacylglycerol 3-glucosyltransferase from
      Acholeplasma laidlawii membranes. Recognition of a large group of lipid
      glycosyltransferases in eubacteria and archaea.
AB  - Synthesis of the nonbilayer-prone alpha-monoglucosyldiacylglycerol (MGlcDAG) is
      crucial for bilayer packing properties and the lipid surface charge density in
      the membrane of Acholeplasma laidlawii. The gene for the responsible, membrane
      bound glucosyltransferase (alMGS) (EC ) was sequenced and functionally cloned in
      Escherichia coli, yielding MGlcDAG in the recombinants. Similar amino acid
      sequences were encoded in the genomes of several Gram-positive bacteria
      (especially pathogens), thermophiles, archaea, and a few eukaryotes. All of these
      contained the typical EX(7)E catalytic motif of the CAZy family 4 of alpha
      glycosyltransferases. The synthesis of MGlcDAG by a close sequence analog from
      Streptococcus pneumoniae (spMGS) was verified by polymerase chain reaction
      cloning, corroborating a connection between sequence and functional similarity
      for these proteins. However, alMGS and spMGS varied in dependence on anionic
      phospholipid activators phosphatidylglycerol and cardiolipin, suggesting certain
      regulatory differences. Fold predictions strongly indicated a similarity for
      alMGS (and spMGS) with the two-domain structure of the E. coli MurG cell envelope
      glycosyltransferase and several amphipathic membrane-binding segments in various
      proteins. On the basis of this structure, the alMGS sequence charge distribution,
      and anionic phospholipid dependence, a model for the bilayer surface binding and
      activity is proposed for this regulatory enzyme.

PMID- 11294845
TI  - Alternative splicing in the ligand binding domain of mouse ApoE receptor-2
      produces receptor variants binding reelin but not alpha 2-macroglobulin.
AB  - LR7/8B and ApoER2 are recently discovered members of the low density lipoprotein
      (LDL) receptor family. Although structurally different, these two proteins are
      derived from homologous genes in chicken and man by alternative splicing and
      contain 7 or 8 LDL receptor ligand-binding repeats. Here we present the cDNA for
      ApoER2 cloned from mouse brain and describe splice variants in the ligand binding
      domain of this protein, which are distinct from those present in man and chicken.
      The cloned cDNA is coding for a receptor with only five LDL receptor ligand
      binding repeats, i.e. comprising repeats 1-3, 7, and 8. Reverse transcriptase
      polymerase chain reaction analysis of mRNA from murine brain revealed the
      existence of two additional transcripts. One is lacking repeat 8, and in the
      other repeat 8 is substituted for by a 13-amino acid insertion with a consensus
      site for furin cleavage arising from an additional small exon present in the
      murine gene. None of the transcripts in the mouse, however, contain repeats 4-6.
      In murine placenta only the form containing repeats 1-3 and 7 and the furin
      cleavage site is detectable. Analysis of the corresponding region of the murine
      gene showed the existence of 6 exons coding for a total of 8 ligand binding
      repeats, with one exon encoding repeats 4-6. Exon trapping experiments
      demonstrated that this exon is constitutively spliced out in all murine
      transcripts. Thus, the murine ApoER2 gene codes for receptor variants harboring
      either 4 or 5 binding repeats only. Recombinant expression of the 5-repeat and 4
      repeat variants showed that repeats 1-3, 7, and 8 are sufficient for binding of
      beta-very low density lipoprotein and reelin, but not for recognition of alpha(2)
      macroglobulin, which binds to the avian homologue of ApoER2 harboring 8 ligand
      binding repeats.

PMID- 11294846
TI  - The 3'-untranslated region of murine cyclooxygenase-2 contains multiple
      regulatory elements that alter message stability and translational efficiency.
AB  - Renal mesangial cells regulate their expression of the pro-inflammatory gene
      cyclooxygenase-2 (COX-2) through mechanisms involving gene transcription and post
      transcriptional events. Post-transcriptional regulation of COX-2 is dependent, in
      part, on sequences within the 3'-untranslated region (3'-UTR) of the COX-2 mRNA.
      Insertion of the entire 3'-UTR of COX-2 into the 3'-UTR of luciferase resulted in
      a 70% decrease in luciferase enzymatic activity. Measurement of steady-state
      reporter gene mRNA levels suggested that the loss of activity was due to
      decreased translational efficiency. Deletion analysis identified the first 60
      nucleotides of the 3'-UTR of COX-2 as a major translational control element. This
      region of the 3'-UTR of COX-2 is highly conserved across species; is AU-rich; and
      contains multiple repeats of the regulatory sequence AUUUA, reported to confer
      post-transcriptional control. In addition, we identified regions of the 3'-UTR of
      COX-2 outside of the first 60 nucleotides that altered message stability. Some of
      these regions contained AUUUA consensus sequences, whereas others did not, and
      represent novel control elements. These results suggest that expression of COX-2
      in mesangial cells depends on the complex integration of multiple signals derived
      from the 3'-UTR of the message.

PMID- 11294847
TI  - Structural and regulatory properties of pyruvate kinase from the Cyanobacterium
      synechococcus PCC 6301.
AB  - Pyruvate kinase (PK) from the cyanobacterium Synechococcus PCC 6301 was purified
      1,300-fold to electrophoretic homogeneity and a final specific activity of 222
      micromol of pyruvate produced/min/mg of protein. The enzyme was shown to have a
      pI of 5.7 and to exist as a 280-kDa homotetramer composed of 66-kDa subunits.
      This PK appears to be immunologically related to Bacillus PK and a green algal
      chloroplast PK, but not to rabbit muscle PK, or vascular plant cytosolic and
      plastidic PKs. The N-terminal amino acid sequence of the Synechococcus PK
      exhibited maximal (67%) identity with the corresponding region of a putative PK-A
      sequence deduced from the genome of the cyanobacterium, Synechocystis PCC 6803.
      Synechococcus PK was relatively heat-labile and displayed a broad pH optimum
      around pH 7.0. Its activity was not influenced by K(+), but required high
      concentrations of Mg(2+), and was relatively nonspecific with respect to the
      nucleoside diphosphate substrate. Potent allosteric regulation by various
      effectors was observed (activators: hexose monophosphates, ribose 5-phosphate,
      glycerol 3-phosphate, and AMP; inhibitors: fructose 1,6-bisphosphate, inorganic
      phosphate, ATP, and several Krebs' cycle intermediates). The enzyme exhibited
      marked positive cooperativity for phosphoenolpyruvate, which was eliminated or
      reduced by the presence of the allosteric activators. The results are discussed
      in terms of the phylogeny and probable central role of PK in the control of
      cyanobacterial glycolysis.

PMID- 11294848
TI  - Structure and mechanism of action of an indolicidin peptide derivative with
      improved activity against gram-positive bacteria.
AB  - Indolicidin, an antimicrobial peptide with a unique amino acid sequence
      (ILPWKWPWWPWRR-NH(2)) is found in bovine neutrophils. A derivative of
      indolicidin, CP10A, has alanine residues substituted for proline residues and has
      improved activity against Gram-positive organisms. Transmission electron
      microscopy of Staphylococcus aureus and Staphylococcus epidermidis treated with
      CP10A showed mesosome-like structures in the cytoplasm. The peptide at 2-fold the
      minimal inhibitory concentration did not show significant killing of S. aureus
      ISP67 (a histidine, uridine, and thymidine auxotroph) but did show an early
      effect on histidine and uridine incorporation and, later, an effect on thymidine
      incorporation. Upon interaction with liposomes, detergents, and lipoteichoic
      acid, CP10A was shown by circular dichroism spectroscopy to undergo a change in
      secondary structure. Fluorescence spectroscopy indicated that the tryptophan
      residues were located at the hydrophobic/hydrophilic interface of liposomes and
      detergent micelles and were inaccessible to the aqueous quencher KI. The three
      dimensional structure of CP10A in the lipid mimetic dodecylphosphocholine was
      determined using two-dimensional NMR methods and was characterized as a short,
      amphipathic helical structure, whereas indolicidin was previously shown to have
      an extended structure. These studies have introduced a cationic peptide with a
      unique structure and an ability to interact with membranes and to affect
      intracellular synthesis of proteins, RNA, and DNA.

PMID- 11294849
TI  - Molecular basis for the susceptibility of fibrin-bound thrombin to inactivation
      by heparin cofactor ii in the presence of dermatan sulfate but not heparin.
AB  - Although fibrin-bound thrombin is resistant to inactivation by
      heparin.antithrombin and heparin.heparin cofactor II complexes, indirect studies
      in plasma systems suggest that the dermatan sulfate.heparin cofactor II complex
      can inhibit fibrin-bound thrombin. Herein we demonstrate that fibrin monomer
      produces a 240-fold decrease in the heparin-catalyzed rate of thrombin inhibition
      by heparin cofactor II but reduces the dermatan sulfate-catalyzed rate only 3
      fold. The protection of fibrin-bound thrombin from inhibition by heparin.heparin
      cofactor II reflects heparin-mediated bridging of thrombin to fibrin that results
      in the formation of a ternary heparin.thrombin.fibrin complex. This complex,
      formed as a result of three binary interactions (thrombin.fibrin,
      thrombin.heparin, and heparin.fibrin), limits accessibility of heparin-catalyzed
      inhibitors to thrombin and induces conformational changes at the active site of
      the enzyme. In contrast, dermatan sulfate binds to thrombin but does not bind to
      fibrin. Although a ternary dermatan sulfate. thrombin.fibrin complex forms,
      without dermatan sulfate-mediated bridging of thrombin to fibrin, only two binary
      interactions exist (thrombin.fibrin and thrombin. dermatan sulfate).
      Consequently, thrombin remains susceptible to inactivation by heparin cofactor
      II. This study explains why fibrin-bound thrombin is susceptible to inactivation
      by heparin cofactor II in the presence of dermatan sulfate but not heparin.

PMID- 11294850
TI  - The matricellular protein SPARC/osteonectin as a newly identified factor up
      regulated in obesity.
AB  - Alterations in the expression level of genes may contribute to the development
      and pathophysiology of obesity. To find genes differentially expressed in adipose
      tissue during obesity, we performed suppression subtractive hybridization on
      epididymal fat mRNA from goldthioglucose (GTG) obese mice and from their lean
      littermates. We identified the secreted protein acidic and rich in cysteine
      (SPARC), a protein that mediates cell-matrix interactions and plays a role in
      modulation of cell adhesion, differentiation, and angiogenesis. SPARC mRNA
      expression in adipose tissue was markedly increased (between 3- and 6-fold) in
      three different models of obesity, i.e. GTG mice, ob/ob mice, and AKR mice, after
      6 weeks of a high fat diet. Immunoblotting of adipocyte extracts revealed a
      similar increase in protein level. Using a SPARC-specific ELISA, we demonstrated
      that SPARC is secreted by isolated adipocytes. We found that insulin
      administration to mice increased SPARC mRNA in the adipose tissue. Food
      deprivation had no effect on SPARC expression, but after high fat refeeding SPARC
      mRNA levels were significantly increased. Our results reveal both hormonal and
      nutritional regulation of SPARC expression in the adipocyte, and importantly, its
      alteration in obesity. Finally, we show that purified SPARC increased mRNA levels
      of plasminogen activator inhibitor 1 (PAI-1) in cultured rat adipose tissue
      suggesting that elevated adipocyte expression of SPARC might contribute to the
      abnormal expression of PAI-1 observed in obesity. We propose that SPARC is a
      newly identified autocrine/paracrine factor that could affect key functions in
      adipose tissue physiology and pathology.

PMID- 11294851
TI  - Mechanism of the formation and proteolytic release of H2O2-induced dityrosine and
      tyrosine oxidation products in hemoglobin and red blood cells.
AB  - Oxyhemoglobin exposed to a continuous flux of H(2)O(2) underwent oxidative
      modifications, including limited release of fluorescent fragmentation products.
      The main fragments formed were identified as oxidation products of tyrosine,
      including dopamine, dopamine quinone, and dihydroxyindol. Further release of
      these oxidation products plus dityrosine was only seen after proteolytic
      degradation of the oxidatively modified hemoprotein. A possible mechanism is
      proposed to explain the formation of these oxidation products that includes
      cyclization, decarboxylation, and further oxidation of the intermediates. Release
      of dityrosine is proposed as a useful technique for evaluating selective
      proteolysis after an oxidative stress, because dityrosine is metabolically
      stable, and it is only released after enzymatic hydrolysis of the oxidatively
      modified protein. The measurement can be accomplished by high performance liquid
      chromatography with fluorescence detection or by high efficiency thin layer
      chromatography. Comparable results, in terms of dityrosine release, were obtained
      using red blood cells of different sources after exposing them to a flux of
      H(2)O(2). Furthermore, dityrosine has been reported to occur in a wide variety of
      oxidatively modified proteins. These observations suggest that dityrosine
      formation and release can be used as a highly specific marker for protein
      oxidation and selective proteolysis.

PMID- 11294852
TI  - Cloning and characterization of the 5'-flanking region of the human transcription
      factor Sp1 gene.
AB  - The 5'-flanking region of the human Sp1 gene was cloned and characterized.
      Sequence analysis of this region showed the absence of both CAAT and TATA boxes
      and an initiator element. The proximal promoter of the Sp1 gene is a GC-rich
      region that contains multiple GC boxes and Ap2 binding sites. The major
      transcription start site is located 63 base pairs upstream of the translation
      start site. Transfection experiments demonstrate that all the elements necessary
      to achieve significant basal transcription activity are located between positions
      -443 and -20 relative to the translational start. Sp1 and Sp3 proteins bind to
      the downstream GC box located in the proximal promoter of Sp1. Furthermore, we
      demonstrate that the Sp1 protein activates Sp1 transcription activity; thus the
      Sp1 gene is autoregulated.

PMID- 11294853
TI  - Physical properties of erythrocyte ghosts that determine susceptibility to
      secretory phospholipase A2.
AB  - Artificial membranes may be resistant or susceptible to catalytic attack by
      secretory phospholipase A(2) (sPLA(2)) depending on the physical properties of
      the membrane. Living cells are normally resistant but become susceptible during
      trauma, apoptosis, and/or a significant elevation of intracellular calcium.
      Intact erythrocytes and ghosts were studied to determine whether the principles
      learned from artificial systems apply to biological membranes. Membrane
      properties such as phospholipid and/or protein composition, morphology, and
      microscopic characteristics (e.g. fluidity) were manipulated by preparing ghosts
      under different experimental conditions such as in the presence or absence of
      divalent cations with or without ATP. The properties of each membrane preparation
      were assessed by biochemical and physical means (fluorescence spectroscopy and
      electron and two-photon microscopy using the membrane probes bis-pyrene and
      laurdan) and compared with sPLA(2) activity. The properties that appeared most
      relevant were the degree of phosphatidylserine exposure on the outer face of the
      membrane and changes to the membrane physical state detected by bis-pyrene and
      laurdan. Specifically, vulnerability to hydrolysis by sPLA(2) was associated with
      an increase in bilayer order apparently reflective of expansion of membrane
      regions of diminished fluidity. These results argue that the general principles
      identified from studies with artificial membranes apply to biological systems.

PMID- 11294854
TI  - Mechanisms by which intracellular calcium induces susceptibility to secretory
      phospholipase A2 in human erythrocytes.
AB  - Exposure of human erythrocytes to the calcium ionophore ionomycin rendered them
      susceptible to the action of secretory phospholipase A(2) (sPLA(2)). Analysis of
      erythrocyte phospholipid metabolism by thin-layer chromatography revealed
      significant hydrolysis of both phosphatidylcholine and phosphatidylethanolamine
      during incubation with ionomycin and sPLA(2). Several possible mechanisms for the
      effect of ionomycin were considered. Involvement of intracellular phospholipases
      A(2) was excluded since inhibitors of these enzymes had no effect. Assessment of
      membrane oxidation by cis-parinaric acid fluorescence and comparison to the
      oxidants diamide and phenylhydrazine revealed that oxidation does not participate
      in the effect of ionomycin. Incubation with ionomycin caused classical physical
      changes to the erythrocyte membrane such as morphological alterations
      (spherocytosis), translocation of aminophospholipids to the outer leaflet of the
      membrane, and release of microvesicles. Experiments with phenylhydrazine, KCl,
      quinine, merocyanine 540, the calpain inhibitor E-64d, and the scramblase
      inhibitor R5421 revealed that neither phospholipid translocation nor vesicle
      release was required to induce susceptibility. Results from fluorescence
      spectroscopy and two-photon excitation scanning microscopy using the membrane
      probe laurdan argued that susceptibility to sPLA(2) is a consequence of increased
      order of membrane lipids.

PMID- 11294855
TI  - Photoinhibition of Chlamydomonas reinhardtii in State 1 and State 2: damages to
      the photosynthetic apparatus under linear and cyclic electron flow.
AB  - The relationship between state transitions and photoinhibition has been studied
      in Chlamydomonas reinhardtii cells. In State 2, photosystem II activity was more
      inhibited by light than in State 1. In State 2, however, the D1 subunit was not
      degraded, whereas a substantial degradation was observed in State 1. These
      results suggest that photoinhibition occurs via the generation of an intermediate
      state in which photosystem II is inactive but the D1 protein is still intact. The
      accumulation of this state is enhanced in State 2, because in this State only
      cyclic photosynthetic electron transport is active, whereas there is no electron
      flow between photosystem II and the cytochrome b(6)f complex (Finazzi, G., Furia,
      A., Barbagallo, R. P., and Forti, G. (1999) Biochim. Biophys. Acta 1413, 117
      129). The activity of photosystem I and of cytochrome b(6)f as well as the
      coupling of thylakoid membranes was not affected by illumination under the same
      conditions. This allows repairing the damages to photosystem II thanks to cell
      capacity to maintain a high rate of ATP synthesis (via photosystem I-driven
      cyclic electron flow). This capacity might represent an important physiological
      tool in protecting the photosynthetic apparatus from excess of light as well as
      from other a-biotic stress conditions.

PMID- 11294856
TI  - Reassembly of the tight junction after oxidative stress depends on tyrosine
      kinase activity.
AB  - Oxidative stress compromises the tight junction, but the mechanisms underlying
      its recovery remain unclear. We developed a model in which oxidative stress
      reversibly disrupts the tight junction. Exposure of Madin-Darby canine kidney
      cells to hydrogen peroxide markedly reduced transepithelial resistance and
      disrupted the staining patterns of the tight junction proteins ZO-1 and occludin.
      These changes were reversed by catalase. The short-term reassembly of tight
      junctions was not dependent on new protein synthesis, suggesting that recovery
      occurs through re-utilization of existing proteins. Although ATP levels were
      reduced, the reduction was insufficient to explain the observed changes, since a
      comparable reduction of ATP levels (with 2-deoxy-D-glucose) did not induce these
      changes. The intracellular hydrogen peroxide scavenger pyruvate protected Madin
      Darby canine kidney cells from loss of transepithelial resistance as did the
      heavy metal scavenger N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine. Of a
      wide variety of agents examined, only tyrosine kinase inhibitors and protein
      kinase C inhibitors markedly inhibited tight junction reassembly. During
      reassembly, tyrosine phosphorylation in or near the lateral membrane, was
      detected by immunofluorescence. The tyrosine kinase inhibitors genistein and PP-2
      inhibited the recovery of transepithelial resistance and perturbed the
      relocalization of ZO-1 and occludin to the tight junction, indicating that
      tyrosine kinases, possibly members of the Src family, are critical for reassembly
      after oxidative stress.

PMID- 11294857
TI  - Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell
      survival pathway in PC12 cells: protective role in apoptosis.
AB  - Hypoxia is a common environmental stress that influences signaling pathways and
      cell function. Several cell types, including neuroendocrine chromaffin cells,
      have evolved to sense oxygen levels and initiate specific adaptive responses to
      hypoxia. Here we report that under hypoxic conditions, rat pheochromocytoma PC12
      cells are resistant to apoptosis induced by serum withdrawal and chemotherapy
      treatment. This effect is also observed after treatment with deferoxamine, a
      compound that mimics many of the effects of hypoxia. The hypoxia-dependent
      protection from apoptosis correlates with activation of the phosphatidylinositol
      3-kinase (PI3K)/Akt pathway, which is detected after 3-4 h of hypoxic or
      deferoxamine treatment and is sustained while hypoxic conditions are maintained.
      Hypoxia-induced Akt activation can be prevented by treatment with cycloheximide
      or actinomycin D, suggesting that de novo protein synthesis is required. Finally,
      inhibition of PI3K impairs both the protection against apoptosis and the
      activation of Akt in response to hypoxia, suggesting a functional link between
      these two phenomena. Thus, reduced oxygen tension regulates apoptosis in PC12
      cells through activation of the PI3K/Akt survival pathway.

PMID- 11294858
TI  - Regulator of G-protein signaling 3 (RGS3) inhibits Gbeta1gamma 2-induced inositol
      phosphate production, mitogen-activated protein kinase activation, and Akt
      activation.
AB  - Regulator of G-protein signaling 3 (RGS3) enhances the intrinsic rate at which
      Galpha(i) and Galpha(q) hydrolyze GTP to GDP, thereby limiting the duration in
      which GTP-Galpha(i) and GTP-Galpha(q) can activate effectors. Since GDP-Galpha
      subunits rapidly combine with free Gbetagamma subunits to reform inactive
      heterotrimeric G-proteins, RGS3 and other RGS proteins may also reduce the amount
      of Gbetagamma subunits available for effector interactions. Although RGS6, RGS7,
      and RGS11 bind Gbeta(5) in the absence of a Ggamma subunit, RGS proteins are not
      known to directly influence Gbetagamma signaling. Here we show that RGS3 binds
      Gbeta(1)gamma(2) subunits and limits their ability to trigger the production of
      inositol phosphates and the activation of Akt and mitogen-activated protein
      kinase. Co-expression of RGS3 with Gbeta(1)gamma(2) inhibits Gbeta(1)gamma(2)
      induced inositol phosphate production and Akt activation in COS-7 cells and
      mitogen-activated protein kinase activation in HEK 293 cells. The inhibition of
      Gbeta(1)gamma(2) signaling does not require an intact RGS domain but depends upon
      two regions in RGS3 located between acids 313 and 390 and between 391 and 458.
      Several other RGS proteins do not affect Gbeta(1)gamma(2) signaling in these
      assays. Consistent with the in vivo results, RGS3 inhibits Gbetagamma-mediated
      activation of phospholipase Cbeta in vitro. Thus, RGS3 may limit Gbetagamma
      signaling not only by virtue of its GTPase-activating protein activity for Galpha
      subunits, but also by directly interfering with the activation of effectors.

PMID- 11294859
TI  - Association of AIM, a novel apoptosis inhibitory factor, with hepatitis via
      supporting macrophage survival and enhancing phagocytotic function of
      macrophages.
AB  - A hallmark of many inflammatory diseases is the destruction of tissue cells by
      infiltrating hematopoietic cells including lymphocytes, neutrophils, and
      macrophages. The regulation of apoptosis of both target tissue cells and the
      infiltrating cells is one of the key events that defines the initiation and the
      progression of inflammation. However, the precise picture of the apoptosis
      regulation of the cells at the inflammatory sites is still unclear. We recently
      isolated a novel apoptosis inhibitory factor, termed AIM, which is secreted
      exclusively by tissue macrophages. In this report, we present unique
      characteristics of AIM associated with liver inflammation (hepatitis), identified
      by introducing an experimental hepatitis in both AIM-transgenic mice, which
      overexpress AIM in the body, and normal mice. First, endogenous AIM expression in
      macrophages is rapidly increased in response to inflammatory stimuli. Second, AIM
      appears to inhibit the death of macrophages in the inflammatory regions, judging
      by the remarkably increased number of macrophages observed in the liver from
      transgenic mice. In addition, we show that AIM also enhances the phagocytosis by
      macrophages, which emphasizes the multifunctional character of AIM. All these
      findings strongly provoke an idea that AIM may play an important role in
      hepatitis pathogenesis in a sequential manner; first AIM expression is up
      regulated by inflammatory stimuli, and then in an autocrine fashion, AIM supports
      the survival of infiltrating macrophages as well as enhances phagocytosis by
      macrophages, which may result in an efficient clearance of dead cells and
      infectious or toxic reagents.

PMID- 11294860
TI  - Apoptosis induces efflux of the mitochondrial matrix enzyme deoxyguanosine
      kinase.
AB  - Deoxyguanosine kinase (dGK) initiates the salvage of purine deoxynucleosides in
      mitochondria and is a key enzyme in mitochondrial DNA precursor synthesis. The
      active form of the enzyme is a 60-kDa protein normally located in the
      mitochondrial matrix. Here we describe the subcellular distribution of dGK during
      apoptosis in human epithelial kidney 293 cells and human lymphoblast Molt-4
      cells. Immunological methods were used to monitor dGK as well as other
      mitochondrial proteins. Surprisingly, dGK was found to relocate to the cytosolic
      compartment at a similar rate as cytochrome c, a mitochondrial intermembraneous
      enzyme known to enter the cytosol early in apoptosis. The redistribution of dGK
      from the mitochondria to the cytosol may be of importance for the activation of
      apoptotic purine nucleoside cofactors such as dATP and demonstrates that
      mitochondrial matrix proteins may selectively leak out during apoptosis.

PMID- 11294861
TI  - Coupling of voltage-dependent potassium channel inactivation and oxidoreductase
      active site of Kvbeta subunits.
AB  - The accessory beta subunits of voltage-dependent potassium (Kv) channels form
      tetramers arranged with 4-fold rotational symmetry like the membrane-integral and
      pore-forming alpha subunits (Gulbis, J. M., Mann, S., and MacKinnon, R. (1999)
      Cell. 90, 943-952). The crystal structure of the Kvbeta2 subunit shows that
      Kvbeta subunits are oxidoreductase enzymes containing an active site composed of
      conserved catalytic residues, a nicotinamide (NADPH)-cofactor, and a substrate
      binding site. Also, Kvbeta subunits with an N-terminal inactivating domain like
      Kvbeta1.1 (Rettig, J., Heinemann, S. H., Wunder, F., Lorra, C., Parcej, D. N.,
      Dolly, O., and Pongs, O. (1994) Nature 369, 289-294) and Kvbeta3.1 (Heinemann, S.
      H., Rettig, J., Graack, H. R., and Pongs, O. (1996) J. Physiol. (Lond.) 493, 625
      633) confer rapid N-type inactivation to otherwise non-inactivating channels.
      Here we show by a combination of structural modeling and electrophysiological
      characterization of structure-based mutations that changes in Kvbeta
      oxidoreductase activity may markedly influence the gating mode of Kv channels.
      Amino acid substitutions of the putative catalytic residues in the Kvbeta1.1
      oxidoreductase active site attenuate the inactivating activity of Kvbeta1.1 in
      Xenopus oocytes. Conversely, mutating the substrate binding domain and/or the
      cofactor binding domain rescues the failure of Kvbeta3.1 to confer rapid
      inactivation to Kv1.5 channels in Xenopus oocytes. We propose that Kvbeta
      oxidoreductase activity couples Kv channel inactivation to cellular redox
      regulation.

PMID- 11294862
TI  - Regulation of the glycophorin C-protein 4.1 membrane-to-skeleton bridge and
      evaluation of its contribution to erythrocyte membrane stability.
AB  - The band 3-ankyrin-spectrin bridge and the glycophorin C-protein 4.1
      spectrin/actin bridge constitute the two major tethers between the erythrocyte
      membrane and its spectrin skeleton. Although a structural requirement for the
      band 3-ankyrin bridge is well established, the contribution of the glycophorin C
      protein 4.1 bridge to red cell function remains to be defined. In order to
      explore this latter bridge further, we have identified and/or characterized five
      stimuli that sever the linkage in intact erythrocytes and have examined the
      impact of this rupture on membrane mechanical properties. We report here that
      elevation of cytosolic 2,3-bisphosphoglycerate, an increase in intracellular
      Ca(2+), removal of cell O(2), a decrease in intracellular pH, and activation of
      erythrocyte protein kinase C all promote dissociation of protein 4.1 from
      glycophorin C, leading to reduced retention of glycophorin C in detergent
      extracted spectrin/actin skeletons. Significantly, where mechanical studies could
      be performed, we also observe that rupture of the membrane-to-skeleton bridge has
      little or no impact on the mechanical properties of the cell, as assayed by
      ektacytometry and nickel mesh filtration. We, therefore, suggest that, although
      regulation of the glycophorin C-protein 4.1-spectrin/actin bridge likely occurs
      physiologically, the role of the tether and the associated regulatory changes
      remain to be established.

PMID- 11294863
TI  - Structure of a pilin monomer from Pseudomonas aeruginosa: implications for the
      assembly of pili.
AB  - Type IV pilin monomers assemble to form fibers called pili that are required for
      a variety of bacterial functions. Pilin monomers oligomerize due to the
      interaction of part of their hydrophobic N-terminal alpha-helix. Engineering of a
      truncated pilin from Pseudomonas aeruginosa strain K122-4, where the first 28
      residues are removed from the N terminus, yields a soluble, monomeric protein.
      This truncated pilin is shown to bind to its receptor and to decrease morbidity
      and mortality in mice upon administration 15 min before challenge with a
      heterologous strain of Pseudomonas. The structure of this truncated pilin reveals
      an alpha-helix at the N terminus that lies across a 4-stranded antiparallel beta
      sheet. A model for a pilus is proposed that takes into account both electrostatic
      and hydrophobic interactions of pilin subunits as well as previously published x
      ray fiber diffraction data. Our model indicates that DNA or RNA cannot pass
      through the center of the pilus, however, the possibility exists for small
      organic molecules to pass through indicating a potential mechanism for signal
      transduction.

PMID- 11294864
TI  - Interactions of calmodulin with two peptides derived from the c-terminal
      cytoplasmic domain of the Ca(v)1.2 Ca2+ channel provide evidence for a molecular
      switch involved in Ca2+-induced inactivation.
AB  - When opened by depolarization, L-type calcium channels are rapidly inactivated by
      the elevation of Ca(2+) concentration on the cytoplasmic side. Recent studies
      have shown that the interaction of calmodulin with the proximal part of the
      cytoplasmic C-terminal tail of the channel plays a prominent role in this
      modulation. Two motifs interacting with calmodulin in a Ca(2+)-dependent manner
      have been described: the IQ sequence and more recently the neighboring CB
      sequence. Here, using synthetic peptides and fusion proteins derived from the
      Ca(v)1.2 channel combined with biochemical techniques, we show that these two
      peptides are the only motifs of the cytoplasmic tail susceptible to interact with
      calmodulin. We determined the K(d) of the CB interaction with calmodulin to be 12
      nm, i.e. below the K(d) of IQ-calmodulin, thereby precluding a competitive
      displacement of CB by IQ in the presence of Ca(2+). In place, we demonstrated
      that a ternary complex is formed at high Ca(2+) concentration, provided that
      calmodulin and the peptides are initially allowed to interact at a low Ca(2+)
      concentration. These results provide evidence that CB and IQ motifs interacting
      together with calmodulin constitute a minimal molecular switch leading to Ca(2+)
      induced inactivation. In addition, we suggest that they could also be the
      tethering site of calmodulin.

PMID- 11294865
TI  - Hagfish hemoglobins: structure, function, and oxygen-linked association.
AB  - Cyclostomes, hagfishes and lampreys, contain hemoglobins that are monomeric when
      oxygenated and polymerize to dimers or tetramers when deoxygenated. The three
      major hemoglobin components (HbI, HbII, and HbIII) from the hagfish Myxine
      glutinosa have been characterized and compared with lamprey Petromyzon marinus
      HbV, whose x-ray crystal structure has been solved in the deoxygenated, dimeric
      state (Heaslet, H. A., and Royer, W. E., Jr. (1999) Structure 7, 517-526). Of
      these three, HbII bears the highest sequence similarity to P. marinus HbV. In HbI
      and HbIII the distal histidine is substituted by a glutamine residue and
      additional substitutions occur in residues located at the deoxy dimer interface
      of P. marinus HbV. Infrared spectroscopy of the CO derivatives, used to probe the
      distal pocket fine structure, brings out a correlation between the CO stretching
      frequencies and the rates of CO combination. Ultracentrifugation studies show
      that HbI and HbIII are monomeric in both the oxygenated and deoxygenated states
      under all conditions studied, whereas deoxy HbII forms dimers at acidic pH
      values, like P. marinus HbV. Accordingly, the oxygen affinities of HbI and HbIII
      are independent of pH, whereas HbII displays a Bohr effect below pH 7.2. HbII
      also forms heterodimers with HbIII and heterotetramers with HbI. The functional
      counterparts of heteropolymer formation are cooperativity in oxygen binding and
      the oxygen-linked binding of protons and bicarbonate. The observed effects are
      explained on the basis of the x-ray structure of P. marinus HbV and the
      association behavior of site-specific mutants (Qiu, Y., Maillett, D. H., Knapp,
      J., Olson, J. S., and Riggs, A. F. (2000) J. Biol. Chem. 275, 13517-13528).

PMID- 11294866
TI  - Evidence for spatial proximity of two distinct receptor regions in the substance
      P (SP)*neurokinin-1 receptor (NK-1R) complex obtained by photolabeling the NK-1R
      with p-benzoylphenylalanine3-SP.
AB  - Substance P (SP) belongs to the tachykinin family of bioactive peptides and
      exerts its many biological effects through functional interaction with its cell
      surface, G protein-coupled neurokinin-1 receptor (NK-1R). Previous studies from
      our laboratory have shown that (125)I-Bolton-Hunter reagent-labeled p
      benzoylphenylalanine(8)-SP (Bpa(8)SP) covalently attaches to Met(181), whereas
      (125)I-Bolton-Hunter reagent-labeled Bpa(4)SP covalently attaches to Met(174),
      both of which are located on the second extracellular loop (EC2) of the NK-1R. In
      this study, evidence has been obtained that at equilibrium, the photoreactive SP
      analogue (125)I-[D-Tyr(0)]Bpa(3)SP covalently labels residues in two distinct
      extracellular regions of the NK-1R. One site of (125)I-[D-Tyr(0)]Bpa(3)SP
      photoinsertion is located on EC2 within a segment of the receptor extending from
      residues 173 to 177; a second site of (125)I-[D-Tyr(0)]Bpa(3)SP photoinsertion is
      located on the extracellular N terminus within a segment of the receptor
      extending from residues 11 to 21, a sequence that contains both potential sites
      for N-linked glycosylation. Since competition binding data presented in this
      study do not suggest the existence of multiple peptide.NK-1R complexes, it is
      reasonable to assume that the receptor sequences within EC2 and N terminus
      identified by peptide mapping are in close proximity in the equilibrium complex.

PMID- 11294867
TI  - Activation and functional characterization of the mosaic receptor SorLA/LR11.
AB  - We previously isolated and sequenced the approximately 250-kDa type 1 receptor
      sorLA/LR11, a mosaic protein with elements characterizing the Vps10p domain
      receptor family as well as the low density lipoprotein receptor family. The N
      terminus of the Vps10p domain comprises a consensus sequence for cleavage by
      furin ((50)RRKR(53)) that precedes a truncation found in sorLA isolated from
      human brain. Here we show that sorLA, like sortilin-1/neurotensin receptor-3,
      whose lumenal domain consists of a Vps10p domain only, is synthesized as a
      proreceptor that is cleaved by furin in late Golgi compartments. We show that the
      truncation conditions the Vps10p domain for propeptide inhibitable binding of
      neuropeptides and the receptor-associated protein. We further demonstrate that
      avid binding of the receptor-associated protein, apolipoprotein E, and
      lipoprotein lipase not inhibited by propeptide occurs to sites located in other
      lumenal domains. In transfected cells, about 10% of full-length sorLA were
      expressed on the cell surface capable of mediating endocytosis. However, the
      major pool of receptors was found in late Golgi compartments, suggesting possible
      interaction with newly synthesized ligands. The results show that sorLA,
      following activation by truncation, binds multiple ligands and may mediate both
      endocytosis and sorting.

PMID- 11294868
TI  - Microarray analysis reveals previously unknown changes in Toxoplasma gondii
      infected human cells.
AB  - Cells infected with the intracellular protozoan parasite Toxoplasma gondii
      undergo up-regulation of pro-inflammatory cytokines, organelle redistribution,
      and protection from apoptosis. To examine the molecular basis of these and other
      changes, gene expression profiles of human foreskin fibroblasts infected with
      Toxoplasma were studied using human cDNA microarrays consisting of approximately
      22,000 known genes and uncharacterized expressed sequence tags. Early during
      infection (1-2 h), <1% of all genes show a significant change in the abundance of
      their transcripts. Of the 63 known genes in this group, 27 encode proteins
      associated with the immune response. These genes are also up-regulated by
      secreted, soluble factors from extracellular parasites indicating that the early
      response does not require parasite invasion. Later during infection, genes
      involved in numerous host cell processes, including glucose and mevalonate
      metabolism, are modulated. Many of these late genes are dependent on the direct
      presence of the parasite; i.e. secreted products from either the parasite or
      infected cells are insufficient to induce these changes. These results reveal
      several previously unknown effects on the host cell and lay the foundation for
      detailed analysis of their role in the host-pathogen interaction.

PMID- 11294870
TI  - Characterization of elongation factor-1A (eEF1A-1) and eEF1A-2/S1 protein
      expression in normal and wasted mice.
AB  - The eEF1Alpha-2 gene (S1) encodes a tissue-specific isoform of peptide elongation
      factor-1A (eEF1A-1); its mRNA is expressed only in brain, heart, and skeletal
      muscle, tissues dominated by terminally differentiated, long-lived cells.
      Homozygous mutant mice exhibit muscle wasting and neurodegeneration, resulting in
      death around postnatal day 28. eEF1Alpha-2/S1 protein shares 92% identity with
      eEF1A-1; because specific antibodies for each were not available previously, it
      was difficult to study the developmental expression patterns of these two peptide
      elongation factors 1A in wasted and wild-type mice. We generated a peptide
      derived antiserum that recognizes the eEF1Alpha-2/S1 isoform and does not cross
      react with eEF1A-1. We characterized the expression profiles of eEF1A-1 and eEF1A
      2/S1 during development in wild-type (+/+), heterozygous (+/wst), and homozygous
      (wst/wst) mice. In wild-type and heterozygous animals, eEF1A-2/S1 protein is
      present only in brain, heart, and muscle; the onset of its expression coincides
      with a concomitant decrease in the eEF1A-1 protein level. In wasted mutant
      tissues, even though eEF1A-2/S1 protein is absent, the scheduled decline of eEF1A
      1 occurs nonetheless during postnatal development, as it does in wild-type
      counterparts. In the brain of adult wild-type mice, the eEF1A-2/S1 isoform is
      localized in neurons, whereas eEF1A-1 is found in non-neuronal cells. In neurons
      prior to postnatal day 7, eEF1A-1 is the major isoform, but it is later replaced
      by eEF1A-2/S1, which by postnatal day 14 is the only isoform present. The
      postdevelopmental appearance of eEF1A-2/S1 protein and the decline in eEF1A-1
      expression in brain, heart, and muscle suggest that eEF1A-2/S1 is the adult form
      of peptide elongation factor, whereas its sister is the embryonic isoform, in
      these tissues. The absence of eEF1A-2/S1, as well as the on-schedule development
      dependent disappearance of its sister gene, eEF1A, in wst/wst mice may result in
      loss of protein synthesis ability, which may account for the numerous defects and
      ultimate fatality seen in these mice.

PMID- 11294871
TI  - Molecular characterization of the substance P*neurokinin-1 receptor complex:
      development of an experimentally based model.
AB  - Molecular models for the interaction of substance P (SP) with its G protein
      coupled receptor, the neurokinin-1 receptor (NK-1R), have been developed. The
      ligand.receptor complex is based on experimental data from a series of
      photoaffinity labeling experiments and spectroscopic structural studies of
      extracellular domains of the NK-1R. Using the ligand/receptor contact points
      derived from incorporation of photolabile probes (p-benzoylphenylalanine (Bpa))
      into SP at positions 3, 4, and 8 and molecular dynamics simulations, the
      topological arrangement of SP within the NK-1R is explored. The model
      incorporates the structural features, determined by high resolution NMR studies,
      of the second extracellular loop (EC2), containing contact points Met(174) and
      Met(181), providing important experimentally based conformational preferences for
      the simulations. Extensive molecular dynamics simulations were carried out to
      probe the nature of the two contact points identified for the Bpa(3)SP analogue
      (Bremer, A. A., Leeman, S. E., and Boyd, N. D. (2001) J. Biol. Chem. 276, 22857
      22861), examining modes of ligand binding in which the contact points are
      fulfilled sequentially or simultaneously. The resulting ligand.receptor complex
      has the N terminus of SP projecting toward transmembrane helix (TM) 1 and TM2,
      exposed to the solvent. The C terminus of SP is located in proximity to TM5 and
      TM6, deeper into the central core of the receptor. The central portion of the
      ligand, adopting a helical loop conformation, is found to align with the helices
      of the central regions EC2 and EC3, forming important interactions with both of
      these extracellular domains. The model developed here allows for atomic insight
      into the biochemical data currently available and guides targeting of future
      experiments to probe specific ligand/receptor interactions and thereby furthers
      our understanding of the functioning of this important neuropeptide system.

PMID- 11294872
TI  - Role of extracellular molecular chaperones in the folding of oxidized proteins.
      Refolding of colloidal thyroglobulin by protein disulfide isomerase and
      immunoglobulin heavy chain-binding protein.
AB  - The process of thyroid hormone synthesis, which occurs in the lumen of the
      thyroid follicles, results from an oxidative reaction leading, as side effects,
      to the multimerization of thyroglobulin (TG), the prothyroid hormone. Although
      hormone synthesis is a continuous process, the amount of Tg multimers is
      relatively constant. Here, we investigated the role of two molecular chaperones,
      protein disulfide isomerase (PDI) and immunoglobulin heavy chain-binding protein
      (BiP), present in the follicular lumen, on the multimerization process due to
      oxidation using both native Tg and its N-terminal domain (NTD). In vitro, PDI
      decreased multimerization of Tg and even suppressed the formation of NTD
      multimers. Under the same conditions, BiP was able to bind to Tg and NTD
      multimers but did not affect the process of multimerization. Associating BiP with
      PDI did not enhance the ability of PDI to limit the formation of multimers
      produced by oxidation. However, when BiP and PDI were reacted together with the
      multimeric forms and for a longer time (48 h), BiP greatly increased the
      efficiency of PDI. Accordingly, these two molecular chaperones probably act
      sequentially on the reduction of the intermolecular disulfide bridges. In the
      thyroid, a similar process may also be effective and participate in limiting the
      amount of Tg multimers present in the colloid. These results suggest that
      extracellular molecular chaperones play a similar role to that occurring in the
      endoplasmic reticulum and, furthermore, take part in the control of
      multimerization and aggregation of proteins formed by oxidation.

PMID- 11294873
TI  - Gbeta gamma isoforms selectively rescue plasma membrane localization and
      palmitoylation of mutant Galphas and Galphaq.
AB  - Mutation of Galpha(q) or Galpha(s) N-terminal contact sites for Gbetagamma
      resulted in alpha subunits that failed to localize at the plasma membrane or
      undergo palmitoylation when expressed in HEK293 cells. We now show that
      overexpression of specific betagamma subunits can recover plasma membrane
      localization and palmitoylation of the betagamma-binding-deficient mutants of
      alpha(s) or alpha(q). Thus, the betagamma-binding-defective alpha is completely
      dependent on co-expression of exogenous betagamma for proper membrane
      localization. In this report, we examined the ability of beta(1-5) in combination
      with gamma(2) or gamma(3) to promote proper localization and palmitoylation of
      mutant alpha(s) or alpha(q). Immunofluorescence localization, cellular
      fractionation, and palmitate labeling revealed distinct subtype-specific
      differences in betagamma interactions with alpha subunits. These studies
      demonstrate that 1) alpha and betagamma reciprocally promote the plasma membrane
      targeting of the other subunit; 2) beta(5), when co-expressed with gamma(2) or
      gamma(3), fails to localize to the plasma membrane or promote plasma membrane
      localization of mutant alpha(s) or alpha(q); 3) beta(3) is deficient in promoting
      plasma membrane localization of mutant alpha(s) and alpha(q), whereas beta(4) is
      deficient in promoting plasma membrane localization of mutant alpha(q); 4) both
      palmitoylation and interactions with betagamma are required for plasma membrane
      localization of alpha.

PMID- 11294874
TI  - A novel plasmal conjugate to glycerol and psychosine
      ("glyceroplasmalopsychosine"): isolation and characterization from bovine brain
      white matter.
AB  - A novel plasmal conjugate of glycosphingolipid having cationic lipid properties
      was isolated from the white matter of bovine brain. Linkage analysis of
      galactosyl residue by methylation, liquid secondary ion, and electrospray
      ionization mass spectrometry of intact and methylated derivatives, and by (1)H-
      and (13)C-NMR spectroscopy, identified the structure unambiguously as an O-acetal
      conjugate of plasmal to the primary hydroxyl group of glycerol and to the 6
      hydroxyl group of galactosyl residue of beta-galactosyl 1-->1 sphingosine
      (psychosine). This novel compound is hereby termed "glyceroplasmalopsychosine";
      its structure is shown below (see text).

PMID- 11294875
TI  - Minimal functional structure of Escherichia coli 4.5 S RNA required for binding
      to elongation factor G.
AB  - Escherichia coli cells contain abundant amounts of metabolically stable 4.5 S
      RNA. Consisting of 114 nucleotides, 4.5 S RNA is structurally homologous to
      mammalian 7 S RNA, and it plays an essential role in targeting proteins
      containing signal peptide to the secretory apparatus by forming an signal
      recognition-like particle with Ffh protein. It also binds independently to
      protein elongation factor G (EF-G) and functions in the translation process. This
      RNA contains a phylogenetically conserved RNA domain, the predicted secondary
      structure of which consists of a hairpin motif with two bulges. We examined the
      binding activity of mutants with systematic deletions to define the minimal
      functional interaction domain of 4.5 S RNA that interacts with EF-G. This domain
      consisted of 35-nucleotides extending from 36 to 70 nucleotides of mature 4.5 S
      RNA and contained two conserved bulges in which mutations of A47, A60, G61, C62,
      A63, and A67 diminished binding to EF-G, whereas those at A39, C40, C41, A42,
      G48, and G49 did not affect binding. These data suggested that the 10 nucleotides
      in 4.5 S RNA, which are conserved between 4.5 S RNA and 23 S rRNA, have a key
      role for EF-G binding. Based on the NMR-derived structure of mutant A47U, we
      further verified that substituting U at A47 causes striking structural changes
      and the loss of the symmetrical bulge. These results indicate the mechanism by
      which EF-G interacts with 4.5 S RNA and the importance of the bulge structure for
      EF-G binding.

PMID- 11294876
TI  - Ethylbenzene dehydrogenase, a novel hydrocarbon-oxidizing molybdenum/iron
      sulfur/heme enzyme.
AB  - The initial enzyme of ethylbenzene metabolism in denitrifying Azoarcus strain
      EbN1, ethylbenzene dehydrogenase, was purified and characterized. The soluble
      periplasmic enzyme is the first known enzyme oxidizing a nonactivated hydrocarbon
      without molecular oxygen as cosubstrate. It is a novel molybdenum/iron
      sulfur/heme protein of 155 kDa, which consists of three subunits (96, 43, and 23
      kDa) in an alphabetagamma structure. The N-terminal amino acid sequence of the
      alpha subunit is similar to that of other molybdenum proteins such as selenate
      reductase from the related species Thauera selenatis. Ethylbenzene dehydrogenase
      is unique in that it oxidizes the hydrocarbon ethylbenzene, a compound without
      functional groups, to (S)-1-phenylethanol. Formation of the product was evident
      by coupling to an enantiomer-specific (S)-1-phenylethanol dehydrogenase from the
      same organism. The apparent K(m) of the enzyme for ethylbenzene is very low at <2
      microm. Oxygen does not affect ethylbenzene dehydrogenase activity in extracts
      but inactivates the purified enzyme, if the heme b cofactor is in the reduced
      state. A variant of ethylbenzene dehydrogenase exhibiting significant activity
      also with the homolog n-propylbenzene was detected in a related Azoarcus strain
      (PbN1).

PMID- 11294877
TI  - Identification of zeta-crystallin/NADPH:quinone reductase as a renal glutaminase
      mRNA pH response element-binding protein.
AB  - Increased renal ammoniagenesis and bicarbonate synthesis from glutamine during
      chronic metabolic acidosis facilitate the excretion of acids and partially
      restore normal acid-base balance. This adaptation is sustained, in part, by a
      cell-specific stabilization of the glutaminase mRNA that leads to an increased
      synthesis of the mitochondrial glutaminase. A direct repeat of an 8-base AU
      sequence within the 3'-nontranslated region of the glutaminase mRNA binds a
      unique protein with high affinity and specificity. Expression of various chimeric
      mRNAs in LLC-PK(1)-FBPase(+) cells demonstrated that a single 8-base AU sequence
      is both necessary and sufficient to function as a pH response element (pH RE). A
      biotinylated oligoribonucleotide containing the direct repeat was used as an
      affinity ligand to purify the pH RE-binding protein from a cytosolic extract of
      rat renal cortex. The purified binding activity retained the same specific
      binding properties as observed with crude extracts and correlated with the
      elution of a 36-kDa protein. Microsequencing by mass spectroscopy and Western
      blot analysis were used to identify this protein as zeta-crystallin/NADPH:quinone
      reductase. The purified protein contained eight tryptic peptides that were
      identical to sequences found in mouse zeta-crystallin and three peptides that
      differed by only a single amino acid. The observed differences may represent
      substitutions found in the rat homolog. A second protein purified by this
      protocol was identified as T-cell-restricted intracellular antigen-related
      protein (TIAR). However, the purified TIAR neither bound nor affected the binding
      of zeta-crystallin/NADPH:quinone reductase to the pH RE. Furthermore, specific
      antibodies to zeta-crystallin, but not TIAR, blocked the formation of the complex
      between the pH RE and either the crude cytosolic extract or the purified protein.
      Thus, zeta-crystallin/NADPH:quinone reductase is a pH response element-binding
      protein.

PMID- 11294878
TI  - Characterization of a novel type of human microsomal 3alpha -hydroxysteroid
      dehydrogenase: unique tissue distribution and catalytic properties.
AB  - We report characterization of a novel member of the short chain
      dehydrogenase/reductase superfamily. The 1513-base pair cDNA encodes a 319-amino
      acid protein. The corresponding gene spans over 26 kilobase pairs on chromosome 2
      and contains five exons. The recombinant protein produced using the baculovirus
      system is localized in the microsomal fraction of Sf9 cells and is an integral
      membrane protein with cytosolic orientation of its catalytic domain. The enzyme
      exhibits an oxidoreductase activity toward hydroxysteroids with NAD(+) and NADH
      as the preferred cofactors. The enzyme is most efficient as a 3alpha
      hydroxysteroid dehydrogenase, converting 3alpha-tetrahydroprogesterone
      (allopregnanolone) to dihydroprogesterone and 3alpha-androstanediol to
      dihydrotestosterone with similar catalytic efficiency (V(max) values of 13-14
      nmol/min/mg microsomal protein and K(m) values of 5-7 microm). Despite
      approximately 44-47% sequence identity with retinol/3alpha-hydroxysterol
      dehydrogenases, the enzyme is not active toward retinols. The corresponding
      message is abundant in human trachea and is present at lower levels in the spinal
      cord, bone marrow, brain, heart, colon, testis, placenta, lung, and lymph node.
      Thus, the new short chain dehydrogenase represents a novel type of microsomal
      NAD(+)-dependent 3alpha-hydroxysteroid dehydrogenase with unique catalytic
      properties and tissue distribution.

PMID- 11294879
TI  - Engineering delta 9-16:0-acyl carrier protein (ACP) desaturase specificity based
      on combinatorial saturation mutagenesis and logical redesign of the castor delta
      9-18:0-ACP desaturase.
AB  - Six amino acid locations in the soluble castor Delta(9)-18:0-acyl carrier protein
      (ACP) desaturase were identified that can affect substrate specificity.
      Combinatorial saturation mutagenesis of these six amino acids, in conjunction
      with selection, using an unsaturated fatty acid auxotroph system, led to the
      isolation of variants with up to 15-fold increased specific activity toward 16
      carbon substrates. The most improved mutant, com2, contained two substitutions
      (T117R/G188L) common to five of the 19 complementing variants subjected to
      further analysis. These changes, when engineered into otherwise wild-type 18:0
      ACP desaturase to make mutant 5.2, produced a 35-fold increase in specific
      activity with respect to 16-carbon substrates. Kinetic analysis revealed changes
      in both k(cat) and K(m) that result in an 82-fold improvement in specificity
      factor for 16-carbon substrate compared with wild-type enzyme. Improved substrate
      orientation apparently compensated for loss of binding energy that results from
      the loss of desolvation energy for 16-carbon substrates. Mutant 5.2 had specific
      activity for 16-carbon substrates 2 orders of magnitude higher than those of
      known natural 16-carbon specific desaturases. These data support the hypothesis
      that it should be possible to reengineer archetypal enzymes to achieve substrate
      specificities characteristic of recently evolved enzymes while retaining the
      desired stability and/or turnover characteristics of a parental paralog.

PMID- 11294880
TI  - Molecular cloning of a third member of the potassium-dependent sodium-calcium
      exchanger gene family, NCKX3.
AB  - We describe here the identification and characterization of a novel member of the
      family of K(+)-dependent Na(+)/Ca(2+) exchangers, NCKX3 (gene SLC24A3). Human
      NCKX3 encodes a protein of 644 amino acids that displayed a high level of
      sequence identity to the other family members, rod NCKX1 and cone/neuronal NCKX2,
      in the hydrophobic regions surrounding the "alpha -repeat" sequences thought to
      form the ion-binding pocket for transport. Outside of these regions NCKX3 showed
      no significant identity to other known proteins. As anticipated from this
      sequence similarity, NCKX3 displayed K(+)-dependent Na(+)/Ca(2+) exchanger
      activity when assayed in heterologous expression systems, using digital imaging
      of fura-2 fluorescence, electrophysiology, or radioactive (45)Ca(2+) uptake. The
      N-terminal region of NCKX3, although not essential for expression, increased
      functional activity at least 10-fold and may represent a cleavable signal
      sequence. NCKX3 transcripts were most abundant in brain, with highest levels
      found in selected thalamic nuclei, in hippocampal CA1 neurons, and in layer IV of
      the cerebral cortex. Many other tissues also expressed NCKX3 at lower levels,
      especially aorta, uterus, and intestine, which are rich in smooth muscle. The
      discovery of NCKX3 thus expands the K(+)-dependent Na(+)/Ca(2+) exchanger family
      and suggests this class of transporter has a more widespread role in cellular
      Ca(2+) handling than previously appreciated.

PMID- 11294881
TI  - High field EPR study of the pheophytin anion radical in wild type and D1-E130
      mutants of photosystem II in Chlamydomonas reinhardtii.
AB  - The intermediate electron acceptor in photosystem II is a pheophytin molecule.
      The radical anion of this molecule was studied using high field electron
      paramagnetic resonance in a series of Chlamydomonas reinhardtii mutants. Glutamic
      acid 130 of the D1 polypeptide is thought to hydrogen bond the ring V carbonyl
      group of this radical. Mutations at this site, designed to weaken or remove this
      hydrogen bond, strongly affected the g tensor of the radical. The upward shift of
      the g(x) component followed the decreasing hydrogen bonding capacity of the amino
      acid introduced. This behavior is similar to that of tyrosyl and semiquinone
      radicals. It is also consistent with the optical spectra of the pheophytin in
      similar mutants. Density functional calculations were used to calculate the g
      tensors and rationalize the observed trend in the variation of the g(x) value for
      pheophytin and bacteriopheophytin radical. The theoretical results support the
      experimental observations and demonstrate the sensitivity of g values to the
      electrostatic protein environment for these types of radicals.

PMID- 11294884
TI  - What mitochondria have told me.

PMID- 11294886
TI  - A millennial myosin census.
AB  - The past decade has seen a remarkable explosion in our knowledge of the size and
      diversity of the myosin superfamily. Since these actin-based motors are
      candidates to provide the molecular basis for many cellular movements, it is
      essential that motility researchers be aware of the complete set of myosins in a
      given organism. The availability of cDNA and/or draft genomic sequences from
      humans, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana,
      Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Dictyostelium discoideum
      has allowed us to tentatively define and compare the sets of myosin genes in
      these organisms. This analysis has also led to the identification of several
      putative myosin genes that may be of general interest. In humans, for example, we
      find a total of 40 known or predicted myosin genes including two new myosins-I,
      three new class II (conventional) myosins, a second member of the class III/ninaC
      myosins, a gene similar to the class XV deafness myosin, and a novel myosin
      sharing at most 33% identity with other members of the superfamily. These myosins
      are in addition to the recently discovered class XVI myosin with N-terminal
      ankyrin repeats and two human genes with similarity to the class XVIII PDZ-myosin
      from mouse. We briefly describe these newly recognized myosins and extend our
      previous phylogenetic analysis of the myosin superfamily to include a comparison
      of the complete or nearly complete inventories of myosin genes from several
      experimentally important organisms.

PMID- 11294887
TI  - Golgi complex reorganization during muscle differentiation: visualization in
      living cells and mechanism.
AB  - During skeletal muscle differentiation, the Golgi complex (GC) undergoes a
      dramatic reorganization. We have now visualized the differentiation and fusion of
      living myoblasts of the mouse muscle cell line C2, permanently expressing a
      mannosidase-green fluorescent protein (GFP) construct. These experiments reveal
      that the reorganization of the GC is progressive (1-2 h) and is completed before
      the cells start fusing. Fluorescence recovery after photobleaching (FRAP),
      immunofluorescence, and immunogold electron microscopy demonstrate that the GC is
      fragmented into elements localized near the endoplasmic reticulum (ER) exit
      sites. FRAP analysis and the ER relocation of endogenous GC proteins by
      phospholipase A2 inhibitors demonstrate that Golgi-ER cycling of resident GC
      proteins takes place in both myoblasts and myotubes. All results support a model
      in which the GC reorganization in muscle reflects changes in the Golgi-ER
      cycling. The mechanism is similar to that leading to the dispersal of the GC
      caused, in all mammalian cells, by microtubule-disrupting drugs. We propose that
      the trigger for the dispersal results, in muscle, from combined changes in
      microtubule nucleation and ER exit site localization, which place the ER exit
      sites near microtubule minus ends. Thus, changes in GC organization that
      initially appear specific to muscle cells, in fact use pathways common to all
      mammalian cells.

PMID- 11294888
TI  - Sequence-specific interaction between the disintegrin domain of mouse ADAM 3 and
      murine eggs: role of beta1 integrin-associated proteins CD9, CD81, and CD98.
AB  - ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg
      adhesion. Because little is known about the adhesive activity of ADAMs, we
      investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and
      in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg
      binding and fusion with potencies similar to that which we recently reported for
      the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical
      importance for the glutamine at position 7 of the disintegrin loop. Fluorescent
      beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead
      binding was inhibited by an authentic, but not by a scrambled, peptide analog of
      the disintegrin loop. Bead binding was also inhibited by the function-blocking
      anti-alpha6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking
      anti-alpha6 mAb, or by mAbs against either the alphav or beta3 integrin subunits.
      We also present evidence that in addition to the tetraspanin CD9, two other beta1
      integrin-associated proteins, the tetraspanin CD81 as well as the single pass
      transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and
      CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin
      domain. Our findings are discussed in terms of the involvement of multiple sperm
      ADAMs and multiple egg beta1 integrin-associated proteins in sperm-egg binding
      and fusion. We propose that an egg surface "tetraspan web" facilitates
      fertilization and that it may do so by fostering ADAM-integrin interactions.

PMID- 11294890
TI  - Inhibition of endothelial wound repair by dominant negative connexin inhibitors.
AB  - Wounding of endothelial cells is associated with altered direct intercellular
      communication. To determine whether gap junctional communication participates to
      the wound repair process, we have compared connexin (Cx) expression, cell-to-cell
      coupling and kinetics of wound repair in monolayer cultures of PymT-transformed
      mouse endothelial cells (clone bEnd.3) and in bEnd.3 cells expressing different
      dominant negative Cx inhibitors. In parental bEnd.3 cells, mechanical wounding
      increased expression of Cx43 and decreased expression of Cx37 at the site of
      injury, whereas Cx40 expression was unaffected. These wound-induced changes in Cx
      expression were associated with functional changes in cell-to-cell coupling, as
      assessed with different fluorescent tracers. Stable transfection with cDNAs
      encoding for the chimeric connexin 3243H7 or the fusion protein Cx43-betaGal
      resulted in perturbed gap junctional communication between bEnd.3 cells under
      both basal and wounded conditions. The time required for complete repair of a
      defined wound within a confluent monolayer was increased by ~50% in cells
      expressing the dominant negative Cx inhibitors, whereas other cell properties,
      such as proliferation rate, migration of single cells, cyst formation and
      extracellular proteolytic activity, were unaltered. These findings demonstrate
      that proper Cx expression is required for coordinated migration during repair of
      an endothelial wound.

PMID- 11294889
TI  - Mitochondrial single-stranded DNA-binding protein is required for mitochondrial
      DNA replication and development in Drosophila melanogaster.
AB  - The discovery that several inherited human diseases are caused by mtDNA depletion
      has led to an increased interest in the replication and maintenance of mtDNA. We
      have isolated a new mutant in the lopo (low power) gene from Drosophila
      melanogaster affecting the mitochondrial single-stranded DNA-binding protein
      (mtSSB), which is one of the key components in mtDNA replication and maintenance.
      lopo(1) mutants die late in the third instar before completion of metamorphosis
      because of a failure in cell proliferation. Molecular, histochemical, and
      physiological experiments show a drastic decrease in mtDNA content that is
      coupled with the loss of respiration in these mutants. However, the number and
      morphology of mitochondria are not greatly affected. Immunocytochemical analysis
      shows that mtSSB is expressed in all tissues but is highly enriched in
      proliferating tissues and in the developing oocyte. lopo(1) is the first mtSSB
      mutant in higher eukaryotes, and its analysis demonstrates the essential function
      of this gene in development, providing an excellent model to study mitochondrial
      biogenesis in animals.

PMID- 11294891
TI  - RAC1 regulates adherens junctions through endocytosis of E-cadherin.
AB  - The establishment of cadherin-dependent cell-cell contacts in human epidermal
      keratinocytes are known to be regulated by the Rac1 small GTP-binding protein,
      although the mechanisms by which Rac1 participates in the assembly or disruption
      of cell-cell adhesion are not well understood. In this study we utilized green
      fluorescent protein (GFP)-tagged Rac1 expression vectors to examine the
      subcellular distribution of Rac1 and its effects on E-cadherin-mediated cell-cell
      adhesion. Microinjection of keratinocytes with constitutively active Rac1
      resulted in cell spreading and disruption of cell-cell contacts. The ability of
      Rac1 to disrupt cell-cell adhesion was dependent on colony size, with large
      established colonies being resistant to the effects of active Rac1. Disruption of
      cell-cell contacts in small preconfluent colonies was achieved through the
      selective recruitment of E-cadherin-catenin complexes to the perimeter of
      multiple large intracellular vesicles, which were bounded by GFP-tagged L61Rac1.
      Similar vesicles were observed in noninjected keratinocytes when cell-cell
      adhesion was disrupted by removal of extracellular calcium or with the use of an
      E-cadherin blocking antibody. Moreover, formation of these structures in
      noninjected keratinocytes was dependent on endogenous Rac1 activity. Expression
      of GFP-tagged effector mutants of Rac1 in keratinocytes demonstrated that
      reorganization of the actin cytoskeleton was important for vesicle formation.
      Characterization of these Rac1-induced vesicles revealed that they were endosomal
      in nature and tightly colocalized with the transferrin receptor, a marker for
      recycling endosomes. Expression of GFP-L61Rac1 inhibited uptake of transferrin
      biotin, suggesting that the endocytosis of E-cadherin was a clathrin-independent
      mechanism. This was supported by the observation that caveolin, but not clathrin,
      localized around these structures. Furthermore, an inhibitory form of dynamin,
      known to inhibit internalization of caveolae, inhibited formation of cadherin
      vesicles. Our data suggest that Rac1 regulates adherens junctions via clathrin
      independent endocytosis of E-cadherin.

PMID- 11294892
TI  - Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity
      ratios that determine carcinoma cell proliferation or dormancy in vivo.
AB  - We discovered that a shift between the state of tumorigenicity and dormancy in
      human carcinoma (HEp3) is attained through regulation of the balance between two
      classical mitogen-activated protein kinase (MAPK)-signaling pathways, the
      mitogenic extracellular regulated kinase (ERK) and the apoptotic/growth
      suppressive stress-activated protein kinase 2 (p38(MAPK)), and that urokinase
      plasminogen activator receptor (uPAR) is an important regulator of these events.
      This is a novel function for uPAR whereby, when expressed at high level, it
      enters into frequent, activating interactions with the alpha5beta1-integrin,
      which facilitates the formation of insoluble fibronectin (FN) fibrils. Activation
      of alpha5beta1-integrin by uPAR generates persistently high level of active ERK
      necessary for tumor growth in vivo. Our results show that ERK activation is
      generated through a convergence of two pathways: a positive signal through uPAR
      activated alpha5beta1, which activates ERK, and a signal generated by the
      presence of FN fibrils that suppresses p38 activity. When fibrils are removed or
      their assembly is blocked, p38 activity increases. Low uPAR derivatives of HEp3
      cells, which are growth arrested (dormant) in vivo, have a high p38/ERK activity
      ratio, but in spite of a similar level of alpha5beta1-integrin, they do not
      assemble FN fibrils. However, when p38 activity is inhibited by pharmacological
      (SB203580) or genetic (dominant negative-p38) approaches, their ERK becomes
      activated, uPAR is overexpressed, alpha5beta1-integrins are activated, and
      dormancy is interrupted. Restoration of these properties in dormant cells can be
      mimicked by a direct re-expression of uPAR through transfection with a uPAR
      coding plasmid. We conclude that overexpression of uPAR and its interaction with
      the integrin are responsible for generating two feedback loops; one increases the
      ERK activity that feeds back by increasing the expression of uPAR. The second
      loop, through the presence of FN fibrils, suppresses p38 activity, further
      increasing ERK activity. Together these results indicate that uPAR and its
      interaction with the integrin should be considered important targets for
      induction of tumor dormancy.

PMID- 11294893
TI  - A transmembrane form of the prion protein contains an uncleaved signal peptide
      and is retained in the endoplasmic Reticulum.
AB  - Although there is considerable evidence that PrP(Sc) is the infectious form of
      the prion protein, it has recently been proposed that a transmembrane variant
      called (Ctm)PrP is the direct cause of prion-associated neurodegeneration. We
      report here, using a mutant form of PrP that is synthesized exclusively with the
      (Ctm)PrP topology, that (Ctm)PrP is retained in the endoplasmic reticulum and is
      degraded by the proteasome. We also demonstrate that (Ctm)PrP contains an
      uncleaved, N-terminal signal peptide as well as a C-terminal glycolipid anchor.
      These results provide insight into general mechanisms that control the topology
      of membrane proteins during their synthesis in the endoplasmic reticulum, and
      they also suggest possible cellular pathways by which (Ctm)PrP may cause disease.

PMID- 11294894
TI  - Layilin, a novel integral membrane protein, is a hyaluronan receptor.
AB  - The actin cytoskeleton plays a significant role in changes of cell shape and
      motility, and interactions between the actin filaments and the cell membrane are
      crucial for a variety of cellular processes. Several adaptor proteins, including
      talin, maintain the cytoskeleton-membrane linkage by binding to integral membrane
      proteins and to the cytoskeleton. Layilin, a recently characterized transmembrane
      protein with homology to C-type lectins, is a membrane-binding site for talin in
      peripheral ruffles of spreading cells. To facilitate studies of layilin's
      function, we have generated a layilin-Fc fusion protein comprising the
      extracellular part of layilin joined to human immunoglobulin G heavy chain and
      used this chimera to identify layilin ligands. Here, we demonstrate that layilin
      Fc fusion protein binds to hyaluronan immobilized to Sepharose. Microtiter plate
      binding assays, coprecipitation experiments, and staining of sections predigested
      with different glycosaminoglycan-degrading enzymes and cell adhesion assays all
      revealed that layilin binds specifically to hyaluronan but not to other tested
      glycosaminoglycans. Layilin's ability to bind hyaluronan, a ubiquitous
      extracellular matrix component, reveals an interesting parallel between layilin
      and CD44, because both can bind to cytoskeleton-membrane linker proteins through
      their cytoplasmic domains and to hyaluronan through their extracellular domains.
      This parallelism suggests a role for layilin in cell adhesion and motility.

PMID- 11294895
TI  - The Schizosaccharomyces pombe spo20(+) gene encoding a homologue of Saccharomyces
      cerevisiae Sec14 plays an important role in forespore membrane formation.
AB  - The Schizosaccharomyces pombe spo20-KC104 mutation was originally isolated in a
      screen for sporulation-deficient mutants, and the spo20-KC104 mutant exhibits
      temperature-sensitive growth. Herein, we report that S. pombe, spo20(+) is
      essential for fission yeast cell viability and is constitutively expressed
      throughout the life cycle. We also demonstrate that the spo20(+) gene product is
      structurally homologous to Saccharomyces cerevisiae Sec14, the major
      phosphatidylinositol transfer protein of budding yeast. This structural homology
      translates to a significant degree of functional relatedness because reciprocal
      complementation experiments demonstrate that each protein is able to fulfill the
      essential function of the other. Moreover, biochemical experiments show that,
      like Sec14, Spo20 is a phosphatidylinositol/phosphatidylcholine-transfer protein.
      That Spo20 is required for Golgi secretory function in vegetative cells is
      indicated by our demonstration that the spo20-KC104 mutant accumulates aberrant
      Golgi cisternae at restrictive temperatures. However, a second phenotype observed
      in Spo20-deficient fission yeast is arrest of cell division before completion of
      cell separation. Consistent with a direct role for Spo20 in controlling cell
      septation in vegetatively growing cells, localization experiments reveal that
      Spo20 preferentially localizes to the cell poles and to sites of septation of
      fission yeast cells. We also report that, when fission yeasts are challenged with
      nitrogen starvation, Spo20 translocates to the nucleus. This nuclear localization
      persists during conjugation and meiosis. On completion of meiosis, Spo20
      translocates to forespore membranes, and it is the assembly of forespore
      membranes that is abnormal in spo20-KC104 cells. In such mutants, a considerable
      fraction of forming prespores fail to encapsulate the haploid nucleus. Our
      results indicate that Spo20 regulates the formation of specialized membrane
      structures in addition to its recognized role in regulating Golgi secretory
      function.

PMID- 11294896
TI  - Distinct modes of macrophage recognition for apoptotic and necrotic cells are not
      specified exclusively by phosphatidylserine exposure.
AB  - The distinction between physiological (apoptotic) and pathological (necrotic)
      cell deaths reflects mechanistic differences in cellular disintegration and is of
      functional significance with respect to the outcomes that are triggered by the
      cell corpses. Mechanistically, apoptotic cells die via an active and ordered
      pathway; necrotic deaths, conversely, are chaotic and passive. Macrophages and
      other phagocytic cells recognize and engulf these dead cells. This clearance is
      believed to reveal an innate immunity, associated with inflammation in cases of
      pathological but not physiological cell deaths. Using objective and quantitative
      measures to assess these processes, we find that macrophages bind and engulf
      native apoptotic and necrotic cells to similar extents and with similar kinetics.
      However, recognition of these two classes of dying cells occurs via distinct and
      noncompeting mechanisms. Phosphatidylserine, which is externalized on both
      apoptotic and necrotic cells, is not a specific ligand for the recognition of
      either one. The distinct modes of recognition for these different corpses are
      linked to opposing responses from engulfing macrophages. Necrotic cells, when
      recognized, enhance proinflammatory responses of activated macrophages, although
      they are not sufficient to trigger macrophage activation. In marked contrast,
      apoptotic cells profoundly inhibit phlogistic macrophage responses; this
      represents a cell-associated, dominant-acting anti-inflammatory signaling
      activity acquired posttranslationally during the process of physiological cell
      death.

PMID- 11294897
TI  - Identification of tyrosine residues in constitutively activated fibroblast growth
      factor receptor 3 involved in mitogenesis, Stat activation, and
      phosphatidylinositol 3-kinase activation.
AB  - Fibroblast growth factor receptor 3 (FGFR3) mutations are frequently involved in
      human developmental disorders and cancer. Activation of FGFR3, through mutation
      or ligand stimulation, results in autophosphorylation of multiple tyrosine
      residues within the intracellular domain. To assess the importance of the six
      conserved tyrosine residues within the intracellular domain of FGFR3 for
      signaling, derivatives were constructed containing an N-terminal myristylation
      signal for plasma membrane localization and a point mutation (K650E) that confers
      constitutive kinase activation. A derivative containing all conserved tyrosine
      residues stimulates cellular transformation and activation of several FGFR3
      signaling pathways. Substitution of all nonactivation loop tyrosine residues with
      phenylalanine rendered this FGFR3 construct inactive, despite the presence of the
      activating K650E mutation. Addition of a single tyrosine residue, Y724, restored
      its ability to stimulate cellular transformation, phosphatidylinositol 3-kinase
      activation, and phosphorylation of Shp2, MAPK, Stat1, and Stat3. These results
      demonstrate a critical role for Y724 in the activation of multiple signaling
      pathways by constitutively activated mutants of FGFR3.

PMID- 11294898
TI  - Intracellular localization of phospholipase D1 in mammalian cells.
AB  - Phospholipase D (PLD) hydrolyzes phosphatidylcholine to generate phosphatidic
      acid. In mammalian cells this reaction has been implicated in the recruitment of
      coatomer to Golgi membranes and release of nascent secretory vesicles from the
      trans-Golgi network. These observations suggest that PLD is associated with the
      Golgi complex; however, to date, because of its low abundance, the intracellular
      localization of PLD has been characterized only indirectly through overexpression
      of chimeric proteins. We have used highly sensitive antibodies to PLD1 together
      with immunofluorescence and immunogold electron microscopy as well as cell
      fractionation to identify the intracellular localization of endogenous PLD1 in
      several cell types. Although PLD1 had a diffuse staining pattern, it was enriched
      significantly in the Golgi apparatus and was also present in cell nuclei. On
      fragmentation of the Golgi apparatus by treatment with nocodazole, PLD1 closely
      associated with membrane fragments, whereas after inhibition of PA synthesis,
      PLD1 dissociated from the membranes. Overexpression of an hemagglutinin-tagged
      form of PLD1 resulted in displacement of the endogenous enzyme from its
      perinuclear localization to large vesicular structures. Surprisingly, when the
      Golgi apparatus collapsed in response to brefeldin A, the nuclear localization of
      PLD1 was enhanced significantly. Our data show that the intracellular
      localization of PLD1 is consistent with a role in vesicle trafficking from the
      Golgi apparatus and suggest that it also functions in the cell nucleus.

PMID- 11294899
TI  - Deletion of yeast p24 genes activates the unfolded protein response.
AB  - Yeast cells lacking a functional p24 complex accumulate a subset of secretory
      proteins in the endoplasmic reticulum (ER) and increase the extracellular
      secretion of HDEL-containing ER residents such as Kar2p/BiP. We report that a
      loss of p24 function causes activation of the unfolded protein response (UPR) and
      leads to increased KAR2 expression. The HDEL receptor (Erd2p) is functional and
      traffics in p24 deletion strains as in wild-type strains, however the capacity of
      the retrieval pathway is exceeded. Other conditions that activate the UPR and
      elevate KAR2 expression also lead to extracellular secretion of Kar2p. Using an
      in vitro assay that reconstitutes budding from the ER, we detect elevated levels
      of Kar2p in ER-derived vesicles from p24 deletion strains and from wild-type
      strains with an activated UPR. Silencing the UPR by IRE1 deletion diminished
      Kar2p secretion under these conditions. We suggest that activation of the UPR
      plays a major role in extracellular secretion of Kar2p.

PMID- 11294900
TI  - Cell cycle-dependent changes in microtubule dynamics in living cells expressing
      green fluorescent protein-alpha tubulin.
AB  - LLCPK-1 cells were transfected with a green fluorescent protein (GFP)-alpha
      tubulin construct and a cell line permanently expressing GFP-alpha tubulin was
      established (LLCPK-1alpha). The mitotic index and doubling time for LLCPK-1alpha
      were not significantly different from parental cells. Quantitative immunoblotting
      showed that 17% of the tubulin in LLCPK-1alpha cells was GFP-tubulin; the level
      of unlabeled tubulin was reduced to 82% of that in parental cells. The parameters
      of microtubule dynamic instability were compared for interphase LLCPK-1alpha and
      parental cells injected with rhodamine-labeled tubulin. Dynamic instability was
      very similar in the two cases, demonstrating that LLCPK-1alpha cells are a useful
      tool for analysis of microtubule dynamics throughout the cell cycle. Comparison
      of astral microtubule behavior in mitosis with microtubule behavior in interphase
      demonstrated that the frequency of catastrophe increased twofold and that the
      frequency of rescue decreased nearly fourfold in mitotic compared with interphase
      cells. The percentage of time that microtubules spent in an attenuated state, or
      pause, was also dramatically reduced, from 73.5% in interphase to 11.4% in
      mitosis. The rates of microtubule elongation and rapid shortening were not
      changed; overall dynamicity increased 3.6-fold in mitosis. Microtubule release
      from the centrosome and a subset of differentially stable astral microtubules
      were also observed. The results provide the first quantitative measurements of
      mitotic microtubule dynamics in mammalian cells.

PMID- 11294901
TI  - Identification of discrete classes of endosome-derived small vesicles as a major
      cellular pool for recycling membrane proteins.
AB  - Vesicles carrying recycling plasma membrane proteins from early endosomes have
      not yet been characterized. Using Chinese hamster ovary cells transfected with
      the facilitative glucose transporter, GLUT4, we identified two classes of
      discrete, yet similarly sized, small vesicles that are derived from early
      endosomes. We refer to these postendosomal vesicles as endocytic small vesicles
      or ESVs. One class of ESVs contains a sizable fraction of the pool of the
      transferrin receptor, and the other contains 40% of the total cellular pool of
      GLUT4 and is enriched in the insulin-responsive aminopeptidase (IRAP). The ESVs
      contain cellubrevin and Rab4 but are lacking other early endosomal markers, such
      as EEA1 or syntaxin13. The ATP-, temperature-, and cytosol-dependent formation of
      ESVs has been reconstituted in vitro from endosomal membranes. Guanosine 5'
      [gamma-thio]triphosphate and neomycin, but not brefeldin A, inhibit budding of
      the ESVs in vitro. A monoclonal antibody recognizing the GLUT4 cytoplasmic tail
      perturbs the in vitro targeting of GLUT4 to the ESVs without interfering with the
      incorporation of IRAP or TfR. We suggest that cytosolic proteins mediate the
      incorporation of recycling membrane proteins into discrete populations of ESVs
      that serve as carrier vesicles to store and then transport the cargo from early
      endosomes, either directly or indirectly, to the cell surface.

PMID- 11294903
TI  - Nonsense-mediated decay of mRNA for the selenoprotein phospholipid hydroperoxide
      glutathione peroxidase is detectable in cultured cells but masked or inhibited in
      rat tissues.
AB  - Previous studies of mRNA for classical glutathione peroxidase 1 (GPx1)
      demonstrated that hepatocytes of rats fed a selenium-deficient diet have less
      cytoplasmic GPx1 mRNA than hepatocytes of rats fed a selenium-adequate diet. This
      is because GPx1 mRNA is degraded by the surveillance pathway called nonsense
      mediated mRNA decay (NMD) when the selenocysteine codon is recognized as
      nonsense. Here, we examine the mechanism by which the abundance of phospholipid
      hydroperoxide glutathione peroxidase (PHGPx) mRNA, another selenocysteine
      encoding mRNA, fails to decrease in the hepatocytes and testicular cells of rats
      fed a selenium-deficient diet. We demonstrate with cultured NIH3T3 fibroblasts or
      H35 hepatocytes transiently transfected with PHGPx gene variants under selenium
      supplemented or selenium-deficient conditions that PHGPx mRNA is, in fact, a
      substrate for NMD when the selenocysteine codon is recognized as nonsense. We
      also demonstrate that the endogenous PHGPx mRNA of untransfected H35 cells is
      subject to NMD. The failure of previous reports to detect the NMD of PHGPx mRNA
      in cultured cells is likely attributable to the expression of PHGPx cDNA rather
      than the PHGPx gene. We conclude that 1) the sequence of the PHGPx gene is
      adequate to support the NMD of product mRNA, and 2) there is a mechanism in liver
      and testis but not cultured fibroblasts and hepatocytes that precludes or masks
      the NMD of PHGPx mRNA.

PMID- 11294902
TI  - Roles of phosphatidylethanolamine and of its several biosynthetic pathways in
      Saccharomyces cerevisiae.
AB  - Three different pathways lead to the synthesis of phosphatidylethanolamine
      (PtdEtn) in yeast, one of which is localized to the inner mitochondrial membrane.
      To study the contribution of each of these pathways, we constructed a series of
      deletion mutants in which different combinations of the pathways are blocked.
      Analysis of their growth phenotypes revealed that a minimal level of PtdEtn is
      essential for growth. On fermentable carbon sources such as glucose, endogenous
      ethanolaminephosphate provided by sphingolipid catabolism is sufficient to allow
      synthesis of the essential amount of PtdEtn through the cytidyldiphosphate (CDP)
      ethanolamine pathway. On nonfermentable carbon sources, however, a higher level
      of PtdEtn is required for growth, and the amounts of PtdEtn produced through the
      CDP-ethanolamine pathway and by extramitochondrial phosphatidylserine
      decarboxylase 2 are not sufficient to maintain growth unless the action of the
      former pathway is enhanced by supplementing the growth medium with ethanolamine.
      Thus, in the absence of such supplementation, production of PtdEtn by
      mitochondrial phosphatidylserine decarboxylase 1 becomes essential. In psd1Delta
      strains or cho1Delta strains (defective in phosphatidylserine synthesis), which
      contain decreased amounts of PtdEtn, the growth rate on nonfermentable carbon
      sources correlates with the content of PtdEtn in mitochondria, suggesting that
      import of PtdEtn into this organelle becomes growth limiting. Although
      morphological and biochemical analysis revealed no obvious defects of PtdEtn
      depleted mitochondria, the mutants exhibited an enhanced formation of respiration
      deficient cells. Synthesis of glycosylphosphatidylinositol-anchored proteins is
      also impaired in PtdEtn-depleted cells, as demonstrated by delayed maturation of
      Gas1p. Carboxypeptidase Y and invertase, on the other hand, were processed with
      wild-type kinetics. Thus, PtdEtn depletion does not affect protein secretion in
      general, suggesting that high levels of nonbilayer-forming lipids such as PtdEtn
      are not essential for membrane vesicle fusion processes in vivo.

PMID- 11294904
TI  - Endothelial transcytotic machinery involves supramolecular protein-lipid
      complexes.
AB  - We have demonstrated that the plasmalemmal vesicles (caveolae) of the continuous
      microvascular endothelium function as transcytotic vesicular carriers for protein
      molecules > 20 A and that transcytosis is an N-ethylmaleimide-sensitive factor
      (NSF)-dependent, N-ethylmaleimide-sensitive process. We have further investigated
      NSF interactions with endothelial proteins to find out 1) whether a complete set
      of fusion and targeting proteins is present in the endothelium; 2) whether they
      are organized in multimolecular complexes as in neurons; and 3) whether the
      endothelial multimolecular complexes differ from their neuronal counterparts,
      because of their specialized role in transcytosis. To generate the complexes, we
      have used myc-NSF, cultured pulmonary endothelial cells, and rat lung cytosol and
      membrane preparations; to detect them we have applied coimmunoprecipitation with
      myc antibodies; and to characterize them we have used velocity sedimentation and
      cross-linking procedures. We have found that both cytosolic and membrane
      fractions contain complexes that comprise beside soluble NSF attachment proteins
      and SNAREs (soluble NSF attachment protein receptor), rab 5, dynamin, caveolin,
      and lipids. By immunogold labeling and negative staining we have detected in
      these complexes, myc-NSF, syntaxin, dynamin, caveolin, and endogenous NSF.
      Similar complexes are formed by endogenous NSF. The results indicate that
      complexes with a distinct protein-lipid composition exist and suggest that they
      participate in targeting, fusion, and fission of caveolae with the endothelial
      plasmalemma.

PMID- 11294905
TI  - The ADP ribosylation factor-nucleotide exchange factors Gea1p and Gea2p have
      overlapping, but not redundant functions in retrograde transport from the Golgi
      to the endoplasmic reticulum.
AB  - The activation of the small ras-like GTPase Arf1p requires the action of guanine
      nucleotide exchange factors. Four Arf1p guanine nucleotide exchange factors have
      been identified in yeast: Sec7p, Syt1p, Gea1p, and its homologue Gea2p. We
      identified GEA2 as a multicopy suppressor of a sec21-3 temperature-sensitive
      mutant. SEC21 encodes the gamma-subunit of coatomer, a heptameric protein complex
      that together with Arf1p forms the COPI coat. GEA1 and GEA2 have at least
      partially overlapping functions, because deletion of either gene results in no
      obvious phenotype, whereas the double null mutant is inviable. Conditional
      mutants defective in both GEA1 and GEA2 accumulate endoplasmic reticulum and
      Golgi membranes under restrictive conditions. The two genes do not serve
      completely overlapping functions because a Deltagea1 Deltaarf1 mutant is not more
      sickly than a Deltaarf1 strain, whereas Deltagea2 Deltaarf1 is inviable.
      Biochemical experiments revealed similar distributions and activities for the two
      proteins. Gea1p and Gea2p exist both in membrane-bound and in soluble forms. The
      membrane-bound forms, at least one of which, Gea2p, can be visualized on Golgi
      structures, are both required for vesicle budding and protein transport from the
      Golgi to the endoplasmic reticulum. In contrast, Sec7p, which is required for
      protein transport within the Golgi, is not required for retrograde protein
      trafficking.

PMID- 11294906
TI  - Uptake of the ATP-binding cassette (ABC) transporter Ste6 into the yeast vacuole
      is blocked in the doa4 Mutant.
AB  - Previous experiments suggested that trafficking of the a-factor transporter Ste6
      of Saccharomyces cerevisiae to the yeast vacuole is regulated by ubiquitination.
      To define the ubiquitination-dependent step in the trafficking pathway, we
      examined the intracellular localization of Ste6 in the ubiquitination-deficient
      doa4 mutant by immunofluorescence experiments, with a Ste6-green fluorescent
      protein fusion protein and by sucrose density gradient fractionation. We found
      that Ste6 accumulated at the vacuolar membrane in the doa4 mutant and not at the
      cell surface. Experiments with a doa4 pep4 double mutant showed that Ste6 uptake
      into the lumen of the vacuole is inhibited in the doa4 mutant. The uptake defect
      could be suppressed by expression of additional ubiquitin, indicating that it is
      primarily the result of a lowered ubiquitin level (and thus of reduced
      ubiquitination) and not the result of a deubiquitination defect. Based on our
      findings, we propose that ubiquitination of Ste6 or of a trafficking factor is
      required for Ste6 sorting into the multivesicular bodies pathway. In addition, we
      obtained evidence suggesting that Ste6 recycles between an internal compartment
      and the plasma membrane.

PMID- 11294908
TI  - Transforming growth factor-beta induces nuclear import of Smad3 in an importin
      beta1 and Ran-dependent manner.
AB  - Smad proteins are cytoplasmic signaling effectors of transforming growth factor
      beta (TGF-beta) family cytokines and regulate gene transcription in the nucleus.
      Receptor-activated Smads (R-Smads) become phosphorylated by the TGF-beta type I
      receptor. Rapid and precise transport of R-Smads to the nucleus is of crucial
      importance for signal transduction. By focusing on the R-Smad Smad3 we
      demonstrate that 1) only activated Smad3 efficiently enters the nucleus of
      permeabilized cells in an energy- and cytosol-dependent manner. 2) Smad3, via its
      N-terminal domain, interacts specifically with importin-beta1 and only after
      activation by receptor. In contrast, the unique insert of exon3 in the N-terminal
      domain of Smad2 prevents its association with importin-beta1. 3) Nuclear import
      of Smad3 in vivo requires the action of the Ran GTPase, which mediates release of
      Smad3 from the complex with importin-beta1. 4) Importin-beta1, Ran, and p10/NTF2
      are sufficient to mediate import of activated Smad3. The data describe a pathway
      whereby Smad3 phosphorylation by the TGF-beta receptor leads to enhanced
      interaction with importin-beta1 and Ran-dependent import and release into the
      nucleus. The import mechanism of Smad3 shows distinct features from that of the
      related Smad2 and the structural basis for this difference maps to the divergent
      sequences of their N-terminal domains.

PMID- 11294907
TI  - Roles of a fimbrin and an alpha-actinin-like protein in fission yeast cell
      polarization and cytokinesis.
AB  - Eukaryotic cells contain many actin-interacting proteins, including the alpha
      actinins and the fimbrins, both of which have actin cross-linking activity in
      vitro. We report here the identification and characterization of both an alpha
      actinin-like protein (Ain1p) and a fimbrin (Fim1p) in the fission yeast
      Schizosaccharomyces pombe. Ain1p localizes to the actomyosin-containing medial
      ring in an F-actin-dependent manner, and the Ain1p ring contracts during
      cytokinesis. ain1 deletion cells have no obvious defects under normal growth
      conditions but display severe cytokinesis defects, associated with defects in
      medial-ring and septum formation, under certain stress conditions. Overexpression
      of Ain1p also causes cytokinesis defects, and the ain1 deletion shows synthetic
      effects with other mutations known to affect medial-ring positioning and/or
      organization. Fim1p localizes both to the cortical actin patches and to the
      medial ring in an F-actin-dependent manner, and several lines of evidence suggest
      that Fim1p is involved in polarization of the actin cytoskeleton. Although a fim1
      deletion strain has no detectable defect in cytokinesis, overexpression of Fim1p
      causes a lethal cytokinesis defect associated with a failure to form the medial
      ring and concentrate actin patches at the cell middle. Moreover, an ain1 fim1
      double mutant has a synthetical-lethal defect in medial-ring assembly and cell
      division. Thus, Ain1p and Fim1p appear to have an overlapping and essential
      function in fission yeast cytokinesis. In addition, protein-localization and
      mutant-phenotype data suggest that Fim1p, but not Ain1p, plays important roles in
      mating and in spore formation.

PMID- 11294909
TI  - O-mannosylation protects mutant alpha-factor precursor from endoplasmic reticulum
      associated degradation.
AB  - Secretory proteins that fail to fold in the endoplasmic reticulum (ER) are
      transported back to the cytosol and degraded by proteasomes. It remains unclear
      how the cell distinguishes between folding intermediates and misfolded proteins.
      We asked whether misfolded secretory proteins are covalently modified in the ER
      before export. We found that a fraction of mutant alpha-factor precursor, but not
      the wild type, was progressively O-mannosylated in microsomes and in intact yeast
      cells by protein O-mannosyl transferase 2 (Pmt2p). O-Mannosylation increased
      significantly in vitro under ER export conditions, i.e., in the presence of ATP
      and cytosol, and this required export-proficient Sec61p in the ER membrane.
      Deletion of PMT2, however, did not abrogate mutant alpha-factor precursor
      degradation but, rather, enhanced its turnover in intact yeast cells. In vitro, O
      mannosylated mutant alpha-factor precursor was stable and protease protected, and
      a fraction was associated with Sec61p in the ER lumen. Thus, prolonged ER
      residence allows modification of exposed O-mannosyl acceptor sites in misfolded
      proteins, which abrogates misfolded protein export from the ER at a posttargeting
      stage. We conclude that there is a limited window of time during which misfolded
      proteins can be removed from the ER before they acquire inappropriate
      modifications that can interfere with disposal through the Sec61 channel.

PMID- 11294910
TI  - Changes in organization of the endoplasmic reticulum during Xenopus oocyte
      maturation and activation.
AB  - The organization of the endoplasmic reticulum (ER) in the cortex of Xenopus
      oocytes was investigated during maturation and activation using a green
      fluorescent protein chimera, immunofluorescence, and electron microscopy. Dense
      clusters of ER developed on the vegetal side (the side opposite the meiotic
      spindle) during maturation. Small clusters appeared transiently at the time of
      nuclear envelope breakdown, disappeared at the time of first polar body
      formation, and then reappeared as larger clusters in mature eggs. The appearance
      of the large ER clusters was correlated with an increase in releasability of
      Ca(2+) by IP(3). The clusters dispersed during the Ca(2+) wave at activation.
      Possible relationships of ER structure and Ca(2+) regulation are discussed.

PMID- 11294911
TI  - Evidence for an intrinsic toxicity of phosphatidylcholine to Sec14p-dependent
      protein transport from the yeast Golgi complex.
AB  - Yeast phosphatidylinositol-transfer protein (Sec14p) is essential for Golgi
      secretory function and cell viability. This requirement of Sec14p is relieved by
      genetic inactivation of the cytidine diphosphate-choline pathway for
      phosphatidycholine (PtdCho) biosynthesis. Standard phenotypic analyses indicate
      that inactivation of the phosphatidylethanolamine (PtdEtn) pathway for PtdCho
      biosynthesis, however, does not rescue the growth and secretory defects
      associated with Sec14p deficiency. We now report inhibition of choline uptake
      from the media reveals an efficient "bypass Sec14p" phenotype associated with
      PtdEtn-methylation pathway defects. We further show that the bypass Sec14p
      phenotype associated with PtdEtn-methylation pathway defects resembles other
      bypass Sec14p mutations in its dependence on phospholipase D activity. Finally,
      we find that increased dosage of enzymes that catalyze phospholipase D
      independent turnover of PtdCho, via mechanisms that do not result in a direct
      production of phosphatidic acid or diacylglycerol, effect a partial rescue of
      sec14-1(ts)-associated growth defects. Taken together, these data support the
      idea that PtdCho is intrinsically toxic to yeast Golgi secretory function.

PMID- 11294912
TI  - Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its
      role in integrin-mediated actin reorganization and focal adhesion formation.
AB  - Testicular protein kinase 1 (TESK1) is a serine/threonine kinase with a structure
      composed of a kinase domain related to those of LIM-kinases and a unique C
      terminal proline-rich domain. Like LIM-kinases, TESK1 phosphorylated cofilin
      specifically at Ser-3, both in vitro and in vivo. When expressed in HeLa cells,
      TESK1 stimulated the formation of actin stress fibers and focal adhesions. In
      contrast to LIM-kinases, the kinase activity of TESK1 was not enhanced by Rho
      associated kinase (ROCK) or p21-activated kinase, indicating that TESK1 is not
      their downstream effector. Both the kinase activity of TESK1 and the level of
      cofilin phosphorylation increased by plating cells on fibronectin. Y-27632, a
      specific inhibitor of ROCK, inhibited LIM-kinase-induced cofilin phosphorylation
      but did not affect fibronectin-induced or TESK1-induced cofilin phosphorylation
      in HeLa cells. Expression of a kinase-negative TESK1 suppressed cofilin
      phosphorylation and formation of stress fibers and focal adhesions induced in
      cells plated on fibronectin. These results suggest that TESK1 functions
      downstream of integrins and plays a key role in integrin-mediated actin
      reorganization, presumably through phosphorylating and inactivating cofilin. We
      propose that TESK1 and LIM-kinases commonly phosphorylate cofilin but are
      regulated in different ways and play distinct roles in actin reorganization in
      living cells.

PMID- 11294913
TI  - Depletion of acyl-coenzyme A-binding protein affects sphingolipid synthesis and
      causes vesicle accumulation and membrane defects in Saccharomyces cerevisiae.
AB  - Deletion of the yeast gene ACB1 encoding Acb1p, the yeast homologue of the acyl
      CoA-binding protein (ACBP), resulted in a slower growing phenotype that adapted
      into a faster growing phenotype with a frequency >1:10(5). A conditional knockout
      strain (Y700pGAL1-ACB1) with the ACB1 gene under control of the GAL1 promoter
      exhibited an altered acyl-CoA profile with a threefold increase in the relative
      content of C18:0-CoA, without affecting total acyl-CoA level as previously
      reported for an adapted acb1Delta strain. Depletion of Acb1p did not affect the
      general phospholipid pattern, the rate of phospholipid synthesis, or the turnover
      of individual phospholipid classes, indicating that Acb1p is not required for
      general glycerolipid synthesis. In contrast, cells depleted for Acb1p showed a
      dramatically reduced content of C26:0 in total fatty acids and the sphingolipid
      synthesis was reduced by 50-70%. The reduced incorporation of [(3)H]myo-inositol
      into sphingolipids was due to a reduced incorporation into inositol
      phosphoceramide and mannose-inositol-phosphoceramide only, a pattern that is
      characteristic for cells with aberrant endoplasmic reticulum to Golgi transport.
      The plasma membrane of the Acb1p-depleted strain contained increased levels of
      inositol-phosphoceramide and mannose-inositol-phosphoceramide and
      lysophospholipids. Acb1p-depleted cells accumulated 50- to 60-nm vesicles and
      autophagocytotic like bodies and showed strongly perturbed plasma membrane
      structures. The present results strongly suggest that Acb1p plays an important
      role in fatty acid elongation and membrane assembly and organization.

PMID- 11294914
TI  - Profilin binding to poly-L-proline and actin monomers along with ability to
      catalyze actin nucleotide exchange is required for viability of fission yeast.
AB  - We tested the ability of 87 profilin point mutations to complement temperature
      sensitive and null mutations of the single profilin gene of the fission yeast
      Schizosaccharomyces pombe. We compared the biochemical properties of 13 stable
      noncomplementing profilins with an equal number of complementing profilin
      mutants. A large quantitative database revealed the following: 1) in a profilin
      null background fission yeast grow normally with profilin mutations having >10%
      of wild-type affinity for actin or poly-L-proline, but lower affinity for either
      ligand is incompatible with life; 2) in the cdc3-124 profilin ts background,
      fission yeast function with profilin having only 2-5% wild-type affinity for
      actin or poly-L-proline; and 3) special mutations show that the ability of
      profilin to catalyze nucleotide exchange by actin is an essential function. Thus,
      poly-L-proline binding, actin binding, and actin nucleotide exchange are each
      independent requirements for profilin function in fission yeast.

PMID- 11294916
TI  - ALS defeats gabapentin: reflections on another failed treatment.

PMID- 11294915
TI  - Cadherin sequences that inhibit beta-catenin signaling: a study in yeast and
      mammalian cells.
AB  - Drosophila Armadillo and its mammalian homologue beta-catenin are scaffolding
      proteins involved in the assembly of multiprotein complexes with diverse
      biological roles. They mediate adherens junction assembly, thus determining
      tissue architecture, and also transduce Wnt/Wingless intercellular signals, which
      regulate embryonic cell fates and, if inappropriately activated, contribute to
      tumorigenesis. To learn more about Armadillo/beta-catenin's scaffolding function,
      we examined in detail its interaction with one of its protein targets, cadherin.
      We utilized two assay systems: the yeast two-hybrid system to study cadherin
      binding in the absence of Armadillo/beta-catenin's other protein partners, and
      mammalian cells where interactions were assessed in their presence. We found that
      segments of the cadherin cytoplasmic tail as small as 23 amino acids bind
      Armadillo or beta-catenin in yeast, whereas a slightly longer region is required
      for binding in mammalian cells. We used mutagenesis to identify critical amino
      acids required for cadherin interaction with Armadillo/beta-catenin. Expression
      of such short cadherin sequences in mammalian cells did not affect adherens
      junctions but effectively inhibited beta-catenin-mediated signaling. This
      suggests that the interaction between beta-catenin and T cell factor family
      transcription factors is a sensitive target for disruption, making the use of
      analogues of these cadherin derivatives a potentially useful means to suppress
      tumor progression.

PMID- 11294917
TI  - Why do benign astrocytomas become malignant in NF1?

PMID- 11294918
TI  - Practice parameter: Steroids, acyclovir, and surgery for Bell's palsy (an
      evidence-based review): report of the Quality Standards Subcommittee of the
      American Academy of Neurology.
AB  - OBJECTIVE: To determine the effectiveness of steroids, acyclovir, and surgical
      facial nerve decompression in Bell's palsy. METHODS: The authors identified
      articles by searching MEDLINE and selected those that prospectively compared
      outcomes in patients treated with steroids, acyclovir, or surgery with patients
      not receiving these modalities. The authors graded the quality of each study
      (class I to IV) using a standard classification-of-evidence scheme. They compared
      the proportion of patients recovering facial function in the treated group to the
      proportion of patients recovering facial function in the control group. RESULTS:
      The authors identified no adequately powered class I studies for any treatment
      modality. The pooled results of two class I and two class II studies showed
      significantly better facial outcomes in steroid-treated patients compared with
      non-steroid-treated patients (relative rate good outcome 1.16, 95% CI 1.05 to
      1.29). One class II study demonstrated a significant benefit from acyclovir in
      combination with prednisone compared with prednisone alone (relative rate good
      outcome 1.22, 95% CI 1.02 to 1.45). All studies describing outcomes in patients
      treated with facial nerve decompression were graded as class IV. CONCLUSION: For
      patients with Bell's palsy, a benefit from steroids, acyclovir, or facial nerve
      decompression has not been definitively established. However, available evidence
      suggests that steroids are probably effective and acyclovir (combined with
      prednisone) is possibly effective in improving facial functional outcomes. There
      is insufficient evidence to make recommendations regarding surgical facial nerve
      decompression for Bell's palsy. Well-designed studies of the effectiveness of
      treatments for Bell's palsy are still needed.

PMID- 11294920
TI  - Familial cerebellar ataxia with muscle coenzyme Q10 deficiency.
AB  - OBJECTIVE: To describe a clinical syndrome of cerebellar ataxia associated with
      muscle coenzyme Q10 (CoQ10) deficiency. BACKGROUND: Muscle CoQ10 deficiency has
      been reported only in a few patients with a mitochondrial encephalomyopathy
      characterized by 1) recurrent myoglobinuria; 2) brain involvement (seizures,
      ataxia, mental retardation), and 3) ragged-red fibers and lipid storage in the
      muscle biopsy. METHODS: Having found decreased CoQ10 levels in muscle from a
      patient with unclassified familial cerebellar ataxia, the authors measured CoQ10
      in muscle biopsies from other patients in whom cerebellar ataxia could not be
      attributed to known genetic causes. RESULTS: The authors found muscle CoQ10
      deficiency (26 to 35% of normal) in six patients with cerebellar ataxia,
      pyramidal signs, and seizures. All six patients responded to CoQ10
      supplementation; strength increased, ataxia improved, and seizures became less
      frequent. CONCLUSIONS: Primary CoQ10 deficiency is a potentially important cause
      of familial ataxia and should be considered in the differential diagnosis of this
      condition because CoQ10 administration seems to improve the clinical picture.

PMID- 11294919
TI  - Phase III randomized trial of gabapentin in patients with amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Preclinical and clinical studies of gabapentin in patients with ALS
      led the authors to undertake a phase III randomized clinical trial. METHODS:
      Patients were randomly assigned, in a double-blinded fashion, to receive oral
      gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure
      was the average rate of decline in isometric arm muscle strength for those with
      two or more evaluations. RESULTS: Two hundred four patients enrolled, 196 had two
      or more evaluations, and 128 patients completed the study. The mean rate of
      decline of the arm muscle strength was not significantly different between the
      groups. Moreover, there was no beneficial effect upon the rate of decline of
      other secondary measures (vital capacity, survival, ALS functional rating scale,
      timed walking) nor was there any symptomatic benefit. In fact, analysis of the
      combined data from the phase II and III trials revealed a significantly more
      rapid decline of forced vital capacity in patients treated with gabapentin.
      CONCLUSION: These data provide no evidence of a beneficial effect of gabapentin
      on disease progression or symptoms in patients with ALS.

PMID- 11294921
TI  - A surface plasmon resonance biosensor assay for measurement of anti-GM(1)
      antibodies in neuropathy.
AB  - OBJECTIVE: To develop a rapid assay for the detection and measurement of anti
      GM(1) ganglioside antibodies in patients with neuropathy, using a surface plasmon
      resonance-based biosensor. BACKGROUND: Elevated levels of anti-GM(1) ganglioside
      antibodies are observed in patients with acute and chronic motor neuropathies.
      Assays for detecting anti-GM(1) antibodies in serum are increasingly being used
      to help the physician in the evaluation of these patients. METHODS: Antigens were
      immobilized by adsorption of GM(1) (active) and GM(2) (control) gangliosides onto
      a dextran-based sensor chip which is in contact with a flow cell carrying the
      sample. Interaction of specific antibodies directed against GM(1) with the
      ganglioside-coated sensor chip caused a change in refractive index at the surface
      of the chip, which was detected by an optical sensor, using the phenomenon of
      surface plasmon resonance. Sera from patients and healthy individuals were
      analyzed by the new assay and results were compared with those from ELISA. Anti
      GM(1) antibody isotype was identified by using a secondary antibody. RESULTS: The
      binding of anti-GM(1) antibodies to the immobilized GM(1) was observed in real
      time after reference subtraction of the response from GM(2) control. The response
      was proportional to antibody concentration. The assay exhibited high specificity
      for sera from patients with multifocal motor neuropathy and Guillain-Barre
      syndrome with antibodies against GM(1). CONCLUSIONS: The surface plasmon
      resonance biosensor assay offers a rapid system for directly measuring antibody
      levels in serum without the use of any labels, while comparing favorably with the
      ELISA system in sensitivity and specificity.

PMID- 11294922
TI  - Autonomic impairment in painful neuropathy.
AB  - OBJECTIVES: 1) To determine the degree and distribution and quantitate the
      severity of autonomic impairment in painful neuropathy (PN). 2) To assess the
      role of autonomic testing in evaluating PN. METHODS: The authors studied 92
      patients with PN (60 women and 32 men, age 56.9 +/- 12.4 years) using: 1)
      autonomic reflex testing (ART), Quantitative Sudomotor Axon Reflex Test (QSART),
      cardiac-vagal, head-up tilt, and surface skin temperature; 2) autonomic symptoms
      questionnaire; 3) nerve conduction (NCS) and laboratory studies; 4) quantitative
      sensory testing; 5) skin biopsy; and 6) Composite Autonomic Symptoms Score (CASS)
      scale to grade ART results from 0 (normal) to 10 (autonomic failure). RESULTS:
      Autonomic involvement in PN had characteristic features. Main symptoms were pain,
      secretory and skin vasomotor signs, hypertension, and impotence. ART results were
      abnormal in 86 (93.5%) (CASS < 4), QSART in 67 (72.8%), cardiac-vagal index in 58
      (63%), skin temperature in 51 (55.4%), orthostatic hypertension in 39 (42.3%),
      and family history of PN in 26 (21%) of patients. Group 1 (abnormal NCS) (n = 45)
      had more severe ART and sensory abnormalities than the Group 2 (normal NCS) (n =
      47): 1) CASS 2.0 +/- 0.96 vs 1.55 +/- 0.88 (p < 0.01), cardiac-vagal index (p <
      0.02), skin temperature (p < 0.02), hypertension (p < 0.03), cooling (p < 0.002),
      and vibration (p < 0.0005) thresholds. CONCLUSIONS: Autonomic symptoms in painful
      neuropathy are predominantly cholinergic and form a unique constellation of
      features that are distinct from other autonomic neuropathies.

PMID- 11294923
TI  - Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the
      candidate gene.
AB  - BACKGROUND: Tibial muscular dystrophy (TMD), a late-onset dominant distal
      myopathy, is caused by yet unknown mutations on chromosome 2q, whereas MD with
      myositis (MDM) is a muscular dystrophy of the mouse, also progressing with age
      and linked to mouse chromosome 2. For both disorders, linkage studies have
      implicated titin as a potential candidate gene. METHODS: The authors analyzed
      major candidate regions in the titin gene by sequencing and Southern blot
      hybridization, and performed titin immunohistochemistry on TMD patient material
      to identify the underlying mutation. Western blot studies were performed on the
      known titin ligands in muscle samples of both disorders and controls, and
      analysis of apoptosis was also performed. RESULTS: The authors identified almost
      complete loss of calpain3, a ligand of titin, in the patient with limb-girdle MD
      (LGMD) with a homozygous state of TMD haplotype when primary calpain3 gene defect
      was excluded. Apoptotic myonuclei with altered distribution of transcription
      factor NF-kB and its inhibitor IkBalpha were encountered in muscle samples of
      patients with either heterozygous or homozygous TMD haplotype. Similar findings
      were confirmed in the MDM mouse. CONCLUSIONS: These results imply that titin
      mutations may be responsible for TMD, and that the pathophysiologic pathway
      following calpain3 deficiency may overlap with LGMD2A. The loss of calpain3 could
      be a downstream effect of the deficient TMD gene product. The significance of the
      secondary calpain3 defect for the pathogenesis of TMD was emphasized by similar
      calpain3 deficiency in the MDM mouse, which is suggested to be a mouse model for
      TMD. Homozygous mutation at the 2q locus may thus be capable of producing yet
      another LGMD.

PMID- 11294924
TI  - A new mutation in a family with cold-aggravated myotonia disrupts Na(+) channel
      inactivation.
AB  - OBJECTIVE: To identify the molecular and physiologic abnormality in familial
      myotonia with cold sensitivity, hypertrophy, and no weakness. BACKGROUND: Sodium
      channel mutations were previously identified as the cause of several allelic
      disorders with varying combinations of myotonia and periodic paralysis. A three
      generation family with dominant myotonia aggravated by cooling, but no weakness,
      was screened for mutations in the skeletal muscle sodium channel alpha-subunit
      gene (SCN4A). METHODS: Single-strand conformation polymorphism was used to screen
      all 24 exons of SCN4A and abnormal conformers were sequenced to confirm the
      presence of mutations. The functional consequence of a SCN4A mutation was
      explored by recording sodium currents from human embryonic kidney cells
      transiently transfected with an expression construct that was mutated to
      reproduce the genetic defect. RESULTS: A three-generation Italian family with
      myotonia is presented, in which a novel SCN4A mutation (leucine 266 substituted
      by valine, L266V) is identified. This change removes only a single methylene
      group from the 1,836-amino-acid protein, and is present in a region of the
      protein previously not known to be critical for channel function (domain I
      transmembrane segment 5). Electrophysiologic studies of the L266V mutation showed
      defects in fast inactivation, consistent with other disease-causing SCN4A
      mutations studied to date. Slow inactivation was not impaired. CONCLUSIONS: This
      novel mutation of the sodium channel indicates that a single carbon change in a
      transmembrane alpha-helix of domain I can alter channel inactivation and cause
      cold-sensitive myotonia.

PMID- 11294925
TI  - Cancer-related gene expression profiles in NF1-associated pilocytic astrocytomas.
AB  - BACKGROUND: Individuals affected with neurofibromatosis 1 (NF1) develop juvenile
      pilocytic astrocytomas (JPA) at an increased frequency, suggesting that the NF1
      gene product, neurofibromin, functions as a negative growth regulator for
      astrocytes. Previously, the authors demonstrated that NF1-associated astrocytomas
      exhibit deletions and loss of NF1 gene expression on the DNA and protein levels.
      However, little is known about additional genetic events in clinically and
      radiographically progressive NF1-associated pilocytic astrocytomas.
      OBJECTIVE/METHODS: To understand the potential role of cooperating genetic events
      in the development of these low-grade tumors, the authors used
      immunohistochemistry and selected confirmatory Western blots to examine nine
      symptomatic NF1-associated pilocytic astrocytomas for gene products whose
      expression patterns are altered in fibrillary astrocytomas. RESULTS: The authors
      demonstrate that p53, p16, retinoblastoma (RB), epidermal growth factor receptor
      (EGFR), cyclin-dependent kinase 4 (CDK4), platelet-derived growth factor A (PDGF
      A) and PDGF receptor alpha (PDGF-Ralpha) protein expression profiles are not
      altered in NF1-associated pilocytic astrocytomas. Similar to their sporadic
      counterparts, NF1-associated JPA also strongly expressed PEN5, a marker of post
      O2A stage oligodendroglial precursor cells. CONCLUSIONS: These results suggest
      that NF1-associated pilocytic astrocytomas lack the genetic changes typically
      associated with the more clinically aggressive fibrillary astrocytomas and lay
      the foundation for future studies to identify NF1 JPA-specific alterations.

PMID- 11294926
TI  - TNFalpha promoter region gene polymorphisms in carbamazepine-hypersensitive
      patients.
AB  - OBJECTIVE: To evaluate whether the major histocompatibility complex contains
      susceptibility genes for carbamazepine hypersensitivity. Carbamazepine
      hypersensitivity is immune-mediated, although factors determining its occurrence
      and severity are unknown. METHODS: Using PCR in 60 carbamazepine-hypersensitive
      patients, 37 with nonserious (Group I) and 23 with serious (Group II) reactions,
      and 313 control subjects (63 patients on carbamazepine without adverse effects
      and 250 healthy volunteers), the association with polymorphisms in the promoter
      region of the tumor necrosis factor alpha (TNFalpha) gene (positions -308 and 
      238), and with HLA-DR3 and -DQ2 was determined. RESULTS: The frequency of the
      variant allele (TNF2) at the -308 position was increased in Group II but not
      Group I carbamazepine-hypersensitive patients compared with all control subjects
      (p = 0.01; OR = 2.4), as was the frequency of HLA-DR3 (p = 0.01; OR = 3.3), HLA
      DQ2 (p = 0.04; OR = 2.7), and the TNF2-DR3-DQ2 haplotypes (p = 0.02; OR = 3.2).
      None of the alleles were independently associated with serious carbamazepine
      hypersensitivity. For the -238 polymorphism, there was a difference in the
      genotype, but not in the allelic, frequencies between Group II hypersensitive
      patients and all control subjects. CONCLUSIONS: The TNF2 allele was associated
      with severe, but not nonserious, carbamazepine hypersensitivity reactions,
      suggesting that hypersecretion of tumor necrosis factor alpha may be a
      determinant of the severity of tissue damage. However, the association of the
      TNF2 allele with carbamazepine hypersensitivity was not independent of HLA-DR3
      and -DQ2, and therefore the possibility that it constitutes a passive component
      of the TNF2-DR3-DQ2 haplotype cannot be excluded.

PMID- 11294927
TI  - Neocortical abnormalities of [11C]-flumazenil PET in mesial temporal lobe
      epilepsy.
AB  - OBJECTIVE: To characterize abnormalities in neocortical central benzodiazepine
      receptor (cBZR) binding in patients with mesial temporal lobe epilepsy (mTLE)
      with unilateral hippocampal sclerosis (HS) using [(11)C]-flumazenil-(FMZ) PET and
      complementary voxel-based and quantitative volume-of-interest (VOI) methods.
      METHODS: The authors studied 13 control subjects and 15 patients with refractory
      mTLE and unilateral HS with [(11)C]-FMZ PET. Data were corrected for partial
      volume effect in the interactively outlined hippocampus and in 28 cortical VOI
      using an individualized template. A voxel-based analysis was also performed using
      statistical parametric mapping (SPM). RESULTS: Fourteen patients with mTLE had
      reduced [(11)C]-FMZ volume distribution (V(d)) in the hippocampus ipsilateral to
      the EEG focus, extending into the amygdala in four. Five patients showed
      additional significant neocortical abnormalities of [(11)C]-FMZ binding: temporal
      neocortical increases (1), extratemporal decreases (2), extratemporal increases
      only (1), and temporal and extratemporal neocortical increases (1). Group VOI
      analysis revealed significant reductions only in the ipsilateral hippocampus. SPM
      showed decreased [(11)C]-FMZ-V(d) in the ipsilateral hippocampus in 13 of 15
      patients, extending into the amygdala in eight. Five patients showed additional
      neocortical abnormalities: temporal neocortical increases only (3), extratemporal
      decreases (1), or both temporal neocortical and extratemporal decreases (1).
      Group analysis showed significant reductions in the ipsilateral hippocampus only.
      CONCLUSIONS: A combination of VOI- and voxel-based analysis of [(11)C]-FMZ PET
      detected extrahippocampal changes of cBZR binding in eight of 15 patients with
      mTLE due to HS. The finding of abnormalities in patients who were thought to have
      unilateral HS only based on MRI suggests that more widespread abnormalities are
      present in HS.

PMID- 11294928
TI  - Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical
      dysplasia.
AB  - OBJECTIVE: Focal cortical dysplasia is characterized by disorganized cortical
      lamination, dysplastic and heterotopic neurons, and an association with epilepsy.
      The contribution that dysplastic and heterotopic neurons make to epileptogenesis
      in focal cortical dysplasia is unknown and the phenotype of these cells may be
      distinct. The authors hypothesized that the expression of genes encoding
      glutamatergic (glutamate [GluR] and N-methyl-D-aspartate NMDA receptors [NR]) and
      gamma-aminobutyric acid A receptor (GABA(A)R) subunits is distinct in dysplastic
      and heterotopic neurons and that changes in receptor gene expression could be
      defined in a cell-specific pattern. METHODS: Single immunohistochemically labeled
      dysplastic and heterotopic neurons were microdissected from human focal cortical
      dysplasia specimens obtained during epilepsy surgery. Pyramidal neurons were
      microdissected from postmortem control cortex and from temporal cortex without
      dysplasia resected during temporal lobectomy. Poly (A) messenger RNA (mRNA) from
      single neurons was amplified, radiolabeled, and used to probe complementary DNA
      (cDNA) arrays containing GluR(1-6), NR(1A,1B), NR(2A-D), and GABA(A)Ralpha(1-6),
      and -Rbeta(1-3) subunit cDNAS: The relative hybridization intensities of each
      mRNA-cDNA hybrid were quantified by phosphorimaging. RESULTS: GluR, NR, and
      GABA(A)R subunit mRNA expression did not differ between control neurons and
      nondysplastic epilepsy specimens. Expression of GluR(4), NR(2B), and NR(2C)
      subunit mRNA was increased, and NR(2A) and GABA(A)Rbeta(1) subunit mRNA was
      decreased in dysplastic compared with pyramidal and heterotopic neurons. In
      contrast, GABA(A)Ralpha(1), -Ralpha(2), and -Rbeta(2) as well as GluR(1) mRNA
      levels were reduced in both dysplastic and heterotopic neurons. CONCLUSIONS:
      Differential expression of GluR, NR, and GABA(A)R mRNA in dysplastic and
      heterotopic neurons demonstrates cell specific gene transcription changes in
      focal cortical dysplasia. These results suggest that dysplastic and heterotopic
      neurons may be pharmacologically distinct and make differential contributions
      epileptogenesis in focal cortical dysplasia.

PMID- 11294929
TI  - Diffusion MRI in ischemic stroke compared to pathologically verified infarction.
AB  - BACKGROUND: Diffusion MRI abnormality correlates with pathology in animal
      ischemic stroke models. A combined retrospective and prospective analysis of
      consecutive patients over a 3-year period who had a clinical diagnosis of
      probable new ischemic stroke, underwent diffusion MRI, and were later studied at
      autopsy was performed. METHODS: Inclusion criteria for the retrospective analysis
      were 1) symptom onset within 14 days of presentation, 2) diffusion MRI within 28
      days of symptom onset, and 3) autopsy within 16 weeks of symptom onset. Patients
      with suspected further infarcts between MRI and autopsy were excluded. The
      locations of all areas of MRI abnormality were identified by a blinded
      neuroradiologist, and recent infarcts were identified by review of pathologic
      records and microscopic slides. RESULTS: Eleven patients were identified who
      fulfilled inclusion criteria, with 25 discrete pathologic infarcts. Diffusion MRI
      abnormality corresponded to pathologically verified infarction in 23 cases, was
      present in two locations where no pathologic infarct was identified, and was
      absent in two locations where an infarct was present at autopsy. In two cases,
      despite clinical suspicion of acute ischemic stroke, no MRI abnormality or
      pathologic infarct was found. The sensitivity and specificity of diffusion MRI
      were 88.5% (95% CI, 69.9% to 97.6%) and 96.6% (95% CI, 91.5% to 99.1%). Accuracy
      was 95.1% (95% CI, 90.2% to 98%). Three further patients who died during the
      course of the retrospective analysis were studied prospectively, and are
      described separately. CONCLUSIONS: These findings suggest high accuracy of
      diffusion MRI for detection of ischemic infarction compared with pathologic
      examination.

PMID- 11294930
TI  - Longitudinal study of blood pressure and white matter hyperintensities: the EVA
      MRI Cohort.
AB  - OBJECTIVE: To investigate the relationship between baseline hypertension and
      severity of white matter hyperintensities (WMH) at 4-year follow-up in a sample
      of subjects aged 59 to 71 years old at entry. METHODS: Subjects were participants
      in the Epidemiology of Vascular Ageing study, a longitudinal study on vascular
      aging and cognitive decline. At 4-year follow-up, 845 subjects had a cerebral
      MRI. MRI examinations were read by a single rater to determine the severity of
      WMH, ranging from absent to severe. Hypertension at each wave of the study was
      defined as systolic blood pressure > or =160 mm Hg, diastolic blood pressure > or
      =95 mm Hg, or use of antihypertensive medication. RESULTS: Hypertension at
      baseline was significantly associated with an increased risk of having severe WMH
      at 4-year follow-up. When taking into account both blood pressure levels and
      antihypertensive drug intake, analysis showed that the risk of having severe WMH
      was significantly reduced in subjects with normal blood pressure taking
      antihypertensive medication compared with those with high blood pressure taking
      antihypertensive agents. Cross-sectional relationships between hypertension and
      WMH at 4-year follow-up showed that the frequency of severe WMH was significantly
      higher in people who were hypertensive at both baseline and 4-year follow-up than
      those who were hypertensive only at 4-year follow-up. CONCLUSIONS: Hypertension
      is a major risk factor for severe WMH. Subjects taking antihypertensive drugs and
      who have controlled blood pressure had a reduced risk of severe WMH. Longitudinal
      studies are needed to investigate whether reduction of the development of WMH, by
      treatment and prevention of hypertension, might reduce the subsequent risk of
      cognitive deterioration or stroke.

PMID- 11294931
TI  - Investigation of MS normal-appearing brain using diffusion tensor MRI with
      clinical correlations.
AB  - OBJECTIVE: To quantitatively investigate water diffusion changes in normal
      appearing white matter (NAWM) and gray matter in patients with MS, and to
      evaluate whether these changes are correlated with clinical disability and
      disease duration. BACKGROUND: Diffusion tensor imaging provides quantitative
      information about the magnitude and directionality (anisotropy) of water
      diffusion in vivo and detects pathologic changes in MS brain tissue. METHODS:
      Diffusion tensor imaging was performed in 39 patients with MS and in 21 age
      matched control subjects. Quantitative indices, including fractional anisotropy,
      volume ratio, and mean diffusivity, were obtained in 30 regions of interest
      located in normal-appearing basal ganglia, cerebellar gray matter, and
      supratentorial and infratentorial NAWM. RESULTS: Patients with MS showed
      significantly reduced anisotropy and a trend toward increased diffusivity in the
      infratentorial and supratentorial NAWM, and significantly increased anisotropy in
      the basal ganglia. In all patients with MS, both fractional anisotropy and mean
      diffusivity in the cerebral peduncles were inversely correlated with the Expanded
      Disability Status Scale and pyramidal functional scores. In patients with
      relapsing-remitting MS, there was a strong correlation between Expanded
      Disability Status Scale score and fractional anisotropy in both supratentorial
      and infratentorial NAWM. In primary and secondary progressive MS, disease
      duration correlated strongly with mean diffusivity in infratentorial NAWM and
      fractional anisotropy in the cerebral peduncles, respectively. CONCLUSION: The
      most striking finding of decreased fractional anisotropy in supratentorial and
      infratentorial NAWM and increased fractional anisotropy in basal ganglia may
      result from axonal degeneration due to fiber transection in remote focal lesions.
      Diffusion tensor imaging indices, in particular fractional anisotropy, appear
      sensitive to structural damage in NAWM that is associated with disability and
      progression in MS.

PMID- 11294932
TI  - Comparisons of patient self-report, neurologic examination, and functional
      impairment in MS.
AB  - OBJECTIVE: To compare the recently developed Guy's Neurologic Disability Scale
      (GNDS), based on patient self-report, with both neurologist rating of neurologic
      examination abnormalities using the Expanded Disability Status Scale (EDSS) and
      observations of functional impairment on the Multiple Sclerosis Functional
      Composite (MSFC) in the assessment of disease impact in MS. METHODS: Two hundred
      ninety MS patients were recruited at an outpatient clinic. Impairment and
      disability were assessed using GNDS, EDSS, and MSFC. Correlations between GNDS,
      EDSS, MSFC, and their corresponding components were studied for the total
      population, MS phenotypes, and three disability strata. RESULTS: Mean scores were
      4.6 (SD, 2.0) for EDSS, 0.0 (SD, 0.8) for MSFC, and 14.6 (SD, 7.9) for GNDS. Good
      correlations were found between GNDS and EDSS (r = 0.73), between GNDS and MSFC
      (r = -0.68), and between different subcategories of the GNDS and EDSS, MSFC, and
      their corresponding components. Remarkably good correlations were found between
      lower limb function and all three scales. Poor correlations were also found,
      especially between different measurements focusing on cognitive function.
      CONCLUSION: The good correlations between GNDS and both EDSS and MSFC were mainly
      due to the importance of spinal-cord-related neurologic functions in all three
      scoring systems. A marked discrepancy was found for the assessment of cognition
      between objective measurements and subjective complaints. Because patients' self
      reporting correlates well with results of physical examination, GNDS can offer a
      valuable way to measure disease impact in MS. However, GNDS is not an adequate
      screen of cognitive dysfunction.

PMID- 11294933
TI  - Influenza vaccination in MS: absence of T-cell response against white matter
      proteins.
AB  - BACKGROUND: Natural infections bear the risk of triggering MS bouts, whereas
      epidemiologic studies have not delineated an increased risk for disease activity
      after influenza virus vaccination. OBJECTIVE: To examine influenza A virus
      specific and myelin protein-reactive T-cell frequencies by interferon gamma
      (IFNgamma)-enzyme-linked immunospot and the response of these cells by IFNgamma
      reverse transcription (RT) PCR after immunization and any incidental upper
      respiratory tract infection (URI) in 12 patients with MS (seven with a relapsing
      remitting course; five with a secondary progressive course; Kurtzke Expanded
      Disability Status Scale [EDSS] score from 1.0 to 6.5, without immunosuppressive
      treatment) and 28 healthy volunteers. RESULTS: A cellular immune response against
      influenza A virus was mounted in both populations at 2 weeks after vaccination.
      Patients with MS showed a higher relative increase (p = 0.008) than controls with
      respect to the number of influenza-specific T cells. Mean antibody responses
      against influenza A virus were increased in both populations after 2 weeks (p <
      0.01). Despite these virus-specific reactions, no increase in T-cell frequencies
      responsive to human myelin basic protein (MBP) or recombinant human myelin
      oligodendrocyte protein (MOG) was observed after immunization, arguing against a
      general immune stimulation by influenza vaccination. In contrast, MBP-specific T
      cell responses became detectable in several individuals after febrile infection.
      CONCLUSION: These data support the clinical observations that influenza
      vaccination is effective and safe in patients with MS with respect to cellular
      immunoreactivity against two main CNS myelin proteins.

PMID- 11294934
TI  - Cortical degeneration associated with phonologic and semantic language
      impairments in AD.
AB  - OBJECTIVE: To compare the pattern of cortical degeneration associated with
      different language deficits in cases of AD. METHODS: Cases for detailed
      neuropathologic analysis (Patients 1 and 2) were selected because of their
      detailed clinical and neuropsychological assessments of language dysfunction in
      AD. Patient 1 had severe phonologic impairment with relatively preserved semantic
      aspects of language. Patient 2 had severe semantic language impairment with
      relatively preserved phonologic skills. The tissue volume of cortical regions
      associated with speech and language function was measured using standardized
      three-dimensional techniques. Neuronal areal fraction was also measured from
      histologic tissue samples. The degree of volume atrophy and neuronal loss was
      calculated in comparison to control measures (n = 10 men and 11 women).
      Measurements more than 2 SD from controls were considered abnormal. RESULTS: Both
      AD cases had significant degeneration of the superior temporal gyrus and area 37.
      Cortical language regions affected only in Patient 1 included the anterior and
      posterior insula and part of Broca's area. In contrast, Patient 2 had a greater
      degree of degeneration in the temporal gyri and their white matter connections
      with the hippocampal/entorhinal complex. CONCLUSIONS: Variable patterns of
      neurodegeneration underlie the clinical differences observed in patients with AD.
      Disconnection within the temporal lobe appears associated with semantic language
      difficulties, whereas disconnection of the anterior and posterior language areas
      appears associated with phonologic and grammatical impairment.

PMID- 11294935
TI  - SPECT perfusion imaging in the diagnosis of Alzheimer's disease: a clinical
      pathologic study.
AB  - OBJECTIVE: Numerous studies have suggested that temporoparietal hypoperfusion
      seen on brain imaging with SPECT may be useful in diagnosing AD during life.
      However, these studies have often been limited by lack of pathologic validation
      and unrepresentative samples. The authors performed this study to determine
      whether SPECT imaging provides diagnostically useful information in addition to
      that obtained from a clinical examination. METHODS: Clinical data and SPECT
      images were collected prospectively, and patients were followed to autopsy.
      Clinical history, pathologic findings, and SPECT images were each evaluated by
      raters blind to other features, and clinical and SPECT diagnoses were compared
      with pathologic diagnoses. The study population consisted of 70 patients with
      dementia, followed to autopsy; 14 controls followed to autopsy; and 71 controls
      (no autopsy performed). The primary outcome was the likelihood of a pathologic
      diagnosis of AD given a positive clinical diagnosis, a positive SPECT diagnosis,
      and both. RESULTS: When all participants (patients and controls) were included in
      the analysis, the clinical diagnosis of "probable" AD was associated with an 84%
      likelihood of pathologic AD. A positive SPECT scan raised the likelihood of AD to
      92%, whereas a negative SPECT scan lowered the likelihood to 70%. SPECT was more
      useful when the clinical diagnosis was "possible" AD, with the likelihood of 67%
      without SPECT, 84% with a positive SPECT, and 52% with a negative SPECT. Similar
      results were found when only patients with dementia were included in the
      analysis. CONCLUSIONS: In the evaluation of dementia, SPECT imaging can provide
      clinically useful information indicating the presence of AD in addition to the
      information that is obtained from clinical evaluation.

PMID- 11294936
TI  - Comparison of apraxia in corticobasal degeneration and progressive supranuclear
      palsy.
AB  - OBJECTIVE: To describe ideomotor apraxia in patients with corticobasal
      degeneration and those with progressive supranuclear palsy, two parkinsonian
      disorders that are often misdiagnosed due to the overlap in their clinical
      features, and to determine whether systematic apraxia testing is useful for
      differential diagnosis. METHODS: Fourteen patients fulfilling National Institute
      of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy
      clinical criteria for progressive supranuclear palsy, 13 patients fulfilling
      modified Lang criteria for corticobasal degeneration, and 12 normal healthy
      control subjects were given the Test of Oral and Limb Apraxia, which was scored
      according to the Florida Apraxia Battery for occurrence of various types of
      apraxic errors. RESULTS: Both patients with progressive supranuclear palsy and
      corticobasal degeneration committed a greater number of apraxic errors than
      normal healthy control subjects on both transitive and intransitive tasks (p <
      0.001 in both cases), but apraxia was much more severe in patients with
      corticobasal degeneration than progressive supranuclear palsy (p < 0.001). The
      index of apraxia severity, in combination with the assessment of the two key
      features of progressive supranuclear palsy (falls and vertical gaze palsy),
      correctly classified all patients. CONCLUSIONS: Patients with corticobasal
      degeneration show more severe ideomotor apraxia than patients with progressive
      supranuclear palsy, and systematic assessment of ideomotor apraxia facilitates
      the differential diagnosis between patients with progressive supranuclear palsy
      and those with corticobasal degeneration.

PMID- 11294937
TI  - Cocaine-induced persistent dyskinesias.
AB  - The authors report a 34-year-old woman with a history of extensive cocaine abuse
      who developed choreodystonic dyskinesias and an obsessive-compulsive behavior
      disorder. The abnormal movements and behavior disorder persisted after a 20-month
      cocaine-free period.

PMID- 11294938
TI  - Memory impairment in abstinent MDMA ("Ecstasy") users: a longitudinal
      investigation.
AB  - To examine the neurotoxic potential of continued MDMA ("Ecstasy") use in humans
      and its functional consequences over the course of 1 year, 15 MDMA users
      participated in a longitudinal study in which they completed a brief
      neuropsychological test battery composed mainly of retrospective and prospective
      memory tasks. Subjects were abstinent for 2 weeks on initial and 1-year testing.
      Continued use of MDMA was associated with progressive decline in terms of
      immediate and delayed recall.

PMID- 11294939
TI  - Head size and cognitive ability in nondemented older adults are related.
AB  - In a cross-sectional analysis of 818 healthy older individuals (aged 50 to 81
      years), head size was found to be related to performance on tests measuring
      intelligence, global cognitive functioning, and speed of information processing,
      but not memory. These relations were not confounded by educational level,
      socioeconomic background, or height. Large head/brain size may protect elderly
      people against cognitive deterioration, supporting a reserve hypothesis of brain
      aging.

PMID- 11294940
TI  - Amygdala and hippocampal volumes in children with Down syndrome: a high
      resolution MRI study.
AB  - The objective of this study was to use high-resolution MRI techniques to
      determine whether children with Down syndrome exhibit decreases in hippocampal
      and amygdala volumes similar to those demonstrated in recent studies of adults
      with this condition. When corrected for overall brain volumes, amygdala volumes
      did not differ between groups but hippocampal volumes were significantly smaller
      in the Down syndrome group. These findings suggest that the hippocampal volume
      reduction seen in adults with Down syndrome may be primarily due to early
      developmental differences rather than neurodegenerative changes.

PMID- 11294941
TI  - Stroke as a complication of cardiac catheterization: risk factors and clinical
      features.
AB  - The authors aimed to delineate the risk factors and radiologic pattern of stroke
      complicating cardiac catheterization. Twenty-two cases were matched with three
      control subjects. Stroke was significantly associated with severity of coronary
      artery disease and length of fluoroscopy time (OR 1.96 and 1.65). The use of MRI
      with diffusion weighting allowed the identification of multiple asymptomatic
      lesions and a subset of lacunar-type infarcts (23%), which most likely occurred
      on an atheroembolic basis.

PMID- 11294942
TI  - Spontaneous spinal cord herniation.

PMID- 11294943
TI  - Tinnitus evoked by finger movement: brain plasticity after peripheral
      deafferentation.

PMID- 11294944
TI  - CSF tau and Abeta42 levels in patients with Down's syndrome.

PMID- 11294945
TI  - Accumulation of alpha-synuclein in autonomic nerves in pure autonomic failure.

PMID- 11294946
TI  - Pathology of PD in monozygotic twins with a 20-year discordance interval.

PMID- 11294947
TI  - A polymorphism in the intronic region of the IL-1alpha gene and the risk for
      Parkinson's disease.

PMID- 11294948
TI  - Smoking, alcohol, and coffee consumption preceding Parkinson's disease.

PMID- 11294949
TI  - Sleep disordered breathing in patients with cluster headache.

PMID- 11294950
TI  - Left vagus nerve stimulation suppresses experimentally induced pain.

PMID- 11294951
TI  - Misleading results with the 14-3-3 assay for the diagnosis of Creutzfeldt-Jakob
      disease.

PMID- 11294952
TI  - Iatrogenic Creutzfeldt-Jakob disease at the millennium.

PMID- 11294953
TI  - Headache-related disability in the management of migraine.

PMID- 11294954
TI  - The impact of migraine: Epidemiology, risk factors, and co-morbidities.
AB  - In Western countries, recent community-based studies of migraine prevalence using
      standardized diagnostic criteria give 1-year prevalence estimates of around 10 to
      12%. The prevalence of migraine is age- and gender-dependent. Age at onset of
      migraine is earlier in boys than in girls. Migraine is two to three times more
      common in women than in men, with peak prevalence occurring during mid-life in
      both sexes. Current evidence also indicates that migraine prevalence is higher in
      Caucasians than in Africans or Asians. In some migraineurs, attacks may be
      frequent or prolonged, leading to considerable pain and disability. There has
      been much debate over predisposing factors, which are not sufficient by
      themselves to cause an attack, as well as precipitants, which immediately precede
      the attack. However, convincing data are lacking for most of these. Significant
      associations have been reported between migraine and certain psychiatric
      disorders, epilepsy, and stroke in women under the age of 45. These findings
      demonstrate that migraine is common, has a substantial impact on sufferers, and
      may be associated with other disorders.

PMID- 11294955
TI  - Migraine-related disability: impact and implications for sufferers' lives and
      clinical issues.
AB  - Migraine is a common, debilitating disorder that imposes a large personal burden
      on sufferers and high economic costs on society. Sufferers have a significant
      level of migraine-related disability in all aspects of their daily lives,
      including employment, household work, and non-work activities. Despite this
      burden of illness, physicians often do not diagnose or treat the illness
      effectively. Physicians consider that specific treatment is necessary when
      disability information is known but, until recently, no criteria have been
      available for assessment of migraine severity. Two studies indicate that
      information on disability is an important criterion in assessing migraine
      severity and influences physicians in their judgments of illness severity and
      treatment needs. However, physicians and patients often do not seek or share
      migraine-associated disability, which may contribute to suboptimal management.
      Efforts to improve knowledge of headache-related disability in the consultation
      have the potential to improve migraine management. An assessment tool that could
      reliably quantify headache-related disability has the potential for grading
      migraine severity and improving care.

PMID- 11294956
TI  - Development and testing of the Migraine Disability Assessment (MIDAS)
      Questionnaire to assess headache-related disability.
AB  - The MIDAS Questionnaire was developed to assess headache-related disability with
      the aim of improving migraine care. Headache sufferers answer five questions,
      scoring the number of days, in the past 3 months, of activity limitations due to
      migraine. The internal consistency, test-retest reliability, and validity
      (accuracy) of the questionnaire were assessed in separate population-based
      studies of migraine sufferers. In addition, the face validity, ease of use, and
      clinical utility of the questionnaire were evaluated in a group of 49 physicians
      who independently rated disease severity and need for care in a diverse sample of
      migraine case histories. The test-retest Pearson correlation coefficient for the
      total MIDAS score was approximately 0.8. The MIDAS score was valid when compared
      with a reference diary-based measure of disability; the overall correlation
      between MIDAS and the diary-based measure was 0.63. The MIDAS score was also
      correlated with physicians' assessments of need for medical care (r = 0.69). From
      studies completed to date, the MIDAS Questionnaire has been shown to be
      internally consistent, highly reliable, valid, and correlates with physicians'
      clinical judgment. These features support its suitability for use in clinical
      practice. Use of the MIDAS Questionnaire may improve physician-patient
      communication about headache-related disability and may favorably influence
      health-care delivery for migraine patients.

PMID- 11294957
TI  - Potential of the Migraine Disability Assessment (MIDAS) Questionnaire as a public
      health initiative and in clinical practice.
AB  - Migraine is not always well managed in clinical practice, often being under
      diagnosed and under-treated. As a result, many sufferers never consult a
      physician or lapse from care after physician contact. Although most migraine care
      is provided by general practitioners, others, including specialists, emergency
      room physicians, pharmacists, and alternative practitioners, may also be
      involved. A method of standardizing clinical information about migraine is
      essential for coordinated, logical, and systematic care. The impact of migraine
      on the patient is an important clinical parameter but one that is seldom inquired
      about, perhaps because it exhibits such marked variability among and within
      individuals. Headache-related disability can be an objective and measurable index
      of this impact. The Migraine Disability Assessment (MIDAS) Questionnaire is a
      simple and validated instrument with potential for use in clinical practice,
      research, and public health. It can improve communication between patients and
      health-care professionals regarding the impact of migraine which, in turn, allows
      tailoring of the intensity of treatment to the severity of the illness. Changes
      in the MIDAS score may serve as an end point in assessing treatment efficacy. In
      populations, MIDAS scores may indicate the burden of migraine in the community
      and spark public health initiatives to improve management.

PMID- 11294958
TI  - The role of headache-related disability in migraine management: implications for
      headache treatment guidelines.
AB  - Recently published US Headache Consortium Guidelines recommend a process of
      diagnosis, patient education, and individualized treatment for the management of
      migraine. Clinicians are advised to base their treatment choice on attack
      frequency and duration, degree of disability, non-headache symptoms, patient
      preference, and prior history of treatment response, using a stratified approach
      to care. In stratified care, initial treatment is individualized based on an
      assessment of the patients' medical needs. One approach to stratification uses
      the Migraine Disability Assessment (MIDAS) Questionnaire to stratify patients
      into groups with different treatment needs based on the degree of headache
      related disability. Stratified care was developed as an alternative to step-care
      approaches, which begin patients on nonspecific medication with gradual
      escalation until they obtain effective relief. Results from the Disability in
      Strategies for Care (DISC) study indicate that stratified care provides superior
      outcomes compared to step-care and that the approach is cost-effective,
      supporting the US Headache Consortium GUIDELINES: Stratified care may become the
      approach of choice for managing migraine in clinical practice. This approach
      increases the chances of providing appropriate therapy at the patient's initial
      consultation, sparing the patient a series of failed therapeutic efforts. The
      MIDAS Questionnaire provides a practical tool for helping to implement the
      recommendations of the US Headache Consortium

PMID- 11294959
TI  - Rapid cardiology--for chest pain, breathlessness and palpitations.

PMID- 11294960
TI  - Current trends in the management of thromboembolic events.

PMID- 11294961
TI  - Why is there so much end-stage renal failure of undetermined cause in UK Indo
      Asians?
AB  - There is a high incidence of end-stage renal failure (ESRF) of undetermined cause
      in the Indo-Asian population of the UK. We studied patients presenting from the
      district of Brent and Harrow, which has a large Indo-Asian community, and whose
      renal services are largely provided by our centre. The diagnosis and ethnicity of
      patients starting renal replacement therapy and/or undergoing renal biopsy were
      collated. The incidences of ESRF, rates of renal biopsy and underlying diagnoses
      were calculated for Indo-Asians and Caucasians. Requirement for renal replacement
      therapy in Indo-Asians presenting to our centre from Brent and Harrow was
      221/10(6)/year; no underlying diagnosis was identified in 77/10(6)/year. Renal
      biopsy rate in these patients was 456/10(6)/year, and the diagnostic categories
      significantly over-represented compared to Caucasians were: hypertension and
      ischaemia, focal segmental glomerulosclerosis (FSGS), idiopathic interstitial
      nephritis (IIN), diabetic nephropathy, minor glomerular abnormality, lupus
      nephritis and non-specific advanced chronic renal disease (p<0.001). The first
      three of these had a combined incidence of 135/10(6)/year in Indo-Asians and
      31/10(6)/year in Caucasians. ESRF of undetermined cause is common in UK Indo
      Asians, as is requirement for renal biopsy. Hypertension with ischaemia, FSGS and
      IIN are over-represented in the Indo-Asian population, and should be targeted for
      early diagnosis and treatment in this group.

PMID- 11294962
TI  - Serum IgA tissue transglutaminase antibodies in coeliac disease and other
      gastrointestinal diseases.
AB  - We investigated the presence of IgA anti-tissue transglutaminase (tTG) antibodies
      in untreated coeliac disease (CD) and other gastrointestinal diseases, and
      compared IgA tTG concentrations with anti-endomysium (EMA) immunofluorescent
      findings. The study included 116 untreated CD patients (74 female, 42 male, age
      range 15-78 years, median 47 years), 82 treated CD patients, 65 patients with
      normal duodenal histology, 260 disease control samples and 29 healthy volunteers.
      IgA anti-tTG, EMA, and anti-gliadin (AGA) antibodies were measured. Serum total
      IgA was measured in the CD patients. Two IgA-deficient untreated CD patients were
      excluded. IgA EMA and IgA AGA were positive in 99 (87%) and 69 (61%),
      respectively, of the 114 untreated CD patients. Elevated IgA anti-tTG were found
      in 92/114 (81%) untreated coeliacs, 1/82 (1%) treated coeliacs, 2/65 (3%) non
      coeliacs, 10/260 (4%) disease controls and 2/29 (7%) volunteers. Four of the
      untreated CD patients, with a normal serum total IgA concentration, were negative
      for all the serological tests. IgA anti-tTG concentrations were significantly
      higher in untreated coeliacs (median 10200 units/ml) than in other groups (Mann
      Whitney, p<0.00001) and compared well with IgA EMA titres (r(2)=0.54; p<0.0001).

PMID- 11294963
TI  - The diagnosis of leprosy is delayed in the United Kingdom.
AB  - Diagnostic delay in leprosy can have serious neurological consequences for the
      patient. We studied the presentation of leprosy patients, focusing on delays in
      diagnosis, in a retrospective case-note review of 28 patients referred to The
      Hospital for Tropical Diseases during 1995-1998. The median ages at onset of
      symptoms and at diagnosis were 25.1 years (range 9-77.7) and 30.1 years (range 9
      78.3), respectively. The median time from symptom onset to diagnosis was 1.8
      years (0.2-15.2). Prior to referral to a leprologist, patients had seen a
      dermatologist (20), neurologist (9), orthopaedic surgeon (5) and rheumatologist
      (2). Delay in diagnosis occurred in 82% of cases. Misdiagnoses as dermatological
      and neurological conditions were important causes of delay, and 68% of patients
      had nerve damage resulting in disability. Leprosy can be difficult to diagnose
      outside endemic areas. Increased awareness amongst general practitioners and
      hospital specialists would lead to more rapid diagnosis, thus minimizing damage
      and disability.

PMID- 11294964
TI  - The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred.
AB  - The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant
      disease characterized by the occurrence of parathyroid tumours and fibro-osseous
      tumours of the jaw bones. Some HPT-JT patients may also develop renal
      abnormalities, which include Wilms' tumours, hamartomas and polycystic disease.
      The HPT-JT gene has been mapped to chromosome 1q25-q31, and we report the
      clinical and genetic findings in a kindred from central Portugal. HPT-JT was
      observed in six members from three generations; all had primary
      hyperparathyroidism (five had parathyroid adenomas, one a parathyroid carcinoma).
      Ossifying jaw fibromas affecting the maxilla and/or mandible were observed in
      5/6. Renal cysts (<2.5 cm) were observed in four. Genetic studies using 18
      polymorphic loci from chromosome 1q25-q31, together with leukocyte DNA from 11
      family members and tumour DNA from three parathyroids (two adenomas and one
      carcinoma), revealed loss of tumour heterozygosity in the parathyroid carcinoma
      only, and the retained haplotype was found to cosegregate with the disease in the
      six affected members. A new Portuguese kindred with the HPT-JT syndrome that maps
      to chromosome 1q25-q31 has been identified, and these findings will help in the
      further characterization of this inherited disorder.

PMID- 11294965
TI  - Clostridium difficile infection, hospital geography and time-space clustering.
AB  - To analyse spatial and temporal relationships of Clostridium difficile-associated
      disease in an inner-city hospital, we retrospectively evaluated 283 episodes of
      confirmed C. difficile diarrhoea in the Chelsea and Westminster Hospital between
      1995 and 1998, against a background of relatively stable case mix, antibiotic
      usage and admission numbers, using Knox analysis to determine the presence of
      disease clustering in time and space. We found five time-space clusters on four
      medical wards and between two adjacent units. The clusters were not related to
      the overall case number on single wards, and were separated in time. Knox time
      space analysis provides a simple screening tool to identify disease clusters,
      assess the efficacy of infection control measures and the influence of hospital
      geography and traffic. The results support the importance of infection control
      measures in the prevention of C. difficile-related disease.

PMID- 11294966
TI  - Bioterrorism.

PMID- 11294967
TI  - Renal tubule tumor induction by tertiary-butyl alcohol.

PMID- 11294968
TI  - Herbert E. Stokinger, "Mr. TLV".

PMID- 11294969
TI  - Implications of apoptosis for toxicity, carcinogenicity, and risk assessment:
      fumonisin B(1) as an example.
AB  - The rates of cell proliferation and cell loss in conjunction with the
      differentiation status of a tissue are among the many factors contributing to
      carcinogenesis. Nongenotoxic (non-DNA reactive) chemicals may affect this balance
      by increasing proliferation through direct mitogenesis or through a regenerative
      response following loss of cells through cytotoxic (oncotic) or apoptotic
      necrosis. In a recent NTP study in Fischer rats and B6C3F(1) mice, the mycotoxin
      fumonisin B(1) caused renal carcinomas in male rats and liver cancer in female
      mice. In an earlier study in male BD-IX rats, fumonisin B(1) caused hepatic
      toxicity and hepatocellular carcinomas. An early effect of fumonisin B(1)
      exposure in these target organs is apoptosis. However, there is also some
      evidence of oncotic necrosis following fumonisin B(1) administration, especially
      in the liver. Induction of apoptosis may be a consequence of ceramide synthase
      inhibition and disruption of sphingolipid metabolism by fumonisin B(1). Fumonisin
      B(1) is not genotoxic in bacterial mutagenesis screens or in the rat liver
      unscheduled DNA-synthesis assay. Fumonisin B(1) may be the first example of an
      apparently nongenotoxic (non-DNA reactive) agent producing tumors through a mode
      of action involving apoptotic necrosis, atrophy, and consequent regeneration.

PMID- 11294970
TI  - Harmonization of cancer and noncancer risk assessment: proceedings of a consensus
      building workshop.
AB  - Significant advancements have been made toward the use of all relevant scientific
      information in health risk assessments. This principle has been set forth in risk
      assessment guidance documents of international agencies including those of the
      World Health Organization's International Programme on Chemical Safety, the U.S.
      Environmental Protection Agency, and Health Canada. Improving the scientific
      basis of risk assessment is a leading strategic goal of the Society of
      Toxicology. In recent years, there has been a plethora of mechanistic research on
      modes of chemical toxicity that establishes mechanistic links between noncancer
      responses to toxic agents and subsequent overt manifestations of toxicity such as
      cancer. The research suggests that differences in approaches to assessing risk of
      cancer and noncancer toxicity need to be resolved and a common broad paradigm for
      dose-response assessments developed for all toxicity endpoints. In November 1999,
      a workshop entitled "Harmonization of Cancer and Noncancer Risk Assessment" was
      held to discuss the most critical issues involved in developing a more consistent
      and unified approach to risk assessment for all endpoints. Invited participants
      from government, industry, and academia discussed focus questions in the areas of
      mode of action as the basis for harmonization, common levels of adverse effect
      across toxicities for use in dose-response assessments, and scaling and
      uncertainty factors. This report summarizes the results of those discussions.
      There was broad agreement, albeit not unanimous, that current science supports
      the development of a harmonized set of principles that guide risk assessments for
      all toxic endpoints. There was an acceptance among the participants that
      understanding the mode of action of a chemical is ultimately critical for
      nondefault risk assessments, that common modes of action for different toxicities
      can be defined, and that our approach to assessing toxicity should be
      biologically consistent.

PMID- 11294971
TI  - Applications of mechanistic data in risk assessment: the past, present, and
      future.
AB  - Mechanistic data, when available, have long been considered in risk assessment,
      such as in the development of the nitrate RfD based on effects in a sensitive
      group (infants). Recent advances in biology and risk assessment methods have led
      to a tremendous increase in the use of mechanistic data in risk assessment.
      Toxicokinetic data can improve extrapolation from animals to humans and
      characterization of human variability. This is done by the development of
      improved tissue dosimetry, by the use of uncertainty factors based on chemical
      specific data, and in the development of physiologically based pharmacokinetic
      (PBPK) models. The development of the boron RfD illustrates the use of chemical
      specific data in the improved choice of uncertainty factors. The draft cancer
      guidelines of the U.S. Environmental Protection Agency emphasize the use of mode
      of action data. The first choice under the guidelines is to use a chemical
      specific, biologically based dose-response (BBDR) model. In the absence of a BBDR
      model, mode of action data are used to determine whether low-dose extrapolation
      is done using a linear or nonlinear (margin of exposure) approach. Considerations
      involved in evaluating a hypothesized mode of action are illustrated using 1,3
      dichloropropene, and use of a BBDR model is illustrated using formaldehyde.
      Recent developments in molecular biology, including transgenic animals,
      microarrays, and the characterization of genetic polymorphisms, have significant
      potential for improving risk assessments, although further methods development is
      needed. Overall, use of mechanistic data has significant potential for reducing
      the uncertainty in assessments, while at the same time highlighting the areas of
      uncertainty.

PMID- 11294972
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce
      cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells.
AB  - Diindolylmethane (DIM) is an acid-catalyzed condensation product of indole-3
      carbinol, a constituent of cruciferous vegetables, and is formed in the stomach.
      DIM alters estrogen metabolism and inhibits carcinogen-induced mammary tumor
      growth in rodents. DIM is a weak agonist for the aryl hydrocarbon (Ah) receptor
      and blocks the effects of estrogens via inhibitory Ah receptor-estrogen receptor
      cross-talk. DIM and various structural analogs were examined in H295R cells for
      effects on 3 cytochrome P450 (CYP) enzymes involved in estrogen synthesis and/or
      metabolism: CYP1A1, CYP1B1, and CYP19 (aromatase). Aromatase activity was
      measured by conversion of 1 beta-(3)H-androstenedione to estrone and (3)H(2)O.
      H295R cells were exposed to the test chemicals dissolved in dimethyl sulfoxide
      for 24 h prior to analyses. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (0--30 nM)
      and DIM (0--10 microM) induced ethoxyresorufin-O-deethylase (EROD) activity, as a
      measure of CYP1A1 and possibly 1B1 activity, with EC(50) values of about 0.3 nM
      and 3 microM, respectively. DIM, but not TCDD, induced aromatase activity with an
      apparently maximal 2-fold increase at 10 microM; higher concentrations of DIM and
      many of its analogs were cytotoxic. TCDD (30 nM) significantly increased CYP1A1
      and 1B1 mRNA levels, but had no effect on mRNA for CYP19. DIM (3 microM)
      significantly increased mRNA levels for all three CYPS: DIM analogs with
      substitutions on the 5 and 5' position (3 microM) induced aromatase and EROD
      activity, together with mRNA levels of CYP1A1, 1B1, and 19; analogs that were
      substituted on the central carbon of the methane group showed little or no
      inductive activity toward the CYPS: In conclusion, DIM and several of its analogs
      appear to induce CYPs via multiple yet distinct pathways in H295R human
      adrenocortical carcinoma cells.

PMID- 11294973
TI  - Characterization of rat and human UDP-glucuronosyltransferases responsible for
      the in vitro glucuronidation of diclofenac.
AB  - In the current study, the identification of the rat and human UDP
      glucuronosyltransferase (UGT) isoforms responsible for the glucuronidation of
      diclofenac was determined. Recombinant human UGT1A9 catalyzed the glucuronidation
      of diclofenac at a moderate rate of 166-pmol/min/mg protein, while UGT1A6 and
      2B15 catalyzed the glucuronidation of diclofenac at low rates (<20-pmol/min/mg
      protein). Conversely, human UGT2B7 displayed a high rate of diclofenac
      glucuronide formation (>500 pmol/min/mg protein). Recombinant rat UGT2B1
      catalyzed the glucuronidation of diclofenac at a rate of 250-pmol/min/mg protein.
      Rat UGT2B1 and human UGT2B7 displayed a similar, low apparent Km value of <15
      microM for both UGT isoforms and high Vmax values 0.3 and 2.8 nmol/min/mg,
      respectively. Using diclofenac as a substrate, enzyme kinetics in rat and human
      liver microsomes showed that the enzyme(s) involved in diclofenac glucuronidation
      had a low apparent Km value of <20 microM and a high Vmax value of 0.9 and 4.3
      nmol/min/mg protein, respectively. Morphine is a known substrate for rat UGT2B1
      and human UGT2B7 and both total morphine glucuronidation (3-O- and 6-O
      glucuronides) and diclofenac glucuronidation reactions showed a strong
      correlation with one another in human liver microsome samples. In addition,
      diclofenac inhibited the glucuronidation of morphine in human liver microsomes.
      These data suggested that rat UGT2B1 and human UGT2B7 were the major UGT isoforms
      involved in the glucuronidation of diclofenac.

PMID- 11294974
TI  - Comparative xenobiotic metabolism between Tg.AC and p53+/- genetically altered
      mice and their respective wild types.
AB  - The use of transgenic animals, such as v-Ha-ras activated (TG:AC) and p53+/-
      mice, offers great promise for a rapid and more sensitive assay for chemical
      carcinogenicity. Some carcinogens are metabolically activated; therefore, it is
      critical that the altered genome of either of these model systems does not
      compromise their capability and capacity for metabolism of xenobiotics. The
      present work tests the generally held assumption that xenobiotic metabolism in
      the TG:AC and p53+/- mouse is not inherently different from that of the
      respective wild type, the FVB/N and C57BL/6 mouse, by comparing each genotype's
      ability to metabolize benzene, ethoxyquin, or methacrylonitrile. Use of these
      representative substrates offers the opportunity to examine arene oxide
      formation, aromatic ring opening, hydroxylation, epoxidation, O-deethylation, and
      a number of conjugation reactions. Mice were treated by gavage with (14)C-labeled
      parent compound, excreta were collected, and elimination routes and rates, as
      well as (14)C-derived metabolite profiles in urine, were compared between
      relevant treatment groups. Results of this study indicated that metabolism of the
      3 parent compounds was not appreciably altered between either FVB/N and TG:AC
      mice or C57BL/6 and p53+/- mice. Further, expression of CYP1A2, CYP2E1, CYP3A,
      and GST-alpha in liver of naive genetically altered mice was similar to that of
      corresponding wild-type mice. Thus, these results suggest that the inherent
      ability of TG:AC and p53+/- mice to metabolize xenobiotics is not compromised by
      their altered genomes and would not be a factor in data interpretation of
      toxicity studies using either transgenic mouse line.

PMID- 11294975
TI  - Toxicokinetics of methyl tert-butyl ether and its metabolites in humans after
      oral exposure.
AB  - Methyl tert-butyl ether (MTBE) is widely used as an additive to gasoline, to
      increase oxygen content and reduce tailpipe emission of pollutants. Widespread
      human exposure to MTBE may occur due to leakage of gasoline storage tanks and a
      high stability and mobility of MTBE in ground water. To compare disposition of
      MTBE after different routes of exposure, its biotransformation was studied in
      humans after oral administration in water. Human volunteers (3 males and 3
      females, identical individuals, exposures were performed 4 weeks apart) were
      exposed to 5 and 15 mg 13C-MTBE dissolved in 100 ml of water. Urine samples from
      the volunteers were collected for 96 h after administration in 6-h intervals and
      blood samples were taken in intervals for 24 h. In urine, MTBE and the MTBE
      metabolites tert-butanol (t-butanol), 2-methyl-1,2-propane diol, and 2
      hydroxyisobutyrate were quantified, MTBE and t-butanol were determined in blood
      samples and in exhaled air in a limited study of 3 male volunteers given 15 mg
      MTBE in 100 ml of water. MTBE blood concentrations were 0.69 +/- 0.25 microM
      after 15 mg MTBE and 0.10 +/- 0.03 microM after 5 mg MTBE. MTBE was rapidly
      cleared from blood with terminal half-lives of 3.7 +/- 0.9 h (15 mg MTBE) and 8.1
      +/- 3.0 h (5 mg MTBE). The blood concentrations of t-butanol were 1.82 +/- 0.63
      microM after 15 mg MTBE and 0.45 +/- 0.13 microM after 5 mg MTBE. Approximately
      30% of the MTBE dose was cleared by exhalation as unchanged MTBE and as t
      butanol. MTBE exhalation was rapid and maximal MTBE concentrations (100 nmol/l)
      in exhaled air were achieved within 10-20 min. Clearance of MTBE by exhalation
      paralleled clearance of MTBE from blood. T-butanol was cleared from blood with
      half-lives of 8.5 +/- 2.4 h (15 mg MTBE) and 8.1 +/- 1.6 h (5 mg MTBE). In urine
      samples, 2-hydroxyisobutyrate was recovered as major excretory product, t-butanol
      and 2-methyl-1,2-propane diol were minor metabolites. Elimination half-lives for
      the different urinary metabolites of MTBE were between 7.7 and 17.8 h.
      Approximately 50% of the administered MTBE was recovered in urine of the
      volunteers after both exposures, another 30% was recovered in exhaled air as
      unchanged MTBE and t-butanol. The obtained data indicate that MTBE
      biotransformation and excretion after oral exposure is similar to inhalation
      exposure and suggest the absence of a significant first-pass metabolism of MTBE
      in the liver after oral administration.

PMID- 11294976
TI  - Pharmacologic, but not dietary, genistein supports endometriosis in a rat model.
AB  - Endometriosis is a disease in which uterine tissue proliferates in extrauterine
      sites. Using a surgical model to simulate endometriosis, we explored the
      potential for the phytoestrogen genistein, by injection and diet, to sustain
      endometriosis in rats. Uterine tissue was attached to intestinal mesentery of 8
      week-old Sprague Dawley rats. After 3 weeks, the rats were ovariectomized and the
      implants measured. Following 3 weeks of daily injections or exposure to dietary
      genistein, animals were necropsied and implants located and measured. Injections
      of genistein (50 and 16.6 microg/g BW) or estrone (1 microg/rat) sustained the
      implants; injection of sesame oil (vehicle for estrone), dimethylsulfoxide (DMSO;
      vehicle for genistein), or genistein at 5.0 microg/g BW did not sustain implants.
      Dietary genistein (250 or 1000 mg genistein/kg AIN-76A diet) did not support the
      implants. In ovary-intact rats exposed to 250 mg genistein/kg AIN-76A diet,
      implant size was not altered, compared to control-fed animals. To assess
      estrogenic actions of genistein, we measured uterine estrogen receptor alpha (ER
      alpha) and progesterone receptor (PR) isoforms A and B by Western blot analyses.
      Injections of estrone or genistein (50 or 16.6 microg/g BW) significantly reduced
      uterine ER-alpha compared to vehicle-treated animals. PR (B) was significantly
      increased by all injected doses of genistein or estrone and by the higher dietary
      dose (1000 mg genistein/kg AIN-76A). PR (A) was significantly increased by
      injected doses of genistein (16.6 and 5.0 microg/g BW). We conclude that
      pharmacologic injections, but not dietary physiological concentrations of
      genistein, support surgically induced endometriosis in rats. Our results suggest
      a critical role for ER modulation and genistein bioavailability in the
      maintenance of the implants.

PMID- 11294977
TI  - Effects of short-term in vivo exposure to polybrominated diphenyl ethers on
      thyroid hormones and hepatic enzyme activities in weanling rats.
AB  - Polybrominated diphenyl ethers (PBDEs), used as flame retardants, are ubiquitous
      environmental contaminants. PBDEs act as endocrine disruptors via alterations in
      thyroid hormone homeostasis. We examined thyroid hormone concentrations and
      hepatic enzyme activity in weanling rats exposed to three commercial PBDE
      mixtures: DE-71, DE-79, and DE-83R. Female Long-Evans rats, 28 days old, were
      orally administered various doses of DE-71, DE-79, or DE-83R for 4 days. Serum
      and liver samples were collected 24 h after the last dose and analyzed for serum
      total thyroxine (T(4)), triiodothyronine (T(3)), thyroid-stimulating hormone
      (TSH), hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and
      PROD), and uridinediphosphate-glucuronosyltransferase (UDPGT) activities. The
      PBDE-treated groups did not exhibit significant changes in body weight; however,
      increased liver weights, as well as 10- to 20-fold induction in EROD and 30- to
      40-fold induction in PROD were found in the DE-71-- and DE-79--treated animals.
      DE-71 and DE-79 caused dose-dependent depletion of T(4), accompanied by up to 3-
      to 4-fold induction in UDPGT activities. Serum total T(4) was decreased a maximum
      of 80% for DE-71 and 70% for DE-79 in the highest dose, with benchmark doses
      (BMDs) of approximately 12.74 mg/kg/day for DE-71 and 9.25 mg/kg/day for DE-79.
      Dose-related effects in serum T(3) levels were less apparent, with maximal
      reductions of 25-30% at the highest dose for both DE-71 and DE-79. The two
      mixtures showed no effect on serum TSH levels. Benchmark dose analysis revealed
      that the two mixtures were comparable in altering thyroid hormone levels and
      hepatic enzyme activity. DE-83R was not effective in altering any of the measured
      parameters. The present study suggests that short-term exposure to some
      commercial PBDE mixtures interferes with the thyroid hormone system via
      upregulation of UDPGTS:

PMID- 11294978
TI  - Fluoride-induced apoptosis in epithelial lung cells involves activation of MAP
      kinases p38 and possibly JNK.
AB  - Exposure to fluorides can induce inflammatory reactions, cell cycle arrest, and
      apoptosis in different experimental systems. Fluorides are known G-protein
      activators, but less is known about fluoride effects downstream of G-protein
      activation. The aim of this study was to elucidate whether the induction of
      apoptosis by fluorides and inhibition of proliferation is mediated by MAP kinases
      in primary rat lung, alveolar type 2 cells and the human epithelial lung cell
      line A549. Sodium fluoride (NaF) induced apoptosis in both cell types but at
      different concentrations, with the primary cells being more sensitive to NAF:
      Proliferation of the type 2 cells and A549 cells was inhibited in the presence of
      NAF: NaF induced a prolonged activation of MAP kinase ERK. NaF also activated p38
      and JNK in A549 cells for several hours (maximally 6-fold and 3-fold increase,
      respectively). Inhibition of ERK with the MEK1,2 inhibitor PD98059 increased
      apoptosis 2-fold, whereas the inhibitor of p38, SB202190, decreased the level of
      apoptotic cells by approximately 40%. SB202190 also inhibited apoptosis by almost
      40% when ERK activity was reduced in the presence of PD98059. Neither PD98059 nor
      SB202190 did affect the NaF-induced inhibition of proliferation. These
      observations indicate that activation of MAP kinases p38 and possibly JNK are
      involved in NaF-induced apoptosis of epithelial lung cells, whereas ERK
      activation seems to counteract apoptosis in epithelial lung cells. In contrast,
      activation of ERK and p38 are not involved in NaF-induced inhibition of cell
      proliferation.

PMID- 11294979
TI  - DNA damage induced by red food dyes orally administered to pregnant and male
      mice.
AB  - We determined the genotoxicity of synthetic red tar dyes currently used as food
      color additives in many countries, including JAPAN: For the preliminary
      assessment, we treated groups of 4 pregnant mice (gestational day 11) once orally
      at the limit dose (2000 mg/kg) of amaranth (food red No. 2), allura red (food red
      No. 40), or acid red (food red No. 106), and we sampled brain, lung, liver,
      kidney, glandular stomach, colon, urinary bladder, and embryo 3, 6, and 24 h
      after treatment. We used the comet (alkaline single cell gel electrophoresis)
      assay to measure DNA damage. The assay was positive in the colon 3 h after the
      administration of amaranth and allura red and weakly positive in the lung 6 h
      after the administration of amaranth. Acid red did not induce DNA damage in any
      sample at any sampling time. None of the dyes damaged DNA in other organs or the
      embryo. We then tested male mice with amaranth, allura red, and a related color
      additive, new coccine (food red No. 18). The 3 dyes induced DNA damage in the
      colon starting at 10 mg/kg. Twenty ml/kg of soaking liquid from commercial red
      ginger pickles, which contained 6.5 mg/10 ml of new coccine, induced DNA damage
      in colon, glandular stomach, and bladder. The potencies were compared to those of
      other rodent carcinogens. The rodent hepatocarcinogen p-dimethylaminoazobenzene
      induced colon DNA damage at 1 mg/kg, whereas it damaged liver DNA only at 500
      mg/kg. Although 1 mg/kg of N-nitrosodimethylamine induced DNA damage in liver and
      bladder, it did not induce colon DNA damage. N-nitrosodiethylamine at 14 mg/kg
      did not induce DNA damage in any organs examined. Because the 3 azo additives we
      examined induced colon DNA damage at a very low dose, more extensive assessment
      of azo additives is warranted.

PMID- 11294980
TI  - Neurotoxicity of the organochlorine insecticide heptachlor to murine striatal
      dopaminergic pathways.
AB  - Changes in biochemical status of nerve terminals in the corpus striatum, one of
      the primary brain regions affected in Parkinson's disease, were studied in groups
      of C57BL/6 mice treated by ip injection three times over a 2-week period with 3-
      100 mg/kg heptachlor. On average, the maximal rate of striatal dopamine uptake
      increased > 2-fold in mice treated at doses of 6 mg/kg heptachlor and 1.7-fold at
      12 mg/kg heptachlor. Increases in maximal rate of striatal dopamine uptake were
      attributed to induction of the dopamine transporter (DAT) and a compensatory
      response to elevated synaptic levels of dopamine. Significant increase in V(max)
      of striatal DAT was not observed at doses > 12 mg/kg, which suggested that toxic
      effects of heptachlor epoxide may be responsible for loss of maximal dopamine
      uptake observed at higher doses of heptachlor. In support of this conclusion,
      polarigraphic measurements of basal synaptosomal respiration rates from mice
      treated with doses of heptachlor > 25 mg/kg indicated marked, dose-dependent
      depression of basal tissue respiration. At doses of 6 and 12 mg/kg heptachlor,
      which increased expression of striatal DAT, uptake of 5-hydroxytryptamine into
      cortical synaptosomes was unaffected. Thus, striatal dopaminergic nerve terminals
      were found to be differentially sensitive to heptachlor. This reduced sensitivity
      of serotonergic pathways was mirrored in the greater potency of heptachlor
      epoxide to cause release of dopamine from preloaded striatal synaptosomes in
      vitro compared to release of serotonin from cortical membranes. These results
      suggest that heptachlor, and perhaps other organochlorine insecticides, exert
      selective effects on striatal dopaminergic neurons and may play a role in the
      etiology of idiopathic Parkinson's disease.

PMID- 11294981
TI  - Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal
      fluid: effect of lead exposure.
AB  - Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a
      role in transport of thyroid hormones in the brain. Our previous studies in
      animals suggest that sequestration of lead (Pb) in the choroid plexus may lead to
      a marked decrease in TTR levels in the cerebrospinal fluid (CSF). The objectives
      of this study were to establish in humans whether TTR and thyroxine (T(4)) are
      correlated in the CSF, and whether CSF levels of Pb are associated with those of
      TTR, T(4), and/or retinol-binding protein (RBP). Eighty-two paired CSF and
      blood/serum samples were collected from patients undergoing clinical diagnosis of
      CSF chemistry. Results showed that the mean value of CSF concentrations for TTR
      was 3.33 +/- 1.60 microg/mg of CSF proteins (mean +/- SD, n = 82), for total T(4)
      (TT(4)) was 1.56 +/- 1.68 ng/mg (n = 82), for RBP was 0.34 +/- 0.19 microg/mg (n
      = 82), and for Pb was 0.53 +/- 0.69 microg/dl (n = 61 for those above the
      detection limit). Linear regression analyses revealed that CSF TTR levels were
      positively associated with those of CSF TT(4) (r = 0.33, p < 0.005). CSF TTR
      concentrations, however, were inversely associated with CSF Pb concentrations (r
      = -0.29, p < 0.05). There was an inverse, albeit weak, correlation between CSF
      TT(4) and CSF Pb concentrations (r = -0.22, p = 0.09). The concentrations of TTR,
      TT(4), and Pb in the CSF did not vary as the function of their levels in blood or
      serum, but RBP concentrations in the CSF did correlate to those of serum (r =
      0.39, p < 0.0005). Unlike TTR, CSF RBP concentrations were not influenced by PB:
      These human data are consistent with our earlier observations in animals, which
      suggest that TTR is required for thyroxine transport in the CSF and that Pb
      exposure is likely associated with diminished TTR levels in the CSF.

PMID- 11294982
TI  - Effect of rodent diets on the sexual development of the rat.
AB  - Five rodent diets have been evaluated for their possible effect on the sexual
      development of the rat. Groups of 12 pregnant Alpk rats were fed one of the
      following combinations of diets during pregnancy and postnatally: RM3/RM1, AIN
      76A/AIN-76A, RM3/AIN-76A, Teklad Global 2016 (Global)/Global and Purina
      5001/Purina 5001. AIN-76A is phytoestrogen-free while the other diets contained
      varying amounts of phytoestrogens. The phytoestrogens genistein and daidzein were
      determined in the diets studied, and the concentrations found agreed with earlier
      estimates. RM3/RM1 was selected as the control group, as this has been used
      routinely in this laboratory for the past decade. Determinations were made in
      offspring of the times of vaginal opening and first estrus among the females, and
      of prepuce separation and testes descent among the males. At postnatal day (PND)
      26 the females from 6 of the 12 litters were terminated and tissue weights
      measured. Males from 6 of the 12 litters were similarly studied at PND 68.
      Animals from the remaining litters were transferred to RM1 diet at PND 70.
      Termination of the study was at PND 128 (males) and PND 140 (females) when body
      weights and tissue weights were determined. Marked differences in body weight,
      sexual development, and reproductive tissue weights were observed for rats
      maintained on AIN-76A or Purina 5001, with only minimal effects among rats
      maintained on the Global diet. These comparisons were against RM3/RM1 as the
      reference diet. However, using Purina 5001 as the reference diet reversed the
      direction of the differences seen when using RM3/RM1 as the reference diet. The
      differences observed when using RM3/RM1 as reference diet occurred mainly
      postnatally. In addition, the fact that similar differences were seen for the
      phytoestrogen-free diet, AIN-76A, and the phytoestrogen-rich diet, Purina 5001,
      indicate that these effects are more likely to be caused by nutritional
      differences between the diets that then have centrally mediated effects on rodent
      sexual development, rather than individual dietary components affecting
      peripheral estrogen receptors (ER). This proposal is supported by abolition of
      the uterotrophic activity of AIN-76A and Purina 5001 (relative to RM3/RM1) in the
      immature rat by coadministration of the gonadotrophin-releasing hormone (GnRH)
      antagonist ANTARELIX: The present data indicate that choice of diet may influence
      the timing of sexual development in the rat, and consequently, that when
      evaluating the potential endocrine toxicity of chemicals, the components of
      rodent diets used should be known, and as far as is possible, controlled.

PMID- 11294983
TI  - Repeated analysis of semen parameters in beagle dogs during a 2-year study with
      the HMG-CoA reductase inhibitor, atorvastatin.
AB  - Sperm analyses are often incorporated into reproductive toxicity studies in rats.
      Due to the relative ease of collecting multiple samples throughout a study, semen
      analysis in non-rodents such as dogs offers the opportunity to assess potential
      development of functional effects of compounds on male reproduction over time. In
      the present study, semen parameters were evaluated in beagle dogs during and at
      termination of a chronic toxicity study with the 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin. Male dogs received 0, 10,
      40, or 120 mg/kg orally in gelatin capsules for up to 104 weeks (n = 10/group).
      After 52 weeks of dosing, 3 dogs/group were euthanized, and 2/group were
      withdrawn from treatment for a 12-week reversal period and euthanized at Week 64.
      The remaining 5/group continued treatment until Week 104. Semen was collected
      from all animals for 3 consecutive weeks prior to termination of the 52-week
      animals (Weeks 50, 51, 52) for analysis of sperm parameters, using manual methods
      of evaluation. Semen was collected from the remaining animals at Weeks 64, 78,
      91, and 104, and was analyzed. At necropsy, testes, epididymides, and prostates
      were weighed and evaluated histologically, and epididymal sperm counts were
      determined. Serum cholesterol was decreased 25--60% at all doses during the
      study. There were no drug-related differences in semen volume and color, total
      sperm count, and sperm concentration, morphology, progressiveness, and percent
      motility during treatment with atorvastatin. There were also no effects on
      reproductive organ weights or histopathology, and no effects on epididymal sperm
      count. Thus, incorporation of semen analyses into this study allowed the
      evaluation of potential male reproductive effects in dogs at multiple time points
      during the study. Statistical power calculations demonstrated acceptable
      statistical power (> 80%) for semen sperm count, concentration, morphology, and
      motility with group sizes of 8--10 animals, and for semen sperm count and
      concentration or epididymal sperm count with group sizes of 3--5 animals, using
      the methodology described in this paper.

PMID- 11294984
TI  - Comparative pulmonary toxicity of 6 abrasive blasting agents.
AB  - Inhalation of silica dust is associated with pulmonary fibrosis. Therefore,
      substitute abrasive materials have been suggested for use in abrasive blasting
      operations. To date, toxicological evaluation of most substitute abrasives has
      been incomplete. Therefore, the objective of this study was to compare the
      pulmonary toxicity of a set of substitute abrasives (garnet, staurolite, coal
      slag, specular hematite, and treated sand) to that of blasting sand. Rats were
      exposed to blasting sand or an abrasive substitute by intratracheal instillation
      and pulmonary responses to exposure were monitored 4 weeks postexposure.
      Pulmonary damage was monitored as lactate dehydrogenase (LDH) in the acellular
      lavage fluid. Pulmonary inflammation was evaluated from the yield of
      polymorphonuclear leukocytes (PMN) obtained by bronchoalveolar lavage. The
      activity of alveolar macrophages was determined by measuring zymosan-stimulated
      chemiluminescence. Blasting sand caused lung damage and showed histologic
      evidence for inflammation and fibrosis. Garnet, staurolite, and treated sand
      exhibited toxicity and inflammation that were similar to blasting sand, while
      coal slag caused greater pulmonary damage and inflammation than blasting sand. In
      contrast, specular hematite did not significantly elevate LDH or PMN levels and
      did not stimulate macrophage activity 4 weeks postexposure.

PMID- 11294985
TI  - Residual oil fly ash inhalation in guinea pigs: influence of absorbate and
      glutathione depletion.
AB  - Inhaled urban particulate matter (PM) often contains metals that appear to
      contribute to its toxicity. These particles first make contact with a thin layer
      of epithelial lining fluid in the respiratory tract. Antioxidants present in this
      fluid and in cells might be important susceptibility factors in PM toxicity. We
      investigated the role of ascorbic acid (C) and glutathione (GSH) as determinants
      of susceptibility to inhaled residual oil fly ash (ROFA) in guinea pigs (male,
      Hartley). Guinea pigs were divided into four groups, +C+GSH, +C-GSH, -C+GSH, and 
      C-GSH, and exposed to clean air or ROFA (< 2.5 micron diameter, 19--25 mg/m(3)
      nose-only for 2.0 h). C and/or GSH were lowered by either feeding C-depleted diet
      (1 microg C/kg diet, 2 weeks) and/or by ip injection of a mixture of buthionine
      S,R-sulfoximine (2.7 mmol/kg body weight) and diethylmaleate (1.2 mmol/kg, 2 h
      prior). Nasal lavage (NL) and bronchoalveolar lavage (BAL) fluid and cells were
      examined at 0 h and 24 h postexposure to ROFA. The C-deficient diet lowered C
      concentrations in BAL fluid and cells and in NL fluid by 90%, and the GSH
      depletion regimen lowered both GSH and C in the BAL fluid and cells by 50%. ROFA
      deposition was calculated at time 0 from lung Ni levels to be 46 microg/g wet
      lung. In unexposed animals, the combined deficiency of C and GSH modified the
      cellular composition of cells recovered in lavage fluid, i.e., the increased
      number of eosinophils and macrophages in BAL fluid. ROFA inhalation increased
      lung injury in the -C-GSH group only (evidenced by increased BAL protein, LDH and
      neutrophils, and decreased BAL macrophages). ROFA exposure decreased C in BAL and
      NL at 0 h, and increased BAL C and GSH (2- to 4-fold above normal) at 24 h in
      nondepleted guinea pigs, but had no effect on C and GSH in depleted guinea pigs.
      Combined deficiency of C and GSH resulted in the highest macrophage and
      eosinophil counts of any group. GSH depletion was associated with increased BAL
      protein and LDH, increased numbers of BAL macrophages and eosinophils, and
      decreased rectal body temperatures. We conclude that combined deficiency of C and
      GSH increased susceptibility to inhaled ROFA; caused unusual BAL cellular
      changes; resulted in lower antioxidant concentrations in BAL than were observed
      with single deficiencies. Antioxidant deficiency may explain increased
      susceptibility to PM in elderly or diseased populations and may have important
      implications for extrapolating animal toxicity data to humans.

PMID- 11294986
TI  - Gene expression profiling of cultured human bronchial epithelial and lung
      carcinoma cells.
AB  - Lung cancer is a complex collection of diseases that is thought to begin with
      single mutated progenitor cells and culminates in any of several clinically
      described pathologies. Our knowledge of the molecular events that lead to
      different lung cancer types--small cell carcinoma, squamous cell carcinoma,
      adenocarcinoma, and large cell carcinoma--is incomplete. Nonetheless, it is
      evident that genetic changes that impact multiple molecular networks are involved
      in the generation of each specific phenotype. Due to the obvious complexity of
      these processes, the simultaneous quantitative monitoring of changes in the
      expression of genes that define these networks can provide mechanistic
      information to increase our understanding of the molecular basis for human
      pulmonary carcinogenesis. To this end, we have employed a commercially available
      human cDNA array (Atlas Human Array, Clontech Laboratories) to systematically
      screen for alterations in the expression of 600 genes in normal human bronchial
      epithelial (NHBE) cells as well as in several lung carcinoma lines. Studies on
      the reproducibility and variability of array results indicate that a 2-fold or
      greater difference in the expression of a particular gene could be considered a
      real difference in transcript abundance. Accuracy of gene expression as measured
      in the array was verified by comparing mRNA levels of the proto-oncogene c-myc in
      the array with results obtained by traditional Northern blot analysis and by
      quantitative RT-PCR. Gene expression profiles were compared within and among cell
      types. The differential expression of 17 genes, including downregulation of MRP8
      and MRP14 and upregulation of CYP1B1, was observed in all four carcinoma lines
      compared to NHBE cells. The direction of all 17 gene expression differences,
      either upregulation or downregulation relative to NHBE cells, was the same for
      all four carcinoma lines, underscoring their common molecular features. Each lung
      tumor line also exhibited a number of unique differences compared to both normal
      cells and the other tumor cell lines. These differences may be due to differences
      in the cellular origin and/or pathology of the cell lines studied.

PMID- 11294987
TI  - The effects of perinatal/juvenile heptachlor exposure on adult immune and
      reproductive system function in rats.
AB  - This study was performed to determine if developmental exposure of rats to
      heptachlor (H) during the last half of gestation through puberty adversely
      affects adult functioning of the immune and reproductive systems. Time-bred
      pregnant female Sprague-Dawley rats were dosed by gavage with H (0, 30, 300, or
      3000 microg/kg/day) from gestation day (GD) 12 to postnatal day (PND) 7, followed
      by direct dosing of the pups with H through PND 42. Separate groups of rats were
      evaluated with a battery of immune function tests, while other groups of rats
      were evaluated for reproductive development and function. Additional groups of
      rats were euthanized at the end of the dosing period for histological analyses of
      major organ systems. Some dams and PND 7 pups were euthanized; milk, plasma, fat
      and/or tissues were assayed for H and heptachlor epoxide B (HEB), a major
      metabolite of H. The amount of H and HEB found in milk, blood, fat, and tissues
      was proportional to the dose of H administered. There were no effects on the
      number or survival of pups born to H-exposed dams nor to pups exposed
      postnatally. There were no effects on the number of treated dams delivering
      litters or on litter size, nor were there any effects on any of the reproductive
      end points examined in the F(0) or F(1) rats. There were no effects of H exposure
      on lymphoid organ weights, splenic natural killer (NK) cell activity, and splenic
      lymphoproliferative (LP) responses to mitogens and allogeneic cells in a mixed
      lymphocyte response (MLR) assay at 8 weeks of age. H exposure did not alter
      delayed or contact hypersensitivity at 10 or 17 weeks of age, respectively.
      However, the primary IgM antibody response to sheep red blood cells (SRBCs) was
      suppressed in a dose-dependent manner in males, but not females, at 8 weeks of
      age. The percentage of B lymphocytes (OX12(+)OX19(-)) in spleen was also reduced
      in the high-dose males. The anti-SRBC IgM response was reduced only in males
      exposed to 30 microg H/kg/day in a separate group of rats 21 weeks of age. In
      these same rats, at 26 weeks of age, the secondary IgG antibody response to SRBCs
      was suppressed in all of the H-exposed males, but not females. These data
      indicate that perinatal exposure of male rats to H results in suppression of the
      primary IgM and secondary IgG anti-SRBC responses. Suppression of these antibody
      responses persisted for up to 20 weeks after the last exposure to H, at a total
      exposure of approximately 1500 microg H/kg/rat.

PMID- 11294988
TI  - alpha 2u-Globulin nephropathy, renal cell proliferation, and dosimetry of inhaled
      tert-butyl alcohol in male and female F-344 rats.
AB  - tert-Butyl alcohol (TBA) has been shown to cause kidney tumors in male rats
      following chronic administration in drinking water. The objective of the present
      study was to determine whether TBA induces alpha 2u-globulin (alpha 2u)
      nephropathy (alpha 2u-N) and enhanced renal cell proliferation in male, but not
      female, F-344 rats, and whether the dosimetry of TBA to the kidney is gender
      specific. Male and female F-344 rats were exposed to 0, 250, 450, or 1750 ppm TBA
      vapors 6 h/day for 10 consecutive days to assess alpha 2u-nephropathy and renal
      cell proliferation and for 1 and 8 days to evaluate the dosimetry of TBA
      following a single and repeated exposure scenario. Protein droplet accumulation
      was observed in kidneys of male rats exposed to 1750 ppm TBA, with alpha 2u
      globulin immunoreactivity present in these protein droplets. A statistically
      significant increase in alpha 2u concentration in the kidney, as measured by an
      enzyme-linked immunosorbent assay, was observed in male rats exposed to 1750 ppm
      TBA with a exposure-related increase in renal cell proliferation. Renal alpha 2u
      concentration was positively correlated with cell proliferation in male rat
      kidney. No histological lesions or increased renal cell proliferation was
      observed in female rats exposed to TBA compared to controls. The TBA kidney:blood
      ratio was higher at all concentrations and time points in male rats compared with
      female rats, which suggests that TBA is retained longer in male rat kidney
      compared with female rat kidney. Together these data suggest that TBA causes
      alpha 2u-N in male rats, which is responsible for the male rat-specific increase
      in renal cell proliferation.

PMID- 11294989
TI  - Correlation of cardiotoxicity mediated by halogenated aromatic hydrocarbons to
      aryl hydrocarbon receptor activation.
AB  - In mammals, the toxicity of halogenated aromatic hydrocarbons (HAH) correlates
      with their ability to activate the aryl hydrocarbon receptor (AHR). To test this
      correlation in an avian model, we selected six HAHs based on their affinity for
      the mammalian AHR, including: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD);
      1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD); 2,3,7,8-tetrachlorodibenzofuran
      (TCDF); 2,3,4,7,8-pentachlorodibenzofuran (PCDF); 3,3',4,4'-tetrachlorobiphenyl
      (PCB 77); and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153). We determined the
      ability of these compounds to induce cardiotoxicity, as measured by an increase
      in heart wet weight on incubation day 10 in the chick embryo (Gallus gallus) and
      formation of the avian AHR/ARNT/DNA binding complex in chicken hepatoma cells.
      Relative potency values (RPs) were calculated by dividing the TCDD EC(50)
      (AHR/ARNT/DNA binding) or ED(50) (15% increase in day-10 heart wet weight) by the
      HAH congeners EC(50) or ED(50), respectively. The rank order of potencies for
      inducing cardiotoxicity were TCDD > PCDD = PCDF = TCDF > PCDF > PCB77, PCB 153,
      no effect. The RP values for inducing AHR/ARNT DNA binding were then correlated
      with those for inducing cardiotoxicity (the RP values of PCDD were determined to
      be statistical outliers). This correlation was found to be highly significant (r
      = 0.94, p = 0.017). The ability of PCDD to act as an AHR agonist was verified
      using luciferase reporter assays and analysis of cytochrome P4501A1 protein
      levels. These results indicate that the ability of HAHs to activate the avian AHR
      signaling pathway, in general, correlates with their ability to mediate
      cardiotoxicity in the chick embryo.

PMID- 11294990
TI  - Neuropathology associated with ventricular assist devices: an autopsy series of
      33 patients.
AB  - The ventricular assist device (VAD) is a mechanical pump that has been shown to
      be an effective modality of cardiac support in patients with heart failure
      refractory to pharmacologic intervention and who are awaiting cardiac allograft
      transplantation. Neuropathologic findings in these patients have not been well
      described. We retrospectively reviewed 2,632 autopsy reports (between 1990 and
      2000) and found 64 patients who received VADs. Of these 64 patients, brain and
      spinal cord tissue was available for review in 33 patients (25 males and eight
      females; age range, 4 to 69 years; mean age, 52 years). The study group was
      composed of these 33 patients. Ventricular assist devices were in place from one
      to 603 days (mean 49 days). Twenty-five patients had left VAD, three had right
      VAD, and five had biventricular VADs. Brain weights ranged from 928 g to 1,740 g
      (mean 1,325 g). The most common central nervous system pathologic findings
      included infarct (N = 23; 70%), acute neuronal necrosis (N = 22; 67% focal and N
      = 1; diffuse anoxic encephalopathy), hemorrhage (N = 14; 42%), and herniations (N
      = 7; 21%). Two patients had no neuropathologic findings at autopsy. Cause of
      death was central nervous system-related in eight patients (24%) including six
      with massive parenchymal hemorrhage and herniations, one with brainstem
      infarction, and one with air embolism (radiographically diagnosed). The most
      common causes of death in the remaining 25 patients included sepsis (n = 10;
      30%), pneumonia (n = 4; 12%), and embolic events with widespread infarcts (n = 4;
      12%). The most common neuropathologic findings in patients with VAD were related
      to ischemia and infarction. In a significant subset of patients, central nervous
      system pathology, particularly hemorrhage with herniation, was the primary cause
      of death. Ann Diagn Pathol 5:67-73, 2001.

PMID- 11294991
TI  - Pulmonary granular cell tumor coexisting with bronchogenic carcinoma.
AB  - Pulmonary granular cell tumors (GCTs) are uncommon and predominantly benign. The
      coexistence of GCTs with bronchogenic carcinoma is rare. We report three cases of
      GCT occurring simultaneously with a primary bronchogenic carcinoma. In one case
      mucoepidermoid carcinoma was seen colliding with a bronchial submucosal GCT. In
      another case an endobronchial GCT was seen beneath squamous cell carcinoma in
      situ and adjacent to invasive squamous carcinoma. In the third case a central
      bronchial GCT was identified concurrently with a peripheral adenocarcinoma. We
      suggest that the presence of a GCT should prompt adequate sampling to rule out
      the coexistence of bronchogenic carcinoma. Clinical awareness and complete
      evaluation for a malignant primary lung tumor will lead to more appropriate
      therapy. Ann Diagn Pathol 5:74-79, 2001.

PMID- 11294992
TI  - Hemangioma of the testis: report of unusual occurrences of cavernous hemangioma
      in a fetus and capillary hemangioma in an older man.
AB  - We report two cases of hemangiomata of the testes which occurred in a 17-week-old
      fetus and a 73-year-old man. To our knowledge, these are the first reported cases
      of cavernous hemangioma of the testis in a fetus and capillary hemangioma of the
      testis in an older man. Although a hemangioma of the testis is rare, it should be
      considered in the differential diagnosis of a testicular tumor. Ann Diagn Pathol
      5:80-83, 2001.

PMID- 11294993
TI  - Diagnostic value of immunohistochemically detected surfactant--apoprotein-A in
      malignant tumors located in the lungs: report of two cases.
AB  - We report two cases of patients suffering from multiple tumors in the lungs with
      questionable origin. In these cases, the expression of Surfactant-apoprotein-A
      (SP-A) by the tumor cells has been a helpful feature in the process of diagnosis
      by indicating primary carcinomas of the lungs. Surfactant-apoprotein-A is
      expressed by the pneumocytes II in lung tissue and a portion of non-small cell
      lung carcinomas and has not yet been found to be expressed by other tumors when
      detected immunohistochemically by use of the monoclonal antibody PE-10. We
      analyzed formalin-fixed, paraffin-embedded specimens of different malignancies
      with pulmonary location for the expression of SP-A by the use of PE-10 with other
      antibodies against additional epitopes such as the thyroid transcription factor
      1. In normal lung areas a distinct staining of the pneumocytes II has been
      observed. All the control sections of primary and metastatic nonlung-carcinoma
      specimen in our study remained negative. The monoclonal antibody PE-10 used in
      this study provides high specificity when compared to the results obtained with
      polyclonal antibodies. One of the two cases reported, a mucinous carcinoma of the
      lungs, had been negative for thyroid transcription factor-1 but positive for SP
      A. Thus, SP-A detected by immunohistochemistry using the monoclonal antibody PE
      10, together with other parameters such as thyroid transcription factor-1, may be
      a useful tool for individual diagnosis of malignomas located in the lungs with a
      questionable primary origin. Ann Diagn Pathol 5:84-90, 2001.

PMID- 11294994
TI  - Pryce's type I pulmonary intralobar sequestration presenting with massive
      hemoptysis.
AB  - Pryce's type I intralobar sequestration, in which a region of lung exhibits
      tracheobronchial continuity and aberrant systemic arterial supply, is most
      frequently asymptomatic and discovered incidentally. While hemoptysis may be a
      common presenting symptom, massive hemoptysis is rarely seen. We document a case
      of a 58-year-old man, previously asymptomatic, whose initial presentation was
      that of massive hemoptysis. The radiographic, intraoperative and pathologic
      findings in our patient confirm that his sequestration was of Pryce's type I. Ann
      Diagn Pathol 5:91-95, 2001.

PMID- 11294995
TI  - A report of intracranial Rosai-Dorfman disease with literature review.
AB  - Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy), is a
      rare benign histiocytic proliferative disorder. Over 650 cases have been reported
      since 1969. To the best of our knowledge, there have been only 31 cases with
      central nervous system involvement reported in the literature. Intracranial
      disease usually presents clinically and radiologically as a "meningioma". It can
      be misdiagnosed as a nonspecific inflammatory process because of the atypical
      histologic features of Rosai-Dorfman disease occurring in a non-nodal location.
      Familiarity with such atypical histologic features and appropriate use of
      immunohistochemical stains is required for a definitive diagnosis of central
      nervous system Rosai-Dorfman disease. We report such an intracranial lesion with
      other extranodal sites of involvement with a 5-year follow up and a review of
      previously reported cases. Ann Diagn Pathol 5:96-102, 2001.

PMID- 11294996
TI  - Intravascular lymphomatosis presenting within angiolipomas.
AB  - This report presents a case of intravascular lymphomatosis identified within an
      angiolipoma. The patient was a 73-year-old woman with a history of lobular
      carcinoma of the breast who presented with a chest wall nodule near the site of
      prior mastectomy. Microscopically, the nodule was composed of encapsulated
      adipose tissue with an associated vascular proliferation. Many of the vascular
      lumina were expanded by collections of large pleomorphic cells with vesicular
      nuclei and prominent nucleoli. These atypical cells displayed immunoreactivity
      for CD45RB (leukocyte common antigen) and the pan-B cell marker CD20 (L26). The
      patient subsequently developed multiple lesions of the extremities and died soon
      after developing symptoms referable to the central nervous system. Intravascular
      lymphomatosis most commonly presents with central nervous system and dermatologic
      involvement although any organ system may be affected. Intravascular
      lymphomatosis is an aggressive neoplasm that is generally diagnosed at postmortem
      examination. This case shows the protean manifestations of intravascular
      lymphomatosis and highlights the necessity of considering this malignancy in the
      differential diagnosis when entertaining the diagnosis of vascular invasion by
      carcinoma. Ann Diagn pathol 5:103-106, 2001. This is a US government work. There
      are no restrictions on its use.

PMID- 11294997
TI  - Agar specimen orientation technique revisited: a simple and effective method in
      histopathology.
AB  - The agar technique represents an important method to obtain optimal orientation
      of small specimens during paraffin embedding and to avoid tissue loss during
      processing. This method is advisable for ocular, temporal artery,
      gastrointestinal, cervical, and skin biopsies and may be applied with formalin
      fixed specimens as well as with fresh tissue. Microwave oven can be successfully
      used to make the small specimen orientation technique with agar quicker and
      easier. Ann Diagn Pathol 5:107-109, 2001.

PMID- 11294998
TI  - Topics in bone marrow biopsy pathology: role of marrow topography in
      myelodysplastic syndromes and evaluation of post-treatment and post-bone marrow
      transplant biopsies.
AB  - The role of bone marrow biopsy is expanding. Bone marrow biopsy is considered a
      "gold standard" for assessing cellularity and infiltrative process. More
      recently, biopsies are increasingly used for immunohistochemical stains and
      molecular studies such as in situ hybridization and laser microdissection,
      further augmenting morphologic interpretation. Biopsies are playing a greater
      role in early diagnosis of myelodysplastic syndromes (MDS). Both primary and
      secondary MDS are increasing (5% to 12%), and can present a significant challenge
      in early diagnosis. Present MDS diagnostic criteria are based purely on marrow
      aspirate smears, peripheral blood smears, and ancillary studies, and may not be
      adequate in some instances. With the current understanding of marrow topography
      and hematopoietic microenvironment, bone marrow biopsies are greatly useful in
      early diagnosis and grading of MDS. Marrow biopsies also are helpful in
      evaluation of postchemotherapy and post-bone marrow transplant patients.
      Assessment of topographic alteration and certain corroborating
      immunohistochemical and molecular studies can only be performed on bone marrow
      biopsies, and these ancillary studies will contribute significantly to the
      understanding of hematopoietic disorders. Bone marrow biopsy, in conjunction with
      other modalities such as flow cytometry, will play a significant role in
      diagnostic hematopathology. Ann Diagn Pathol 5:110-120, 2001.

PMID- 11294999
TI  - Samuel David Gross--America's first pathologist.

PMID- 11295000
TI  - The community integration measure: development and preliminary validation.
AB  - OBJECTIVE: To present a new measure of community integration, the Community
      Integration Measure (CIM), and to offer preliminary information about its
      psychometric properties. DESIGN: Validation study. SETTING: Community.
      PARTICIPANTS: Ninety-two participants placed in 3 subgroups (brain injury
      survivors, n = 41; significant others, n = 36; college students, n = 15). MAIN
      OUTCOME MEASURES: The distributional properties, factor structure, internal
      consistency reliability, content validity, discriminant validity, concurrent
      validity, and construct validity of the CIM. RESULTS: All items correlated
      positively with each other and with the total score. Principal components factor
      analysis confirmed a 1-factor structure, which explained 44.1% of the variance.
      Internal consistency reliability, using Cronbach's alpha, was.87. Content
      validity was assured by the development procedure, correspondence with the
      theoretical model, and direct use of consumer language. Discriminant validity was
      supported by the CIM's ability to differentiate between subsamples. Criterion
      validity was supported by using correlations with the Community Integration
      Questionnaire. Construct validity was supported by correlations with the
      Interpersonal Support Evaluation List. CONCLUSION: The CIM offers a brief, easily
      administered measure of community integration that conforms to an empirically
      derived theoretical model and is psychometrically sound.

PMID- 11295001
TI  - A comparison of acute and postdischarge predictors of employment 2 years after
      traumatic brain injury.
AB  - OBJECTIVE: To examine whether adding postdischarge psychosocial predictors to
      premorbid and injury-related variables improved the capacity to predict
      employment 2 years after rehabilitation for traumatic brain injury (TBI). DESIGN:
      Data were collected prospectively at 6 and 24 months after discharge from
      rehabilitation. Logistic regression analyses examined predictors of employment
      status. SETTING: Inpatient and community TBI rehabilitation service attached to a
      major Australian teaching hospital. PARTICIPANTS: Fifty-five patients with TBI,
      aged 16 or older, who were consecutively admitted to a brain injury unit with
      complete longitudinal data and who agreed to participate in the study.
      INTERVENTION: Measured injury severity (Glasgow Coma Scale scores, posttraumatic
      amnesia); functional independence (Functional Assessment Measure cognitive
      subscale) at admission and discharge from rehabilitation; self-report of
      employment (premorbid, postdischarge); postdischarge psychosocial status at 6
      months and 2 years (Community Integration Questionnaire, General Health
      Questionnaire, Trauma Complaints List, Overt Aggression Scale, Alcohol Use
      Disorders Inventory Test, Satisfaction with Life Scale). MAIN OUTCOME MEASURES:
      Employment status (employed, unemployed) was used to reflect vocational outcome.
      Predictor variables comprised premorbid work status, injury-related variables
      (age, injury severity), and postdischarge variables (employment, community
      integration, psychologic, cognitive status). RESULTS: Adding postdischarge
      predictors to premorbid and acute variables significantly improved the ability to
      predict work status 2 years after rehabilitation. Age at the time of injury,
      premorbid employment status, work status, and psychologic distress 6 months
      postdischarge were significant predictors of employment. CONCLUSIONS: It is
      important to consider postdischarge psychologic well-being, in conjunction with
      premorbid and acute factors, in vocational interventions after TBI.

PMID- 11295003
TI  - Efficacy of an energy conservation course for persons with multiple sclerosis.
AB  - OBJECTIVE: To evaluate the efficacy of an energy conservation course on fatigue
      impact, self-efficacy, and quality of life (QOL) for persons with multiple
      sclerosis (MS). DESIGN: Repeated measures with control and experimental
      interventions conducted during a 19-week study. SETTING: Community-based
      treatment center. PARTICIPANTS: A convenience sample of 54 individuals from 79
      community-dwelling volunteers with fatigue secondary to MS. INTERVENTION: A 6
      session, 2-hr/wk energy conservation course taught by occupational therapists for
      groups of 8 to 10 participants. MAIN OUTCOME MEASURES: Fatigue Impact Scale (self
      report measure of fatigue impact on cognitive, physical, social functions), Self
      Efficacy Gauge (self-report measure of confidence in ability to perform specific
      behaviors), and Medical Outcomes Study Short-Form Health Survey (QOL measure).
      RESULTS: Participants reported, as predicted, significantly less fatigue impact,
      increased self-efficacy, and improved QOL (ie, 3 of 4 subscales expected to
      improve). There were no significant differences, as predicted, in any of the
      dependent variables after the control (ie, support group) and no intervention
      periods. CONCLUSION: Results provide strong evidence for the efficacy of this
      energy conservation course for persons with MS.

PMID- 11295002
TI  - Transcutaneous electric nerve stimulation reduces neglect-related postural
      instability after stroke.
AB  - OBJECTIVE: To test the existence of a neglect-related component of postural
      imbalance in some stroke patients to determine whether neglect patients (1) show
      worse postural control compared with nonneglect patients and healthy subjects and
      (2) have latent postural capacities that could be unmasked by an appropriate
      somatosensory manipulation. DESIGN: Intervention study with and without
      transcutaneous electric nerve stimulation (TENS). SETTING: Rehabilitation center
      research laboratory. PARTICIPANTS: Twenty-two stroke patients (mean age, 58.3 +/-
      2.5yr; average days since stroke, 83.2d) and 14 age-matched healthy subjects.
      Stroke patients were subdivided into 3 groups: 6 with spatial neglect and 16
      without (8 with left lesion, 8 with right lesion). INTERVENTIONS: All
      participants were subjected to a dynamic balance task, performed while sitting
      for 8 seconds on a laterally rocking platform. Seated on this mobile support,
      they were asked to maintain actively an erect posture, sitting as still as
      possible. In patients, TENS was applied on the contralesional side of the neck
      during the postural task. An effective stimulation (intensity corresponding to
      the threshold of perception, TENS+) was compared with a placebo stimulation (.01
      x threshold of perception, TENS-). MAIN OUTCOME MEASURES: Postural performance in
      each trial was monitored by using 2 criteria: the number of aborted trials caused
      by loss of balance, and the angular dispersion of the support oscillations in
      roll. The latter criterion, which increased with body instability, was defined as
      2 standard deviations of the angular distribution. RESULTS: Patients showing
      neglect displayed pronounced postural instability compared with other patients
      and controls. Although dramatic postural instability in the neglect patients was
      spectacularly and systematically reduced with TENS, no effect was observed in
      patients without neglect. CONCLUSION: This is among the first studies to provide
      clinical evidence supporting the "postural body scheme" concept.

PMID- 11295004
TI  - Functional outcomes of persons with brain tumors after inpatient rehabilitation.
AB  - OBJECTIVE: To assess the extent of functional gains measured before and after
      inpatient rehabilitation in patients who have primary or metastatic brain tumors,
      and to identify whether the tumor type, recurrent tumor, or ongoing radiation
      influences outcomes. DESIGN: Retrospective, descriptive study. SETTING: A free
      standing university-affiliated rehabilitation hospital. PARTICIPANTS: A referred
      sample of 132 persons, all with functional impairments from a brain tumor and
      discharged from inpatient rehabilitation during a 3-year time period.
      INTERVENTION: Comprehensive inpatient rehabilitation. MAIN OUTCOME MEASURES:
      Functional status and rate of functional improvement (gain) as measured by the
      FIM instrument and FIM efficiency. RESULTS: Mean FIM efficiencies +/- standard
      deviation for motor (.82 +/-.69) and cognitive (.15 +/-.24) functions were
      equivalent across primary and metastatic tumor types (F =.42, df = 3,103, p = NS;
      F =.45, df = 2,104, p = NS, respectively); patients with metastatic disease had a
      significantly shorter length of stay at 18 +/- 12.3 days (t30,6 = 2.3, p =.03).
      Patients who received radiation during rehabilitation had a significantly greater
      (F = 4.1, df = 1,105, p <.05) motor efficiency score (1 +/-.79) than those who
      did not (.78 +/- 0.7). Patients with recurrent tumors made FIM cognitive changes
      equivalent to those of persons undergoing rehabilitation after their initial
      diagnosis, but their motor efficiency scores were significantly smaller (.55 +/
      .39 vs.98 +/-.68, respectively) (F = 5.77, df = 1,85, p =.018), which reflected a
      significantly smaller FIM motor change. CONCLUSIONS: Metastatic or primary brain
      tumor type does not affect the efficiency of functional improvement during
      inpatient rehabilitation. Patients receiving concurrent radiation therapy make
      greater functional improvement per day than those not receiving radiation.
      Patients with recurrent tumors make significantly smaller functional motor gains
      than those completing inpatient rehabilitation after the tumor's initial
      diagnosis.

PMID- 11295005
TI  - Functional mobility performance in an elderly population with lumbar spinal
      stenosis.
AB  - OBJECTIVES: To compare the functional mobility (FM) of elderly apparently healthy
      (AH) subjects and patients with lumbar spinal stenosis (LSS) and to evaluate the
      reliability and validity of the FM tests. DESIGN: Using the test-retest paradigm,
      FM performance was assessed in AH subjects. A single FM assessment was conducted
      on a group of LSS subjects. Between-group performance comparisons were made with
      the AH subjects and the LSS patients. SETTING: Orthopedic clinical practice (LSS
      subjects) and university laboratory (AH subjects). PARTICIPANTS: Fifty-seven
      patients seen in an orthopedic clinical practice for LSS and 96 AH subjects who
      were volunteers identified from among participants of The Lifelong Learning
      Society at Florida Atlantic University. INTERVENTIONS: Treadmill walk (TW) test
      (at 53.6 m/min, 1% increase in grade per min) until 70% of the predicted maximum
      heart rate was achieved or associated pain made participation uncomfortable.
      Three trials each of a sit-to-stand (SS, rise from chair as quickly as possible
      without using arms) and a weight-carrying (WC, walk 20 m as quickly as possible
      for time carrying 10% of the body weight evenly distributed in hand-held weights)
      test. The AH group repeated all tests on a separate day. MAIN OUTCOME MEASURES:
      Time to walk treadmill, stand from sitting position, walk 20 meters, and analysis
      of variance between groups. RESULTS: Significant between-group differences were
      found for the TW, SS, and WC tests. Test-retest r values of .839 for the TW, .848
      for the SS, and .833 for the WC were observed. CONCLUSIONS: The AH group
      demonstrated greater FM than the LSS group. The performance disparity between
      groups may suggest context validity, while the AH groups test-retest stability
      reflects reliability.

PMID- 11295006
TI  - Evaluation of dynamic balance among community-dwelling older adult fallers: a
      generalizability study of the limits of stability test.
AB  - OBJECTIVE: To establish reliability estimates of the 75% Limits of Stability Test
      (75% LOS test) when administered to community-dwelling older adults with a
      history of falls. DESIGN: Generalizability theory was used to estimate both the
      relative contribution of identified error sources to the total measurement error
      and generalizability coefficients. A random effects repeated-measures analysis of
      variance (ANOVA) was used to assess consistency of LOS test movement variables
      across both days and targets. SETTING: A motor control research laboratory in a
      university setting. PARTICIPANTS: Fifty community-dwelling older adults with 2 or
      more falls in the previous year. MAIN OUTCOME MEASURES: Spatial and temporal
      measures of dynamic balance derived from the 75% LOS test included average
      movement velocity, maximum center of gravity (COG) excursion, end-point COG
      excursion, and directional control. RESULTS: Estimated generalizability
      coefficients for 2 testing days ranged from.58 to.87. Total variance in LOS test
      measures attributable to inconsistencies in day-to-day test performance (Day and
      Subject x Day facets) ranged from 2.5% to 8.4%. The ANOVA results indicated that
      no significant differences were observed in the LOS test variables across the 2
      testing days. CONCLUSIONS: The 75% LOS test administered to older adult fallers
      on 2 consecutive days provides consistent and reliable measures of dynamic
      balance.

PMID- 11295007
TI  - Proactive balance strategy while maintaining a stationary wheelie.
AB  - OBJECTIVE: To test the hypothesis that a reactive balance strategy is used while
      maintaining a stationary wheelie, specifically that a forward pitch from the
      wheelie equilibrium position is associated with a forward displacement of the
      wheelchair and a rear pitch with rear displacement, with the displacement
      slightly after the change in pitch. DESIGN: Descriptive and quantitative
      kinematic analysis. SETTING: Kinesiologic laboratory. PARTICIPANTS: A convenience
      sample of 10 able-bodied adults. INTERVENTION: Subjects taught to pop and
      maintain a stationary wheelie for 15 seconds while remaining within a .75 x .75
      m2. Three trials of 5 seconds; digitized targets videotaped for analysis. MAIN
      OUTCOME MEASURES: Pitch angle and rear-wheel position of the wheelchair, derived
      from digitized videotape and time-series analysis of phase lag. RESULTS: There
      was an inverse relationship between the direction of pitch and linear
      displacement-rear pitch was associated with forward wheel displacement and
      forward pitch was associated with rearward wheel displacement. The mean pitch
      angle +/- standard deviation was 13.6 degrees +/- 2.3 degrees and the mean
      horizontal position of the wheelchair was 0.0 +/- 4.9cm. There was little or no
      phase lag between pitch and displacement. CONCLUSIONS: Wheelie performers
      maintaining a stationary wheelie appeared to use a proactive balance strategy, in
      which they used a functional base of support that was larger than the geometric
      one. These findings may have significance for those who are learning and teaching
      wheelies and provide broader insights into the nature of dynamic balance.

PMID- 11295008
TI  - Botulinum toxin for people with dystonia treated by an outreach nurse
      practitioner: a comparative study between a home and a clinic treatment service.
AB  - OBJECTIVE: To study whether a trained outreach nurse practitioner could provide a
      service that is as good as, or better than, that provided at a hospital
      outpatient clinic for people who had been diagnosed with dystonia and required
      treatment with botulinum toxin. DESIGN: Randomized trial. SETTING: An outpatient
      department of a regional neurorehabilitation center and patients' homes in
      northern England. PATIENTS: Eighty-nine patients with a clinical diagnosis of
      spasmodic torticollis, blepharospasm, or hemifacial spasm who had ongoing
      treatment of dystonia with botulinum injections. INTERVENTIONS: Individuals were
      randomly allocated either to receive ongoing botulinum injections at home by the
      nurse practitioner or to continue attending the hospital outpatient clinic and be
      injected by medical staff. MAIN OUTCOME MEASURES: The following measures were
      recorded at each visit: demographic descriptors, dosage of botulinum toxin,
      treatment interval, side-effect profile, external referrals, and a questionnaire
      to determine qualitative opinion. RESULTS: Efficacy and duration of the botulinum
      was similar in both groups. Botulinum dosage and side-effect profiles were
      similar in both groups except for significantly less dysphagia (p < .018) in the
      home group (7 vs 24 occasions). Subjective opinion by the patients indicated
      statistically significant preference for home injections. Economic analysis
      indicated that the overall cost of the treatment was less in the home injection
      group (total cost per visit $36.90 [ pound 23.36] vs $79.00 [ pound 50.01]), but
      this difference was not statistically significant. CONCLUSION: A trained outreach
      nurse practitioner provided a service that was as good as, and in certain aspects
      better than, that provided by a hospital outpatient clinic. The nurse
      practitioner provided a more flexible, much appreciated, safe, and cost-effective
      service for this client group. Wider use of outreach nurse practitioners for
      dystonia should be encouraged.

PMID- 11295009
TI  - Interferential therapy electrode placement technique in acute low back pain: a
      preliminary investigation.
AB  - OBJECTIVE: To determine the efficacy of interferential therapy (IFT) electrode
      placement technique compared with a control treatment in subjects with acute low
      back pain (LBP). DESIGN: Single-blind, randomized, controlled trial with a 3
      month follow-up. SETTING: Outpatient physiotherapy departments in hospital and
      university settings. PATIENTS: A random sample of 60 eligible patients with back
      pain (28 men, 32 women) were recruited by general practitioners and self-referral
      for physiotherapy treatment and randomly assigned to 1 of 3 groups.
      INTERVENTIONS: (1) "IFT painful area" and The Back Book, (2) "IFT spinal nerve"
      and The Back Book, and (3) "Control," The Back Book only. Standardized IFT
      stimulation parameters were used: carrier frequency 3.85 kHz; 140 Hz constant;
      pulse duration 130 micros; 30 minutes' duration. MAIN OUTCOME MEASURES: Pain
      Rating Index, Roland-Morris Disability Questionnaire (RMDQ), and EuroQol were
      completed by subjects pretreatment, at discharge, and 3-month follow-up. RESULTS:
      All groups had significant improvements in all outcomes at follow-up. Subjects
      managed by IFT spinal nerve and The Back Book displayed both a statistically
      significant (p = .030) and clinically meaningful reduction in functional
      disability (RMDQ), compared with management via IFT painful area and The Back
      Book combined or The Back Book alone. CONCLUSIONS: The findings showed that IFT
      electrode placement technique affects LBP-specific functional disability,
      providing preliminary implications for future clinical studies.

PMID- 11295010
TI  - Gross motor function of children with down syndrome: creation of motor growth
      curves.
AB  - OBJECTIVE: To create gross motor function growth curves for children with Down
      syndrome (DS) and to estimate the probability that motor functions are achieved
      by different ages. DESIGN: Nonlinear growth curve analysis by using a 2-parameter
      (rate, upper limit) model. SETTING: Early intervention programs, schools, and
      children's homes. PARTICIPANTS: One hundred twenty-one children with DS, ages 1
      month to 6 years. MAIN OUTCOME MEASURES: Gross Motor Function Measure (GMFM) and
      severity of motor impairment. RESULTS: The curves for children with mild (n = 51)
      and moderate/severe (n = 70) impairment were characterized by a greater increase
      in GMFM scores during infancy and smaller increases as the children approached
      the predicted maximum score of 85.9 or 87.9. The estimated probability that a
      child would roll by 6 months was 51%; sit by 12 months, 78%; crawl by 18 months,
      34%; walk by 24 months, 40%; and run, walk up stairs, and jump by 5 years, 45% to
      52%. CONCLUSIONS: Children with DS require more time to learn movements as
      movement complexity increases. Impairment severity affected the rate but not the
      upper limit of motor function. The results have implications for counseling
      parents, making decisions about motor interventions, and anticipating the time
      frame for achievement of motor functions.

PMID- 11295011
TI  - Chronic pain associated with spinal cord injuries: a community survey.
AB  - OBJECTIVE: To investigate, in a community sample of people with spinal cord
      injuries (SCIs), chronic pain prevalence, associated factors, sites,
      characteristics, interference with daily functioning, treatments received, and
      treatment helpfulness. DESIGN: Postal survey. SETTING: Community. PARTICIPANTS:
      Three hundred eighty-four individuals aged over 17 years with SCIs. MAIN OUTCOME
      MEASURES: Chronic Pain Grade questionnaire, Short-Form McGill Pain Questionnaire,
      pain sites, and treatments. RESULTS: Current pain was reported by 79% of
      respondents and was significantly more common in less highly educated persons,
      and individuals not employed or in school. Most common locations of current pain
      were the back (61%), hips and buttocks (61%), and legs and feet (58%). Upper
      extremity pain was experienced by 76% after the injury and by 69% currently.
      Individuals with tetraplegia were significantly more likely to have neck and
      shoulder pain than were those with paraplegia. On average, respondents reported a
      high level of pain intensity and a moderate level of pain interference with
      activities, and rated treatments received for pain as being only somewhat
      helpful. CONCLUSION: Most individuals with SCI experience chronic pain that is
      refractory to medical treatment. Further research is needed to delineate the
      causes of, and optimal treatments for, the various pain problems in this
      population.

PMID- 11295012
TI  - The effects of physical therapy in Parkinson's disease: a research synthesis.
AB  - OBJECTIVE: To present a critical review and meta-analysis of studies evaluating
      the effects of physical therapy in patients suffering from Parkinson's disease
      (PD), in terms of neurologic signs, activities of daily living (ADLs), and
      walking ability. DATA SOURCES: Articles published from 1966 to May 1999 were
      compiled by means of MEDLINE, Cochrane register of controlled trials, and CINAHL
      using combinations of the key words Parkinson's disease, exercise, exercise
      therapy, physical therapy, and group training. References presented in relevant
      publications were also examined. Articles written in English, German, or Dutch
      were included. STUDY SELECTION: Studies had to meet the following selection
      criteria: (1) patients with PD were included in the intervention study, (2) the
      effects of physical therapy (PT) were evaluated, (3) the study could be
      classified as true or quasi-experiment, and (4) the study was published in a
      journal or book. DATA EXTRACTION: Two reviewers assessed independently the
      methodologic quality of the data of each included study. One reviewer extracted
      relevant meta-analysis data. DATA SYNTHESIS: For each outcome measure the
      estimated effect size and the summary effect size (SES) were calculated, using
      fixed (ie, Hedges's g) and random effects models. The meta-analysis resulted in a
      significant homogeneous SES with regard to ADLs (.40; confidence interval [CI] =
      .17-.64) and stride length (.46; CI = .12-.82). The SES with regard to walking
      speed showed a significant heterogeneous SES, which remained significant after
      applying a random effects model (.49; CI = .21-.77). The SES with regard to
      neurologic signs was not significant (.22; CI = -.08 to .52). The small number of
      studies included and the shortcomings of the methodologic quality of these
      studies, however, bias the results of the present study. CONCLUSIONS: The results
      of the present research synthesis support the hypothesis that Parkinson patients
      benefit from PT added to their standard medication.

PMID- 11295013
TI  - Monocular patching may worsen sensory-attentional neglect: a case report.
AB  - To determine whether monocular patching influences the performance of a patient
      with primarily sensory-attentional bias on the line bisection task, we present a
      case study of a 49-year-old woman who had right cortical infarction affecting
      temporal, parietal, and occipital regions. She had primarily sensory-attentional
      bias when performing the line bisection task on a video apparatus. In hospital,
      she was tested with monocular eye patching of the left or the right eye or
      unpatched. Paradoxically, the right-eye patching significantly worsened and the
      left patch significantly improved performance. The eye may have some input to the
      ipsilateral as well as the contralateral superior colliculus. Alternatively, the
      patch-a novel tactile stimulus-may induce orienting to its side via noncollicular
      mechanisms. When using a monocular patch for any reason, clinicians should be
      aware that increased spatial bias may occur.

PMID- 11295014
TI  - Magnetic resonance imaging findings in piriformis syndrome: a case report.
AB  - Piriformis syndrome (PS) is an unusual cause of sciatica that, because of the
      lack of strict diagnostic criteria, remains a controversial clinical entity. The
      diagnosis of PS is still primarily clinical because no diagnostic tests have
      proven to be definitive. We report the case of a 30-year-old woman, affected by a
      severe scoliosis, who developed a persistent buttock pain resembling that of PS.
      The clinical suspicion was confirmed by magnetic resonance imaging (MRI) of the
      pelvis, which showed an enlargement of the left piriformis muscle with an
      anterior isplacement of the sciatic nerve. The role of MRI in the diagnosis,
      clinical definition, and therapeutic approach to PS is discussed.

PMID- 11295015
TI  - The crossed femoral nerve stretch test to improve diagnostic sensitivity for the
      high lumbar radiculopathy: 2 case reports.
AB  - The femoral nerve stretch test (FNST) is commonly used to assess high lumbar
      radiculopathy. It may be falsely positive secondary to tight or injured muscles
      of the anterior thigh, and to osseous or joint pathology in and about the hip. We
      report on the crossed FNST, which may improve the specificity of the FNST. Two
      cases that occurred within 2 months are presented. The physical examinations
      suggested high lumbar radiculopathy, which was confirmed by both the FNST and
      crossed FNST. The crossed FNST may thus be a valuable screening test that further
      supports a diagnosis of upper lumbar radiculopathy. Further study is necessary to
      identify its prevalence in the assessment of the high lumbar radiculopathy.

PMID- 11295016
TI  - Constraint-induced motor relearning after stroke: a naturalistic case report.
AB  - Constraint-induced movement therapy (CIMT) is a promising approach to promoting
      recovery of functional arm movement after stroke. However, controlled studies
      have been limited to persons who sustained strokes at least 1 year before
      beginning the treatment protocol. This case study documents the neurologic
      history and motor recovery of a woman whose natural circumstances lend support to
      the principles of CIMT. The patient sustained a right midpontine vascular infarct
      and fell simultaneously, fracturing her right humerus. Orthopedic intervention
      for the fracture mirrored the protocol suggested by proponents of CIMT by
      immobilizing her right arm. Her significant recovery of left arm use over a 1
      year period was more extensive than what would be typically expected after the
      type of cerebral infarct she incurred. Her case provides the first evidence in
      the literature that supports the principles of CIMT when it is applied
      immediately poststroke.

PMID- 11295017
TI  - The relationship between pressure ulcer incidence and buttock-seat cushion
      interface pressure in at-risk elderly wheelchair users.
AB  - OBJECTIVE: To investigate the relation between pressure ulcer incidence and
      buttock-wheelchair seat cushion interface pressure measurements. DESIGN:
      Secondary analysis of data from a randomized clinical trial. SETTING: Skilled
      nursing facility. PATIENTS: Thirty-two elderly patients (age, > or = 65 yr), with
      Braden score < or = 18 and Braden mobility and activity subscale score < or = 5,
      who used wheelchairs > or = 6 hr/d, were free of existing sitting-induced
      pressure ulcers, and weighed < or = 250 lb. INTERVENTIONS: Generic foam seat
      cushion or pressure-reducing seat cushion. MAIN OUTCOME MEASURES: The incidence
      of sitting-induced pressure ulcers over a 1- to 12-month period was compared with
      pressure measured between patients' buttocks and wheelchair seat cushions. A
      flexible pad with a 15 x 15 pressure sensor array was used to measure interface
      pressure. RESULTS: Interface pressure measured on wheelchair seat cushions was
      higher (p < or = .01 for both peak pressure and average of highest 4 pressures)
      for patients who developed sitting-acquired pressure ulcers compared with those
      patients who did not. CONCLUSIONS: Results indicated that higher interface
      pressure measurements are associated with a higher incidence of sitting-acquired
      pressure ulcers for high-risk elderly people who use wheelchairs.

PMID- 11295018
TI  - Evaluation of wheelchair seating system crashworthiness: "drop hook"-type seat
      attachment hardware.
AB  - OBJECTIVE: To evaluate the crashworthiness of commercially available hardware
      that attaches seat surfaces to the wheelchair frame. DESIGN: A low cost static
      crashworthiness test procedure that simulates a frontal impact motor vehicle
      crash. SETTING: Safety testing laboratory. SPECIMENS: Eleven unique sets of drop
      hook hardware made of carbon steel (4), stainless steel (4), and aluminum (3).
      INTERVENTIONS: Replicated seat-loading conditions associated with a 20g/48 kph
      frontal impact. Test criterion for seat loading was 16,680 N (3750 lb). MAIN
      OUTCOME MEASURES: Failure load and deflection of seat surface. RESULTS: None of
      the hardware sets tested met the crashworthiness test criterion. All failed at
      less than 50% of the load that seating hardware could be exposed to in a 20g/48
      kph frontal impact. The primary failure mode was excessive deformation, leading
      to an unstable seat support surface. CONCLUSIONS: Results suggest that
      commercially available seating drop hooks may be unable to withstand loading
      associated with a frontal crash and may not be the best option for use with
      transport wheelchairs.

PMID- 11295019
TI  - A do-it-yourself membrane-activated auditory feedback device for weight bearing
      and gait training: a case report.
AB  - An augmented auditory feedback device comprised of a thin membrane switch mini
      buzzer, and battery is described as a modification of a previously described
      feedback device. The membrane switch can be customized for the patient and is
      designed to fit inside a patient's shoe without altering the heel height. Its
      appeal lies in its simplicity of construction, low cost, and ease of
      implementation during a patient's training for weight bearing and gait. An ever
      present source of information, it provides performance-relevant cues to both
      patient and clinician about the occurrence, duration, and location of a force
      component of motor performance. The report includes suggested applications of the
      device, instructions to construct it, and a case report in which the device was
      used to improve weight bearing and gait in a cognitively healthy person with
      spina bifida.

PMID- 11295020
TI  - Disability, chronic illness, and risk selection.
AB  - As high-cost users of health care, people with disabilities or chronic conditions
      are particularly vulnerable to risk selection. Preferred risk selection, in which
      insurers avoid enrolling high-risk people, threatens their access to coverage.
      Adverse selection, in which high-risk people enroll in the most generous plans,
      compromises the financial viability of plans that are most responsive to their
      specific needs. The Americans with Disabilities Act prohibits some forms of risk
      selection, but does not prevent all disability-based distinctions in insurance
      practices. From a disability perspective, risk selection must be addressed in a
      manner that: (1) adequately reflects the health care costs of such individuals;
      (2) eliminates their need to engage in adverse selection; (3) does not stigmatize
      them; (4) preserves confidentiality of information; (5) uses substantial outcome
      measures to ensure quality; and (6) creates market conditions that discourage
      disability-based discrimination. A risk adjuster based on prior use/expenditures
      or on a diagnostic indicator sensitive to disability issues may be effective.
      Failure of reform to address risk selection may threaten the viability of a
      market-based health care system.

PMID- 11295021
TI  - The story of function-related groups--please, first do no harm.
AB  - In November 2000, the Health Care Financing Administration (HCFA) published a
      proposed rule announcing their intention to implement a prospective payment
      system for rehabilitation inpatient facilities and hospital units. In this
      system, payments are to be scaled to patient complexity through a classification
      system referred to as case-mix groups (CMGs) modeled after the Functional
      Independence Measure-Function Related Groups, which were developed from the FIM
      instrument. Under the HCFA proposal, CMGs will be derived from the Minimum Data
      Set for Post-Acute Care (MDS-PAC). This shift to the MDS-PAC, with little
      scientific evidence to support it, can have a negative impact on how the system
      expresses patient need, on how patients access services, and on the equity of
      hospital payments.

PMID- 11295022
TI  - The evolution of Medicare financing policy for graduate medical education and
      implications for PM&R: a commentary.
AB  - Currently, the only explicit payers for graduate medical education (GME) in the
      United States are the federal and state governments. Of these, Medicare is by far
      the largest and most predictable payer. Through the prospective payment system,
      Medicare reimburses teaching institutions for both their direct and indirect
      costs associated with their GME programs. Because a well-educated workforce
      benefits patients covered by private, as well as public insurance, various
      proposals have been advanced to establish an all-payer pool to distribute the
      financial burden more equitably. Furthermore, Medicare policy affects physician
      supply. There is increasing recognition of potential physician oversupply,
      raising policy questions about the government's longstanding support of GME. In
      comparison with other specialties, physical medical and rehabilitation (PM&R) may
      receive more favorable treatment under future GME funding plans, for 2 reasons.
      First, under the formulas used by Medicare, PM&R training slots typically bring
      in more indirect revenue to teaching hospitals than is consumed in indirect
      expenses. This makes PM&R a relatively more attractive program to retain in the
      face of mandated reductions in training slots. Second, in many parts of the
      country, PM&R is not threatened by oversupply, making cuts less likely.
      Nevertheless, the high percentage of non-US medical graduates entering PM&R
      training may make the specialty vulnerable to future reductions in funded
      training slots.

PMID- 11295023
TI  - Strengthening of the proximal muscles in Charcot-Marie-Tooth disease.

PMID- 11295024
TI  - Serum albumin--a marker of fluid overload in dialysis patients?

PMID- 11295025
TI  - Growth factors in the treatment of wasting in kidney failure.
AB  - Protein-energy malnutrition is relatively common in patients with advanced renal
      failure and is associated with an increase in morbidity and mortality.
      Accordingly, there is a need to develop more effective treatments to enhance the
      nutritional status of these patients. One such approach is the use of recombinant
      growth factors and anabolic steroids for malnourished patients refractory to
      standard nutritional therapy. In this article, we review the current state of our
      knowledge regarding the potential use of these agents in malnourished renal
      failure patients and conclude that although the studies performed to date are
      indeed encouraging, further and more extensive clinical trials are required to
      firmly establish their efficacy and safety profile and the indications for
      clinical use.

PMID- 11295027
TI  - Use of isomalto-oligosaccharide in the treatment of lipid profiles and
      constipation in hemodialysis patients.
AB  - Chronic constipation and hyperlipidemia, one of the many atherogenic risk
      factors, were common complications in hemodialysis (HD) patients. The present
      trial evaluates the therapeutic efficacy of isomaltose-oligosaccharide (IMO) in
      the treatment of chronic severe constipation and its effect on lipid profiles in
      20 HD patients. After a 2-week basal period, these patients were allocated to
      receive 30 g of IMO for a 4-week period. After the study period, these patients
      were observed for another 4 weeks. Bowel frequency, gastrointestinal
      symptomatology, biochemical parameters, and lipid profiles were assessed. All
      patients completed this study. IMO induced a significant increase in number of
      bowel movements and hence improvement of constipation in 76.3% + 30.9% of
      patients during the 4-week treatment. Some, but well-tolerated gastrointestinal
      side effects were noted. Statistically significant decreases in total cholesterol
      and triglycerides (TG) and increases in high density lipoprotein-cholesterol (HDL
      C) were noted after IMO treatment (P <.05 compared with baseline and controls).
      After the study period, those patients receiving IMO had reductions in levels of
      total cholesterol -17.6%, TG -18.4%, and elevations of levels of HDL-C by +39.1%.
      In conclusion, IMO once a day is well tolerated and effective in increasing bowel
      frequency and improving constipation in HD patients. In addition, IMO treatment
      was effective in lowering total cholesterol and triglycerides and in raising HDL
      C in HD patients.

PMID- 11295026
TI  - Homocysteine lowering effect of different multivitamin preparations in patients
      with end-stage renal disease.
AB  - OBJECTIVE: Hyperhomocysteinemia occurs in nearly 100% of patients with end-stage
      renal disease (ESRD) and is associated with increased morbidity and mortality.
      Means to reduce elevated homocysteine concentrations is supplementation with
      folic acid, vitamin B6, and vitamin B12. However, doses of vitamins required for
      optimized treatment are subject of debate. Therefore, the effect of 2 different
      multivitamin preparations on the homocysteine concentrations in patients with
      ESRD were compared. DESIGN: Patients received 3 times per week either 2 tablets
      of preparation A (800 microg folic acid, 6 microg vitamin B12, 10 mg vitamin B6),
      2 tablets of preparation B (160 microg folic acid, no vitamin B12, 10 mg vitamin
      B6), or placebo for a period of 12 weeks with control of total homocysteine
      (tHcy) levels at baseline, and at 4, 8, and 12 weeks. SETTING: The study was
      performed at the University Hospital of Magdeburg, Germany in patients with ESRD
      treated with chronic intermittent maintenance hemodialysis. RESULTS: Preparation
      A reduced the tHcy concentration significantly by nearly 50%, whereas preparation
      B did not change the tHcy concentration in comparison with placebo. However, tHcy
      was not normalized in the majority of patients receiving preparation A.
      CONCLUSION: The reduction of tHcy achieved by a multivitamin containing 800
      microg folic acid was substantial and even higher than the reduction reported in
      supplementation studies using higher doses of folic acid alone. Nevertheless,
      hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin
      supplementation, in contrast with results obtained in healthy volunteers.

PMID- 11295028
TI  - Identification of the factors associated with compliance to therapeutic diets in
      older adults with end stage renal disease.
AB  - OBJECTIVE: To identify theory based factors pertinent to compliance with
      therapeutic diets. DESIGN: A paper and pencil survey was read to volunteer
      hemodialysis patients in outpatient dialysis clinics. SUBJECTS: A convenience
      sample of 276 hemodialysis patients aged 50 years and older who agreed to be
      interviewed during treatment. STATISTICAL ANALYSIS: Descriptive statistics were
      used to report responses to all survey questions. The Fisher exact test was used
      to test associations between the dependent variable, dietary compliance, and
      independent variables, which included knowledge, perceived severity of illness,
      attitudes toward compliance, environmental factors, perceived barriers, self
      efficacy, and perceived health benefits. Principal Components Analysis determined
      final scale items. Logistic regression was used to develop a model of independent
      variables profiling the compliant patient. RESULTS: Subjects were more likely to
      be compliant if they indicated favorable attitudes toward compliance (P =.0076),
      a supportive environment (P =.0107), and knowledge about their diet (P =.0014). A
      logistic regression model of compliance indicated that subjects who followed
      their special diets were more likely to have higher knowledge (odds ratio [OR] =
      1.092, 95% CI = 1.006, 1.186), perceived fewer barriers (OR = 1.094, 95% CI =
      0.841, 1.226), being white race (OR = 0.710, 95% CI = 0.399, 1.263), and having
      gout (OR = 9.349, 95% CI = 1.139, 76.714). APPLICATION: Health professionals
      should apply these findings in providing dietary education focused on improving
      not just knowledge, but attitudes and family support. Nutrition education and
      health promotion applications geared to non-white populations could be
      particularly important as tools to improve dietary compliance.

PMID- 11295029
TI  - Demineralization of a wide variety of foods for the renal patient.
AB  - OBJECTIVE: To develop the (1) simplest, most efficacious, mineral (phosphorous,
      potassium, and sodium) reduction procedures applicable to a total dietary
      selection of foods that will (2) preserve postprocessing food taste and texture
      expectations. DESIGN: Preprocessing and postprocessing mineral analysis of more
      than 245 individual samples. SETTING: Analysis of mineral content performed at
      certified food laboratory in Omaha, NE. PARTICIPANTS: Renal and control
      volunteers participated as postprocessing test consumers. INTERVENTION: Food
      materials were subjected to aqueous mineral extraction involving variations in
      (1) pretreatment handling, (2) aqueous temperatures, and time depending on cell
      type and initial state (raw, canned, dried). Measurements of remaining mineral
      concentrations of phosphorous, potassium, and sodium were performed on samples
      drawn at various time points. MAIN OUTCOME MEASURE: Determination of remaining
      postprocessing concentrations of target minerals and calculation of the maximum
      mineral reduction achieved with each food type. RESULTS: The phosphorous
      reduction range for vegetables, legumes, meats, flours, and cheddar cheese was
      51% +/- 33%, 48% +/- 25%, 38.5% +/- 22.5%, 70.5% +/- 13.5%, and 19%,
      respectively; for potassium, the reduction range for vegetables, legumes, meats,
      flours, cheddar cheese, and fruit was 59% +/- 40%, 78.5% +/- 20.5%, 57% +/- 41%,
      94% +/- 3%, 99%, and 43% +/- 16%, respectively; for sodium, the reduction range
      for vegetables, meats, and cheddar cheese was 83.5% +/- 14.5%, 67.5% +/- 27.5%,
      and 97%, respectively. CONCLUSION: Consuming a total dietary selection of
      demineralized foods is expected to have a significant positive impact on the
      renal patient's problematic hematologic mineral values and nutritional profile.
      Reducing food mineral load will make restricted foods permissible once again.

PMID- 11295030
TI  - Effects of calorie and fluid intake on adverse events during hemodialysis.
AB  - PURPOSE: To investigate the incidence of adverse events during hemodialysis
      treatments as a function of calories and fluid intake. METHODS: The study period
      was August 3-26, 1999. Hemodialysis visits were studied. Twenty-three patients
      receiving hemodialysis during the 2nd shift on Tuesday, Thursday, and Saturday
      were studied. A total of 166 hemodialysis patient visits were studied. Data
      collected included: amount of fluid and food consumed, blood pressure levels, and
      mannitol use during each hemodialysis treatment; and any symptoms that occurred
      either during or after the dialysis treatment (hypotension, nausea, vomiting,
      diarrhea, cramping, and access problems). RESULTS: Using regression analysis,
      calories and fluids were strong predictors of both hypotension (P =.003) and
      mannitol use (P =.000), but not of cramping or access problems. Patients were 3
      times more likely to have hypotension if taking any fluids (P =.011). Patients
      consuming >200 calories were 2 times as likely to have hypotension (P =.058).
      Patients were 5 times more likely to use mannitol if taking any fluids (P =.005).
      Mannitol use increased significantly (P =.001) with those patients consuming >200
      calories. CONCLUSION: Patients who ate more than 200 calories and consumed more
      than 200 mL of fluid during hemodialysis had an increased incident of hypotensive
      events and increased use of mannitol.

PMID- 11295031
TI  - The role of the dietitian in a multicenter clinical trial of dialysis therapy:
      the Hemodialysis (HEMO) Study.
AB  - The Hemodialysis (HEMO) Study is a randomized multicenter prospective clinical
      trial, supported by the National Institute of Diabetes, Digestive, and Kidney
      Diseases of the National Institutes of Health. The trial is designed to assess
      the effects of a standard versus higher dialysis dose and low versus high
      dialysis membrane flux on morbidity and mortality of chronic hemodialysis
      patients. The role of the dietitian in the HEMO Study is to support and maintain
      the nutritional status of randomized participants. To ensure participant safety,
      nutritional status is closely monitored by a variety of biochemical and
      participant-reported parameters. Serum albumin and equilibrated normalized
      protein catabolic rates are obtained monthly. Appetite assessment and dietary
      energy and protein intakes using a 2-day diet diary assisted recall are
      ascertained at baseline and on a yearly basis. Consumption of vitamins, minerals,
      and nutritional supplements, including oral enterals, tube feedings, and
      parenteral nutrition, is obtained at least once a year. In addition,
      anthropometry is performed at baseline and on a yearly basis. Prespecified
      changes in serum albumin level or body weight trigger action by the dietitian to
      prevent protein calorie malnutrition. The HEMO Study dietitians play a vital role
      in carrying out the nutrition program for the trial. The HEMO Study should
      provide important information about the natural history of the nutritional status
      of chronic hemodialysis patients and the impact of dialysis dose and dialysis
      membrane flux on these parameters.

PMID- 11295032
TI  - Patient education. Renal nutrition: Hawaiian style.

PMID- 11295034
TI  - Expression analysis and chromosome location of a novel gene (H11) associated with
      the growth of human melanoma cells.
AB  - We have previously described the isolation of a new human gene, H11, that codes
      for a 25 kDa phosphoprotein with autokinase activity the expression of which is
      required for cell growth. The data described in this report extend these
      findings. Using FISH and M-FISH we show that H11 which maps at chromosome site
      12q24.1-12q24.31 is not involved in chromosomal translocations. The tissue
      distribution of H11 mRNA is restricted, with expression being most abundant in
      skeletal muscle, heart, prostate and placenta. The H11 protein is cytoplasmic and
      it is associated with the plasma membrane. Cell surface localization in
      particulate aggregate formations suggests that it may be complexed to proteins
      involved in the transfer of extracellular growth signals.

PMID- 11295035
TI  - Role of laminin in ovarian cancer tumor growth and metastasis via regulation of
      Mdm2 and Bcl-2 expression.
AB  - Ovarian cancer is among the most lethal cancers in women because of its high
      metastatic potential and lack of response to therapy. An experimental model to
      study this disease was developed using a transformed granulosa cell line
      expressing a mutant p53 and Ha-ras. When injected into the ovary of nude mice in
      the presence of laminin-1, tumors develop in the ovary and peritoneum and
      metastasize to various organs, leading to death within 21 days. In contrast, when
      cells were injected in the presence of gelatin, development of tumors was slower
      and no metastases were observed by day 21. Here we investigated the possible
      mechanism by which laminin-1 exerts its promotion of tumorigenesis and
      metastasis. Cells were co-injected with laminin-1 and active laminin peptides
      from the alpha1; (A13: RQVFQVAYIIIKA, A12: WVTVTLDL RQVFQ, AG73: LQVQLSIR, IKVAV)
      and beta1 (YIGSR) chains. Ovarian tumor growth and metastasis were increased in
      the presence of laminin-1 plus either AG73 peptide, IKVAV, or A13, and were
      significantly reduced in the presence of A12 or YIGSR. Expression of Bcl-2 and
      Mdm2 was higher by 3.5- and about 100-fold, respectively, in ovarian tumors grown
      in the presence of laminin compared to tumors grown in the presence of gelatin.
      Moreover, peptides A13 and AG73 further elevated Bcl-2 expression by 6- and 7
      fold respectively, while IKVAV yielded expression similar to laminin-1. YIGSR and
      A12 reduced the expression of Bcl-2 by 7- and 3-fold, respectively, compared to
      treatment with laminin-1. A13 and AG73 increased Mdm2 expression by 1.8- and 1.3
      fold, respectively, while IKVAV, A12, and YIGSR were without effect. Thus,
      laminin-1 exerts its proliferative effect on the development of ovarian tumors
      via upregulation of survival genes such as Bcl-2 and Mdm2. Peptides A13 and AG73
      (which increased tumor growth and spread) enhance the expression of these genes
      and A12 and YIGSR (which decrease tumor growth and spread) attenuate their
      expression. IKVAV probably enhances tumor growth and metastasis by another
      mechanism.

PMID- 11295036
TI  - Comparative genomic hybridization and cytogenetic analysis in a bronchial
      adenoma: three clones with different chromosomal aberrations.
AB  - Classical chromosomal analysis and comparative genomic hybridization (CGH) were
      performed in a tubular bronchial gland adenoma. Trisomy of chromosomes 2, 11, 18
      and 20 and clonal loss of Y were found in cultured cells derived from two
      different kryotubes; this was also confirmed by CGH from one of these tubes.
      Cells from two other tubes, investigated by CGH only, showed gains and losses of
      parts of chromosome 11q in one, and in the second additional gain of the distal
      portion of 9q and 17q, respectively. CGH analysis of tumor DNA extracted from
      paraffin-embedded sections showed no chromosomal imbalances. In cell culture
      growth the advantage of specific clones probably altered the clone distribution.
      This study highlights the risk of cytogenetic analysis based on cell cultures
      only.

PMID- 11295037
TI  - Indomethacin and telomerase activity in tumor growth retardation.
AB  - It is well-recognized that cycloogygenase inhibitors attenuate tumor growth in
      tumor models, although underlying mechanisms are unclear. In the present study we
      report that indomethacin retards MCG-101 tumor growth on mice by induction of
      apoptosis/necrosis and inhibits telomere elongation. The inhibition of telomerase
      activity by NSAIDs (indomethacin, mobic, sulindac sulfone, suramin) was, however,
      not a universal finding, since a mouse melanoma (K1735-M2) did not respond. By
      contrast, a human cell line of colon carcinoma origin (HT-29), responded by both
      retarded growth and telomerase activity despite a low intrinsic production of
      prostaglandins, mainly PGE2. Therefore, it is not likely that indomethacin
      inhibition of tumor growth and telomere elongation is directly related to Cox
      1/Cox-2 activities in tumor cells. Also, NSAIDs at 25 microM (sulindac sulfone)
      decreased growth and telomerase activity in MCG-101 cells, without any effects on
      PGE2 production, while ibuprofen reduced PGE2 production but had no effect on
      growth or telomerase activity. Our results demonstrate that cyclooxygenase
      inhibitors can retard tumor growth both in murine tumors and in human tumor cells
      by inhibition of telomerase activity in addition to previously recognized
      mechanisms as induction of apoptosis, inhibition of cell proliferation, influence
      on the expression of growth factors around growing tumors and attenuation of
      neoangiogenesis.

PMID- 11295038
TI  - Identification of a novel beta-chemokine, MEC, down-regulated in primary breast
      tumors.
AB  - Chemokines represent a family of low molecular weight secreted proteins that
      primarily function in the activation and migration of leukocytes. A number of
      additional functions of chemokines have also been identified including growth of
      tumor cells, angiogenesis and development. An iterative search for new chemokines
      has identified a cDNA that encodes a new member of the CC(beta) chemokine family.
      The gene has been named MEC, for mammary enriched chemokine. MEC expression was
      found at high levels in many mammary gland samples and was also detected at lower
      levels in several other epithelial-enriched tissues, such as salivary gland,
      colon, and prostate. Northern blot analysis demonstrates that MEC expression was
      highly reduced or eliminated in a majority of human breast tumors as compared to
      normal adjacent tissue. In situ hybridization demonstrates that MEC was
      abundantly expressed in normal mammary ductal epithelium, but expression was
      absent or reduced in various mammary tumor types of epithelial origin. These
      observations suggest that MEC may be useful as a diagnostic tool in oncology, and
      may play a role in regulating mammary carcinogenesis. The absence of MEC may also
      contribute to the host's immune response to tumors.

PMID- 11295039
TI  - Antitumor effects of Newcastle Disease Virus in vivo: local versus systemic
      effects.
AB  - Newcastle Disease Virus (NDV) has interesting anti-neoplastic and pleiotropic
      immune stimulatory properties. The virus preferentially replicates in and kills
      tumor cells and appears to be safe and to varying degrees effective in phase II
      clinical studies in the US and in Europe. Here we have compared various lytic and
      non-lytic strains of NDV with regard to their antitumor effects after local or
      systemic application. As tumor models we used human metastatic melanoma
      xenotransplants in nude mice and murine metastatic colon carcinoma (CT26), renal
      carcinoma (Renca) and lymphoma (ESb) cell lines. Intra or peri-tumoral
      application of NDV or NDV infected tumor cells showed more pronounced antitumor
      activity than systemic application even when in the latter case much higher dose
      ranges were used. In the CT26 colon carcinoma model the non-lytic strain Ulster
      showed stronger antitumor activity than the lytic strain 73T. In the human MeWo
      melanoma xentransplant model strong antitumor bystander effects were observed by
      20% admixture of melanoma cells pre-infected in vitro with NDV (either strain
      Ulster or Italien). Virus therapy of pre-established human melanomas by intra
      tumoral injection of NDV was effective with the lytic strain Italien but not with
      the non-lytic strain Ulster. Systemic anti-metastatic effects were never observed
      with NDV alone in contrast to previous results obtained with NDV modified tumor
      vaccines.

PMID- 11295040
TI  - Underexpression of cyclin-dependent kinase inhibitor p27 is associated with poor
      prognosis in serous ovarian carcinomas.
AB  - Reduced expression of a cyclin-dependent kinase inhibitor, p27, has been reported
      to be associated with poor prognosis in several human cancers. The aim of this
      study was to investigate the potential role of p27 in ovarian cancer development
      and progression. Immunohistochemical expression of p27 was determined using 117
      epithelial ovarian tumor tissues and 8 normal ovaries. p27 mRNA expression was
      examined by semi-quantitative PCR amplification using 26 ovarian cancer samples.
      Nuclear staining of p27 was commonly observed in the normal ovarian surface
      epithelium and the epithelial cells of germinal inclusion cysts. Positive p27
      staining rates were significantly higher in serous adenomas (p=0.006) and in
      serous LMP tumors (p=0.013) than that in serous carcinomas (Fisher's exact test).
      In serous ovarian cancers, positive p27 staining rate was significantly higher in
      early stage (stage1/2) than that in advanced stage (stage 3/4) diseases (p=0.030,
      Fisher's exact test). Log-rank testing showed that negative p27 expression
      significantly correlates with poor survival in serous ovarian cancer patients
      (p=0.041). Considerable levels of p27 mRNA were detected in all ovarian cancer
      samples examined. These results suggest that the underexpression of p27 caused by
      post-translational mechanism may contribute to the development and progression
      and result in poor prognosis of serous ovarian cancers.

PMID- 11295041
TI  - Expression profiles of betaTRCP1 and betaTRCP2, and mutation analysis of
      betaTRCP2 in gastric cancer.
AB  - betaTRCP1 and betaTRCP2, components of the beta-catenin-ubiquitin ligase complex,
      are negative regulators of the WNT signaling pathway. We have previously isolated
      the betaTRCP2 gene, and detected betaTRCP2 in all gastric cancer cell lines
      examined. Here, expression profiles of betaTRCP1 and betaTRCP2 in various normal
      tissues and in primary gastric cancer were investigated. betaTRCP1 was
      predominant in small intestine, while betaTRCP2 was predominant in stomach.
      betaTRCP1 was expressed in gastric cancer cell lines MKN28, MKN45, MKN74, and
      KATO-III, but not in any cases of primary gastric cancer. betaTRCP2 was expressed
      in most cases of primary gastric cancer at almost the equal level in tumor and in
      non-cancerous portion of gastric mucosa. As betaTRCP2 was found to be the major
      betaTRCP expressed in gastric cancer, genetic alterations of betaTRCP2 in 7
      gastric cancer cell lines and 12 cases of primary gastric cancer were
      investigated. A nucleotide substitution (Tright curved arrow C) at the nucleotide
      position 1486 of betaTRCP2 was identified in OKAJIMA cells, which lead to F462S
      amino acid substitution in the seventh WD-repeat domain. F462 was conserved among
      betaTRCPs derived from human, mouse, Xenopus laevis, and Drosophila melanogaster.
      As WD-repeats of betaTRCPs are the substrate-recognition motif of the beta
      catenin-ubiquitin ligase, F462S amino-acid substitution might lead to beta
      catenin stabilization, and might be implicated in carcinogenesis through
      activation of the WNT signaling pathway. This is the first report on
      comprehensive expression analyses of betaTRCP1 and betaTRCP2, and also on
      mutation analysis of betaTRCP2.

PMID- 11295042
TI  - The immune system, apoptosis and apoptosis-related proteins in human ovarian
      tumors (a review).
AB  - Our studies on the relationships among the lymphoid system, apoptosis and
      apoptosis-related proteins (ARP) in human ovarian benign cysts, borderline
      tumors, and carcinomas are reviewed and analyzed. Fas and Fas ligand are
      expressed in 50% to 80% of the epithelial cells in all studied tumors. Many bcl-2
      positive tumor epithelial cells are seen in benign cysts and they disappear as
      tumorigenesis progresses, whereas p53 protein is found only in borderline tumors
      and in carcinomas. Many exceptions to the opinion that bcl-2 inhibits apoptosis
      and p53 promotes it are encountered. Bcl-2 is lacking in epithelial cells of
      mucoid tumors of all grades, and its absence does not stimulate their apoptosis.
      P53 protein is absent from most lymphocytes, macrophages and epithelial tumor
      cells, nevertheless, they undergo apoptosis. Indeed, in many tumors apoptosis is
      regulated without the participation of bcl-2 and p53. Different components of the
      immune system become active during different stages of tumor development. The
      weak reaction of T-cell killers and macrophages is typical in benign cysts. In
      borderline tumors, the activity of T-cell killers increases in the parenchyma,
      and that of T helpers and macrophages in the stroma. In carcinomas with high
      lymphoid infiltration, a strong reaction of macrophages and T cell killers in the
      tumoral parenchyma as well high reaction of T helpers and B lymphocytes in the
      stroma are typical. Apoptosis that should protect against tumor also stimulates
      apoptotic death of lymphocytes and macrophages, and this has catastrophic
      consequences, as seen in weakly infiltrated carcinomas. In conclusion, our
      studies indicate that during malignancy the major task of the immune system is
      curtailment and control of tumorigenesis.

PMID- 11295043
TI  - Effect of initial tumor stage on patient follow-up after potentially curative
      surgery for cutaneous melanoma.
AB  - The optimal follow-up strategy after completion of therapy for melanoma is not
      known. We evaluated the effect of TNM stage on the self-reported surveillance
      strategies employed by practicing plastic surgeons caring for otherwise healthy
      patients subjected to potentially curative treatment for cutaneous melanoma.
      Hypothetical patient profiles and a detailed questionnaire based on these
      profiles were mailed to a random sample (N=3,032) of the 4,320 members of the
      American Society of Plastic and Reconstructive Surgeons. The effect of TNM stage
      on the surveillance strategies chosen was analyzed by repeated-measures ANOVA.
      There were 1,142 responses to the 3,032 surveys; 395 were evaluable. Plastic
      surgeons often do not provide postoperative follow-up themselves; this was the
      most frequent reason for non-evaluability. Surveillance of patients after
      resection of melanoma relies most heavily on office visits, chest X-ray, CBC, and
      liver function tests. All other surveillance modalities are used infrequently.
      Most respondents modify their surveillance practices slightly according to the
      patient's initial TNM stage. Most commonly used modalities are employed
      significantly more frequently with increasing TNM stage. This effect persists
      through ten years of follow-up, but the differences across stages are tiny. We
      conclude that most plastic surgeons performing surveillance after potentially
      curative surgery in otherwise healthy patients with melanoma use similar follow
      up strategies for patients of all TNM stages. These data permit the rational
      design of a controlled clinical trial of high-intensity vs. low-intensity follow
      up.

PMID- 11295044
TI  - Apoptotic activity of novel bile acid derivatives in human leukemic T cells
      through the activation of caspases.
AB  - The therapeutic efficacies of bile acids, such as ursodeoxycholic acid (UDCA) and
      chenodeoxycholic acid (CDCA), have been widely demonstrated in various liver
      diseases, suggesting that they might protect hepatocytes against common
      mechanisms of liver damage. Although they have been shown to prevent apoptotic
      cell death in certain cell lines, we have previously reported that a novel
      derivative (HS-1030) of UDCA significantly inhibited cell growth and induced
      apoptosis in cancer cells. To develop more effective agents, we synthesized
      several derivatives, named HS-1183, HS-1199 and HS-1200, based on the structure
      of UDCA and CDCA, and investigated them for anti-proliferative activity in Jurkat
      cells, a human leukemic T cell line. Whereas UDCA and CDCA had no significant
      effects on the growth of Jurkat cells in the concentration range tested, both HS
      1199 and HS-1200 completely inhibited the cell proliferation, and HS-1183 showed
      only a weak inhibitory activity. Furthermore, chromatin condensation, DNA ladder
      formation and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) were
      observed after treatment of novel bile acids, indicating the occurrence of
      apoptotic cell death, which was associated with down-regulation of caspase-3 and 
      8. The apoptotic manifestations such as PARP cleavage and DNA fragmentation were
      abolished in the presence of the tripeptide caspase inhibitor zVAD-fmk or the
      specific caspase-3 inhibitor DEVD-fmk. Our data thus demonstrate that novel bile
      acid derivatives-induced apoptosis of leukemic T cells is dependent on caspase
      activation.

PMID- 11295045
TI  - SMRT as a T3SF-binding protein.
AB  - p53-binding consensus-like sequence (T3SF) is located in the murine promoter
      region of tissue inhibitor of metalloproteinase 3 gene. To identify the genes
      that encode proteins that bind to T3SF DNA sequence, we screened a cDNA library
      using the Southwestern technique. The SMRT gene was cloned as one of the
      candidates. Addition of antibody against SMRT reduced the intensity of a band
      that is supposed to contain SMRT in electrophoresis mobility shift assay,
      although antibody against p53 had no effect. Ultraviolet (UV)-irradiation reduced
      the intensity of the SMRT complex whereas p53 complex was stabilized by UV
      irradiation. These results suggest that SMRT may bind to T3SF sequence in p53
      independent manner and dissociate from the sequence by UV irradiation.

PMID- 11295046
TI  - Molecular cloning and characterization of human Frizzled-8 gene on chromosome
      10p11.2.
AB  - Mouse Frizzled-8, encoding a WNT receptor, is a potent cancer-associated gene to
      activate the beta-catenin-TCF pathway. However, these is a possibility that mouse
      Frizzled-8 might be a pseudogene, because structure and expression profile of
      mouse Frizzled-8 mRNA are still unclear. We have cloned and characterized the
      human Frizzled-8 (FZD8) gene, a human homologue of mouse Frizzled-8. Comparison
      between FZD8 genome clones and FZD8 cDNA clones isolated in this study revealed
      no intron within the FZD8 gene. FZD8 was found to encode a 694 amino-acid
      polypeptide with the frizzled-like cysteine-rich domain, seven transmembrane
      domains, and the C-terminal Ser/Thr-X-Val motif. Among human FZD family, FZD8 was
      most homologous to FZD5 (total amino-acid identity 69.1%). The 4.0-kb FZD8 mRNA
      was detected in fetal kidney and brain, and also in adult kidney, heart,
      pancreas, and skeletal muscle. These results indicate that human FZD8 is not a
      pseudogene. The FZD8 gene was mapped to human chromosome 10p11.2 by fluorescence
      in situ hybridization. Among human cancer cell lines, FZD8 was relatively highly
      expressed in HeLa S3 (cervical uterus cancer) and A549 (lung cancer). Up
      regulation of FZD8 might play key roles in several types of human cancer through
      activation of the beta-catenin-TCF pathway.

PMID- 11295047
TI  - Synergistic effects of dexamethasone and genistein on the expression of Cdk
      inhibitor p21WAF1/CIP1 in human hepatocellular and colorectal carcinoma cells.
AB  - Previous studies have shown that dexamethasone, a synthetic glucocorticoid, can
      induce a G1 arrest, however, genistein, a natural isoflavonoid phytoestrogen,
      induces a G2/M arrest in the cell cycle progression in various cancer cell lines.
      A block of cell cycle checkpoint by dexamethasone and genistein correlates with a
      selective induction of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 in a
      tumor suppressor p53-independent manner and abolishment of Cdk2 phosphorylation.
      In the present study, the effects of dexamethasone and genistein (both singly and
      combined) on the expression of p21 in human hepatocellular Hep G2 and colorectal
      Colo320 HSR carcinoma cells were evaluated. Whereas dexamethasone mildly induced
      the level of p21 protein, genistein strongly increased the expression of p21
      protein in our experimental condition. Both compounds also activated p21 promoter
      reporter constructs. The combined effects of dexamethasone and genistein on the
      induction of p21 protein and activation of p21 promoter were synergistic in both
      cell lines. These findings indicate that dexamethasone and genistein act in a
      synergistic fashion and have potential for combination chemotherapy for the
      treatment of liver and colon cancer.

PMID- 11295048
TI  - Polymorphism and allelic loss at the AS3 locus on 13q12-13 in esophageal squamous
      cell carcinoma.
AB  - Our previous studies of esophageal squamous cell carcinoma (ESC) revealed that
      frequent loss of heterozygosity (LOH) on 13q12-13 was associated with lymph node
      metastasis. These results suggest that 13q12-13 may harbor a tumor suppressor
      gene which regulates lymph node metastasis. Recently, a new tumor suppressor
      candidate, AS3, was identified in this region. We therefore examined AS3
      alterations by PCR-SSCP and RT-PCR. Although polymorphisms were found in exon 10
      and introns 21, 23, 25 and 29, a possible tumor specific mutation in exon 6 was
      identified in only one of 31 ESC-derived cell lines, indicating that the
      remaining allele of AS3 was rarely inactivated by mutational events.
      Interestingly, ESC patients with rare alleles frequently exhibited lymph node
      metastasis. These results suggest that polymorphic variation and LOH at the AS3
      locus might be associated with lymph node involvement in ESC.

PMID- 11295049
TI  - Selective growth inhibition by sangivamycin of human umbilical vein endothelial
      cells.
AB  - In the course of our screening for selective growth inhibitors of human umbilical
      vein endothelial cells (HUVECs), we isolated sangivamycin from the culture
      filtrate of Streptomyces. It inhibited the growth of HUVECs at approximately 30
      times lower concentration than that needed to inhibit the growth of WI-38 human
      fibroblasts. Structurally-related nucleosides, such as toyocamycin, tubercidin,
      and formycins A and B, did not show the differential inhibition. Although
      sangivamycin is known to inhibit protein kinase C, other protein kinase C
      inhibitors did not inhibit the growth of HUVECs selectively. Sangivamycin
      effectively inhibited S-phase induction in HUVECs, like TNP-470 and LLnL, known
      selective inhibitors. However, unlike them sangivamycin did not induce p21
      expression. On the other hand, sangivamycin was found to inhibit DNA synthesis
      selectively in HUVECs. Thus, sangivamycin was shown to be a new selective growth
      inhibitor of HUVECs acting on DNA synthesis.

PMID- 11295050
TI  - Germline mutation of the PTEN gene in a Japanese patient with Cowden's disease.
AB  - Cowden's disease (CD) is an autosomal dominant disorder which confers a high
      susceptibility to diverse benign and malignant tumors. The PTEN (phosphatase and
      tensin homologue deleted in chromosome ten) gene has been identified as a tumor
      suppressor gene responsible for cancers of the endometrium, ovary, prostate, and
      glioblastomas. Recently, germline mutations of this gene were also found in
      patients with CD, and it is now recognized as a gene responsible for this
      disease. We identified a germline nonsense mutation at codon 130 in exon 5 of
      PTEN in a 56-year-old Japanese woman with CD. The patient had adenoid facies and
      mucocutaneous lesions including multiple facial papules, acral keratoses on neck
      and shoulders, palmoplantar keratoses, multiple oral papillomas, scrotal tongue,
      mucosal and cutaneous hemangiomas, and a sclerotic fibroma on the arm. She also
      had benign and malignant polypoid neoplasms throughout the entire digestive
      tract, including adenocarcinoma of the colon and submucosal lipomas of the
      rectum, as well as bilateral breast carcinomas, multinodular goiters, an ovarian
      cyst with a fibroma-like nodule, hepatic hemangiomas, and abdominal hernia. We
      searched CD cases with the same genotypic PTEN mutation as the present case and
      compared their phenotypes. Further studies will disclose a better understanding
      of the role of mutation in the PTEN gene in the course of tumorigenesis of both
      benign and malignant tumors developed in patients with CD.

PMID- 11295051
TI  - Non-isotopic silver-stained SSCP is more sensitive than automated direct
      sequencing for the detection of PTEN mutations in a mixture of DNA extracted from
      normal and tumor cells.
AB  - The sensitivity of non-isotopic PCR-SSCP was compared to direct sequencing of
      PTEN exons. DNA from leukocytes derived from healthy donors, and from the
      glioblastoma cell line LN319 was extracted and mixed in different proportions
      from 0 to 100%. The LN319 cell line contains a point mutation at codon 15 exon 1
      of the PTEN gene. The PCR-SSCP experiments demonstrated mutations in samples
      containing as little as 10% tumor DNA. In contrast, direct DNA sequencing
      experiments were less sensitive, requiring 30-70% of tumor DNA in the sample,
      depending on the DNA strand sequenced. In conclusion, PCR-SSCP, in our hands, is
      more sensitive than automated sequencing for detecting PTEN point mutations. We
      recommend to always sequence both strands, and take into account that samples
      containing less than 30% tumor cells should not only be sequenced, but also
      studied by PCR-SSCP in order to discriminate false negative results.

PMID- 11295052
TI  - Cytoskeletal-induced alterations in the adhesion of HT-1080 fibrosarcoma cells to
      extracellular matrix.
AB  - We have investigated the adhesion of the human fibrosarcoma cell line, HT-1080,
      transfected with glial fibrillary acidic protein (GFAP) to a variety of
      extracellular matrix macromolecules (ECM) including collagen type IV, laminin,
      and fibronectin. The GFAP-transfectants demonstrated altered adhesiveness to
      extracellular matrix substrates when compared to controls. GFAP-positive, heavy
      metal-induced fibrosarcoma cells were more adherent to plastic and collagen type
      IV than were the parental or uninduced cells. In contrast, GFAP-positive
      fibrosarcoma cells were less adherent to laminin- or fibronectin-coated dishes
      than controls. Time course adhesion studies over 9 days showed that the heavy
      metal-induced fibrosarcoma cells progressively became more adherent to collagen
      type IV and less adherent to laminin- or fibronectin-coated dishes than did
      uninduced cells. However, with the removal of heavy metal from the medium, the HT
      1080 fibrosarcoma cells were restored to their original adhesive potential. By
      phase microscopy, uninduced and induced HT-1080 cells demonstrated different
      morphological features and remained viable in an anchorage-dependent fashion on
      collagen type IV as a substrate. By way of contrast, GFAP-induced HT-1080 cells
      were not particularly viable in monolayer culture and readily detached from
      laminin as a substrate. The expression of beta1 integrin in GFAP-positive
      fibrosarcoma cells was decreased following heavy metal induction by Western blot
      analyses. In contrast, the expression of alpha2 integrin was increased whereas
      alpha5 integrin was unchanged in HT-1080 cells following the induction of GFAP.
      Gelatin zymography showed that 72 kDa collagenase was less expressed in GFAP
      induced clones than in controls. Our data suggest that the forced expression of
      the intermediate filament, GFAP, in HT-1080 cells may modulate cell adhesion to
      different ECM substrates through alterations in expression of integrins.

PMID- 11295053
TI  - Cell cycle arrest mediated by a pyridopyrimidine is not abrogated by over
      expression of Bcl-2 and cyclin D1.
AB  - Inhibition of cyclin dependent kinases (Cdks) is of pivotal importance in tumor
      cell biology as these kinases are the drivers of cell proliferation. This
      inhibition can be achieved either by naturally occurring biological proteins or
      by small molecule compounds. They cause cell cycle arrest and/or apoptosis
      depending upon the specificity and efficacy of the inhibitor in question. We have
      reported earlier that specific pyridopyrimidines (novel Cdk inhibitors) cause
      cell cycle arrest in mink lung epithelial cells and the arrest is abrogated by
      over-expression of Cdk4. In contrast, we show here that one of these inhibitors
      effectively maintains cell cycle arrest in a leukemic or a breast cancer cell
      line even after the respective cells over-express an oncogene, either Bcl-2 or
      cyclin D1. However, in the leukemic cells, Bcl-2 over-expression suppresses
      apoptosis induced by the pyridopyrimidine. Thus, novel Cdk inhibitors can prove
      to be useful chemical genetics tools for understanding the underlying mechanisms
      of growth arrest and/or apoptosis in normal versus tumor cells. This could also
      lead to the development of improved inhibitors of cell proliferation.

PMID- 11295054
TI  - Detection of MMTV-like LTR and LTR-env gene sequences in human breast cancer.
AB  - We have previously reported, using the polymerase chain reaction (PCR), the
      presence of a 660 bp sequence homologous to the env gene of MMTV in 38% of the
      human breast cancers studied, but not in normal breasts nor in other tumors or
      tissues. We have now investigated the presence of MMTV-like LTR sequences in
      human breast cancer and normal breast tissue. Primers were selected to amplify a
      630 bp sequence homologous to MMTV, but not to the endogenous retrovirus HERV
      K10. This sequence was detected in 41.5% of the breast cancers and none of the
      normal breasts. A larger 1.2 kb LTR fragment was also amplified with high
      homology to MMTV. Finally, a 1.6 kb fragment containing env and LTR sequences was
      amplified, cloned and sequenced from breast cancer DNA. The human LTRs were
      highly homologous to MMTV contain enhancer and promoter elements, the
      glucocorticoid responsive element (GRE) and the superantigen (Sag) sequences.
      Presence of functional sequences implies involvement in transcriptional
      regulation, whereas presence of an env-LTR sequence indicates contiguity within
      the genome of a potential provirus. Their presence in breast cancer DNA, but not
      in normal tissue, suggest an exogenous origin.

PMID- 11295055
TI  - Divergence in distribution and prognostic significance of major basement
      components in laryngeal carcinomas.
AB  - In previous studies, we demonstrated a loss of major basement membrane (BM)
      components in laryngeal squamous cell carcinomas and provided initial evidence
      that this was of potential prognostic significance. In our current study, we
      extended the panel of BM antibodies and enlarged our study group in order to
      perform a multivariate statistical analysis. We analyzed 26 laryngeal squamous
      cell carcinomas immunohistochemically for the distribution of the BM-components
      collagen IV, collagen VII, laminin-1, laminin-5, perlecan and fibronectin. The
      resulting data were correlated with clinical prognostic factors and statistical
      correlation coefficients were determined for independent uni- and multivariate
      analysis. All carcinomas analyzed revealed defects of the peritumoral BM with
      more extensive loss of collagen VII than collagen IV, laminin-1, perlecan and
      fibronectin. Laminin-5 in contrast was present even in poorly differentiated
      tumors showing an enhanced intracytoplasmatic staining in the tumor cells.
      Furthermore, our statistical analysis did not show independent prognostic
      significance of any of the BM-components. Our observations indicate a divergence
      between the loss of several major BM-components (collagens IV, VII, laminin-1,
      perlecan) and an enhanced deposition of laminin-5. This suggests a severely
      altered cell-matrix interaction, since laminin-5 links the collagen VII
      containing anchoring fibrils to cell receptors of the integrin type.

PMID- 11295056
TI  - Characterization of CD44 splicing patterns in normal keratinocytes, dysplastic
      and squamous carcinoma cell lines.
AB  - The CD44 glycoprotein is spliced from a complex gene of 10 constitutive and 10
      variant exons. In this study, CD44 splicing patterns and intron 9 retention were
      investigated by exon-specific RT-PCR for variant exons v1-v10 and intron 9 in
      normal, immortalized, dysplastic and malignant keratinocytes. Expression of
      product was determined immunohistochemically for some of the exons. Normal
      keratinocytes showed one major transcript including exons v2-v10 and 3 minor
      transcripts. No lines showed a normal CD44 splicing pattern but rather a variety
      of truncated transcripts of contiguous variant exons which overall correlated
      with expression. Squamous cell carcinoma (SCC)-4 and SCC-9 lines showed
      relatively normal transcripts although protein was expressed only by SCC-9. SCC
      12B2, SCC-15, SCC-25 and SCC-27 showed a series of shorter overlapping
      transcripts, with loss of exons v8-v10 in the major transcripts. Intron 9 was not
      retained in normal keratinocytes or cell lines. Despite the fact that
      keratinocytes constitutively express all variant exons, splicing patterns are
      distinctly abnormal and merit investigation as potential markers for epidermal
      and oral squamous malignancy.

PMID- 11295057
TI  - Potentiation of antitumor activity of irinotecan by chemically modified
      oligonucleotides.
AB  - Co-administration of synthetic chemically modified oligonucleotides with
      irinotecan, a selective topoisomerase I inhibitor, provided a significant
      enhancement in the antitumor activity of irinotecan. The enhancement of antitumor
      activity of irinotecan with co-administration of chemically modified
      oligonucleotides was observed in several tumor models--pancreatic cancer (Panc
      1), colon cancer (HCT-116) and melanoma (A375). Inhibition of tumor growth in all
      three models required the co-administration of irinotecan and chemically modified
      oligonucleotides, but was independent of the nucleotide sequence of the
      oligonucleotides. The potentiation of antitumor activity was dependent on the
      dose of irinotecan and chemically modified oligonucleotides administered. The
      enhancement of antitumor activity of irinotecan was also observed by co
      administration of a phosphorothioate oligonucleotide, however, to a lesser extent
      than did chemically modified oligonucleotides, suggesting that metabolic
      stability of the oligonucleotide contributes to the enhancement of antitumor
      activity seen with irinotecan. The co-administration of dextran sulfate sodium
      with irinotecan showed insignificant potentiation of antitumor activity of
      irinotecan, suggesting that the enhancement of antitumor activity of irinotecan
      observed was not a result of polyanionic characteristic of oligonucleotides. Co
      administration of irinotecan and chemically modified oligonucleotides did not
      result in increased toxicity in the tumor models studied. Potentiation of
      antitumor activity of irinotecan observed with co-administration of
      oligonucleotides suggests that the oligonucleotides affect the pharmacokinetics
      and/or metabolism of irinotecan. The use of chemically modified oligonucleotides
      together with irinotecan may increase the therapeutic index of irinotecan in
      cancer patients and continued development of such agents should be considered.

PMID- 11295058
TI  - Effects of cyclic adenosine-monophosphate on growth and PSA secretion of human
      prostate cancer cell line.
AB  - Prolonged increase of cyclic adenosine-monophosphate (cAMP) level in the culture
      medium of a well differentiated human prostatic cancer cell (LNCaP) inhibits
      cellular growth and stimulates PSA secretion. The differentiation of the cells
      tested was documented by their responsiveness to androgens and the ability to
      synthesize cellular markers of differentiation (PSA). The raise in cAMP level was
      produced by dibutyryl cyclic AMP (DBcAMP) or by agents acting at distinct levels
      in the pathway of cAMP generation (forskolin) or degradation (IBMX). Each of
      these three agents in a range of concentrations between 10-4-10-6 M had an
      inhibitory effect on the growth which is dose and time-dependent. The inhibition
      was reversible as demonstrated by complete restoration of cell growth soon after
      the withdrawal of the substances from the culture medium. When cAMP levels in
      culture medium was raised, an increase in PSA content was observed. However, the
      effects of cAMP on PSA content was not due to increase in PSA synthesis, since
      simultaneous measurement of secreted and cellular PSA indicated that the
      principal effect of the cyclic nucleotide was to enhance the secretion of stored
      PSA. Furthermore the inhibition of cellular growth by cAMP suggests new
      approaches in prostatic carcinoma therapy.

PMID- 11295059
TI  - Protein kinase C activation by PMA rapidly induces apoptosis through caspase
      3/CPP32 and serine protease(s) in a gastric cancer cell line.
AB  - Phorbol 12-myristate 13-acetate (PMA) rapidly induced cell death in SNU-16
      gastric adenocarcinoma cells. DNA ladder formation and caspase-3/CPP32 activation
      were observed in PMA treated cells indicating that PMA induces apoptosis. z-DEVD
      fmk, specific inhibitor of caspase-3/CPP32, inhibited the induction of apoptosis
      by PMA, demonstrating that caspase/CPP32 are critically involved in PMA-induced
      apoptosis. The serine protein inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride
      effectively blocked apoptosis, and also prevented caspase-3/CPP32 activation.
      Go6983, a specific inhibitor of PKC, almost completely suppressed apoptosis and
      caspase-3/CPP32 activation. Furthermore, 1,2-dihexanoyl-sn-glycerol, an
      endogenous activator of PKC, induced apoptosis detected by DNA fragmentation and
      Hoechst 33258 nuclear staining. From these results, we conclude that PMA is not
      only a tumor promoter, but can also induce apoptosis in gastric cancer cells. PMA
      induced apoptosis appears to be mediated through activation of protein kinase C,
      and the activation of serine protease(s) and caspase-3/CPP32 may be the molecular
      mechanisms by which PMA induces apoptosis.

PMID- 11295060
TI  - CA19-9 epitope a possible marker for MUC-1/Y protein.
AB  - It has been reported that MUC-1 molecules devoid of the tandem repeat region (MUC
      1/Y) are detected preferentially in carcinoma cells and are associated with their
      progression. However, its clinical significance is still unknown. We constructed
      a mouse colon adenocarcinoma cell line (MC-38) transduced with either MUC-1/Y
      cDNA defecting the tandem repeat region (Y-MC-38) or MUC-1/R cDNA containing ten
      tandem repeats (R-MC-38). RT-PCR of mRNAs derived from Y-MC-38 cells using the
      specific primers to MUC-1/Y mRNAs, proved the existence of 600 bp RT-PCR products
      generated only from MUC-1/Y mRNAs. DF3 and CA19-9 epitopes out of the MUC-1
      related tumor-associated antigens, have been reported to be involved in the
      prognosis of cancer patients. We examined the expression of DF3 and CA19-9
      epitopes on Y-MC-38 and R-MC-38 cells. Fluorescence-activated cell sorting (FACS)
      analysis of R-MC-38 and Y-MC-38 cells using two monoclonal antibodies against DF3
      (mAb DF3) and CA19-9 (mAb CA19-9) epitopes revealed that R-MC-38 cells expressed
      DF3 but not CA19-9 [DF3(+)CA19-9(-)], while Y-MC-38 cells expressed CA19-9 but
      not DF3 [DF3(-)CA19-9(+)]. On Western blot, a 40 kDa protein product was
      recognized by mAb CA19-9 but not by mAb DF3 on cell lysates of Y-MC-38 cells,
      whereas a 70 kDa protein product was recognized by mAb DF3 but not by mAb CA19-9
      on the cell lysates of R-MC-38. Further, we analyzed the expression of MUC-1/Y
      mRNAs by RT-PCR on various human cancer cell lines: the gastric cancer cell line
      AZ521, the pancreatic cancer cell lines PANC-1 and Capan-1, the gall bladder cell
      line GBK-1, the breast cancer cell line MCF-7, and the colon cancer cell lines HT
      29 and Colo205. HT-29 and Capan-1 cells producing the 600 bp RT-PCR product, were
      positive for mAb CA19-9. These results demonstrate that CA19-9 epitope is
      produced only on MUC-1/Y core protein, suggesting that CA19-9 epitope may be a
      specific marker for MUC-1/Y protein.

PMID- 11295061
TI  - Basic fibroblast growth factor in mesothelioma pleural effusions: correlation
      with patient survival and angiogenesis.
AB  - The expression of angiogenic factors may represent useful markers for diagnosis
      and prediction of disease outcome. Basic fibroblast growth factor (b-FGF) is a
      potent angiogenic factor which promotes in vitro growth of endothelial cells and
      in vivo vessel formation. We investigated the expression of b-FGF in patients
      affected with malignant and non-malignant pleural diseases and presenting
      clinically with non-specific signs and symptoms. We also studied the
      relationships between the expression of b-FGF in patients with malignant pleural
      mesothelioma (MM) and tumour aggressiveness, assessed as tumour vessel density
      (TVD), or patient survival. Basic-FGF was measured by immunoassay in the serum
      and pleural effusions (PE) of 37 patients. Of these, MM was diagnosed in 15/37
      patients while the remaining patients had either peripheral lung adenocarcinoma
      (PLA) or benign inflammatory pleural disease (BPD). The mean b-FGF level measured
      8.5+/-6.1 pg/ml in the PE of the malignant group (MM + PLA) and 23.9+/-19.8 in
      the PE of the non-malignant group (BPD) (p=0.001). The mean b-FGF level was
      significantly lower in the PE of MM patients (6.9+/-5.2 pg/ml) compared to BPD
      patients (p=0.004). Linear regression analysis showed a significant inverse
      correlation (r=-0.59; p=0.041) between b-FGF levels found in MM PE and patient
      survival. A noteworthy relationship between high serum b-FGF levels and reduced
      survival was also observed (r=-0.57; p=0.052). Interestingly, both serum (r=0.48;
      p=0.114) and PE (r=0.26; p=0.413) b-FGF levels in MM patients correlated poorly
      with TVD. Our data indicate that b-FGF is significantly more expressed in non
      malignant compared to malignant PE, this difference being particularly evident
      between MM and BPD. Our results also suggest that high b-FGF levels correlate
      with poor MM patient survival through mechanisms which may be independent of b
      FGF angiogenic potential.

PMID- 11295062
TI  - In vivo photodynamic activity of hypericin in transitional cell carcinoma bladder
      tumors.
AB  - In a recent clinical study, we showed that hypericin accumulates selectively in
      urothelial lesions of the bladder following intravesical administration of the
      compound in patients. This observation infers that hypericin, a potent
      photosensitizer, could be used as a selective photodynamic therapy (PDT) tool
      against superficial bladder cancer. In the present study we investigated the in
      vivo PDT activity of hypericin in transition cell carcinoma (TCC) tumors of the
      bladder. Both the distribution and tumor PDT response were carried out using
      subcutaneous heterotopic AY-27 TCC tumors in syngeneic rats. For both PDT and
      distribution studies, hypericin (1 or 5 mg/kg) was injected intravenously 0.5, 6
      or 24 h before PDT or distribution evaluation. The data show that hypericin is a
      potent photosensitizer in the treatment of TCC tumors in vivo and that the
      interval between drug administration and photo-irradiation has a dramatic effect
      on the PDT outcome. Using a 0.5 h interval between drug administration and photo
      irradiation the tumor regrowth study indicated that no tumor mass could me
      measured 9-10 days after PDT. On the contrary, lengthening the time interval
      between drug administration and photo-irradiation resulted in a gradual loss of
      PDT efficiency in these tumors. For instance, while the 6 h drug interval
      protocol produced a moderate PDT activity in which the tumor sizes decreased to
      about 50% of their original sizes 11-16 days after photo-irradiation, the 24 h
      interval protocol was even less effective. The distribution data indicate that
      the PDT efficiency of hypericin in TCC tumors corresponded to the plasma
      concentrations rather than to the over all concentrations in the tumor. It is
      therefore conceivable that the mechanism of PDT efficacy of hypericin in TCC
      tumors is through indirect (vascular effects) rather than through direct effects
      (cellular destruction) of hypericin in these tumors. In conclusion, our data
      indicate that hypericin is a potent photosensitizer against AY-27 TCC tumors and
      that the PDT efficacy of hypericin is largely determined by photosensitizer
      distribution in the tumor at the time of photo-irradiation.

PMID- 11295063
TI  - Motility factors identified in supernatants of human cholangiocarcinoma cell
      lines.
AB  - Motility factors, e.g. SF/HGF (scatter factor/hepatocyte growth factor) or AMF
      (autocrine motility factor) can influence the migration of tumor cells in vitro
      and may facilitate invasive growth and metastases in vivo. The production of
      motility factors was studied in cell lines derived from human
      cholangiocarcinomas. Culture supernatants from 5 different cholangiocarcinoma
      cell lines (EGI-1, RPMI 7451, MZ CHA-1, MZ CHA-2 and MZ CHA-3) were analyzed in
      scatter assays with NRK and MDCK cells as indicator cells which react with
      cellular migration in the presence of motility factors. Culture supernatants from
      4 of the 5 cell lines investigated induced migration of the indicator cells thus
      demonstrating the production of motility factors. Three of the cell lines (MZ CHA
      1, MZ CHA-2, RPMI 7451) produced a factor with a molecular weight ranging between
      50 and 100 kDa, EGI-1 cells secreted a factor with a molecular weight >100 kDa.
      None of the factors was identical to HGF as demonstrated by the lacking
      reactivity in a HGF specific ELISA and by the inability to induce scattering of
      HPAF indicator cells like HGF. Similar to SF/HGF, the activity of the EGI-1
      factor was inhibited by the proteoglycan heparin and stimulated the chemotactic
      cell migration, but in contrast to SF/HGF it could not induce invasive growth of
      NRK cells. The production of scatter factors could be involved in tumor
      progression and formation of metastases of cholangiocarcinomas.

PMID- 11295064
TI  - Recombinant PAI-1 inhibits angiogenesis and reduces size of LNCaP prostate cancer
      xenografts in SCID mice.
AB  - To understand the fundamental determinants of urokinase plasminogen activator
      (uPA) driven angiogenesis in cancer we studied how inhibition of uPA activity
      could reduce neovascularization and consequently reduce tumor size in
      experimental animals. Proteolytic enzymes are required to mediate tumor cell
      invasion to adjacent tissues and initiate the metastatic process. Many different
      human cancers commonly overexpress the urokinase plasminogen activator system,
      one of the proteolytic enzyme systems. Reduction of urokinase activity in cancer
      cells is evidently associated with diminished invasion and metastasis. However,
      it has been shown recently that inhibitors of uPA could reduce tumor size also.
      The mechanism of action leading to decline in tumor growth rate is not clear.
      Proteolysis is responsible for degradation of proteins, for invasion or
      metastasis, but not for the proliferate properties of the cancer cells. It is
      difficult to envision that diminishing the size of tumor is due to simply
      blocking of uPA activity of cancer cells. Instead, inhibitors of uPA may be
      interacting with the elements of the extracellular matrix, such the neovascular
      bed surrounding tumors that has been reported to contain high amounts of uPA and
      its receptor. Overall these data strongly suggest that inhibitors of urokinase
      limit cancer growth by inhibiting angiogenesis. However, it is possible also that
      uPA inhibitors could act on cancer cells directly or prevent angiogenesis by
      alternative mechanisms that are not related to uPA inhibition. Therefore, we
      examined if plasminogen activator inhibitor (PAI-1) could limit angiogenesis. If
      it does, it will provide definitive evidence of uPA/PAI-1 involvement in
      reduction of cancer growth. Indeed, our study demonstrates that exogenously
      applied 14-1b PAI-1 is a powerful inhibitor of angiogenesis in three different in
      vitro models and is a powerful anti-cancer agent in a SCID mice model inoculated
      with human LNCaP prostate cancer cells.

PMID- 11295065
TI  - Inverse correlation of apoptotic and angiogenic markers in squamous cell
      carcinoma of the head and neck.
AB  - Angiogenesis is essential for tumour growth and metastasis. The induction of
      tumour vascularization is mediated by the release of angiogenic peptides. Among
      these factors, basic fibroblast growth factor (bFGF), vascular endothelial growth
      factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are thought to be the most
      important. Previous experimental studies indicate that the process of apoptosis,
      the programme of cell death, may be related to angiogenesis in head and neck
      carcinogenesis. Therefore, cryostat sections of 49 head and neck squamous cell
      carcinomas (HNSCC) were investigated immunohistochemically for pro-apoptotic
      factors caspase-3 and Fas ligand (FasL) using a standard streptavidin-biotin
      complex procedure. Expression of bFGF, VEGF and MMP-9 served as angiogenic
      markers. Additionally, intratumoral microvascular density (MVD) was counted by
      immunostaining of endothelial cells using anti-vWF antibody. Comparing the
      expression of apoptotic and angiogenic factors, a statistically significant
      inverse correlation of caspase-3 expression and VEGF and MMP-9 expression was
      found. Concerning FasL, the correlation of its expression with expression of
      VEGF, bFGF and MMP-9 was inversely correlated. With respect to vWF
      immunostaining, statistical analysis gave a clear inverse correlation between the
      tumour vascularity and the expression of FasL (p = 0.0008) and caspase-3 (p =
      0.0068). Our results suggest that HNSCC tumour angiogenesis contributes to a
      reduction of apoptosis in tumour cells. This may be explained by the activation
      of pro-apoptotic factors caused by hypoxia.

PMID- 11295066
TI  - Expression of Trk tyrosine kinase receptor is a biologic marker for cell
      proliferation and perineural invasion of human pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a widely known severe malignancy with
      a poor prognosis. Perineural invasion extending to the extra-pancreatic nerve
      plexus, a significant concern in the treatment is frequently present in this
      cancer. We analyzed immunohistochemical expression of neurotrophins (NGF, BDNF,
      NT-3) and the cognate receptors, Trk tyrosine kinase receptor family (TrkA, B, C)
      and p75NGFR in 28 surgically resected PDAC specimens. A comparative study between
      several clinicopathologic factors and Trk receptors revealed a significant
      correlation between increased expression of TrkA and cancer proliferation, as
      well as TrkC and cancer invasion, including venous and perineural invasion. The
      present findings revealed a novel mechanism in PDAC progression that is mediated
      via a NTs-Trk interaction.

PMID- 11295067
TI  - MUC1 and MUC2 expression in human gallbladder carcinoma: a clinicopathological
      study and relationship with prognosis.
AB  - Mucins are a group of high molecular weight glycoproteins consisting of a mucin
      core protein and O-linked carbohydrates. To date, nine apomucins (MUC1-8, and
      MUC5B) have been identified. Recent studies have demonstrated that MUC1 is
      expressed in tumors of various human organs, and may function as an anti-adhesion
      molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. MUC2 is
      a major secreted mucin of colon and is known to be expressed in cells showing
      intestinal metaplasia in the stomach and other organs. MUC2 expression in the
      mucosal epithelia is an apparently abnormal phenomenon related to the neoplastic
      process. In this study, we examined MUC1 and MUC2 expression in human gallbladder
      adenocarcinoma and its clinicopathological significance and relationship with the
      prognosis of the patients. MUC1 immunoreactivity was detected not only in the
      cancer cells but also in the cancer stroma. Cytoplasmic MUC1 expression was
      significantly relation to lymphatic invasion and lymph node metastasis (p <
      0.001), and was associated with a poor outcome. In contrast, MUC2 was rarely
      expressed in gallbladder carcinomas, and its immunoreactivity was detected only
      in the cancer goblet cells. Overexpression of MUC2 was not significantly related
      to lymphatic invasion or lymph node metastasis, or prognosis of patients. These
      observations suggested that MUC1 expression plays a more important role than MUC2
      expression in cancer cell growth and metastasis of human gallbladder
      adenocarcinomas.

PMID- 11295068
TI  - Biological role of thymidine phosphorylase in human astrocytic tumors.
AB  - Thymidine phosphorylase (TP) has strong angiogenic activity and is overexpressed
      in a wide variety of malignant tumors. To elucidate the role of TP in human
      astrocytic tumors, we immunohistochemically investigated the expression of TP in
      62 astrocytic tumors (12 astrocytomas, 12 anaplastic astrocytomas and 38
      glioblastomas). Fifty-five astrocytic tumors (88.7%) were immunopositive for TP.
      The level of TP-expression was significantly correlated with the malignancy grade
      of astrocytic tumors; most of malignant gliomas highly expressed TP, while a
      small number of cells were positive in low grade astrocytomas (p < 0.001). Using
      double-immunostaining, we clarified that TP-expression was predominantly
      detectable in macrophages. There was no significant correlation between MIB-1
      labeling index and TP-expression. However, TP-expression and the microvessel
      density were well correlated. These suggest that TP, mainly produced by the
      infiltrated macrophages, may play an important role in the progression of
      astrocytic tumors via neovascularization. Inhibitor of TP may represent a
      therapeutic modality for treating malignant gliomas.

PMID- 11295070
TI  - Hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines with
      different radiothermosensitivity in vitro.
AB  - We investigated cell susceptibility to hyperthermia-induced apoptosis in two rat
      yolk sac tumor cell lines (RYSTs) and attempted to correlate this with the known
      potentially relevant molecular determinants of apoptosis, p53 protein status, Bcl
      2 family of proteins and heat shock proteins (Hsp). Parent cell line, NMT-1
      (carrying wild-type p53 gene) was radiosensitive but thermoresistant compared to
      the variant cell line, NMT-1R (mutated type p53), which was isolated from NMT-1
      by repeated radiation exposure. Induction of apoptosis by hyperthermia at 43
      degrees C was morphologically detected in both RYSTs using hematoxylin and eosin,
      and TUNEL staining and additionally confirmed by DNA ladder formation (the
      cleavage of DNA into oligonucleosomal fragments). Western blot analysis showed an
      increase in expression of p53, p21WAF1/CIP1, Hsp70 proteins in both cell lines
      after heat-shock at 43 degrees C for 30 min. Hsp90 expression increased in NMT-1
      but was not affected by heating in NMT-1R cells, whereas hyperthermia exerted no
      effect on the endogenous expression of Bax. Bcl-2 protein could not be detected
      in either RYST. These results suggest that hyperthermia induced apoptosis in both
      NMT-1 and NMT-1R and apoptosis in RYSTs may be independent of p53-dependent
      signaling pathway.

PMID- 11295069
TI  - Molecular markers and prediction of response to chemoradiation in rectal cancer.
AB  - Preoperative chemotherapy and radiation (chemoradiation) are increasingly used in
      the treatment of advanced rectal carcinoma to downstage the tumor so that a
      sphincter sparing procedure is used. This treatment modality has also resulted in
      not only local disease control but also decreased metastasis and increased
      survival. It is well known that with standard chemoradiation some tumors show
      marked pathologic response, while others remain non-responsive. Identification of
      tumor markers that can predict responsiveness to chemoradiation is extremely
      useful to avoid unnecessary preoperative treatment. To understand the role of
      thymidylate synthase (TS), p53 and Bcl-2 proteins, if any, in tumor
      response/resistance to chemoradiation, we examined pretreatment biopsy material
      obtained from 12 responsive and 13 non-responsive patients by
      immunohistochemistry. TS was undetectable in 11 of 12 (92%) responsive tumors and
      overexpressed in only 1 tumor (8%); whereas, p53 or Bcl-2 was overexpressed in 8
      tumors (66%). In the non-responsive group of 13 tumors, overexpression of TS, p53
      and Bcl-2 was observed in 7, 5 and 6 tumors, respectively. In 6 non-responsive
      tumors in which TS was undetectable, 5 tumors contained high levels of p53 or Bcl
      2. These results indicate that level of TS in tumors is the best predictor of
      sensitivity or resistance to chemoradiation. No such correlation between
      overexpression of p53 and Bcl-2 and response to chemoradiation is observed.

PMID- 11295071
TI  - p53 mutation found to be a significant prognostic indicator in distal colorectal
      cancer.
AB  - There has been few reports describing that the prognostic significance of p53
      alteration in colorectal tumors depended on the site of origin. Therefore, in
      this study, we examined whether there is a valid association between the p53
      alterations and the prognosis of colorectal cancer patients, especially distal
      colorectal cancer cases. Tumor samples were collected from 110 patients resected
      for colorectal cancer between 1989 and 1997. The entire coding region of the p53
      gene was analyzed by automated direct sequencing. In addition, the DO-7
      monoclonal antibody was used in the immunohistochemical (IHC) assessments. By the
      Cox univariate analyses in all tumors, Dukes' stage, lymph node metastasis, liver
      metastasis, p53 mutation and p53 protein overexpression were significant
      predictors of survival. The cases without p53 mutation showed significantly
      improved prognosis compared to the cases with p53 mutation (p = 0.0085). In
      distal tumors, Dukes' stage, liver metastasis, p53 mutation and p53 protein
      overexpression were significant predictors of survival. Multivariate analysis of
      all tumors, p53 mutation and liver metastasis were independent indicators of poor
      survival (p = 0.0223 for p53 mutation, p = 0.0254 for liver metastasis). Also in
      distal tumors, p53 mutation was an independent indicator (p = 0.0011).
      Furthermore, the relative risk associated with p53 mutation in distal tumors was
      much higher than that in all tumors (8.260 vs. 1.796). However, p53 protein
      overexpression was not an independent indicator of survival in all tumors as well
      as distal tumors (p = 0.1918 in all tumors, p = 0.0607 in distal tumors). In
      proximal tumors, p53 mutation was not an independent indicator (p = 0.6673). We
      think that p53 mutation is a very useful prognostic indicator when distal
      colorectal cancers are considered.

PMID- 11295072
TI  - Progression of prostate cancer: diagnostic and prognostic utility of prostate
      specific antigen, alpha2-macroglobulin, and their complexes.
AB  - We previously reported cases of advanced prostate cancer (PCa) in which serum
      alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than
      approximately 50 mg/dl whereas serum prostate-specific antigen (PSA) levels were
      remarkably increased. These cases were not complicated with disseminated
      intravascular coagulation (DIC). In this study, we measured serum PSA and alpha2M
      in 108 patients with either benign prostatic hyperplasia (BPH) or PCa to
      elucidate the relationship between PSA, i.e. the serum protease derived from the
      prostatic tissue, and alpha2M, i.e. the protease inhibitor that was the most
      abundantly contained in serum. alpha2M was determined by ELISA, total PSA and PSA
      alpha1-antichymotrypsin (PSA-ACT) by EIA, and free-PSA by RIA in 44 patients with
      untreated BPH and 64 patients with untreated PCa. The ready association of
      alpha2M and PSA was assessed using Western blotting to identify complexes of the
      two. Levels of total serum PSA correlated positively with those of PSA-ACT in PCa
      (r = 0.99, p < 0.001), and both levels increased with advancing stage of disease.
      In contrast, the serum-free PSA/total PSA ratio (free/total PSA) and alpha2M
      levels decreased as the disease progressed. However, only the free/total PSA
      ratio attained significant difference for localized cancer in stage T1,2 versus
      BPH (p < 0.05). In stage M1b PCa, in which serum PSA levels were very high, there
      was a negative correlation between the total PSA and alpha2M values (r = -0.57, p
      < 0.05). In addition, serum alpha2M levels tended to decrease with progression of
      PCa. Serum total PSA levels correlated tightly with serum PSA-ACT levels. It is
      suggested that PSA is usually complexed with ACT in the serum. Free/total PSA was
      useful for differential diagnosis between early cancer and BPH. Levels of serum
      alpha2M of less than 50 mg/dl in PCa patients may indicate a possibility of bone
      metastases.

PMID- 11295073
TI  - The complementary role of beta-catenin in diagnosing various subtypes of renal
      cell carcinomas and its up-regulation in conventional renal cell carcinomas with
      high nuclear grades.
AB  - beta-catenin is a kind of cytoplasmic protein involved in cell adhesion and
      signal transduction. This study investigated its expression in various subtypes
      of renal cell carcinomas (RCCs) using an immunohistochemical staining method.
      beta-catenin expression was assessed from staining frequency and staining score.
      Staining score was performed by evaluating both staining percentage and
      intensity. All subtypes of RCCs reacted positively with beta-catenin. However,
      the positive frequency and staining score in papillary and chromophobe RCCs were
      significantly higher than those in conventional RCCs (p < 0.05). In addition, in
      conventional RCCs, the positive frequency and staining score of beta-catenin
      showed a significant difference between nuclear grades I/II and grade III (p <
      0.05). Therefore, it may indicate that beta-catenin can serve as a complementary
      tool to distinguish conventional RCCs from chromophobe RCCs. In conventional RCCs
      with low nuclear grades, beta-catenin expression is generally down-regulated,
      while it appears to be preserved in those with high nuclear grades.

PMID- 11295074
TI  - Membrane fluidity correlates with liver cancer cell proliferation and
      infiltration potential.
AB  - We developed a method to measure membrane fluidity of living cancer cells in two-
      and three-dimensional cultures, and found that there was a close relationship
      between the membrane fluidity of cancer cells and their proliferative and
      infiltrative ability. Membrane fluidity is thus a promising indicator of the
      probability of cancer recurrence.

PMID- 11295075
TI  - P53 mutations in Ewing's sarcoma.
AB  - The p53 tumor suppressor gene is one of the most frequently altered genes in
      human malignancies. To explore the implication of p53 alteration in Ewing's
      sarcoma, we analyzed the deletion and sequence alterations of p53 and abnormal
      amplification of MDM2, which acts as a functional inhibitor of p53, in 35 tissue
      specimens. Quantitative genomic PCR analysis showed that 2 of 35 tumors have
      extremely low levels of the p53 gene, indicating a homozygous deletion of the
      gene. Mutational analysis of exons 4 to 9 of p53 by PCR-SSCP revealed that 3 of
      35 tumors carry sequence alterations in exons 5 or 8, and DNA sequencing analysis
      identified missense point mutations at codon 132 (AAG-->ATG, lysine-->methionine)
      and codon 135 (TGC-->TCC, cystein-->serine) in exon 5, and codon 287 (GAG-->GTG,
      glutamic acid-->valine) in exon 8 from these tumors. No abnormal amplification of
      the MDM2 gene was recognized. Taken together, our data demonstrate that p53 is
      genetically altered in a small fraction of Ewing's sarcoma.

PMID- 11295076
TI  - Heparanase expression in clinical digestive malignancies.
AB  - Recently, mammalian heparanase was cloned, and its probable function in tumor
      progression was reported. However, its expression in human clinical cancers has
      not been fully studied. Thus we determined the heparanase mRNA expression in 30
      esophageal cancer cell lines and 144 clinical samples including 38 esophageal
      squamous cell carcinomas, 71 gastric adenocarcinomas, and 35 colorectal
      adenocarcinomas. The fresh surgical specimens of cancer tissue (T) and its paired
      normal tissue (N) were used. The heparanase mRNA was evaluated by reverse
      transcriptase-polymerase chain reaction, and the T/N expression ratio was
      determined in clinical cases. All 30 esophageal cancer cell lines expressed
      heparanase mRNA. The T/N ratio was determined as high (> or =1.3), equal (0.8
      approximately 1.2) or low (< or = 0.7) in each clinical case. In cases of
      esophageal cancer, 7 showed high, 10 equal and 21 low expression. In cases of
      colorectal cancer, 3 showed high, 16 equal and 16 low expression. On the other
      hand, 42 showed high, 22 equal and 7 low expression in cases of gastric cancer.
      The frequency of high expression cases was greater in gastric cancer than in
      esophageal or colorectal cancers (p < 0.05). There were no differences in
      clinicopathologic factors including prognosis between high and low expression
      cases of each cancer. Our mRNA study of heparanase indicated that its expression
      status was different among gastrointestinal cancers. The clinical and
      pathological impact was low compared to other proteinases, although further
      studies are recommended for final conclusion.

PMID- 11295077
TI  - Effect of a combined administration of 5-fluorouracil and medroxyprogesterone
      acetate on pyrimidine nucleoside phosphorylases and thymidylate synthetase in
      7,12-dimethylbenz.
AB  - The effect of a combined therapy of medroxyprogesterone acetate (MPA) and 5
      fluorouracil (5-FU) on tumor size, pyrimidine nucleoside phosphorylase (PyNPase)
      activity, and thymidylate synthetase (TS) activity was examined in Sprague-Dawley
      (SD) rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. MPA
      augmented the antitumor activity of 5-FU and protected against body weight-loss
      due to 5-FU administration. PyNPase activity of both the MPA group and the MPA+5
      FU group tended to increase compared with that of the 5-FU alone group. TS
      inhibition levels in the MPA+5-FU group tended to increase compared with those in
      the 5-FU alone group. These results indicate that MPA tended to augment antitumor
      activity of 5-FU and to reduce the side effects caused by 5-FU.

PMID- 11295078
TI  - Correlation of DNA synthesis-inhibiting activity and the extent of transmembrane
      permeation into tumor cells by unsaturated or saturated fatty alcohols of graded
      chain-length upon hyperthermia.
AB  - The carcinostatic activity has been studied for fatty acids of diverse species
      but scarcely for fatty alcohols. Three unsaturated fatty alcohols at 35-50 microM
      inhibited DNA synthesis and the proliferation of tumor cells by a combination
      with hyperthermia to greater extents in the order: oleyl (C18:1)-> linoleyl
      (C18:2)-> alpha-linolenyl (C18:3) alcohol, which is an order inverse to that
      known for the corresponding fatty acids (4). In contrast, two saturated fatty
      alcohols, palmityl (C16:0)- and stearyl (C18:0) alcohols, did not inhibit at the
      same concentrations. At 100 microM, palmityl alcohol inhibited, whereas stearyl
      alcohol did not. The effective fatty alcohols appreciably permeated the cells.
      The inhibition of the unsaturated fatty alcohols on DNA synthesis and
      proliferation was nearly proportional to the amount of their intercellular
      accumulation at 37 degrees C or 42 degrees C; the most inhibitory, oleyl alcohol,
      was the most membrane-permeable, whilst inversely the least inhibitory, alpha
      linolenyl alcohol, was the least permeable. A proportional correlation was not
      observed for saturated fatty alcohols; palmityl alcohol underwent an approximate
      2-fold more abundant accumulation than other fatty alcohols, but was weakly
      inhibitory. Thus, oleyl alcohol may exert an antitumor action via appropriately
      efficient transmembrane permeation and a combination with hyperthermia.

PMID- 11295079
TI  - Ewing's sarcoma of bone: relation between clinical characteristics and staging.
AB  - Patients with metastatic Ewing's sarcoma of bone have a poor prognosis. A
      relation between clinical characteristics and presence of metastatic disease at
      diagnosis in patients with Ewing's sarcoma of bone was investigated. Data from
      618 patients [136 (22%) with metastases at diagnosis] registered at the authors'
      institution between April 1972 and December 1997 were collected. The distribution
      of several clinical and hematologic parameters in patients with metastases and
      those without metastases was analyzed, and clinical risk factors of metastatic
      disease at presentation were analyzed by means of multivariate logistic
      regression analysis. All the variables significant at the univariate analysis
      (age, fever, site, volume, lactic dehydrogenase, anemia, and interval between
      onset of symptoms and diagnosis) were considered in the multivariate analysis.
      Pelvic location of the tumor, high level of lactic dehydrogenase, presence of
      fever, an interval between onset of symptoms and diagnosis less than 3 months,
      and age older than 12 years were found to be risk factors of clinically evident
      metastatic disease. In the subset of patients with no risk factors the rate of
      metastatic disease at presentation was only 4%; in case of contemporary presence
      of two factors it was 23%, although it was almost double (44%) if three or four
      factors were present. Only six patients were positive for five factors and all of
      them had metastases at presentation. The parameters identified are clinical
      markers of Ewing's sarcoma having a particularly aggressive metastatic behavior.

PMID- 11295080
TI  - Abnormal expression of pan-ras, c-myc and tp53 in squamous cell carcinoma of
      cervix: correlation with HPV and prognosis.
AB  - The aim of this study is to assess, in squamous cell carcinoma of the cervix, the
      expression of pan-ras, c-myc and tp53 at protein level using an
      immunohistochemical (IHC) staining method. One hundred and seven patients with
      squamous cell carcinoma of the cervix were recruited. Fifty-four patients were of
      stage 1B/2A and 53 were of stage 2B and above. Positive IHC stainings of pan-ras,
      c-myc and tp53 proteins were detected in 80.4%, 32.7% and 25.2% of cases,
      respectively. No significant correlation between overexpression of pan-ras and c
      myc was detected. However, significantly higher percentages of overexpression of
      c-myc was found in association with overly expressed tp53 samples (p = 0.014).
      Human papillomavirus (HPV) was detected in 77.6% of cancers. HPV 16/18 was
      detected in 72% of cancers. Overexpression of pan-ras and c-myc had no
      correlation with HPV detection and stage. However, higher percentages of
      overexpression of tp53 were found in early stage disease (p = 0.017) and in HPV
      16/18 positive tumors (p = 0.006). Overexpression of pan-ras, c-myc and tp53
      alone or in more than one oncogenes had no prognostic significance on survival.

PMID- 11295081
TI  - Transformation-associated changes in gene expression of alternative splicing
      regulatory factors in mouse fibroblast cells.
AB  - Although the alternative splicing of various genes is a common phenomenon in
      tumorigenesis, little is known about the mechanism behind it. Recently, we found
      altered expression of splicing regulatory factors during two-step chemical
      transformation in vitro. However, it remains unknown whether such altered
      expression of splicing factors commonly occur during other modes of
      transformation. We have further investigated the expression of five splicing
      regulatory factors, heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and A2,
      alternative splicing factor/splicing factor 2 (ASF/SF2), spliceosome component of
      35-kDa protein (SC35) and 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65),
      using two series of clonally-derived mouse fibroblast cell lines, that were SV40
      large T transfectants (SV-T2 and NIH3T3/13C7) or c-erbB2 transfectants (A4).
      U2AF65 expression was increased (2.1- and 2.7-fold) in NIH3T3/13C7 and A4
      compared with the normal parental cells, respectively, and SC35 expression was
      increased 1.8- to 2.3-fold in all transformed cells. These results suggest that
      altered expression of some splicing regulatory factors may commonly occur during
      various modes of cellular transformation.

PMID- 11295082
TI  - Expression of receptor tyrosine kinase EphB4 and its ligand ephrin-B2 is
      associated with malignant potential in endometrial cancer.
AB  - The protein kinases includes many oncogenes and growth-factor receptors, as well
      as genes that are involved in cell cycle regulation. EphB4 receptors are a
      subfamily of receptor tyrosine kinases that are activated by ephrin-B2 ligands
      and are thought to play an important role in the development and oncogenesis of
      various tissues. However, very little experimental evidence exists to support
      this hypothesis. To elucidate the involvement of EphB4 and ephrin-B2 in
      endometrial carcinogenesis, we used fluorescent immunohistochemistry to analyze
      serial frozen sections of 20 endometrial carcinomas and 20 normal endometria for
      EphB4 and ephrin-B2 protein expression. We analyzed the relationship between the
      patient's characteristics and the percentages of EphB4- and ephrin-B2-stained
      cells. EphB4 expression was significantly associated with histological grade (p <
      0.001) and certain clinical stages. Ephrin-B2 Expression was significantly
      associated with the presence of invasion to > 1/2 myometrium (p = 0.002). Our
      results demonstrate that increased EphB4 and ephrin-B2 expression may reflect or
      induce in endometrial carcinomas increased potential for growth and
      tumorigenicity. Furthermore, these results suggest that EphB4 receptor kinase may
      modulate the biological behavior of endometrial carcinomas through autocrine
      and/or paracrine activation, which is caused by ephrin-B2 ligands that are
      expressed in the same or neighbouring cells by immunohistochemistry.

PMID- 11295083
TI  - Obstructive jaundice facilitates hepatic metastasis of B16F1 mouse melanoma
      cells: participation of increased VCAM-1 expression in the liver.
AB  - Obstructive jaundice facilitates experimental liver metastasis in the rat model,
      but the detailed mechanisms of this facilitation remain unclear. This study aimed
      to evaluate the contribution of vascular cell adhesive molecules-1 (VCAM-1) to
      augmented hepatic metastasis in cases of obstructive jaundice. Obstructive
      jaundice was induced in male C57BL/6 mice by common bile duct obstruction for 5
      days using a Surgiclip. For the biliary decompression, obstructive jaundice was
      induced for 5 days, followed by removal of the Surgiclip. Liver specimens and
      blood samples were obtained from animals 5 days after biliary obstruction (OJ5)
      or sham operation and 2, 5, 11, 14 days after biliary decompression. The
      expression of VCAM-1 mRNA was increased in the livers from the OJ5 group. Western
      blot analysis demonstrated increased expression of VCAM-1 protein in the livers
      of the OJ5 group, in contrast with low VCAM-1 expression in the sham group. The
      expression of VCAM-1 protein was sustained at high levels at 2 days and decreased
      at 5 days after biliary decompression (BD5). For the induction of experimental
      hepatic metastasis, male C57BL/6 mice were randomized to three groups (sham, OJ5,
      BD5) of six animals each. B16F1 melanoma cells were introduced into the animals
      by an intraportal injection. Metastatic colonies in the livers were investigated
      13 days after inoculation. The mean number of metastatic colonies was
      significantly increased in the OJ5 group (70.5+/-51.2) compared to that of the
      sham group (7.2+/-7.9) (p<0.05). This augmentation of hepatic metastasis was
      abrogated in the BD5 group (16.8+/-20.3). In conclusion, our results suggest that
      augmented hepatic metastasis in cases of obstructive jaundice are partly mediated
      through VCAM-1/VLA-4 interaction.

PMID- 11295084
TI  - Oncoprotein changes in the flat lesions with atypia and invasive neoplasms of the
      urinary bladder.
AB  - We analyzed six cystectomized specimens diagnosed as transitional cell carcinoma
      by immunohistochemical evaluation to determine the presence of c-erbB2,
      transforming growth factor-alpha (TGF-alpha), c-myc, c-fos, and c-fms.
      Representative sections of flat lesions with atypia (e.g., reactive atypia,
      dysplasia, and carcinoma in situ) and invasive neoplasms (transitional cell
      carcinoma, TCC) were selected for each cystectomy specimen according to the new
      WHO/ISUP classification. The average percentage of cells found positive for c
      erbB2 were 16.3%, 45.5%, 46.1% and 67.7% in the reactive atypia, dysplasia,
      carcinoma in situ, and invasive TCC, respectively. The average percentage of
      cells found positive for TGF-alpha were 9.7%, 13.3%, 13.5%, 30.3%, respectively.
      The cells were negative for the oncoproteins c-myc and c-fos. The average
      percentage of cells found positive for the oncoprotein c-fms was 10.6%, 15.5%,
      16.7%, and 45.5% respectively. The results of this study indicated that various
      oncoproteins are expressed differently. c-erbB2, TGF-alpha and c-fms expression
      was gradually increased during tumorous progression of the urothelium from
      reactive atypia to invasive carcinoma. The presence of c-erbB2, TGF-alpha and c
      fms is an important marker for detection of an early precursor lesions of
      invasive carcinoma. However, c-myc and c-fos were not expressed in the urothelial
      reactive atypia and dysplasia and did not correlate with tumor progression.

PMID- 11295085
TI  - Immunohistochemical study of leukocyte infiltration and expression of hsp70 in
      esophageal squamous cell carcinoma.
AB  - It is reported that macrophages and CD4+ or CD8+ cytotoxic T cells have an
      important role in the suppression of cancer progression. The aim of this study
      was to clarify these immune responses in patients with esophageal cancer. We
      enrolled 28 patients with pT2 esophageal cancer that had been resected without
      preoperative adjuvant therapy. The correlations between the numbers of
      infiltrating CD4+, CD8+ and CD68+ cells, the expression of heat shock protein 70
      (hsp70) and a variety of clinicopathologic factors were analyzed. The numbers of
      CD8+ T cells and CD68+ macrophages showed a significant positive correlation with
      tumor diameter (p = 0.01, p = 0.037) and the expression of hsp70 (p = 0.01, p =
      0.02) and a negative correlation with lymph node metastasis (p = 0.0079, p <
      0.0001). The expression of hsp70 exhibited a negative correlation with lymph node
      metastasis (p = 0.023). CD8+ T cells and CD68+ macrophages might have a
      suppressive function against esophageal cancer progression. Our results suggested
      that hsp70 might play an important role in the presentation of tumor specific
      antigens.

PMID- 11295086
TI  - Immunohistochemical investigation of S100A9 expression in pulmonary
      adenocarcinoma: S100A9 expression is associated with tumor differentiation.
AB  - S100 protein A9 is associated with myeloid cell differentiation and is also
      expressed in some epithelia. However, there have been few studies on S100A9 in
      specific types of carcinomas, except for squamous cell carcinoma (SCC) because
      the expression in normal epithelia is limited to squamous epithelia. Recently,
      S100A9 gene expression has been detected in cultured human adenocarcinoma (AC)
      cells derived from various organs. In this study, we also detected S100A9 gene
      expression in human pulmonary AC cell lines by reverse transcription-polymerase
      chain reaction. Furthermore, using the monoclonal antibody against S100A9, we
      carried out an immunohistochemical evaluation of S100A9 protein expression in 70
      cases of resected pulmonary AC and examined the relation of S100A9 expression to
      tumor differentiation. S100A9 immunopositivity was 0/21 (0%) in well
      differentiated ACs, 12/30 (40%) in moderately differentiated ACs and 19/19 (100%)
      in poorly differentiated ACs, and the poorly differentiated ACs showed a
      significantly greater positive reaction. The immunopositivity in the moderately
      differentiated ACs was marked in specific cytologic subtypes. In the controls,
      conspicuous S100A9 immunopositivity was observed in pulmonary SCCs, regardless of
      the degree of differentiation, but not in adenomatous hyperplasia or normal
      surface epithelia. These above results suggest that the S100A9 protein is also
      expressed in pulmonary AC and that the expression rate in pulmonary AC shows
      higher correlation in poorly differentiated carcinomas, in agreement with our
      recent results regarding liver carcinoma. We believe S100A9 is also closely
      related to the differentiation of carcinomas of glandular cell origin.

PMID- 11295087
TI  - A phase II trial of mitomycin C, 5'-deoxy-5-fluorouridine, etoposide and
      medroxyprogesterone acetate (McVD-MPA) as a salvage chemotherapy to anthracycline
      resistant tumor in relapsed breast cancer and its mechanism(s) of antitumor
      action.
AB  - To assess the therapeutic efficacy in the combination of mitomycin C (MMC), 5'
      deoxy-5-fluorouridine (5'-DFUR), etoposide (VP-16) and medroxyprogesterone
      acetate (MPA) (McVD-MPA) to anthracycline-resistant tumor as a salvage
      chemotherapy, a phase II trial was conducted in patients with relapsed breast
      cancer. Fifty-five patients were enrolled in this trial and 54 were assessable,
      who had all previously been treated with an anthracycline regimen. The treatment
      schedule was designed with the intravenous administration of MMC (6 mg/m2) on day
      1 followed by peroral administration of VP-16 (75 mg/m2) on day 2, 4, 6 and the
      peroral administration of 5'-DFUR (600 mg/m2) and MPA (400 mg/m2) on day 1
      through 21 in one cycle. The overall tumor response rate was 40.7% (22/54)
      including 16.6% (9 cases) in complete response and 24.0% (13 cases) in partial
      response, and the long no change (NC) was observed in 18.5% (10/54) out of 44.4%
      (24/54) in NC. Of the patients with primary resistance to anthracycline 30.0%
      responded to McVD-MPA therapy. Bone and liver metastases responded in 50.0% and
      50.0%, whereas soft tissue and lung metastases responded in 36.8% and 35.2%,
      respectively. The mean time to response and response duration were 2.7 and 15.6
      months, respectively. The overall survival of the patient treated with the McVD
      MPA was superior to the non-treatment of second line therapy, and the median
      survival between McVD-MPA and non-treatment was 86 days and 50 days,
      respectively. The major adverse effect was observed in hematological toxicity
      (31.7%) such as leukopenia and thrombocytopenia and non-hematological toxicity of
      gastrointestinal events (31.7%), the toxicity was less than grade 2, and was
      tolerable during the treatment. In the experiment of MDA-MB-231 breast cancer
      cell line that was overexpressed with P-glycoprotein (P-gp) and multidrug
      resistance associated protein (MRP), the mechanism(s) by which McVD-MPA induces
      the antitumor effect to anthracycline-resistant tumor may be explained at least
      in part as follows: i) The treatment of MMC suppressed the expression of P-gp and
      MRP in a dose-and time-dependent manner, connecting the increase of the
      intracellular concentration of VP-16; ii) The treatment of MMC enhanced the
      expression of thymidine phosphorylase to increase the production of 5-FU from 5'
      DFUR in the antiangiogenic effect of MPA. These results indicate that the
      combination chemotherapy of the McVD-MPA may be an effective regimen to
      anthracycline-resistant tumor as a salvage chemotherapy to prolong the survival
      in the patient with relapsed breast cancer.

PMID- 11295088
TI  - Pharmacokinetics of intraoperative intrapleural cisplatin chemotherapy of various
      osmolarities in cases of esophageal cancer.
AB  - Intraoperative intrapleural (i.pl.) cisplatin (CDDP) treatment during thoracotomy
      was performed for esophageal cancers. Three patients underwent isotonic (308
      mOsm/l) CDDP treatment. Hypotonic CDDP treatments with a 154 mOsm/l solution and
      a 62 mOsm/l solution were administered to 4 and 9 patients, respectively. The
      maximum concentrations (Cmax) of both total and filterable platinum in the plasma
      after injection of the hypotonic solution were significantly higher than those
      after injection of the isotonic solution. The area under the curve of
      concentration versus time (AUC) of the plasma of the 62 mOsm/l solution was
      significantly higher than that of the 154 mOsm/l and isotonic solution. Although
      higher levels of the Cmax may increase side-effects, the hypotonic condition of
      the i.pl. fluid and increased AUC in the plasma may escalate the accumulation of
      platinum in i.pl. cancer cells. These results suggest that hypotonic i.pl. CDDP
      is tolerable and may be useful for treatment of the incipient phase of pleural
      carcinomatosis and for prophylaxis of postoperative recurrence.

PMID- 11295089
TI  - Doxorubicin cardiotoxicity in children: reduced incidence of cardiac dysfunction
      associated with continuous-infusion schedules.
AB  - We retrospectively reviewed the medical records of 97 children (59 boys and 38
      girls) with a median age of 13 +/- 4 years who had been treated with continuous
      infusion of doxorubicin at a dosage of 60 mg/m2 over 24 h (61 patients) or at a
      dosage of 75 mg/m2 over 72 h (36 patients). The drug was administered every 3
      weeks. The cardiac status of patients was evaluated as a baseline and every 6
      months during, and following therapy (median, 30.5 months). The evaluations
      included M-mode and two-dimensional echocardiography. Congestive heart failure
      developed in only one patient in this series, an 8-year-old girl who ultimately
      died of her cardiac complication. This incidence of doxorubicin-induced
      cardiotoxicity was compared with that seen in a control group of pediatric
      patients previously treated with doxorubicin at similar dosages but with a rapid
      infusion. The result compared favorably to the 13% incidence of cardiotoxicity (p
      = 0.03) and 7% mortality (p < 0.01) in the control group. No changes in the
      levels of tumor response were noted in children treated by continuous infusion
      when compared with historical controls. Continuous-infusion schedules of
      doxorubicin thus result in fewer incidences of cardiotoxicity in children and
      should be considered for wider application in pediatric cancer patients receiving
      doxorubicin.

PMID- 11295090
TI  - Mitochondrial genotypes and radiation-induced micronucleus formation in human
      osteosarcoma cells in vitro.
AB  - We investigated whether or not the mitochondrial genotypes affect radiation
      induced micronucleus (MN) formation. For that purpose, the rho+, KT1 and rho0
      human osteosarcoma cell lines were used, which carry the wild-type mitochondrial
      DNA (mtDNA), the tRNALys mutant mtDNA and no mtDNA, respectively. Despite no
      significant difference in the clonogenic radiosensitivity, the rho+, KT1 and rho0
      cells exhibited high, intermediate and low radiosensitivities, respectively, to
      the MN induction in cytokinesis-blocked binucleated cells. Such differential MN
      inductions were correlated with high, intermediate and low levels of cellular ATP
      in the rho+, KT1 and rho0 cells, respectively, but not exactly with ROS
      production. Antimycin A that inhibits the respiratory complex III reduced the
      rate of radiation-induced MN induction in the rho+ and KT1, but not rho0 cells.
      Thus, the functional status of the mtDNA to produce ATP appears to play a
      significant role for radiation-induced MN.

PMID- 11295091
TI  - Dihydropyrimidine dehydrogenase activity of cancerous and non-cancerous tissues
      in liver and large intestine.
AB  - 5-fluorouracil (5-FU) is a widely used chemotherapeutic agent for various
      carcinomas. However, the therapeutic effect of 5-FU differs among patients. The
      differences in the effectiveness of 5-FU are thought to be based on the different
      enzymatic activity which inactivates 5-FU of the host tissue. 5-FU is catabolized
      to 2-fluoro-beta-alanine by dihydropyrimidine dehydrogenase (DPD) in liver and
      tumors. In this study, we investigated the clinical significance of detecting DPD
      activity in patients with hepatocellular and colorectal carcinomas. DPD activity
      in 63 hepatocellular carcinomas (HCCs), 3 cholangiocellular carcinomas (CCCs), 63
      non-cancerous liver tissues adjacent to HCCs (N-HCCs), 6 normal livers (NLs), 189
      colorectal carcinomas (CRCs), and 189 non-cancerous colorectal mucosas (N-CRCs)
      was analyzed by enzyme-linked immunosorbent assay (ELISA). The mean DPD
      activities of these tissues were 209 +/- 187 Unit (U)/mg protein (HCC), 140 +/-
      34 (CCC), 105 +/- 50 (N-HCC), 93 +/- 24 (NL), 58 +/- 45 (CRC), and 83 +/- 92 (N
      CRC). DPD activity of HCC was higher than that of CRC (p < 0.0001). DPD activity
      of N-HCC was higher than that of N-CRC (p < 0.0001). DPD activity of HCC was
      higher than that of N-HCC (p = 0.0014), on the other hand, DPD activity of CRC
      was lower than that of N-CRC (p < 0.0001). Tumor DPD activity in HCC and CRC did
      not correlate with tumor differentiation or progression nor with patient
      survival. In 20 CRC patients with synchronous liver metastasis, who underwent
      post-operative 5-FU chemotherapy through the hepatic artery, the mean survival
      time (29 months) of 9 patients with high DPD was not significantly different from
      that of 11 patients with low DPD (18 months, p = 0.3412). These findings could
      provide an explanation for the relative 5-FU resistance of HCC compared with CRC.
      However, the DPD activities of tumors may not reveal tumor differentiation or
      progression in HCCs or in CRCs. Moreover, the DPD activity of primary CRC may not
      be a good indicator of the 5-FU chemosensitivity of synchronous liver metastasis.

PMID- 11295092
TI  - Further evidence that altered p16/CDKN2 gene expression is associated with lymph
      node metastasis in squamous cell carcinoma of the esophagus.
AB  - Esophageal squamous cell carcinoma (ESCC) has high malignant potential with a
      poor outcome. Lymph node metastasis is the most useful indicator for predicting
      the outcome of ESCC. The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene
      cooperatively regulate CDK4-mediated phosphorylation of RB protein in the cell
      cycle. We immunohistochemically detected p16, cyclin D1, and RB expressions in
      both primary lesions and metastatic lymph nodes in ESCC. Among the 50 ESCC
      primary lesions, 24 (48%) were positive for p16, while 26 (52%) were negative for
      p16. Sixteen (32%) were p16-positive, 34 (68%) were p16-negative among the 50
      ESCC metastatic lymph nodes. Eight cases (16%) were p16-positive in primary
      lesion and p16-negative in lymph node, however, no cases that was p16-negative in
      the primary tumor exhibited p16-positivity in metastatic lymph nodes (p <
      0.0001). Seventeen (34%) of the 50 ESCC primary lesions were cyclin D1-positive,
      while 33 (66%) were cyclin D1-negative. Twenty-four (48%) were cyclin D1
      positive, 26 (52%) were cyclin D1-negative among the 50 metastatic lymph nodes.
      Five cases (10%) were cyclin D1-positive in primary lesion and cyclin D1-negative
      in lymph node, and 12 cases (24%) were cyclin D1-negative in primary lesion and
      cyclin D1-positive in lymph nodes. Nine cases (18%) were RB-negative in 50
      primary lesions, and the rate of loss of RB expression in metastatic lymph nodes
      was not markedly higher than in primary lesions. Thirty-nine (78%) of 50 primary
      lesions and 46 (92%) of 50 metastatic lymph nodes had altered expression of at
      least one of the three G1 control genes. Tumor cell with disruption of these cell
      cycle regulators can get a growth advantage and metastatic potential during tumor
      progression, especially p16/CDKN2 alterations may be associated with lymph node
      metastasis in ESCC. These results also suggest that tumor cells in metastatic
      lymph nodes may have more aggressive proliferation and higher malignant potential
      than tumor cells in primary lesions.

PMID- 11295093
TI  - Reduction in the incidence of Helicobacter pylori-associated carcinoma in
      Japanese young adults.
AB  - Helicobacter pylori (Hp) is a major risk factor for gastric carcinogenesis. In
      Japan, the incidence of Hp infection in young adults has declined markedly. The
      purpose of this study was to clarify this trend in the incidence of Hp-associated
      gastric carcinoma (GCa) in young (under 30 years of age) Japanese patients. We
      enrolled 53 such patients who underwent surgical resection of GCa in one of 18
      hospitals in the Hiroshima prefecture between 1976 and 1999. The patients were
      classified into groups based on three 8-year periods (1976-83, 1984-91, and 1992
      1999) in which their cases occurred. We compared the numbers of patients and
      estimated the histology of carcinomas, grades of gastritis and Hp infection
      histologically. Of the 53 patients, 49 (92%) showed Hp infection. The frequency
      of GCa in young adults has decreased gradually (21, 18, and 14 patients in 1976
      83, 1984-91 and 1992-99, respectively). The numbers of Hp-positive carcinomas
      decreased radically (21, 17 and 11 patients, respectively). This trend was
      associated with improvement in the degree of gastritis in non-neoplastic mucosa.
      Of the four Hp-negative patients, three had signet ring cell carcinoma. Moreover,
      the numbers of patients with non-signet ring cell carcinoma also decreased (18,
      12 and 7 patients in each period, respectively). These results suggest that Hp
      associated carcinoma has declined gradually in young Japanese.

PMID- 11295094
TI  - Wild-type p53 gene transfection in human cultured sarcomas: effect of CDDP.
AB  - We examined the susceptibility of five human bone and soft tissue sarcoma cell
      lines to transfection with recombinant p53 adenovirus vector (AxCA-p53).
      Transfection efficiency was more than 90% at 72 h with AxCA-lacZ at a
      multiplicity of infection (MOI) of 50 in all the cell lines, except for MG-63
      (p53 gene mutated) cells. Western blot analysis showed overexpression of both
      P21/Waf1 and Bax protein in all the cell lines, implying sufficient and
      successful p53 gene transfection. AxCA-p53 transfection at MOI of 50 resulted in
      a significant decline of viable cells at 72 h, due to apoptosis, in NY (mutated)
      and Saos-2 (deletion), but not in the other three lines. The two apoptosis
      induced cell lines showed a gradual increase in Bax expression up to 72 h and non
      detectable expression of Bcl-XL from 48 h, suggesting the involvement of an
      apoptosis-inducing mechanism. Pre-treatment with cis-diamminedichloroplatinum
      (II) (CDDP) at 0.1 microg/ml significantly suppressed tumor cell viability in NY
      and HuO-3N1 (mutated), but not in the other three lines including HT-1080
      carrying the wild-type p53 gene, implying the existence of different mechanisms
      for the tumor suppressive effect of p53 gene transfection and CDDP. These results
      indicate that wild-type p53 gene transfection with CDDP is a promising therapy
      for some, but not all, non-resectable bone-and soft tissue sarcomas, regardless
      of intrinsic p53 gene status.

PMID- 11295095
TI  - A new bisphosphonate treatment option for giant cell tumors.
AB  - Treatment of giant cell tumors (GCT) especially in the vertebrae remains
      controversial. With multidisciplinary treatments, their results are still
      insufficient. Moreover, GCT shows the potential for malignant transformation and
      metastasis, additional options such as adjuvant medication must be considered. We
      report favorable results in three consecutive cases diagnosed with GCT of the
      spine which were treated with radiotherapy and bisphosphonate (BP) as a new
      treatment option, and present a review of the literature and a comparison with
      these case reports.

PMID- 11295096
TI  - Dysregulation of telomerase activity and expression in lymphokine-activated
      killer cells from advanced cancer patients: possible involvement in cancer
      associated immunosuppression mechanism.
AB  - There exists cancer-associated immunosuppression, and the generation of
      lymphokine-activated killer (LAK) cells is impaired in patients with advanced
      cancer. Telomerase has been reported to be upregulated in the activation of
      lymphocytes to proliferate against immune stimulation as well as in the malignant
      transformation of immortal cancer cells. We attempted to clarify the involvement
      of telomerase in the impairment of LAK cell generation in patients with advanced
      cancer. LAK cells were generated by stimulation with interleukin (IL)-2 and
      immobilized anti-CD3 antibody (IL-2/CD3 system) from peripheral blood mononuclear
      cells of healthy volunteers (he-LAK) or patients with advanced cancer (ca-LAK),
      and proliferative potential of LAK cells was evaluated on the basis of population
      doubling level (PDL). Telomere length and telomerase activity of LAK cells were
      measured by the hybridization with oligonucleotide (TTAGGG)4 and by the telomeric
      repeat amplification protocol (TRAP) assay, respectively. Effects on telomerase
      activity in LAK cells of serum from cancer patients, transforming growth factor
      (TGF)-beta, and IL-10 were also examined. The lifespan of ca-LAK (15.2 +/- 5.1
      PDLs) was significantly shorter than that of he-LAK (22.6 +/- 8.3 PDLs) (p =
      0.0358). There were no significant differences between he- and ca-LAK in telomere
      length before IL-2/CD3 stimulation and maximal telomerase activity induced. The
      telomerase activity induced in ca-LAK failed to elongate sufficiently the
      telomeric ends (-35.2 +/- 46.2 bp) compared with that in he-LAK (16.8 +/- 41.5
      bp) (p = 0.0448). The telomerase activity was initially detectable on day 2 in
      all he-LAK, whereas 8 (61.5%) of 13 ca-LAK expressed telomerase activity on day 3
      or later following the stimulation, showing a significant retardation of
      telomerase expression (p = 0.0116). The addition to the LAK cell generation
      system of serum from cancer patients, as well as IL-10, but not transforming
      growth factor (TGF)-beta, suppressed the telomerase activity. This serum-induced
      suppression of telomerase activity in LAK cells was abrogated with the addition
      of anti-IL-10 antibody but not with anti-TGF-beta antibody. It is suggested that
      the dysregulation of telomerase activity and expression exists in LAK cells of
      cancer patients, resulting in the impairment of LAK cell generation in patients
      with advanced cancer. Serum IL-10 may be involved in the impairment of LAK cell
      generation by the suppression of telomerase activity of lymphocytes in vivo.
      Thus, the dysregulation mechanism of telomerase activity and expression in
      lymphocytes of cancer patients may be attributable, in part, to cancer-associated
      immunosuppression.

PMID- 11295097
TI  - Inverse association of non-steroidal anti-inflammatory drugs and malignant
      melanoma among women.
AB  - Recent human epidemiologic studies suggest that non-steroidal anti-inflammatory
      drugs (NSAIDs) have preventive effects against cancers of the colon, breast, and
      prostate. Laboratory and animal studies also provide evidence of antineoplastic
      effects of NSAIDs against a variety of solid tumors, including skin cancer. We
      studied the effects of NSAIDs on malignant melanoma in women utilizing a case
      control experimental design involving 110 women with histologically proven
      malignant melanoma, and 609 female controls frequency matched to the cases on
      age, and place of residence. We observed a significant decrease in the relative
      risk (RR) of malignant melanoma with regular intake of common over the counter
      NSAIDs such as aspirin and ibuprofen (RR = 0.45, 95% CI = 0.22-0.92, p < 0.05).
      Adjustment for sun exposure did not change the magnitude of the estimate. Our
      results are the first to show that NSAIDs may have value in the chemoprevention
      of malignant melanoma.

PMID- 11295098
TI  - Breast cancer during the HIV epidemic in an African population.
AB  - Both human immunodeficiency virus (HIV) infection and certain malignancies
      including breast cancer occur predominantly in premenopausal women in an African
      population. Cancers that are associated with HIV infection are Kaposi's sarcoma
      (KS), non-Hodgkin's lymphoma (NHL) and invasive cervical carcinoma. Recently,
      cases of breast cancer have been reported in patients with HIV infection but an
      association between breast cancer and HIV infection has yet to be determined. The
      present study investigated for association between HIV infection and breast
      cancer. Among the 101 patients studied, 50 were cases with breast cancer while
      the remaining 51 were referents with conditions other than mammary cancer.
      Patients with breast cancer 30 years of age and below recorded in the Cancer
      registry during 1974-1987 constituted 8% while those recorded during the ongoing
      AIDS epidemic amounted to only 2%. When a similar comparison was undertaken among
      patients below 50 years there was also an overall decrease in the proportion of
      patients from 76.1 to 58.0%. Conversely, in the age groups above 50 years the
      breast cancer cases increased from 33.9 to 42% respectively (chi2=1.83 on 1df,
      p=0.18). The overall prevalence of HIV infection among the control group was
      35.5% (95% CI=22.2-48.4) while among breast cancer patients it was 6% (95% CI=0.6
      12.6). Women below 50 years of age with breast cancer were less likely to be HIV
      positive; OR=0.18: (95% CI=0.04-0.76) chi2=5.95; p=0.01. However, there is no
      basis to suggest that HIV infection is protective against this malignancy. AIDS
      associated mortality commonly occurs in the second and third decades of life and
      probably these deaths have changed the demographic of the disease in an African
      population. The impact of AIDS associated mortality on cancer registries needs
      attention.

PMID- 11295099
TI  - Regulation of BRCA1 and BRCA2 transcript in response to cisplatin, adriamycin,
      taxol and ionising radiation is correlated to p53 functional status in ovarian
      cancer cell lines.
AB  - Recent studies suggest that BRCA1 and BRCA2 expression, in response to cytotoxic
      agents, may be dependent on p53 status. To investigate this possibility, we
      quantified their transcripts in ovarian cancer cells, PA1 (wild-type p53), CaOV-3
      (mutated p53) and SKOV-3 (null p53) exposed to four cytotoxic agents. In PA1,
      taxol and cisplatin had no effect, while adriamycin and ionising radiation (IR)
      induced both genes. In SKOV-3, expression decreased in response to taxol and
      cisplatin, and initially decreased then increased in response to adriamycin while
      IR had no effect. CaOV-3 responded similarly to SKOV-3, except for both genes
      being increased by cisplatin. We speculate that this regulation may be part of
      the survival response to certain cytotoxic agents and may be dependent in part on
      p53 status of cells.

PMID- 11295100
TI  - Fetal fibronectin: a new screening-marker for bladder cancer?
AB  - Early detection of transitional cell carcinoma (TCC) of the urinary bladder is
      essential for effective treatment. While several serum markers have been
      evaluated, none have been widely accepted for practical clinical use. Thus,
      urinary markers have been introduced and investigated to detect the evidence of
      bladder cancer. But sensitivity and specificity range around 80% respectively. In
      a prospective study we evaluated fetal fibronectin in the urine of patients with
      TCC of the urinary bladder. The positivity of oncofetal fibronectin was measured
      in morning urine samples by membrane immunoassay. This FFN membrane immunoassay
      is a qualitative test, a solid-phase immunogold assay. A positive sample will
      result in a single spot after binding of the oncofetal fibronectin-immunogold
      complex to the membrane containing a monoclonal antibody specific to oncofetal
      fibronectin (FDC-6, which specifically recognizes III-CS region). The morning
      urine samples were collected from patients with TCC before they underwent
      transurethral resection (n=40, 34 non-invasive and 6 invasive carcinomas) and
      healthy controls (n=20). Oncofetal fibronectin was investigated in the surgical
      samples by immunohistochemistry (antibody FDC-6, APAAP technique). We found a
      positive result for oncofetal fibronectin in 38/40 patients with transitional
      cell carcinoma of the urinary bladder. Two patients with a small pTaG1-TCC showed
      negative results. In the urine of healthy controls no positive results were
      detected. Thus, there is a sensitivity of 95% and a specificity of 100%. The TCC
      was demonstrated as a source of oncfn. To our knowledge this is the first study
      showing that patients with an evident TCC have a demonstrable amount of oncofetal
      fibronectin in the urine. We conclude that a positive result is common in TCC
      patients. The sensitivity and specificity of this test seems to be
      extraordinarily high. Because of the small number of cases further studies are
      required.

PMID- 11295101
TI  - Prolongation of survival of rats injected with hepatoma cells treated by nuclei
      extracts from mouse and rat embryo cells.
AB  - Cancer cells express particular genes, part of which are normally active during
      the embryonic development. On the other hand, young embryos are able to
      differentiate teratocarcinoma or leukemia cells, likely by producing
      differentiation factors. In this work, rat and mouse embryo cell nuclei extracts
      were tested on hepatoma carcinoma cells LFCl2A: they inhibit the cell growth in
      culture and increase the survival of syngeneic rats injected with hepatoma cells
      incubated with these extracts. This inhibition is correlated with a decrease of
      DNA synthesis without toxic effect: It seems to be due to the mixture of tight
      binding DNA proteins, possibly transcriptional factors.

PMID- 11295102
TI  - Quinoxaline 1,4-dioxides as anticancer and hypoxia-selective drugs.
AB  - Hypoxic cells which are found in solid tumors are resistant to anticancer drugs
      and radiation therapy. Thus, for effective anticancer chemotherapy, it is
      important to identify drugs with selective toxicity towards hypoxic cells.
      Quinoxaline 1,4-dioxides (QdNOs) are heterocyclic aromatic N-oxides that have
      been found to possess potent antibacterial activities (inhibit microbial DNA
      synthesis) especially under anaerobic conditions; thus they are under evaluation
      as bioreductive drugs for the treatment of solid tumors (1). We investigated the
      ability of four differently substituted QdNOs to inhibit cell growth and induce
      cell cycle changes in two human tumorigenic epithelial cell lines under oxic
      conditions. We also evaluated the toxicity of these drugs to cancer cells
      cultured under hypoxic conditions. Two epithelial cell lines (the T-84 human
      colon cancer-derived cell line, and the SP-1 keratinocyte cell line) were treated
      with various doses of the QdNOs and harvested at different times after treatment.
      Proliferation and cell cycle results showed a structure-function relationship in
      the activity of the various QdNO compounds with the 2-benzoyl-3-phenyl-6,7
      dichloro-derivative of QdNO (DCBPQ) being the most potent cytotoxin and hypoxia
      selective drug. The 2-benzoyl-3-phenyl (BPQ) and the 2-acyl-3-methyl-derivative
      of QdNO (AMQ) were less cytotoxic but arrested almost 50% of the cells in the G2M
      phase of the cell cycle at doses of 30 and 120 microM, respectively. The
      tetramethylene derivative of QdNO (TMQ) did not affect the growth and cycling of
      cells cultured in air and was the least potent cytotoxin to hypoxic cells. Our
      results indicate that the QdNOs are hypoxia-cytotoxic drugs whose activity varies
      according to the substituents on the quinoxaline 1,4-dioxide heterocycle. Because
      of their selective toxicity to hypoxic cells (cells found in human tumors), these
      drugs may provide useful therapeutic agents against solid tumors.

PMID- 11295104
TI  - Detection of messenger RNA in leukocytes or plasma of patients with chronic
      myeloid leukemia.
AB  - We investigated the presence of free mRNA in the plasma of patients with chronic
      myeloid leukemia (CML), through RT-PCR analysis of G3PDH, a metabolism gene. We
      also analysed the presence of mRNA for HLM, a human oxysterol-binding protein
      homologue recently described as a potential marker for blood dissemination of
      solid tumors. Our results showed the presence of metabolism G3PDH mRNA in the
      plasma of 5/11 (45%) CML patients studied but HLM mRNA was not detected in any of
      the plasma studied. HLM mRNA was detected in the leukocytes of 4/5 (80%) CML
      patients. This work reports for the first time free mRNA in the plasma of CML
      patients. Our results also suggest that the detection of HLM could be a potential
      molecular marker for the follow-up in hematological malignancies.

PMID- 11295103
TI  - Relation of prenephrectomy CD profiles and serum cytokines to the disease outcome
      and response to IFN-alpha/IL-2 therapy in renal cell carcinoma patients.
AB  - Immune parameters, including cytokine levels and CD profiles were determined in
      78 renal cell carcinoma patients (RCC) prior to nephrectomy. The values were
      correlated with the outcome of disease and response to cytokine-based treatment
      during a 3-year follow-up. Significantly lower frequency of progressions and
      higher proportion of survivors were recorded in 24 treated patients compared to
      43 untreated ones (22.9% vs. 53.5% and 82.9% vs. 55.8%) illustrating the
      beneficial effect of immunotherapy on the course of RCC at localized stage. RCC
      related immune changes are demonstrated by reduced proportion of CD19+, CD28+,
      HLA-DR+, CD19+/80+ and CD8+/28+ subsets, by increased serum levels of IL-6, sIL
      2R, CRP and by impaired production of IL-2 and TNF-alpha released by in vitro
      stimulated PBMC. Only increased CRP, IL-6 serum values, decreased CD8+ and
      increased CD122+ were significantly related to patients' prognosis. Comparisons
      of preoperative CD profiles and cytokine values with the response to IL-2/IFN
      alpha based therapy disclosed significant correlation in only CD80+ and CD19+/80+
      subsets. Treated patients who relapsed during the 3-year follow-up exhibited at
      the diagnosis significantly reduced proportion of CD80+ and CD19+/80+ cells
      (CD80+ means - 0.79 vs. 1.69 and CD19+/80+ means - 0.32 vs. 0.61) comparing to
      those surviving disease-free. In addition initial proportion of CD3+, CD8+ and
      CD19+ cells was reduced in treated patients who manifested progression but
      statistical difference from those remaining disease-free was not proved.

PMID- 11295105
TI  - An individual patient data meta-analysis of long supported adjuvant chemotherapy
      with oral carmofur in patients with curatively resected colorectal cancer.
AB  - To reappraise the benefits of the long supported chemotherapy with carmofur, a
      meta-analysis based on individual patient data from the three clinical trials was
      performed by pooling 614 patients from three trials, there is a statistically
      significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit
      (2p=0.021) for carmofur; and a highly significant advantage for carmofur in DFS
      (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta
      analysis strongly suggested an effect of oral carmofur in a long supported
      chemotherapy for curatively resected colorectal carcinoma.

PMID- 11295106
TI  - Neuronal cell death in nervous system development, disease, and injury (Review).
AB  - Neuronal death is normal during nervous system development but is abnormal in
      brain and spinal cord disease and injury. Apoptosis and necrosis are types of
      cell death. They are generally considered to be distinct forms of cell death. The
      re-emergence of apoptosis may contribute to the neuronal degeneration in chronic
      neurodegenerative disease, such as amyotrophic lateral sclerosis and Alzheimer's
      disease, and in neurological injury such as cerebral ischemia and trauma. There
      is also mounting evidence supporting an apoptosis-necrosis cell death continuum.
      In this continuum, neuronal death can result from varying contributions of
      coexisting apoptotic and necrotic mechanisms; thus, some of the distinctions
      between apoptosis and necrosis are becoming blurred. Cell culture and animal
      model systems are revealing the mechanisms of cell death. Necrosis can result
      from acute oxidative stress. Apoptosis can be induced by cell surface receptor
      engagement, growth factor withdrawal, and DNA damage. Several families of
      proteins and specific biochemical signal-transduction pathways regulate cell
      death. Cell death signaling can involve plasma membrane death receptors,
      mitochondrial death proteins, proteases, kinases, and transcription factors.
      Players in the cell death and cell survival orchestra include Fas receptor, Bcl-2
      and Bax (and their homologues), cytochrome c, caspases, p53, and extracellular
      signal-regulated protein kinases. Some forms of cell death require gene
      activation, RNA synthesis, and protein synthesis, whereas others forms are
      transcriptionally-translationally-independent and are driven by posttranslational
      mechanisms such as protein phosphorylation and protein translocation. A better
      understanding of the molecular mechanisms of neuronal cell death in nervous
      system development, injury and disease can lead to new therapeutic approaches for
      the prevention of neurodegeneration and neurological disabilities and will expand
      the field of cell death biology.

PMID- 11295107
TI  - A combination analysis of p53 and p21 in gastric carcinoma as a strong indicator
      for prognosis.
AB  - We studied p53 and p21 expression simultaneously in gastric carcinoma tissues to
      investigate the clinical significance of p53-p21 pathway in this disease. One
      hundred sixty-four primary gastric carcinoma specimens were immunohistochemically
      stained for p53 and p21 protein, and clinicopathological features of the cases
      were examined. P53 was stained negatively, while p21 was stained positively in
      each normal stomach epithelium. P53, and p21 positive staining was observed in 82
      (50%) and 61 (37.2%) tumors, respectively. Unexpectingly, no correlation was
      found between p53 and p21 staining status. Tumors demonstrating preserved p53-p21
      pathway [p53(-)/p21(+)], observed in 20.1% of the tumors, displayed less
      aggressive characteristics, and no recurrent disease after curative resection.
      While tumors demonstrating disrupted p53-p21 pathway [p53(+)/p21(-)], observed in
      32.9% of the tumors, displayed significantly more aggressive characteristics,
      poorer survival and higher recurrence rate than the tumors demonstrating other
      staining patterns. P53-p21 pathway was widely altered in gastric carcinomas. The
      combined evaluation of p53 and p21 expression in gastric carcinoma tissues is
      suggested to have clinical importance by indicating not only the malignant
      potential of each tumor, but also the prognosis of this disease.

PMID- 11295108
TI  - Sesaminol from sesame seed induces apoptosis in human lymphoid leukemia Molt 4B
      cells.
AB  - The exposure of human lymphoid leukemia Molt 4B cells to sesaminol, a component
      of sesame oil led to both growth inhibition and the induction of apoptosis.
      Morphological change showing apoptotic bodies was observed in the cells treated
      with sesaminol. The fragmentation of DNA by sesaminol to oligonucleosomal-sized
      fragments that are characteristics of apoptosis was observed to be concentration-
      and time-dependent. These findings suggest that growth inhibition of Molt 4B
      cells by sesaminol results from the induction of apoptosis in the cells.

PMID- 11295109
TI  - High expression of the proliferation and apoptosis associated CSE1L/CAS gene in
      hepatitis and liver neoplasms: correlation with tumor progression.
AB  - The CSE1L/CAS protein (CAS) is a Ran-binding protein with a function as nuclear
      transport (export) factor. Like recently observed for ran and other ran-binding
      proteins, CSE1L/CAS simultaneously plays a role in the mitotic spindle
      checkpoint, which assures genomic stability during cell division. This checkpoint
      is frequently disturbed in neoplasias of various origin, including hepatic
      tumors. We have evaluated by immunohistology the expression of CAS in adult and
      embryonic liver, hepatitis, and in liver hyperplasias. Normal hepatocytes
      revealed no CAS expression while embryonic liver showed strong expression in all
      parenchymal cells. Bile ducts stained positive with anti-CAS antibodies, and
      strong CAS expression was also detected at the interface between bile ducts and
      hepatocytes under conditions associated with regenerative proliferation. The
      localization of these CAS expressing cells correlated with the distribution of
      putative liver stem-cells. In active viral (but not in inactive) hepatitis,
      strong hepatocytal CAS expression correlates in site and intensity with degree of
      inflammation. Neoplastic liver demonstrated different degrees of CAS expression:
      no remarkable expression in adenomas, moderate expression in a narrow rim of
      hepatocytes and in periseptal cholangiolar proliferations in focal nodular
      hyperplasia, and strong CAS expression in hepatocellular carcinoma. Less
      differentiated tumors stain stronger than well differentiated. Cholangio-cellular
      carcinomas show even stronger CAS expression than hepatocellular carcinomas. Our
      observation of strong expression of CAS in liver cells that are committed for
      proliferation among them possibly liver stem cells, and in liver neoplasms, is
      consistant with the fact that CAS functions not solely as a nuclear transport
      factor but that it is also essential for cell proliferation, particularly for the
      mitotic spindle checkpoint. Interestingly, genomic instability is frequently
      observed in hepatic tumors which we have shown here to express large amounts of
      CAS. Since the degree of CAS-expression correlates with the grade of tumor
      dedifferentiation, we suggest that CAS should also be further investigated as
      prognostic marker for hepatic neoplasms.

PMID- 11295110
TI  - Uptake of 1-deoxy-1-[125I]iodo-D-mannoheptulose by different cell types: in vitro
      and in vivo experiments.
AB  - D-mannoheptulose was recently proposed as a tool to label preferentially insulin
      producing cells in the pancreatic gland in the perspective of the non-invasive
      imaging of the endocrine pancreas. In such a perspective, we have now synthesized
      1-deoxy-1-[125I]iodo-D-mannoheptulose ([125I]MH) and examined its uptake by
      different rat cell types. No phosphorylation of [125I]MH by bovine heart
      hexokinase could be detected. The apparent distribution space of [125I]MH largely
      exceeded that of [U-14C]sucrose, considered as an extracellular marker, in
      erythrocytes, parotid cells, hepatocytes, pancreatic pieces and isolated
      pancreatic islets. Relative to the mean intracellular distribution space of 3HOH,
      that of [125I]MH was not significantly different in pancreatic pieces from either
      normal rats or streptozotocin-induced diabetic animals (STZ rats). In pancreatic
      islets, the uptake of [125I]MH was decreased at low temperature, but failed to be
      significantly affected by cytochalasin B. Sixty min after the intravenous
      injection of [125I]MH, the radioactive content of selected organs displayed the
      following hierarchy: muscle<pancreas<liver<parotid<kidney<plasma. In this
      respect, there was no obvious difference between control and STZ rats. Taken as a
      whole, these findings suggest that 1-deoxy-1-[125I]iodo-D-mannoheptulose does not
      display the same specificity towards GLUT2, as that previously documented in the
      case of D-[3H]- mannoheptulose.

PMID- 11295111
TI  - Chromosome 22q11 microdeletion in conotruncal heart defects: clinical
      presentation, parental origin and de novo mutations.
AB  - Using genotype analysis and multiplex quantitative polymerase chain reaction
      (PCR), chromosome 22q11 deletions were examined in 252 patients with syndromic or
      isolated conotruncal heart defect. Of these patients, 19 (7.5%) were found to be
      hemizygous for chromosome 22q11. Parental origin of the deleted chromosome was
      determined in 16 cases: one patient (6.3%) inherited a deleted chromosome 22 from
      his mother; all the others (93.7%) consisted of de novo mutations. One-third
      (5/15) of the de novo 22q11 deletions were of paternal origin and the remainder
      derived maternally. These results lend further support to our current knowledge
      of chromosome 22q11 microdeletion syndromes and their implications for the
      genetic counseling of individuals diagnosed with conotruncal heart defects.
      Possible mechanisms for gender-biased parental origin are discussed.

PMID- 11295112
TI  - Effect of aging and hypertension on beta-myosin heavy chain in heart of
      spontaneously hypertensive rats.
AB  - During aging rat myocardium undergoes structural changes characterized by a shift
      in the synthesis of myosin heavy chain (MHC) from V1 isoform, composed of two
      alpha-MHC, to V3 isoform, composed of two beta-MHC. In rat, besides ageing,
      cardiac hypertrophy as adaptive response to a superimposed pressure load (such as
      hypertension) is characterized by predominance of V3 myosin isoform. The aim of
      our study was to evaluate the expression of beta-MHC in right (RV) and left (LV)
      ventricles of spontaneously hypertensive rats (SHRs), a well defined animal model
      of hypertension, in relation to aging. We used very young (8-week old) and young
      (15-week old) SHRs and age-matched normotensive Harlan Sprague-Dawley control
      rats. By Western analysis, we found that beta-MHC is already present in both RV
      and LV of 8-week old SHRs, and is markedly predominant in RV and LV of 15-week
      old SHRs, when compared with age-matched control rats. Our study showed that the
      shift to V3 myosin isoform in SHRs is an early event, resembling accelerated
      senescence. We have also demonstrated that beta-MHC is actively synthesized also
      in young (15-week old) normal rats.

PMID- 11295113
TI  - Cell killing and mutation induction by heavy ion beams.
AB  - Carbon beam radiotherapy for cancer patients was initiated in Japan in June 1994.
      This study attempts to clarify the radiobiological effects of heavy ion beams. In
      this study, human cancer cell lines (RMG-1, MDA-MB231) and V79 cells were used.
      The cell killing was determined by colony forming assay, and mutation induction
      was determined by counting the number of 6-thioguanine resistant colonies (hprt
      locus mutation assay). The cell lines were irradiated with carbon (20 or 80
      keV/microm) or neon beams (80 keV/microm). Carbon ions with a higher LET value
      (80 keV/microm) had an enhanced cytotoxic effect compared to those with a lower
      LET value (20 keV/microm). Carbon beams produced a slightly stronger cytotoxic
      effect than neon beams when irradiated at the same LET level (80 keV/microm), but
      the difference was not remarkable. The mutant fraction was significantly higher
      in all cell lines when they were irradiated with heavy ion beams, compared to the
      results for X-ray irradiation. The mutant fraction increased when the LET of the
      carbon beams increased. At equivalent LET values, the mutant fraction was lower
      for neon beams than for carbon beams. Fractionation of carbon beam irradiation
      had no effect on survival, but reduced the mutant fraction. Neon beams might be
      more appropriate for heavy ion therapy, especially when higher doses are being
      used. In addition, the fractionation of heavy ion beam administration might be
      appropriate for reducing the mutant fraction.

PMID- 11295115
TI  - The biochemical analysis of neurotransmitters in central neurocytomas.
AB  - Central neurocytomas are rare benign intraventricular tumours composed of small
      round synaptophysin-positive cells, suggesting a neuronal origin of these tumour
      cells. Although past electron microscopic studies demonstrated synaptic vesicles
      in the synapse of central neurocytomas, the kinds of neurotransmitters in central
      neurocytomas have never been identified. In this study we analyzed
      neurotransmitters in an attempt to clarify the tumorigenesis of central
      neurocytomas. We studied frozen central neurocytoma specimens from four patients.
      The tissue levels of glutamate and GABA (gamma-aminobutyric acid) in the tumours
      were determined by gas chromatography-mass spectrometry (GC-MS) using a selected
      ion monitoring method. The tissue levels of acetylcholine, choline,
      catecholamines and metabolites of catecholamines in the tumours were measured by
      high-performance liquid chromatography combined with electrochemical detection.
      Choline was found in extremely high concentration in all central neurocytomas
      when compared with levels in controls. In one central neurocytoma, GABA was found
      in extremely high concentration compared with controls. In all central
      neurocytomas, glutamate was found in lower or identical concentrations compared
      with controls. In all central neurocytomas and controls, dopamine and
      catecholamine concentrations were extremely low. These results indicated that the
      histogenesis of central neurocytomas begins with the subependymal stem cells,
      which have the potential to differentiate into cholinergic or GABA neurons.

PMID- 11295114
TI  - Correlation between induction of the mac25 gene and anti-proliferative effects of
      1alpha,25(OH)2-D3 on breast cancer and leukemic cells.
AB  - In the differentiation of a myelomonocytic cell line U937 treated with 1alpha,25
      dihydroxyvitamin D3 [1alpha,25(OH)2-D3], transient proliferation was observed
      prior to cell growth arrest. The expression of the p21 and p27 genes increased
      transiently and decreased quickly in the proliferation, suggesting that other
      genes may contribute to the growth arrest of the cell line after reduction of the
      p21 and p27 genes. The mac25 gene was isolated as a gene associated with cellular
      senescence and growth suppression. Despite a previous report that retinoic acid
      (RA) induced the mac25 gene, the mac25 gene did not increase in U937 cells
      treated with RA but did increase in the cells treated with 1alpha,25(OH)2-D3. The
      high level of the expression of the mac25 gene was detected for four days after
      the 1alpha,25(OH)2-D3 treatment. Therefore, mac25 may contribute to the growth
      arrest of U937 cells treated with 1,25-D3. The growth responses to 1alpha,25(OH)2
      D3 and the expression of the mac25 gene of three other cancer cell lines (Saos-2,
      U2OS and MCF7) were studied. Although the growth suppression was observed in MCF7
      cells treated with 1alpha,25(OH)2-D3 dose-dependently (1-100 nM of 1alpha,25(OH)2
      D3), the treatment of 100 nM of 1alpha,25(OH)2-D3 had no effect on the growth of
      Saos-2 and U2OS cells. The expression of the mac25 gene was up-regulated in MCF7
      cells treated with 100 nM of 1alpha,25(OH)2-D3, whereas no transcript of the
      mac25 gene was detected in Saos-2 and U2OS cells even when they were treated with
      100 nM of 1alpha,25(OH)2-D3. These results suggest that the cellular response to
      1alpha,25(OH)2-D3 may depend on the induction of the mac25 gene.

PMID- 11295116
TI  - Induction of RANTES chemokine expression in human astrocytic cells is dependent
      upon activation of NF-kappaB transcription factor.
AB  - RANTES is a C-C (beta)-family chemokine that is implicated in the migration of
      peripheral blood leukocytes to brain lesions in multiple sclerosis (MS), an
      inflammatory demyelinating disease of the central nervous system (CNS). Glial
      cells are active participants in the inflammatory response in the CNS, and they
      have been shown to respond to and produce a number of cytokines and chemokines in
      vivo and in vitro. Recently, we have shown inducibility of RANTES gene expression
      by TNF-alpha in human astrocytic cells. Therefore, the goal of the current study
      was to investigate the transcription activating factor involved in the process.
      We found that the induction of RANTES mRNA and protein by TNF-alpha in human
      astrocytic cells is associated with increased NF-kappaB DNA-binding activity. p65
      and p50 were determined to be the components of the activated NF-kappaB
      transcription factor complex by supershift assay. In addition, the blockade of NF
      kappaB activation by three known NF-kappaB inhibitors markedly reduced the TNF
      alpha-induced RANTES expression at the mRNA and protein levels. Furthermore, the
      reduction in NF-kappaB binding activity to the promoter of the human RANTES gene
      caused by the NF-kappaB inhibitors parallels a decrease in RANTES expression in
      these cells. Our data suggest that NF-kappaB may mediate the induction of RANTES
      gene expression, in human glial cells, through its cognate cis-acting element.

PMID- 11295117
TI  - HHV-8 prevalence, immunosuppression and Kaposi's sarcoma in South Italy.
AB  - The identification of HHV-8 has opened the way for numerous epidemiological
      studies aimed at determining both the prevalence of HHV-8 in various sub-groups
      of the population (affected or not by KS) and at identifying possible cofactors
      necessary for the development of KS. We set up a study to evaluate the prevalence
      of HHV-8 in the South of Italy in KS cases, hospital patients and blood donors
      and to verify the role of immunosuppression in KS. In KS patients the prevalence
      of lytic and latent antigens were both 91% (29 positive cases). Lytic and latent
      antigens have prevalence rates of 20% and 15% respectively in hospital patients.
      In the donor group the rates were 16% for lytic antigens and 2% for latent
      antigens. The most recurrent chronic pathology in KS patients was cardiopathy (5
      cases). The pathological case histories report 4 cases of Herpes Zoster, 6 of
      diabetes, one case of hepatitis C who had also had gonorrea. There was also a
      case, negative to HHV-8, who had had malaria after residing for three years in
      Oristano in Sardinia (a zone with high endemic malaria). Our study confirms that
      in Southern Italy there are relatively high prevalences of HHV-8 both in the
      general population and in blood donors and that immunodysregulation may be
      involved in the pathogenesis of KS. Other studies are necessary to confirm the
      sexual transmission of the HHV-8 virus and to better understand the natural
      history of HHV-8 infection.

PMID- 11295119
TI  - Fine mapping of the PTGFR gene to 1p31 region and mutation analysis in human
      breast cancer.
AB  - The 1p31 chromosomal region shows loss of heterozygosity (LOH) in up to 50% of
      human breast cancer, indicating the presence of a tumor suppressor gene at this
      location. Many efforts have been made to identify candidate genes responsible for
      breast cancer on the short arm of chromosome 1. It was shown that prostaglandins
      have been implicated in the tumorigenesis pathway, perhaps via interactions with
      their cell surface receptors. The prostaglandin F2 receptor gene (PTGFR) was
      tentatively mapped to 1p31 adjacent to the region undergoing LOH in human breast
      cancer. We undertook a mutation study in 34 sporadic human breast tumors using a
      variant of SSCP, incorporation PCR SSCP (IPS). Several nucleotide variants were
      detected in different tumors. Here we report the nature of these nucleotide
      changes and the possible involvement of the PTGFR gene in the etiology of human
      cancer.

PMID- 11295118
TI  - Urocortin reduces oxygen consumption in lean and ob/ob mice.
AB  - A vast number of intensive studies have been undertaken to clarify the mechanisms
      of energy balance. This study was undertaken to investigate the effect of
      urocortin, an endogenous ligand for corticotropin-releasing factor (CRF) type 2
      receptor, on oxygen consumption in lean and genetically obese (ob/ob) mice.
      Oxygen consumption was measured after intraperitoneal injection in unrestrained
      mice at an environmental temperature of 22 degrees C of one of the following:
      urocortin, deamidated form of urocortin (urocortin OH) or CRF. The
      intraperitoneal injection of urocortin (0.3-3 nmol) dose-dependently decreased
      oxygen consumption in lean mice. The inhibitory effect induced by urocortin was
      more potent than that induced by CRF or urocortin OH. The ranking potency was
      urocortin > urocortin OH > CRF. Urocortin significantly reduced oxygen
      consumption in ob/ob mice as well as in lean mice. These results suggest that
      urocortin decreases oxygen consumption, and that the CRF type 2 receptor may
      influence energy balance in lean and ob/ob mice.

PMID- 11295120
TI  - Serological markers for detection of cancer (Review).
AB  - We reviewed the effectiveness of commercial serological markers for the early
      detection of cancer and monitoring cancer patients. Parameters, such as
      specificity and variability of tumor markers were compared with a new approach
      for cancer detection which was recently developed in our laboratory. We
      demonstrate that the absence of tumor specificity and the extremely high
      variability of tumor markers are the reason that none of them can be used for
      early cancer diagnosis. We developed a method for the isolation of tumor
      associated antigens (TAA) and found that two soluble low-molecular mass 66 and 51
      kDa proteins could be isolated from the blood of cancer patients. The first
      protein, albumin, belongs to a group of heat-shock proteins (HSP), while the
      second is connected with TAA. The progress in cancer is characterized by a
      relative decrease in the concentration of HSP and a high increase in blood levels
      of TAA. Our method was shown to be highly sensitive and specific for the early
      detection of different types of cancer, such as of the colon, uterus, ovary, and
      breast, as well as melanoma.

PMID- 11295121
TI  - Expression of CD44 splice variants in spontaneous murine tumors.
AB  - CD44 is a widely distributed set of cell surface glycoproteins expressed in
      several types of cells and tissues, implicated in cell-cell and cell-substrate
      interactions. This molecule plays a major role in cell differentiation,
      development and activation and has also been described as a potential marker of
      malignancy and metastasis. In the present study we investigated by RT-PCR
      followed by exon specific amplification the expression of CD44 splice variants in
      four different murine tumors as well as in the invaded organs in order to
      correlate the expression of CD44 variants with potential tumor invasiveness and
      their implications for growth. Our data showed deregulation in the expression of
      CD44 isoforms but no discernible correlation in isoform expression pattern.
      However, in all tumors studied isoforms presented by the primary tumor were
      detected in the invaded organs before metastasis could be demonstrated by
      histopathological analysis.

PMID- 11295122
TI  - [Mannose-binding protein gene polymorphism influences the patterns of glomerular
      immune deposition in IgA nephropathy].
AB  - OBJECTIVE: To investigate the relationship between mannose-binding protein(MBP)
      gene codon 54 (GGC/GAC) polymorphism and the patterns of glomerular immune
      deposition in IgA nephropathy (IgAN) and explore its functional significance.
      METHODS: IgAN patients were divided into two groups according to the pattern of
      glomerular immune deposition. Group A included 77 patients with glomerular IgA
      and C3 deposits. Group AGM consisted of 70 patients with glomerular IgA, IgG,
      IgM, C3 and Clq deposits. One hundred and forty healthy adults were used as
      normal controls. MBP genotypes were investigated by PCR-RFLP. Serum MBP levels of
      some subjects with different genotypes were also assayed by ELISA simultaneously.
      RESULTS: The genotype frequency of GAC heterozygotes was significantly higher in
      group AGM than in group A (41.4% vs. 19.5%, P<0.01) or normal subjects (41.4% vs.
      26.4%, P<0.05), while no difference was found in the distribution of MBP
      genotypes between group A and normal subjects. The allele frequency of GAC
      mutation was also higher in group AGM than in group A (0.236 vs. 0.136, P<0.05)
      or normal subjects (0.236 vs. 0.146, P<0.05). The variant allele (GAC) was
      markedly associated with group AGM (OR=1.95, 95%CI: 1.06-3.58). In both group A
      and group AGM, more patients carrying the variant allele had episodes of upper
      respiratory or gastrointestinal infections prior to the onset or exacerbation of
      IgAN than wild homozygotes. In addition, a significant difference in serum MBP
      level was also observed among the three genotypes (GGC/GGC>GGC/GAC>GAC/GAC)
      (P<0.0001) for all groups, while there were no differences in serum MBP levels
      for subjects with the same genotypes among the three groups (P>0.05). CONCLUSION:
      The above findings provide evidence that IgAN patients with abundant immune
      deposits in glomeruli show a higher frequency of MBP gene variation which is
      associated with a high frequency of infection and a low serum MBP level. This
      genetic deficiency may lead to an impaired first-line defense and a less
      effective clearance of immune complex than those without this mutation and
      thereafter accelerate glomerular immune deposition during the process of disease.

PMID- 11295123
TI  - [Identification of mutation of the X-linked juvenile retinoschisis gene].
AB  - OBJECTIVE: To elucidate the pathogeny of X-linked retinoschisis(XLRS) and
      evaluate its value in direct gene diagnosis. METHODS: Polymerase chain reaction
      single strand conformation polymorphism(PCR-SSCP) assay was performed to examine
      exons of XLRS1 gene in six unrelated retinoschisis cases (3 families and 3
      sporadic cases), and fragments with a mobility shift were sequenced to identify
      the mutation. The deletion mutations were further identified by Southern blotting
      analysis. RESULTS: Three deletions that eliminate exon 1, exon 2, and exon 3 were
      found in 4 patients of one family. There was severe effect of the mutation in the
      coding region. Three kinds of mutations were found in exon 4: Glu72Lys, Glu72Gln,
      Gly70Ser. CONCLUSION: XLRS is caused by mutation of the XLRS1 gene. The finding
      helps establish a fast and effective direct diagnosis.

PMID- 11295124
TI  - [Studies on neonatal screening, clinical and gene analysis for
      tetrahydrobiopterin deficiency in Southern Chinese].
AB  - OBJECTIVE: To find out the incidence of tetrahydrobiopterin deficiency(BH4D)
      among patients with hyperphenylalaninemia in Southern Chinese and evaluate the
      clinical outcome and gene mutations of tetrahydrobiopterin deficient patients.
      METHODS: Analyses of urinary neopterin(N) and biopterin(B) were done in 87
      patients with hyperphenylalaninemia by high-performance liquid chromatography.
      The patients with BH4 deficiency and their parents were asked to undergo the gene
      mutation analysis and the patients were treated and followed up. RESULTS: Eleven
      cases of which the urinary N/B ratio was higher than 38 and B% lower than 5% were
      diagnosed as BH4 deficiency caused by 6-pyruvoyl-tetrahydropterin synthase(PTPS)
      deficiency. The incidence of BH4 deficiency among patients with
      hyperphenylalaninemia is 12% in Southern Chinese. PTPS gene mutations (P87S,
      N52S, D96N and G144R) were detected from 5 PTPS deficient families. The G144R
      mutation is a new mutation. The five PTPS-deficient patients were treated with
      synthetic BH4, neurotransmitter precursors L-dopa and 5-hydroxytryptophan. They
      had satisfactory physical and mental development after treatment, and 4 of them
      scored their IQ 70-80. CONCLUSION: The screening for BH4 deficiency should be
      carried out in all patients with hyperphenylalaninemia in order to minimize the
      misdiagnoses.

PMID- 11295125
TI  - [Analysis of a case of balanced chromosome translocation and phenotypic
      abnormality by fluorescence in situ hybridization].
AB  - OBJECTIVE: To delineate the chromosome structural aberration in a case of
      chromosome translocation by fluorescence in situ hybridization(FISH) technique
      and precisely identify the breakpoints. METHODS: The whole chromosome point
      5(wcp5) and locus- specific probes derived from yeast artificial
      chromosomes(YACs) mapping the nearby region of breakpoints were used to delineate
      the translocation t(5;10) found by high resolution G-banding examination in a
      case with congenital abnormality. RESULTS: A balanced translocation was confirmed
      and the breakpoints were located in the 1.5 Mb area on chromosome 5 and within
      the approximately 3 Mb interval on chromosome 10. CONCLUSION: The phenotypic
      abnormality might result from the disruption of disease-associated gene(s) or
      microrearrangement(s) on the site of breakpoint(s).

PMID- 11295126
TI  - [Study on apoE gene polymorphism in Chinese endogenous hypertriglyceridemia].
AB  - OBJECTIVE: To investigate apolipoprotein(apo) E polymorphism and its relationship
      with serum lipids and apolipoproteins in Chinese patients with endogenous
      hypertriglyceridemia(HTG). METHODS: apoE genotype was assayed by polymerase chain
      reaction- restriction fragment length polymorphism(PCR-RFLP), serum lipids were
      determined by enzyme method, and apolipoproteins were measured by radial
      immunodiffusion assay in 225 endogenous HTG patients whose fasting serum TG
      levels were > or = 2.26 mmol/L and in 230 healthy subjects whose fasting serum
      lipids levels were TG<1.82 mmol/L, TC<6.21 mmol/L from a population of Chinese
      Han nationality in Chengdu area. RESULTS: Compared with the controls, the values
      of BMI, TG, TC, nHDLC, apoB100, CII, CIII, E and TG/HDLC in HTG patients were
      significantly increased and the values of HDLC, apoAI and apoE/apoCIII were
      significantly decreased(P<0.001). apoE3/3 genotype and allele epsilon(3)
      frequency in HTG group and the control group were both the highest, and allele
      epsilon( 2) frequency in HTG group tended to increase than that in the control
      group(P>0.05). Both in HTG group and control group, the genotype of apoE2 had
      higher serum TG and apoE levels, lower LDLC level and decreased apoE/apoCIII
      ratio as compared with the genotype of apoE3 or apoE4(P<0.001). CONCLUSION:
      Allele epsilon(2) of apoE gene was associated with higher serum TG and apoE
      levels and lower serum LDLC level, and the lower ratio of apoE/apoCIII was
      associated with the higher serum level of TG in endogenous HTG.

PMID- 11295127
TI  - [Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in
      the Han and Li nationalities in Hainan, China and identification of a new
      mutation in human G6PD gene].
AB  - OBJECTIVE: To elucidate the molecular basis of G6PD deficiency in the Han and Li
      nationalities in Hainan, China. METHODS: Polymerase chain reaction and
      restriction enzyme digestion were used to screen the mutations 1388G-->A, 1360C-
      >T, 1024C-->T, 592C-->T, 517T-->C, 493A-->G, 487G-->A, 392G-->T and 95A-->G.
      Single strand conformation polymorphism analysis was used to screen the other
      mutations followed by DNA sequencing to characterize the mutations of the samples
      with abnormal SSCP bands. RESULTS: Of the fifty-nine Han cases with G6PD
      deficiency, fourteen with 1388G-->A (23.7%), three with 871G-->A(5.1%), one with
      835A-->T(1.7%), one with 517T-->C (1.7%), three with 392G-->T(5.1%), and four
      with 95A-->G(6.8%) were found. Of the thirty-two Li cases with G6PD deficiency,
      six with 1388G-->A(18.8%), three with 871G-->A(9.4%), and two with 95A-->G(6.3%)
      were found. A new mutation 835A-->G which causes the substitution of Ala for Thr
      at 279 in a Han case was identified and named as G6PD Haikou. The enzyme activity
      of the variant is about 10% of the normal and lower than the activity of the
      variant 835A-->T with about 40% of the normal. Analysis of the 3D model of human
      G6PD has revealed that the hydroxyl group of Thr at 279 is a group in maintaining
      the interaction of the G6PD subunits. CONCLUSION: The most common mutations of
      G6PD deficiency in Han and Li nationalities in Hainan are similar. Compared with
      the mutation spectrum of G6PD gene in the populations in other regions of China,
      the results indicate that some G6PD gene mutations are widespread in the
      populations of different regions in the southern part of China. The hydroxyl
      group of the Thr at 279 of human G6PD may be a necessary group for maintaining
      the interaction of the G6PD subunits and the enzyme activity.

PMID- 11295128
TI  - [Effect of PAI-1 antisense RNA on vascular endothelial growth factor expression
      in aorta smooth muscle cells cultured in vitro].
AB  - OBJECTIVE: To investigate the role of plasminogen activator inhibitor-1(PAI-1)
      antisense RNA in regulating the expression of PAI-1 and vascular endothelial
      growth factor (VEGF) in aorta smooth muscle cells cultured in vitro. METHODS: The
      second extron of PAI-1 was amplified with polymerase chain reaction(PCR), the
      production was inserted into eukaryotic cell expression vector pcDNA3.1 after it
      had been purified and cloned so as to construct PAI-1 antisense RNA recombination
      plasmid. The recombination plasmid was transfected into SMC. PAI-1 expression was
      detected by immunohistochemistry, Western blod and ELISA; the effects of PAI-1
      variation on VEGF was examined by immunofluorescence. RESULTS: PAI-1 antigen was
      the lowest in cells on the third day after transfection; the expression of VEGF
      was also decreased. PAI-1 antigen gradually increased on the fifth day and VEGF
      increased correspondingly. On the seventh day, PAI-1 antigen and VEGF increased
      to nearly normal level. CONCLUSION: PAI-1 antisense RNA can block the translation
      progress of PAI-1 proteins effectively and inhibit the expression of VEGF in
      aorta smooth muscle cells.

PMID- 11295129
TI  - [Cloning the differentially expressed genes in the retina of rds mouse during the
      development of retinitis pigmentosa].
AB  - OBJECTIVE: To clone the differentially expressed genes in the retina of rds mouse
      (the animal model of congenital retinitis pigmentosa) during the disease
      development. METHODS: The retinal mRNA of rds mouse during the development of
      retinitis pigmentosa was analyzed by the mRNA differential display. The
      differentially expressed mRNA fragments were cloned and sequenced. RESULTS: There
      was obvious difference of gene expression between rds mouse and the control
      during the development of retinitis pigmentosa. Five differentially expressed
      bands were cloned and sequenced. One of those had 86% identity (132/154) with the
      sequence of the human cDNA DKFZp434D1227 from adult testis in GenBank, which was
      submitted lately (15-Oct-1999) and without much information. The other had lower
      identity with the sequences in GenBank. A highly expressed clone in the rds mouse
      on postnatal day 25 had the same length as another clone in the normal on
      postnatal day 37, which was not expressed in the rds mouse on day 37. The
      sequences of the two clones were identical in all but two base pairs. CONCLUSION:
      These results indicate that there are a lot of novel differentially expressed
      genes in the chronic processing diseases, such as retinitis pigmentosa.

PMID- 11295130
TI  - [The relationship between the mutation of methylenetetrahydrofolate reductase
      gene 677C-->T and the diabetic microangiopathy].
AB  - OBJECTIVE: To investigate the relationship between the mutation of methylenetetra
      hydrofolate reductase gene 677C-->T and the diabetic microangiopathy(DMA) in
      diabetes mellitus(DM). METHODS: A total of 168 subjects were divided into control
      group, DM group and DMA group(including diabetic nephropathy and diabetic
      retinopathy). PCR-restrictive fragment length polymorphism(RFLP) analysis was
      conducted to examine mutation, and then the frequency of mutation was
      statistically computed. RESULTS: Markedly elevated mutation was observed in
      patients with diabetic nephropathy and diabetic retinopathy as compared with non
      microangiopathy diabetes mellitus and normal people (20.8% vs 8.3% and 7.3%,
      P<0.01). The odds ratio of the TT genotype for DMA was 3.36, P<0.001. CONCLUSION:
      It was found that the mutation of methylenetetrahydrofolate reductase gene 677C-
      >T was an impressibility factor of diabetic microangiopathy.

PMID- 11295131
TI  - [Polymorphism of MAO-B gene and NAD(P)H: quinone oxidoreductase gene in
      Parkinson's disease].
AB  - OBJECTIVE: To investigate whether Parkinson's disease(PD) is associated with
      genetic polymorphism of intron 13 of monoamine oxidase B(MAO-B) and NAD(P)H:
      quinone oxidoreductase(NQO1) gene cDNA 609C to T. METHODS: Association study was
      performed in 126 PD patients and 136 healthy control subjects matched for age,
      sex and origin. The NQO1 gene polymorphism was analyzed with the polymerase chain
      reaction-restriction fragment length polymorphism, the polymorphism of intron 13
      of MAO-B was analyzed by allele- specific PCR. RESULTS: The allelic frequency of
      the mutant T allele of NQO1 gene was significantly higher in the PD patients as
      compared to the controls(P<0.05). The relative risk of suffering from PD
      increased (OR=3.8) in the individuals with T allelic genotype of NQO1 gene, and
      the odds ratio was as high as 5.7 when the individuals with A or AA genotype of
      MAO-B gene coexisted with the T allele genotype of NQO1 gene. CONCLUSION: The
      cDNA 609T allele of NQO1 gene might be a risk factor of PD, which could be
      associated with the genetic susceptibility of PD. The high activity A or AA
      genotype of MAO-B and the low activity genotype of NQO1 gene might have
      synergistic effect. When both genotypes coexist, the risk of suffering PD will be
      increased greatly.

PMID- 11295132
TI  - [Polymorphisms of the CYP1A1 and GSTM1 genes and their combined effects on
      individual susceptibility to lung cancer in a Chinese population].
AB  - OBJECTIVE: To investigate the polymorphisms of CYP1A1 and GSTM1 genes as well as
      their separate and combined effects on individual susceptibility to lung cancer.
      METHODS: In the matched 106 pairs of patients with lung cancer and non-cancer
      control persons, genomic DNA were prepared from peripheral blood samples. The
      genotypes of CYP1A1 Ile/Val and GSTM1+/0 polymorphisms were detected by the
      allele-specific(AS)-PCR and multidifferential(MD)-PCR. RESULTS: Individuals with
      genotype Val/Val of CYP1A1, genotype 0/0 of GSTM1, combined genotypes GSTM1 0/0
      and CYP1A1 Val/Val, or combined genotypes GSM1 0/0 and CYP1A1 Ile/Val had higher
      relative risk than those with the corresponding common genotypes and combined
      genotypes; their odds ratios were 4.02(P=0.03), 1.92(P=0.019), 9.38(P=0.04) and
      3.27(P=0.01), respectively. CONCLUSION: There is a synergy of susceptible
      genotypes GSTM1 0/0 and CYP1A1 Val/Val or CYP1A1 Ile/Val to enhance the
      individual susceptibility to lung cancer.

PMID- 11295133
TI  - [Expression of tumor suppressor genes p16, p21 and p53 in a pair of lung
      adenocarcinoma cell lines with different metastasis potentials: Anip973 and
      AGZY83-a].
AB  - OBJECTIVE: In order to investigate the suppression effect of tumor suppressor
      genes in lung adenocarcinoma. METHODS: p16 and p21 expression vectors were
      transfected into a pair of lung adenocarcinoma cell lines with different
      metastasis potentials: Anip973(high metastasis potential)and AGZY83-a (low
      metastasis potential). In the mean time, AGZY83-a, Anip973, AGZY83-ap16 and
      Anip973p16 were infected with recombinant adenovirus encoding wild- type p53
      gene. The suppression effects of these genes were evaluated by cell growth curve,
      MTT, cloning efficiency assay, flow cytometric analysis and TUNEL technique.
      RESULTS: Overexpression of p16 gene in Anip973 and AGZY83-a could only lengthen
      the G(1) phase while increased expression of p21 in both of the cell lines was
      associated with significant lengthening of G(1) phase, decreased proliferation
      potential and decreased cloning efficiency. High efficient expression of wild
      type p53 gene in AGZY83-a, Anip973, Anip973p16 and AGZY83-ap16 inhibited the
      growth of these four kinds of lung cancer cells and killed the cells in the end.
      Apoptosis was detected in all the four kinds of cells. The suppression effect of
      p53 gene was higher in Anip973 and Anip973p16 than in AGZY83-a and AGZY83-ap16
      while co-expression of p53 and p16 in this pair of cell lines inhibited the cells
      more efficiently as compared with the expression of p53 gene. CONCLUSION:
      Increased expression of p21 gene suppressed the lung adenocarcinoma cells by G(1)
      arrest and the co-transfection of tumor suppressor genes p16 and p53 into the
      lung adenocarcinoma cell line proved more effective in lung cancer gene therapy.

PMID- 11295135
TI  - [Application of chromosome painting technique to analysis of structural
      aberration of human chromosomes].
AB  - OBJECTIVE: This study was aimed at using chromosome painting technique to detect
      translocation, especially microtranslocations, on chromosomes in comparison with
      G-banding analysis. METHODS: Chromosome painting technique was applied to
      analysis of metaphase chromosomes of patients for detecting translocations with
      biotin-labeled chromosomes X, Y, 14q, 10 specific probes. RESULTS: Fluorescence
      in situ hybridization FISH signals were shown clearly in slides even in specimen
      stored at room temperature for 10 years and at -80 centigrade degree.
      Translocations were located precisely. CONCLUSION: Microtranslocations, which are
      hard to analyze by G-banding, can be detected exactly using chromosome painting
      technique with G-band karyotype on metaphase chromosome.

PMID- 11295134
TI  - [Establishment of platelet-mediated transmitochondrial cell model].
AB  - OBJECTIVE: To establish a transmitochondrial cell model for further researches on
      molecular genetics of mitochondrial related disease. METHODS: The fusion process
      was conducted between mitochondrial DNA-lacking rho degrees cell (a gift from
      NIH) and platelet using polyethylene glycol as fusion promoting reagent. The
      fusion cells were confirmed by PCR and electronic microscopic cytochemistry. The
      mitochondrial morphology and function of 3 families of Rett syndrome were
      investigated. RESULTS: The platelet-mediated transmitochondrial cell model was
      constructed successfully. The frequency of transformation ranged from 0.5 to 1.6
      clones in 10(4) recipient cells. The mitochondrial vacuolation was occasionally
      observed in 2 cases of Rett syndrome. CONCLUSION: Transmitochondrial cell model
      can be applied to assessment of the mitochondrial morphology and function of
      fusion cells and is found to be of great use in evaluating the gene expression of
      mitochondrial genome at different levels.

PMID- 11295136
TI  - [Non-invasive prenatal diagnosis of Duchenne muscular dystrophy].
AB  - OBJECTIVE: This paper was designed to investigate the feasibility of non-invasive
      prenatal diagnosis of Duchenne muscular dystrophy(DMD). METHODS: The nucleated
      red blood cells(NRBC) were separated with percoll using a discontinuous density
      gradient method. The cells were smeared on microscope slides using a cyto
      centrifuge and then stained by Wright- Giemsa. NRBCs were detected and
      individually retrieved into glass capillary pipettes using a micromanipulator
      under microscopic observation. The whole genome of a single cell was amplified by
      improved primer extension preamplification(PEP). The procedures for making
      prenatal diagnosis of DMD and determining the origin of NRBCs proceeded at the
      same time using sex determination and linkage analysis of several STR loci of
      dystrophin. Genotypes were analyzed by amplifying the 9 STR fragments using
      fluorescence-PCR technique and NRBCs origin was further determined. RESULTS: A
      case of DMD in male fetus was diagnosed. CONCLUSION: With the use of the method
      reported, the non-invasive prenatal diagnosis of DMD is possible.

PMID- 11295137
TI  - [Molecular basis of neural-specific gene expression].
AB  - Mammalian central nervous system is a very heterogeneous and complicated system.
      The mechanism of neural-specific gene expression is of considerable general
      interest to scientists. The present paper as a review will focus on the progress
      in this research field.

PMID- 11295138
TI  - [Genetic map and some problems in its mapping and usage].
AB  - Since 1980, with the development of genetic theories and emergence of new
      experimental equipment and techniques, genetic mapping has undergone three
      phases, from restriction fragment length polymorphism, short tandem repeats, to
      single nucleotide polymorphisms. The content of in the genetic map becomes more
      and more informative. So far, the mapping work has nearly ended, however, the
      effort to explore new SNPs locus still continues. The genetic map has begun to
      serve other research purposes and has come to be an indispensable tool to fulfill
      the "functional genome project". In this review are introduced the development of
      genetic map and the genetic maps constructed with three groups of main genetic
      marker. Based on these is a summary of the usage of genetic maps and some
      problems that deserve attention in the use of genetic map, such as the choice of
      genetic markers and the affection of chiasma interference.

PMID- 11295139
TI  - The quintessence of dust.

PMID- 11295140
TI  - An exploratory quantitative risk assessment for high molecular weight
      sensitizers: wheat flour.
AB  - OBJECTIVE: Quantitative risk assessments have been made for wheat dust and
      allergen exposure and wheat sensitization using classical epidemiological
      approaches based on simple categorizations in exposure groups. Such analyses
      suggest the existence of an exposure threshold level for wheat specific
      sensitization and were used as input in recently conducted risk assessments for
      wheat flour by the American Conference of Governmental Industrial Hygienists and
      the Dutch Expert Committee on Occupational Standards. More advanced statistical
      analyses were applied using generalized additive modeling and smoothed plots to
      evaluate the shape of the exposure response relationship in greater detail and
      evaluate the presence of exposure thresholds. METHODS: Data were used from a
      recently conducted epidemiological study in bakery workers. Information was
      available on wheat sensitization (IgE antibodies), inhalable dust levels and
      wheat allergen levels. Initial analyses were based on simple exposure
      categorizations for inhalable dust and allergen exposure. A more detailed
      analysis using non-parametric generalized additive models (GAM models) and
      smoothing plots allowed inspection of the presence of an exposure threshold of
      evaluation of 'no' or 'lowest observed effect levels' (NOELs, LOELs) using
      exposure data on the individual level. RESULTS: All analyses showed an increasing
      sensitization risk with increasing exposure. The classical epidemiological
      analyses gave evidence for the existence of an exposure threshold or 'no observed
      effect level (NOEL)' for specific wheat sensitization between 0.5 and 1 mg/m3 of
      inhalable dust. The more advanced analyses did not suggest any evidence for the
      existence of an exposure threshold. However, estimates of a LOEL obtained by
      considering an arbitrary increase in sensitization risk between 1.5 and 2 as
      undesirable, were close to the NOEL from the classical analyses and would
      therefore not lead to an essentially different exposure limit. The criterion of
      an increase in wheat sensitization risk was based on the risk in non-wheat dust
      exposed populations. CONCLUSION: Exposure response modeling using different
      classical epidemiological approaches and advanced statistical methods resulted in
      health based LOEL or NOEL estimates within a relatively close range. But when
      sensitization accompanied by asthma or rhinitis symptoms was considered as
      critical endpoint, steeper exposure-response relationships were observed which
      would lead to lower LOEL values.

PMID- 11295141
TI  - Effect of process parameters upon the dopamine and lipid peroxidation activity of
      selected MIG welding fumes as a marker of potential neurotoxicity.
AB  - There is growing concern over the neurotoxic effects of chronic occupational
      exposure to metal fume produced by welding. Elevated iron and manganese levels in
      the brain have been linked to an increase in lipid peroxidation, dopamine
      depletion and predisposition to the development of a Parkinson's type condition
      in advanced cases. Chemical and toxicological analysis of selected welding fumes,
      generated by model processes, were used in order to evaluate their potential to
      release solutes that promote oxidation of dopamine and peroxidation of brain
      lipids in cell free assays. This study compared the effect of shield gas,
      electrode type and voltage/currect upon the dopamine and brain lipid peroxidation
      potential of selected welding fume, obtained from metal inert gas (MIG) welding
      systems. Overall, fume extracts were found to enhance dopamine oxidation and
      inhibit lipid peroxidation. Significant differences were also found in the
      oxidising potential of fume generated under differing process conditions; it may
      therefore be possible to determine the potential neurotoxicity of fumes using
      this system.

PMID- 11295142
TI  - Cohort mortality study of North American industrial sand workers. I. Mortality
      from lung cancer, silicosis and other causes.
AB  - BACKGROUND: In 1997 a Working Group of the International Agency for Research on
      Cancer changed an earlier classification of crystalline silica as a human
      carcinogen from Group 2A to Group 1, though commenting that the carcinogenicity
      might vary with industrial circumstances and depend on additional factors
      affecting biological activity, including the distribution of its polymorphs.
      OBJECTIVE: We aimed to determine whether pure quartz exposure uncomplicated by
      the presence of other contaminating carcinogens, as experienced by workers in the
      production of high-grade industrial sand, was causally related to an increased
      risk of lung cancer. METHODS: A cohort of 2670 men employed before 1980 for 3
      years or more in one of nine North American sand-producing plants and a large
      associated office complex was selected for study. Of the cohort, 2644 (99%) were
      traced through 1994, and certificated cause of death ascertained for 1025 (99%)
      of the 1039 men known to have died. Standardised mortality ratios (SMRs) were
      calculated for the main causes of death, using both US and state or provincial
      male mortality rates for reference. FINDINGS: The main analyses of deaths, 20 or
      more years after first employment against regional rates, gave the following
      SMRs: all causes 109, lung cancer 139, other malignancies 98, non-malignant
      respiratory disease 161, and nephritis/nephrosis 244. There were, in total, 37
      deaths from silicosis or silico-tuberculosis, with one or more death at least in
      all nine production plants. Analyses failed to show any relation between lung
      cancer risk and duration of employment. The increased SMR for lung cancer was
      wholly due to high rates in four plants in two states, whereas no increase was
      found in the remainder of the cohort. CONCLUSION: In the absence of information
      on smoking histories and risk in relation to estimated exposure, the increased
      SMR for lung cancer (139), although statistically significant, cannot be
      attributed confidently to crystalline silica. An answer to the question of
      attributability must await the findings of the nested case-control study, in
      which level of exposure and smoking habits were ascertained for cases and matched
      controls. The strong indication in this cohort of excess mortality from non
      malignant renal disease deserves further investigation.

PMID- 11295143
TI  - Cohort mortality study of North American industrial sand workers. II. Case
      referent analysis of lung cancer and silicosis deaths.
AB  - BACKGROUND: A cohort mortality study of 2670 men in nine North American
      industrial sand plants resulted in 83 deaths from lung cancer 20 or more years
      after hire (standardized mortality ratio 139) and 37 deaths from silicosis
      (including seven from silico-tuberculosis). The lung cancer excess was unrelated
      to duration of employment and not found in all plants. OBJECTIVES: The primary
      aim was to determine whether lung cancer risk among these employees was related
      to quantitative estimates of crystalline silica exposure, after allowance for
      cigarette smoking. A secondary aim was to do the same for silicosis mortality,
      partly as a means of validating the estimated levels of exposure. METHODS: A
      nested case-referent study was undertaken with cases matched with up to two
      controls on plant, age and date of first employment from men who survived the
      case. Exposures were estimated by linking work histories to a job-exposure
      matrix, undertaken separately. Cigarette smoking information was obtained from
      medical records and other sources, blind as to case-control status. Matched
      statistical analyses were conducted using conditional logistic regression.
      FINDINGS: Odds ratios for silicosis mortality were significantly related to
      cumulative silica exposures and tended to a relationship with category of average
      crystalline silica concentration, but inconsistently with length of employment.
      After accounting for a strong effect of cigarette smoking, odds ratios for lung
      cancer were related to cumulative crystalline silica exposure and to average
      silica concentration, but not to length of employment. CONCLUSION: These findings
      support a causal relationship between lung cancer and quartz exposure after
      allowance for cigarette smoking, in the absence of cristobalite or other known
      occupational carcinogens.

PMID- 11295144
TI  - Cohort mortality study of North American industrial sand workers. III. Estimation
      of past and present exposures to respirable crystalline silica.
AB  - BACKGROUND: Lung cancer and silicosis mortality were examined longitudinally and
      by a case-referent analysis in a cohort of workers selected from the North
      American industrial sand industry. Date of hire in the case-referent sub-cohort
      extended as far back as the second decade of the twentieth century. OBJECTIVE:
      The aim of this study component was to develop estimates of average and
      cumulative exposure to respirable crystalline silica for the 342 selected cases
      and referents. METHODS: Process and dust control histories were developed for
      each plant, and quantitative exposure data obtained from each of them and from a
      trade organization. An algorithm was developed to convert historical exposures
      reported in particle count concentrations to modern measures of mass
      concentration of respirable crystalline silica. Personal exposures were adjusted
      for use of protective equipment based on frequency of use and type of protection.
      FINDINGS: Between 1974 and 1998, a total of 14249 exposure measurements had been
      taken using a cyclone and membrane filter and gave an overall geometric mean of
      42 microg/m3. The only exposure data identified earlier were based on
      approximately 500 samples collected across the industry between 1947 and 1955
      using the Greenburg-Smith impinger, with analysis by microscopy. These data were
      converted to modern measures using a factor of 1 mppcf = 276 microg/m3 respirable
      dust and then adjusting for percentage silica. In general, the highest exposures
      occurred in bagging and bulk-loading operations and the lowest in wet processing
      of sand. CONCLUSIONS: There has been a substantial decline in exposure levels in
      this industry over time. The decline was rapid between the 1940s and 1970s and
      current exposures are, on average, less than 50 microg/m3. The use of personal
      protective equipment was judged to have had little impact on exposure before the
      1970s.

PMID- 11295145
TI  - Inhalation exposure in secondary aluminium smelting.
AB  - Inhalation exposure at seven UK secondary aluminium smelters was investigated to
      quantify the main exposures and identify their sources. The substances monitored
      were gases (carbon monoxide, hydrogen sulphide and nitrogen dioxide), total
      inhalable dust, metals, ammonia, polycyclic aromatic hydrocarbons (PAHs),
      particulate fluoride salts and acids. The results showed that people were exposed
      to a range of workplace air pollutants. Personal exposure results for total
      inhalable dust were between 700 and 5600 microg x m(-3) and the maximum personal
      exposure result for particulate fluoride salts was 690 microg x m(-3) (as F). The
      maximum aluminium, total PAH and lead personal exposure results were 900, 19 and
      18 microg x m(-3) respectively. The average proportion of aluminium in total
      inhalable dust samples was 13% and rotary furnace processes generated the most
      dust. Particulate fluoride salt exposure was more widespread than hydrofluoric
      acid exposure. The source of the salt exposure was fluoride containing fluxes.
      The lead exposure source was lead solder contamination in the furnace charge.

PMID- 11295146
TI  - Distributions and determinants of pre-emergent herbicide exposures among custom
      applicators.
AB  - Custom applicators intensively apply herbicides to corn and soybean fields each
      spring. The primary objective of this study was to characterize the exposure
      distributions of the herbicides alachlor, atrazine, 2,4-D 2-ethylhexyl ester (2,4
      D EH), and metolachlor among a group of applicators during the spring pre
      emergent spray season. A secondary objective was to evaluate determinants of
      exposure and to estimate within- and between-worker variance components. Fifteen
      applicators were sampled using a systematic design that included spray and non
      spray days and multiple measurements (five to seven) on each applicator. Air,
      patch, and handwash samples were collected on 89 applicator-days. Applicator-days
      were classified into three categories: target herbicide sprayed, non-target
      herbicide sprayed, and no herbicide sprayed. Mixed-model regression analysis was
      used. For all exposure metrics, adjusted mean herbicide exposures were
      significantly higher on days when target herbicides were sprayed as compared to
      non-spray days. For 2,4-D EH only, adjusted mean exposures on non-target
      herbicide spray days were significantly higher than on non-spray days. Wearing
      gloves significantly reduced adjusted mean hand exposure for all herbicides (4-20
      fold) and adjusted mean thigh exposure for three herbicides (8-53 fold) on days
      the herbicides were sprayed; however, wearing gloves significantly increased
      adjusted mean atrazine hand and thigh exposures (9 and 7 fold, respectively) on
      days that non-atrazine herbicides were sprayed. Few of the other covariates were
      consistent determinants of exposure. For all exposure metrics, the within-worker
      variability (GSD(W) 2.1-5.6) was greater than the between-worker variability
      (GSD(B) 1.2-2.7).

PMID- 11295147
TI  - Weighing imprecision and handleability of the sampling cassettes of the IOM
      sampler for inhalable dust.
AB  - The weight stability of the sampling cassette of the IOM sampler for inhalable
      dust was tested in several weighing experiments. The results show that the
      reliability of repeated weighings was good, but the absorption of water vapour
      was slow and varied considerably among cassette specimen. The exponential time
      constant for water absorption was approximately 4 days, and 15-20 days were
      needed to obtain weight stability. With the help of cassette blanks the
      imprecision in dust weight could be held below 0.05 mg, if the cassettes were
      allowed one week's storage in the weighing room before weighing, both before and
      after sampling. The IOM sampling cassettes seem to consist of a few subsets, each
      with identical relative weight increase in a weighing room. To keep the
      variability low it is important that both the blanks and the cassettes used for
      sampling come from the same subset. Experiments indicate that the conducting
      plastic of the IOM sampling cassette may be replaced with another kind of plastic
      with similar electrical conductivity, but whose humidity absorption is 30 times
      lower. A lid, which is weighed with the cassette, was designed so that the
      potential dust loss from the cassette proper to the commercial transport clip was
      eliminated. A flow adapter, which simplifies the measurement of the air flow
      during personal sampling, was designed.

PMID- 11295148
TI  - Vitamins/minerals and genomic stability in humans.
AB  - Recommended dietary allowances (RDAs) of micronutrients have been traditionally
      derived as those levels necessary to prevent symptoms of deficiency diseases.
      There is increasing evidence that higher levels of many such micronutrients may
      be necessary for various DNA maintenance reactions, and that the current RDAs for
      some micronutrients may be inadequate to protect against genomic instability.
      Supplementation of a normal diet, with either vitamins and/or minerals or with
      isolated plant polyphenols, is becoming increasingly common in most Western
      populations. However, there is no clear agreement as to how much supplementation
      should occur, if at all, and genotypic differences are not accounted for. The 14
      mini-reviews in this special issue summarise the role of specific micronutrients
      in various aspects of DNA maintenance: DNA synthesis, DNA repair, DNA
      methylation, gene mutation, chromosome breakage, chromosome segregation, gene
      expression, oxidative stress, necrosis and apoptosis. Evidence has been collated
      from mammalian and human experiments, both using in vitro cultures and in vivo
      approaches. Authors were asked to critically assess the strength of evidence as
      to whether the micronutrient can affect genomic stability in humans at realistic
      intake levels, and to estimate optimal dietary ranges where possible. Information
      on further research necessary is also documented. These reviews are an essential
      step towards a definition of RDAs designed to maintain genomic stability.

PMID- 11295149
TI  - DNA damage from micronutrient deficiencies is likely to be a major cause of
      cancer.
AB  - A deficiency of any of the micronutrients: folic acid, Vitamin B12, Vitamin B6,
      niacin, Vitamin C, Vitamin E, iron, or zinc, mimics radiation in damaging DNA by
      causing single- and double-strand breaks, oxidative lesions, or both. For
      example, the percentage of the US population that has a low intake (<50% of the
      RDA) for each of these eight micronutrients ranges from 2 to >20%. A level of
      folate deficiency causing chromosome breaks was present in approximately 10% of
      the US population, and in a much higher percentage of the poor. Folate deficiency
      causes extensive incorporation of uracil into human DNA (4 million/cell), leading
      to chromosomal breaks. This mechanism is the likely cause of the increased colon
      cancer risk associated with low folate intake. Some evidence, and mechanistic
      considerations, suggest that Vitamin B12 (14% US elderly) and B6 (10% of US)
      deficiencies also cause high uracil and chromosome breaks. Micronutrient
      deficiency may explain, in good part, why the quarter of the population that eats
      the fewest fruits and vegetables (five portions a day is advised) has about
      double the cancer rate for most types of cancer when compared to the quarter with
      the highest intake. For example, 80% of American children and adolescents and 68%
      of adults do not eat five portions a day. Common micronutrient deficiencies are
      likely to damage DNA by the same mechanism as radiation and many chemicals,
      appear to be orders of magnitude more important, and should be compared for
      perspective. Remedying micronutrient deficiencies should lead to a major
      improvement in health and an increase in longevity at low cost.

PMID- 11295150
TI  - Carotenoids and genomic stability.
AB  - Epidemiological evidence abounds for a link between intake of carotenoids from
      fruit and vegetable foods and relatively low incidence of various cancers.
      However, intervention trials have shown, in some cases, a significant increase in
      occurrence of lung cancer in those volunteers taking supplements of beta
      carotene. More information is clearly needed about the mechanism of action of
      carotenoids. Effects of carotenoids on cells in culture include inhibition of DNA
      synthesis and proliferation, changes in gene expression, decreased micronucleus
      frequency, and inhibition of transformation via synthesis of gap-junction
      proteins. Experiments with animal models are unsatisfactory because of the very
      poor uptake of carotenoids in rodents compared with man. In humans, oxidative
      damage to lymphocytes correlates negatively with plasma carotenoid
      concentrations, and the level of DNA damage is susceptible to reduction by
      carotenoid-rich foods. It seems clear that the carotenoids act as antioxidants in
      vivo, and yet this activity may not result in cancer prevention.

PMID- 11295151
TI  - Vitamin C and genomic stability.
AB  - Vitamin C, a water-soluble glucose derivative, has considerable antioxidant
      activity in vitro, in part because of its ease of oxidation and because the
      semidehydroascorbate radical derived from it is of low reactivity. Vitamin C in
      vivo is an essential cofactor for a range of enzymes involved in diverse
      metabolic pathways, but much recent literature has focused on its antioxidant
      effects. Consumption of foods rich in Vitamin C (fruits and vegetables) is
      associated with decreased risk of cardiovascular disease, of many types of cancer
      and possibly of neurodegenerative disease, but the extent to which Vitamin C
      contributes to these effects is uncertain. Data using biomarkers of oxidative
      damage to DNA bases have given no compelling evidence to date that ascorbate
      supplements can decrease the levels of oxidative DNA damage in vivo, except
      perhaps in subjects with very low Vitamin C intakes. Similarly, there is no
      conclusive evidence from studies of strand breaks, micronuclei, or chromosomal
      aberrations for a protective effect of Vitamin C. There is limited evidence that
      supplements of Vitamin C might have beneficial effects in disorders of vascular
      function, and that diet-derived Vitamin C may decrease gastric cancer incidence
      in certain populations, but it is not clear whether it is the antioxidant or
      other properties of ascorbate that are responsible for these two actions.

PMID- 11295152
TI  - Vitamin E and genome stability.
AB  - Free radicals and reactive oxygen species (ROS) which are generated continuously
      cause mutagenic alterations resulting in cancer, aging and abnormalities in the
      nervous system. Accumulating evidence indicates that Vitamin E, the most potent
      lipid peroxyl radical scavenger, may reduce free radical induced chromosomal
      damages through inhibition of free radical formation, and activation of
      endonuclease that can be triggered by intracellular oxidative stress, and by
      increasing the rate of removal of damaged DNA. Although some studies suggest a
      potential usefulness of Vitamin E in the prevention of mutagenic effects caused
      by genotoxic free radicals, other studies report no effects. Thus the data are
      not conclusive enough to be used as a basis to change the current recommended
      dietary allowances (RDA). Future research should address molecular mechanisms
      underlying the protective effects of Vitamin E and develop appropriate
      biologically relevant biomarkers of DNA damage to further help in determining the
      dietary levels of Vitamin E needed to protect the genetic pool from internally
      and externally induced DNA damages.

PMID- 11295153
TI  - Niacin, poly(ADP-ribose) polymerase-1 and genomic stability.
AB  - Nicotinic acid (NA) and nicotinamide (NAM), commonly called niacin, are the
      dietary precursors for NAD(+) (nicotinamide adenine dinucleotide), which is
      required for DNA synthesis, as well as for the activity of the enzyme poly(ADP
      ribose) polymerase-1 (PARP-1; EC 2.4.2.30) for which NAD(+) is the sole
      substrate. The enzyme PARP-1 is highly activated by DNA strand breaks during the
      cellular genotoxic stress response, is involved in base excision repair, plays a
      role in p53 expression and activation, and hence, is thought to be important for
      genomic stability. In this review, first the absorption, metabolism of niacin to
      NAD(+), as well as the assessment of niacin status are discussed. Since NAD(+) is
      important for PARP-1 activity, various aspects of PARP-1 in relation to DNA
      synthesis and repair, and regulation of gene expression are addressed. This is
      followed by a discussion on interactions between dietary methyl donor deficiency,
      niacin status, PARP-1 activity and genomic stability. In vitro studies show that
      PARP-1 function is impaired and genomic stability decreased when cells are either
      depleted from NAD(+) or incubated with high concentrations of NAM which is a PARP
      1 inhibitor. In vitro as well as animal studies indicate that niacin deficiency
      increases genomic instability especially in combination with genotoxic and
      oxidative stress. Niacin deficiency may also increase the risk for certain
      tumors. Preliminary data suggest that niacin supplementation may protect against
      UV-induced tumors of the skin in mice, but data on similar preventive effects in
      humans are not available. NAM has been shown in vitro to have an antioxidant
      activity comparable to that of ascorbic acid. Data on niacin status and genomic
      stability in vivo in humans are limited and yield ambiguous results. Therefore,
      no firm conclusions with respect to optimal niacin intake are possible. As a
      consequence of oral niacin supplementation, however, NAM levels in the body may
      increase, which may result in inhibition of PARP-1 and increased genomic
      instability. More studies are needed to define an optimal level of niacin
      nutriture in relation to genomic stability and tumorigenesis.

PMID- 11295154
TI  - The role of folic acid and Vitamin B12 in genomic stability of human cells.
AB  - Folic acid plays a critical role in the prevention of chromosome breakage and
      hypomethylation of DNA. This activity is compromised when Vitamin B12 (B12)
      concentration is low because methionine synthase activity is reduced, lowering
      the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA
      methylation and cause folate to become unavailable for the conversion of dUMP to
      dTMP. The most plausible explanation for the chromosome-breaking effect of low
      folate is excessive uracil misincorporation into DNA, a mutagenic lesion that
      leads to strand breaks in DNA during repair. Both in vitro and in vivo studies
      with human cells clearly show that folate deficiency causes expression of
      chromosomal fragile sites, chromosome breaks, excessive uracil in DNA,
      micronucleus formation and DNA hypomethylation. In vivo studies show that Vitamin
      B12 deficiency and elevated plasma homocysteine are significantly correlated with
      increased micronucleus formation. In vitro experiments indicate that genomic
      instability in human cells is minimised when folic acid concentration in culture
      medium is >227nmol/l. Intervention studies in humans show: (a) that DNA
      hypomethylation, chromosome breaks, uracil misincorporation and micronucleus
      formation are minimised when red cell folate concentration is >700nmol/l folate;
      and (b) micronucleus formation is minimised when plasma concentration of Vitamin
      B12 is >300pmol/l and plasma homocysteine is <7.5micromol/l. These concentrations
      are achievable at intake levels in excess of current RDIs i.e. more than 200
      400microgram folic acid per day and more than 2microgram Vitamin B12 per day. A
      placebo-controlled study with a dose-response suggests that based on the
      micronucleus index in lymphocytes, an RDI level of 700microgram/day for folic
      acid and 7microgram/day for Vitamin B12 would be appropriate for genomic
      stability in young adults. Dietary intakes above the current RDI may be
      particularly important in those with extreme defects in the absorption and
      metabolism of these Vitamins, for which ageing is a contributing factor.

PMID- 11295155
TI  - Vitamin D and genomic stability.
AB  - 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] has been shown to act on novel
      target tissues not related to calcium homeostasis. There have been reports
      characterizing 1,25(OH)(2)D(3) receptors and activities in diverse tissues such
      as brain, pancreas, pituitary, skin, muscle, placenta, immune cells and
      parathyroid. The receptor hormone complex becomes localized in the nucleus, and
      undergoes phosphorylation by reacting with a kinase. This form of the receptor
      then interacts with the Vitamin D responsive element of target gene and modifies
      the transcription of those genes to develop the action. The modulation of gene
      transcription results in either the induction or repression of specific messenger
      RNAs (m-RNAs), ultimately resulting in changes in protein expression needed to
      produce biological responses. Genes for carbonic anhydrase that are expressed at
      high levels in osteoclast are known to be involved in bone resorption and Id
      genes role in osteoblast-osteoclast differentiation reflects the genomic effect
      of Vitamin D on bones. Genomic action of Vitamin D also explains the biosynthesis
      of oncogenes, polyamines, lymphokines and calcium binding proteins. However,
      there is a possibility that some of the actions of 1,25(OH)(2)D(3) may be
      mediated by non-genomic mechanisms and may not require the binding to Vitamin D
      receptor (VDR). Vitamin D offers a protection from genotoxic effects of Vitamin D
      deficiency by increasing the insulin receptor gene expression and BSP (bone
      sialoprotein), bone-remodeling by decreasing the osteopontin (OPN) m-RNAs,
      maintaining the normal epidermal structure and enamel matrix. Gonadal
      insufficiency in Vitamin D deficiency was corrected by vitamin mediated direct
      regulation of the expression of aramotase gene. The supportive role of Vitamin D
      in placental function is also evident by its influence on human placental
      lactogen (hpl) gene transcription accompanied by increase hpl m-RNA levels.
      Further role of Vitamin D is envisaged in identifying cyclin C as an important
      target for Vitamin D in cell-cycle regulation. Vitamin D at physiological
      concentration has been found to protect cell proteins and membranes against
      oxidative stress by inhibiting the peroxidative attack on membrane lipids.
      Vitamin D, at a concentration range of 2x10(-8)-5x10(-8)M, induces apoptosis in
      most cancer cells, stabilizes chromosomal structure and prevents DNA double
      strand breaks induced either by endogenous or exogenous factors. Vitamin D is
      also effective in stimulating DNA synthesis in adult alveolar II cells and
      provides a novel mechanism of modulation of epithelial cell proliferation in the
      context of lung development and repair against injury. The regulation of various
      proto-oncogenes (c-myc, c-fos, c-jun), differentiation inducing properties,
      antiproliferative effects on keratinocytes and inhibitory effects in several
      human malignancy ranks Vitamin D as a novel hormone that may have physiological
      and clinical implication in the carcinogenic process.

PMID- 11295156
TI  - Role of plant polyphenols in genomic stability.
AB  - Polyphenols are a large and diverse class of compounds, many of which occur
      naturally in a range of food plants. The flavonoids are the largest and best
      studied group of these. A range of plant polyphenols are either being actively
      developed or currently sold as dietary supplements and/or herbal remedies.
      Although, these compounds play no known role in nutrition (non-nutrients), many
      of them have properties including antioxidant, anti-mutagenic, anti-oestrogenic,
      anti-carcinogenic and anti-inflammatory effects that might potentially be
      beneficial in preventing disease and protecting the stability of the genome.
      However not all polyphenols and not all actions of individual polyphenols are
      necessarily beneficial. Some have mutagenic and/or pro-oxidant effects, as well
      as interfering with essential biochemical pathways including topoisomerase enzyme
      activities, prostanoid biosynthesis and signal transduction. There is a very
      large amount of in vitro data available, but far fewer animal studies, and these
      are not necessarily predictive of human effects because of differences in
      bacterial and hepatic metabolism of polyphenols between species. Epidemiological
      studies suggest that high green tea consumption in the Japanese population and
      moderate red wine consumption in the French population may be beneficial for
      heart disease and cancer, and these effects may relate to specific polyphenols. A
      small number of adequately controlled human intervention studies suggest that
      some, but not all polyphenol extracts or high polyphenol diets may lead to
      transitory changes in the antioxidative capacity of plasma in humans. However,
      none of these studies have adequately considered long-term effects on DNA or the
      chromosome and unequivocally associated these with polyphenol uptake.
      Furthermore, clinical trials have required intravenously administered polyphenols
      at concentrations around 1400mg/m(2) before effects are seen. These plasma
      concentrations are unlikely to be achieved using the dietary supplements
      currently available. More focused human studies are necessary before recommending
      specific polyphenolic supplements at specific doses in the human population.

PMID- 11295157
TI  - Role of magnesium in genomic stability.
AB  - In cellular systems, magnesium is the second most abundant element and is
      involved in basically all metabolic pathways. At physiologically relevant
      concentrations, magnesium itself is not genotoxic, but is highly required to
      maintain genomic stability. Besides its stabilizing effect on DNA and chromatin
      structure, magnesium is an essential cofactor in almost all enzymatic systems
      involved in DNA processing. Most obvious in studies on DNA replication, its
      function is not only charge-related, but very specific with respect to the high
      fidelity of DNA synthesis. Furthermore, as essential cofactor in nucleotide
      excision repair, base excision repair and mismatch repair magnesium is required
      for the removal of DNA damage generated by environmental mutagens, endogenous
      processes, and DNA replication. Intracellular magnesium concentrations are highly
      regulated and magnesium acts as an intracellular regulator of cell cycle control
      and apoptosis. As evident from animal experiments and epidemiological studies,
      magnesium deficiency may decrease membrane integrity and membrane function and
      increase the susceptibility to oxidative stress, cardiovascular heart diseases as
      well as accelerated aging. The relationship to tumor formation is more complex;
      magnesium appears to be protective at early stages but promotes the growth of
      existing tumors. With respect to the magnesium status in humans, the daily intake
      in most industrialized countries does not reach the current recommended daily
      dietary allowances (RDA) values, and thus marginal magnesium deficiencies are
      very common.

PMID- 11295158
TI  - The protective role of selenium on genetic damage and on cancer.
AB  - Collectively, results from epidemiologic studies, laboratory bioassays, and human
      clinical intervention trials clearly support a protective role of selenium
      against cancer development. Several hypotheses have been proposed to explain
      these observations. Increased genomic instability, either inherent or induced by
      exogenous agents (mutagens or carcinogens), has been considered as a primary
      event leading to neoplastic transformation. This report deals specifically with
      the evidence for a role of selenium in the inhibition of carcinogen-induced
      covalent DNA adduct formation and retardation of oxidative damage to DNA, lipids
      and proteins, and for modulating cellular and molecular events that are critical
      in cell growth inhibition and in the multi-step carcinogenesis process. At
      present, the bulk of our knowledge on the role of selenium on genetic stability
      is based primarily on animal data and from studies conducted in in vitro systems.
      Studies performed in vitro showed that the dose and form of selenium compounds
      are critical factors with regard to cellular responses. Inorganic (at doses up to
      10microM) and organic selenium compounds (at doses equal to or greater than
      10microM) elicit distinctly different cellular responses. The recommended daily
      allowance (RDA) is 50-70 microgramSe per day for healthy adults; with 40
      microgramSe as minimum requirement. Less than 11 microgramSe will definitely put
      people at risk of deficiency that would be expected to cause genetic damage.
      Daily doses of 100-200 microgramSe inhibited genetic damage and cancer
      development in humans. About 400 microgramSe per day is considered an upper
      limit. Clearly, doses above the RDA are needed to inhibit genetic damage and
      cancer. However, it has been hypothesized that the intake of excessive doses of
      selenium may cause oxidative damage, leading to genomic instability. The use of a
      cocktail consisting of selenium, and other vitamins and minerals appears to be a
      promising approach to inhibit genetic damage and the development of cancer. It is
      the author's recommendation that development of mechanism-based hypotheses that
      can be tested in pilot studies in different populations prior to a large-scale
      clinical trial in humans, is of paramount importance in order to better
      understand the role of selenium on genetic stability and cancer.

PMID- 11295159
TI  - Copper and genomic stability in mammals.
AB  - As the free ion and in the form of some complexes, there is no doubt that copper
      can promote damage to cellular molecules and structures through radical
      formation. At the same time, and perhaps as a consequence, mammals have evolved
      means of minimizing levels of free copper ions and destructive copper complexes
      that enter the organism and its cells. These means include tight binding of
      copper ions to protein carriers and transporters; direct exchange of copper
      between protein carriers, transporters, and cuproenzymes; and mobilization of
      secretory mechanisms and excretory pathways, as needed. As a consequence,
      normally, and except under certain genetic conditions, copper is likely to be
      benign to most mammals and not responsible for genomic instability, including
      fragmentation of and/or alterations to DNA, induction of mutations or apoptosis,
      or other toxic events. Indeed, cuproenzymes are important members of the
      antioxidant system of the organism.

PMID- 11295160
TI  - Iron and its sensitive balance in the cell.
AB  - Iron is vital in life because it is an important component of molecules that
      undergoes redox reactions or transport oxygen. However, the existence of two
      stable and inter-convertible forms of iron, iron(III) and iron(II), makes
      possible one electron being transferred to or captured from other species to form
      radicals. In particular, superoxide and hydroxyl radicals may be formed in these
      reactions, both with capacity of attacking other molecules. DNA is one important
      target and a vast literature exists showing that attack of hydroxyl radical to
      DNA leads to cell death cellular necrosis, apoptosis, mutation and malignant
      transformation. Therefore, a fine balance must exist at various levels of an
      organism to maintain iron concentration in a narrow range, above and below which
      deleterious effects of distinct nature occur. This review will deal with the
      formation of oxygen reactive species in iron participating reactions, defenses in
      the organism against these species, the different mechanisms of iron homeostasis
      and iron deficiency and iron overload related diseases.

PMID- 11295161
TI  - Zinc and the gene.
AB  - A significant portion of cellular zinc is found in the nucleus where it appears
      to be critically involved in maintaining genetic stability and in the process of
      gene expression. With regard to gene expression zinc functions mechanistically at
      several levels but recent interest has focussed especially on the involvement of
      zinc in DNA transcription through the activity of transcription factors which
      contain specific zinc-finger regions which bind to DNA and, in conjunction with
      other families of transcription factors, control cell proliferation,
      differentiation and cell death. Because of the central importance of zinc in cell
      division and growth, considerable attention is paid to zinc as an essential trace
      element and much has been written concerning dietary sources of zinc and
      recommended dietary intakes of the metal.

PMID- 11295162
TI  - Mitochondrial DNA in aging and degenerative disease.
AB  - The mitochondrial DNA encodes only a few gene products compared to the nuclear
      DNA. These products, however, play a decisive role in determining cell function.
      Should this DNA mutate spontaneously or be damaged by free radicals the
      functionality of the gene products will be compromised. A number of mitochondrial
      genetic diseases have been identified. Some of these are quite serious and
      involve the central nervous system as well as muscle, heart, liver and kidney.
      Aging has been characterized by a gradual increase in base deletions in this DNA.
      This increase in deletion mutation has been suggested to be the cumulative result
      of exposure to free radicals.

PMID- 11295163
TI  - Stomatal density and stomatal index as indicators of paleoatmospheric CO(2)
      concentration.
AB  - A growing number of studies use the plant species-specific inverse relationship
      between atmospheric CO(2) concentration and stomatal density (SD) or stomatal
      index (SI) as a proxy for paleo-CO(2) levels. A total of 285 previously published
      SD and 145 SI responses to variable CO(2) concentrations from a pool of 176 C(3)
      plant species are analyzed here to test the reliability of this method. The
      percentage of responses inversely responding to CO(2) rises from 40 and 36% (for
      SD and SI, respectively) in experimental studies to 88 and 94% (for SD and SI,
      respectively) in fossil studies. The inconsistent experimental responses verify
      previous concerns involving this method, however the high percentage of fossil
      responses showing an inverse relationship clearly validates the method when
      applied over time scales of similar length. Furthermore, for all groups of
      observations, a positive relationship between CO(2) and SD/SI is found in only
      </=12% of cases. Thus, CO(2) appears to inversely affect stomatal initiation,
      although the mechanism may involve genetic adaptation and therefore is often not
      clearly expressed under short CO(2) exposure times.Experimental responses of SD
      and SI based on open-top chambers (OTCs) inversely relate to CO(2) less often
      than greenhouse-based responses (P<0.01 for both SD and SI), and should be
      avoided when experimental responses are required for CO(2) reconstructions. In
      the combined data set, hypostomatous species follow the inverse relationship more
      often than amphistomatous species (56 vs. 44% for SD; 69 vs. 32% for SI; P<0.03
      for both comparisons). Both the SD and SI of fossil responses are equally likely
      to inversely relate to CO(2) when exposed to elevated versus subambient CO(2)
      concentrations (relative to today). This result casts doubt on previous claims
      that stomata cannot respond to CO(2) concentrations above present-day levels.
      Although the proportion of SD and SI responses inversely relating to CO(2) are
      similar, SD is more strongly affected by various environmental stresses, and thus
      SI-based CO(2) reconstructions are probably more accurate.

PMID- 11295164
TI  - Modern pollen studies in the territory of Sagalassos (Southwest Turkey) and their
      use in the interpretation of a Late Holocene pollen diagram.
AB  - Modern pollen precipitation studies were carried out on a regional scale in the
      territory of the classical city of Sagalassos (Southwest Turkey). 57 moss
      cushions and 7 soil samples from different vegetation types were analysed
      palynologically. The resulting pollen spectra were grouped into 14 vegetation
      groups, which were examined using discriminant analysis and principal components
      analysis. These numerical procedures are applied to display the structure in the
      data set in a comprehensive way. Some of the modern spectra groups seem to be
      well-defined, whereas others are difficult to distinguish from each other. After
      the relationships between the modern pollen spectra had been analysed, the fossil
      data from a core from the marsh of Gravgaz were added to the data set so that any
      similarities between fossil and modern spectra could be seen. A joint principal
      components analysis of the modern and fossil pollen spectra revealed that the
      pollen spectra from the earliest (ca. 2600-2500 BP; Cal. 830-590 BC till 790-520
      BC) and the latest (starting at ca. 1300 BP; Cal. 660-780 AD) pollen assemblage
      zones have modern counterparts. On the other hand, the pollen spectra from the
      pollen assemblage zone dominated by Artemisia (ca. 2500-2300 BP; Cal. 790-520 BC
      till 410-210 BC) and from the pollen assemblage zone that indicated the practice
      of arboriculture (ca. 2300-1300 BP; Cal. 410-210 BC till 660-780 AD) have no
      close modern analogues, although individual tabulated pollen percentages revealed
      some similarities with some modern spectra groups.

PMID- 11295165
TI  - Two species of Selaginella cones and their spores from the Bohemian Carboniferous
      continental basins of the Czech Republic.
AB  - Two species of Selaginella cones from the Bohemian Upper Carboniferous
      continental basins of the Bolsovian and Westphalian D age are described, together
      with their in situ spores. Two specimens of Selaginella gutbierii yielded
      microspores closely comparable with the dispersed species Cirratriradites
      saturnii and megaspores closely comparable with the dispersed species
      Triangulatisporites vermiculatus. Microspores closely comparable with the
      dispersed species Cirratriradites annulatus and megaspores resemble the dispersed
      species Triangulatisporites tertius were isolated from cones of Selaginella cf.
      leptostachys. All the spores isolated from one cone are of the same type and
      would be referred to one dispersed micro- and megaspore species if found as
      Sporae dispersae. The paper contains a review of all palynologically studied
      Carboniferous Selaginella and Selaginella-like cones and reviews of all in situ
      and dispersed Cirratriradites and Triangulatisporites spores.

PMID- 11295166
TI  - Comparing Early to Middle Miocene floras and probable vegetation types of
      Oberdorf N Voitsberg (Austria), Bohemia (Czech Republic), and Wackersdorf
      (Germany).
AB  - The Early Miocene vegetation of western Styria, Austria, is reconstructed on the
      basis of detailed investigations of leaves and diaspores from the mining area
      Oberdorf N Voitsberg. In this paper, the flora and probable vegetation are
      compared with other assemblages of similar age from the Czech Republic and
      Germany to elucidate the diversity of wetland and mesophytic plant communities.
      The floristic composition and the vegetational units represented in Oberdorf are
      compared to the middle part of the Most Formation (M Most Fm), Cypris Shale,
      Mydlovary Formation (Mydlovary Fm) of Bohemia, and the Wackersdorf mining area of
      Bavaria. Among these sites, Oberdorf is extremely poor in hydrophytes and reed
      like monocotyledons, indicating rare pond-like habitats as well as possibly more
      closed swamp forest conditions than, e.g. in the M Most Fm. In Oberdorf,
      relatively high pH-values in the lignite-forming swamps and the possible scarcity
      of acidic, nutrient-poor (sandy) soils have probably influenced the floristic
      composition of the azonal communities. The peat-forming associations in all
      regions share the abundance of Glyptostrobus europaeus. However, distinct
      differences in the accompanying elements, such as Taxodium dubium (present and
      abundant only in the M Most Fm) indicate even stronger floristic variability of
      Early(/Middle) Miocene peat-forming and riparian plant communities than
      previously expected. The virtual absence of Pinus, Engelhardia, Comptonia, and
      probably also of Quercus kubinyii/Quercus drymeja in the megafossil record of
      Oberdorf can possibly be explained by the edaphic conditions. The abundance of
      Sequoia abietina (absent in all the other compared sites), which we assign to
      riparian (and mesophytic) forests in Oberdorf, may have been favoured by rich
      alluvial soils.In the mesophytic associations, thermophilous elements of the
      Lauraceae, Mastixiaceae, Symplocaceae, and Rutaceae are diverse. Usually they
      include Trigonobalanopsis rhamnoides/Trigonobalanopsis exacantha, an evergreen
      Fagaceae. This assemblage type corresponds with the Younger Mastixioid Flora
      sensu Mai. The Younger Mastixioid Flora is best developed in Wackersdorf, less
      distinct in Oberdorf, and likely in the Cypris Shale and Mydlovary Fm. It is not
      traceable in the M Most Fm.

PMID- 11295167
TI  - Permineralized Callixylon woods from the Late Devonian Cleveland Shale of Ohio,
      U.S.A. and that of Kettle Point, Ontario, Canada.
AB  - Two permineralized woods are described in this paper, one from the Late Devonian
      Cleveland Shale of Ohio, USA and the other from the Late Devonian Huron Shale of
      Kettle Point, Ontario, Canada. Both samples of wood are satisfactorily preserved
      with primary and secondary xylem but without cortex and bark. Both are identified
      as Callixylon. They differ in specific characters from each other and from other
      described species. Hence two new species are designated, Callixylon beckii and
      Callixylon huronensis, respectively, to accommodate them in the class
      Progymnospermopsida (Progymnospermophyta) under the group Archaeopteridales.

PMID- 11295168
TI  - Aged rat hearts are not more susceptible to ischemia-reperfusion injury in vivo:
      role of glutathione.
AB  - The current study tested the hypothesis that ischemia-reperfusion (I-R) can cause
      more severe myocardial dysfunction and oxidative damage in senescent rats than
      young adult rats. Male Fischer 344 rats at the age of 6 (adult) and 24 (old)
      months were subjected to an open-chest heart surgery and randomly assigned to one
      of the following treatments: ischemia only (I), with the occlusion of the main
      descending branch of the left coronary artery (LCA) for 30 min; I-R, with the
      release of LCA occlusion for 20 min; or sham (S) operation. Heart mechanical
      performance was monitored using a fluid-filled catheter inserted in the right
      carotid artery and advanced to the left ventricle. Ischemia caused similar
      reductions of left ventricle systolic pressure (LVSP) and contractility (+/
      dP/dt) in adult and aged hearts. After I-R, adult hearts regained 82% (P<0.05) of
      the pre-ischemic LVSP, whereas the aged hearts regained 91% (P>0.05) of LVSP.
      There was no significant difference in the reduction of +/-dP/dt with I-R between
      adult and aged hearts. Old rats had lower pre-ischemic heart rate than adult
      rats, however, I-R caused no reduction of heart rate, and a smaller reduction of
      pressure-rate double product in the aged rats (10%, P>0.05) than the adult rats
      (23%, P<0.01). Aged rats demonstrated greater myocardial and plasma glutathione
      (GSH) concentrations prior to surgery, and maintained higher GSH levels and
      GSH:glutathione disulfide (GSSG) ratio with I-R. Aged hearts also had higher GSH
      peroxidase, GSH reductase and GSH sulfur-transferase activities than adult
      hearts, while I-R induced lipid peroxidation was similar. It is concluded that
      senescent hearts with intact circulatory and neural inputs are not more
      susceptible to I-R injury than adult hearts during myocardial I-R, partly because
      they have a greater GSH antioxidant protection.

PMID- 11295169
TI  - Endothelin-1 receptors on cultured rat articular chondrocytes: regulation by age,
      growth factors, and cytokines, and effect on cAMP production.
AB  - The presence of endothelin-1 receptor proteins and the expression of their
      specific mRNAs were studied using 1st passage confluent monolayers of articular
      chondrocytes, isolated from 1-month and 18-month-old rats following 24-h
      incubation with several growth factors and cytokines. The ET-1- binding sites
      were predominantly of ETA subtype since BQ123, but not IRL1038 (ETB receptor
      subtype agonist), effectively blocked 125I-ET-1 binding. The 18-month-old rat
      cell monolayers bear approximately twice as many 125I-ET-1-binding sites as the 1
      month-old rat cells. PDGF, EGF, and IGF-1 increased the number of binding sites
      in a concentration-dependent manner in both old and young rat cells with PDGF
      being the most active and EGF more active than IGF-1. IL-1beta, more potently
      than LPS, increased the number of binding sites in young rat cells only, whereas
      b-FGF, TGF-beta and GM-CSF had no effect or decreased slightly 125I-ET-1 binding
      in both types of cells. TNF-alpha strongly decreased the number of binding sites
      on both young and old rat cells, only. RT-PCR showed an increased expression of
      the specific ETA mRNA with the age of animals and in the presence of 50 ng/ml
      PDGF BB only. The incubation of the cells with ETs 1-3 for 10 min resulted in a
      50% decrease of cellular cAMP but the blocking of the receptors with BQ123 prior
      to their exposure to ETs had no effect on cAMP production whereas IRL1038
      counteracted this effect only marginally. This suggests a receptor-independent
      mechanism for ETs-induced inhibition of cAMP production. However, a 10-min co
      incubation of cells with ET-1 and with one of the following agents: cholera
      toxin, pertussis toxin, indomethacin, L-NMA, U73122 and calphostin resulted in an
      almost complete (calphostin) or partial suppression of ET-1-induced inhibition of
      cAMP production. The significance of these findings is unclear but the increased
      density of ET-1 binding sites on old rat cells and its regulation by certain
      growth factors or cytokines suggest the involvement of ET-1 in aging and possibly
      in age-related diseases.

PMID- 11295170
TI  - Aging and glucose transporter plasticity in response to hypobaric hypoxia.
AB  - In order to gain a better understanding of tissue plasticity with aging, we
      investigated the adaptive responses of young and adult animals to both 7 and 28
      days of hypobaric hypoxia. Senescence is associated with a decreased tolerance to
      hypoxia that may be related to an age-associated decline in glucose transporter
      system plasticity. In addition, elucidation of the factors contributing to the
      decreased hypoxia tolerance with aging may provide insights into ischemia for
      older individuals. Following 7 days of hypobaric hypoxia, soleus and plantaris
      muscle Glut-4 contents were increased 23-45% with a greater increase in the
      soleus muscle for both ages. A parallel decline in insulin receptor content was
      observed in both the young (soleus 56%; plantaris 74%) and adult (soleus 26%;
      plantaris 37%) animals over 7 days. Similar responses were observed in cardiac
      muscle over 7 days, with increases in content for both Glut-4 (young 25%; adult
      23%) and Glut-1 (young 33%; adult 44%) and a decline in insulin receptor (young
      27%; adult 15%). Following 28 days of hypobaric hypoxia, adult soleus, and both
      age groups plantaris muscle Glut-4 and insulin receptor contents were similar to
      control. However, the young soleus muscle Glut-4 and insulin receptor contents
      were still significantly different from control but only altered about half as
      much as following 7 days of exposure to hypobaric hypoxia. In contrast to what
      was observed for skeletal muscle, cardiac Glut-4 content was further elevated in
      both young (33%) and adult (44%) animals with longer exposure to hypobaric
      hypoxia. The young animals also showed a further decrease in heart insulin
      receptor content, while the adult did not. Interestingly, cardiac Glut-1 levels
      returned to normal values for both young and adult animals with prolonged
      exposure. An adaptive coregulation of Glut-4 and insulin receptor content appears
      to optimize the use of glucose during chronic hypobaric hypoxia within these
      tissues. Differences are apparent in the magnitude and time course of the
      response between young and adult animals.

PMID- 11295171
TI  - A new murine oxidative stress model associated with senescence.
AB  - A murine oxidative stress model was established via ozone inhalation, which was
      identified by detection of the response of antioxidant defense system, levels of
      oxidative products and effects of natural antioxidants on this model. Male BALB/c
      mice were exposed to 1.2 mg/m(3) ozone for 10 h per day. The control group was
      exposed to flowing air. From inhaling ozone, mice were killed at day 5, 10, 15
      and 20, respectively. Exposure to ozone made mice show the increase of
      malondialdehyde (MDA) contents in heart, kidney and liver, as well as 8-OHdG
      levels in urine, and resulted in cytological nuclear concentration in brain
      neurons or thymocytes. Ozone exposure also impaired antioxidative capacity such
      as the decrease of total antioxidation capacity (TAC) in sera, reduced
      glutathione (GSH) in sera or thymus and glutathione-S-transferase (GST) activity
      in spleen or thymus but not in liver. Correlation analysis showed the significant
      inverse correlation (r=-0.894, P<0.05) between thymus weight index and inhalation
      doses of ozone. Meanwhile, thymocyte in model mice proliferated more poorly than
      normal controls. Catechin and clove extract could reverse parts of changes above
      induced by ozone inhalation. These results suggest that exposure to ozone can
      result in an increased production of reactive oxygen species in vivo, which
      causes oxidative stress. The mice under oxidative stress showed senescence
      related alterations in physiological parameters as well. Taken together, our data
      demonstrates that an oxidative stress model in mice has been successfully
      established by ozone inhalation, which would be helpful to probe the relationship
      between oxidative stress and senescence and evaluate effects of antioxidants.

PMID- 11295172
TI  - Effects of age and strain on small intestinal and hepatic antioxidant defense
      enzymes in Wistar and Fisher 344 rats.
AB  - Age- and strain-associated alterations in intestinal and hepatic antioxidant
      defense enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH
      PX), and glutathione-S-transferase (GST), and lipid peroxidation were examined in
      Wistar and F344 rats of both strains aged 2 weeks, 2.5, 10 and 23 months. In the
      small intestine, activities of SOD and GSH-PX and lipid peroxidation were not
      affected by age or strain difference. Intestinal GST activity was noticeably
      increased with age in both strains, but somewhat different pattern of age-related
      changes occurred between two strains. Wistar rats aged 23 months had a
      significantly higher intestinal GST activity than corresponding age of F344 rats.
      In the liver, cytosolic SOD activity was not affected by age and strain, whereas
      GSH-PX and GST activities and lipid peroxidation were markedly influenced by age
      or strain difference. In particular, hepatic GSH-PX in Wistar rats resulted in a
      significant increase after 10 months of age and stayed at this level till 23
      months of age we examined. Also, Wistar rats showed a higher lipid peroxidation
      in the liver of 2.5 months old when compared with corresponding age of F344 rats.
      However, F344 rats did not show any significant age-dependent changes in GSH-PX
      and lipid peroxidation. In contrast, the GST activity did show much of an age
      associated alteration in both strains. Age-associated change in GST activity of
      Wistar rats was much greater than that observed in F344 rats, especially late in
      the lifetime (23 months old). It is concluded from our results that age has
      profound impact on development of some antioxidant enzymes in the small intestine
      and liver and also strain-related difference in development of antioxidant
      defense system was observed at least some time of rat life.

PMID- 11295173
TI  - The CRK3 protein kinase is essential for cell cycle progression of Leishmania
      mexicana.
AB  - The Leishmania mexicana CRK3 gene encodes a cdc2-related protein kinase with
      activity towards histone H1. Attempts to disrupt both alleles of CRK3 in the
      promastigote life-cycle stage resulted in changes in cell ploidy, which were
      avoided only when an extra copy of CRK3 was expressed from an episome. This
      provides strong evidence that CRK3 is essential to L. mexicana. The cyclin
      dependent kinase specific inhibitor flavopiridol inhibited affinity purified
      histidine tagged CRK3 (CRK3his) with an IC(50) value of 100 nM and inhibited in
      vitro growth of L. mexicana promastigotes. Incubation of promastigotes with 2.5
      microM flavopiridol for 24 h led to cell cycle arrest with an accumulation of 95%
      of cells in G2 or early mitosis (G2/M). Release from cell cycle arrest resulted
      in a semi-synchronous re-entry into the cell cycle; samples taken at 2, 4, and 6
      h after release from the block were enriched for cells in G1 (68%), S-phase
      (70%), and G2/M phase (61%), respectively. This method of synchronisation was
      used to show that the majority of CRK3his activity towards the substrate histone
      H1 was present at G2/M. These data suggest that CRK3 has an essential role in
      controlling cell cycle progression at the G2/M-phase transition in L. mexicana
      promastigotes.

PMID- 11295175
TI  - Cell cycle expression of histone genes in Trypanosoma cruzi.
AB  - In yeast and mammalian cells, the cell cycle-dependent histone genes are
      typically expressed at a 15- to 35-fold higher level during S phase than during
      other phases of the cell cycle due to increases in both their transcription rates
      (three- to 17-fold) and the stabilities of their mRNAs (three to fivefold). In
      the protozoan trypanosomatids, most life cycle stage-specific genes are not
      regulated by changes in transcription rates, but are controlled entirely by post
      transcriptional events. In contrast, little is known about cell cycle-dependent
      regulation of trypanosomatid genes. To examine cell cycle-associated expression
      of histone genes in a trypanosomatid, Trypanosoma cruzi epimastigotes were
      synchronized with hydroxyurea. The steady state levels of histone mRNAs in the
      G1, S and G2 phases of the cell cycle were found to vary only two- to fourfold,
      peaking in S phase. Nuclear run on assays showed that the histone genes are
      transcribed by RNA polymerase II and that their transcription rates do not
      increase in S phase relative to G1 and G2. Thus, during S phase of T. cruzi the
      increase in histone mRNA stability is about the same as in mammals and yeast, but
      no corresponding increase in the transcription rates of the histone genes occurs.

PMID- 11295174
TI  - Pteridine salvage throughout the Leishmania infectious cycle: implications for
      antifolate chemotherapy.
AB  - Protozoan parasites of the trypanosomatid genus Leishmania are pteridine
      auxotrophs, and have evolved an elaborate and versatile pteridine salvage network
      capable of accumulating and reducing pteridines. This includes biopterin and
      folate transporters (BT1 and FT1), pteridine reductase (PTR1), and dihydrofolate
      reductase-thymidylate synthase (DHFR-TS). Notably, PTR1 is a novel alternative
      pteridine reductase whose activity is resistant to inhibition by standard
      antifolates. In cultured promastigote parasites, PTR1 can function as a metabolic
      by-pass under conditions of DHFR inhibition and thus reduce the efficacy of
      chemotherapy. To test whether pteridine salvage occurred in the infectious stage
      of the parasite, we examined several pathogenic species of Leishmania and the
      disease-causing amastigote stage that resides within human macrophages. To
      accomplish this we developed a new sensitive HPLC-based assay for PTR1 activity.
      These studies established the existence of the pteridine salvage pathway
      throughout the infectious cycle of Leishmania, including amastigotes. In general,
      activities were not well correlated with RNA transcript levels, suggesting the
      occurrence of at least two different modes of post-transcriptional regulation.
      Thus, pteridine salvage by amastigotes may account for the clinical inefficacy of
      antifolates against leishmaniasis, and ultimately provide insights into how this
      may be overcome in the future.

PMID- 11295176
TI  - Functional analysis of leucine aminopeptidase in Caenorhabditis elegans.
AB  - To investigate the function of the enzyme leucine aminopeptidase in nematodes, a
      Caenorhabditis elegans leucine aminopeptidase gene identified in the genome
      sequence was functionally analysed by transfection of a leucine aminopeptidase
      beta-galactosidase reporter construct and characterisation of a null mutant. The
      leucine aminopeptidase transgene is expressed along the length of the gut, and
      immunolocalisation shows the enzyme in the buccal cavity, pharynx, anterior gut
      and rectum. It is constitutively expressed as seen by analysis of cDNAs
      constructed from mRNAs of nematodes taken at 2 h intervals through the life
      cycle; and by western blot analysis of protein from the same set of nematodes.
      Leucine aminopeptidase null mutants had a slower growth rate and delayed onset of
      egg-laying. We suggest that in C. elegans, leucine aminopeptidase is a digestive
      enzyme.

PMID- 11295177
TI  - Temporal co-ordination of macroschizont and merozoite gene expression during
      stage differentiation of Theileria annulata.
AB  - The bovine parasite, Theileria annulata has a complex life-cycle involving the
      expression and repression of genes during development of its morphologically
      distinct life-cycle stages. In order to detail the molecular events that occur
      during differentiation of the intracellular multinucleate macroschizont to the
      extra-cellular uninucleate merozoite, we have isolated two genes, Tash1 and Tash2
      which are differentially expressed during differentiation. Nuclear run on data
      show that Tash1 gene expression is controlled, at least in part, at the level of
      transcription. Immunofluorescence data identify the macroschizont as the location
      for both Tash1 and Tash2 gene products. Northern blot analysis of these genes
      indicated that their mRNA levels decrease during differentiation in vitro, at a
      time point coincident with major elevation in the mRNA levels of the merozoite
      antigen, Tams1, shown previously to be associated with commitment to merozoite
      production. Furthermore, experiments where cultures were incubated at 41 degrees
      C for 4 days and replaced at 37 degrees C for 2 days demonstrated that re
      expression of Tash1 occurred and is probably linked to reversion to the
      macroschizont and decreased expression of Tams1. These results imply that the
      control of macroschizont and merozoite gene expression during differentiation is
      closely co-ordinated temporally. In addition, a comparison of Tash2 and Tams1
      expression has indicated that translational or post-translational control of gene
      expression may operate in the undifferentiated macroschizont.

PMID- 11295178
TI  - Kinetic properties of dihydrofolate reductase from wild-type and mutant
      Plasmodium vivax expressed in Escherichia coli.
AB  - Antifolate drugs inhibit malarial dihydrofolate reductase (DHFR). In Plasmodium
      falciparum, antifolate resistance has been associated with point mutations in the
      gene encoding DHFR. Recently, mutations at homologous positions have been
      observed in the P. vivax gene. Since P. vivax cannot be propagated in a
      continuous in vitro culture for drug sensitivity assays, the kinetic properties
      of DHFR were studied by expression of the DHFR domain in Escherichia coli.
      Induced expression yielded a protein product that precipitated as an inclusion
      body in E. coli. The soluble, active DHFR recovered after denaturation and
      renaturation was purified to homogeneity by affinity chromatography. Kinetic
      properties of the recombinant P. vivax DHFR showed that the wild-type DHFR (Ser
      58 and Ser-117) and double mutant DHFR (Arg-58 and Asn-117) have similar K(m)
      values for dihydrofolate and NADPH. Antifolate drugs (pyrimethamine, cycloguanil,
      trimethoprim, and methotrexate), but not proguanil (parent compound of
      cycloguanil) inhibit DHFR activity, as expected. The kinetics of enzyme
      inhibition indicated that point mutations (Ser58Arg and Ser117Asn) are associated
      with lower affinity between the mutant enzyme and pyrimethamine and cycloguanil,
      which may be the origin of antifolate resistance.

PMID- 11295180
TI  - Identification and characterization of a Plasmodium falciparum RNA polymerase
      gene with similarity to mitochondrial RNA polymerases.
AB  - Nearly all mitochondrial RNA polymerase genes identified to date are encoded in
      the nucleus and have similarities to T3 and T7 bacteriophage RNA polymerases.
      Some chloroplast genes are also transcribed by T3/T7 phage-like RNA polymerases,
      raising the possibility that the apicomplexan parasites, which have both a
      mitochondrion and a plastid, might have two such genes. As part of an
      investigation of Plasmodium falciparum organelle transcription, we initiated a
      search for T3/T7 bacteriophage-like RNA polymerase genes. We employed degenerate
      primers based on highly conserved plant, animal and fungal mitochondrial RNA
      polymerase sequences to amplify corresponding P. falciparum sequences by
      polymerase chain reaction (PCR). Less well-conserved flanking sequences were
      obtained by inverse PCR. The resulting sequence predicts a 1503 amino acid open
      reading frame with similarity to other T3/T7 phage-like RNA polymerases.
      Essential amino acids that have been identified in T7 mutant analyses are
      conserved in the P. falciparum RNA polymerase gene. Comparison of the sequence
      with preliminary data from the P. falciparum genome sequencing project revealed
      strain heterogeneity within two regions of the gene. The amino-terminal predicted
      amino acid sequence of the RNA polymerase gene has similarities to mitochondrial
      targeting sequences. Taken together, these points suggest that we have identified
      the P. falciparum mitochondrial RNA polymerase gene.

PMID- 11295181
TI  - Gene targeting in the rodent malaria parasite Plasmodium yoelii.
AB  - It is anticipated that the sequencing of Plasmodium falciparum genome will soon
      be completed. Rodent models of malaria infection and stable transformation
      systems provide powerful means of using this information to study gene function
      in vivo. To date, gene targeting has only been developed for one rodent malaria
      species, Plasmodium berghei. Another rodent species, Plasmodium yoelii, however,
      is favored to study the mechanisms of protective immunity to the pre-erythrocytic
      stages of infection and vaccine development. In addition, it offers the
      opportunity to investigate unique aspects of pathogenesis of blood stage
      infection. Here, we report on the stable transfection and gene targeting of P.
      yoelii. Purified late blood stage schizonts were used as targets for
      electroporation with a plasmid that contains a pyrimethamine-resistant form of
      the P. berghei dihydrofolate reductase-thymidylate synthase (Pbdhfr-ts) fused to
      green fluorescent protein (gfp) gene. After drug selection, fluorescent parasites
      contained intact, non-rearranged plasmids that remain stable under drug-pressure.
      In addition, we used another dhfr-ts/gfp based plasmid to disrupt the P. yoelii
      trap (thrombospondin-related anonymous protein) locus by site-specific
      integration. The phenotype of P. yoelii TRAP knockout was identical to that
      previously reported for the P. berghei TRAP knockout. In the absence of TRAP, the
      erythrocytic cycle, gametocyte and oocyst development of the mutant parasites
      were indistinguishable from wild type (WT). Although the sporozoites appeared
      morphologically normal, they failed to glide and to invade the salivary glands of
      mosquitoes.

PMID- 11295182
TI  - Polymorphism in the gene encoding the apical membrane antigen-1 (AMA-1) of
      Plasmodium falciparum. X. Asembo Bay Cohort Project.
AB  - We have investigated the genetic diversity of the gene encoding the apical
      membrane antigen-1 (AMA-1) in natural populations of Plasmodium falciparum from
      western Kenya and compared it with parasite populations from other geographic
      regions. A total of 28 complete sequences from Kenya, Thailand, India, and
      Venezuela field isolates were obtained. The genetic polymorphism is not evenly
      distributed across the gene, which is in agreement with the pattern reported in
      earlier studies. The alleles from Kenya exhibit 20 and 30% more polymorphism than
      that found in Southeast Asia and Venezuelan alleles, respectively. Based on the
      gene genealogies derived from sequencing data, no evidence for allele families
      was found. We have found evidence supporting limited gene flow between the
      parasite populations, specifically, between the Southeast Asian and Venezuelan
      isolates; however, no alleles could be linked to a specific geographic region.
      This study reveals that positive natural selection is an important factor in the
      maintenance of genetic diversity for AMA-1. We did not find conclusive evidence
      indicating intragenic recombination is important in the generation of the AMA-1
      allelic diversity. The study provides information on the genetic diversity of the
      AMA-1 gene that would be useful in vaccine development and testing, as well as in
      assessing factors that are involved in the generation and maintenance of the
      genetic diversity in P. falciparum.

PMID- 11295183
TI  - Cloning and characterization of the subunits comprising the catalytic core of the
      Trypanosoma brucei mitochondrial ATP synthase.
AB  - The Trypanosoma brucei mitochondrial F(1)-ATPase has been previously isolated and
      characterized. It is composed of five subunits of molecular weights 55000, 42000,
      32000, 22000, and 17000 [1]. We have identified the alpha and beta subunits of
      the T. brucei F(1)-ATPase by N-terminal sequence determination together with
      analysis of cDNA and genomic clones. The genes for both subunits are homologous
      to the same subunits from other organisms. They contain the Walker A and B boxes
      of homology and a putative mitochondrial import sequence. The isolated T. brucei
      alpha subunit is unusually small at 42 kDa. The alpha cDNA clone encodes a
      protein of predicted size 59 kDa with a mitochondrial import presequence at the N
      terminus. The predicted size was confirmed by expression of a 59 kDa protein from
      the cDNA clone in vitro. These results suggest that the alpha subunit may have an
      unusually large mitochondrial presequence of 159 amino acids. In contrast, the
      estimated size of the native beta subunit (55 kDa) correlates well with the size
      predicted from the cDNA clone, 57 kDa, from which a 21 amino acid presequence has
      been removed in vivo. The size of the beta subunit was confirmed by expression in
      an in vitro and an Escherichia coli expression system. The purified recombinant
      beta subunit, like the native F(1)-ATPase, can be labeled by the photoaffinity
      nucleotide analogue 8-azido ATP. Binding of the 8-azido ATP probe is best
      competed by the natural substrate ATP, and is significantly reduced by
      pretreatment with the inhibitor 7-chloro-4-nitrobenzo-2-oxa-1,3-diazide as has
      been shown with beta subunits of other organisms. The differential binding of
      this photoaffinity analogue was used to resolve the identities of the alpha and
      beta subunits of the ATP synthase from T. brucei. These results are in contrast
      to results previously obtained for a related trypanosomatid Crithidia
      fasciculata.

PMID- 11295179
TI  - Gene discovery in Plasmodium chabaudi by genome survey sequencing.
AB  - The first genome survey sequencing of the rodent malaria parasite Plasmodium
      chabaudi is presented here. In 766 sequences, 131 putative gene sequences have
      been identified by sequence similarity database searches. Further, 7 potential
      gene families, four of which have not previously been described, were discovered.
      These genes may be important in understanding the biology of malaria, as well as
      offering potential new drug targets. We have also identified a number of
      candidate minisatellite sequences that could be helpful in genetic studies.
      Genome survey sequencing in P. chabaudi is a productive strategy in further
      developing this in vivo model of malaria, in the context of the malaria genome
      projects.

PMID- 11295184
TI  - Isolation and functional analysis of two thioredoxin peroxidases (peroxiredoxins)
      from Plasmodium falciparum.

PMID- 11295185
TI  - Optimized expression of green fluorescent protein in Toxoplasma gondii using
      thermostable green fluorescent protein mutants.

PMID- 11295186
TI  - Conservation of the LD1 region in Leishmania includes DNA implicated in LD1
      amplification.

PMID- 11295187
TI  - Polykinetoplast DNA structure in Dimastigella trypaniformis and Dimastigella
      mimosa (Kinetoplastida).

PMID- 11295188
TI  - Aldolase genes of Plasmodium species.

PMID- 11295189
TI  - Stevor transcripts from Plasmodium falciparum gametocytes encode truncated
      polypeptides.

PMID- 11295191
TI  - Presence of three distinct ookinete surface protein genes, Pos25, Pos28-1, and
      Pos28-2, in Plasmodium ovale.

PMID- 11295190
TI  - A survey of the Leishmania major Friedlin strain V1 genome by shotgun sequencing:
      a resource for DNA microarrays and expression profiling.

PMID- 11295192
TI  - Thin layer chromatographic determination of organic acids for rapid
      identification of bifidobacteria at genus level.
AB  - This study presents a simple and fast method for the identification of
      bifidobacteria using a thin layer chromatographic (TLC) analysis of the short
      chain fatty acids in a culture broth. When the chromatogram was sprayed with the
      indicator solution (methyl red-bromophenol blue in 70% ethanol), lactic acid
      exhibited two red spots, and acetic acid, propionic acid, and butyric acid all
      produced blue spots. Succinic acid and citric acid produced yellow and dark
      yellow spot, respectively. In addition, these organic acids showed different R(f)
      values. The total time taken to analyze the organic acids in the 10 bacterial
      culture broths using the proposed method was approximately 50 min. The proposed
      TLC method was used to analyze the organic acids in culture broths of the
      following strains, five Bifidobacterium species. (Bifidobacterium longum, B.
      breve, B. infantis, B. bifidum, and B. adolescentis) and five other lactic acid
      bacteria strains (Lactobacillus casei, L. bulgaricus, L. acidophilus,
      Streptococcus thermophilus, and S. lactis). Both spots of lactic acid and acetic
      acid were detected on all the TLC plates from the five bifidobacterial culture
      broths. The five other lactic acid bacterial culture broths, however, only
      exhibited lactic acid spots. Accordingly, the proposed TLC method would appear to
      be a useful tool for rapid identification of Bifidobacterium spp. at the genus
      level.

PMID- 11295193
TI  - A strategy for optimizing quality and quantity of DNA extracted from soil.
AB  - The efficiency of a bead beating method was studied in detail with regard to a
      variety of factors including beating time and speed, volume and temperature of
      the buffer, as well as amount and type of beads employed. The results presented
      here reveal that all of these parameters have a significant effect on yield and
      quality of DNA extracted from soils. Precise adjustment of extraction conditions
      allows for significantly higher yields of high quality DNA from soils than
      previously reported. We further evaluated the effect of the extraction conditions
      on the apparent soil microbial community structures, as observed by polymerase
      chain reaction (PCR) and RFLP. Differences in the fingerprints of DNA extracted
      under different conditions suggest that results could be biased when using gentle
      extraction procedures. Based on multiple subsequent extractions using very harsh
      extraction conditions, we propose a protocol for the quantification of the total
      DNA content in soils. Extractions from six soils of different texture and
      chemical characteristics with selected bead beating protocols revealed that the
      quality (fragment size and purity) of the extracted DNA was generally very good,
      but also depended on the soil characteristics. While a single, general protocol
      for optimal DNA recovery from all soils cannot be given, this study provides
      detailed guidelines on how to optimize the general method to obtain optimal DNA
      from individual soils.

PMID- 11295194
TI  - A simple titration method for determining Chlamydia infectivity using an image
      analyzing system.
AB  - In the biological study of Chlamydia, it is very important to determine the
      infectivity titer of the organism. For many years researchers used the serial
      dilution method to determine this titer. This method consists of diluting the
      material to be examined, inoculating suitable dilutions into susceptible cell
      cultures and cultivating them. The number of inclusions formed in host cells can
      be calculated with the naked eye under a microscope. The precision and accuracy
      of this method, however, depend on the number of inclusions per field and the
      number of fields counted. In this report, we present a simple and rapid method
      for counting a large number of inclusions using an image analysis system and an
      appropriate number of samples, and propose a sampling method based on a
      statistical analysis of the data obtained with 84 microscopic fields.

PMID- 11295195
TI  - Rapid detection, identification, and enumeration of Escherichia coli by
      fluorescence in situ hybridization using an array scanner.
AB  - A new fluorescence in situ hybridization (FISH) method using peptide nucleic acid
      (PNA) probes and an array scanner for rapid detection, identification, and
      enumeration of Escherichia coli is described. The test utilizes Cy3-labeled
      peptide nucleic acid (PNA) probes complementary to a specific 16S rRNA sequence
      of E. coli. Samples were filtered and incubated for 5 h, the membrane filters
      were then analyzed by fluorescence in situ hybridization and results were
      visualized with an array scanner. Results were provided as fluorescent spots
      representing E. coli microcolonies on the membrane filter surface. The number of
      fluorescent spots correlated to standard colony counts up to 100 colony-forming
      units per membrane filter. Above this level, better accuracy was obtained with
      PNA FISH due to the ability of the scanner to resolve neighboring microcolonies,
      which were not distinguishable as individual colonies once they were visible by
      eye.

PMID- 11295196
TI  - Rapid diagnosis of tuberculosis by detection of mycobacterial lipoarabinomannan
      in urine.
AB  - There is an urgent need for improved tools for laboratory diagnosis of active
      tuberculosis (TB). Here, we describe two methods, a catch-up ELISA and a dipstick
      test based on the detection in urine of lipoarabinomannan (LAM). LAM is a major
      and specific glycolipid component of the outer mycobacterial cell wall.
      Preliminary experiments showed that LAM is excreted in the urine of mice injected
      intraperitoneally with a crude cell wall preparation of Mycobacterium
      tuberculosis. Both methods were highly sensitive, detecting LAM at concentrations
      of 1 ng/ml and 5 pg/ml, respectively. Of 15 patients with active TB, all showed
      intermediate to high levels of LAM in their urine (absorbance values from 0.3 to
      1.2, mean 0.74). Only one sample showed an absorbance value below the chosen cut
      off value of 0.4. All but one of the urine samples from 26 healthy nursing
      workers exhibited OD value below 0.4 cut off. These methods may prove valuable
      for rapid and simple diagnosis of TB in particular in developing countries
      lacking biosafety level 3 (BSL3) facilities.

PMID- 11295197
TI  - Analysis of fungal communities by sole carbon source utilization profiles.
AB  - A simple method for characterization of fungal communities in environmental
      samples was developed. Dilute suspensions of samples in 0.2% agar containing
      three different antibiotics were pipetted into 96-well plates (Biolog SF-N)
      containing a diverse collection of 95 different carbon sources. The plates were
      incubated for 4-12 days at 22 degrees C and the absorbance measured at 650 nm.
      Canonical variates analysis was then used to analyze the multivariate data. This
      method allowed fungal communities in rhizosphere soil of corn and soybean to be
      distinguished according to soil and plant type. Data taken at a single time
      point, which varied greatly in total absorbance of the plate, separated
      rhizosphere samples primarily by soil type. When multiple time-points were
      combined to keep the total absorbance constant, differences in substrate
      utilization patterns due to different plant types could be distinguished. The
      method was also applicable to analysis of phylloplane and compost fungal
      communities. This method is readily applied to large numbers of samples and
      should be useful for community analysis in a variety of agricultural and
      ecological studies.

PMID- 11295198
TI  - Host and pathogen interaction during vaginal infection by Trichomonas vaginalis
      and Mycoplasma hominis or Ureaplasma urealyticum.
AB  - Vaginal infections by Trichomonas vaginalis and Mycoplasma hominis have been
      shown to be associated. Since M. hominis and Ureaplasma urealyticum are similar
      pathogens, both belonging to the class of the mycoplasmata, we describe here a
      molecular study into the interdependence of U. urealyticum and T. vaginalis
      during infection. Susceptibility towards infection by U. urealyticum depends on
      genetic polymorphism in the interleukin-1 receptor antagonist (IL-1RA) gene. Now,
      we defined the relation between IL-1RA genotypes and infection by M. hominis and
      T. vaginalis. Finally, we also developed a restriction fragment length
      polymorphism (RFLP) tool for mapping variation in the T. vaginalis AP33 adhesin
      in order to define putative associations between parasite subtype and
      mycoplasmata or host. Studies using crudepellets from T. vaginalis culture broth
      clearly confirm the association between T. vaginalis and M. hominis infection.
      The association between IL-1RA genotype 2,2 and lack of U. urealyticum infection
      is corroborated as well. U. urealyticum infection and infection by T. vaginalis
      are independent. Furthermore, T. vaginalis and M. hominis infection are not
      depending on IL-1RA genotypes. Interestingly, one of the three AP33 RFLP types
      identified appeared to be associated with the absence of U. urealyticum
      infection. In conclusion, the complex interaction between bacterial and parasitic
      pathogens and the infected host is determined by genetic characteristics of host
      and microorganisms involved.

PMID- 11295199
TI  - Do we have a new standard of treatment for patients with seminoma stage IIA and
      stage IIB?

PMID- 11295200
TI  - Combination carboplatin and radiotherapy in the management of stage II testicular
      seminoma: comparison with radiotherapy treatment alone.
AB  - PURPOSE: To assess the results of treatment in 33 patients with stage IIA/B
      seminoma who were treated with carboplatin and radiotherapy (RT) between January
      1989 and December 1996. PATIENTS AND METHODS: Thirty patients received single
      course single agent carboplatin (400 mg/m2 or area under curve (AUC 7), two
      patients received two courses carboplatin, and one patient received single course
      carboplatin and etoposide, all 4-6 weeks prior to infra-diaphragmatic RT. Results
      were retrospectively compared with those obtained for 80 patients treated from
      1970 to 1998 with radiotherapy alone. RESULTS: There was minimal toxicity
      associated with the use of carboplatin prior to RT. With a median follow-up of 4
      years (range 2-70 months) 2/33 patients treated with chemotherapy and RT have
      relapsed, 5-year relapse free survival (RFS) = 96.9% (95% confidence interval
      (CI) 72.9-99.4%), and one patient has died of progressive disease, 5-year overall
      survival (OS) = 96.7%. With a median follow-up of 11.2 years (range 6 months to
      25.8 years) 15/80 patients treated with RT alone have relapsed, 5-year RFS =
      80.7% (95% CI 70.1-87.9%), including 13/61 patients treated with infra
      diaphragmatic RT, 5-year RFS = 77.9%, and 2/19 treated with additional supra
      diaphragmatic RT, 5-year RFS = 89.5% (P = 0.277). Eleven out of 80 patients have
      died, 5-year OS = 94.7%. For stage IIA, 1/14 patients treated with chemotherapy
      and RT have relapsed, 5-year RFS = 92.3%, compared with 5/34 treated with infra
      diaphragmatic RT alone 5-year, RFS = 84.9% (P = 0.527). For stage IIB, 1/19
      patients relapsed (at 69 months) following chemotherapy and RT (5-year RFS =
      100%), whereas 8/27 relapsed following infra-diaphragmatic RT alone, 5-year RFS =
      69.4% (P = 0.0595). CONCLUSION: Infradiaphragmatic RT alone cures the majority of
      patients with stage II seminoma, but the relapse rate remains high particularly
      for patients with stage IIB disease. As compared with historical controls,
      carboplatin with RT appears to reduce the relapse rate in stage II seminoma with
      minimal additional toxicity and the results approach statistical significance for
      stage IIB patients. Confirmation would require a phase III randomized comparison.

PMID- 11295201
TI  - Quality of life after radiotherapy for early-stage testicular seminoma.
AB  - BACKGROUND AND PURPOSE: Standard therapy in early-stage testicular seminoma (TS)
      includes inguinal orchiectomy followed by irradiation (XRT) of the pelvic and
      para-aortic nodes. Since this treatment is highly effective in controlling the
      disease and leads to many long survivors, the quality of life (QL) may be
      impaired by treatment-induced side-effects. The aim of this study was to provide
      a QL evaluation of patients treated with XRT after orchiectomy for TS. MATERIALS
      AND METHODS: We used a validated self-completed questionnaire based on a series
      of 44 items covering all QL fields. The items were grouped into six subscales
      with standardized scores. The questionnaire was mailed to a consecutive series of
      143 patients treated between 1961 and 1995 for TS with no evidence of disease
      after primary treatment. RESULTS: Ninety-eight questionnaires (68.5%) were
      returned and are assessable. The median age of the patients was 48 years (range,
      26-85 years) at the time of completing the questionnaire, with a median follow-up
      after completion of treatment of 123 months (range, 15-432 months). The physical
      and autonomy subscale standardized scores were > or =1 in 83 and 95% of the
      cases, respectively. Psychological problems were reported by a small percentage
      of patients, ranging from 13, who reported a depressive condition, to 16%, who
      declared feeling tense. Of the patients, 86 and 89% have regularly met relatives
      and friends. The urinary score was above the central point in 99% of the
      patients. Only 6% of the patients perceived their body image as worsened by
      treatment. The patients who were more informed about the disease and therapy had
      a better physical and psychological adjustment. CONCLUSIONS: The QL in our
      patients resulted as satisfactory, with a maintained body image and few side
      effects. The information given to the patients about their disease and its
      treatment influenced the post-treatment QL adjustment.

PMID- 11295202
TI  - Partially wedged beams improve radiotherapy treatment of urinary bladder cancer.
AB  - BACKGROUND AND PURPOSE: Partially wedged beams (PWBs) having wedge in one part of
      the field only, can be shaped using dynamic jaw intensity modulation. The
      possible clinical benefit of PWBs was tested in treatment plans for muscle
      infiltrating bladder cancer. MATERIAL AND METHODS: Three-dimensional treatment
      plans for 25 bladder cancer patients were analyzed. The originally prescribed
      standard conformal four-field box technique, which includes the use of lateral
      ordinary wedge beams, was compared to a modified conformal treatment using
      customized lateral PWBs. In these modified treatment plans, only the anterior
      parts of the two lateral beams had a wedge. To analyze the potential clinical
      benefit of treatment with PWBs, treatment plans were scored and compared using
      both physical parameters and biological dose response models. One tumour control
      probability model and two normal tissue complication probability (NTCP) models
      were applied. Different parameters for normal tissue radiation tolerance
      presented in the literature were used. RESULTS: By PWBs the dose homogeneity
      throughout the target volume was improved for all patients, reducing the average
      relative standard deviation of the target dose distribution from 2.3 to 1.8%. A
      consistent reduction in the maximum doses to surrounding normal tissue volumes
      was also found. The most notable improvement was demonstrated in the rectum where
      the volume receiving more than the prescribed tumour dose was halved. Treatment
      with PWBs would permit a target dose escalation of 2-6 Gy in several of the
      patients analyzed, without increasing the overall risk for complications. The
      number of patients suitable for dose escalation ranged from 3 to 15, depending on
      whether support from all or only one of the five applied NTCP model/parameter
      combinations were required in each case to recommend dose escalation. CONCLUSION:
      PWBs represent a simple dose conformation tool that may allow radiation dose
      escalation in the treatment of muscle-infiltrating urinary bladder tumours.

PMID- 11295203
TI  - Clinical implementation of dynamic multileaf collimation for compensated bladder
      treatments.
AB  - BACKGROUND AND PURPOSE: To describe the clinical implementation of dynamic
      multileaf collimation (DMLC). Custom compensated four-field treatments of
      carcinoma of the bladder have been used as a simple test site for the
      introduction of intensity modulated radiotherapy. MATERIALS AND METHODS:
      Compensating intensity modulations are calculated from computed tomography (CT)
      data, accounting for scattered, as well as primary radiation. Modulations are
      converted to multileaf collimator (MLC) leaf and jaw settings for dynamic
      delivery on a linear accelerator. A full dose calculation is carried out,
      accounting for dynamic leaf and jaw motion and transmission through these
      components. Before treatment, a test run of the delivery is performed and an
      absolute dose measurement made in a water or solid water phantom. Treatments are
      verified by in vivo diode measurements and real-time electronic portal imaging.
      RESULTS: Seven patients have been treated using DMLC. The technique improves dose
      homogeneity within the target volume, reducing high dose areas and compensating
      for loss of scatter at the beam edge. A typical total treatment time is 20 min.
      CONCLUSIONS: Compensated bladder treatments have proven an effective test site
      for DMLC in an extremely busy clinic.

PMID- 11295204
TI  - Assessment of target dose delivery in anal cancer using in vivo thermoluminescent
      dosimetry.
AB  - PURPOSE: To measure anal dose during external beam radiotherapy (EBRT) using in
      vivo dosimetry, to study the difference of measured from prescribed dose values,
      and to evaluate possible associations of such differences with acute and late
      skin/mucosal toxicity and anorectal function. MATERIALS: Thirty-one patients with
      localized anal carcinoma underwent in vivo measurements during the first EBRT
      session. Themoluminescent dosimeters (TLD) were placed at the center of the anal
      verge according to a localization protocol. No bolus was used. Patients received
      a median dose of 39.6 Gy (range: 36-45 Gy) by anteroposterior opposed AP/PA
      pelvic fields with 6 or 18 MV photons, followed by a median boost dose of 20 Gy
      (range: 13-24 Gy). Concomitant chemotherapy (CCT), consisting of 1-2 cycles of
      continuous infusion 5-fluorouracil (5-FU) and bolus mitomycin-C (MMC), was
      usually administered during the first weeks of the pelvic and boost EBRT courses.
      Acute and late skin/mucosal reactions were recorded according to the Radiation
      Therapy Oncology Group (RTOG) toxicity scale. Anal sphincter function was
      assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) scale. RESULTS:
      TLD anal doses differed by a mean of 5.8% (SD: 5.8) in comparison to the central
      axis prescribed dose. Differences of at least 10% and at least 15% were observed
      in eight (26%) and three (9.7%) patients, respectively. TLD doses did not
      significantly correlate with acute or late grade 2-3 skin or mucosal toxicity.
      However, patients having good-fair MSKCC anal function had a significantly
      greater mean difference in anal TLD dose (10.5%, SD: 5.9) than patients having
      excellent function (3.8%, SD: 4.6) (P = 0.004). Prescribed dose values, length of
      follow-up, and age at diagnosis did not correlate with late sphincter function.
      CONCLUSIONS: These data show that AP/PA fields using megavoltage photons deliver
      adequate dose to the anal verge. However, in about one quarter of patients
      treated with this technique the anal dose varied from the prescribed dose by at
      least 10%. The observed correlation of TLD values and late sphincter function
      suggests that direct measurement of the dose delivered to the anal verge might be
      clinically relevant.

PMID- 11295205
TI  - A comparison of multileaf collimator with conformal blocks for the boost phase of
      dose-escalated conformal prostate radiotherapy.
AB  - A multileaf collimator (MLC) is compared with conformal blocks for delivering the
      boost phase of dose-escalated conformal prostate radiotherapy. When using
      conformal blocks, the volume of rectum irradiated to 90% (V90) is lower (1.4+/
      1.3%, 1 SD) for a three-field plan with gantry angles 0 degree, 90 degrees, 270
      degrees than for a six-field plan with gantry angles 50 degrees, 90 degrees, 130
      degrees, 230 degrees, 270 degrees, 310 degrees (2.1 +/- 1.3%, P = 0.002).
      However, when using an MLC in which the leaves and wedge are oriented at right
      angles, V90 is higher (4.7 +/- 3.0%) for a three-field plan than for a six-field
      plan (2.7 +/- 1.6%, P=0.05). The larger increase in V90 for the three-field plan
      when changing from conformal blocks to MLC is mainly due to the limitation
      imposed upon the MLC orientation by the use of wedges.

PMID- 11295206
TI  - Adjuvant and salvage radiation therapy after radical prostatectomy for
      adenocarcinoma of the prostate.
AB  - PURPOSE: To evaluate the outcome of adjuvant and salvage radiotherapy (RT) after
      radical prostatectomy (RP) for clinically localized prostate cancer using
      conventional clinical end-points, and the biochemical relapse-free rate (bRFR).
      METHODS: Between 1987 and 1994, 113 node negative, hormonally naive men received
      RT 1 month to 12 years after RP. Adjuvant RT was given for positive resection
      margins and/or pT3 disease. Salvage RT was given for a persistently elevated
      prostatic specific antigen (PSA), a rising PSA, or palpable recurrence post RP.
      Clinical and biochemical endpoints determined outcome. Log-rank testing and the
      Cox proportional hazards model identified factors predictive for biochemical
      relapse free rate. RESULTS: Median follow-up after RT was 3.7 years (range 0.2-9
      years). Five-year clinical local control was 95% for patients with no palpable
      evidence of disease and 59% for those with palpable recurrence (P < 0.0001). 5
      year bRFR was 81% for adjuvant RT, 19% for salvage of biochemical recurrence, 0%
      for patients with palpable disease (P < 0.0001). Improved bRFR for adjuvant and
      salvage RT was predicted by a Gleason score < 7 vs. 7 vs. > 7 (hazard ratio 1.53;
      95% CI 0.99-2.35) and an undetectable pre-RT PSA vs. PSA < 2.0 ng/ml vs. PSA >
      2.0 ng/ml (hazard ratio 3.81; 95% CI 2.47-5.87). Seminal vesicle involvement was
      not a statistically significant independent predictor of bRFR. CONCLUSIONS: The
      most favourable bRFR was observed for adjuvant therapy. Salvage was most
      successful with a pre-RT PSA < 2.0 ng/ml, or Gleason score < 7. Few patients with
      a pre-RT PSA > 2.0 ng/ml were salvaged, and none with palpable recurrence. These
      patients require investigation of alternative salvage strategies.

PMID- 11295207
TI  - A technique for inguinal node boost using photon fields defined by asymmetric
      collimator jaws.
AB  - A technique is described for treating inguinal nodes when using radiotherapy in
      the control of pelvic malignancies. A posterior photon field treats the pelvis. A
      wider anterior photon field treats pelvis and inguinal nodes. An anterior photon
      boost to nodes is delivered using asymmetric collimator jaws moved across center
      line. Advantages of this technique include simplicity of setup and treatment (a
      single isocenter is retained, and no transmission block is needed), minimal dose
      inhomogeneity, reduced dose to femoral necks reducing the risk of femoral
      fracture, low risk of nodal underdose, and elimination of dosimetric difficulties
      inherent in electron beam boosts.

PMID- 11295208
TI  - Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume
      histograms as predictive factors.
AB  - PURPOSE: To identify clinically relevant parameters predictive of late rectal
      bleeding derived from cumulative dose-volume histograms (DVHs) of the rectum
      after conformal radiotherapy of prostate cancer. MATERIALS AND METHODS: One
      hundred and nine patients treated with 3D conformal radiotherapy between 1/1994
      and 1/1996 for localized prostate cancer (clinical stage T1-T3) were available
      for analysis. All patients received a total dose of 66 Gy/2 Gy per fraction
      (specified at the International Commission on Radiation Units and Measurements
      ICRU reference point). DVHs of the contoured rectum were analyzed by defining the
      absolute (aV) and relative (rV) rectum volume that received more than 30% (V30),
      50% (V50), 70% (V70), 80% (V80), 90% (V90) and 100% (V100) of the prescribed
      dose. Additionally, a new aspect of DVH analysis was investigated by calculation
      of the area under the DVH-curve between several dose levels (area under the curve
      (AUC)-DVH). DVH-variables were correlated with radiation side effects evaluated
      in 3-6 months intervals and graded according to the EORTC/RTOG score. The median
      follow-up was 30 months (12-60 months). RESULTS: Univariate and multivariate
      stepwise Cox-Regression analysis including age, PTV, rectum size, rV100, rV90,
      rV80, rV70, rV50 rV30 and aV30 to aV100 were calculated. Late rectal bleeding
      (EORTC/RTOG grade 2) was significantly correlated with the percentage of rectum
      volume receiving > or = 90% of the prescribed dose (rV90) (P = 0.007) and
      inversely correlated in a significant way with the size of contoured rectum (P =
      0.006) in multivariate analysis. In our series, a proportion of the rectum volume
      > or = 57% were included in the 90%-isodose (rV90 > or = 57%) in one half of the
      patients, with an actuarial incidence of 31% of late rectal bleeding at 3 years.
      In the other half of the patients, when rV90 < 57%, the 3-year actuarial
      incidence was 11% (P < 0.03). CONCLUSION: Our data demonstrate a dose-volume
      relationship at the reference dose of 60 Gy ( approximately 90% of the prescribed
      dose) with respect to late rectal toxicity. The rV90 seems to be the most useful
      and easily obtained parameter when comparing treatment plans to evaluate the risk
      of rectal morbidity.

PMID- 11295209
TI  - Effect of age on radiation-induced early changes of rat rectum. A histological
      time sequence.
AB  - BACKGROUND AND PURPOSE: Radiation treatment of the elderly (> 75 years) is often
      modified due to an assumed decrease in normal tissue tolerance in this age group.
      Since more radiobiological data concerning normal tissue toxicity as a function
      of age are needed, a histological study of age-related radiation changes of the
      rectum was performed. MATERIALS AND METHODS: The rectum of young and old female
      Wistar rats (12 and 78 weeks, respectively) was irradiated with single doses of
      22 and 39 Gy. The field size was 1.5 x 2.0 cm. The animals were sacrificed at 1,
      2, 4 and 10 weeks after treatment. To evaluate radiation damage, 12 histological
      parameters were scored in four areas of the rectum. A total radiation injury
      score was calculated. The number of proliferative epithelial cells was evaluated
      by 5-bromo-2'-deoxyuridine labeling. RESULTS: Some age-related histological
      differences were observed; especially, the incidence of ulceration and vascular
      occlusion was higher in the older group. In the low dose group of the older
      animals, 60% showed ulceration, which was 0% for the young low dose animals.
      Severe vascular changes occurred early and were more extensive in older animals
      (4 weeks) than in the younger group (10 weeks). In the area adjacent to the
      treatment field, cell proliferation increased significantly in older rats at 1
      week after 22 Gy, which did not occur in the young group. CONCLUSIONS: Discrete
      radiation-induced histological differences were observed between the rectum of
      young and old Wistar rats, especially in the development of ulceration and
      vascular changes. Although the survival of these Wistar rats in earlier studies
      was not affected by age, the impact of the observed histological differences for
      their importance in the long-term is currently being investigated.

PMID- 11295210
TI  - Radiation-induced granulocyte transmigration predicts development of delayed
      structural changes in rat intestine.
AB  - We examined whether early radiation-induced granulocyte transmigration (assessed
      by the fecal transferrin excretion ELISA assay) predicts subsequent development
      of (consequential) chronic radiation enteropathy. After accounting for the effect
      of radiation dose, transferrin excretion remained an independent predictor of
      overall tissue injury, intestinal fibrosis, and mucosal ulcers, but not TGF-beta
      immunoreactivity.

PMID- 11295211
TI  - Reduction of irradiated small bowel volume and accurate patient positioning by
      use of a bellyboard device in pelvic radiotherapy of gynecological cancer
      patients.
AB  - PURPOSE: To reduce the volume of small bowel within pelvic treatment fields for
      gynecological cancer using a bellyboard device and to determine the accuracy of
      the prone treatment position. MATERIALS AND METHODS: Fifteen consecutive patients
      with a gynecologic malignancy who were treated with postoperative pelvic
      radiotherapy were selected for this study. The volume of small bowel within the
      treatment fields was calculated for both the supine and prone treatment
      positions. The patients were treated in the prone position in a so-called
      bellyboard device. During treatment sessions electronic portal images were
      obtained. An off-line setup verification and correction protocol was used and the
      setup accuracy of the positioning in the bellyboard was determined. RESULTS: The
      average volume of small bowel within the treatment fields was 229 cm(3) and 66
      cm(3) in the supine and prone treatment, respectively, which means an average
      volume reduction in the prone position of 64% (95% CI 56-72%), as compared with
      the supine position. For the position of the patient in the field, the systematic
      error defined by the standard deviation (SD) of the mean difference per patient
      between simulation and treatment images was 1.7 mm in the lateral direction, 2.1
      mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On
      average, only 0.4 setup correction per patient was required to achieve this
      accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm,
      respectively. Standard deviations of the systematic differences between patient
      positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1
      mm in craniocaudal direction. CONCLUSIONS: Treatment of gynecological cancer
      patients in the prone position using a bellyboard reduces the volume of
      irradiated small bowel. An off-line verification and correction protocol ensures
      accurate patient positioning. Daily setup variations using the bellyboard were
      small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a
      gynecological malignancy, the use of a bellyboard is recommended.

PMID- 11295212
TI  - Bladder opacification does not significantly influence dose distribution in
      conformal radiotherapy of prostate cancer.
AB  - PURPOSE: To compare the results of treatment planning with or without bladder
      contrast during simulation of three dimensional conformal radiotherapy (3D-CRT)
      for prostate cancer (18 MV X-rays, six field arrangement), and to assess the
      potential changes in dose distribution in the target and rectal volumes. METHODS
      AND MATERIALS: Based on CT-simulation using intravenous contrast media, 3-D
      conformal treatment planning was performed in five patients. To simulate a non
      opacified bladder, the electron matrix density of the opacified bladder was
      virtually changed to water density. Two treatment plans were carried out, with
      and without bladder opacification. In each patient dose distributions were
      formally compared for both plans, and the increment in monitor units (MU) needed
      to compensate for the presence of contrast media was assessed. RESULTS: A mean
      dose variation of -0.03% (range, -0.03-0.14%) and -1.13% (range, -1.85-0%) was
      observed for the prostate and the rectum, respectively. The average mean MU
      increment without bladder contrast normalized to the case with bladder contrast
      was 0.31% +/- 0.52. CONCLUSIONS: Bladder opacification used during simulation
      does not significantly influence prostate or rectal dose distributions in
      prostate patients treated with 3D-CRT, 18 MV X-rays, and a six-beam arrangement.

PMID- 11295213
TI  - Comparison of quality assurance for performance and safety characteristics of the
      facility for Boron Neutron Capture therapy in Petten/NL with medical electron
      accelerators.
AB  - BACKGROUND AND PURPOSE: The European Council Directive on health protection
      97/43/EURATOM requires radiotherapy quality assurance programmes for performance
      and safety characteristics including acceptance and repeated tests. For Boron
      Neutron Capture therapy (BNCT) at the High Flux Reactor (HFR) in Petten/NL such a
      programme has been developed on the basis of IEC publications for medical
      electron accelerators. RESULTS: The fundamental differences of clinical dosimetry
      for medical electron accelerators and BNCT are presented and the order of
      magnitude of dose components and their stability and that of the main other
      influencing parameter 10B concentration for BNCT patient treatments. A comparison
      is given for requirements for accelerators and BNCT units indicating items which
      are not transferable, equal or additional. Preliminary results of in vivo
      measurements done with a set of 55Mn, 63Cu and 197Au activation foils for all
      single fields for the four fractions at all 15 treated patients show with < +/-
      4% up to now a worse reproducibility than the used dose monitoring systems (+/-
      1.5%) caused by influence of hair position on the foil-skull distance.
      CONCLUSIONS: Despite the more complex clinical dosimetry (because of four
      relevant dose components, partly of different linear energy transfer (LET)) BNCT
      can be regulated following the principles of quality assurance procedures for
      therapy with medical electron accelerators. The reproducibility of applied
      neutron fluence (proportional to absorbed doses) and the main safety aspects are
      equal for all teletherapy methods including BNCT.

PMID- 11295215
TI  - AAc photografted porous polycabonate films and its controlled release system.
AB  - The AAc grafted porous PC film was prepared by simultaneous UV irradiation and
      the pH sensitivity of the grafted films was investigated with the simple
      controlled release device designed by the authors. The grafted porous PC films
      showed remarkable pH sensitivity and can be reused after proper treatment.

PMID- 11295216
TI  - Preliminary evaluation of caspases-dependent apoptosis signaling pathways of free
      and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells.
AB  - The purpose of the study was to examine the role of caspases in signaling
      pathways of apoptosis induced by free doxorubicin (DOX) and HPMA copolymer-bound
      DOX (P(GFLG)-DOX) in human ovarian carcinoma cells. Sensitive A2780 and DOX
      resistant A2780/AD cells were exposed to different doses of drugs within 12, 18,
      24 and 36 h. Caspase activity, expression of genes encoding human caspases 1-10,
      Apaf-1 and bcl-2 proteins and apoptosis were studied. In sensitive cells both
      free and P(GFLG)-DOX activated caspases 3, 7 and 9. In addition, P(GFLG)-DOX
      activated caspases 6 and 8. In resistant cells apoptosis induced by free DOX
      depended on the activation of caspases 2, 7 and 9, while caspase 3 was not
      involved; this explains the low degree of apoptosis induced by free DOX in
      resistant cells. P(GFLG)-DOX triggered the additional caspases 3, 6 and 8. A more
      pronounced degree of caspase activation and apoptosis after the action of P(GFLG)
      DOX depended on the inhibition of bcl-2-encoded cellular defensive mechanisms and
      a more significant activation of Apaf-1. It was concluded that HPMA copolymer
      bound DOX induced additional caspase-dependent apoptosis signaling pathways and
      the degree of the induction was higher, which led to more pronounced apoptosis
      when compared to free DOX.

PMID- 11295217
TI  - Acoustic activation of drug delivery from polymeric micelles: effect of pulsed
      ultrasound.
AB  - The effect of a continuous wave (CW) and pulsed 20-kHz ultrasound on the
      Doxorubicin (DOX) uptake by HL-60 cells from the phosphate buffered saline
      solution (PBS) and Pluronic micellar solutions was studied. Both CW and pulsed
      ultrasound enhanced DOX uptake from PBS and Pluronic micelles. The main factor
      that effected drug uptake was ultrasound power density; however, with increasing
      power, the enhanced drug uptake was accompanied by the extensive cell sonolysis.
      For PBS, no significant effect of duration of the ultrasound pulse or inter-pulse
      interval on the drug uptake was observed. For Pluronic micelles, the uptake
      increased with increasing pulse duration in the range 0.1-2 s, overall sonication
      time being the same. For 2-s pulses, the uptake was close to that under CW
      ultrasound. There was no significant effect of the duration of the inter-pulse
      interval on the drug uptake from Pluronic micelles. The data on the effect of
      pulse duration on drug uptake suggest that the characteristic times of drug
      release from micelles and drug uptake by the cells are comparable. The results
      point to two independent mechanisms controlling acoustic activation of drug
      uptake from Pluronic micelles. Both mechanisms work in concert. The first one is
      related to the acoustically-triggered drug release from micelles that results in
      higher concentration of the free drug in the incubation medium. The second
      mechanism is based on the perturbation of cell membranes that results in the
      increased uptake of the micellar-encapsulated drug. The intracellular uptake of
      Pluronic micelles was confirmed by fluorescence microscopy.

PMID- 11295218
TI  - Novel periodontal drug delivery system for treatment of periodontitis.
AB  - A conceptually novel periodontal drug delivery system (DDS) is described that is
      intended for treatment of microbial infections associated with periodontitis. The
      DDS is a composite wafer with surface layers possessing adhesive properties,
      while the bulk layer consists of antimicrobial agents, biodegradable polymers,
      and matrix polymers. The wafers contain poly(lactic-co-glycolic acid) as the main
      bioerodible component used in the bulk layer and ethyl cellulose applied as a
      matrix polymer enabling diffusion-controlled release. Starch and other polymers
      in combination with AgNO(3) serve as coatings adhesive to the teeth. In vitro
      experiments demonstrate that the wafers are capable of zero-order release of
      antimicrobial agents such as silver nitrate, benzylpenicillin, and tetracycline,
      for over 4 weeks.

PMID- 11295219
TI  - Physically crosslinked dextran hydrogels by stereocomplex formation of lactic
      acid oligomers: degradation and protein release behavior.
AB  - Hydrogels, physically crosslinked through stereocomplex formation, were obtained
      by mixing aqueous solutions of dextran with L-lactic acid grafts and dextran with
      D-lactic acid grafts. Protein-loaded hydrogels were simply prepared by dissolving
      the protein in these dextran solutions prior to mixing. It was shown that under
      physiological conditions the gels are fully degradable. When the gels were
      exposed to an aqueous buffer solution, they first showed a swelling phase in
      which their weight increased 2-3 times due to absorption of water, followed by a
      dissolution phase. The degradation time depended on the composition of the
      hydrogel, i.e., the number of lactate grafts, the length and polydispersity of
      the grafts and the initial water content, and varied from 1 to 7 days. Most
      likely, the degradation of the stereocomplex hydrogel started with hydrolysis of
      the carbonate ester, which links the lactate graft to dextran. The gels showed a
      release of the entrapped model proteins (IgG and lysozyme) over 6 days and the
      kinetics depended on the gel characteristics, such as the polydispersity of the
      lactate grafts and the initial water content. Lysozyme was mainly released by
      Fickian diffusion, indicating that its hydrodynamic diameter is smaller than the
      hydrogel mesh size. On the other hand the release of IgG was governed by
      diffusion as well as swelling/degradation of the hydrogel. Importantly, the
      proteins were quantitatively released from the gels and with full preservation of
      the enzymatic activity of lysozyme, emphasizing the protein-friendly preparation
      method of the protein-loaded stereocomplex hydrogel.

PMID- 11295220
TI  - Improvement in the mucoadhesive properties of alginate by the covalent attachment
      of cysteine.
AB  - The purpose of the present study was to improve the mucoadhesive properties of
      alginate by the covalent attachment of cysteine. Mediated by a carbodiimide, L
      cysteine was covalently linked to the polymer. The resulting thiolated alginate
      displayed 340.4+/-74.9 micromol thiol groups per g conjugate (means+/-S.D.; n=4).
      Within 2 h the viscosity of an aqueous mucus/alginate-cysteine conjugate mixture
      pH 7.0 increased at 37 degrees C by more than 50% compared to a mucus/alginate
      mixture, indicating enlarged interactions between the mucus and the thiolated
      polymer. Tensile studies carried out on freshly excised porcine intestinal mucosa
      demonstrated a total work of adhesion (TWA) of 25.8+/-0.6 and 101.6+/-36.1 microJ
      for alginate and the alginate-cysteine conjugate, respectively (means+/-S.D.;
      n=5). The maximum detachment force (MDF) was thereby in good correlation with the
      TWA. Due to the immobilization of cysteine, the swelling velocity of the polymer
      was significantly accelerated (P<0.05). In aqueous media the alginate-cysteine
      conjugate was capable of forming inter- and/or intramolecular disulfide bonds.
      Because of this crosslinking process within the polymeric network, the cohesive
      properties of the conjugate were also improved. Tablets comprising the unmodified
      polymer disintegrated within 49+/-14.5 min, whereas tablets of thiolated alginate
      remained stable for 148.8+/-39.1 min (means+/-S.D.; n=3). These features should
      render thiolated alginate useful as excipient for various drug delivery systems
      providing an improved stability and a prolonged residence time on certain mucosal
      epithelia.

PMID- 11295221
TI  - PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-alpha
      carriers.
AB  - The aim of this study was to find an effective carrier for recombinant human
      tumor necrosis factor-alpha (rHuTNF-alpha). The influence of solvent systems
      containing poly(methoxy-polyethyleneglycol cyanoacrylate-co-n-hexadecyl
      cyanoacrylate) (PEGylated PHDCA) on the biological activity of rHuTNF-alpha was
      investigated. The PEGylated PHDCA nanoparticles loading rHuTNF-alpha were
      prepared with the double emulsion method. The influence of main experimental
      factors on the entrapment efficiency was evaluated by the Uniform Design. The
      physicochemical characteristics and in vitro release of rHuTNF-alpha from the
      nanoparticles were determined. The results showed that serum albumin such as
      human serum albumin (HSA) or bovine serum albumin (BSA) could play a protective
      action on rHuTNF-alpha in the preparation process. At > or =2.0% (w/v) HSA
      concentration, more than 85% of rHuTNF-alpha activity remained and the role of
      HSA was not affected by copolymer concentrations from 0.5 to 3.0% (w/v). The
      entrapment efficiency of the nanoparticles was about 60% and the nanoparticle
      size was about 150 nm. The nanoparticles were spherical in shape and uniform with
      the value of the zeta potential about -9 mV. The rHuTNF-alpha release from the
      nanoparticle showed an initial burst and then continued in a sustained fashion.
      The results showed that the PEGylated PHDCA nanoparticles could be an effective
      carrier for rHuTNF-alpha.

PMID- 11295222
TI  - Design of rolipram-loaded nanoparticles: comparison of two preparation methods.
AB  - The aim of the present work was to investigate the preparation of nanoparticles
      as a potential drug carrier and targeting system for the treatment of
      inflammatory bowel disease. Rolipram was chosen as the model drug to be
      incorporated within nanoparticles. Pressure homogenization-emulsification (PHE)
      with a microfluidizer or a modified spontaneous emulsification solvent diffusion
      method (SESD) were used in order to select the most appropriate preparation
      method. Poly(epsilon-caprolactone) has been used for all preparations. The drug
      loading has been optimized by varying the concentration of the drug and polymer
      in the organic phase, the surfactants (polyvinyl alcohol, sodium cholate) as well
      as the volume of the external aqueous phase. The rolipram encapsulation
      efficiency was high (>85%) with the PHE method in all cases, whereas with the
      SESD method encapsulation efficiencies were lower (<40%) when lower surfactant
      concentrations and reduced volume of aqueous phase were used. Release profiles
      were characterized by a substantial initial burst release with the PHE method (25
      35%) as well as with the SESD method (70-90%). A more controlled release was
      obtained after 2 days of dissolution with the PHE method (70-90%), no further
      significant drug release was observed with the SESD method.

PMID- 11295223
TI  - Development and characterization of a novel peroral peptide drug delivery system.
AB  - Novel drug delivery systems were developed for peroral administration of peptide
      and protein drugs for site specific mechanical fixation at the gut wall and with
      specific release patterns. These so-called shuttle systems were designed by using
      superporous hydrogels (SPH) and SPH composite (SPHC) as the conveyor of a core
      which contained the model compound N-alpha-benzoyl-L-arginine ethylester (BAEE).
      Two different types of shuttle systems were evaluated: (a) core inside the
      shuttle system, and (b) core attached to the surface of shuttle system. Each of
      these systems was made of two parts: (1) the conveyor system made of SPHC which
      is used for keeping the dosage form at specific site(s) of the GI tract by
      mechanical interaction of the dosage form with the intestinal membranes, and (2)
      the core containing the active ingredient and incorporated in the conveyor
      system. The effect of formulation composition of the core on the release profile
      of BAEE was investigated by changing the type and amount of excipients in the
      formulations. In addition, the effect of various enteric-coat layers on the
      release profile and dissolving of the dosage form was investigated. The systems
      were also characterized for trypsin inactivation and Ca(2+) binding. The release
      profile of BAEE from the core formulation consisting of PEG 6000 microparticles
      or small tablets showed the desired burst release. When these core formulations
      were incorporated into the conveyor system made of SPH and SPHC, a suitable time
      controlled release profile was obtained. Changing the type, concentration and
      thickness of the enteric-coat layer influenced the starting time of BAEE release
      from the dosage form, which indicates the necessary lag time for dissolving of
      the dosage form at any desired specific site of drug absorption in the intestine.
      Both SPH and SPHC were found to partly inhibit the activity of trypsin, due to
      two mechanisms: Ca(2+) binding and entrapment of the enzyme in these polymers. In
      conclusion, the presently developed delivery systems demonstrate suitable in
      vitro characteristics with an appropriate time-controlled release profile, making
      these systems very promising for effective peroral delivery of peptide and
      protein drugs.

PMID- 11295225
TI  - Modulation of drug release from hydrogels by using cyclodextrins: the case of
      nicardipine/beta-cyclodextrin system in crosslinked polyethylenglycol.
AB  - A simple approach is presented to modulate drug delivery from swellable systems
      by using complexants. The effect of complexants has been interpreted by means of
      simple mass balances on diffusing species and the involved relevant parameters
      have been individuated. The application of this strategy to the release of
      nicardipine (NIC) from swellable systems by using beta-cyclodextrin (CD) as
      complexant has evidenced the potential of the approach to tailor drug release.
      Crosslinked polyethyleneglycol has been synthesized, characterized and used as
      the swellable matrix. Swelling kinetics, NIC and CD diffusivities in the swollen
      matrix and NIC/CD phase solubility studies have been performed. The polymer
      matrix has been loaded with pure NIC or with NIC and CD at different ratios and
      release kinetics evaluated. Release profiles have shown that the presence of CD
      significantly affected drug delivery by decreasing the effective diffusivity of
      NIC. The higher the CD/NIC ratio the slower is the release. This effect has been
      interpreted on the basis of the proposed model and physically sound assumptions.

PMID- 11295224
TI  - In vivo assessment of enhanced topical delivery of terbinafine to human stratum
      corneum.
AB  - PURPOSE: The objective of this study was to evaluate, using attenuated total
      reflectance Fourier transform infrared spectroscopy, the stratum corneum (SC)
      bioavailability of terbinafine (TBF) following topical treatment with four
      different formulations. METHODS: Four skin sites on the ventral forearms of five
      healthy volunteers were treated for 2 h using one of four formulations based on a
      vehicle consisting of 50% ethanol and 50% isopropyl myristate. Three of these
      formulations included a percutaneous penetration enhancer: either 5% oleic acid,
      10% 2-pyrrolidone or 1% urea. The SC concentration profile of TBF was measured by
      repeated infrared spectroscopic measurements while sequentially stripping off the
      layers of this barrier membrane with adhesive tape. This method was validated by
      HPLC analysis of TBF extracted from the stripped tapes. Transepidermal water loss
      (TEWL) measurements were also performed, to permit facile estimation of SC
      thickness. RESULTS: The SC concentration profiles of TBF were fitted to the
      appropriate solution of Fick's second law of diffusion, thereby allowing
      determination of the characteristic diffusion and partitioning parameters of the
      permeating drug. This analysis enabled the efficacies of the different
      formulations tested to be compared to the no-enhancer control. While it was found
      that the formulation containing 5% oleic acid significantly enhanced the SC
      availability of TBF, the other formulations did not improve the apparent drug
      delivery. CONCLUSIONS: A facile and minimally invasive methodology to evaluate an
      important aspect of topical drug bioavailability has been described. The
      analytical methods used (infrared spectroscopy and HPLC) allow estimates of both
      relative and absolute drug bioavailability in the SC and may be useful,
      therefore, in the critical determination of bioequivalence between topical
      formulations.

PMID- 11295226
TI  - Oil components modulate physical characteristics and function of the natural oil
      emulsions as drug or gene delivery system.
AB  - Oil-in-water (o/w) type lipid emulsions were formulated by using 18 different
      natural oils and egg phosphatidylcholine (egg PC) to investigate how emulsion
      particle size and stability change with different oils. Cottonseed, linseed and
      evening primrose oils formed emulsions with very large and unstable particles.
      Squalene, light mineral oil and jojoba bean oil formed stable emulsions with
      small particles. The remaining natural oils formed moderately stable emulsions.
      Emulsions with smaller initial particle size were more stable than those with
      larger particles. The correlation between emulsion size made with different oils
      and two physical properties of the oils was also investigated. The o/w
      interfacial tension and particle size of the emulsion were inversely
      proportional. The effect of viscosity was less pronounced. To study how the oil
      component in the emulsion modulates the in vitro release characteristics of
      lipophilic drugs, three different emulsions loaded with two different drugs were
      prepared. Squalene, soybean oil and linseed oil emulsions represented the most,
      medium and the least stable systems, respectively. For the lipophilic drugs,
      release was the slowest from the most stable squalene emulsion, followed by
      soybean oil and then by linseed oil emulsions. Cationic emulsions were also
      prepared with the above three different oils as gene carriers. In vitro
      transfection activity was the highest for the most stable squalene emulsion
      followed by soybean oil and then by linseed oil emulsions. Even though the in
      vitro transfection activity of emulsions were lower than the liposome in the
      absence of serum, the activity of squalene emulsion, for instance, was ca. 30
      times higher than that of liposome in the presence of 80% (v/v) serum. In
      conclusion, the choice of oil component in o/w emulsion is important in
      formulating emulsion-based drug or gene delivery systems.

PMID- 11295228
TI  - Induction of mitochondrial heat shock protein 60 and 10 mRNAs following transient
      focal cerebral ischemia in the rat.
AB  - Heat shock proteins (HSPs) 60 and 10 are stress-inducible mitochondrial matrix
      proteins that form a chaperonin complex that is important for mitochondrial
      protein folding and function. The effect of cerebral ischemia on mitochondrial
      HSPs is unclear. The topographical and chronological patterns of HSP60 and HSP10
      messenger ribonucleic acid (mRNA) expression and induction were investigated in
      the rat focal cerebral ischemia model. Focal cerebral ischemia was produced by
      transient middle cerebral artery occlusion for 30 or 90 min. Expression of mRNAs
      was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and
      in situ hybridization. RT-PCR analysis showed that both HSP60 and HSP10 mRNA
      levels increased significantly in the ischemic cortex from 4 to 24 h of
      reperfusion after 30 min of occlusion. In situ hybridization analysis
      demonstrated significant induction of both mRNAs in the whole ischemic cortex
      after 30 min of occlusion and in the dorsomedial border (penumbra) of the
      ischemic cortex and ipsilateral hippocampus after 90 min of occlusion. Expression
      patterns and the timing of the induction of both HSP60 and HSP10 mRNAs were
      identical throughout the experiments. Simultaneous induction of the mRNAs for the
      mitochondrial chaperonins, HSP60 and HSP10, in various regions in focal cerebral
      ischemia demonstrates that mitochondrial stress conditions persist concomitantly
      with cytosolic stress conditions in focal cerebral ischemia.

PMID- 11295227
TI  - Activation of a novel microglial gene encoding a lysosomal membrane protein in
      response to neuronal apoptosis.
AB  - In an attempt to understand the molecular mechanism of microglial activation in
      response to neuronal death or degeneration, we have employed cerebellar cell
      cultures prepared from P7 rats and grown in normal K(+) (5.4 mM) medium. Under
      this condition, glial cells respond to degeneration and cell death of granule
      neurons that begins to occur at 4 days in vitro (DIV). Here we describe a novel
      gene, granule cell death-10 (gcd-10) that is expressed in microglia and up
      regulated in an early period of granule cell death. gcd-10 is homologous to the
      mouse lysosomal-associated multispanning membrane protein (LAPTm5) with
      hematopoietic origin. Immunocytochemistry and vital staining with acridine orange
      revealed that GCD-10 was localized at the perinuclear area of cultured microglia
      and COS 1 cells infected with a GCD-10-expressing adenoviral vector. In
      cerebellar cell cultures, however, GCD-10 was markedly up-regulated and widely
      distributed to the cytoplasm, which paralleled the localization of the ED1
      antigen, the lysosomal marker. In vivo, gcd-10 is expressed mainly in the brain
      and the spleen, and was up-regulated upon nerve injury in retina 7 days after
      optic nerve transection. These findings suggest that gcd-10 is involved in the
      dynamics of lysosomal membranes associated with microglial activation both in
      vitro and in vivo.

PMID- 11295229
TI  - Memory consolidation in day-old chicks requires BDNF but not NGF or NT-3; an
      antisense study.
AB  - Neurotrophins have been implicated in memory consolidation and recall as well as
      in other forms of neural plasticity. This study examined the effects of Brain
      Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF) and Neurotrophin-3
      (NT-3) on consolidation of memory for a one-trial passive avoidance task in day
      old chicks. In this task chicks, having pecked once at a bitter tasting bead,
      avoid a similar but dry bead subsequently. Intracerebral administration of
      antisense ODNs to BDNF 6-12 h prior to training induced amnesia for the avoidance
      response by 3 h after training. Administration of a "control" scrambled sequence
      or saline had no effect on recall; chicks continued to avoid the bead. Treatment
      with BDNF-AS did not inhibit shorter-term recall; amnesia was not present 1 h
      after training, but prevented longer-term recall, as amnesia was still present 24
      h after training. Treatment with BDNF-antisense reduced both BDNF mRNA and BDNF
      protein in the chick brain, but did not alter mRNA levels of glyceraldehyde-3
      phosphate dehydrogenase. By contrast, no effect of antisense to NGF or NT-3 on
      behaviour was observed, even though administration reduced the mRNA for each.
      There were no significant effects of any antisense on other behavioural measures
      at the doses used. Thus we conclude that BDNF has a specific role in memory
      consolidation for the passive avoidance task.

PMID- 11295230
TI  - Comparative distribution of voltage-gated sodium channel proteins in human brain.
AB  - Antisera directed against unique peptide regions from each of the human brain
      voltage-gated sodium channel alpha subunits were generated. In immunoblots these
      were found to be highly specific for the corresponding recombinant polypeptides
      and to recognise the native holoprotein in human brain membrane preparations.
      These antisera were used to perform a comparative immunohistochemical
      distribution analysis of all four brain sodium channel subtypes in selected human
      CNS regions. Distinct but heterogeneous distribution patterns were observed for
      each of the alpha subunits. In general, these were complimentary to that
      previously shown for the corresponding human mRNAs. A high degree of conservation
      with respect to the distribution found in rat was also evident. The human alpha
      subunit proteins exhibited distinct subcellular localisation patterns. Types I,
      III and VI immunoreactivity was predominantly in neuronal cell bodies and
      proximal processes, whereas type II was concentrated along axons. This is similar
      to rat brain and suggests the different the sodium channel subtypes have distinct
      functions which are highly conserved between human and rodents. A notable
      difference was that the type III protein was detected in all human brain regions
      examined, unlike in rat brain where expression in adults is very restricted. Also
      in contrast to rat brain, the human type VI protein was not detected in axons of
      unmyelinated neurons. These differences may reflect true species variation and
      could have important implications for understanding the function of the sodium
      channel subtypes and their roles in human disease.

PMID- 11295231
TI  - Aggravation of brain injury after transient focal ischemia in p53-deficient mice.
AB  - The transcriptional factor p53 is a regulatory protein which contributes to the
      preservation of tissue integrity by promoting either DNA repair or apoptosis. To
      establish the pathophysiological role of this protein in ischemia, we produced 1
      h transient middle cerebral artery (MCA) occlusion in normal and in p53-deficient
      mice and investigated the resulting tissue damage by multiparametric imaging.
      Possible genetic influences on the angioarchitecture of the MCA territory and
      blood flow were examined by intravascular latex infusion and laser-Doppler
      flowmetry. Wild-type (p53(+/+)), heterozygous (p53(+/-)) and homozygous (p53(-/
      )) mice deficient for the p53 gene did not differ in respect to angioarchitecture
      or the effect of vascular occlusion on blood flow and general physiological
      parameters. Twenty-four hours after 1 h MCA occlusion, mice revealed a gene dose
      dependent decline in the size of metabolic disturbances (ATP depletion and
      inhibition of protein synthesis) and histological injury (Cresyl Violet
      staining). DNA fragmentations detected by terminal deoxynucleotidyl transferase
      mediated UTP nick end labeling (TUNEL) did not differ in the three groups and
      were only present in ATP-depleted tissue. Our findings suggest that after
      transient focal brain ischemia p53 prevents rather than aggravates brain injury,
      and that this effect is brought about by mechanisms that are unrelated to the pro
      apoptotic properties of this gene.

PMID- 11295232
TI  - Norepinephrine-induced CRH and AVP gene transcription within the hypothalamus:
      differential regulation by corticosterone.
AB  - We have previously demonstrated that microinjection of norepinephrine (NE) into
      the paraventricular nucleus of the hypothalamus (PVN) of conscious rats elicits a
      marked increase in CRH gene transcription, indicated by CRH hnRNA levels, without
      changing AVP hnRNA levels. We hypothesized that this differential response is due
      to differential sensitivity of AVP and CRH gene transcription to the inhibitory
      effects of the NE-induced rise in corticosterone. In the current study, we used
      animals that had been adrenalectomized and implanted with a subcutaneous
      corticosterone pellet (ADX/B) which prevented the NE-induced rise in
      corticosterone levels. NE (50 nmol) or artificial CSF was injected into the PVN
      of conscious rats, which had undergone either sham-operation (SHAM) or ADX/B 1
      week earlier. CRH and AVP hnRNA levels were semi-quantitated by in situ
      hybridization using intron-specific riboprobes. In both SHAM and ADX/B animals,
      CRH hnRNA levels were significantly elevated at the 15 min time-point and
      returned to basal levels by 120 min. At 15 min, the magnitude of the CRH hnRNA
      response was only slightly greater in the ADX/B group than SHAM. In contrast,
      changes in medial parvocellular PVN AVP hnRNA levels in the ADX/B group were
      significantly greater than the changes observed in the SHAM group, at both the 15
      and 120 min time-points. These results suggest that corticosterone has a greater
      impact on the transcriptional regulation of AVP than CRH, suggesting important
      differences and distinct roles of these secretagogues in the regulation of the
      hypothalamic-pituitary-adrenal axis.

PMID- 11295233
TI  - Similarity and variation in gene expression among human cerebral cortical
      subregions revealed by DNA macroarrays: technical consideration of RNA expression
      profiling from postmortem samples.
AB  - The functional regionality of the human cerebral cortex suggests that a set of
      genes might be activated in each subregion of the neocortex to support its
      specific functions. To test this hypothesis, we employed the DNA array technique
      to compare the mRNA expression profiles of three neocortical subregions of the
      human brain: prefrontal cortex (Area 46), motor cortex (Area 4) and visual cortex
      (Area 17). The macroarray analysis on high quality mRNA from postmortem brains
      revealed that the expression profiles of the different cortical areas are almost
      similar: only six out of 1088 known genes exhibited significant differences (>2
      fold) in their expression. RT-PCR studies with an increased number of samples
      confirmed that expression of only two genes, annexin II and early growth response
      protein 1, varied by 2-fold among the regions, whereas expression of the others
      showed large inter-individual difference. These results suggest that the whole
      neocortex of humans is more homogeneous than we expected at the level of gross
      gene expression profiles. In parallel, sensitivity and accuracy of radioisotope
      based DNA macroarrays and fluorescence-based DNA microarrays were tested.

PMID- 11295234
TI  - The comparative analysis of proenkephalin mRNA expression induced by cholera
      toxin and pertussis toxin in primary cultured rat cortical astrocytes.
AB  - In rat astrocytes, incubation with cholera toxin (CTX; 0.1 microg/ml) for 8 h
      increased proenkephalin (proENK) mRNA level (10-fold), which was further
      increased by dexamethasone (DEX; 1 microM) (2.2-fold as much as CTX alone).
      Although pertussis toxin (PTX; 0.1 microg/ml) did not affect the basal proENK
      mRNA level, DEX significantly increased proENK mRNA level in PTX-treated cells (6
      fold). The inhibition of protein synthesis by cycloheximide (CHX; 15 microM) also
      increased proENK mRNA level in PTX-treated cells (5.2-fold), but not in CTX
      stimulated cells. The treatment with CTX, but not PTX, increased c-Fos and Fra-2
      protein levels as well as AP-1, CRE, or ENKCRE-2 DNA binding activity, but
      neither toxin affected Fra-1, c-Jun, JunB, and JunD protein levels. CHX
      significantly attenuated CTX-induced increase of c-Fos or Fra-2 protein level and
      AP-1, CRE, or ENKCRE-2 DNA binding activity, although CHX alone did not affect
      the basal AP-1, CRE, and ENKCRE-2 DNA binding activities. Phosphorylated CREB
      level was increased by both CTX and PTX, although the magnitude of
      phosphorylation of CREB by PTX was much less than that by CTX. In addition, CHX
      further or persistently increased PTX- or CTX-induced phosphorylated CREB levels
      in parallel with increases in proENK mRNA. However, DEX did not alter the basal
      or stimulated phosphorylated-CREB level. These results suggest that the elevation
      of phosphorylation of CREB rather than AP-1 level may be involved in CTX-induced
      and CHX-dependent-PTX-induced increase of proENK mRNA level. In addition, AP-1
      expression or CREB phosphorylation appears not to be involved the potentiative
      action of DEX on proENK mRNA expression in CTX- and PTX-treated astrocytes.

PMID- 11295235
TI  - Failure to sustain recovery of Na,K-ATPase function is a possible mechanism for
      striatal neurodegeneration in hypoxic-ischemic newborn piglets.
AB  - Hypoxia-ischemia (HI) in the newborn can lead to a variety of sensorimotor
      abnormalities, including movement and posture disorders. Striatal neurons undergo
      necrosis after HI in piglets, but mechanisms for this neuronal death are not
      understood. We tested the hypothesis that Na,K-ATPase is defective in striatum
      early after HI. Piglets (1 week old) were subjected to 30 min hypoxia (arterial
      oxygen saturation 30%) and then 7 min of airway occlusion (oxygen saturation 5%),
      producing asphyxic cardiac arrest. Animals were resuscitated and recovered for 3,
      6, 12, and 24 h, respectively. Neuronal necrosis in the striatum is progressive
      [14]. Na,K-ATPase activity (percent of control) was 60, 98, 51, and 54% at 3, 6,
      12, and 24 h after HI, respectively. Intrastriatal differences in enzyme activity
      were detected histochemically, with the putamen showing greater loss of Na,K
      ATPase activity than caudate after 12 h recovery. Immunoblotting showed that the
      levels of the alpha(3) isoform (localized exclusively to neurons) were 85, 115,
      101, and 79% of sham control at 3, 6, 12, and 24 h, respectively. Levels of
      beta(1), the predominant beta isoform, were similar to alpha(3), while levels of
      the alpha(1) subunit, the catalytic isoform found in neurons and glia, were 182,
      179, 226, and 153% at the same recovery times. We conclude that early
      inactivation of Na,K-ATPase function participates in the pathogenesis of striatal
      neuron necrosis, but that loss of enzyme function early after HI is not caused by
      depletion of composite alpha/beta subunits.

PMID- 11295236
TI  - Dose-dependent induction of mRNAs encoding brain-derived neurotrophic factor and
      heat-shock protein-72 after cortical spreading depression in the rat.
AB  - Previous studies have demonstrated that cortical spreading depression (CSD)
      increases the expression of putative neuroprotective proteins. The objective of
      the present study was to elucidate the relationship between the number of
      episodes of CSD and steady-state levels of mRNAs encoding brain-derived
      neurotrophic factor (BDNF), heat-shock protein-72 (hsp72) and c-fos. Wistar rats
      were administered one, five, or twenty-five episodes of CSD evoked by application
      of 2 M KCl to the frontal cortex of one hemisphere. Animals were permitted to
      recover for 30 min, 2 h or 24 h prior to sacrifice. Total RNA was isolated from
      the parietal cortex of each hemisphere and analyzed using Northern blots. At 30
      min recovery, levels of BDNF mRNA were not significantly elevated after 1 episode
      of CSD, but were increased 4-fold after five episodes of CSD and 11-fold after
      twenty-five episodes of CSD, relative to levels in the contralateral hemisphere.
      At 2 h recovery, BDNF mRNA levels increased 2-, 3- and 9-fold, respectively. At
      24 h, BDNF mRNA had returned to control levels in all groups. Thus, CSD increased
      levels of BDNF mRNA in a dose-dependent fashion at the early recovery times.
      Hsp72 mRNA was below the level of detection after 1 and 5 episodes of CSD.
      However, after twenty-five episodes of CSD, hsp72 mRNA levels were increased in
      the ipsilateral hemisphere at 30 min and 2 h recovery. Unlike levels of BDNF and
      hsp72 mRNA, levels of c-fos mRNA were increased nearly to the same extent at 30
      min and 2 h after one, five or twenty-five episodes of CSD before returning to
      control by 24 h recovery. These results demonstrate that CSD triggers a dose
      dependent increase in the expression of genes encoding neuroprotective proteins,
      which may mediate tolerance to ischemia induced by CSD.

PMID- 11295237
TI  - Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14,
      16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain.
AB  - Regulators of G-protein signaling (RGS) proteins are a novel family of GTPase
      activating proteins that interact with Galpha subunits of the Gi/o, Gz, Gq and
      G(12/13) subfamilies to dampen G-protein-coupled receptor (GPCR)-mediated
      signaling by accelerating intrinsic Galpha-GTPase activity. In the present study,
      we report on messenger ribonucleic acid (mRNA) localization in rat brain of six
      RGS genes by in situ hybridization. The distribution patterns of RGS2, RGS13,
      RGS14 and GAIP (Galpha interacting protein) overlapped in most brain regions
      examined. Highest regional expression was observed for RGS2 in the cerebral
      cortical layers, striatum, hippocampal formation, several thalamic and
      hypothalamic nuclei and hindbrain regions such as the pontine, interpeduncular
      and dorsal raphe nuclei. Levels of RGS14 mRNA closely paralleled those of RGS2
      expression levels throughout most brain regions. RGS13 mRNA was enriched in the
      hippocampal formation, amygdala, mammillary nuclei as well as the pontine and
      interpeduncular nuclei. GAIP expression levels were highest in the hippocampal
      formation with moderate to low levels present in all other regions studied. Of
      the six RGS genes probed, RGS16 mRNA displayed a discrete localization
      predominantly in the thalamic midline/intralaminar and principal relay nuclei,
      and the hypothalamic suprachiasmatic nucleus. RGS1 mRNA signal was not detected
      in brain. In conclusion, the in situ hybridization studies for RGS2, RGS13,
      RGS14, RGS16 and GAIP mRNAs extend our knowledge of the distribution of RGS genes
      expressed in the rat central nervous system, and indicate overlapping RGS
      enriched regions that may be indicative of functional diversification in GPCR
      signaling pathway modulation.

PMID- 11295238
TI  - Localization of mRNAs for six ARFs (ADP-ribosylation factors) in the brain of
      developing and adult rats and changes in the expression in the hypoglossal
      nucleus after its axotomy.
AB  - ADP-ribosylation factors (ARFs) play crucial roles in the intracellular vesicular
      transport and in regulation of phospholipid-modifying enzyme activities and
      cytoskeletons. Using in situ hybridization histochemistry, the gene expression
      for six isoforms of ARF was examined during normal development of rats and in the
      hypoglossal nucleus following its axotomy. In the embryonic brain, the expression
      for ARF-1, -4, -5, -6 mRNAs was distinct in the ventricular germinal zone while
      that for ARF-3, -4, -5 in the mantle zone. In early postnatal brain, the
      expression for six ARFs was seen widely in various loci of the gray matter with
      different intensity, and the expression of ARF-4, -5, -6 mRNAs was evident in the
      cerebellar external granule cell layer. In the adult brain, the gene expression
      for all ARF isoforms decreased more or less in most gray matters and the distinct
      expression was maintained mainly in the hippocampal and dentate neuronal layers
      and cerebellar cortex. The expression levels of ARF-2 and -4 mRNAs in affected
      hypoglossal nucleus increased after 24 h up to 7 days following axotomy of the
      hypoglossal nerve, while no such changes were seen in the expression levels for
      the other ARFs. The present findings suggest that ARFs are differentially
      involved in some processes essential to nerve regeneration as well as neuronal
      differentiation and maturation.

PMID- 11295239
TI  - Developmental changes in the expression of GABA(A) receptor subunits (alpha(1),
      alpha(2), alpha(3)) in the cat visual cortex and the effects of dark rearing.
AB  - The present study used Western blots and Northern slot blots to determine changes
      in the level of expression of GABA(A) receptor subunits alpha(1), alpha(2), and
      alpha(3), in relation to the "critical period" in cat visual cortex. Levels of
      the GABA(A) alpha(1) subunit were lowest at 1 week, increased four-fold to a
      maximum at 10 weeks, and declined slightly (35%) into adulthood. Levels of the
      GABA(A) alpha(2) and alpha(3) subunits were highest at 1 week of age, decreased
      two-fold by 10 weeks of age and were constant thereafter. Comparison between
      visual cortex from normal and dark-reared cats at 5 weeks and 20 weeks showed
      that alpha(1) and alpha(3) subunit expression was elevated in dark-reared animals
      by approximately 50% at both ages. alpha(2) expression was not affected. These
      results implicate the importance of a shift from putative immature to mature
      GABA(A) receptor subunits during the critical period of visual cortex and in
      conjunction with parallel analysis of NMDA receptor subunit maturation, further
      support the notion that a changing excitatory/inhibitory balance is critical for
      neuronal plasticity.

PMID- 11295240
TI  - Expression of the SCAMP-4 gene, a new member of the secretory carrier membrane
      protein family, is repressed by progesterone in brain regions associated with
      female sexual behavior.
AB  - Rodent female reproductive behavior is facilitated by the genomic targets of
      estrogen (E) and progesterone (P) in neuroendocrine regions of the brain. Using
      the differential display-PCR technique to identify these targets we discovered a
      novel hormone-sensitive mRNA in the female rat brain that is substantially
      reduced in the ventromedial hypothalamus (VMH) after 3 h of P treatment,
      following 24 h of E priming. Northern blots show that it is a single transcript
      of approximately 1.7 kb. The sequence of the corresponding full-length cDNA
      indicates that this gene is the rat homolog of mouse SCAMP-4, the fourth member
      identified in a family of proteins known as secretory carrier membrane proteins
      (SCAMPs). In situ hybridization studies show that SCAMP-4 mRNA is relatively low
      throughout the rat forebrain, with the highest levels observed in the VMH,
      habenula and hippocampus. The SCAMP-4 message is also less abundant in the
      habenula and VMH during proestrus, when circulating levels of E and P are at
      their peak, than during diestrus-1 when circulating hormone levels are low. Amino
      acid sequence analysis indicates that SCAMP-4 lacks the putative calcium binding
      and leucine zipper structures, as well as protein-protein interacting NPF domains
      common among most SCAMP family members, but is the only member identified to date
      to contain a putative protein kinase C (PKC) phosphorylation site. Fluorescent
      microscopy of cells transfected with a SCAMP-4/GFP fusion construct reveals
      distinct fluorescence in subcellular aggregates that may contain secretory
      vesicles. In addition to our results in the VMH, the finding of high levels of
      SCAMP-4 message in the habenula, a brain area rich in mast cells, together with
      previous reports linking mast cell secretion with courtship behavior also suggest
      a possible role for SCAMP-4 in reproductive behaviors associated with mast cell
      activity in the central nervous system (CNS).

PMID- 11295241
TI  - Presence of morphine and morphine-6-glucuronide in the marine mollusk Mytilus
      edulis ganglia determined by GC/MS and Q-TOF-MS. Starvation increases opiate
      alkaloid levels.
AB  - Morphine and morphine-6-glucuronide, a morphine metabolite, have been identified
      and quantified in Mytilus edulis pedal ganglia at a level of 2.67+/-0.44 and
      0.98+/-0.14 ng/ganglia, respectively by high performance liquid chromatography
      coupled to electrochemical detection. These opiate alkaloids were further
      identified by both gas-chromatography mass spectrometry and nanoflow electrospray
      ionization double quadrupole orthogonal acceleration Time of Flight mass
      spectrometry. In animals that were starved, the morphine level rose to 6.38+/
      0.88 ng/ganglion and the morphine 6-glucoronide rose to a level of 23.0+/-3.2
      ng/ganglion after 30 days. These studies demonstrate that opiate alkaloids are
      present as naturally occurring signal molecules whose levels respond to stress,
      i.e., starvation. Opiate alkaloids were not found in the animal's incubation
      media or food, demonstrating their synthesis occurred in the respective tissue.
      These new method of opiate alkaloid detection, conclusively proves that morphine
      and morphine-6-glucuronide are present in animal tissues.

PMID- 11295242
TI  - NMDA receptor activation enhances diazepam binding inhibitor and its mRNA
      expressions in mouse cerebral cortical neurons.
AB  - Effects of N-methyl-D-aspartate (NMDA) on diazepam binding inhibitor (DBI) and
      its mRNA expression in mouse cerebral cortical neurons were examined. A
      significant increase in DBI mRNA expression was observed 1 day after the exposure
      to 0.1 microM NMDA and the maximal expression occurred 2 days after the exposure,
      whereas transient exposure to 0.1 microM NMDA for 15 min, 1 and 3 h produced no
      changes in the expression. Similarly, no changes in the expression were found by
      the concomitant exposure to NMDA and MK-801, a NMDA receptor antagonist, for 72 h
      subsequent to the incubation with NMDA alone for 3 h. Such NMDA-induced increases
      in DBI mRNA expression were dose-dependently inhibited by MK-801. Moreover,
      neuronal DBI content significantly increased by treatment with NMDA, which was
      completely abolished by MK-801. These results indicate that continuous activation
      of NMDA receptors is an essential factor for increasing DBI expression in the
      neurons.

PMID- 11295243
TI  - Differences in NOS protein expression and activity in the rat vestibular nucleus
      following unilateral labyrinthectomy.
AB  - We used Western blotting to analyse the expression of different isoforms of
      nitric oxide synthase (NOS) in the rat vestibular nucleus complex (VNC) at
      various times following unilateral vestibular deafferentation (UVD), together
      with a radioenzymatic assay to compare NOS activity at the same time points. nNOS
      expression did not change significantly in the ipsilateral or contralateral VNC
      at any time following UVD. However, eNOS expression decreased significantly
      (P<0.05) in the contralateral VNC at 6 h post-UVD, recovering to normal levels by
      50 h. iNOS was not expressed at any time following UVD. NOS activity demonstrated
      a significant increase in the contralateral VNC at 6 h post-UVD (P<0.05),
      recovering toward normal levels by 50 h.

PMID- 11295244
TI  - Developmental dependency of Merkel endings on trks in the palate.
AB  - Immunohistochemistry for protein gene product 9.5 was performed on Merkel cells
      in the palate of wildtype and knockout mice for trkA, trkB or trkC. In wildtype
      mice, numerous Merkel cells were observed at the top of anterior four rugae. In
      the posterior four rugae, Merkel cells were fewer and mostly located at the base
      of rugae. In knockout mice for trkA, trkB and trkC, Merkel cells at the top of
      rugae mostly disappeared although those at the base of rugae remained unchanged.
      Therefore, the number of Merkel cells in anterior four rugae decreased. In
      posterior four rugae, however, the number of Merkel cells in the mutant mice was
      similar to that for wildtype mice. Immunohistochemistry for S100 also
      demonstrated that the loss of genes for trkA, trkB and trkC caused the absence of
      the immunoreactive innervation of Merkel cells. The normal development of Merkel
      endings at the top of palatal rugae is probably dependent on trkA, trkB and trkC.

PMID- 11295245
TI  - Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats.
AB  - The hypocretins (also known as orexins) are hypothalamic peptides that have been
      implicated in feeding and sleep regulation. Previous reports have described the
      distribution of the mRNAs encoding two hypocretin receptors (HCRT-R), but the
      pattern of protein expression has not been investigated. Here we examine the
      distribution of the mRNA and protein for the HCRT receptor 1 (HCRT-R1) and HCRT
      receptor 2 (HCRT-R2) in the pontine brainstem and demonstrate that they are
      present in many pontine nuclei including those associated with REM sleep.
      Immunohistochemistry indicates that one or both of the receptor subtypes are
      expressed in the dorsal raphe, the lateral dorsal tegmental (LDT), the pedunculo
      pontine (PPT), the locus coeruleus (LC), the locus subcoeruleus, pontis oralis,
      Barrington's, the trigeminal complex (mesencephalic trigeminal and motor nucleus
      of the trigeminal nerve), the dorsal tegmental nucleus of Gudden (DTG), the
      ventral cochlear nucleus (VCA), trapezoid nucleus (TZ), pontine raphe nucleus and
      the pontine reticular formation. These regions have been shown to be involved in
      mastication, bladder control, gastrointestinal function and in arousal. Given
      these projection sites and the functions associated with these sites, we suggest
      that HCRT may play a role in maintaining alertness and vigilance while the animal
      is engaged in consummatory behavior.

PMID- 11295246
TI  - A point mutation in the human connexin32 promoter P2 does not correlate with X
      linked dominant Charcot-Marie-Tooth neuropathy in Germany.
AB  - The sensorimotor neuropathy Charcot-Marie-Tooth disease (CMT) is the most common
      hereditary disorder of the peripheral nervous system. The X-linked dominant form
      of CMT (CMTX) is associated with mutations in the connexin32 gene (Cx32). The
      majority of CMTX cases harbour mutations in the coding region while a few cases
      have been reported to result from mutations in the promoter region. We found a G
      713A transition of the nerve specific Cx32 promoter P2 in the Caucasian German
      population. The allele frequency reached 50%, both in CMT patients and in healthy
      control individuals. In contrast, in an earlier contribution to this journal
      [Brain Res. Mol. Brain Res.78 (2000) 146], the same base transition was reported
      to cause CMTX in a Taiwanese family. These divergent results are important for
      genetic counselling and require careful consideration of ethnic backgrounds and
      of diagnostic and experimental pitfalls.

PMID- 11295247
TI  - Selective upregulation of the flip-flop splice variants of AMPA receptor subunits
      in the rat spinal cord after hindpaw inflammation.
AB  - Glutamate receptors are involved in spinal nociceptive transmission and the
      development of persistent inflammatory hyperalgesia. It is unclear, however,
      whether there are changes in glutamate receptor gene expression associated with
      tissue injury. In the present study, we used reverse transcription-polymerase
      chain reaction (RT-PCR) to examine the modulation of alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptor gene expression in the rat
      spinal cord by inflammation. Inflammation was introduced into the hindpaw by
      intraplantar injection of 0.2 ml of complete Freund's adjuvant (CFA). At 2 h-14 d
      after inflammation, total RNAs from L4,5 spinal cord were used for RT-PCR with
      primers targeted at eight flip-flop splice variants of the AMPA receptor
      subunits. It was found that the GluR1-flop mRNA was up-regulated at 2 h-5 h
      (P<0.05), down-regulated at 3 d (P=0.05), and returned to control levels at 7 d
      following inflammation. The GluR2-flip and GluR3-flop mRNAs were up-regulated at
      5 h-1 d (P<0.05) and returned to control levels at 3 d after inflammation. The
      GluR1-flip mRNA was not detected in the samples and the mRNAs for other splice
      variants did not exhibit significant changes. Immunocytochemical analysis of
      GluR1 and GluR2 subunits indicate that the protein translation products of these
      subunits were also increased in the spinal cord. These results demonstrate an
      increased expression of AMPA receptor subunits that correlates with the acute
      phase of CFA-induced inflammation and hyperalgesia. Selective changes in the
      expression of the flip-flop splice variants of the AMPA receptor suggest a
      reorganization of the composition of the AMPA receptor complex and its
      involvement in the development of inflammatory hyperalgesia.

PMID- 11295248
TI  - Distribution of 5-ht(5A), 5-ht(5B), 5-ht(6) and 5-HT(7) receptor mRNAs in the rat
      brain.
AB  - The precise involvement of 5-ht(5A), 5-ht(5B), 5-ht(6) and 5-HT(7) receptors in
      the pleiotropic actions of 5-HT remain incompletely known. To gain insights into
      their physiological function(s), localization of mRNAs encoding these subtypes
      was carried out using in situ hybridization on rat brain sections. Localization
      was heterogeneous. For example, 5-ht(5A) mRNA was widely expressed while 5-ht(5B)
      mRNA was predominantly expressed in habenula, hippocampus and inferior olive. 5
      ht(6) mRNA was abundant in olfactory tubercles and caudate putamen, and highest
      levels of 5-HT(7) mRNA were observed in multiple thalamic nuclei. These data
      suggest that these receptors may have distinct functional roles within the
      serotonergic system.

PMID- 11295249
TI  - Indexing-based differential display--studies on post-mortem Alzheimer's brains.
AB  - In this study we demonstrate for the first time that a novel indexing-based
      differential display technique generates valid and reproducible results when
      applied to human post-mortem tissue. We studied expression profiles in prefrontal
      cortex tissue derived from Alzheimer's disease (AD) and control brains,
      respectively, and found robust changes in several expressed genes, some of which
      have a known association with the disease process in AD. These included the
      dramatic reduction of calcineurin (known to be involved in tau phosphorylation)
      and GAP-43 (associated with synapse remodelling). Differential display results
      were confirmed by semi-quantitative RT-PCR on a larger number of brains.

PMID- 11295250
TI  - Cultured olfactory ensheathing cells express nerve growth factor, brain-derived
      neurotrophic factor, glia cell line-derived neurotrophic factor and their
      receptors.
AB  - In the primary olfactory pathway axons of olfactory neurons (ONs) are accompanied
      by ensheathing cells (ECs) as the fibres course towards the olfactory bulb.
      Ensheathing cells are thought to play an important role in promoting and guiding
      olfactory axons to their appropriate target. In recent years, studies have shown
      that transplants of ECs into lesions in the central nervous system (CNS) are able
      to stimulate the growth of axons and in some cases restore functional
      connections. In an attempt to identify a possible mechanism underlying EC support
      for olfactory nerve growth and CNS axonal regeneration, this study investigated
      the production of growth factors and expression of corresponding receptors by
      these cells. Three techniques immunohistochemistry, enzyme linked immunosorbent
      assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) were
      used to assess growth factor expression in cultured ECs. Immunohistochemistry
      showed that ECs expressed nerve growth factor (NGF), brain derived neurotrophic
      factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF). ELISA
      confirmed the intracellular presence of NGF and BDNF and showed that, compared to
      BDNF, about seven times as much NGF was secreted by ECs. RT-PCR analysis
      demonstrated expression of mRNA for NGF, BDNF, GDNF and neurturin (NTN). In
      addition, ECs also expressed the receptors trkB, GFRalpha-1 and GFRalpha-2. The
      results of the experiments show that ECs express a number of growth factors and
      that BDNF in particular could act both in a paracrine and autocrine manner.

PMID- 11295251
TI  - Percutaneous absorption and skin irritation of JP-8 (jet fuel).
AB  - JP-8 is the major jet fuel used by US Army and Air Force. The purpose of the
      present study was to investigate the percutaneous absorption of JP-8 across pig
      ear skin and human skin in vitro and to study the effect of JP-8 exposure on the
      skin barrier function and irritation in Yucatan minipigs. JP-8 spiked with 5.0
      microCi of radiolabeled (14C) tridecane, nonane, naphthalene or toluene (selected
      components of JP-8) was used for the in vitro percutaneous absorption studies
      with excised pig ear skin and human skin. For in vivo studies, 250 microl of JP-8
      or two of its components (toluene or nonane) was placed in a Hill top chamber(R)
      and affixed over the marked treatment area for 24 h. Transepidermal water loss
      (TEWL), skin capacitance (moisture content) and skin irritation (erythema and
      edema) were evaluated before treatment and at 1,2 and 24 h after removal of the
      patches. The components of JP-8 such as tridecane, nonane, naphthalene and
      toluene permeated significantly through pig ear skin and human skin and the
      permeation rates were found to be proportional to their composition in JP-8. The
      steady state flux values of tridecane across pig ear skin and human skin did not
      differ significantly (P>0.05). Though the steady state flux values of nonane,
      naphthalene and toluene were statistically different between porcine and human
      skin (P<0.01), the values were close considering the large variations usually
      observed in the percutaneous absorption studies. Application of toluene, nonane
      or JP-8 increased the TEWL, JP-8 being the highest (3.5 times at 24 h compared to
      baseline level). The skin moisture content decreased after the application of JP
      8, though it was not significantly different (P>0.05) from the baseline level. JP
      8 caused a moderate erythema and a moderate to severe edema. Though the edema
      decreased after 24 h, the degree of erythema remained about the same until 24 h.
      The skin irritation caused by JP-8 was greater than neat toluene or nonane. The
      TEWL data of toluene, nonane and JP-8 correlated well with the skin irritation
      data (erythema and edema). Exposure of JP-8, which contains hundreds of aliphatic
      and aromatic hydrocarbons, caused significant changes in the barrier function of
      the skin as indicated by an increase in TEWL and produced a significant erythema
      and edema in minipigs. Furthermore, the disruption of barrier function of skin,
      as indicated by increased TEWL after exposure to JP-8 might result in increased
      permeation of its own components and/or other chemicals exposed to skin. The
      present study provides further evidence that pig ear skin may be used as a model
      for predicting the rates of permeation of chemicals through human skin.

PMID- 11295252
TI  - Expression of urokinase-type plasminogen activator in an experimental model of
      hepatocarcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the
      liver. Molecular genetic analyses have clarified that accumulation of genome
      changes provides important steps in carcinogenesis. Urokinase type plasminogen
      activator (uPA) forms part of an important enzymatic system that degraded the
      extracellular matrix in process of invasion and metastasis. In order to study the
      kinetics of uPA cellular expression during this process, we used specific
      polyclonal antibodies against uPA in an immunohistochemistry assay in liver
      sections from a HCC in rats. The neoplastic transformation induced with this
      model was preceded by the appearance of numerous hyperplastic nodules during
      early stages, after time lesions progressed to well-differentiated HCC. The
      morphological changes of premalignant and malignant lesions were associated with
      a progressive increment of uPA expression, which reached its peak at 5 and 6
      months after the administration of the carcinogenic drugs. Of the enzymatic
      markers analyzed, the gamma glutamyl transpeptidase showed correlationship with
      the histological findings. Our results suggest that the increase in the uPA
      expression should not only be considered as the hallmark of metastasis, but may
      also be related to early events in the neoplastic transformation and with the
      proliferation of vessels and biliary ducts.

PMID- 11295253
TI  - Inhibition of oxidative DNA repair in cadmium-adapted alveolar epithelial cells
      and the potential involvement of metallothionein.
AB  - This study evaluated the effects of cadmium (Cd) adaptation in cultured alveolar
      epithelial cells on oxidant-induced DNA damage and its subsequent repair. Using
      the comet assay, we determined that lower levels of DNA damage occurred in Cd
      adapted cells compared with non-adapted cells following treatment of cells with
      hydrogen peroxide (H(2)O(2)). This may be a consequence of increased thiol
      containing antioxidants that were observed in adapted cells, including
      metallothionein and glutathione. Cd-adapted cells were, however, less efficient
      at repairing total oxidative DNA damage compared with non-adapted cells.
      Subsequently, we investigated the effect of Cd adaptation on the repair of
      particular oxidized DNA lesions by employing lesion-specific enzymes in the comet
      assay, namely formamidopyrimidine DNA glycosylase (Fpg), an enzyme that
      predominantly repairs 8-oxoguanine (8-oxoG), and endonuclease III, that is
      capable of repairing oxidized pyrimidines. The data demonstrated that adaptation
      to Cd results in significantly impaired repair of both Fpg- and endonuclease III
      sensitive lesions. In addition, in situ detection of 8-oxoG using a recombinant
      monoclonal antibody showed that Cd-adaptation reduces the repair of this
      oxidative lesion after exposure of cells to H(2)O(2). Activities of 8-oxoG-DNA
      glycosylase and endonuclease III were determined in whole cell extracts using 32P
      labeled synthetic oligonucleotides containing 8-oxoG and dihydrouracil sites,
      respectively. Cd adaptation was associated with an inhibition of 8-oxoG-DNA
      glycosylase and endonuclease III enzyme activity compared with non-adapted cells.
      In summary, this study has shown that Cd adaptation: (1) reduces oxidant-induced
      DNA damage; (2) increases the levels of key intracellular antioxidants; (3)
      inhibits the repair of oxidative DNA damage.

PMID- 11295254
TI  - Toxicological effects in rats chronically fed low dietary levels of fumonisin
      B(1).
AB  - The toxicity of low dietary levels of fumonisin B(1) (FB(1)), i.e. 1, 10 and 25
      mg FB(1)/kg diet, were monitored in rats over a period of 24 months. No effects
      on the body weight gain and feed intake profiles were noticed, while the relative
      liver weight was significantly (P<0.05) reduced in the FB(1)-treated rats. Mild
      toxic effects, including single cell necrosis (apoptosis), proliferation of bile
      duct epithelial cells (DEC), and early signs of fibrosis, bile duct hyperplasia
      and in one case, adenofibrosis, were noticed in the liver of the rats fed the
      highest (25 mg/FB(1)/kg diet) dietary level. A significant (P<0.05) increase in
      the level of oxidative damage was also noticed in the liver of the rats of high
      dosage dietary group. The toxic effects were less severe in the 10 mg FB(1)/kg
      dietary group, whilst only a few ground glass foci were observed in the 1 mg
      FB(1)/kg dietary group. Hepatocyte nodules, staining positively for glutathione-S
      transferase (placental form, PGST), were observed macroscopically in the 25 mg
      FB(1)/kg treated group and to a lesser extent in the 10 mg FB(1)/kg treated rats.
      The most prominent toxic lesions by FB(1) (10 and 25 mg FB(1)/kg dietary groups)
      in the kidneys were restricted to the tubular epithelium manifesting as granular
      cast, necrosis, apoptosis, calcification and the presence of regenerative foci in
      the proximal convoluted tubules. The existence of a cytotoxic/proliferative
      threshold with respect to cancer induction by FB(1) in rat liver became apparent,
      with a dietary level of <10-mg FB(1)/kg diet as a no effect threshold for the
      induction of hepatocyte nodules.

PMID- 11295256
TI  - The effects of inhalation exposure to bromo-dichloromethane on specific rat CYP
      isoenzymes.
AB  - Several cytochrome P450 (CYP) isoenzymes may be involved in the metabolism of
      bromo-dichloromethane (BDCM), a drinking water disinfection byproduct. After 4-h
      inhalation exposures of male F344 rats to BDCM between 100 and 3200 p.p.m.,
      hepatic microsomal methoxyresorufin demethylase (MROD), ethoxyresorufin de
      ethylease (EROD) and pentoxyresorufin dealkylase (PROD) activities showed modest
      increases at low exposure levels and larger decreases at high exposure levels,
      compared with controls. Western blots for CYP1A2 and CYP2B1 showed similar
      trends. In addition, p-nitrophenol hydroxylase (PNP) activity was measured and
      Western blots for CYP2E1 were performed. CYP2E1 and CYP2B1 isoenzymes are known
      to metabolize BDCM (Thornton-Manning, J.R., Gao, P., Lilly, P.D., Pegram, R.A.,
      1993. Acute bromodichloromethane toxicity in rats pretreated with cytochrome P450
      inducers and inhibitors. The Toxicologist 13: 361). When compared with a multiple
      gavage study of BDCM in female F344 rats (Thornton-Manning, J.R., et al., 1994.
      Toxicology 94, 3-18), the results of the two studies for EROD, PROD, and PNP
      activities were qualitatively the same; PNP activity did not change, while both
      PROD and EROD activities decreased at high exposures. In the current work,
      Western blots for CYP2E1, CYP2B1 and CYP1A2 supported the results from the PNP,
      PROD and MROD activities, respectively. The decreases in MROD and PROD activities
      and in Western blots for CYP1A2 and CYP2B1 at high exposures suggest that BDCM
      may be a suicide substrate for these CYP isoenzymes. Other important conclusions
      that can be drawn from the comparison between the current and prior work are that
      the liver response is similar for both sexes, and it is also similar for
      inhalation and gavage exposures under these conditions. Finally, the decrease in
      EROD activity at high doses, found in both studies, may be a further reflection
      of CYP1A2 activity, since little or no CYP1A1 activity is normally found in
      uninduced rat liver and CYP1A2 is known to metabolize ethoxyresorufin, although
      much more slowly than CYP1A1.

PMID- 11295255
TI  - Morphology and cytochrome P450 isoforms expression in precision-cut rat liver
      slices.
AB  - Precision-cut liver slices are a widely accepted in vitro system for the
      examination of drug metabolism, enzyme induction, or hepatotoxic effects of
      xenobiotics. The maintenance of the distinct lobular expression and induction
      pattern of phase I biotransformation enzymes, however, has not been examined
      systematically so far. Thus, in the present study, both longitudinal and
      transversal sections of male rat liver slices were investigated morphologically,
      as well as immunohistochemically for the expression of different cytochrome P450
      (CYP) isoforms after prolonged incubation or after exposure to typical inducers.
      Histopathological examinations revealed an increasing vacuolization of the
      periportal hepatocytes mainly in the middle of the slices from 6 h of incubation
      on, paralleled by a loss of glycogen in the respective cells. After 24 h, mainly
      in the center of the slices, necroses of cells occurred. After 48 h of
      incubation, typically a central band of coagulative necrosis flanked by
      superficial layers of viable cells was observed. Freshly prepared slices
      displayed a CYP subtypes expression as normal liver specimen, a very low
      centrilobular CYP 1A1 immunostaining, but a strong CYP 2B1 and 3A2 expression
      predominantly in the central and intermediate lobular zones. From 2 h on, the
      immunostaining for CYP 2B1 and 3A2 was to some extent reduced. After 24 h of
      incubation with beta-naphthoflavone, the CYP 1A1 and 2B1 expression was induced
      mainly in the viable cells around central veins, around some portal fields with
      bigger vessels and in the cell layers close to the slice surface. At the same
      sites, phenobarbital led to an increased CYP 2B1 and 3A2 expression and
      dexamethasone to an elevated CYP 3A2 immunostaining. These results show, that an
      in vitro induction of phase I enzymes in precision-cut liver slices can be
      demonstrated also immunohistochemically.

PMID- 11295258
TI  - Aluminum bioavailability from drinking water is very low and is not appreciably
      influenced by stomach contents or water hardness.
AB  - The objectives were to estimate aluminum (Al) oral bioavailability under
      conditions that model its consumption in drinking water, and to test the
      hypotheses that stomach contents and co-administration of the major components of
      hard water affect Al absorption. Rats received intragastric 26Al in the absence
      and presence of food in the stomach and with or without concomitant calcium (Ca)
      and magnesium (Mg) at concentrations found in hard drinking water. The use of
      26Al enables the study of Al pharmacokinetics at physiological Al concentrations
      without interference from 27Al in the environment or the subject. 27Al was
      intravenously administered throughout the study. Repeated blood withdrawal
      enabled determination of oral 26Al bioavailability from the area under its serum
      concentrationxtime curve compared to serum 27Al concentration in relation to its
      infusion rate. Oral Al bioavailability averaged 0.28%. The presence of food in
      the stomach and Ca and Mg in the water that contained the orally dosed 26Al
      appeared to delay but not significantly alter the extent of 26Al absorption. The
      present and published results suggest oral bioavailability of Al from drinking
      water is very low, about 0.3%. The present results suggest it is independent of
      stomach contents and water hardness.

PMID- 11295257
TI  - Mitochondrial dysfunction by gamma-irradiation accompanies the induction of
      cytochrome P450 2E1 (CYP2E1) in rat liver.
AB  - Multiple biological effects are induced by ionizing radiation through dysfunction
      of cellular organelles, direct interaction with nucleic acids and production of
      free radical species. The expression of cytochrome P450s was assessed in the
      livers of 60Co gamma-irradiated rats. Three gray (G) of gamma-irradiation caused
      CYP2E1 induction with a 3.6-fold increase in the mRNA at 24 h, whereas the
      expression of CYP1A2 and CYP3A was not changed. Pharmacokinetics of
      chlorzoxazone, a specific substrate of CYP2E1, was studied in 3 G-irradiated
      rats. The area under the plasma concentration-time curve from time zero to
      infinity of 6-hydroxychlorzoxazone and the amount of 6-hydroxychlorzoxazone
      excreted in 8 h urine were both significantly greater than those in control rats.
      Hepatic CYP2E1 was not induced in rats exposed to 0.5-1 G of gamma-rays. Rats
      irradiated at 6-9 G accumulated doses of gamma-rays exhibited smaller increases
      in the mRNA due to liver injury than those irradiated at a single dose of 3 G
      gamma-rays. The plasma glucose and insulin levels were not altered in rats with 3
      G of gamma-irradiation. As the exposure level of gamma-irradiation increased, the
      activity of hepatic aconitase, a key enzyme in energy metabolism in mitochondria,
      was 30-90% decreased. The amount of mitochondrial DNA per gram of wet liver was
      50% decreased in rats exposed to 3 G of gamma-rays. These results demonstrated
      that gamma-ray irradiation at the exposure level inducing organelle dysfunction
      induced CYP2E1 in the liver, which might be associated with mitochondrial damage,
      but not with alterations in glucose or insulin levels.

PMID- 11295259
TI  - Monooxygenation, conjugation and other functions in cryopreserved rat liver
      slices until 24 h after thawing.
AB  - For the extensive use of precision-cut liver slices (particularly of human
      origin) for toxicological investigations successful cryopreservation is
      necessary. But so far, survival of thawed slices was limited to few hours. This
      was now overcome by modification of previous procedures. The concentration of
      DMSO as a cryoprotectant was enhanced to 30%, and washing steps after rapid
      thawing were omitted. The slices were frozen in liquid nitrogen, thawed at 38
      degrees C and incubated immediately in Williams medium E. Protein and potassium
      contents were stable until 24 h. Glutathione content, amounting to nearly 50% of
      fresh slices, increased during incubation. High initial lactate dehydrogenase
      leakage dropped after medium change to less than half during 2-24 h. Testosterone
      hydroxylation and 7-ethoxycoumarin O-deethylation rates were similar to fresh
      slices, the latter reaction was inducible by beta-naphthoflavone within 24 h.
      Methylumbelliferone glucuronidation and p-nitrophenol glucuronidation and
      sulfation were well measurable and either maintained or decreased by about 50%
      until 24 h.Altogether, the results are encouraging for further experiments to
      standardise cryopreservation conditions and to investigate the suitability of
      this cryopreservation protocol with human liver slices.

PMID- 11295260
TI  - Repetitive nerve stimulation and stimulation single fiber electromyography
      studies in rats intoxicated with single or mixed insecticides.
AB  - The function of the neuromuscular transmission in rats dosed with phoxim (P),
      methomyl (M), fenvalerate (F), and mixtures of P+M and P+F was studied by using
      both the stimulation single fiber electromyography (SSFEMG) and repetitive nerve
      stimulations (RNS) to determine the single muscle fiber action potential and
      compound muscle action potential (CMAP) respectively. The results showed that the
      mean consecutive difference (MCD) in SSFEMG was significantly prolonged in P, P+M
      and P+F intoxicated rats during the presence of myasthenia, but not in rats dosed
      with F and M when stimuli were given at 10 Hz or 20 Hz, thus indicating a
      transmission blocking at the neuromuscular junction (NMJ) induced by P. The
      frequency of neuromuscular transmission abnormalities detected by SSFEMG was
      significantly higher than those detected by RNS. This study demonstrated that the
      neuromuscular junction (NMJ) blocking is more frequently seen in P, P+M and P+F
      poisoning than in M and F poisoning, and that SSFEMG is a more sensitive
      electrophysiological method than RNS for detecting neuromuscular transmission
      blockage in myasthenia rats with acute insecticides poisoning.

PMID- 11295261
TI  - Cadmium-induced alterations of connexin expression in the promotion stage of in
      vitro two-stage transformation.
AB  - During the multistage carcinogenesis, functions of several key genes involved in
      the cell cycle control and cell-cell communication can be damaged. Gap junction
      intercellular communication (GJIC) is known to transfer small, water-soluble
      molecules through intercellular channels composed of proteins called connexins
      (Cxs). Therefore, aberrant expression of Cx may be one of the critical factors
      for the clonal expansion of initiated cells during the two-stage transformation.
      We already improved the classical in vitro two-stage transformation method using
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as an initiator and cadmium as a
      promoter on Balb/3T3 A31 cells, and reconfirmed the promotional effect of cadmium
      with this method (Fang, M.Z., Cho, M.H., Lee, H.W., 2001. Improvement of in vitro
      two-stage transformation assay and detection of the promotional effect of
      cadmium, Toxicol. In Vitro (in press). In this study, precise roles of Cd on Cx
      expression in normal Balb/3T3 A31 and during the promotion stage of the in vitro
      two-stage transformation were elucidated. For this purpose, the Cx43, Cx32 and
      Cx26 protein levels, Cx43 and Cx26 mRNA levels and the cellular distribution
      location of Cx43 protein were determined. Normal Balb/3T3 cells expressed Cx43
      and Cx32, but not Cx26. After a short-term treatment of cadmium on normal cells,
      phosphorylation of Cx43 protein increased and Cx32 protein level decreased.
      However, during the promotion stage of the in vitro two-stage transformation,
      transformed cells treated with cadmium for long periods expressed Cx43 and Cx32
      highly, similar to the level of normal Balb/3T3 cells, compared to the
      nontransformed cells. Moreover, Cx43 of the transformed cells was distributed
      mostly in the perinuclear region rather than the intercellular membrane. These
      data suggest that cadmium may inhibit the GJIC by increasing the phosphorylation
      of Cx43 and decreasing the expression of Cx32 in the normal Balb/3T3 A31 cells.
      Our results also suggest that these changes are not associated with the cell
      transformation; transformed cells may reexpress Cx43 and Cx32 similar to the
      normal cells, though Cx43 protein is distributed aberrantly during the
      transformation process. Further studies are needed to clarify the relationship
      between transformation and posttranslational modification of the Cx proteins.

PMID- 11295262
TI  - Induction of metallothionein in the liver of carbon tetrachloride intoxicated
      rats: an immunohistochemical study.
AB  - Metallothioneins (MTs), are low molecular weight proteins, mainly implicated in
      metal ion detoxification. In the present study, we investigated the expression of
      hepatic MT in a rat model of injury and regeneration, induced by carbon
      tetrachloride (CCl(4)) administration. A single intraperitoneal injection of 1 ml
      CCl(4)/kg body weight was performed in male Wistar rats, killed at different time
      points post-administration. The enzymatic activities of aspartate and alanine
      aminotransferases in serum were determined, in addition to the liver histological
      findings, to estimate hepatotoxicity. The rate of tritiated thymidine
      incorporation into hepatic DNA, the enzymatic activity of thymidine kinase in
      liver tissue and the assessment of the mitotic index in hepatocytes, were used as
      indices of regeneration. MT was detected immunohistochemically in liver tissue
      sections. CCl(4) administration caused severe hepatic injury, followed by
      regeneration. MT expression became prominent as early as 12 h after the
      administration of CCl(4), in the nuclei of hepatocytes, while at 24 and 36 h
      intense cytoplasmic staining for MT appeared in the hepatocytes in the vicinity
      of necrotic areas. The peak of hepatocyte proliferative capacity, occurring at 48
      h post-CCl(4) administration coincides with the maximum nuclear and cytoplasmic
      MT expression. At further time points MT expression presented a decreasing trend.
      Induction of MT expression was observed in the liver after a single
      administration of CCl(4), being more prominent at the time of maximum
      hepatocellular proliferation, participating actively in the replication of
      hepatocytes.

PMID- 11295263
TI  - Superinduction of TNF-alpha and IL-6 in macrophages by vomitoxin (deoxynivalenol)
      modulated by mRNA stabilization.
AB  - Vomitoxin (VT or deoxynivalenol), a trichothecene, superinduces proinflammatory
      cytokine gene expression in vitro and in vivo. To better understand the
      underlying molecular mechanisms for this observation, post-transcriptional
      effects of VT on TNF-alpha and IL-6 gene expression were studied in
      lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. VT was found to
      enhance both TNF-alpha and IL-6 protein secretion in the presence of LPS. Upon
      addition of the transcriptional inhibitor, 5,6-dichloro-1-beta-D-ribofuranosyl
      benzimidazole (DRB), secretion of both cytokines was inhibited. Using Northern
      analysis, the mRNA stabilities of TNF-alpha and IL-6 were studied in DRB-treated
      cells exposed to VT and LPS in both asynchronous and delayed synchronous modes.
      In the asynchronous model, cells were first incubated with LPS for 2 h, and then
      the medium was removed and replaced with medium containing DRB and VT. In the
      delayed synchronous model, cells were pretreated with LPS for 2 h and then DRB
      and VT were added to the culture. TNF-alpha and IL-6 mRNA were rapidly stabilized
      by VT (100 and 250 ng/ml) in both asynchronous and delayed synchronous models. In
      the asynchronous model, TNF-alpha mRNA half-life was 25 min but this was extended
      in the presence of 100 and 250 ng/ml of VT to >3 h. VT also extended half-lives
      of IL-6 mRNA from 60 min to >3 h. In the delayed synchronous model, the half
      lives for TNF-alpha and IL-6 mRNA of 1.3 and 1.5 h, respectively, were extended
      to >3 h upon incubation with 100 and 250 ng/ml VT. These results suggest that
      post-transcriptional control via enhancement of mRNA stability is likely to
      contribute to proinflammatory cytokine superinduction in macrophages by VT and
      other trichothecenes.

PMID- 11295265
TI  - Fibroadenomas: computer-assisted quantitative evaluation of contrast-enhanced
      power Doppler features and correlation with histopathology.
AB  - We aimed to evaluate whether the histopathologic variability of fibroadenomas
      accounts for their varied appearance in contrast enhanced power Doppler (PD).
      Forty patients with fibroadenomas (aged 19 to 61 years) underwent power Doppler
      ultrasound (US) prior to and following IV bolus injection of a microbubble
      contrast agent. A 3-min computer-assisted assessment of the color pixel density
      (CPD) was used for objective evaluation of the increase in color Doppler signals.
      Enhancement characteristics were correlated to histopathologic features of
      microvessel density and epithelial hyperplasia, patient's age, tumor size, use of
      exogenous hormones and menopausal status. Epithelial hyperplasia was diagnosed in
      19 patients. Compared to baseline values, patients with epithelial hyperplasia
      showed a significant increase in mean CPD following contrast media administration
      (p < 0.01). There was a significant correlation to patient's age (p < 0.0001) and
      tumor size (p < 0.0001), but not to the use of exogenous hormones and menopausal
      status. Microvessel counts did not show a significant correlation to CPD at
      baseline (p = 0.07) or with CPD on contrast enhanced PD (p = 0.13), or with
      patient age (p = 0.43) or tumor size (p = 0.34). Intratumoral epithelial
      hyperplasia, primarily occurring in young patients, may contribute to the
      differential diagnostic overlap in some fibroadenomas and thus limit the ability
      of PD to distinguish between benign and malignant masses on the basis of
      enhancement characteristics.

PMID- 11295266
TI  - Short-time ultrasound of head and neck squamous cell carcinoma under
      radiotherapy.
AB  - To evaluate the efficacy of ultrasonography for patients with head and neck
      squamous cell carcinoma before and during radiotherapy (RT), consecutive patients
      with macroscopic lesions were examined before and during RT. Each scan was
      performed percutaneously in a short time (less than 5 min). The demonstration
      rate of primary tumors and the largest node of previously known metastatic
      cervical nodes were measured. Of all 190 patients, 91 primary tumors were
      detected (47.9%). Primary tumors in oral cavity, oropharynx, hypopharynx and
      cervical esophagus were determined in over 70% and, for those of nasopharynx and
      larynx, the demonstration rates were 30% or less. Nodal metastases were
      visualized in 78 of 80 patients with regional metastases (97.5%). Using the above
      information, 73 patients (38.4%) received the benefit of radiation therapy. Short
      time sonography is a valuable modality for patients with selected sites of head
      and neck cancers.

PMID- 11295267
TI  - Sonographic parenchymal and brain perfusion imaging: preliminary results in four
      patients following decompressive surgery for malignant middle cerebral artery
      infarct.
AB  - To investigate new methods of diagnostic transcranial sonography for brain
      parenchymal, vascular and perfusion imaging, we performed 3-D native tissue
      harmonic transcranial sonography (3D-nthTCS), 3-D transcranial color-coded duplex
      sonography (3D-TCCS), and "loss-of-correlation" imaging (LOC-TCCS) in four
      patients following early hemicraniectomy due to space-occupying "malignant"
      middle cerebral artery infarction (MMCAI). Three-dimensional datasets, utilizing
      3D-nthTCS and 3D-TCCS, were created and up to 10 axial 2-D B-mode image planes,
      similar to CCT, reconstructed in each patient. Three-dimensional reconstructions
      of the circle of Willis documented one persistent carotid-T occlusion and three
      recanalizations of the MCA. LOC-TCCS, based on stimulated acoustic emission from
      an ultrasound (US) contrast agent, demonstrated a perfusion deficit in 2 of 3
      patients, with regard to their infarcts. Concluding, 3D-nthTCS, 3D-TCCS and LOC
      TCCS are promising tools for bedside monitoring, early prognosis and treatment
      evaluation for MMCAI in the postoperative period. Further studies should be
      performed to standardize these new methods and evaluate their applications
      through the intact calvarina.

PMID- 11295268
TI  - Real-time visualization of high-intensity focused ultrasound treatment using
      ultrasound imaging.
AB  - High-intensity focused ultrasound (HIFU) and conventional B-mode ultrasound (US)
      imaging were synchronized to develop a system for real-time visualization of HIFU
      treatment. The system was tested in vivo in pig liver. The HIFU application
      resulted in the appearance of a hyperechoic spot at the focus that faded
      gradually after cessation of HIFU exposure. The duration of HIFU exposure needed
      for a hyperechoic spot to appear, was inversely related to the HIFU intensity.
      The threshold intensity required to produce a hyperechoic spot in liver in < 1 s
      was 970 W/cm(2), in situ. At this HIFU dose, no immediate cellular damage was
      observed, providing a potential for pretreatment targeting. The real-time
      visualization method was used in hemostasis of actively bleeding internal pelvic
      vessels, allowing targeting and monitoring of successful treatment. Real-time US
      imaging may provide a useful tool for image-guided HIFU therapy.

PMID- 11295269
TI  - Online motion-gated dynamic three-dimensional echocardiography in the fetus-
      preliminary results.
AB  - The aim of this study was to visualise the fetal heart in dynamic three
      dimensions (4-D) during an ultrasound (US) scan (online), rather than after
      (offline). With special pairing and sequential setting to minimise interference
      between two scanners, umbilical arterial Doppler waveforms (UADWs) from one
      scanner were used as an online motion gating source to trigger simultaneous 3-D
      cardiac structural data acquisition by another. Of 25 data sets from 10 fetuses,
      18 were acquired in 15 to 30 s per set with > or = 50% Doppler waveforms
      efficiently converted to triggering signals. Of 15 valid 4-D data sets, 10 were
      reconstructed in 2 to 20 min, compared to over 2 h previously reported (mainly
      for offline gating). Fine structures (including chordae tendinae and trabecular
      muscles) were depicted in six sets. The main problems in degrading 4-D images
      were extensive shadowing (6) from bony structures during rigid mechanical
      scanning, and random motion artefacts (6) from prolonged setting-up time with a
      complex combination of several systems. Integration of these systems is,
      therefore, recommended.

PMID- 11295270
TI  - Conversion of umbilical arterial Doppler waveforms to cardiac cycle triggering
      signals: a preparatory study for online motion-gated three-dimensional fetal
      echocardiography.
AB  - To remove motion artefacts, a device was built to convert "noisy" umbilical
      arterial Doppler waveforms (UADWs) from an ultrasound (US) system into sharp ECG
      R-wave-like cardiac cycle triggering signals (CCTSs). These CCTSs were then used
      to gate a simultaneous (online) 3-D acquisition of sectional fetal
      echocardiograms from another US system. To test the conversion performance, a
      study was carried out in sheep fetal twins. Pulmonary arterial flow waveforms
      (PAFWs) from implanted probes were traced, in the meantime, to determine the
      reference cardiac cycle. Interference caused by running the two nonsynchronised
      US systems was controlled to three degrees (not-noticeable, moderate, and
      severe), together with high (> or = 40 cm/s) and low (< 40) flow velocities on
      UADWs. The conversion efficiency, assessed by the percentage of UADWs converted
      into CCTSs, was in the range of 83% to 100% for not-noticeable and moderate
      interference, and 0% to 71% for severe interference. The triggering accuracy,
      assessed by [(time lag mean between the onsets of PAFWs and corresponding CCTSs) 
      - (its 99% confidence level)] / the mean, was 90% to 96% for the not-noticeable
      interference high- and low-flow groups and for the moderate interference high
      flow group; 19% to 93% for the moderate interference low-flow group; and from not
      obtainable up to 90% for the severe interference groups. The results show that
      UADWs can be used as a satisfactory online motion-gating source even in the
      presence of moderate interference. The major problems are from severe
      interference or moderate interference with low-flow velocity, which can be
      minimised/eliminated by the integration of the individual systems involved.

PMID- 11295271
TI  - Serial measurement of cross-sectional area in peripheral vein grafts using three
      dimensional ultrasound.
AB  - Frequent surveillance of bypass grafts placed in the lower limbs can provide
      early detection of stenoses. A three-dimensional (3-D) ultrasound (US) imaging
      system has been used to produce serial surface reconstructions of regions of
      interest in vein grafts in the lower extremities. Using anatomical reference
      points, data sets from serial studies are registered in a common 3-D coordinate
      system. Cross-sectional area measurements are extracted from the surface
      reconstructions in planes normal to the vessel center axis. These measurements
      are compared at matched sites over time to track changes in the vessel
      configuration. The quantitative measurements are paired with surface displays of
      the vessels for a complete depiction of the changing geometry. Example studies
      from three patients are shown, for time periods up to 38 weeks. The cross
      sectional area measurements highlight regions of remodeling and developing
      stenoses within the grafts.

PMID- 11295272
TI  - Real-time three-dimensional color Doppler echocardiography for characterizing the
      spatial velocity distribution and quantifying the peak flow rate in the left
      ventricular outflow tract.
AB  - Quantification of flow with pulsed-wave Doppler assumes a "flat" velocity profile
      in the left ventricular outflow tract (LVOT), which observation refutes. Recent
      development of real-time, three-dimensional (3-D) color Doppler allows one to
      obtain an entire cross-sectional velocity distribution of the LVOT, which is not
      possible using conventional 2-D echo. In an animal experiment, the cross
      sectional color Doppler images of the LVOT at peak systole were derived and
      digitally transferred to a computer to visualize and quantify spatial velocity
      distributions and peak flow rates. Markedly skewed profiles, with higher
      velocities toward the septum, were consistently observed. Reference peak flow
      rates by electromagnetic flow meter correlated well with 3-D peak flow rates (r =
      0.94), but with an anticipated underestimation. Real-time 3-D color Doppler
      echocardiography was capable of determining cross-sectional velocity
      distributions and peak flow rates, demonstrating the utility of this new method
      for better understanding and quantifying blood flow phenomena.

PMID- 11295273
TI  - In vivo breast tissue backscatter measurements with 7.5- and 10-MHz transducers.
AB  - Measurements of the ultrasound (US) backscatter coefficient (BSC) of
      fibroglandular and fatty breast tissues in vivo from 5.25 through 13 MHz, using
      the reference phantom method, are presented. Radiofrequency echo data were
      collected at a series of locations in the left breasts of 16 adults, age 46 to
      84, and in a custom-built phantom calibrated for backscatter and attenuation.
      Matched regions of interest (ROIs) were then selected in these images, from which
      the backscatter coefficient and the backscatter frequency dependence were
      ratiometrically estimated, after compensation for attenuation. The mean results
      in fibroglandular tissues were 78.9 x 10(-3)/cm, sr at 7.2 MHz (n(ROI) = 43, n =
      13) and 146 x 10(-3)/cm, sr at 10.3 MHz (n(ROI) = 19, n = 10) with frequency
      dependencies of f(2.28) and f(3.25). The corresponding results in subcutaneous
      fat were 2.59 x 10(-3)/cm, sr at 7.2 MHz (n(ROI) = 56, n = 16) and 7.08 x 10(
      3)/cm, sr at 10.3 MHz (n(ROI) = 57, n = 16) with frequency dependencies of
      f(3.49) and f(3.43). These findings are discussed and compared to similar
      measurements in the literature.

PMID- 11295274
TI  - Quantification of flow rates using harmonic grey-scale imaging and an ultrasound
      contrast agent: an in vitro and in vivo study.
AB  - It is unclear if the dye-dilution theory and its corresponding parameters are
      capable of measuring brain perfusion using harmonic grey-scale imaging. We
      performed a study on a flow phantom using a SONOS 5500 (1.8--3.6-MHz harmonic
      imaging) and Levovist as the ultrasound (US) contrast agent (UCA). We applied the
      UCA in six different doses (0.1 to 3.0 mL) and used eight different flow-rates
      (180 to 540 mL/min). Additionally, we performed a study on dog brain using
      Levovist boluses of 1.5 mL and 3 mL. We evaluated the influence of dose and flow
      rate on the parameters of the time-intensity curve: peak signal intensity (PSI),
      area under the curve (AUC) and mean transit time (MTT). Along with an increase of
      the Levovist dose, the AUC and the PSI increased only in the dose range between
      0.1 and 0.5 mL Levovist; further increase led to no change of parameters. Flow
      rate showed no influence on AUC, MTT or PSI. The dye-dilution theory is not a
      useful theoretical model for the analysis of perfusion using harmonic grey-scale
      imaging. A possible explanation for this effect is the bubble saturation.

PMID- 11295275
TI  - Wavelet-based edge detection in ultrasound images.
AB  - We introduce a new wavelet-based method for edge detection in ultrasound (US)
      images. Each beam that is analyzed is first transformed into the wavelet domain
      using the continuous wavelet transform (CWT). Because the CWT preserves both
      scale and time information, it is possible to separate the signal into a number
      of scales. The edge is localized by first determining the scale at which the
      power spectrum, based on the wavelet transform, has its maximum value. Next, at
      this scale we find the position of the peak for the squared CWT. This method does
      not depend on any threshold, after the range of scales have been determined. We
      suggest a range of scales for US images in general. Sample edge detections are
      demonstrated in US images of straight and jagged edges of simple structures
      submerged in water bath, and of an abdominal aorta aneurysm phantom.

PMID- 11295276
TI  - Volume flow measurement using Doppler and grey-scale decorrelation.
AB  - A technique for volumetric blood flow measurement was developed by combining
      standard Doppler measurements with grey-scale decorrelation. Steered Doppler is
      used to determine the in-plane velocities, which are then used to extract the out
      of-plane velocities from the temporal A-line decorrelation. As a result, a three
      dimensional (3-D) vector flow field can be computed over the imaging plane using
      a single clinical transducer without knowledge of the vessel orientation. Volume
      flow is computed by integrating the out-of-plane flow over the vessel cross
      section. The algorithm was tested using a scattering-enhanced fluid in a 6.4-mm
      diameter dialysis tubing. For a wide range of transducer angles, the volume flow
      was accurately measured to within 28% in these preliminary tests.

PMID- 11295277
TI  - Apoptosis in ultrasound-produced threshold lesions in the rabbit brain.
AB  - Focused ultrasound (US) surgery has been used to induce high temperature
      elevations in tissue to coagulate the proteins and kill the tissue. The
      introduction of noninvasive online temperature monitoring has made it possible to
      induce well-controlled thermal exposures. In this study, we used magnetic
      resonance imaging (MRI) thermometry to monitor thermal exposures near the
      threshold of tissue damage, and then investigated if apoptosis was induced.
      Rabbit brains were sonicated with an eight-sector phased array to create a large
      region of uniform temperature elevation at the end of a 30-s sonication.
      Histological examination demonstrated that apoptosis was induced in some cells.
      At 4 h after the sonications, the apoptotic cells constituted 9 +/- 7% of
      identifiable cells. By 48 h after the sonications, the number of apoptotic cells
      had increased up to 17 +/- 9%. The impact of this finding for therapy needs to be
      explored further.

PMID- 11295278
TI  - Dynamics of bubble oscillation in constrained media and mechanisms of vessel
      rupture in SWL.
AB  - Rupture of small blood vessels is a primary feature of the vascular injury
      associated with shock-wave lithotripsy (SWL) and cavitation has been implicated
      as a potential mechanism. To understand more precisely the underlying mechanical
      cause of the injury, the dynamics of SWL-induced bubble dynamics in constrained
      media were investigated. Silicone tubing and regenerated cellulose hollow fibers
      of various inner diameters (0.2 to 1.5 mm) were used to fabricate vessel
      phantoms, which were placed in a test chamber filled with castor oil so that
      cavitation outside the phantom could be suppressed. Degassed water seeded with
      0.2% Albunex contrast agent was circulated inside the vessel phantom, and
      intraluminal bubble dynamics during SWL were examined by high-speed shadowgraph
      imaging and passive cavitation detection via a 20-MHz focused transducer. It was
      observed that, in contrast to the typical large and prolonged expansion and
      violent inertial collapse of SWL-induced bubbles in a free field, the expansion
      of the bubbles inside the vessel phantom was significantly constrained, leading
      to asymmetric elongation of the bubbles along the vessel axis and, presumably,
      much weakened collapse. The severity of the constraint is vessel-size dependent,
      and increases dramatically when the inner diameter of the vessel becomes smaller
      than 300 microm. Conversely, the rapid, large intraluminal expansion of the
      bubbles causes a significant dilation of the vessel wall, leading to consistent
      rupture of the hollow fibers (i.d. = 200 microm) after less than 20 pulses of
      shock wave exposure in a XL-1 lithotripter. The rupture is dose-dependent, and
      varies with the spatial location of the vessel phantom in the lithotripter field.
      Further, when the large intraluminal bubble expansion was suppressed by inversion
      of the lithotripter pressure waveform, rupture of the hollow fiber could be
      avoided even after 100 shocks. Theoretical calculation of SWL-induced bubble
      dynamics in blood confirms that the propensity of vascular injury due to
      intraluminal bubble expansion increases with the tensile pressure of the
      lithotripter shock wave, and with the reduction of the inner diameter of the
      vessel. It is suggested that selective truncation of the tensile pressure of the
      shock wave may reduce tissue injury without compromising the fragmentation
      capability of the lithotripter pulse.

PMID- 11295279
TI  - A real vessel phantom for flow imaging: 3-D Doppler ultrasound of steady flow.
AB  - Vascular phantoms are used to assess the capabilities of various imaging
      techniques, such as x-ray CT and angiography, and B-mode, power Doppler, and
      colour Doppler ultrasound (US). They should, therefore, accurately mimic the
      vasculature, blood, and surrounding tissue, in regard to both imaging properties
      and vessel geometry. In the past, a variety of walled and wall-less vessel models
      have been used. However, these models only approximate the true vessel geometry,
      and generally lack pathologic features such as plaques or calcifications. To
      amend these deficiencies, we have developed a real vessel phantom for US and x
      ray studies, which comprises a fixed human vessel specimen, cannulated onto two
      acrylic tubes, and embedded in agar in an acrylic box. Earlier, we demonstrated a
      good overall correlation between x-ray angiography, CT, and 3-D B-mode US images
      of this phantom. Here, we extend its use to flow imaging with 3-D power and 3-D
      colour Doppler US.

PMID- 11295280
TI  - Chromosomal rearrangements in thyroid carcinomas: a recombination or death
      dilemma.
AB  - Well differentiated thyroid carcinomas provide a unique model of human,
      epithelial cell carcinogenesis. Their molecular characterization has allowed to
      associate specific genetic alterations to the two papillary and follicular
      histotypes which, despite their common origin, display different biological and
      clinical behaviors. A common mechanism of oncogenic activation has been observed
      in these tumors, based on the peculiar characteristic of thyroid epithelium to
      generate fusion transforming genes by chromosomal rearrangements. The reasons for
      this peculiar uniqueness of thyrocytes are not known, but a structural
      explanation, based on the spatial contiguity in the interphase nuclei of
      thyrocytes of the two fused genes and enzymatic features of these cells which
      render them apoptosis resistant to DNA damage, have been proposed to account for
      this behavior.

PMID- 11295281
TI  - Growth inhibitory effect of green tea extract in Ehrlich ascites tumor cells
      involves cytochrome c release and caspase activation.
AB  - We reported previously that the mechanism by which Green tea extract (GTE)
      elicited growth-inhibitory effects in Ehrlich ascites tumor cells involved a
      decrease in ornithine decarboxylase (ODC) activity and in cell viability.
      Decrease in ODC activity has been associated with apoptotic cell death and we
      therefore studied changes in cytochrome c release and caspase activation, which
      characterize apoptosis. GTE caused a dose- and time-dependent increase in caspase
      3-like protease activation, preceded by a release of cytochrome c from the
      mitochondria. Inhibiting the activation of caspase-3 with acetyl-Asp-Glu-Val-Asp
      alpha-aldehyde (caspase inhibitor) caused a reversal in the effect on cell
      viability.

PMID- 11295282
TI  - Augmentation of macrophage functions by an aqueous extract isolated from
      Platycodon grandiflorum.
AB  - Platycodon grandiflorum has been claimed to have a wide range of health benefits,
      which include immunostimulation and antitumor activity. The associated biological
      mechanisms are unclear; however, of the wide diversity of effects, it is believed
      that their activities may be exerted through several potent effector cells such
      as macrophages. Therefore, the effects of an aqueous extract from the root of P.
      grandiflorum (Changkil: CK) on mouse peritoneal macrophage function were
      investigated. It was found that CK stimulated macrophage proliferation, spreading
      ability, phagocytosis, cytostatic activity, and nitric oxide production in a dose
      dependent manner, and that the production of cytokines such as TNF-alpha, IL
      1beta and IL-6 were similarly increased. CK significantly affected secretion at
      concentrations greater than 10 microg/ml; its maximal effects were at the
      concentration of 100 microg/ml. Reverse transcription-polymerase chain reaction
      showed that CK increased the appropriate cytokine mRNAs. These results suggest
      that CK is a potent enhancer of macrophage function.

PMID- 11295283
TI  - Soy protein isolate consumption protects against azoxymethane-induced colon
      tumors in male rats.
AB  - Male Sprague-Dawley rats (F2 generation) that had been fed modified American
      Institute of Nutrition-93G diets formulated with a single protein source of
      either casein or soy protein isolate for their entire life received azoxymethane
      once a week for 2 weeks (s.c., 15 mg/kg) starting at age 90 days. Forty weeks
      later, all rats were euthanized, the colon was examined visually for masses and
      these were subsequently evaluated histologically. Rats fed the casein diet had a
      50% incidence of colon tumors compared with 12% on soy protein-based diets
      (P<0.05). These results suggest that consumption of soy protein-containing diets
      may reduce the risk of developing colon tumors.

PMID- 11295284
TI  - Enhancement of natural killer cell-mediated cytotoxicity by coexpression of GM
      CSF/B70 in hepatoma.
AB  - On investigating the role of granulocyte-macrophage colony-stimulating factor (GM
      CSF) and costimulatory molecule, B70, in antitumor immunity, we have found
      important effects of GM-CSF/B70 coexpression in the interaction with natural
      killer (NK) cells. We used the pLSN vector system to contain the neomycin
      resistant gene and LTR promoter. The pLSNGM-CSF, pLSNB70 and pLSNB70/GM-CSF, pLSN
      vectors each containing GM-CSF, B70, and B70/GM-CSF cDNA, respectively, were
      constructed. They were transfected into human hepatocellular carcinoma cell (SK
      HEP1), and stable cells (SK-pLSN, SK-GM, SK-B70 and SK-BG) were selected after
      neomycin treatment. According to enzyme-linked immunosorbent analysis and FACS,
      we showed that expression of GM-CSF was increased up to 23-fold in SK-GM and SK
      BG cells, and also expression of B70 was induced at least 76-97% in SK-B70 and SK
      BG cells. Expression of B70 was remarkably increased by autocrine effect of GM
      CSF in SK-BG cells. Primary cytolytic ability of GM-CSF and B70 significantly
      increased almost 4-fold (effector/target ratio, 100:1) in SK-BG cells. In in vivo
      studies, SK-BG cells showed much less subcutaneous tumor formation in nude mice
      accompanying increased NK cell proliferation and cytotoxicity. Therefore, these
      results suggest that combining expression of GM-CSF and B70 may enhance NK
      mediated cytotoxicity, and then induce the antitumor immunity in hepatoma
      transplanted into nude mice.

PMID- 11295285
TI  - The -238 tumor necrosis factor-alpha promoter polymorphism is associated with
      decreased susceptibility to cancers.
AB  - We investigated the potential association of tumor necrosis factor-alpha (TNF
      alpha) promoter polymorphisms with cancers. The study included 169 patients with
      gastric cancer, uterine cervical cancer, colorectal cancer, or renal cell
      carcinoma and 92 healthy controls. The -308 and -238 polymorphisms in the TNF
      alpha promoter were analyzed by PCR-restriction fragment length polymorphism
      (RFLP). The proportion of individuals carrying the TNF-238A allele was
      significantly lower in the cancer group than in the control group. The odds ratio
      for cancer in subjects with the TNF-238A allele was 0.25 (95% CI, 0.10-0.64). No
      association was found between the -308 polymorphism and cancers. These results
      suggest that the -238A allele has a protective function against cancers.

PMID- 11295286
TI  - Ras gene mutations in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat sarcomas.
AB  - Tumor induction in rats by 7,12-dimethylbenz[a]anthracene (DMBA) will generate
      malignancies that display reproducible chromosomal abnormalities involving rat
      chromosome (RNO) 2. Thus, it has been reported that rat DMBA erythroleukemias
      display RNO2 abnormalities, which in this case were closely correlated to
      mutations in the Nras oncogene located in RNO2q34. Our cytogenetic analysis in a
      series of 17 DMBA-induced rat sarcomas showed that 11 (65%) tumors had a
      significant increase in RNO2 copy number. Furthermore, the incidence of point
      mutations in codons 12, 13 and 61 of Hras, Kras, and Nras was examined in the
      same set of sarcomas, and mutations were detected in three (18%) tumors, in codon
      61 of Kras (CAA-->CAT) (1 of 17) and Nras (CAA-->CTA) (2 of 17). We conclude that
      the high frequency of RNO2 gain was in accordance with previous studies of DMBA
      induced rat neoplasms, supporting the idea of a significant role of RNO2 in DMBA
      carcinogenesis. However, there was no clear-cut relationship between activated
      Nras and gain of RNO2 material, implying that mutational activation of Nras is
      not the causative factor underlying the gain of RNO2 copy number in rat DMBA
      sarcomas, in contrast to what has been suggested for DMBA-induced
      erythroleukemias.

PMID- 11295287
TI  - Paradoxical effects of trichostatin A: inhibition of NF-Y-associated histone
      acetyltransferase activity, phosphorylation of hGCN5 and downregulation of cyclin
      A and B1 mRNA.
AB  - Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), is widely used
      to study the role of histone acetylation in gene expression, since genes that use
      histone acetylation as a means of regulating expression may be up regulated when
      TSA is added. In this study, however, we show that TSA has an unexpected
      paradoxical effect leading to inhibition of NF-Y-associated histone acetyl
      transferase (HAT) activity and phosphorylation of the HAT, hGCN5. TSA treatment
      of cells resulted in diminished levels of NF-Y-associated HAT activity without
      changes in NF-Y(A) amount. hGCN5 is one of the HATs known to associate with NF-Y.
      The association of hGCN5 with NF-Y was not altered by TSA treatment. The
      enzymatic activity of hGCN5 is known to be inhibited by phosphorylation. TSA
      treatment of Hela cells resulted in phosphorylation of hGCN5. Exposure of the NF
      Y immunoprecipitates from TSA-treated cells to a phosphatase resulted in enhanced
      HAT activity. We have also shown that the mRNA levels of several genes, cyclin B1
      and cyclin A, are downregulated by TSA; these effects do not require protein
      synthesis and the downregulation of cyclin B1 by TSA occurs through
      transcription. These results suggest that TSA can have contradictory effects, on
      one hand stimulating HAT activity in general by inhibition of HDACs, but also
      resulting in inhibition of NF-Y-associated HAT activity and phosphorylation of
      hGCN5.

PMID- 11295288
TI  - Somatic mutations and single nucleotide polymorphisms of base excision repair
      genes involved in the repair of 8-hydroxyguanine in damaged DNA.
AB  - To elucidate the involvement of 8-hydroxyguanine (oh(8)G) repair genes in human
      lung carcinogenesis, 47 lung cancer cell lines and 55 primary lung cancers were
      examined for somatic mutations and genetic polymorphisms in all coding exons of
      the MYH and APEX genes, and exon 8 of the OGG1 gene by polymerase chain reaction
      single strand conformation polymorphism analysis. In the MYH gene, one missense
      mutation was detected in a cell line, NCI-H157, whereas no mutations were
      detected in primary cancers. There were no mutations in the APEX and OGG1 genes
      in the cell lines or primary cancers. Ten single nucleotide polymorphisms (SNPs)
      were identified, and seven of them were accompanied by amino acid substitutions.
      Differences in the oh(8)G repair activities of MYH, APEX and OGG1 proteins due to
      somatic mutations and SNPs can be involved in human carcinogenesis.

PMID- 11295289
TI  - Decreased topoisomerase IIalpha expression confers increased resistance to ICRF
      193 as well as VP-16 in mouse embryonic stem cells.
AB  - To elucidate the relationship between topoisomerase (topo) II expression and
      sensitivity to anti-topo II drugs in mammalian cells, we generated mouse
      embryonic stem cell mutants heterozygous for the topo IIalpha gene by gene
      targeting. The level of topo IIalpha in the heterozygous cells reduced to one
      half of that found in wild-type cells, while topo IIbeta levels were similar in
      both cell types. Importantly, the heterozygous cells exhibited an increased
      resistance to ICRF-193 as well as VP-16, suggesting that ICRF-193, like VP-16,
      exerts its cytotoxicity through converting topo II to a poison.

PMID- 11295290
TI  - Competitive uptake of porphyrin and LDL via the LDL receptor in glioma cell
      lines: flow cytometric analysis.
AB  - We examined the simultaneous uptake of porphyrin and (LDL) by four established
      cell lines of glioma and normal fibroblasts using flow cytometry (FCM). The
      results indicated porphyrin and LDL showed competitive conjugation with the LDL
      receptor. These results support the theory of the porphyrin uptake via the LDL
      receptor.

PMID- 11295291
TI  - Quick quantitative analysis of gene dosages associated with prognosis in
      neuroblastoma.
AB  - The amplification of the N-myc gene and a gain of the chromosome 17q arm
      correlate with an unfavorable outcome in patients with neuroblastoma. In this
      study, we determined the gene dosage of the N-myc gene (located at 2p24) and
      Survivin gene (located at 17q25) using the p53 gene (located at 17p13) as the
      internal control gene by the TaqMan polymerase chain reaction (PCR)-based gene
      dosage analysis in 25 neuroblastoma samples. Based on the assumption that the
      gene dosages of each gene of a normal individual lymphocytes are 1.0, 11 of the
      25 cases with a corrected gene dosage of N-myc (N-myc/p53) of more than 2.0 had a
      more unfavorable prognosis than the 14 cases with a N-myc gene dosage of less
      than 2.0 (5-year survival rate: 18 vs. 71%, P<0.01). Ten of 25 cases with a
      corrected Survivin gene dosage (Survivin/p53) of more than 2.0 had a more
      unfavorable prognosis than the 15 cases with a Survivin gene dosage of less than
      2.0 (5-year survival rate: 10 vs. 67%, P<0.01). This quantitative PCR system is
      considered to be useful for quickly and accurately evaluating the degree of
      malignancy of neuroblastoma in order to select the optimal treatment.

PMID- 11295293
TI  - Clinicopathological and prognostic significance of thymidine phosphorylase and
      proliferating cell nuclear antigen in gastric carcinoma.
AB  - We have reported that thymidine phosphorylase (dThdPase) is identical to platelet
      derived-endothelial cell growth factor and that it has an angiogenic activity in
      vitro and in human carcinoma tissues as well as gastric carcinoma. Recently, we
      revealed that dThdPase may have an another function(s) besides angiogenesis in
      vitro and in human solid tumors. Using immunohistochemistry, we examined
      retrospectively whether the expression of dThdPase was correlated with tumor
      growth, comparing it with the proliferating cell nuclear antigen labeling index
      (PCNA LI) and examining their prognostic significance in 116 patients with
      gastric carcinoma. A direct correlation of these two factors was observed
      (R=0.659, P<0.001). A multivariate Cox regression analysis showed that both
      dThdPase positivity and PCNA LI were independent prognostic factors, as were
      depth of invasion and lymph node metastasis. Furthermore, the patients with
      dThdPase-positive/high PCNA LI tumors had the worst prognoses. The combination of
      dThdPase and PCNA expression is a better tool for predicting the prognosis of
      patients with gastric carcinoma than the expression of either of them alone.
      These results raise the possibility that dThdPase may have a function(s) involved
      in tumor growth besides angiogenesis.

PMID- 11295292
TI  - Evaluation of leukocyte arylsulfatase-A activity in patients with breast cancer
      and benign breast disease.
AB  - This study was planned to evaluate the feasibility of using the assay of
      leukocyte arylsulfatase-A (AS-A) activity as a non-invasive diagnostic tool in
      patients with benign and malignant breast disease. The leukocyte AS-A activity of
      a total of 81 women was analyzed, including 28 healthy women, 29 women with
      benign breast disease (BBD) and 24 patients with primary breast cancer (BC). The
      mean leukocyte AS-A activity in patients with BBD was slightly higher (14.3%)
      that observed in the healthy subjects, but the difference was not statistically
      significant. In patients with BC the enzyme activity was significantly higher
      than in the healthy subjects (60.3%, P<0.05) and in the benign group (40.2%,
      P<0.05). In addition, since no significant differences have been observed between
      premenopausal patients and their controls, it is suggested that the measurement
      of leukocyte AS-A activity may not be a reliable test for differential diagnosis
      of benign and malignant proliferation in mammary glands due to the possible
      interfering effect of gonadal hormones on AS-A activity. In contrast, since peri-
      and postmenopausal BC patients have negligible or no gonadal activity function,
      the elevation in the activity of leukocyte AS-A in these age groups of patients
      may only be expected to originate from malignant proliferation. Based on our
      results, it is concluded that in patients in whom high leukocyte AS-A activities
      were observed the possibility of the presence of malignancy might also be high.
      Therefore, this test might be valuable as a non-invasive biochemical technique in
      combination with other established markers for the identification of masses in
      the breast.

PMID- 11295294
TI  - 7-O-(6-O-benzoyl-beta-D-glucopyranosyl)-rutin from leaves of Canthium dicoccum.
AB  - A new flavonol glycoside, characterized as 7-O-(6-O-benzoyl-beta-D
      glucopyranosyl)-rutin (1), has been isolated from the leaves of Canthium
      dicoccum. Detailed 1H COSY, HSQC, HMBC and TOCSY NMR as well as positive and
      negative electrospray MS and MS/MS data have been provided for the new compound.

PMID- 11295295
TI  - Effect of methanolic extract of Cassia nigricans leaves on rat gastrointestinal
      tract.
AB  - The effects of the methanolic extract of Cassia nigricans leaves were
      investigated on experimentally-induced diarrhoea and ulceration in rat. The
      extract dose-dependently reduced both the small intestinal propulsive movement
      (P<0.01-0.001), and castor oil-induced fluid accumulation (P<0.05-0.001). Its
      inhibitory effects on intestinal propulsive movement and fluid accumulation were
      significantly (P<0.05) antagonised by yohimbine. However, castor oil-induced
      diarrhoea was increased. The extract also reduced significantly (P<0.05-0.001)
      the ulcers induced by both indomethacin and ethanol. The results indicate that
      the observed antidiarrhoeal effect might in part be due to alpha(2)-adrenoceptor
      stimulation.

PMID- 11295296
TI  - Ecdysteroids from two Brazilian Vitex species.
AB  - A new ecdysteroid, 26-hydroxypinnatasterone (1), together with 20
      hydroxyecdysone, was isolated from the stem barks of Vitex cymosa. 20
      Hydroxyecdysone, ajugasterone C, ajugasterone C monoacetonide and turkesterone
      were isolated from the branches of V. polygama. The structure of 1 was determined
      by spectroscopic methods.

PMID- 11295297
TI  - Topical anti-inflammatory activity of some Asian medicinal plants used in
      dermatological disorders.
AB  - The topical anti-inflammatory activity of extracts from Cassia angustifolia,
      Rheum palmatum, Coptis chinensis, Phellodendron amurense and Scutellaria
      baicalensis, plants used in traditional East Asian medicine against different
      skin disorders, was studied. Though in different degree, all the extracts
      significantly inhibited the edema induced by 12-O-tetradecanoylphorbol-13-acetate
      (TPA), in both single or multiple application, oxazolone, and arachidonic acid
      (AA). None of the extracts inhibited in vitro the activity of phospholipase A(2)
      (PLA(2)) from Naja naja.

PMID- 11295298
TI  - Effects of stem bark and leaf extracts of Bridelia ferruginea on rat bladder
      smooth muscle.
AB  - The effects of ethanol extracts of Bridelia ferruginea leaves and stem bark on
      purinergic neurotransmission in the rat bladder were investigated. The stem bark
      extract potentiated the contraction of the bladder evoked by exogenous adenosine
      5-triphosphate (ATP) but depressed KCl-induced contractions in a dose-related
      pattern; these two opposite actions might account for the lack of effect on field
      stimulation of the bladder purinergic nerves. The leaf extract depressed
      purinergic nerve-mediated contraction of the rat bladder in a dose-related
      fashion. This action could be attributed to blockade of purinergic
      neurotransmission since the leaf extract did not affect KCl-induced contractions.

PMID- 11295299
TI  - Antifertility studies of Colebrookia oppositifolia leaf extract in male rats with
      special reference to testicular cell population dynamics.
AB  - Oral feeding of male rats with the ethanolic leaf extract of Colebrookia
      oppositifolia at dose levels of 100 and 200 mg/kg for 8-10 weeks did not cause
      body weight loss, while the weights of testes and epididymides were significantly
      decreased. Seminal vesicles and ventral prostate showed a significant reduction
      at the higher dose only. Treated animals showed a notable depression of
      spermatogenesis. Following 100 and 200 mg/kg extract feeding, the preleptotene
      spermatocytes were decreased by 46.5 and 39.8%, the secondary spermatocytes by
      13.4 and 12.7%, the step-19 spermatids by 36.6 and 35.2%, and the mature Leydig
      cells by 31.2 and 39.5%, respectively. At both dose levels, the seminiferous
      tubule diameter, Leydig cells nuclear area and cytoplasmic area, as well as the
      cross-sectional surface area of Sertoli cells, were significantly reduced
      (P<0.001) when compared to controls. Reduced sperm count and motility resulted in
      100% negative fertility at 200 mg/kg dose level. A significant fall in the total
      protein and sialic acid content and acid phosphatase enzyme activity of the
      testes, epididymides, seminal vesicle and ventral prostate, as well as in the
      glycogen content of testes, was also observed at both dose levels in comparison
      with controls.

PMID- 11295300
TI  - Medicinal plants used for intestinal diseases in Mbalmayo region, Central
      Province, Cameroon.
AB  - Seventy-six plant species from 46 botanical families, traditionally used to treat
      intestinal diseases in Mbalmayo region are recorded. The local names and the way
      the plants are used are indicated.

PMID- 11295301
TI  - Antinociceptive effect of Elaeagnus angustifolia fruit seeds in mice.
AB  - The antinociceptive effect of different Elaeagnus angustifolia fruit seed
      extractives was studied in mice using hot-plate and writhing tests. Following
      intraperitoneal injection, the decoction (EaDE), the ethanol extract (EaEE), the
      aqueous and n-butanol fractions (EaAF, and EaBF, respectively) of a polyphenolic
      fraction, and two flavonoid-enriched fractions of EaBF (EaBCF1 and EaBCF2) showed
      significant antinociceptive activity in both tests, markedly and dose-dependently
      increasing the pain threshold.

PMID- 11295302
TI  - Isolation, purification and some structural features of the mucilaginous exudate
      from Musa paradisiaca.
AB  - The water-soluble polysaccharides isolated from the vascular gel of Musa
      paradisiaca, were fractionated via anion exchange chromatography into four
      fractions. Fractionated polymers contained arabinose, xylose and galacturonic
      acid as major sugars, together with traces of galactose, rhamnose, mannose and
      glucose residues. Methylation analysis revealed the presence of a highly branched
      arabinoxylan with a significant amount of terminal arabinopyranosyl units and an
      arabinogalactan type I pectin. Periodate oxidation studies supported the results
      of methylation analysis.

PMID- 11295303
TI  - Antioxidant and hepatoprotective effect of Acanthus ilicifolius.
AB  - The alcoholic extract of Acanthus ilicifolius leaves inhibited the formation of
      oxygen derived free radicals (ODFR) in vitro with IC(50) of 550 microg/ml, 2750
      microg/ml, 670 microg/ml and 600 microg/ml (Fe(2+)/ascorbate system), 980
      microg/ml (Fe(3+)/ADP/ascorbate system) for superoxide radical production,
      hydroxyl radical generation, nitric oxide radical formation and lipid peroxide
      formation, respectively. The oral administration of the extract (250 and 500
      mg/kg) significantly reduced CCl(4) induced hepatotoxicity in rats, as judged
      from the serum and tissue activity of marker enzymes [glutamate oxaloacetate
      transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline
      phosphatase (ALP)]. These results were comparable with those obtained with
      curcumin (100 mg/kg, p.o.).

PMID- 11295304
TI  - Antinociceptive activity of Malvastrum coromandelinum.
AB  - The aerial parts of Malvastrum coromandelinum showed antinociceptive activity in
      the 0.6% acetic acid-induced writhing test in mice, the effects of acetone
      extract (200 mg/kg, p.o.) being comparable with acetylsalicylic acid (100 mg/kg,
      p.o.)

PMID- 11295305
TI  - Antimicrobial activity of Omalanthus nervosus.
AB  - The ethanol extracts of Omalanthus nervosus leaves, stem and root barks, were
      partitioned (petrol, dichloromethane, ethyl acetate). In respect to crude
      extracts, all fractions demonstrated broader spectrum and higher levels of
      antibacterial activity, ethyl acetate fractions being in all cases the more
      active. No fraction was active against tested moulds.

PMID- 11295306
TI  - Mast cell stabilising activity of Bacopa monnieri.
AB  - Successive petroleum ether, chloroform, methanol and water extracts of Bacopa
      monnieri were tested (in vitro) for mast cell stabilising effect. The methanolic
      fraction exhibited potent activity comparable to disodium cromoglycate, a known
      mast cell stabiliser.

PMID- 11295307
TI  - Antimicrobial activity of Anacardium occidentale bark.
AB  - Anacardium occidentale bark 60% methanolic extract exhibited antimicrobial
      activity against 13 out of 15 bacterial isolates at a concentration of 20 mg/ml.

PMID- 11295308
TI  - An anti-inflammatory principle from cactus.
AB  - In previous studies, the ethanol extract of cactus (Opuntia ficus-indica) showed
      potent anti-inflammatory action. In the present study, following fractionation of
      the methanol extract of cactus stems guided by adjuvant-induced chronic
      inflammation model in mice, an active anti-inflammatory principle has been
      isolated and identified as beta-sitosterol.

PMID- 11295309
TI  - Antidiarrhoeal activity of root extracts from Roureopsis obliquifoliolata and
      Epinetrum villosum.
AB  - The methanol extracts of Roureopsis obliquifoliolata and Epinetrum villosum root
      significantly reduced castor oil-induced diarrhoea in mice. This effect supports
      the use of these plants in Congolese folk medicine as antidiarrhoeal remedies.

PMID- 11295310
TI  - Amoebicidal and giardicidal compounds from the leaves of Zanthoxylum
      liebmannianun.
AB  - The crude ethanol extract from the leaves of Zanthoxylum liebmannianum exhibited
      inhibitory effect on the reproduction of trophozoites of Entamoeba histolytica
      (IC(50)=3.48 microg/ml) and Giardia lamblia (IC(50)=58.00 microg/ml). From this
      extract, asarinin, hyperin, beta-sitosterol, and beta-sitosterol glucoside were
      isolated. Among them, asarinin was the most active with IC(50) values of 19.86
      microg/ml for E. histolytica and 35.45 microg/ml for G. lamblia. The remaining
      compounds showed moderate activity against both parasites.

PMID- 11295311
TI  - Antimicrobial activity of Harpullia ramiflora.
AB  - The methanol extracts of Harpullia ramiflora, leaves, flowers, stem and root
      barks were partitioned (petrol, dichloromethane, ethyl acetate). In respect to
      crude extracts, all fractions demonstrated broader spectrum and higher levels of
      antibacterial activity. The ethyl acetate fraction of the flowers exhibited the
      highest activity. No activity was shown against the tested moulds.

PMID- 11295312
TI  - Sorocein I, a new Diels-Alder type adduct from Sorocea ilicifolia.
AB  - From ethyl acetate extract of the root bark of Sorocea ilicifolia a new ketalized
      Diels-Alder type adduct, sorocein I (1), was isolated.

PMID- 11295313
TI  - A new phorbol diester from Aleurites moluccana.
AB  - A new phorbol diester, 13-O-myristyl-20-O-acetyl-12-deoxyphorbol (1), has been
      isolated from the benzene extract of the heartwood of Aleurites moluccana. In
      addition, hentriacontane, 6,7-dimethoxycoumarin, 5,6,7-trimethoxycoumarin and
      beta-sitostenone are being reported for the first time from this species.

PMID- 11295314
TI  - A new isoflavone from the roots of Asparagus racemosus.
AB  - The isolation and spectral data of a new isoflavone, 8-methoxy-5,6,4'
      trihydroxyisoflavone 7-O-beta-D-glucopyranoside (1), from the roots of Asparagus
      racemosus are reported.

PMID- 11295315
TI  - A new cardenolide from the seeds of Terminalia bellerica.
AB  - A new cardenolide, cannogenol 3-O-beta-D-galactopyranosyl-(1-->4)-O-alpha-L
      rhamnopyranoside (1), was isolated form the seeds of Teminalia bellerica.

PMID- 11295316
TI  - A new flavonoid from the aerial parts of Tridax procumbens.
AB  - A new flavonoid (procumbenetin), isolated from the aerial parts of Tridax
      procumbens, has been characterised as 3,6-dimethoxy-5,7,2',3',4'
      pentahydroxyflavone 7-O-beta-D-glucopyranoside (1) on the basis of spectroscopic
      techniques and by chemical means.

PMID- 11295317
TI  - Polyphenols from Eucalyptus ovata.
AB  - From the leaves of Eucalyptus ovata 13 known compounds, four flavonol glycosides
      and nine tannins, including the trimer gallocatechin-(4alpha-8)-gallocatechin
      (4alpha-8)-catechin (1), were isolated. The spectral data of the peracetate
      derivative of the trimer are reported.

PMID- 11295318
TI  - Coumarins from the aerial part of Halocnemum strobilaceum.
AB  - Four known coumarins, coumarin (1), 7-hydroxy-3-methylcoumarin (2), oreoselone
      (3) and heraclenin (4), were isolated from aerial part of Halocnemum
      strobilaceum. Their structures were determined by 1 and 2-D NMR techniques.

PMID- 11295319
TI  - Genes in drug abuse.
AB  - Because of the genome projects it will be possible to identify the changes in
      gene expression that are associated with drug abuse. The ultimate goal will be to
      determine the role and significance of the gene products. To date about 100 genes
      have been found with altered expression after administration of drugs. The
      development of new technologies such as microarrays will greatly facilitate
      finding such changes in expression. The rate at which levels of some gene
      products change is compatible with the time course of development of dependence
      in animals, but we must be able to establish a cause-effect relationship between
      genes and drug abuse, which this will be difficult. The product of the novel
      cocaine and amphetamine regulated transcript (CART) gene is a useful example
      where a gene product has been associated with drug abuse. CART was identified as
      an mRNA that changed in response to psychostimulant drug administration and
      injection of CART peptides into the ventral tegmental area produces
      psychostimulant-like effects. Definitive evidence, if obtainable, that specific
      genes are responsible for vulnerability to drug abuse could have dramatic effects
      on public health policy.

PMID- 11295320
TI  - Reducing the harms caused by cannabis use: the policy debate in Australia.
AB  - The debate about cannabis policy in Australia has revolved around the harms that
      cannabis causes to users and the community, on the one hand, and the harms that
      are caused by the prohibition of its use, on the other. This paper assesses
      evidence on: (1) the harms caused to users and the community by cannabis use
      (derived from the international scientific literature) and (2) the harms that
      arise from prohibition (as reflected in Australian research). The most probable
      harms caused by cannabis use include: an increased risk of motor vehicle
      accidents; respiratory disease; dependence; adverse effects on adolescent
      development; and the exacerbation of psychosis. The harms of the current
      prohibition on cannabis use policy are less tangible but probably include: the
      creation of a large blackmarket; disrespect for a widely broken law; harms to the
      reputation of the unlucky few cannabis users who are caught and prosecuted; lack
      of access to cannabis for medical uses; and an inefficient use of law enforcement
      resources. Cannabis policy unavoidably involves trade offs between competing
      values that should be made by the political process. Australian cannabis policy
      has converged on a solution which continues to prohibit cannabis but reduces the
      severity of penalties for cannabis use by either removing criminal penalties or
      diverting first time cannabis offenders into treatment and education.

PMID- 11295321
TI  - Correlates of initiation to cannabis use: a 5-year follow-up of 15-19-year-old
      adolescents.
AB  - Initiation to cannabis is often the first step in the use of illicit drugs. We
      studied the correlates of initiation in a 5-year follow-up study. A total of
      21.4% of the subjects reported using cannabis at some time. Of the 139 users,
      89.2% had tried cannabis not more than once or a few times. This initiation to
      cannabis was related to male gender, absence of mother, frequent lack of interest
      and early age at first sexual intercourse in logistic regression analysis. These
      factors seem to be useful in predicting initiation to cannabis.

PMID- 11295322
TI  - The effects of chronic morphine on behavior reinforced by several opioids or by
      cocaine in rhesus monkeys.
AB  - The reinforcing effects of intravenously delivered cocaine, alfentanil, morphine,
      heroin, nalbuphine, or buprenorphine were evaluated in four rhesus monkeys
      before, during, and after daily administration of 3.2 mg/kg morphine. Morphine
      was given 21 h prior to measures of the reinforcing effects of each of the drugs.
      No changes in the potency of cocaine or the high efficacy mu agonist alfentanil
      were detectable during the period of chronic morphine administration. Small (1/2
      1) log unit decreases in the reinforcing potency of intermediate efficacy mu
      agonists morphine and heroin occurred during chronic morphine administration.
      Larger decreases in both the potency and effectiveness of low-efficacy mu
      agonists nalbuphine and buprenorphine developed during this time. These data
      suggest that the amount of tolerance that develops to the reinforcing effects of
      opioids depends on the efficacy of the drugs used to maintain responding.

PMID- 11295323
TI  - How helpful are drug abuse helplines?
AB  - Raters called a convenience sample of 30 helplines and claimed to be alcohol,
      cocaine, heroin, marijuana or tobacco dependent persons seeking treatment.
      Responses were categorized as helpful, neutral or unhelpful. The median Kappa for
      agreement between pairs of raters rating a single call was 0.91. Between 36 and
      78% of the helplines gave inconsistent responses to two calls giving the same
      scenario. Across the 346 calls, 43, 40 and 40% of responses to alcohol, cocaine
      and heroin scenarios were helpful and 28 and 25% of responses to tobacco and
      marijuana calls were helpful. These preliminary results indicate that much of the
      time responses to calls to national helplines are not consistent and not helpful.

PMID- 11295324
TI  - Sensation seeking needs among 8th and 11th graders: characteristics associated
      with cigarette and marijuana use.
AB  - This cross-sectional school-based study explored the relationship between
      adolescent use of cigarettes and marijuana and the sensation seeking personality
      factors of (1) Disinhibition and (2) Thrill and Adventure Seeking. The study
      population included a representative sample of both male and female 8th and 11th
      graders in the state of Delaware. Analytic methods utilized included
      correlational analysis and multivariate logistic regression. In the multivariate
      logistic regression models, the Disinhibition personality factor accounted for
      cigarette and marijuana using behaviors with odds ratios ranging between 2 and 3.
      Thrill and Adventure Seeking was not a significant explanatory variable in any of
      the final multivariate models. Potential confounders (age, gender and race) were
      considered in all analyses. Of all the two-way interactions assessed, none was
      significant. The findings from this study utilizing a large general community
      sample indicate that sensation seeking needs are a potential risk factor for
      adolescent substance use.

PMID- 11295325
TI  - Alcohol expectancies and motives in a substance abusing male treatment sample.
AB  - Although prior research has demonstrated the utility of both alcohol expectancies
      and drinking motives in the prediction of alcohol use and problems, the specific
      relationship between these domains has not been examined in a clinical sample.
      One-hundred, forty-seven veterans on an inpatient substance abuse unit completed
      questionnaires measuring alcohol expectancies and alcohol motives and provided
      information on their alcohol consumption and related problems. Covariance
      structure modeling was used to test four theoretically competing models. Findings
      indicated that: (1) motives mediate the effects of expectancies on use and
      problems and expectancies do not exert an independent influence on consumption
      and alcohol problems and (2) contrary to past findings, alcohol use only
      partially mediates the relationship between enhancement motives and alcohol
      problems.

PMID- 11295326
TI  - Psychometric assessment of the Hallucinogen Rating Scale.
AB  - Reliability and convergent-discriminant validity of a Spanish version of the
      Hallucinogen Rating Scale (HRS) were assessed in two differentiated populations
      of hallucinogen users involving the retrospective assessment of drug effects. In
      Study 1 (immediate assessment), 75 European users of the South American
      hallucinogenic drink ayahuasca answered the HRS 4 h after drug intake in their
      habitual setting. In Study 2 (delayed assessment), 56 adult polydrug users
      answered the HRS and a short form of the Addiction Research Center Inventory
      (ARCI) recalling the effects they experienced when they last took a hallucinogen,
      in order to test the convergent-discriminant validity of HRS with the scales of
      the standard questionnaire used in most studies involving psychoactive drugs. The
      HRS scales showed increases after both the immediate and delayed retrospective
      assessment of drug effects. Reliability data indicated that four of the six
      scales show an acceptable level of internal consistency. Significant but limited
      correlations were found between the Perception and Somaesthesia scales and the
      ARCI LSD scale, pointing out the questionnaire's construct validity. Thus, the
      HRS was sensitive to hallucinogenic drug effects other than those elicited by
      intravenous N,N-dimethyltryptamine (DMT), for which it was originally designed,
      and showed reasonable reliability and convergent validity. Results suggest its
      usefulness in the evaluation of subjective effects elicited by psychoactive drugs
      with hallucinogenic properties, and constitute a preliminary approach to the
      effects of ayahuasca in European subjects.

PMID- 11295327
TI  - Factors associated with readiness to change drug use among needle-exchange users.
AB  - To determine if frequent needle-exchange program (NEP) use is associated with
      lower readiness to change drug use, NEP clients in Providence, RI were
      interviewed regarding their drug use, HIV risk, health, and past use of drug
      treatment services in 1997-1998. Readiness to change drug use was assessed using
      a nine-step decision ladder. Based on this assessment, 14.3% of the sample were
      classified as precontemplators (24/168), 29.2% were in the contemplation stage
      (49/168), and 56.5% were in the determination or ready to change stage (95/168).
      We found that mean number of NEP visits was 25.5 among precontemplators, 28.7
      among contemplators, and 22.5 among those in the determination stage. In
      multivariate analysis, an inverse relationship between having ever been in
      alcohol treatment and higher readiness to change drug use was the only
      significant association. In this exploratory study, we found that more frequent
      NEP participation did not impact readiness to change drug use among intravenous
      drug users. Given the high proportion of NEP clients ready to change drug use,
      improving linkages between NEPs and substance abuse treatment appears warranted.

PMID- 11295328
TI  - Drinking and driving: pre-driving attitudes and perceptions among Brazilian
      youth.
AB  - The aim of this study was to investigate driving under the influence of alcohol
      (DUI) risk profiles and predictors in a sample of pre-driving Brazilian youth, in
      the context of Brazil's new Traffic Code. Data were obtained in the Traffic
      Department in Sao Paulo from a sample of 2166 individuals. Subjects displayed a
      low level of knowledge about the laws and few believed the penalties would
      actually be enforced for those engaging in DUI. Findings suggest that changes in
      DUI laws in Brazil and elsewhere should be accompanied by enforcement and
      education in order to enhance levels of knowledge and credibility of the
      sanctions.

PMID- 11295329
TI  - Multiwave analysis of retest artifact in the National Longitudinal Survey of
      Youth drug use.
AB  - We examined follow-up data from surveys in 1988, 1992 and 1994 in order to
      estimate the prevalence and explore the correlates of retest artifact (denial) of
      drug use among National Longitudinal Survey of Youth respondents who disclosed
      lifetime cocaine or marijuana use in 1984. In the cocaine use cohort, 42% denied
      lifetime cocaine use during at least one follow-up wave. In the marijuana use
      cohort, about 29% denied lifetime marijuana use during at least one follow-up
      wave. Denial either leveled off (cocaine) or diminished (marijuana) between the
      second and third follow-up interviews. The most consistent predictors of denial
      in both longitudinal and cross-sectional models and across substances were
      race/ethnicity (black informants had increased rates of denial) and marital
      status (married respondents had increased rates of denial). Other predictors of
      denial included interviewer characteristics (social attribution), interview mode,
      and drug salience. The findings with respect to marijuana reporting trends
      parallel increased willingness of public officials to retrospectively disclose
      this behavior in the popular press.

PMID- 11295330
TI  - Outcomes after methadone maintenance and methadone reduction treatments: two-year
      follow-up results from the National Treatment Outcome Research Study.
AB  - This paper provides a detailed analysis of the 2-year outcomes for 351 drug
      misusers allocated on an intention-to-treat basis to methadone maintenance or
      methadone reduction treatments. Both groups showed substantial reductions in
      their use of illicit drugs and in other outcome areas. However, whereas most
      methadone maintenance patients received maintenance, only about one third of
      those allocated to methadone reduction received methadone reduction, and many
      actually received a form of methadone maintenance. Reduction patients were more
      likely to receive low doses of methadone, and were less likely to remain in
      treatment. For maintenance patients, higher doses and retention in treatment were
      both associated with improvements in illicit heroin use at 2 years. For the
      reduction patients, the more rapidly the methadone was reduced, the worse the
      heroin use outcomes. For patients in both treatment conditions, reductions in
      heroin use were associated with improvements in other outcome areas. The more
      severely dependent patients showed better outcomes in methadone maintenance.
      Methadone reduction treatment processes were associated with poor outcomes, and
      many patients who were allocated to methadone reduction treatment did not receive
      reduction treatment as intended. This calls into question the appropriateness of
      either the initial treatment planning process or the treatment delivery process,
      or both. A clearer distinction should be made between methadone maintenance and
      methadone reduction. Treatment goals should be made explicit both to the patient
      and to the clinical staff at the start of treatment. We suggest the need for a
      reappraisal of the goals and procedures of methadone reduction treatment.

PMID- 11295331
TI  - A prime-boost vaccination strategy using naked DNA followed by recombinant
      porcine adenovirus protects pigs from classical swine fever.
AB  - Weaned pigs (6-week-old) and 7-day-old pre-weaned piglets were vaccinated with
      naked plasmid DNA expressing the gp55/E2 gene from classical swine fever virus
      (CSFV). Both groups of pigs were then given a booster dose of recombinant porcine
      adenovirus expressing the gp55 gene (rPAV-gp55). Following challenge with CSFV,
      100% of weaned pigs and 75% pre-weaned piglets were protected from disease.
      Weaned pigs given a single dose of rPAV-gp55 were also protected, but showed a
      slight increase in temperature immediately post-challenge. However, weaned
      animals given a DNA prime before rPAV-gp55 showed no fluctuation in body
      temperature following challenge and no pathology in spleen or lymph nodes upon
      post-mortem. In addition, no CSFV could be re-isolated from the rPAV vaccinated
      group and from only one pig in the prime-boost group following challenge,
      suggesting that both vaccination regimes have the potential to reduce or prevent
      virus shedding following experimental challenge.

PMID- 11295332
TI  - A physical map of the Mycoplasma agalactiae strain PG2 genome.
AB  - We have constructed a physical map of the Mycoplasma agalactiae strain PG2
      chromosome analyzing it by pulsed field gel electrophoresis in a contour-clamped
      homogeneous electric-field system. We mapped 33 cleavage sites generated with
      SmaI, XhoI, SalI, EclXI and BsiWI restriction endonucleases using double
      digestions, one- and two-dimensional pulsed electrophoresis, cross-hybridization
      and linking clones. We have also mapped the loci of some genes by Southern
      hybridization.

PMID- 11295333
TI  - Staphylococcus aureus associated with mammary glands of cows: genotyping to
      distinguish different strains among herds.
AB  - The hypothesis that strains of Staphylococcus aureus are more likely to be unique
      to a herd than common to several herds was tested. Herds (n=28) from nine
      geographic areas of Korea, with elevated milk somatic cell counts (>500000
      cells/ml) were enrolled in this study. Mammary quarter milk samples were
      aseptically collected from all lactating cows (n=616) with at least three
      functional quarters. Milk was cultured and S. aureus isolates were typed using
      pulse field gel electrophoresis of DNA SmaI digests. A total of 181 cows were
      identified as having S. aureus intramammary infections. A total of 52 different
      types of S. aureus were identified and 34 (65.4%) were associated with a single
      herd. A total of 18 types of S. aureus were found in multiple herds; 14 types
      were found in two herds, and four types were found in three herds. Herds with 1,
      2, 3, and more than 3 types, were: four (14.3%); eight (28.6%); nine (32.1%); and
      seven (25.0%). The data indicate that the majority of strains were found in one
      herd only, and more than 90% were found in two or less herds, suggesting that
      strains of S. aureus are more likely to be restricted to a single herd, than
      found in multiple herds.

PMID- 11295335
TI  - Rapid and accurate typing of Dichelobacter nodosus using PCR amplification and
      reverse dot-blot hybridisation.
AB  - Here we describe an approach to genotyping D. nodosus, based on variation in the
      fimbrial subunit gene (fimA), which uses polymerase chain reaction (PCR)
      amplification and hybridisation to immobilised oligonucleotides
      (PCR/oligotyping). The variable region of D. nodosus fimA, amplified and labelled
      with digoxigenin (DIG) in a single multiplex PCR amplification, was hybridised to
      a panel of group- and type-specific poly-dT tailed oligonucleotides that were
      immobilised on a nylon membrane strip. A mixture of positive control poly-dT
      tailed oligonucleotides was also included on the membrane. After hybridisation
      the membrane was washed to a defined specificity, and DIG-labelled fragments
      hybridising were detected with nitroblue tetrazolium (NBT) and 5-bromo-4-chloro-3
      indolyl phosphate (SCIP). The specificity of the oligonucleotides was verified by
      the lack of cross-reactivity with D. nodosus fimA sequences that had a single
      base difference. DNA from 14 footrot samples previously genotyped by PCR
      SSCP/sequencing [Vet. Microbiol. 71 (2000) 113], was assayed using the
      PCR/oligotyping technique. All types of D. nodosus which had been detected
      previously with a PCR-SSCP/sequencing method were detected by this procedure.
      However, for three of the 14 footrot samples, PCR/oligotyping detected additional
      types of D. nodosus. Further PCR amplification using type-specific primers,
      confirmed that these types of the bacterium were present in the footrot samples.
      These results indicate that PCR/oligotyping is a specific, accurate, and useful
      tool for typing footrot samples. In combination with a rapid DNA extraction
      protocol, D. nodosus strains present in a footrot sample can be accurately
      identified in less than 2 days.

PMID- 11295334
TI  - Typing of Salmonella enterica subsp. enterica serovar Mbandaka isolates.
AB  - Recently, Salmonella enterica subsp. enterica serovar Mbandaka (S. Mbandaka) has
      gained some importance in the epidemiology of salmonellosis in Poland. Since
      biotyping, resistance typing, and plasmid profiling were insufficient for strain
      differentiation, genome macrorestriction by means of pulse-field gel
      electrophoresis (PFGE) was applied and proved to be the method of choice in S.
      Mbandaka epidemiological studies. XbaI and BcuI macrorestriction produced 15 and
      14 pulse-field profiles (PFP), respectively, but in the case of each enzyme one
      profile was prevalent. When macrorestriction profiles were combined, a total 24
      patterns were found. Based on the similarity of the profiles, four clonal
      lineages were identified. One clonal lineage contained the majority of poultry,
      feed and human isolates. Poultry was concluded to be an important source of S.
      Mbandaka for humans in Poland. Complementary use of various typing techniques
      improved efficacy of epidemiological studies giving possibility to subdivide S.
      Mbandaka into 35 types and the index of discrimination reached 0.947.

PMID- 11295336
TI  - Fluorescence polarization assay for the diagnosis of bovine brucellosis:
      adaptation to field use.
AB  - A fluorescence polarization assay (FPA) was used to test whole blood samples
      prepared by mixing blood cells from cattle without exposure to Brucella abortus
      (B. abortus) with sera from animals with confirmed (bacteriologically) infection.
      A cut-off value between negative and positive values was initially established to
      be 87.2mP. This value was changed to 95mP to increase assay specificity without
      loss of sensitivity when testing blood samples from negative animals. The FPA
      technology was applied to whole blood samples in the field and to stored whole
      blood samples using two diluent buffers. Relative sensitivity and specificity
      values for the FPA performed in the field, based on buffered antigen plate
      agglutination test and competitive enzyme immunoassay results were 95.3 and
      97.3%, respectively. However, to obtain maximum sensitivity and specificity, a
      cut-off value of 105mP was determined for fresh whole blood samples. The relative
      sensitivity and specificity values of the FPA when testing stored whole blood
      samples were 100% each using a 95mP cut-off.The usefulness of the FPA for testing
      whole blood samples in the field was demonstrated.

PMID- 11295337
TI  - Salmonella seroprevalence at the population and herd level in pigs in The
      Netherlands.
AB  - The aim of this study was to provide baseline data on the population and herd
      Salmonella seroprevalence in sows and finishers. For the population estimates in
      1996 and 1999 and the herd prevalences for sows and gilts, blood samples from
      swine vesicular disease (SVD) and pseudorabies monitoring programmes were used
      and tested in an indirect Salmonella enzyme-linked immunosorbent assay (ELISA).
      The herd prevalence for finishers was determined using blood samples collected at
      two slaughterhouses. The population prevalence for finishers in 1996 and 1999 was
      23.7 and 24.5%, respectively, and for sows 40.5 and 60.4%, respectively. The
      prevalence in free range (FR) finishers was significantly higher (44.6%) than in
      intensively housed finishers in 1999, identifying a hazard group for possible
      extra pork and pork product contamination. Of 406 finishing herds, 9% were
      completely seronegative for Salmonella (cut-off OD%>10). Of these 406 finishing
      herds, 69.7% had Salmonella-status I (low prevalence), 21.7% status II (moderate
      prevalence) and 8.6% status III (high prevalence) (cut-off OD%>40). In 46
      multiplying sow herds, 20 breeding sow herds and 20 matching replacement gilt
      herds, the average herd prevalences were 54, 44.4 and 19.3%, respectively. Two
      gilt herds were completely seronegative. The prevalence in the gilt herds was
      never higher than in the matching breeding sow herds. Agreement on methodology
      and calibration of ELISA tests would make these results comparable between
      countries and is a prerequisite for a co-ordinated and integrated program to
      reduce Salmonella in pork in the European Union.

PMID- 11295338
TI  - Epidemiology of Bartonella infection in domestic cats in France.
AB  - Blood samples were collected between February and June 1996 from a convenience
      sample of 436 domestic French cats living in Paris and its environs and were
      tested for Bartonella bacteremia and seropositivity. Seventy-two cats (16.5%)
      were Bartonella bacteremic, of which 36 cats (50%) were infected with Bartonella
      henselae type II (B.h. II) only, 15 cats (21%) were infected with Bartonella
      clarridgeiae (B.c.) only, and 11 cats (15%) were infected with B. henselae type I
      (B.h. I) only. Eight cats (11%) were co-infected with B. henselae and B.
      clarridgeiae (B.h. II/B.c.: five cats; B.h. I/B.c.: three cats). Two cats (2.8%)
      were concurrently bacteremic with B. henselae types I and II. Risk factors
      associated with bacteremia included ownership for <6months (prevalence ratio
      (PR)=1.80; 95% confidence interval (CI)=1.13-2.85), adoption from the pound or
      found as a stray (PR=1.67, 95% CI=1.05-2.65), and cohabitation with one or more
      cats (PR=1.60, 95% CI=1.01-2.53). Bartonella antibodies to either B. henselae or
      B. clarridgeiae were detected in 179 cats (41.1%). Risk factors associated with
      seroposivity paralleled those for bacteremia, except for lack of association with
      time of ownership. Prevalence ratios of bacteremic or seropositive cats increased
      with the number of cats per household (p=0.02). The lack of antibodies to B.
      henselae or B. clarridgeiae was highly predictive of the absence of bacteremia
      (predictive value of a negative test=97.3%). Multiple logistic regression
      analysis indicated that bacteremia, after adjustment for age and flea
      infestation, and positive serology, after adjustment for age, were associated
      with origin of adoption and number of cats in the household. Flea infestation was
      associated with positive serology.

PMID- 11295339
TI  - Neonatal auditory activation detected by functional magnetic resonance imaging.
AB  - The objective of this study was to detect auditory cortical activation in non
      sedated neonates employing functional magnetic resonance imaging (fMRI). Using
      echo-planar functional brain imaging, subjects were presented with a frequency
      modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices
      running parallel to the superior temporal gyrus. Twenty healthy neonates (13
      term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level
      dependent (BOLD) signal in response to auditory stimulus was detected in all 4
      adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated
      increased signal in the superior temporal regions during auditory stimulation. In
      contrast, signal decreases were detected during auditory stimulation in 9 of 14
      newborns with BOLD response. fMRI can be used to detect brain activation with
      auditory stimulation in human infants.

PMID- 11295340
TI  - Increasing mean airway pressure reduces functional MRI (fMRI) signal in the
      primary visual cortex.
AB  - Changes in both blood flow and blood oxygenation determine the functional MRI
      (fMRI) signal. In the present study factors responsible for blood oxygenation
      (e.g., FiO(2)) were held constant so that changes in pixel count would above all
      reflect changes in regional cerebral blood flow (rCBF). Continuous positive
      airway pressure (CPAP) breathing at 12 cm H(2)O, which was previously shown to
      influence rCBF, was applied in human volunteers (n = 19) to investigate the
      sensitivity of fMRI for changes in rCBF caused by increased mean airway pressure.
      Increasing the mean airway pressure decreased the pixel count in the primary
      visual cortex (median (range)): baseline: 219 (58-425) pixels vs. CPAP (12 cm
      H(2)O): 92 (0-262) pixels). These findings indicate that fMRI is sensitive to
      detect a reduced rCBF-response in the primary visual cortex. The underlying
      mechanism is likely to be a reduced basal rCBF due to constriction and/or
      compression of postcapillary venoles during CPAP breathing. These findings are
      important for interpreting fMRI results in awake and in artificially respirated
      patients, in whom positive airway pressure is used to improve pulmonary function
      during the diagnostic procedure.

PMID- 11295341
TI  - Assessment of cerebrovascular reactivity with functional magnetic resonance
      imaging: comparison of CO(2) and breath holding.
AB  - Cerebral blood flow (CBF) and oxygenation changes following both a simple breath
      holding test (BHT) and a CO(2) challenge can be detected with functional magnetic
      resonance imaging techniques. The BHT has the advantage of not requiring a source
      of CO(2) and acetazolamide and therefore it can easily be performed during a
      routine MR examination. In this study we compared global hemodynamic changes
      induced by breath holding and CO(2) inhalation with blood oxygenation level
      dependent (BOLD) and CBF sensitized fMRI techniques. During each vascular
      challenge BOLD and CBF signals were determined simultaneously with a combined
      BOLD and flow-sensitive alternating inversion recovery (FAIR) pulse sequence.
      There was a good correlation between the global BOLD signal intensity changes
      during breath holding and CO(2) inhalation supporting the notion that the BHT is
      equivalent to CO(2) inhalation in evaluating the hemodynamic reserve capacity
      with BOLD fMRI. In contrast, there was no correlation between relative CBF
      changes during both vascular challenges, which was probably due to the reduced
      temporal resolution of the combined BOLD and FAIR pulse sequence.

PMID- 11295342
TI  - Rate dependence of human visual cortical response due to brief stimulation: an
      event-related fMRI study.
AB  - The human brain response to a wide range of visual stimulus rates presented over
      a prolonged time period has been investigated by various neuroimaging techniques.
      However, to date, no imaging study has been performed to study the dynamic human
      brain response to various stimulus rates when presented in a short time. This
      report describes activation in the human brain due to brief visual stimulus
      presentation (1 s) for stimulus rates varying from 1 to 20 Hz using event-related
      functional MRI (fMRI). Our results show that the amplitude of the fMRI response
      increases with the stimulus frequency and plateaus at 6 Hz. This finding differs
      slightly from the results of previous blocked task paradigm experiments (with a
      longer time of stimulus presentation), in which the response peaks at
      approximately 8 Hz and then decreases. Our results are in close agreement with
      previously published psychophysical studies, suggesting that the fMRI signal in
      this experiment is indicative of cortical activity related to visual processing.

PMID- 11295343
TI  - Functional MRI of motor and sensory activation in the human spinal cord.
AB  - MR imaging of the cervical spinal cord was carried out on volunteers during
      alternated rest and either motor or sensory stimulation of one hand, in order to
      detect image intensity changes arising concomitant to neuronal activity. We
      employed both spin-echo and gradient-echo echo-planar imaging, on the right and
      left hands, with both symmetric and asymmetric temporal patterns of rest and
      stimulation. Intensity changes correlated with the time course of stimulation
      were consistently detected, and the magnitude of the intensity changes depended
      on the duration of stimulation. The activated regions in the spinal cord extended
      along a column on the side of the body being stimulated and included localized
      regions on the contralateral side, in agreement with the neural anatomy.

PMID- 11295344
TI  - Enhanced sensitivity to molecular diffusion with intermolecular double-quantum
      coherences: implications and potential applications.
AB  - Apparent molecular self-diffusion rates for (1)H intermolecular double-quantum
      coherences (iDQCs) were measured in solvents covering a wide range of intrinsic
      diffusion coefficients at 1.5, 9.4 and 14T, and water iDQC diffusion-weighted
      images were obtained at 1.5T in human brains and at 9.4T in rat brains.
      Conventional single quantum coherence (SQC) measurements were also made in the
      same samples. Experimental results indicate that iDQCs are approximately twice as
      sensitive to diffusion as SQC. A general theoretical expression was derived, and
      a model was proposed to explain the phenomenon. Potential applications in DWI and
      brain fMRI were also discussed.

PMID- 11295345
TI  - Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury:
      differential diagnosis with MR imaging.
AB  - The objective of this study was to assess the value of MR imaging in the
      differentiation between a recurrent hepatocellular carcinoma (HCC) and a
      radiation-induced hepatic injury. Nine male patients with suspected recurrence
      after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA
      enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)
      weighted images (WI) and the relative enhancement of the dynamic study were
      calculated. Recurrent tumors and the irradiated area showed similar image
      characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values
      and signal intensity ratios in the T(1)-WI were not significantly different. In
      the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement,
      followed by a rapid washout. However, the irradiated liver parenchyma showed
      hyperintensity from an early phase, and contrast enhancement tended to be more
      prominent and prolonged at the end of the dynamic studies. The characteristic
      findings of the dynamic MR study enable us to distinguish between a recurrent HCC
      and a radiation-induced hepatic injury.

PMID- 11295346
TI  - Early MRI findings of rapidly destructive coxopathy.
AB  - To diagnose rapidly destructive coxopathy (RDC) in its early stages and
      understand the pathomechanism of associated joint destruction, ten cases of RDC
      were followed by periodic MRI from onset of the disease. In the initial stage
      (stage 1) of RDC, when radiographs revealed slight narrowing of the joint space,
      a small subchondral area of low signal intensity was observed on T(1)-weighted
      images (T1WI) and inhomogeneous high intensity was observed on T(2)-weighted
      images (T2WI) in the antero-lateral portion of the femoral head. When radiographs
      showed obliteration of the joint space (stage 2), MRI revealed a diffuse area of
      low intensity on TIWI and high intensity on T2WI in the proximal femur, including
      the femoral neck and head, suggesting extensive bone marrow edema. The femoral
      head and acetabulum were aggressively destroyed (stage 3) in all cases 3 to 6
      months after the diffuse abnormal pattern was observed on MRI. MRI in stage 3
      cases showed low intensity areas on both T1WI and T2WI. RDC did not show the band
      like pattern of low intensity on T1WI and high intensity on T2WI that typify MRI
      findings in cases of osteonecrosis. When joint space narrowing is observed
      radiographically, the diffuse abnormal pattern of low intensity on T1WI and high
      intensity on T2WI induced by a subchondral small lesion might be an early sign of
      RDC.

PMID- 11295347
TI  - Classification of signal-time curves from dynamic MR mammography by neural
      networks.
AB  - The aim of this study was to test the performance of artificial neural networks
      for the classification of signal-time curves obtained from breast masses by
      dynamic MRI. Signal-time courses from 105 parenchyma, 162 malignant, and 102
      benign tissue regions were examined. The latter two groups were
      histopathologically verified. Four neural networks corresponding to different
      temporal resolutions of the signal-time curves were tested. The resolution ranges
      from 28 measurements with a temporal spacing of 23s to just 3 measurements taken
      1.8, 3, and 10 minutes after contrast medium administration. Discrimination
      between malignant and benign lesions is best if 28 measurement points are used
      (sensitivity: 84%, specificity: 81%). The use of three measurement points results
      in 78% sensitivity and 76% specificity. These results correspond to values
      obtained by human experts who visually evaluated signal-time curves without
      considering additional morphologic information. All examined networks yielded
      poor results for the subclassification of the benign lesions into fibroadenomas
      and benign proliferative changes. Neural networks can computationally fast
      distinguish between malignant and benign lesions even when only a few post
      contrast measurements are made. More precise specification of the type of the
      benign lesion will require incorporation of additional morphological or
      pharmacokinetic information.

PMID- 11295348
TI  - Adaptive data acquisition in MRI.
AB  - We propose an adaptive data acquisition technique that depends on the object to
      be imaged in magnetic resonance (MR) imaging. In this paper, we employed a
      matching pursuit (MP) algorithm to achieve the adaptive data acquisition. Since
      the matching pursuit is a greedy algorithm to find RF and gradient waveforms
      which are the best match for an object-signal, the signal can be decomposed with
      a few iterations and thereby lead reduction of imaging time in MR. To adopt the
      matching pursuit algorithm to the adaptive data acquisition in MRI, we have
      designed a dictionary which contains a windowed Fourier basis set. Because the
      basis set is localized spatially, the image signal could be divided into
      segmented signals so that matching pursuit with the segmented signals could lead
      to effective and object-dependent data acquisition. To verify the proposed
      technique, computer simulations and experiments are performed with a 1.0 T whole
      body MRI system.

PMID- 11295349
TI  - Three-dimensional segmentation of anatomical structures in MR images on large
      data bases.
AB  - In this paper an image-based method founded on mathematical morphology is
      presented in order to facilitate the segmentation of cerebral structures over
      large data bases of 3D magnetic resonance images (MRIs). The segmentation is
      described as an immersion simulation, applied to the modified gradient image,
      modeled by a generated 3D-region adjacency graph (RAG). The segmentation relies
      on two main processes: homotopy modification and contour decision. The first one
      is achieved by a marker extraction stage where homogeneous 3D-regions are
      identified. This stage uses contrasted regions from morphological reconstruction
      and labeled flat regions constrained by the RAG. Then, the decision stage intends
      to precisely locate the contours of regions detected by the marker extraction.
      This decision is performed by a 3D extension of the watershed transform. The
      method has been applied on a data base of 3D brain MRIs composed of fifty
      patients. Results are illustrated by segmenting the ventricles, corpus callosum,
      cerebellum, hippocampus, pons, medulla and midbrain on our data base and the
      approach is validated on two phantom 3D MRIs.

PMID- 11295350
TI  - Three-dimensional magnetic resonance spectroscopic imaging of histologically
      confirmed brain tumors.
AB  - The goal of this study was to determine whether presurgical metabolite levels
      measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable
      cancer within human brain tumor masses. A total of 31 patients (33 exams, 39
      pathology correlations) with brain tumors were studied prior to surgical biopsy
      and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1
      cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI
      localization. Levels of choline, creatine and NAA were estimated from the
      locations of the resected tissue and normalized to normal appearing brain tissue.
      The data were correlated with subsequent histologic analysis of the biopsy tissue
      samples. Although there were large variations in the metabolite ratios, all
      regions of confirmed cancer demonstrated significant choline levels and a mean
      choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest
      value is greater than 4 standard deviations above the mean (0.52 +/- 0.13) found
      in 8 normal volunteers. The choline signal intensities in confirmed cancers were
      significantly elevated compared to normal appearing brain tissue with a mean
      ratio of 1.71 +/- 0.69. Spectra with no significant metabolite levels were
      observed in the non-enhancing necrotic core of the tumor masses. The results of
      this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite
      levels in regions of viable cancer and grades and can differentiate cancer from
      necrosis and/or normal brain tissue.

PMID- 11295351
TI  - Prospective evaluation of in vivo proton MR spectroscopy in differentiation of
      similar appearing intracranial cystic lesions.
AB  - Proton MR spectroscopy (PMRS) has been found to be useful in differentiating
      various cystic intracranial lesions. The purpose of the present study was to
      prospectively evaluate the spectral pattern of various cystic lesions of brain
      with similar imaging appearances and to determine the accuracy of this technique
      in the differential diagnosis of these lesions. Fifty-one patients with
      intracranial cystic lesions (21 abscesses, 20 gliomas, 3 hydatid cysts, 3
      arachnoid cysts, 1 case each of glioependymal cyst, xanthogranuloma, infarction
      and acoustic neuroma) were evaluated with conventional MR imaging and in vivo
      PMRS. Ex vivo PMRS of the cystic contents aspirated at surgery in 31 cases was
      also done to confirm the in-vivo results. Preoperative diagnosis of the lesions
      was based on the results of in vivo PMRS. In vivo PMRS accurately predicted the
      pathology in 92% of the cases. We conclude that in-vivo PMRS complements imaging
      in better characterization of cystic intracranial mass lesions.

PMID- 11295352
TI  - RF coils for combined MR and hyperthermia studies: I. Hyperthermia applicator as
      an MR coil.
AB  - Combining hyperthermia, an experimental/adjuvant therapeutic modality for cancer,
      with the non-invasive metabolic studies using Magnetic Resonance (MR) is an
      interesting area of research. This two parts article discusses the development
      and testing of a conventional RF hyperthermia applicator for MR studies and vice
      versa. In this first part, an inductive type applicator known as 'Magnetrode' in
      RF hyperthermia has been used both as an MR volume resonator and a surface coil.
      Its concurrent performance as an hyperthermic applicator and an MR
      transmit/receive coil has been evaluated.

PMID- 11295353
TI  - RF coils for combined MR and hyperthermia studies: II. MR coil as an hyperthermic
      applicator.
AB  - Single loop surface coil, often used in MR studies, was evaluated for its
      performance as an inductive hyperthermic applicator. The heat deposition pattern
      produced by the surface coil at 84 MHz and 34 MHz was mapped in muscle-mimicking
      agar phantoms. Temperatures were measured simultaneously at 64 points using
      multiple-junction thermocouples.

PMID- 11295354
TI  - Assessment of scanner performance and normalization of estimated relaxation rate
      values.
AB  - The purpose of this study was to develop and test a method for the assessment of
      Magnetic Resonance (MR) scanner performance suitable for routine brain MR studies
      and for normalization of calculated relaxation times. We hypothesized that
      regular monitoring of machine performance changes could provide a helpful
      normalization tool for calculating tissue MR parameters, thus contributing to
      support their use for longitudinal and comparative studies of both normal and
      diseased tissues. The method is based on the acquisition of phantom images during
      routine brain studies with standard spin-echo sequences. MR phantom and brain
      tissue parameters were used to assess the influence of machine related changes on
      relaxation parameter estimates. Experimental results showed that scanner
      performance may affect relaxation rate estimates. Phantom and in vivo results
      indicate that the correction method yields a reduction in variability of
      estimated phantom R1 values up to 29% and of R1 for different brain structures up
      to 17%. These findings support the validity of using brain coil phantoms for
      routine system monitoring and correction of tissue relaxation rates.

PMID- 11295355
TI  - Gemcitabine-associated posterior reversible encephalopathy syndrome: MR imaging
      and MR spectroscopy findings.
AB  - A 55 year old female receiving gemcitabine for stage IV non-small cell carcinoma
      of the lung developed the clinical-radiologic syndrome of posterior reversible
      encephalopathy syndrome (PRES). She had clinical manifestations of headaches,
      increasing somnolence and tonic-clonic seizures. The fluid-attentuated inversion
      recovery (FLAIR) MR imaging sequence conspicuously showed bihemispheric,
      symmetrical cortical and subcortical white matter hyperintensities that
      preponderantly involved the parietal and occipital lobes. Diffusion-weighted
      imaging (DWI) sequence reflected the preponderant existence of vasogenic edema in
      the involved areas. MR spectroscopy showed no significant N-acetyl aspartate
      (NAA) depletion or lactate elevation prospectively, indicating the absence of
      significant neuronal loss and reversibility of the brain parenchymal changes. The
      clinical and radiologic manifestations essentially resolved completely with
      discontinuation of the drug.

PMID- 11295356
TI  - A possible emerging role of phytochemicals in improving age-related neurological
      dysfunctions: a multiplicity of effects.
AB  - It is rare to see a day pass in which we are not told through some popular medium
      that the population is becoming older. Along with this information comes the
      "new" revelation that as we enter the next millennium there will be increases in
      age-associated diseases (e.g., cancer, cardiovascular disease) including the most
      devastating of these, which involve the nervous system (e.g., Alzheimer's disease
      [AD] and Parkinson's disease [PD]). It is estimated that within the next 50 years
      approximately 30% of the population will be aged 65 years or older. Of those
      between 75 and 84 years of age, 6 million will exhibit some form of AD symptoms,
      and of those older than 85 years, over 12 million will have some form of dementia
      associated with AD. What appears more ominous is that many cognitive changes
      occur even in the absence of specific age-related neurodegenerative diseases.
      Common components thought to contribute to the manifestation of these disorders
      and normal age-related declines in brain performance are increased susceptibility
      to long-term effects of oxidative stress (OS) and inflammatory insults. Unless
      some means is found to reduce these age-related decrements in neuronal function,
      health care costs will continue to rise exponentially. Thus, it is extremely
      important to explore methods to retard or reverse age-related neuronal deficits
      as well as their subsequent, behavioral manifestations. Fortunately, the growth
      of knowledge in the biochemistry of cell viability has opened new avenues of
      research focused at identifying new therapeutic agents that could potentially
      disrupt the perpetual cycle of events involved in the decrements associated with
      these detrimental processes. In this regard, a new role in which certain dietary
      components may play important roles in alleviating certain disorders are
      beginning to receive increased attention, in particular those involving
      phytochemicals found in fruits and vegetables.

PMID- 11295357
TI  - Possible antioxidant mechanism in melatonin reversal of aging and chronic ethanol
      induced amnesia in plus-maze and passive avoidance memory tasks.
AB  - Cognitive dysfunction is one of the most striking age-related impairments seen in
      human beings and animals. This impairment probably is due to the vulnerability of
      the brain cells to increased oxidative stress during aging process. Pineal
      hormone melatonin is reported to be an endogenous antioxidant, whose peak plasma
      level declines during aging and in Alzheimer's disease (AD). Present experiments
      were performed to study the possible effect of exogenously administered melatonin
      on cognitive performance of young, aged, or ethanol-intoxicated mice (an animal
      model for AD) using one trial step-down type of passive avoidance and elevated
      plus-maze task. Aged or chronic ethanol-treated mice showed poor retention of
      memory in step-down passive avoidance and in elevated plus-maze task. Chronic
      administration of melatonin (0.1-10 mg/kg, sc) for 30 d or its coadministration
      with ethanol (15% W/V, 2 g/kg perorally) for 24 d significantly reversed the age
      induced or chronic ethanol-induced retention deficits in both the test paradigms.
      However, in both the memory paradigms chronic administration of melatonin failed
      to modulate the retention performance of young mice. Chronic administration of
      melatonin (0.1-10 mg/kg) for 30 d also reversed age-associated decline in
      forebrain total glutathione (tGSH) level. Chronic ethanol administration to young
      mice produced decline in forebrain tGSH level and enhanced brain lipid
      peroxidation, which was significantly reversed by coadministration of melatonin
      (10 mg/kg). The results of this study showed chronic melatonin treatment reverses
      cognitive deficits in aged and ethanol-intoxicated mice, which is associated with
      its antioxidant property.

PMID- 11295358
TI  - Electron spin resonance characterization of the NAD(P)H oxidase in vascular
      smooth muscle cells.
AB  - Endogenously produced reactive oxygen species are important for intracellular
      signaling mechanisms leading to vascular smooth muscle cell (VSMC) growth. It is
      therefore critical to define the potential enzymatic sources of ROS and their
      regulation by agonists in VSMCs. Previous studies have investigated O2*-
      production using lucigenin-enhanced chemiluminescence. However, lucigenin has
      been recently criticized for its ability to redox cycle and its propensity to
      measure cellular reductase activity independent from O2*-. To perform a
      definitive characterization of VSMC oxidase activity, we used electron spin
      resonance trapping of O2*- with DEPMPO. We confirmed that the main source of O2*-
      from VSMC membranes is an NAD(P)H oxidase and that the O2*- formation from
      mitochondria, xanthine oxidase, arachidonate-derived enzymes, and nitric oxide
      synthases in VSMC membranes was minor. The VSMC NAD(P)H oxidase(s) are able to
      produce more O2*- when NADPH is used as the substrate compared to NADH (the
      maximal NADPH signal is 2.4- +/- 0.4-fold higher than the NADH signal). The two
      substrates had similar EC(50)'s ( approximately 10-50 microM). Stimulation with
      angiotensin II and platelet-derived growth factor also predominantly increased
      the NADPH-driven signal (101 +/- 8% and 83 +/- 1% increase above control,
      respectively), with less of an effect on NADH-dependent O2*- (17 +/- 3% and 36 +/
      5% increase, respectively). Moreover, incubation of the cells with diphenylene
      iodonium inhibited predominantly NADPH-stimulated O2*-. In conclusion, electron
      spin resonance characterization of VSMC oxidase activity supports a major role
      for an NAD(P)H oxidase in O2*- production in VSMCs, and provides new evidence
      concerning the substrate dependency and agonist-stimulated activity of this key
      enzyme.

PMID- 11295359
TI  - Protein and DNA oxidation in spinal injury: neurofilaments--an oxidation target.
AB  - This study measured the time courses of protein and DNA oxidation following
      spinal cord injury (SCI) in rats and characterized oxidative degradation of
      proteins. Protein carbonyl content-a marker of protein oxidation-significantly
      increased at 3-9 h postinjury and the ratio 8-hydroxy-2
      deoxyguanosine/deoxyguanosine-an indicator of DNA oxidation-was significantly
      higher at 3-6 h postinjury in the injured cords than in the sham controls. This
      suggests that oxidative modification of proteins and DNA contributes to secondary
      damage in SCI. Densities of selected bands on coomassie-stained gels indicated
      that most proteins were degraded. Neurofilament protein (NFP) was particularly
      evaluated immunohistochemically; its light chain (NFP-68) was gradually degraded
      in nerve fibers, neuron bodies, and large dendrites following SCI. A mixture of
      Mn (III) tetrakis (4-benzoic acid) porphyrin (10 mg/kg)-a novel SOD mimetic-and
      nitro-L-arginine (1 mg/kg)-an inhibitor of nitric oxide synthase-injected
      intraperitoneally, increased NFP-68 immunoreactivity and the numbers of NFP
      positive nerve fibers post-SCI, correlating NFP degradation in SCI to free
      radical-triggered oxidative damage for the first time. Therefore, blockage of
      protein and DNA oxidation in the secondary injury stage may improve long-term
      recovery-important information for development of the SCI therapies.

PMID- 11295360
TI  - Variants of peroxiredoxins expression in response to hydroperoxide stress.
AB  - We examined patterns of the proteins that were expressed in human umbilical vein
      endothelial cells (HUVEC) in response to oxidative stress by two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE). When HUVEC were exposed to H2O2 at
      100 microM for 60 min, the intensities of eight spots increased and those of
      eight spots decreased on 2D gels, as compared with control gels, after staining
      with silver. These changes were also observed after exposure of cells to
      hydroperoxides such as cumene hydroperoxide and tert-butyl hydroperoxide, but not
      after exposure to other reagents that induce oxidative stress such as S
      alkylating compounds, nitric oxide, and salts of heavy metals. Therefore, these
      proteins were designated hydroperoxide responsive proteins (HPRPs).
      Microsequencing analysis revealed that these HPRPs corresponded to at least six
      pairs of proteins. Of these, four pairs of HPRPs were thioredoxin peroxidase I
      (TPx I), TPx II, TPx III, and the product of human ORF06, all of which belong to
      the peroxiredoxin (Prx) family and all of which are involved in the elimination
      of hydroperoxides. The other two pairs corresponded to heat shock protein 27
      (HSP27) and glyceraldehyde-3-phosphate dehydrogenase (G3PDH), respectively. The
      variants that appeared in response to hydroperoxides had molecular masses similar
      to the respective native forms, but their pI values were lower by 0.2-0.3 pH
      units than those of the corresponding native proteins. These variants were
      detected on 2D gels after cells had been exposed to hydroperoxides in the
      presence of an inhibitor of protein synthesis. All variants were generated within
      30 min of exposure to 100 microM H2O2. The variants of TPx I and TPx II appeared
      within 2 min of the addition of H2O2 to the culture medium. The HPRPs returned to
      their respective native forms after the removal of stress. Our results indicated
      that at least six proteins were structurally modified in response to
      hydroperoxides. Analysis by 2D-PAGE of 32P-labeled proteins revealed that the
      variant of HSP27 was its phosphorylated form while the other HPRPs were not
      modified by phosphorylation. Taken together, the results suggest that 2D-PAGE can
      reveal initial responses to hydroperoxide stress at the level of protein
      modification. Moreover, it is possible that the variants of four types of Prx
      might reflect intermediate states in the process of hydroperoxide elimination.

PMID- 11295361
TI  - Red wine polyphenols, in the absence of alcohol, reduce lipid peroxidative stress
      in smoking subjects.
AB  - Phenolic compounds in red wine can exert antioxidant effects on in vitro
      lipoprotein oxidation. This has led to speculation that red wine consumption
      mediates unique anti-atherosclerotic effects compared to other alcoholic
      beverages. However, studies assessing the effects of red wine consumption on
      lipoprotein oxidation ex vivo have not been conclusive. The recent identification
      of the F2-isoprostanes as oxidative products of arachidonic acid has provided a
      reliable measure of in vivo lipid peroxidation. This randomized trial
      investigated changes in plasma and urinary F2-isoprostane concentrations
      following red wine, white wine, or dealcoholized red wine consumption in humans.
      Eighteen male smokers consumed, in random order, red wine, white wine, or
      dealcoholized red wine, for two weeks with one week washout between beverages.
      Plasma and urinary F2-isoprostane concentrations were measured before and after
      each beverage. Serum gamma-glutamyl transpeptidase (gamma-GT) and urinary 4-O 
      methylgallic acid were measured as markers of alcohol consumption and phenolic
      acid absorption, respectively. Plasma F2-isoprostanes (p < .05) decreased
      significantly with dealcoholized red wine but not with the alcohol-containing
      beverages. Urinary excretion of F2-isoprostanes showed a similar trend. gamma-GT
      decreased significantly with dealcoholized red wine and increased with both
      alcohol-containing beverages (p < .01). Urinary excretion of 4-O-methylgallic
      acid increased significantly (p < .001) in the 24 h urine samples following red
      wine or dealcoholized red wine ingestion, but not with white wine. Serum urate
      increased and beta-carotene decreased with both alcoholic beverages relative to
      dealcoholized red wine. There was no change in the antioxidants alpha- and gamma
      tocopherol or vitamin C with any of the beverages. The results suggest that
      polyphenols in dealcoholized red wine can reduce in vivo lipid peroxidation as
      measured by F2-isoprostanes in smoking subjects. However, no reduction in lipid
      peroxidation was observed following red or white wine consumption, suggesting
      that any protective effects of wine drinking on cardiovascular disease are
      unlikely to be related to inhibition of lipid oxidation.

PMID- 11295362
TI  - Neuroprotective effect of hexasulfobutylated C60 on rats subjected to focal
      cerebral ischemia.
AB  - The effects of hexasulfobutylated C60 (FC4S), a free radical remover, on the
      total volume infarct size elicited by the damaging effects of focal cerebral
      ischemia were studied on Long-Evans rats in vivo. FC4S was administered
      intravenously either 15 min before middle cerebral artery (MCA) occlusion
      (pretreatment groups) or it was injected when the common carotid arteries clips
      were removed (treatment groups). FC4S did not alter the pH, blood gases, heart
      rate, or mean arterial blood pressure in either pretreatment or treatment groups
      of the rats. However, after administration of FC4S at dosages of 10 and 100
      microg/kg, the total volume of infarction was significantly reduced in both
      pretreatment and treatment groups. In addition, after FC4S administration, the
      nitric oxide (NO) content in plasma was increased and the lactate dehydrogenase
      (LDH) levels was decreased. It is concluded that FC4S may be used as a
      neuroprotective agent on focal cerebral ischemia. The beneficial effects may be
      partly related to its antioxidant property and to the upregulation of NO
      production of the compound.

PMID- 11295363
TI  - Detection of drug-induced, superoxide-mediated cell damage and its prevention by
      antioxidants.
AB  - The mode of the cytotoxic activity of three benzo(c)fluorene derivatives was
      characterized. The observed morphological changes of lysosomes or variations of
      mitochondrial activity are assumed to be the consequence of cell protection
      against oxidative damage and/or the part of the damage process. To establish the
      relationship between the quantity of superoxide (O2*-) generated and the degree
      of damage resulting from O2*-, a simple system based on measurement of 3-(4
      iodophenyl)-2-(4-nitrophenyl)-5-phenyltetrazolium chloride (INT) reductase
      activity in the presence of superoxide dismutase (SOD) was used. The
      functionality of the chosen battery of in vitro tests was proved using several
      known superoxide inducers: cyclosporin A (CsA) and benzo(a)pyrene (BP), as well
      as noninducers: citrinin (CT) and cycloheximide (CH). From the results followed
      that the cell growth tests are much better indices of toxicity than the other
      tests. The model system for the evaluation of the protective capacity of
      antioxidants against superoxide-induced cytotoxicity included simultaneous
      exposure of HeLa cells to cytotoxic drugs and to quercetin (Qe), an antioxidant
      of plant origin. The complete abolishment of the inhibition of cell proliferation
      and clonogenic survival was concluded to be due to the protective effect of the
      antioxidant. These observations correlated with the decrease of superoxide
      content as estimated by the INT-reductase assay in the presence of SOD using the
      same model system, as well as with the increase of intracellular SOD content and
      its activity.

PMID- 11295364
TI  - Erythrocyte, plasma, and serum antioxidant activities in untreated toxic
      multinodular goiter patients.
AB  - Erythrocyte, plasma, and serum antioxidant activities were studied in patients
      with newly diagnosed and untreated toxic multinodular hyperthyroid goiter and
      compared to healthy control subjects. Erythrocyte antioxidant enzyme activities,
      glutathione, malondialdehyde, and ceruloplasmin levels were significantly
      increased, whereas serum vitamin E, plasma vitamin C, and selenium levels were
      decreased in hyperthyroid patients compared to control subjects. The findings
      show that untreated toxic multinodular goiter causes profound alterations in
      components of the antioxidant system in erythrocytes indicative of increased
      oxidative stress. Taken together, these data suggest that hyperthyroid patients
      may benefit from dietary supplements of antioxidants.

PMID- 11295365
TI  - Role of membrane lipids in regulation of vulnerability to oxidative stress in
      PC12 cells: implication for aging.
AB  - Previously, we reported that PC12 cells showed increased vulnerability to
      oxidative stress (OS) induced by H2O2 (as assessed by decrements in calcium
      recovery, i.e., the ability of cells to buffer Ca(2+) after a depolarization
      event) when the membrane levels of cholesterol (CHL) and sphingomyelin (SPH) were
      modified to approximate those seen in the neuronal membranes of old animals. The
      present study was designed to examine whether the enrichment of the membranes
      with SPH-CHL and increased cellular vulnerability to OS are mediated by neutral
      SPH-specific phospholipase C (N-Sase) and the intracellular antioxidant GSH. The
      results showed a significant up-regulation of N-Sase activity by both low (5
      microM) and high (300 microM) doses of H2O2. However, under high doses of H2O2
      the up-regulation of N-Sase is accompanied by a significant increase in reactive
      oxygen species and by a decrease in intracellular GSH. The enrichment of
      membranes with SPH-CHL significantly potentiated the effects of high doses of
      H2O2, by further reducing the intracellular GSH and further up-regulating the N
      Sase activity. Furthermore, repleting intracellular GSH with 20 mM N
      acetylcysteine treatment was sufficient to attenuate the effect of a low dose of
      H2O2 on Ca(2+) recovery in SPH-CHL-treated cells. Thus, these results suggested
      that age-related alterations in the membrane SPH-CHL levels could be important
      determinants of the susceptibility of neuronal cells to OS.

PMID- 11295366
TI  - SIN-1-induced DNA damage in isolated human peripheral blood lymphocytes as
      assessed by single cell gel electrophoresis (comet assay).
AB  - Human lymphocytes were exposed to increasing concentrations of SIN-1, which
      generates superoxide and nitric oxide, and the formation of single-strand breaks
      (SSB) in individual cells was determined by the single-cell gel electrophoresis
      assay (comet assay). A dose- and time-dependent increase in SSB formation was
      observed rapidly after the addition of SIN-1 (0.1-15 mM). Exposure of the cells
      to SIN-1 (5 mM) in the presence of excess of superoxide dismutase (0.375 mM)
      increased the formation of SSB significantly, whereas 1000 U/ml catalase
      significantly decreased the quantity of SSB. The simultaneous presence of both
      superoxide dismutase and catalase before the addition of SIN-1 brought the level
      of SSB to that of the untreated cells. Moreover, pretreatment of the cells with
      the intracellular Ca(2+)-chelator BAPTA/AM inhibited SIN-1-induced DNA damage,
      indicating the involvement of intracellular Ca(2+) changes in this process. On
      the other hand, pretreatment of the same cells with ascorbate or dehydroascorbate
      did not offer any significant protection in this system. The data suggest that
      H2O2-induced changes in Ca(2+) homeostasis are the predominant pathway for the
      induction of SSB in human lymphocytes exposed to oxidants.

PMID- 11295367
TI  - Effects of reactive oxygen species on proliferation of Chinese hamster lung
      fibroblast (V79) cells.
AB  - Reactive oxygen species (ROS) have emerged as important signaling molecules in
      the regulation of various cellular processes. In our study, we investigated the
      effect of a wide range of ROS on Chinese hamster lung fibroblast (V79) cell
      proliferation. Treatment with H2O2 (100 microM), superoxide anion (generated by 1
      mM xanthine and 1 mU/ml xanthine oxidase), menadione, and phenazine methosulfate
      increased the cell proliferation by approximately 50%. Moreover, a similar result
      was observed after partial inhibition of superoxide dismutase (SOD) and
      glutathione peroxidase. This upregulation of cell proliferation was suppressed by
      pretreatment with hydroxyl radical scavengers and iron chelating agents. In
      addition to ROS, treatment with exogenous catalase and SOD mimic (MnTMPyP)
      suppressed the normal cell proliferation. Short-term exposure of the cells to 100
      microM H2O2 was sufficient to induce proliferation, which indicated that
      activation of the signaling pathway is important as an early event. Accordingly,
      we assessed the ability of H2O2 to activate mitogen-activated protein kinases
      (MAPK). Jun-N-terminal kinase (JNK) and p38 MAPK were both rapidly and
      transiently activated by 100 microM H2O2, with maximal activation 30 min after
      treatment. However, the activity of extracellular signal-regulated kinase (ERK)
      was not changed. Pretreatment with SB203580 and SB202190, specific inhibitors of
      p38 MAPK, reduced the cell proliferation induced by H2O2. The activation of both
      JNK and p38 MAPK was also suppressed by pretreatment with hydroxyl radical
      scavenger and iron chelating agents. Our results suggest that the trace metal
      driven Fenton reaction is a central mechanism that underlies cell proliferation
      and MAPK activation.

PMID- 11295368
TI  - Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic
      cells.
AB  - 4-Hydroxynonenal (HNE), a reactive and cytotoxic end-product of lipid
      peroxidation, has been suggested to be a key mediator of oxidative stress-induced
      cell death and in various cell types has been shown to induce apoptosis. We have
      demonstrated that HNE, at micromolar concentrations, induces dose- and time
      dependent apoptosis in a leukemic cell line (CEM-C7). Interestingly, much higher
      concentrations of HNE (> 15-fold) were required to induce apoptosis in leukocytes
      obtained from normal individuals. We also demonstrate that HNE causes a decrease
      in clonogenicity of CEM-C7 cells. Furthermore, our data characterize the caspase
      cascade involved in HNE-induced apoptosis in CEM-C7 cells. Using specific
      fluorogenic substrates and irreversible peptide inhibitors, we demonstrate that
      caspase 2, caspase 3, and caspase 8 are involved in HNE-induced apoptosis, and
      that caspase 2 is the first initiator caspase that activates the executioner
      caspase 3, either directly or via activation of caspase 8. Our studies also
      suggest the involvement of another executioner caspase, which appears to be
      similar to caspase 8 but not caspases 2 and 3, in its specificity. The
      demonstration of decreased clonogenicity by HNE in the leukemic cells, and their
      higher susceptibility to HNE-induced apoptosis as compared to the normal cells,
      suggests that such compounds may have potential for leukemia chemotherapy.

PMID- 11295369
TI  - An event-related functional magnetic resonance imaging study of an auditory
      oddball task in schizophrenia.
AB  - Schizophrenia is a diffuse brain disease that affects many facets of cognitive
      function. One of the most replicated findings in the neurobiology of
      schizophrenia is that the event-related potentials to auditory oddball stimuli
      are abnormal, effects believed to be related to abnormalities in attentional and
      memory processes. Although event-related potentials provide excellent resolution
      regarding the time course of information processing, such studies are poor at
      characterizing the spatial location of these abnormalities. To address this
      issue, we used event-related functional magnetic resonance imaging techniques to
      elucidate the neural areas underlying target detection in schizophrenia.
      Consistent with recent event-related functional magnetic resonance imaging
      results, target processing by control participants was associated with bilateral
      activation in the anterior superior temporal gyri, inferior and superior parietal
      lobules, and activation in anterior and posterior cingulate, thalamus, and right
      lateral frontal cortex. For the schizophrenic patients, selective deficits were
      observed in both the extent and strength of activation associated with target
      processing in the right lateral frontal cortex, thalamus, bilateral anterior
      superior temporal gyrus, anterior and posterior cingulate, and right inferior and
      superior parietal lobules. These findings are consistent with the evidence for
      abnormal processing of oddball stimuli suggested by event-related potential
      studies in schizophrenic patients, but provide much more detailed evidence
      regarding the anatomical sites implicated. These data are consistent with the
      hypothesis that schizophrenia is characterized by a widespread pathological
      process affecting many cerebral areas, including association cortex and thalamus.

PMID- 11295370
TI  - Prefrontal cortical sulcal widening associated with poor treatment response to
      clozapine.
AB  - Increased sulcal widening in the prefrontal cortex of patients with schizophrenia
      may be associated with a poor treatment response to clozapine. To further
      evaluate this, we examined data from patients treated with clozapine in our
      center. Patients with the greatest degree of improvement (n=26) and those with no
      improvement (n=10) were compared. Computerized tomography (CT) scans were rated
      blindly on a visual scale of prefrontal sulcal widening. Patients with the
      greatest degree of functional improvement had significantly less prefrontal
      sulcal widening than those whose symptoms remained unchanged. There was no
      relationship between clozapine response and general sulcal widening. These data
      support the link between the superior therapeutic efficacy of clozapine and the
      integrity of the prefrontal cortex.

PMID- 11295371
TI  - Sex differences in the absence of massa intermedia in patients with schizophrenia
      versus healthy controls.
AB  - OBJECTIVE: To evaluate sexual dimorphism and incidence of absent massa intermedia
      (MI), a midline thalamic structure, in patients with schizophrenia and healthy
      controls. METHODS: Thin slice magnetic resonance images of the brain were
      obtained. The presence of MI was determined by viewing sagittal, coronal, and
      axial planes. RESULTS: In healthy controls, females had a significantly lower
      incidence of absent MI (13.56%) compared with males (32.08%). In patients with
      schizophrenia, there was a sex by diagnosis interaction. Female patients had
      significantly higher incidence of absent MI (32.76%) compared with their healthy
      controls (13.56%), whereas the male patients showed no difference in incidence of
      absent MI compared with their controls. CONCLUSION: The MI, a sexually dimorphic
      midline structure, is more commonly absent in female patients with schizophrenia.
      These results support the growing literature reporting structural aberration of
      the thalamus, as well as other midline structures in the brains of patients with
      schizophrenia.

PMID- 11295372
TI  - Temporal lobe volume determined by magnetic resonance imaging in schizotypal
      personality disorder and schizophrenia.
AB  - The volumes of the whole temporal lobe, the superior temporal gyrus and the
      corpus callosum were measured on magnetic resonance images from 13 patients with
      schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31
      age- and sex-matched controls. Temporal lobe structures were traced on
      consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal
      lobes than normal volunteers, a difference that was more marked for the area
      outside the superior temporal gyrus than for the STG. Correcting for brain volume
      diminished differences between normal subjects and schizophrenia patients, but
      the differences between normal subjects and SPD patients remained. Normal
      volunteers and SPD patients showed significant correlations between the sagittal
      section area of the posterior portion of the corpus callosum, which carries
      temporal interhemispheric connections, and the white matter volume of the
      temporal lobe. While the sample size is modest, taken together, these results
      suggest that the psychopathological symptoms of SPD may be related to temporal
      gray matter loss with relatively intact white matter connectivity, while the
      cognitive and psychotic symptoms of schizophrenia may be related to temporal gray
      loss combined with disruption of normal patterns of white matter development.

PMID- 11295373
TI  - Prevalence of cavum septum pellucidum in schizophrenia studied with MRI.
AB  - OBJECTIVE: To study the prevalence of cavum septum pellucidum (CSP), a midline
      developmental anomaly, in patients with schizophrenia. METHODS: Three-millimeter
      coronal T1 weighted MRI images of 43 normal controls and 73 patients with
      schizophrenia were examined. The images were resampled into 1-mm slices and CSP
      was measured by the number of slices in which it appeared. RESULTS: Patients had
      significantly higher incidence of CSP (Fisher's exact test 0.042; one-sided).
      Eighteen (41.9%) of the controls and 44 (60.3%) of patients had a CSP, and one of
      46 controls and three of 73 patients had a large CSP of six slices or more. There
      was no relationship between the presence or size of CSP and regional brain
      volumes or volumes of hippocampus-amygdala complex, caudate, superior temporal
      gyrus or ventricular CSF. CONCLUSION: Higher incidence of CSP may reflect a
      neurodevelopmental disturbance in schizophrenia.

PMID- 11295374
TI  - Hypofrontality -- a risk-marker related to schizophrenia?
AB  - In order to better understand whether cortical hypoactivation and hypofrontality
      is a possible risk marker for schizophrenia, we investigated resting EEG activity
      in 39 unmedicated schizophrenics and 21 persons with schizotypal personality.
      Compared to a normal control group, we found an increased, frontally pronounced
      delta activity in schizophrenic patients, a result that is in accordance with
      other studies. Subjects with schizotypal personality, who are believed to have an
      increased risk for schizophrenia, did not show an increase of delta activity.
      From this result, we concluded that cortical hypoactivation and hypofrontality --
      defined as an increase of frontally pronounced delta activity during resting EEG 
      - cannot be interpreted as a risk factor for schizophrenia. However, since it is
      controversial whether subjects with schizotypal personality are at increased risk
      for schizophrenia, further studies in unaffected family members of schizophrenic
      patients are needed.

PMID- 11295375
TI  - Outcome in children with fetal mild ventriculomegaly: a case series.
AB  - Mild enlargement of the lateral ventricles is associated with schizophrenia and
      other neurodevelopmental disorders. While it has been hypothesized that ventricle
      abnormalities associated with neurodevelopmental disorders arise during fetal
      brain development, there is little direct evidence to support this hypothesis.
      Using ultrasound, it is possible to image the fetal ventricles in utero. Fetal
      mild ventriculomegaly (MVM) has been associated with developmental delays in
      early childhood, though longer-term neurodevelopmental outcome has not been
      studied. Follow-up of five children (aged 4--9 years) with mild enlargement of
      the lateral ventricles on prenatal ultrasound and two unaffected co-twins is
      reported: one child had attention deficit hyperactivity disorder (ADHD), one had
      autism, and two had evidence of learning disorders. These cases suggest that the
      mild enlargement of the lateral ventricles associated with these
      neurodevelopmental disorders arises during fetal brain development and can be
      detected with prenatal ultrasound. In addition, the presence of mildly enlarged,
      asymmetric ventricles in two children on prenatal ultrasound and on follow-up MRI
      at age 6 years indicates that ventricle structure present in utero can persist
      well into childhood brain development. The study of fetal ventricle development
      with ultrasound may provide important insights into neurodevelopmental disorders
      and allow the identification of children at high risk.

PMID- 11295376
TI  - Schizophrenia and season of birth in a tropical region: relationship to rainfall.
AB  - Winter birth has been shown to increase the risk of schizophrenia in adult life.
      It has been hypothesized that this effect is due to seasonal variation in
      infectious diseases, including influenza, as exposure to influenza during mid
      gestation also increases the risk of schizophrenia. However, in many areas there
      is little variation in temperature during the year, although rainfall may vary
      greatly. We tested the hypothesis that, in a tropical region with wet and dry
      seasons, schizophrenia births would be related to rainfall. The data came from
      the city of Mossoro in north-eastern Brazil. In this area there is no meaningful
      variation in temperature, but there is a rainy season with little precipitation
      during the rest of the year. In this region, the prevalence of influenza
      parallels that of rainfall. There was a significant relationship between rainfall
      and the number of schizophrenia births three months later. In contrast, there was
      no significant relationship between rainfall and general population births three
      months later. The relationship of birth to rainfall, rather than winter birth,
      may be associated with risk of schizophrenia in tropical regions; exposure to
      influenza during gestation may be the basis for such a relationship.

PMID- 11295377
TI  - Facial affect and affective prosody recognition in first-episode schizophrenia.
AB  - Individuals with schizophrenia experience problems in the perception of emotional
      material; however, the specificity, extent, and nature of the deficits are
      unclear. Facial affect and affective prosody recognition were examined in
      representative samples of individuals with first-episode psychosis, assessed as
      outpatients during the early recovery phase of illness, and non-patients.
      Perception tasks were selected to allow examination of emotion category results
      across face and voice modalities. Facial tasks were computerised modifications of
      the Feinberg et al. procedure (Feinberg, T.E., Rifkin, A., Schaffer, C., Walker,
      E., 1986. Arch. Gen. Psychiatry 43, 276--279). Prosody tasks were developed using
      four professional actors, and item selections were based on responses of
      undergraduates. Participant groups did not differ in their understanding of the
      words used to describe emotions. Findings supported small but consistent deficits
      in recognition of fear and sadness across both communication channels for the
      combined schizophrenia (n=29) and other psychotic disorders (n=28) groups as
      compared to the affective psychoses (n=23) and non-patients (n=24). A diagnostic
      effect was evident that was independent of the contribution of intelligence. The
      detection of emotion recognition impairments in first-episode schizophrenia
      suggests a trait deficit. The pattern of results is consistent with amygdala
      dysfunction in schizophrenia and related psychoses.

PMID- 11295378
TI  - Generalization of training effects in schizophrenia.
AB  - The primary goal of this study was to investigate transfer of training
      (generalization) in patients with schizophrenia. We randomly assigned 33
      schizophrenia subjects to one of three conditions: training on the Wisconsin Card
      Sort Test (WCST-T), training on the Halstead Category Test (CAT-T), or no
      training (No-T). The WCST and CAT were administered to all subjects at baseline.
      Subjects in the WCST-T and CAT-T groups then received training on the respective
      test, while the No-T group received additional untrained trials. All participants
      were subsequently retested on the WCST and CAT, and completed a brief
      neuropsychological battery. As hypothesized, the WCST-T and CAT-T groups
      exhibited large improvements on the trained test and moderate improvement on the
      untrained test, while the No-T group failed to show improvement on either test.
      These results suggest that the training paradigm did produce generalization, and
      that the changes were not due to practice effects. The extent of generalization
      across both training groups was strongly associated with neuropsychological test
      performance (Spearman's rho=0.56, P<0.05). The implications of these findings for
      rehabilitation programs were discussed, and recommendations were made for future
      research.

PMID- 11295379
TI  - Sustained and selective attention as measures of genetic liability to
      schizophrenia.
AB  - We tested for a relationship between attention and genetic liability to
      schizophrenia. Samples of probands with DSM-IV schizophrenia (n=20), their well
      first-degree relatives (n=40) and healthy controls (n=82) were tested using
      measures of sustained attention (degraded-stimulus continuous performance test:
      DS-CPT) and selective attention (spatial negative priming task). Assuming a
      liability-threshold model, we predicted that probands would display greater
      attentional decrements than controls and that the relatives would show
      intermediate levels of decrement. We did not observe the predicted pattern of
      effect using either measure, although the probands showed a trend towards less
      negative priming. However, our results may have been affected by self-selection
      bias in probands and relatives and clinical heterogeneity among probands, which
      could have reduced our power to detect effects.

PMID- 11295380
TI  - Impaired associative learning in chronic schizophrenics and their first-degree
      relatives: a study of latent inhibition and the Kamin blocking effect.
AB  - The performance of chronic schizophrenic probands (n=21), their first-degree
      schizotypal (22) and non-schizotypal (19) relatives, and normal controls (24),
      was measured in two associative learning paradigms, latent inhibition and the
      Kamin blocking effect. These paradigms assess the effects on learning of initial
      exposure to other learning contingencies. The normal subjects showed latent
      inhibition (retarded learning of an association between a burst of white noise
      and a visually displayed counter increment, if the subject had first been pre
      exposed to the white noise without any other consequence) and Kamin blocking
      (retarded learning of an association between two visual stimuli, if the
      conditioned stimulus was presented simultaneously with a second, already
      conditioned stimulus). The schizophrenic probands and both the schizotypal and
      non-schizotypal relatives were severely impaired in basic associative learning,
      performing much worse than the normal subjects in the control conditions (i.e.
      those lacking stimulus pre-exposure of any kind) of both the latent inhibition
      and the Kamin paradigms and also showed a loss of the normal latent inhibition
      and Kamin blocking effects. The performance of the three clinically defined
      groups was statistically indistinguishable. These findings contrast with previous
      reports of the performance of normal subjects classified as schizotypal by
      questionnaire, who are not impaired in basic associative learning, and are
      particularly fast to learn after stimulus pre-exposure. The results question the
      assumption that high schizotypy, as assessed by questionnaire, is like schizotypy
      in schizophrenic kin. The severe impairment in basic associative learning in
      schizophrenic patients and their kin warrants further investigation.

PMID- 11295381
TI  - Negative priming in schizophrenia: effects of masking and prime presentation
      time.
AB  - Beech et al. [Br. J. Clin. Psychol. 28 (1989) 109--116] previously reported
      attenuated negative priming in schizophrenic patients that was interpreted as a
      sign of dysfunctional cognitive inhibition. However, subsequent research has
      provided mixed results. In the present study, it was investigated whether reduced
      negative priming in schizophrenics may be an experimental artifact. Based on
      evidence from backward masking studies in schizophrenia, it was hypothesized that
      brief prime presentation times and pattern masking as used by Beech et al. and
      others may have impaired the visual perception of the prime display in
      schizophrenics. 20 schizophrenic patients and 20 matched healthy controls
      participated in the study. Subjects completed four negative priming experiments
      varying in prime presentation time (100 or 250 ms) and masking (a mask or a blank
      screen followed prime presentation). In line with prediction, reduced negative
      priming in schizophrenics only occurred for trials with 100 ms prime presentation
      time followed by a mask. Neither psychopathology nor any sociodemographic
      variable correlated substantially with negative priming. Results strongly suggest
      that reduced negative priming in schizophrenics may not be due to reduced
      cognitive inhibition but mirrors perceptual deficits.

PMID- 11295382
TI  - Enhanced semantic priming in thought-disordered schizophrenic patients using a
      word pronunciation task.
AB  - Previous research on semantic priming in schizophrenia has produced contradictory
      findings. For the present study, it was intended to resolve some of the
      ambiguities in the literature. Using a semantic priming task with word
      pronunciation, evidence is provided that thought-disordered schizophrenic (TD)
      patients exhibit significantly increased semantic priming as compared to healthy
      and psychiatric controls. Results suggest that enhanced semantic priming is not
      confined to tasks that require lexical decision. Moreover, results indicate that
      TD schizophrenic patients suffer from a decay of hierarchical thinking, i.e. TD
      schizophrenics reveal a tendency to process the less meaningful rather than the
      dominant aspects of external information. Priming effects for the inferior
      meaning of homograph words (for example, 'dance' is an inferior, and 'game' is a
      superior associate of the word 'ball') were significantly greater compared to
      healthy controls and non-TD schizophrenics. Results were not moderated by
      sociodemographic background variables, psychomotor slowing and psychopathological
      symptoms other than thought disorder.

PMID- 11295383
TI  - Comparison of the continuous performance test with and without working memory
      demands in healthy controls and patients with schizophrenia.
AB  - The Penn Continuous Performance Test (PCPT), a measure of sustained visual
      attention developed for use in functional neuroimaging studies, was compared with
      a standard CPT developed by Gordon Diagnostic Systems (GDS; Vigilance subtest).
      The PCPT and the GDS CPT were administered with a standard neuropsychological
      battery to 68 healthy adults to assess reliability and construct validity. The
      test had adequate internal consistency, and convergent validity was established
      through significant correlations between measures of efficiency on the PCPT and
      the GDS CPT. With the exception of a significant correlation between efficiency
      measures on the GDS CPT and a measure of auditory sustained attention, neither
      version of the CPT correlated significantly with other measures in the battery.
      Factor analysis showed that the PCPT loaded with the GDS CPT. In 39 patients with
      schizophrenia and 39 matched, healthy controls, equivalent impairment was evident
      on the two CPT tasks. Neither version correlated significantly with symptom
      measurements. These results support previous conclusions that sustained visual
      attention in schizophrenia is a core information processing deficit, not directly
      related to symptomatology.

PMID- 11295384
TI  - Psychomotor slowing and planning deficits in schizophrenia.
AB  - The relative contribution of cognitive and motor processing to psychomotor
      slowing in schizophrenia was investigated using three tasks: a simple line
      copying task and a more complex figure-copying task, both following a reaction
      paradigm, and a standard psychomotor test, the Digit Symbol Test (DST). Various
      movement variables of the task performances were derived from recordings made
      with the aid of a digitizing tablet. The patients with schizophrenia appeared to
      be about one-third slower in their total performance time on all three tasks when
      compared with healthy controls, which suggests a general psychomotor slowing in
      this group. When itemized over the various movement variables, this slowing was
      found in both initiation time and movement time in the copying tasks and in the
      DST in the time to match the symbol and the digit, but not in writing the digit.
      Furthermore, in the figure-copying task it was found that increased figure
      complexity or decreased familiarity prolonged the initiation time. These latency
      increases were not significantly larger for the schizophrenia group as a whole,
      but only for a subgroup of patients with higher scores on negative symptoms.
      Regarding reinspection time, the effects of familiarity were larger in the
      schizophrenia group as a whole. These group findings suggest that patients tend
      to plan their actions less in advance, which, in the case of the more complex or
      unfamiliar task conditions, is a less sophisticated planning strategy. Given the
      longer latencies in patients with more severe negative symptoms, it seems that
      these patients have problems with turning a plan into action. The present study
      provides evidence of psychomotor slowing and planning deficits in schizophrenia.

PMID- 11295385
TI  - Cognitive therapy for psychosis in schizophrenia: an effect size analysis.
AB  - We conducted a meta-analysis using all available controlled treatment outcome
      studies of cognitive therapy (CT) for psychotic symptoms in schizophrenia. Effect
      sizes were calculated for seven studies involving 340 subjects. The mean effect
      size for reduction of psychotic symptoms was 0.65. The findings suggest that
      cognitive therapy is an effective treatment for patients with schizophrenia who
      have persistent psychotic symptoms. Follow-up analyses in four studies indicated
      that patients receiving CT continued to make gains over time (ES=0.93). Further
      research is needed to determine the replicability of standardized cognitive
      interventions, to evaluate the clinical significance of cognitive therapy for
      schizophrenia, and to determine which patients are most likely to benefit from
      this intervention.

PMID- 11295386
TI  - Shyness, sociability, and social dysfunction in schizophrenia.
AB  - Recent bio-developmental models of shyness traits (Schmidt, L.A., Fox, N.A.,
      1998. The development and outcomes of childhood shyness. Annals of Child
      Development 13, 1--20; Schmidt, L.A. Fox, N.A., 1999. Conceptual, biological, and
      behavioural distinctions among different types of shy children. In: Schmidt,
      L.A., Schulkin, J. (Eds.), Extreme Fear, Shyness, and Social Phobia: Origins,
      Biological Mechanisms, and Clinical Outcomes. Oxford University Press, New York,
      pp. 47--66) have proposed that childhood shyness and early sociability troubles
      may be a precursor to pervasive social dysfunction in adulthood. An important
      question in testing the vulnerability model is to determine the severity of
      shyness among adults who have a serious social dysfunction, such as individuals
      diagnosed with schizophrenia. The Cheek and Buss Shyness and Sociability Scales
      (Cheek, J.M., Buss, A.H., 1981. Shyness and sociability. Journal of Personality
      and Social Psychology 41, 330--339) and the Reznick Retrospective Self-report of
      Inhibition (Reznick, J.S., Hegeman, I.N., Kaufman, E.R., Woods, S.W., Jacobs, M.,
      1992. Retrospective and concurrent self-report of behavioural inhibition and
      their relation to adult mental health. Development and Psychopathology 4, 301-
      321) were administered to 23 schizophrenia outpatients and 23 control subjects
      matched for age and sex. The results indicated that individuals with
      schizophrenia showed significantly more shyness (P<0.004), lower sociability
      (P<0.02) and more recollections of childhood social troubles (P<0.007) compared
      with the control group. Within the schizophrenia group, both shyness traits
      (P<0.04) and limited sociability (P<0.01) were clearly associated with
      interpersonal dysfunction, while significant correlations were also found between
      troubled sociability and negative symptoms (P<0.05). The findings of shyness
      traits, impaired sociability and more recollections of childhood social
      difficulties among stable outpatients diagnosed with schizophrenia are consistent
      with predictions based on a bio-developmental shyness vulnerability model.

PMID- 11295387
TI  - Social skills performance assessment among older patients with schizophrenia.
AB  - OBJECTIVE: Social functioning is an important outcome dimension in schizophrenia.
      Measures of social skills frequently rely on self-report, and most measures which
      directly assess social functioning are time consuming. Here we describe a brief
      performance-based measure, the Social Skills Performance Assessment (SSPA),
      modified from an instrument published by Bellack et al. (Bellack, A., Morrison,
      R., Wixted, J., Mueser, K., 1990. An analysis of social competence in
      schizophrenia. Br. J. Psychiatry 156, 809--818). METHOD: 83 middle-aged and
      elderly patients with schizophrenia or schizoaffective disorder, and 52 normal
      comparison subjects (NCs) were rated on two standardized role plays, one
      requiring introduction to a stranger and another requiring assertive behavior
      with their landlord. Ratings in eight areas ranging from 'social appropriateness'
      to 'grooming' were made. RESULTS: SSPA required about 12 min to complete both
      role play and ratings, and had excellent interrater reliability, and good test
      retest reliability. Patients demonstrated significantly greater disability in all
      areas of social functioning compared with NCs. Social performance was related to
      severity of negative symptoms and cognitive deficits, but not that of positive or
      depressive symptoms. SSPA scores were significantly correlated with health
      related quality of well-being and observed performance on activities of daily
      living, but not to a self-reported measure of social functioning. CONCLUSION: The
      SSPA is a reliable and useful instrument. Direct assessment of social skills may
      provide a more accurate picture of functioning than self-report measures among
      patients who frequently lack insight into their own behavior.

PMID- 11295388
TI  - AMPA receptor binding in the dorsolateral prefrontal cortex of schizophrenics and
      controls.

PMID- 11295389
TI  - Neurocognitive and social functioning in schizophrenia and other diagnoses.

PMID- 11295390
TI  - Visuoperceptual test performance in schizophrenia: evaluating the component
      processes of visual memory.

PMID- 11295391
TI  - Ownership pattern and management practices of small ruminants in The Gambia -
      implications for a breeding programme.
AB  - In the framework of a genetic improvement scheme a countrywide survey of small
      ruminant owners was conducted in The Gambia to obtain information about the
      ownership pattern, reasons for keeping and especially about breeding and
      management practices including housing and feeding. The main results were the
      following: women play a major role in small ruminant production, representing 52%
      of the owners of sheep, 67% of the owners of goats and 43% of the owners of both
      sheep and goats. The average number of animals owned is quite low (about six head
      of sheep and goats each, out of which about three are breeding females). Most of
      the breeding males are born in their respective flock and there are fewer
      breeding bucks than breeding rams. However, there are sufficient numbers of
      breeding males around. Animals are mainly left free to roam around during the dry
      season, and are either tethered or herded in the rainy season. During night
      animals are housed or tied under a shelter. Supplementary feeding is not common
      and vaccination against Pest des Petit Ruminants (PPR) and Pasteurellosis is only
      partly carried out. Implications for the establishment and structure of a
      multiplication tier within a three tier breeding scheme, nucleus-->multipliers-
      >farmers are discussed.

PMID- 11295392
TI  - Trypanosomosis in small ruminants maintained by low riverine tsetse population in
      central Nigeria.
AB  - The prevalence of trypanosomosis was investigated over a 12-month period, among
      small ruminants grazing in known sleeping sickness endemic area of central
      Nigeria and under light riverine tsetse challenge. Analysis of the data from 304
      Yankassa sheep and 239 West African DwarfxRed Sokoto goats indicated high mean
      prevalence (27.62%, confidence limits Cl: 0.232, 0.312). Interspecies difference
      between sheep (38.16%; 0.382, Cl: 0.332, 0.432) and goats (14.23%; 0.142, Cl:
      0.102, 0.182) was highly significant (P<0.001). Infections were also
      significantly higher (P<0.05) with agro-pastoral (extensive) management, during
      the dry season and in adults compared to intensively managed animals, the wet
      season and young animals, respectively. Trypanosoma vivax was the predominant
      parasite encountered and accounted for over 49% of the infections. T. congolense
      and mixed populations were diagnosed at approximately 15% each while T. brucei
      were absent in caprines. The implications of these findings in the epidemiology
      of the diseases in both man and domestic animals is discussed.

PMID- 11295393
TI  - Comparison of the effects of atipamezole and tolazoline on analgesia,
      cardiopulmonary and rectal temperature changes induced by lumbosacral epidural
      injection of medetomidine in goats.
AB  - The present study was carried out in order to compare the reversing effects of
      alpha(2)-adrenergic receptor antagonists, atipamezole and tolazoline on
      analgesia, cardiopulmonary depression and rectal temperature changes induced by
      epidural administration of medetomidine in goats. Eight clinically healthy, small
      East African goats of both sexes weighing between 12 and 17kg (mean 14.4+/-1.8kg)
      were used in this study. The animals were randomly divided into two groups of
      four animals. The first group was given 20ug/kg medetomidine followed by
      intravenous (IV) administration of 80ug/kg atipamezole, 30min after the initial
      injection. The second group was given same treatment for medetomidine as group
      one but followed by IV administration of 2.2mg/kg tolazoline, 30min after the
      initial injection. In both treatment groups, medetomidine was administered
      epidurally through the lumbosacral interspace. Analgesia of the flank and
      perineum was evaluated at every 10min intervals up to 60min. The cardiopulmonary
      and rectal temperature values were monitored and recorded at every 5min interval
      up to 60min. In both groups, lumbosacral epidural injection of medetomidine
      induced generalised analgesia, variable cardiopulmonary depression effects and
      non-significant changes on rectal temperature. These changes developed as early
      as 5min and continued until alpha(2)/alpha(1) antagonists were administered.
      Intravenous administration of alpha-adrenergic receptor antagonists; atipamezole
      and tolazoline reversed analgesia, cardiopulmonary and rectal temperature changes
      induced by lumbosacral epidural injection of medetomidine in goats. However,
      atipamezole appeared to be superior (P<0.05) to tolazoline. From this study, it
      was concluded that IV administration of 80ug/kg atipamezole was better than
      2.2mg/kg tolazoline in reversing analgesia and cardiopulmonary depression effects
      induced by lumbosacral epidural injection of medetomidine in goats. This
      indicates the superiority of atipamezole to tolazoline as an antidote for
      medetomidine induced effects in goats.

PMID- 11295394
TI  - Digestibility, N balance and blood metabolite levels in Alpine goat wethers fed
      either water oak or shining sumac leaves.
AB  - Eight Alpine wethers (8-9 months of age, 27.5+/-1.10kg body weight (BW)) were
      randomly assigned to consume, free-choice, either shining sumac (Rhus copallina)
      or water oak (Quercus nigra) leaves as a sole diet. Leaves were collected and
      dried prior to feeding. A 14-day adaptation period was followed by a 4-day total
      fecal and urine collection. Chemical composition (%) of the fed water oak and
      shining sumac leaves revealed similar levels of OM (95.9 and 94.1) and N (1.54
      and 1.42) but higher concentrations of cell wall fractions, NDF (54.8 and 31.2)
      and ADF (34.5 and 26.4), in water oak than shining sumac. Body weight of wethers
      differed between treatments, although this was not reflected in DM intake.
      Average daily intake values were 616g DM, 589g OM and 9.3g N. NDF intake was
      significantly lower (P=0.002) in goats-fed shining sumac than in those that
      consumed water oak (192 versus 330g). Daily fecal output of all components was
      higher (P<0.05) in water oak than shining sumac-fed goats. Apparent
      digestibilities (%) of all components were significantly lower in water oak than
      shining sumac-fed animals (DM 41 versus 63, OM 42 versus 64, NDF 24 versus 37,
      and N 27 versus 38). Urinary N excretion, N balance and concentrations of
      protein, plasma urea nitrogen (PUN) and glucose in the blood were similar between
      diets, averaging 2.6g N per day, 0.45g per day, 85.5mg/ml, and 14.1mg/dl,
      respectively. The results of this trial suggest that shining sumac is utilized
      better by goats than water oak. The use of dried leaves in this experiment may
      have led to possible negative effects on nutrient characteristics that animals
      consuming fresh leaves may not experience.

PMID- 11295395
TI  - Effects of prenatal source and level of dietary selenium on passive immunity and
      thermometabolism of newborn lambs.
AB  - The objective of this study was to determine the effects of the amount and
      chemical form of Se fed to pregnant ewes on concentrations of thyroid hormones,
      Se in tissues, immunoglobulins (Ig) in serum, and measures of thermometabolism in
      ewes and their newborn lambs. Pregnant ewes (n=21) were randomly assigned to
      receive a diet deficient of Se (<0.02ppm) or supplemented to provide 0.3ppm Se
      from either sodium selenite or selenized yeast (SeY). Pregnant ewes which were
      fed additional Se had increased (P<0.05) concentrations of Se in whole blood and
      serum, greater activity of glutathione peroxidase (GSHpx), and higher
      concentrations of tri-iodothyronine (T(3)) and thyroxine (T(4)). At 12h of age,
      lambs of ewes given Se had higher (P<0.05) concentrations of Se in blood and
      liver, greater activities of GSHpx, and tended (P<0.1) to have higher T(3)
      levels. When the two Se supplements were compared, lambs of ewes which were fed
      with SeY had higher (P<0.001) concentrations of Se and activities of GSHpx
      (P<0.05) in blood than lambs of ewes fed with selenite. Concentrations of Se in
      colostrum were increased (P<0.05) with Se supplementation and the ewes fed with
      SeY tended (P<0.1) to have higher Se in colostrum than ewes fed with selenite.
      Although IgG in serum and colostrum of ewes was not affected by supplemental Se,
      IgM in serum of ewes was increased (P<0.05). Lambs of ewes which were given Se
      had increased (P<0.05) absorption of IgG, but not IgM. No treatment effects on
      measures of thermometabolism were detected. In conclusion, Se supplementation of
      pregnant ewes affected measures of thyroxine metabolism and immunity. Compared to
      selenite, Se from SeY was more readily transferred to the fetus and colostrum.

PMID- 11295396
TI  - Nutritive value and palatability of guajillo (Acacia berlandieri) as a component
      of goat diets.
AB  - Guajillo (Acacia berlandieri Benth.) is a low-growing, multi-stemmed shrub widely
      distributed in southern Texas and northern Mexico. Proximate analysis indicates
      the leaves have high concentrations of nitrogen and energy suggesting that it is
      a potentially valuable forage resource, yet excessive consumption is believed to
      cause a hind-limb ataxia. The nutritive value of, and their preference for,
      guajillo leaves was determined in two trials using male Angora goats (8 months
      old, 23.7+/-1.09kg initial weight). In a metabolism trial, air-dried guajillo
      leaves and alfalfa hay were chopped and mixed to prepare four diets containing 0,
      25, 50 and 75% of guajillo leaves, which were fed in a 4x4 Latin Square design.
      Animals were retained in metabolism crates for a 10 day adaptation period
      followed by a 7 day collection period. Diets were analyzed for DM, OM, N, NDF,
      ADF, ADF-N, cellulose, lignin, gross energy, phenolic amines, and bovine serum
      albumin precipitating capacity. Feed DM and OM intake, water consumption, fecal
      and urine output, nitrogen and energy balance, and urine glucuronic acid output
      was determined on the animals. Dietary concentration of guajillo had no effect
      (P>0.05) on intake (26.25+/-1.86g OM kg(-1) BW). Water intake and urine output
      decreased (P<0.05) with increasing guajillo in the diets, but water retention
      increased (P<0.05) with increasing guajillo. The digestibility of all the
      nutrients decreased (P<0.05) with increasing level of guajillo, with ADF
      digestibility reduced to zero in the 75% guajillo diet. Energy balance and
      nitrogen balance expressed as percent intake decreased (P<0.05) with increasing
      level of guajillo. Increasing ADF-N, together with reduced ADF digestibility,
      reduced the availability of nitrogen in the 75% guajillo diet. Phenolic amine and
      tannin concentrations increased (P<0.05) as level of guajillo in the diet
      increased. Glucuronic acid output in goats fed 75% guajillo was significantly
      (P<0.05) higher than the other diets, and suggests an increased requirement for
      liver glucose metabolism in goats consuming large amounts of guajillo. In the
      palatability trial, the same goats were fed 250g of each diet for 9 days in a
      cafeteria trial to determine the characteristics eliciting a proportional choice
      among the four diets. Total DMI was similar to the results of the first trial.
      However, intakes of particular diets decreased (P<0.05) with increasing level of
      guajillo. Despite an apparently desirable gross energy content of all the diets,
      those containing guajillo did not meet digestible energy requirements for
      maintenance and mohair production at moderate levels of activity and production,
      and although none of the diets appeared to be acutely toxic, the goats preferred
      the diets lower in guajillo.

PMID- 11295397
TI  - Comparison of different protocols used to induce and synchronize estrus cycle of
      Saanen goats.
AB  - The objective of the present study was to determine the efficiency of different
      protocols in inducing and synchronizing the estrus cycle of Saanen goats by using
      new or reused synchro-mate-B (SMB) and controlled internal drug release (CIDR) in
      combination with either equine chorionic gonadotrophin (eCG) or cloprostenol.
      Female goats (n=120) were divided at random into six groups of 20 animals each.
      In the T1-SMB group, the females were injected intramuscularly (i.m.) with 2.5mg
      estradiol valerate+1.5mg norgestomet and received a subcutaneous ear implant
      containing 2.0mg of norgestomet for 9 days. On the day of implant removal, the
      animals received 100IU of eCG and 0.05mg of cloprostenol. In the T2-SMB group,
      the animals were identically treated, except that the ear implant they received
      had been previously used in cattle. In the T3-SMB group, the treatment was
      identical to that for T1-SMB, but eCG was not administered. In the T1-CIDR group,
      the animals were treated for 9 days with an intravaginal device inpregnated with
      0.3g of progesterone and injected i.m. with 100IU of eCG and 0.05mg of
      cloprostenol on the day of implant removal. The animals of the T2-CIDR group were
      treated like those of the T1-CIDR group, except that the intravaginal implant
      they received had been previously used in goats. The animals of the T3-CIDR group
      were treated like those of the T1-CIDR group, but did not receive eCG. The
      percentages of estrus and fertility were 100/80% (T1-SMB), 90/80% (T2-SMB),
      75/75% (T3-SMB), 100/95% (T1-CIDR), 100/100% (T2-CIDR) and 70/65% (T3-CIDR),
      respectively, with the results for both parameters being lower (P</=0.05) in the
      T3-SMB and T3-CIDR groups. It is concluded that auricular implants or
      intravaginal devices may be reused, at last one more time, because they are
      efficient for inducing and synchronizing estrus in cyclic dairy goats.

PMID- 11295398
TI  - In vitro fermentation of cellulosis amorphous and meadow hay in experimentally
      Ascaris suum-infected lambs.
AB  - The objective of this experiment was to determine the effect of rumen inocula
      from experimentally Ascaris suum (AS)-infected lambs on cellulose amorphous (CA)
      and meadow hay (MH) used as substrates during 72h incubation in vitro. The rumen
      inocula were obtained post-mortem from eight lambs that had been experimentally
      infected with 1000 AS eggs per lamb daily for 3 weeks. Samples of rumen inocula
      were obtained from the lambs weekly throughout the experiment for 8 weeks. Two
      lambs were kept as uninfected control animals. The substrates were incubated
      together with buffered rumen fluid in sealed fermentation bottles. In vitro dry
      matter degradability (IVDMD), total gas, methane and total and individual fatty
      acid (VFA) for both incubated substrates were measured and compared by the
      pressure transducer technique. Comparison of the values for the controls, total
      gas, methane and VFA revealed significant differences (P<0.05, P<0.01, P<0.001,
      respectively) for both substrates. Pronounced differences (P<0.001) were also
      found between CA and MH especially for IVDMD, total gas and total VFA production.
      A decrease (P<0.001) of IVDMD, total gas, methane and total VFA was observed from
      week 6 to week 8. Restriction of fermentation was evident from week 7 to week 8.
      The results suggest that the functional damage arising from pathological lesions
      within the parasite-infected organs considerably affected the fermentation
      parameters of the incubated substrates.

PMID- 11295399
TI  - Fertilization and development of Caprine oocytes matured over granulosa cell
      monolayers.
AB  - The aim of the present study was to compare the two oocyte maturation systems,
      i.e. a granulosa cell (GC) monolayer from small (<4mm) or large (>4mm) follicles
      and a granulosa co-culture for their effects on in vitro maturation (IVM),
      fertilization and developmental competence of caprine oocytes. A total of 1945
      oocytes were used for studies on maturation, fertilization and embryo
      development. Monolayers were primed with maturation medium, 18-24h before the
      onset of maturation. Nuclear studies of 263 fertilized oocytes, 18h post
      fertilization, revealed that the rate of sperm penetration was not affected by
      any of the maturation culture systems. Penetration rate was 66.30% versus 69.59%
      for the control and GC monolayers. On the other hand, progression of
      fertilization, i.e. sperm head decondensation (32.70% versus 9.78%) and
      pronucleus formation (8.76% versus 2.17%) were significantly (P<0.05) enhanced in
      the oocytes matured over GC monolayers, compared to those with GC co-culture
      respectively. Cleavage rate was significantly (P<0.05) higher in the oocytes
      matured and cultured over GC monolayers (27.59%) compared to those in oocytes
      matured and cultured with the GC co-culture (19.28%). Proportionately more
      embryos derived from oocytes matured and cultured with the GC co-culture blocked
      (16.53 and 25.92%) at early developmental stages (2-cell and 4-cell,
      respectively), compared to those derived from oocytes matured and cultured over
      GC monolayers (7.61% versus 10.56%; 2-cell versus 4-cell). It was concluded that
      GC monolayers better support cytoplasmic maturation of growing caprine oocytes,
      which is evident by a better maturation rate, active fertilization, an improved
      cleavage rate and subsequently a higher rate of morula formation. Granulosa cells
      from small and large follicles can be used for IVM and IVC with approximately the
      same efficiency after conditioning them with maturation medium and embryo
      development medium 18-24h before the onset of culture.

PMID- 11295400
TI  - Effect of daily oxytocin injection on milk yield and lactation length in sheep.
AB  - The effects of daily oxytocin (OT) (2 IU) injection (i.m.) on lactation
      performance of 25 Mehraban ewes were studied. Eight control ewes were injected
      with 1ml of saline. Eight ewes were injected with OT after weaning (POT), and
      nine ewes were injected with OT from day 15 of lactation (WOT). Total milk
      production for WOT ewes was 55.5 and 24.7% greater (P<0.05) than for control and
      POT ewes, respectively. POT group produced 24.7% more milk than control group.
      Lactation length was 175 days for WOT and POT groups, and 143 days for control
      ewes. Daily milk yield after weaning was greater for WOT and POT as compared with
      control ewes. WOT lambs had a greater daily weight gain as compared with POT and
      control lambs. WOT ewes lost more weight during the suckling period, but the
      difference in ewe live weight loss after weaning was not significant between the
      experimental groups. Fat content as a percentage of milk dry matter was greater
      for WOT than for control and POT ewes. Milk density, pH, freezing point, and
      protein, lactose and ash contents were not affected by OT treatment. Somatic cell
      count (SCC) was greater for control than for POT and WOT groups and increased as
      lactation progressed. The results of this experiment support the hypothesis that
      OT may be involved in mammary cell maintenance and metabolism, in addition to
      causing myoepithelial cell contraction and milk letdown.

PMID- 11295401
TI  - Development of testicular dimensions and size, and their relationship to age,
      body weight and parental size in growing Awassi ram lambs.
AB  - Ninety-six Awassi ram lambs, aged 2-3 months, raised and managed under a semi
      intensive system were used to measure development of testicular length, width,
      circumference and volume, and their association with development of body growth.
      The effects of parental size, age and body weight of lambs, production line
      (dairy or meat), type of birth and weight at birth and weaning on development of
      the four testicular parameters from weaning at 2-17 months of age were
      investigated. No significant differences were observed between measurements of
      the left and right testis. The highest increase in testicular parameters occurred
      between 7 and 10 months of age at 34.6kg live body weight. Only parental size,
      age and body weight affected testicular growth (P<0.05). Measurements of testes
      were correlated (P<0.01) with each other (r=0.68-0.97). They increased
      progressively and were correlated with body weight more than with age.

PMID- 11295402
TI  - Some carcass characteristics of Alpine kids under intensive versus semi-intensive
      systems of production in France.
AB  - The effect of system of production (intensive versus semi-intensive) on some
      slaughter and carcass traits of Alpine male kids was evaluated. Data adjusted to
      a common age, indicated that management system had no significant effect (P>0.05)
      on carcass shape (carcass conformation and compactness and gigot conformation)
      and external fat score. Kids raised under the intensive management (IM) had
      heavier slaughter and carcass weights and large carcass width (P<0.01). Their
      dressing percentage and internal fat score were higher (P<0.05).

PMID- 11295403
TI  - Host pathogenesis in urinary tract infections.
AB  - Urinary tract infections (UTIs) are the result of an interaction between
      bacterial virulence and host defense factors that compete to invade or protect
      the host, respectively. Research over the past 30 years has demonstrated that
      vaginal colonization with uropathogens precedes most UTIs. Receptivity of the
      vaginal mucosa for uropathogens is an essential initial step in vaginal mucosa
      colonization. When vaginal and buccal epithelial cells were collected from
      patients susceptible to reinfection and compared with such cells obtained from
      controls resistant to UTIs, the strains that caused cystitis adhered much more
      avidly to the epithelial cells from susceptible women. These genotypic traits for
      epithelial cell receptivity may be a major susceptibility factor in UTIs. The
      presence or absence of blood group determinants on the surface of uroepithelial
      cells may influence an individual's susceptibility to UTIs. The protective effect
      in women with the secretor phenotype may be due to fucosylated structures at the
      cell surface which decrease the availability of putative receptors for
      Escherichia coli. Susceptibility among women who do not secrete blood group
      antigens may be due to specific E. coli-binding glycolipids that are absent in
      women who secrete blood group antigens. Recent studies have shown that the
      vaginal fluid, which forms an interface between uropathogens and epithelial
      cells, also influences vaginal colonizations.

PMID- 11295404
TI  - Secretion of cytokines by uroepithelial cells stimulated by Escherichia coli and
      Citrobacter spp.
AB  - Urinary tract epithelial cells (T 24/83) are able to express interleukin (IL)-6,
      IL-8, platelet-derived growth factor (PDGF) and tumour necrosis factor-alpha, but
      not IL-1 beta, IL-2, IL-4 and IL-10 in response to an infection with
      uropathogenic bacteria. The process of cytokine secretion is time dependent, with
      a significant increase in the cytokine activity after 60 min. The expression of
      virulence factors of the bacteria does not seem to play a role. The interaction
      between bacterial products (e.g. lipopolysaccharide) and/or bacterial adhesion
      mediated by adhesins and specific receptor molecules of cell surfaces may be
      responsible for the activity of mediator protein expression in the epithelial
      cells. The release of PDGF and IL-8 was found to be higher when due to
      Escherichia coli HB 101 (rough form) than that caused by other bacterial strains.
      Citrobacter CB 3009 provoked the highest level of IL-6. The PDGF level correlated
      significantly with IL-6 and IL-8 values (P<0.001). There was a significant
      correlation between the time-dependent release of IL-6 and IL-8 (P<0.05). In
      epithelial cytokine response to bacterial infection, the reaction of the
      epithelial cells may modify themselves (e.g. internalization of bacteria) and the
      immuno-regulatory processes that are caused by infection and responsible for
      parenchymal injury.

PMID- 11295405
TI  - Recurrent urinary tract infection in women.
AB  - Recurrent urinary tract infections (UTI) are common among young healthy women
      even though they generally have anatomically and physiologically normal urinary
      tracts. Women with recurrent UTI have an increased susceptibility to vaginal
      colonization with uropathogens, which is due to a greater propensity for
      uropathogenic coliforms to adhere to uroepithelial cells. Risk factors for
      recurrent UTI include sexual intercourse, use of spermicidal products, having a
      first UTI at an early age, and having a maternal history of UTIs. Inherited
      factors may be important in some women with recurrent UTI. Many factors thought
      to predispose to recurrent UTI in women, such as pre- and post-coital voiding
      patterns, frequency of urination, wiping patterns, and douching have not been
      proven to be risk factors for UTI. In contrast to the predominantly behavioral
      risk factors for young women, mechanical and/or physiological factors that affect
      bladder emptying are most strongly associated with recurrent UTI in healthy
      postmenopausal women. The management of recurrent UTI is the same as that for
      sporadic UTI except that the likelihood of infection with an antibiotic resistant
      uropathogen is higher in women who have received recent antimicrobials.
      Strategies to prevent recurrent UTI in young women should include education about
      the association of recurrent UTI with frequency of sexual intercourse and the
      usage of spermicide-containing products. Continuous or post-coital prophylaxis
      with low-dose antimicrobials or intermittent self-treatment with antimicrobials
      have all been demonstrated to be effective in managing recurrent uncomplicated
      UTIs in women. Estrogen use is very effective in preventing recurrent UTI in post
      menopausal women. Exciting new approaches to prevent recurrent UTI include the
      use of probiotics and vaccines. Further understanding of the pathogenesis of UTI
      will lead to more effective and safer methods to prevent these frequent
      infections.

PMID- 11295406
TI  - Postmenopausal women with recurrent UTI.
AB  - Urinary tract infection is a frequent disease in elderly women. The lack of
      estrogen, which characterizes the postmenopause, plays an important role in the
      pathogenesis of this infective disease. Exogenous estrogen replacement, however,
      is very effective in the prevention of bacteriuria in these women. The safety of
      oral and vaginal estriol and their efficacy in comparison to antimicrobial
      prophylaxis should be confirmed in the future.

PMID- 11295407
TI  - Urinary tract infection in pregnancy.
AB  - Urinary tract infection is one of the most frequently seen 'medical'
      complications in pregnancy. The pioneering work of Edward Kass discovered that 6%
      of pregnant women had asymptomatic bacteriuria associated with increased
      prematurity and perinatal mortality compared to women with sterile urine.
      Screening for bacteriuria in pregnancy has become routine. The prevalence of
      asymptomatic bacteriuria as well as the associated complications described by
      Kass in 1962 are higher compared to most data collected in the 1980s and late
      1990s in different populations in various parts of the world. Other factors such
      as vaginal colonization have been recognized as important contributors to preterm
      labour. The value of screening for bacteriuria has to be re-addressed considering
      methods, significance and costs. Treatment of urinary tract infection in
      pregnancy is critically reviewed.

PMID- 11295409
TI  - Use of antibiotics to treat bacteriuria of pregnancy in the Nordic countries.
      Which antibiotics are appropriate to treat bacteriuria of pregnancy?
AB  - Bacteriuria in pregnancy with or without clinical symptoms is frequent and
      increases the risk of pyelonephritis, preterm labour, and low birth weight
      infants. Commonly used antibiotics such as ampicillin (pivampicillin),
      amoxicillin, trimethoprim, and sulphonamide are currently associated with a high
      degree of resistance of the most common pathogen in the urinary tract,
      Escherichia coli. During the past few decades a number of new and efficient
      antibacterial antibiotics have been developed. The presumption that a specific
      drug is safe for both the pregnant woman and the foetus depends on how widely the
      drug has been used. A recent survey among general practitioners and obstetricians
      in Denmark, Finland, Norway, and Sweden confirmed that the beta-lactam antibiotic
      pivmecillinam and nitrofurantoin are the most commonly used agents in the
      treatment of bacteriuria in pregnancy in the Nordic countries. However, a
      surprisingly high number of physicians reported that they prescribe sulphonamides
      during the first two trimesters in spite of resistance of E. coli and possible
      adverse effects on the foetus.

PMID- 11295408
TI  - Treatment of lower urinary tract infection in pregnancy.
AB  - Urinary tract infection (UTI) is a common complication of pregnancy.
      Approximately 20--40% of women with asymptomatic bacteriuria will develop
      pyelonephritis during pregnancy. All pregnant women, therefore, should have their
      urine cultured at their first visit to the clinic. In a clinical study comparing
      single-dose treatment with 3 g fosfomycin trometamol versus a 3-day course of 400
      mg ceftibuten orally, the inclusion criteria were acute symptomatic lower UTI
      (acute cystitis), significant bacteriuria (> or =10(3) CFU/ml), pyuria and
      confirmed pregnancy. Excluded were patients with asymptomatic bacteriuria or
      acute pyelonephritis. Predisposing factors comprised a history of recurrent UTI,
      diabetes mellitus, analgesic nephropathy, hyperuricaemia or Fanconi's syndrome.
      Escherichia coli was the most frequently isolated pathogen in both groups.
      Therapeutic success (clinical cure and bacteriological eradication of
      uropathogens) was achieved in 95.2% of the patients treated with fosfomycin
      trometamol versus 90.0% of those treated with ceftibuten (P, non-significant).
      The treatment of acute cystitis in pregnant women using a single-dose of
      fosfomycin trometamol was equally effective as the 3-day course of oral
      ceftibuten. Both regimens were well tolerated with only minor adverse effects.
      Long-term chemoprophylaxis should be suggested in patients with recurrent UTI or
      following acute pyelonephritis during pregnancy.

PMID- 11295410
TI  - Urinary tract infections in adults with diabetes.
AB  - Urinary tract (UTI) is a major disease burden for many patients with diabetes.
      Asymptomatic bacteriuria is several-fold more common among women and acute
      plyelonephritis is five to ten times more common in both sexes. The complications
      of pyelonephritis are also more common in patients with diabetes. These
      complications include acute papillary necrosis, emphysematous pyelonephritis, and
      bacteremia with metastatic localization to other sites. The management of urinary
      infection in patients with diabetes is essentially the same as patients without
      diabetes. Most infections should be managed as uncomplicated except when they
      occur in a milieu with obstruction or other factors that merit a diagnosis of
      complicated UTI. Strategies to prevent these infections and reduce morbidity
      should be a priority for research.

PMID- 11295411
TI  - Urinary tract infection in neurogenic bladder.
AB  - The most frequent medical complication in patients with neurogenic bladder
      dysfunction is urinary tract infection (UTI). In the acute phase of neurogenic
      bladder, aseptic intermittent catheterization should be applied. After this
      phase, patients are subject to UTIs leading to febrile diseases. In the chronic
      phase of neurogenic bladders, febrile infections are often accompanied with
      hypertonic bladder. Some causes or symptoms prior to febrile attack are
      recognized in many of the cases. Antimicrobial chemotherapy has to be started in
      time without delay. Newer generation cephalosporins and carbapenems may shorten
      the febrile period. We report our experience with 229 patients treated between
      January 1993 and December 1998.

PMID- 11295412
TI  - Catheter-associated urinary tract infections.
AB  - Nosocomial urinary tract infection (UTI) is the most common infection acquired in
      both hospitals and nursing homes and is usually associated with catheterization.
      This infection would be even more common but for the use of the closed catheter
      system. Most modifications have not improved on the closed catheter itself. Even
      with meticulous care, this system will not prevent bacteriuria. After bacteriuria
      develops, the ability to limit its complications is minimal. Once a catheter is
      put in place, the clinician must keep two concepts in mind: keep the catheter
      system closed in order to postpone the onset of bacteriuria, and remove the
      catheter as soon as possible. If the catheter can be removed before bacteriuria
      develops, postponement becomes prevention.

PMID- 11295413
TI  - Catheter associated urinary tract infection and encrustation.
AB  - This paper examines the relationship between urinary pH, infection and urinary
      catheter encrustation and discusses the current management and problems of
      catheter associated urinary infection and encrustation.

PMID- 11295414
TI  - Catheter-associated urinary tract infections: impact of catheter materials on
      their management.
AB  - Infection associated with an indwelling catheter is a representative type of
      biofilm infection occurring in the urinary tract. Since the most effective way to
      control this intractable infection is the prevention of bacterial attachment and
      subsequent biofilm formation on the catheter, the importance of catheter
      materials and anti-bacterial coating cannot be underestimated. The difference in
      the degree of bacterial attachment among standard catheter materials, the
      efficacy of silver-coating of catheters in preventing infection and the potency
      and effectiveness of a new lecithin/silver coating are discussed.

PMID- 11295415
TI  - Oral fluoroquinolone therapy results in drug adsorption on ureteral stents and
      prevention of biofilm formation.
AB  - The oral administration of ciprofloxacin (250mg bid) and ofloxacin (300mg bid) in
      40 patients with ureteral stents, led to drug levels on all the device surfaces
      that were higher than the minimum inhibitory concentration (MIC) of Escherichia
      coli (0.004--0.015 mg/l), the most common uropathogen. The drug levels in the
      film were higher than the MIC of other common pathogens, namely Pseudomonas
      aeruginosa (0.25--1.0 mg/l), Enterococcus faecalis (0.25--2.0 mg/l) and
      Staphylococcus aureus (0.12--0.5 mg/l) in a few cases (six, three and 14 cases
      out of 40, respectively). For both antibiotics, the concentrations were greater
      than the MIC of many uropathogens on the film surrounding the devices (0.89 vs
      0.31 mg/l respectively, P=0.05), and on the devices themselves (0.22 vs. 0.12
      mg/l, P=0.207). Adsorption of the antibiotics was higher to the film than to the
      stent (P<0.0001). Ciprofloxacin concentration on the film surrounding the stents
      was significantly higher than that of ofloxacin (P=0.05), while there was no
      statistical concentration difference between the two antibiotics adsorbed onto
      the actual devices (P=0.207). No bacteria were found in patients' urine and no
      biofilms were detected. This is the first report of an oral antibiotic being
      adsorbed onto medical devices. It potentially provides a new approach of
      preventing infection, and avoids the need to pre-coat devices with agents whose
      use will be restricted once bacteria develop resistance to them. If biomaterial
      properties can be enhanced to increase further the adsorptive concentration of
      drug, the risk of infections and recalcitrant biofilm formation could be
      significantly reduced in a highly susceptible patient population.

PMID- 11295416
TI  - Guidelines for the perioperative prophylaxis in urological interventions of the
      urinary and male genital tract.

PMID- 11295417
TI  - Staphylococcus aureus bacteriuria and surgical site infections by methicillin
      resistant Staphylococcus aureus.
AB  - Surgical site infection (SSI) remains an important cause of morbidity among
      hospitalized patients. We reviewed 421 patients who underwent open urological
      operations between January 1993 and December 1997 in our institute. Group I
      consisted of 259 patients who received uncontrolled antimicrobial prophylaxis
      (AMP) between 1993 and 1995. Group II consisted of 162 patients who received
      controlled AMP between 1996 and 1997. In group II, penicillins or first to second
      generation cephalosporins was used and the duration of use for these agents
      regulated according to the wound class of each operation. The operations with
      clean wounds showed the lowest rate of SSI in both groups; the operations with
      contaminated wounds showed the highest rate of SSI (32.0% in group I and 33.3% in
      group II). There was no significant difference in the total rates of SSI between
      the two groups (P=0.216). The most frequently isolated bacterial species was
      methicillin-resistant Staphylococcus aureus (MRSA), isolated in 73.3% of the
      cases in group I and in 93.3% in group II. There was no significant difference in
      the incidence of MRSA isolation between the two groups (P=0.114). The controlled
      AMP could not lower the incidence of MRSA-induced SSIs. In SSI patients, 22.7% of
      group I and 35.7% in group II, had MRSA bacteriuria before operation. The
      prohibition of third-generation cephalosporins and shorter duration of AMP did
      not reduce the incidence of SSI induced by MRSA because MRSA was not the emerging
      microorganism but rather a resident in the urological ward. On the other hand,
      the total incidence of SSI did not increase after regulation of AMP. This finding
      suggests that older antibacterial agents can prevent infection, except those
      caused by resistant microorganisms such as MRSA. The effective counter-measure
      for the prevention of MRSA-induced SSI is needed.

PMID- 11295418
TI  - Which fluoroquinolones are suitable for the treatment of urinary tract
      infections?
AB  - A number of fluoroquinolone agents are now available for clinical use and even
      more under development. Whether these compounds are equally effective and thus
      interchangeable in the treatment of urinary tract infection (UTI) has to be
      answered by comparing their antimicrobial activity against uropathogens, the
      pharmacokinetic and pharmacodynamic parameters and outcome of statistically
      meaningful clinical studies. Whereas almost all fluoroquinolones give equivalent
      results with short term therapy of acute uncomplicated cystitis in women, for
      patients with complicated UTI, only those compounds at the appropriate dosage
      regimen should be chosen for empiric therapy, which would exhibit sufficiently
      high urinary bactericidal activity against Gram-negative as well as Gram-positive
      uropathogens. When considering antibacterial activity, pharmacokinetic and
      pharmacodynamic properties as well as the results of the published clinical
      studies, a dosage of 500 mg ciprofloxacin twice daily, 500 mg levofloxacin once
      daily, or 400 mg gatifloxacin once daily may be comparable dosage regimens in the
      treatment of severe complicated UTI. In the case of ciprofloxacin (750 mg twice
      daily) and levofloxacin (500 mg twice daily), the dose could even be increased in
      UTI caused by less susceptible uropathogens, such as Pseudomonas aeruginosa.

PMID- 11295419
TI  - Urinary tract infection in adults: research priorities and strategies.
AB  - Waning interest in urinary tract infection (UTI) research has limited clinical
      advances during the past two decades. Although care has improved for some
      specific UTI syndromes, there is limited evidence for most of the decisions made
      each day in the management of these infections. Additional clinical research is
      necessary to improve UTI prevention and care strategies.

PMID- 11295420
TI  - Kinetic characterization of hexokinase isoenzymes from glioma cells: implications
      for FDG imaging of human brain tumors.
AB  - Quantitative imaging of glucose metabolism of human brain tumors with PET
      utilizes 2-[(18)F]-fluorodeoxy-D-glucose (FDG) and a conversion factor called the
      lumped constant (LC), which relates the metabolic rate of FDG to glucose. Since
      tumors have greater uptake of FDG than would be predicted by the metabolism of
      native glucose, the characteristic of tumors that governs the uptake of FDG must
      be part of the LC. The LC is chiefly determined by the phosphorylation ratio
      (PR), which is comprised of the kinetic parameters (Km and Vmax) of hexokinase
      (HK) for glucose as well as for FDG (LC proportional to (Km(glc) x
      Vmax(FDG))/(Km(FDG) x Vmax(glc)). The value of the LC has been estimated from
      imaging studies, but not validated in vitro from HK kinetic parameters. In this
      study we measured the kinetic constants of bovine and 36B-10 rat glioma HK I
      (predominant in normal brain) and 36B-10 glioma HK II (increased in brain tumors)
      for the hexose substrates glucose, 2-deoxy-D-glucose (2DG) and FDG. Our principal
      results show that the KmGlc < KmFDG << Km2DG and that PR2DG < PRFDG. The FDG LC
      calculated from our kinetic parameters for normal brain, possessing predominantly
      HK I, would be higher than the normal brain LC predicted from animal studies
      using 2DG or human PET studies using FDG or 2DG. These results also suggest that
      a shift from HK I to HK II, which has been observed to increase in brain tumors,
      would have little effect on the value of the tumor LC.

PMID- 11295421
TI  - Characterization of acetate metabolism in tumor cells in relation to cell
      proliferation: acetate metabolism in tumor cells.
AB  - To reveal the metabolic fate of acetate in neoplasms that may characterize the
      accumulation patterns of [1-(11)C]acetate in tumors depicted by positron emission
      tomography. Four tumor cell lines (LS174T, RPMI2650, A2780, and A375) and
      fibroblasts in growing and resting states were used. In uptake experiments, cells
      were incubated with[1-(14)C]acetate for 40 min. [(14)C]CO(2) was measured in the
      tight-air chamber, and the metabolites in cells were identified by thin layer
      chromatography and paper chromatography. The glucose metabolic rate of each cell
      line was measured with [2,6-(3)H]2-deoxy-glucose (DG), and the growth activity of
      each cell line was estimated by measuring the incorporation of [(3)H]methyl
      thymidine into DNA. Compared with resting fibroblasts, all four tumor cell lines
      showed higher accumulation of (14)C activity from [1-(14)C]acetate. These tumor
      to-normal ratios of [1-(14)C]acetate were larger than those of DG. Tumor cells
      incorporated (14)C activity into the lipid-soluble fraction, mostly of
      phosphatidylcholine and neutral lipids, more prominently than did fibroblasts.
      The lipid-soluble fraction of (14)C accumulation in cells showed a positive
      correlation with growth activity, whereas the water-soluble and CO(2) fractions
      did not. These findings suggest that the high tumor-to-normal ratio of [1
      (14)C]acetate is mainly due to the enhanced lipid synthesis, which reflects the
      high growth activity of neoplasms. This in vitro study suggests that [1
      (11)C]acetate is appropriate for estimating the growth activity of tumor cells.

PMID- 11295422
TI  - Characterization of 3-[123I]iodo-L-alpha-methyl tyrosine ([123I]IMT) transport
      into human Ewing's sarcoma cells in vitro.
AB  - 3-[(123)I]Iodo-L-alpha-methyl tyrosine ([(123)I]IMT) scintigraphy of extracranial
      malignant tumors has been described, but little is known about the transport
      systems involved in [(123)I]IMT uptake into extracranial tumor cells. Here, the
      precise kinetics of [(123)I]IMT transport into human Ewing's sarcoma cells (VH
      64) was determined. The apparent Michaelis constant was of high affinity value
      (K(m)=41.7+/-3.9 microM) and maximum transport velocitiy amounted to
      V(max)=20.7+/-0.6 nmol x mg protein(-1) x 10 min(-1). Inhibition experiments
      revealed the predominance of [(123)I]IMT uptake via sodium-independent system L.

PMID- 11295423
TI  - In vitro characterization of the influx of 3-[125I]iodo-L-alpha-methyltyrosine
      and 2-[125I]iodo-L-tyrosine into U266 human myeloma cells: evidence for system T
      transport.
AB  - The aim of this study was to investigate the cellular uptake mechanisms
      responsible for the accumulation of 3-[(125)I]iodo-L-alpha-methyltyrosine ((125)I
      3-IMT) and 2-[(125)I]iodo-L-tyrosine ((125)I-2-IT), two radiotracers for
      metabolic tumor imaging, using single-photon emission tomography, into U266 human
      myeloma cancer cells. Time course and concentration dependency of (125)I-3-IMT
      uptake was assessed. Kinetic parameters were calculated using an Eadie Hofstee
      plot. A set of competitive inhibitors of the main amino acid transport systems
      was used for the discrimination of the transporters responsible for the uptake of
      (125)I-3-IMT and (125)I-2-IT. Protein incorporation of both tracers was
      determined using acid precipitation. The measured maximum velocity for (125)I-3
      IMT transport was 4.199 nmol per mg protein 20 s(-1), and the Michaelis constant
      was 107.9 microM. Addition of 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid
      (BCH), a competitive inhibitor of System L, reduced the influx by 39.0+/-3.3% for
      (125)I-3-IMT and 66.3+/-0.9% for (125)I-2-IT. The BCH-insensitive influx was
      further reduced by Tryptophan (Trp) by 43.8+/-3.5% for (125)I-3-IMT and 15.3+/
      1.3% for (125)I-2-IT. This suggests involvement of System T transport. We
      measured <2% of radioactivity in the acid precipitable fractions of both tracers
      with no increase in time. We conclude that the influx of (125)I-3-IMT and (125)I
      2-IT into U266 human myeloma cells is mediated by both System L and System T
      amino acid transporters. The kinetic parameters suggest that elevated plasma
      levels of aromatic amino acids will reduce (123)I-3-IMT uptake in myeloma
      patients. Both tracers do not enter protein synthesis significantly.

PMID- 11295424
TI  - Simultaneous evaluation of dual gene transfer to adherent cells by gamma-ray
      imaging.
AB  - A gamma camera imaging method was developed to detect dual gene transfer to
      adherent cells growing as monolayers in cell culture plates. Human cancer cells
      were infected with replication-incompetent adenoviral vectors encoding the human
      type 2 somatostatin receptor (Ad-hSSTr2) and/or herpes virus thymidine kinase (Ad
      TK). The hSSTr2 and TK reporter proteins were detected by imaging internally
      bound (99m)Tc-P2045 peptide (Diatide, Inc.) and radioiodinated 2'-deoxy-2'-fluoro
      beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Following gene
      transfer, expression of hSSTr2 and TK were accurately imaged in vitro.

PMID- 11295425
TI  - Development of an in vitro model for assessing the in vivo stability of
      lanthanide chelates.
AB  - An in vitro model was developed to evaluate the in vivo stability of lanthanide
      polyaminocarboxylate complexes. The ligand-to-metal ratios for the chelates EDTA,
      CDTA, DTPA, MA-DTPA (monoamide-DTPA) and DOTA with the lanthanides lanthanum,
      samarium, and lutetium were optimized to achieve > or = 98% complexation yield
      for the resultant radiolanthanide complexes. The exchange of the radiolanthanides
      from their EDTA, CDTA, DTPA, MA-DTPA and DOTA complexes with Ca(2+) was
      determined by in vitro adsorption and in vitro column studies using
      hydroxyapatite (HA), an in vitro bone model. In vitro serum stability of these
      radiolanthanide complexes was used as an additional indicator of in vivo
      stability, although the mechanism of instability in serum will be different than
      with bone. The in vitro studies were consistent with the expected findings that
      the smallest lanthanide (Lu) formed the most stable complexes. In vivo studies
      were done to validate the in vitro model. Biodistribution studies in normal CF-1
      mice showed that in vivo stability of the complex (i.e., the more lanthanide
      remaining in complex form) could be assessed by a combination of the urinary,
      bone and liver uptake. For example, biodistribution studies demonstrate that high
      urinary excretion correlated with complex stability, while high liver plus bone
      uptake correlated with complex instability. The urinary excretion of the EDTA
      complexes decreased from (177)Lu to (140)La indicating a loss in stability in the
      direction of (140)La, consistent with the in vitro studies. The more stable a
      lanthanide complex is, the lower its exchange with HA in vitro will be, and the
      lower its combined bone plus liver uptake and higher its urinary excretion will
      be in vivo. This investigation indicates that the in vivo stability can be
      determined by a screening method that measures the degree of exchange from the
      lanthanide chelate with hydroxyapatite (HA) and its serum stability.

PMID- 11295426
TI  - Plasma protein binding of (99m)Tc-labeled hydrazino nicotinamide derivatized
      polypeptides and peptides.
AB  - 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) constitutes one of the most
      attractive reagents to prepare (99m)Tc-labeled polypeptides and peptides of
      various molecular weights in combination with two tricine molecules as coligands.
      Indeed, (99m)Tc-HYNIC-conjugated IgG showed biodistribution of radioactivity
      similar to that of (111)In-DTPA-conjugated IgG. However, recent studies indicated
      significant plasma protein binding when the (99m)Tc labeling procedure was
      expanded to low molecular weight peptides. In this study, pharmacokinetics of
      (99m)Tc-HYNIC-conjugated IgG, Fab and RC160 using tricine were compared with
      their radioiodinated counterparts to evaluate this (99m)Tc-labeling method. In
      mice, [(99m)Tc](HYNIC-IgG)(tricine)(2) and [(99m)Tc](HYNIC-Fab)(tricine)(2)
      showed persistent localization of radioactivity in tissues when compared with
      their (125)I-labeled counterparts. [(99m)Tc](HYNIC-IgG)(tricine)(2) eliminated
      from the blood at a rate similar to that of (125)I-labeled IgG, while
      [(99m)Tc](HYNIC-Fab)(tricine)(2) showed significantly slower clearance of the
      radioactivity than (125)I-labeled Fab. On size-exclusion HPLC analyses, little
      changes were observed in radiochromatograms after incubation of [(99m)Tc](HYNIC
      IgG)(tricine)(2) in murine plasma. However, [(99m)Tc](HYNIC-Fab)(tricine)(2) and
      [(99m)Tc](HYNIC-RC160)(tricine)(2) demonstrated significant increases in the
      radioactivity in higher molecular weight fractions in plasma. Formation of higher
      molecular weight species was reduced when [(99m)Tc](HYNIC-RC160)(tricine)(2) was
      stabilized with nicotinic acid (NIC) to generate [(99m)Tc](HYNIC
      RC160)(tricine)(NIC). [(99m)Tc](HYNIC-RC160)(tricine)(NIC) also demonstrated
      significantly faster clearance of the radioactivity from the blood than
      [(99m)Tc](HYNIC-RC160)(tricine)(2). These findings suggested that one of the
      tricine coligands in (99m)Tc-HYNIC-labeled (poly)peptides would be replaced with
      plasma proteins to generate higher molecular weight species that exhibit slow
      blood clearance. In addition, the molecular sizes of parental peptides played an
      important role in the progression of the exchange reaction of one of the tricine
      coligands with plasma proteins.

PMID- 11295427
TI  - In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine
      treatment in baboon using SPECT.
AB  - To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT
      studies were performed with 5-[(123)I]-iodo-A-85380 in baboons pre and post
      chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine
      at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of
      27.3 ng/mL. This is equivalent to that found in an average human smoker (20
      cigarettes a day). In the baboon brain the regional distribution of 5-[(123)I]
      iodo-A-85380 was consistent with the known densities of nAChRs (thalamus >
      frontal cortex > cerebellum). Changes in nAChR binding were estimated from the
      volume of distribution (V(d) ) and binding potential (BP) derived from 3
      compartment model fits. In the (-)-nicotine treated animal V(d) was significantly
      increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of
      (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33%
      increase in the frontal cortex failed to reach significance. A significant
      increase in BP was seen in the thalamus. In the saline control animal no changes
      were observed in V(d) or BP under any experimental conditions. In this
      preliminary study, we have demonstrated for the first time in vivo upregulation
      of neuronal nAChR binding following chronic (-)-nicotine treatment.

PMID- 11295428
TI  - New halogenated [11C]WAY analogues, [11C]6FPWAY and [11C]6BPWAY--radiosynthesis
      and assessment as radioligands for the study of brain 5-HT1A receptors in living
      monkey.
AB  - [Carbonyl-(11)C]WAY-100635 ([(11)C]WAY) is an established radioligand for the
      study of brain serotonin(1A) (5-HT(1A)) receptors in living animals and humans
      with positron emission tomography (PET). There is a recognised need to develop
      halogenated ligands for 5-HT(1A) receptors, either for labelling with longer
      lived fluorine-18 for more widespread application with PET or with iodine-123 for
      application with single photon emission tomography (SPET). Here we used
      autoradiography and PET to assess two new halogenated analogues of WAY, namely
      6BPWAY and 6FPWAY [N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl))-N-(2-(6-bromo
      /fluoro-pyridinyl))cyclohexanecarboxamide] as prospective radioligands, initially
      using carbon-11 as the radiolabel. Labelling of 6BPWAY and 6FPWAY with carbon-11
      was accomplished by acylation of the corresponding secondary amine precursors
      with [carbonyl-(11)C]cyclohexanecarbonyl chloride. After incubation of human
      brain crysections with [(11)C]6BPWAY or [(11)C]6FPWAY, the highest accumulation
      of radioactivity was observed in cortical areas and the hippocampal formation.
      Both radioligands had high nonspecific binding. There was a rapid accumulation of
      radioactivity in the monkey brain after intravenous injection of [(11)C]6BPWAY
      and [(11)C]6FPWAY. High accumulation of radioactivity was observed in the frontal
      and temporal cortex and the raphe nuclei, areas known to contain a high density
      of 5-HT(1A) receptors. The ratios of radioactivity in receptor-rich temporal
      cortex to that in receptor-poor cerebellum at peak equilibrium were 1.9 (at 10
      min) and 3.0 at (at 20 min) for [(11)C]6BPWAY and [(11)C]6FPWAY, respectively. In
      pretreatment experiments with high doses of unlabelled WAY, the level of
      radioactivity in the frontal and temporal cortex and the raphe nuclei was reduced
      to the same level as in the cerebellum. Radioactive metabolites of [(11)C]6FPWAY
      appeared at a rate similar to those for [(11)C]WAY, with 17% of the radioactivity
      in plasma represented by unchanged radioligand after 40 min. Radioactive
      metabolites of [(11)C]6BPWAY appeared much more slowly. At 40 min after injection
      45% of the radioactivity in plasma still represented unchanged radioligand. The
      results indicate that 6-pyridinyl radiohalogented analogues of WAY are new leads
      to radioligands for PET or SPET.

PMID- 11295429
TI  - Synthesis and characterization of fluorinated and iodinated pyrrolopyrimidines as
      PET/SPECT ligands for the CRF1 receptor.
AB  - Fluorine-18 labeled fluorobutyl[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo
      [2,3-d] pyrimidin-4-yl]ethylamine (FBPPA) and iodine-123 labeled butyl[2,5
      dimethyl-7-(4-iodo-2,6-dimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethyl
      amine (IBPPA) were synthesized in the development of a CRF receptor ligand. The
      methods of synthesis, in vitro binding assays, radiolabeling and in vivo tissue
      distribution in rats are described. Fluorine-18 labeled FBPPA was prepared with
      high specific activity (3 x 10(4) Ci/mmol) by nucleophilic displacement with an
      average radiochemical yield of 6% (EOB). Iodine-123 labeled IBPPA was prepared by
      electrophilic iododestannylation with good yield (60%) and high specific activity
      (3.3 x 10(3) Ci/mmol). The retention of FBPPA and IBPPA in the pituitary was good
      (1.16% i.d./g and 2.35% i.d./g respectively at 60 min). However, the accumulation
      of radioactivity in the brain for both radiotracers was very low at all time
      points of the study, which demonstrated the difficulties for these
      radiopharmaceuticals to penetrate the blood brain barrier (BBB).

PMID- 11295430
TI  - Lipiodol solution of a lipophilic agent, (188)Re-TDD, for the treatment of liver
      cancer.
AB  - Radiolabeled lipiodol has been used for targeting liver cancer. We developed a
      lipiodol solution of (188)Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10
      decanedithiol) and investigated its feasibility for the treatment of liver
      cancer. The lipiodol solution of (188)Re-TDD was well-retained in the lipiodol
      phase in vitro. After injection through the tail veins of mice, high lung-uptake
      was investigated which is evidence of embolizing activity. We also found high
      accumulation in hepatoma after injection through the hepatic arteries of hepatoma
      bearing rats. In conclusion, the lipiodol solution of (188)Re-TDD is a promising
      agent for liver cancer therapy.

PMID- 11295431
TI  - Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution
      pattern in animal models.
AB  - The syntheses of four alpha-aminomethyl phosphonates and their complexation
      studies with (99m)Tc and (186/188)Re are reported. Complexation conditions were
      standardized to give maximum yields, which ranged from 90-97%. The yields of
      complexation were estimated by paper chromatography. The (99m)Tc complexes were
      stable for more than 4 h, while the (186/188)Re complexes were stable for 3-8
      days when stored at 4 degrees C. Biodistribution of these complexes in Wistar
      rats were carried out, and the uptake in bone and other soft tissue are detailed.
      Bone uptake of the (99m)Tc complexes varied from 40-60% at 30 min postinjection
      depending on the ligands. The uptake in soft tissue was minimum with all the
      complexes. A comparison of the biodistribution studies of the (99m)Tc complexes
      with that of the well-established radiopharmaceutical (99m)Tc-MDP was carried out
      for the purpose of evaluating the efficacy of the radiopharmaceutical preparation
      with the complexes of these ligands. The bone uptake of the (186/188)Re complexes
      varied from 19-28% corresponding to 1.6-3% per g at 3 h postinjection. The
      residual activity in both (99m)Tc and (186/188)Re complexes showed renal
      clearance.

PMID- 11295432
TI  - Calcium-induced changes in chondroitin sulfate chains of urinary trypsin
      inhibitor.
AB  - Urinary trypsin inhibitor (UTI) has several roles other than protease inhibition.
      It is suggested that UTI inhibits calcium influx in cultured cells and that the
      chondroitin sulfate chain of UTI may play an important role. In order to clarify
      the mechanistic features of this phenomenon, the chondroitin sulfate chain of UTI
      was analyzed by (1)H-NMR. The samples were highly purified UTI dissolved in D(2)O
      in the presence or absence of Ca(2+), Mg(2+) and Na(+). 1D-spectra were obtained
      and T(1) values of detected signals were estimated from the inversion-recovery
      method. The addition of Ca(2+) to UTI caused a chemical shift to downfield, line
      broadening and a reduction of T(1) values at several signals from chondroitin
      sulfate moiety (especially at axial H-2 of GalNAc), whereas Mg(2+) and Na(+) had
      no significant effect. Some of the signals in the linkage region of chondroitin
      sulfate chain showed marked line broadening by Ca(2+). The reduction of T(1)
      values implies formation of a complex. It is suggested that Ca(2+) generates the
      sulfate salt and interacts with other polar groups in the chondroitin sulfate
      chain, thereby causing bridging between UTI molecules. Several properties of UTI
      may be related to this interaction of Ca(2+) with chondroitin sulfate chains.

PMID- 11295433
TI  - Recombinant tyrosine aminotransferase from Trypanosoma cruzi: structural
      characterization and site directed mutagenesis of a broad substrate specificity
      enzyme.
AB  - The gene encoding tyrosine aminotransferase (TAT, EC 2.6.1.5) from the parasitic
      protozoan Trypanosoma cruzi was amplified from genomic DNA, cloned into the
      pET24a expression vector and functionally expressed as a C-terminally His-tagged
      protein in Escherichia coli BL21(DE3)pLysS. Purified recombinant TAT exhibited
      identical electrophoretic and enzymatic properties as the authentic enzyme from
      T. cruzi. Both recombinant and authentic T. cruzi TATs were highly resistant to
      limited tryptic cleavage and contained no disulfide bonds. Comprehensive analysis
      of its substrate specificity demonstrated TAT to be a broad substrate
      aminotransferase, with leucine, methionine as well as tyrosine, phenylalanine,
      tryptophan and alanine being utilized efficiently as amino donors. Valine,
      isoleucine and dicarboxylic amino acids served as poor substrates while polar
      aliphatic amino acids could not be transaminated. TAT also accepted several 2
      oxoacids, including 2-oxoisocaproate and 2-oxomethiobutyrate, in addition to
      pyruvate, oxaloacetate and 2-oxoglutarate. The functionality of the expression
      system was confirmed by constructing two variants; one (Arg389) being a
      completely inactive enzyme; the other (Arg283) retaining its full activity, as
      predicted from the recently solved three-dimensional structure of T. cruzi TAT.
      Thus, only one of the two strictly conserved arginines which are essential for
      the enzymatic activity of subfamily Ialpha aspartate and aromatic
      aminotransferases is critical for T. cruzi's TAT activity.

PMID- 11295434
TI  - In vitro dephosphorylation of alpha-crystallin is dependent on the state of
      oligomerization.
AB  - alphaA- and alphaB-crystallin, members of the small heat shock protein family,
      are present in lens cell extracts as large aggregates. Both alpha-crystallins are
      found partially phosphorylated. This study tests the ability of five phosphatases
      (protein phosphatase PP1, PP2A, PP2B, alkaline and acid phosphatases) to
      dephosphorylate alphaA- and alphaB-crystallin in vitro. Activity of a phosphatase
      was dependent on the size of the aggregate. Each of the phosphatases tested
      showed different specificity and efficiency towards alphaA- and alphaB
      crystallins, which depended on the oligomeric state of the alpha-crystallin
      aggregate. Alkaline phosphatase dephosphorylated both alphaA- and alphaB
      crystallin. The reaction was faster when alpha-crystallin was in a tetrameric
      form. PP2A dephosphorylated primarily alphaA-crystallin but only after the
      conversion of alpha-crystallin to tetramers. PP1 and PP2B did not dephosphorylate
      either alphaA- or alphaB-crystallins present as large aggregates but could not be
      tested on the lower molecular weight form of alphaA-crystallin. Acid phosphatase
      dephosphorylated both alphaA- and alphaB-crystallin. The results suggest that an
      important relationship exists between the structure of alpha-crystallin and its
      level of phosphorylation in the cell.

PMID- 11295435
TI  - Creatine kinase: a role for arginine-95 in creatine binding and active site
      organization.
AB  - Sequence homology analysis reveals that arginine-95 is fully conserved in 29
      creatine kinases sequenced to date, but fully conserved as a tyrosine residue in
      16 arginine kinases. Site-directed mutants of rabbit muscle creatine kinase
      (rmCK) were prepared in which R95 was replaced by a tyrosine (R95Y), alanine
      (R95A), or lysine (R95K). Kinetic analysis of phosphocreatine formation for each
      purified mutant showed that recombinant native rmCK and all R95 mutants follow a
      random-order, rapid-equilibrium mechanism. However, we observed no evidence for
      synergism of substrate binding by the recombinant native enzyme, as reported
      previously [Maggio et al., (1977) J. Biol. Chem. 252, 1202-1207] for creatine
      kinase isolated directly from rabbit muscle. The catalytic efficiencies of R95Y
      and R95A are reduced approximately 3000- and 2000-fold, respectively, compared to
      native enzyme, but that of R95K is reduced only 30-fold. The major contribution
      to the reduction of the catalytic efficiency of R95K is a 5-fold reduction in the
      affinity for creatine. This suggests that while a basic residue is required at
      position 95 for optimal activity, R95 is not absolutely essential for binding or
      catalysis in CK. R95Y has a significantly lower affinity for creatine than the
      native enzyme, but it also displays a somewhat lower affinity for MgATP and 100
      fold reduction in k(cat). Interestingly, R95A appears to bind either creatine or
      MgATP first with affinities similar to those for the native enzyme, but it has a
      10-fold lower affinity for the second substrate, suggesting that replacement of
      R95 by an alanine disrupts the active site organization and reduces the
      efficiency of formation of the catalytically competent ternary complex.

PMID- 11295436
TI  - Rapeseed chloroplast thioredoxin-m. Modulation of the affinity for target
      proteins.
AB  - The stroma of higher plant chloroplasts contains two thioredoxins (Trx) with
      different specificity for the reduction of protein disulfide bonds. Based upon
      electrostatic features of domains that participate in the thiol/disulfide
      exchange, we prepared mutants of rapeseed Trx-m bearing opposite charges at a
      single position and subsequently analyzed their action on the activation of
      rapeseed chloroplast fructose 1,6-phosphate (CFBPase). The replacement of Pro-35
      with lysine and glutamic residues enhanced and impaired, respectively, the
      stimulation of CFBPase relative to the wild-type and the P35A mutant.
      Furthermore, the shielding of electrostatic interactions with high concentrations
      of KCl greatly increased and concurrently made indistinguishable the affinity of
      all variants for CFBPase. The capacity to stimulate the enzyme activity likewise
      was enhanced concertedly by fructose-1,6-bisphosphate and Ca(2+) but, at variance
      with the action of KCl, remained sensitive to charges in the side chain of
      mutants. These results were consistent with a mechanism in which intermolecular
      electrostatic interactions and intramolecular non-covalent interactions control
      the formation of the non-covalent complex between reduced Trx and oxidized
      CFBPase and, in so doing, modulate the thiol/disulfide exchange.

PMID- 11295437
TI  - Insights into the reaction mechanism of the diisopropyl fluorophosphatase from
      Loligo vulgaris by means of kinetic studies, chemical modification and site
      directed mutagenesis.
AB  - Kinetic measurements, chemical modification and site-directed mutagenesis have
      been employed to gain deeper insights into the reaction mechanism of the
      diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris. Analysis of the
      kinetics of diisopropyl fluorophosphate hydrolysis reveals optimal enzyme
      activity at pH >/=8, 35 degrees C and an ionic strength of 500 mM NaCl, where
      k(cat) reaches a limiting value of 526 s(-1). The pH rate profile shows that full
      catalytic activity requires the deprotonation of an ionizable group with an
      apparent pK(a) of 6.82, DeltaH(ion) of 42 kJ/mol and DeltaS(ion) of 9.8 J/mol K
      at 25 degrees C. Chemical modification of aspartate, glutamate, cysteine,
      arginine, lysine and tyrosine residues indicates that these amino acids are not
      critical for catalysis. None of the six histidine residues present in DFPase
      reacts with diethyl pyrocarbonate (DEPC), suggesting that DEPC has no
      accessibility to the histidines. Therefore, all six histidine residues have been
      individually replaced by asparagine in order to identify residues participating
      in catalysis. Only substitution of H287 renders the enzyme catalytically almost
      inactive with a residual activity of approx. 4% compared to wild-type DFPase. The
      other histidine residues do not significantly influence the enzymatic activity,
      but H181 and H274 seem to have a stabilizing function. These results are
      indicative of a catalytic mechanism in which H287 acts as a general base catalyst
      activating a nucleophilic water molecule by the abstraction of a proton.

PMID- 11295438
TI  - Isolation and spectroscopic characterization of the structural subunits of
      keyhole limpet hemocyanin.
AB  - Keyhole limpet hemocyanin is a respiratory glycoprotein of high molecular weight
      from the gastropod mollusc Megathura crenulata. Two subunits, KLH1 and KLH2, were
      isolated using ion exchange chromatography and their physical properties are
      compared with the parent molecule. The various proteins are characterized by
      fluorescence spectroscopy, combined with fluorescence quenching studies, using
      acrylamide, cesium chloride and potassium iodide as tryptophan quenchers. The
      conformational stability of the native aggregate and its isolated structural
      subunits are also studied by circular dichroism and fluorescence spectroscopy as
      a function of temperature, as well as in the presence of guanidinium
      hydrochloride and urea. The associated subunits in the hemocyanin aggregates
      increase considerably the melting temperature to 67 degrees C and the free energy
      of stabilization in water, DeltaG(H(2)O)(D), towards guanidinium hydrochloride is
      higher for the decamer as compared to the isolated subunits; this difference can
      be accounted for by the stabilizing effects of intra-subunit interactions exerted
      within the oligomer. The copper-dioxygen complex at the active site additionally
      stabilizes the molecule, and removing of the copper ions increases the tryptophan
      emission and the quantum yield of the fluorescence.

PMID- 11295439
TI  - Flunitrazepam, a 7-nitro-1,4-benzodiazepine that is unable to bind to the indole
      benzodiazepine site of human serum albumin.
AB  - Benzodiazepine (BDZ) is generally thought to bind to site II of human serum
      albumin (HSA), also known as the indole-BDZ site, which is located at subdomain
      III A of the molecule. However, differences in the binding characteristics of BDZ
      drugs with HSA have been reported. The photolabeling profiles of HSA with
      [(3)H]flunitrazepam (FNZP) in the presence and absence of diazepam (DZP) were
      shown to be identical, suggesting that each drug primarily binds to different
      regions. The results of fluorescent probe displacement experiments showed that
      FNZP failed to decrease the fluorescence of dansylsarcosine to an extent similar
      to that of DZP. In the photoinhibition experiment, site I and site II ligands
      failed to inhibit the photoincorporation of [(3)H]FNZP to HSA. In order to
      evaluate the photolabeling specificity of FNZP, an attempt was made to photolabel
      alpha(1)-acid glycoprotein (AGP) which also binds BDZ with similar affinity as
      HSA. The effect of myristate (MYR) and DZP on the FNZP photolabeling of these two
      major drug binding plasma proteins was examined. Photoincorporation was inhibited
      when HSA was photolabeled with [(3)H]FNZP in the presence of MYR but not in the
      presence of DZP. Conversely, DZP inhibited the photolabeling of [(3)H]FNZP to
      AGP. These results suggest that FNZP interacts with HSA at regions which are not
      located in the preformed binding pocket of subdomain III A.

PMID- 11295440
TI  - Synthesis, expression and characterisation of peptides comprised of perfect
      repeat motifs based on a wheat seed storage protein.
AB  - We have developed a novel method for constructing synthetic genes that encode a
      series of peptides comprising perfect repeat motifs based on a high molecular
      weight subunit (HMW glutenin subunit), a highly repetitive storage protein from
      wheat seed. A series of these genes of sequentially increasing size was produced,
      four of which (called R3, 4, 5, 6) were expressed in Escherichia coli. Activity
      of the synthetic genes in E. coli was confirmed by Northern blot analysis but SDS
      PAGE of crude protein extracts failed to show any expressed peptides when stained
      using Coomassie brilliant blue R250. However, Western blots probed with a HMW
      glutenin subunit-specific polyclonal antibody showed the presence of the R6
      peptide (M(r) 22005) in the crude cell extracts and both this and the R3 peptide
      (M(r) 12005) were subsequently purified by extraction with hot aqueous ethanol
      followed by precipitation with acetone and separated by RP-HPLC. The R4 and R5
      peptides were not purified. The purified R3 and R6 peptides absorbed Coomassie
      brilliant blue R250 or other protein stains only weakly and this was considered
      to account for their failure to be revealed by staining of separations of the
      crude protein extracts. Circular dichroism spectroscopy showed that both peptides
      had similar beta-turn rich structures similar to the repetitive sequences present
      in the whole HMW glutenin subunits. We conclude that expression of perfect repeat
      peptides in E. coli is a suitable system for the study of structure-function
      relationships in wheat gluten proteins and other highly repetitive proteins.

PMID- 11295442
TI  - An EPR study of the peroxyl radicals induced by hydrogen peroxide in the haem
      proteins.
AB  - The reaction of hydrogen peroxide H(2)O(2) with horse heart metmyoglobin (HH
      metMb), sperm whale metmyoglobin (SW metMb) and human metHb (metHbA) was studied
      at pH 6-8 by low temperature (10 K) EPR spectroscopy with the emphasis on the
      peroxyl radicals formed during the reaction. The same type of peroxyl radical was
      found in both myoglobin systems, as was concluded from close similarities in the
      spectroscopic properties of the radicals and in their kinetic dependences. This
      is consistent with previous reports of the peroxyl radical being localised on the
      Trp14 of SW and HH myoglobins. There are two types of peroxyl radical found in
      the metHbA/H(2)O(2) system, one (ROO-I) having spectral parameters, kinetic and
      pH dependences similar to those of the peroxyl radical found in both myoglobin
      systems. The other peroxyl radical (ROO-II) found in metHbA treated with H(2)O(2)
      has slightly different, though distinguishable, spectral parameters and a
      significantly different kinetic dependence as compared to those of the peroxyl
      radical common for all three proteins studied (ROO-I). The concentration of ROO-I
      radical formed in the three proteins on addition of H(2)O(2) correlates with the
      effectiveness of incorporating molecular oxygen into styrene oxide reported
      before for these three proteins. It is shown that a different distance from Trp14
      to haem iron in the three proteins might be the structural basis for the
      different yield of the peroxyl radical and the different efficiency of
      incorporation of molecular oxygen into styrene. The site of the peroxyl radical
      found only in metHbA (ROO-II) is speculated to be the Trp37 residue of the beta
      subunit of HbA.

PMID- 11295441
TI  - Is aggregation of beta-amyloid peptides a mis-functioning of a current
      interaction process?
AB  - In a previous study, Hughes et al. [Proc. Natl. Acad. Sci. USA 93 (1996) 2065
      2070] demonstrated that the amyloid peptide is able to interact with itself in a
      two-hybrid system and that interaction is specific. They further supported that
      the method could be used to define the sequences that might be important in
      nucleation-dependent aggregation. The sequence of the amyloid peptide can be
      split into four clusters, two hydrophilic (1-16 and 22-28) and two hydrophobic
      (17-21 and 29-42). We designed by molecular modeling and tested by the two-hybrid
      approach, series of mutations spread all over the sequence and changing the
      distribution of hydrophobicity and/or the spatial hindrance. In the two-hybrid
      assay, interaction of native Abeta is reproduced. Screening of mutations
      demonstrates that the C-domain (residues 29-40 (42)), the median domain (residues
      17-22) and the N-domain (1-16) are all crucial for interaction. This demonstrates
      that almost all fragments of the amyloid peptide but a loop (residues 23-28) and
      the C-term amino acid are important for the native interaction. We support that
      the folded three-dimensional (3D) structure is the Abeta-Abeta interacting
      species, that the whole sequence is involved in that 3D fold which has a low
      secondary structure propensity and a high susceptibility to mutations and thus
      should have a low stability. The native fold of Abeta could be stabilized in
      Abeta-Abeta complexes which could in other circumstances facilitate the
      nucleation event of aggregation that leads to the formation of stable senile
      plaques.

PMID- 11295443
TI  - Enzyme-catalyzed and enzyme-triggered pathways in dioxygenation of 1
      monolinoleoyl-rac-glycerol by potato tuber lipoxygenase.
AB  - It was shown for the first time that potato tuber lipoxygenase (ptLOX) catalyzed
      the aerobic oxidation of 1-monolinoleoyl-rac-glycerol (mLG) in a mixed micellar
      reaction solution with the non-ionic detergent monododecyl ether of
      decaoxyethylene glycol. No hydrolysis of mLG occurred during the reaction. The
      four major reaction products obtained at 23 degrees C were identified as 1-[9
      hydroperoxy-10E,12Z-octadecadienoyl]-rac-glycerol (9-(E,Z)HPODE-GE, 41%), 1-[13
      hydroperoxy-9Z,11E-octadecadienoyl]-rac-glycerol (13-(Z,E)-HPODE-GE, 17%), and
      their all-trans isomers ( approximately 21% each). The molar fraction of all
      trans isomers depended on the temperature of the reaction solution; it was found
      that at 0 degrees C their molar fractions were approximately 15.5% each, while 9
      (E,Z)HPODE-GE and 13-(Z,E)-HPODE-GE gave 42% and 27%, respectively, of the
      overall product. A free radical scavenger, 4-hydroxy-TEMPO, dramatically
      increased the molar fraction of 9-(E,Z)HPODE-GE, yielding 83% at 23 degrees C, at
      the expense of all other products. Chiral HPLC of 9-(E,Z)HPODE-GE formed in the
      presence of 4-hydroxy-TEMPO revealed that it was composed of approximately 94% S
      and approximately 6% (R) isomers. This assures largely a uniform orientation of
      mLG molecules in the ptLOX active center, with their methyl end most likely
      deepened into the protein globule. The second major product, 13-(Z,E)-HPODE-GE,
      which yielded approximately 9% of the total product formed in the presence of 4
      hydroxy-TEMPO, was racemic, and so were the all-trans isomers. Therefore, the
      last three cannot be considered the true products of the enzyme reaction, which
      is known to be stereospecific. It appears that they were formed as a result of
      (i) leakage of the pentadienyl radicals from the ptLOX active center and their
      subsequent non-enzymatic dioxygenation, and/or (ii) leakage of the peroxyl
      radicals leading to a free radical chain reaction affording all positional,
      geometrical and stereoisomers of the products. This reaction resembles ptLOX
      oxidation of another non-ionizable substrate, linoleyl alcohol [I.A. Butovich,
      S.M. Luk'yanova, C.C. Reddy, Arch. Biochem. Biophys. 378 (2000) 65-77], and
      differed substantially from oxidation of ionizable linoleic acid. Consequently,
      formation of large amounts of the non-specific oxidation products might be
      considered a universal characteristic of ptLOX oxidation of non-ionizable
      compounds.

PMID- 11295444
TI  - Characterization of a recombinant chimeric plasminogen activator with enhanced
      fibrin binding.
AB  - A recombinant chimeric plasminogen activator (GHRP-scu-PA-32K), consisting of the
      tetrapeptide Gly-His-Arg-Pro fused to the N-terminus of the low-molecular single
      chain urokinase-type plasminogen activator (Leu144-Leu411), was produced by
      expression in CHO cells. The stable expression cell line was selected for large
      scale expression. The product was purified by antibody-Sepharose affinity
      chromatography with a recovery of 67%. The apparent molecular weight of purified
      GHRP-scu-PA-32K was 33 kDa according to SDS-PAGE. Its specific activity was
      150000 IU/mg protein according to fibrin plate determination. The conversion of
      single-chain to two-chain molecules mediated by plasmin was comparable for GHRP
      scu-PA-32K (K(m)=4.9 microM, k(2)=0.35 s(-1)) and scu-PA-32K. The activation of
      plasminogen by GHRP-scu-PA-32K (K(m)=1.02 microM, k(2)=0.0028 s(-1)) was also
      similar to that of scu-PA-32K. The fibrin binding of GHRP-scu-PA-32K was 2.5
      times higher than that of scu-PA-32K at a fibrin concentration of 3.2 mg/ml. In
      contrast to scu-PA-32K in vitro 125I-fibrin-labeled plasma clot lysis, GHRP-scu
      PA had a higher thrombolytic potency, whereas it depleted less fibrinogen in
      plasma. These results show that GHRP-scu-PA-32K as expected is a potential
      thrombolytic agent.

PMID- 11295445
TI  - Activation of enzymes for nonaqueous biocatalysis by denaturing concentrations of
      urea.
AB  - Urea is one of the most commonly used denaturants of proteins. However, herein we
      report that enzymes lyophilized from denaturing concentrations of aqueous urea
      exhibited much higher activity in organic solvents than their native
      counterparts. Thus, instead of causing deactivation, urea effected unexpected
      activation of enzymes suspended in organic media. Activation of subtilisin
      Carlsberg (SC) in the organic solvents (hexane, tetrahydrofuran, and acetone)
      increased with increasing urea concentrations up to 8 M. Active-site titration
      results and activity assays indicated the presence of partially unfolded but
      catalytically active SC in 8 M urea; however, the urea-modified enzyme retained
      high enantioselectivity and was ca. 80 times more active than the native enzyme
      in anhydrous hexane. Likewise, the activity of horseradish peroxidase (HRP)
      lyophilized from 8 M urea was ca. 56 times and 350 times higher in 97% acetone
      and water-saturated hexane, respectively, than the activity of HRP lyophilized
      from aqueous buffer. Compared with the native enzyme, the partially unfolded
      enzyme may have a more pliant and less rigid conformation in organic solvents,
      thus enabling it to retain higher catalytic activity. However, no substantial
      activation was observed for alpha-chymotrypsin lyophilized from urea solutions in
      which the enzyme retained some activity, illustrating that the activation effect
      is not completely general.

PMID- 11295446
TI  - Influence of ligand binding to human cytochrome P-450 1A2: conformational
      activation and stabilization by alpha-naphthoflavone.
AB  - Human cytochrome P-450 (P-450) 1A2 expressed in Escherichia coli is readily
      converted into non-native cytochrome P-420 (P-420) in the presence of detergents.
      alpha-Naphthoflavone (ANF) has been used to prevent P-450 1A2 inactivation to P
      420 during purification. However, the mechanism by which ANF modulates P-450 1A2
      is not clearly understood. We observed that recombinant human P-450 1A2 prepared
      in the absence of ANF has an approx. 5 times higher maximum catalytic activity in
      the O-deethylation of 7-ethoxycoumarin than that in the presence of ANF, with the
      same K(m) values. The results revealed that the enzyme purified with ANF is not
      catalytically fully active, indicating that ANF tightly binds to the enzyme, only
      to be dissociated by heat denaturation. Furthermore, the inactive P-420 form of
      the enzyme could be reconverted to P-450 by ANF in high concentrations of
      detergents. The reconversion was concentration-dependent, confirming ANF-induced
      regeneration of active P-450 1A2. The reconversion coincided with the
      conformational change of the enzyme including increased alpha-helix content. The
      conformation of P-450 1A2 was also stabilized by ANF, resulting in an approx. 5
      degrees C increase in thermal stability.

PMID- 11295448
TI  - A leucine zipper protein of mitochondrial origin.
AB  - Sequence-specific DNA-binding proteins are characterised by short coiled-coil
      structural domains classified as zinc finger/RING finger, leucine zipper (L-Zip)
      or helix-loop-helix (HLH) motifs. The L-Zip proteins are defined by a pattern of
      at least four leucine (L) residues repeated every seventh amino acid that
      mediates protein dimerisation through the formation of parallel alpha-helical
      dimers. Usually the zipper is incorporated into a helix-loop-helix conformation
      called the basic helix-loop-helix-leucine zipper (bHLH/Zip). To date, all of the
      several hundred proteins reported as containing the L-Zip and/or bHLH/Zip motifs
      are nuclear-encoded. No leucine zipper polypeptide has, hitherto, been reported
      as mitochondrial in origin. Here we report such a polypeptide, the nicotinamide
      dehydrogenase subunit 4L (nad4L). We first identified this in human blood flukes
      of the genus Schistosoma (phylum Platyhelminthes; class Trematoda) but show that
      this is a common feature in other eucaryotes as well. Therefore, in addition to
      their well recognised role in oxidative phosphorylation, nad4L proteins may be
      pivotally involved in a range of other biological processes such as transcription
      and/or replication activation or as signal transmitters in communication with the
      nucleus and other cellular organelles. This may indicate a link between
      transcription regulation and respiration in mitochondria. We have also identified
      L-Zip-like motifs in nuoK, the procaryotic equivalent of the nad4L mitochondrial
      protein.

PMID- 11295447
TI  - S-Transnitrosylation of albumin in human plasma and blood in vitro and in vivo in
      the rat.
AB  - S-Nitrosoalbumin (SNOALB) is the most abundant physiological circulating nitric
      oxide (NO) carrier regulating NO-dependent biological actions in humans. The
      mechanisms of its formation and biological actions are still incompletely
      understood. Nitrosation by authentic NO and S-transnitrosylation of the single
      sulfhydryl group located at Cys-34 of human albumin by the physiological S
      nitroso compounds S-nitrosocysteine (SNOC) and S-nitrosoglutathione (GSNO) are
      two possible mechanisms. On a quantitative basis, we investigated by gas
      chromatography-mass spectrometry the contribution of these two mechanisms to
      SNOALB formation in human plasma and blood in vitro. GSNO and SNOC (0-100 microM)
      rapidly and efficiently (recovery=35%) S-transnitrosylated albumin to form
      SNOALB. NO (100 microM) S-nitrosated albumin to SNOALB at a considerably lower
      extent (recovery=5%). The putative NO-donating drugs glyceryl trinitrate and
      sodium nitroprusside (each 100 microM) failed completely in S-nitrosating
      albumin. Bubbling NO into human plasma and blood resulted in formation of SNOALB
      that inhibited ADP-induced platelet aggregation. Infusion of GS(15)NO in the rat
      resulted in formation of S(15)NOALB, [(15)N]nitrate and [(15)N]nitrite. Our
      results suggest that S-transnitrosylation of albumin by SNOC and GSNO could be a
      more favored mechanism for the formation of SNOALB in the circulation in vivo
      than S-nitrosation of albumin by NO itself.

PMID- 11295449
TI  - Grazing of protozoa and its effect on populations of aquatic bacteria.
AB  - Predation by bacterivorous protists in aquatic habitats can influence the
      morphological structure, taxonomic composition and physiological status of
      bacterial communities. The protistan grazing can result in bacterial responses at
      the community and the species level. At the community level, grazing-induced
      morphological shifts have been observed, which were directed towards either
      larger or smaller bacterial sizes or in both directions. Morphological changes
      have been accompanied by changes in taxonomic community structure and bacterial
      activity. Responses at the species level vary from species to species. Some taxa
      have shown a pronounced morphological plasticity and demonstrated complete or
      partial shifts in size distribution to larger growth forms (filaments,
      microcolonies). However, other taxa with weak plasticity have shown no ability to
      reduce grazing mortality through changes in size. The impact of protistan grazing
      on bacterial communities is based on the complex interplay of several parameters.
      These include grazing selectivity (by size and other features), differences in
      sensitivity of bacterial species to grazing, differences in responses of single
      bacterial populations to grazing (size and physiology), as well as the direct and
      indirect influence of grazing on bacterial growth conditions (substrate supply)
      and bacterial competition (elimination of competitors).

PMID- 11295450
TI  - Phylogenetic characterization of the blue filamentous bacterial community from an
      Icelandic geothermal spring.
AB  - Molecular phylogenetic analysis of a blue filamentous community from an alkaline
      thermal spring (79-83 degrees C) in Iceland revealed that the blue filaments were
      affiliated with the Aquificales. The dominant sequence type, pIce1, was most
      closely related to a sequence (SRI-48) found in a white filamentous community
      from a separate Icelandic thermal spring and the pink filaments (EM17) from
      Yellowstone National Park. Fluorescent in situ hybridization with clone-specific
      oligonucleotide probes showed that the sample analyzed was essentially a
      monoculture of a single phylotype.

PMID- 11295451
TI  - 16S rDNA fingerprinting of rhizosphere bacterial communities associated with
      healthy and Phytophthora infected avocado roots.
AB  - Molecular techniques employing 16S rDNA profiles generated by PCR-DGGE were used
      to detect changes in bacterial community structures of the rhizosphere of avocado
      trees during infection by Phytophthora cinnamomi and during repeated
      bioaugmentation with a disease suppressive fluorescent pseudomonad. When the 16S
      rDNA profiles were analyzed by multivariate analysis procedures, distinct
      microbial communities were shown to occur on healthy and infected roots.
      Bacterial communities from healthy roots were represented by simple DNA banding
      profiles, suggestive of colonization by a few predominant species, and were
      approximately 80% similar in structure. In contrast, roots that were infected
      with Phytophthora, but which did not yet show visible symptoms of disease, were
      colonized by much more variable bacterial communities that had significantly
      different community structures from those of healthy roots. Root samples from
      trees receiving repeated applications of the disease suppressive bacterium
      Pseudomonas fluorescens st. 513 were free of Phytophthora infection, and had
      bacterial community structures that were similar to those of nontreated healthy
      roots. Sequence analysis of clones generated from four predominant bands cut from
      the DGGE gels revealed the presence of pseudomonads, as well as several
      previously unidentified bacteria. Differentiation of 16S rDNA profiles for
      healthy and infected roots suggests that rhizosphere bacterial community
      structure may serve as an integrative indicator of changes in chemical and
      biological conditions in the plant rhizosphere during the infection process.

PMID- 11295452
TI  - Biological activity and colonization pattern of the bioluminescence-labeled plant
      growth-promoting bacterium Kluyvera ascorbata SUD165/26.
AB  - Kluyvera ascorbata SUD165/26 is a spontaneous siderophore-overproducing mutant of
      K. ascorbata SUD165, which was previously isolated from nickel-contaminated soil
      and shown to significantly enhance plant growth in soil contaminated with high
      levels of heavy metals. To develop a better understanding of the functioning of
      K. ascorbata SUD165/26 in the environment, and to trace its distribution in the
      rhizosphere, isolates of this bacterium were labeled with either green
      fluorescent protein or luciferase. When the plant growth-promoting activities of
      the labeled strains were assayed and compared with the activities of the
      unlabeled strain, none of the monitored parameters had changed to any significant
      extent. When the spatial colonization patterns of the labeled bacteria on canola
      roots were determined after seed application, it was observed that the bacterium
      was tightly attached to the surface of both roots and seeds, and formed
      aggregates. The majority of the bacterial population inhabited the upper two
      thirds of the roots, with no bacteria detected around the root tips.

PMID- 11295453
TI  - Molecular characterization of sulfate-reducing bacteria in anaerobic hydrocarbon
      degrading consortia and pure cultures using the dissimilatory sulfite reductase
      (dsrAB) genes.
AB  - The characterization of sulfate-reducing bacteria (SRBs) is presented using the
      dissimilatory sulfite reductase (dsrAB) gene from various samples capable of
      mineralizing petroleum components. These samples include several novel,
      sulfidogenic pure cultures which degrade alkanes, toluene, and tribromophenol.
      Additionally, we have sulfidogenic consortia which re-mineralize benzene,
      naphthalene, 2-methylnaphthalene, and phenanthrene as a sole carbon source. In
      this study, 22 new dsrAB genes were cloned and sequenced. The dsrAB genes from
      our pollutant-degrading cultures or consortia were distributed among known SRBs
      and previously described dsrAB environmental clones, suggesting that many
      biodegradative SRBs are phylogenetically distinct and geographically wide spread.
      Specifically, the same dsrAB gene was discovered in independently established
      consortia capable of benzene, phenanthrene, and methylnaphthalene degradation,
      indicating that this particular SRB may be a key player in anaerobic degradation
      of hydrocarbons in the environment.

PMID- 11295454
TI  - Solubilisation and colonisation of wood ash by ectomycorrhizal fungi isolated
      from a wood ash fertilised spruce forest.
AB  - In Sweden application of granulated wood ash has been suggested as a method to
      supplement nutrient loss resulting from harvesting of forest residues for
      bioenergy production. Mycelia of two ectomycorrhizal fungi Piloderma sp. 1 and Ha
      96-3, were commonly found to colonise ash granules in a wood ash fertilised
      spruce forest. Thirty-eight fungal isolates were selected from 10 taxa to
      investigate the possible role of different ectomycorrhizal fungi in nutrient
      mobilisation from ash. The taxa were Cenococcum geophilum Fr., Piloderma croceum
      Erikss. and Hjortst., Piloderma sp. 1, Thelephora terrestris (Ehrenb.) Fr.,
      Tylospora fibrillosa Donk, and five unidentified species, all originating from a
      wood ash fertilised spruce forest. The isolates were tested for their ability to
      solubilise tricalcium phosphate (TCP) or hardened wood ash (HWA) in vitro. Ha-96
      3, P. croceum and Piloderma sp. 1 were the only taxa which solubilised TCP.
      Abundant calcium oxalate crystals were formed in TCP and HWA plates with
      Piloderma sp. 1. Ha-96-3 and two isolates of P. croceum produced intermediate
      amounts of crystals. Ha-96-1 and T. fibrillosa produced low amounts of crystal
      but no crystal formation was observed by any of the other isolates. Piloderma sp.
      1 from HWA plates had significantly higher concentrations of P, compared to P.
      croceum or Ha-96-3. Piloderma sp. 1 and P. croceum were further tested for their
      ability to colonise wood ash in microcosms containing intact mycorrhizal
      associations. After 7 months Piloderma sp. 1 colonised ash amended patches with a
      dense, mat like mycelium, whereas P. croceum mycelia avoided the ash patches.
      Possible differences between these fungi in patterns of carbon allocation were
      investigated by labelling seedlings with 14CO(2). Piloderma sp. 1 mycelia
      allocated significantly more 14C to ash patches than P. croceum. P. croceum
      allocated relatively more 14C to control patches than to the ash patches. The
      possible role of ectomycorrhizal fungi in mobilisation of nutrients from wood ash
      is discussed.

PMID- 11295455
TI  - Is interspecies hydrogen transfer needed for toluene degradation under sulfate
      reducing conditions?
AB  - Sediments from a hydrocarbon-contaminated aquifer, where periodic shifts between
      sulfate reduction and methanogenesis occurred, were examined to determine whether
      the degradation of toluene under sulfate-reducing conditions depended on
      interspecies hydrogen transfer. Toluene degradation under sulfate-reducing
      conditions was inhibited by the addition of 5 mM sodium molybdate, but the
      activity was not restored upon the addition of an actively growing, hydrogen
      using methanogen. Toluene degradation was not inhibited in microcosms where
      hydrogen levels were maintained at a level theoretically sufficient to inhibit
      toluene degradation if the process proceeded via interspecies hydrogen transfer.
      Finally, the addition of carbon monoxide, a potent inhibitor of hydrogenase
      activity, inhibited hydrogen but not toluene consumption in sulfate-reducing
      microcosms. These results suggest that toluene is degraded directly by sulfate
      reducing bacteria without the involvement of interspecies hydrogen transfer. The
      sequence of experiments used to reach this conclusion could be applied to
      determine the role of interspecies hydrogen transfer in the degradation of a
      variety of compounds in different environments or under different terminal
      electron-accepting conditions.

PMID- 11295456
TI  - Are the actively respiring cells (CTC+) those responsible for bacterial
      production in aquatic environments?
AB  - The 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) staining method is commonly
      and increasingly used to detect and to enumerate actively respiring cells (CTC+
      cells) in aquatic systems. However, this method remains controversial since some
      authors promote this technique while others pointed out several drawbacks of the
      method. Using flow cytometry (FCM), we showed that CTC staining kinetics vary
      greatly from one sample to another. Therefore, there is no universal staining
      protocol that can be applied to aquatic bacterial communities. Furthermore, using
      (3)H-leucine incorporation, it was shown that the CTC dye has a rapid toxic
      effect on bacterial cells by inhibiting protein synthesis, a key physiological
      function. The coupling of radioactive labelling with cell sorting by FCM
      suggested that CTC+ cells contribute to less than 60% of the whole bacterial
      activity determined at the community level. From these results, it is clearly
      demonstrated that the CTC method is not valid to detect active bacteria, i.e.
      cells responsible for bacterial production.

PMID- 11295457
TI  - Synergism between Phyllobacterium sp. (N(2)-fixer) and Bacillus licheniformis (P
      solubilizer), both from a semiarid mangrove rhizosphere.
AB  - Mangrove seedlings were treated with a mixture of two bacterial species, the slow
      growing, N(2)-fixing bacterium Phyllobacterium sp. and the fast-growing,
      phosphate-solubilizing bacterium Bacillus licheniformis, both isolated from the
      rhizosphere from black, white, and red mangroves of a semiarid zone. Nitrogen
      fixation and phosphate solubilization increased when the mixture was used
      compared to the effects observed when adding individual cultures, notwithstanding
      that there was no increase in bacterial multiplication under these conditions.
      Inoculation of black mangrove seedlings in artificial seawater showed the mixture
      performed somewhat better than inoculation of the individual bacterium; more
      leaves were developed and higher levels of (15)N were incorporated into the
      leaves, although the total nitrogen level decreased. This study demonstrates that
      interactions between individual components of the rhizosphere of mangroves should
      be considered when evaluating these bacteria as plant growth promoters.

PMID- 11295458
TI  - Development of primers for amplifying genes encoding CprA- and PceA-like
      reductive dehalogenases in anaerobic microbial consortia, dechlorinating
      trichlorobenzene and 1,2-dichloropropane.
AB  - Gene sequence alignments of the reductive dehalogenases PceA (Dehalospirillum
      multivorans) and CprA (Desulfitobacterium dehalogenans) were used to develop
      specific PCR primers binding to conserved regions of these sequences. These
      primers enabled us to amplify and subsequently sequence cprA-like gene fragments
      from the chlororespiring species Dehalobacter restrictus, Desulfitobacterium sp.
      strain PCE1, and D. hafniense. No specific amplicons were obtained from the
      chlororespiring species D. frappieri, D. chlororespirans, and Desulfomonile
      tiedjei. Furthermore, we were able to amplify and sequence cprA/pceA-like gene
      fragments from both trichlorobenzene (TCB)- and 1,2-dichloropropane (DCP)
      dechlorinating microbial consortia using the novel primers. Subsequent sequence
      analysis of the fragments obtained from the microbial consortia revealed a group
      of four clusters (I-IV). Of these, clusters I and II showed the highest
      similarities to the cprA-like gene of Dehalobacter restrictus (79.0 and 96.2%,
      respectively). Cluster III comprised cprA-like sequences found in both the TCB-
      and the DCP-dechlorinating consortia, whereas sequences of cluster IV were most
      similar to the pceA gene of Dehalospirillum multivorans (97.8%). Our detection of
      genes encoding reductive dehalogenases, the key enzymes of chlororespiration,
      supports the hypothesis that reductive dechlorination of TCB and DCP occurs via a
      respiratory pathway.

PMID- 11295459
TI  - Gene transfer and plasmid instability within pilot-scale sewage filter beds and
      the invertebrates that live in them.
AB  - The environmental plasmid pQKH6 was transferred conjugatively between strains of
      Pseudomonas putida at mean frequencies of up to 8.4x10(-4) within pilot-scale
      sewage filter beds. This frequency was 10-fold higher than that reported
      previously for this environment and was probably due to seasonal temperature
      changes. Many (45%) of the plasmids isolated subsequently from the filter beds
      had restriction fragment length polymorphism (RFLP) profiles that differed from
      that expected for pQKH6. RFLP analysis revealed structural rearrangements
      occurring within a particularly restriction-site-rich region of the plasmid.
      Although no evidence was obtained showing the indigenous invertebrate populations
      within the filter beds to influence the rate of gene transfer, pQKH6 was
      transferred with frequencies of up to 1.6x10(-2) within the guts of the filter
      bed-dwelling Sylvicola fenestralis larvae during laboratory experiments. This
      transfer was strongly influenced by donor to recipient ratios. Laboratory
      experiments also showed that Serratia fonticola survived better within
      invertebrate guts than P. putida. This evidence, along with experiments showing
      that S. fonticola could participate in pQKH6 transfer within filter-bed biofilm,
      identify this bacterium as a better model than P. putida for examining the effect
      of invertebrates on gene transfer.

PMID- 11295460
TI  - Microbial diversity in hot synthetic compost as revealed by PCR-amplified rRNA
      sequences from cultivated isolates and extracted DNA.
AB  - High-temperature (>/=60 degrees C) synthetic food waste compost was examined by
      cultivation-dependent and -independent methods to determine predominant microbial
      populations. Fluorescent direct counts totaled 6.4 (+/-2.5)x10(10) cells gdw(-1)
      in a freeze-dried 74 degrees C compost sample, while plate counts for
      thermophilic heterotrophic aerobes averaged 2.6 (+/-1.0)x10(8) CFU gdw(-1). A pre
      lysis cell fractionation method was developed to obtain community DNA and a suite
      of 16S and 18S rDNA-targeted PCR primers was used to examine the presence of
      Bacteria, Archaea and fungi. Bacterial 16S rDNA, including a domain-specific 1500
      bp fragment and a 300-bp fragment specific for Actinobacteria, was amplified by
      PCR from all compost samples tested. Archaeal rDNA was not amplified in any
      sample. Fungal 18S rDNA was only amplified from a separate dairy manure compost
      that reached a peak temperature of 50 degrees C. Amplified rDNA restriction
      analysis (ARDRA) was used to screen isolated thermophilic bacteria and a clone
      library of full-length rDNA fragments. ARDRA screening revealed 14 unique
      patterns among 63 isolates, with one pattern accounting for 31 of the isolates.
      In the clone library, 52 unique patterns were detected among 70 clones,
      indicating high diversity of uncultivated bacteria in hot compost. Phylogenetic
      analysis revealed that the two most abundant isolates belonged in the genera
      Aneurinibacillus and Brevibacillus, which are not commonly associated with hot
      compost. With the exception of one Lactobacillus-type sequence, the clone library
      contained only sequences that clustered within the genus Bacillus. None of the
      isolates or cloned sequences could be assigned to the group of obligate
      thermophilic Bacillus spp. represented by B. stearothermophilus, commonly
      believed to dominate high-temperature compost. Amplified partial fragments from
      Actinobacteria, spanning the V3 variable region (Neefs et al. (1990) Nucleic
      Acids Res. 18, 2237-2242), included sequences related to the genera
      Saccharomonospora, Gordonia, Rhodococcus and Corynebacterium, although none of
      these organisms were detected among the isolates or full-length cloned rDNA
      sequences. All of the thermophilic isolates and sequenced rDNA fragments examined
      in this study were from Gram-positive organisms.

PMID- 11295461
TI  - The limits to genomic predictions: role of sigma(N) in environmental stress
      survival of Pseudomonas putida.
AB  - Based on genomic data and on the phenotypes of an FlhF mutant of Pseudomonas
      putida, the alternative sigma factor sigma(N) (sigma(54)) has been proposed to
      play a key role in survival to various nutritional and environmental stresses in
      this bacterium. Quite in contrast, we show that unlike sigma(S) (sigma(38)) the
      loss of sigma(N) does not impair to any significant extent the ability of P.
      putida to survive long-term starvation. rpoN mutants (lacking sigma(N)) are
      indistinguishable from the wild-type with respect to solvent tolerance,
      resistance to heat shock or sensitivity to hydrogen peroxide. These data suggest
      that while sigma(N) is a key component of expression of alternative
      biodegradative pathways for unusual carbon sources (i.e. m-xylene or
      dimethylphenols), its loss does not compromise bacterial endurance to gross types
      of environmental stress. Moreover, these results point out the limitations, if
      not the deception, of genomic predictions when confronted with experimental data.

PMID- 11295462
TI  - Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65
      peptides with sequence homology to Coxsackie or proinsulin peptides do not
      crossreact with homologous counterpart.
AB  - Type 1 diabetes mellitus is a T-cell mediated autoimmune disease in which the
      insulin-producing pancreatic beta cells are selectively destroyed. Molecular
      mimicry and T-cell crossreactivity to beta-cell autoantigens and environmental
      agents with sequence similarities have been a proposed mechanism underlying the
      pathogenesis of type 1 diabetes, but actual crossreactivity has not yet been
      demonstrated. We isolated and investigated T cells reactive to GAD65 peptides and
      homologous peptides of the Coxsackie virus protein P2C and proinsulin from recent
      onset type 1 diabetes patients, and tested their fine specificity and cytokine
      production profile. Six T-cell lines specific for GAD65 peptides (amino acids 491
      530) with homology to proinsulin (B20-C14) were isolated from six newly diagnosed
      patients with type 1 diabetes, but none of the stable T-cell lines crossreacted
      to the homologous proinsulin peptides. Similarly, none of four T-cell lines
      reactive to GAD65 peptides (amino acids 247-280) with sequence homology to
      Coxsackie P2C (amino acids 30-50) crossreacted to the homologous viral peptide.
      Two T-cell lines corecognized a GAD65 peptide and a Coxsackie P2C peptide.
      However, the antigen-specific T-cell clones from these T-cell lines were reacting
      either with the GAD65 peptide or the Coxsackie P2C peptide using different
      restriction elements without crossreacting to the homologous peptide. Our data
      demonstrate that homologous peptides previously proposed to serve as targets for
      crossreactivity indeed are immunogenic. Yet, T-cell clones did not crossreact
      with linear sequence homologies, despite strong T-cell responses to individual
      peptides.

PMID- 11295463
TI  - Evidence that Fas-induced apoptosis leads to S phase arrest.
AB  - Cell death by apoptosis is an efficient mechanism of eliminating unwanted or
      aberrant cells. Triggering of Fas, a member of the tumor necrosis factor (TNF)
      receptor superfamily, by anti-Fas antibodies or by the Fas ligand (FasL), has
      been shown to cause cell death by apoptosis. A recent study from our laboratory
      has demonstrated that Fas crosslinking leads to the dephosphorylation of the
      tumor suppressor retinoblastoma protein (Rb) and that this dephosphorylation is
      inhibited by calyculin A, a serine/threonine phosphatase inhibitor. In this
      investigation, we compared the effect of Fas crosslinking by CH11, an anti-Fas
      mAb, with two cyclin-dependent kinase (CDK) inhibitors, a peptide that
      specifically inhibits CDK2 (cdk2 inh) and roscovitine, which inhibits CDK2, CDC2,
      and CDK5. We illustrate that roscovitine induced DNA fragmentation, whereas cdk2
      inh did not. In contrast to Fas-induced apoptosis, roscovitine-induced apoptosis
      was resistant to calyculin A. Both cdk2 inh and roscovitine induced cleavage of
      poly (ADP-ribose) polymerase (PARP) within 2 h. Roscovitine, however, led to the
      degradation of Rb, whereas cdk2 inh did not. Furthermore, both CH11 and
      roscovitine caused cell cycle arrest in S phase. In contrast, cdk2 inh did not
      have any effect on Jurkat cell cycle progression. Taken together, our results
      strongly suggest that the maintenance of Rb in its hyperphosphorylated form
      during S phase may be necessary for cell survival and that Rb dephosphorylation
      during S phase may constitute a crucial step in Fas-induced apoptosis.

PMID- 11295464
TI  - Activation of c-Jun N-terminal kinase in the absence of NFkappaB function prior
      to induction of NK cell death triggered by a combination of anti-class I and anti
      CD16 antibodies.
AB  - Addition of antibodies to major histocompatibility complex class I (MHC class I)
      and F(c) gamma RIII (CD16) antigens resulted in the synergistic augmentation of
      natural killer (NK) cell death, and the loss of NK cell cytotoxic function. The
      binding of anti-CD16 and anti-class I antibodies to the same population of NK
      cells is required for the synergistic augmentation of NK cell death. Moreover,
      the addition of antibodies to leukocyte function antigen-1 (LFA-1), which
      significantly inhibited the phorbol 12-myristate 13-acetate (PMA) and ionomycin
      mediated NK cell death, had no effect on NK cell death mediated by anti-CD16 and
      anti-class I antibodies. The increase in NK cell death was associated with an
      increase in tumor necrosis factor-alpha (TNF-alpha) secretion, and concomitant
      inhibition of nuclear factor kappa B (NFkappaB) activation and the induction of c
      jun N-terminal kinase (JNK) activity in NK cells treated with the combination of
      anti-class I and anti-CD16 antibodies. Furthermore, the inhibition of NFkappaB
      activation in anti-CD16 and anti-class I antibody treated NK cells was paralleled
      with a significant increase in inhibitor of kappa B (IkappaB) protein expression.
      Overexpression of IkappaB super-repressor in YT, a NK cell line, caused
      significant up-regulation of TNF-alpha, PMA and ionomycin and Fusobacterium
      nucleatum mediated NK cell death. Overall, our studies suggest an important
      regulatory role for NFkappaB and JNK activities in MHC class I mediated NK cell
      death.

PMID- 11295465
TI  - Human squamous cell carcinomas of the head and neck chemoattract immune
      suppressive CD34(+) progenitor cells.
AB  - CD34(+) progenitor cells have previously been shown to be mobilized in patients
      with squamous cell carcinoma of the head and neck (HNSCC). The present study
      showed that these CD34(+) cells inhibit the capacity of intratumoral lymphoid
      cells to become activated in response to stimulation through the TCR/CD3 complex.
      The mechanisms that could lead to the accumulation of CD34(+) cells within the
      tumor tissue were assessed. This was accomplished through in vitro studies that
      determined if HNSCC produce soluble factors that chemoattract CD34(+) cells. The
      migration of cord blood CD34(+) cells, which were used as a readily available
      source of progenitor cells, was stimulated by products derived from HNSCC
      explants and primary HNSCC cultures. This stimulated migration was due to
      chemotaxis because it was dependent on an increasing gradient of HNSCC-derived
      products. CD34(+) cells that were isolated from the peripheral blood of HNSCC
      patients were similarly chemoattracted to the HNSCC-derived products. The
      majority of the chemotactic activity produced by HNSCC could be attributed to
      vascular endothelial cell growth factor (VEGF). These studies indicate that HNSCC
      can chemoattract immune inhibitory CD34(+) progenitor cells through their
      production of VEGF.

PMID- 11295466
TI  - Monitoring of intragraft and peripheral blood TIRC7 expression as a diagnostic
      tool for acute cardiac rejection in humans.
AB  - T-cell immune response cDNA 7 (TIRC7) is a recently described T-cell
      costimulatory molecule that exhibits a central role in T-cell activation in vitro
      and in vivo. The present study was undertaken to investigate association between
      intragraft and peripheral blood mononuclear cell (PBMC) TIRC7 mRNA levels and
      cardiac allograft rejection in humans. TIRC7 gene expression levels were
      determined by a quantitative-competitive reverse transcriptase-polymerase chain
      reaction (QC-RT-PCR) in endomyocardial biopsies and in PBMC from cardiac
      transplant recipients. Biopsies collected during rejection or up to 15 days
      before rejection showed heightened TIRC7 mRNA expression in comparison with
      biopsies without rejection. All prerejection and rejection biopsies showed TIRC7
      mRNA upregulation, while this was present in only 30% of the biopsies without
      rejection. Regarding TIRC7 mRNA in PBMC, transplant recipients showed lower
      levels than healthy individuals and, in contrast to the results obtained in
      biopsies, the levels were lower during rejection than in rejection-free periods.
      In summary, TIRC7 mRNA expression levels increase in biopsies and decrease in
      peripheral blood during acute cardiac rejection. We conclude that intragraft
      detection of TIRC7 transcripts is a useful tool not only for the diagnosis but
      also for the prediction of acute heart allograft rejection episodes.

PMID- 11295467
TI  - Altered antibody repertoires of plasma IgM and IgG toward nonself antigens in
      patients with warm autoimmune hemolytic anemia.
AB  - Warm autoimmune hemolytic anemia (WAIHA) is characterized by an accelerated
      extravascular clearance of red blood cells (RBC) mediated by RBC-bound IgG
      autoantibodies. We have recently demonstrated significantly altered self-reactive
      antibody (Ab) repertoires of plasma IgM in WAIHA patients. The natural IgM Ab
      repertoire in plasma is critical in modulating both autoimmune and alloimmune
      responses. In the present study, we investigated IgM and IgG Ab repertoires of
      WAIHA patients toward nonself antigens (Ag) using a quantitative immunoblotting
      technique, followed by multiparametric statistical analysis of the data. We
      demonstrate significantly altered Ab repertoires of IgM and IgG toward nonself Ag
      in WAIHA patients. The reactivity of plasma IgM of WAIHA patients was reduced
      compared to that of healthy individuals, independent of administering an
      immunosuppressive therapy. We observed that an increase in reactivity of plasma
      IgM during clinical remission of the disease was associated with the development
      of allo-Ab toward RBC-antigens during RBC transfusions. Taken together, the data
      indicate altered Ab repertoires of plasma IgM and IgG toward nonself Ag in WAIHA
      patients. A broadly reduced reactivity of plasma IgM toward nonself Ag might
      influence the adaptive immune response in WAIHA patients.

PMID- 11295468
TI  - Molecular profile of a human monoclonal antibody Fab fragment specific for
      Epstein-Barr virus gp350/220 antigen.
AB  - Experimental evidence indicates Epstein Barr virus (EBV) envelope glycoprotein
      gp350/220 elicits a potent virus neutralizing response in the infected human host
      that may play an important role in restricting viral pathogenesis. In this study,
      we report the molecular cloning in combinatorial phage display vectors, of the
      IgG1 repertoire of an individual naturally infected with EBV, and describe the
      recovery and characterization of a monoclonal antibody recognizing gp350/220. A
      detailed understanding of the human antibody response in EBV infection will
      identify antibodies of potential use in anti-viral prophylaxis and will advance
      the production of more effective vaccine candidates.

PMID- 11295469
TI  - Identification of four novel dinucleotide repeat polymorphisms in the IL-2 and IL
      2beta receptor genes.
AB  - Two polymorphic regions have been described within the IL-2 and IL-2 receptor
      beta genes comprising 15 and 8 alleles, respectively. Whether these polymorphisms
      have biologic importance is unknown, although they have been variably identified
      in associated with certain chronic disease states. We report here the detection
      of four new alleles designated IL-2 A* (122 bp), IL-2R-2 (169 bp), IL-2R 0 (165
      bp), and IL-2R 9 (147 bp) in patients with rheumatoid arthritis and normal
      controls from the Pacific Northwest. The number of alleles now recognized at
      these loci within the IL-2 and IL-2Rbeta genes increases to 16 and 12,
      respectively.

PMID- 11295470
TI  - Genetic susceptibility to multiple sclerosis: detection of polymorphic
      nucleotides and an intron in the 3' untranslated region of the major
      histocompatibility complex class II transactivator gene.
AB  - The master player in the transcriptional regulation of major histocompatibility
      (MHC) class II genes is a factor known as the MHC class II transactivator
      (CIITA). In this study we searched for polymorphisms in the 5' and 3' ends of the
      human CIITA gene to assess whether or not there is an association between alleles
      of this gene and multiple sclerosis (MS). Polymorphism screening based upon
      detection of single strand conformational changes (SSCP analysis) followed by
      sequencing revealed six single nucleotide variations, namely one in the promoter
      utilized by B cells and five in the 3' untranslated region (UTR) of the gene.
      Determination of alleles at these polymorphic sites was facilitated by treatment
      of amplified DNA fragments with a panel of appropriate restriction enzymes. The
      distributions of CIITA alleles did not differ between MS patients and control
      subjects (p > 0.05). After subgrouping of the patients into relapsing-remitting
      MS and primary progressive MS we found that the distribution of promoter alleles
      in the latter of these two patient groups differed from that of healthy control
      subjects (p = 0.04). There was no evidence of linkage disequilibrium between the
      polymorphic site in the B cell specific promoter and those in the 3' UTR. Based
      upon the polymorphic sites in the 3' UTR we identified two common CIITA
      haplotypes which were present at similar frequencies in patients and control
      subjects. Assuming that susceptibility to MS depends upon type of MHC class II
      molecule as well as the amounts of expressed class II molecules we tested for
      interaction between DR15 status and CIITA alleles. No such interaction was
      detected. Unexpectedly, we identified an intron in the 3' UTR of the human as
      well as the mouse CIITA gene. Due to the proximity of these introns to the
      termination codon in both the human and mouse CIITA gene, the mechanism for
      regulation of transcript stability known as nonsense-mediated decay is probably
      not involved in the posttranscriptional control of the expression of these genes.
      So far, the function and significance of the intron in the human and mouse CIITA
      genes are unknown.

PMID- 11295471
TI  - HLA diversity, differentiation, and haplotype evolution in Mesoamerican Natives.
AB  - Genetic variation of the Human Leukocyte Antigen region (HLA) in three Amerindian
      populations from the Southern Mexican state of Oaxaca, the Zapotec, Mixtec and
      the Mixe is examined. Individuals were typed using PCR-SSOP for four class II
      loci (DRB1, DQA1, DQB1, DPB1) and three class I loci (HLA-A, -B, and -C). Based
      on known HLA distributions, European admixture ranged from 1% to 10%. Individuals
      with European alleles were excluded from subsequent analysis. New alleles were
      revealed at each of the class I loci. In general, genotype frequencies were in
      Hardy-Weinberg equilibrium, although some deviations were detected. Allele
      frequency distributions at the DRB1, DQA1, DQB1 and HLA-A loci in all populations
      were more even than expected under neutrality, supporting a model of balancing
      selection at these loci. A history of directional selection for DPB1 in all three
      populations was indicated, as homozygosity values were significantly above
      expected values. Allele frequency distributions at HLA-B and HLA-C did not differ
      significantly from neutrality expectations. The data also provide evidence from
      linkage disequilibrium that strong haplotypic associations are present across the
      entire HLA region in each of the populations. Significant overall linkage
      disequilibrium exists between all pairs of loci typed in these populations,
      except those which include the DPB1 locus. These associations exist despite the
      fact that the recombination fraction between HLA-A, in the class I region, and
      DQB1, in the class II region, may exceed 0.02. One explanation is that selective
      pressures are maintaining the relationships between particular alleles at these
      loci in these populations. These relationships are maintained in general across
      the entire HLA region in the Oaxacan Amerindians, with the exception of DPB1.

PMID- 11295472
TI  - HLA alleles and IDDM in children in Hungary: a comparison with Finland.
AB  - It has been postulated that variation in the distribution of human leukocyte
      antigen (HLA)-encoded susceptibility alleles for insulin-dependent diabetes
      mellitus (IDDM) is the genetic basis for variation in the incidence of the
      disease between populations. The aim of this study was to characterize HLA
      encoded susceptibility to IDDM in Hungary and to identify whether HLA-DRB1/DQ
      encoded susceptibility could account for the five times lower incidence of
      disease in Hungary compared with Finland. The haplotypes DRB1*03-DQA1*05-DQB1*02
      (DRB1*03-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DRB1*04-DQ8) were significantly
      associated with disease in both populations. Three genotypes incorporating either
      or both of these haplotypes accounted for over 70% of the diabetic population in
      both races. The combined background frequency and the degree of risk as measured
      by odds ratios of these HLA-DRB1-DQ genotypes were not significantly different in
      the two countries. Comparison of the DRB1*0401-DQ8 haplotype between the two
      races suggested a role for HLA-B alleles in susceptibility. These data indicate
      that the susceptibility associated with high risk DRB1-DQ genotypes alone is
      insufficient to account for the fivefold variation in incidence of IDDM between
      Hungary and Finland. Other genetic and/or environmental influences must be
      involved.

PMID- 11295473
TI  - Effect of HLA class I or class II incompatibility in pediatric marrow
      transplantation from unrelated and related donors.
AB  - The degree of histoincompatibility that can be tolerated, and the relative
      importance of matching at individual HLA class I and class II locus in bone
      marrow transplantation (BMT) has not been established. We hypothesized that
      matching for HLA-DR may not be more important than matching for HLA-A or HLA-B in
      selection of a donor for successful BMT. We retrospectively analyzed the outcomes
      of 248 consecutive pediatric patients who received allogeneic BMT from related
      donors (RD, n = 119) or unrelated donors (URD, n = 129). HLA-A and HLA-B were
      serologically matched, and HLA-DRB1 were identical by DNA typing in 69% of donor
      recipient pairs. Most patients (89%) had hematologic malignancies; the rest had
      aplastic anemia or a congenital disorder. One HLA-A antigen mismatch was
      associated with a decrease in survival (p = 0.003) and a delay in granulocyte
      engraftment (p = 0.02) in recipients of RD marrow; as well as a decrease in
      survival (p = 0.02) and the development of severe acute graft-versus-host disease
      (GVHD) (p = 0.03) in recipients of URD marrow. One HLA-B antigen mismatch was
      associated with a decrease in the survival (p = 0.05) and the development of
      severe GVHD (p = 0.0007) in recipients of RD marrow. One HLA-DRB1 allele mismatch
      was associated only with a decrease in the survival (p = 0.0003) of recipients of
      RD marrow. Results of this study suggest that disparity in HLA-A and HLA-B
      antigens may not be better tolerated than disparity in HLA-DR allele in
      allogeneic BMT. Further studies are warranted to confirm our results.

PMID- 11295474
TI  - FcgammaRIII b and FcgammaRIIa polymorphism may affect the production of specific
      NA1 autoantibody and clinical course of autoimmune neutropenia of infancy.
AB  - We studied 18 children with autoimmune neutropenia (AIN) to evaluate whether
      there was a possible relationship between the specificity of granulocyte
      autoantibodies (anti-NA1,2) and the phenotype of the NA system. Direct
      granulocyte immunofluorescence test (D-GIFT) was positive in all patients, and
      indirect granulocyte immunofluorescence test (I-GIFT) was positive in 17 of these
      18 patients, respectively. Fourteen of 18 patients showed preferential binding to
      neutrophils from NA(1+2-) phenotyped donors. Immunoblotting with anti
      FcgammaRIIImAb showed that IgG prepared from 7 of 12 patients precipitated both
      FcgammaRIIIb from NA1 and NA2 neutrophil lysate, whereas the other 5 precipitated
      only NA1. Patients' IgG did not react with purified FcgammaRIIa. FcgammaRIIIb
      genotype were NA(1+2-) in 15 of 18 patients and NA(1+2+) in the other 3.
      FcgammaRIIa type of all patients were (H+R-). These distributions were
      significantly different from those of healthy Japanese blood donors (n = 608).
      The genotype of FcgammaRIIIb and FcgammaRIIa may affect the production of
      neutrophil specific auto-antibodies in AIN of infancy and influence its clinical
      course.

PMID- 11295475
TI  - HLA-B typing by reference strand mediated conformation analysis using a capillary
      based semiautomated genetic analyzer.
AB  - The application of reference strand conformation analysis (RSCA) to HLA-A typing
      using the ABI PRISM 310 capillary based genetic analyzer has recently been
      described. This study outlines the development and validation of capillary RSCA
      for HLA-B typing. Mobility values for 93 HLA-B alleles were defined following
      electrophoresis of known controls through the system. Three fluorescently
      labelled references, labelled with three different dyes can be electrophoresed
      simultaneously. The technique was validated by comparing results from 296 cord
      blood donors with those obtained using reverse SSO. Following capillary RSCA
      14.5% of samples required confirmatory typing, compared with a repeat rate of
      5.1% following reverse SSO. In samples where no other typing was necessary there
      was 100% correlation between the two methods. Capillary RSCA for HLA-B typing is
      quick, easy to implement, and with the introduction of new FLRs and gel matrices
      has the potential to evolve into a high resolution typing method.

PMID- 11295476
TI  - Nomenclature for factors of the HLA system, 2000.

PMID- 11295477
TI  - Skin sensitisation testing--new perspectives and recommendations.
AB  - Various methodological aspects of skin sensitisation testing have been explored,
      particularly in the context of animal welfare considerations and reliability and
      sensitivity of test methods. Recommendations are made for the conduct of current
      and proposed OECD skin sensitisation tests with respect to appropriate test
      configurations for the purposes of hazard identification and labelling, and the
      requirement for positive controls. Specifically, the following aspects of guinea
      pig sensitisation test methods have been addressed: (1) the number of test and
      control animals required; (2) the option of using joint positive controls between
      independent laboratories; (3) the choice of positive control chemicals; (4) the
      optimal conduct and interpretation of rechallenge; and (5) the requirement for
      pretreatment with sodium lauryl sulfate. In addition, the use of the murine local
      lymph node assay (LLNA) has been considered. A number of conclusions have been
      drawn and recommendations made as follows: In many instances, particularly with
      the conduct of the guinea pig maximisation test, it is acceptable to halve the
      number of test and control animals used. An optional scheme for the conduct of
      joint positive control studies within a co-ordinated group of laboratories is
      appropriate. Only one positive control chemical (alpha-hexyl cinnamic aldehyde)
      is necessary for the routine assessment of assay sensitivity. The proper conduct
      and interpretation of rechallenge can provide valuable information and
      confirmation of results in guinea pig sensitisation tests. Sodium lauryl sulfate
      should no longer be used as a pretreatment in the guinea pig maximisation test.
      The LLNA is a viable and complete alternative to traditional guinea pig test
      methods for the purposes of skin sensitisation hazard identification. These
      recommendations provide the opportunity for both animal welfare benefits and
      improved hazard identification.

PMID- 11295478
TI  - 14-Week toxicity and cell proliferation of methyleugenol administered by gavage
      to F344 rats and B6C3F1 mice.
AB  - Methyleugenol, a food flavor and fragrance agent, was tested for toxicity in male
      and female F344/N rats and B6C3F1 mice. Groups of 10 males and 10 females per sex
      per species were administered 0, 10, 30, 100, 300 or 1000 mg methyleugenol/kg
      body weight in 0.5% aqueous methylcellulose by gavage, 5 days per week for 14
      weeks. Additional groups of rats and mice of each sex were dosed similarly and
      used for hematology and clinical chemistry studies. Groups of 10 male and 10
      female rats and mice received the vehicle by gavage on the same dosing schedule
      and served as vehicle controls. For serum gastrin, gastric pH and cell
      proliferation studies groups of 10 female rats were given 0, 37, 75 or 150 mg/kg,
      once daily 5 days per week for 30 or 90 days or 300 or 1000 mg/kg for 30 days;
      male mice were given 0, 9, 18.5, 37, 75, 150 or 300 mg/kg for 30 or 90 days. For
      the gastrin, pH and cell proliferation studies, groups of 10 female rats and 10
      male mice were given the vehicle for 30 or 90 days and served as controls.
      Methyleugenol administration to rats induced erythrocyte microcytosis and
      thrombocytosis in male and female rats. It also caused an increase in serum
      alanine aminotransferase and sorbitol dehydrogenase activities and bile acid
      concentration, suggesting hepatocellular injury, cholestasis or altered hepatic
      function. Additionally, methyleugenol induced hypoproteinemia and
      hypoalbuminemia, evidenced by decreased total protein and albumin concentrations
      in both male and female rats, suggesting in inefficiency of dietary protein
      utilization due to methyleugenol-induced toxic effects on the liver and glandular
      stomach of rats and mice. The increase in gastrin and gastric pH of rats and mice
      given methyleugenol suggests that gastrin feedback was impaired and resulted in
      conditions not conducive to protein digestion. In rats, methyleugenol caused an
      increase in the incidences of hepatocyte cytologic alteration, cytomegaly,
      Kupffer cell pigmentation, mixed foci of cellular alteration and bile duct
      hyperplasia of the liver and atrophy and chronic inflammation of the mucosa of
      the glandular stomach. In mice, it caused an increase in the incidence of
      cytologic alteration, necrosis, bile duct hyperplasia and subacute inflammation
      of the liver and atrophy, degeneration, necrosis, edema, mitotic alteration, and
      cystic glands of the fundic region of the glandular stomach. The increased
      incidences of adrenal gland cortical hypertrophy and/or cytoplasmic alteration in
      the submandibular salivary glands, adrenal glands, testis and uterus of rats were
      considered secondary to the chemical-related effects observed in the liver and
      glandular stomach. Based on mortality, body weight gain, clinical chemistry and
      gross and microscopic evaluation of tissues of rats and mice, the no-observed
      effect level (NOEL) of methyleugenol for both species was estimated at 10 mg/kg.

PMID- 11295479
TI  - Chronic study of diacylglycerol oil in rats.
AB  - The objective of the present study was to evaluate the effects of diacylglycerol
      oil following long-term administration to rats. Diacylglycerol oil is an edible
      oil with comparable taste and physicochemical properties of several naturally
      occurring oils. Diacylglycerol oil can be used as a replacement for any generally
      used edible oil in the home and has been approved for use in cooking oil in
      Japan. Male and female Sprague-Dawley rats were divided into four groups and fed
      low-fat (1.7%) basal diets containing an edible oil composed of rapeseed, corn,
      high linoleic safflower and high oleic safflower oils at 5.3% (control group 1);
      an edible oil composed of rapeseed and soybean oils at 5.3% (control group 2);
      diacylglycerol oil at 2.65% plus edible oil composed of rapeseed, corn, high
      linoleic safflower and high oleic safflower oils at 2.65% (low-dose group); and
      diacylglycerol oil at 5.3% (high-dose group) for 2 years. Interim sacrifices were
      conducted at weeks 30 and 77 and the study was terminated following 105 weeks of
      feeding. No compound-related effects were noted on clinical signs, body weights,
      food consumption, cumulative survival rates, hematology, blood chemistry,
      urinalysis, organ weights or on microscopic non-neoplastic changes. Compared to
      control group 2, but not control group 1, there was a significant increase in the
      number of high-dose group females with either benign or malignant epithelial
      mammary gland neoplasms. These changes were not considered biologically
      significant, because the tumor incidence was not similar in control group 1 and
      2, and the neoplastic findings were not dose related. In summary, the two-year
      chronic rat study revealed no toxicologically significant or treatment-related
      effects of diacylglycerol oil consumption at levels of up to 5.3% in the diet.

PMID- 11295480
TI  - Comparison of estimated daily per capita intakes of flavouring substances with no
      observed-effect levels from animal studies.
AB  - A study was conducted to determine the margins of safety between no-observed
      effect levels (NOELs) and daily per capita intake of flavouring substances
      evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) using
      the safety evaluation procedure for flavouring substances. The safety evaluation
      procedure provides a practical method for integrating data on intake, structure
      activity relationships, metabolism and toxicity to evaluate flavouring
      substances. The comparison of NOELs to intake reinforces the fact that the
      margins of safety between intake of flavouring substances and their
      representative NOELs is very large. 98% of flavouring substances have margins of
      safety greater than 1000, illustrating that even if intake was underestimated by
      several fold, in almost every case, a wide margin of safety would still exist.

PMID- 11295481
TI  - Predicting migration of trace amounts of styrene in poly(styrene) below the glass
      transition temperature.
AB  - The use of general purpose polystyrene (GPPS) as food packaging material is
      widespread. Therefore, the rate of migration of the styrene in GPPS is of
      interest in order to predict the potential exposure of consumers to styrene.
      Studies have shown a relatively weak dependence of the diffusion coefficient on
      the residual styrene content, and a strong dependence on temperature. We have
      compared the predictions of the free-volume theory with experimentally measured
      diffusivity data. The predictions and the measured values are observed to be
      consistent with each other. These results illustrate the capability of the free
      volume theory of transport to predict the diffusivity of trace amounts of
      impurity in a glassy polymer.

PMID- 11295482
TI  - Genotoxic effect of monocrotophos to sentinel species using comet assay.
AB  - Monocrotophos is the single largest selling agrochemical in India. Sensitive
      biomarkers to study the genotoxic effects caused by monocrotophos in aquatic
      organisms, especially fish, are lacking. The fish used in this study are Tilapia
      mossambica, which are edible, commercially valuable and distributed all over
      India. The objective of this study was to study DNA strand breaks induced by
      monocrotophos in T. mossambica in vivo using single-cell micro gel
      electrophoresis/comet assay. Tilapia were treated orally with 0.313, 0.625, 1.25,
      1.875, 2.5, 3.125, 3.75 and 4.375 ppm of monocrotophos and the assay was
      performed on nucleated erythrocytes after 24, 48, 72 and 96 h. A significant
      increase in mean comet tail-length (5.21-7.46 microM), indicating DNA damage, was
      observed at all the doses with monocrotophos when compared to controls (3.36
      microM). The mean tail-length showed a dose-related increase and time-dependent
      decrease. The maximum increase in mean comet tail-length was observed at 24 h.
      Relative to these effects, reductions in mean comet tail-length were seen at 48
      and 72 h. By 96 h, values had returned to control levels at all doses, indicating
      repair of the damaged DNA and/or loss of heavily damaged cells. The study reveals
      that the comet assay is a sensitive and rapid method to detect genotoxicity of
      monocrotophos and other environmental pollutants in sentinel species.

PMID- 11295483
TI  - Developmental toxicity of orally administered thiabendazole in ICR mice.
AB  - Thiabendazole (TBZ) is a potent anthelmintic and fungicide used in the treatment
      of parasitic infections in humans and domestic animals and post-harvest
      protection of agricultural commodities. TBZ is not teratogenic or selectively
      foetotoxic in rats or rabbits, in contrast to several other benzimidazole
      derivatives. However, when administered orally to pregnant (Jcl:ICR) mice at
      lethal dosages, malformations were observed in treated fetuses. To assess whether
      the effects found in this previous study were attributable to maternal toxicity
      or TBZ the present study was conducted. TBZ doses of 25, 100 or 200 mg/kg/day
      were selected based on a preliminary range-finding study in which maternotoxicity
      was evident at doses of 200 mg/kg/day or above. The compound was administered
      during gestation days 6-15 as a solution in olive oil. Caesarean sections were
      completed on gestation day 18 and complete fetal examinations conducted.
      Decreases in maternal weight gain relative to controls were found at doses of 100
      mg/kg/day or above, which paralleled decreases in foetal weights in these same
      dose groups. However, there were no treatment-related external, visceral or
      skeletal anomalies in any treatment group. Therefore, TBZ was not teratogenic or
      selectively foetotoxic in mice, with no-observed-effect levels (NOEL) of 25 and
      greater than 200 mg/kg/day for maternal and fetal weight effects and
      teratogenicity, respectively. These results indicate that foetal effects noted in
      previous studies in mice were probably secondary to severe maternal toxicity.

PMID- 11295484
TI  - Strain differences in haematological response to chloramphenicol succinate in
      mice: implications for toxicological research.
AB  - Much toxicological research continues to be done using genetically undefined
      "outbred" stocks of mice and rats, although the case for using isogenic strains
      has been made repeatedly in the literature over a period of more than two
      decades. Also, very few studies are conducted using more than one strain, with
      the result that genetic variation in response is seldom apparent to the
      investigator. Here we report qualitative and quantitative strain differences in
      the haematological response to chloramphenicol succinate (CAPS) when administered
      by gavage at 500-2500 mg/kg for 7 days, to four inbred strains of mouse (C3H/He,
      CBA/Ca, BALB/c and C57BL/6) and one outbred stock (CD-1). CAPS caused anaemia and
      reticulocytopenia in all mouse strains, and leucopenia in the inbred strains but
      not in the outbred CD-1 stock. All four inbred strains showed significant
      (P<0.01) responses to CAPS at lower dose levels than in CD-1 mice, which were
      phenotypically more variable than the inbred animals. A simulated experiment,
      using a sample of records from the present study, showed that the use of two mice
      at each dose level using CD-1, CBA, BALB/c and C57BL/6 (48 total mice), would
      have given a more sensitive experiment than the use of 47 CD-1 mice alone, and
      would also have shown that the response is partly strain dependent. These studies
      provide additional evidence that inbred strains, because of their greater
      sensitivity and other valuable properties, should be more widely used in
      toxicology.

PMID- 11295485
TI  - Comparison of AIN-76A and AIN-93G diets: a 13-week study in rats.
AB  - Either purified or cereal-based diets may be used for toxicity testing in rats.
      Purified diets have advantages in terms of flexibility of formulation to meet
      specific study objectives and also assurance of relatively low levels of
      contaminants (e.g. heavy metals and pesticides). The American Institute of
      Nutrition recommended that the widely used purified diet AIN-76A be replaced by
      two newer diets, AIN-93G (for use during rapid growth, pregnancy and lactation)
      and AIN-93M (maintenance diet). The present study compared AIN-76A and AIN-93G by
      feeding these diets for 13 weeks to male and female rats. A cereal-based diet was
      also included for reference purposes. The groups fed purified diets had higher
      serum cholesterol and triglyceride levels than the chow-fed group. An increased
      incidence and severity of renal tubular mineralization in the purified diet
      groups was not observed in this study (in contrast to other published studies
      where rats were fed AIN-76A). Several histopathologic observations, including
      eosinophilic gastritis and mucification of gastric glands of the glandular
      stomach, occurred at higher rates in the AIN-76A group than the other dietary
      treatments. Hepatocellular fatty changes occurred in the purified diet groups at
      a significantly higher rate than in the chow diet group. In conclusion, AIN-93G
      is an appropriate diet for use in rat safety evaluation studies.

PMID- 11295486
TI  - Quantitative measurement of the nitrate reductase activity in the human oral
      cavity.
AB  - To quantitatively characterise the nitrate reductase activity in the human oral
      cavity, a new assay based on holding 20 ml of 10 mg nitrate-N/L solution in the
      mouth was developed. The mouth assay appeared to relate primarily to the oral
      cavity surface rather than to the saliva. Nitrite formation in the assay was 50
      100 times higher compared to in vitro incubation. In the proposed assay, the
      nitrite formation linearly increased over a period of 3 min. The average nitrate
      reductase activity in the oral cavity of 20 subjects was 2.39+/-1.52 microg
      nitrite-N formed/person x min. The nitrate reductase activity measured for two
      subjects at different hours varied about 15% for the same subject. The average
      nitrate reductase activity measured in June for 10 subjects (3.43+/-1.75 microg
      N/person x min) was significantly higher than that measured in November for 10
      other subjects (1.54+/-0.46 microg-N/person x min). Therefore, the nitrate
      reductase activity in the oral cavity appears to be influenced by the seasonal
      conditions. Although the amounts of nitrite formed in the mouth assay increased
      with increasing levels of nitrate, the rate of nitrate to nitrite reduction
      decreased with increasing levels of nitrate. The nitrite formation was also
      affected by the pH, with an optimal pH about 8. The nitrite formation was not
      influenced by uptake in the mouth of glucose, L-ascorbic acid and L-arginine.

PMID- 11295487
TI  - Lack of correlation between cigarette mainstream smoke particulate phase radicals
      and hydroquinone yield.
AB  - Evidence suggests that when compared with non-smokers, cigarette smokers are
      exposed to an increased burden of free radicals from both the vapor phase and
      particulate phase of the cigarette smoke aerosol. In this study, primary emphasis
      was placed on the free radicals found in the particulate phase. Published reports
      hypothesize that the particulate phase free radicals of cigarette mainstream
      smoke (MS) condensate consist of a hydroquinone/semiquinone/quinone shuttle.
      However, our results do not suggest that there is a positive correlation between
      the smoke yield of hydroquinone and the presence of particulate phase free
      radicals. First, 10-fold reductions in MS hydroquinone yield were obtained when
      KNO3 was applied to the surface of tobacco of an American blended cigarette.
      Surprisingly, there was no significant corresponding change in the yield of
      particulate phase radicals. Second, in experiments testing MS from low and high
      hydroquinone-yielding tobaccos there was no consistent corresponding relationship
      between hydroquinone and particulate phase radical yields. In one series of
      blends there was at best an inverse relationship between hydroquinone and
      particulate phase radical yields. In contrast with the published literature, we
      conclude that the particular compound or compounds driving particulate phase free
      radical formation are currently unknown. An additional experiment reported here
      suggested that components of the water soluble extract of burley tobacco may be
      driving the formation of particulate phase free radicals.

PMID- 11295488
TI  - 20S proteasome biogenesis.
AB  - 26S proteasomes are multi-subunit protease complexes responsible for the turnover
      of short-lived proteins. Proteasomal degradation starts with the autocatalytic
      maturation of the 20S core particle. Here, we summarize different models of
      proteasome assembly. 20S proteasomes are assembled as precursor complexes
      containing alpha and unprocessed beta subunits. The propeptides of the beta
      subunits are thought to prevent premature conversion of the precursor complexes
      into matured particles and are needed for efficient beta subunit incorporation.
      The complex biogenesis is tightly regulated which requires additional components
      such as the maturation factor Ump1/POMP, an ubiquitous protein in eukaryotic
      cells. Ump1/POMP is associated with precursor intermediates and degraded upon
      final maturation. Mammalian proteasomes are localized all over the cell, while
      yeast proteasomes mainly localize to the nuclear envelope/endoplasmic reticulum
      (ER) membrane network. The major localization of yeast proteasomes may point to
      the subcellular place of proteasome biogenesis.

PMID- 11295489
TI  - Subtypes of 20S proteasomes from skeletal muscle.
AB  - 20S proteasomes from tissues and cells are a mixture of several subtypes. From
      rat skeletal muscle we have tentatively separated six different subtypes of 20S
      proteasomes purified from rat skeletal muscle by high-resolution anion exchange
      chromatography. Immunoblot analysis using antibodies to the beta-subunits LMP2,
      LMP7 and their constitutive counterparts delta and MB1 revealed that two of the
      three major subtypes (subtypes I and II) are constitutive proteasomes, whereas
      two of the three minor subtypes belong to the subpopulation of immuno
      proteasomes. Subtype III and IV are intermediate-type proteasomes. Enzymological
      characterisation of the six subtypes revealed clearly different V(max) values for
      hydrolysis of fluorogenic peptide substrates as well as significantly different
      activities measured with a 25-mer polypeptide of the murine cytomegalovirus IE
      pp89 protein as substrate. Our data show that the properties of 20S proteasomes
      isolated from a given tissue or cells are always the average of the properties of
      the whole set of proteasome subtypes.

PMID- 11295490
TI  - Degradation of oxidized proteins by the 20S proteasome.
AB  - Oxidatively modified proteins are continuously produced in cells by reactive
      oxygen and nitrogen species generated as a consequence of aerobic metabolism.
      During periods of oxidative stress, protein oxidation is significantly increased
      and may become a threat to cell survival. In eucaryotic cells the proteasome has
      been shown (by purification of enzymatic activity, by immunoprecipitation, and by
      antisense oligonucleotide studies) to selectively recognize and degrade mildly
      oxidized proteins in the cytosol, nucleus, and endoplasmic reticulum, thus
      minimizing their cytotoxicity. From in vitro studies it is evident that the 20S
      proteasome complex actively recognizes and degrades oxidized proteins, but the
      26S proteasome, even in the presence of ATP and a reconstituted functional
      ubiquitinylating system, is not very effective. Furthermore, relatively mild
      oxidative stress rapidly (but reversibly) inactivates both the ubiquitin
      activating/conjugating system and 26S proteasome activity in intact cells, but
      does not affect 20S proteasome activity. Since mild oxidative stress actually
      increases proteasome-dependent proteolysis (of oxidized protein substrates) the
      20S 'core' proteasome complex would appear to be responsible. Finally, new
      experiments indicate that conditional mutational inactivation of the E1 ubiquitin
      activating enzyme does not affect the degradation of oxidized proteins, further
      strengthening the hypothesis that oxidatively modified proteins are degraded in
      an ATP-independent, and ubiquitin-independent, manner by the 20S proteasome. More
      severe oxidative stress causes extensive protein oxidation, directly generating
      protein fragments, and cross-linked and aggregated proteins, that become
      progressively resistant to proteolytic digestion. In fact these aggregated, cross
      linked, oxidized proteins actually bind to the 20S proteasome and act as
      irreversible inhibitors. It is proposed that aging, and various degenerative
      diseases, involve increased oxidative stress (largely from damaged and electron
      'leaky' mitochondria), and elevated levels of protein oxidation, cross-linking,
      and aggregation. Since these products of severe oxidative stress inhibit the 20S
      proteasome, they cause a vicious cycle of progressively worsening accumulation of
      cytotoxic protein oxidation products.

PMID- 11295491
TI  - The unfolding of substrates and ubiquitin-independent protein degradation by
      proteasomes.
AB  - 26S proteasomes are composed of a 20S proteolytic core and two ATPase-containing
      19S regulatory particles. To clarify the role of these ATPases in proteolysis, we
      studied the PAN complex, the archaeal homolog of the 19S ATPases. When ATP is
      present, PAN stimulates protein degradation by archaeal 20S proteasomes. PAN is a
      molecular chaperone that catalyzes the ATP-dependent unfolding of globular
      proteins. If 20S proteasomes are present, this unfoldase activity is linked to
      degradation. Thus PAN, and presumably the 26S ATPases, unfold substrates and
      facilitate their entry into the 20S particle. 26S proteasomes preferentially
      degrade ubiquitinated proteins. However, we found that calmodulin (CaM) and
      troponin C are degraded by 26S proteasomes without ubiquitination. Ca(2+)-free
      native CaM and in vitro 'aged' CaM are degraded faster than the Ca(2+)-bound
      form. Ubiquitination of CaM does not enhance its degradation. Degradation of
      ovalbumin normally requires ubiquitination, but can occur without ubiquitination
      if ovalbumin is denatured. The degradation of these proteins still requires ATP
      and the 19S particle. Thus, ubiquitin-independent degradation by 26S proteasomes
      may be more important than generally assumed.

PMID- 11295492
TI  - Antizyme, a mediator of ubiquitin-independent proteasomal degradation.
AB  - Ornithine decarboxylase (ODC) is among the small set of proteasome substrates
      that is not ubiquitinated. It is instead degraded in conjunction with the protein
      antizyme (AZ). ODC and AZ are participants in a regulatory circuit that restricts
      pools of polyamines, the downstream products of ODC enzymatic activity.
      Functional studies using directed mutagenesis have identified regions of ODC and
      AZ required for the process of ODC degradation. Within ODC, there is a region
      that is required for AZ binding which lies on the surface of an alpha-beta barrel
      forming one domain of the ODC monomer. A carboxy-terminal ODC domain is needed
      for both AZ-dependent and AZ-independent degradation. Within AZ, the carboxy
      terminal half molecule is sufficient for binding to ODC, but an additional domain
      found within the AZ amino terminus must be present for stimulation of ODC
      degradation by the proteasome. Recently, the AZs have been found to consist of an
      ancient gene family. Within vertebrate species, multiple isoforms are found, with
      distinct functions that remain to be sorted out. Although AZ homologs have been
      found in some yeast species, homology searches have failed to identify an AZ
      homolog in Saccharomyces cerevisiae. Nevertheless, the close parallel between
      polyamine-induced ODC degradation in S. cerevisiae and in animal cells suggests
      that this organism will also be found to harbor an AZ-like protein.

PMID- 11295493
TI  - The substrate translocation channel of the proteasome.
AB  - The core particle (CP) of the yeast proteasome is composed of four heptameric
      rings of subunits arranged in a hollow, barrel-like structure. We have found that
      the CP is autoinhibited by the N-terminal tails of the outer (alpha) ring
      subunits. Crystallographic analysis showed that deletion of the tail of the
      alpha3 subunit opens a channel into the proteolytically active interior chamber
      of the CP, thus derepressing peptide hydrolysis. In the latent state of the
      particle, the tails prevent substrate entry by imposing topological closure on
      the CP. Inhibition by the alpha subunit tails is relieved upon binding of the
      regulatory particle to the CP to form the proteasome holoenzyme. Opening of the
      CP channel by assembly of the holoenzyme is regulated by the ATPase domain of
      Rpt2, one of 17 subunits in the RP. Thus, open-channel mutations in CP subunits
      suppress the closed-channel phenotype of an rpt2 mutant. These results identify a
      specific mechanism for allosteric regulation of the CP by the RP.

PMID- 11295494
TI  - Genetic dissection of the yeast 26S proteasome: cell cycle defects caused by the
      Deltarpn9 mutation.
AB  - Rpn9 is one of the subunits of the regulatory particle of the yeast 26S
      proteasome and is needed for stability or efficient assembly of the 26S
      proteasome. As anticipated from the fact that the rpn9 disruptant grew at 25
      degrees C but arrested in G2/M phase at 37 degrees C, the CDK inhibitor Sic1p was
      found to be degraded at the G1/S boundary in the Deltarpn9 cells. The degradation
      of the anaphase inhibitor Pds1p was delayed in the Deltarpn9 cells. Clb2p in M
      phase, as well as that ectopically expressed in G1 and S phases, was degraded
      more slowly in the Deltarpn9 cells than in the wild type cells, indicating that
      the 26S proteasome lacking Rpn9 uses Sic1p as a better substrate than Pds1p and
      Clb2p. These results, in addition to the fact that multiubiquitinated proteins
      were accumulated in the Deltarpn9 cells incubated at 37 degrees C, strongly
      suggest that Rpn9 is involved in the proteolysis of a subset of the substrates
      degraded by the 26S proteasome. The Deltarpn9 Deltapds1 double mutant was unable
      to elongate spindle at a restrictive temperature, suggesting that some protein(s)
      other than Scc1 (cohesin) should be degraded during progression of anaphase.

PMID- 11295496
TI  - Control of IkappaBalpha proteolysis by the ubiquitin-proteasome pathway.
AB  - It has recently been determined that the proteolytic destruction of IkappaB
      (inhibitor of NF-kappaB) by the ubiquitin-proteasome system plays a key role in
      the immediate elimination of IkappaB from the IkappaB-(NF-kappaB) complex which
      allows nuclear translocation of free NF-kappaB, thus leading to activation of a
      multitude of target genes. The SCF(Fbw1) (composed of Skp1, Cul-1, Roc1, and
      Fbw1) complex, identified as an IkappaBalpha-E3 ligase, binds and ubiquitylates
      IkappaBalpha phosphorylated by IkappaB kinase that has been activated in response
      to extracellular signals. The generating poly-ubiquitin chain is finally
      recognized by the 26S proteasome for ultimate degradation. In this NF-kappaB
      signalling pathway, it becomes clear that the SCF(Fbw1) activity is enhanced by a
      ubiquitin-like protein NEDD8 (equivalent to Rub1) that modifies Cul-1 in a manner
      analogous to ubiquitylation, and consequently, IkappaBalpha proteolysis is
      induced. NEDD8 is a new regulator of the SCF ubiquitin-ligase, functioning as a
      covalent modifier for proteolytic targeting at a physiological level.

PMID- 11295495
TI  - Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor
      protein p105.
AB  - In most cases, target proteins of the ubiquitin system are completely degraded.
      In several exceptions, such as the first step in the activation of the
      transcriptional regulator NF-kappaB, the substrate, the precursor protein p105,
      is processed in a limited manner to yield the active subunit p50. p50 is derived
      from the N-terminal domain of p105, whereas the C-terminal domain is degraded.
      The mechanisms involved in this unique process have remained elusive. We have
      shown that a Gly-rich region (GRR) at the C-terminal domain of p50 is one
      important processing signal and that it interferes with processing of the
      ubiquitinated precursor by the 26S proteasome. Also, amino acid residues 441-454
      are important for processing under non-stimulated conditions. Lys 441 and 442
      serve as ubiquitination targets, whereas residues 446-454 may serve as a ligase
      recognition motif. Following IkappaB kinase (IKK)-mediated phosphorylation, the C
      terminal domain of p105, residues 918-934, recruits the SCF(beta-TrCP) ubiquitin
      ligase, and ubiquitination by this complex leads to accelerated processing. The
      two sites appear to be recognized under different physiological conditions by two
      different ligases, targeting two distinct recognition motifs. We have shown that
      ubiquitin conjugation and processing of a series of precursors of p105 that lack
      the C-terminal IKK phosphorylation/TrCP binding domain, is progressively
      inhibited with increasing number of ankyrin repeats. Inhibition is due to docking
      of active NF-kappaB subunits to the ankyrin repeat domain in the C-terminal half
      of p105 (IkappaBgamma). Inhibition is alleviated by phosphorylation of the C
      terminal domain that leads to ubiquitin-mediated degradation of the ankyrin
      repeat domain and release of the anchored subunits. We propose a model that may
      explain the requirement for two sites: a) a basal site that may be involved in co
      translational processing prior to the synthesis of the ankyrin repeat domain; and
      b) a signal-induced site that is involved in processing/degradation of the
      complete molecule following cell activation, with rapid release of stored,
      transcriptionally active subunits.

PMID- 11295497
TI  - Degradation of cellular and viral Fos proteins.
AB  - c-Fos proto-oncoprotein is a short-lived transcription factor with oncogenic
      potential. We have shown that it is massively degraded by the proteasome in vivo
      under various experimental conditions. Other proteolytic systems including
      lysosomes and calpains, might, however, also marginally operate on it. Although
      there is evidence that c-Fos can be ubiquitinylated in vitro, the unambiguous
      demonstration that ubiquitinylation is necessary for its addressing to the
      proteasome in vivo is still lacking. c-Jun, one of the main dimerization partners
      of c-Fos within the AP-1 transcription complex, is also an unstable protein. Its
      degradation is clearly proteasome- and ubiquitin-dependent in vivo.
      Interestingly, several lines of evidence indicate that the addressing of c-Fos
      and c-Jun to the proteasome is, at least in part, governed by different
      mechanisms. c-Fos has been transduced by two murine osteosarcomatogenic
      retroviruses under mutated forms which are more stable and more oncogenic. The
      stabilization is not simply accounted for by simple deletion of c-Fos main
      destabilizer but, rather, by a complex balance between opposing destabilizing and
      stabilizing mutations. Though mutations in viral Fos proteins confer full
      resistance to proteasomal degradation, stabilization is limited because mutations
      also entail sensitivity to an unidentified proteolytic system. This observation
      is consistent with the idea that Fos-expressing viruses have evolved to ensure
      control protein levels to avoid high protein accumulation-linked apoptosis. In
      conclusion, the unveiling of the complex mechanism network responsible for the
      degradation of AP-1 family members is still at its beginning and a number of
      issues regarding the regulation of this process and the addressing to the
      proteasome are still unresolved.

PMID- 11295498
TI  - Regulation of proteasome complexes by gamma-interferon and phosphorylation.
AB  - Proteasomes play a major role in non-lysosomal proteolysis and also in the
      processing of proteins for presentation by the MHC class I pathway. In animal
      cells they exist in several distinct molecular forms which contribute to the
      different functions. 26S proteasomes contain the core 20S proteasome together
      with two 19S regulatory complexes. Alternatively, PA28 complexes can bind to the
      ends of the 20S proteasome to form PA28-proteasome complexes and PA28-proteasome
      19S hybrid complexes have also been described. Immunoproteasome subunits occur in
      26S proteasomes as well as in PA28-proteasome complexes. We have found
      differences in the subcellular distribution of the different forms of
      proteasomes. The gamma-interferon inducible PA28 alpha and beta subunits are
      predominantly located in the cytoplasm, while 19S regulatory complexes (present
      at significant levels only in 26S complexes) are present in the nucleus as well
      as in the cytoplasm. Immunoproteasomes are greatly enriched at the endoplasmic
      reticulum (ER) where they may facilitate the generation of peptides for transport
      into the lumen of the ER. We have also investigated the effects of gamma
      interferon on the levels and subcellular distribution of inducible subunits and
      regulator subunits. In each case gamma-interferon was found to increase the level
      but not to alter the distribution. Several subunits of proteasomes are
      phosphorylated including alpha subunits C8 (alpha7) and C9 (alpha3), and ATPase
      subunit S4 (rpt2). Our studies have shown that gamma-interferon treatment
      decreases the level of phosphorylation of proteasomes. We have investigated the
      role of phosphorylation of C8 by casein kinase II by site directed mutagenesis.
      The results demonstrate that phosphorylation at either one of the two sites is
      essential for the association of 19S regulatory complexes and that the ability to
      undergo phosphorylation at both sites gives the most efficient incorporation of
      C8 into the 26S proteasome.

PMID- 11295499
TI  - Interferon-gamma inducible exchanges of 20S proteasome active site subunits: why?
AB  - When cells are stimulated with the cytokines IFN-gamma or TNF-alpha, the
      synthesis of three proteasome subunits LMP2 (beta1i), LMP7 (beta5i), and MECL-1
      (beta2i) is induced. These subunits replace the three subunits delta (beta1), MB1
      (beta5), and Z (beta2), which bear the catalytically active sites of the
      proteasome, during proteasome neosynthesis. The cytokine-induced exchanges of
      three active site subunits of a complex protease is unprecedented in biology and
      one may expect a strong functional driving force for this system to evolve. These
      cytokine-induced replacements of proteasome subunits are believed to favour the
      production of peptide ligands of major histocompatibility complex (MHC) class I
      molecules for the stimulation of cytotoxic T cells. Although the peptide
      production by constitutive proteasomes is able to maintain peptide-dependent MHC
      class I cell surface expression in the absence of LMP2 and LMP7, these subunits
      were recently shown to be pivotal for the generation or destruction of several
      unique epitopes. In this review we discuss the recent data on LMP2/LMP7/MECL-1
      dependent epitope generation and the functions of each of these subunit
      exchanges. We propose that these subunit exchanges have evolved not only to
      optimize class I peptide loading but also to generate LMP2/LMP7/MECL-1-dependent
      epitopes in inflammatory sites which are not proteolytically generated in
      uninflamed tissues. This difference in epitope generation may serve to better
      stimulate T cells in the sites of an ongoing immune response and to avoid
      autoimmunity in uninflamed tissues.

PMID- 11295501
TI  - History and prospects: symposium on organisms with slow aging.
AB  - We discuss the background concepts which lead to this issue of Experimental
      Gerontology. On one hand, genetic and molecular studies of short-lived worms,
      flies, and mice are yielding remarkable discoveries on gene systems that regulate
      the life span. On the other hand, little is known about the nature of aging in
      other vertebrates, with life spans extending into the human range or beyond the
      record 122y human life span, which may have aging processes that are so slow as
      to be 'negligible'. We point out that organisms with these vastly different life
      spans have essentially identical cells within an evolutionary group and that the
      cellular tool kit that existed by 600 million years ago allowed the evolution of
      life spans ranging up to one million-fold difference in length. The possibility
      of negligible senescence has not been widely discussed, and may be in conflict
      with mathematical deductions from population genetics theory. We propose minimal
      criteria for the lack of senescence: (1) no observable increase in age-specific
      mortality rate or decrease in reproduction rate after sexual maturity; and (2) no
      observable age-related decline in physiological capacity or disease resistance.
      We also introduce some of the species discussed in subsequent chapters which are
      unfamiliar models to most biomedical researchers.

PMID- 11295500
TI  - Molecular dissection of the 11S REG (PA28) proteasome activators.
AB  - The proteasome activators known as 11S REG or PA28 were discovered about 10 years
      ago. They are homo- or heteroheptameric rings that bind to the ends of 20S
      proteasomes and activate cleavage of peptides but not folded proteins. In this
      article, we focus on structural features of three homologous REG subunits (termed
      alpha, beta, gamma) that contribute to their oligomerization, proteasome binding
      and proteasome activation. We review a number of published studies on the
      biochemical properties of REGs and present new results in which N-terminal
      sequences and sequences flanking REG activation loops have been exchanged between
      homologs. Characterization of these chimeras and previously constructed C
      terminal chimeras reveal that N-terminal and loop flanking sequences affect
      oligomerization, whereas C-terminal sequences are essential for proteasome
      binding. None of these regions is responsible for the broad activation
      specificity of REGs alpha/beta versus the narrow specificity of REGgamma. Rather,
      mutation in a single residue lining the channel through the REGgamma heptamer
      changes the activation property of the gamma homolog to match that of REGs alpha
      and beta.

PMID- 11295502
TI  - An experimental paradigm for the study of slowly aging organisms.
AB  - An experimental paradigm for the study of mechanisms of resistance to aging in
      long-lived organisms has been developed. The paradigm assumes, in concert with
      accumulating empirical data, that resistance to the aging processes at the
      organismal level will be reflected in resistance to various stressors at the
      cellular level. The advantage of this paradigm is that it requires neither the
      long-term monitoring of individuals nor the use of exceptionally old individuals.
      The research approach consists of: (1) verifying that primary cell cultures from
      the long-lived organism exhibit better resistance to key stressors than cells
      from related, short-lived organisms; (2) assessing differences in gene-expression
      before and after stress exposure in cultured cells from the long- and short-lived
      species in order to identify key genes involved in the stress-resistance
      response; (3) transfecting putative key genes from long-lived species into cells
      or cell lines of defined stress-resistance and hope to observe that the stress
      resistance phenotype has thereby been transferred with the gene(s); (4)
      generating transgenic model animals containing the gene(s) of interest and look
      for extended life/health span.

PMID- 11295503
TI  - From cells to organisms: can we learn about aging from cells in culture?
AB  - Can studying cultured cells inform us about the biology of aging? The idea that
      this may be was stimulated by the first formal description of replicative
      senescence. Replicative senescence limits the proliferation of normal human cells
      in culture, causing them to irreversibly arrest growth and adopt striking changes
      in cell function. We now know that telomere shortening, which occurs in most
      somatic cells as a consequence of DNA replication, drives replicative senescence
      in human cells. However, rodent cells also undergo replicative senescence,
      despite very long telomeres, and DNA damage, the action of certain oncogenes and
      changes in chromatin induce a phenotype similar to that of replicatively
      senescent cells. Thus, replicative senescence is an example of the more general
      process of cellular senescence, indicating that the telomere hypothesis of aging
      is a misnomer, Cellular senescence appears to be a response to potentially
      oncogenic insults, including oxidative stress. The growth arrest almost certainly
      suppresses tumorigenesis, at least in young organisms, whereas the functional
      changes may contribute to aging, although this has yet to be critically tested.
      Thus, cellular senescence may be an example of antagonistic pleiotropy. Cross
      species comparisons suggest there is a relationship between the senescence of
      cells in culture and organismal life span, but the relationship is neither
      quantitative nor direct.

PMID- 11295504
TI  - Oxidative biochemical markers; clues to understanding aging in long-lived
      species.
AB  - Clues as to why long-lived species live so much longer than short-lived species
      may reside in the amount of reactive oxygen species (ROS) produced and their
      effect on damaging cell components (especially proteins) and alterations of
      crucial cellular processes. Rigorous evaluation of these concepts required
      critical comparisons of oxidative damage markers and/or parameters with assess
      difference in ROS flux and the critical age-modifying processes they influence.
      The limited experimental comparative results available implicate that ROS
      production per unit weight of total oxygen consumed is much less in the longer
      lived species than in shorter-lived species. Mitochondria are the major site of
      ROS production. They are also the functional nexus for intracellular signaling
      thus modulating stress and growth factor mediated cellular survival,
      proliferation and apoptotic processes. Mitochondrial DNA mutations, perhaps
      caused by ROS, increase with age. Mutant mitochondria possess comparative
      replicative advantage, which leads to age-specific intracellular swarms. General
      inflammatory stress tends to increase with age. Disruption in coordinated cell-to
      cell signaling triggered by alterations in intracellular signaling may be the
      basis of the age-related increases in tissue inflammation, which may explain some
      of the differences between long-lived species and short-lived species.

PMID- 11295505
TI  - Evolutionary theories of ageing applied to long-lived organisms.
AB  - Ageing can evolve by mutation accumulation and pleiotropy (trade-offs). The
      relative prevalence of these two mechanisms is important for determining the
      likelihood that mechanisms of ageing are homologous in distantly related
      organisms, and hence the relevance of long-lived organisms to general mechanisms
      of ageing. Experimental work with Drosophila, examining the properties of
      standing genetic variation and mutations that accumulate in real time, has
      provided little evidence in favour of a role for mutation accumulation, but
      considerable support for the importance of trade-offs, particularly between early
      fertility and the rate of ageing. Evidence for the roles of these two processes
      in the evolution of long-livedness can be derived from the response to selection,
      comparative studies of life history traits and testing for potential trade-offs
      at the mechanistic level.

PMID- 11295506
TI  - The paradox of great longevity in a short-lived tree species.
AB  - Thuja occidentalis is a tree species that was once thought to be relatively short
      lived (80 years). Up until 10 years ago maximum ages were considered to be near
      400 years, but such trees were thought to be rare. Research along the cliffs of
      the Niagara Escarpment has altered this view. Exceptionally slow-growing trees of
      this species have been found with ring counts to 1653 years and estimated ages to
      1890 years. Senescence is slow or absent. Injury and death is due to rockfall and
      sporadic severe drought that kills small sectors of the trees by exposing and
      killing the roots. Experiments in which colored dyes are infused into roots show
      that each tree is composed of hydraulically independent units that allow
      mortality in one part of the 'individual' with little negative effect on the
      remaining parts of the tree. The trees are small, so environmental loadings of
      ice, snow, and wind are low. Slow growth of the trees results in a much greater
      mechanical strength in the wood. Together these properties increase the ability
      of the cedars to persist on cliffs for long periods of time. The paradox of great
      longevity in this 'short-lived' tree species is explained by slow growth that
      minimizes maintenance and repair costs while maximizing durability and strength,
      combined with an internal architecture that creates functionally independent
      units within each tree.

PMID- 11295507
TI  - Does bristlecone pine senesce?
AB  - We evaluated hypotheses of senescence in old trees by comparing putative
      biomarkers of aging in Great Basin bristlecone pine (Pinus longaeva) ranging in
      age from 23 to 4713 years. To test a hypothesis that water and nutrient
      conduction is impaired in old trees we examined cambial products in the xylem and
      phloem. We found no statistically significant age-related changes in tracheid
      diameter, or in several other parameters of xylem and phloem related to cambial
      function. The hypothesis of continuously declining annual shoot growth increments
      was tested by comparing trees of varying ages in regard to stem unit production
      and elongation. No statistically significant age-related differences were found.
      The hypothesis that aging results from an accumulation of deleterious mutations
      was addressed by comparing pollen viability, seed weight, seed germinability,
      seedling biomass accumulation, and frequency of putative mutations, in trees of
      varying ages. None of these parameters had a statistically significant
      relationship to tree age. Thus, we found no evidence of mutational aging. It
      appears that the great longevity attained by some Great Basin bristlecone pines
      is unaccompanied by deterioration of meristem function in embryos, seedlings, or
      mature trees, an intuitively necessary manifestation of senescence. We conclude
      that the concept of senescence does not apply to these trees.

PMID- 11295508
TI  - Environmental effects on age-dependent mortality: a test with a perennial plant
      species under natural and protected conditions.
AB  - Most experimental studies of senescence have been done with short-lived organisms
      under controlled laboratory conditions and it is not clear whether the insights
      gained from these studies can be broadly generalized. This study was designed to
      detect senescence in a natural population and to compare the patterns of
      mortality for a single species in natural and protected conditions. It was done
      with Plantago lanceolata, a perennial plant for which the demography of a large
      population of individuals in their natural environment is relatively
      straightforward. An initial cohort of 10,000 individuals was established in the
      natural field environment. In order to separate the effects of environment- and
      age-dependent factors on mortality, an additional cohort was planted in the field
      one year later. To study the demography of mortality under protected conditions,
      a population of 1000 individuals was established in the greenhouse. The results
      of the comparative analysis of two different-aged cohorts in the field and of the
      field and greenhouse populations show that senescence patterns can be very
      plastic. The results show that senescence in the natural environment is caused by
      an increased vulnerability of older individuals to environmental stress. Under
      the protected environmental conditions of the greenhouse senescence was
      negligible.

PMID- 11295509
TI  - Aging and development in social insects with emphasis on the honey bee, Apis
      mellifera L.
AB  - Honey bee colonies typically consist of about 20-40 thousand workers, zero to few
      thousand males (drones), depending on the time of year, and a single queen, the
      mother of the colony. Workers typically live 3-6 weeks during the spring and
      summer and can live about 4months during the winter. Queens are longer lived.
      Anecdotes of queens living 2-3years are not unusual, though they normally live
      less than a year in commercial hives. Little is known about the life span of
      drones. Queens develop from fertilized eggs that are not different from the eggs
      that develop into workers. Queens are, however, twice as large, have specialized
      anatomy, live much longer, and develop faster from egg to adult. All of these
      differences are derived from differences in larval rearing environment, primarily
      nutrition. The developmental trajectory of a female larva from worker into a
      queen can be determined as late as the third day of larval development, after
      this time the developmental pathway is fixed for a worker phenotype. The total
      time of larval development is only 5-6 days, therefore, just 2-3 days of
      differential feeding can lead to profound differences in development, and
      longevity. Workers undergo age development after they become adults. Workers
      usually initiate foraging behavior when they are 2-3 weeks old. The age at which
      a worker initiates foraging is a strong determinant of her length of life. This
      is presumed to be a result of the hazards of foraging, but natural senescence
      also occurs. Some bees remain in the nest and are never observed to forage,
      thereby outliving their forager sisters. Corresponding to this behavioral
      development are changes in the sizes of glands and the production of glandular
      products, increases in biogenic amine titers within the brain, an increase in the
      volume of specific regions of the brain, and changes in the neural system that
      affect perception of stimuli, and learning and memory. These age-related changes
      in behavior are regulated by intrinsic and extrinsic factors. Genetic variation
      has been demonstrated for many of these life history and behavioral traits.
      Selection and genome mapping studies have demonstrated relationships between the
      neural system, behavior, and life history traits.

PMID- 11295510
TI  - Demographic mechanisms for the evolution of long life in social insects.
AB  - One of the most remarkable life history traits of many species of eusocial
      insects is the extraordinary longevity of their queens, with the recorded life
      span of some individuals exceeding 30 years. Surprisingly, little research has
      been conducted on either the proximate or ultimate questions concerning what
      factors favor the evolution of the long life spans in social insects. The broad
      objective of this paper is to address four sets of questions: (1) What are the
      similarities and differences in the longevity patterns among species in the four
      main groups of social insects - bees, wasps, ants and termites? (2) What is the
      evolutionary association of longevity and sociality in insects? (3) Are there
      biodemographic principles that can be derived from studies on longevity in social
      insects? and (4) What are the general implications for longevity in vertebrates,
      including humans?

PMID- 11295511
TI  - Slow aging during insect reproductive diapause: why butterflies, grasshoppers and
      flies are like worms.
AB  - Diapause is a state of arrested development accompanied by physiology for somatic
      persistence. Diapause is common in many invertebrates and is familiar to
      biogerontology in the context of Caenorhabditis elegans dauer. Among insects,
      diapause may occur in embryos, larvae, pupae or adults. At the adult stage,
      reproductive diapause arrests development of oogenesis, vitellogenesis, accessory
      gland activity, and mating behavior. Reproductive diapause has been well studied
      in monarch butterflies, several grasshoppers, and several Diptera, including
      Drosophila and Phormia. In monarchs and in grasshoppers, reproductive diapause
      physiology has been experimentally induced by the surgical removal of the corpora
      allata, the source of adult juvenile hormone; allatectomy in each case was found
      to double adult longevity. Among Drosophila, the endemic D. triauraria of Japan,
      and D. littoralis of Finland over-winter as adults in reproductive diapause. How
      D. melanogaster winter is poorly understood, but reproductive diapause can be
      cued by cool temperature. In laboratory studies, the mortality rates of post
      diapause D. melanogaster are similar to rates of newly enclosed, young flies.
      This implies that senescence during diapause is slow or negligible. Slow aging
      during the diapause period may involve elevated somatic stress resistance as well
      as reallocation of resources to somatic maintenance. Reproductive diapause in
      Drosophila is proximally controlled by down regulation of juvenile hormone, a
      phenotype that is also produced by mutants of the insulin-like receptor InR,
      homologue of C. elegans daf-2. We propose neuroendocrine control of reproductive
      diapause in D. melanogaster that includes phenotypic plasticity for rates of
      senescence.

PMID- 11295512
TI  - Age determination and validation studies of marine fishes: do deep-dwellers live
      longer?
AB  - Age determination and validation studies on deep-water marine fishes indicate
      they are difficult to age and often long-lived. Techniques for the determination
      of age in individual fish includes growth-zone analysis of vertebral centra, fin
      rays and spines, other skeletal structures, and otoliths (there are three sets of
      otoliths in most bony fish semicircular canals, each of which is made of calcium
      carbonate). Most have regular increments deposited as the fish (and its
      semicircular canals) grows. The most commonly used otolith for age determination
      is the largest one called the sagitta. Age validation techniques include: (1) tag
      recapture, often combined with oxytetracycline injection and analysis in growth
      zones of bone upon recapture; (2) analysis of growth-zones over time; and (3)
      radiometric approaches utilizing a known radioactive decay series as an
      independent chronometer in otoliths from bony fishes. We briefly summarize
      previous studies using these three validation approaches and present results from
      several of our radiometric studies on deep-water, bony fishes recently subjected
      to expanding fisheries. Radiometric age validation results are presented for four
      species of scorpaenid fishes (the bank, Sebastes rufus, and bocaccio, S.
      paucispinis, rockfishes, and two thornyhead species, Sebastolobus altivelis and
      S. alascanus). In addition, our analysis of scorpaenids indicates that longevity
      increases exponentially with maximum depth of occurrence. The reason that the
      deep-water forms of scorpaenid fishes are long-lived is uncertain. Their
      longevity, however, may be related to altered physiological processes relative to
      environmental parameters like low temperature, high pressures, low light levels,
      low oxygen, and poor food resources.

PMID- 11295513
TI  - Age and longevity in fish, with consideration of the ferox trout.
AB  - In the first part of this paper, we review the evolutionary aspects of age and
      longevity in fish and then summarize the theory of maturity due to Ray Beverton.
      This theory allows one to predict age at maturity (and thus a putative point for
      the onset of senescence) from information on growth rate and mortality rate. We
      illustrate the application of this theory with data on tilapia species and then
      discuss the limitations of the theory. In the second part of the paper, we
      develop an individual based model for the ferox trout. This is a morph of brown
      trout Salmo salar that is an exception to the common notion that caloric
      restriction extends lifespan, in the sense that ferox trout achieve long life by
      eating more, not less. The model allows one to identify the role that ecological
      and biochemical adaptations play in the longevity of the ferox trout.

PMID- 11295514
TI  - The evolution of senescence in natural populations of guppies (Poecilia
      reticulata): a comparative approach.
AB  - Model organisms like Drosophila melanogaster or Caenorhabditis elegans have
      revealed genes that influence senescence and the evolvability of senescence. We
      are interested instead in evaluating why and how senescence evolves in natural
      populations. To do so, we are taking the ecological geneticist's perspective of
      comparing natural populations that differ in factors that are predicted to
      influence the evolution of senescence and are evaluating whether senescence has
      evolved in the predicted fashion. We are also manipulating the environment to
      evaluate more directly the evolution of senescence. Guppies (Poecilia reticulata)
      are found in streams throughout the Northern Range mountains of Trinidad. Natural
      populations experience large differences in mortality rate as a consequence of
      the predators with which they co-occur. We have already shown, both with
      comparative studies and manipulations of the distribution of guppies and their
      predators, that the early life history evolves very rapidly in response to these
      differences in mortality. For example, high adult mortality rates select for
      individuals that develop more rapidly, produce their first litter of young at an
      earlier age, and devote more of their available resources to reproduction for the
      remainder of their lives. These changes were predicted by independently derived
      theory. Aspects of this same theory also predict how the late life history and
      senescence should evolve. Specifically, theory predicts that the populations that
      experience low mortality rates should also experience delayed senescence and
      longer life spans relative to those that experience high mortality rates. We are
      currently evaluating these predictions with representatives from two high
      predation and two low-predation environments. Our presentation will focus on our
      pilot study, which evaluated life span, lifetime reproduction, and the patterns
      of aging in our laboratory populations. We will also report on the progress in
      our ongoing comparative studies of senescence in natural populations.

PMID- 11295516
TI  - Escaping senescence: demographic data from the three-toed box turtle (Terrapene
      carolina triunguis).
AB  - Two criteria have been proposed for the demonstration of negligible senescence.
      These include (1) no increase in age-related mortality and (2) negligible
      functional impairments with age. Although researchers have suspected turtles to
      exhibit negligible senescence, this has been largely based on the former rather
      than the latter criteria for which scant evidence is available. Using a long-term
      study on a population of three-toed box turtles (Terrapene carolina triunguis) in
      Cole County, Missouri, I combine known minimum age ranges and reproductive
      evidence to demonstrate their apparent escape from senescence. During 1998 and
      1999, eight females >60 years of age were found gravid. The oldest of these is
      estimated to be at least 65-74 years of age. Of females >60 years, the mean
      clutch size and the proportion gravid were greater, although not significantly
      different, when compared to females <60 years. These findings indicate that the
      reproductive function in these turtles does not become impaired with age, thus
      supporting the second criteria for demonstrating negligible senescence.

PMID- 11295515
TI  - Hypotheses of aging in a long-lived vertebrate, Blanding's turtle (Emydoidea
      blandingii).
AB  - For 35 of the past 47 years, Blanding's turtles were studied on the University of
      Michigan's E.S. George Reserve in southeastern Michigan. Blanding's turtle is one
      of the longest-lived emydid turtles with individuals reaching ages greater than
      75 years. We compared body sizes, reproductive traits and survival of Young,
      Middle, and Oldest age groups of Blanding's turtles to test predictions from two
      contrasting hypotheses of aging. The relative reproductive rate hypothesis
      predicts traits that increase the reproductive output or survival rates of older
      compared to younger individuals, whereas the senescence hypothesis predicts a
      reduction in reproductive output or survival in older versus younger individuals.
      Body size did not increase with age among groups; therefore, indeterminate growth
      was not a mechanism for increased reproductive output of the oldest individuals.
      Survivorship, reproductive frequency and size-adjusted mean clutch size were all
      higher in the Oldest age group compared to the younger age groups. Nest predation
      rate was highest in the Young age group compared to either group of older
      turtles. In nests that survived predation, the proportion of nests that failed
      entirely due to developmental problems was lowest in the Young, intermediate in
      the Middle, and highest in the Oldest age group. Successful nests produced
      similar numbers of hatchlings and similar sized hatchlings in all three age
      groups. Traits such as egg and offspring size, and offspring produced per nest
      did not support either the relative reproductive rate or the senescence
      hypothesis of aging. Increased embryo mortality in nests of older females
      compared to younger turtles supports predictions from the senescence hypothesis.
      Three traits; increased clutch size, reproductive frequency, and survivorship of
      individuals in the Oldest age group compared to younger turtles support the
      relative reproductive rate hypothesis for evolution of longevity.

PMID- 11295517
TI  - Detecting and measuring senescence in wild birds: experience with long-lived
      seabirds.
AB  - This paper points out and discusses several practical and methodological problems
      that arise in attempts to detect and measure senescent declines in survival or
      breeding performance of wild animals, with specific emphasis on long-lived
      seabirds. Birds have no anatomical markers of age, so studies of age-related
      biology require marking individuals at the time of hatching and following them
      throughout their lives. Seabirds live longer than the working lifespan of
      biologists, and longer than the turnover times of study techniques or theories of
      senescence. Seabirds are exposed to changing environmental and demographic
      conditions and cannot be assumed to be in demographic equilibrium. Sample sizes
      of the oldest age-classes are always small, requiring either marking very large
      numbers of birds at hatching or continuing studies of old birds over many years.
      Incomplete sampling requires the use of mark-recapture models that have only been
      developed in the last 20years. Mortality selection resulting from demographic
      heterogeneity (selective survival of high-quality individuals) can offset or
      confound the effects of senescent changes within individuals. Many of these
      problems are amenable to solution and will be probably solved within a few years.
      In the meantime, this paper recommends that reviewers should be cautious about
      accepting published reports of senescent declines in natural populations.

PMID- 11295518
TI  - Comparison of aging-related mortality among birds and mammals.
AB  - We use the Weibull model to characterize initial (extrinsic) mortality rates
      (m(0)) and rate of increase in mortality with age (omega) for natural and captive
      populations of birds and mammals. Weibull parameters can be estimated for small
      samples of ages at death by constructing survival curves and fitting the Weibull
      model by nonlinear least-squares regression. Both m(0) and omega decrease in
      captivity, on average, and omega bears a strong relationship to m(0), as it does
      in nature, irrespective of body mass or differences between birds and mammals.
      Rate of aging is most closely related to brain size in birds and to rate of
      postnatal growth in mammals. It is not related to duration of embryonic
      development, body size independently of brain size, or genome size. We suggest
      that causes of extrinsic mortality in nature may be replaced in captivity by
      intrinsically controlled causes of mortality related to processes that regulate
      the rate of aging.

PMID- 11295519
TI  - Quail and other short-lived birds.
AB  - Japanese quail are small galliforms that are migratory and generally live 2 to
      3years in the wild. Although there is evidence for other environmental cues, they
      primarily respond to long daylength for regulation of reproduction. In contrast
      to the Common Tern, a long-lived sea bird that shows little evidence of
      reproductive aging, Japanese quail follow a well-defined process of aging with
      evidence of declining function in reproductive, metabolic, and sensory systems.
      Our studies focus on neuroendocrine changes associated with reproductive aging in
      the Japanese quail, with emphasis on the male in order to study both endocrine
      and behavioral components of reproduction and the process of reproductive aging.

PMID- 11295520
TI  - Comparative biology of aging in birds: an update.
AB  - The long life spans and slow aging rates of birds relative to mammals are
      paradoxical in view of birds' high metabolic rates, body temperatures and blood
      glucose levels, all of which are predicted to be liabilities by current
      biochemical theories of aging. Available avian life-table data show that most
      birds undergo rapid to slow "gradual" senescence. Some seabird species exhibit
      extremely slow age-related declines in both survival and reproductive output, and
      even increase reproductive success as they get older. Slow avian senescence is
      thought to be coupled evolutionarily with delayed maturity and low annual
      fecundity. Recent research in our lab and others supports the hypothesis that
      birds have special adaptations for preventing age-related tissue damage caused by
      reactive oxygen species (ROS) and advanced glycosylation endproducts, or AGEs, as
      well as an unusual capacity for neurogeneration in brain. Much of this work is in
      its early stages, however, and reliable biomarkers for comparing avian and
      mammalian aging need more thorough development.

PMID- 11295521
TI  - Mortality and health in human life spans.
AB  - This paper clarifies the relationship between mortality and morbidity in older
      human populations by addressing two questions. Do mortality and morbidity change
      over time in the same way? Are the age patterns of mortality and morbidity
      similar at the oldest ages? We find that the mortality and morbidity do not
      necessarily change in the same way and that the age patterns of mortality and
      morbidity are not the same. Factors responsible for this include population
      heterogeneity and selectivity, the underlying causes of mortality and morbidity,
      and the mechanisms causing change in mortality and morbidity.

PMID- 11295522
TI  - A new biodemographic model to explain the trajectory of mortality.
AB  - Since Buffon's time (1749), biologists and demographers have repeatedly stated
      that a man in good health will live to be 90, 100 or 110 years old but not
      longer. For demographers, mortality measures essentially the current conditions:
      the quality of the ecological and social environment. For biologists, mortality
      measures mainly the ageing process. Can a biodemographic approach measure the
      current conditions (i.e. the quality of the environment) and the ageing schedule
      together, taking into account that human beings spend the greater part of their
      time improving the quality of their physical and social environment, making it
      more and more favourable to the realisation of their potential longevity? I
      propose two measures of the quality of this environment: first at the age when
      individuals (in average by cohort), in the course of their development, are the
      most robust and the most resistant to environmental hazards, indicated by the
      lowest mortality rate recorded; second at the age when individuals (in average by
      cohort) become frail because of the passage of time, with no or extremely little
      resistance to environmental hazards, indicated by a constant mortality rate among
      the oldest old. Between these two measures of the quality of the environment,
      mortality measures the ageing process leading young vigorous individuals into
      frail senile elders.

PMID- 11295523
TI  - Supercentenarians: slower ageing individuals or senile elderly?
AB  - Although the increase in the number of centenarians is well documented today, at
      least in some countries, this is still not the case for people having reached the
      age of 110 years or more: the supercentenarians. The supercentenarians emerged in
      the mid-1960s. Their numbers have regularly increased since the mid-1970s. The
      current prevalence of known supercentenarians in countries involved in the
      database is approximately five to six times more than in the mid-1970s. In
      roughly 20 years the maximum age observed has increased by about 10 years from
      112 to 122 years. The annual probability of death at age 110 is as low as 0.52
      with the validated data (n=106) or with the exhaustive and validated data (n=73).
      The probabilities of death stagnate between 110 and 115 years, and all the
      computed probabilities fall below the ceiling of 0.6. Our results are compatible
      with the last extrapolations of mortality trajectories using a logistic or a
      quadratic model.

PMID- 11295524
TI  - Antioxidant capacity of mononitrosyl-iron-dithiocarbamate complexes: implications
      for NO trapping.
AB  - Using EPR spectroscopy, we show that the water-soluble mononitrosyl iron
      complexes with N-methyl-D-glucamine dithiocarbamate (MNIC-MGD) ligands can easily
      react with superoxide and with peroxynitrite. The reaction with superoxide
      transforms the paramagnetic MNIC-MGD complex into an EPR silent complex with a
      reaction rate of 3 x 10(7) (M.s)(-1). Suppletion of ascorbate partially restores
      the complexes to their original paramagnetic state. We propose that the reaction
      of MNIC-MGD with either superoxide or peroxynitrite leads to identical EPR silent
      complexes. Our results have important implications for the technique of NO
      trapping in biosystems with Fe-dithiocarbamate complexes, where mononitrosyl-iron
      complexes (hydrophilic as well as hydrophobic) are formed as adducts in the
      trapping reaction. This principle is illustrated by NO trapping experiments on
      viable cultured endothelial cells. We find that MNIC-MGD acts as a very potent
      and water-soluble antioxidant with an efficiency exceeding most SOD mimics.
      Moreover, by accounting for the EPR silent fraction of iron complexes, the
      sensitivity of NO trapping can be enhanced considerably. The method was
      demonstrated for hydrophobic iron-dithiocarbamate complexes in endothelial cell
      cultures, where sensitivity for NO detection was enhanced by a factor of 5.

PMID- 11295525
TI  - Phospholipid hydroperoxide glutathione peroxidase protects against singlet oxygen
      induced cell damage of photodynamic therapy.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PhGPx) is an important enzyme
      in the removal of lipid hydroperoxides (LOOHs) from cell membranes. Cancer
      treatments such as photodynamic therapy (PDT) induce lipid peroxidation in cells
      as a detrimental action. The photosensitizers used produce reactive oxygen
      species such as singlet oxygen ((1)O(2)). Because singlet oxygen introduces lipid
      hydroperoxides into cell membranes, we hypothesized that PhGPx would provide
      protection against the oxidative stress of singlet oxygen and therefore could
      interfere with cancer treatment. To test this hypothesis, human breast cancer
      cells (MCF-7) were stably transfected with PhGPx cDNA. Four clones with varying
      levels of PhGPx activity were isolated. The activities of other cellular
      antioxidant enzymes were not influenced by the overexpression of PhGPx. Cellular
      PhGPx activity had a remarkable inverse linear correlation to the removal of
      lipid hydroperoxides in living cells (r = -0.85), and correlated positively with
      cell survival after singlet oxygen exposure (r = 0.94). These data demonstrate
      that PhGPx provides significant protection against singlet oxygen-generated lipid
      peroxidation via removal of LOOH and suggest that LOOHs are major mediators in
      this cell injury process. Thus, PhGPx activity could contribute to the resistance
      of tumor cells to PDT.

PMID- 11295526
TI  - Effects of aging on the susceptibility to the toxic effects of cyclosporin A in
      rats. Changes in liver glutathione and antioxidant enzymes.
AB  - Free radicals are involved in aging and cyclosporin A-induced toxicity. The age
      related changes in the liver oxidative status of glutathione, lipid peroxidation,
      and the activity of the enzymatic antioxidant defense system, as well as the
      influence of aging on the susceptibility to the hepatotoxic effects of
      cyclosporin (CyA) were investigated in rats of different ages (1, 2, 4, and 24
      months). The hepatic content of reduced glutathione (GSH) increased with aging,
      peaked at 4 months, and decreased in senescent rats. By contrast, glutathione
      disulfide (GSSG) and thiobarbituric acid-reactive substances (TBARS)
      concentrations and superoxide dismutase, catalase, and glutathione peroxidase
      activities were higher in the oldest than in the youngest rats. CyA treatment,
      besides inducing the well-known cholestatic syndrome, increased liver GSSG and
      TBARS contents and the GSSG/GSH molar ratio, and altered the nonenzymatic and
      enzymatic antioxidant defense systems. The CyA-induced cholestasis and hepatic
      depletion of GSH, and the increases in the GSSG/GSH ratio, and in GSSG and TBARS
      concentrations were higher in the older than the mature rats. Moreover,
      superoxide dismutase and catalase activities were found to be significantly
      decreased only in treated senescent rats. The higher CyA-induced oxidative
      stress, lipoperoxidation, and decreases in the antioxidant defense systems in the
      aged animals render them more susceptible to the hepatotoxic effects of
      cyclosporin.

PMID- 11295528
TI  - Biological aging does not lead to the accumulation of oxidized Cu,Zn-superoxide
      dismutase in the liver of F344 rats.
AB  - Cu,Zn-Superoxide dismutase (SOD) was isolated from the liver of 3-, 12-, and 26
      month-old Fisher 344 (F344) rats. Specific activity and metal content of the
      enzyme, purified by ion-exchange and size-exclusion chromatography, did not
      significantly change with age. Electrospray ionization-mass spectrometry and
      amino acid analysis of Cu,Zn-SOD apoprotein, further purified by reverse-phase
      HPLC, showed neither significant loss of amino acids nor accumulation of oxidized
      isoforms with age. When bovine Cu,Zn-SOD, oxidized with H(2)O(2) in vitro, was
      added to rat liver homogenate, we reisolated circa 70% of the oxidized bovine
      Cu,Zn-SOD together with the rat isoform, showing that oxidized Cu,Zn-SOD can be
      recovered from tissue homogenate. Therefore, our data do not confirm an earlier
      hypothesis that oxidatively modified Cu,Zn-SOD protein accumulates in the liver
      of aged F344 rats.

PMID- 11295527
TI  - Aldehydes potentiate alpha(2)(I) collagen gene activity by JNK in hepatic
      stellate cells.
AB  - Hepatic stellate cells (HSCs) are responsible for type I collagen deposition in
      liver fibrosis that leads to cirrhosis. The purpose of this study was to examine
      potential molecular signals that lead to increased alpha(2)(I) collagen gene
      expression by acetaldehyde, the primary metabolite of alcohol and malondialdehyde
      (MDA), a lipid peroxidation product known to be associated with chronic liver
      injury. MDA and the combination of MDA and acetaldehyde were employed to
      determine the effect on alpha(2)(I) collagen gene expression as assessed by
      transient transfection analysis and reverse transcriptase polymerase chain
      reaction (RT-PCR). Immunoblot and subsequent immunoprecipitation analysis
      examined stress-activated protein kinase (SAPK) activity. Cotransfection with a
      dominant negative mutant for c-jun nuclear kinase (dnJNK1) was also employed with
      the alpha(2)(I) collagen promoter. MDA increased alpha(2)(I) collagen gene
      expression nearly 2.5- to 3-fold, however there was no synergistic effect of the
      combination of acetaldehyde and MDA on alpha(2)(I) collagen gene activation and
      expression. Acetaldehyde, MDA, or both significantly increased JNK activity when
      compared to untreated stellate cells. The dnJNK1 expression vector abrogated
      alpha(2)(I) collagen transgene activity. In conclusion, JNK activation appears to
      be critical in the signaling cascade of oxidative metabolites of chronic alcohol
      related liver injury and collagen gene activation.

PMID- 11295529
TI  - Effects of tocopheryl quinone on the heart: model experiments with xanthine
      oxidase, heart mitochondria, and isolated perfused rat hearts.
AB  - It is generally accepted that the protection effect of biological tissues by
      vitamin E is due to its radical scavenging potency in membranes, thereby being
      transformed to a vitamin E radical. A deficiency of appropriate reductants, which
      recycle vitamin E radicals back to its antioxidative active form, causes an
      irreversible degradation of vitamin E leading to tocopheryl quinone (TQ). TQ-like
      compounds were shown to result from both vitamin E and corresponding hydrophilic
      analogues of this antioxidant in vitro. In vivo elevated concentrations of
      tocopheryl quinones were detected after oxidative stress and TQ supplementation
      as well. Quinones in general are known to be efficient one-electron donors and
      acceptors. Therefore the question arises whether TQ-like compounds can undergo
      redox-cycling in conjunction with redox-active enzymes in the heart, thereby
      producing harmful oxygen radicals, or whether these compounds exhibit antioxidant
      properties. In order to elucidate this question we focused our interest on the
      interaction of TQ and a corresponding short-chain homologue (TQ(0)) with xanthine
      oxidase and heart mitochondria. Furthermore, we tested the influence of TQ on the
      recovery of isolated perfused rat hearts after ischemia/reperfusion. Our
      experiments revealed that hydrophilic TQ(0) was univalently reduced by xanthine
      oxidase (XOD) yielding semiquinone radicals in the absence of oxygen. However,
      under aerobic conditions TQ(0) enhanced the O(2)(*)(-) radical output of XOD. In
      the mitochondrial respiratory chain TQ was shown to interact with high potential
      cytochrome b in the bc(1) complex specifically. In contrast to the system
      XOD/TQ(0), lipophilic TQ in submitochondrial particles decreased the O(2)(*)(-)
      radical release during regular respiration possibly due to its interaction with b
      cytochromes in the mitochondrial respiratory chain. In isolated rat hearts
      perfused with liposomes containing lipophilic TQ, it was efficiently accumulated
      in the heart tissue. When hearts were subjected to conditions of
      ischemia/reperfusion, infusion of TQ prior to ischemia significantly improved the
      recovery of hemodynamic parameters. Our results demonstrate that TQ derivatives
      may induce pro-oxidative and antioxidative effects depending on the distribution
      of TQ derivatives in the heart tissue and the interacting redox system.

PMID- 11295530
TI  - Beneficial effects of astringinin, a resveratrol analogue, on the ischemia and
      reperfusion damage in rat heart.
AB  - Oxidative stress plays an important role in the pathogenesis of myocardial
      ischemia and infarction. Antioxidants might then be beneficial in the prevention
      of these diseases. Astringinin (3,3',4',5-tetrahydroxystilbene), a resveratrol
      (3,4',5-trihydroxystilbene) analogue with considerably higher antioxidative
      activity and free radical scavenging capacity, was introduced to examine its
      cardioprotective effects in ischemia or ischemia-reperfusion (I/R) rats. In the
      present study, the left main coronary artery was occluded by the following
      procedures: (i) 30 min occlusion, (ii) 5 min occlusion followed by 30 min
      reperfusion, and (iii) 4 h occlusion. Animals were infused with and without
      astringinin before coronary artery occlusion. Mortality, and the severity of
      ischemia- and I/R-induced arrhythmias were compared. Pretreatment of astringinin
      dramatically reduced the incidence and duration of ventricular tachycardia (VT)
      and ventricular fibrillation (VF) during either ischemia or I/R period.
      Astringinin at 2.5 x 10(-5) and 2.5 x 10(-4) g/kg completely prevented the
      mortality of animals during ischemia or I/R. During the same period, astringinin
      pretreatment also increased nitric oxide (NO) and decreased lactate dehydrogenase
      (LDH) levels in the carotid blood. In animals subjected to 4 h coronary
      occlusion, the cardiac infarct size (expressed as a percentage of occluded zone)
      was reduced from 44.4 + or - 4.1% to 19.1 + or - 2.4% by astringinin (2.5 x 10(
      4) g/kg). We conclude that, astringinin is a potent antiarrhythmic agent with
      cardioprotective activity in ischemic and ischemic-reperfused rat heart. The
      beneficial effects of astringinin in the ischemic and ischemic-reperfused hearts
      may be correlated with its antioxidant activity and upregulation of NO
      production.

PMID- 11295531
TI  - Apoptosis in RAW 264.7 cells exposed to 4-hydroxy-2-nonenal: dependence on
      cytochrome C release but not p53 accumulation.
AB  - The toxic reactive aldehyde lipid peroxidation byproduct 4-hydroxy-2-nonenal
      (HNE) is thought to be a major contributor to oxidant stress-mediated cell
      injury. HNE induced apoptosis in RAW 264.7 murine macrophage cells in a dose
      dependent manner within 6-8 h after exposure. Expression of the antiapoptotic
      protein Bcl-2 in stably transfected RAW 264.7 cells prevented HNE-induced
      internucleosomal DNA fragmentation and apoptosis, and these cells resume growth
      after a temporary (24-48 h) growth delay. While parental RAW 264.7 cells released
      mitochondrial cytochrome c within 3 h after HNE exposure, expression of Bcl-2
      prevented cytochrome c release. In control cells, p53 protein levels peaked at 6
      9 h after HNE exposure and then declined, while in Bcl-2 expressing cells, p53
      levels were maximal at 6-9 h and remained elevated up to 96 h. Expression of SV40
      large T-antigen, which forms a stable complex with p53 protein, via stable
      transfection-blocked transactivation of the p53-regulated gene p21(WAF1/CIP1),
      but did not affect induction of apoptosis by HNE, suggesting that p53 function is
      not important in HNE-induced apoptosis. These results suggest that cytochrome c
      release, but not p53 accumulation, plays an essential role in HNE-induced
      apoptosis in RAW 264.7 cells.

PMID- 11295532
TI  - Dual regulation of glutathione peroxidase by docosahexaenoic acid in endothelial
      cells depending on concentration and vascular bed origin.
AB  - Docosahexaenoic acid (DHA) has been reported to elicit oxidative stress, which in
      turn can induce antioxidant enzymes. Glutathione peroxidase (GPx) has received
      particular attention in this respect, as this enzyme is specifically required for
      the degradation of lipid hydroperoxides. Because we previously found that DHA
      could protect against oxidative stress when used in low amounts, we have compared
      the effect of a low (10 microM) versus high (100 microM) concentration of DHA on
      oxidant/antioxidant balance in bovine retinal and bovine aortic endothelial cells
      (BREC and BAEC). At 100 microM, DHA elicited a marked oxidative stress, as
      evidenced by high malondialdehyde levels and decreased plasmalogen
      phosphatidylethanolamine in both cells, and for BAEC only, a decrease of alpha
      tocopherol. At 10 microM, DHA induced a slight increase of malondialdehyde in
      both cells, but did not affect alpha-tocopherol levels, which is indicative of a
      mild oxidative stress. In BREC, 10 microM DHA slightly but significantly
      decreased cytosolic GPx (cGPx) activity whereas 100 microM had no effect. In
      contrast, in BAEC, DHA 10 microM did not affect cGPx activity, whereas 100 microM
      increased it. The decreased cGPx activity in BREC was associated with a lower
      level of protein, suggesting a transcriptional and/or posttranscriptional effect.
      Phospholipid hydroperoxide GPx (PHGPx) activity was not modified by DHA at either
      concentration in BREC, whereas it was increased in BAEC when using 100 microM.
      Our results confirm that large amounts of DHA lead to oxidative stress, but do no
      support an antioxidant action of DHA at low concentration, in endothelium.
      Nevertheless, we showed that DHA can exert opposite effects on GPx regulation in
      endothelial cells, with regard to its concentration and to vascular bed origin.

PMID- 11295533
TI  - Oxidative damages are critical in pathogenesis of reflux esophagitis: implication
      of antioxidants in its treatment.
AB  - BACKGROUND: The facts that the severity of reflux esophagitis cannot be
      accurately predicted on the basis of acid exposure and acid suppression treatment
      is not enough for the complete healing, suggested that other damaging factors
      might be involved in pathogenesis of reflux esophagitis. AIMS: The present study
      was designed to evaluate the oxidative stress as the major pathogenic factor of
      reflux esophagitis and the importance of antioxidant in treatment of reflux
      esophagitis. MATERIALS AND METHODS: Reflux esophagitis was induced by the
      insertion of small caliber ring (3 mm in diameter) into the duodenum 1 cm distal
      to the ligament of Treitz in rats. RESULTS: DA-9601, a novel antioxidant
      substance, attenuated the gross esophagitis significantly compared to that
      treated with ranitidine, histamine-2 receptor antagonist (H2-RA), in a dose
      dependent manner. Severe, hemorrhagic, and longitudinal ulcerations were
      developed in H2-RA pretreated group, whereas mildly scattered erosions were
      observed in antioxidant-pretreated group. Significantly increased amounts of
      malondialdehyde (MDA), increased NF-kappaB activation, and the mucosal depletion
      of reduced glutathione (GSH) were observed in the esophagus of reflux
      esophagitis. H2-RA treatment didn't affect the levels of GSH and MDA, whereas DA
      9601 attenuated the decrement of the GSH levels and significantly decreased lipid
      peroxides in the esophagus. Antioxidants treatment showed significant reductions
      in the activation of NF-kappaB, inflammation-associated transcription factor,
      especially p50 component in accordance with significant higher levels of NF
      kappaB repressor, IkappaBalpha expression. CONCLUSION: Oxygen-derived free
      radicals seem to be one of the important mediators in generation of reflux
      esophagitis, which suggests that the combination of antioxidant and anti
      secretory medications will be ideal and more beneficial in the prevention and
      treatment of reflux esophagitis than currently prescribed antisecretory treatment
      alone.

PMID- 11295534
TI  - DNA repair and aging in mouse liver: 8-oxodG glycosylase activity increase in
      mitochondrial but not in nuclear extracts.
AB  - 8-oxo-deoxyguanosine (8-oxodG) is one of the major DNA lesions formed upon
      oxidative attack of DNA. It is a mutagenic adduct that has been associated with
      pathological states such as cancer and aging. Base excision repair (BER) is the
      main pathway for the repair of 8-oxodG. There is a great deal of interest in the
      question about age-associated accumulation of this DNA lesion and its
      intracellular distribution, particularly with respect to mitochondrial or nuclear
      localization. We have previously shown that 8-oxodG-incision activity increases
      with age in rat mitochondria obtained from both liver and heart. In this study,
      we have investigated the age-associated changes in DNA repair activities in both
      mitochondrial and nuclear extracts obtained from mouse liver. We observed that 8
      oxodG incision activity of mitochondrial extracts increases significantly with
      age, from 13.4 + or - 2.2 fmoles of oligomer/100 microg of protein/16 h at 6 to
      18.6 + or - 4.9 at 14 and 23.7 + or - 3.8 at 23 months of age. In contrast, the
      nuclear 8-oxodG incision activity showed no significant change with age, and in
      fact slightly decreased from 11.8 + or - 3 fmoles/50 microg of protein/2 h at 6
      months to 9.7 + or - 0.8 at 14 months. Uracil DNA glycosylase and endonuclease G
      activities did not change with age in nucleus or mitochondria. Our results show
      that the repair of 8-oxodG is regulated differently in nucleus and mitochondria
      during the aging process. The specific increase in 8-oxodG-incision activity in
      mitochondria, rather than a general up-regulation of DNA metabolizing enzymes in
      those organelles, suggests that this pathway may be up regulated during aging in
      mice.

PMID- 11295536
TI  - Monochloramine inhibits etoposide-induced apoptosis with an increase in DNA
      aberration.
AB  - Monochloramine (NH(2)Cl) is a physiological oxidant produced by activated
      neutrophils, and it affects apoptosis signaling. We studied the effects of
      NH(2)Cl on the cell death induced by etoposide, a widely used anticancer agent
      that is directed to DNA topoisomerase II. Jurkat T cells, a human acute T cell
      leukemia cell line, were pretreated with 70 microM of NH(2)Cl for 10 min. After
      24 h, 5-30 microM of etoposide was added to the NH(2)Cl pretreated and control
      cells, and their apoptosis, caspase activity, cell morphology, and cellular DNA
      contents were measured. NH(2)Cl pretreatment significantly inhibited apoptosis
      and caspase activation induced by etoposide or camptothecin, a DNA topoisomerase
      I poison, but not by staurosporine or Fas stimulation. The apoptosis inhibition
      actually resulted in the proliferation of the survived cells and, notably, the
      survived cells showed more aberrant morphology, such as variation in nuclear
      size, nuclear fragments, and multinucleated cells. DNA content analysis of the
      survived cells showed an increase in aneuploid nuclei. Cell cycle analysis after
      24 h of NH(2)Cl treatment showed a significant decrease in S phase cells with a
      concurrent increase in G(0)/G(1) phase cells, which suggested that NH(2)Cl
      induced G(1) arrest. Using synchronized Jurkat cells, etoposide and camptothecin
      were found to be particularly cytotoxic to S phase cells, whereas staurosporine
      and Fas stimulation were not. Thus NH(2)Cl-induced G(1) arrest was a likely cause
      of the observed resistance to etoposide. These observations suggested that
      inflammation-derived oxidants may make the tumor cells more resistant to
      etoposide and increase the risk of tumor progression and the development of
      secondary tumors by increasing the survival of DNA damage-bearing cells.

PMID- 11295537
TI  - A question of strategy.

PMID- 11295535
TI  - Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets
      mitochondria.
AB  - Parkinson's disease (PD) is a major cause of age-related morbidity and mortality,
      present in nearly 1% of individuals at ages 70-79 and approximately 2.5% of
      individuals at age 85. L-DOPA (L-dihydroxyphenylalanine), which is metabolized to
      dopamine by dopa decarboxylase, is the primary therapy for PD, but may also
      contribute to disease progression. Association between mitochondrial dysfunction,
      monoamine oxidase (MAO) activity, and dopaminergic neurotoxicity has been
      repeatedly observed, but the mechanisms underlying selective dopaminergic neuron
      depletion in aging and neurodegenerative disorders remain unclear. We now report
      that 3,4-dihydroxyphenylacetaldehyde (DOPAL), the MAO metabolite of dopamine, is
      more cytotoxic in neuronally differentiated PC12 cells than dopamine and several
      of its metabolites. In isolated, energetically compromised mitochondria,
      physiological concentrations of DOPAL induced the permeability transition (PT), a
      trigger for cell death. Dopamine was > 1000-fold less potent. PT inhibitors
      protected both mitochondria and cells against DOPAL. Sensitivity to DOPAL was
      reduced > or = 30-fold in fully energized mitochondria, suggesting that
      mitochondrial respiration may increase resistance to PT induction by the
      endogenous DOPAL in the substantia nigra. These data provide a potential
      mechanism of action for L-DOPA-mediated neurotoxicity and suggest two potentially
      interactive mechanisms for the selective vulnerability of neurons exposed to
      dopamine.

PMID- 11295538
TI  - Nitric oxide moves myoglobin centre stage.
AB  - It has been proposed that myoglobin (Mb), besides being an oxygen carrier, plays
      the role of a nitric oxide (NO) scavenger in heart and skeletal muscle. A paper
      reporting data obtained using perfused hearts isolated from either wild-type or
      Mb-knockout mice provides the first experimental evidence for this novel function
      of Mb. The biochemical basis underlying the effects of NO on cardiac function is
      outlined in this article, beginning with the idea that this gas is an inhibitor
      of cytochrome-c oxidase. Some of the consequences of this new role of Mb and a
      molecular mechanism to account for the high reactivity of oxymyoglobin with NO
      are also briefly discussed.

PMID- 11295539
TI  - Transcription factors: bound to activate or repress.
AB  - The complex processes of eukaryotic gene expression are controlled by a
      relatively small number of transcription factors whose activities are modulated
      by a diverse set of regulatory mechanisms. A recent paper describes the molecular
      basis for one such mechanism in which the Pit-1 transcription factor activates or
      represses transcription depending on the sequence of the DNA to which it binds.
      The mechanism by which the binding-site sequence regulates the activity of Pit-1
      is discussed in relation to that of other transcription factors.

PMID- 11295540
TI  - Nicastrin, a presenilin-interacting protein, contains an
      aminopeptidase/transferrin receptor superfamily domain.
AB  - Nicastrin, a protein implicated in Alzheimer's disease, has a domain that is
      found in the aminopeptidase/transferrin receptor superfamily. In nicastrin, this
      domain might possess catalytic activity (as observed with aminopeptidases) or it
      could serve merely as a binding domain (with analogy to the transferrin
      receptors) for the beta-amyloid precursor protein.

PMID- 11295541
TI  - THUMP--a predicted RNA-binding domain shared by 4-thiouridine, pseudouridine
      synthases and RNA methylases.
AB  - Sequence profile searches were used to identify an ancient domain in ThiI-like
      thiouridine synthases, conserved RNA methylases, archaeal pseudouridine synthases
      and several uncharacterized proteins. We predict that this domain is an RNA
      binding domain that adopts an alpha/beta fold similar to that found in the C
      terminal domain of translation initiation factor 3 and ribosomal protein S8.

PMID- 11295542
TI  - Small, but deadly: small-molecule inhibition of Bcl-2 homologue
      heterodimerization.

PMID- 11295543
TI  - YUCCA: a flavin monooxygenase in auxin biosynthesis.

PMID- 11295544
TI  - Branching out: cortactin stabilizes actin networks generated by the Arp2/3
      complex.

PMID- 11295546
TI  - Translational control and synaptic activity: a role for IRES elements?

PMID- 11295547
TI  - Cytohesins and centaurins: mediators of PI 3-kinase regulated Arf signaling.

PMID- 11295554
TI  - Translation control: bridging the gap between genomics and proteomics?
AB  - mRNA profiling enables the expression levels of thousands of transcripts in a
      cell to be monitored simultaneously. Nevertheless, analyses in yeast and
      mammalian cells have demonstrated that mRNA levels alone are unreliable
      indicators of the corresponding protein abundances. This discrepancy between mRNA
      and protein levels argues for the relevance of additional control mechanisms
      besides transcription. As translational control is a major mechanism regulating
      gene expression, the use of translated mRNA in profiling experiments might depict
      the proteome more closely than does the use of total mRNA. This would combine the
      technical potential of genomics with the physiological relevance of proteomics.

PMID- 11295553
TI  - The temperature optima of enzymes: a new perspective on an old phenomenon.
AB  - Careful analysis of the dependence of enzyme activity on assay temperature has
      revealed that some enzymes might have real temperature optima in which the
      decrease in catalytic rate at temperatures above the optimum is not primarily a
      result of irreversible thermal inactivation. The 'equilibrium model' has been
      formulated to describe genuine temperature optima, and to suggest a simple
      experimental method by which to distinguish these cases from those in which
      enzyme instability is the major determinant of temperature optima.

PMID- 11295555
TI  - Recognition of antigens by single-domain antibody fragments: the superfluous
      luxury of paired domains.
AB  - The antigen-binding site of antibodies from vertebrates is formed by combining
      the variable domains of a heavy chain (VH) and a light chain (VL). However,
      antibodies from camels and llamas are an important exception to this in that
      their sera contain, in addition, a unique kind of antibody that is formed by
      heavy chains only. The antigen-binding site of these antibodies consists of one
      single domain, referred to as VHH. This article reviews the mutations and
      structural adaptations that have taken place to reshape a VH of a VH-VL pair into
      a single-domain VHH with retention of a sufficient variability. The VHH has a
      potent antigen-binding capacity and provides the advantage of interacting with
      novel epitopes that are inaccessible to conventional VH-VL pairs.

PMID- 11295556
TI  - Interactions between prion protein isoforms: the kiss of death?
AB  - Direct interactions between the normal and aberrant forms of prion protein appear
      to be crucial in the transmission and pathogenesis of transmissible spongiform
      encephalopathies (TSEs) or prion diseases. Recent studies of such interactions in
      vitro have provided mechanistic insight into how TSE-associated prion protein
      might promote its own propagation in a manner that is specific enough to account,
      at least in part, for TSE strains and species barriers.

PMID- 11295557
TI  - Actin-based motility: stop and go with Ena/VASP proteins.
AB  - Proteins of the Ena/VASP (Enabled/vasodilator-stimulated phosphoprotein) family
      are involved in Abl and/or cyclic nucleotide-dependent protein kinase signaling
      pathways. These proteins are also crucial factors in regulating actin dynamics
      and associated processes such as cell-cell adhesion, platelet function and actin
      based motility of both cytopathogenic Listeria and their eukaryotic host cells.
      Although biochemical mechanisms have emerged depicting Ena/VASP proteins as
      enhancers of actin filament formation, increasing evidence also suggests that
      these proteins have inhibitory functions in integrin regulation, cell motility
      and axon guidance.

PMID- 11295558
TI  - The histone fold is a key structural motif of transcription factor TFIID.
AB  - Transcription factor TFIID is a multiprotein complex composed of the TATA binding
      protein and its associated factors, and is required for accurate and regulated
      initiation of transcription by RNA polymerase II. The subunit composition of this
      factor is highly conserved from yeast to mammals. X-ray crystallography and
      biochemical experiments have shown that the histone fold motif mediates many of
      the subunit interactions within this complex. These results, together with
      electron microscopy and yeast genetics, provide insights into the overall
      organization of this complex.

PMID- 11295560
TI  - GEFs: master regulators of G-protein activation.

PMID- 11295561
TI  - The advent of genetic engineering.

PMID- 11295559
TI  - Transmembrane signaling in bacterial chemoreceptors.
AB  - Bacterial chemoreceptors mediate chemotaxis by recognizing specific chemicals and
      regulating a noncovalently associated histidine kinase. Ligand binding to the
      external domain of the membrane-spanning receptor generates a transmembrane
      signal that modulates kinase activity inside the cell. This transmembrane
      signaling is being investigated by novel strategies, which have revealed a
      remarkably subtle conformational signal carried by a signaling helix that spans
      the entire length of the >350-A-long receptor. Multiple, independent lines of
      evidence indicate that, in the periplasmic and transmembrane domains,
      conformational signaling is a piston-type sliding of the signaling helix towards
      the cytoplasm.

PMID- 11295562
TI  - Type 2 diabetes mellitus and worm longevity: a transcriptional link to cure?
AB  - In Caenorhabditis elegans, an insulin-like signalling pathway culminates in a
      transcription factor (TF) that is homologous to a subfamily of TFs responsible
      for the regulation of a subset of insulin-responsive genes in humans. Under harsh
      conditions, C. elegans reduces signalling through this pathway and arrests
      developmentally in a manner that is similar to the metabolic syndrome of humans.
      We propose that an understanding of this pathway could lead to drugs with optimal
      potency and selectivity in the treatment of type 2 diabetes mellitus.

PMID- 11295563
TI  - K cells: a novel target for insulin gene therapy for the prevention of diabetes.
AB  - Recently, gut K cells have been shown to express glucokinase, the glucose sensor
      of pancreatic beta cells, and transgenic mice expressing human insulin under the
      control of a K cell-specific promoter are resistant to diabetes development
      induced by the beta-cell toxin streptozotocin. These novel findings suggest that
      gut K cells might be a suitable target for gene therapeutic treatment of type 1
      diabetes mellitus.

PMID- 11295564
TI  - An apple a day keeps diabetes away.

PMID- 11295565
TI  - PCOS and an increased risk of type 2 diabetes mellitus.

PMID- 11295566
TI  - Bone loss prevention by an antimalarial drug.

PMID- 11295567
TI  - Distinguishing prostate cancer from BPH.

PMID- 11295568
TI  - Treatment of luteal phase defect by ovarian stimulation.

PMID- 11295569
TI  - Regulation of angiogenesis in the endometrium.
AB  - A crucial stage in pregnancy is the implantation of the embryo into the
      endometrium. The endometrium, which is situated in the lining of the uterus, is a
      complex structure consisting of a single epithelial layer overlying a mesenchymal
      stroma. Cyclical growth of the endometrium under the influence of ovarian
      steroids results in the establishment of a receptive endometrium. If implantation
      fails, or is deliberately prevented by the use of fertility regulation, the
      endometrium is shed by the process of menstruation. This unique system of cyclic
      tissue regeneration is dependent on the cyclical growth and regression of the
      blood vessels that supply the endometrium. Little attention has been paid to this
      crucial aspect of human reproduction but it now appears that many disorders that
      reduce the quality of life of modern women, such as heavy menstruation,
      endometriosis, breakthrough bleeding and infertility, might have their basis in
      disorders of the endometrial vasculature.

PMID- 11295570
TI  - Rapid actions of plasma membrane estrogen receptors.
AB  - Functional evidence for the existence of plasma membrane estrogen receptors in a
      variety of cell types continues to accumulate. Many of these functions originate
      from rapid signaling events, transduced in response to 17beta-estradiol (E(2)).
      It has been convincingly shown that E(2) activates phosphoinositol 3-kinase and
      protein kinase B/AKT, and stimulates ERK and p38 MAP kinases. In part, this stems
      from G-protein activation and the resulting calcium flux. As a result, the link
      between E(2) action at the cell membrane and discrete biological actions in the
      cell has been strengthened. There is now convincing in vitro evidence that E(2)
      can modulate the functions of neural and vascular cells via non-genomic actions.
      Thus, the actions of discrete pools of E(2) receptors are likely to contribute to
      the overall effects of the sex steroids.

PMID- 11295571
TI  - Angiotensin III: a central regulator of vasopressin release and blood pressure.
AB  - Among the main bioactive peptides of the brain renin-angiotensin system,
      angiotensin (Ang) II and AngIII exhibit the same affinity for type 1 and type 2
      AngII receptors. Both peptides, injected intracerebroventricularly, cause similar
      increases in vasopressin release and blood pressure. Because AngII is converted
      in vivo to AngIII, the identity of the true effector is unknown. This review
      summarizes new insights into the predominant role of brain AngIII in the control
      of vasopressin release and blood pressure and underlines the fact that brain
      aminopeptidase A, the enzyme forming central AngIII, could constitute a putative
      central therapeutic target for the treatment of hypertension.

PMID- 11295572
TI  - Genes governing placental development.
AB  - The placenta is essential for fetal growth because it promotes the delivery of
      nutrients and oxygen from the maternal circulation. In mice, many gene mutations
      disrupt formation of the placenta, with specific effects at different times and
      on different components. Studies of these mutations are beginning to provide
      insights into both the molecular pathways required for formation of different
      placental substructures and the nature of intercellular interactions, between
      trophoblast, mesenchymal and vascular components, that regulate placental
      development. Conserved gene expression patterns in humans should enable the
      elucidation of the molecular basis of human placental dysfunction.

PMID- 11295573
TI  - Is there an astrocyte-neuron ketone body shuttle?
AB  - Ketone bodies can replace glucose as the major source of brain energy when
      glucose becomes scarce. Although it is generally assumed that the liver supplies
      extrahepatic tissues with ketone bodies, recent evidence shows that astrocytes
      are also ketogenic cells. Moreover, the partitioning of fatty acids between
      ketogenesis and ceramide synthesis de novo might control the survival/death
      decision of neural cells. These findings support the notion that astrocytes might
      supply neurons with ketone bodies in situ, and raise the possibility that
      astrocyte ketogenesis is a cytoprotective pathway.

PMID- 11295574
TI  - Multiple endocrine neoplasia type 1: new clinical and basic findings.
AB  - Multiple endocrine neoplasia type 1 (MEN1) provides a prime example of how a rare
      disease can advance our understanding of basic cell biology, neoplasia and common
      endocrine tumors. MEN1 is expressed mainly as parathyroid, enteropancreatic
      neuroendocrine, anterior pituitary and foregut carcinoid tumors. It is an
      autosomal dominant disease caused by mutation of the MEN1 gene. Since its
      identification, the MEN1 gene has been implicated in many common endocrine and
      non-endocrine tumors. This is a brief overview of recent scientific advances
      relating to MEN1, including newly recognized clinical features that are now
      better characterized by genetic analysis, insights into the function of the MEN1
      encoded protein menin, and refined recommendations for mutation testing and tumor
      screening, which highlight our increasing understanding of this complex syndrome.

PMID- 11295575
TI  - Role of vascular remodeling in the pathogenesis of early transplant coronary
      artery disease: a multicenter prospective intravascular ultrasound study.
AB  - BACKGROUND: Luminal narrowing in transplant coronary artery disease is thought to
      be primarily caused by intimal proliferation, and the role of vascular remodeling
      is less certain. METHODS AND RESULTS: We studied cardiac allografts from 83
      prospectively recruited patients immediately and 1 year after transplant using
      intravascular ultrasound in a multicenter study. We measured coronary artery
      dimensions in 310 angiographically matched segments (175 were also fully matched
      by ultrasound criteria). At 1 year, lumen area changed by -1.8 +/- 3.7 mm(2) (p <
      0.0001, 14% of baseline lumen area). Thirty-three percent of this luminal loss
      was due to intimal thickening and 67% to vessel shrinkage. Shrinkage also
      occurred (-0.9 +/- 3.2 mm(2), 7% of baseline total area) in segments free of
      detectable intimal disease at baseline and at 1 year. Using the mean baseline
      total vessel area (13.9 mm(2)) as the cutoff, we divided the cohort into the
      large and the small coronary-segment groups. The large-segment group (n = 176)
      shrank more (-2.6 +/- 4.4 vs. -0.03 +/- 2.8 mm(2), p < 0.0001), but intimal
      growth was similar in both groups (0.8 +/- 2.2 vs. 0.4 +/- 1.3 mm(2), p = not
      significant). Analysis of the 175 fully ultrasound matched sub-cohort showed
      similar results. Changes in intimal area, total vessel area, and lumen area were
      similar in segments with (n = 132) and segments without (n = 178) pre-existing
      donor disease. Despite overall shrinkage, change in total vessel area positively
      correlated with change in intimal area (r = 0.29, p < 0.0001). CONCLUSION: In
      large coronary segments, coronary artery shrinkage plays an important role in the
      loss of luminal diameter early after cardiac transplantation, whereas new intimal
      growth occurs in both large and small segments. Pre-existent donor disease does
      not aggravate these processes. Compensatory remodeling with increasing intimal
      growth retards the rate of lumen loss. As is intimal thickening, shrinkage and
      compensatory remodeling are important pathogenic mechanisms in transplant
      coronary artery disease.

PMID- 11295576
TI  - Cellular rejection and rate of progression of transplant vasculopathy: a 3-year
      serial intravascular ultrasound study.
AB  - Intravascular ultrasound (IVUS) is established as the optimal method for early
      detection of transplant vasculopathy. The association between cellular rejection
      and development of transplant vasculopathy remains controversial. This study
      attempts to determine the rate of progression of transplant vasculopathy lesions
      and its relationship with cellular rejection in a long-term (> 1 year) IVUS
      serial follow-up.A study cohort of 47 patients undergoing heart transplantation
      from 1993 to 1995 was evaluated. Intravascular ultrasound was performed at
      baseline (within 8 weeks) and annually for a period of 3 years to determine
      maximum intimal thickness and maximum plaque area in each coronary segment.
      Significant allograft vasculopathy was defined as a site with intimal thickness >
      0.5 mm not present at baseline. Biopsy results were scored by assigning a
      numerical weight to each ISHLT grade during the first year. Donor lesions ranged
      from 0.86 to 1.1 mm, showing no evidence of progression at serial follow-up. De
      novo lesions were identified in 30 patients. These lesions appeared yearly but
      progressed slowly. The average biopsy score in the entire cohort was 1.1 +/- 0.8.
      Average biopsy score was > 1.0 in 35 patients with significant linear correlation
      between the rate of intimal progression and biopsy score (r = 0.42, p = 0.01).
      Multivariate analysis demonstrated that only the biopsy score correlated with the
      rate of progression. Lesions of donor atherosclerosis do not change significantly
      after transplantation. However, de novo lesions continue to develop every year.
      In patients with evidence of rejection, the rate of progression of transplant
      vasculopathy correlates with the severity of rejection.

PMID- 11295577
TI  - Impact of heart transplantation on the safety and feasibility of the dobutamine
      stress test.
AB  - BACKGROUND: Dobutamine myocardial perfusion imaging is a useful method for
      evaluation of coronary artery disease. However, this technique does not allow for
      ischemia monitoring, which may have an impact on the safety of the test in heart
      transplant recipients due to cardiac sensory denervation. The aim of this study
      was to assess the impact of heart transplantation on the feasibility and
      complications of the dobutamine stress test. METHODS: We studied 225 heart
      transplant recipients (mean age 57 +/- 7 years) and a control group of 225
      patients without previous transplant matched for age and gender by dobutamine (up
      to 40 microg/kg per minute) stress myocardial perfusion imaging. RESULTS: During
      the test, transplant recipients had a lower prevalence of premature ventricular
      contractions (23% vs. 37%, p < 0.001) and ventricular tachycardia (0.04% vs 7.5%,
      p < 0.0001) compared with control patients. By multivariate analysis, heart
      transplantation was a powerful independent variable associated with a reduced
      risk of ventricular arrhythmias (chi(2) = 20.8, p < 0.0001) and minor side
      effects (nausea, dizziness, anxiety, flushing, chills) (chi(2) = 20, p < 0.0001)
      during dobutamine stress. The target heart rate was reached in 82% of transplant
      recipients and in 77% of the control group. Overall feasibility (achievement of
      the target heart rate and/or an ischemic end-point) was 87% in the transplant and
      86% in the control group. CONCLUSIONS: Dobutamine stress myocardial perfusion
      imaging is a safe and feasible method for evaluation of coronary artery disease
      in heart transplant recipients. The prevalence of arrhythmias and minor
      complications using the dobutamine stress test is lower in heart transplant
      recipients compared with control patients. The independent association between
      heart transplantation and reduced risk of arrhythmias and minor side effects of
      the dobutamine stress test indicates that cardiac sensory and autonomic nerve
      function plays a major role in the induction of these complications during the
      test.

PMID- 11295578
TI  - Differential expression of RANTES chemokine, TGF-beta, and leukocyte phenotype in
      acute cellular rejection and quilty B lesions.
AB  - BACKGROUND: Because of the complexity of the trabeculated endocardial surface and
      tangential histologic sectioning, the differentiation of acute cellular rejection
      (ACR) from Quilty B lesions (QB) in endomyocardial biopsies (EMBs) is
      problematic. We hypothesized that the phenotype chemokine RANTES (regulated upon
      activation, normal T cell expressed and secreted) expression of infiltrating
      cells and the pattern of expression of transforming growth factor-beta (TGF-beta)
      may distinguish ACR from QB. In previous studies, the number of RANTES-positive
      cells and the expression of TGF-beta correlated with the severity of rejection.
      METHODS: We used immunohistochemical techniques to stain sections of human EMBs
      with only QB (n = 14) or with only ACR (International Society for Heart and Lung
      Transplantation Grades 1A and 1B, n = 7; Grades 3A and 3B, n = 7) for B (CD20)
      and T-lymphocytes (CD3), macrophages (CD68), RANTES, and TGF-beta expression. We
      graded the percentage of positive cells from 0 to 4 (1 = 1% to 25%; 2 = 26% to
      50%; 3 = 51% to 75%, and 4 = 76% to 100%). RESULTS: When ACR was compared with
      QB, we found no difference in the proportion of myocardial B cells (0.9 +/- 0.3
      vs 1.1 +/- 0.3, p = 0.17); however, we found a lesser proportion of T cells (1.8
      +/- 0.5 vs. 2.8 +/- 0.9, p <0.01) but more macrophages (2.9 +/- 0.5 vs. 1.1 +/-
      0.6, p < 0.0001) in ACR than in QB. We also found more RANTES-positive leukocytes
      in ACR vs. QB (2.8 +/- 1.3 vs. 1.9 +/- 0.9, p = 0.03). In QB, many endocardial
      vessels stained for TGF-beta (2.9 +/- 1.6). Myocardial vessels and injured
      myocytes in both ACR and QB expressed TGF-beta. CONCLUSIONS: In ACR, although T
      lymphocytes are numerous, more than 50% of infiltrating cells are macrophages and
      more than 50% express RANTES. In QB lesions, more than 50% of infiltrating cells
      are T-lymphocytes and less that 50% of leukocytes will express RANTES. B cells
      are present in both ACR and QB, but on average comprise only 25% of the cells
      present. Thus, a relatively simple immunohistochemical analysis of endomyocardial
      biopsies may be useful in distinguishing ACR from QB.

PMID- 11295579
TI  - Distribution and declines in cardiac allograft radionuclide left ventricular
      ejection fractions in relation to late mortality.
AB  - BACKGROUND: Cardiac allograft left ventricular ejection fraction (LVEF) is an
      important measure of left ventricular systolic function. Despite widespread use
      of LVEF after transplantation, its normal range and prognostic value in cardiac
      allografts has not been defined. METHODS: We conducted a retrospective cohort
      study among 292 consecutive adult heart transplant patients. Left ventricular
      ejection fractions were performed at 1, 3, 12, 24, and 48 months after
      transplantation using radionuclide ventriculography. Endomyocardial biopsies
      assessed rejection, right heart catheterization assessed loading conditions, and
      angiography assessed allograft coronary artery disease. We used Cox proportional
      hazards model to examine the predictive value of LVEF on late mortality. RESULTS:
      Of the patients who survived > or =4 years, the mean allograft LVEF decreased 4.7
      units at 3 months, from 63.8 to 59.7; an additional 4.1 units at 12 months, from
      59.7 to 55.6 (p < 0.001); and remained stable afterward. These changes were not
      associated with concurrent changes in loading conditions, episodes of rejection,
      or development of allograft coronary artery disease. Left ventricular ejection
      fraction lower than the 95% normal limit (<40%) at 12 months was inversely
      associated with risk for late cardiac mortality (relative risk = 3.5, 95%
      confidence interval = 1.0-12.2), while controlling for recipient age, sex, donor
      age, and rejection episodes. CONCLUSIONS: The cardiac-allograft LVEF frequently
      decreases in the first year after transplantation. The 95th percentile of
      allograft LVEF value (<40%) at Year 1 predicts late cardiac mortality among
      transplant recipients.

PMID- 11295580
TI  - Hypogammaglobulinemia following cardiac transplantation: a link between rejection
      and infection.
AB  - BACKGROUND: Hypogammaglobulinemia (HGG) has been reported after solid organ
      transplantation and is noted to confer an increased risk of opportunistic
      infections. OBJECTIVES: In this study, we sought to assess the relationship
      between severe HGG to infection and acute cellular rejection following heart
      transplantation. METHODS: Between February 1997 and January 1999, we
      retrospectively analyzed the clinical outcome of 111 consecutive heart transplant
      recipients who had immunoglobulin G (IgG) level monitoring at 3 and 6 months post
      transplant and when clinically indicated. RESULTS: Eighty-one percent of patients
      were males, mean age 54 +/- 13 years, and the mean follow-up period was 13.8 +/-
      5.7 months. Patients had normal IgG levels prior to transplant (mean 1137 +/- 353
      mg/dl). Ten percent (11 of 111) of patients developed severe HGG (IgG < 350
      mg/dl) post-transplant. The average time to the lowest IgG level was 196 +/- 125
      days. Patients with severe HGG were at increased risk of opportunistic infections
      compared to patients with IgG > 350 mg/dl (55% [6 of 11] vs. 5% [5 of 100], odds
      ratio = 22.8, p < 0.001). Compared to patients with no rejection, patients who
      experienced three or more episodes of rejection had lower mean IgG (580 +/- 309
      vs. 751 +/- 325, p = 0.05), and increased incidence of severe HGG (33% [7 of 21]
      vs. 2.8% [1 of 35], p = 0.001). The incidence of rejection episodes per patient
      at 1 year was higher in patients with severe HGG compared to patients with IgG
      >350 (2.82 +/- 1.66 vs. 1.36 +/- 1.45 episodes/patient, p = 0.02). The use of
      parenteral steroid pulse therapy was associated with an increased risk of severe
      HGG (odds ratio = 15.28, p < 0.001). CONCLUSIONS: Severe HGG after cardiac
      transplantation may develop as a consequence of intensification of
      immunosuppressive therapy for rejection and hence, confers an increased risk of
      opportunistic infections. IgG level may be a useful marker for identifying
      patients at high risk.

PMID- 11295581
TI  - Pharmacokinetics of cyclosporine in heart transplant recipients receiving
      metabolic inhibitors.
AB  - BACKGROUND: Inhibitors of cyclosporine metabolism are commonly co-administered
      with cyclosporine in transplant recipients. The aim of this study was to compare
      cyclosporine pharmacokinetics using the conventional formulation (Sandimmune) and
      after switching to the microemulsion (Neoral) formulation, in stable heart
      transplant recipients receiving various cyclosporine metabolic inhibitors.
      METHODS: Steady-state blood concentration-time profiles of Sandimmune were
      studied in 47 transplant recipients receiving either cyclosporine alone (Group A,
      n = 11) or in combination with diltiazem (120 mg/day, Group B, n = 11),
      ketoconazole (200 mg/day, Group C, n = 13), or both ketoconazole and diltiazem
      (200 and 120 mg/day, respectively, Group D, n = 12), and restudied 1 week after
      switching to Neoral. RESULTS: Neoral resulted in more rapid cyclosporine
      absorption as judged by the shorter absorption half-lives in all groups (p <
      0.05). The mean percentage increase in the values of area-under-the-concentration
      time curve was 42% and 37.5% higher for Neoral compared with Sandimmune for
      Groups A and B, respectively, but only 5.4% higher for Group C and 9.5% higher
      for Group D. The mean morning trough concentration of cyclosporine was not
      significantly different after administration of Neoral compared with Sandimmune
      in any of the groups studied (179 vs. 167 microg/liter for Group A; 171 vs. 147
      microg/liter for Group B; 189 vs. 194 microg/liter for Group C; and 181 vs 201
      microg/liter for Group D). Neoral did not alter serum concentrations of sodium,
      potassium, creatinine, and urea in any of the study groups. CONCLUSIONS: The
      faster absorption and improved bioavailability of cyclosporine (around 40%) with
      Neoral compared with Sandimmune was not seen in patients receiving ketoconazole,
      where in fact cyclosporine bioavailability was already maximal. Mean morning
      trough levels of cyclosporine did not reflect the improvement in bioavailability
      seen in patients switching from Sandimmune to Neoral. Cyclosporine dose
      adjustment may be needed when switching from Sandimmune to Neoral for patients
      not receiving sparing agents or who receive diltiazem, but trough levels cannot
      necessarily be relied upon to determine the degree of adjustment needed. For
      patientson ketoconazole, the absorption profile is already optimized and no
      dosage alteration seems necessary.

PMID- 11295582
TI  - Multicenter experience with the thoratec ventricular assist device in children
      and adolescents.
AB  - BACKGROUND: Patient size is 1 determinant in selecting a mechanical circulatory
      support device. The current pulsatile ventricular assist devices (VADs) were
      designed primarily for average-sized adults. The flexibility of the Thoratec VAD,
      however, has encouraged physicians to use it in a significant number of
      intermediate-sized older children and adolescents. METHODS: We conducted a
      retrospective study in 58 children and adolescents <18 years (41 boys, 17 girls)
      who had been supported with the Thoratec VAD in 27 centers worldwide as of
      December 1999. Mean patient age was 13.8 years (range, 7 to 17 years), and mean
      patient weight and body surface area were 51.6 kg (range, 17 to 93 kg) and 1.5
      m(2) (range, 0.7 to 2.1 m(2)), respectively. RESULTS: Thirty-five patients (60%)
      survived to transplantation and 6 (10%) to recovery of the native heart,
      respectively; 38 were discharged from the hospital (66%). In the transplanted
      group, post-transplantation survival was 97%. Patient age and size were not
      associated with significantly increased risk for death or adverse events. Fifteen
      patients (27%) had 18 neurologic events during support, and 6 of these were
      fatal. Left atrial cannulation proved a risk factor for neurologic complications.
      CONCLUSIONS: The Thoratec VAD has successfully been used in a large number of
      children and adolescents with similar morbidity and mortality results as with
      adults. The risk of neurologic complications may be increased, particularly in
      patients cannulated in the left atria.

PMID- 11295583
TI  - Cardiac transplant outcome of patients supported on left ventricular assist
      device vs. intravenous inotropic therapy.
AB  - BACKGROUND: Although the left ventricular assist device (LVAD) has been
      increasingly used as a bridge to transplant, its effect on post-transplant
      outcome is uncertain. We, therefore, designed this study using the Cardiac
      Transplant Research Database to compare patients supported on an LVAD before
      transplant with those treated with intravenous inotropic medical therapy. METHODS
      AND RESULTS: Of the 5,880 patients transplanted between 1990 and 1997, a total of
      502 received support from LVADs and 2,514 received intravenous inotropic medical
      therapy at the time of transplant. Kaplan-Meier analysis showed no significant
      difference in post-transplant survival between the LVAD and medical-therapy
      groups (p = 0.09). Results of a multivariate Cox regression analysis were
      consistent with that of the Kaplan-Meier analysis and did not identify LVAD as a
      significant risk factor for mortality. The percentage of patients who received
      LVADs as a function of total transplants increased from 2% in 1990 to 16% in
      1997. Furthermore, although the number of extracorporeal LVADs remained
      relatively constant, the number of intracorporeal LVADs increased over time.
      Multivariate parametric analysis found that the risk factors for post-transplant
      death in the LVAD group were extracorporeal LVAD use (p = 0.0004), elevated serum
      creatinine (p = 0.05), older donor age (p = 0.03), increased donor ischemic time
      (p < 0.0001), and earlier year of transplant (p = 0.03). CONCLUSIONS: Given a
      limited donor supply, the intracorporeal LVAD helps the sickest patients survive
      to transplant and provides post-transplant outcome similar to that of patients
      supported on inotropic medical therapy. Therefore, patients supported on LVADs
      before transplant may receive the greatest marginal benefit when compared with
      other transplant candidates.

PMID- 11295584
TI  - Regression of fibrosis and hypertrophy in failing myocardium following mechanical
      circulatory support.
AB  - BACKGROUND: The cellular and structural changes that occur during long-term
      ventricular unloading leading to cardiac recovery are poorly understood. However,
      we have previously demonstrated that left ventricular assist device (LVAD)
      support leads to a significant decrease in intracardiac tumor necrosis factor
      alpha (TNF-alpha), a protein capable of producing hypertrophy and fibrosis.
      METHODS: To further define the beneficial effects of long-term ventricular
      unloading on cardiac function, we determined the effect of mechanical circulatory
      support on fibrosis and hypertrophy in paired myocardial samples of 18 patients
      with end-stage cardiomyopathy obtained at the time of LVAD implantation and
      removal. RESULTS: We determined total collagen as well as collagen I and III by a
      semiquantitative analysis of positive immune-stained areas in pre- and post-LVAD
      myocardial samples. We found that total collagen content was reduced by 72% (p <
      0.001), whereas collagen I content decreased by 66% (p < 0.001) and collagen III
      content was reduced by 62% (p < 0.001). Next, we determined myocyte size by
      direct analysis of cellular dimensions utilizing a computerized edge detection
      system in pre- and post-LVAD myocardial samples. We found that myocyte size
      decreased in all patients studied for an average reduction of 26% (33.1 +/- 1.32
      to 24.4 +/- 1.64 microm, p < 0.001). CONCLUSION: These data demonstrate that long
      term mechanical circulatory support significantly reduces collagen content and
      decreases myocyte size. We suggest that the reduction of fibrosis and hypertrophy
      observed may in part contribute to the recovery of cardiac function associated
      with long-term mechanical circulatory support.

PMID- 11295585
TI  - Angiogenesis stimulation in explanted hearts from patients pre-treated with
      intravenous prostaglandin E(1).
AB  - BACKGROUND: Prostaglandin E(1) (PGE(1)) is a potent vasodilator and induces
      angiogenesis in animal tissues. Previous clinical studies demonstrated that
      PGE(1) improves hemodynamic parameters in patients with heart failure listed for
      heart transplantation (HTX). Therefore, we designed a retrospective
      immunohistochemistry study to investigate various markers of angiogenesis using
      hearts explanted from PGE(1)-treated patients with idiopathic dilated
      cardiomyopathy (IDCM). METHODS AND RESULTS: We investigated neovascularization in
      18 hearts explanted from patients with IDCM: 9 patients received treatment with
      chronic infusions of PGE(1) for end-stage heart failure before HTX, whereas the
      remaining patients with IDCM did not receive PGE(1) and served as controls. We
      used immunoreactivity against CD34, von Willebrand factor (vWf), vascular
      endothelial growth factor (VEGF), and MIB-1 (Ki-67) to quantify angiogenesis, and
      used sirius red staining to determine the degree of fibrosis. Compared with the
      control group, PGE(1)-treated patients had significantly more CD34-, vWf- and MIB
      1-positive cells in the sub-endocardium, myocardium and sub-epicardium (p <
      0.01). The degree of fibrosis in the hearts of PGE(1)-treated patients was
      significantly lower than in control patients (p < 0.05), but we did not see any
      difference in the percentage of muscle mass. Finally, throughout the ventricles,
      we found significantly more VEGF-positive capillaries in the PGE(1) group (p <
      0.0001). CONCLUSIONS: The data suggest that PGE(1) could be a potent inducer of
      angiogenesis and the angiogenic factor VEGF, and could cause reduced fibrosis in
      the failing human heart.

PMID- 11295586
TI  - A model for analyzing the cost of the main clinical events after lung
      transplantation.
AB  - BACKGROUND: The aim of this project was to model clinically important events
      experienced by lung transplant patients (from the day after transplant to 5 years
      or death) and costs associated with these events, and to assess the economic
      impact of different immunosuppression therapies. METHODS: The population
      comprised 356 lung transplant patients (223 heart-lung, 102 single lung and 31
      double lung) transplanted between April 1984 and December 1997. All patients
      received a cyclosporine-based triple-immunosuppression protocol. We designed a
      Markov model that included 3 time periods (0 to 6, 7 to 12, and 13 to 60 months),
      5 clinical states (well, acute rejection, cytomegalovirus infection, non
      cytomegalovirus infection and bronchiolitis obliterans syndrome), and death. For
      the well state, cost elements were immunosuppression, prophylaxis, and routine
      clinic visits. For all other states, cost elements were diagnosis, treatment, and
      bed days/visits. We excluded costs of the procedure. RESULTS: The monthly costs
      associated with the well state decreased over time, from pound sterlings 1,778
      ($2,658) in the first 6 months to pound sterlings 503 ($752) in months 7 to 12
      and pound sterlings 350 ($523) after the first 12 months. The cost per event of
      the acute states remained reasonably constant over the 3 periods: pound sterlings
      1,850 ($2,766) for rejection, pound sterlings 3,380 ($5,053) for cytomegalovirus,
      and pound sterlings 2,790 ($4,171) for other infections. The average cost per
      patient, discounted at 6%, over 5 years was pound sterlings 35,429 ($52,966) (95%
      range, pound1,435 [$2,145] to pound67,079 [$100,283]). This estimate is most
      sensitive to changes in immunosuppression. Substituting tacrolimus for
      cyclosporine increased 5-year costs by 5%; substituting mycophenolate mofetil for
      azathioprine increased 5-year costs by 26%. CONCLUSIONS: This model is valuable
      in estimating the effect of new immunosuppression agents on the costs of follow
      up care.

PMID- 11295587
TI  - Bacterial endocarditis: a rare complication following orthotopic cardiac
      transplantation.
AB  - We describe a 46-year-old man who developed infective endocarditis, meningitis,
      sternal abscess, and infective cerebral emboli after cardiac transplantation.
      Staphylococcus aureus was the infective organism. We successfully managed the
      patient with flucloxacillin and fusidic acid to treat infection, and with
      prostacyclin for systemic embolization.

PMID- 11295588
TI  - Mycobacterium marinum infection in a lung transplant recipient.
AB  - We report a case of Mycobacterium marinum infection in a lung transplant
      recipient who presented with nodules on the hand and forearm following exposure
      to fish-tank water of a superficial hand burn. Skin biopsy revealed granulomatous
      inflammation and fibrosis. Tissue culture grew Mycobacterium marinum. The patient
      underwent surgical excision of the lesions and treatment with ethambutol and
      azithromycin for 12 months and experienced complete resolution of the infection.
      Transplant recipients who receive immunosuppressive therapy are at increased risk
      for opportunistic infections. For a patient with nodular lesions on the
      extremities, exposure to fish, fish-tank water, or swimming should suggest
      infection with Mycobacterium marinum.

PMID- 11295589
TI  - Introduction.

PMID- 11295591
TI  - State of research for prostate cancer: Excerpt from the report of the Prostate
      Cancer Progress Review Group.
AB  - The following is an excerpt from a report entitled: "Defeating Prostate Cancer:
      Crucial Directions for Research." The report, which was submitted to the Advisory
      Committee to the Director of the National Cancer Institute, summarizes the
      findings and recommendations of the Progress Review Group.

PMID- 11295590
TI  - Executive Summary of the National Cancer Institute Workshop: Highlights and
      recommendations.
AB  - Prostate cancer chemoprevention represents a relatively new and promising
      strategy for reducing the immense public health burden of this devastating cancer
      of men in the United States and Western societies. Chemoprevention is defined as
      the administration of agents (drugs, biologics, and natural products) that
      modulate (inhibit) one or more steps in the multistage carcinogenesis process
      culminating in invasive adenocarcinoma of the prostate. In 2000, there were an
      estimated 170,000 new cases of prostate cancer and 31,000 deaths in the United
      States. During the past decade, the National Cancer Institute (NCI) organized the
      chemoprevention research program and began testing the first generation of
      promising agents (eg, 4-(hydroxy)-fenretinide [4-HPR], difluoromethylornithine
      [DFMO], antiandrogens) in high-risk cohorts and launched the first-large scale US
      phase 3 primary prevention trial, known as Prostate Cancer Prevention Trial (PCPT
      1), in 18,000 average-risk men (age more than 55 years and prostate-specific
      antigen [PSA] less than 3 ng/mL) treated for 7 years with finasteride or placebo.
      In the summer of 1998, the NCI Prostate Cancer Progress Review Group (PRG) Report
      to the director of NCI was published in response to the leadership of the
      prostate cancer advocacy community in conjunction with Congress. To further
      elucidate and address critical issues identified in this report and to develop a
      research agenda for the newly created Prostate and Urologic Cancer Research Group
      in the Division of Cancer Prevention at NCI, the NCI organized the workshop "New
      Clinical Trial Strategies for Prostate Cancer Chemoprevention." The major
      objectives were to promote understanding and cooperation among the NCI, US Food
      and Drug Administration (FDA), academia, pharmaceutical industry, and the public
      regarding new opportunities for clinical prevention trials for prostate cancer.
      The workshop was divided into three concurrent breakout panels and a fourth joint
      integrative panel. The workshop addressed multiple key areas identified in the
      PRG report in the following panels: (1) Molecular Targets and Promising Agents in
      Clinical Development; (2) Intermediate Endpoint Biomarkers for Prevention Trials;
      (3) High-Risk Study Populations for Prevention Trials, and (4) Preventive
      Clinical Trial Designs and Regulatory Issues. Expert panelists were drawn from
      leading academic, pharmaceutical, and government scientists in basic research and
      clinical investigation. Key pharmaceutical, biotechnology, academic, and National
      Institutes of Health scientists presented overviews of their new agents and
      products in clinical development (representing the next generation of promising
      agents). Senior FDA physicians from the Center for Drugs and Center for Biologics
      presented on current standards for new drug and biologic approval for
      chemoprevention efficacy. Some of the key topics included recent advances in the
      state of knowledge of promising agents in the clinic based on molecular targets
      as well as bottlenecks in drug development for pharmaceutical sponsors; strategic
      modulable biomarkers that can serve as primary endpoints in phase 1/2 trials to
      assess preventive efficacy; high-risk cohorts with precancer (high-grade
      prostatic intraepithelial neoplasia) and representative clinical trial designs
      that are ready for immediate translation into efficient prevention trials, such
      as Bayesian sequential monitoring for early assessment of biologic activity and
      factorial designs for assessment of multiagent combinations. Finally, each expert
      panel generated recommendations for areas of future research emphasizing
      opportunities and infrastructure needs.

PMID- 11295592
TI  - Similarities of prostate and breast cancer: Evolution, diet, and estrogens.
AB  - Environment determines the risk of both prostate and breast cancer, and this risk
      can vary >10-fold. In contrast, no risk exists for human seminal vesicle cancer
      demonstrating tissue specificity. There is also species specificity, because
      there is no risk for prostate cancer in any other aging mammal except the dog. A
      study of evolution indicates that the prostate and breast appeared at the same
      time 65 million years ago with the development of mammals. All male mammals have
      a prostate; however, the seminal vesicles are variable and are determined by the
      diet so that species primarily eating meat do not have seminal vesicles. The
      exception is the human, who has seminal vesicles and consumes meat, although this
      is a recent dietary change. Human lineage departed from other higher primates 8
      million years ago. The closest existing primate to humans is the bonobo (pigmy
      chimpanzee), which does not eat meat but exists primarily on a high fruit and
      fresh vegetable diet. Homo sapiens evolved only about 150,000 years ago, and only
      in the last 10% of that time (10 to 15 thousand years ago) did humans and dogs
      dramatically alter their diets. This is the time when humans domesticated the
      dog, bred animals, grew crops, and cooked, processed, and stored meats and
      vegetables. All current epidemiologic evidence and suggestions for preventing
      prostate and breast cancer in humans indicates that we should return to the
      original diets under which our ancestors evolved. The recent development of the
      Western-type diet is associated with breast and prostate cancer throughout the
      world. It is believed that the exposure to and metabolism of estrogens, and the
      dietary intake of phytoestrogens, combined with fat intake, obesity, and burned
      food processing may all be related to hormonal carcinogenesis and oxidative DNA
      damage. An explanatory model is proposed.

PMID- 11295593
TI  - The molecular pathogenesis of prostate cancer: Implications for prostate cancer
      prevention.
AB  - Prostate cancer has become 1 of the most commonly diagnosed cancers in the United
      States and 1 of the leading causes of cancer death in North America and Western
      Europe. Survey studies of prostate tissues obtained at autopsy indicate that the
      development of life-threatening prostate cancer in the US likely occurs over
      decades. Insights from epidemiologic studies implicate environmental factors,
      principally dietary components, as major risk factors for prostate cancer
      development. An accumulating body of basic research data suggests that normal and
      neoplastic prostate cells may be subjected to a relentless barrage of genome
      damaging stresses, and that dietary components and male sex steroids might
      modulate the level of genome threatening insults. Finally, over the past 5 years,
      analyses of somatic genome alterations in prostatic carcinoma cells have revealed
      that somatic inactivation of GSTP1, encoding the carcinogen-detoxification enzyme
      glutathione S-transferase pi, may serve as an initiating genome lesion for
      prostatic carcinogenesis. These diverse observations can be integrated into a
      transcendent mechanistic hypothesis for the pathogenesis of prostate cancer:
      normal prostate cells acquiring somatic GSTP1 defects may suffer chronic genome
      damage, influenced by dietary practices, that promote neoplastic transformation,
      while prostatic carcinoma cells, which characteristically contain defective GSTP1
      alleles, remain susceptible to further genome-damaging stresses that promote
      malignant cancer progression. This hypothesized critical role for GSTP1
      inactivation in the earliest steps of prostatic carcinogenesis provides several
      attractive opportunities for prostate cancer prevention strategies, including (1)
      restoration of GSTP1 function, (2) compensation for inadequate GSTP1 activity
      (via use of therapeutic inducers of other glutathione S-transferases (GST), and
      (3) abrogation or attenuation of genome-damaging stresses.

PMID- 11295594
TI  - Agents, biomarkers, and cohorts for chemopreventive agent development in prostate
      cancer.
AB  - Chemoprevention is the use of agents to slow progression of, reverse, or inhibit
      carcinogenesis thereby lowering the risk of developing invasive or clinically
      significant disease. With its long latency, high incidence and significant
      morbidity and mortality, prostate cancer is a relevant target for
      chemoprevention. Developing rational chemopreventive strategies for prostate
      cancer requires well-characterized agents, suitable cohorts, and reliable
      intermediate biomarkers of cancer. Chemopreventive agent requirements are
      experimental or epidemiologic data showing efficacy, safety on chronic
      administration, and a mechanistic rationale for activity. Current promising
      agents include antiandrogens and antiestrogens; steroid aromatase inhibitors;
      retinoids and their modulators; 5alpha-reductase inhibitors; vitamins D, E, and
      analogs; selenium compounds; carotenoids; soy isoflavones;
      dehydroepiandrostenedione and analogs; 2-difluoromethylornithine; lipoxygenase
      inhibitors; apoptosis inducers; and nonsteroidal anti-inflammatory drugs.
      Identifying biomarkers and validating them as surrogate endpoints for cancer
      incidence are critical for prostate chemoprevention trials. Potentially useful
      biomarkers for prostate chemoprevention are associated with histologic,
      proliferative, differentiation-related, biochemical, and genetic/regulatory
      features of prostatic disease. In that the prostate is not easily visualized,
      critical issues also include adequacy and consistency of tissue sampling. Various
      drugs for the chemoprevention of prostate cancer are now under evaluation in
      phase 1, 2, and 3 clinical trials. Cohort selection should be based on various
      patient characteristics (stage of the disease, previous cancers or premalignant
      lesions, or high risk factors) and should be conducted within the context of
      standard treatment.

PMID- 11295595
TI  - Sustaining the effort for cancer prevention.
AB  - The Cancer Research Foundation of America has played a key role in "fueling the
      engine" of cancer prevention progress through a national research grant and
      education program. It is one of the nation's leading cancer prevention
      organizations, and has helped move prevention science from the fringes to the
      mainstream. Since its inception in 1985, it has provided more than $42.1 million
      in funding for cancer prevention research and education. It has supported
      pioneering research and translated it into practical information to educate men,
      women, and children about how to reduce their cancer risk. As more and more
      research results in practical interventions to prevent cancer, the Foundation
      will continue to act in an anticipatory way to help smooth the way for rapid
      translation of information from scientific study to consumer information through
      education and awareness initiatives. As we celebrate our 15th anniversary, the
      Cancer Research Foundation of America has recommitted itself to its role as a
      catalyst for change. It hopes to help the nation move toward a future in which
      harsh and often toxic treatment for cancer is replaced with a sane policy of cost
      effective early intervention-healthy lifestyle education, detection of
      premalignant conditions, and therapies that spare healthy tissue. The Foundation
      believes there is a groundswell of support for making cancer prevention and early
      detection a national priority.

PMID- 11295596
TI  - Prostate cancer prevention agent development: Criteria and pipeline for candidate
      chemoprevention agents.
AB  - Epidemiologic data suggest that prostate cancer morbidity and mortality ought to
      be preventable. New insights into the molecular pathogenesis of prostate cancer
      offer new opportunities for the discovery of prostate cancer chemoprevention
      drugs and new challenges for their development. Established pathways that lead to
      US Food and Drug Administration (FDA) approval of drugs for advanced prostate
      cancer may not be appropriate for the development of drugs for prostate cancer
      chemoprevention. For example, large randomized clinical trials designed to test
      the efficacy of new chemoprevention drugs on prostate cancer survival in the
      general population are likely to be conducted at great expense and take many
      years, threatening to increase commercial development risks while decreasing
      exclusive marketing revenues. As a consequence, to accelerate progress in
      research, new validated surrogate and strategic clinical trial endpoints, and new
      clinical trial designs featuring more precisely defined high-risk clinical trial
      cohorts, are needed. In this review, 10 criteria for prostate cancer
      chemoprevention agent development are offered and the pipeline of new prostate
      cancer chemoprevention drug candidates is considered.

PMID- 11295597
TI  - Androgen antagonists: Potential role in prostate cancer prevention.
AB  - This article summarizes discussions of the importance of androgens and androgen
      antagonists in the genesis of prostate cancer. These discussions occurred at a
      recent symposium on prostate cancer chemoprevention sponsored by the National
      Cancer Institute. Considerable information exists indicating the importance of
      androgens in the development of prostate cancer. Trials in breast cancer indicate
      that estrogen antagonists prevent breast cancer-suggesting, by analogy, that the
      blockade of androgen action might prevent the emergence of prostate cancer. The
      5alpha-reductase inhibitors block the intracellular metabolism of testosterone
      and inhibit the growth of the prostate. Limited data suggest that 5alpha
      reductase inhibitors reduces prostate-specific antigen in men with localized and
      advanced, primary or recurrent prostate cancer. An ongoing national trial of
      18,000 men over 50 years of age has completed accrual and will evaluate whether a
      standard dose of finasteride will prevent the development of prostate cancer. The
      toxicity profile of finasteride (Proscar, Merck & Co., West Point, PA), the only
      approved 5alpha-reductase inhibitor, is favorable leading to its evaluation as a
      potential chemopreventive agent for prostate cancer. Anti-androgens such as
      bicalutamide (Casodex, AstraZeneca, Wilmington, DE) are active in the treatment
      of prostate cancer and comparable, in some trials, to testicular androgen
      suppression. These data suggest that antiandrogens may be active in the
      prevention of prostate cancer; however, the toxicity of antiandrogens
      (gynecomastia, gastrointestinal toxicity) poses concerns for application in
      prevention studies. Opportunities for study of factors predictive or associated
      with the development of prostate cancer and new agents that may interrupt this
      process offer numerous leads that may reduce the incidence of prostate cancer.

PMID- 11295598
TI  - Selective estrogen receptor modulators for the chemoprevention of prostate
      cancer.
AB  - The ability to interfere with prostate carcinogenesis, and as a consequence,
      prevent prostate cancer with drugs is the basis for chemoprevention. The prostate
      contains estrogen receptors in both the stroma and epithelium. Both animal models
      and human epidemiologic studies have implicated estrogens as an initiator of
      prostate cancer. In the aging male, prostate cancer occurs in an environment of
      rising estrogen and decreasing androgen levels. Selective estrogen receptor
      modulators (SERMs) have shown the ability to prevent (GTx-006 [acapodene]) and
      treat (GTx-006 and arzoxifene) prostate cancer, suggesting that they may be used
      in prostate cancer chemoprevention. A phase 2 clinical trial using GTx-006 for
      prostate cancer chemoprevention is currently being conducted.

PMID- 11295599
TI  - Proapoptotic anti-inflammatory drugs.
AB  - The very fact that apoptosis and nonsteroidal anti-inflammatory drugs (NSAIDs)
      can be linked in the same title should tell you that something unusual is
      happening. The image of NSAIDs among physicians is certainly discordant with that
      associated with cancer treatment, which usually involves administration of drugs
      with serious or even life-threatening toxicity. In contrast, the drugs discussed
      in this review, including selective cyclooxygenase-2 inhibitors, lipoxygenase
      inhibitors, and novel NSAID derivatives (eg, sulindac sulfone and R
      flurbiprofen), offer the promise of oral, nontoxic agents able to control the
      progression of established prostate cancer and possibly to prevent the
      development of prostate cancer de novo. NSAIDs were initially developed to
      suppress inflammation and pain by inhibiting the production of prostaglandin E2
      and its metabolites. At first glance, the fact that NSAIDs are active against
      prostate cancer in laboratory and clinical studies might suggest that
      prostaglandins play a pivotal role in prostate cancer biology. However, the story
      is much more complex than that. Although cyclooxygenase-mediated production of
      prostaglandins appears to play an important role in the biology of prostate
      cancer, the NSAIDs and derivatives with promising activity against prostate
      cancer manifest several mechanisms of action that can include direct inhibition
      of eicosanoid formation, indirect inhibition of eicosanoid formation by
      inhibiting expression of enzymes involved in eicosanoid synthesis, or by
      interfering with the function of cyclic guanosine monophosphate.

PMID- 11295600
TI  - Tyrosine kinase inhibitors and signal transduction modulators: Rationale and
      current status as chemopreventive agents for prostate cancer.
AB  - Cell growth and differentiation are processes intimately associated with
      carcinogenesis and regulated by tyrosine kinases and other signaling proteins.
      Identification of drugs that target signaling molecules is hampered by both the
      large number of targets and the complex nature of signaling cascades. Optimal
      development of chemopreventive agents must take into account affinity for the
      target, pharmacology, and safety profile of the agent. Validated biomarkers will
      allow the optimal implementation of chemopreventive trials. Directed
      epidemiologic studies can lead to the identification of lead compounds for
      chemoprevention, such as genistein. Therefore, agents targeted to pathways and
      molecules of known biological importance in the prostate hold the promise of
      clinical efficacy against prostate cancer in a chemopreventive setting.

PMID- 11295601
TI  - Prostate cancer prevention strategies using antiproliferative or differentiating
      agents.
AB  - Differentiation or antiproliferative therapies have been most effective in the
      treatment of promyelocytic leukemia and are being investigated for the treatment
      of solid tumors including prostate cancer (PCa). Research suggests that these
      agents may induce terminal differentiation (arrest in G(0)), induce
      differentiation to a mature cell with cellular functions and a growth pattern
      similar to nonmalignant cells, or trigger apoptosis. This review focuses on
      classes of agents under laboratory and clinical evaluation as antiproliferative
      or differentiating agents: polyamine inhibitors, vitamin D and its analogs,
      metabolites of vitamin A, the short-chain fatty acid, phenylbutyrate, and
      nonsteroidal anti-inflammatory agents. Because differentiation therapies offer a
      reduced toxicity profile and have potential for preventing or slowing cancer
      progression, they may offer an alternative to chemotherapy for men with advanced
      PCa, or may be useful as low-toxicity agents given chronically for
      chemoprevention in men at high risk for PCa. Clinical trials are needed to define
      the role of these agents in primary and secondary prevention.

PMID- 11295602
TI  - Other novel agents: Rationale and current status as chemopreventive agents.
AB  - Several novel targets are currently being evaluated both preclinically and
      clinically for the prevention of prostate cancer. Four divergent and novel
      approaches were discussed at the National Cancer Institute-sponsored workshop
      entitled, "New Clinical Strategies in Prostate Cancer Prevention." These
      interventions are further categorized into soy protein-based serine-protease
      inhibitors that reduce superoxide-induced DNA damage, and molecularly targeted
      approaches that are directed toward endothelin-1 expression/overexpression,
      peroxisome proliferator-activated receptor ligands, and insulinlike growth
      factors. Understanding each of these approaches has offered insights into the
      process of malignant transformation of prostatic epithelium, and further
      illustrates the difficulties of developing new agents in the treatment and
      prevention of prostate cancer. Close scrutiny of the clinical data emerging with
      these approaches, including validation of biologic endpoints, is required before
      large-scale prevention studies with these novel agents and targets can be
      considered.

PMID- 11295603
TI  - Antioxidant dietary supplements: Rationale and current status as chemopreventive
      agents for prostate cancer.
AB  - Epidemiologic data suggest that the environment is responsible for most prostate
      cancers (PCA). One major mechanism by which the environment can influence
      carcinogenesis is oxidative damage. This refers to the generation of reactive
      oxygen species (ROS) that then damage important biomolecules, including DNA,
      protein, and lipids. Experimental observations suggest that oxidative damage is
      associated with PCA. These include: a) the association of PCA and dietary fat
      consumption (a major substrate for oxidative stress), b) oxidative biomarker data
      (suggesting increased oxidative stress among patients with PCA), c) ubiquitous
      defects in the glutathione-s-transferase pi pathway (a major endogenous
      antioxidant mechanism), and d) evidence that androgens (an important promoter of
      PCA growth) work in part via generation of ROS. Perhaps the best indirect
      evidence for oxidative stress comes from randomized double-blind prevention
      trials of antioxidants. Vitamin E and selenium have both been shown to reduce
      prostate cancer incidence. Although PCA prevention was not the primary endpoint
      of these studies, the statistical likelihood that both would prove beneficial by
      chance alone is 1 in 400. These data suggest that antioxidants may be beneficial
      in preventing PCA. Further research including randomized trials is warranted.

PMID- 11295604
TI  - New biologicals for prostate cancer prevention: Genes, vaccines, and immune-based
      interventions.
AB  - For at least 100 years, immunologists have proposed activating the immune system
      to specifically target and eradicate autologous tumor cells. The idea that tumor
      cells can be recognized as foreign to the host's immune system is an essential
      concept of tumor immunology that was first postulated by Paul Ehrlich at the turn
      of the century. Anecdotal reports of spontaneous tumor regression have been
      presumed to be immunologically mediated. With the advent of molecular gene
      transfer techniques and increased knowledge of the regulation of the immune
      response, effective methods for harnessing the immune system as a therapeutic
      agent are finally being realized. Current results of clinical immune/gene therapy
      protocols will be reviewed with consideration towards the concept of cancer
      prevention.

PMID- 11295605
TI  - New molecular approaches for identifying novel targets, mechanisms, and
      biomarkers for prostate cancer chemopreventive agents.
AB  - Recently developed complementary DNA (cDNA) microarray technology allows
      simultaneous assessment of expression on many hundreds or thousands of genes
      simultaneously. This technology holds great promise for providing new insights
      into prostate carcinogenesis that will reveal new targets for preventive
      intervention strategies. In addition, this technology will deepen understanding
      of the means by which putative preventive compounds exert their effects,
      generating molecular genetic biomarkers of treatment efficacy. Several putative
      preventive agents are currently under investigation, and development of novel
      preventive strategies poses significant challenges. High throughput approaches,
      such as cDNA microarrays, will speed discovery and progress in prostate cancer
      chemoprevention.

PMID- 11295606
TI  - New concepts in the pathology of prostatic epithelial carcinogenesis.
AB  - The development of drugs to prevent prostate cancer is underway, yet monitoring
      the potential efficacy of these agents during clinical trials relies on measuring
      intermediate endpoints. In this review, various candidate markers are presented
      that are under different stages of evaluation as intermediate endpoint
      biomarkers. In addition, the near future will bring an unprecedented wave of new
      potential biomarkers. For instance, through genomics-based methods many new genes
      are being discovered whose altered expression may be involved in different phases
      of prostate cancer development and progression. In the development of rational
      approaches for selecting which of these untested biomarkers may be useful to
      measure systematically, there must be an improved understanding of the mechanisms
      of prostatic carcinogenesis. We submit that this improved understanding will come
      through new knowledge of the biology of normal prostate epithelial cells, the
      determination of the precise target cells of transformation, and how their growth
      regulation is genetically and epigenetically perturbed during the phases of
      initiation and progression. In this review, therefore, we also present our recent
      immune-mediated oxidant injury and regeneration hypothesis of why and how the
      prostate is targeted for carcinogenesis.

PMID- 11295607
TI  - Histological markers of risk and the role of high-grade prostatic intraepithelial
      neoplasia.
AB  - The marked discrepancy between the prevalence of preclinical prostate cancer and
      the incidence of clinically manifest disease indicates a long latency phase and
      significant heterogeneity in the progression potential of early neoplastic
      lesions. There are a variety of histologic changes within prostatic epithelium
      that have been termed atypical or dysplastic. The 2 most widely studied of these
      lesions are prostatic intraepithelial neoplasia (PIN) and atypical adenomatous
      hyperplasia (AAH). Although associations between AAH and adenocarcinoma are
      spurious, those linking high-grade PIN (HGPIN) to cancer are far more
      established. There is a significantly increased risk for patients with isolated
      HGPIN to have prostate cancer confirmed on subsequent biopsy, suggesting that
      HGPIN is a marker for prostate carcinoma in addition to its potential role as a
      premalignant lesion. Autopsy studies reveal that HGPIN is found in association
      with cancer in 63% to 94% of malignant and 25% to 43% of benign prostates. Data
      on age and race reveal that African American men develop more extensive HGPIN at
      a younger age than white men. A wide spectrum of molecular/genetic abnormalities
      appears to be common to both HGPIN and prostate cancer. Data loss of 8p, 10q,
      16q, 18q, and gain of 7q31, 8q, multiple copies of the c-myc genes, along with
      changes in chromatin texture, telomerase activity, cell cycle status, and
      proliferative indices collectively suggest that HGPIN is intermediate between
      benign epithelium and prostatic carcinoma with respect to these markers. These
      data indicate that HGPIN is important in neoplastic progression, and may present
      an appropriate target/marker for chemoprevention.

PMID- 11295608
TI  - Imaging and prostate cancer chemoprevention: Current diagnosis and future
      directions.
AB  - Identifying appropriate patients as targets for prostate cancer chemoprevention
      is a daunting task due to the multiple known and unknown factors contributing to
      patients' risk profiles. Confirmation of the extent and location of early
      prostate cancers, as well as prostatic intraepithelial neoplasia (PIN), also
      requires improved image guidance of biopsy to contain costs. Prostate-specific
      antigen (PSA) in conjunction with transrectal ultrasound (TRUS) and digital
      rectal examination (DRE) have been the front-line tests for early prostate
      cancer. Although advances in MRI continue to improve its accuracy, limited
      availability and higher costs preclude its widespread use for chemoprevention
      trials. Improved biopsy risk assessment has been achieved by categorizing TRUS
      grayscale and vascular findings for each biopsy region. In addition, concomitant
      suspicious TRUS findings also improved cancer yield per biopsy, as well as the
      amount and grade of tumor per core. However, TRUS remains operator dependent
      despite advancements in grayscale and vascular imaging. Additional risk
      parameters are needed to better localize small disease foci and improve the
      overall diagnostic performance while containing costs. Future work may improve
      the specificity of tissue characterization to produce reliable noninvasive
      biomarkers for monitoring chemoprevention responses of early prostate cancer or
      PIN.

PMID- 11295609
TI  - Magnetic resonance imaging and spectroscopic imaging: Improved patient selection
      and potential for metabolic intermediate endpoints in prostate cancer
      chemoprevention trials.
AB  - In the design of prostate cancer chemoprevention trials there is a clear need for
      improved patient selection and risk stratification, as well as the use of
      biomarkers that could provide earlier assessment of therapeutic efficacy. Studies
      in preprostatectomy patients have indicated that the metabolic information
      provided by 3-dimensional magnetic resonance spectroscopic imaging (3D-MRSI)
      combined with the morphologic information provided by magnetic resonance imaging
      (MRI) can improve the assessment of cancer location and extent within the
      prostate, extracapsular spread, and cancer aggressiveness. Additionally, pre- and
      posttherapy studies have demonstrated the potential of MRI/3D-MRSI to provide a
      direct measure of the presence and spatial extent of prostate cancer after
      therapy, a measure of the time course of response, and information concerning the
      mechanism of therapeutic response. These studies suggest that the addition of
      MRI/3D-MRSI data to prostate-specific antigen and biopsy data may improve patient
      selection and risk stratification for chemoprevention trials, improve tissue
      sampling for ex vivo molecular marker analysis, and provide shorter-term
      endpoints in chemoprevention trials. However, future studies are necessary to
      establish the ability of MRI/3D-MRSI to accurately assess patients with
      premalignant or very early malignant changes, to validate metabolic markers as
      intermediate endpoints in chemoprevention trials, and to correlate metabolic
      endpoints with other promising intermediate biomarkers.

PMID- 11295610
TI  - Computer-assisted image analysis-derived intermediate endpoints.
AB  - The development of prostatic lesions undergoes a slow progression. To establish
      efficacy of chemopreventive intervention it is therefore necessary to define
      surrogate endpoint biomarkers. Such biomarkers should be sensitive in their
      ability to indicate response. They should be objective, ie, the result of
      measurement, and numerically defined so that a statistical validation of response
      is possible. They should be able to indicate not only a halt of progression of a
      lesion, but also a reversal of progression. The spatial and statistical
      distribution of nuclear chromatin in the secretory and luminal cells in prostatic
      intraepithelial neoplastic lesions has been shown to be well defined. It can be
      represented by a set of features. These have been used to define a progression
      curve along which progression or regression of a lesion can be assessed. One
      could define a fixed endpoint, or one might choose to accept a statistically
      significant regression along the progression curve as criterion for
      chemopreventive efficacy. Expected difficulties could arise from lesion
      heterogeneity, as it would affect the sampling, and from multifocal lesions of
      differing progressions. Lesion heterogeneity thus limits the precision with which
      regression could be detected. These problems might be partially overcome by
      observations taken in histologically normal appearing regions of the prostate.
      The nuclear chromatin pattern of secretory cell nuclei measured in such tissue
      regions from prostates harboring intraepithelial or malignant lesions has been
      shown to exhibit distinctive changes from the chromatin pattern seen in secretory
      cell nuclei from prostates free from any such lesions. These changes appear to be
      expressed in the tissue up to a substantial distance from a lesion. The
      expression of changes in the nuclear chromatin suggests the existence of an
      intraepithelial preneoplastic lesion that can be detected by biomarkers, but
      which is not apparent from visual microscopic inspection. Since chemoprevention
      might be expected to be most effective at the earliest stages of lesion
      development, the assessment of such early alterations is seen as highly relevant
      to efforts to validate the efficacy of chemopreventive intervention.

PMID- 11295611
TI  - Prostate-specific antigen and new serum biomarkers for evaluation of
      chemopreventive agents.
AB  - A great deal of effort regarding the basic understanding and clinical relevance
      of the prevention of prostate cancer has emerged over the past decade.
      Chemoprevention or the administration of a drug or other agent in an attempt to
      prevent, inhibit, or delay the progression of localized prostate cancer has
      gained the most recent attention. Efforts have focused primarily in the
      identification of bioactive chemopreventive agents, risk factors identifying
      individuals with the highest likelihood of developing prostate cancer, pathologic
      identification of premalignant lesions, and epidemiologic studies to better
      understand the natural history of early prostate cancer. However, less work has
      been focused on identifying and characterizing our presently available biomarkers
      in an attempt to validate their use as surrogate endpoints or documenting their
      clinical utility in chemoprevention. This update will focus on a critical
      evaluation of prostate-specific antigen (PSA), percentage of free PSA, and human
      glandular kallikrein-2 (hK2) and how they may be used or misused for
      chemoprevention studies.

PMID- 11295612
TI  - Oxidative stress in chemoprevention trials.
AB  - Prostate cancer continues to be the most frequently diagnosed cancer in men in
      the United States. Despite aggressive intervention, a significant number of men
      with prostate cancer will not be cured of their disease and will face the
      possibility of metastatic disease. Thus, development of potent prevention
      strategies to diminish or eliminate this threat is in order. Cellular exposure to
      chronic oxidative stress may be 1 possible etiologic factor in the development of
      many cancers, including prostate cancer. Oxygen radicals can attack DNA directly
      and result in the accumulation of potentially promutagenic oxidized DNA bases
      such as 8-hydroxydeoxyguanosine. In addition, chronic oxidant stress may also
      result in lipid peroxidation and the subsequent generation of a range of reactive
      products that can damage DNA. Disruption of certain genes may result in cellular
      tolerance to oxidative genomic injury. GSTP1 is an enzyme that helps catalyze the
      conjugation reaction between potentially damaging electrophiles and glutathione.
      Inactivation of GSTP1 has been documented to occur in nearly 100% of human
      prostate cancers; it is also frequently inactivated in prostatic intraepithelial
      neoplasia lesions. This inactivation may leave the cell vulnerable to oxidative
      DNA damage and/or tolerant to accumulation of oxidized DNA base adducts. These
      base adducts can be measured by several quantitative methods, such as gas
      chromatography-mass spectrometry with selected ion monitoring. These
      sophisticated methods can be readily integrated into prostate cancer
      chemoprevention studies of new and developing prevention agents by providing
      quantitative assessment of oxidative DNA damage before and after administration
      of these candidate chemopreventive drugs. The combination of genetic information,
      state-of-the-art assessment tools, and novel agents will allow rational, directed
      prostate cancer chemoprevention studies to be performed and, together, will help
      determine the role of chronic oxidative stress in the carcinogenic process of
      prostate cancer.

PMID- 11295613
TI  - Apoptosis as a biomarker in chemoprevention trials.
AB  - Monitoring apoptosis in histologic samples is becoming increasingly important as
      more effort is applied to the study of therapeutic modulators of cell death in
      tumors. The common methods used to monitor DNA fragmentation and cell morphology
      as markers of apoptosis have their own set of advantages and disadvantages.
      Growing knowledge of the signaling events that occur during cell death has
      established the caspase enzymes as the central executioner proteases of
      apoptosis. The results of caspase activity generate neo-epitopes that occur only
      during apoptosis. Directly monitoring caspase-mediated events as markers of
      apoptosis offers advantages over existing assay methods. Recently, several new
      marker antibodies have been developed that detect active caspase enzymes or the
      products they produce. The possibility of using these new marker antibodies for
      monitoring prostate chemoprevention trials is presented in this review.

PMID- 11295614
TI  - Angiogenesis as a potential biomarker in prostate cancer chemoprevention trials.
AB  - Prostate cancer is a multistep process in which progression rather than
      initiation may be the rate-limiting step. A strong possibility is that prostatic
      intraepithelial neoplasia lesions that switch to angiogenic phenotype eventually
      progress to cancer. However, it is a challenging task to quantitate angiogenesis
      in preneoplastic lesions. A promising approach to measuring angiogenesis involves
      real-time TaqMan polymerase chain reaction to quantitate mRNAs encoding a panel
      of angiogenesis markers. This highly sensitive molecular technique has potential
      for quantitating angiogenesis in clinical settings and can be used as a high
      throughput screening procedure in prostate cancer clinical trials.

PMID- 11295615
TI  - Telomerase activity modulation in the prevention of prostate cancer.
AB  - Telomerase is a ribonucleoprotein that stabilizes chromosomes by maintaining
      their telomeric ends. Although telomerase is normally expressed in reproductive
      tissues, it is virtually absent in most normal somatic tissues. During
      carcinogenesis, cells activate telomerase to protect chromosomal ends from the
      telomere erosion that occurs with replication. Prevention of telomere loss by
      activation of telomerase allows for the cellular immortalization that is a
      characteristic of cancer cells. Recent studies have shown that genetic
      instability arising from critical telomere shortening is a mechanism through
      which cancer cells attain multiple genetic aberrations that characterize a
      malignant clone. Thus, the timing of telomerase activation during carcinogenesis
      is likely to play an important role in modulating the genetic instability that
      determines the malignant phenotype. Earlier activation of telomerase should
      minimize genetic aberrations in neoplastic cells and lead to less aggressive
      tumors, or may prevent carcinogenesis. In this article, we discuss recent data on
      telomerase expression in prostate cancer, propose a model that relates the
      dynamics of telomerase activation to the evolution of different prostatic
      malignancies, and discuss the potential application of telomerase activation as a
      strategy for the prevention of prostate cancer.

PMID- 11295616
TI  - Sequence databases and microarrays as tools for identifying prostate cancer
      biomarkers.
AB  - Identification, acquisition, and assessment of molecular markers that could be
      adopted as surrogate endpoints for evaluating a response to prostate cancer
      intervention strategies is highly desirable. Recent advances in the fields of
      genomics and biotechnology have dramatically increased the quantity and
      accessibility of molecular information that is relevant to the study of prostate
      carcinogenesis. One major advance involves the construction of comprehensive
      databases that archive gene sequences and gene expression data. This information
      is in a format suitable for virtual queries designed to distinguish the molecular
      differences between normal and cancer cells. A second major advance uses robotic
      tools to construct microarrays comprising thousands of distinct genes expressed
      in prostate tissues. Such arrays offer a powerful approach for monitoring the
      expression of thousands of genes simultaneously and provide access for techniques
      designed to assess patterns or "fingerprints" of gene expression that may
      ultimately be used as signatures of response to therapeutic intervention.

PMID- 11295617
TI  - New technologies for biomarker analysis of prostate cancer progression: Laser
      capture microdissection and tissue proteomics.
AB  - The widespread use of serum markers during cancer screenings has led to the
      belief that there may be tumor markers yet to be discovered that offer better
      specificity and sensitivity than prostate-specific antigen (PSA). Proteomics, the
      analysis and characterization of global protein modifications, will add to our
      understanding of gene function and aid in biomarker and/or therapeutic target
      discovery. In the past, most proteomic studies were either performed using tumor
      cell lines or homogenized bulk tissue. Unfortunately, these approaches may not
      accurately reflect molecular events that take place in the actual ductal
      epithelium that change as a consequence of the malignant process. This report
      describes alternative proteomic-based approaches aimed at the identification of
      protein markers in the actual premalignant and frankly malignant epithelium.

PMID- 11295618
TI  - Standardization, analytical validation, and quality control of intermediate
      endpoint biomarkers.
AB  - Standardized processes should be used in the identification and development of
      intermediate endpoint biomarkers (IEB) for the prediction of patient-specific
      disease outcomes. Using our own experiences, we outline some of our standardized
      processes. Using computer-assisted image analysis, we developed a new biomarker
      of genetic instability, termed quantitative nuclear grade (QNG). The QNG
      biomarker is derived using nuclear images analyzed from the tumor areas of
      Feulgen-stained 5-microm biopsy or radical prostatectomy tissue sections. From
      the variances of 41 to 60 different nuclear size, shape, and chromatin
      organization features, a QNG solution is computed using either logistic
      regression or artificial neural networks. QNG can then be used as an input for
      models that solve for a patient-specific probability to accurately predict
      disease outcomes. Preoperatively, QNG predicted both the pathologic stage and
      progression of prostate cancer using biopsies (P <0.0001). Postoperatively, QNG
      proved extremely valuable in the prediction of biochemical progression using
      radical prostatectomy specimens with more than 10 years of follow-up (P <0.0001).
      We also demonstrate the identification of novel, differentially expressed,
      prostate cancer genes using RNA fingerprinting methods and the clinical utility
      of testing for these genes in both blood and tissue samples. Also illustrated is
      the improvement of serum biomarker performance by combining molecular forms of
      PSA with new biomarkers. In conclusion, the development of new IEBs requires
      planning based upon an understanding of the molecular pathogenesis of disease.
      IEB selection and clinical evaluation should employ standardized methods of
      testing and validation, followed by publication. QNG is 1 example of a new,
      highly predictive, IEB for prostate cancer that has been developed using these
      processes.

PMID- 11295619
TI  - Potential target populations and clinical models for testing chemopreventive
      agents.
AB  - Target populations for chemoprevention trials should include those at higher than
      average risk for the development of prostate cancer as defined by explicit
      epidemiologic and genetic criteria. Such populations include a "primary
      prevention" group without histologic or clinical evidence of cancer, and several
      clinical models of "secondary prevention," including those with clinically
      evident disease prior to definitive therapy and those at high risk of recurrence
      after therapy based on histological or biochemical status. Each risk group and
      clinical model has potential advantages and disadvantages, and the mechanisms
      that underlie disease development and progression in each group may be unique.
      These observations give rise to many potential clinical trials of specific
      agents. These trials should also include collection of data on potentially
      confounding influences on disease development and progression.

PMID- 11295620
TI  - Prostate-specific antigen-enhanced testing and risk stratification for
      chemoprevention trials.
AB  - Prostate-specific antigen (PSA) testing could be used to identify men who are at
      higher future risk of developing clinical prostate cancer or to diagnose prostate
      cancer earlier in high-risk groups, such as black men or those with a family
      history of the disease. These cohorts then could be offered chemopreventive
      clinical trial participation opportunities. The Physicians' Health Study and
      other longitudinal studies have shown that even between a PSA level of 1.0 and
      4.0 ng/mL, the risk of future prostate cancer is incrementally increased.
      Department of Defense Studies of young men between 15 and 45 show that normal men
      have very low PSA values. Using a threshold PSA even as low as 1.5 ng/mL for men
      in their fifth decade is well beyond the 95th percentile of "normal" PSA. Young
      black men between 40 and 49 years old have a higher risk of prostate cancer than
      white men and should be pursued for chemoprevention studies. PSA is not perfect.
      Benign prostatic hyperplasia and inflammation (and, perhaps, other factors) can
      confound the use of PSA thresholds to identify men for chemoprevention or early
      detection. Certain chemopreventive agents may affect PSA physiology without
      affecting the disease process itself creating a meaningless epiphenomenon. Young
      black men may not generally be receptive to PSA testing or chemopreventive
      trials.

PMID- 11295621
TI  - African American men and hereditary/familial prostate cancer: Intermediate-risk
      populations for chemoprevention trials.
AB  - The risk of prostate cancer diagnosis among African Americans is 66% greater than
      among European American men. For African Americans with a family history of
      hereditary prostate cancer the increased risk of diagnosis is even greater. Thus,
      this population should be a prime target for chemoprevention strategies. In
      addition to the higher incidence of prostate cancer among African Americans
      compared with other populations, the mortality of prostate cancer among this high
      risk population is significantly greater than 100% compared with other
      populations, thus further demonstrating the need for chemoprevention in this
      target population. Autopsy studies and clinical findings support the argument
      that prostate cancer exhibits more aggressive biological behavior and perhaps
      more rapid growth among African Americans compared with European Americans. It is
      hypothesized that genetic and epigenetic factors may be responsible for a more
      rapid growth rate among African Americans compared with other populations.
      Accumulating evidence indicates that a diet high in fat content is closely
      associated with prostate cancer progression. Investigators have reported that fat
      intake and percentage of energy from fat were highest in African Americans,
      followed by European Americans, Japanese Americans, and Chinese Americans. In
      conclusion, African Americans are an important target population to include in
      chemoprevention trials that include dietary factors as preventive agents.

PMID- 11295622
TI  - A randomized, controlled chemoprevention trial of selenium in familial prostate
      cancer: Rationale, recruitment, and design issues.
AB  - Deficiencies of selenium have been associated with an increased cancer risk, and
      several clinical and animal trials have suggested that improved selenium
      nutrition may reduce the incidence of several kinds of cancer, including lung,
      colorectal, and breast. Results from recent trials also show an anticarcinogenic
      effect of selenium in the prostate. There is converging evidence from
      epidemiologic, experimental animal, and molecular biology studies for an
      antitumor effect of selenium. Evidence suggests there are two modes of action of
      selenium affecting cancer risk: first, by functioning as an essential nutrient
      that provides the catalytic centers of a number of selenoenzymes, including some
      with antioxidant and redox functions; second, by serving as a source of selenium
      metabolytes that affect carcinogenesis in other ways. The first mechanism appears
      most relevant to protection against cancer initiation, the second against cancer
      progression. There is conclusive evidence of the increased risk of prostate
      cancer for a male with a family history of the disease. As a result of this
      evidence, and the evidence supporting the chemopreventive properties of selenium,
      this study proposed that a trial to test the effect of selenium on men at high
      risk for development of prostate cancer is appropriate. This article describes
      the Australian Prostate Cancer Prevention Trial Using Selenium (APPOSE) trial to
      test the hypothesis that daily dietary supplementation with selenium will reduce
      prostate cancer incidence in a population of men who are at increased risk
      because of a first-degree relative with prostate cancer.

PMID- 11295623
TI  - Randomized, controlled chemoprevention trials in populations at very high risk
      for prostate cancer: Elevated prostate-specific antigen and high-grade prostatic
      intraepithelial neoplasia.
AB  - This is a report of research efforts underway at the Arizona Cancer Center. These
      efforts build upon Larry Clark's unanticipated clinical prevention trial results:
      those results indicated that 200 microg/day of selenium in selenized yeast
      decreased prostate cancer risk by almost 60%. The trials underway address various
      phases of the possible preventive activity of selenium. The first of these, for
      men who are suspected to have prostate cancer but who have had a biopsy revealing
      no evidence of cancer, will test the ability of selenium to prevent the
      development of clinical prostate cancer. The second is for men with high-grade
      prostatic intraepithelial neoplasia; the trial will test whether selenium will
      prevent the development of prostatic cancer in this high-risk group. The third
      trial is for men who have been diagnosed with prostate cancer and are scheduled
      for prostatectomy: the trial is designed to test whether evidence of selenium
      linked changes can be identified in the tissue removed at prostatectomy. The
      fourth trial is for men who have been diagnosed with prostate cancer but who have
      chosen neither surgery nor irradiation; this trial will evaluate whether
      treatment with selenium will inhibit the progress of prostate cancer. Together,
      these trials will provide important information as to the prostate cancer
      chemopreventive potential of selenium.

PMID- 11295624
TI  - Chemoprevention for prostatic carcinoma: The role of flutamide in patients with
      prostatic intraepithelial neoplasia.
AB  - High-grade prostatic intraepithelial neoplasia (HGPIN) is believed to be a
      precursor for prostatic adenocarcinoma. The prevalence of prostatic
      intraepithelial neoplasia (PIN) increases with advancing age. Autopsy studies
      suggest that PIN may precede the development of prostatic adenocarcinoma by up to
      10 years. As such, HGPIN is believed to be a marker of increased risk. This
      provides a potential opportunity for chemoprevention. Flutamide is 1 agent with
      potential activity and limited side effects that may act to prevent or delay the
      onset of prostatic adenocarcinoma in men with HGPIN. A clinical trial is
      currently underway to assess the efficacy of flutamide.

PMID- 11295625
TI  - The role of prostate needle biopsy in evaluation of chemopreventive agents.
AB  - Needle biopsy of the prostate safely furnishes tissue that can be studied for the
      effects of promising chemopreventive agents on biomarkers. The modulation of
      biomarkers, such as those for apoptosis (TUNEL, Bcl-2, or nuclear morphometry),
      angiogenesis (factor 8), and cell proliferation (Ki-67), can indicate the
      potential of a new agent without waiting for the definitive evaluation of
      traditional endpoints, such as reduction in cancer mortality. A recent
      modification of prostate biopsy technique, including additional cores taken from
      the lateral peripheral zone, may improve the cancer yield by as much as 35%
      without increasing major complications, facilitating serial in vivo tests on
      cancer tissue. The serial biopsy approach may be especially valuable in "watchful
      waiting" cohorts.

PMID- 11295626
TI  - Preprostatectomy: A clinical model to study stromal-epithelial interactions.
AB  - The preprostatectomy setting serves as a valuable clinical model for early
      developmental clinical trials for evaluating promising agents for
      chemoprevention. In the preprostatectomy model, study agents are administered
      between the diagnostic biopsy for prostate cancer and definitive therapy. The
      prostatic tissue that is available after prostatectomy allows for biomarker
      evaluation of all the components of the prostate, including the glandular
      epithelium, blood vessels, and the stroma. This provides an opportunity to study
      the reciprocal interactions between the stroma and the epithelium. Morphologic
      studies suggest that prostatic stromal cells play a critical role in affecting
      the growth and maturation of prostatic epithelium. Experimental studies in tissue
      culture show that carcinoma-associated stromal cells can promote prostatic
      carcinogenesis, and normal stromal cells may be able to inhibit prostatic
      carcinogenesis by inducing differentiation and decreasing the proliferation of
      the epithelium. Although the complex molecular mechanisms through which stroma
      modulates the epithelial cell phenotype remain to be elucidated, there are
      several well-characterized signaling pathways, such as for growth factors and
      steroid hormones, that are likely to contribute to the modulation of transformed
      epithelial cells. There is evidence of an association between increased serum
      levels of IGF-I and an increased risk of prostate cancer. The IGF system appears
      to play an important role in the development of prostate cancer by modulation of
      paracrine pathways, and also by modulation of the concentrations of different
      stromal and epithelial IGFBP, which are differentially expressed in the
      epithelium and stroma. Nerve growth factor is capable of stimulating a
      proliferative response via a high affinity Trk receptor present in normal and
      malignant prostate epithelia, and alternatively can mediate apoptosis via the low
      affinity p75NTR receptor that is progressively lost from the malignant prostate.
      As the role of each stromal element involved in carcinogenesis becomes further
      defined, these elements offer promising targets for new chemopreventive
      strategies.

PMID- 11295627
TI  - Dietary trial in prostate cancer: Early experience and implications for clinical
      trial design.
AB  - Much epidemiologic and case-controlled evidence suggests that diet may be a
      modifier of prostate cancer risk. However, the role of dietary modification in
      men known to have prostate cancer is a matter of some debate. To elucidate the
      effect of diet and comprehensive lifestyle changes on cancer risk, we are
      conducting a randomized, prospective clinical trial on men with clinically
      localized prostate cancer who have selected "watchful waiting" as primary
      therapy. Since its inception in April 1997, 93 men have been randomized to
      control (n = 47) or dietary and lifestyle intervention (n = 46). Patients in the
      intervention group are asked to eat a low-fat, soy-supplemented vegan diet and
      take part in stress management, psychosocial group support, and exercise
      programs. After 1 year, adherence to all four interventions was greater than 80%,
      and no deaths or adverse outcomes have occurred. To date, we have collected
      prostate-specific antigen and endorectal magnetic resonance imaging and
      spectroscopy data on 63 patients (34 control and 29 intervention). This study
      demonstrates that a randomized, prospective dietary trial for men with localized
      prostate cancer is safe and feasible. The methodologies used provide insights
      into practical aspects of diet design and compliance assessment that may be
      useful templates for future dietary trials.

PMID- 11295628
TI  - Chemoprevention trials in men with prostate-specific antigen failure or at high
      risk for recurrence after radical prostatectomy: Application to efficacy
      assessment of soy protein.
AB  - This article discusses the basic elements of chemoprevention trial designs using
      cohorts of men following radical prostatectomy who either have prostate-specific
      antigen (PSA) failure indicative of recurrence or are at high risk for recurrence
      (positive surgical margins, extracapsular extension, seminal vesicle invasion,
      positive lymph nodes, Gleason score of greater than or equal to 8, preoperative
      serum PSA less than 20 ng/mL). Two ongoing randomized, double-blind, placebo
      controlled clinical trials with soy protein as intervention in these 2
      populations are described. In the trial with men at high risk for recurrence,
      participants started intervention within 4 months after surgery and were followed
      for up to 2 years; primary endpoints were PSA failure rate and time-to-PSA
      failure. In the trial with men with PSA failure (PSA 0.1 to 2.0 ng/mL),
      participants received treatment for 8 months and the primary endpoint is rise in
      PSA over time. The strengths and limitations of these designs are discussed and
      interim experience using studies with soy protein as the intervention agent are
      summarized.

PMID- 11295629
TI  - Design considerations for efficient prostate cancer chemoprevention trials.
AB  - Prostate cancer, even with its substantial public health impact of 180,400 new
      cases and 31,900 deaths estimated for 2000, still has a very low annual incidence
      (0.27% for men 34.4 years and older), which makes designing and conducting
      efficient prostate cancer prevention trials a challenge. Definitive prevention
      trials with cancer endpoints, such as the Breast Cancer Prevention Trial (BCPT),
      Prostate Cancer Prevention Trial (PCPT), and Selenium and Vitamin E Cancer
      Prevention Trial (SELECT), require long trial duration (up to 12 years) and large
      sample size (up to 32,400 subjects) to accomplish their objectives. This article
      discusses design concepts for potential prostate cancer prevention trials that
      require fewer years, subjects, and resources to complete. Design elements, such
      as high-risk populations, randomization, surrogate endpoints, including quality
      of-life endpoints, masking/blinding, and various clinical/statistical designs
      (including 1-way layout, all-versus-none, factorial, and adaptive designs), are
      discussed, along with the ultimate goal of gaining US Food and Drug
      Administration approval for prostate-cancer preventive agents that can improve
      public health by reducing prostate cancer incidence and mortality.

PMID- 11295630
TI  - Trial endpoints for drug approval in oncology: Chemoprevention.
AB  - As with other drugs, new drug applications for marketing approval of
      chemopreventive drugs must include data from adequate and well-controlled
      clinical trials that demonstrate effectiveness and safety for the intended use.
      This article summarizes the regulatory requirements for traditional marketing
      approval, as well as for approval under the accelerated approval regulations.
      Unlike traditional approval, accelerated approval is based on a surrogate
      endpoint that is reasonably likely to predict clinical benefit. Discussions with
      the Food and Drug Administration (FDA) regarding the validity of trial endpoints
      that may serve as surrogates for clinical benefit for accelerated approval should
      take place as early as possible in drug development. Meetings with the FDA to
      discuss these issues may be requested throughout the clinical development of a
      new drug.

PMID- 11295631
TI  - Early clinical trials of chemopreventive and biologic agents: Designs,
      populations, and endpoints.
AB  - The optimal design for initial clinical trials of chemopreventive agents for
      cancer has not been determined. A single design is unlikely to be the model for
      chemoprevention of cancer, even for prevention of a single subtype of cancer,
      because of the heterogeneity of drugs under investigation and the variety of
      biologic effects being targeted. Factors that are important in designing initial
      clinical trials include the proposed mechanisms of drug action, the ability and
      types of assays available to detect that activity or pharmacodynamic effect, and
      the extent of prior clinical experience. In this article, we present a discussion
      of the factors to be considered in initial activity studies, followed by a
      specific example of early clinical assessment of a noncytotoxic agent (R
      flurbiprofen, E-7869) as a potential chemopreventive agent for prostate cancer.

PMID- 11295632
TI  - Bayesian monitoring of a phase 2 chemoprevention trial in high-risk cohorts for
      prostate cancer.
AB  - The objective of phase 2 cancer chemoprevention trials is to evaluate whether a
      chemopreventive agent will cause significant modulation of intermediate endpoint
      biomarkers (IEB) in patients at high risk for the disease. A phase 2
      chemoprevention trial of 4-hydroxyphenyl retinamide (4-HPR) versus placebo was
      conducted in men with a histologic diagnosis of early prostate cancer and
      scheduled to have radical prostatectomy. A Bayesian monitoring method was used to
      sequentially monitor this trial for evidence of biological activity or
      ineffectiveness based on a single IEB variable. Different prior distributions
      were used and posterior distributions were obtained to calculate the probability
      that treatment differences are greater than or less than a predetermined
      clinically significant effect. The interim analysis of transforming growth factor
      alpha expression indicated a high probability of insufficient biological activity
      of 4-HPR on this IEB. This study demonstrates the potential utility of Bayesian
      methods in the decision-making process in the conduct of phase 2 chemoprevention
      trials.

PMID- 11295633
TI  - Prostate cancer chemoprevention: Strategies for designing efficient clinical
      trials.
AB  - A chemoprevention (CP) strategy has evolved for conducting efficient clinical
      trials for prostate cancer (PCa) prevention. It integrates five key components,
      including agents, biomarkers, cohorts, designs, and endpoints. The rationale for
      the CP strategy relates to the natural history of prostate cancer. There is a
      wide array of natural and synthetic agents that hold promise for inhibiting,
      reversing, or modulating the transition from normal to precancer and from
      precancer to cancer. These agent classes include antiandrogens, antiestrogens,
      phytoestrogens, antioxidants, anti-inflammatory (proapoptotic) agents,
      antiproliferation/antidifferentiation agents, signal transduction modulators of
      receptor tyrosine kinase and ras farnesylation, antiangiogenesis agents,
      insulinlike growth factor (IGF)-1, peroxisome proliferator-activator receptor
      modulators (-gamma and -delta), and gene-based interventions. Biomarkers and
      endpoints are guided by the level of evidence required (eg, phase 1, 2, 3). Two
      candidate surrogate endpoints (SE) based on histology are high-grade prostatic
      intraepithelial neoplasia (HGPIN) and computer-assisted image analysis of
      dysplastic lesions. Phase 1 trials use standard endpoints of safety,
      pharmacokinetics and limited pharmacodynamics. Phase 2 trials use endpoints of
      modulation of biomarkers and correlation with histology. Phase 3 trials use
      endpoints of clinical benefit, such as cancer incidence reduction and quality of
      life. Validation of a biomarker as a SE involves correlation of the biomarker
      with clinical benefit. Cohorts (target populations) for phase 2/3 trials include
      the general population of men over age 50 with a normal prostate-specific antigen
      (PSA), subjects with a strong family history of PCa, subjects with elevated
      PSA/negative biopsy, and subjects with HGPIN/negative biopsy. These at-risk
      populations reflect key individual risk factors (age, race, serum PSA
      [free/total]; serum IGF-1/IGF binding protein (IGFBP)-3; 1, 25(OH)(2) D3; family
      history of PCa; carriers of PCa susceptibility genes [ELAC2, CYP3A4, SRD5A2,
      etc.]; and histology such as atypia and HGPIN) that could be combined into a
      multivariate risk model for PCa. The probability of cancer risk (recurrence) is a
      key factor that impacts on the clinical trial design (power, sample size, and
      primary endpoint). Multivariate predictive mathematical models for biochemical
      recurrence after radical prostatectomy by decreasing sample size and time to
      clinical outcomes maximize trial efficiency and identify the patients most likely
      to benefit from secondary prevention. The two large primary prevention trials,
      Prostate Cancer Prevention Trial/Seleninium and Vitamin E Chemoprevention Trial
      (PCPT/ SELECT), in low- and average-risk subjects have sample sizes of 18,000 to
      32,000, with a treatment duration of 7 years to detect a 25% reduction in biopsy
      proven PCa. Subjects with HGPIN have the highest known cancer risk (approximately
      50% at 3 years), and thus require a small sample size (n = 450) to detect a 33%
      reduction in cancer incidence. A schema involving three sequential trials for
      agent registration is described. In summary, a CP strategy that incorporates well
      defined agents, clinical and validated SE, and high-risk cohorts defined by
      genetic and acquired risk factors in a series of well-designed randomized
      controlled trials provides an efficient pathway for evaluating and approving new
      agents for PCa prevention.

PMID- 11295634
TI  - The Prostate Cancer Prevention Trial: Current status and lessons learned.
AB  - The Prostate Cancer Prevention Trial is the first phase 3 prevention trial for
      prostate cancer in the United States. The implementation of a large, randomized
      trial has provided a wealth of information that will aid in future cancer
      chemopreventive studies in US men. The experience from the implementation of the
      Prostate Cancer Prevention Trial was reviewed. Lessons learned from the study
      include: (1) US men are willing to enroll in prevention trials; (2) participants
      in chemoprevention trials are well educated and healthy; (3) the successful
      cancer prevention trial is viewed by participants as a "men's health trial"; (4)
      data management and discipline coordination at participating institutions are
      critical; (5) study design change is commonly required owing to changes in
      clinical practice over the course of the trial; and (6) training of institutional
      staff is essential. With proper design, robust data management, and a flexible
      staff, large-scale randomized chemoprevention trials can be accomplished in the
      United States. With the extraordinary number of potential agents, it is expected
      that much will be accomplished with this strategy in the near future.

PMID- 11295635
TI  - Quality of Life endpoints in prostate chemoprevention trials.
AB  - Although the ultimate goal of any chemoprevention study is to extend life by
      preventing cancer, it is also important that in doing so, the quality of life is
      not reduced. Hence, quality of life (QOL) endpoints are secondary only in
      importance to survival as an endpoint for prostate chemoprevention trials. One
      can conceptualize QOL endpoints as just another surrogate endpoint biomarker. QOL
      can be administered and collected in a valid and reliable fashion from cancer
      patients as demonstrated by numerous clinical trials. To date more than 25
      prostate cancer QOL tools have been developed with over 700 different items.
      However, patients may be asymptomatic, leaving the sensitivity and specificity of
      the QOL instrumentation in question. Judicious use of a global QOL measure
      supplemented by protocol-specific or disease-specific instruments is an efficient
      approach for prostate chemoprevention trials. Clinical significance and missing
      data considerations need to be elucidated a priori in definitive terms so that
      results are directly interpretable from the data obtained. The effect of
      chemopreventive agents on QOL needs to be sufficiently modest to be practical to
      justify administration in a healthy population. As such, great care needs to be
      given to a priori determination of the QOL constructs that are most likely to
      change.

PMID- 11295636
TI  - Validation of surrogate endpoint biomarkers in prostate cancer chemoprevention
      trials.
AB  - Phase 2 cancer chemoprevention trials are designed to provide estimates of the
      efficacy of an agent at a specified dose, and the expected size of the risk
      reduction that may be achieved in a subsequent phase 3 randomized trial. To allow
      these trials to be rapid and efficient, the study outcome is modulation of a
      surrogate endpoint biomarker (SEB), that is, a molecular event assumed to be on
      the causal pathway between the chemopreventive agent and the desired reduction in
      cancer incidence. However, SEBs commonly used in prostate cancer chemoprevention
      studies, such as prostate-specific antigen, high grade prostatic intraepithelial
      neoplasia, proliferation, and apoptosis, have not been validated by documenting
      that changes in the SEBs ultimately translate to decreased prostate cancer risk.
      Because of uncertainty in the pathway from SEBs to cancer, additional
      considerations are necessary to permit valid inferences from phase 2 trial data.
      This article considers the framework underlying validation and use of SEBs in
      specific chemoprevention models and methodologic issues in quantifying the effect
      of an agent. In particular, inferences depend on whether a single pathway
      involving the SEBs is assumed to mediate the effect of the agent on cancer
      incidence. If there are competing pathways of equal or greater importance than
      the one involving the candidate SEB, then the estimate of chemopreventive
      efficacy will be biased and may greatly underestimate the magnitude of the
      achievable risk reduction. Strategies for validating biomarkers and minimizing
      the degree of bias in the risk reduction estimate are discussed. Finally,
      problems associated with phase 2 study designs commonly used for prostate cancer
      chemoprevention are discussed, along with possible solutions.

PMID- 11295638
TI  - Optical mapping approaches to cardiac electrophysiological functions.
AB  - Recently, optical methods for monitoring membrane potential with fast voltage
      sensitive dyes have been introduced as a powerful tool for studying cardiac
      electrical functions. These methods offer two principal advantages over more
      conventional electrophysiological techniques. One is that optical recordings may
      be made from very small cells that are inaccessible to microelectrode impalement,
      and the other is that multiple sites/regions of a preparation can be monitored
      simultaneously to provide spatially resolved mapping of electrical activity. The
      former has made it possible to record spontaneous electrical activities in early
      embryonic precontractile hearts, and the latter has been applied for mapping of
      the propagation patterns of electrical activities in the cardiac tissue. In this
      article, optical studies of the electrophysiological function of the vertebrate
      heart are reviewed.

PMID- 11295640
TI  - Childhood risk factors for atopy and the importance of early intervention.
AB  - The increasing prevalence of atopic diseases, particularly atopy-associated
      asthma, has become a major challenge for allergists and public health authorities
      in many countries. The understanding of the natural history of the atopic march,
      including the determinants that are modifiable and might become candidates for
      preventive intervention, is still very limited. Information provided by cross
      sectional studies can only generate hypotheses, which need to be supported by
      prospective, longitudinal, cohort studies. Ultimately, it will depend on the
      results of well-controlled intervention studies to identify which nutritional,
      environmental, or lifestyle-related factors should be considered for early
      intervention and might be useful to reverse the epidemiologic trend.

PMID- 11295641
TI  - Role of IL-9 in the pathophysiology of allergic diseases.
AB  - Considerable evidence from both human and animal studies indicates that CD4(+)
      cells are the predominant cell type involved in the regulation of airway
      inflammation through the expression of T(H)2-type cytokines. The effects of T(H)2
      type cytokines, particularly IL-4 and IL-5, on inflammatory and structural cells
      in airways have been studied in great detail. They were shown to be important for
      inflammatory cell maturation, activation and proliferation, IgE production,
      chemokine expression, mucus secretion, and bronchial hyperresponsiveness. Recent
      work has shown the potential importance of another T(H)2-type cytokine, IL-9. The
      development of transgenic mice overexpressing IL-9 has suggested a key role for
      this cytokine in the development of the asthmatic phenotype, including
      eosinophilic inflammation, bronchial hyperresponsiveness, elevated IgE levels,
      and increased mucus secretion. IL-9 has been shown to act on many cell types
      involved in asthma, including T cells, B cells, mast cells, eosinophils,
      neutrophils, and epithelial cells, and thus might be important in the
      pathophysiology of allergic asthma.

PMID- 11295642
TI  - Can medical surveillance measures improve the outcome of occupational asthma?

PMID- 11295643
TI  - TH2 cytokine-associated transcription factors in atopic and nonatopic asthma:
      evidence for differential signal transducer and activator of transcription 6
      expression.
AB  - BACKGROUND: The expression of IL-4 and IL-5 is increased in patients with atopic
      asthma compared with control subjects and correlates with indices of pulmonary
      function. In nonatopic asthma the expression of IL-4, unlike IL-5, fails to
      correlate with pulmonary function, and compared with their atopic counterparts,
      these patients have fewer cells expressing IL-4 receptor (IL-4R). As such, a
      deficiency in the IL-4 signaling pathway may be implicated in nonatopic asthma.
      The transcription factors GATA-3 and cMAF mediate IL-4 and IL-5 synthesis,
      whereas signal transducer and activator of transcription 6 (STAT-6) is critical
      for IL-4R signaling. OBJECTIVE: This study examines the expression profile of
      these transcription factors in asthma, according to atopic status. METHODS: With
      immunocytochemistry, the expression of GATA-3, cMAF, and STAT-6 protein was
      determined in sections of bronchial biopsy specimens from patients with atopic
      asthma (n = 7), patients with nonatopic asthma (n = 8), and control subjects (n =
      8). RESULTS: Higher numbers of cells expressing GATA-3 and cMAF were observed in
      patients with atopic and those with nonatopic asthma than in control subjects and
      patients with tuberculosis (P <.001). There were also more STAT-6-immunoreactive
      cells in patients with atopic and those with nonatopic asthma than in control
      subjects (P <.0001, P <.05). Notably, however, fewer cells expressing STAT-6
      protein were observed in nonatopic versus atopic asthma (P <.0001). CONCLUSIONS:
      These results demonstrate the upregulation of GATA-3 and cMAF in both variants of
      asthma and indicate that reduced IL-4R signaling, because of lower STAT-6
      expression, may be a feature of nonatopic asthma.

PMID- 11295644
TI  - The 30th anniversary of the American Board of Allergy and Immunology: then and
      now.
AB  - Thirty years ago the Allergy Subspecialty Boards of the American Board of
      Pediatrics (ABP) and the American Board of Internal Medicine (ABIM) merged to
      form the American Board of Allergy and Immunology (ABAI). The ABAI mission was
      to: establish qualifications and examine physician candidates for certification
      as specialists in allergy and immunology; serve the public, physicians,
      hospitals, and medical schools by providing the names of physicians certified by
      the Board; assist educational and professional organizations to improve the
      quality of care and availability of allergists to deliver such care, to establish
      and improve standards for the teaching of allergy and immunology, to establish
      standards for training programs, and to encourage development of increased
      opportunities for training of physicians interested in allergy and immunology.
      This mission statement has guided the activities of the Board ever since by
      providing a strong focus on the 2 major responsibilities: examining and
      certifying candidates in a fair objective way, and setting standards for the
      content and conduct of training programs.

PMID- 11295645
TI  - A link between chronic asthma and chronic infection.
AB  - BACKGROUND: Asthma is a prevalent disease with marked effects on quality of life
      and economic societal burden. However, the cause of asthma and its
      pathophysiology are not completely defined. Recently, the possibility that
      chronic infection may play a role has been suggested. OBJECTIVE: We sought to
      define the association between Mycoplasma and Chlamydia species and chronic
      asthma. METHODS: We performed a comparison study of asthmatic patients and normal
      control subjects. Fifty-five patients with chronic stable asthma were compared
      with 11 normal control subjects by using PCR, culture, and serology for
      Mycoplasma species, Chlamydia species, and viruses from the nasopharynx, lung,
      and blood. Bronchoalveolar lavage cell count and differential, as well as tissue
      morphometry, were also evaluated. Computer-generated scoring for the degree of
      chronic sinusitis in asthmatic patients was additionally evaluated. RESULTS:
      Thirty-one of 55 asthmatic patients had positive PCR results for Mycoplasma (n =
      25) or Chlamydia species (n = 6), which were mainly found on lung biopsy
      specimens or in lavage fluid. Only 1 of 11 normal control subjects had positive
      PCR results for Mycoplasma species. The distinguishing phenotype between
      asthmatic patients with positive and negative PCR results was the significantly
      greater number of tissue mast cells in the group with positive results.
      CONCLUSION: A significant number of patients with chronic stable asthma
      demonstrate the presence of Mycoplasma species, Chlamydia species, or both in
      their airways, with the distinguishing feature of increased mast cell number.
      These findings need further delineation but may help us to understand the
      pathophysiology of asthma and new treatment options.

PMID- 11295646
TI  - IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma.
AB  - BACKGROUND: IL-4 and IL-13 have been shown to be critical for expression of the
      asthma phenotype in a murine model and may modulate human fibroblast function.
      OBJECTIVE: We hypothesized that IL-4 and IL-13 would increase airway fibroblast
      proliferation and reduce the ability of dexamethasone to decrease this
      proliferation. METHODS: Six subjects with severe asthma, 5 subjects with mild
      asthma, and 5 healthy subjects underwent bronchoscopy with endobronchial biopsy.
      Biopsy specimens were placed in Dulbecco modified Eagle medium and cultured, and
      only fibro-blasts from the first and second passages were evaluated. Cells were
      incubated with IL-4 (50 ng/mL), IL-13 (10 ng/mL), and the combination for 48
      hours in the presence and absence of dexamethasone, 10(-7) mol/L, and 10(-8)
      mol/L. Fibroblasts were also incubated with IFN-gamma at 50 ng/mL to assess the
      response of a T(H)1 cytokine on proliferation. RESULTS: Fibroblast proliferation,
      determined by (3)H-thymidine incorporation, was significantly increased by IL-4
      in subjects with mild asthma as compared with IL-4 in subjects with severe asthma
      and healthy subjects (P =.003), IL-13 (P =.011), and the combination (P =.004).
      Dexamethasone also increased proliferation in the group with mild asthma as
      compared with the group with severe asthma and the healthy group (10(-7) mol/L, P
      =.02; 10(-8) mol/L, P =.02). IFN-gamma did not significantly alter airway
      fibroblast proliferation. CONCLUSION: IL-4, IL-13, and dexamethasone all
      significantly increased fibroblast proliferation in subjects with mild asthma.

PMID- 11295647
TI  - Total and specific IgE in nasal polyps is related to local eosinophilic
      inflammation.
AB  - BACKGROUND: Nasal polyps (NPs) are characterized by eosinophilic inflammation and
      often coexist with asthma. However, the role of atopy and IgE in NP pathogenesis
      is unclear. OBJECTIVE: We sought to determine whether there is an association
      between total and specific IgE to a variety of allergens in polyp and nonpolyp
      tissue and markers of eosinophilic inflammation or skin test results. METHODS:
      Homogenates were prepared from nasal tissue of 20 patients with NPs and 20
      patients without NPs and analyzed for concentrations of IL-5, IL-4, eotaxin,
      leukotriene (LT) C4/D4/E4, sCD23, and histamine (ELISA). Eosinophil cationic
      protein (ECP), tryptase, and total and specific IgE for inhalant allergens and
      Staphylococcus aureus enterotoxins were measured (ImmunoCAP). RESULTS: The
      concentrations of total IgE, IL-5, eotaxin, ECP, LTC4/D4/E4, and sCD23 were
      significantly higher in NP tissue compared with nonpolyp tissue. Total IgE was
      significantly correlated to IL-5, ECP, LTC4/D4/E4, and sCD23 and to the number of
      eosinophils in NPs. On the basis of the presence of specific IgE antibodies in
      tissue, 3 NP groups were defined. NP group 1 demonstrated no measurable specific
      IgE, and NP group 2 selected specific IgE. The third group demonstrated a
      multiclonal specific IgE, including IgE to S aureus enterotoxins, a high total
      IgE level, and a high prevalence of asthma. CONCLUSIONS: These studies suggest
      that there is an association between increased levels of total IgE, specific IgE,
      and eosinophilic inflammation in NPs, which may be of relevance in the
      pathophysiology of nasal polyposis. Similarly, the presence of specific IgE to
      staphylococcal enterotoxins A and B also points to a possible role of bacterial
      superantigens.

PMID- 11295648
TI  - Association of specific allergen sensitization with socioeconomic factors and
      allergic disease in a population of Boston women.
AB  - BACKGROUND: Socioeconomic differences in allergic disease prevalence have been
      reported; asthma has been associated with poverty in the United States and hay
      fever and eczema with relative affluence elsewhere. It is not yet established to
      what degree such differences in disease prevalence reflect patterns of
      sensitization and specific allergen sensitivities. OBJECTIVE: We analyzed
      specific and total IgE measurements in a sample of 458 women, enriched for
      allergic disease, from the metropolitan Boston area to establish the relation of
      allergen sensitization to markers of socioeconomic status (SES) and to the
      prevalence and socioeconomic pattern of allergic disease in this community.
      METHODS: Total and specific IgE antibodies were measured with the UNICAP System;
      self-reported allergic disease, household income, education, and race-ethnicity
      were ascertained with a questionnaire; and a further marker of poverty
      (percentage living below the poverty level) in the women's area of residence was
      established on the basis of zip codes. Analysis was performed with SAS
      statistical software. RESULTS: Markers of low SES were univariately associated
      with increases in total IgE, number of allergen sensitizations, and levels of
      specific IgE. Socioeconomic differences in sensitization to cockroach (35% vs 6%
      in the highest and lowest poverty areas), animal (44% vs 26%), and ragweed (49%
      vs 23%) allergens were most marked. Sensitization primarily to indoor inhalant
      allergens (not ragweed or ryegrass) were associated with an increased risk of
      asthma, even after adjustment for SES. CONCLUSION: We have demonstrated a
      socioeconomic gradient in sensitization that concords with increased rates of
      asthma in less affluent communities in this population.

PMID- 11295649
TI  - Elevated secretion of myeloperoxidase by neutrophils from asthmatic patients: the
      effect of immunotherapy.
AB  - BACKGROUND: There is increasing evidence of neutrophil participation in asthma
      and the allergic process. After activation, neutrophils release myeloperoxidase
      (MPO) together with other granule enzymes. OBJECTIVES: In this study we attempted
      to evaluate the release of MPO in vitro by neutrophils from asthmatic patients
      and the relationship between neutrophil degranulation and lung function, measured
      as FEV(1), of the patients. We also investigated the possible role of
      immunotherapy in the release of MPO by neutrophils. METHODS: Neutrophils were
      stimulated with formyl-methionyl-leucyl-phenylalanine for 45 minutes at 37
      degrees C. MPO released from neutrophils was assayed by using an MPO enzyme
      immunoassay. RESULTS: Neutrophils released statistically significantly higher MPO
      levels in the asthmatic patients not receiving immunotherapy than in the healthy
      group. A significant inverse correlation was observed in the asthmatic group not
      receiving immunotherapy between MPO secretion and lung function, measured as
      FEV(1), of the patients. Neutrophils of the asthmatic group receiving
      immunotherapy released significantly less MPO than did those of the asthmatic
      group not receiving immunotherapy, with MPO levels equal to those from
      nonallergic subjects. CONCLUSIONS: We conclude that neutrophils obtained from
      allergic asthmatic patients have an increased propensity to release MPO. The
      experiments described here provide evidence that there is a significant inverse
      relationship between levels of MPO released by neutrophils from allergic patients
      and lung function, as assessed by FEV(1). Our study suggests that immunotherapy
      actively modifies the release of MPO in vitro by neutrophils from allergic
      asthmatic patients.

PMID- 11295650
TI  - Fluticasone propionate aqueous nasal spray reduces inflammatory cells in
      unchallenged allergic nasal mucosa: effects of single allergen challenge.
AB  - BACKGROUND: Topical corticosteroid therapy reduces symptoms and nasal mucosal
      inflammatory cells in patients with allergic rhinitis. Usually patients are
      advised to start their medication (1 week) before the beginning of the pollen
      season. The effect of pretreatment with a topical corticosteroid on unchallenged
      nasal mucosa is not well documented. OBJECTIVES: The purpose of this study was to
      investigate, in a double-blind, placebo-controlled study, the effect of 6 weeks'
      pretreatment with 200 microg twice daily fluticasone propionate on nasal symptoms
      and inflammatory cell numbers after nasal allergen provocation in patients with
      seasonal allergic rhinitis. METHODS: Nineteen patients with grass pollen-induced
      allergic rhinitis were treated for a 6-week period out of the grass pollen
      season. After completing the treatment period, patients were challenged with
      grass pollen. Nasal mucosal biopsy specimens were taken 5 times in every patient.
      In nasal mucosa changes in numbers of T cells, B cells, mast cells, eosinophils,
      macrophages, and Langerhans' cells were investigated. RESULTS: After 4 weeks of
      treatment but before allergen provocation, significantly fewer epithelial
      Langerhans' cells, macrophages, mast cells, T cells, and eosinophils were found
      in the fluticasone propionate group compared with those found in the placebo
      group. In the lamina propria significantly fewer Langerhans' cells and
      eosinophils were found in the fluticasone propionate group. Cell influx in nasal
      mucosa after allergen provocation was significantly inhibited in the fluticasone
      propionate group compared with that in the placebo group for epithelial
      Langerhans' cells, mast cells, macrophages, and T cells and for lamina propria
      eosinophils, mast cells, Langerhans' cells, macrophages, and T cells.
      CONCLUSIONS: Fluticasone propionate is effective in reducing early- and late
      phase nasal symptoms. Topical corticosteroid treatment reduces inflammatory cells
      in unchallenged nasal mucosa.

PMID- 11295651
TI  - The prevalence of environmental exposure to perceived asthma triggers in children
      with mild-to-moderate asthma: data from the Childhood Asthma Management Program
      (CAMP).
AB  - BACKGROUND: The Childhood Asthma Management Program, a 5-year randomized clinical
      trial of treatments for childhood asthma, has enrolled and characterized a cohort
      of 1041 children with mild-to-moderate asthma. OBJECTIVE: We sought to describe
      self-reported sensitivities and environmental exposures and investigate the
      relationships between self-report of these exposures as asthma triggers and their
      prevalence in the home. METHODS: Self-reports of sensitivities and home exposures
      were obtained by interview with the child or parent. Sensitivities were further
      assessed by using allergy skin testing (prick or puncture) against a core battery
      of allergens. Home exposures were further assessed by using analysis of a home
      dust sample. RESULTS: Environmental exposures were surprisingly common despite
      self-reported sensitivities to environmental factors. Of patients reporting that
      cigarette smoking frequently causes asthma symptoms, 26% reported having at least
      one parent who smokes cigarettes. Thirty-nine percent of patients reporting that
      exposure to animals frequently causes asthma symptoms live with a furry pet in
      their home. We found a smaller proportion of homes with a high level of cat
      allergen (P <.001) among the children who reported that animals frequently or
      always trigger asthma symptoms compared with those who reported that animals
      never or occasionally trigger asthma symptoms, suggesting modification of the
      home environment. No such results were seen for dog exposure. However, clinical
      symptoms did not reduce exposure to parental cigarette smoking (P =.15), house
      dust (P =.31), or damp and musty areas (P =.51). CONCLUSION: These data suggest
      that children with mild-to-moderate asthma are frequently symptomatic and exposed
      to a wide variety of environmental exposures that are perceived to trigger
      symptoms by means of self-report. Although environmental modification of
      asthmatic homes may occur, many children remain exposed to agents that are known
      to trigger their asthma.

PMID- 11295652
TI  - Quantitation of the major fungal allergens, Alt a 1 and Asp f 1, in commercial
      allergenic products.
AB  - BACKGROUND: Alternaria is one of the most important fungi associated with
      allergic disease, whereas Aspergillus fumigatus is involved in a broad spectrum
      of pulmonary diseases. Currently, fungal extracts used for diagnosis in the
      United States are unstandardized, and their allergenic content cannot be compared
      directly. OBJECTIVE: The goal of this study was to compare the variability of
      major allergen levels among US allergenic products derived from fungi:
      specifically, Alt a 1 levels in Alternaria alternata extracts, and Asp f 1 levels
      in A fumigatus extracts. METHODS: A novel 2-site monoclonal antibody ELISA was
      used for measuring Alt a 1 using recombinant Alt a 1 as a standard. Asp f 1 was
      also measured by ELISA. Allergenic products produced by 8 US manufacturers over a
      2-year period were compared, as were multiple lots produced by a single company.
      RESULTS: Alt a 1 levels in Alternaria extracts from 8 companies produced in 1998
      and 1999 ranged from less than 0.01 to 6.09 microg/mL (mean 1.4 +/- 1.6
      microg/mL, n = 15). In general, Alt a 1 levels were consistent within and between
      companies (1.4 +/- 1.1 microg/mL, n = 27), with 21 of 32 (66%) of all extracts
      tested containing 0.7 to 2 microg/mL Alt a 1. Aspergillus extracts showed much
      greater variability in Asp f 1 levels, with extracts from 8 companies containing
      from less than 0.1 to 64 microg/mL Asp f 1 (mean 16.3 +/- 23.9 microg/mL, n =
      15). Overall variability was greater for Aspergillus products within and between
      manufacturers (22 +/- 22 microg/mL Asp f 1, n = 20). CONCLUSIONS: ELISA-based
      assays for specific allergens showed greater consistency among allergenic
      products derived from Alternaria than from Aspergillus. These assays should
      facilitate improved quality control and standardization of fungal allergen
      extracts and lead to the development of more consistent products for clinical
      use.

PMID- 11295653
TI  - TH2 lymphocytes from atopic patients treated with immunotherapy undergo rapid
      apoptosis after culture with specific allergens.
AB  - BACKGROUND: In atopic patients treatment with specific immunotherapy (SIT)
      induced a shift in the balance of T-cell immune response away from a T(H)2-type
      (producing mostly IL-4) in favor of a T(H)1-type T-lymphocyte response (with the
      preferential production of IFN-gamma). However, the mechanisms through which SIT
      acts are less clear. We have recently shown that allergens may induce an
      activation-induced cell death process in lymphocytes from SIT-treated atopic
      patients. OBJECTIVE: This study aimed to determine whether allergen-induced
      apoptosis can occur in a specific subset of cells. METHODS: The study was
      performed in lymphocytes from normal subjects and atopic patients, some of whom
      were treated with SIT. Cells were cultured in the presence of gramineous pollen
      (Lolium perenne) allergenic extracts. Cell phenotype and intracellular cytokine
      expression were measured by means of fluorescent mAbs. Apoptosis was measured by
      using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick end-labeling. Fluorescence was analyzed in a FACScan flow cytometer, and the
      data were evaluated with Consort 30 software. RESULTS: Our results showed that
      allergens induce apoptosis of lymphocytes in SIT-treated atopic patients.
      Apoptosis occurs mainly in T(H)2 lymphocytes with the IL-4+/CD4+ phenotype and
      subsequently increases the percentage of IFN-gamma(+) cells in the culture.
      CONCLUSION: These results suggest that the shift from T(H)2 to T(H)1 induced by
      SIT in atopic patients may be mediated, at least in part, by the induction of an
      activation-induced cell death process in allergen-responder T(H)2 cells.

PMID- 11295654
TI  - Chromosome 14 linkage analysis and mutation study of 2 serpin genes in allergic
      asthmatic families.
AB  - BACKGROUND: Genome and chromosome screens reported DNA markers on chromosome 14
      linked to allergic asthma or intermediate phenotypes in several populations.
      OBJECTIVE: We sought to perform a linkage study on chromosome 14 and a further
      association study on candidate genes mapped in the region found to be linked to
      allergic asthma or intermediate phenotypes. METHODS: The study consisted of a
      sample of 189 families (847 genotyped individuals) from a restricted geographic
      area in northeastern Italy. The subjects were characterized for the following
      phenotypes: allergic asthma, total serum IgE levels, skin prick test responses,
      and bronchial hyperresponsiveness (BHR) to methacholine. Genotyping was done with
      14 DNA markers and 4 polymorphisms in the genes encoding alpha(1)-anti-trypsin
      and alpha(1)-antichymotrypsin (ACT). RESULTS: Multipoint analysis indicated a
      potential linkage of BHR with marker D14S617 (nonparametric linkage z score =
      2.32, P =.01). Transmission disequilibrium of Thr -15Ala in the gene encoding ACT
      was observed with all the phenotypes investigated: allergic asthma, BHR, total
      IgE levels, or skin prick test responses (P =.041,.02,.0053, or.026,
      respectively). CONCLUSION: Chromosome 14 screening and transmission
      disequilibrium testing on the gene encoding ACT suggest that it or a closely
      located gene may be involved in susceptibility to allergic asthma in the Italian
      population.

PMID- 11295655
TI  - IgE in unselected like-sexed monozygotic and dizygotic twins at birth and at 6 to
      9 years of age: high but dissimilar genetic influence on IgE levels.
AB  - BACKGROUND: IgE is a major determinant of allergic disease. Twin analysis of
      serum levels of IgE has been carried out previously in children and adults with
      heritability estimates of 30% to 70% on the basis of ANOVA. OBJECTIVE: This study
      included the analysis of serum IgE in a population of 126 twins, 27 monozygotic
      pairs and 36 dizygotic pairs, studied at birth (cord blood [CB] IgE) and
      consecutively at the age of 6 to 9 years of age (serum IgE). METHODS: IgE was
      determined by means of RIA. ANOVA, correlation analysis, and structural equation
      modeling by maximal likelihood analysis was used for genetic analysis. RESULTS:
      Structural equation modeling by maximal likelihood analysis showed the best
      fitting model to be the AE model (A for additive genetic variance and E for
      environmental variance) both at birth and later in childhood. The estimated
      heritability was 0.92 (95% CI, 0.84-0.95) for CB IgE and 0.78 (95% CI, 0.60-0.87)
      for serum IgE. The correlation between CB IgE and serum IgE was 0.04.
      CONCLUSIONS: The study demonstrated a higher genetic dependency of serum IgE than
      previously recognized. The low correlation between the IgE levels at birth and
      later in childhood suggested that different effector mechanisms may be operating
      at different ages.

PMID- 11295656
TI  - Expression of IFN-gamma-inducible protein; monocyte chemotactic proteins 1, 3,
      and 4; and eotaxin in TH1- and TH2-mediated lung diseases.
AB  - BACKGROUND: Chemokines are involved in the influx of leukocytes into the airways
      in inflammatory lung diseases. The differential cell recruitment characteristic
      of T(H)1 versus T(H)2 immune responses may be associated with differential
      chemokine expression. OBJECTIVE: We investigated the expression of chemokines;
      monocyte chemotactic proteins (MCPs) 1, 3, and 4; eotaxin; and IFN-gamma
      inducible protein 10 (IP-10) in both T(H)1- and T(H)2-mediated lung diseases.
      METHODS: By using immunocytochemistry and in situ hybridization, we examined the
      protein and mRNA expression, respectively, in bronchoalveolar lavage and biopsy
      samples in subjects with asthma, tuberculosis, sarcoidosis, and chronic
      bronchitis. RESULTS: Increased immunoreactivity and mRNA expression of IP-10 and
      of the MCPs was found in the bronchoalveolar lavage fluid and biopsy specimens of
      subjects with asthma and tuberculosis compared with that of control subjects (P
      <.005). IP-10, however, was particularly increased in subjects with sarcoidosis
      (P <.001). Eotaxin, on the other hand, was increased only in patients with asthma
      when compared with control subjects (P <.005). CONCLUSION: This study
      demonstrates that MCP-1, MCP-3, and MCP-4 expression is not specifically
      associated with lung diseases characterized by a particular cytokine profile. In
      contrast, IP-10 is mostly expressed in T(H)1-mediated diseases, and eotaxin
      expression seems to be specifically associated with lung diseases of a T(H)2
      cytokine profile.

PMID- 11295657
TI  - Fusion protein vesicle-associated membrane protein 2 is implicated in IFN-gamma
      induced piecemeal degranulation in human eosinophils from atopic individuals.
AB  - BACKGROUND: Exocytosis is an integral event during IFN-gamma-induced piecemeal
      degranulation in eosinophils. In many tissues soluble N-ethylmaleimide-sensitive
      factor attachment protein receptors (SNAREs), including vesicle-associated
      membrane protein (VAMP), act as specific intracellular receptors to allow granule
      fusion with the membrane during degranulation. However, the mechanisms underlying
      eosinophil piecemeal degranulation induced by IFN-gamma are not well understood.
      OBJECTIVE: We sought to assess whether eosinophils express the vesicular SNARE
      protein VAMP-2 and to determine the involvement of VAMP-2 in IFN-gamma-induced
      piecemeal degranulation. METHODS: Human peripheral blood eosinophils (> or =97%)
      from atopic subjects were subjected to RT-PCR and sequence analysis with specific
      primers for VAMP-2 mRNA. Western blotting and flow cytometric analysis were
      carried out to confirm the identity of VAMP-2 and its susceptibility to cleavage
      by tetanus toxin. Confocal laser scanning microscopy imaging was conducted on
      double-labeled cytospin preparations of eosinophils at 0, 5, 10, 30, and 60
      minutes and 16 hours of IFN-gamma (500 U/mL) stimulation. RESULTS: Eosinophils
      expressed VAMP-2 mRNA (n = 4 donors), which exhibited 100% homology with human
      VAMP-2 cDNA on sequencing. Eosinophils were also found to express tetanus toxin
      sensitive VAMP-2 protein. RANTES and VAMP-2 immunofluorescence were observed to
      colocalize to similar intracellular structures by means of confocal imaging. IFN
      gamma induced a rapid translocation of VAMP-2(+) organelles toward the cell
      membrane in correlation with RANTES. CONCLUSIONS: These findings suggest that
      exocytosis in human eosinophils is regulated by SNAREs, with a specific role
      indicated for VAMP-2 in piecemeal degranulation.

PMID- 11295658
TI  - Airway epithelial cells release eosinophil survival-promoting factors (GM-CSF)
      after stimulation of proteinase-activated receptor 2.
AB  - BACKGROUND: Epithelium is considered an active participant in allergic
      inflammation. Proteinase-activated receptor (PAR) 2 is expressed in a variety of
      cell types, including epithelial cells, and has been implicated in inflammation.
      OBJECTIVE: PAR-2-mediated activation of airway epithelial cells induces the
      release of mediators that could promote eosinophil survival and mediate
      eosinophil recruitment. METHODS: PAR-2-activating peptides were used to activate
      the human airway epithelial cell line A549, as well as primary cultures of small
      airway epithelial cells (SAECs). Human peripheral blood eosinophils were cultured
      in the presence or absence of epithelial cell supernatants. Survival was assessed
      by using an Annexin V apoptosis detection kit. GM-CSF and eotaxin were measured
      by using ELISA. RESULTS: Eosinophils undergo apoptosis in the absence of growth
      factors. Supernatants from PAR-2-activated A549 epithelial cells increased
      eosinophil survival. Supernatants from resting SAECs also increased eosinophil
      survival, but supernatants from PAR-2-activated SAECs showed a greater effect.
      The effect of PAR-2-activated epithelial cell supernatants on eosinophil survival
      was completely inhibited by a neutralizing anti-GM-CSF antibody but not an anti
      IL-5 antibody. Resting A549 cells did not release any detectable GM-CSF, whereas
      PAR-2-activated cells released 35 pg/10(6) cells. Resting SAECs released 754.3
      pg/10(6) cells of GM-CSF, which was further increased to 1360.5 pg/10(6) cells
      after PAR-2-mediated activation. Budesonide inhibited this PAR-2 effect. PAR-2
      activated epithelial cells also released eotaxin. CONCLUSION: PAR-2-mediated
      activation of airway epithelial cells induced release of GM-CSF, which promoted
      eosinophil survival and activation. It also induced release of eotaxin, which
      could mediate eosinophil recruitment to the airways.

PMID- 11295659
TI  - Local expression of epsilon germline gene transcripts and RNA for the epsilon
      heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma.
AB  - BACKGROUND: The demonstration of epsilon germline gene (Cepsilon) transcripts and
      mature mRNA for the epsilon heavy chain gene (Iepsilon) in the nasal mucosa
      suggested that IgE synthesis may occur in allergic rhinitis. OBJECTIVE: In view
      of our previous demonstration of increases in IL-4 mRNA(+) cells in asthmatic
      subjects, we assessed whether local IgE synthesis may also be a feature of
      bronchial asthma. METHODS: Fiberoptic bronchoscopic mucosa biopsy specimens were
      obtained from 9 atopic asthmatic subjects and 10 nonatopic normal (intrinsic)
      control subjects. To control for atopy, we also studied 9 nonatopic asthmatic
      subjects and 10 atopic nonasthmatic control subjects. Tissue was processed for
      immunohistochemistry for B cells (CD20) and in situ hybridization for Iepsilon
      and Cepsilon RNA(+) cells and IL-4 mRNA(+) cells. RESULTS: B-cell numbers in the
      bronchial mucosa were similar for asthmatic subjects compared with control
      subjects, whereas significantly higher numbers of Iepsilon RNA(+) (P =.02 and P
      =.04, respectively), Cepsilon RNA(+) (P =.01 and P =.03, respectively), and IL-4
      mRNA(+) (P =.001 and P =.001, respectively) cells were observed in atopic
      asthmatic subjects and nonatopic asthmatic subjects, respectively, but not in
      atopic control subjects compared with nonatopic control subjects. In asthmatic
      subjects there were significant correlations between Iepsilon RNA(+) cells (r =
      0.54, P =.02) and Cepsilon RNA(+) cells (r = 0.48, P =.05) when compared with the
      number of IL-4 mRNA(+) cells. CONCLUSION: Increases in Iepsilon and Cepsilon
      RNA(+) cells, but not B-cell numbers, in the bronchial mucosa provide evidence
      for local IgE synthesis in both atopic and nonatopic asthma. These changes appear
      to relate to asthma rather than atopy per se and, at least in part, may be under
      the regulation of IL-4.

PMID- 11295660
TI  - Murine model of atopic dermatitis associated with food hypersensitivity.
AB  - BACKGROUND: Atopic dermatitis (AD) is an eczematous skin eruption that generally
      begins in early infancy and affects up to 12% of the population. The cause of
      this disorder is not fully understood, although it is frequently the first sign
      of atopic disease and is characterized by an elevated serum IgE level,
      eosinophilia, and histologic tissue changes characterized early by spongiosis and
      a CD4(+) T(H)2 cellular infiltrate. Hypersensitivity to foods has been implicated
      as one causative factor in up to 40% of children with moderate-to-severe AD.
      OBJECTIVE: The purpose of this study was to establish a murine model of food
      induced AD. METHODS: Female C3H/HeJ mice were sensitized orally to cow's milk or
      peanut with a cholera toxin adjuvant and then subjected to low-grade allergen
      exposure. Histologic examination of skin lesions, allergen-specific serum Ig
      levels, and allergen-induced T-cell proliferation and cytokine production were
      examined. RESULTS: An eczematous eruption developed in approximately one third of
      mice after low-grade exposure to milk or peanut proteins. Peripheral blood
      eosinophilia and elevated serum IgE levels were noted. Histologic examination of
      the lesional skin revealed spongiosis and a cellular infiltrate consisting of
      CD4(+) lymphocytes, eosinophils, and mast cells. IL-5 and IL-13 mRNA expression
      was elevated only in the skin of mice with the eczematous eruption. Treatment of
      the eruption with topical corticosteroids led to decreased pruritus and
      resolution of the cutaneous eruption. CONCLUSION: This eczematous eruption
      resembles AD in human subjects and should provide a useful model for studying
      immunopathogenic mechanisms of food hypersensitivity in AD.

PMID- 11295661
TI  - Prevention of acute urticaria in young children with atopic dermatitis.
AB  - BACKGROUND: There are no published prospective, randomized, double-blind, placebo
      controlled studies of urticaria prevention in children. OBJECTIVE: Our objective
      was to study the effect of long-term treatment with the H(1)-receptor antagonist
      cetirizine in the prevention of urticaria in young children with atopic
      dermatitis. METHODS: In the prospective, double-blind, parallel-group Early
      Treatment of the Atopic Child study, 817 children with atopic dermatitis who were
      12 to 24 months of age at study entry were randomized to receive either
      cetirizine, 0.25 mg/kg, or matching placebo twice daily for 18 months and to be
      followed up for an additional 6 months, during which time the study medication
      code remained unbroken. During both these double-blind phases of the study, for a
      total of 24 months, caregivers prospectively recorded all symptoms and events,
      including hives, in a diary on a weekly basis when the child was well and on a
      daily basis when a symptom or event was observed. The diaries were reviewed and
      validated with the investigators at each regularly scheduled study visit.
      RESULTS: Acute urticaria occurred in 16.2% of the placebo-treated children and in
      5.8% of the children treated with cetirizine (P <.001). The protective effect of
      cetirizine disappeared when treatment was stopped. In the study population as a
      whole, urticaria episodes were most commonly associated with intercurrent
      infection or with food ingestion or direct skin contact. CONCLUSION: Acute
      urticaria is common in toddlers with atopic dermatitis and can be prevented with
      cetirizine in this high-risk population.

PMID- 11295662
TI  - Effectiveness of a medical surveillance program for the prevention of
      occupational asthma caused by platinum salts: a nested case-control study.
AB  - BACKGROUND: Exposure reduction has proven to be effective in the prevention of
      occupational asthma. Few data are available on the effectiveness of secondary
      prevention programs, including medical examinations and removal of workers from
      exposure sources after detecting symptoms or signs indicative of a beginning
      disease. OBJECTIVE: We sought to assess the effectiveness of a medical
      surveillance program in workers with exposure to platinum salts. METHODS: A
      nested case-control study was performed in 14 workers of a catalyst production
      plant whose skin prick test (SPT) responses to platinum salt converted from
      negative to positive during a 5-year prospective cohort study with yearly medical
      examinations and 42 matched control subjects from the plant who did not
      experience SPT response conversion. With the exception of 2 subjects, the workers
      showing SPT response conversion were removed completely from exposure sources and
      followed for up to 42 months. RESULTS: Work-related new symptoms were reported by
      9 of the 14 subjects, and new symptoms without relation to work were reported by
      3 subjects at the time of SPT response conversion. Symptoms were not accompanied
      by a change in FEV(1) or bronchial responsiveness to histamine. Symptoms resolved
      after transferral, but occasional shortness of breath or wheeze persisted in 4
      subjects. SPT reactions decreased or became negative in all workers after
      complete removal but remained unchanged in a craftsman with ongoing occasional
      exposure to contaminated materials. CONCLUSION: Although no randomized
      intervention was performed, this study proves the effectiveness of a medical
      surveillance program for the prevention of occupational asthma caused by platinum
      salts.

PMID- 11295663
TI  - Isolation and molecular characterization of the first genomic clone of a major
      peanut allergen, Ara h 2.
AB  - BACKGROUND: Peanuts have been identified as potent food allergens responsible for
      life-threatening IgE reactions among hypersensitive individuals. With the current
      increase of peanut allergies, there is an urgent need to molecularly characterize
      the genes encoding the target proteins and to understand the nature of their
      regulation. OBJECTIVES: The objectives of this study were to isolate, sequence,
      and characterize at least one full-length genomic clone encoding the major peanut
      allergen Ara h 2. METHODS: A peanut genomic library, constructed in a Lambda Fix
      II vector, was screened with an 80-bp oligonucleotide probe constructed on the
      basis of the 5' end of a published Ara h 2 cDNA partial sequence. One putative
      positive lambda clone was isolated, digested with Bam HI to release its 16-kb
      insert, and confirmed by means of dot blot and Southern hybridization. The
      positive clone was subcloned in pBluescript SK+ vector, sequenced, and
      characterized. RESULTS: Sequence analysis revealed a full-length genomic clone
      with an open reading frame starting with an initiation codon (ATG) at position 1
      and ending with a termination codon (TGA) at position 622. One putative
      polyadenylation signal (AATAAA) is identified at positions 951 in the 3'
      untranslated region, and 6 additional stop codons are located at positions 628,
      769, 901, 946, 967, and 982 downstream from the start codon. In the 5' promoter
      region, a putative TATA box (TATTATTA) is located at position -72 upstream from
      the start codon. The deduced amino acid sequence has 207 residues and includes a
      putative signal peptide of 21 residues. CONCLUSIONS: The results reveal for the
      first time information on the structure of a major peanut allergen, Ara h 2.
      Comparison of the cDNA and genomic sequences revealed the absence of an intron
      but the presence of 2 isoforms of Ara h 2 or different members of the same gene
      family.

PMID- 11295664
TI  - Allergy caused by ingestion of persimmon (Diospyros kaki): detection of specific
      IgE and cross-reactivity to profilin and carbohydrate determinants.
AB  - BACKGROUND: Allergy to persimmon (Diospyros kaki) is very rare and not yet
      confirmed by means of double-blind, placebo-controlled, food-challenge (DBPCFC).
      Thus far, specific IgE to this fruit and cross-reactivity to pollen and other
      foods has not been determined. OBJECTIVE: The objective was to confirm allergy to
      persimmon in 3 patients with an according personal history and to characterize
      allergens and cross-reactivity of specific IgE antibodies to pollen and food
      allergens. One patient reacted with pruritus, penis edema, urticaria, and asthma;
      the second reacted with nausea and vomitus; and the third reacted with
      rhinoconjunctivitis, asthma, and stomachache after ingestion of persimmon.
      METHODS: Patients underwent skin prick testing with routine allergens, latex,
      persimmon, and other foods. Allergy to persimmon was confirmed by means of a
      DBPCFC. Specific serum IgE levels were measured with CAP-FEIA and the enzyme
      allergosorbent test (EAST) method. EAST and immunoblot inhibitions were carried
      out with persimmon; birch, grass, and ragweed pollen; latex; and N-glycans as
      inhibitors. RESULTS: All patients had positive skin test responses, DBPCFC and
      specific IgE assays to persimmon. Blot and EAST inhibition assays revealed IgE to
      cross-reactive profilin in one patient and IgE to cross-reacting carbohydrate
      determinants in all patients. CONCLUSIONS: This is the first report on 3 cases of
      allergy to persimmon verified by means of DBPCFC and detection of specific IgE.
      The sensitization is due to cross-reactive profilin and carbohydrate
      determinants.

PMID- 11295665
TI  - Recombinant allergens Pru av 1 and Pru av 4 and a newly identified lipid transfer
      protein in the in vitro diagnosis of cherry allergy.
AB  - BACKGROUND: In central and northern Europe food allergy to fruits of the Rosaceae
      family is strongly associated with birch pollinosis because of the existence of
      IgE cross-reactive homologous allergens in birch pollen and food. By contrast, in
      the Mediterranean population allergic reactions to these fruits frequently are
      not related to birch pollen allergy and are predominantly elicited by lipid
      transfer proteins (LTPs). OBJECTIVE: We sought to determine the prevalence of IgE
      sensitization to the recombinant cherry allergens Pru av 1 and Pru av 4 in
      comparison with cherry extract within a representative group of patients who were
      allergic to cherries recruited in Germany and to compare the relevance of IgE to
      cherry LTPs in Italian patients. METHODS: Recombinant Pru av 1 and rPru av 4 were
      available from earlier studies. The cDNA of the cherry LTPs was obtained by using
      a PCR-cloning strategy. The protein was expressed in Escherichia coli and
      purified by means of metal chelate affinity chromatography. Sera from 101 German
      patients with birch pollinosis and oral allergy syndrome to cherry and sera from
      7 Italian patients with cherry allergy were investigated by using enzyme
      allergosorbent tests for IgE reactivity with cherry extract, rPru av 1, rPru av
      4, and the recombinant cherry LTP. Inhibition experiments were performed to
      compare the IgE reactivity of natural and recombinant cherry LTPs and to
      investigate potential cross-reactivity with birch pollen allergens. RESULTS: The
      LTP from cherry comprises 91 amino acids and a 26 amino acid signal peptide. The
      mature cherry LTP shows high amino acid sequence identity with allergenic LTPs
      from peach (Pru p 3, 88%), apricot (Pru ar 3, 86%), and maize (Zea m 14, 59%) and
      displays no IgE cross-reactivity with birch pollen. The IgE prevalences in the
      German patients were as follows: LTP, 3 of 101 (3%); rPru av 1, 97 of 101
      (96.0%); rPru av 4, 16 of 101 (16.2%); and cherry extract, 98 of 101 (97%). All 7
      Italian patients had IgE against the cherry LTP. CONCLUSIONS: Recombinant
      allergens are useful tools for a more accurate in vitro IgE-based diagnosis of
      cherry allergy. Taken together, they mimic the allergenic activity of cherry
      extract, having slightly higher biologic activity. Sensitization to the cherry
      LTP is relevant for a minority of patients recruited in Germany, but our data
      indicate that it may be a major allergen in Italy.

PMID- 11295666
TI  - Caesarean section and risk of asthma and allergy in adulthood.
AB  - This study evaluated the relationship of caesarean section to the risk of asthma
      in adulthood. The data were based on a prospective birth cohort born in northern
      Finland in 1966. In 1997, when the members of the cohort were 31 years old,
      information on current doctor-diagnosed asthma and other allergic disorders was
      obtained from 1953 subjects by a self-administered questionnaire and skin prick
      test. Caesarean section had a strong effect on current doctor-diagnosed asthma in
      adulthood with an adjusted odds ratio (OR) of 3.23 (95% CI 1.53, 6.80). However,
      no substantial effects were observed for atopy, hay fever, and atopic eczema.

PMID- 11295667
TI  - L-selectin and intercellular adhesion molecule 1 mediate lymphocyte migration to
      the inflamed airway/lung during an allergic inflammatory response in an animal
      model of asthma.
AB  - T lymphocytes play a critical role in the development of allergic inflammation in
      asthma. Early in the allergic response, T lymphocytes migrate from the
      circulation into the lung to initiate and propagate airway inflammation. The
      adhesion molecules that mediate lymphocyte entry into inflamed lung have not been
      defined. This study directly examined the roles of L-selectin and intercellular
      adhesion molecule 1 (ICAM-1) in lymphocyte migration to the lung during an
      allergic inflammatory response in an animal model of asthma. Short-term (1 hour)
      in vivo migration assays and various combinations of adhesion molecule-deficient
      and wild-type mice were used. Migration of in vivo activated lymphocytes into
      inflamed lung was significantly greater than entry of resting lymphocytes into
      noninflamed lung (24.5% +/- 2.7% vs 9.5% +/- 1.3%, P =.001). Migration of
      activated lymphocytes into inflamed lung was inhibited by 30% in the absence of L
      selectin (17.3% +/- 1.3%, P =.04), 47% in the absence of cell surface ICAM-1
      (13.0% +/- 2.5%, P =.01), and 47% in the absence of endothelial ICAM-1 (13.0% +/-
      2.5%, P =.01). Loss of ICAM-1 on both lymphocytes and lung endothelium inhibited
      lymphocyte migration by 60% (9.8% +/- 1.8%, P =.002). These findings demonstrate
      clear roles for both L-selectin and ICAM-1 in lymphocyte migration to the lung
      during an allergic inflammatory response, with ICAM-1 playing a greater role.

PMID- 11295668
TI  - Overexpression of IL-10 mRNA in gut mucosa of patients with allergic asthma.
AB  - Because an airway-like inflammation has been reported in the gut of asthmatic
      patients, we sought to examine the expression of immunoregulatory cytokines like
      IL-4, IL-10, and IL-13 by gut mucosa. To establish this, we initiated this study
      to examine mRNA expressions of IL-4, IL-10, and IL-13 in duodenal mucosa from
      patients with asthma. Duodenal biopsy specimens were obtained from 20 asthmatic
      patients (10 allergic, 10 nonallergic) and 8 healthy controls. Cytokine mRNA was
      quantified with reverse transcriptase-competitive PCR, and results were expressed
      in proportion to the number of beta-actin mRNA in the same sample. IL-10 and IL-4
      mRNA were detectable in all patients, whereas no IL-13 mRNA was detected. IL-10
      mRNA concentrations were significantly higher in allergic subjects with asthma
      than in control subjects and nonallergic subjects with asthma. No significant
      difference was observed for IL-4. IL-10 mRNA expression was not related to asthma
      severity, FEV(1), blood eosinophilia, or IgE levels. Our results support the
      hypothesis that IL-10 overexpression may counterbalance the effects of
      proinflammatory cytokines and mitigate the inflammatory reaction found in gut
      mucosa of subjects with asthma.

PMID- 11295669
TI  - Association of humoral immunodeficiency, cleidocranial dysplasia, and von
      Willebrand's disease in a family cluster.

PMID- 11295670
TI  - Occupational rhinitis and asthma by Lathyrus sativus flour: characterization of
      allergens.

PMID- 11295671
TI  - Double-blind, placebo-controlled corn challenge resulting in anaphylaxis.

PMID- 11295672
TI  - Comparing conventional and acetone-precipitated dog allergen extract skin
      testing.

PMID- 11295673
TI  - Fluticasone propionate/salmeterol combination.

PMID- 11295676
TI  - Hereditary angioedema type III: an additional French pedigree with autosomal
      dominant transmission.

PMID- 11295678
TI  - Desloratadine: A new, nonsedating, oral antihistamine.
AB  - Desloratadine is a new, selective, H(1)-receptor antagonist that also has anti
      inflammatory activity. In vitro studies have shown that desloratadine inhibits
      the release or generation of multiple inflammatory mediators, including IL-4, IL
      6, IL-8, IL-13, PGD(2), leukotriene C(4), tryptase, histamine, and the TNF-alpha
      induced chemokine RANTES. Desloratadine also inhibits the induction of cell
      adhesion molecules, plateletactivating factor-induced eosinophil chemotaxis, TNF
      alpha-induced eosinophil adhesion, and spontaneous and phorbol myristate acetate
      induced superoxide generation in vitro. In animals desloratadine had no effect on
      the central nervous, cardiovascular, renal, or gastrointestinal systems.
      Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and
      has a half-life of 27 hours. The absorption of desloratadine is not affected by
      food, and the metabolism and elimination are not significantly affected by the
      subject's age, race, or sex. There are no clinically relevant interactions
      between desloratadine and erythromycin, ketoconazole, or grapefruit juice.
      Desloratadine is not a significant substrate of the P-glycoprotein transport
      system. Once daily administration of desloratadine rapidly reduces the nasal and
      nonnasal symptoms of seasonal allergic rhinitis, including congestion. In
      patients with seasonal allergic rhinitis and concomitant asthma, desloratadine
      treatment was also associated with significant reductions in total asthma symptom
      score and use of inhaled beta(2)-agonists. Use of desloratadine in patients with
      chronic idiopathic urticaria was associated with significant reductions in
      pruritus, number of hives, size of the largest hive, and interference with sleep
      and daily activities. Clinical experience in over 2300 patients has shown that
      the adverse event profile of desloratadine is similar to that of placebo;
      desloratadine has no clinically relevant effects on electrocardiographic
      parameters, does not impair wakefulness or psychomotor performance, and does not
      exacerbate the psychomotor impairment associated with alcohol use.

PMID- 11295680
TI  - Strategies to overcome insomnia.

PMID- 11295681
TI  - 2001 and thoughts on technology.

PMID- 11295682
TI  - High-risk pregnancy: preterm labor.

PMID- 11295683
TI  - Strategies for recruitment and retention of health care professionals. Part two:
      the right candidate.

PMID- 11295684
TI  - Medicare reform in 2001--potential impact on home care.

PMID- 11295685
TI  - Home health aide supervision: finding new meaning in existing requirements.

PMID- 11295686
TI  - Telehealth for effective disease state management.

PMID- 11295687
TI  - Conflict of interest.

PMID- 11295688
TI  - Prognostic assessment of uncomplicated first myocardial infarction by exercise
      echocardiography and Tc-99m tetrofosmin gated SPECT.
AB  - BACKGROUND: We evaluate the prognostic value of stress echo and gated single
      photon emission computed tomography (SPECT) after a first uncomplicated acute
      myocardial infarction. METHODS AND RESULTS: We used predischarge maximal
      subjective exercise echocardiography and gated SPECT with technetium 99m
      tetrofosmin to prospectively study 103 patients younger than 70 years with a
      first acute myocardial infarction. During a 12-month follow-up period, 2 patients
      died, 9 had heart failure, and 29 had ischemic complications (4 reinfarction and
      25 angina). Predictive variables for heart failure in multivariate analysis were
      ejection fraction evaluated by echocardiography (odds ratio [OR] 8.5, P =.016) or
      by gated SPECT (OR 10.7, P =.009). Predictive variables for ischemic
      complications in multivariate analysis were less than 5 metabolic equivalents
      (METS) in exercise test (OR 5.2, P =.007) and greater than 15% ischemic extent in
      the polar map (OR 3.6, P =.04) of SPECT. CONCLUSIONS: Exercise echocardiography
      and Tc-99m tetrofosmin gated SPECT were predictive for heart failure, but
      exercise SPECT was the only test with predictive power for ischemic
      complications.

PMID- 11295689
TI  - Dipyridamole myocardial SPECT with low heart rate response indicates cardiac
      autonomic dysfunction in patients with diabetes.
AB  - BACKGROUND: Because dipyridamole is used to assess heart rate (HR) variability,
      we investigated whether a low HR response during dipyridamole single photon
      emission computed tomography (SPECT) in patients with diabetes indicates the
      presence of cardiac autonomic neuropathy (CAN). METHODS AND RESULTS: Subjects
      were 61 non-insulin-dependent diabetes patients without perfusion defects,
      myocardial infarction, or arrhythmia who underwent thallium 201 SPECT imaging.
      The control group comprised 28 subjects without diabetes. HR was measured during
      infusion of dipyridamole at a rate of 0.14 mg/kg/min, and peak-baseline ratios of
      1.20 or less were defined as low. CAN severity was classified by standard
      autonomic function tests as severe (n = 22), mild (n = 19), or none (n = 20). HR
      ratios were significantly attenuated in patients with diabetes compared with
      those in control subjects (1.22 +/- 0.12 vs 1.32 +/- 0.12, P <.001). Among the
      patients with diabetes, HR ratios decreased as CAN severity increased from none
      (1.32 +/- 0.10) to mild (1.23 +/- 0.12, P <.05) to severe (1.13 +/- 0.08, P
      <.005). There was good correlation between HR ratio and R-R interval ratio to
      deep breathing and to Valsalva, and patients with low HR ratios showed an
      attenuated response to both tests (all P <.001). The sensitivity and specificity
      of HR ratios in the detection of CAN were 77% and 74% for severe CAN and 63% and
      90% for mild-to-severe CAN, respectively. CONCLUSIONS: In patients with diabetes
      who have normal dipyridamole SPECT results, an attenuated HR response observed
      during stress indicates a high likelihood of CAN. Further work that assesses
      these results in diabetes patients with coronary artery disease is warranted.

PMID- 11295690
TI  - Prognostic value of dipyridamole SPECT imaging in low-risk patients after
      myocardial infarction.
AB  - BACKGROUND: The prognostic value of perfusion imaging was assessed in low-risk
      patients after myocardial infarction (MI) and compared with clinical and
      angiographic variables. METHODS AND RESULTS: Rest thallium and dipyridamole
      technetium 99m sestamibi single photon emission computed tomography imaging was
      performed in 203 (91%) low-risk patients 3 to 21 days after MI who were enrolled
      in a trial of low-dose warfarin sodium and aspirin. Patients were considered low
      risk with planned nonintervention, on the basis of an uncomplicated course after
      MI, negative submaximal stress electrocardiography, and the absence of
      significant angiographic disease requiring revascularization. During a minimum
      follow-up of 12 months, 69 patients (34%) had clinical events: 1 cardiac death, 7
      MIs, 26 admissions for unstable angina, 18 coronary bypass grafting, and 17
      angioplasty. Univariate analysis identified the extent of significant
      angiographic stenoses (> or =70%) and the extent of scintigraphic defect as
      predictive of future events. On multivariate analysis, the presence of any
      scintigraphic reversibility had the strongest correlation with clinical events,
      with better predictive value than angiographic multivessel stenoses (P =.0006 vs
      P =.003). CONCLUSIONS: In the low-risk population after MI, scintigraphic
      reversibility remains a strong predictor of cardiac events, with greater
      prognostic value than angiographic data. The extent of scintigraphic
      reversibility was directly correlated with clinical events. Therefore
      scintigraphic imaging remains clinically relevant for risk stratification in the
      current low-risk population after MI.

PMID- 11295691
TI  - Preliminary clinical results of photon energy recovery in simultaneous rest Tl
      201/stress Tc-99m sestamibi myocardial SPECT.
AB  - BACKGROUND: The purpose of this study is to report the first clinical results
      obtained with the spectral deconvolution technique photon energy recovery (PER)
      for crosstalk correction in simultaneous rest thallium 201/stress technetium 99m
      sestamibi myocardial perfusion single photon emission computed tomography
      (SPECT). METHODS AND RESULTS: Thirty-four patients with suspected coronary artery
      disease received Tl-201 (111-130 MBq) at rest, followed by single SPECT. Tc-99m
      sestamibi (444-518 MBq) was then injected at stress, followed by dual SPECT.
      Single SPECT data were processed to obtain the following data sets: single raw
      (conventional) Tl-201 and single PER (scatter-corrected) Tl-201. Dual SPECT data
      were processed to obtain the following data sets: dual raw Tl-201, dual PER
      (scatter- and crosstalk-corrected) Tl-201, dual raw Tc-99m, and dual PER (scatter
      corrected) Tc-99m. All data sets were automatically analyzed with Cedars-Sinai
      Quantitative Perfusion SPECT software to derive the relative segmental uptake,
      the summed score, and the summed difference score. The relative segmental uptake,
      the summed score, and the number of patients with significant reversibility
      (summed difference score >2) were 74.84% +/- 12.79%, 3.44 +/- 3.07, and 13,
      respectively, for single raw Tl-201; 80.5% +/- 10.18%, 1.97 +/- 2.25, and 20,
      respectively, for dual raw Tl-201; 69.47% +/- 14.08%, 6.41 +/- 3.68, and 17,
      respectively, for single PER Tl-201; and 69.99% +/- 13.39%, 6.58 +/- 3.63, and
      17, respectively, for dual PER Tl-201. The differences between single and dual
      raw Tl-201 data sets were highly significant, whereas there was no significant
      difference between PER-corrected Tl-201 data sets. CONCLUSIONS: PER is
      quantitatively efficient to correct for crosstalk in patients investigated with
      simultaneous rest Tl-201/stress Tc-99m sestamibi myocardial SPECT.

PMID- 11295692
TI  - Serial assessment of left ventricular function during dobutamine stress by means
      of electrocardiography-gated myocardial SPECT: combination with dual-isotope
      myocardial perfusion SPECT for detection of ischemic heart disease.
AB  - BACKGROUND: Technetium-labeled myocardial perfusion tracers allow simultaneous
      assessment of myocardial perfusion and left ventricular function by
      electrocardiography (ECG)-gated myocardial single photon emission computed
      tomography (SPECT). The purpose of this study was to evaluate left ventricular
      performance during dobutamine stress by means of ECG-gated myocardial perfusion
      SPECT with short-time data collection. METHODS AND RESULTS: After administration
      of Tc-99m sestamibi or tetrofosmin (600-740 MBq), 67 patients with ischemic heart
      disease, including 35 with prior myocardial infarction, were examined by ECG
      gated myocardial perfusion SPECT at rest and during dobutamine stress (at dosages
      of 4, 8, 12, 16, and 20 microg/kg/min, with increments every 8 minutes). The ECG
      gated data collection time was 5 minutes for each dobutamine dosage. After
      acquisition of gated SPECT data at the highest dose, thallium 201 chloride (111
      MBq) was injected, and dual-isotope SPECT was also performed to assess the
      myocardial ischemia. In 32 patients without prior myocardial infarction, the
      sensitivity of individual stenosed-vessel detection with dual-isotope perfusion
      SPECT, with wall motion abnormality obtained from gated SPECT, and with the
      combined method was 55.9%, 52.9%, and 73.5%, respectively, based on coronary
      angiography. ECG-gated SPECT during dobutamine infusion revealed regional wall
      motion abnormalities (worsening or biphasic response) in 19 (57.6%) of 33
      infarcted areas with culprit coronary arterial stenosis. The prevalence of
      reversible perfusion defects on dual-isotope SPECT was higher in segments with
      wall motion abnormalities than in segments with normal wall motion response
      (89.5% vs 42.9%, P <.02). CONCLUSIONS: Myocardial perfusion and left ventricular
      function during dobutamine infusion were analyzed in a single examination by
      means of the combined method. This procedure has the potential to provide
      comprehensive information with which to evaluate patients with ischemic heart
      disease.

PMID- 11295693
TI  - Increased myocardial blood flow during acute exposure to simulated altitudes.
AB  - BACKGROUND: Although only poor data exist on changes in myocardial blood flow
      (MBF) under acute hypoxia, patients with known coronary artery disease are
      advised not to exceed a moderate altitude exposure of about 2000 m above sea
      level. METHODS AND RESULTS: We measured MBF with positron emission tomography
      using O-15--labeled water in 8 healthy human volunteers (aged 26 +/- 3 years
      [mean +/- SD]) at baseline (450 m above sea level, Zurich, Switzerland) and
      during acute hypoxic hypoxemia induced by inhalation of 2 hypoxic gas mixtures
      corresponding to altitudes of 2000 and 4500 m. MBF remained unchanged at 2000 m
      (increase of 10%, not significant) but increased significantly at 4500 m (62%, P
      <.001), exceeding the relative increase in rate pressure product. CONCLUSIONS:
      Our results may explain why exposure to an altitude of 2000 m (corresponding to
      the cabin pressure in most airplanes during flight) is clinically well tolerated,
      even by patients with reduced coronary flow reserve, such as those with coronary
      artery disease. However, at an altitude of 4500 m, MBF increases significantly,
      supporting the recommendation that patients with impaired flow reserve avoid
      exposure to higher altitudes.

PMID- 11295694
TI  - Detection of inflammation in aortic aneurysms with indium 111-oxine--labeled
      leukocyte imaging.
AB  - BACKGROUND: The exact cause of aortic aneurysms is not completely understood.
      Histologically, the atherosclerotic lesions present in an aneurysm contain
      numerous inflammatory cells. This finding represents active atherosclerosis,
      which can cause lesion expansion. In this study we investigated the role of
      scintigraphy in the evaluation of inflammation in aortic aneurysms. METHODS AND
      RESULTS: We performed imaging using indium 111-oxine--labeled leukocytes in 14
      patients with aortic aneurysms (10 thoracic and 4 abdominal) diagnosed by
      computed tomography. Peripheral blood evidence of inflammation was assessed on
      the same day. In 8 patients who subsequently underwent graft replacement of the
      aneurysm, the excised specimen was examined for evidence of inflammatory
      infiltration and correlated with the scintigraphic findings. Scintigraphic
      accumulation of labeled leukocytes was present in 10 of the 14 patients. Although
      all patients had a small increase in the erythrocyte sedimentation rate, there
      was no significant difference in the erythrocyte sedimentation rate between
      patients with positive and negative scintigram results. In 5 of the 8 surgical
      patients with positive scintigram results, the resected specimens demonstrated
      numerous inflammatory cells in the adventitia of the aortic wall and
      atherosclerotic changes in the media. There was no correlation between the
      presence of periaortic inflammatory adhesions at the time of surgery and the
      scintigraphic results. CONCLUSIONS: The accumulation of In-111-oxine--labeled
      leukocytes is a potentially useful scintigraphic marker of inflammatory
      infiltration in aortic aneurysms.

PMID- 11295696
TI  - Reproducibility of Tl-201 and Tc-99m sestamibi gated myocardial perfusion SPECT
      measurement of myocardial function.
AB  - BACKGROUND: We compared the reproducibility of thallium 201 and technetium 99m
      sestamibi (MIBI) gated single photon emission computed tomography (SPECT)
      measurement of myocardial function using the Germano algorithm (J Nucl Med
      1995;36:2138-47). METHODS AND RESULTS: Gated SPECT acquisition was repeated in
      the same position in 30 patients who received Tl-201 and in 26 who received Tc
      99m-MIBI. The quantification of end-diastolic volume (EDV), end-systolic volume
      (ESV), and ejection fraction (EF) on Tl-201 and Tc-99m-MIBI gated SPECT was
      processed independently with Cedars-Sinai QGS (Quantitative Gated SPECT)
      software. The reproducibility of the measurement of ventricular function on Tl
      201 gated SPECT was compared with that of Tc-99m-MIBI gated SPECT. Correlation
      between the 2 measurements for volumes and EF was excellent for the repeated
      gated SPECT studies of Tl-201 (r = 0.928 to 0.986, P <.05) and Tc-99m-MIBI (r =
      0.979 to 0.997, P <.05). However, Bland-Altman analysis revealed the 95% limits
      of agreement (2 SDs) for volumes and EF were narrower by repeated Tc-99m-MIBI
      gated SPECT (EDV 14.1 mL, ESV 9.4 mL, EF 5.5%) than by repeated Tl-201 gated
      SPECT (EDV 24.1 mL, ESV 18.6 mL, EF 10.3%). The root-mean-square values of the
      coefficient of variation for volumes and EF were smaller by repeated Tc-99m-MIBI
      gated SPECT (EDV 2.1 mL, ESV 2.7 mL, EF 2.3%) than by repeated Tl-201 gated SPECT
      (EDV 3.2 mL, ESV 3.5 mL, EF 5.2%). CONCLUSIONS: QGS provides an excellent
      correlation between repeated gated SPECT with Tl-201 and Tc-99m-MIBI. However, Tc
      99m-MIBI provides more reproducible volumes and EF than Tl-201. Tc-99m-MIBI gated
      SPECT is the preferable method for the clinical monitoring of ventricular
      function.

PMID- 11295697
TI  - The extracellular matrix in normal and diseased myocardium.

PMID- 11295695
TI  - Development and validation of a novel technique for murine first-pass
      radionuclide angiography with a fast multiwire camera and tantalum 178.
AB  - BACKGROUND: The use of genetically altered mice as a model system to study
      cardiovascular disease has created a need for accurate and quantitative
      assessment of murine ventricular function. To address this very challenging
      problem, we have developed a technique of murine first-pass radionuclide
      angiography using pinhole imaging and the short-lived isotope tantalum 178 (Ta
      178) with a high-speed multiwire proportional camera (MPC). METHODS AND RESULTS.
      An MPC was fitted with a pinhole lens of 2-mm-diameter aperture positioned 15 cm
      from the camera face. The short-lived isotope Ta-178 (half-life 9.3 minutes) was
      generated from the tungsten 178 (W-178) (half-life 21.7 days)/Ta-178 generator
      and concentrated on site to an injection volume of 15 to 20 microL. Mice were
      imaged in the supine position with the chest wall 3 mm from the camera pinhole
      aperture, and images were acquired at 160 frames per second after a rapid bolus
      injection of Ta-178. In the absence of a true gold standard, the technology was
      validated with measurements in control mice and mice with surgically ligated left
      anterior descending arteries (LADs). In addition, the effects of pharmacologic
      intervention with verapamil and with dobutamine were observed. Finally, peak
      aortic velocity measurements obtained with this technology were compared with
      those obtained with echocardiographic Doppler ultrasonography, the only available
      quantitative comparator. There was a significant decrease in the mean left
      ventricular ejection fraction (LVEF) between normal mice (62% +/- 4.6% [mean +/-
      SEM], n = 12) and mice with experimentally induced myocardial infarction produced
      by surgical LAD ligation (22% +/- 2.0%, n = 41; P <.01). The LVEF decreased from
      51% +/- 5.8% to 37% +/- 3.5% in a group of normal mice receiving verapamil (P
      <.05, n = 8) and increased from 34% +/- 2.2% to 43% +/- 2.3% in a group of LAD
      ligated mice receiving dobutamine (P <.01, n = 48). Peak camera sensitivity
      during first pass was 25,000 cps/mCi injected. Intraobserver and interobserver
      variability of LVEF was studied, yielding r = 0.9639 and 0.9529 and SE of the
      estimate 2.6% and 3.1%, respectively. Reproducibility in serial studies was
      excellent (r = 0.92, SE of the estimate 5.18). CONCLUSIONS: This study
      demonstrates the development and use of a promising new method that uses the
      short-lived radioisotope Ta-178 and MPC for noninvasive quantification of murine
      ventricular function, that produces accurate and highly reproducible results, and
      that can be applied in multiple serial studies.

PMID- 11295698
TI  - The endothelium: dysfunction and beyond.
AB  - Since its anatomic discovery in the 19th century, the endothelium was considered
      to fulfill no other purpose than that of a physical barrier between blood and
      tissue, until Furchgott and colleagues defined endothelium-dependent
      vasoreactivity in the late 1970s. Henceforth, a functional paradigm defined the
      balance between endothelium-derived relaxing factors and endothelium-derived
      contracting factors as the hallmark of endothelial cell integrity. As a
      consequence, any reflection of a deviation from this state was defined as
      endothelial dysfunction, most notably the impairment of vasorelaxation in
      response to pharmacologic stimuli such as acetylcholine or nonpharmacologic
      stimuli such as shear stress and cold pressor. Within the coronary artery tree
      these alterations have been recognized before the development of obstructive
      coronary artery disease, affecting the microcirculation before the epicardial
      conduit vessel. Furthermore, recent clinical trials outlined the prognostic
      significance of these changes, whereby impairment of increase in coronary blood
      flow in response to endothelium-dependent stimuli seemed to be of utmost
      importance. Thus it is intriguing to speculate on the evolving role of myocardial
      perfusion imaging in combination with pharmacologic and nonpharmacologic stimuli
      for the noninvasive assessment of coronary endothelial dysfunction in patients at
      risk for future adverse events. At a minimum, this review aims to put endothelial
      dysfunction into an imaging perspective beyond the scope of the conventional
      approach.

PMID- 11295699
TI  - Cardiac MRI for assessment of myocardial perfusion: current status and future
      perspectives.
AB  - Cardiac magnetic resonance imaging (MRI) has recently been applied successfully
      to the assessment of myocardial perfusion. Cardiac MRI offers potential
      advantages over radioisotopic techniques because it provides superior spatial
      resolution, does not use ionizing radiation, and has no imaging orientation
      constraints. Current MRI perfusion approaches measure the alteration of regional
      myocardial magnetic properties after the intravenous injection of contrast
      agents. Several studies have validated the ability of perfusion MRI to detect the
      presence of significant coronary artery stenoses by detecting decreased signal
      intensity upslope or reduced maximal enhancement in the ischemic territories.
      Perfusion MRI has also been shown to assess accurately the extent of injury after
      a myocardial infarction and the presence of myocardial viability. With the
      introduction of newer contrast media, technologic improvements on MRI hardware
      and software, and the enhancement of quantitative analysis, MRI is likely to
      become a clinical tool for assessment of myocardial perfusion imaging in the near
      future.

PMID- 11295701
TI  - When it is inflamed, it hurts.

PMID- 11295700
TI  - Post-myocardial infarction risk stratification with stress nuclear myocardial
      perfusion imaging versus echocardiography: separate but not equal.

PMID- 11295702
TI  - Overweight and precursors of type 2 diabetes mellitus in children and
      adolescents.

PMID- 11295703
TI  - Yet another target organ of obesity.

PMID- 11295704
TI  - Carvedilol--a new dimension in pediatric heart failure therapy.

PMID- 11295705
TI  - Unrelated cord blood transplantation for correction of genetic
      immunodeficiencies.

PMID- 11295706
TI  - Peptic ulcer disease and current approaches to Helicobacter pylori.

PMID- 11295707
TI  - Adiposity in childhood predicts obesity and insulin resistance in young
      adulthood.
AB  - OBJECTIVE: To determine whether adiposity in children predicts adiposity, insulin
      resistance, and abnormal lipid levels in young adults. STUDY DESIGN: Children (n
      = 31) were recruited into an epidemiologic study at age 13.3 +/- 0.3 years and
      had blood pressure, weight, and height measured. They were reevaluated at age
      21.8 +/- 0.3 years at which time the measurements were repeated, a euglycemic
      insulin clamp was performed, and fasting lipid levels were measured. All values
      are expressed as mean +/- SEM. Data were analyzed by analysis of variance and
      linear regression analysis. RESULTS: Body mass index (BMI) in childhood (22.6 +/-
      0.6) was highly correlated with BMI in young adulthood (26.9 +/- 0.9). Childhood
      BMI was also inversely correlated with young adult glucose utilization (r = -0.5,
      P = .006) and positively correlated with total cholesterol (r = 0.37, P = .05),
      and low-density lipoprotein (LDL) cholesterol (r = 0.48, P = .01). CONCLUSIONS:
      These data confirm that adiposity in childhood is a strong predictor of young
      adult adiposity. In addition, these results demonstrate that cardiovascular risk
      in young adulthood is highly related to the degree of adiposity as early as age
      13.

PMID- 11295709
TI  - Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents.
AB  - OBJECTIVE: To describe the clinical and laboratory features of obesity associated
      proteinuria and focal segmental glomerulosclerosis. STUDY DESIGN: The patients
      were seen over a 12-year period at two large children's hospitals. Renal
      biopsies, performed for the diagnosis of unexplained heavy proteinuria and
      prepared for light, immunofluorescent, and electron microscopy, were read
      independently by two pediatric pathologists. Blood pressure, body mass index,
      serum levels of creatinine, albumin, and cholesterol, and 24-hour urinary protein
      were measured. RESULTS: Seven African American adolescents were identified with
      obesity-associated proteinuria, which was characterized by severe obesity (120 +/
      30 kg), markedly elevated body mass index (46 +/- 11), mild hypertension (134/74
      +/- 10/18 mm Hg), slightly low to normal serum albumin levels (3.6 +/- 0.2 g/dL),
      moderately elevated serum cholesterol levels (196 +/- 60 mg/dL), and elevated 24
      hour protein excretion (3.1 +/- 1.3 g/dL). Calculated creatinine clearance was
      normal in 6 patients and decreased in one. Typical renal histologic features
      included glomerular hypertrophy, focal segmental glomerulosclerosis, increased
      mesangial matrix and cellularity, relative preservation of foot process
      morphology, and absence of evidence of inflammatory or immune-mediated
      pathogenesis. One patient showed a dramatic reduction in proteinuria in response
      to weight reduction. Three patients who were given angiotensin-converting enzyme
      inhibitors had reduced urinary protein losses from 2.9 g to 0.7 g per day. One
      patient developed end-stage renal disease. CONCLUSION: Obese adolescents should
      be monitored for proteinuria, which has distinct clinical and pathologic features
      and may be associated with significant renal sequelae. Such proteinuria may
      respond to weight reduction and/or treatment with angiotensin-converting enzyme
      inhibitors.

PMID- 11295708
TI  - Relation of acanthosis nigricans to hyperinsulinemia and insulin sensitivity in
      overweight African American and white children.
AB  - OBJECTIVES: Acanthosis nigricans (AN) has been proposed as a reliable marker of
      hyperinsulinemia, but its utility for predicting hyperinsulinism has not been
      systematically evaluated in overweight children. We examined the relationship of
      AN to hyperinsulinemia and body adiposity. STUDY DESIGN: One hundred thirty-nine
      children underwent physical examination for AN, body composition studies, an oral
      glucose tolerance test, and a hyperglycemic clamp. RESULTS: Thirty-five children
      (25%) had AN. AN was more prevalent in African Americans (50.1%) than in white
      subjects (8.2%, P < .001). Independent of race, children with AN had greater body
      weight and body fat mass (P < .001); greater basal and glucose-stimulated insulin
      levels during oral glucose tolerance test (P < .001); greater first-phase, second
      phase, and steady-state insulin levels (P < .001); and lower insulin sensitivity
      (P < .001) during the hyperglycemic clamp. After adjusting for body fat mass and
      age, none of these differences remained significant. When categorized by fasting
      insulin, 35% with fasting insulin levels > 20 microU/mL and 50% with fasting
      insulin levels > 15 microU/mL did not have AN. Eighty-eight percent of children
      with fasting insulin levels > or = 15 microU/mL had a body mass index SD score >
      or = 3.0. CONCLUSIONS: AN is not a reliable marker for hyperinsulinemia in
      overweight children. Children with a race-, sex-, and age-specific body mass
      index SD scores > or = 3.0 should be screened for hyperinsulinemia, whether or
      not they have AN.

PMID- 11295710
TI  - C-reactive protein and body mass index in children: findings from the Third
      National Health and Nutrition Examination Survey, 1988-1994.
AB  - OBJECTIVES: To examine the relationship between C-reactive protein (CRP)
      concentration and body mass index (BMI) in children. STUDY DESIGN: With the use
      of data from 5305 children aged 6 to 18 years in the Third National Health and
      Nutrition Examination Survey (1988 to 1994), a cross-sectional health survey, we
      examined whether CRP concentrations were elevated among overweight children.
      RESULTS: Among children whose BMI was below the age- and sex-specific 15th
      percentile, 6.6% of boys and 10.7% of girls had an elevated CRP concentration
      (>2.1 mg/L) compared with 24.2% of boys and 31.9% of girls whose BMI was > or
      =95th percentile. After adjustment was done for age, sex, race or ethnicity,
      poverty income ratio, high-density lipoprotein cholesterol concentration, white
      blood cell count, and history of chronic bronchitis, the adjusted odds of having
      an elevated CRP concentration were 2.20 (95% CI 1.30, 3.75) for children with a
      BMI of 85th to <95th percentile and 4.92 (95% CI 3.39, 7.15) for children with a
      BMI of > or =95th percentile compared with children who had a BMI of 15th to
      <85th percentile. The associations did not differ significantly by age, sex, or
      race or ethnicity. CONCLUSIONS: In a large representative sample of US children,
      CRP concentration was significantly elevated among children with a BMI > or=85th
      percentile, thus confirming previous findings of this association in children and
      extending previous research in adults to children. Excess body weight may be
      associated with a state of chronic low-grade inflammation in children.

PMID- 11295711
TI  - The increasing prevalence of snacking among US children from 1977 to 1996.
AB  - OBJECTIVES: To determine snacking trends and changes in nutrient contribution of
      snacking over time. STUDY DESIGN: Nationally representative data from the 1977-78
      Nationwide Food Consumption Survey (NFCS77), 1989-91 Continuing Survey of Food
      Intake by Individuals (CSFII89), and 1994-96 (CSFII96) were used. The sample
      consisted of 21,236 individuals aged 2 to 18 years. METHODS: For each survey
      year, mean numbers of snacks consumed, mean grams consumed per snack, and mean
      energy intake from snacks were computed, as was contribution of snacking to total
      energy intake and fat intake. Snacking was self-defined, and a snacking occasion
      consisted of all snack foods consumed during a 15-minute period. Differences in
      means between age groups and across survey years were compared. RESULTS: The
      prevalence of snacking increased in all age groups. The average size of snacks
      and energy per snack remained relatively constant; however, the number of
      snacking occasions increased significantly, therefore increasing the average
      daily energy from snacks. Compared with non-snack eating occasions, the nutrient
      contribution of snacks decreased in calcium density and increased in energy
      density and proportion of energy from fat. CONCLUSION: Snacking is extremely
      prevalent in our society. Healthy snack food choices should be emphasized over
      high-energy density convenience snacks for children.

PMID- 11295712
TI  - Gastric bypass surgery in adolescents with morbid obesity.
AB  - OBJECTIVE: The objective was to review retrospectively all patients undergoing
      bariatric surgery at a large university medical center. METHODS: Ten adolescents
      17 years or younger underwent gastric bypass surgery; 7 of 10 adolescents had
      severe obesity-related morbidities. Follow-up >1 year was present in 9 of 10
      adolescents. RESULTS: The average weight before surgery was 148 +/- 37 kg.
      Postoperative recovery was uneventful in all adolescents; 9 of 10 adolescents had
      weight loss in excess of 30 kg (mean weight loss was 53.6 +/- 25.6 kg). Obesity
      related morbidities resolved in all adolescents. Five adolescents had mild iron
      deficiency anemia, and 3 adolescents had transient folate deficiency. Late
      complications requiring operative treatment occurred in 4 of the adolescents.
      CONCLUSION: Gastric bypass surgery was an effective method for weight reduction
      in morbidly obese adolescents. The procedure was well tolerated, with few
      unanticipated side effects. Gastric bypass remains a last resort option for
      severely obese adolescents for whom other dietary and behavioral approaches to
      weight loss have been unsuccessful.

PMID- 11295713
TI  - Carvedilol as therapy in pediatric heart failure: an initial multicenter
      experience.
AB  - OBJECTIVE: The objective was to determine the dosing, efficacy, and side effects
      of the nonselective beta-blocker carvedilol for the management of heart failure
      in children. STUDY DESIGN: Carvedilol use in addition to standard medical therapy
      for pediatric heart failure was reviewed at 6 centers. RESULTS: Children with
      dilated cardiomyopathy (80%) and congenital heart disease (20%), age 3 months to
      19 years (n = 46), were treated with carvedilol. The average initial dose was
      0.08 mg/kg, uptitrated over a mean of 11.3 weeks to an average maintenance dose
      of 0.46 mg/kg. After 3 months on carvedilol, there were improvements in modified
      New York Heart Association class in 67% of patients (P =.0005, chi2 analysis) and
      improvement in mean shortening fraction from 16.2% to 19.0% (P =.005, paired t
      test). Side effects, mainly dizziness, hypotension, and headache, occurred in 54%
      of patients but were well tolerated. Adverse outcomes (death, cardiac
      transplantation, and ventricular-assist device placement) occurred in 30% of
      patients. CONCLUSIONS: Carvedilol as an adjunct to standard therapy for pediatric
      heart failure improves symptoms and left ventricular function. Side effects are
      common but well tolerated. Further prospective study is required to determine the
      effect of carvedilol on survival and to clearly define its role in pediatric
      heart failure therapy.

PMID- 11295714
TI  - The relation between lower limb pooling and blood flow during orthostasis in the
      postural orthostatic tachycardia syndrome of adolescents.
AB  - OBJECTIVES: Postural orthostatic tachycardia syndrome (POTS) is characterized by
      symptoms of lightheadedness, fatigue, and signs of edema, acrocyanosis, and
      exaggerated tachycardia within 10 minutes of upright posture. Our objective was
      to determine how vascular properties contribute to the pathophysiology of POTS in
      adolescents. STUDY DESIGN: We compared 11 patients aged 13 to 18 years with 8
      members of a control group, recording continuous heart rate and blood pressure
      and using strain-gauge plethysmography to measure forearm and calf blood flow and
      to estimate venous pressure while the subjects were supine. Calf blood flow and
      size change were measured during 70 degrees head-up tilt. RESULTS: Resting calf
      venous pressure was higher in the POTS group compared with the control group.
      Resting resistance was decreased in both the forearm (15 +/- 2 vs 30 +/- 4) and
      calf (27 +/- 2 vs 42 +/- 5) in the POTS group. Calf blood flow 60 seconds after
      tilt increased from 1.9 +/- 0.4 mL/100 mL/min to 6.6 +/- 2.3 mL/100 mL/min in the
      POTS group but only by half in the control group. Flow remained elevated in the
      POTS group but decreased to 70% baseline in the control group. Calf volume
      increased twice as much in the POTS group compared with the control group over a
      shorter time (13 vs 30 minutes). CONCLUSIONS: Lower resistance at baseline
      reflects a defect in arterial vasoconstriction in POTS, further exacerbated
      during upright posture.

PMID- 11295715
TI  - Prevalence of 22q11 deletion in fetuses with conotruncal cardiac defects: a 6
      year prospective study.
AB  - OBJECTIVES: Conotruncal malformations (CTMs) are a major feature of 22q11
      microdeletion (22qdel). The prevalence of 22qdel in fetuses harboring these
      defects is unknown. We assessed the prevalence of 22qdel in a population of
      fetuses with conotruncal cardiac defects. STUDY DESIGN: Consecutive fetuses (n =
      261) with a CTM and a normal karyotype were included in the study. All fetuses
      were screened for 22qdel by means of fluorescent in situ hybridization. RESULTS:
      A 22qdel was found in 54 fetuses (20.7%). The proportion of 22qdel for each CTM
      was: tetralogy of Fallot (14/100), pulmonary atresia with ventricular septal
      defect (11/61), tetralogy of Fallot with absent pulmonary valves (6/16),
      interrupted aortic arch (10/22), truncus arteriosus (9/29), and complex
      transpositions of the great arteries (4/33). Additional vascular anomalies were
      present in 75%. Typical abnormal facial appearance at birth or at autopsy was
      observed in 80%, and thymus hypoplasia, in 76%. The pregnancy was terminated in
      41 of 54 cases, including an intrauterine death in one case. The 22qdel was
      inherited in 7.7%. CONCLUSION: Prevalence of the 22qdel is high in fetuses with
      CTMs. The risk of mental retardation associated with the respective risk of
      cardiac surgery for each type of CTM may strongly influence prenatal counseling.

PMID- 11295716
TI  - Variations in intraventricular hemorrhage incidence rates among Canadian neonatal
      intensive care units.
AB  - OBJECTIVES: To examine the variation in intraventricular hemorrhage (IVH)
      incidence among neonatal intensive care units and identify potentially modifiable
      risk factors. STUDY DESIGN: Multiple logistic regression analysis was used to
      examine variations in > or =grade 3 IVH, adjusting for baseline population risk
      factors, admission illness severity, and therapeutic risk factors. Subjects were
      born at <33 weeks' gestational age, admitted within 4 days of life to 1 of 17
      participating Canadian NICU network sites in 1996-97, and had neuroimaging in the
      first 2 weeks of life. RESULTS: Of 5126 subjects <33 weeks' gestational age, 3806
      had neuroimaging reports. Five of 17 sites had significantly (P <.05) different
      crude incidence rates of grade 3-4 IVH (odds ratios [OR] 0.2, 3.2, 2.6, 2.1, 1.9)
      than the hospital with median incidence. With adjustment for baseline population
      risk factors, perinatal risks, and admission illness severity, IVH incidence
      rates remained significantly (P <.05) higher at 3 sites (OR 2.9, 2.3 and 2.1).
      Inclusion of therapy-related variables (treatment of acidosis and vasopressor use
      on the day of admission) in the model eliminated all site differences.
      CONCLUSIONS: IVH incidence rates vary significantly. Patient characteristics
      explain some of the variance. Early treatment of hypotension and acidosis and
      mode of delivery are potentially modifiable factors and warrant further study in
      IVH prevention.

PMID- 11295717
TI  - Reduced osmolarity oral rehydration solution for persistent diarrhea in infants:
      a randomized controlled clinical trial.
AB  - OBJECTIVE: We evaluated and compared the efficacy of the World Health
      Organization (WHO) oral rehydration solution (ORS) and 2 different formulations
      of reduced osmolarity ORSs in infants with persistent diarrhea. STUDY DESIGN:
      Infants with persistent diarrhea (n = 95) were randomized to 1 of the 3 ORSs: WHO
      ORS (control, n = 32), a glucose-based reduced osmolarity ORS (RORS-G, n = 30),
      or a rice-based reduced osmolarity ORS (RORS-R, n = 31) for replacement of
      ongoing stool losses for up to 7 days. Major outcome measures were stool volume
      and frequency, ORS intake, and resolution of diarrhea. RESULTS: Although there
      were variations from one study day to another, the stool volume was approximately
      40% less in the reduced osmolarity ORS groups; consequently, these children
      required less ORS (22% for RORS-G and 27% for RORS-R groups). A higher proportion
      of children in the RORS-R groups also had resolution of diarrhea during the study
      period. No children in any of the treatment groups had hyponatremia. CONCLUSION:
      Reduced osmolarity ORS is clinically more effective than WHO-ORS and may thus be
      advantageous for use in the treatment of children with persistent diarrhea.

PMID- 11295718
TI  - The efficacy of enzyme replacement therapy in patients with chronic neuronopathic
      Gaucher's disease.
AB  - OBJECTIVE: To assess the long-term systemic and neurologic responses to enzyme
      replacement therapy (ERT) with macrophage-targeted glucocerebrosidase in patients
      with type 3 Gaucher's disease. STUDY DESIGN: Patients with type 3 Gaucher's
      disease (n = 21), aged 8 months to 35 years, were enrolled in a prospective
      study. Enzyme dose was adjusted to control systemic manifestations. Clinical and
      laboratory evaluations were performed at baseline and every 6 to 12 months
      thereafter. Patients were followed up for 2 to 8 years. RESULTS: Significant
      improvement in hemoglobin levels, platelet count, and acid phosphatase values
      occurred. Liver and spleen volume markedly decreased, and bone structure
      improved. Nineteen patients had asymptomatic interstitial lung disease
      unresponsive to ERT. Supranuclear gaze palsy remained stable in 19 patients,
      worsened in one patient, and improved in one. Cognitive function remained
      unchanged or improved over time in 13 patients but decreased in 8 patients, 3 of
      whom developed progressive myoclonic encephalopathy accompanied by cranial
      magnetic resonance imaging and electroencephalographic deterioration.
      CONCLUSIONS: At relatively high doses, ERT reverses almost all the systemic
      manifestations in patients with type 3 Gaucher's disease. Most treated patients
      do not deteriorate neurologically. Novel therapeutic strategies are required to
      reverse the pulmonary and neuronopathic aspects of the disease.

PMID- 11295719
TI  - Preventing febrile seizures in children with oral diazepam: can a controlled
      trial truly be "double-blind?".
AB  - OBJECTIVE: To determine in a randomized, double-blind, clinical drug trial in
      children whether parental "blindness" is maintained. STUDY DESIGN: Oral diazepam
      or placebo was given for fevers to 406 children with at least one previous
      febrile seizure. Later, 192 of these families (102 diazepam, 90 placebo) were
      contacted and asked: (1) Did you give your child the study medicine for fevers?
      (2) Do you think you knew your child's treatment group (diazepam or placebo)? (3)
      If you think you knew, why? RESULTS: In the group of children randomly assigned
      to receive diazepam, 69% of their parents guessed correctly. In the group
      assigned to receive placebo, only 19% of parents guessed correctly. Parental
      opinion was influenced mostly by the presence or absence of side effects, and
      treatment efficacy or failure was the next most important factor. CONCLUSION:
      Because in a double-blind clinical trial, many parents can correctly guess that
      their child is receiving active drug, this may influence compliance with the
      protocol. Thus safeguards are needed to reduce parental bias that can invalidate
      the results of double-blind clinical trials.

PMID- 11295720
TI  - Spirometer-triggered high-resolution computed tomography and pulmonary function
      measurements during an acute exacerbation in patients with cystic fibrosis.
AB  - OBJECTIVE: To evaluate a high-resolution computed tomography (HRCT) scoring
      system, clinical parameters, and pulmonary function measurements in patients with
      cystic fibrosis (CF) before and after therapy for a pulmonary exacerbation. STUDY
      DESIGN: Patients (n = 17) were evaluated by spirometer-triggered HRCT imaging,
      clinical parameters, and pulmonary function tests (PFTs) before and after
      treatment. HRCT scans were reviewed by 3 radiologists using a modified Bhalla
      scoring system. RESULTS: Bronchiectasis, bronchial wall thickening, and air
      trapping were identified in all subjects on initial evaluation. The initial total
      HRCT score correlated significantly with the Brasfield score (r = -.91, P <.001)
      and several PFT measures. After treatment, there were improvements in the acute
      change clinical score (ACCS) (P <.001), most pulmonary function measurements, and
      total HRCT score (P <.05). Bronchiectasis, bronchial wall thickening, and air
      trapping did not significantly change. Mucus plugging subcomponent HRCT score,
      slow vital capacity (SVC), forced expiratory volume in 1 second (FEV(1)), and
      forced vital capacity (FVC) (percent predicted) and reversible and total HRCT
      scores were most sensitive to change by effect size analysis. CONCLUSIONS:
      Improvements occurred with treatment in total and reversible HRCT scores, PFTs,
      and ACCS. Total and reversible HRCT scores and percent predicted SVC, FEV1, and
      FVC were the most sensitive to change. The greatest change was seen in the mucus
      plugging subcomponent HRCT score.

PMID- 11295721
TI  - The US Peanut and Tree Nut Allergy Registry: characteristics of reactions in
      schools and day care.
AB  - OBJECTIVE: Severe food-allergic reactions occur in schools, but the features have
      not been described. STUDY DESIGN: Participants in the US Peanut and Tree Nut
      Allergy Registry (PAR) who indicated that their child experienced an allergic
      reaction in school or day care were randomly selected for a telephone interview
      conducted with a structured questionnaire. RESULTS: Of 4586 participants in the
      PAR, 750 (16%) indicated a reaction in school or day care, and 100 subjects or
      parental surrogates described 124 reactions to peanut (115) or tree nuts (9); 64%
      of the reactions occurred in day care or preschool, and the remainder in
      elementary school or higher grades. Reactions were reported from ingestion (60%),
      skin contact/possible ingestion (24%), and inhalation/possible skin contact or
      ingestion (16%). In the majority of reactions caused by inhalation, concomitant
      ingestion/skin contact could not be ruled out. Various foods caused reactions by
      ingestion, but peanut butter craft projects were commonly responsible for the
      skin contact (44%) or inhalation (41%) reactions. For 90% of reactions,
      medications were given (86% antihistamines, 28% epinephrine). Epinephrine was
      given in school by teachers in 4 cases, nurses in 7, and parents or others in the
      remainder. Treatment delays were attributed to delayed recognition of reactions,
      calling parents, not following emergency plans, and an unsuccessful attempt to
      administer epinephrine. CONCLUSIONS: School personnel must be educated to
      recognize and treat food-allergic reactions. Awareness must be increased to avoid
      accidental exposures, including exposure from peanut butter craft projects.

PMID- 11295722
TI  - Weight loss, hypertension, weakness, and limb pain in an 11-year-old boy.

PMID- 11295723
TI  - Unrelated umbilical cord stem cell transplantation for X-linked
      immunodeficiencies.
AB  - Banked unrelated umbilical cord blood matched at 5 of 6 human leukocyte antigen
      loci was used to reconstitute the immune system in 2 brothers with X-linked
      lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M
      syndrome. Pretransplant cytoreduction and posttransplant graft-versus-host
      prophylaxis were given. Hematopoietic engraftment and correction of the genetic
      defects were documented by molecular techniques. Two years after transplantation,
      all 3 patients have normal immune systems. These reports support the wider use of
      banked partially matched cord blood for transplantation in primary
      immunodeficiencies.

PMID- 11295724
TI  - Clofazimine enteropathy in a pediatric bone marrow transplant recipient.
AB  - Clofazimine, previously used in the treatment of leprosy, is now used for
      treatment of Mycobacterium avium complex infection in patients with acquired
      immune deficiency syndrome, dermatologic disorders, and graft-versus-host
      disease. An 11-year-old boy developed a severe enteropathy 2 years after
      initiation of clofazimine treatment for graft-versus-host disease. Clofazimine
      enteropathy caused by crystal deposition can be life-threatening.

PMID- 11295725
TI  - Neonatal diabetes mellitus, enteropathy, thrombocytopenia, and endocrinopathy:
      Further evidence for an X-linked lethal syndrome.
AB  - We describe an unusual family with a fatal genetic syndrome of neonatal diabetes
      mellitus (DM), enteropathy, endocrinopathy, and severe infections with variable
      thrombocytopenia. All affected individuals are male; X-linked inheritance is
      likely. The most common clinical features are neonatal DM, inanition, and
      enteropathy; a variety of other autoimmune phenomena are less frequent. Clinical
      variability within and among families is common, including lack of one or more
      cardinal features. The syndrome is usually fatal, but survival is sometimes
      possible with immunosuppressive therapy. Clinical variability and frequent new
      mutations may contribute to poor recognition and underreporting of similar cases.

PMID- 11295726
TI  - Carnitine transporter defect diagnosed by newborn screening with electrospray
      tandem mass spectrometry.
AB  - The carnitine transporter defect is a potentially fatal but treatable disorder.
      We used electrospray tandem mass spectrometry in the New South Wales (Australia)
      Newborn Screening Programme to measure free carnitine and acylcarnitine species
      in the newborn population. Free carnitine levels in dried blood samples from
      149,000 neonates did not vary markedly between 2 and 8 days of age. Two of 4
      babies subsequently diagnosed clinically with the carnitine transporter defect
      had a free carnitine level in the neonatal blood sample low enough to be detected
      by screening.

PMID- 11295727
TI  - Acute fatty liver of pregnancy associated with short-chain acyl-coenzyme A
      dehydrogenase deficiency.
AB  - There is a correlation between pregnancy complications such as acute fatty liver
      of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD)
      deficiency. We diagnosed another fatty acid beta-oxidation defect, short-chain
      acyl-coenzyme A dehydrogenase deficiency, in an infant when evaluating him
      because his mother had acute fatty liver of pregnancy. Other beta-oxidation
      defects, in addition to LCHAD deficiency, should be considered in children born
      after pregnancies complicated by liver disease.

PMID- 11295728
TI  - Celiac disease presenting with microcephaly.
AB  - A 15-month-old girl with celiac disease presented with microcephaly and
      developmental delay. Head growth resumed during a gluten-free diet. Subsequent
      gluten ingestion resulted in no head growth, areflexia, and increased celiac
      antibodies. All resolved with gluten elimination. Poor head growth may precede
      other clinical manifestations of celiac disease.

PMID- 11295729
TI  - Health-related quality of life in children with celiac disease.
AB  - We have investigated the health-related quality of life of children with celiac
      disease (n = 133) using two generic and one disease-specific questionnaires. In
      general, the children reported an adequate quality of life, similar to that of
      the reference sample (n = 1183).

PMID- 11295730
TI  - Infantile hypertrophic pyloric stenosis and asymptomatic joint hypermobility.
AB  - A significant association with asymptomatic joint hypermobility was observed in
      37 children with a history of infantile hypertrophic pyloric stenosis (P =.0016)
      and their parents (mothers, P <.0001; fathers, P <.05). The subjects with
      articular hypermobility showed an increased frequency of absent mandibular
      frenulum, thereby suggesting the presence of a previously unrecognized, systemic
      abnormality of the extracellular matrix.

PMID- 11295731
TI  - Death as a complication of peripherally inserted central catheters in neonates.
AB  - We report 2 neonatal deaths caused by cardiac tamponade related to peripherally
      inserted central catheters (PICCs). A total of 3 deaths were noted for 390 PICCs
      placed, giving an incidence of 0.76%. To determine the magnitude of neonatal
      death related to PICCs, directors of neonatal intensive care units in the United
      States were surveyed by means of a questionnaire. Myocardial perforation and
      pericardial effusion were reported by 29% and 43%, respectively. Deaths were
      attributed to PICCs by 24% of the respondents. Uniform guidelines need to be
      formulated to avoid this complication.

PMID- 11295732
TI  - Inflammatory linear verrucous epidermal nevus and arthritis: a new association.
AB  - Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare, chronic skin
      condition that begins in early childhood. We present two children with ILVEN and
      arthritis, a previously undescribed association. We discuss the relevance of this
      association and suggest appropriate management for this arthritis.

PMID- 11295733
TI  - "Plastic bronchitis" complicating recovery from congenital heart surgery.

PMID- 11295735
TI  - When a child can't clean her neck.

PMID- 11295734
TI  - Advances in pediatric nephrology: "The serenity to accept the things we cannot
      change" versus the courage to try.

PMID- 11295736
TI  - Lyme disease vaccine as a strategy for prevention.

PMID- 11295739
TI  - Ambulatory blood pressure monitoring and coarctation of the aorta.

PMID- 11295741
TI  - Maternal thyroid deficiency: another consideration in global developmental delay.

PMID- 11295742
TI  - Diabetes mellitus: type 1 or type 2?

PMID- 11295744
TI  - Combination vaccines.

PMID- 11295746
TI  - Partial splenic embolization in lymphangiomatosis.

PMID- 11295748
TI  - The energetics of small internal loops in RNA.
AB  - The energetics of small internal loops are important for prediction of RNA
      secondary and tertiary structure, selection of drug target sites, and
      understanding RNA structure-function relationships. Hydrogen bonding, base
      stacking, electrostatic interactions, backbone distortion, and base-pair size
      compatibility all contribute to the energetics of small internal loops. Thus, the
      sequence dependence of these energetics are idiosyncratic. Current approximations
      for predicting the free energies of internal loops consider size, asymmetry,
      closing base pairs, and the potential to form GA, GG, or UU pairs. The database
      of known three-dimensional structures allows for comparison with the models used
      for predicting stability from sequence.

PMID- 11295749
TI  - Incorporating residual dipolar couplings into the NMR solution structure
      determination of nucleic acids.
AB  - NMR solution structures of nucleic acids are generally less well defined than
      similar-sized proteins. Most NMR structures of nucleic acids are defined only by
      short-range interactions, such as intrabase-pair or sequential nuclear Overhauser
      effects (NOEs), and J-coupling constants, and there are no long-range structural
      data on the tertiary structure. Residual dipolar couplings represent an extremely
      valuable source of distance and angle information for macromolecules but they
      average to zero in isotropic solutions. With the recent advent of general methods
      for partial alignment of macromolecules in solution, residual dipolar couplings
      are rapidly becoming indispensable constraints for solution NMR structural
      studies. These residual dipolar couplings give long-range global structural
      information and thus complement the strictly local structural data obtained from
      standard NOE and torsion angle constraints. Such global structural data are
      especially important in nucleic acids due to the more elongated, less-globular
      structure of many DNAs and RNAs. Here we review recent progress in application of
      residual dipolar couplings to structural studies of nucleic acids. We also
      present results showing how refinement procedures affect the final solution
      structures of nucleic acids.

PMID- 11295750
TI  - Determination of the structure of the RNA complex of a double-stranded RNA
      binding domain from Drosophila Staufen protein.
AB  - We have determined using NMR the structure of the complex between the third
      double-stranded RNA-binding domain (dsRBD3) of Drosophila Staufen protein and a
      RNA stem-loop with optimal binding properties in vitro. This work was designed to
      understand how dsRBD proteins bind RNA and to investigate the role of Staufen
      dsRBDs in the localization of maternal RNAs during early embryonic development.
      The structure determination was challenging, because of weak, nonsequence
      specific binding and residual conformational flexibility at the RNA-protein
      interface. In order to overcome the problems originated by the weak interaction,
      we used both new and more traditional approaches to obtain distance and
      orientation information for the protein and RNA components of the complex. The
      resulting structure allowed the verification of aspects of RNA recognition by
      dsRBDs matching the information obtained by a related crystallographic study. We
      were also able to generate new observations that are likely to be relevant to
      dsRBD-RNA binding and to the physiological role of Staufen protein.

PMID- 11295751
TI  - Ligands recognizing the minor groove of DNA: development and applications.
AB  - Polyamide ligands comprised of pyrrole, imidazole and hydroxypyrrole rings have
      been developed over the past decade which can be used to target many different,
      predetermined DNA sequences through recognition of functional groups in the minor
      groove. The design principles for these ligands are described with a description
      of the characterization of their binding. Variations containing linked
      recognition modules have been described which allow high affinity and specificity
      recognition of DNA sequences of over 15 base pairs. Recent applications of these
      ligands in affecting biological response through competition with proteins for
      DNA binding sites are reviewed.

PMID- 11295752
TI  - Laser ablation of the pulmonary veins by using a fiberoptic balloon catheter:
      implications for treatment of paroxysmal atrial fibrillation.
AB  - BACKGROUND AND OBJECTIVE: Focal sources of paroxysmal atrial fibrillation may be
      treatable by electrical isolation of the pulmonary veins from the left atrium. A
      new fiberoptic balloon catheter was tested as an alternative to radiofrequency
      catheter ablation for creation of circumferential thermal lesions at the
      pulmonary vein orifice. STUDY DESIGN/MATERIALS AND METHODS: In vitro and in vivo
      experiments were conducted in canine hearts to demonstrate efficacy and optimize
      ablation dosimetry. Continuous-wave, 1.06-microm, Nd:YAG laser radiation was
      delivered radially through diffusing optical fiber tips enclosed in a balloon
      catheter. During in vivo studies, the catheter was placed at the pulmonary vein
      orifice through a left atrial appendage sheath under X-ray fluoroscopic guidance
      during an open-chest procedure. Additionally, circumferential lesions in the left
      atrial appendage were correlated with epicardial electrograms demonstrating
      elimination of electrical activity. RESULTS: The pulmonary veins were
      successfully ablated by using laser powers of 30--50 W and irradiation times of
      60--90 seconds. Transmural, continuous, and circumferential lesions were produced
      in the pulmonary veins in a single application without evidence of tissue
      vaporization or endothelial disruption. CONCLUSION: Laser ablation by using a
      fiberoptic balloon catheter may represent a promising alternative to
      radiofrequency catheter ablation for electrical isolation of the pulmonary veins
      from the left atrium during treatment of paroxysmal atrial fibrillation. Further
      development and testing of the fiberoptic catheter is warranted for possible
      clinical studies.

PMID- 11295753
TI  - Attenuation of infarct size in rats and dogs after myocardial infarction by low
      energy laser irradiation.
AB  - BACKGROUND AND OBJECTIVE: The aim of the present study was to investigate the
      possibility that low-energy laser irradiation attenuates infarct size formation
      after induction of chronic myocardial infarction (MI) in small and large
      experimental animals. STUDY DESIGN/MATERIALS AND METHODS: Laser irradiation was
      applied to the infarcted area of rats and dogs at various power densities (2.5 to
      20 mW/cm(2)) after occlusion of the coronary artery. RESULTS: In infarcted laser
      irradiated rats that received laser irradiation immediately and 3 days after MI
      at energy densities of 2.5, 6, and 20 mW/cm(2), there was a 14%, 62%
      (significant; P < 0.05), and 2.8% reduction of infarct size (14 days after MI)
      relative to non--laser-irradiated rats, respectively. In dogs, a 49%
      (significant; P < 0.01) reduction of infarct size was achieved. CONCLUSION: The
      results of the present study indicate that delivery of low-energy laser
      irradiation to infarcted myocardium in rats and dogs has a profound effect on the
      infarct size after MI.

PMID- 11295754
TI  - Intravascular low-power laser irradiation after coronary stenting: long-term
      follow-up.
AB  - BACKGROUND AND OBJECTIVE: A high restenosis rate remains a limiting factor for
      percutaneous transluminal coronary angioplasty and stenting. The objective of
      this study was to evaluate the effect of intravascular red laser therapy (IRLT)
      on restenosis after stenting procedures in de novo lesions. STUDY
      DESIGN/MATERIALS AND METHODS: A total of 68 consecutive patients were treated
      with IRLT in conjunction with coronary stenting procedures. Mean lesion length
      was 16.5 +/- 2.4 mm. Reference vessel diameter (RVD) and pre-minimal lumen
      diameter (MLD) were 2.90 +/- 0.15 mm and 1.12 +/- 0.26 mm, respectively. RESULTS:
      After treatment, MLD was 2.76 +/- 0.32 mm with no procedural complications or in
      hospital adverse events. Angiographic follow-up (n = 61) revealed restenosis in
      nine patients (14.7%) with rate by artery size of > 3 mm (n = 21) 0%; 2.5--3.0 mm
      (n = 28) 14.2%; and < 2.5 mm (n = 12) 41.6%. CONCLUSION: Intravascular red light
      therapy is safe, feasible, and reduces expected restenosis rate after coronary
      stenting.

PMID- 11295755
TI  - Effects of laser irradiation on the spinal cord for the regeneration of crushed
      peripheral nerve in rats.
AB  - BACKGROUND AND OBJECTIVE: The purpose of the present study was to examine the
      recovery of the crushed sciatic nerve of rats after low-power laser irradiation
      applied to the corresponding segments of the spinal cord. STUDY DESIGN/MATERIALS
      AND METHODS: After a crush injury to the sciatic nerve in rats, low-power laser
      irradiation was applied transcutaneously to corresponding segments of the spinal
      cord immediately after closing the wound by using 16 mW, 632 nm He-Ne laser. The
      laser treatment was repeated 30 minutes daily for 21 consecutive days. RESULTS:
      The electrophysiologic activity of the injured nerves (compound muscle action
      potentials--CMAPs) was found to be approximately 90% of the normal precrush value
      and remained so for up to a long period of time. In the control nonirradiated
      group, electrophysiologic activity dropped to 20% of the normal precrush value at
      day 21 and showed the first signs of slow recovery 30 days after surgery. The two
      groups were found to be significantly different during follow-up period (P <
      0.001). CONCLUSION: This study suggests that low-power laser irradiation applied
      directly to the spinal cord can improve recovery of the corresponding insured
      peripheral nerve.

PMID- 11295756
TI  - 830-nm irradiation increases the wound tensile strength in a diabetic murine
      model.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the
      effects of low-power laser irradiation on wound healing in genetic diabetes.
      STUDY DESIGN/MATERIALS AND METHODS: Female C57BL/Ksj/db/db mice received 2 dorsal
      1 cm full-thickness incisions and laser irradiation (830 nm, 79 mW/cm(2), 5.0
      J/cm(2)/wound). Daily low-level laser therapy (LLLT) occurred over 0-4 days, 3-7
      days, or nonirradiated. On sacrifice at 11 or 23 days, wounds were excised, and
      tensile strengths were measured and standardized. RESULTS: Nontreated diabetic
      wound tensile strength was 0.77 +/- 0.22 g/mm(2) and 1.51 +/- 0.13 g/mm(2) at 11
      and 23 days. After LLLT, over 0-4 days tensile strength was 1.15 +/- 0.14 g/mm(2)
      and 2.45 +/- 0.29 g/mm(2) (P = 0.0019). Higher tensile strength at 23 days
      occurred in the 3- to 7-day group (2.72 +/- 0.56 g/mm(2) LLLT vs. 1.51 +/- 0.13
      g/mm(2) nontreated; P < or = 0.01). CONCLUSION: Low-power laser irradiation at
      830 nm significantly enhances cutaneous wound tensile strength in a murine
      diabetic model. Further investigation of the mechanism of LLLT in primary wound
      healing is warranted.

PMID- 11295757
TI  - Cell attachment modulation by radiation from a pulsed light diode (lambda = 820
      nm) and various chemicals.
AB  - BACKGROUND AND OBJECTIVE: Adhesive interactions between cells and extracellular
      matrices play a regulative role in wound repair processes. The objective of this
      investigation is to study the mechanisms of light action on cellular adhesion in
      vitro. The adhesion of HeLa cells to a glass matrix is evaluated after
      irradiation with a pulsed near-infrared (IR) diode and treatment with various
      chemicals. STUDY DESIGN/MATERIALS AND METHODS: A semiconductor diode (820 +/- 10
      nm, 10Hz, 16--120 J/m(2)) is used for irradiation of the cell suspension. In
      parallel experiments, various chemicals (mannitol, melatonin, ethanol, ascorbic
      acid, superoxide dismutase, catalase, rotenone, azide, dinitrophenol (DNP),
      methylene blue, and hydrogen peroxide) are added to the cell suspension before or
      after the irradiation procedure. The cell-glass adhesion is studied by using the
      adhesion assay technique (Lasers Surg. Med. 1996;18:171). RESULTS: It has been
      found that cell-glass adhesion increases in a dose-dependent manner after
      irradiation. The treatment of the cells with antioxidants (free radical
      scavengers), e.g., mannitol, melatonin, ethanol, and ascorbic acid, as well as
      with the ionophore DNP, eliminated the light effect. The respiratory chain
      inhibitors rotenone and azide strongly modified the light effect, depending on
      the dose. The oxidative agents hydrogen peroxide (in a low concentration) and
      methylene blue increased the cell adhesion. Superoxide dismutase did not modify
      the light effect. The effect of the catalase (stimulative or suppressive) was
      dependent on its concentration and treatment sequence. Preirradiation was found
      to decrease (or normalize to the control level) the suppressive effects of some
      chemicals. CONCLUSION: The results obtained are evidence that first, pulsed IR
      radiation with certain parameters modulates the cell-matrix attachment. second,
      free radical and redox processes are involved in the cell-matrix interaction,
      probably at some stage(s) of the photosignal transduction. Third, both types of
      the primary reactions in the respiratory chain, namely, the increase of the
      electron flow and production of the reactive oxygen species, cause a transient
      oxidative stress in the cytoplasm.

PMID- 11295758
TI  - A phantom with tissue-like optical properties in the visible and near infrared
      for use in photomedicine.
AB  - BACKGROUND AND OBJECTIVE: Modeling of light transport in tissue requires
      development of theoretical models and experimental procedures, as well as tissue
      simulating phantoms. Our purpose was to develop a phantom that matches the
      optical characteristics of human skin in the visible and near infrared spectral
      range. STUDY DESIGN/MATERIALS AND METHODS: The phantom consists of a transparent
      silicone rubber in which Al(2)O(3) particles and a cosmetic powder are embedded.
      Layers with thickness as thin as 0.1 mm can be made. The optical properties of
      Al(2)O(3) particles and cosmetic powder, i.e., total attenuation, absorption and
      scattering coefficients, and phase function, have been determined in the visible
      and near infrared spectral range, by using direct and indirect techniques.
      RESULTS: By varying the concentration of scattering and absorbing particles,
      tissue-like layers can be produced with predictable optical properties. In
      particular, mixing at suitable concentration Al(2)O(3) particles and cosmetic
      powder with the silicone rubber, the optical properties of human skin have been
      simulated over a range of wavelengths from 400 to 1,000 nm. The comparison
      between the phantom diffuse reflectance spectrum and that of human skin, averaged
      over a sample of 260 patients, showed a good agreement. CONCLUSION: The proposed
      technique allows to produce a stable and reproducible phantom, with accurately
      predictable optical properties, easy to make and to handle. This phantom is a
      useful tool for numerous applications involving light interaction with biologic
      tissue.

PMID- 11295759
TI  - The 980-nm diode laser as a new stimulant for laser evoked potentials studies.
AB  - BACKGROUND AND OBJECTIVE: Lasers have been used as stimulators for creating pain
      response without stimulating mechanoreceptive fibers. Various laser systems are
      still under investigation on the quest for best laser system. Our objective was
      to test the feasibility of the 980-nm diode laser for LEP (laser evoked
      potentials) studies. STUDY DESIGN/MATERIALS AND METHODS: Laser evoked potentials
      created by using the 980-nm diode laser were recorded by using standard
      electroencephalogram (EEG) techniques. The collimated laser beam was 3 mm in
      diameter. Stimulus duration was set to 200 msec. The power of laser stimulus
      exposed to the dorsum of the right hand of 10 healthy volunteer subjects (5 women
      and 5 men) was varied between 0 and 10 watts to determine the pain threshold. EEG
      signals during the exposure of 1.5 times the threshold value were recorded from
      scalp electrodes placed on areas Fz, Cz, Pz, C3, and C4 according to the
      international 10--20 system. The stimulus presented during the EEG recording was
      described as a bearable pain sensation like a pinprick perception by the
      subjects. After 0.1--30 Hz analog low-pass filtering, 100-msec prestimulus, and
      900-msec poststimulus EEG epochs were recorded at 256 Hz sampling rate and
      evaluated statistically. Thirty stimuli were presented by randomly varying the
      interstimulus duration between 5 and 9 seconds. RESULTS: Latency and amplitude
      values of LEPs were found in accordance with those reported in the literature.
      CONCLUSION: The 980-nm diode laser used is a suitable stimulator for LEP studies.

PMID- 11295760
TI  - Theramal, mechanical, optical, and morphologic changes in bovine nucleus pulposus
      induced by Nd:YAG (lambda = 1.32 microm) laser irradiation.
AB  - BACKGROUND AND OBJECTIVE To examine the biophysical effects of photothermal
      heating on herniated intervertebral discs during laser decompression surgery.
      STUDY DESIGN/MATERIALS AND METHODS: Ex vivo bovine nucleus pulposus specimens
      were irradiated with a Nd: YAG laser (lambda = 1.32 microm, 100 seconds exposure
      time, 9-31 W/cm(2), 4.8 mm spot diameter), whereas changes in tissue thermal,
      mechanical, and optical properties were monitored by using, respectively,
      infrared radiometry, tissue tension measurements, and diffuse reflectance from a
      HeNe probe laser. Morphologic changes and mass reduction were monitored by
      recording shape changes on video and weighing specimens before and after laser
      exposure. RESULTS: At power densities below 20 W/cm(2), evaporation of water and
      specimen volume reduction (shrinking) were consistently observed on video during
      irradiation. In contrast, above 20 W/cm(2), vapor bubbles formed within the
      specimen matrix and subsequently ruptured (releasing heated vapors). When
      radiometric surface temperature approaches approximately 60 to 70 degrees C
      (denaturation threshold for tissue), tissue tension begins to increase, which is
      consistent with observations of specimen length reduction. The onset of this
      change in tissue tension is also reflected in characteristic alterations in
      diffuse reflectance. With cessation of laser irradiation, a sustained increase in
      tissue tension is observed, which is consistent with changes in specimen length
      and volume. Higher laser power results in a faster heating rate and subsequently
      an accelerated tension change. Specimen mass reduction increased with irradiance
      from 19 to 72% of the initial mass for 9--31 W/cm(2), respectively. Irradiated
      specimens did not return to their original shape after immersion in saline (48
      hours) in contrast to air-dried specimens (24 hours), which returned to their
      original shape and size. CONCLUSION: These observations suggest that photothermal
      heating results in irreversible matrix alteration causing shape change and volume
      reduction (observed on video and evidenced by the increase in tissue tension)
      taking place at approximately 65 degrees C. Inasmuch as high laser power results
      in vapor bubble formation and specimen tearing, the heating process must be
      controlled. Diffuse reflectance measurements provide a noncontact, highly
      sensitive means to monitor dynamically changes in tension of nucleus purposus.

PMID- 11295761
TI  - One hundred consecutive treatments with holmium: YAG laser for pulmonary bullae:
      especially in conjunction with gelatin-resorcinol formaldehyde-glutaraldehyde
      glue adhesion.
AB  - BACKGROUND AND OBJECTIVE: We have widely used a Ho:YAG laser to treat bullae
      thoracoscopically. STUDY DESIGN/MATERIALS AND METHODS: Bullae with broad necks
      were treated with a Ho:YAG laser thoracoscopically. Because one patient relapsed
      after application of fibrin glue in the early period, a DEXON (polyglycolic acid)
      mesh patch soaked in fibrin glue was used through a 2-cm opening in the
      subsequent cases. Lastly, gelatin-resorcinol formaldehyde-glutaraldehyde (GRFG)
      glue was applied through a 5-mm opening instead of a DEXON mesh after
      coagulation. RESULTS: In the 38 patients patched with DEXON mesh soaked in fibrin
      glue and 56 patched with GRFG glue after coagulation, none relapsed. CONCLUSION:
      Combined uses of fibrin glue plus DEXON mesh or GRFG glue were effective when
      bullae were treated with the Ho:YAG laser. However, the wound was smaller and
      more cosmetic in the GRFG glue group than in the DEXON mesh plus fibrin glue
      group.

PMID- 11295762
TI  - Multivariate analysis of laryngeal fluorescence spectra recorded in vivo.
AB  - BACKGROUND AND OBJECTIVE: The potential of using various multivariate analysis
      methods for classification of fluorescence spectra acquired in vivo from
      laryngeal tissues in Patients was investigated. STUDY DESIGN/MATERIALS AND
      METHODS: Autofluorescence spectra were measured on 29 normal tissue sites and 25
      laryngeal lesions using 337-nm excitation. Four different multivariate analysis
      schemes were applied. Laryngeal fluorescence spectra from patients who had been
      administered delta-aminolevulinic acid (ALA) were obtained using 405-nm
      excitation and were classified using partial least squares discriminant analysis
      (PLS-DA). RESULTS: For autofluorescence spectra, logistic regression based on
      principal component analysis (PCA) or PLS, or PLS-DA all resulted in
      sensitivities and specificities around 90% for lesion vs. normal. Using ALA and
      405-nm excitation gave a sensitivity of 100% and a specificity of 69%.
      CONCLUSION: Multivariate analysis of fluorescence spectra could allow
      classification of laryngeal lesions in vivo with high sensitivity and
      specificity. PLS performs at least as well as PCA, and PLS-DA performs as well as
      logistic regression techniques on these data.

PMID- 11295763
TI  - Nevus of Ota: a new classification based on the response to laser treatment.
AB  - BACKGROUND AND OBJECTIVE: For 60 years, Tanino's classification has been used to
      classify the extent of nevus of Ota. However, such classification not only fails
      to address variants such as phacomatosis pigmentovascularis but also cannot be
      used to predict the therapeutic outcome. Our objective is to retrospectively
      study our series of laser-treated patients with the aim of re-classifying nevus
      of Ota, so that such important issues can be taken into account. STUDY
      DESIGN/MATERIALS AND METHODS: One hundred nineteen patients that had received Q
      switched laser treatment were recruited into the study. They were recalled for
      interview and examination for evidence of coexisting birthmarks and
      extracutaneous involvement. Two observers assessed the pre- and posttreatment
      clinical photographs for evidence of periorbital under-response (panda's sign),
      defined as the degree of periorbital laser clearing significantly less than
      clearing in the other area. RESULTS: A total of 47.8% of the patients with
      periorbital pigmentation were considered by the observers to have significant
      periorbital under-response (panda's sign). Additionally, 10.1% had other
      birthmarks, and extracutaneous involvement was seen in 31.4% of the patients.
      CONCLUSION: Periorbital under-response is commonly seen in patients with
      periorbital pigmentation. Taking this and other factors into consideration, we
      have proposed a new classification for nevus of Ota that allows for the
      prediction of the clinical outcome of laser treatment.

PMID- 11295764
TI  - Long-term results in the treatment of childhood hemangioma with the flashlamp
      pumped pulsed dye laser: an evaluation of 617 cases.
AB  - BACKGROUND AND OBJECTIVE: Presenting the long-term results of flashlamp-pumped
      pulsed dye laser treatment in 617 hemangiomas to evaluate this treatment
      modality. STUDY DESIGN/MATERIALS AND METHODS: In 548 children, 692 hemangiomas
      were treated with the flashlamp-pumped pulsed dye laser (FPDL) SPTL 1B (Candela
      Corporation, Wayland, MA). The objective of treatment was the inhibition of
      further growth or the induction of regression. The treatment results were
      documented by the treating physician as well as by means of a questionnaire
      delivered to the parents. A total of 617 treatment results could be evaluated.
      RESULTS: After 1--12 treatments (mean, 2.5), we could achieve our treatment
      objective to stop the further growth of the lesion in 96.6% of all hemangiomas.
      In 13.8%, the treatment resulted in a complete remission, a significant
      regression was seen in 14.9%, and 67.9% of the treated lesions showed a
      discontinuation of growth. The percentage of complete remission was especially
      high in small superficial (42.6%) and superficial (19%) hemangiomas. CONCLUSION:
      In the vast majority of the hemangiomas, it was possible to stop further
      progression or induce regression by FPDL treatment. Total regression could be
      achieved in nearly half of the small superficial hemangiomas. Because the
      treatment is fast, effective, and nearly without side effects, we recommend early
      laser treatment especially in superficial and small childhood hemangiomas.

PMID- 11295765
TI  - Toxicity of photodynamic therapy after combined external beam radiotherapy and
      intraluminal brachytherapy for carcinoma of the upper aerodigestive tract.
AB  - BACKGROUND AND OBJECTIVE: To describe the toxicity of photodynamic therapy (PDT)
      in patients with carcinoma of the upper aerodigestive tract who received prior
      treatment with external beam irradiation and intraluminal brachytherapy (IB).
      STUDY DESIGN/MATERIALS AND METHODS: Hospital records of PDT patients were
      reviewed. Three patients who received prior treatment with external beam
      irradiation and IB were identified. Two patients had esophageal carcinoma treated
      with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy)
      followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for
      treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications:
      630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung
      cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at
      1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one
      light application: 630 nm, 150 J/cm, 200 mW/cm). RESULTS: One patient with
      esophagus cancer had formation of a tracheoesophageal fistula, which required
      stent placement. The other esophageal cancer patient developed quadriplegia due
      to an epidural abscess arising from a fistula with the diseased portion of the
      esophagus. The lung cancer patient had massive hemoptysis after the procedure and
      died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary
      artery. CONCLUSION: Patients with upper aerodigestive tract carcinoma who have
      received treatment with both external beam irradiation and IB seem to be at
      higher risk for complications when treated with PDT.

PMID- 11295766
TI  - Photomechanical transdermal delivery of insulin in vivo.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have shown that photomechanical waves
      transiently permeabilize the stratum corneum in vivo. The aim of the present work
      was to investigate the potential of photomechanical waves for systemic drug
      delivery. STUDY DESIGN/MATERIALS AND METHODS: Photomechanical waves were
      generated by ablation of a polystyrene target by a Q-switched ruby laser.
      Systemic insulin delivery in a streptozotocin-diabetic rat model was monitored by
      measuring the blood glucose level. RESULTS: After photomechanical insulin
      delivery, the blood glucose decreased 80 +/- 3% and remained below 200 mg/dl for
      more than 3 hours. Whereas in control experiments (for which insulin was applied
      without photomechanical waves), there was no dramatic change in the blood glucose
      (standard deviation of measurements over 4 hours was 7%). CONCLUSION: The
      application of the photomechanical waves allowed approximately 6-kDa protein
      molecules (insulin) to pass through the stratum corneum and into the systemic
      circulation.

PMID- 11295767
TI  - The subthalamic nucleus: myth and opportunities.

PMID- 11295768
TI  - Caspase-3 activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      treated mice.
AB  - In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson's
      disease (PD), dopaminergic (DA) neurons have been shown to die by apoptosis.
      Moreover, recent postmortem and in vitro results have indicated that apoptotic
      cell death induced by 1-methyl-4-phenylpyridinium (MPP(+)) may be mediated by
      caspase-3. To establish whether caspase-3 activation may indeed play a role in an
      in vivo model of PD, we studied caspase-3 activation in C57Bl/6 mice
      subchronically intoxicated with MPTP. We show that caspase-3 activation peaks
      early, at days 1 and 2 after the end of MPTP intoxication. In contrast, pycnotic
      neurons persist until day 7 postintoxication, indicating that caspase-3
      activation is an early and transient phenomenon in apoptotic death of DA neurons.
      We further demonstrate that loss of tyrosine hydroxylase (TH) immunoreactivity in
      this model is indeed due to cell loss rather than to loss of TH protein
      expression. We conclude that mice subchronically intoxicated with MPTP represent
      a valid PD model to study and manipulate caspase activation in vivo.

PMID- 11295769
TI  - Exacerbated physical fatigue and mental fatigue in Parkinson's disease.
AB  - OBJECTIVE: To characterize fatigue in Parkinson's disease (PD). BACKGROUND:
      Fatigue is a recognized problem in PD. Fatigue can be in the physical realm or in
      the mental realm. Fatigue has not been characterized in PD. METHODS: We
      characterized fatigue in 39 PD patients and 32 age-matched normal controls using
      five questionnaires: A. The Multidimensional Fatigue Inventory (MFI), which
      measures five dimensions of fatigue independently including general fatigue,
      physical fatigue, reduced motivation, reduced activity, and mental fatigue. B.
      The Fatigue Severity Inventory (FSI), which quantifies fatigue in general. C. The
      Profile of Mood States (POMS), which assesses six subjective subscales: tension
      anxiety, depression-dejection, anger-hostility, fatigue-inertia, vigor-activity,
      and confusion-bewilderment. D. Center for Epidemiological Studies-Depression
      Scale (CES-D). E. Visual Analog linear scale of energy (VA-E). RESULTS: PD
      patients scored higher in all of the five dimensions of fatigue in the MFI
      including general fatigue, physical fatigue, reduced motivation, reduced
      activity, and mental fatigue (P < 0.001 except for mental fatigue P = 0.005). The
      severity of physical fatigue did not correlate with that of mental fatigue. PD
      patients scored higher on the FSI, POMS, CES-D, and scored lower on the VA-E. The
      scores in the FSI correlated with general fatigue, physical fatigue, reduced
      activity, and reduced motivation but not with mental fatigue in the MFI.
      Depression correlated with all dimensions of fatigue except physical fatigue in
      the MFI. Disease severity, as measured by Modified Hoehn and Yahr staging, did
      not correlate with any of the measures. CONCLUSIONS: PD patients have increased
      physical fatigue and mental fatigue compared to normals. Physical fatigue and
      mental fatigue are independent symptoms in PD that need to be assessed and
      treated separately.

PMID- 11295770
TI  - Consensus statement on the role of acute dopaminergic challenge in Parkinson's
      disease.
AB  - Available evidence on the practice of acute pharmacological challenge tests in
      parkinsonian patients was reviewed by a committee of experts, which achieved a
      general consensus. The published data deal mainly with the acute administration
      of levodopa and apomorphine in Parkinson's disease. Such challenge may serve
      different purposes, e.g., research, diagnosis, or tailoring of treatment. Unique
      protocols describing the clinical setting and practice parameters are not
      available. The present paper describes the scientific background and supplies
      practical guidelines, whenever possible, to perform and evaluate acute challenge
      tests in parkinsonian syndromes. With the appropriate indication and setting,
      acute challenge tests are useful in diagnosis and therapy of Parkinson's disease
      and related disorders.

PMID- 11295771
TI  - Reliability and validity of a new global dyskinesia rating scale in the MPTP
      lesioned non-human primate.
AB  - Behavioral rating scales for dyskinesia in the non-human primate are frequently
      used to assess the efficacy of new treatments and to provide a clinical
      correlative with neurochemical and neuropathological changes. Although a large
      variety of different scales have been used in non-human primate studies, there is
      no single standardized scale, and none have been evaluated for reliability and
      validity. We are reporting a new global non-human primate dyskinesia rating scale
      (GPDRS) for the squirrel monkey, developed in the context of an independent study
      of dyskinesia. In this report we demonstrate the reliability and validity of this
      scale. The GPDRS is a single-item scale with well-defined points and brevity
      allowing for rapid and easy application for assessing the overall degree of
      dyskinesia. In this study, seven MPTP-lesioned and four non-lesioned (control)
      non-human primates were videotaped following treatment with either levodopa or
      water. To test inter- and intra-rater reliability, three examiners rated the
      videotape independently at two different time points and these assessments were
      compared. The validity of the scale was tested in two phases. First, examiners
      rated the videotape using the GPDRS and the Abnormal Involuntary Movement Scale
      (AIMS), a scale commonly used to rate dyskinesia in the non-human primate, and
      the ratings from each scale were compared. Second, validity was tested in the
      context of an independent dyskinesia study, in which the scale was used to
      distinguish between two treatment groups. The GPDRS was shown to have high inter-
      and intra-rater reliability and to be valid for the assessment of dyskinesia in
      the squirrel monkey. In this report we also demonstrate the inter- and intra
      rater reliability of the AIMS.

PMID- 11295772
TI  - Does stimulation of the GPi control dyskinesia by activating inhibitory axons?
AB  - A 69-year-old woman with Parkinson's disease and levodopa-induced dyskinesias had
      a deep brain stimulation (DBS) electrode inserted into the right globus pallidus
      internus (GPi). During the operation, the GPi was mapped with dual microelectrode
      recordings. Stimulation through one microelectrode in GPi inhibited the firing of
      GPi neurons recorded with another microelectrode 600--1,000 microm distant. The
      inhibition could be obtained with pulse widths of 150 micros and intensities as
      low as 10 microA. Single stimuli inhibited GPi neurons for approximately 50 ms.
      Trains of 300 Hz stimuli inhibited GPi neuron firing almost completely.
      Postoperatively, stimulation through macroelectrode contacts located in the
      posterior ventral pallidum controlled the patient's dyskinesias. The effect could
      be obtained with pulse widths of 50 micros and frequencies as low as 70--80 Hz.
      We postulate stimulation of the ventral pallidum controls dyskinesias by
      activating large axons which inhibit GPi neurons.

PMID- 11295773
TI  - Cardiovascular reflex testing contributes to clinical evaluation and differential
      diagnosis of Parkinsonian syndromes.
AB  - The differentiation between Parkinson's disease (PD), progressive supranuclear
      palsy (PSP), and multiple system atrophy (MSA) may be difficult but is important
      for prognostic and therapeutic purposes. Varying degrees of autonomic failure
      have been described in PD and MSA, whereas its involvement in PSP remains
      controversial. The aim of this study was to investigate autonomic function in
      patients fulfilling strict clinical diagnostic criteria for the disorders above,
      to evaluate the diagnostic capacity of laboratory autonomic tests. The study
      group was consecutively recruited among patients referred to a movement disorder
      unit. Thirty-four patients with PD, 15 patients with PSP, and 47 patients with
      MSA were compared with 18 healthy age-matched controls. Autonomic tests included
      analysis of heart rate variability (HRV) in temporal domain, at rest and during
      forced respiration, as well as blood pressure (BP) changes during 75 degrees head
      up tilt. HRV did not differ between groups during quiet breathing but was
      significantly reduced during forced respiration in MSA (P < 0.01), while PD and
      PSP groups did not differ from controls. Hypotensive responses during orthostatic
      provocation were seen in PD (P < 0.01) and MSA (P < 0.001), whereas BP remained
      stable in most PSP patients, not differing from the healthy control group. On an
      individual basis, decreased HRV and severe hypotensive responses were seen in MSA
      patients regardless of age and disease duration, whereas PD patients showed this
      combination only at high age and long duration. In PSP, only a few cases with
      decreased HRV and limited hypotensive responses were found. We conclude that
      cardiovascular reflex tests can supplement the clinical differentiation of
      Parkinsonian syndromes.

PMID- 11295774
TI  - Nocturnal body core temperature falls in Parkinson's disease but not in Multiple
      System Atrophy.
AB  - OBJECTIVE: To evaluate whether the circadian rhythm of body core temperature (CRT
      degrees ) can differentiate Multiple-System Atrophy (MSA) from Idiopathic
      Parkinson's disease (IPD). METHODS: We evaluated 14 patients with probable MSA,
      seven with IPD, and eight controls. After a preliminary evaluation of
      cardiovascular autonomic function, rectal temperature and sleep-wake cycle were
      monitored continuously for 48 hours in a temperature-controlled room, at constant
      bed rest with controlled food intake and fixed light-dark schedule. RESULTS: MSA
      patients showed cardiovascular autonomic sympathetic and parasympathetic failure.
      IPD had normal cardiovascular autonomic function. A 24-hour rhythm of body core
      temperature (BcT degrees ) was present in all subjects. IPD had CRT degrees
      comparable to controls. In MSA the mesor was higher and mean BcT degrees of each
      hour was significantly higher from 11 p.m. to 7 a.m. The analysis of mean BcT
      degrees during the different sleep phases showed significantly higher values
      during both NREM (1--2, 3--4) and REM sleep stages in MSA. CONCLUSIONS: The
      physiological nocturnal fall of BcT degrees is blunted in MSA patients mainly
      because BcT degrees did not decrease during sleep. This CRT degrees pattern is
      not justified by differences in sleep structure and may reflect an impairment of
      central sympathetic nervous system function.

PMID- 11295775
TI  - Erythropoietin deficiency and anaemia in multiple system atrophy.
AB  - Serum erythropoietin (EPO) levels are partially controlled by the sympathetic
      outflow to the kidney. We have studied whether patients with multiple system
      atrophy (MSA), known to be associated with dysautonomia, are EPO-deficient.
      Eighteen MSA patients were studied along with 32 idiopathic Parkinson's disease
      (PD) patients, 23 controls with iron-deficiency anaemia, and 18 healthy
      individuals. Serum creatinine was normal in all groups. Mean haemoglobin (Hb)
      concentration in MSA patients was 13.7 +/- 1.7 g/dL. Four MSA patients had
      unexplained anaemia (minimum Hb: 10.5 g/dL) and abnormal autonomic function tests
      including significant postural hypotension, whereas none of the PD patients was
      anaemic. Serum EPO levels were suppressed in relation to anaemia in MSA patients
      compared to elevated EPO levels in iron-deficiency anaemia patients (difference
      of regression lines P < 0.001), indicating EPO deficiency in the anaemic MSA
      patients. Serum EPO levels in PD patients were within normal range. A subset of
      MSA patients has anaemia and postural hypotension, which may be associated with
      EPO deficiency. This may have therapeutic implications.

PMID- 11295776
TI  - Impairment of eyeblink classical conditioning in progressive supranuclear palsy.
AB  - In a previous study we showed that learning in eyeblink classical conditioning
      (EBCC) is normal in Parkinson's disease (PD) and that the serial reaction time
      task (SRTT) is only marginally impaired. Since pathological lesions are more
      widespread in the atypical parkinsonian disorder of progressive supranuclear
      palsy (PSP) than in PD, we hypothesized that PSP patients may show more profound
      deficits in the EBCC and SRTT learning tasks. We therefore investigated EBCC with
      a delay and two trace paradigms, an SRTT and the California Verbal Learning Test
      (CVLT) in eight patients with PSP and an age-matched control group. In all EBCC
      paradigms, we found a significant difference between groups with no significant
      learning in PSP patients. In the SRTT, implicit learning may have been impaired,
      but verbal and manual sequence recall were only marginally impaired. Verbal
      memory was significantly worse in PSP patients than in the control group. Our
      study shows a dissociated pattern of learning abilities in PSP, where the EBCC as
      a measure of implicit learning is impaired, the explicit sequence detection in
      the SRTT is relatively preserved, and the verbal memory impaired. We hypothesize
      that the PSP patients' deficits in EBCC learning may be due to lesions of deep
      cerebellar nuclei. There may be a clinical role for EBCC in distinguishing PD and
      PSP patients.

PMID- 11295777
TI  - Dystonia in corticobasal degeneration.
AB  - OBJECTIVE: To characterize the clinical features, particularly dystonia, in
      patients with clinically diagnosed or pathologically proven corticobasal
      degeneration (CBD). BACKGROUND: Although dystonia has been reported in many
      neurodegenerative disorders, it has not been studied in CBD. Dystonia, often
      accompanied by painful rigidity and fixed contractures, is one of the most
      disabling features of CBD. METHODS: The medical records, imaging studies, and
      videotapes of 66 patients who satisfied the clinical criteria of CBD, evaluated
      between 1988 and 1998, were reviewed. The occurrence, nature, and distribution of
      dystonic features were analyzed and correlated with other features of CBD.
      RESULTS: Of the 66 patients with CBD, 39 (59.0%) had dystonia. The mean age at
      onset of initial symptoms was 63.9 years (range 44--75). In 20 (51.0%) patients,
      dystonic symptoms began in one arm, while 13 (33.0%) patients had initial leg
      involvement. At least one arm was affected in 36 (92.0%) dystonic patients.
      Although 11 (28.0%) patients had leg dystonia, the leg was the predominant site
      of involvement in only 1 patient. Only 12 (31.0%) patients had dystonia involving
      the head, neck, or trunk in the course of the disease. The diagnosis of CBD was
      confirmed in all 4 patients who had autopsies. CONCLUSION: In this large series
      of CBD patients we found that asymmetric limb dystonia, particularly affecting
      one arm, is a common manifestation of CBD; dystonia may be the initial
      manifestation of this neurodegenerative disorder. Axial or leg dystonia, without
      significant involvement of an arm, is rare. There is no effective treatment for
      this relentless disorder, except for temporary relief of dystonia and pain, with
      local botulinum toxin injections.

PMID- 11295778
TI  - Bilateral striopallidodentate calcinosis: clinical characteristics of patients
      seen in a registry.
AB  - Clinical features in bilateral striopallidodentate calcinosis (BSPDC), popularly
      referred to as Fahr's disease (five autosomal dominant families and eight
      sporadic cases, n = 38), recruited through a registry, are reported. Applying
      uniform criteria, cases reported in the literature (n = 61) were combined for
      detailed analysis. The mean (+/- S.D.) age of Registry patients was 43 +/- 21 and
      that of literature was 38 +/- 17. In combined data set (n = 99), 67 were
      symptomatic and 32 were asymptomatic. Of the symptomatic, the incidence among men
      was higher compared with women (45:22). Movement disorders accounted for 55% of
      the total symptomatic patients. Of the movement disorders, parkinsonism accounted
      for 57%, chorea 19%, tremor 8%, dystonia 8%, athetosis 5%, and orofacial
      dyskinesia 3%. Overlap of signs referable to different areas of central nervous
      system (CNS) was common. Other neurologic manifestations included: cognitive
      impairment, cerebellar signs, speech disorder, pyramidal signs, psychiatric
      features, gait disorders, sensory changes, and pain. We measured the total volume
      of calcification using an Electronic Planimeter and Coordinate Digitizer. Results
      suggest a significantly greater amount of calcification in symptomatic patients
      compared to asymptomatic patients. This study suggests that movement disorders
      are the most common manifestations of BSPDC, and among movement disorders,
      parkinsonism outnumber others.

PMID- 11295779
TI  - Validation for tremor quantification of an electromagnetic tracking device.
AB  - An electromagnetic tracking system was used to record arm motion in subjects with
      Parkinson's disease (n = 23), essential tremor (n = 28) or without neurological
      disease (n = 4). Tremor magnitude was calculated by averaging the three
      dimensional displacement of individual tremor bursts. Tremor magnitude calculated
      in this manner was quite closely correlated with a clinician's estimate (r = 0.88
      and 0.86 for Parkinsonian and essential tremors, respectively) and was
      reproducible (r = 0.93 for repeated recordings). The accuracy of the device and
      algorithm was confirmed by mechanically generating oscillations of known
      magnitudes and frequencies. This device is adaptable for quantifying different
      types of tremors and its accuracy is easy to verify. Because position rather than
      acceleration is tracked, tremor amplitude can be stated in readily comprehensible
      units.

PMID- 11295781
TI  - Perceived stigma in Spasmodic Torticollis.
AB  - Little is known about the "stigmatizing" effects of Spasmodic Torticollis--a
      condition that produces physical disfigurement. This is important in
      understanding the social dimensions of this disorder. This study examined the
      presence, the dimensions, and the degree of perceived stigma in patients with
      Spasmodic Torticollis. The study was completed in two stages. In the first stage,
      ten patients were interviewed to identify the effects of their condition on their
      social interactions. In the second stage, a self-rating measure of stigma and
      questions about the impact of the condition on the patients' lives were devised.
      Perceived stigma was defined as avoidance of others, avoidance by others, self
      consciousness, feeling unattractive, feeling apologetic, and feeling different
      from others. The questionnaires were sent to one hundred patients. The majority
      of the patients perceived "some" or "severe" stigma. Stigma was found to affect
      the patients' social, private, and working lives. It is suggested that stigma in
      Spasmodic Torticollis needs to be considered as a parameter relevant to the
      clinical management of these patients.

PMID- 11295780
TI  - Orthostatic tremor arises from an oscillator in the posterior fossa.
AB  - We tested the hypotheses that orthostatic tremor is generated by a central
      oscillator and that the tremor is expressed through spinal Ib interneurons. Six
      patients with orthostatic tremor were examined. The tremor was reset by
      electrical stimulation over the posterior fossa at intensities that were below
      the threshold for a motor evoked potential (MEP) but was not reset by
      transcranial magnetic stimulation over the motor cortex that did produce an MEP.
      It is argued that the oscillator involves the cerebellum or brainstem. The
      inhibition of voluntary EMG produced by stimulation over tendons, which has been
      attributed to effects from Golgi tendon organs (GTO), was not modulated in
      synchrony with the tremor. We were unable to demonstrate, therefore, that the
      tremor is expressed through GTO interneurons with this method.

PMID- 11295783
TI  - CYP2D6 polymorphism in Parkinson's disease: the Rotterdam Study.
AB  - The CYP2D6 polymorphism has been studied extensively in association with
      Parkinson's disease (PD), with no consistent results. Several explanations, such
      as differences in study design or bias in the selection of the control
      population, have been offered for these inconsistent results. We designed a case
      control study nested within a prospective population-based cohort study in which
      cases and controls were sampled from the same source population. To assess the
      significance of the CYP2D6 gene in PD, we investigated two mutant alleles,
      CYP2D6*3 and CYP2D6*4, associated with poor metabolism and the wild type allele
      in 80 patients with PD and 156 matched controls, frequency matched on age and
      gender. No differences between cases and controls were found for the poor
      metabolizer genotype. However, we found that in contrast to earlier reports, the
      CYP2D6*4 mutant allele frequency was lower in cases as compared to controls,
      albeit not statistically significant. Our result supports the hypothesis that the
      CYP2D6 gene is not a major gene responsible for PD.

PMID- 11295782
TI  - To test or not? The value of diagnostic tests in cervical dystonia.
AB  - It has long been suspected that idiopathic cervical dystonia is result of a
      dysfunction of the brain, but the cause of the disease has been elusive. The
      purpose of this study was to determine the diagnostical value of different
      radiological and laboratory tests in cases of cervical dystonia. Cerebral
      computer tomography and/or cerebral magnetic imaging were carried out in all of
      the 149 patients who were included in this study. A total of 25 scans revealed
      some minor findings that did not alter patients' management. Of the 128 cervical
      plain x-ray examinations, 63.1% showed degenerative changes. Cerebrospinal fluid
      (CSF) was examined in 125 patients, and was normal in 103. Some degree of
      pathology was found in the remaining 22 CSF samples. All patients under the age
      of 50 years were tested for serum ceruloplasmin and no decreased level was found.
      Seven patients had elevated ANA titre; four of them also developed Botulinum
      toxin antibodies. We can conclude that the detection rate of pathologic findings
      in patients with idiopathic cervical dystonia is similar to what we can expect in
      the general population, provided the neurological findings are normal apart from
      the involuntary movements. In the adult form of typical cervical dystonia we do
      not recommend any standard laboratory or imaging tests if the neurological
      examination is normal aside from the abnormal head movements.

PMID- 11295784
TI  - Bereitschaftspotential in depressed and non-depressed patients with Parkinson's
      disease.
AB  - Impaired initiation and slowed execution of movements are two of the principal
      characteristics of Parkinson's disease (PD). A similar pattern of movement
      impairments (psychomotor retardation) can be seen frequently in patients with
      idiopathic depression. In addition, affective disorders have been frequently
      reported in patients with different basal ganglia disorders. The aim of this
      study was to determine whether there are some particularities in the cerebral
      electrical activity during the preparation and execution of voluntary internally
      paced movements (i.e., Bereitschaftspotential, BP) in depressed PD patients,
      which can distinguish them from non-depressed PD patients, as well as from
      healthy controls. The BPs were recorded in 16 patients with idiopathic PD, eight
      of whom were depressed (PD-D), and eight of whom were not (PD-ND). Additional
      recordings were taken from a group of eight age- and sex-matched healthy
      subjects. Depression was classified using the Research Diagnostic Criteria and
      the two PD groups were matched for age, disease severity, and disease duration.
      The amplitudes and slopes of the BPs from PD patients were generally smaller than
      in controls, but there was no specific pattern of BP changes that distinguished
      depressed from non-depressed PD patients. In addition, there was no particular
      association between measures of depression severity and BP parameters. The data
      suggest that presence of depression in PD might not have any additional
      deteriorating influence on already impaired preparation for self-paced
      spontaneous movements.

PMID- 11295785
TI  - Long-duration effect and the postsynaptic compartment: study using a dopamine
      agonist with a short half-life.
AB  - A possible reason why levodopa induces a sustained, stable motor benefit during
      the first months to years of therapy may be its long duration of action. This
      long-duration effect may be due either to a presynaptic storage mechanism or to
      postsynaptic pharmacodynamic changes. We previously reported that the dopamine
      agonist ropinirole induced a long-duration response (LDR) in levodopa-naive
      patients with Parkinson's disease. In this study, we investigated motor responses
      to the short half-life dopamine agonist lisuride in a group of levodopa naive
      parkinsonian patients. Once lisuride reached its maximum effect, it was
      substituted, in randomized order, with placebo. Neither investigators nor
      patients knew when the active drug was switched to placebo. When patients were
      switched from lisuride to placebo, their Unified Parkinson's Disease Rating Scale
      (UPDRS) motor scores and tapping test and screw scores declined to baseline
      values within a mean 9.0 +/- 1.9 days. The results confirmed that, like
      ropinirole and levodopa, the short-acting dopamine agonist lisuride induces a
      long-duration response, probably due to postsynaptic changes.

PMID- 11295786
TI  - Do unilateral ablative lesions of the subthalamic nucleu in parkinsonian patients
      lead to hemiballism?
AB  - We report the safety results in nine patients with advanced idiopathic
      Parkinson's disease (PD) who underwent ablative surgery of unilateral subthalamic
      nucleus (STN). In eight patients, surgical objectives were attained without
      induction of abnormal involuntary movements or other adverse effects. One patient
      developed transient hemiballistic movements which improved within 2 weeks after
      surgery. Assessment at 2 weeks to 20 months postoperatively revealed no long-term
      adverse effects. We conclude that hemiballism following unilateral ablation of
      STN in patients with PD is a rare phenomenon, and unilateral ablative lesions of
      STN can be performed safely.

PMID- 11295787
TI  - Parkinson's disease with late Pick's dementia.
AB  - We report a case in which typical clinical features of idiopathic Parkinson's
      disease existed for seven years prior to the development of significant
      behavioral and cognitive changes and severe dementia. The patient presented with
      right-sided resting tremor, bradykinesia, and rigidity, which were highly
      responsive to levodopa. Serial neuropsychological evaluation revealed no evidence
      of dementia until late in the disease. The patient deteriorated rapidly eight
      years into the disease, requiring full care. She died 16 years after symptom
      onset and post-mortem neuropathological analysis revealed Lewy body Parkinson's
      disease and Pick's disease. To our knowledge, this is the first non-familial case
      with this combination of clinical history and pathologically confirmed disease to
      be reported in the literature. The absence of a family history of any
      neurological disease sets this case apart from the recently described genetic
      cases of frontotemporal dementia with Parkinsonism linked to chromosome 17. In
      addition, the relatively late onset of dementia in frontotemporal dementia is
      atypical. While there is considerable debate regarding the cause of dementia in
      idiopathic Parkinson's disease, our case illustrates that Pick's disease is one
      such cause.

PMID- 11295789
TI  - Impact of Huntington's disease on quality of life.
AB  - The purpose of this study was to systematically assess the impact of Huntington's
      disease (HD) on patients' health-related quality of life (QOL). Seventy-seven
      patients with a clinically confirmed diagnosis of HD were interviewed by means of
      the Sickness Impact Profile (SIP). Additional data were gathered on patients'
      motor performance by means of the motor section of the Unified Huntington Disease
      Rating Scale (UHDRS), and cognitive performance by means of the Mini-Mental State
      (MMS). Patients had high scores on the SIP subscales, indicating moderate to
      severe functional impairment. Total Motor Score (TMS), MMS scores, and the
      duration of HD were significantly correlated with patients' scores on the SIP,
      and predicted a significant amount of variance of the Physical Dimension of the
      SIP, but not of the Psychosocial Dimension. We conclude that HD has a great
      impact on patients' physical and psychosocial well-being, the latter being more
      severely affected. Implications for further research and clinical practice are
      discussed.

PMID- 11295788
TI  - Family history information on essential tremor: potential biases related to the
      source of the cases.
AB  - The proportion of essential tremor (ET) cases that can be attributed to genetic
      factors is unknown; estimates range from 17--100%. One possible reason for this
      variability is that clinic and community cases may differ with regard to family
      history of ET. This is because clinic patients are self-selected and represent as
      few as 0.5% of all ET cases. Our goal was to determine whether ET cases
      ascertained from a clinic differed from those ascertained from a community in
      terms of the family history information that they provided. Subjects (57 clinic,
      64 community) underwent a family history interview. Clinic cases were 4.73 times
      more likely to report an affected relative than were community cases. We conclude
      that there was a substantial difference between our clinic and community ET cases
      in terms of the information they provided regarding their family history.
      Selection and reporting biases could have accounted for this difference. Because
      of these biases, the source of the cases must be taken into consideration when
      investigators are trying to synthesize the widely variable results of studies
      that have estimated the genetic contribution to ET.

PMID- 11295790
TI  - History of chorea: part 3 of the MDS-sponsored history of movement disorders
      exhibit, Barcelona, June 2000.

PMID- 11295791
TI  - History of dystonia: part 4 of the MDS-sponsored history of movement disorders
      exhibit, Barcelona, June, 2000.

PMID- 11295792
TI  - History of tic disorders and Gilles de la Tourette syndrome: part 5 of the MDS
      sponsored history of movement disorders exhibit, Barcelona, June 2000.

PMID- 11295793
TI  - Hemi-parkinsonism due to a midbrain arteriovenous malformation: dopamine
      transporter imaging.

PMID- 11295794
TI  - Oculogyric-like crises in a 92-year-old woman with vascular Parkinsonism.

PMID- 11295795
TI  - Case with both multiple system atrophy and primary progressive multiple sclerosis
      with discussion of the difficulty in their differential diagnosis.

PMID- 11295796
TI  - Camptocormia secondary to early amyotrophic lateral sclerosis.

PMID- 11295797
TI  - Catatonia or abulia? A difficult differential diagnosis.

PMID- 11295798
TI  - Eighty-nine-year-old man with generalised chorea and basal ganglia
      mineralization.

PMID- 11295800
TI  - Oculomotor focal dystonia.

PMID- 11295799
TI  - New nonsense mutation in the GTP-cyclohydrolase I gene in L-DOPA responsive
      dystonia-parkinsonism.

PMID- 11295801
TI  - Intrafamilial heterogeneity of facial hyperkinesias: chance association of tics,
      cranial dystonia, and Huntington's disease?

PMID- 11295802
TI  - Delayed-onset dystonia associated with 3-oxothiolase deficiency.

PMID- 11295803
TI  - Gait freezing and falling related to subthalamic stimulation in patients with a
      previous pallidotomy.

PMID- 11295804
TI  - Myoclonic tremor in patients with parkinsonian-type multiple system atrophy.

PMID- 11295807
TI  - International medical workshop covering progressive supranuclear palsy, Multiple
      System Atrophy and cortico basal degeneration.

PMID- 11295808
TI  - Organ preservation with radiotherapy for T1-T2 carcinoma of the pyriform sinus.
AB  - PURPOSE: To report long-term results using radiotherapy with or without a planned
      neck dissection for T1-T2 carcinoma of the pyriform sinus. METHODS: An analysis
      of 101 patients treated at the University of Florida with RT with or without a
      planned neck dissection for organ preservation. RESULTS: The 5-year local control
      rates after RT were 90% for T1 cancers and 80% for T2 lesions. The only parameter
      that significantly influenced local control in univariate analyses was apex
      involvement for T1 tumors. Multivariate analysis revealed no parameter that
      significantly affected local control. Cause-specific survival rates at 5 years
      were as follows: stage I-II, 96%; stage III, 62%; stage IVA, 49%; and stage IVB,
      33%. The absolute survival rates were as follows: stage I, 57%; stage II, 61%;
      stage III, 41%; stage IVA, 29%; and stage IVB, 25%. Moderate to severe long-term
      complications developed in 12% of patients. CONCLUSIONS: RT alone or combined
      with a planned neck dissection resulted in local control with larynx preservation
      in a high proportion of patients. The chance of cure is comparable to that
      observed after conservation surgery, and the risk of major complications is
      lower. The addition of adjuvant chemotherapy is unlikely to improve the
      probability of organ preservation, but might improve locoregional control for
      patients with advanced nodal disease.

PMID- 11295809
TI  - Definitive radiotherapy in the management of chemodectomas arising in the
      temporal bone, carotid body, and glomus vagale.
AB  - PURPOSE: To evaluate the results of treatment for 71 patients with 80
      chemodectomas of the temporal bone, carotid body, or glomus vagale who were
      treated with radiation therapy (RT) alone (72 tumors in 71 patients) or subtotal
      resection and RT (8 tumors) at the University of Florida between 1968 and 1998.
      METHODS AND MATERIALS: Sixty-six lesions were previously untreated, whereas 14
      had undergone prior treatment (surgery, 11 lesions; RT, 1 lesion; or both, 2
      lesions) and were treated for locally recurrent disease. All three patients who
      received prior RT had been treated at other institutions. Patients had minimum
      follow-up times as follows: 2 years, 66 patients (93%); 5 years, 53 patients
      (75%); 10 years, 37 patients (52%); 15 years, 29 patients (41%); 20 years, 18
      patients (25%); 25 years, 12 patients (17%); and 30 years, 4 patients (6%).
      RESULTS: There were five local recurrences at 2.6 years, 4.6 years, 5.3 years,
      8.3 years, and 18.8 years, respectively. Four were in glomus jugulare tumors and
      one was a carotid body tumor. Two of the four patients with glomus jugulare
      failures were salvaged, one with stereotactic radiosurgery and one with surgery
      and postoperative RT at another institution. Two of the five recurrences had been
      treated previously at other institutions with RT and/or surgery. Treatment for a
      third recurrence was discontinued, against medical advice, before receiving the
      prescribed dose. There were, therefore, only 2 failures in 65 previously
      untreated lesions receiving the prescribed course of RT. The overall crude local
      control rate for all 80 lesions was 94%, with an ultimate local control rate of
      96% after salvage treatment. The incidence of treatment-related complications was
      low. CONCLUSIONS: Irradiation offers a high probability of tumor control with
      relatively minimal risks for patients with chemodectomas of the temporal bone and
      neck. There were no severe treatment complications.

PMID- 11295810
TI  - Pain as sign of recurrent disease in head and neck squamous cell carcinoma.
AB  - BACKGROUND: The role of pain in head and neck cancer is seldom addressed. This
      retrospective study examined in a group of 190 curatively treated patients to
      what extent pain complaints should be considered to be the first sign of
      recurrent disease. METHODS: The research population exists of 95 patients with a
      recurrent head and neck carcinoma and control group matched for age, gender,
      primary tumor, and duration of follow-up. RESULTS: Of the patients with proven
      recurrent disease, 70% reported pain complaints as the first symptom. In 35% of
      these cases, the complaints concerned referred pain, whereas in 65% localized
      pain complaints in the head and neck were registered. The median interval between
      reporting localized pain complaints and histologic confirmation of recurrence was
      4 months. In the case of referred pain, this delay was 2.5 months. No
      statistically significant correlation between pain complaints and site of
      recurrence could be demonstrated. Only 2% of the control group reported pain
      complaints. CONCLUSIONS: This study confirms that each pain complaint after
      intentional curative treatment should be regarded as a warning sign. Recurrence
      of disease without preceding pain complaints (30%) emphasizes the importance of a
      thorough follow-up.

PMID- 11295811
TI  - Preoperative risk assessment for gastrostomy tube placement in head and neck
      cancer patients.
AB  - BACKGROUND: The presentation and definitive surgical treatment of head and neck
      malignancies have varying impact on postoperative recovery and return of
      swallowing function, which heretofore has not been well defined. METHODS: We
      performed a retrospective chart review of 142 patients who underwent extirpative
      surgery for head and neck cancer. RESULTS: Factors significantly associated with
      the need for long-term postoperative nutritional support (p < .05) included heavy
      alcohol use, tongue base involvement and surgery, pharyngectomy, composite
      resection, reconstruction with a myocutaneous flap, radiation therapy, tumor
      size, and moderately-to-poorly differentiated histology. Heavy alcohol users were
      at an absolute risk for gastrostomy tube dependence; patients who underwent
      radiation therapy, flap reconstruction, tongue base resection, and pharyngectomy
      were at a two to sevenfold increased risk for gastrostomy tube dependence,
      respectively. CONCLUSIONS: High-risk patients based on these criteria should
      receive a feeding gastrostomy at the time of their initial surgical therapy.

PMID- 11295812
TI  - The buccal fat pad flap in oral reconstruction.
AB  - BACKGROUND: The aim of this study is to describe the surgical technique,
      indications, advantages, and possible complications of the buccal fat pad flap
      and to report our clinical experience with this flap for intraoral reconstruction
      after tumor removal. METHODS: The flap has been used to reconstruct oral defects
      after tumor resection in 32 patients, who have been retrospectively analyzed.
      RESULTS: Adequate closure of the defect was achieved during surgery in all cases.
      In one case, there was partial loss of the flap; this was treated conservatively.
      In five cases there was some retraction in the reconstructed area. CONCLUSIONS:
      Buccal fat pad as a flap offers an adequate reconstructive option to be born in
      mind when reconstructing small to medium defects in the oral cavity. It is a
      simple and quick surgical technique with a low incidence of complications.

PMID- 11295813
TI  - Quality of life and oral function in patients treated with radiation therapy for
      head and neck cancer.
AB  - BACKGROUND: Multiple oral complaints develop during radiation therapy for head
      and neck cancer, and quality of life is affected after treatment. The purpose of
      this investigation was to assess the quality of life, oral function, and oral
      symptoms in a cohort of patients during and after radiation therapy. METHODS: A
      general quality of life survey (the European Organization for Research and
      Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), with an
      added oral symptom and function scale was administered to a consecutive series of
      patients who received radiation therapy for head and neck malignant disease.
      Patients completed surveys at the beginning of radiation therapy, immediately
      after, and 6 months after treatment. RESULTS AND DISCUSSION: The questionnaire
      used in this study provides increased information regarding the oral and dental
      function that is frequently affected by radiation therapy. Results of this study
      indicate the need to determine oral dysfunction after head and neck cancer
      therapy, so that the most predictable cure or best palliation of the malignancy
      with the least impact on oral function and quality of life is chosen. Oral
      complications during and after radiation therapy for head and neck cancer are
      common and affect quality of life. Oral QOL does not return to pretreatment
      levels by 6 months after radiation therapy. This study supports the use of a
      general function scale such as the EORTC questionnaire with the addition of
      disease/site-specific scales to provide data on outcomes of therapy and on the
      complications associated with therapy. The EORTC QLQ 30 questionnaire with the
      oral assessment addendum provides a measure of the quality of life and oral
      function in head and neck cancer patients and may provide useful outcome measures
      for assessment of oral care prevention and management strategies in these patient
      populations. The results show that the questionnaire is responsive to change
      throughout the course of radiation therapy for head and neck cancer.

PMID- 11295814
TI  - Atypical fibroxanthoma of the scalp.
AB  - BACKGROUND: Atypical fibroxanthoma occurs most frequently in the head and neck
      region of the elderly. Previous reports have identified that the condition
      usually arises at the following sites: the nose, cheeks, forehead, and the ears;
      its development at other sites is unusual. METHOD: We report a series of 10 cases
      with lesions all occurring at an apparently unusual site, the scalp, over a 10
      year period. We compared the clinical and histologic appearances and behavior of
      this series with the existing reports of these lesions elsewhere in the head and
      neck region to investigate whether there were differences with those occurring at
      a conventional site. RESULTS: Despite the identification of a range of clinical
      and histologic findings in our cases, we were unable to find any significant
      differences with those arising at a conventional site. CONCLUSION: This
      clustering of cases at an apparently unusual site leads us to propose that this
      condition occurs more commonly on the scalp than current literature suggests. The
      possibility of its development at this site should be remembered by head and neck
      surgeons in their differential diagnosis of exophytic lesions of the scalp.

PMID- 11295815
TI  - Effects of lingual gestures on blood flow into the tongue: a pilot study.
AB  - BACKGROUND: Reduced blood flow has been hypothesized to be a major factor in the
      formation of postradiation fibrosis. This study examined Doppler ultrasonography
      as a technique to detect changes in blood flow into the tongue during selected
      lingual gestures, /t/ and /k/. METHODS: Six normal subjects, three young men
      (mean age, 26 years) and three older men (mean age, 66 years) were examined in an
      upright position using Doppler ultrasound imaging of the external carotid artery
      just below the lingual artery. Measurements were made with a standardized
      segmentation technique before and after three repetitions of four speech
      production gestures /t/ and /k/, each with natural and maximal force. RESULTS:
      Blood flow peak systole increased significantly after the speech gestures (p <
      .001). Pooled before and after gesture values for older subjects were
      significantly lower than those for younger subjects (p < or = .05). CONCLUSIONS:
      Ultrasonography is a clinically useful technique for measuring blood flow during
      a dynamic gesture and may be useful for measuring effects of tumor treatment and
      in a lingual exercise program.

PMID- 11295816
TI  - Apoptosis and its clinical impact.
AB  - BACKGROUND: Apoptosis or programmed cell death is an orderly cascade that can be
      regulated and ultimately results in the demise of the cell. Induction of
      apoptosis can occur by various chemical and biologic agents. Initiation of
      apoptosis leads to activation of effector molecules particularly caspases. These
      proteases cleave distinct protein substrates, resulting in the morphologic
      changes seen in apoptosis. This form of cell death is involved in almost every
      physiologic and pathogenic process in the body. For this reason the ability to
      control apoptosis has important therapeutic ramifications. RESULTS: This article
      reviews the history of the investigation of apoptosis and summarizes the most
      important pathways and regulatory molecules involved in this process. The major
      regulators of apoptosis, including the Bcl-2, caspase, and inhibitor of apoptosis
      families, are examined. The two major apoptotic pathways, including the
      extrinsic/cell surface death receptor and the intrinsic/mitochondrial pathways,
      are discussed. A major emphasis is given to examining the relationship between
      apoptosis and certain disease processes. This review specifically focuses on the
      importance of apoptosis research in the development of new methods of management
      of cancer with an emphasis in head and neck oncology. CONCLUSIONS: Apoptosis is a
      rapidly growing field. The understanding of the mechanisms and effector molecules
      controlling this form of cell death is evolving. On the basis of increasing
      knowledge of how programmed cell death is regulated and the improvements in
      designing and developing gene therapies and chemicals that are more accurate in
      targeting specific molecules, the control of apoptosis will become more important
      in the clinical setting. This possibility will open the door for new therapeutic
      endeavors in many areas of medicine and specifically in the area of oncology.

PMID- 11295817
TI  - Isolated juvenile xanthogranuloma of the subglottis: case report.
AB  - BACKGROUND: Juvenile xanthogranulomatosis (JXG) is a relatively rare macrophage
      proliferative disorder. It usually presents as a localized cutaneous lesion but
      may affect other organs. Until now it has never been described in the subglottic
      region of the larynx. METHODS: We report the first case of juvenile
      xanthogranulomatosis (JXG) in the subglottis in a 3 year old child. RESULTS: The
      localization in the subglottis caused airway obstruction requiring tracheostomy
      to secure the airway. On the basis that most cutaneous lesions regress
      spontaneously the lesion was managed expectantly and regressed over a period of
      28 months allowing decannulation of the child. CONCLUSION: JXG should be
      considered in the differential diagnosis of subglottic lesions. Once the airway
      has been secured, JXG of the subglottis can be managed conservatively. Long-term
      follow-up is required because of the possibility of relapse at other sites.

PMID- 11295820
TI  - SNIPpets from the Third International Meeting on Single Nucleotide Polymorphism
      and Complex Genome Analysis, September 8-11, 2000, Taos, New Mexico, USA.

PMID- 11295818
TI  - Neck lymph node metastases to the posterior triangle apex: evaluation of clinical
      and histopathological risk factors.

PMID- 11295821
TI  - A semi-automated system for analysis and storage of SNPs.
AB  - The discovery of single nucleotide polymorphisms ( SNPs) is currently pursued
      with a tremendous effort. SNPs represent a rich source for molecular markers,
      since estimations predict six to seven million of these DNA variations in the
      human genome. A subset of these genetic variants is thought to have a pervasive
      impact on modern medicine, be it for the elucidation of differential
      pharmacological response or for the facilitated identification of genes involved
      in monogenetic and complex human diseases. Here we describe the overall process
      that leads to the set up of a SNP database. We describe a high-throughput
      sequencing assay for SNP discovery, automation of the dataflow from the DNA
      sequencer to the SNP analysis, and the tools to facilitate it. At the end of the
      process, a web-accessible interface collects the SNP information, which is
      processed in order to be written into the SNP database and to be available for
      end users who would like to select appropriate SNPs for their special screening
      needs.

PMID- 11295822
TI  - Allelic association with SNPs: metrics, populations, and the linkage
      disequilibrium map.
AB  - Comparison of different metrics, using three large samples of haplotypes from
      different populations, demonstrates that rho is the most efficient measure of
      association between pairs of single nucleotide polymorphisms (SNPs). Pairwise
      data can be modeled, using composite likelihood, to describe the decline in
      linkage disequilibrium with distance (the Malecot model). The evidence from more
      isolated populations (Finland, Sardinia) suggests that linkage disequilibrium
      extends to 427-893 kb but, even in samples representative of large heterogeneous
      populations, such as CEPH, the extent is 385 kb or greater. This suggests that
      isolated populations are not essential for linkage disequilibrium mapping of
      common diseases with SNPs. The in parameter of the Malecot model (recombination
      and time), evaluated at each SNP, indicates regions of the genome with extensive
      and less extensive disequilibrium (low and high values of in respectively). When
      plotted against the physical map, the regions with extensive and less extensive
      linkage disequilibrium may correspond to recombination cold and hot spots. This
      is discussed in relation to the Xq25 cytogenetic band and the HFE gene region.

PMID- 11295823
TI  - SNPs, protein structure, and disease.
AB  - Inherited disease susceptibility in humans is most commonly associated with
      single nucleotide polymorphisms (SNPs). The mechanisms by which this occurs are
      still poorly understood. We have analyzed the effect of a set of disease-causing
      missense mutations arising from SNPs, and a set of newly determined SNPs from the
      general population. Results of in vitro mutagenesis studies, together with the
      protein structural context of each mutation, are used to develop a model for
      assigning a mechanism of action of each mutation at the protein level. Ninety
      percent of the known disease-causing missense mutations examined fit this model,
      with the vast majority affecting protein stability, through a variety of energy
      related factors. In sharp contrast, over 70% of the population set are found to
      be neutral. The remaining 30% are potentially involved in polygenic disease.

PMID- 11295824
TI  - Maori origins, Y-chromosome haplotypes and implications for human history in the
      Pacific.
AB  - An assessment of 28 pertinent binary genetic markers on the non-recombining
      portion of the Y chromosome (NRY) in New Zealand Maori and other relevant
      populations has revealed a diverse genetic paternal heritage of extant Maori. A
      maximum parsimony phylogeny was constructed in which nine of the 25 possible
      binary haplotypes were observed. Although approximately 40% of the samples have
      haplotypes of unequivocal European origin, an equivalent number of samples have a
      single binary haplotype that is also observed in Indonesia and New Guinea,
      indicative of common indigenous Melanesian ancestry. The balance of the lineages
      has either typical East Asian signatures or alternative compositions consistent
      with their affinity to Melanesia or New Guinea. Molecular analysis of mtDNA
      variation confirms the presence of a single predominant characteristic Southeast
      Asian (9-bp deletion in the Region V) lineage. The Y-chromosome results support a
      pattern of complex interrelationships between Southeast Asia, Melanesia, and
      Polynesia, in contrast to mtDNA and linguistic data, which uphold a rapid and
      homogeneous Austronesian expansion. The Y-chromosome data highlight a distinctive
      gender-modulated pattern of differential gene flow in the history of Polynesia.

PMID- 11295825
TI  - Characterization of publicly available SNPs in the Korean population.
AB  - Single-nucleotide polymorphisms (SNPs) are the most abundant form of genetic
      variations and have a great potential for mapping studies of complex genetic
      traits. Currently a great deal of effort is invested in the identification of
      SNPs, and a large volume of data is already available through public databases
      (NCBI, NCI, WICGR, HGBASE). For an association mapping study, SNP allele
      frequencies in the population are critical. As an initial step toward
      construction of an SNP database of the Korean population, we have determined the
      allele frequencies of 300 cSNPs selected from the public database in 24
      individuals. Among the tested markers, approximately 23% did not show
      polymorphism in the population. The results suggest that the ethnic and
      population based differences should be considered in the selection of SNPs for
      the study of complex diseases with association mapping methods.

PMID- 11295826
TI  - Statistical multilocus methods for disequilibrium analysis in complex traits.
AB  - Hundreds of thousands of SNP markers are being generated with the purpose of
      carrying out case-control association studies for complex traits, which are
      thought to be due to multiple underlying susceptibility genes. The number of
      markers is typically much larger than the number of observations so that joint
      analysis of marker genotypes and their interactions is not feasible. We discuss a
      two-stage approach to first select a small subset of markers and then model the
      effects of the selected markers on disease. Examples of two procedures for marker
      selection are given with subsequent modeling of main and interaction effects. The
      approaches are applied to a data set with 89 SNPs in lieu of a genome screen with
      many more markers.

PMID- 11295827
TI  - Haplotyping and estimation of haplotype frequencies for closely linked biallelic
      multilocus genetic phenotypes including nuclear family information.
AB  - With the discovery of single nucleotide polymorphisms (SNP) along the genome,
      genotyping of large samples of biallelic multilocus genetic phenotypes for (fine)
      mapping of disease genes or for population studies has become standard practice.
      A genetic trait, however, is mainly caused by an underlying defective haplotype,
      and populations are best characterized by their haplotype frequencies. Therefore,
      it is essential to infer from the phase-unknown genetic phenotypes in a sample
      drawn from a population the haplotype frequencies in the population and the
      underlying haplotype pairs in the sample in order to find disease predisposing
      genes by some association or haplotype sharing algorithm. Haplotype frequencies
      and haplotype pairs are estimated via a maximum likelihood approach by a well
      known expectation maximization (EM) algorithm, adapting it to a large number (up
      to 30) of biallelic loci (SNP), and including nuclear family information, if
      available, into the analysis. Parents are treated as an independent sample from
      the population. Their genotyped offspring reduces the number of potential
      haplotype pairs for both parents, resulting in a higher accuracy of the
      estimation, and may also reduce computation time. In a series of simulations our
      approach of including nuclear family information has been tested against both the
      EM algorithm without nuclear family information and an alternative approach using
      GENEHUNTER for the haplotyping of the families, using the locus-by-locus allele
      counts of the sample. Our new approach is more precise in haplotyping in cases of
      a high number of heterozygous loci, whereas for a moderate number of heterozygous
      positions in the sample all three different approaches gave the same perfect
      results.

PMID- 11295828
TI  - High-throughput multiplex SNP genotyping with MALDI-TOF mass spectrometry:
      practice, problems and promise.
AB  - Single nucleotide polymorphisms (SNPs) are currently being identified and mapped
      at a remarkable pace, providing a rich genetic resource with vast potential for
      disease gene discovery, pharmacogenetics, and understanding the origins of modern
      humans. High-throughput, cost effective genotyping methods are essential in order
      to make the most advantageous and immediate use of these SNP data. We have
      incorporated the use of matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF) in our laboratory as a tool for
      differentiating genotypes based on the mass of the variant DNA sequence, and have
      utilized this method for production scale SNP genotyping. We have combined a 4
      microl PCR amplification reaction using 3 ng of genomic DNA with a secondary
      enzymatic reaction (mini-sequencing) containing oligonucleotide primers that
      anneal immediately upstream of the polymorphic site, dideoxynucleotides, and a
      thermostable polymerase used to extend the PCR product by a single base pair.
      Mass spectrometry (MS) analysis of mini-sequencing reactions was performed using
      a MALDI-TOF instrument (Voyager-DE, Perseptive Biosystems, Framingham, MA). We
      performed both single and multiplex PCR and mini-sequencing reactions, and
      genotyped seven different variant sites in a random sample of 989 individuals.
      Genotypes generated with MS methods were compared with genotypes produced using a
      5' exonuclease fluorescence-based assay (Taqman, Applied Biosystems, Foster City,
      CA) and a gel-based genotyping protocol. Because multiple polymorphisms can be
      detected in a single reaction, the MS technique provides a cost-effective and
      efficient method for high-throughput genotyping.

PMID- 11295829
TI  - Fluorescent microsphere-based readout technology for multiplexed human single
      nucleotide polymorphism analysis and bacterial identification.
AB  - Large-scale human genotyping requires technologies with a minimal number of
      steps, high accuracy, and the ability to automate at a reasonable cost. In this
      regard, we have developed a rapid, cost-effective readout method for single
      nucleotide polymorphism (SNP) genotyping that combines an easily automatable
      single-tube allele-specific primer extension (ASPE) with an efficient high
      throughput flow cytometric analysis performed on a Luminex 100 flow cytometer.
      This robust technique employs an ASPE reaction using PCR-derived target DNA
      containing the SNP and a pair of synthetic complementary capture probes that
      differ at their 3' end-nucleotide defining the alleles. Each capture probe has
      been synthesized to contain a unique 25-nucleotide identifying sequence (ZipCode)
      at its 5' end. An array of fluorescent microspheres, covalently coupled with
      complementary ZipCode sequences (cZipCodes), was hybridized to biotin-labeled
      ASPE reaction products, sequestering them for flow cytometric analysis. ASPE
      offers both an advantage of streamlining the SNP analysis protocol and an ability
      to perform multiplex SNP analysis on any mixture of allelic variants. All steps
      of the assay are simple additions of the solutions, incubations, and washes. This
      technique was used to assay 15 multiplexed SNPs on human chromosome 12 from 96
      patients. Comparison of the microsphere-based ASPE assay results to gel-based
      oligonucleotide ligation assay (OLA) results showed 99.2% agreement in genotype
      assignments. In addition, the microsphere-based multiplex SNPs assay system was
      adapted for the identification of bacterial samples by both ASPE and single base
      chain extension (SBCE) assays. A series of probes designed for different variable
      sites of bacterial 16S rDNA permitted multiplex analysis and generated species-
      or genus-specific patterns. Seventeen bacterial species representing a broad
      range of gram-negative and gram-positive bacteria were analyzed within 16
      variable sites of 16S rDNA sequence. The results were consistent with the
      published sequences and confirmed by direct DNA sequencing.

PMID- 11295830
TI  - Molecular basis of recessive congenital methemoglobinemia, types I and II: Exon
      skipping and three novel missense mutations in the NADH-cytochrome b5 reductase
      (diaphorase 1) gene.
AB  - Hereditary methemoglobinemia due to reduced nicotin amide adenine dinucleotide
      (NADH)-cytochrome b5 reductase (b5r) deficiency is classified into an erythrocyte
      type (I) and a generalized type (II). We investigated the b5r gene of three
      unrelated patients with types I and II and found four novel mutations. The
      patient with type I was homozygous for a c.535 G-->A exchange in exon 6 (A179T).
      The patients with type II were found to be homozygous for a c.757 G-->A
      transition in exon 9 (V253M) and compound heterozygous for two mutations,
      respectively. One allele presented a c.379 A-->G transition (M127V). The second
      allele carried a sequence difference at the invariant 3' splice-acceptor
      dinucleotide of intron 4 (IVS4-2A-->G) resulting in skipping of exon 5. To
      characterize a possible effect of this mutation on RNA metabolism, poly(A)(+) RNA
      was analyzed by RT-PCR and sequencing. The results show that RNA is made from the
      allele harboring the 3'-splice site mutation. Furthermore, western blot analysis
      revealed a complete absence of immunologically detectable b5r in skin fibroblasts
      of this patient. The compound heterozygosity for the splice site and the missense
      mutations apparently caused hereditary methemoglobinemia type II in this patient.
      Hum Mutat 17:348, 2001.

PMID- 11295831
TI  - Identification of novel WFS1 mutations in Italian children with Wolfram syndrome.
AB  - Six unrelated Italian children with Wolfram syndrome (WS) were analyzed for
      mutations in the WFS1. Four novel mutations (1387delCTCT, S443I, 1519del16, and
      IVS6+16g->a) were identified. In addition, we found two new, probably neutral
      changes (A684V and R708C). Other previously described variants were a
      heterozygous I333V in three alleles and the H611R in two. The 1519del16 mutation
      was carried by two patients whereas the CTCT deletion occurred in three subjects
      from two apparently unrelated families with WS. The current study expands the
      spectrum of mutations in WFS1 and represents the first molecular characterization
      of Italian WS patients.

PMID- 11295832
TI  - The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal
      dysplasia.
AB  - Mutations in ectodysplasin, the protein product of the EDA or ED1 gene, cause X
      linked anhidrotic ectodermal dysplasia. From sixteen families we have identified
      thirteen mutations, of which nine were novel: a deletion of the entire exon 1,
      altered splicing site in intron 7 (IVS-2A-->G) and in intron 9 (IVS9+8 C-->G),
      deletion of 8 bp (1967-1974 nt), four missense mutations (G255C, G255D, W274G,
      C332Y) and nonsense mutation W274X. Previously identified and the novel mutations
      form four clusters: 1) at the junction of the transmembrane and extracellular
      domains, 2) at a putative protease recognition site, possibly affecting cleavage
      of ectodysplasin, 3) at the trimerizing collagen-like domain, and 4) at regions
      of high homology to tumor necrosis factor domains. Truncating and splice site
      mutations occur within the proximal two-thirds of the protein. Our data suggest
      the functional importance of specific ectodysplasin domains. Hum Mutat 17:349,
      2001.

PMID- 11295833
TI  - Human GABA(B) receptor 1 gene: eight novel sequence variants.
AB  - GABA (gamma-aminobutyric acid) is the principal inhibitory neurotransmitter in
      the brain. The human GABA(B) receptor (GABBR1) maps to the human leukocyte
      antigen (HLA) region of chromosome 6. Its function and location in a
      susceptibility region for schizophrenia, epilepsy, and dyslexia make GABBR1 a
      candidate gene for neurobehavioral disorders. We report the characterization of
      GABBR1 gene mutations in 100 chromosomes from a mixed American population. Eleven
      distinct mutations were found, including two previously reported missense
      mutations (A20V and G489S) and a previously reported silent 1977 T>C transition.
      Here, we report four novel silent substitutions (39C>T, 1473T>C, 1476T>C,
      1545T>C) and four novel intron variants. These DNA variants may be useful in
      association and linkage studies of neurobehavioral disorders, and in
      pharmacogenetic studies of drugs targeting GABBR1.

PMID- 11295834
TI  - Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in
      patients with familial porphyria cutanea tarda (f-PCT).
AB  - In this work, we describe seven novel molecular defects in the uroporphyrinogen
      decarboxylase gene responsible for familial porphyria cutanea tarda in Italian
      subjects with reduced erythrocyte URO-D activity. Four of these molecular
      abnormalities (R142Q, L161Q, S219F, P235S) are missense mutations, one (Q206X) is
      a nonsense mutation, one (IVS8-1 G>C) is a splicing defect causing the exon 9
      deletion and one (1107 G>A) is located in the 3' untranslated region of UROD
      gene. All the amino acid substitutions fall in conserved regions in several
      organisms suggesting an important role in catalysis or in the protein structure
      stabilization. Three of these mutations have been detected in more than one
      subject. These results suggest a molecular heterogeneity at the UROD locus in
      Italian PCT patients although recurrent mutations have been identified.

PMID- 11295835
TI  - Haplotyping of wild type and I278T alleles of the human cystathionine beta
      synthase gene based on a cluster of novel SNPs in IVS12.
AB  - Homocystinuria is most frequently due to deficiency of cystathionine beta
      synthase (CBS). We identified IVS12 as a polymorphism hot spot of the human CBS
      gene and report five novel single nucleotide polymorphisms (SNPs): g.13514G>A,
      g.13617A>G, g.13715C>T, g.13800G>A, and g.13904C>T. Analyzing 50 control DNA
      samples of unaffected and unrelated subjects of German origin the observed
      frequencies of heterozygosity were 0.02, 0.36, 0.18, 0.36, and 0.36,
      respectively. These polymorphic markers were combined into four distinct IVS12
      haplotypes A1, A2, B1, and B2, revealing frequencies of 0.75, 0.01, 0.15, and
      0.09, respectively, with an observed overall frequency of heterozygosity at 0.38.
      This haplotype system and the SNP c.699 were employed in the analysis of ten
      alleles affected by the most prevalent CBS mutation, c.833T>C (exon 8; I278T). We
      found that the I278T alleles segregate with at least two distinct haplotypes
      characterized by upstream and downstream polymorphic sites instead of sharing a
      common ancestral haplotype. This was a remarkable finding even in patients with
      very similar ethnic background. The novel haplotype system may facilitate future
      studies on the evolution of the CBS gene and might be suited for genotyping of
      families affected by homocystinuria.

PMID- 11295836
TI  - Identification of a novel COCH mutation, I109N, highlights the similar clinical
      features observed in DFNA9 families.
AB  - Hereditary hearing loss is a heterogeneous condition at both the genetic and
      clinical levels. We have recruited an Australian family with dominant
      sensorineural nonsyndromic late onset hearing loss. The hearing loss typically
      begins in the second or third decade of life as a high frequency loss which
      progresses to a severe to profound loss by the sixth to seventh decade. All
      affected family members presented with concomitant vestibular dysfunction.
      Vertigo is a less common feature. The causative gene in this family was
      identified as COCH which lies within the DFNA9 interval. We identified a new
      point mutation, 253 T>A, in the coding region of the COCH gene, changing the
      isoleucine 109 to an asparagine (I109N). This is a non-conservative change of an
      amino acid that is identical in the human, mouse and chicken sequences. The
      mutation was identified in all affected individuals (n=13) and all were
      heterozygotes. Hearing loss in this family is clinically similar to that observed
      in ten other DFNA9 families. However, there are some differences in the age of
      onset and the extent of vestibular involvement. The remarkable clinical
      uniformity observed between DFNA9 families is intriguing especially in light of
      the great phenotypic variability observed with some of the other hearing loss
      genes. Hum Mutat 117:351, 2001.

PMID- 11295837
TI  - Mutation analysis of the tyrosinase gene in oculocutaneous albinism.
AB  - Type I oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by
      the reduction or the absence of tyrosinase (TYR) activity in melanocytes of the
      skin, hair and eyes. Here we report an analysis of 45 patients with OCA. We found
      five novel mutations in the tyrosinase gene involved in the pathogenesis of
      oculocutaneous albinism type IA or type IB (OCA-1A/B) in five unrelated patients.
      Three mutations are missense mutations (G109R, P205T and H256Y) and two are
      nucleotide deletions (336-337delCA and 678-680delAGG). One patient is homozygous
      for the previously known V275F mutation but has an extremely mild OCA phenotype
      and has no eye features typical of OCA. In several patients we discovered only
      one or even no mutation in the coding sequence of the TYR gene. Thus, this
      disease may also result from mutations in non coding regions of the gene or in
      another gene involved in the biosynthesis of melanin. Hum Mutat 17:352, 2001.

PMID- 11295838
TI  - Identification of a novel polymorphism (IVS6-33C->G) and two novel rare variants
      (IVS6-42delT and IVS6-43delA) in RPE65 gene.

PMID- 11295839
TI  - Two polymorphic mutations (c2331A>C and IVS11+142insAGAAATTTTAAGTCTT) in the
      human peroxin 1 gene (PEX1).

PMID- 11295840
TI  - Identification of a novel de novo mutation (G373D) in the alpha-galactosidase A
      gene (GLA) in a patient affected with Fabry disease.

PMID- 11295841
TI  - A rare variant, I852M, of the RET proto-oncogene in a patient with medullary
      thyroid carcinoma at age 20 years.

PMID- 11295842
TI  - Identification of a polymorphism (D168N) in the XRP2 gene in Chinese.

PMID- 11295843
TI  - Two novel LDL receptor mutations in familial hypercholesterolemia: C122Y and
      E296X.

PMID- 11295844
TI  - Population analysis of g.2488delG and three novel polymorphisms (g.4497G>A,
      g.4503G>A and g.2319G>A) in the plasminogen activator inhibitor 1 (PAI-1) gene.

PMID- 11295845
TI  - Two novel polymorphisms g.1715G>A (A496T) and g.1838G>A (3'UTR), and the
      g.1548G>A (E469K) variant in the intercellular adhesion molecule 1 (ICAM1) gene:
      Distribution in the Japanese and European American populations.

PMID- 11295846
TI  - A novel b(1-4)galactosyltransferase gene silent mutation (594C>T) associated with
      Hutchinson-Gilford progeria.

PMID- 11295847
TI  - Detection of known and two novel (M331I and R464S) missense mutations in the
      human CYP1A1 gene in a French Caucasian population.

PMID- 11295848
TI  - Five novel natural allelic variants-951A>C, 1042G>A (D348N), 1156A>T (I386F),
      1217G>A (C406Y) and 1291C>T (C431Y)-of the human CYP1A2 gene in a French
      Caucasian population.

PMID- 11295849
TI  - A novel nonsense mutation (Q1291X) in exon 20 of CFTR (ABCC7) gene.

PMID- 11295851
TI  - A C-arm fluoroscopy-guided progressive cut refinement strategy using a surgical
      robot.
AB  - We describe a new method to cut a precise, high-quality femoral cavity in
      Revision Total Hip Replacement surgery (RTHR) using a surgical robot and an intra
      operative C-arm fluoroscope. With respect to previous approaches, our method
      contains several new features. (1) We describe a novel checkerboard plate
      designed to correct the geometric distortion within fluoroscopic images. Unlike
      previous distortion correction devices, the plate does not completely obscure any
      part of the image, and the distortion correction algorithm works well even when
      there are some overlaid objects in the field of view. (2) Also included are a
      novel corkscrew fiducial object designed to be integrated with the robot end
      effector, and a 6D pose estimation algorithm based on the two-dimensional (2D)
      projection of the corkscrew, used in robot-imager registration and imager co
      registration. (3) In addition, we develop a cavity location algorithm, which
      utilizes image subtraction and 2D anatomy contour registration techniques. (4)
      Finally, we propose a progressive cut refinement strategy, which progressively
      improves the robot registration during the procedure. We have conducted several
      experiments, in both simulated and in vitro environments. The results indicate
      that our strategy is a promising method for precise orthopedic procedures like
      total hip replacement.

PMID- 11295850
TI  - A new polymorphism (c28C>A) of EXT2 gene identified in a Taiwan Chinese family.

PMID- 11295852
TI  - Surgical navigation based on fluoroscopy--clinical application for computer
      assisted distal locking of intramedullary implants.
AB  - OBJECTIVE: Fluoroscopy is used to guide surgical instruments during orthopedic
      procedures. Radiation exposure and lack of spatial information are drawbacks of
      this method. Improvements are expected when fluoroscopy-based surgical navigation
      is used for intraoperative guidance, e.g., in computer-assisted distal locking of
      intramedullary implants. PATIENTS AND METHODS: The method was applied to 42
      interlocking procedures during implantation of the short proximal femoral nail in
      27 patients with pertrochanteric femoral fractures. Precision of interlocking,
      exposure time, operating time, and number of personnel required for computer
      assisted distal locking were recorded. RESULTS: One misplaced interlocking screw
      was observed (2.3%), and contact between the drill bit and the nail during
      drilling was noticed in 8 cases (19%). The average exposure time was 16 seconds
      (range 4-42 seconds), and the procedure took an average of 43 min (range 20-70
      min). The number of persons required for computer-assisted distal locking was
      reduced from three to one within the course of the study. CONCLUSIONS:
      Fluoroscopy-based surgical navigation provided precise intraoperative guidance
      for computer-assisted distal locking with minimal use of fluoroscopy. The complex
      system and related procedure times may be drawbacks in this application. Clinical
      studies are underway to define implants and surgical procedures where
      intraoperative guidance by fluoroscopy-based surgical navigation is beneficial
      for the patient and/or surgeon.

PMID- 11295853
TI  - A software system for interventional magnetic resonance image-guided prostate
      brachytherapy.
AB  - OBJECTIVE: Current prostatic brachytherapy implant procedures use ultrasound
      imaging for geometric guidance during surgery, with pre-surgical planning based
      on ultrasound images and post-surgical dosimetry based on computed tomography
      (CT). This procedure suffers from the poor soft-tissue contrast of ultrasound and
      CT and problems inherent in the repositioning of the patient at surgery. We have
      designed and implemented an integrated real-time imaging and treatment-planning
      software system that combines the superior soft-tissue contrast of magnetic
      resonance (MR) images with the real-time acquisition of those images for
      localization, verification, and dosimetric purposes. The system permits the
      surgeon and patient to complete all phases of treatment in one setting. MATERIALS
      AND METHODS: We utilize an intra-operative MR unit that permits real-time imaging
      and stereotactic localization during a surgical procedure. Our software system
      integrates with the unit and features (i) a calibration schema to calibrate the
      prostatic surgical implant template within the unit, (ii) full volumetric data
      acquisition of the prostate, (iii) interactive three-dimensional (3D) treatment
      planning with volumetric dose evaluation, and (iv) geometric and dosimetric
      feedback during the surgical procedure. We utilize a software architecture that
      uses mediators between the abstract data types, or objects. These mediators
      communicate state changes in individual objects (e.g., a change in a catheter
      position) to other objects (e.g., a dose-volume histogram) that depend on these
      changes. A consistent 3D representation of the treatment volumes allows
      interactive reconstruction of the volumes on arbitrary MR image sections and real
      time dose computations. RESULTS: We have successfully implemented the system
      clinically and have treated 143 patients (as of August 2000). The system supports
      four clinical phases. The first consists of calibrating the implant template with
      respect to the patient's anatomy and the MR unit. The second consists of
      acquiring a complete volumetric MR data set of the prostatic volume. The third
      consists of delineating the treatment volume (often a sub-volume of the prostate)
      and the dose-limiting critical volumes. These volumes are used in determining the
      surgical treatment plan based on catheter and seed placement in the prostate and
      a dosimetric evaluation of all volumes. The final phase consists of implanting
      the catheters with the radioactive seeds, where each catheter is imaged and
      compared to the planned position of the catheter, thus allowing a direct
      comparison, and possible adjustment, of the implanted versus planned catheter
      position. CONCLUSIONS: The system is highly interactive, and has great
      flexibility in its design, maintainability, and clinical practice. The system
      provides an efficient model to support the surgical procedure. The system
      significantly improves the diagnostic information provided to the clinician and
      the treatment planner and the geometric accuracy of the surgical procedure
      compared to ultrasound procedures. The system allows excellent critical structure
      sparing, both through interactive placement of the catheters with high geometric
      accuracy and through the definition of the actual sub-prostatic volumes possible
      with MR.

PMID- 11295854
TI  - Registration of functional and anatomical MRI: accuracy assessment and
      application in navigated neurosurgery.
AB  - OBJECTIVE: A procedure for acquisition, automated registration, and fusion of
      functional and anatomical magnetic resonance images is presented. Its accuracy is
      quantitatively assessed using a publicly available gold standard. A patient case
      is used to illustrate the technique's clinical usefulness in image-guided
      neurosurgery. MATERIALS AND METHODS: Before and after functional MRI (fMRI)
      acquisition, additional anatomical images were acquired at spatial locations
      identical to those of the functional images (5-10 slices) for the purpose of
      voxel-based image registration. Registration accuracy of the anatomical volumes
      and high-resolution 3D MRI volumes (MP-RAGE imaging) was quantified using adapted
      data (8 patients) originating from the Vanderbilt Retrospective Registration
      Evaluation Project (NIH project 1 R01 NS33926-02). Selecting three subsets of
      slices from that data (5 slices/6 mm slice distance, 10 slices/3 mm distance, and
      10 slices/6 mm distance), the small number of images available from fMRI
      acquisition was taken into account. Accuracies in registering these sparse data
      sets were then compared to the accuracy achieved using complete data. For
      clinical patient data (16 patients), fMRI images were fused with MP-RAGE images,
      thereby integrating anatomical images with information about the locations of
      functional areas. The resulting images were used for planning and navigation
      during tumor resections using an operating microscope (MKM, Zeiss). RESULTS:
      Quantitative analysis showed no loss of registration accuracy due to a reduced
      number of slices, regardless of whether 5 or 10 slices were used. For small
      volume coverage in the anatomical images (thickness 24 mm), registration of one
      patient failed, and this could easily be identified by visual inspection. No
      failures were experienced when 54 mm was covered. In the clinical environment,
      all 16 interventions using fused fMRI and MRI data were successful. CONCLUSIONS:
      Automatic registration of functional and high-resolution anatomical MRI was found
      to be sufficiently accurate and reliable for use in stereotactic neurosurgery.

PMID- 11295855
TI  - Is the head position during preoperative image data acquisition essential for the
      accuracy of navigated brain tumor surgery?
AB  - OBJECTIVE: To analyze the influence of head positioning during preoperative image
      data acquisition on intraoperative accuracy of modern neuronavigation systems.
      MATERIAL AND METHODS: All measurements were performed preoperatively before
      opening the head. In 24 patients, preoperative MR image data acquisition was
      performed twice on a 0.5 T scanner using a contrast-enhanced T1-weighted
      sequence; first in the neutral head position, and thereafter in the surgical head
      position for pterional craniotomy. For both data sets, the Sylvian fissure, the
      central sulcus, and the superior and inferior temporal sulci were depicted on the
      patient's scalp using the frameless neuronavigation system EasyGuide Neurotrade
      mark. At the beginning of surgery, with the head fixed in a Mayfield clamp and an
      articulated instrument holder being used for fixation of the navigation system's
      pointer, the distances of 10 correlating points of the sulci for the two data
      sets were measured. To evaluate the accuracy of the navigation system in this
      experimental set-up, a phantom study was also performed. RESULTS: The phantom
      study revealed a mean inaccuracy of 1.6 mm (range 0.1-2.3 mm, standard deviation
      0.6 mm). The patient study revealed a mean inaccuracy of 1.8 mm (range 0.4-2.8
      mm, standard deviation 0.5 mm). CONCLUSIONS: The data suggest that the
      positioning of the patient's head during preoperative imaging plays no relevant
      role in intraoperative accuracy of neuronavigation. However, further studies and
      a larger number of patients with various pathologies in different regions of the
      brain are necessary to obtain a better understanding of the problem of brain
      shift in neuronavigation due to patient positioning alone, and to avoid procedure
      related operative morbidity.

PMID- 11295856
TI  - Clara-cell hyperplasia after quartz and coal-dust instillation in rat lung.
AB  - Bronchiolo-alveolar hyperplasia of type II cells in rat lungs after particle
      exposure is a well-known preneoplastic lesion. The Clara cell, stem cell of the
      bronchiolar epithelium and the main carrier of cytochrome P-450 isoenzyme system
      in the lung, has barely been evaluated with regard to this effect. The aim of
      this study was to examine Clara-cell hyperplasia after particle exposure and to
      characterize cell proliferation and its normal function. Female Wistar rats were
      intratracheally instilled with coal dust samples of variable quartz content,
      quartz (DQ12), titanium dioxide, or saline solution containing 0.5% Tween 80.
      After 126-129 wk, all coal mine dust- and quartz-exposed animals developed Clara
      cell hyperplasia: up to 0.48% of the total lung area, which was significantly
      increased compared to titanium dioxide (p <.05) and control (p <.03) animals.
      Proliferation and hyperplasia of bronchiolar Clara cells by coal dusts was
      independent of their quartz content. The lack of proliferating cell nuclear
      antigen staining in most of the hyperplastic Clara cells suggests that following
      damage of alveolar epithelial cells, Clara cells migrate in and remodulate the
      alveolar epithelium. After the migration they keep their function in the
      xenobiotic metabolism, as shown by expansion of CYP2E1 active Clara cells. The
      minor development of Clara-cell hyperplasia in titanium dioxide-treated rats
      indicates that this is not a general particle effect, and is possibly due to its
      lower toxicity to epithelial cells.

PMID- 11295857
TI  - Uptake, tissue distribution, and fate of inhaled carbon tetrachloride: comparison
      of rat, mouse, and hamster.
AB  - Carbon tetrachloride is hepatotoxic in rats, mice, and hamsters. However, rats
      are less sensitive to the hepatotoxic effects of CCl(4) than the other two
      species. The purpose of this study was to compare the uptake, tissue
      distribution, and elimination of CCl(4) by these three rodent species. Groups of
      20 F344/Crl BR rats, B6C3F(1) mice, and Syrian hamsters were exposed by nose-only
      inhalation for 4 h to 20 ppm (14)C-labeled CCl(4). The fate of (14)C was followed
      in tissues, excreta, and exhaled breath for 48 h after the exposure. At the end
      of the exposure, concentrations of CCl(4) equivalents (CE) in tissue were highest
      in liver of rats and mice, but highest in fat for rats. The liver received the
      highest dose of CCl(4) equivalents with the following species ranking: mouse >
      hamster > rat. Patterns of CE elimination were species and tissue dependent, with
      the majority of elimination occurring within 48 h after exposure. Rats eliminated
      less radioactivity associated with metabolism ((14)CO(2), urine and feces) and
      more radioactivity associated with parent compound (exhaled activity trapped on
      charcoal) than did mice or hamsters. The results indicate that ranking of species
      sensitivity to the hepatotoxic effects of inhaled CCl(4) correlates with CE dose
      to liver and with the ability to metabolize CCl(4).

PMID- 11295858
TI  - Ischemic tolerance of the heart by adaptation to chronic hypoxia is suppressed by
      high subchronic carbon monoxide exposure.
AB  - This study was designed to investigate whether exposure to carbon monoxide (CO)
      could alter the ischemic tolerance induced by chronic hypoxia. We aimed to
      determine whether chronic hypoxia-induced cardiovascular adaptation was modified
      during the return to normoxia or by subchronic CO exposure. The degree of
      resistance to an in vitro transient ischemia was measured, using the Langendorff
      method, in hearts from rats previously exposed to chronic hypoxic hypoxia and/or
      subchronic CO exposure to 600 ppm. Chronic hypoxia decreased ischemic contracture
      (15.6 +/- 04.9 vs. 60.8 +/- 07.7%) and improved both contractile recovery (59.6
      +/- 07.3 vs. 21.8 +/- 06.8%) and ventricular arrhythmia during reperfusion (0 vs.
      45%) compared to a control normoxic group. However, in our chronic hypoxia
      regression model many parameters returned near to control values except for the
      persistence of cardiomegaly, a significant decrease in both ischemic contracture
      (22.0 +/- 04.9 vs. 60.8 +/- 07.7%), and ventricular tachycardia (25 vs. 45%). CO
      exposure alone increased the coronary flow and improved both contractile recovery
      (42.6 +/- 7.2 vs. 21.8 +/- 6.8%) and ventricular arrhythmia (16.7 vs. 45%)
      without altering the action potential shape. These two models causing tissue
      hypoxia induced the same degree of polycythemia or cardiomegaly and provided
      similar ischemic tolerance. CO exposure after chronic hypoxia exacerbated
      ischemic contracture (69.3 +/- 10.5 vs. 22.0 +/- 14.5%) and ventricular
      tachycardia incidence (100 vs. 50%) but with significant alteration in
      contractile recovery (12.7 +/- 10.5%) compared to the chronic hypoxia or CO
      exposure. Thus, CO exposure completely suppressed the chronic hypoxia-induced
      ischemic tolerance.

PMID- 11295859
TI  - Induction of cytotoxicity and production of inflammatory mediators in raw264.7
      macrophages by spores grown on six different plasterboards.
AB  - Dampness and microbial growth in buildings are associated with respiratory
      symptoms in the occupants, but details of the phenomenon are not sufficiently
      understood. The current study examined the effects of growth conditions provided
      by six plasterboards on cytotoxicity and inflammatory potential of the spores of
      Streptomyces californicus, Penicillium spinulosum, Aspergillus versicolor, and
      Stachybotrys chartarum. The microbes were isolated from mold problem buildings
      and thereafter grown on six different plasterboards. The spores were harvested,
      applied to RAW264.7 macrophages (10(4), 10(5), 10(6) spores/10(6) cells), and
      evaluated 24 h after exposure for the ability to cause cytotoxicity and to
      stimulate production of nitric oxide (NO), interleukin-1 beta (IL-1beta), tumor
      necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6). The data indicate
      clear differences between spores of different microbes in their ability to induce
      the production of these inflammatory mediators and to cause cell death in
      macrophages. Also, for each microbe, the induction ability specifically depended
      on the brand of plasterboard. The spores of Streptomyces californicus collected
      from all plasterboards were the most potent at inducing NO and cytokine
      production. Cytotoxicity caused by P. spinulosum and Streptomyces californicus
      spores was consistent with NO, IL-1beta and IL-6 production induced by those
      microbes. However, the production of these inflammatory mediators by the spores
      of Stachybotrys chartarum was not parallel to their ability to cause cell death.
      The low productions of NO and cytokines were associated with high cytotoxicity
      caused by the spores of the A. versicolor. These data suggest that growth
      condition of microbes on different plasterboards affect the ability of microbial
      spores to induce inflammatory responses and cytotoxicity in macrophages.

PMID- 11295860
TI  - Inhalation studies with the Gottingen minipig.
AB  - A method for inhalative exposure of minipigs to aerosols and gases has been
      developed. Minipigs are exposed via mask inhalation to the test substance using a
      computer-controlled exposure system that permits simultaneous exposure of groups
      of four animals in parallel to different controlled dose levels. We studied
      inhalation treatment of verapamil, a cardiovascular drug, and show good
      absorption and favorable pharmacokinetics when compared with iv drug application.
      The results shown in this study encourage inhalation studies with the Gottingen
      minipig.

PMID- 11295861
TI  - Fluid dynamics in airway bifurcations: I. Primary flows.
AB  - The subject of fluid dynamics within human airways is of great importance for the
      risk assessment of air pollutants (inhalation toxicology) and the targeted
      delivery of inhaled pharmacologic drugs (aerosol therapy). As cited herein,
      experimental investigations of flow patterns have been performed on airway models
      and casts by a number of investigators. We have simulated flow patterns in human
      lung bifurcations and compared the results with the experimental data of Schreck
      (1972). The theoretical analyses were performed using a third-party software
      package, FIDAP, on the Cray T90 supercomputer. This effort is part of a
      systematic investigation where the effects of inlet conditions, Reynolds numbers,
      and dimensions and orientations of airways were addressed. This article focuses
      on primary flows using convective motion and isovelocity contour formats to
      describe fluid dynamics; subsequent articles in this issue consider secondary
      currents (Part II) and localized conditions (Part III). The agreement between
      calculated and measured results, for laminar flows with either parabolic or blunt
      inlet conditions to the bifurcations, was very good. To our knowledge, this work
      is the first to present such detailed comparisons of theoretical and experimental
      flow patterns in airway bifurcations. The agreement suggests that the
      methodologies can be employed to study factors affecting airflow patterns and
      particle behavior in human lungs.

PMID- 11295862
TI  - Fluid dynamics in airway bifurcations: II. Secondary currents.
AB  - As the second component of a systematic investigation on flows in bifurcations
      reported in this journal, this work focused on secondary currents. The first
      article addressed primary flows and the third discusses localized conditions
      (both in this issue). Secondary flow patterns were studied in two lung
      bifurcation models (Schreck, 1972) using FIDAP with the Cray T90 supercomputer.
      The currents were examined at different prescribed distances distal to the
      carina. Effects of inlet conditions, Reynolds numbers, and diameter ratios and
      orientations of airways were addressed. The secondary currents caused by the
      presence of the carina and inclination of the daughter tubes exhibited symmetric,
      multivortex patterns. The intensities of the secondary currents became stronger
      for larger Reynolds numbers and larger angles of bifurcation.

PMID- 11295863
TI  - Fluid dynamics in airway bifurcations: III. Localized flow conditions.
AB  - Localized flow conditions (e.g., backflows) in transition regions between parent
      and daughter airways of bifurcations were investigated using a computational
      fluid dynamics software code (FIDAP) with a Cray T90 supercomputer. The
      configurations of the bifurcations were based on Schreck s (1972) laboratory
      models. The flow intensities and spatial regions of reversed motion were
      simulated for different conditions. The effects of inlet velocity profiles,
      Reynolds numbers, and dimensions and orientations of airways were addressed. The
      computational results showed that backflow was increased for parabolic inlet
      conditions, larger Reynolds numbers, and larger daughter-to-parent diameter
      ratios. This article is the third in a systematic series addressed in this issue;
      the first addressed primary velocity patterns and the second discussed secondary
      currents.

PMID- 11295864
TI  - A nonhuman primate aerosol deposition model for toxicological and pharmaceutical
      studies.
AB  - Nonhuman primates may be used as human surrogates in inhalation exposure studies
      to assess either the (1) adverse health effects of airborne particulate matter or
      (2) therapeutic effects of aerosolized drugs and proteins. Mathematical models
      describing the behavior and fate of inhaled aerosols may be used to complement
      such laboratory investigations. For example, the optimal conditions, in terms of
      ventilatory parameters (e.g., breathing frequency and tidal volume) and aerosol
      characteristics (e.g., geometric size and density), necessary to target drug
      delivery to specific sites within the respiratory tract may be estimated a priori
      with models. In this work a mathematical description of the rhesus monkey (Macaca
      mulatta) lung is presented for use with an aerosol deposition model. Deposition
      patterns of 0.01- to 5-microm-diameter monodisperse aerosols within lungs were
      calculated for 3 monkey lung models (using different descriptions of alveolated
      regions) and compared to human lung results obtained using a previously validated
      mathematical model of deposition physics. Our findings suggest that there are
      significant differences between deposition patterns in monkeys and humans. The
      nonhuman primates had greater exposures to inhaled substances, particularly on
      the basis of deposition per unit airway surface area. However, the different
      alveolar volumes in the rhesus monkey models had only minor effects on aerosol
      dosimetry within those lungs. By being aware of such quantitative differences,
      investigators can employ the respective primate models (human and nonhuman) to
      more effectively design and interpret the results of future inhalation exposure
      experiments.

PMID- 11295865
TI  - Use of computational fluid dynamics models for dosimetry of inhaled gases in the
      nasal passages.
AB  - Computational fluid dynamics (CFD) models of the nasal passages of a rat, monkey,
      and human are being used (1) to determine important factors affecting nasal
      uptake, (2) to make interspecies dosimetric comparisons, (3) to provide detailed
      anatomical information for the rat, monkey, and human nasal passages, and (4) to
      provide estimates of regional air-phase mass transport coefficients (a measure of
      the resistance to gas transport from inhaled air to airway walls) in the nasal
      passages of all three species. For many inhaled materials, lesion location in the
      nose follows patterns that are both site and species specific. For reactive,
      water-soluble (Category 1) gases, regional uptake can be a major factor in
      determining lesion location. Since direct measurement of airflow and uptake is
      experimentally difficult, CFD models are used here to predict uptake patterns
      quantitatively in three-dimensional reconstructions of the F344 rat, rhesus
      monkey, and human nasal passages. In formaldehyde uptake simulations, absorption
      processes were assumed to be as rapid as possible, and regional flux (transport
      rate) of inhaled formaldehyde to airway walls was calculated for rats, primates,
      and humans. For uptake of gases like vinyl acetate and acrylic acid vapors,
      physiologically based pharmacokinetic uptake models incorporating anatomical and
      physical information from the CFD models were developed to estimate nasal tissue
      dose in animals and humans. The use of biologically based models in risk
      assessment makes sources of uncertainty explicit and, in doing so, allows
      quantification of uncertainty through sensitivity analyses. Limited resources can
      then be focused on reduction of important sources of uncertainty to make risk
      estimates more accurate.

PMID- 11295866
TI  - Overview of upper respiratory tract vapor uptake studies.
AB  - This review is aimed at highlighting toxicologically relevant physiological and
      biochemical factors that influence the delivery of inhaled vapors to nasal
      tissues. Numerous experiments in rodents have shown that vapor uptake
      efficiencies are dependent on vapor solubility (as measured by blood:air
      partition coefficient) and inspiratory flow rate. Nasal tissues are rich in
      xenobiotic metabolizing enzymes, and it has been shown experimentally through the
      use of metabolic inhibitors that inspired vapors are metabolized in nasal tissue
      and that this process serves to enhance inspired vapor uptake efficiency in that
      site. Metabolism-based species differences in vapor uptake have been observed
      among rodent species. Concentration-dependent changes in vapor uptake have also
      been observed and related to saturation of local metabolic pathways at high
      exposure concentrations. Therefore, appropriate consideration of local metabolism
      is necessary for comprehensive high- to low-dose or species extrapolations of
      nasal toxicity data. Recent studies have provided evidence of sensory nerve
      mediated reflex responses that alter nasal vascular function and may alter nasal
      inspired vapor dosimetric relationships. In toto, these studies also indicate the
      need to define uptake behavior for a vapor of interest over a wide range of
      exposure concentrations due to the possibility of nonlinear metabolism kinetics
      or the induction of nasal reflex and/or toxic responses. Such data are required
      for the formulation of a robust nasal dosimetry model.

PMID- 11295867
TI  - Dosimetry modeling of highly soluble reactive gases in the respiratory tract.

PMID- 11295869
TI  - Mode-of-action-based dosimeters for interspecies extrapolation of vinyl acetate
      inhalation risk.
AB  - Vinyl acetate is used in the manufacture of many polymers. The Clean Air Act
      Amendments of 1990 require that an inhalation risk assessment be conducted to
      assess risks to human health from ambient exposures. Vinyl acetate is a nasal
      carcinogen in rats and induces olfactory degeneration in rats and mice. Because
      of the many unique aspects of the rodent nasal cavity compared to that of humans,
      conventional means for extrapolating dosimetry between species are not
      appropriate. Physiologically based pharmacokinetic (PBPK) and pharmacodynamic
      (PD) modeling can address many of these unique aspects. A PBPK/PD model has been
      developed for vinyl acetate, but the choice of appropriate dosimeter(s) to use
      for interspecies extrapolation depends on a hypothesis regarding mode of action.
      This article summarizes the key studies that formulate a mode of action
      hypothesis for vinyl acetate. Dose-response relationships for vinyl acetate
      induced nonneoplastic and neoplastic responses are highly nonlinear, suggesting
      complex kinetic processes. Carboxylesterase-dependent metabolism of vinyl acetate
      forms acetic acid, a potent cytotoxicant, and acetaldehyde, a weak clastogen.
      Cell death, proposed to be the result of intracellular acidification, results in
      restorative cell proliferation. In conjunction with sufficient genetic damage,
      induced by spontaneous mutation and acetaldehyde-induced DNA-protein cross-links
      (DPX), olfactory degeneration progresses to a state of elevated proliferation and
      eventually, at high vinyl acetate concentrations, to neoplastic transformation.
      Thus, reduction in intracellular pH (pHi) is proposed as the dosimeter most
      closely linked to the earliest stages of vinyl acetate toxicity. Consequently,
      risk assessments that are based on protection of nasal epithelium from
      intracellular acidification will be protective of all subsequent pathological
      responses related to vinyl acetate exposure. Proposing a reasonable mode of
      action is an important step in any risk assessment and is critical to the choice
      of dosimeter(s) to be used for interspecies dosimetry extrapolation.

PMID- 11295868
TI  - A hybrid computational fluid dynamics and physiologically based pharmacokinetic
      model for comparison of predicted tissue concentrations of acrylic acid and other
      vapors in the rat and human nasal cavities following inhalation exposure.
AB  - To assist in interspecies dosimetry comparisons for risk assessment of the nasal
      effects of organic acids, a hybrid computational fluid dynamics (CFD) and
      physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to
      estimate the regional tissue dose of inhaled vapors in the rat and human nasal
      cavity. Application to a specific vapor would involve the incorporation of the
      chemical-specific reactivity, metabolism, partition coefficients, and diffusivity
      (in both air and tissue phases) of the vapor. This report describes the structure
      of the CFD-PBPK model and its application to a representative acidic vapor,
      acrylic acid, for interspecies tissue concentration comparisons to assist in risk
      assessment. By using the results from a series of short-term in vivo studies
      combined with computer modeling, regional nasal tissue dose estimates were
      developed and comparisons of tissue doses between species were conducted. To make
      these comparisons, the assumption was made that the susceptibilities of human and
      rat olfactory epithelium to the cytotoxic effects of organic acids were similar,
      based on similar histological structure and common mode of action considerations.
      Interspecies differences in response were therefore assumed to be driven
      primarily by differences in nasal tissue concentrations that result from regional
      differences in nasal air flow patterns relative to the species-specific
      distribution of olfactory epithelium in the nasal cavity. The results of
      simulations with the seven-compartment CFD-PBPK model suggested that the
      olfactory epithelium of the human nasal cavity would be exposed to tissue
      concentrations of acrylic acid similar to that of the rat nasal cavity when the
      exposure conditions are the same. Similar analysis of CFD data and CFD-PBPK model
      simulations with a simpler one-compartment model of the whole nasal cavities of
      rats and humans provides comparable results to averaging over the compartments of
      the seven-compartment model. These results indicate that the general structure of
      the hybrid CFD-PBPK model applied in this assessment would be useful for target
      tissue dosimetry and interspecies dose comparisons for a wide variety of vapors.
      Because of its flexibility, this CFD-PBPK model is envisioned to be a platform
      for the construction of case-specific inhalation dosimetry models to simulate in
      vivo exposures that do not involve significant histopathological damage to the
      nasal cavity.

PMID- 11295871
TI  - Nasal tissue dosimetry-issues and approaches for "Category 1" gases: a report on
      a meeting held in Research Triangle Park, NC, February 11-12, 1998.
AB  - Three organizations, the Basic Acrylic Monomer Manufacturers (BAMM), Methacrylate
      Producers Association (MPA), and Vinyl Acetate Toxicology Group (VATG), have
      sponsored development of physiologically based pharmacokinetic (PBPK) models for
      nasal tissue dosimetry with, respectively, acrylic acid (AA), methyl methacrylate
      (MMA), and vinyl acetate (VA). These compounds cause lesions in nasal epithelial
      tissues and are classified as "Category 1" gases within the U.S. EPA (1994)
      classification scheme. The National Center for Environmental Assessment in the
      U.S. EPA Office of Research and Development also has continuing interests in
      refining its methods for dosimetry adjustments when data on mode of action are
      available for Category 1 gases. A round-table discussion was held in Research
      Triangle Park, NC, on 11-12 February 1998, to develop a broader appreciation of
      the key processes and parameters required in developing nasal tissue dosimetry
      models. The discussions at the round table drew on these three case studies and
      several background presentations to assess the manner in which chemical-specific
      and mode-of-action data can be incorporated into nasal dosimetry models. The
      round table had representation from the U.S. EPA, academia, and industry. This
      article outlines the presentations and topical areas discussed at the round table
      and notes recommendations made by participants to extend models for nasal
      dosimetry and to develop improved data for modeling. The contributions of several
      disciplines-toxicology, engineering, and physiologically based pharmacokinetic
      (PBPK) modeling-were evident in the discussions. The integration of these
      disciplines in creating opportunities for dosimetry model applications in risk
      assessments has several advantages in the breadth of skills upon which to draw in
      model development. A disadvantage is in the need to provide venues and develop
      cross-discipline dialogue necessary to ensure the understanding of cultural
      attitudes, terminology, and methods. The round-table discussions were fruitful in
      achieving such enhanced understanding and communication. Subsequent elaboration
      of these models will benefit from the interactions of these groups at the round
      table. The round-table discussions have already led to model improvements-as
      noted in several recently published articles. Participants emphasized several
      generic data needs in relation to nasal vapor uptake studies in human subjects,
      to broader discussion of tissue diffusion models, and to extensions to other
      classes of gases. The round-table articles that are published separately in this
      issue and the discussions, captured in this overview, provide a glimpse of the
      state of the science in nasal dosimetry modeling and a clear indication of the
      growth of and continuing opportunities in this important research area.

PMID- 11295870
TI  - Physiologically based clearance/extraction models for compounds metabolized in
      the nose: an example with methyl methacrylate.
AB  - Airstream clearance (with units of volume/time) is the volumetric flow from which
      chemical would have to be completely removed to account for the net loss in the
      nose. Extraction is the proportion of airflow from which the chemical is
      completely removed. Over the past several years we have developed physiologically
      based clearance-extraction (PBCE) models for the nose to assess the
      physiological, biochemical, and anatomical factors that control airstream
      clearance. A generic clearance equation was derived for single airway/tissue
      compartments that had a separate air region and either one, two, or three
      underlying tissue regions. For all of these structures, airstream clearance
      (Cl(sys)) has a common form-Equation (1)-related to tissue clearance (Cltot), gas
      phase diffusional clearance (PAgas), airflow (Q), and the mucus air partition
      coefficient (Hmuc:a). Clsys = CltotHm:aPAgasQ/CltotHm:a(Q + PAgas) + PAgasQ. A
      physiologically based clearance-extraction (PBCE) model for the whole nose
      combined three separate nasal tissue regions, each with a four-compartment tissue
      stack (air, mucus, epithelial tissue, and submucosal region). A steady-state
      solution of the PBCE model successfully described literature results on the
      steady-state extraction of methyl methacrylate (MMA) and several other
      metabolized vapors. Model-derived tissue dosimetry estimates, that is, the amount
      of MMA metabolized in the target epithelial compartment of the olfactory region,
      for rats and humans provide dosimetric adjustment factors (DAFs) required in
      calculating a human reference concentration (RfC) from rodent studies. Depending
      on the assignment of esterase activities to sustentacular and submucosal regions,
      the DAFs from the PBCE model varied between 1.6 and 8.0, compared to the default
      value of 0.145. From the experience with MMA, a minimal data set could be defined
      for building the PBCE model. It consists of mucus:air and blood:air partition
      coefficients, metabolic constants for enzymatic hydrolysis in nasal tissues from
      rat and human tissues, immunohistochemistry of the distribution of these
      activities in rats and human olfactory tissues, and extraction studies in
      anesthetized rats to assess the total nasal metabolism of the test compound.

PMID- 11295872
TI  - Mass transport analysis: inhalation rfc methods framework for interspecies
      dosimetric adjustment.
AB  - In 1994, the U.S. Environmental Protection Agency introduced dosimetry modeling
      into the methods used to derive an inhalation reference concentration (RfC). The
      type of dosimetric adjustment factor (DAF) applied had to span the range of
      physicochemical characteristics of the gases listed on the Clean Air Act
      Amendments in 1991 as hazardous air pollutants (HAPs) and accommodate differences
      in available data with respect to their toxicokinetic properties. A framework was
      proposed that allowed for a hierarchy of dosimetry model structures, from optimal
      to rudimentary, and a category scheme that provided for limiting model structures
      based on physicochemical and toxicokinetic properties. These limiting cases were
      developed from restricting consideration to specific properties relying on an
      understanding of the generalized system based on mass transport theory.
      Physiochemical characteristics included the solubility and reactivity (e.g.,
      propensity to dissociate, oxidize, or serve as a metabolic substrate) of the gas
      and were used as major determinants of absorption. Dosimetric adjustments were
      developed to evaluate portal of entry (POE) effects as well as remote (systemic)
      effects relevant to the toxicokinetic properties of the gas of interest. The gas
      categorization scheme consisted of defining three gas categories: (1) gases that
      are highly soluble and/or reactive, absorbing primarily in the extrathoracic
      airways; (2) gases that are moderately soluble and/or reactive, absorbing
      throughout the airways, as well as accumulating in the bloodstream; and (3) gases
      that have a low water solubility and are lipid soluble such that they are
      primarily absorbed in the pulmonary region and likely to act systemically. This
      article presents the framework and the mass transport theory behind the RfC
      method. Comparison to compartmental approaches and considerations for future
      development are also discussed.

PMID- 11295873
TI  - Dynamic imaging of cerebral blood flow using laser speckle.
AB  - A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is
      presented in this article. By illuminating the cortex with laser light and
      imaging the resulting speckle pattern, relative CBF images with tens of microns
      spatial and millisecond temporal resolution are obtained. The regional CBF
      changes measured with the speckle technique are validated through direct
      comparison with conventional laser-Doppler measurements. Using this method,
      dynamic images of the relative CBF changes during focal cerebral ischemia and
      cortical spreading depression were obtained along with electrophysiologic
      recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique
      yielded high-resolution images of the residual CBF gradient encompassing the
      ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 x 4 mm
      cortical area. Successive speckle images demonstrated a further decrease in
      residual CBF indicating an expansion of the ischemic zone with finely delineated
      borders. Dynamic CBF images during cortical spreading depression revealed a 2 to
      3 mm area of increased CBF (160% to 250%) that propagated with a velocity of 2 to
      3 mm/min. This technique is easy to implement and can be used to monitor the
      spatial and temporal evolution of CBF changes with high resolution in studies of
      cerebral pathophysiology.

PMID- 11295874
TI  - Serial changes in cerebral blood flow and flow-metabolism uncoupling in primates
      with acute thromboembolic stroke.
AB  - The authors recently developed a primate thromboembolic stroke model. To
      characterize the primate model, the authors determined serial changes in cerebral
      blood flow (CBF) and the relation between CBF and cerebral metabolic rate of
      glucose (CMRglc) using high-resolution positron emission tomography.
      Thromboembolic stroke was produced in male cynomolgus monkeys (n = 4). Acute
      obstruction of the left middle cerebral artery was achieved by injecting an
      autologous blood clot into the left internal carotid artery. Cerebral blood flow
      was measured with [15O]H2O before and 1, 2, 4, 6, and 24 hours after
      embolization. CMRglc was measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG)
      24 hours after embolization. Lesion size and location 24 hours after embolization
      was determined by the 2,3,5-triphenyltetrazolium chloride (TTC) staining method.
      The results are summarized as follows: (1) 1 hour after embolization, CBF in the
      temporal cortex and the basal ganglia decreased to < 40% of the contralateral
      values. In these regions, regarded as an ischemic core, CBF decreased further
      with time and CMRglc at 24 hours also decreased. Infarcted lesions as indicated
      by being unstained with TTC were consistently observed in these regions. (2) In
      the parietal cortex and several regions surrounding the ischemic core, CBF was >
      40% of the contralateral values 1 hour after embolization and recovered gradually
      with time (ischemic penumbra). In these regions, CMRglc at 24 hours increased
      compared with that in the contralateral regions, indicating an uncoupling of CBF
      and CMRglc. No obvious TTC-unstained lesions were detected in these regions. The
      authors demonstrated a gradual recovery of reduced CBF, an elevated CMRglc and a
      CBF-CMRglc uncoupling in the penumbra regions of the primate model. Positron
      emission tomography investigations using this model will provide better
      understanding of the pathophysiology of thromboembolic stroke in humans.

PMID- 11295875
TI  - Gender and strain influence on neurogenesis in dentate gyrus of young rats.
AB  - To investigate whether rat hippocampal neurogenesis varies with strain and
      gender, the authors examined proliferating progenitor cells and their progeny in
      young male and female Sprague-Dawley (SD) and spontaneously hypertensive rats
      (SHR) using the thymidine analog bromodeoxyuridine (BrdU) combined with
      immunohistochemistry for the neuronal marker Calbindin D28k and glial fibrillary
      acidic protein. Rats were given 7 consecutive daily BrdU injections and were
      killed 1 day or 4 weeks later to allow for discrimination between proliferation
      and cell survival. Stereologic analysis of the numbers of BrdU-immunoreactive
      cells in the dentate gyrus revealed both a strain difference with significantly
      higher cell proliferation and net neurogenesis in SHR than in SD and a gender
      difference with males from both strains producing significantly more cells than
      their female counterparts. Whereas the number of progenitors four weeks after
      BrdU injections was still significantly greater in male than in female SHRs,
      resulting in a greater net neurogenesis in the male, the number of BrdU
      immunoreactive cells did not differ between male and female SD rats, suggesting a
      greater survival of newly generated cells in the dentate gyrus in female than in
      male SD rats. No sex or strain difference was observed in the relative ratio of
      neurogenesis and gliogenesis.

PMID- 11295876
TI  - Cortical spreading depression induces proinflammatory cytokine gene expression in
      the rat brain.
AB  - Cortical spreading depression (CSD) is characterized by reversible neuronal
      dysfunction in the absence of cell death. Preconditioning by CSD induces
      tolerance against subsequent lethal ischemia. In this study, we used quantitative
      reverse transcriptase-polymerase chain reaction and immunocytochemistry to
      analyze proinflammatory cytokine expression after CSD induced by topical
      application of potassium chloride (KCl) to the cortical surface of rat brains.
      Relative to control cortex, we found an increase of tumor necrosis factor-alpha
      (mean 62-fold, P < 0.001) and interleukin (IL)-1beta (mean 24-fold, P < 0.001)
      mRNA levels within 4 hours ipsilateral to the site of KCl application. At 16
      hours cytokine expression was decreasing toward baseline levels. Ipsilateral
      cytokine induction was abolished by pretreatment with the noncompetitive N-methyl
      d-aspartate antagonist, MK-801. In contrast to focal cortical infarction,
      cytokine induction in CSD was not accompanied by the expression of inducible
      nitric oxide synthase mRNA. In immunocytochemical studies, expression of IL-1beta
      protein was localized to ramified microglia in cortical layers I to III of the
      ipsilateral hemisphere. Our finding that NMDA receptor signaling without
      subsequent neuronal cell death is sufficient to induce inflammatory cytokine
      expression in the brain has basic implications for central nervous system
      immunoregulation. We postulate that cytokine expression in CSD forms part of a
      physiologic stress response that contributes to the development of ischemic
      tolerance in this and other preconditioning paradigms.

PMID- 11295877
TI  - Cell permeable exogenous ceramide reduces infarct size in spontaneously
      hypertensive rats supporting in vitro studies that have implicated ceramide in
      induction of tolerance to ischemia.
AB  - Previous work in primary cell culture has shown that TNF-alpha and ceramide are
      involved in the signaling that induces tolerance to brain ischemia (Ginis et al.,
      1999; Liu et al., 2000). To validate the in vitro studies, the authors
      administered cell permeable analogs of ceramides intracisternally or
      intravenously to examine their effect on neuroprotection after focal cerebral
      ischemia. Permanent middle cerebral artery occlusion (MCAO) was performed in
      spontaneously hypertensive rats. Infarct volumes were assessed at 24 hours after
      surgery. D-erythro-N-acetylsphingosine (C2-ceramide) or its vehicle was infused
      intracisternally for 1 hour before MCAO. In a second set of studies, D-erythro-N
      octanoylsphingosine (C8-ceramide) or its vehicle was injected intravenously 48 or
      24 hours before MCAO to mimic preconditioning (PC) and was also injected 5
      minutes after MCAO. C2-ceramide infusion significantly reduced infarct volumes by
      approximately 14% (P < 0.05). C8-ceramide injection reduced infarct volumes
      approximately 17% compared with controls. This effect was constant and
      significant compared with controls over the time periods examined (P < 0.01).
      This work supports findings in primary brain cell cultures that implicate
      ceramide as a downstream signal that is proximate to development of tolerance to
      brain ischemia. Because the degree of protection represents approximately 50% of
      the maximal infarct reduction observed in this model, there are probably
      additional signaling pathways that subserve tolerance.

PMID- 11295878
TI  - bcl-2 Antisense treatment prevents induction of tolerance to focal ischemia in
      the rat brain.
AB  - In the rat, 60 minutes of transient ischemia to the middle cerebral artery
      results in infarction of the caudate putamen. Ischemic preconditioning with 20
      minutes of transient focal ischemia produced tolerance (attenuated infarction
      volume) to 60 minutes of subsequent focal ischemia administered three days, five
      days, or seven days later. Western blots from tolerant caudate putamen
      demonstrated increased bcl-2 expression, maximum at 3 days and persisting through
      7 days. Immunocytochemical examination found that bcl-2 was expressed in cells
      with both neuronal and nonneuronal morphology in striatum after preconditioning
      ischemia. bcl-2 antisense oligodeoxynucleotides (ODNs), bcl-2 sense ODNs, or
      artificial cerebrospinal fluid (CSF, vehicle) was infused into the lateral
      ventricle for the 72 hours between the 20-minute ischemic preconditioning and the
      60-minute period of ischemia. Antisense ODN treatment reduced expression of bcl-2
      in the striatum and blocked the induction of tolerance by preconditioning
      ischemia. Sense and CSF treatments had no effect on either bcl-2 expression or
      tolerance. In this model of induced tolerance to focal ischemia, bcl-2 appears to
      be a major determinant.

PMID- 11295879
TI  - Brain vessels normally undergo cyclic activation and inactivation: evidence from
      tumor necrosis factor-alpha, heme oxygenase-1, and manganese superoxide dismutase
      immunostaining of vessels and perivascular brain cells.
AB  - Studies of vascular biology during the past decade have identified an expanding
      list of agonists and antagonists that regulate local hemostasis, inflammation,
      and reactivity in blood vessels. Interactions at the blood-endothelial interface
      are intricate and complex and have been postulated to play a role in the
      initiation of stroke and the progression of brain injury during early hours of
      ischemia, particularly in conjunction with reperfusion injury (Hallenbeck, 1996).
      In the current study of normal and activated vessels in rat brain, immunoreactive
      tumor necrosis factor-alpha (TNF-alpha), heme oxygenase-1 (HO-1), and manganese
      superoxide dismutase (MnSOD) exhibit concentric perivascular rings involving
      vessel wall and surrounding parenchyma that appear to coincide with one another
      in serial sections. The ring patterns suggest periodic radial expansion of these
      molecules released through a process of cyclic activation and inactivation of
      brain vessel segments. In this process, the rings appear randomly scattered
      instead of affecting all vessels within a high power field (HPF) synchronously.
      The average number of vessels per HPF (mean +/- SD) with perivascular cuffs of
      immunoreactive MnSOD increased from 51 +/- 28 in Wistar, 72 +/- 46 in Wistar
      Kyoto, and 84 +/- 30 in Sprague Dawley rats (no spontaneous strokes) to 184 +/-
      72 in spontaneously hypertensive stroke-prone rats (spontaneous strokes).
      Perivascular immunoreactive cuffs are also increased in spontaneously
      hypertensive rats by induction of cytokine expression by lipopolysaccharide (64
      +/- 15 vs. 131 +/- 32 /HPF). The patterns of TNF-alpha, HO-1, and MnSOD in naive
      animals are interpreted to indicate that focal hemostatic balance normally
      fluctuates in brain vessels and influences surrounding parenchymal cells.
      Perivascular immunoreactive cuffs representing this process are more frequent in
      animals with lipopolysaccharide-induced endothelial activation or genetic stroke
      proneness.

PMID- 11295880
TI  - Peroxynitrite reduces vasodilatory responses to reduced intravascular pressure,
      calcitonin gene-related peptide, and cromakalim in isolated middle cerebral
      arteries.
AB  - Vasodilatory responses to progressive reductions in intravascular pressure or to
      calcitonin gene-related peptide (CGRP) or cromakalim were determined in rodent
      middle cerebral arteries (MCAs) before and after treatment with peroxynitrite
      (ONOO-). Middle cerebral artery diameters in isolated, pressurized MCAs were
      measured as intravascular pressure was reduced from 100 to 20 mm Hg in 20-mm Hg
      increments before and after inactive ONOO-, pH-adjusted ONOO-, or 10, 20, or 40
      micromol/L ONOO- was added to the bath. In other MCAs, responses to CGRP (1 x 10
      9 - 5 x 10-8) or cromakalim (3 x 10-8 - 8 x 10-7) were measured before and after
      the addition of 25 micromol/L ONOO-. Inactive ONOO- (n = 6, P = 0.40), pH
      adjusted ONOO- (n = 6, P = 0.29), and 10 micromol/L ONOO- (n = 6, P = 0.88) did
      not reduce vasodilatory responses to reduced intravascular pressure. Middle
      cerebral arteries treated with 20 (n = 6, P < 0.0001) and 40 (n = 6, P > 0.0001)
      micromol/L ONOO- constricted significantly when intravascular pressure was
      reduced. Vasodilatory responses to CGRP or cromakalim were reduced by ONOO- (P >
      0.02, n = 6 and P > 0.01, n = 7, respectively). ONOO- had no effect on
      vasoconstriction in response to serotonin or vasodilation in response to KCl.
      These studies demonstrate that ONOO- reduces multiple cerebral vasodilatory
      responses.

PMID- 11295881
TI  - The metabotropic glutamate receptor system protects against ischemic free radical
      programmed cell death in rat brain endothelial cells.
AB  - As one of the key determinants of ischemic injury, cerebrovascular endothelial
      cell (EC) degeneration may be dependent upon the generation of the free radical
      nitric oxide (NO) and the subsequent induction of programmed cell death (PCD).
      Although the mechanisms that can prevent EC injury are most likely multifactorial
      in origin, the metabotropic glutamate receptor (mGluR) system may represent a
      novel therapeutic approach for ECs given the ability of the mGluR system to
      reverse neuronal cell injury. This study examined the modulation of individual
      subtypes of mGluRs during anoxia and NO toxicity in primary rat cerebrovascular
      ECs. Cell injury was determined through trypan blue dye exclusion, intracellular
      lactate dehydrogenase release, DNA fragmentation, membrane phosphatidylserine
      (PS) exposure, and cysteine protease activity. Anoxia, through the generation of
      NO, and exposure to exogenous NO were directly toxic to ECs. Exposure to NO
      rapidly decreased EC viability from 98% +/- 2% to 40% +/- 9%, increased DNA
      fragmentation from 2% +/- 2% to 61% +/- 9%, and increased membrane PS exposure
      from 3% +/- 3% to 66% +/- 6% over a 24-hour period. Activation of the mGluR
      system significantly increased EC survival through the prevention of NO-induced
      DNA fragmentation and cellular membrane PS residue exposure. In contrast,
      antagonism of the mGluR system failed to prevent PCD. Cytoprotection by the mGluR
      system was dependent, at least in part, upon the direct inhibition of NO
      generated caspase 1- and caspase 3-like activities. Further investigation into
      the ability of the mGluR system to prevent PCD in ECs may open new therapeutic
      avenues for the treatment of cerebrovascular injury.

PMID- 11295882
TI  - Variability of blood-brain ratios of phenylalanine in typical patients with
      phenylketonuria.
AB  - Blood-brain ratios (BBR) of phenylalanine (Phe) were determined by quantitative
      in vivo 1H magnetic resonance spectroscopy (1H-MRS) in 17 adult patients with
      early-treated phenylketonuria who were randomly selected from a sample of 75
      adults. Measurements were performed in all patients during steady-state
      conditions. The BBR showed a unimodal distribution with a mean of 4.0 (range 3.3
      to 4.5). Blood-brain ratios were comparable for subgroups of patients with
      genotypes classified as severe, moderate, or mild and for patients on different
      types of diets. Brain Phe concentrations showed a strong linear correlation with
      blood Phe values (r = 0.93, P < 0.001). There were no saturation effects for
      blood Phe values up to 1.8 mmol/L, and a local regression analysis did not
      confirm increasing BBR for increasing blood Phe values. The intellectual outcome
      (Wechsler Adult Intelligence Scale) was correlated with long-term dietary control
      (r = -0.65, P < 0.05), fluctuation of blood Phe values during treatment (r = 
      0.60, P < 0.05), and concurrent blood and brain Phe concentration. The severity
      of white matter changes visible on magnetic resonance images (MRI) was increased
      with high blood and brain Phe concentrations but failed to reach statistical
      significance. No correlation was found between BBR values, intelligence quotient,
      and MRI grade. Based on the assumption that BBR show intraindividual stability,
      the current data do not support the hypothesis that blood-brain barrier transport
      of Phe is a key explanatory factor for outcome variability in the vast majority
      of "typical" patients with phenylketonuria.

PMID- 11295883
TI  - Cerebrovascular adaptation in chronic hydrocephalus.
AB  - This study characterizes the regional changes in vascularity, which accompanies
      chronic progressive hydrocephalus. Fifteen dogs underwent surgical induction of
      hydrocephalus and were used for histologic studies. Animals were divided into 4
      groups: surgical control, short term (< or = 5 weeks), intermediate term (8
      weeks), and long term (10 to 12 weeks). Vessel diameter, density, and luminal
      area were calculated by imaging quantification after manual vessel identification
      in the cortical gray, white matter, and caudate nucleus. Capillary vessel
      diameter decreased 23.5% to 30.2% (P < 0.01) in the caudate, but then returned to
      normal at 12 weeks. Capillary vessel density decreased 53.5% (P < 0.05) in the
      cortical gray, but then increased to 234.8% (P < 0.01) over surgical controls at
      12 weeks. There was no initial decrease in capillary density in the caudate;
      however, the long-term group capillary density was significantly greater (172.8%
      to 210.5%, P < 0.01) than surgical controls. Overall, there was a short-term
      decrease in lumen area, with recovery in the longer term. Glial fibrillary acidic
      protein (GFAP) immunohistochemistry demonstrated the pattern of GFAP staining and
      reactive astrocytes differed in the caudate compared with the occipital cortex.
      This data suggest that an increase in capillary density and diameter may be an
      adaptive process allowing maintenance of adequate cerebral perfusion and
      metabolic support in the hypoxic environment of chronic hydrocephalus.

PMID- 11295884
TI  - Positron emission tomographic measurement of brain acetylcholinesterase activity
      using N-[(11)C]methylpiperidin-4-yl acetate without arterial blood sampling:
      methodology of shape analysis and its diagnostic power for Alzheimer's disease.
AB  - N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) is a radiotracer that has been
      used successfully for the quantitative measurement of acetylcholinesterase (AChE)
      activity in the human brain with positron emission tomography (PET) using a
      standard compartment model analysis and a metabolite-corrected arterial input
      function. In the current study, the authors evaluated the applicability of a
      simple kinetic analysis without blood sampling, namely shape analysis. First, the
      authors used computer simulations to analyze factors that affect the precision
      and bias of shape analysis, then optimized the shape analysis procedure for
      [11C]MP4A. Before shape analysis execution, the later part of dynamic PET data
      except for the initial 3 minutes were smoothed by fitting to a bi-exponential
      function followed by linear interpolation of 8 data points between each of
      adjacent scan frames. Simulations showed that shape analysis yielded estimates of
      regional metabolic rates of [11C]MP4A by AChE (k3) with acceptable precision and
      bias in brain regions with low k3 values such as neocortex. Estimates in regions
      with higher k3 values became progressively more inaccurate. The authors then
      applied the method to [11C]MP4A PET data in 10 healthy subjects and 20 patients
      with Alzheimer's disease (AD). There was a highly significant linear correlation
      in regional k3 estimates between shape and compartment analyses (300 neocortical
      regions, [shape k3] = 0.93 x [NLS k3], r = 0.89, P < 0.001). Significant
      reductions in k3 estimates of frontal, temporal, parietal, occipital, and
      sensorimotor cerebral cortices in patients with AD as compared with controls were
      observed when using shape analysis (P < 0.013, two-tailed t-test), although these
      reductions (17% to 20%) were somewhat less than those obtained by compartment
      analysis (22% to 27%). The sensitivity of shape analysis for detecting
      neocortical regions with abnormally low k3 in the 20 patients with AD (92 out of
      200 regions, 46%) also was somewhat less than compartment analysis (136 out of
      200 regions, 68%). However, taking its simplicity and noninvasiveness into
      account, the authors conclude that quantitative measurement of neocortical AChE
      activity with shape analysis and [11C]MP4A PET is practical and useful for
      clinical diagnosis of AD.

PMID- 11295885
TI  - A strategy for removing the bias in the graphical analysis method.
AB  - The graphical analysis method, which transforms multiple time measurements of
      plasma and tissue uptake data into a linear plot, is a useful tool for rapidly
      obtaining information about the binding of radioligands used in PET studies. The
      strength of the method is that it does not require a particular model structure.
      However, a bias is introduced in the case of noisy data resulting in the
      underestimation of the distribution volume (DV), the slope obtained from the
      graphical method. To remove the bias, a modification of the method developed by
      Feng et al. (1993), the generalized linear least squares (GLLS) method, which
      provides unbiased estimates for compartment models was used. The one compartment
      GLLS method has a relatively simple form, which was used to estimate the DV
      directly and as a smoothing technique for more general classes of model
      structures. In the latter case, the GLLS method was applied to the data in two
      parts, that is, one set of parameters was determined for times 0 to T1 and a
      second set from T1 to the end time. The curve generated from these two sets of
      parameters then was used as input to the graphical method. This has been tested
      using simulations of data similar to that of the PET ligand [11C]-d-threo
      methylphenidate (MP, DV = 35 mL/mL) and 11C raclopride (RAC, DV = 1.92 mL/mL) and
      compared with two examples from image data with the same tracers. The noise model
      was based on counting statistics through the half-life of the isotope and the
      scanning time. Five hundred data sets at each noise level were analyzed. Results
      (DV) for the graphical analysis (DV(G)), the nonlinear least squares (NLS) method
      (DV(NLS)), the one-tissue compartment GLLS method (DV(F)), and the two part GLLS
      followed by graphical analysis (DV(FG)) were compared. DV(FG) was found to
      increase somewhat with increasing noise and in some data sets at high noise
      levels no estimate could be obtained. However, at intermediate levels it provided
      a good estimation of the true DV. This method was extended to use a reference
      tissue in place of the input function to generate the distribution volume ratio
      (DVR) to the reference region. A linearized form of the simplified reference
      tissue method of Lammertsma and Hume (1996) was used. The DVR generated directly
      from the model (DVR(FL)) was compared with DVR(FG) (determined from a "smoothed"
      uptake curve as for DV(FG)) using the graphical method.

PMID- 11295887
TI  - Multifidus EMG and tension-relaxation recovery after prolonged static lumbar
      flexion.
AB  - STUDY DESIGN: The electromyogram (EMG) from the in vivo feline L1 to the L7
      multifidus was recorded during the application of a 20-minute static lumbar
      flexion and after 7 hours of rest. OBJECTIVE: To determine the recovery of
      tension-relaxation and laxity in the lumbar viscoelastic structures as well as
      the recovery of reflexive EMG activity in the multifidus after prolonged static
      flexion. SUMMARY OF BACKGROUND: It has been established that prolonged static
      flexion of the spine induces creep or tension-relaxation in its viscoelastic
      structures as well as a sharp decrease in the reflexive activity of the dorsal
      musculature and initiation of spasms. Epidemiologic studies have pointed out that
      such static flexion is associated with unusually high rates of low back
      disorders. The rate and pattern of recovery of reflexive muscular activity with
      rest after static flexion is still unknown. METHODS: The lumbar spines of seven
      in vivo feline preparations were subjected to 20 minutes of passive anterior
      flexion followed by 7 hours of rest while monitoring flexion tension, EMG from
      the L1-L7 multifidus muscles, and the strain of the L4/L5 supraspinal ligament. A
      model describing the pattern of recovery of muscular activity and viscoelastic
      tension was developed. RESULTS: Twenty minutes of lumbar flexion was associated
      with an initial sharp decrease of multifidus EMG activity followed by spasms.
      During rest, EMG activity demonstrated an initial hyperexcitability on flexion,
      followed by an exponential recovery of muscle activity. Full recovery of residual
      strain in the L4/L5 supraspinous ligament and multifidus activity was not
      obtained after 7 hours of rest. CONCLUSIONS: Static flexion of the lumbar spine
      is an extremely imposing function on its viscoelastic tissues, resulting in
      spasms and requiring long periods of rest before normal functions are re
      established.

PMID- 11295888
TI  - Impaired postural control of the lumbar spine is associated with delayed muscle
      response times in patients with chronic idiopathic low back pain.
AB  - STUDY DESIGN: Balance performance in unstable sitting and trunk muscle response
      to quick force release were measured in 16 patients with chronic low back pain
      and 14 matched healthy control subjects. OBJECTIVES: To determine whether
      patients with low back pain will exhibit poorer postural control, which will be
      associated with longer average muscle response times. SUMMARY OF BACKGROUND DATA:
      Larger postural sway during standing and delayed trunk muscle response times for
      patients with low back pain have been reported in several independent studies.
      METHODS: Unstable sitting test was accomplished by attaching different sized
      hemispheres to the bottom of a seat. Subjects performed trials with eyes open and
      closed while the displacements of the center of pressure were measured with a
      force plate underneath the seat. Response to a quick force release was recorded
      from 12 major trunk muscles with surface electromyography. Subjects performed
      isometric trunk exertions in a semi-seated position when the resisted force was
      suddenly released with an electromagnet. Average muscle response times and
      balance performance were correlated using a linear regression analysis. RESULTS:
      Patients with low back pain demonstrated poorer balance performance than healthy
      control volunteers, especially at the most difficult levels. Patients also had
      delayed muscle response times to quick force release. Average muscle onset times
      together with age and weight correlated significantly with balance performance
      with closed eyes (R(2) = 0.46), but not with eyes opened (R(2) = 0.18).
      CONCLUSIONS: Patients with chronic low back pain demonstrated poorer postural
      control of the lumbar spine and longer trunk muscle response times than healthy
      control volunteers. Correlation between these two phenomena suggests a common
      underlying pathology in the lumbar spine.

PMID- 11295889
TI  - Lifting strategy and stability in strength-impaired elders.
AB  - STUDY DESIGN: Ninety-six subjects underwent biomechanical analysis of freestyle
      box lifting. OBJECTIVES: To relate lifting strategy to lower extremity muscle
      strength and postural stability in functionally limited elders. SUMMARY OF
      BACKGROUND DATA: Back pain and postural instability in elders is rampant and
      poorly understood. Much of the literature on lifting relates to young subjects.
      METHODS: Lifting strategy for 91 functionally limited elders was classified by
      timing of peak power in the back and knee joints. Isometric hip and knee extensor
      strength and postural stability were compared among strategy classifications.
      Postural stability was analyzed by measuring center of gravity (CG) displacement
      during lifting. RESULTS: Three lift strategy groups were established: back-lift,
      or back dominant strategy (BDS); leg-lift, or leg dominant strategy (LDS); and
      leg-dominant back-first mixed strategy (LDB). Subjects with relatively strong hip
      and knee extensors used leg dominant strategy; subjects with relatively strong
      knee, but weak hip, extensors used leg-dominant back-first mixed strategy; and
      subjects with weak hip and knee extensors used back dominant strategy. Leg
      dominant strategy and leg-dominant back-first mixed strategy engendered less
      center of gravity displacement and thus were posturally more stable than the back
      dominant strategy. CONCLUSION: Subjects apparently chose their lift strategy
      based on their hip and knee extensor strength. Weaker elders using a less stable
      back dominant strategy could be susceptible to falls and subsequent long bone and
      vertebral body fractures. Clinicians could identify at-risk elders by muscle
      testing. Beyond emphasizing strength and endurance exercise in elderly patients,
      weak elders should be taught to use a leg dominant lifting strategy, or if they
      are not physically able, to use a combined back/leg strategy.

PMID- 11295891
TI  - Outcomes of posterolateral lumbar fusion in Utah patients receiving workers'
      compensation: a retrospective cohort study.
AB  - STUDY DESIGN: A retrospective cohort study consisting of a medical record review
      and a follow-up telephone survey of patients with lumbar fusion, at least 2 years
      after their surgery, was performed. OBJECTIVE: To identify presurgical correlates
      and long-term outcomes from posterolateral lumbar fusion in Utah patients
      receiving workers' compensation. SUMMARY OF BACKGROUND DATA: Lumbar fusion has
      been criticized for its highly variable outcomes, and compensated workers are at
      particular risk for poor outcomes. Evidence suggests that presurgical
      psychosocial factors may be important modifiers of back pain reporting and back
      surgery outcomes. METHODS: The patients in this study were 185 compensated
      workers in Utah who underwent posterolateral lumbar fusion. Patient medical
      records were independently reviewed, and medical and sociodemographic variables
      were coded. A telephone outcome survey was completed with 130 patients (70%) an
      average of 4.6 years after their surgery. RESULTS: Reported solid fusion,
      reoperation, and disability rates for the follow-up sample were 74%, 24%, and
      25%, respectively. As reported by the patients, 41% experienced no change or a
      worsened quality of life. Mean scores from the Roland and Morris Back Pain
      Disability Questionnaire, the Stauffer-Coventry-Index, and the Short-Form 20
      Multidimensional Health Survey indicate that many patients experienced
      postsurgical dysfunction. Presurgical predictors of outcomes were number of prior
      low back operations, income at time of injury, age, litigation, and depression.
      CONCLUSIONS: Outcomes of posterolateral lumbar fusion among compensated workers
      in Utah are inconsistent. Outcomes can be predicted by presurgical
      sociodemographic variables. Screening for such presurgical risk factors may be
      important for prudent surgical decisions and rehabilitation planning.

PMID- 11295893
TI  - Spontaneous postoperative cerebrospinal fluid leaks following application of anti
      adhesion barrier gel: case report and review of the literature.
AB  - STUDY DESIGN: This report documents cerebrospinal fluid leakage after application
      of anti-adhesion barrier gel in a single-surgeon clinical series of 27 patients
      treated with ADCON-L (Gliatech, Cleveland, OH) during surgery. OBJECTIVE: To
      discuss a heretofore unreported postoperative complication when using an anti
      adhesion barrier gel for lumbar spinal surgery. SUMMARY OF BACKGROUND DATA: Anti
      adhesion barrier gel has been touted as a beneficial adjunct to lumbar surgery.
      No previous report has been identified that documents the complication
      encountered in this series. METHODS: During the time that ADCON-L was used, in a
      9-month period, all spinal surgeries were reviewed, and those cases where ADCON-L
      was used were documented. The reports of all surgeries then were reviewed for
      complications during surgery, and clinical follow-up information was obtained.
      RESULTS: Five of 27 cases receiving ADCON-L during surgery developed
      cerebrospinal fluid leakage. Three of these patients required reoperation.
      CONCLUSION: The excessive rate of cerebrospinal fluid leakage after the use of
      ADCON-L is significant, and the morbidity associated with its use outweighs the
      potential benefit of the product.

PMID- 11295895
TI  - One-stage posterior hemivertebra resection and correction using segmental
      posterior instrumentation.
AB  - STUDY DESIGN: A retrospective study of 12 patients with congenital kyphoscoliosis
      caused by a single hemivertebra who underwent one-stage posterior hemivertebra
      resection and correction by posterior segmental instrumentation. OBJECTIVES: To
      evaluate the surgical outcomes of 12 patients with hemivertebra treated by
      hemivertebra resection by single posterior approach and correction with segmental
      posterior instrumentation. SUMMARY OF BACKGROUND DATA: Congenital scoliosis
      caused by hemivertebra causes extremely severe curves in some patients. Posterior
      fusion or posterior and anterior hemi-epiphysiodesis is performed to prevent
      progression of the deformity. The results of these procedures have been variable
      and not promising, especially in an adolescent patient with fixed kyphoscoliotic
      deformity. Hemivertebra resection offers more certain results and better
      correction of the deformity. To date, hemivertebra resection is performed by
      anterior and posterior approaches either by one-stage or two-stage operation. Few
      reports have been published describing a procedure consisting of one-stage
      posterior hemivertebra resection and correction of the deformity by segmental
      posterior instrumentation. METHODS: A total of 12 patients with a single
      hemivertebra between the ages 8-24 years who underwent operative treatment were
      evaluated for a minimum of 2 years. All patients had a single nonincarcerated
      hemivertebra [T9 (1 patient), T10 (2), T11 (2), T12 (4), and L1 (3)]. After
      posterior hemivertebra resection, segmental posterior instrumentation was used
      for correction of the kyphoscoliotic deformity [CD (4 patients), Kaneda SR (2),
      and ISOLA (6)]. Radiographic evaluations were conducted on the preoperative,
      postoperative, and follow-up standing posteroanterior and lateral radiographs.
      RESULTS: All 12 patients had kyphoscoliotic deformity. Preoperative scoliosis
      averaging 49 degrees was corrected to 18 degrees (correction rate, 64%).
      Preoperative kyphosis of 40 degrees was corrected to 17 degrees of kyphosis.
      Trunk shift of 23 mm was improved to 3 mm. Correction loss was 2 degrees in the
      frontal plane and 3 degrees in the sagittal plane, and no patients showed more
      than 5 degrees of correction loss. No intraoperative complications were noted.
      Solid fusion was obtained in all patients, and no implant failure was verified at
      the final radiographic evaluations. CONCLUSIONS: This study indicated that
      correction of kyphoscoliosis caused by a single hemivertebra can be effectively
      conducted by one-stage posterior hemivertebra resection and correction using
      segmental posterior instrumentation. The operation was safe, and no associated
      adverse complications were noted. This procedure is best indicated for adolescent
      patients with a structural kyphoscoliotic deformity caused by a thoracic or
      thoracolumbar single hemivertebra.

PMID- 11295896
TI  - Centralization phenomenon as a prognostic factor for chronic low back pain and
      disability.
AB  - STUDY DESIGN: Two hundred twenty-three consecutive adults with acute low back
      pain with or without referred spinal symptoms were treated conservatively and
      followed prospectively for 1 year. OBJECTIVES: To investigate the predictive
      value of centralization phenomenon (CP) with psychosocial variables previously
      identified as important risk factors for patients with acute onset of nonserious
      or nonspecific low back pain who subsequently develop chronic pain or disability.
      SUMMARY OF BACKGROUND DATA: Psychosocial factors have been shown to be predictors
      of chronic disability, but measures from physical examination rarely predict
      chronic behavior. The authors of the present study investigated whether dynamic
      assessment of changes in clinical measures during treatment could be used to
      classify patients and predict occurrence of chronic pain or disability. METHODS:
      Patients with acute symptoms and no history of surgery were treated by five
      physical therapists trained in McKenzie evaluation/treatment methods. Seventy
      three percent were receiving workers' compensation benefits. At initial
      evaluation and discharge, 23 independent variables were assessed representing
      psychosocial, clinical, and demographic factors. Pain location changes to
      repeated trunk movements were assessed at every visit. Patients were placed in
      two groups: 1) those with pain that did not centralize and 2) those who
      completely centralized or demonstrated partial reduction of pain location with
      time. Treatment was individualized and based on McKenzie methods. Patients were
      contacted at 12 months after discharge, and dependent variables of pain
      intensity, return to work status, sick leave at work, activity interference at
      home, and continued use of health care were assessed. RESULTS: Nine independent
      variables influenced pain symptoms or disability. Pain pattern classification
      (noncentralization) and leg pain at intake were the strongest predictive
      variables of chronicity. CONCLUSION: Dynamic assessment of change in anatomic
      pain location during treatment and leg pain at intake were predictors of
      developing chronic pain and disability.

PMID- 11295898
TI  - A comparison of symptom checklist 90-revised profiles from patients with chronic
      pain from whiplash and patients with other musculoskeletal injuries.
AB  - STUDY DESIGN: A quasi-experimental design was used to compare the Symptom
      Checklist 90-Revised profiles (SCL-90-R) from a group of patients with whiplash
      injuries (n = 67) and a group with mixed musculoskeletal pain (n = 91).
      OBJECTIVES: To test the discriminant validity of the characteristic SCL-90-R
      whiplash profile as proposed by Wallis and Bogduk using a multivariate
      statistical technique. SUMMARY OF BACKGROUND DATA: On the basis of two studies by
      themselves and their colleagues, Wallis and Bogduk proposed a characteristic SCL
      90-R profile evident in samples of patients with whiplash injuries. Their
      assertion has not been tested empirically in any published studies. METHODS: The
      participants in this study consisted of 158 patients at a rehabilitation hospital
      who completed the SCL-90-R under standard instructions and subsequently were
      diagnosed by a team comprising a chiropractor, physical therapist, and physician.
      The participants were categorized as having whiplash-associated disorders or pain
      caused by other musculoskeletal injuries. A profile analysis following
      Hotelling's method was used to determine the comparability of SCL-90-R profiles
      from the two groups. RESULTS: The profile analysis showed no statistically
      significant differences between the groups with regard to either the shape or the
      overall elevation of their psychological profiles. The SCL-90-R profiles from
      both groups were similar to those reported from other chronic pain syndromes,
      with elevations on the Somatization, Depression, Obsessive-Compulsive, and
      Psychoticism scales. CONCLUSIONS: The current study failed to support the
      validity of a distinctive SCL-90-R profile for patients with whiplash injuries.
      Instead, the results suggest that the psychological consequences of experiencing
      chronic pain from whiplash-associated disorders are similar to the psychological
      consequences of chronic pain from other musculoskeletal injuries.

PMID- 11295899
TI  - Reliability of the isokinetic trunk extensor test, Biering-Sorensen test, and
      Astrand bicycle test: assessment of intraclass correlation coefficient and
      critical difference in patients with chronic low back pain and healthy
      individuals.
AB  - STUDY DESIGN: A reliability study was performed. OBJECTIVE: To determine the
      intersession reproducibility of the isokinetic trunk extensor strength test, the
      Biering-Sorensen test, and the Astrand test by calculation of the intraclass
      correlation coefficient and the critical difference. SUMMARY OF BACKGROUND DATA:
      Several physical measurements have been used in clinical evaluation of patients
      with chronic low back pain. Reliability can be evaluated by calculation of either
      intraclass correlation coefficient or critical difference, but interpretation of
      the results may vary depending on which method is used. METHODS: For this study,
      31 patients with chronic low back pain carried out the isokinetic trunk extensor
      test, the Biering-Sorensen test, and the Astrand test as also did age- and gender
      matched healthy individuals. Measurements were performed in three separate
      sessions at the same time of the day and by the same experienced examiner. The
      intervals between the sessions were 5 to 10 days. RESULTS: The isokinetic tests
      showed a learning effect between Tests 1 and 2. For the isokinetic test, the
      critical difference increased with increased angular velocities from 28% to 63%
      in the patients and from 27% to 39% in the healthy subjects. The critical
      differences for the patients and the healthy individuals were 57% vs 54% for the
      Biering-Sorensen test and 21% vs 23% for the Astrand test, respectively. The
      intraclass correlation coefficient ranged from 93% to 98% in the patients and 80%
      98% in the healthy individuals. CONCLUSIONS: The reliability was found to be
      acceptable for the Astrand test and the isokinetic test at 60 degrees per second,
      as evaluated by the critical difference. All the tests were highly reliable
      according to the intraclass correlation coefficient, except for Biering-Sorensen
      test for healthy individuals. The critical difference is the preferable measure
      because calculation of the intraclass correlation coefficient may give a
      misleading high estimate of reliability.

PMID- 11295900
TI  - Preventive interventions for back and neck pain problems: what is the evidence?
AB  - STUDY DESIGN: A review of controlled trials. OBJECTIVES: To determine which
      interventions are used to prevent back and neck pain problems as well as what the
      evidence is for their utility. SUMMARY OF BACKGROUND DATA: Given the difficulty
      in successfully treating long-term back and neck pain problems, there has been a
      call for preventive interventions. Little is known, however, about the value of
      preventive efforts for nonpatients, e.g., in the general population or workplace.
      METHODS: The literature was systematically searched to locate all investigations
      that were: 1) specifically designed as a preventive intervention; 2) randomized
      or nonrandomized controlled trials; and, 3) using subjects not seeking treatment.
      Outcome was evaluated on the key variables of reported pain, report of injury,
      dysfunction, time off work, health-care utilization, and cost. Conclusions were
      drawn using a grading system. RESULTS: Twenty-seven investigations meeting the
      criteria were found for educational efforts, lumbar supports, exercises,
      ergonomics, and risk factor modification. For back schools, only one of the nine
      randomized trials reported a significant effect, and there was strong evidence
      that back schools are not effective in prevention. Because the randomized trials
      concerning lumbar supports were consistently negative, there is strong evidence
      that they are not effective in prevention. Exercises, conversely, showed stable
      positive results in randomized controlled trials, giving consistent evidence of
      relatively moderate utility in prevention. Because no properly controlled trials
      were found for ergonomic interventions or risk factor modification, there was not
      good quality evidence available to draw a conclusion. CONCLUSIONS: The results
      concerning prevention for subjects not seeking medical care are sobering. Only
      exercises provided sufficient evidence to conclude that they are an effective
      preventive intervention. There is a dire lack of controlled trials examining
      broad-based multidimensional programs. The need for high quality outcome studies
      is underscored.

PMID- 11295901
TI  - A randomized clinical trial of exercise and spinal manipulation for patients with
      chronic neck pain.
AB  - STUDY DESIGN: A randomized, parallel-group, single-blinded clinical trial was
      performed. After a 1-week baseline period, patients were randomized to 11 weeks
      of therapy, with posttreatment follow-up assessment 3, 6, and 12 months later.
      OBJECTIVES: To compare the relative efficacy of rehabilitative neck exercise and
      spinal manipulation for the management of patients with chronic neck pain.
      SUMMARY OF BACKGROUND DATA: Mechanical neck pain is a common condition associated
      with substantial morbidity and cost. Relatively little is known about the
      efficacy of spinal manipulation and exercise for chronic neck pain. Also, the
      combination of both therapies has yet to be explored. METHODS: Altogether, 191
      patients with chronic mechanical neck pain were randomized to receive 20 sessions
      of spinal manipulation combined with rehabilitative neck exercise (spinal
      manipulation with exercise), MedX rehabilitative neck exercise, or spinal
      manipulation alone. The main outcome measures were patient-rated neck pain, neck
      disability, functional health status (as measured by Short Form-36 [SF-36]),
      global improvement, satisfaction with care, and medication use. Range of motion,
      muscle strength, and muscle endurance were assessed by examiners blinded to
      patients' treatment assignment. RESULTS: Clinical and demographic characteristics
      were similar among groups at baseline. A total of 93% of the patients completed
      the intervention phase. The response rate for the 12-month follow-up period was
      84%. Except for patient satisfaction, where spinal manipulative therapy and
      exercise were superior to spinal manipulation with (P = 0.03), the group
      differences in patient-rated outcomes after 11 weeks of treatment were not
      statistically significant (P = 0.13). However, the spinal manipulative therapy
      and exercise group showed greater gains in all measures of strength, endurance,
      and range of motion than the spinal manipulation group (P < 0.05). The spinal
      manipulation with exercise group also demonstrated more improvement in flexion
      endurance and in flexion and rotation strength than the MedX group (P < 0.03).
      The MedX exercise group had larger gains in extension strength and flexion
      extension range of motion than the spinal manipulation group (P < 0.05). During
      the follow-up year, a greater improvement in patient-rated outcomes were observed
      for spinal manipulation with exercise and for MedX exercise than for spinal
      manipulation alone (P = 0.01). Both exercise groups showed very similar levels of
      improvement in patient-rated outcomes, although the spinal manipulation and
      exercise group reported greater satisfaction with care (P < 0.01). CONCLUSIONS:
      For chronic neck pain, the use of strengthening exercise, whether in combination
      with spinal manipulation or in the form of a high-technology MedX program,
      appears to be more beneficial to patients with chronic neck pain than the use of
      spinal manipulation alone. The effect of low-technology exercise or spinal
      manipulative therapy alone, as compared with no treatment or placebo, and the
      optimal dose and relative cost effectiveness of these therapies, need to be
      evaluated in future studies.

PMID- 11295903
TI  - The impact of physical function and pain on work status at 1-year follow-up in
      patients with back pain.
AB  - STUDY DESIGN: A randomized, controlled trial. OBJECTIVE: To examine the impact of
      physical function and pain on work status in patients who are long-term sick
      listed because of back pain. SUMMARY OF BACKGROUND DATA: Sickness benefit is
      granted to a person who is incapable of working because of reduced functioning.
      Improved physical function and decrease of pain may be important in considering
      return to work. METHODS: Physical performance (five activities), disability, and
      pain (self-reported questionnaires) were assessed at baseline and at the 1-year
      follow-up evaluation in 117 patients randomized to an intervention group (n = 81)
      and a control group (n = 36). RESULTS: At the 1-year follow-up evaluation, 50%
      had returned to work. Statistically significant improvements were demonstrated
      from baseline to follow-up evaluation in returners to work: in the intervention
      group on all tests and in the control group on all except two performance tests.
      Improvement measures discriminated between returners and nonreturners to work in
      the intervention group on all physical tests and a pain test and in the control
      group on three physical tests and a pain test. In the intervention group, odds
      ratios for not having returned to work were high when test measures at follow-up
      indicated markedly impaired physical function and high pain; in the control
      group, this appeared in high pain. CONCLUSIONS: Return to work was related to
      physical function and pain. More importance seemed to be attributed to physical
      performance in the intervention group than in the controls as a basis for
      returning patients to work.

PMID- 11295905
TI  - Prospective randomization of parenteral hyperalimentation for long fusions with
      spinal deformity: its effect on complications and recovery from postoperative
      malnutrition.
AB  - STUDY DESIGN: A prospective randomized study of total parenteral nutrition for
      long spinal deformity fusions as well as its effect on complications and recovery
      from postoperative malnutrition was performed. OBJECTIVES: To determine whether
      the administration of total parenteral nutrition to patients undergoing same-day
      or staged long spinal fusions has an effect on postoperative nutritional
      parameter depletion, time for return to preoperative nutritional baseline, and
      complication rate. SUMMARY OF BACKGROUND DATA: Several studies have suggested,
      but only one has demonstrated, that perioperative administration of total
      parenteral nutrition to patients undergoing spinal reconstructive surgery may
      reduce postoperative nutritional depletion, thereby decreasing postoperative
      complications. METHODS: In this study, 46 patients undergoing same-day or staged
      spinal reconstruction surgery (> or = 10 levels) were randomized to receive or
      not receive total parenteral nutrition after surgery. The nutritional parameters
      of albumin, prealbumin, transferrin, total protein, and absolute lymphocyte count
      were obtained before surgery and at regular intervals after surgery until at
      least four out of five parameters were within 10% of their preoperative baseline
      value. Perioperative data and complications were tallied. RESULTS: There were no
      complications related to total parenteral nutrition administration. There was no
      statistical difference in total complications between those who did and those who
      did not receive total parenteral nutrition. However, there was a trend (P <
      0.073) for the total parenteral nutrition group to return to nutritional baseline
      quicker. A significant increase in transferrin (P < 0.0082) and prealbumin (P <
      0.015) depletion occurred in the patients who did not receive total parenteral
      nutrition. The anterior/posterior-same-day patients receiving total parenteral
      nutrition had more major complications (P < 0.033) and significantly more total
      protein depletion (P < 0.018) than the anterior/posterior-staged patients
      receiving total parenteral nutrition, possibly because the anterior/posterior
      staged group received significantly more days(P < 0.0155) of total parenteral
      nutrition than the anterior/posterior-same-day group. In controlling for the
      number of days of total parenteral nutrition, no significant difference between
      type of surgery and complications was found. CONCLUSIONS: The administration of
      postoperative total parenteral nutrition to patients with spinal deformity is
      safe. No statistical reduction in complications occurred in the total parenteral
      nutrition group despite a trend toward more rapid normalization of nutritional
      parameters and a decrease in postoperative nutritional depletion. The
      anterior/posterior-staged group with the administration of total parenteral
      nutrition had a lower overall complication rate and a decreased incidence of
      postoperative nutritional depletion than the one-stage reconstruction group. The
      difference in the complication rates between the two groups may relate as much to
      the staging as to the administration of total parenteral nutrition per se. For
      certain cases it may be more advisable to stage patients and deliver total
      parenteral nutrition than to manage the cases in a continuous (i.e., same-day)
      fashion.

PMID- 11295906
TI  - Spinal radiation before surgical decompression adversely affects outcomes of
      surgery for symptomatic metastatic spinal cord compression.
AB  - STUDY DESIGN: A retrospective chart review was performed. OBJECTIVE: To determine
      whether preoperative spinal radiation increases the number of major wound
      complications in patients with cancer who have symptomatic spinal cord
      compression. SUMMARY OF BACKGROUND DATA: Many factors have increased the number
      of patients hospitalized with symptomatic spinal cord compression after spinal
      irradiation. The surgical management of metastatic spinal cord compression may be
      complicated by preoperative radiation. METHODS: A retrospective review of 123
      patients admitted with symptomatic metastatic spinal cord compression from 1970
      through 1996 was conducted. The final study population of 85 patients was
      separated into three treatment groups: 1) radiation only, 2) radiation followed
      by surgery, and 3) de novo surgery followed by radiation. RESULTS: The major
      wound complication rate for patients who had radiation before surgical
      decompression and stabilization was 32%, or threefold, higher than the 12%
      observed in patients who had de novo surgery (P < 0.05). No other clinical factor
      or condition predicted the development of a major wound complication. Patients
      treated initially with surgery had superior functional outcomes in an analysis
      stratified by Frankel grade (P < 0.05). Of the ambulatory patients who underwent
      de novo surgery, 75% remained ambulatory and continent 30 days after treatment,
      whereas only 50% of those treated with radiation before surgery had similar
      outcomes. CONCLUSIONS: Spinal radiation before surgical decompression for
      metastatic spinal cord compression is associated with a significantly higher
      major wound complication rate. In addition, preoperative spinal irradiation might
      adversely affect the surgical outcome.

PMID- 11295907
TI  - A technique of occipitocervical arthrodesis in children using autologous rib
      grafts.
AB  - STUDY DESIGN: Description of an operative technique with an illustrative case
      report. OBJECTIVES: The technique is presented to provide an alternative to iliac
      crest graft procedures for achieving occipitocervical fusion in children. This
      technique is particularly useful in children with instability after extensive
      decompression or laminectomy and in children with a large protuberant occiput.
      SUMMARY OF BACKGROUND DATA: The majority of techniques previously described for
      occipitocervical fusion in children rely on corticocancellous iliac crest
      autograft. Results generally have been promising; however, it can be difficult to
      harvest enough graft to span large defects after extensive decompression or to
      contour an iliac crest graft to a protuberant occiput. Structural rib autograft
      is superior in terms of availability and its unique and modifiable contour.
      Theoretical benefits of rib graft include superior strength and lower donor site
      morbidity. METHODS: The surgical technique is described. A case of a 2-year-old
      boy with Down's syndrome and myelopathy secondary to cervical instability is
      reviewed. RESULTS: The patient underwent occipitocervical arthrodesis using the
      technique described. The child made a full neurologic recovery, and at the 2
      years follow-up evaluation, the graft had incorporated and the spine was stable.
      CONCLUSION: A technique of occipitocervical arthrodesis in children is described
      using autologous rib graft. This procedure was designed to span large defects or
      to deal with a large protuberant occiput; however, it is also useful for less
      demanding cases and may offer several advantages compared with procedures relying
      on iliac crest graft.

PMID- 11295908
TI  - Traumatic atlantoaxial rotatory dislocation with odontoid fracture: case report
      and review.
AB  - STUDY DESIGN: A case of traumatic rotatory dislocation associated with odontoid
      fracture is reported. OBJECTIVES: To report a rare case of traumatic rotatory
      dislocation associated with odontoid fracture, and to discuss the mechanism
      underlying spinal instability and management. SUMMARY OF BACKGROUND DATA: This
      case is a cross between traumatic rotatory fixation and atlantoaxial rotatory
      dislocation. Classification of rotatory subluxation change after osteosynthesis
      of the odontoid process was undertaken. METHODS: A 24-year-old man sustained head
      and cervical injury after jumping. A Type 2 odontoid fracture without
      displacement was noted. RESULTS: Without further traumatic event, 1 month after
      injury, computed tomography scan showed posterior displacement of the odontoid
      fracture and Type 4 or B atlantoaxial rotatory luxation. After surgical fixation
      and reduction of the odontoid fracture, the rotatory subluxation classification
      changed and became Type 1 or A. Posterior C1-C2 arthrodesis was performed. The
      patient wore a Philadelphia cervical collar for 3 months and underwent
      physiotherapy. CONCLUSIONS: As the pivot of rotatory subluxation changed after
      odontoid process osteosynthesis, posterior C1-C2 arthrodesis was performed. The
      patient probably could have been treated in a single-stage procedure using
      posterior C1-C2 transarticular fixation with bicortical interspinous graft.

PMID- 11295909
TI  - Progressive scoliosis in cri-du-chat syndrome over a 20-year follow-up period: a
      case report.
AB  - STUDY DESIGN: A long-term follow-up study of a patient who had scoliosis
      associated with cri-du-chat syndrome was performed. OBJECTIVE: To describe for
      the first time the characteristics and natural course of progressive scoliosis in
      a patient with cri-du-chat syndrome. SUMMARY OF BACKGROUND DATA: Scoliosis is a
      common condition in patients with cri-du-chat syndrome. However, there are no
      reports on the clinical characteristics and course of this spinal deformity.
      METHODS: The current condition and radiographs of a 33-year-old man with cri-du
      chat syndrome were assessed. The records and serial radiographs of his spine were
      reviewed retrospectively over a 29-year period, between ages 4 and 33 years.
      RESULTS: The scoliosis had started before the initial radiographic examination
      and progressed rapidly during the growth period. After this stage, slow but
      continuous progression was observed over the next 10 years. The final curvature
      was quite substantial, measuring 119 degrees. CONCLUSIONS: To determine the most
      appropriate treatment for the scoliosis associated with cri-du-chat syndrome, the
      characteristics and natural course of the scoliosis should be clarified. Although
      this first report on this type of scoliosis is informative, more cases and
      further studies are needed.

PMID- 11295911
TI  - Thoracolumbar spine fractures.

PMID- 11295913
TI  - Evidence based medicine.

PMID- 11295912
TI  - Spinal manipulation can effect the response of the tibial nerve.

PMID- 11295914
TI  - Morphometry of the supra sciatic notch intrailiac implant anchor passage.
AB  - STUDY DESIGN: Anatomic study of human ilia. OBJECTIVE: To determine the anatomic
      dimensions influencing intrailiac anchor placement and design. SUMMARY OF
      BACKGROUND DATA: The development of the Galveston intrailiac implant anchor
      markedly improved results of spinal instrumentation to the pelvis. Better
      quantification of the passage dimensions is needed for the design of anatomically
      specific implants. METHODS: The length and outer diameter of two intrailiac
      anchor passages were determined from randomly selected, disease-free pairs of
      ilia from 129 white skeletons belonging to the Hamann-Todd Osteological
      Collection (Cleveland, OH, Museum of Natural History). RESULTS: Path B, an anchor
      passage running from the posterior superior iliac spine to the anterior inferior
      iliac spine, was significantly longer than path A, proceeding from the posterior
      superior iliac spine to the superior rim of the acetabulum, in adult and teenage
      males and females. For example, in adult females path B measured 141.2 +/- 7.5 mm
      versus 124.9 +/- 7.1 mm, P = or < 0.0001. The absolute minimum path A length
      available for an intrailiac post or screw anchor, following the required
      posterior superior iliac spine removal, was 80 mm in adults and male teenagers
      and 70 mm in female teenagers. For path B the hip joint was not at risk, and a
      safe anchor passage of at least 90 mm in teenagers and 110 mm in adults was
      available. The minimum thickness of the paths occurred directly above the sciatic
      notch. It was significantly larger in path A than path B, 20.2 +/- 2.4 mm versus
      14.4 +/- 3.2 mm, P < 0.0001. CONCLUSION: Of the two supra sciatic intrailiac
      paths studied, the path passing from the posterior superior iliac spine toward
      the anterior inferior iliac spine provided a longer and potentially safer anchor
      site. These studies suggest techniques for accessing longer anchor paths and the
      need for larger diameter anchors in order to achieve optimum intra iliac anchor
      stiffness and strength.

PMID- 11295915
TI  - Severity of symptoms and signs in relation to magnetic resonance imaging findings
      among sciatic patients.
AB  - STUDY DESIGN: A cross-sectional study in sciatic population. OBJECTIVES: To
      evaluate the separate roles of nerve root entrapment-based on magnetic resonance
      imaging-and other discogenic pain mechanisms on disability and physical signs
      among symptomatic sciatic patients. SUMMARY OF BACKGROUND DATA: Data symptoms of
      sciatica are generally understood to be generated by nerve root compression, but
      other pain mechanisms of sciatica have been suggested. METHODS: The authors
      obtained magnetic resonance scans from 160 patients with unilateral sciatic pain.
      The patients reported the intensity of their back and leg pain and their back
      specific disability. Clinical examination and magnetic resonance imaging (1.5 T)
      was performed on every patient. The degree of disc displacement, neural
      enhancement, and nerve root compression was evaluated from magnetic resonance
      scans. The correlations of symptoms and signs with magnetic resonance imaging
      findings were calculated. RESULTS: The degree of disc displacement in magnetic
      resonance imaging did not correlate with any subjective symptoms, nor did nerve
      root enhancement or nerve compression. Magnetic resonance imaging classification
      was associated, however, with straight leg raising restriction. In regression
      analysis, straight leg raising restriction was best explained with a simple
      classification of nonherniations versus herniations. CONCLUSIONS: The results
      suggest that a discogenic pain mechanism other than the nerve root entrapment
      generates the subjective symptoms among sciatic patients. The findings of this
      study thus indicate that magnetic resonance imaging is unable to distinguish
      sciatic patients in terms of the severity of their symptoms.

PMID- 11295917
TI  - A critical review of reviews on the treatment of chronic low back pain.
AB  - STUDY DESIGN: Systematic literature review. OBJECTIVE: To critically appraise the
      methodology of systematic reviews of conservative therapies for chronic
      nonspecific low back pain and to study the relation between the methodologic
      quality and other characteristics of these reviews. SUMMARY OF BACKGROUND DATA:
      Systematic reviews offer a concise summary of the evidence on treatment
      effectiveness, but flaws in their methodology can lead to invalid conclusions
      with serious implications for quality of patient care. METHODS: Searches of
      MEDLINE, EMBASE, Psychinfo, and the Cochrane Library were conducted. Titles,
      abstracts, and articles were reviewed by two blinded authors using three
      inclusion criteria: 1) chronic nonspecific low back pain, 2) systematic review,
      and 3) conservative treatment intervention. Data were extracted from each review
      by three authors. RESULTS: The search strategy retrieved 1102 titles and
      abstracts; 109 met inclusion criteria. A review of the full text of these
      articles excluded an additional 73 articles. Data abstraction and methodologic
      assessment were conducted on 36 articles reviewing 19 discrete interventions. The
      average quality score was 4.1, ranging from 1 (low) to 7 (high). There was a
      trend for recent reviews to be of higher quality. Fifty-six percent of the
      reviews had positive conclusions, but they had lower quality scores compared with
      those that had negative or uncertain conclusions. There were 27 (73%) qualitative
      and 10 (27%) quantitative summaries of results. CONCLUSIONS: Although the overall
      quality of systematic reviews was satisfactory, the quality of the individual
      papers included in the reviews varied considerably. The reviews often provided
      contradictory evidence on the effectiveness of a wide range of commonly used
      conservative interventions for chronic nonspecific low back pain. These findings
      illustrate the pitfalls of systematic reviews where there are a number of low
      quality trials and underscore the need for high-quality primary trials that will
      allow for more conclusive reviews.

PMID- 11295918
TI  - Re: Efficacy and validity of radiofrequency neurotomy for chroniclumbar
      zygapophysial joint pain (Spine 2000;25:1270-7).

PMID- 11295919
TI  - Successful treatment of erosive lichen planus with topical tacrolimus.

PMID- 11295921
TI  - Foreign bodies in granulomatous cutaneous lesions of patients with systemic
      sarcoidosis.
AB  - OBJECTIVE: To assess the presence of foreign material in the granulomatous
      cutaneous lesions of patients with systemic sarcoidosis. DESIGN AND SETTING:
      Observational study reevaluating histological specimens at a university referral
      hospital. PATIENTS: Sixty-five patients diagnosed as having sarcoidosis who
      developed granulomatous cutaneous involvement. MAIN OUTCOME MEASURES: To detect
      the presence of polarizable foreign particles in cutaneous biopsy specimens and
      to evaluate the association with clinical features of the patients. RESULTS:
      Granulomatous cutaneous involvement was demonstrated in 65 (15.3%) of 425
      patients with systemic sarcoidosis. In 14 (22%) of the 65 patients, the cutaneous
      biopsy specimen showed foreign particles in polarized light. The skin lesions
      corresponded to 3 different clinical patterns: an admixture of papules and
      infiltration of previously undetected minute scars (n = 6); scar sarcoidosis (n =
      4); and subcutaneous nodules (n = 4). The lesions were located most frequently in
      the extremities, involving the knees in 10 patients. CONCLUSIONS: The presence of
      polarizable foreign body material in granulomatous cutaneous lesions is not
      infrequent in patients with systemic sarcoidosis. Inoculation of foreign matter
      from a previous inapparent minor trauma may induce granuloma formation in
      individuals with sarcoidosis.

PMID- 11295923
TI  - Clinicopathologic, immunophenotypic, and molecular characterization of primary
      cutaneous follicular B-cell lymphoma.
AB  - OBJECTIVE: To determine the clinicopathologic, immunophenotypic, and molecular
      characteristics of primary follicular cutaneous B-cell lymphoma (CBCL) as defined
      by the revised European-American lymphoma classification. DESIGN: A retrospective
      survey of the medical records, an immunohistochemical study of archival biopsy
      specimens. and molecular studies of preserved DNA of all patients with follicle
      center lymphoma-follicular (FCL-F) primary CBCL from 1987 to 1997. SETTING: A
      single-center outpatient specialty clinic at an academic medical center.
      PATIENTS: Twenty-one patients (68% of all new primary CBCL cases), including 14
      men and 7 women (age range, 33-88 years; mean, 55 years). RESULTS: The head and
      neck region was the most frequent primary site. Following treatment, recurrences
      were relatively frequent, but the overall mortality rate during 1.0 to 11.3 years
      (mean, 6.3 years) of follow-up was 4.8%. Immunohistochemical analysis for B- and
      T-cell lineages was helpful in enhancing the folliclelike structures. CD10, bcl
      2, and CD43 were expressed by the neoplastic cells in 9 (47%) of 19 cases, 4
      (21%) of 19 cases, and 2 (13%) of 16 cases, respectively. Immunohistochemical
      detection of cytoplasmic immunoglobulin light chains, using steaming in EDTA as
      the antigen-retrieval technique, was successful in 12 (71%) of 17 cases. The Ig
      heavy-chain gene rearrangements, using the Southern blot technique, detected
      clonality in 17 (94%) of 18 cases. The bcl-2 gene rearrangements were detected in
      only 2 (13%) of 15 of the primary cutaneous FCL-F cases, compared with 9 (75%) of
      12 of the primary nodal FCL-F cases (P =.002). CONCLUSIONS: Primary cutaneous FCL
      F is a relatively common subtype of CBCL, with a relatively indolent course. It
      has many features in common with primary nodal FCL-F, except for low rates of bcl
      2 expression and bcl-2 gene rearrangements.

PMID- 11295924
TI  - Mucocutaneous presence of cytomegalovirus associated with human immunodeficiency
      virus infection: discussion regarding its pathogenetic role.
AB  - OBJECTIVES: To investigate the significance of cytomegalovirus (CMV) in
      mucocutaneous lesions in patients with human immunodeficiency virus (HIV), and to
      elucidate its pathogenetic role in lesions genesis. DESIGN: Retrospective (study
      1) and prospective (studies 2 and 3) surveys. SETTING: Departments of
      Dermatology, Pathology, and Microbiology at a university hospital in Madrid,
      Spain. PATIENTS: Seventeen HIV-infected patients with CMV presenting any type of
      mucocutaneous lesions (study 1); 27 HIV-positive patients with mucocutaneous
      vesicles and/or ulcers of any type and location (study 2); and 12 severely
      immunosuppressed HIV-positive volunteers (study 3). INTERVENTIONS: Mucocutaneous
      biopsy specimens from the lesions (studies 1 and 2) and from nonlesional skin
      (study 3) were analyzed by light microscopy, immunohistochemical analysis, and
      microbiological analysis (standard viral culture and shell-vial technique). MAIN
      OUTCOME MEASURES: Clinical data; histologic, immunohistochemical, and
      microbiological findings. RESULTS: (1) Studies 1 and 2: Most of the lesions where
      CMV was found were ulcers localized mainly on perianal, genital, and perigenital
      areas, usually as part of polymicrobial infections, particularly herpes simplex
      and varicella-zoster virus infections. The finding of CMV was confirmed in all
      cases by light microscopy; microbiological analysis was rarely useful. The
      finding of mucocutaneous CMV inclusions allowed their early detection in
      extracutaneous locations. (2) Study 3: Cytomegalovirus was present on healthy
      skin of the perianal area in 3 patients, and on the forearm in 1 patient.
      CONCLUSION: Cytomegalovirus does not play any significant pathogenetic role at
      least in most of the cutaneous lesions where it is found.

PMID- 11295925
TI  - Intralesional injection of mumps or Candida skin test antigens: a novel
      immunotherapy for warts.
AB  - BACKGROUND: Warts are common and induce physical and emotional discomfort.
      Numerous therapies exist, yet none is optimal. Despite theoretical advantages,
      immunotherapeutic modalities are often neglected as first-line wart therapies.
      OBJECTIVE: To compare treatment with intralesional skin test antigen injection of
      1 wart vs cryotherapy of all warts. DESIGN: Pilot study. SETTING: University
      dermatology outpatient clinic. PATIENTS: A total of 115 consecutive patients with
      at least 1 nongenital wart. INTERVENTIONS: Patients with warts were tested for
      immunity to mumps and Candida using commercial antigens. Nonresponders received
      cryotherapy and immune individuals received cryotherapy or intralesional
      injection of 1 antiserum. RESULTS: Thirty-four (30%) of the 115 patients did not
      respond to the test injections and 81 (70%) had detectable immunity. Of the
      immune group, 26 (32%) received cryotherapy, 45 (56%) received intralesional
      mumps antiserum, and 10 (12%) received intralesional Candida antiserum. Of the
      anergic patients, 28 (82%) were treated with cryotherapy; 6 (18%) refused
      cryotherapy. Of the 39 patients who were treated with immunotherapy and completed
      the protocol, 29 (74%) had complete clearing of the treated wart. Fourteen (78%)
      of 18 patients with complete resolution of their immunotherapy-treated wart also
      had resolution of untreated, distant warts. CONCLUSIONS: Intralesional injection
      of mumps or Candida antigens into warts of immune individuals represents
      effective treatment. Observation of clearing of anatomically distinct and distant
      warts suggests acquisition of human papillomavirus-directed immunity in some
      patients. We conclude that this novel approach to immunotherapy may serve as
      first-line treatment in immune individuals with multiple or large warts and as
      second-line treatment in immune patients for whom cryotherapy fails.

PMID- 11295926
TI  - Decreased skin cancer after cessation of therapy with transplant-associated
      immunosuppressants.
AB  - BACKGROUND: Immunosuppression for solid organ transplantation is associated with
      increased incidence of internal and cutaneous malignant tumors, among which skin
      cancer is the most common. OBJECTIVE: To determine the effects on cutaneous
      carcinogenesis when stopping therapy with immunosuppressive medications.
      OBSERVATIONS: We followed the clinical course of 6 solid organ transplant
      recipients after therapy with immunosuppressant medications was stopped because
      of allograft failure or unacceptable cutaneous carcinogenesis. Generally, we
      found that stopping therapy with immunosuppressive medications resulted in
      deceleration of cutaneous carcinogenesis, resolution of cutaneous verrucae
      vulgaris, and qualitative improvements in skin condition. Four patients
      experienced marked improvement; 2 did not. CONCLUSIONS: Cessation of transplant
      associated therapy with immunosuppressive medications for patients in whom
      cutaneous carcinomas developed after transplantation may lead to deceleration of
      cutaneous carcinogenesis, decreased verrucae, and improved skin quality within 1
      to 2 years. Because of the natural variation in skin cancer development and the
      small number of cases in this series, definitive conclusions require further
      study.

PMID- 11295927
TI  - Cutaneous adverse reactions to hydroxyurea in patients with sickle cell disease.
AB  - BACKGROUND: Treatment with hydroxyurea may alleviate the symptoms of sickle cell
      disease (SCD). Because treatment with hydroxyurea may be responsible for several
      cutaneous side effects and is often lifelong in patients with SCD, we conducted
      this study to evaluate the risk of cutaneous adverse reactions in SCD patients
      treated with hydroxyurea. OBSERVATIONS: Seventeen adult patients with SCD treated
      with hydroxyurea at one institution were examined by a dermatologist. Hydroxyurea
      was given for a mean of 3.04 years (range, 0.42-6.5 years). None of the patients
      had skin cancer, but 5 (29%) had disabling hydroxyurea-induced leg ulcers. Four
      of these 5 patients had a previous history of SCD ulcer, compared with none of
      the 12 patients without hydroxyurea-induced leg ulcers (P<.05). The mean age of
      patients with induced ulcers was 35.8 years and for those without ulcers was 23.5
      years (P<.01). CONCLUSIONS: Our rate of hydroxyurea-induced leg ulcers (29%) is
      higher than that reported for patients with myeloproliferative syndromes (9%). In
      addition, use of hydroxyurea has induced ulcers mainly in patients with previous
      SCD ulcers, suggesting that hydroxyurea could act in conjunction with other
      vascular abnormalities. Careful attention should be required when giving
      hydroxyurea to patients with SCD with previous ulcers as well as in older
      patients with SCD.

PMID- 11295928
TI  - Drug-induced lupus associated with COL-3: report of 3 cases.
AB  - BACKGROUND: Anti-angiogenesis is an exciting new approach to anticancer therapy.
      COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent
      preclinical anticancer activity. During the conduct of a phase 1 clinical trial
      for refractory metastatic cancer at the National Institutes of Health, we
      observed 3 individuals who developed phototoxicity followed by clinical and
      laboratory features of drug-induced lupus. OBSERVATIONS: Three of 35 patients
      treated with COL-3 developed sunburnlike eruptions accompanied by fever and a
      positive antinuclear antibody titer within 8 to 29 days of starting treatment.
      Two of 3 had positive antihistone antibody levels and arthralgia. One patient had
      marked systemic manifestations including pulmonary infiltrates and elevated
      erythrocyte sedimentation rate remittent for more than 1 year after discontinuing
      COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of
      discontinuing therapy although the serologic markers remained abnormal for the
      duration of follow-up. CONCLUSIONS: COL-3 is the second tetracycline derivative
      to be implicated in the development of drug-induced lupus. A sunburnlike eruption
      immediately preceded or accompanied the systemic and serologic changes in these 3
      patients. The rapid onset and the phototoxic appearance of the accompanying
      eruptions might suggest that damage to the keratinocytes caused the formation of
      neoantigens to which autoantibodies formed.

PMID- 11295930
TI  - The presence of foreign bodies does not exclude the diagnosis of sarcoidosis.

PMID- 11295929
TI  - Suggested rationale for prevention and treatment of glucocorticoid-induced bone
      loss in dermatologic patients.
AB  - Glucocorticoid-induced bone loss is the most predictable and debilitating
      complication of prolonged administration of systemic corticosteroids. It has been
      shown that patients treated with glucocorticoids have an increased risk of
      osteoporotic fractures, resulting in marked morbidity, particularly in elderly
      individuals. Studies on the effect of glucocorticoids on bone density and the
      efficacy of treatment regimens (namely, bisphosphonates and calcitonin) for
      preventing bone loss have been mainly on patients with asthma and rheumatologic
      diseases. However, no long-term studies have been done on the impact of prolonged
      corticosteroid treatment in dermatologic patients. The purpose of this review is
      to raise awareness about osteoporosis and new preventive measures among the
      dermatologists treating patients with glucocorticoids at high doses and for long
      periods. We summarize the assessment methods used to evaluate this condition,
      examine the results of clinical trials of drugs, and suggest a practical approach
      to managing corticosteroid osteoporosis in dermatologic patients based on data
      collected from published articles.

PMID- 11295931
TI  - Primary cutaneous follicular lymphoma.

PMID- 11295932
TI  - Time to end steroid-induced fractures.

PMID- 11295933
TI  - Rapidly enlarging, violaceous nodule on the abdomen.

PMID- 11295934
TI  - Ulcerated papules of the scrotum.

PMID- 11295935
TI  - Patchy erythema on the breasts.

PMID- 11295936
TI  - Infiltrated groin plaque in an 81-year-old man.

PMID- 11295938
TI  - Appropriate controls are essential in assessing the relationship between
      circumcision and penile dermatoses.

PMID- 11295939
TI  - Chronic urticaria.

PMID- 11295940
TI  - Cyclosporine therapy should be considered for maintenance of remission in
      patients with pemphigus.

PMID- 11295942
TI  - The restrictive covenant: just say no!

PMID- 11295943
TI  - The validation of medical histories in kindreds.

PMID- 11295944
TI  - Generalized ulcerative sarcoidosis induced by therapy with the flashlamp-pumped
      pulsed dye laser.

PMID- 11295945
TI  - Pickwickian syndrome and vanishing finger pebbles.

PMID- 11295946
TI  - Finger pebbles and diabetes: a case with broad involvement of the dorsal fingers
      and hands.

PMID- 11295947
TI  - Inpatient adverse cutaneous drug eruptions and eosinophilia.

PMID- 11295949
TI  - Hypomelanosis due to block of melanosomal maturation in amiodarone-induced
      hyperpigmentation.

PMID- 11295948
TI  - Single-dose and steady-state administration of Hypericum perforatum extract (St
      John's Wort) does not influence skin sensitivity to UV radiation, visible light,
      and solar-simulated radiation.

PMID- 11295953
TI  - Primary prevention of coronary heart disease: where do we go from here?

PMID- 11295954
TI  - Moving from compliance to conscience: why we can and should improve on the ethics
      of clinical research.

PMID- 11295955
TI  - Report of the Council on Scientific Affairs: preventing needlestick injuries in
      health care settings.
AB  - Needlestick injuries continue to pose a significant risk to health care workers;
      however, appropriate use of needlestick prevention devices, especially in
      comprehensive prevention programs, can significantly reduce the incidence of such
      injuries. Cost analyses indicate that use of these devices will be cost-effective
      in the long term. To provide more scientific and cost data on the efficacy of
      needlestick prevention devices, recording of needlestick injuries must be
      improved. Federal law now requires the use of safety-engineered sharps devises to
      protect health care workers, and state-level legislation on the use and
      evaluation of needlestick prevention devices is under consideration. Health care
      employers should evaluate the implementation of needlestick prevention devices
      with the participation of employees who will use such devices and, where
      appropriate, introduce such devices accompanied by the necessary education and
      training, as part of a comprehensive sharps injury prevention and control
      program.

PMID- 11295956
TI  - Antithrombotic therapy in patients with acute coronary syndromes.
AB  - The potential armamentarium of agents used in the treatment of acute coronary
      syndromes continues to expand, including such well-tested agents as aspirin,
      unfractionated heparin, and earlier-generation fibrinolytic agents, and newer
      agents such as low-molecular-weight heparins, direct thrombin inhibitors,
      thienopyridines, platelet glycoprotein IIb/IIIa receptor inhibitors, and bolus
      administration fibrinolytic agents. Older and newer antithrombotic agents have
      undergone and continue to undergo intensive clinical investigation in patients
      with the clinical spectrum of acute coronary syndromes, which includes unstable
      angina, non-Q-wave (non-ST-segment elevation) myocardial infarction, and ST
      segment elevation myocardial infarction. These studies, often conducted on an
      international scope and involving thousands of patients, provide data allowing
      practitioners to optimize the care of patients with acute coronary syndromes. In
      this article, studies of these established and newer agents in the treatment of
      patients with acute coronary syndromes are reviewed critically and summarized.
      Recommendations regarding use of antithrombotic agents in patients with acute
      coronary syndromes are then given.

PMID- 11295957
TI  - Applicability of cholesterol-lowering primary prevention trials to a general
      population: the framingham heart study.
AB  - BACKGROUND: Four large trials have shown cholesterol-reduction therapy to be
      effective for primary prevention of coronary heart disease (CHD). METHODS: To
      determine the generalizability of these trials to a community-based sample, we
      compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C)
      distributions of patients in the 4 trials with those of Framingham Heart Study
      subjects. Lipid profiles that have not been studied were identified. Twelve-year
      rates of incident CHD were compared between subjects who met eligibility criteria
      and those who did not. RESULTS: The Framingham sample included 2498 men and 2870
      women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility
      criteria for each of the 4 trials based on their lipid levels; 60.2% met
      eligibility criteria for at least 1 trial. For the 1 trial that included women,
      20.2% of Framingham women met eligibility criteria. In general, subjects with
      desirable total cholesterol levels and lower HDL-C levels and subjects with
      average total cholesterol levels and average to higher HDL-C levels have not been
      included in these trials. Among subjects who developed incident CHD during follow
      up, 25.1% of men and 66.2% of women would not have been eligible for any trial.
      Most ineligible subjects who developed CHD had isolated hypertriglyceridemia
      (>2.25 mmol/L [>200 mg/dL]). CONCLUSIONS: In our sample, 40% of men and 80% of
      women had lipid profiles that have not been studied in large trials to date. We
      observed a large number of CHD events in "ineligible" subjects in whom
      hypertriglyceridemia was common. Further studies are needed to define the role of
      lipid-lowering therapy vs other strategies for primary prevention in the general
      population.

PMID- 11295958
TI  - Dose discrepancies between the Physicians' Desk Reference and the medical
      literature, and their possible role in the high incidence of dose-related adverse
      drug events.
AB  - BACKGROUND: Adverse drug events (ADEs) are a major cause of morbidity and
      mortality, and even minor ADEs may adversely affect patients' compliance with
      treatment. Because most ADEs are dose-related phenomena, adjusting drug dosages
      to account for individual patients' needs and tolerances is fundamental to good
      therapeutics. OBJECTIVE: To determine whether the Physicians' Desk Reference
      (PDR), the leading source of drug information for physicians, provides the full
      range of effective drug doses, especially the lowest, least ADE-prone doses of
      medications, for physicians to consider in treating patients. METHODS: Review of
      dosage guidelines and dose-response information in the PDR. Comparison with dose
      response data obtained from articles listed in MEDLINE from 1966 to 2000.
      RESULTS: For many types of medications, physicians are frequently advised to use
      the lowest effective doses of drugs, especially initially. Yet, effective low
      doses determined in prerelease studies or in postrelease work are often omitted
      from the PDR, even when they have been recommended by expert panels. CONCLUSIONS:
      Optimal therapeutics depends on the availability of comprehensive information.
      However, the PDR contains only the limited dose information from package inserts.
      Because the PDR was originally developed as a promotional device, there is no
      mechanism by which all clinically relevant dose-response data or important
      postrelease discoveries are regularly and rapidly incorporated into it. Thus, a
      gap exists in the availability of current and comprehensive dose information for
      physicians. This article provides information on lower, effective doses for 48
      major medications, with an extensive reference list-a compilation of low-dose
      information not previously published, to our knowledge, in the medical
      literature. Physicians must have a readily accessible source of current and
      complete dose-response information to individualize drug therapy and minimize the
      risks of ADEs.

PMID- 11295959
TI  - Efficacy of different drug classes used to initiate antihypertensive treatment in
      black subjects: results of a randomized trial in Johannesburg, South Africa.
AB  - BACKGROUND: Thiazides are recommended to initiate antihypertensive drug treatment
      in black subjects. OBJECTIVE: To test the efficacy of this recommendation in a
      South African black cohort. METHODS: Men and women (N = 409), aged 18 to 70
      years, with a mean ambulatory daytime diastolic blood pressure between 90 and 114
      mm Hg, were randomized to 13 months of open-label treatment starting with the
      nifedipine gastrointestinal therapeutic system (30 mg/d, n = 233), sustained
      release verapamil hydrochloride (240 mg/d, n = 58), hydrochlorothiazide (12.5
      mg/d, n = 58), or enalapril maleate (10 mg/d, n = 60). If the target of reducing
      daytime diastolic blood pressure below 90 mm Hg was not attained, the first-line
      drugs were titrated up and after 2 months other medications were added to the
      regimen. RESULTS: While receiving monotherapy (2 months, n = 366), the patients'
      systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg
      for nifedipine, 17/11 mm Hg for verapamil, 12/8 mm Hg for hydrochlorothiazide,
      and 5/3 mm Hg for enalapril. At 2 months the blood pressure of more patients
      treated with nifedipine was controlled: 133 (63.3%, P</=.03) vs 20 (39.9%)
      receiving verapamil, 21 (40.4%) receiving hydrochlorothiazide, and 11 (20.8%)
      receiving enalapril. At 13 months (n = 257), more patients (P<.001) continued
      receiving monotherapy with nifedipine (94/154 [61.0%]) or verapamil (22/35
      [62.9%]) than hydrochlorothiazide (10/39 [25.6%]) or enalapril (1/29 [3.4%]). A
      sustained decrease of left ventricular mass (P<.001) with no between-group
      differences was achieved at 4 and 13 months. CONCLUSIONS: In contrast to current
      recommendations, calcium channel blockers are more effective than thiazides as
      initial treatment in black subjects with hypertension. If treatment is started
      with thiazides or converting-enzyme inhibitors, combination therapy is more
      likely to be required to control blood pressure and reduce left ventricular mass.

PMID- 11295960
TI  - Connective tissue disease and other rheumatic conditions following cosmetic
      breast implantation in Denmark.
AB  - OBJECTIVE: To examine the occurrence of connective tissue diseases (CTDs) as well
      as ill-defined and other rheumatic conditions among Danish women with cosmetic
      silicone breast implants. PATIENTS AND METHODS: A total of 2761 women with breast
      implants and 8807 control subjects were identified from plastic surgery private
      clinics and from public hospital plastic surgery departments. Women operated on
      at plastic surgery private clinics were identified through the files of each
      clinic, while women operated on at public hospitals were identified using the
      nationwide Danish National Registry of Patients. The control group consisted of
      women who underwent cosmetic surgery other than breast implantation or who only
      had a consultation. All women were followed up from January 1, 1977, through
      December 31, 1996, through the Danish National Registry of Patients for the
      occurrence of CTD as well as ill-defined and other rheumatic conditions. For the
      study period January 1, 1977, through December 31, 1994, the Danish National
      Registry of Patients contains information on hospitalization only, whereas data
      on outpatient visits are included from 1995 on, thus improving the sensitivity of
      the data. The implant and control groups were compared with the Danish population
      rates for CTD and ill-defined and other rheumatic conditions, and a direct
      comparison between the implant and control groups was also performed. RESULTS:
      When compared with rates from the general population, no excess of definite CTD
      was observed in the implant cohorts. For ill-defined and other rheumatic
      conditions, statistically significant excesses of unspecified rheumatism were
      observed in both the implant and control cohorts when compared with national
      rates. A direct comparison between the implant and control cohorts found no
      material differences between the groups. CONCLUSIONS: The findings of this study
      support previous investigations and independent review panel conclusions that an
      association between silicone breast implants and definite CTDs is unlikely. The
      observation of an excess of unspecified rheumatism among women with implants and
      among control women suggests that women undergoing cosmetic plastic surgery have
      hospitalization rates for this condition in excess of those from the general
      population.

PMID- 11295961
TI  - Cigarette smoking, alcohol consumption, and risk of hip fracture in women.
AB  - BACKGROUND: Previous studies regarding the impact of cigarette smoking on the
      risk of hip fracture in postmenopausal women have been inconsistent, suggesting
      different effects in different groups. The effect of alcohol intake on fracture
      risk is puzzling: moderate alcohol intake appears to increase bone density, and
      its association with hip fracture is not clear. METHODS: To assess the
      associations of cigarette smoking and alcohol consumption with hip fracture risk
      among postmenopausal women, we conducted an analysis of a population-based case
      control study from Sweden. Cases were postmenopausal women, aged 50 to 81 years,
      who sustained a hip fracture after minor trauma between October 1, 1993, and
      February 28, 1995; controls were randomly selected from a population-based
      register during the same period. A mailed questionnaire requesting information on
      lifestyle habits and medical history was used 3 months after the hip fracture for
      cases and simultaneously for controls. Age-adjusted odds ratios (ORs) and 95%
      confidence intervals (CIs) were computed by means of logistic regression.
      RESULTS: Of those eligible, 1328 cases (82.5%) and 3312 controls (81.6%)
      responded. Compared with never smokers, current smokers had an increased risk of
      hip fracture (age-adjusted OR, 1.66; 95% CI, 1.41-1.95). Duration of smoking
      particularly postmenopausal smoking-was more important than the amount smoked.
      Former smokers had a small increase in risk (age-adjusted OR, 1.15; 95% CI, 0.97
      1.37) that decreased with the duration of cessation. The age-adjusted OR for
      women consuming alcohol was 0.80 (95% CI, 0.69-0.93). CONCLUSIONS: Cigarette
      smoking is a risk factor for hip fracture among postmenopausal women; risk
      decreases after cessation. Alcohol consumption has a weak inverse association
      with risk.

PMID- 11295962
TI  - A retrospective study of general hospital patients who commit suicide shortly
      after being discharged from the hospital.
AB  - OBJECTIVE: To assess the scope of diagnostic screening for suicide prevention in
      general hospital patients. METHODS: Retrospective medical record review of
      general hospital patients who committed suicide and matched-control subjects who
      did not commit suicide shortly after being discharged from the hospital. RESULTS:
      The suicide rate was 32 per 100 000 patient-years. Eight (73%) of 11 patients who
      committed suicide were diagnosed with depression, substance use disorder, or both
      at their last hospital admission compared with 11 (33%) of the controls (P<.05).
      Only 1 of 44 patients (both cases and controls) was referred for psychiatric
      consultation. CONCLUSIONS: The suicide rate in general hospital patients was
      almost 3-fold higher than in the general population. Depression and/or substance
      use disorders were risk factors for suicide. Screening for those disorders may be
      beneficial for suicide prevention in the general hospital population, but will
      likely benefit more patients who will not commit suicide.

PMID- 11295963
TI  - Risk factors for congestive heart failure in US men and women: NHANES I
      epidemiologic follow-up study.
AB  - BACKGROUND: The incidence of congestive heart failure (CHF) has been increasing
      steadily in the United States during the past 2 decades. We studied risk factors
      for CHF and their corresponding attributable risk in the First National Health
      and Nutrition Examination Survey Epidemiologic Follow-up Study. PARTICIPANTS AND
      METHODS: A total of 13 643 men and women without a history of CHF at baseline
      examination were included in this prospective cohort study. Risk factors were
      measured using standard methods between 1971 and 1975. Incidence of CHF was
      assessed using medical records and death certificates obtained between 1982 and
      1984 and in 1986, 1987, and 1992. RESULTS: During average follow-up of 19 years,
      1382 CHF cases were documented. Incidence of CHF was positively and significantly
      associated with male sex (relative risk [RR], 1.24; 95% confidence interval [CI],
      1.10-1.39; P<.001; population attributable risk [PAR], 8.9%), less than a high
      school education (RR, 1.22; 95% CI, 1.04-1.42; P =.01; PAR, 8.9%), low physical
      activity (RR, 1.23; 95% CI, 1.09-1.38; P<.001; PAR, 9.2%), cigarette smoking (RR,
      1.59; 95% CI, 1.39-1.83; P<.001; PAR, 17.1%), overweight (RR, 1.30; 95% CI, 1.12
      1.52; P =.001; PAR, 8.0%), hypertension (RR, 1.40; 95% CI, 1.24-1.59; P<.001;
      PAR, 10.1%), diabetes (RR, 1.85; 95% CI, 1.51-2.28; P<.001; PAR, 3.1%), valvular
      heart disease (RR, 1.46; 95% CI, 1.17-1.82; P =.001; PAR, 2.2%), and coronary
      heart disease (RR, 8.11; 95% CI, 6.95-9.46; P<.001; PAR, 61.6%). CONCLUSIONS:
      Male sex, less education, physical inactivity, cigarette smoking, overweight,
      diabetes, hypertension, valvular heart disease, and coronary heart disease are
      all independent risk factors for CHF. More than 60% of the CHF that occurs in the
      US general population might be attributable to coronary heart disease.

PMID- 11295964
TI  - Fludeoxyglucose positron emission tomography in the diagnosis of giant cell
      arteritis.
AB  - We describe a case in which fludeoxyglucose F 18 positron emission tomography
      (PET) led directly to the diagnosis of giant cell arteritis in an elderly woman
      with a fever of unknown origin. The patient presented with a 3-month history of
      fatigue, fever, headache, visual disturbance, jaw claudication, and anemia. A
      computed tomographic scan showed an anterior mediastinal mass that was suspected
      of being malignant. A fludeoxyglucose F 18 PET scan performed for preoperative
      evaluation identified striking uptake of fludeoxyglucose F 18 in the walls of the
      entire aorta, left main coronary artery, and subclavian, carotid, and common
      iliac arteries bilaterally, suggestive of an arteritis, a diagnosis subsequently
      confirmed by the findings of an arterial biopsy. Her erythrocyte sedimentation
      rate was 129 mm/h. There was normalizaton of the PET scan 2 weeks following
      treatment with prednisolone. This case suggests that fludeoxyglucose F 18 PET
      contributes to the noninvasive diagnosis of giant cell arteritis, as well as to
      the evaluation of the extent of disease, response to therapy, and disease
      recurrence.

PMID- 11295965
TI  - Polyarteritis nodosa presenting as an acute bilateral epididymitis.

PMID- 11295966
TI  - Cavernous sinus syndrome due to vaccination-induced giant cell arteritis.

PMID- 11295967
TI  - Idiopathic spontaneous hemoperitoneum.

PMID- 11295968
TI  - Pituitary gangliocytoma-adenoma presenting with acromegaly: response to
      treatment.

PMID- 11295969
TI  - Safety of statins (hydroxymethyl glutaryl coenzyme a reductase inhibitors):
      different mechanisms of metabolism and drug transport may have clinical
      relevance.

PMID- 11295972
TI  - Non-A, non-B fulminant hepatic failure.

PMID- 11295973
TI  - Do silver alloy catheters increase the risk of systemic argyria?

PMID- 11295975
TI  - Minimum intensity anticoagulation therapy as primary prevention strategy.

PMID- 11295977
TI  - Buerger disease or arsenic intoxication?

PMID- 11295979
TI  - St John's Wort and literature quotations.

PMID- 11295980
TI  - Personnel-to-patient transmission of hepatitis C virus: underestimation of
      exposure.

PMID- 11295982
TI  - Protecting the brains of patients after heart surgery.

PMID- 11295983
TI  - Subcortical infarctions, transcranial Doppler, and cerebral vasomotor reactivity.

PMID- 11295984
TI  - One-stop shopping: stroke questions further answered with magnetic resonance
      imaging.

PMID- 11295985
TI  - Guglielmi detachable coiling for intracranial aneurysms: the story so far.
AB  - Spontaneous rupture of cerebral aneurysms typically results in subarachnoid
      hemorrhage. The primary goal of treatment of cerebral aneurysms is to prevent
      future rupture. Surgical clipping had been the mainstay of treatment of both
      ruptured and unruptured cerebral aneurysms. In 1991, Guglielmi detachable coil
      (GDC) embolization was introduced as an alternative method for treating selected
      patients with aneurysm. The goal of the treatment is prevent the flow of blood
      into the aneurysm sack by filling the aneurysm with coils and thrombus.
      Theoretically, there are several advantages of GDC over surgery. These procedures
      are performed under general anesthesia with the standard transfemoral approaches
      used in diagnostic angiography. Since its inception, GDC embolization has evolved
      as a result of both clinical experience and the introduction of technological
      improvements. We are now better at selecting aneurysms appropriate for coiling,
      which also have wide necks. Advances in GDC technology have also improved this
      method of treatment. Over the last several years, the number of coil sizes has
      been increased, multidimensional coils allowing safer initial coil placement have
      become available, and, more recently, softer coils have been introduced. Our
      current approach is to have both surgical and endovascular options for patients.

PMID- 11295986
TI  - Stroke prevention and treatment in sickle cell disease.
AB  - While the problem of stroke in the patients with sickle cell disease (SCD) has
      been known for more than 75 years, adequate preventive and treatment strategies
      are just now being tested. Recent data on prevalence and incidence have been
      obtained from the Cooperative Study of Sickle Cell Disease of more than 4000
      patients with SCD observed in 23 US clinical centers over a 10-year period.1 The
      overall age-specific incidence of first stroke in SCD (homozygous sickle cell
      anemia) is low (0.13%) at ages younger than 24 months, increasing to just over 1%
      at ages 2 to 5 years, with only a slight decrement to 0.79% at ages 6 to 9 years.
      The risk of brain infarction declines until a second peak is seen at ages older
      than 50 years, when the incidence again increases to nearly 1.3%. Although
      intracranial hemorrhage does occur in young children with SCD, the risk is low
      compared with older children and adults. The Cooperative Study of Sickle Cell
      Disease reported risk factors for infarction to be prior transient ischemic
      attack, low steady-state hemoglobin values, and rate and recency of episodes of
      acute chest syndrome, as well as elevated systolic blood pressure. Risk factors
      for intracranial hemorrhage included low steady-state hemoglobin values and a
      high leukocyte count. The burden of cerebrovascular disease is even higher if
      subclinical magnetic resonance imaging (MRI) lesions, presumed to be ischemic,
      are included. The prevalence of such lesions is more than 22% in patients with
      SCD, and most of these patients have not reported symptoms, although specialized
      neuropsychological testing shows lower scores in children with silent lesions on
      MRI scans. Patients with a history of clinical stroke typically have infarcts in
      the cortex and deep white matter, whereas silent infarcts tend to be more limited
      to deep white matter. Common infarction patterns are characterized by wedge
      shaped lesions of large-vessel territories; border zone infarctions, particularly
      of the middle and cerebral artery watershed region; and small punctate lesions of
      the deep white matter. Fat embolism to the brain and venous thromboses are
      encountered rarely.

PMID- 11295987
TI  - Diffusion- and perfusion-weighted brain magnetic resonance imaging in patients
      with neurologic complications after cardiac surgery.
AB  - BACKGROUND: Neurologic complications after cardiac surgery include stroke,
      encephalopathy, and persistent cognitive impairments. More precise neuroimaging
      of patients with these complications may lead to a better understanding of the
      etiology and treatment of these disorders. OBJECTIVE: To study the pattern of
      ischemic changes on diffusion- and perfusion-weighted magnetic resonance imaging
      (DWI, and MRPI, respectively) in patients with neurologic complications after
      cardiac surgery. METHODS: All records were reviewed of our patients undergoing
      cardiac surgery in the previous year who also underwent postoperative DWI or
      MRPI. Neurologic symptoms, vascular studies, and the pattern of ischemic changes
      were recorded. Acute ischemic lesions were classified as having a territorial,
      watershed, or lacunar pattern of infarction. Patients with multiple territorial
      infarcts in differing vascular distributions that were not explained by occlusive
      vascular lesions were classified as having multiple emboli. RESULTS: Fourteen
      patients underwent DWI and 4 underwent MRPI. Acute infarcts were found in 10 of
      14 patients by DWI as compared with 5 of 12 patients by computed tomography.
      Eight patients presented with encephalopathy (associated with focal neurologic
      deficits in 4), 4 with focal deficits alone, and 2 with either fluctuating
      symptoms or transient ischemic attacks. Among patients with encephalopathy, 7 of
      8 had patterns of infarction suggestive of multiple emboli, including 3 of 4
      patients with no focal neurologic deficits. Several patients had combined
      watershed and multiple embolic patterns of ischemia. Findings of MRPI studies
      were abnormal in 2 of 4 patients, showing diffusion-perfusion mismatch; both
      patients had either fluctuating deficits or transient ischemic attacks, and their
      conditions improved with blood pressure manipulation. CONCLUSIONS: In patients
      with neurologic symptoms after cardiac surgery, DWI is more sensitive to ischemic
      change than computed tomographic scanning and can demonstrate patterns of
      infarction that may help us understand etiology. The most common pattern was
      multiple embolic infarcts. Preliminary experience with MRPI suggests that some
      patients have persistent diffusion-perfusion mismatch after surgery and may
      benefit from therapeutic intervention.

PMID- 11295988
TI  - Cerebrovascular reactivity and subcortical infarctions.
AB  - OBJECTIVES: To investigate the association between different kinds of ischemic
      lesions and cerebrovascular reactivity (CR) and to evaluate their relationships
      with the major risk factors for stroke. SUBJECTS AND METHODS: We evaluated CR
      using the breath-holding index technique during bilateral transcranial Doppler
      monitoring of flow velocity in the middle cerebral arteries of 41 consecutive
      patients attending our clinic for a recent, first-ever, ischemic stroke and in 15
      control subjects. Based on the location of the lesion determined by computed
      tomography, the following 3 types of infarctions were identified: cortical (or
      territorial), single subcortical, and subcortical with multiple silent
      subcortical infarctions. Patients with a condition of severe carotid artery
      stenosis or occlusion, which in itself could account for altered CR, were
      excluded from this study. All physiological and pathologic conditions that could
      possibly cause an impairment in CR were recorded. RESULTS: The breath-holding
      index was significantly lower in the multiple subcortical infarctions group than
      in the control subjects (P < .001), single subcortical infarctions group (P <
      .01), and cortical infarctions group (P < .01). In all of the groups male sex (P
      < .05) and a history of hypertension (P < .05), regardless of whether
      hypertension was treated, correlated with low CR. The multiple regression
      analysis indicated that the only significant factor able to influence the breath
      holding index was the type of lesion. CONCLUSIONS: Nonstenotic patients with
      first-ever stroke who had a recent symptomatic subcortical infarction associated
      with multiple silent infarctions seem to have an impaired cerebrovascular reserve
      capacity. The strong association of subcortical infarctions with multiple silent
      infarctions with low CR indicates the role of small vessel vasculopathy and
      hypoperfusion as possible pathogenetic mechanisms of subcortical infarctions with
      multiple silent infarctions.

PMID- 11295989
TI  - Prediction of hemorrhagic transformation following acute stroke: role of
      diffusion- and perfusion-weighted magnetic resonance imaging.
AB  - BACKGROUND: Acute diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic
      resonance imaging (MRI) findings may correlate with secondary hemorrhagic
      transformation (HT) risk in patients with stroke. This information could be of
      value, particularly in individuals being considered for thrombolytic therapy.
      OBJECTIVE: To determine the relationship between DWI and PWI findings and the
      risk of secondary HT in patients with acute stroke. DESIGN: Retrospective case
      series. SETTING: Academic medical center. PATIENTS: Twenty-seven patients with
      acute stroke capable of being evaluated with DWI/PWI 8 hours or less after
      symptom onset. MAIN OUTCOME MEASURES: Apparent diffusion coefficient values,
      perfusion delay measurements, and subsequent MRI or computed tomographic scans
      detected HT. RESULTS: The mean +/- SD apparent diffusion coefficient of ischemic
      regions that experienced HT was significantly lower than the overall mean +/- SD
      apparent diffusion coefficient of all ischemic areas analyzed (0.510 +/- 0.140 x
      10(-3) mm(2)/s vs 623 +/- 0.113 x 10(-3) mm(2)/s; P =.004). This difference
      remained significant when comparing the HT-destined ischemic areas with the non
      HT-destined areas within the same ischemic lesion (P =.02). Patients receiving
      recombinant tissue-type plasminogen activator (rt-PA) experienced HT
      significantly earlier than patients not receiving rt-PA (P =.002). Moreover, a
      persistent perfusion deficit in the area of subsequent hemorrhage at 3 to 6 hours
      after the initial MRI scan was identified in significantly more patients who
      experienced HT than in those who did not (83% vs 30%; P =.03). CONCLUSION: Both
      DWI and PWI scans detect abnormalities that are associated with HT. These
      findings support a role for MRI in identifying patients who are at increased risk
      for secondary HT following acute ischemic stroke.

PMID- 11295990
TI  - Cognitive changes 5 years after coronary artery bypass grafting: is there
      evidence of late decline?
AB  - OBJECTIVE: To determine the long-term (preoperative to 5 years postoperative) and
      late (1-5 years postoperative) changes in cognitive test performance in patients
      after coronary artery bypass grafting. SETTING: The departments of surgery and
      neurology at The Johns Hopkins University School of Medicine, Baltimore, Md.
      PATIENTS: A group of 102 patients who completed preoperative and follow-up
      cognitive testing up to 5 years after coronary artery bypass grafting. MAIN
      OUTCOME MEASURES: A battery of neuropsychological tests, assessing 8 cognitive
      domains (attention, language, verbal and visual memory, visuoconstruction,
      executive function, and psychomotor and motor speed), was administered
      preoperatively and at 1 month, 1 year, and 5 years postoperatively. RESULTS:
      Significant changes in neuropsychological test scores from baseline to 5 years
      were observed in only 3 of the 8 domains: there were declines in
      visuoconstruction and psychomotor speed and an improvement in executive function.
      When the period from baseline to 5 years was divided into 2 intervals, we found
      that cognitive test scores generally improved from baseline to 1 year. By
      contrast, between 1 and 5 years, there was significant decline in all cognitive
      domains except for attention and executive function. Some potential explanatory
      covariates (demographic, medical history, and surgery variables) were associated
      with changes from baseline to 5 years in some cognitive domains, but few
      covariates were statistically significant in more than 1 cognitive domain.
      CONCLUSIONS: The change in cognitive test performance between baseline and 5
      years is likely related to several factors, including low baseline performance
      and practice effects. The significant decline in performance between 1 and 5
      years, however, raises the possibility that a late cognitive decline may be
      occurring in this population. Additional studies, with the use of a nonsurgical
      control group, are needed to determine if the observed cognitive decline is
      related to bypass surgery itself, normal aging in a population with
      cardiovascular risk factors, or some combination of these and other factors.

PMID- 11295991
TI  - Stroke with internal carotid artery stenosis.
AB  - BACKGROUND: Stroke patterns in patients with different degrees of carotid
      stenosis have not been systematically studied. OBJECTIVE: To determine first-ever
      stroke subtypes in nonselected patients with extracranial internal carotid artery
      (ICA) stenosis, based on a primary care hospital stroke registry. METHODS: One
      hundred seventy-three patients who experienced their first-ever stroke and who
      had 50% or greater (North American Symptomatic Carotid Endarterectomy Trial
      method) ipsilateral extracranial ICA stenosis, corresponding to 6.5% of 2649
      patients with anterior circulation stroke included in the Lausanne Stroke
      Registry, were studied. All these patients underwent Doppler ultrasonography,
      carotid angiography (conventional or magnetic resonance angiography),
      neuroimaging (computed tomography or magnetic resonance imaging), and other
      investigations from the standard protocol of the Lausanne Stroke Registry.
      RESULTS: We found the following types of infarct in the middle cerebral artery
      territory: anterior pial in 54 (31%) of the patients; subcortical, 34 (20%);
      posterior pial, 32 (19%); large hemispheral, 20 (12%); and border zone, 17 (10%).
      There were multiple pial in 14 (8%) and multiple deep infarcts in 2 (1%) of the
      patients. Moderate (50%-69%) ICA stenosis was significantly associated with large
      hemispheral infarcts and a normal contralateral ICA (P =.04 and P =.02,
      respectively). Seventy percent to 89% of ICA stenosis was associated with prior
      transient ischemic attacks (P =.02). After adjusting for cardioembolism, border
      zone infarcts showed a strong trend to appear mostly in patients with 90% to 99%
      ICA stenosis (P =.06). CONCLUSIONS: The association of a large hemispheral
      infarct with moderate ICA stenosis suggests a large embolism and/or an inadequate
      collateral supply. While an embolism may also contribute, the association of
      border zone infarcts with 90% to 99% ICA stenosis emphasizes the significance of
      hemodynamic disturbance in the pathogenesis of these types of infarct.

PMID- 11295992
TI  - Evolution of cerebral infarct volume assessed by diffusion-weighted magnetic
      resonance imaging.
AB  - BACKGROUND: Knowledge of the natural evolution of ischemic brain lesions may be a
      crucial aspect in the assessment of future stroke therapies. OBJECTIVE: To
      establish daily changes of ischemic cerebral lesion volume using diffusion
      weighted magnetic resonance imaging. DESIGN: Prospective cohort study. SETTING:
      Referral center. PATIENTS AND METHODS: Serial magnetic resonance imaging scans
      were performed in consecutive untreated stroke patients. The baseline scan was
      obtained within 48 hours after symptom onset; subsequent scans, 12 to 48 hours, 3
      to 4 days, 5 to 7 days, and 30 days after baseline. Lesion volumes were measured
      on each scan by 2 independent observers. MAIN OUTCOME MEASURE: Daily change in
      lesion volume. RESULTS: A total of 112 magnetic resonance imaging scans were
      obtained in 24 patients. An early increase in lesion volume was seen in all
      patients. Maximum lesion volume was reached at a mean of 74 hours. Lesion volumes
      increased by a mean (+/- SEM) of 21% +/- 12% during day 2 and 10% +/- 12% during
      day 3. No significant change occurred during day 4. During days 5, 6, and 7,
      statistically significant mean (+/- SEM) decreases of 6% +/- 8%, 3% +/- 4%, and
      4% +/- 5%, respectively, were observed. CONCLUSIONS: Ischemic lesions follow a
      relatively consistent pattern of growth during the first 3 days and subsequent
      decrease in size. These data in conjunction with data regarding the evolution of
      lesion volume during the first 24 hours after symptom onset may be useful in the
      design of pilot studies of therapies for acute stroke.

PMID- 11295993
TI  - Diffusion-weighted imaging and National Institutes of Health Stroke Scale in the
      acute phase of posterior-circulation stroke.
AB  - BACKGROUND: Occlusive disease of the posterior circulation represents a
      heterogeneous group of strokes that differ in etiology, clinical presentation,
      and prognosis. Computed tomography provides suboptimal visualization of posterior
      circulation infarcts. Anatomic definition of traditional magnetic resonance
      imaging sequences has been used for clinicoradiologic correlation in patients
      with posterior-circulation disease. These studies focused on the subacute rather
      than the acute phase of ischemia. Lesion volumes on diffusion-weighted imaging
      (DWI) and perfusion imaging were found to have a good correlation with 24-hour
      National Institutes of Health stroke scale (NIHSS) score in ischemia of the
      anterior circulation. Correlation between NIHSS score and lesion volume in
      posterior-circulation infarcts is unknown. OBJECTIVES: To investigate whether DWI
      is useful for clinicoradiologic correlation of posterior-circulation ischemia
      within 24 hours after symptom onset and whether NIHSS score correlates with
      lesion volumes in patients with posterior-circulation stroke. PATIENTS AND
      METHODS: In a database analysis of 631 patients with stroke from June 26, 1996,
      to July 30, 1999, 115 patients (18%) had symptoms of posterior-circulation
      ischemia by imaging and clinical criteria. Among these 115, we included all
      patients (n = 40) who underwent DWI within 24 hours from symptom onset (mean, 9.7
      +/- 7.1 hours). All 40 patients also underwent magnetic resonance angiography and
      T2-weighted imaging. Seventy-five did not meet inclusion criteria: in 45,
      magnetic resonance imaging was performed more than 24 hours after symptom onset;
      12 did not have DWI; in 11 patients, symptoms resolved within 24 hours; 6 had
      hemorrhages; and 1 had a border zone infarct. RESULTS: An acute lesion on DWI
      corresponding to the patient's symptoms was detected in all 40 patients, 16 (40%)
      of whom had detectable acute lesions on T2-weighted images. The lesions on DWI
      were larger in 11 of the 16 patients with positive T2-weighted images. Acute
      lesion volume did not correlate with NIHSS score (n = 40; rho = 0.30; P =.06,
      Spearman rank) also when DWI lesion volumes were divided by cause and territory.
      CONCLUSIONS: Diffusion-weighted imaging is more effective than T2-weighted
      imaging in patients with acute posterior-circulation strokes. The DWI lesion
      volume did not significantly correlate with NIHSS score, suggesting that NIHSS is
      more weighted toward anterior-circulation stroke symptoms.

PMID- 11295994
TI  - Multiple simultaneous intracerebral hemorrhages: clinical features and outcome.
AB  - BACKGROUND: The simultaneous occurrence of intracerebral hemorrhages in different
      arterial territories is an uncommon clinical event. Its predisposing factors and
      pathophysiological mechanisms are not clearly defined. OBJECTIVE: To analyze the
      frequency, risk factors, clinical features, neuroimaging findings, and outcome of
      multiple simultaneous intracerebral hemorrhages (SIHs). PATIENTS AND METHODS: We
      studied all patients with acute stroke admitted to our hospital from July 18,
      1997, through December 18, 1999. Multiple SIHs were defined as the presence of 2
      or more intracerebral hemorrhages affecting different arterial territories with
      identical computed tomographic density profiles. Patients with a history of
      traumatic brain injury were excluded from this study. Diagnostic investigation
      included routine blood and urine tests, coagulation studies, a chest radiograph,
      electrocardiogram, 2-dimensional transthoracic echocardiography, and computed
      tomography of the head without contrast medium. Disability was assessed using the
      National Institutes of Health Stroke Scale and Modified Rankin Scale. RESULTS:
      Among 142 patients with hemorrhagic stroke, we found 4 (2.8%) with SIHs. All 4
      patients had a history of uncontrolled arterial hypertension. We excluded other
      potential causes of multiple SIHs by using appropriate diagnostic tests. The most
      common clinical manifestations were headache and weakness. Localization of
      hematomas was supratentorial, except for one patient who had both infratentorial
      and supratentorial hemorrhages. The mean National Institutes of Health score on
      admission was 15 and the Modified Rankin Scale score was higher than 4 at 3
      months. CONCLUSIONS: In our study, all patients with multiple SIHs had arterial
      hypertension and a poor outcome. Additional analytic studies, including new
      imaging techniques, can help to elucidate the association between arterial
      hypertension and multiple SIHs, risk factors, and underlying mechanisms of this
      clinical condition.

PMID- 11295995
TI  - Cluster analysis and patterns of findings on cranial magnetic resonance imaging
      of the elderly: the Cardiovascular Health Study.
AB  - OBJECTIVE: To characterize patterns of findings on cranial magnetic resonance
      imaging (MRI) of the elderly using a statistical technique called cluster
      analysis. SUBJECTS AND METHODS: The Cardiovascular Health Study is a population
      based, longitudinal study of 5888 people 65 years and older. Of these, 3230
      underwent cranial MRI scans, which were coded for presence of infarcts and grades
      for white matter, ventricles, and sulci. Cluster analysis separated participants
      into 5 clusters based solely on patterns of MRI findings. Participants comprising
      each cluster were contrasted with respect to cardiovascular risk factors and
      clinical manifestations. RESULTS: One cluster was low on all the MRI findings
      (normal) and another was high on all of them (complex infarcts). Another cluster
      had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters
      lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other
      having prominent white matter changes and enlarged ventricles (leukoaraiosis).
      Factors that distinguished these clusters in a discriminant analysis were age,
      sex, several measures of hypertension, internal carotid artery wall thickness,
      smoking, and prevalent claudication before the MRI. The atrophy group had the
      highest percentage of men and the normal group had the lowest. Cognitive and
      motor performance also differed across clusters, with the atrophy cluster
      performing better than may have been expected. CONCLUSIONS: These MRI patterns
      identified participants with different vascular disease risk factors and clinical
      manifestations. Results of these exploratory analyses warrant consideration in
      other populations of elderly people. Such patterns may provide clues about the
      pathophysiology of structural brain changes in the elderly.

PMID- 11295996
TI  - Cerebrovascular and brain morphologic correlates of mild cognitive impairment in
      the National Heart, Lung, and Blood Institute Twin Study.
AB  - OBJECTIVE: To evaluate the relative risk (RR) of mild cognitive impairment (MCI)
      associated with cerebrovascular risk factors and cerebrovascular-related brain
      changes. DESIGN: Mild cognitive impairment was determined for the subjects of the
      prospective National Heart, Lung, and Blood Institute Twin Study. Quantitative
      measures of brain, white matter hyperintensity, cerebral infarction,
      apolipoprotein E genotype, and psychometric testing were obtained. RESULTS:
      Subjects with MCI were older (73.5 +/- 3.0 vs 72.1 +/- 2.8 years), consumed less
      alcohol (3.7 +/- 5.8 vs 7.0 +/- 10.7 drinks per week), had greater white matter
      hyperintensity volumes (0.56% +/- 0.82% vs 0.25% +/- 0.34% of cranial volume),
      and had an increased prevalence of apolipoprotein E4 genotype (31.4% vs 19.2%)
      than normal subjects. White matter hyperintensity and the presence of the
      apolipoprotein E4 genotype were associated with a significantly increased risk
      for MCI. When all subjects were included in the analysis, alcohol consumption was
      associated with a reduced risk for MCI (RR = 0.93, P<.05). When subjects with a
      history of symptomatic cerebrovascular disease were excluded from the analysis,
      elevated midlife diastolic blood pressure was associated with an increased risk
      for MCI (RR = 1.70, P<.05). CONCLUSIONS: Elevated midlife blood pressures, and
      the resulting increased white matter hyperintensities, increase the risk for MCI
      in a group of community-dwelling older men to at least the same degree as
      apolipoprotein E4 genotype. Given the common occurrence of elevations in midlife
      blood pressure, early and effective treatment may be warranted to prevent late
      life brain abnormalities and MCI. Moreover, since many individuals with MCI
      progress to clinical dementia, longitudinal evaluations of this cohort will be
      important.

PMID- 11295997
TI  - Sensory dermatomal representation in the medial lemniscus.
AB  - BACKGROUND: Restricted sensory deficits along the somatotopic topography of the
      medial lemniscus rarely develop in medial medullary infarction. We describe a
      patient with medial medullary infarction who presented with dermatomal sensory
      deficits caused by a medial lemniscal lesion. CASE DESCRIPTION: A 58-year-old man
      presented with sudden right-sided hemiparesis and paresthesia. He had noticed the
      paresthesia below the level of the right L5 dermatome, where his vibration and
      position senses were mildly diminished. His paresthesia was more severe over the
      right calf and foot. Magnetic resonance images of the brain showed an acute small
      infarct in the medial-ventral portion of the left rostral medulla oblongata. A
      nerve conduction study and electromyography showed no abnormalities. At follow
      up, the patient's motor and sensory deficits had improved considerably.
      CONCLUSIONS: The patient showed lemniscal sensory deficits below the right L5
      dermatome that were caused by the partial involvement of the medial lemniscus.
      These findings suggest that lemniscal sensory dermatomal representation is
      preserved at least up to the level of the medulla oblongata.

PMID- 11295999
TI  - Towards visualization of symptomatic carotid stenosis.

PMID- 11295998
TI  - Convulsive-like movements in brainstem stroke.
AB  - BACKGROUND: Involuntary convulsive-like movements sometimes occur in patients
      with brainstem strokes. These movements vary in nature, frequency, and trigger,
      including fasciculation-like, shivering, jerky, tonic-clonic, and intermittent
      shaking movements. Some are interpreted as decerebrate postures or seizures. It
      is important to recognize this type of motor phenomenon since it may be a
      diagnostic clue for early diagnosis and treatment of brainstem strokes. DESIGN:
      Case report and review of the literature OBSERVATION: A 72-year-old-man presented
      with impaired consciousness and jerks of the upper limbs mimicking seizures.
      These episodes consisted of brief clonic contractions of the proximal and distal
      upper extremities. They were observed in paroxysms lasting for 3 to 5 seconds.
      Magnetic resonance imaging showed large midpontine infarction. Magnetic resonance
      angiography revealed the absence of basilar artery blood flow. No seizure
      discharges were observed in the electroencephalogram. Anticoagulation with
      intravenous heparin was started. Two days after admission, the patient had a
      cardiac arrest and died. We review the frequency and nature of convulsive-like
      movements in brainstem stroke in the literature. CONCLUSIONS: Movements
      associated with brainstem lesions are not easily differentiated from convulsions.
      Unexpected onset and inexperience of the observers limit the characterization of
      this phenomenon. Convulsive-like movements in brainstem stroke may occur more
      frequently than reported. Early detection of this motor phenomenon may have
      practical implications.

PMID- 11296000
TI  - Raeder syndrome.

PMID- 11296001
TI  - Neurology was there: 1910.

PMID- 11296002
TI  - Inflammation after stroke: is it harmful?

PMID- 11296003
TI  - Inflammation and stroke: benefits without harm?

PMID- 11296004
TI  - The potential for harm or benefit from inflammatory processes in stroke.

PMID- 11296005
TI  - Coexisting causes of ischemic stroke.

PMID- 11296006
TI  - Solitary inflammatory demyelination in the brain or spinal cord with tumor-like
      MRI presentations.

PMID- 11296007
TI  - The requirement for ictal EEG recordings prior to temporal lobe epilepsy surgery.

PMID- 11296009
TI  - Are demolition derby drivers a valid proxy for the population at risk for
      whiplash Injury?

PMID- 11296011
TI  - The DYT1 mutation and nonfamilial primary torsion dystonia.

PMID- 11296013
TI  - Endophthalmitis after keratoprosthesis: incidence, bacterial causes, and risk
      factors.
AB  - OBJECTIVES: To determine the rate of endophthalmitis in a group of patients with
      keratoprostheses and to analyze possible risk factors. METHODS: A total of 108
      patient eyes, operated on between 1990 and 2000 with double-plated
      keratoprostheses, were analyzed with regard to the surface flora, the incidence
      and cause of bacterial endophthalmitis or sterile vitreitis, the keratoprosthesis
      design, prophylactic antibiotics, concomitant immunosuppression, and preoperative
      diagnosis. RESULTS: Surveillance cultures were obtained from 30 uninfected eyes.
      The flora was similar to that reported in the normal population and did not vary
      significantly with time. Thirteen cases of bacterial endophthalmitis occurred 2
      to 46 months postoperatively in the patient population that had been followed up
      for 2 months to 17 years (average, 3 years 4 months). The incidence was 39% in 13
      patients with Stevens-Johnson syndrome, 19% in 27 patients with ocular
      cicatricial pemphigoid, and 7% in 28 patients with ocular burns. Only 1 of the
      other 40 cases (consisting mostly of repeated graft failures in noncicatrizing
      conditions) developed endophthalmitis; this patient had a filtering bleb. All
      endophthalmitis pathogens were gram positive: Streptococcus pneumoniae, 23%;
      other streptococci, 39%; Staphylococcus aureus, 23%; and Staphylococcus
      epidermidis, 15%. CONCLUSIONS: The most important risk factor for endophthalmitis
      after these keratoprostheses was found to be preoperative diagnosis. The rate of
      infection was very high in Stevens-Johnson syndrome and ocular cicatricial
      pemphigoid, moderate in chemical burns, and low in noncicatrizing corneal
      disease.

PMID- 11296014
TI  - Aqueous humor flow in normal human eyes treated with brimonidine and timolol,
      alone and in combination.
AB  - OBJECTIVE: To compare the effect on aqueous humor flow and intraocular pressure
      (IOP) of topically applied 0.2% brimonidine tartrate with topically administered
      0.5% timolol maleate, alone and in combination. DESIGN: A randomized, double
      masked, placebo-controlled study of 20 human subjects was carried out. The
      topical drugs were instilled twice daily the day before and again on the morning
      of the day of the measurements. Aqueous humor flow was measured by clearance of
      topically applied fluorescein with a fluorophotometer, and IOP was measured with
      an applanation tonometer. RESULTS: Brimonidine reduced the aqueous humor flow by
      33.1%; timolol, by 49.9%; and the combination of brimonidine and timolol, by
      58.9%. Brimonidine reduced the IOP by 20.3%; timolol, by 22.9%; and the
      combination of brimonidine and timolol, by 34.7%. CONCLUSIONS: Brimonidine
      suppressed aqueous humor flow, but not as effectively as timolol. However, the
      effects on the IOP of both drugs separately were comparable. The short-term
      effect of brimonidine was partly additive to timolol, and the combination
      treatment caused a further reduction in aqueous humor flow and IOP. The IOP
      reduction by timolol could be explained solely by aqueous humor flow reduction.
      Much of the IOP reduction caused by brimonidine, but not all, could be explained
      by suppression of the aqueous humor flow, suggesting an additional mechanism for
      the ocular hypotensive effect of brimonidine.

PMID- 11296015
TI  - The rod photoreceptors in retinopathy of prematurity: an electroretinographic
      study.
AB  - OBJECTIVE: To test the hypothesis that the more severe the acute phase
      retinopathy of prematurity (ROP) was in the preterm weeks, the more severely
      compromised is rod photoreceptor function after the ROP has resolved. METHODS:
      Electroretinographic (ERG) responses were recorded from 25 dark-adapted children
      (ages 2.5 months' postterm to 14 years) categorized by maximum, acute phase ROP
      (None to Very Severe). From the ERG a-wave "S," a sensitivity parameter for the
      rod photoreceptor response, and R(mp3), the saturated amplitude of the rod
      photoreceptor response were calculated using a model of the activation of rod
      phototransduction. The patients' results were compared with those of healthy
      controls (n = 71). RESULTS: Among those in the None, Mild, Moderate, and Severe
      categories, both S and R(mp3) varied significantly with severity of acute phase
      ROP. In the Very Severe category, ERG responses were too attenuated to calculate
      S and R(mp3). CONCLUSIONS: The rod photoreceptors must be involved in ROP. The
      more severe the acute phase ROP, the more severe is the compromise of the
      processes involved in the activation of phototransduction in the rods.

PMID- 11296016
TI  - Comparison of diagnosis of early retinal lesions of diabetic retinopathy between
      a computer system and human experts.
AB  - OBJECTIVE: To investigate whether a computer vision system is comparable with
      humans in detecting early retinal lesions of diabetic retinopathy using color
      fundus photographs. METHODS: A computer system has been developed using image
      processing and pattern recognition techniques to detect early lesions of diabetic
      retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool
      spots). Color fundus photographs obtained from American Indians in Oklahoma were
      used in developing and testing the system. A set of 369 color fundus slides were
      used to train the computer system using 3 diagnostic categories: lesions present,
      questionable, or absent (Y/Q/N). A different set of 428 slides were used to test
      and evaluate the system, and its diagnostic results were compared with those of 2
      human experts-the grader at the University of Wisconsin Fundus Photograph Reading
      Center (Madison) and a general ophthalmologist. The experiments included
      comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases
      excluded in the latter). RESULTS: In the training phase, the agreement rates,
      sensitivity, and specificity in detecting the 3 lesions between the retinal
      specialist and the computer system were all above 90%. The kappa statistics were
      high (0.75-0.97), indicating excellent agreement between the specialist and the
      computer system. In the testing phase, the results obtained between the computer
      system and human experts were consistent with those of the training phase, and
      they were comparable with those between the human experts. CONCLUSIONS: The
      performance of the computer vision system in diagnosing early retinal lesions was
      comparable with that of human experts. Therefore, this mobile, electronically
      easily accessible, and noninvasive computer system, could become a mass screening
      tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

PMID- 11296017
TI  - Spontaneous regression of optic gliomas: thirteen cases documented by serial
      neuroimaging.
AB  - OBJECTIVE: To demonstrate spontaneous regression of large, clinically symptomatic
      optic pathway gliomas in patients with and without neurofibromatosis type 1 (NF
      1). METHODS: Patient cases were collected through surveys at 2 consecutive annual
      meetings of the North American Neuro-Ophthalmology Society (NANOS) and through
      requests on the NANOSNET Internet listserv. Serial documentation of tumor signal
      and size, using magnetic resonance imaging in 11 patients and computed tomography
      in 2 patients, was used to evaluate clinically symptomatic optic pathway gliomas.
      All tumors met radiologic criteria for the diagnosis of glioma and 4 patients had
      biopsy confirmation of their tumors. In 3 patients, some attempt at therapy had
      been made many years before regression occurred. In one of these, radiation
      treatment had been given 19 years before tumor regression, while in another,
      chemotherapy had been administered 5 years before signal changes in the tumor. In
      the third patient, minimal surgical debulking was performed 1 year before the
      tumor began to shrink. RESULTS: Spontaneous tumor shrinkage was noted in 12
      patients. Eight patients did not have NF-1. In an additional patient without NF
      1, a signal change within the tumor without associated shrinkage was detected.
      Tumor regression was associated with improvement in visual function in 10 of 13
      patients, stability of function in 1, and deterioration in 2. CONCLUSIONS: Large,
      clinically symptomatic optic gliomas may undergo spontaneous regression.
      Regression was seen in patients with and without NF-1. Regression may manifest
      either as an overall shrinkage in tumor size, or as a signal change on magnetic
      resonance imaging. A variable degree of improvement in visual function may
      accompany regression. The possibility of spontaneous regression of an optic
      glioma should be considered in the planning of treatment of patients with these
      tumors.

PMID- 11296018
TI  - Absorption of 193- and 213-nm laser wavelengths in sodium chloride solution and
      balanced salt solution.
AB  - OBJECTIVE: To determine absorption coefficients for sodium chloride solution
      (saline) and balanced salt solution at the 193- and 213-nm laser wavelengths.
      METHODS: Absorption coefficients were obtained for each of the component species
      found in balanced salt solution. This was achieved by measuring laser pulse
      transmission through solutions of varying concentration. The experiments were
      repeated using the 193-nm excimer and 213-nm solid-state laser wavelengths.
      Results for each species were then used to obtain an overall absorption
      coefficient and penetration depth for balanced salt solution and 0.9% sodium
      chloride solution. RESULTS: Absorption coefficients in balanced salt solution for
      the 193- and 213-nm wavelengths were found to be 140 and 6.9 cm(-1),
      respectively. In 0.9% sodium chloride solution, the absorption coefficient was 81
      cm(-1) at 193 nm and 0.05 cm(-1) at 213 nm. At 193 nm, absorption in balanced
      salt solution was dominated by sodium chloride. Sodium citrate emerged as the
      dominant species of absorption at 213 nm. CONCLUSIONS: For the species
      investigated, we found reduced absorption for the longer wavelength of 213 nm.
      While the difference in wavelength between 193 and 213 nm is within about 10%,
      the respective molar absorption coefficients varied by 1 to 4 orders of
      magnitude. This indicates that predictions for the wavelength-dependent changes
      of absorption coefficients of other solutions are unreliable. CLINICAL RELEVANCE:
      Fluid placed on the surface of the cornea during keratorefractive surgery has
      proved to be a barrier to ablation for the 193-nm wavelength. The increased
      penetration depth through sodium chloride solution and balanced salt solution for
      the longer 213-nm laser wavelength may mean that these solutions cannot be used
      as a masking agent for keratorefractive procedures performed with this
      wavelength.

PMID- 11296019
TI  - Hydraulic conductivity of fixed retinal tissue after sequential excimer laser
      ablation: barriers limiting fluid distribution and implications for cystoid
      macular edema.
AB  - OBJECTIVES: To measure the hydraulic conductivity (HC) of human retina and to
      determine the presence and location of high-resistance barriers to fluid movement
      through the retina. METHODS: Forty-one pairs of human eyes were investigated
      using an HC chamber. Once baseline HC had been determined, the effect of ablating
      through varying thickness of retina from the vitreous or photoreceptor surface
      using an excimer laser (193 nm) was investigated. Tissue samples were then
      processed for histological investigation. RESULTS: The HC of fixed intact human
      retina was 2.54 x 10(-10) m/s per pascal at 539 Pa (range, 0.6 x 10(-10) to 3.3 x
      10(-10) m/s per pascal; SD, 0.6 x 10(-10) m/s per pascal [1 mm Hg equals 133
      Pa]). Ablation from either surface resulted in little change in HC until a
      critical depth was reached, at which point there was an order of magnitude
      increase. The critical depth was approximately 170 microm from the inner limiting
      membrane when ablating from the vitreous surface and 70 microm from the inner
      limiting membrane when ablating from the photoreceptor surface. Histological
      specimens showed that these barriers were the synaptic portion of the outer
      plexiform layer, and the inner plexiform layer, respectively. CONCLUSIONS: The 2
      high-resistance barriers to fluid flow through the retina are the synaptic
      portion of the outer plexiform layer, and the inner plexiform layer. CLINICAL
      RELEVANCE: These observations help to explain the distribution of cystoid macular
      edema seen in histological studies and with optical coherence tomography.

PMID- 11296020
TI  - How many steps of progression of diabetic retinopathy are meaningful? The
      Wisconsin epidemiologic study of diabetic retinopathy.
AB  - OBJECTIVE: To determine whether a 1-step or more or 2-step or more progression on
      the Early Treatment Diabetic Retinopathy Study retinopathy severity scale over a
      4-year period is meaningful in predicting the subsequent incidence of
      proliferative diabetic retinopathy (PDR) and clinically significant macular edema
      (CSME) over the following 6 years. DESIGN: Population-based study of diabetic
      persons with 10 years of follow-up. SETTING AND PATIENTS: Eleven-county area in
      southern Wisconsin. There were 1025 persons with diabetes who had fundus
      photographs at baseline and at 4- and 10-year follow-up examinations. MAIN
      OUTCOME MEASURES: Incidence of PDR or CSME between the 4- and 10-year follow-up
      examinations as determined by masked grading of color stereoscopic fundus
      photographs of 7 standard fields. RESULTS: In a univariate analysis, those with 1
      or more steps of progression (n = 551) over the first 4 years of the study were
      significantly (P<.0001) more likely to develop PDR over the next 6 years than
      those with no progression (n = 474) (26% vs 4%) (relative risk, 5.85; 95%
      confidence interval, 4.05-8.47). Similarly, those with 2 or more (n = 364) (33%)
      or 3 or more (n = 231) (41%) steps of progression over the first 4 years of the
      study were significantly (P<.0001) more likely to develop PDR over the next 6
      years than those with lesser progression (n = 661 [7%] and n = 794 [9%],
      respectively) (relative risk, 5.10; 95% confidence interval, 3.83-6.80; and
      relative risk, 4.61; 95% confidence interval, 3.57-5.99, respectively). Similar
      associations were apparent at every level of retinopathy, duration of diabetes,
      and glycosylated hemoglobin, and by type of diabetes at baseline. There were also
      associations between retinopathy progression and incidence of CSME. CONCLUSIONS:
      It seems that 1 or more or 2 or more steps of progression of retinopathy over a 4
      year period strongly predict the development of PDR over the next 6 years.
      Therefore, using these end points of progression would result in the need for
      fewer subjects or shorter follow-up in some clinical trials.

PMID- 11296021
TI  - Photographic measures of cytomegalovirus retinitis as surrogates for visual
      outcomes in treated patients.
AB  - OBJECTIVE: To evaluate photographic measures of cytomegalovirus (CMV) retinitis
      as surrogate outcomes for changes in vision in patients with CMV retinitis
      related to the acquired immunodeficiency syndrome. METHODS: Data from 3 clinical
      trials of CMV retinitis treatments were analyzed. Two photographic assessments of
      retinitis in eyes involved at baseline were evaluated: progression (lesion border
      movement > or = 750 microm or occurrence of a new lesion) and change in area of
      retina involved with retinitis. Vision measures were decline in best-corrected
      visual acuity and change in visual field. Photographic measures were evaluated as
      surrogate outcomes based on 4 criteria: (1) association with vision measure; (2)
      ability to account for treatment-related differences in vision measure; (3) data
      completeness; and (4) sample size requirements. RESULTS: Data from 1001 involved
      eyes (666 patients) were analyzed. Progression and change in area involved were
      predictive of declines in vision measures, accounted for 50% and 66% of the
      treatment effect on visual field, and were available from 93% and 64% of involved
      eyes, respectively. Sample size estimates for a clinical trial were smallest with
      progression as the design outcome. CONCLUSION: Progression and change in area
      involved met the first and second criteria for surrogate outcomes for visual
      field loss; a complete evaluation for visual acuity decline was not possible
      because treatment-related differences were not observed. Progression met the
      logistical and sample size criteria better than change in area of retina involved
      with retinitis.

PMID- 11296022
TI  - Autosomal dominant Stargardt-like macular dystrophy: founder effect and
      reassessment of genetic heterogeneity.
AB  - OBJECTIVES: To characterize a disease-associated haplotype in 7 families with
      autosomal dominant Stargardt-like macular dystrophy and to determine whether
      these families share a common ancestor. METHODS: Twenty-five polymorphic DNA
      markers spanning known dominant Stargardt-like gene loci were used to determine
      the haplotype associated with disease. In addition, an extensive genealogical
      investigation searching for a common ancestor shared by all of the 7 families was
      performed. RESULTS: We clinically evaluated 171 patients and genotyped 145
      samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated
      affected members within the 7 families. In addition, we were able to
      genealogically join all of the families into one larger family consisting of 31
      branches and 2314 individuals. Twenty-seven branches have known living
      descendants, with 7 branches having affected family members. In addition, we
      refined the critical region for the gene to approximately 1000 kilobases (kb) and
      eliminated part or all of 9 candidate disease-causing genes. CONCLUSIONS: Our
      study indicates that most reported cases of autosomal dominant Stargardt-like
      macular dystrophy in North America are part of a single larger family associated
      with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated
      with disease is useful in excluding individuals with phenotypically similar
      retinal conditions. CLINICAL RELEVANCE: The disease-associated haplotype allows
      for more accurate genetic counseling to be given to individuals with a Stargardt
      like phenotype inherited in an autosomal dominant pattern.

PMID- 11296023
TI  - Once again high tech meets low tech on chromosome 6.

PMID- 11296024
TI  - Surrogate outcomes for clinical trials: use with caution.

PMID- 11296025
TI  - Newly recognized complications of posterior chamber intraocular lenses.

PMID- 11296026
TI  - Evidence-guided ophthalmology.

PMID- 11296027
TI  - Considerations for choosing an electronic medical record for an ophthalmology
      practice.
AB  - OBJECTIVES: To give a brief overview of issues pertinent to selecting an
      ophthalmic electronic medical record (EMR) program and to outline the company
      demographics and software capabilities of the major vendors in this area.
      METHODS: Software companies shipping an EMR package were contacted to obtain
      information on their software and company demographics. The focus was on
      companies selectively marketing to ophthalmology practices, and, therefore, most
      were selected based on their representation at the 1998 and/or 1999 American
      Academy of Ophthalmology meeting. Software companies that responded to repeated
      inquiries in a timely fashion were included. RESULTS: Sixteen companies were
      evaluated. Electronic medical records packages ranged from $3000 to $80 000
      (mean, approximately $30 000). Company demographics revealed a range from 1 to
      1600 employees (mean, 204). Most of these companies have been in business for 6
      years or less (range, 1-15 years; mean, 6 years). My opinions concerning various
      aspects of the EMR are presented. CONCLUSIONS: There is a wide range of EMR
      products available for the ophthalmology practice. Computer technology has
      matured to a point at which the graphical demands of the ophthalmology EMR can be
      satisfied. Weaknesses do exist in the inherent difficulty of recording an
      ophthalmology encounter, the relative adolescence of software companies, and the
      lack of standards in the industry.

PMID- 11296028
TI  - Adenocarcinoma arising from congenital hypertrophy of retinal pigment epithelium.
AB  - Congenital hypertrophy of the retinal pigment epithelium (CHRPE), traditionally
      regarded as a benign stationary condition, has recently been shown in 5 cases to
      give rise to an elevated, solid tumor. However, the histopathologic nature of the
      tumor that arises from CHRPE has not been previously determined. A 65-year-old
      woman developed a progressively enlarging peripheral fundus tumor that arose from
      a focus of classic CHRPE. The tumor produced a localized exudative retinal
      detachment, cystoid macular edema, and surface-wrinkling retinopathy. The mass
      was removed by local resection, and histopathologic examination revealed a low
      grade adenocarcinoma of the retinal pigment epithelium, apparently arising from
      CHRPE. Although CHRPE is usually a benign nonprogressive lesion, it can give rise
      to a malignant tumor. Congenital hypertrophy of the retinal pigment epithelium
      should be observed periodically for development of a neoplasm.

PMID- 11296029
TI  - Sclerosing inflammatory pseudotumor of the eye.
AB  - We report the clinical course and pathologic findings in a case of intraocular
      sclerosing inflammatory pseudotumor in a 21-year-old man. The patient initially
      had a unilateral right interstitial keratitis, scleritis, uveitis, ciliary body
      mass, and retinal detachment. Scleral and vitreous biopsy specimens revealed an
      inflammatory process. The eye was eventually enucleated despite therapy with high
      doses of prednisone and ciprofloxacin hydrochloride. Histologic examination of
      the globe showed nongranulomatous, acute (neutrophils) and chronic (lymphocytes
      and histiocytes) inflammation with proliferation of fibrous tissue within the
      vitreous cavity, uvea, sclera, and contiguous orbital fibroadipose tissue. The
      contralateral eye later developed a similar mass that resolved following
      aggressive and prolonged immunosuppressive therapy with retention of 20/16 visual
      acuity.

PMID- 11296030
TI  - Optic chiasm, optic nerve, and retinal involvement secondary to varicella-zoster
      virus.
AB  - Immunocompromised patients are known to be at risk for varicella-zoster virus
      reactivation, often in atypical manners. We describe a 30-year-old man with
      simultaneous involvement of the retina, optic chiasm, and optic nerve with
      varicella-zoster virus who had a bitemporal visual field defect.

PMID- 11296031
TI  - Hydroxyapatite formation on implanted hydrogel intraocular lenses.

PMID- 11296032
TI  - Latanoprost and periocular skin color changes.

PMID- 11296033
TI  - Iris atrophy, cataracts, and hypotony following peripheral ablation for threshold
      retinopathy of prematurity.

PMID- 11296034
TI  - Primary intraocular lymphoma seen with transient white fundus lesions simulating
      the multiple evanescent white dot syndrome.

PMID- 11296035
TI  - Factors in the prevention of wound dehiscence during pneumatic retinopexy.

PMID- 11296037
TI  - Fluorescein angiograms do not support choroidal ischemia.

PMID- 11296039
TI  - Submission of data sets to journals: opportunities for improving good research
      practice.

PMID- 11296040
TI  - Posterior polymorphous membranous dystrophy with overlapping features of
      iridocorneal endothelial syndrome.

PMID- 11296041
TI  - Periventricular leukomalacia: an intracranial cause of pseudoglaucomatous
      cupping.

PMID- 11296042
TI  - Pediatric cochlear implantation: the parents' perspective.
AB  - OBJECTIVE: To analyze parental views on cochlear implantation, before and in the
      years following implantation, to determine whether the results from the
      intervention met their expectations. DESIGN: Prospective longitudinal study to
      assess parental perspectives of an unselected group of children with cochlear
      implantation. SETTING: Tertiary referral pediatric cochlear implant center in the
      United Kingdom. SUBJECTS: Forty-three parents of children with cochlear
      implantation. INTERVENTION: A specifically designed questionnaire was
      administered to assess preimplant expectations and observed changes and concerns
      at 1, 2, and 3 years following implantation. Three key domains were evaluated:
      (1) communication with others, (2) listening to speech without lipreading, and
      (3) the development of speech and language. RESULTS: Preoperative expectations
      were met or surpassed at each of the follow-up intervals. In the area of
      communication, 35 (81%) parents expected a definite improvement preoperatively,
      and 3 years following implantation, 42 (98%) actually saw such an improvement.
      The respective numbers in the area of listening to speech were 15 (35%) and 38
      (88%), and for speech development, 37 (86%) and 37 (86%). Speech development was
      the major area of concern at all intervals. CONCLUSION: This study demonstrates
      the ability of cochlear implantation to meet or surpass parental expectations in
      3 important outcome domains: communication, listening to speech, and the
      development of speech and language.

PMID- 11296043
TI  - Correlation of findings at direct laryngoscopy and bronchoscopy with
      gastroesophageal reflux disease in children: a prospective study.
AB  - OBJECTIVE: To correlate direct laryngoscopic and bronchoscopic findings with the
      presence of positive test results for gastroesophageal reflux disease (GERD) in
      children. DESIGN: Prospective collection of structured data. SETTING: An academic
      pediatric otolaryngology department. PATIENTS: Seventy-seven consecutive patients
      who underwent direct laryngoscopy and bronchoscopy between June and October 1999.
      INTERVENTIONS: During direct laryngoscopy and bronchoscopy, descriptions of 7
      laryngeal and 6 cricotracheal findings were recorded on a 3-point scale (i.e.,
      absent, mild, or severe). Medical records were later reviewed to obtain results
      of the following tests, if they were part of the record: gastric scintiscan, 24
      hour pH probe monitoring, upper gastrointestinal tract series, and esophageal
      biopsy. MAIN OUTCOME MEASURES: Correlation of mucosal abnormalities with the
      presence or absence of a positive test result for GERD. RESULTS: Fifty (65%) of
      77 patients had GERD diagnosed with at least 1 positive test result, 21 (27%) had
      no clinical symptoms and no positive GERD test results, and 5 (7%) had clinical
      symptoms but no positive test results. There were significant differences for
      total laryngeal and cricotracheal scores (P<.001) between the groups with
      positive and negative results. Significant differences were as follows: in the
      larynx-large lingual tonsil (P<.001), postglottic edema (P<.001), arytenoid edema
      (P<.001), ventricle obliteration (P =.03), and true vocal fold edema (P = .001),
      and in the cricotracheal region-general edema and erythema (P =.003) and blunting
      of the carina (P<.001). Severe arytenoid edema, postglottic edema, or enlargement
      of lingual tonsil were pathognomonic of GERD. CONCLUSION: Many direct
      laryngoscopic and bronchoscopic findings correlate well with the diagnosis of
      GERD as determined by using other tests.

PMID- 11296044
TI  - Etiology and management of pediatric hemoptysis.
AB  - OBJECTIVE: To review the diagnostic and treatment strategies of hemoptysis in
      children. DESIGN: Retrospective analysis of patients evaluated between January 1,
      1995, and August 31, 1999. SETTING: Tertiary pediatric referral center. PATIENTS:
      Nineteen consecutive children presenting with hemoptysis to the otolaryngology
      service. RESULTS: Chest radiography and bronchoscopy established the correct
      etiology in 15 patients. Infection and tracheostomy-related complications were
      the most common underlying problems. Other causes included congenital heart
      disease, pulmonary hemosiderosis, inflammatory bronchial mass, cystic fibrosis,
      factitious hemoptysis, and esophagitis. Appropriate management, ranging from
      antibiotics to emergency embolization, resulted in control of hemoptysis in all
      patients. CONCLUSIONS: Hemoptysis is a rare but potentially life-threatening
      symptom of underlying respiratory tract abnormality in children. An efficient
      systematic evaluation is imperative to identifying the underlying etiology;
      aggressive management is important because of the potential severity of the
      problem. The otolaryngologist plays a pivotal role in the diagnosis and
      management, by flexible endoscopy of the nose, nasopharynx, and larynx, and
      through the use of rigid bronchoscopy, especially in cases of massive hemoptysis.

PMID- 11296045
TI  - Tramadol vs. diclofenac for posttonsillectomy analgesia.
AB  - OBJECTIVE: To compare the analgesic efficacy of oral tramadol hydrochloride and
      oral diclofenac sodium for posttonsillectomy pain management. DESIGN: Single
      blind (surgeon and research team members), prospective, randomized, controlled
      clinical trial. PATIENTS AND METHODS: Sixty-four patients 11 years and older
      undergoing bipolar electrocautery tonsillectomy were randomized to either the
      oral tramadol or the oral diclofenac postoperative pain group. Patients recorded
      pain levels twice daily for 14 days using a visual analogue scale. RESULTS: Pain
      scores for the 14 days were not significantly different between the oral tramadol
      and oral diclofenac groups. There were no significant differences in the
      incidence of postoperative hemorrhage and hospital readmission for uncontrolled
      pain. CONCLUSION: Oral tramadol can deliver the same analgesic efficacy as oral
      diclofenac for posttonsillectomy pain relief, which might be beneficial for
      avoiding the adverse effects of nonsteroidal anti-inflammatory drug therapy.

PMID- 11296046
TI  - Impact on quality of life of botulinum toxin treatments for spasmodic dysphonia
      and oromandibular dystonia.
AB  - OBJECTIVE: To determine the impact on quality of life of botulinum toxin
      treatments for common dystonias of the head and neck. DESIGN: Cross-sectional
      survey study of a patient cohort treated with botulinum toxin injections for
      spasmodic dysphonia (SD) or oromandibular dystonia (OMD). INTERVENTIONS AND
      OUTCOME MEASURES: The Glasgow Benefit Inventory was used to quantify the health
      benefit of treatment. Data were collected for demographics, time intervals
      relative to diagnosis, treatment duration, and frequency of injections. The
      groups were compared to determine whether differences existed in benefit from
      treatment. Correlation analysis was conducted for inventory scores and time
      intervals. RESULTS: A total of 23 patients (5 with OMD and 18 with SD) completed
      the questionnaire. The mean total benefit score was +38.04 (possible range, -100
      to +100) for the whole group (P<.001). The OMD group derived a nonsignificantly
      smaller benefit (+21.67 vs +42.59) (P =.07). The mean subscores for the combined
      group were +39.67, +26.81, and +42.75 for the general, social support, and
      physical health subscores, respectively (P< or =.001). The difference in mean
      subscores between the 2 groups was not statistically significant, although
      patients with OMD had a lower social support subscore (+6.67 vs. +32.41). No
      correlation was found between duration of therapy or frequency of injections and
      the Glasgow Benefit Inventory score. CONCLUSIONS: Patients with OMD or SD derive
      considerable benefit when treated with botulinum toxin. The magnitude of benefit
      is largely independent of the time course of therapy. Treatment with botulinum
      toxin for these conditions is effective on the basis of quality-of-life criteria.

PMID- 11296047
TI  - Long-term therapy for spasmodic dysphonia: acoustic and aerodynamic outcomes.
AB  - OBJECTIVE: To evaluate the long-term aerodynamic, acoustic, and electromyographic
      effects of serial botulinum toxin (BT) injections in patients with adductor
      spasmodic dysphonia. DESIGN: Two-year, nonrandomized, controlled, before-after
      study. SETTING: Ambulatory care clinic at a single academic medical center.
      PATIENTS: A convenience sample of 91 patients with adductor spasmodic dysphonia
      evaluated and treated during 2 years and 64 age- and sex-matched controls.
      INTERVENTIONS: Injections of BT into the thyroarytenoid muscles in conjunction
      with electromyographic evaluation and acoustic and aerodynamic evaluation before
      and after serial BT injections. MAIN OUTCOME MEASURES: Translaryngeal airflow,
      jitter, shimmer, signal-to-noise ratio, fundamental frequency, standard deviation
      of fundamental frequency, maximum phonation time, and inappropriate muscle
      activity by electromyography. RESULTS: Translaryngeal airflow, jitter, and
      shimmer improved significantly after serial BT treatments and showed sustained
      improvement over time. Fundamental frequency, standard deviation of fundamental
      frequency, and signal-to-noise ratio did not change significantly after BT
      treatment. Electromyographic data suggested decreased inappropriate muscle
      activity with repeated BT injections. CONCLUSION: Treatment with BT provides
      ongoing relief of voice perturbations in patients with adductor spasmodic
      dysphonia who undergo long-term cumulative therapy.

PMID- 11296048
TI  - Secondary otalgia in an adult population.
AB  - OBJECTIVE: To analyze the associations of secondary otalgia with general health,
      stress, insomnia, bruxism, and recurrent head and neck region pains. DESIGN: A
      population-based survey. SETTING: General community. SUBJECTS: A total of 391
      randomly selected subjects (186 men, 205 women) aged 25, 35, 45, 55, or 65 years.
      METHODS: Standardized interview and self-report questionnaires of general health
      and stress. RESULTS: Otalgia was statistically significantly associated with all
      the studied factors. However, in the whole study group, independent predictors of
      otalgia were the obvious need for temporomandibular disorder treatment, high
      frequency of stress symptoms, and bruxism. When analyzed in women, the predictors
      of otalgia were the obvious need for temporomandibular disorder treatment, high
      frequency of stress symptoms, and age. When analyzed in men, recurrent neck pain
      was a predictor of otalgia. CONCLUSIONS: We suggest that after ruling out
      otorhinolaryngologic infectious diseases and temporomandibular disorder in
      patients with secondary otalgia, the next step is to explore the frequency of
      stress symptoms, bruxism, and recurrent neck pain. Furthermore, women and men may
      need a different approach in diagnostics of secondary otalgia. By diagnosing and
      treating these predictors of otalgia, it may be possible to reach a more
      successful outcome.

PMID- 11296049
TI  - Occult primary tumors of the head and neck: accuracy of thallium 201 single
      photon emission computed tomography and computed tomography and/or magnetic
      resonance imaging.
AB  - OBJECTIVE: To determine the accuracy of thallium 201 single-photon emission
      computed tomography (thallium SPECT) and computed tomography and/or magnetic
      resonance imaging (CT/MRI) in the detection of occult primary tumors of the head
      and neck. DESIGN: Study of diagnostic tests. SETTING: National Cancer Institute,
      Amsterdam, the Netherlands. PATIENTS AND METHODS: Thirty-two patients with a neck
      node metastasis of an epithelial tumor and negative findings by mirror
      examination at initial presentation were included in the study. Twenty-nine
      patients underwent thallium SPECT and CT/MRI before examination under general
      anesthesia (EUA). In 3 patients only thallium SPECT was performed before EUA.
      Histological confirmation of an occult primary tumor during EUA was used as the
      gold standard. Negative radiodiagnostic and nuclear findings in the upper
      aerodigestive tract in the presence of a primary carcinoma other than of the head
      and neck were interpreted as true-negative findings. RESULTS: For thallium SPECT
      the following results were recorded: sensitivity, 67%; specificity, 69%;
      accuracy, 69%; positive predictive value, 33%; and negative predictive value,
      90%. In 1 patient, thallium whole body scan indicated a primary carcinoma beyond
      the mucosal lining of the upper aerodigestive tract. The CT/MRI results were as
      follows: sensitivity, 71%; specificity, 73%; accuracy, 72%; positive predictive
      value, 45%; and negative predictive value, 89%. CONCLUSIONS: Thallium SPECT and
      CT/MRI showed comparable results for detection of occult primary tumors of the
      head and neck. A potential advantage of thallium SPECT is that it allows total
      body screening.

PMID- 11296050
TI  - Laser-assisted uvulopalatoplasty for snoring: medium- to long-term subjective and
      objective analysis.
AB  - OBJECTIVE: To assess the subjective and objective medium- to long-term results of
      laser-assisted uvulopalatoplasty for snoring. DESIGN: A nonrandomized,
      prospective, before-after trial. SUBJECTS AND INTERVENTIONS: Fourteen patients
      underwent laser-assisted uvulopalatoplasty surgery; 2 surgical techniques, which
      differ with respect to the mode of midline palatal vaporization, were used. MAIN
      OUTCOME MEASURES: Subjective analysis included a preoperative and 2 postoperative
      evaluations of the state of snoring: 4 weeks and 10.1 +/- 7.9 months (mean +/-
      SD) after completion of last laser treatment. In addition, a score on 5 other
      sleep-related symptoms was recorded before treatment and after 10.1 +/- 7.9
      months; at that time, patients also estimated their overall satisfaction with the
      procedure. Objective analysis included preoperative nocturnal polysomnographic
      studies that were repeated postoperatively. RESULTS: A decline in snoring
      improvement from 79% (11/14) to 57% (8/14) was recorded; furthermore, state of
      snoring worsened from 7% (1/14) to 21% (3/14). Likewise, reevaluation of the 5
      other sleep-related symptoms at the final follow-up visit uncovered a 57%
      improvement rate. Overall satisfaction with the procedure was 43%. The results of
      the postoperative objective studies corresponded to those of the subjective ones
      and demonstrated significant worsening of respiratory disturbance index in 3
      (21%) of the 14 patients, who became mildly apneic. These findings were
      encountered with both laser techniques. CONCLUSIONS: The favorable subjective
      short-term results of laser-assisted uvulopalatoplasty deteriorated with time. In
      addition, postoperative nocturnal polysomnography showed that the procedure
      caused mild obstructive sleep apnea in a considerable number of patients who
      formerly were nonapneic snorers. These findings may be related to velopharyngeal
      narrowing and progressive palatal fibrosis, caused by the thermal damage
      inflicted by the laser beam.

PMID- 11296051
TI  - Laser resurfacing of silicone-injected skin: the "silicone flash" revisited.
AB  - OBJECTIVE: To determine whether prior silicone injection increases the risks
      associated with carbon dioxide laser resurfacing. DESIGN: Laboratory
      determination of the effect of laser energy on liquid silicone; histologic
      evaluation of silicone-injected skin after lasing; and histologic demonstration
      of silicone deposits in all layers of dermis years after injection of silicone as
      filler fluid. SETTING: Tertiary care medical center. PATIENT-RELATED DATA:
      Histologic examination of freshly excised skin injected with microdroplets of
      liquid silicone and subjected to application of carbon dioxide laser energy;
      histologic examination of skin excised years after silicone injection.
      INTERVENTIONS: High-speed clinical photographic imaging of the effect of laser
      energy on silicone fluid; histologic examination of hematoxylin-eosin-stained
      sections of skin injected with liquid silicone and subsequently lased. MAIN
      OUTCOME MEASURES: Response of liquid silicone to application of laser energy;
      effect of this response on surrounding normal skin. RESULTS: Exposure of
      microdroplets of liquid silicone to carbon dioxide laser energy produced flaring
      with frank flame. Flaring of dermal silicone caused collateral skin damage.
      CONCLUSIONS: Prior injection with liquid silicone is a relative contraindication
      to cutaneous resurfacing with the carbon dioxide laser. Surgical excision of
      silicone-injected skin may be preferable for many patients. A strenuous needs
      assessment should be done, alternatives for skin rejuvenation considered, and
      comprehensive informed consent obtained from the patient before embarking on
      laser resurfacing of silicone-injected skin.

PMID- 11296052
TI  - Experimental study on facial nerve regeneration with or without geniculate
      ganglionectomy.
AB  - OBJECTIVE: To investigate regeneration of the distal facial nerve following nerve
      grafting within the tympanic segment with geniculate ganglion preservation or
      dissection. DESIGN: Randomized controlled trial. SUBJECTS: Twenty-three adult New
      Zealand albino rabbits were used in this study. INTERVENTIONS: A 2-mm tympanic
      segment of the facial nerve was removed, and the greater auricular nerve was
      harvested for grafting in all animals. In group 1 (10 rabbits), the geniculate
      ganglion was preserved. In group 2 (13 rabbits), the geniculate ganglion was
      dissected. Mastoidal and extratemporal segments of the facial nerve were
      harvested 3 months postoperatively for histological examination by electron
      microscopy. RESULTS: The number of myelinated axons in normal facial nerves was
      1819.6 +/- 535.6. In group 1, the number of myelinated axons was 123.6 +/- 31.1,
      and, compared with normal facial nerves, the diameter of the regenerative axons
      was decreased and the sheath thickness in the regenerative fiber was diminished.
      In group 2, the number of myelinated axons was 515.1 +/- 103.1, while the myelin
      sheath thickness was proportionate to axon diameter. (Data are given as mean +/-
      SD.) CONCLUSION: Geniculate ganglionectomy may improve motor axon regeneration.

PMID- 11296053
TI  - Growth and development of homograft tracheal transplants in the piglet model.
AB  - OBJECTIVE: To determine the growth characteristics of homograft tracheal
      transplants in piglets. DESIGN: Prospective controlled animal study. SETTING:
      Clinical animal laboratory. SUBJECTS: Seventeen Yorkshire swine piglets.
      INTERVENTIONS: The tracheae of adult Yorkshire swine were harvested and treated
      with formaldehyde, thimerosal, and acetone to remove immunogenic major
      histocompatibility complexes. Eleven piglets had these chemically treated
      homografts transplanted into 6-cm surgically created tracheal defects. The
      transplants were stented. Three control piglets had a 6-cm anterior
      tracheofissure, no transplant, and surgical placement of the stent. Three other
      control piglets had no transplant, and the stent was placed endoscopically. MAIN
      OUTCOME MEASURES: Growth outcome measurements were tracheal length and diameter.
      Functional outcome measurements were lumen patency and graft viability indicated
      by cartilage retention. RESULTS: The mean diameter of the tracheae in the stented
      tracheal transplant group was 11.7 mm before transplantation and 6.6 mm 2 months
      after transplantation. The transplanted segments were significantly malacic 2
      months after transplantation. The mean diameter of the tracheae in the
      tracheofissure group was 9.0 mm before surgery and 11.0 mm 2 months after
      surgery. The mean diameter of the tracheae in the endoscopically stented group
      was 11.0 mm before surgery and 14.0 mm 2 months after stent placement. All
      homografts showed evidence of extensive resorption of the graft cartilage. The
      graft cartilage was replaced by collagen, with minimal evidence of
      neochondrification. There was no evidence of host-vs-graft rejection. All grafted
      trachea had severe tracheomalacia with granulation tissue. CONCLUSIONS: Homograft
      tracheal transplantation results in a tracheal segment that is replaced with
      collagen. The transplanted cartilage is resorbed, leaving a significantly malacic
      segment. Homograft tracheal transplantation might result in a small malacic
      airway with little potential for growth when performed in children.

PMID- 11296054
TI  - Transoral removal of submandibular stones.
AB  - OBJECTIVE: To assess transoral treatment of submandibular lithiasis. DESIGN:
      Study of a series of patients with submandibular stones undergoing transoral
      removal of the sialoliths. Duration of follow-up: 6 months to 7 years. SETTING:
      Department of Otorhinolaryngology, Head and Neck Surgery, University of Erlangen
      Nuremberg, Erlangen, Germany, center for treatment of salivary stones. PATIENTS:
      Two hundred thirty-one patients (127 females, 104 males) suffering from
      submandibular lithiasis had a mean age of 41.7 years (age range, 12-86 years).
      Stone location was distal to the edge of the mylohyoid muscle in 115 patients and
      proximal to the gland in 102 patients (mean size of sialoliths, 6.3 mm [range, 2
      30 mm]). Fourteen other patients had 2 separate stones, one within the hilum and
      a smaller more proximal one within the gland. INTERVENTIONS: Transoral removal of
      the stones under local anesthesia and preservation of the submandibular gland.
      MAIN OUTCOME MEASURES: Complete removal of the stones, complications, and
      recurrence of the stones. RESULTS: All 115 patients with distal stone location,
      93 (91%) of 102 patients with stones of the perihilar region, and 9 (64%) of the
      14 patients with 2 separate stones in the hilum and parenchyma were free of
      stones. Submandibulectomy had to be carried out in 4 patients (1.7%). Recurrence
      of lithiasis and damage to the lingual nerve remained below 1%. CONCLUSIONS:
      Transoral removal should be the treatment of choice in patients with
      submandibular stones that can be palpated bimanually and localized by ultrasound
      within the perihilar region of the gland.

PMID- 11296055
TI  - Graft-vs-host disease as a cause of enlargement of the epiglottis in an
      immunocompromised child.
AB  - We report a rare case of dyspnea due to enlargement of the epiglottis in a
      severely immunocompromised patient. The child underwent a previous tracheostomy
      at another hospital because of respiratory distress under the diagnosis of acute
      epiglottitis. The patient was subsequently decannulated without incident. One
      year later, the child developed a new episode of dyspnea with inspiratory
      stridor. A new tracheostomy was neccessary, and a biopsy specimen of the enlarged
      epiglottis was taken to confirm the diagnosis of graft-vs-host disease. The
      therapeutic measures in these situations are discussed below, and a review of the
      current literature concerning the etiology and management of epiglottic
      enlargement is performed.

PMID- 11296056
TI  - Latex allergy: an update for the otolaryngologist.
AB  - OBJECTIVE: To describe the clinical manifestations of latex allergy in
      otolaryngology patients. DESIGN: Descriptive case series. SETTING: Tertiary
      academic otolaryngology practice. PATIENTS: Otolaryngology patients with
      documented allergic reactions to latex during surgery and confirmatory laboratory
      test results for latex allergy. MAIN OUTCOME MEASURES: Clinical description of
      latex reactions; identification of risk factors for latex allergy. RESULTS: We
      describe 3 patients, 2 children and 1 young adult, with severe latex allergy
      manifested by intraoperative cardiorespiratory changes and confirmed by positive
      latex-specific IgE test results. A 9-year-old boy with a tracheotomy and a
      history of multiple procedures for laryngeal stenosis developed a rash and
      unexplained bronchospasm during an open laryngeal procedure. Surgery was aborted,
      and subsequent surgery was performed uneventfully 4 weeks later using a latex
      safe environment. A 13-year-old boy with recurrent respiratory papillomatosis and
      a ventriculoperitoneal shunt had sudden unexplained arterial oxygen desaturation
      and a rash during laser endoscopy. He was then treated successfully using latex
      safe protocols. A 23-year-old man with a parotid malignancy developed unexplained
      hypotension and ventilatory difficulties in the operating room during preparation
      for surgery. He responded to medical treatment for anaphylaxis. CONCLUSION: The
      otolaryngologist should share in the increased awareness of latex allergy. Our
      patients who have had multiple surgical procedures or who are exposed to latex on
      a long-term basis may be at increased risk. Latex allergy should be considered
      when unexplained cardiorespiratory compromise occurs during surgery.

PMID- 11296057
TI  - Efficacy and tolerability of budesonide aqueous nasal spray treatment in patients
      with nasal polyps.
AB  - OBJECTIVE: To assess the efficacy and tolerability of once-daily treatment with
      budesonide aqueous nasal spray in patients with nasal polyps. DESIGN: Randomized,
      double-blind, placebo-controlled, parallel-group study. SETTING: Sixteen hospital
      clinics. PATIENTS: One hundred eighty-three patients with moderate-sized nasal
      polyps causing clinically significant symptoms during a 1-week run-in period.
      INTERVENTIONS: Patients were randomized to receive 1 of the following 4
      budesonide aqueous nasal spray treatments: 128 microg once daily in the morning
      and placebo in the evening, 128 microg twice daily, 256 microg once daily in the
      morning and placebo in the evening, or placebo for 8 weeks. Nasal polyp size was
      scored and peak nasal inspiratory flow was measured at clinic visits at the
      beginning and end of the run-in period and after 4 and 8 weeks' treatment.
      Patients recorded daily peak nasal inspiratory flow, symptom scores (ie, blocked
      nose, runny nose, and sneezing) and sense of smell on diary cards. MAIN OUTCOME
      MEASURES: Mean change in nasal polyp size at the end of treatment; mean changes
      in combined and individual symptom scores. RESULTS: All doses of budesonide
      aqueous nasal spray significantly (P<.01) reduced polyp size; no significant
      differences were noted between the 4 treatment groups. The mean improvement in
      clinic peak nasal inspiratory flow at 8 weeks was 65.9 L/min with budesonide
      aqueous nasal spray, 128 microg twice daily; 71.6 L/min with budesonide aqueous
      nasal spray, 256 microg once daily; and 54.6 L/min with budesonide aqueous nasal
      spray, 128 microg once daily (all P<.001 vs placebo). Combined and individual
      symptom scores and sense of smell improved significantly in all budesonide
      treated groups; the effect on symptoms became apparent within 1 to 2 days of the
      first dose. Budesonide aqueous nasal spray was well tolerated. CONCLUSIONS: Doses
      of budesonide aqueous nasal spray, 128 microg once daily, were found to be
      effective in the treatment of nasal polyps, and doses of budesonide aqueous nasal
      spray, 256 microg once daily, did not show any significant additional efficacy.

PMID- 11296058
TI  - Radiology forum: imaging quiz case 1. Diagnosis: unsuspected laryngotracheal
      foreign body (FB).

PMID- 11296059
TI  - Radiology forum: imaging quiz case 2. Diagnosis: airway foreign body (Lite-Brite
      Peg).

PMID- 11296060
TI  - Papillary cancer of the thyroid in low-risk patients: the perspective of the
      University of Texas Health Science Center at San Antonio.

PMID- 11296061
TI  - Under most circumstances, thyroid lobectomy is appropriate for low-risk patients
      with papillary cancer of the thyroid.

PMID- 11296062
TI  - Papillary carcinoma of the thyroid: extent of thyroidectomy.

PMID- 11296063
TI  - Pneumococcal conjugate vaccine: impact on otitis media and otolaryngology.

PMID- 11296064
TI  - Susac syndrome and multiple sclerosis.

PMID- 11296066
TI  - Comparison of tympanic membranes.

PMID- 11296068
TI  - Child advocacy and robust community-centered research.

PMID- 11296069
TI  - Herd immunity and the varicella vaccine: is it a good thing?

PMID- 11296070
TI  - Piracetam therapy does not enhance cognitive functioning in children with down
      syndrome.
AB  - BACKGROUND: Piracetam is widely used as a purported means of improving cognitive
      function in children with Down syndrome. Its efficacy, however, has not been
      rigorously assessed. OBJECTIVE: To determine whether 4 months of piracetam
      therapy (80-100 mg/kg per day) enhances cognitive function in children with Down
      syndrome. DESIGN: A randomized, double-blind, placebo-controlled crossover study.
      PARTICIPANTS AND METHODS: Twenty-five children with Down syndrome (aged 6.5-13
      years) and their caregivers participated. After undergoing a baseline cognitive
      assessment, children were randomly assigned to 1 of 2 treatment groups: piracetam
      placebo or placebo-piracetam. MAIN OUTCOME MEASURE: The difference in performance
      while taking piracetam vs while taking placebo on tests assessing a wide range of
      cognitive functions, including attention, learning, and memory. RESULTS: Eighteen
      children completed the study, 4 withdrew, and 3 were excluded at baseline.
      Piracetam therapy did not significantly improve cognitive performance over
      placebo use but was associated with central nervous system stimulatory effects in
      7 children: aggressiveness (n = 4), agitation or irritability (n = 2), sexual
      arousal (n = 2), poor sleep (n = 1), and decreased appetite (n = 1). CONCLUSION:
      Piracetam therapy did not enhance cognition or behavior but was associated with
      adverse effects.

PMID- 11296071
TI  - Consultations for holistic pediatric services for inpatients and outpatient
      oncology patients at a children's hospital.
AB  - BACKGROUND: As demand increases for complementary and alternative medical care,
      pediatric institutions face the need to answer patients' and clinicians'
      questions about integrating these therapies in hospital settings. OBJECTIVE: To
      describe the first year of experience in providing holistic medicine
      consultations in an urban tertiary care teaching hospital. DESIGN: Prospective
      cohort. SUBJECTS: Patients seeking consultation from the Center for Holistic
      Pediatric Education and Research, Boston, Mass, from July 16, 1999, to July 15,
      2000. METHODS: Review of consultation notes and medical records. RESULTS: Of the
      70 physician consultations, most (n = 43) were for oncology patients. Most
      consultations (n = 44) were accomplished with a single visit. The most common
      goal for consultation was to obtain help in managing symptoms such as nausea,
      pain, insomnia, or agitation (n = 50). The most common questions about specific
      therapies had to do with herbs (n = 41) or dietary supplements (n = 42), but
      there were also frequent questions about diet and nutrition (n = 33) and mind
      body therapies such as guided imagery and biofeedback (n = 28) and massage (n =
      25). Approximately 0.3 full-time equivalents of physician time was required to
      provide clinical consultations, and $7315 was collected of the $26 638 billed for
      these services. CONCLUSIONS: The complementary medicine consultation service was
      primarily consulted by oncology patients requesting assistance with pain and
      symptom management. Patients had questions about various therapies, particularly
      herbs and dietary supplements. Additional research is necessary to determine the
      cost-effectiveness of an integrated approach to care, particularly for
      institutions without access to reliable community resources for complementary and
      alternative medical therapies.

PMID- 11296072
TI  - Partial uptake of varicella vaccine and the epidemiological effect on varicella
      disease in 11 day-care centers in North Carolina.
AB  - BACKGROUND: The increasing use of varicella vaccine in children attending day
      care has rapidly decreased the incidence of wild-type varicella disease. The herd
      immunity noted is significant and will have an effect on the epidemiology of
      natural varicella. OBJECTIVE: To monitor the change in varicella incidence in day
      care attendees after the licensure of varicella vaccine. DESIGN: A prospective
      observational cohort study design. SETTING: Eleven private day-care centers and
      preschools in North Carolina participated in the study from January 1, 1995,
      through December 31, 1999. PARTICIPANTS: All children in the 11 centers were
      eligible for participation. Some participated more actively, supplying
      information on a regular basis. Others participated passively. Day-care personnel
      provided information about all cases of varicella. INTERVENTIONS: None. MAIN
      OUTCOME VARIABLES: The change in the incidence of varicella disease was
      documented as the use of varicella vaccine increased. RESULTS: Varicella vaccine
      coverage increased substantially from 4.4% in 1995 to 63.1% in December 1999. The
      vaccination rate accelerated dramatically in 1996 and 1997, leveled off in 1998,
      and rose again in 1999. Cumulative varicella incidence decreased from 16.74 cases
      per 1000 person-months in July 1996 to 1.53 cases per 1000 person-months in
      December 1999 in unvaccinated children. CONCLUSIONS: The varicella vaccination
      rate continued to increase slowly in the day-care population after an initial
      rapid uptake. The decrease in varicella disease is greater than the increase in
      varicella vaccination. This herd effect is welcome and even apparent in the
      unvaccinated children younger than 1 year.

PMID- 11296073
TI  - Identification and management of psychosocial problems by preventive child health
      care.
AB  - OBJECTIVES: To assess the degree to which physicians and nurses working in
      preventive child health care (child health professionals [CHPs]) identify and
      manage psychosocial problems in children, and to determine its association with
      parent-reported behavioral and emotional problems, sociodemographic factors, and
      general and mental health history of children. DESIGN: The CHPs examined the
      child and interviewed parents and child during their routine health assessments.
      The parents completed the Child Behavior Checklist. SETTING: Nineteen child
      health care services across the Netherlands, serving nearly all school-aged
      children routinely. SUBJECTS: Of 4970 children aged 5 through 15 years, eligible
      for a routine health assessment, 4480 (90.1%) participated. MAIN OUTCOME
      MEASURES: Identification and management of psychosocial problems by CHPs.
      RESULTS: In 25% of all children, CHPs identified 1 or more psychosocial problems.
      One in 5 identified children were referred for further diagnosis and treatment.
      Identification of psychosocial problems and subsequent referral were 6 times more
      likely in children with serious parent-reported problem behavior according to the
      Child Behavior Checklist total problem score (8% of total sample). However, CHPs
      identified no psychosocial problems in 43% of these children and therefore
      undertook no action. Other child factors associated with CHPs' identification and
      referral were past treatment for psychosocial problems, life events, and academic
      problems. After adjustment for these, sociodemographic characteristics did not
      predict referral. CONCLUSIONS: The CHPs identify psychosocial problems in school
      aged children frequently and undertake actions for most of them. Screening for
      psychosocial problems may be a promising option to reduce these problems, but
      accurate identification should be enhanced.

PMID- 11296075
TI  - Early effects of the healthy steps for young children program.
AB  - OBJECTIVE: The Healthy Steps for Young Children Program (HS) incorporates early
      child development specialists and enhanced developmental services into routine
      pediatric care. An evaluation of HS is being conducted at 6 randomization and 9
      quasi-experimental sites. Services received, satisfaction with services, and
      parent practices were assessed when infants were aged 2 to 4 months. METHODS:
      Telephone interviews with mothers were conducted for 2631 intervention (response
      rate, 89%) and 2265 control (response rate, 87%) families. Analyses were
      conducted separately for randomization and quasi-experimental sites and adjusted
      for baseline differences between intervention and control groups. Hierarchical
      linear models assessed overall adjusted effects, while accounting for within-site
      correlation of outcomes. RESULTS: Intervention families were considerably more
      likely than controls to report receiving 4 or more developmental services and
      home visits and discussing 5 infant development topics. They also were more
      likely to be satisfied and less likely to be dissatisfied with care from their
      pediatric provider and were less likely to place babies in the prone sleep
      position or feed them water. The program did not affect breastfeeding
      continuation. Differences in the percentage of parents who showed picture books
      to their infants, fed them cereal, followed routines, and played with them daily
      were found only at the quasi-experimental sites and may reflect factors unrelated
      to HS. CONCLUSIONS: Intervention families received more developmental services
      during the first 2 to 4 months of their child's life and were happier with care
      received than were control families. Future surveys and medical record reviews
      will address whether these findings persist and translate into improved language
      development, better utilization of well-child care, and an effect on costs.

PMID- 11296076
TI  - Child care and common communicable illnesses: results from the National Institute
      of Child Health and Human Development Study of Early Child Care.
AB  - OBJECTIVES: To examine the relationship between experiences in child care and
      communicable illnesses (gastrointestinal tract illness, upper respiratory tract
      infection, and ear infections or otitis media) throughout the first 3 years of
      life and to investigate whether increased frequency of these illnesses is related
      to language development, school readiness, and behavior problems. DESIGN: Health,
      child care, family, and child developmental data were obtained from more than
      1200 participants in the National Institute of Child Health and Human Development
      Study of Early Child Care, a 10-site prospective study that began at the
      participants' birth. Longitudinal logistic regression analyses were performed
      using each type of communicable illness as the outcome variable, with family,
      child, and child care variables as predictors in the model, and followed by a
      series of regression analyses with developmental measures as the outcome
      variables. RESULTS: Rates of illness were higher in children in child care than
      for children reared exclusively at home during the first 2 years of life, but the
      differences were nonsignificant by age 3 years. Number of hours in child care per
      week during the first year and number of other children in the child care
      arrangement were related to the rates of illness. There was no evidence that
      increased rates of illness have a negative effect on school readiness or language
      competence. However, there was some evidence that increased illness was
      associated with behavior problems as reported by mothers, but not by child care
      providers. CONCLUSIONS: Children in child care experience more bouts of illness
      in the first 2 years of life, but differences are negligible by age 3 years. The
      increased rates of illness bear little relation to other aspects of children's
      development, except, perhaps, for a small increase in behavior problems.

PMID- 11296077
TI  - Smoking cessation in adolescents: the role of nicotine dependence, stress, and
      coping methods.
AB  - OBJECTIVES: To compare perceived reasons for continued smoking and withdrawal
      symptoms between current smokers and quitters in an inner-city adolescent
      population. To examine the relationship of nicotine dependence, stress, and
      coping methods between smokers and quitters and, using the Transtheoretical Model
      of Change, among adjacent smoking cessation stages. DESIGN: A cross-sectional
      study using a self-administered questionnaire. PARTICIPANTS: The study comprised
      354 clinic patients between the ages of 12 and 21 years who reported past or
      present smoking. MAIN OUTCOME MEASURES: Demographic characteristics, smoking
      status, perceived reasons for continued smoking, attempts to quit, and withdrawal
      symptoms, as well as standardized scales assessing nicotine dependence, stress,
      and coping methods. RESULTS: The overall prevalence of smoking in this population
      was 26%. Smokers were significantly more likely to report smoking more cigarettes
      per day as well as higher levels of physical addiction (P<.01), greater levels of
      perceived stress (P<.02), and less use of cognitive coping methods (P<.02) than
      quitters (P<.005). However, comparison of consecutive stages revealed a
      significant difference only between precontemplation and contemplation in
      cognitive coping methods (P<.01). Three of 20 withdrawal symptoms (cravings,
      difficulty dealing with stress, and anger) were reported more frequently among
      current smokers who had attempted to quit in the last 6 months than among former
      smokers (P<.01). CONCLUSION: Interventions for inner-city adolescents who smoke
      should be designed to target those with the highest levels of nicotine
      dependence, stress, and decreased use of cognitive coping methods because they
      are the least likely to quit on their own, rather than developing stage-specific
      models.

PMID- 11296078
TI  - Intravenous ketorolac in the emergency department management of sickle cell pain
      and predictors of its effectiveness.
AB  - OBJECTIVES: To evaluate the effectiveness of intravenous (IV) ketorolac
      tromethamine in the treatment of children with sickle cell disease with moderate
      to severe acute vaso-occlusive pain (VOP) and to develop a predictive model that
      would determine who would need additional IV analgesics. DESIGN: A prospective
      case series. SETTING: The emergency department of an urban children's hospital in
      the southeastern United States. PATIENTS: A convenience sample of 51 children
      aged 6 to 18 years, representing 70 distinct episodes of VOP requiring IV
      analgesics. INTERVENTION: All patients were given 0.5 to 1 mg/kg IV ketorolac and
      IV fluids. MAIN OUTCOME MEASURES: Patients, parents, nurses, and physicians
      assessed pain before and after ketorolac using a standard 100-mm visual analog
      scale (VAS). RESULTS: Of the 70 episodes of VOP, 37 (53%) adequately resolved
      with IV ketorolac and IV fluids and required no IV opioids (group A). Thirty-one
      episodes (47%) required the addition of an IV opioid (group B). Group B had a
      significantly greater proportion of episodes reporting 4 or more painful sites
      than group A, 43% (12/28) vs 9% (3/33), respectively (P<.01). Group B also had
      significantly higher mean initial VAS scores than group A as assessed by the
      patient (81 vs 60; P<.01), parent (71 vs 54; P<.01), nurse (78 vs 51, P<.01), and
      physician (69 vs 53; P =.01). Of the patient assessments with an initial VAS
      score greater than 70, 69% (18/26) required the addition of an opioid.
      CONCLUSIONS: First-line therapy with IV ketorolac and IV fluids resulted in
      adequate resolution of pain in 53% of episodes with acute VOP. A reported 4 or
      more painful sites and an initial VAS score greater than 70 were predictors of
      the likelihood to need additional IV analgesics.

PMID- 11296079
TI  - Use of inhaled anti-inflammatory medication in children with asthma in managed
      care settings.
AB  - BACKGROUND: Many factors affect use of inhaled therapy in asthma. Relatively
      little is known about current patterns of use of anti-inflammatory medication in
      children with asthma and whether variations occur with age and use of
      bronchodilator medication. OBJECTIVE: To study the factors associated with
      dispensing of anti-inflammatory (controller) asthma medication to children in 3
      managed care organizations (MCOs). METHODS: Using automated databases, a 1-year
      cross-sectional study of children with asthma aged 3 to 15 years cared for in 3
      MCOs was used to evaluate the association of age and other factors with
      controller medication use. RESULTS: A total of 13 352 children were studied.
      Significantly fewer children aged 3 to 5 years were dispensed any (> or =1)
      controller medication than older children (P<.001). Among children dispensed 6 or
      more beta-agonists, only 39% also received 5 or more controller dispensings, with
      adolescents significantly less likely than younger children to receive 5 or more
      controllers (33%; P<.001). Significant differences were seen among MCOs in
      proportions of patients dispensed controller medication. In a multiple logistic
      regression model, controlling for frequency of beta-agonist dispensing and MCO,
      significantly lower dispensing of any controller medication was seen for those
      aged 3 to 5 years (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-0.9)
      and for girls (OR, 0.9; 95% CI, 0.8-0.96). In contrast, for repeated (> or =5)
      controller dispensing there were significantly fewer dispensings to adolescents
      (OR, 0.7; 95% CI, 0.6-0.9) and girls (OR, 0.8; 95% CI, 0.7-0.9). CONCLUSIONS:
      There may be differences in the use of preventive asthma medication in children
      that are affected by age, sex, and health care organization. Few children with
      frequent symptoms are using controllers regularly, as is recommended by national
      guidelines.

PMID- 11296080
TI  - Children in food-insufficient, low-income families: prevalence, health, and
      nutrition status.
AB  - OBJECTIVE: To examine characteristics of US children living in food-insufficient
      households and to compare food and nutrient intakes, physical inactivity, and
      overweight and underweight status of children in food-insufficient households
      with those in food-sufficient households. DESIGN: Cross-sectional, nationally
      representative sample of children and households from the Continuing Survey of
      Food Intakes by Individuals, from 1994 to 1996. PARTICIPANTS: A group of 3790
      households, including 5669 children (ages 0-17 years). MAIN OUTCOME MEASURE(S):
      Estimates of food insufficiency for children were based on the reported adequacy
      of their households, described as "often don't have enough to eat" or "sometimes
      don't have enough to eat." Nutrient consumption was based on two 24-hour dietary
      recalls from in-person interviews. RESULTS: Three percent of all households with
      children, and 7.5% of low-income families with children experienced food
      insufficiency. Several demographic and characteristic differences were observed
      between the food-sufficient and food-insufficient low-income groups. Children of
      low-income families, either food-sufficient or food-insufficient, had similar
      macronutrient and micronutrient intake, reported exercise, television watching,
      and percentage of overweight and underweight. When compared with the higher
      income food-sufficient households, children in the low-income food-insufficient
      households consumed fewer calories (P =.05) and total carbohydrates (P =.004),
      but had a higher cholesterol intake (P =.02). The low-income food-insufficient
      group included more overweight children (P =.04), consumed less fruits (P =.04),
      and spent more time watching television (P =.02). CONCLUSIONS: While not
      different from low-income families who do not report food insufficiency, low
      income families with food insufficiency had children who differed from high
      income families in several nutrition and anthropometric measures. Clinicians
      should be aware of the possible effects of poverty and lack of access to food on
      child health and nutrition status. The long-term effects of these are not yet
      known.

PMID- 11296081
TI  - Picture of the month. Hair-thread tourniquet syndrome.

PMID- 11296082
TI  - Pathological case of the month. Cystic desmoplastic medulloblastoma of infancy.

PMID- 11296083
TI  - Pathological case of the month. Retinoblastoma presenting as pseudoiritis and
      secondary glaucoma.

PMID- 11296084
TI  - Radiological case of the month. Spontaneous neonatal gastric perforation.

PMID- 11296086
TI  - The pediatric forum: bicycle burden and balance.

PMID- 11296085
TI  - Radiological case of the month. Perforation of the inferior cava as a cause of
      neonatal free intra-abdominal air.

PMID- 11296088
TI  - The pediatric forum: Weight and happiness.

PMID- 11296091
TI  - Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor
      antagonist SR141716.
AB  - BACKGROUND: SR141716, a recently developed CB1 cannabinoid receptor antagonist,
      blocks acute effects of Delta-9-tetrahydrocannabinol (THC) and other CB1
      cannabinoid agonists in vitro and in animals. These findings suggest that CB1
      receptors mediate many of the effects of marijuana, but this has not been
      evaluated in humans. METHODS: Sixty-three healthy men with a history of marijuana
      use were randomly assigned to receive oral SR141716 or a placebo in an escalating
      dose (1, 3, 10, 30, and 90 mg) design. Each subject smoked an active (2.64% THC)
      or placebo marijuana cigarette 2 hours later. Psychological effects associated
      with marijuana intoxication and heart rate were measured before and after
      antagonist and marijuana administration. RESULTS: Single oral doses of SR141716
      produced a significant dose-dependent blockade of marijuana-induced subjective
      intoxication and tachycardia. The 90-mg dose produced 38% to 43% reductions in
      visual analog scale ratings of "How high do you feel now?" "How stoned on
      marijuana are you now?" and "How strong is the drug effect you feel now?" and
      produced a 59% reduction in heart rate. SR141716 alone produced no significant
      physiological or psychological effects and did not affect peak THC plasma
      concentration or the area under the time x concentration curve. SR141716 was well
      tolerated by all subjects. CONCLUSIONS: SR141716 blocked acute psychological and
      physiological effects of smoked marijuana without altering THC pharmacokinetics.
      These findings confirm, for the first time in humans, the central role of CB1
      receptors in mediating the effects of marijuana.

PMID- 11296092
TI  - Cannabinoid antagonists: a treatment in search of an illness.

PMID- 11296093
TI  - Neural activity related to drug craving in cocaine addiction.
AB  - BACKGROUND: Crack cocaine dependence and addiction is typically associated with
      frequent and intense drug wanting or craving triggered by internal or
      environmental cues associated with past drug use. METHODS: Water O 15 positron
      emission tomography (PET) studies were used to localize alterations in synaptic
      activity related to cue-induced drug craving in 8 crack cocaine-dependent African
      American men. In a novel approach, script-guided imagery of autobiographical
      memories were used as individualized cues to internally generate a cocaine
      craving state and 2 control (ie, anger and neutral episodic memory recall) states
      during PET image acquisition. RESULTS: The mental imagery of personalized drug
      use and anger-related scripts was associated with self-ratings of robust drug
      craving or anger, and comparable alterations in heart rate. Compared with the
      neutral imagery control condition, imagery-induced drug craving was associated
      with bilateral (right hemisphere amygdala activation greater than left)
      activation of the amygdala, the left insula and anterior cingulate gyrus, and the
      right subcallosal gyrus and nucleus accumbens area. Compared with the anger
      control condition, internally generated drug craving was associated with
      bilateral activation of the insula and subcallosal cortex, left hippocampus, and
      anterior cingulate cortex and brainstem. A brain-wide pixel-by-pixel search
      indicated significant positive and negative correlations between imagery-induced
      cocaine craving and regional cerebral blood flow (rCBF) in distributed sites.
      CONCLUSIONS: The collected findings suggest the craving-related activation of a
      network of limbic, paralimbic, and striatal brain regions, including structures
      involved in stimulus-reward association (amygdala), incentive motivation
      (subcallosal gyrus/nucleus accumbens), and anticipation (anterior cingulate
      cortex).

PMID- 11296094
TI  - The scientific exegesis of desire: neuroimaging crack craving.

PMID- 11296095
TI  - Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on
      exposure to alcohol-specific cues.
AB  - BACKGROUND: Functional imaging studies have recently demonstrated that specific
      brain regions become active in cocaine addicts when they are exposed to cocaine
      stimuli. To test whether there are regional brain activity differences during
      alcohol cue exposure between alcoholic subjects and social drinkers, we designed
      a functional magnetic resonance imaging (fMRI) protocol involving alcohol
      specific cues. METHODS: Ten non-treatment-seeking adult alcoholic subjects (2
      women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking
      controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were
      recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging
      scanner, subjects were serially rated for alcohol craving before and after a sip
      of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic
      beverages, control nonalcoholic beverages, and 2 different visual control tasks.
      During picture presentation, changes in regional brain activity were measured
      with the blood oxygen level-dependent technique. RESULTS: Alcoholic subjects,
      compared with the social drinking subjects, reported higher overall craving
      ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared
      with viewing other beverage cues, only the alcoholic subjects had increased
      activity in the left dorsolateral prefrontal cortex and the anterior thalamus.
      The social drinkers exhibited specific activation only while viewing the control
      beverage pictures. CONCLUSIONS: When exposed to alcohol cues, alcoholic subjects
      have increased brain activity in the prefrontal cortex and anterior thalamus
      brain regions associated with emotion regulation, attention, and appetitive
      behavior.

PMID- 11296096
TI  - Differential circadian rhythm disturbances in men with Alzheimer disease and
      frontotemporal degeneration.
AB  - BACKGROUND: Caregiver exhaustion is a frequent consequence of sleep disturbance
      and rest-activity rhythm disruption that occurs in dementia. This exhaustion is
      the causal factor most frequently cited by caregivers in making the decision to
      institutionalize patients with dementia. Recent studies have implicated
      dysfunction of the circadian pacemaker in the etiology of these disturbances in
      dementia. METHODS: We studied the activity and core-body temperature rhythms in a
      cohort of 38 male patients with a clinical diagnosis of probable Alzheimer
      disease (AD) approximately 2 years before death. These patients were later given
      a confirmed diagnosis of AD (n = 23), frontotemporal degeneration (FTD) (n = 9),
      or diffuse Lewy body disease (DLB) with mixed AD or FTD pathologies (n = 6) after
      autopsy and neuropathological examination. Physiological rhythms of patients with
      AD and FTD were then compared with a group of normal, elderly men (n = 8) from
      the community. RESULTS: Alzheimer patients showed increased nocturnal activity
      and a significant phase-delay in their rhythms of core-body temperature and
      activity compared with patients with FTD and controls. The activity rhythm of FTD
      patients was highly fragmented and phase-advanced in comparison with controls and
      apparently uncoupled from the rhythm of core-body temperature. CONCLUSIONS:
      Patients with AD and patients with FTD show different disturbances in their
      rhythms of activity and temperature compared with each other and with normal
      elderly patients.

PMID- 11296097
TI  - Advancing paternal age and the risk of schizophrenia.
AB  - BACKGROUND: A major source of new mutations in humans is the male germ line, with
      mutation rates monotonically increasing as father's age at conception advances,
      possibly because of accumulating replication errors in spermatogonial cell lines.
      METHOD: We investigated whether the risk of schizophrenia was associated with
      advancing paternal age in a population-based birth cohort of 87 907 individuals
      born in Jerusalem from 1964 to 1976 by linking their records to the Israel
      Psychiatric Registry. RESULTS: Of 1337 offspring admitted to psychiatric units
      before 1998, 658 were diagnosed as having schizophrenia and related nonaffective
      psychoses. After controlling for maternal age and other confounding factors (sex,
      ethnicity, education [to reflect socioeconomic status], and duration of marriage)
      in proportional hazards regression, we found that paternal age was a strong and
      significant predictor of the schizophrenia diagnoses, but not of other
      psychiatric disorders. Compared with offspring of fathers younger than 25 years,
      the relative risk of schizophrenia increased monotonically in each 5-year age
      group, reaching 2.02 (95% confidence interval, 1.17-3.51) and 2.96 (95%
      confidence interval, 1.60-5.47) in offspring of men aged 45 to 49 and 50 years or
      more, respectively. Categories of mother's age showed no significant effects,
      after adjusting for paternal age. CONCLUSIONS: These findings support the
      hypothesis that schizophrenia may be associated, in part, with de novo mutations
      arising in paternal germ cells. If confirmed, they would entail a need for novel
      approaches to the identification of genes involved in schizophrenia.

PMID- 11296098
TI  - Anxiolyticlike effects of atrial natriuretic peptide on cholecystokinin
      tetrapeptide-induced panic attacks: preliminary findings.
AB  - BACKGROUND: Panic attacks induced by administration of cholecystokinin
      tetrapeptide (CCK-4) have been evaluated as a valuable tool to investigate the
      neurobiological mechanisms involved in panic anxiety. The rationale to study the
      effects of natriuretic peptides on the CCK-4 response is derived from
      observations that atrial natriuretic peptide (ANP) is released during panic
      attacks in humans and has anxiolyticlike actions in various animal models.
      METHODS: A double-blind, placebo-controlled design was conducted in 9 patients
      with panic disorder and 9 similar healthy control subjects. After pretreatment
      with an infusion of 150 microg of ANP or placebo in random order, each subject
      received 50 microg of CCK-4. Psychopathological parameters as well as
      physiological measures were sampled before and after CCK-4 administration.
      RESULTS: After pretreatment with ANP, the number of CCK-4-induced panic attacks
      decreased from 8 to 6 in patients and from 5 to 2 in controls. Acute Panic
      Inventory ratings were significantly reduced in patients after ANP vs placebo
      pretreatment. Infusion of ANP significantly curtailed the CCK-4-induced release
      of corticotropin in patients. Heart rate variability analysis indicated a
      sympathetic stimulation by CCK-4 that was inhibited by ANP in patients and
      controls. CONCLUSIONS: The present study indicates that ANP exerts anxiolyticlike
      effects on CCK-4-stimulated anxiety attacks in patients with panic disorder. In
      addition, ANP produced an inhibition of the hypothalamopituitary-adrenocortical
      system and sympatholytic effects.

PMID- 11296100
TI  - Parental and early childhood predictors of persistent physical aggression in boys
      from kindergarten to high school.
AB  - BACKGROUND: In a prior study, we identified 4 groups following distinct
      developmental courses, or trajectories, of physical aggression in 1037 boys from
      6 to 15 years of age in a high-risk population sample from Montreal, Quebec. Two
      were trajectories of high aggression, a persistently high group and a high but
      declining group. The other 2 trajectories were a low group and a moderate
      declining group. This study identified early predictors of physical aggression
      trajectories from ages 6 to 15 years. METHODS: In this study, logistic regression
      analysis was used to identify parental and child characteristics that
      distinguished trajectory group membership. RESULTS: For boys displaying high
      hyperactivity and high opposition in kindergarten, the odds of membership in the
      2 high aggression groups were increased by factors of 3.0 (95% confidence
      interval [CI], 2.0-4.3) and 2.7 (95% CI, 1.9-3.8), respectively, compared with
      boys without these risks. Counterpart odds ratios for the risk factors of
      mothers' teen-onset of parenthood and low educational attainment were 1.6 (95%
      CI, 1.1-2.2) and 1.8 (95% CI, 1.3-2.4), respectively. Only the maternal
      characteristics distinguished between the trajectory of persistently physical
      high aggression and the trajectory starting high but subsequently declining. For
      the 2 maternal risk factors combined, the odds ratio of persisting in high level
      physical aggression was 9.4 (95% CI, 2.9-30.4). CONCLUSIONS: Kindergarten boys
      displaying high levels of opposition and hyperactivity are at high risk of
      persistent physical aggression. However, among kindergarten boys who display high
      levels of physical aggression, only mothers' low educational level and teenage
      onset of childbearing distinguish those who persist in high levels of physical
      aggression.

PMID- 11296099
TI  - Preventing recurrent depression using cognitive therapy with and without a
      continuation phase: a randomized clinical trial.
AB  - BACKGROUND: Cognitive therapy (CT) may reduce depressive relapse and recurrence
      when patients learn and use the associated skills. Reported relapse and
      recurrence rates after CT discontinuation vary widely. The factors that determine
      when CT is preventive remain unidentified. We developed continuation-phase CT (C
      CT) to teach responders skills to prevent relapse. This is the first randomized
      trial comparing CT with and without a continuation phase in responders to CT who
      were vulnerable, given their history of recurrent unipolar depression. METHODS:
      Patients aged 18 to 65 years (n = 156) with recurrent DSM-IV major depressive
      disorder (MDD) entered 20 sessions of acute-phase CT (A-CT). Unmedicated
      responders (ie, no MDD and 17-item Hamilton Rating Scale for Depression score <
      or =9; n = 84) were randomized to either 8 months (10 sessions) of C-CT or
      control (evaluation without CT). Follow-up lasted an additional 16 months. A
      clinician blind to assignment evaluated relapse and recurrence (ie, DSM-IV MDD).
      RESULTS: Over an 8-month period, C-CT significantly reduced relapse estimates
      more than control (10% vs 31%). Over 24 months, including the CT-free follow-up,
      age of onset and quality of remission during the late phase of A-CT each
      interacted with condition assignment to influence durability of effects. In
      patients with early-onset MDD, C-CT significantly reduced relapse and recurrence
      estimates (16% vs 67% in control). When patients had unstable remission during
      late A-CT, C-CT significantly reduced relapse and recurrence estimates to 37% (vs
      62% in control). CONCLUSIONS: Findings suggest that 8 months of C-CT
      significantly reduces relapse and recurrence in the highest-risk patients with
      recurrent MDD. Risk factors influenced the necessity for C-CT.

PMID- 11296101
TI  - Treatment process and outcomes for managed care patients receiving new
      antidepressant prescriptions from psychiatrists and primary care physicians.
AB  - BACKGROUND: While many studies describe deficiencies in primary care
      antidepressant treatment, little research has applied similar standards to
      psychiatric practice. This study compares baseline characteristics, process of
      care, and outcomes for managed care patients who received new antidepressant
      prescriptions from psychiatrists and primary care physicians. METHODS: At a
      prepaid health plan in Washington State, patients receiving initial
      antidepressant prescriptions from psychiatrists (n = 165) and primary care
      physicians (n = 204) completed a baseline assessment, including the Structured
      Clinical Interview for DSM-IV depression module, a 20-item depression assessment
      from the Symptom Checklist-90, and the Medical Outcomes Survey 36-Item Short-Form
      Health Survey functional status questionnaire. All measures were repeated after 2
      and 6 months. Computerized data were used to assess antidepressant refills and
      follow-up visits over 6 months. RESULTS: At baseline, psychiatrists' patients
      reported slightly higher levels of functional impairment and greater prior use of
      specialty mental health care. During follow-up, psychiatrists' patients made more
      frequent follow-up visits, and the proportion making 3 or more visits in 90 days
      was 57% vs 26% for primary care physicians' patients. The proportion receiving
      antidepressant medication at an adequate dose for 90 days or more was similar
      (49% vs 48%). The 2 groups showed similar rates of improvement in all measures of
      symptom severity and functioning. CONCLUSIONS: In this sample, clinical
      differences between patients treated by psychiatrists and primary care physicians
      were modest. Shortcomings in depression treatment frequently noted in primary
      care (inadequate follow-up care and high rates of inadequate antidepressant
      treatment) were also common in specialty practice. Possible selection bias limits
      any conclusions about relative effectiveness or cost-effectiveness.

PMID- 11296102
TI  - Is prefrontal cortex thinning specific for antisocial personality disorder?

PMID- 11296104
TI  - Testosterone's effects not limited to mood.

PMID- 11296106
TI  - Tenax propositi on uncharted seas.

PMID- 11296107
TI  - The effect of surgery and grade on outcome of gastrointestinal stromal tumors.
AB  - HYPOTHESIS: Gastrointestinal stromal tumors (GIST) are aggressive, rare, and
      difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior
      of these tumors can be predicted by reproducible prognostic factors. DESIGN AND
      SETTING: A retrospective review of all patients (N = 70) with GIST treated at a
      tertiary care center from 1973 to 1998. PATIENTS: Adequate data for evaluation
      were available for 69 patients. Male-female distribution was 40:29. Median age
      was 60 years. Median follow-up duration was 38 months. MAIN OUTCOME MEASURES:
      Tumor grade, stage, and histologic subtype at presentation; effect of grade,
      surgery and adjuvant therapy on recurrence, salvage, and survival. RESULTS: Tumor
      distribution included 61% in the upper, 23% in the middle, and 16% in the lower
      digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors
      with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in
      the series. Distant disease at initial visit occurred in 49% of patients.
      Complete gross resection occurred in 59% of patients. After complete resection,
      the 5-year survival rate was 42%, compared with 9% after incomplete resection
      (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated
      any significant benefit. Among 39 patients who were disease free after complete
      resection, 2% developed lymph node recurrence, 25% developed local recurrence,
      and 33% developed distant recurrences (54% liver, 20% peritoneum). By
      multivariate analysis the risk of local and/or distant metastases was
      significantly increased for tumors with more than 1 mitosis and size larger than
      5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete
      resection, age greater than 50 years, non-smooth muscle histological feature,
      tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly
      decreased survival. CONCLUSION: Complete gross surgical resection is presently
      the only means of cure for GIST. Tumors with more than 1 mitosis and a size
      larger than 5 cm have an especially poor prognosis, with decreased survival, and
      increased local and/or distant recurrence.

PMID- 11296108
TI  - Ten-year experience with 733 pancreatic resections: changing indications, older
      patients, and decreasing length of hospitalization.
AB  - HYPOTHESIS: Experience with pancreatic resection for the last 10 years has
      resulted in new trends in patient characteristics and, for
      pancreaticoduodenectomy (PD), a decrease in the length of stay (LOS). This
      decrease is due in part to the implementation of case management and clinical
      pathways. DESIGN: Retrospective case series of patients undergoing pancreatic
      resection. SETTING: A university-affiliated, tertiary care referral center.
      PATIENTS: The study comprised 733 consecutive patients undergoing pancreatic
      resection for benign or malignant disease at the Massachusetts General Hospital
      in Boston from April 1990 to March 2000. INTERVENTIONS: Of the 733 pancreatic
      resections, 489 were PD; 190, distal pancreatectomy; 40, total pancreatectomy;
      and 14, middle-segment pancreatectomy. MAIN OUTCOME MEASURES: Length of stay;
      occurrence of delayed gastric emptying, pancreatic fistula, reoperation,
      readmission, or other complications; mortality; and comparison of patients in 3
      periods according to the implementation of case management (July 1995) and
      clinical pathways (September 1998). RESULTS: For PD, patients in group 1 (April
      1990 to June 1995) were significantly younger (mean +/- SD, 57 +/- 15 years) than
      those in group 2 (July 1995 to August 1998; mean +/- SD, 62 +/- 13 years) and
      group 3 (September 1998 to October 2000; mean +/- SD, 65 +/- 13 years)(P <.01).
      Over time, the proportion of PD for cystic tumors increased from 9.9% to 20% (P
      =.01), and the proportion of PD for chronic pancreatitis decreased from 23% to
      10% (P <.01). Use of pylorus-preserving PD decreased from 45% to 0% (P <.001).
      Delayed gastric emptying decreased from 17% to 6.1% (P <.01). Pancreatic fistula,
      reoperation, and mortality were unchanged. Length of stay for PD decreased from
      16.1 +/- 0.6 to 9.5 +/- 0.4 days (mean +/- SE) (P <.001). Multivariate analysis
      showed that period, case volume, pylorus-preserving PD, and presence of
      complications are all independent predictors of LOS (P <.05 for all). For distal
      pancreatectomy, patients in groups 2 and 3 were older than those in group 1 (mean
      +/- SD, 57 +/-14 vs 52 +/- 17 years) (P <.05). Resections for cystic tumors
      increased from 26% to 52% (P <.05), and resections for chronic pancreatitis
      decreased from 32% to 14% (P =.06). Median LOS decreased from 9 days to 6. For
      total pancreatectomy, resections for cystic tumors increased from 18% to 43%.
      Median LOS decreased from 14.5 days to 11. For all resections, case volume
      increased from 4 resections per month in 1990 to 5.8 in 1995 and 12 in 2000 (r =
      0.83; P <.001). CONCLUSIONS: Older patients are increasingly being selected for
      pancreatic resection. This reflects an increasing frequency of operations
      performed for cystic tumors and fewer for chronic pancreatitis. With the
      exception of delayed gastric emptying, complications and mortality have remained
      the same or decreased slightly during the past 10 years. However, there has been
      a significant decrease in LOS; this is the result of implementation of case
      management and clinical pathways, increasing case volume, decreasing incidence of
      delayed gastric emptying, and decreasing use of pylorus-preserving PD.

PMID- 11296109
TI  - Management and outcome of complications after laparoscopic antireflux operations.
AB  - HYPOTHESIS: Perioperative complications of laparoscopic antireflux operations are
      infrequent and treatable and do not cause permanent disability. DESIGN:
      Retrospective review of all patients with laparoscopic antireflux operations for
      the management and outcome of all complications. SETTING: University medical
      center. PATIENTS: All 538 patients who underwent operation from January 20, 1993,
      through December 28, 1999. MAIN OUTCOME MEASURES: Complications were defined as
      any major or minor deviation from the standard postoperative clinical pathway.
      Minor complications did not require invasive treatment and were not expected to
      result in permanent disability. Major complications required invasive treatment
      or could result in permanent disability. The frequency of complications was also
      stratified into those that occurred during primary antireflux procedures and
      those that occurred during reoperations for previously failed procedures.
      RESULTS: Ninety-two complications occurred in 538 operations (17.1%). Sixty-eight
      patients (12.6%) experienced minor complications. Postoperative ileus was the
      most common complication (n = 37 [6.9%]), followed by pneumothorax (n = 13
      [2.4%]) and urinary retention (n = 10 [1.9%]). Major complications were present
      in only 24 patients (4.5%) and occurred significantly more frequently after
      reoperations. Of these, dysphagia was the most frequent complication observed (n
      = 11 [2.0%]), followed by perforated viscus (n = 4 [0.7%]). Two patients (0.4%)
      died. All but 4 major complications resulted in full recovery. CONCLUSIONS: Major
      complications in laparoscopic antireflux surgery are rare, their treatment is
      straightforward, and permanent disability is uncommon. Complications occur twice
      as often during reoperations, highlighting the difficulty in performing these
      procedures. Although primary laparoscopic antireflux operations are performed by
      many general surgeons routinely, reoperations should be performed by a team
      experienced in laparoscopic esophageal surgery.

PMID- 11296110
TI  - Is unplanned return to the operating room a useful quality indicator in general
      surgery?
AB  - HYPOTHESIS: To test our hypothesis that unplanned return to the operating room
      (OR) is a useful quality indicator, we examined how often and for what reasons
      patients go back to the OR in a broad-based general surgery practice. DESIGN AND
      SETTING: Prospective cohort study at a rural tertiary care center. PATIENTS:
      Consecutive series of 3044 patients undergoing general surgery procedures in the
      OR between September 1, 1998, and March 31, 2000. Information about all
      postoperative adverse events occurring before discharge or within 30 days
      (whichever was longer) was collected prospectively. Unplanned return to the OR
      was defined as any secondary procedure required for a complication resulting
      directly or indirectly from the index operation. MAIN OUTCOME MEASURES: Unplanned
      return to the OR, mortality, and hospital charges. RESULTS: Overall, 107 (3.5%)
      had an unplanned return to the OR. A relatively small number of inpatient
      procedures accounted for a disproportionate share of unplanned reoperations,
      including colon resection (18% of total reoperations), renal transplant (9%),
      gastric bypass (6%), and pancreatic resection (6%). As expected, hospital charges
      were markedly higher for patients with unplanned returns to the OR. Reoperation
      was also associated with higher mortality rates; statistically significant
      increases were noted for pancreatic resection (33% vs 3.7%; P =.04),
      esophagogastrectomy (100% vs 4.2%; P =.002), and laparoscopic Nissen
      fundoplication (50% vs 0%; P =.01). Overall, 91 reoperations (85%) were for
      complications occurring at the original surgical site, including those related to
      an anastomosis (n = 16), surgical wound (n = 21), infection (n = 16), bleeding (n
      = 12), and other (n = 26). CONCLUSIONS: Unplanned returns to the OR occur across
      a broad spectrum of general surgical procedures and carry significant
      implications. Because they most often reflect problems related to the procedure
      itself, reoperation rates may be useful for monitoring quality across hospitals
      and for identifying opportunities for quality improvement locally.

PMID- 11296112
TI  - Beyond requirements: residency management through the Internet.
AB  - HYPOTHESIS: An Internet application could collect information to satisfy
      documentation required by the Residency Review Committee. Beyond replacing a
      difficult and inefficient paper system, it would collect, process, and distribute
      information to administration, faculty, and residents. DESIGN: Descriptive study.
      SETTING: An integrated residency of 18 services at a university teaching hospital
      with 4 affiliated institutions. PARTICIPANTS: Residency administrators, faculty,
      and residents. INTERVENTIONS: The application included a procedure recorder,
      resident evaluation of faculty and rotations, goals and objectives (stratified by
      service and resident level), and matching faculty evaluation of residents with
      these goals as competencies. Policies, schedules, research opportunities,
      clinical site information, and curriculum support were created. MAIN OUTCOME
      MEASURES: Degree of compliance with Residency Review Committee standards, number
      of deficiencies corrected, and quantity and quality of information available to
      administration, faculty, and residents. RESULTS: The Internet system increased
      resident compliance for faculty and rotation evaluations from 20% and 34%,
      respectively, to 100%, which was maintained for 22 months. These evaluations can
      be displayed individually, in summary grids, and as postgraduate year-specific
      averages. Faculty evaluations of residents can be reviewed throughout the system.
      The defined category report for procedures, which had deficiencies in the
      preceding 6 years, had none for the last 2 years. The Internet application
      provides Accreditation Council for Graduate Medical Education-validated operative
      logs to regulatory agencies. CONCLUSIONS: A Web-based system can satisfy
      requirements and provide processed data that are of better quality and more
      complete than our paper system. We are now able to use scarce time and personnel
      to nurture developing surgical residents instead of shuffling paper.

PMID- 11296113
TI  - Repair of pectus excavatum deformities in children: a new perspective of
      treatment using minimal access surgical technique.
AB  - HYPOTHESIS: Minimally invasive correction of pectus excavatum (PE) deformities of
      the anterior chest wall in children is safe and effective. DESIGN: Prospective
      cohort study. SETTING: Tertiary pediatric referral center. PATIENTS: Between
      February 1996 and July 2000, 36 patients underwent minimally invasive repair
      (MIR) of PE deformities, and 6 patients had traditional Ravitch repairs (RR).
      MAIN OUTCOME MEASURES: Morbidity, operating time, estimated blood loss, days to
      tolerating a regular diet, and length of hospital stay. RESULTS: Thirty-six
      children underwent MIR for moderate to severe chest wall deformities, with a mean
      operative time of 1.6 hours, a mean blood loss of 22 mL, a mean time to
      tolerating a regular diet of 2.9 days, no intensive care unit admissions, and a
      mean length of hospital stay of 5.5 days. Six children had RR procedures
      performed for moderate to severe deformity, with a mean operative time of 5.2
      hours, a mean blood loss of 222 mL, a mean time to tolerating a regular diet of
      3.3 days, 2 patients admitted to the intensive care unit, and a mean length of
      hospital stay of 4.5 days. Complications for both procedures consisted mainly of
      postoperative pneumothorax. CONCLUSIONS: The MIR technique for PE is less
      invasive, less morbid, and better tolerated than traditional open RR of this
      common pediatric chest wall deformity. Elective surgical reconstruction can be
      safely performed in children rather than limiting repair to only symptomatic
      patients with severe deformities.

PMID- 11296114
TI  - Live donor adult liver transplantation using right lobe grafts: donor evaluation
      and surgical outcome.
AB  - HYPOTHESIS: Live donor adult liver transplantation (LDALT) is a safe and
      efficacious treatment for patients with end-stage liver disease. DESIGN: Case
      control study. SETTING: Hepatobiliary surgery and liver transplantation unit.
      PATIENTS: From December 10, 1998, through April 10, 2000, a single team performed
      15 LDALT procedures with 2 simultaneous living donor kidney transplants. During
      this period, 66 potential donors were screened and evaluated. INTERVENTIONS:
      Potential donors were evaluated with 3-dimensional helical computed tomographic
      scan, including volume renderings for hepatic lobar volume, vascular anatomy,
      virtual resection planes, and morphologic features. Suitable donors undergo
      complete medical and psychiatric evaluation and preoperative arteriography. MAIN
      OUTCOME MEASURES: Donor demographics, evaluation data, operative data, hospital
      length of stay, and morbidity. RESULTS: A total of 38 men (58%) and 28 women
      (42%) were evaluated with 15 donors participating in LDALT. Two additional donors
      provided kidney grafts for simultaneous transplantation at the time of LDALT.
      Thirty-two donors (48%) were rejected for either donor or recipient reasons, and
      10 patients (15%) elected not to participate after initial screening. Three
      dimensional volume renderings by helical computed tomographic scan predicted
      right lobe liver volume within 92% of actual graft volume. Donor morbidity,
      including all complications, was 67% with no mortality. Residual liver
      regenerated to approximately 70% of initial volume within 1 week and 80% within 1
      month after surgery. CONCLUSIONS: Donor evaluation is an important component of
      LDALT. Significant donor morbidity is encountered even with careful selection. To
      minimize donor morbidity, groups considering initiating living donor programs
      should have expertise in hepatic resection and vena cava preservation using the
      "piggyback" technique during liver transplantation.

PMID- 11296115
TI  - Routine fiberoptic endoscopic evaluation of swallowing following prolonged
      intubation: implications for management.
AB  - HYPOTHESIS: Fiberoptic endoscopic evaluation of swallowing (FEES) will identify
      patients who are at high risk for pulmonary aspiration due to swallowing
      dysfunction after prolonged intubation. Based on the results of FEES, dietary
      recommendations can be made to decrease the incidence of aspiration after
      prolonged intubation. DESIGN: Patients who were intubated for at least 48 hours
      were evaluated for swallowing dysfunction by bedside FEES within 48 hours of
      extubation. Differences in potential risk factors between aspirators and
      nonaspirators were analyzed. Dietary recommendations were made and patients were
      followed up for signs of clinically significant aspiration. SETTING: Community
      teaching hospital. PATIENTS: Fifty-one consecutive patients with no previously
      documented swallowing disorder who required a minimum of 48 hours of intubation
      for mechanical ventilation. INTERVENTIONS: Fiberoptic endoscopic evaluation of
      swallowing was performed by a speech pathologist. Initial diet orders were
      determined by results of the swallowing study. MAIN OUTCOME MEASURES: Incidence
      of swallowing dysfunction following prolonged intubation and incidence of
      clinically significant aspiration following initiation of oral feeding. RESULTS:
      Incidence of swallowing dysfunction was 56% (27/48); 12 (25%) of 48 patients were
      silent aspirators. In comparing aspirators with nonaspirators, no significant
      differences in potential risk factors or comorbidities were seen. Nineteen (70%)
      of the 27 patients aspirated with thin-consistency test liquids, and the other 8
      (30%) with puree consistency. No patients in this study group developed a
      clinically significant aspiration following initiation of appropriately modified
      diets. CONCLUSIONS: Fiberoptic endoscopic evaluation of swallowing identified
      swallowing dysfunction in more than 50% of patients intubated for longer than 48
      hours, many of whom are silent aspirators. Dietary recommendations based on FEES
      results prevented clinically significant aspiration.

PMID- 11296116
TI  - Intra-abdominal abscess after laparoscopic appendectomy for perforated
      appendicitis.
AB  - HYPOTHESIS: The incidence of postoperative intra-abdominal abscess is higher
      after laparoscopic compared with open appendectomy for perforated appendicitis.
      METHODS: A historical cohort study of pediatric patients operated on for
      suspected appendicitis by open appendectomy or laparoscopic appendectomy compares
      the incidence of postoperative intra-abdominal abscess for each procedure.
      SETTING: A tertiary care center. PATIENTS: Five hundred thirty-eight pediatric
      patients were operated on for suspected appendicitis at our institution between
      1974 and 1999. Of these, 453 were included in the study. Of the excluded
      patients, 9 had incomplete medical records, 69 had normal or interval
      appendectomies, and 7 had appendixes removed by methods other than laparoscopy or
      right lower quadrant incision. INTERVENTIONS: Open appendectomy performed through
      a right lower quadrant incision or laparoscopic appendectomy performed through a
      3-trocar approach by 1 of 3 pediatric surgeons at our institution. MAIN OUTCOME
      MEASURE: The incidence of postoperative intra-abdominal abscess after
      laparoscopic vs open appendectomy. RESULTS: In perforated appendicitis (170
      patients), the incidence of postoperative abscess after laparoscopic appendectomy
      was 24% vs 4.2% after open appendectomy. The relative risk ratio of developing a
      postoperative abscess after perforated appendicitis was 5.6 (confidence interval,
      2.1-16.0) after laparoscopic vs open appendectomy. The results remained
      significant when controlled for age, sex, intraoperative irrigation, and
      preoperative antibiotics. Postoperative abscess in all acute, gangrenous, and
      perforated appendicitis after laparoscopic appendectomy was 6.4% vs 3.0% after
      open appendectomy. This was not statistically significant. CONCLUSION: There is a
      significant increase in the incidence of postoperative intra-abdominal abscess
      with perforated appendicitis after laparoscopic compared with open appendectomy
      in pediatric patients.

PMID- 11296117
TI  - The history of surgery in Massachusetts.

PMID- 11296118
TI  - History of surgery in Maine.

PMID- 11296119
TI  - A biography of Connecticut surgery.

PMID- 11296120
TI  - History of surgery in Rhode Island.

PMID- 11296121
TI  - The history of surgery in Vermont.

PMID- 11296122
TI  - Prolonged preservation time obviates the benefits of 0 HLA mismatches in renal
      transplantation.

PMID- 11296123
TI  - Weight as a potential confounding factor for 5-year kidney graft survival.

PMID- 11296124
TI  - Special feature: image of the month.

PMID- 11296126
TI  - Moments in surgical history: extramural medical schools.

PMID- 11296128
TI  - Leukemia vaccines.
AB  - Leukemia is susceptible to immune-mediated therapies such as allogeneic stem-cell
      transplantation, donor lymphocyte infusion, and interferon. The clinical
      effectiveness of these immune-based modalities has encouraged interest in vaccine
      therapies for leukemia. Substantial progress has recently been made in basic
      immunology, allowing scientifically based vaccination strategies to be developed.
      The discovery of leukemia- specific and leukemia-associated antigens will allow
      antigen-specific therapeutic strategies to be developed. Vaccination with
      genetically modified leukemia cells and the use of dendritic cells in various
      vaccination approaches are all promising avenues of study for development of
      effective leukemia vaccines.

PMID- 11296129
TI  - Therapy for fungal infections in leukemia.
AB  - Invasive fungal infections remain a common cause of morbidity and mortality among
      patients with leukemia who become further compromised by neutropenia. Candida and
      Aspergillus spp account for the vast majority of these infections, but other,
      less commonly recognized fungi can cause life-threatening infection in these
      hosts as well. The earlier, more limited antifungal armamentarium of
      ketoconazole, flucytosine, and amphotericin B has been substantially augmented by
      the availability of fluconazole, itraconazole, and the lipid-associated
      amphotericin formulations. Intense clinical study has focused on the use of these
      agents in empiric treatment, treatment of suspected or proven infection, and
      prophylaxis. Recognition of the limitations of antifungal therapy in the
      neutropenic host has led to evaluation of the adjunctive role of immunotherapy.

PMID- 11296130
TI  - The biology of acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is a disease associated with fusion
      oncoproteins invariably involving the retinoic acid receptor (Raralpha). Retinoic
      acid induces differentiation in APL cells and is successfully used in conjunction
      with chemotherapy to treat and cure a significant percentage of patients with
      APL. APL is also a model for disruption of normal retinoid-mediated transcription
      resulting in blocked differentiation. The study of the molecular mechanisms of
      APL oncogenesis has revealed novel interactions between fusion oncoproteins and
      transcriptional coregulators, already leading to new treatment strategies.

PMID- 11296131
TI  - Novel treatment strategies in chronic lymphocytic leukemia.
AB  - The recent introduction of new active agents has led to a renaissance of clinical
      investigation in chronic lymphocytic leukemia (CLL). These agents include three
      purine analogues, (pentostatin, fludarabine, and cladribine) and two monoclonal
      antibodies (rituximab and CAMPATH I-H). Careful clinical studies have allowed for
      the development of novel combinations of two and even three non-cross- resistant
      agents. These preliminary studies indicate that such combinations can induce
      complete responses in a larger proportion of patients than can single-agent
      therapy. In CLL, survival is superior for patients achieving a complete response
      compared with patients achieving a partial response. Therefore, strategies
      designed to induce high-quality responses in the majority of patients may one day
      lead to improved survival or possibly even cure in patients with chronic
      lymphocytic leukemia.

PMID- 11296132
TI  - STI571: a gene product-targeted therapy for leukemia.
AB  - Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem-cell disorder
      characterized by the (9:22) translocation and resultant production of the
      constitutively activated bcr-abl tyrosine kinase. Characterized clinically by
      marked myeloid proliferation, it invariably terminates in an acute leukemia.
      Conventional therapeutic options include interferon-based regimens and stem-cell
      transplantation, with stem-cell transplantation being the only curative therapy.
      Through rational drug development, STI571, a bcr-abl tyrosine kinase inhibitor,
      has emerged as a paradigm for gene product-targeted therapy, offering new hope
      for expanded treatment options for patients with CML.

PMID- 11296133
TI  - Models of chronic myeloid leukemia.
AB  - Models of chronic myeloid leukemia (CML) have proven invaluable for furthering
      our understanding of the molecular pathophysiology of this disease.
      Xenotransplantation of primary human CML cells into immunodeficient mice allows
      investigation into the nature of the most primitive repopulating cells in this
      leukemia, but the system is limited by variability and difficulty with
      experimental manipulation. Accordingly, a large effort has been invested in
      developing models of CML through expression of the BCR/ABL oncogene in the
      hematopoietic system of laboratory mice. Despite numerous attempts, an accurate
      transgenic mouse model of CML has not been produced, possibly because of the
      toxicity of BCR/ABL. Conditional transgenic mice are a promising new approach to
      this problem. A more successful strategy is retroviral transduction of BCR/ABL
      into mouse bone marrow in vitro, followed by transplantation into syngeneic or
      immunodeficient recipient mice. Recipients of marrow transduced with p210 BCR/ABL
      develop a fatal myeloproliferative illness that closely resembles human CML. This
      model is being used to define the signaling pathways required for leukemogenesis
      by BCR/ABL, and for developing new therapeutic approaches.

PMID- 11296135
TI  - Gene expression profiling of lymphomas.
AB  - The functional phenotype of a cell results from the simultaneous action of many
      thousands of genes, which until recently could not be assessed using standard
      molecular biological techniques. Indeed, molecular genetics and cellular biology
      inadequately explain the molecular physiology of normal and diseased cells and
      provide a fragmented view of the role of various genes and their products. Recent
      advances in techniques of large-scale gene expression allow simultaneous study of
      thousands of genes of interest in a specific tissue/tumor of interest, and the
      ability to identify expression signatures associated with functional phenotypes.
      The application of gene expression profiling to lymphomas has already led to
      identification of distinct expression signatures associated with a germinal
      center cell and activated B-cell phenotype, and to the differentiation of tumor
      cells based on these stages of development. The differentiation of two stages of
      developmental arrest in large B-cell lymphomas suggests that this subtype is
      comprised of two diseases, albeit of similar histologic and immunophenotypic
      character, which were shown to have dramatically different outcomes following
      chemotherapy. Important information will also be obtained through the association
      of genes of unknown activity with functional cellular phenotypes and expression
      signatures, possibly leading to identification of new genes involved in
      lymphomagenesis and new targets for treatment.

PMID- 11296136
TI  - New drug development in non-Hodgkin lymphomas.
AB  - The non-Hodgkin lymphomas (NHL) are characterized by initial responsiveness to a
      variety of chemotherapeutic regimens. Nevertheless, most patients progress and
      die from their disease. A number of new agents with unique mechanisms of action
      are in clinical development. Agents that are currently considered to be the most
      promising include those that induce apoptosis; those that interfere with cell
      cycling, tumor-associated angiogenesis, farnesylation of the Ras gene, and
      histone deacetylase; and those that inhibit the proteasome, among others.
      Increasing insights into the differences between tumors and among patients will
      lead to more individualized therapeutic strategies using agents directed at
      specific genetic and immunologic targets. More rapid accrual to high-quality
      clinical studies will facilitate dissemination of new agents to patients and lead
      to an increased cure rate for NHL.

PMID- 11296137
TI  - HIV-associated lymphomas.
AB  - Intermediate and high-grade non-Hodgkin lymphomas (NHL) with a B-cell phenotype
      are AIDS-defining illnesses. The incidence of systemic NHL is over 100 times
      increased, primary central nervous system NHL is over 3000 times increased, and
      Hodgkin's disease is approximately 10 times increased in the HIV-infected
      population. Unusual extranodal presentations of NHL and Hodgkin's disease are
      seen in HIV-infected individuals. High-grade histologies are common for both NHL
      and Hodgkin's disease in the HIV setting. Treatment approaches may be changing
      with the advent of highly active antiretroviral therapy, which may allow patients
      to tolerate more intensive treatment.

PMID- 11296138
TI  - Positron emission tomography and gallium metabolic imaging in lymphoma.
AB  - Metabolic imaging allows the recognition of active tumor mass because of its
      fixed tracer. For patients with Hodgkin's disease and non-Hodgkin lymphoma,
      (67)gallium and (18)fluorodeoxyglucose (FDG) have been employed. This review
      describes the role of (67)gallium scintigraphy (Ga-scan) and positron emission
      tomography (PET) in the staging and follow-up of patients with lymphoma. These
      tools do not appear to be more powerful than conventional imaging for initial
      staging and treatment choice. Ga-scan is only valid for thoracic examination. PET
      imaging following treatment resolves the problem of persisting images on CT scan;
      nearly all patients with FDG uptake have an early relapse. Whether this
      examination will allow for intensified treatment and possible cure of more
      patients is yet to be demonstrated.

PMID- 11296140
TI  - Early-stage Hodgkin's disease.
AB  - Treatment of Hodgkin's disease (HD) is strictly dependent on stage. Historically,
      early-stage HD included the limited stages I, II, and IIIA (according to the
      Cotswolds modification of the Ann Arbor classsification), whereas advanced HD
      included stage III with B symptoms and stage IV. It was then observed that early
      stage HD with certain clinical risk factors had a significantly worse outcome. As
      a consequence, several studies defined these patients as suffering from early
      stage unfavorable (or intermediate-stage) HD, demanding a more aggressive
      treatment. The treatment of early-stage HD is changing strikingly. Until
      recently, extended-field (EF) irradiation has been considered the standard
      treatment. However, because of the recognition of its high relapse rate and fatal
      long-term effects, EF radiotherapy is now being abandoned by most study groups.
      Instead, for favorable early-stage HD, mild chemotherapy for control of occult
      disease is combined with involved-field (IF) irradiation. In early-stage
      unfavorable (intermediate) HD, four cycles of chemotherapy plus IF irradiation is
      accepted as standard treatment.

PMID- 11296139
TI  - Upfront transplantation for poor-risk aggressive non-Hodgkin lymphoma and
      Hodgkin's disease: who benefits?
AB  - High-dose therapy with autologous stem-cell transplantation is the standard
      treatment for patients with relapsed or primary refractory Hodgkin's disease or
      non-Hodgkin lymphoma. The efficacy of the treatment in this setting has prompted
      extensive investigation of its role in upfront therapy for patients with a poor
      prognosis. Although the preliminary data appear promising, definitive results are
      still lacking, and upfront transplantation remains investigational. Newer
      regimens for the treatment of advanced-stage Hodgkin's disease appear to confer
      cure rates of approximately 85% to 90%. Thus, only a small minority of patients
      may potentially benefit from more aggressive therapy such as upfront
      transplantation. A reliable method of identifying these patients is yet to be
      determined. Upfront transplantation should be evaluated in these patients once
      they are identified.

PMID- 11296141
TI  - Sarcomere length operating range of vertebrate muscles during movement.
AB  - The force generated by skeletal muscle varies with sarcomere length and velocity.
      An understanding of the sarcomere length changes that occur during movement
      provides insights into the physiological importance of this relationship and may
      provide insights into the design of certain muscle/joint combinations. The
      purpose of this review is to summarize and analyze the available literature
      regarding published sarcomere length operating ranges reported for various
      species. Our secondary purpose is to apply analytical techniques to determine
      whether generalizations can be made regarding the "normal" sarcomere length
      operating range of skeletal muscle. The analysis suggests that many muscles
      operate over a narrow range of sarcomere lengths, covering 94+/-13 % of optimal
      sarcomere length. Sarcomere length measurements are found to be systematically
      influenced by the rigor state and methods used to make these measurements.

PMID- 11296143
TI  - Human papillomaviruses and cervical cancer in Bangkok. I. Risk factors for
      invasive cervical carcinomas with human papillomavirus types 16 and 18 DNA.
AB  - Personal interviews, tests for antibodies to herpes simplex virus type 2,
      Treponema pallidum, and hepatitis B, tests for hepatitis B surface antigen
      (HBsAg), and polymerase chain reaction-based assays for human papillomavirus
      (HPV) DNA in cervical scrapings were obtained from 190 women with squamous cell
      and 42 women with adenomatous cervical carcinoma and from 291 hospitalized
      controls diagnosed in Bangkok, Thailand, between September 1991 and September
      1993. Risk was strongly associated with oncogenic HPV types, with types 16 and 18
      predominating in squamous and adenomatous lesions, respectively. The 126 cases
      with HPV-16 and the 42 cases with HPV-18 were compared with 250 controls with no
      evidence of any HPV. The risk of both viral tumor types increased with decreasing
      age at first intercourse in this predominantly monogamous population, which may
      be explained by more visits to prostitutes by the husbands of cases with early
      than late age at first intercourse. HPV-16 tumors were weakly associated with
      HBsAg carrier state and smoking. The risk of tumors of both viral types increased
      with parity and use of oral contraceptives but not with injectable progestogens.
      Factors that may predispose to persistent, oncogenic HPV-16 or -18 infection may
      include estrogens or progestins in the presence of estrogens, immunosuppression,
      and smoking, but other factors related to low socioeconomic status are also
      involved.

PMID- 11296144
TI  - Human papillomaviruses and cervical cancer in Bangkok. II. Risk factors for in
      situ and invasive squamous cell cervical carcinomas.
AB  - To identify risk factors for progression of intraepithelial cervical lesions, 190
      women with invasive cervical cancer were compared with 75 women with in situ
      disease diagnosed in Bangkok, Thailand, between September 1991 and September
      1993. Polymerase chain reaction-based assays for type-specific human
      papillomavirus (HPV) DNA in cervical scrapings revealed oncogenic types in 79% of
      invasive and 57% of intraepithelial tumors. Types 16 and 18, but not types
      31/33/35/39, were more common in invasive than intraepithelial tumors, and
      untyped HPV DNA was found more commonly in the in situ lesions, suggesting that
      in situ disease is four times more likely to become invasive if due to type 16 or
      18 than to other causes, and that tumors with only untyped HPV are not at
      increased risk of progression. After controlling for HPV type, the risk of
      developing invasive diseases, compared with the risk of developing
      intraepithelial lesions, was not related to any of a large number of sexual and
      hormonal factors considered or to smoking, suggesting that any cofactors these
      variables represent act before the development of in situ carcinoma. Two indices
      of socioeconomic status were associated with a reduced risk of only invasive
      disease, suggesting the existence of unknown protective factors that operate
      after intraepithelial lesions develop.

PMID- 11296145
TI  - Human papillomaviruses and cervical cancer in Bangkok. III. The role of husbands
      and commercial sex workers.
AB  - Between September 1991 and September 1993, husbands of women with and without
      cervical neoplasia and commercial sex workers in one brothel and one massage
      parlor in Bangkok, Thailand, were interviewed; serologic tests for sexually
      transmitted infections were performed; and cervical and penile scrapings were
      tested for human papillomavirus (HPV) DNA. The risks of cervical carcinoma in
      monogamous women and of oncogenic HPV in their husbands were associated with the
      men's having unprotected intercourse with prostitutes. The prevalence of
      oncogenic HPV was higher in commercial sex workers than in women attending
      gynecologic and family planning clinics. Oncogenic HPV prevalence declined with
      age in human immunodeficiency virus (HIV)-negative, but not in healthy HIV
      positive, commercial sex workers and was weakly associated with hepatitis B
      antigenemia, suggesting that persistence of HPV infection is due to subtle
      changes in immunity. Associations of HPV with recent pregnancy and oral
      contraceptive use suggest that hormonal factors may increase the risk of cervical
      neoplasia by enhancing persistence of HPV infection. The prevalence of high-grade
      squamous intraepithelial lesions was strongly related to oncogenic HPV types and
      weakly to HIV infection only in their presence. Commercial sex workers in Bangkok
      are reservoirs of oncogenic HPV, and cervical cancer in monogamous Thai women
      develops in part as a result of transmission of these viruses to them by their
      husbands from prostitutes.

PMID- 11296146
TI  - Cancer incidence after childhood nasopharyngeal radium irradiation: a follow-up
      study in Washington County, Maryland.
AB  - A population from a hearing clinic in Washington County, Maryland, in 1943-1960
      was followed to assess the risk of developing neoplasms from radium treatment of
      the nasopharynx for adenoid hypertrophy. Of the 2,925 subjects who attended the
      clinic, 904 received radium treatment. A nonconcurrent prospective study compared
      the cancer incidence among the irradiated persons with that among persons with
      other treatments. Seven brain tumor cases (three malignant and four benign) were
      identified in the irradiated group versus none in the nonirradiated group
      (relative risk = 14.8, 95% confidence interval: 0.76, 286.3). A nonsignificant
      excess risk of thyroid cancer was detected in the irradiated group based on two
      cases in the exposed group and one case in the nonexposed group (relative risk =
      4.2, 95% confidence interval: 0.38, 46.6). Decreased risks of breast cancer,
      female genital cancers, and prostate cancer were observed among the irradiated
      individuals, although these deficits were not statistically significant
      individually. The decreased risk of sex hormone-related cancers in the irradiated
      group suggests possible radiation damage to the pituitary, with consequent
      reduction in pituitary hormone output and alterations in sexual and other
      hormonal development in early life. This hypothesis needs further evaluation.

PMID- 11296147
TI  - Extroversion and neuroticism and the associated risk of cancer: A Danish cohort
      study.
AB  - The authors have investigated the effect of personality, as measured with the
      Eysenck Personality Inventory, on the incidence of cancer among 1,031 persons
      participating in a Danish health survey in 1976-1977 and followed up for 20
      years. They thereby accrued a total of 19,993 person-years. The expected number
      of cancer cases was estimated on the basis of age-, sex-, and site-specific
      incidence rates in Copenhagen County, DENMARK: Overall, 113 malignancies were
      observed among the cohort members between the date of interview and December 31,
      1996. Since 114.3 were expected from county incidence rates, the standardized
      incidence ratio was 0.99 (95% confidence interval: 0.81, 1.19). No statistically
      significant deviation of the relative risk from unity was seen for any measure of
      personality, and no excess risk was seen for any particular type of cancer. A
      regression model, in which adjustment was made for age, sex, calendar period,
      alcohol consumption, tobacco smoking, psychiatric illness as rated by the
      interviewing doctor, marital status, and social class, showed no excess risk of
      cancer among persons considered to be in medium- or high-risk groups according to
      the Eysenck Personality INVENTORY: The authors' data provide no support for the
      hypothesis of an association between personality and the risk of cancer.

PMID- 11296148
TI  - Prevalence and incidence of hepatitis C virus infection in the US military: a
      seroepidemiologic survey of 21,000 troops.
AB  - Because of a high prevalence of hepatitis C virus (HCV) infection (10-20%) among
      veterans seeking care in Department of Veterans Affairs (VA) hospitals, current
      US military forces were evaluated for HCV infection. Banked serum samples were
      randomly selected from military personnel serving in 1997 and were tested for
      antibody to HCV (anti-HCV). Overall prevalence of anti-HCV among 10,000 active
      duty personnel was 0.48% (5/1,000 troops); prevalence increased with age from
      0.1% among military recruits and active-duty personnel aged <30 years to 3.0%
      among troops aged >/=40 years. Prevalence among 2,000 Reservists and active-duty
      troops was similar. Based on sequential serum samples from 7,368 active-duty
      personnel (34,020 person-years of observation), annual incidence of infection was
      2/10,000. Of 81 HCV RNA-positive troops for whom genotype was determined,
      genotypes 1a (63%) and 1b (22%) predominated, as in the civilian population.
      These data indicate that HCV infection risk among current military forces is
      lower than in VA studies and the general civilian population aged <40 years. The
      low level of HCV infection may be attributed to infrequent injection drug use in
      the military due to mandatory testing for illicit drugs prior to induction and
      throughout military service.

PMID- 11296149
TI  - Placental abruption among singleton and twin births in the United States: risk
      factor profiles.
AB  - The authors performed a population-based epidemiologic study to evaluate and
      contrast risk factor profiles for placental abruption among singleton and twin
      gestations. Data were derived from linked US birth/infant death files for 1995
      and 1996, comprising 7,465,858 singleton births and 193,266 twin births. The
      authors also evaluated effect modification between smoking and hypertension and
      the effect of a dose-response relation with number of cigarettes smoked daily on
      abruption risk. Abruption was recorded in 5.9 per 1,000 singleton births and 12.2
      per 1,000 twin births. Risk factors for abruption among singleton and twin
      births, respectively, included preterm premature rupture of membranes (adjusted
      relative risks (RRs) = 4.89 and 2.01), eclampsia (RRs = 3.58 and 1.67), anemia
      (RRs = 2.23 and 2.33), hydramnios (RRs = 2.04 and 1.66), renal disorders (RRs =
      1.54 and 2.56), and intrapartum fever (>100 degrees F) (RRs = 1.17 and 1.69).
      Chronic hypertension (RR = 2.38) and pregnancy-induced hypertension (RR = 2.34)
      were risk factors for abruption in singleton births but not in twin births.
      Number of cigarettes smoked daily demonstrated a dose-response trend for
      abruption risk in singletons and twins. Abruption was more likely to occur among
      smokers with chronic hypertension (RRs = 4.66 and 3.15) and eclampsia (RRs = 6.28
      and 5.08). The authors conclude that abruption is twice as likely to occur in
      twins as in singletons with differing risk factor profiles. This suggests that
      abruption in twins may result from different pathophysiologic processes.

PMID- 11296150
TI  - Differences in birth weight and blood pressure at age 7 years among twins.
AB  - Blood pressure later in life has been inversely associated with birth weight.
      However, concerns have been raised about whether this association merely reflects
      common environmental risk factors for both fetal growth restriction and high
      blood pressure or whether there is a genetic tendency to give birth to small
      babies and have high blood pressure. This study examined whether difference in
      birth weight of twins is associated with difference in blood pressure at age 7
      years. The authors used data from the Collaborative Perinatal Project, United
      States, 1959-1966, which included 119 pairs of monozygotic and 86 pairs of same
      sex dizygotic twins. The smaller twin in each pair had an average 300-g lower
      birth weight and was substantially thinner than the larger twin (p < 0.001). At
      age 7 years, body size and blood pressure were similar. Multiple linear
      regression was used to examine the association between difference in birth size
      and difference in blood pressure, adjusting for difference in body weight at age
      7 years. None of the associations was statistically significant, and the
      direction of the associations was inconsistent. Further analyses stratified by
      birth weight, race, and sex revealed a similar, inconsistent pattern. The
      authors' findings fail to support the hypothesis that an unfavorable intrauterine
      environment adversely affects blood pressure in children.

PMID- 11296151
TI  - Birth weight, childhood growth, and cardiovascular disease risk factors in
      Japanese aged 20 years.
AB  - To determine whether birth weight and childhood growth, especially rate of height
      increase, are independently related to major cardiovascular disease risk factors
      in adult life, the authors conducted a 20-year follow-up study in a Japanese
      population, using the record-linkage method. From medical checkup data for babies
      and for residents aged 20 years in Ishikawa, Japan, the authors obtained 20-year
      follow-up data (1985-1994) on 4,626 participants (2,198 men and 2,428 women) born
      in 1965-1974. Using multiple linear regression analysis, the authors estimated
      that a 1-standard-deviation higher birth weight was significantly associated with
      systolic blood pressure that was lower by 1.6 mmHg in men and by 1.0 mmHg in
      women, and with a serum cholesterol level that was lower by 0.07 mmol/liter in
      men and by 0.04 mmol/liter in women, after adjustment for current weight and rate
      of height increase. Moreover, after adjustment for birth weight and current
      weight, a 1-standard-deviation higher rate of height increase from age 3 years to
      age 20 years was significantly associated with systolic blood pressure that was
      lower by 0.7 mmHg in men and by 0.5 mmHg in women, and with serum cholesterol
      that was lower by 0.09 mmol/liter in men and by 0.05 mmol/liter in women. The
      results suggest that lower birth weight and lower rate of height increase during
      childhood are independently associated with increases in blood pressure and serum
      cholesterol in adult life.

PMID- 11296152
TI  - Soy product intake and hot flashes in Japanese women: results from a community
      based prospective study.
AB  - The association between soy product intake and the occurrence of hot flashes was
      examined in a cohort of 1,106 female residents of Takayama, Gifu, JAPAN: The
      women were aged 35-54 years and premenopausal at their entry into the study in
      1992. Diet, including intake of soy products and isoflavones, was assessed by
      means of a validated semiquantitative food frequency questionnaire at study
      entry. A follow-up mail questionnaire asking about experiences of hot flashes was
      sent in 1998. During the 6 years of the study period, 101 women had new moderate
      or severe hot flashes according to the Kupperman test of menopausal distress.
      After data were controlled for age, total energy intake, and menopausal status,
      hot flashes were significantly inversely associated with consumption of soy
      products in terms of both total amount (highest tertile of soy product intake
      (g/day) vs. lowest: hazard ratio = 0.47; 95% confidence interval: 0.28, 0.79; p
      for trend = 0.005) and isoflavone intake (highest tertile of isoflavone intake
      (mg/day) vs. lowest: hazard ratio = 0.42; 95% confidence interval: 0.25, 0.72; p
      for trend = 0.002). These data suggest that consumption of soy products has a
      protective effect against hot flashes.

PMID- 11296153
TI  - Association between HLA-DQB1 alleles and type 1 diabetes in a case-parents study
      conducted in Santiago, Chile.
AB  - The human leukocyte antigen (HLA) system plays a crucial role in the autoimmune
      process leading to childhood diabetes. The purpose of this study was to evaluate
      the association between type 1 diabetes and the polymorphism encoded by the HLA
      DQB1 gene by using case-parents trios. The study area was the metropolitan region
      of Santiago, Chile, and cases were ascertained from March 1997 to August 1998.
      Genotyping was performed in 94 trios comprising incident cases less than 17 years
      of age at the time of diagnosis and their parents. The
      transmission/disequilibrium test was used to detect differential transmission in
      the HLA-DQB1 locus. The authors found that alleles DQB1(*)0302 and DQB1(*)0201
      were strongly associated with the disease. By using 1:3 matched sets of cases
      pseudosibs and conditional logistic regression models, allelic relative risks
      were estimated for DQB1(*)0302 (r = 7.2, 95% confidence interval: 2.8, 18.5) and
      DQB1(*)0201 (r = 4.7, 95% confidence interval: 1.9, 11.6); DQB1(*)0301 was
      considered the baseline allele. When case-parents trios were used, alleles
      DQB1(*)0302 and DQB1(*)0201 were strongly associated with a higher risk of type 1
      diabetes in the population of SANTIAGO:

PMID- 11296154
TI  - Ethnic differences in fibrinogen levels: the role of environmental factors and
      the beta-fibrinogen gene.
AB  - Fibrinogen is a cardiovascular risk factor, but little is known about levels in
      ethnic groups that differ in their cardiovascular risk. Fibrinogen was measured
      in 479 Black individuals, 459 South Asian Indians, and 453 Whites aged 40-59
      years living in south London, England, from March 1994 to July 1996. Genotype was
      determined at two sites in the promoter of the beta-fibrinogen gene (G-455-->A
      and C-148-->T). Plasma fibrinogen levels were lower in Blacks than in Whites by
      0.22 g/liter (95% confidence interval (CI): 0.08, 0.36) in men and 0.11 g/liter
      (95% CI: -0.01, 0.23) in women. These differences were not explained by measured
      environmental variables, including smoking, or by genotypes. The fibrinogen
      levels of South Asians were not consistently different from those of WHITES: The
      A-455 and T-148 alleles were less common in Blacks than in either Whites or South
      ASIANS: In Whites and South Asians, but not in Blacks, there was complete allelic
      association between the two variants. In Blacks, the T allele rather than the A
      allele was associated with higher fibrinogen levels. The average fibrinogen
      raising effect of the T-148 allele across all ethnic groups was 0.14 g/liter (95%
      CI: 0.02, 0.26 g/liter) in women and 0.15 g/liter (95% CI: 0.03, 0.27 g/liter) in
      men. Low fibrinogen levels in Blacks may partly explain their lower risk of
      ischemic heart disease in the United KINGDOM:

PMID- 11296155
TI  - Factors associated with discrepancies between self-reports on cigarette smoking
      and measured serum cotinine levels among persons aged 17 years or older: Third
      National Health and Nutrition Examination Survey, 1988-1994.
AB  - The discrepancy between cigarette smoking status reported during an interview and
      measured level of serum cotinine, a nicotine biomarker, was investigated in a
      representative sample of the US population aged >/=17 years (N = 15,357). Data
      were collected from participants in the Third National Health and Nutrition
      Examination Survey (1988-1994). Among self-reported smokers, 7.5% (95% confidence
      interval: 6.3, 8.7) had a serum cotinine level less than or equal to 15.0 ng/ml,
      the selected cutoff point for identifying nonsmokers. Age (p < 0.01),
      race/ethnicity (p < 0.01), and average number of cigarettes smoked per day (p <
      0.01) were associated with these discrepant findings. Among self-reported
      nonsmokers, 1.4% (95% confidence interval: 1.1, 1.7) had a serum cotinine level
      greater than 15.0 ng/ml, the selected cutoff point for identifying smokers.
      Race/ethnicity (p < 0.01), education (p < 0.01), number of household members who
      smoked in the home (p = 0.03), and self-reported smoking status from an earlier
      home interview (p < 0.01) were associated with these discrepant findings.
      Differences in smoking patterns, including the extent of nicotine dosing, may
      explain most of the discrepancy observed among self-reported smokers, whereas
      deception regarding smoking status may explain most of the discrepancy among self
      reported nonsmokers. This study provides evidence that self-reported smoking
      status among adult respondents to a population-based survey conducted in a
      private medical setting is accurate.

PMID- 11296156
TI  - Misclassification of exposure: coffee as a surrogate for caffeine intake.
AB  - This study was conducted to assess the effect of exposure misclassification when
      coffee is used as a surrogate measure of caffeine exposure. Subjects were
      randomly selected from the telephone directories of four regional municipalities
      in southern Ontario, CANADA: Data on daily caffeine intake from foods, beverages,
      and medications were collected from June to November 1995 through self
      administered, mailed questionnaires from 481 men and women aged 30-75 years.
      Although coffee was the main source of caffeine, cross-tabulations of exposure to
      coffee by total caffeine intake showed that assessment of coffee alone severely
      underestimated caffeine intake by at least one exposure level. A hypothetical 10
      fold increase in risk was completely obscured when only coffee was used to
      estimate total caffeine intake. The results of this study suggest that measuring
      coffee instead of caffeine intake may contribute to a lack of positive findings
      in studies of coffee as a risk factor for disease occurrence, if in fact caffeine
      is the exposure of interest. On the other hand, measurement of coffee, tea, and
      cola soft drink intake in the present study appeared to approximate caffeine
      intake sufficiently and not affect risk estimates adversely.

PMID- 11296157
TI  - Physician education and the pharmaceutical industry.

PMID- 11296158
TI  - Critical interactions : man and machine.

PMID- 11296159
TI  - Influenza pneumonia in thoracic organ transplant recipients : what can we do to
      avoid it?

PMID- 11296160
TI  - Pulmonary artery catheterization in the ICU/critical care unit : indications and
      contraindications remain objectively undefined.

PMID- 11296161
TI  - Comparisons of peak diurnal expiratory flow variation, postbronchodilator FEV(1)
      responses, and methacholine inhalation challenges in the evaluation of suspected
      asthma.
AB  - STUDY OBJECTIVES: The validity of peak expiratory flow variation (PEFvar) as
      defined by National Heart, Lung, and Blood Institute (NHLBI) guidelines as a
      diagnostic tool for suspected asthma or its comparative value to methacholine
      inhalation challenge (MIC) or postbronchodilator (BD) FEV(1) responses has not
      been formally assessed. We prospectively analyzed the correlation of 28 different
      PEFvar indexes (including 4 NHLBI-compatible indexes) with MIC and pre-BD and
      post-BD FEV(1) responses in suspected asthmatic subjects with normal findings on
      lung examination, chest radiography, and baseline spirometry. DESIGN:
      Participants were asked to record peak expiratory flow four times daily for 2 to
      3 weeks, followed by an MIC. During a minimum 6-month follow-up period, a
      clinical diagnosis of asthma was made or ruled out based on testing results and
      response to antiasthma therapy. SETTING: Medical school-affiliated subspecialty
      private practice of allergy, asthma, and immunology. PARTICIPANTS: One hundred
      twenty-one suspected asthmatic patients with normal findings on lung examination,
      chest radiography, and baseline spirometry. MEASUREMENTS AND RESULTS: Fifty-seven
      subjects completed both the peak flow diary and the MIC and were accepted for
      statistical analysis. There were no statistically significant correlations
      between any peak expiratory flow index and MIC. Among the three diagnostic tools
      evaluated, MIC had the highest sensitivity (85.71%). All the PEFvar indexes and
      post-BD responses had low sensitivity and high false-negative rates. CONCLUSIONS:
      PEFvar and post-BD FEV(1) responses are poor substitutes for MIC in the
      assessment of patients with suspected asthma with normal findings on lung
      examination, chest radiography, and spirometry. Our findings warrant a
      reconsideration of the NHLBI guidelines recommendation of the utility of PEFvar
      as a diagnostic tool for asthma in clinical practice.

PMID- 11296162
TI  - Mild exacerbations and eosinophilic inflammation in patients with stable, well
      controlled asthma after 1 year of follow-up.
AB  - OBJECTIVES: To determine the time to exacerbation and probability of a mild
      exacerbation of asthma, and the impact of eosinophilic inflammation on these
      parameters in patients with stable, well-controlled asthma. PATIENTS AND METHODS:
      A cohort of 31 patients with stable, well-controlled asthma receiving inhaled
      steroid treatment regularly were followed up for 1 year or until a mild
      exacerbation occurred. Mild exacerbation was defined as symptoms of asthma
      lasting > 48 h with a fall in peak expiratory flow > 20%. FEV(1), provocative
      concentration of methacholine causing a 20% fall in FEV(1), eosinophil count, and
      eosinophilic cationic protein (ECP) levels in blood and in sputum were measured
      at the first visit and every 2 months. RESULTS: At baseline, the mean (SD)
      eosinophil count was 0.39 x 10(9)/L (0.21 x 10(9)/L) in blood and 13% (14%) in
      sputum; ECP was 30 microg/L (28 microg/L) in blood and 75 microg/L (85 microg/L)
      in sputum. Thirteen subjects experienced a mild exacerbation during the 1-year
      follow-up period. The mean time to mild exacerbation was 293 days (95% confidence
      interval [CI], 248 to 337 days), and the cumulative probability of not
      experiencing a mild exacerbation in 1 year was 49% (95% CI, 39 to 59%). An
      increased risk of mild exacerbation was associated with blood eosinophil count >
      0.4 x 10(9)/L (relative risk 4.5; 95% CI of relative risk, 1.8 to 38.0), blood
      ECP > 20 microg/L (relative risk, 2.1; 95% CI of relative risk, 1.0 to 9.2), and
      sputum ECP > 40 microg/L (relative risk, 2.5; 95% CI of relative risk, 1.2 to
      11.2), but was unassociated with other variables. CONCLUSIONS: Patient with
      stable, well-controlled asthma are at risk of mild exacerbation during 1 year of
      follow-up despite regular inhaled steroid treatment. Eosinophilic inflammation
      expressed as eosinophil count and ECP is associated with higher risk of mild
      exacerbation.

PMID- 11296163
TI  - Comparative in vivo lung delivery of hydrofluoroalkane-salbutamol formulation via
      metered-dose inhaler alone, with plastic spacer, or with cardboard tube.
AB  - STUDY OBJECTIVE: To compare the lung delivery of chlorofluorocarbon-free
      salbutamol via a pressurized metered-dose inhaler (pMDI) alone, a pMDI with a
      small-volume plastic spacer, and a pMDI with a cardboard tube. DESIGN: A
      randomized, single (investigator)-blind, three-way, crossover study. SETTING: The
      Asthma and Allergy Research Group, Ninewells Hospital, University of Dundee,
      Dundee, Scotland, UK. PARTICIPANTS: Twelve healthy volunteers aged 16 to 65
      years. INTERVENTIONS: The subjects were administered 400 microg of salbutamol via
      a pMDI alone, via a pMDI plus a small-volume plastic spacer, or via a pMDI plus a
      cardboard tube. MEASUREMENTS AND RESULTS: Blood samples for plasma salbutamol
      concentrations were taken at 5 min, 10 min, and 20 min after inhalation, to
      measure lung bioavailability as a surrogate for relative lung dose. The addition
      of the plastic spacer resulted in a significantly higher maximal plasma
      salbutamol concentration (CMAX) and average plasma salbutamol concentration (CAV)
      than the pMDI used alone. This amounted to a 1.48-fold (32%) difference (95%
      confidence interval [CI], 1.03 to 2.13) for CMAX and a 1.42-fold (30%) difference
      (95% CI, 1.01 to 2.00) for CAV. There was no significant difference in the CMAX
      or CAV comparing the addition of the cardboard tube with the plastic spacer or
      the pMDI alone. CONCLUSIONS: Using a chlorofluorocarbon-free pMDI with a plastic
      spacer produced statistically, but not biologically, significant greater lung
      delivery of salbutamol. If a spacer is required for reasons other than increasing
      delivered drug dose, then the addition of a readily available cardboard tube will
      fulfill many of the required functions with no expense to the patient.

PMID- 11296164
TI  - Evaluation of salmeterol or montelukast as second-line therapy for asthma not
      controlled with inhaled corticosteroids.
AB  - OBJECTIVE: To assess the addition of a leukotriene receptor antagonist and a long
      acting beta(2)-agonist as second-line therapy in asthma. DESIGN: Placebo
      controlled, double-dummy, crossover study. SETTING: Outpatient clinic. PATIENTS:
      Twenty patients with persistent asthma not controlled with inhaled corticosteroid
      therapy. INTERVENTIONS: Montelukast 10 mg once daily, or salmeterol, 50 microg
      bid, each for 2 weeks with 1-week run-in and washout placebo periods.
      MEASUREMENTS AND RESULTS: Adenosine monophosphate (AMP) bronchial challenge,
      blood eosinophil count (EOS), exhaled nitric oxide, and lung function after both
      placebo periods and after the first and last doses of each active treatment.
      Patients recorded their domiciliary peak expiratory flow (PEF), asthma symptoms,
      and rescue bronchodilator requirement (RES) twice daily throughout the study. For
      the primary end point of the provocative concentration of AMP causing a 20% fall
      in FEV(1), compared to placebo (47.5 +/- 13.0 mg/mL), there were significant
      differences with the first (114.1 +/- 36.9 mg/mL) and last (94.2 +/- 30.4 mg/mL)
      doses of montelukast as well as the first (160.1 +/- 64.5 mg/mL) but not the last
      (70.1 +/- 23.7 mg/mL) dose of salmeterol. Only montelukast produced significant
      suppression of the EOS. Neither drug affected exhaled nitric oxide levels. There
      were significant improvements with the first doses of salmeterol for all
      parameters of lung function. After 2 weeks of treatment, there were significant
      improvements with both drugs for RES and morning PEF. There were no significant
      differences between drugs for any end points except EOS. CONCLUSIONS: Montelukast
      and salmeterol exhibited significant improvements in asthma control when given as
      second-line therapy. Montelukast also produced significant effects on AMP
      challenge and EOS suggesting anti-inflammatory activity.

PMID- 11296165
TI  - The utility of peak flow, symptom scores, and beta-agonist use as outcome
      measures in asthma clinical research.
AB  - STUDY OBJECTIVES: Several methods of utilizing peak expiratory flow (PEF) and
      other markers of disease activity have been suggested as useful in the management
      of asthma. It remains unclear, however, as to which surrogate markers of disease
      status are discriminative indicators of treatment failure, suitable for use in
      clinical trials. DESIGN: We analyzed the operating characteristics of 66
      surrogate markers of treatment failure using a receiver operating characteristic
      (ROC) curve analysis. PARTICIPANTS: Information regarding FEV(1), symptoms,
      beta(2)-agonist use, and PEF was available from 313 subjects previously enrolled
      in two Asthma Clinical Research Network trials, in which 71 treatment failures
      occurred (defined by a 20% fall in FEV(1) from baseline). INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: None of the measures had an acceptable ability to
      discriminate subjects with a > or % fall in FEV(1) from those without, regardless
      of the duration of the period of analysis or the criteria for test positivity
      employed. Areas under the ROC curves generated ranged from 0.51 to 0.79, but none
      were statistically superior. Sensitivity and specificity combinations were
      generally poor at all cutoff values; true-positive rates could not be raised
      without unacceptably elevating false-positive rates concurrently. CONCLUSIONS:
      Studies that seek to detect treatment failure defined by a significant fall in
      FEV(1) should not use such individual surrogate measures to estimate disease
      severity.

PMID- 11296166
TI  - Determinants of different dimensions of disease severity in asthma and COPD :
      pulmonary function and health-related quality of life.
AB  - OBJECTIVE: To identify determinants of pulmonary function and health-related
      quality of life (HRQOL) to better understand disease severity in patients with
      asthma and COPD. DESIGN: Observational study. SETTING: Dutch general practice.
      PATIENTS: We studied 837 asthma patients and 231 COPD patients. RESULTS: The
      association between pulmonary function and HRQOL was poor for asthma (beta =
      0.10) and COPD (beta = 0.19). Multivariately, in asthma, lower pulmonary function
      was associated with male gender, region of living, current smoking, use of
      inhaled short-acting bronchodilators, longer duration of disease, and higher
      diurnal variation in peak expiratory flow. In COPD, lower pulmonary function was
      associated with male gender, use of inhaled bronchodilators, more days and nights
      disturbed by respiratory complaints, not wheezing, and bronchial
      hyperresponsiveness. Reduced HRQOL was associated most strongly with more days
      and nights disturbed by respiratory complaints and dyspnea in both asthma and
      COPD. In asthma, additional associations were found with younger age, lower
      educational level, region of living, comorbidity, use of inhaled bronchodilators
      and corticosteroids, wheezing, chronic cough, sputum production, and bronchial
      hyperresponsiveness. In COPD, lower age, not smoking, chronic cough, and sputum
      production were associated with reduced HRQOL. CONCLUSIONS: Pulmonary function
      and HRQOL appear to highlight different aspects of disease severity in asthma and
      COPD. Therefore, both measures should be taken into account in order to get a
      complete picture of severity of disease.

PMID- 11296167
TI  - Increased prevalence of gastroesophageal reflux symptoms in patients with COPD.
AB  - STUDY OBJECTIVES: To determine the prevalence of gastroesophageal reflux (GER)
      symptoms in patients with COPD and the association of GER symptoms with the
      severity of airways obstruction as assessed by pulmonary function tests (PFTs).
      DESIGN: Prospective questionnaire-based, cross-sectional analytic survey.
      SETTING: Outpatient pulmonary and general medicine clinics at a Veterans
      Administration hospital. PATIENTS: Patients with mild-to-severe COPD (n = 100)
      were defined based on American Thoracic Society criteria. The control group (n =
      51) consisted of patients in the general medicine clinic without respiratory
      complaints or prior diagnosis of asthma or COPD. INTERVENTION: Both groups
      completed a modified version of the Mayo Clinic GER questionnaire. RESULTS:
      Compared to control subjects, a greater proportion of COPD patients had
      significant GER symptoms defined as heartburn and/or regurgitation once or more
      per week (19% vs 0%, respectively; p < 0.001), chronic cough (32% vs 16%; p =
      0.03), and dysphagia (17% vs 4%; p = 0.02). Among patients with COPD and
      significant GER symptoms, 26% reported respiratory symptoms associated with
      reflux events, whereas control subjects denied an association. Significant GER
      symptoms were more prevalent in COPD patients with FEV(1) < or %, as compared
      with patients with FEV(1) > 50% of predicted (23% vs 9%, respectively; p = 0.08).
      In contrast, PFT results were similar among COPD patients with and without GER
      symptoms. An increased number of patients with COPD utilized antireflux
      medications, compared to control subjects (50% vs 27%, respectively; p = 0.008).
      CONCLUSIONS: The questionnaire demonstrated a higher prevalence of weekly GER
      symptoms in patients with COPD, as compared to control subjects. There was a
      trend toward higher prevalence of GER symptoms in patients with severe COPD;
      however, this difference did not reach statistical significance. We speculate
      that although GER may not worsen pulmonary function, greater expiratory airflow
      limitation may worsen GER symptoms in patients with COPD.

PMID- 11296168
TI  - Exhaled nitric oxide correlated with induced sputum findings in COPD.
AB  - STUDY OBJECTIVES: Neutrophilic airway inflammation may underlie the pathogenesis
      of COPD. We examined repeated measurements of the fractional concentration of
      exhaled nitric oxide (FENO) and the correlation with cells and mediators in
      induced sputum (IS) from patients with COPD. PARTICIPANTS: Eleven COPD subjects
      (9 men and 2 women, aged 46 to 69 years) with predicted FEV(1) of 45 to 70%.
      SETTING: A hospital research laboratory. DESIGN: Single-cohort, prospective study
      with four visits at two weekly intervals. INTERVENTIONS: FENO and spirometry were
      assessed at all visits, and IS for differential cell count, leukotriene-B(4)
      (LTB(4)) and interleukin (IL)-8, nitrite, and nitrate at visit 1, visit 3, and
      visit 4. RESULTS: During the study, there were significant declines in mean
      percent predicted FEV(1), from 55.2 to 51.6% (p = 0.029), and mean FEV(1)/FVC
      ratio, from 50.4 to 45.4% (p = 0.001), accompanied by a significant increase in
      FENO geometric mean (95% confidence limits), from 15.2 (10.9 to 21.2) to 23.6
      (17.1 to 32.4) parts per billion (p = 0.037), and sputum LTB(4), from 1.79 (1.03
      to 3.11) to 3.57 (1.95 to 6.53) ng/mL (p = 0.033), but no significant change in
      other sputum parameters. From visits 1 to 4, the change in percent neutrophils
      correlated with the changes in FENO and IL-8 (r = 0.648, p = 0.028; r = 0.60, p =
      0.05, respectively). Hypertonic saline solution induction of sputum caused a fall
      in FEV(1), from 1.83 +/- 0.44 to 1.46 +/- 0.44 L (p = 0.049). CONCLUSIONS: The
      worsening spirometry results were accompanied by significant increases in FENO
      and sputum LTB(4). FENO may be related to neutrophilic inflammation driven by the
      chemoattractant IL-8. FENO and IS may be useful markers of airway inflammation in
      COPD patients. Sputum induction with hypertonic saline solution causes a
      significant fall in FEV(1) requiring appropriate caution.

PMID- 11296169
TI  - Underestimation of mortality following lung volume reduction surgery resulting
      from incomplete follow-up.
AB  - STUDY OBJECTIVES: Incomplete follow-up can bias interpretation of data that are
      collected in longitudinal studies. We noted that many patients failed to return
      for follow-up in a study of effect of lung volume reduction surgery (LVRS) on
      quality of life (QOL). Accordingly, we designed this investigation to determine
      the reasons patients dropped out, and to assess differences between those who
      continued in the study (attendees) and those who did not (nonattendees). DESIGN:
      Telephone survey. SUBJECTS: Patients with advanced emphysema who had undergone
      LVRS and had previously agreed to participate in a longitudinal QOL study.
      RESULTS: No differences were found with regard to age, gender, preoperative
      pulmonary function, or oxygen use between attendees and nonattendees. Long-term
      mortality in nonattendees (27%) was considerably greater than that seen in
      attendees (3%, p < 0.05). Distance from the hospital, financial burden, and
      living out of the region were the most common reasons cited by surviving
      nonattendees for their failure to return for follow-up. CONCLUSIONS: Studies
      reporting the long-term mortality after LVRS can be biased in the direction of
      underestimating the true value if they are compromised by incomplete follow-up.

PMID- 11296170
TI  - Effect of ischemic preconditioning on myocardial protection in coronary artery
      bypass graft patients : can the free radicals act as a trigger for ischemic
      preconditioning?
AB  - OBJECTIVE: To investigate the interrelationship of free radicals (FRs), ischemic
      preconditioning (IP), and hemodynamic function in coronary artery bypass graft
      (CABG) patients. DESIGN: Prospective, randomized, and controlled clinical study.
      PATIENTS: Forty CABG patients were randomized into an IP group (n = 20) and a
      control group (n = 20). INTERVENTION: The IP group was preconditioned with two
      cycles of two-min ischemia followed by 3-min reperfusion before cross-clamping.
      MEASUREMENT AND RESULTS: FR content in coronary sinus blood was measured directly
      using alpha-phenyl-N-tert-butylnitrone-electron spin-trapped spectroscopy. A
      small amount of FRs was generated after the IP protocol (5.6% above the baseline)
      but not in control subjects. A larger amount was generated 10 min after
      declamping in both groups (8.4% in IP protocol and 7.7% in control subjects).
      Hemodynamic function recovered better in the IP group at 1 h and 6 h after
      declamping. There was a significant negative correlation between FR generation
      after declamping and left ventricular stroke work index (LVSWI) at 1 h and 6 h
      after declamping (r = -0.71 and - 0.59, respectively) in the control subjects but
      not in the IP group. There was a significant positive correlation between FR
      generation after the IP protocol and cardiac index at 1 h and 6 h (r = 0.50 and
      0.61, respectively) and LVSWI at 1 h and 6 h (r = 0.56 and 0.54, respectively)
      after declamping in the IP group but not in the control subjects. CONCLUSION: FR
      generation after the operation correlates with ventricular functional depression
      in CABG patients. IP protects the stunning heart but does not alter FR
      generation. The association of better hemodynamic recovery after CABG with FR
      generation during the IP period suggests that FRs might act as one of the
      triggers for IP.

PMID- 11296171
TI  - Pulmonary resection for metastases from colorectal cancer.
AB  - BACKGROUND: We reviewed our experience in the surgical treatment of 47 patients
      with colorectal pulmonary metastases and investigated factors affecting their
      survival. METHOD: From September 1986 to December 1999, 47 patients underwent 59
      thoracotomies for pulmonary metastases from colorectal cancer. RESULTS: The
      median interval between colorectal resection and lung resection (disease-free
      interval [DFI]) was 33 months. Overall, 5-year survival was 48%. Five-year
      survival was 51% for patients with solitary metastasis (n = 30), 47% for patients
      with ipsilateral multiple metastases (n = 11), and 50% for patients with
      bilateral metastases (n = 6), and there were no significant differences. Five
      year survival was 80.8% for 14 patients with DFI of < 2 years and 39.7% for 30
      patients with a DFI of > 2 years (p = 0.22). Five-year survival for 11 patients
      with normal prethoracotomy carcinoembryonic antigen (CEA) levels was 70%, and
      that for 26 patients with elevated prethoracotomy CEA levels (> 5 ng/mL) was 36%
      (p < 0.05). Eight patients had extrathoracic disease. The median survival time
      after pulmonary resection was 18.5 months, and the 5-year survival was 60%. A
      second resection for recurrent metastases was performed in five patients, and a
      third resection was done in one patient. All six patients are alive. The median
      survival of five patients who underwent a second thoracotomy was 22 months
      (range, 2 to 68 months), and one patient is alive 39 months after the third
      resection. CONCLUSION: Pulmonary resection for metastases from colorectal cancer
      may help prolong survival in selected patients, even with bilateral lesions,
      recurrent metastasectomy, or extrathoracic disease. Prethoracotomy CEA level was
      found to be a significant prognostic factor.

PMID- 11296172
TI  - Prolonged oxygen kinetics during early recovery from maximal exercise in adult
      patients with cystic fibrosis.
AB  - STUDY OBJECTIVES: To explore the significance of oxygen kinetics during early
      recovery after maximal cardiopulmonary exercise testing (CPET) in the assessment
      of functional capacity and severity of the disease in cystic fibrosis (CF)
      patients. PARTICIPANTS: Eighteen patients with CF (9 male/9 female; mean +/- SD
      age, 23 +/- 13 years) and 11 healthy subjects (3 male/8 female; mean age, 29 +/-
      4 years) underwent maximum CPET on a treadmill. Breath-by-breath analysis was
      used for measuring oxygen consumption (VO(2)), carbon dioxide production, and
      ventilation. Maximum VO(2) (VO(2)peak) and the first-degree slope of VO(2)
      decline during early recovery (VO(2)/t-slope) were calculated. To assess the
      severity of the disease, we used standard indexes like FEV(1) (% predicted),
      VO(2)peak, and a widely accepted system of clinical evaluation, the Schwachman
      score (SS). RESULTS: VO(2)/t-slope was significantly lower in CF patients
      compared to healthy subjects (0.61 +/- 0.31 L/min/min vs 1.1 +/- 0.13 L/min/min;
      p < 0.01) and was closely correlated to FEV(1)(r = 0.90, p < 0.001), VO(2)peak (r
      = 0.81, p < 0.001), and the SS (r = 0.81, p < 0.001). The multivariate analysis
      showed that the only independent predictor of the SS is the VO(2)/t-slope.
      CONCLUSION: We conclude that in CF patients, the prolonged oxygen kinetics during
      early recovery from maximal exercise is related to the disease severity.

PMID- 11296173
TI  - Psychological functioning of adults with cystic fibrosis.
AB  - STUDY OBJECTIVES: The purpose of this study is to assess the psychological
      profiles of adult patients with cystic fibrosis (CF) and to investigate
      predictors of patients' psychological status. PATIENTS AND METHODS: Thirty-four
      adults with CF completed a battery of psychological testing including the
      Minnesota Multiphasic Personality Inventory-2, Beck Depression Inventory, and
      State-Trait Anxiety inventory. These were compared to health status data,
      including pulmonary function testing and nutritional status measures. RESULTS: As
      a group, adults with CF did not demonstrate significant levels of depression,
      anxiety, or other psychopathology. Results were not affected by age, sex, or
      severity of disease. Male gender predicted higher scores for depression and
      anxiety, and better lung functioning predicted less anxiety. Having a higher
      level of psychosocial support emerged as a strong predictor of better
      psychological functioning. CONCLUSIONS: Overall, adults with CF report relatively
      healthy psychological functioning. Better lung function and a strong social
      support system predicted better psychological functioning, which may have
      implications for clinical intervention.

PMID- 11296174
TI  - Impairment of vascular endothelial function and left ventricular filling :
      association with the severity of apnea-induced hypoxemia during sleep.
AB  - STUDY OBJECTIVE: To investigate whether a dose-effect relationship exists between
      the severity of obstructive sleep apnea (OSA) and subclinical indicators of
      myocardial or vascular dysfunction. DESIGN: Cross-sectional study using
      correlation analysis. PARTICIPANTS: Twenty subjects referred to our sleep
      laboratory for screening or therapy of OSA but without regular medication and
      without known cardiovascular disease. MEASUREMENTS: Severity of OSA was
      quantified by polysomnography. Moreover, nocturnal excretion of norepinephrine
      was determined. Left ventricular (LV) myocardial function was assessed with
      Doppler echocardiography. Using ultrasonographic measurements, endothelium
      dependent and endothelium-independent conduit artery dilation were measured as
      flow-mediated and glyceryltrinitrate-induced changes in brachial artery diameter.
      RESULTS: Worsening nocturnal hypoxemia, measured as nocturnal oxygen saturation
      nadir or percentage of sleep time spent in hypoxemia (< 90% hemoglobin oxygen
      saturation), predicted increased interventricular septum thickness (corrected for
      age and body mass index), prolonged isovolumetric relaxation time, decreased
      ratio between peak early and late mitral flow velocities, as well as reduced
      endothelium-dependent dilatory capacity of the brachial artery (all relationships
      corrected for cofactor age and with p < 0.05) were observed. Associations between
      these cardiovascular function markers and nocturnal excretion of norepinephrine
      followed the same trend, but relations with interventricular septum thickness and
      flow-mediated artery dilation missed significance (p = 0.064 and p = 0.061,
      respectively). LV posterior wall thickness, measures of LV systolic function,
      early mitral flow deceleration time, and endothelium-independent artery dilation
      were not significantly related to the degree of nocturnal hypoxemia or
      norepinephrine excretion. None of the correlations with apnea-hypopnea index were
      statistically significant. CONCLUSIONS: The severity of apnea-related hypoxemia
      is associated with a gradual deterioration of LV diastolic function as well as
      large-artery endothelial function.

PMID- 11296175
TI  - Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic
      responses to a laboratory stressor in apneic patients.
AB  - OBJECTIVES: We examined the effect of continuous positive airway pressure (CPAP)
      treatment for sleep apnea on cardiac contractility, heart rate variability, and
      hemodynamics at rest and in response to a laboratory stressor. SUBJECTS AND
      INSTRUMENTATION: Forty-one apneic patients were studied on three occasions:
      before treatment, after 1 full night of CPAP treatment, and after 1 week of CPAP
      treatment. The subjects were randomly assigned to receive effective treatment or
      placebo. Contractility and hemodynamics were determined with impedance
      cardiography, and parasympathetic activity was assessed by analysis of heart rate
      variability. Measures were determined at rest and in response to a stressor.
      DESIGN AND RESULTS: For the cardiac sympathetic (contractility) measures
      (preejection period, cardiac acceleration index [CAI], and low-frequency/high
      frequency ratio) significant interactions were found in the combination treatment
      (CPAP vs placebo) by study day (day 1, day 3, day 11) by test period (baseline,
      preparation, talking) [p < 0.01]. For these measures, there were no differences
      between the treatment groups or responses to the stressor on day 1. Levels in
      placebo-treated subjects did not change or respond on the subsequent study days.
      In the CPAP-treated subjects, there was a decrease in these indexes at baseline,
      which became significantly lower by day 11 (ie, CAI levels were 24 Omega/s(2), 22
      Omega/s(2), and 14 Omega/s(2) on day 1, day 3, and day 11, respectively). These
      measures also became responsive to the stressor by showing increased sympathetic
      activity (CAI levels on day 11 were 14 Omega/s(2) at baseline, 32 Omega/s(2)
      during speech preparation, and 36 Omega/s(2) while speaking). The parasympathetic
      indexes, such as high-frequency power or band of heart rate variability as
      determined by spectral analysis, showed a significant day-by-treatment
      interaction (p < 0.005), whereas the CPAP- treated group had significantly more
      parasympathetic activity after 1 week of treatment. For the hemodynamic measures
      (stroke volume [SV], cardiac output, and systemic vascular resistance [SVR]),
      there were significant treatment-by-study day-by-test-period interactions (p <
      0.01). SV and cardiac output increased across days, and SVR decreased in the CPAP
      treated patients. CONCLUSIONS: These results indicate that CPAP normalizes
      contractility, increases cardiac vagal tone, and changes hemodynamic regulation
      from being resistance dominated to being cardiac dominated. Thus, after 1 week of
      treatment with CPAP, many of the indicators of poor cardiac functioning in apnea
      patients are improved.

PMID- 11296176
TI  - The obesity hypoventilation syndrome can be treated with noninvasive mechanical
      ventilation.
AB  - STUDY OBJECTIVES: To assess the effectiveness of nasal noninvasive mechanical
      ventilation (NIMV) in patients with obesity hypoventilation syndrome (OHS).
      DESIGN: Clinical assay that compares two groups of patients with hypercapnic
      respiratory failure, one group with OHS and the other group with kyphoscoliosis,
      in their basal situation and after 4 months of treatment with nocturnal NIMV.
      Thirty-six patients (22 patients with OHS and 14 patients with kyphoscoliosis)
      completed the study protocol. RESULTS: The frequency of symptoms, such as morning
      headache, morning drowsiness, dyspnea, and leg edema, improved in a statistically
      significant way in both groups of patients. The sleepiness improved only in the
      group with OHS. The comparison of frequency of symptoms between both groups of
      patients after NIMV treatment did not present statistically significant
      differences. In the resting situation and without nasal ventilation in place, the
      PO(2) (mean +/- SD) changed from 51 +/- 10 to 64 +/- 11 mm Hg (p < 0.001) and
      PCO(2) from 58 +/- 10 to 45 +/- 5 mm Hg (p < 0.001) when the patients with OHS
      were treated with NIMV. In the group of patients with kyphoscoliosis, likewise
      without nasal ventilation in place, PO(2) changed from 53 +/- 6 to 65 +/- 5 mm Hg
      (p < 0.001) and PCO(2) from 59 +/- 11 to 45 +/- 4 mm Hg (p < 0.001) with NIMV
      treatment. When we compared PO(2) and PCO(2) in both groups of patients at the
      beginning and at the end of NIMV treatment, we did not find statistically
      significant differences between OHS and kyphoscoliosis. CONCLUSIONS: NIMV
      improves the clinical symptoms and the respiratory failure of patients with OHS
      to a similar degree to that reported for diseases in which its use is completely
      established, such as kyphoscoliosis. Therefore, NIMV could be an alternative to
      the treatment of patients with OHS.

PMID- 11296177
TI  - Assessing inspiratory muscle strength in patients with neurologic and
      neuromuscular diseases : comparative evaluation of two noninvasive techniques.
AB  - STUDY OBJECTIVES: Static mouth pressure during maximal inspiratory efforts is
      commonly used to evaluate inspiratory muscle strength. However, maximal
      inspiratory pressure (MIP) presents some potential limitations likely to be
      overcome by the measure of mouth pressure during a maximal sniff maneuver in
      patients with respiratory muscle weakness. The aim of the present study was to
      assess whether mouth pressure during sniff maneuver (Pmosn) is a better index of
      inspiratory muscle strength than MIP in patients with neurologic and
      neuromuscular diseases (NNMD) with and without inspiratory muscle weakness.
      SUBJECTS AND MEASUREMENTS: Both MIP and Pmosn were measured in 30 patients
      affected by various types of NNMD and in 41 control subjects. Pmosn was measured
      with a 5-cm latex balloon-catheter system, the balloon being held in the oral
      cavity with the lips closed. RESULTS: In control subjects, MIP was either similar
      (in female subjects) or higher (in male subjects) than Pmosn, the variation
      coefficients for the two tests being similar both in male subjects (19.3% vs
      19.1% for MIP and Pmosn, respectively) and in female subjects (27.5% vs 26.2%,
      respectively). There was no difference in the Pmosn/MIP ratios observed in the
      different diseases (one-way analysis of variance, F = 0.29, p = 0.91). In control
      subjects, a significant inverse relationship between Pmosn/MIP ratio and MIP (r =
      - 0.66, p < 0.00001) was found, ie, the lower the MIP, the higher the Pmosn/MIP
      ratio, suggesting an increasing difficulty in performing MIP as MIP values
      decreased. The majority of patients were between the prediction limits of the
      regression calculated for control subjects. At variance, patients with Duchenne
      dystrophy and low MIP were under the prediction limits of the regression
      calculated for control subjects, indicating a lower-than-expected PMOSN.
      CONCLUSIONS: In patients with NNMD, irrespective of the etiology, we found the
      following: (1) Pmosn does not overcome the limitations of MIP measurement; (2)
      the two maneuvers are not interchangeable, but rather complement one another in
      the assessment of inspiratory muscle strength; (3) Pmosn may underestimate muscle
      strength as assessed by MIP in patients with NNMD with inspiratory muscle
      weakness; and (4) in patients with low MIP, the lower-than-expected Pmosn/MIP
      ratio confirms inspiratory muscle weakness.

PMID- 11296178
TI  - Steady-state plasma and intrapulmonary concentrations of levofloxacin and
      ciprofloxacin in healthy adult subjects.
AB  - STUDY OBJECTIVE: To determine the steady-state plasma, epithelial lining fluid
      (ELF), and alveolar macrophage (AM) concentrations of levofloxacin and
      ciprofloxacin. DESIGN: Multiple-dose, open-label, randomized pharmacokinetic
      study. PARTICIPANTS: Thirty-six healthy, nonsmoking adult subjects were
      randomized either to oral levofloxacin, 500 or 750 mg once daily for five doses,
      or ciprofloxacin, 500 mg q12h for nine doses. INTERVENTIONS: Venipuncture,
      bronchoscopy, and BAL were performed in each subject at 4 h, 12 h, or 24 h after
      the last administered dose of antibiotic. MEASUREMENT AND RESULTS: Mean plasma
      concentrations of levofloxacin and ciprofloxacin were similar to those previously
      reported. For once-daily dosing of levofloxacin, 500 mg, the mean (+/- SD) steady
      state concentrations at 4 h, 12 h, and 24 h in ELF were 9.9 +/- 2.7 microg/mL,
      6.5 +/- 2.5 microg/mL, and 0.7 +/- 0.4 microg/mL, respectively; AM concentrations
      were 97.9 +/- 80.0 microg/mL, 36.7 +/- 23.4 microg/mL, and 13.8 +/- 16.0
      microg/mL, respectively. For levofloxacin, 750 mg, the mean steady-state
      concentrations in ELF were 22.1 +/- 14.9 microg/mL, 9.2 +/- 5.3 microg/mL, and
      1.5 +/- 0.8 microg/mL, respectively; AM concentrations were 105.1 +/- 65.5
      microg/mL, 36.2 +/- 26.1 microg/mL, and 15.1 +/- 2.0 microg/mL, respectively. The
      concentrations of ciprofloxacin at 4 h and 12 h in ELF were 1.9 +/- 0.9 microg/mL
      and 0.4 +/- 0.1 microg/mL, respectively; AM concentrations were 34.9 +/- 23.2
      microg/mL and 6.8 +/- 5.9 microg/mL, respectively. The differences in the ELF
      concentrations of the two levofloxacin groups vs those of the ciprofloxacin group
      were significant (p < 0.05) at each sampling time. CONCLUSIONS: Levofloxacin was
      more extensively distributed into intrapulmonary compartments than ciprofloxacin
      and achieved significantly higher steady-state concentrations in plasma and ELF
      during the 24 h after drug administration.

PMID- 11296179
TI  - Effect of size and disease on estimated deposition of drugs administered using
      jet nebulization in children with cystic fibrosis.
AB  - STUDY OBJECTIVES: To develop a model that quantified the nebulizer output that
      was inhaled by subjects with cystic fibrosis (CF) in order to predict the amount
      of drug likely to enter the upper airway contained in particles small enough to
      be deposited in the lower respiratory tract of individual patients. DESIGN: Forty
      three patients (age, 6 to 18 years) with CF, with FEV(1) of 26 to 124% of
      predicted, breathed through a nebulizer circuit with a pneumotachograph in place
      at the distal end. Algorithms were developed from the measured flows through the
      pneumotachograph, allowing partitioning of inspiration into undiluted aerosol and
      fresh gas. In order to validate the algorithms, argon was added to the nebulizing
      gas flow and then its concentration was analyzed at the mouth by mass
      spectrometry. RESULTS: Predictions of the concentration of argon at the mouth
      were concordant with that measured by mass spectrometry, thus validating the
      model. Combining data from the model with in vitro nebulizer performance data,
      predictions for estimates for lung deposition for individuals were possible.
      Total estimate was independent of patient size or FEV(1). The respiratory duty
      cycle was 0.44 +/- 0.05 (mean +/- SD) and correlated (r = 0.91, p < 0.001) with
      estimated deposition and minute ventilation (r = 0.60, p < 0.01). However, when
      expressed in milligrams per kilogram of body weight, the estimated deposition in
      smaller children was fourfold higher than in larger children. CONCLUSIONS: If the
      effect of patient size and pattern of breathing on estimated drug deposition are
      not considered when prescribing drugs given by nebulization, the result may be
      overdosing younger children, underdosing older children, or both.

PMID- 11296180
TI  - Plasma and BAL fluid concentrations of antimicrobial peptides in patients with
      Mycobacterium avium-intracellulare infection.
AB  - STUDY OBJECTIVES: To investigate the roles of human alpha-defensin (HAD), human
      beta-defensin (HBD)-1, and HBD-2, novel antimicrobial peptides, in patients with
      Mycobacterium avium-intracellulare infection (MAI). PATIENTS: The study included
      25 patients (10 men) with MAI who visited our hospital between June 1998 and
      August 1999. MEASUREMENTS AND RESULTS: In patients with pulmonary MAI, we
      measured HAD and HBD-1, and HBD-2 levels in plasma and in BAL fluid (BALF) by
      radioimmunoassay. Plasma concentrations of HAD and HBD-2 in those patients were
      higher than those in control subjects, whereas HBD-1 levels were similar to those
      in the control subjects. High levels of HAD and HBD-2, but not HBD-1, also were
      observed in the BALF of MAI patients. There was a positive correlation between
      HAD and interleukin (IL)-8 concentrations in the BALF of patients with MAI. BALF
      HBD-2 concentrations also correlated positively with those of plasma HBD-2 and
      BALF IL-1 beta in MAI patients. Patients with cavity formation on the chest
      roentgenogram had higher HAD and HBD-2 levels in their BALF than those of
      patients without cavity formation. Treatment with clarithromycin combined with
      two or three other antibiotics, including ethambutol, rifampicin, ofloxacin, or
      ciprofloxacin, for at least 6 months resulted in a significant fall in plasma HBD
      2 concentrations in responders, but not in nonresponders. CONCLUSION: Our
      findings suggest that HAD and HBD-2 may participate in host defense and local
      remodeling of the respiratory tract in patients with MAI and that plasma HBD-2
      levels may be a useful marker of disease activity in patients with pulmonary MAI.

PMID- 11296181
TI  - Diagnostic value of CYFRA 21-1 tumor marker and CEA in pleural effusion due to
      mesothelioma.
AB  - STUDY OBJECTIVE: The aim of our study was to assess the clinical value of CYFRA
      21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are
      complementary to cytology in the diagnosis of malignant mesotheliomas. PATIENTS:
      We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106
      patients (benign lung disease, 34 patients; bronchogenic and metastatic
      carcinoma, 40 patients; mesothelioma, 32 patients). METHODS: CEA and CYFRA 21--1
      levels were determined by means of two commercial enzyme immunoassays. RESULTS:
      The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis
      of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In
      all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%,
      respectively, with a specificity of 80% and 91%, respectively. The sensitivity of
      CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%,
      respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19
      cases of mesothelioma (89.5%) with a negative or uncertain cytology. The
      association of the tumor marker assay and the cytology allowed a correct
      diagnosis in 30 of 32 cases of mesothelioma (93.7%). CONCLUSION: This study
      suggests that CYFRA 21--1 would provide a useful parameter for the differential
      diagnosis between benign and malignant PE from mesothelioma when the result of
      cytology is negative or uncertain and the clinical context does not allow a more
      aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could
      provide details for a differential diagnosis between mesotheliomas and
      carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly
      suggestive of mesothelioma, whereas high levels of CEA alone or high levels of
      both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

PMID- 11296182
TI  - Typical and atypical pulmonary carcinoids : outcome in patients presenting with
      regional lymph node involvement.
AB  - STUDY OBJECTIVE: Typical pulmonary carcinoid tumors are well-differentiated
      neuroendocrine tumors that are associated with good patient survival rates, while
      atypical carcinoid tumors are more aggressive and have worse patient survival
      rates. Because these tumors rarely involve the thoracic lymph nodes at
      presentation, it is currently unknown to what extent the presence of thoracic
      lymph node metastases at the time of diagnosis influences patient survival.
      METHODS: A computerized search of the medical records for pulmonary carcinoid
      tumor at the Mayo Clinic from 1976 to 1997 revealed 517 patients, from which we
      identified 36 patients with pulmonary carcinoid tumors involving regional
      thoracic lymph nodes but without distant disease. For each patient, we reviewed
      the tumor histology, stage, and outcome. In addition, because the histologic
      criteria for the diagnosis of carcinoid tumors had changed significantly during
      the time of the study, we reexamined all of the histologic specimens using the
      current World Health Organization (WHO) criteria for classifying pulmonary
      neuroendocrine tumors. RESULTS: After reclassification with the WHO criteria for
      neuroendocrine tumors, 23 patients had typical carcinoid tumors with thoracic
      lymph node involvement. At the last follow-up, 19 patients had no evidence of
      disease (NED), 2 patients had developed systemic metastases (SM) and are still
      alive, and 2 patients had died. Eleven patients had atypical carcinoid tumors
      with thoracic lymph node involvement. At the last follow-up, four patients had
      NED, seven patients had developed SM within a median time of 17 months, and six
      patients with SM died shortly thereafter (median survival time, 25.5 months),
      while one is still alive. Two patients had been reclassified with large cell
      neuroendocrine carcinoma at the time of this review; both of these patients had
      developed SM (at 4 months and 21 months after diagnosis) and had died (at 15
      months and 21 months after diagnosis, respectively). CONCLUSIONS: These data
      suggest that patients with atypical pulmonary carcinoid tumors with regional
      lymph node metastases have a high likelihood of developing recurrent disease if
      treated with surgical resection alone and have significantly worse outcome (p <
      0.001) compared to those patients with typical carcinoid tumors with thoracic
      lymph node involvement.

PMID- 11296183
TI  - Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial.
AB  - STUDY OBJECTIVES: To determine whether sedation with propofol would lead to
      shorter times to tracheal extubation and ICU length of stay than sedation with
      midazolam. DESIGN: Multicenter, randomized, open label. SETTING: Four academic
      tertiary-care ICUs in Canada. PATIENTS: Critically ill patients requiring
      continuous sedation while receiving mechanical ventilation. INTERVENTIONS: Random
      allocation by predicted requirement for mechanical ventilation (short sedation
      stratum, < 24 h; medium sedation stratum, > or = 24 and < 72 h; and long sedation
      stratum, > or = 72 h) to sedation regimens utilizing propofol or midazolam.
      MEASUREMENTS AND RESULTS: Using an intention-to-treat analysis, patients
      randomized to receive propofol in the short sedation stratum (propofol, 21
      patients; midazolam, 26 patients) and the long sedation stratum (propofol, 4
      patients; midazolam, 10 patients) were extubated earlier (short sedation stratum:
      propofol, 5.6 h; midazolam, 11.9 h; long sedation stratum: propofol, 8.4 h;
      midazolam, 46.8 h; p < 0.05). Pooled results showed that patients treated with
      propofol (n = 46) were extubated earlier than those treated with midazolam (n =
      53) (6.7 vs 24.7 h, respectively; p < 0.05) following discontinuation of the
      sedation but were not discharged from ICU earlier (94.0 vs 63.7 h, respectively;
      p = 0.26). Propofol-treated patients spent a larger percentage of time at the
      target Ramsay sedation level than midazolam-treated patients (60.2% vs 44.0%,
      respectively; p < 0.05). Using a treatment-received analysis, propofol sedation
      either did not differ from midazolam sedation in time to tracheal extubation or
      ICU discharge (sedation duration, < 24 h) or was associated with earlier tracheal
      extubation but longer time to ICU discharge (sedation duration, > or = 24 h, < 72
      h, or > or = 72 h). CONCLUSIONS: The use of propofol sedation allowed for more
      rapid tracheal extubation than when midazolam sedation was employed. This did not
      result in earlier ICU discharge.

PMID- 11296184
TI  - Pneumonia in patients with severe burns : a classification according to the
      concept of the carrier state.
AB  - OBJECTIVE: To establish baseline values of pneumonia incidence and mortality and
      to distinguish primary endogenous from secondary endogenous and exogenous
      pneumonias in a homogeneous patient population with severe burns. DESIGN: Cohort
      study. SETTING: A six-bed burn ICU. PATIENTS: All patients of > or = 14 years
      admitted to the ICU between January 1995 and June 1996 with a total body surface
      area burn of > or = 20%. INTERVENTION: Collection of data on surveillance samples
      from throat and rectum on admission and twice weekly afterward, and pneumonias
      during the ICU stay. MEASUREMENTS AND RESULTS: Fifty-six patients fulfilled the
      criteria of the study. Mean age was 43 +/- 19.8 years; total body surface area
      burn, 41 +/- 18.2%; the area of full-thickness burn was 24 +/- 17.7%. Forty-one
      patients required mechanical ventilation. Twenty-seven patients (48%) experienced
      37 episodes of pneumonia. Twenty-one pneumonias were of primary endogenous
      development, ie, caused by potential pathogens carried in the admission flora.
      There were 14 secondary endogenous and 2 exogenous infections caused by
      microorganisms acquired on the burn unit. Inhalation injury was identified in 26
      patients. The pneumonia rate was two times higher in the subset of patients with
      inhalation injury compared with the group of patients without inhalation injury
      (p < 0.001). Overall mortality was 25%. CONCLUSIONS: This study shows that
      pneumonia in burn patients is mainly an endogenous problem. Interventions that
      prevent the development of endogenous infections deserve prospective evaluation
      in patients with severe burns.

PMID- 11296185
TI  - Evaluating the validity of responsiveness to inhaled nitric oxide in pediatric
      patients with ARDS: an analytic tool.
AB  - OBJECTIVES: To determine whether improved oxygenation indicates a valid response
      to inhaled nitric oxide (iNO) therapy in patients with pediatric ARDS, and to
      establish an analytic tool to differentiate the iNO effects from those of other
      interactive factors in pediatric patients with ARDS. DESIGN: Consecutive case
      series evaluated by post hoc analysis tool. PATIENTS AND METHODS: Nineteen
      patients treated with iNO for ARDS or pulmonary hypertension were enrolled in our
      study. We evaluated the PaO(2)/fraction of inspired oxygen ratio (PF ratio),
      oxygenation index (OI), patient position (prone vs supine), PaCO(2), pH, and
      vasoactive drug support, and classified patients' responsiveness to iNO into
      three categories: (1) possible response, an increase in PF ratio, with no
      alteration of the aforementioned variables in a direction known to improve
      oxygenation; (2) nonspecific response, an increase in PF ratio with no increase
      in OI, and alteration of one or more of the other four criteria in a direction
      known to improve oxygenation; and (3) undetermined response, an increase in both
      the PF ratio and OI, indicating a deliberate augmentation in ventilator support.
      RESULTS: A total of 119 data points were evaluated. Fifty data points (42%)
      exhibited no response to iNO. Thirty-two data points (27%) were classified as
      having possible responses, 35 data points (29%) as nonspecific, and 2 data points
      (2%) as undetermined responses to the iNO treatment. CONCLUSIONS: In ARDS,
      improved oxygenation amid iNO treatment is multifactorial. In only 27% of our
      evaluated data points could the increase in PF ratio be attributed to iNO. We
      suggest that when clinically utilizing iNO, the interactive factors described by
      us should be taken into account for data analysis.

PMID- 11296186
TI  - Long-term intermittent dobutamine infusion combined with oral amiodarone improves
      the survival of patients with severe congestive heart failure.
AB  - STUDY OBJECTIVE: To evaluate the effects of long-term intermittent dobutamine
      infusion (IDI) with concomitant administration of low-dose amiodarone in patients
      with congestive heart failure (CHF) refractory to standard medical treatment.
      DESIGN: Prospective, interventional clinical trial. SETTING: Inpatient and
      outpatient heart failure clinic in a university teaching hospital. PATIENTS AND
      INTERVENTIONS: Twenty-two patients with CHF refractory to standard treatment who
      could be weaned from dobutamine therapy after an initial 72-h infusion were
      included in this study. The first 11 patients (group 1) were treated with IDI, 10
      micromin, as needed (mean, once every 16 days, lasting for 12 to 48 h); the next
      11 patients (group 2) received oral amiodarone, 400 mg/d, and IDI, 10
      microg/kg/min, for 8 h every 7 days. MEASUREMENT AND RESULTS: There were no
      differences in baseline clinical, hemodynamic, and five biochemical
      characteristics between the two groups. The left ventricular ejection fraction
      was 13.5 +/- 4.5% in group 1 vs 15.5 +/- 4.9% in group 2 (mean +/- SD; p =
      0.451); mean pulmonary capillary wedge pressure was 31.3 +/- 4.4 mm Hg vs 29.4 +/
      3.3 mm Hg (p = 0.316); serum creatinine was 1.9 +/- 0.4 mg/dL vs 1.6 +/- 0.5
      mg/dL (p = 0.19); and serum Na was 139.6 +/- 6.2 mEq/L vs 138.4 +/- 3.1 mEq/L (p
      = 0.569). At 12 months of follow-up, 1 of 11 patients (9%) was alive in group 1
      vs 6 of 11 patients (55%) in group 2 (p = 0.011). Furthermore, in group 2, the
      functional status improved significantly within the first 3 months of treatment,
      from New York Heart Association functional class IV to 2.63 +/- 0.5 (p = 0.0001).
      CONCLUSION: Long-term IDI in conjunction with amiodarone, added to conventional
      drugs, improved clinical status and survival of patients with severe CHF.

PMID- 11296187
TI  - Risk factors for ARDS in the United States: analysis of the 1993 National
      Mortality Followback Study.
AB  - OBJECTIVE: To identify specific comorbid factors that are present in US decedents
      with ARDS. DESIGN: We searched the 1993 National Mortality Followback Study for
      all decedents who had a code for ARDS mentioned on their death certificate. We
      also searched for comorbid conditions both on the death certificates (sepsis,
      medical or surgical misadventures, cirrhosis) and in the study database (current
      or former smoking, use of alcohol at least 3 d/wk, race, gender, and age). We
      calculated proportional mortality ratios (PMRs) for these risk factors. RESULTS:
      Of the 19,003 decedents for whom data were available, 252 decedents, representing
      an estimated 19,460 US decedents, had ARDS listed on their death certificate.
      PMRs among decedents with ARDS were significantly increased for medical or
      surgical misadventures (PMR, 11.8; 95% confidence interval [CI], 3.8 to 36.7),
      sepsis (PMR, 5.6; 95% CI, 2.0 to 16.0), nonwhite race (PMR, 2.6; 95% CI, 1.4 to
      5.0), and cirrhosis (PMR, 2.2; 95% CI, 1.1 to 4.6). PMRs were increased but not
      statistically significant for current smokers (PMR, 1.2; 95% CI, 0.5 to 3.0) or
      former smokers (PMR, 1.8; 95% CI, 0.7 to 4.3) compared to never smokers, and
      drinking alcohol on > or = 3 d/wk in the year prior to death, when compared to
      drinking alcohol less than < 3 d/wk (PMR, 1.8; 95% CI, 0.6 to 4.9). CONCLUSIONS:
      The results of this study confirm the positive associations between ARDS
      mortality and the presence of sepsis and cirrhosis, and suggest possible new
      relationships between ARDS mortality and nonwhite individuals and patients with
      medical or surgical misadventures.

PMID- 11296188
TI  - The evidence base for management of acute exacerbations of COPD: clinical
      practice guideline, part 1.

PMID- 11296189
TI  - Management of acute exacerbations of COPD: a summary and appraisal of published
      evidence.
AB  - STUDY OBJECTIVES: To critically review the available data on the diagnostic
      evaluation, risk stratification, and therapeutic management of patients with
      acute exacerbations of COPD. DESIGN, SETTING, AND PARTICIPANTS: English-language
      articles were identified from the following databases: MEDLINE (from 1966 to week
      5, 2000), EMBASE (from 1974 to week 18, 2000), HealthStar (from 1975 to June
      2000), and the Cochrane Controlled Trials Register (2000, issue 1). The best
      available evidence on each subtopic then was selected for analysis. Randomized
      trials, sometimes buttressed by cohort studies, were used to evaluate therapeutic
      interventions. Cohort studies were used to evaluate diagnostic tests and risk
      stratification. Study design and results were summarized in evidence tables.
      Individual studies were rated as to their internal validity, external validity,
      and quality of study design. Statistical analyses of combined data were not
      performed. MEASUREMENT AND RESULTS: Limited data exist regarding the utility of
      most diagnostic tests. However, chest radiography and arterial blood gas sampling
      appear to be useful, while short-term spirometry measurements do not. In terms of
      the risk of relapse and the risk of death after hospitalization for an acute
      exacerbation, there are identifiable clinical variables that are associated with
      these outcomes. Therapies for which there is evidence of efficacy include
      bronchodilators, corticosteroids, and noninvasive positive-pressure ventilation.
      There is also support for the use of antibiotics in patients with more severe
      exacerbations. Based on limited data, mucolytics and chest physiotherapy do not
      appear to be of benefit, and oxygen supplementation appears to increase the risk
      of respiratory failure in an identifiable subgroup of patients. CONCLUSIONS:
      Although suggestions for appropriate management can be made based on available
      evidence, the supporting literature is spotty. Further high-quality research is
      needed and will require an improved, generally acceptable, and transportable
      definition of the syndrome "acute exacerbation of COPD" and improved methods for
      observing and measuring outcomes.

PMID- 11296190
TI  - Current status of the implantable cardioverter-defibrillator.
AB  - Clinical trials have established the superiority of the implantable cardioverter
      defibrillator (ICD) over antiarrhythmic drug therapy in survivors of sudden
      cardiac death and in high-risk patients with coronary artery disease. The ICD has
      evolved to overcome the limitation of earlier devices that required thoracotomy
      for implantation and were fraught with inappropriate shock delivery. Current ICDs
      are implanted in a similar manner to cardiac pacemakers and incorporate
      sophisticated rhythm-discrimination algorithms to prevent inappropriate therapy.
      Managing the patient with an ICD requires an understanding of the
      multiprogrammable features of modern devices. Drug interactions and potential
      sources of electromagnetic interference may adversely affect ICD function.
      Driving restrictions may be necessary under certain conditions. The cost
      effectiveness of ICD therapy appears favorable, given the marked survival benefit
      seen in randomized trials relative to antiarrhythmic drug treatment. The growing
      number of ICD recipients necessitates an understanding of the specialized
      features of the modern ICD and the role of device therapy in clinical practice.

PMID- 11296191
TI  - GI complications in patients receiving mechanical ventilation.
AB  - Mechanical ventilation (MV) can be lifesaving by maintaining gas exchange until
      the underlying disorders are corrected, but it is associated with numerous organ
      system complications, which can significantly affect the outcome of critically
      ill patients. Like other organ systems, GI complications may be directly
      attributable to MV, but most are a reflection of the severity of the underlying
      disease that required intensive care. The interactions of the underlying critical
      illness and MV with the GI tract are complex and can manifest in a variety of
      clinical pictures. Incorporated in this review are discussions of the most
      prevalent GI complications associated with MV, and current diagnosis and
      management of these problems.

PMID- 11296192
TI  - Protecting the myocardium from ischemic injury: a critical role for alpha(1)
      adrenoreceptors?
AB  - Ischemic preconditioning (IPC) refers to the ability of short periods of ischemia
      to make the myocardium more resistant to a subsequent ischemic insult. It is the
      most powerful form of endogenous protection against myocardial infarction and has
      been demonstrated in all species evaluated to date. However, the cellular
      mechanisms that drive IPC remain poorly understood. This hypothesis describes an
      important role for alpha(1)-adrenoreceptors in mediating IPC and discusses the
      underlying mechanisms by which this is likely achieved. alpha(1)-Adrenoreceptors
      are present in the myocardium of all mammalian species, and several lines of
      evidence suggest that they play an important role in mediating IPC. During
      periods of myocardial hypoxia/ischemia, cardiomyocytes have to rely solely on
      anaerobic glycolysis for energy production; for this, the cells have to depend on
      increased glucose entry inside the cell as well as increased glycolysis.
      Stimulation of alpha(1)-adrenoreceptors increases glucose transport inside the
      cardiomyocytes by translocating glucose transporter (GLUT)-1 and GLUT-4 from the
      cytoplasm to the plasma membrane, enhances glycogenolysis by activating
      phosphorylase kinase, increases the rate of glycolysis by activating the enzyme
      phosphofructokinase, reduces intracellular acidity produced during excessive
      glycolysis by activating the Na(+)/H(+) exchanger, and inhibits apoptosis by
      increasing the levels of the antiapoptotic protein Bcl-2. Myocardial ischemia
      produces an increase in the expression of alpha(1)-adrenoreceptors in
      cardiomyocytes, as well as increases the levels of its agonist norepinephrine by
      several fold. During ischemic states, upregulation of alpha(1)-adrenoreceptors
      and increase in norepinephrine release could be a powerful adaptive mechanism
      that drives IPC. An understanding into the role of alpha(1)-adrenoreceptors in
      mediating IPC could not only point to newer treatments for limiting myocardial
      damage during myocardial infarction or heart surgery, but could also help in
      avoiding the use of alpha(1)-antagonists in patients with ischemic heart disease.

PMID- 11296193
TI  - A solitary pulmonary nodule with zoonotic implications.

PMID- 11296194
TI  - Differing chest imaging patterns in three patients are caused by one microbe.

PMID- 11296195
TI  - Time for introspection.

PMID- 11296196
TI  - Considerations in the relationship between the American College of Chest
      Physicians and industry.

PMID- 11296197
TI  - Short-term effects of wood smoke exposure on the respiratory system among
      charcoal production workers.
AB  - STUDY OBJECTIVES: We aimed to investigate the short-term respiratory effects of
      heavy, occupational wood smoke exposure among traditional charcoal production
      workers. PATIENTS AND SETTING: A total of 22 charcoal workers (mean age, 41
      years; 9 current smokers, 5 ex-smokers, and 8 nonsmokers) were studied and
      compared with a control group of 35 farmers residing in Perama, Rethymnon, Crete.
      RESULTS: The charcoal workers were exposed to wood smoke for an average of 14 h/d
      during a mean of 23.7 days required for the burning of kilns. The workers under
      study were found to have significantly more cough (odds ratio [OR], 4.8; 95%
      confidence interval [CI], 1.2 to 19.7), sputum production (OR, 6; 95% CI, 1.4 to
      26.5), wheezing (OR, 7.7; 95% CI, 1.4 to 41.5), dyspnea (OR, 28.7; 95% CI, 5.4 to
      153), and hemoptysis (OR, 2.7; 95% CI, 0.7 to 55) than the control group. The
      prevalence of respiratory symptoms such as cough, sputum production, wheezing,
      and dyspnea in the charcoal workers was significantly elevated during the
      exposure period (OR, 5.4; 95% CI, 1.1 to 17.7; OR, 5.7; 95% CI, 1 to 31; OR, 9.8;
      95% CI, 1 to 88; and OR, 36.7; 95% CI, 1 to 327, respectively). The mean +/- SD
      percent of predicted values of FVC, FEV(1), FEV(1)/FVC ratio, and forced
      expiratory flow at 25 to 75% of FVC during the exposure period were significantly
      lower than those before exposure: 106 +/- 10.8 vs 101 +/- 11.9, p < 0.01; 104 +/-
      16 vs 97 +/- 15, p < 0.001; 81 +/- 9 vs 78 +/- 8, p < 0.001; and 95 +/- 27 vs 80
      +/- 25, p < 0.01, respectively. The mean +/- SD value of peak expiratory flow at
      midday and in the evening during the exposure were significantly lower than
      before: 524 +/- 131 L/min vs 548 +/- 108 L/min, p = 0.03; and 521 +/- 135 L/min
      vs 547 +/- 131 L/min, p = 0.02, respectively. CONCLUSIONS: Our results suggest
      that wood smoke exposure in charcoal workers is associated with increased
      respiratory symptoms and decreased pulmonary function. Longitudinal studies are
      needed to determine potential long-term adverse respiratory effects.

PMID- 11296198
TI  - Pleurisy, fever, and rapidly progressive pleural effusion in a healthy, 29-year
      old physician.

PMID- 11296199
TI  - Functional significance of the decreased attenuation sign on expiratory CT in
      pulmonary sarcoidosis : report of four cases.
AB  - We describe four patients with proven sarcoidosis and minor pulmonary involvement
      according to high-resolution CT (HRCT) findings in whom the recently described
      sign of decreased attenuation on expiratory HRCT scan appeared associated with
      the reduction of the single-breath diffusing capacity of the lung for carbon
      monoxide (DLCO) and the DLCO adjusted for alveolar volume. These alterations
      were, in part, reversible under steroid treatment. Major indexes of airway
      obstruction (FEV(1)/vital capacity ratio and FEV(1)) were normal, while the
      maximum expiratory flow at 25% above the residual volume of FVC was reduced.
      These observations suggest that an expiratory HRCT mosaic pattern and diffusion
      impairment may be early findings in pulmonary sarcoidosis and may be useful for
      its detection and follow-up.

PMID- 11296200
TI  - Bilateral phrenic paralysis in a patient with systemic lupus erythematosus.
AB  - Respiratory manifestations of systemic lupus erythematosus (SLE) are frequent.
      They include respiratory muscle abnormalities, which have been implicated in the
      pathogenesis of the "shrinking lung syndrome" (SLS). We report the case of a
      patient with this syndrome, in whom diaphragmatic paralysis due to demyelinating
      phrenic lesions was diagnosed at the same time as SLE. Follow-up studies showed a
      favorable clinical and diaphragmatic outcome with corticosteroid therapy, but
      little change in spirometry. It is concluded that severe diaphragm palsy is
      possibly due to phrenic nerve lesions in SLE, and that the link between diaphragm
      dysfunction and the SLS is probably not a straightforward one.

PMID- 11296201
TI  - Influenza pneumonia in lung transplant recipients: clinical features and
      association with bronchiolitis obliterans syndrome.
AB  - Influenza infection is increasingly recognized to cause significant morbidity and
      mortality in the community, especially in pediatric patients and elderly persons.
      Influenza infection, however, has not been well described among thoracic organ
      transplant recipients. We provide the first detailed clinical, radiographic, and
      histologic description of influenza pneumonia among three lung transplant
      recipients. The presentation varied considerably among the three patients and, in
      some cases, was atypical for influenza. Despite treatment, a persistent decline
      in pulmonary function occurred in all three patients after the acute illness.
      Interestingly, on follow-up biopsy specimens, each patient had histologic
      evidence of acute rejection and/or obliterative bronchiolitis. Additional
      research, therefore, is needed to clarify the relationship between influenza
      infection, acute rejection, and obliterative bronchiolitis.

PMID- 11296202
TI  - Continuous calcium chloride infusion for massive nifedipine overdose.
AB  - A 37-year-old woman presented with persistent hypotension and noncardiogenic
      pulmonary edema after massive nifedipine overdose. Judicious use of continuous
      and prolonged high-dose IV calcium infusion was administered to provide sustained
      increases in serum ionic calcium level (approximately 2 mmol/L) and was able to
      improve the hemodynamic status without any major adverse reaction.

PMID- 11296203
TI  - Complications of percutaneous tracheostomy.
AB  - Percutaneous tracheostomy is a technique that, reputedly, is simple to perform
      and causes few complications. It is routinely used in intensive care. We present
      two patients with tracheal stenosis. In one patient, we had to perform an
      anastomotic resection to cure the patient; in the other patient, we had to place
      an endoluminal conformer. To our knowledge, this complication has not been
      reported in association with the use of this technique.

PMID- 11296204
TI  - Minocycline-induced pancreatitis in cystic fibrosis.
AB  - We report two cases of acute pancreatitis secondary to minocycline use in adults
      with cystic fibrosis (CF). This minocycline complication has not previously been
      reported. Given the increased use of minocycline in the adult CF population to
      treat resistant bacteria, awareness of this potential adverse effect is
      imperative. As both of these individuals with CF had class IV genotypes and
      pancreatic sufficiency, close observation is warranted in the future to determine
      if persons with pancreatic-sufficient CF are at an increased risk for minocycline
      induced pancreatitis.

PMID- 11296205
TI  - Hemoptysis due to migration of a fractured Kirschner wire.
AB  - We report a rare complication related to the insertion of Kirschner wires for
      stabilization of an acromioclavicular separation. Five years after placement of
      the Kirschner wires, the patient presented with hemoptysis. On review of chest
      radiographs, a fractured wire was found to have migrated from the
      acromioclavicular joint, through the hemithorax and into the trachea.

PMID- 11296206
TI  - Definitions in sleep-disordered breathing.

PMID- 11296207
TI  - Why blame private practitioners?

PMID- 11296208
TI  - Chest radiography following thoracentesis.

PMID- 11296209
TI  - Coronary vasospasm in hypertrophic cardiomyopathy.

PMID- 11296210
TI  - Deception in bronchodilator inhaler use.

PMID- 11296211
TI  - Pneumothorax: is chest tube clamp necessary before removal?

PMID- 11296212
TI  - CT scanning and bilateral surgery for unilateral primary pneumothorax?

PMID- 11296213
TI  - The role of nuclear factor-kappa B activation in airway inflammation following
      adenovirus infection and COPD.

PMID- 11296214
TI  - Etiology of community-acquired pneumonia requiring hospitalization in Japan.

PMID- 11296215
TI  - Chicken soup or Jewish medicine.

PMID- 11296216
TI  - Structural and functional studies of MinD ATPase: implications for the molecular
      recognition of the bacterial cell division apparatus.
AB  - Proper placement of the bacterial cell division site requires the site-specific
      inactivation of other potential division sites. In Escherichia coli, selection of
      the correct mid-cell site is mediated by the MinC, MinD and MinE proteins. To
      clarify the functional role of the bacterial cell division inhibitor MinD, which
      is a membrane-associated ATPase that works as an activator of MinC, we determined
      the crystal structure of a Pyrococcus furiosus MinD homologue complexed with a
      substrate analogue, AMPPCP, and with the product ADP at resolutions of 2.7 and
      2.0 A, respectively. The structure reveals general similarities to the
      nitrogenase iron protein, the H-Ras p21 and the RecA-like ATPase domain. Alanine
      scanning mutational analyses of E.coli MinD were also performed in vivo. The
      results suggest that the residues around the ATP-binding site are required for
      the direct interaction with MinC, and that ATP binding and hydrolysis play a role
      as a molecular switch to control the mechanisms of MinCDE-dependent bacterial
      cell division.

PMID- 11296217
TI  - Crystal structures of complexes of the small ribosomal subunit with tetracycline,
      edeine and IF3.
AB  - The small ribosomal subunit is responsible for the decoding of genetic
      information and plays a key role in the initiation of protein synthesis. We
      analyzed by X-ray crystallography the structures of three different complexes of
      the small ribosomal subunit of Thermus thermophilus with the A-site inhibitor
      tetracycline, the universal initiation inhibitor edeine and the C-terminal domain
      of the translation initiation factor IF3. The crystal structure analysis of the
      complex with tetracycline revealed the functionally important site responsible
      for the blockage of the A-site. Five additional tetracycline sites resolve most
      of the controversial biochemical data on the location of tetracycline. The
      interaction of edeine with the small subunit indicates its role in inhibiting
      initiation and shows its involvement with P-site tRNA. The location of the C
      terminal domain of IF3, at the solvent side of the platform, sheds light on the
      formation of the initiation complex, and implies that the anti-association
      activity of IF3 is due to its influence on the conformational dynamics of the
      small ribosomal subunit.

PMID- 11296218
TI  - Expression of microbial virulence proteins in Saccharomyces cerevisiae models
      mammalian infection.
AB  - Bacterial virulence proteins that are translocated into eukaryotic cells were
      expressed in Saccharomyces cerevisiae to model human infection. The subcellular
      localization patterns of these proteins in yeast paralleled those previously
      observed during mammalian infection, including localization to the nucleus and
      plasma membrane. Localization of Salmonella SspA in yeast provided the first
      evidence that SspA interacts with actin in living cells. In many cases,
      expression of the bacterial virulence proteins conferred genetically exploitable
      growth phenotypes. In this way, Yersinia YopE toxicity was demonstrated to be
      linked to its Rho GTPase activating protein activity. YopE blocked polarization
      of the yeast cytoskeleton and cell cycle progression, while SspA altered polarity
      and inhibited depolymerization of the actin cytoskeleton. These activities are
      consistent with previously proposed or demonstrated effects on higher eukaryotes
      and provide new insights into the roles of these proteins in pathogenesis: SspA
      in directing formation of membrane ruffles and YopE in arresting cell division.
      Thus, study of bacterial virulence proteins in yeast is a powerful system to
      determine functions of these proteins, probe eukaryotic cellular processes and
      model mammalian infection.

PMID- 11296219
TI  - Type III secretion chaperone-dependent regulation: activation of virulence genes
      by SicA and InvF in Salmonella typhimurium.
AB  - Invasion of the intestinal epithelium by Salmonella sp. requires a type III
      secretion system (TTSS) common in many bacterial pathogens. TTSS translocate
      effector proteins from bacteria into eukaryotic cells. These effectors manipulate
      cellular functions in order to benefit the pathogen. In the human and animal
      pathogen Salmonella typhimurium, the expression of genes encoding the secreted
      effector molecules Sip/Ssp ABCD, SigD, SptP and SopE requires both the AraC/XylS
      like regulator InvF and the secretion chaperone SICA: In this work, an InvF
      binding site was identified in the promoter regions of three operons. SicA does
      not appear to affect InvF stability nor to bind DNA directly. However, SicA could
      be co-purified with InvF, suggesting that InvF and SicA interact with each other
      to activate transcription from the effector gene promoters. This is the first
      demonstration of a contact between a protein cofactor and an AraC/XylS family
      transcriptional regulator and, moreover, is the first direct evidence of an
      interaction between a transcriptional regulator and a TTSS chaperone. The
      regulation of effector genes described here for InvF and SicA may represent a new
      paradigm for regulation of virulence in a wide variety of pathogens.

PMID- 11296220
TI  - Perinuclear, perigranular and sub-plasmalemmal mitochondria have distinct
      functions in the regulation of cellular calcium transport.
AB  - We have identified three distinct groups of mitochondria in normal living
      pancreatic acinar cells, located (i) in the peripheral basolateral region close
      to the plasma membrane, (ii) around the nucleus and (iii) in the periphery of the
      granular region separating the granules from the basolateral area. Three
      dimensional reconstruction of confocal slices showed that the perigranular
      mitochondria form a barrier surrounding the whole of the granular region.
      Cytosolic Ca(2+) oscillations initiated in the granular area triggered
      mitochondrial Ca(2+) uptake mainly in the perigranular area. The most intensive
      uptake occurred in the mitochondria close to the apical plasma membrane. Store
      operated Ca(2+) influx through the basolateral membrane caused preferential
      Ca(2+) uptake into sub-plasmalemmal mitochondria. The perinuclear mitochondria
      were activated specifically by local uncaging of Ca(2+) in the nucleus. These
      mitochondria could isolate nuclear and cytosolic Ca(2+) signalling.
      Photobleaching experiments indicated that different groups of mitochondria were
      not luminally connected. The three mitochondrial groups are activated
      independently by specific spatiotemporal patterns of cytosolic Ca(2+) signals and
      can therefore participate in the local regulation of Ca(2+) homeostasis and
      energy supply.

PMID- 11296221
TI  - The Arabidopsis thaliana ABC transporter AtMRP5 controls root development and
      stomata movement.
AB  - In the present study, we investigated a new member of the ABC transporter
      superfamily of Arabidopsis thaliana, AtMRP5. AtMRP5 encodes a 167 kDa protein and
      exhibits low glutathione conjugate and glucuronide conjugate transport activity.
      Promotor- beta-glucuronidase fusion constructs showed that AtMRP5 is expressed
      mainly in the vascular bundle and in the epidermis, especially guard cells. Using
      reverse genetics, we identified a plant with a T-DNA insertion in AtMRP5 (mrp5
      1). mrp5-1 exhibited decreased root growth and increased lateral root formation.
      Auxin levels in the roots of mrp5-1 plants were increased. This observation may
      indicate that AtMRP5 works as an auxin conjugate transporter or that mutant
      plants are affected in ion uptake, which may lead to changes in auxin
      concentrations. Experiments on epidermal strips showed that in contrast to wild
      type, the sulfonylurea glibenclamide had no effect on stomatal opening in mrp5-1
      plants. This result strongly suggests that AtMRP5 may also function as an ion
      channel regulator.

PMID- 11296222
TI  - Structural and functional differences between two homologous mechanosensitive
      channels of Methanococcus jannaschii.
AB  - We report the molecular cloning and characterization of MscMJLR, a second type of
      mechanosensitive (MS) channel found in the archaeon Methanococcus jannaschii.
      MscMJLR is structurally very similar to MscMJ, the MS channel of M.jannaschii
      that was identified and cloned first by using the TM1 domain of Escherichia coli
      MscL as a genetic probe. Although it shares 44% amino acid sequence identity and
      similar cation selectivity with MscMJ, MscMJLR exhibits other major functional
      differences. The conductance of MscMJLR of approximately 2 nS is approximately 7
      fold larger than the conductance of MscMJ and rectifies with voltage. The channel
      requires approximately 18 kT for activation, which is three times the amount of
      energy required to activate MscMJ, but is comparable to the activation energy of
      Eco-MSCL: Our study indicates that a multiplicity of conductance-wise and
      energetically well-tuned MS channels in microbial cell membranes may provide for
      cell survival by the sequential opening of the channels upon challenge with
      different osmotic cues.

PMID- 11296223
TI  - The Wilms tumor suppressor WT1 directs stage-specific quiescence and
      differentiation of human hematopoietic progenitor cells.
AB  - WT1, a transcription factor implicated in both normal kidney differentiation and
      tumorigenesis, is also expressed in differentiating hematopoietic progenitors.
      Most human acute leukemias contain high levels of the wild-type transcript, while
      a minority have point mutations, raising the possibility that this tumor
      suppressor might have a paradoxical oncogenic effect in some hematopoietic cells.
      Using high titer retroviral infection, we demonstrate that WT1 triggers rapid
      growth arrest and lineage-specific differentiation in primary hematopoietic
      progenitors and differentiation-competent leukemia cell lines, while it induces
      cellular quiescence in a primitive subset of primary precursors. Growth arrest by
      WT1 is associated with induction of p21(CIP1), but expression of this cyclin
      dependent kinase inhibitor alone is insufficient for either cellular
      differentiation or primitive cell preservation. The effects of WT1 are enhanced
      by co-expression of its naturally occurring isoforms, and are correlated with the
      physiological expression pattern of WT1 in vivo. Our observations suggest a role
      for WT1 in the differentiation of human hematopoietic cells, and provide a
      functional model that supports its capacity as a tumor suppressor in human acute
      leukemia.

PMID- 11296224
TI  - Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor
      progression and cell invasion.
AB  - Recently we showed that partial depletion of mitochondrial DNA (genetic stress)
      or treatment with mitochondrial-specific inhibitors (metabolic stress) induced a
      stress signaling that was associated with increased cytoplasmic-free Ca(2+)
      [Ca(2+)](c). In the present study we show that the mitochondria-to-nucleus stress
      signaling induces invasive phenotypes in otherwise non-invasive C2C12 myoblasts
      and human pulmonary carcinoma A549 cells. Tumor-specific markers cathepsin L and
      transforming growth factor beta (TGFbeta) are overexpressed in cells subjected to
      mitochondrial genetic as well as metabolic stress. C2C12 myoblasts subjected to
      stress showed 4- to 6-fold higher invasion through reconstituted Matrigel
      membrane as well as rat tracheal xenotransplants in Scid mice. Activation of
      Ca(2+)-dependent protein kinase C (PKC) under both genetic and metabolic stress
      conditions was associated with increased cathepsin L gene expression, which
      contributes to increased invasive property of cells. Reverted cells with
      approximately 70% of control cell mtDNA exhibited marker mRNA contents, cell
      morphology and invasive property closer to control cells. These results provide
      insights into a new pathway by which mitochondrial DNA and membrane damage can
      contribute to tumor progression and metastasis.

PMID- 11296225
TI  - mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module.
AB  - Spatiotemporal regulation of protein kinase A (PKA) activity involves the
      manipulation of compartmentalized cAMP pools. Now we demonstrate that the muscle
      selective A-kinase anchoring protein, mAKAP, maintains a cAMP signaling module,
      including PKA and the rolipram-inhibited cAMP-specific phosphodiesterase (PDE4D3)
      in heart tissues. Functional analyses indicate that tonic PDE4D3 activity reduces
      the activity of the anchored PKA holoenzyme, whereas kinase activation stimulates
      mAKAP-associated phosphodiesterase activity. Disruption of PKA- mAKAP interaction
      prevents this enhancement of PDE4D3 activity, suggesting that the proximity of
      both enzymes in the mAKAP signaling complex forms a negative feedback loop to
      restore basal cAMP levels.

PMID- 11296226
TI  - p53 induction of heparin-binding EGF-like growth factor counteracts p53 growth
      suppression through activation of MAPK and PI3K/Akt signaling cascades.
AB  - Tumor suppressor p53 induction in response to cellular stresses activates the
      mitogen-activated protein kinase (MAPK) cascade through pathways involving Ras
      and RAF: p53's ability to activate this pathway is dependent on p53-mediated
      transcription. In order to investigate potential p53 target gene(s) involved, we
      utilized expression array analysis and identified heparin-binding epidermal
      growth factor-like growth factor (HB-EGF) as being markedly up-regulated by p53.
      In response to DNA damage, HB-EGF was induced in wild-type, but not in mutant p53
      containing cells, implying its p53 dependence. HB-EGF neutralizing antibody and
      inhibitors of EGF receptor signaling abrogated p53-induced MAPK activation.
      Expression of HB-EGF was shown to protect cells from H(2)O(2)-induced apoptosis
      through MAPK activation. Additionally, the PI3K/Akt pathway was activated in
      response to p53 signaling through HB-EGF induction, and inhibition of MAPK and
      Akt activation after DNA damage decreased cell survival in wild-type p53
      containing cells. All these findings point to a novel aspect of p53 function.
      Namely, p53-induced growth factors such as HB-EGF, which activate MAPK and Akt
      signaling, may be involved in a compensatory mechanism to alleviate adverse
      effects of cellular stresses.

PMID- 11296228
TI  - Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene.
AB  - The Raf kinases play a key role in relaying signals elicited by mitogens or
      oncogenes. Here, we report that c-raf-1(-/-) embryos are growth retarded and die
      at midgestation with anomalies in the placenta and in the fetal liver. Although
      hepatoblast proliferation does not appear to be impaired, c-raf-1(-/-) fetal
      livers are hypocellular and contain numerous apoptotic cells. Similarly, the poor
      proliferation of Raf-1(-/-) fibroblasts and hematopoietic cells cultivated in
      vitro is due to an increase in the apoptotic index of these cultures rather than
      to a cell cycle defect. Furthermore, Raf-1- deficient fibroblasts are more
      sensitive than wild- type cells to specific apoptotic stimuli, such as
      actinomycin D or Fas activation, but not to tumor necrosis factor-alpha. MEK/ERK
      activation is normal in Raf-1-deficient cells and embryos, and is probably
      mediated by B-RAF. These results indicate that the essential function of Raf-1 is
      to counteract apoptosis rather than to promote proliferation, and that effectors
      distinct from the MEK/ERK cascade must mediate the anti-apoptotic function of Raf
      1.

PMID- 11296227
TI  - MEK kinase activity is not necessary for Raf-1 function.
AB  - Raf-1 protein kinase has been identified as an integral component of the
      Ras/Raf/MEK/ERK signalling pathway in mammals. Activation of Raf-1 is achieved by
      RAS:GTP binding and other events at the plasma membrane including tyrosine
      phosphorylation at residues 340/341. We have used gene targeting to generate a
      'knockout' of the raf-1 gene in mice as well as a rafFF mutant version of
      endogenous Raf-1 with Y340FY341F mutations. Raf-1(-/-) mice die in embryogenesis
      and show vascular defects in the yolk sac and placenta as well as increased
      apoptosis of embryonic tissues. Cell proliferation is not affected. Raf-1 from
      cells derived from raf-1(FF/FF) mice has no detectable activity towards MEK in
      vitro, and yet raf-1(FF/FF) mice survive to adulthood, are fertile and have an
      apparently normal phenotype. In cells derived from both the raf-1(-/-) and raf
      1(FF/FF) mice, ERK activation is normal. These results strongly argue that MEK
      kinase activity of Raf-1 is not essential for normal mouse development and that
      Raf-1 plays a key role in preventing apoptosis.

PMID- 11296229
TI  - Loss of the maintenance methyltransferase, xDnmt1, induces apoptosis in Xenopus
      embryos.
AB  - DNA methylation is necessary for normal embryogenesis in animals. Here we show
      that loss of the maintenance methyltransferase, xDnmt1p, triggers an apoptotic
      response during Xenopus development, which accounts for the loss of specific cell
      populations in hypomethylated embryos. Hypomethylation-induced apoptosis is
      accompanied by a stabilization in xp53 protein levels after the mid-blastula
      transition. Ectopic expression of HPV-E6, which promotes xp53 degradation,
      prevents cell death, implying that the apoptotic signal is mediated by xp53. In
      addition, inhibition of caspase activation by overexpression of Bcl-2 results in
      the development of cellular masses that resemble embryonic blastomas. Embryonic
      tissue explant experiments suggest that hypomethylation alters the developmental
      potential of early embryo cells and that apoptosis is triggered by
      differentiation. Our results imply that loss of DNA methylation in differentiated
      somatic cells provides a signal via p53 that activates cell death pathways.

PMID- 11296230
TI  - Glucocorticoid-induced DNA demethylation and gene memory during development.
AB  - Glucocorticoid hormones were found to regulate DNA demethylation within a key
      enhancer of the rat liver-specific tyrosine aminotransferase (Tat) gene. Genomic
      footprinting analysis shows that the glucocorticoid receptor uses local DNA
      demethylation as one of several steps to recruit transcription factors in
      hepatoma cells. Demethylation occurs within 2-3 days following rapid (< 1 h)
      chromatin remodeling and recruitment of a first transcription factor, HNF-3. Upon
      demethylation, two additional transcription factors are recruited when chromatin
      is remodeled. In contrast to chromatin remodeling, the demethylation is stable
      following hormone withdrawal. As a stronger subsequent glucocorticoid response is
      observed, demethylation appears to provide memory of the first stimulation.
      During development, this demethylation occurs before birth, at a stage where the
      Tat gene is not yet inducible, and it could thus prepare the enhancer for
      subsequent stimulation by hypoglycemia at birth. In vitro cultures of fetal
      hepatocytes recapitulate the regulation analyzed in hepatoma cells. There fore,
      demethylation appears to contribute to the fine-tuning of the enhancer and to the
      memorization of a regulatory event during development.

PMID- 11296231
TI  - Transcription factor-dependent regulation of CBP and P/CAF histone
      acetyltransferase activity.
AB  - CREB-binding protein (CBP) and CBP-associated factor (P/CAF) are coactivators
      possessing an intrinsic histone acetyltransferase (HAT) activity. They are
      positioned at promoter regions via association with sequence-specific DNA-binding
      factors and stimulate transcription in a gene-specific manner. The current view
      suggests that coactivator function depends mainly on the strength and specificity
      of transcription factor-coactivator interactions. Here we show that two dominant
      negative mutants of hepatocyte nuclear factor-1alpha (HNF-1alpha), P447L and
      P519L, occurring in maturity onset diabetes of the young (MODY3) patients,
      exhibit paradoxically stronger interactions than the wild-type protein with
      either CBP or P/CAF. However, CBP and P/CAF recruited by these mutants lack HAT
      activity. In contrast, wild-type HNF-1alpha and other transcription factors, such
      as Sp1 or HNF-4, stimulated the HAT activity of CBP. The results suggest a more
      dynamic role for DNA-binding proteins in the transcription process than was
      considered previously. They are not only required for the recruitment of
      coactivators to the promoter but they may also modulate their enzymatic activity.

PMID- 11296232
TI  - Saccharomyces cerevisiae Elongator mutations confer resistance to the
      Kluyveromyces lactis zymocin.
AB  - Kluyveromyces lactis killer strains secrete a zymocin complex that inhibits
      proliferation of sensitive yeast genera including Saccharomyces cerevisiae. In
      search of the putative toxin target (TOT), we used mTn3:: tagging to isolate
      zymocin-resistant tot mutants from budding yeast. Of these we identified the
      TOT1, TOT2 and TOT3 genes (isoallelic with ELP1, ELP2 and ELP3, respectively)
      coding for the histone acetyltransferase (HAT)-associated Elongator complex of
      RNA polymerase II holoenzyme. Other than the typical elp ts-phenotype, tot
      phenocopies hypersensitivity towards caffeine and Calcofluor White as well as
      slow growth and a G(1) cell cycle delay. In addition, TOT4 and TOT5 (isoallelic
      with KTI12 and IKI1, respectively) code for components that associate with
      ELONGATOR: Intriguingly, strains lacking non-Elongator HATs (gcn5, hat1, hpa3 and
      sas3) or non-Elongator transcription elongation factors TFIIS (dst1) and Spt4p
      (spt4) cannot confer resistance towards the K.lactis zymocin, thus providing
      evidence that Elongator equals TOT and that Elongator plays an important role in
      signalling toxicity of the K.lactis zymocin.

PMID- 11296233
TI  - ATP-dependent chromatin remodeling facilitates nucleotide excision repair of UV
      induced DNA lesions in synthetic dinucleosomes.
AB  - To investigate the relationship between chromatin dynamics and nucleotide
      excision repair (NER), we have examined the effect of chromatin structure on the
      formation of two major classes of UV-induced DNA lesions in reconstituted
      dinucleosomes. Furthermore, we have developed a model chromatin-NER system
      consisting of purified human NER factors and dinucleosome substrates that contain
      pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) either at the center of the
      nucleosome or in the linker DNA. We have found that the two classes of UV-induced
      DNA lesions are formed efficiently at every location on dinucleosomes in a manner
      similar to that of naked DNA, even in the presence of histone H1. On the other
      hand, excision of 6-4PPs is strongly inhibited by dinucleosome assembly, even
      within the linker DNA region. These results provide direct evidence that the
      human NER machinery requires a space greater than the size of the linker DNA to
      excise UV lesions efficiently. Interestingly, NER dual incision in dinucleosomes
      is facilitated by recombinant ACF, an ATP-dependent chromatin remodeling factor.
      Our results indicate that there is a functional connection between chromatin
      remodeling and the initiation step of NER.

PMID- 11296234
TI  - Dimerization of the largest subunit of chromatin assembly factor 1: importance in
      vitro and during Xenopus early development.
AB  - To date, the in vivo importance of chromatin assembly factors during development
      in vertebrates is unknown. Chromatin assembly factor 1 (CAF-1) represents the
      best biochemically characterized factor promoting chromatin assembly during DNA
      replication or repair in human cell-free systems. Here, we identify a Xenopus
      homologue of the largest subunit of CAF-1 (p150). Novel dimerization properties
      are found conserved in both Xenopus and human p150. A region of 36 amino acids
      required for p150 dimerization was identified. Deletion of this domain abolishes
      the ability of p150 to promote chromatin assembly in vitro. A dominant-negative
      interference based on these dimerization properties occurs both in vitro and in
      vivo. In the embryo, nuclear organization was severely affected and cell cycle
      progression was impaired during the rapid early cleaving stages of Xenopus
      development. We propose that the rapid proliferation at early developmental
      stages necessitates the unique properties of an assembly factor that can ensure a
      tight coupling between DNA replication or repair and chromatin assembly.

PMID- 11296235
TI  - MOT1-catalyzed TBP-DNA disruption: uncoupling DNA conformational change and role
      of upstream DNA.
AB  - SNF2/SWI2-related ATPases employ ATP hydrolysis to disrupt protein-DNA
      interactions, but how ATP hydrolysis is coupled to disruption is not understood.
      Here we examine the mechanism of action of MOT1, a yeast SNF2/SWI2-related ATPase
      that uses ATP hydrolysis to remove TATA binding protein (TBP) from DNA. MOT1
      function requires a 17 bp DNA 'handle' upstream of the TATA box, which must be
      double stranded. Remarkably, MOT1-catalyzed disruption of TBP-DNA does not appear
      to require DNA strand separation, DNA bending or twisting of the DNA helix. Thus,
      TBP-DNA disruption is accomplished in a reaction apparently not driven by a
      change in DNA structure. MOT1 action is supported by DNA templates in which the
      handle is connected to the TATA box via single-stranded DNA, indicating that the
      upstream duplex DNA can be conformationally uncoupled from the TATA box.
      Combining these results with proposed similarities between SNF2/SWI2 ATPases and
      helicases, we suggest that MOT1 uses ATP hydrolysis to translocate along the
      handle and thereby disrupt interactions between TBP and DNA.

PMID- 11296236
TI  - The structural basis of acyl coenzyme A-dependent regulation of the transcription
      factor FadR.
AB  - FadR is an acyl-CoA-responsive transcription factor, regulating fatty acid
      biosynthetic and degradation genes in Escherichia coli. The apo-protein binds DNA
      as a homodimer, an interaction that is disrupted by binding of acyl-COA: The
      recently described structure of apo-FadR shows a DNA binding domain coupled to an
      acyl-CoA binding domain with a novel fold, but does not explain how binding of
      the acyl-CoA effector molecule > 30 A away from the DNA binding site affects
      transcriptional regulation. Here, we describe the structures of the FadR-operator
      and FadR- myristoyl-CoA binary complexes. The FadR-DNA complex reveals a novel
      winged helix-turn-helix protein-DNA interaction, involving sequence-specific
      contacts from the wing to the minor groove. Binding of acyl-CoA results in
      dramatic conformational changes throughout the protein, with backbone shifts up
      to 4.5 A. The net effect is a rearrangement of the DNA binding domains in the
      dimer, resulting in a change of 7.2 A in separation of the DNA recognition
      helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA
      responsive regulation.

PMID- 11296237
TI  - Visualizing the solvent-inaccessible core of a group II intron ribozyme.
AB  - Group II introns are well recognized for their remarkable catalytic capabilities,
      but little is known about their three-dimensional structures. In order to obtain
      a global view of an active enzyme, hydroxyl radical cleavage was used to define
      the solvent accessibility along the backbone of a ribozyme derived from group II
      intron ai5gamma. These studies show that a highly homogeneous ribozyme population
      folds into a catalytically compact structure with an extensively internalized
      catalytic core. In parallel, a model of the intron core was built based on known
      tertiary contacts. Although constructed independently of the footprinting data,
      the model implicates the same elements for involvement in the catalytic core of
      the intron.

PMID- 11296238
TI  - The Y14 protein communicates to the cytoplasm the position of exon-exon
      junctions.
AB  - We recently described an RNA-binding protein, Y14, that binds preferentially to
      spliced mRNAs and persists in the cytoplasm. Y14 is part of a multi-protein
      complex that also contains the mRNA export factor TAP. This suggests that
      splicing imprints the mRNA with a unique set of proteins that communicate the
      history of the transcript to the cytoplasm. Here, using microinjection of pre
      mRNAs into Xenopus oocyte nuclei followed by immunoprecipitation of RNase
      fragmented mRNAs from the cytoplasm, we show that Y14 is stably bound to
      sequences immediately upstream of exon-exon junctions. This feature appears to be
      unique to Y14. Using monoclonal antibodies that we produced against Aly/REF,
      another component recently reported to be an mRNA export factor, we show that
      Aly/REF is associated with spliced mRNAs in the nucleus but is not detectable on
      mRNAs in the cytoplasm. Thus, we propose that the splicing- dependent binding of
      Y14 provides a position-specific molecular memory that communicates to the
      cytoplasm the location of exon and intron boundaries. This novel mechanism may
      play an important role in post-splicing events.

PMID- 11296239
TI  - SDE3 encodes an RNA helicase required for post-transcriptional gene silencing in
      Arabidopsis.
AB  - Post-transcriptional gene silencing (PTGS) provides protection in plants against
      virus infection and can suppress expression of transgenes. Arabidopsis plants
      carrying mutations at the SDE3 locus are defective in PTGS mediated by a green
      fluorescent protein transgene. However, PTGS mediated by tobacco rattle virus
      (TRV) was not affected by sde3. From these results we conclude that SDE3, like
      the previously described RNA polymerase encoded by SDE1, acts at a stage in the
      mechanism that is circumvented when PTGS is mediated by TRV. The product of SDE3
      is similar to RNA helicase-like proteins including GB110 in mouse and other
      proteins in Drosophila and humans. These proteins are similar to, but clearly
      distinct from Upf1p and SMG-2, which are required for nonsense-mediated mRNA
      decay in yeast and Caenorhabditis elegans and, in the case of SMG-2, for PTGS.

PMID- 11296240
TI  - The active sites of the influenza cap-dependent endonuclease are on different
      polymerase subunits.
AB  - The cap-dependent endonuclease of the influenza viral RNA polymerase, which
      produces the capped RNA primers that initiate viral mRNA synthesis, is comprised
      of two active sites, one for cap binding and one for endonuclease cleavage. We
      identify the amino acid sequences that constitute these two active sites and
      demonstrate that they are located on different polymerase subunits. Binding of
      the 5' terminal sequence of virion RNA (vRNA) to the polymerase activates a
      tryptophan-rich, cap-binding sequence on the PB2 subunit. At least one of the
      tryptophans functions in cap binding, indicating that this active site is
      probably similar to that of other known cap-binding proteins. Endonuclease
      cleavage, which is activated by the subsequent binding of the 3' terminal
      sequence of vRNA, resides in a PB1 sequence that contains three essential acidic
      amino acids, similar to the active sites of other enzymes that cut
      polynucleotides to produce 3'-OH ends. These results, coupled with those of our
      previous study, provide a molecular map of the five known essential active sites
      of the influenza viral polymerase.

PMID- 11296241
TI  - A 330 kb CENP-A binding domain and altered replication timing at a human
      neocentromere.
AB  - Centromere protein A (CENP-A) is an essential centromere-specific histone H3
      homologue. Using combined chromatin immunoprecipitation and DNA array analysis,
      we have defined a 330 kb CENP-A binding domain of a 10q25.3 neocentromere found
      on the human marker chromosome mardel(10). This domain is situated adjacent to
      the 80 kb region identified previously as the neocentromere site through lower
      resolution immunofluorescence/FISH analysis of metaphase chromosomes. The 330 kb
      CENP-A binding domain shows a depletion of histone H3, providing evidence for the
      replacement of histone H3 by CENP-A within centromere-specific nucleosomes. The
      DNA within this domain has a high AT-content comparable to that of alpha
      satellite, a high prevalence of LINEs and tandem repeats, and fewer SINEs and
      potential genes than the surrounding region. FISH analysis indicates that the
      normal 10q25.3 genomic region replicates around mid-S phase. Neocentromere
      formation is accompanied by a replication time lag around but not within the CENP
      A binding region, with this lag being significantly more prominent to one side.
      The availability of fully sequenced genomic markers makes human neocentromeres a
      powerful model for dissecting the functional domains of complex higher eukaryotic
      centromeres.

PMID- 11296242
TI  - Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA
      replication in Saccharomyces cerevisiae.
AB  - Cdc45, which binds to the minichromosomal maintenance (Mcm) proteins, has a
      pivotal role in the initiation and elongation steps of chromosomal DNA
      replication in eukaryotes. Here we show that throughout the cell cycle in
      Saccharomyces cerevisiae, Cdc45 forms a complex with a novel factor, Sld3.
      Consistently, Sld3 and Cdc45 associate simultaneously with replication origins in
      the chromatin immunoprecipitation assay: both proteins associate with early
      firing origins in G(1) phase and with late-firing origins in late S phase.
      Moreover, the origin associations of Sld3 and Cdc45 are mutually dependent. The
      temperature-sensitive sld3 mutation confers a defect in DNA replication at the
      restrictive temperature and reduces an interaction not only between Sld3 and
      Cdc45, but also between Cdc45 and Mcm2. These results suggest that the Sld3-Cdc45
      complex associates with replication origins through Mcm proteins. At the
      restrictive temperature in sld3-5 cells, replication factor A, a single-strand
      DNA binding protein, does not associate with origins. Therefore, the origin
      association of Sld3-Cdc45 complex is prerequisite for origin unwinding in the
      initiation of DNA replication.

PMID- 11296243
TI  - The ricinosomes of senescing plant tissue bud from the endoplasmic reticulum.
AB  - The ricinosome (synonym, precursor protease vesicle) is a novel organelle, found
      so far exclusively in plant cells. Electron microscopic studies suggest that it
      buds off from the endoplasmic reticulum in senescing tissues. Biochemical support
      for this unusual origin now comes from the composition of the purified organelle,
      which contains large amounts of a 45-kDa cysteine endoprotease precursor with a C
      terminal KDEL motif and the endoplasmic reticulum lumen residents BiP (binding
      protein) and protein disulfide isomerase. Western blot analysis, peptide
      sequencing, and mass spectrometry demonstrate retention of KDEL in the protease
      proform. Acidification of isolated ricinosomes causes castor bean cysteine
      endopeptidase activation, with cleavage of the N-terminal propeptide and the C
      terminal KDEL motif. We propose that ricinosomes accumulate during senescence by
      programmed cell death and are activated by release of protons from acidic
      vacuoles.

PMID- 11296245
TI  - Activation of a protease cascade involved in patterning the Drosophila embryo.
AB  - Dorsoventral patterning of the Drosophila embryo is initiated by a ventralizing
      signal. Production of this signal requires the serine proteases Gastrulation
      Defective (GD), Snake, and Easter, which genetic studies suggest act sequentially
      in a cascade that is activated locally in response to a ventral cue provided by
      the pipe gene. Here, we demonstrate biochemically that GD activates Snake, which
      in turn activates Easter. We also provide evidence that GD zymogen cleavage is
      important for triggering this cascade but is not spatially localized by pipe. Our
      results suggest that a broadly, rather than locally, activated protease cascade
      produces the ventralizing signal, so a distinct downstream step in this cascade
      must be spatially regulated to restrict signaling to the ventral side of the
      embryo.

PMID- 11296244
TI  - Visualization of unwinding activity of duplex RNA by DbpA, a DEAD box helicase,
      at single-molecule resolution by atomic force microscopy.
AB  - The Escherichia coli protein DbpA is unique in its subclass of DEAD box RNA
      helicases, because it possesses ATPase-specific activity toward the peptidyl
      transferase center in 23S rRNA. Although its remarkable ATPase activity had been
      well defined toward various substrates, its RNA helicase activity remained to be
      characterized. Herein, we show by using biochemical assays and atomic force
      microscopy that DbpA exhibits ATP-stimulated unwinding activity of RNA duplex
      regardless of its primary sequence. This work presents an attempt to investigate
      the action of DEAD box proteins by a single-molecule visualization methodology.
      Our atomic force microscopy images enabled us to observe directly the unwinding
      reaction of a DEAD box helicase on long stretches of double-stranded RNA.
      Specifically, we could differentiate between the binding of DbpA to RNA in the
      absence of ATP and the formation of a Y-shaped intermediate after its progression
      through double-stranded RNA in the presence of ATP. Recent studies have
      questioned the designation of DbpA, in particular, and DEAD box proteins in
      general as RNA helicases. However, accumulated evidence and the results reported
      herein suggest that these proteins are indeed helicases that resemble in many
      aspects the DNA helicases.

PMID- 11296246
TI  - Desorption/ionization on silicon (DIOS): a diverse mass spectrometry platform for
      protein characterization.
AB  - Since the advent of matrix-assisted laser desorption/ionization and electrospray
      ionization, mass spectrometry has played an increasingly important role in
      protein functional characterization, identification, and structural analysis.
      Expanding this role, desorption/ionization on silicon (DIOS) is a new approach
      that allows for the analysis of proteins and related small molecules. Despite the
      absence of matrix, DIOS-MS yields little or no fragmentation and is relatively
      tolerant of moderate amounts of contaminants commonly found in biological
      samples. Here, functional assays were performed on an esterase, a glycosidase, a
      lipase, as well as exo- and endoproteases by using enzyme-specific substrates.
      Enzyme activity also was monitored in the presence of inhibitors, successfully
      demonstrating the ability of DIOS to be used as an inhibitor screen. Because DIOS
      is a matrix-free desorption technique, it also can be used as a platform for
      multiple analyses to be performed on the same protein. This unique advantage was
      demonstrated with acetylcholine esterase for qualitative and quantitative
      characterization and also by its subsequent identification directly from the DIOS
      platform.

PMID- 11296247
TI  - Vitamin B12 and hepatitis C: molecular biology and human pathology.
AB  - Cobalamins are stored in high concentrations in the human liver and thus are
      available to participate in the regulation of hepatotropic virus functions. We
      show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry
      site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent
      manner without significantly affecting the cap-dependent mechanism. Vitamin B12
      failed to inhibit translation by IRES elements from encephalomyocarditis virus
      (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship
      between the total cobalamin concentration in human sera and HCV viral load (a
      measure of viral replication in the host). The mean viral load was two orders of
      magnitude greater when the serum cobalamin concentration was above 200 pM (P <
      0.003), suggesting that the total cobalamin concentration in an HCV-infected
      liver is biologically significant in HCV replication.

PMID- 11296249
TI  - Predicted highly expressed and putative alien genes of Deinococcus radiodurans
      and implications for resistance to ionizing radiation damage.
AB  - Predicted highly expressed (PHX) and putative alien genes determined by codon
      usages are characterized in the genome of Deinococcus radiodurans (strain R1).
      Deinococcus radiodurans (DEIRA) can survive very high doses of ionizing radiation
      that are lethal to virtually all other organisms. It has been argued that DEIRA
      is endowed with enhanced repair systems that provide protection and stability.
      However, predicted expression levels of DNA repair proteins with the exception of
      RecA tend to be low and do not distinguish DEIRA from other prokaryotes. In this
      paper, the capability of DEIRA to resist extreme doses of ionizing and UV
      radiation is attributed to an unusually high number of PHX chaperone/degradation,
      protease, and detoxification genes. Explicitly, compared with all current
      complete prokaryotic genomes, DEIRA contains the greatest number of PHX
      detoxification and protease proteins. Other sources of environmental protection
      against severe conditions of UV radiation, desiccation, and thermal effects for
      DEIRA are the several S-layer (surface structure) PHX proteins. The top PHX gene
      of DEIRA is the multifunctional tricarboxylic acid (TCA) gene aconitase, which,
      apart from its role in respiration, also alerts the cell to oxidative damage.

PMID- 11296250
TI  - On strategies for reducing greenhouse gas emissions.
AB  - Equity is of fundamental concern in the quest for international cooperation to
      stabilize greenhouse gas concentrations by the reduction of emissions. By
      modeling the carbon cycle, we estimate the global CO(2) emissions that would be
      required to stabilize the atmospheric concentration of CO(2) at levels ranging
      from 450 to 1,000 ppm. These are compared, on both an absolute and a per-capita
      basis, to scenarios for emissions from the developed and developing worlds
      generated by socio-economic models under the assumption that actions to mitigate
      greenhouse gas emissions are not taken. Need and equity have provided strong
      arguments for developing countries to request that the developed world takes the
      lead in controlling its emissions, while permitting the developing countries in
      the meantime to use primarily fossil fuels for their development. Even with major
      and early control of CO(2) emissions by the developed world, limiting
      concentration to 450 ppm implies that the developing world also would need to
      control its emissions within decades, given that we expect developing world
      emissions would otherwise double over this time. Scenarios leading to CO(2)
      concentrations of 550 ppm exhibit a reduction of the developed world's per-capita
      emission by about 50% over the next 50 years. Even for the higher stabilization
      levels considered, the developing world would not be able to use fossil fuels for
      their development in the manner that the developed world has used them.

PMID- 11296248
TI  - Electron tunneling in protein crystals.
AB  - The current understanding of electron tunneling through proteins has come from
      work on systems where donors and acceptors are held at fixed distances and
      orientations. The factors that control electron flow between proteins are less
      well understood, owing to uncertainties in the relative orientations and
      structures of the reactants during the very short time that tunneling occurs. As
      we report here, the way around such structural ambiguity is to examine oxidation
      reduction reactions in protein crystals. Accordingly, we have measured and
      analyzed the kinetics of electron transfer between native and Zn-substituted tuna
      cytochrome c (cyt c) molecules in crystals of known structure. Electron transfer
      rates [(320 s(-1) for *Zn-cyt c --> Fe(III)-cyt c; 2000 s(-1) for Fe(II)-cyt c -
      > Zn-cyt c(+))] over a Zn-Fe distance of 24.1 A closely match those for
      intraprotein electron tunneling over similar donor-acceptor separations. Our
      results indicate that van der Waals interactions and water-mediated hydrogen
      bonds are effective coupling elements for tunneling across a protein-protein
      interface.

PMID- 11296251
TI  - Similarities between the DNA replication initiators of Gram-negative bacteria
      plasmids (RepA) and eukaryotes (Orc4p)/archaea (Cdc6p).
AB  - The proteins responsible for the initiation of DNA replication are thought to be
      essentially unrelated in bacteria and archaea/eukaryotes. Here we show that RepA,
      the initiator from the Pseudomonas plasmid pPS10, and the C-terminal domain of
      ScOrc4p, a subunit of Saccharomyces cerevisiae (Sc) origin recognition complex
      (ORC), share sequence similarities. Based on biochemical and spectroscopic
      evidence, these similarities include common structural elements, such as a winged
      helix domain and a leucine-zipper dimerization motif. We have also found that
      ScOrc4p, as previously described for RepA-type initiators, interacts with
      chaperones of the Hsp70 family both in vitro and in vivo, most probably to
      regulate the assembly of active ORC. In evolutionary terms, our results are
      compatible with the recruitment of the same protein module for initiation of DNA
      replication by the ancestors of present-day Gram-negative bacteria plasmids,
      archaea, and eukaryotes.

PMID- 11296252
TI  - Comparative assessment of virulence of recombinant vaccinia viruses expressing IL
      2 and IL-15 in immunodeficient mice.
AB  - IL-2 and -15 belong to the four alpha-helix bundle family of cytokines and
      display a spectrum of overlapping immune functions because of shared signal
      transducing receptor components of the IL-2 receptor complex. However, recent
      evidence suggests a nonredundant unique role for IL-15 in the establishment and
      perhaps maintenance of peripheral natural killer (NK) cell populations in vivo.
      To explore the contribution of locally released IL-15 on peripheral NK-cell
      mediated innate immune responses, we generated a recombinant vaccinia virus that
      expresses IL-15 and evaluated the course of vaccinial disease in athymic nude
      mice. Coexpression of IL-15 resulted in the attenuation of virulence of vaccinia
      virus, and mice inoculated with 10(5) plaque-forming units or less resolved the
      infection successfully. In contrast, mice inoculated with a similar dose of the
      control vaccinia virus failed to eliminate the virus and died of generalized
      vaccinial disease. Enhanced expression of IL-12 and IFN-gamma as well as
      induction of chemokines were evident in the mice inoculated with IL-15-expressing
      vaccinia virus in addition to an increase in NK cells in the spleen. However, in
      this model system, the degree of attenuation in viral virulence attained with
      coexpression of IL-15 was much less than that achieved with coexpression of IL-2,
      suggesting that the peripheral NK-cell-mediated events are more responsive to IL
      2 than to IL-15.

PMID- 11296253
TI  - RNA tertiary interactions in the large ribosomal subunit: the A-minor motif.
AB  - Analysis of the 2.4-A resolution crystal structure of the large ribosomal subunit
      from Haloarcula marismortui reveals the existence of an abundant and ubiquitous
      structural motif that stabilizes RNA tertiary and quaternary structures. This
      motif is termed the A-minor motif, because it involves the insertion of the
      smooth, minor groove edges of adenines into the minor groove of neighboring
      helices, preferentially at C-G base pairs, where they form hydrogen bonds with
      one or both of the 2' OHs of those pairs. A-minor motifs stabilize contacts
      between RNA helices, interactions between loops and helices, and the
      conformations of junctions and tight turns. The interactions between the 3'
      terminal adenine of tRNAs bound in either the A site or the P site with 23S rRNA
      are examples of functionally significant A-minor interactions. The A-minor motif
      is by far the most abundant tertiary structure interaction in the large ribosomal
      subunit; 186 adenines in 23S and 5S rRNA participate, 68 of which are conserved.
      It may prove to be the universally most important long-range interaction in large
      RNA structures.

PMID- 11296254
TI  - Carcinogen-specific induction of genetic instability.
AB  - It has been proposed recently that the type of genetic instability in cancer
      cells reflects the selection pressures exerted by specific carcinogens. We have
      tested this hypothesis by treating immortal, genetically stable human cells with
      representative carcinogens. We found that cells resistant to the bulky-adduct
      forming agent 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) exhibited a
      chromosomal instability (CIN), whereas cells resistant to the methylating agent N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG) exhibited a microsatellite instability
      (MIN) associated with mismatch repair defects. Conversely, we found that cells
      purposely made into CIN cells are resistant to PhIP, whereas MIN cells are
      resistant to MNNG. These data demonstrate that exposure to specific carcinogens
      can indeed select for tumor cells with distinct forms of genetic instability and
      vice versa.

PMID- 11296255
TI  - On the role of the K-proton transfer pathway in cytochrome c oxidase.
AB  - Cytochrome c oxidase is a membrane-bound enzyme that catalyzes the four-electron
      reduction of oxygen to water. This highly exergonic reaction drives proton
      pumping across the membrane. One of the key questions associated with the
      function of cytochrome c oxidase is how the transfer of electrons and protons is
      coupled and how proton transfer is controlled by the enzyme. In this study we
      focus on the function of one of the proton transfer pathways of the R.
      sphaeroides enzyme, the so-called K-proton transfer pathway (containing a highly
      conserved Lys(I-362) residue), leading from the protein surface to the catalytic
      site. We have investigated the kinetics of the reaction of the reduced enzyme
      with oxygen in mutants of the enzyme in which a residue [Ser(I-299)] near the
      entry point of the pathway was modified with the use of site-directed
      mutagenesis. The results show that during the initial steps of oxygen reduction,
      electron transfer to the catalytic site (to form the "peroxy" state, P(r))
      requires charge compensation through the proton pathway, but no proton uptake
      from the bulk solution. The charge compensation is proposed to involve a movement
      of the K(I-362) side chain toward the binuclear center. Thus, in contrast to what
      has been assumed previously, the results indicate that the K-pathway is used
      during oxygen reduction and that K(I-362) is charged at pH approximately 7.5. The
      movement of the Lys is proposed to regulate proton transfer by "shutting off" the
      protonic connectivity through the K-pathway after initiation of the O(2)
      reduction chemistry. This "shutoff" prevents a short-circuit of the proton
      pumping machinery of the enzyme during the subsequent reaction steps.

PMID- 11296256
TI  - DNA polymerase epsilon is required for coordinated and efficient chromosomal DNA
      replication in Xenopus egg extracts.
AB  - DNA polymerase epsilon (Pol epsilon) is thought to be involved in DNA
      replication, repair, and cell-cycle checkpoint control in eukaryotic cells.
      Although the requirement of other replicative DNA polymerases, DNA polymerases
      alpha and delta (Pol alpha and delta), for chromosomal DNA replication has been
      well documented by genetic and biochemical studies, the precise role, if any, of
      Pol epsilon in chromosomal DNA replication is still obscure. Here we show, with
      the use of a cell-free replication system with Xenopus egg extracts, that Xenopus
      Pol epsilon is indeed required for chromosomal DNA replication. In Pol epsilon
      depleted extracts, the elongation step of chromosomal DNA replication is markedly
      impaired, resulting in significant reduction of the overall DNA synthesis as well
      as accumulation of small replication intermediates. Moreover, despite the
      decreased DNA synthesis, excess amounts of Pol alpha are loaded onto the
      chromatin template in Pol epsilon-depleted extracts, indicative of the failure of
      proper assembly of DNA synthesis machinery at the fork. These findings strongly
      suggest that Pol epsilon, along with Pol alpha and Pol delta, is necessary for
      coordinated chromosomal DNA replication in eukaryotic cells.

PMID- 11296257
TI  - Activation-dependent changes in receptor distribution and dendritic morphology in
      hippocampal neurons expressing P2X2-green fluorescent protein receptors.
AB  - ATP-gated P2X(2) receptors are widely expressed in neurons, but the cellular
      effects of receptor activation are unclear. We engineered functional green
      fluorescent protein (GFP)-tagged P2X(2) receptors and expressed them in embryonic
      hippocampal neurons, and report an approach to determining functional and total
      receptor pool sizes in living cells. ATP application to dendrites caused receptor
      redistribution and the formation of varicose hot spots of higher P2X(2)-GFP
      receptor density. Redistribution in dendrites was accompanied by an activation
      dependent enhancement of the ATP-evoked current. Substate-specific mutant T18A
      P2X(2)-GFP receptors showed no redistribution or activation-dependent enhancement
      of the ATP-evoked current. Thus fluorescent P2X(2)-GFP receptors function
      normally, can be quantified, and reveal the dynamics of P2X(2) receptor
      distribution on the seconds time scale.

PMID- 11296259
TI  - Systemic spread of an RNA insect virus in plants expressing plant viral movement
      protein genes.
AB  - Flock house virus (FHV), a single-stranded RNA insect virus, has previously been
      reported to cross the kingdom barrier and replicate in barley protoplasts and in
      inoculated leaves of several plant species [Selling, B. H., Allison, R. F. &
      Kaesberg, P. (1990) Proc. Natl. Acad. Sci. USA 87, 434-438]. There was no
      systemic movement of FHV in plants. We tested the ability of movement proteins
      (MPs) of plant viruses to provide movement functions and cause systemic spread of
      FHV in plants. We compared the growth of FHV in leaves of nontransgenic and
      transgenic plants expressing the MP of tobacco mosaic virus or red clover
      necrotic mosaic virus (RCNMV). Both MPs mobilized cell-to-cell and systemic
      movement of FHV in Nicotiana benthamiana plants. The yield of FHV was more than
      100-fold higher in the inoculated leaves of transgenic plants than in the
      inoculated leaves of nontransgenic plants. In addition, FHV accumulated in the
      noninoculated upper leaves of both MP-transgenic plants. RCNMV MP was more
      efficient in mobilizing FHV to noninoculated upper leaves. We also report here
      that FHV replicates in inoculated leaves of six additional plant species:
      alfalfa, Arabidopsis, Brassica, cucumber, maize, and rice. Our results
      demonstrate that plant viral MPs cause cell-to-cell and long-distance movement of
      an animal virus in plants and offer approaches to the study of the evolution of
      viruses and mechanisms governing mRNA trafficking in plants as well as to the
      development of promising vectors for transient expression of foreign genes in
      plants.

PMID- 11296258
TI  - Functional disorders of the sympathetic nervous system in mice lacking the alpha
      1B subunit (Cav 2.2) of N-type calcium channels.
AB  - N-type voltage-dependent Ca(2+) channels (VDCCs), predominantly localized in the
      nervous system, have been considered to play an essential role in a variety of
      neuronal functions, including neurotransmitter release at sympathetic nerve
      terminals. As a direct approach to elucidating the physiological significance of
      N-type VDCCs, we have generated mice genetically deficient in the alpha(1B)
      subunit (Ca(v) 2.2). The alpha(1B)-deficient null mice, surprisingly, have a
      normal life span and are free from apparent behavioral defects. A complete and
      selective elimination of N-type currents, sensitive to omega-conotoxin GVIA, was
      observed without significant changes in the activity of other VDCC types in
      neuronal preparations of mutant mice. The baroreflex response, mediated by the
      sympathetic nervous system, was markedly reduced after bilateral carotid
      occlusion. In isolated left atria prepared from N-type-deficient mice, the
      positive inotropic responses to electrical sympathetic neuronal stimulation were
      dramatically decreased compared with those of normal mice. In contrast,
      parasympathetic nervous activity in the mutant mice was nearly identical to that
      of wild-type mice. Interestingly, the mutant mice showed sustained elevation of
      heart rate and blood pressure. These results provide direct evidence that N-type
      VDCCs are indispensable for the function of the sympathetic nervous system in
      circulatory regulation and indicate that N-type VDCC-deficient mice will be a
      useful model for studying disorders attributable to sympathetic nerve
      dysfunction.

PMID- 11296260
TI  - Muscle-regulated expression and determinants for neuromuscular junctional
      localization of the mouse RIalpha regulatory subunit of cAMP-dependent protein
      kinase.
AB  - In skeletal muscle, transcription of the gene encoding the mouse type Ialpha
      (RIalpha) subunit of the cAMP-dependent protein kinase is initiated from the
      alternative noncoding first exons 1a and 1b. Here, we report that activity of the
      promoter upstream of exon 1a (Pa) depends on two adjacent E boxes (E1 and E2) in
      NIH 3T3-transfected fibroblasts as well as in intact muscle. Both basal activity
      and MyoD transactivation of the Pa promoter require binding of the upstream
      stimulating factors (USF) to E1. E2 binds either an unknown protein in a USF/E1
      complex-dependent manner or MyoD. Both E2-bound proteins seem to function as
      repressors, but with different strengths, of the USF transactivation potential.
      Previous work has shown localization of the RIalpha protein at the neuromuscular
      junction. Using DNA injection into muscle of plasmids encoding segments of
      RIalpha or RIIalpha fused to green fluorescent protein, we demonstrate that
      anchoring at the neuromuscular junction is specific to RIalpha subunits and
      requires the amino-terminal residues 1-81. Mutagenesis of Phe-54 to Ala in the
      full-length RIalpha-green fluorescent protein template abolishes localization,
      indicating that dimerization of RIalpha is essential for anchoring. Moreover, two
      other hydrophobic residues, Val-22 and Ile-27, are crucial for localization of
      RIalpha at the neuromuscular junction. These amino acids are involved in the
      interaction of the Caenorhabditis elegans type Ialpha homologue R(CE) with
      AKAP(CE) and for in vitro binding of RIalpha to dual A-kinase anchoring protein
      1. We also show enrichment of dual A-kinase anchoring protein 1 at the
      neuromuscular junction, suggesting that it could be responsible for RIalpha
      tethering at this site.

PMID- 11296261
TI  - In vivo detection of gene expression in liver by 31P nuclear magnetic resonance
      spectroscopy employing creatine kinase as a marker gene.
AB  - In vivo assessment of gene expression is desirable to obtain information on the
      extent and duration of transduction of tissue after gene delivery. We have
      developed an in vivo, potentially noninvasive, method for detecting virally
      mediated gene transfer to the liver. The method employs an adenoviral vector
      carrying the gene for the brain isozyme of murine creatine kinase (CK-B), an ATP
      buffering enzyme expressed mainly in muscle and brain but absent from liver,
      kidney, and pancreas. Gene expression was monitored by (31)P magnetic resonance
      spectroscopy (MRS) using the product of the CK enzymatic reaction,
      phosphocreatine, as an indicator of transfection. The vector was administered
      into nude mice by tail vein injection, and exogenous creatine was administered in
      the drinking water and by i.p. injection of 2% creatine solution before (31)P MRS
      examination, which was performed on surgically exposed livers. A phosphocreatine
      resonance was detected in livers of mice injected with the vector and was absent
      from livers of control animals. CK expression was confirmed in the injected
      animals by Western blot analysis, enzymatic assays, and immunofluorescence
      measurements. We conclude that the syngeneic enzyme CK can be used as a marker
      gene for in vivo monitoring of gene expression after virally mediated gene
      transfer to the liver.

PMID- 11296262
TI  - Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma.
AB  - Airway hyperresponsiveness (AHR), goblet cell metaplasia, and mucus
      overproduction are important features of bronchial asthma. To elucidate the
      molecular mechanisms behind these pulmonary pathologies, we examined for genes
      preferentially expressed in the lungs of a murine model of allergic asthma by
      using suppression subtractive hybridization (SSH). We identified a gene called
      gob-5 that had a selective expression pattern in the airway epithelium with AHR.
      Here, we show that gob-5, a member of the calcium-activated chloride channel
      family, is a key molecule in the induction of murine asthma. Intratracheal
      administration of adenovirus-expressing antisense gob-5 RNA into AHR-model mice
      efficiently suppressed the asthma phenotype, including AHR and mucus
      overproduction. In contrast, overexpression of gob-5 in airway epithelia by using
      an adenoviral vector exacerbated the asthma phenotype. Introduction of either gob
      5 or hCLCA1, the human counterpart of gob-5, into the human mucoepidermoid cell
      line NCI-H292 induced mucus production as well as MUC5AC expression. Our results
      indicated that gob-5 may play a critical role in murine asthma, and its human
      counterpart hCLCA1 is therefore a potential target for asthma therapy.

PMID- 11296263
TI  - Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides
      Abeta 42 and Abeta 40 in vitro and in vivo.
AB  - Recent epidemiological studies show a strong reduction in the incidence of
      Alzheimer's disease in patients treated with cholesterol-lowering statins.
      Moreover, elevated Abeta42 levels and the varepsilon4 allele of the lipid-carrier
      apolipoprotein E are regarded as risk factors for sporadic and familial
      Alzheimer's disease. Here we demonstrate that the widely used cholesterol
      lowering drugs simvastatin and lovastatin reduce intracellular and extracellular
      levels of Abeta42 and Abeta40 peptides in primary cultures of hippocampal neurons
      and mixed cortical neurons. Likewise, guinea pigs treated with high doses of
      simvastatin showed a strong and reversible reduction of cerebral Abeta42 and
      Abeta40 levels in the cerebrospinal fluid and brain homogenate. These results
      suggest that lipids are playing an important role in the development of
      Alzheimer's disease. Lowered levels of Abeta42 may provide the mechanism for the
      observed reduced incidence of dementia in statin-treated patients and may open up
      avenues for therapeutic interventions.

PMID- 11296264
TI  - Gamma-aminobutyric acid type A receptors modulate cAMP-mediated long-term
      potentiation and long-term depression at monosynaptic CA3-CA1 synapses.
AB  - cAMP induces a protein-synthesis-dependent late phase of long-term potentiation
      (LTP) at CA3-CA1 synapses in acute hippocampal slices. Herein we report cAMP
      mediated LTP and long-term depression (LTD) at monosynaptic CA3-CA1 cell pairs in
      organotypic hippocampal slice cultures. After bath application of the membrane
      permeable cAMP analog adenosine 3',5'-cyclic monophosphorothioate, Sp isomer (Sp
      cAMPS), synaptic transmission was enhanced for at least 2 h. Consistent with
      previous findings, the late phase of LTP requires activation of cAMP-dependent
      protein kinase A and protein synthesis. There is also an early phase of LTP
      induced by cAMP; the early phase depends on protein kinase A but, in contrast to
      the later phase, does not require protein synthesis. In addition, the cAMP
      induced LTP is associated with a reduction of paired-pulse facilitation,
      suggesting that presynaptic modification may be involved. Furthermore, we found
      that Sp-cAMPS induced LTD in slices pretreated with picrotoxin, a gamma
      aminobutyric acid type A (GABA(A)) receptor antagonist. This form of LTD depends
      on protein synthesis and protein phosphatase(s) and is accompanied by an
      increased ratio of failed synaptic transmission. These results suggest that
      GABA(A) receptors can modulate the effect of cAMP on synaptic transmission and
      thus determine the direction of synaptic plasticity.

PMID- 11296265
TI  - Gene discovery and gene function assignment in filamentous fungi.
AB  - Filamentous fungi are a large group of diverse and economically important
      microorganisms. Large-scale gene disruption strategies developed in budding yeast
      are not applicable to these organisms because of their larger genomes and lower
      rate of targeted integration (TI) during transformation. We developed transposon
      arrayed gene knockouts (TAGKO) to discover genes and simultaneously create gene
      disruption cassettes for subsequent transformation and mutant analysis.
      Transposons carrying a bacterial and fungal drug resistance marker are used to
      mutagenize individual cosmids or entire libraries in vitro. Cosmids are annotated
      by DNA sequence analysis at the transposon insertion sites, and cosmid inserts
      are liberated to direct insertional mutagenesis events in the genome. Based on
      saturation analysis of a cosmid insert and insertions in a fungal cosmid library,
      we show that TAGKO can be used to rapidly identify and mutate genes. We further
      show that insertions can create alterations in gene expression, and we have used
      this approach to investigate an amino acid oxidation pathway in two important
      fungal phytopathogens.

PMID- 11296266
TI  - Tracking memory's trace.
AB  - There is strong converging evidence that the intermediate and medial part of the
      hyperstriatum ventrale of the chick brain is a memory store for information
      acquired through the learning process of imprinting. Neurons in this memory
      system come, through imprinting, to respond selectively to the imprinting
      stimulus (IS) neurons and so possess the properties of a memory trace. Therefore,
      the responses of the intermediate and medial part of the hyperstriatum ventrale
      neurons to a visual imprinting stimulus were determined before, during, and after
      training. Of the total recorded population, the proportions of IS neurons shortly
      after each of two 1-h training sessions were significantly higher (approximately
      2 times) than the pretraining proportion. However, approximately 4.5 h later this
      proportion had fallen significantly and did not differ significantly from the
      pretraining proportion. Nevertheless, approximately 21.5 h after the end of
      training, the proportion of IS neurons was at its highest (approximately 3 times
      the pretraining level). No significant fluctuations occurred in the proportions
      of neurons responding to the alternative stimulus. In addition, nonmonotonic
      changes were found commonly in the activity of 230 of the neurons tracked
      individually from before training to shortly after the end of training. Thus the
      pattern of change in responsiveness both at the population level and at the level
      of individual neurons was highly nonmonotonic. Such a pattern of change is not
      consistent with simple models of memory based on synaptic strengthening to
      asymptote. A model is proposed that accounts for the changes in the population
      responses to the imprinting stimulus in terms of changes in the responses of
      individual neurons.

PMID- 11296267
TI  - Even-odd alternation in mass spectrum of thymine and uracil clusters: evidence of
      intracluster photodimerization.
AB  - Multiphoton ionization of thymine and uracil clusters generated by a supersonic
      molecular beam gave rise to a remarkable alternation of mass spectral intensities
      between even- and odd-numbered clusters. Such alternation was observed in
      clusters of up to 30 molecules. Excitation to the two lowest electronically
      excited states seemed to be a strong prerequisite. In view of the well known
      photodimerization reaction of thymine and uracil in the bulk phase, it is
      proposed that such alternation in the mass spectral intensity resulted from
      formation of photodimer units within the cluster on intense UV irradiation.
      Several analogues of thymine with no known propensity for photodimerization in
      the bulk phase did not exhibit any sign of such alternation in the cluster mass
      spectrum. The intrinsic UV window for photodimerization, and hence photoinduced
      mammalian mutagenesis, was estimated to be approximately 210-280 nm,
      significantly narrower than the previously reported bulk values of 150-300 nm.

PMID- 11296268
TI  - Overexpression of 5-methylcytosine DNA glycosylase in human embryonic kidney
      cells EcR293 demethylates the promoter of a hormone-regulated reporter gene.
AB  - We have shown that the DNA demethylation complex isolated from chicken embryos
      has a G(.)T mismatch DNA glycosylase that also possesses 5-methylcytosine DNA
      glycosylase (5-MCDG) activity. Herein we show that human embryonic kidney cells
      stably transfected with 5-MCDG cDNA linked to a cytomegalovirus promoter
      overexpress 5-MCDG. A 15- to 20-fold overexpression of 5-MCDG results in the
      specific demethylation of a stably integrated ecdysone-retinoic acid responsive
      enhancer-promoter linked to a beta-galactosidase reporter gene. Demethylation
      occurs in the absence of the ligand ponasterone A (an analogue of ecdysone). The
      state of methylation of the transgene was investigated by Southern blot analysis
      and by the bisulfite genomic sequencing reaction. Demethylation occurs downstream
      of the hormone response elements. No genome-wide demethylation was observed. The
      expression of an inactive mutant of 5-MCDG or the empty vector does not elicit
      any demethylation of the promoter-enhancer of the reporter gene. An increase in 5
      MCDG activity does not influence the activity of DNA methyltransferase(s) when
      tested in vitro with a hemimethylated substrate. There is no change in the
      transgene copy number during selection of the clones with antibiotics.
      Immunoprecipitation combined with Western blot analysis showed that an antibody
      directed against 5-MCDG precipitates a complex containing the retinoid X receptor
      alpha. The association between retinoid receptor and 5-MCDG is not ligand
      dependent. These results suggest that a complex of the hormone receptor with 5
      MCDG may target demethylation of the transgene in this system.

PMID- 11296269
TI  - In vivo restoration of laminin 5 beta 3 expression and function in junctional
      epidermolysis bullosa.
AB  - The blistering disorder, lethal junctional epidermolysis bullosa (JEB), can
      result from mutations in the LAMB3 gene, which encodes laminin 5 beta3 (beta3).
      Appropriate expression of LAMbeta3 in JEB skin tissue could potentially
      ameliorate the symptoms of the underlying disease. To explore the utility of this
      therapeutic approach, primary keratinocytes from six unrelated JEB patients were
      transduced with a retroviral vector encoding beta3 and used to regenerate human
      skin on severe combined immunodeficient (SCID) mice. Tissue regenerated from
      beta3-transduced JEB keratinocytes produced phenotypically normal skin
      characterized by sustained beta3 expression and the formation of hemidesmosomes.
      Additionally, beta3 gene transfer corrected the distribution of a number of
      important basement membrane zone proteins including BPAG2, integrins beta4/beta1,
      and laminins alpha3/gamma2. Skin produced from beta3-negative (beta3[-]) JEB
      cells mimicked the hallmarks of the disease state and did not exhibit any of the
      aforementioned traits. Therefore, by effecting therapeutic gene transfer to beta3
      deficient primary keratinocytes, it is possible to produce healthy, normal skin
      tissue in vivo. These data support the utility of gene therapy for JEB and
      highlight the potential for gene delivery in the treatment of human genetic skin
      disease.

PMID- 11296270
TI  - Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2.
AB  - We have previously described how T and natural killer (NK) lineage commitment
      proceeds from common T/NK progenitors (p-T/NK) in the murine fetal thymus (FT),
      with the use of a clonal assay system capable of discriminating p-T/NK from
      unipotent T or NK lineage-committed progenitors (p-T and p-NK, respectively). The
      molecular mechanisms controlling the commitment processes, however, are yet to be
      defined. In this study, we investigated the progenitor activity of FT cells from
      Id2-/- mice that exhibit defective NK cell development. In the Id2-/- FT, NK
      cells were greatly reduced, and a cell population that exclusively contains p-NK
      in the wild-type thymus was completely missing. Id2-/- FT progenitors were unable
      to differentiate into NK cells in IL-2-supplemented-FT organ culture. Single
      progenitor analysis demonstrated that all Id2-/- fetal thymic progenitors are
      destined for the T cell lineage, whereas progenitors for T/NK, T, and NK cell
      lineages were found in the control. Interestingly, the total progenitor number
      was similar between Id2-/- and Id2+/+ embryos analyzed. Expression of Id2 was
      correlated with p-NK activity. Our results suggest that Id2 is indispensable in
      thymic NK cell development, where it most probably restricts bipotent T/NK
      progenitors to the NK cell lineage.

PMID- 11296271
TI  - Applied molecular evolution of O6-benzylguanine-resistant DNA alkyltransferases
      in human hematopoietic cells.
AB  - Applied molecular evolution is a rapidly developing technology that can be used
      to create and identify novel enzymes that nature has not selected. An important
      application of this technology is the creation of highly drug-resistant enzymes
      for cancer gene therapy. Seventeen O(6)-alkylguanine-DNA alkyltransferase (AGT)
      mutants highly resistant to O(6)-benzylguanine (BG) were identified previously by
      screening 8 million variants, using genetic complementation in Escherichia coli.
      To examine the potential of these mutants for use in humans, the sublibrary of
      AGT clones was introduced to human hematopoietic cells and stringently selected
      for resistance to killing by the combination of BG and 1,3-bis(2-chloroethyl)-1
      nitrosourea. This competitive analysis between the mutants in human cells
      revealed three AGT mutants that conferred remarkable resistance to the
      combination of BG and 1,3-bis(2-chloroethyl)-1-nitrosourea. Of these, one was
      recovered significantly more frequently than the others. Upon further analysis,
      this mutant displayed a level of BG resistance in human hematopoietic cells
      greater than that of any previously reported mutant.

PMID- 11296274
TI  - Networking proteins in yeast.

PMID- 11296275
TI  - Circumventing leptin resistance for weight control.

PMID- 11296276
TI  - Who's got pull around here? Cell organization in development and tissue
      engineering.

PMID- 11296277
TI  - New transformation tricks from a barnyard retrovirus: implications for human lung
      cancer.

PMID- 11296279
TI  - Biological diversity and resource plunder in the geological record: casual
      correlations or causal relationships?

PMID- 11296278
TI  - Delivering messages from the 3' end.

PMID- 11296280
TI  - Retroviruses and the pathogenesis of schizophrenia.

PMID- 11296281
TI  - Global biodiversity and the ancient carbon cycle.
AB  - Paleontological data for the diversity of marine animals and land plants are
      shown to correlate significantly with a concurrent measure of stable carbon
      isotope fractionation for approximately the last 400 million years. The
      correlations can be deduced from the assumption that increasing plant diversity
      led to increasing chemical weathering of rocks and therefore an increasing flux
      of carbon from the atmosphere to rocks, and nutrients from the continents to the
      oceans. The CO(2) concentration dependence of photosynthetic carbon isotope
      fractionation then indicates that the diversification of land plants led to
      decreasing CO(2) levels, while the diversification of marine animals derived from
      increasing nutrient availability. Under the explicit assumption that global
      biodiversity grows with global biomass, the conservation of carbon shows that the
      long-term fluctuations of CO(2) levels were dominated by complementary changes in
      the biological and fluid reservoirs of carbon, while the much larger geological
      reservoir remained relatively constant in size. As a consequence, the
      paleontological record of biodiversity provides an indirect estimate of the
      fluctuations of ancient CO(2) levels.

PMID- 11296282
TI  - A molecular analysis of dietary diversity for three archaic Native Americans.
AB  - DNA was extracted from three fecal samples, more than 2,000 years old, from Hinds
      Cave, Texas. Amplification of human mtDNA sequences showed their affiliation with
      contemporary Native Americans, while sequences from pronghorn antelope, bighorn
      sheep, and cottontail rabbit allowed these animals to be identified as part of
      the diet of these individuals. Furthermore, amplification of chloroplast DNA
      sequences identified eight different plants as dietary elements. These archaic
      humans consumed 2-4 different animal species and 4-8 different plant species
      during a short time period. The success rate for retrieval of DNA from paleofeces
      is in strong contrast to that from skeletal remains where the success rate is
      generally low. Thus, human paleofecal remains represent a source of ancient DNA
      that significantly complements and may in some cases be superior to that from
      skeletal tissue.

PMID- 11296283
TI  - Toward rules for 1:1 polyamide:DNA recognition.
AB  - Polyamides composed of four amino acids, imidazole (Im), pyrrole (Py),
      hydroxypyrrole (Hp), and beta-alanine (beta), are synthetic ligands that form
      highly stable complexes in the minor groove of DNA. Although specific pairing
      rules within the 2:1 motif can be used to distinguish the four Watson. Crick base
      pairs, a comparable recognition code for 1:1 polyamide:DNA complexes had not been
      described. To set a quantitative baseline for the field, the sequence
      specificities of Im, Py, Hp, and beta for the four Watson. Crick base pairs were
      determined for two polyamides, Im-beta-ImPy-beta-Im-beta-ImPy-beta-Dp (1, for Im,
      Py, and beta) and Im-beta-ImHp-beta-Im-beta-ImPy-beta-Dp (2, for Hp), in a 1:1
      complex within the DNA sequence context 5'-AAAGAGAAGAG-3'. Im residues do not
      distinguish G,C from A,T but bind all four base pairs with high affinity. Py and
      beta residues exhibit > or = 10-fold preference for A,T over G,C base pairs. The
      Hp residue displays a unique preference for a single A.T base pair with an
      energetic penalty.

PMID- 11296284
TI  - The thermodynamic origin of the stability of a thermophilic ribozyme.
AB  - Understanding the mechanism of thermodynamic stability of an RNA structure has
      significant implications for the function and design of RNA. We investigated the
      equilibrium folding of a thermophilic ribozyme and its mesophilic homologue by
      using hydroxyl radical protection, small-angle x-ray scattering, and circular
      dichroism. Both RNAs require Mg(2+) to fold to their native structures that are
      very similar. The stability is measured as a function of Mg(2+) and urea
      concentrations at different temperatures. The enhanced stability of the
      thermophilic ribozyme primarily is derived from a tremendous increase in the
      amount of structure formed in the ultimate folding transition. This increase in
      structure formation and cooperativity arises because the penultimate and the
      ultimate folding transitions in the mesophilic ribozyme become linked into a
      single transition in the folding of the thermophilic ribozyme. Therefore, the
      starting point, or reference state, for the transition to the native, functional
      thermophilic ribozyme is significantly less structured. The shift in the
      reference state, and the resulting increase in folding cooperativity, is likely
      due to the stabilization of selected native interactions that only form in the
      ultimate transition. This mechanism of using a less structured intermediate and
      increased cooperativity to achieve higher functional stability for tertiary RNAs
      is fundamentally different from that commonly proposed to explain the increased
      stability of thermophilic proteins.

PMID- 11296285
TI  - Prediction of protein deamidation rates from primary and three-dimensional
      structure.
AB  - A method for the quantitative estimation of instability with respect to
      deamidation of the asparaginyl (Asn) residues in proteins is described. The
      procedure involves the observation of several simple aspects of the three
      dimensional environment of each Asn residue in the protein and a calculation that
      includes these observations, the primary amino acid residue sequence, and the
      previously reported complete set of sequence-dependent rates of deamidation for
      Asn pentapeptides. This method is demonstrated and evaluated for 23 proteins in
      which 31 unstable and 167 stable Asn residues have been reported and for 7
      unstable and 63 stable Asn residues that have been reported in 61 human
      hemoglobin variants. The relative importance of primary structure and three
      dimensional structure in Asn deamidation is estimated.

PMID- 11296286
TI  - Ligand-independent oligomerization of cell-surface erythropoietin receptor is
      mediated by the transmembrane domain.
AB  - Binding of erythropoietin (Epo) to the Epo receptor (EpoR) is crucial for
      production of mature red cells. Although it is well established that the Epo
      bound EpoR is a dimer, it is not clear whether, in the absence of ligand, the
      intact EpoR is a monomer or oligomer. Using antibody-mediated immunofluorescence
      copatching (oligomerizing) of epitope-tagged receptors at the surface of live
      cells, we show herein that a major fraction of the full-length murine EpoR exists
      as preformed dimers/oligomers in BOSC cells, which are human embryo kidney 293T
      derived cells. This observed oligomerization is specific because, under the same
      conditions, epitope-tagged EpoR did not oligomerize with several other tagged
      receptors (thrombopoietin receptor, transforming growth factor beta receptor type
      II, or prolactin receptor). Strikingly, the EpoR transmembrane (TM) domain but
      not the extracellular or intracellular domains enabled the prolactin receptor to
      copatch with EpoR. Preformed EpoR oligomers are not constitutively active and Epo
      binding was required to induce signaling. In contrast to tyrosine kinase
      receptors (e.g., insulin receptor), which cannot signal when their TM domain is
      replaced by the strongly dimerizing TM domain of glycophorin A, the EpoR could
      tolerate the replacement of its TM domain with that of glycophorin A and retained
      signaling. We propose a model in which TM domain-induced dimerization maintains
      unliganded EpoR in an inactive state that can readily be switched to an active
      state by physiologic levels of Epo.

PMID- 11296287
TI  - Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored
      cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of
      which mediates oncogenic transformation.
AB  - Jaagsiekte sheep retrovirus (JSRV) can induce rapid, multifocal lung cancer, but
      JSRV is a simple retrovirus having no known oncogenes. Here we show that the
      envelope (env) gene of JSRV has the unusual property that it can induce
      transformation in rat fibroblasts, and thus is likely to be responsible for
      oncogenesis in animals. Retrovirus entry into cells is mediated by Env
      interaction with particular cell-surface receptors, and we have used phenotypic
      screening of radiation hybrid cell lines to identify the candidate lung cancer
      tumor suppressor HYAL2/LUCA2 as the receptor for JSRV. HYAL2 was previously
      described as a lysosomal hyaluronidase, but we show that HYAL2 is actually a
      glycosylphosphatidylinositol (GPI)-anchored cell-surface protein. Furthermore, we
      could not detect hyaluronidase activity associated with or secreted by cells
      expressing HYAL2, whereas we could easily detect such activity from cells
      expressing the related serum hyaluronidase HYAL1. Although the function of HYAL2
      is currently unknown, other GPI-anchored proteins are involved in signal
      transduction, and some mediate mitogenic responses, suggesting a potential role
      of HYAL2 in JSRV Env-mediated oncogenesis. Lung cancer induced by JSRV closely
      resembles human bronchiolo-alveolar carcinoma, a disease that is increasing in
      frequency and now accounts for approximately 25% of all lung cancer. The finding
      that JSRV env is oncogenic and the identification of HYAL2 as the JSRV receptor
      provide tools for further investigation of the mechanism of JSRV oncogenesis and
      its relationship to human bronchiolo-alveolar carcinoma.

PMID- 11296288
TI  - Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA.
AB  - Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary
      carcinoma, a unique animal model for human bronchioalveolar carcinoma. We
      previously isolated a JSRV proviral clone and showed that it was both infectious
      and oncogenic. Thus JSRV is necessary and sufficient for the development of ovine
      pulmonary carcinoma, but no data are available on the mechanisms of
      transformation. Inspection of the JSRV genome reveals standard retroviral genes,
      but no evidence for a viral oncogene. However, an alternate ORF in pol (orf-x)
      might be a candidate for a transforming gene. We tested whether the JSRV genome
      might encode a transforming gene by transfecting an expression plasmid for JSRV
      [pCMVJS21, driven by the cytomegalovirus (CMV) immediate early promoter] into
      mouse NIH 3T3 cells. Foci of transformed cells appeared in the transfected
      cultures 2-3 weeks posttransfection; cloned transformants showed anchorage
      independence for growth, and they expressed JSRV RNA. These results indicate that
      the JRSV genome contains information with direct transforming potential for NIH
      3T3 cells. Transfection of a mutated version of pCMVJS21 in which the orf-x
      protein was terminated by two stop codons also gave transformed foci. Thus, orf-x
      was eliminated as the candidate transforming gene. In addition, another
      derivative of pCMVJS21 (pCMVJS21DeltaGP) in which the gag, pol (and orf-x) coding
      sequences were deleted also gave transformed foci. These results indicate that
      the envelope gene carries the transforming potential. This is an unusual example
      of a native retroviral structural protein with transformation potential.

PMID- 11296289
TI  - Cessation of rapid late endosomal tubulovesicular trafficking in Niemann-Pick
      type C1 disease.
AB  - Niemann-Pick type C1 (NPC1) disease results from a defect in the NPC1 protein and
      is characterized by a pathological accumulation of cholesterol and glycolipids in
      endocytic organelles. We followed the biosynthesis and trafficking of NPC1 with
      the use of a functional green fluorescent protein-fused NPC1. Newly synthesized
      NPC1 is exported from the endoplasmic reticulum and requires transit through the
      Golgi before it is targeted to late endosomes. NPC1-containing late endosomes
      then move by a dynamic process involving tubulation and fission, followed by
      rapid retrograde and anterograde migration along microtubules. Cell fusion
      studies with normal and mutant NPC1 cells show that exchange of contents between
      late endosomes and lysosomes depends upon ongoing tubulovesicular late endocytic
      trafficking. In turn, rapid endosomal tubular movement requires an intact NPC1
      sterol-sensing domain and is retarded by an elevated endosomal cholesterol
      content. We conclude that the neuropathology and cellular lysosomal lipid
      accumulation in NPC1 disease results, at least in part, from striking defects in
      late endosomal tubulovesicular trafficking.

PMID- 11296290
TI  - Biomechanical activation of vascular endothelium as a determinant of its
      functional phenotype.
AB  - One of the striking features of vascular endothelium, the single-cell-thick
      lining of the cardiovascular system, is its phenotypic plasticity. Various
      pathophysiologic factors, such as cytokines, growth factors, hormones, and
      metabolic products, can modulate its functional phenotype in health and disease.
      In addition to these humoral stimuli, endothelial cells respond to their
      biomechanical environment, although the functional implications of this
      biomechanical paradigm of activation have not been fully explored. Here we
      describe a high-throughput genomic analysis of modulation of gene expression
      observed in cultured human endothelial cells exposed to two well defined
      biomechanical stimuli-a steady laminar shear stress and a turbulent shear stress
      of equivalent spatial and temporal average intensity. Comparison of the
      transcriptional activity of 11,397 unique genes revealed distinctive patterns of
      up- and down-regulation associated with each type of stimulus. Cluster analyses
      of transcriptional profiling data were coupled with other molecular and cell
      biological techniques to examine whether these global patterns of biomechanical
      activation are translated into distinct functional phenotypes. Confocal
      immunofluorescence microscopy of structural and contractile proteins revealed the
      formation of a complex apical cytoskeleton in response to laminar shear stress.
      Cell cycle analysis documented different effects of laminar and turbulent shear
      stresses on cell proliferation. Thus, endothelial cells have the capacity to
      discriminate among specific biomechanical forces and to translate these input
      stimuli into distinctive phenotypes. The demonstration that hemodynamically
      derived stimuli can be strong modulators of endothelial gene expression has
      important implications for our understanding of the mechanisms of vascular
      homeostasis and atherogenesis.

PMID- 11296291
TI  - Spatial and temporal emergence of high proliferative potential hematopoietic
      precursors during murine embryogenesis.
AB  - During mouse embryogenesis, two waves of hematopoietic progenitors originate in
      the yolk sac. The first wave consists of primitive erythroid progenitors that
      arise at embryonic day 7.0 (E7.0), whereas the second wave consists of definitive
      erythroid progenitors that arise at E8.25. To determine whether these unilineage
      hematopoietic progenitors arise from multipotential precursors, we investigated
      the kinetics of high proliferative potential colony-forming cells (HPP-CFC),
      multipotent precursors that give rise to macroscopic colonies when cultured in
      vitro. No HPP-CFC were found at presomite stages (E6.5-E7.5). Rather, HPP-CFC
      were detected first at early somite stages (E8.25), exclusively in the yolk sac.
      HPP-CFC were found subsequently in the bloodstream at higher levels than the
      remainder of the embryo proper. However, the yolk sac remains the predominant
      site of HPP-CFC expansion (>100-fold) until the liver begins to serve as the
      major hematopoietic organ at E11.5. On secondary replating, embryonic HPP-CFC
      give rise to definitive erythroid and macrophage (but not primitive erythroid)
      progenitors. Our findings support the hypothesis that definitive but not
      primitive hematopoietic progenitors originate from yolk sac-derived HPP-CFC
      during late gastrulation.

PMID- 11296292
TI  - Multiscale assessment of patterns of avian species richness.
AB  - The search for a common cause of species richness gradients has spawned more than
      100 explanatory hypotheses in just the past two decades. Despite recent
      conceptual advances, further refinement of the most plausible models has been
      stifled by the difficulty of compiling high-resolution databases at continental
      scales. We used a database of the geographic ranges of 2,869 species of birds
      breeding in South America (nearly a third of the world's living avian species) to
      explore the influence of climate, quadrat area, ecosystem diversity, and
      topography on species richness gradients at 10 spatial scales (quadrat area,
      approximately 12,300 to approximately 1,225,000 km(2)). Topography,
      precipitation, topography x latitude, ecosystem diversity, and cloud cover
      emerged as the most important predictors of regional variability of species
      richness in regression models incorporating 16 independent variables, although
      ranking of variables depended on spatial scale. Direct measures of ambient energy
      such as mean and maximum temperature were of ancillary importance. Species
      richness values for 1 degrees x 1 degrees latitude-longitude quadrats in the
      Andes (peaking at 845 species) were approximately 30-250% greater than those
      recorded at equivalent latitudes in the central Amazon basin. These findings
      reflect the extraordinary abundance of species associated with humid montane
      regions at equatorial latitudes and the importance of orography in avian
      speciation. In a broader context, our data reinforce the hypothesis that
      terrestrial species richness from the equator to the poles is ultimately governed
      by a synergism between climate and coarse-scale topographic heterogeneity.

PMID- 11296293
TI  - Correlation of breath ammonia with blood urea nitrogen and creatinine during
      hemodialysis.
AB  - We have spectroscopically determined breath ammonia levels in seven patients with
      end-stage renal disease while they were undergoing hemodialysis at the University
      of California, Los Angeles, dialysis center. We correlated these measurements
      against simultaneously taken blood samples that were analyzed for blood urea
      nitrogen (BUN) and creatinine, which are the accepted standards indicating the
      level of nitrogenous waste loading in a patient's bloodstream. Initial levels of
      breath ammonia, i.e., at the beginning of dialysis, are between 1,500 ppb and
      2,000 ppb (parts per billion). These levels drop very sharply in the first 15-30
      min as the dialysis proceeds. We found the reduction in breath ammonia
      concentration to be relatively slow from this point on to the end of dialysis
      treatment, at which point the levels tapered off at 150 to 200 ppb. For each
      breath ammonia measurement, taken at 15-30 min intervals during the dialysis, we
      also sampled the patient's blood for BUN and creatinine. The breath ammonia data
      were available in real time, whereas the BUN and creatinine data were available
      generally 24 h later from the laboratory. We found a good correlation between
      breath ammonia concentration and BUN and creatinine. For one of the patients, the
      correlation gave an R(2) of 0.95 for breath ammonia and BUN correlation and an
      R(2) of 0.83 for breath ammonia and creatinine correlation. These preliminary
      data indicate the possibility of using the real-time breath ammonia measurements
      for determining efficacy and endpoint of hemodialysis.

PMID- 11296294
TI  - Retroviral RNA identified in the cerebrospinal fluids and brains of individuals
      with schizophrenia.
AB  - Schizophrenia is a serious brain disease of uncertain etiology. A role for
      retroviruses in the etiopathogenesis of some cases of schizophrenia has been
      postulated on the basis of clinical and epidemiological observations. We found
      sequences homologous to retroviral pol genes in the cell-free cerebrospinal
      fluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or
      schizoaffective disorder. Retroviral sequences also were identified in the CSFs
      of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences
      were not identified in any of the CSFs obtained from 22 individuals with
      noninflammatory neurological diseases or from 30 individuals without evidence of
      neurological or psychiatric diseases (chi(2) = 19.25, P < 0.001). The nucleotide
      sequences identified in the CSFs of the individuals with schizophrenia or
      schizoaffective disorder were related to those of the human endogenous retroviral
      (HERV)-W family of endogenous retroviruses and to other retroviruses in the
      murine leukemia virus genus. Transcription of RNA homologous to members of the
      HERV-W family of retroviruses also was found to be up-regulated differentially in
      the frontal cortex regions of brains obtained postmortem from individuals with
      schizophrenia, as compared with corresponding tissue from individuals without
      psychiatric diseases. The transcriptional activation of certain retroviral
      elements within the central nervous system may be associated with the development
      of schizophrenia in at least some individuals. The further characterization of
      retroviral elements within the central nervous system of individuals with
      schizophrenia might lead to improved methods for the diagnosis and management of
      this disorder.

PMID- 11296295
TI  - Antisense-mediated depletion of p300 in human cells leads to premature G1 exit
      and up-regulation of c-MYC.
AB  - The cAMP-response element-binding protein (CREB)-binding protein and p300 are two
      highly conserved transcriptional coactivators and histone acetyltransferases that
      integrate signals from diverse signal transduction pathways in the nucleus and
      also link chromatin remodeling with transcription. In this report, we have
      examined the role of p300 in the control of the G(1) phase of the cell cycle in
      nontransformed immortalized human breast epithelial cells (MCF10A) and
      fibroblasts (MSU) by using adenovirus vectors expressing p300-specific antisense
      sequences. Quiescent MCF10A and MSU cells expressing p300-specific antisense
      sequences synthesized p300 at much reduced levels and exited G(1) phase without
      serum stimulation. These cells also showed an increase in cyclin A and cyclin A-
      and E-associated kinase activities characteristic of S phase induction. Further
      analysis of the p300-depleted quiescent MCF10A cells revealed a 5-fold induction
      of c-MYC and a 2-fold induction of c-JUN. A direct target of c-MYC, CAD, which is
      required for DNA synthesis, was also found to be up-regulated, indicating that up
      regulation of c-MYC functionally contributed to DNA synthesis. Furthermore, S
      phase induction in p300-depleted cells was reversed when antisense c-MYC was
      expressed in these cells, indicating that up-regulation of c-MYC may directly
      contribute to S phase induction. Adenovirus E1A also induced DNA synthesis and
      increased the levels of c-MYC and c-JUN in serum-starved MCF10A cells in a p300
      dependent manner. Our results suggest an important role of p300 in cell cycle
      regulation at G(1) and raise the possibility that p300 may negatively regulate
      early response genes, including c-MYC and c-JUN, thereby preventing DNA synthesis
      in quiescent cells.

PMID- 11296296
TI  - Complete genome sequence of an M1 strain of Streptococcus pyogenes.
AB  - The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram
      positive pathogen, has been determined and contains 1,752 predicted protein
      encoding genes. Approximately one-third of these genes have no identifiable
      function, with the remainder falling into previously characterized categories of
      known microbial function. Consistent with the observation that S. pyogenes is
      responsible for a wider variety of human disease than any other bacterial
      species, more than 40 putative virulence-associated genes have been identified.
      Additional genes have been identified that encode proteins likely associated with
      microbial "molecular mimicry" of host characteristics and involved in rheumatic
      fever or acute glomerulonephritis. The complete or partial sequence of four
      different bacteriophage genomes is also present, with each containing genes for
      one or more previously undiscovered superantigen-like proteins. These prophage
      associated genes encode at least six potential virulence factors, emphasizing the
      importance of bacteriophages in horizontal gene transfer and a possible mechanism
      for generating new strains with increased pathogenic potential.

PMID- 11296297
TI  - Epstein-Barr virus latent-infection membrane proteins are palmitoylated and raft
      associated: protein 1 binds to the cytoskeleton through TNF receptor cytoplasmic
      factors.
AB  - Epstein-Barr virus encodes integral membrane proteins LMP1 and LMP2A in
      transformed lymphoblastoid cell lines. We now find that LMP1 associates with the
      cell cytoskeleton through a tumor necrosis factor receptor-associated factor
      interacting domain, most likely mediated by tumor necrosis factor receptor
      associated factor 3. LMP1 is palmitoylated, and the transmembrane domains
      associate with lipid rafts. Mutation of LMP1 cysteine-78 abrogates palmitoylation
      but does not affect raft association or NF-kappaB or c-Jun N-terminal kinase
      activation. LMP2A also associates with rafts and is palmitoylated but does not
      associate with the cell cytoskeleton. The associations of LMP1 and LMP2A with
      rafts and of LMP1 with the cell cytoskeleton are likely to effect interactions
      with cell proteins involved in shape, motility, signal transduction, growth, and
      survival.

PMID- 11296298
TI  - Allosteric modulation of Ca2+ channels by G proteins, voltage-dependent
      facilitation, protein kinase C, and Ca(v)beta subunits.
AB  - N-type and P/Q-type Ca(2+) channels are inhibited by neurotransmitters acting
      through G protein-coupled receptors in a membrane-delimited pathway involving
      Gbetagamma subunits. Inhibition is caused by a shift from an easily activated
      "willing" (W) state to a more-difficult-to-activate "reluctant" (R) state. This
      inhibition can be reversed by strong depolarization, resulting in prepulse
      facilitation, or by protein kinase C (PKC) phosphorylation. Comparison of
      regulation of N-type Ca(2+) channels containing Cav2.2a alpha(1) subunits and P/Q
      type Ca(2+) channels containing Ca(v)2.1 alpha(1) subunits revealed substantial
      differences. In the absence of G protein modulation, Ca(v)2.1 channels containing
      Ca(v)beta subunits were tonically in the W state, whereas Ca(v)2.1 channels
      without beta subunits and Ca(v)2.2a channels with beta subunits were tonically in
      the R state. Both Ca(v)2.1 and Ca(v)2.2a channels could be shifted back toward
      the W state by strong depolarization or PKC phosphorylation. Our results show
      that the R state and its modulation by prepulse facilitation, PKC
      phosphorylation, and Ca(v)beta subunits are intrinsic properties of the Ca(2+)
      channel itself in the absence of G protein modulation. A common allosteric model
      of G protein modulation of Ca(2+)-channel activity incorporating an intrinsic
      equilibrium between the W and R states of the alpha(1) subunits and modulation of
      that equilibrium by G proteins, Ca(v)beta subunits, membrane depolarization, and
      phosphorylation by PKC accommodates our findings. Such regulation will modulate
      transmission at synapses that use N-type and P/Q-type Ca(2+) channels to initiate
      neurotransmitter release.

PMID- 11296299
TI  - Control of gating mode by a single amino acid residue in transmembrane segment
      IS3 of the N-type Ca2+ channel.
AB  - N-type Ca(2+) channels can be inhibited by neurotransmitter-induced release of G
      protein betagamma subunits. Two isoforms of Ca(v)2.2 alpha1 subunits of N-type
      calcium channels from rat brain (Ca(v)2.2a and Ca(v)2.2b; initially termed rbB-I
      and rbB-II) have different functional properties. Unmodulated Ca(v)2.2b channels
      are in an easily activated "willing" (W) state with fast activation kinetics and
      no prepulse facilitation. Activating G proteins shifts Ca(v)2.2b channels to a
      difficult to activate "reluctant" (R) state with slow activation kinetics; they
      can be returned to the W state by strong depolarization resulting in prepulse
      facilitation. This contrasts with Ca(v)2.2a channels, which are tonically in the
      R state and exhibit strong prepulse facilitation. Activating or inhibiting G
      proteins has no effect. Thus, the R state of Ca(v)2.2a and its reversal by
      prepulse facilitation are intrinsic to the channel and independent of G protein
      modulation. Mutating G177 in segment IS3 of Ca(v)2.2b to E as in Ca(v)2.2a
      converts Ca(v)2.2b tonically to the R state, insensitive to further G protein
      modulation. The converse substitution in Ca(v)2.2a, E177G, converts it to the W
      state and restores G protein modulation. We propose that negatively charged E177
      in IS3 interacts with a positive charge in the IS4 voltage sensor when the
      channel is closed and produces the R state of Ca(v)2.2a by a voltage sensor
      trapping mechanism. G protein betagamma subunits may produce reluctant channels
      by a similar molecular mechanism.

PMID- 11296300
TI  - Neurogenesis in dentate subgranular zone and rostral subventricular zone after
      focal cerebral ischemia in the rat.
AB  - Because neurogenesis persists in the adult mammalian brain and can be regulated
      by physiological and pathological events, we investigated its possible
      involvement in the brain's response to focal cerebral ischemia. Ischemia was
      induced by occlusion of the middle cerebral artery in the rat for 90 min, and
      proliferating cells were labeled with 5-bromo-2'-deoxyuridine-5'-monophosphate
      (BrdUrd) over 2-day periods before sacrificing animals 1, 2 or 3 weeks after
      ischemia. Ischemia increased the incorporation of BrdUrd into cells in two
      neuroproliferative regions-the subgranular zone of the dentate gyrus and the
      rostral subventricular zone. Both effects were bilateral, but that in the
      subgranular zone was more prominent on the ischemic side. Cells labeled with
      BrdUrd coexpressed the immature neuronal markers doublecortin and proliferating
      cell nuclear antigen but did not express the more mature cell markers NeuN and
      Hu, suggesting that they were nascent neurons. These results support a role for
      ischemia-induced neurogenesis in what may be adaptive processes that contribute
      to recovery after stroke.

PMID- 11296301
TI  - Genome-wide expression analysis reveals dysregulation of myelination-related
      genes in chronic schizophrenia.
AB  - Neuropathological and brain imaging studies suggest that schizophrenia may result
      from neurodevelopmental defects. Cytoarchitectural studies indicate cellular
      abnormalities suggestive of a disruption in neuronal connectivity in
      schizophrenia, particularly in the dorsolateral prefrontal cortex. Yet, the
      molecular mechanisms underlying these findings remain unclear. To identify
      molecular substrates associated with schizophrenia, DNA microarray analysis was
      used to assay gene expression levels in postmortem dorsolateral prefrontal cortex
      of schizophrenic and control patients. Genes determined to have altered
      expression levels in schizophrenics relative to controls are involved in a number
      of biological processes, including synaptic plasticity, neuronal development,
      neurotransmission, and signal transduction. Most notable was the differential
      expression of myelination-related genes suggesting a disruption in
      oligodendrocyte function in schizophrenia.

PMID- 11296302
TI  - The generation, migration, and differentiation of olfactory neurons in the adult
      primate brain.
AB  - In adult rodents, neural progenitor cells in the subependymal (SZ) zone of the
      lateral cerebral ventricle generate neuroblasts that migrate in chains via the
      rostral migratory stream (RMS) into the olfactory bulb (OB), where they
      differentiate into interneurons. However, the existence of this neurogenic
      migratory system in other mammals has remained unknown. Here, we report the
      presence of a homologue of the rodent SZ/RMS in the adult macaque monkey, a
      nonhuman Old World primate with a relatively smaller OB. Our results-obtained by
      using combined immunohistochemical detection of a marker for DNA replication (5
      bromodeoxyuridine) and several cell type-specific markers-indicate that dividing
      cells in the adult monkey SZ generate neuroblasts that undergo restricted chain
      migration over an extended distance of more than 2 cm to the OB and differentiate
      into granule interneurons. These findings in a nonhuman primate extend and
      support the use of the SZ/RMS as a model system for studying neural regenerative
      mechanisms in the human brain.

PMID- 11296308
TI  - Images of the mind.

PMID- 11296303
TI  - Regulation of neuroblast mitosis is determined by PACAP receptor isoform
      expression.
AB  - Although neurogenesis in the embryo proceeds in a region- or lineage-specific
      fashion coincident with neuropeptide expression, a regulatory role for G protein
      coupled receptors (GPCR) remains undefined. Pituitary adenylate cyclase
      activating polypeptide (PACAP) stimulates sympathetic neuroblast proliferation,
      whereas the peptide inhibits embryonic cortical precursor mitosis. Here, by using
      ectopic expression strategies, we show that the opposing mitogenic effects of
      PACAP are determined by expression of PACAP receptor splice isoforms and
      differential coupling to the phospholipase C (PLC) pathway, as opposed to
      differences in cellular context. In embryonic day 14 (E14) cortical precursors
      transfected with the hop receptor variant, but not cells transfected with the
      short variant, PACAP activates the PLC pathway, increasing intracellular calcium
      and eliciting translocation of protein kinase C. Ectopic expression of the hop
      variant in cortical neuroblasts transforms the antimitotic effect of PACAP into a
      promitogenic signal. Furthermore, PACAP promitogenic effects required PLC pathway
      function indicated by antagonist U-73122 studies in hop-transfected cortical
      cells and native sympathetic neuroblasts. These observations highlight the
      critical role of lineage-specific expression of GPCR variants in determining
      mitogenic signaling in neural precursors.

PMID- 11296304
TI  - Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in
      cellular models of Huntington's disease.
AB  - This investigation was pursued to test the use of intracellular antibodies
      (intrabodies) as a means of blocking the pathogenesis of Huntington's disease
      (HD). HD is characterized by abnormally elongated polyglutamine near the N
      terminus of the huntingtin protein, which induces pathological protein-protein
      interactions and aggregate formation by huntingtin or its exon 1-containing
      fragments. Selection from a large human phage display library yielded a single
      chain Fv (sFv) antibody specific for the 17 N-terminal residues of huntingtin,
      adjacent to the polyglutamine in HD exon 1. This anti-huntingtin sFv intrabody
      was tested in a cellular model of the disease in which huntingtin exon 1 had been
      fused to green fluorescent protein (GFP). Expression of expanded repeat HD-polyQ
      GFP in transfected cells shows perinuclear aggregation similar to human HD
      pathology, which worsens with increasing polyglutamine length; the number of
      aggregates in these transfected cells provided a quantifiable model of HD for
      this study. Coexpression of anti-huntingtin sFv intrabodies with the abnormal
      huntingtin-GFP fusion protein dramatically reduced the number of aggregates,
      compared with controls lacking the intrabody. Anti-huntingtin sFv fused with a
      nuclear localization signal retargeted huntingtin analogues to cell nuclei,
      providing further evidence of the anti-huntingtin sFv specificity and of its
      capacity to redirect the subcellular localization of exon 1. This study suggests
      that intrabody-mediated modulation of abnormal neuronal proteins may contribute
      to the treatment of neurodegenerative diseases such as HD, Alzheimer's,
      Parkinson's, prion disease, and the spinocerebellar ataxias.

PMID- 11296309
TI  - Brain-behavior relationships in obsessive-compulsive disorder.
AB  - Advances in neuroimaging have led to a greater understanding of brain-behavior
      relationships in obsessive-compulsive disorder (OCD). This article provides an
      updated review and analysis of the structural and functional neuroimaging studies
      in OCD published to date and discusses how evidence from various types of
      neuroimaging studies has been synthesized to generate and test hypotheses
      regarding these relationships. We also review the basic science literature on the
      functional neuroanatomy of cortico-basal ganglia-thalamo-cortical circuits and
      integrate this information with neuroimaging data in OCD, to present a
      theoretical model of brain mediation of OCD symptoms and response to treatment.
      Taken together, neuroimaging studies indicate that OCD symptoms are mediated by
      hyperactivity in orbitofrontal-subcortical circuits, which may be attributable to
      an imbalance of tone between direct and indirect striato-pallidal pathways.
      Serotonergic drugs may ameliorate OCD symptoms by changing the relative balance
      of tone through the indirect versus direct orbitofrontal-subcortical pathways,
      thereby decreasing activity in the overall circuit that exists in the symptomatic
      state.

PMID- 11296310
TI  - Prefrontal-subcortical and limbic circuit mediation of major depressive disorder.
AB  - Substantial progress has been made in elucidating the pathophysiology of major
      depressive disorder (MDD) using functional and structural brain imaging. In
      functional imaging studies comparing MDD subjects to normal controls at baseline,
      dorsolateral prefrontal cortex (DLPFC) activity has been found to be decreased
      and ventrolateral prefrontal cortex (VLPFC) activity has been found to be
      increased in MDD. Other regions found abnormal in baseline studies include the
      anterior cingulate gyrus (AC), temporal lobe, and basal ganglia. Studies
      examining mood state change (using sleep deprivation, sadness-induction, and
      tryptophan depletion) and changes from pre- to posttreatment have generally shown
      improvement of these abnormalities with improved MDD symptoms and worsening of
      these abnormalities with worsening symptoms. In structural imaging studies,
      decreased frontal lobe, hippocampal, and basal ganglia volumes are the most
      commonly reported findings. Several associations can be made between clinical
      features of MDD and brain function: (1) active sad thoughts/sadness with both
      decreased DLPFC and dorsal AC activity and increased VLPFC and ventral AC
      activity (2) psychomotor retardation with decreased left prefrontal activity (3)
      anxiety with increased left AC activity (4) impaired episodic memory with left
      prefrontal and medial temporal dysfunction and (5) impaired sustained attention
      with right prefrontal and parietal dysfunction.

PMID- 11296311
TI  - Prefrontal changes and treatment response prediction in depression.
AB  - A continuing challenge in the treatment of depression is how to determine whether
      an effective drug has been selected for a particular patient, given that
      individuals will respond to some antidepressants but not others. The factors that
      contribute to response for each person have been examined from a variety of
      perspectives, both psychological and physiological. Advances in neuroimaging and
      in quantitative electroencephalography (QEEG) have made it possible to examine
      features of brain activity that are associated with response. A new QEEG measure,
      cordance, is correlated with regional cortical perfusion, and has been used with
      retrospective and prospective studies to evaluate specific findings that are
      predictive of clinical response in major depression. We present here a series of
      depressed subjects treated with antidepressants of different classes; decreases
      in prefrontal activity were seen as early as 48 hours into treatment in
      responders and were absent in nonresponders. These findings suggest a role for
      the prefrontal region in mediating response to medications with different
      mechanisms of action and raise the possibility of using new QEEG measures to
      identify changes in brain activity that are predictive of clinical outcome from
      antidepressant treatment.

PMID- 11296312
TI  - Proton magnetic resonance spectroscopy (H-MRS) studies of schizophrenia.
AB  - Proton magnetic resonance spectroscopy ((1)H-MRS) is a noninvasive technique that
      can quantify biochemical compounds in the brain. (1)H-MRS has been used to
      investigate neural structures implicated in the pathology of schizophrenia. The
      majority of research has revealed reduced N-acetylaspartate (NAA), an index of
      neuronal integrity, in frontal and temporal regions of medicated and chronically
      ill patients with schizophrenia. This review summarizes basic principles of (1)H
      MRS, studies of frontal, temporal, subcortical, and cerebellar regions in
      schizophrenia. Technical and study design limitations are also discussed.

PMID- 11296313
TI  - Brain imaging in posttraumatic stress disorder.
AB  - This is a review article of neuroimaging studies in post-traumatic stress
      disorder (PTSD). Findings from structural, biochemical, and functional studies
      are summarized. Magnetic resonance imaging (MRI) volumetric studies have
      consistently reported decreased hippocampal volumes in PTSD. Proton magnetic
      resonance spectroscopy studies report decreased N-acetyl aspartate (NAA) ratios
      and absolute concentrations in the medial temporal lobe. Although still
      controversial, these findings from volumetric and spectroscopic studies are
      thought to represent decreased neuronal density of the hippocampus. Functional
      imaging studies document different patterns of limbic and paralimbic structure
      activation in PTSD compared with controls. Of theoretical importance are findings
      of failure to activate the anterior cingulate as well as amygdala activation
      during symptom provocation studies. Also, increased amygdala activation was found
      with a behavioral task targeted to this structure. A neurobiological model is
      presented that takes into account findings from neuroimaging studies in PTSD as
      well as animal studies of fear conditioning. This model proposes that central to
      symptom mediation is a dysfunction of the anterior cingulate, with a failure to
      inhibit amygdala activation and/or an intrinsic lower threshold of amygdala
      response to fearful stimuli. The model further proposes that hippocampal atrophy
      is a result of the chronic hyperarousal symptoms mediated by amygdala activation.

PMID- 11296314
TI  - Starving the brain: structural abnormalities and cognitive impairment in
      adolescents with anorexia nervosa.
AB  - Anorexia nervosa (AN) is one of the most common chronic illnesses afflicting
      adolescent girls and is associated severe medical complications. The structural
      abnormalities found in the brain of adolescents with AN are among the earliest
      and most striking physical consequences. In the past, it had been assumed that
      the brain abnormalities found in patients with AN reverse with weight-recovery.
      Recent evidence has shown that not all of these changes are completely reversible
      with weight recovery. To date, very little is known about the functional
      significance of these brain abnormalities. Several studies have shown that
      cognitive dysfunction is also a common feature of AN. Although current evidence
      suggests that there may be some degree of improvement in cognition with weight
      recovery, it is unclear whether cognition recovers fully or equally across all
      neuropsychological domains. Furthermore, it remains unknown whether the reported
      functional consequences are associated with these structural brain changes. This
      article will review the current literature on structural brain abnormalities and
      cognitive dysfunction in adolescents with AN.

PMID- 11296316
TI  - Prosthetic graft infection after descending thoracic/ thoracoabdominal aortic
      aneurysmectomy: management with in situ arterial allografts.
AB  - PURPOSE: Prosthetic graft infection is an uncommon but life-threatening
      complication of descending thoracic/thoracoabdominal aortic aneurysmectomy. The
      purpose of this study was to assess the value of in situ arterial allografts in
      the management of this complication. METHODS: From 1992 to 2000 we treated 11
      consecutive patients with prosthetic graft infection after descending
      thoracic/thoracoabdominal aortic aneurysmectomy by replacing the prosthetic graft
      with an in situ arterial allograft. There were 10 men and one woman with a mean
      age of 50.8 years (range, 32-73 years). The primary aortic disease was
      degenerative aneurysm in 6 patients, chronic type B dissection in 2 patients,
      inflammatory aneurysm in 1 patient, Marfan's disease in 1 patient, and Behcet's
      disease in 1 patient. Replacement involved only the descending thoracic aorta in
      three patients and more or less extensive segments of the thoracoabdominal aorta
      in eight patients. Signs of severe infection were present in all patients, and
      false anastomotic aneurysms were noted in six patients. Aortoenteric fistula
      occurred in three patients and aortobronchial fistula in two patients. The
      causative organisms were identified in nine patients. The mean interval between
      the primary surgery and reoperation was 33.4 +/- 27.5 months. Reoperation was
      performed under emergency conditions because of hemorrhage in three patients.
      Cardiopulmonary bypass with deep hypothermic circulatory arrest was used in seven
      patients. Allograft replacement of the aorta was associated with reimplantation
      of intercostal and/or visceral arteries in all patients. RESULTS: One patient
      died intraoperatively of heart failure during emergency surgery. Two patients
      died of persistent infection during the postoperative period at 19 and 58 days.
      Mean follow-up was 34 +/- 19 months. One patient died during the late follow-up
      period after surgery of the infrarenal aorta. Another patient underwent surgery
      for stenoses of one branch of a bifurcated allograft and a renal bypass graft to
      a solitary kidney. CONCLUSIONS: The use of in situ arterial allografts is a
      significant advance in the management of prosthetic graft infection after
      descending thoracic/thoracoabdominal aortic aneurysmectomy provided that
      reoperation is performed early.

PMID- 11296317
TI  - Developing the Vascular Quality of Life Questionnaire: a new disease-specific
      quality of life measure for use in lower limb ischemia.
AB  - AIMS: The purpose of this study was to develop and validate an easily used
      disease-specific quality of life (QOL) measure for patients with chronic lower
      limb ischemia and to design an evaluative instrument, responsive to within
      subject change, that adds to clinical measures of outcome when comparing
      treatment options in the management of lower limb ischemia. METHODS: The first
      phase consisted of item generation, item reduction, formulating, and pretesting
      in patients with ischemia. The proportion of patients who selected an item as
      troublesome and the mean importance they attached to it were combined to give a
      clinical impact factor. Items with the highest clinical impact factor were used
      to formulate a new 25-item questionnaire that was then pretested in 20 patients
      with lower limb ischemia. In the second phase, reliability, validity, and
      responsiveness of the new questionnaire were assessed in 39 patients with lower
      limb ischemia who were tested at 0 and 4 weeks. The King's College Hospital's
      Vascular Quality of Life Questionnaire and the Short-Form 36 were administered at
      each visit, and treadmill walking distance and ankle/brachial pressure indices
      were recorded. The new questionnaire's reliability, internal consistency,
      responsiveness, and validity were determined. RESULTS: Areas of QOL impairment
      were consistent through the ranges of disease severity and age, with no apparent
      differences between the men and women. Therefore, a single questionnaire is
      applicable to all patients with chronic lower limb ischemia. In stable patients
      test-retest scores demonstrated a reliability of r more than 0.90. Each item had
      internal consistency (item-domain Cronbach alpha =.7-.9). The questionnaire was
      responsive to change, with correlation between change in the questionnaire's
      total score and both global and clinical indicators of change (P <.001). The
      questionnaire showed face and construct validity. CONCLUSIONS: This disease
      specific questionnaire is reliable, responsive, valid, and ready for use as an
      outcome measure in clinical trials. It is sensitive to the concerns of patients
      with lower limb ischemia, offering a simple method to measure the effect of
      interventions on their QOL.

PMID- 11296318
TI  - The management of peripheral vascular complications associated with the use of
      percutaneous suture-mediated closure devices.
AB  - PURPOSE: The purpose of this study is to identify the peripheral vascular
      complications associated with the use of percutaneous suture-mediated closure
      (PSMC) devices and compare them with postcatheterization femoral artery
      complications not associated with PSMC devices. METHODS: This is a retrospective
      review of all patients admitted to the vascular surgery service at the
      Chattanooga Unit of the University of Tennessee Department of Surgery with a
      peripheral vascular complication after percutaneous femoral arteriotomy between
      July 1, 1998, and December 1, 1999. The complications followed the use of PSMC
      devices (group I, n = 11) and traditional compression therapy (group II, n = 14)
      to achieve arterial hemostasis. Group II was subdivided into patients who
      required operative intervention (group IIA, n = 8), and those who were treated
      without operation (group IIB, n = 6). RESULTS: No significant difference was
      found between groups I and II with regard to age (P =.227), time to vascular
      surgery consultation (P =.987), or diagnostic versus therapeutic catheterization
      (P =.897). A significant difference was found with regard to mean pseudoaneurysm
      size (group I = 5.9 cm, group II 2.9 cm; P =.003). Ultrasound compression was
      successfully performed in 66.6% of group II patients, but no (0.0%) patient in
      group I responded to this therapy (P =.016). Groups I and IIA had a significant
      difference for mean estimated blood loss (group I = 377.2 mL, group II = 121.8
      mL; P =.017) and requirement for transfusion (P =.013). More patients in group I
      required extensive surgical treatment (P =.007), with six of these patients
      requiring vein patch angioplasty during their treatment. More patients in group I
      also had infectious complications (n = 3) compared with group IIA (n = 1).
      CONCLUSION: In comparison with complications that follow percutaneous arteriotomy
      when PSMC devices are not used for hemostasis: (1) pseudoaneurysms after the use
      of PSMC devices are larger and do not respond to ultrasound compression, (2)
      complications associated with PSMC devices result in more blood loss and
      increased need for transfusion and are more likely to require extensive operative
      procedures, and (3) arterial infections after the use of PSMC devices are more
      common and require aggressive surgical management.

PMID- 11296319
TI  - Sequelae after limb-sparing surgery with major vascular resection for tumor of
      the lower extremity.
AB  - PURPOSE: Limb-sparing procedures have recently replaced amputations as the
      treatment for tumors invading major vessels of the lower extremity. Major
      arteries must be reconstructed for limb salvage. The veins are not usually
      reconstructed. This study was undertaken to investigate the sequelae such as
      chronic venous disease after venous resection for tumors. METHODS: Ten patients
      who underwent limb-sparing surgery for a tumor of the lower extremity or
      retroperitoneum that required major vascular resection were studied. The median
      follow-up period was 48 months. After combined resection of a major artery and
      vein, arterial reconstruction was performed. The veins were not reconstructed.
      The resected veins included the inferior vena cava (n = 2), the external iliac
      and common femoral veins (n = 3), the superficial femoral vein (n = 3), and the
      popliteal vein (n = 2). The main outcome measures were clinical classification of
      chronic venous disease in 10 patients and air plethysmography in seven patients.
      RESULTS: Clinical classification was C(0A) in 6 patients, C(3A) in 1 patient,
      C(3S) in 2 patients, and C(4S) in 1 patient. Venous claudication with
      uncontrollable edema was observed in two patients with C(3S) disease. Pain and
      itching with inflammatory skin changes were observed in one patient with C(4S)
      disease. These three patients had undergone resection of the femoral vein,
      including the deep femoral vein along with proximal adductor muscles. Air
      plethysmography revealed that the ejection fraction was significantly lower and
      the residual volume fraction was significantly higher in the three patients with
      symptoms than in symptom-free patients. CONCLUSIONS: Significant chronic venous
      disease was observed in the patients who underwent combined resection of the
      femoral vein, the deep femoral vein, and the adductor muscles for a tumor.

PMID- 11296320
TI  - Measurement of abdominal aortic aneurysms with three-dimensional ultrasound
      imaging: preliminary report.
AB  - OBJECTIVE: Accurate measurements of abdominal aortic aneurysms (AAAs) are
      required for surgical planning and monitoring over time. We have examined the
      feasibility of using a three-dimensional (3-D) ultrasound imaging system to
      derive quantitative measurements of interest from AAAs. METHODS: A normal aorta,
      a small AAA, and an AAA repaired with an endovascular stent graft were scanned
      with a 3-D ultrasound imaging system. For each case, a 3-D surface reconstruction
      was generated from manual outlines of a sequence of two-dimensional ultrasound
      images, registered in 3-D space with a magnetic tracking system. The surfaces
      were resampled in planes perpendicular to the vessel center axis to calculate
      cross-sectional area and maximum diameter as a function of distance along the
      length of the aorta. RESULTS: Cross-sectional area and maximum diameter were
      plotted along the length of the aneurysmal aortas from the renal arteries to the
      aortic bifurcation. The overall maximum diameter was found for both aneurysms.
      For the small AAA, the distances of the aneurysm from the renal arteries and the
      bifurcation were measured. For the repaired AAA, the location of the stent graft
      relative to the renal arteries was measured. CONCLUSIONS: 3-D surface
      reconstructions from ultrasound images show promise for quantitatively
      characterizing the geometry of AAAs both before surgery and after endovascular
      repair.

PMID- 11296321
TI  - The value of toe pulse waves in determination of risks for limb amputation and
      death in patients with peripheral arterial disease and skin ulcers or gangrene.
AB  - OBJECTIVES: The purpose of this study was to determine whether the presence of
      low amplitude of pulse waves recorded from the toes is related to the risk of
      subsequent amputation and death in patients with skin ulcers or gangrene and
      peripheral arterial disease, and how the risk of low wave amplitude relates to
      the risk associated with low peripheral pressures. METHODS: A total of 309
      patients with 346 limbs with skin lesions and arterial disease referred to the
      vascular laboratory were followed up for an average of 5 years (range, 1-8
      years). Measurements were carried out to obtain ankle and toe pressures, pressure
      indices, and toe pulse wave amplitude. These variables were related to the risks
      of major amputation and total and cardiovascular death by means of the Cox
      proportional hazards model. RESULTS: Low toe pulse wave amplitude (< or = 4 mm)
      was associated with increased risk of amputation (relative risks 4.20 in all
      limbs and 2.63 in those with toe pressure < or = 30 mm Hg; P <.01). Wave
      amplitude remained significantly associated with increased risk of amputation
      after controlling for each pressure variable (P <.01). Low pulse wave amplitude
      and toe/brachial index were associated with increased risks of both total and
      cardiovascular death in all patients (relative risks ranged from 1.43-1.73; P
      <.05) and in those with toe pressure of 30 mm Hg or less (relative risks 1.56
      1.90; P <.05). CONCLUSIONS: Low toe pulse wave amplitude is related significantly
      to increased risks of amputation and death in patients with skin lesions and
      arterial disease. The presence of low wave amplitude provides significant
      information in addition to peripheral pressures with respect to the risk of
      amputation.

PMID- 11296322
TI  - Air plethysmography: the answer in detecting past deep venous thrombosis.
AB  - PURPOSE: In this study we assessed the accuracy of air plethysmography (APG) as a
      means of detecting earlier deep venous thrombosis (DVT), in comparison with
      venography, to develop a preoperative test for patients with varicose veins.
      METHODS: In this retrospective analysis of prospectively acquired data, 202
      patients referred with the clinical suspicion of chronic venous obstruction (224
      lower limbs) and 41 patients (41 lower limbs) who had symptoms and signs
      suggestive of DVT, but had deep veins that appeared normal on venography, were
      studied with both venography and APG. RESULTS: The results of venography were
      negative for past DVT in 169 legs and confirmed past DVT in 96 limbs. The DVTs
      were confined to the calf in 19 limbs and were found at popliteal level, more
      proximal, or both in 77 limbs. A total of 95% of the limbs that had earlier
      proximal DVT (73 of 77) were identified by means of an APG outflow fraction with
      occlusion of the superficial veins in the first second (OFs) of less than 28%.
      This is analogous to the Q wave of the electrocardiogram, which is a means of
      denoting the presence of myocardial infarction. The specificity rate of the
      method in the detection of past proximal DVT was 96%, the positive predictive
      value was 92%, and the negative predictive value was 98%. CONCLUSION: APG is a
      practical, inexpensive, easy-to-perform, accurate, noninvasive method for the
      diagnosis of hemodynamically significant (ie, proximal or extensive calf DVT)
      chronic venous obstruction that could replace venography.

PMID- 11296323
TI  - Pressure measurements at rest and after heavy exercise to detect moderate
      arterial lesions in athletes.
AB  - PURPOSE: This study defined how ankle arterial blood pressure measurements should
      be analyzed for the detection of moderate arterial disease (asymptomatic while
      walking). We used external iliac artery endofibrosis as a unique model of an
      isolated moderate arterial lesion, the role of which in exercise-related pain can
      be surgically proven. METHODS: Patients who were ambulatory in our institutional
      referral center were studied. Brachial pressures, ankle pressures, and heart rate
      were measured simultaneously on all four limbs at rest and after maximal exercise
      in 108 healthy athletes and 78 patients (among 89 athletes referred for suspicion
      of endofibrosis) with confirmed or excluded external iliac endofibrosis. For
      these 78 patients, we calculated systolic ankle pressure change, ankle/brachial
      index, and deviation from the ankle/brachial index to heart rate regression line
      (DAHR) that was defined in the 108 healthy athletes. RESULTS: In patients with
      endofibrosis, ankle/brachial index and ankle pressure were normal at rest. One
      minute after exercise, areas (mean +/- SE of area) under the receiver operating
      characteristics curve for the diagnosis of endofibrosis were 0.91 +/- 0.02, 0.91
      +/- 0.03, 0.95 +/- 0.02, and 0.96 +/- 0.02 for ankle pressure, pressure change,
      ankle/brachial index, and DAHR, respectively. For all criteria, area decreased
      with time in the recovery period. CONCLUSION: After heavy-load exercise, the
      ankle/brachial index at minute 1 should be used rather than the systolic ankle
      pressure value or ankle pressure change as a means of improving the efficacy of
      the detection of endofibrosis in athletes. A 0.66 value of the index at minute 1
      after maximal exercise seems an optimal cutoff point for clinical use, providing
      a 90% sensitivity rate and 87% specificity rate in the diagnosis of moderate
      arterial lesions. At rest and after 1 minute of recovery, the ankle/brachial
      index to heart rate relationship should be considered to be an efficient tool for
      analyzing the results of pressures measurements and improving detection
      efficiency.

PMID- 11296324
TI  - Preprocedural risk stratification: identifying an appropriate population for
      carotid stenting.
AB  - PURPOSE: Given the uncertainties associated with carotid angioplasty and
      stenting, the initial assessment of the procedure may be best undertaken in a
      subgroup of patients at increased risk for complications with standard carotid
      surgery. In an effort to characterize such a subgroup, we reviewed the results of
      carotid endarterectomy in patients with and without significant medical
      comorbidity. METHODS: During a 10-year period 3061 carotid endarterectomies were
      performed at a single institution and entered prospectively into a registry. A
      high-risk patient subgroup was identified, defined by the presence of severe
      coronary artery disease, chronic obstructive lung disease, or renal
      insufficiency. The outcome of carotid endarterectomy was assessed with respect to
      perioperative stroke, myocardial infarction, or death, as well as the combined
      end point of one or more of the end points. RESULTS: The rate of the composite
      end point stroke/myocardial infarction/death was 3.8% in the total group of 3061
      patients who underwent endarterectomy. As individual end points, the rate of
      stroke was 2.1%, myocardial infarction 1.2%, and death 1.1%. Among the high-risk
      subset, the composite end point stroke/myocardial infarction/death occurred in
      7.4%. This rate was significantly greater than the corresponding rate of 2.9% in
      the low-risk subset (P <.0005). Similarly, the rate of stroke (3.5% vs 1.7%, P
      =.008) or death (4.4% vs 0.3%, P <.001) as solitary events was significantly
      greater in high-risk patients. CONCLUSIONS: Although carotid endarterectomy is an
      extremely safe procedure in most patients, results are not as favorable in a high
      risk subset with severe coronary, pulmonary, or renal disease. The initial
      clinical evaluation of carotid stenting might best be undertaken in such a high
      risk population, one that comprises patients for whom standard therapy is
      associated with a high rate of complications.

PMID- 11296325
TI  - Histopathologic analysis of endovascular stent grafts from patients with aortic
      aneurysms: Does healing occur?
AB  - BACKGROUND: Research with animal models has demonstrated tissue healing of
      endovascular grafts in both native arterial segments and in experimentally
      created arterial aneurysms. Fundamental to the successful clinical use of
      endovascular grafts for the treatment of aneurysmal disease is the creation of a
      permanent hemostatic seal between the graft ends and the arterial wall.
      Characteristics of this healing process in patients with aneurysmal disease have
      not been fully studied. In this study, we analyzed the macroscopic and
      histopathologic changes of the arterial wall after endovascular repair of aortic
      aneurysms. METHODS: Over a 7-year period, 313 patients were treated with
      endovascular grafts to exclude arterial aneurysms of the thoracic and abdominal
      aorta. Of these patients, 11 had their endovascular grafts recovered for
      analysis. Five graft specimens were recovered during subsequent open aortic
      surgery. Six grafts were recovered at autopsy after the death of the patient of
      causes unrelated to the patient's endovascular graft. All specimens were fixed in
      formalin. Histologic analysis included light microscopy with hematoxylin and
      eosin and trichrome stains. Well-preserved specimens were selected after light
      microscopic examination and postfixed in 3% buffered glutaraldehyde for electron
      microscopy. The aortas from autopsy specimens were removed en bloc and fixed in
      formalin; representative regions of each graft were sectioned for analysis.
      Adherence of the graft to the vessel wall was categorized as densely adherent or
      easily separated after graft explantation. Traction applied to the graft-aortic
      anastomosis was equal to traction generated by suspending a standardized 2-kg
      weight. Infrarenal graft specimens were obtained with supraceliac aortic
      clamping, longitudinal aortotomy, and graft sampling before endograft revision.
      RESULTS: In eight patients, endograft fixation was found to be firmly adherent to
      the arterial wall. A translucent film of fibrinous material was consistently seen
      across the entire luminal surface of the endograft. Light and electron microscopy
      failed to demonstrate an endothelial layer or organized pseudointima at the graft
      artery interface. CONCLUSION: Despite suggestive experimental data regarding
      endograft healing in animals, minimal graft incorporation was apparent in the
      stent grafts recovered in this study. A greater emphasis on the construction and
      mechanism of fixation of endograft attachment systems will be important for long
      term device function.

PMID- 11296326
TI  - Endoleaks following endovascular repair of abdominal aortic aneurysm: the
      predictive value of preoperative anatomic factors--a review of 100 cases.
AB  - OBJECTIVE: The failure to maintain a secure exclusion of aortic aneurysms with
      intraluminally placed grafts has been termed endoleak. We performed a
      retrospective review of our first 100 transluminally repaired abdominal aortic
      aneurysms (AAAs) in an effort to identify preoperative factors that could predict
      which patients would have endoleaks. METHODS: Between February 1993 and September
      1998, 100 infrarenal aneurysms were treated with tube (39), bifurcated (45), and
      aortoiliac grafts (16). Endoleaks (early and late) developed in 34 patients.
      Preoperative computed tomography scans and angiograms for all patients were
      individually inspected by a single reviewer. Aortic characteristics analyzed
      included number of patent lumbar arteries, presence of a patent inferior
      mesenteric artery (IMA), calcification and thrombus at proximal and distal
      attachment sites, proximal aortic angulation, and graft-vessel size discrepancy
      at proximal and distal attachment sites. The prevalence of the preoperative
      factors was compared among patients with and without endoleaks. RESULTS:
      Endoleaks developed in 44% of tube, 33% of bifurcated, and 47% of aortoiliac
      grafts (P =.51). Correlation between total number of patent lumbar arteries,
      presence of a patent IMA, and endoleaks was not significant (P =.44,.95).
      Calcification at either proximal or distal attachment site did not increase the
      risk of endoleaks (P =.50,.62). The presence of thrombus at the attachment site
      (proximally or distally) also failed to increase endoleak rates (P =.12,.78).
      Degree of proximal aortic angulation did not differ between groups (P =.39). Size
      discrepancies between graft and aorta or iliac vessels at proximal or distal
      sites did not significantly differ (P >.54, >.13). Subgroup analysis of endoleaks
      with different tube types also failed to demonstrate significant differences
      among the three graft types (P >.05). CONCLUSION: Endoleaks develop in a
      significant number of endovascularly repaired AAAs. We were unable to demonstrate
      a statistically significant association with anatomic characteristics thought to
      predispose to the development of endoleaks. We find no predictive value
      associated with these anatomic factors.

PMID- 11296327
TI  - Extra-anatomic arterial reconstruction with ligation of common iliac arteries and
      embolization of the aneurysm for the treatment of abdominal aortic aneurysms in
      high-risk patients.
AB  - PURPOSE: The mortality of an unrepaired abdominal aortic aneurysm (AAA) generally
      exceeds the mortality associated with surgical repair. However, as our longevity
      increases, more frequently we see patients whose risk of surgical repair
      approximates the risk of rupture. We present an extra-anatomic bypass graft with
      complete aneurysm exclusion by iliac ligation and coil embolization of the
      aneurysm as an alternative for these high-risk patients. METHODS: An extra
      anatomic bypass graft, followed by bilateral iliac artery ligation
      (retroperitoneal approach) and complete coil embolization of the AAA, was
      performed in eight patients (mean age, 77 years) found to be at prohibitive
      operative risk because of multiple comorbidities (American Society of
      Anesthesiologists class IV). Most patients (5 of 8) were symptomatic on
      presentation with a mean AAA diameter of 7 cm (range, 6.7-9.5 cm). We repair
      approximately 30 infrarenal aneurysms per year electively at our institution.
      RESULTS: All patients tolerated the surgical procedures. The average hospital
      stay was 8 days. All but two aneurysms demonstrated complete thrombosis by 48
      hours. After 48 months there was no incidence of graft thrombosis, peripheral
      ischemia, visceral ischemia or thrombus infection. There was one perioperative
      death from aspiration pneumonia. Seventy-five percent (6 of 8) of patients have
      survived at least 1 year without surgical complications. No patient has had a
      ruptured aneurysm. CONCLUSION: Combining an extra-anatomic bypass graft and
      complete exclusion of the AAA by ligation of the common iliac arteries and a coil
      embolization is an effective, less invasive treatment option for patients with
      AAA and prohibitive operative risk. We emphasize the need for complete
      embolization documented by decreased aneurysm size.

PMID- 11296328
TI  - Prognosis of patients turned down for conventional abdominal aortic aneurysm
      repair in the endovascular and sonographic era: Szilagyi revisited?
AB  - PURPOSE: The United Kingdom Small Aneurysm study has demonstrated the low risk of
      rupture in aneurysms less than 5.5 cm in diameter. With the advent of endoluminal
      techniques, patients considered unfit to undergo laparotomy are now considered
      for endovascular repair. However, the natural history of aneurysms larger than
      5.5 cm remains uncertain, especially when severe comorbidity is present. In our
      center, we prospectively maintain records of all patients for whom elective
      aneurysm surgery was refused. This study documented the outcome of all patients
      referred with abdominal aortic aneurysms (AAAs) larger than 5.5 cm in diameter
      who were turned down for elective open repair and determined the cause of death
      and risk of rupture in all patients. METHODS: Details of all patients with AAAs
      from January 5, 1989, to January 5, 1999, were recorded, and demographic details
      on all patients with AAAs larger than 5.5 cm were collected. Copies of death
      certificates were obtained from the Office of National Statistics, local in
      hospital patient records, and general practitioner records. Results of postmortem
      examinations were also obtained. Aneurysms were stratified according to their
      size at presentation (5.5-5.9 cm, 6.0-7.0 cm, and > 7.0 cm), and the reasons no
      intervention was made were documented. RESULTS: A total of 106 patients were
      turned down for elective aneurysm surgery in the 10-year period (10.6 per year).
      The mean age of the patients was 78.4 years (SD, 7.4), and 70 were men and 36
      were women. At the end of the study, 76 patients (71.7%) had died. Overall, the 3
      year survival rate was 17%. Patients with AAAs larger than 7.0 cm lived a median
      of 9 months. A ruptured aneurysm was certified as a cause of death in 36% of the
      patients with an AAA of 5.5 to 5.9 cm, in 50% of the patients with an AAA of 6 to
      7.0 cm, and 55% of the patients with an AAA larger than 7.0 cm. Reasons given for
      not intervening were patient refusal (31 cases), the patient being "unfit for
      surgery" (18 cases), the "advanced age" of the patient (18 cases), cardiac
      disease (9 cases), cancer (9 cases), respiratory disease (6 cases), and other (15
      cases). CONCLUSION: Although we recognize the problems with death certification,
      we found that rupture was a significant cause of death in patients with an
      untreated AAA that was larger than 5.5 cm. Although little difference in outcome
      was observed in aneurysms in the 5.5 to 7.0 cm size range, patients with an AAA
      that was larger than 7.0 cm seemed to have a much poorer prognosis.

PMID- 11296329
TI  - A randomized study to evaluate the effect of a perioperative infusion of
      dopexamine on colonic mucosal ischemia after aortic surgery.
AB  - PURPOSE: Colonic ischemia after aortic surgery is associated with increased
      mortality and morbidity rates. This study was conducted as a single-center side
      arm to a multicenter, randomized, placebo-controlled study to evaluate the effect
      of dopexamine hydrochloride on its incidence. METHODS: Thirty patients, mean age
      65.1 years (range, 46-84), undergoing elective infrarenal aortic surgery were
      entered. Preoperative hemodynamic and respiratory parameters were optimized.
      Patients were then randomly assigned to receive a perioperative infusion of
      dopexamine at 2 microg/kg per minute (n = 12) or 0.9% saline placebo (n = 18).
      All patients underwent colonoscopy and biopsy preoperatively and 1 week
      postoperatively. Specimens were assessed for evidence of mucosal ischemia,
      presence of mast cell tryptase, myeloperoxidase activity, and both the inducible
      and endothelial isoforms of nitric oxide synthase. RESULTS: There was no
      significant difference in perioperative fluid and blood requirements or
      hemodynamic and respiratory parameters between the two groups. However, there was
      significantly less evidence of mucosal ischemic changes in dopexamine-treated
      patients (n = 1) compared with placebo (n = 8) (P =.049). Furthermore, when
      preoperative biopsies were compared with those performed 1 week postoperatively,
      nine (50%) patients in the placebo group and two (16.7%) in the dopexamine group
      scored worse. Although there was no significant difference in inflammatory
      markers between the two groups, both mast cell tryptase and myeloperoxidase
      expression were increased in patients with histologic evidence of ischemia (P
      <.05). Furthermore, inducible nitric oxide synthase staining within the vascular
      (P =.001) and lamina propria (P <.05) components of the mucosa was also
      significantly greater. CONCLUSION: A perioperative dopexamine infusion affords
      significant histologic protection to colonic mucosa after aortic surgery.

PMID- 11296330
TI  - New experiences with absolute ethanol sclerotherapy in the management of a
      complex form of congenital venous malformation.
AB  - BACKGROUND: Complex forms of congenital venous malformation have defied proper
      classification and confounded therapy. Through a newly designed multidisciplinary
      approach, these venous defects were properly diagnosed and classified according
      to the Hamburg classification. Absolute ethanol was adopted as a new scleroagent
      for this complex form of venous defects to improve overall treatment results with
      acceptable morbidity and recurrence rates. PATIENTS AND METHODS: Among 318
      patients aged 2 months to 60 years (130 men: mean age, 24.6 years; 188 women:
      mean age, 24.5 years), 143 patients were confirmed as having venous defects
      predominantly (45%). We conducted diagnostic evaluation with magnetic resonance
      imaging, whole body blood pool scan, duplex scans, transarterial microalbumin
      lung scans, air plethysmography, bone x-ray film, and angiography. Thirty of 143
      patients were indicated for the absolute ethanol sclerotherapy for the complex
      form of venous defects, and they completed 98 sessions of multistage therapy with
      direct puncture technique. Follow-up assessment (minimum, 6 months; average, 10.2
      months) was made as early results after completion of therapy. RESULTS: The
      immediate success rate at the completion of treatment through 98 sessions on 30
      patients was 92% (90/98). The reason for the failure of 8% (8/98 sessions) was
      mainly due to the lesion's inaccessibility to the nidus to deliver the alcohol
      safely. On follow-up assessment available on 28 of 30 patients, overall
      improvement of the lesions with good to fair response on clinical assessment was
      obtained in 27 (96%) of 28 patients. Similar good to fair responses were obtained
      on whole body blood pool scan assessment (14 [93%] of 15 patients) and also on
      magnetic resonance imaging assessment (12 [93%] of 13 patients). Various major to
      minor acute complications developed during the procedure in eight (26.7%) of 30
      patients through 16 (16.3%) of 98 sessions of the therapy: ischemic bullae,
      tissue fibrosis, deep venous thrombosis, pulmonary embolism, peripheral nerve
      palsy, and temporary pulmonary hypertension. All 24 incidences of complication
      were successfully managed with full recovery except one case of permanent
      peroneal nerve palsy that was present during 18 months of follow-up. No single
      recurrence has been detected to date. CONCLUSION: Absolute ethanol sclerotherapy
      alone can deliver excellent results in complex forms of venous malformations with
      considerable but acceptable morbidity and may be able to reduce the morbidity
      involved with the conventional surgical therapy alone on complex forms of venous
      malformation. No recurrence or deterioration of the therapy results was observed
      during the follow-up period (average, 10.2 months) after the completion of
      multistaged therapy.

PMID- 11296331
TI  - In situ hemodynamics of perforating veins in chronic venous insufficiency.
AB  - PURPOSE: The prevalence of incompetent perforators increases linearly with the
      clinical severity of chronic venous insufficiency (CVI) and the presence of deep
      vein incompetence. Putative transmission of deep vein pressure to skin may cause
      dermal hypoxia and ulceration. Despite extensive prospective interest in the
      contribution of perforators toward CVI, their hemodynamic role remains
      controversial. The aim of this prospective study was to determine the in situ
      hemodynamic performance of incompetent perforating veins across the clinical
      spectrum of CVI, by means of duplex ultrasonography. METHODS: A total of 265
      perforating veins of 90 legs that had clinical signs and symptoms consistent with
      CVI in 67 patients referred consecutively to the blood flow laboratory were
      studied. The clinical distribution of the examined limbs was CEAP(0), 10 limbs;
      CEAP(1-2), 39 limbs; CEAP(3-4), 21 limbs; and CEAP(5-6), 20 limbs. With the use
      of gated-Doppler ultrasonography on real-time B-mode imaging, the flow velocity
      waveforms were obtained from the lumen of perforators on release of manual distal
      leg compression in the sitting position and analyzed for peak and mean
      velocities, time to peak velocity, volume flow, venous volume displaced outward,
      and flow pulsatility. The diameter and duration of outward flow (abnormal reflux
      > 0.5 seconds) were also measured. RESULTS: Incompetent perforators had bigger
      diameters, higher peak and mean velocities and volume flow, longer time to peak
      velocity, and bigger venous volume displaced outward (VV(outward)) than competent
      perforators (all, P <.0001). The diameter of incompetent perforators did not
      change significantly with CEAP class (all, P >.1). Incompetent thigh and lower
      third calf perforators had a significantly bigger diameter than perforators in
      the upper and middle calf combined (both, P <.05), in incompetent perforators:
      reflux duration was unaffected by CEAP class or site (P >.3); peak velocity was
      higher in those in CEAP(3-4) than those in CEAP(1-2) (P =.024); mean velocity in
      those in CEAP(3-6) during the first second of reflux was twice that of those in
      CEAP(1-2) (P <.0001); both higher volume flow and VV(outward) were found in the
      thigh perforators than those in the upper and middle calf thirds (P <.03); CEAP(3
      6) volume flow and VV(outward), both in the first second, were twice that in
      those in CEAP(1-2) (P <.002); flow pulsatility in those in CEAP(5-6) was lower
      than in those in CEAP(1-2) (P =.014); in deep vein incompetence, higher peak
      velocity, volume flow, VV(outward), and diameter occurred than in its absence (P
      <.01). CEAP designation correlated significantly with mean velocity and flow
      pulsatility, both in the first second (r = 0.3, P <.01). The flow direction
      pattern in perforator incompetence was uniform across the CVI spectrum: inward on
      distal manual limb compression, and outward on its release; competent perforators
      had a smaller percentage of outward flow on limb compression (P <.01).
      CONCLUSION: In addition to an increase in diameter, perforator incompetence is
      characterized by significantly higher mean and peak flow velocities, volume flow,
      and venous volume displaced outward, and a lower flow pulsatility. Differences in
      early reflux enable a better hemodynamic stratification of incompetent
      perforators in CVI classes. In the presence of deep reflux, incompetent
      perforators sustain further hemodynamic impairment. In situ hemodynamics enable
      quantification of the function of perforators and can be used in the
      identification of the clinically relevant perforators and the impact of surgery.

PMID- 11296332
TI  - Outcome after thrombolysis and selective thoracic outlet decompression for
      primary axillary vein thrombosis.
AB  - PURPOSE: Treatment for primary subclavian-axillary vein thrombosis (SAVT) at our
      institution consists of thrombolysis and anticoagulation for 3 months. Thoracic
      outlet decompression has been performed for a small number of patients. We wanted
      to review the functional outcomes of patients treated in such a manner. MATERIAL
      AND METHODS: The records of all patients treated for a first episode of SAVT at
      our hospital over the past 10 years were reviewed. Demographics, comorbidities,
      method of diagnosis, and treatment for SAVT were recorded. Long-term follow-up
      was obtained by chart review and asking patients to complete the DASH
      (disabilities of the arm, shoulder and hand) questionnaire that was developed by
      the American Academy of Orthopedic Surgeons. RESULTS: Twenty-eight patients, 20
      men and eight women, with a mean age of 36 were treated during the study period.
      The median time between onset of symptoms and treatment was 5.5 (range, 1-100)
      days. All patients had confirmation of the diagnosis by venography. Twenty-five
      patients received thrombolytic treatment with catheter-directed infusions of
      urokinase; in the other three patients the vein was chronically occluded. Twelve
      patients had some degree of residual stenosis and were treated with percutaneous
      transluminal angioplasty after thrombolysis. During the study period two patients
      underwent decompressive surgery. Twenty-one patients responded to the DASH
      questionnaire a mean of 2.9 years (range, 2 months to 8 years) after the episode
      of SAVT. Six (28%) of 21 patients were completely symptom free, 13 patients (62%)
      had DASH scores consistent with mild symptoms, and two patients had more severe
      symptoms. Twenty percent (4 of 21) of patients report some difficulty with work.
      CONCLUSIONS: Thrombolysis, followed by selective thoracic outlet decompression on
      the basis of the severity of patients' symptoms can be used as a therapeutic
      approach to SAVT without undue morbidity. The DASH questionnaire is a useful tool
      to evaluate results after therapy for SAVT.

PMID- 11296333
TI  - Renal cell carcinoma with extension of tumor thrombus into the vena cava:
      surgical strategy and prognosis.
AB  - PURPOSE: The outcome of patients who underwent radical resection of renal cell
      carcinoma extending into the vena cava was retrospectively analyzed, and risk
      factors for long-term survival were investigated. METHODS: From 1983 to 1999, 33
      patients who had renal cell carcinoma with inferior vena caval tumor extension
      underwent 34 surgical procedures. There were 27 men and six women with an average
      age of 60.1 years. Twenty-two cases (64.7%) were classified as stage III (T1-2 N1
      M0 or T3 N0-1 M0), and 12 cases (35.3%) as stage IV (T4 or N2-3 or M1).
      Coexistent lung metastasis was found in seven cases (20.6%). The tumor thrombi
      invaded into the inferior vena cava below the hepatic hilum in 19 cases, below
      the orifice of hepatic veins in 12, and above the diaphragm in 3. Cardiopulmonary
      bypass graft was applied in 13 cases (38.2%). Inferior vena cava was
      reconstructed by direct suture (n = 19), polytetrafluoroethylene patch
      angioplasty (n = 13), or graft replacement (n = 2). RESULTS: Two patients died
      during the early postoperative period because of retrohepatic caval injury and
      intraoperative pulmonary embolism. Late death occurred in 16 patients; the causes
      of death were tumor recurrence in 15 and acute pulmonary embolism as a result of
      graft thrombosis in 1. Overall 1-, 5-, and 10-year survival rates were 70%, 44%,
      and 26.4%, respectively. One- and 5-year survival rates were 81.3% and 52.9% for
      stage III and 50% and 31.2% for stage IV; a statistically significant correlation
      was found between surgical staging and survival (P =.049). Patients without lymph
      node metastasis had a significant survival advantage over those with lymph node
      metastasis (P =.022). There was no significant difference in survival on the
      basis of the presence or absence of synchronous lung metastasis (P =.291). The
      degree of local extension of the tumor or the level of tumor thrombus did not
      tend to influence survival. CONCLUSIONS: Surgical prognosis in patients with
      renal cell carcinoma extending into the vena cava was determined by the staging
      of the tumor, especially lymph node status, and not by the level of tumor
      thrombus or the presence of concurrent lung metastasis. The use of
      cardiopulmonary bypass graft is recommended for the resection of tumor thrombus
      extending over the diaphragm.

PMID- 11296334
TI  - Extra-anatomic bypass graft for management of axillary artery occlusion in
      pitchers.
AB  - OBJECTIVE: Our goal was to evaluate the long-term results of vein bypass grafts
      for axillary artery occlusion, specifically those placed extra-anatomically to
      prevent arterial injury in pitchers. METHODS: With the greater saphenous veins
      used as the selected conduit, arterial bypass grafts were routed anterior to the
      pectoralis minor muscle in four baseball pitchers who had occlusion of the
      axillary artery. We performed a follow-up in excess of 10 years with evaluations
      of the bypass grafts by ultrasonic duplex scan and magnetic resonance
      angiography. RESULTS: All four pitchers treated in this manner returned to the
      game and played for several seasons without a recurrence of the arterial injury.
      Long-term evaluation of the bypass grafts did not reveal any structural or
      functional disorder. CONCLUSIONS: Axillary artery occlusion in an athlete can be
      effectively treated with a vein bypass graft placed extra-anatomically, anterior
      to the pectoralis minor muscle. The greater saphenous vein should be considered
      the conduit of choice.

PMID- 11296335
TI  - Brachial artery reconstruction for occlusive disease: a 12-year experience.
AB  - OBJECTIVE: Symptomatic arterial disease of the upper extremity is an uncommon
      problem. In this study, we evaluate our results with brachial artery
      reconstruction in patients who present with symptomatic atherosclerotic occlusive
      disease and compare this cohort's demographics with a similar group with lower
      extremity ischemia. METHODS: From 1986 to 1998, all patients presenting for upper
      extremity revascularization with chronic ischemia were prospectively entered into
      a vascular registry. Demographics, indications, outcomes, and patency were
      recorded. Patients presenting with embolus, pseudoaneurysm, or trauma were
      excluded. The Fisher exact and Student t tests were used to assess significance.
      RESULTS: Fifty-one (83%) bypass grafts were performed with autogenous conduit and
      the remainder with polytetrafluoroethylene. Indications included 18 (30%)
      patients with exertional arm pain, 35 (57%) with rest pain, and 8 (13%) with
      tissue loss. Twenty-five (45%) patients were male, 8 (14%) had diabetes, and 30
      (54%) were smokers. The mean age was 58 years (range, 33-93). The operative
      mortality rate was 1.8%, and follow-up ranged from 1 to 140 months. Eight
      occlusions were identified, with six occurring early. Five of these were in women
      with a smoking history. Only one of the 26 reconstructions that did not cross a
      joint occluded, whereas bypass grafts that did cross a joint occluded more
      frequently. No other major complications were recognized. CONCLUSION: Arm
      revascularization for ischemia can be performed with reasonable mortality and
      morbidity rates. These patients may represent a different subgroup of
      atherosclerotic disease than those with lower extremity involvement: they are
      more commonly women and smokers and less likely to be diabetic.

PMID- 11296336
TI  - Visceral artery aneurysm rupture.
AB  - PURPOSE: Aneurysms of the visceral arteries are infrequently encountered. Many
      are found incidentally and are thought to have a benign outcome. To better
      characterize these lesions and their clinical course, we reviewed our experience
      with visceral artery aneurysms (VAAs) at a single institution. METHODS: A
      retrospective analysis of all VAAs diagnosed at our institution over the past 10
      years was performed. The presentation, management, and outcome of therapy was
      examined for each patient. RESULTS: Thirty-four VAAs in 26 patients were
      diagnosed over the past 10 years. Four patients had multiple VAAs: splenic (17),
      hepatic (7), celiac (3), superior mesenteric (2), gastroduodenal (2),
      pancreaticoduodenal (1), right gastric (1), ileal (1) artery aneurysms.
      Associated aneurysms were found in 31% of patients and involved the thoracic
      aorta (3 patients), abdominal aorta (4 patients), renal arteries (2 patients),
      iliac artery (3 patients), lower extremity (1 patient), and intracranium (1
      patient). In 15 patients (58%), VAAs were detected before rupture by chance or
      because abdominal symptoms resulted in diagnostic evaluation. Eight of these
      underwent elective surgery, and there were no deaths. Of those 15 patients with
      known VAAs, one patient died of rupture and hemorrhage from an untreated splenic
      artery aneurysm. Eleven patients (42%) presented unexpectedly with rupture, and
      two died despite prompt surgical treatment. The mortality rate in patients who
      had ruptured VAAs was 25%, including those who presented with ruptured aneurysms
      and those observed whose aneurysms eventually ruptured. CONCLUSIONS: Aneurysms of
      the visceral arteries are rare but important vascular lesions. Associated
      aneurysms are common. Because of the risk of rupture, often with a fatal outcome,
      an aggressive approach to the treatment of VAA is essential.

PMID- 11296337
TI  - A comparison of para-anastomotic compliance profiles after vascular anastomosis:
      nonpenetrating clips versus standard sutures.
AB  - PURPOSE: Anastomotic compliance is an important predictive factor for long-term
      patency of small diameter vascular reconstruction. In this experimental study we
      compare the compliance of continuous and interrupted sutured vascular anastomoses
      with those using nonpenetrating clips. METHODS: Both common carotid arteries in
      nine goats (average weight, 57 +/- 5.7 kg) were transected, and end-to-end
      anastomoses were constructed with nonpenetrating clips or polypropylene sutures.
      The latter were applied with both interrupted and continuous techniques.
      Intraluminal pressure was measured with a Millar Mikro-tip transducer, and vessel
      wall motion was determined with duplex ultrasound equipped with an echo-locked
      wall-tracking system. Diametrical compliance was determined. Environmental
      scanning electron microscopy was performed on explanted anastomoses. RESULTS:
      There was a reduction in anastomotic compliance and associated proximal and
      distal para-anastomotic hypercompliant zones with the use of all techniques.
      However, compliance loss was significantly less in those anastomoses with clips
      and interrupted sutures when compared with continuous suture (P <.001).
      Furthermore, the total compliance mismatch across anastomoses with continuous
      sutures was significantly greater than those with clips or interrupted sutures (P
      <.05). The mean time for constructing clipped anastomoses was 5.7 +/- 1.4
      minutes, which was significantly less than either continuous (P <.0001) or
      interrupted sutures (P <.0001). Furthermore, environmental scanning electron
      microscopy demonstrated minimal intimal damage with good intimal apposition in
      the clip group. CONCLUSION: Anastomoses performed with nonpenetrating clips
      resulted in improved para-anastomotic compliance profiles and reduced intimal
      damage when compared with those with polypropylene sutures. These benefits may
      enhance long-term graft patency by reducing the risk of anastomotic intimal
      hyperplasia.

PMID- 11296338
TI  - Enhancement of neointima formation with tissue-type plasminogen activator.
AB  - PURPOSE: Indirect evidence suggests that tissue plasminogen activator (tPA)
      either limits or does not alter restenosis. However, tPA enhances tumor
      invasiveness through matrix remodeling, and several elements of degraded matrix
      enhance smooth muscle cell mitogenesis. We use either local adenoviral-mediated
      overexpression of tPA or systemic infusion of recombinant tPA combined with
      mechanical overdilation of rabbit common femoral arteries to evaluate the impact
      of tPA on neointima formation. METHODS: Left common femoral arteries of New
      Zealand white rabbits were transfected in situ either with an adenoviral
      construct-expressing tPA or a viral control (adenoviral-construct-expressing beta
      galactosidase) or nonviral (buffer) control after balloon angioplasty injury. At
      7 and 28 days, left common femoral artery segments were harvested (n = 4 for each
      group and time point). Vessel segments were examined for intimato-media ratio,
      smooth muscle cell proliferation, extracellular matrix, and inflammatory
      response. Thrombus formation was evaluated after 3 days (n = 3 for each group).
      In a second experiment, New Zealand white rabbits (n = 3 per group, per time
      point) underwent mechanical dilation followed by buffer treatment or systemic tPA
      infusion according to a widely clinically used accelerated infusion protocol.
      Treated artery segments were harvested after 7 or 28 days and processed for
      intima-to-media ratio determination and class-wide histochemical determination of
      collagenous extracellular matrix and collagen content. RESULTS: Both rate and
      degree of neointima formation increase dramatically with overexpression (250%
      461% relative to controls at 7 and 28 days). Substantial early matrix degradation
      is observed in vessels treated with local overexpression of tPA, although no
      increases in local inflammation or in smooth muscle proliferation occur. Late
      enhancement of smooth muscle proliferation emerges, consistent with secondary
      impact of perturbed matrix components. Systemic infusion of tPA according to
      clinical protocols also results in early and late enhancement of neointima
      formation in this model (34%-52% relative to controls at at 7 and 28 days), with
      significant early collagenous matrix degradation. Systemic infusion, although
      significant, did not attain the degree of neointima formation present with
      overexpression. CONCLUSION: With some evidence of dose-dependence, tissue
      plasminogen activator enhances neointima formation after angioplasty in a rabbit
      model. Early matrix degradation precedes change in rates of proliferation and
      underlies this effect in spite of several antirestenotic actions including
      decreased thrombus and decreased macrophage recruitment in this model.

PMID- 11296339
TI  - Effects of dietary L-arginine on structure and function of flow-restricted vein
      grafts.
AB  - PURPOSE: Experiments were designed to determine effects of dietary
      supplementation with L -arginine on structure and function of flow-restricted
      vein grafts. METHODS: Saphenous veins were placed as bilateral interposition
      grafts in femoral arteries of two groups of adult male mongrel dogs; one group
      was maintained on a normal diet (control), the other group supplemented with L 
      arginine (200 mg/kg per day) beginning 1 week before surgery. In each dog, flow
      was reduced by 50% in one graft by placing an adjustable clamp on the artery
      distal to the distal anastomosis. Plasma amino acids and oxidized products of
      nitric oxide (NO(x )) were measured before and after L -arginine feeding. At
      postoperative week 4, grafts were removed and prepared for organ chamber studies
      to determine functions of the endothelium or smooth muscle and for histology.
      RESULTS: Plasma L -arginine increased within 3 hours after feeding and increased
      from 141 +/- 8 nmol/mL to 169 +/- 11 nmol/mL (n = 6) after 5 weeks of
      supplementation. Plasma ornithine and citrulline paralleled arginine, whereas
      circulating NO(x ) was unchanged. Maximal contractions to 60 mmol/L KCl were
      reduced in grafts from L -arginine-fed dogs. Endothelium-dependent relaxations to
      the calcium ionophore A23187 and relaxations of the smooth muscle NO were reduced
      in grafts from L -arginine-fed dogs. Neointimal hyperplasia was increased in
      grafts with reduced flow and not affected by arginine feeding. CONCLUSIONS:
      Dietary supplementation with L -arginine did not increase plasma NO in dogs with
      peripheral vein grafts or increase endothelium-dependent relaxations in control
      or flow-restricted grafts. Therefore, dietary supplementation with L -arginine
      may not improve long-term functions of flow-restricted peripheral bypass grafts.

PMID- 11296340
TI  - Recombinant bactericidal/permeability-increasing protein attenuates the systemic
      inflammatory response syndrome in lower limb ischemia-reperfusion injury.
AB  - OBJECTIVES: Hind limb ischemia-reperfusion (I/R) injury increases gut
      permeability, and resultant endotoxemia is associated with an amplified systemic
      inflammatory response syndrome leading to multiple organ dysfunction syndrome. We
      studied the potential role of recombinant bactericidal/permeability-increasing
      protein (rBPI(21) ), a novel antiendotoxin therapy, in modulating endotoxin
      enhanced systemic inflammatory response syndrome in hind limb I/R injury.
      METHODS: In this prospective, randomized, controlled, experimental animal study,
      48 male Wistar rats, weighing 300 to 350 g, were randomized to a control group
      (sham) and five groups undergoing 3 hours bilateral hind limb ischemia with 2
      hours reperfusion (I/R) (n = 8 per group). The control and untreated I/R groups
      received thaumatin, a control-protein preparation, at 2 mg/kg. Treatment groups
      were administered rBPI(21) intravenously at 1, 2, or 4 mg/kg body weight at the
      beginning of reperfusion; an additional group was administered rBPI(21)
      intravenously at 2 mg/kg after 1 hour of reperfusion. Plasma interleukin-6
      concentration was estimated by bioassay as a measure of systemic inflammation.
      Plasma endotoxin concentration was determined by use of an amebocyte lysate
      chromogenic assay. Crossreactive immunoglobulin G and M antibodies to the highly
      conserved inner core region of endotoxin were measured by use of an enzyme-linked
      immunosorbent assay. The lung tissue wet-to-dry weight ratio and myeloperoxidase
      concentration were used as markers of edema and neutrophil sequestration,
      respectively. RESULTS: I/R provoked highly significant elevation in plasma
      interleukin-6 concentrations (1351.20 pg/mL [860.16 - 1886.40 pg/mL]) compared
      with controls (125.32 pg/mL [87.76-157.52 pg/mL; P <.0001]), but treatment with
      rBPI(21) 2 mg/kg at onset of reperfusion (715.89 pg/mL [573.36-847.76 pg/mL])
      significantly decreased interleukin-6 response compared with the nontreatment
      group ( P <.016). I/R increased plasma endotoxin concentrations significantly
      (21.52 pg/mL [6.20-48.23 pg/mL]), compared with control animals (0.90 pg/mL [0.00
      2.30 pg/mL; P <.0001]), and treatment with rBPI(21) 4 mg/kg at reperfusion
      significantly decreased endotoxemia (1.30 pg/mL [1.20-2.20 pg/mL]), compared with
      the untreated group ( P <.001). The lung tissue myeloperoxidase level was
      significantly increased in the untreated I/R group (208.18% [128.79%-221.81%]),
      compared with in controls (62.00% [40.45%-80.92%; P <.0001]), and attenuated in
      those treated with rBPI(21) 2 mg/kg (129.54% [90.49%-145.78%; P <.05]). Data
      represent median and interquartile range, comparisons made with the nonparametric
      Mann-Whitney U test. CONCLUSIONS: These findings show that hind limb ischemia
      reperfusion injury is associated with endotoxemia, elevations in plasma
      interleukin-6, and pulmonary leukosequestration. Treatment with rBPI(21) after
      ischemia reduces endotoxemia, the interleukin-6 response, and attenuates
      pulmonary leukosequestration in response to hind limb reperfusion injury.

PMID- 11296341
TI  - Fibrin monomer and fibrinopeptide B act additively to increase DNA synthesis in
      smooth muscle cells cultured from human saphenous vein.
AB  - PURPOSE: We investigated the hypothesis that fibrinogen increased DNA synthesis
      (and cell proliferation) of smooth muscle cells (SMCs) cultured from human
      saphenous vein and that the increased DNA synthesis was attenuated when cells
      were cultured on polymeric collagen. METHODS: SMCs were cultured from human
      saphenous vein on plastic, fibronectin, monomeric, and polymeric collagen.
      Fibrinogen products were prepared by proteolytic digestion. DNA synthesis was
      measured by bromodeoxyuridine incorporation into DNA, cell proliferation by cell
      counting, cyclic adenosine monophosphate by enzyme-linked immunosorbent assay,
      and fibrinopeptide B labeled with iodine 125 used for binding studies. RESULTS:
      Fibrin monomer (0.003-0.1 micromol/L) stimulated a concentration-dependent
      increase in DNA synthesis of up to 10-fold, which could be inhibited by the
      peptide Bbeta15-42. The stimulation of DNA synthesis was highest for cells
      cultured on plastic and lowest for cells cultured on type I collagen polymer.
      Much higher concentrations of fibrinogen (0.3-1 micromol/L) were required to
      effect similar increases in DNA synthesis. Fibrinogen had a particular effect to
      augment DNA synthesis, up to 14-fold, when cells were cultured on monomeric type
      I collagen. This augmented DNA synthesis was inhibited by a neutralizing antibody
      to urokinase-type plasminogen activator. Incubation of cells cultured on collagen
      monomer with fibrinogen resulted in production of fibrinopeptide B.
      Fibrinopeptide B (5 micromol/L) increased DNA synthesis by fourfold and had
      additive effects with fibrin monomer to increase DNA synthesis. Iodinated
      tyrosine fibrinopeptide B bound to SMCs (dissociation constant 0.6 micromol/L).
      CONCLUSION: Cultured human saphenous vein SMCs appear to have high-affinity
      receptors for fibrin monomer and fibrinopeptide B, the engagement of which
      stimulates DNA synthesis. These mechanisms may be pertinent to the association
      between fibrinogen and vein graft stenosis in vivo.

PMID- 11296342
TI  - Basic science curriculum in vascular surgery residency.
AB  - Recognizing the importance of basic science teaching in surgical education, the
      leadership of the Association of Program Directors in Vascular Surgery (APDVS)
      appointed a panel to gather information and to present its findings at the 1999
      annual fall meeting of the Apdvs. A questionnaire was distributed to the program
      directors present. In addition, information was gathered from the American Board
      of Surgery regarding the basic science content in the vascular surgery item pool
      on the vascular surgery qualifying examination (VQE). The vascular surgery unit
      of the surgical resident curriculum was also analyzed. Fifty-three program
      directors (64%) completed the questionnaire. Although only two program directors
      felt that their residents were better prepared to answer basic science questions,
      the results of the Vqe showed that the examinees do not, as a group, perform
      differently on basic science items than on clinical management questions. In
      addition, only a minority of program directors (15%) use a specific method to
      monitor the learning process of their residents. The majority of the program
      directors responding (75%) felt that they were capable of teaching basic science
      to residents. Interestingly, almost half the 53 respondents (47%) said that a
      basic science curriculum should be comprehensive, not exclusively relevant to the
      clinical setting. Vqe content outline and the vascular surgery unit of the
      surgical resident curriculum revealed great emphasis on clinically relevant basic
      science information. The Apdvs panel recommends that a basic science curriculum
      should be comprehensive, yet clinically pertinent, and completely integrated with
      the clinical curriculum. In terms of how to teach basic science in vascular
      residencies, the panel supports teaching conferences that are problem-based with
      a faculty member acting as the "resource person" and with specific goals set for
      the conferences. The panel also suggested establishing a Web site that provides a
      series of questions, the answers of which could be readily available to trainees
      and program directors. such immediate feedback could be of great help to program
      directors to focus the learning process of their residents and monitor its
      progress.

PMID- 11296343
TI  - Ruptured mycotic thoracoabdominal aortic aneurysms: a report of three cases and a
      systematic review.
AB  - We report three cases of ruptured mycotic thoracoabdominal aortic aneurysms
      (TAAAS) and a review of the literature. Escherichia coli and Streptococcus
      pneumoniae (2 patients) were the responsible organisms. Surgical management
      consisted of wide debridement of necrotic tissue and in situ repair with a Dacron
      graft. Antibiotics were administered intravenously in the hospital and continued
      orally after discharge for at least 6 weeks, until clinical and laboratory
      parameters were normalized. A review of the literature showed that Gram-negative
      microorganisms are found in 47% of mycotic TAAAs. A trend toward increased
      mortality for these organisms, compared with Gram-positive microorganisms, was
      observed (P =.09). Lifelong antimicrobial therapy is controversial. No difference
      in survival or recurrence rate was found between series advocating lifelong
      therapy and those suggesting prolonged (6 weeks to 12 months) therapy (median
      follow-up period, 18 and 19 months, respectively). In situ repair with synthetic
      material can be successful if prompt confirmation of infection is obtained, all
      possibly infected tissue is resected, and antibiotic therapy based on sensitivity
      data is administered for a prolonged period. A short-term survival rate as high
      as 82% can be expected with this strategy, but data on long-term survival rates
      are limited. Polytetrafluoroethylene-expanded grafts, homografts, and antibiotic
      bonded grafts may offer advantages over Dacron grafts, but data are insufficient
      to draw conclusions. Careful long-term follow-up is an important element of the
      treatment of these patients. We suggest antibiotic treatment until biochemical
      parameters of inflammation (white cell count, erythrocyte sedimentation rate, or
      C-reactive protein) return to normal and a computerized tomography scan every 3
      months for 1 year, then annually.

PMID- 11296344
TI  - Primary aortoduodenal fistula in a patient with a history of intravesical therapy
      for bladder cancer with bacillus Calmette-Guerin: review of primary aortoduodenal
      fistula without abdominal aortic aneurysm.

PMID- 11296345
TI  - Endovascular repair of an inflammatory abdominal aortic aneurysm complicated by
      aortoduodenal fistulation with an unusual presentation.
AB  - Aortoenteric fistulation (AEF) is a well-documented late complication of open
      abdominal aortic aneurysm (AAA) repair, occurring in between 0.4% and 4% of
      cases. In the absence of an anastomosis, AEF is likely to be rare after
      endovascular aneurysm repair (EVAR) and has only recently been described in the
      literature as a result of mechanical stent failure or migration. We present the
      case of a 61-year-old man who underwent EVAR for an AAA with a "nonspecific"
      periaortic inflammatory mass. Six months postoperatively, an AEF developed,
      presenting with metastatic sepsis followed by septic infective
      thromboembolization to his right leg, and amputation was necessary. His stent was
      well positioned and mechanically intact. We emphasize the need for vigilance
      about the risk of AEF when adopting an endovascular approach to repair the AAA
      with a nonspecific periaortic inflammatory mass and highlight the need for
      awareness about the unusual septic manifestations of AEF.

PMID- 11296346
TI  - The successful surgical treatment of a paradoxical embolus to the carotid
      bifurcation.
AB  - Paradoxical embolism is a rare cause of ischemic stroke. We report the case of a
      67-year-old man who had a saddle embolus to the carotid bifurcation successfully
      treated with emergency embolectomy. Transesophageal echocardiogram revealed a
      large patent foramen ovale and an easily demonstrable right-to-left shunt.
      Subsequent investigations revealed proximal deep venous thrombosis in the left
      femoral and popliteal veins and multiple pulmonary emboli. Long-term
      anticoagulation was instituted for the diagnosis of paradoxical embolism. The
      patient's recovery was uneventful, and he remained neurologically intact. A
      literature review emphasizes the role of transesophageal echocardiography and
      suggests that paradoxical embolism may be a more common cause of stroke than
      previously thought.

PMID- 11296347
TI  - Subclavian steal syndrome from high-output brachiocephalic arteriovenous fistula:
      a previously undescribed complication of dialysis access.
AB  - A 28-year-old dialysis-dependent man presented with episodic vertebrobasilar
      insufficiency. Noninvasive studies demonstrated an estimated 5.8 L/min flow
      through the arteriovenous fistula in his left arm and reversal of flow in the
      left vertebral artery. Surgical reduction of fistula flow resulted in the
      elimination of symptoms and the return of antegrade flow in the left vertebral
      artery. intraoperative invasive monitoring corroborated the pressure gradient
      responsible for his subclavian steal syndrome.

PMID- 11296348
TI  - External transabdominal manipulation of vessels: a useful adjunct with
      endovascular abdominal aortic aneurysm repair.
AB  - During endovascular abdominal aortic aneurysm repair, a severely angulated aortic
      neck or tortuous iliac arteries can make delivery of endografts difficult. We
      describe a simple adjunct in which transabdominal manipulation of vessels is
      used, which can greatly facilitate delivery of these devices in patients with
      challenging anatomy.

PMID- 11296349
TI  - Bypass graft to the midpopliteal artery with a combined anterior and posterior
      approach.
AB  - PURPOSE: The medial supragenicular and infragenicular approaches to the popliteal
      artery were introduced almost 50 years ago and replaced the posterior approach to
      the popliteal artery for distal graft implantation. We review a contemporary
      series of bypass grafts to the midpopliteal artery by use of a combined anterior
      and posterior approach to evaluate its potential clinical benefits. TECHNIQUE:
      After the proximal graft anastomosis is constructed, an incision is made in the
      popliteal fossa to access the midpopliteal artery, the graft is passed into that
      incision, and all but the popliteal incision is closed. The patient is turned,
      the midpopliteal artery dissection is completed, and the graft is anastomosed
      distally. METHODS: Fifty-seven bypass grafts, implanted distally on the
      midpopliteal artery by this technique over a 13-year period, chosen in preference
      to an infragenicular bypass graft in selected patients when a supragenicular
      bypass was not feasible, were assessed in terms of indications for surgery,
      conduit type, complications, length of postoperative hospitalization, and graft
      patency. RESULTS: Bypass grafting originated from the axillary artery in two
      cases, the common iliac artery in one case, and the femoral artery in 54 cases.
      The procedure was performed in five patients with a popliteal trifurcation
      anomaly, nine patients with a blind popliteal segment, 20 patients with limited
      length of autologous vein, and five patients with an above-knee graft infection
      requiring an alternate path for revascularization. Autologous vein was used in 35
      and polytetrafluoroethylene (PTFE) in 19 bypass grafts. Three other patients had
      a composite sequential femoral-popliteal-tibial bypass graft, with PTFE and
      autologous vein. Postoperative (30 day) complications include one death
      (composite sequential), one stroke (PTFE), and one graft thrombosis (saphenous
      vein). The mean postoperative hospitalization for the last 31 patients was 4.2 +/
      3.7 days. In the autologous vein group, the 1-year primary patency rate was 87%,
      and the primary assisted patency rate was 94%. In the PTFE group, the 1-year
      primary patency rate was 72%. Two composite sequential grafts remained patent at
      1 year. CONCLUSIONS: Bypass grafting to the midpopliteal artery with a combined
      anterior and posterior approach offers a safe and effective option to below-knee
      bypass grafting when an above-knee bypass grafting is not feasible. Compared with
      the medial infragenicular incision, the posterior incision results in reduced
      morbidity rates, rapid mobilization, and early hospital discharge.

PMID- 11296350
TI  - The 50th anniversary of abdominal aortic reconstruction.

PMID- 11296351
TI  - Vascular surgery and the American Board of Surgery: political reality.

PMID- 11296352
TI  - The role of the vascular surgeon in endovascular procedures.

PMID- 11296353
TI  - Primum non nocere: Is it always true? The use of absolute ethanol in the
      management of congenital vascular malformations.

PMID- 11296354
TI  - Regarding "Lessons learned from a 6-year clinical experience with superior vena
      cava Greenfield filters".

PMID- 11296355
TI  - [Molecular mechanism of multidrug transporter MDR1: ABC in host-defense
      machinery].

PMID- 11296356
TI  - [Multiplicity and molecular mechanism of substrate recognition by MRP].

PMID- 11296357
TI  - [Organic ion transporter family].

PMID- 11296358
TI  - [Molecular identification of organic anion transporter oatp/LST family].

PMID- 11296359
TI  - [Peptide transporter family].

PMID- 11296360
TI  - [Broad scope amino acid transporters: LAT family].

PMID- 11296361
TI  - [Possibility of immunotherapy against HIV infection].

PMID- 11296362
TI  - [Structure, function and molecular evolution of group I intron ribozyme].

PMID- 11296363
TI  - [A case of multiple cavernous angioma with dementia].
AB  - We reported a 65-year-old man who developed dementia since 50 years of age. His
      consciousness was clear but he was indifferent to his illness. Also, the luck of
      attention was recognized when we underwent examinations and the result of
      intellectual test varied every time we performed. His memory function was almost
      normal on the examination which was performed when he was cooperative. Magnetic
      resonance imaging (MRI) disclosed multiple tiny lesions (more than 130 in all) in
      cerebrum, brainstem, cerebellum and spinal cord. These lesions were compatible
      with multiple cavernous angioma. Most of lesions manifested high-density area on
      cranial CT. Though the multiplicity of foci indicated the possibility of familial
      occurrence, he was considered to be a sporadic case on his lineage investigation
      and the brain MRI of his only son. In this case, neither headache nor seizures
      which were known as the major clinical features of intracerebral cavernous
      angioma was observed. He was diagnosed as having white matter dementia
      characterized by attentional dysfunction, decrement of volition and less memory
      disturbance. We speculated that he developed symptomatic dementia by the sum of
      multiple minor degeneration, especially in frontal lobe white matter, caused by
      repeated minor bleeding from cavernous angiomas.

PMID- 11296364
TI  - [Juvenile parkinsonism with symmetrical hypoperfusion in the cerebellum--a case
      report].
AB  - We report a 24-year-old female presenting levodopa-responsive juvenile
      parkinsonism with symmetrical hypoperfusion in the cerebellum. At the age of 21,
      she noticed difficulty in brushing her teeth and writing with the right hand. She
      developed resting tremor in the right hand. These symptoms were dramatically
      relieved by levodopa. One year prior to the admission, she noticed dystonia and
      drug-induced motor fluctuations and her symptoms became worse. Neurological
      examinations disclosed resting and postural tremor in both hands and the right
      leg. Bradykinesia and cogwheel rigidity were noted on the right side. Deep tendon
      reflexes were slightly increased on the right side, while Babinski sign was
      negative. Slight lateropulsion was observed without retropulsion. Sensory,
      autonomic and cerebellar disturbances were not observed. No abnormalities were
      found in parkins gene or in the genes of spinocerebellar ataxia (SCA) 1,2,3,6,7,8
      and alpha-synuclein. Cranial CT scan and brain MRI were normal, but technetium
      99m ethyl cysteinate dimer (ECD) single photon emission computed tomography
      (SPECT) showed symmetrical hypoperfusion in the cerebellum. Other 5 patients
      presenting juvenile parkinsonism and 10 aged-matched normal controls in our
      hospital did not show hypoperfusion in the cerebellum on ECD SPECT. Cerebellar
      blood flow has not been measured in the previously reported cases of juvenile
      parkinsonism. These results suggested that etiopathogenesis in this patient was
      different from that in previously reported cases.

PMID- 11296366
TI  - [Repeated deterioration of tuberculous meningitis due to a reduction in the
      corticosteroid dosage during chemotherapy].
AB  - A 17-year-old man with a high fever, confusion and neck stiffness was diagnosed
      to have tuberculous meningitis, and was immediately placed on prednisolone (40
      mg/day) as well as standard antituberculosis drugs (isoniazid, rifampicin and
      pyrazinamide). The clinical symptoms improved rapidly and the number of
      cerebrospinal fluid(CSF) cells decreased from 1837/mm3 on admission to 76/mm3 on
      the 7th day. Thereafter the dosage of prednisolone was gradually reduced. As a
      result, however increased nuchal rigidity, papilloedema and an increase in the
      number of CSF cells of 934/mm3 were all observed on the 35th day. Prednisolone
      thus again administered at the original dosage and the patient quickly showed a
      clinical improvement. CSF cells decreased to 271/mm3 on the 70th day. When
      prednisolone was again tapered down, increased nuchal rigidity, abducent nerve
      palsy and papilloedema appeared again with a marked increase in the number of CSF
      cells of 1309/mm3 on the 91th day. Therefore, we continued to treat the patient
      with prednisolone, in addition to the standard antituberculosis treatment, at a
      dose of 80 mg/day and tapered off very slowly over six months. This treatment
      resulted in a marked recovery with no recurrence. In this case, prednisolone was
      indispensable for treating tuberculous meningitis in combination with appropriate
      antituberculosis drugs, though the role of corticosteroids has remained
      controversial over the years. This case might be an example of paradoxical
      progression in tuberculous meningitis.

PMID- 11296365
TI  - [Acquired pendular nystagmus associated with the lesion of tegmentum mesencephali
      in a patient with probable multiple sclerosis].
AB  - A 42-year old woman was admitted to our hospital because of sudden onset of
      dizziness and oscillopsia. Neurologic examination revealed horizontal, binocular
      pendular nystagmus, which increase their amplitude on left lateral gaze. She also
      showed that mild right blephaloptosis, right facial spasms, increased tendon
      reflexes and positive pathological reflexes of four limbs and mild chorea-like
      movement of both feet. MRI showed an abnormal high intensity area on a T2weighted
      and proton density images located at the right tegmentum mesencephali. She was
      diagnosed as clinically probable multiple sclerosis according to the Poser's
      criteria. The nystagmus was suppressed by clonazepam and diazepam. To our
      knowledge, it is a first report of acquired pendular nystagmus associated with
      the lesion of tegmentum mesencephali. We speculate that the involvement of the
      tract of paramedian pontine reticular formation causes the nystagmus and the
      dysfunction of GABAnergic neurons might play an important role of the nystagmus.

PMID- 11296367
TI  - [A case of LGMD2A identified with both western blot analysis and immunostaining
      of calpain 3 in biopsied muscle].
AB  - A 45-year-old housewife had proximal dominant limb muscle weakness from around 25
      years of age. Her parents were cousins. None of family members was affected.
      Progressive muscle weakness and atrophy were prominent at the posterior
      compartments of legs and trunk. Serum CK was moderately elevated. Muscle
      pathology revealed variation in fiber size, moderate increase in numbers of
      internal nuclei and abundant lobulated fibers. On immunostaining using by
      monoclonal antibody against human calpain 3 (NCL-CALP-2 C4; Novocastra) to the
      biopsied muscle, calpain 3 was completely absent in the sarcoplasm, while
      granular debris and in part positive striation were noted in control muscle. By
      Western blot analysis, a band corresponding to 94 kDa of calpain 3 was not
      detected. A genetic analysis of calpain 3 revealed homozygous C-565-G mutation
      (Leu189Val). From the present study. Western blot analysis and immunostaining by
      using calpain 3 antibody were suggested to be useful to diagnose LGMD2A in LGMD
      patients.

PMID- 11296368
TI  - [A Lambert-Faton myasthenic syndrome and subacute cerebellar degeneration with a
      favorable clinical course after resection of small-cell lung cancer].
AB  - A case of Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar
      degeneration (SCD) was associated with small-cell lung cancer (SCLC). The
      patient, a 52-year-old man, who had noticed impotence one year previously, began
      to have ataxic gait, scanning speech and thirst progressing for 3 months,
      followed by weakness of the lower limbs, bilateral blepharoptosis, and double
      vision. Electromyographic studies showed low amplitude of compound muscle action
      potential (CMAP) and waxing phenomenon in high frequency stimulation of the ulnar
      nerve. A chest x-ray showed a mass lesion in the left hilar region, and small
      cell lung cancer was diagnosed on the basis of biopsy specimens. Anti-voltage
      gated calcium channel (VGCC) antibody was positive. Anti-Yo and anti-Hu
      antibodies were negative. The patient was treated by lobectomy and chemotherapy,
      which resulted in improvement in the LEMS and SCD. Anti-VGCC antibody, the CMAP
      amplitude, and waxing phenomenon were improved. Operable cases of SCLC are rare.
      But we propose that anti-neoplastic treatment including resection of the tumor is
      the first choice for the treatment of paraneoplastic syndrome associated with
      SCLC.

PMID- 11296369
TI  - [Progressive cerebellar atrophy following acute antidepressant intoxication].
AB  - A 37-year-old woman presented with acute cerebellar atrophy after ingesting toxic
      doses of tricyclic antidepressants in an attempt of suicide. Two hours after
      ingestion, she was comatose and showed myoclonus of the limbs, and eventually
      developed status epileptics. The patient underwent general anesthesia with
      thiopental, she had hyperpyrexia with elevated muscle enzymes and leukocytosis.
      These clinical and laboratory features suggested that she had serotonin syndrome
      (SS). After recovery from coma and hyperpyrexia that had lasted for 7 days, she
      showed cerebellar ataxia, and progressive cerebellar atrophy of CT scan. As well
      as neuroleptic malignant syndrome, the SS may cause cerebellar degeneration,
      probably due to sustained hyperpyrexia.

PMID- 11296370
TI  - [Central necrosis of the lumbo-sacral segment of the spinal cord associated with
      multiple cholesterin emboli, clinically presenting as acute paraplegia].
AB  - A seventy-six-year-old man suddenly suffered from paraplegia and pain in both
      legs. He had been maintained on hemodialysis and committed a suicide attempt by
      cutting the shunt at the paraplegic attack. He was brought to the emergency ward
      for the treatment of hemorrhagic preshock. Neurological examination demonstrated
      flaccid paraplegia, loss of tendon reflex in the lower extremities, dissociated
      sensory loss below the fourth lumbar level; and incontinence in defecation. MRI
      showed T2 shortening in the ventral spinal cord caudal below the level of the
      eleventh thoracic cord. Postmortem examination confirmed ischemic infarct in the
      central area of the spinal cord, associated with disseminated cholesterin emboli
      in the small arteries. This case was the first MRI demonstration of central
      necrosis caused by cholesterin emboli, and may emphasize the significance of
      cholesterin emboli in the spinal arterial disorders in the aged.

PMID- 11296371
TI  - [Increase in serum creatine phosphokinase following administration of talipexole
      hydrochloride].
AB  - We presented a 60-year-old man with a 12 year history of Parkinson's disease. The
      wearing-off phenomenon occurred 3 years after starting L-dopa. The patient was
      admitted to this unit in order to readjust his medication Administration of
      talipexole hydrochloride was initiated, the patient complained of an aggravation
      of Parkinsonism, and increases in serum creatine phosphokinase (CK) levels to
      1,875 IU/l was observed. The dosage of talipexole was gradually reduced and the
      drug was ultimately discontinued since incomplete neuroleptic malignant syndrome
      was suspected. Serum CK levels then gradually decreased and returned to normal.
      Literature retrieval revealed two cases of neuroleptic malignant syndrome
      following administration of bromocriptine mesilate. Therefore, neuroleptic
      malignant syndrome should be considered when initiation of dopamine agonist
      worsens Parkinsonism.

PMID- 11296372
TI  - [Complications with plasma exchange].
AB  - The value of plasma exchange in the treatment of Guillain-Barre syndrome is well
      established, but in Japan patients often receive double-filtration plasmapheresis
      or immunoadsorption therapy. In this study, we examined the frequency of
      complications with plasma exchange. The complications occurred in 55 of 197
      sessions (28%) during plasma exchange. The most frequent complication was
      transient symptomatic hypotension (16%). There were fever (10%), nausea or
      vomiting (7%), chill (5%), headache (5%), tachycardia (2%) and thromboembolism
      (2%). No significant bleeding was seen in any of the patients. In this study, we
      clarified that the frequency of the complications tended to increase with the
      aging.

PMID- 11296373
TI  - [Painful unilateral gynecomastia in a patient with myotonic dystrophy].
AB  - A 54-year-old patient with myotonic dystrophy presented unilateral painful
      gynecomastia, which occurred 3 months after aggravation of diabetes mellitus.
      Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were
      slightly high. LH was elevated than 2 years before. Breast pain and gynecomastia
      disappeared by daily administration of 10 mg tamoxifen. He could not have
      intramuscular injection therapy because of marked muscle atrophy. Painful
      gynecomastia may be one of the endocrine complications in myotonic dystrophy.

PMID- 11296375
TI  - [Clinical features of late onset dementia with Lewy bodies].
AB  - We conducted a retrospective study to elucidate clinical features of late onset
      dementia with Lewy bodies (DLB). Nineteen patients with DLB of neocortical
      category were neuropathologically diagnosed out of 500 consecutive autopsies at
      Yokufukai Hospital by using the pathological criteria of the consortium on DLB
      International Workshop. Medical history and clinical signs and symptoms were
      reviewed from the medical records. The age at onset was 55-88 years (mean 75.9
      years), the age at death was 62-91 years, and duration of illness was 1-14 years.
      The initial symptoms were memory disturbance (10 cases), delirium (6 cases), gait
      disturbance (3 cases), visual hallucination (3 cases). We divided nineteen cases
      of DLB into two group: the age of onset was under 75 years (9 cases) and over 76
      years (10 cases). The early onset group showed parkinsonism (67%), and visual
      hallucination (55%). The sensitivity of the clinical diagnosis of probable DLB
      based on DLB international workshop consensus criteria was 67%. On the other
      hand, the late onset group (10cases) presented with delirium (70%), parkinsonism
      (20%), and visual hallucination (30%). The sensitivity of a clinical diagnosis of
      probable DLB was 30%. Our results indicated considerable difficulty of the
      diagnosis of late onset DLB cases by the consensus criteria, requiring more
      sensitive criteria and diagnostic tests for DLB.

PMID- 11296374
TI  - [Immunoadsorption therapy with TR-350 (tryptophan column) for Guillain-Barre
      syndrome: investigation including serum antiganglioside antibody assay].
AB  - Immunoadsorption therapy (IAT) using TR-350 was performed for 14 patients with
      Guillain-Barre syndrome (GBS). Presence of serum antiganglioside antibodies (AGA)
      was investigated in all the patients in the acute phase. In 14 patients studied,
      6 men and 8 women, ages from 24 to 74 years(mean, 42.5 years), 7 patients had
      suffered from common cold and 3 from diarrhea before neurological onset.
      Ophthalmoplegia was seen in 6 patients, facial palsy in 6, bulbar palsy in 3 and
      cerebellar sign in 2. Functional grade scores (FGS) by Hughes et al. of the
      patients were from 5 to 1 (mean, 3.3). In 4 patients, whose FGS were 1 or 2, IAT
      were performed, because of worsting of bulbar palsy, bilateral facial palsy and
      limb weakness. Relapse occurred in one patient. IAT was started from 2 to 18 days
      (mean, 8.4) after neurological onset and performed 3 to 14 times (mean, 7.5) for
      each patient. Mean FGS improved from 3.3 to 2.1 after IAT. The mean time to
      improve 1 grade was 10.3 days and mean time to improve 2 grades was 39.0 days.
      The mean FGS after 1 month was 1.4 and that after 3 months was 0.4. Some of 14
      patients had elevated titers of AGA in sera in the acute phase. Four patients had
      anti-GQ1b IgG antibody and showed external ophthalmoplegia. One patient with anti
      GD1b IgG antibody had cerebellar signs as well as peripheral neuropathy. Those
      AGAs decreased after IAT in parallel with improvement. IAT is an effective
      treatment in acute phase of GBS.

PMID- 11296376
TI  - [Clinical study of spinal dural arteriovenous fistula-with special reference to
      neurological symptoms and magnetic resonance imaging].
AB  - We have evaluated the backgrounds, neurological symptoms, signs, and magnetic
      resonance images (MRI) in six cases of spinal dural arteriovenous fistula. The
      subjects were 2 males and 4 females, and the mean age was 67.2 years old. The
      cardinal subjective symptoms were progressive motor weakness of lower extremities
      (2 cases), paroxyomal weakness of lower extremities (3 cases), sensory
      disturbance of polyneuritic type (2 cases), and intermittent claudication (1
      case). Administration of beverages and drugs, which might include vasodilators
      and taking baths, worsened the symptoms and signs in 3 cases and 2 cases
      respectively. Concerning to MRI findings, high signal intensities or swellings
      were observed at mid-thoracic area to upper conus of the spinal cord in all
      cases. These changes, which would be induced by edema caused by high venous
      pressure, were especially prominent in the central area of the cords. By these
      mechanisms, sensory disturbance like polyneuritic type caused by the disturbance
      in deep areas of posterior columns might more prominent than the disorder of
      spinothalamic tracts placed in superficial areas of cord in the early stage of
      the disease. These abnormal intensities of MRI were higher than the level of
      clinical symptoms and signs. The difference was about 6.5 segments. For this
      reason, the upper border of the spinal cord lesions could not be identified by
      the neurological symptoms. Although the clinical features and MRI findings are
      relatively characteristic, flow void signs by high resonance MRI and abnormal
      blood vessels by spinal angiography will be necessary to diagnose this disease
      confidently.

PMID- 11296377
TI  - [Recurrent episodes of fever of unknown origin as temporal lobe epilepsy].
AB  - A 67-year-old woman was admitted to our department for the recurrent fever of
      unknown origin that occurred once approximately every 1 month for the last 3
      years. No clinical and laboratory abnormality were found, except an interictal
      EEG showing fronto-temporal spike discharges. During hospitalization a
      characteristic febrile episode was accompanied by automatism, thereby, it became
      clear that the undetermined periodic febrile episodes were due to temporal lobe
      epilepsy. In this case, the thermoregulatory center of the hypothalamus might be
      symptomatic zone of temporal lobe epilepsy.

PMID- 11296378
TI  - [A prospect of activities of the Japanese Respiratory Society in the 21st
      century].

PMID- 11296379
TI  - [Beta-defensins in plasma and bronchoalveolar lavage fluid in patients with non
      tuberculous mycobacterium infection].
AB  - We measured the levels of beta-defensin 1 and 2 (HBD-1, 2), novel antimicrobial
      peptides in plasma and in bronchoalveolar lavage fluid (BALF) from patients with
      with non-tuberculous mycobacterium infection (NTM). Plasma HBD-2 levels in NTM
      patients before treatment were higher than those in the controls, while the HBD-1
      levels were similar to the control levels. High levels of HBD-2, but not of HBD
      1, in BALF were also observed in NTM patients. In NTM, a positive correlation was
      found between HBD-2 levels in BALF and plasma, and also between HBD-2 and IL-1
      beta levels in BALF. NTM patients with cavities or ectasia on chest radiography
      had higher HBD-2 levels in BALF than those without. Plasma HBD-2 levels in NTM
      patients were markedly decreased after successful treatment, while those of
      patients with an intractable mycobacterium infection maintained the same high
      plasma HBD-2 levels as those before treatment. These findings suggest that HBD-2
      may participate in the host defense and plasma HBD-2 levels may reflect disease
      activity in pulmonary NTM.

PMID- 11296380
TI  - [Effects of carbocisteine on airway inflammation and related events in SO2
      exposed rats].
AB  - Airway inflammation leads to secretion of abnormal mucous glycoprotein and
      ciliary injury. To investigate the possible usefulness of carbocisteine against
      airway inflammation and events related to it, we conducted a study in SO2-exposed
      rats of the effects of carbocisteine and ambroxol, as an active control drug, on
      components of mucous glycoprotein (fucose, sialic acid and protein) in
      bronchoalveolar lavage fluid (BALF); on infiltration and activation of
      inflammatory cells in BALF; on tracheal and bronchial-ciliary lesions; and on
      cAMP levels in tracheal and alveolar tissues. Carbocisteine inhibited or improved
      all SO2-induced changes tested, and dosages of 125 and 250 mg/kg b.i.d. reduced
      fucose, sialic acid and protein contents, inflammatory cells (as markers of
      inflammation), free radicals, and elastase activity in BALF, and suppressed the
      development of ciliary lesions of the tracheal and bronchial mucosa, while
      ambroxol (10 mg/kg b.i.d.) showed no such effects. In addition, carbocisteine
      improved cAMP levels in the tracheal and alveolar tissues. These results indicate
      that carbocisteine is able to prevent the development of inflammation-related
      respiratory disease in this rat model, and that this remission of airway
      inflammation may be associated with carbocisteine-induced normalization of cAMP
      levels in tracheal and alveolar tissues as well as with its mucoregulant and anti
      inflammatory effects. In conclusion, carbocisteine has a unique mucoregulant
      action and inhibits SO2-induced airway inflammation in a manner different from
      that of ambroxol.

PMID- 11296381
TI  - [Analysis of patients with middle lobe and lingular syndrome complicated with
      nontuberculous mycobacterosis, chronic sinusitis, or bronchopulmonary
      tuberculosis].
AB  - The clinical characteristics and chest CT scan findings in 77 cases of middle
      lobe and lingular syndrome, many of which were complicated with nontuberculous
      mycobacteriosis (21 cases, 27.3%), chronic sinusitis (16, 20.8%), or
      bronchopulmonary tuberculosis (11, 14.3%) are reported. Sixteen (76.2%) cases
      complicated with nontuberculous mycobacteriosis and 14 (87.5%) cases complicated
      with chronic sinusitis had granular shadows with dilated bronchi of both middle
      lobe and lingular in their chest CT scans. Granular shadows with a thickening of
      the bronchial wall or dilated bronchi were common characteristics of the chest CT
      scans of the patients with nontuberculous mycobacteriosis. However, cicatrization
      atelectasis of either middle lobe or lingular was the most common finding in
      patients with bronchopulmonary tuberculosis.

PMID- 11296382
TI  - [A case of minocycline-induced eosinophilic pneumonia presenting with multiple
      white eosinophilic plaques in the tracheobronchial mucosa].
AB  - A 45-year-old man was admitted with a severe dry cough and fever. He had been
      given 100 mg/day of minocycline and other drugs for 9 days to treat hematopyuria.
      Chest X-ray film showed multiple nodular shadows with diffuse reticular shadows.
      After all the drugs were discontinued, the fever and the shadows improved, but
      the severe dry cough persisted. The day 4 bronchofiberscopic findings included
      multiple white plaques in the tracheobronchial mucosa. Punch biopsy specimens
      obtained from the white plaques revealed severe eosinophil infiltration, and the
      eosinophil count in the bronchoalveolar lavage fluid had increased (differential
      count 23%). After three days of 125 mg/day of methylprednisolone sodium succinate
      injection therapy, the severe cough, the X-ray shadows and the white plaques
      disappeared. With a positive result in the lymphocyte migration inhibition test,
      the patient's condition was diagnosed as minocycline-induced eosinophilic
      pneumonia.

PMID- 11296383
TI  - [A case of relapsed small cell lung cancer recognized by simple metastasis to the
      duodenum].
AB  - We describe a case of relapsed small cell lung cancer (SCLC) recognized by a
      duodenal tumor, its probable metastasis. A 69-year-old man was admitted to Keio
      University Hospital complaining of persistent sputum production in September,
      1996. A diagnosis of SCLC of the left lung invading the mediastinum was based on
      a transesophageal biopsy. Chemotherapy consisting of CDDP and VP-16 followed by
      thoracic irradiation at a total dose of 50 Gy was performed from October 1996 to
      August 1997, resulting in CR (Complete Response) of the tumor. In April of 1999,
      a mass surrounding the duodenum was found through an abdominal CT survey for
      tumor relapse, but no other tumors were detected in a series of CT scans or
      inbone scintigraphy. Subsequent fiberscopy of the upper gastrointestinal tract
      revealed an ulcerative tumor extensively invading the mucosa of the duodenal
      bulb. Biopsy specimens obtained from the duodenal tumor showed small-cell
      carcinoma with features similar to those of SCLC found in 1996, suggesting that
      SCLC of the left lung metastasized to the duodenal wall. Chemoradiotherapy with 4
      cycles of CDDP and VP-16 followed by abdominal irradiation at a dose of 30 Gy was
      given again from May to September 1999, producing good PR (Partial Response).
      Although metastasis of SCLC to the duodenum seldom occurs, this report indicates
      that its early detection and effective treatment may prevent serious symptoms
      caused by obstruction of the duodenum or the papilla Vater.

PMID- 11296384
TI  - [A case of lung adenocarcinoma showing diffuse air-space consolidation with
      idiopathic interstitial pneumonia].
AB  - Routine chest radiography demonstrated abnormal opacities in the right lower lung
      field of a 54-year-old man with idiopathic interstitial pneumonia. A high
      resolution chest CT scan showed diffuse air-space consolidation in the right
      lower lung with replacement of a honeycomb area. The diagnosis was
      adenocarcinoma, and a right lower lobectomy was performed. Histopathologic
      examination showed moderately differentiated adenocarcinoma and the pathological
      stage was T3 N0 M0 (Stage IIB). About 1 year later, the cancer recurred with
      diffuse air-space consolidation in the whole of the right lung and the left
      middle and lower lung, which resulted in the patient's death. It was difficult to
      discriminate between an acute change for the worse of idiopathic interstitial
      pneumonia and a recurrence of lung cancer on the basis of the CT findings in this
      patient. It is important to elucidate the CT features of lung cancer associated
      with idiopathic interstitial pneumonia.

PMID- 11296385
TI  - [A case of small cell lung cancer with paraneoplastic cerebellar degeneration and
      anti-voltage-gated calcium channel antibody].
AB  - A 55-year-old man presenting with 4 weeks of progressive dysarthria, gait ataxia
      and vertigo was admitted to our hospital. Chest X-ray films revealed a mass
      shadow in the right upper lobe of the lung, and transbronchial brushing specimens
      showed small-cell carcinoma. Extensive examination revealed metastatic lesions in
      the mediastinal lymph nodes and liver, but brain MRI showed no findings
      suggestive of metastasis or atrophy. A diagnosis of PCD associated with SCLC was
      made, and the patient had a high titer of anti-P/Q-type VGCC antibody. He was
      treated by chemotherapy and radiation therapy, which resulted in a transient
      improvement in the PCD symptoms.

PMID- 11296386
TI  - [A case of radiologically negative small-cell lung carcinoma successfully
      detected early by whole-body FDG-PET].
AB  - A 68-year-old man was referred to our hospital after being treated for early
      gastric cancer to investigate the causative malignancy, as his serum
      carcinoembryonic antigen (CEA) level was increased. Chest radiography showed no
      abnormal opacities. Subsequently, a whole-body FDG-PET was performed, which
      detected some tiny lesions in the mediastinum and the right lower lung field. A
      diagnosis of small-cell lung carcinoma was made after mediastinoscopic and
      bronchoscopic examinations. After chemoradiotherapy, the previously abnormal
      uptake of FDG was attenuated and the bronchoscopic appearance was improved, while
      the serum CEA and NSE levels returned to normal. Our findings demonstrated that
      whole-body scanning by FDG-PET could be useful for early detection of lung
      cancer, especially in cases of small-cell lung cancer.

PMID- 11296387
TI  - [Lung cancer metastasis to the gingiva].
AB  - A 70-year-old man was referred to our hospital complaining of left gingival
      tumors with bleeding, halitosis and impediments to eating and speaking. Tumors
      were also found in both lungs, the stomach, the intestines and the right adrenal
      gland. Biopsies of the gingiva and the stomach pointed to undifferentiated
      carcinoma. Although the patient was treated with carboplatin plus 5-fluorouracil,
      the gingival tumors did not change in size. Subsequently, the gingival tumors
      were irradiated with a total dose of 39 Gy, and disappeared completely. The
      patient died 78 days later of hemorrhage of the digestive tract. Postmortem
      examination revealed that the primary tumor was in the left lung. Nineteen cases
      of lung cancer metastatic to the gingiva have been reported. The prognosis in all
      was very poor, and the QOL was compromised. However, several cases have improved
      with therapy to the gingiva. We believe that initial therapy should be directed
      at metastatic gingival tumors of the lung.

PMID- 11296388
TI  - [A case of drug-induced interstitial pneumonitis in rheumatoid arthritis treated
      with bucillamine].
AB  - We report a case of bucillamine-induced interstitial pneumonitis in a 57-year-old
      woman. Rheumatoid arthritis was diagnosed in May 1999, and she was treated with
      bucillamine from June 1999, with a favorable outcome. After complaining of cough,
      fever, and dyspnea in October, she was admitted to this hospital. Blood gas
      analysis showed severe hypoxemia. The chest CT revealed both bilateral diffuse
      ground-glass opacity along the bronchovascular bundles, and thickening of the
      interlobular septa. We suspected bucillamine-induced interstitial pneumonitis
      from the findings of the CT scan, BALF and TBLB, and also from the improvement of
      PaO2 after the withdrawal of bucillamine. We treated the patient with
      prednisolone, and a favorable response was noted. A lymphocyte stimulation test
      using bucillamine was positive. A video-assisted thoracic surgery lung biopsy
      showed findings compatible with acute interstitial pneumonia without the
      association of hyaline membrane formation. A focal fibrosis was also observed. We
      believe that this is the only reported case of pathologically proven bucillamine
      induced interstitial pneumonitis, in which a surgical lung biopsy was performed.

PMID- 11296389
TI  - [Two cases of acute eosinophilic pneumonia--analyses of cytokines in BALF before
      and after treatment].
AB  - Acute eosinophilic pneumonia (AEP) has been well recognized as sudden onset
      respiratory failure characterized by an increased eosinophilic cell count in the
      bronchoalveolar lavage fluid (BALF). Although several lines of research have
      demonstrated that the Th2 cytokine network is likely to play a pivotal role in
      the development of AEP, that mechanism has not been clearly understood yet.
      Previous reports published in Japan demonstrated that the BALF CD4/CD8 ratio in
      patients with AEP ranged between 1.1 and 5.8. In this report, we describe 2 cases
      of AEP in which the CD4/CD8 ratios were 0.3 and 7.8 when present. We measured IL
      4, IL-5, IL-10 and IFN gamma in the BALF before and after treatment in these
      patients. IL-5 decreased drastically after the treatment phase, while the other
      cytokines did not change much. We concluded that the IL-5 concentration in the
      BALF is probably related to the development of AEP. In addition, we also
      speculated that the CD4/CD8 ratio in BALF from patients with AEP may be affected
      whether a patient has an atopic background or not.

PMID- 11296390
TI  - [A case of post-thymomectomy myasthenia gravis after extrapleural pneumonectomy
      for invasive thymoma which necessistated long-term mechanical ventilation].
AB  - The patient was a 58-year-old male with invasive thymoma which had disseminated
      in the left thorax and was histologically a polygonal cell type lesion. While the
      serum value of anti-acetylcholine receptor antibody was high before surgery,
      there were signs of myasthenia gravis. After preoperative chemotherapy, a
      thymectomy and left panpleuropneumonectomy were conducted. Forty days after
      surgery, the patients suffered post-thymomectomy myasthenia gravis, which
      necessitated mechanical ventilation for 6 months. Despite steroid therapy and 17
      plasmapheresis procedures the tidal volume increased by little more than 200-250
      ml during that time. The causes of ventilatory failure, therefore, were probably
      decreased pulmonary function due to extrapleural pneumonectomy and the myasthenia
      gravis. According to the literature, polygonal cell type thymomas with high serum
      levels of anti-acethycholine receptor antibody have higher incidences of post
      thymomectomy myasthenia gragvis than other ones. Therefore, the risk of post
      thymomectomy myasthenia gravis should be kept in mind when extrapleural
      pneumonectomy for invasive thymoma is being considered, especially in the cases
      of this type.

PMID- 11296391
TI  - [Clinical usefulness of antigen-captured ELISA method using mouse anti
      Trichosporon asahii monoclonal antibody D-8 for diagnosis of summer-type
      hypersensitivity pneumonitis].
AB  - In the present study, we assessed the clinical usefulness of the antigen-captured
      ELISA method using mouse anti-Trichosporon asahii monoclonal antibody D-8 in 193
      patients with summer-type hypersensitivity pneumonitis (SHP) and in 127 healthy
      volunteers. When the cut-off value was determined as 0.15, the diagnosis of SHP
      was accurately made by this method in 168 of 193 SHP patients. The sensitivity
      and specificity of the diagnosis of SHP determined by this method were 87.0% and
      96.1%, respectively. We concluded that this ELISA method is a useful technique
      for the diagnosis of SHP when the possibility of SHP is recognized during the
      course of a case.

PMID- 11296392
TI  - [Case report of surgically treated dumbbell-type schwannoma arising in the right
      brachial plexus with von Recklinghausen disease].
AB  - We encountered a patient with dumbbell-type schwannoma arising in the right
      brachial plexus with von Recklinghausen disease. The patient was a 9-year-old
      girl. An abnormal shadow was detected high in the thoracic cavity by thoracic
      radiography. Thoracic CT and MRI demonstrated at the apex of the thoracic cavity
      a tumor measuring 9.0 x 6.0 cm, which was diagnosed as a dumbbell-type neurogenic
      tumor derived from the brachial plexus. Most cases of such tumors growing inside
      and outside the spinal cavity have reportedly been treated in a single surgical
      procedure. However, since the tumor in this patient was large, the intrathoracic
      portion was removed first in order to minimize the magnitude of the surgical
      invasion. The residual intraspinal tumor was removed during subsequent surgery.
      No neurological problems were observed after surgery. Patients with dumbbell-type
      schwannomas arising in the right brachial plexus appear to be very rare, and this
      patient was considered noteworthy.

PMID- 11296393
TI  - [Sex, education, and races as risk factors of Alzheimer's disease].

PMID- 11296394
TI  - [Alzheimer's disease and arteriosclerosis].

PMID- 11296395
TI  - [Molecular mechanism of deposition of amyloid beta-protein].

PMID- 11296396
TI  - [Recent development of anti-dementia drugs].

PMID- 11296397
TI  - [Clinical features of myelitis in patients with atopic symptoms].
AB  - It is rare to see atopic symptoms in patients with multiple sclerosis(MS).
      However, it has been reported that in atopic patients, particularly in patients
      with atopic dermatitis, a benign myelitis occasionally occurs. In the present
      report, three atopic patients with myelitis were studied clinically and
      neuroradiologically. All the patients were adult men(Case 1, 2, and 3 were 41
      year-old, 31-year-old, and 34-year-old, respectively), and all of them had
      bronchial asthma without histories of atopic dermatitis. Their manifestations
      were not severe and were only numbness of upper and/or lower extremities. There
      was no motor weakness, ataxia, or urinary incontinence. MRI studies revealed a T2
      high intensity lesion in the high cervical spinal cord in the two patients(Case 2
      and 3) and a T2-high intensity lesion in the lumber spinal cord in the remaining
      patient(Case 1). Their clinical courses were essentially all benign and well
      responsive to steroid therapy. Although myelitis of these patients may be a first
      attack of MS, their findings appear to support a recently emerging concept of the
      atopic myelitis.

PMID- 11296398
TI  - [Influence of intubation maneuver with or without premedication for intracranial
      hemorrhage with unconsciousness].
AB  - PURPOSE: To clarify the influence of intubation maneuver with or without
      premedication for intracranial hemorrhage with unconsciousness. METHODS: Between
      May 1995 and May 2000, we analyzed retrospectively 46 patients who had received
      intubation for unconsciousness and were found non-traumatic intracranial
      hemorrhage by head computer tomography at the Trauma and Critical Care Center,
      National Defense Medical College. They were divided into two groups, Drug group
      in which drugs were used before intubation and Control group which were intubated
      without drugs. Physical findings on admission, head CT findings, Glasgow Outcome
      Score(GOS) at discharge were analyzed between the groups. RESULTS: There were no
      significant differences for background of subjects between the groups. In the
      Drug group, diazepam, pentazocine, lidocaine, nifedipine and nicardipine were
      used before intubation. GOS in the Control group was significantly greater than
      in the Drug group(p < 0.01). CONCLUSION: In case of intubation for unconscious
      patients who may suffer intracranial hemorrhage, using premedication leads to
      favorable outcome.

PMID- 11296399
TI  - [YAG laser-induced reperfusion of photothrombotic middle cerebral artery
      occlusion in rats].
AB  - The laser-driven photochemical occlusion of middle cerebral artery(MCA) is much
      easier, and less traumatic than standard electrocautery or even clip methods,
      while the infarct size is fairly reproducible. This study aimed to establish the
      system for YAG laser-induced reperfusion of photothrombotic MCA occlusion. Male
      spontaneously hypertensive rats(5-7 months old, 350-450 g) were anesthetized with
      halothane, endotracheally intubated, and mechanically ventilated. The
      photosensitizing dye rose bengal(20 mg/kg body weight) was administered
      intravenously over 90 sec starting simultaneously with 3 min of krypton laser
      irradiation(568 nm, 20 mW). The irradiated middle cerebral artery was completely
      occluded by an intraluminal thrombus. A YAG laser operating at 355 nm(16 mW, 15
      Hz) was focused with a cylindrical lens and positioned with a mirror onto the
      occluded distal MCA. This YAG laser irradiation for approximately 3 min caused
      reperfusion of the thrombosed distal MCA. We demonstrated a novel method of
      reperfusion in the photothrombotic MCA occlusion model. This reperfusion model
      should facilitate study of the therapeutic window for reversibility in thrombotic
      stroke.

PMID- 11296400
TI  - [Polyneuropathy index-revised in the evaluation of diabetic neuropathy].
AB  - The polyneuropathy index-revised(PNI-R), based on 8 electrophysiological
      parameters(conduction velocities and F-latencies), was constructed to obtain an
      overall estimation of peripheral nerve conduction in diabetic patients, taking
      PNI as a model. PNI was calculated as a mean percentage of the normal on 12
      velocity or latency parameters on motor nerve conduction studies. PNI-R is
      composed of 8 parameters; motor nerve conduction velocities in the forearm or leg
      segment and F-wave latencies after wrist or ankle stimulation concerning to the
      median, ulnar, peroneal and posterior tibial nerves. F-wave latencies were
      adjusted to 160 cm height and used reciprocals to compare with the normal values.
      Subjects were 101 patients with diabetes mellitus. Correlation of PNI-R or PNI
      with other parameters or indices on conventional sensory and intrafascicular
      conduction studies or items concerning to the diabetes mellitus were studied.
      Coefficient of correlation between PNI-R and PNI was as high as 0.97. The mean
      value of PNI-R was 0.6% smaller than PNI. This was presumably due to the greater
      influence of the peroneal parameters, weighted more in PNI-R than in PNI.
      Peroneal nerve is known to be sensitive to various neuropathies, and is often
      damaged independently. Each parameter composing PNI-R had a close relationship
      with PNI-R itself. Mutual independence between 8 parameters was considered to be
      enough. Among neuropathic signs Achilles tendon reflex in particular, and among
      diabetic complications retinopathy in particular, had a high degree of
      correlation with PNI-R. These results were identical both with PNI-R and PNI. We
      can save 20-30% of time in measuring PNI-R as compared to measure PNI, and the
      usefulness of PNI-R was as well as PNI. Therefore, using PNI-R as substitute for
      PNI is considered to be appropriate in the evaluation of diabetic polyneuropathy.
      Between parameters concerning to the median nerve F-wave latency correlated less
      with PNI-R than motor nerve conduction velocity in the forearm segment.
      Presumably this was owing to an unrecognized subclinical carpal tunnel syndrome,
      often observed in patients with diabetes mellitus. PNI-R will be an excellent
      index to express the function of peripheral nerve conduction, which can be
      retarded by the axonal degeneration in diabetes mellitus.

PMID- 11296401
TI  - [Neuroprotective effect of a neurotoxin, 3-nitropropionic acid, against hypoxic
      damage to the gerbil hippocampus: neuroprotection after the onset of hypoxic
      depolarization].
AB  - Ischemic/hypoxic tolerance induced by a subtoxic dose of neurotoxin, 3
      nitropropionic acid(3-NPA), was recently reported as "chemical preconditioning".
      We previously showed that the neuroprotective effect by chemical preconditioning
      with 3-NPA was induced by prolonging the delay to hypoxic depolarization (HD) via
      activating adenosine receptors. In this study, we electrophysiologically assessed
      whether the protective effect of chemical preconditioning was potent after the
      onset of HD. An in vitro hippocampal slice model from adult gerbils was used to
      study the delay to HD during hypoxia and the recovery of synaptic responses after
      hypoxia. Hypoxia was sustained until a fixed period(8 min) following HD. These
      responses were examined in control slices and slices pretreated with subtoxic
      dose of 3-NPA(4 mg/kg) intraperitoneally at 3 hours prior to slice preparation.
      The delay to hypoxic depolarization in 3-NPA treated slices was significantly
      prolonged(p < 0.05). The field excitatory postsynaptic potential recovery after a
      fixed period of hypoxia under HD was also significantly improved in the 3-NPA
      treated group(48.6 +/- 23.8%) compared with the control group(29.2 +/- 12.2%) (p
      < 0.05). This finding indicates that chemical preconditioning with 3-NPA induces
      the neuroprotective effect against hypoxic damage after as well as before the
      onset of HD to the hippocampus.

PMID- 11296402
TI  - [A thyrotoxic myopathy accompanied with unusual muscle symptoms and MRI muscle
      findings].
AB  - We report a patient with thyrotoxic myopathy associated with unusual muscle
      symptoms. A 29-year-old man developed hyperhidrosis, diarrhea, increase in
      appetite, and excitability in July, 1999. In August, he experienced muscle
      stiffness in bilateral lower extremities after maintaining postures such as
      driving a car or sitting on a chair. He was admitted to our hospital, in January,
      2000. On physical examination, goiter was noted. Neurological examination was
      normal except for proximal muscle weakness. Laboratory test showed elevated free
      T3 and free T4, decreased TSH. TSH receptor antibody was increased. MRI of lower
      extremities revealed atrophy of bilateral biceps femoris. Muscle strength
      increased gradually after an oral administration of thiamazole 30 mg/day, and
      muscle stiffness disappeared. The clinical features of this patient and
      differential diagnosis were discussed.

PMID- 11296404
TI  - [A case of arteriovenous malformation associated with venous malformation].
AB  - A case of arteriovenous malformation associated with venous malformation is
      reported. A 35-year-old male patient suffered intracerebral hemorrhage in the
      left occipital with acute subdural hematoma. Angiography showed an arteriovenous
      malformation fed by the left middle cerebral artery. The hematoma and nidus was
      operatively removed. He also had a venous malformation in the left temporal lobe.
      This rare case is reported with some discussion.

PMID- 11296403
TI  - [A case of Miller Fisher syndrome with pharyngeal palsy as an initial symptom].
AB  - We report herein a rare case of Miller Fisher syndrome with pharyngeal palsy as
      an initial symptom. A 68-year-old man admitted to our hospital with pharyngeal
      palsy two weeks after a respiratory infection. He subsequently developed ataxic
      gait, paresthesia in the upper limbs and ophthalmoplegia. Double-filtrated
      plasmapheresis had been performed four times and all the symptoms subsided within
      two months. In the acute phase of the disease, the titers of anti-GQ1b and GT1a
      antibodies were elevated. The titer of anti-GT1a antibody was higher than that of
      anti-GQ1b antibody. Recently, the activity of serum anti-GT1a antibody has been
      supposed to be associated with pharyngeal palsy. In the present case, higher
      titer of anti-GT1a antibody compared with that of anti-GQ1b antibody could
      possibly cause pharyngeal palsy as an initial symptom of Miller Fisher syndrome.

PMID- 11296405
TI  - [Chronic subdural hematoma presenting visual disturbance: a case report].
AB  - The authors reported a rare case of chronic subdural hematoma presenting
      bilateral visual impairment caused by papilledema. A 49-year-old man was admitted
      to our department due to left blurred vision. On admission, ophthalmological
      examination revealed visual acuity disturbance on the left eye, bilateral nasal
      visual field defect and papilledema. CT scan and MRI demonstrated bilateral
      subdural hematoma. No remarkable findings were detected on cerebral angiography.
      After evacuation of bilateral subdural hematomas, his visual symptoms recovered.
      In this report, we discuss the mechanism of visual impairment caused by chronic
      subdural hematoma.

PMID- 11296406
TI  - [A case of crossed aphasia with echolalia after the resection of tumor in the
      right medial frontal lobe].
AB  - We report a right-handed woman, who developed a non-fluent aphasia after
      resection of astrocytoma (grade III) in the right medial frontal lobe. On
      admission to the rehabilitation department, neurological examination revealed
      mild left hemiparesis, hyperreflexia on the left side and grasp reflex on the
      left hand. Neuropsychologically she showed general inattention, non-fluent
      aphasia, acalculia, constructional disability, and mild buccofacial apraxia. No
      other apraxia, unilateral spatial neglect or extinction phenomena were observed.
      An MRI demonstrated resected areas in the right superior frontal gyrus,
      subcortical region in the right middle frontal gyrus, anterior part of the
      cingulate gyrus, a part of supplementary motor area. Surrounding area in the
      right frontal lobe showed diffuse signal change. She demonstrated non-fluent
      aprosodic speech with word finding difficulty. No phonemic paraphasia, or
      anarthria was observed. Auditory comprehension was fair with some difficulty in
      comprehending complex commands. Naming was good, but verbal fluency tests for a
      category or phonemic cuing was severely impaired. She could repeat words but not
      sentences. Reading comprehension was disturbed by semantic paralexia and writing
      words was poor for both Kana (syllabogram) and Kanji(logogram) characters. A
      significant feature of her speech was mitigated echolalia. In both free
      conversation and examination setting, she often repeated phrases spoken to her
      which she used to start her speech. In addition, she repeated words spoken to
      others which were totally irrelevant to her conversation. She was aware of her
      echoing, which always embarrassed her. She described her echolalic tendency as a
      great nuisance. However, once echoing being forbidden, she could not initiate her
      speech and made incorrect responses after long delay. Thus, her compulsive
      echolalia helped to start her speech. Only four patients with crossed aphasia
      demonstrated echolalia in the literature. They showed severe aphasia with
      markedly decreased speech and severe comprehension deficit. A patient with a
      similar lesion in the right medial frontal lobe had aspontaneity in general and
      language function per se could not be examined properly. Echolalia related to the
      medial frontal lesion in the language dominant hemisphere was described as a
      compulsive speech response, because some other 'echoing' phenomena or compulsive
      behavior were also observed in these patients. On the other hand, some patients
      with a large lesion in the right hemisphere tended to respond to stimuli directed
      to other patients, so called 'response-to-next-patient-stimulation'. This
      behavior was explained by disinhibited shift of attention or perseveration of the
      set. Both compulsive speech responses and 'response-to-next-patient-stimulation'
      like phenomena may have contributed to the echolalia phenomena of the present
      case.

PMID- 11296408
TI  - [Intracranial lipoma in the sylvian fissure with convulsion].

PMID- 11296407
TI  - [An operated case of medial temporal lobe epilepsy associated with
      schizencephaly].
AB  - A 24-year-old male of medial temporal lobe epilepsy associated with
      schizencephaly was presented. He developed complex partial seizure after head
      trauma at the age of a year and 7 months, which became intractable at the age of
      13 year. MRI demonstrated a schizencephalic cleft in the right peri-Rolandic
      area, cortical dysplasia in the right medical parietal and occipital lobes, and
      right hippocampal atrophy. Scalp-recorded EEG failed to localize the ictal onset
      zone. Interictal FDG-PET and ECD-SPECT indicated hypometabolism and hypoperfusion
      of the right entire temporal lobe, and ictal ECD-SPECT increased perfusion of
      this area. Chronic subdural electrode recording clearly demonstrated that ictal
      onset zone was located not on the schizencephalic cleft or its surrounding cortex
      but on the right medial temporal lobe. Following right anterior temporal
      lobectomy with hipppocampectomy, seizure control became easy. For the
      identification of the epileptogenic zone in patients with schizencephaly, chronic
      subdural electrode recording is mandatory.

PMID- 11296409
TI  - [Localized cortical atrophy in primary lateral sclerosis].

PMID- 11296410
TI  - ABT-773 overview.

PMID- 11296411
TI  - Telithromycin--an innovative ketolide antimicrobials.

PMID- 11296412
TI  - Azithromycin: a new 15-membered macrolide.
AB  - Azithromycin is the sole member of the macrolide sub-class, the azalides. Due to
      its altered chemical structure, azithromycin is characterized by a broader
      spectrum of activity, lower incidence of adverse events and drug interactions and
      a pharmacokinetic profile, that is in contrast to existing macrolides. Because of
      its high and prolonged cellular and tissue concentrations, patients are able to
      complete a course of azithromycin within a shorter timeframe as compared to other
      antibiotics. Azithromycin is widely used in the treatment of adult and pediatric
      respiratory tract infections. Continued research into azithromycin's utility has
      resulted in indication development for several devastating infections such as
      trachoma. Large-scale studies of its activity against Chlamydia pneumoniae
      related atherosclerosis are underway.

PMID- 11296413
TI  - The anti-inflammatory effects of macrolides in cystic fibrosis.

PMID- 11296414
TI  - [New subjects for exceeding conventional on-pump CABG].
AB  - Coronary artery bypass grafting (CABG) used to be performed under cardiac arrest
      and cardiopulmonary bypass (CPB). During the last decade, efforts were made to
      minimize CPB-related complications. The technique of off-pump CABG (OPCAB) has
      been established during the last 5 years. Elimination of CPB and OPCAB has
      successfully reduced a number of perioperative complications and has provided
      early patient recovery. A compression type of coronary stabilizer was used early
      phase of OPCAB. Off-pump revascularization using the compression device was
      limited to the anterior wall of the heart. Bypass to the posterior wall under a
      beating heart was not popular until the suction type of stabilizer had become
      available. A suction device assisted by the Lima's pericardial suture allowed us
      to perform bypass grafting any aspects of the heart. Recently, we are
      skeltonizing the arterial grafts using the Harmonic scalpel. Applying
      skeltonizing technique to the radial artery or internal thoracic artery, we can
      successfully perform sequential grafting in selected cases. The number of distal
      anastomoses has been gradually increased as the device and technique were
      advanced (2.1 distal anastomoses with a compression device, 2.9 with a suction
      device, and 3.2 with the skeltonization technique). The frequency of the complete
      revascularization also increased. On the other hand, the complications associated
      with the procedure were comparable among these three off-pump methods, but were
      significantly fewer than on-pump CABG. Currently performed OPCAB can provide
      almost same number of distal anastomoses as on-pump CABG, with less frequency of
      postoperative mortality and morbidity, and with early patient recovery. These
      favorable results were attributed to the progress of the device and technique.

PMID- 11296415
TI  - [Off-pump coronary artery bypass grafting: comparison between standard CABG and
      off-pump CABG].
AB  - We have performed 321 cases of coronary artery bypass grafting (CABG), between
      October 15 1995 and November 20 2000. We have evaluated the operative results of
      142 cases (44.2%) of conventional CABG and 179 cases (55.8%) of off-pump CABG
      performed during this period. The average numbers of bypassed grafts was 3.53 for
      conventional CABG, and 1.62 for off-pump CABG. The total number of 369 grafts
      were anastomosed to 501 coronary arteries for conventional CABG, and 283 grafts
      were anastomosed to 290 coronary arteries for off-pump CABG. RESULTS: Although
      two saphenous veins were occluded, the early postoperative patency rate was 100%
      for conventional CABG using RITA, LITA, GEA and RA. Three site of stenosis in 18
      LITAs and 2 in 16 RITAs were recognized in off-pump CABG without the use of
      stabilizers. One site of stenosis in 130 LITAs and 3 string signs in 44 GEA were
      recognized in off-pump CABG with the use of stabilizers. Postoperative
      angiography in 52 off-pump CABG cases at one year later showed no new lesion.
      CONCLUSION: The use of stabilizers and LIMA suture enables adaptation of the
      MIDCAB procedure to a wider range of coronary artery bypass procedures, and a
      higher graft patency can be expected.

PMID- 11296416
TI  - [Evaluation of cases of off-pump CABG with mid-sternotomy].
AB  - Off-pump CABG was utilized on patients who had multivessel coronary artery
      disease and other organ diseases. A total of 79 patients who underwent off-pump
      CABG were evaluated. Of these, 66 suffered from OMI and AP, 4 form AP, 6 from u
      AP, and 3 from AMI. LITA was used in 75 cases, RA in 48, GEA in 45, RITA in 13,
      IEA in 3, and SVG in 38. Revascularization was performed at # 2 in 3 cases, # 3
      in 11, 4 PD in 37, 4 PL in # 7 or # 8 in 79, # 9 in 27, # 12 in 51, and # 14 in
      17. A time of 10.3 min was spent on LAD revascularization, 9.8 min on D 1, 10.2
      min on Cx, anf 11.5 on RCA. Seven patients were transferred to on-pump beating
      CABG because of hemodynamic instability. One patients suffered postoperative CVA,
      and 2 had wound infection. Complete revasculization was accomplished in 78
      patients, and hospital death was not reported.

PMID- 11296417
TI  - [Partial sternotomy for off-pump coronary artery bypass grafting].
AB  - We performed off-pump coronary artery bypass grafting through a partial
      sternotomy. The sternum was spit like C-shape configuration from the second
      intercostal space down to the xiphoid junction. The left internal mammary
      arteries were mobilized and anastomosed to the left anterior descending arteries.
      Saphenous veins were grafted between the ascending aorta and the right coronary
      arteries or diagonal branches. After the surgery, excellent stability of the
      thorax with minimized incisions enhanced the early recovery. We believe that
      partial sternotomy approach may be useful in some cases of off-pump CABG.

PMID- 11296418
TI  - [Lower-end sternal splitting (LESS) approach as a new strategy for minimally
      invasive off-pump CABG].
AB  - There are several ways to perform off-pump coronary artery bypass grafting
      (OPCAB) using a minimally invasive method. Currently, one of the most commonly
      used approaches is left anterior small thoracotomy (LAST). However, using this
      approach, only the LAD can be grafted. We have employed a partial sternotomy
      without a transverse cut, namely, the lower-end sternal splitting (LESS) approach
      for OPCAB. Through this approach, the LAD and RCA can be revascularized via a
      single small incision without the risk of damaging the tissue around the
      intercostal space when the sternum is transversely divided. Since November 1999
      to September 2000, we have applied OPCAB through LESS approach in 17 patients.
      Mean age was 70.0 + 5.4 years (range 58-77), and 13 were men. Mean length of the
      skin incision was 8.6 + 1.2 cm (range 8-11). No hospital death or morbidity was
      observed. No patient required blood transfusion. All had arterial conduits: LITA
      LAD, in 11; LITA-LAD, RITA-RCA, in 1; LITA-LAD, GEA-PDA, in 2; LITA-LAD, RITA
      RCA, RITA-RA-PDA, in 1; and GEA-PDA, in 2. All underwent postoperative coronary
      angiography, and the patency rate was 95.5%. Our experience demonstrates that the
      LESS approach for OPCAB is technically feasible and can be used with excellent
      cosmetic results and safety. Although experience is limited, this less invasive
      surgical technique can be used as an alternative approach for MIDCAB in patients
      with LAD and/or RCA disease.

PMID- 11296419
TI  - [Minimally invasive direct coronary artery bypass performed via diaphragmatic
      approach].
AB  - From October 1996 until August 2000, coronary artery bypass grafting (CABG) for
      right coronary artery was performed via diaphragmatic approach. This procedure
      was done in 18 patients consist of 13 male and 5 female ranging in age from 47 to
      81 years old. Ten of 18 cases were performed coronary bypass reoperation. Right
      gastroepiploic artery was used in 16 cases, and branched radial artery or
      saphenous vein graft from gastroduodenal artery was used in one case. Bypassed
      region in right coronary artery was segment 3 in 9 cases, right posterior
      descending artery in 8 and right atrio-ventricular branch in one. All grafts were
      patent in postoperative cardiac catheterization. This approach was desirable for
      the case, which bypass grafting to right coronary artery is necessary, on account
      of avoiding injury of patent bypassed graft by median sternotomy in re-do CABG.
      For the patient whose stomach had been resected, bypass grafting from
      gastroduodenal artery with radial artery or saphenous vein graft to right
      coronary artery is useful procedure.

PMID- 11296420
TI  - [Early results and new indication of the off-pump coronary artery bypass
      (OPCAB)].
AB  - BACKGROUND: The off-Pump coronary artery bypass (OPCAB) has recently gained
      popularity. However the safety and feasibility of the procedure has not been
      fully proven especially for unstable myocardial ischemia. METHODS: Between March
      1998 and November 2000, 135 patients with a mean age of 69.7 (41-95) underwent
      off-pump coronary artery bypass via sternotomy. Eight patients were operated on
      emergently and 11 were urgently. LV function ranged from 8% to 70%. Eleven
      patients required preoperative IABP. RESULTS: All procedures were completed
      without conversion to cardiopulmonary bypass. The mean number of grafts per
      patient was 2.8 (range, 1 to 6). Cardiac-related hospital mortality was 2.2%
      (3/135). Angiographic assessment of grafts demonstrated an overall patency of
      98.0%, arterial grafts 98.7% and venous grafts 96.6%. In retrospect, these were
      equivalent results of conventional coronary artery bypass by the same operator.
      CONCLUSION: OPCAB is safe and feasible even with LV dysfunction or unstable
      myocardial ischemia.

PMID- 11296421
TI  - [Evaluation of value of coronary artery bypass grafting without cardiopulmonary
      bypass for emergency or subemergency case].
AB  - From August 1999 through September 2000, emergency (operation within 24 hours
      after hospitalization) or subemergency (within 48 hours) coronary artery bypass
      grafting without cardiopulmonary bypass (OPCAB) was performed in 16 patients (EM
      group) with a mean age 71.9 years old (range: 47-85). The patients were divided
      into 3 groups of which were acute myocardial infarction (AMI) group, chronic
      heart failure (CHF) group and unstable angina (u-AP) group, and compared
      preoperative hemodynamics, the number of graft, target arteries, bypass patency
      and hospitalization period after surgery with 26 patients performed the elective
      OPCAB in the same duration (EL group). All patients in EM group were used intra
      aortic balloon pumping (IABP) assist before operation. In EL group, 16 patients
      (61.5%) were required IABP (p < 0.05). Ejection fraction and cardiac index in CHF
      group were significantly lower than those of EL group (47.8 +/- 1.1 vs. 63.3 +/-
      2.4, 2.8 +/- 0.2 vs. 1.9 +/- 0.2: p < 0.05). Pulmonary capillary wedge pressure
      in AMI group and CHF group was significantly higher than that of EL group (16.7
      +/- 5.9, 20.8 +/- 5.4 vs. 7.2 +/- 0.8: p < 0.01). There was a significant
      difference in the mean number of bypass in EM group compared with that of EL
      group (1.8 +/- 0.2 vs. 2.7 +/- 0.2: p < 0.05). In AMI group and CHF group, the
      grafting rate to the major vessel in the anterior wall was occupied in more than
      70% of all bypasses per patient, however that was less than 50% in EL group. The
      arterial graft was actively used for revascularization. The hospitalization
      period in AMI group and CHF group was longer than that in u-AP group and EL group
      (28.5 +/- 9.8, 38.8 +/- 7.4 vs. 15.7 +/- 1.5, 13.0 +/- 0.7: p < 0.01). There was
      no difference in bypass patency between EM group and EL group (96.6 vs. 97.2).
      During the follow-up period, any death and complications were not recognized in
      both groups. These results suggested that OPCAB would be one of the valuable
      procedures in the emergent coronary artery bypass grafting.

PMID- 11296422
TI  - [Simultaneous surgery for unstable angina and gastric cancer: a case report].
AB  - This report describes a case in which an 81-year-old male underwent two
      operations simultaneously for unstable angina and gastric cancer. Successfully
      performed procedures were off pump CABG with bilateral IMA, and total
      gastrectomy. The post operative course was uneventful. Off pump CABG is an
      effective procedure in patient with malignant neoplasm.

PMID- 11296423
TI  - [Is routine application of off-pump coronary artery bypass grafting warranted?].
AB  - The limitation and indication of off-pump coronary artery bypass grafting (OPCAB)
      remain controversial. Since May 1999, we have applied OPCAB for all isolated
      coronary bypass cases routinely. Intraoperative conversion to CCAB occurred in 8
      patients (10.8%). The main reasons for conversion were intramyocardial coronary
      arteries and arythmia-induced hemodynamic instability in the acute phase of
      myocardial infarction. We evaluated the results of OPCAB as compared to
      conventional coronary artery bypass (CCAB) as a historical control. The operative
      mortality was 1.6% in both groups. Postoperative complications including renal
      failure and requirements of circulatory support were significantly less in OPCAB.
      Postoperative max CPK-MB value, the amount of postoperative bleeding and the
      requirement of transfusion were also significantly less in OPCAB. Only
      neurological complication in OPCAB was temporary delirium in a high-aged patient,
      whereas three patients developed neurological complications including permanent
      stroke in CCAB. Right heart bypass was effectively utilized to maintain
      hemodynamics and expose the posterior vessels in patients with severely dilated
      and poorly functioning left ventricle (EF: 24-31%) and a patient with multiple
      severe stenosis in cerebral arteries. Coronary angiogram performed after the
      operation demonstrated 94% of graft patency. These results warrant the further
      application of OPCAB for multivessel surgical revascularization.

PMID- 11296424
TI  - [Usefulness of OPCAB from the viewpoint of fluctuations in the level of blood
      natriuretic peptides].
AB  - Fluctuations in the level of blood natriuretic peptides (ANP and BNP) were
      compared between 41 patients who underwent conventional coronary artery bypass
      (CCAB) and 19 patients who underwent off-pump coronary artery bypass (OPCAB). A
      blood sample was collected before surgery, and 6, 12 and 24 hours; 2, 3, 5 and 7
      days; and 1 month after the end of extracorporeal circulation. There were no
      significant differences in left ventricular ejection fraction (LVEF) before and
      after surgery in either group or between the two groups. On average, 3.3 +/- 1.0
      bypass grafts were used for the CCAB group, and 2.2 +/- 0.8 grafts for the OPCAB
      group. Furthermore, the maximum postoperative creatine phosphokinase-MB (CK-MB)
      level for the CCAB group was 49.1 +/- 17.5 IU/l, whereas that for the OPCAB group
      was significantly lower at 23.2 +/- 24.8 IU/l. The preoperative level of blood
      ANP for the CCAB group was 24.6 +/- 19.9 pg/ml while that for the OPCAB group was
      39.3 +/- 29.5 pg/ml, but there was no significant difference between the two
      groups. In both groups, the level of blood ANP reached a peak three days after
      the end of extracorporeal circulation and then decreased after that point.
      Although the level of blood ANP for the OPCAB group decreased to 51.4 +/- 26.4
      pg/ml one month after the end of extracorporeal circulation, that for the CCAB
      group one month after the end of extracorporeal circulation remained
      significantly high at 61.3 +/- 30.6 pg/ml, when compared to that before surgery.
      Furthermore, the preoperative level of blood BNP for the CCAB group was 40.0 +/-
      35.2 pg/ml and that for the OPCAB group was 75.5 +/- 59.7 pg/ml, but there was no
      significant difference between the two groups. Then, in both groups, the level of
      blood BNP reached a peak 2-5 days after the end of extracorporeal circulation and
      then decreased after that. Whereas the level of blood BNP for the OPCAB group
      decreased to 96.4 +/- 56.0 pg/ml one month after the end of extracorporeal
      circulation, that for the CCAB group one month after the end of extracorporeal
      circulation remained significantly high at 160.3 +/- 106.2 pg/ml when compared to
      that before surgery. The levels of ANP and BNP increased postoperatively for both
      OPCAB and CCAB groups since the following events caused a great degree of stress
      on the heart: general anesthesia, cardiac herniation, stabilizer compression,
      regional blood flow blockage and reperfusion injury. Although the level of
      natriuretic peptides for the CCAB group remained high one month after the end of
      surgical stress, that for the OPCAB group returned to near the preoperative level
      one month later, thus supporting the notion that OPCAB is less invasive.

PMID- 11296425
TI  - [The role of ischemic preconditioning in off-pump CABG: is it really necessary to
      accomplish scrupulous ischemic preconditioning?].
AB  - In an attempt to avoid the deleterious effect of cardiopulmonary bypass, off-pump
      coronary artery bypass grafting has been rediscovered and spread. We often
      accomplish the ischemic preconditioning (IP) in off-pump CABG. IP is the
      phenomenon in which sublethal episode of myocardial ischemia result in increased
      tolerance to a later, potentially lethal, episode of ischemia. To evaluate the
      cardioprotective effect of IP and an ATP-sensitive potassium channel (KATP)
      opener, oxidative radical scavenger, 43 clinical cases were examined. The
      myocardial tissue oxygen saturation was measured by near-infra red spectroscopy
      during IP. Twelve cases were subjected to accomplish simple IP (5 min x twice),
      and 29 cases received pharmacological IP (administrated allopurinol
      preoperatively and nicorandil intraoperatively; 3 min x once). The result showed
      that the tissue oxygen of pharmacological IP group is superior to that of simple
      IP group. The concomitant use of IP and KATP opener, oxidative radical scavenger
      both ameliorated cardiac dysfunction during the ischemia in anastomotic occlusion
      of the coronary artery, and improved the postischemic functional recovery. These
      results suggest that we would be able to decrease both duration and the number of
      times of IP by using KATP opener and oxidative radical scavenger.

PMID- 11296426
TI  - [The usefulness of intra-operative angiography during off-pump CABG].
AB  - BACKGROUND: Recently OPCAB has become more and more common in CABG, although one
      problem of OPCAB like the quality of anastomosis has not been solved yet. We
      discussed the usefulness of intra-operative angiography during OPCAB. METHODS:
      During March 1997-July 2000, 55 patients underwent OPCAB (including 35 MIDCAB
      cases) in our institute. Graft flow and anastomosis were examined by intra
      operative or immediate post-operative angiography. RESULTS: Immediate
      postoperative angiography was performed in 22 MIDCAB cases. In 15 cases an
      excellent graft flow without stenosis could be confirmed, in 7 cases the native
      LAD was so small, which caused a poor flow of the LITA and three cases needed
      additional PTCA because of anastomosis stenosis. Intra-operative angiography was
      done in 9 MIDCAB and 17 OPCAB. As a result, re-anastomosis was performed in one
      case of MIDCAB because of severe anastomosis stenosis, one case of OPCAB had
      confirmed poor flow because of a small LAD, but in 24 cases an excellent graft
      flow could be seen on time. In 2 cases OPCAB was combined with PTCA to achieve
      complete revascularization. CONCLUSIONS: Intra-operative angiography is a useful
      strategy to confirm the surgical results quickly in OPCAB (included MIDCAB).
      Using such a strategy, combination of OPCAB and PTCA as a new approach for
      complete revascularization can be performed safe and smooth.

PMID- 11296427
TI  - [Pitfall in the choice of the in situ arterial grafts in OPCAB].
AB  - Flow capacity with arterial grafts which have been used in off-pump CABG has been
      discussed. To analyze the hypoperfusion syndrome when in situ arterial grafts are
      selected, we made the simple mathematical model which consisted of two vessels
      with in parallel. We speculated the flow capacity of the various grafts, and flow
      distribution in the distal coronary artery, based on Poiseuille's law. This
      theoretical model clearly demonstrated that hypoperfusion syndrome occurred in
      reoperative coronary bypass grafting had a close relation with the diameters and
      lengths of bypass grafts.

PMID- 11296428
TI  - [Off-pump coronary artery bypass using bilateral in situ internal thoracic artery
      grafts for left coronary artery system: a case report].
AB  - A 63-year-old man with triple vessel disease in the coronary artery and multiple
      arterial stenoses in intra-cranial vessels underwent off-pump coronary artery
      bypass (OPCAB). We were able to perform three coronary artery bypass grafting (in
      situ left internal thoracic artery (left ITA)--left anterior descending artery,
      in situ right ITA--circumflex artery through the transverse sinus, and saphenous
      vein graft--right coronary artery) using octopus 2 and "Lima" suture technique
      without cardio-pulmonary bypass. Operation time was 355 minutes and established
      blood loss was 440 ml. Postoperative course was uneventful. Postoperative
      angiogram revealed well patent three grafts. Using bilateral in situ ITAs OPCAB
      could achieve high quality.

PMID- 11296429
TI  - [A resected case of multiple lung cancers].
AB  - A 78-year-old man was admitted to our hospital because of abnormal shadows on
      chest film. A 20 x 25 mm tumor shadow was found in the right lower lung field
      (S10) and a 5 x 10 mm tumor shadow in the right upper lung field (S2).
      Bronchoscopic curettage revealed squamous cell carcinoma from the specimen on the
      S10 and did not revealed malignant cells from the specimen on the S2. He was
      performed operation, squamous cell carcinoma in the S10 was removed by right
      lower lobectomy and nodule in the S2 was also removed by partial resection.
      Histological examination confirmed well-differentiated squamous cell carcinoma
      from the S10 and well-differentiated adenocarcinoma from the S2. He is healthy
      three year after operation.

PMID- 11296430
TI  - [Aortic dissection in aged siblings without Marfan's syndrome].
AB  - Aortic dissection rarely occurs in 2 or more family members without Marfan's
      syndrome. This report describes two aged siblings who underwent emergency
      operations for aortic dissection. Case 1: A 71-year-old female (sister), who had
      Stanford type B aortic dissection, underwent replacement of the descending aorta
      with a Hemashield graft. Case 2: A 72-year-old male (brother of case 1), who had
      Stanford type A aortic dissection, underwent replacement of the ascending aorta
      with a UBE graft following the closure of the entry located in the proximal arch.
      Neither of 2 siblings nor other family members had any features of the Marfan's
      syndrome. It is proposed that two aortic dissections occurred coincidentally in
      one family without Marfan's syndrome.

PMID- 11296431
TI  - [A frequent fiber-scopic bronchial lavege for the case of bilateral sever
      pulmonary contusion with flail chest].
AB  - A 26-year-old man was injured in the traffic accident. He had complicated chest
      trauma. He came to our hospital by ambulance immediately after rescued from
      crashed his automobile. He had severe pulmonary contusion with frail chest,
      pulmonary laceration, tension hemopneumothorax, and hypovolemic shock, and air
      embolism of the brain. He was managed with fiber-optic bronchoscopy under
      mechanical ventilation and chest drainage. Frequent broncho-scopic bronchial
      lavage of respiratory tract with thrombin and adrenaline solution was helpful to
      prevent anoxia due to complicated chest injury. He developed acute bacterial
      empyema and multiple organ failure due to septic shock during intensive care for
      trauma. However, he underwent surgical treatment for empyema and fully returned
      to his work after 6 months after his critical accident.

PMID- 11296432
TI  - [Assessment of anesthesia satisfaction using direct interviews at post-anesthesia
      clinic].
AB  - The authors studied 5,034 consecutive patients undergoing elective surgery.
      Preoperative, intraoperative, and postoperative variables were gathered and
      patient satisfaction was assessed using direct interviews at pre- and post
      anesthesia clinic. Fifty-nine percent of the 4,717 responders showed satisfaction
      and 4% showed dissatisfaction with anesthesia. The most undesirable perioperative
      outcome was vomiting/nausea. Other undesirable outcomes include discomfort of
      urine catheter, sore throat, memory of extubation, postoperative pain and so on.
      Anesthesiologist can improve the quality of anesthesia by preoperative
      explanation and preventative management for undesirable perioperative outcomes.

PMID- 11296433
TI  - [Blood concentrations and side effects of tacrolimus in a living renal
      transplantation].
AB  - In a living renal transplantation, the recipients are administered an
      immunosuppressive agent preoperatively. The drug exhibits a high incidence of
      side effects of special note. We examined the side effects of tacrolimus to
      evaluate the postoperative management of living renal transplantation.
      Hypertension, hyperglycemia, tachycardia and chest pain were found as the side
      effects. The blood concentration should be measured frequently to maintain the
      effective blood concentration and to prevent the side effect.

PMID- 11296434
TI  - [The effect of continuous intra-articular and intra-bursal infusion of lidocaine
      on postoperative pain following shoulder arthroscopic surgery].
AB  - We evaluated the effects of continuous intra-articular and intra-bursal infusion
      of lidocaine on postoperative pain following shoulder arthroscopic surgery. Forty
      one ASA I-II patients scheduled for shoulder arthroscopic surgery, were allocated
      into following four groups. The patients, after intra-articular arthroscopic
      surgery, either received intra-articular lidocaine (Group I, n = 10) or did not
      (Group III, n = 10). The patients after extra-articular arthroscopic surgery
      either received intra-bursal lidocaine (Group II, n = 11) or did not (Group IV, n
      = 10). Group I and Group II received 8 ml of 1% lidocaine intra-articularly and
      intra-bursally, respectively, at the end of surgery, followed by continuous
      infusion of 1% lidocaine at the rate of 2 ml.hr-1 for 24 hours. The intensities
      of postoperative pain were evaluated by Visual Analogue Scale (VAS), 2, 5, 8, 12,
      18 and 24 hours after surgery, and by the number of patients' request for
      supplemental analgesic for 24 hours. The VAS scores and the number of analgesic
      requests were significantly lower (P < 0.05) in Group I than Group III, and in
      Group II than Group IV throughout the postoperative observation period. No
      adverse effects were observed during this study. We conclude that continuous
      intra-articular and intra-bursal infusion of lidocaine provides effective
      postoperative pain relief for shoulder arthroscopic surgery.

PMID- 11296435
TI  - [Dose-response study of preincisional buprenorphine on emergence time and
      postoperative analgesic requirement in patients anesthetized with sevoflurane].
AB  - The effect of intravenous buprenorphine on emergence time from sevoflurane
      anesthesia and postoperative analgesic requirement was evaluated after
      otolaryngeal surgeries. Forty-five patients were randomly assigned to one of
      three treatment groups (n = 15 each): Control-group received saline as a control;
      2 micrograms-group received buprenorphine 2 micrograms.kg-1; and 4 micrograms
      group received buprenorphine 4 micrograms.kg-1, respectively. Study drug was
      administered intravenously at the induction of general anesthesia. Anesthesia was
      maintained with sevoflurane (1.5%) and nitrous oxide (66%) in oxygen. The pain
      score, postoperative analgesic requirement, and incidence of nausea and/or
      vomiting were examined. The emergence times were 16.4 +/- 3.5, 14.7 +/- 5.2, and
      17.8 +/- 7.7 min [mean +/- SD], in the control-group, the 2 micrograms-group, and
      the 4 micrograms-group, respectively. There were no differences among the groups
      in term of the end-tidal sevoflurane concentration immediately before tracheal
      extubation. In the control-group, the 2 micrograms-group, and the 4 micrograms
      group, 10, 1, and 3 patients, requested additional analgesics during the first 24
      hours after surgery, respectively (control-group vs. 2 micrograms-group and 4
      micrograms-group, P < 0.05). Nausea and vomiting occurred more frequently in the
      2 micrograms-group and the 4 micrograms-group. We conclude that buprenorphine (2
      or 4 micrograms.kg-1) reduced analgesic requirement during the first 24 hours
      after surgery without delaying emergence from sevoflurane anesthesia.

PMID- 11296436
TI  - [Evaluation of emergence from total intravenous anesthesia with propofol for long
      neurosurgery].
AB  - In six neurosurgical patients we examined their emergence from more than six
      hours of total intravenous anesthesia with propofol and fentanyl. The anesthesia
      was maintained properly with total intravenous anesthesia with propofol and
      fentanyl without nitrous oxide. We calculated the estimated blood concentration
      of propofol from the anesthesia record using a three-compartment pharmacokinetic
      model. The patients were extubated after they had shown good awareness. The
      average time for extubation was 18 minutes after discontinuation of propofol
      infusion. The mean estimated concentration of propofol at the extubation was 1.36
      micrograms.ml-1 (range: 1.1-1.5 micrograms.ml-1). The estimated emergence times
      in these cases, also calculated with the pharmacokinetic model, correlated
      significantly with the time from discontinuation of propofol infusion to the
      patients' awakening. It was concluded, first, that the estimated concentration of
      propofol at extubation after long anesthesia was similar to that measured in
      common cases, and second, that we could reduce the emergence time at the tail end
      of long-sustained neurosurgery by avoiding the delay in emergence.

PMID- 11296437
TI  - [Electroencephalographic characteristics during maintenance and emergence from
      propofol-ketamine-fentanyl anesthesia].
AB  - Spectral edge frequency 90 (SEF 90) and relative power in four frequency bands
      (beta, alpha, theta, delta) of the processed electroencephalogram were recorded
      in 20 patients undergoing elective gynecological surgery under total intravenous
      anesthesia (propofol-ketamine-fentanyl) (group PKF, n = 10) or nitrous oxide
      oxygen-isoflurane (group GOI, n = 10) anesthesia. During anesthesia, mean SEF 90
      and relative beta power increased more significantly in group PKF than in group
      GOI. At emergence from anesthesia, SEF 90 was 21.8 Hz in group PKF and 20.5 Hz in
      group GOI. These results suggest that it is difficult to evaluate the depth of
      anesthesia using pEEG under PKF anesthesia.

PMID- 11296438
TI  - [Light-wand (Trachlight) guided nasotracheal intubation].
AB  - We report that Trachlight-guided nasotracheal intubation might be achieved
      successfully and traumatically without removal of a stiff internal stylet.
      Endotracheal tube was mounted on a Trachlight with the stylet in position and
      bent to form a less sharp curvature than a right angle, namely 40-60 degree, at 7
      cm proximal to the endotracheal tube tip. Forty-six patients scheduled for nasal
      intubation were studied to measure the intubation time and the success rate with
      the use of Trachlight. The tracheas were successfully intubated in 89% of
      patients. We suggest that Trachlight-guided nasotracheal intubation could be
      clinically feasible without traumatic complication when applied with a stiff
      stylet in position and this approach is a useful method for nasal intubation.

PMID- 11296439
TI  - [Total intravenous anesthesia by propofol, fentanyl and ketamine for five cases
      of acute superior mesenteric artery occlusion].
AB  - We report the anesthetic management for emergency surgery of five patients with
      acute superior mesenteric artery occlusion. Although induction was performed with
      a combination of propofol, fentanyl and ketamine, their hemodynamics was
      relatively stable during the induction and maintenance of anesthesia. Immediately
      after embolectomy, reperfusion of the superior mesenteric artery led to sudden
      hypotension, requiring the administration of fluids and vasoactive agents in two
      of four patients. Unfortunately, two of the five patients died of cardiac arrest
      and multiple organ failure in the early postoperative period. While total
      intravenous anesthesia with propofol, fentanyl and ketamine may provide stable
      anesthetic management in patients with superior mesenteric artery occlusion, it
      must be emphasized that in addition to careful intraoperative management, such
      patients require intensive and multiple organ care during the postoperative
      period.

PMID- 11296440
TI  - [A case of wide-spread emphysema following the extraction of mandibular third
      molar under intravenous sedation].
AB  - A 45 year-old male underwent lower left third molar extraction under intravenous
      sedation. During the surgical extraction of the mandibular left impacted third
      molar using a high-speed air-turbine drill, the patient complained of compression
      at the level of the right breast without any abnormal vital signs. Radiological
      investigation and CT scan showed a picture of bilateral, subcutaneous and
      mediastinal emphysema involving the bilateral face, neck and pectoral area.
      Following the antibiotic therapy, the drainage was performed through bilateral
      pectoral incisions by thoracic surgery. The patient recovered within two days and
      underwent the completion of this surgery under general anesthesia one month
      later.

PMID- 11296441
TI  - [Anesthetic management of a patient with gunshot injury in the neck and the
      chest].
AB  - We present a case of a 27-year-old man with gunshot injury in the neck and the
      chest. On admission, he had an entry wound in the neck and his chest radiograph
      showed left hemopneumothorax. Nasal endotracheal intubation and chest drainage
      were immediately performed. Angiography revealed pseudoaneurysm of the left
      carotid artery and fistula between the artery and the innominate vein. The
      patient showed progressive severe facial edema due to the fistula. Anesthesia was
      induced and maintained with fentanyl and sevoflurane. The carotid artery was
      repaired with an autologous saphenous vein graft. Although one lung ventilation
      (OLV) was requested for partial resection of the left lung, replacing the
      endotracheal tube was impossible due to severe facial edema. OLV was successfully
      performed by blocking the left main trunchus with a 7 Fr Fogarty catheter placed
      under fiberscopic monitoring. The patient recovered without any serious
      complications. Prompt and proper airway management is required in gun shot injury
      of the neck and chest.

PMID- 11296442
TI  - [Estimation of size of the uncuffed endotracheal tube for pediatric cardiac
      anesthesia--Cole's formula cannot estimate the appropriate tube size].
AB  - We evaluated the validity of Cole's formula (tube size = 0.25 x age + 4) for the
      estimation of uncuffed endotracheal tube size, and devised new formula with a
      statistical method on the basis of the ages of 217 pediatric patients with
      congenital heart disease. The sizes of the tubes actually used for these patients
      were 0.5 mm or larger than those estimated by Cole's formula in 29% of patients
      with congenital heart disease. Only one patient with cyanotic heart disease
      required a tube that was more than 0.5 mm smaller than that estimated by Cole's
      formula. The regression formula representing the relationship between the tube
      size and age was "tube size = 0.316 x age + 4.135". In conclusion, tube size
      estimated by Cole's formula tends to be smaller than practically appropriate tube
      size for pediatric cardiac anesthesia, and therefore we suggest new formula to
      estimate the tube size.

PMID- 11296443
TI  - [Perioperative management of a child with congenital nephrogenic diabetes
      insipidus].
AB  - The key point in perioperative management of a patient with congenital
      nephrogenic diabetes insipidus is fluid and electrolytes management. Since the
      urine of these patients consists mainly of solute free water, replacement fluids
      should be fluids which provide free water. A 2-year-old girl with congenital
      nephrogenic diabetes insipidus was scheduled for dental extraction. Her daily
      fluid intake was 10 liter. She had a history of recurrent fever, polyuria and
      polydipsia since 2 months of age. Her previous perioperative course for gastric
      volvulus at another hospital was complicated with postoperative hyponatremia and
      convulsion. A venous line was secured the day before surgery and 5% dextrose in
      water was infused at a rate of 12 ml.kg-1.hr-1. Intraoperative infusion was
      mainly with 5% dextrose in water combined with maintenance fluid. Five hours
      after surgery oral intake was started. Her intraoperative electrolytes levels
      were low (Na 133 mEq.l-1, K 2.8 mEq.l-1), but otherwise her perioperative course
      was uneventful.

PMID- 11296444
TI  - [Epidural anesthesia for a patient with catamenial pneumothorax].
AB  - Endometriosis extending into the thoracic cage or the lung might induce defect of
      the tissue and show catamenial symptoms, such as pneumothorax or hemothorax.
      These events usually occur 48 to 72 hours after menstruation. A 37-year-old woman
      with ten year history of recurrent catamenial pneumothorax was scheduled for
      removal of ovarian cyst. Since intermittent positive pressure ventilation or
      pneumoperitoneum might induce pneumothorax, we selected epidural anesthesia for
      laparotomy. Epidural cannulations were performed at Th 9/10 and L 4/5
      interspaces. After administration of 2% mepivacaine (400 mg) and fentanyl (0.1
      mg), the block extended from Th 6 to S 5. The surgery was done without any
      complication. In this case epidural anesthesia for laparotomy was useful for the
      patient with catamenial pneumothorax.

PMID- 11296445
TI  - [A case of pulmonary embolism associated with pneumatic tourniquet deflation].
AB  - Intraoperative pulmonary embolism is an unusual complication of lower extremity
      surgeries. We report a case of cardiac arrest due to pulmonary embolism
      associated with pneumatic tourniquet deflation. A 48-yr-old woman underwent
      achillorrhaphy under spinal anesthesia. About 4 min after deflation of the
      tourniquet, cyanosis appeared, and her consciousness was lost. Endotracheal
      intubation was performed, and ephedrine and epinephrine were injected
      intravenously. Right ventricular dilation was noted in echocardiography, although
      left ventricular contractility was intact. Multiple emboli were observed in the
      bilateral main pulmonary arteries in pulmonary angiography. Despite
      administration of thirty six million units of tissue plasminogen activator, her
      pulmonary blood flow was not restored.

PMID- 11296446
TI  - [Combination of acute normovolemic hemodilution technique with preoperative
      autologous blood donation prevented allogeneic blood transfusion against 4000 g
      surgical blood loss in a patient undergoing left partial nephrectomy].
AB  - A 41-year-old male patient with well-controlled hypertension underwent a partial
      nephrectomy under total intravenous anesthesia with propofol, fentanyl and
      ketamine. To avoid allogeneic blood transfusion, preoperative autologous blood
      donation (400 g) a week before the surgery and acute normovolemic hemodilution
      (800 g) after induction of anesthesia were performed. As surgical blood loss was
      more than 4000 g, blood hemoglobin (Hb) level decreased to 6.4 g.dl-1. However,
      as intraoperative hemodynamics was relatively stable with no ischemic changes in
      ECG and arterial blood gas analysis did not show metabolic acidosis, autologous
      blood transfusion was withheld till hemostasis had been done. After returning the
      autologous blood, Hb increased to 9.4 g.dl-1. On the 2nd postoperative day, Hb
      decreased to 7.6 g.dl-1. As the patient's vital signs did not show any severe
      complications, blood transfusion was not performed. Then, the Hb level increased
      gradually to 13.9 g.dl-1, 3 month later without allogenic blood transfusion. In
      addition, any postoperative complications by low Hb level were not recognized so
      far. This case suggests that combination of autologous transfusion techniques may
      be effective to avoid allogeneic blood transfusion even against massive
      hemorrhage. However, to avoid disadvantage of these technique, we should always
      evaluate preoperative patient conditions.

PMID- 11296447
TI  - [Perioperative administration of bicarbonated solution to a patient with
      mitochondrial encephalomyopathy].
AB  - A 16-year-old man with mitochondrial encephalomyopathy underwent biopsy and
      nephrectomy under general anesthesia. Mitochondrial encephalomyopathy is caused
      by mitochondrial dysfunction, and frequently accompanies elevation of lactic and
      pyruvic acid levels in the blood. It has been considered that problems of
      anesthesia for the patient with mitochondrial encephalomyopathy are the
      probability of hyperlactacidemia, the relevance to malignant hyperthermia, the
      possibility of myocardial disease and dysfunction of heart conduction system,
      respiratory depression due to muscle weakness, and so on. Therefore, to prevent
      hyperlactacidemia, we prepared the extracellular fluid solution including
      bicarbonic acid but no lactic and acetic acid, and infused the solution to the
      patient during anesthesia. By use of this solution, his lactic acid level was
      kept within the normal range during anesthesia and no metabolic acidosis
      occurred. His hemodynamics was stable and he showed normal response to
      vecuronium, recovering from anesthesia smoothly and postoperative course was
      uneventful.

PMID- 11296448
TI  - [Pulmonary edema in a child following laryngospasm triggered by a laryngeal mask
      airway during emergence from anesthesia].
AB  - A 9-year-old boy underwent biopsy of the tumor at the external auditory meatus
      under general anesthesia with a laryngeal mask airway(LMA). During emergence from
      anesthesia, laryngospasm with marked inspiratory effort and cyanosis occurred.
      The LMA was removed and the patient was orotracheally intubated following
      vecuronium administration. In spite of controlled ventilation with 100% oxygen,
      oxygen saturation remained at low 90s and pink frothy sputum appeared in the
      tracheal tube. We suspected negative pressure pulmonary edema and treated him
      with mechanical ventilation with positive end-expiratory pressure. Seventeen
      hours later the pink frothy sputum decreased and he was extubated. Laryngospasm
      during emergence from anesthesia with an LMA can induce negative pressure
      pulmonary edema, especially in pediatric patients.

PMID- 11296449
TI  - [Evaluation of efficiency of ACD-CPR and STD-CPR; a multi-institutional study].
AB  - We compared the efficacy of ACD-CPR and STD-CPR based on 64 multi-institutional
      reports. No significant differences were observed in the rate of restoration of
      spontaneous circulation (ROSC) and in cardiopulmonary parameters during CPR using
      the two methods. There were 5 cases in which cardiopulmonary parameters improved
      after switching from STD-CPR to ACD-CPR and, eventually, in two of them
      spontaneous circulation was restored. In the ROSC cases of both groups, ETCO2 and
      values of SpO2, PaO2, and systolic BP at 30 minutes were higher than those of non
      ROSC cases. ETCO2 never exceeded 20 mmHg in the non-ROSC cases, but it was higher
      in the ROSC cases. ACD-CPR is a good choice when trained persons are present or
      when extra hands are available to continue the CPR.

PMID- 11296450
TI  - [A survey of 3,303 6th-year medical students from 36 universities concerning
      knowledge of resuscitation--more than 80% of medical students can not perform
      standard cardiopulmonary resuscitation?].
AB  - Questionnaires on knowledge of resuscitation were distributed to 3,303 6th-year
      medical school students from 36 universities. The questionnaire included 13
      questions based on the 1992 guidelines for cardiopulmonary resuscitation. From
      the 13 questions, each student was instructed to select 6 questions concerning
      assessment of consciousness level, method for confirming respiration, method for
      securing the airway, method for confirming circulation, pressure points for
      cardiac massage, and the ratio of respiration and cardiac massage. If all of
      these six questions could not be answered correctly, it was considered that the
      student was not able to perform resuscitation according to the guidelines. At
      least one incorrect answer was given to the six questions by 84% of students,
      indicating that most medical students are not able to actually perform standard
      resuscitation. Possible reasons for these results may be the lack of desire on
      the part of students to master resuscitation, confusion over new findings
      concerning resuscitation and guideline, insufficient understanding of the
      difference between the guidelines and new findings by educators, and restricted
      teaching time for resuscitation. Possible ways to improve the situation include
      efforts to make students more responsible to master resuscitation, efforts to
      enhance students' desire to learn, adoption of more practical education,
      inclusion of such questions in graduation examinations and the national
      examination for a medical license, adherence by educators to the guidelines, and
      efforts by educators to make a clear distinction between the guidelines and new
      findings. With new guidelines for cardiopulmonary resuscitation due out in the
      year 2000, methods for teaching resuscitation should be reconsidered in order to
      ensure that all medical students can competently perform resuscitation.

PMID- 11296451
TI  - [A questionnaire-based survey on the Internet concerning optimal timing for knee
      surgery in a patient with rheumatoid arthritis].
AB  - To investigate the differences between orthopedists and internists in indications
      for surgical management in patients with rheumatoid arthritis (RA), a
      questionnaire-based survey was performed on the Internet with the presentation of
      a case of progressive RA along with serial X-ray films of the knee. Ninety-three
      doctors (43 orthopedists and 50 internists, average age: 49.2 years) answered the
      questionnaire. Most of the doctors who viewed the X-ray film showing Larsen's
      grade IV chose that as the optimal time for total knee arthroplasty. No
      difference was noted in their choice between orthopedists and internists.
      Opinions varied widely, however, among younger doctors, but there was agreement
      among older doctors, suggesting the effect of the study and experience. On the
      other hand, some doctors recommended arthroscopic synovectomy for knees in the
      earlier stages of RA, but others did not recommend the arthroscopic surgery
      itself. Although this new methodology might include possible biases, we believe
      it should be considered in the research of rheumatology.

PMID- 11296452
TI  - [Evaluation of cerebrovascular events in patients with rheumatoid arthritis].
AB  - OBJECTIVE: We evaluated cerebrovascular events (cerebral infarction or cerebral
      bleeding) in patients with rheumatoid arthritis (RA). METHODS: Prognosis and the
      causes of death among 1100 RA patients from 1995 to 1999, were analyzed. 34 RA
      patients were complicated by cerebrovascular events. About them, hemoglobin,
      platelet, C-reactive protein, rheumatoid factor, total cholesterol, triglyceride,
      duration of disease, functional class, and dose of steroids per day were
      measured. RESULT: Among 1100 patients with RA, 90 died at the age of 70.2. Of
      these patients, 24 (26.7%) died of cerebrovascular events, 19 (21.1%) of heart
      failure, 16 (17.8%) of infectious diseases, 10 (11.1%) of malignant tumors, and 9
      (10%) of renal failure. When RA patients who died of cerebrovascular events were
      compared with those who died of other causes, the dose of steroid was
      significantly lower and the age was higher in RA patients who died of
      cerebrovascular events. However, there were no significant differences in total
      cholesterol and triglyceride levels between the two groups. Although the major
      cause of death in RA patients was reported to be complication by cardiovascular
      diseases, infectious diseases, or renal failure, the frequency of deaths was
      higher in elderly RA patients complicated by cerebrovascular events. When the
      frequency of complication by cerebrovascular events was investigated in all RA
      patients including those who survived, 24 died and 10 survived. The frequency of
      complication by cerebral infarction was higher than that of complication by
      cerebral bleeding in RA patients who died of cerebral events. CONCLUSION: RA
      patients can live longer with improvements in care and treatment, the number of
      elderly RA patients who may died of complication by cerebrovascular events may
      gradually increase.

PMID- 11296453
TI  - [A case of systemic lupus erythematosus with hemophagocytic syndrome and
      cytophagic histiocytic panniculitis].
AB  - A 23-year-old man, admitted because of high fever, polyarthralgia, butterfly rash
      and chest pain, was diagnosed as systemic lupus erythematosus (SLE) from the
      findings of positive antinuclear antibody and anti-DNA antibody. He was treated
      with 60 mg prednisolone daily, but as reducing the dose, white blood cell counts
      and platelet counts were decreased and fever, polyarthralgia, decrease of
      complements, increase of ferritin, hepato-splenomegaly and liver dysfunction were
      observed. Bone marrow specimen revealed phagocytosis of blood cells by
      histiocytes and he was diagnosed as hemophagocytic syndrome(HPS) due to active
      SLE. Methylprednisolone pulse therapy was effective temporarily, HPS recurred
      while reducing steroid, and cyclosporin was added. After a temporary remission,
      marked extensive swelling in the face appeared suddenly. Facial skin biopsy
      showed necrosis of fat cells and hemophagocytosis by histiocytes. Accordingly, he
      was diagnosed as panniculitis due to HPS and was treated successfully with
      intravenous cyclophosphamide pulse therapy and high dose of gammaglobulin.
      Several cases of HPS due to SLE have been reported recently, but this is a rare
      case of cytophagic histiocytic panniculitis (CHP) due to SLE.

PMID- 11296454
TI  - [A case of Sjogren's syndrome with dermatomyositis who died of rapidly
      progressive interstitial pneumonia].
AB  - We report a case of 55 year-old woman with six year history of Sjogren's syndrome
      developed fatal rapidly progressive interstitial pneumonia. She had been well
      until February 1999. She developed swelling and erythematous lesions in the cheek
      and hands in spring 1999. She was admitted to our hospital for investigations of
      skin lesions in May 1999. Physical examination on admission revealed small
      hemorrhagic lesions in the nailfold. Serum CK level was slightly elevated.
      Electromyogram and MRI suggested mild myositis in the proximal upper extremities.
      She was suspected to have dermatomyositis along with Sjogren's syndrome.
      Prednisolone 10 mg/day had been given for her skin problems since March 1999.
      Suddenly, dyspnea on exertion was appeared on 34th day of admission. Chest X-ray
      film showed an acute worsening of interstitial pneumonia. Methylprednisolone
      pulse therapy (1000 mg for 3 days) and cyclophosphamide pulse therapy (500 mg for
      a day) were started, and she was subsequently treated with 60 mg/day of
      prednisolone and 250 mg/day of Cyclosporin A. However, interstitial pneumonia did
      not respond to the treatment, and pneumomediastinum and pneumothorax have
      developed. She died of respiratory failure on 55th day. We consider that most
      likely explanation for fatal interstitial pneumonia is concomitantly occurred
      dermatomyositis.

PMID- 11296455
TI  - [The role of MMP in intervertebral disc tissues--from disc degeneration to
      herniated disc].

PMID- 11296456
TI  - [A multicenter cross-sectional study on the Health Related Quality of Life of
      patients with rheumatoid arthritis using a revised Japanese version of the
      Arthritis Impact Measurement Scales Version 2 (AIMS 2), focusing on physical
      disability and its associative factors].
AB  - OBJECTIVE: A multicenter cross-sectional survey was conducted to study the
      current status of Health Related Quality of Life (HRQL) of Japanese patients with
      rheumatoid arthritis using a revised Japanese version of the AIMS 2, to
      investigate the association among the self-report physical disability scores and
      demographic, socioeconomic, and clinical variables in these patients. METHODS: A
      Japanese version of the AIMS 2 was administered to the randomly chosen 1614
      patients with classical and definite rheumatoid arthritis attending arthritis
      clinics at eleven hospitals across the country. Self-report functional disability
      scores (FDSs) were calculated, by which patients were classified into five groups
      with graded levels of disability. Univariate correlations were examined between
      FDSs and the scores of the other four components of AIMS-HRQL, disease duration,
      age, medical costs, and physical and laboratory measures. Analysis of variance
      was performed to test for among level differences of these variables in each
      group of patients. Mean values and standard deviations of FDSs were calculated
      and analysis of variance was used to test for among level differences of the
      following factors: demographic, socio-economic, clinical measures, and treatment
      status. RESULTS: Among four scales composing the AIMS 2-HRQL, work disability
      scores were most strongly correlated with FDSs, followed by the scores of pain,
      affection and social interaction. The more severely disabled group proved to have
      weaker grip strength, higher joint count, longer disease duration, higher ESR and
      blood level of CRP, and lower level of Hb. Patients with more disabilities proved
      to be older, pay more medical costs, have longer duration of morning stiffness,
      and higher level of RF. Patients with more advanced Steinbrocker's functional
      class, doctor's global assessment, Steinbrocker's anatomical stage, higher daily
      dose of prednisolone intake, lower level of annual income and formal education,
      and patients taking more kinds of NSAIDs proved to be more severely disabled.
      Separate, single (never married, widowed), and divorced patients proved to be
      more severely disabled compared with married ones. Overall, females were more
      disabled than males. CONCLUSION: Physical disability is associated with the other
      important aspects of QOL, clinical signs and symptoms, and socio-economic
      conditions in RA patients. Prevention and management of physical disability
      should be seriously planned in consideration of the changes in these conditions
      in RA patients.

PMID- 11296457
TI  - [Epidemiology of type II diabetes, diagnosis, prevalence, risk factors,
      complications].
AB  - The prevalence of type 2 diabetes varies from 1.1% in sub-Saharian Africa to 3.3%
      in developing countries and to 5.6% in the industrialised countries, which brings
      the number of diabetics in the world to 135 millions. The projections of the WHO
      suggest a 35% increase in the prevalence of diabetes. This increase is explained
      by a progressively more sedentary life style, the overabundant and attractive
      food sources, the increase in life expectancy leading to diabetogenic ageing and,
      more specifically for Europe, the baby-boom effect after the Second World War,
      and finally, the changes in diagnostic criteria (fasting glucose > or = 1.26 g/L
      (7 mM) on two occasions, serum glucose > or = 2 g/L 2 hours after a loading dose
      of 75 g of glucose, in terms of prevalence of diagnosis and the prediction of
      specific diabetic complications). Age, birth weight (over or underweight) and
      heredity are established non-modifiable risk factors, whereas it is possible to
      change high risk behaviour, overweight, the syndrome of insulin resistance and
      hyperglycaemia. The major role of hyperglycaemia in the specific
      microangiographic complications of diabetes which are aggravated by hypertension,
      has been established. Hyperglycaemia does not seem to be a major risk factor in
      macroangiographic complications, especially coronary artery disease, in contrast
      to smoking, hypertension and certain lipid or fibrinolytic abnormalities.
      Epidemiological analysis of diabetes shows its invalidating feature, especially
      in terms of fatal vascular risk, which may be attenuated by correction of all
      associated metabolic abnormalities. The progression of the incidence of diabetes
      should alert the physician to be more attentive in the diagnosis and management
      of diabetes, especially with regards to early dietary intervention.

PMID- 11296458
TI  - [The coronary atherosclerosis of the diabetic].
AB  - Diabetes mellitus is one of the main risk factors of coronary atherosclerosis.
      The relative risk of cardiovascular disease is 2 to 4 times higher in type II
      diabetes than in the general population. The number of cases, especially type II,
      is increasing, especially as the definition of diabetes has been changed recently
      by the specialist scientific societies (American Diabetic Association, World
      Health organisation and ALFEDIAM) to include all patients with fasting glucose
      levels > or = 7 mmol/L on two occasions. Therefore, in the next 25 years, the
      number of diabetic patients will probably double, not only because of this new
      definition but also because of the combined effects of an ageing population,
      dietary changes (with an increase in obesity) and a progressively more sedentary
      and urbanized life-style in the so-called "emerging" countries.

PMID- 11296459
TI  - [Silent ischemic cardiopathy: which diabetics to examine?].
AB  - Non-Invasive coronary investigations are positive in 12 to 52% (average 22%) of
      type II diabetics, and 11 to 30% (average 17%) of type i diabetics. These
      statistics vary according to bias of recruitment. Haemodynamic lesions are found
      at coronary angiography in 35 to 80% of patients who have at least one positive
      non-invasive investigation. Nine to 12% of diabetics have silent myocardial
      ischaemia (SMI) confirmed by coronary angiography, compared with 1.3 to 5.3% of
      non-diabetic controls paired for age and sex. The higher frequency of SMI in
      diabetics seems to be mostly due to the increased frequency of ischaemic heart
      disease in diabetics. The importance of cardiac autonomic neuropathy (CAN) in SMI
      is controversial. The risk factors associated with SMI are those usually
      associated with coronary artery disease: age, masculine gender,
      hypercholesterolaemia, hypertriglyceridaemia, hypertension, smoking, a family
      history of cardiovascular disease, insulin therapy (for type II diabetes),
      proteinuria, retinopathy, peripheral occlusive arterial disease.... The French
      recommendations for investigating SMI seem to be contradictory. A single risk
      score in a given patient could help codify the investigation of SMI in diabetics,
      but this type of score has not yet been validated.

PMID- 11296460
TI  - [Which coronary tests to use in asymptomatic diabetics?].
AB  - Coronary artery disease is a common, serious and insidious complication of
      diabetes. Myocardial ischaemia is often silent. All diabetics do not have the
      same coronary risk and, therefore, it is important to determine which
      investigations to perform and which patients. This strategy is justified because
      it allows identification of these cases which require a medical or an invasive
      (angioplasty, surgical revascularisation) approach, as these interventions may
      improve the prognosis. The first stage is clinical (investigation of
      cardiovascular risk factors). When more than two risk factors are found, further
      investigations are justified. Exercise stress testing provide reassuring
      diagnostic and prognostic data when maximal and negative. When sub-maximal,
      impossible or significantly ischaemic, a second investigation is useful. Holter
      ECG recording with analysis of ST variation lacks sensitivity and, above all,
      specificity. The diagnostic value of perfusion myocardial scintigraphy in the
      diabetic is not as good as that observed in the general population, but its
      prognostic value remains good. Ischaemia involving over 20% of the myocardium
      justifies therapeutic investigation. Stress echocardiography has been validated
      in the diagnosis and prognosis of coronary artery disease and its sensitivity and
      specificity are probably the same as those of scintigraphy. The authors conclude
      that the asymptomatic diabetic requires clinical and staged paraclinical
      investigation to assess prognosis and, depending on the results, the adoption of
      a beneficial therapeutic strategy.

PMID- 11296461
TI  - [Should the occurrence of a first coronary event change the management of
      diabetes?].
AB  - The coronary morbi-mortality is particularly high in type 2 diabetes, which
      represents the vast majority of all diabetes. Hyperglycemia is an independent
      vascular risk factor in the short and long-term. The relationship between the
      degree of hyperglycemia and vascular risk is linear with no threshold effect. The
      occurrence of a first coronary event is an occasion, though late, to review the
      management of all risk factors in diabetic patients. In these patients, intensive
      insulin therapy administered in the acute phase of infarction reduces
      cardiovascular mortality by 30% at 1 and 3 years. There are no specific studies
      of secondary prevention by optimal therapy of diabetes, but, in the UKPDS, the
      treatment of hyperglycemia with sulfonylurea or insulin only marginally reduced
      the number of cardiovascular events. On the other hand, treatment of obese
      patients with metformin significantly reduced the incidence of myocardial
      infarction and of mortality diabetes related. These results, though observed with
      the same level of glycemic control as in the other treatment groups, suggest a
      cardio-protective effect of metformin itself. These beneficial effects should be
      weighed up against the potential risk of lactic acidosis which still limits the
      widespread use of metformin in with coronary heart disease patients. Follow-up
      studies show that diabetic with coronary heart disease patients do not receive
      all effective therapeutic inventions in secondary prevention and that the
      treatment of hyperglycemia is often neglected. Close collaboration between
      cardiologists and diabetologists is necessary to improve the management of type 2
      diabetes.

PMID- 11296462
TI  - [Does diabetes change the anti-ischemic therapeutic options in the symptomatic
      coronary patient?].
AB  - The assessment of results of medical treatment, angioplasty and coronary bypass
      surgery in diabetic coronary patients is difficult because of the absence of
      distinction in the subgroups of type 1 and 2 diabetes and of stable and unstable
      angina. With respect to medical therapy, betablockers are practically without
      deleterious effects and are effective in diabetic populations. The same is true
      of other antianginal drugs. Conventional coronary angioplasty is associated with
      poorer results than the general population in the long-term, partly because of
      progression of the coronary artery disease and partly because of an increased
      incidence of restenosis. The use of stents improves these results, which are
      similar to those of the general population with single vessel disease or those
      without proteinuria. Coronary bypass surgery, despite a certain perioperative
      morbidity, is associated with an identical survival rate at 5 years as non
      diabetics, providing the internal mammary artery is grafted. The comparison
      between these methods is resumed in the ACIP study which opposes the 3
      strategies, in Morris et al's study comparing medical and surgical approaches
      and, finally, in the recent BARI trial where patients were randomly allocated to
      angioplasty or surgery. It would appear that the surgical strategy gives better
      results in multivessel disease. However, many reserves have been voiced because
      of the small numbers of patients, the high number of excluded patients and the
      fact that recent progress in angioplasty with widespread use of stenting
      associated with the prescription of new antiaggregant drugs was not taken into
      account.

PMID- 11296463
TI  - [The heart and diabetes: from physiopathology to practice. Conference
      proceedings. Deauville, France, 21-23 June 2000].

PMID- 11296464
TI  - [Blood pressure and heart rate regulation in diabetics].
AB  - Cardiac autonomic neuropathy (CAN) is frequent in subclinical stages. Its
      prognostic value has been demonstrated. Cardiac autonomic neuropathy induces
      different functional cardiac changes, especially a reduction in left ventricular
      contractility and changes in ventricular repolarisation. It is also associated
      with changes in the daily variations in blood pressure. The association of CAN
      and silent myocardial ischaemia significantly worsens the prognosis. The
      investigation of CAN in the greatest number of diabetic patients is therefore
      justified. The study of heart rate variations during deep respiration, active
      orthostatism or Valsalva manoeuvre, is still the reference. This method is
      simple, reproducible and may be carried out in the clinical setting in 10 to 15
      minutes. The results must be strictly interpreted with rigour with respect to
      age. Orthostatic hypotension is a late sign of sympathetic nervous system
      disease. Spectral analysis of blood pressure variations on orthostatism or the
      study of cutaneous blood flow during activating the sympathetic system tests of
      greater sensitivity, should be developed. The demonstration of subclinical CAN
      should lead to the careful use of drugs which may induce orthostatic hypotension
      and certain antiarrhythmics, to search for disorders of ventricular
      repolarisation and for silent myocardial ischaemia in diabetics with several risk
      factors.

PMID- 11296465
TI  - [Electrocardiographic changes and rhythm problems in the diabetic].
AB  - Diabetes is a cause of serious myocardial disease related to an increased
      incidence of coronary artery disease, probably aggravated by cardiac autonomic
      neuropathy (CAN). In its incipient form, CAN hardly changes the sinus rhythm with
      an increase in nocturnal heart rate but without an appreciable effect on the
      indices of variability. In more advanced forms, "CAN+", there are not only
      changes in the heart rate variability but also in ventricular repolarisation. It
      is classical to underline the value of the corrected QT interval but this index
      has little real value. The "QT dispersion", comparing the duration of ventricular
      repolarisation on the surface leads, is no better a marker from the theoretical
      point of view. The dynamics of ventricular repolarisation on the other hand seem
      to be much more indicative of ventricular myocardial disease. They are studied by
      evaluating the QT-heart rate relationship and its increase distinguishes clearly
      CAN diabetics from CAN+ diabetics. In addition, in the latter subjects, diurnal
      physiological increase in the heart rate dependency of the QT interval (QT/RR
      slope) disappears or even inverse. It is probably this phenomenon which is
      responsible for the traditionally increased risk of ventricular arrhythmias and
      particularly sudden death in diabetics with autonomic neuropathy.

PMID- 11296466
TI  - [Genetics of type II diabetes].
AB  - Type 2 diabetes is a multifactorial disease composed of subtypes strongly
      associated with environmental factors at one end of the spectrum and highly
      genetic forms at the other hand. The former forms have been largely elucidated in
      the last years by the identification of the 5 genes responsible for the autosomal
      dominant MODY subtype: glucokinase, and 4 transcription factors which play a key
      role in the development of the endocrine pancreas or in the expression of glucose
      metabolism genes. Apart from the monogenic forms of type 2 diabetes little is
      known about the nature of the genetic factors involved. Minor contributors
      include insulin, sulfamide receptor and some others. Genome scans of diabetic
      families have revealed susceptibility loci on chromosome 1q, 2p, 2q (where the
      gene calpain 10 was recently cloned), 3q, 12q and 20. The identification of
      diabetes susceptibility gene is the first step to define targets of new drugs
      against diabetes.

PMID- 11296467
TI  - Development and cross-cultural and clinical validation of a brief comprehensive
      scale for assessing hostility in medical settings.
AB  - This study presents the development and validation of a brief comprehensive
      hostility scale. Two items of each subscale from the Buss-Perry (1992) Aggression
      Questionnaire, most strongly correlated with their subscale score, were selected,
      yielding the eight-item New-Buss. Internal reliability was .66 to .81, and full
      and brief scales correlated r = .92 to .94. In Study 1 (95 Israeli students), New
      Buss scores were significantly higher in self-rated deviant or speeding drivers
      than nondeviant or nonspeeding drivers, respectively. In Study 2 (279 American
      students), New-Buss scores correlated significantly with Barefoot's Ho, Anger
      Out, Anger-In, and Agreeableness. In Study 3 (79 Israeli patients undergoing
      angiography), New-Buss scores were significantly correlated with coronary artery
      disease severity independent of SBP in men below age 60 alone but not in women.
      Our findings support the cross-cultural feasibility, reliability, and concurrent,
      construct, and criterion validity of the New-Buss.

PMID- 11296468
TI  - Personality and coping with a common stressor: cardiac catheterization.
AB  - The association between coping and personality was examined in a sample of 204
      cardiac catheterization patients who were asked to evaluate the use of specific
      coping strategies used to deal with their cardiac catheterization. Personality,
      as measured by the NEO Five-Factor Inventory (FFI), was moderately correlated
      with coping measures. In multivariate analyses, after considering confounding
      factors, Neuroticism was positively and Extraversion was negatively related to
      avoidance coping and Neuroticism was negatively associated with counting one's
      blessings as a coping strategy. Personality was not related to either problem
      solving or seeking social support coping strategies for individuals experiencing
      a cardiac catheterization. However, important covariates were associated with
      coping strategies. Not being married was negatively correlated with use of
      seeking social support and not having a confidant was negatively related with
      seeking social support and positively with avoidance. These results suggest that
      there are specific relationships between personality and coping, but these
      relationships are, for the most part, moderate in persons coping with a cardiac
      catheterization, and that coping processes are associated with individual
      differences in available social resources.

PMID- 11296469
TI  - Sense of coherence buffers relationships of chronic stress with fasting glucose
      levels.
AB  - Sense of coherence (SOC) was examined as a buffer of the relationship of chronic
      stress with fasting glucose and insulin levels. Spouse caregivers of persons with
      diagnoses of Alzheimer's disease (AD) (n = 73) were compared to controls [spouses
      of nondemented persons (n = 69)], group-matched on age/gender. After controlling
      for anger and coronary heart disease (CHD), interactions of SOC and gender
      explained variance in glucose (but not insulin) at study entry (T1) and 15-18
      months later (T2). However, this occurred only in caregivers. At both times SOC
      and glucose were negatively related in men caregivers but not in women caregivers
      or in controls. In caregivers (but not controls), SOC at T1 predicted glucose at
      T2, independent of gender, anger, and glucose at T1; and hassles at T1 appeared
      to mediate this relationship. Future research should examine SOC as a buffer of
      other chronic stressors and metabolic variables.

PMID- 11296470
TI  - Using disease-related and demographic variables to form cancer-distress risk
      groups.
AB  - The use of disease-related (i.e., stage, phase, perceived health) and demographic
      (i.e., age, education, income) variables to identify subgroups of cancer patients
      and survivors manifesting divergent risk for psychosocial adjustment problems was
      assessed. Clustering procedures distinguished three clusters across two
      subsamples. In each subsample, low-risk participants had a low stage, a later
      phase, high perceived health, an older age, and a high education and income;
      moderate-risk participants had a low stage, a later phase, high perceived health,
      a greater age, and a low education and income; and high-risk individuals had high
      stage, an earlier phase, low perceived health, an average age, and a low
      education and income. Mean difference analyses showed that low-risk participants
      had higher psychosocial adjustment than high- and moderate-risk participants.
      High-risk participants had lower psychosocial adjustment than moderate-risk
      participants. The risk for psychosocial adjustment problems may be influenced by
      disease-related and demographic variables, and implications for the targeting of
      interventions are discussed.

PMID- 11296471
TI  - Psychosocial versus nicotine-only self-report measures for predicting follow-up
      smoking status.
AB  - The most popular measure of tobacco dependence, the Fagerstrom Tolerance
      Questionnaire (FTQ), measures only tobacco-specific behaviors. In contrast, the
      most popular assessment of addiction among polydrug users is the Addiction
      Severity Index (ASI). Most of the subscales comprising the ASI are psychosocial
      measures, not drug-specific measures. A study was undertaken to compare the
      predictive utility of these two contrasting measures. The NAS (adapted from the
      FTQ) and the Addiction Severity Index (ASI) were used to predict future smoking
      status in a cohort of polydrug users followed annually for 3 years. The baseline
      NAS score explained more of the variance in Time 2 and Time 3 smoking status than
      did the ASI subscales. When previous smoking status was included as a covariate,
      however, the NAS no longer predicted future smoking status, whereas the ASI
      Subscales continued to explain significant variance in future smoking status.
      Results suggest that when past smoking behavior is known, a respondent's legal
      status and alcohol use may be more useful than a measure of tobacco dependence
      for predicting future smoking status.

PMID- 11296472
TI  - Presleep cognitions in patients with insomnia secondary to chronic pain.
AB  - This study had two primary objectives: (1) characterize the content of presleep
      cognitions of chronic pain patients and (2) evaluate the association between
      presleep cognitions and sleep disturbance. Thirty-one outpatients with benign
      chronic pain completed the Beck Depression Inventory, pain and sleep diaries and
      participated in an in vivo, presleep thought sampling procedure for 1 week in
      their homes. The three most frequently reported presleep cognitions were general
      pain-related thoughts (36%), thoughts about the experimental procedure (27%), and
      negative sleep-related thoughts (26%). Stepwise multiple regression analyses
      found the presleep thoughts pertaining to pain and environmental stimuli were
      significantly associated with sleep continuity, independent from the effects of
      depression and nightly pain severity. Pain severity was found to be positively
      associated with Wake After Sleep Onset Time. These results are consistent with
      cognitive-behavioral models of primary insomnia and suggest the content of
      presleep cognitive arousal may contribute to sleep disturbance secondary to pain.

PMID- 11296473
TI  - New data on the structure of the acyl pocket in cholinesterases.

PMID- 11296474
TI  - The role of estradiol in gonadotropin-dependent regulation of neutrophil
      function.

PMID- 11296475
TI  - Hormonal regulation of early embryogenesis in amphimicts and apomicts.

PMID- 11296476
TI  - Natural antibody catalytic activities in mice with autoimmune disorders.

PMID- 11296477
TI  - Gene enhancer of yellow 1 of Drosophila melanogaster codes for protein TAFII40.

PMID- 11296478
TI  - A new widely distributed nuclear protein involved in the regulation of
      transcription catalyzed by RNA polymerase II.

PMID- 11296479
TI  - Two Drosophila melanogaster homologues of the human TAFII30 have different
      functions.

PMID- 11296480
TI  - The role of adenoviral gene E4 in species-specific adenoviral reproduction.

PMID- 11296481
TI  - The effects of beta-casomorphine-7 and naloxone of the locomotor defense response
      of the cockroach Periplaneta americana to electrical stimulation.

PMID- 11296482
TI  - Introduction of mutant p53 into a wild-type p53-expressing glioma cell line
      confers sensitivity to Ad-p53-induced apoptosis.
AB  - Transient expression of the tumor suppressor gene p53 via adenoviral-mediated
      gene transfer induces apoptosis in glioma cells expressing mutant p53, while
      causing cell cycle arrest in cells with wild-type p53. To determine whether a
      change in p53 status of a wild-type p53-expressing cell line such as U-87 MG
      would alter its apoptotic resistant phenotype in response to Ad-p53 infection, we
      generated cell lines U-87-175.4 and U-87-175.13 via retroviral-mediated gene
      transfer of the p53 (175H) mutant into the U-87 MG parental line. Control cell
      lines U-87-Lux.6 and U-87-Lux.8 were also generated and express the reporter gene
      luciferase. Both U-87-175.4 and U-87-175.13, but not control cell lines,
      exhibited morphology characteristic of apoptosis after Ad-p53 infection.
      Furthermore, expression of other p53 mutants (248W, 273H) in U-87 MG also
      sensitized cells to Ad-p53-induced apoptosis. Apoptosis was confirmed by TUNEL
      and cell cycle analysis. Several p53 response genes were examined in cells
      infected with Ad-p53, and among these, BCL2, p21WAF1/CIP1, CPP32/caspase 3, and
      PARP showed differences in expression between U87-175 and U87-Lux cell lines.
      Taken together, our data demonstrate that the introduction of p53 mutants in U-87
      MG promotes an apoptotic response in association with adenoviral-mediated wild
      type p53 gene transfer. These results underscore the importance of glioma p53
      genotype for predicting tumor response to p53-based gene therapy.

PMID- 11296483
TI  - Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein
      in brain tumors.
AB  - Oxidative DNA damage generated by an attack of reactive oxygen species causes
      mutation or cell death that may lead to various diseases and may be related to
      initiation or progression of carcinogenesis. 8-Oxo-2'-deoxyguanosine (8-oxo-dG)
      is a major oxidative DNA damage product that can result in mutation, and hMTH1,
      human MutT homolog protein 1, has been identified as an enzyme that hydrolyzes 8
      oxo-dGTP to the monophosphate, thus preventing accumulation of 8-oxo-dG in DNA.
      With immunohistochemical approaches, we investigated accumulation of 8-oxo-dG and
      expression of hMTH1 in brain tumor tissues obtained from surgical and autopsy
      cases, including 42 neuroepithelial tumors, 5 meningiomas, 2 metastatic brain
      tumors, and 1 schwannoma. 8-Oxo-dG accumulation and hMTH1 expression were
      increased in various brain tumors. Nuclei of brain tumor cells were
      immunoreactive for 8-oxo-dG in all cases. In most cases, both nuclei and
      cytoplasm of the tumor cells were immunoreactive for hMTH1. Both 8-oxo-dG
      accumulation and hMTH1 expression were most evident in high-grade gliomas,
      indicating that oxidative stress was high in these gliomas. Thus, the defense
      mechanism against such oxidative stress may be enhanced as well. These results
      suggest that oxidative stress may play a role in tumor progression.

PMID- 11296484
TI  - Expression and localization of scatter factor/hepatocyte growth factor in human
      astrocytomas.
AB  - Scatter factor/hepatocyte growth factor (SF/HGF) is a pleiotropic cytokine that
      has been implicated in glioma invasion and angiogenesis. The SF/HGF receptor,
      MET, has been found to be expressed in neoplastic astrocytes as well as in
      endothelial cells of the tumor vasculature. Both SF/HGF and MET expression have
      also been described to correlate with the malignancy grade of human gliomas.
      However, most glioblastoma cell lines lack SF/HGF expression, raising the
      question of the cellular origin of SF/HGF in vivo. Using in situ hybridization,
      we analyzed glioblastomas, anaplastic astrocytomas, diffuse astrocytomas,
      pilocytic astrocytomas, and normal brain for the expression of SF/HGF mRNA. We
      detected strong SF/HGF expression by the majority of the tumor cells and by
      vascular endothelial cells in all glioblastoma specimens analyzed. Combined use
      of in situ hybridization with fluorescence immunohistochemistry confirmed the
      astrocytic origin of the SF/HGF-expressiong cells. In contrast, CD68
      immunoreactive microglia/macrophages, as well as vascular smooth muscle cells
      reactive to alpha-smooth muscle actin, lacked SF/HGF expression. In anaplastic,
      diffuse, and pilocytic astrocytomas, SF/HGF expression was confined to a subset
      of tumor cells, and signals were less intense than in glioblastomas. In addition,
      we detected SF/HGF mRNA in cortical neurons. SF/HGF expression was not up
      regulated around necroses or at tumor margins. MET immunoreactivity was observed
      in GFAP-expressing astrocytic tumor cells and endothelial cells as well as in a
      subset of microglia/macrophages. We conclude that in vivo, both autocrine and
      paracrine stimulation of tumor cells and endothelium through the SF/HGF-MET
      system are likely to contribute to tumor invasion and angiogenesis. Lack of
      SF/HGF expression by most cultured glioblastoma cells is not representative of
      the in vivo situation and most likely represents a culture artifact.

PMID- 11296485
TI  - Expression and localization of cyclin-dependent kinase 5 in apoptotic human
      glioma cells.
AB  - Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family,
      is expressed predominately in mature neurons and is implicated in neurite
      extension, neuronal migration, and neuronal differentiation. Cdk5 protein
      expression also has been associated with apoptosis in a number of nonneuronal
      model systems. In normal brain, substrates for Cdk5 include neurofilament and tau
      proteins. Because human tumors of glial origin can express neuronal proteins, we
      examined whether Cdk5 and its activator protein, P35, are present in early
      passage human glioblastoma multiforme (GBM) cells lines and primary tumor
      specimens. Here we report the expression of Cdk5 and an "active" proteolytic form
      of P35 in human GBM cells and demonstrate kinase activity of the holoenzyme. We
      also show that Cdk5 kinase activity and expression of its activator protein, P35,
      is increased in the human GBM cell line M059J after exposure to ionizing
      radiation and that P35 is localized within M059J cells undergoing apoptosis.
      These results suggest a possible role for Cdk5 in mediating apoptosis in human
      GBM cells.

PMID- 11296486
TI  - Characterization of initiated cells in N-methylnitrosourea-induced carcinogenesis
      of the CNS in the adult rat.
AB  - Glial tumors may originate from the malignant transformation of multipotent glial
      progenitor cells, but tools to study malignant transformation leading to gliomas
      are limited by the lack of biological systems that represent early stages of this
      disease in adult animals. In order to characterize the initiated cells that give
      rise to gliomas, we have employed the N-methylnitrosourea (MNU) model for
      induction of brain tumors in adult rats (Rushing et al., 1998). Specifically, we
      have isolated and cultured transformed (premalignant) cells from normal-appearing
      brains of rats exposed to MNU for 10 weeks and from histologically abnormal
      brains of rats exposed to MNU for 15 weeks. We compared them with cells cultured
      from control animals under identical conditions. Cultured cells were classified
      according to their morphology, immunophenotype, karyotype, proliferation
      capacity, and tumorigenicity in athymic mice. Cultures from untreated normal rat
      brains grew as monolayers and had normal karyotypes (42 X,Y), epithelioid
      morphology, and slow proliferative capacity (doubling time > 120 h). In contrast,
      cultured cells from brains of MNU-exposed animals had karyotypes that ranged from
      normal to highly aneuploid. Aneuploid lines grew rapidly in multilayers (doubling
      time < 24 h), had differentiated astrocytic or oligodendroglial morphology and
      immunohistochemical staining profile, and yielded tumors in athymic mice.
      Initiated cells with minor chromosomal aberrations assumed mixed bipolar or
      tripolar morphologies in high density cultures, proliferated rapidly, but showed
      contact inhibition and failed to induce tumors when injected s.c. in athymic
      mice. In general, lines showing no evidence of chromosomal aberrations had the
      most epithelioid morphology, proliferated slowly (doubling time > 72 h), and
      retained strict contact growth inhibition. The presumed undifferentiated glial
      progenitor cells in culture from either control or MNU-treated rats variably
      expressed markers such as vimentin, nestin, and NG2 proteoglycan, and they weakly
      expressed the mature astrocytic or oligodendroglial markers glial fibrillary
      acidic protein or galactocerbroside, respectively. These cultures differentiated
      to bipolar-tripolar morphology with concomitant maturation to a GFAP+ or GalC+
      phenotype upon exposure to secondary messengers such as dibutyryl-cyclic-AMP
      and/or growth factors such as basic fibrillary growth factor. Continuous
      stimulation with these messengers resulted in terminal differentiation and
      consequent death upon withdrawal of the stimulus. These results provide
      information that could lead to detailed characterization of initiated,
      premalignant cells in the adult brain and to a better understanding of glial
      carcinogenesis.

PMID- 11296487
TI  - Retraining of extinguished Pavlovian stimuli.
AB  - Five Pavlovian magazine approach experiments with rat subjects examined the
      mechanisms by which reconditioning restores extinguished responding. Experiments
      1, 2, and 3 found that retraining did not destroy the spontaneous recovery with
      the passage of time that is characteristic of extinguished stimuli. Experiments 4
      and 5 found evidence that retaining after extinction enhanced the strength of the
      originally trained associations. Together these results suggest that, just as
      extinction does not destroy original acquisition but superimposes some
      decremental process, so retraining does not destroy that decremental process but
      instead superimposes further associative learning.

PMID- 11296488
TI  - Self-administration cues as signals: drug self-administration and tolerance.
AB  - There is evidence that drug-associated exteroceptive cues elicit compensatory
      conditional responses (CCRs) that contribute to tolerance. The authors evaluated
      whether interoceptive, self-administration cues (SACs) similarly contribute to
      tolerance. In Experiments 1 and 2, the ataxic effect of ethanol was measured in
      rats that self-administered (SA) ethanol--by either oral consumption or
      intragastric infusion--and in rats that were yoked (Y) to these self
      administrators. In both experiments, the ataxic effect of ethanol was more
      pronounced in Y than in SA rats. In addition, SA rats failed to display usual
      levels of tolerance when ethanol was administered in the absence of SACs and
      displayed a CCR of hypertaxia in response to SACs not followed by ethanol. The
      results of Experiment 3 indicate that the ataxic effect of intravenous heroin
      also was greater in Y than in SA rats. The findings suggest that SACs contribute
      to drug tolerance.

PMID- 11296489
TI  - Relative validity of contextual and discrete cues.
AB  - Contextual conditioning during relative validity training was explored in 3
      experiments that used an appetitive Pavlovian conditioning preparation with rats.
      Magazine entries were the conditioned response. In Experiment 1, true
      discrimination (TD: AX+, BX-) training generated weaker conditioning of X than
      did pseudodiscrimination (PD: AX+/-, BX+/-) training. The context showed a
      similar relative validity effect. Also, both PD training and simple partial
      reinforcement (X+/-) reduced contextual conditioning more than did unsignaled
      food, a demonstration of relative validity using partial reinforcement.
      Experiments 2 and 3 used within-subject and between-subjects designs,
      respectively, and showed that relative validity was determined by the summation
      of differences in conditioning to both the common element (X) and the context.
      Our results are consistent with an attentional model or with a computational
      comparator model but not with the Rescorla-Wagner (R. A. Rescorla & A. R. Wagner,
      1972) model.

PMID- 11296490
TI  - Combined effect of context change and retention interval on interference in
      causality judgments.
AB  - Four experiments studied the effects of context change and retention interval on
      retroactive interference in human causal learning. Experiment 1 found evidence of
      retroactive interference. Experiment 2 found that either a 48-hr retention
      interval or a change in the context after the interference treatment decreased
      retroactive interference. An interaction between context change and retention
      interval effects was also found, eclipsing the context change effect after the 48
      hr retention interval. Experiments 3 and 4 found additivity between context
      change and retention interval effects when participants were remained of the
      difference between physical contexts before the test, independently of whether
      the context change involved a return to the original acquisition context. These
      results add to the evidence suggesting that spontaneous forgetting is caused by a
      change in either the physical or the temporal contexts where information is
      acquired.

PMID- 11296491
TI  - Timing and the control of variation.
AB  - Two rat experiments shed light on how variation in behavior is regulated.
      Experiment 1 used the peak procedure. On most trials, the 1st bar press more than
      40 s after signal onset ended the signal and produced food. Other trials lasted
      much longer and ended without food. On those trials, the variability of bar-press
      duration increased greatly after the 1st response more than 40 s after signal
      onset. In Experiment 2, which asked whether the increase was due to the omission
      of expected reward or the decrease in reward expectation, reward expectation had
      a strong effect on response duration, whereas omission of expected reward had
      little effect. In both experiments, response rate and response duration changed
      independently, suggesting that they reflect different parts of the underlying
      mechanism. In Experiment 1, response durations implied that timing of the signal
      was more accurate than the rate-vs.-time function might suggest. Experiment 2
      suggested that lowering reward expectation increases variation in response form.

PMID- 11296492
TI  - Treatments that weaken Pavlovian conditioned fear and thwart its renewal in rats:
      implications for treating human phobias.
AB  - In experiments using a total of 144 albino rat subjects, the authors assessed the
      ability of fear-weakening treatments to prevent fear renewal (relapse).
      Conditioned suppression of operant behavior served as the measure of fear in an A
      B-A (acquisition-treatment-test) renewal paradigm. In Experiment 1, 100
      nonreinforced exposures to a feared cue during treatment (extinction) did not
      reduce fear renewal relative to 20 exposures. In Experiment 2, explicitly
      unpaired (EU) treatments thwarted both renewal and reacquisition. In Experiment
      3, conditioned inhibition (CI) and differential conditioning (DC) treatments
      weakened renewal and resisted both reacquisition and a form of reinstatement. In
      Experiment 4, EU, DC, and CI treatments all thwarted renewal. Evidence suggested
      that the ability of the treatments to do so reflected the combined effects of
      transfer of extinction across treatment and test contexts and habituation to the
      unconditioned stimulus.

PMID- 11296493
TI  - Surgery in the pregnant patient.

PMID- 11296494
TI  - Public perception of perception.

PMID- 11296495
TI  - The role of attention in temporal integration.
AB  - When two visual patterns are presented in rapid succession, their contours may be
      combined into a single unified percept. This temporal integration is known to be
      influenced by such low-level visual factors as stimulus intensity, contour
      proximity, and stimulus duration. In this study we asked whether temporal
      integration is modulated by an attentional-blink procedure. The results from a
      localisation task in experiment 1 and a detection task in experiment 2 pointed to
      two separate effects. First, greater attentional availability increased the
      accuracy of spatial localisation. Second, it increased the duration over which
      successive stimuli could be integrated. These results imply that theories of
      visible persistence and visual masking must account for attentional influences in
      addition to lower-level effects. They also have practical implications for use of
      the temporal-integration task in the assessment of group and individual
      differences.

PMID- 11296496
TI  - Eye-movement control in direction-coded visual search.
AB  - Subjects searched for a target among distractors which were arranged randomly or
      such that each distractor provided information about the relative position of a
      target. Trials were presented either in a blocked design (so that the subjects
      knew a priori the contextual information in the display) or in a mixed design.
      When the distractors provided information about target position, there were (i)
      shorter manual RTs, (ii) fewer fixations made in search of the target, (iii)
      longer mean fixation durations, (iv) shorter initial fixation durations, (v)
      shorter mean gaze shifts, (vi) a smaller area of fixation dispersion, and (vii) a
      greater percentage of optimally directed saccades. Except for gaze shifts, the
      results were uninfluenced by whether or not there was a blocked or a mixed
      presentation. The results of the study suggest that despite noise in the search
      mechanism, fixation durations were adjusted to process directly the currently
      fixated element(s).

PMID- 11296497
TI  - The effect of contrast on vertical motion processing asymmetries in 11-week-old
      infants.
AB  - Recent forced-choice preferential looking (FPL) experiments with random-dot
      patterns [Wattam-Bell, 1998 Investigative Ophthalmology & Visual Science 39(4)
      S885] found evidence for a perceptual asymmetry of vertical-motion processing in
      young infants: a preference for patterns that move downwards. This asymmetry was
      in the opposite direction to the asymmetry of vertical optokinetic nystagmus,
      which was biased towards upwards motion. However, the FPL bias was weak, and the
      object of present experiments was to explore the possibility that it could be
      enhanced by reducing stimulus contrast. In experiment 1, contrast thresholds for
      gratings moving upwards and downwards were compared, and no directional asymmetry
      at threshold was found. In experiment 2, the effect of contrast on infants'
      preference between simultaneously displayed upwards-drifting and downwards
      drifting gratings was examined. Infants showed no preference at 5% contrast, a
      marked preference for downwards motion at intermediate contrasts (10% and 20%),
      and a similar but smaller preference at 40% contrast. These results suggest that
      the vertical-motion asymmetry is a result of differences in the gains of
      directionally selective mechanisms for upwards and downwards motion.

PMID- 11296498
TI  - Development of infants' sensitivity to surface contour information for spatial
      layout.
AB  - The development of sensitivity to a recently discovered static-monocular depth
      cue to surface shape, surface contours, was investigated. Twenty infants in each
      of three age groups (5, 5 1/2, and 7 months) viewed a display that creates an
      illusion, for adult viewers, that what is in fact a frontoparallel cylinder is
      slanted away in depth, so that one end appears closer than the other.
      Preferential reaching was recorded in both monocular and binocular conditions.
      More reaching to the apparently closer end in the monocular than in the binocular
      condition is evidence of sensitivity. Infants aged 7 months responded to surface
      contour information, but infants aged 5 and 5 1/2 months did not. In a control
      study, twenty 5-month-old infants reached consistently for the closer ends of
      cylinders that were actually rotated in depth. As findings with other static
      monocular depth information suggest, infants' sensitivity to surface contour
      information appears to develop at approximately 6 months.

PMID- 11296499
TI  - Large errors in the perception of vertically are generated by luminance borders
      (integrated across space) not by subjective borders.
AB  - The rod-and-frame illusion shows large errors in the judgment of visual vertical
      in the dark if the frame is large and there are no other visible cues (Witkin and
      Asch, 1948 Journal of Experimental Psychology 38 762-782). Three experiments were
      performed to investigate other characteristics of the frame critical for
      generating these large errors. In the first experiment, the illusion produced by
      an 11 degrees tilted frame made by luminance borders (standard condition) was
      considerably larger than that produced by a subjective-contour frame. In the
      second experiment, with a 33 degrees frame tilt, the illusion was in the
      direction of frame tilt with a luminance-border frame but in the opposite
      direction in the subjective-contour condition. In the third experiment, to
      contrast the role of local and global orientation, the sides of the frame were
      made of short separate luminous segments. The segments could be oriented in the
      same direction as the frame sides, in the opposite direction, or could be
      vertical. The orientation of the global frame dominated the illusion while local
      orientation produced much smaller effects. Overall, to generate a large rod-and
      frame illusion in the dark, the tilted frame must have luminance, not subjective,
      contours. Luminance borders do not need to be continuous: a frame made of sparse
      segments is also effective. The mechanism responsible for the large orientation
      illusion is driven by integrators of orientation across large areas, not by
      figural operators extracting shape orientation in the absence of oriented
      contours.

PMID- 11296500
TI  - The role of the centre of projection in the estimation of slant from texture of
      planar surfaces.
AB  - Displays were presented consisting of a perspective projection of a regular
      square grid, made up of vertical and horizontal equally spaced white lines, that
      was slanted in depth. The surface was viewed monocularly, through a circular
      aperture. A range of slants was shown (0 degree, 10 degrees, 20 degrees, 30
      degrees, 40 degrees, 50 degrees, or 60 degrees) and the observers' task was to
      match the slant by means of a mouse-driven probe. The viewing distance (50, 75,
      or 100 cm) as well as the focal distance (25, 50, 75, 100, or 125 cm) were
      varied. We expected the estimation error to be smallest when the viewing distance
      and the focal distance coincided. This was not the case. Instead, subjects seemed
      to use the perspective deformation of the texture elements in the stimulus
      display to make a slant estimation, regardless of the specific combination of
      viewing distance and focal distance.

PMID- 11296501
TI  - 'Perceiving the present' as a framework for ecological explanations of the
      misperception of projected angle and angular size.
AB  - An implicit, underlying assumption of most Helmholtzian/Bayesian approaches to
      perception is the hypothesis that the scene an observer perceives is the probable
      source of the proximal stimulus. There is, however, a nontrivial latency (on the
      order of 100 ms) between the time of a proximal stimulus and the time a visual
      percept is elicited. It seems plausible that it would be advantageous for an
      observer to have, at any time t, a percept representative of what is out there at
      that very time t, not a percept of the recent past. If this is so, it implies a
      modification to the implicit hypothesis underlying most existing probabilistic
      approaches to perception: the new hypothesis is that, given the proximal
      stimulus, the scene an observer perceives is the probable scene present at the
      time of the percept. That is, the hypothesis is that what an observer perceives
      is not the probable source of the proximal stimulus, but the probable way the
      probable source will be when the percept actually occurs. A model of an
      observer's typical movements in the world is developed, and it is shown that
      projected angles are perceived in a way consistent with the way the probable
      source will project to the eye after a small time period of forward movement by
      the observer. The predicted and actual direction of projected-angle misperception
      is sometimes toward 90 degrees and sometimes away from 90 degrees, depending on
      whether the probable source angle is lying in a plane parallel or perpendicular
      to the probable direction of motion, respectively. The perception of angular size
      for lines in a figure with cues they are lying in a plane perpendicular to the
      direction of motion is also shown to fit the predictions of the model.

PMID- 11296502
TI  - The glare effect and the perception of luminosity.
AB  - The impression of self-luminosity in the glare effect was studied in two
      experiments. In experiment 1 the target (CS) was set to the highest luminance of
      the field and subjects were asked to adjust the luminance ramp of the inducers
      (R) against five backgrounds (B) to the point where they began to see CS as self
      luminous. It was found that there is a linear relationship between background and
      luminance ramp. Another group of subjects carried out the same task in experiment
      2, but this time CS and R were linked together so that CS would always have the
      same luminance as the highest luminance level of R, as adjustments were
      performed. It was found that: (i) adjustments were always lower than the highest
      luminance available; (ii) the linear relationship between background and
      luminance ramp was confirmed; (iii) observers reported a compelling impression of
      self-luminous grays. Data are discussed in relation to Bonato and Gilchrist's
      model for the perception of luminosity. The authors advance the hypothesis that
      luminance ramps are used at an early stage of encoding for the perception of
      luminosity.

PMID- 11296503
TI  - High-spatial-frequency tritanopia: S-filling-in or S-filtering-out?
AB  - It has long been an accepted fact that a small test field presented against a
      large background may change its colour appearance because the test-field
      background contrast is attenuated by the receptor colour channels unequally
      (Willmer, 1944 Nature 153 774-775; Hartridge, 1947 Philosophical Transactions of
      the Royal Society of London, Series B 232 519-671). Such an effect is usually
      called small-field tritanopia. However, as shown in the present report, a similar
      colour illusion can be achieved with a large test field as well, provided its
      spatial-frequency content is high enough to reveal the differential drop of
      contrast sensitivity for the receptor colour channels (high-spatial-frequency
      tritanopia). A few demonstrations are presented which show that a traditional
      explanation of high-spatial-frequency tritanopia (including small-field
      tritanopia), based on the hypothetical process of filling-in, is not correct. An
      alternative account, based on spatial filtering within the receptor colour
      channels, is put forward.

PMID- 11296504
TI  - Expertise and the perception of kinematic and situational probability
      information.
AB  - Two experiments were conducted on the nature of expert perception in the sport of
      squash. In the first experiment, ten expert and fifteen novice players attempted
      to predict the direction and force of squash strokes from either a film display
      (occluded at variable time periods before and after the opposing player had
      struck the ball) or a matched point-light display (containing only the basic
      kinematic features of the opponent's movement pattern). Experts out-performed the
      novices under both display conditions, and the same basic time windows that
      characterised expert and novice pick-up of information in the film task also
      persisted in the point-light task. This suggests that the experts' perceptual
      advantage is directly related to their superior pick-up of essential kinematic
      information. In the second experiment, the vision of six expert and six less
      skilled players was occluded by remotely triggered liquid-crystal spectacles at
      quasi-random intervals during simulated match play. Players were required to
      complete their current stroke even when the display was occluded and their
      prediction performance was assessed with respect to whether they moved to the
      correct half of the court to match the direction and depth of the opponent's
      stroke. Consistent with experiment 1, experts were found to be superior in their
      advance pick-up of both directional and depth information when the display was
      occluded during the opponent's hitting action. However, experts also remained
      better than chance, and clearly superior to less skilled players, in their
      prediction performance under conditions where occlusion occurred before any
      significant pre-contact preparatory movement by the opposing player was visible.
      This additional source of expert superiority is attributable to their superior
      attunement to the information contained in the situational probabilities and
      sequential dependences within their opponent's pattern of play.

PMID- 11296505
TI  - Last but not least. Flashing lines.
AB  - In a periodic pattern of horizontally and vertically aligned quadrangles, two
      sets of illusory lines are seen to pulsate at orthogonal orientations,
      corresponding to the directions of knight's moves on a chessboard. The illusion
      seems to be governed by subtle rules of long-range interactions between parallel
      and non-parallel orientation filters.

PMID- 11296506
TI  - A critical evaluation of the pitchfork analysis.
AB  - The pitchfork analysis has gained increasing acceptance among researchers and
      clinicians to evaluate the effects of orthodontic treatment that can be measured
      on lateral cephalometric radiographs. It is primarily used in Class II cases to
      distinguish between the skeletal and dental effects of such treatments. The aim
      of this study was to conduct an objective evaluation of the pitchfork analysis by
      comparing cephalometric data obtained by that method with those using the more
      conventional and established method of Bjork. The pitchfork analysis consistently
      provided an overestimation of the skeletal effects and an under-estimation of the
      dental changes. These results indicate that the pitchfork analysis is not
      sufficiently sensitive to distinguish between the skeletal and dental effects of
      orthodontic treatment.

PMID- 11296507
TI  - Relationships among facial type, buccolingual molar inclination, and cortical
      bone thickness of the mandible.
AB  - The purpose of this study was to evaluate the relationships between different
      facial types, and both the buccolingual molar inclination and cortical bone
      thickness of the mandible. The material consisted of 31 dry skulls of modern
      Japanese males from the Museum of the University of Tokyo. They all demonstrated
      normal occlusion with minimal dental discrepancy, and without crossbite or facial
      asymmetry. The buccolingual inclination of the second molar (M2) in the long
      faced subjects was significantly smaller than the same dimension in the average-
      and short-faced subjects. It was found that the teeth of long-faced subjects were
      more lingually inclined than those of the short-faced subjects. The cortical bone
      thickness of the first molar (M1) and M2 sections was thicker in short-faced
      subjects than in average- and long-faced subjects. The results of this study
      provide evidence that a significant, but complex relationship exists between
      structures of the mandibular body and facial types. The morphological features
      that relate to masticatory function and facial types are associated with the
      cortical bone thickness of the mandibular body, and the buccolingual inclination
      of the first and second molars.

PMID- 11296508
TI  - The radiographic localization of impacted maxillary canines: a comparison of
      methods.
AB  - This study compared two different radiographic techniques for localization of
      impacted maxillary canines: vertical parallax (from a panoramic and a maxillary
      anterior occlusal radiograph) and magnification (from a single panoramic
      radiograph). The radiographs and the information regarding the impacted canines
      were obtained retrospectively from records of patients treated in the Day Stay
      Unit of the Eastman Dental Hospital. The two different radiographic techniques
      were tested blind and compared for localization of the impacted canine by six
      examiners. The 'gold standard' used for the radiographic comparisons was the true
      position of the canine as recorded at operation. The results showed a wide
      variation between the six examiners in the prediction of the canine position with
      the two different techniques. Localization with vertical parallax was more
      successful overall than with magnification, although the difference failed to
      reach significance. Seventy-six per cent of the impacted canines could be
      successfully located with vertical parallax and 66 per cent with magnification.
      Further analysis showed that, while almost 90 per cent of the palatally impacted
      canines could be correctly detected with both techniques, less than half of the
      buccal canines could be detected with parallax and only one in 10 buccal canines
      could be detected with magnification. If a canine is suspected to be buccally
      placed from its appearance on a panoramic film and cannot be palpated, further
      views are justified.

PMID- 11296509
TI  - Ultrastructure of cementum and periodontal ligament after continuous intrusion in
      humans: a transmission electron microscopy study.
AB  - An ultrastructural study of the cementum and periodontal ligament (PDL) changes
      after continuous intrusion with two different and controlled forces in humans was
      carried out. Twelve first upper premolars, at stage 10 of Nolla, orthodontically
      indicated for extraction from six patients (mean age 15.3) were used. They were
      divided into three experimental groups, distributed intra-individually as
      follows: control (not moved), continuously intruded for 4 weeks with 50 or 100 cN
      force, utilizing a precise biomechanical model with nickel titanium super-elastic
      wires (NiTi-SE), which were developed and calibrated individually. The teeth were
      extracted, fixed, decalcified, and conventionally processed for examination in a
      Jeol 100 CX II transmission electron microscope. Evident signs of degeneration of
      cell structures, vascular components, and extracellular matrix (EM) of cementum
      and PDL were observed in all the intruded teeth, with more severe changes towards
      an apical direction and in proportion to the magnitude of force applied.
      Resorptive areas and an irregular root surface of the intruded teeth were
      noticed, according to the same pattern described above. Concomitant, areas of
      repair were also revealed in the cementum and PDL although the magnitude of
      forces remained the same throughout the experimental period. Thus, a reduction of
      continuous force magnitude should be considered to preserve the integrity of
      tissues.

PMID- 11296510
TI  - Long-term stability of dental arch form in normal occlusion from 13 to 31 years
      of age.
AB  - Based on observations of longitudinal changes in dental arch dimensions, it has
      been stated that an individuality of arch form and an integrity of this form
      exists. However, longitudinal studies evaluating arch form changes have rarely
      been reported in the literature. The purpose of this investigation was to use a
      computer-assisted method for the description and analysis of maxillary and
      mandibular arch form in a sample of normal occlusion subjects, and to evaluate
      the long-term stability in dental arch form from the age of 13-31 years. The
      study was carried out on 30 subjects of Scandinavian origin with normal
      occlusion, recorded at a mean age of 13.6 years and at follow-up at 31.1 years.
      Arch form analysis was based on a standardized photographic procedure,
      digitization of morphological landmarks, and a computerized form analysis in
      which arch form was described using eccentricity values of conics. No specific
      arch form could be found to represent the sample. Age changes occurred in arch
      form, although with large individual variations. For the mandible, a significant
      change to a more rounded arch form with age was found, which in males was
      accompanied by a significant increase in inter-molar distance and reduction in
      arch depth. There was also a significant correlation between change in mandibular
      arch form and increased irregularity of the lower incisors. These findings of
      lack of stability in arch form in normal occlusion subjects, when passing from
      adolescence into adulthood, further question the possibility of achieving
      stability post-orthodontically.

PMID- 11296511
TI  - Face, palate, and craniofacial morphology in patients with a solitary median
      maxillary central incisor.
AB  - The occurrence of a solitary median maxillary central incisor (SMMCI) is a very
      rare condition and might be a sign of a mild degree of holoprosencephaly. In this
      investigation, material from 10 patients, nine girls and one boy with a SMMCI (8
      17 years of age) registered in orthodontic clinics was examined. The purpose was
      to evaluate the clinical characteristics and craniofacial morphology in this
      group of patients. Oral photographs, study casts, profile radiographs, and
      orthopantomograms were analysed. The study showed that this group of SMMCI
      patients were characterized by an indistinct philtrum, an arch-shaped upper lip,
      absence of the fraenulum of the upper lip, a complete or incomplete mid-palatal
      ridge, a SMMCI, and nasal obstruction or septum deviation. The craniofacial
      morphology of the nine girls, compared with normal standards for girls showed a
      short anterior cranial base, a short, retrognathic and posteriorly inclined
      maxilla, and a retrognathic and posteriorly inclined mandible. Furthermore, the
      sella turcica had a deviant morphology in five of the 10 subjects. The results
      indicate that the presence of a SMMCI should not be considered as a simple dental
      anomaly, since it may be associated with other clinical characteristics and more
      complex craniofacial malformations. It is therefore suggested that the SMMCI
      condition in future studies is classified according to clinical symptoms and
      craniofacial morphology.

PMID- 11296512
TI  - Comparison of lip incompetence by remote video surveillance and clinical
      observation in children with and without cerebral palsy.
AB  - This study aimed to compare two methods of assessing lip position so that an
      appropriate method could be used to assess whether a relationship existed between
      lip position and drooling in children with cerebral palsy. This investigation
      compared the use of a new, remote video surveillance (RVS) technique with direct
      clinical assessment of lip position by determination of intra- and inter-examiner
      agreement. Lip position was assessed in both techniques using the Jackson lip
      classification. Two groups of school children took part: one group suffered from
      cerebral palsy (CP), but the second group consisted of unaffected individuals.
      Based on Kappa statistics, intra- and inter-examiner agreements were generally
      found to be moderate for the individual methods (kappa = 0.48-0.54), whilst
      agreement between the two methods was found to be good (kappa = 0.68). The
      results showed moderately good examiner-agreement in the assessment of lip
      position, using either method and the Jackson lip classification. Consequently,
      lip position can be assessed by either RVS or direct clinical assessment, the
      choice depending on the physical circumstances surrounding the assessor and
      operator preference. However, RVS may offer a more unobtrusive approach.

PMID- 11296513
TI  - Comparison of enamel colour changes associated with orthodontic bonding using two
      different adhesives.
AB  - The purpose of this study was to evaluate the enamel colour changes associated
      with bonding of brackets with a no-mix (one-phase) adhesive resin (Unite) and a
      glass-ionomer adhesive (GC Fuji Ortho). Thirty recently extracted premolars were
      used in the investigation. Black rectangular pieces of adhesive tape with a 3-mm
      diameter window were used to standardize the enamel surface intended for
      analysis. The teeth were divided into two groups of 15 teeth each, brackets
      (Starfire TMB) were bonded with the two adhesives, and the enamel surfaces were
      colourimetrically evaluated at three time intervals: (a) before bonding
      (baseline), (b) following debonding and cleaning, and (c) after artificial photo
      ageing for 24 hours. The CIE colour parameters (L*, a*, b*) were recorded and
      averaged for each material, interval group, and the corresponding colour
      differences (delta E) were calculated. The results were statistically analysed
      using two-way ANOVA repeated measures, and Scheffe multiple range test at alpha =
      0.05 level of significance. All differences noted exceeded the threshold for
      clinical detection (delta E = 3.7). The highest differences were recorded for the
      baseline-debonding interval for both adhesives used. No difference was found with
      respect to delta E between etching-mediated and no etching-mediated bonding
      implying that the debonding cleaning process involving adhesive grinding may be
      more invasive relative to acid etching with regard to enamel colour alterations.

PMID- 11296514
TI  - The effect of micro-etching on the retention of orthodontic molar bands: a
      clinical trial.
AB  - Failure of orthodontic bands occurs most frequently at the band-cement interface,
      when conventional glass ionomer cements are used. Modification of the band
      surface may improve clinical performance by increasing the mechanical interlock
      at this junction. The aim of this prospective study was to compare the retention
      of micro-etched and untreated first molar orthodontic bands in a randomized, half
      mouth trial. Seventy-nine patients had 304 bands cemented as part of routine
      fixed appliance therapy. The effect of micro-etching, patient age and gender,
      operator, molar crossbite, treatment mechanics, and arch on band failure was
      investigated. Failure rates and survival times were compared for each variable
      assessed. Micro-etched molar bands showed a significant reduction in clinical
      failure rate over untreated molar bands and an increase in mean survival time (P
      < 0.001). Of the other variables examined, only the presence of a molar crossbite
      had any significant effect on band failure (P = 0.004).

PMID- 11296515
TI  - Lipid formation by aqueous Fischer-Tropsch-type synthesis over a temperature
      range of 100 to 400 degrees C.
AB  - The formation of lipid compounds during an aqueous Fischer-Tropsch-type reaction
      was studied with solutions of oxalic acid as the carbon and hydrogen source. The
      reactions were conducted in stainless steel vessels by heating the oxalic acid
      solution at discrete temperatures from 100 to 400 degrees C, at intervals of 50
      degrees C for two days each. The maximum lipid yield, especially for oxygenated
      compounds, is in the window of 150-250 degrees C. At a temperature of 100 degrees
      C only a trace amount of lipids was detected. At temperatures above 150 degrees C
      the lipid components ranged from C12 to > C33 and included n-alkanols, n-alkanoic
      acids, n-alkyl formates, n-alkanals, n-alkanones, n-alkanes, and n-alkenes, all
      with essentially no carbon number preference. The n-alkanes increased in
      concentration over the oxygenated compounds at temperatures of 200 degrees C and
      above, with a slight reduction in their carbon number ranges due to cracking. It
      was also noted that the n-alkanoic acids increased while n-alkanols decreased
      with increasing temperature above 200 degrees C. At temperatures above 300
      degrees C synthesis competes with cracking and reforming reactions. At 400
      degrees C significant cracking was observed and polynuclear aromatic hydrocarbons
      and their alkylated homologs were detected. The results of this work suggest that
      the formation of lipid compounds by aqueous FTT reactions proceeds by insertion
      of a CO group at the terminal end of a carboxylic acid functionality to form n
      oxoalkanoic acids, followed by reduction to n-alkanoic acids, to n-alkanals, then
      to n-alkanols. The n-alkenes are intermediate homologs for n-alkan-2-ones and n
      alkanes. This proposed mechanism for aqueous FTT synthesis differs from the
      surface-catalyzed stepwise FT process (i.e., gaseous) of polymerization of
      methylene reported in the literature.

PMID- 11296517
TI  - Nutrient uptake by protocells: a liposome model system.
AB  - Over the past decade, several liposome-based models for protocells have been
      developed. For example, liposome systems composed of polymerase enzymes
      encapsulated with their substrates have demonstrated that complex
      compartmentalized reactions can be carried out under conditions in which
      polymeric products are protected from degradation by hydrolytic enzymes present
      in the external medium. However, such systems do not have nutrient uptake
      mechanisms, which would be essential for primitive cells lacking the highly
      evolved nutrient transport processes present in all contemporary cells. In this
      report, we explore passive diffusion of solutes across lipid bilayers as one
      possible uptake mechanism. We have established conditions under which ionic
      substrates as large as ATP can permeate bilayers at rates capable of supplying an
      encapsulated template-dependent RNA polymerase. Furthermore, while allowing the
      permeation of monomer substrates such as ATP, bilayer vesicles selectively
      retained polymerization products as small as dimers and as large as a transfer
      RNA. These observations demonstrate that passive diffusion could be used by the
      earliest forms of cellular life for transport of important nutrients such as
      amino acids, phosphate, and phosphorylated organic solutes.

PMID- 11296516
TI  - The lipid world.
AB  - The continuity of abiotically formed bilayer membranes with similar structures in
      contemporary cellular life, and the requirement for microenvironments in which
      large and small molecules could be compartmentalized, support the idea that
      amphiphilic boundary structures contributed to the emergence of life. As an
      extension of this notion, we propose here a 'Lipid World' scenario as an early
      evolutionary step in the emergence of cellular life on Earth. This concept
      combines the potential chemical activities of lipids and other amphiphiles, with
      their capacity to undergo spontaneous self-organization into supramolecular
      structures such as micelles and bilayers. In particular, the documented chemical
      rate enhancements within lipid assemblies suggest that energy-dependent synthetic
      reactions could lead to the growth and increased abundance of certain amphiphilic
      assemblies. We further propose that selective processes might act on such
      assemblies, as suggested by our computer simulations of mutual catalysis among
      amphiphiles. As demonstrated also by other researchers, such mutual catalysis
      within random molecular assemblies could have led to a primordial homeostatic
      system displaying rudimentary life-like properties. Taken together, these
      concepts provide a theoretical framework, and suggest experimental tests for a
      Lipid World model for the origin of life.

PMID- 11296518
TI  - Experimental shock chemistry of aqueous amino acid solutions and the cometary
      delivery of prebiotic compounds.
AB  - A series of shock experiments were conducted to assess the feasibility of the
      delivery of organic compounds to the Earth via cometary impacts. Aqueous
      solutions containing near-saturation levels of amino acids (lysine, norvaline,
      aminobutyric acid, proline, and phenylalanine) were sealed inside stainless steel
      capsules and shocked by ballistic impact with a steel projectile plate
      accelerated along a 12-m-long gun barrel to velocities of 0.5-1.9 km sec-1.
      Pressure-temperature-time histories of the shocked fluids were calculated using
      1D hydrodynamical simulations. Maximum conditions experienced by the solutions
      lasted 0.85-2.7 microseconds and ranged from 5.1-21 GPa and 412-870 K. Recovered
      sample capsules were milled open and liquid was extracted. Samples were analyzed
      using high performance liquid chromatography (HPLC) and mass spectrometry (MS).
      In all experiments, a large fraction of the amino acids survived. We observed
      differences in kinetic behavior and the degree of survivability among the amino
      acids. Aminobutyric acid appeared to be the least reactive, and phenylalanine
      appeared to be the most reactive of the amino acids. The impact process resulted
      in the formation of peptide bonds; new compounds included amino acid dimers and
      cyclic diketopiperazines. In our experiments, and in certain naturally occurring
      impacts, pressure has a greater influence than temperature in determining
      reaction pathways. Our results support the hypothesis that significant
      concentrations of organic material could survive a natural impact process.

PMID- 11296519
TI  - Interstellar ices as a source of CN-bearing molecules in protoplanetary disks.
AB  - A reliable model for the composition and evolution of interstellar ices in
      regions of active star formation is fundamental to our quest to determine the
      organic inventory of planetesimals in the early Solar System. This has become a
      realistic goal since the launch of the Infrared Space Observatory, which provides
      a facility for infrared spectroscopy unhindered by telluric absorption over the
      entire spectral range of vibrational modes in solids of exobiological interest.
      Interstellar molecules detected in the solid phase to date include H2O, NH3, CO,
      CO2, CH3OH, CH4, H2CO, OCS and HCOOH, together with a C identical to N-bonded
      absorber generically termed 'XCN'. In this article, we focus on cosmic synthesis
      of CN-bearing species, as this important class of prebiotic molecules may not
      have formed endogenously in significant quantities on early Earth if conditions
      were not highly reducing. Experiments in which interstellar ice analogs are
      subject to UV photolysis or energetic ion bombardment yield CN-rich residues with
      a spectral signature that matches a corresponding feature observed in young
      protostars enshrouded in dust and gas. CN-bearing species are also present in
      cometary ices, with a combined abundance comparable to the lower end of the range
      observed in protostars. Energetic processing of interstellar ices is thus a
      viable and potentially significant source of CN compounds in protoplanetary
      disks.

PMID- 11296520
TI  - Astronomical sources of circularly polarized light and the origin of
      homochirality.
AB  - Possible astronomical sources of ultraviolet circularly polarized light (UVCPL)
      which might be responsible for enantiomeric selection in interstellar organic
      molecules are considered, Synchrotron radiation from magnetic neutron stars has
      been suggested as a possible source of UVCPL. However, synchrotron radiation in
      these situations is not predicted to be strongly circularly polarized. Very few
      such sources show optical synchrotron radiation and in the few that do circular
      polarization has not been observed. Magnetic white dwarfs and white dwarf
      binaries (Polars) can be highly circularly polarized but any effect on molecular
      clouds and star formation regions must rely on rare chance encounters. Recent
      observations show that substantial levels of circular polarization are present in
      reflection nebulae in star formation regions. This mechanism produces polarized
      light exactly when and where it is needed in regions where star formation is
      occurring and organic molecules are known to be present.

PMID- 11296521
TI  - Planetary interchange of bioactive material: probability factors and
      implications.
AB  - It is now well-accepted that both lunar and martian materials are represented in
      the meteorite collections. Early suggestions that viable organisms might survive
      natural transport between planets have not yet been thoroughly examined. The
      concept of Planetary Interchange of Bioactive Material (PIBM) is potentially
      relevant to the conditions under which life originated. PIBM has been also
      invoked to infer that the potential danger to Earth from martian materials is non
      existent, an inference with, however, many pitfalls. Numerous impediments to
      efficient transfer of viable organisms exist. In this work, the lethality of
      space radiation during long transients and the biasing of launched objects toward
      materials unlikely to host abundant organisms are examined and shown to reduce
      the likelihood of successful transfer by orders of magnitude. It is also shown
      that martian meteorites studied to date assuredly have been subjected to
      sterilizing levels of ionizing radiation in space. PIBM considerations apply to
      both the solar system locale(s) of the origin of life and to the applicability of
      planetary protection protocols to preserve the biospheres of planetary bodies,
      including our own.

PMID- 11296522
TI  - ESA mission ROSETTA will probe for chirality of cometary amino acids.
AB  - New crucial theoretical investigations on the origin of biomolecular chirality
      are reviewed briefly. With the goal to investigate these theories our team is
      going to perform the 'chirality-experiment' in the near future with cometary
      matter. In 2012 the robotical lander RoLand will detach from the orbiter of the
      ROSETTA spacecraft and set down on the surface of comet 46P/Wirtanen in order to
      separate and identify cometary organic compounds via GC-MS in situ. Chiral
      organics will be separated into their enantiomers by application of 3 capillary
      columns coated with different kinds of stationary phases. Non-volatile compounds
      like amino acids will be derivatized in especially developed gas phase alkylation
      steps avoiding reactions in the liquid phase. The results of these preliminary
      gas phase reactions are presented in this article.

PMID- 11296523
TI  - Radioactivity as a significant energy source in prebiotic synthesis.
AB  - Radioactivity in the continental crust (due mainly to the isotopes 238U, 235U,
      232Th and 40K), as a energy source for chemical evolution in the early Archean
      (between 3.5 and approximately 4 Ga bp), is reviewed. The most important
      radioactive source in the continental crust is due to the production and
      accumulation of radioactive gases within the crust voids (porosity). The study of
      such mechanism has allowed us to reach a deeper understanding about the nature of
      the radioactive source and to describe its behavior, particularly with regard to
      prebiotic chemical evolution. An effective total energy of 3 x 10(18) Ja-1 has
      been obtained for a depth of 1 km, 4 Ga ago. If a depth of 30 km is taken, the
      obtained value is almost equal to the UV solar energy radiation (lambda < 150
      nm). Within the voids the radioactive source of the continental crust played a
      relevant role in prebiotic synthesis. In uranium deposits of the same age, the
      role of radioactivity must have been even more relevant in favoring chemical
      evolution.

PMID- 11296524
TI  - Cyanide self-addition, controlled adsorption, and other processes at layered
      double hydroxides.
AB  - Layered double hydroxides (LDH) are anion-exchanging materials of the type M(III)
      M(II)x(OH)(2x + 2)Y that occur abundantly in nature, and can concentrate,
      protect, and activate simple organic anionic species of possible relevance to the
      earliest organisms. We now wish to report progress in the following areas: 1)
      Internal vs. external uptake of anions. Ferrocyanide does not displace carbonate
      from synthetic hydrotalcite (Mg:Al LDH carbonate) but is nevertheless taken up on
      the outside of the particles. In other cases, anion uptake is controlled by
      specific hydrogen bonding requirements rather than by charge density alone, a
      feature that can be used to control whether uptake will be both internal and
      external, or external only. These two findings taken together have important
      implications for specific catalysis by LDH, since specific hydrogen bonding will
      affect the individual and relative conformations of substrate anions, and anions
      occupying space in the interlayer will be under tighter constraints than those
      adsorbed externally. 2) Specific reactions catalyzed by LDH. We have found that
      the LDH Mg2Al(OH)6Cl catalyzes the self-addition of cyanide, to give in a one-pot
      reaction at low concentrations an increased yield of diaminomaleonitrile and in
      addition, at higher (> or = 0.05 M) concentrations, a purple-pink material that
      adheres to the LDH. We are investigating whether this reaction also occurs with
      hydrotalcite itself, what is the minimum effective concentration of cyanide, and
      what can be learned about the products and how they compare with those reported
      at high HCN concentrations in the absence of catalyst.

PMID- 11296526
TI  - Prebiotic synthesis of nucleotides.
AB  - If an RNA-only world preceded more complex forms of life, then it is essential
      that the process whereby the first nucleotides were made be considered.
      Presumably there were no enzymes and no templates to facilitate the synthesis of
      the first nucleotides so another form of chemical evolution must have been
      involved. Answers to problems of this sort were sought vigorously in the 1960s
      and the early 1970s but many issues were left unresolved. Progress made in the
      last few years has added to this early work and brings us closer to a
      satisfactory solution. In this article key results, old and new, and some ideas
      as to how further progress is likely to be made are discussed. There are reasons
      for optimism. Substantial progress has been made on the synthesis of purines and
      ribose, phosphorylation and polyphosphorylation. The outstanding problems at this
      juncture relate to the synthesis of ribose to the exclusion of the other
      aldopentoses and to the problem of linking ribose to the purine bases.

PMID- 11296527
TI  - [Has the world forgotten Seveso?].

PMID- 11296525
TI  - The sugar model: catalysis by amines and amino acid products.
AB  - Ammonia and amines (including amino acids) were shown to catalyze the formation
      of sugars from formaldehyde and glycolaldehyde, and the subsequent conversion of
      sugars to carbonylcontaining products under the conditions studied (pH 5.5 and 50
      degrees C). Sterically unhindered primary amines were better catalysts than
      ammonia, secondary amines, and sterically hindered primary amines (i.e. alpha
      aminoisobutyric acid). Reactions catalyzed by primary amines initially consumed
      formaldehyde and glycolaldehyde about 15-20 times faster than an uncatalyzed
      control reaction. The amine-catalyzed reactions yielded aldotriose
      (glyceraldehyde), ketotriose (dihydroxyacetone), aldotetroses (erythrose and
      threose), ketotetrose (erythrulose), pyruvaldehyde, acetaldehyde, glyoxal,
      pyruvate, glyoxylate, and several unindentified carbonyl products. The
      concentrations of the carbonyl products, except pyruvate and ketotetrose,
      initially increased and then declined during the reaction, indicating their
      ultimate conversion to other products (like larger sugars or pyruvate). The
      uncatalyzed control reaction yielded no pyruvate or glyoxylate, and only trace
      amounts of pyruvaldehyde, acetaldehyde and glyoxal. In the presence of 15 mM
      catalytic primary amine, such as alanine, the rates of triose and pyruvaldehyde
      of synthesis were about 15-times and 1200-times faster, respectively, than the
      uncatalyzed reaction. Since previous studies established that alanine is
      synthesized from glycolaldehyde and formaldehyde via pyruvaldehyde as its direct
      precursor, the demonstration that the alanine catalyzes the conversion of
      glycolaldehyde and formaldehyde to pyruvaldehyde indicates that this synthetic
      pathway is capable of autocatalysis. The relevance of this synthetic process,
      named the Sugar Model, to the origin of life is discussed.

PMID- 11296528
TI  - [Development of a physical performance scale for patients with implanted
      pacemakers].
AB  - The development and the validation of the Pavia Physical Performance Scale (PPPS)
      is here presented. PPPS is a new instrument evaluating the physical performance
      of pacemaker implanted patients. Data comes from a cross-over clinical trial on
      the efficacy of two functions of the pacemaker device. Primary end-point is the
      improvement of the physical performance together with the quality of life. We
      used data of 168 patients actually enrolled and interviewed with the Pavia
      Physical Performance Scale. We first selected 30 Likert-type items; then we
      applied a statistical methodology of Homogeneity Analysis (HOMALS). We verified
      the homogeneity of the scale and the internal consistency (Cronbach's alpha =
      0.92). With the same methodology, we developed the final version of PPPS. The
      final version lists 20 items; based on the results of the psychometric analysis,
      we turned the Likert-type scoring into a binary scoring (1 = no limitation of
      physical activity, 0 = limitation or never tried). The external validity, trough
      an Analysis of Variance of PPPS mean scores within New York Heart Association
      classes (NYHA), has been performed. We found a negative linear trend of PPPS
      scores and NYHA classes. That means an association between high PPPS scores (good
      physical performance) and low NYHA classes (also good physical capacity). The
      Pavia Physical Performance Scale (PPPS) could be proposed as a valid and
      consistent scale aimed to evaluate physical performance in pacemaker implanted
      patients. We suggest to use it in the clinical practice in addition to more
      traditional techniques.

PMID- 11296529
TI  - [Financial law and tumor screening].

PMID- 11296530
TI  - [Indiscriminate cuts in health expenditure in the Puglia region].

PMID- 11296531
TI  - [Case-control study in an area of the province of Ferrara having a high mortality
      rate for lung tumors].
AB  - The province of Ferrara represents one of the areas with the highest mortality
      rate for lung cancer in Italy. The aim of the study is to evaluate the relative
      importance of the main known risk factors for lung cancer in that area. It is a
      case control study based on the population where the cases under study (249) are
      selected from subjects deceased over the period 1988-1993 in the territory of the
      ex USL 33 (Local Health Authority) of Comacchio, while the controls (500) lived
      in the same area. The statistical analysis showed the same information that can
      be found in other medical literature regarding the known risk factors: smoking
      (OR = 3.7-44.9 per n. cigarettes/die), spouse passive smoking (OR = 1.1), passive
      smoking due to social setting (pubs) (OR = 1.9), vegetable diet (OR = 0.4). A
      important role was played by the factors linked to socio-economic differences.
      There was a significant increase in risk for those who had lived in "casazze" in
      the area, which are typical homes of the poorer social classes. There was also a
      significant increase in risk for subjects with a lower level of education. To
      obtain these results the analysis method known as "classification trees" was also
      used in order to verify its possible use in the public health sector.

PMID- 11296532
TI  - [Which peer review is appropriate for studies carried out during a judicial
      inquiry?].

PMID- 11296533
TI  - [Communicating with health authorities and the public about asbestos risk in
      Biancavilla (CT)].
AB  - The high incidence of pleural mesothelioma observed in Biancavilla (Catania) is
      causally associated to the presence of amphybolic fibres in the volcanic rock
      used by the local construction industry. This paper examines risk communication
      in this setting, with respect to presentation of the epidemiologic findings and
      decision making in the field of environmental clean up. The central issues in
      communicating with health authorities have been evaluation of the causal link and
      connections between available knowledge and subsequent action. The public has
      been rapidly informed, through press and local broadcasting stations. It has been
      made clear that recommended interventions were of preventive nature, namely
      paving with asphalt roads that were previously paved with the local quarry's
      byproducts. It has been stated that expected benefits would be delayed in time.
      Compliance of the local community may be jeopardized by further delay in the
      implementation of this intervention.

PMID- 11296534
TI  - [Appeal to the Minister for the autonomy of the Agency for Public Health of the
      Lazio region].

PMID- 11296535
TI  - [Vinyl chloride and 1,2-dichloroethane: classification and assessment of
      carcinogenicity, guidelines, threshold values, and standards developed by
      national and international entities, organizations, and agencies].
AB  - International, national and regulatory classification, evaluation, guidelines and
      occupational exposure values regarding vinyl chloride and 1,2-dichloroethane,
      carried out by European Union (EU). Environmental Protection Agency (US EPA),
      International Agency for Research on Cancer (IARC), Italian National Advisory
      Toxicological Committee (CCTN), Occupational Safety and Health Administration
      (OSHA), World Health Organization (WHO), National Institute for Occupational
      Safety and Health (NIOSH), American Conference of Governmental Industrial
      Hygienists (ACGIH) and other institutions, have been considered with particular
      reference to the carcinogenic effects. Moreover information is reported in
      support of classification and evaluation and a short historical review since
      early 1970s, when first evidence that occupational exposure to VC could lead to
      angiosarcoma was published.

PMID- 11296536
TI  - [Physicians and incinerators].

PMID- 11296537
TI  - [Estimating non-response bias].

PMID- 11296538
TI  - [Waste management in Lombardy: the citizens speak].

PMID- 11296539
TI  - [Public health, epidemiology, and politics].

PMID- 11296540
TI  - [Looking for poor and docile patients].

PMID- 11296541
TI  - [Depleted uranium and tumors].

PMID- 11296542
TI  - Introduction to "nimesulide: beyond COX-2".

PMID- 11296543
TI  - Inhibition of gastric acid secretion by nimesulide: a possible factor in its
      gastric tolerability.
AB  - OBJECTIVE: To study the effect of nimesulide on acid secretion in mouse isolated
      stomach. METHODS: Isolated lumen-perfused mouse stomachs were monitored by pH
      electrodes (1). Gastric acid secretion was stimulated with histamine or 5
      methylfurmethide (5-MeF, a stable acetylcholine derivative), and the effect of
      nimesulide and indomethacin were studied alone and in combination with
      famotidine. RESULTS: The concentration-dependent stimulation of gastric acid
      output by histamine (Hill equation fitting parameters: log[A]50 5.44 +/- 0.15; p,
      1.01 +/- 0.11; alpha, 0.64 +/- 0.05) was inhibited by famotidine, and also by
      nimesulide (log r = 0.79 +/- 0.10 at 30 microM). However, nimesulide also reduced
      the maximum acid output. The shift produced by nimesulide and famotidine in
      combination indicated a greater than additive effect, suggesting that nimesulide
      was not acting at histamine H2-receptors (Shankley et al., 1988) (2).
      Indomethacin reduced acid secretion only at the highest concentration (100
      microM). Furthermore, the histamine-receptor-independent stimulation of gastric
      acid output by 5-MeF was greatly inhibited by nimesulide, which also suggests
      that nimesulide was acting on the parietal cell signaling pathway at a non
      histamine-receptor site. CONCLUSION: The relatively low risk of gastric mucosal
      damage with nimesulide is thought to involve its weak inhibition of gastric
      prostaglandin synthesis and its weak acidity, but another factor might be the
      ability to reduce gastric acid production. However, the effect of nimesulide on
      human gastric acid secretion remains to be investigated.

PMID- 11296544
TI  - The role of NSAIDs in psoriatic arthritis: evidence from a controlled study with
      nimesulide.
AB  - OBJECTIVE: To define the optimal dose of nimesulide (NIM) for treating psoriatic
      arthritis. METHODS: Eighty patients entered a 4-week, double-dummy, randomised,
      controlled study. Each patient was allocated to one of the following treatment
      groups: NIM 100 mg/day, NIM 200 mg/day, NIM 400 mg/day, or placebo. Primary end
      points for arthritis assessment were the scores for tender and swollen joints,
      and the physician's and patient's global assessment of efficacy. RESULTS: 76/80
      patients completed the study. NIM decreased the score for tender and swollen
      joints from baseline to the end swollen joints from baseline to the end of
      therapy (p < 0.05). Pain severity on a visual analogue scale (VAS) was reduced by
      NIM 200 mg (p = 0.03) or NIM 400 mg (p = 0.019) compared to placebo, as was
      morning stiffness (p = 0.038 and p = 0.008, respectively), but the trends with
      100 mg were not statistically significant. The investigators and patients
      assessed the global efficacy of the NIM 200 and 400 mg/day groups as better than
      placebo or NIM 100 mg. Side effects were observed in 12 patients (15%) during
      treatment. They were mostly mild, only one patient withdrew from the study as a
      result, and the trend for a higher incidence with NIM was not statistically
      significant. The Psoriasis Area Severity Index (PASI) and the ESR did not show
      any significant changes. Patients in the placebo group took more paracetamol per
      day compared with those in the NIM groups (p = 0.007). CONCLUSIONS: Nimesulide
      200 and 400 mg/day are effective and safe in psoriatic arthritis.

PMID- 11296545
TI  - Nimesulide, a balanced drug for the treatment of osteoarthritis.
AB  - World-wide experience with nimesulide confirms that it is an effective anti
      inflammatory drug in the treatment of osteoarthritis. A review of several studies
      in this condition confirms that nimesulide is at least as efficacious as other
      commonly used compounds. The safety profile of nimesulide, compared to reference
      drugs such as naproxen, etodolac and diclofenac, demonstrates superior
      gastrointestinal tolerability. Nimesulide is therefore a good choice for the long
      term treatment of OA.

PMID- 11296546
TI  - Differential regulation of interleukin-1 beta-induced cyclooxygenase-2 gene
      expression by nimesulide in human synovial fibroblasts.
AB  - Osteoarthritic (OA) human synovial fibroblasts (HSF) in culture were treated with
      the preferential COX-2 inhibitors nimesulide or NS-398, the non-specific COX
      1/COX-2 inhibitor naproxen, or dexamethasone, in the presence or absence of IL-1
      beta or LPS. Nimesulide or NS-398 inhibited IL-1 beta-induced PGE2 production at
      all concentrations tested, and in addition they suppressed IL-1 beta-induced COX
      2 mRNA expression and protein synthesis. These suppressive effects were most
      evident at therapeutic levels of the drugs. Mechanistic studies revealed that the
      drug-induced inhibition of COX-2 expression and synthesis was not promoter-based,
      but may be associated with the blockade of IL-1 beta-dependent calcium flux and
      increased cellular calcium levels.

PMID- 11296547
TI  - Non-steroidal anti-inflammatory drugs protect against chondrocyte apoptotic
      death.
AB  - Recent evidence suggests that the degradation of cartilage in osteoarthritis is
      characterized by chondrocyte apoptosis, but little is known about the molecular
      mechanisms involved or potential protective measures. In the present study, we
      used an immortalized chondrocyte cell line to explore the mechanisms of apoptotic
      chondrocyte cell death. We found that staurosporine-mediated chondrocyte death
      depended on the concentration and time of incubation, and coincided with
      increased Bax:Bcl-X mRNA expression, cytochrome C release, and activation of
      caspase-3. Pre-treatment of the cultures with nimesulide, a preferential
      cyclooxygenase (COX)-2 inhibitor, or with ibuprofen, a non-selective COX-1/COX-2
      inhibitor, protected the chondrocytes against the staurosporine-mediated nuclear
      damage and cell death in a concentration-dependent manner (10(-12) to 10(-6) M).
      Cell protection coincided with inhibition of the staurosporine-mediated induction
      of caspase-3 activation. Notably, the selective COX-2 inhibitor NS-398 (10(-6) M,
      24 hr pre-treatment) did not protect the cells against staurosporine-mediated
      apoptotic death. The data suggest that nimesulide and ibuprofen, in addition to
      their anti-inflammatory and analgesic benefits, may also have a protective effect
      in osteoarthritis through the inhibition of apoptosis in chondrocytes.

PMID- 11296548
TI  - [Pathogenic role of free-radical damage in radiation-induced atherosclerosis].
AB  - According clinico-epidemiological and experimental data there are positive
      correlation between irradiation and risk of atherosclerosis development. Taking
      into account that primary physico-chemical effects of ionising radiation
      influences on organism were connected with biologically active free-radical and
      their products formation, its pathogenic role under radiation-induced
      atherosclerotic injures of cardiovascular system is postulate. The development of
      atherosclerosis includes some consecutive stages beginning with free-radical
      activation in arterial tissues and blood. The free radical and their reactive
      species involves physico-chemical changes in plasmatic membranes and
      lipoproteins, damages of genome, cytotoxicity (apoptosis or reproductive death)
      and opposite effect of cytoprotection. The activation of intrinsic
      recovery/repair mechanisms after above types of injury has been associated with
      the induction of changes in amount of B,E- receptors and lipoproteins
      modification, the increase of the complexes lipoprotein-antibody. The subsequent
      events demonstrate the development of dyslipoproteinemias, the functional and
      morphological injures, appearance of "foam cells" and atherosclerotic damages of
      arterial wall.

PMID- 11296549
TI  - [Modern concept of peripheral erectile mechanisms].
AB  - The article describes the peripheral mechanisms of erection and control over
      them. This knowledge has been acquired as a result of the recent development of
      pharmacological research designed to study the regulation of erectile smooth
      muscle tone. Smooth muscle fibres of the corpora cavernosa and arteries supplying
      the penis relax in response to a reduction of intracellular calcium. This
      relaxation allows both an increase of the blood flow to the penis and opening of
      sinusoid spaces. Cyclic nucleotides, cGMP and cAMP, are intracellular messengers
      of the mediators acting on smooth muscle fibres and regulating these
      intracellular calcium movements. Nitric oxide (NO) increases the intracellular
      cGMP concentration that triggers relaxation. Other proerectile mediators, such as
      vasoactive intestinal polypeptide, prostaglandin E1, are of the secondary
      importance. In contrast, neurotransmitters of the sympathetic nervous system
      (norepinephrine), neuropeptide Y, and endothelin induce contraction of cavernous
      smooth muscle fibres, thereby opposing erection. Oxygenation of the cavernous
      tissue is also an important factor in the regulation of local mechanisms of
      erection. Regulation of calcium sensitivity as well as functioning of
      intracellulare contact--gap junction are of certain interest. A better
      understanding of the peripheral pharmacology of erection opens the way to new
      pathophysiological and therapeutic prospects in the broad context of erectile
      dysfunction.

PMID- 11296550
TI  - [The Kiev period of the scientific activities of V. V. Pidvysots'kyi].

PMID- 11296551
TI  - [Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic
      agents].
AB  - We have investigated the effects of neuroleptic agents, haloperidol, pimozide and
      fluspirilen, that are used in clinics to treat psychiatric disorders, but
      reportedly have proarrhythmic side effects, on HERG-encoded K+ channels
      responsible for the rapid component of cardiac delayed rectifier K+ current, IKr.
      All three agents blocked HERG-directed IKr in Xenopus oocytes in a voltage
      dependent manner. The extent of the blockade increased with depolarization
      correlating with channels activation consistent with open-channel blocking
      mechanism. The IC50 values for the haloperidol-, pimozide- and fluspirilen
      induced blockade of fully activated IKr were 1.36, 1.74 and 2.34 mcM
      respectively. Neuroleptics did not affect the HERG channels steady-state
      activation and inactivation properties. Thus, the blockade of HERG channels may
      underly proarrhythmic actions of neuroleptics resulting in a slowing down of the
      repolarization phase of cardiac action potential, and prolongation of the
      electrocardiographic QT interval.

PMID- 11296552
TI  - [Age-related changes in the morphology and functional state of the heart].
AB  - The aim of this study was to assess age-related morpho-functional peculiarities
      of the heart on the basis of investigating the chrono-inotropic dependence of
      left ventricular [LV] myocardium. The results of this investigation are of
      importance for geriatric practice. They are necessary for determining the markers
      and elaborating the quantitative criteria of detecting the early stages of heart
      failure and finding the ways to its correction in elderly people. Twenty subjects
      aged 20-35 and forty four subjects aged 60-74 without clinical symptoms of
      cardiovascular pathology were investigated by means of stress-echocardiography.
      The indices of systolic and diastolic functions of the heart were studied by
      means of the transesophageal atrial electric pacing (TAEP) at baseline and at
      each frequency of pacing with the assessment of degree and type of LV myocardium
      hypertrophy. In all of the subjects investigated the results of TAEP were
      negative, i.e. they showed no signs of coronary insufficiency. In elderly people
      the increment values of contraction and relaxation velocity indices at the same
      pacing frequency were significantly lower (P < 0.05) in comparison with ones
      obtained in younger subjects. In elderly people a decrease of the maximal
      relaxation velocity occurred at submaximal age-related heart rate (on the average
      135 beats/min) as compared to intermediate pacing frequencies whereas in younger
      subjects a further increment of this value continued. The LV hypertrophy
      developing with ageing plays on the one hand a compensatory role but on the other
      hand it deteriorates the diastolic function. The inefficiency of work of the old
      heart while pacing is an important factor limiting functional capabilities of the
      heart.

PMID- 11296553
TI  - [Spontaneous transient outward currents in smooth muscle cells of the rat tail
      artery].
AB  - Spontaneous transient outward currents (STOCs) were studied in the rat tail
      artery smooth muscle cells using standard patch-clamp recording techniques in the
      whole-cell configuration. STOCs evoked by membrane depolarization from -30 to 20
      mV varied in size from 50 to 1000 pA, their amplitude increased with membrane
      depolarization. These currents were inhibited by 1 mM TEA+. Both the frequency
      and the transferred charge (Q) were decreased in the absence of the extracellular
      Ca2+ or in the presence of the selective blocker of voltage-gated L-type Ca2+
      channels nifedipine. Application of caffeine at 1 mM increased both Q and the
      frequency of STOCs generation. These results indicate that STOCs are carried by
      large conductance Ca(2+)-dependent K+ channels and Ca2+ influx plays an important
      role in their activation.

PMID- 11296554
TI  - [Effect of nitric oxide donors on myocardial contractile activity].
AB  - On the isolated guinea--pig heart perfused under Langendorff preparation
      influence of the NO was studied. Donators of NO were nitroglycerinum and sodium
      nitroprusside. The myocardium contractive activity indeces and the coronary flow
      were studied before and after introduction of the guanilatcyclase blockade by
      methylene blue. The received results show that after introduction of
      nitroglycerinum and sodium nitroprusside myocardium contractive activity indeces
      decrease, and the coronary flow increases. After introduction of methylene blue
      myocardium contractive activity indeces almost do not change--that confirms the
      guanilatcyclase mechanism of NO effect.

PMID- 11296555
TI  - [Mechanisms of action of hypersodium medium on contractile activity of isolated
      rat heart].
AB  - Despite the high efficiency of elevated concentrations of sodium ions during
      myocardial ischemia and calcium paradox, the molecular mechanism of action of
      hypersodium media on heart contractions remains unknown. The purpose of the
      investigation was to study mechanisms by which raised concentrations of sodium
      ions alter cardiac contractility. Subsequent to initially developed reduced
      pressure in the left ventricle, elevated concentrations of sodium ions (200 mM
      instead of 140 mM NaCl, 3 mM KCl) produced an increased force of contractions of
      about 50%. The first stage of decrease in developed pressure did not relate to
      elevated tonicity of extracellular ionic millieu because lithium chloride (60 mM)
      did not produce the same effect. This action of elevated concentrations of sodium
      ions has been shown to be independent of blockers of ion-transporting systems
      (caffeine, verapamile, ethmozine, HMA or lidocaine). Raising the contractions by
      elevating the concentration of sodium ions (second stage) has been shown to be
      susceptible to sodium channel blockers (6-IA, benzamil, of phenamil) and to
      caffeine. Decreasing of potassium concentration (from 3 mM to 1-2 mM amplified,
      and increasing of K+ level (from 3 mM to 6 mM) attenuated the positive inotropic
      action of the elevated concentration of sodium ions. The positive inotropic
      effect due to elevated concentrations of sodium ions remains even after heart
      arrest by high concentrations of verapamile (2 mcM). Lithium chloride (60 mM)
      failed to elevate left ventricle developed pressure which was raised by elevated
      concentrations of sodium ions. These data suggest that the elevated concentration
      of sodium ions could effect Na+/Ca2+ exchange and provoke Ca2+ release from
      sarcoplasmic reticulum by changing the sodium gradient and resulting in Ca2+
      entry via Na+/Ca2+ exchange. These observations are consistent with the
      hypothesis of Leblanc N., Hume J.R. (1990) regarding sodium-induced calcium ion
      release from sarcoplasmic reticulum.

PMID- 11296556
TI  - [Effect of inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic
      acid oxidation on the immune response and the activity of the monoxygenase system
      and lipid peroxidation in the spleen and liver in mice].
AB  - In experiments on CBA mice we studied an immune response (IR) to sheep red blood
      cells, the activity of monooxygenase system and lipid peroxidation (LP) in a
      spleen and a liver after administration of indomethacin (IND) and
      nordihydroguaiaretic acid (NDGA) as the inhibitors of cyclooxygenase and
      lypoxygenase pathways of oxydation of arachidonic acid consequently. We have
      found that the both inhibitors changed differently the intensity of IR during its
      development. IND and NDGA activate the accumulation of antibody-forming cells in
      the mouse spleen in a dose-dependent fashion at both the inductive and fading
      phases of IR. At the productive phase these changes are less expressed and they
      are different depending on the dose of NDGA: the smaller dose increases the
      immune response and the bigger one decreases it a bit. Changes in the activity of
      the monooxygenase system in spleen and liver, affected with the both inhibitors,
      independing on the dose, were of different direction: after IND administration
      the activity increased, but after NDGA administration it decreased at all the
      terms of investigation, excluding the term of the 5-th day (productive phase of
      IR). In these conditions changes in the activity of IR were of opposite direction
      as compared to the changes in the monooxygenase system.

PMID- 11296557
TI  - [Catecholamine deposition and erythrocyte structural transformation in functional
      disorders of the sympathetic adrenaline system].
AB  - By means of ultra and cytochemical study the catecholamine inserts in
      erythrocytes look like dark lumps and beads the size and quantity of which being
      directly proportional to the sympathetic adrenaline system functional state.
      Under the conditions of catecholamine shortage the inserts reducing to fragments
      occurs and under catecholamine growth the increase in inserts size takes place.
      In both cases the erythrocyte structure disorder has been observed. Cytochemical
      method of catecholamine detection in erythrocytes also allows simultaneously to
      determine the erythrocyte morphological state.

PMID- 11296558
TI  - [Elevated level of TGF-alpha in the mucosa of small intestine of the rat
      following massive small bowel resection].
AB  - This study was performed to determine the changes in TGF-alpha production during
      compensatory regeneration of small intestine. For this purpose rats underwent
      either 70% small bowel resection or sham operation. Levels of TGF-alpha
      production were evaluated by radioreceptor assay and Western blotting. When
      compared with sham operation, small bowel resection resulted in threefold
      increase in the production of TGF-alpha at postoperative day 3. Possible
      mechanisms of TGF-alpha involvement in intestinal adaptation following massive
      small bowel resection are discussed.

PMID- 11296559
TI  - [Aspects of pulmonary circulation in healthy young adults in vertical and
      horizontal positions as affected by different kinds of weather].
AB  - The general pulmonary blood circulation in young healthy adults positively
      increases when influenced by the favourable I-st type and provided in horizontal
      body position. At the same time the venous blood flow is proportionally rising
      and the moderate vessels resistance improves that means the natural compensation.

PMID- 11296560
TI  - [Effect of different light and color stimulation of the cerebral hemispheres on
      cardiac rhythm self-regulation in healthy individuals].
AB  - To define functionally dominant hemisphere of the head brain in regulation of a
      heart rhythm 126 healthy persons were examined, right and left hemifields in eyes
      retinas by light of different length of a wave were stimulated, parameters of a
      heart rhythm autocorelogram before and after influence were investigated. The
      growth of coefficients 1k, m0, m0.3 is found out after influence by light with
      large length of a wave on the right hemisphere, that, taking into account the
      activation effect of this spectral range, can testify to domination of right
      hemisphere in regulation of a heart rhythm.

PMID- 11296561
TI  - [Effect of polyunsaturated fatty acid-containing food additives on erythrocyte
      enzyme activities and on hemoglobin affinity to oxygen in highly and low trained
      volleyball players during physical exertion].
AB  - It has been determined that in erythrocytes of high-qualified and low-qualified
      sportsmen-volleyboll after use of biopreparation "Polien", contained
      polyunsaturated fatty acids, glycolysis and pentose phosphate pathway reactions
      are intensified and glutathione reductase activity are decreased. At the same
      time the affinity of haemoglobin to oxygen in stabilized in organism of sportsmen
      before and after intensive muscle work. It has been shown, that specific and
      nonspecific changes of biochemical indexes are realized in organism of sportsmen
      with different qualification under intensive muscle work.

PMID- 11296562
TI  - [Antioxidative homeostasis of critically ill individuals].
AB  - Content of primary and secondary products of lipid peroxidation; fat soluble
      vitamins: A, E, carotene, tocopherol's metabolites and total antioxidative
      activity were investigated in experiments with serum blood of donors and sick
      people with the acute surgical trauma. It was showed that during the critical
      states of sick people there is watched the strain of adaptive systems of the
      whole organism with the resource mobilisation of fat soluble vitamins and
      appearance of signs of their exhaustion, modification of the direction of
      metabolism of the unsaturated fat acids from certain formation of eicosanoids to
      the avalanche looking lipid peroxidation with the accumulation of poisonous
      products in blood. Also there intensify the formation of active tocopherol's
      metabolites, what is necessary for the re-establishment of the violative balance
      in the system of antioxidative protection.

PMID- 11296563
TI  - [Intermittent hypoxic training with exogenous nitric oxide improves rat liver
      mitochondrial oxidation and phosphorylation during acute hypoxia].
AB  - It have been shown that NO plays primary role in several mitochondrial functions.
      Our objective for this study was to investigate whether exogenous NO (L-arginine)
      modulates the adaptive reactions of rat liver tissue respiration and lipid
      peroxidation on intermittent hypoxic training (IHT). In control animals the test
      with acute hypoxia (7% O2, 30 min) provoked sharp augmentation of ADP-stimulating
      tissue respiration with the increase of respiratory coefficient and
      phosphorylation rate, the decrease of O2 uptake efficacy and switching the energy
      supply to succinate oxidation pathway with the inhibition of aminotranspherase
      Krebs cycle substrates supply mechanism. The twice augmentation of malon
      dialdehyde content (MDA) was observed. The same hypoxic test but after 14 days of
      IHT (11% O2, 15-min sessions with 15 min rest intervals, 5 times daily) produced
      a stimulation of oxidative phosphorylation with primary activation of
      aminotranspherase pathway, the marked increase of ADP/O ratio on the background
      of a decrease of MDA content by 32%. The combination of IHT with L-arginine
      treatment (600 Mg/Kg intraperitoneally, daily before IHT sessions) provoked a
      decrease of tissue oxygen consumption, the inhibition of both aminotranspherase
      and succinateoxidase Krebs cycle substrates supply mechanism on the background of
      pronounced MDA decrease (by 120%) in comparison with untrained animals. L
      arginine effects abolished by the NO-synthase blocker L-NNA. We conclude that the
      combination of IHT which promotes the increase of inner adaptive mechanisms with
      NO-donors treatment could significantly increase the tolerance to episodes of
      acute hypoxia.

PMID- 11296564
TI  - [Electrical properties of intact rabbit aortic endothelium].
AB  - The ionic nature of membrane potential and electrical reactions to vasodilators
      and vasoconstrictors of intact endothelium of rabbit aorta have been
      investigated. It has been shown that K+ and Na+, but not Cl- permeability form
      membrane resting potential. The endothelium was hyperpolarized by ACh. ATP
      produced the triphasic reaction of short small depolarization, hyperpolarization
      followed by depolarization. Both noradrenalin and serotonin evoked
      depolarization.

PMID- 11296565
TI  - [Use of vilosen in the treatment of radiation damage of the immune system].
AB  - The possibility of vilosen usage for the immune system damage liquidation was
      studied. Rats obtained discrete rentgen irradiation during 1 month in the total
      dose of 4 Gr. Mice obtained internal 131I irradiation in a dose of 9.25 kBk/g. It
      was established that thymus and spleen masses, quantity of their cells, blood
      leukocytes and antibody production decreased by as external and internal
      irradiation. Irradiated animals treated with vilosen restored their immune system
      functional state partly or completely. The preparation was assumed to be used for
      the correction of immune system radiation damage.

PMID- 11296566
TI  - [Mechanism of thiol-dependence of acute phase proteins and serology of
      monospecific antisera in vitro].
AB  - For the donors and for the patients with inflammatory processes is thiol
      dependent the gear of immune responses in vitro an antigen--antibody on
      dynamics(changes) of change (+/- delta) of the contents SH- and S-S-group
      reaction mixtures. Thus, is conducted the analysis of interplay of proteins of an
      acute phase (CRP, orosomucoid and transferin) serums of a blood of the donors and
      patients with serology by related diagnostic (complementary) monospecific serums
      (MSS) against CRP (Anti-CRP), against Oroso (Anti-Oroso) i against Transf (Anti
      Transf). Is established, that as against the donors, for the patients with
      inflammatory processes these reacting are accompanied by a phenomenon of a
      liberation of energy of Ag(+)-sensing non proteins SH-groups and they occur in
      supernatants of deprotheinized of reaction mixtures. At the same time, both for
      the donors, and for the patients, these reacting are accompanied modification by
      changes kept in repair (+/- delta) proteins SH- and S-S-rpy[symbol: see text], in
      integral reaction mixtures (in which one protein did not deposit). Such data
      testify, that the inflammatory process, apparently, can be accompanied by such
      rearrangement of a structurally functional condition of proteins of an acute
      phase, that under operating MSS in reaction mixtures descends labelised blended
      disulfide of communications between them and low molecular weight thiols. As a
      result of it there is a liberation of energy of Ag(+)-sensing non proteins SH
      groups. This parameter can be used for an estimation of functional activity of
      proteins of an acute phase.

PMID- 11296567
TI  - [Rational and efficient enterovirus diagnosis].
AB  - BACKGROUND AND OBJECTIVE: Demonstration of the causative pathogen by isolating
      the virus in cell culture is taken as the standard in the diagnosis of diseases
      caused by enterovirus. When diagnosing the virus in cerebrospinal fluid (CSF),
      isolation of the virus has been largely replaced by the rapid demonstration of
      the virus using the reverse transcriptase polymerase chain reaction (RT-PCR),
      because of its greater sensitivity. The serological diagnosis is mostly made with
      the complement binding reaction (CBR). A new enzyme immunoassay for demonstrating
      anti-enterovirus IGM antibodies (IgM-EIA) allows a more rapid diagnosis from a
      single serum sample. It was the aim of this study to compare the diagnostic value
      of these various tests. METHODS: Several methods for demonstrating virus from
      faeces, swabs and CSF (virus isolation in cell culture and RT-PCR) and of
      antibodies in serum (IgM-EIA and CBR) were compared. The clinical material was
      obtained largely from children under the age of 10 years, many of whom had serous
      meningitis, flu-like symptoms or enteritis. In one cohort (C1), only stool or
      throat swabs were available for each of 154 patients. In the other cohort (C2) of
      164 patients, CSF and at least one serum sample were available in addition to
      occasional stool samples. RESULTS: From C1 enteroviruses were isolated from 32
      patients. rotavirus twice from stool or throat swab and rotavirus once from stool
      or throat swab, and herpes simplex once from throat swab. RT-PCR was positive 55
      times for enterovirus, five times false-negative when the virus had been
      isolated. In C2 enterovirus nucleic acid was demonstrated in 43 patients from
      CSF. Parallel serological tests gave positive IgM values for 15 patients, while
      CBR titres were raised in nine. CONCLUSIONS: Complementary tests of CSF, stool,
      swabs and serum samples by all possible combinations of viral isolation, RT-PCR
      and IgM-EIA improve the diagnosis of enterovirus-associated diseases. RT-PCR is
      the method of choice. The serological diagnosis should be confirmed by the
      demonstration of virus in stool or swab.

PMID- 11296568
TI  - [A humidification system for CPAP therapy in obstructive sleep apnea--evaluation
      of the effectiveness in changing climatic environmental conditions].
AB  - OBJECTIVE: Upper airway dryness is a frequent side-effect of nasal continuous
      positive airway pressure (nCPAP) therapy in obstructive sleep apnoea syndrome
      (OSA). In this situation, heated humidification is often used. Therefore, the
      present study aimed to investigate the humidification performance--defined as the
      maximum achievable humidity in the tube system of the CPAP device--of a heated
      humidifier (HH) offered as CPAP accessories, as a function of ambient air
      conditions (humidity and temperature). PATIENTS AND METHODS: In 30 patients (22
      male, 8 female, mean age 56.4 +/- 11.7 years) with OSA undergoing CPAP treatment,
      temperature (T) and relative humidity (RH) in the CPAP tube system were measured,
      with and without the HH Somnowave, until a steady state was achieved. At the same
      time, ambient T and RH in the examination room were recorded. T and RH were used
      to calculate the absolute humidity (AH). RESULTS: The conditions of the
      examination room during the examination nights were as follows: T = 21.9 +/- 2.8
      degrees C (15.2-26.9), RH 46.5 +/- 11.9% (21.7-69.1) and AH 9.2 +/- 3.2 g/m3 (3.7
      16.7). The steady state AH without HH was 9.6 +/- 3.0 g/m3 (4.1-15.4), that with
      HH (humidification performance) 23.2 +/- 2.8 g/m3 (19.1-29.9) (p < 0.001).
      CONCLUSION: Under the ambient conditions of humidity and temperature, commonly
      found in European bedrooms, the HH demonstrate a high humidification performance.
      Thus, it would appear that the HH is suitable for the treatment of dry upper
      airways under nCPAP therapy.

PMID- 11296569
TI  - [Laparoscopic splenectomy in thrombotic thrombocytopenic purpura. Surgical and
      hematological results in 2 patients].
AB  - HISTORY: Case 1. Thrombotic-thrombocytopenic purpura (TTP, Moschkowitz' disease)
      in a 57-year-old woman had for one year been treated conservatively. But when
      daily plasmapheresis was temporarily discontinued she developed behavioural
      changes and impaired speech, providing an indication for splenectomy. Case 2. A
      53-year-old woman with TTP had been similarly treated for one month. Splenectomy
      was indicated when neurological symptoms rapidly developed. INVESTIGATIONS: At
      admission, creatinine 110 mg/d, white cell count (WBC) 12.4 G/l haemoglobin 10.1
      g/dl, haematocrit 0.29, platelets 91 G/l. Prothrombin time (PTT) and
      thromboplastin time were normal. Patient 2. At admission, platelet count was
      below 10 G/l and she had various neurological abnormalities. Haemoglobin was 9.0
      f/dl, haematocrit 0.27. Platelet count, PTT, thromboplastin time and renal
      functions were normal. TREATMENT AND COURSE: Case 1. After plasmapheresis and
      administration of cryoprecipitate-free fresh frozen plasma (FFP) excess,
      laparoscopic splenectomy was performed. On the third postoperative day WBC count
      was 11.5 G/l, haemoglobin level was unchanged, but platelet count was now normal,
      as were PTT and thromboplastin time and renal functions. 8 and 32 months after
      the operation WBC count, haemoglobin, haematocrit and platelets were all normal.
      There were no neurological abnormalities postoperatively. Case 2. Laparoscopic
      splenectomy was performed after intensive haematological preparation. The pre-
      and postoperative course was uneventful and she was discharged on the 8th
      postoperative day, at which time her haemoglobin was 8.4 g/dl, haematocrit 0.25,
      while platelets, PTT, thromboplastin time and renal functions were all normal and
      remained so at follow-up 11 months later. There have been no neurological
      symptoms after the splenectomy. CONCLUSION: Laparoscopic splenectomy is a
      haematologically and surgically safe treatment of TTP and should be considered
      for all cases of TTP that fail to respond to conservative management.

PMID- 11296570
TI  - [Diagnosis of pulmonary hypertension].

PMID- 11296571
TI  - [Prevention of cancer and Alzheimer disease with non-steroidal anti-inflammatory
      agents].

PMID- 11296572
TI  - [Endoscopic monitoring in short segment Barrett esophagus].

PMID- 11296573
TI  - [Prostaglandin therapy in arterial occlusive disease].

PMID- 11296574
TI  - [Risk of osteoporosis by over-acidification of the organism and possible
      treatment by alkalizing therapy?].

PMID- 11296575
TI  - [Effect of nutrients on immune modulation].

PMID- 11296576
TI  - [Respiratory tract stents: less skepticism--more chances].

PMID- 11296577
TI  - Baseline computed tomography changes and clinical outcome after thrombolysis with
      recombinant tissue plasminogen activator in acute ischemic stroke.
AB  - OBJECTIVE: Intravenous recombinant tissue plasminogen activator (rt-PA) is the
      only therapy of proven value for patients with acute ischemic stroke (AIS).
      Controversy exists with regard to the prognostic significance of early computed
      tomography (CT) changes in patients receiving rt-PA for AIS. The authors
      retrospectively reviewed all cases of AIS who received intravenous rt-PA for AIS
      in University of South Alabama hospitals between January 1996 and May 1999. A
      neuroradiologist, blinded to clinical outcomes, reviewed all baseline CT scans
      for the presence of the following signs: hyperdense middle cerebral artery
      (HMCA), loss of gray-white differentiation (LGWD), insular ribbon sign (IRS),
      parenchymal hypodensity (PH), and sulcal effacement (SE). Modified Rankin Scale
      (mRS) score was recorded 90 days after thrombolysis, and clinical outcome was
      dichotomized as favorable (0-1) or unfavorable (2-6). The authors performed both
      univariate and multivariate analyses to investigate the relationship between
      early CT signs, baseline clinical variables, and functional outcome as measured
      by the 90-day mRS scores. Any one early CT finding was detected in 23(64%)
      patients. The frequency of specific findings were as follows: SE in 13 patients
      (36%), LGWD in 12 patients (33%), PH in 9 patients (25%), HMCA in 4 patients
      (11%), and IRS in 3 patients (8%) patients. There was no statistically
      significant association between the occurrence of these imaging findings and
      subsequent functional outcome after thrombolysis. The data suggest that the
      presence of subtle acute CT changes in AIS patients is not predictive of clinical
      outcome following administration of rt-PA as per National Institute of
      Neurological Disorders and Stroke protocol.

PMID- 11296578
TI  - Who should be screened for asymptomatic carotid artery stenosis? Experience from
      the Western New York Stroke Screening Program.
AB  - OBJECTIVE: Identification of significant asymptomatic carotid artery stenosis
      (ACAS) is important because of the stroke-risk reduction observed with carotid
      endarterectomy. The authors developed and validated a simple scoring system based
      on routinely available information to identify persons at high risk for ACAS
      using data collected during a community health screening program at various sites
      in western New York. A total of 1331 unselected volunteers without previous
      stroke, transient ischemic attack, or carotid artery surgery were evaluated by
      personal interview and duplex ultrasound. The main outcome measure was carotid
      artery stenosis > 60% by duplex ultrasound. In the derivation set (n = 887), 4
      variables were significantly associated with ACAS > 60%: age > 65 years (odds
      ratio [OR] = 4.1, 95% confidence interval [CI] = 2.6-6.7), current smoking (OR =
      2.0, 95% CI = 1.2-3.5), coronary artery disease (OR = 2.4, 95% CI = 1.5-3.9), and
      hypercholesterolemia (OR = 1.9, 95% CI = 1.2-2.9). Three risk groups (low,
      intermediate, and high) were defined on the basis of total risk score assigned on
      the basis of the strength of association. The scheme effectively stratified the
      validation set (n = 444); the likelihood ratio and posttest probability for ACAS
      in the high-risk group were 3.0 and 35%, respectively, and in the intermediate
      and low-risk groups were 1.4 and 20% and 0.4 and 7%, respectively. Routinely
      available information can be used to identify persons in the community at high
      risk for ACAS. Doppler ultrasound screening in this subgroup may prove to be cost
      effective and have an effect on stroke-free survival.

PMID- 11296579
TI  - Technetium-99m ECD single photon emission computed tomography in brain trauma:
      comparison of early scintigraphic findings with long-term neuropsychological
      outcome.
AB  - OBJECTIVE: The aim of this study was to assess the prognostic value of early
      brain scintigraphy in head injury in relation to long-term neuropsychological
      behavior. Twenty-four patients underwent technetium-99m (Tc-99m) ethyl cysteinate
      dimer single photon emission computed tomography (SPECT) within 1 month of the
      trauma. Scintigraphic abnormalities were evaluated both visually and
      semiquantitatively using the brain-to-cerebellum ratio method. The clinical
      neuropsychological investigation was conducted to evaluate abnormalities related
      to motor deficit, frontal behavior, and memory and language disorders. All
      patients had abnormalities on SPECT scan. One year after trauma, 14 patients
      (58%) had neuropsychological sequelae. The brain-to-cerebellum ratios in the left
      basal ganglia and brain stem were significantly decreased in patients with memory
      disorders (P = .03 and P = .02, respectively). Moreover, SPECT visual analysis
      indicated that low uptake in the basal ganglia, thalamus, and brain stem was
      associated with subsequent motor deficit, frontal behavior, and language and
      memory disorders. The authors conclude that brain SPECT can be valuable in
      predicting the neuropsychological behavior of survivors of severe head injury.

PMID- 11296580
TI  - Comparison between magnetic resonance phase contrast imaging and transcranial
      Doppler ultrasound with regard to blood flow velocity in intracranial arteries:
      work in progress.
AB  - OBJECTIVE: The authors evaluate blood flow velocities in the medial cerebral
      artery (MCA) and the basilar artery using magnetic resonance (MR) phase contrast
      technique in comparison with transcranial Doppler ultrasound (TCD). Eleven
      healthy male volunteers were studied. TCD of the MCA (n = 22) and basilar artery
      (n = 11) was performed. MR phase velocity mapping was done in each vessel at the
      same location where the TCD signal had been acquired. A 2-dimensional FLASH
      sequence with retrospective cardiac gating and an average temporal resolution of
      45 ms was used. Resistance indices (RIs) and pulsatility indices (PIs) were
      calculated for both modalities. The TCD insonation angle was measured
      retrospectively with MR, and TCD velocities were corrected based on these
      measurements. The comparison of flow velocities obtained with TCD and MR led to a
      low correlation coefficient with regard to the basilar artery and the MCA:
      maximum systolic velocity, r = 0.02 and r = 0.50, respectively; enddiastolic
      velocity, r = 0.47 and r = 0.65, respectively; mean velocity, r = 0.52 and r =
      0.66, respectively. The average PIs in the basilar artery and the MCA were 0.80
      and 0.81 with MR and 0.65 and 0.85 with TCD, respectively. The average RIs in the
      basilar artery and the MCA were 0.52 and 0.54 with MR and 0.52 and 0.55 with TCD,
      respectively. The TCD insonation angle differed significantly from the ideal
      value in the basilar artery (mean value = 32.6 degrees) and the MCA (mean value =
      26.5 degrees). The authors find a low correlation between velocities measured
      with MRI and TCD but similar results with regard to the PIs and RIs. Several
      sources of error, such as a nonideal TCD insonation angle, were identified.

PMID- 11296581
TI  - Regional brain atrophy is associated with physical disability in multiple
      sclerosis: semiquantitative magnetic resonance imaging and relationship to
      clinical findings.
AB  - OBJECTIVE: Brain atrophy may occur early in the course of multiple sclerosis (MS)
      and may be associated with disability. Brain magnetic resonance imaging (MRI) of
      114 MS patients (group A) were analyzed for regional atrophy (vs age-/gender
      matched controls) and T1 and T2 lesions using 4-point rating systems. Thirty-five
      separate patients (group B) were analyzed for cortical atrophy (ordinal scale),
      third ventricular width, and total T2 hyperintense lesion volume (computer
      assisted). In group A, regression modeling indicated that inferior frontal
      atrophy (P = .0003) and T2 lesions in the pons (P = .02) predicted physical
      disability (Expanded Disability Status Scale [EDSS] score). Secondary progressive
      (SP) versus relapsing patients were predicted by inferior parietal (P = .002),
      superior parietal (P = .006), temporal (P = .008), inferior frontal (P = .01),
      superior frontal (P = .01), cerebellum (P = .01), occipital (P = .01), and
      midbrain (P = .02) atrophy. SP patients were also predicted by total atrophy (P =
      .01) and third ventricular enlargement (P = .03) but not T1 or T2 lesions. In
      group B, the regression model predicting EDSS score included only superior
      frontal atrophy (r = 0.515, P = .002). Mean kappa coefficients of ordinal ratings
      were 0.9 (intraobserver) and 0.8 (interobserver). Ordinal ratings correlated well
      with quantitative assessments. The authors conclude that brain atrophy is closely
      associated with physical disability and clinical course in MS patients and can be
      appreciated using a semiquantitative MRI regional rating system.

PMID- 11296582
TI  - A pilot study of microembolic signals in patients with middle cerebral artery
      stenosis.
AB  - OBJECTIVE: There has been limited data on the frequency of microembolic signals
      in patients with middle cerebral artery (MCA) stenosis, especially during the
      acute phase of stroke. Using transcranial Doppler, the authors prospectively
      monitored the MCA segments distal to stenosis in 4 groups of patients for 30
      minutes: (1) symptomatic patients with acute ischemic stroke and MCA stenosis,
      (2) asymptomatic group patients with asymptomatic MCA stenosis, (3) control
      patients with acute ischemic stroke of undetermined etiology, and (4) normal
      people. A total of 60 patients completed the study. There were no microembolic
      signals in the asymptomatic, control, and normal groups. Among 20 patients in the
      symptomatic group, microembolic signals were detected in 3 patients (15%). The
      number of emboli ranged from 1 to 6 per 30 minutes. This is the first report of
      the presence of microembolic signals in acute stroke patients with MCA stenosis.

PMID- 11296583
TI  - Use of exponential diffusion imaging to determine the age of ischemic infarcts.
AB  - OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) detects acute
      ischemic infarcts with high lesion conspicuity. Determination of infarct age is
      difficult on DWI alone because infarct signal intensity (SIinfarct) on DWI is
      influenced by T2 properties ("T2 shine-through"). Maps of the apparent diffusion
      coefficient (ADC) reflect pure diffusion characteristics without T2 effects but
      have low lesion conspicuity. Thus, in clinical practice, combined use of DWI and
      ADC maps is required. Exponential DWI (eDWI) is an innovative means of MRI
      diffusion data analysis that merges the advantages of DWI and ADC maps. The
      authors hypothesized that SIinfarct on eDWI would correlate with infarct age. The
      authors studied 114 consecutive patients who had 120 ischemic strokes with
      clearly determined onset times and who underwent echo-planar DWI. The eDWI were
      generated by dividing the signal intensity on DWI by that on the corresponding T2
      image on a pixel-by-pixel basis. SIinfarct on eDWI was measured in the lesion
      core and expressed as a percentage of contralateral control tissue. On eDWI,
      relative SIinfarct changed significantly with infarct age (P < .0001). When
      patients were sorted in infarct-age groups, no significant differences were found
      within the first 120 hours. However, for patients studied within 5 days, the mean
      relative SIinfarct was significantly higher compared with patients studied > or =
      8 days after stroke (P < .05). For all infarcts up to 5 days old, the eDWI signal
      intensity was higher than control tissue (hyperintense appearance). All infarcts
      > 10 days old had an eDWI signal intensity lower than control tissue (hypointense
      appearance). The authors concluded that the use of eDWI, as a single set of
      images, reliably differentiates acute infarcts (< or = 5 days old) from infarcts
      > 10 days old. This feature would be expected to be helpful when the distinction
      between acute and nonacute infarction cannot be determined on clinical grounds.

PMID- 11296584
TI  - Cerebral perfusion in patients with syndrome X: a single photon emission computed
      tomography study.
AB  - OBJECTIVE: To test the hypothesis that syndrome X is a systemic vascular
      disorder, the authors studied 40 patients with this diagnosis using technetium
      99m hexamethylpropylene amine oxime and single photon emission computed
      tomography (SPECT) brain images. Twenty-three of 25 cases with definite
      myocardial perfusion defects diagnosed by thallium-201 myocardial perfusion SPECT
      also had multiple hypoperfusion areas in the brain versus 2 of 15 patients
      without thallium myocardial defects. The parietal lobes were the most common
      hypoperfusion areas, and cerebellum was the least common. Syndrome X is a
      systemic vascular disorder with a high incidence of hypoperfusion lesions of the
      brain and is usually coincident with myocardial defects.

PMID- 11296585
TI  - Morphology of the frontal operculum: a volumetric magnetic resonance imaging
      study of the pars triangularis.
AB  - OBJECTIVE: Broca's area, which includes the pars triangularis (PTR), is a
      neuroanatomical region important in speech and language production. Linear
      measures of the PTR have been found to be asymmetric, with the direction of the
      asymmetry correlating with language dominance determined by Wada testing. It is
      unclear, however, whether these linear measurements correlate with volumetric
      measures, and it is also unknown whether white matter and/or gray matter
      contribute differentially to these asymmetries. To investigate these issues,
      volumetric magnetic resonance imaging methodologies were used to measure the PTR
      in a group of healthy right-handed men (n = 12). There was a significant leftward
      asymmetry of the PTR using linear and volumetric measures. Linear measures of the
      left and right hemispheres were highly correlated with volumetric measures.
      Underlying gray and white matter both contributed to PTR asymmetry. Anatomical
      boundaries and four configurations (V, U, Y, and J) are discussed with reference
      to potential interhemispheric differences.

PMID- 11296586
TI  - Visualization of the IXth to XIIth cranial nerves using 3-dimensional
      constructive interference in steady state, 3-dimensional magnetization-prepared
      rapid gradient echo and T2-weighted 2-dimensional turbo spin echo magnetic
      resonance imaging sequences.
AB  - OBJECTIVE: The purpose of this study was to evaluate the visibility of the IXth
      to XIIth cranial nerves using different magnetic resonance sequences. Thirty
      healthy volunteers underwent magnetic resonance imaging at 1.5 T using 3
      dimensional constructive interference in steady state (CISS) sequence (TR = 17
      ms, TE = 8.08 ms, alpha = 70 degrees), 3-dimensional magnetization-prepared rapid
      gradient echo (MP-RAGE) sequence (TR = 11.08 ms, TE = 4.3 ms, alpha = 15
      degrees), and T2-weighted (w) 2-dimensional turbo spin echo (TSE) sequence (TR =
      4000 ms, TE = 102 ms, alpha = 180 degrees, slice thickness = 2 mm). Visibility of
      the IXth to XIIth cranial nerves in each sequence was evaluated by consensus of 2
      radiologists using an evaluation scale from 1 (excellently visible) to 5 (not
      visible). A correlation with anatomic specimens was made. The 3-dimensional CISS
      sequence provides best resolution of the IXth to XIIth cranial nerves and their
      relation to surrounding structures. Additional information is given by the 3
      dimensional MP-RAGE when nerves are surrounded by soft tissues. Using the T2w 2
      dimensional TSE sequence, even whole nerves cannot be visualized due to
      intersection gap and partial volume effects. However, even in 3-dimensional high
      resolution sequences, segments of nerves are not always visualized. A combination
      of 3-dimensional CISS and 3-dimensional MP-RAGE proved to be useful to visualize
      the IXth to XIIth cranial nerves, whereas the 2-dimensional technique failed.
      Further investigations using 3-dimensional MP-RAGE with contrast medium should be
      performed in the case of abnormality.

PMID- 11296587
TI  - Differences in functional magnetic resonance imaging activation by category in a
      visual confrontation naming task.
AB  - OBJECTIVE: Cortical processing involved in seemingly similar tasks may differ in
      important ways. The authors mapped cortical regions engaged in a commonly
      performed picture naming task, seeking differences by semantic category.
      Functional magnetic resonance imaging was used during presentation of
      standardized line drawings in 18 healthy right-handed female participants,
      comparing living versus nonliving entities. During visual naming, across
      categories there was strong activation of left frontal (BA45/47), bilateral
      temporo-occipital junction (BA19), and inferior temporal regions (BA36/37).
      Activation of right inferior temporal cortex (BA19 and BA37) was greater during
      naming of living versus nonliving category items. No category differences in
      activation strength in the left temporal lobe were observed. The authors conclude
      that visual semantic operations may involve visual association cortex in the
      right temporal lobe in women.

PMID- 11296588
TI  - Cerebral hemodynamics changes during retrograde brain perfusion in dogs.
AB  - The objective of this study was to examine cerebral hemodynamics changes during
      hypothermic circulatory arrest (HCA) with and without retrograde cerebral
      perfusion (RCP). Thirteen colony-bred hound dogs were placed on cardiopulmonary
      bypass (CPB) and cooled to 18 degrees C. Five dogs underwent 2 hours of HCA
      without RCP and 8 with RCP. The animals were then rewarmed on CPB until
      normothermic and weaned. Cerebral blood flow velocity (CBFV) and Gosling
      Pulsatility Index (PI) in the middle cerebral artery (MCA) were studied using
      trans-cranial Doppler ultrasound (TCD). At baseline and during pre- and
      postarrest CPB, there was anterograde direction of blood flow in the MCA. During
      HCA with RCP, there was retrograde direction of blood flow in the MCA. There was
      no difference in CBFV between pre-, during, and postarrest CPB in the group with
      RCP; however, there was significantly increased CBFV during postarrest CPB in the
      group without RCP compared to the dogs with RCP. Later, at 3 hours after
      postarrest CPB, there was decreased CBFV in all animals accompanied by increased
      PI (2.4 +/- 0.4 and 2.2 +/- 0.6 for animals with RCP and without RCP,
      respectively) and abnormal TCD waveform changes including decreased diastolic
      compartment and sharp systolic peak. During hypothermic circulatory arrest, RCP
      provides CBFV in the MCA comparable to MCA CBFV during CPB. HCA dogs without RCP
      showed immediate hyperemia on reperfusion. The decreased CBFV and increased PI at
      1 hour after postarrest CPB could be an indicator of progressive ischemic injury
      due to the increased intracranial pressure despite the implementation of RCP.

PMID- 11296589
TI  - Effect of hyperventilation on cerebral blood flow velocity in preeclamptic
      pregnancies: is there evidence for an altered cerebral vasoreactivity?
AB  - The purpose of this study was to investigate cerebral arteriolar vasoreactivity
      function in preeclampsia. Preeclamptic (n = 26) and healthy pregnant (n = 22)
      women underwent transcranial Doppler sonography of the middle cerebral artery at
      rest and after 60 seconds of hyperventilation (HV). Systolic, diastolic, and mean
      blood flow velocities were recorded. The percentage change of the blood flow
      velocities after HV was calculated. Mean blood flow velocity of the middle
      cerebral artery was higher in preeclamptic women as compared with healthy
      pregnant women. No difference could be detected in percentage change of middle
      cerebral artery blood flow velocities after HV between the two groups. There is
      no evidence of a small-vessel vasoconstriction among preeclamptic patients. The
      role of vasoconstriction of the large cerebral arteries and vasodilation of the
      resistance arterioles, as well as a combination of these 2 pathomechanisms, in
      determining cerebral blood flow in preeclampsia and eclampsia should be
      investigated in further studies.

PMID- 11296591
TI  - Isolated petrous carotid stenosis and transient ischemic attack.
AB  - Although anterior circulation transient ischemic attacks (TIAs) tend to be more
      common in patients with extra- cranial carotid arterial disease than in those
      with intracranial carotid or middle cerebral arterial disease, the authors
      recently encountered 4 patients with both recurrent, stereotypical TIAs as well
      as isolated stenosis of their petrous internal carotid artery (ICA). While the
      gold standard for establishing the diagnosis of intracranial large-artery disease
      has always been conventional angiography, magnetic resonance angiography changes,
      confirmed with intra-arterial digital subtraction angiography in 2 of these
      patients, were quite sufficient to define the occlusive disease in each of the
      cases. Petrous ICA stenosis is not uncommon, but it has often been overshadowed
      by the search for extracranial ICA disease that might be amenable to surgical
      reconstruction.

PMID- 11296590
TI  - Early computed tomography hypodensity predicts hemorrhage after intravenous
      tissue plasminogen activator in acute ischemic stroke.
AB  - Parenchymal hypodensity is a proposed risk factor for hemorrhage after
      recombinant tissue plasminogen activator (TPA) thrombolysis for ischemic stroke.
      In Buffalo, NY, and Houston, TX, the authors reviewed 70 patients who were
      treated with intravenous TPA for acute middle cerebral artery (MCA) stroke. Two
      observers blinded to clinical outcome analyzed initial noncontrast head computed
      tomography (CT) scans. Basal ganglia CT hypodensity was quantitated in Hounsfield
      units (HUs). Contralateral-ipsilateral difference in density was calculated using
      the asymptomatic side as a control. Ictus time to TPA averaged 2.5 hours. Six
      patients developed symptomatic intraparenchymal hematomas (2 fatal). The
      hemorrhage group had more severe basal ganglia hypodensity (mean 7.5 +/- 1.4,
      range 6-10 HU) than the nonhemorrhage group (2.2 +/- 1.4, range 0-9 HU) (P <
      .0001). The hemorrhage group had hypodensity of > 5 HU; the nonhemorrhage group
      had hypodensity of < or = 4 HU, except 1 patient with hypodensity of 9 HU. In
      predicting hemorrhage, the positive predictive value of hypodensity > 5 HU was
      86%; the negative predictive value was 100%. Prethrombolysis NIH Stroke Scale
      (NIHSS) deficit (P = .0007) and blood glucose (P = .005) were also higher in the
      hemorrhage group. Age, gender, smoking, hypertension, and ictus time to TPA
      infusion did not differ between the 2 groups. Logistic regression indicated that
      basal ganglia hypodensity was the best single predictor of hemorrhage.
      Hypodensity and NIHSS score together predicted all cases of hemorrhage. The
      authors conclude that basal ganglia hypodensity quantified by CT may be a useful
      method of risk stratification to select acute MCA stroke patients for
      thrombolytic therapy.

PMID- 11296592
TI  - Reproducibility of proton magnetic resonance spectroscopy imaging measurements of
      normal human hippocampus at 1.5 T: clinical implications.
AB  - The authors investigate the reproducibility of metabolite signals measured with
      proton magnetic resonance spectroscopy (1H-MRS) acquired from the human
      hippocampus in controls and in a phantom. Two 1H-MRS studies separated by 3 weeks
      were performed in 8 healthy volunteers and in a phantom. N-acetyl compounds (NA),
      choline (Ch), and creatine (Cr) peak areas and ratios were measured and compared
      using percentage variation, and Pearson Correlation Coefficient at the level of
      every voxel, the level of 1 hippocampus (5 voxels), and the level of 2 hippocampi
      (10 voxels). Sensitivity for observing clinically significant between-session 1H
      MRS changes was evaluated using the reliable change index. Reproducibility
      measures for metabolite peak areas were only moderately concordant with
      percentage variation ranging from 14% to 20% for NA, Cho, and Cr. Stability was
      much improved when NA ratios and sum of multiple voxels were considered. Between
      session NA/(Cho + Cr) changes greater than 22%, 12%, and 10% in one given
      participant can be detected with a 90% confidence interval when considered at the
      single-voxel level, the level of a single hippocampus, or the level of both
      hippocampi, respectively. Left-right asymmetry indices showed similar and limited
      inter-hemispheric asymmetry in repeated examination. This study suggests that 1H
      MRS reproducibility performance is adequate for the study and monitoring of human
      hippocampus function when NA ratios and the sum of multiple voxels are
      considered. Individual metabolite peaks and single-voxel measurements have low
      reproducibility at 1.5 T and should be used only with clearly established
      statistical parameters.

PMID- 11296593
TI  - Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use
      of reductase inhibitors for intracranial plaque stabilization.
AB  - Regression of symptomatic intracranial atherostenosis is not known to be a common
      occurrence. In this case, delay of basilar reconstruction by endovascular means
      permitted serial angiographic assessment of plaque change. The use of high-dose
      atorvastatin over a 2-week period was associated with marked angiographic
      improvement. Medical programs of plaque stabilization may provide adjunctive
      benefit in patients with symptomatic intracranial disease.

PMID- 11296594
TI  - Transcranial color-coded sonography of a vein of Galen arteriovenous malformation
      in an adult.
AB  - The case of an adult harboring a vein of Galen arteriovenous malformation (VGAM)
      is reported. Diagnosis was established by computed tomography (CT) and digital
      subtraction angiography and confirmed afterwards by transcranial color-coded
      sonography (TCCS). The patient's course after endovascular treatment was then
      consecutively monitored by TCCS until complete occlusion was achieved. The
      results of TCCS were validated by angiography, with which they showed good
      correlation. Thus, it can be concluded that TCCS may be a useful adjunct to CT
      and angiography to noninvasively monitor adults with VGAM.

PMID- 11296595
TI  - In vivo 1H magnetic resonance spectroscopic measurement of brain glycine levels
      in nonketotic hyperglycinemia.
AB  - Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder of glycine
      metabolism. Defective glycine cleavage causes elevated concentrations of glycine
      in plasma, urine, and cerebrospinal fluid. A longitudinal study using magnetic
      resonance imaging (MRI) and single-voxel 1H magnetic resonance spectroscopy (MRS)
      was performed on an infant with the typical clinical picture of NKH. He was
      examined twice during the course of treatment with sodium benzoate and
      dextromethorphan. At the age of 10 months, MRI showed normal brain structure,
      while MRS detected a prominent glycine peak in the brain. Repeat MRS at the age
      of 13 months showed a small increase in glycine peak and a prominent
      glutamate/glutamine peak not previously detected. The MRS measurements were
      consistent with the slight increase in blood glycine level and the elevation in
      glutamine level, indicating that 1HMRS can be a valuable tool in the diagnosis
      and monitoring of treatment effects in patients with NKH.

PMID- 11296596
TI  - HIV-2 infection with cerebral toxoplasmosis and lymphomatoid granulomatosis.
AB  - A Nigerian man had acute onset of headache and vertigo due to a cerebellar mass.
      A brain biopsy of the mass revealed toxoplasmosis despite repeated negative HIV-1
      serology. The presence of an opportunistic infection and his country of origin
      raised the suspicion for HIV-2; this was confirmed by positive HIV-2 serology.
      Despite his preliminary pathological diagnosis, results of physiological magnetic
      resonance imaging (MRI) (perfusion MRI and proton magnetic resonance
      spectroscopy) were not typical for toxoplasmosis. The lesion showed a biochemical
      and perfusion pattern that was intermediate for infectious and neoplastic
      processes. Further neuropathology confirmed a secondary diagnosis of lymphomatoid
      granulomatosis.

PMID- 11296598
TI  - Coping with work-force shortage requires creative recruitment and more.

PMID- 11296597
TI  - PBMs act to boost e-prescribing.

PMID- 11296599
TI  - Health care system needs overhaul, IOM report says.

PMID- 11296600
TI  - Long-acting asthma medication, new inhaler approved by FDA.

PMID- 11296601
TI  - New type of antifungal approved for invasive aspergillosis.

PMID- 11296602
TI  - Early reports on Iowa pharmaceutical case management seem encouraging.

PMID- 11296603
TI  - Learning from errors begins with reporting them.

PMID- 11296604
TI  - Evaluation of studies investigating the effectiveness of pharmacists' clinical
      services.
AB  - A quantitative evaluation of randomized trials of counseling, education, and
      other clinical services provided by pharmacists was performed. Data sources were
      MEDLINE and the bibliographies of published articles. Pharmacists' services were
      categorized as counseling of patients, counseling of physicians, counseling of
      both patients and physicians, and patient care. The outcomes extracted were
      measures of patient behavior, disease, symptoms, and patient knowledge. Thirty
      two trials met the inclusion criteria. The pharmacists were specified as clinical
      pharmacists in 24 trials and as community pharmacists in 2. In six unblinded
      trials of patient counseling, the outcomes favored the counseled patients over
      control patients in every trial, and the effects were statistically significant
      in five trials (the outcome was medication adherence in these five trials). In
      seven trials of counseling of both patients and their physicians, patient
      outcomes were significantly better in the intervention group in six trials, four
      of which were single blind. Two trials in which patients were randomized to
      either physician counseling or control groups yielded inconsistent results. In
      one trial in which physicians were randomized to receive counseling from
      pharmacists, the proportion of prescriptions meeting guidelines was higher in the
      counseling group than in the control group. Four trials of patient care by
      pharmacists were inconclusive. These trials demonstrated that counseling of
      patients and their physicians by pharmacists can improve patient outcomes. The
      evidence that counseling of patients alone improved patient outcomes was good,
      though weaker because of suboptimal trial design.

PMID- 11296605
TI  - Stability of norfloxacin in an extemporaneously prepared oral liquid.
AB  - The stability of norfloxacin in an extemporaneously prepared suspension stored at
      room temperature and under refrigeration was studied over 56 days. A 20-mg/mL
      suspension was prepared from commercially available 400-mg norfloxacin tablets
      and equal amounts of Ora-Plus and strawberry syrup to make a final volume of 60
      mL. Six identical samples of the suspension were prepared in amber plastic
      prescription bottles. Three were stored at room temperature (23-25 degrees C) and
      three under refrigeration (3-5 degrees C). Immediately after preparation and at
      7, 14, 28, and 56 days, the samples were assayed in duplicate by stability
      indicating high performance liquid chromatography. The samples were also
      inspected for color and odor changes and the pH of each sample was determined. At
      least 93% of the initial norfloxacin concentration remained throughout the 56-day
      study period. The color, odor, and pH of all of the samples did not change
      appreciably. An extemporaneously prepared suspension of norfloxacin 20 mg/mL was
      stable for at least 56 days when stored at either 23-25 or 3-5 degrees C.

PMID- 11296606
TI  - Dose variance associated with calibration and administration of
      radiopharmaceuticals.
AB  - Variation in the amounts of radioactivity that is associated with dose
      calibration and administration of gamma-emitting radioactive drugs was studied.
      Health systems use radionuclide dose calibrators when they need to assay drugs
      for radioactivity. However, the radioactive drugs commonly used for therapeutic
      or diagnostic purposes are compounded and assayed in or administered from
      containers that differ from those containing the standard reference materials
      (SRMs). SRMs for four radionuclides--technetium 99m, indium 111, thallium 201,
      and iodine 131--were drawn up into vials and syringe-needle assemblies of volumes
      and sizes represented in clinical practice. In each sample, the amount of
      radioactivity was calculated and compared with values obtained from three dose
      calibrators. In addition, over a four-month period, 101 samples of technetium Tc
      99m medronate injection with a desired activity of 20 mCi were prepared in
      syringes; the radioactive dose in each syringe was calibrated for administration
      to a patient at a specific time that day. The amounts of radioactivity at the
      time of preparation and the time of administration, the amount remaining in the
      syringe and needle after administration, and the amount reported as administered
      were recorded. Measurement with the dose calibrators of the SRMs in containers
      supplied by the National Institute of Standards and Technology showed
      radioactivity within 10% of the labeled amount, the percentage of variation
      regulations allow. Measurements of the SRMs in syringe-needle assemblies were
      within 10% for technetium 99m and thallium 201, 9-16% for iodine 131, and 15-26%
      for indium 111. The individual doses of technetium 99m medronate injection were,
      on average, administered on time, but doses were administered up to 75 minutes
      before and 107 minutes after the calibration time. The mean +/- S.D. amount
      administered was 19.0 +/- 1.34 mCi. The mean +/- S.D. amount reported
      administered was 20 +/- 0.24 mCi. How radiopharmaceuticals were dose calibrated
      and administered influenced the actual dose available to patients.

PMID- 11296607
TI  - Compatibility of spacers with metered-dose inhalers.

PMID- 11296608
TI  - HIV pharmacy specialty residency program in Canada.

PMID- 11296609
TI  - Compatibility and stability of vincristine sulfate, doxorubicin hydrochloride,
      and etoposide phosphate in 0.9% sodium chloride injection.

PMID- 11296611
TI  - ASHP policy recommendations--invitation to comment.

PMID- 11296610
TI  - Promoting the use of oral ondansetron in children receiving cancer chemotherapy.

PMID- 11296612
TI  - Treatment of hyperlipidemia in HIV-infected patients.
AB  - The treatment of hyperlipidemia in patients infected with HIV is discussed.
      Hyperlipidemia is common in HIV-infected patients receiving antiretroviral
      therapy, especially protease inhibitors and stavudine. The recommendations of the
      National Cholesterol Education Program (NCEP) may not entirely apply to HIV
      infected patients. The pathogenesis of hyperlipidemia in these patients may make
      them refractory to traditional pharmacotherapy, and NCEP's emphasis on diet and
      exercise may be unrealistic. Other factors that may complicate treatment of
      hyperlipidemia include metabolism of many antiretroviral drugs by the cytochrome
      P-450 isoenzyme system, polypharmacy, and drug-food interactions. A patient's
      cardiac risk should first be assessed. Nonpharmacologic measures, such as a low
      fat diet, weight reduction, and exercise, should be considered. Drug therapy is
      indicated for patients with familial combined hyperlipidemia that is associated
      with atherogenesis and for patients with triglyceride concentrations exceeding
      1000 mg/dL. Drug therapy for hyperlipidemia involves niacin and statins, in
      addition to fibric acid derivatives and probucol. Switching among antiretroviral
      agents when one is found to cause hyperlipidemia should be done cautiously
      because of the risk for viral rebound and disease progression. NCEP guidelines
      recommend monitoring low-density-lipoprotein cholesterol levels four to six weeks
      after the start of lipid-lowering therapy and then at three months; more frequent
      monitoring may be necessary in HIV-infected patients. The treatment of
      hyperlipidemia in HIV-infected patients is complicated by their need for
      antiretroviral drugs, which can themselves contribute to lipid disorders.

PMID- 11296613
TI  - Equivalence of generic and brand-name ophthalmic products.

PMID- 11296614
TI  - Alteplase activity.

PMID- 11296615
TI  - Economic analysis of amifostine as adjunctive support for patients with advanced
      head and neck cancer: preliminary results from a randomized phase II clinical
      trial from Germany.
AB  - In a randomized phase II trial in Germany, we investigated the clinical and
      economic impact of amifostine protection against the hematological and oral
      toxicities of carboplatin administered concurrently with standard fractions of
      radiotherapy. 28 patients with squamous cell carcinomas of the head and neck
      received adjunctive or primary radiotherapy (5 days per week with daily fractions
      of 2 Gy, up to a total dose of 60 Gy) in conjunction with carboplatin (70 mg/m2)
      on days 1-5 and days 21-26. All patients received radiation encompassing at least
      75% of the major salivary glands. Patients were randomized to receive radiation
      and carboplatin (RCT) alone or RCT preceded by rapid infusion of amifostine (500
      mg) on days carboplatin was administered. The 14 patients who received
      amifostine, in comparison to 14 patients in the control arm, had significantly
      fewer episodes of grade 3 or 4 thrombocytopenia (p = 0.001), mucositis (p =
      0.001), and xerostomia (p = 0.001). The patients receiving amifostine accrued
      significantly lower supportive care costs for resources related to infection
      ($241 vs. $1,275, p < 0.01), red blood cell and platelet support ($286 vs. $1,276
      p = 0.06) alimentation ($343 vs. $894, p = .01), and hospitalization ($286 vs.
      $2,429, p < 0.01). Overall, including the costs of amifostine, mean per patient
      supportive care costs were $4,401 for the amifostine group and $5,873 (p = .02)
      for the control group. Our results from a randomized phase II trial indicate that
      selective cytoprotection with amifostine potentially offers clinical and economic
      benefits in patients with advanced head and neck cancer receiving
      radiochemotherapy. Additional economic studies alongside randomized phase III
      trials and from other countries are needed.

PMID- 11296616
TI  - Evidence for stimulation of tumor proliferation in cell lines and histotypic
      cultures by clinically relevant low doses of the galactoside-binding mistletoe
      lectin, a component of proprietary extracts.
AB  - The toxic galactoside-specific lectin from mistletoe, a component of proprietary
      extracts with unproven efficacy in oncology, exhibits capacity to trigger
      enhanced secretion of proinflammatory cytokines at low doses (ng/ml or ng/kg body
      weight) and reductions of cell viability with increasing concentrations. To infer
      any tumor selectivity of this activity, cytofluorimetric and cell growth assays
      with a variety of established human tumor cell lines were performed. Only
      quantitative changes were apparent, and the toxicity against tumor cells was
      within the range of that of the tested fibroblast preparations from 5 donors. No
      indication for any tumor selectivity was observed. In kinetic studies with 8
      sarcoma and 4 melanoma lines, this evidence for quantitative variability of the
      response in interindividual comparison was further underscored. At 50 pg
      lectin/ml x 10(5) cells, even a growth-stimulatory impact was noted in 5 of 12
      tested cases. To mimic in vivo conditions with presence of cytokine-secreting
      inflammatory and stromal cells, exposure to the lectin was extended to histotypic
      cultures established from 30 cases of surgically removed tumor. As salient
      result, 5 specimens from 4 of the 8 tested tumor classes responded with a
      significant increase of [3H]-thymidine incorporation relative to controls during
      the culture period of 72 hours, when the lectin was present at a concentration in
      the described immunomodulatory range (1 ng/ml). A relation of this activity to
      the extent of the actual proliferative status of the reactive samples could not
      be delineated. Therefore, a non-negligible percentage of the established tumor
      cell lines (e.g., 3 from 8 sarcoma lines) can be markedly stimulated by the
      lectin at a very low dose and with dependence on the cell type. Furthermore, the
      feasibility to elicit a significant growth enhancement is likewise documented for
      human tumor explants in 16.6% of the examined cases. In view of the uncontrolled
      application of lectin-containing extracts in alternative/complementary medicine,
      the presented results on unquestionably adverse lectin-dependent effects in two
      culture systems call for rigorous examination of the clinical safety of this
      unconventional, scientifically entirely experimental treatment modality.

PMID- 11296617
TI  - Long-term follow-up on an intensified treatment regimen for advanced resectable
      head and neck squamous cell carcinomas.
AB  - From February 1993 through July 1994, 37 patients with stage III-IV squamous cell
      carcinomas of the oral cavity, oropharynx, or hypopharynx (stage II-IV) were
      registered to a treatment regimen consisting of preoperative continuous infusion
      cisplatin (80 mg/m2/80 hours) with hyperfractionated external beam radiotherapy
      (9.1 Gy/7 fractions of 1.3 Gy BID), surgical resection, intraoperative
      radiotherapy (7.5 Gy), and postoperative radiotherapy (40 Gy) with concurrent
      cisplatin (100 mg/m2 x 2 courses). The objectives of the regimen were to improve
      patient compliance while also increasing treatment intensity. The purpose of this
      article is to report the local, regional (nodal), and distant disease control of
      these patients after an extended time at risk (median 40 months). Overall
      compliance (73%), local control at primary site (97%), and regional nodal control
      (95%) were excellent. The rate of distant metastasis was 19%. Absolute survival
      at 48 months was 45.9%.

PMID- 11296618
TI  - Dose-dense sequential chemotherapy with epirubicin and paclitaxel in advanced
      breast cancer.
AB  - The purpose of this study was to evaluate the activity and toxicity profile of
      dose-dense sequential chemotherapy with epirubicin (EPI) and paclitaxel in
      advanced breast cancer (ABC). From January to September 1997, 41 patients with
      recurrent or metastatic (stage IV) breast cancer were enrolled in the study.
      Their median age was 57 (range, 33-77) years and median performance status 0
      (range, 0-2). Twenty patients had received adjuvant chemotherapy. The
      chemotherapeutic regimen consisted of 4 cycles of EPI 110 mg/m2 every 2 weeks
      followed by 4 cycles of paclitaxel, 225 mg/m2 over 3 hours every 2 weeks. G-CSF
      was administered prophylactically on days 2-10 of each cycle. 34 (83.0%) patients
      completed all 8 cycles of chemotherapy. A total of 304 cycles were administered,
      259 (85.0%) of them at full dose. Thirty (10.0%) cycles were delivered with a
      delay. The relative median dose intensities of EPI and paclitaxel were 0.95. Most
      common grade 3-4 side effects were anemia (15.0%) neutropenia (12.0%),
      thrombocytopenia (5.0%), nausea/vomiting (10.0%), febrile neutropenia (7.5%), and
      alopecia (90.0%). Overall, 8 (19.5%) patients achieved a complete and 15 (36.5%)
      a partial response. Median duration of response was 8.4 (range, 3.1-15.5+)
      months. After a median follow-up of 18.5 months, median time to progression was
      8.7 (range, 0.5-21+) months; median survival has not been reached yet. Dose-dense
      sequential chemotherapy with EPI and paclitaxel shows promising activity as first
      line treatment in ABC. Randomized studies comparing this type of chemotherapy
      with the classical administration of the two drugs together every 3 weeks are
      ongoing.

PMID- 11296619
TI  - 4-(N-hydroxyphenyl)retinamide can selectively induce apoptosis in human
      epidermoid carcinoma cells but not in normal dermal fibroblasts.
AB  - The retinoid 4-(N-hydroxyphenyl)retinamide (4HPR, fenretinide) has both growth
      inhibitory and apoptosis-inducing effects on a number of cancer cell lines in
      vitro and in vivo and has been entered into a number of oncological trials.
      However, little is known about its mechanism(s) of action or its effects on
      normal cells such as fibroblasts. In this study, the effects of fenretinide on
      both epidermoid carcinoma cells of vulva (cell line A431) and normal human dermal
      fibroblasts, both as monolayers and also grown in 3D cell culture systems, have
      been investigated. The 3D cell culture system contained normal human fibroblasts
      embedded in a type I collagen gel with the carcinoma cells seeded on top of the
      collagen gel, which mimics the epidermoid carcinoma. Fenretinide significantly
      inhibited the rate of DNA synthesis of carcinoma cells, while there was little
      effect on fibroblasts on monolayers, at 10(-6)-10(-5) M, which are clinically
      attainable doses. Fenretinide at 5 x 10(-6) M induced apoptosis characterised by
      cell shrinkage, membrane blebbing, nuclear condensation and/or fragmentation, and
      cell detachment in carcinoma cells, but not fibroblasts from monolayers.
      Fenretinide also reduced the viability of carcinoma cells in the 3D cell culture
      system without affecting fibroblasts. These data show that fenretinide may
      preferentially induce apoptosis in epidermoid carcinoma cells.

PMID- 11296620
TI  - Doxorubicin and paclitaxel in the treatment of advanced breast cancer: efficacy
      and cardiac considerations.
AB  - Doxorubicin and paclitaxel are highly active agents in the treatment of advanced
      breast cancer. Although early trials of the combination reported high response
      rates, an unexpectedly high incidence of congestive heart failure observed on two
      of the early trials was cause for much concern. More recently, clinical trials
      that have limited the cumulative doxorubicin dose to 400 mg/m2 or below when
      given in combination with paclitaxel have not observed an increase in cardiac
      toxicity. In addition, a retrospective review of over 600 women with advanced
      breast cancer treated with doxorubicin and paclitaxel concluded that the
      combination could be administered safely up to a cumulative doxorubicin dose of
      340-380 mg/m2. It is likely that a pharmacokinetic interaction between
      doxorubicin and paclitaxel is, in large part, responsible for the higher than
      expected incidence of congestive heart failure observed in some studies. It
      appears that paclitaxel decreases the clearance of doxorubicin by approximately
      30% when the two drugs are administered in close succession. Because the use of
      combination of doxorubicin and paclitaxel may benefit women with advanced breast
      cancer, a review of pertinent clinical studies and the implications of the
      pharmacokinetic interaction is provided. Particular attention has been paid to
      cardiac toxicities. It can be concluded that the use of combination doxorubicin
      and paclitaxel is safe up to a cumulative doxorubicin dose of 340-380 mg/m2. This
      would allow for up to six courses of therapy with doxorubicin 60 mg/m2 and
      paclitaxel 175 mg/m2 by 3-hour infusion. Therapy can be continued with single
      agent paclitaxel. In order to minimize cardiac risk, patients should be selected
      carefully and be monitored for adverse cardiac effects.

PMID- 11296621
TI  - Determinants of place of death for terminal cancer patients.
AB  - Approximately two-third of cancer patients, when asked about the preferred place
      of death, wish to die in their own homes. However, the majority of deaths from
      cancers in most western countries occur in a hospital. When a person dies from
      other than sudden or traumatic causes, the death appears to be a function of a
      complex interplay of personal and cultural values and physical and medical
      factors, as well as various health care systems forces. This article reviews the
      determinants of place of death for terminal cancer patients from published
      studies in hopes of shedding light on the difficulties of dying patients to
      realize their preferences for place of death. These insights may contribute to
      modification of hospice care systems so health professionals will be more
      responsive to the needs of their dying patients to retain control and die with
      dignity and help health professionals achieve the proposed outcome of hospice
      care.

PMID- 11296622
TI  - Role of angiogenesis in the progression and treatment of prostate cancer.

PMID- 11296623
TI  - The role of inadequate health literacy skills in colorectal cancer screening.
AB  - Colorectal cancer is ideally suited for early detection strategies that are
      likely to improve survival rates. Screening with either a fecal occult blood test
      (FOBT) or flexible sigmoidoscopy has been shown to identify precancerous polyps
      or cancers in early stages. However, persons with limited education and of lower
      socioeconomic status infrequently participate in screening programs in general
      and have very low rates of colorectal screening. Low literacy, which is common
      among persons with limited education and low income, may be an overlooked factor
      in understanding patients' decision making about colorectal cancer screening.
      This article provides information from focus groups about colorectal cancer
      screening, which we examine in the context of relevant literature on cancer
      screening and literacy. Using the health belief model, we examine the association
      between inadequate health literacy skills and low rates of colorectal cancer
      screening. The theoretical model also provides insights into strategies for
      improving knowledge, attitudes, and beliefs and screening rates for this
      challenging patient population.

PMID- 11296624
TI  - Development of QSAR models to predict estrogenic, carcinogenic, and cancer
      protective effects of phytoestrogens.
AB  - An integrated QSAR model has been formulated to predict estrogenic, carcinogenic,
      and cancer protective effects of phytoestrogens (PE). Relative binding of PEs to
      estrogen receptors ER alpha and ER beta exhibited a parabolic relationship with
      dipole moment (mu). The high-affinity binding of PEs to ER alpha correlated with
      Dif0 (0 chi-0 chi v difference index encoding nonsigma electronic charge), while
      the low-affinity binding of PEs to ER alpha correlated with H bonding (positive
      coefficient) and % hydrophilic surface (negative coefficient). The high-affinity
      binding of PEs to ER beta correlated with molecular with (MWd) and Dif0, while
      the low-affinity binding of PEs to ER beta correlated with H bonding (positive
      coefficient) and hydrophilic-lipophilic balance (negative coefficient). Thus an
      increase in electronic or ionic charge, formation of H bonds, or a decrease in
      hydrophilic property of PEs may increase their binding to ER. The relative
      transcription activity (RTA) of ER alpha correlated with Dif0-Dif1, while RTA of
      ER beta correlated with H bonding and polarity. The PE-induced stimulation of DNA
      synthesis in estrogen-sensitive breast cancer (BC) cells correlated positively
      with (MD*4 chi v) where MD is molecular depth and 4 chi v is the valence of a 4th
      order fragment. IC50 for PE-induced inhibition of DNA synthesis in estrogen
      sensitive BC cells correlated with (MD*Log P) and Dif3 (3 chi-3 chi v difference
      index encoding nonsigma electronic charge of fragments consisting of four atoms
      and three bonds) and Dif3(2). IC50 for PE-induced inhibition of DNA synthesis in
      estrogen-independent cancer cell lines correlated with (MD*Log P) and 1/water
      solubility. Thus molecular shape and molecular connectivity of PEs play a key
      role in modulating estrogen-induced transactivation activity and DNA synthesis in
      BC cells.

PMID- 11296625
TI  - A new intensified therapeutic regimen for advanced head and neck squamous cell
      carcinomas: where does it fit among available treatment options?

PMID- 11296626
TI  - Managed care and medical oncology.

PMID- 11296627
TI  - [Consultation skills in urology: a model for teaching and evaluation].
AB  - OBJECTIVE: Consultation activity is an important aspect of urological practice,
      but the specific teaching of this activity is underdeveloped. The objective of
      this study was to establish a list of consultancy skills as a basis for a planned
      and structured approach to teaching and evaluation of consultancy skills in
      urology. MATERIAL AND METHOD: Two-step qualitative protocol: 1) Establishment of
      an initial list of skills based on data of the literature; 2) Submission of this
      list to a series of "focus groups" (urologists, interns, referring physicians) in
      order to validate and progressively refine the model. RESULTS: The items
      identified were classified into 3 distinct lists: 1) theoretical knowledge; 2)
      technical skills specific to urology, predominantly performed in the consulting
      setting, 3) interpersonal skills exclusively concerning the consultant-referring
      physician relationship. CONCLUSIONS: The consensual specification of these skills
      can be used to objectively define teaching and evaluation strategies for urology
      consultancy skills.

PMID- 11296628
TI  - [Obstetrical vesico-vaginal fistula. Report of 114 cases].
AB  - OBJECTIVE: Obstetric vesico-vaginal fistulas are frequent in North Africa. The
      objective of this paper is to analyse the epidemiologic and therapeutic factors,
      basing our study on 114 cases of vesico-vaginal fistulas. METHODS: From February
      1989 to December 1998, 114 patients with a mean age of 33 years (range: 17 to 76
      years) were admitted to the department of urology for urogenital fistulas,
      classified as a function of the site of the fistula into 3 types, according to
      Benchekroun's classification: type I: urethrovaginal fistula (39.96%); type II:
      cervicovaginal fistula (11.40%); type III: vesicovaginal fistula (52.63%).
      Investigation of each patient comprised complete physical examination with
      laboratory and radiological assessment. Treatment was only performed after a
      minimal period of 3 months. RESULTS: The majority of fistulas occurred in young
      multiparous women living in rural zones, predominantly due to an obstetric
      aetiology (87%). 183 reconstructive operations were performed in 114 patients,
      i.e. 1.73 operations per patient. Cure was obtained in 87 patients (76.3%) with
      37% for type I, 92% for type II and 100% for type III. Twelve intermediate
      results (fistulas were closed, with persistent stress incontinence or frequency)
      and 16 failures (persistence of a residual fistula or need for urinary diversion)
      all concerned type I fistulas. CONCLUSION: It appears that VVFs represent a
      public health problem in North Africa and that their surgical treatment is still
      technically difficult.

PMID- 11296629
TI  - [Update on kidney tumors in children: role of the pediatric surgeon].
AB  - The surgical treatment of malignant renal tumours in children (nephroblastomas)
      is part of a multimodal therapeutic strategy, defined by the International
      Society of Paediatric Oncology protocol. Resection of the primary tumour and
      determination of the post-operative stage determine subsequent treatment. The
      modalities of the surgical procedure are described together with the particular
      cases concerning infants under the age of 6 months, extension to the renal vein
      and inferior vena cava, emergency surgery, bilateral, tumours or tumour in a
      solitary kidney, lymph node involvement, metastatic nephroblastomas and
      complications of surgery.

PMID- 11296630
TI  - [Uretero-vesical implantation after failure of endoscopic treatment of reflux:
      anatomical and histological study of 61 resection specimens from 40 children].
AB  - OBJECTIVE: To evaluate the anatomy and histology of the ureterovesical junction
      resected during secondary surgical reimplantation for persistent reflux after
      failure of initial endoscopic treatment by polytetrafluoroethylene (Teflon) in 27
      cases and polydimethylsiloxane (Macroplastique) in 13 cases. MATERIAL AND METHOD:
      61 ureterovesical junctions from 40 children were studied histologically. The
      mean age of the patients at the time of the operation was 4.1 years (range: 1 to
      15 years). The mean interval between endoscopic injection and surgical
      reimplantation was 15.3 months (range: 2 to 54 months). RESULTS: Persistent
      reflux was not correlated with the anatomical situation of the implant, which was
      found to be in a satisfactory position in 52.4% of cases. Both of the substances
      used induced a giant-cell macrophage reaction which colonized the implant and
      triggered new vessel formation. Macroplastique appeared to be associated with a
      more intense inflammatory reaction than Teflon. Despite the difference in
      particle size, the two substances induced a macrophage phenomenon characterized
      by microfragmentation into 6 micron particles. No conclusions can be drawn
      concerning distant migration, but this study showed rarefaction of particles
      which were replaced by fibrosis, the density of which was correlated with the age
      of the implant. CONCLUSION: Extinction of the local reaction induced by the
      products used in this study appears to be long and the end of this process is
      unknown, which justifies prolonged surveillance of children treated for reflux by
      endoscopic submeatal injection.

PMID- 11296631
TI  - [Dangers of sub-group analysis and of multiple tests].
AB  - Subgroup analyses, "retrospective" statistics, and multiple tests, motivated by
      the search for explanatory covariables, are frequently used in the medical
      literature. However, these data manipulations induce modifications of the groups
      defined by initial randomization, an unverifiable increase of the alpha risk, a
      reduction of the power of the study and a risk of circular reasoning. Taking the
      example of an article concerning the hormonal treatment of prostate cancer,
      several situations are discussed, according to whether or not the study is
      prospective, whether or not the covariables are defined from the outset, and
      whether or not the results for the primary endpoint are significant.

PMID- 11296632
TI  - [Cystine lithiasis: physiopathology and medical treatment].

PMID- 11296633
TI  - [Accuracy of pressure measurements obtained with a new rectal balloon catheter].
AB  - The accuracy of measurements performed by a balloon catheter used to record
      abdominal pressure during urodynamic investigations was verified on a test bench.
      OBJECTIVE: To study the accuracy and precision of the pressure measurements
      obtained with a new rectal balloon catheter (ref. 95018 Laboratoires Vermed),
      designed to record abdominal pressure during urodynamic assessments. The clinical
      value of this catheter, using air for pressure transmission, is its simplicity,
      as there is no contamination of the perfusion circuit or transducer, no purging
      of the circuit, and artefacts related to movements of the tubing are eliminated.
      METHOD: The catheter was placed in a pressure chamber fitted with a precise,
      calibrated regulation system allowing programmed pressure variations from 10 to
      150 cmH2O. Pressures recorded by the test catheter were compared to reference
      pressures applied to the chamber. The frequency of acquisition of pressure
      measurements was 100 Hertz and the resolution was 10 Hertz. This model was used
      to study the accuracy of pressure measurements and the response times of the
      catheter. Measurements were performed with a volume of 2 ml of air introduced
      into the catheter (volume recommended by the manufacturer), and the optimal
      volume was investigated by inflating the catheter until the best result was
      obtained. The evaluation was based on calculation of the mean difference observed
      between the two measurements and the scatter of the differences observed.
      RESULTS: When the catheter was filled with 2 ml of air, pressures measured by the
      catheter were overestimated an average of 1.1 cmH2O (standard deviation = 1), and
      95% of the differences between the two measurements were within +/- 2.15 cmH2O.
      The optimal air volume was found to be 1.5 ml. With this air volume, no
      significant difference was observed between the two measurements. The mean
      observed difference was 0.2 cmH2O (SD = 1.2), which means that 95% of the
      differences were situated within the range of +/- 2.35 cmH2O. CONCLUSION: The
      pressure recording method with this new catheter is validated in terms of
      physical parameters.

PMID- 11296634
TI  - [Simultaneous chemotherapy/radiotherapy in locally advanced unresectable cancer
      of the bladder].
AB  - The development of new treatment techniques, including concomitant
      chemotherapy/radiotherapy, appears to achieve higher response rates in advanced
      bladder cancer. Previous studies have suggested that continuous infusion
      chemotherapy and concomitant irradiation act synergistically to induce
      significantly increased tumour cell destruction. With the combination of 5FU and
      radiotherapy, the local control rate of transitional cell bladder cancers was 70%
      with a 5-year survival rate of 36% to 62%. Concomitant cisplatin and irradiation
      improved the control of locally advanced bladder cancers, but failed to improve
      overall survival. The use of concomitant cisplatin has no effect on distant
      metastases. These treatment modalities require further evaluation because of the
      relationships between radiotherapy- and drug-induced apoptosis, delayed cell
      death, survival of clonogenic cells, clinical response and overall survival. The
      optimum concomitant chemotherapy/radiotherapy protocol has not yet been defined.

PMID- 11296635
TI  - [Trans-ureteral pyelostomy: 5 cases].
AB  - The authors report 5 cases of extensive loss of substance of the distal ureter
      due to radiation fibrosis, operative trauma or tumour invasion; these lesions
      occurred during the course of a genital tumour in 4 cases and rectal prolapse in
      one case. The lesion was bilateral and radiation-induced in 2 cases and
      unilateral in 3 cases. The patients presented with renal colic in 2 cases, renal
      failure in 1 case and infection in 2 cases (pyelonephritis, septic shock). All
      patients presented with secondary hydronephrosis. The extent of the lesions made
      vesical anastomosis impossible, especially as the bladder was irradiated and/or
      absent in 3 cases. Anastomosis of the proximal ureteric stump onto the
      contralateral ureter was impossible in the presence of bilateral lesions
      requiring diversion of the contralateral ureter or due to the short donor ureter,
      or because of the discordant diameter of the two ureters. Transureteropyelostomy
      was therefore performed in these 5 cases. The postoperative course was uneventful
      4 cases, with a transient anastomotic fistula in only one case. Four of the 5
      patients achieved long-term survival with an excellent clinical and radiological
      result.

PMID- 11296636
TI  - [Contribution of surgical techniques used in liver transplantation in the
      treatment of retroperitoneal tumors].
AB  - The authors describe the surgical technique used in liver transplantation and its
      application to treat retroperitoneal tumours. This technique comprises primary
      mobilization of the liver with easy vascular control. This technique, used in 29
      patients, is simple, facilitates exposure of great vessels which can be
      controlled and allows excellent exposure in difficult cases. Analysis of the
      postoperative course emphasized the absence of hepatic and renal complications,
      as reflected by normal renal function and liver enzymes. The use of this
      technique for renal and adrenal surgery avoids the need for extracorporeal
      circulation and a thoracophrenoabdominal approach, thereby limiting the specific
      complications related to these two procedures.

PMID- 11296637
TI  - [Claude-Nicolas Le Cat (1700-1768), a famous surgeon and urologist of the 18th
      century].
AB  - Le Cat was a famous surgeon in France in the 18th Century, at a time when surgery
      was recognised as a separate specialty and the search for clinicopathological
      correlations was being developed. Le Cat was born in Picardy and studied anatomy
      and surgery in Paris. He was appointed surgeon to the Archbishop of Rouen in
      1726, then head surgeon at Hotel-Dieu hospital in Rouen. He performed two major
      operations: lithotomy for bladder stones and cataract surgery. He developed an
      instrument for lithotomy, the Gorgeret cystotome. His reputation in France and
      Europe is reflected by his numerous academy prizes, publications, and surgical
      notoriety.

PMID- 11296638
TI  - [Inauguration speech for the 94th French Congress on Urology].

PMID- 11296640
TI  - [The 20th century... or the time of conceptual revolutions].

PMID- 11296639
TI  - [Treatment of pheochromocytomas with retroperitoneal laparoscopy].
AB  - OBJECTIVES: Although laparoscopic adrenalectomy has become one of the techniques
      of choice for the treatment of adrenal tumours, this technique has not been
      widely used to treat phaeochromocytoma due to the risks of hypertension before
      control of the adrenal vein. The authors report their experience of
      retroperitoneal laparoscopic adrenalectomy for phaeochromocytoma. MATERIAL AND
      METHODS: From January 1995 to December 1999, 10 (5 right, 5 left) retroperitoneal
      laparoscopic adrenalectomies were performed for symptomatic phaeochromocytoma, in
      4 men and 6 women, aged 40 to 67 years (mean: 51 years). In every case, the
      phaeochromocytoma had been diagnosed by elevated urinary catecholamines,
      abdominopelvic CT scan and positive MIBG scintigraphy. RESULTS: There were no
      conversions to open surgery. The mean operating time was 116 minutes (range: 100
      to 140 minutes). Mean blood loss was 180 ml (range: 0 to 550 ml) and none of the
      patients were transfused. In one case, an injury to the adrenal vein was repaired
      intraoperatively. The mean length of hospital stay was 3.4 days (range: 1 to 12
      days). The mean diameter of the lesion was 38 mm (range: 15 to 110 mm).
      Postoperative complications occurred in two cases (one haematoma and one
      incisional hernia repaired one year later). With a mean follow-up of 21.6 months
      (range: 6 to 46 months), all patients had normal urinary catecholamine levels and
      9 had a normal blood pressure with no antihypertensive therapy. CONCLUSION:
      Retroperitoneal laparoscopic adrenalectomy can be performed for small
      phaeochromocytomas (less than 5 cm). Retroperitoneal laparoscopy is a direct
      approach which allows the surgeon to control the adrenal vein first in order to
      avoid hypertensive crises.

PMID- 11296641
TI  - [Doppler ultrasonography in the function assessment of double J ureteral
      endoprosthesis in patients with extrinsic ureteral obstruction].
AB  - OBJECTIVES: The efficacy of internal urinary drainage by double J stent is
      relatively difficult to evaluate by classical methods. This prospective study
      evaluated variations of the resistance index (RI) in patients with unilateral
      extrinsic ureteric obstruction, requiring internal drainage by double J stent.
      MATERIAL AND METHODS: Variations of the resistance index (RI) and the
      correlations between RI and the results of other investigations were determined
      in a group of 48 patients with unilateral extrinsic ureteric obstruction, treated
      by ureteric stent. The presence of urine from the stented ureteric meatus was
      also assessed. RESULTS: The preoperative assessment demonstrated a sensitivity of
      73% for RI (> 0.7) and 84.5% for DRI for the demonstration of obstruction.
      Following stenting, RI decreased by 11%, with a mean index of 0.66; the RI was
      less than 0.07 in 62.5% of cases. The mean index was 0.68 one month later and
      0.71 three months later (an increase of 0.05 compared to the post-stent
      evaluation). CONCLUSIONS: The resistance index may represent a useful element in
      the assessment of the efficacy of internal drainage by double J stent, while the
      presence of urine in the ureteric orifice may not be helpful.

PMID- 11296642
TI  - [The new uretero-ileal anastomosis technique in Hautmann ileal neobladder].
AB  - OBJECTIVE: Hautmann neobladder is one of the most widely bladder replacement
      techniques in the two sexes. The uretero-ileal stenosis rate is estimated to be
      11% with the initial CAMEY-LE DUC technique. A new anastomosis technique is
      presented in order to improve this postoperative complication. MATERIALS AND
      METHODS: Two 5 to 10 cm ileal segments are prepared at the two extremities of the
      W of the neobladder to receive the largely spatulated ureters. The anastomosis is
      performed directly on the ileal resection margin, in a strictly retroperitoneal
      position. Between December 1996 and December 1998, the technique was performed in
      89 patients including 19 women. One hundred and sixty six renal units (RU) were
      analysed by preoperative renal ultrasound, repeated after 1, 3 and 6 months and
      then every 6 months. Urine culture was performed monthly for 6 months. RESULTS:
      Thirteen RU were dilated (grade II and III) preoperatively (7.8%). No secondary
      anastomotic stenosis was observed with a mean follow-up of 5.8 +/- 7.6 months. Of
      the 166 RU examined, 129 were normal, 13 preoperative dilatations were improved
      and 24 RU presented minimal postoperative dilatation (grade I). Ileo-ureteric
      reflux was observed on the postoperative retrograde cystography in two cases. The
      only complication was acute pyelonephritis (1.1%) at 1 month. 90% of urine
      cultures were sterile after 6 months. CONCLUSION: Modification of uretero-ileal
      anastomosis by the "double chimney" technique is performed without tension by
      placing the two ureters in an anatomical position without plication or torsion.
      Preservation of the ureteric blood supply contributes to the low complication
      rate and a decreased risk of stenosis. However, the technique needs to be
      validated by analysis of the results with a longer follow-up.

PMID- 11296643
TI  - [Long-term results of interferential current stimulation in the treatment of
      bladder instability].
AB  - OBJECTIVE: To study the late results of interferential current stimulation in the
      treatment of detrusor instability. MATERIAL AND METHODS: 62 patients with
      detrusor instability refractory to medical treatment by anticholinergic drugs
      were treated by interferential current stimulation. This technique combines the
      advantages of retraining stimulation with external application. This
      retrospective study was based on 62 patients (43 children, 11 men and 8 women)
      presenting with detrusor instability between January 1990 and December 1997. All
      patients were assessed clinically and by a radiological, bacteriological and
      urodynamic work-up prior to treatment. The mean follow-up was 5 years (range: 18
      months to 10 years). RESULTS: The results of this technique were excellent, with
      80.9% of cures at one year, but they tended to fade over time to 40% of cures at
      5 years. However, results which deteriorate after one year can generally be
      maintained by performing 5 maintenance sessions every 12 or 18 months.
      CONCLUSION: Treatment of detrusor instability by interferential current is a
      reliable technique which constitutes an alternative to the other methods of
      retraining stimulation and can be performed in cases of instability refractory to
      anticholinergic drugs, before considering neuromodulation or surgery. Five to 10
      maintenance sessions every 12 or 18 months ensure stable long-term results in the
      majority of cases.

PMID- 11296644
TI  - [Prospective study comparing ultrasonography guided trans-rectal biopsy and
      finger guided trans-perineal biopsy in the diagnosis of prostatic cancer].
AB  - OBJECTIVE: To compare ambulatory ultrasound-guided transrectal biopsy and finger
      guided transperineal biopsy. MATERIAL AND METHODS: From June 1997 to October
      1999, 51 patients were simultaneously biopsied by the two techniques and by the
      same operator, 30 min after antibiotic prophylaxis with 200 mg of Ciprofloxacin
      by intravenous injection. Transperineal biopsies were performed first, followed
      by ultrasound-guided transrectal biopsies. Six cores were obtained with each
      technique, from the apex, the middle and the base of each lobe. RESULTS: For a
      PSA level between 4 and 10 ng/ml, 6 cancers were detected in 23 patients (26%)
      and one cancer was only detected via the transrectal route. For a PSA level
      greater than 10 ng/ml, 17 cancers were detected in 28 patients (60%), 15 (53%) by
      transperineal biopsy and 11 (39%) by transrectal biopsy. Six cancers were only
      detected by transperineal biopsy and two were only detected by transrectal
      biopsy. No statistically significant difference was observed between the numbers
      of positive biopsies obtained with the two techniques. CONCLUSION: The use of
      ultrasonography is not essential to perform systematic biopsies. Rather than the
      technique used, the detection of prostate cancer is improved by performing 12
      cores instead of 6.

PMID- 11296645
TI  - [Correlation between Gleason score of prostatic biopsies and the one of the
      radical prostatectomy specimen].
AB  - The Gleason score obtained on prostatic biopsies is an essential element in the
      treatment decision for localized prostate cancer. The objective of this study was
      to evaluate the correlation between the biopsy Gleason score and the definitive
      Gleason score and to propose a classification into 3 groups in order to improve
      this correlation. MATERIAL AND METHODS: One hundred radical prostatectomies were
      performed between 1995 and 1998. Eighty four of these patients underwent 6
      biopsies. The Gleason score of the biopsies and operative specimens were
      compared. The concordance between the biopsy Gleason score and the operative
      specimen Gleason score was initially analysed score by score. The concordance was
      then established according to three groups, well differentiated tumours (score 2
      4), moderately differentiated tumours (score 5-7), poorly differentiated tumours
      (score 8-10). RESULTS: The concordance between the biopsy Gleason score and the
      operative specimen Gleason score was perfect in only 37% of cases. A 1-point
      difference of the score was observed in 35.7% of cases and a 2-point or greater
      difference was observed in 27.3% of cases. By classifying patients into 3 groups,
      the concordance increased from 37% to 72.6%. CONCLUSION: The classification of
      patients into three distinct groups (well, moderately and poorly differentiated
      tumours) increases the concordance between the biopsy Gleason score and the
      definitive Gleason score. However, the limitations of the biopsy Gleason score
      must be kept in mind, particularly in the case of low-grade tumours.

PMID- 11296646
TI  - [Variations of the practice of radical prostatectomy in France].
AB  - OBJECTIVE: A description of radical prostatectomy (PR) practice in the general
      population in France has never been reported. The objective of this study was to
      analyse RP practice in France, and its determinants and geographical variations
      based on the CCAFU-Francim survey on prostate cancer (PC) diagnosed in 1995.
      MATERIAL AND METHOD: 175 PR were performed on the sample of 798 patients selected
      at random from the cases of PC identified in 1995 by four cancer registries (Bas
      Rhin, Calvados, Isere and Tarn). Analysis was based on tumour characteristics,
      diagnostic methods and histopathological results. Multivariate analysis by
      logistic regression taking into account age, PSA and clinical stage studied
      variations between departments and types of urology practice (private or public).
      RESULTS: The mean age of the patients at the time of the diagnosis was 65.3 years
      (46-76). The median PSA was 18.3 ng/ml (1-184). The diagnosis was made by
      biopsies (91%) which were systematized in 74% of cases or by transurethral
      resection (7%). The clinical stage was T1 (22.3%), T2 (64%), T3 (8.6%), N+
      (0.611) and unknown (4.5%). The pathological stage was pT2N0 (46.3%), pT3N0
      (40%), pT4N0 (1.7%), pTxN0 (8.6%) and unknown (3.4%). Adjuvant treatment
      (radiotherapy: 13.7%, endocrine therapy: 13.7% or both: 31%) was performed in 54
      patients (31%). Multivariate analysis showed that the adjusted probability to be
      treated by RP was 3 times higher in one department compared to others and 2.6
      times higher in the private sector. CONCLUSION: This study of RP practice in the
      general population shows a concordance with the 1995 recommendations, but it also
      shows practice variations according to the region and the type of practice,
      reflecting different schools of thought and medical education within the same
      country.

PMID- 11296647
TI  - [Comparative results of the treatment of post-traumatic ruptures of the
      membranous urethra with endoscopic realignment and surgery].
AB  - OBJECTIVE: Retrospective, comparative study of the long-term results of
      endoscopic realignment and surgery in the treatment of complete rupture of the
      posterior urethra. MATERIAL AND METHODS: Between 1989 and 1998, 40 men were
      managed for traumatic posterior rupture of the membranous urethra: 30 were
      treated by endoscopic realignment for complete rupture while 10 were treated by
      surgery (perineal or transsymphyseal incision) for a long stenosis (> 3 cm)
      secondary to extensive rupture of the urethra. RESULTS: With a mean follow-up of
      30 months (12 to 72 months), all patients treated by endoscopic realignment are
      continent and urinate with a satisfactory urine output (Qmax > or = 15 ml/s).
      This result was obtained after internal urethrotomy in 7 patients (23.33%) and
      transperineal urethroplasty in one patient. Six patients developed persistent
      impotence (20%). For the ten patients treated surgically, the voiding stream was
      considered to be satisfactory (Qmax > 15 ml/s in 6 patients while 4 developed
      short strictures accessible to endoscopic urethrotomy. Nine patients are
      continent, while one completely incontinent patient with perineal fistulas
      required a continent cystostomy. Four out of 10 patients reported sexual
      impotence. CONCLUSION: Endoscopic realignment of complete rupture of the
      membranous urethra is a simple, minimally aggressive technique, ensuring optimal
      preservation of continence and sexuality in young subjects.

PMID- 11296649
TI  - [Consumption coagulopathy disclosing prostatic cancer].
AB  - Prostate cancer can be complicated by disseminated intravascular coagulation. The
      severity of this complication justifies rapid medical treatment. The authors
      describe the case of a man in his seventies presenting with disseminated purpuric
      lesions due to disseminated intravascular coagulation. Prostate cancer was
      documented concomitantly. The clinical course was rapidly unfavourable despite
      endocrine therapy and blood transfusions. The mechanism of disseminated
      intravascular coagulation in prostate cancer has not been clearly elucidated, but
      appears to be related to release of procoagulant substances during certain
      diagnostic or therapeutic procedures. The severity of the prognosis justifies
      rapid introduction of endocrine therapy, which is not immediately effective. It
      can help to achieve a period of remission if the haemorrhagic syndrome is
      controlled. Further studies may help to improve therapeutic management.

PMID- 11296648
TI  - [Urogenital tuberculosis. Experience in 10 years].
AB  - OBJECTIVE: To review the clinical, imaging and therapeutic aspects of urogenital
      tuberculosis. MATERIAL AND METHODS: From April 1989 to April 1999, 57 patients
      with urogenital tuberculosis were reviewed in our department. This series
      consisted of 32 males and 25 females with a mean age of 40 years (range: 18 to 72
      years). RESULTS: The most frequent clinical symptoms were irritative symptoms
      (47.3%). Fever, anorexia and weight loss were rare (11%). 16% of patients had an
      isolated genital lesion. 14% presented with renal failure (mean serum creatinine:
      18 mg/l). Only 3 cases (5.2%) presented with bacilluria. Urography showed
      abnormalities in 80% of cases. The most frequent abnormality was a non
      functioning silent kidney in 23 cases (40.3%). The positive diagnosis was based
      on bacteriological (5 cases) and histological data (52 cases). Treatment
      consisted of antituberculous chemotherapy in all patients, in combination with
      surgery (75%), and/or endourological procedures (26.3%). Nephrectomy is still
      indicated for non-functioning tuberculous kidneys in order to prevent the
      development of hypertension, abscess and fistulas. CONCLUSION: The diagnosis of
      urogenital tuberculosis is difficult and often late. A surgical or endourological
      procedure is often necessary to preserve renal function and to improve quality of
      life.

PMID- 11296650
TI  - [Acute urinary retention secondary to clear cell adenocarcinoma of the urethra].
AB  - The authors report a case of primary clear cell cancer of the urethra in a woman
      presenting with acute urinary retention. The diagnosis was based on cystoscopy
      and confirmed by histological examination of urethral biopsies. Treatment
      consisted of urethrocystectomy with creation of an "Indiana pouch". The
      pathological stage was T3N2M0 [1]. Three months postoperatively, the patient
      presented with inguinal lymph node metastases. She was treated with 3 courses of
      chemotherapy (mitomycin and 5-fluorouracil) combined with radiotherapy. With a
      follow-up of 10 months, the patient is still alive and inguinal lymph nodes have
      regressed. This case report emphasizes the rarity of this histological type and
      describes the management of urinary retention in a woman when an underlying
      specific disease is suspected.

PMID- 11296651
TI  - [Dedifferentiation of mature teratomas secondary to testicular cancer: report of
      2 cases].
AB  - The authors report two cases of adenocarcinomatous dedifferentiation of a
      recurrent mature teratoma arising 3 and 20 years after the initial resection.
      This is a rare event, occurring after macroscopically or microscopically
      incomplete resection of a mature teratoma. The nature of this recurrence was
      difficult to determine prior to histological examination. However, PET scan
      suggests the diagnosis of malignant teratoma in the presence of increased uptake
      by the lesion. These tumours have a poor prognosis. Treatment consists of
      complete resection of the tumour mass. The possibility of long-term malignant
      dedifferentiation of a teratoma therefore requires prolonged and regular life
      long surveillance of patients presenting a mature teratoma after chemotherapy for
      non-seminomatous germ cell tumour of the testis.

PMID- 11296652
TI  - [Youssef's syndrome].
AB  - Youssef's syndrome is an uncommon form of vesico-uterine fistula, caracterized
      clinically by the association: amenorrhea cyclic, hematuria without urinary
      leakage. This entity is the result of pressure gradient between uterin cavity and
      bladder reservoir. We report on one case.

PMID- 11296653
TI  - [Retroperitoneal laparoscopic surgery and carcinogenic risk].
AB  - OBJECTIVE: To retrospectively evaluate the development of metastasis at trocar
      sites, local recurrence and distance metastases associated with retroperitoneal
      laparoscopic surgery performed in the context of a malignant tumour. METHODS:
      From 1994 to 1999, 228 retroperitoneal laparoscopic surgical operations were
      performed in our centre. Fifty six operations (24.6%) were performed for
      malignant tumours and comprised 41 radical nephrectomies and 8 partial
      nephrectomies for renal tumour and 7 nephro-ureterectomies for upper urinary
      tract tumours. The pathological stage and surgical margins were correlated with
      TNM 1997 stage. Postoperative data were obtained by physical and radiological
      examination performed one month and three months after the operation and then
      every six months. Metastases at the trocar site, local recurrences and distant
      metastases were investigated. The specific progression-free survival was
      calculated according to the Kaplan-Meier method. RESULTS: The mean follow-up was
      24.9 +/- 13.85 months. All patients had tumour-free surgical margins. No trocar
      site metastasis was observed. For retroperitoneal laparoscopic radical
      nephrectomies: one patient developed a local recurrence with liver metastases 9
      months after the operation (pT3G2) and died 19.7 months after the operation. One
      patient with a pT3G3M+ renal tumour at the time of diagnosis died 23.1 months
      after radical nephrectomy with no signs of local recurrence. For laparoscopic
      retroperitoneal nephro-ureterectomies: one patient with a pT3G3 lesion developed
      a local recurrence at 12.1 months and died 26.6 months after surgery. One patient
      with a pT1G2 tumour developed bone metastases at 9 months and died 29 months
      after the operation. The recurrence-free survival at 54 months was 91% for
      radical nephrectomies, 71% at 30 months for nephro-ureterectomies and 100% at 49
      months for partial nephrectomies. CONCLUSION: Malignant tumours of the upper
      urinary tract can be managed by retroperitoneal laparoscopy. The short-term
      results suggest that this surgical technique is not associated with an increased
      risk of trocar site metastases or local recurrence and that recurrence-free
      survival rates comparable to those reported in series of conventional surgery.

PMID- 11296654
TI  - [Unusual testicular tumor: Leydig, Sertoli, and granulosa cell mixed tumor].
AB  - We report an unusual case of a mixed granulosa-Sertoli-Leydig cell testicular
      tumor in a 16 year old man, who presented with bilateral gynaecomastia. A few
      cases have been published in the literature. Based on a case report, the authors
      describe the clinical, histopathological and therapeutical features of this rare
      affection.

PMID- 11296655
TI  - [Prostatic leiomyosarcoma (report of 2 cases)].
AB  - The authors report 2 cases of prostatic leiomyosarcoma. The first patient was not
      operated because of a severely debilitated state and died a fortnight after
      admission to hospital. The second patient underwent cystoprostatectomy with ilio
      obturator lymph node dissection. Resection margins and lymph node dissection were
      negative and no further treatment was required. With a 10-year follow-up, the
      clinical and radiological assessment was normal. The diagnostic and therapeutic
      aspects of this rare prostatic tumour are discusses.

PMID- 11296656
TI  - [Management of oncocytoma in transplanted kidney].
AB  - The authors report a case of oncocytoma arising in a transplanted kidney. The
      diagnostic and therapeutic management is discussed and compared to the limited
      data reported in the literature on this subject. Immunosuppression of renal
      transplant recipients does not appear to increase the incidence of graft tumours,
      but, in the authors' opinion, modifies the conservative attitude generally
      proposed for this type of tumour.

PMID- 11296657
TI  - [Spontaneous thrombosis of left varicocele].
AB  - Spontaneous thrombosis of a varicocele is a rare event and difficult to diagnose,
      as the clinical symptoms during the acute phase can simulate torsion of the
      spermatic cord or strangulated inguinal hernia leading to a useless surgical
      exploration. The authors report a case of spontaneous thrombosis of a varicocele
      which was diagnosed clinically, allowing conservative medical treatment.

PMID- 11296658
TI  - [Urethral diverticulosis in women. Analysis of 15 cases].
AB  - OBJECTIVE: To evaluate the aetiopathogenic, diagnostic and therapeutic aspects of
      urethral diverticula in women. MATERIAL AND METHODS: Over a 10-year period
      (January 1990 to December 1999), 15 patients with a mean age of 36 years (range:
      25 to 46 years) with urethral diverticulum were included in this study. The mean
      parity was 2 with a history of long and difficult delivery in 6 cases. All
      patients presented lower urinary tract symptoms with a clinical diverticulum on
      gynaecological examination (14 cases) or on retrograde and voiding
      cystourethrography (14 cases) or intravenous urography (one case).
      Diverticulectomy was performed via a transvaginal approach in the dorsal
      position. RESULTS: There were no postoperative complications. All patients were
      reviewed with a mean follow-up of 3 years. The urinary symptoms had completely
      disappeared in 14 cases. One patient was reoperated for recurrent diverticulum.
      CONCLUSION: Young women with recurrent voiding disorders must be examined for the
      presence of urethral diverticulum that can be confirmed by cystourethrography.
      Transvaginal diverticulectomy in the lithotomy position is the operation which
      ensures the best results.

PMID- 11296659
TI  - Our recent studies on sensory transduction: from vision to taste.
AB  - The transduction in photoreceptors and chemoreceptors has common mechanisms. In
      photoreceptors, activation of rhodopsin by light triggers the enzymatic cascade
      mediated by a G-protein, transducin. In olfactory cells activation of the
      receptor molecule by odorant triggers the enzymatic cascade mediated by a G
      protein, Golf. In taste receptor cells biochemical studies have also suggested a
      metabotropic transduction hypothesis, but we recently identified a cationic
      channel that was directly gated by a bitter taste substance. By reviewing these
      recent studies carried out in our laboratory in the last 10 years, the
      transduction machinery in these sensory receptor cells are summarized.

PMID- 11296660
TI  - Molecular mechanisms of anesthesia.
AB  - Anesthesia was a blessing to humankind. It is a miracle that simple molecules
      such as chloroform (CHCl3), diethyl ether (CH3.CH2.O.CH2.CH3), or nitrous oxide
      (N2O) induce a state of unconsciousness where patients can tolerate surgery. The
      diversity of the structures of these molecules indicates that there are no common
      receptors. The action of anesthetics is nonspecific and physical. After the
      demonstration by Meyer and Overton that anesthetic potencies correlate to their
      solubility into olive oil, the nonspecific lipid theories monopolized anesthesia
      theories for almost a century. The dominance of lipid theories invited repulsions
      against the nonspecificity idea. Protein theories that stress receptor bindings
      became the top mode. Nevertheless, the wide varieties of anesthetic molecules and
      the wide varieties of responding systems are difficult to reconcile with the
      specific interaction concept. This article discusses the recent progress and
      controversies on the molecular mechanisms of anesthesia. Anesthetics are unique
      drugs in pharmacology. They affect all macromolecules. The only comparable drugs
      are disinfectants. Both are nonspecific drugs. We use alcohols and phenols to
      wipe off the injection sites. We do not use penicillin or any other antibiotics
      for this purpose, because they are specific binders. Interestingly, these two
      nonspecific drugs opened the window for the modern medicine.

PMID- 11296661
TI  - The development and applications of the bacterial artificial chromosome cloning
      system.
AB  - The development of the Bacterial Artificial Chromosome (BAC) system was driven in
      part by the Human Genome Project as a means to construct genomic DNA libraries
      and physical maps for genomic sequencing. The BAC system is based on the well
      characterized Escherichia coli F-factor, a low copy plasmid that exists in a
      supercoiled circular form in host cells. The structural features of the F-factor
      allow stable maintenance of individual human DNA clones as well as easy
      manipulation of the cloned DNA. BACs are currently used in a wide array of
      applications from genome sequencing to gene discovery. This paper describes the
      key elements in the development of the BAC system and its current notable
      applications.

PMID- 11296662
TI  - Arterial anatomy of subdermal plexus of the face.
AB  - The subdermal plexus of the face was angiographically investigated using ten
      fresh cadavers injected with a radio-opaque lead oxide-gelatin mixture over the
      entire body. The subdermal vessels were unique in each region of the face, and
      the author classified the vessels into three kinds according to their running
      forms, shape of their skin territories, and arrangement of the territories. A
      kind of line by anastomoses of the subdermal vessels which are mutually adjacent
      or by the quite elongated subdermal vessels was observed. The line depicted by
      those vessels almost coincided with the relaxed skin tension lines. The author
      believes that when local flaps in the face are utilized, the flaps should be
      better designed along the line to obtain better blood supply and aesthetic
      outcome.

PMID- 11296663
TI  - Whats new in genodermatoses?
AB  - Recent genetic analysis of the genodermatoses, in particular the palmoplantar
      keratodermas, has identified the important role of proteins involved in the
      regulation and formation of epidermal cell junctions. There are four major types
      of junction, of which three have been demonstrated to be important in skin, and
      in which component proteins such as desmoplakin and connexins are mutated in
      epidermal disease. These are the gap junctions, desmosomes and adherens
      junctions. These junctions are responsible for cell-cell adhesion and
      communication, key properties to maintain the normal cellular phenotype and
      tissue architecture.

PMID- 11296664
TI  - Characterization of CD1d in mucosal immune function: an immunotherapeutic target
      for inflammatory bowel disease.
AB  - In addition to the classical MHC class I and class II molecules, human intestinal
      epithelial cells also express nonclassical MHC class I-like molecules on their
      cell surface. CD1d is a non-polymorphic MHC-like molecule whose expression is
      mainly localized to the epithelial cells of the gastrointestinal tract. The
      biochemical structure of CD1d on intestinal epithelial cells (IECs) exists in two
      forms: a 37-kD nonglycosylated, beta 2-microglobulin (beta 2M) independent and a
      48-kD glycosylated, beta 2M dependent form. Immunolocalization studies suggest
      that the 37-kD nonglycosylated form of CD1d is limited to the apical cell surface
      whereas the 48-50-kD glycosylated, beta 2M dependent form of CD1d is expressed
      both on the apical and the basolateral surfaces. The beta 2M association with
      CD1d seems to be important in regulating the pattern of glycosylation and the
      localization of CD1d within the cell based upon studies of the structure of CD1d
      in a transfected model cell line and in polarized epithelial cell monolayers. The
      functional role of intestinal CD1d remains unknown. However, based upon in vitro
      studies of the antigens presented by human CD1d and mouse CD1d, CD1d expressed on
      IECs likely presents a very hydrophobic glycolipid molecule possibly from the
      cell wall of bacteria or host cells. The processed-lipid antigen presented by
      CD1d may then involve a yet-to-be-identified subpopulation of the resident,
      oligoclonal alpha beta TCR CD8+ intestinal intraepithelial lymphocyte (iIEL) T
      cells. Subsequently, these T cells would be very important in regulating the
      local immune response by producing cytokines and recruiting other immune
      modulating cells to destroy infected cells, regenerate normal IECs, and possibly
      downregulate activated T cells to maintain mucosal integrity.

PMID- 11296666
TI  - Taiei Miura and Franco-Japanese friendship in psychiatry.
AB  - Japanese medicine enthusiastically adopted many aspects of Western medicine,
      especially German, during and after Japan's modernization. After the war, the
      policy giving priority to German medicine changed greatly, and American medicine
      replaced German medicine in postwar days. Some people, however, question whether
      it is proper to get medical information one-sidedly from a single country. Faced
      with the situation of whether German or American medicine should occupy the
      dominant position in Japan, some doctors chose to establish ties with French
      medicine. Professor Taiei Miura (1901-1995) re-established an intimate
      relationship, broken off during the war, in the medical field between Japan and
      France. Much information was to be learned from French medicine, particularly in
      clinical neurology and psychiatry. In this essay, we relate the details of how
      Miura became interested in French medicine, went to study in France, then
      contributed greatly to Franco-Japanese friendship.

PMID- 11296667
TI  - [Neuromuscular erectile dysfunction: the need for a correct identification and
      application of a targeted treatment].

PMID- 11296668
TI  - [Expression of epidermal growth factor receptor and p53 protein in superficial
      cancer of the urinary bladder].
AB  - OBJECTIVE: To determine the relationship of the immunohistochemical expression of
      p53 and EGF-r (epidermal growth factor receptor) and the recurrence rate and
      disease-free interval in superficial bladder cancer. METHODS: 144 patients with
      superficial transitional cell carcinoma of the bladder were studied over a period
      of three years. Direct dilution anti-EGF-r monoclonal antibody (Biogenex, San
      Ramon, CA 94583, USA) was utilized for EGF-r determination. Anti-p53 mouse
      monoclonal antibody (DO7, Novocastra, Newcastle, 24 Claremont Place, UK) at a
      concentration of 1:100 was utilized for protein p53 determination and was
      considered negative if less than 10% of the tumor cells were stained and positive
      if 10% to 100% of the cells stained. EGF-r was determined only as either positive
      or negative regardless of percent of expression. RESULTS: 55 patients (38%)
      showed EGF-r and 14 (9.7%) showed p53 expression. The disease free survival was
      54.08 months in the patients that showed EGF-r expression vs 30 months for those
      that did not, the difference being statistically significant (p = 0.027).
      However, no differences were found in this regard for p53 expression. Tumors that
      expressed EGF-r recurred in the same site as that of the primary tumor. By
      contrast, those that did not express EGF-r recurred in another or in multiple
      sites. CONCLUSIONS: The risk of recurrence is lower in bladder tumors that
      express EGF-r than those that do not, and when they recur, this generally occurs
      in the same site as the primary tumor. However, determination of p53 expression
      was not useful in determining the risk of recurrence or progression of
      superficial bladder tumors.

PMID- 11296669
TI  - [Fine-needle aspiration cytology in the diagnosis of prostate cancer. Results].
AB  - OBJECTIVE: To demonstrate the utility of fine needle aspiration biopsy in the
      diagnosis of prostatic tumors, basically carcinoma of the prostate.
      METHODS/RESULTS: The clinical records of 497 patients who underwent fine needle
      aspiration biopsy were reviewed. Age, skin color, clinical diagnosis by DRE,
      transrectal core biopsy, correlation between clinical and histological diagnosis,
      distribution according to type of adenocarcinoma, correlation between cytological
      and histological diagnosis, and complications were analyzed. Of the 497 patients,
      162 had histological confirmation. Of these 162 patients, the Galen and Gambino
      statistical method was utilized in 132 which represented the true negatives and
      positives. Sensitivity was 86%, specificity 96%, positive predictive value 91%,
      negative predictive value 93%, and efficiency was 92%. The complication rate was
      low. CONCLUSIONS: Fine needle aspiration biopsy is a safe and efficient
      diagnostic method in prostatic tumors and causes minimal discomfort to the
      patient.

PMID- 11296670
TI  - [Prognostic value of inverted papilloma of the lower urinary tract].
AB  - OBJECTIVE: Inverted papilloma of the urothelium accounts for 2.2% of urothelial
      neoplasms. Its oncologic significance is unclear; its potential for recurrence
      and/or progression is not well-known. Our experience from 1976 to 1999 is
      reviewed. METHODS: From 1976 to 1999, 31 patients with urothelial inverted
      papilloma of the lower urinary tract have been treated in our service: 17
      presented previous and/or synchronous association with urothelial carcinoma
      (group I) and 14 had primary inverted papilloma (group II). The recurrence and
      progression rates for each group were determined and compared. The overall
      recurrence and progression rates were also determined. Two patients (one from
      each group) were lost to follow-up. The remaining 29 patients had a mean follow
      up of 51.3 months (range 3-125). RESULTS: 12 patients (41.4%) showed recurrence
      in the form of bladder carcinoma; 10 from group I (10/16; 62.3%) and 2 from group
      II (2/13; 15.4%) (p < 0.05). Mean time to recurrence was 17.9 months (range 3
      58). Disease free interval was higher in group II (p < 0.05). Progression to
      infiltrating tumor was observed in three patients; all three had associated
      superficial bladder carcinoma (group I). The mean time to progression was 30.7
      months (range 18-38). No statistically significant differences were found in the
      percentage of progression between both groups. CONCLUSIONS: Inverted papilloma of
      the lower urinary tract showed a high incidence of association with urothelial
      carcinoma and a high recurrence rate, even in primary tumors. Therefore it should
      be considered a tumor of low grade malignancy that should be followed regularly.

PMID- 11296671
TI  - [Treatment of urolithiasis in children and adolescents with extracorporeal
      lithotripsy and adjuvant urologic procedures].
AB  - OBJECTIVE: To determine the efficacy of ESWL treatment in children and the need
      for auxiliary urological procedures. In a retrospective analysis we investigated
      the number of auxiliary procedures and the stone-free rate in children after ESWL
      treatment. METHODS: 28 girls and 21 boys with a total of 56 stones were treated
      from January 1990 to January 1999. ESWL was carried out on either the Lithostar
      Plus or the Modulith SL20/SLX. Auxiliary procedures were subdivided into curative
      (ureterorenoscopy, percutaneous nephrolitholapaxy) and adjuvant (urethral stent,
      nephrostomy). RESULTS: 34.7% of the children were stone-free after the first ESWL
      treatment; 40.8% of the children were discharged with residual stone particles
      ready for spontaneous passage; 24.5% underwent re-ESWL treatment. Auxiliary
      urological procedures were required in 28.6% of the cases (adjuvant 18.3%,
      curative 10.3%). CONCLUSIONS: Extracorporeal shock wave lithotripsy is also a
      highly effective method of treatment for urolithiasis in children. However,
      curative or adjuvant auxiliary urological measures are required. In order to
      achieve high success rates, it is advisable to perform this method of treatment
      in centers with broad experience in ESWL and endourological procedures in
      children.

PMID- 11296672
TI  - [Sexual activity and surgery of benign prostatic hyperplasia].
AB  - OBJECTIVE: To analyze the sexual activity of patients before and after surgery
      for BPH and to determine the factors influencing sexual activity after
      prostatectomy. METHODS: The sexual activity of 189 patients were evaluated before
      and 6 months after surgery for BPH. Sociodemographic variables, severity of
      prostatic symptoms (IPSS), quality of life (SF-36) and surgery-related data were
      also analyzed. RESULTS: Before surgery, 59% of the patients had sexual activity;
      70.9% of patients < 70 years old and 41.6% of those > 70. Of the patients with
      associated chronic pathologies, 45.5% had no sexual activity and complained of
      vascular and CNS problems (50% in both cases). A higher proportion of patients
      with IPSS > or = 20 showed changes in sexual activity (42.3%). The SF-36 quality
      of life scores for General Health (p = 0.0018), Physical Performance (p < 0.01)
      and Vitality (p = 0.007) were higher in patients who preserved sexual activity.
      After surgery, 5.6% of previously active patients reported no sexual activity and
      66.2% of those who had no sexual activity prior to surgery recovered sexual
      potency. Maintenance or recovery of sexual activity after surgery was associated
      with a better quality of life prior to surgery, basically in the SF-36 Health
      Survey for Vitality (p < 0.0001), Social Function (p = 0.006), General Health (p
      = 0.009) and Mental Summary Index (p = 0.005), an improvement in the IPSS score
      (p = 0.02) and the absence of postoperative complications (p = 0.016).
      CONCLUSION: Sexual activity in patients with BPH is higher in the younger
      patients with no associated pathologies, milder prostatic symptoms and better
      quality of life. A high percentage of patients with no sexual activity prior to
      surgery reported recovery of sexual potency after surgery. Sexual activity after
      surgery is associated with a better quality of life before surgery, basically in
      the mental aspects, improvement of prostate symptoms and the absence of
      postoperative complications.

PMID- 11296673
TI  - [Retroiliac ectopic ureter opening to the seminal vesicle].
AB  - OBJECTIVE: To describe a case of right retroiliac ectopic ureter opening into the
      seminal vesicle, an uncommon congenital malformation. METHODS/RESULTS: This
      anomaly was diagnosed in a 24-year-old male with recurrent acute right
      epididymitis based on the clinical, ultrasound and CT findings. Cystoscopy and
      IVP provided no additional information. Surgical exploration showed right renal
      agenesis and a retroiliac ectopic ureter opening into a dilated right seminal
      vesicle. These structures were resected. Patient evolution was satisfactory with
      no recurrence of the infective episodes. CONCLUSIONS: Diagnosis of this anomaly
      is based on clinical suspicion and the findings of the diagnostic imaging
      techniques. Surgical exploration, which is only required in symptomatic patients,
      will establish the correct diagnosis and treatment.

PMID- 11296674
TI  - [Prostatic syndrome and pleural effusion: are they different diseases?].
AB  - OBJECTIVE: To report an uncommon association of prostate and lung cancer.
      METHODS: The characteristics of both tumors, their association with tumors in
      other sites and the time of presentation are analyzed. RESULTS: Both tumors were
      in the advanced stages. Metastatic carcinoma of the prostate was discarded due to
      the form of presentation. CONCLUSIONS: Although the association of prostate and
      lung cancer is uncommon, the possibility of synchronous tumors should be
      considered in patients with urinary and pulmonary symptoms suggestive of
      neoplasm. It is important to determine if the lesion is a metastasis, since the
      prognosis depends on the second tumor.

PMID- 11296675
TI  - [Spurious renal tumor: acute lobar nephronia].
AB  - OBJECTIVE: To report a case of acute lobar nephronia, an unusual form of
      localized renal infection, and review the literature with special reference to
      the clinical features, ultrasound and CT findings that distinguish this condition
      from other renal masses (abscess, infected cyst and renal carcinoma).
      METHODS/RESULTS: A female patient presented at the emergency services with
      symptoms and signs compatible with pyelonephritis. An admission abdominal
      ultrasound scan demonstrated a solid mass in the left inferior renal pole. CT
      showed a renal mass with peripheral enhancement after infusion of contrast and
      central striation. Blood and urine analyses were compatible with renal infection.
      Acute lobar nephronia was suspected and antibiotic treatment was administered.
      Control ultrasound and CT examinations performed one month after instituting
      antibiotic treatment showed the mass had disappeared. CONCLUSIONS: Acute lobar
      nephronia should be considered in all patients with a renal mass detected during
      an episode of urinary infection. Correlation of the clinical and radiological
      findings, and resolution of the mass with appropriate antibiotic therapy will
      confirm the diagnosis.

PMID- 11296676
TI  - [Genital wound caused by low-speed fire arm].
AB  - OBJECTIVE: To report a case of genital gunshot injuries and review the
      literature. METHODS: A case of low velocity multiple gunshot penile injuries is
      described. Surgical exploration was performed, gunshot removed and the albuginea
      repaired. A broad spectrum antibiotic was administered prophylactically for
      infection. RESULTS: Good cosmetic and functional results, including sexual
      potency and voiding, were achieved. CONCLUSIONS: Surgical exploration is
      mandatory in genital gunshot injuries. The best approach to the albuginea is by a
      crown incision and denudation of the penile skin, which permits surgical repair
      with excellent cosmetic results.

PMID- 11296677
TI  - [Influence of Professor Alexander von Lichtenberg (Berlin) on Spanish urology of
      the 20th century].

PMID- 11296678
TI  - [Bladder megalithiasis].
AB  - OBJECTIVE: To present a case of giant calculus of the bladder. METHODS/RESULTS:
      Herein we describe a case of a giant calculus of the bladder in a 72-year-old
      patient with almost twenty years' evolution without urological control and with
      symptoms of prostatic disease. Surgery disclosed a giant calculus of 12 x 9 cm
      weighing approximately 1 kg adhered to the bladder mucosa. CONCLUSIONS: Although
      the number of cases have dropped in our setting due to the technological
      advancements and availability of health services, giant calculus of the bladder
      is not an insignificant or rarely diagnosed condition.

PMID- 11296679
TI  - [Adrenal gland myelolipoma: radiological view].
AB  - OBJECTIVE: To report a case of adrenal myelolipoma in a female patient with a
      history of arterial hypertension and increased plasma aldosterone levels.
      METHODS: Evaluation by CT and ultrasound, and anatomopathological analysis were
      performed. RESULTS: The CT and ultrasound scans showed a fat-containing adrenal
      mass. The patient underwent surgery. Histological analysis of the surgical
      specimen demonstrated a myelolipoma, a benign tumor composed in varying
      proportions of adipose and hematopoietic tissue. CONCLUSIONS: A diagnosis of
      adrenal myelolipoma must be considered when a fat-containing adrenal mass is
      demonstrated by ultrasound, CT or MRI.

PMID- 11296680
TI  - [Verrucous carcinoma of the penis: report of 2 cases].
AB  - OBJECTIVE: To report two cases of verrucous carcinoma of the penis, a rare tumor
      with a characteristic course and specific treatment that accounts for
      approximately 1% of tumors in the male. METHODS: Two patients, aged 86 and 51
      years, with verrucous carcinoma of the penis are described. Treatment was by
      partial penectomy and resection of the glans penis, respectively. The
      anatomopathological characteristics and prognostic aspects are reviewed.
      RESULTS/CONCLUSIONS: Verrucous carcinoma of the penis usually presents as an
      exophytic lesion in the glans penis or prepuce and should be distinguished from
      epidermoid carcinoma which carries a worse prognosis and requires a different
      therapeutic approach. The differential diagnosis is based on the biopsy findings.
      Verrucous carcinoma of the penis carries a good prognosis and can be managed by
      conservative surgery (partial penectomy).

PMID- 11296681
TI  - Is aging a real risk factor for urological pathologies in men and women?
AB  - OBJECTIVE: With the progressive aging of the population in industrialized
      countries, urological pathologies are also increasing and creating a socio
      sanitary problem for the community. To investigate this problem we
      retrospectively analyzed a heterogeneous sample of 283 patients, 134 males and
      149 females who attended our urodynamics laboratory. METHODS: The female patients
      were subdivided into 6 categories and the male patients into 7 categories
      according to their urodynamic diagnoses. Their age distributions were compared
      with those of the population of the region of Lazio in Italy in order to
      calculate the "risk tendency". RESULTS AND CONCLUSIONS: The most frequent
      pathologies in males were bladder outlet obstruction (BOO) associated or not with
      detrusor overactivity (DO), and in females it was cystocele associated or not
      with DO or obstruction. There is a significant increase in these urological
      pathologies in older people. The relative risks for the females increase from age
      20-29, stabilize at around 50 to 69 years and decline thereafter. The risk
      approximately doubles every ten years of age from 20 to 50. At ages 50-69 the
      risk is about 8 or 9 times higher than the risk at age 20-29 and double that of
      women aged over 70 years. The risk for the males also approximately double for
      every ten years of age. Men aged 60-69 have about 25 times the risk of these
      pathologies than men aged 20-29, and in the oldest men, those over 70 years, the
      risk is almost 40 times as high.

PMID- 11296682
TI  - Can head injury patients simulate malingering?
AB  - In the past few years, there have been many simulation studies on the efficacy of
      symptom validation tests. These typically involved nonclinical participants. This
      line of research was limited because the impact of the experience of head injury
      was not examined. Researchers failed to understand whether individuals with head
      injury would feign cognitive deficits on symptom validation tests as well as
      their nonclinical counterparts did. This study was designed to investigate
      simulation of memory deficits among the head injured on the Portland Digit
      Recognition Test (PDRT; Binder, 1993). Head injury patients, with and without
      corroborated brain damage, and a group of controls were involved to resemble
      clinical populations. Results showed that false negative rates ranged from 67% to
      84% when participants were asked to feign memory difficulty on the PDRT. Head
      injury patients, regardless of corroboration of brain damage, were equally
      capable of feigning memory deficits on the PDRT as their nonclinical
      counterparts. Findings suggest that the additive value of symptom validity tests,
      such as the PDRT, can be limited for their use as malingering tests.

PMID- 11296683
TI  - Wechsler Adult Intelligence Scale-Revised Block Design broken configuration
      errors in nonpenetrating traumatic brain injury.
AB  - Final broken configuration errors on the Wechsler Adult Intelligence Scale
      Revised (WAIS-R; Wechsler, 1981) Block Design subtest were examined in 50
      moderate and severe nonpenetrating traumatically brain injured adults. Patients
      were divided into left (n = 15) and right hemisphere (n = 19) groups based on a
      history of unilateral craniotomy for treatment of an intracranial lesion and were
      compared to a group with diffuse or negative brain CT scan findings and no
      history of neurosurgery (n = 16). The percentage of final broken configuration
      errors was related to injury severity, Benton Visual Form Discrimination Test
      (VFD; Benton, Hamsher, Varney, & Spreen, 1983) total score and the number of VFD
      rotation and peripheral errors. The percentage of final broken configuration
      errors was higher in the patients with right craniotomies than in the left or no
      craniotomy groups, which did not differ. Broken configuration errors did not
      occur more frequently on designs without an embedded grid pattern. Right
      craniotomy patients did not show a greater percentage of broken configuration
      errors on nongrid designs as compared to grid designs.

PMID- 11296684
TI  - Construct validity and predictive value of the Hooper Visual Organization Test in
      stroke rehabilitation.
AB  - The Hooper Visual Organization Test (HVOT; Hooper, 1958) is a commonly used
      measure of visual perceptual function. However, serious questions have recently
      been raised about its construct validity (i.e., the role of object naming). This
      study further examined the HVOT's construct validity and began exploring its
      contribution to outcome prediction in stroke rehabilitation. Participants were
      101 rehabilitation inpatients suffering from recent cerebrovascular accidents.
      Each participant was administered the HVOT as part of a comprehensive
      neuropsychological evaluation. Wechsler Adult Intelligence Scale-Revised
      (Wechsler, 1981) Object Assembly, Picture Completion, and Cognistat Naming were
      significantly and uniquely correlated with the HVOT and accounted for about 45%
      of its variance. The HVOT's value in outcome prediction was examined by
      correlating HVOT with admission and discharge Functional Independence Measure
      (FIM; Granger & Hamilton, 1990; Hamilton, Granger, Sherwin, Zielezny, & Tashman,
      1987) scores. While correlating weakly with some FIM domains, when admission FIM
      was controlled, the relation between HVOT and discharge FIM became
      nonsignificant. Implications of these data for the HVOT's clinical utility are
      discussed.

PMID- 11296685
TI  - Cognitive intervention in unemployed individuals with reading and writing
      disabilities.
AB  - Sixty native-born Swedish unemployed participants with reading and writing
      disabilities (R&WD) participated in a 20-week educational program aimed at
      improving reading and writing, verbal memory, self-confidence, and flexibility of
      perspectives. They were tested with a comprehensive battery (interviews,
      questionnaires, neuropsychological tests, and tests of academic achievement)
      before and after the intervention. Sixteen controls, matched for sex, age,
      education, and nonverbal IQ, participated in the pre- and posttest sessions but
      received only standard unemployment interventions. The educational program
      participants' performance in tests assessing spelling, decoding of letters, self
      confidence, and flexibility improved significantly in comparison with the
      controls after the intervention. A significantly larger number of the
      participants had obtained work or started a regular education than expected. A
      substantial proportion of unemployed participants have R&WD and it appears that
      an intensive but fairly short educational program can improve their accessibility
      to the labor market and their motivation for study.

PMID- 11296686
TI  - Neural activation during performance of number-letter sequencing.
AB  - Recent advances in neuroimaging have enabled researchers to establish relatively
      specific areas of the brain that are involved in working memory. In this positron
      emission tomography study we examined the pattern of neural activation associated
      with performance on number-letter sequencing, a purported measure of working
      memory included in the new Wechsler scales for memory and intelligence. After
      controlling for basic audition, verbalization, and attention, areas of activation
      were observed in the orbital frontal lobe, dorsolateral prefrontal cortex, and
      posterior parietal cortex. This is highly consistent with reports from the
      literature on activation patterns associated with working memory. More activation
      peaks were observed in the right hemisphere, suggesting the participants utilized
      visualization of the verbal information. Consistent with task conceptualization,
      this study provides support for number-letter sequencing as a task involving
      working memory.

PMID- 11296687
TI  - Performance on original and a Chinese version of Trail Making Test Part B: a
      normative bilingual sample.
AB  - This study examined an equivalent of Trail Making Test Part B for native Chinese
      speakers. Digit Symbol Coding and Trail Making Test Parts A and B were
      administered to American and Chinese students from an American university. The
      Chinese group also took a modified Trails B test where numbers in Chinese
      characters replaced English letters. Independent-samples t tests showed no
      difference between American and Chinese groups on the Digit Symbol Coding and
      Trails A, but a difference on Trails B (p < .05). The Chinese group's modified
      Trails B performance showed no difference from the American group's original
      Trails B performance. These findings suggest equivalence of Digit Symbol Coding
      and Trails A for American and Chinese groups, but a longer Trails B completion
      time for the Chinese group. This finding indicates a language bias of Trails B
      for Chinese-English bilinguals. Thus, the Chinese version of Trails B is
      preferable for native Chinese speakers.

PMID- 11296688
TI  - Clinical normative data for the WCST-64 following uncomplicated mild head injury.
AB  - Clinical norms for the 64-item Wisconsin Card Sorting Test (WCST-64) are
      presented. The norms were derived from 303 persons presenting for emergency
      services who met criteria for uncomplicated mild head injury. Most data were
      obtained within 2 days of injury, and the remaining data were obtained within 10
      days of injury. The norms may be used to help determine whether or not a person's
      scores on the WCST-64 are typical of those seen shortly after sustaining an
      uncomplicated mild head injury.

PMID- 11296690
TI  - Fatty liver in liver transplantation and surgery.
AB  - Steatosis of the liver is common in Western countries, affecting about 25% of
      donors for liver transplantation and 20% of patients undergoing liver resection.
      Transplantation of livers with severe steatosis (> 60%) is associated with a high
      risk of primary nonfunction, and these livers should not be used for organ
      donation. In contrast, transplantation with livers containing mild steatosis (<
      30%) yields results similar to those of transplantation performed with nonfatty
      livers. The outcome of livers with moderate steatosis (30 to 60%) are varying,
      and the use of these organs depends on the existence of additional risk factors.
      Similarly, liver resection in patients with steatosis is associated with a risk
      of postoperative mortality when compared with patients with nonfatty livers (14%
      versus 2%). Although hepatic steatosis is an important risk factor for surgery,
      little is known about the mechanisms of injury. In animal experiments, steatosis
      is associated with decreased ATP production and a disturbance of sinusoidal flow.
      Further contributing factors may include Kupffer cell dysfunction and leukocyte
      adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a
      predominant necrotic form of cell death. In addition, the ability of hepatocytes
      to regenerate after major tissue loss is impaired in the steatotic liver. Very
      few protective strategies are known. Ischemic preconditioning and intermittent
      clamping protect the human liver against prolonged periods of ischemia. These
      techniques appear to be particularly protective in the steatotic liver. New
      insights into the mechanisms of liver failure in steatotic organs are needed to
      decrease the risk of surgery and increase the pool of organ donors.

PMID- 11296689
TI  - The Corsi Block-Tapping Task: standardization and normative data.
AB  - This article describes a standardized administration and scoring procedure for
      the widely used Corsi Block-Tapping Task, designed to assess the visual memory
      span. This method was applied in a group of healthy participants (n = 70) and a
      group of patients with cerebral lesions (n = 70), that were categorized on the
      basis of lesion location (left or right hemisphere, bilateral or subcortical).
      The percentile distribution as well as cutoff points on the basis of the control
      data are provided. It was found that 20% of the patients perform in the
      borderline range on this task, and over 8% have an impaired performance
      ("retarded"). In addition, right hemisphere patients performed worse than left
      hemisphere patients. These data show that the Corsi Block-Tapping Task can be
      effectively used to assess visuospatial short-term memory in patients with brain
      damage, and is selective for the side of the lesion.

PMID- 11296691
TI  - Hepatic Weber-Christian disease.
AB  - Weber-Christian disease is an idiopathic disorder characterized by nonsuppurative
      nodular panniculitis with a lobular distribution of acute inflammation in the
      subcutaneous fat with occasional systemic involvement. Although the
      histopathologic features of the liver disease in the syndrome are characterized
      by steatohepatitis, the clinical features have not been well defined. We report a
      case of hepatic Weber-Christian disease and discuss the clinical differences from
      steatohepatitis due to the more common disorders of obesity and diabetes
      mellitus.

PMID- 11296692
TI  - A 37-year-old male with hepatomegaly, neurologic and skin involvement associated
      with elevated urinary porphyrin excretion.

PMID- 11296693
TI  - Clinical features and natural history of nonalcoholic steatosis syndromes.
AB  - Nonalcoholic steatohepatitis, along with other forms of nonalcoholic fatty liver
      disease, is a chronic liver disease that is attracting increasing significance.
      It is a clinicopathologic syndrome that was originally described in obese,
      diabetic females who denied alcohol use but in whom the hepatic histology was
      consistent with alcoholic hepatitis. This typical patient profile has been
      expanded and is now recognized to occur even in normal weight males without overt
      abnormalities in carbohydrate metabolism. Although originally believed to be a
      benign clinical entity, nonalcoholic steatohepatitis is now recognized as a cause
      of progressive fibrotic liver disease with adverse clinical sequelae. It is
      important to emphasize that nonalcoholic steatohepatitis is best considered one
      type of a larger spectrum of nonalcoholic fatty liver disease that is a
      consequence of insulin resistance and ranges from fat alone to fat plus
      inflammation, fat plus ballooning degeneration, and nonalcoholic steatohepatitis,
      the latter being the most serious form. As with any disease, the clinical
      importance of nonalcoholic steatohepatitis is related to its prevalence and
      natural history. Recent studies using different methodologies indicate that in
      the general population the prevalence of fatty liver and nonalcoholic
      steatohepatitis is approximately 20% and 3%, respectively. These prevalence rates
      are increased in certain subpopulations such as obesity and type II diabetes. Of
      greater concern is the recognition that cirrhosis and liver-related deaths occur
      in approximately 20% and 8% of these patients, respectively, over a 10-year
      period. Risk factors for these adverse clinical symptoms include patients older
      than the age of 45, the presence of diabetes or obesity, an aspartate
      aminotransferase/alanine aminotransferase ratio > 1 and hepatic histology.
      However, a number of important unresolved issues must be clarified before the
      true natural history of this disease can be fully understood.

PMID- 11296695
TI  - Nonalcoholic steatohepatitis: definition and pathology.
AB  - Nonalcoholic steatohepatitis (NASH) is a significant form of chronic liver
      disease in adults and children. The natural history of NASH ranges from indolent
      to end-stage liver disease. Current studies are focusing on identification of
      histologic and/or clinical markers of progression. NASH may be an underlying
      cause of cryptogenic cirrhosis, and the lesions of NASH may recur in allograft
      livers. An expanding array of clinical conditions and pathogenetic mechanisms
      have been identified, but many cases remain "idiopathic"; lack of significant
      alcohol use is, by definition, common to all cases. Neither clinical evaluation
      nor laboratory values can ensure either the diagnosis or the exclusion of NASH,
      and liver biopsy interpretation continues to be considered the "gold standard"
      for diagnosis. The lesions in NASH are similar but not identical to those of
      alcoholic steatohepatitis; exact, specific histologic criteria for the diagnosis
      are currently under discussion. The lesions most commonly accepted for NASH
      include steatosis, hepatocyte ballooning degeneration, mild diffuse lobular mixed
      acute and chronic inflammation, and perivenular, perisinusoidal collagen
      deposition. Zone 3 accentuation may be detected. Mallory's hyaline, vacuolated
      nuclei in periportal hepatocytes, lobular lipogranulomas, and PAS-diastase
      resistant Kupffer cells are common. In biopsy specimens from children, portal
      inflammation may be more prominent than in adults. Progression of fibrosis may
      result in bridging septa and cirrhosis. The lesions of steatohepatitis may be
      noted concurrently with other forms of chronic liver disease. A histological
      "grading and staging" system has been developed to reflect the unique features of
      steatohepatitis, gradations of severity and fibrosis, and to promote uniform
      reporting of the histopathology.

PMID- 11296694
TI  - Etiopathogenesis of nonalcoholic steatohepatitis.
AB  - The definable causes of nonalcoholic steatohepatitis (NASH) include jejunoileal
      bypass surgery (JIB), other causes of rapid and profound weight loss in obese
      subjects, total parenteral nutrition, drugs, industrial toxins, copper toxicity,
      and disorders characterized by extreme insulin resistance. However, the
      etiopathogenesis in most cases of NASH appears multifactorial. Obesity, type 2
      diabetes, and hypertriglyceridemia are often associated with hepatic steatosis,
      and although this does not invariably lead to NASH, the fatty liver is vulnerable
      to hepatocellular injury initiated by reactive oxygen species (ROS). It is
      critical to understand not only the triggers for hepatitis (injury and
      inflammation) in NASH but also how this is perpetuated as chronic liver disease.
      The present focus is on whether the biochemical processes that generate oxidative
      stress lead to hepatocyte injury and secondary recruitment of inflammation or
      whether inflammation is the primary mediator of liver cell injury. Insulin
      resistance is a reproducible pathogenic factor in NASH. It favors accumulation of
      free fatty acids in the liver and predisposes to oxidative stress by stimulating
      microsomal lipid peroxidases and by the direct effects of high insulin levels in
      decreasing mitochondrial beta-oxidation. CYP2E1 is normally suppressed by insulin
      but is invariably increased in the livers of patients with NASH. In rodent
      dietary models of steatohepatitis, CYP2E1 is the catalyst of microsomal lipid
      peroxidation, while in Cyp 2e1 nullizygous mice, CYP4A proteins are induced and
      function as alternative microsomal lipid peroxidases. Other studies implicate
      activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) as
      leading to NASH; PPAR alpha is a transcription factor that governs both
      microsomal (via CYP4A) and peroxisomal (beta-oxidation) pathways of lipid
      oxidation and ultimately production of ROS. Increased lipid peroxidation is a
      crucial difference between the livers of rodents with experimental NASH and those
      of ob/ob genetically obese mice that have uncomplicated steatosis. Administration
      of endotoxin, through the release of tumor necrosis factor-alpha (TNF-alpha),
      provokes liver inflammation with hepatocyte injury in the steatotic liver. This
      may be particularly relevant in JIB and has been suggested as a pathogenic
      mechanism in primary NASH. It has been proposed that inheriting one or more
      copies of the hemochromatosis gene, C282Y, promotes fibrotic progression in NASH
      because of increased hepatic iron deposition, but recent studies have failed to
      confirm this. The relationship between the severity of hepatitis in NASH and
      progression to cirrhosis implies that products of the inflammatory infiltrate
      play a role in fibrogenesis. In summary, NASH can be regarded as the hepatic
      consequence of the metabolic syndrome (or syndrome X). Attention should now shift
      from steatosis, a generally benign process that is less evident in the advanced
      stages of cirrhosis, to the mechanisms for hepatocellular injury, inflammation,
      and hepatic fibrosis. In particular, the genetic, molecular, and cellular factors
      that ordain and moderate fibrosis in the context of steatohepatitis will be of
      greatest relevance to effective therapy and clinical outcome.

PMID- 11296696
TI  - Peroxisomal beta-oxidation and steatohepatitis.
AB  - Fatty acid beta-oxidation occurs in both mitochondria and peroxisomes.
      Mitochondria catalyze the beta-oxidation of the bulk of short-, medium-, and long
      chain fatty acids derived from diet, and this pathway constitutes the major
      process by which fatty acids are oxidized to generate energy. Peroxisomes are
      involved, preferentially, in the beta-oxidation chain shortening of very long
      chain fatty acids (VLCFAs) and in the process produce H2O2. Long-chain fatty
      acids and VLCFAs are also metabolized by the cytochrome P450 CYP4A omega
      oxidation system to toxic dicarboxylic acids (DCAs) that serve as substrates for
      peroxisomal beta-oxidation, and this process also leads to the production of
      superoxide and H2O2. The genes encoding peroxisomal, microsomal, and certain
      mitochondrial fatty acid metabolizing enzymes in liver are transcriptionally
      regulated by peroxisome proliferator-activated receptor alpha (PPAR alpha).
      Deficiencies of the enzymes of peroxisomal beta-oxidation have been recognized as
      important causes of disease. Evidence from mice deficient in PPAR alpha (PPAR
      alpha-/-), deficient in peroxisomal fatty acyl-CoA oxidase (AOX-/-), the first
      enzyme of the classical beta-oxidation system, and deficient in both PPAR alpha
      and AOX (PPAR alpha-/-AOX-/-) points to the critical importance of PPAR alpha
      inducible peroxisomal and microsomal oxidation systems that metabolize LCFAs and
      VLCFAs in the pathogenesis of nonalcoholic microvesicular hepatic steatosis and
      steatohepatitis. These and other mouse models should provide greater
      understanding of the molecular mechanism responsible for hepatic steatosis and
      steatohepatitis. Deficiency of AOX disrupts the oxidation of VLCFAs, DCAs, and
      other substrates leading to extensive microvesicular steatosis and
      steatohepatitis. Loss of this enzyme also causes sustained hyperactivation of
      PPAR alpha, leading to transcriptional up-regulation of PPAR alpha-regulated
      genes, indicating that unmetabolized substrates of AOX function as ligands of
      PPAR alpha. beta-Oxidation is the major process by which fatty acids are oxidized
      to generate energy, especially when glucose availability is low during periods of
      starvation. Mice deficient in PPAR alpha and those nullizygous for both PPAR
      alpha and AOX show a minimal steatotic phenotype under fed conditions but
      manifest an exaggerated steatotic response to fasting, indicating that defects in
      PPAR alpha-inducible fatty acid oxidation determine the severity of fatty liver
      phenotype to conditions reflecting energy-related stress.

PMID- 11296697
TI  - Mitochondria in steatohepatitis.
AB  - For the first time in history, populations in affluent countries may
      concomitantly indulge in rich food and physical idleness. Various combinations of
      obesity, diabetes, and hypertriglyceridemia, with insulin resistance as the
      common feature, cause hepatic steatosis, which can trigger necroinflammation and
      fibrosis. Patients with "primary" steatohepatitis exhibit ultrastructural
      mitochondrial lesions, decreased activity of respiratory chain complexes, and
      have impaired ability to resynthesize ATP after a fructose challenge.
      Mitochondria play a major role in fat oxidation and energy production but also
      leak reactive oxygen species (ROS) and are the main cellular source of ROS. In
      patients with steatosis, mitochondrial ROS may oxidize hepatic fat deposits, as
      suggested in animal models. Lipid peroxidation products impair the flow of
      electrons along the respiratory chain, which may cause overreduction of
      respiratory chain components, further increasing mitochondrial ROS formation and
      lipid peroxidation. Another vicious circle could involve ROS-induced depletion of
      antioxidants, impairing ROS inactivation. Blood vitamin E is decreased in some
      obese children with steatohepatitis, and serum transaminases improve after
      vitamin E supplementation. Steatohepatitis is also caused by alcohol abuse,
      drugs, and other causes. In "secondary" steatohepatitis, mitochondrial ROS
      formation is further increased as the causative disease itself directly increases
      ROS or first impairs respiration, which secondarily increases mitochondrial ROS
      formation. This "second hit" could cause more lipid peroxidation, cytokine
      induction, Fas ligand induction, and fibrogenesis than in primary
      steatohepatitis.

PMID- 11296698
TI  - Imaging of hepatic steatosis.
AB  - Hepatic steatosis is a common finding encountered during cross-sectional imaging
      examinations. This article reviews the imaging findings of hepatic steatosis as
      revealed by sonography, computed tomography, magnetic resonance imaging, and
      magnetic resonance spectroscopy. Focal fatty sparing and focal hepatic steatosis
      are conditions that can create potential diagnostic challenges for the
      radiologist. The typical findings, distribution, and etiology of these focal
      processes are presented. In the setting of diffuse hepatic steatosis, hepatic
      mass lesions can be difficult to discern on both computed tomography and
      sonography, with reported decreased sensitivity and specificity of lesion
      detection. In such cases, magnetic resonance imaging may be the imaging procedure
      of choice for the detection and characterization of both hepatic steatosis and
      coexistent hepatic masses. Some hepatocellular neoplasms, particularly hepatic
      adenoma and well-differentiated hepatocellular carcinoma, can have intratumoral
      lipid. By demonstrating the lipid content of these masses, imaging can add
      specificity in characterizing them as hepatocellular in origin because
      nonhepatocellular neoplasms in general do not contain intracellular lipid.

PMID- 11296699
TI  - Treatment of nonalcoholic fatty liver: present and emerging therapies.
AB  - Treatment of patients with nonalcoholic fatty liver has typically been focused on
      the management of associated conditions such as obesity, diabetes mellitus, and
      hyperlipidemia as well as discontinuation of potentially hepatotoxic drugs.
      Nonalcoholic fatty liver associated with obesity may resolve with weight
      reduction, although the benefits of weight loss have been inconsistent.
      Appropriate metabolic control for patients with diabetes mellitus or
      hyperlipidemia is always recommended but not always effective in reversing
      nonalcoholic fatty liver. Promising results of pilot studies evaluating
      ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, and alpha
      tocopherol suggest that these medications may be of potential benefit in the
      treatment of patients with nonalcoholic fatty liver. These medications, however,
      need first to be tested in well-controlled trials with clinically relevant end
      points and extended follow-up. A better understanding of the pathogenesis and
      natural history of this condition will help to identify the subset of patients
      with nonalcoholic fatty liver at risk of progressing to advanced liver disease
      and, hence, the subgroup of patients who should derive the most benefit from
      medical therapy. In this article, we review (1) the existing medical therapy for
      patients with nonalcoholic fatty liver, (2) the emerging data from clinical
      trials evaluating potentially useful medications, and (3) the potential
      therapeutic implications of recent studies on the pathogenesis of this liver
      disease.

PMID- 11296701
TI  - [Dynamics of instrumental reflex changes following transection of the
      corticospinal tract and ablation of the cerebral cortex sensorimotor region in
      rats].
AB  - Unilateral transection of bulbar pyramid performed prior to ablation of the
      ipsilateral sensomotor cortex was shown to facilitate recovery of operant
      conditioning and compensatory processes in rats. There was no such corticofugal
      plasticity in ablation of the sensomotor cortex alone. The phenomenon may be
      explained by switching of descending influences on the cortico-rubrospinal system
      through participation of the loop: corticorubral projection--red nucleus-
      inferior olive--cerebellum--thalamus--cerebral cortex.

PMID- 11296700
TI  - Animal models of steatosis.
AB  - The lipid content of hepatocytes is regulated by the integrated activities of
      cellular enzymes that catalyze lipid uptake, synthesis, oxidation, and export.
      When "input" of fats into these systems (either because of increased fatty acid
      delivery, hepatic fatty acid uptake, or fatty acid synthesis) exceeds the
      capacity for fatty acid oxidation or export (i.e., "output"), then hepatic
      steatosis occurs. Genetic causes of increased fatty acid input promote excessive
      hepatic lipogenesis. These include mutations that cause leptin deficiency or
      leptin receptor inhibition and mutations that induce insulin, insulin-like growth
      factors, or insulin-responsive transcription factors. Genetic causes of impaired
      hepatic fatty acid oxidation inhibit the elimination (i.e., output) of fat from
      the liver. These include mutations that inhibit various components of the
      peroxisomal and/or mitochondrial pathways for fatty acid beta-oxidation.
      Environmental factors, such as diets and toxins, can also unbalance hepatic fatty
      acid synthesis and oxidation. Hepatic lipogenesis is increased by dietary
      sucrose, fructose, or fats and certain toxins, such as ethanol. Hepatic fatty
      acid oxidation is inhibited by choline- or methionine-deficient diets and other
      toxins, such as etomoxir. Animals with genetic or environmental induction of
      hepatic lipogenesis appear to be useful models for human nonalcoholic fatty liver
      disease in which hyperinsulinemia and defective leptin signaling are conspicuous
      at early stages of the disease process.

PMID- 11296702
TI  - [Mechanisms of effects of adenosine and dopamine on modification of synapses in
      striato-nigral and striato-pallidal neurons].
AB  - On the basis of earlier suggested unitary mechanism of synaptic plasticity
      opposite effects of adenosine and dopamine on the cAMP concentration in striatal
      spinal cells can emphasize the well known antagonistic interactions between A2A
      and D2 receptors on striatopallidal cells and between A1 and D1 receptors on
      striatonigral cells. This is due to that both the dopamine agonist and adenosine
      antagonist must promote the induction of long-term potentiation/depression of
      efficacy of excitatory cortical inputs to striatopallidal/striatonigral cells.
      This modification must lead to synergistic disinhibition of thalamic cells via
      "direct" and "indirect" pathways through basal ganglia and subsequent
      strengthening of motor activity.

PMID- 11296703
TI  - [Impairement of estimation of the inner time and the emotional behavior in rats
      with the lesioned striatum and hippocampus].
AB  - Bilateral lesion of the striatum delayed time conditioning in rats, induced
      anxiety, rearranged normal correlation between the anxiety level and
      autochronometrical ability. These shifts progressed along with an augmentation of
      the striatum lesion extent. Combined striat- and hippocampectomy as well as the
      latter alone resulted in a complete absence of time counting learning
      irrespective of the brain lesion extent. In these animals anxiety was also more
      obvious.

PMID- 11296704
TI  - [Capsaicin-sensitive afferents in the vagus nerve].
AB  - Vanilloids were shown to interact with over 70% of vagal C-afferents first
      causing an excitation followed by desensitisation and a lasting destruction of
      nerve fibres. Capsaicin induces a secretion of some neuropeptides from 10-30% of
      vagal sensory terminals and therefore serves as a pharmacological tool for
      testing local "effector function" of primary afferents. Vagal afferents seem to
      have their own subtype of vanilloid receptors (VR), not completely identical with
      the VR receptors in the dorsal root ganglia. Considering potentiation of the
      capsaicin receptors sensitivity by some factors such as local heating, pH, free
      oxygen radicals, a possible role of the VRs as integrators of chemical and
      physical components of nociceptive stimuli, is discussed.

PMID- 11296705
TI  - [Neuron non-electrical functions].
AB  - Classical histological preparations of the metasympathetic nervous system treated
      with silver salts were compared with isolated neuron cultures to study non
      electrical functions of the neurons. A hypothesis of a tissue trophic effect of
      the nervous tissue's receptors, is advanced. Proteolytic enzymes were shown to be
      a growth factor for surrounding tissues and to play a role of trophic agents. A
      permanent restructurisation seems to occur in formed plexuses of adult healthy
      animals.

PMID- 11296706
TI  - [Peptidergic mechanisms of hypothermia-induced seizures in rats during early
      ontogenesis].
AB  - Arginine-vasopressin reduced the tonic-clonic seizures' latency as well as the
      duration of the seizures brain-stem generalisation on the 3rd and 5th postpartum
      days in rats. The reduced latency was also observed after the PACAP38 low doses
      administration, whereas higher doses diminished and then enhanced the threshold
      of generalised hyperthermia-induced seizures on the 3rd and 5th days and the 7th
      and 9th days, resp. The arginine-vasopressin-treated animals had a dramatically
      enhanced duration of the tonic-clonic seizures up to the epileptic status on the
      9th postpartum day. The findings suggest the PACAP involvement in mechanisms of
      experimental febrile seizures through its effect upon arginine-vasopressin
      neurosecretion.

PMID- 11296707
TI  - [Modifying effect of the repeated experience of agonistic confrontations on
      effect of naltrexone in male mice].
AB  - In mice with different experience of agonistic confrontations: victories or
      social defeats during 3 and 10 days (T3 and T10 winners and T3 and T10 losers,
      resp.), T10 winners displayed a lesser aggression and a more hostile behaviour
      than T3 winners. Naltrexone dose-dependently decreased attacks in the T3 winners
      and did not affect aggressive grooming, diggings, autogrooming, and exploratory
      activity. Naltrexone was ineffective in T10 winners. The naltrexone effects were
      similar in T3 and T10 losers and its high and low doses contrarily affected
      different parameters of submissive behaviour. The repeated experience of
      agonistic confrontations seems to modify the naltrexone effects depending on a
      neurochemical background, differing in winners and losers.

PMID- 11296708
TI  - [Myogenic reactions of the rat isolated mesenteric artery: effect of acidosis and
      the primary vessel tone].
AB  - Stretch of the rat mesenteric artery ring pretreated with noradrenaline evoked a
      myogenic response consisting of the fast and slow phases which were maximal at
      about 3.5 and 45.1 s after the stretch, resp. Hypercapnic acidosis inhibited both
      phases of the response. Role of Ca2+ in origin of the two phases is discussed.

PMID- 11296709
TI  - [Effect of strophanthin on the electrophoretic mobility of blood erythrocytes in
      adults and children].
AB  - As assessed by changes in the erythrograms asymmetry coefficient, selectivity of
      the strophantin effect on cell populations with different mobility and age
      specifics of reciprocal responses, was revealed in adult subjects and in
      children. The data obtained suggest existence of difference in quality of
      functional condition of the erythrocytes with normal as well as reduced mobility
      in children and in adults.

PMID- 11296710
TI  - [Response of pial arterioles to alveolar hypercapnia in normotensive and
      hypertensive rats].
AB  - In the WKY rats, a large number of vessels were dilated in response to alveolar
      hypercapnia, the rest of the vessels remaining unchanged, whereas both
      vasodilation and vasoconstriction occurred under the same conditions in the SHR
      rats. The difference seems to be due to biophysical and/or biochemical specifics
      of the SHR vascular walls and to partially depend on specific features of
      haemodynamics in pial vascular micromodules in both strains of rats.

PMID- 11296711
TI  - [Visual evoked potentials in response to dichoptic presentation of sinusoidal
      grating and noise background].
AB  - Dichoptic stimulation was used in comparison of visual evoked potentials (VEPs)
      with those obtained with monocular stimulation (recordings made from the
      occipital area). 16 subjects viewed sinusoidal gratings with the right eye while
      a visual noise was added via a mirror for the left eye. In presence of the noise,
      amplitude of the early VEP components' N1, P1b, and the late component P2
      decreased, P1a is not changed in presence of the noise, and the late negative
      wave N2 increased for all spatial frequencies. The effect of noise on the
      amplitude of VEPs obtained for monocular and dichoptic stimulation was similar.
      The data suggest that external noise is filtered by the V1 cortical neurons-
      matched filters for the gratings.

PMID- 11296712
TI  - [Carbohydrate absorption in the rat small intestine following ligation of the
      bile duct].
AB  - Active transport of free glucose, and glucose released from maltose and starch
      hydrolysis (F-, M-, and S-glucose, respectively) was investigated in vitro in the
      rat small intestine 7 and 14-17 days after the ligation of the common bile duct
      or after the laparotomy (control). The relative role of the ileum (its proximal
      portion in particular) in active transport of F- and M-glucose was enhanced
      following ligation of the common bile duct as compared with the control
      (laparotomy). The active transport of S-glucose was relatively low in the control
      and actually absent after the ligation of the common bile duct. The findings seem
      to reflect adaptive-compensatory responses of intestinal mucous membrane to
      insufficiency of the lumen digestion of carbohydrates due to exclusion of bile
      from the process.

PMID- 11296713
TI  - [Determination of the lung functional residual capacity with Genchi and Schtange
      tests in humans].

PMID- 11296714
TI  - [A technique for the continuous recording the digestive tract evacuatory
      function].

PMID- 11296715
TI  - Smoothing enhances the detection of common structure from multiple time series.
AB  - The effects of smoothing (i.e., temporal averaging) on the detection of
      intraindividual interdependency from between-subjects aggregated (i.e., multiple)
      bivariate time series were examined. A simple moving average smoother was applied
      to different types of simulated processes that included error. The results
      indicated that smoothing facilitates the detection of common intraindividual
      structure from multiple time series. The efficacy of smoothing was dependent on
      the characteristics of the underlying process. It is suggested that smoothing
      increases the efficiency of the detection of common structure by increasing the
      signal-to-noise ratio (i.e., temporal reliability) of the time series. The issue
      and application of smoothing is further discussed in terms of signal extraction
      and classical test theory.

PMID- 11296716
TI  - DifScal: a tool for analyzing difference ratings on an ordinal category scale.
AB  - An algorithm for analyzing difference scaling results is described. Frequency
      data on ordered categories that represent perceived differences for a
      unidimensional psychological attribute are modeled according to Thurstone's
      judgment scaling model. The algorithm applies the gradient method for the maximum
      likelihood estimation of the model parameters. Two ways to calculate the start
      configuration for the model parameters are elaborated. The algorithm also
      provides asymptotic values for the standard errors of the estimates and three
      measures for the goodness of the model fit. An additional features of DifScal is
      that it is suited to analyze incomplete data.

PMID- 11296717
TI  - Place learning in virtual space. III: Investigation of spatial navigation
      training procedures and their application to fMRI and clinical neuropsychology.
AB  - This paper describes the utilization of a desktop virtual environment task, the
      Computer-Generated (C-G) Arena, in the study of human spatial navigation. First,
      four experiments examined the efficacy of various training procedures in the C-G
      Arena. In Experiment 1, participants efficiently located a hidden target after
      only observing the virtual environment from a fixed position (placement
      learning). In Experiment 2, participants efficiently located a hidden target
      after only observing an experimenter search the virtual environment
      (observational learning). In Experiment 3, participants failed to display a
      latent learning effect in the virtual environment. In Experiment 4, all training
      procedures effectively taught participants the layout of the virtual environment,
      but the observational learning procedure most effectively taught participants the
      location of a hidden target within the environment. Finally, two experiments
      demonstrated the application of C-G Arena procedures to neuroimaging (Experiment
      5) and neuropsychological (Experiment 6) investigations of human spatial
      navigation.

PMID- 11296718
TI  - Estimating the minimum grip force required when grasping objects under impulsive
      loading conditions.
AB  - As an aid to studying the efficiency of grip force scaling in the context of
      collisions, we present a simple cost-effective approach to estimating the slip
      ratio--that is, the minimum grip-to-load-force ratio needed to prevent object
      slippage. The grip apparatus comprises a sturdy load cell to measure grip force
      and two linear potentiometers to provide detailed description of finger
      movements. The slip ratio was estimated by plotting the magnitude of finger
      movement against the grip-to-load-force ratio at the time of impact. The slip
      ratio was dependent on the direction of loading, which stresses the importance of
      estimating slip ratios in a context similar to that of the experiment in which
      the efficiency of subjects' behavior is to be assessed.

PMID- 11296719
TI  - User-controlled photographic animations, photograph-based questions, and
      questionnaires: three Internet-based instruments for measuring drivers' risk
      taking behavior.
AB  - The Internet has been exploited successfully in the past as a medium for
      behavioral research. This paper presents a series of studies designed to assess
      Internet-based measures of drivers' risk-taking behavior. First, we compared
      responses from an Internet sample with a traditional pencil-and-paper sample
      using established questionnaire measures of risk taking. No significant
      differences were found. Second, we assessed the validity of new Internet-based
      instruments, involving photographs and photographic animations, that measured
      speed, gap acceptance, and passing. Responses were found to reflect known
      demographic patterns of actual behavior to some degree. Also, a roadside survey
      of speeds was carried out at the locations depicted in the photographic measure
      of speeding and, with certain exceptions, differences between the two appeared to
      be constant. Third, a between-subject experimental manipulation involving the
      photographic animation measure of gap acceptance was used to demonstrate one
      application of these techniques.

PMID- 11296720
TI  - Techniques for the production of point-light and fully illuminated video displays
      from identical recordings.
AB  - Illumination of only a few key points on a moving human body or face is enough to
      convey a compelling perception of human motion. A full understanding of the
      perception of biological motion from point-light displays requires accurate
      comparison with the perception of motion in normal, fully illuminated versions of
      the same images. Traditionally, these two types of stimuli (point-light and fully
      illuminated) have been filmed separately, allowing the introduction of
      uncontrolled variation across recordings. This is undesirable for accurate
      comparison of perceptual performance across the two types of display. This
      article describes simple techniques, using proprietary software, that allow
      production of point-light and fully illuminated video displays from identical
      recordings. These techniques are potentially useful for many studies of motion
      perception, by permitting precise comparison of perceptual performances across
      point-light displays and their fully illuminated counterparts with accuracy and
      comparative ease.

PMID- 11296721
TI  - FTAP: a Linux-based program for tapping and music experiments.
AB  - This paper describes FTAP, a flexible data collection system for tapping and
      music experiments. FTAP runs on standard PC hardware with the Linux operating
      system and can process input keystrokes and auditory output with reliable
      millisecond resolution. It uses standard MIDI devices for input and output and is
      particularly flexible in the area of auditory feedback manipulation. FTAP can run
      a wide variety of experiments, including synchronization/continuation tasks (Wing
      & Kristofferson, 1973), synchronization tasks combined with delayed auditory
      feedback (Aschersleben & Prinz, 1997), continuation tasks with isolated feedback
      perturbations (Wing, 1977), and complex alterations of feedback in music
      performance (Finney, 1997). Such experiments have often been implemented with
      custom hardware and software systems, but with FTAP they can be specified by a
      simple ASCII text parameter file. FTAP is available at no cost in source-code
      form.

PMID- 11296722
TI  - Age of acquisition and imageability ratings for a large set of words, including
      verbs and function words.
AB  - Age of acquisition and imageability ratings were collected for 2,645 words,
      including 892 verbs and 213 function words. Words that were ambiguous as to
      grammatical category were disambiguated: Verbs were shown in their infinitival
      form, and nouns (where appropriate) were preceded by the indefinite article (such
      as to crack and a crack). Subjects were speakers of British English selected from
      a wide age range, so that differences in the responses across age groups could be
      compared. Within the subset of early acquired noun/verb homonyms, the verb forms
      were rated as later acquired than the nouns, and the verb homonyms of high
      imageability nouns were rated as significantly less imageable than their noun
      counterparts. A small number of words received significantly earlier or later age
      of acquisition ratings when the 20-40 years and 50-80 years age groups were
      compared. These tend to comprise words that have come to be used more frequently
      in recent years (either through technological advances or social change), or
      those that have fallen out of common usage. Regression analyses showed that
      although word length, familiarity, and concreteness make independent
      contributions to the age of acquisition measure, frequency and imageability are
      the most important predictors of rated age of acquisition.

PMID- 11296723
TI  - Regional variation of cloze probabilities for sentence contexts.
AB  - In 1980, Bloom and Fischler published a paper describing a set of sentence
      contexts (SCs) and their cloze probabilities (CPs). This material has
      subsequently been employed in numerous studies of linguistic processing. We
      sought to define the completion words and their CPs for Bloom and Fischler's
      sentences in an inner-city British population in order to establish reliable
      norms for subsequent studies in the U.K. One hundred and fifty incomplete SCs
      were presented to 73 volunteers. The CPs for each of the words used to complete
      the SCs were computed. We then compared the CPs from our sample with those from
      Bloom and Fischler. There were significant differences between CPs from each
      sample in 14% of the SCs analyzed (p < .01). Our data suggest that studies
      employing SCs and CPs may require locally defined norms if the test population
      differs substantially from the original one. The consequences of employing SCs
      and CPs to study linguistic processing without normalization are discussed.

PMID- 11296724
TI  - Lopinavir/ritonavir.
AB  - Treatment Review is intended to inform and update nurses about treatments
      relevant to HIV/AIDS. Product information presented in this column does not imply
      endorsement by the Association of Nurses in AIDS Care.

PMID- 11296726
TI  - HIV resistance backgrounder.

PMID- 11296725
TI  - WIDETIME: an HIV Odyssey and hopes and fears: Rusti's story.

PMID- 11296727
TI  - Emerging infections: relevance to HIV/AIDS care.

PMID- 11296728
TI  - Adult grief reactions following a sibling's death from AIDS.
AB  - The AIDS epidemic has resulted in an unprecedented death toll among young adults,
      many of whom are survived by siblings. Whereas the circumstances surrounding
      deaths from AIDS place survivors at risk for intense bereavement, no reported
      studies have examined the pattern or intensity of grief among adult siblings. One
      hundred and two adults who had experienced the death of a sibling from AIDS were
      recruited into this study in which grief reactions were measured using the Grief
      Experience Inventory. Time since the sibling's death ranged from 3 months to 11
      years. Grief reactions were found to exceed those previously reported. A positive
      relationship was found between the level of closeness of the survivor to the
      deceased and the intensity of grief reactions. No relationship was found between
      time since the sibling's death and intensity of grief.

PMID- 11296729
TI  - Negotiating trust: a grounded theory study of interpersonal relationships between
      persons living with HIV/AIDS and their primary health care providers.
AB  - This grounded theory study is an exploration of long-term interpersonal
      relationships between patients and their primary health care providers, including
      physicians and nurse practitioners, in an urban outpatient HIV/AIDS clinic. Many
      providers believe that the positive interpersonal relationship enhances the
      health care experience for the patient, but there is a scarcity of research in
      this area. Persons who are patients were interviewed (N = 14) to look at these
      relationships from their points of view and develop theory to guide clinicians in
      forming such relationships. Theoretical sampling was used to find patients in
      this clinic population involved in long-term relationships with their providers.
      Open-ended interviews were conducted. These data were coded using the grounded
      theory method of constant comparative analysis. A basic process of negotiating
      trust was identified. Trust in these relationships is a state that is dynamic,
      volatile, and constantly renegotiated during the trajectory of the relationship
      through time. The trusting relationship is personally supportive for patients and
      may be a factor in the satisfaction found among health care providers in this
      clinical field despite the nature of this epidemic.

PMID- 11296730
TI  - Bearing witness to suffering in AIDS: constructing meaning from loss.
AB  - The phenomenon of AIDS volunteerism has been described as an act of bearing
      witness. It has been suggested that bearing witness assists individuals affected
      by the suffering in HIV/AIDS to heal. The purpose of this research was to explore
      AIDS volunteerism as a potentially healing phenomenon. Using grounded theory
      methodology, open-ended interviews were conducted with 17 participants over a 7
      month period of time. The constant comparative method was used for data analysis.
      A substantive theory was generated that identified the basic sociological process
      as constructing meaning from loss and described the transformative psychosocial
      and spiritual healing process individuals undergo as they volunteer. Constructing
      meaning from loss is described within the following three major stages: (a)
      experiencing suffering, (b) containing suffering, and (c) transforming suffering.
      Characteristics within each stage are described. Suffering and complex loss are
      major issues in HIV/AIDS. Interventions are recommended for nurses who care for
      those affected by HIV disease.

PMID- 11296731
TI  - The sexual behaviors of African American women living with HIV disease: is
      perceived HIV status altering sexual behavior?
AB  - The purpose of the study was to compare the sexual risk behaviors of heterosexual
      African American women living with HIV disease to women who perceive themselves
      to be HIV negative using a comparative descriptive design. Data were collected
      using a demographics questionnaire developed by the investigator and the Safe Sex
      Behavior Questionnaire (SSBQ). The HIV-positive sample was collected in two
      public service agencies that provide case management for HIV-positive
      individuals. The HIV-negative sample was collected in the surrounding community,
      populated primarily by low-income African Americans. The HIV-positive group
      demonstrated lower levels of income and education. Scores on the SSBQ indicated
      no statistical difference between the high-risk sexual behaviors of the HIV
      positive and HIV-negative groups. No statistically significant difference was
      found in the reported past sexual experiences of the two groups, although mean
      SSBQ scores were higher in the HIV-positive group. The levels of sexual behaviors
      in both groups were consistent with the high-risk sexual behaviors of HIV
      negative persons reported in the literature. This illustrates the need for
      nursing as a profession to improve programs directed toward altering the
      behaviors of those at high risk of contracting or transmitting HIV disease.

PMID- 11296732
TI  - The effectiveness of self-management training for individuals with HIV/AIDS.
AB  - This study tested the effects of a 7-week individual self-management and coping
      skills training program on various measures of health and well-being of persons
      with HIV/AIDS. Forty men and women were randomly assigned the treatment or wait
      list control group. Treated participants showed significant posttreatment changes
      on all four major measures of mood, coping, and health attitudes. Treatment
      significantly improved coping strategies as measured by the use and effective
      measures of the Jalowiec Coping Scale and several of its subscales, including
      decreases in use of emotive, fatalistic, and palliative coping styles.
      Psychological mood was improved, as measured by the Profile of Moods Total Mood
      Disturbance (POMS TMD) score and specific subscales of the POMS, which were
      targeted in the intervention (e.g., Anger). Treated participants also showed
      significant increases on the Internal subscale of the Health Attribution Test.

PMID- 11296733
TI  - Voluntary caregivers' observations on the dynamics of hope across the continuum
      of HIV/AIDS: a focus group study.
AB  - The purpose of this study was to describe voluntary caregivers' observations on
      the dynamics of hope across the continuum of HIV/AIDS. Three focus group
      interview sessions were conducted with 10 voluntary caregivers in 1998. The data
      were analyzed using the grounded theory method described originally by Glaser and
      Strauss. Closing and opening emerged as the core categories in the dynamics of
      hope. Closing means closing down in despair and to the process of life, whereas
      opening means opening up to hope and the process of life. Nursing interventions
      that prevent closing and enable opening are helpful for these people. Conceptual
      clarification and the differentiation between the concepts of hope, wish,
      despair, and hopelessness presented in this study require further elaboration.
      Further research on the dynamics of hope in fearing HIV/AIDS or living with
      HIV/AIDS and being a significant other to a person with HIV/AIDS from different
      perspectives is also needed.

PMID- 11296734
TI  - Effects of estrogen deficiency on brain function. Implications for the treatment
      of postmenopausal women.
AB  - A growing body of evidence suggests that postmenopausal estrogen deficiency
      accelerates brain aging and increases the risk of various neurodegenerative
      processes, including Alzheimer's disease. Recent preclinical and clinical studies
      have indicated that estrogen has positive effects on brain homeostasis by
      preserving neural plasticity and the neurotransmitter pathways involved in
      learning, memory, and balance. In this article, Dr Birge and his coauthors
      address the effects of estrogen on brain function and discuss their implications
      for the use of selective estrogen receptor modulators, particularly tamoxifen and
      raloxifene, in postmenopausal women.

PMID- 11296735
TI  - SERMs and cardiovascular disease in women. How do these agents affect risk?
AB  - The beneficial effects of SERMs, specifically tamoxifen in the treatment and
      prevention of breast cancer and raloxifene in the prevention of osteoporosis, are
      well established. In addition, numerous groups of investigators have reported
      that these agents have a positive impact on cardiovascular health, possibly as a
      result of their cholesterol-lowering and anticoagulation actions. Although
      studies clearly showed that tamoxifen therapy improved the levels of some types
      of lipids, the changes did not appear to translate into a decreased risk of
      cardiovascular disease. However, the risk of thromboembolic events (as well as
      endometrial cancer) was increased with the use of tamoxifen, which is often
      prescribed for breast cancer prevention in healthy women. Similarly, raloxifene
      treatment had modest positive effects on cardiovascular risk factors but was
      associated with an increased risk of thromboembolism. When viewed as a whole,
      study results dictate that the benefits of SERM use for the prevention of
      cardiovascular disease be carefully weighed against the potential risks.

PMID- 11296736
TI  - Selective estrogen receptor modulators. An aid in unraveling the links between
      estrogen and breast cancer.
AB  - Breast cancer is a classic hormone-dependent malignant disease that is influenced
      by estrogen. However, the molecular links between estrogen and cell proliferation
      in healthy and malignant breast tissue are complex and as yet not well
      understood. The selective estrogen receptor modulators (SERMs), which are
      competitive inhibitors of estrogen binding at estrogen receptors alpha and beta,
      have become important weapons in the prevention and treatment of breast cancer.
      These agents also offer opportunities for the elucidation of the multiple
      molecular mechanisms by which estrogen affects cell proliferation. Each SERM
      estrogen receptor complex has a unique structure that influences its activity in
      different body tissues. Unraveling the links between SERM structure and function
      not only may shed light on the signaling pathways that connect estrogen to cell
      proliferation but also may allow the design of new agents specifically targeted
      to affect certain events along these pathways.

PMID- 11296737
TI  - Ecological risk assessment for agricultural pesticides.

PMID- 11296738
TI  - Determination of (mono-, di- and) tributyltin in sediments. Analytical methods.
AB  - Methods for the reliable determination of butyltin compounds in sediments are
      required for both national and international marine monitoring programmes. This
      evaluation of current commonly used approaches to the analysis identifies
      critical aspects of extraction, derivatisation, clean-up, separation,
      standardisation and detection with the objective of improving the analytical
      capabilities both of experienced laboratories and of those addressing the
      problems for the first time.

PMID- 11296739
TI  - Adsorption and removal of oxo-anions of arsenic and selenium on the zirconium(IV)
      loaded polymer resin functionalized with diethylenetriamine-N,N,N',N'-polyacetic
      acid.
AB  - A polymer adsorbent in which a Zr(IV)-edta complex analogue is immobilized has
      been prepared and applied to the removal of oxo-anions of As(III), As(V) and
      Se(IV). Effective retention of these anions has been demonstrated with the
      proposed polymer complex system. The adsorption mechanism of oxo-anions onto the
      Zr(IV)-chelated polymer complex has been investigated using Zr(IV)-edta as the
      model compound. The formation of mixed complexes with oxo-anions has been
      exemplified by the isolation of the carbonato complex K2[Zr(CO3)edta].3H2O, the
      structure of which has been confirmed by X-ray crystallography. NMR study
      suggests that oxo-anions that form weak or moderate conjugate acids, including
      those of As(III), As(V) and Se(IV), can form mixed complexes with Zr(IV)-edta
      using the unsaturated coordination site. However, oxo-anions of strong conjugate
      acids did not show any appreciable interaction with this complex. According to
      these observations, retention of oxo-anions on the Zr(IV)-chelated polymer
      complex has been interpreted by a ligand substitution reaction. The adsorption
      characteristics of As(III), As(V) and Se(IV) on the Zr(IV)-loaded resin have been
      examined with respect to the equilibrium adsorption, percentage extraction and
      the effect of co-existing ions. The adsorption and desorption cycles of the oxo
      anions have been demonstrated using a column packed with the proposed resin
      without any loss of column performance, which indicates the possibility for
      repeated use.

PMID- 11296740
TI  - A wireless, remote query magnetoelastic CO2 sensor.
AB  - This paper presents a wireless, passive, remote query CO2 sensor comprising a
      ribbon-like magnetoelastic thick-film coated with a mass-changing CO2 responsive
      polymer synthesized from acrylamide and isooctylacrylate. In response to a
      magnetic field impulse, the magnetostrictive magnetoelastic sensor vibrates at a
      characteristic resonant frequency that is inversely dependent upon the mass of
      the attached CO2 responsive polymer. The mechanical vibrations of the
      magnetostrictive sensor launch magnetic flux, which can be detected remotely
      using a pickup coil. By monitoring the resonant frequency of the passive sensor,
      the atmospheric CO2 concentration can be determined without the need for physical
      connections to the sensor or specific alignment requirements. The effect of
      humidity and the CO2 responsive copolymer composition on the measurement
      sensitivity are reported. Greatest sensitivity is achieved with a polymer
      comprising a 1:1 mole ratio of acrylamide to isooctyl acrylate. A 0.7% change in
      atmospheric CO2 concentration can be detected for a 20 microns thick polymer
      coated sensor.

PMID- 11296741
TI  - Structural characterisation of macromolecular organic material in air particulate
      matter using Py-GC-MS and solid state 13C-NMR.
AB  - Organic air particulate matter was analysed by applying the techniques of Py-GC
      MS (pyrolysis-gas chromatography-mass spectrometry) and solid state 13C-NMR
      (nuclear magnetic resonance). Particles dislodged from air particulate filters
      and humic acid extracted from these filters were studied for structural
      components. The structural components of the air particles and extracted humic
      acid consisted of compounds originating from biomacromolecules, namely, lignin,
      carbohydrates, protein and lipids. The main components identified for each class
      included: (1) methoxyphenols originating from lignin; (2) furans, aldehydes and
      ketones from carbohydrates; (3) pyrrole, indoles from protein; and (4) many
      hydrocarbons from lipid structures. Single ion monitoring (SIM) and tetramethyl
      ammonium hydroxide (TMAH) methylation were utilised for detection of aliphatic
      hydrocarbons and acidic components, respectively. Hydrocarbons ranging from C9 to
      C28 were detected by SIM analysis, while aliphatic acids ranged from C9 to C18.
      The majority of components analysed directly in the air particles were similar to
      those from the humic acid extracts. Many of the structural components of air
      particles were typical of humic substances of soil and aqueous systems and these
      were attributed to both biogenic and anthropogenic sources.

PMID- 11296743
TI  - Influence of reagent purity on the ion chromatographic determination of bromate
      in water using 3,3'-dimethoxybenzidine as a prochromophore for photometric
      detection.
AB  - Variable availability of the purified dihydrochloride salt of 3,3'
      dimethoxybenzidine (DMB; ortho-dianisidine) led us to investigate the effects of
      reagent purity on the analytical results obtained when this reagent is used in
      the photometric determination of the disinfection byproduct bromate. After
      analyte ions are separated by ion chromatography, a solution of DMB (post-column
      reagent) is added to the eluate and the DMB is oxidized, thereby producing a
      chromophore detected by its absorbance. Although some commercial products of
      undefined grade performed well, others did not. Variability was also observed
      between lots of purified material. Sensitivity at low concentrations (< 5
      micrograms L-1 BrO3-) varied by a factor of up to 10. In some cases, the lower
      limit of detection for photometric detection was greater than that obtained using
      conductivity detection, as high as 5-7 micrograms L-1 BrO3-. An impurity or
      several impurities are suspected to be responsible for deviations from linearity
      at low analyte concentrations. This investigation underscores the need for
      ensuring reagent purity in environmental analyses. Ideally, chemical
      manufacturers will meet the needs of analytical chemists who test potable water
      and begin producing a high grade material in sufficient quantities to meet
      monitoring requirements. The establishment of third-party standards for a
      spectrophotometric grade of DMB.2HCl would be helpful in ensuring that a variety
      of manufacturers could supply products of uniformly high quality that would be
      suitable for the measurement of bromate in public drinking water supplies.

PMID- 11296742
TI  - Colorimetric determination of formaldehyde in air using a hanging drop of
      chromotropic acid.
AB  - A simple and sensitive method to determine parts per billion (ppb) of atmospheric
      formaldehyde in situ, using chromotropic acid, is described. A colorimetric
      sensor, coupled to a droplet of 15.5 microL chromotropic acid, was constructed
      and used to sample and quantify formaldehyde. The sensor was set up with two
      optical fibers, a light emitting diode (LED) and two photodiodes. The reference
      and transmitted light were measured by a photodetection arrangement that converts
      the signals into units of absorbance. Air was sampled around the chromotropic
      acid droplet. A purple product was formed and measured after the sampling
      terminated (typically 7 min). The response is proportional to the sampling
      period, analyte concentration and sample flow rate. The detection limit is
      approximately 2 ppb and can be improved by using longer sampling times and/or a
      sampling flow rate higher than that used in this work, 200 mL min-1. The present
      technique affords a simple, inexpensive near real-time measurement with very
      little reagent consumption. The method is selective and highly sensitive. This
      sensor could be used either for outdoor or indoor atmospheres.

PMID- 11296744
TI  - Feasibility study prior to the certification of trace elements in urban and
      industrial wastewater reference materials.
AB  - Reliable results for the determination of trace elements in urban and industrial
      wastewaters are of paramount importance for both checking the performance of
      sewage treatment and for detecting possible urban or industrial contamination
      sources. The quality control of measurements should in principle rely on external
      tools such as certified reference materials (CRM), which should represent, as
      closely as possible, the matrix of samples currently analysed, e.g., in the frame
      of environmental monitoring. To date, however, no CRM representatives of
      wastewater composition are available, which limits the possibility for control
      laboratories to check their QC externally. To fill this gap, the European
      Commission's Standards, Measurements and Testing Programme (formerly BCR) has
      started a European collaborative project of which the aim is to test the
      feasibility of preparation of wastewater reference materials and the analytical
      state-of-the-art to enable the certification of trace elements in such matrices.
      This paper presents the results of the first phase of this project, namely the
      feasibility study and the results of an interlaboratory trial.

PMID- 11296745
TI  - Degradation of chlortoluron in water disinfection processes: a kinetic study.
AB  - The kinetics of the reaction between chlortoluron, a phenylurea herbicide [N'-(2
      hydroxy-4-methyl-5-chlorophenyl)-N,N-dimethylurea], and hypochlorite, the active
      species in water disinfection processes involving chlorine, were investigated by
      HPLC-UV and HPLC-electrospray ionisation mass spectrometry (HPLC-ESI-MS). In
      particular, the concentrations of the main chlortoluron by-products were
      monitored as a function of time by HPLC-ESI-MS and a kinetic model was developed
      to fit the relevant curves. The results showed that chlortoluron degradation
      starts with two parallel pathways, namely, chlorination and hydroxylation of the
      aromatic ring, which are then followed by consecutive chlorination reactions, and
      after almost 2 weeks by ring opening and partial mineralisation, as confirmed by
      head-space solid-phase microextraction gas chromatography-MS (SPME-GC-MS) and
      total organic carbon (TOC) measurements. Kinetic constants for the first
      reactions of the overall process, under pseudo-first-order conditions
      (hypochlorite excess), were estimated by a fitting procedure.

PMID- 11296746
TI  - Duplex RT-PCR for simultaneous detection of hepatitis A and hepatitis E virus
      isolated from drinking water samples.
AB  - A duplex reverse transcription polymerase chain reaction (RT-PCR) protocol for
      simultaneous detection of hepatitis A virus (HAV) and hepatitis E virus (HEV) in
      water samples has been developed and demonstrated. Both HAV and HEV were
      concentrated from drinking water samples through a one-step concentration
      protocol. Different cDNA could be produced in the RT step carried out with a
      random primer in a single reaction tube. Two different sets of primers specific
      for HAV-cDNA and HEV-cDNA were used for PCR amplification. Amplified DNA products
      representing HAV and HEV were identified by gel electrophoresis at 247 and 327 bp
      (base pair) sequences, respectively. Specific sets of primers amplified a single
      type of virus and no cross-reactivity of the primers was noticed in duplex RT
      PCR. The protocol was used for direct isolation and detection of HAV and HEV from
      23 water samples in urban areas of Chennai city. Out of these, nine water samples
      were positive for HAV, and three for HEV. All three samples positive for HEV were
      also positive for HAV. The test provides a rapid and economical means of water
      quality surveillance to specifically detect HAV and HEV.

PMID- 11296747
TI  - Chlorobiphenyl contaminants at Pladda and Garroch Head in the Firth of Clyde in
      relation to sewage sludge input.
AB  - Sewage sludge dumped at Garroch Head in the Firth of Clyde contains significant
      quantities of chlorinated hydrocarbons, such as polychlorinated biphenyls (CBs).
      These compounds are lipophilic and resistant to degradation. They accumulate in
      the biota either from the water column or through the food chain, particularly in
      tissue with a high lipid content. Bottom dwelling fish, such as plaice, in the
      vicinity of the dump site will accumulate CBs from their environment. Eighteen of
      the 209 CBs were measured in plaice livers from the Garroch Head dump site and
      from Pladda, a site reasonably remote from the dump site but also in the Clyde,
      over a 7 year period prior to the cessation of dumping in December 1998.
      Concentrations of the congeners in the liver of fish caught at the dump site
      were, in general, higher than those in the liver of fish caught at Pladda.
      Concentrations in the plaice livers for the sum of 18 CBs ranged from 1611 to
      8471 micrograms kg-1 lipid for Garroch Head samples and from 336.9 to 2635
      micrograms kg-1 lipid for samples from Pladda. The data were evaluated using
      principal component analysis (PCA). Pattern analysis was undertaken by
      normalising to the recalcitrant CB 153. Livers from the dump site were found to
      have a higher proportion of the lower chlorinated CBs. CB patterns were similar
      at the Garroch Head dump site from year to year, but multivariate techniques
      showed that there were differences in pattern when normalised to CB 153.

PMID- 11296748
TI  - A study on the behaviour of pesticides and their transformation products in the
      Scheldt estuary using liquid chromatography-electrospray tandem mass
      spectrometry.
AB  - Off-line solid-phase extraction (SPE) combined with liquid chromatography
      electrospray tandem mass spectrometry (LC-ESI-MS-MS) was used to study the
      estuarine behaviour of the polar pesticides, atrazine, chloridazon, diuron and
      metolachlor, and their transformation products (TPs), hydroxyatrazine (HA),
      desisopropylatrazine (DIA), desethylatrazine (DEA), 3,4-dichlorophenylmethylurea
      (DPMU) and monuron. The compounds were identified by comparing their LC retention
      times and product-ion spectra with those of standard solutions. In all but one
      case the detection limits of the method were sufficient to determine the
      compounds of interest over the entire salinity range in the estuary. The
      concentrations of the dissolved pesticides ranged from 70 ng l-1 for chloridazon
      to 1350 ng l-1 for diuron. The levels of TPs were 3-8% of the levels of their
      parent pesticide. The mixing plots of polar pesticides and their TPs indicated
      that TPs, which are present in fresh river water, are conservatively transported
      to the sea and that no additional amounts of TPs are formed during their
      transport through the estuary. The one exception was HA, of which approximately
      10% of the amount transported to the North Sea is formed in the lower part of the
      estuary by photochemical oxidation of atrazine. The latter was concluded from the
      ratios of each analyte over the sum total of the parent pesticide and all TPs
      along the salinity gradient, which proved to be a useful tool for identifying
      such estuarine transformations.

PMID- 11296749
TI  - Field cryofocussing hydride generation applied to the simultaneous multi
      elemental determination of alkyl-metal(loid) species in natural waters using ICP
      MS detection.
AB  - Two hydride generation manifold systems, utilizing flow injection and
      cryotrapping techniques for alkyl-metal(loid) speciation analysis in natural
      waters, are described in this paper. They provide shipboard capacity for
      simultaneous derivatization of analytes with NaBH4 and cryotrapping of the
      generated products in a field packed column at -196 degrees C. The first system
      is a large-volume hydride generator, using a reagent-injection flow technique as
      a flow batch type, that has been fully optimized and applied to the simultaneous
      detection of alkylated species in estuarine waters. The technique permits the
      analysis of a large volume sample (0.5-11) at a sampling rate of 3 h-1. The
      second is an online continuous flow hydride generator. A sampling rate of 3-12 h
      1 can be achieved with samples of 0.1-0.51. In addition, shipboard operation
      eliminates major problems related to sample pretreatment, transport and storage.
      Ultra-trace multi-element determination is finally performed in the laboratory by
      cryogenic GC hyphenated with ICP-MS. Routine detection limits of 0.5-10 pg (as
      metal) for 0.51 water samples were achieved for the selected alkyl-metal(loid)
      species of arsenic, germanium, mercury and tin. Concentrations of various
      species, obtained from water samples taken from the Rhine estuary, are also
      presented. These species include alkylated arsenic compounds, other than methyl
      derivatives, that have been tentatively identified and are reported here for the
      first time.

PMID- 11296750
TI  - SI-traceable certification of Cu, Cr, Cd and Pb in sediment and fly ash candidate
      reference materials.
AB  - Many fields in environmental analytical chemistry deal with very low limits and
      thresholds as set by governmental legislations or transnational regulations. The
      need for the accuracy, comparability and traceability of analytical measurements
      in environmental analytical chemistry has significantly increased and total
      uncertainties are even asked for by accreditation bodies of environmental
      laboratories. This paper addresses achieving these goals to guarantee accuracy,
      quality control, quality assurance or validation of a method by means of
      certified reference materials. The assessment of analytical results in certified
      reference materials must be as accurate as possible and every single step has to
      be fully evaluated. This paper presents the SI-traceable certification of Cu, Cr,
      Cd and Pb contents in geological and environmentally relevant matrices (three
      sediments and one fly ash sample). Certification was achieved using isotope
      dilution (ID) ICPMS as a primary method of measurement. In order to reduce
      significantly the number of analytical steps and intermediate samples a multiple
      spiking approach was developed. The full methodology is documented and total
      uncertainty budgets are calculated for all certified values. A non-element
      specific sample digestion process was optimised. All wet chemical digestion
      methods examined resulted in a more or less pronounced amount of precipitate. It
      is demonstrated that these precipitates originate mainly from secondary formation
      of fluorides (essentially CaF2) and that their formation takes place after
      isotopic equilibration. The contribution to the total uncertainty of the final
      values resulting from the formation of such precipitates was in general < 0.1%
      for all investigated elements. Other sources of uncertainty scrutinised included
      the moisture content determination, procedural blank determination, cross
      contamination from the different spike materials, correction for spectral
      interferences, instrumental background and deadtime effects, as well as the use
      of either certified values or IUPAC data in the IDMS equation. The average
      elemental content in the sediment samples was 30-130 micrograms g-1 for Pb, 0.5-3
      micrograms g-1 for Cd and 50-70 micrograms g-1 for Cu. Cr was measured in one
      sample and was about 60 micrograms g-1. The concentrations in the fly ash sample
      were up to 2 orders of magnitude higher. Expanded uncertainty for the
      investigated elements was about 3% (coverae factor k = 2) except for Cr,
      (measured by high resolution ICPMS), for which the expanded uncertainty was about
      7% (k = 2).

PMID- 11296751
TI  - Plants as biomarkers for monitoring heavy metal contaminants on landfill sites
      using sequential extraction and inductively coupled plasma atomic emission
      spectrophotometry (ICP-AES).
AB  - There have been a number of studies investigating metal uptake in plants on
      contaminated landfill sites, but little on their role as biomarkers to identify
      metal mobility for continuous monitoring purposes. Vegetation can be used as a
      biomonitor of site pollution, by identifying the mobilisation of heavy metals and
      by providing an understanding of their bioavailability. Plants selected were the
      common nettle (Uritica Dioica), bramble (Rubus Fruticosa) and sycamore (Acer
      Pseudoplatanus). A study of the soil fractionation was made to investigate the
      soil properties that are likely to influence metal mobility and a correlation
      exercise was undertaken to investigate if variations in concentration of metals
      in vegetation can reflect variations in concentration of the metals in soil. The
      soil was digested using aqua regia in a microwave closed vessel. The vegetation
      was digested using both microwave and a hydrogen peroxide-nitric acid mixture,
      refluxed on a heating block and a comparison made. The certified reference
      materials (CRMs) used were Standard Reference Material (SRM) 1547, peach leaves
      for vegetation (NIST) and for soil CRM 143R, sewage sludge-amended soil (BCR).
      The relative standard deviations (RSDs) were 2-6% for the analyses. Our findings
      show evidence of phytoextraction by some plants, (especially bramble and nettle),
      with certain plants, (sycamore) exhibiting signs of phytostabilisation. The
      evidence suggests that there is a degree of selectivity in metal uptake and
      partitioning within the plant compartments. It was also possible to correlate
      mobility phases of certain metals (Pb, Cu and Zn) using the soil and plant
      record. Zn and Cu exhibited the greatest potential to migrate from the roots to
      the leaves, with Pb found principally in the roots of ground vegetation. Our
      results suggest that analysis of bramble leaves, nettle leaves and roots can be
      used to monitor the mobility of Pb in the soil with nettle, bramble and sycamore
      leaves to monitor Cu and Zn.

PMID- 11296752
TI  - Comparison of BOD results obtained by dilution and manometric methods in sanitary
      landfill leachates.
AB  - This study examined the determination of BOD in landfill leachates by dilution (D
      method) and manometric methods (M-method). The differences in results were
      discussed based on statistical tests. The effects of sample dilution, seeding,
      chloride and total Kjeldahl nitrogen (TKN) level were examined. The M-method was
      found to be more sensitive to increases in chloride and TKN concentrations.
      However, in the M-method the positive interference of nitrogenous BOD (NBOD) to
      carbonaceous BOD (CBOD) was more successfully prevented. The BOD rate constant k
      and the ultimate BOD (BODu) were estimated by non-linear regression. With the M
      method these parameters could be more reliably estimated than the D-method.
      Suggestions were made for BOD analyses in landfill leachates in future studies.

PMID- 11296753
TI  - Influence of solvent and soil type on the pressurised fluid extraction of PAHs.
AB  - Pressurised fluid extraction (PFE) of polycyclic aromatic hydrocarbons (PAHs)
      from a certified reference material (CRM) 524 has been firstly optimised
      following a central composite design. The instrumental parameters of the PFE
      (pressure, temperature, extraction time and number of solvent cycles) were
      studied in order to obtain maximum extraction yields. Neither pressure nor
      extraction time or temperature seemed to have any significant effect on the
      extraction yield, therefore one extraction cycle was enough to exhaustively
      extract all the PAHs from CRM 524. Once the instrumental conditions were
      established, the extraction yields obtained with eight different solvents or
      solvent mixtures [acetone, dichloromethane, acetonitrile, acetone-dichloromethane
      (1 + 1 v/v), acetone-isohexane (1 + 1 v/v), isohexane, methanol and toluene] from
      the CRM 524 were compared and showed that the best recoveries were obtained with
      acetone-isohexane (1 + 1 v/v). Finally, the effect of sand, silt, clay and the
      organic matter content of soil was investigated with respect to recovery of PAHs
      by PFE with different solvents or solvent mixtures for aged soil samples. In this
      case, eight soils with different sand, silt, clay and organic matter contents
      were slurry spiked with PAHs and aged for 19 days. Three aliquots of each slurry
      spiked soil were extracted with the previously mentioned solvents and the results
      were studied by means of principal component analysis (PCA) of the whole data set
      (soil composition, solubility parameter of the solvent and recoveries of all
      PAHs) and partial least squares (PLS). Clay and organic matter content and the
      squared solubility parameter have the highest correlation with the recovery of
      PAHs from soil samples.

PMID- 11296754
TI  - Supercritical fluid extraction of polycyclic aromatic hydrocarbons from white
      pine (Pinus strobus) needles and its implications.
AB  - A supercritical fluid extraction (SFE) method was developed for the extraction of
      polycyclic aromatic hydrocarbons (PAHs) from fresh and fallen pine needles.
      Toluene-modified CO2 was used as the extracting fluid, and the extracted PAHs
      were analyzed by GC-MS. Using a two-stage extraction procedure, a static
      extraction at 180 degrees C and a dynamic extraction at 60 degrees C, and an in
      cell silica gel plug plus a post-oven silica gel column, the extraction and
      fractionation of PAHs can be accomplished in one step. Over a seven month period,
      a significant variation was observed for PAHs in urban samples, while PAHs in
      mountain samples were at much lower levels (by a factor of approximately 8) and
      showed little seasonal change. Although dry fallen needles and fresh needles
      contained similar amounts of PAHs, in the fallen needles the lower molecular
      weight PAHs were partially lost while the higher molecular weight PAHs were
      slightly enriched. Pollution in urban areas was found to be highly localized, and
      buildings and trees are believed to be important factors in the restriction of
      atmospheric PAHs.

PMID- 11296755
TI  - Movement of petroleum hydrocarbons in sandy coastal soils.
AB  - In a field trial, oiled beach sand was buried in a coastal dune system in south
      Wales. A monitoring programme was designed to assess the rate of leaching of
      inorganic ions and hydrocarbons from the deposit. Active breakdown of the
      weathered oil occurred within the oiled beach sand, but hydrocarbons from the
      original material, or arising as a result of degradation, did not follow the same
      leaching pattern as inorganic ions; they remained within the original deposit.
      The results suggest that weathered oil coming ashore from spills at sea can be
      mixed with sand and buried to degrade in coastal soils, without risk of
      groundwater contamination by hydrocarbons.

PMID- 11296756
TI  - Determination of optical parameters for light penetration in particulate
      materials and soils with diffuse reflectance (DR) spectroscopy.
AB  - The results of our investigations of particulate materials (aluminium oxide,
      quartz sand) and "real world" soils (a brown sand and a dark brown soil) using
      diffuse reflectance (DR) spectroscopy are presented. The findings are discussed
      within the framework of Kubelka-Munk (KM) theory as a simplified description of
      light propagation in highly turbid media. The relation between the KM and the
      Lambert-Beer (LB) treatment is outlined. The KM parameters determined were the
      scattering and absorption coefficients (S and K, respectively), and the light
      penetration depths, dp(KM). It was found that in the UV/VIS spectral range the
      scattering coefficients of the materials investigated vary by ca. one order of
      magnitude (S = 6-> 100 cm-1), whereas the absorption coefficients change by more
      than three orders of magnitude (K = < 1-> 1500 cm-1). The different absorption
      and scattering properties of the materials lead to strong variations in light
      penetration depths from the micron into the mm regime [dp(KM) = < 20-> 3500
      microns].

PMID- 11296757
TI  - Preliminary studies of a fast screening method for polycyclic aromatic
      hydrocarbons in soil by using solvent microextraction-gas chromatography.
AB  - Solvent microextraction (SME) was applied to the extraction of polycyclic
      aromatic hydrocarbons (PAHs) from spiked and real environmental soil samples with
      different matrices. Soil sample was mixed with 7 mL of acetone and 14 mL of water
      to allow partitioning of the PAHs from the soil to the liquid phase. A 2 microL
      octane drop suspended from a microsyringe needle tip was then immersed into the
      stirred solution-soil mixture for extraction. After an 11 min extraction, the
      octane drop was withdrawn into the syringe and injected directly into the GC for
      identification and quantification. The whole analysis procedure took 27 min, with
      an extraction time of 11 min, and a GC separation time of 16 min. A second
      extraction could be undertaken whilst the GC is running, hence the GC run time
      currently limits the sample throughput. In this method, a small amount of organic
      solvent was used for the extraction process, which produced little waste. The
      limits of detection for lower molecular weight (< 230) PAHs range from 0.13 to
      0.36 mg kg-1, and for higher molecular weight (> 250) PAHs are estimated to be
      between 0.5 and 1.0 mg kg-1, with RSD values generally under 20%. Due to the
      small volumes of organic solvent used, the consumable cost per extraction is only
      US$ 0.12. This is the first report of the application of SME to solid samples,
      and the first report of the use of SME for the analysis of PAHs.

PMID- 11296758
TI  - Comparison of tanker drivers' occupational exposures before and after the
      installation of a vapour recovery system.
AB  - The purpose of this study was to compare tanker drivers' occupational exposure
      level before and after the installation of vapour recovery facilities at 14
      service stations. Road tanker drivers are exposed when handling volatile petrol
      liquid in bulk in the distribution chain. The drivers' exposure was studied
      during the unloading operation as the bulk petrol flowed into underground storage
      tanks, displacing vapours in the tank space and causing emission to the
      environment and the drivers' work area. The exposures were measured again when
      the dual point Stage I vapour recovery systems were installed for recycling
      vapours. Short-term measurements were carried out in the drivers' breathing zones
      by drawing polluted air through a charcoal tube during unloading. The samples
      were analysed in the laboratory by gas chromatography for C3-C11 aliphatic
      hydrocarbons, tert-butyl methyl ether (MTBE), tert-amyl methyl ether (MTAE),
      benzene, toluene and xylene. The road tanker loads delivered consisted of
      oxygenated and reformulated petrol (E95 and E98 brands), which contained on
      average 13% oxygenates. Before the installation of the vapour recovery system,
      the geometric mean (GM) concentration of aliphatic hydrocarbons was 65 mg m-3
      (range 6-645 mg m-3) in the drivers' breathing zones. After the installation at
      the same service stations, the corresponding exposure level was 8.3 mg m-3 (range
      < 1-79 mg m-3). The GM of the MTBE concentrations was 8.6 mg m-3 (range 1-67 mg m
      3) without vapour recovery and 1.5 mg m-3 (range < 0.1-10 mg m-3) with vapour
      recovery. The differences between the aliphatic hydrocarbons and the MTBE
      exposure levels during the unloading of the road tankers without and with vapour
      recovery were statistically significant (p < 0.05).

PMID- 11296759
TI  - Carbon disulfide at a Chinese viscose factory external and internal exposure
      assessment.
AB  - This article presents the results of carbon disulfide exposure measurements in a
      Chinese viscose rayon factory. The objectives of the study were to identify the
      external exposure levels at a large factory and to investigate the 2
      thiothiazolidine-4-carboxylic acid (TTCA) concentrations in the urine of the
      subjects who were exposed to carbon disulfide in the working place atmosphere.
      The metabolism of carbon disulfide in the exposed subjects was also studied in
      order to demonstrate the best points in time for the internal exposure sampling.
      The measurement of the amount of personal exposure to carbon disulfide in the air
      of the workplace was performed by GC-FPD; the presence of TTCA in the workers
      urine was analyzed by use of a modified HPLC method. The kinetics of TTCA
      excretion was studied by analyses at different time-points both during and after
      exposure to carbon disulfide in the subjects. A total of 155 personal samples
      were obtained. The carbon disulfide concentration in the staple viscose hall was
      13.72 +/- 1.12 mg m-3 in terms of the geometric mean +/- geometric standard
      deviation, and was 20.05 +/- 1.33 mg m-3 in the filament spinning hall. The TTCA
      values in the subjects who worked in the staple spinning hall were 1.18 +/- 0.43
      mg g-1 creatinine and 1.07 +/- 0.38 mg g-1 creatinine for subjects working in the
      filament spinning hall. The best time for TTCA sampling is at the end of the
      working shift, the TTCA excretion was stable for a period of 4-12 h after
      exposure of the subjects to the carbon disulfide. It might be that the Chinese
      have different anthropometric characteristics; a sampling bias may therefore
      appear among different races.

PMID- 11296760
TI  - A ten channel fibre-optic device for distributed sensing of underground
      hydrocarbon leakage.
AB  - With millions of fuel storage tanks and oil pipelines installed around the world,
      there is inevitably frequent leakage of potentially hazardous hydrocarbons. As
      many of these installations are below ground, it can often be many years before
      the extent of the leak is discovered. We have previously reported the development
      of a sensor for the detection of such subterranean leaks, using infrared
      reflectometry to interrogate a hydrocarbon sensitive membrane. However, a single
      sensor cannot provide any information about the flow rate or direction of the
      leak. This paper describes the extension of the technology to a multi-channel
      distributed sensing system, using optical fibres capable of distributing the
      sensors over large subterranean areas. Results are reported from the evaluation
      of the device, which consisted of monitoring the movement of different
      hydrocarbons (gasoline, diesel and insulating oil) through a vertical sand-filled
      vessel.

PMID- 11296761
TI  - What future for dioxins?

PMID- 11296763
TI  - Major EU legislation finalised.

PMID- 11296762
TI  - Canada and US finalise ozone agreement.

PMID- 11296764
TI  - EU tackles new water law.

PMID- 11296765
TI  - US introduces consolidated regs.

PMID- 11296766
TI  - New options needed for transport emissions.

PMID- 11296768
TI  - Living with the greenhouse effect.

PMID- 11296767
TI  - North American pollution controls take effect.

PMID- 11296769
TI  - Indicators show mixed results for the Great Lakes.

PMID- 11296770
TI  - UK water quality: could do better.

PMID- 11296771
TI  - EU divided over phthalate leaching tests.

PMID- 11296772
TI  - Scientists criticise EDC list.

PMID- 11296773
TI  - Regulators close in on wood chemicals.

PMID- 11296774
TI  - Study demonstrates phthalate exposure.

PMID- 11296775
TI  - Advances in EDC testing.

PMID- 11296776
TI  - Arctic nations to assess climate change.

PMID- 11296777
TI  - European networks reviewed.

PMID- 11296778
TI  - Monitoring of platinum in the environment.
AB  - Since the introduction of catalytic converters for the control of vehicle
      emission, a controversial discussion has begun on platinum emission and its
      eventual consequences for the environment. This brief overview covers the main
      aspects of anthropogenic emission of platinum and its bioavailability. Modern
      analytical methods for Pt determination in different environmental samples are
      also presented.

PMID- 11296779
TI  - Elder abuse: under-recognised and under-reported.

PMID- 11296780
TI  - The pattern of elderly abuse presenting to an emergency department.
AB  - AIM: To determine the pattern and frequency of elder abuse presenting to an urban
      Emergency unit in Singapore. METHOD: The survey was conducted from May 1994 to
      December 1997. The patients consisted of adults who were 65 years or older who
      presented to the Emergency Department with non-accidental trauma or complained of
      other acts of cruelty. RESULT: 17 cases of elder abuse were found, out of a total
      of 62,826 elderly patients. The frequency of elder abuse presenting to the
      Emergency Department was 0.03%. Elder abuse makes up 2.9% of all cases of family
      violence involving adults in this period. The average age was 74.6 years old.
      There was a predominance of Chinese females. In 58.8% the assailants were the
      daughter-in-law or son. 70.5% were ambulatory. Most (76.4%) had a chronic medical
      illness, commonly hypertension, diabetes mellitus, or both. Blunt musculoskeletal
      trauma, head or maxillofacial injuries were the commonest injuries encountered.
      CONCLUSION: Elder abuse is a significant subset of Family Violence. It may be
      more widespread than thought. Awareness of its occurrence is a first step in
      halting its progression.

PMID- 11296781
TI  - Technical aspect of ThinPrep.
AB  - AIM OF STUDY: To analyze the common technical problems encountered in ThinPrep
      preparations. METHOD: A prospective and retrospective study of eight hundred and
      fifty (n = 850) conventional cervical smears with its corresponding paired
      ThinPrep specimens from July 1998 to December 1998. RESULTS: 139 ThinPreps were
      found to be technically suboptimal. Of these, 81 showed "patchy cells lost"; 18
      showed "thick preparations"; 24 demonstrated "halo effect'" where the cellular
      material collected at the periphery of the cell circle, and 16 had "obscuring
      blood and amorphous debris", rendering the preparations "satisfactory for
      evaluation but limited" by the presence of the above artifacts. CONCLUSION:
      Despite its many advantages in providing standardization of specimen preparation,
      superb cellular presentation, reduction in the number of unsatisfactory reports
      and increased lesion detection rate, ThinPrep has its own limitations in terms of
      technical problems, ease of operation and cost effectiveness.

PMID- 11296782
TI  - Asthma in the elderly--a more severe disease.
AB  - OBJECTIVE: To determine the severity of asthma in the elderly compared to the
      younger asthmatics. DESIGN: Cross-sectional study. SETTING: University outpatient
      asthma clinic. SUBJECTS: Asthmatics seen over a 6 month period in 1997. RESULTS:
      There were 154 patients and 16% were elderly (> 65 years) asthmatics. The elderly
      asthmatics were on significantly more anti-asthmatic medications (2.3 +/- 1.1 vs.
      1.6 +/- 0.9, p < 0.001), and their clinical severity was significantly worse than
      their younger counterparts (Step 2.2 +/- 1.2 vs. 1.7 +/- 1.0, p < 0.001). Near
      fatal asthma episodes were also more common in the elderly asthmatics (39% vs
      13%, chi 2 test p < 0.01). CONCLUSIONS: Elderly asthmatics appear to have more
      severe asthma as evidenced by the increase in near-fatal episodes, and their
      increased clinical severity.

PMID- 11296783
TI  - Social impact of nasopharyngeal carcinoma on Chinese households in Selangor,
      Malaysia.
AB  - AIM OF STUDY: With a five-year survival rate of 20% in 1970 and 40-45% in 1990,
      and highest incidence and mortality in early and middle adult years,
      nasopharyngeal carcinoma (NPC) may have a severe social impact on families and
      households. The aim of this study was to measure the social impact of NPC in the
      Chinese population of Selangor, Malaysia. METHOD: Cases were pooled from three
      epidemiological case-control studies conducted in 1973-74, 1980, and 1990-92 for
      a total of 442. They lived in households with a grand total of 2,598 persons.
      Interviewers collected data on household composition: number of residents; each
      resident's age, sex, occupation, and relationship to the head of the household;
      and position of the NPC case in the household. RESULTS: Ninety-four percent of
      cases supported 93% of household members in some way. Most cases were employed as
      income earners or homemakers and 80% had a key role as head of household and/or
      parent of dependent children. CONCLUSION: The illness and death caused by NPC had
      a major social impact on immediate families and on extended family and non-kin
      households as well.

PMID- 11296784
TI  - A stair-climb test of cardiorespiratory fitness for Singapore.
AB  - OBJECTIVE: The purpose of this study was to develop a stair-climb test of
      cardiorespiratory fitness for adult Singaporeans, particularly those staying in
      Singapore Housing and Development Board (HDB) flats. METHOD: 103 subjects [56
      males, of mean (SD) age 44.8 (13.9) years and Body Mass Index, or BMI, 23.3
      (3.2); and 47 females, of age 43.2 (12.9) years and BMI 21.9 (2.8)] were first
      assessed for their cardiorespiratory fitness, measured using maximal oxygen
      uptake (or VO2max) on a treadmill, before undergoing a stair-climb test up to the
      12th storey (11 floors) of a typical HDB flat (180 steps, vertical height 27.0
      metres). RESULTS: The mean (SD) time taken for the climb (CT) and heart rate at
      the end of the climb (HRend) averaged 111.3 (16) seconds and 154.4 (13.4)
      beats.min-1 respectively for males, and 121.0 (18.1) seconds and 164.6 (15.7)
      beats.min-1 respectively for females. Regression equations were developed to
      predict VO2max from age (years), BMI, CT (seconds), HRend (beats.min-1): For
      males: VO2max (ml.kg-1.min-1) = 133 - 0.273 (Age) - 0.672 (BMI) - 0.236 (CT) -
      0.232 (HRend). For females: VO2max (ml.kg-1.min-1) = 66.69 - 0.135 (Age) - 0.249
      (BMI) - 0.128 (CT) - 0.021 (HRend). Validation of the regression equations
      conducted on a different sample consisting of 18 subjects (11 male and 7 female)
      showed significant correlations between the predicted and directly measured
      VO2max (males, r = 0.81 and females, r = 0.90; p < 0.01). There were no
      significant differences between the means of predicted and directly measured
      VO2max. CONCLUSION: A stair-climb test using HDB stairs was developed which was
      able to estimate cardiorespiratory fitness with reasonable accuracy.

PMID- 11296785
TI  - BCR-ABL positive essential thrombocythaemia: a variant of chronic myelogerous
      leukaemia or a distinct clinical entity: a special case report.
AB  - A 37-year-old Malay man presented initially with the clinical picture of
      essential thrombocythaemia (ET) without the extreme leukocytosis, marked
      splenomegaly and low neutrophil alkaline phosphatase characteristic of chronic
      myelogenous leukaemia (CML). Bone marrow examination showed massive
      megakaryocytic hyperplasia; cytogenetic studies showed the presence of
      Philadelphia chromosome. The patient was treated with hydroxyurea that resulted
      in reduction in the platelet count. Seventeen months later, he presented with
      fever associated with tender massive splenomegaly. Bone marrow finding was
      consistent with chronic phase CML. The presence of a rearrangement involving the
      major breakpoint cluster region (M-bcr) on chromosome 22 was confirmed by reverse
      transcriptase-polymerase chain reaction. The clinical importance of finding the
      Philadelphia chromosome in patients who seem to have ET is in assessing
      prognosis. ET generally follows a chronic, indolent course. However, this patient
      who had Philadelphia chromosome underwent clinical transition to chronic phase
      CML17 months and blast crisis 29 months after presentation.

PMID- 11296786
TI  - Delayed diagnosis of cervical pregnancy: management options.
AB  - Cervical pregnancy is an uncommon variety of ectopic gestation. The aetiology is
      obscure. Diagnosis can be missed unless early evaluation is done by experienced
      personnel utilising pelvic ultrasonography. Three cases of cervical pregnancy
      managed at this hospital are described illustrating difficulties in early
      diagnosis and possible association with previous uterine scar and prior curettage
      of the uterus for retained products of conception. Treatment options vary
      according to the clinical state of the patient at the time of diagnosis. Non
      surgical methods including systemic methotrexate administration in one and
      surgical evacuation of products of conception with subsequent cervical cerclage
      in another are discussed. Surgical interventions like total abdominal
      hysterectomy with internal iliac artery ligation to arrest life-threatening
      pelvic haemorrhage is also described. Other treatment options include potassium
      chloride (KCl) alone or in combination with methotrexate.

PMID- 11296787
TI  - Acute retinal necrosis syndrome complicating chickenpox.
AB  - Chickenpox may be complicated by ocular involvement. In these patents, acute
      retinal necrosis usually forms a relatively mild course. Systemic antiviral
      treatment during the acute phase of the disease is recommended. Rarely, retinal
      detachment may develop, resulting in blindness. It is strongly recommended that
      patients with chickenpox who develop visual symptoms should be referred for an
      ophthalmological opinion early.

PMID- 11296788
TI  - Cortical blindness following coronary angiography.
AB  - A 53-year-old man developed transient cortical blindness after coronary
      angiography, which appears to be an adverse reaction to contrast agent. A
      possible mechanism of this complication is contrast penetration of the blood
      brain barrier with direct neurotoxicity to the occipital cortex.

PMID- 11296789
TI  - Concepts in acute coronary syndromes.
AB  - Landmark pathological studies have deepened our understanding of the mechanisms
      behind acute coronary syndromes over the last decade. Thrombosis plays a key role
      and is a unifying feature in the pathogenesis. Platelet-rich thrombus
      superimposed over the disrupted atherosclerotic plaque or eroded plaque
      endothelium, with or without fibrin-thrombus extension, is evident in postmortem
      necropsy, angiographic and angioscopic studies. However features which contribute
      to the risk of acute events lie in the atherosclerotic plaque itself. Plaque
      content and not plaque size is the important factor. A vulnerable plaque may be
      invisible on clinical stress testing and even coronary angiography; but it is
      prone to rupture if it has only a thin cap and a proportionally larger lipid
      core. There is a cellular preponderance of activated macrophages and T
      lymphocytes; and high activity of matrix metalloproteinases in vulnerable
      plaques. Smooth muscle cell proliferation and collagen synthesis are
      downregulated. These features may serve as possible targets for detecting plaques
      at risk or for reversing the risk of vulnerable plaques.

PMID- 11296790
TI  - Clinics in diagnostic imaging (56). Cavernous vascular malformation with
      intracerebral haematoma.
AB  - A 28-year-old woman presented following a seizure. Physical and neurological
      examinations showed no significant abnormality except a drowsy mental state.
      Routine laboratory studies were normal. Emergency MR imaging showed a rounded,
      high signal intensity lesion with a focal eccentric heterogeneous signal focus in
      the right frontal lobe. The heterogeneous focus revealed an irregular low signal
      rim on T1- and T2-weighted images. Mild surrounding parenchymal oedema was noted.
      The eccentric focus showed some central enhancement. The diagnosis of cavernous
      vascular malformation with intracerebral haematoma was confirmed at surgery. The
      combination of typical MR imaging findings, with clinical and family histories
      consistent with cavernous angiomata provides sufficient conclusive evidence.

PMID- 11296791
TI  - Proceedings of the International Symposium on Fertilization and Development of
      Sea Urchin and Marine Invertebrates. December 9-11, 1999. Tokyo, Japan.

PMID- 11296792
TI  - Response to "family therapy saves the planet".

PMID- 11296793
TI  - The shifting HIV/AIDS paradigm: twenty years and counting.

PMID- 11296794
TI  - Rhabdomyolysis caused by electric injury.

PMID- 11296795
TI  - Proceedings of the 6th Meeting of the European Society of Sonochemistry. Rostock
      Warnemunde, Germany, 10-14 May 1998.

PMID- 11296796
TI  - The Hubert de Watteville Memorial Lecture. Imagine a world where motherhood is
      safe for all women--you can help make it happen.
AB  - The neglected tragedy of maternal mortality is a health scandal of our time.
      Motherhood can be made safe for all women and obstetricians have a global social
      responsibility to make it happen. Ten propositions are outlined: safe motherhood
      is to be recognized as a woman's human right; a woman's life is to be considered
      worth saving; life-saving emergency obstetric care is to made accessible to all
      women when they need it; all deliveries are to be attended by skilled birth
      attendants; all pregnant women are to have access to prenatal care; motherhood
      must be a voluntary woman's choice; making motherhood safe for all women is to be
      an international commitment; lack of resources in developing countries is not to
      be accepted as an excuse for inaction; women, North and South should mobilize for
      women's right to life; and our profession should act without national frontiers.
      The challenge is great, but so also is the reward.

PMID- 11296797
TI  - ACOG practice bulletin: management of anovulatory bleeding.

PMID- 11296798
TI  - Management of spontaneous pneumothorax.

PMID- 11296799
TI  - Foreign bodies in the nasal cavities: a comprehensive review of the aetiology,
      diagnostic pointers, and therapeutic measures.

PMID- 11296800
TI  - Eosinophilic pericarditis caused by minocycline.

PMID- 11296801
TI  - Bibliography. Current world literature. Erythrocytes.

PMID- 11296803
TI  - Exercise combined with continuous passive motion or slider board therapy compared
      with exercise only: a randomized controlled trial of patients following total
      knee arthroplasty.
AB  - BACKGROUND AND PURPOSE: The primary purpose of this randomized controlled trial
      was to determine which method of mobilization - (1) standardized exercises (SE)
      and continuous passive motion (CPM), (2) SE and slider board (SB) therapy, using
      an inexpensive, nontechnical device that requires minimal knee active range of
      motion (ROM), or (3) SE alone-achieved the maximum degree of knee ROM in the
      fIrst 6 months following primary total knee arthroplasty (TKA). The secondary
      purpose was to compare health-related quality of life among these 3 groups.
      SUBJECTS: The subjects were 120 patients (n=40/group) who received a TEA at a
      teaching hospital between June 1997 and July 1998 and who agreed to participate
      in the study. METHODS: Subjects were examined preoperatively, at discharge, and
      at 3 and 6 months after surgery. The examination consisted of measurement of knee
      ROM and completion of the Western Ontario and McMaster Universities (WOMAC)
      Osteoarthritis Index and the Medical Outcomes Study 36-Item Short-Form Health
      Survey (SF-36). RESULTS: The 3 treatment groups were similar with respect to age,
      sex, and diagnosis at the start of the study. There were no differences in knee
      ROM or in WOMAC Osteoarthritis Index or SF-36 scores at any of the measurement
      intervals. The rate of postoperative complications also was not different among
      the groups. DISCUSSION AND CONCLUSION: When postoperative rehabilitation regimens
      that focus on early mobilization of the patient are used, adjunct ROM therapies
      (CPM and SB) that are added to daily SE sessions are not required. Six months
      after TEA, patients attain a satisfactory level of knee ROM and function.

PMID- 11296802
TI  - Are patients truthful about their smoking habits? A validation of self-report
      about smoking cessation with biochemical markers of smoking activity amongst
      patients with ischaemic heart disease.
AB  - AIMS: To validate self-report about smoking cessation with biochemical markers of
      smoking activity amongst patients with ischaemic heart disease. PATIENTS AND
      METHODS: Outpatients at the Division of Cardiology, 75 years of age or younger,
      who had been Hospitalized at Sahlgrenska University Hospital in Goteborg due to
      an ischaemic event and who consecutively participated in a nurse-monitored
      routine care programme for secondary prevention, from 6 February 1997 to 5
      February 1998. Data concerning smoking habits were collected through interviews.
      Two chemical markers, cotinine in plasma and carbon monoxide (CO) in expired air,
      validated self-reports concerning smoking cessation. RESULTS: 260 former smokers
      were validated. In the vast majority of the study population, the anamnestic
      information concurred with the chemical marker. However, 17 patients had chemical
      markers that contradicted their self-report with raised CO (n = 6) and/or raised
      cotinine levels (n = 13) without alternative nicotine delivery. CONCLUSION: Most
      patients with coronary artery disease relating information concerning cessation
      of smoking are truthful. A few patients, however, seem to conceal their smoking.
      Testing by chemical markers may be questionable for ordinary care but should,
      however, be included in studies concerning the association between smoking and
      health.

PMID- 11296804
TI  - Staging of gynecologic malignancies.
AB  - Magnetic resonance imaging (MRI) is gaining momentum for staging gynecologic
      malignancies. MRI staging is an adjunct to clinical and surgical staging in women
      with cervical or endometrial cancer, respectively. For women with possible
      adnexal pathology, MRI is useful for lesion characterization. In patients with
      ovarian cancer, MRI determination of disease extent helps treatment planning,
      either as a surgical roadmap or to identify nonresectable patients.

PMID- 11296805
TI  - Magnetic resonance imaging of the ovary.
AB  - Magnetic resonance imaging (MRI) of the pelvis can characterize a wide variety of
      ovarian lesions. We discuss MRI strategies for identification and
      characterization of ovarian neoplasms and correlate MRI findings with lesion
      gross pathological and histopathological structure.

PMID- 11296806
TI  - Magnetic resonance imaging of the perineum and pelvic floor.
AB  - The aim of this article is to review the magnetic resonance (MR) findings of
      pelvic floor descent and pelvic organ prolapse in women. In addition, a detailed
      grading system of pelvic organ prolapse and pelvic floor relaxation based on
      dynamic MR imaging is presented. The technique described here uses very fast MR
      sequences, is reproducible and easily learned by radiologists and technologists,
      is well accepted by patients, and provides as much information as traditional
      projectional X-ray imaging. Reference points are the pubococcygeal line and
      puborectalis muscle sling. The grading system is based on degree of organ
      prolapse through the hiatus and the degree of puborectalis descent and hiatal
      enlargement.

PMID- 11296808
TI  - Electromyographic studies of structural abnormalities. 1941.

PMID- 11296807
TI  - Fetal magnetic resonance imaging.
AB  - Ultrafast magnetic resonance imaging (MRI) sequences have changed the use of MRI
      to evaluate fetal abnormalities. Currently, the best application is the
      evaluation of suspected brain abnormalities found on ultrasound. MRI
      differentiates the various types of fetal ventriculomegaly. Superior posterior
      fossa visualization allows differentiation of Dandy-Walker malformation from a
      large cisterna magna. Anomalies of the corpus callosum can be seen. MRI also is
      valuable in the evaluation of fetal giant neck masses for planning delivery of
      the baby and surgery for life-threatening airway obstruction. In the chest, MRI
      differentiates masses such as diaphragmatic hernia, cystic adenomatoid
      malformation, and sequestration, and it aids in planning fetal surgery because
      MRI directly visualizes the position of the lung, liver, and bowel.

PMID- 11296809
TI  - Muscle and the myoneural junction. Their relation to segmental spinal
      dysfunctions. 1955.

PMID- 11296810
TI  - Analyzing the osteopathic lesion. 1940.

PMID- 11296811
TI  - Hypothalamic-pituitary-thyroidal axis dysfunction and cortisol secretion in
      patients with nonclassical congenital adrenal hyperplasia.
AB  - OBJECTIVE: The purpose of this study was to evaluate thyroid function and TSH and
      cortisol (F) secretion in hyperandrogenemic women with nonclassical congenital
      adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (Group A) when
      compared with women with hyperandrogenemic symptoms (menstrual irregularities,
      hirsutism, acne, seborrhea and sterility) of other etiologies (Group B). METHODS:
      Seventy-two women were subjected to stimulation of the adrenal cortex with i.v.
      ACTH administration in the early proliferative phase of the menstrual cycle.
      Basal plasma TSH, T3, T4, and FTI as well as basal and ACTH-stimulated plasma F
      and 17-hydroxyprogesterone levels were determined. RESULTS: According to
      internationally accepted criteria and HLA haplotyping, we diagnosed 28 NC-CAH
      patients as well as affected heterozygotes of the disease. No significant
      difference was found in the plasma T3, T4, or FTI or F concentrations between the
      women of the two groups. On the contrary, plasma TSH levels were significantly
      lower in patients with 21-hydroxylase deficiency when compared to the women with
      hyperandrogenemic symptoms of other etiologies. CONCLUSION: The results of this
      study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to
      altered ACTH secretion patterns.

PMID- 11296812
TI  - Recommendation to standardize pediculicidal and ovicidal testing for head lice
      (Anoplura: Pediculidae).
AB  - Pediculosis capitis is a prevalent and highly communicable condition infesting
      millions of elementary school students annually. Topical insecticides are the
      present standard treatment for this condition. Because resistance of head lice to
      insecticides is a growing concern, assessment of efficacy of pediculicidal and
      ovicidal activity of the various agents is needed for public health interests.
      Given the number of anecdotal and market-driven reported studies, assessment of
      topical lice therapies requires standardized testing. Evaluations based on
      adaptations of World Health Organization guidelines are not ideal, whereas a
      protocol reflecting clinical exposure to insecticides is preferable.

PMID- 11296813
TI  - Vector competence of North American mosquitoes (Diptera: Culicidae) for West Nile
      virus.
AB  - We evaluated the potential for several North American mosquito species to
      transmit the newly introduced West Nile (WN) virus. Mosquitoes collected in the
      New York City metropolitan area during the recent WN virus outbreak, at the
      Assateague Island Wildlife Refuge, VA, or from established colonies were allowed
      to feed on chickens infected with WN virus isolated from a crow that died during
      the 1999 outbreak. These mosquitoes were tested approximately 2 wk later to
      determine infection, dissemination, and transmission rates. Aedes albopictus
      (Skuse), Aedes atropalpus (Coquillett), and Aedes japonicus (Theobald) were
      highly susceptible to infection, and nearly all individuals with a disseminated
      infection transmitted virus by bite. Culex pipiens L. and Aedes sollicitans
      (Walker) were moderately susceptible. In contrast, Aedes vexans (Meigen), Aedes
      aegypti (L.), and Aedes taeniorhynchus (Wiedemann) were relatively refractory to
      infection, but individual mosquitoes inoculated with WN virus did transmit virus
      by bite. Infected female Cx. pipiens transmitted WN virus to one of 1,618 F1
      progeny, indicating the potential for vertical transmission of this virus. In
      addition to laboratory vector competence, host-feeding preferences, relative
      abundance, and season of activity also determine the role that these species
      could play in transmitting WN virus.

PMID- 11296814
TI  - Aedes (Finlaya) japonicus (Diptera: Culicidae), a newly recognized mosquito in
      the United States: analyses of genetic variation in the United States and
      putative source populations.
AB  - Introduction of potential disease vectors into a new geographic area poses health
      risks to local human, livestock, and wildlife populations. It is therefore
      important to gain understanding of the dynamics of these invasions, in particular
      its sources, modes of spread after the introduction, and vectorial potential. We
      studied the population genetics of Aedes (Finlaya) japonicus japonicus
      (Theobald), an Asian mosquito that was recognized for the first time in the
      United States in 1998. We examined patterns of genetic diversity using random
      amplified polymorphic DNA and sequences of ND4 of mtDNA by comparing samples from
      populations spanning the range of this mosquito in Japan (six samples) and the
      United States (nine samples) as well as specimens intercepted in New Zealand in
      1999. We found geographically differentiated populations in Japan, indicating
      limited gene flow even on small spatial scales. In the United States, we found
      evidence of significant genetic differentiation between samples from New York,
      Connecticut, and New Jersey and those from mid-Pennsylvania and Maryland. We were
      unable to pinpoint the source location(s) in Japan, although some of the U.S.
      samples are genetically close to samples from south Honshu and western Kyushu.
      Further studies should include samples from Korean populations. Distinct genetic
      signatures in U.S. populations undergoing expansion suggest the possibility of
      local increases in genetic diversity if and where they meet.

PMID- 11296816
TI  - A new species of the genus periglischrus (Acari: Mesostigmata: Spinturnicidae) on
      Choeronycteris mexicana (Chiroptera: Phyllostomidae) in Central Mexico.
AB  - Periglischrus leptosternus new species was found on the bat Choeronycteris
      mexicana in the central part of Mexico. The female, male, and protonymph are
      described and illustrated.

PMID- 11296815
TI  - A simple method to identify triatomine (Hemiptera: Reduviidae) feces in sensing
      devices used in vector surveillance programs.
AB  - We successfully applied the phenolphthalin (Kastle-Meyer) test used in forensic
      chemistry to distinguish between feces from triatomines and other domestic
      arthropods in sensing devices used for vector surveillance. All black or dark
      brown, but not white or yellow, fecal smears from laboratory-reared or field
      collected Triatoma infestans Klug, Triatoma guasayana Wydgozinsky & Abalos,
      Triatoma sordida Stahl (recently revalidated as Triatoma garciabesi Carcavallo,
      Cichero, Martinez, Prosen & Ronderos) tested positive, whereas dejecta from
      cockroaches and spiders, crickets, beetles, predatory bugs, and domestic flies
      tested negative. Black or dark brown dejecta from female Aedes aegypti L. and
      Cimex lectularius L. bedbugs also tested positive. In sellsing devices installed
      in bedrooms of 11 houses in Amama, rural northwestern Argentina, where neither
      cimicid bedbugs nor argasid ticks had been found over the years, only 62% of the
      black or dark brown fecal smears attributed to triatomines by a skilled observer
      tested phenolphthalin-positive. After insecticidal spraying, when bedroom areas
      were not colonized by triatomines, only 33-40% of the black or dark brown fecal
      smears in sensor boxes attributed to triatomines by another skilled observer
      tested phenolphthalin-positive. Eleven (79%) ofthe 14 houses with dubious or
      nontypical triatomine feces tested phenolphthalin-positive at least once during
      1993-1995. Our study introduces a low-cost, simple and effective procedure for
      the identification of triatomine feces. The test, as a helpful adjunct to sensing
      devices used in triatomine surveillance, will aid in the accurate detection of
      infestations and the determination of the need for insecticide application.

PMID- 11296817
TI  - Destruction of bacteria in the digestive tract of the maggot of Lucilia sericata
      (Diptera: Calliphoridae).
AB  - Green fluorescent protein-producing Escherichia coli were used to investigate the
      fate of bacteria in the alimentary tract of sterile grown maggots, Lucilia
      sericata (Meigen), using a laser scanning confocal microscope. A computer program
      was used to analyze the intensity of the fluorescence and to quantify the number
      of bacteria. The crop and the anterior midgut were the most heavily infected
      areas of the intestine. A significant decrease in the amount of bacteria was
      observed in the posterior midgut. The number of bacteria decreased even more
      significantly in the anterior hindgut and practically no bacteria were seen in
      the posterior end, near the anus. The viability of bacteria in the different gut
      sections was examined. It was shown that 66.7% of the crops, 52.8% of the
      midguts, 55.6% of the anterior hindguts, and 17.8% of posterior hindguts harbored
      living bacteria. In conclusion, during their passage through the digestive tract
      the majority of E. coli was destroyed in the midgut. Most of the remaining
      bacteria were killed in the hindgut, indicating that the feces were either
      sterile or contained only small numbers of bacteria.

PMID- 11296818
TI  - Infection of Ixodes scapularis (Acari: Ixodidae) with Borrelia burgdorferi using
      a new artificial feeding technique.
AB  - To study interactions between Ixodes scapularis (Say) and Borrelia burgdorferi,
      an artificial feeding system was refined to allow controlled manipulation of
      single variables. The feeding system uses a mouse skin mounted on a water
      jacketed glass membrane feeder. I. scapularis were infected using either BSK-H
      cultured B. burgdorferi spirochetes or a B. burgdorferi-infected mouse skin as
      the source of spirochetes. Sixty-six percent of nymphs successfully fed to
      repletion using the artificial feeding systems with at least 75% of nymphs
      becoming infected with B. burgdorferi. Strain B31 B. burgdorferi spirochetes from
      passages 2-17 were equally infectious to nymphal ticks. At concentrations of one
      spirochete per microliter, 12% of nymphs acquired infection and 14 and 100
      spirochetes per microliter resulted in 50 and 100% infection rates, respectively.
      Eighty-nine percent of nymphs fed by artificial feeding molted to the adult
      stage. When subsequently fed as adults, these I. scapularis successfully
      transmitted infectious B. burgdorferi spirochetes to mice.

PMID- 11296819
TI  - Evaluation of Beauveria bassiana (hyphomycetes) strains as potential agents for
      control of Triatoma infestans (Hemiptera: Reduviidae).
AB  - Chagas disease constitutes a major human health problem in most Latin American
      countries. This endemic disease is transmitted by several species of triatomine
      bugs, the most important being Triatoma infestans (Klug). In this article, we
      report on the selection of strains of the entomopathogenic fungus Beauveria
      bassiana (Bals.) Vuill. virulent to T. infestans for possible use as
      bioinsecticides. Four strains of B. hassiana isolated from Argentina (Bb 1, 10,
      25, and 65) were evaluated. To calculate mortality and mean lethal time, nymphs
      and adults of T. infestans were treated with conidia produced on complete agar
      medium and wheat brain and rice husk medium (WH). The LD50 for nymphs and adults
      of T. infestans was calculated. The effect of different temperatures (18, 22, 26,
      30, and 34 degrees C) and relative humidities (35 and 90% RH) on mortality of
      nymphs were studied. We evaluated the compatibility of strains with Deltamethrin
      and Beta-Cypermethrin. Although the strain Bb 25 failed to grow on WH, the other
      three strains showed similar mortality values independent of the culture medium
      used to grow the microorganisms. The lowest LD50 values for nymphs were obtained
      with the strains Bb 10 and 65 and for adults were Bb 1, 10, and 65. The highest
      mean mortality was obtained with strain Bb 10, and among temperatures the highest
      mean mortality was observed at 26 degrees C. Relative humidity did not affect the
      mortality of T. infestans nymphs with all strains and temperatures assayed.
      Deltamethrin did not affect any of the three strains for the four studied doses,
      and Beta-Cypermethrin could be used in combination with the fungus only at low
      doses. The strain Bb 10 was selected for future assays under natural climatic
      conditions.

PMID- 11296820
TI  - Growth and survival of immature Heamatobia irritans (Diptera; Muscidae) is
      influenced by bacterial isolated from cattle manure and conspecific larvae.
AB  - Twenty species of bacteria were isolated from cattle manure and seven species
      were isolated from the gut of larval horn fly Hematobia irritans (L.). Bacteria
      in manure belonged to the Bacillaceae, Pseudomonadaceae, Micrococcaceae,
      Corynebacteriaceae, Enterobacteriaceae, Microbacteriaceae, and two unassigned
      genera. Gut bacteria belonged to the Enterobacteriaceae, Bacillaceae,
      Neisseriaceae, and Pseudomonadaceae. H. irritans larval survival and growth on
      the various bacterial species were evaluated by rearing larvae in sterilized
      cattle manure that was inoculated with single bacterial isolates. H. irritans
      larvae failed to develop in sterilized, uninoculated manure, indicating that
      bacteria are necessary for larval development. Survival averaged 74% in
      nonsterilized manure and ranged from 4 to 53% in manure with individual isolates.
      Survival was highest when larvae were reared on manure inoculated with
      Pseudomonadaceae, Corynebacteriaceae, Micrococcaceae, and Bacillaceae and was
      lowest when reared in manure inoculated with Enterobacteriaceae and
      Microbacteriaceae. Pupal weights were heaviest when reared on the Flavobacteria,
      followed by the Pseudomonadaceae and Corynebacteriaceae. Pupae averaged 4.9 +/-
      0.08 mg when reared on gram-negative isolates, compared with 3.6 +/- 0.09 mg when
      reared on gram-positive isolates. Pupal weights were not significantly correlated
      with larval survival, indicating that bacteria that promote growth do not
      necessarily promote survival. A reproductive index was used as a measure of
      fitness and was highest for larvae reared in the nonsterile control, followed
      most closely by Pseudomonadaceae and Corynebacteriaceae. These groups appeared to
      best meet the nutritional requirements of larvae and may be used in further
      experiments to define an artificial rearing media for H. irritans.

PMID- 11296821
TI  - Selective oviposition by Aedes aegypti (Diptera: culicidae) in response to
      Mesocyclops longisetus (Copepoda: Cyclopoidea) under laboratory and field
      conditions.
AB  - The influence of predacious Mesocyclops longisetus Thiebaud on the selection of
      oviposition sites by prey Aedes aegypti (L.) was studied under laboratory and
      field conditions. In both cases, gravid Ae. aegypti females were significantly
      more attracted to ovitraps containing copepods or to ovitraps with water in which
      copepods were held previously than to distilled water. Monoterpene and
      sesquiterpene compounds including 3-carene, alpha-terpinene, alpha-copaene, alpha
      longipinene, alpha-cedrene, and delta-cadinene were found in hexane extracts of
      copepods by gas chromatography and mass spectrometry analyses. These compounds
      may be responsible for attracting gravid Ae. aegypti females and may increase the
      number of potential prey for the copepod.

PMID- 11296822
TI  - Topical application as a method for comparing  the effectiveness of insecticides
      against cat flea (Siphonaptera: Pulicidae).
AB  - A topical (micro-droplet) bioassay is described for the cat flea, Ctenocephalides
      felis (Bouche). Key parameters are the short carbon dioxide anesthetization and
      the use of 0.1 ml of acetone per flea. The method was used to compare the
      effectiveness of 13 insecticides. LD95 values in nanograms per flea were
      nitenpyram 0.68, fipronil 0.69, deltamethrin 0.70, imidacloprid 0.81,
      cypermethrin 5.4, fenthion 8.0, diazinon 12, permethrin 19, malathion 29,
      bendiocarb 170, DDT 710, propoxur 1,300, carbaryl >10,000. Experiments repeated 2
      5 yr later, with five of the chemicals, in a different facility, showed only
      small shifts in potency (0.38- to twofold of the original LD50 values).

PMID- 11296823
TI  - Seasonal transmission of bluetongue virus by Culicoides sonorensis (Diptera:
      Ceratopogonidae) at a southern California dairy and evaluation of vectorial
      capacity as a predictor of bluetongue virus transmission.
AB  - Vectorial capacity of Culicoides sonorensis Wirth & Jones for the transmission of
      bluetongue (BLU) virus was examined at a southern California dairy from January
      1995 to December 1997. Insects were collected one to two times per week in five
      CDC-type suction traps (without light) baited with CO2 at a constant release rate
      of 1,000 ml/min. BLU virus was detected in midges collected from May through
      December with an estimated overall infection rate of 0.08%. The BLU virus
      infection rate of field-captured midges was not correlated with sentinel calf
      seroconversions to BLU virus. Sentinel calf seroconversions were highly seasonal,
      occurring from August through November with most calves seroconverting during
      September and October. Vector competence of field-collected nulliparous flies fed
      a locally acquired serotype of BLU virus in the laboratory was stable among years
      (17-23%). Vectorial capacity was strongly correlated with BLU virus transmission
      (measured by sentinel calf seroconversions) during 1995 and 1996, but not during
      1997. Host biting rate estimated for traps nearest to the sentinel calves was the
      index best correlated with BLU virus transmission for all study years and was
      most highly correlated with sentinel seroconversions 4 wk later. The utility of
      vectorial capacity and its component variables is discussed for this system.

PMID- 11296824
TI  - Fleas (siphonaptera) collected from small mammals in Southern Viet Nam in 1997
      1998.
AB  - We report on fleas collected from small mammals in two forests, a lowland
      semideciduous dipterocarp forest and a highland evergreen forest, in southern
      Viet Nam. In the lowland forest, only one species of flea (Xenopsylla vexabilis
      Jordan) infested a single species of rodent [Berylmys berdmorei (Blyth)]. In the
      highland forest, seven species of fleas were collected from eight species of
      small mammals. Three species of fleas, Lentistivalius insolli (Traub),
      Lentistivalius occidentayunnanus Li, Xie & Gong, and Gryphopsylla jacobsoni
      (Jordan & Rothschild), collected from mammals in the highland forest represent
      new records for Viet Nam.

PMID- 11296825
TI  - Interactions between Triatoma infestans and Triatoma sordida (Hemiptera:
      Reduviidae) in artificial ecotopes: population growth and age structure.
AB  - Interaction characteristics between Triatoma infestans Klug, 1834 and Triatoma
      sordida Stal, 1859 populations were studied in artificial ecotopes for 16 mo. The
      experimental design involved simultaneous treatments with T. infestans and T.
      sordida together in the same experimental unit (EU) and each separately in two
      control units (CU) made of adobe bricks. Chickens were used as host animals. Each
      unit was dismantled monthly to estimate triatomine population size and age
      structure, rebuilt, and repopulated with the same insects. In both units, T.
      infestans population growth followed a logistic model, whereas T. sordida did not
      show this pattern. T. infestans completed a generation in 24 wk (EU) and 32 wk
      (CU1), whereas T. sordida did not complete one generation during this period. We
      concluded that T infestans showed a better colonizing success than T. sordida.
      After living together for 1 yr, an interference process took place that resulted
      in the extinction of T. sordida.

PMID- 11296826
TI  - Genetic differentiation among populations of house flies (Diptera: Muscidae)
      breeding at a multiple-barn, egg-laying facility in central Minnesota.
AB  - Mitochondrial gene diversity was used in house fly, Musca domestica L.,
      populations to examine gene flow within and among 16 sealed barns in a large egg
      laying facility in Renville, MN. Haplotypes in poultry barns were compared with
      those in outdoor house fly populations nearby and in St. Paul, MN. Haplotype
      diversities were greater in the closed than in the open populations. There was
      significant gene flow among poultry barns, and export of flies from barns was
      observed. Nevertheless, of three haplotypes detected in the closed populations,
      one was undetected in the open populations. A significant change in haplotype
      frequencies within poultry barns between years is attributed to genetic drift.
      The geographical origin of one haplotype is obscure.

PMID- 11296828
TI  - Ticks (Acari: Ixodidae) and spirochetes (spirochaetaceae: spirochaetales)
      recovered from birds on a Georgia Barrier Island.
AB  - From September 1997 through July 1999, 300 individuals and 46 species of birds
      were mist-netted and screened for ticks and spirochetes on St. Catherine's
      Island, Liberty County, GA. Seventy-six (25%) of the birds were parasitized by a
      meal intensity of 4.6 ticks. Seasonally, more birds were infested with ticks
      during the summer (50% in 1998, 34% in 1999) than in spring (15% in 1998, 11% in
      1999) or fall (21% in 1997, 20% in 1998), mainly because of severe infestations
      on some birds by immature stages of the lone star tick, Amblyomma americanum
      (L.), during this season. Eight species ofticks were recovered from 14 species of
      birds during this study: A. americanum (74 nymphs, 168 larvae); the blacklegged
      tick, Ixodes scapularis Say (11 nymphs, 28 larvae), the Gulf Coast tick,
      Amblyomma maculatum Koch (two nymphs, 29 larvae); Ixodes minor Neumann (16
      larvae); the rabbit tick. Haemaphysalis leporispalustris (Packard) (one nymph, 14
      larvae); the bird tick Ixodes brunneus Koch (two larvae); the American dog tick,
      Dermacentor variabilis (Say) (one nymph); and Ixodes affinis Neumann (one larva).
      The Carolina wren was parasitized by more species of ticks (seven) than any other
      bird species, followed by the northern cardinal (five), white-throated sparrow
      (four) and painted bunting (three). Spirochetes were isolated in BSK II medium
      from one tick (a nymphal A. americanum) and from skin biopsies of 12 (4%) of the
      individual birds (three downy woodpeckers, three northern waterthrushes, two
      Carolina wrens, one American redstart, one pine warbler, one Swainson's thrush,
      and one white-eyed vireo) all in fall 1997. This concentrated phenology of
      spirochete isolations might reflect periodic amplification or recrudescence of
      spirochetes in reservoir avian hosts.

PMID- 11296827
TI  - Localization of midgut-specific protein antigens from Aedes aegypti (Diptera:
      Culicidae) using monoclonal antibodies.
AB  - Most insect transmitted pathogens interact with the midgut of their vectors for
      infection and, in some cases, development. Therefore, molecules associated with
      the midgut epithelium in direct contact with pathogens may be potential targets
      of infection-blocking measures. Here, we identify midgut-specific protein
      antigens from Aedes aegypti (L.) using monoclonal antibodies. Sixty-four
      monoclonal antibodies were generated with reactivity to the mosquito midgut, five
      of which are reported in this article. Three monoclonal antibodies identified
      protein antigens localized at the midgut epithelial surface (the brush border)
      and the peritrophic membrane. In addition, two monoclonal antibodies recognized
      mosquito nucleus-specific proteins by immunofluorescence microscopy. Because
      potential target antigens for blocking transmission of pathogens most likely are
      located at the interface of mosquito-pathogen interactions, these monoclonal
      antibodies could provide valuable tools for studying midgut-specific proteins and
      interactions of the mosquito midgut with pathogens.

PMID- 11296829
TI  - Wolbachia infections of phlebotomine sand flies (Diptera: Psychodidae).
AB  - Old and New World phlebotomine sand fly species were screened for infection with
      Wolbachia, intracellular bacterial endosymbionts found in many arthropods and
      filarial nematodes. Of 53 samples representing 15 species, nine samples offour
      species were found positive for Wolbachia by polymerase chain reaction
      amplification using primers for the Wolbachia surface protein (wsp) gene. Five of
      the wsp gene fragments from four species were cloned, sequenced, and used for
      phylogenetic analysis. These wsp sequences were placed in three different clades
      within the arthropod associated Wolbachia (groups A and B), suggesting that
      Wolbacia has infected sand flies on more than one occasion. Two distantly related
      sand fly species, Lutzomyia (Psanthyromyia) shannoi (Dyar) and Lutzomyia
      (Nyssomyia) whitmani (Antunes & Coutinho), infected with an identical Wolbachia
      strain suggest a very recent horizontal transmission.

PMID- 11296830
TI  - Attraction of Anopheles (Diptera: culicidae) to volatile chemicals in Western
      Kenya.
AB  - Anopheles gambiae s.l. and Anopheles funestus Giles are the primary vectors of
      malaria in East Africa. Identification of host-location olfactory cues may
      increase trap sensitivity for vector control and surveillance programs. Solid
      state army miniature light traps were operated near sleeping humans in huts at
      night without lights and augmented with the potential attractants: L-lactic acid,
      Limburger cheese volatiles, hexanoic acid, and carbon dioxide. Mosquito response
      varied between species and gender. Female An. funestus exhibited a greater
      response to traps baited with L-lactic acid in combination with carbon dioxide
      than carbon dioxide alone in two different experiments.

PMID- 11296831
TI  - Analysis of specific adaptation to a domicile habitat: a comparative study of two
      closely related cockroach species.
AB  - The German cockroach, Blattella germanica (L.), and the closely related species
      B. bisignata (Brunner) belong to the germanica species group. They are similar in
      appearance, life history, reproductive cycle, and courtship behavior. The most
      significant difference is habitat preferences: B. germanica is a household
      species and lives in crowded conditions, whereas the feral B. bisignata lives
      outdoors in a solitary manner. Nevertheless, B. bisignata has recently been found
      in households. A comparison between the two species has shown that B. germanica
      displays gregarious behavior and produces an aggregation pheromone, whereas both
      characters are absent in B. bisignata. Mate preference experiments have revealed
      that B. germanica females accepted only conspecific males, whereas B. bisignata
      females mated with males from both species, provided that long distance calling
      was bypassed. In addition, the high reproductive potential of B. germanica
      outcompeted the other species: when 10 pairs of B. germanica and of B. bisignata
      were kept together in crowded conditions during 3 mo, B. bisignata was driven
      into extinction. It is concluded that the chances of B. bisignata becoming a new
      household species are remote.

PMID- 11296832
TI  - Winter biology of Aedes albifasciatus (Diptera: Culicidae) from Cordoba,
      Argentina.
AB  - Host-seeking females of Aedes albifasciatus (Macquart) were collected from April
      to September 1997, kept under seminatural conditions, and offered sugar solution
      and blood. Daily survival of females ranged from 0.91 to 0.96, with blood fed
      females living longer than sugar fed females. Overall, 43% of engorged females
      completed a gonotrophic cycle, and 15% of them refed and completed a second
      gonotrophic cycle. The life expectancy of females emerging at the end of summer
      was longer than those that emerged during winter. Immature developmental time and
      the developmental threshold were estimated by regression. Embryo development was
      recorded during autumn, winter, and spring, with a duration of 5-9 d. The
      developmental threshold for eggs was estimated to be 2.28 degrees C. Egg
      mortality varied from 0.51 to 0.74. The development time for larva and pupa was
      between 16 and 29 d and was significantly correlated with temperature. The
      developmental threshold for larvae and pupae was estimated to be 4.75 degrees C.
      A greater proportion of females than males emerged when temperatures averaged <
      or = 18 degrees C. Larval and pupal mortality was high at temperatures below the
      developmental threshold. Aedes albifasciatus females remained gonotrophically
      active and immature development continued during winter in Cordoba (10 degrees C
      isotherm).

PMID- 11296833
TI  - Distribution of phlebotomine sand fly genotypes (Lutzomyia shannoni, Diptera:
      Psychodidae) across a highly heterogeneous landscape.
AB  - Genetic variability of eight Colombian field populations and two laboratory
      colonies of a tropical forest sand fly, Lutzomyia shannoni Dyar, was assessed by
      comparing allozyme frequencies at 20 enzyme loci. Substantial genetic variability
      was noted in all strains, with mean heterozygosities of 13-21% and alleles per
      locus of 2.0-2.8. Four loci were monomorphic. Six populations in north and
      central Colombia showed close genetic similarity (Nei's distances, 0.01-0.09),
      despite mountainous environment, discontinuous forest habitat, and elevation
      differences from 125 to 1,220 m. Two samples representing the Orinoco (near
      Villavicencio) and Amazon (near Leticia) river basins were similar (Nei's
      distance, 0.08) but diverged substantially from the central six samples (Nei's
      distances, 0.26-0.40). Although the range of L. shannoni extends from the
      southeastern United States to northern Argentina, three genetically distinct,
      geographically discrete, groups were discerned by the current analysis: Orinoco
      Amazon river basins, north-central Colombia, and eastern United States.

PMID- 11296834
TI  - Population dynamics of sand flies (diptera: psychodidae) at two foci of
      leishmaniasis in Texas.
AB  - Sand flies were collected at a focus of leishmaniasis in Medina County, TX, from
      April through October 1997 and at a focus in Bexar County, TX, from April 1998
      through December 1999. Lutzomyia diabolica (Hall) were collected from April
      through November with peak abundance in July. The male:female ratio of Lu.
      diabolica was 1:6.2. Almost all female Lu. diabolica in the collections were
      unfed. One gravid Lu. diabolica contained 49 ova. Female Lu. anthophora (Addis)
      were active from February through December with three peaks in abundance
      suggestive of successive generations. Unfed and gravid Lu. anthophora were
      collected in about equal numbers. Gravid females contained from 1 to 64 ova per
      female. The male:female ratio was 1:1.8, with male Lu. anthophora collected in
      all months. One female Lu. anthophora was found infected with Leishmania in July
      1999. Lutzomyia texana (Dampf) were collected from April through October with
      peak abundance in April during 1997. The male:female ratio was 1:1.4, with most
      females unfed. Two gravid Lu. texana contained 32 and 102 ova. An undescribed
      species of Lutzomyia was found only at the Medina County site from May through
      September 1997. Trapping sites four times per month versus two times per month in
      1999 did not appear to adversely affect the abundance of Lu. diabolica or Lu.
      anthophora. There were marked differences in the species composition and relative
      abundance at the different sites, indicating that the spatial distribution of
      sand flies is patchy in nature.

PMID- 11296835
TI  - Larval production from field-collected Carcinops pumilio (Coleoptera: Histeridae)
      following three starvation periods.
AB  - Carcinops pumilio (Erichson) were collected from high-rise, caged-layer poultry
      facilities using two trapping methods, a blacklight pitfall trap and a mesh
      bottomed trap placed on poultry manure. Starvation for 14 d significantly reduced
      larval production during the first 3-d oviposition period regardless of trapping
      method. Beetles collected with blacklight traps and subsequently starved for 14 d
      had higher larval production in the third through fifth oviposition periods than
      those fed daily, indicating that lack of nutrition was a limiting factor in C.
      pumilio larval production. No differences were observed in larval production,
      after the first oviposition period, between the 14-d starved and daily fed groups
      collected with the mesh-bottom trap. In all blacklight-captured treatments,
      larval production was lowest during the first oviposition period with the largest
      differences found among the three starved treatments. Larval production in the 14
      d starved treatment increased significantly during the later oviposition periods
      in mesh-bottom trap studies. Within the fed treatment, larval production was
      consistently greater among beetles collected with the mesh-bottom trap than among
      beetles collected with blacklight traps.

PMID- 11296836
TI  - Characteristics of larval anopheline (Diptera: Culicidae) habitats in Western
      Kenya.
AB  - A longitudinal survey of mosquito larval habitats was carried out in Asembo Bay,
      western Kenya, during the rainy season of 1998. All pools of standing water along
      a 700-m transect were sampled twice per week. For each habitat, eight
      environmental variables were recorded and a sample of anopheline larvae was
      collected for identification. In total, 1,751 Anopheles gambiae s.l. and 2,784
      Anopheles funestus Giles were identified. Identification of An. gambiae s.l. by
      polymerase chain reaction (PCR) indicated that 240 (14.7%) were An. gambiae Giles
      and 858 (52.4%) were An. arabiensis Patton; PCR failed to identify 539 (32.9%)
      specimens. Repeated measures logistic regression analysis indicated that An.
      gambiae and An. arabiensis larvae were associated with small, temporary habitats
      with algae and little or no aquatic vegetation. Anopheles funestus larvae were
      associated with larger, semipermanent bodies of water containing aquatic
      vegetation and algae. Direct comparison of habitat characteristics associated
      with either An. gambiae or An. arabiensis revealed that algae were associated
      more commonly with habitats containing An. gambiae; no other differences were
      detected. Chi-square analysis indicated that these species were collected from
      the same habitat more frequently than would be expected by chance alone.
      Together, these results indicate that An. gambiae and An. arabiensis have similar
      requirements for the larval environment and that, at least in western Kenya, they
      do not segregate into separate habitats.

PMID- 11296837
TI  - Prevalence of sindbis virus neutralizing antibodies among Swedish passerines
      indicates that thrushes are the main amplifying hosts.
AB  - The Sindbis virus uses birds as vertebrate hosts in the summer amplification
      cycle, and the virus is transmitted by ornithophilic Culex species. Previous
      field and experimental studies have shown that mainly passerine birds are
      involved in the amplification. To delineate the pattern of Sindbis virus
      infections among passerines, we collected and sampled birds for blood at five
      study sites located in northern, central, and southern Sweden. All study sites
      were lowland forested wetlands and humid forests. The blood samples were assayed
      for Sindbis neutralizing antibodies, and we tested if the prevalence of Sindbis
      antibodies varied in relation to bird characteristics (i.e., species, body-mass,
      sex, and age), and environmental factors (i.e., year, month, and location). We
      found that Sindbis virus infections occurred in almost all passerine species
      sampled, but that the infection prevalence was unequally distributed among
      species. The fieldfare, the redwing, and the songthrush each had significantly
      higher prevalence than the average for all species. Large passerine species had
      higher infection prevalence than small species. The infection was less prevalent
      in hatching-year birds than in older birds during June and July, but not in
      August. Males and females had the same infection prevalence. The prevalence of
      Sindbis antibodies was higher in central than in southern Sweden, which coincided
      with a higher proportion of fieldfare-redwing-songthrush samples in the central
      region of the country. Thus, it is possible that regional and annual variations
      in the prevalence of Sindbis antibodies in Swedish passerine species depend on
      the number of fieldfares, redwings, and songthrushes available for feeding by
      vector mosquitoes.

PMID- 11296838
TI  - Characterization of acaricide resistance in Rhipicephalus sanguineus (latreille)
      (Acari: Ixodidae) collected from the Corozal Army Veterinary Quarantine Center,
      Panama.
AB  - Rhipicephalus sanguineus (Latreille) were collected from the Corozal Army
      Veterinary Quarantine Center in Panama and characterized for resistance to five
      classes of acaricides. These ticks were highly resistant to permethrin, DDT, and
      coumaphos; moderately resistant to amitraz; and not resistant to fipronil when
      compared with susceptible strains. Resistance to both permethrin and DDT may
      result from a mutation of the sodium channel. However, synergist studies indicate
      that enzyme activity is involved. The LC50 estimate for permethrin was lowered
      further in the Panamanian strain then in susceptible strains with the addition of
      triphenylphosphate (TPP), but not with the addition ofpiperonyl butoxide (PBO).
      This suggests that esterases and not oxidases are responsible for at least some
      pyrethroid resistance. Elevated esterase activity and its inhibition by TPP were
      confirmed by native gel electrophoresis. The LC50 estimate obtained for coumaphos
      in the Panamanian strain was not lowered further than what was observed for
      susceptible strains by the addition of TPP or PBO. This indicates that enzyme
      activity might not be involved in coumaphos resistance. Resistance to amitraz was
      measured through a modification of the Food and Agriculture Organization Larval
      Packet Test. All tick strains were found to be susceptible to fipronil.

PMID- 11296839
TI  - Blood host sources of Mepraia spinolai (Heteroptera: Reduviidae), wild vector of
      chagas disease in Chile.
AB  - There are two vectors of the Chagas' disease in Chile: Triatoma infestans Klug
      the domestic vector and Mepraia spinolai Porter the sylvatic vector. The
      alimentary profile of M. spinolai has been poorly studied. In this work we study
      the participation of humans, goats, dogs, cats, rodents, rabbits, birds (hens)
      and reptiles in the diet of M. spinolai by analyzing the intestinal content
      through immunoradiometric assay. To put our results in a general context, we also
      compared the diet with that described for T. infestans. In decreasing order, we
      detected blood of rabbits, dogs, goats, rodents, humans, and birds (hens). There
      were 12.3% of insects infected with T. cruzi, but this fact was not significant
      for diet variance. In warm weather there was a larger diversity of alimentary
      sources than in a cold one. The niche breadth increased from 0.029 in cold
      weather to 0.464 in warm weather. The niche overlap of T. infestans and M.
      spinolai was 0.23.

PMID- 11296840
TI  - Detection of Orientia tsutsugamushi (Rickettsiales: rickettsiaceae) in unengorged
      chiggers (Acari: Trombiculidae) from Oita Prefecture, Japan, by nested polymerase
      chain reaction.
AB  - The current study surveyed the 56-kDa type-specific antigen (TSA) gene DNAs of
      Orientia tsutsugamushi (Hayashi) in approximately 4.000 unengorged chiggers
      obtained from the soil or ground surface in an endemic and a nonendemic area of
      the Tsutsugamushi disease in Oita Prefecture, southwestern Japan, by nested
      polymerase chain reaction (PCR). Serotypes of O. tsutsugamushi were identified by
      restriction fragment-length polymorphism (RFLP) analysis. In the endemic area,
      242 pools from five species [234 pools of Leptotrombidium scutellare (Nagayo,
      Miyagawa, Mitamura, Tamiya and Tenjin), two L. pallidum (Nagayo, Miyagawa,
      Mitamura and Tamiya), four L. kitasatoi (Fukuzumi & Obata), one L. fuji (Kuwata,
      Berge and Philip), and one Neotrombicula japonica (Tanaka, Kaiwa, Teramura and
      Kagaya)] were tested, and eight (seven pools of L. scutellare and one N.
      japonica) were positive for O. tsutsugamushi. Among the seven positive pools of
      L. scutellare, the distribution of serotypes was as follows: Kuroki (4), Gilliam
      (1), Karp (1), and Kawasaki (1). The first two serotypes (Kuroki and Gilliam)
      were identified for the first time in this species. In the nonendemic area, 128
      pools from eight species were tested, and 13 were positive for O. tsutsugamushi.
      The positive rate was as follows: L. pallidum (4/41). L. kitasatoi (1/18),
      Gahrliepia saduski Womersley (2/10), L. fuji (4/50), L. himizu (Sasa, Kumada,
      Hayashi, Enomoto, Fukuzumi and Obata) (1/2), and Miyatrombicula kochiensis (Sasa,
      Kawashima and Egashira) (1/3). The latter three species were shown for the first
      time to harbor O. tsutsugamushi. All ofthe positive pools were Kuroki, except for
      two pools (one L. pallidum and one L. fuji), which were Gilliam (this serotype
      was also detected for the first time in L. pallidum). Further analysis revealed
      no differences in the nucleotide sequences (125 bp of variable domain 1 of TSA
      gene) of the same serotypes (i.e., Kuroki and Gilliam) among the positive
      samples. These data indicate that O. tsutsugamushi was widely distributed in
      various trombiculid species, even in the nonendemic area. The data are also
      suggestive of a possible horizontal transmission of O. tsutsugamushi among
      trombiculid species.

PMID- 11296842
TI  - Effects of selected meterological factors on diurnal questing of Ixodes
      scapularis and Amblyomma Americanum (Acari: Ixodidade).
AB  - The diurnal questing behavior of adult Ixodes scapularis Say and Amblyomma
      americanum (L.) were monitored in the field to determine whether ticks would be
      collected with greater frequency during certain times of the day and under
      certain ambient meteorological conditions. Temperature and relative humidity
      explained a significant amount of the total variation in tick collections.
      Although both species were collected during every period, I. scapularis adults
      tended to quest earlier and later in the day when temperatures were lower and
      relative humidity higher, whereas A. americanum were collected with greater
      frequency in late morning and early afternoon during periods of higher
      temperatures and lower humidity. Questing of I. scapularis adults was observed at
      temperatures as low as -0.6 degrees C, whereas no adult A. americanum were
      collected below 4.4 degrees C. The questing temperature threshold for I.
      scapularis adults observed in this study was below that reported previously. The
      implications of these temporal activity patterns on the assessment of disease
      transmission risk and sampling bias are also discussed.

PMID- 11296841
TI  - Effects of Plagiorchis elegans (Trematoda: Plagiorchiidae) infection on the
      carbohydrate metabolism of fourth instar Aedes aegypti (Diptera: Culicidae).
AB  - Infection of fourth-instar Aedes aegypti (L.) with the entomopathogenic digenean
      Plagiorchis elegans (Rudolphi) alters the carbohydrate metabolism of the insect.
      Within 24 h of cercarial penetration, total body extracts of infected fourth
      instars exhibited decreased trehalase activity, increased trehalose-6-phosphatase
      activity, and a concomitant accumulation of trehalose when compared with
      uninfected larvae. The amounts of glucose, glycogen and lipids, and the activity
      of glycogen phosphorylase a were similar in extracts of infected and control
      larvae. The predominant fatty acids, in both control and infected larvae, were C
      18:0, C 18:1, and C 18:3. There were no significant differences in the types or
      proportions of fatty acids found in control and infected larvae. Parasitic
      infection is discussed in terms of impaired trehalose metabolism.

PMID- 11296843
TI  - Landscape affects the host-seeking patterns of Culex tarsalis (Diptera:
      Culicidae) in the Coachella Valley of California.
AB  - Effective arbovirus transmission requires that the principal vertebrate hosts and
      vectors have frequent contact. Vegetation and other landscape features used by
      roosting or nesting birds at night dictate their exposure to nocturnally active
      host-seeking Culex tarsalis Coquillett and therefore to western equine
      encephalomyelitis and St. Louis encephalitis viruses. Precipitin tests on 645 Cx.
      tarsalis that were collected resting and host-seeking near the Salton Sea in
      Coachella Valley, CA, indicated that passeriform birds (64%) and rabbits (25%)
      were the most frequent bloodmeal hosts and that the percentage of females feeding
      on birds varied temporally as an inverse fuction of mosquito abundance. Blood
      meals were not taken from communally roosting water birds. The spatial
      distribution of host-seeking females then was investigated by deploying dry ice
      baited traps within seven sites representative of habitats found along the Salton
      Sea. Mosquito catch was greatest at traps within elevated vegetation such as
      Tamarisk, mesquite, cattails, and orchards and lowest at traps positioned at
      snags over water, sand bars, open fields, and within housing in a small rural
      community. These data indicate that host-seeking Cx. tarsalis females congregated
      at specific landscape features that were not necessarily associated with large
      concentrations of potential bloodmeal hosts.

PMID- 11296844
TI  - Vector competence of Musca domestica (Diptera: Muscidae) for Yersinia
      pseudotuberculosis.
AB  - The vectoR potential of adult house flies. Musca domestica L., for Yersinia
      pseudotuberculosis (Pfeiffer), a pathogen of domestic animals and humans, was
      investigated. Adult flies were allowed to feed on trypticase soy broth (TSB)
      containing Y. pseudotuberculosis for 6 h and then transferred to sterile
      containers with sterile TSB as a source of water and nutrients. At 6-h intervals,
      all flies were transferred to sterile containers with sterile TSB and 10 randomly
      selected flies were examined for the pathogen. Yersinia pseudotuberculosis did
      not establish a permanent population in the house fly colony; however, viable
      cells were detected from the digestive tract of flies for up to 36 h after the
      initial exposure, and flies contaminated their environment (sterile TSB) for up
      to 30 h after the exposure. These results demonstrated that house flies can carry
      Y. psedotuberculosis for a considerable period and therefore must be considered
      as a potential mechanical vector of pseudotuberculosis infection.

PMID- 11296845
TI  - Microsatellite DNA polymorphism and heterozygosity among field and laboratory
      populations of Anopheles gambiae ss (Diptera: Culicidae).
AB  - We compared microsatellite polymorphism at nine loci located on chromosome 3
      among two colonies and a field population of Anopheles gambiae sensu stricto
      Giles mosquitoes. Numbers of microsatellite alleles observed at each locus and
      mean heterozygosities were drastically reduced among laboratory colonies. Genetic
      analysis of the field population used in this study revealed an unprecedented
      frequency of rare alleles (<0.05). In contrast, colony samples revealed large
      numbers of alleles with frequencies >0.50. Partitioning of field data to assess
      the impact of rare alleles, null alleles, and sample size on estimates of mean
      heterozygosity revealed the plasticity of this measurement and suggests that
      heterozygosity may be reliably estimated from relatively small collections using
      microsatellites.

PMID- 11296846
TI  - Occurrence of Anopheles hermsi (Diptera: Culicidae) in Arizona and Colorado.
AB  - Historically, malaria was a significant cause of morbidity and mortality
      throughout the western United States, and Anopheles freeborni Aitken was thought
      to be the vector west of the Continental Divide. In 1989, Anopheles hermsi Barr &
      Guptavanij was described and subsequently found to be an effective laboratory
      vector of Plasmodium. The adults of these two species are morphologically
      indistinguishable, and therefore polymerase chain reaction was used to analyze
      the DNA from 48 mosquitoes collected in Arizona and Colorado (identified
      morphologically as An. freeborni). All specimens were identified as An. hermsi.
      This was the first report of An. hermsi in Arizona and Colorado and indicated
      that this Anopheles species historically may have been a malaria vector in these
      two western states.

PMID- 11296847
TI  - Efficacy of granular deltamethrin against Ixodes scapularis and Amblyomma
      americanum (Acari: Ixodidade) nymphs.
AB  - A single barrier application of granular deltamethrin to the woodland edges of a
      forested residential community in late spring significantly reduced the abundance
      of Ixodes scapularis Say nymphs. The application also suppressed the population
      of Amblyomma americanum (L.) nymphs, which recently became established in the
      study area. The efficacy of deltamethrin is compared with other commonly used
      acaricides.

PMID- 11296848
TI  - Edward H. Bloch, M.D., Ph.D. Pioneer in the microscopic study of, and the
      microcirculation of, living tissues and organs.
AB  - Edward H. Bloch, M.D., Ph.D., Professor Emeritus of Anatomy, School of Medicine,
      Case Western Reserve University, died 3 November 2000 in Cleveland, Ohio at the
      age of 86. Known to his friends as "Maxl," he will be greatly missed by his
      friends, colleagues and former students.

PMID- 11296849
TI  - Soluble P-selectin antagonist mediates rolling velocity and adhesion of
      leukocytes in acutely inflamed venules.
AB  - OBJECTIVE: Leukocyte rolling is recognized as an important event in facilitating
      the extravasation of leukocytes from the vascular to the interstitial
      compartment, and is mediated by the selectin family of cell adhesion molecules.
      The aim of this study was to evaluate and characterize the rolling behavior of
      leukocytes in a model of acute inflammation using a novel soluble selectin ligand
      directed against P-selectin. METHODS: Feline mesenteric postcapillary venules
      were visualized using intravital microscopy prior to and following exposure to
      leukotriene C4 (LTC4) in animals pretreated with vehicle (saline) and the P
      selectin antagonist rPSGL-Ig. RESULTS: A concentration of 500 pM LTC4 induced a
      threefold and sixfold elevation in leukocyte rolling flux and adhesion,
      respectively, compared to baseline values (p < 0.05). Administration of rPSGL-Ig
      had no effect on LTC4-induced leukocyte rolling flux but significantly attenuated
      the increase in the fraction of rolling leukocytes (p < 0.05). In addition, rPSGL
      Ig inhibited the LTC4-induced reductions in leukocyte rolling velocity (p <
      0.001). Finally, LTC4-induced leukocyte adhesion in animals pretreated with rPSGL
      Ig was reduced by 60%, compared to vehicle-treated animals (p < 0.05).
      CONCLUSIONS: LTC4 induces leukocyte rolling and adhesion in feline mesenteric
      venules in a dose-dependent manner. Administration of rPSGL-Ig inhibits LTC4
      induced reductions in leukocyte rolling velocity and attenuates the elevation in
      the fraction of rolling leukocytes produced by LTC4 stimulation. This suggests
      that rPSGL-Ig may be used to reduce leukocyte rolling and adhesion, and
      subsequently attenuate tissue injury during inflammation.

PMID- 11296850
TI  - Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expression during
      microvascular remodeling in rat skeletal muscle.
AB  - OBJECTIVE: The process of microvessel growth and remodeling depends on the
      presence of matrix metalloproteinases (MMPs) in a specific spatial pattern of
      expression. This study characterizes the spatial distribution of
      metalloproteinase-9 (MMP-9) expression during microvascular remodeling in the rat
      spinotrapezius muscle. METHODS: Female Sprague-Dawley rats (4 weeks old) were
      administered the alpha1-adrenergic blocker prazosin for 7 days to induce chronic
      vasodilation and associated increases in capillary and arteriolar density. MMP-9
      expression was analyzed by Western blotting analysis of microdissected regions of
      muscle and immunolabeling of muscle sections. RESULTS: Capillary density
      expressed as both capillary-to-fiber ratio (C/F) and capillaries per mm2
      increased significantly (p < 0.01) due to prazosin administration. Western
      blotting on microdissected regions of spinotrapezius muscle showed that there was
      an increase in MMP-9 expression in prazosin-treated animals. Additionally, the
      Western blots showed a presence of the activated form of MMP-9 in regions of
      spinotrapezius muscle containing vessels on the order of capillaries and small
      arterioles. Immunohistochemistry demonstrated that MMP-9 significantly increased
      in the muscles of treated animals in areas within the vessel walls of
      microvessels greater than 20 microm in diameter. However, interstitial MMP-9
      expression did not significantly increase with prazosin administration.
      CONCLUSIONS: These results demonstrate that the expression of MMP-9 increases
      during in vivo microvascular remodeling in adult skeletal muscle. The MMP-9
      expression is limited to larger (>20-microm diameter) microvessels, suggesting a
      role for MMP-9 in the remodeling of such vessels during prazosin-induced
      vasodilation and the subsequent capillary proliferation.

PMID- 11296851
TI  - Simulating the spread of membrane potential changes in arteriolar networks.
AB  - OBJECTIVE: Our aim was to simulate the spread of membrane potential changes in
      microvascular trees and then make the simulation programs accessible to other
      researchers. We have applied our simulations to demonstrate the implications of
      electrical coupling between arteriolar smooth muscle and endothelium. METHODS: A
      two-layered, cable-like model of an arteriole was used, and the assumptions
      involved in the approach explicitly stated. Several common experimental
      situations that involve the passive spread of membrane potential changes in
      microvascular trees were simulated. The calculations were performed using NEURON,
      a well-established computer simulation program that we have modified for use with
      vascular trees. RESULTS: Simulated results show that membrane potential changes
      would probably not spread as far in the endothelium as they would in the smooth
      muscle of arterioles. Where feed arteries are connected to larger distributing
      arteries, passive spread alone may not explain the physiologically observed
      spread of diameter changes. CONCLUSIONS: Simulated results suggest that the
      morphology of an arteriole, in which the muscle layer is much thicker than the
      endothelium, favors electrical conduction along smooth muscle rather than the
      endothelium. However, it seems that passive electrical spread is insufficient to
      explain the apparent spread of membrane potential changes in experimental
      situations. Active responses involving voltage-dependent conductances may be
      involved, and these can also be included in our simulation.

PMID- 11296852
TI  - 20-HETE contributes to myogenic activation of skeletal muscle resistance arteries
      in Brown Norway and Sprague-Dawley rats.
AB  - OBJECTIVE: To evaluate the role of 20-hydroxyeicosatetraenoic acid (20-HETE), a
      product of arachidonic acid omega-hydroxylation via cytochrome P450 (CP450) 4A
      enzymes, in regulating myogenic activation of skeletal muscle resistance arteries
      from normotensive Brown Norway (BN) and Sprague-Dawley (SD) rats. METHODS:
      Gracilis arteries (GA) were isolated from each animal, viewed via television
      microscopy, and vessel diameter responses to elevated transmural pressure were
      measured with a video micrometer under control conditions and following
      pharmacological inhibition of the CP450 4A enzyme system. RESULTS: Under control
      conditions, GA from both rat groups exhibited strong, endothelium-independent
      myogenic activation, which was impaired following treatment with either 17
      octadecynoic acid (17-ODYA) or dibromo-dodecenylmethylsulfimide (DDMS), two
      mechanistically different inhibitors of 20-HETE production. The addition of
      tetraethylammonium (KCa channel inhibitor) to 17-ODYA-treated GA restored
      myogenic reactivity to levels comparable to those under control conditions.
      Treatment of GA from BN and SD rats with 6(Z),15(Z)-20-HEDE, a selective
      antagonist for 20-HETE receptors, mimicked the effects of 17-ODYA and DDMS
      treatment on myogenic reactivity. CONCLUSIONS: These results suggest that the
      production of 20-HETE via CP450 4A enzymes contributes to the myogenic activation
      of skeletal muscle resistance arteries from normotensive BN and SD rats. 20-HETE
      may act through a receptor-mediated process to block vascular smooth muscle KCa
      channels in response to the elevated transmural pressure.

PMID- 11296853
TI  - Pancreatic enzymes and microvascular cell activation in multiorgan failure.
AB  - Cell activation in the microcirculation leads to an inflammatory cascade and is
      accompanied by many cardiovascular complications. There is a need to identify the
      trigger mechanisms that lead to the production of in vivo activating factors. We
      review here mechanisms for cell activation in the microcirculation and
      specifically the production of humoral cell activators in physiological shock.
      The elevated levels of activating factors in plasma could be traced to the action
      of pancreatic enzymes in the ischemic intestine. New interventions against the
      production of the activators are proposed. The evidence suggests that pancreatic
      enzymes in the ischemic intestine may attack several tissue components and
      generate cellular activators that are associated with multiorgan dysfunction in
      physiological shock.

PMID- 11296854
TI  - Angiogenesis induced by electrical stimulation is mediated by angiotensin II and
      VEGF.
AB  - OBJECTIVE: Physiological angiogenesis in skeletal muscle is an adaptive response
      to physical training and electrical stimulation. This study investigated the role
      of angiotensin II (Ang II) in regulating both angiogenesis and vascular
      endothelial growth factor (VEGF) protein expression induced by electrical
      stimulation. METHODS: The right tibialis anterior (TA) and extensor digitorum
      longus (EDL) muscles of Sprague-Dawley rats were stimulated for 8 hours per day
      for 7 days. The contralateral muscles served as controls. Two days before the
      surgery and throughout the stimulation protocol, the rats received either
      lisinopril or losartan in their drinking water. Rats without any drug treatment
      were used as control. Immunohistochemistry and Western blot analysis were
      performed to identify the source and quantify the VEGF protein expression in
      these muscles. The relationship between angiogenesis and VEGF expression was
      explored using a VEGF-neutralizing antibody. RESULTS: Chronic electrical
      stimulation of the skeletal muscles led to significant increases in vessel
      density (14% and 30% for EDL and TA, respectively) within 7 days. In addition,
      stimulation increased VEGF protein levels in the stimulated muscles. Both
      lisinopril and losartan blocked elevation in VEGF expression and inhibited the
      angiogenesis induced by stimulation. VEGF neutralization also inhibited
      angiogenesis, confirming the relationship between Ang II, VEGF, and vessel
      growth. CONCLUSION: The current study suggests a pathway involving angiotensin II
      receptors (AT1) and VEGF in electrically stimulated angiogenesis.

PMID- 11296855
TI  - Reproductive potential predicts longevity of female Mediterranean fruitflies.
AB  - Reproduction exacts a price in terms of decreased survival. Our analysis of the
      interplay between age patterns of fecundity and mortality for individual female
      medflies (Ceratitis capitata) revealed that individual mortality is associated
      with the time-dynamics of the egg-laying trajectory. In a sample of 531 medflies,
      we found that each individual has a characteristic rate of decline in egg laying
      with age. This defines an individual's rate of reproductive exhaustion. This rate
      was shown to predict subsequent mortality The larger the remaining reproductive
      potential, the lower the subsequent mortality An increased mortality risk was
      seen in flies for which egg production declined rapidly early on, irrespective of
      the level of egg production. Thus, reproductive potential and lifetime are
      coupled in such a way that those flies which are able to profit most from an
      extended life span in terms of increased egg output are indeed likely to live
      longer.

PMID- 11296856
TI  - Dispersed activation in the left temporal cortex for speech-reading in
      congenitally deaf people.
AB  - Does the lateral temporal cortex require acoustic exposure in order to become
      specialized for speech processing? Six hearing participants and six congenitally
      deaf participants, all with spoken English as their first langugage, were scanned
      using functional magnetic resonance imaging while performing a simple speech
      reading task. Focal activation of the left lateral temporal cortex was
      significantly reduced in the deaf group compared with the hearing group.
      Activation within this region was present in individual deaf participants, but
      varied in location from person to person. Early acoustic experience may be
      required for regions within the left temporal cortex in order to develop into a
      coherent network with subareas devoted to specific speech analysis functions.

PMID- 11296857
TI  - Avian evolution, Gondwana biogeography and the Cretaceous-Tertiary mass
      extinction event.
AB  - The fossil record has been used to support the origin and radiation of modern
      birds (Neornithes) in Laurasia after the Cretaceous-Tertiary mass extinction
      event, whereas molecular clocks have suggested a Cretaceous origin for most avian
      orders. These alternative views of neornithine evolution are examined using an
      independent set of evidence, namely phylogenetic relationships and historical
      biogeography. Pylogenetic relationships of basal lineages of neornithines,
      including ratite birds and their allies (Palaleocognathae), galliforms and
      anseriforms (Galloanserae), as well as lineages of the more advanced Neoves
      (Gruiformes, (Capimulgiformes, Passeriformes and others) demonstrate pervasive
      trans-Antarctic distribution patterns. The temporal history of the neornithines
      can be inferred from fossil taxa and the ages of vicariance events, and along
      with their biogeographical patterns, leads to the conclusion that neornithines
      arose in Gondwana prior to the Cretaceous Tertiary extinction event.

PMID- 11296858
TI  - Food-plant niche selection rather than the presence of ant nests explains
      oviposition patterns in the myrmecophilous butterfly genus Maculinea.
AB  - It has been suggested that the socially parasitic butterfly Maculinea alcon
      detects ant odours before ovipositing on initial larval food plants near colonies
      of its obligate ant host Myrmica ruginodis. It has also been suggested that
      overcrowding on food plants near M. ruginodis is avoided by an ability to detect
      high egg loads, resulting in a switch to selecting plants near less suitable ant
      species. If confirmed, this hypothesis (H1) would have serious implications for
      the application of current population models aimed at the conservation of
      endangered Maculinea species, which are based on the null hypothesis (H0) that
      females randomly select food plants whose flower buds are at a precise
      phenological stage, making oviposition independent of ants. If H1 were wrong,
      practical management based upon its assumptions could lead to the extinction of
      protected populations. We present data for the five European species of Maculinea
      which show that (i) each oviposits on a phenologically restricted flower-bud
      stage, which accounts for the apparent host-ant-mediated niche separation in
      sympatric populations of Maculinea nausithous and Maculinea teleius, (ii) there
      is no temporal shift in oviposition by Maculinea arion in relation to host ant
      distribution or egg density, and (iii) oviposition patterns in 13 populations of
      M. alcon's closest relative, Macaulinea rebeli, conform to H0 not H1 predictions.
      It is concluded that conservation measures should continue to be based on H0.

PMID- 11296859
TI  - Association between major histocompatibility complex class IIB alleles and
      resistance to Aeromonas salmonicida in Atlantic salmon.
AB  - We have tested the importance of genetic variation in the major
      histocompatibility complex (MHC) class IIB in Atlantic salmon (Salmo salar) for
      survival after challenge with a highly virulent bacterial pathogen. Forty
      juvenile full siblings from each of 120 families were infected with the bacterium
      Aeromonas salmonicida, which causes high mortality in salmon due to furunculosis.
      Fishes from high-resistance (HR, < 35% mortality) and low-resistance (L,R, > 80%
      mortality) families were screened for their MHC class IIB genotypes using the
      denaturing gradient gel electrophoresis (DGGE) technique. The exon 2 sequences,
      encoding the major part of the peptide-binding region, were established for each
      DGGE fragment. One allele, e, containing a missense single base substitution was
      significantly more prevalent in HR families than in LR families. An odds-ratio
      test showed that broods carrying this allele had a 12-fold higher chance of being
      HR than broods without the e allele. A second allele, i, showed significantly
      higher frequencies in uninfected and surviving individuals than in infected dead
      individuals. A third allele, j, tended to more prevalent both in LR families and
      in individuals that had died of the infection. There was no correlation between
      MHC heterozygosity and resistance to A. salmonicida. Our results support the
      hypothesis that MHC polymorphism is maintained through pathogen-driven selection
      acting by means of frequency-dependent selection rather than heterozygous
      advantage.

PMID- 11296860
TI  - Fat reserves and perceived predation risk in the great tit, Parus major.
AB  - The fat reserves of small birds are built up daily as insurance against
      starvation. They are believed to reflect a trade-off between the risks of
      starvation and predation such that in situations of high predation risk birds are
      expected either to reduce their fat reserves in response to mass-dependent
      predation risk or to increase them in response to foraging interruptions. We
      assessed the effect on fat reserves of experimentally altering the perceived (but
      not the actual) risk of predation of wild great tits at a winter feeding site.
      The perceived predation risk was alternated between 'safe' and 'risky'.
      Increasing the perceived risk of predation involved 'swooping' a model
      sparrowhawk over the feeder at four unpredictable times each day using a remote
      mechanism We produce evidence that the experiment was suceessfull in altering the
      perceived risk of predation. As predicted from the hypothesis of mass-dependent
      predation risk, great tits (Parus major) carried significantly reduced fat
      reserves during the 'risky' treatment. Furthermore, dominant individuals were
      able to reduce their reserves more than subordinates. As birds returned to
      feeders within seconds after a predator 'attack', the reduction in fat reserves
      cannot be attributed to an interruption in feeding.

PMID- 11296861
TI  - High guanine-cytosine content is not an adaptation to high temperature: a
      comparative analysis amongst prokaryotes.
AB  - The causes of the variation between genomes in their guanine (G) and cytosine (C)
      content is one of the central issues in evolutionary genomics. The thermal
      adaptation hypothesis conjectures that, as G:C pairs in DNA are more thermally
      stable than adenonine:thymine pairs, high GC content may he a selective response
      to high temperature. A compilation of data on genomic GC content and optimal
      growth temperature for numerous prokaryotes failed to demonstrate the predicted
      correlation. By contrast, the GC content of Structural RNAs is higher at high
      temperatures. The issue that we address here is whether more freely evolving
      sites in exons (i.e. codonic third positions) evolve in the same manner as
      genomic DNA as a whole, Showing no correlated response, or like structural RNAs
      showing a strong correlation. The latter pattern would provide strong support for
      the thermal adaptation hypothesis, as the variation in GC content between
      orthologous genes is typically most profoundly seen at codon third sites (GC3).
      Simple analysis of completely sequenced prokaryotic genomes shows that GC3, but
      not genomic GC, is higher on average in thermophilic species. This demonstrates,
      if nothing else, that the results from the two measures cannot be presumed to be
      the same. A proper analysis, however, requires phylogenetic control. Here,
      therefore, we report the results of a comparative analysis of GC composition and
      optimal growth temperature for over 100 prokaryotes. Comparative analysis fails
      to show, in either Archea or Eubacteria, any hint of connection between optimal
      growth temperature and GC content in the genome as a whole, in protein-coding
      regions or, more crucially at GC. Conversely, comparable analysis confirms that
      GC content of structural RNA is strongly correlated with optimal temperature.
      Against the expectations of the thermal adaptation hypothesis, within prokaryotes
      GC content in protein-coding genies, even at relatively freely evolving sites,
      cannot be considered an adaptation to the thermal environment.

PMID- 11296862
TI  - How should we define fitness in structured metapopulation models? Including an
      application to the calculation of evolutionarily stable dispersal strategies.
AB  - We define a fitness concept applicable to structured metapopulations consisting
      of infinitely many equally coupled patches. In addition, we introduce a more
      easily calculated quantity Rm that relates to fitness in the same manner as R0
      relates to fitness in ordinary population dynamics: the Rm of a mutant is only
      defined when the resident population dynamics converges to a point equilibrium
      and Rm is larger (smaller) than 1 if and only if mutant fitness is positive
      (negative). Rm corresponds to the average number of newborn dispersers resulting
      from the (on average less than one) local colony founded by a newborn disperser.
      Efficient algorithms for calculating its numerical value are provided. As an
      example of the usefulness of these concepts we calculate the evolutionarily
      stable conditional dispersal strategy for individuals that can account for the
      local population density in their dispersal decisions. Below a threshold density
      x, at which staying and leaving are equality profitable, everybody should stay
      and above x everybody should leave, where profitability is measured as the mean
      number of dispersers produced through lines of descent consisting of non
      dispersers.

PMID- 11296863
TI  - Lateral sensitivity modulation explains the flanker effect in contrast
      discrimination.
AB  - We used a dual-masking paradigm to study how contrast discrimination can be
      influenced by the presence of adjacent stimuli. The task of the observer was to
      detect a target superimposed on a pedestal in the presence of flankers. The
      flankers (i) reduce the target threshold at zero pedestal contrast, (ii) shift
      the target threshold versus pedestal contrast (TvC) function horizontally to the
      left on a log-log plot at high pedestal contrasts, and (iii) reduce the size of
      pedestal facilitation at low pedestal contrasts. The horizontal shift at high
      pedestal contrasts suggests that the flanker effect is a multiplicative factor
      that cannot be explained by previous models of contrast discrimination. We extend
      the divisive inhibition model of contrast discrimination by implementing the
      flanker effect as a lateral multiplicative sensitivity modulation. This extended
      model provides a good account of the data.

PMID- 11296864
TI  - Sexual conflict and the evolution of female mate choice and male social
      dominance.
AB  - Conflicts between the sexes over control of reproduction are thought to lead to a
      cost of sexual selection through the evolution of male traits that manipulate
      female reproductive physiology and behaviour, and female traits that resist this
      manipulation. Although studies have begun to document negative fitness effects of
      sexual conflict, studies showing the expected association between sexual conflict
      and the specific behavioural mechanisms of sexual selection are lacking. Here we
      experimentally manipulated the opportunity for sexual conflict in the cockroach.
      Nauphoeta cinerea and showed that, for this species, odour cues in the social
      environment influence the behavioural strategies and fitness of males and females
      during sexual selection. Females provided with the opportunity for discriminating
      between males but not necessarily mating with preferred males produced fewer male
      offspring than females mated at random. The number of female offspring produced
      was not affected, nor was the viability of the offspring. Experimental
      modification of the composition of the males' pheromone showed that the fecundity
      effects were caused by exposure to the pheromone component that makes males
      attractive to females but also makes males less likely to be dominant. Female
      mate choice therefore carries a demographic cost but functions to avoid male
      manipulation and aggression. Male-male competition appears to function to
      circumvent mate choice rather than directly manipulating females, as the mate
      choice can be cryptic. The dynamic struggle between the sexes for control of
      mating opportunities and outcomes in N. cinerea therefore reveals a unique role
      for sexual conflict in the evolution of the behavioural components of sexual
      selection.

PMID- 11296865
TI  - Resolution of male-female conflict in an hermaphroditic flower.
AB  - The flowers of most angiosperm species are hermaphroditic. Spatial separation of
      male and female organs within a flower (hercogamy) is a common character
      traditionally interpreted as an adaptation to reduce intrafloral self
      fertilization, one potential cost of hermaphroditism. Another possible cost that
      may lead to selection for hercogamy is physical interference between male and
      female floral functions. Here, I present evidence demonstrating the role of a
      floral character in reducing female interference with male function. The bi-lobed
      stigma of the bush monkeyflower closes after receiving pollen, causing increased
      spatial separation of the anthers and stigma ('movement' hercogamy). Experimental
      manipulations show that flowers with closed stigmas export more than twice as
      much pollen to other flowers as those in which the stigma is prevented from
      closing. However, stigma closure only minimally reduces the potential for
      intrafloral self-pollination. This study provides the first experimental evidence
      that selection to reduce intrafloral male female interference can be a strong
      selective force and can drive the evolution of floral characters usually
      interpreted as mechanisms to reduce self-fertilization.

PMID- 11296866
TI  - The evolution of female mate choice by sexual conflict.
AB  - Although empirical evidence has shown that many male traits have evolved via
      sexual selection by female mate choice, our understanding of the adaptive value
      of female mating preferences is still very incomplete. It has recently been
      suggested that female mate choice may result from females evolving resistance
      rather than attraction to males, but this has been disputed. Here, we develop a
      quantitative genetic model showing that sexual conflict over mating indeed
      results in the joint evolution of costly female mate choice and exaggerated male
      traits under a wide range of circumstances. In contrast to tradition explanations
      of costly female mate choice, which rely on indirect genetic benefits, our model
      shows that mate choice can be generated as a side-effect of females evolving to
      reduce the direct costs of mating.

PMID- 11296867
TI  - Prey scan at random to evade observant predators.
AB  - Anti-predator scans by animals occur with very irregular timing, so that the
      initiation of scans resembles a random, Poisson-like, process. At first sight,
      this seems both dangerous (predators could exploit the long intervals) and
      wastefull (scans after very short intervals are relatively uninformative). We
      explored vigilance timing using a new model that allows both predators and prey
      to vary their behaviour. Given predators that attack at random with respect to
      prey behaviour, constant inter-scan intervals minimize predation risk. However,
      if prey scan regularly to minimize their risk from randomly attacking predators,
      they become more vulnerable to predators that initiate attacks when the inter
      scan intervals begin. If, in order to defeat this tactic, prey choose extremely
      variable inter-scan intervals, they become more vulnerable to predators who wait
      for long intervals before launching attacks. Only if predators can monitor the
      variability of inter-scan intervals and either attack immediately (if variability
      is too low) or wait for long intervals to attack (if variability is too high)
      does the empirically observed pattern of Poisson-like scanning become the optimal
      prey strategy.

PMID- 11296869
TI  - Variability of the QRS signal in high-resolution electrocardiograms and
      magnetocardiograms.
AB  - The variability of electric and magnetic signals from the heart during the
      depolarization phase is investigated. A signal processing method is developed,
      which provides estimates for the beat-to-beat variability of the QRS-complex. The
      method is based on the decomposition of the depolarization signal into bandpass
      signals by means of the Morlet wavelet transform. The beat variability of the
      depolarization signal is estimated by normalized variances of the envelope and
      instantaneous frequency of bandpass signals. Time intervals of the bandpass
      filtered depolarization signals having a high signal-to-noise ratio are selected
      applying an analysis based on phase statistics. The method was tested by computer
      simulation and experimental data taken from electrocardiographic and
      magnetocardiographic measurements of healthy persons and patients prone to
      malignant ventricular tachycardia (VT) or ventricular fibrillation (VF). Results
      suggest that the calculated variance parameters permit the characterization of
      beat variable depolarization signals and distinguish VT/VF patients from healthy
      persons.

PMID- 11296868
TI  - Evolution of river dolphins.
AB  - The world's river dolphins (Inia, Pontoporia, Lipotes and Platanista) are among
      the least known and most endangered of all cetaceans. The four extant genera
      inhabit geographically disjunct river systems and exhibit highly modified
      morphologies, leading many cetologists to regard river dolphins as an unnatural
      group. Numerous arrangements have been proposed for their phylogenetic
      relationships to one another and to other odontocete cetaceans. These alternative
      views strongly affect the biogeographical and evolutionary implications raised by
      the important, although limited, fossil record of river dolphins. We present a
      hypothesis of river dolphin relationships based on phylogenetic analysis of three
      mitochondrial genes for 29 cetacean species, concluding that the four genera
      represent three separate, ancient branches in odontocete evolution. Our molecular
      phylogeny corresponds well with the first fossil appearances of the primary
      lineages of modern odontocetes. Integrating relevant events in Tertiary
      palaeoceanography, we develop a scenario for river dolphin evolution during the
      globally high sea levels of the Middle Miocene. We suggest that ancestors of the
      four extant river dolphin lineages colonized the shallow epicontintental seas
      that inundated the Amazon, Parana, Yangtze and Indo-Gangetic river basins,
      subsequently remaining in these extensive waterways during their transition to
      freshwater with the Late Neogene trend of sea-level lowering.

PMID- 11296870
TI  - Analysis and comparison of reflex times and electromyograms of cervical muscles
      under impact loading using surface and fine-wire electroces.
AB  - Myoelectric signals [electromyograms (EMGs)] can be collected using either
      surface or fine-wire electrodes. Application of the latter results in higher
      frequency contents of EMG. In the field of impact biomechanics, surface
      electrodes are more often utilized than fine-wire ones. However, the removal of
      motion artefacts from EMG recorded under transient loads requires application of
      high-pass filters with relatively high cutoff frequencies, which may eliminate a
      significant part of the surface EMG power spectra. Therefore, in the current
      study, both surface and fine-wire electrodes were utilized to record the EMG of
      cervical muscles under conditions simulating a rear-end car collision at low
      speed. The results indicated that application of high-pass filtering at 50 Hz can
      be necessary to remove motion artefacts from the EMG collected under such
      conditions. Such filtering resulted in a higher decrease in amplitude of the
      surface EMG than that of the fine-wire one. However, the reflex times obtained
      here were not significantly affected by the type of the electrodes utilized to
      collect EMG.

PMID- 11296871
TI  - An automatic sequential recognition method for cortical auditory evoked
      potentials.
AB  - The detection of cortical auditory evoked potentials (CAEP), which are part of
      the electroencephalogram (EEG) in reaction to acoustic stimuli, has important
      applications such as determining objective audiograms. The detection is usually
      performed by a human operator, with support from often basic signal processing
      methods. This paper presents a novel mechanism for the detection of CAEPs, which
      is fully automatic and stops the measurement when a given confidence is reached.
      This proposed detector comprises of three stages. First, a feature extraction by
      a wavelet transform parameterizes the time domain EEG signal by only few
      transform coefficients. This feature vector is then classified by a neural
      network which yields a binary vote on every EEG segment. Finally, a sequential
      statistical test is performed on successive classifications; this stops the
      measurement if a specified decision confidence has been reached. The adjustment
      of the detector according to a clinical database is discussed. Thus adjusted, the
      proposed CAEP detection scheme is applied to a study, and compared with a human
      operator. The results demonstrate that this method can attain similar results,
      but outperforms the human expert for stimulation levels close to the hearing
      threshold.

PMID- 11296872
TI  - Selectivity of multiple-contact nerve cuff electrodes: a simulation analysis.
AB  - Advances in functional neuromuscular stimulation (FNS) have increased the need
      for nerve cuff designs that can control multiple motor functions through
      selective stimulation of selected populations of axons. This selectivity has
      proved to be difficult to achieve. Recent experiments suggest that it is possible
      to slowly reshape peripheral nerve without affecting its physiological function.
      Using computer simulations we have tested the hypothesis that changing the cross
      section of a nerve from a round to a flat configuration can significantly improve
      the selectivity of a nerve cuff. We introduce a new index to estimate selectivity
      to evaluate the various designs. This index is based on the ability of a nerve
      electrode to stimulate a target axon without stimulating any other axons. The
      calculations involve a three-dimensional finite element model to represent the
      electrical properties of the nerve and cuff and the determination of the firing
      properties of individual axons. The selectivity rating was found to be
      significantly higher for the Flat Cuff than the Round Cuff. The result was valid
      with uniform or random distribution of axons and with a random distribution of
      fascicles diameters. Flattening of individual fascicles also improved the
      selectivity of the Flat Cuff but only when the number of contacts used was
      increased to maintain uniform contact density. Therefore, cuff designs that can
      reshape the nerve into flatter configurations should yield better cuff
      performance than the cylindrical cuffs but will require higher contact density.

PMID- 11296873
TI  - Analysis of a linear model for electrical stimulation of axons--critical remarks
      on the "activating function concept".
AB  - A comprehensive description of a linear model of an axon of infinite length
      exposed to an external voltage is presented. The steady-state transmembrane
      potential is derived as a function proportional to the convolution product of the
      second spatial difference sn of the external potential (the "activating
      function") and the impulse response psin of a spatial low-pass filter. The
      impulse response psin represents the influence of the axon and is fully
      characterized by the axon's length constant lambda. A closed-form solution of the
      cable equation can be given in the spatial Fourier domain. Due to a "spectral
      acceleration effect", the overall transmembrane potential approximates the steady
      state considerably faster than an exponential with the axon's membrane time
      constant tau. The effect is increasingly pronounced, the smaller the distance
      between the electrode and the axon. Regarding myelinated fibers and practically
      relevant electrode/axon distances and pulse widths, the transmembrane potential
      at the end of a stimulation pulse can be substantially better approximated by the
      steady-state condition than by the initial response as claimed by the "activating
      function concept." Quantitative limits for the range of validity of the
      activating function concept are derived.

PMID- 11296876
TI  - Improving PET-based physiological quantification through methods of wavelet
      denoising.
AB  - The goal of this study was to evaluate methods of multidimensional wavelet
      denoising on restoring the fidelity of biological signals hidden within dynamic
      positron emission tomography (PET) images. A reduction of noise within pixels,
      between adjacent regions, and time-serial frames was achieved via redundant
      multiscale representations. In analyzing dynamic PET data of healthy volunteers,
      a multiscale method improved the estimate-to-error ratio of flows fivefold
      without loss of detail. This technique also maintained accuracy of flow estimates
      in comparison with the "gold standard," using dynamic PET with O15-water. In
      addition, in studies of coronary disease patients, flow patterns were preserved
      and infarcted regions were well differentiated from normal regions. The results
      show that a wavelet-based noise-suppression method produced reliable
      approximations of salient underlying signals and led to an accurate
      quantification of myocardial perfusion. The described protocol can be generalized
      to other temporal biomedical imaging modalities including functional magnetic
      resonance imaging and ultrasound.

PMID- 11296875
TI  - Guidelines for predicting lesion size at common endocardial locations during
      radio-frequency ablation.
AB  - We used the finite element method to study the effect of radio-frequency (RF)
      catheter ablation on tissue heating and lesion formation at different
      intracardiac sites exposed to different regional blood velocities. We examined
      the effect of application of RF current in temperature- and power-controlled mode
      above and beneath the mitral valve annulus where the regional blood velocities
      are high and low respectively. We found that for temperature-controlled ablation,
      more power was delivered to maintain the preset tip temperature at sites of high
      local blood velocity than at sites of low local blood velocity. This induced more
      tissue heating and larger lesion volumes than ablations at low velocity regions.
      In contrast, for power-controlled ablation, tissue heating was less at sites of
      high compared with low local blood velocity for the same RF power setting. This
      resulted in smaller lesion volumes at sites of low local velocity. Our numerical
      analyzes showed that during temperature-controlled ablation at 60 degrees C, the
      lesion volumes at sites above and underneath the mitral valve were comparable
      when the duration of RF current application was 10 s. When the duration of RF
      application was extended to 60 s and 120 s, lesion volumes were 33.3% and 49.4%
      larger above the mitral valve than underneath the mitral valve. Also, with
      temperature-controlled ablation, tip temperature settings of 70 degrees C or
      greater were associated with a risk of tissue overheating during long ablations
      at high local blood velocity sites. In power-controlled ablation (20 W), the
      lesion volume formed underneath the mitral valve was 165.7% larger than the
      lesion volume above the mitral valve after 10 s of ablation. We summarized the
      guidelines for energy application at low and high flow regions.

PMID- 11296874
TI  - Simulation of dynamic bubble spectra in tissues.
AB  - Decompression sickness (DCS) is the result of bubble formation in the body due to
      excessive/rapid reduction in the ambient pressure. Existing models relate the
      decompression stress either to the inert gas load or to the size of a single
      bubble in a tissue compartment. This paper presents a model that uses the gas
      exchange equations combined with bubble dissolution physics and population
      balance equations to produce a new mathematical framework for DCS modeling. This
      framework, the population balance model for decompression sickness (PBMDS),
      simulates the number of bubbles with their corresponding size distributions in a
      compartmental tissue array. The model has a modular structure that enables one to
      explore different modeling results with respect to key aspects of DCS, such as
      gas exchange, nucleation, and surface tension. The paper's goal is to present the
      derivation of PBMDS in detail, however, three simple application case studies are
      provided. The aim of these case studies is to suggest that PBMDS supplies
      additional information on bubble distribution while supporting the results from
      current practice.

PMID- 11296877
TI  - Wavelet transform filtering and nonlinear anisotropic diffusion assessed for
      signal reconstruction performance on multidimensional biomedical data.
AB  - Computer tomography (CT) techniques are the most widely applicable noninvasive
      methods for obtaining two- and three-dimensional insights into biological
      objects. They comprise CT for medical applications, as well as electron
      tomography used for investigating macromolecular and cellular specimens. Recent
      advances in the recording schemes improve the speed and resolution frontiers and
      provide new insights into structural organizations of different objects. However,
      many data sets suffer from a poor signal-to-noise ratio, which severely hinders
      the application of methods for automated data analysis, such as feature
      extraction, segmentation, and visualization. We propose the multidimensional
      implementation of two powerful signal reconstruction techniques, namely invariant
      wavelet filtering and nonlinear anisotropic diffusion. We establish quantitative
      measures to assess the signal reconstruction performance on synthetic data and
      biomedical images. The appropriate multidimensional implementations of wavelet
      and diffusion techniques allow for a superior performance over conventional noise
      reduction methods. We derive the conditions for the choice between wavelet and
      diffusion techniques with respect to an optimal signal reconstruction
      performance. Results of applying the proposed methods in two very different
      imaging domains-molecular biology and clinical research-are provided.

PMID- 11296878
TI  - A noninvasive cross-correlation ultrasound technique for detecting spatial
      profile of laser-induced coagulation damage--an in vitro study.
AB  - A cross-correlation A-mode ultrasound technique is proposed for noninvasively
      detecting the spatial profile of coagulation damage in tissue being irradiated by
      laser. The basic assumption underlying this technique is that when coagulation is
      taking place in a tissue region, owing to thermally-induced structure changes in
      tissue, the waveform of echo signal scattered from that region should be changing
      accordingly. Our technique consists of four steps: 1) repeatedly sending the same
      acoustic signal to the tissue being heated; 2) tracking echo signals scattered
      from many small tissue regions using a cross-correlation echo-tracking technique;
      3) quantifying waveform change of echo signal scattered from each region by means
      of cross-correlation coefficient between the currently acquired signal and a
      reference signal; 4) using the spatial profile of the degree of the waveform
      change to represent the tissue coagulation status at different depths. We carried
      out 23 heating experiments on fresh canine liver samples using a Nd:YAG laser
      (1,064 nm wavelength) at various light intensity (62 to 105 W/cm2) and exposure
      time (20 to 350 s). A 13-mm-diameter 10-MHz broadband single-element spherical
      focused ultrasound transducer was used. The spatial profiles of the degree of
      coagulation damage in the heated tissues, as determined by our technique,
      qualitatively agreed with the grossly inspected results. They also appeared to be
      consistent with the experimental and theoretical findings in the literature on
      laser-tissue interaction. Moreover, we developed an automatic procedure to
      compute the coagulation depth using the spatial profiles of the waveform change.
      We used the result as an indirect but quantitative means for evaluating the
      technique. Good overall agreement with a root mean square (rms) difference of
      only 0.81 mm was obtained between the computed and visually inspected final
      coagulation depths for the 23 experiments.

PMID- 11296880
TI  - An in vivo analysis of the motion of the peri-talar joint complex based on MR
      imaging.
AB  - The purpose of this work is to characterize the three-dimensional (3-D) motion of
      the peritalar joint complex in vivo using magnetic resonance imaging (MRI). Each
      image data set utilized in this study is made of 60 longitudinal MR slices of the
      foot in each of eight positions from extreme pronation to extreme supination. We
      acquired and analyzed ten such data sets from normal subjects, seven data sets
      from pathological joints and two postoperative data sets. We segmented and formed
      the surfaces of the calcaneus, talus, cuboid and navicular from all data sets.
      About 30 geometrical parameters are computed for each joint in each position. The
      results present features of normal motion and show how normal and abnormal motion
      can be distinguished. They also show the consequences of surgery on the motion.
      This non- invasive method offers a unique tool to characterize and quantify the 3
      D motion of the rearfoot in vivo from MR images.

PMID- 11296881
TI  - CMOS neurostimulation ASIC with 100 channels, scaleable output, and bidirectional
      radio-frequency telemetry.
AB  - 100-channel neurostimulation circuit comprising a complementary metal oxide
      semiconductor (CMOS), application-specific integrated circuit (ASIC) has been
      designed, constructed and tested. The ASIC forms a significant milestone and an
      integral component of a 100-electrode neurostimulation system being developed by
      the authors. The system comprises an externally worn transmitter and a body
      implantable stimulator. The purpose of the system is to communicate both data and
      power across tissue via radio-frequency (RF) telemetry such that externally
      programmable, constant current, charge balanced, biphasic stimuli may be
      delivered to neural tissue at 100 unique sites. An intrinsic reverse telemetry
      feature of the ASIC has been designed such that information pertaining to the
      device function, reconstruction of the stimulation voltage waveform, and the
      measurement of impedance may be obtained through noninvasive means. To compensate
      for the paucity of data pertaining to the stimulation thresholds necessary in
      evoking a physiological response, the ASIC has been designed with scaleable
      current output. The ASIC has been designed primarily as a treatment of
      degenerative disorders of the retina whereby the 100 channels are to be utilized
      in the delivery of a pattern of stimuli of varying intensity and or duty cycle to
      the surviving neural tissue of the retina. However, it is conceivable that other
      fields of neurostimulation such as cochlear prosthetics and functional electronic
      stimulation may benefit from the employment of the system.

PMID- 11296879
TI  - An image reconstruction algorithm for three-dimensional electrical impedance
      tomography.
AB  - Electrical impedance tomography (EIT) has been studied by many authors and in
      most of this work it has been considered to be a two-dimensional problem. Many
      groups are now turning their attention to the full three-dimensional case in
      which the computational demands become much greater. It is interesting to look
      for ways to reduce this demand and in this paper we describe an implementation of
      an algorithm that is able to achieve this by precomputing many of the quantities
      needed in the image reconstruction. The algorithm is based on a method called
      NOSER introduced some years ago by Cheney et al. [3]. In this paper we have
      significantly extended the method by introducing a more realistic electrode model
      into the analysis. We have given explicit formulae for the quantities involved so
      that the reader can reproduce our results.

PMID- 11296882
TI  - Measurement of directional thermal properties of biomaterials.
AB  - This paper presents an experimental technique to measure the directional thermal
      conductivity and thermal diffusivity of materials. A heated thermistor heats the
      sample and a sensing thermistor placed about 2.5 mm away measures the temperature
      rise due the heating pulse at the heated thermistor. An empirical relation
      between the power delivered by the first thermistor and the temperature rise
      recorded by the sensing thermistor is used to measure the thermal conductivity of
      the material along the line joining the thermistors. Diffusivity of the material
      is determined from the delay between the power pulse in the heated thermistor and
      the temperature pulse at the sensing thermistor. Signal processing was done to
      eliminate errors in the measurement due to change of base line temperature.
      Uncertainty of the measurement technique was found to be 5% when tested in media
      of known thermal properties. The thermal conductivity and thermal diffusivity of
      swine left ventricle in normal and ablated conditions were measured using this
      technique. The thermal conductivity of the tissue dropped significantly from 0.61
      to 0.50 W.m(-1).K(-1) after ablation while the diffusivity dropped from 2.1 x 10(
      7) to 1.7 x 10(-7)m2.s(-1).

PMID- 11296883
TI  - A device to apply user-specified strains to biomaterials in culture.
AB  - An apparatus was developed to apply user-specified displacements to biomaterial
      samples in culture. The device allowed cyclic waveforms of bandwidth 0 Hz to 20
      Hz to be applied under physiologic thermal (37.5 degrees C) and [CO2] (5%)
      conditions. For a 0 Hz to 20 Hz bandwidth signal similar in shape to a
      ventricular pressure waveform, the mean displacement error was 0.26% of the full
      scale output. The maximum overshoot was 0.700%. Environmental system evaluation
      tests demonstrated a specimen cartridge temperature of 37.20 +/- 0.15 degrees C
      during cyclic loading and 37.23 +/- 0.21 degrees C during static conditions.
      [CO2] was 5.29 +/- 0.54% during cyclic loading and 5.25 +/- 0.61% during static
      conditions. Laminar flow applied at the loading rod entrances to the specimen
      cartridge ensured the sample remained sterile during testing. As a preliminary
      evaluation, polyurethane samples were seeded with fetal foreskin fibroblasts and
      subject to intermittent cyclic displacements. Results demonstrated enhanced cell
      proliferation and increased [PGE2] for samples subjected to 10% strain compared
      with unstrained controls. A next step will be to evaluate cell response
      sensitivity to strain magnitude, duration, direction, and frequency. The long
      term intent is to establish mechanical loading configurations that induce
      acceptable or adaptation-inducing responses for use in implant design and tissue
      engineering applications.

PMID- 11296884
TI  - Saliva testing after single and chronic administration of dihydrocodeine.
AB  - In the present study, concentrations of dihydrocodeine and its metabolites in
      saliva and serum were compared after single low-dose and chronic high-dosage
      administration of the drug. In the first investigation, blood and saliva were
      collected periodically from six subjects after oral administration of 60 mg
      dihydrocodeine. In the second study, 20 subjects on oral dihydrocodeine
      maintenance provided single samples of blood and saliva simultaneously. Serum
      protein binding of salivary analytes and their recovery from the adsorbing
      material of the collection device as well as pH values of saliva samples were
      determined. The fluids were analyzed for dihydrocodeine and the major metabolites
      by high-performance liquid chromatography. In the single dose study
      dihydrocodeine was the only analyte found in saliva for up to 12-24 h post-dose.
      The half-life of dihydrocodeine in saliva was about twice that found in blood.
      The ratios of saliva/serum concentrations ranged from 1.2 to 17.0. After chronic
      high-dosage use, dihydrocodeine was the main salivary analyte and N
      nordihydrocodeine was present in a few samples. Saliva/serum concentration ratios
      of dihydrocodeine were strongly dependent on the pH value of saliva and, to a
      lesser extent, on serum-protein binding. The saliva/serum ratios were more
      similar after chronic administration. The data suggest a passive diffusion
      process as the underlying mechanism for the transport of dihydrocodeine into
      saliva. After both single and chronic use, the presence of the drug in saliva can
      be used as evidence of recent substance administration.

PMID- 11296885
TI  - DNA analyses of the remains of the Prince Branciforte Barresi family.
AB  - The five skeletons found buried in the church of Militello di Catania, Sicily,
      were tentatively identified by morphological analysis and historical reports as
      the remains of Prince Branciforte Barresi, two of his children, his brother and
      another juvenile member of the family (sixteenth and seventeenth centuries). In
      order to attempt to clarify the degree of relationships of the five skeletons,
      sex testing and mitochondrial DNA (mtDNA) sequence analysis of the hypervariable
      segments I and II (HV1 and HV2) of control region were performed. Moreover, the 9
      bp-deletion marker of region V (COII/tRNAlys) was examined. Molecular genetic
      analyses were consistent with historical expectations, although they did not
      directly demonstrate that these are in fact the remains of the Prince and his
      relatives, due to the impossibility of obtaining DNA from living maternal
      relatives of the Prince.

PMID- 11296886
TI  - Statistical analyses to support forensic interpretation for a new ten-locus STR
      profiling system.
AB  - A new ten-locus STR (short tandem repeat) profiling system was recently
      introduced into casework by the Forensic Science Service (FSS) and statistical
      analyses are described here based on data collected using this new system for the
      three major racial groups of the UK: Caucasian. Afro-Caribbean and Asian (of Indo
      Pakistani descent). Allele distributions are compared and the FSS position with
      regard to routine significance testing of DNA frequency databases is discussed.
      An investigation of match probability calculations is carried out and the
      consequent analyses are shown to provide support for proposed changes in how the
      FSS reports DNA results when very small match probabilities are involved.

PMID- 11296887
TI  - An initial study on the succession of sarcosaprophagous Diptera (Insecta) on
      carrion in the southeastern Iberian peninsula.
AB  - We present the results of the first study concerning Diptera carried out on the
      sarcosaprophagous fauna of southeastern Spain. This work represents the first
      attempt to describe dipteran sarcosaprophagous fauna in the Iberian peninsula,
      the seasonal succession, main features of the population dynamics and the main
      taxa useful for estimation of the post-mortem interval. The results of this study
      could be very useful for further forensic case work in the west Mediterranean
      area.

PMID- 11296888
TI  - Cerebral cast angiography as an aid to medicolegal autopsies in cases of death
      after adult cardiac surgery.
AB  - Due to an increase in age of the patient population in cardiac surgery, cerebral
      complications are increasing in frequency, also as a cause of death. In order to
      reveal cerebral pathology associated with a fatal outcome after cardiac surgery,
      we re-evaluated the cast angiographs and medico-legal autopsy documents of 144
      adult cardiac surgery subjects over a 7-year period. Special attention was paid
      to the ability of post-mortem cast angiography to aid in diagnosing cerebral
      pathology. The autopsy detected new ischemic cerebral lesions in 29 (20%) cases,
      of which 22 (15.3%) were recent infarcts, and 7 were cases of anoxic brain
      damage. Of the recent cerebral infarcts, 12 were associated with cerebral artery
      thrombosis, 4 showed multiple lesions, and the remaining 6 were small single
      infarcts. In addition, one subject had an intracerebral hemorrhage and 72 (50%)
      cerebral edema. By cast angiography, the leakage of contrast medium in the case
      of intracerebral hemorrhage and stenoses of intracranial and cervical arteries
      could be well demonstrated and also revealed 17 (77%) of the 22 recent cerebral
      infarcts. It was found to be suitable for detecting recent brain infarcts
      associated with main cerebral artery thrombosis, with a sensitivity of 92% (11
      out of 12 cases), but was less sensitive in showing small recent infarcts with a
      sensitivity of 60% (6 out of 10 cases) and inferior for the older ones where none
      of the 6 cases were detected. Filling defects caused by cerebral edema were
      difficult to differentiate from technical errors and were encountered in 7 (4.8%)
      cases. A significant predictor for the 29 recent ischemic brain lesions was
      perioperative hypotension. The immediate cause of death was most often of cardiac
      (83%) and cerebral (14%) origin. In 14 cases, cerebral damage was considered to
      be an additional cause of death. The use of cerebral post-mortem cast angiography
      should be recommended, especially for its excellent ability to visualize
      intravascular pathology such as arterial stenoses and thromboses, with a 92%
      sensitivity in showing new main cerebral artery thromboses, before likely
      distortion of the vascular anatomy by dissection.

PMID- 11296889
TI  - The results of an mtDNA study of 1,200 inhabitants of a German village in
      comparison to other Caucasian databases and its relevance for forensic casework.
AB  - Mitochondrial DNA control region sequences were determined in 1,200 male
      volunteers from one village area of Lower Saxony for the hypervariable region 1
      (HV1). The 154 variable positions found resulted in 460 different haplotypes with
      a haplotype diversity value of 0.98165. The number of different haplotypes showed
      a nearly linear increase with the number of individuals typed. The haplotype
      diversity approached saturation level at a value of approximately 0.981 after
      typing 400 individuals. Furthermore, the number of different haplotypes and the
      haplotype diversity were calculated for four short amplicons of HV1 in order to
      establish the most variable section with a high efficiency for forensic casework.

PMID- 11296890
TI  - The evidential value of STRs. An analysis of exclusion cases.
AB  - In this study, a total of 191 cases with STR exclusions out of 591 paternity
      cases were analysed using 2 STR sets, i.e. (set a) 5 STRs in 462 cases with 150
      exclusions and (set b) 9 STRs in 129 cases with 41 exclusions. Set (a) was
      associated with four exclusions on average while set (b) showed five exclusionary
      loci on average. Double exclusions were observed in 18 cases and further
      elaborated. Of these, 2 ended up with probabilities of paternity of 0.1% and
      0.4%, respectively and with a random occurrence of the hypothesis "mutation" of
      1:20,000 and 1:50,000, respectively, while all other cases were associated with
      much lower frequencies. The conclusion is that the evidential value of a set of
      highly polymorphic STRs applied in paternity cases is usually extremely high.

PMID- 11296891
TI  - Parentage testing with 14 STR loci and population data for 5 STRs in the
      Slovenian population.
AB  - In order to apply a set of 14 short tandem repeat (STR) loci in parentage
      testing, we performed a population genetic study on a sample of 260 unrelated
      people from the Slovenian population. Genotypes for the 14 STRs were determined
      using three multiplex polymerase chain reactions (PCR) and automated fluorescent
      detection. The allele frequencies of the STR loci D5S818, D13S317, D7S820,
      D8S1179 and D18S51 showed no deviation from the Hardy-Weinberg equilibrium and
      agreed well with other Caucasian populations. We resolved a series of 181
      parentage disputes of which 29 were exclusions. In all cases, evidence for
      exclusion was obtained by at least 4 informative STRs out of the 14 loci
      analysed. The 14 loci combined comprise a highly discriminating test suitable for
      paternity and identity testing in the Slovenian population, with an average
      estimated mutation rate of 1.2x10(-3), a combined calculated power of exclusion
      of 99.99974% and paternity index (PI) value of >10(6) in 72% of the inclusion
      cases and >10(5) in 91% of the inclusion cases.

PMID- 11296892
TI  - Fatal intoxication with a decalcifying agent containing formic acid.
AB  - A fatality caused by ingestion of a decalcifying agent containing formic acid is
      reported. Quantitative analysis of formic acid in the form of its methyl ester
      was performed in different body fluids and organ samples using head-space gas
      chromatography with flame ionization detection. The blood taken at the time of
      admission to hospital had a concentration of 370.3 microg/ml, which declined to
      13.9 microg/ml after 6.5 h of haemodialysis. Post-mortem concentrations were
      855.4 microg/ml (heart blood), 2,712 microg/ml (gastric contents), 1128 microg/ml
      (haemorrhagic fluid from abdominal cavity), 3,051 microg/ml (bile), 2,664
      microg/ml (contents of small intestine), 442.7 microg/g (liver) and 542.3
      microg/g (kidney). The most important morphological findings for differentiating
      between oral and respiratory ingestion were ulceration of the oropharynx and the
      oesophagus as well as extensive necrotic lesions in the stomach and the duodenum
      without perforation. Death was caused by massive acidosis, haemolysis, bleeding
      complications, hepatic and renal failure. Toxicological and morphological
      findings revealed that a considerable amount of formic acid had been ingested
      orally with a suicidal intention.

PMID- 11296893
TI  - Heteroplasmy in mtDNA and the weight of evidence in forensic mtDNA analysis: a
      case report.
AB  - Mitochondrial DNA (mtDNA) sequencing has been validated as a useful tool for
      forensic analysis. However, there are several aspects of the analysis which need
      to be considered in order to evaluate the value of the evidence. One of these
      aspects is related to heteroplasmy which is the state when two or more mtDNA
      populations occur in a single individual, cell or mitochondrion. In this report a
      case is described where the mtDNA profile of the blood sample of a raped woman
      was compared with the mtDNA profile of a single hair found in the suspect's car.
      The results obtained show differences in sequence between different portions of
      the hair and the victim's sequence. These differences are related to various
      heteroplasmy events. The concordance between the hair sample and the potential
      source (victim) of this sample is questionable and the strength of the evidence
      depends on how the sequence information is interpreted by the expert. The
      discussion of the results emphasises the necessity to evaluate heteroplasmic
      events in routine forensic work.

PMID- 11296894
TI  - Fatal neglect of the elderly.
AB  - Maltreatment of the elderly is a common problem that affects more than 3% of the
      elderly. We report on two cases of fatal neglect. Risk factors of victims and
      caregivers were analysed in the context of the social history. In both cases, the
      victims had a dominant personality and the abusers (the sons) had been strictly
      controlled and formed by the parent. The victims showed typical risk factors such
      as living together with the abuser, isolation, dependence on care, income and
      money administration. Initially, the victims declined help from outside and self
      neglect occurred. The unemployed perpetrators lived in social isolation and
      depended financially and mentally on the victims. In both cases no mental illness
      was present but there was a decrease of social competence. Legal medicine is
      predominantly involved in fatal cases in connection with external post-mortem
      examinations and autopsies. Also in the living, the medico-legal expert can
      assist in the identification of findings in elderly persons in cases of suspected
      abuse.

PMID- 11296895
TI  - Identification of the skeletal remains of Martin Bormann by mtDNA analysis.
AB  - Contrary to statements of an eye-witness who reported that Martin Bormann, the
      second most powerful man in the Third Reich, died on 2 May 1945 in Berlin,
      rumours persisted over the years that he had escaped from Germany after World War
      II. In 1972, skeletal remains were found during construction work, and by
      investigating the teeth and the bones experts concluded that they were from
      Bormann. Nevertheless, new rumours arose and in order to end this speculation we
      were commissioned to identify the skeletal remains by mitochondrial DNA analysis.
      The comparison of the sequence of HV1 and HV2 from the skeletal remains and a
      living maternal relative of Martin Bormann revealed no differences and this
      sequence was not found in 1,500 Caucasoid reference sequences. Based on this
      investigation, we support the hypothesis that the skeletal remains are those of
      Martin Bormann.

PMID- 11296915
TI  - The state of the art of dynamic coatings.
AB  - The present review highlights the mechanisms of action and efficiency of three
      major classes of dynamic coatings so far adopted in capillary electrophoresis:
      (i) amines to oligo-amines, (ii) neutral synthetic and natural polymers, and
      (iii) neutral and zwitter-ionic surfactants. Their merits and efficacy have been
      explored in depth via a novel quantitation technique consisting of eluting, by
      frontal analysis, any adsorbed proteinaceous material, which can then be
      correctly quantified as a peak as it moves in front of the detector window. This
      is achieved by loading sodium dodecyl sulfate (SDS) micelles onto the cathodic
      side and migrating them electrophoretically into the capillary lumen, where they
      efficiently sweep any adsorbed polypeptide material. It is found that a common
      trend, for all quenchers, is linked to a hydrophobicity scale: the more
      hydrophobic the inhibitor, the better it minimizes potential interactions of
      macromolecules with the wall. This seems to be true for all the classes of
      dynamic modifiers tested. Finally, we describe a novel, dynamic to static
      quencher: it is a quaternary piperazine, bearing a reactive iodine atom at the
      end of a butyl tail (N(methyl-N-omega-iodo-butyl),N'-methyl piperazine). This
      molecule first binds to the wall, at alkaline pH values, via ionic and hydrogen
      bonds. Once docked onto the wall, the reactive tail forms a covalent link with
      the silica surface, to which it then remains permanently affixed.

PMID- 11296916
TI  - Stationary phases for capillary electrophoresis and capillary
      electrochromatography.
AB  - An overview of the most recent developments in column technology employed in
      capillary electrophoresis (CE) and capillary electrochromatography (CEC), mainly
      for the separation of small molecules and ions, is presented. Particular emphasis
      is laid on permanent coating. The wall modification methods in CE include
      covalent modification, adsorbed coatings and polymeric coatings, while those in
      CEC include packed columns, open-tubular columns and fritless columns. A short
      discussion on the characterization and selectivity of the bonded phases is also
      given.

PMID- 11296917
TI  - Principles of DNA separation with capillary electrophoresis.
AB  - During the last decade, capillary electrophoresis (CE) of DNA has undergone rapid
      development. This improvement was especially important for DNA sequencing, where
      CE has now become a standard method facilitating to decipher several genomes
      within a very short time. Here, we give a review of the fundamentals of DNA
      separation in CE and the major factors influencing the performance.

PMID- 11296918
TI  - Polymer wall coatings for capillary electrophoresis.
AB  - This review article describes the preparation of dynamic and static polymeric
      wall coatings for capillary electrophoresis. Properties of bare fused-silica
      surfaces and methods for the characterization of capillary coatings are
      summarized. The preparation and basic properties of neutral and charged wall
      coatings are considered. Finally, advantages and potential applications of
      various coatings are discussed.

PMID- 11296919
TI  - Rapid capillary coating by epoxy-poly-(dimethylacrylamide): performance in
      capillary zone electrophoresis of protein and polystyrene carboxylate.
AB  - A fast and simple method for the internal coating of capillaries in capillary
      zone electrophoresis (CZE) is that with epoxy-poly(dimethylacrylamide) (EPDMA).
      Duration of coating by that method is 30 min, compared with that of 24 h when
      using uncross-linked polyacrylamide (PA) under otherwise identical conditions.
      Under the conditions used for the CZE of proteins (pH 9.0, 2% polyethylene
      glycol), the capillary coating with EPDMA is stable for at least 50 consecutive
      runs as judged by the constancy of low electroosmotic flow, equalling the
      stability of coating achieved by PA. Protein mobilities and protein peak
      asymmetry (suggestive of reversible interaction with the capillary wall) are also
      found to be the same in EPDMA and PA coated capillaries. Differences between
      EPDMA and PA coating also exist: The former is unstable upon lowering the ionic
      strength of the buffer to 0.003, upon the addition of sodium dodecyl sulfate
      (SDS) to the buffer and in application to the hydrophobic analyte, polystyrene
      carboxylate.

PMID- 11296920
TI  - Wall deactivation with fluorosurfactants for capillary electrophoretic analysis
      of biomolecules.
AB  - This paper describes the use of fluorosurfactants as buffer additives for
      capillary electrophoretic separation of proteins and peptides. Due to
      fluorosurfactant bilayer formation at the capillary inner wall, the surface
      charge can be adjusted and even reversed. If the running buffer pH is kept at a
      level where the proteins have the same sign of charge as the wall, electrostatic
      repulsion will be obtained. The protein wall adsorption can therefore be reduced
      and the separation performance can be noticeably increased. The separation
      performance can also be further improved by including mixtures of different types
      of fluorosurfactants in the running buffer. The buffer system can accordingly be
      adapted for a certain separation problem. Mechanisms for the use of
      fluorosurfactants for wall deactivation in capillary electrophoretic protein
      separations is discussed in the present work and some examples of applications
      are also presented.

PMID- 11296921
TI  - Directed control of electroosmotic flow in nonaqueous electrolytes using
      poly(ethylene glycol) coated capillaries.
AB  - Poly(ethylene glycol) (PEG)-coated capillaries exhibit unique properties in
      nonaqueous electrolytes. Immobilized PEG interacts significantly with different
      cations present in nonaqueous electrolytes. This can induce a positive surface
      charge on PEG-coated capillaries and results in an adjustable anodic
      electroosmotic flow (EOF) in nonaqueous electrolytes whereas a reduced cathodic
      EOF is observed in aqueous electrolytes. The EOF can reversibly be adjusted by
      the variation of the electrolyte constitution, namely the type of the solvent
      used and the nature and concentration of background cations. In methanol and
      especially in acetonitrile electrolytes the magnitude and also the direction of
      EOF is strongly dependent on the water content. Using different alkali metal
      cations, the EOF can be increased, reduced, or even reversed depending on the
      nature of the cation. The directed manipulation of EOF in methanolic electrolytes
      using PEG-coated capillaries was applied for optimization of nonaqueous capillary
      electrophoretic separations of acidic compounds with regard to reproducibility,
      resolution, and analysis time.

PMID- 11296922
TI  - An exactly solvable Ogston model of gel electrophoresis. VI. Towards a theory for
      macromolecules.
AB  - In this article, we present a generalized version of our lattice model of low
      field gel electrophoresis that allows us to treat the case of macromolecules such
      as short linear or circular oligomers and semi-flexible rods. We show that free
      solution electrophoresis problems can be seen as random walks in the
      conformational space of the analyte. For sufficiently small molecules, our
      mathematical approach provides exact mobilities. In a quenched gel-like
      environment, however, both conformational and positional degrees of freedom must
      be used, but exact solutions can also be obtained. As an example, we then
      investigate several two-dimensional model gels, as well as a simple channel
      system where we see evidence of entropic effects that cannot be captured by the
      traditional Ogston concept of free volume.

PMID- 11296923
TI  - On the use of the activation energy concept to investigate analyte and network
      deformations in entangled polymer solution capillary electrophoresis of synthetic
      polyelectrolytes.
AB  - The activation energy associated with the electrophoretic migration of an analyte
      under given electrolyte conditions can be accessed through the determination of
      the analyte electrophoretic mobility at various temperatures. In the case of the
      electrophoretic separation of polyelectrolytes in the presence of an entangled
      polymer network, activation energy can be regarded as the energy needed by the
      analyte to overcome the obstacles created by the separating network. Any
      deformation undergone by the analyte or the network is expected to induce a
      decrease in the activation energy. In this work, the electrophoretic mobilities
      of poly(styrenesulfonates) (PSSs) of various molecular weights (Mr 16 x 10(3) to
      990 x 10(3)) were determined in entangled polyethylene oxide (PEO) solutions as a
      function of temperature (in the 17-60 degrees C range) and the PSS activation
      energies were calculated. The influences of the PSS molecular weight, blob sizes
      zetab of the separating network (related to the PEO concentration), ionic
      strength of the electrolyte and electric field strength (75-600 V/cm) were
      investigated. The results were interpreted in terms of analyte and network
      deformations and were confronted with those previously obtained for DNA migration
      in polymer solutions and chemical gels. For a radius of gyration Rg<zetab the
      activation energy increases with the PSS molecular mass, while the reverse is
      true for Rg>zetab, suggesting PSS and network deformations in the latter case.
      Increasing ionic strength resulted in an increase in the PSS activation energy,
      because of the decrease of their radii of gyration, which makes them less
      deformable. Finally, the activation energies of all the PSSs are a decreasing
      function of field strength and at high field strength tend to reach a constant
      value close to that for a small molecule.

PMID- 11296924
TI  - Sieving matrices in capillary electrophoresis: inflection slope and double
      reciprocal plot.
AB  - We propose the use of a double reciprocal plot of the inflection slope and the
      concentration of a sieving polymer to compare sieving properties of polymers
      regardless of their concentration and to permit selection of appropriate sieving
      materials. Using this plot, the lines extrapolating the experimental values
      intersect the ordinate at the value corresponding to the inflection slope at the
      infinite concentration of the sieving polymer and the abscissa at the value
      characteristic for the given polymer. The latter corresponds to the polymer
      concentration at which the inflection slope equals half the inflection slope at
      an infinite polymer concentration. It is inversely proportional to intrinsic
      viscosity and this makes intrinsic viscosity an important physicochemical
      constant suitable for selection of new potent sieving polymers.

PMID- 11296925
TI  - Performances of new sugar-bearing poly(acrylamide) copolymers as DNA sieving
      matrices and capillary coatings for electrophoresis.
AB  - We have synthesized two new sugar monomers, allylamine of gluconic and
      lactobionic acid, by opening the corresponding lactone ring with allylamine.
      These monomers were copolymerized with acrylamide leading to formation of
      copolymers with a relative molecular mass of 288000 and 180000 Da, respectively.
      Double-stranded DNA fragments were separated in entangled solutions of these
      linear polymers in capillary electrophoresis. Resolution, peak spacing and peak
      width were the parameters taken into account to evaluate the quality of the
      separation achieved with the new polymers. This work indicates that the
      copolymers of acrylamide and allyl gluconic acid have a high sieving capacity and
      provide a performance similar to that of hydroxyethylcellulose (HEC) of
      comparable viscosity. Unlike HEC, this copolymer selfcoats onto the capillary
      wall, allowing DNA fragments to be efficiently separated in an uncoated
      capillary.

PMID- 11296926
TI  - Galactomannans as a sieving matrix in capillary electrophoresis.
AB  - Purification of galactomannans including guaran, tara gum, and locust bean gum is
      described as well as their use as a sieving matrix in DNA sequencing by capillary
      electrophoresis (CE). Three methods of galactomannan purification were developed
      and tested using guaran. The first method is based on hydrolysis of proteins
      using alkali treatment and precipitation of guaran with acetone. The second
      method uses ion-exchange resins QAE Sephadex A-25 and SP Sephadex C-25 together
      with acetone precipitation. The third method is similar to the second one, except
      that it uses ion-exchange resins based on polystyrene, Source 30Q and Source 30S.
      Capillary zone electrophoresis of acetonitrile extracts from guaran revealed 4-5
      characteristic major peaks and several minor peaks. Guar gum from different
      suppliers differed in the content of proteins. In purified guaran, protein peaks
      were detectable only using a 300-fold concentrate of extract. The content of
      proteins in the guaran purified using the third method was 0.001% m/m as
      determined by CE. The weight average molecular mass of purified guaran can be as
      large as 2.2 x 10(6). The purified galactomannans were used as a sieving matrix
      in DNA sequencing by CE. M13 DNA was sequenced to read lengths of about 600 bases
      in less than 90 min. Separation efficiencies exceeded 1 million theoretical
      plates for DNA fragments shorter than about 600 bases.

PMID- 11296927
TI  - New block-copolymer thermoassociating matrices for DNA sequencing: effect of
      molecular structure on rheology and resolution.
AB  - A new family of matrices for DNA sequencing by capillary electrophoresis is
      presented. These matrices combine easy injection with high sieving performances,
      due to thermal switching between a low and a high viscosity state through a
      modest increase in temperature (approximately 20 degrees C). They are constructed
      from a hydrophilic polymer backbone with grafted lower critical solution
      temperature (LCST) side chains. The comb-like LCST copolymers are characterized
      in terms of size of the polymer backbone, the size of LCST side chains and the
      grafting densities. The dependance of rheological behavior and electrophoretic
      performance of these copolymers is correlated with their microstructure. Without
      complete optimization, a resolution of order 0.5, corresponding to a very
      reasonable limit for read length with current base calling softwares, could be
      achieved for segments around 800 bases differing by 1 base in less than one hour
      in a commercial ABI 310 apparatus.

PMID- 11296928
TI  - DNA sequencing by capillary electrophoresis using copolymers of acrylamide and
      N,N-dimethylacrylamide.
AB  - Copolymers of acrylamide (AM) and N,N-dimethylacrylamide (DMA) with AM to DMA
      molar ratios of 3:1, 2:1 and 1:1 and molecular weights of about 2.2 MDa were
      synthesized. The polymers were tested as separation media in DNA sequencing
      analysis by capillary electrophoresis (CE). The dynamic coating ability of
      polydimethylacrylamide (PDMA) and the hydrophilicity of polyacrylamide (PAM) have
      been successfully combined in these random copolymers. A separation efficiency of
      over 10 million theoretical plates per meter has been reached by using the bare
      capillaries without the additional polymer coating step. Under optimized
      separation conditions for longer read length DNA sequencing, the separation
      ability of the copolymers decreased with decreasing AM to DMA molar ratio from
      3:1, 2:1 and 1:1. In comparison with PAM, the copolymer with a 3:1 AM:DMA ratio
      showed a higher separation efficiency. By using a 2.5% w/v copolymer with 3:1
      AM:DMA ratio, one base resolution of 0.55 up to 699 bases and 0.30 up to 963
      bases have been achieved in about 80 min at ambient temperatures.

PMID- 11296930
TI  - Optimization of DNA electrophoretic behavior in poly(vinyl pyrrolidone) sieving
      matrix for DNA sequencing.
AB  - Poly(vinyl pyrrolidone) solution was used as a separation matrix in capillary
      electrophoresis for DNA sequencing. Four-label four-color detection was performed
      for base calling. Dye-labeled DNA showed large mobility shifts at normal
      conditions for DNA separation. Temporal correction of mobility shifts was
      achieved by normalizing with respect to pure peaks that are without spectral
      interference or temporal overlap at each color channel. To achieve even better
      performance, a DNA separation condition that does not require corrections for
      mobility shifts was found. Dichlororhodamine-labeled DNA fragments showed ideal
      electrophoretic behaviors according to DNA size in the presence of 10 M urea. The
      base-calling accuracy of dichlororhodamine-labeled M13mp18 and PGEM/U DNA were
      99.3% for 333 bases and 99% for 315 bases, respectively. Base calling of unknown
      DNA samples obtained in the presence of 10 M urea showed 99.1% accuracy.

PMID- 11296929
TI  - Impact of polymer hydrophobicity on the properties and performance of DNA
      sequencing matrices for capillary electrophoresis.
AB  - To elucidate the impact of matrix chemical and physical properties on DNA
      sequencing separations by capillary electrophoresis (CE), we have synthesized,
      characterized and tested a controlled set of different polymer formulations for
      this application. Homopolymers of acrylamide and N,N-dimethylacrylamide (DMA) and
      copolymers of DMA and N,N-diethylacrylamide (DEA) were synthesized by free
      radical polymerization and purified. Polymer molar mass distributions were
      characterized by tandem gel permeation chromatography - laser light scattering.
      Polymers with different chemical compositions and similar molar mass
      distributions were selected and employed at the same concentration so that the
      variables of comparison between them were hydrophobicity and average coil size in
      aqueous solution. We find that the low-shear viscosities of 7% w/v polymer
      solutions decrease by orders of magnitude with increasing polymer hydrophobicity,
      while hydrophilic polymers exhibit more pronounced reductions in viscosity with
      increased shear. The performance of the different matrices for DNA sequencing was
      compared with the same sample under identical CE conditions. The longest read
      length was produced with linear polyacrylamide (LPA) while linear poly-N,N
      dimethylacrylamide (PDMA) gave approximately 100 fewer readable bases. Read
      lengths with DMA/DEA copolymers were lower, and decreased with increasing DEA
      content. This study highlights the importance of polymer hydrophilicity for high
      performance DNA sequencing matrices, through the formation of robust, highly
      entangled polymer networks and the minimization of hydrophobic interactions
      between polymers and fluorescently-labeled DNA molecules. However, the results
      also show that more hydrophobic matrices offer much lower viscosities, enabling
      easier microchannel loading at low applied pressures.

PMID- 11296931
TI  - Temperature and pH studies of short tandem repeat systems using capillary
      electrophoresis at elevated pH.
AB  - The DNA secondary structure can affect the migration time and precision of DNA
      separations in the physical gels used in capillary electrophoresis (CE). To
      counteract these effects, DNA typing is performed using elevated temperatures (60
      degrees C) and high concentrations (7 M) of urea. These conditions affect the
      precision and lifetime of the analysis. To better understand the effects of these
      conditions on the reproducibility of DNA migration, we examined the effects of
      temperature and pH on short tandem repeat (STR) analysis using the PE/ABI 310
      Genetic Analyzer. Separations were performed using the Profiler + multiplex
      system, a set of coamplified STRs with a 4-base repeat motif, labeled at the 5'
      end using fluorescent dyes. The analytical separations were obtained using a
      commercial buffer at pH 8 and an experimental buffer consisting of 3%
      hydroxyethylcellulose at pH settings ranging from 8-12. Multichannel laser
      induced fluorescence detection was used. Temperatures were examined from 30-70
      degrees C. The results demonstrate the fact that highly efficient separations can
      be carried out at alkaline pH. In addition, improvements in temperature stability
      were seen when compared to results at lower pH. However, high concentrations of
      urea were found to be necessary to achieve optimal resolution.

PMID- 11296932
TI  - A new strategy for optimizing sensitivity, speed, and resolution in capillary
      electrophoretic separation of DNA.
AB  - DNA separations were performed in poly(ethylene oxide) (PEO) solutions prepared
      in 100 mM Tris-boric acid (TB) buffers using a capillary filled with TB buffers
      with concentrations up to 2.5 M, pH 10.0. The electroosmotic flow (EOF) increased
      with increasing the concentration of TB buffers till 1.5 M as a result of
      decreasing PEO adsorption on the capillary wall. At high TB concentrations (> 1.5
      M), the peaks corresponding to small DNA fragments (11 and 8 base pairs) became
      sharper and were detected. Relative standard deviations of the EOF coefficient
      and the migration times of the DNA fragments were all less than 1% using a
      capillary filled with TB buffers at concentrations higher than 1.5 M. When
      separations were performed at different pH values of PEO solutions and TB
      buffers, better results in terms of sensitivity, speed, and resolution were
      generally achieved. The fluorescence intensity of the 2176 bp fragment obtained
      at pH values of TB buffers/PEO solutions 10.0/8.2 was 27-fold of that at pH
      values 8.2/8.2. The enhancement was related to effects of pH and borate on
      fluorescence intensity, DNA conformation, stacking, and interactions with the
      capillary wall. Using a capillary filled with 400 mM TB buffers, pH 10.0, the
      separation of DNA (pBR 322/HaeIII digest, pBR 328/Bg/I digest and pBR 328/HinfI
      digest) in 1.5% PEO solutions prepared in 100 mM TB buffers, pH 9.0, at 375 V/cm
      was accomplished in less than 18 min.

PMID- 11296933
TI  - Analysis of oligonucleotides and unincorporated nucleotides from in vitro
      transcription by capillary electrophoresis in Pluronic F127 gels.
AB  - Small functional RNAs required for structure studies are often prepared by in
      vitro transcription. Capillary electrophoresis in liquid crystalline gels of
      Pluronic F127 was used to analyze unfractionated in vitro transcription reactions
      and anion-exchange high-performance liquid chromatography (HPLC) fractions from
      transcription reactions. Guanosine monophosphate (GMP), the four nucleoside
      triphosphates (NTPs), abortive transcripts, and transcripts with lengths near the
      desired product length were simultaneously resolved and quantified in a single
      run. Oligonucleotides up to at least 35 nucleotides were resolved to baseline
      within 10 min using a moderate field (185 V/cm) and short effective capillary
      length (7.6 cm) for electrophoresis in 20% Pluronic F127 at pH 8.3 in Tris-borate
      EDTA (TBE) buffer (30 degrees C). Nucleotide migration times were 4-5 min, in the
      order UTP+CTP (unresolved) <ATP<GTP<GMP. A single capillary filling was reused
      for 40-50 runs with little decrease in performance, and for up to 100 runs with
      performance acceptable for many applications. Higher electric fields appeared to
      affect the gel structure and necessitated more frequent capillary refilling.
      Capillary gel electrophoresis (CGE) of HPLC fractions in Pluronic gels
      facilitates rapid recovery of RNA products and the large remaining amounts of
      valuable, isotopically labeled NTPs. In addition, comparison of electrophoretic
      patterns under denaturing and nondenaturing conditions yields insights into
      potential conformational heterogeneity of the folded nucleic acid states. CGE in
      Pluronic gels provides a rapid, highly discriminating means for analyzing in
      vitro transcription reactions.

PMID- 11296934
TI  - Rapid single nucleotide polymorphism analysis by primer extension and capillary
      electrophoresis using polyvinyl pyrrolidone matrix.
AB  - Rapid molecular diagnosis of 21-hydroxylase deficiency by detecting the most
      common mutation in the 21-hydroxylase gene is presented using primer extension
      and capillary electrophoresis with a polyvinyl pyrrolidone matrix. DNA samples
      were subjected to polymerase chain reaction (PCR) in order to amplify a 422 bp
      fragment of the CYP21 gene containing the single nucleotide polymorphism (SNP)
      site. This product served as a template in the primer extension reaction using a
      fluorescently labeled primer in close proximity to the SNP. ddGTP was used to
      block the extension if the mutation was present and the other three dNTPs to
      enable elongation of the primer. Fast analysis of the resulting fragments was
      performed by capillary electrophoresis using 10% polyvinylpyrrolidone as sieving
      and wall coating matrix. The Cy5-labeled primer and the two possible primer
      extension products (mutant and wild type) were completely separated in 90 s.

PMID- 11296935
TI  - Fast separation of DNA sequencing fragments in highly alkaline solutions of
      linear polyacrylamide using electrophoresis in bare silica capillaries.
AB  - An optimized procedure for the fast separation of DNA sequencing fragments in
      short bare fused-silica capillaries filled with highly alkaline solutions of
      replaceable linear polyacrylamide is presented. High denaturing abilities of the
      separation media at pH values over 12 are the main reason for their applications
      in analyses of ssDNA fragments. Moreover, the alkaline solutions of
      polyacrylamide provide other advantageous properties: three times higher
      electrophoretic mobility of ssDNA fragments in comparison to those in urea,
      negligibly low electroosmotic flow in uncoated capillaries, and an adequate
      stability to a fast alkaline hydrolysis. The separation power of this procedure
      is enhanced strongly by using monocarboxy poly(ethylene glycol), a terminator for
      transient isotachophoresis, which eliminates the electromigration dispersion. A
      high separation efficiency of our system enables to reduce analysis time to
      several minutes by decreasing the effective lengths of capillaries to 7 cm. A
      special sample introduction by diffusion is successfully applied. The
      experimental results demonstrate a potential of the alkaline electrolytes for an
      implementation in diagnostic sequencing practice.

PMID- 11296936
TI  - Association of leisure-time noise exposure and hearing loss.
AB  - The purpose of this study was to investigate the association of noisy leisure
      activities with hearing loss. Participants (n=3571) were examined in a population
      based study of age-related hearing loss conducted in Beaver Dam, Wisconsin.
      Hearing thresholds were determined by audiometry. Hearing loss was defined as the
      pure-tone average of the frequencies 500, 1,000, 2,000, and 4,000 Hz greater than
      25 dB HL in either ear. Information regarding exposure to leisure-time noise was
      obtained by interview. After adjusting for potential confounders, individuals who
      engaged in leisure activities with average sound levels greater than 90 dBA were
      significantly more likely to have a hearing loss than participants who did not
      engage in noisy leisure activities (OR=1.11, 95 per cent CI=1.01-1.22).
      Individuals who engaged in woodworking were 30 per cent more likely to have a
      hearing loss than those who had never done woodworking. There was a 6 per cent
      increased risk of hearing loss for each 5-year period of participation. Health
      care professionals should consider counseling their patients who engage in noisy
      leisure activities about the risk of noise-induced hearing loss.

PMID- 11296937
TI  - Effects of single-channel phonemic compression schemes on the understanding of
      speech by hearing-impaired listeners.
AB  - The effect of digital processing on speech intelligibility was studied in hearing
      impaired listeners with moderate to severe high-frequency losses. The amount of
      smoothed phonemic compression in a high-frequency channel was varied using wide
      band control. Two alternative systems were tested to compensate for upward spread
      of masking (USOM) and to reduce modulations in the high-frequency channel
      effectively. Consonant-vowel-consonant tests were conducted in a group of 14
      subjects using eight different speech-processing settings. Speech intelligibility
      improved significantly with compression, mainly due to positive effects on the
      initial-consonant score. Surprisingly, listeners with a smaller residual dynamic
      range tended to profit less from compression. Compensation for USOM gave an
      additional improvement of vowel intelligibility. In background noise,
      consistently negative effects of speech processing were found. The combined use
      of phonemic compression and USOM compensation is promising in conditions without
      background noise.

PMID- 11296938
TI  - Hearing performance in noise of cochlear implant patients versus severely
      profoundly hearing-impaired patients with hearing aids.
AB  - It is possible for most post-lingually deaf patients to attain significant open
      speech recognition following cochlear implantation. In contrast, many severely
      profoundly sensorineural hearing-impaired patients receive no benefit from their
      hearing aids, especially in situations with background noise. The aim of the
      study was to evaluate the speech recognition ability in quiet and in noise of
      post-lingually deaf adults implanted with Combi 40/40+ cochlear implants versus
      severely-profoundly sensorineural hearing-impaired patients fitted with hearing
      aids. For this purpose, we tested two groups of patients: one that had received
      cochlear implants (n=22) and a group of subjects with severe-profound
      sensorineural hearing impairment, fitted with hearing aids (n = 15). All of the
      patients were tested using the Hochmaier, Schultz, and Moser Discrimination Test
      in quiet and noise. The results of the study demonstrate that most of our
      cochlear implant patients received a substantial benefit from their implant,
      achieving scores of 70 to 100 per cent (mean, 90 per cent) for the numbers test
      and 10 to 72 per cent (mean, 43 per cent) for the monosyllable test 1 year after
      implantation. Even in situations with background noise, scores of 1 to 99 per
      cent (mean, 45.65 per cent) for a signal to noise ratio (SNR) of +15 dB 1 year
      following the implantation improved to 7 to 95 per cent (mean, 50.7 per cent) at
      2 years and 8 to 99 per cent (mean, 60 per cent) at 3 years after implantation.
      These results are significantly (p<0.04) superior to the hearing aid patients'
      scores of 1 to 64.2 per cent (mean, 26.7 per cent) for a SNR of 15 dB. The
      results of the present study may have clinical implications in regard to
      selection of candidates for cochlear implantation.

PMID- 11296939
TI  - Comparison of speech recognition with different speech coding strategies (SPEAK,
      CIS, and ACE) and their relationship to telemetric measures of compound action
      potentials in the nucleus CI 24M cochlear implant system.
AB  - Speech understanding and subjective preference for three different speech coding
      strategies (spectral peak coding [SPEAK], continuous interleaved sampling [CIS],
      and advanced combination encoders [ACE]) were investigated in 11 post-lingually
      deaf adult subjects, using the Nucleus CI 24M cochlear implant system. Subjects
      were randomly assigned to two groups in a balanced crossover study design. The
      first group was initially fitted with SPEAK and the second group with CIS. The
      remaining strategies were tested sequentially over 8 to 10 weeks with systematic
      variations of number of channels and rate of stimulation. Following a further
      interval of 3 months, during which subjects were allowed to listen with their
      preferred strategy, they were tested again with all three strategies. Compound
      action potentials (CAPs) were recorded using neural response telemetry.
      Input/output functions in relation to increasing stimulus levels and inter
      stimulus intervals between masker and probe were established to assess the
      physiological status of the cochlear nerve. Objective results and subjective
      rating showed significant differences in favour of the ACE strategy. Ten of the
      11 subjects preferred the ACE strategy at the end of the study. The estimate of
      the refractory period based on the inter-stimulus interval correlated
      significantly with the overall performance with all three strategies, but CAP
      measures could not be related to individual preference of strategy or differences
      in performance between strategies. Based on these results, the ACE strategy can
      be recommended as an initial choice specifically for the Nucleus CI 24M cochlear
      implant system. Nevertheless, access to the other strategies may help to increase
      performance in individual patients.

PMID- 11296940
TI  - Clinical study of hearing instruments: a cross-sectional longitudinal audit based
      on consumer experiences.
AB  - The objective of the present audit was to document improvements/changes in
      hearing instrument (HI) benefit in terms of use and satisfaction throughout the
      1990s and compare the benefit in consumers fitted with analogue (A), programmable
      (P), and digital signal processing (DSP) HIs. The audit data are based on a
      questionnaire mailed to subjects fitted with HIs 3 to 4 months after the fitting,
      including questions concerning satisfaction with the HI, use of the HI, ability
      to manage the HI, and satisfaction with the overall services in the department.
      Information was obtained from 32,694 subjects (i.e., 71.2 per cent of those
      fitted with HIs throughout the last decade), with a median age at fitting of 78
      years (range, 18-102), with a preponderance of females. No significant
      differences in age, gender distribution, and hearing instrument distribution were
      found between the respondents and non-respondents. The audit shows that there are
      no significant differences in any of the benefit parameters throughout the
      decade, irrespective of the introduction of P-HIs in 1995 and of the DSP-HIs in
      1998. Thus, from the consumers' perspective, no changes have appeared in the last
      decade. A comparative analysis of the A-HIs, P-HIs, and DSP-HIs shows that among
      those provided with P-HIs and DSP-HIs, only 69.6 per cent (CI 68.1-71.0) and 65.5
      per cent (CI 60.2-78.8), respectively, were very satisfied/satisfied with the HI,
      which is significantly less than the 73.5 per cent (CI 72.4-74.5) in those fitted
      with A-HIs. The daily/weekly use of all three types of HIs was similar. However,
      the group fitted with DSP-HIs was significantly less satisfied with the general
      services compared with those fitted with A-HIs and P-HIs, respectively. Based on
      these audit data, it is concluded that, according to the consumers, the outcome
      from HIs has not changed over the last decade, and a comparison between the
      traditional A-HIs with both P-HIs and DSP-HIs is in favour of the traditional A
      HIs.

PMID- 11296941
TI  - Endogenous retroviruses in pathogenesis of autoimmunity.

PMID- 11296942
TI  - Primary angiitis of the central nervous system: the penumbra of vasculitis.

PMID- 11296943
TI  - Should the initial drug be used to treat osteoarthritis pain be a nonsteroidal
      antiinflammatory drug?

PMID- 11296944
TI  - Rheumatoid arthritis and hepatitis B virus: evaluating the pathogenic link.

PMID- 11296945
TI  - Identification of alpha6beta1 integrin positive cells in synovial lining layer as
      type B synoviocytes.
AB  - OBJECTIVE: In rheumatoid arthritis (RA) the synovial lining is responsible for
      cartilage destruction. Laminin is one of the major matrix molecules surrounding
      the lining cells. We investigated the laminin adhesion mechanism of synovial
      lining cells by analyzing the presence of its receptor, alpha6beta1 integrin, on
      type A and type B synoviocytes. METHODS: The alpha6 integrin subunit and a
      macrophage marker were simultaneously localized by immunohistochemistry in 29 RA
      derived, 6 osteoarthritis derived, and 2 healthy synovial samples by light and
      electron microscopy. We also used enzyme treatments to release cells from
      synovial tissue samples and localized the same antigens on adherent cells.
      RESULTS: The alpha6beta1 integrin positive cells were localized in basal areas of
      the lining layer and many of them were negative for the macrophage markers. By
      immunolabeling electron microscopy the alpha6 integrin positive cells were
      confirmed to represent the fibroblast-like type B cells. Further, in freshly
      isolated synoviocyte cultures the type B cells were positive for alpha6 integrin,
      whereas all other cell types were negative for this laminin receptor. CONCLUSION:
      Integrin alpha6beta1 is known to be a laminin receptor of endothelial cells,
      adipocytes, and macrophages, not usually expressed on fibroblasts. However, in
      synovial lining layer it is expressed on fibroblastic type B cells, but the
      macrophage population is negative. The unique characteristics of synovial lining
      cells distinguish them from other connective tissue cells and must be taken into
      account in all considerations of the pathogenic mechanisms of rheumatoid disease.

PMID- 11296946
TI  - Correlations between matrix metalloproteinase-9 and adenosine deaminase isozymes
      in synovial fluid from patients with rheumatoid arthritis.
AB  - OBJECTIVE: To clarify the significance of increased adenosine deaminase (ADA)
      isozyme activities in synovial fluid (SF) from patients with rheumatoid arthritis
      (RA). METHODS: ADA isozyme activities were measured using colorimetric assays.
      Concentrations of matrix metalloproteinase-9 (MMP-9) were measured by ELISA.
      RESULTS: Levels of ADA isozyme activities in RA SF were significantly higher than
      those from patients with osteoarthritis and patients with traumatic injuries.
      Significant positive correlations between MMP-9 concentration and ADA activities
      were observed in RA SF (MMP-9 vs total ADA: r = 0.880; vs ADA1: r = 0.829; vs
      ADA2: r = 0.823; p < 0.001). CONCLUSION: Elevated levels of ADA activities were
      found in SF from patients with RA. There were significant positive correlations
      between MMP-9 and ADA isozymes. These results may reflect the inflammatory
      condition of patients with RA.

PMID- 11296947
TI  - Serum levels of interleukin 6 and stress related substances indicate mental
      stress condition in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the influence of mental stress on the neuroendocrine
      immune system in patients with rheumatoid arthritis (RA). METHODS: Twenty-two
      patients with RA and 8 patients with osteoarthritis (OA) who underwent total knee
      or hip arthroplasties under general anesthesia were enrolled in the study. The
      blood levels of interleukin 6 (IL-6) and other substances related to stress were
      measured just before administering anesthesia on the day of the operation when
      the patients lay on the operating table and roughly 30 min later when the
      patients were under general anesthesia without mental stress. These values were
      compared with those at the same time on the day before the operation, which were
      considered the control levels. RESULTS: In patients with RA, the levels of IL-6,
      cortisol, and epinephrine in the peripheral blood were significantly increased
      under mental stress, before anesthesia (p < 0.01). However, under general
      anesthesia, the IL-6, cortisol, and epinephrine were significantly decreased,
      compared with the levels before anesthesia (p < 0.01). Such changes were not
      apparent in patients with OA. The levels of other substances in the peripheral
      blood known to be related to stress, such as corticotropin-releasing factor,
      dopamine, and norepinephrine, showed no changes in patients with RA or OA.
      CONCLUSION: In patients with RA, excessive mental stress should be eliminated to
      modify the interaction between the stress-immune system and stress-endocrine
      system as a method to better control disease activity.

PMID- 11296948
TI  - Enhanced in vitro induced production of interleukin 10 by peripheral blood
      mononuclear cells in rheumatoid arthritis is associated with clinical response to
      methotrexate treatment.
AB  - OBJECTIVE: To investigate the effect of in vivo treatment with methotrexate (MTX)
      on the regulation of ex vivo interleukin 10 (IL-10) production by peripheral
      blood mononuclear cells (PBMC) derived from patients with rheumatoid arthritis
      (RA). METHODS: Spontaneous as well as lipopolysaccharide (LPS) and
      phytohemagglutinin (PHA) induced IL-10 release was assessed by a specific
      immunoassay in culture supernatants of PBMC derived from 32 patients with active
      RA before and 6, 12, and 24 weeks after MTX treatment. IL- 10 production was
      correlated to the clinical response. As a control, IL-10 release from PBMC of 7
      healthy blood donors was determined. RESULTS: PBMC of patients with RA showing >
      50% improvement of the Paulus index after 3 and 6 months of MTX treatment
      (responders; n = 18) exhibited significantly enhanced IL-10 production after in
      vitro stimulation with LPS, whereas constitutively released IL-10 was below the
      detection limit of the immunoassay in all patients and controls. In contrast, IL
      10 release from LPS stimulated PBMC of RA patients who showed < 20% improvement
      by Paulus index (nonresponders; n = 14) or who even deteriorated compared to
      baseline disease activity was markedly downregulated during MTX treatment in
      vivo. PHA-induced IL-10 release from PBMC in vitro was not significantly affected
      by MTX in vivo whether RA patients responded or not to MTX. CONCLUSION: Enhanced
      ex vivo LPS induced IL-10 production by PBMC of patients with RA is associated
      with a favorable therapeutic response to MTX treatment, whereas reduced
      production coincides more closely with disease deterioration or insufficient
      response. This may reflect both disease outcome upon treatment and/or the mode of
      the antiinflammatory action of MTX in RA. Because the LPS--but not the PHA-
      induced ex vivo IL-10 production by PBMC was stimulated by MTX in vivo, monocytes
      seem to be the prominent target cells for this drug mediated antiinflammatory
      cytokine regulation.

PMID- 11296949
TI  - Methotrexate stimulates lung fibroblasts and epithelial cells to release
      eosinophil chemotactic activity.
AB  - OBJECTIVE: To determine if methotrexate (MTX) induces human lung fibroblast (HFL
      1) and epithelial (BEAS 2B) cell lines to release eosinophil chemotactic activity
      (ECA). METHODS: HFL-1 and BEAS 2B cell supernatant fluids were evaluated for ECA
      by a blind well chamber technique. RESULTS: HFL-1 and BEAS-2B cells released ECA
      in a dose and time dependent manner in response to MTX. Partial characterization
      revealed that ECA was partly heat labile, trypsin sensitive, and ethylacetate
      extractable. Thus the culture supernatant fluids were evaluated for known
      eosinophil chemotactic factors. Although several were released constitutively,
      granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly
      increased in response to MTX from both cell types. Consistent with these
      observations, ECA from both cell types was inhibited by GM-CSF antibodies.
      CONCLUSION: These data suggest that lung fibroblasts and epithelial cells may
      modulate eosinophil recruitment into the lung by releasing ECA in response to
      MTX.

PMID- 11296950
TI  - Relationship between parity and clinical and biological features in patients with
      systemic sclerosis.
AB  - OBJECTIVE: To assess the influence of parity on the clinical and biological
      features of systemic sclerosis (SSc). METHODS: We recorded the following clinical
      and biological data of 100 consecutive women with SSc: age, disease duration
      before diagnosis, cutaneous extension of sclerosis according to LeRoy's
      classification, pulmonary involvement, and antinuclear antibodies. We compared
      these features to the number and sex of children who were born before SSc onset.
      Date of birth of the first children was systematically recorded. RESULTS:
      Patients with limited SSc had more children before SSc onset than patients with
      diffuse SSc (2.4 +/- 1.8 vs 1.7 +/- 1.5; p < 0.05). The interval between first
      birth and SSc onset was shorter for patients with limited SSc than for patients
      with diffuse SSc (11.0 +/- 9.9 vs 23.5 +/- 14.5 yrs; p < 0.01). Patients with
      pulmonary fibrosis had more children than patients without pulmonary fibrosis
      (2.5 +/- 1.9 vs 2.0 +/- 1.6; p < 0.05). Age at first birth was significantly
      higher when the child was a girl than a boy (26.8 +/- 7.5 vs 22.9 +/- 5.3 yrs; p
      < 0.05). The interval between the first birth and SSc onset was shorter when the
      child was a girl than a boy (16.2 +/- 9.6 vs 25.4 +/- 13.4 yrs; p < 0.05).
      CONCLUSION: Pregnancy related microchimerism could be preferentially associated
      with limited SSc and pulmonary fibrosis. Microchimerism may be facilitated in
      cases in which the fetus is female.

PMID- 11296951
TI  - Persistent increase in plasma thrombomodulin in patients with a history of lupus
      nephritis: endothelial cell activation markers.
AB  - OBJECTIVE: To investigate the presence of continuing endothelial cell activation
      in patients with systemic lupus erythematosus (SLE) and its relationship with
      lupus nephritis. METHODS: We measured plasma concentrations of soluble
      thrombomodulin (sTM), vascular cellular adhesion molecule-1 (sVCAM-1), von
      Willebrand factor (vWf), sP-selectin, and ED1-fibronectin in 75 SLE patients with
      a median SLE disease activity index (SLEDAI) of 4. Forty patients with a history
      of lupus nephritis, confirmed by renal biopsy in 33, were compared with 35
      patients without lupus nephritis and 25 controls. For subgroup analysis in
      patients with clinically stable remission we excluded patients with a SLEDAI > 6
      or with evidence of renal disease activity. RESULTS: In the total SLE patient
      group sTM, sVCAM-1, vWf, and sP-selectin were significantly elevated compared
      with controls. In patients with a history of lupus nephritis plasma levels of sTM
      and vWf were significantly increased compared with SLE patients without
      nephritis. After adjustment for significantly associated variables, especially
      creatinine clearance and age, in a multivariate linear regression analysis, sTM
      remained significantly elevated in patients with a history of lupus nephritis
      (difference 28.9 ng/ml, 95% CI 11.5-46.4). In the subgroup analysis of 57
      patients, the results remained unchanged. CONCLUSION: The increase of sVCAM-1, sP
      selectin, sTM, and vWf reflects a state of persistent endothelial cell
      activation. Multivariate regression analysis shows that the elevated sTM levels
      are strongly associated with a history of lupus nephritis, independent of
      creatinine clearance or disease activity, suggesting endothelial cell activation
      specifically localized in the kidneys.

PMID- 11296952
TI  - Isotypes of anti-beta2-glycoprotein I antibodies: association with thrombosis in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the association between isotypes of anti-beta2
      glycoprotein I antibodies (anti-beta2-GPI) and thrombosis and to identify
      antiphospholipid antibodies (aPL) that are most associated with thrombosis in
      patients with systemic lupus erythematosus (SLE). METHODS: IgG anticardiolipin
      antibody (aCL) and isotypes of anti-beta2-GPI were measured by ELISA, and
      clinical evidence of thrombosis was analyzed in 270 patients with SLE. RESULTS:
      IgG, IgM, and IgA anti-beta2-GPI were positive in 38.1, 13.7, and 34.8% of
      patients, respectively. Patients with a history of thrombosis were significantly
      more likely to have lupus anticoagulant (LAC), IgG aCL, and the 3 anti-beta2-GPI
      isotypes. Arterial thrombosis was associated with the presence of IgG aCL and the
      3 anti-beta2-GPI isotypes, whereas venous thrombosis was associated with LAC, IgG
      aCL, and IgA anti-beta2-GPI. In stepwise multivariate logistic regression
      analysis, the variable that was associated with thrombosis was IgA anti-beta2
      GPI. The occurrence of arterial thrombosis was associated with IgG aCL and that
      of venous thrombosis was related to IgA anti-beta2-GPI in stepwise multivariate
      analysis. The IgG, IgM, and IgA anti-beta2-GPI titers were closely correlated
      with IgG aCL titers. The IgA anti-beta2-GPI titers were also significantly
      correlated with those of IgG and IgM anti-beta2-GPI. CONCLUSION: The results
      suggest that anti-beta2-GPI isotypes are related to the occurrence of thrombosis,
      and measurements of IgA anti-beta2-GPI may be useful for predicting thrombotic
      episodes in patients with SLE.

PMID- 11296953
TI  - The relationship between health related quality of life and disease activity and
      damage in systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the relationship between self-reported quality of life and
      disease activity, damage, impairment, disability, and handicap in systemic lupus
      erythematosus (SLE). METHODS: In this cross sectional study disease activity was
      measured with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
      and the Systemic Lupus Activity Measure (SLAM), and damage by the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology (SLICC/ACR)
      damage index (SDI). Quality of life was assessed by the Medical Outcome Survey
      Short Form 36 (SF-36) and the EuroQol (EQ-5D). Multiple linear regression was
      used to identify significant associations of patients' health status, and
      logistic regression was used to evaluate the relationship of each of the 5
      dimensions of the EQ-5D in terms of impairment, disability, and handicap.
      RESULTS: Damage was associated with the Physical Function (PF) and Social
      Function subscales of the SF-36. Disease activity was associated with the General
      Health (GH) subscale. Ability to carry out usual activities was strongly related
      to PF and GH as well as to global rating of the thermometer rating scale of the
      EQ-5D. Role Physical (RP) and Bodily Pain (BP) of the SF-36 were also associated
      with the EQ-5D rating scale. In addition, patients' ratings of anxiety and
      depression were strongly related to the Mental Health (MH) summary scale of the
      SF-36. CONCLUSION: Perceived health status of patients with lupus was associated
      with disease activity, damage, role physical, bodily pain, capacity for usual
      activity, and mobility. EQ-5D is a valid instrument for the measure of health
      related quality of life in SLE.

PMID- 11296954
TI  - Quantitative analyses of messenger RNA of human endogenous retrovirus in patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: Human endogenous retrovirus (HERV) has emerged as a possible causative
      agent of systemic lupus erythematosus (SLE). To investigate the role of HERV in
      the etiology of SLE, we performed quantitative analyses of messenger RNA (mRNA)
      of the HERV clone 4-1 in patients with SLE. METHODS: Reverse transcriptase (RT)
      polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR; TaqMan
      methodology) were used in this experiment. RESULTS: The quantities of mRNA of the
      HERV clone 4-1 gag region in patients with SLE were significantly higher than in
      healthy controls, and the amounts of such mRNA in the patients were decreased by
      steroid treatment. CONCLUSION: These phenomena may be related to the production
      of viral components derived from HERV clone 4-1 and contribute to the
      pathogenesis of SLE; studies using a larger number of patients are required to
      confirm these points.

PMID- 11296955
TI  - Systemic lupus erythematosus in the Arctic region of Norway.
AB  - OBJECTIVE: The marked regional variation in the incidence, prevalence, and
      presentation of systemic lupus erythematosus (SLE) is possibly related to
      differing spectra of local environmental factors. The aim of this study was to
      describe such features in a homogenous Caucasian population exposed to an Arctic
      climate. METHODS: The study area consisted of the 2 northernmost counties of
      Norway (middle population 222,403) where 4 hospitals (containing only one
      rheumatology service) provide specialized health care. Retrieval sources were (1)
      hospital inpatient discharge registries; (2) hospital outpatient registries; (3)
      mortality database of the National Office for Statistics. Databases were searched
      with codes for SLE, S ogren's syndrome, unclassified connective tissue disease,
      and discoid lupus for the period 1978-96. Only patients meeting 1982 American
      College of Rheumatology criteria for SLE were included in the analysis. Annual
      incidence rate (AIR), point prevalence (PP), and mortality rates were estimated
      per 100,000 at risk. RESULTS: Eighty-three incident cases of adult SLE (87%
      female, mean age 40.6 yrs at diagnosis) were encountered. Crude AIR of SLE in the
      whole study period was 2.6 (95% CI 1.9-2.9) for adults. Sex-specific AIR was 4.6
      for adult women and 0.6 for adult men. AIR in the first (2.4) and second 9-year
      period (2.7) was similar (p > 0.2). The crude overall PP for SLE at January 1,
      1996, was 44.9 and was highest in women aged 3149 (PP 102.5). Mortality in
      incident cases was 9.6% (after a mean followup of 99 mo) with overall 10-year
      survival estimated at 75%. CONCLUSION: In a Caucasian population exposed to the
      Arctic climate incidence of SLE is rather low and stable. Course and presentation
      of SLE in the Arctic is not different from similar populations in the Western
      world. Improved outcome now makes SLE a disease present in 1 per 1,000 Norwegian
      women aged > 30 years.

PMID- 11296956
TI  - Whole body and regional bone mineral density in ankylosing spondylitis.
AB  - OBJECTIVE: To study the regional distribution of bone mass and look for factors
      leading to bone loss in ankylosing spondylitis (AS). METHODS: Thirty-nine
      patients, all men, aged 20 to 55 years and presenting with AS were studied. Four
      hundred sixteen gendarmes, all men aged 20 to 55 years, formed an age matched
      control population used to define standard values for bone mineral density (BMD)
      in men. The patients with AS and the controls underwent measurement of whole body
      BMD and regional BMD by dual-energy x-ray absorptiometry. RESULTS: AS was
      associated with spinal bone loss, with lumbar spine BMD (LSBMD) 1.085 +/- 0.178
      g/cm2 in the AS group compared with 1.232 +/- 0.136 g/cm2 in the control group (p
      < 0.01). Whole body BMD and regional BMD of head, whole spine, pelvis, and legs
      were reduced, although this was not statistically significant. Using standard
      values for LSBMD from the controls, we found that 46% (18/39) of patients with AS
      had Z score < -1.5 SD. Biological markers of disease activity were higher in the
      subgroup of patients with low LSBMD than in the subgroup with normal LSBMD, with
      an erythrocyte sedimentation rate of 29.4 +/- 23.4 mm/h versus 12.1 +/- 10.8 mm/h
      (p < 0.05) and C-reactive protein at 24.8 +/- 18 mg/l versus 12.7 +/- 14.2 mg/l
      (p < 0.05). CONCLUSION: AS is associated with bone loss, mainly concerning the
      lumbar spine, in patients whose disease is biologically most active.

PMID- 11296957
TI  - Familial aggregation of ankylosing spondylitis in Southern China.
AB  - OBJECTIVE: To study the familial aggregation of ankylosing spondylitis (AS) in
      southern China and to compare the clinical and laboratory characteristics between
      the probands and their first-degree relatives with AS. METHODS: On the basis of
      questionnaires to 473 patients with AS, 402 responded and 36 self-reported having
      first-degree relatives with symptoms related to spondyloarthropathies. All
      together, 144 of 150 first-degree relatives of these 36 probands were examined
      for clinical and radiographic characteristics. HLA typing for HLA-B27 was
      performed by standard microlymphocytotoxicity method. RESULTS: The disease
      duration of the 36 probands was 5.03 +/- 3.76 years (0.5-14 yrs). Forty seven
      first-degree relatives of the 36 probands were diagnosed as having AS. The
      prevalence of AS among the first-degree relatives of these 36 aggregated families
      was 31.3%. The overall prevalence of AS among the first-degree relatives in these
      402 families was estimated to be 2.8%. The recurrence risk of the first-degree
      relatives within these aggregated families was 31.3%, suggesting an excess risk
      to them of 120.4, while it was 10.8 to the general families. The probands more
      often had peripheral arthritis and enthesopathies (p < 0.001 and p = 0.01,
      respectively) than the AS patients among the first-degree relatives. HLA-B27 was
      associated with development of AS in the probands and the patients among the
      first-degree relatives. CONCLUSION: Although familial aggregation of AS in
      southern China is uncommon in general, the recurrence risk of the first-degree
      relatives of AS probands within the aggregated families is extremely high,
      according to our study among hospital based patients. As the disease of the first
      degree relatives is often mild and atypical, familial background analysis should
      be encouraged to assist early diagnosis.

PMID- 11296958
TI  - Spondyloarthropathies in Japan: nationwide questionnaire survey performed by the
      Japan Ankylosing Spondylitis Society.
AB  - OBJECTIVE: The Japan Ankylosing Spondylitis Society conducted a nationwide
      questionnaire survey of spondyloarthropathies (SpA) in 1990 and 1997, (1) to
      estimate the prevalence and incidence, and (2) to validate the criteria of Amor
      and the European Spondylarthropathy Study Group (ESSG) in Japan. METHODS: Japan
      was divided into 9 districts, to each of which a survey supervisor was assigned.
      According to unified criteria, each supervisor selected all the clinics and
      hospitals with potential for SpA patients in the district. The study population
      consisted of all patients with SpA seen at these institutes during a 5 year
      period (1985-89) for the 1st survey and a 7 year period (1990-96) for the 2nd
      survey. RESULTS: The 1st survey recruited 426 and the 2nd survey 638 cases, 74 of
      which were registered in both studies. The total number of patients with SpA
      identified 1985-96 was 990 (760 men, 227 women). They consisted of patients with
      ankylosing spondylitis (68.3%), psoriatic arthritis (12.7%), reactive arthritis
      (4.0%), undifferentiated SpA (5.4%), inflammatory bowel disease (2.2%),
      pustulosis palmaris et plantaris (4.7%), and others (polyenthesitis, etc.)
      (0.8%). The maximum onset number per year was 49. With the assumption that at
      least one-tenth of the Japanese population with SpA was recruited, incidence and
      prevalence were estimated not to exceed 0.48/100,000 and 9.5/100,000 person
      years, respectively. The sensitivity was 84.0% for Amor criteria and 84.6 for
      ESSG criteria. CONCLUSION: The incidence and prevalence of SpA in Japanese were
      estimated to be less than 1/10 and 1/200, respectively, of those among
      Caucasians. The adaptability of the Amor and ESSG criteria was validated for the
      Japanese population.

PMID- 11296959
TI  - Primary ankylosing spondylitis: patterns of disease in a Brazilian population of
      147 patients.
AB  - OBJECTIVE: To analyze patterns of disease in a population of Brazilian patients
      with primary ankylosing spondylitis (AS). METHODS: Retrospective study (1988-98)
      analyzing 147 patients with a diagnosis of primary AS according to the modified
      New York criteria. Selected patients had complete clinical (initial symptom,
      axial and peripheral involvement, heel enthesitis, extraarticular manifestations)
      and radiological (sacroiliac, lumbar, thoracic, and cervical spine)
      investigations, and these data were compared with sex, race, age at onset, and
      HLA-B27. RESULTS: There was a predominance of men (84.4%), Caucasian race
      (75.5%), adult onset (> 16 years, 85%), and positive HLA-B27 (78.2%). Family
      history of AS was noted in 14.3% of the patients. Pure axial AS was observed in
      37 patients (25.2%). The predominant initial symptoms were inflammatory low back
      pain (61.9%) and peripheral arthritis (22.4%). Thoracic and cervical spine
      involvement was noted in 70.1% of the patients; radiological findings included
      syndesmophytes in 46.9% and "bamboo spine" in 20.4% of patients. The extraaxial
      joints most frequently involved were: ankles (39.5%), hips (36.1%), knees
      (29.3%), shoulders (19%), and sternoclaviculars (14.3%); heel enthesitis was
      present in 22.4%. Acute anterior uveitis was noted in 14.3% of patients. Male sex
      was associated with involvement of thoracic spine (p = 0.002), cervical spine (p
      = 0.002), and hips (p = 0.042), whereas female sex was associated with
      sternoclavicular (p = 0.024) involvement. Caucasian race presented higher
      frequency of positive family history (p = 0.023); there was no statistical
      significance of clinical and radiological variables compared with African
      Brazilians. Juvenile onset AS presented higher frequency of ankle (p = 0.012) and
      knee (p = 0.001) involvement, heel enthesitis (p = 0.001), and total hip
      replacement (p = 0.038), whereas adult onset was associated with thoracic (p =
      0.026) and cervical spine (p = 0.026) involvement and positive family history (p
      = 0.044). Positive HLA-B27 was associated with ankle involvement (p = 0.007) and
      heel enthesitis (p = 0.013). CONCLUSION: In this population women showed a milder
      axial involvement, Caucasian race presented axial and peripheral involvement
      similar to African-Brazilians, juvenile onset AS was associated with articular
      involvement of the lower limbs, and positive HLA-B27 was associated with ankle
      involvement.

PMID- 11296960
TI  - Prevention of corticosteroid induced osteoporosis in inpatients recently
      discharged from a tertiary teaching hospital.
AB  - OBJECTIVE: To determine the medical conditions for which oral corticosteroids are
      prescribed and to determine the frequency and type of osteoporosis prophylaxis
      offered to these patients. METHODS: Medical records of all inpatients for the
      period March to October 1999 who were documented in pharmacy records as either
      having received continuous oral steroids for at least 3 months or who had at
      least 4 courses of oral steroids per year were examined for the following data:
      age, sex, medical condition for which steroids were required, dose and duration
      of steroid therapy, whether they were offered bone mineral density (BMD) scans,
      and whether they were offered drug prophylaxis for steroid induced osteoporosis
      and the type of drug prophylaxis offered. Followup telephone calls were made to
      verify patients' use of prophylactic treatment and to validate the chronic use of
      oral corticosteroids. Use of BMD testing was also validated by comparing the list
      of patients in this study with the records of bone densitometer units in the
      area. RESULTS: A total of 189 medical records were examined: 38% were women (n =
      72) and 62% were men (n = 117), with an age range of 19-91 years; 73% were taking
      continuous steroid therapy, the remaining 27% had multiple courses of
      prednisolone through the year. Steroids were prescribed for respiratory (n = 82,
      43%), rheumatological (n = 74, 39%), hematological (n = 16, 8%), dermatological
      (n = 8, 4%), and gastrointestinal conditions (n = 7, 4%). Chronic obstructive
      airway disease was the most common respiratory condition for which steroids were
      prescribed (77, 94%), and polymyalgia rheumatica (36%) and inflammatory arthritis
      (41%) were the most common rheumatological conditions for which steroids were
      prescribed. In total, 47% (n = 89) were offered BMD scans while 53% (n = 100)
      were not. Of the 100 patients not offered BMD scans, 21 (21%) were receiving some
      form of drug prophylaxis, while 79% of patients were not taking any form of drug
      prophylaxis. Prophylaxis consisted of calcitriol (64%), alendronate (11%),
      calcitriol and calcium (7%), calcium alone (7%), alendronate and calcium (3%),
      etidronate and calcium (2%), alendronate, calcitriol and calcium (1%),
      alendronate and calcitriol (1%), and hormone replacement therapy (4%).
      Rheumatologists utilized both BMD testing and prophylactic treatment twice as
      often in patients taking chronic oral corticosteroid treatment than other
      specialty physicians. CONCLUSION: Compared to literature reports, the use of
      prophylaxis for corticosteroid induced osteoporosis was relatively high at this
      teaching hospital, with a surprisingly large number of patients receiving this
      treatment with no monitoring by BMD measurements.

PMID- 11296961
TI  - Gender differences in the relationships of serum uric acid with fasting serum
      insulin and plasma glucose in patients without diabetes.
AB  - OBJECTIVE: To explore gender differences in the relationship of serum uric acid
      levels with fasting serum insulin and fasting plasma glucose concentrations among
      an adult Chinese nondiabetic population in Kinmen, Taiwan. METHODS: A total of
      7,483 nondiabetic subjects (4,265 women, 3,218 men, aged 30 to 89 years) were
      involved in a community based epidemiologic study. Those with known or newly
      diagnosed diabetes were excluded. Overnight fasting blood samples were drawn for
      serum uric acid, glucose, insulin, lipid, and other biochemical measurements.
      Demographic and clinical variables including body mass index (weight/height2),
      waist-to-hip ratio, and blood pressure were measured and documented during face
      to-face interviews with structured questionnaires. RESULTS: Stratified analyses
      revealed that (1) serum uric acid levels were positively associated with
      hyperinsulinemia and HOMA-insulin resistance in both men and women after
      adjusting for hypertriglyceridemia, hypertension, obesity, and plasma glucose
      levels; and (2) serum uric acid levels were more strongly associated with
      hyperinsulinemia and plasma glucose levels in women than in men. CONCLUSION;
      Hyperuricemia was positively associated with hyperinsulinemia among patients of
      both sexes without diabetes. Elevated levels of uric acid should alert physicians
      to the possibility of insulin resistance. The serum uric acid level was
      associated with insulin resistance and plasma glucose levels more strongly in
      females than in males in our study population.

PMID- 11296962
TI  - Treatment of chronic gout. Can we determine when urate stores are depleted enough
      to prevent attacks of gout?
AB  - OBJECTIVE: To determine if lowering of serum uric acid (SUA) concentrations below
      6 mg/dl or longer duration of lowered SUA will result in depletion of urate
      crystals from the knee joints and prevent further attacks of gout. METHODS: A
      prospective study was initiated 10 years ago at Philadelphia VA Medical Center to
      attempt to maintain SUA levels of patients with crystal proven gout at < 6.0
      mg/dl. We recalled all 57 patients who were available during 1999. Patients were
      divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA <
      or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B
      patients and many in Group A. Aspirates were examined by polarized light
      microscopy for identification of crystals. RESULTS: There were no differences
      between the groups in age, sex, duration of gout, or serum creatinine. Group A (n
      = 38) had a mean of 6 attacks of gout for the recent year, those with tophi
      having the most frequent attacks. Among the 16 patients in this group who agreed
      to knee aspiration, monosodium urate (MSU) crystals were found in 14, although
      they were asymptomatic at the time. Nineteen patients (Group B) were able to
      maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them
      had no attack of gout for 2 or more years, with a mean of 1 attack in the last
      year for the whole group. Three patients in whom tophi were found did not have
      major flares of gout within the past year. Knee joint aspiration was done on 16
      asymptomatic patients. Seven (44%) still had MSU crystals present in their knees.
      Patients in this group who were taking prophylactic colchicine did not differ
      with respect to the character of synovial fluid from those who had discontinued
      it for up to several years, although the frequency of attacks was less in those
      who continued colchicine. CONCLUSION: A majority of patients were able to deplete
      urate crystal stores in their knee joint fluids when their SUA levels were kept
      to < or = 6 mg/dl for several years. The mechanisms for persistence in some
      patients, and whether such crystals have clinical implications, are not known.
      Patients with chronic gout need serum urate concentrations to be kept low to
      prevent further attacks.

PMID- 11296963
TI  - Abnormal sympathovagal balance in men with fibromyalgia.
AB  - OBJECTIVE: It is possible that there are differences in clinical manifestations
      between men and women with fibromyalgia syndrome (FM), especially in autonomic
      dysfunction; we assessed the interaction between the sympathetic and
      parasympathetic systems in postural change in men with FM using power spectral
      analysis (PSA) of heart rate variability (HRV), and investigated the pathogenesis
      of the orthostatic intolerance. METHODS: We studied 19 men with FM and 19
      controls matched for age and sex. A high resolution electrocardiogram was
      obtained in supine and standing postures during complete rest. Spectral analysis
      of R-R intervals was done by the fast Fourier transform algorithm. RESULTS: PSA
      of HRV revealed that men with FM at rest are characterized by sympathetic
      hyperactivity and concomitantly reduced parasympathetic activity. During postural
      changes, male patients demonstrated an abnormal sympathovagal response. These
      results provide the physiological basis for the orthostatic intolerance in men
      with FM. CONCLUSION: This report of autonomic dysfunction in men with FM revealed
      an abnormal autonomic response to orthostatic stress. This abnormality may have
      implications regarding the symptoms of FM.

PMID- 11296964
TI  - Fibromyalgia and chronic widespread pain in patients with inflammatory bowel
      disease: a cross sectional population survey.
AB  - OBJECTIVE: To assess the prevalence of fibromyalgia (FM) and chronic widespread
      pain (CWP) in a population based cohort of patients with inflammatory bowel
      disease (IBD). METHODS: Patients in a prospective survey on newly diagnosed IBD
      were, 5 years after study entry, invited to a clinical examination including the
      investigation of musculoskeletal manifestations. A total of 521 patients were
      examined, corresponding to 80% of surviving cases with definite diagnoses of
      ulcerative colitis (UC) and Crohn's disease (CD). The diagnoses of FM and CWP
      strictly followed the American College of Rheumatology classification criteria of
      1990. RESULTS: At clinical examination, FM was diagnosed in 18 patients (3.5%),
      3.7% with UC and 3.0% with CD. The prevalence was 6.4% in females and 0.4% in
      males. Thirty-eight patients (7.3%) had CWP (8.5% with UC; 4.8% with CD). The
      female:male ratio was 27:3 in the UC group and 8:0 in CD. In 19 patients (50%),
      CWP occurred after onset of IBD. No correlation with the extent of intestinal
      inflammation and the occurrence of FM and CWP was found. CONCLUSION: The
      prevalences of FM and CWP in patients with IBD were similar to those of the
      general population. There were no differences in prevalence of FM and CWP between
      UC and CD. Chronic idiopathic inflammation of the intestine does not appear to
      predispose to chronic widespread pain.

PMID- 11296965
TI  - Antibodies against serotonin have no diagnostic relevance in patients with
      fibromyalgia syndrome.
AB  - OBJECTIVE: To determine the prevalence and potential diagnostic relevance of
      autoantibodies against serotonin, thromboplastin, and ganglioside Gm1 in patients
      with fibromyalgia syndrome (FM). METHODS: Sera from 203 patients with FM and 64
      pain-free control subjects were analyzed with enzyme immunoassays. Clinical and
      psychometric data of the patients were analyzed for the presence or absence of
      autoantibodies. RESULTS: Compared with control subjects patients with FM had a
      significantly higher prevalence of autoantibodies against serotonin (20% vs 5%; p
      = 0.003) and thromboplastin (43% vs 9%; p < 0.001), but not against ganglioside
      Gm1 (15% vs 9%; p = 0.301). Differences in autoantibody prevalence between
      controls and FM patients were not related to age or sex. No association was found
      between autoantibody pattern and clinical or psychometric data, e.g., pain,
      depression, pain related anxiety, and activities of daily living. CONCLUSION:
      There is an elevated prevalence of antibodies against serotonin and
      thromboplastin in patients with FM. The pathophysiological significance of this
      finding is unknown. Calculation of positive predictive values of antiserotonin
      antibodies shows that measurement of these antibodies has no diagnostic
      relevance.

PMID- 11296966
TI  - Comparison of viral antibodies in 2 groups of patients with fibromyalgia.
AB  - OBJECTIVE: The etiologies of fibromyalgia (FM) are unknown. In some cases an
      acute onset following a flu-like episode is described; in other cases patients
      report slowly developing disease. We previously found increased prevalence of
      enterovirus IgM antibodies in patients with acute onset of FM compared to healthy
      controls. We looked for differences in antimicrobial IgM antibodies in acute
      versus nonacute onset FM. METHODS: Two well defined, comparable groups of
      patients with FM (acute 19, nonacute 20) were studied for antibodies in serum to
      an array of viruses including IgM antibodies. RESULTS: In most viruses no IgM
      antibodies were found. However, about 50% of the patients with acute FM onset had
      IgM antibodies against enterovirus compared to only 15% of the slow onset
      patients. CONCLUSION: The higher prevalence of IgM antibodies against enterovirus
      in patients with acute onset of FM may indicate a difference in the etiology or
      the immune response in these patients.

PMID- 11296967
TI  - Risk factors for development of lower limb pain in adolescents.
AB  - OBJECTIVE: Although many clinicians believe high growth leads to inflexibility,
      which may lead to lower extremity pain, the only prospective data suggest growth
      is unrelated to flexibility. However, it is still possible that growth and/or
      flexibility are related to pain even if they are not related to each other. We
      investigated the incidence of leg pain in adolescents to determine whether high
      growth spurt and/or poor flexibility are risk factors for the development of
      lower extremity pain. METHODS: Repeated measures, prospective cohort study of
      urban high school students aged 12-18. Subjects were measured at baseline and at
      6 and 12 months for flexibility of hamstrings and quadriceps and with the sit-and
      reach test. Participants completed a detailed questionnaire on recreational
      activity, occupational activities, psychosocial variables, and musculoskeletal
      pain. RESULTS: Poor hamstring flexibility (odds ratio 0.99, confidence interval
      0.97-1.01), poor quadriceps flexibility (OR 1.01, CI 0.99-1.03), poor sit-and
      reach flexibility (OR 0.99, CI 0.99-1.01), and growth (OR 0.93, CI 0.50-1.71)
      were not related to the development of lower extremity pain. There was an
      association between lower extremity pain and occupational activities (OR 2.08, CI
      1.45-2.98) and poor mental health (per 1 SD change, OR 1.41, CI 1.19-1.67).
      CONCLUSION: Neither growth nor flexibility is related to the development of lower
      extremity pain in adolescents. A poor mental health score and occupational
      activities may be associated with the development of lower extremity pain.

PMID- 11296968
TI  - Lipodystrophy in patients with juvenile dermatomyositis--evaluation of clinical
      and metabolic abnormalities.
AB  - OBJECTIVE: Lipodystrophy and associated metabolic abnormalities are being
      increasingly recognized as complications of juvenile dermatomyositis (JDM). We
      investigated the prevalence of lipodystrophy and the extent of metabolic
      abnormalities related to lipoatrophic diabetes mellitus in patients with JDM.
      METHODS: Twenty patients with JDM were evaluated for evidence of lipodystrophy
      and associated lipoatrophic diabetes mellitus. All patients underwent clinical
      assessment, laboratory investigations, and metabolic studies (oral glucose
      tolerance test, lipid studies, insulin antibodies). RESULTS: We found clinical
      evidence of lipodystrophy and lipoatrophic diabetes mellitus in 4 of 20 patients
      with JDM and metabolic abnormalities known to be associated with lipodystrophy in
      another 8 patients. The 20 patients with JDM were categorized as follows: Group 1
      (Patients 1-4) consisted of patients with lipodystrophy and either diabetes
      mellitus (2 patients) or impaired glucose tolerance (2 patients); Group 2
      (Patients 5-12): no lipodystrophy but abnormal glucose and/or lipid studies;
      Group 3 (Patients 13-20): no lipodystrophy and no abnormalities of glucose and
      lipid studies. CONCLUSION: We found 25% of patients with JDM have lipodystrophy,
      and 50% present with hypertriglyceridemia and insulin resistance. Screening for
      metabolic abnormalities in JDM should be included in routine followup because of
      the effect of lipodystrophy on longterm prognosis.

PMID- 11296969
TI  - Primary angiitis of the central nervous system in children: 5 cases.
AB  - We describe 5 children who meet criteria for primary angiitis of the central
      nervous system (PACNS). All patients presented with headache and/or focal
      neurologic deficits and exhibited clinical and/or radiographic evidence of
      disease progression. Two patients had disease progression prior to combined
      treatment with cyclophosphamide and corticosteroids; one progressed while
      receiving intravenous cyclophosphamide and stabilized after a change to daily
      oral dosing; one progressed after discontinuing therapy after less than 12 months
      and improved after retreatment; and one progressed on steroid therapy alone but
      was lost to followup. Children who have frequent or severe headaches or focal
      neurologic deficits should be carefully evaluated and those meeting criteria for
      PACNS should be treated aggressively.

PMID- 11296970
TI  - Cricoarytenoid arthritis with rheumatoid arthritis and systemic lupus
      erythematosus.
AB  - A 56-year-old woman with rheumatoid arthritis (RA) suddenly developed severe
      respiratory distress and laryngeal stridor, which required endotracheal
      intubation. She had had RA for 12 years, which had been controlled well with
      prednisolone (3 mg/day) at the orthopedic clinic. Laryngoscopy revealed
      cricoarytenoid arthritis. She was finally diagnosed as having overlap syndrome
      with RA and systemic lupus erythematosus. She was given high dose corticosteroids
      that improved her clinical symptoms and laryngoscopic findings. She represents
      the first patient with overlap syndrome who developed an acute airway obstruction
      due to cricoarytenoid arthritis.

PMID- 11296971
TI  - Lumbar pannus presenting as cauda equina syndrome in a patient with longstanding
      rheumatoid arthritis.
AB  - Relatively little attention has been paid to lumbar spine involvement in
      rheumatoid arthritis (RA), and indeed it is generally considered to be an
      uncommon and usually clinically minor manifestation of the disease. We describe a
      case of acute right lower extremity weakness secondary to compression of multiple
      lumbar nerve roots by a large interforaminal rheumatoid pannus, and review the
      literature on this complication and other lumbar spine involvement in RA.

PMID- 11296972
TI  - Localized neurological necrotizing vasculitides. Three cases with isolated
      mononeuritis multiplex.
AB  - Localized vasculitic neuropathies are increasingly reported. We describe 3 cases
      of peripheral neuropathy with necrotizing vasculitis confined to nerves and
      muscles without systemic involvement. These neuropathies were severe and
      relapsing, in contrast to a usually benign prognosis. Our cases appear to be
      isolated vasculitic neuropathies, with vasculitis strictly limited to the
      peripheral neuromuscular system without nonspecific clinical and/or biological
      systemic involvement.

PMID- 11296973
TI  - Relapsing polychondritis and erythema elevatum diutinum: an unusual association
      refractory to dapsone.

PMID- 11296974
TI  - Ninth International Conference on Behcet's Disease, Seoul, Korea, May 27-29,
      2000.

PMID- 11296975
TI  - Issues of consensus and debate for economic evaluation in rheumatology.
AB  - We report initial attempts at developing standards for the conduct of economic
      evaluations in rheumatology. We surveyed 25 clinicians and economists with an
      interest in rheumatology regarding the design and reporting of economic
      evaluations, with particular reference to 4 clinical scenarios relating to
      treatment for rheumatoid arthritis, osteoarthritis, and osteoporosis. The results
      demonstrated widespread agreement on a number of methodological issues such as
      statement of funding source, perspective, discounting, and allowance for
      uncertainty. However, there was lack of consensus over clinical variables
      including sources of data for efficacy estimates, specific clinical outcomes,
      methods of assessing quality of life, and choice of comparators. Some of the
      disagreement reflects lack of consensus in current general methodological
      guidelines. Consensus regarding the disease-specific clinical variables is
      crucial to standardizing analysis and facilitating comparisons within clinical
      scenarios.

PMID- 11296976
TI  - Rating of arthritis health states by patients, physicians, and the general
      public. Implications for cost-utility analyses.
AB  - We elicited preferences for 2 arthritis health states (mild and severe) using
      visual analog scales, time tradeoff, and standard gamble by interviewing 104
      individuals from the general public, 51 patients with rheumatoid arthritis, and
      43 health professionals. The health scenarios were based on attributes described
      in a health status classification instrument, the EuroQol (EQ-5D). In addition,
      we compared the ratings in our survey with those obtained for the same scenarios
      by one of the scoring algorithms used for the EQ-5D (York weights). Statistically
      significant differences were observed in the ratings of the health scenarios,
      mostly for the severe vignette. Most of the variability was related to the method
      employed. The cost-utility ratio for a hypothetical intervention varied according
      to the method employed to determine the utility of the health states, from
      $15,000 to $111,000 US per quality adjusted life year (QALY). Patient derived
      weights resulted in cost-utility ratios that ranged from $39,000 to $222,000. Our
      findings show that the methodology used to elicit and analyze utilities can have
      substantial implications in the economic evaluation of interventions for patients
      with RA.

PMID- 11296977
TI  - Development of a matrix of cost domains in economic evaluation of rheumatoid
      arthritis.
AB  - The aim of our study was to comprehensively review and critically appraise the
      cost domains used in economic evaluations of the rheumatic diseases and to use
      this information to propose standardization of cost domains. The literature
      search identified 210 abstracts, 32 of which included original cost data. The
      listed cost categories were grouped into 3 major areas: (direct) health care
      costs, other (direct) disease related costs, and productivity costs (indirect
      costs). The number of individual cost categories was reduced by considering the
      following criteria: (1) inclusion of all relevant cost domains; (2) avoidance of
      double counting; (3) summarizing of related categories under one representative
      heading; (4) feasibility of level of aggregation. After adjustment for synonymous
      labeling, 38 cost categories remained. The subsequent development of a
      classification scheme of cost categories led to a set of 19 separate cost domains
      including 7 outpatient, 3 inpatient, 6 other disease related, and 3 productivity
      cost domains. This literature review indicates that cost assessment in economic
      evaluations in rheumatoid arthritis lacks standardization. A preliminary scheme
      to categorize cost assessment in rheumatic conditions is presented. The adoption
      of standards for economic evaluation would greatly facilitate national and
      international comparisons.

PMID- 11296978
TI  - Cost assessment instrument in rheumatology: evaluation of applied instrument
      characteristics.
AB  - We compared the major characteristics of internationally applied cost assessment
      instruments (CAI) in rheumatic conditions. Fifteen utilization questionnaires
      were identified and assessed using a structured approach. The forms differed
      considerably with respect to applied characteristics: length (3-113 items),
      recall period (between 1 week and 1 year), format (2 interview, 13 self
      administered), response categories, cost units (physical vs monetary), and cost
      domains covered. While all included a gross assessment of outpatient and
      inpatient costs, the level of disaggregation differed. Only a few CAI included an
      assessment of other direct disease related costs (e.g., home remodeling or home
      health care services) and out-of-pocket expenditure. Productivity costs were
      included in all but 2 CAI. Efforts to further standardize the applied CAI should
      (1) be based on sound psychometric data, (2) define a required core set of cost
      domains covered, (3) discriminate between generic and relevant disease related
      cost components, and (4) examine the feasibility of developing international
      standards for cost data.

PMID- 11296979
TI  - OMERACT: economic evaluations and health policy.
AB  - The aim of this paper is to review how decisions are made about the delivery of
      health care. Limited resources and increasing health care costs have resulted
      internationally in a growing necessity to understand the economic consequences of
      health care delivery. Rheumatology remains underfunded because the societal
      impact of chronic conditions is not well appreciated in the current policy-making
      context. Although health policy development varies with the care delivery
      systems, economic evaluation can be used for incremental system-wide reform to
      prioritize spending across multiple diseases and interventions. It is important
      to understand how policy and funding decisions are made in order to see how they
      might be influenced.

PMID- 11296981
TI  - Fibromyalgia and the law.

PMID- 11296980
TI  - OMERACT 5 Economics Working Group: summary, recommendations, and research agenda.

PMID- 11296982
TI  - Fibromyalgia and the law.

PMID- 11296983
TI  - Fibromyalgia and the law.

PMID- 11296984
TI  - The epidemiology of psoriatic arthritis.

PMID- 11296985
TI  - Extensive pigmentation secondary to minocycline treatment of rheumatoid
      arthritis.

PMID- 11296986
TI  - Termination of disease modifying antirheumatic drugs in psoriatic arthritis.

PMID- 11296987
TI  - Beaver fever--a rare cause of reactive arthritis.

PMID- 11296988
TI  - Introduction. Vasculitis.
AB  - The vasculitides commonly create diagnostic and management problems, and a biopsy
      diagnosis of vasculitis usually does not stand alone in the proper medical
      management of a patient. Indeed, a conclusive diagnosis usually cannot be made
      without correlation with the patient's clinical history, physical findings,
      and/or angiographic findings. Nonetheless, a definitive diagnosis depends on
      histologic examination because few vasculitic syndromes have specific clinical
      and laboratory findings. Moreover, the histopathologic diagnosis depends on
      pathologist experience, tissue selection, sample size, chronologic age of the
      biopsied lesion(s), and effects of prior treatment. In this issue of Seminars in
      Diagnostic Pathology the important systemic vasculities are reviewed and updated.
      These include: polyarteritis nodosa, microscopic polyangiitis (microscopic
      polyarteritis), cutaneous leukocytoclastic vasculitis, Wegener's granulomatosis,
      giant-cell vasculitides, localized vasculitis, and angiocentric lymphomas
      (lymphomatous vasculitis).

PMID- 11296989
TI  - Polyarteritis nodosa.
AB  - Polyarteritis nodosa is one of the earliest forms of systemic vasculitis
      described. It is characterized by segmental necrotizing arterial lesions
      affecting medium-sized and small-sized arteries. Active necrotizing lesions are
      frequently associated with chronic reparative lesions. Current convention would
      exclude patients with necrotizing glomerular lesions from this category. An
      aneurysm may form when the arterial wall is sufficiently weakened by the
      necrotizing process. Any organ may be affected; however, pulmonary involvement is
      very uncommon. Significant potential exists for end organ injury resulting from
      ischemia, infarcts, and hemorrhage. A variety of other primary systemic
      vasculitidies, secondary forms, such as connective tissue disease associated, and
      organ limited forms, have been identified that may exhibit similar arterial
      lesions including aneurysm formation. Establishing a definitive diagnosis of
      polyarteritis nodosa is therefore challenging, and mandates dialogue between the
      pathologist and the clinician primed with pertinent clinical and laboratory data.
      Fortunately, with early diagnosis and aggressive treatment with cytotoxic agents,
      the prognosis of polyarteritis nodosa has substantially improved.

PMID- 11296990
TI  - Giant-cell vasculitides.
AB  - Although many of the vasculitides within the classification of the American
      College of Rheumatology can have a component of granulomatous inflammation with
      giant cells, two (ie, giant-cell [temporal] arteritis and Takayasu arteritis) are
      characterized by infiltrates that are dominated by granulomatous and/or giant
      cell-containing inflammation. Furthermore, granulomatous and/or giant-cell
      dominant infiltrates can characterize disseminated giant-cell arteritis,
      granulomatous vasculitis of the central nervous system, localized giant-cell
      arteritis, mesenteric inflammatory veno-occlusive disease, primary cutaneous
      phlebitis, and giant-cell phlebitis of mesenteric veins and/or omentum. Like the
      other systemic vasculitides, there is considerable clinicopathologic overlap
      between these giant-cell vasculitides. Indeed, they are likely closely related,
      but how they specifically relate to each other is not clear. Their accurate
      diagnosis is important; because serious morbidity and even death may occur, if
      proper treatment is delayed or if excessive immunotherapy is given.

PMID- 11296991
TI  - Microscopic polyangiitis (microscopic polyarteritis).
AB  - Microscopic polyangiitis ("microscopic polyarteritis") is a form of necrotizing
      small vessel vasculitis that most often affects venules, capillaries, arterioles,
      and small arteries, although it occasionally involves medium-sized arteries.
      Microscopic polyangiitis is a more appropriate name than microscopic
      polyarteritis because some patients have no evidence for arterial involvement.
      The absence or paucity of immunoglobulin localization in vessel walls
      distinguishes microscopic polyangiitis from immune complex mediated small vessel
      vasculitis, such as Henoch-Schonlein purpura and cryoglobulinemic vasculitis.
      Clinical, epidemiological, and pathologic differences warrant the separation of
      microscopic polyangiitis from polyarteritis nodosa on the basis of involvement of
      capillaries and venules by the former but not the latter. Pauci-immune
      necrotizing and crescentic glomerulonephritis, and hemorrhagic pulmonary
      capillaritis are common in patients with microscopic polyangiitis. Microscopic
      polyangiitis is the most common cause for pulmonary-renal vasculitic syndrome.
      The vasculitis in patients with microscopic polyangiitis is pathologically
      indistinguishable from the vasculitis of Wegener's granulomatosis and Churg
      Strauss syndrome. Granulomatous inflammation distinguishes Wegener's
      granulomatosis from microscopic polyangiitis. Asthma and eosinophilia distinguish
      Churg-Strauss syndrome from microscopic polyangiitis. Microscopic polyangiitis,
      Wegener's granulomatosis, and Churg-Strauss syndrome are all associated with
      circulating antineutrophil cytoplasmic autoantibodies.

PMID- 11296992
TI  - Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is currently categorized as one of the
      antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitides
      distinguished by its predilection to affect the upper and lower respiratory
      tracts and kidneys clinically and histologically by the presence of necrosis,
      granulomatous inflammation, and vasculitis. However, small biopsies, especially
      from the head and neck region, often lack all these diagnostic histologic
      findings. Other common histologic features of WG include microabscesses and
      scattered multinucleated giant cells in a highly inflammatory background. Support
      from distinctive clinical setting or positive cytoplasmic (C)-ANCA testing may
      help establish the diagnosis of WG in cases lacking all the typical pathologic
      findings. The histopathologic differential diagnosis of WG includes nonspecific
      inflammatory conditions, infections, angiocentric lymphomas, collagen vascular
      diseases, and other forms of angiitis and granulomatosis. The prognosis of WG has
      dramatically improved from the 18% 5-month survival rate before the era of
      immunosuppressive therapy to the current remission rate of over 75% with a
      regimen of cyclophosphamide and glucocorticoids. A significant rate of relapse
      and profound disease- and/or treatment-related morbidity still occur. The cause
      of WG remains unknown, but circumstantial evidences suggest the potential roles
      of ANCA and infection in the pathogenesis.

PMID- 11296993
TI  - The cutaneous neutrophilic vascular injury syndromes: a review.
AB  - The skin manifestations of vasculitis reflect injury by all of the classic immune
      reactions of Gell and Coombs. As the skin affords a window of opportunity for the
      clinician to obtain tissue for diagnostic purposes in patients with systemic
      vasculitic syndromes, a thorough understanding of the dermatopathologic
      manifestations of those systemic diseases is a considerable asset to the
      practicing pathologist. This review focuses on those systemic diseases that can
      provoke a small vessel neutrophilic injury pattern in the skin and provides clues
      by which these diseases can be separated from each other and from their innocuous
      mimics in which cutaneous vascular injury is the only significant consequence.

PMID- 11296994
TI  - Localized vasculitis.
AB  - The mechanisms of vasculitis are poorly understood, but involve immune-mediated
      destruction of vessel walls. Depending on the syndrome, there is significant
      variability in the size and types of vessels involved, as well as the nature of
      the inflammatory infiltrate. In addition, there is a wide variation from 1
      patient to another in the extent of involvement throughout the vascular tree. In
      some forms of vasculitis that are histologically indistinguishable from systemic
      syndromes, the inflammatory process appears to be isolated, or localized to a
      single site or organ. In most such cases, especially in localized forms of
      necrotizing polyarteritis, the prognosis is far better than for corresponding
      systemic vasculitides, and progression to systemic disease is unusual even
      without immunosuppressive treatment. However, for other types of vasculitic
      syndromes, especially Wegener's granulomatosis and antineutrophil cytoplasmic
      autoantibody-related vasculitis, presentation as a localized process warrants
      immediate treatment and may herald a prolonged, if relatively limited, disease.
      This article outlines the clinical and pathologic features of the vasculitis
      syndromes that may be localized at the time of diagnosis, and emphasizes which
      features are associated with progression to systemic disease.

PMID- 11296995
TI  - Angiocentric lymphomas (lymphomatous vasculitis).
AB  - Angiocentric lymphomas are a heterogeneous spectrum of hematolymphoid
      malignancies that share a particular histologic characteristic, namely, an
      angiocentric or perivascular growth pattern. They include a variety of T-, B-,
      and natural killer-cell derived lymphomas that digress in many clinicopathologic
      features, immunophenotype, and prognosis. The term angiocentric lymphomas was
      initially used to refer to natural killer and natural killer-like T-cell
      lymphomas that show a prominent angiocentric growth pattern. With better
      immunophenotypic and molecular characterization together with evolving knowledge
      regarding their biology and pathogenesis, these lymphomas have now been
      reclassified. Apart from morphology, many features pertinent to the diagnosis of
      natural killer and natural killer-like T-cell lymphomas are shared by other
      peripheral T-cell and B-cell lymphomas, and by a subset of leukemias. The salient
      clinicopathologic features of natural killer and natural killer-like T-cell
      lymphomas together with the inherent difficulty of their identification and an
      integrated approach to their diagnosis are outlined in this article.

PMID- 11296996
TI  - Exercise training in asthma.
AB  - Asthma is a chronic disease that is often limiting the exercise capacity.
      Rehabilitation programs are recommended and widely applied in asthmatic patients,
      and exercise prescription is a keystone of these programs. The impairment of
      exercise performance in asthmatics, the role of exercise training in such
      patients, the mechanisms of its beneficial effects and the suggested programs are
      discussed in a review, accordingly to the current evidence and available data in
      scientific literature. Exercise performance is impaired in most asthmatics. There
      is no conclusive evidence that asthma may involve a ventilatory limitation to
      exercise. The lesser fitness in asthmatics seems mainly due to inactivity and
      sedentary lifestyle. Exercise induced asthma (EIA) is a significant problem, and
      the best approach to minimise its effects on exercise capacity is prevention.
      Exercise training has been proved to have health-related benefits and to improve
      the quality of life. There is substantial evidence that exercise training
      increases exercise performance and fitness in asthmatics. It is still unclear
      whether physical training improves pulmonary function and bronchial
      responsiveness. Since asthma ranges widely, exercise prescription varies for each
      patient. The proper selection of the patients and the choice of exercise programs
      are the steps required. Accordingly with the severity of the disease, exercise
      strategies may range from sports activities to, when the disease is severe,
      inpatient hospital programs that overlap with COPD rehabilitation. Further
      research to clarify some aspects (effects on pulmonary function and EIA,
      outcomes, cost-benefit relationship) is necessary.

PMID- 11296997
TI  - A decade of aerobic endurance training: histological evidence for fibre type
      transformation.
AB  - BACKGROUND: Researchers employing a variety of training methods have demonstrated
      a fast-to-slow fibre transformation in animal skeletal muscle. The observation as
      to whether this occurs in exercise trained humans is limited and equivocal.
      METHODS:  EXPERIMENTAL DESIGN: to examine this issue, skeletal muscle from seven
      subjects who had participated in a decade or more of high intensity aerobic
      training (DT) and six nontrained (NT) subjects was obtained by muscle biopsy from
      the vastus lateralis muscle (VL) and subjected to a modified myofibrillar ATPase
      technique to identify muscle fibre types. Muscle tissue was histochemically
      treated by exposure to an alkaline preincubation (pH 9.9), an acid preincubation
      (pH 4.3 or 4.6) and the formate-KCI preincubation buffer (pH 4.54), previously
      employed in animal studies. RESULTS: The formate-KCl preincubation medium
      identified all major fibre types at a single pH in human subjects. The percentage
      of type I fibres in DT was 70.9% vs 37.7% in NT (p<0.01), while the type IIa
      fibres in DT (25.3%) was much lower (p<0.01) than NT (51.8%). Surprisingly, type
      IIa fibres in the DT group displayed lesser oxidative staining intensity (p<0.01)
      than type IIa fibres from the NT group. Mean cross-sectional area of type I
      fibres for DT (6233.9+/-1421.7 microm2) was greater (p<0.05) than either type I
      (5746.8+/-1135.2 microm2) or II (5693.5+/-1214.6 microm2) from NT. CONCLUSIONS:
      The results revealed that endurance training may promote a transition from type
      II to type I muscle fibre types and occurs at the expense of the type II fibre
      population.

PMID- 11296998
TI  - Energy cost of treadmill running in non-trained females differing in body fat.
AB  - BACKGROUND: The energy demands of movement may be characterised by the energy
      cost C, which indicates how much energy is needed to carry a body mass of 1 kg
      over a distance of 1 m. It is generally accepted that the lower C represents a
      lesser amount of mechanical work executed with the same efficiency. The purpose
      of this study was to assess the influence of body fat on energy cost of running
      in healthy non-trained females. METHODS: Energy cost of running (C) was
      determined on the treadmill in a group of healthy non-trained females (N=63, mean
      age=39.+/-10.2 years, body mass=64.6+/-5.5 kg, height= 166.2+/-5.7 cm, VO2max.kg(
      1)=35.0+/-3.6 ml.kg(-1)min(-1)), differing significantly in the percentage of
      body fat (18.9-30.2%), assessed by the 10 skinfold measurements. RESULTS: Mean
      value of C was 3.97+/-0.07 J.kg(-1)m(-1). The lowest values of C were found in
      subjects with the lowest %BF (C ranged from 3.81 to 4.06 J.kg(-1).m(-1)). There
      is a significant positive correlation between C and %BF [C (J.kg(-1).m(-1))=
      0.0185*%BF (%) + 3.5090; r=0.7805; p<0.001; r2=0.6091], C and body mass (BM) [C
      (J.kg(-1).m(-1)) = 0.0083*BM (kg) + 3.4384; r=0.6176; p<0.001; r2 = 0.3814], and
      C and free fat mass (FFM) [C (J.kg(-1).m(-1))=0.0087*FFM (kg) + 3.5543; r=0.3521;
      p<0.05; r2=0.1240]. There is a negative correlation between C and VO2max.kg(-1)
      [C (J.kg(-1).m(-1))=-0.0181* VO2max.kg(-1) (ml.kg(-1).min(-1)) +4.6071; r=
      0.8810; p<0.0001; r2=0.7761], and VO2max.kg(-1) and %BF [VO2max.kg(-1) (ml.kg(
      1).min(-1)) =-0.8401* %BF(%) + 54.1021; r=-0.7142; p<0.0001; r2=0.5101].
      CONCLUSIONS: From the collected data for untrained females we may conclude:
      first, the higher the training state (VO2max.kg(-1)), the lower the energy cost
      of running. Second, the energy cost of running C increases with the increase in
      body mass, %BF and FFM. Third, the training state decreases (VO2max.kg(-1)) with
      the increase in %BF.

PMID- 11296999
TI  - Energy expenditure during walking and jogging.
AB  - BACKGROUND: The aim of this investigation was to compare the physiological and
      subjective responses during treadmill walking and jogging at several
      corresponding speeds in physically active young women. METHODS:  EXPERIMENTAL
      DESIGN: Maximal oxygen uptake was determined during a continuous treadmill test
      to exhaustion. The walking protocol consisted of treadmill walking for five min
      at each of the following speeds: 4.0, 5.6, 7.2, 8.0, 8.8, 9.6 and 10.4 km.hr(-1).
      The jogging protocol consisted of treadmill walking for five min at 4.0, and 5.6
      km.hr(-1) and treadmill jogging for five min at each of the following speeds:
      7.2, 8.0, 8.8, 9.6 and 10.4 km.hr(-1). SETTING: This research was performed at
      Washington University School of Medicine. PARTICIPANTS: Fifteen healthy women
      (mean+/-SE, age; 26.9+/-1.4 yrs, BMI; 22.5+/-0.70, VO2max; 41.9+/-1.9 ml.hr(
      1).min(-1)) performed a maximal treadmill exercise test, a walking test and a
      jogging test. RESULTS: The rate of oxygen consumption, calculated energy
      expenditure per distance (kJ.hr(-1).mile(-1)) and heart rates were significantly
      higher during walking compared to jogging at treadmill speeds > or =8.8 km.hr(
      1). Plasma lactate concentration and respiratory exchange ratio were
      significantly higher at treadmill speeds > or =8.0 km.hr(-1) during walking as
      compared to jogging. Subjects subjectively rated their exertion during walking as
      being significantly greater when compared to jogging across the range of
      overlapping treadmill speeds. CONCLUSIONS: These findings demonstrated that
      walking at speeds > or =8.0 km.hr(-1) resulted in rates of energy expenditure
      that were as high or higher than jogging at the same speeds. Also, the higher
      rates of energy expenditure during walking as compared to jogging at speeds
      greater than 8.0 km.hr(-1) were associated with higher heart rates, RER, RPE and
      plasma lactate response.

PMID- 11297000
TI  - Physiological responses during two types of exercise performed on land and in the
      water.
AB  - BACKGROUND: The purpose of this study was to compare heart rate (HR) and oxygen
      consumption (VO2) for similar upright exercises performed on land (LN) and in
      water (WA). METHODS:  SETTING AND PARTICIPANTS: apparently healthy, females
      (n=12; 20.0+/-1.6 yrs) completed legs only, and arms and legs exercises in WA
      (30.0+/-0.0 C) and LN (273+/-2.1 C). INTERVENTION: exercise cadence/intensity
      increased each 3 min to evoke comparable, relative exercise HRs on LN and WA for
      each participant. EXPERIMENTAL DESIGN: three-way (Environment X Type of exercise
      X Intensity) repeated measures ANCOVAs with pace as the covariate were calculated
      for VO2 and HR. Linear and multiple regressions were determined. MEASURES: HR,
      VO2, and pace were measured for the final steady state minute of all levels of
      the independent variables. Resting HR and blood pressure were measured pre- and
      postexercise. RESULTS: There was a significant main effect due to environment for
      VO2. There was not a significant main effect of environment for HR because the
      pace of exercise was adjusted in the water so that similar "relative" workloads
      (ie., intensities, assessed from monitoring HR) were given to each participant.
      HR and VO2 were greater for arms and legs exercise, and were greater at increased
      exercise intensities. No interactions were present among the independent
      variables. When WA exercise was performed at HR levels comparable to HR during
      land exercise, WA VO2 were 2-6 ml.kg(-1).min(-1) greater than LN VO2.
      CONCLUSIONS: Participants were at a >VO2 in WA, but would not know this from
      monitoring their HRtraining. During WA exercise, the HR-VO2 regression line was
      shifted to the right. Results of the regression analyses showed that VO2 was a
      significant predictor of HR. HRtraning predicted using these equations indicated
      that HRtraining during upright water exercise should be decreased by
      approximately 7-13 beats.min(-1) for legs only water exercise and arms/legs water
      exercise to attain intensities comparable to LN exercise.

PMID- 11297001
TI  - Differences in muscle cross-sectional area and strength between elite senior and
      college Olympic weight lifters.
AB  - BACKGROUND: The purpose of this study was to investigate the profiles of muscle
      cross-sectional area (CSA) and strength capability in relation to lifting ability
      in Olympic weight lifters. METHODS: The subjects were 8 elite senior lifters
      (ESL, age=25.2+/-1.3 years, height=1.64+/-0.03 m, mass=68.6+/-4.2 kg, mean+/-SEM)
      and 9 college lifters (CL, 20.8+/-0.3 years, 1.67+/-0.03 m, 70.53.4 kg) whose
      predetermined weight classes were within the same range. The CSAs of elbow or
      knee extensor and elbow or knee flexor muscles were measured using a B-mode
      ultrasound apparatus. Concentric and eccentric maximal voluntary forces were
      determined with an isokinetic dynamometer at a constant velocity of 1.05 rad/sec.
      RESULTS: The best score of the total mass lifted in the snatch and the clean and
      jerk lifts was significantly higher in ESL than in CL even in terms of per unit
      of fat-free mass. There were no significant differences between the two groups in
      fat-free mass, muscle CSA and force values with the exception that ESL compared
      to CL showed significantly greater force in concentric knee flexion. However, the
      ratios of force to muscle CSA (F/CSAs) in concentric and eccentric elbow
      extensions, eccentric knee extension and concentric knee flexion were
      significantly higher in ESL than in CL. CONCLUSIONS: The present results
      indicated that the magnitude of muscular development in limbs was similar in
      elite senior and college lifters whose predetermined weight classes were within
      the same range. As compared to college lifters, however, elite senior lifters had
      a higher F/CSA in specific muscle action modes, which might relate to the optimal
      execution of the Olympic lifts.

PMID- 11297002
TI  - Perceived exertion during isometric quadriceps contraction. A comparison between
      men and women.
AB  - BACKGROUND: 1) To examine the validity and accuracy of the CR-10 scale for
      evaluating perceived exertion, and 2) to assess gender differences in perceived
      exertion across different levels of contraction intensity. METHODS:  EXPERIMENTAL
      DESIGN: cross-sectional, comparative design. SETTING: Human Performance and
      Fatigue Laboratory, Eastern Washington University. SUBJECTS: 30 healthy, college
      age volunteers (15 males, 15 females). MEASURES: All subjects were assessed for
      isometric torque and perceived exertion of the quadriceps femoris muscles, via
      the CR-10 scale. One low anchor was applied under resting conditions with the
      knee flexed to 60 degrees, and a high anchor was applied during a maximal
      voluntary muscle contraction (MVC). SUBJECTS performed five-second isometric
      contractions equivalent to 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% of
      their MVC, in a random order, and were assessed for perceived exertion by
      visually observing the CR-10 scale. One sample "t"-tests and 95% confidence
      intervals were calculated for perceived exertion at each relative torque level. A
      single factor ANOVA with repeated measures was performed across al levels of
      exercise intensity. Linearity for perceived exertion was assessed via regression
      analysis. RESULTS: Perceived exertion at each exercise intensity were as follows:
      10%: 1.87+/-1.14, 20%: 2.43+/-1.19, 30%: 3.5+/-1.36, 40%: 3.97+/-1.52, 50%:
      4.73+/-1.28, 60%: 5.53+/-1.28, 70%: 6.73+/-1.62, 80%: 7.57+/-1.72, and 90%: 8.6+/
      1.52. The increase in perceived exertion across the intensity spectrum was found
      to fit both linear and quadratic trends. There were no gender differences in
      perceived exertion across all levels of exercise intensity. CONCLUSIONS: The
      findings demonstrate that the CR-10 scale closely approximates perceived exertion
      of the quadriceps femoris muscles during sub-maximal, static contractions, and is
      not gender specific.

PMID- 11297003
TI  - Training of junior rowers before world championships. Effects on performance,
      mood state and selected hormonal and metabolic responses.
AB  - BACKGROUND: Few data have been published on training of competitive athletes and
      about metabolic, hormonal and psychological reactions to overreaching (transient
      over-training) and tapering in successful athletes. METHODS: Training was
      recorded and effects on mood state and metabolic and hormonal responses were
      examined in 10 rowers and spares of the coxed eight during preparation for the
      World Championships 1995. Mood state was determined using the Recovery-Stress
      Questionnaire for Athletes. Resting morning blood parameters as well as
      performance were measured every week over a period of five weeks. RESULTS: Very
      high training loads of approximately 3.2 hours per day were sustained for 18
      days. Maximum performance (Pmax) and maximum lactate (Lamax) were decreased
      during high-load training phases (overreaching), Pmax, Lamax and endurance
      increased after the tapering period. There were decreases in gonadal and
      hypothalamic steroid hormones (fsh, 1h, prolactin, testosterone) during
      overreaching and increases in these hormones in tapering. Both performance and
      hormonal indices of training load were reflected by deterioration of recovery in
      the Recovery-Stress-Questionnaire for Athletes. CONCLUSIONS: Clear signs of
      overreaching were found after 18 days of intense training of about 3 h.d(-1) in
      these highly-trained athletes, i.e. decreases in performance, gonadal and
      hypothalamic steroid hormones and deterioration of recovery in the psychological
      questionnaire. After tapering values returned to baseline values before the World
      Championship. The findings indicate that overreaching is an integral part of
      successful training regimens and can be analyzed by a multi-factorial approach
      involving biological and psychometric data.

PMID- 11297004
TI  - Acute creatine loading enhances human growth hormone secretion.
AB  - BACKGROUND: The main objective of this study was to explore the effect of acute
      creatine (Cr) ingestion on the secretion of human growth hormone (GH). METHODS:
      In a comparative cross-sectional study, 6 healthy male subjects ingested in
      resting conditions a single dose of 20 g creatine (Cr-test) vs a control (c
      test). During 6 hours the Cr, creatinine and GH concentrations in blood serum
      were measured after Cr ingestion (Cr-test). RESULTS: During the Cr-test, all
      subjects showed a significant stimulation of GH (p<0.05), but with a large
      interindividual variability in the GH response: the difference between Cr-test
      and c-test averaged 83% (SD 45%). For the majority of subjects the maximum GH
      concentration occurred between 2 hrs and 6 hrs after the acute Cr ingestion.
      CONCLUSIONS: In resting conditions and at high dosages Cr enhances GH secretion,
      mimicking the response of strong exercise which also stimulates GH secretion.
      Acute body weight gain and strength increase observed after Cr supplementation
      should consider the indirect anabolic property of Cr.

PMID- 11297005
TI  - Comparison of fructose and glucose ingestion before and during endurance cycling
      to exhaustion.
AB  - BACKGROUND: Pre-exercise and exercise ingestion of fructose and glucose during
      cycling exercise were compared. METHODS:  EXPERIMENTAL DESIGN: Seventeen trained
      subjects ingested a placebo prior to and during a cycling test to exhaustion at
      75% VO2max (control group = CG). One week later, subjects were matched on
      exercise time to exhaustion (ETE) and assigned to a fructose group (FG) or a
      glucose group (GG). Subjects then performed a second cycling test to exhaustion,
      ingesting fructose or glucose doses. For all groups (CG, FG and GG), blood was
      drawn before and at timed intervals during exercise to determine glucose, lactate
      and free fatty acid (FFA) levels. RESULTS: The ETE for CG was less than either FG
      (p<0.02) or GG (p<0.001) but FG and GG were similar. FG and GG did not show any
      differences in blood lactate or blood FFA during the ETE. However, CG FFA levels
      were higher than those of FG (p<0.02) prior to exercise. CONCLUSIONS: This study
      demonstrated that fructose and glucose are of equal value in prolonging ETE in
      endurance cycling Ingesting fructose before and during exercise apparently
      provided a more constant supply of glucose to be available to the working
      muscles. The more stable blood glucose levels with fructose ingestion may be
      beneficial in reducing perceived exhaustion, and thereby allowing for an
      enhancement in exercise performance.

PMID- 11297006
TI  - Nutrition survey in elite rhythmic gymnasts.
AB  - BACKGROUND: Young female rhythmic gymnasts have been identified as a potential
      risk group for malnutrition because of their attitude of weight reduction and
      leanness. METHODS: This study aimed to assess the dietary practices of 20
      rhythmic gymnasts of the Italian national team, on the basis of a three-day food
      records collected by clinical interview. Twenty-four age-matched non-athletic
      females served as controls. RESULTS: The reported energy intake was similar in
      gymnasts and controls (28.5+/-5.6 vs 28.2+/-7.8 kcal/kg b.w., per day), but less
      than the recommended and the estimated requirements. Energy intake from
      carbohydrates was higher (53+/-6 vs 49+/-6%, p<0.05) and that from lipids lower
      (31+/-6 vs 34+/-4%, p<0.05) in gymnasts than in controls. In the former the
      energy supply from breakfast was higher (24+/-2 vs 16+/-4%, p<0.001) and from
      snacks was lower (8+/-9 vs 17+/-10%, p<0.01). Gymnasts also distinguished from
      controls for lower cholesterol and saturated fatty acid intake, and for higher
      fibre (14+/-5 vs 9+/-2 g/1,000 kcal, p<0.001) and Vitamin A dietary content.
      Calcium, iron and zinc intake were less than 100% RDA in both groups.
      CONCLUSIONS: In some ways, dietary practices of rhythmic gymnasts meet
      nutritional recommendations more than those of non athletic controls, though
      discrepancy between reported energy intake and estimated energy requirement
      exists. Suboptimal calcium, iron and zinc intake were observed both in gymnasts
      and in controls, hence minerals supplementation could be required. The dietary
      attitude could be regarded as a positive aspect of rhythmic gymnastics, provided
      athletes, physicians and coaches correct dietary errors and avoid excessive food
      restrictions.

PMID- 11297007
TI  - The application of shock-waves therapy in the treatment of resistant chronic
      painful shoulder. A clinical experience.
AB  - BACKGROUND: To evaluate the efficacy of extracorporeal shockwaves therapy (ESWT)
      in patients with chronic painful shoulder. METHODS:  EXPERIMENTAL DESIGN: a
      prospective design was used with a short term follow-up. SETTING: data were
      collected at the Service of Physioterapy in Villa Stuart Clinic-Rome. PATIENTS:
      72 patients of both sexes with an average age of 38 years (range 18 to 69)
      affected by chronic painful shoulder, whose symptoms lasted more than 6 months.
      INTERVENTIONS: all patients received on average, 2,000 impulses of ESWT at level
      5 energy (0.21 mJ/mm2) according to Dornier Epos equipment one session per week
      for 8 weeks. MEASURES: all cases underwent an instrumental examination with X-ray
      conventional imaging and clinical assessment of pain (visual analogue scale) and
      functional limitation of the shoulder, two weeks before the treatment and at one
      month follow-up. RESULTS: 53% of patient scored excellent results, 14% good, 13%
      fair and 20% poor. In the group of calcifying tendinitis we had a reduction in
      37% and no changes in 63%. CONCLUSIONS: Even with a limited number of cases our
      early results show the efficacy and safety of ESWT in the treatment of chronic
      painful shoulder resistant to other conservative approaches.

PMID- 11297008
TI  - Differences in psychosocial determinants of physical activity in older adults
      participating in organised versus non-organised activities.
AB  - BACKGROUND: With the introduction of the new consensus on 30 minutes of moderate
      physical activity preferably on all days of the week, exercise implemented into
      daily activities is promoted whereas structured activity programs lose
      importance. Activity levels of most older people don't come up with current
      recommendations. Therefore strategies to enhance attendance of older adults in
      physical activities should be developed. Group programs may be more effective in
      changing exercise behaviour of older adults than non-supervised physical
      activity. The purpose of this study was to investigate the differences in level
      of activity and psychosocial determinants of physical activity between seniors
      involved in an exercise class and seniors not engaged in any organised physical
      activity. METHODS: Seventy-five elderly who were currently involved in structured
      exercise classes and 75 elderly who did not participate in any organised physical
      activity during the previous year were recruited in senior citizens' centres and
      were asked to fill out a questionnaire. RESULTS: Subjects involved in an exercise
      program had higher levels of activity and reported more social influences and
      higher self-efficacy compared to the respondents practising on an individual
      basis. No differences were found in perceived barriers or benefits. CONCLUSIONS:
      Exercising in a group program gives the opportunity to accumulate some extra
      physical activity and positively affects the level of activity outside the
      program. Stimulating older adults to join a structured activity program in the
      company of family or friends in order to enhance supporting social influences and
      perceived competence could be an important intervention strategy.

PMID- 11297010
TI  - Maintaining functional capacity: comment on Lemura et al.

PMID- 11297009
TI  - Creatine alpha-ketoglutarate is experimentally unproven.

PMID- 11297011
TI  - Polyamines of the hyperthermophilic archaebacteria belonging to the genera
      Thermococcus and Methanothermus and two new genera Caldivirga and Palaeococcus.
AB  - Cellular polyamines of eight new thermophilic archaebacteria were investigated to
      determine the chemotaxonomic significance of polyamine distribution profiles.
      Hyperthermoacidophilic Caldivirga maquilingensis belonging to the family
      Thermoproteaceae of the Crenarchaeota have a unique polyamine profile comprising
      spermidine, norspermidine and norspermine as the major polyamines. Within the
      order Thermococcales of the Euryarchaeota, the major polyamines of an extremely
      thermophilic terrestrial species of Thermococcus, T. zilligii, were spermidine
      and agmatine, whereas hyperthermophilic submarine species of Thermococcus and
      hyperthermophilic submarine Palaeococcus ferrophilus contained a quaternary
      branched penta-amine, N4-bis(aminopropyl)spermidine, as a major polyamine. A
      hyperthermophilic methanogen, Methanothermus sociabilis, belonging to
      Euryarchaeota, contained spermidine and spermine as the major polyamine.

PMID- 11297012
TI  - Antibiotic susceptibility, serum response and surface properties of Klebsiella
      species.
AB  - Altogether 130 clinical isolates of five Klebsiella species (K. pneumoniae, K.
      planticola, K. oxytoca, K. ornithinolytica and K. terrigena) were characterized,
      for their susceptibility to five antibiotics, for susceptibility to serum
      bactericidal activity and for their hydrophobic properties. All strains exhibited
      ampicillin resistance. Ampicillin/sulbactam, gentamicin and ofloxacin showed
      effectiveness in 63.1, 67.7 and 71.5% of the Klebsiella isolates. K. planticola
      manifested the highest level of resistance to these antibiotics. The majority of
      Klebsiella strains (93.9%) were susceptible to cefuroxime. Sixty-four strains
      (49.2%) were serum resistant and intermediate serum sensitivity was shown by 57
      strains (43.8%). A high percentage of serum resistant strains (65%) was found in
      K. planticola. Moderately hydrophobic properties determined by adherence of
      bacteria to xylene were demonstrated in 25 strains (19.2%).

PMID- 11297013
TI  - Pathogenicity of Vibrio alginolyticus isolated from diseased small abalone
      Haliotis diversicolor supertexta.
AB  - Outbreaks of mass mortality among cultured small abalone Haliotis diversicolor
      supertexta with abscess/ulcers in the mantle occurred in 1998 at Kao-Hsiung,
      Taiwan. A swarming bacterium, strain H-11 was isolated from the haemolymph of the
      moribund small abalone using tryptic soy agar supplemented with 3% NaCl and/or
      thiosulphate citrate bile salt sucrose agar. This strain was characterized and
      identified as Vibrio alginolyticus on the basis of various biochemical tests. The
      H-11 strain and its extracellular products were virulent to small abalones with
      LD50 values of 3.6 x 10(5) colony forming units and 2.96 microg protein/g body
      weight, respectively.

PMID- 11297014
TI  - In vitro antibacterial activity of Chilean red wines against Helicobacter pylori.
AB  - The antibacterial activity of sixteen Chilean red wines (Cabernet Sauvignon,
      Cabernet Merlot, Cabernet Organic and Pinot Noir), and the active extracts of two
      randomly selected wines were assayed for their antibacterial activity on six
      strains of Helicobacter pylori isolated from gastric biopsies. The active
      fraction of the wines was obtained by dichloromethane extraction, and the
      antibacterial activity of the wines and extracts was evaluated by an agar
      diffusion method. All the red wines studied showed some antibacterial activity on
      the six strains of H. pylori, although the strains were heterogeneous in their
      susceptibility to each particular wine. The active fraction of the two wines
      selected also showed good activity against the strains tested. The main active
      compound was identified as resveratrol. The results presented indicate that
      Chilean red wines have antibacterial activity against H. pylori, which depends
      mainly on the presence of resveratrol.

PMID- 11297015
TI  - Luteolin inhibits the growth and arylamine N-acetyl-transferase activity in
      Neisseria gonorrhoeae.
AB  - Growth inhibition and arylamine N-acetyltransferase (NAT) activity in Neisseria
      gonorrhoeae were inhibited by luteolin, a drug which originated from herbs. The
      growth inhibition was based on changes in optical density (OD) using a
      spectrophotometer, and arylamine NAT activity with 2-aminofluorene (2-AF) was
      determined using high pressure liquid chromatography. The inhibition of growth in
      N. gonorrhoeae demonstrated that luteolin elicited a dose-dependent growth
      inhibition in the N. gonorrhoeae cultures. Suspensions of N. gonorrhoeae with or
      without specific concentrations of luteolin cotreatment showed different
      percentages of 2-AF acetylation. The data indicated that there was reduced NAT
      activity associated with increased levels of luteolin in N. gonorrhoeae
      suspensions. Time-course experiments showed that NAT activity measured from
      intact N. gonorrhoeae cells was inhibited by luteolin for at least 4 h. Using
      standard steady-state kinetic analysis, it was demonstrated that luteolin was a
      possible uncompetitive inhibitor to NAT activity in N. gonorrhoeae. This report
      is the first to show that luteolin can inhibit N. gonorrhoeae NAT activity.

PMID- 11297016
TI  - Induction for the expression of yeast metallothionein gene, CUP1, by cobalt.
AB  - Induction for the expression of the metallothionein gene, CUP1, in the yeast
      Saccharomyces cerevisiae by cobalt was examined using a reporter gene with the
      promoter of this gene fused to the coding region of lacZ. The expression of the
      gene was induced by cobalt as well as by copper and silver ions. The activity of
      beta-galactosidase showed high levels after treatment with 1.0 mM cobalt
      chloride. It has been reported that the induction for the transcription of CUP1
      by copper and silver is mediated by the Ace1 transcription factor. However, the
      expression of the gene by cobalt occurred in yeast cells lacking the Ace1 factor.
      These results suggest the presence of a novel cobalt-specific transcription
      factor for the CUP1 gene.

PMID- 11297017
TI  - Facilitation of quadriceps activation following a concentrically controlled knee
      flexion movement: the influence of transition rate.
AB  - STUDY DESIGN: Single group repeated measures design. OBJECTIVE: To determine if
      the rate of transition between knee flexion and extension influences the
      subsequent concentric activation of the quadriceps and knee extension torque
      during reciprocal movements. BACKGROUND: Preloading a muscle by stretching, a
      prior isometric or eccentric muscle action, or a prior movement controlled
      concentrically by the antagonist muscle group increases the maximal torque
      generating capability of the agonist. We hypothesized that the rate of transition
      from the prior movement may be the critical factor that influences the degree of
      muscle facilitation and torque potentiation. Rapid reversal of antagonistic
      movements has been postulated as a potential facilitatory mechanism. METHODS:
      Knee extension torque and electromyographic (EMG) amplitude (dependent variables)
      from 2 of the vasti muscles were recorded while subjects (N = 20; 12 men, 8
      women, mean age, 28.5+/-2.68 years) maximally activated their quadriceps at 3
      constant angular velocities, 100 degrees/s, 200 degrees/s, and 300 degrees/s, and
      2 preload conditions, SLOW and RAPID (independent variables). In the SLOW
      transition condition, subjects actively flexed their knee to 110 degrees from an
      extended position, paused in this position for 3 seconds, and then extended to 0
      degrees. In the RAPID transition condition, the same movement from knee flexion
      to extension was performed without a pause. RESULTS: Peak torque, the root-mean
      square (RMS) average, peak (peak rectified and smoothed), and initial (100
      milliseconds prior to torque onset) EMG amplitudes were all significantly greater
      during the RAPID transition condition. Peak torque decreased with increasing
      movement velocity. There were no interactions between the preload conditions and
      angular velocity on peak torque or the EMG amplitude variables. There was also no
      influence of velocity on the EMG amplitude variables. CONCLUSIONS: The effect of
      preloading the quadriceps by prior concentric activation of the hamstrings is
      dependent on the rate of transition between the flexion and extension movements
      and is due primarily to neural facilitation.

PMID- 11297018
TI  - Determination of functional rotation axes during elevation of the shoulder
      complex.
AB  - STUDY DESIGN: A cross-sectional, descriptive study of shoulder movements
      conducted on nonimpaired subjects. OBJECTIVE: To investigate whether a single
      functional rotation axis about the shoulder complex can be determined during
      elevation in the coronal or sagittal planes, and to identify their location.
      BACKGROUND: Accurate measurement of isokinetic torques about a joint requires
      alignment of the dynamometer axis with an assumed rotation axis of the joint. To
      assess shoulder function on a dynamometer, the location of a single rotation axis
      is not evident because the shoulder joint motion is based on several anatomical
      joints. Therefore, the rotation axis where humerothoracic movements occur should
      be judged as a functional rotation axis. METHODS AND MEASURES: During slow
      elevation movements in the sagittal and coronal plane, the position of the
      epicondyle and acromion were recorded with a motion analysis system. The motion
      trajectory of the elbow coordinates was fitted to a circle and considered an
      estimate of the functional shoulder joint rotation axis in the specified plane.
      RESULTS: The fitted trajectory appeared to be very accurate (root-mean-square
      error < 2%; N = 7). In the sagittal plane, the estimated functional rotation axis
      was found at the humeral head; in the coronal plane, it was located about 13
      centimeters medial relative to the acromion. CONCLUSION: The shoulder complex of
      nonimpaired subjects can act as a hinge joint of the upper arm relative to the
      thorax during elevation in each measured plane.

PMID- 11297019
TI  - Effect of cessation and resumption of static hamstring muscle stretching on joint
      range of motion.
AB  - STUDY DESIGN: Single group repeated measures. OBJECTIVES: To determine the
      effects of cessation and resumption of a hamstring muscle stretching protocol on
      knee range of motion (ROM). BACKGROUND: It is generally accepted that stretching
      exercises result in an increase in ROM. The ability to maintain ROM once
      stretching has ceased and the ability to regain ROM after resumption of the
      stretching exercise is not well-known. METHODS AND MEASURES: Evaluated the effect
      of 6 weeks of static hamstring stretching, 4 weeks with cessation from
      stretching, and 6 weeks with resumption of stretching on knee ROM in 18 inactive
      college students (12 men, 6 women, mean age 21.0 years). The hamstring stretching
      consisted of 2 30-second stretches per day, 5 days per week. Knee ROM was
      measured before and after each of the above phases with an active knee extension
      test. RESULTS: Mean knee ROM increased after the initial stretching period (143+/
      11 to 152+/-9 degrees), decreased to baseline following the cessation period
      (145+/-8 degrees) and again increased following the resumption of stretching but
      was not different from the initial gains (154+/-10 degrees). Unlike the stretch
      limb, the control limb ROM did not change over the 4 measurement times.
      CONCLUSIONS: There was no retention of knee ROM 4 weeks following a 6-week
      stretching protocol and a subsequent stretching period did not enhance the gain
      of knee ROM over the initial stretching period.

PMID- 11297020
TI  - Anthropometric and demographic factors affecting distance hopped and limb
      symmetry index for the crossover hop-for-distance test in high school athletes.
AB  - STUDY DESIGN: Prospective cohort study using a random selection from an
      accessible population. OBJECTIVES: We examined anthropometric and demographic
      characteristics affecting distance hopped (DH) and limb symmetry index (LSI) in
      the crossover hop-for-distance test in uninjured high school athletes.
      BACKGROUND: Between-subject comparisons of hop test results described by DH and
      LSI are common in the literature and clinical practice. The effect that
      anthropometric traits and demographic characteristics have on these measures is
      uncertain but must be known to correctly interpret hop-for-distance test results
      in research or to determine suitability of return to sports. METHODS AND
      MEASURES: For 201 high school athletes (age = 15.15+/-1.45 years, mean weight =
      63.67+/-14.02 kg, mean height = 167.92+/-9.58 cm) completing the crossover hop
      for-distance test, we recorded maximum DH for each leg and calculated the LSI of
      each subject. We performed 2 separate step-wise regression analysis models to
      develop predictive equations for DH and LSI. RESULTS: Age (r = 0.36), weight r =
      0.41), and body fat percentage (r = 0.58) were significant predictors of DH, with
      the regression model explaining 59% of the variability. None of the measured
      variables were significant predictors of LSI (r = 0.03). The regression model
      explained only 3% of the variability of LSI. CONCLUSIONS: The LSI for the
      crossover hop-for-distance test can be compared among all individuals without
      subdividing into groups. Subject characteristics should be as homogeneous as
      possible when comparing DH among subjects or groups.

PMID- 11297021
TI  - Quality of life three months and one year after first treatment for early stage
      breast cancer: influence of treatment and patient characteristics.
AB  - This paper reports the quality of life (QoL) of a large cohort of Australian
      women three and twelve months after surgery for early stage breast cancer (ESBC),
      and shows that the impact of disease and treatment on QoL differed by age,
      education and marital status. Eighty-three percent of eligible patients were
      recruited; 86% had breast conserving surgery and 14% mastectomy. Response rates
      were 93% (n = 305) at three months and 88% (n = 291) at one year. Quality of life
      was measured with the EORTC core questionnaire (QLQ-C30) and an ESBC-specific
      questionnaire. Multilevel analysis was used to estimate the effects and
      interactions of time, treatment and patient characteristics. Most symptoms
      declined between three months and one year, but arm and menopausal symptoms
      persisted. Emotional, social and role functioning improved over time, and fear of
      disease recurrence diminished. Younger women faired worse than older women on a
      broad range of QoL dimensions. Single women and those with less education faired
      worse on a number of dimensions. The negative impact of mastectomy on body image
      was greatest among married women, particularly young married women. These
      sociodemographic distinctions are relevant when discussing treatment options with
      women facing a diagnosis of ESBC.

PMID- 11297022
TI  - Models of health-related quality of life in a population of community-dwelling
      Dutch elderly.
AB  - OBJECTIVE: Though health-related quality of life (HRQoL) is now commonly measured
      as an outcome in clinical trials, the relationships between its components remain
      unclear. The relation of physical symptoms, physical function, and psychological
      symptoms to each other and to overall quality of life is of special interest.
      METHOD: Cross-sectional data from 5,279 community-dwelling elders who
      participated in the Groningen Longitudinal Aging Study were analyzed using
      structural equation modeling techniques. Three models were examined. One "Linear"
      model included: number of chronic medical conditions, physical symptoms, physical
      functioning, activity interference, social function, perceived health and overall
      quality of life in a simple linear progression. Another 'non-linear' model
      included these variables, but allowed effects between non-adjacent variables. A
      third 'non-linear' model included these variables plus anxiety and depressive
      symptoms. RESULTS: The Linear Model did not satisfactorily account for the
      observed data [X2(15df) = 2946.96], so the saturated Non-Linear Model,
      incorporating paths between non-adjacent components, is described. When anxiety
      and depressive symptoms were added to this Non-Linear Model, they fit best in a
      position mediating the relation between perceived health and overall quality of
      life [X2(5df) = 136.78]. CONCLUSIONS: Overall quality of life appears to be
      related to symptom status as directly as it is related to functional status.
      Anxiety and depressive symptoms appear to mediate the relation between general
      health perceptions and overall quality of life. Quality of life measures should
      therefore include assessments of physical and psychological symptom severity as
      well as functional status if they are to truly reflect what matters to patients.
      The disability-adjusted life year (DALY) measure used by the WHO may inadequately
      reflect the effect of symptoms on patient's quality of life.

PMID- 11297023
TI  - The reliability and internal consistency of an Internet-capable computer program
      for measuring utilities.
AB  - OBJECTIVE: The purpose of this study was to assess the reliability and internal
      consistency of measurements of utilities performed with a computer program
      (iMPACT2) designed for Internet surveys and Internet patient decision-support
      systems. METHODS: We implemented the Internet Multimedia Preference Assessor
      Construction Tool, version 2 (iMPACT2) program using the combination of a web
      server, HTML files, and a web-accessible database. The program randomized
      subjects, screened their responses for missing data and failures of internal
      consistency, assisted patients with resolving certain inconsistencies, and, upon
      a subject's completion of the protocol, provided a report of results to the
      research assistant administering the program. To validate the iMPACT2 program, we
      recruited 60 healthy community volunteers and elicited preferences in a research
      lab setting using a visual analog scale (VAS) and the standard gamble (SG) for
      subject's current health and three hypothetical states. For purposes of
      comparison, we also administered a Short Form-12 (SF-12) health-assessment
      questionnaire. Subjects used the computer software on two occasions separated by
      2-4 weeks of time. RESULTS: Visual analog scale and standard gamble ratings for
      subjects' current health were reliable (intraclass correlation coefficient (ICC)
      of 0.82 and 0.84 (two outliers excluded -0.60 without exclusions), respectively)
      were comparable with the reliability of the Physical and Mental Component scales
      of the SF-12 (ICCs of 0.84 and 0.75, respectively). Subjects could easily
      discriminate between hypothetical states (D scores 0.74 for SG and 0.90 for VAS),
      and 94% had a completely internally consistent ordering of preference ratings for
      states. CONCLUSIONS: iMPACT2 produces measurements of standard gamble utilities
      that are reliable and have a high degree of internal consistency. Procedures for
      assessment of utilities developed for desktop computer programs can be translated
      to software designed for the Internet, facilitating the use of utilities and
      endpoints in clinical trials and development of web-based decision-support
      applications for patients. However, further testing, including direct comparisons
      with traditional interviewer administered utility elicitation protocols, is
      needed.

PMID- 11297024
TI  - Patient preferences and utilities for 'off-time' outcomes in the treatment of
      Parkinson's disease.
AB  - The purpose of this study was to derive patient preferences and utilities for
      outcomes associated with treatment of motor fluctuations, or 'off-time', for
      patients with Parkinson's disease (PD). Visual analog scale (VAS) and standard
      gamble (SG) approaches were used with 60 patients to determine patient
      preferences and utilities for 10 health state descriptions. Health state
      descriptions were categorized according to two factors: disease severity, and
      proportion of the day with 'off-time'. There were two representative levels of
      disease severity, based on Hoehn and Yahr stages 1.5 and 2.5: unilateral disease
      with no postural instability, and bilateral disease with some postural
      instability. These severity levels were combined with five levels of 'off-time'
      per day ranging from none to > 75% of the day. Patients' mean preference or
      utility for their own current health ranged from 0.65 +/- 0.20 (VAS) to 0.74 +/-
      0.22 (SG). Patients assigned the lowest mean values to the health state
      description for Hoehn and Yahr stage 2.5 with 'off-time' for > 75% of the day
      (VAS: 0.17 +/- 0.17; SG: 0.49 +/- 0.27). The highest mean values were assigned to
      Hoehn and Yahr stage 1.5 with no 'off-time' (VAS: 0.83 +/- 0.17; SG: 0.85 +/-
      0.18). The results of this study indicated patients with PD would likely seek
      treatment that would minimize the amount of 'off-time' experienced per day, and
      that patients were relatively risk averse.

PMID- 11297025
TI  - Social support and quality of life in patients with coronary artery disease.
AB  - The relationship between perceived social support and domain-specific health
      related quality of life (HRQOL) was examined in a sample of cardiac
      catheterization patients after considering age, gender, race, education, and
      coronary artery disease (CAD) severity. Data was collected on 4,278 cardiac
      catheterization patients (63% males) and included 1,215 patients with non
      significant CAD and 3,063 patients who had significant CAD ( > or = 75% stenosis
      of at least one major coronary artery). Among the patients with significant CAD,
      2,721 were classified as low disease severity and 342 were considered high
      disease severity. Regression models indicated that a lack of social support was
      associated with significantly lower levels of HRQOL across all eight SF-36 HRQOL
      domains after considering disease severity and other demographic factors. The
      models also indicated that social support and other relevant variables interacted
      across various HRQOL domains. Physical function and physical role function were
      lower with age, whereas mental health, emotional role function, and vitality were
      higher with age. Females reported lower HRQOL than males across all domains.
      Minority patients reported lower levels of HRQOL than white patients across four
      domains. Increased disease severity was related to lower levels among four of the
      eight HRQOL domains. The observed interactions of social support with minority
      status, disease severity, and education suggest that a subset of individuals may
      suffer lower levels of HRQOL. These individuals may subsequently require the
      greatest degree of care and potentially benefit most from intervention.

PMID- 11297026
TI  - Men, women and friends--are there differences in relation to mental well-being?
AB  - This is a study on associations between the number of close friends and mental
      well-being in a nationwide sample of the Finnish general population (n = 1,603).
      Mental well-being was assessed by means of the 12-item General Health
      Questionnaire. A total of 3% of the sample had no close friends and another 3%
      had only one. Over half of the sample (52%) reported having five or more friends.
      The overall prevalence of mental distress was 15% in men and 21% in women.
      According to multivariate analyses the risk of mental distress was increased in
      men among those with no friends (odds ratio [OR]: 2.70) and among those who had
      one (OR: 4.32) or two to four friends (OR: 1.75), as compared with those who had
      more friends. In women, having only one friend (OR: 2.30), insufficient family
      support (OR: 1.63) and insufficient support from relatives (OR: 1.77) associated
      with the risk of mental distress. These results suggest that mental well-being
      might be promoted if mentally distressed men seeking professional help were
      supported in building up and maintaining social networks and mentally distressed
      women were supported in harmonizing their family life.

PMID- 11297027
TI  - Measurement of fatigue in cancer patients: further validation of the Fatigue
      Symptom Inventory.
AB  - Fatigue is one of the most common and debilitating symptoms experienced by cancer
      patients, yet until recent years it has received little systematic attention, due
      in part to the lack of adequate instruments to measure fatigue. The primary aim
      of this report is to further validate a recently developed measure of fatigue for
      use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13-item self
      report measure was designed to measure the intensity and duration of fatigue and
      its interference with quality of life. The FSI was originally validated in a
      sample of breast cancer patients and a sample of healthy individuals. In this
      study, the FSI was evaluated in an outpatient sample that included male and
      female cancer patients, as well as some older patients, with a variety of cancer
      diagnoses. A seven-item interference scale was found to have good internal
      consistency, with alpha coefficients above 0.90. Convergent validity was
      demonstrated via comparisons with an existing measure of fatigue. Construct
      validity was demonstrated via comparisons with measure of life satisfaction and
      depression as well as comparisons among subgroups of patients expected to differ
      in their experience of fatigue. Overall, the FSI was further established as a
      valid and reliable measure of fatigue in cancer patients. The potential
      application of this measure in psychosocial oncology research is discussed.

PMID- 11297028
TI  - Evaluating the relationship between pain presentation and health-related quality
      of life in outpatients with metastatic or recurrent neoplastic disease.
AB  - Because cancer pain can in many cases be intermittent, the presence or absence of
      pain in ambulatory care patients on any given clinic visit may not be an accurate
      characterization of the impact of pain on functioning or health-related quality
      of life (HRQOL). The purpose of this study was to describe the relationship
      between temporal aspects of pain presentation and HRQOL among 187 stage III/IV
      cancer patients using the Brief Pain Inventory and the EORTC QLQ-C30. A total of
      43% of patients reported pain the previous week, with 22% reporting no pain at
      the time of assessment. Differences between three pain groups (No Pain, Past
      Pain, and Current Pain) were significant for global HRQOL and five dimensions of
      HRQOL. Severity of pain was also associated with each dimension of HRQOL. This
      study highlights the complex relationship between pain presentation and HRQOL.
      The findings support the continuing need for detailed pain assessments among
      cancer patients treated in ambulatory care settings. Specifically, standardized,
      self-report measures of cancer pain that include 'frequency' as well as severity
      may be the most accurate approach to capture the impact of pain on HRQOL.

PMID- 11297029
TI  - The health-related quality of life of patients with epilepsy compared with angina
      pectoris, rheumatoid arthritis, asthma and chronic obstructive pulmonary disease.
AB  - The objective of this study was to compare the health-related quality of life
      (HRQL) of patients with epilepsy with populations suffering from different
      chronic diseases, using the short form 36 (SF-36) health profile measure. The
      populations to be compared were adult patients drawn from hospital based
      registers, with confirmed epilepsy (n = 397), angina pectoris (n = 785),
      rheumatoid arthritis (n = 1,030), asthma (n = 117) and chronic obstructive
      pulmonary disease (COPD) (n = 221). Health-related quality of life scores were
      compared using analysis of covariance (ANCOVA) for predicting mean scores
      adjusted for age, gender, education and comorbidity. Patients with epilepsy on
      average scored highest on all scales, reflecting that in our sample the majority
      had well-controlled epilepsy. Our results indicate that the HRQL of a
      representative sample of patients with epilepsy is good, when compared with other
      chronic disorders, although reduced in several dimensions compared with a general
      reference population. Patients with rheumatoid arthritis (RA) and COPD scored
      lowest on the physical function scales, while rheumatoid arthritis patients
      reported most pain.

PMID- 11297031
TI  - Comparison of glycocalicin, thrombopoietin and reticulated platelet measurement
      as markers of platelet turnover in HIV+ samples.
AB  - It is important to distinguish between decreased platelet/megakaryocyte
      production or increased peripheral platelet destruction as causes of
      thrombocytopenia. The measurement of reticulated platelets, plasma glycocalicin
      and thrombopoietin (TPO) levels are potentially of use as discriminators.
      Thrombocytopenia occurs in many HIV+ patients, and plasma glycocalicin has
      previously been shown to be elevated in this patient group. Reticulated
      platelets, glycocalicin and TPO were measured in samples from 56 HIV+ subjects
      and 20 healthy normal controls. The glycocalicin index (GCI--the glycocalicin
      levels adjusted for the platelet count) measured in HIV+ subjects was found to be
      significantly elevated when compared to normal controls (mean GCI 1.5 and 1.27, p
      = 0.04), while the percentage of reticulated platelets and TPO levels were not.
      Thrombocytopenic HIV+ subjects had significantly elevated mean GCI (2.8 and 1.4,
      p < 0.0001), TPO (85.2 and 27.2 pg/ml, p = 0.002), percentage of reticulated
      platelets (15.3 and 10.8%, p = 0.01), and significantly reduced absolute numbers
      of reticulated platelets (16.2 and 24.5 x 10(9)/l, p = 0.0004) when compared to
      non-thrombocytopenic HIV+ subjects. GCI and percentage of reticulated platelets
      exhibited a significant positive correlation (r = 0.4, p = 0.002) in HIV+
      subjects. The reticulated platelet, TPO and GCI data suggests that
      thrombocytopenic HIV+ subjects have normal platelet production, and increased
      peripheral platelet destruction.

PMID- 11297030
TI  - A new treatment satisfaction measure for asthmatics: a validation study.
AB  - The Patient Satisfaction with Asthma Medication (PSAM) questionnaire was
      developed because no treatment satisfaction questionnaire could be identified
      that was comprehensive yet brief enough for use in clinical trials. Adult
      moderate asthmatics residing in Canada using an inhaled medication (either
      salmeterol, formoterol, or albuterol) self-administered the questionnaire, which
      also included the Asthma Quality of Life Questionnaire (AQLQ). A total of 53
      asthmatics (70% female, 45% married, mean age: 47 years) completed the
      questionnaire. Using variable clustering, four PSAM scales were identified:
      Inhaler Properties, Comparison with Other Medications, Overall Perception of
      Medication, and Relief. Internal-consistency reliability provided evidence of
      reliability and lack of redundancy (Cronbach's Alpha: 0.82-0.88). Test-retest
      reliability was acceptable (ICC values at or near 0.70). As expected, interscale
      PSAM correlations were moderate to high; correlations between the PSAM and the
      AQLQ were low to moderate. To assess known groups validity, respondents were
      categorized by self-reported degree of asthma control: 'very well controlled',
      'somewhat controlled', and 'not well controlled'. Significant between-groups
      differences were found on all PSAM scales except Inhaler Properties. Patients
      categorized as 'very well controlled' tended to report highest PSAM scale scores.
      The PSAM questionnaire demonstrated reliability and validity in moderate
      asthmatics. Responsiveness should be assessed in future, prospective studies.

PMID- 11297032
TI  - Occurrence of the Asn45Ser mutation in the GPIX gene in a Belgian patient with
      Bernard Soulier syndrome.
AB  - Bernard Soulier Syndrome (BSS) is a rare inherited bleeding disorder caused by a
      defect in the glycoprotein (GP)Ib/IX/V complex. A patient with a bleeding problem
      was diagnosed as having BSS based on the prolonged bleeding time, the absence of
      ristocetin induced platelet aggregations, thrombocytopenia and the presence of
      giant platelets. Analysis of the platelets of the propositus, a 39-year-old
      Belgian female, by flow cytometry revealed a decreased expression of the GPIb/IX
      polypeptides. Western blotting confirmed these results and showed moreover that
      there was a decreased disulfide bridge formation between GPIb alpha and GPIb
      beta. After sequence analysis of the GPIb alpha, GPIb beta and GPIX genes, only a
      mutation in the GPIX gene at position 1826 (A-->G) was identified, changing Asn45
      ->Ser. Restriction analysis with Fnu4H1 demonstrated that the patient was
      homozygous for this mutation. As this Asn45-->Ser mutation in the GPIX gene was
      already found in four unrelated families, i.e. in a British, Austrian, Swedish
      and Finnish one, the occurrence of this mutation in a Belgian patient supports
      the hypothesis of Koskela et al. (1999) that the Asn45Ser mutation in GPIX
      appears to be an ancient mutation shared by northern and central European
      populations. Our present observation of a decreased disulfide bridge formation
      between GPIb alpha and GPIb beta shows that GPIX is not only needed for the
      correct assembly of the complex but might also be needed for the disulfide bridge
      formation between GPIb alpha and GPIb beta.

PMID- 11297033
TI  - Carboxyl terminal sequence of human phospholipase Cgamma2.
AB  - Phospholipase Cgamma2 (PLCgamma2), the predominant isoform of phospholipase C
      expressed in platelets, plays a major role in activation of platelets by
      collagen. Although PLCgamma2 has been shown to be tyrosine phosphorylated upon
      collagen-induced activation, the phosphorylation sites are yet to be determined.
      We have sequenced the 3' terminal cDNA of human phospholipase C-gamma-2 and found
      it different from the human PLCgamma2 cDNA sequence previously reported by Ohta
      et al. (Ohta S, Matsui A, Nazawa Y, Kagawa Y. FEBS Lett 1988; 242: 31-5). There
      is an extra guanosine at position 3723 which causes a shift in the reading frame.
      The new carboxyl terminal amino acid (aa) sequence beyond the frame shift is 88%
      identical to that of rat (21 out of 24 aa residues) which is considerably higher
      than the identity with published sequence (26% identity). The new deduced aa
      sequence contains two tyrosine residues at positions 1245 and 1264 which might be
      phosphorylated upon stimulation and hence might be important for the activation
      of the PLCgamma2.

PMID- 11297034
TI  - Expression of CD61 (beta3 integrin subunit) on canine cells.
AB  - A monoclonal antibody (JM2E5) specific for the integrin beta3 chain, or CD61 or
      GPIIIa subunit, has been employed to determine the expression of the canine
      homologue CD41/CD61 or CD51/CD61 complex on different canine cells in peripheral
      blood lymphocytes, monocytes, granulocytes, platelets, erythrocytes, lymph-node
      cells, spleen cells and breast tumour cells). The canine homologue CD41/CD61 or
      CD51/61 was present on peripheral blood lymphocytes, monocytes, granulocytes,
      breast tumour cells and spleen cells as well as on platelets and it was absent
      from erythrocytes and lymph-node cells. An antigen with components of molecular
      masses of 25/100/120 kDa (under reducing conditions) was immunoprecipitated from
      canine peripheral lymphocytes and platelets, but not from granulocytes or
      monocytes. Expression on canine lymphocytes of the canine homologue of the human
      beta3 integrin chain was unexpected, based on the expression pattern of this
      molecule in human tissue.

PMID- 11297035
TI  - Platelet CD40 ligand (CD40L)--subcellular localization, regulation of expression,
      and inhibition by clopidogrel.
AB  - This study compares the subcellular localization and the regulation of expression
      of the platelet activation markers CD62P and CD63 with CD40 ligand (CD40L) on the
      surface of washed human platelets. CD40L was expressed upon stimulation with a
      wide range of platelet activators. However, quantitative flow cytometry
      demonstrated that, as compared with CD62P and CD63, CD40L expression was low.
      Upon stimulation with thrombin receptor-activating peptide (TRAP-6), all
      activation markers were expressed. In contrast, upon stimulation with low
      concentrations of collagen (1-3 microg/ml), CD40L, but not the granule proteins
      (CD62P, CD63), were expressed. Using immunofluorescence microscopy, a cytoplasmic
      staining was observed for CD40L, and cytoplasmic localization of CD40L was
      verified by Western blotting of subcellular platelet fractions. The staining of
      CD40L was different from that of filamentous actin and only little association of
      CD40L with platelet cytoskeleton was found. Surface expression of CD40L was
      dependent on internal Ca2+ stores and protein kinase C, while the mitogen
      activated protein kinases (ERK, p38) or tyrosine kinases were not involved. ADP
      (30 microM)-induced CD40L expression was not inhibited by aspirin. In contrast,
      clopidogrel treatment completely abolished ADP-induced expression of CD40L.
      Finally, the expression level of CD40L was shown to be upregulated by phorbol
      myristate acetate (PMA) in the promegakaryocytic cell line MEG-01.

PMID- 11297036
TI  - The balance of concurrent aggregation and deaggregation processes in platelets is
      linked to differential occupancy of ADP receptor subtypes.
AB  - Deaggregation, the partial reversal of the initial aggregation of platelets is
      observed following low, but not higher, micromolar ADP concentrations. This study
      tested the hypothesis that deaggregation results from a balance between
      concurrent, opposing, aggregation and deaggregation processes which are ADP
      (adenosine 5'-diphosphate) receptor occupancy-dependent. Aggregation of human
      platelet-rich plasma (PRP) prepared in r-hirudin was assayed in a 96-well plate
      reader over 20 min by measurement of the optical density (OD) at 580 nm.
      Aggregation and the time to reach peak aggregation were directly proportional to
      ADP receptor occupancy. The magnitude and time course of the response to ADP were
      comparable to those previously reported with standard aggregometry. The rate
      constant of platelet deaggregation, as assessed by a four-compartment kinetic
      model, was inversely proportional to agonist concentration. The ratio of the rate
      constants of aggregation and deaggregation was receptor occupancy-dependent and
      directly proportional to aggregation. Consequently, platelet aggregation was
      proportional, and deaggregation inversely proportional, to ADP receptor
      occupancy. We propose that the response of PRP to ADP and to 2-MeS-ADP (2
      methylthioadenosine-diphosphate), in vitro, consists of at least two active,
      concurrent processes, aggregation and deaggregation. Incremental occupancy of the
      P2T ADP receptor subtype attenuates deaggregation and governs the balance between
      these two processes.

PMID- 11297037
TI  - Activation of Gi-coupled receptors releases a tonic state of inhibited platelet
      aggregation.
AB  - Single-receptor pharmacology does not satisfactorily explain the physiology of
      the ADP-induced platelet aggregation response. It has been shown that, in
      addition to Gq-coupled receptor activation, one Gi-coupled receptor, either the
      ADP P2T or the alpha2-adrenoceptor, is required for elicitation of aggregation.
      The underlying mechanism of this action, however, has not been elucidated. By
      systematically assaying the entire time course of the aggregation and its fade
      using two methods of aggregometry, we have investigated the role of graded
      activation of these two Gi-coupled receptors. We demonstrate that constant
      activation of either of two Gq-coupled receptors, the ADP P2Y1 or the 5-HT2A, and
      incremental activation of either of the two Gi-coupled receptors, tightly
      regulates the aggregation response in vitro, through the apparent release of a
      tonic inhibition of platelet aggregation. This tightly regulated release of
      inhibition, which appears analogous to the phenomena of disinhibition observed in
      the central nervous system, may be instrumental for the continuous adaptation of
      the aggregation response to variable physiological conditions.

PMID- 11297038
TI  - Differentiated reactivity of whole blood neonatal platelets to various agonists.
AB  - Neonatal platelets have been occasionally reported to show a reduced response to
      various agonists. The molecular mechanism(s) of such a depressed reactivity
      remains unclear. To further address this problem we studied neonatal platelet
      activation with thrombin, TRAP (thrombin receptor activating peptide, Ser-Phe-Leu
      Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe) and ADP in 42 healthy 1-2 day old
      neonates using a whole peripheral blood flow cytometry. The neonates did not show
      an increased fraction of P-selectin-positive circulating platelets, whereas the
      expression of GPIb (glycoprotein Ib) in resting neonatal platelets was
      significantly lower compared to adults. Neonatal platelets were significantly
      less reactive than adult platelets to thrombin and TRAP, especially at lower
      agonist concentrations, but not to ADP or when incubated for 1 h at room
      temperature. Activation of neonatal platelets with agonists resulted in a marked
      alterations in the expression of P-selectin, whereas the internalization of GPIb
      was not affected. The reduced neonatal platelet sensitivity to thrombin and TRAP
      was accompanied by significantly reduced ATIII (antithrombin III) and increased
      prothrombin fragment F(1+2) in neonatal plasma. We conclude that various receptor
      systems potentially able to bind thrombin are relatively insensitive in neonatal
      platelets. The novelty of our work is that neonatal platelet hyposensitivity is
      not a generalized phenomenon, but concerns only selected agonists and selected
      receptor systems.

PMID- 11297039
TI  - Balancing risks and benefits of deception in assessing genetic screening
      utilization.
AB  - OBJECTIVE: To advocate that research using intentional deception is sometimes
      appropriate. METHODS: A deception paradigm created to assess utilization of
      genetic screening for alcoholism susceptibility is reviewed in the context of
      competing ethical obligations and objections to the procedure. CONCLUSIONS: The
      paradigm is ethically defensible, it generates useful knowledge about future
      utilization of alcoholism screening by college students, and it exposes
      participants to no more than minimal risk. The use of deception to address
      questions related to predictive genetic screening will require investigators to
      balance protection of participants with the need to advance knowledge.

PMID- 11297040
TI  - Risk perception and cigar smoking behavior.
AB  - OBJECTIVE: To examine the cigar smoking perceptions and behaviors of US adults.
      METHODS: A national sample of 1,012 adults was interviewed by telephone. RESULTS:
      Current cigar smokers differed from nonsmokers in perceptions of personal risk
      for cancer and views about cigar smoking as a cancer cause. Both groups showed
      substantial acceptance of the glamorized image of cigarsmokers. CONCLUSION:
      Although recognizing smoking as a cancer cause in general, cigar smokers tended
      to show a self-exempting "optimistic bias" with regard to perceptions of their
      own risks.

PMID- 11297041
TI  - Weight loss behaviors and smoking in college students of diverse ethnicity.
AB  - OBJECTIVE: To evaluate weight concerns, weight-loss practices (including smoking)
      in an ethnically diverse group of university students (58% Hispanic). METHODS:
      Students (n=1,852) completed a survey addressing lifestyle behaviors and weight
      control practices. RESULTS: A greater percentage of females than males practiced
      weight-loss behaviors. More Hispanic and non-Hispanic white students reported
      dieting, exercising, and using weight loss pills to lose weight. Only 4 of the
      females reported their primary reason for smoking was to control their weight.
      CONCLUSION: Gender as well as ethnicity was a dominant factor influencing weight
      loss behaviors/concerns of these young adults.

PMID- 11297042
TI  - Correlates of overweight and weight-loss practices in Missouri.
AB  - OBJECTIVE: To examine potential correlates of overweight and weight-loss
      practices in Missouri. METHODS: Two probability surveys (n=3,010) were used to
      investigate the associations of sociodemographic and health-related factors with
      overweight and attempting, exercising, dieting, and desiring to lose weight.
      RESULTS: Race, gender, and receiving professional advice were strongly associated
      with being overweight. Gender, receiving professional advice, and leisure-time
      physical activity were positively associated with attempting and desiring to lose
      weight. CONCLUSIONS: Public health programs can utilize this knowledge to reduce
      the prevalence of overweight by encouraging professional advice and promoting
      regular exercise.

PMID- 11297043
TI  - A community research partnership to improve the diet of African Americans.
AB  - OBJECTIVE: To describe a community research partnership in which a national
      parent education organization collaborated with academic institutions to develop
      a dietary change program for underserved African American parents. METHODS:
      Qualitative methods were used to characterize issues that impacted partnership
      operations. RESULTS: Data are reported on partnership activities including
      program development and implementation with African American parents. Lessons
      learned and strategies for improving the partnership are presented. CONCLUSIONS:
      Ongoing assessment and evaluation of how a partnership operates, especially in
      the context of multiple sites, are important to sustaining successful
      functioning.

PMID- 11297044
TI  - Predicting regular cigarette use among continuation high school students.
AB  - OBJECTIVE: To provide a 1-year prospective examination of social, behavioral,
      intrapersonal and demographic factors that predict transition from experimental
      to regular cigarette use among continuation high school students. METHODS: A
      cohort of 252 students completed baseline and 1-year follow-up questionnaires on
      health behaviors. RESULTS: Relatively low smoking prevalence estimates, intention
      to smoke in the next year, violence perpetration, perceived stress, sensation
      seeking, and male gender predicted the transition to regular use 1 year later.
      CONCLUSION: Intrapersonal variables may be relatively important in predicting the
      progression from experimental to regular smoking.

PMID- 11297045
TI  - Racial differences in eating disorder attitudes, cigarette, and alcohol use.
AB  - OBJECTIVE: To compare eating disorder attitudes, cigarette, and alcohol use
      between black and white college women. METHOD: Four validated, self-report
      questionnaires were administered. RESULTS: Black women reported significantly
      less substance use. However, substance use, regardless of race, was significantly
      related to eating disorder symptoms, and women at highest risk for an eating
      disorder reported the highest levels of substance use. Also significantly related
      to eating disorder symptoms were negative affect reduction and weight control as
      reasons for substance use. CONCLUSIONS: Black and white women at highest risk for
      an eating disorder also exhibit the greatest potential for substance use.

PMID- 11297046
TI  - Metal exposure during ship repair and shipbreaking procedures.

PMID- 11297048
TI  - Control of nitrous oxide during cryosurgery.

PMID- 11297047
TI  - Mycobacterium tuberculosis risk for elephant handlers and veterinarians.

PMID- 11297049
TI  - Rebuttal to letter of John H Keene concerning our 15(10) 2000 article "resolution
      of sick building syndrome in a high-security facility".

PMID- 11297050
TI  - Surface contamination to UV-curable acrylates in the furniture and parquet
      industry.
AB  - Surface contamination to ultraviolet radiation curable coatings (UV coatings),
      used increasingly in the parquet and furniture industry, is a matter of concern
      as a source for skin contamination. UV coatings contain chemically and
      biologically reactive acrylates, well known as skin contact irritants and
      sensitizers. Surface contamination may spread secondarily to equipment and other
      unexpected areas even outside the workplace. Yet, studies concerning this type of
      contamination are lacking due to lack of suitable sampling methods. Surface
      contamination of the work environment with risk for skin exposure to UV coating
      was measured employing a quantitative adhesive tape sampling method developed for
      this purpose. A pilot study was first performed at three workplaces to evaluate
      the contamination. In the main study, we wanted to locate and identify in detail
      the surface contamination of areas where problems exist, and to determine the
      extent of the problem. Measurements were performed at seven workplaces on two
      separate workdays (round 1 and 2) within a six-month period. Samples were
      collected from the workplaces based on the video monitoring of skin contact
      frequency with the surfaces and categorized into three groups to analyze risk.
      The pilot study indicated that surface contamination to TPGDA containing UV
      coatings was common, found in 76 percent of the surfaces, and varied with a
      maximum of 909 microg TPGDA 10 cm(-2) sampling area. In the main study TPGDA was
      found in 153 out of 196 collected samples (78.1%); for round one 78.1 percent (82
      out of 105 samples) and for round two 78.0 percent (71 out of 91 samples). The
      average TPGDA mass on positive surface samples was on the first round 2,247 +/-
      7,462 microg, and on the second round 2,960 +/- 4,590 microg. We conclude that
      surface contamination to uncured UV coatings at UV-curing lines is common and
      this involves a risk for harmful, unintentional skin exposure to acrylates.

PMID- 11297052
TI  - Allergic respiratory disease and fungal remediation in a building in a
      subtropical climate.
AB  - An outbreak of allergic respiratory disease occurred in a new building that was
      characterized from initial occupancy by the presence of extensive visible mold
      (especially Aspergillus versicolor) on interior surfaces. Epidemiological study
      of the occupants of both the affected building and a comparison neighboring
      structure indicated high rates of respiratory and other symptoms among persons
      working in the affected building. Subsequent clinical evaluations of some persons
      occupying the building for up to five years identified several cases of building
      related allergic respiratory disease, including asthma and hypersensitivity
      pneumonitis. Based on these findings, the building was evacuated before
      remediation began. The mycological goal of the three-year building restoration
      project was to reduce concentration of non-phylloplane fungi such as A.
      versicolor to the lowest feasible level. All visibly colonized materials in the
      building were discarded and all fine dust on interior surfaces was removed by
      vacuuming and/or damp wiping. A medical surveillance program utilizing serial
      self-reported questionnaires and readily available clinical evaluations was
      designed to monitor the health of building occupants after re-entry. Symptom
      rates just prior to building reentry were substantially lower than those found
      before evacuation and have remained unchanged after re-occupancy was completed.
      No new or recrudescent cases of illness are known to have occurred after building
      re-entry.

PMID- 11297051
TI  - Magnetic-field exposures of cable splicers in electrical network distribution
      vaults.
AB  - The purposes of the research reported here were to quantify the power-frequency
      magnetic-field exposures of cable splicers while they were performing tasks in
      energized network distribution vaults and to compare these exposures with
      occupational exposure guideline levels. Network vaults supply electricity to
      commercial and residential urban areas as well as to large buildings.
      Participating workers wore a personal exposure monitor at the waist, kept a
      simple diary to record their work location, and recorded information about the
      vaults and tasks performed. To capture temporal variability, a stationary meter
      was deployed in the vault during a task. Load current in the vault was measured.
      To examine temporal variability over long time periods, stationary meters were
      deployed in selected vaults for one month. Data were collected during 77 tasks in
      69 vaults for 191 person-tasks, representing approximately 400 hours of in-vault
      personal exposure data. Highest exposures were observed in tasks performed near
      secondary conductors. Personal exposure variability arises principally from
      worker movement and activities in the vaults, not from load variability during a
      task. Maximum field during a person-task exceeded the International Committee on
      Non-Ionizing Radiation Protection (ICNIRP) (0.42 millitesla) and the American
      Conference of Governmental Industrial Hygienists (ACGIH) (1.0 millitesla)
      guideline levels during 14 percent and 8 percent of the person-tasks,
      respectively. The mean of measurements during a person-task exceeded those
      guideline levels during 4 percent and 2 percent of the person-tasks,
      respectively. A large number of person-tasks (40%) had measured fields above the
      ACGIH recommended limit of 0.1 millitesla for workers with pacemakers or other
      implanted devices. Based on the frequency and duration of their high exposures,
      cable splicers working in network distribution vaults are one of the most highly
      exposed groups in the electric utility industry. Selective assignment of work
      location and task could minimize the likelihood of exposures for vault workers
      exceeding guideline limits for wearers of pacemakers or other implanted devices.
      Scheduling vault tasks during off-peak hours (nights and weekends) may reduce
      exposures. However, even during these periods exposures in certain vaults can
      still exceed guideline levels.

PMID- 11297053
TI  - Safe use of detergent enzymes in the workplace.
AB  - This article gives a detailed description of a program to control workplace
      exposure to enzymes during manufacture of laundry detergents. We believe this
      same program could, in large part, be re-applied to control exposure to enzymes
      in other industries or to control exposure to other industrial allergens. We
      chose to publish at this time because we believe enzyme use will increase in the
      future. The information contained here could potentially help new users ensure
      safe deployment of enzyme technology. Also, we have recently acquired new
      knowledge to improve our management system: this knowledge could help current
      enzyme users. We offer two new approaches that greatly increase worker
      participation and also improve understanding of the production process. We also
      highlight limitations of traditional air sampling. The new approaches are semi
      quantitative tools to detect, rank, and control sources of dust release and
      product spillage. Our main conclusions are that detergent enzymes can be handled
      safely in the workplace provided there is no visible dust or spillage. Finally,
      we highlight the value of prick testing as a safe, simple tool to objectively
      asses the effectiveness of a hygiene program and to provide an "early alert" in
      the event of outages in the management system.

PMID- 11297054
TI  - Evaluation of organic-vapor respirator cartridge efficiency for hexamethylene
      diisocyanate vapor in the presence of organic solvents.
AB  - Hexamethylene diisocyanate (HDI)-based polyisocyanates are widely used in
      formulating polyurethane coatings. These polyisocyanates contain a small amount
      of HDI monomer and the American Conference of Governmental Industrial Hygienists
      (ACGIH) recommends an eight-hour time-weighted average (TWA) threshold limit
      value (TLV) of 5 ppb for HDI. Some polyurethane (PU) paint applicators have used
      air-purifying paint spray respirators with organic vapor cartridges and
      particulate pre-filters. In this study, the effect of typical paint solvents on
      the efficiency of organic vapor cartridges (OVC) for HDI vapor was tested. A
      Teflon-coated polycarbonate exposure chamber was constructed. Three OVCs were
      simultaneously tested in an atmosphere containing HDI vapor and solvents. The
      test atmosphere was generated by evaporating a mixture of paint solvents
      containing n-butyl acetate, propylene glycol mono methyl ether acetate, toluene
      and methyl ethyl ketone, and neat HDI. The target challenge concentrations were
      20 times the TLV for HDI and 10 times the combined TLV for the solvent mixture.
      The test atmosphere, with 20 or 80 percent relative humidity and at room
      temperature, was drawn through each cartridge at 32 L/min for 40 hours. However,
      in the last 8 hours of the test, the atmosphere had only HDI vapor. The pre- and
      the post-cartridge atmospheres were periodically sampled for HDI and the
      solvents. The study concluded that under the test conditions there was no
      detectable breakthrough of HDI from the OVCs. The average calculated efficiency
      of the OVCs, based on the HDI analytical limit of quantitation, was >99.4 percent
      for the 40 hours tested. The overall average challenge concentration of HDI was
      105 ppb and the average combined solvent concentration was 3,176 mg/m3. The
      cartridges were saturated with solvents within the first 10 hours of testing;
      nevertheless, continued challenging with HDI vapor and solvents did not show any
      HDI breakthrough. Solvent breakthrough and breathing resistance, rather than HDI
      breakthrough, would be the key parameters in life expectancy calculations for
      cartridge change out schedules.

PMID- 11297055
TI  - Beryllium sensitization and chronic beryllium disease at a former nuclear weapons
      facility.
AB  - The prevalence of beryllium sensitization and chronic beryllium disease by job
      category was examined among individuals tested in the Rocky Flats Beryllium
      Health Surveillance Program. The program offered ongoing beryllium health
      surveillance for any current or former employee who believed they may have been
      exposed to beryllium at the Rocky Flats Environmental Technology Site. Of the
      18,589 living individuals contacted, 7,573 requested participation and 6,614
      (87.3%) eventually participated. Of this group, 78.2 percent were found to have
      verifiable job and building histories. The beryllium lymphocyte proliferation
      test was used to identify beryllium-sensitized individuals. Sensitization and
      chronic beryllium disease rates were analyzed with respect to gender, building
      work location(s), and length of employment at Rocky Flats. Several job categories
      and buildings were strongly associated with the 81 cases of chronic beryllium
      disease and the additional 154 cases of beryllium sensitization in this
      population. Beryllium sensitization was highest among beryllium machinists, 11.4
      percent (odds ratio = 3.04, compared to the remainder of those tested, 95 %
      confidence interval = 1.48, 3.97) and health physics technicians, 11.9 percent
      (odds ratio = 2.87, 95% confidence interval = 1.12, 7.36). However, odds ratios
      were also increased among custodial employees, 5.64 percent (odds ratio = 1.30,
      95% confidence interval = 0.92, 1.85) and other job titles that were thought to
      have only minimal potential for exposure to beryllium.

PMID- 11297056
TI  - Gastrointestinal anastomosis with histoacryl glue in rats.
AB  - Technical difficulties in creating gastrointestinal anastomosis in infants and
      young children, because of the small lumen, are well known and may be complicated
      by a narrow passage, anastomotic obstruction, gastric stasis, recurrent vomiting,
      and failure to gain weight. The search for alternative easier technique was the
      basis for this study. The primary aim was to evaluate the safety of anastomosis
      between the stomach and a loop of the jejunum performed by using the tissue
      adhesive Histoacryl glue in comparison with the same anastomosis performed
      conventionally with absorbable sutures. We compared the results of gastrojejunal
      anastomosis in rats using either Histoacryl (n-butyl cyanoacrylate) glue or
      continuous, absorbable sutures. Sixty-four Sprague-Dawley rats were divided into
      4 groups of 16 rats each. Gastroenterostomy was performed with either type of
      anastomosis with and without truncal vagotomy. The criteria ofgastroenterostomy
      investigated included anastomotic leakage, stricture formation, adhesion
      formation, and histological examination. The pH of gastric secretion was measured
      with intact gastric innervation and after vagotmy in all rats. The time to
      complete each type of anastomosis was measured in minutes. Anastomotic stricture,
      leak, peritonitis, and death happened in three rats in each group with intact
      vagal innervation, in two rats after vagotomy and anastomosis with Histoacryl,
      and in one rat after vagotomy and anastomosis with sutures. The results showed no
      statistically significant differences between the various groups, except the
      shorter time for performing the glued anastomosis (5-7 min) compared to the
      conventional anastomosis (16-21 min). In conclusion, gastroenterostomy with
      Histoacryl in rats appears to be as safe as conventional suture anastomosis,
      saves operating time, and is not affected by gastric acidity.

PMID- 11297057
TI  - A primate model for discordant pig to primate kidney xenotransplantation without
      hyperacute graft rejection.
AB  - Organs transplanted between phylogenetically disparate species, such as from the
      pig into the primate, are subject to intragraft deposition of preformed recipient
      immunoglobulin M (IgM) antibodies with subsequent complement activation finally
      leading to complete and rapid destruction of the xenograft (hyperacute graft
      rejection, HAR). Current therapeutic strategies for abrogation of HAR include
      pretransplant antibody absorption by specific or nonspecific extracorporeal
      column perfusion, ex vivo donor organ perfusion, the administration of substances
      interfering with complement activation, or even the genetic alteration of the
      donor. Here, in the pig to cynomolgus monkey species combination, we are
      describing an experimental model for abrogation of HAR by using large, relative
      to the recipient weight, oversized donor kidneys as xenotransplants. Porcine
      kidney xenotransplantation (n = 15) was performed using large white pigs of
      different weights and ages as organ donors and cynomolgus monkeys as recipients.
      In grafts with an organ weight below 50 g (20 to 48 g, median 25 g), primary
      nonfunction (PNF) of the porcine kidney was observed in 11 out of 12 cases and
      complete HAR in 5 out of 12 experiments. In contrast, none of three grafts with a
      donor organ weight >70 g showed signs of HAR or PNF. In one animal, a second
      porcine kidney from the same donor (23 g) was successfully transplanted
      immediately after HAR and subsequent removal of a first porcine kidney (20 g). By
      using appropriate immunohistochemistry stainings of reperfusion biopsies,
      profound deposition of recipient natural antibodies in both small and large
      xenografts was shown, with only scarce deposition of C3 and C5b-9 in the latter,
      indicating only incomplete intragraft activation of the complement cascade in
      these organs. Intraoperative cardiac output (CO) measurements performed in 7
      experiments demonstrated a 20 to 50% decrease in CO following reperfusion in 6
      out of 7 grafts irrespective of the donor organ weight. The intraoperative
      decrease in CO was not associated with perioperative morbidity or mortality. The
      use of oversized doner kidneys can enable the study of a variety of immunologic
      and physiologic sequela beyond HAR associated with life-supporting discordant
      primate kidney transplantation.

PMID- 11297058
TI  - Ancient Indian civilization: ahead by a nose.

PMID- 11297059
TI  - Important role for endothelins in acute hepatic ischemia/reperfusion injury.
AB  - The aim of this study was to explore the complex role of endothelins (ETs) in
      hepatic ischemia-reperfusion injury and to minimize this type of injury by
      nonselective ET receptor blockade. In an in vivo rat model, hepatic ischemia was
      induced for 30 min. The rats were divided into three groups: (1) sham operated,
      (2) untreated ischemic, and (3) group treated with the nonselective ET receptor
      antagonist bosentan (1 mg/kg body weight iv). Blockage of the ET system during
      ischemia-reperfusion was assessed by: (1) in vivo microscopic analysis, (2)
      measurement of local tissue PO2, (3) laser Doppler flowmetry, (4) transaminases,
      and (5) tumor necrosis factor (TNF)- serum levels. During liver ischemia, anoxia
      (mean liver pO2 decreased from 14.7 to 1.5 mm Hg) and TNF- (levels rose from 0
      pg/mL to 145.3 pg/mL at the end ofischemia) were associated with the release of
      ETs. Immunoreactive ET-1 (ir-ET-1) plasma levels (basal levels: 12.1+/-1.8 pg/mL)
      went up by 2.6-fold (32.1+/-6.8 pg/mL) after 15 min and by 11.7-fold (142.1+/
      32.6 pg/mL) after 120 min of reperfusion. Increased plasma levels of ir-ET-1 were
      associated with sinusoidal constriction to 77.6+/-7.1% of basal diameters. This
      constriction led to significant decreases in perfusion rate (77+/-3%), local
      tissue PO2 (6.9+/-2.7 mm Hg), and erythrocyte flux (61.7+/-13.8% of basal
      values). Hepatocellular damage, evaluated via the serum level of aspartate
      aminotransferase (AST, increase to 393.5+/-68.3 U/L, preoperative 23.9+/-2.0 U/L)
      was detectable 6 h after reperfusion (p < .05). Administration of bosentan before
      30 min of ischemia significantly reduced ischemia-reperfusion injury and was
      associated with an increase of ir-ET-1 levels to 110.8+/-12.0 pg/mL and 94.1+/
      25.0 pg/mL after 15 and 120 min of reperfusion. Sinusoidal diameters were
      maintained at nearly 100% in the treatment group instead of 77%, while perfusion
      rate (88+/-2%) and tissue PO2 (12.1+/-1.0 mm Hg) rose significantly in contrast
      with the nontreatment group (p < .05). Hepatocellular damage was reduced (AST
      levels after 6 h of reperfusion 244.0+/-34.4 U/L, p <.05), and leukocyte sticking
      and rolling were diminished (p < .01). In the treatment group, bosentan values of
      5.6+/-0.7 and 2.9+/-0.4 ng/mL after 15 and 120 min of reperfusion were measured.
      In conclusion the release of endothelins is combined with microcirculatory
      disturbances and local hypoxia, thereby causing liver damage. By protecting the
      liver microcirculation, ET receptor blockade of both receptors at a low dose
      increased blood and oxygen supply to the liver and reduced hepatocellular injury.
      These results constitute the bases for further studies and transfer into clinical
      practice.

PMID- 11297060
TI  - Collagen I/III and matrix metalloproteinases (MMP) 1 and 13 in the fascia of
      patients with incisional hernias.
AB  - The late appearance ofincisional hernias several years after laparotomy and the
      high recurrence rates after operation strongly imply the presence of a disorder
      of the connective tissue, although a specific defect in patients with incisional
      hernias has not yet been identified. In the present study we used both
      immunohistochemistry and Western blot analysis to evaluate the ratio of collagen
      I and III and the expression of the metalloproteinases (MMP) 1 and 13 in the
      fascia of patients with incisional or recurrent incisional hernias. Samples of
      healthy skin or stable skin scar in patients without hernias served as controls.
      Altogether, our data indicated a significantly decreased ratio of collagen I/III
      in the fascia of patients with incisional hernias and recurrent incisional
      hernias. Furthermore, in these patients the expression of MMP-1 was decreased
      compared to the controls, whereas MMP-13 could not be detected in any fascia
      sample, with or without hernias present. For the first time, our results give
      evidence of the existence of a possible collagen disorder in these patients. The
      decreased ratio ofcollagen I/III is explainable due to a relative increase of
      collagen type III, which is known to be characterized by thin fibril diameters
      and lowered mechanical strength. The altered collagen ratio might be the result
      of the decreased activity of MMP-1, whereas the absent MMP-13 expression did not
      seem to modify the scar formation. Thus, our data indicate the presence of
      collagen metabolic disorders in patients with incisional hernias and recurrent
      incisional hernias. Furthermore, these results might explain the poor results of
      a mesh-free hernia repair, which again builds up scar tissue of inadequate
      collagen composition and strength.

PMID- 11297061
TI  - A novel technique in a sheep model for evaluating prosthetic heart valve
      performance.
AB  - There have been many various animal studies to evaluate the structural integrity
      and antithrombogenicity of prosthetic heart valves. We were interested in
      developing a novel sheep model to study the thrombogenicity of mechanical heart
      valves placed into the systemic circulation but without the need for cardiac
      bypass. Also, we wanted to minimize the risk ofparaplegia from complete thoracic
      aortic clamping. Six sheep underwent left lateral thoracotomy for placement of a
      mechanical heart valve in parallel with the descending thoracic aorta. A valved
      conduit with a dacron tube graft sutured to the back end was fashioned. Employing
      partial aortic occlusion with a side-biting clamp, the proximal and distal ends
      were anastomosed in an end-to-side fashion. Once flow was confirmed through the
      graft, the native aorta was occulded with umbilical tape. The sheep received no
      postoperative anticoagulation. The median operative time and estimated blood loss
      (EBL) was 170 min and 250 cc, respectively. Patency of the valved conduits was
      confirmed during the initial procedure, and there was no incidence of paraplegia
      postoperatively. Two animals expired shortly after extubation and at necropsy the
      valved conduits were patent with preserved valve function. The four survivors
      were sacrificed a median of 37 days postoperatively. Prior to euthanasia, the
      valved conduits were evaluated in situ with ultrasound. In all cases, the valves
      had clot formation at the hinges, which prevented active movement of the
      leaflets. This novel in vivo technique provides an alternative in testing the
      thrombogenicity of prosthetic heart valves without cardiac bypass or the risk of
      paraplegia in an animal that is extremely sensitive to complete aortic cross
      clamp.

PMID- 11297062
TI  - L-selectin blockade and liver function in rats after uncontrolled hemorrhagic
      shock.
AB  - Hemorrhagic shock (HS) and resuscitation can be seen as a global body ischemia
      reperfusion (I/R) injury characterized by neutrophil infiltration and organ
      damage. Liver dysfunction occurs early after HS. Adhesion molecules are needed
      for the first steps ofneutrophil migration. Thus, the purpose of this study was
      to investigate the role of L-selectin in the liver after uncontrolled HS and
      resuscitation. Forty-eight Sprague Dawley rats were subjected to uncontrolled HS
      and resuscitation. Animals were divided into three groups: sham, uncontrolled HS
      and resuscitation, and uncontrolled HS and resuscitation with anti-L-selectin
      treatment. At 6 we evaluated liver injury tests, liver tissue myeloperoxidase
      (MPO), and liver histology. Survival was followed for 3 days and compared between
      groups. Statistical analysis included Fisher's exact test and one-way analysis of
      variance. Survival significantly increased from 30% in the control group to 60%
      in the treated group (p < .05). Hepatocellular and structural injury as well as
      neutrophil infiltration was significantly decreased in treated animals (p < .05).
      Thus, blockade of L-selectin resulted in decreased hepatocellular injury and
      increased survival in our model of uncontrolled HS. Selectins may be important
      therapeutic targets for blockade in the treatment of HS.

PMID- 11297063
TI  - Can maturation arrest occur at the stage of spermiogenesis?
AB  - This article attempts to clarify the pathological condition during which the
      maturation of the germinal epithelium is unable to evolve beyond a certain stage
      and is characterized as maturation arrest. Emphasis is given to the histological
      entity named spermiogenic arrest.

PMID- 11297064
TI  - Expression of HSP70-2 gene during germ cell apoptosis in rat unilateral
      cryptorchid testes.
AB  - To investigate the role of Hsp70-2 gene in germ cell apoptosis induced by heat
      stress, its expression changes were examined in rat normal and unilateral
      cryptorchid testes by using in situ hybridization, immunohistochemistry, and
      northern blot analysis techniques. The results showed that the expression level
      of Hsp70-2 gene declined slightly at the early stage of germ cell apoptosis, and
      dropped dramatically when most of the germ cells were undergoing apoptosis on day
      7.5 after the induction of cryptorchidism. This report suggests for the first
      time that Hsp70-2 gene might not inhibit the apoptosis of germ cells at the early
      stage in cryptorchid testes. Hsp70-2 gene does not belong to the immediate early
      related genes that are responsible for germ cell apoptosis induced by heat
      stress.

PMID- 11297065
TI  - Adrenal steroids in human prostatic cancer cell lines.
AB  - Adrenal androgens function as an androgen source within prostate and androgen
      target tissue. This study compares the ability of three human prostatic cancer
      cell lines to metabolize the adrenal androgens, dehydroepiandrosterone (DHEA),
      and androstenedione under living culture conditions. Androgen-independent cell
      lines PC-3 and DU145 and androgen-dependent cell line LNCaP were investigated.
      The effect of glucuronide and sulfate conjugates was also investigated. There was
      a strong tendency in PC-3 or DU145 to convert androstenedione to DHEA or DHEA-S
      reservoir. On the other hand, LNCaP was capable of converting DHEA into
      androstenedione and subsequently into dihydrotestosterone (DHT). Moreover,
      androgens were converted into a glucuronide conjugate in LNCaP, but not in PC-3
      or DU145. As a result, the metabolism of the adrenal precursor shifted to
      androgen formation in LNCaP. This could be confirmed by means of reverse
      transcription-PCR of uridine diphosphoglucuronosyl-transferase (UGT) 2B15.
      Kinetic properties of UGT activity in LNCaP revealed DHT to be a better substrate
      than testosterone. In conclusion, the findings show that the adrenal precursor
      pool has the potential to contribute to the regulation of prostatic cells.
      Moreover, the presence of UGT activities in LNCaP may have a regulatory effect on
      the active androgen level in the intracellular environment.

PMID- 11297066
TI  - Creatine kinase isoforms in the seminal plasma and the purified human sperm.
AB  - In previous conventional reports sperm and seminal plasma were not well separated
      and therefore it was highly probable that isoform (CK-BB) of seminal plasma was
      determined together with that of sperm. The authors developed a method to purify
      sperm specimen free from seminal plasma. Human sperm was purified by means of the
      continuous-step density gradient centrifugation with an inner column and the
      subsequent modified swim-up procedure. CK isoforms in the purified sperm and the
      seminal plasma were analyzed by ion exchange chromatography and electrophoresis.
      The purified sperm contained mitochondrial CK-MiMi as well as cytosolic CK, of
      which isoform was almost occupied by CK-MM but CK-BB was not detected. On the
      other hand, CK isoform in the seminal plasma was detected as CK-BB alone. CK
      activity in human sperm and seminal plasma were 2.0 +/- 0.7 x 10(-6) IU/10(6)
      sperm and 661 +/- 360 IU/L, respectively. CK activity in the seminal plasma gave
      no correlation with the semen parameters.

PMID- 11297067
TI  - Substance P and beta-endorphin act as possible chemoattractants of mouse sperm.
AB  - The effect of beta-endorphin and substance P on mouse sperm motion was examined
      in an in vitro model. The number of mouse sperm cells migrating to mediuin
      containing substance P in pharmacological concentrations of 5, 25, and 50 ng/mL
      were significantly higher than the number migrating to control. This effect was
      observed after 3 h at a concentration of 5 ng/mL and 1 h at 25 and 50 ng/mL.
      Demonstrated changes in spermatozoa behavior in the presence of substance P were
      time and concentration dependent. These effects were interpreted as chemotaxis
      but not chemokinesis of sperm induced by influence of this tachykinin on membrane
      receptors. The presence of beta-endorphin in incubation fluid in concentrations
      of 5, 25, and 50 ng/mL did not cause any visible changes or decrease sperm
      migration. Substance P contained in follicular fluid played a direct and
      important role in the process of mammalian fertilization.

PMID- 11297068
TI  - Pregnancy rates in relation to time intervals between repeat sperm-retrieval
      procedures.
AB  - A total of 76 repeat sperm retrievals were carried out in 47 azoospermic men. The
      outcome of the procedures was evaluated regarding to the interval between two
      successive procedures. Sperm motility and pregnancy rate were not increased by
      increasing the interval between two successive sperm retrievals from less than 90
      days to more than 180 days. The pregnancy rate declined from 50% with a less than
      90-day interval to 25% with a more than 180-day interval. The trend did not quite
      reach the significance level. Pregnancy was obtained in only 27% of the couples
      where TESE was done the last time against 48 and 57% where PESA and TESA,
      respectively, were performed the last time (p < .05). This study suggests that
      sperm retrieval procedures in men with obstructive azoospermia can be carried out
      with time intervals of only 3 months to obtain an optimal pregnancy rate, and it
      might suggest that an epididymal aspiration procedure should be preferred for a
      TESE.

PMID- 11297069
TI  - Effect of dietary plant and animal protein intake on sperm quality in monkeys.
AB  - This study was conducted to evaluate the influence of animal and plant protein
      diets on sperm quality indices over 120 days, using the vervet monkey
      (Cercopithecus aethiops), as a model. These experiments were divided into a 60
      day period of high-protein consumption (+/-17% crude protein), followed by a 60
      day term of sustainable protein intake (+/-9% crude protein). All the diets were
      designed to be similar, except for the source of dietary protein that the animals
      consumed. High-protein diets containing milk solids or maize + legumes had no
      significant effect on sperm quality parameters over the first 60 days. During the
      next 60 days of the investigation, sustainable plant and animal protein diets had
      differential effects on a number of sperm quality indices. When compared to the
      plant-based diet, the monkeys that were given the animal protein diet containing
      milk solids had lower sperm counts (p < .04), reduced sperm motility (p = .04),
      higher sperm midpiece abnormalities (p < .05), and a trend (p = .10) towards
      increased sperm head defects. These findings shed some light on the impact of
      variable dietary proteins on sperm quality, but should be followed by longer-term
      investigations around this important reproductive health issue.

PMID- 11297070
TI  - Sperm characteristics and accessory sex gland functions in HIV-infected men.
AB  - A comparative study was carried out in the andrology clinic, Parirenyatwa
      Hospital, Harare, Zimbabwe, to investigate the sperm characteristics and
      accessory sex gland functions in HIV-infected individuals. Sixty-two patients
      with infertility problems who attended the clinic were requested to donate semen
      and blood after consent was obtained. HIV antibodies in paired semen and blood
      samples, sperm morphology, sperm count, sperm motility, seminal leucocytes,
      seminal fructose, seminal neutral alpha-glucosidase, and citric acid were
      analyzed. Nine out of 31 blood samples tested positive, while 21 out of 62 semen
      samples were positive for HIV. Leucocytospermia was associated with HIV
      seropositive men (p < .01). The accessory sex gland function, as evaluated by
      biochemical markers, was not affected in HIV-seropositive men. HIV causes
      impairment of sperm motility by activating seminal leucocytes, which in turn
      induce oxidative stress on the sperm. Leucocytospermia is almost always present
      in HIV-seropositive men.

PMID- 11297071
TI  - Reproductive parameters of male dromedary and bactrian camels.
AB  - Functional anatomy of male reproductive organs and reproductive physiology of
      dromedary and bactrian camels are quite similar except for some differences in
      the seasonal pattern of reproductive events: left testes bigger than right;
      scrotum not pendulous; vas deferens very convoluted with 2 mm diameter; prostate
      divided into 2 parts by septum, with many ducts; bulbourethral (Cowper's) glands
      well developed and seminal vesicle absent; fibroelastic penis has "prescrotal"
      sigmoid flexure and the glans resembles crochet needle; triangular-shaped prepuce
      directed posteriorly to open to the rear, and can move cranially or caudally
      during erection or urination, respectively; semen ejaculate, 1-12 mL in volume
      with little gelatinous material, coagulates and liquifies within minutes; total
      sperm/ejaculate 6 x 10(9) sperm/mL; semen contains PGE1, PGE(2x,LH), estradiol
      progesterone/other metabolites; semen collected by AV used for bulls with long
      copulation time; ovulation induced 36-48 h after mating or insemination; sperm of
      a short life of 1-6 h at 0.4 degrees C, is prolonged in presence of
      mucopolysaccharide gel; fresh semen inseminated. Topics of future research on
      endocrinology of reproduction, gonadal physiology, semen biology assisted
      reproductive technology, and gene transfer to germ cells of camels are outlined.
      The prevention and control of STD is an important component of camel stud
      management to improve reproductive performance in this species.

PMID- 11297072
TI  - Predictive value of sperm chromatin condensation (aniline blue staining) in the
      assessment of male fertility.
AB  - A case control study was carried out to determine the value of sperm chromatin
      condensation in the assessment of male fertility. A total of 165 semen samples
      from 90 patients (cases) and 75 healthy donors (control) were examined for
      chromatin condensation (aniline blue staining), as well as conventional sperm
      parameters, notably sperm morphology, sperm count, and progressive motility.
      Whereas only 55 +/- 12.0% of the samples from the infertile patients were
      unstained by aniline blue (chromatin condensed), 78 +/- 19.0% of the samples in
      the control group did not take up the stain (chromatin condensed). A significant
      difference (p < .001) was observed between the two groups. Similarly, the
      difference between the mean percentage of morphologically normal spermatozoa for
      the infertile patients (12.1 +/- 1.2%) and the control (23.9 +/- 1.9%) was very
      significant (p < .001). In addition, only 50 out of the 90 patients (55.5%) had a
      normal sperm count, whereas all the 75 (100%) were normal in the control group.
      By comparing between the two groups a significant difference (p < .001) was also
      observed. Furthermore, a significant difference (p < .001) was also found between
      the cases and the control with regard to the percentage of spermatozoa
      illustrating linear progressive motility (40 +/- 9.7% vs. 70 +/- 12.3%). However,
      no correlation was found between sperm chromatin condensation and morphology,
      count, and motility. This study suggests that chromatin condensation constitutes
      a valuable parameter in the assessment of male fertility, completely independent
      of conventional sperm parameters. Consequently, the inclusion of chromatin
      condensation to routine laboratory investigations of semen prior to assisted
      reproduction is strongly recommended.

PMID- 11297073
TI  - Unenhanced helical CT in the evaluation of the urinary tract in children and
      young adults following urinary tract reconstruction: comparison with sonography.
AB  - PURPOSE: To compare the accuracy of unenhanced, helical CT with sonography for
      the detection of complications of urinary tract reconstruction. MATERIALS AND
      METHODS: Forty-six kidneys in 24 patients were examined with CT and sonography.
      All scans were assessed for ease of renal visualization, presence of renal,
      ureteral, and bladder calculi, renal scars, hydronephrosis, and abdominal wall
      hernia. The results of both imaging modalities were independently reported.
      RESULTS: CT provided excellent visualization of all 46 kidneys, while sonography
      provided poor visualization of 8 kidneys (17%) (P < 0.001). CT detected calculi
      in 10 kidneys, 1 ureter, and 7 bladders. Sonography detected calculi in only 2
      kidneys, and 2 bladders. Overall, CT detected significantly more calculi than US
      (18 vs 4, P = 0.01). CT detected scarring in 15 kidneys, while sonography
      detected scarring in 10. Hydronephrosis was detected in 6 kidneys by CT and in 8
      kidneys by sonography. Three abdominal wall hernias were seen at CT that were not
      seen at sonography. CONCLUSION: CT is superior to sonography for the detection of
      urinary tract calculi and renal scarring. CT will demonstrate abdominal wall
      hernias that are unsuspected.

PMID- 11297074
TI  - Renal venous thrombosis with calcification and preservation of renal function.
AB  - Two neonates were found on US to have branching linear calcification in the renal
      parenchyma, right sided in one and bilateral in the other. CT confirmed the
      presence of branching calcification in the kidneys and demonstrated calcified
      thrombus in the inferior vena cava in both babies. Antenatal detection of adrenal
      haemorrhage in one baby and presence of calcification at the age of 3 days in the
      other indicate that thrombosis probably occurred before birth. The kidneys
      remained normal in size, and uptake of 99mTc-labelled dimercaptosuccinic acid
      (99mTc-DMSA) was normal on follow-up examination. The presence of branching
      calcification and normal renal size probably indicates good prognosis for renal
      function in neonates in whom renal venous thrombosis is found and may indicate
      prenatal thrombosis.

PMID- 11297075
TI  - Accuracy of percutaneous lung biopsy for invasive pulmonary aspergillosis.
AB  - BACKGROUND: Invasive pulmonary aspergillosis is fulminant and often fatal in
      immunosuppressed patients. Percutaneous biopsy may select patients who could
      benefit from surgical resection. OBJECTIVE: We sought to determine the accuracy
      of percutaneous biopsy for pediatric invasive pulmonary aspergillosis. MATERIALS
      AND METHODS: We retrospectively reviewed 28 imaging-guided percutaneous biopsies
      of the lungs of 24 children with suspected pulmonary aspergillosis. Twenty-two
      were being treated for malignancy and two for congenital immunodeficiency; 15 had
      received bone-marrow transplants. The accuracy of the percutaneous lung biopsy
      was determined by subsequent surgical resection, autopsy, or clinical course.
      RESULTS: Histopathological studies showed ten biopsy specimens with septate
      hyphae, indicating a mold, and seven with Aspergillus flavus colonies in culture.
      The remaining 18 biopsies revealed no fungi. No patient had progressive
      aspergillosis after negative biopsy. Invasive pulmonary mold was detected by
      percutaneous biopsy with 100% (10/10) sensitivity and 100% (18/18) specificity.
      Percutaneous biopsy results influenced the surgical decision in 86% (24 of 28) of
      the cases. Bleeding complicated the biopsy in 46% (13/28) and hastened one death.
      CONCLUSION: Percutaneous biopsy of the lung is an accurate technique for the
      diagnosis of invasive pulmonary aspergillosis and correctly determines which
      immunosuppressed pediatric patients would benefit from therapeutic pulmonary
      resection.

PMID- 11297076
TI  - Cisterna magna clot and subsequent post-hemorrhagic hydrocephalus.
AB  - BACKGROUND: Posthemorrhagic hydrocephalus (PHH) is an ominous complication of
      intraventricular hemorrhage (IVH) in premature infants. Previous studies have
      correlated lateral intraventricular clot with subsequent PHH, but there are no
      studies assessing the outcome of clot in the cisterna magna (CM). OBJECTIVE: The
      purpose of this study was to determine if the identification of clot in the CM on
      the initial positive cranial ultrasound for intraventricular hemorrhage increased
      the risk of subsequent PHH. MATERIALS AND METHODS: A review of ultrasound records
      over a 4-year period identified 41 neonates with at least grade 2 IVH who had
      specific CM views prospectively performed. RESULTS: Thirty-six survived more than
      3 months. Overall, 22 (61%) developed hydrocephalus. On the initial positive
      cranial ultrasound, CM blood was identified in 21 (58%). Of these 18 (86%)
      developed hydrocephalus [odds ratio (OR) 16.5, confidence interval (CI) 2.5
      125.7, P < 0.001] and 14 (67%) required intervention or remained dilated (OR
      28.0, CI 2.8-1265.8). All patients that required permanent shunt placement had
      initial CM clot (P < 0.01). Initial ventriculomegaly was not a significant
      predictor of subsequent hydrocephalus, but a dilated third ventricle (> or = 8
      mm) was (OR 9.0, CI 1.2-103.3, P < 0.04). Asymmetric intraventricular clot
      filling of more than 50% was not predictive of hydrocephalus, but symmetric clot
      of more than 50% was (OR 10.8, CI 1.4-61.6, P < 0.01). Nine neonates had
      concomitant parenchymal damage with varying outcomes (three shunted, two
      persistent ventriculomegaly, four resolved with normal sized ventricles).
      CONCLUSION: In this study CM clot significantly increased the risk and was a
      better predictor of posthemorrhagic hydrocephalus than initial hydrocephalus.

PMID- 11297077
TI  - Prenatal MR findings in a case of aneurysm of the vein of Galen.
AB  - We describe a case of aneurysm of the vein of Galen (AVG), which was diagnosed by
      intrauterine US, MRI and MRA. The baby girl was born at 35 weeks' gestation. She
      had severe clinical symptoms at birth and died at 29 h of age from intractable
      congestive heart failure. Intrauterine US detected an intracranial aneurysm and
      cardiomegaly due to excessive arteriovenous shunting. Intrauterine MRI (SSFSE)
      confirmed the diagnosis of AVG, and intrauterine MRA (2D-TOF) successfully
      demonstrated the anatomical structure of the AVG. MRA may be a useful additional
      sequence to evaluate AVG, and 2D-TOF is thought to be an appropriate technique
      for scanning fetal AVG.

PMID- 11297078
TI  - MR diagnosis of cerebellar infarction due to vertebral artery dissection in
      children.
AB  - Posterior circulation infarction is uncommon in children. We describe the
      clinical presentation and radiological findings in two children with cerebellar
      infarction resulting from dissection of the vertebral artery. We emphasize that
      vertebral artery injury should be considered in a child with acute symptoms and
      signs of ischaemia in the posterior circulation. MRI and MRA may be helpful in
      the diagnosis of cerebellar infarction and vertebral artery abnormality.

PMID- 11297079
TI  - Wernicke's encephalopathy in a child: case report and MR findings.
AB  - We report a child affected by Wernicke's encephalopathy (WE), which was
      unsuspected clinically. MRI suggested the correct diagnosis and prompted
      appropriate thiamine replacement. WE is a difficult condition to recognise,
      especially in children, and MRI may be useful in the diagnosis of the disease.

PMID- 11297080
TI  - Somatostatin receptor scintigraphy in the management of cerebral malignant
      ectomesenchymoma: a case report.
AB  - A 10-year-old girl presented with a cerebral malignant ectomesenchymoma (MEM), a
      very unusual tumour with undifferentiated mesenchymal as well as ectodermal
      elements. Somatostatin receptor scintigraphy (SRS) was performed during the
      diagnostic workup. The recurrent residual tumour mass was exactly visualized with
      SRS, and was negative after successful treatment of the patient. The potential
      application of SRS in initial staging, follow-up and therapy planning in MEM is
      discussed. This is the first application of SRS in MEM.

PMID- 11297081
TI  - Imaging findings of perforative appendicitis: a pictorial review.
AB  - Appendicitis is common in children. Early diagnosis depends on recognition of
      characteristic signs and symptoms: right lower quadrant or periumbilical pain,
      localized tenderness, fever, and leukocytosis. Because these classic features may
      be difficult to elicit or masked by other complaints, the incidence of
      perforative appendicitis in children is high. This paper reviews the imaging
      sequelae with emphasis on CT and sonography findings. Areas of focus include
      abdominopelvic abscess, peritonitis, pyelephlebitis, pyelethrombosis, and hepatic
      abscess. Secondary involvement of the urinary and gastrointestinal tracts is also
      discussed.

PMID- 11297082
TI  - Appendiceal and appendiceal-ileocolic intussusception: sonographic and
      radiographic evaluation.
AB  - The sonographic appearances of two children with appendiceal intussusception and
      two others with appendiceal-intestinal intussusception are described. All the
      cases were documented by barium enema and surgically confirmed.

PMID- 11297083
TI  - Hypovolemic shock after air reduction of intussusception.
AB  - A 7-month-old white baby girl developed hypovolemic shock requiring resuscitation
      secondary to an air enema reduction of intussusception. The implications of this
      case for standardization of the management techniques in this setting are
      emphasized.

PMID- 11297084
TI  - Intrapancreatic duodenal duplication cyst with inversion of the superior
      mesenteric vessels: CT findings.
AB  - We present a case of intrapancreatic duodenal duplication cyst and inversion of
      the superior mesenteric vessels. CT findings of this association are discussed.

PMID- 11297085
TI  - Short-term follow-up of the juvenile rheumatoid knee with fat-saturated 3D MRI.
AB  - OBJECTIVE: To determine the correlation between clinical status and 3D, fat
      saturated contrast-enhanced MRI findings in assessing the response to treatment
      in patients with knee-joint involvement from juvenile rheumatoid arthritis (JRA).
      MATERIALS AND METHODS: Synovial hypertrophy, effusion, cartilage and epiphyseal
      status were scored using spin-echo (SE) T1-weighted, SE T2-weighted and contrast
      enhanced, fat-suppressed 3D MRI in 42 knees of 21 patients. MRI findings were
      evaluated by scoring results and compared with the clinical scoring results.
      Progression, improvement and equivalence were analysed between 0-3 and 3-6
      months, both clinically and by MRI. RESULTS: Fat-suppression imaging generated
      high contrast between cartilage, synovium, effusion and bone. Correlation
      coefficients according to progression, improvement and equivalent findings of
      months 1-3 and months 3-6 comparison of clinical and MRI scores were found to be
      0.50 and 0.70, respectively. CONCLUSION: Contrast-enhanced 3D MRI with fat
      suppression provides good discrimination between synovial hypertrophy and fluid.
      Fat-suppressed imaging offers better contrast between cartilage and synovium.
      Long-term MRI follow-up of JRA improves direct follow-up of pathological changes
      and helps in modifying treatment regimens.

PMID- 11297086
TI  - Alveolar soft-part sarcoma: a rare soft-tissue malignancy with distinctive
      clinical and radiological features.
AB  - Alveolar soft-part sarcoma (ASPS) is a rare tumour. Certain distinctive clinical
      and radiological features suggest the correct diagnosis. There is moderate
      predilection for young women. ASPS almost always arises in skeletal muscle and
      occurs most frequently in the lower limbs. There is often a long clinical history
      and a large mass at presentation. Two young females with ASPS presented with very
      vascular tumours in the thigh, with prominent intra- and extra-tumoural blood
      vessels. The imaging findings and the existing literature are reviewed.

PMID- 11297087
TI  - Isolated sternal fracture--a swing-related injury in two children.
AB  - Isolated fracture of the sternum is an uncommon injury in a child. We report two
      cases of sternal fracture following falls from swings, which illustrate the
      mechanisms of injury in sternal fracture. One fracture resulted from a flexion
      compression injury of the thoracic spine, which has very rarely been reported in
      children. Sternal fracture should be considered in the differential diagnosis of
      acute chest pain in a child where there has been an activity involving
      hyperflexion force.

PMID- 11297088
TI  - Diagnosis of hypochondroplasia: the role of radiological interpretation. Italian
      Study Group for Hypochondroplasia.
AB  - BACKGROUND: Hypochondroplasia is characterised by phenotypic and genetic
      heterogeneity. Differentiation from other conditions with disproportionate short
      stature is often difficult. OBJECTIVE: To determine the reliability of
      radiological interpretation in the diagnosis of hypochondroplasia and to evaluate
      the most typical skeletal abnormalities. These data were correlated with
      molecular findings. MATERIALS AND METHODS: We enrolled 21 patients with suspected
      hypochondroplasia based on the radiological criteria most often reported in the
      literature on this disease. Height, sitting height and head circumference were
      measured in all patients. Radiographs of the lumbar spine, left leg, pelvis and
      left hand were obtained. The presence of the N540K mutation in the fibroblast
      growth factor receptor 3 (FGFR3) gene was verified by restriction enzyme
      digestion. All radiographs which enabled the selection of patients were reviewed
      a second time by two paediatric radiologists in a blinded examination. Their
      results were compared. RESULTS: Both radiologists confirmed the diagnosis in 10
      out of 21 patients, while in the other 52% of cases they excluded the disease,
      were uncertain or they did not agree on the final interpretation of the data. The
      best agreement rate was obtained in the evaluation of the lumbar spine and the
      legs. The radiological features of the nine patients (43%) carrying the N540K
      substitution were not remarkably different from the ones reported in the patients
      without this mutation. CONCLUSION: Our study shows that the crucial skeletal
      regions on which to focus the diagnosis of hypochondroplasia are the lumbar spine
      and legs, while the pelvis and hands seem to be less characteristic. To reduce
      the risk of misdiagnosis, accurate radiological and clinical evaluation is
      needed, especially in cases without a defined genetic defect.

PMID- 11297089
TI  - Usefulness of MRI for differentiating the different varieties of duplicated
      uterus.

PMID- 11297091
TI  - Help! Unusual X-ray appearances of a congenital bone disease of unknown
      aetiology.

PMID- 11297090
TI  - Clinical aspects of pectus deformities.

PMID- 11297092
TI  - Progressive vascular calcification in autoimmune polyglandular syndrome type I.

PMID- 11297093
TI  - Impact of irrigation on malaria in Africa: paddies paradox.
AB  - The high population growth rate of the African continent has led to an increased
      demand for food and is in danger of outstripping agricultural production. In
      order to meet this need, many governments have sought ways of improving food
      production by initiating large-scale irrigation projects, involving reclamation
      of arid and semi-arid areas for the cultivation of crops. Although crop
      irrigation promises one solution to alleviating hunger and encourages economic
      growth, irrigation has often been blamed for aggravating disease in local
      communities. Malaria is one of the major tropical diseases associated with
      irrigation schemes, and changes in the transmission pattern of this disease
      following irrigation development have been a perennial subject of debate. It has
      often been assumed that high numbers of malaria vector Anopheles mosquitoes
      (Diptera: Culicidae) resulting from irrigation schemes lead inevitably to
      increased malaria in local communities. However, recent studies in Africa have
      revealed a more complex picture. Increased numbers of vectors following
      irrigation can lead to increased malaria in areas of unstable transmission, where
      people have little or no immunity to malaria parasites, such as the African
      highlands and desert fringes. But for most of sub-Saharan Africa, where malaria
      is stable, the introduction of crop irrigation has little impact on malaria
      transmission. Indeed, there is growing evidence that for many sites there is less
      malaria in irrigated communities than surrounding areas. The explanation for this
      finding is still unresolved but, in some cases at least, can be attributed to
      displacement of the most endophilic and anthropophilic malaria vector Anopheles
      funestus Giles by An. arabiensis Patton with lower vectorial capacity, as the
      latter thrives more than the former in ricefields. Similarly, among members of
      the An. gambiae complex, some cytotypes of An. gambiae sensu stricto are more
      vectorial than others. For example, the Mopti form has high vectorial capacity
      and breeds perennially in irrigated sites, whereas the savanna form is often
      sympatric but more seasonal. Also we suggest that many communities near
      irrigation schemes benefit from the greater wealth created by these schemes.
      Consequently irrigation communities often have greater use of bednets, better
      access to improved healthcare and receive fewer infective bites compared with
      those outside such development schemes. Thus, in most cases, irrigation schemes
      in Africa do not appear to increase malaria risk, except in areas of unstable
      transmission. However, developers should take the opportunity to improve health
      care facilities for local communities when planning irrigation schemes wherever
      they occur.

PMID- 11297095
TI  - Temephos-resistant larvae of Simulium sanctipauli associated with a distinctive
      new chromosome inversion in untreated rivers of south-western Ghana.
AB  - Larvae of the Simulium damnosum Theobald complex (Diptera: Simuliidae) were
      sampled in June 1996 from two sites in south-west Ghana where larviciding has not
      been applied: Sutri Rapids on the Tano river (05 degrees 23 minutes N 02 degrees
      38 minures W) and Sekyere-Heman on the Pra river (05 degrees 11 minutes N 01
      degrees 35 minutes W). All specimens were identified as Simulium sanctipauli
      Vajime & Dunbar sensu stricto (Diptera: Simuliidae). Bioassays with temephos
      (organophosphorus larvicide employed by the Onchocerciasis Programme for
      systematic treatment of most rivers across West Africa since the 1970s) showed
      about five-fold resistance in the Tano population (LC95 2.37-3.14 mg/L) and
      slight tolerance to temephos in the Pra population (LC95 0.67-0.76 mg/L), vs. the
      diagnostic concentration of 0.625 mg/L. Larval salivary polytene chromosomes of
      S. sanctipauli showed fixed inversions 1S-24/24, standard IIL-6 and a new
      inversion IL/36 polymorphism at Sutri on the Tano. These karyotype
      characteristics differ from those of temephos-resistant S. sanctipauli in rivers
      of C te d'Ivoire and other sites on the Tano in Ghana. Thus, temephos resistance
      in S. sanctipauli at Sutri is associated with distinct chromosomal
      configurations, showing that immigration was unlikely. This resistance could have
      been locally selected by exposure of S. sanctipauli larval populations to
      agrochemicals run-off from cocoa, coffee and oil plantations flanking the rivers.

PMID- 11297094
TI  - Combined pyrethroid and carbamate 'two-in-one' treated mosquito nets: field
      efficacy against pyrethroid-resistant Anopheles gambiae and Culex
      quinquefasciatus.
AB  - A new approach is proposed in the treatment of mosquito nets, using a 'two-in
      one' combination of pyrethroid and non-pyrethroid insecticides applied to
      different parts of bednets. The objectives are mainly to overcome certain
      limitations of pyrethroid-impregnated bednets currently recommended for malaria
      control purposes. Apart from developing alternatives to pyrethroid dependency, we
      sought to counteract pyrethroid irritant effects on mosquitoes (excito
      repellency) and resistance to pyrethroids. The idea takes advantage of the
      presumed host-seeking behaviour of mosquitoes confronted by a net draped over a
      bed, whereby the mosquito may explore the net from the top downwards. Thus, nets
      could be more effective if treated on the upper part with residual non-irritant
      insecticide (carbamate or organophosphate) and with a pyrethroid on the lower
      part. Sequential exposure to different insecticides with distinct modes of action
      is equivalent to the use of a mixture as a potential method of managing
      insecticide resistance. We also intended to improve the control of nuisance
      mosquitoes, especially Culex quinquefasciatus Say (Diptera: Culicidae) that often
      survive pyrethroids, in order to encourage public compliance with use of
      insecticide-treated nets (ITNs). Polyester bednets were pretreated with residual
      pyrethroid (bifenthrin 50 mg/m2 or deltamethrin 25 mg/m2) on the lower half and
      with carbamate (carbosulfan 300 mg/m2) on the upper half to minimize contact with
      net users. Unreplicated examples of these 'two-in-one' treated nets were field
      tested against wild mosquitoes, in comparison with an untreated net and bednets
      treated with each insecticide alone, including PermaNet wash-resistant
      formulation of deltamethrin 50 mg/m2. Overnight tests involved volunteers
      sleeping under the experimental bednets in verandah-trap huts at Yaokofikro, near
      Bouake in C te d'Ivoire, where the main malaria vector Anopheles gambiae Giles,
      as well as Culex quinquefasciatus Say, are highly resistant to pyrethroids.
      Efficacy of these ITNs was assessed in the huts by four entomological criteria:
      deterrency and induced exophily (effects on hut entry and exit), blood-feeding
      and mortality rates (immediate and delayed). Overall, the best impact was
      achieved by the bednet treated with carbosulfan alone, followed by 'two-in-one'
      treatments with carbosulfan plus pyrethroid. Blood-feeding rates were 13% An.
      gambiae and 17% Cx. quinquefasciatus in huts with untreated nets, but only 3%
      with carbosulfan ITNs, 7-11% with combined ITN treatment, 6-8% An. gambiae and 12
      14% Cx. quinquefasciatus with pyrethroid alone. Mosquitoes that entered the huts
      were killed sooner by nets with combined treatment than by pyrethroid alone.
      Mortality-rates in response to ITNs with carbosulfan (alone or combined with
      pyrethroid) were significantly greater for Cx. quinquefasciatus, but not for An.
      gambiae, compared to ITNs with only pyrethroid. About 20% of sleepers reported
      potential side-effects (headache and/or sneezing) from use of ITN treated with
      carbosulfan alone. Further development of this new 'two-in-one' ITN concept
      requires a range of investigations (choice of effective products, cost-benefit
      analysis, safety, etc.) leading to factory production of wash-resistant
      insecticidal nets treated with complementary insecticides.

PMID- 11297096
TI  - Larvicidal activity of endectocides against pest flies in the dung of treated
      cattle.
AB  - Cattle were treated with topical formulations of endectocides to assess the
      larvicidal activity of faecal residues against horn fly, Haematobia irritans
      (L.), house fly, Musca domestica L., and stable fly, Stomoxys calcitrans (L.)
      (Diptera: Muscidae). In laboratory bioassays, doramectin, eprinomectin and
      ivermectin suppressed horn fly in dung of cattle treated at least 4 weeks
      previously and suppressed house fly and stable fly in dung of cattle treated 1-5
      weeks previously. Moxidectin suppressed horn fly in dung from cattle treated no
      more than one week previously and did not suppress house fly and stable fly.
      Results combined for the three species across two experiments suggested that,
      ranked in descending order of larvicidal activity, doramectin > ivermectin
      approximately = eprinomectin >> moxidectin.

PMID- 11297097
TI  - Rhesus monkey model for Leishmania major transmitted by Phlebotomus papatasi
      sandfly bites.
AB  - Leishmaniasis research needs a near-human model for investigations of natural
      infection processes, immunological responses and evaluation of treatments.
      Therefore, we developed a reproducible system using Leishmania major Yakimoff &
      Schokhor (Trypanosomatidae: Kinetoplastida), the cause of Old World zoonotic
      cutaneous leishmaniasis (ZCL), transmitted to rhesus monkeys Macaca mulatta
      (Zimmerman) (Primates: Cercopithecidae) by sandfly bites of experimentally
      infected Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae). Eight monkeys of
      presumed Indian origin (Leishmania naive) were exposed to bites of female
      sandflies that had been infected with L. major by membrane-feeding on human blood
      seeded with amastigotes isolated from hamster footpad lesions. Infection rates of
      membrane-fed sandflies averaged > 85% seven days after the infective feed, with
      uniformly high numbers of promastigotes in the stomodaeal valve region of the
      sandfly gut. Nodules and ulcerating dermal lesions developed on 7/8 monkeys 2-4
      weeks post-bite and persisted for 3-7 months. Monkeys also developed satellite
      lesions beyond the area of sandfly bites on the head, but not on the chest. Three
      re-challenged monkeys developed lesions that healed faster than lesions from
      their primary challenges. After infection, monkeys developed delayed type
      hypersensitivity (DTH) responses to a panel of Leishmania skin test antigens
      (LSTA) and, when tested by ELISA and IFA, showed significant post-infection
      antibody titres which typically rose for approximately 170 days and then
      gradually receded during the next 100 days following the first challenge. After
      the second challenge, antibody titres spiked higher within approximately 50 days
      and receded more rapidly. In contrast, four rhesus macaques of Chinese origin
      developed no lesions following infected sandfly bites, although they raised
      antibodies and LSTA reactions, indicating subclinical infection.

PMID- 11297098
TI  - Experimental skin lesions from larvae of the bot fly Dermatobia hominis.
AB  - Skin biopsies from larvae of Rattus norvegicus, experimentally infested with
      Dermatobia hominis (Linnaeus Jr) (Diptera: Cuterebridae), were processed for
      histopathological studies. Two days after infestation, the first-stage larvae
      (L1) were located deep in the dermis, surrounded by an inflamed area infiltrated
      predominantly by neutrophils. On the fourth day a thin necrotic layer could be
      seen close to the larvae, surrounded by large numbers of neutrophils,
      lymphocytes, macrophages with a few eosinophils and mast cells. A small warble
      was formed after the fourth day, increasing in size until the seventh day, when
      the L1 moulted to the second-stage larva (L2). The inflammatory process continued
      with increasing numbers of neutrophils, macrophages, lymphocytes, eosinophils and
      mast cells invading the area, as well as the proliferation of fibroblasts and
      endothelial cells and the appearance of a few localized haemorrhages. After 18-20
      days, the L2 moulted to the third-stage larva (L3), when a few plasma cells could
      be seen in the inflamed area. At 25-30 days there was a reduction in the necrotic
      layer, as well as in the number of neutrophils and lymphocytes, although large
      amounts of eosinophils, plasma cells, and collagen fibres were seen. The L3
      usually left the host after 30 days. Two days later, the larval cavity was
      reduced, mast cells infiltrated the region and collagen fibre production were
      increased. After 7 days, an intense infiltration of plasma cells and scattered
      necrotic areas could be seen. A scar formed after 10 days. This study showed the
      laboratory rat to be a suitable model for studies of D. hominis infestation.

PMID- 11297099
TI  - Biting behaviour and potential vector status of anthropophilic blackflies in a
      new focus of human onchocerciasis at Minacu, central Brazil.
AB  - Monthly collections were made of man-biting female blackflies: Simulium
      auripellitum Enderlein, S. guianense Wise, S. minusculum Lutz and S. nigrimanum
      Macquart (Diptera: Simuliidae) from four catching stations in the newly
      discovered focus of human onchocerciasis at Minacu (13 degrees 35 minutes S 48
      degrees 18 minutes W), 300 km north of Brasilia in Goias State. These provided
      baseline data on biting habits, population density and seasonal prevalence during
      the year before completion of the Serra da Mesa hydroelectric dam on the Rio
      Tocantins near Minacu, in a project investigating the effect of dam construction
      on onchocerciasis transmission in the area. All four simuliid species were most
      abundant during the dry season, and only bit in low numbers (S. auripellitum S.
      minusculum, S. nigrimanum) or were absent (S. guianense) in the wet season.
      Simulium minusculum was the predominant species at all catching stations, being
      particularly abundant by the large River Tocantins. The other three species were
      mainly associated with smaller rivers. In the dry season, biting rhythms of S.
      minusculum varied with catching site, while S. nigrimanum showed peaks of
      activity in early morning and during the afternoon. Experimental infection with
      Onchocerca volvulus (Leuckart) (Nematoda: Onchocercidae), from a human volunteer,
      showed that this parasite could develop fully in the four simuliid species, which
      are all considered to be potential vectors in the area.

PMID- 11297100
TI  - Risk factors in habitats of the tick Ixodes ricinus influencing human exposure to
      Ehrlichia phagocytophila bacteria.
AB  - Ixodes ricinus L. (Acari: Ixodida) were sampled during 1996-99 in southern
      Scotland, on vegetation using cloth drags, on humans by removal from clothing and
      on roe deer (Capreolus capreolus L.) by searching legs of culled deer.
      Developmental microclimate was recorded by automatic recorders and questing
      microclimate by portable instruments during tick collections. Ticks and deer were
      examined for infection with Ehrlichia phagocytophila bacteria (Rickettsiales)
      using microscopy and polymerase chain reaction. This pathogen causes tick-borne
      fever of sheep in Europe and human granulocytic ehrlichiosis in North America,
      but in Europe human clinical ehrlichiosis due to E. phagocytophila has not been
      recorded despite serological evidence of exposure. Among three types of habitat,
      coniferous woodland was most infested with questing ticks (560 ticks/km of drag;
      mean numbers collected on long trousers: 24.3 larvae, 13.5 nymphs and 0.8 adult
      ticks/km walked), deciduous woodland had slightly lower infestation (426 ticks/km
      drag) and upland sheep pasture had much lower infestation (220 ticks/km drag). Of
      the three main vegetation types, bracken was least infested (360 ticks/km drag),
      ericas most (430 ticks/km drag) and grassland had intermediate infestation
      density (413 ticks/km drag). Questing and developmental microclimates were poor
      predictors of exposure within these habitats, except lower infestation of
      pastures was attributed to greater illumination there. Collectors who walked a
      total of 300 km through all habitats (taking 360 h in all seasons), wearing
      cotton trousers hanging outside rubber boots, were bitten by only four nymphs and
      11 larvae of I. ricinus (but no adult ticks). There was a negative correlation
      between densities of deer and ticks collected, although presence of deer remains
      a major indicator of exposure. The proportion of infected ticks was fairly
      uniform at four sites studied. Overall prevalence of E. phagocytophila in I.
      ricinus was 3.3% in nymphs (40/1203) but only approximately 1.5% in adults of
      both sexes (although males do not bite). It was estimated that nymphs of I.
      ricinus gave 4.4% probability of one infected bite/person/year (for occupational
      exposure during this research) due to presence in all seasons and habitats, their
      human biting rate of 0.011 nymphs/h or 0.013 nymphs/km and widespread infection
      with E. phagocytophila. The frequency distribution of intensity of infection in
      ticks was approximately normal (mean 98 morulae/nymph infected), thus there is a
      high risk of receiving a high dose from any one infected tick bite.

PMID- 11297101
TI  - Zoophily of Anopheles arabiensis and An. gambiae in Madagascar demonstrated by
      odour-baited entry traps.
AB  - In Madagascar we used odour-baited entry traps (OBETs) for host choice tests of
      wild female anopheline mosquitoes (Diptera: Culicidae) at representative
      localities on the East and West sides of the island (villages Fenoarivo and
      Tsararano, respectively) and at the southern margin of the central plateau
      (Zazafotsy village, 800 m altitude). No insecticide house-spraying operations
      have been undertaken at these villages. Odours from a man and a calf of similar
      mass, concealed in different tents, were drawn by fans into separate OBETs set
      side by side. Traps were alternated to compensate for position effects, and
      different pairs of individual baits were employed for successive replicates.
      Totals of 266 An. funestus Giles sensu stricto and 362 An. gambiae Giles sensu
      lato were collected in 48 trap nights during March-June 1999. For each mosquito
      species the 'index of anthropophily' was defined as the proportion of females
      caught in the human-baited trap. For An. funestus this index was found to be
      consistently greater than 0.5 (value for random choice between traps/hosts),
      indicating that this species 'preferred' human to calf odour (index=0.83).
      Conversely, the index of anthropophily for An. gambiae s.l. indicated they
      'chose' calf in preference to human odour (index=0.26). No significant
      differences of relative preference for calf or man were detected between
      villages; geographical variance accounted for <8% of the total experimental
      variance. Molecular identifications of 181 specimens of the An. gambiae complex
      (approximately 50% of the samples) revealed only An. arabiensis Patton at
      Tsararano and Zazafotsy, but >97% An. gambiae Giles sensu stricto at Fenoarivo,
      in accordance with prior knowledge of the differential distributions of these
      sibling species on the island. Predominant zoophily (i.e. intrinsic 'preference'
      for cattle odours) by both An. arabiensis and An. gambiae s.s. in Madagascar
      contrasts with their greater anthropophily in continental Africa.

PMID- 11297102
TI  - Quantification of pyrethroid insecticides from treated bednets using a mosquito
      recombinant glutathione S-transferase.
AB  - Recombinant glutathione S-transferase (agGST1-6) from the malaria vector mosquito
      Anopheles gambiae Giles (Diptera: Culicidae) was expressed in Escherichia coli
      using a pET3a vector system. The expressed enzyme was biochemically active with
      reduced glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Activity of
      agGST1-6 with GSH and CDNB was inhibited to different degrees by both alpha-cyano
      and non-alpha-cyano pyrethroid insecticides. This inhibition was used to develop
      an assay for quantification of pyrethroids. Standard curves of insecticide
      concentration against percentage of enzyme inhibition or volume of iodine
      solution were established by spectrophotometry and iodine volumetric titration,
      respectively, for permethrin and deltamethrin. These assays allowed estimation of
      pyrethroid concentrations both spectrophotometrically and visually. For the
      residue assay of each insecticide, a cut-off point of 50% of the initial
      pyrethroid impregnation concentration was used, which should differentiate
      between biologically active and inactive treated bednets. The cross-reactivity of
      the primary permethrin photodegradants (3-phenoxyalcohol and 3-phenoxybenzoic
      acid) with the recombinant agGST1-6 was assayed in the same system. No agGST1-6
      inhibition by the insecticide metabolites was observed, suggesting that the
      system is unaffected by primary permethrin metabolites and will accurately
      measure insecticide parent compound concentrations. The estimated pyrethroid
      insecticide concentrations, given spectrophotometrically and by iodine titration
      assay, were comparable to those obtained by direct HPLC quantification of
      residues extracted from bednets. Hence, it should be relatively easy to adapt
      this method to produce a test kit for residue quantification in the field.

PMID- 11297103
TI  - Susceptibility of mosquitoes in central Taiwan to natural infections of
      Dirofilaria immitis.
AB  - From October 1997 to September 1998, 3085 Culex quinquefasciatus (Say) (Diptera:
      Culicidae), 584 Cx. tritaeniorhynchus (Giles) (Diptera: Culicidae), 392 Cx.
      annulus (Theobald) (Diptera: Culicidae), 374 Aedes albopictus (Skuse) (Diptera:
      Culicidae) and 102 Armigeres subalbatus (Coquillet) (Diptera: Culicidae) were
      collected and examined for Dirofilaria immitis (Leidy) (Spirurida: Filariidae)
      infection. However, only Cx. quinquefasciatus and Ae. albopictus were infected,
      with a prevalence of 4.28% and 3.74%, respectively. The intensity of D. immitis
      found in Ae. albopictus (3.43 larvae/mosquito) was higher than that found in Cx.
      quinquefasciatus (2.89 larvae/mosquito). After being fed with canine blood
      containing 7500 microfilariae (mf) per mL, Cx. quinquefasciatus ingested
      approximately two times as many mf as Ae. albopictus (mean of 31.73 in comparison
      to 16.47). However, almost three times as many third-stage infective larvae
      developed in Ae. albopictus as in Cx. quinquefasciatus (mean of 3.25 as compared
      with 1.10), with a vector efficiency index (VEI) of 19.73 and 3.47, respectively.
      The results showed that Cx. quinquefasciatus and Ae. albopictus served as natural
      vectors of D. immitis in central Taiwan. Although Ae. albopictus was more
      efficient for heartworm transmission, Cx. quinquefasciatus may play a more
      prominent role on the transmission of dirofilariasis in central Taiwan.

PMID- 11297104
TI  - Effect of carbon dioxide on the Oriental cockroach Blatta orientalis.
AB  - Exposure to high concentrations of carbon dioxide (CO2) killed adult and nymphal
      stages of the oriental cockroach Blatta orientalis L. (Dictyoptera: Blattidae)
      with LT50 values of 11.5-16.2 h for 60% CO2 in air and 5.7-7.1 h for 100% CO2 at
      20 degrees C; corresponding LT50s at 28 degrees C were 2.8-4.6 h for 60% CO2 in
      air and 2.3-3.6 h for 100% CO2. Complete kill of mobile stages was obtained
      within 24 h using 60% CO2 at 20 degrees C. Survivors of treatments with 100% CO2
      at 28 degrees C remained completely paralysed for up to 3 days post-treatment and
      took up to 5 days to regain normal movement, but adult females then resumed
      production of oothecae with no significant loss in fecundity. Oothecae 5 or 30
      days after deposition required 60-84 h exposure to 60% CO2 at 20 degrees C to
      prevent emergence of nymphs but less time using 100% CO2 at 28 degrees C. At 28
      degrees C, when adult females were treated with 100% CO2 and 52% r.h. for 6 h
      (giving 100% mortality) loss of weight was significantly greater than that
      following treatment with air at 52% r.h. for 6 h (giving no mortality). However,
      significantly greater weight loss also occurred when they were treated with dried
      air (< 10% r.h.) for 6 h, also with no mortality. The toxicity of CO2 to mobile
      stages of the oriental cockroach appeared to result from irreversible effects on
      the nervous system, rather than from water loss during exposure.

PMID- 11297105
TI  - Control of flea populations in a simulated home environment model using
      lufenuron, imidacloprid or fipronil.
AB  - Control strategies were evaluated over a 6-month period in a home simulation
      model comprising a series of similar carpeted pens, housing matched groups of six
      cats, in which the life-cycle of the flea Ctenocephalides felis felis Bouche
      (Siphonaptera: Pulicidae) had been established. Additional adult fleas were
      placed on the cats at intervals to mimic acquisition of extraneous fleas from
      outside the home. Treatment strategies included a single subcutaneous deposition
      of injectable lufenuron supported by initial treatments with a short-acting
      insecticidal spray, or monthly topical applications of imidacloprid or fipronil.
      An untreated control group indicated that conditions were suitable for flea
      replication and development. Controls had to be combed on 18 occasions to remove
      excessive flea burdens and two developed allergic reactions. Lufenuron cats were
      combed once and required two insecticidal treatments in the first month to
      achieve control. Even so, small flea burdens were constantly present thereafter.
      Imidacloprid and fipronil treatments appeared to give virtually complete control
      throughout. Single fleas were found on imidacloprid cats on two occasions,
      whereas none were recovered from fipronil cats at any time after the first
      treatment. Tracer cats were used to monitor re-infestation rates at the end of
      the trial period. Small numbers of host-seeking fleas were demonstrated in all
      treatment pens, indicating that total eradication had not been accomplished. It
      is concluded that the home environment simulation model incorporating tracer
      animals could provide a powerful tool for studying flea population dynamics under
      controlled conditions but improved techniques are needed for quantifying other
      off-host life-cycle stages.

PMID- 11297106
TI  - Application of DNA markers to identify the individual-specific hosts of tsetse
      feeding on cattle.
AB  - Primer sets for five different ungulate loci were used to obtain individual
      microsatellite DNA profiles for 29 Mashona cattle from a herd in Zimbabwe. There
      were 3-13 alleles for each locus and, using the entire suite of five loci, each
      animal within the herd, including closely related individuals, could be
      unequivocally distinguished. Wild-caught Glossina pallidipes Austen (Diptera:
      Glossinidae) were fed on specific cattle and the bloodmeal was profiled 0.5-72 h
      after feeding. The individual specific sources of the bloodmeals, including mixe
      meals produced by allowing tsetse to feed on two different cattle, were reliabl
      identified up to 24 h after feeding. The technique was used in field studies of
      hos selection by G. pallidipes and G. morsitans morsitans Westwood (Diptera
      Glossinidae) attracted to pairs of cattle. When the pair comprised an adult and a
      calf, 100% of meals were from the adult. For some pairs of adult cattle, tsetse
      were biased significantly towards feeding on one animal, whereas for other pairs
      there was no such bias. In general, feeding was greater on the animal known to
      have lower rate of host defensive behaviour. Results suggest that relatively
      slight differences in the inherent defensive behaviour of cattle produce large
      difference in host-specific feeding rates when the hosts are adjacent. For flies
      attracted to pair of cattle, < 2% contained blood from both hosts. The DNA
      profiling technique will be useful in studying the epidemiology of vector-borne
      diseases of livestock.

PMID- 11297107
TI  - Use of deltamethrin 'pour-on' insecticide for the control of cattle
      trypanosomosis in the presence of high tsetse invasion.
AB  - A deltamethrin 'pour-on' insecticide was applied monthly to over 2000 cattle
      exposed to a high challenge of drug-resistant trypanosomes and high tsetse re
      invasion pressure in the Ghibe valley, south-west Ethiopia. Blood samples were
      taken monthly from an average of 760 cattle for determination of PCV and presence
      of trypanosomes. The area of the valley is approximately 350 km2 and the cattle
      grazed in roughly four locations covering about a quarter to half of the area.
      Two years before the trial commenced, Glossina morsitans submorsitans Newstead
      (Diptera: Glossinidae) began to invade the valley. Despite the use of the pour-on
      the mean apparent density of G. m. submorsitans continued to rise, and, during
      the 4 years of tsetse control, was more than three-fold higher than that recorded
      during the previous 18 months. Over the same period there was little change in
      the apparent density of Glossina pallidipes Austen (Diptera: Glossinidae). By
      contrast, the mean monthly prevalence of trypanosome infections in cattle over 36
      months of age decreased from 38.3 to 29.0%, the incidence of new infections
      decreased from 26.6 to 16.0% (a reduction of 40%), and packed cell volume in
      cattle increased from 21.7 to 24.1%. Evidence of a change in apparent parasite
      transmission rate was demonstrated by regression of infection incidence in cattle
      on the logarithm of apparent density of G. m. submorsitans. Before the trial
      started the regression coefficient was 45.8 +/- 6.3 and this reduced to 9.2 +/-
      2.5% incidence per log(e) (flies/trap/day) during the period of tsetse control.
      It was concluded that this indicated reductions in tsetse numbers in the
      immediate vicinities of cattle in a way that was not reflected in overall tsetse
      catches. Nevertheless, the comparatively high levels of trypanosome prevalence
      that persisted in the cattle demonstrates that, where invasion prevalence is
      high, treatment of small pockets of cattle will not eradicate tsetse. To achieve
      more significant reduction in trypanosome prevalence in cattle, integrated
      methods of control utilizing target barriers in the major routes of invasion will
      be needed.

PMID- 11297108
TI  - Olyset Net efficacy against pyrethroid-resistant Anopheles gambiae and Culex
      quinquefasciatus after 3 years' field use in C te d'Ivoire.
AB  - Pyrethroid-impregnated bednets are advocated for personal protection against
      malaria vectors. To avoid the need for periodic re-treatment, it would be
      advantageous to have nets that retain insecticidal efficacy for years and
      withstand repeated washing. Such a type of commercially produced bednet with
      permethrin 2% incorporated in polyethylene fibres (trademark Olyset Net supplied
      by Sumika Life-Tech Co., Osaka, Japan) was evaluated against mosquitoes in
      veranda-trap huts at Yaokoffikro, near Bouake, C te d'Ivoire, by standard WHOPES
      phase II procedures. Four Olyset Nets were compared with a standard untreated
      polyester net as control. They comprised three examples previously used in a
      village for over 3 years (one washed, one dirty, one very dirty) and a previously
      unused Olyset Net, newly unwrapped, from the same original batch. Bioassays with
      3 min exposure of susceptible Anopheles gambiae Giles (Diptera: Culicidae) gave
      >99% mortality of female mosquitoes tested on the 'new' Olyset Net. The used
      Olyset Nets gave mortality rates averaging 83% for the washed net, 85% for the
      dirty net and 55% for the very dirty net (within 24-h following 3 min exposure).
      Thus, Olyset Nets were found to remain remarkably effective against susceptible
      An. gambiae for at least 3 years under field conditions. Wild pyrethroid
      resistant populations of Culex quinquefasciatus Say and An. gambiae (savanna
      cytotype with 96% kdr) were assessed during June-August 1999 for their responses
      to sleepers protected by nets in the experimental huts. With regard to hut entry
      by foraging female mosquitoes, Olyset Nets showed some deterrency against An.
      gambiae (44% reduction by the new net, approximately 20% by the dirty nets, none
      by the washed net), but not against Cx. quinquefasciatus. Among mosquitoes
      entering the hut with untreated control net, 30-34% tried to leave (exophily) but
      were caught in the verandah trap. The permethrin repellency of Olyset Nets
      increased exophily by 19% for An. gambiae and 14% for Cx. quinquefasciatus. Blood
      feeding rates were 16% An. gambiae and 35% Cx. quinquefasciatus in the hut with
      sleeper under the untreated net (showing considerable prevention of biting), 22
      26% of both species in huts with washed or dirty used Olyset Nets (not
      significantly different from control), while the biting success rate of Cx.
      quinquefasciatus (but not kdr An. gambiae) was more than halved by the 'new'
      Olyset Net. Mortality rates of pyrethroid-resistant An. gambiae and Cx.
      quinquefasciatus from the huts were, respectively, 3% and 8% with the untreated
      polyester net, 27.5% and 17% with the 'new' Olyset, 15% and 17.5% with the washed
      Olyset, 16-25% and 17-20% with dirty old Olyset Nets. Kill differences between
      nets are significantly different for both An. gambiae and Cx. quinquefasciatus.
      Unfortunately the washed used Olyset Net showed least activity against resistant
      mosquitoes, despite its greatest activity against susceptible An. gambiae. In
      each case there was evidence that a high proportion of mosquitoes failed to feed
      through the net (many of them dying from starvation when they could not leave the
      closed hut), with indications that dirty Olyset nets enhanced this protective
      value.

PMID- 11297109
TI  - Economy class syndrome.

PMID- 11297110
TI  - Helping older people to remain in their own homes.

PMID- 11297111
TI  - Clinicians and guidelines: leading a horse to water..

PMID- 11297112
TI  - Advancing the field of clinical ethics: particularity and practicality.

PMID- 11297113
TI  - Incidence of nursing home placement in a defined community.
AB  - OBJECTIVE: To assess cumulative incidence and non-cognitive factors predicting
      nursing home placement in a defined older population. DESIGN AND SETTING: Six
      year follow-up of a population-based cohort living west of Sydney. PARTICIPANTS:
      3654 non-institutionalised residents aged 49 years or older (82.4% of those
      eligible) participated in baseline examinations during 1992 to 1994. MAIN OUTCOME
      MEASURES: Permanent nursing home admission for long-term institutionalised aged
      care in New South Wales, confirmed by records of approvals by the regional Aged
      Care Assessment Team and subsidy payments by government. RESULTS: After excluding
      384 participants who moved from the area or were lost to follow-up, 162
      participants (5.0%) had been admitted to nursing homes on a permanent basis by
      October 1999. Of participants who died since baseline, 20% had been admitted to a
      nursing home before death. Of those alive, 1.6% were current nursing home
      residents. Six-year cumulative incidence rates for nursing home placement were
      0.7%, 1.1%, 2.4%, 3.9%, 9.0%, 18.3% and 34.9% for people aged 55-59, 60-64, 65
      69, 70-74, 75-79, 80-84 and 85 years or older, respectively. Non-cognitive
      factors at baseline predicting subsequent nursing home admission included each
      additional year of age (risk ratio [RR], 1.14), fair or poor compared with
      excellent self-rated health (RR, 2.9, 3.6), walking difficulty (RR, 3.6) and
      current smoking (RR, 1.9). People owning their homes had a decreased likelihood
      of nursing home placement (RR, 0.6). CONCLUSIONS: Incidence rates of
      institutional aged care doubled for each five-year interval from the age of 60
      years. A range of non-cognitive factors predict nursing home placement.

PMID- 11297114
TI  - Compliance with guidelines for continuity of care in therapeutics from hospital
      to community.
AB  - OBJECTIVES: To evaluate compliance with the Australian Pharmaceutical Advisory
      Council's National guidelines to achieve the continuum of quality use of
      medicines between hospital and community. DESIGN: Descriptive survey, based on
      questionnaires filled out by general practitioners, of a sample of patients
      following recent discharge from public hospitals, collated with hospital record
      reviews for a 20% subsample of the patients. PARTICIPANTS AND SETTING: 357 GPs
      practising within the postcode boundaries of the South East Sydney Area Health
      Service were randomly selected to take part in the survey. Of 219 GPs who agreed
      to participate, 106 completed questionnaires on 203 patients. For a subsample of
      38 patients, hospital records were reviewed and compared with the GP survey data.
      RESULTS: For 52% (105/203) of all patients the GP was not notified of hospital
      admission. Medication management was documented in the discharge plan for 13%
      (5/38) of the subsample. Communication in both directions between GP and hospital
      about medications was recorded for 13% (5/38) of the subsample. Consultation with
      the GP about the patient's medication during the hospital stay occurred for 11%
      (22/203) of all patients and 24% (9/38) of the subsample. Ninety-one per cent of
      patients (185/203) were discharged with sufficient medication to last until they
      saw their GP. Fewer than 10% of patients received all the information the
      Guidelines require. For 33% (66/203) of the patients, GPs considered there was at
      least one barrier (eg, language, cultural) to understanding the medication
      regimen. CONCLUSIONS: Compliance with the Guidelines is not good at present.
      Their acceptance may be strengthened by formulating specific target indicators. A
      minimum indicator would be notifying the GP of three out of four matters: the
      patient's admission; medications on discharge; medication changes; and follow-up
      arrangements.

PMID- 11297115
TI  - Mortality and life-years lost due to alcohol: a comparison of acute and chronic
      causes.
AB  - OBJECTIVES: (i) To estimate the numbers of deaths and person-years of life lost
      (PYLL) due to high-risk alcohol consumption in Australia during 1997, using
      current estimates of consumption. (ii) To compare the number of deaths and PYLL
      due to acute conditions associated with bouts of intoxication and chronic
      conditions associated with long-term misuse of alcohol. METHODS: All Australian
      deaths during 1997 related to conditions considered to be partially or wholly
      caused by high-risk alcohol consumption were extracted from the Australian Bureau
      of Statistics Mortality Datafile and adjusted by alcohol aetiologic fractions
      calculated for Australia in 1997. A life-table method was used to estimate the
      PYLL for deaths from alcohol-caused conditions. MAIN OUTCOME MEASURES: Numbers of
      all deaths and PYLL due to chronic and acute alcohol-related conditions. RESULTS:
      Of the 3290 estimated alcohol-caused deaths in 1997, chronic conditions (eg,
      alcoholic liver cirrhosis and alcohol dependence) accounted for 42%, acute
      conditions (eg, alcohol-related road injuries and assaults) for 28% and mixed
      (chronic and acute) for 30%. Of the 62914 estimated potential life years lost,
      acute conditions were responsible for 46%, chronic for 33% and mixed for 21%. The
      average number of years of life lost through deaths from acute conditions was
      more than twice that from chronic conditions, because the former mostly involved
      younger people. CONCLUSIONS: In view of the societal burdens imposed by premature
      deaths, more effective public health strategies are needed to reduce the harm
      associated with occasional high-risk drinking (as well as sustained high-risk
      drinking), especially among young people.

PMID- 11297116
TI  - Operative photography in gynaecological endosurgery.
AB  - OBJECTIVES: To define the attitude of patients, doctors and nurses to operative
      photographs captured at gynaecological endosurgery, and to determine the value of
      these photographs in patient education. DESIGN AND SETTING: Postal questionnaire
      survey of specialists, general practitioners, nurses and patients at a tertiary
      referral hospital in south-west Sydney. PARTICIPANTS: All patients who underwent
      endoscopic gynaecological surgery between 1 February and 1 May 1998, and for whom
      good quality operative photographs were available, and medical and nursing staff
      randomly selected from lists of practitioners within the Southwest Sydney Area
      Health Service. MAIN OUTCOME MEASURES: Opinions on whether operative
      photodocumentation assists patients in understanding their condition; the value
      to patients of these records; whether operative photographs assist referring
      doctors in subsequent management of patients; the use of operative photographs in
      medical records or as personal records for patients; whether photographs may lead
      to anxiety or be used in medicolegal action. RESULTS: All patients believed
      operative images were valuable in helping them understand their condition. 19 of
      20 specialists (95%), 85 of 123 general practitioners (69%) and 23 of 28 nursing
      staff (82%) also believed that operative images assist patients in understanding
      their disease. Nearly all patients denied that operative images would create
      anxiety, and specialists, general practitioners and nurses also felt that the
      photographs would not cause anxiety. 78% of general practitioners expressed a
      desire to receive operative images. CONCLUSIONS: Photographic records of
      operative procedures are regarded as valuable by both referring doctors and their
      patients. Patients find photographs useful in understanding their disease.

PMID- 11297117
TI  - The management of varicella-zoster virus exposure and infection in pregnancy and
      the newborn period. Australasian Subgroup in Paediatric Infectious Diseases of
      the Australasian Society for Infectious Diseases.
AB  - Zoster immunoglobulin (ZIG) should be offered to pregnant, varicella-seronegative
      women with significant exposure to varicella-zoster virus (VZV) (chickenpox)
      infection. Oral aciclovir prophylaxis should be considered for susceptible
      pregnant women exposed to VZV who did not receive ZIG or have risk factors for
      severe disease. Intravenous aciclovir should be given to pregnant women who
      develop complicated varicella at any stage of pregnancy. Counselling on the risk
      of congenital varicella syndrome is recommended for pregnant women who develop
      chickenpox. ZIG should be given to a baby whose mother develops chickenpox up to
      7 days before delivery or up to 28 days after delivery. Intravenous aciclovir
      should be given to babies presenting unwell with chickenpox, whether or not they
      received ZIG. Breastfeeding of babies infected with or exposed to VZV is
      encouraged. A mother with chickenpox or zoster does not need to be isolated from
      her own baby. If siblings at home have chickenpox, a newborn baby should be given
      ZIG if its mother is seronegative. The newborn baby does not need to be isolated
      from its siblings with chickenpox, whether or not the baby was given ZIG. After
      significant nursery exposure to VZV, ZIG should be given to seronegative babies
      and to all babies born before 28 weeks' gestation.

PMID- 11297118
TI  - Evidence-based medicine: how good is the evidence?
AB  - The "evidence" in EBM must be of high quality in order to be useful, but this is
      not always the case. Even the "gold standard" of evidence-based medicine, the
      randomised clinical trial, is bedevilled by low inclusion rates and potentially
      important recruitment biases. "Real world" trials often do not give the same
      results as these highly artificial controlled clinical studies. Meta-analysis,
      the next most important level of evidence in EBM, may be unreliable, sometimes
      giving different results to subsequent large randomised trials. There is a bias
      in the hypotheses tested in large clinical trials, as the costs involved are
      usually covered by commercially interested companies. For this reason, trials of
      non-patentable compounds or therapies of no commercial interest may not be
      performed. The process of journal review and publication is capricious, slow and
      may have a selection bias towards positive studies, meaning that communication
      channels for the "evidence" are often unsatisfactory. For many rarer conditions
      and situations, there is simply no "high level" evidence, such as in paediatrics
      and subspecialty surgery.

PMID- 11297119
TI  - Confidentiality.
AB  - Issues of confidentiality are complicated by the relationships we have to
      patients and others who have valid interests in the confidential information.
      There are no straightforward answers to problems which involve complex
      relationships and sensitive information. The best we can do is to think
      thoroughly and carefully about the issues in each case, and use our knowledge of
      the people involved to reach a decision. Doctors faced with difficult decisions
      of this kind should be assured that everyone finds them difficult. Sharing the
      burden with experienced colleagues can be helpful.

PMID- 11297120
TI  - Screening for colorectal cancer: what is the most cost-effective approach?
AB  - In Western countries, including Australia, colorectal cancer is the leading cause
      of cancer mortality in nonsmokers. Development of most colorectal cancers can be
      prevented by adenoma removal. The current screening strategies of faecal occult
      blood testing (FOBT), flexible sigmoidoscopy combined with FOBT and colonoscopy
      are all cost effective. In clinical practice, a range of options should be
      offered to allow for individual patients' preferences. A public education program
      is essential to the success of any screening strategy.

PMID- 11297121
TI  - SIDS: more facts and controversies.
AB  - A more robust theory of the causation of sudden infant death syndrome (SIDS) is
      needed. The asphyxial theory of SIDS, which encompasses the prone sleeping
      position, relies on contradictory pathological evidence and fails to explain
      infants with SIDS who are found in the supine or lateral position. Many of the
      risk factors for SIDS point to an infective cause. The relative risks of these
      infection-related factors differ from study to study, as does the relative risk
      of prone sleeping position. I present the case for an infection model for SIDS
      causation, which has largely been neglected by mainstream SIDS researchers.

PMID- 11297122
TI  - Is isopropyl alcohol swabbing before injection really necessary?

PMID- 11297123
TI  - Patients need greater access to autologous blood.

PMID- 11297125
TI  - Fees for autologous blood are excessive.

PMID- 11297124
TI  - Autologous donation is not cost-effective.

PMID- 11297126
TI  - Transfusion practices must be evidence-based.

PMID- 11297127
TI  - We need better monitoring of the use of blood products.

PMID- 11297128
TI  - Non-acute transfusions for ambulatory patients.

PMID- 11297129
TI  - Clinical role of quantitative ultrasound in the assessment of osteoporosis in
      individual patients.

PMID- 11297130
TI  - Rubella vaccination in prenatal and postnatal women: why not use MMR?

PMID- 11297131
TI  - A randomised crossover trial of chemotherapy in the home: patient preferences and
      cost analysis.

PMID- 11297132
TI  - A randomised crossover trial of chemotherapy in the home: patient preferences and
      cost analysis.

PMID- 11297133
TI  - Disruptive doctors.

PMID- 11297134
TI  - Disruptive doctors.

PMID- 11297135
TI  - Headache and face pain.

PMID- 11297136
TI  - Screening of gamete donors for cystic fibrosis.

PMID- 11297137
TI  - Emergency department observation wards.

PMID- 11297138
TI  - Economic sanctions and public health--the case of Cuba.

PMID- 11297139
TI  - Patient safety: a fence at the top of the cliff?

PMID- 11297140
TI  - Mountaineering fatalities in Mt Cook National Park.
AB  - AIM: To estimate the risk of death associated with mountaineering in the Mt Cook
      National Park (MCNP), and to describe some characteristics of the fatal events.
      METHODS: Fatality data, including coroners' files, were obtained from the
      Mountain Safety Council and the Department of Conservation, Mt Cook field office.
      Data on occupancy of mountain huts were used to estimate rates. RESULTS: 33
      deaths occurred among climbers using the alpine huts studied, over a period in
      which climbers spent 52 906 nights in the huts. The overall fatality rate was
      0.62/1000 hut nights. This is estimated to equate with a fatality rate of
      1.87/1000 climbing days. Fatality risk estimates varied more than 50-fold between
      huts serving the highest risk (6.5/1000 days) and lowest risk (0.3/1000 days)
      climbing areas within the MCNP. CONCLUSION: The risk of death associated with
      mountaineering in MCNP varies greatly with the difficulty and seriousness of the
      climbing undertaken. The risk associated with the more serious climbing in MCNP
      is very similar to that reported for climbers on expeditions to extreme altitude.
      Even the lower risk estimates are very high when compared with those for most
      other recreational activities.

PMID- 11297141
TI  - Nicotine in hair of bar and restaurant workers.
AB  - AIM: To measure the relation between workplace smoking policies and exposures to
      Environmental Tobacco Smoke (ETS) of workers in bars and restaurants. METHODS:
      114 workers in Wellington and Auckland were questioned about sources of exposure
      to ETS and smoking habits, and details of the smoke-free policy in their work
      place were recorded. A hair sample was collected from each participant and tested
      for nicotine. RESULTS: Among non-smoking workers, hair nicotine levels varied
      strongly according to the smoke free policy at their place of work (Kruskall
      Wallis, chi2 = 26.38, p < 0.0001). Those working in 100% smoke free restaurants
      had much lower levels than staff working in bars with no restrictions on smoking,
      and levels were intermediate for staff working in places with a partial smoking
      ban. These findings were not changed when adjustments were made for other sources
      of ETS exposure. Hair nicotine levels among nonsmokers working in places with no
      restriction on smoking were similar to hair nicotine levels of active smokers.
      CONCLUSION: The present New Zealand Smoke Free Environment Act does not protect
      workers in the hospitality industry from exposure to ETS. The findings from this
      study highlight the substantial levels of exposure of bar and restaurant staff
      from patrons' smoking.

PMID- 11297142
TI  - Presenting features of meningococcal disease, public health messages and media
      publicity: are they consistent?
AB  - AIMS: To investigate whether the presenting features of meningococcal disease as
      promoted in public health awareness material and in the print media accurately
      reflect the clinical features in patients admitted to Auckland hospitals with
      meningococcal disease January 1998 to June 1999. METHODS: Hospital record, public
      health message and newspaper article review, with analysis by presenting feature,
      age group and disease complex. RESULTS: The most common presenting features were
      fever (95%), rash (65%), vomiting and nausea (64%), lethargy (62%), headache
      (44%), refusing food and drink (35%), irritability (33%), muscle ache and joint
      pains (27%) and stiff neck (26%). Public health messages gave appropriate
      emphasis to the key features, whereas newspaper articles under-emphasised these.
      The term 'meningitis' was used more frequently in newspapers (65%) than in public
      health messages (30%), despite meningitis alone presenting less frequently (38%
      of cases) than meningococcal septicaemia, and having a less serious prognosis.
      CONCLUSIONS: Presenting features currently noted in the Ministry of Health's
      health education resource material are appropriate. Public health specialists
      dealing with the media should ensure that appropriate messages are incorporated
      into media reports. A greater use of the term 'meningococcal disease' by both
      public health agencies and media would convey to the public the message that this
      disease has a spectrum of presenting features, with those of septicaemia more
      common, but also indicating an even greater need for urgency of action than with
      'classical' meningitic features.

PMID- 11297143
TI  - Assessing ethnicity in New Zealand health research.
AB  - AIMS: To investigate the patterns and criteria reported for categorisation of
      ethnicity in a sample of health research reports which made comparisons between
      Maori and non-Maori. METHODS: A total of 98 research reports, which made
      comparisons between Maori and non-Maori samples, were selected from the New
      Zealand Medical Journal over five 12-month periods and one 24-month period
      between 1980 and 1996. RESULTS: Only 19% of the 98 articles reported any
      information about the criteria used for categorising ethnicity. Only three
      articles mentioned how people of dual or multiple ethnicity were categorised.
      Although the term 'race' was commonly used in the 1980s, the terms 'ethnicity'
      and 'ethnic group' were more widely used later to describe ethnicity.
      CONCLUSIONS: Much of the New Zealand research comparing Maori and non-Maori
      samples is likely to have unacknowledged error. Most articles did not meet
      minimum expected standards for reporting procedures for categorising ethnicity.
      There seemed to be little awareness of the major changes which have taken place
      in the New Zealand Census question concerning ethnicity between 1981 and 1996.
      Some suggestions were made for effective practice when assessing and reporting
      ethnicity in New Zealand research.

PMID- 11297144
TI  - Evidence databases, the Internet, and general practitioners: the New Zealand
      story.
AB  - AIM: To determine self-reported access to and use of the Internet and the
      Cochrane Library by general practitioners (GPs) in New Zealand. METHODS: A
      national cross sectional postal and fax survey of randomly selected GPs. RESULTS:
      A total of 381 of 459 eligible GPs returned completed questionnaires (83%). The
      mean age of this sample was 45.7 years (SD 8.6) and average years in general
      practice was 15.7 years (SD 8.8 years). 74% (277) were male and 77% (289) in full
      time practice. Internet access was present in 40% (95% CI 36-46%) of practices
      and 76% (72-81%) of GP's homes. The majority, 56% (51-61%), of GPs had used the
      Internet with regard to a patient. Younger GPs (<35 years old OR = 2.69, 95% CI
      1.10-6.60) and male GPs (OR 1.72, 95% CI 1.02-2.90) were significantly more
      likely to report use of the Internet with respect to patients. 42% (95% CI 37
      47%) of GPs were aware of the Cochrane Library but only 15% (11-19%) had used it.
      Those in group practice were more likely to be aware of the Cochrane database
      (adjusted OR 1.85, CI 1.09-3.12). CONCLUSIONS: Internet use is prevalent among
      GPs. Solo practitioners, older GPs and female GPs are least likely to avail
      themselves of this resource. Although half of GPs knew about Cochrane, a minority
      used it. Access and use of evidence databases can be improved in New Zealand.
      Strategies to assist those least likely already to use Cochrane may help our
      collective efforts towards evidence based practice.

PMID- 11297145
TI  - Looking forward to health needs assessments: a new perspective on 'need'.

PMID- 11297146
TI  - Responsibilities of doctors in management and governance.

PMID- 11297147
TI  - Methylprednisolone use in acute spinal cord injury.

PMID- 11297148
TI  - Duct detection and wall spacing estimation in breast tissue.
AB  - The relationship between duct tissue and several types of malignant disease
      suggests that methods for characterizing duct structures may be useful tools in
      ultrasonic tissue characterization. This paper presents performance results from
      ultrasonic phantom experiments and Monte Carlo simulations for detecting and
      estimating duct wall spacings on the order of those typically found in breast
      tissue using methods based on the generalized spectrum (GS) and cepstrum. A
      performance comparison demonstrates the advantages of each method and examines
      the effects of various signal processing options, including a special
      normalization technique for the GS that effectively whitens the data spectrum and
      reduces interfering spectral influences with little overall performance loss.
      Experimental results (for both simulation and phantom) indicate that the GS
      typically achieves detection rates of over 90% (at 10% false alarm rates) over a
      broad range of SNR values (3-21 dB). The GS detection performance exceeds that of
      the cepstrum and exhibits more robustness to noise and signal processing
      parameters. Simulation results with fixed system effects indicate better
      estimation performance for cepstral-based methods, while experimental phantom
      results show the GS estimation performance to be the same or better than the
      cepstral-based method.

PMID- 11297149
TI  - Theoretical bounds on the estimation of transverse displacement, transverse
      strain and Poisson's ratio in elastography.
AB  - The Cramer-Rao Lower Bounds (CRLB) are derived for the displacement and strain
      estimation in directions orthogonal to the ultrasonic beam axis, using a
      previously-described recorrelation method of axial, lateral and elevational
      motion estimation. We also compare it to the lateral tracking method that
      involves the sole use of the axial signal in the transverse direction. Our
      theoretical results, verified with simulations and phantom experiments, show that
      elastography is capable of measuring axial and transverse strain at up to 10%
      axially applied compression. Finally, we predict the performance of the
      estimation of the Poisson's ratio using decoupled axial and lateral estimates
      that result from the recorrelation method.

PMID- 11297151
TI  - Prevalence of asthma-associated symptoms in Turkish children.
AB  - The aim of the first national cross-sectional survey was to determine the
      prevalence of asthma-like respiratory symptoms and the associated risk factors
      among children aged 0-17 via interview with the parents by primary care
      physicians. They were selected through stratified two-stage cluster probability
      sampling in urban and rural parts of randomly selected 27 of 81 administrative
      districts in Turkey. Data was collected for 46,813 children (23,512 males and
      23,301 females) of whom 66 percent resided in urban areas. The prevalence of
      physician-diagnosed asthma was 0.7 percent. The lifetime and current (last 12
      months) prevalences were 14.7 percent and 2.8 percent for asthma, and 15.1
      percent and 3.4 percent for wheezing respectively. The presence of personal atopy
      and history of family atopy were the most significant risk factors for current
      prevalences of wheezing, and asthma [adjusted Odds ratios (OR) and 95% confidence
      intervals (CI) were 6.2 (CI=4.0-9.5) and 1.8 (CI=1.3-2.4) for wheezing, and 8.5
      (CI=5.6-12.9) and 1.9 (CI=1.4-2.5) for asthma, respectively]. Though there were
      no significant differences among those residing in urban versus rural areas
      regarding the current prevalences of asthma and wheezing, those living in coastal
      areas had considerably higher current prevalences than those inland (OR=2.6,
      CI=1.9-3.5 for wheezing, and OR=2.3, CI=1.7-3.1 for asthma). Residence in
      northern Turkey appeared to be a significant risk factor for wheezing (OR=1.9,
      CI=1.4-2.5), and children resident in southern Turkey exhibited the highest risk
      for occurrence of asthma (OR=1.5, CI=1.1-2.0) compared with eastern Turkey. In
      conclusion, the respiratory symptoms associated with asthma were an important
      cause of morbidity in childhood in Turkey. The discrepancy between prevalence of
      physician-diagnosed asthma and lifetime and/or current asthma prevalence figures
      may reflect the reluctancy of both physicians and parents to diagnose this
      condition. Besides strongest associations with personal atopy and atopic
      heredity, there were significant differences in prevalence rates between children
      residing in different regions, supporting the role of environmental factors.

PMID- 11297150
TI  - Reconstructive ultrasound elasticity imaging for renal transplant diagnosis:
      kidney ex vivo results.
AB  - It may be possible to diagnose and monitor scarring, inflammation and edema in
      transplant kidney using reconstructive ultrasound elasticity imaging. Kidney
      elasticity is expected to change dramatically with scar, and to a lesser degree,
      with acute inflammation and edema. The hypothesis that changes in kidney
      elasticity can be imaged using a clinical ultrasound scanner was experimentally
      tested with an ex vivo canine kidney model, and results on a single pair of
      kidneys are reported in this paper. A cross-linking agent affected kidney
      elasticity both globally and locally. Elasticity changes were monitored with
      accurate estimates of internal displacement and strain followed by Young's
      modulus reconstruction. The results of this study strongly suggest that
      ultrasound elasticity imaging can detect elasticity changes in complex structures
      such as the kidney. Moreover, it has the potential to become an important
      clinical tool for renal transplant diagnosis.

PMID- 11297152
TI  - Transcatheter closure of secundum atrial septal defects, a ventricular septal
      defect, and a patent arterial duct.
AB  - We report our clinical experience with the newly developed Amplatzer device in
      transcatheter closure of nine atrial septal defects (ASDs), one ventricular
      septal defect (VSD), and one patent arterial duct (PDA). Eleven patients with ASD
      (age range 2.5-18 years) selected according to the location and size of the
      defect by transesophageal echocardiography (TEE), a five-year-old patient with
      muscular VSD and a one-year-old patient with PDA were considered for
      transcatheter closure with Amplatzer devices. All procedures were performed under
      general anesthesia with fluoroscopic and TEE guidance, following a routine
      hemodynamic evaluation in the catheter laboratory. The optimal device size was
      selected after the balloon sizing of the ASDs. The sizes of the VSD and PDA were
      measured on TEE and angiography. The patients were discharged at 24 hours, after
      an evaluation with x-ray, electrocardiogram (ECG), and echocardiography; they
      were on 3-5 mg/kg/day aspirin and infective endocarditis prophylaxis for six
      months after the procedure. They were reassessed at six to eight weeks and Holter
      monitoring was done in addition. Devices were used for nine ASD patients, and for
      the VSD and the PDA patients. Mean ASD size was 14.3 +/- 5.3 mm at TEE and 18.3
      +/- 4.3 mm at balloon sizing (p=0.02). The mean size of the device was 18.7 +/-
      4.2 mm. The procedure time and the fluoroscopy time were 46.1 +/- 12.3 and 12.9
      +/- 1.6 minutes, respectively. Immediately after the procedure, four patients
      (44%) had trivial shunts (TS). TS remained in only two during discharge, and no
      shunt was observed at second evaluation. The devices were similarly applied to
      VSD (12-7 mm) and PDA (8-6 mm) patients. Both cases had TS immediately, which
      disappeared at 24 hours. None of the patients had major complications. Junctional
      rhythm developed in one patient, and another patient had frequent
      supraventricular extrasystoles. Amplatzer is an effective and safe device for
      transcatheter closure of ASD, VSD, or PDA, especially in pediatric patients.

PMID- 11297153
TI  - Why hypothermia in neonatal hypoxic ischemic encephalopathy?
AB  - The incidence of asphyxiated full-term infants is still high in both high income
      and developing countries. In up to 80 percent of infants, moderate to severe
      birth asphyxia results in long-term neurological sequelae. Many years of
      experimental work and a limited data on hypoxic-ischemic neonates have supported
      the hypothesis that hypothermia after the primary insult induces permanent
      neuroprotection. In this mini overview, we attempt to update pediatricians in
      this aspect and raise the following: Will the future treatment include
      hypothermia along with the conventional and or other promising drugs affecting
      different aspects of the hypoxia-ischemia?

PMID- 11297154
TI  - HLAs in children with minimal change disease and other types of nephrotic
      syndrome in the southern part of Turkey.
AB  - The aim of this study was to investigate the human leukocyte antigen (HLA)
      profile of children with nephrotic syndrome in the southern part of Turkey.
      Seventy-eight children with nephrotic syndrome were studied for the frequency of
      class I and class II human leukocyte antigens. Forty-seven of them were steroid
      sensitive nephrotic syndrome (minimal change disease-MCD) and 31 were other types
      of nephrotic syndrome. The results were compared with 133 healthy subjects for
      HLA groups. HLA B13, Cw5, Cw7, DR4, DR7, DRw10, Drw15(2) and DQ2 in the MCD group
      and HLA A31, B8, B13, B17, Cw2, Cw6, Cw7, DRw10 and DRw12 in the non-MCD group
      were found significantly increased when compared to healthy controls. MCD
      patients with frequent relapses had higher frequencies of both Cw6 and DR1 (p <
      0.005) and MCD patients with infrequent relapses had a higher frequency of Cw7 (p
      < 0.05). In conclusion, HLA groups may help in the early diagnosis of these
      variants.

PMID- 11297155
TI  - Combined use of chemotherapy and 131I-metaiodobenzylguanidine in the treatment of
      advanced-stage neuroblastoma.
AB  - Despite intensive chemotherapy, surgery and/or radiation, prognosis continues to
      be very poor in disseminated neroblastoma. Owing to neuroblastoma sensitivity
      progress might be achieved with high-dose radiation. Metaiodobenzyl guanidine
      (MIBG) coupled with 131I provides the opportunity for highly selective radiation
      treatment of neuroblastoma, which could potentially deliver five to 10 times the
      dose of conventional external-beam treatment without specific tissue toxicity. To
      improve the long-term results in advanced-stage neuroblastoma, we integrated this
      new treatment modality with conventional chemotherapy. Eight neuroblastoma
      patients refractory to conventional treatment were treated with 131I-MIBG
      chemotherapy (vincristine, VP16, iphosphamide, carboplatin, epirubicin,
      cyclophosphamide) combination. Five of the eight patients responded to 131I-MIBG
      treatment (2 complete and 3 partial responses). There were also three patients
      with stable disease. Median survival was 48 months (range 1 to 84 months), and
      five patients relapsed in their follow-up and died of progressive disease. We
      concluded that a combined 131I-MIBG and chemotherapy approach is useful in
      advanced-stage neuroblastoma patients, with considerably less side effects.
      Although survival is improved when compared to conventional treatment, the
      overall prognosis is still poor. More lethal radionuclide conjugation to MIBG
      which will deliver higher tumor and lower critical organ doses may offer the best
      solution for targeted radionuclide therapy of neuroblastoma.

PMID- 11297156
TI  - The role of pulmonary artery anatomy in repair of tetralogy of Fallot.
AB  - Pulmonary artery anatomy is the key factor that determines the type of surgical
      treatment required in tetralogy of Fallot. Despite the fact that routine primary
      repair is now done on infants, inadequate pulmonary artery size can dictate the
      need for staged surgical repair in even the oldest age groups. From October 1986
      to October 1998, 361 patients at our clinic underwent surgery to correct
      tetralogy of Fallot. A total of 292 cases were treated with primary repair, 69
      surgeries were palliative, and 30 of these 69 underwent corrective surgery. The
      Nakata index was used as a pulmonary artery index (PAI), and PAI< 200 was the
      criterion for requirement of two-stage repair. Of the 30 patients that underwent
      staged repair, the Blalock-Taussig shunt (BTS) procedure was used in 24; the
      remaining six patients had right ventricular outflow tract reconstruction
      (RVOTR). The mean age of all the palliative surgery patients was 3.4 years (range
      6 months to 11 years), and of those who received corrective surgery was 5.5 years
      (range 2-12 years). These patients' PAI values were 181 +/- 37.5 mm2/m2 and 359
      +/- 130.7 mm2/m2, respectively. The period between the two operations ranged from
      two months to four years. Mortality rates were 2.8 percent for palliative surgery
      as a whole, 4.1 percent for primary repair, and 16.6 percent for staged repair.
      Our policy with regard to corrective surgery for tetralogy of Fallot is to do
      primary repair regardless of a patient's age and weight, except in cases where
      the pulmonary artery anatomy is appropriate for the patient's body size.

PMID- 11297157
TI  - Enuresis: point prevalence and associated factors among Turkish children.
AB  - The aim of this study was to establish the prevalence and associated factors of
      enuresis nocturna and to better understand nocturnal bladder control in Turkish
      children. A randomized epidemiological study was performed among primary school
      children, aged four to 12 years, living in Aydin, Turkey. After data collection
      via a self-administered questionnaire completed by the parents, data of 2,300
      children were accepted for the analysis. The overall prevalence of reported
      marked nocturnal enuresis (at least weekly) was 11.6 percent and of day wetting
      0.8 percent. Enuresis was more frequent in boys than in girls. Age, family
      history of enuresis, large family size, urinary tract infections and low parental
      socioeconomic class were all statistically associated with reported enuresis
      nocturna. Familial history among the enuretics and non-enuretics was 40.7 percent
      and 9.5 percent, respectively. Of the enuretics, 11 percent were treated
      professionally, 65 percent were treated traditionally by the family and 25
      percent sought no help to manage the enuresis. A reference age of 2.9 +/- 1.6
      years was calculated for nocturnal bladder control of the children studied. These
      results suggest that prevalence of enuresis nocturna and development of bladder
      control in Turkish children are not so different from that seen in other European
      and Middle East countries, and that the most significant factors associated with
      enuresis are socioeconomic and familial ones. Turkish families do not have a high
      level of concern about enuresis, even in the older children. This study
      demonstrated that enuresis is a sizable problem in Turkey and that a great
      ignorance about enuresis by both parents and physicians exits.

PMID- 11297158
TI  - MR imaging of pelvic and thigh muscles in congenital muscular dystrophy.
AB  - To define and compare the magnetic resonance (MR) imaging findings of pelvic and
      thigh muscles in merosin-deficient and merosin-positive congenital muscular
      dystrophy, 10 patients with merosin-positive and six patients with merosin
      deficient muscular dystrophy were examined in a 0.5 T MR imaging unit. Intensity
      and atrophy scores were given to individual muscles by two radiologists and were
      calculated for three muscle groups (pelvic, anterior thigh and posterior thigh
      muscles). Rectus femoris was affected less than the vastus muscles in 40 percent
      of cases in merosin-positive patients, whereas there was no selective sparing in
      merosin-deficient patients. Sartorius and gracilis were relatively spared in both
      groups. The most consistently affected muscles were gluteus maximus, adductor
      magnus and brevis in merosin-positive patients. Atrophy was more prominent in the
      adductor muscles in the merosin-deficient group. Intensity scores of anterior
      thigh muscles of the merosin-positive group were significantly higher than those
      of the merosin-deficient group (U = 8, p = 0.016). When stepwise logistic
      regression model was applied, intensity score of the anterior thigh muscles was
      found to be the best differentiating variable. The regression analysis model
      formed was able to differentiate the two forms with a sensitivity of 80 percent
      and specificity of 83 percent.

PMID- 11297159
TI  - Diastolic forward blood flow in the pulmonary arteries of normal children: a
      Doppler echocardiographic study.
AB  - Pulmonary arterial flow was examined in 60 normal children with a mean age of 8.5
      +/- 3.7 years (range 3.3 to 17.9 years) and mean body surface area of 0.95 +/-
      0.3 m2 (range 0.6 m2 to 1.7 m2) by pulsed Doppler echocardiography. Two distinct
      antegrade waveforms during diastole were detected. The peak velocities of early
      diastolic forward flow ranged from 20 to 30 cm/s (mean 26 +/- 4) and the late
      diastolic forward flow ranged from 16 to 29 cm/s (mean 23 +/- 3). The integrals
      of early diastolic forward flow ranged from 2.1 to 4.7 cm (mean 3.1 +/- 0.7) and
      late diastolic forward flow ranged from 1 to 3.6 cm (mean 2.1 +/- 0.7). Duration
      of early diastolic forward flow ranged from 161 to 256 ms (mean 187 +/- 29) and
      late diastolic forward flow ranged from 82 to 188 ms (mean 133 +/- 29). Data
      analysis for age indicated no significant difference in these measurements
      between children three to nine years old (n = 33) and children 9.1 to 18 years
      old (n = 27). The effect of respiration was observed in 10 randomly chosen
      subjects (mean age 8.6 +/- 4.1 years). Although early and late diastolic peak
      forward flow velocities, flow velocity integrals and flow duration during
      inspiration tended to be larger than during expiration, only late diastolic peak
      forward flow velocities during inspiration were significantly larger than during
      expiration (24.2 +/- 3.2 versus 18.2 +/- 3 cm/s, p = 0.001). This study defines
      normal Doppler ultrasound pulmonary arterial flow velocities, flow velocity
      integrals and flow duration during diastole in normal children. These results can
      be used for comparison with patterns found in disease states.

PMID- 11297160
TI  - Pediatricians' opinions about the problems between the departments of pediatrics
      and child psychiatry and possible solutions.
AB  - The necessity of collaboration between the Departments of Pediatrics and Child
      Psychiatry is an accepted idea. However, relevant literature reveals that
      collaboration between the two departments is not satisfactory. Rearrangement of
      relations between the two departments in Hacettepe University Ihsan Dogramaci
      Children's Hospital has been designated a goal. An education program will be
      planned accordingly. A questionnaire was designed to determine 65 pediatricians'
      knowledge, thoughts, expectations and needs about collaboration between the two
      departments; all were working in Hacettepe University Children's Hospital, in
      inpatient services, outpatient clinics or emergency services. An education
      program for consultation-liaison activities has been constituted to achieve the
      desired results. Efficacy of the program was discussed considering the features
      and tendencies of the two departments.

PMID- 11297161
TI  - Endovascular stent implantation in congenital heart defects.
AB  - We report the immediate and short-term results of endovascular stent
      implantations from our center. We performed stent implantations in four patients
      (3, 12, 18 and 20 years old) with different stenoses or obstructions: right
      ventricular outflow conduit obstruction, left Blalock-Taussig obstruction, post
      operative recoarctation and cavopulmonary anastomosis obstruction. Stent were
      implanted successfully. The mean diameters of stenoses were expanded from 4.5 +/-
      3.5 (2-7) mm to 9 +/- 1. 2 (8-10) mm, and the complaints of patients were
      improved significantly by stent implantation. There was no complication related
      to the procedures. All patients are living except one who died from
      cerebrovascular event unrelated to the stent implantation. The mean follow-up
      period of three living patients is 6.3 +/- 5.5 (1-2) months. As of the last
      control, all have remained at the caliber achieved at original placement. In
      light of our limited experience and previous reported studies, we conclude that
      intravascular stents are safe and can be used effectively in selected patients
      with congenital heart defects.

PMID- 11297162
TI  - Henna-induced hemolytic anemia and acute renal failure.
AB  - Henna is a traditional cosmetic agent and is used worldwide, especially in the
      Middle East. Its active agent is lawsone (2-hydroxy-1,4-naphthoquinone). Henna is
      not only applied to hands or hair as a cosmetic agent in traditional ceremonies,
      but is also applied to the body on lesions in the treatment of seborrheic
      dermatitis or fungal infections. However, its application over the body or in
      newborns is rare. Here we report a 27-day-old boy who developed hemolytic anemia
      and acute renal failure following topical application of henna to his abdomen,
      intertriginous region and legs to treat diaper rash.

PMID- 11297163
TI  - Antenatal diagnosis of postductal coarctation of the aorta. A case report.
AB  - Fetal echocardiography can be used to detect congenital heart disease prenatally
      with a high degree of accuracy, and complex heart malformations have also been
      clearly described in the fetus. However, it is difficult to diagnose correctly or
      to exclude definitely aortic coarctation by fetal echocardiography. A 23-year-old
      woman was referred for fetal echocardiographic examination at 21 weeks' gestation
      after discovery of hydrops fetalis (nonimmune) on an obstetric ultrasound
      examination. Aortic isthmus appeared hypoplastic with a diameter < or = 3rd
      percentile for gestational age. There was a narrowing within the descending aorta
      immediately distal to the origin of the ductus arteriosus. Color flow imaging
      demonstrated acceleration and turbulent flow and the peak pressure gradient was
      measured 83 mmHg by continuous wave Doppler in the same area. The pregnancy
      terminated in spontaneous abortion at 22 weeks' gestation. The fetus was
      stillborn. The autopsy findings confirmed the prenatal diagnosis. We conclude
      that together with the quantitative estimation of the aortic arch, color Doppler
      and continuous wave Doppler are helpful in diagnosis and estimation of the
      pressure gradient.

PMID- 11297164
TI  - Pseudohypoparathyroidism type IA and II with severe neuropsychic manifestations.
AB  - Pseudohypoparathyroidism (PHP) is characterized by unresponsiveness of target
      tissues to the biological actions of the parathyroid hormone (PTH), with
      resulting hypocalcemia and hyperphosphatemia, despite the elevated serum levels
      of PTH. PHP is divided into types Ia, b, c and II, depending on the presence of
      Albright's hereditary osteodystrophy (AHO), defective urinary excretion of
      phosphate (U-P) and response in urinary excretion of cyclic adenosine
      monophosphate (U-cAMP) after the administration of exogenous PTH. Patients with
      PHP might exhibit various manifestations of neuropsychic disturbances. We present
      two boys, aged 14 and 16 years, both with paresthesia, anxiety and epilepsy; the
      former patient also suffered from mild mental retardation. In both patients,
      hypocalcemia and hyperphosphatemia together with increased serum levels of PTH
      suggested the diagnosis of PHP. After administration of exogenous PTH (Ellsworth
      Howard test), there was a drop in U-P in both patients, while U-cAMP was
      decreased in the first patient and increased in the second one, thus confirming
      the diagnoses of PHP Ia and II, respectively. Neuropsychic disturbances and
      epilepsy resolved completely in both patients after treatment with calcium and
      dihydrotachysterol. Evaluation of calcemia and phosphatemia should be mandatory
      in all patients with neuropsychic disorders. Ellsworth-Howard test remains a
      useful tool in the differential diagnosis of PHP.

PMID- 11297165
TI  - Possible asymptomatic carrier of salmonella typhimurium in the preputium: a case
      report.
AB  - Salmonella infections lead to several clinical syndromes such as acute
      gastroenteritis and bacteremia. Less frequent manifestations are extraintestinal
      focal infections, including urinary tract infections. A 10-month-old boy was
      admitted to the hospital with recurrent urinary tract infections treated with
      antibiotics. Salmonella typhimurium was isolated from the urine samples obtained
      in urine bags. The organism was also grown from a suprapreputial swab, but was
      not grown in the suprapubic urine specimen. Renal ultrasonography, intravenous
      pyelography and voiding cystourethrogram were found normal. The patient was then
      circumcised, following with no uropathogens were isolated from the urine. It is
      believed that circumcision not only prevented further urinary tract infection and
      protected the case from becoming a carrier of Salmonella typhimurium, it also
      halted a possible spread of Salmonella infection to the general public.

PMID- 11297166
TI  - The de Barsy syndrome.
AB  - We report a child with de Barsy syndrome, which is a very rare, genetically
      transmitted clinical entity associated with mental and growth retardation, severe
      cutis laxa, joint laxity and various ocular and skeletal system findings. The
      patient was operated to treat her orthopedic disabilities. Typical findings of
      this case with eight-year follow-up beginning from birth are described and
      compared with previously reported cases. The main aim of this paper was to
      describe the diagnostic and therapeutic difficulties of this rarely encountered
      syndrome.

PMID- 11297167
TI  - Sepsis and multiple brain abscesses caused by Salmonella paratyphi B in an
      infant: successful treatment with sulbactam-ampicillin and surgical drainage.
AB  - Abscess formation by Salmonella species is an uncommon but significant
      manifestation of salmonellosis, because this type of infection has high morbidity
      and mortality rates and is a potential nosocomial hazard. In infants, history of
      consumption of contaminated water should be especially quired. We report a case
      who had sepsis and multiple brain abscesses due to Salmonella paratyphi B and who
      responded to sulbactam-ampicillin (SAM) therapy. Sulbactam-ampicillin combination
      may be preferable due to its immunomodulator effect.

PMID- 11297168
TI  - Chronic inflammatory bowel disease in a patient with common variable
      immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a primary defect of the immune system
      involving an increased risk of respiratory and digestive tract infections and
      autoimmune diseases. Recently, it has been reported that chronic inflammatory
      bowel disease (CIBD) might occur with increased frequency (20%) in patients with
      CVID. A nine-year-old boy with CVID developed CIBD during follow-up and periodic
      intravenous immunoglobulin administration. Serum tumor necrosis factor-a
      concentration, which is suggested to show disease activity in CBD, was very high.
      The patient's radiological evaluation, both in active and remission periods, had
      characteristic features of CBD. We herewith present and discuss this case with
      both diseases, CVID and CIBD.

PMID- 11297169
TI  - Noninvasive diagnosis and surgical management in total anomalous pulmonary venous
      return draining into the coronary sinus: report of 2 cases.
AB  - Total anomalous pulmonary venous return results from nondevelopment of the common
      pulmonary vein, with consequent enlargement of embryonic collaterals between the
      lungs and the systemic veins. In this report, two patients with this anomaly
      draining into the coronary sinus who presented in infancy are described. One of
      the patients was referred because of growth and development failure and chronic
      constipation, while the other had tachypnea as the presenting problem. Both were
      diagnosed during the echocardiographic examination. Typical echocardiographic
      findings were a small left atrium, a sausage-shaped dilated coronary sinus
      receiving the pulmonary veins in the subcostal short axis, and flying seagull
      configuration in the subcostal long axis views. Both had a large interatrial
      communication. The patients underwent corrective surgery. The aim of the
      presentation is to emphasize the role of segmental echocardiography in the
      differential diagnosis.

PMID- 11297170
TI  - Systemic lupus erythematosus presenting with generalized lymphadenopathy: a case
      report.
AB  - Systemic lupus erythematosus (SLE) is an immune complex disease with many
      different clinical presentations. Here we report a 13-year-old female patient
      presenting with generalized lymphadenopathy, who meanwhile developed butterflly
      rash and pericarditis. The diagnosis of SLE was based on the clinical features,
      positive antinuclear antibody, and positive antibodies to dsDNA. The patient had
      an active disease and developed renal involvement, despite steroid therapy. The
      patient's clinical presentation, course and response to therapy are detailed, and
      the literature on lupus lymphadenitis is reviewed.

PMID- 11297171
TI  - Evolution of female remating behaviour following experimental removal of sexual
      selection.
AB  - The relatively small number of ova produced by a female can be fertilized by a
      single ejaculate in most species. Why females of many species mate with multiple
      males is therefore enigmatic, especially given that costs associated with
      remating have been well documented. Recently, it has been argued that females may
      remate at a maladaptive rate as an outcome of sexually antagonistic coevolution:
      the evolutionary tug-of-war between manipulation by one sex and resistance to
      being manipulated by the other sex. We tested this hypothesis experimentally for
      the evolution of the female remating interval in a naturally promiscuous species,
      Drosophila melanogaster. In two replicate populations, sexual selection was
      removed through enforced monogamous mating with random mate assignment, or
      retained in polyandrous controls. Monogamy constrains the reproductive success of
      mates to be identical, thereby converting prior conflicts between mates into
      opportunities for mutualism. Under these experimental conditions, the sexually
      antagonistic coevolution hypothesis generates explicit predictions regarding the
      direction of evolutionary change in female remating behaviour. These predictions
      are contingent upon the mechanism of male manipulation, which may be mediated
      biochemically by seminal fluids or behaviourally by courtship. Levels of
      divergence in female remating interval across lines, and in male ejaculatory and
      courtship effects on female remating, were quantified after 84 generations of
      selection. Data refute the hypothesis that the evolutionary change in female
      remating behaviour was due to sexually antagonistic coevolution of courtship
      signal and receiver traits. The data were, however, consistent with a hypothesis
      of sexual conflict mediated through ejaculate manipulation. Monogamy-line males
      evolved ejaculates that were less effective in inducing female non-receptivity
      and monogamy-line females evolved to remate less frequently, symptomatic of
      lowered resistance to ejaculate manipulation. The consistency of the results with
      alternative hypotheses to explain female promiscuity are discussed.

PMID- 11297172
TI  - Egg colour matching in an African cuckoo, as revealed by ultraviolet-visible
      reflectance spectrophotometry.
AB  - Despite major differences between human and avian colour vision, previous studies
      of cuckoo egg mimicry have used human colour vision (or standards based thereon)
      to assess colour matching. Using ultraviolet-visible reflectance
      spectrophotometry (300-700 nm), we measured museum collections of eggs of the red
      chested cuckoo and its hosts. The first three principal components explained more
      than 99% of the variance in spectra, and measures of cuckoo host egg similarity
      derived from these transformations were compared with measures of cuckoo host egg
      similarity estimated by human observers unaware of the hypotheses we were
      testing. Monte Carlo methods were used to simulate laying of cuckoo eggs at
      random in nests. Results showed that host and cuckoo eggs were very highly
      matched for an ultraviolet versus greenness component, which was not detected by
      humans. Furthermore, whereas cuckoo and host were dissimilar in achromatic
      brightness, humans did not detect this difference. Our study thus reveals aspects
      of cuckoo-host egg colour matching which have hitherto not been described. These
      results suggest subtleties and complexities in the evolution of host-cuckoo egg
      mimicry that were not previously suspected. Our results also have the potential
      to explain the longstanding paradox that some host species accept cuckoo eggs
      that are non-mimetic to the human eye.

PMID- 11297173
TI  - Trends in the maternal investment of harbour porpoises are uncoupled from the
      dynamics of their primary prey.
AB  - Harbour porpoises in the Bay of Fundy and Gulf of Maine feed primarily on
      Atlantic herring. Herring stocks have undergone dramatic fluctuations in
      abundance over the past three decades due to changes in fishing intensity. In
      order to understand the effects of these changes in prey abundance on the
      patterns of maternal investment, I examined interdecadal variation in the size of
      porpoise calves measured in August prior to weaning. Female harbour porpoises
      exhibited significant variation in maternal investment between 1970 and 1999.
      During the 1980s, females consumed more herring and produced larger calves.
      Surprisingly, however, this increased maternal investment occurred during the
      period of lowest prey abundance, perhaps because the herring stock assessment
      does not reflect the availability or quality of prey to female porpoises.

PMID- 11297174
TI  - Coexistence induced by pollen limitation in flowering-plant species.
AB  - We report a novel mechanism for species coexistence that does not invoke a trade
      off relationship in the case of outbreeding flowering plants. Competition for
      pollination services may lead to interspecific segregation of the timing of
      flowering among plants. This, in turn, sets limits on the pollination services,
      which restrain the population growth of a competitively superior species, thereby
      allowing an inferior species to sustain its population in the habitat. This
      explains the often-observed tendency for interspecific differentiation in the
      timing of flowering between coexisting plants. It also predicts that the
      introduction of an efficient pollinator to a habitat may cause the extinction of
      competitively inferior plant species.

PMID- 11297175
TI  - The flock-to-flock force of infection for scrapie in Britain.
AB  - A postal survey of British sheep farmers provided information on the proportion
      of farms that experienced their first case of scrapie in each year between 1962
      and 1998. We found no evidence of a large increase in the proportion of scrapie
      affected farms prior to, during or following the epidemic of BSE in British
      cattle. After correcting for between-farm heterogeneity in the probability of
      acquiring scrapie, we estimated the yearly between-flock force of infection since
      1962. The current force of infection is estimated at approximately 0.0045 per
      farm per year and combined with a simple model of scrapie spread provides an
      estimate of the average duration of a scrapie outbreak on an individual farm.
      Considering all farms, the average outbreak lasts for five years, but if only
      those farms that have cases in animals born on the farm are considered, it lasts
      15 years. We use these parameter estimates to compare the proportion of farms
      with scrapie in time periods of different lengths. In the survey, 2.7% of farms
      had a case in 1998. The 5.3% of farms reporting having a case between 1993 and
      1997 is consistent with the hypothesis that the scrapie force of infection
      remained constant over this period.

PMID- 11297176
TI  - Detection of palm fruit lipids in archaeological pottery from Qasr Ibrim,
      Egyptian Nubia.
AB  - In modern times, the trees of the palm family have been of great economic and
      social importance to the people in Egypt, as in other parts of the world. There
      are various species of palm and although different parts of the tree can be used,
      the fruit are of great value. In antiquity, it is expected that the palm fruit
      would also have been of great importance to people in the region. The chemical
      analysis of absorbed residues in archaeological pottery is well established, and
      through the investigation of ceramic vessels (via gas chromatography, gas
      chromatography-mass spectrometry and gas chromatography-combustion-isotope ratio
      mass spectrometry) saturated carboxylic acids in the range C12 to C18 have been
      detected (with an unusually high abundance of C12) from vessels from the Nubian
      site of Qasr Ibrim. This is mirrored in the saturated fatty acid distributions
      detected from the kernels of modern and ancient date palm (Phoenix dactylifera
      L.) and dom palm (Hyphaena thebaica (L.) Mart.). Mixing in some of the vessels of
      the palm fruit with another lipid source is indicated through the delta13C
      values. These results provide the first direct evidence for the exploitation of
      palm fruit in antiquity and the use of pottery vessels in its processing.

PMID- 11297177
TI  - A three-dimensional model for ciliary motion based on the internal 9+2 structure.
AB  - Here we present, to our knowledge, the first modelling platform that enables
      simulations of three-dimensional (3D) motion of multicilia arrays at a detailed
      level. It consists of three building blocks: (i) geometric equations for tracking
      the 3D motion of the cilia, (ii) a hydrodynamic description of the ciliary
      system, and (iii) model equations for the internal bend generating based on the 9
      + 2 structure. The model generates seemingly realistic 3D beat patterns and
      demonstrates metachronal coordination that evolves autonomously as a result of
      the hydrodynamic coupling between the cilia. We study the effect of the twisting
      motion within the cilia and propose a conjecture on a possible role of the radial
      spokes system.

PMID- 11297178
TI  - Population genetic structure and vocal dialects in an amazon parrot.
AB  - The relationship between cultural and genetic evolution was examined in the
      yellow-naped amazon Amazona auropalliata. This species has previously been shown
      to have regional dialects defined by large shifts in the acoustic structure of
      its learned contact call. Mitochondrial DNA sequence variation from a 680 base
      pair segment of the first domain of the control region was assayed in 41 samples
      collected from two neighbouring dialects in Costa Rica. The relationship of
      genetic variation to vocal variation was examined using haplotype analysis,
      genetic distance analysis, a maximum-likelihood estimator of migration rates and
      phylogenetic reconstructions. All analyses indicated a high degree of gene flow
      and, thus, individual dispersal across dialect boundaries. Calls sampled from
      sound libraries suggested that temporally stable contact call dialects occur
      throughout the range of the yellow-naped amazon, while the presence of similar
      dialects in the sister species Amazona ochrocephala suggests that the propensity
      to form dialects is ancestral in this clade. These results indicate that genes
      and culture are not closely associated in the yellow-naped amazon. Rather, they
      suggest that regional diversity in vocalizations is maintained by selective
      pressures that promote social learning and allow individual repertoires to
      conform to local call types.

PMID- 11297179
TI  - Selfish element maintains sex in natural populations of a parasitoid wasp.
AB  - Genomic conflicts between heritable elements with different modes of inheritance
      are important in the maintenance of sex and in the evolution of sex ratio.
      Generally, we expect sexual populations to exhibit a 1:1 sex ratio. However,
      because of their biology, parasitoid wasps often exhibit a female-biased sex
      ratio. Sex-ratio distorters can further alter this optimum, sometimes leading to
      the complete loss of sexual reproduction. In the parasitoid wasp Trichogramma
      kaykai ca. 4-26% of females in field populations are infected with a bacterial
      sex-ratio distorter, Wolbachia, allowing virgin mothers to produce daughters. In
      some micro-Hymenoptera these infections have led to the complete loss of sex, but
      in field populations of T. kaykai the proportion of individuals infected remains
      relatively stable. We tested several hypotheses to explain this low infection
      level, including inefficient and horizontal transmission of Wolbachia, suppressor
      genes negating the effect of Wolbachia and the presence of male-biasing sex-ratio
      distorters. Here, a male-biasing sex-ratio distorter, a parasitic B chromosome,
      causing females to produce only sons, keeps the frequency of Wolbachia low. The
      male-biasing factor of T. kaykai is the second known case of a B chromosome
      manipulating the reproduction of a parasitoid wasp.

PMID- 11297180
TI  - The mitochondrial genomes of the iguana (Iguana iguana) and the caiman (Caiman
      crocodylus): implications for amniote phylogeny.
AB  - The complete mitochondrial genomes of two reptiles, the common iguana (Iguana
      iguana) and the caiman (Caiman crocodylus), were sequenced in order to
      investigate phylogenetic questions of tetrapod evolution. The addition of the two
      species allows analysis of reptilian relationships using data sets other than
      those including only fast-evolving species. The crocodilian mitochondrial genomes
      seem to have evolved generally at a higher rate than those of other vertebrates.
      Phylogenetic analyses of 2889 amino-acid sites from 35 mitochondrial genomes
      supported the bird-crocodile relationship, lending no support to the
      Haematotherma hypothesis (with birds and mammals representing sister groups). The
      analyses corroborated the view that turtles are at the base of the bird-crocodile
      branch. This position of the turtles makes Diapsida paraphyletic. The origin of
      the squamates was estimated at 294 million years (Myr) ago and that of the
      turtles at 278 Myr ago. Phylogenetic analysis of mammalian relationships using
      the additional outgroups corroborated the Marsupionta hypothesis, which joins the
      monotremes and the marsupials to the exclusion of the eutherians.

PMID- 11297181
TI  - Loss of preferred mates forces female satin bowerbirds (Ptilonorhynchus
      violaceus) to increase mate searching.
AB  - Variation in mate choice among females can have important consequences for the
      operation of sexual selection, and can result from differences in the way females
      search for mates. Our previous work indicates that female satin bowerbirds
      Ptilonorhynchus violaceus alter their mate-searching patterns according to long
      term experience. Females which mate with very attractive males mate with the same
      males in the following year, thereby reducing their search. In contrast, females
      which fail to encounter very attractive males typically reject their previous
      mates and search for more attractive males in the following year, thereby
      increasing their search. Here we report results from a natural experiment
      consistent with these observations. Five males, including the most attractive
      male of 1997, failed to re-establish display sites in 1998, most probably dying
      over winter. We monitored the mate-searching behaviour of females which mated
      with these males in 1997 to determine how the loss of attractive mates affects
      subsequent mate-searching patterns. Females which lost their mates sampled more
      males compared with their own search patterns in 1997 and with faithful females
      in 1998. Results from this natural experiment indicate that the loss of
      attractive and preferred mates forces females to increase their search and
      provide evidence that long-term experience with males shapes mate-searching
      behaviour.

PMID- 11297182
TI  - Asymmetrical expression of transsexual phenotypes in hummingbirds.
AB  - I present evidence for asymmetry in the expression of transsexual traits in adult
      hummingbirds. Among females, individuals with male-like plumage are common and
      define a continuous range of variation. Among males, individuals with female-like
      plumage are rare and define discontinuous plumage morphs. Quantitative characters
      also distinguish transsexuals from other members of their sex, but the characters
      involved differ for male-like females (bill length) and female-like males (bill,
      wing and tail length). Gonadal development is correlated with transsexuality only
      in males; female-like males have significantly smaller testes than male-like
      males. Both sexes demonstrate a significant negative association between plumage
      brightness and bill length. This association suggests an ecological basis for
      transsexuality because differences in plumage and bill morphology are associated
      with differences in foraging behaviour within and between hummingbird species.
      Morphological differences between transsexuals and non-transsexuals imply that
      plumage sexual dimorphism is more likely to evolve through changes in the
      frequency of female, rather than male, transsexual variants.

PMID- 11297183
TI  - Induced maternal response to the Lyme disease spirochaete Borrelia burgdorferi
      sensu lato in a colonial seabird, the kittiwake Rissa tridactyla.
AB  - Mothers are predicted to invest in their offspring depending on the quality of
      their mate, their opportunity to invest in future reproduction and the
      characteristics of the habitat in which their offspring will be born. Recent
      studies have suggested a transfer of maternal immunity to offspring as an induced
      response to the local presence of parasites in the environment, but evidence has
      been indirect. Here, we show the presence of antibodies against the Lyme disease
      agent Borrelia burgdorferi sensu lato, a spirochaete transmitted by the seabird
      tick Ixodes uriae, in the eggs of kittiwakes Rissa tridactyla. We report higher
      prevalence of antibodies against Borrelia in eggs from breeding areas with higher
      prevalence and abundance of ticks. Further, high repeatabilities of antibody
      positive eggs within clutches and between first and replacement clutches show
      that, within a breeding season, females differ consistently with respect to the
      expression of this induced maternal response. Our results suggest that mothers
      can alter investment in their young depending on local conditions. Such maternal
      effects clearly have implications for the ecology and evolution of host-parasite
      interactions.

PMID- 11297184
TI  - Pollination and parasitism in functionally dioecious figs.
AB  - Fig wasps (Agaonidae: Hymenoptera) are seed predators and their interactions with
      Ficus species (Moraceae) range from mutualism to parasitism. Recently
      considerable attention has been paid to conflicts of interest between the
      mutualists and how they are resolved in monoecious fig species. However, despite
      the fact that different conflicts can arise, little is known about the factors
      that influence the persistence of the mutualism in functionally dioecious Ficus.
      We studied the fig pollinator mutualism in 14 functionally dioecious fig species
      and one monoecious species from tropical lowland rainforests near Madang, Papua
      New Guinea. Observations and experiments suggest that (i) pollinating wasps are
      monophagous and attracted to a particular host species; (ii) pollinating and non
      pollinating wasps are equally attracted to gall (male) figs and seed (female)
      figs in functionally dioecious species; (iii) differing style lengths between
      gall figs and seed figs may explain why pollinators do not develop in the latter;
      (iv) negative density dependence may stabilize the interaction between
      pollinating wasps and their parasitoids; and (v) seed figs may reduce the search
      efficiency of non-pollinators. This increased pollinator production without a
      corresponding decrease in seed production could provide an advantage for dioecy
      in conditions where pollinators are limiting.

PMID- 11297185
TI  - Optimal allocation of reproductive effort: manipulation of offspring number and
      size in the bank vole.
AB  - The number of offspring attaining reproductive age is an important measure of an
      individual's fitness. However, reproductive success is generally constrained by a
      trade-off between offspring number and quality. We conducted a factorial
      experiment in order to study the effects of an artificial enlargement of
      offspring number and size on the reproductive success of female bank voles
      (Clethrionomys glareolus). We also studied the effects of the manipulations on
      growth, survival and reproductive success of the offspring. Potentially
      confounding effects of varying maternal quality were avoided by cross-fostering.
      Our results showed that the number of offspring alive in the next breeding season
      was higher in offspring number manipulation groups, despite their smaller body
      size at weaning. Offspring size manipulation had no effect on offspring growth or
      survival. Further, the first litter size of female offspring did not differ
      between treatments. In conclusion, females may be able to increase the number of
      offspring reaching reproductive age by producing larger litters, whereas
      increasing offspring size benefits neither the mother nor the offspring.

PMID- 11297186
TI  - Provider distribution and variations in statewide cesarean section rates.
AB  - Cesarean section rates vary among states from approximately 15% to over 26% of
      all deliveries. Since it is unlikely that patient factors alone contribute to
      this wide variation, other non-clinical factors that are unique to each state
      must influence cesarean section decisions. To explore if provider workforce and
      specialty was associated with differences in statewide cesarean rates, we
      compared statewide cesarean rates for 1996 with (1) the volume of deliveries in a
      state per board-certified obstetrician; (2) percentage of deliveries performed in
      the state by nurse midwives, and (3) the percentage of family physicians in the
      state performing obstetrics. In a linear regression model that adjusted for state
      rurality and median income, we found that only the percentage of family
      physicians participating in obstetrics was related to cesarean delivery rates. As
      the percentage of family physicians offering obstetric services increased in a
      state, the rate of cesarean delivery for that state declined. This effect
      appeared to be independent of other provider effects, state rurality, or
      statewide income. Family physician participation in obstetrics is unlikely to be
      the cause for lower cesarean rates, but is likely a marker for a medical
      environment and practice style that supports non-operative obstetric care.

PMID- 11297187
TI  - Psychiatrists' knowledge and attitudes about costs of commonly prescribed
      treatments in psychiatry.
AB  - A survey was conducted to assess psychiatrists' knowledge and attitudes regarding
      the costs of various psychiatric treatments. Psychiatrists (n = 500) were
      randomly selected from the membership of the Ohio Psychiatric Association. The
      survey explored several aspects of psychiatrists' knowledge of costs, including
      estimated prices of 24 specific psychiatric treatments (frequently used
      psychotropic medications, laboratory tests, and inpatient and outpatient
      procedures) as well as their level of confidence in their estimates. The survey
      also asked a series of attitude/opinion questions and specific demographic data.
      The psychiatrists (n = 265, 59% response) perceived that knowing the costs of
      treatments was an important consideration when choosing a particular treatment.
      Psychiatrists' actual knowledge of the costs of treatment was inconsistent with
      their beliefs of the importance of knowing the costs as well as their reported
      confidence in their knowledge of costs. Information about the costs of
      psychiatric treatments is an important clinical consideration and a program to
      improve clinicians' knowledge of the costs of psychiatric treatment could occur
      during residency training.

PMID- 11297188
TI  - Workplace tobacco policy: progress on a winding road.
AB  - This is a report of a pre- and post-intervention telephone survey to track
      changes in workplace tobacco policy in Pima County, Arizona, from 1997 to 1999.
      During this period, an extensive effort was made to assist workplaces to
      establish and enforce formal tobacco use policies. A random sample of 1134
      workplaces, stratified by workforce size, was surveyed in 1997. Complete
      interviews were conducted with 934 (82.4%) workplaces. All 934 workplaces were
      contacted for the follow-up survey that was conducted in 1999. Of these, 824
      (88.2%) completed follow-up surveys. The analyses presented were conducted on
      businesses that were included in both the baseline and follow-up surveys, and
      that reported having at least one employee on-site (n = 813). Tobacco policies
      and smoke-free policies were more likely to be found in larger businesses and
      businesses with a predominantly female workforce. There was no clear policy
      progression from having no policy, to having a policy, to becoming smoke-free.
      There was a small but significant overall decrease (4.8%) in the proportion of
      businesses having policies in the last two years. We found that 10.3% (75) of
      businesses that had policies in 1997 had dropped their policies by 1999, and that
      13.4% (73) of worksites that were smoke-free in 1997 retained tobacco policies
      but were not smoke-free in 1999. However, formalization of policy in writing and
      the number of enforcement strategies utilized increased. These findings suggest
      that efforts to encourage businesses to establish workplace tobacco policies must
      be sustained even after policies have been established.

PMID- 11297189
TI  - Disparities in hormone replacement therapy use by socioeconomic status in a
      primary care population.
AB  - The use of hormone replacement therapy (HRT) is a controversial decision for many
      women, yet few studies have evaluated the socio-demographic, psychological, and
      behavioral correlates of HRT use. This cross-sectional, mailed survey evaluated
      the associations of socioeconomic status, preventive health behaviors, knowledge
      and perceptions about HRT-related risks and benefits with HRT use among 428 women
      50-70 years old in Vermont. The overall prevalence of HRT use was 40%. Women of
      moderate to high income were three times more likely than those of low income to
      use HRT. HRT use was significantly higher among women whose physician had
      encouraged use (58%) than among those who received ambivalent recommendations
      from their physicians (20%). Hysterectomy, higher income, younger age, regular
      adherence to cervical cancer screening, and recommendation by a provider were
      significantly associated with HRT use in multivariate analyses. There were no
      differences in HRT use according to level of concern about heart disease,
      osteoporosis, or breast cancer. A recommendation by a health care provider is a
      powerful predictor of HRT use, but disparities in use exist by socioeconomic
      status. Future research should examine why lower income women are less likely to
      use HRT and whether the discrepancy is due to inconsistent recommendations by
      health care providers.

PMID- 11297190
TI  - Village-based primary health care in the Central Highlands of Vietnam.
AB  - This paper describes the first year of an ongoing village health care and
      economic development project in the Krong Buk district of Dak Lak province in
      Vietnam's Central Highlands. The project serves 21 villages with a total
      population of just over 15,000. Most belong to ethnic minority groups. Physicians
      from the province capital of Boun Me Thuot were trained by a multi-disciplinary
      team of American health care workers to be trainers and supervisors of 21 village
      health care workers (VHWs). Two months later, a VHW from each village was trained
      in primary and preventive health care by the physician-supervisors. Since this
      initial training, each VHW has been provided with materials, medicines and
      monthly supervision by the physician-supervisors. The health care component has
      been complemented by an economic development project based on a system of small
      loans. Data from the first year of monthly reports and from a baseline survey are
      presented in this paper.

PMID- 11297191
TI  - Biochemistry and physiology of anabolic hormones used for improvement of meat
      production.
AB  - A number of hormones are involved in endocrine regulation of growth. In general,
      these hormones enhance body protein accretion and metabolise fat stores resulting
      in increased lean growth rates. Most practical importance was obtained by sex
      hormones (oestrogens and androgens), beta-agonists and growth hormone - whether
      legally or illegally. Efficiency of growth promotion ranges between 0% and +20%
      depending on the prerequisites such as species, breed, gender, age, reproductive
      status, body score or feeding of the animals. Oestrogens and androgens mediate
      their activity via intracellular receptors - directly in muscular tissue as well
      as indirectly via stimulation of growth hormone from the hypophysis and other
      growth factors from liver plus several further organs. In addition, mineral
      absorption in the gut is improved. The outstanding efficiency of trenbolone is
      based on its androgenic plus antiglucocorticoid activity. Melengestrolacetate is
      thought to act indirectly via stimulation of endogenous ovarian oestradiol in non
      pregnant heifers. The necessary dosages and residue formations depend on the
      pharmacokinetic parameters of each substance and extrapolations between compounds
      are hardly possible. Growth hormone and beta2-agonists use independent pathways
      for growth promotion not related to steroid biochemistry.

PMID- 11297192
TI  - Assessment of estradiol and its metabolites in meat.
AB  - Most studies related to research on steroids in main edible tissues (muscle,
      liver or kidney) have focused on measurement of parent or major metabolite
      residues. In order to evaluate the estradiol content in bovine edible tissues, a
      multi-step extraction procedure was developed in conjunction with parallel
      metabolism studies of [14C]-17beta-estradiol in cattle (1-2). Various classes of
      free estradiol and conjugates were separated: estradiol -17beta and -17alpha,
      estradiol-17-fatty acid esters, estradiol 17-glycoside, estradiol 3-glucuronide,
      estradiol-17-glycoside and 3- glucuronide (diconjugates) were separated. No
      sulphates conjugated forms have been found at the detection level of the method.
      The quantification was realized by calibration with deuterated 17beta -estradiol 
      d3 standard and was validated at the ng x kg(-1) (ppt) level. Muscle, liver,
      kidney and fat samples from control or Revalor S single (licensed implantation)
      or multi-implanted steers have been assayed. The results show a wide variation
      between animals, but both the highest value and the mean of total estradiol
      content in each group proportionally increase from untreated to multi-implanted
      animals. In accordance with international rules, a calculation of the daily food
      supply of estradiol by such edible tissues in comparison with the acceptable
      daily intake was performed.

PMID- 11297193
TI  - Carcinogenicity of estrogens in human breast epithelial cells.
AB  - Epidemiological and clinical evidences indicate that breast cancer risk is
      associated with prolonged ovarian function that results in elevated circulating
      levels of steroid hormones. Principal among these is estrogen, which is
      associated with two important risk factors, early onset of menarche and late
      menopause. However, up to now there is no direct experimental evidence that
      estrogens are responsible of the initiation of human breast cancer. We postulate
      that if estrogens are causative agents of this disease, they should elicit in
      human breast epithelial cells (HBEC) genomic alterations similar to those
      exhibited by human breast cancers, such as DNA amplification and loss of genetic
      material representing tumor suppressor genes. These effects could result from
      binding of the hormone to its nuclear receptors (ER) or from its metabolic
      activation to reactive metabolites. This hypothesis was tested by treating with
      the natural estrogen 17beta-estradiol (E2) and the synthetic steroid
      diethylstilbestrol (DES) MCF-10F cells, a HBEC line that is negative for ER.
      Cells treated with the chemical carcinogen benzo (a) pyrene (BP) served as a
      positive control of cell transformation. BP-, E2-, and DES-treated MCF-10F cells
      showed increases in survival efficiency and colony efficiency in agar methocel,
      and loss of ductulogenic capacity in collagen gel. The largest colonies were
      formed by BP-treated cells, becoming progressively smaller in DES- and E2-treated
      cells. The loss of ductulogenic capacity was maximal in BP-, and less prominent
      in E2- and DES-treated cells. Genomic analysis revealed that E2- and DES-treated
      cells exhibited loss of heterozygosity in chromosomes 3 and 11, at 3p21, 3p21
      21.2, 3p21.1-14.2, and 3p14.2 14.1, and at 11q23.3 and 11q23.1-25 regions,
      respectively. It is noteworthy that these loci are also affected in breast
      lesions, such as ductal hyperplasia, carcinoma in situ, and invasive carcinoma.
      Our data are the first ones to demonstrate that estrogens induce in HBEC
      phenotypic changes indicative of cell transformation and that those changes are
      associated with significant genomic alterations that might unravel new pathways
      in the initiation of breast cancer.

PMID- 11297194
TI  - Hormone contents in peripheral tissues after correct and off-label use of growth
      promoting hormones in cattle: effect of the implant preparations Filaplix-H,
      Raglo, Synovex-H and Synovex Plus.
AB  - Certain hormonal growth promoters are licensed in several beef producing
      countries outside the European Union (EU). Use in compliance with Good Veterinary
      Practice is mandatory. As risk assessment of hormone residues in animal tissues
      up to now has neglected potential off-label use, the present study dealt with two
      topics: 1) multiple treatment with the implant preparations Finaplix-H (200 mg
      trenbolone acetate), Ralgro (36 mg zeranol) and Synovex-H (200 mg testosterone
      propionate plus 20 mg estradiol benzoate) in heifers (1-fold, 3-fold and 10-fold
      dose), and 2) non-approved treatment of female veal calves (1-fold dose of
      Synovex-H or Synovex Plus with 200 mg trenbolone acetate plus 28 mg estradiol
      benzoate). Residues of estradiol-17beta, estradiol-17alpha, estrone and
      testosterone, trenbolone-17beta, trenbolone-17alpha and trendione or zeranol,
      respectively, were measured in loin, liver, kidney and peri-renal fat by high
      performance liquid chromatography/enzyme immunoassay (HPLC/EIA) after liquid
      liquid extraction and solid-phase clean-up. The hormone residues in the multiple
      dose experiments were dose-dependent and partially exceeded the threshold values:
      in the liver in one animal after 3-fold dose and in two animals after 10-fold
      dose of Finaplix-H, and in the liver and kidney after 3-fold and 10-fold dose of
      Synovex-H. Mean hormone residues in calves were mainly below those of heifers and
      did not infringe threshold values.

PMID- 11297195
TI  - Intratumoral microvascular density in malignant lymphomas of B-cell origin.
AB  - Sections of surgical lymph-node biopsies of four types of malignant non-Hodgkin's
      lymphoma of B-cell origin (B-NHL) classified according to the R.E.A.L.
      terminology or lymphadenitis were immunostained in order to demonstrate
      endothelial CD34 (QBEnd 10) and to determine the microvascular density and vessel
      size distribution using an interactive image-analysis technique. Only
      microvessels displaying a cross-sectional area corresponding to a diameter of
      between 3.2 and 34.6 microm were included. The intratumoral microvascular density
      (iMVD) was found to be significantly higher in chronic lymphatic leukaemia (CLL,
      n = 13) compared with the clinically more aggressive mantle cell lymphoma (MCL, n
      = 9) and diffuse large B-cell lymphoma (DLBCL, n = 14). iMVD in CLL was also
      higher than in the follicular neoplastic parts (FL FOLL) of follicular lymphoma
      (FL, n = 16). In FL FOLL the microvessel density was, moreover, significantly
      lower than in the surrounding non-neoplastic FL tissue. In lymphadenitis (LA, n =
      10) the iMVD was higher than in DLBCL, FL FOLL and MCL. The data suggest that
      future studies focusing on the relationship between iMVD and the clinical outcome
      within each particular NHL group should be carried out in order to verify whether
      iMVD is a prognostic factor in NHL, as it is in carcinomas.

PMID- 11297196
TI  - Detection of mRNA for the terminal complement components C5, C6, C8 and C9 in
      human umbilical vein endothelial cells in vitro.
AB  - Human umbilical vein endothelial cells (HUVEC) have previously been shown to
      synthesize the functional terminal pathway of complement based on the detection
      by radioimmunoassay of the terminal complement complex (TCC) on coincubated
      agarose beads. In addition, C7 secretion by these cells in amounts comparable to
      C3, as well as C7 mRNA, has recently been demonstrated. However, it has not been
      possible to detect C5-6 and C8 in the fluid phase, and only trace amounts of
      soluble C9. Against this background we examined whether mRNA for the remaining
      terminal complement factors was present in HUVEC. By the use of reverse
      transcription (RT)-polymerase chain reaction (PCR) and Northern blot the presence
      of mRNA for complement factors C5, C6, C8 and C9 was demonstrated.

PMID- 11297197
TI  - ABH and Lewis histo-blood group antigens in cancer.
AB  - Antigens of the ABH and Lewis histo-blood group family can be found on many
      normal cells, mainly of epithelial type. In carcinomas, altered expression of the
      various carbohydrate epitopes of this family occur, and are often strongly
      associated with either a good or bad prognosis. A review of the available data on
      these tumor-associated markers, their biosynthesis and their prognostic value is
      proposed here. For a long time it has been unclear whether their presence could
      affect the behavior of carcinoma cells. Recent data, however, indicate that they
      play biological roles in the course of tumor progression. The presence of sialyl
      Le(a) or sialyl-Le(x), which are ligands for selectins, promotes the metastatic
      process by facilitating interaction with the endothelium of distant organs. The
      loss of A and B antigens increases cellular motility, while the presence of H
      epitopes increases resistance to apoptosis by mechanisms that remain to be
      defined. The Le(y) antigen has procoagulant and angiogenic activities. All these
      observations are used to present a model that may account for the described
      associations between the presence or loss of these markers and the outcome of
      disease. Finally, their potential clinical applications as tumor-associated
      markers or as targets of immunotherapy are reviewed.

PMID- 11297198
TI  - Echocardiographic assessment of the normal mitral annular size.

PMID- 11297199
TI  - Major and minor axes of the normal mitral annulus.
AB  - BACKGROUND AND AIM OF THE STUDY: A dilated or abnormally shaped mitral annulus is
      a common cause of mitral valve regurgitation, and may be cured by annuloplastic
      surgery. Multiplane transesophageal echocardiography (TEE) is the diagnostic
      technique of choice. Our aim was to evaluate and suggest two-dimensional TEE
      reference values from a standardized procedure of measuring the mitral annular
      major and minor axes, and their cyclic changes. METHODS: The annulus was
      approximated elliptic in the horizontal plane. The intercommissural (IC, major
      axis) and anteroposterior (AP, minor axis) distances were measured at end-systole
      (ES), at maximal valve opening (MO), and at end-diastole (ED) from a mid
      esophageal view, in 13 men and eight women with normal echocardiographic
      findings. Indexed values and reproducibility were calculated. RESULTS: The
      success rate was 100% at ES, 90% at MO, and 29% at ED. ES distances were largest
      (p <0.001) and most reproducible (5-5.9%). Body weight, but not height or age,
      had a significant impact. ES 95% prediction intervals for IC were 27 to 46 mm (16
      23 mm/m2) and 22 to 36 mm (13-18 mm/m2) for AP (p <0.001). Corresponding body
      weight-corrected intervals were 0.39 to 0.59 (IC) and 0.32 to 0.48 (AP) mm/kg. No
      subject had IC:AP <1.1 together with an AP >0.45 mm/kg. CONCLUSION: Among
      measurements made at ES, MO and ED, those at ES provided the most reproducible
      results, and high-quality images were obtained in normal, non-obese subjects. The
      distances should be judged in relation to body weight or surface area and each
      other. The largest IC distance and the most elliptic shape were at ES, while the
      annulus was minimal at ED. The procedure and normal ranges presented may
      contribute to the evaluation of patients with mitral regurgitation.

PMID- 11297200
TI  - Long-Term outcome of mitral balloon valvotomy in pregnant women.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to examine the long-term
      outcome (nine years) of mitral balloon valvotomy in pregnant patients with severe
      mitral stenosis. METHODS: Twenty-three patients with severe, symptomatic (NYHA
      class III/IV) mitral stenosis underwent mitral balloon valvotomy using an Inoue
      balloon technique during the second trimester of their pregnancy; mean follow up
      in 19 patients was 5.1 +/- 2.8 years (range: 1 to 9 years). RESULTS: The
      procedure was successful in all patients. Immediately after valvotomy, the
      Doppler-derived mitral valve area increased from 0.90 +/- 0.18 to 1.97 +/- 0.36
      cm2 (p <0.0001), and the transmitral mean gradient decreased from 15.7 +/- 4.7 to
      5.5 +/- 1.6 mmHg (p <0.0001). Four patients had mild worsening of mitral
      regurgitation, and six developed insignificant interatrial communication
      immediately after valvotomy. There was no other morbidity or mortality. Patients
      showed a significant improvement in mean NYHA class, from 3.0 +/- 0.1 to 1.0 +/-
      0.02 (p <0.001). Twenty-two patients had normal deliveries; one cesarean section
      in week 36 resulted in stillbirth. No developmental abnormalities were seen in
      the babies. At long-term follow up of mothers, the mitral valve area was 1.8 +/-
      0.52 cm2; restenosis developed in three patients (16%). One baby died at one week
      from sudden infant death syndrome, and one at eight months, from pneumonia. All
      other children showed normal growth, development and speech for their age.
      CONCLUSION: Mitral balloon valvotomy using the Inoue balloon technique can
      provide satisfactory immediate relief and long-term outcome in pregnant patients
      with severe mitral stenosis.

PMID- 11297201
TI  - Beneficial effects of nicorandil versus enalapril in chronic rheumatic severe
      mitral regurgitation: six months follow up echocardiographic study.
AB  - BACKGROUND AND AIM OF THE STUDY: It is possible that vasodilator therapy may
      retard left ventricular (LV) dilatation and functional deterioration in chronic
      mitral regurgitation (MR). The study objectives were to evaluate comparatively
      the efficacy of nicorandil (a new, balanced vasodilator) and enalapril therapy on
      LV volume, mass and function in mildly symptomatic, chronic rheumatic severe MR.
      METHODS: Eighty-seven mildly symptomatic rheumatic patients with severe MR were
      enrolled in this prospective, randomized study. All patients underwent serial
      echocardiography study at entry, and again at six months. Eighty patients
      completed the study. RESULTS: At six months, the nicorandil and enalapril patient
      groups each had a significant reduction in LV end-systolic volume index (57.4 +/-
      24.8 versus 43.2 +/- 20.7 ml/m2, p = 0.003; 50.0 +/- 19.0 versus 40.4 +/- 14.2
      ml/m2, p = 0.006, respectively) and LV mass index (218.0 +/- 88.0 versus 188.0 +/
      76.0 g/m2, p = 0.05; 217.2 +/- 48.0 versus 186.2 +/- 45.0 g/m2, p = 0.002
      respectively). Both nicorandil and enalapril caused significant improvement in
      ejection fraction (63.8 +/- 7.0 versus 71.0 +/- 6.7%, p <0.0001; 63.2 +/- 6.9
      versus 67.5 +/- 6.4%, p = 0.002, respectively) and a reduction in LV end-systolic
      stress (152.9 +/- 29.0 versus 126.0 +/- 25.0 dyne/cm2, p = 0.001; 150.0 +/- 30.2
      versus 138.0 +/- 29.0 dyne/cm2, p = 0.002, respectively). However, nicorandil
      caused a greater reduction in absolute LV end-systolic volume index (13.3 +/-
      10.1 versus 9.6 +/- 5.9 ml/m2, p = 0.02), and a greater improvement in absolute
      ejection fraction (7.2 +/- 4.7 versus 4.2 +/- 2.6%, p = 0.0005) than enalapril.
      CONCLUSION: It is concluded that nicorandil is equivalent to enalapril in
      improving LV volume, mass, end-systolic stress and ejection fraction in mildly
      symptomatic chronic rheumatic severe mitral regurgitation over a period of six
      months.

PMID- 11297202
TI  - Hemodynamics of semilunar valves at rest and exercise at an average of more than
      two years after the Ross procedure.
AB  - BACKGROUND AND AIM OF THE STUDY: Rest, and especially exercise, hemodynamics are
      valuable determinants to assess outcome of the Ross procedure. In this study, the
      degree of insufficiency and pressure gradients at rest across the autograft and
      homograft, as well as the pressure gradients at exercise, were measured. METHODS:
      Among 115 patients operated on between February 1990 and February 1999, 67 were
      evaluated echocardiographically at rest and moderate exercise. The mean patient
      age at subcoronary implantation was 52 +/- 13 years. The mean interval between
      surgery and investigation was 27.3 +/- 17.4 months. The exercise level was 100 W
      (n = 47), 75 W (n = 14) or 50 W (n = 6). RESULTS: Fifty-two patients had no or
      trace aortic insufficiency, 23 were grade I/IV, and two were grade II/IV.
      Pulmonary insufficiency was graded as none (n = 45), mild (n = 21), and moderate
      (n = 1). Heart rate increased from 70 +/- 12 beats/min at rest to 108 +/- 19
      beats/min at exercise. The maximal pressure gradient across the autograft
      increased from 6.1 +/- 2.3 mmHg at rest to 8.7 +/- 4.1 mmHg at exercise. The
      maximal pressure gradient across the homograft increased from 11.8 +/- 5.3 mmHg
      at rest to 17.7 +/- 8.2 mmHg at exercise. A pressure gradient across the
      homograft >25 mmHg was measured in 13 patients. CONCLUSION: In most patients,
      hemodynamics at rest and moderate exercise at an average of more than two years
      after the Ross procedure were excellent. Some homografts developed pressure
      gradients at exercise; this finding will form the target of future surgical and
      scientific investigations.

PMID- 11297203
TI  - Echocardiographic assessment and preliminary clinical results after aortic valve
      replacement with the Medtronic Mosaic bioprosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to examine prospectively the
      clinical performance and durability of the Medtronic Mosaic bioprosthesis, a
      stented porcine aortic valve that combines improvements in tissue preservation,
      notably net zero differential pressure fixation of the leaflets, with
      antimineralization treatment using 2-amino-oleic acid (AOA). METHODS: A total of
      158 Mosaic valves was implanted; 152 in patients aged over 70 years, and six in
      patients aged <70 years with contraindications to anticoagulant therapy. Mean age
      was 73.7 years. All valves were implanted in the supraannular position. Thirty
      two patients (20%) required concomitant procedures, including coronary
      revascularization, ascending aorta replacement and/or mitral annuloplasty.
      Postoperative anticoagulation (heparin) was prescribed for ten days, followed by
      antiplatelet therapy. No long-term oral anticoagulants were prescribed, except in
      some patients with atrial fibrillation. The follow up included routine clinical
      and blood work-up, and echocardiography at six months and one year after surgery.
      RESULTS: There were seven early (0-30 days) and five late deaths (>30 days). One
      death was caused by a hemorrhagic stroke at three months in a patient without
      anticoagulant or antiplatelet therapy. No thromboembolic complications or
      structural valve deterioration were observed during follow up. At two years,
      freedom from endocarditis and reoperation was each 99.6%. NYHA class was
      excellent, with 98% of patients in class I or II at one year. Patient survival
      was 92% at two years. Hemodynamically, the valve was performing well, with mean
      systolic gradients of 13.6, 13.2, 12.6 and 9.6 mmHg for the 21, 23, 25 and 27 mm
      valves, respectively. There was no evidence of structural valve deterioration.
      CONCLUSION: Long-term evaluations are mandatory to confirm the durability of any
      new bioprosthetic valve. Satisfactory early clinical and hemodynamic results with
      the new Mosaic bioprosthesis warrant its continued implantation in the aortic
      position for patients over the age of 70 years.

PMID- 11297204
TI  - Twelve years' clinical experience with the CarboMedics prosthetic heart valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The CarboMedics bileaflet prosthetic heart valve
      was first implanted as part of a prospective clinical study at the authors'
      institution in November 1987. The patient cohort included was part of a
      multicenter trial set up by the manufacturer for an FDA application. The present
      report details findings over a 12-year period, with a continuous follow up on
      this patient cohort. METHODS: Between November 1987 and August 1990, 132 patients
      (68 males, 64 females; median age 56 years; range 12-74 years) received a
      CarboMedics heart valve prosthesis. All patients were included in the study,
      whether surgery was elective or emergency, first time or reoperation. There were
      69 aortic, 49 mitral and 12 double (aortic + mitral) valve replacements. Two
      patients had isolated tricuspid valve replacement. Concomitant surgery was
      performed in 15 patients. Anticoagulation with warfarin was started on
      postoperative day 1. After discharge, patients were examined regularly as
      outpatients for up to five years. Subsequent follow up was obtained prospectively
      by questionnaires to the patients' general practitioner, or by telephone calls.
      Actuarial estimates of survival and freedom from morbid events were calculated
      using the Kaplan-Meier method; 95% confidence limits for the distribution
      function were calculated according to the Greenwood formula. RESULTS: Complete
      follow up information was available for 94% of the patients; total follow up was
      1,014.3 patient-years (pt-yr). Actuarial survival at 12 years was 62 +/- 0.5%
      overall (61 +/- 6.5% for aortic; 66 +/- 7.5% for mitral; 65 +/- 14.0% for double
      valve replacements). Actuarial rates of freedom from complications were: valve
      thrombosis 100%, embolism 92 +/- 2.8%, and anticoagulant-related bleeding 77 +/-
      5.6%. The linearized rates per 100 pt-yr were: embolism 0.89 (aortic 0.74, mitral
      1.30); anticoagulant-related bleeding 2.56; paravalvular leakage overall 0.20
      (aortic 0.37); prosthetic valve endocarditis overall 0.20 (aortic 0.37). There
      was no hemolysis, prosthetic valve dysfunction or structural deterioration.
      CONCLUSION: Over a 12-year time frame, the CarboMedics prosthetic heart valve has
      proven to be a highly reliable device with no structural failures, and a low
      incidence of valve-related complications.

PMID- 11297205
TI  - Long-term results with St. Jude Medical and CarboMedics prosthetic heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The clinical evaluation and comparison of St.
      Jude Medical (SJM) and CarboMedics (CM) prosthetic heart valves implanted between
      1988 and 1997 is presented. METHODS: In total, 648 SJM valves were implanted in
      641 patients, and 601 CM valves in 591 patients. There were 684 mitral valve
      replacements, 256 aortic valve replacements, 252 mitral and aortic (double) valve
      replacements, 16 triple valve replacements, and 41 other tricuspid-related valve
      replacements. Total follow up was 98%. The overall incidence of valve-related
      events was compared before and after establishment of a 'valve clinic' in 1993.
      RESULTS: The overall hospital mortality was 3.4%; late mortality was 8.2%. The
      five- and ten-year survival for all patients was 92.1% and 86.2%, respectively.
      There were 31 episodes of thromboembolism in 27 patients (including valve
      thrombosis in three), 21 episodes of bleeding events in 20 patients, and 18 re
      replacements of implanted valves. No structural valve deterioration was observed.
      Freedom from thromboembolism was 97.8% at five years and 96.3% at ten years;
      freedom from bleeding episodes was 98.1% and 97.6%, respectively. In terms of
      hospital and late mortality, and incidence of thromboembolism, hemorrhagic
      episodes and structural valve failure, no statistically significant differences
      were found between the SJM and CarboMedics patient groups. Freedom from
      thromboembolism was 96.7% at five years before initiation of an intensive follow
      up program, and 99.0% thereafter (p = 0.031). In contrast, freedom from bleeding
      episodes fell from 99.3% to 96.1% during the same time period (p = 0.0004).
      CONCLUSION: Both the SJM and CM prosthetic heart valves performed well in our
      study, and no discernible differences in clinical performance of the two valves
      were detected. The intensive follow up program resulted in a reduced incidence of
      thromboembolism, but an increased number of bleeding complications. An optimum
      anticoagulation regimen to manage these two conflicting problems has yet to be
      elucidated.

PMID- 11297206
TI  - The CarboMedics supraannular top hat valve improves prosthesis size in the aortic
      root.
AB  - BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement can result in patient
      valve mismatch and attenuated left ventricular remodeling. Using CarboMedics
      mechanical valves, we examined if the supraannular Top Hat prosthesis provided a
      size advantage over the intraannular valve. METHODS: Seventeen patients with
      aortic stenosis and aortic root < or = 23 mm were randomized to receive a
      CarboMedics supraannular Top Hat valve (n = 7) or an intraannular valve (n = 10).
      Doppler echocardiography was performed preoperatively, and after three months.
      RESULTS: There was no difference in aortic annulus size, but mean prosthesis size
      was significantly larger in the Top Hat group than in the intraannular group
      (25.00 mm versus 21.60 mm); the mean size improvement for Top Hat patients was
      3.14 mm. After three months, all patients had excellent functional improvement
      and low transvalvular pressure gradients, with slightly higher effective valve
      opening area in the Top Hat group. CONCLUSION: The supraannular Top Hat valve
      provides an advantage of one to two sizes over the intraannular valve, and
      improves the effective valve opening area. Both valves offer favorable
      hemodynamic performance and functional improvement.

PMID- 11297207
TI  - Risks of fracture of Bjork-Shiley 60 degree convexo-concave prosthetic heart
      valves: long-term cohort follow up in the UK, Netherlands and USA.
AB  - BACKGROUND AND AIM OF THE STUDY: Approximately 82,000 Bjork-Shiley convexo
      concave (BSCC) 60 degree prosthetic heart valves were implanted in patients
      worldwide between 1979 and 1986. Outlet strut fractures (OSF) of some of the
      valves were first reported shortly after their introduction. Here, the
      determinants of OSF are examined, and the between-country variation and long-term
      risk are assessed. METHODS: Cohorts of patients in the UK, Netherlands and USA
      with 15,770 BSCC 60 degree heart valves were followed up to 18 years for the
      occurrence of OSF. RESULTS: Crude rates of OSF were highest in the UK (0.18% per
      year), intermediate in the Netherlands (0.13%), and lowest in the USA (0.06%),
      although risk factor adjustment reduced the inter-country differences.
      Furthermore, in the UK and Netherlands, OSF rates (particularly for mitral
      valves) declined with time since implantation, and between-country differences
      were considerably diminished 10 or more years post implantation. The risk of OSF
      decreased steadily with advancing patient age. Fracture rates were lower among
      women than men, and also varied significantly with valve size and position and
      OSF status of other valves in the same shoporder. CONCLUSION: This long-term
      follow up of BSCC 60 degree heart valve patients indicates that risk factors for
      valve fracture are generally similar in the UK, Netherlands and USA. It also
      identifies a strong association between fracture risk and age, newly reveals
      gender-related differences, and shows that the risk of valve fracture persisted,
      albeit at a reduced rate, into the 1990s.

PMID- 11297208
TI  - Self-reported quality of life and health among Bjork-Shiley convexo-concave
      prosthetic heart valve patients.
AB  - BACKGROUND AND AIM OF THE STUDY: The risk of fracture of Bjork-Shiley convexo
      concave (BSCC) prosthetic heart valves has resulted in consideration of
      prophylactic explantation and replacement for patients with high-risk valves.
      Little information exists on perceived quality of life, health status, and
      serious morbidity among BSCC patients, including those who have undergone
      explantation. METHODS: Self-administered questionnaires were completed by a
      cohort of 585 BSCC patients who participated in an X-ray imaging study to detect
      precursors to valve fracture up to seven years (average 3.9 years) previously.
      Responses from 31 explant patients were contrasted with those from 554 BSCC
      patients in whom explant surgery was not attempted. RESULTS: Perceived quality of
      life and health status and risk of hospitalization after participating in the
      imaging study varied considerably among patients, but on average tended not to
      differ significantly between those with and without explants. A slightly greater
      proportion of explantees tended to report both improved health status and high
      rates of heart attack and pacemaker implantation. The health status of these
      patients was, in general, considerably worse than previously reported among valve
      implant patients. Over half the cohort were hospitalized during follow up, and
      half were unable to walk up more than one flight of stairs without shortness of
      breath. CONCLUSION: The less than optimal health status of most BSCC patients and
      relatively high rates of morbidity should be taken into account when considering
      potential explantation of the valves.

PMID- 11297209
TI  - Fracture embolization of a Tekna mitral prosthesis: case report.
AB  - The modified Duromedics-Tekna bileaflet pyrolitic carbon mechanical prosthesis
      was reintroduced by Baxter in 1990. This report details the first case of sudden
      leaflet fracture of a Tekna mitral valve five years after implantation, which was
      managed successfully by replacement with a St. Jude Medical mechanical
      prosthesis. The fracture had occurred transversely, with the fragments embolizing
      to the terminal aortic bifurcation and the left common femoral artery. These were
      localized by computed tomography and removed two days after valve replacement.

PMID- 11297210
TI  - Low-dose aprotinin in heart valve reoperations.
AB  - BACKGROUND AND AIM OF THE STUDY: Aprotinin is effective in promoting hemostasis,
      notably in cardiac surgery with cardiopulmonary bypass. Its efficacy has been
      shown in coronary bypass graft operations. However, few reports exist of
      aprotinin use in valve operations, and in those studies only the full dose was
      used. Thus, our aim was to evaluate the effects of low-dose aprotinin in patients
      undergoing heart valve reoperation. METHODS: Eighteen patients having reoperative
      valve surgery received 10(6) KIU aprotinin after induction of anesthesia, and a
      further 10(6) KIU in the pump prime. A group of 18 similar patients who were
      operated on but did not receive aprotinin were used as controls. RESULTS: A
      significant reduction in postoperative blood loss (approximately 470 ml) occurred
      in patients receiving aprotinin. These patients also presented less postoperative
      bleeding than untreated patients in 70.4% of cases. No adverse effects of the
      drug were noted, except for one case of allergic reaction. CONCLUSION: The
      systematic use of low-dose aprotinin should be considered in valve reoperation,
      except in cases of re-exposure to the drug, or allergic reaction.

PMID- 11297211
TI  - The sensitivity of indicators of thrombosis initiation to a bileaflet prosthesis
      leakage stimulus.
AB  - BACKGROUND AND AIM OF THE STUDY: The recent clinical history and experimental
      studies of the Medtronic Parallel (MP) valve suggest that bileaflet valve leakage
      flow is a primary initiator of thrombosis. These studies investigated the effects
      of physiologic leakage flow through a MP valve on various markers of blood
      damage. METHODS: A centrifugal pump was used to drive whole, human blood
      anticoagulated with PPACK through a circuit containing a MP 27 mm valve in the
      closed position (experimental runs) or a MP 27 mm valve in the open position
      (control runs). Samples were taken at set time intervals after the start of the
      pump. These samples were analyzed by cell counting, flow cytometry, and ELISA.
      RESULTS: Cell counts remained relatively constant in both the experimental and
      control runs. Increases in plasma hemoglobin concentration and the percentage of
      glycophorin A-positive fragments in the cell population were not significant in
      either the experimental or the control runs. Plasma platelet factor 4 activity
      and the percentage of the CD41-positive population which was positive for annexin
      V increased significantly (p <0.05) in the experimental runs compared with the
      control runs. CONCLUSION: The results indicate that bileaflet valve leakage flow
      causes significant platelet disruption, that erythrocytes are more resistant to
      disruption by leakage flow than platelets and granulocytes, and that annexin V
      binding to platelets and plasma platelet factor 4 activity are more sensitive
      markers of leakage induced blood damage than plasma hemoglobin concentration.

PMID- 11297212
TI  - Digital particle image velocimetry investigation of the pulsating flow around a
      simplified 2-D model of a bileaflet heart valve.
AB  - BACKGROUND AND AIM OF STUDY: Strong interactions are believed to exist between
      the pulsating valvular flow and the valve leaflet motions. Hinge position,
      indicated by d/W (d = distance between the two axes of the hinge pivots; W =
      width of the testing section in the middle plane), plays a critical role in MHV
      performance. An optimized hinge position for a bileaflet heart valve can be
      identified as a design criterion for better valve performance. METHODS: A two
      dimensional (2-D) digital particle image velocimetry (DPIV) system was used to
      map the transient flow field of a simplified 2-D model of a bileaflet heart valve
      with a hydraulic diameter enlarged three-fold under pressure waveforms which was
      expanded based on Womersley number and Euler number considerations. Six different
      hinge positions were investigated. RESULTS: At extreme hinge positions (d/W <0.2
      or d/W >0.3), large-scale and long-duration stagnation of flow was found in the
      central orifice, and instability and highly disturbed flow was noted in plots of
      velocity vectors. CONCLUSION: The transient flow pattern in the vicinity of the
      valve was greatly affected by the hinge position of moving leaflets. An optimum
      d/W in the range 0.2-0.3 yielded good velocity field and opening and closing
      behaviors.

PMID- 11297213
TI  - Computational fluid dynamics study of a protruded-hinge bileaflet mechanical
      heart valve.
AB  - BACKGROUND AND AIM OF THE STUDY: Following clinical experience with the Medtronic
      Parallel bileaflet mechanical heart valve, considerable interest has been shown
      in investigating fluid mechanics inside the hinge socket. Most of these studies
      involved hinges that are recessed into the valve housing, such as the St. Jude
      Medical (SJM), CarboMedics, Sorin and On-X bileaflet mechanical heart valves. The
      aim of this study was to investigate the flow fields of a protruded hinge under
      steady flow conditions, with the occluder in its fully open position.
      Computational fluid dynamics (CFD) simulation using the Fluent 4.4.7 commercial
      solver was applied in this investigation. This protruded hinge mechanism for
      pivoting the occluder is an in-house design from the Cardiovascular Dynamics
      Laboratory, Nanyang Technological University. METHODS: The Fluent 4.4.7 code was
      run on a Silicon Graphic Inc. computer (4-CPUx185 MHz) in the CFD simulation. A
      body-fitted coordinates (BFC) grid was generated to cover the entire valvular
      flow domain, including the interior of the hinge and leaflet. Clearance between
      the leaflet and pivot housing was 50-70 microm. In the vicinity of the protruded
      hinge, mesh cells were small compared with hinge dimensions. A power law
      distribution of grid points was applied to optimize the number of cells used to
      cluster the entire flow field. The overall computational flow domain of the valve
      channel, including the floating leaflet and immersed hinge, was approximately
      170,000 cells in total. Inside the hinge socket, approximately 10,000 cells were
      generated. A comparative model with recessed hinge that resembled the SJM valve
      hinge design was modeled. Due to geometric difficulties, an unstructured grid
      scheme was applied. Great attention was focused within the hinge pocket, in
      particular to the clearance between the hinge pivot and leaflet. A total of 2
      million cells was generated for the whole computational flow domain. RESULTS:
      Under steady flow conditions, with the leaflet fixed in an open position, the
      protruded hinge design yielded a pair of small vortices that formed behind the
      stoppers. A low-magnitude velocity was observed inside the hinge clearance.
      Vortices developed behind the protruded stopper. Migrating flow was noted beneath
      the leaflet clearance as a result of pressure difference across the leaflet. For
      the recessed hinge design, reverse flow dominated the inside of the hinge socket,
      and developed into a pair of vortices at high Reynolds number. CONCLUSION: The
      protruded hinge mechanism was designed to expose the overall hinge region to the
      mainstream flow for a positive washing effect. Flow in this protruded hinge
      design is, in general, found to be three-dimensional. Initial results under
      steady flow conditions showed low laminar and turbulent shear stress, while the
      hinge clearance was well washed.

PMID- 11297214
TI  - In-vitro measurements of the regurgitation of mechanical mitral heart valve
      prostheses in case of atrial fibrillation.
AB  - BACKGROUND AND AIM OF THE STUDY: The characterization of heart valve prostheses
      requires regurgitation tests to be conducted in pulsatile flow. Although tests
      are generally conducted in accordance with hemodynamic conditions of a healthy
      young man, heart valve implantation is often associated with other pathology,
      such as atrial fibrillation. To run more realistic trials, four mechanical heart
      valve prostheses were tested with, and then without, atrial contraction. METHODS:
      The dual activation simulator (DAS) allow simulation of physiologically normal
      and pathological flows through the mitral valve. The DAS comprises silicon-based
      cavities, is activated by pumps, and was equipped successively with monoleaflet
      (Bjork-Shiley, Medtronic Hall) and bileaflet (St. Jude Medical, CarboMedics)
      valves. Each valve (mitral, size 27 mm) was tested under two conditions (with and
      without atrial contraction) at a mean flow rate of 3 l/min of glycerol/water
      solution (analog blood viscosity). RESULTS: Leakage volumes were of the same
      magnitude as the precision of the instruments. Respectively, closing volumes
      increased from normal conditions to atrial fibrillation from 3.2 to 5.1 ml for
      Bjork-Shiley, from 4.6 to 6.3 ml for Medtronic Hall, from 5 to 6.6 ml for St.
      Jude Medical, and from 5.2 to 5.4 ml for CarboMedics. The standard deviation was
      below the precision of measurements (+/- 0.5 ml). CONCLUSION: Without atrial
      contraction, the valves seemed to be closed by backward flow only, thus
      confirming earlier reports. This study showed that different heart valves behave
      differently in pathological situations with regard to their design; this must be
      considered when selecting a valve for implantation.

PMID- 11297215
TI  - The influence of ventricular input impedance on the hydrodynamic performance of
      bioprosthetic aortic roots in vitro.
AB  - BACKGROUND AND AIM OF THE STUDY: Hydrodynamic function testing using pulsatile
      flow simulators provides a valuable means of comparative assessment of heart
      valves in vitro. The majority of pulsatile flow simulators consist of modular
      rigid chambers and a positive displacement pump with an infinite input impedance,
      in which the inertia of the test fluid results in pressure oscillations when the
      valves under test are opening and closing. For mechanical and stented
      bioprosthetic valves these pressure oscillations decay quickly. However, due to
      the highly compliant nature of tissue roots, the resulting pressure and flow
      oscillations are extreme and extend throughout systole. With increasing interest
      in the use of free-sewn roots and valves it is most desirable to improve this
      hydrodynamic model. The aim of this study was to investigate the influence in
      changes in ventricular input impedance on the hydrodynamic characteristics of
      free-sewn aortic roots and stented valves. METHODS: The Leeds pulsatile flow
      simulator was modified to incorporate additional compliance chambers in the form
      of a viscoelastic impedance adaptor (VIA) at the pump/ventricular interface. Six
      23 mm bioprosthetic aortic roots fixed with 0.5% buffered glutaraldehyde at zero
      pressure, and a size 23 mm stented porcine aortic bioprosthesis were tested in
      this modified simulator, at the conditions of maximum and minimum input
      compliance. RESULTS: The pressure and flow waveforms for the fixed aortic roots
      showed considerable differences at the conditions of maximum and minimum input
      compliance. Indeed, the extreme pressure oscillations observed at minimum
      compliance (infinite input impedance) were not present at maximum compliance, and
      the forward flow waveform was much smoother. In contrast, for the stented valve,
      the differences in the pressure and flow waveforms between maximum and minimum
      input compliance were minimal, but this was expected due to the lack of
      compliance in the stented valve itself. In addition, the flow and pressure
      waveforms at maximum compliance in the VIA were comparable for the fixed aortic
      roots and the stented bioprosthesis, thus allowing direct comparison of the
      characteristics of these two different devices. Using test conditions of maximum
      input compliance, effective orifice area for the roots was 1.69 cm2 compared with
      1.47 cm2 for the stented valve. CONCLUSION: An appropriate physiological model
      for the hydrodynamic testing of compliant tissue roots has been established.

PMID- 11297216
TI  - Native valve salvage for post-traumatic tricuspid regurgitation.
AB  - We describe two cases of successful management by native valve salvage of an
      uncommon tricuspid valve regurgitation following blunt chest trauma. The two
      patients were diagnosed 13 years and six years, respectively, after the trauma.
      In both cases, tricuspid valvular insufficiency was caused by anterior leaflet
      prolapse due to chordal and papillary muscle rupture associated with annular
      dilatation. Operative repair with implantation of artificial chordae, papillary
      muscle reinsertion and ring annuloplasty resulted in complete recovery. The need
      for increased awareness of this lesion in patients suffering blunt chest trauma
      is emphasized, and the relevant literature reviewed.

PMID- 11297217
TI  - Is there a relationship between influenza vaccinations and risk of melanoma? A
      population-based case-control study.
AB  - The aim of the present case-control study was to ascertain whether, in adults,
      yearly repeated anti-influenza vaccinations (AIV) enhance protection against
      cutaneous melanoma (CM), as do repeated febrile infections. Ninety-nine new cases
      of histologically confirmed CM and 104 healthy controls (matched to cases for
      sex, age, and skin colour) selected from the general population were examined in
      order to ascertain their skin type, the number of nevi on both arms, and the
      intensity of freckles on the face and the arms; in these subjects, a structured
      questionnaire was used to obtain information on age, sex, education, social
      class, exposure and susceptibility to sunlight, history of febrile infectious
      diseases, and vaccinations. The odds ratio (OR) and the 95% confidence interval
      (CI) were estimated by commonly used methods and by fitting models of logistic
      regression. The risk of CM was reduced in subjects with a history of febrile
      (temperature above 38.5 degrees C) infections in the 5 years prior to CM surgery
      (cases) or interview (controls), but was increased in those with voluntary
      exposure to sunlight in tropical countries. By holding the above factors constant
      at logistic regression analysis, it was found that a history of repeated AIV (3-5
      times in the last 5 years) halved the risk (OR: 0.43; CI: 0.19-1.00; p < 0.05).
      With the variable 'nevi on arms' included, the protective influence of repeated
      AIVs was observed in a similar magnitude. The inverse relationship found between
      melanoma and influenza vaccinations is unlikely to have depended on a bias, even
      if based on replies in a questionnaire, because neither the interviewers nor the
      interviewers were informed in advance of the working hypothesis.

PMID- 11297218
TI  - Rise and fall of asthma-related mortality in Italy and sales of beta2-agonists,
      1980-1994.
AB  - We performed this study with the aims of describing the trend of asthma-related
      mortality in Italy between 1980 and 1994, and to evaluate the relationship
      between sale estimates of beta2-agonists drugs and mortality from asthma. For
      asthma mortality we used data provided by National Institute of Statistics, for
      sale estimates of beta2-agonists we used data provided by IMS HEALTH. We
      calculated the gender specific age-standardized incidence rates of asthma-related
      deaths for all ages and for age classes. We found that estimates for asthma
      related mortality steadily increased between 1980 and 1987 in both sexes, and
      thereafter decreased. In people, aged between 34 and 64 and over 64, death rates
      in males were significantly higher than in females while the rates in those aged
      less than 34, were mostly similar in both gender. The overall exposure to beta2
      agonists (alone and in combination) increased from 1980 to 1990, remained stable
      between 1990 and 1993, and increased steeply in 1994. We conclude that asthma
      related death rates have declined since the mid-1980's. This decline has been
      more pronounced in males and in the older ages, while the rates in younger
      patients of both genders have remained nearly unchanged. Our data do not
      substantiate the hypothesis of an increased risk of asthma-related mortality
      associated to the use of inhaled beta2-agonists in general nor fenoterol or
      salbutamol in particular.

PMID- 11297219
TI  - Heavy coffee drinking and the risk of suicide.
AB  - Earlier research has implicated coffee drinking as a possible protective factor
      for suicide. We followed-up 43,166 subjects for the mean 14.6 years, and 213
      suicides were committed. Daily coffee drinking had a J-shaped association with
      the risk of suicide. Using the Cox model we controlled for potential covariates,
      and found that among heavy coffee drinkers (> or = 8 cups/day) the risk of
      suicide was 58% higher compared with more moderate drinkers.

PMID- 11297220
TI  - Parental recall of birthweight: a good proxy for recorded birthweight?
AB  - Recent evidence suggests potential associations between birthweight and disease
      in later life. For resource or other reasons recorded birthweight may be
      unavailable to researchers who have access to uniquely relevant outcome data. The
      present study examined the validity of parental recall of birthweight. Parents of
      1015 males and females aged 12 and 15 years participating in the Young Hearts
      Study (a cluster random sample of 1015 males and females aged 12 and 15 years
      from post-primary schools in Northern Ireland) completed a questionnaire which
      included a question about their child's birthweight. The answer provided was
      compared with recorded birthweight obtained from archived computerised child
      health records with a cut-off point for inaccurate reporting set at +/- 227 g
      (1/2 lb). The influence of social class and weight at birth on accuracy of recall
      was also determined. A total of 84.8% of parents accurately recalled their
      child's birthweight to within 227 g. Parents from non-manual occupation social
      classes recalled birthweight more accurately than those from manual occupation
      social classes (88.0 vs. 82.6% accurate: chi2 = 4.81, p = 0.03). Parents of low
      birthweight infants tended to recall their birthweight less accurately than
      parents of normal weight infants: 76.1% accurate compared to 86.1% accurate: chi2
      = 3.54, p = 0.06. Parents of high birthweight infants recalled their birthweight
      less accurately than parents of normal weight infants: 78.5% accurate: chi2 =
      3.94, p = 0.05. In conclusion, parentally recalled birthweight may be a suitable
      proxy for recorded birthweight for population based research into disease in
      childhood and adolescence.

PMID- 11297221
TI  - Socioeconomic status, overweight and obesity in prepuberal children: a study in
      an area of Northern Italy.
AB  - The aim of this study was to determine whether socio-economical status (SES) is
      associated with overweight and obesity in prepuberal children. In an area of
      North-Western Italy a sample of 1420 children, aged 10-11 years, had his/her
      height and weight recorded, (overweight and obesity were defined, respectively,
      as relative body weight > or = 120% and > or = 140%), and parents were requested
      to compile a questionnaire exploring some demographic and social conditions. 23%
      of the sample resulted overweight or obese. Prevalence rate ratios (PRR) of
      overweight and obesity (together) were calculated, adjusting for parents' age,
      parents' area of birth, and school district. PRR for mother's lowest educational
      level compared to the highest was 1.59 (95% CI: 1.19-2.13), while for father's
      education was 1.21 (0.90-1.63). PRRs for 'unemployed' or 'manual' mother compared
      to 'upper non manual' were respectively 1.83 (1.20-2.79) and 2.20 (1.31-3.68),
      while for 'unemployed' or 'manual' father were 2.63 (1.97-2.63), and 1.63 (1.27
      2.09). The cultural resources of the mother, and the economical resources of the
      family seem to influence the prevalence of weight gain in prepuberal children.
      This should be taken into account when planning programs for the prevention or
      reduction of obesity in children.

PMID- 11297223
TI  - The feasibility of combining data from routine Hospital Discharge and Causes-of
      Death Registers for epidemiological studies on stroke.
AB  - We assessed the validity of hospital discharge data on stroke in Finland and the
      feasibility of linked hospital discharge and causes-of-death data for
      epidemiological studies using the FINMONICA Stroke Register as the reference. The
      results showed that such data can, with some caution, be used for incidence
      studies and for identifying first stroke events. They cannot, however, be used
      for assessing secular trends in all stroke events.

PMID- 11297222
TI  - Risk factors for congenital heart diseases in Alexandria, Egypt.
AB  - A matched case control study has been conducted in the children's hospitals in
      Alexandria, Egypt, during 2 years-period, aiming at investigating the risk
      factors for the occurrence of congenital heart diseases. Our results showed that
      the significant risk factors for developing any type of congenital heart disease
      and ventricular septal defects were: older paternal age at birth, positive
      consanguinity, positive family history, female sex hormones, irradiation,
      hazardous maternal occupation, diabetes mellitus and suburban or rural residence.
      However, some environmental/teratogenic factors were not implicated in the
      etiology of atrial septal defects or pulmonary stenosis. These findings strongly
      suggest that environmental factors vary according to the specific type of
      congenital heart disease. This study emphasizes on the need to instruct the
      public about the importance of pre-marital counseling and the deleterious effects
      of various teratogens in the environment.

PMID- 11297224
TI  - Human factors in the causation of road traffic crashes.
AB  - Road traffic crashes (RTCs) are responsible for a substantial fraction of
      morbidity and mortality and are responsible for more years of life lost than most
      of human diseases. In this review, we have tried to delineate behavioral factors
      that collectively represent the principal cause of three out of five RTCs and
      contribute to the causation of most of the remaining. Although sharp distinctions
      are not always possible, a classification of behavioral factors is both necessary
      and feasible. Thus, behavioral factors can be distinguished as (i) those that
      reduce capability on a long-term basis (inexperience, aging, disease and
      disability, alcoholism, drug abuse), (ii) those that reduce capability on a short
      term basis (drowsiness, fatigue, acute alcohol intoxication, short term drug
      effects, binge eating, acute psychological stress, temporary distraction), (iii)
      those that promote risk taking behavior with long-term impact (overestimation of
      capabilities, macho attitude, habitual speeding, habitual disregard of traffic
      regulations, indecent driving behavior, non-use of seat belt or helmet,
      inappropriate sitting while driving, accident proneness) and (iv) those that
      promote risk taking behavior with short-term impact (moderate ethanol intake,
      psychotropic drugs, motor vehicle crime, suicidal behavior, compulsive acts). The
      classification aims to assist in the conceptualization of the problem that may
      also contribute to behavior modification-based efforts.

PMID- 11297225
TI  - Are cognitively impaired individuals adequately represented in community surveys?
      Recruitment challenges and strategies to facilitate participation in community
      surveys of older adults. A review.
AB  - BACKGROUND: Dementia is the most important age-related disorder and subject to a
      substantial body of epidemiological research. However, field work in elderly
      populations faces special challenges which may reduce response rates and
      invalidate survey results. Therefore, this paper will review more recent
      prevalence studies of dementia to examine how recruitment issues and their
      influence on the study outcome have been addressed. METHODS: Field studies of the
      elderly with the main focus on prevalence of dementia published over the last 10
      years will be systematically reviewed. The review concerns sampling frames, ways
      to include institutionalised individuals, response rates and strategies to deal
      with special challenges of field work in elderly populations such as mortality,
      fragility and sensory impairment. Furthermore, papers were evaluated regarding
      the extent to which recruitment outcomes were discussed. RESULTS: The literature
      is characterised by a disregard of recruitment issues to a varying extent.
      Mortality, functional dependency and sensory impairment (all positively related
      to dementia) are barely taken into account in the study design and rarely
      discussed. As a consequence, cognitively impaired individuals are likely to be
      underrepresented in most community studies. CONCLUSION: Strategies to deal with
      special challenges of field work in the elderly in a systematic manner and to
      facilitate participation in population surveys of the elderly are crucial and
      will be outlined. Communication on recruitment issues is essential to improve the
      validity of study outcomes.

PMID- 11297227
TI  - Estimating incidence of bacterial meningitis with capture-recapture method, Lazio
      Region, Italy.
AB  - To estimate the incidence of bacterial meningitis in the Lazio Region, including
      the city of Rome, and to assess the quality of the surveillance systems, we
      adopted a multiple-capture model by merging cases from three sources available in
      1995-1996: the Notifiable Disease Surveillance (NDS) system, the Special Hospital
      Surveillance (SHS) system and the Hospital Discharge (HD) registry. A medical
      record revision was carried out to confirm the cases of bacterial meningitis. A
      total of 199 individuals was classified as probable or confirmed cases of
      bacterial meningitis in 1995-1996. In this period, the incidence of reported
      meningitis was 3.8/100,000 (population = 5,209,633). The log-linear model yielded
      a total estimated number of 236 cases (95% confidence interval (CI): 206-306),
      the estimate of incidence reaching the value of 4.5/100,000. Hospital Discharge
      registry showed the highest sensitivity (77%), the SHS system the highest
      positive predictive value (83%). In 1997-1998, the meningitis surveillance was
      integrated with an additional laboratory-based source and yielded 326 cases, with
      an incidence of reported cases of 6.3/100,000. Laboratory surveillance, involving
      115 (92%) public hospitals and 84 (57%) private clinics, contributed 35 (27%)
      cases in addition to those notified to NDS (n = 130). Multiple-capture models, in
      our experience could estimate the bacterial meningitis incidence with a very good
      approximation. In order to improve both sensitivity and positive predictive value
      of surveillance, hospital and public health sources should be integrated with
      laboratory-based system.

PMID- 11297226
TI  - Allergic bronchopulmonary aspergillosis in Italian cystic fibrosis patients:
      prevalence and percentage of positive tests in the employed diagnostic criteria.
AB  - The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in cystic
      fibrosis (CF) patients is difficult to determine because the data in the
      literature are not homogeneous or comparable. ABPA and CF have similar clinical
      symptoms which make diagnosis difficult and underestimate the real dimensions of
      the problem. We conducted an epidemiological study on 3089 Italian CF patients to
      determine the prevalence of ABPA in Italy and verify the percentage of positive
      tests in the employed diagnostic criteria. Our results indicate that the
      prevalence of ABPA in Italian CF patients is 6.18%, mainly in adolescents and
      young adults. ABPA is diagnosed using clinical symptoms (presence of episodic
      bronchial obstructions or typical radiographic features) and on the basis of
      other criteria which can only be partially fulfilled in paediatric patients.
      Among the diagnostic tests the most sensitive are the total IgE (84.5%), specific
      IgE anti-Aspergillus fumigatus (81.6%) and the prick test (68.3%). In the absence
      of clinical symptoms and gold standard diagnostic tests, serological positivity
      and/or the skin test are not sufficient evidence to confirm the presence of ABPA.

PMID- 11297228
TI  - Risk factors in falls among the elderly according to extrinsic and intrinsic
      precipitating causes.
AB  - The aim of this prospective cohort study was to identify the risk factors
      involved in falls in 190 elderly residents of two geriatric centres in Granada
      (Andalusia, Spain). Because different types of falls may be associated with
      different factors, falls were classified according to the precipitating cause,
      either extrinsic or intrinsic. The incidence density and the ratios for crude and
      adjusted density were calculated. Cox proportional risk analysis was used to
      calculate adjusted incidence density ratios. Of the 121 falls identified, 63
      (52.1%) had a extrinsic precipitating cause, 43 (35.5%) had an intrinsic
      precipitating cause, and no precipitating cause was determined in 15 falls. The
      rate of falls with an extrinsic precipitating cause was 0.39 per person per year,
      while falls with an intrinsic precipitating cause showed a frequency of 0.27 per
      person per year. For falls with an extrinsic precipitating cause, the most
      significant risk factors were: age, diabetes mellitus, a history of falling, and
      treatment with neuroleptics or oral bronchodilators. The number of illnesses
      acted as a protective factor. For falls with an intrinsic precipitating cause,
      the independent risk factors were: age, diabetes, dementia, alterations of gait
      and balance, previous falls, and treatment with digitalins, neuroleptics or
      antidepressants. These results suggest that the susceptibility to a fall with an
      intrinsic precipitating cause is easier to identify and has a greater potential
      for being controlled.

PMID- 11297229
TI  - A review of the Salmonellosis surveillance systems in Italy: evolution during the
      course of time within the international framework.
AB  - This paper focuses on the history of the two systems that have been adopted in
      Italy for the surveillance of Salmonellosis and describes their respective
      characteristics. Both systems have been subsequently modified: (1) The National
      Laboratory-based Surveillance System (NLSS) which was created in 1967 for
      Enteropathogenic Bacteria and subsequently, in 1992, became part of the European
      computerised Laboratory-based Surveillance System of Salmonellae isolates, the
      SALM-NET (Salmonella network); (2) The National Infectious Disease Reporting
      System (NIDRS) which was set up in the 1930s, revised in 1990 and has been used,
      since 1994, along with the Infectious Disease Informative System (IDIS). The
      results obtained with the different surveillance systems are presented: (1) The
      number of isolates from the laboratory surveillance from 1973 to 1997 are
      described. Total Salmonellae isolates have a slope with an increasing trend from
      4372 isolates in 1973 to 15,041 isolates in 1988 drastically dropping to 5479
      isolates in 1990 and increasing again to 13,596 isolates in 1993. Attention is
      given particularly to the epidemiology of S. enteritidis in Italy which increased
      progressively since 1982 (225 isolates) to 5435 isolates in 1994. S. typhimurium
      showed a slightly increasing trend in the period 1973-1988 (from 1694 to 3383
      isolates) then decreased for reaching again previous levels. S. typhi showed a
      marked reduction from 573 isolates in 1973 to 33 isolates in 1996. On the
      contrary, other less frequent serotypes increased. (2) The number of cases of
      Salmonellosis reported during 1971-1997 are also presented. Other Infections by
      Salmonellae increased from 12,516 cases in 1976 (renamed Non Typhoidal
      Salmonellosis in 1990) to more than 20,000 cases in 1992. The number of cases of
      Typhoid Fever and Infections by S. paratyphi are also described. Particular
      attention has to be paid to the parallel trends of Salmonellosis using both
      surveillance systems: number of isolates and number of cases, particularly
      comparing Other Infections by Salmonellae and total Salmonellae isolates: after
      the 1992-1993 peak, an initial decrease was observed.

PMID- 11297230
TI  - Detection of spirochaetes of Borrelia burgdorferi complexe in the skin of cervids
      by PCR and culture.
AB  - To determine whether deer may play a role in the cycle of the Lyme disease
      spirochete Borrelia burgdorferi, we sought evidence for the presence of the
      pathogen in skin of deer and roe deer. Biopsies of 2 mm3 were taken at four
      different levels from nail to tarsus. A total of 50 animals (200 biopsies) were
      shot in the Lyme disease foci of Rambouillet during the hunting season 1995-1996
      and 1996-1997, from the beginning of November to the end of February. Borrelia
      burgdorferi s.l. DNA was detected by PCR in 18 biopsies from 14 animals (28%).
      Borrelia burgdorferi s.str. was predominant (50%), followed by B. garinii (30%)
      and B. afzelii (10%). Multiple infections were detected in four animals: same
      species at different levels or two different species from the same biopsy or from
      different biopsies from the same foot. A total of 125 biopsies were cultivated on
      BSKH medium. Cultures at 160 days revealed immobile spiralled forms in 10
      cultures. One, from a deer killed at the end of December, was confirmed by PCR as
      B. burgdorferi s.str. These results, frequency of detection of spirochetes by PCR
      in the skin, multiple infections and alive spirochetes in biopsies taken out side
      the season of activity of ticks strongly suggest an affinity of Lyme disease
      spirochetes for skin of cervids.

PMID- 11297231
TI  - Prevalence of antibodies to Toxoplasma gondii in the female population of the
      County of Split Dalmatia, Croatia.
AB  - The prevalence of IgG antibodies reactive with Toxoplasma gondii in the female
      population of the County of Split Dalmatia was investigated by enzyme linked
      immunosorbent assay. Of a total of 1109 serum samples collected from female
      subjects, 423 (38.1%) reacted with T. gondii. The frequency of positive sera
      increased with age. Theoretical incidence of congenital toxoplasmosis was
      calculated from the annual increase in cumulative prevalence of antibodies
      between different age groups among the women of childbearing age. The estimated
      theoretical incidence of congenital toxoplasmosis was 1.4 per 100 pregnancies of
      adolescents (16-20 years) and decreased to 0.1% in seronegative pregnant women
      aged 41-45.

PMID- 11297232
TI  - The diverse role of the ETS family of transcription factors in cancer.

PMID- 11297233
TI  - Chlorambucil drug resistance in chronic lymphocytic leukemia: the emerging role
      of DNA repair.
AB  - Various mechanisms have been implicated in nitrogen mustard drug resistance. The
      role of these mechanisms in the development of chlorambucil drug resistance in
      chronic lymphocytic leukemia (CLL) is discussed. We review these mechanisms with
      emphasis on the emerging role of DNA repair, and specifically, recombinational
      repair. Inhibition of these repair processes may lead to new therapies, not only
      in CLL, but in other malignancies as well.

PMID- 11297234
TI  - Lymphangiogenesis and tumor metastasis: myth or reality?
AB  - The metastatic spread of tumor cells is responsible for the majority of cancer
      deaths, and with few exceptions, all cancers can metastasize. Clinical findings
      have long suggested that by providing a pathway for tumor cell dissemination,
      tumor-associated lymphatics are a key component of metastatic spread. It is not
      known, however, whether pre-existing vessels are sufficient to serve this
      function, or whether tumor cell dissemination requires de novo lymphatic
      formation (lymphangiogenesis) or an increase in lymphatic size. Lymphangiogenesis
      has traditionally been overshadowed by the greater emphasis placed on the blood
      vascular system (angiogenesis). This is due in part to the lack of identification
      of lymphangiogenic factors, as well as suitable markers that distinguish blood
      from lymphatic vascular endothelium. This scenario is changing rapidly after the
      identification of the first lymphangiogenic factor, vascular endothelial growth
      factor C (VEGF-C). Increased expression of VEGF-C in primary tumors correlates
      with increased dissemination of tumor cells to regional lymph nodes in a variety
      of human carcinomas. Here I will review what is known about the mechanisms of
      lymphangiogenesis, particularly in the context of metastatic tumor spread, and
      will critically examine the role of VEGF-C in this process. However, despite
      recent progress in this field, it remains to be determined whether inhibition of
      lymphangiogenesis is a realistic therapeutic strategy for inhibiting tumor cell
      dissemination and the formation of metastasis.

PMID- 11297235
TI  - AIS overexpression in advanced esophageal cancer.
AB  - We examined AIS status in digestive tract cancers and found that all eight
      esophageal cancer cell lines (100%) showed AIS/TA-AIS gene overexpression,
      whereas 1 of 12 (8%) gastric cancer and 0 of 14 (0%) colon cancer cell lines
      showed AIS/TA-AIS gene expression. We then confirmed that the AIS gene, not the
      TA-AIS gene, was dominantly expressed in esophageal cancers by reverse
      transcription-PCR. AIS protein was also expressed in AIS gene-positive cell
      lines. Subsequently, we tested AIS gene expression in paired esophageal normal
      tissues and cancers. Twenty-five of 39 (64%) primary esophageal cancers
      demonstrated an obviously higher expression of AIS gene compared to paired normal
      tissues. Moreover, high AIS gene expression was significantly associated with
      lymph node metastases in esophageal cancer (P = 0.0271). These results suggested
      that AIS may be useful as a marker for advanced esophageal cancer.

PMID- 11297236
TI  - Prognostic significance of periodic acid-Schiff-positive patterns in primary
      cutaneous melanoma.
AB  - The patterns of periodic acid-Schiff (PAS) staining of extracellular matrix in
      histological sections of certain melanomas may be predictive of outcome. Recent
      in vitro and molecular genetic data suggest that the appearance of these patterns
      in both uveal and cutaneous melanoma is a function of aggressive tumor cells. We
      studied 96 patients with primary cutaneous melanomas treated at the University of
      Illinois at Chicago who were monitored for disease-free survival. Survival
      probabilities were determined by Kaplan-Meier estimates, and prognostic factors
      were evaluated by multivariate analysis. By univariate analysis, there was a
      significant decrease in disease-free survival among patients whose tumors
      contained parallel with cross-linking or network patterns (PXNs; P = 0.0070).
      Stepwise regression with Cox models that included the combinations of the PAS
      positive patterns, tumor thickness, female gender, ulceration, and age yielded a
      model with thickness and the PAS-positive parallel with cross-linking or
      networks. Despite the relatively small sample size in this study, the detection
      of the PAS-positive parallel with cross-linking or networking in cutaneous
      melanoma was associated with a decrease in disease-free outcome. Additional
      studies of the prognostic significance of these patterns is warranted on larger
      data sets.

PMID- 11297237
TI  - A phase I dose-ranging trial of monthly infusions of zoledronic acid for the
      treatment of osteolytic bone metastases.
AB  - Bisphosphonates are potent inhibitors of bone resorption and provide a
      therapeutic benefit for patients with bone metastases. Zoledronic acid is a
      highly potent, nitrogen-containing bisphosphonate. In the present trial, we
      assessed the safety and tolerability of increasing doses of zoledronic acid and
      its effects on urinary markers of bone resorption in cancer patients with bone
      metastases. Fifty-nine cancer patients with bone metastases were enrolled
      sequentially into one of 8 treatment groups in the core protocol. Each patient
      received a 5-min i.v. infusion of 0.1, 0.2, 0.4, 0.8, 1.5, 2, 4, or 8 mg
      zoledronic acid monthly for 3 months. Patients were monitored for clinical
      findings, adverse events, electrocardiograms, markers of bone resorption, as well
      as routine hematology, blood chemistries, and urinalysis. Thirty patients who
      demonstrated a radiographic response to treatment or stable disease in the core
      protocol were enrolled in a humanitarian extension protocol and continued to
      receive monthly infusions. Zoledronic acid was well tolerated at all dose levels.
      Adverse events reported by >10% of patients included skeletal pain, nausea,
      fatigue, upper respiratory tract infection, constipation, headache, diarrhea, and
      fever. Three patients in the core protocol and one patient in the extension
      protocol experienced grade 3 skeletal pain, "flu-like" symptoms, or
      hypophosphatemia, which were possibly related to treatment; all recovered
      completely. Adverse events were reported with similar frequency across all of the
      dosage groups. Zoledronic acid resulted in sustained, dose-dependent decreases in
      urinary markers of bone resorption. Zoledronic acid was safe and well tolerated
      and demonstrated potent inhibition of bone resorption.

PMID- 11297238
TI  - A phase I study of CNI-1493, an inhibitor of cytokine release, in combination
      with high-dose interleukin-2 in patients with renal cancer and melanoma.
AB  - CNI-1493, an inhibitor of proinflammatory cytokines, was studied in a Phase I
      trial in melanoma and renal cancer patients receiving high-dose interleukin 2 (IL
      2). Objectives of the study were to define the maximum tolerated dose (MTD) and
      toxicity of CNI-1493, to assess its pharmacological effects, and to define its
      pharmacokinetics. Twenty-four patients were treated in sequential cohorts with
      CNI-1493 doses from 2 through 32 mg/m2 daily. Patients first received only CNI
      1493 daily for 5 days. After a 9-day rest, patients received two 5-day courses of
      IL-2 of 600,000 IU/kg every 8 h for up to 14 doses/course plus daily CNI-1493;
      courses were separated by a 9-day rest period. CNI-1493 administered alone was
      well tolerated at doses through 32 mg/m2; MTD was not reached. The only clinical
      toxicity attributed to CNI-1493 was occasional injection-site phlebitis. Grade 1
      creatinine increases occurred in 1 of 7 patients at 4 mg/m2, in 1 of 1 patients
      at 25 mg/m2, and in 3 of 6 patients at 32 mg/m2 CNI-1493 alone. In combination
      with high-dose IL-2, CNI-1493 at > or = 25 mg/m2 seemed to exacerbate IL-2
      induced nephrotoxicity: grade 3 or 4 creatinine increases developed in 3 of 6
      patients at 25 or 32 mg/m2, as compared with 1 of 16 patients at doses < or = 16
      mg/m2. The MTD for CNI-1493 given with high-dose IL-2 was 16 mg/m2. The dose
      limiting toxicity of IL-2 was hypotension in 63% of patients; overall tolerance
      to IL-2 was not improved by CNI-1493. However, relative to changes seen in a
      reference group receiving high-dose IL-2 alone, at doses > or = 4 mg/m2 CNI-1493
      did show evidence of pharmacological activity as an inhibitor of tumor necrosis
      factor production.

PMID- 11297239
TI  - Delayed sodium thiosulfate as an otoprotectant against carboplatin-induced
      hearing loss in patients with malignant brain tumors.
AB  - Carboplatin is effective in the treatment of malignant brain tumors. However,
      when administered in conjunction with osmotic opening of the blood-brain barrier
      (BBB), carboplatin is ototoxic. The purpose of this study was to determine
      whether delayed administration of sodium thiosulfate (STS), given after BBB
      closure, provided protection against carboplatin ototoxicity. Patients underwent
      monthly treatment with intra-arterial carboplatin (200 mg/m2/day x 2) in
      conjunction with osmotic opening of the BBB, for up to 1 year. Audiological
      assessment was conducted at baseline and within 24 h before each monthly
      treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16
      g/m2) 15-min doses, depending on baseline hearing status. The initial group
      received the first STS dose 2 h (or 2 and 6 h) after carboplatin (STS2) and a
      subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4).
      Audiological data were compared with a historical comparison group (HCG) treated
      with carboplatin without STS. Spearman correlation coefficients comparing STS 2
      (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of
      ototoxicity with increased delay in STS (P = 0.0006). On the basis of the
      analysis of hearing levels, there were significant differences among the two STS
      groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank
      test for time to ototoxicity indicated a significant difference between STS4 and
      HCG (P = 0.0018). Delayed STS was effective in protecting against carboplatin
      induced hearing loss. STS delayed to 4 h after carboplatin significantly
      decreased time to development of ototoxicity and rate of ototoxicity when
      compared with HCG.

PMID- 11297240
TI  - Phase I and pharmacological study of two schedules of the antifolate edatrexate
      in combination with cisplatin.
AB  - The antifolate edatrexate has shown moderate activity against cancers of the head
      and neck and non-small cell lung cancer, as has cisplatin. Edatrexate
      demonstrates synergy with cisplatin in transplanted tumor models. This Phase I
      study was designed to evaluate two schedules of administration of cisplatin in
      combination with escalating doses of edatrexate, in a population consisting
      mainly of patients with these two cancers. The starting dose of edatrexate was 40
      mg/m2. Dose escalation was to occur in 10-mg/m2 increments; the planned maximum
      dose level for study was 80 mg/m2. A total of 39 patients were registered. Eleven
      were treated on schedule A: cisplatin 120 mg/m2 every 4 weeks, and edatrexate
      weekly. Twenty-eight patients were assigned to schedule B: cisplatin 60 mg/m2 and
      edatrexate, both given every 2 weeks. On schedule A, the maximum tolerated dose
      of weekly edatrexate was 40 mg/m2, with dose-limiting toxicities of leukopenia,
      mucositis, and renal insufficiency. On schedule B, the maximum tolerated dose of
      biweekly edatrexate was 80 mg/m2, with leukopenia and mucositis as dose limiting.
      For schedule A, pharmacokinetic studies suggested a possible effect of cisplatin
      on the day 8 clearance of edatrexate. Studies on patients on schedule B did not
      show a clear effect of cisplatin on the day 15 edatrexate clearance. On schedule
      A, 5 of 9 evaluable patients had major responses (1 complete); whereas on
      schedule B, 8 of 25 patients had major responses (1 complete). Responses were
      seen in both head and neck and non-small cell lung cancer patients. For Phase II
      studies, use of cisplatin 60 mg/m2 and edatrexate 80 mg/m2, both given biweekly,
      is recommended.

PMID- 11297241
TI  - Interferon alpha-2a therapy in 18 hemangioblastomas.
AB  - Multiple hemangioblastomas (HBs) of the central nervous system (CNS) and retina
      are associated with von Hippel-Lindau disease (VHL) and also predispose
      individuals to renal cell carcinomas and visceral cysts. In VHL, microsurgery or
      radiosurgery cannot prevent new HBs from arising in the CNS or coagulation of
      retinal HBs. Multiple but thus far asymptomatic HBs pose a therapeutic problem.
      IFN-alpha-2a has antiangiogenic activity with an especially favorable effect on
      life-threatening hemangiomas of the liver in children. This is the first study to
      assess the efficacy of IFN-alpha-2a in treatment of asymptomatic HBs of the CNS
      and retina. Four patients (three with VHL) with a combined total of 15 HBs of the
      CNS, 3 HBs of the retina, and 14 renal and 2 pancreatic cysts were treated with
      s.c. IFN-alpha-2a for 12 months at 3 x 10(6) IU, 3 times/week. Baseline workup
      consisted of detailed neurological, ophthalmological, and radiological
      examinations. Follow-up studies at 3, 13, and 21 months were used to monitor the
      response. No de novo HBs were detected during the therapy, but one appeared 9
      months after cessation of IFN-alpha-2a therapy. HBs of the CNS did not shrink
      markedly during the therapy. IFN-alpha-2a may decrease blood flow in HBs as
      suggested by shrinkage and diminished leakage of two retinal HBs. However, the
      therapy did not prevent visceral cysts from growing. The systemic response was
      also monitored by measurement of serum levels of vascular endothelial growth
      factor and erythropoietin, which remained essentially unchanged during the
      treatment. No serious side effects were recorded.

PMID- 11297242
TI  - Effect of food on the oral bioavailability of UFT and leucovorin in cancer
      patients.
AB  - UFT is composed of tegafur (FT), a prodrug of 5-fluorouracil (5-FU), and uracil
      in a fixed combination (1:4). In conjunction with leucovorin, UFT is being
      developed for the first-line oral treatment of metastatic colorectal cancer. The
      effect of food on the oral bioavailability of UFT (2 x 100 mg capsules; dose in
      terms of FT) and leucovorin (2 x 15 mg tablets) was evaluated in a single-dose,
      randomized, two-way crossover study. Patients (n = 25) were assigned to receive
      both drugs after an overnight fast or 5 min after completion of a high-fat meal
      (721 calories) with a 3-day washout period between treatments; then they were
      permitted to continue on oral UFT/leucovorin therapy for safety assessment. UFT
      (300 mg/m2/day as three divided doses) and leucovorin (90 mg/day as three divided
      doses) were given for 28 days. After a 7-day rest, the 28-day cycle was repeated.
      Pharmacokinetics (n = 22 patients) were determined for FT, 5-FU, uracil,
      leucovorin, and 5-methyltetrahydrofolate (an active metabolite of leucovorin).
      The absence of food-effect on peak plasma concentration (CMAX) and the area under
      the curve (AUC) was concluded if the 90% confidence interval for the ratio of the
      treatment means was entirely contained in 0.75-1.33. Administration of UFT with
      food resulted in a 34% decrease in CMAX of FT, whereas the AUC of FT remained
      unchanged. Food decreased the CMAX and AUC values of uracil and 5-FU by 37-76%.
      On the contrary, the CMAX and AUC values of leucovorin and 5
      methyltetrahydrofolate were increased by 14-60% with food. Time to reach CMAX for
      all analytes was significantly (P < or = 0.001) delayed by food. Except for the
      AUCs of FT, the statistical criterion for concluding a lack of food-effect was
      not met. These data suggest that UFT/leucovorin should not be dosed
      simultaneously with food. It is recommended that food should not be consumed for
      1 h before and after an oral dose of UFT and leucovorin in a manner similar to
      pivotal Phase III trials. The 28-day oral regimen of UFT and leucovorin was
      generally well tolerated in the population studied.

PMID- 11297243
TI  - Association of serum endoglin with metastasis in patients with colorectal,
      breast, and other solid tumors, and suppressive effect of chemotherapy on the
      serum endoglin.
AB  - In this report, we present data indicating that the increased serum endoglin
      (EDG; CD105) quantitated by a double-antibody sandwich assay is associated with
      metastasis in patients with solid tumors including colorectal and breast
      carcinomas. In addition, we show that chemotherapy exerts a suppressive effect on
      the serum EDG. EDG is a proliferation-associated cell membrane antigen of human
      vascular endothelial cells. Furthermore, EDG is essential for angiogenesis. We
      generated two anti-EDG monoclonal antibodies (mAbs), termed SN6a and SN6h,
      defining different epitopes of EDG and developed a double-antibody sandwich assay
      to quantitate serum EDG in patients with solid tumors. SN6h possesses an
      exceedingly high antigen-binding avidity (K, 1.38 x 10(11) liters/mol), whereas
      SN6a possesses an ordinary avidity for a mAb directed to a cell surface antigen
      (K, 2.85 x 10(8) liters/mol). We measured serum samples from 101 patients with
      solid tumors (34 colorectal cancers, 16 breast cancers, and 51 other cancers), 8
      patients with benign diseases, and 31 healthy volunteers. The serum level of EDG
      was significantly elevated in the patients with metastatic cancers. The mean
      serum EDG in the 42 metastasis-negative patients was 34.0 +/- 26.8 ng/ml (median
      value, 27.9 ng/ml), whereas the value in the 59 metastasis-positive patients was
      63.8 +/- 72.5 ng/ml (median value, 37.2 ng/ml). The difference in EDG levels
      between the two groups was statistically significant (P = 0.012). Of the
      colorectal cancer patients, the difference in EDG levels between the 19
      metastasis-negative patients and the 15 metastasis-positive patients was
      statistically significant (P = 0.02). In addition, the difference between the
      normal control (n = 31) and the 15 metastasis-positive colorectal cancer patients
      was statistically significant (P = 0.04). Of the breast cancer patients, the
      difference in EDG levels between the 11 metastasis-positive patients and the
      normal control was statistically significant (P < 0.005). In additional studies,
      we found that chemotherapy suppressed serum EDG levels in cancer patients. Of the
      54 metastasis-positive patients with solid tumors, the mean serum EDG in the 32
      chemotherapy-receiving [chemotherapy(+)] patients was 44.7 +/- 41.9 ng/ml (median
      value, 36.1 ng/ml), whereas the value in the 22 chemotherapy(-) patients was
      102.4 +/- 99.5 ng/ml (median value, 64.8 ng/ml). The difference in serum EDG
      between the two groups is statistically significant (P < 0.005). In the majority
      of metastasis-positive patients who were not receiving chemotherapy, serum EDG
      was elevated. The results suggest that serum EDG may be a useful marker for
      monitoring early signs of metastasis and cancer relapse in a long-term follow-up
      of solid tumor patients.

PMID- 11297244
TI  - Microscopic analysis and significance of vascular architectural complexity in
      renal cell carcinoma.
AB  - The objective of this study was to evaluate the utility of measuring microvessel
      fractal dimension (MFD) as a parameter of architectural microvascular complexity
      in localized renal cell carcinoma (RCC). Forty-nine patients with low-stage clear
      cell RCC were assessed in a 9-year follow-up retrospective study. Tumor vessels
      were visualized with the endothelial marker CD34. Tumor microvessel density (MVD)
      was measured by computerized morphometry. Fractal analysis of the RCC
      microvascular network was performed and the MFD was computed in each case.
      Correlation between tumor vascular parameters, histological grade, extent of
      tumor necrosis and patient survival were tested by uni- and multivariate
      analyses. A significant correlation was found between tumor grade and decreased
      survival (P = 0.04). The extent of macroscopic tumor necrosis also significantly
      correlated with poor prognosis (P = 0.0001). Survival analysis revealed a
      significantly higher MVD in patients who survived longer than 5 years as compared
      with those who died before the end of the 5-year follow-up period (MVD = 10.8 +/-
      4.7% versus 6.4 +/- 3.7%; P = 0.03). MVD was also inversely associated with the
      extent of tumor necrosis (P = 0.03). Microvessel fractal dimension was
      significantly higher in low- as compared with high-grade tumors (1.55 +/- 0.11
      versus 1.45 +/- 0.15; P = 0.03). Survival analysis revealed a significantly
      higher MFD in those who lived >5 years as compared with those who died earlier
      (1.56 +/- 0.11 versus 1.46 +/- 0.15; P = 0.02). The MFD was inversely associated
      with the extent of tumor necrosis (P = 0.01). Multivariate analysis revealed that
      the MFD was the only significant factor to correlate with tumor necrosis, and
      that tumor necrosis was the only independent predictor of patient survival. These
      results indicate that the analysis of MFD as a marker of tumor microvascular
      complexity may provide important prognostic information as well as novel insight
      into the biology of tumor angiogenesis.

PMID- 11297245
TI  - Are basic fibroblast growth factor and vascular endothelial growth factor
      prognostic indicators in pediatric patients with malignant solid tumors?
AB  - Angiogenesis plays an important role in the growth, progression, and metastasis
      of solid tumors. Among angiogenic factors, basic fibroblast growth factor (bFGF)
      and vascular endothelial growth factor (VEGF) appear to be useful markers in
      adults with cancer. The aim of this pilot study was to determine the levels of
      VEGF in serum and bFGF in serum and urine of children with solid tumor at
      diagnosis (as measured by ELISA), and to investigate whether these parameters
      provide prognostic information. Forty consecutive patients with different types
      of cancer were prospectively included in this study. Median values of all studied
      angiogenic factors were higher in patients than in controls (n = 40), and the
      differences were statistically significant for bFGF in serum and urine: 10 versus
      3 pg/ml (P = 0.0004) and 6406 versus 0 pg/g of creatinine (P < 0.0001),
      respectively. Among patients, median serum values of bFGF and VEGF were higher in
      children with metastatic disease (n = 14) than in those with localized disease (n
      = 26). The difference was statistically significant for serum bFGF: 17.5 versus 6
      pg/ml (P = 0.02). Serum angiogenic factor levels correlated with outcome. The
      estimated event-free survival at 3 years was 79% for patients with normal bFGF
      values (n = 13) versus 42% (n = 26; P = 0.02) for those with high levels, and 71%
      in case of normal VEGF values (n = 20) versus 38% (n = 19; P = 0.04) for those
      with high levels. No benefit of normal urinary bFGF values was observed. Our
      results provide a rationale for exploring the clinical interest of bFGF and VEGF
      measurements in body fluids of a larger group of children with cancer.

PMID- 11297246
TI  - Overexpression of the cell cycle inhibitor p16INK4A in high-grade prostatic
      intraepithelial neoplasia predicts early relapse in prostate cancer patients.
AB  - Prostate cancer (PC) is the most commonly diagnosed male cancer in industrialized
      societies. No molecular markers of PC progression or outcome with proven clinical
      utility have been described. Because the loss of normal cell cycle control is an
      early event in the evolution of cancer, we sought to determine whether changes in
      expression of the cyclin-dependent kinase inhibitor, p16INK4A, predicted outcome
      in this disease. We screened a cohort of 206 patients with clinically localized
      PC treated with radical prostatectomy for overexpression of the INK4A gene, the
      product of which inactivates the G1-phase cyclin dependent kinases, Cdk4 and
      Cdk6. p16INK4A protein expression was evaluated by immunohistochemistry in areas
      of high-grade intraepithelial neoplasia (HGPIN), a precursor to invasive disease,
      and of cancer in the same specimen. Data were evaluated for disease relapse using
      the Kaplan-Meier method and in a Cox proportional hazards model by assessing
      p16INK4A status in areas of HGPIN and cancer with other variables of known
      clinical relevance. Overexpression of p16INK4A in HGPIN and cancer was correlated
      with, but independent of, pathological stage and was associated with early
      relapse in PC patients treated with radical prostatectomy (log-rank test, P <
      0.001). In a multivariate model adjusted for Gleason grade, pretreatment prostate
      specific antigen levels, pathological stage, and margin status, overexpression of
      p16INK4A in HGPIN was an independent predictor of disease relapse and increased
      the risk of recurrence 2.24-fold (95% confidence interval, 1.28-3.93). These data
      provide the first evidence for a prognostic marker in HGPIN. The clinical utility
      of p16INK4A status in stratifying patients for aggressive treatment very early in
      the disease process, potentially several years prior to the onset of invasive
      disease, requires further investigation.

PMID- 11297248
TI  - Overexpression of cyclooxygenase-2 in squamous cell carcinoma of the urinary
      bladder.
AB  - Epidemiological studies indicate that the development of squamous cell carcinoma
      of the urinary bladder is closely associated with chronic inflammation of the
      urinary tract, but the underlying mechanism is unknown. Cyclooxygenase (COX)-2 is
      involved in tumorigenesis in many tumors. The purpose of this study was to
      investigate the role of COX-2 in squamous cell carcinoma of the urinary bladder
      by immunoblot and immunohistochemical analyses. COX-2 protein was undetectable in
      normal bladder samples, but was expressed in 29 of 29 (100%) squamous cell
      carcinomas and in 8 of 8 (100%) squamous metaplasias. The expression of COX-2
      showed intense, homogenous cytoplasmic immunostaining in squamous cell
      carcinomas. In contrast, COX-2 was heterogeneously expressed in 6 of 12 (50%)
      cases of transitional cell carcinoma of the bladder combined with squamous cell
      carcinoma, consistent with previous findings. We provide the first evidence that
      COX-2 is expressed in squamous cell carcinomas of the urinary bladder and in the
      precursor lesions, indicating its involvement in the development of this type of
      malignancy.

PMID- 11297247
TI  - Ets-1 messenger RNA expression is a novel marker of poor survival in ovarian
      carcinoma.
AB  - Ets-1 proto-oncogene is a transcription factor involved in several cellular
      functions, including the activation of several proteases participating in tumor
      invasion and metastasis. The objective of this study was to analyze the possible
      correlation between Ets-1 mRNA expression and survival in advanced-stage ovarian
      carcinomas, studying two patient groups with extremely different disease outcome.
      Sections from 66 primary ovarian carcinomas and metastatic lesions from 41
      patients diagnosed with advanced-stage ovarian carcinoma (International
      Federation of Gynecologists and Obstetricians stages III and IV) were evaluated
      for expression of Ets-1 using mRNA in situ hybridization. Patients were divided
      into long-term (n = 17) and short-term (n = 24) survivors. The mean values for
      disease-free survival and overall survival were 116 and 133 months for long-term
      survivors, as compared to 3 and 21 months for short-term survivors, respectively.
      Expression of Ets-1 mRNA was detected in carcinoma cells and stromal cells in 28
      of 66 (42%) and 22 of 66 (33%) lesions, respectively. Ets-1 expression showed an
      association with mRNA expression of vascular endothelial growth factor (P = 0.001
      for carcinoma cells; P = 0.004 for stromal cells), basic fibroblast growth factor
      (P = 0.049 for carcinoma cells), and membrane type-1 matrix metalloproteinase (P
      = 0.045), which were previously studied in this patient cohort. Ets-1 mRNA was
      detected more often in both carcinoma and stromal cells in tumors of short-term
      survivors (P = 0.038 for carcinoma cells). In univariate survival analysis for
      all cases, Ets-1 expression in both tumor (P = 0.018) and stroma (P = 0.026)
      correlated with poor survival. These findings were reproduced in an analysis of
      primary tumors alone (P = 0.039 for tumor cells; P < 0.001 for stromal cells).
      Ets-1 mRNA expression in stromal cells retained its predictive power in a
      multivariate survival analysis in which all molecules studied previously in this
      patient cohort were included (P = 0.007). To our knowledge, this is the first
      evidence associating Ets-1 mRNA expression and poor survival in human epithelial
      malignancy. Ets-1 is thus a novel prognostic marker in advanced-stage ovarian
      carcinoma. The association between Ets-1 mRNA expression and the expression of
      membrane type-1 matrix metalloproteinase and angiogenic genes, first documented
      here in a study of patient material, points to the central role of this
      transcription factor in tumor progression in ovarian carcinoma.

PMID- 11297249
TI  - The prognostic value of molecular marker analysis in patients treated with
      trimodality therapy for esophageal cancer.
AB  - The purpose of this study was to define the prognostic value of a group of
      molecular tumor markers in a well-staged population of patients treated with
      trimodality therapy for esophageal cancer. The original pretreatment paraffin
      embedded endoscopic esophageal tumor biopsy material was obtained from 118
      patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy
      radiation followed by resection from 1986 until 1997 at the Duke University
      Comprehensive Cancer Center. Three markers of possible platinum chemotherapy
      association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P
      glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU
      association [thymidylate synthase (TS)] were measured using immunohistochemistry.
      The median cancer-free survival was 25.0 months, with a significantly improved
      survival for the 38 patients who had a complete response (P < 0.001). High-level
      expression of GST-pi, P-gp, and TS were associated with a decreased survival. MT
      was not significant in this population. Multivariate analysis identified high
      level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU
      marker TS as independent predictors of early recurrence and death. In conclusion,
      this investigation measured three possible markers associated with platinum and
      one possible marker associated with 5-FU in a cohort of esophageal cancer
      patients. Independent prognostic significance was observed, which suggests that
      it may be possible to predict which patients may benefit most from trimodality
      therapy. These data need to be reproduced in a prospective investigation.

PMID- 11297250
TI  - Expression of tissue factor pathway inhibitor 2 inversely correlates during the
      progression of human gliomas.
AB  - Protease inhibitors regulate a variety of physiological and pathological
      processes including angiogenesis, embryo implantation, intravascular
      fibrinolysis, wound healing, and tumor invasion. Tissue factor pathway inhibitor
      (TFPI) 2 is a Mr 32,000 Kunitz-type serine protease inhibitor that inhibits
      plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not
      urokinase-type plasminogen activator, tissue plasminogen activator, or thrombin.
      In this study, we determined the relative amounts of TFPI-2 in low-, intermediate
      , and high-grade human glioma cell lines and tumor tissue samples. TFPI-2 protein
      and mRNA levels (measured by Western and Northern blotting) were highest in low
      grade glioma cells (Hs683), lower in anaplastic astrocytoma cells (SW1088 and
      SW1783), and undetectable in high-grade glioma cells (SNB19). Analysis of TFPI-2
      protein in human normal brain and in glioma tumor tissues for TFPI-2 revealed the
      highest levels in normal brain, lesser amounts in low-grade gliomas and
      anaplastic astrocytomas, and undetectable amounts in glioblastomas. In situ
      hybridization of TFPI-2 mRNA with normal brain tissues revealed the greatest
      positivity in neurons, with moderate positivity in both glial and endothelial
      cells and moderate, little, or no TFPI-2 mRNA in low-grade glioma, anaplastic
      astrocytoma, and glioblastoma tumor tissue samples, respectively. We also found
      that recombinant TFPI-2 inhibited the invasiveness of SNB19 glioblastoma cells in
      a Matrigel assay in a dose-dependent manner. Collectively, these results suggest
      that TFPI-2 has a regulatory role in the invasiveness of gliomas in vitro and in
      vivo.

PMID- 11297251
TI  - Detection of epidermal growth factor receptor mRNA in peripheral blood: a new
      marker of circulating neoplastic cells in bladder cancer patients.
AB  - Despite the large number of studies performed in solid tumors, few attempts at
      molecular detection of urothelial cells in blood have been made. Specifically,
      only uroplakin II (UP-II) and cytokeratin 20 (CK-20) have been suggested as tumor
      markers in the blood of bladder cancer patients. Epidermal growth factor receptor
      (EGFR) mRNA expression was found in the blood of patients with some types of
      carcinoma; nevertheless, its expression has been never investigated in the blood
      of patients with urothelial tumors. We used a EGFR-based reverse transcription
      PCR assay for the detection of tumoral cells in the blood of 27 patients with
      bladder cancer, in 30 healthy donors, and in 9 patients with cystitis. EGFR
      expression was compared with that of known markers of circulating epithelial
      cells, CK-19 and CK-20, and to a urothelial-specific marker, UP-II. Analysis by
      reverse transcription-PCR and Southern blot hybridization showed no evidence of
      EGFR and UP-II mRNA expression in any of the samples used as controls. Analysis
      of healthy donors showed mRNA expression for CK-19 and CK-20 in 6 of 30 and in 4
      of 30 samples, respectively. All patients with cystitis resulted negative for
      EGFR expression, whereas 3 of 9, 2 of 9, and 3 of 9 were found expressing CK-19,
      CK-20, and UP-II, respectively. Among blood samples from tumoral patients, 74%
      had EGFR mRNA and 41% had positive signals for CK-19, whereas positivity for CK
      20 and UP-II was found in 15% and 37% of patients, respectively. These results
      seem to indicate that EGFR mRNA in the blood may be a useful tumor marker in
      bladder cancer patients, as well as in other patients with epithelial tumors.

PMID- 11297252
TI  - Aberrant methylation during cervical carcinogenesis.
AB  - We studied the pattern of aberrant methylation during the multistage pathogenesis
      of cervical cancers. We analyzed a total of 73 patient samples and 10 cervical
      cancer cell lines. In addition, tissue samples [peripheral blood lymphocytes (n =
      10) and buccal epithelial cells (n = 12)] were obtained from 22 healthy
      volunteers. On the basis of the results of preliminary analysis, the cervical
      samples were grouped into three categories: (a) nondysplasia/low-grade cervical
      intraepithelial neoplasia (CIN; n = 37); (b) high-grade CIN (n = 17); and (c)
      invasive cancer (n = 19). The methylation status of six genes was determined
      (p16, RARbeta, FHIT, GSTP1, MGMT, and hMLH1). Our main findings are as follows:
      (a) methylation was completely absent in control tissues; (b) the frequencies of
      methylation for all of the genes except hMLH1 were >20% in cervical cancers; (c)
      aberrant methylation commenced early during multistage pathogenesis and
      methylation of at least one gene was noted in 30% of the nondysplasia/low-grade
      CIN group; (d) an increasing trend for methylation was seen with increasing
      pathological change; (e) methylation of RARbeta and GSTP1 were early events, p16
      and MGMT methylation were intermediate events, and FHIT methylation was a late,
      tumor-associated event; and (f) methylation occurred independently of other risk
      factors including papillomavirus infection, smoking history, or hormone use.
      Although our findings need to be extended to a larger series, they suggest that
      the pattern of aberrant methylation in women with or without dysplasia may help
      identify subgroups at increased risk for histological progression or cancer
      development.

PMID- 11297253
TI  - Multiple detection of genetic alterations in tumors and stool.
AB  - Detection of genetic alterations in exfoliated intestinal cells in stool could
      represent an alternative, noninvasive tool for the screening of colorectal
      tumors. To verify this, we analyzed p53 and K-ras mutations and microsatellite
      instability on 46 cases of colorectal cancer and compared the presence of
      molecular alterations in tumor tissue and stool samples from individual patients.
      p53 exons 5-8 and K-ras exons 1-2 were analyzed by denaturing gradient gel
      electrophoresis. For the microsatellite instability, a set of 5 microsatellite
      markers (D2S123, D5S346, D17S250, BAT25, and BAT26) was evaluated. In the 18
      healthy individuals, no genetic alterations in either tissue or stool were
      detected. p53 mutations were detected in 17 (37%), K-ras alterations in 15 (33%),
      and microsatellite instabilities in 5 (11%) of the 46 tumors analyzed. In a side
      study, we analyzed the correlation in genetic alteration profiles between tumors
      and macroscopically normal or healthy tissue from the same patient. The presence
      of at least one molecular alteration in tumor was observed in 31 (67%) of the
      cases. p53, K-ras mutations, and microsatellite instabilities were detected in
      stool samples in 18, 40, and 60% of patients with tumors harboring the same
      alterations. Due to the largely complementary presence of p53 and K-ras mutations
      in tumors, the use of highly sensitive procedures for stool analysis could offer
      a means competitive with colonoscopy and the fecal occult blood test.

PMID- 11297254
TI  - Frequent down-regulation of E-cadherin by genetic and epigenetic changes in the
      malignant progression of hepatocellular carcinomas.
AB  - E-cadherin mediates cell-cell adhesion by associating with catenins. Loss of E
      cadherin function by genetic or epigenetic alteration of the E-cadherin gene
      (CDH1) leads to tumorigenesis. To study the involvement of E-cadherin dysfunction
      in liver tumorigenesis, we examined the allelic loss and methylation of 5'-CpG
      sites of CDH1 in hepatocellular carcinomas (HCCs). Loss of heterozygosity (LOH)
      of CDH1 and adjacent 16q22-23 loci was observed in 13 of 30 (43%) HCCs.
      Methylation of the 5'-CpG of CDH1 was analyzed by Southern blot hybridization,
      and hypermethylation was observed in 8 of the 24 (33%) HCCs examined. The amount
      of E-cadherin mRNA was analyzed by RNase protection assay, and a decrease in E
      cadherin mRNA was observed in 10 of the 23 cases examined. A reduction in E
      cadherin was found in 10 of 21 HCCs using immunoblot analysis. The amount of E
      cadherin was comparable to that of E-cadherin mRNA. Down-regulation of E-cadherin
      was common in cases with LOH but rare in cases with methylated promoter. These
      results suggest that hypermethylation of the CDH1 promoter is present in a small
      cell population in the tumor, thus the methylation status is liable to vary
      according to individual cell condition. Hypermethylation was observed in early
      stage HCCs, whereas LOH was found frequently in more malignant tumors. Down
      regulation of E-cadherin is closely related to the progression of HCCs and is
      stably induced by LOH of CDH1.

PMID- 11297255
TI  - Detection of p53 gene mutations in human esophageal squamous cell carcinomas
      using a p53 yeast functional assay: possible difference in esophageal
      carcinogenesis between the young and the elderly group.
AB  - A p53 yeast functional assay, which cannot only detect p53 gene mutations but
      also can assess p53 gene function, was used to screen for p53 gene dysfunction in
      human esophageal squamous cell carcinomas. Surgically resected frozen tissues of
      esophageal squamous cell carcinomas from 57 patients were examined for p53 gene
      mutation. Because the mean age of the patients diagnosed with esophageal squamous
      cell carcinoma was 64 years, we classified those who were <65 years of age as the
      Young Group and classified the others as the Elderly Group. The incidence of p53
      gene mutations was 43 of 57 (75%). The incidence of p53 gene mutations observed
      in the Young Group was significantly higher than in the Elderly Group (P =
      0.0007). Alcohol and smoking status did not relate to p53 gene mutation
      expression. Survival rate after surgery was not significantly associated with the
      presence of p53 gene mutation. However, in the Young Group with p53 gene
      mutation, those who had null mutations had a significantly shorter survival than
      those without null mutations (P = 0.0455). No other clinicopathological factors
      were associated with p53 gene mutations. Possibly, there may be a difference in
      esophageal carcinogenesis between the Young and the Elderly groups, because the
      incidence of p53 gene mutations is different between the two groups. In the Young
      Group, p53 gene mutation may cause esophageal carcinogenesis, and null mutation
      for p53 gene is a significant prognostic factor.

PMID- 11297256
TI  - Detection of head and neck squamous cell carcinoma among exfoliated oral mucosal
      cells by microsatellite analysis.
AB  - Prompt detection of head and neck squamous cell carcinoma (HNSCC) is vital to
      successful patient management. In this feasibility study, we used microsatellite
      analysis to detect tumor-specific genetic alterations in exfoliated oral mucosal
      cell samples from patients with known cancer. Exfoliated mucosal cells in
      pretreatment oral rinse and swab samples were collected from 44 HNSCC patients
      and from 43 healthy control subjects (20 nonsmokers and 23 smokers). We tested a
      panel of 23 informative microsatellite markers to assay DNA from the matched
      lymphocyte, tumor (from cancer cases), and oral test samples. Loss of
      heterozygosity or microsatellite instability of at least one marker was detected
      in 38 (86%) of 44 primary tumors. Identical alterations were found in the saliva
      samples in 35 of these 38 cases (92% of those with markers; 79% overall)
      including 12 of 13 cases with small primaries [stage Tt or Tx (occult primary)]
      and 4 of 4 cases of patients that had undergone prior radiation. Microsatellite
      instability was detectable in the saliva in 24 (96%) of 25 cases in which it was
      present in the tumor, and loss of heterozygosity was identified in the test
      sample in 19 (61%) of 31 cases. No microsatellite alterations were detected in
      any of the samples from the healthy control subjects. This approach must now be
      refined and validated for the detection of clinically occult disease.
      Microsatellite analysis of oral samples may then become a valuable method for
      detecting and monitoring HNSCC.

PMID- 11297257
TI  - O6-Methylguanine-DNA methyltransferase in pediatric primary brain tumors:
      relation to patient and tumor characteristics.
AB  - The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) confers
      resistance to methylating and chloroethylating agents in pediatric
      medulloblastoma- and glioma-derived cell lines and xenografts. Here, we assayed
      MGMT activity in 110 pediatric brain tumors to establish correlates with patient
      and tumor characteristics. We also assayed MGMT in histologically normal brain
      adjacent to 22 tumors to characterize changes in activity accompanying
      neurocarcinogenesis. MGMT activity was detected in 94% of tumors, ranging ca.
      1,500-fold from 0.34 to 498 fmol/10(6) cells (approximately 205-300,000
      molecules/cell). Mean activity was 25 +/- 66 fmol/10(6) cells, including six
      specimens with undetectable activity (Mer- phenotype; <0.25 fmol/10(6) cells or
      151 molecules/cell). MGMT content varied 10-fold among diagnostic groups and was
      associated with degree of malignancy, as evidenced by a 4-fold difference in
      activity between high- and low-grade tumors (P = 0.03). Tumor MGMT content was
      age dependent, being 5-fold higher in children 3-12 years old than in infants (P
      = 0.015) and adolescents (P = 0.015). Mean activity in tumors was 9-fold higher
      than in adjacent histologically normal brain (21 +/- 44 versus 2.4 +/- 4.0
      fmol/10(6) cells; P = 0.05). By comparing tumor and adjacent normal tissue from
      the same patient, we found that 68% of cases exhibited an elevation of tumor
      activity that ranged from 2- to >590-fold. Moreover, 67% of Mer- normal tissue
      was accompanied by Mer+ tumor. These observations indicate that MGMT activity is
      frequently elevated during pediatric neurocarcinogenesis. Significantly, enhanced
      MGMT activity may heighten resistance to alkylating agents, suggesting a
      potential role for MGMT inhibitors in therapy.

PMID- 11297258
TI  - Screening for and identification of novel agents directed at renal cell
      carcinoma.
AB  - We were interested in identifying novel agents for renal cell carcinoma (RCC) by
      screening for activities that model renal tumor biology. Searching for relative
      renal cell sensitivity and leukemia insensitivity among cytotoxicity profiles in
      the NCI Drug Screen database, we identified 16 potential agents with renal
      selectivity. We evaluated the agents in 10 RCC cell lines (of primary and
      metastatic origin) isolated from 5 patients. The 50% inhibitory concentrations
      (IC50) in these cell lines ranged from 0.019 +/- 0.013 to 11.4 +/- 0.55 microM
      and were comparable with values obtained with renal cell lines in the NCI Drug
      Screen panel. Because RCC are slowly growing tumors, we evaluated the compounds
      on rapidly (27% S phase) or slowly (6% S phase) growing cells. In contrast to
      doxorubicin, where cytotoxicity was restricted to rapidly proliferating cells,
      three compounds (NSC 280074, 281613, and 281817) were more cytotoxic in slowly
      proliferating cells. NSC 72151 and 268965 were equitoxic for both populations.
      NSC 94889, 638850, and 630938 were more cytotoxic in rapidly growing cells. In in
      vitro time exposure studies, four compounds, NSC 268965, 280074, 281613, and
      281817, were maximally cytotoxic with as little as 3 h exposure time. From an
      analysis comparing the p53 genotype of the 60 cell lines of the National Cancer
      Institute (NCI) Drug Screen with the cytotoxicity profiles for the 16 putative
      renal compounds, 13 compounds were classified as likely to be indifferent to p53
      status. We also developed a panel specificity detection method for the NCI Drug
      Screen database to evaluate the prevalence of renal sensitive compounds. Of the
      16 studied compounds, 14 were among those identified as renal sensitive by the
      statistical analysis. Lastly, we found reduced tumor growth in mice with
      established renal human tumor xenografts after treatment with two of the renal
      active compounds. These studies describe compounds with potential renal activity
      that are candidates for preclinical development for renal cell carcinoma.

PMID- 11297259
TI  - Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human
      T98G glioblastoma multiforme xenografts.
AB  - Although rare, the morbidity and mortality from brain tumors are significant.
      Chemotherapy has made only a small impact on these tumors. The human T98G
      glioblastoma multiforme cell line was used as a brain tumor model. The protein
      kinase Cbeta inhibitor 317615 x 2HCl was not highly cytotoxic toward T98G cells
      in culture and was additive in cytotoxicity with carmustine (BCNU). When nude
      mice bearing s.c. T98G tumors were treated with 317615 x 2HCl p.o. twice daily on
      days 14-30 after tumor cell implantation, the number of intratumoral vessels
      stained by CD31 was decreased to 37% of control, and the number of intratumoral
      vessels stained by CD105 was decreased to 50% of control. The compound 317615 x
      2HCl was an active antitumor agent against s.c. growing T98G xenografts. A
      treatment regimen administering 317615 x 2HCl before, during, and after BCNU was
      compared with a treatment regimen administering 317615 x 2HCl sequentially after
      BCNU. In the tumor growth delay determination of the s.c. tumor, the sequential
      treatment regimen was more effective than the simultaneous treatment regimen.
      However, when the same treatments were administered to animals bearing
      intracranial T98G tumors, the survival of animals receiving the simultaneous
      treatment regimen increased from 41 days for those treated with BCNU alone to 102
      days for animals treated with the combination, whereas animals receiving the
      sequential treatment regimen survived 74 days. Treatment with the protein kinase
      Cbeta inhibitor decreased T98G glioblastoma multiforme angiogenesis and improved
      treatment outcome with BCNU.

PMID- 11297260
TI  - Combined targeting of adenoviruses to integrins and epidermal growth factor
      receptors increases gene transfer into primary glioma cells and spheroids.
AB  - Adenoviral-mediated gene transfer is suboptimal in human glioma and limits in
      vivo gene therapy approaches. There is a need for targeted vectors able to
      enhance gene transfer into the tumor as well as to lower the viral load in the
      surrounding normal tissues. We evaluated primary human tumor samples by
      immunohistochemistry and fluorescence-activated cell sorter for expression of the
      Coxsackie-adenovirus receptor and other antigens with potential utility to
      redirect adenoviruses (Ads) to gliomas. In the majority of the samples, Coxsackie
      adenovirus receptor expression was low. This correlated with inefficient gene
      transfer in vitro. Epidermal growth factor receptor (EGFR) and alpha(v)beta5
      integrins were often highly, but heterogeneously, expressed. We hypothesized that
      these receptors, overexpressed in tumor but not in normal brain, could serve as
      independent binding sites for alternative pathways of infection with targeted
      Ads. We examined this, using Ads that expressed the luciferase reporter gene
      under the cytomegalovirus promoter. Targeting to the EGFR was performed with a
      single-chain bispecific antibody directed against the human EGFR and against the
      fiber knob of the Ad. Targeting to the alpha(v) integrins was performed by
      insertion of an integrin-binding sequence, RGD-4C, in the HI-loop of the Ad.
      Increased luciferase gene transfer in primary glioma cells was observed in 8 of
      13 samples with EGFR-targeting (2-11 times enhancement; median, 6) and in all of
      the samples with RGD-targeting (2-42 times enhancement; median, 12). Combining
      the two targeting motifs further enhanced the gene transfer in primary glioma
      cells in an additive manner (3-56 times; median, 20). The double-targeted Ads
      also strongly augmented gene transfer into organotypic glioma spheroids.
      Conversely, gene transfer into normal brain explants was reduced dramatically
      using Ads targeted to the tumor. Our findings demonstrate the feasibility and
      benefit of binding multiple ligands to the adenoviral fiber knob. These vectors
      have a great potential for clinical use in the context of tumors that are usually
      heterogeneous for target antigen expression at the single-cell level.

PMID- 11297261
TI  - Photodynamic therapy in the canine prostate using motexafin lutetium.
AB  - Our purpose was to determine the feasibility of comprehensive treatment of the
      canine prostate with photodynamic therapy (PDT) using motexafin lutetium (Lu-Tex)
      and to evaluate the toxicity and tissue effects associated with this treatment.
      Twenty-five adult male beagles with normal prostate glands were given an i.v.
      injection of the second-generation photosensitizer Lu-Tex (2-6 mg/kg). An
      additional two dogs were used as controls and did not receive any
      photosensitizing drug. All 27 dogs underwent laparotomy to expose the prostate.
      Three hours postinjection, a total dose of 75-150 J/cm of 732 nm laser light was
      delivered interstitially and/or transurethrally to the prostate via cylindrical
      diffusing fibers. Dogs were euthanized between 2 days and 3 months after PDT. All
      subjects were monitored for clinical evidence of toxicity. Specimens were
      examined macroscopically and microscopically to characterize the tissue reaction
      and assess extent of tissue effect as a result of treatment. Interstitial and/or
      transurethral PDT were successfully delivered in all dogs with no perioperative
      complications. No clinical evidence of acute urinary obstruction or rectal
      bleeding was noted. At all dose levels, macroscopic and microscopic evaluation
      revealed a prostatic tissue reaction characterized initially (within 48 h) by
      inflammation and necrosis followed by fibrosis and glandular epithelial atrophy.
      Comprehensive treatment of the entire prostate could be achieved using the
      interstitial alone approach or combined transurethral and interstitial approach.
      The transurethral alone approach did not result in complete coverage of the
      prostate. Dogs receiving transurethral or combined interstitial and transurethral
      treatment developed erythema and urethral epithelial disruption at all dose
      levels. Those receiving combined treatment at the highest dose level (Lu-Tex 6
      mg/kg, 150 J/cm light) developed urethral fistulae and peritonitis. Dogs treated
      with the interstitial alone approach were found to have the least amount of
      urethral damage. Comprehensive treatment of the canine prostate with Lu-Tex PDT
      is feasible using an interstitial alone or combined interstitial and
      transurethral approach. The interstitial alone technique results in the least
      amount of toxicity. The prostatic tissue reaction to treatment is characterized
      by initial inflammation and necrosis followed by fibrosis and glandular
      epithelial atrophy.

PMID- 11297262
TI  - Down-regulation of galectin-3 suppresses tumorigenicity of human breast carcinoma
      cells.
AB  - Galectin-3 is an endogenous beta-galactoside-binding protein with specificity for
      type I and II ABH blood group epitopes and poly-N-acetyllactosamine glycan
      containing cell surface glycoproteins and is the major nonintegrin cellular
      laminin-binding protein. Galectin-3 is expressed at an elevated level in a wide
      range of neoplasms, and expression was shown to be associated in some tumor cell
      systems with metastases. Here we determined the functional consequence of
      blocking galectin-3 expression in highly malignant human breast carcinoma MDA-MB
      435 cells. Inhibition of galectin-3 expression led to reversion of the
      transformed phenotype as determined by altered morphology, loss of serum
      independent growth, acquisition of growth inhibition properties by cell contact,
      and abrogation of anchorage-independent growth. The blockage of galectin-3
      expression led to a significant suppression of tumor growth in nude mice. These
      results provide direct evidence that galectin-3 expression is necessary for the
      maintenance of the transformed and tumorigenic phenotype of MDA-MB-435 breast
      carcinoma cells.

PMID- 11297264
TI  - Involvement of microsomal cytochrome P450 and cytosolic thymidine phosphorylase
      in 5-fluorouracil formation from tegafur in human liver.
AB  - Recently, we have reported that tegafur, an anticancer agent, is biotransformed
      into active drug 5-fluorouracil (5-FU) by cytochromes P450 1A2, 2A6, and 2C8 in
      human liver microsomes (T. Komatsu et al., Drug Metab. Dispos, 28: 1457-1463,
      2000). Because the conversion of tegafur into 5-FU has also been reported to be
      catalyzed by cytosolic thymidine phosphorylase (dThdPase), the involvement of
      human liver microsomes and cytosol and individual differences in 5-FU formation
      from tegafur were investigated. In 14 human samples, the mean rates of 5-FU
      formation in liver microsomes were 5-fold and 2-fold higher than those in liver
      cytosol at substrate concentrations of 100 microM and 1 mM tegafur, respectively.
      In the presence of 5-chloro-2,4-dihydroxypyridine, a dihydropyrimidine
      dehydrogenase inhibitor, the rates of 5-FU formation by the combination of liver
      microsomes and cytosol showed 5- and 3-fold interindividual differences at 100
      microM and 1 mM tegafur, respectively. Kinetic analysis of human liver cytosolic
      5-FU formation indicated an apparent higher Km value (16 +/- 4 mM) than that of
      liver microsomes (1.8 +/- 0.3 mM) with similar Vmax values. Human liver cytosolic
      5-FU formation was confirmed to be catalyzed by dThdPase with correlation and
      chemical inhibition studies. These results suggested that 5-FU formation from
      tegafur in human liver was mainly catalyzed by microsomal P450 at low
      concentrations of tegafur, but the contribution of cytosolic 5-FU formation by
      dThdPase would be important at high concentrations.

PMID- 11297263
TI  - UCN-01 suppresses E2F-1 mediated by ubiquitin-proteasome-dependent degradation.
AB  - E2F-1 regulates the transcription of genes required for DNA synthesis.
      Previously, we have reported that UCN-01 suppresses E2F-1 protein expression
      without any noticeable effect on its mRNA level in gastric cancer cell line SK
      GT5 (Clin. Cancer Res., 4: 2201-2206, 1998). In this study, we investigated the
      mechanism responsible for the suppression of E2F-1 expression by UCN-01 in SK-GT5
      cells. After 24-h exposure to 1 microM UCN-01, E2F-1 protein expression was
      decreased by >99%. The suppressive effect of UCN-01 could be reversed by
      ubiquitin-dependent proteasome inhibitors such as calpain inhibitor I and
      lactacystin. Transfection experiments using expression plasmids encoding full
      length E2F-1 or truncated E2F-1 with deletion of the COOH-terminal region (which
      is required for eliciting ubiquitination and protein degradation) revealed that
      the expression of truncated E2F-1 was not affected by UCN-01. Other cell-cycle
      related and ubiquitin-proteasome-regulated proteins such as p21, p27, and cyclin
      B1 were not repressed by UCN-01 in E2F-1-overexpressing cells. In vitro
      translated, full-length E2F-1 degraded more rapidly upon incubation with extracts
      from UCN-01-treated cells when compared with truncated E2F-1. Taken together,
      these data indicate that UCN-01 suppresses E2F-1 protein expression mediated by
      the ubiquitin-proteasome pathway in a specific manner.

PMID- 11297266
TI  - Growth-inhibitory effects of CD40 ligand (CD154) and its endogenous expression in
      human breast cancer.
AB  - CD40 binding produces multifaceted growth signals in normal and malignant B
      cells, whereas its physiological role is less well characterized in epithelial
      cancers. We examined the growth outcome of CD40 ligation in human breast cancer
      cells, using CD40+ (T47D and BT-20) and CD40-negative (MCF-7, ZR-75-1) cell lines
      as defined by flow cytometric analysis, immunohistochemistry, and reverse
      transcription-PCR. Treatment with the soluble recombinant CD40 ligand (CD40L)
      molecules gp39 or CD40L-trimer significantly reduced [3H]thymidine uptake in BT
      20 and T47D cells by up to 40%, but did not affect the growth of CD40-negative
      MCF-7 or ZR-75-1 cells. Similarly, significant growth inhibition was observed
      after co-incubation with CD40L-transfected murine L cells (55.0 +/- 8.9%, P <
      0.001) that express membrane CD40L constitutively, or with paraformaldehyde
      fixed, CD3+ CD40L+ PBLs from three different HLA-mismatched donors (39.7 +/-
      3.7%, P < 0.01). Untransfected L cells and non-CD40L-expressing lymphocytes did
      not produce significant growth inhibition. The in vivo antitumorigenic effects of
      CD40L were examined using a s.c. severe combined immunodeficient-hu xenograft
      model. Pretreatment with two different soluble recombinant CD40L constructs
      (CD40L and gp39) produced similar xenograft growth-inhibitory effects [67 +/- 24%
      (n = 4), and 65 +/- 14% (n = 8) inhibition, respectively], which were reversed by
      co-treatment with the CD40L-neutralizing antibody LL48. In vitro analysis
      indicated that CD40L-induced growth inhibition was accompanied by apoptotic
      events including cell shrinkage, rounding, and detachment from the adherent T47D
      culture monolayer. Thirty-one and 27% of gp39-treated T47D and BT-20 cells
      underwent apoptosis, respectively, as compared with 56 and 65% from the same cell
      lines after treatment with the Fas agonistic antibody CH-11. An up-regulation of
      the proapoptotic protein Bax in T47D and BT-20 cells was observed, which
      indicated that this Bcl-2 family member may contribute to this growth-inhibitory
      effect. To explore the clinical relevance of CD40L-CD40 interaction,
      retrospective immunohistochemical analysis was carried to characterize in situ
      CD40- and CD40L-expression in breast cancer patient biopsies. All of the
      infiltrating ductal (5 of 5 cases tested) and lobular (4 of 4 cases) breast
      carcinomas, carcinomas in situ (6 of 6 cases), and mucinous carcinoma tested (1
      case) expressed CD40. Varying proportions of tumor cells also expressed CD40L in
      the majority of infiltrating ductal (3 of 5 cases) and lobular (3 of 4 cases)
      carcinomas, and carcinomas in situ (4 of 6 cases), as determined by
      immunohistochemistry and validated by RT-PCR detection of the CD40L message in
      only CD40L positive-staining cases. Tumor infiltrating mononuclear cells from
      infiltrating carcinomas and carcinomas in situ expressed CD40 (10 of 10 cases),
      but less commonly CD40L (1 case of infiltrating lobular carcinoma, 2 cases of
      carcinoma in situ). Our findings indicate that the CD40 signaling pathway is
      active in human breast carcinoma cells. However, tumor-infiltrating lymphocytes
      from primary tumor tissues may be limited in their capacity to directly modulate
      tumor growth through the CD40L-CD40 loop.

PMID- 11297265
TI  - Radiosensitization of malignant glioma cells through overexpression of dominant
      negative epidermal growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in neoplastic
      growth control of malignant gliomas. We have demonstrated that radiation
      activates EGFR Tyr-phosphorylation (EGFR Tyr-P) and the proliferation of
      surviving human carcinoma cells, a likely mechanism of accelerated cellular
      repopulation, a major cytoprotective response after radiation. We now investigate
      the importance of radiation-induced activation of EGFR on the radiosensitivity of
      the human malignant glioma cells U-87 MG and U-373 MG. The function of EGFR was
      inhibited through a genetic approach of transducing cells with an Adenovirus (Ad)
      vector containing dominant-negative (DN) EGFR-CD533 (Ad-EGFR-CD533) at
      efficiencies of 85-90%. The resulting cells are referred to as U-87-EGFR-CD533
      and U-373-EGFR-CD533. After irradiation at 2 Gy, both of the cell lines exhibited
      a mean 3-fold increase in EGFR Tyr-P. The expression of EGFR-CD533 completely
      inhibited the radiation-induced activation of EGFR. In clonogenic survival assays
      after a single radiation exposure, the radiation dose for a survival of 37% (D37)
      for U-87-EGFR-CD533 cells was 1.4- to 1.5-fold lower, relative to cells
      transduced with AdLacZ or untransduced U-87 MG cells. This effect was amplified
      with repeated radiation exposures (3 x 2 Gy) yielding a D37 ratio of 1.8-2.0. In
      clonogenic survival studies with U-373 MG cells, the radiosensitizing effect of
      EGFR-CD533 was similar. Furthermore, in vivo studies with U-87 MG xenografts
      confirmed the effect of EGFR-CD533 on tumor radiosensitization (dose enhancement
      ratio, 1.8). We conclude that inhibition of EGFR function via Ad-mediated gene
      transfer of EGFR-CD533 results in significant radiosensitization. As underlying
      mechanism, we suggest the disruption of a major cytoprotective response involving
      EGFR and its downstream effectors, such as mitogen-activated protein kinase. The
      experiments demonstrate for the first time that radiosensitization of malignant
      glioma cells through disruption of EGFR function may be achieved by genetic
      therapy approaches.

PMID- 11297267
TI  - Antitumor effects of a novel phenoxazine derivative on human leukemia cell lines
      in vitro and in vivo.
AB  - 2-Amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx) was
      synthesized by reacting 2-amino-5-methylphenol with bovine hemolysates. Because
      Phx is a phenoxazine derivative like actinomycin D, we examined its effects on
      the proliferation of the human leukemia cell lines K562, HL-60, and HAL-01. Phx
      inhibited proliferation and induced apoptosis in all of the leukemia cell lines
      we tested, in a dose-dependent manner. We further investigated the antitumor
      effect of this compound on HAL-01-bearing nude mice. Treatment with Phx markedly
      reduced the tumor growth rate in the experimental group, as compared with the
      control group. Moreover, Phx was found to have few adverse effects on weight loss
      and WBC count. In addition, we examined the effects of Phx on human normal
      hematopoietic progenitor cells by a clonogenic assay, and we observed less
      suppression of normal progenitor cells than of leukemic progenitors. These
      results suggest that Phx may be used to treat patients affected by different
      types of leukemia.

PMID- 11297268
TI  - Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and
      sensitization of B-cell non-Hodgkin's lymphoma to apoptosis.
AB  - Treatment of patients with non-Hodgkin's lymphoma (NHL) is frequently hampered by
      development of chemoresistance. Rituximab is a chimeric mouse antihuman CD20
      antibody that offers an alternative; however, its mechanism of action is not
      clearly understood. Treatment of lymphoma cell lines with Rituximab sensitizes
      the cells to the cytotoxic and apoptotic effects of therapeutic drugs, e.g.,
      cisplatin, fludarabine, vinblastine, and Adriamycin. This study investigated the
      mechanism(s) involved in the reversal of drug resistance by Rituximab therapy.
      NHL cells synthesize and secrete antiapoptotic cytokines implicated in drug
      resistance, including interleukin (IL)-6, IL-10, and tumor necrosis factor alpha.
      We hypothesized, therefore, that sensitization by Rituximab may be due in part to
      modification of cytokine production. In this study, examination of cytokine
      secretion by NHL 2F7 tumor cells revealed down-regulation of IL-10 by Rituximab
      treatment. Moreover, cytotoxicity assays using exogenous IL-10 and IL-10
      neutralizing antibodies demonstrated that IL-10 serves as an
      antiapoptotic/protective factor in these tumor cells against cytotoxic drugs.
      Furthermore, expression in 2F7 cells of the protective factor, Bcl-2, was shown
      to be dependent on IL-10 levels and down-regulated by Rituximab. Other gene
      products such as Bax, Bcl-x, Bad, p53, c-myc, and latent membrane protein-1 (LMP)
      were not affected by Rituximab treatment. Drug sensitization, as well as down
      regulation of both IL-10 and Bcl-2, was corroborated in experiments using the NHL
      cell line 10C9. The Ramos and Daudi NHL cell lines were not sensitizable, nor did
      their Bcl-2 or IL-10 levels change. These studies demonstrate that one mechanism
      by which Rituximab sensitizes NHL to chemotherapeutic drugs is mediated through
      down-regulation of antiapoptotic IL-10 autocrine/paracrine loops and Bcl-2. The
      clinical relevance of these findings is discussed.

PMID- 11297269
TI  - Squalamine treatment of human tumors in nu/nu mice enhances platinum-based
      chemotherapies.
AB  - Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II
      clinical trials in cancer patients. To broaden our understanding of the clinical
      potential for squalamine, this agent was evaluated in nu/nu mouse xenograft
      models using the chemoresistant MV-522 human non-small cell lung carcinoma and
      the SD human neuroblastoma lines. Squalamine was studied alone and in combination
      with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a
      modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that
      was better than cisplatin alone. Squalamine also significantly enhanced the
      activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model.
      Squalamine similarly improved the effectiveness of cisplatin in producing TGI
      when screened against the SD human neuroblastoma xenograft. Xenograft tumor
      shrinkage was seen for the MV-522 tumor in combination treatments including
      squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from
      the treatment regimen. To gain a greater understanding of the mechanism by which
      squalamine inhibited tumor growth in the xenograft studies, in vitro experiments
      were carried out with vascular endothelial growth factor-stimulated human
      umbilical vein endothelial cells in culture exposed to squalamine. Squalamine
      treatment was found to retard two cellular events necessary for angiogenesis,
      inducing disorganization of F-actin stress fibers and causing a concomitant
      reduction of detectable cell the surface molecular endothelial cadherin (VE
      cadherin). We propose that the augmentation by squalamine of cytotoxicity from
      platinum-based therapies is attributable to interference by squalamine with the
      ability of stimuli to promote endothelial cell movement and cell-cell
      communication necessary for growth of new blood vessels in xenografts after
      chemotherapeutic injury to the tumor.

PMID- 11297270
TI  - Hepatocyte growth factor modulates vascular endothelial-cadherin expression in
      human endothelial cells.
AB  - Hepatocyte growth factor (HGF)/scatter factor (SF) is a cytokine exerting a wide
      range of biological functions on many cell types, including vascular endothelial
      cells. HGF/SF increases migration, motility, and dissociation of human umbilical
      vascular endothelial cells (HUVECs). This study demonstrated that such action of
      HGF/SF on HUVECs was achieved by regulation of the endothelial cell-specific
      cadherin, vascular endothelial (VE)-cadherin. HGF/SF induced a time-dependent
      reduction of VE-cadherin protein from HUVECs as shown by Western blotting and
      immunocytochemistry, accompanied by an increase in the migration of HUVECs. The
      change of VE-cadherin appeared at the mRNA level, as demonstrated by reverse
      transcription-PCR, with a decrease in the VE-cadherin signal. These results show,
      for the first time, that HGF/SF targets the endothelial cell-specific adhesion
      molecule VE-cadherin.

PMID- 11297271
TI  - Increased risk of incident pancreatic cancer among first-degree relatives of
      patients with familial pancreatic cancer.
AB  - It has been estimated that familial aggregation and genetic susceptibility play a
      role in as many as 10% of patients with pancreatic cancer (PC). The quantified
      prospective risk of PC among first-degree relatives of PC patients has not been
      investigated. Families enrolled in the National Familial Pancreas Tumor Registry
      (NFPTR) prior to September 1, 1998 were followed to estimate the risk and
      incidence of PC among first-degree relatives of patients with PC. Analyses were
      performed separately on kindreds with at least two first-degree relatives with PC
      (familial pancreatic carcinoma (PC); n = 150) at the time the kindred was
      enrolled in the NFPTR and on kindreds without a pair of affected first-degree
      relatives (sporadic PC; n = 191). A subanalysis was performed on familial PC
      kindreds containing three or more affected members at the time of enrollment in
      the NFPTR (n = 52). Risk was estimated by comparing observed new cases of PC
      during the observation period with expected numbers based on the United States
      population-based Surveillance, Epidemiology and End Results program data.
      Incidence was estimated using person-years risk analyses. During the
      observational period, six incident PCs developed in the first-degree relatives:
      two in the sporadic PC kindreds, and four in the familial PC kindreds. The PC
      risk in the sporadic PC kindreds was not significantly greater than expected
      [observed/expected = 6.5 (95% CI = 0.78-23.3)] with an incidence rate of
      24.5/10(5)/ year. There was a significantly increased 18-fold risk (95% CI = 4.74
      44.5) of PC among first-degree relatives in familial PC kindreds, with an
      incidence of 76.0/10(5)/year. In the subset of familial PC kindreds with three or
      more affected family members at the time of enrollment, there was a 57-fold (95%
      CI = 12.4-175) increased risk of PC and an incidence of 301.4/10(5)/year compared
      with the Surveillance, Epidemiology and End Result age-adjusted incidence of PC
      in the U.S. (8.8/10(5)/year). When stratified by age, the risk was largely
      confined to relatives over the age of 60. This study is the first analysis of
      incident PC occurring in familial PC kindreds. The risk and incidence of PC is
      exceptionally high among at-risk first-degree relatives in familial PC kindreds
      in which at least three first-degree relatives have already been diagnosed with
      PC. Familial PC kindreds are a reasonable high-risk group for PC screening and
      chemoprevention research.

PMID- 11297272
TI  - NIH symposium summary: organ preservation therapies for squamous cancers of the
      head and neck.
AB  - This symposium, sponsored by the NIH Office of Rare Diseases, the National Cancer
      Institute, the National Institute of Deafness and Other Communication Disorders,
      and the National Institute of Dental and Craniofacial Diseases, reviewed the
      current status of organ preservation therapies for head and neck cancers, as well
      as promising newer approaches for therapy and for toxicity amelioration.

PMID- 11297273
TI  - Egg marketing in national supermarkets: egg quality--part 1.
AB  - Two surveys were conducted to determine the quality of eggs offered to consumers
      in large supermarkets in various regions of the US. The first survey was
      conducted in California (CA) in 1994 and included 38 samples of large (L) and
      extra large (XL) white eggs in 15 markets. Individual eggs were weighed, candled,
      and broken out for Haugh unit (HU) determination. Regional differences in age of
      eggs, the number of eggs below 55 HU, and the percentage of cracked eggs were
      observed. The second survey was conducted in California (CA), Illinois (IL),
      Pennsylvania (PA), Texas (TX), North Carolina (NC), and New England (NE). This
      study included brown and white eggs and samples from 115 stores in 38 cities.
      Significant age, egg weight, HU, and cracked egg differences were observed
      between states. Brown and white eggs were different relative to age and HU, but
      egg weights and cracked eggs were statistically the same. The two surveys, 1994
      and 1996, within CA demonstrated very similar measurements when L-white eggs were
      compared.

PMID- 11297274
TI  - Egg marketing in national supermarkets: specialty eggs--part 2.
AB  - Large eggs promoted as having one or more features beyond conventional white or
      brown shell eggs (specialty eggs) were evaluated for quality and price in a
      national retail study. Subtypes of specialty eggs included: nutritionally altered
      eggs, organic eggs, fertile eggs, eggs from welfare-managed hens, or hens fed all
      vegetable diets. Extension Poultry Specialists in California (CA), Connecticut,
      Illinois, North Carolina, Pennsylvania and Texas conducted a survey of egg
      quality and price and compared 246 dozen specialty eggs with 390 dozen
      conventional white shell eggs during the summer of 1996. Age of the eggs based on
      carton dating indicated specialty eggs were older (16.5 d) than white eggs (11.7
      d). Average egg weights for specialty compared to white were 60.2 and 59.6 g,
      respectively. Interior egg quality evaluations including albumen height, Haugh
      units (HU), and percentage HU <55, indicated white eggs were superior (5.0 mm,
      67.5, and 10.6%, respectively) compared to specialty eggs (4.7 mm, 63.8, and
      16.3%). Although the percentage of cracked eggs was similar between specialty and
      white eggs (5.4 and 5.7%), the percentage of leakers was threefold higher for the
      specialty eggs (1.0 vs. 0.3%). Egg price was substantially higher for the
      specialty eggs, averaging $2.18/dozen with a range from 0.88 to $4.38, compared
      to white eggs, averaging $1.23/dozen and ranging from 0.39 to $2.35.

PMID- 11297275
TI  - Egg marketing in national supermarkets: products, packaging, and prices--part 3.
AB  - As part of a national retail egg quality study, the variety of shell eggs and egg
      products offered for sale, type of packaging, and price relationships were
      compared in five major metropolitan regions. A total of 81 stores in 28 cities
      were sampled in California (CA), Illinois (IL), North Carolina (NC), Texas (TX),
      and New England (NE). Data were recorded for the variety of brands, sizes, white
      or brown shell eggs, specialty eggs, liquid or frozen eggs, carton sizes, package
      labeling and coding, and price relationships of shell eggs, liquid, and frozen
      egg products displayed for sale. The total variety of shell eggs displayed per
      store was the greatest for CA and NE stores. Stores in CA and TX offered more (P
      < 0.05) variety of white shell eggs than did stores in the other states, whereas
      stores in NE displayed the greatest variety (P < 0.05) of brown shell eggs. The
      average number of liquid and frozen egg products was highest (P < 0.05) for NC
      stores. Packaging type, USDA labeling, and carton coding differed somewhat among
      states. The price per one dozen cartons of all white shell egg sizes was highest
      (P < 0.05) in CA stores, and the average liquid plus frozen egg product prices
      were higher in CA and NE stores compared to the other states. However, the ratio
      of liquid and frozen product prices to all large shell egg prices was among the
      lowest for CA and NC stores. These data indicate that product selection,
      packaging, and consumer prices for shell eggs and egg products varied
      considerably across five separate regions of the country.

PMID- 11297276
TI  - The toxicity of fumonisin B1, B2, and B3, individually and in combination, in
      chicken embryos.
AB  - Three recently described and toxicologically important mycotoxins, fumonisin B1
      (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), produced by Fusarium
      moniliforme in various grains, have been associated with a number of diseases in
      both humans and animals. The toxicity of purified FB1, FB2, and FB3, individually
      and in combination (3:1:1 ratio), were evaluated with regard to their embryo
      toxicity by injection of the toxins into the air cell of chicken eggs at 72 h of
      incubation. Under these conditions, FB1 at doses of 0, 2, 4, 8, 16, 32, and 64
      microg per egg resulted in embryonic mortality of 5, 12.5, 17.5, 20.0, 52.5,
      77.5, and 100%, respectively. The 50% lethal dose for FB1, when injected into the
      air cell of embryonating chicken eggs, was determined to be 18.73 microg per egg.
      A comparison of the toxicity of FB1, FB2, and FB3, individually and in
      combination (3:1:1 ratio), at doses of 16 microg of total fumonisin per egg,
      indicated that the toxicity of the fumonisins differed, FB1 being the most toxic.
      Microscopic examination of chicken embryos exposed to fumonisin did not reveal
      any gross developmental abnormalities; however, severe hemorrhages of the head,
      neck, and thoracic area of the dead embryos were evident.

PMID- 11297277
TI  - The effect of nipple height on broiler performance.
AB  - Two trials, using a total of 3,200 male broilers, were conducted to compare the
      effects of a trough drinker versus three different heights on a nipple drinker
      system on body weight gain and feed:gain. The broilers were housed in temperature
      controlled litter pens at 25 or 30 C. An 8-ft open trough was used. The nipple
      drinker heights were adjusted as 1) low (no neck stretch and drink from the side
      of the beak), 2) medium (stretch neck and drink from the end of the beak), and 3)
      high (first elevate breast, then stretch neck and drink from the end of the beak)
      positions. The nipple heights were adjusted twice weekly by visual inspection.
      The open drinker produced the heaviest birds. No significant treatment
      differences were observed for feed:gain at 25 C but increased numerically with
      increasing nipple height. This same pattern was evident at 30 C, but
      statistically significant differences did occur. Drinking from a nipple drinker
      is an unnatural drinking act for birds, and the greater the neck extension,
      especially during a panting situation, the more detrimental the effect on both
      body weight and feed:gain.

PMID- 11297278
TI  - Cecal volatile fatty acids and broiler chick susceptibility to Salmonella
      typhimurium colonization as affected by aflatoxins and T-2 toxin.
AB  - Four experiments were conducted using day-of-hatch, mixed-sex broiler chicks to
      evaluate the effects of aflatoxins and T-2 toxin on cecal volatile fatty acids
      (VFA) and the susceptibility to Salmonella colonization. All chicks in these
      experiments were challenged orally with 10(4) cfu of Salmonella typhimurium (ST)
      on Day 3. In Experiments 1 and 2, chicks were fed diets containing 0, 2.5, or 7.5
      mg aflatoxins/kg of diet and were allowed to develop their microflora naturally.
      In Experiment 3, all chicks were orally gavaged on the day of hatch with a
      competitive exclusion (CE) culture (PREEMPT) and were fed diets containing 0,
      2.5, or 7.5 mg T-2 toxin/kg. In Experiment 4, the chicks were fed diets
      containing 0, 7.5, or 15.0 mg T-2 toxin/kg and one-half of the chicks were orally
      gavaged on the day of hatch with the CE culture. In Experiments 1 and 2, with the
      exception of increased total VFA at 5 d in chicks fed the 7.5 mg T-2
      aflatoxins/kg diet, there were no treatment effects on cecal propionic acid,
      total VFA, or incidence or severity of ST colonization. In Experiment 3, the only
      alteration in concentration of cecal propionic acid or total VFA was a
      significant reduction in total VFA at 5 d in chicks fed the 2.5 mg T-2 toxin/kg
      diet. No significant treatment differences were observed for numbers of
      Salmonella cecal culture-positive chicks or for numbers of ST in the cecal
      contents. In Experiment 4, with minor exceptions, the chicks treated with the CE
      culture had higher cecal concentrations of propionic acid and were less
      susceptible to Salmonella colonization than the non-CE-treated chicks. In the non
      CE-treated chicks, T-2 toxin had no effect on any of the parameters, and 85 to
      90% of the chicks were Salmonella cecal culture-positive. In the CE-treated
      chicks, there was a decrease in propionic acid concentration at 3 and 11 d and an
      increase in susceptibility to Salmonella colonization of the chicks fed the 15.0
      mg T-2 toxin/kg diet. These results indicate that cecal concentrations of VFA can
      be affected by toxins, such as high concentrations of T-2 toxin, and that
      resistance to Salmonella colonization may be reduced. Further research is
      necessary to determine the biological significance of these changes.

PMID- 11297279
TI  - Acute heat stress-induced alterations in blood acid-base status and skeletal
      muscle membrane integrity in broiler chickens at two ages: implications for meat
      quality.
AB  - The effects of acute heat stress (AHS) on indices of respiratory thermoregulation
      and skeletal muscle damage (myopathy) were examined in broiler chickens at two
      ages (35 and 63 d of age); the relationships of these responses with changes in
      meat quality were assessed. Exposure to AHS significantly increased deep-body
      temperatures, panting-induced acid/base disturbances, and plasma creatine kinase
      (CK) activities, reflecting heat stress-induced myopathy (HSIM). The extent of
      the hyperthermia and disturbances in acid/base status and myopathy was
      significantly (P < 0.05) higher in the older birds. Consistent with AHS-induced
      alterations in thermoregulatory indices and muscle membrane integrity were
      changes in breast muscle glycolytic metabolism as indicated by lower muscle pH
      immediately postslaughter (pHi), increased water loss, and increased incidence of
      breast muscle hemorrhages. Values of pHi were lower and hemorrhage scores greater
      in the AHS birds at 63 d; drip losses were significantly higher in the 35-d-old
      birds. Exposure to AHS did not affect breast meat eating quality, although
      overall reductions in flavor attributes were observed in the older birds. We
      concluded that exposure to AHS induced disturbances in blood acid/base status and
      had a detrimental effect upon skeletal muscle membrane integrity. Muscle from
      broilers exhibited an increased sensitivity to AHS exposure with age. Alterations
      in antemortem blood acid/base status and muscle membrane integrity induced by AHS
      were associated (though not necessarily causally) with adverse effects upon
      breast meat quality. It is recommended that preslaughter exposure of broiler
      chickens to AHS should be avoided in order to reduce alterations in muscle
      metabolism and membrane integrity and undesirable meat characteristics.

PMID- 11297281
TI  - Nutritional evaluation of sunflower products for poultry as affected by the oil
      extraction process.
AB  - The nutritional value of sunflower seed (SFS) products was determined in two
      experiments using 180 adult Leghorn-type roosters (Hy-Line). In Experiment 1,
      press and solvent SFS oils were included in a basal diet at four graded levels
      (from 1.3 to 20%). Each diet was force-fed (30 g) to 10 roosters to determine
      their TMEn and true fat digestibility. Dietary TMEn and true digestible fat
      increased linearly (P < 0.0001) with oil inclusion. There were no differences in
      nutritional value between oils; their digestibility was 90%, which led to 8,385
      +/- 39 kcal TME/kg DM. In Experiment 2, the effect of oil extraction on TMEn,
      true fat, and amino acid digestibility (TAAD) of SFS products was studied.
      Several products were derived from the oil extraction process: SFS, press
      extracted SFS (PESFS), and SFS meal (SFSM), as well as recombined products (mix
      of meal and oil) of SFS and PESFS, and were force-fed directly to 10 roosters
      each. Oil extraction produced a decrease (P < 0.0001) in true fat digestibility,
      TAAD, and TMEn (4,555, 2,591, and 1,754 +/- 59 kcal/kg DM for SFS, PESFS, and
      SFSM, respectively). Digestible fat content explained the difference between TME,
      of SFS and PESFS, whereas the difference between the TMEn of PESFS and SFSM was
      lower than expected. Recombined and original products had similar (P > 0.05)
      TMEn, despite solvent oil showing higher digestibility when released. Recombined
      SFS showed lower (P < 0.005) TAAD than original SFS (84.2 and 90.4%,
      respectively), indicating protein damage caused by heat and mechanical pressure.
      However, there were no differences, except for lysine, in TAAD between original
      and recombined PESFS (86.3 and 86.6%, respectively); both feeds showed higher (P
      < 0.05) TAAD than SFSM (83.9%), which indicates a positive effect of fat addition
      at this step.

PMID- 11297280
TI  - Efficacy of diclazuril in comparison with chemical and ionophorous anticoccidials
      against Eimeria spp. in broiler chickens in floor pens.
AB  - Two 42-d floor pen studies were conducted with commercial broiler chickens to
      measure the efficacy of 1 ppm diclazuril in the starter or grower diet in shuttle
      programs with 66 ppm salinomycin. Study 1 compared a salinomycin to diclazuril
      (starter to grower diet) shuttle treatment with salinomycin to salinomycin,
      salinomycin to 100 ppm monensin, salinomycin to 99.8 ppm lasalocid, and
      unmedicated treatments. Study 2 compared a diclazuril to salinomycin (starter to
      grower) shuttle treatment with 125 ppm nicarbazin to salinomycin, 79.2 ppm
      narasin + nicarbazin to salinomycin, 125 ppm zoalene to salinomycin, and
      unmedicated treatments. Fifty 1-d-old chicks were randomly allotted to each of 10
      pens per treatment in each study using a randomized complete block design.
      Starter (Days 0 to 21) and grower (Days 22 to 37) diets in each study contained
      55 ppm bacitracin methylene disalicylate. The finisher diet (Days 38 to 42) in
      each study was unmedicated. Birds were inoculated via their feed on Day 22 (Study
      1) or Day 15 (Study 2) with a mixed inoculum of Eimeria acervulina, Eimeria
      maxima, and Eimeria tenella. Four birds per pen (two male and two female) were
      randomly selected in each study for coccidial lesion scores on Day 6
      postinoculation. These studies demonstrated that the use of 1 ppm diclazuril in
      shuttle programs was highly efficacious against a mixed inoculum of Eimeria spp.
      in comparison with nicarbazin, narasin + nicarbazin, and zoalene in starter diets
      and salinomycin, monensin, and lasalocid in grower diets.

PMID- 11297282
TI  - Changes in growth and function of chick small intestine epithelium due to early
      thermal conditioning.
AB  - The effect of exposure to heat at 3 d of age on small intestine functionality and
      development was assayed by measuring villus size, proliferating enterocytes, and
      brush-border membrane (BBM) enzyme expression and activity. Results showed that
      thermal conditioning caused an immediate effect characterized by lowered
      triiodothyronine (T3) level, reduced feed intake, and depressed enterocyte
      proliferation and BBM enzyme activity. A second series of effects, observed 48 h
      posttreatment, was characterized by elevated T3, increased feed intake, increased
      enterocyte proliferation, and higher expression and activity of BBM enzymes. The
      association between ambient temperature, feed intake, growth rate, and plasma T3
      levels was reflected in the structure and function of the intestinal tract. The
      results suggest that thermal conditioning at an early age influences T3
      concentrations, which in turn alter the intestinal capacity to proliferate, grow,
      and digest nutrients. However, these experiments were not able to discriminate
      between effects due to feed intake and those due to thermal conditioning. The
      treatments modulated changes in the intestinal tract following thermal treatment.

PMID- 11297283
TI  - Performance of broilers fed limited quantities of feed or nutrients during seven
      to fourteen days of age.
AB  - Three experiments were conducted with male broilers to study the effects of early
      life undernutrition. In all studies, treatments were represented by three or four
      replicate floor pens, each containing 30 to 40 birds. In Experiment 1, broilers
      were fed at 0.75 kcal ME/gBW0.67 for 4 d, 1.5 kcal ME/gBW0.67 for 5 d or 2.25
      kcal ME/gBW0.67 for 6 d, all imposed beginning at 6 d of age. Birds were smaller
      following feed restriction (P < 0.01) although growth compensation occurred, and
      at 49 d all restricted birds were heavier (P < 0.01) than full-fed control birds.
      Improved growth was associated with improved feed conversion (P < 0.01), although
      carcass composition was unchanged. In a second study, birds were fed at 0.75 kcal
      ME/gBW0.67 for 3, 4, or 5 d, starting at either 4, 7, or 10 d of age. When feed
      restriction was applied early, or for shorter periods of time, growth
      compensation occurred (P > 0.05). With other more severe feed restriction, birds
      were smaller (P < 0.05) at 49 d compared to controls. Feed conversion was
      improved following prior feed restriction (P < 0.01, 0 to 49 d). In a third
      trial, broilers were fed a starter diet diluted with 50% oat hulls. Birds failed
      to consume enough of this diluted feed, and so were initially smaller. However 49
      d weight was not affected (P > 0.05). When periods of 24-h feed withdrawal were
      imposed in conjunction with the diluted diets, birds were underweight at 49 d. It
      is concluded that physical feed restriction at 0.75 to 1.5 kcal ME/gBW0.67
      imposed for 3 to 4 d in the second week of life currently presents the best
      option as a means of controlling broiler growth so as to improve feed efficiency.

PMID- 11297284
TI  - Phosphorus requirements of broiler chicks three to six weeks of age as influenced
      by phytase supplementation.
AB  - Two studies of identical design were conducted in battery brooders utilizing male
      chicks of a commercial strain. The birds were grown to 3 wk on diets with
      adequate P and from 3 to 6 wk were fed diets ranging from 0.10 to 0.45%
      nonphytate P (nPP) in increments of 0.05%, with or without supplementation with
      800 units of phytase per kilogram of diet. Measurements included BW gain, feed
      conversion ratio (FCR), mortality, tibia ash, and fecal P content. Nonlinear
      regression was used to estimate nPP needs for optimizing BW gain, feed
      conversion, and tibia ash. In the absence of phytase, nPP levels of 0.33, 0.186,
      and 0.163% were required to optimize tibia ash, BW gain, and FCR, respectively.
      The estimated level for optimum tibia ash is in close agreement with current NRC
      (1994) recommendations. In the presence of 800 units of phytase per kilogram, nPP
      levels of 0.24, 0.151, and 0.109% were needed to optimize tibia ash, BW gain, and
      FCR, respectively. Fecal phosphorus levels were markedly reduced at the lower P
      levels. Further studies are needed to determine whether maximum tibia ash values
      are needed to sustain optimum production of market broilers.

PMID- 11297285
TI  - Effect of dietary supplementation with rosemary extract and alpha-tocopheryl
      acetate on lipid oxidation in eggs enriched with omega3-fatty acids.
AB  - The antioxidant effect of dietary supplementation with 500 or 1,000 mg/kg of a
      commercial rosemary extract vs. 200 mg/kg of alpha-tocopheryl acetate (alpha-TA)
      on the lipid oxidative stability of omega3-fatty acid (FA)-enriched eggs was
      compared. Lipid oxidation was measured in fresh eggs by the lipid hydroperoxide
      level and malonaldehyde content. Stability to iron-induced lipid oxidation was
      also measured. Results showed the clear antioxidant effect of dietary alpha-TA
      supplementation on omega3-FA enriched eggs. In contrast, dietary supplementation
      with rosemary extract showed no effect on any of the lipid oxidation parameters
      evaluated.

PMID- 11297286
TI  - Pulmonary wedge pressures confirm pulmonary hypertension in broilers is initiated
      by an excessive pulmonary arterial (precapillary) resistance.
AB  - High retrograde pressure through the pulmonary venous system caused by failure of
      the left ventricle or left atrio-ventricular valve may result in the elevated
      pulmonary arterial pressure and right ventricular hypertrophy associated with
      pulmonary hypertension syndrome (PHS; ascites) in broiler chickens. In the
      present study, unanaesthetized male broilers from an ascites-resistant line, the
      base population from which the resistant line was derived, and a separate
      unselected line were used to determine whether changes in wedge pressure (thought
      to be similar to left atrial pressure) are predictive of differences in the
      pulmonary arterial pressure of clinically healthy and pre-ascitic broilers.
      Venous, right atrial, right ventricular, pulmonary arterial, and wedge pressures
      were obtained by inserting a catheter into a wing vein and progressively
      advancing the catheter into a pulmonary branch artery until the catheter tip
      became wedged in and occluded the flow through a terminal artery. Mean right
      ventricular and pulmonary arterial pressures were lower in the resistant line
      than in the base population, but wedge pressures did not differ between the
      resistant, base, and unselected lines. Right:total ventricular weight ratios
      (RV:TV) and the percentage saturation of hemoglobin with oxygen in arterial blood
      ranged in value from 0.18 to 0.44 and 65 to 96%, respectively. Wedge pressure,
      however, remained similar when pre-ascitic broilers with high RV:TV values and
      low oximetry values were compared with clinically healthy broilers. In all birds,
      whether healthy or showing pre-ascitic characteristics, the wedge pressure was
      slightly higher than the right atrial pressure but substantially lower than
      pulmonary arterial pressure. These observations provide definitive proof that
      pulmonary hypertension is initiated as a consequence of excessive pulmonary
      arterial or arteriole resistance. Pulmonary venous pressure is estimated by
      measuring the pulmonary arterial wedge pressure, and high wedge pressures would
      be evident if pulmonary hypertension was caused by the elevated downstream
      resistances associated with left-sided heart failure.

PMID- 11297287
TI  - Electron transport chain defect and inefficient respiration may underlie
      pulmonary hypertension syndrome (ascites)-associated mitochondrial dysfunction in
      broilers.
AB  - By using a series of chemical inhibitors of mitochondrial respiration, a site
      specific defect in the electron transport chain was identified in mitochondria
      obtained from broilers with pulmonary hypertension syndrome (PHS; ascites).
      Located at the succinate:ubiquinone oxido-reductase (Complex II:CoQ) interface,
      this defect would allow electrons to leak from the respiratory chain and consume
      oxygen by forming reactive oxygen species at a greater rate than in control
      mitochondria. Lower levels of the primary antioxidants, alpha- and beta
      tocopherol, and glutathione (GSH) in PHS mitochondria confirmed the presence of
      oxidative stress. Respiration studies of PHS liver mitochondria also revealed
      disease-associated decreases in the respiratory control ratio (RCR, an index of
      electron transport chain coupling). Differences in the RCR as well as the
      adenosine diphosphate (ADP) to O ratio (an index of oxidative phosphorylation)
      between control and PHS mitochondria were accentuated by sequential additions of
      ADP to isolated mitochondria. In a second experiment, similar improvements in
      functional indices following sequential additions of ADP and responses to
      respiratory chain inhibitors were observed in liver mitochondria isolated from
      Single Comb White Leghorn (SCWL) males (resistant to PHS) similar to that
      observed in control broiler mitochondria in Experiment 1. The combined results
      indicate the presence of a site-specific defect at either Complex II, ubiquinone,
      or both in liver mitochondria obtained from broilers with PHS that may be
      responsible for the oxidative stress and mitochondrial dysfunction observed in
      this costly metabolic disease.

PMID- 11297288
TI  - Lung mitochondrial dysfunction in pulmonary hypertension syndrome. I. Site
      specific defects in the electron transport chain.
AB  - The main objectives of this study were to determine a) site-specific defects in
      the electron transport chain of lung mitochondria of broilers with pulmonary
      hypertension syndrome (PHS), b) if these defects are attenuated by high dietary
      vitamin E, and c) if these defects have a genetic basis. In Experiment 1, lung
      mitochondria were isolated from broilers with and without PHS fed diets
      containing 15 IU and 100 IU dl-alpha-tocopherol acetate/kg (VE); the four
      treatments were control, VE, PHS, and VE-PHS, respectively. Hydrogen peroxide
      (H2O2) generation in isolated lung mitochondria was monitored by
      dichlorofluorosein (DCF) fluorescence in response to chemicals that inhibit
      electron flow at specific sites on the electron transport chain using a 96-well
      microplate with Cytoflour (excitation/emission 480/530 nm). Basal H2O2 production
      was higher in PHS than in control mitochondria. Differences in H2O2 production
      between control and PHS were magnified by inhibition of Complexes I and III
      (Coenzyme Q) of the respiratory chain in mitochondria. Functional defects in PHS
      mitochondria were attenuated by high dietary VE. In Experiment 2, basal H2O2
      production and that following inhibition of Complexes I and III were lower in
      lung mitochondria isolated from broilers selected for genetic resistance to PHS
      than in nonselected birds in the base population. The results of this study
      indicate that site-specific defects in Complexes I and III may underlie lung
      mitochondrial dysfunction in broilers with PHS, that these defects are attenuated
      by high dietary vitamin E, and that these defects may be related to genetic
      predisposition to PHS.

PMID- 11297289
TI  - Influence of extraction temperature on amounts and quality of rendered chicken
      fat recovered from ground or homogenized skin.
AB  - A study was undertaken to determine the influence of extraction process on
      recovery and quality of fat from chicken skin. In order to do so, 20-kg batches
      of skin were ground (9.5 mm plate) or homogenized in a colloidal mill (0.2-mm
      knife set), then heated to 50 or 80 C to rupture fat cells. The fat was recovered
      by centrifugation and was evaluated for composition, appearance, and stability. A
      maximum amount of fat (89.6% of the fat initially contained in skin) was
      recovered from homogenized skin heated to 80 C, whereas heating ground skin to 50
      C yielded the lowest fat recovery (51.5% of skin fat content). In general, fat
      composition and appearance were little affected by extraction conditions, with
      the exception that the fat extracted from homogenized skin contained more (P < or
      = 0.001) unsaponifiable cell membrane constituents (0.17 to 0.20%), including
      antioxidant tocopherol fractions (10.3 microg/ml), than the fat extracted from
      ground skin (0.08% and 7.5 to 8.3 microg/ml, respectively). This difference
      likely contributed to the greater oxidative stability of the fat extracted from
      homogenized skin, which was observed in Schaal oven tests.

PMID- 11297290
TI  - Electrical stunning, hot boning, and quality of chicken breast meat.
AB  - The first experiment was conducted to determine the effects of varying voltage,
      20, 40, 80, and 100 V at 60 Hz, on stunning efficiency, blood loss, and carcass
      defects. In the second experiment, the same parameters were evaluated to
      determine the effects of varying frequency, 60, 200, 350, 500, and 1,000 Hz at 40
      V. A control group for both experiments was not stunned. At 40V, 30 to 50 mA, 90%
      of the birds were unconscious, as shown by no response to comb piercing, and
      blood loss was maximized (55.3%). When varying the stunning frequency, maximum
      blood loss (73.1%), 90% of the birds were unconscious, and minimum carcass
      defects were observed at 1,000 Hz, 40 V. In the third experiment, birds were
      stunned at 40 V, 1,000 Hz and deboned immediately after defeathering (hot boning)
      and chilled or deboned after passing through all stages of a commercial abattoir
      operation (conventional boning). Control lots were unstunned and followed normal
      abattoir stages. Average shear value was significantly lower for stunned compared
      to unstunned birds (6.0 vs. 7.1 kg/g), although tenderness scores, as measured by
      a trained panel, were not significantly different (6.6 for stunned birds vs. 6.1
      for unstunned). Scores for juiciness were also not significantly different (5.5
      for stunned vs. 5.8 for unstunned). Average shear value was also significantly
      lower for conventionally boned birds (5.2 kg/g) than for hot boned birds (7.9
      kg/g). Sensory analysis confirmed the shear value results. Conventionally boned
      breasts had an average tenderness score of 7.4 vs. an average of 5.3 for hot
      boned breast. No statistical differences were observed with respect to juiciness,
      although a score of 6.2 was observed for conventionally boned breast meat vs. a
      score of 5.1 for hot boned breast meat.

PMID- 11297291
TI  - Heat transfer properties, moisture loss, product yield, and soluble proteins in
      chicken breast patties during air convection cooking.
AB  - Chicken breast patties were processed in an air convection oven at air
      temperatures of 149 to 218 C, air velocities of 7.1 to 12.7 m3/min, and air
      relative humidities of 40 to 95%. The air humidity was controlled via introducing
      steam into the oven. The patties were processed to a final center temperature of
      50 to 80 C. Heat flux, heat transfer coefficient, moisture loss in the cooked
      chicken patties, the product yield, and the changes of soluble proteins in the
      product were evaluated for the cooking system. During cooking, heat flux varied
      with the processing time. Heat flux increased with increasing air humidity. The
      effective heat transfer coefficient was obtained for different cooking
      conditions. Air humidity in the oven affected the heat transfer coefficient. The
      moisture loss in the cooked products increased with increasing the final product
      temperature and the oven air temperature. The soluble proteins in the cooked
      patties decreased with increasing the final product temperature. Increasing
      humidity increased heat transfer coefficient and therefore reduced cooking time.
      Reducing oven temperature, reducing internal temperature, and increasing air
      humidity increased the product yield. Soluble proteins might be used as an
      indicator for the degree of cooking. The results from this study are important
      for evaluating commercial thermal processes and improving product yields.

PMID- 11297292
TI  - Thermal inactivation of Salmonella senftenberg and Listeria innocua in ground
      chicken breast patties processed in an air convection oven.
AB  - Ground chicken breast patties were thermally processed in a lab-scale air
      convection oven at air temperatures of 163, 177, 190, 204, or 218 C to final
      patty center temperatures of 50, 55, 60, 65, 70, 75, or 80 C. The cooking time
      increased with increasing product temperature and decreased with increasing oven
      air temperature. Prior to thermal processing, approximately 7 log10(cfu/g) of
      Salmonella senftenberg and Listeria innocua were inoculated into the chicken
      patties. Survival of S. senftenberg and L. innocua decreased with increasing
      patty temperature. After the patties were processed to a final center temperature
      of 70 to 80 C, 1 to 4 log10 (cfu/g) of S. senftenberg and 3 to 5 log10(cfu/g) of
      L. innocua were detected in the cooked patties. A significant difference in the
      thermal inactivation of S. senftenberg and L. innocua was obtained between the
      chicken patties cooked in an air convection oven and the patties cooked in a
      water bath. More surviving S. senftenberg and L. innocua were found in the
      patties cooked in an air convection oven than in the patties cooked in a water
      bath.

PMID- 11297293
TI  - Random amplified polymorphic DNA fingerprints for identification of species in
      poultry pate.
AB  - Because some fraudulent or unintentional mislabeling occurs that can be
      undetected, resulting in lower quality pate, and because some population groups,
      for philosophical or religious reasons, do not wish to eat meat from certain
      species, a new procedure was developed and evaluated to detect pate species
      composition by randomly amplified polymorphic DNA (RAPD). The RAPD method was
      used to generate fingerprint patterns for pork, chicken, duck, turkey, and goose
      meats. Ten DNA samples from pork, chicken, turkey, and duck meats were tested to
      confirm the effectiveness and specificity. Specific results for each species were
      obtained by the RAPD method. Sensitivity of the method was studied by DNA
      dilution in each species, detecting as little as 250 pg of DNA. Isolations of DNA
      from 30 pates (tinned and untinned) were carried out, and an optimal DNA was
      obtained for using as template DNA in polymerase chain reaction (PCR). The RAPD
      PCR pattern was useful to identify species composition of pork, duck, duck-pork,
      goose, and poultry pates. This study demonstrates the usefulness of RAPD
      fingerprinting to distinguish between species in pates.

PMID- 11297294
TI  - Avoidable mortality in New Zealand, 1981-97.
AB  - OBJECTIVE: To describe avoidable mortality in New Zealand, including trends and
      variations between groups by age, gender, ethnicity and degree of deprivation.
      METHOD: New Zealand Health Information Service mortality unit records, 1981 to
      1997, were classified as 'avoidable' or 'unavoidable' based on a reassessment of
      ICD9 codes and an upper age limit of 75 years. 'Avoidable' causes of death were
      further subcategorised according to the level of intervention involved (primary,
      secondary or tertiary). Deaths were assigned a deprivation score using a Census
      based small area deprivation index, the NZDep96. Mortality rates were age
      standardised by the direct method, with Segi's world population as the reference.
      RESULTS: Avoidable mortality declined 38% from 1981 to 1997; unavoidable
      mortality declined only 9%. In 1996-97 almost 70% of deaths in the 0-74 age range
      were still considered to be potentially avoidable. Almost 80% of avoidable deaths
      occur in the 45-74 age group. These deaths are dominated by the emergence of
      chronic diseases such as ischaemic heart disease, diabetes and smoking-related
      cancers. In younger age groups, injury (including suicide) dominates avoidable
      mortality. Males experience a greater burden of avoidable mortality than females-
      a relative excess of 54% (approximately 2,000) in 1996-97. The gender difference
      is largely attributable to diseases and injuries amenable to primary prevention,
      with the largest single contribution coming from ischaemic heart disease. The
      ethnic gap in avoidable mortality remains wide: rates for Maori and Pacific
      people were 2-2 1/2 times higher than European rates in 1996-97. Similar
      gradients are seen with deprivation. CONCLUSION AND IMPLICATIONS: Avoidable
      mortality analysis provides a useful tool for evidence-based health needs
      assessment and health policy development.

PMID- 11297295
TI  - Fatal crashes involving young male drivers: a continuous time Poisson change
      point analysis.
AB  - BACKGROUND: In an effort to reduce road trauma, the New Zealand government
      implemented a series of intervention programs over the last decade, with young
      male drivers as the main target audience. Previous research, however, found
      little or no evidence that these programs had any impact on this group of drivers
      despite an apparent decrease in their crash involvement. OBJECTIVE: To determine
      the approximate time when the decrease in the number of fatal crashes involving
      young male drivers occurred. METHOD: A Poisson change-point estimator was used to
      locate the most likely point where a decrease in the average number of monthly
      crashes had occurred. RESULTS: The most likely time of change was found to
      coincide with the time when the Transport Act 1992 was debated and passed in
      Parliament. The publicity given to the issue and the Government's signal of
      impending actions were sufficient to induce a significant change in the
      behaviours of young male drivers. IMPLICATIONS: This result can partially
      reconcile the difference between the apparent reduction in the number of fatal
      crashes involving young male drivers and the inability of previous studies to
      find a significant impact of the various intervention programs since the change
      occurred prior to the actual implementation of the programs. Nevertheless, it was
      argued that the implementation of the programs subsequently was necessary in
      sustaining the reduction.

PMID- 11297296
TI  - Opportunities for control of coronary heart disease in Australia.
AB  - OBJECTIVE: To estimate the number of coronary events that could be prevented in
      Australia each year by the use of preventive and therapeutic strategies targeted
      to subgroups of the population based on their levels of risk and need. METHODS:
      Estimates of risk reduction from the published literature, prevalence estimates
      of elevated risk factor levels from the 1995 National Health Survey and treatment
      levels from the Australian collaborating centres in the World Health
      Organization's MONICA Project were used to calculate numbers of coronary events
      preventable among men and women aged 35-79 years in Australia. RESULTS:
      Approximately 14,000 coronary events could be avoided each year if the mean level
      of cholesterol in the population was reduced by 0.5 mmol/L, smoking prevalence
      was halved and prevalence of physical inactivity was reduced to 25%. This
      represents a reduction in coronary events of about 40%. Even with less optimistic
      targets, a reduction of 20% could be attained, while the achievement of some
      internationally recommended targets could lead to almost 50% reduction. In the
      short term, aggressive medical treatment of people with elevated levels of risk
      factors and established coronary disease offers the greatest opportunity for
      reducing coronary events. CONCLUSION: A comprehensive approach to reduce levels
      of behavioural and biological risk factors and improve the use of effective
      treatment could lead to a large reduction in coronary event rates. In the long
      term, primary prevention--especially to reduce smoking, lower cholesterol levels
      and increase exercise--has the potential to reduce the population levels of risk
      and hence contain the national cost of coronary disease.

PMID- 11297298
TI  - Mortality from aortic aneurysms in Australia, 1968 to 1997.
AB  - OBJECTIVES: Describe trends in mortality for aortic aneurysms in Australia for
      the period 1968 to 1997. DESIGN: Descriptive study of time trends in mortality.
      MAIN OUTCOME MEASURE: Age-sex-standardised mortality rates with statistical
      analysis of trends using negative-binomial regression. RESULTS: While overall
      mortality rates for aortic aneurysms remained relatively constant for the period
      1968 to 1992 in Australia, there has been a small but significant reduction in
      the rate from then until the end of the series in 1997. When different types of
      aneurysms are considered, there have been increases in the rates associated with
      abdominal aortic aneurysms and thoracic aortic aneurysms, while those for
      dissecting aortic aneurysms have declined. Most significantly, mortality rates
      for unspecified aortic aneurysms have declined. CONCLUSION: Aortic aneurysm
      mortality has declined in Australia in recent years. The reasons for this are
      unclear. While there have been increases associated with abdominal aortic
      aneurysm mortality, this is likely to be a result of more precise coding of death
      rather than any real increase in mortality.

PMID- 11297299
TI  - Birthweight changes in the pilot phase of the Strong Women Strong Babies Strong
      Culture Program in the Northern Territory.
AB  - OBJECTIVE: The Strong Women Strong Babies Strong Culture Program had specific
      goals to increase infant birthweights by earlier attendance for antenatal care
      and improved maternal weight status. Starting in August 1993, Aboriginal women in
      three pilot communities worked with pregnant women in a program that emphasised
      both traditional practices and Western medicine. METHOD: Two sources of data were
      used to examine different aspects of program effects. RESULTS: Data from the NT
      Midwives Collection shows that the mean birthweight of infants of Aboriginal
      women increased by 171 g between 1990/91 and 1994/95 in the pilot communities and
      by 92 g in the surrounding three rural regions. Data extracted from clinic
      records in the pilot communities found that changes in maternal weight were
      associated with change in birthweight over time. CONCLUSION: Changes in
      birthweight coincide with the commencement of the program and are larger than the
      secular trend in surrounding communities. IMPLICATIONS: Ongoing evaluation of the
      expanded program will help to determine the extent to which the change in
      birthweight can be attributed to the program and whether the effects can be
      replicated.

PMID- 11297300
TI  - Economics, competition and the regulation of public health risks.
AB  - OBJECTIVE: The efficiency of regulation of public health risks has been
      questioned on the grounds that the costs of regulation may outweigh the benefits.
      There are strong arguments that risk management is best left to the market place,
      where individual consumers can make the trade-off between risk and the forgone
      benefits of reduced consumption of hazardous products. The paper reviews the
      economic arguments for the regulation of health risks and the use of safety
      standards. RESULTS: There are five key arguments for regulation of public health
      risks. Consumers misperceive the hazards of products and therefore take more
      risks than they would if fully informed. The provision of information has certain
      public goods characteristics (it is non-rival). There may be economies of scale
      in collecting, providing and disseminating information that is costly to acquire.
      The private decision maker may not be the person bearing the whole risk, exposing
      others to risk e.g. children. If public policy has chosen to provide public
      finance for health care it may be efficient to discourage risk taking by
      individuals even if that risk taking is optimal from the individual's
      perspective. CONCLUSION: There are arguments for public intervention to reduce
      private health risks and regulation of risk is a legitimate tool to achieve the
      socially optimal level of risk in certain circumstances. Private subjective
      assessment of risk may not capture the full social benefits of risk reduction.
      Regulation by safety standards however may fail to capture the full range of
      concerns about risk, including avoiding catastrophe, taking personal control of
      risk, and a distrust of expert opinion.

PMID- 11297302
TI  - Public health, private body.
AB  - A number of comparatively recent epistemological shifts draw attention to the
      body, among them developments in social (including feminist) theory and gender
      studies. In many social science and humanities disciplines, there is now
      considerable research and debate about notions of embodiment. Yet despite the
      fact that our subject matter is, ultimately, the life and death of human bodies,
      public health has remained largely silent on the question of what bodies are and
      how our public health work, whether academic or applied, is shaped by ideas about
      embodiment. Consequently, public health notions of the body remain implicit,
      ambiguous, often contradictory and incoherent. In this discussion, I strive to
      make explicit what some of our implicit ideas might be, to speculate on why
      bodies are excluded from most public health discourse, how that exclusion is
      achieved, and the consequences for public health research and practice. In an
      active consideration of the fundamental subject matter of public health, I invite
      attention to where and how greater self-consciousness about embodiment and its
      consequences might instigate shifts in public health thinking and action.

PMID- 11297301
TI  - A case-control study of risk factors for asthma in New Zealand children.
AB  - OBJECTIVE: As in other English-speaking countries, asthma is a major and
      increasing health problem in New Zealand. This study examined the risk factors
      for asthma in children aged 7-9. METHODS: Cases and controls were randomly
      selected from participants in the Wellington arm of the International Study of
      Asthma and Allergies in Childhood (ISAAC). Cases were children with a previous
      diagnosis of asthma and current medication use (n=233), and controls were
      children with no history of wheezing and no diagnosis of asthma (n=241). RESULTS:
      After controlling for confounders, factors significantly associated with asthma
      were maternal (OR=3.36, 95% CI 1.88-5.99) and paternal asthma (OR-2.67, 95% CI
      1.42-5.02), and male sex (OR=1.81, 95% CI 1.17-2.81). Children from social
      classes 5 and 6 or with unemployed parents (OR=2.32, 95% CI 1.22-4.44) were
      significantly more likely to have asthma than children in social classes 1 and 2.
      There was no significant association between having polio vaccination (OR=2.48,
      95% CI 0.83-7.41), hepatitis B vaccination (OR=0.66, 95% CI 0.42-1.04) or
      measles/mumps/rubella vaccination (OR=1.43, 95% CI 0.85-2.41) and asthma.
      CONCLUSIONS: This study has confirmed the associations of family history and
      lower socio-economic status with current asthma in 7-9 year old children. The
      role of vaccinations requires further research.

PMID- 11297303
TI  - Risk behaviours of young Indo-Chinese injecting drug users in Sydney and
      Melbourne.
AB  - OBJECTIVE: To investigate patterns of drug use and injection-related risk
      behaviours among young Indo-Chinese injecting drug users (IDUs). METHOD: Cross
      sectional survey. A structured questionnaire was administered to 184 Indo-Chinese
      IDUs aged 15 to 24 in Sydney and Melbourne. Participants were recruited using
      snowball sampling techniques; measures included patterns of heroin and other drug
      use, injection-related risk behaviours, perceived susceptibility to HIV and HCV
      infection and access to services. RESULTS: Despite perceived high availability of
      sterile injecting equipment, 36% had ever shared a needle and syringe and 22% had
      done so in the preceding month. Lifetime sharing was significantly associated
      with duration of injecting, history of incarceration and residence in Sydney.
      Sharing of injecting paraphernalia other than needles and syringes was also
      common, with young women and Sydney residents significantly more likely to report
      sharing equipment in the preceding month. CONCLUSIONS: Young Indo-Chinese IDUs
      are at high risk of infection with hepatitis C and other blood-borne viruses.
      Results indicate an urgent need for culturally appropriate and sustainable risk
      reduction programs which specifically target this population. IMPLICATIONS:
      Health services must respond swiftly to implement effective blood-borne virus
      prevention programs for young Indo-Chinese IDUs. Failure to do so may sustain the
      current epidemic of hepatitis C among IDUs.

PMID- 11297304
TI  - Cervical screening in migrants to Australia.
AB  - OBJECTIVE: To examine differentials and time trends in self-reported Pap test
      rates by migrant status from the 1989/90 and 1995 Australian National Health
      Surveys (NHS). METHOD: Unit record data for females with the variables of
      interest were extracted from the 1989/90 and 1995 NHS and combined. The
      dichotomous outcome variables were 'ever had a Pap test' and 'had a Pap test
      within three years'. The principal study factor was country-of-birth, but
      language spoken at home (English or not) was also examined. The indirect age
      standardised screening ratio was used to calculate proportions of 'ever had a Pap
      test' and 'had a Pap test within three years' and differences were tested
      statistically using logistic regression analysis for each year of survey by
      migrant status. RESULTS: Odds ratios for rates of reporting 'ever had a Pap test'
      were significantly lower in women born in southern Europe, Italy, other
      countries, southern Asia, Middle East, Greece and South-East Asia compared with
      Australian-born. Reported rates of 'ever had a Pap test' were significantly
      higher in the 1995 NHS (p<0.001). There were significant increases in screening
      for the Australian-born, New Zealand-born, and women born in southern Europe,
      South-East Asia, South Asia and Italy, and both English and non-English speakers
      over the 1989/90 and 1995 NHSs. Odds ratios for reporting 'had a Pap test within
      three years' showed significantly lower ORs for women born in the UK, Other
      countries, Middle East, Greece, and South-East Asia compared with the Australian
      born. CONCLUSIONS: This study reveals differentials in reported Pap test
      behaviour by country-of-birth in Australia and that reported screening rates have
      improved from the 1989/90 NHS to 1995 NHS in most country-of-birth groups.

PMID- 11297305
TI  - Trends in sun protection behaviour among Australian young adults.
AB  - OBJECTIVE: To study changes in sun protection behaviour, exposure and sunburn
      that occur from late adolescence to young adulthood. METHOD: A longitudinal
      design was used to survey a cohort on their sun-protection behaviour from the
      middle of their final year at school to more than three years after finishing
      school. RESULTS: Males reported higher exposure, less use of sunscreen and deeper
      tans than females. Yet males wore hats more frequently. People with skin that
      just burnt were more likely to protect themselves from the sun than people with
      skin that tanned. Longitudinally, the level of reported exposure and the depth of
      tan declined, frequency of covering up, hat wearing and sunscreen use remained
      unchanged, and a slight U-shaped trend was observed for sunburn. CONCLUSIONS:
      Young adulthood may be an important time where deteriorating trends for sun
      protection found in the teen years are averted. Males are at greater risk of sun
      exposure than females. IMPLICATIONS: It is recommended that health promotion
      programs capitalise on the trend of improved sun-protective behaviours during the
      transition from adolescence to young adulthood, with a particular focus on young
      men.

PMID- 11297306
TI  - Increasingly inequitable distribution of general practitioners in Australia, 1986
      96.
AB  - OBJECTIVE: To document trends in the distribution of general practitioners (GPs)
      in Australia between 1986 and 1996, adjusted for community need. METHODS: Data on
      the location of GPs, population size and crude mortality in statistical divisions
      (SD) were obtained from the Australian Bureau of Statistics Census of Population
      and Housing in 1986 and 1996. From these data, we calculated measures of
      distribution equality (number of people sharing each GP in each SD) and
      distribution equity (number of people sharing each GP divided by the crude
      mortality rate; the Robin Hood Index), and analysed temporal changes in the
      distribution of GPs. RESULTS: Nationally, the number of people sharing each GP
      fell 11% from 1,038 in 1986 to 921 in 1996. However, in 41 of 57 SDs (72%,
      p=0.01) the number of people sharing a GP actually increased over this time, and
      the average Robin Hood Index across SDs fell from 0.943 to 0.783 (p=0.004),
      indicating increasingly inequitable distribution. Comparing the Robin Hood Index
      values of all SDs ranked in pairs, the value fell in 53 of 57 (93%, p<0.001)
      paired SDs over the decade. These patterns demonstrate increasing inequity over
      the decade. The number of people sharing each GP was consistently and
      substantially lower in the capital city SDs and the Robin Hood Index values were
      consistently and substantially higher (overserved) compared with country SDs.
      CONCLUSIONS: Despite there being more GPs per capita in Australia, their
      distribution became increasingly unequal and inequitable between 1986 and 1996,
      such that rural and remote areas became increasingly poorly served.

PMID- 11297307
TI  - Application of the general health status questionnaire SF36 to patients with
      gastrointestinal dysfunction: initial validation and validation as a measure of
      change.
AB  - OBJECTIVE: To determine whether the Short Form (SF36) Health Status Survey is a
      valid measure of health status and health change for patients with irritable
      bowel syndrome (IBS). METHODS: The SF36 was self-administered by 116 patients
      with IBS at the commencement and end of a controlled clinical trial. Patients
      were recruited through two Sydney teaching hospitals and through private
      gastroenterologists during 1997 and treated with Chinese herbal medicine.
      RESULTS: The SF36 health concepts demonstrated internal consistency, construct
      validity and concurrent validity when applied to patients with significant bowel
      dysfunction. Patient scores on two health scales of the SF36 (bodily pain,
      general health) correlated significantly with the bowel symptom scores recorded
      by patients and gastroenterologists at the beginning and end of the trial period.
      Actively treated patients significantly improved their scores in four out of
      eight of the health scales of the SF36 and reported overall improvement compared
      with inactively treated patients. CONCLUSIONS: The SF36 is a valid measure of
      general health status in IBS patients, is sensitive to the presence of IBS, and
      is adequately sensitive to gastrointestinal change in IBS patients. IMPLICATIONS:
      While the SF36 general health measure is used by the Australian Bureau of
      Statistics and widely overseas, until recently no data have been available on the
      sensitivity of the SF36 to gastrointestinal dysfunction or numerous other
      disorders. The SF36 is not only sensitive to the presence of IBS, it also
      provides a useful adjunct to current methods of evaluating treatment outcomes for
      IBS, and potentially other disorders.

PMID- 11297308
TI  - A 'segmented' sex industry in New Zealand: sexual and personal safety of female
      sex workers.
AB  - OBJECTIVE: Assess differences in personal circumstances, risk exposure and risk
      taking among female sex workers in different sectors of the New Zealand sex
      industry in regard to issues of sexual safety, drug use, violence and coercion.
      METHOD: A cross-sectional survey of 303 female sex workers was carried out in
      Christchurch, New Zealand, May-September 1999. RESULTS: There was evidence of
      'segmentation': street workers were younger, had started work at a younger age
      and had less education than indoor workers. More street than indoor workers used
      money from sex work for drugs and used drugs at work. There was a high level of
      condom use but little 'negotiation' about them with clients. High levels of
      violent experiences were reported, but street workers reported more, and more
      extreme forms of, violence than indoor workers. IMPLICATIONS: Although knowledge
      of condom use and sexual safety appears generally high and women in both sectors
      report taking the initiative for safer sex, drug use, violence and coercion
      remain of concern. While sexual safety will need ongoing health promotion and
      education interventions to support and ensure the uptake of safer sex practice by
      new workers and prevent any relapse by more experienced workers, issues of
      violence and coercion also require attention to the power relationships between
      individuals. Legislation and policy directed at these issues should encourage the
      control women can exert over their work practice. Reducing exposure to personal
      risk may require different measures in different sectors.

PMID- 11297309
TI  - The health and welfare needs of female and transgender street sex workers in New
      South Wales.
AB  - OBJECTIVES: To determine the health and welfare status of female and transgender
      street sex workers and their work-related experiences. Also to estimate
      population numbers, determine work locations, and identify the most appropriate
      education, health and welfare services for this group. METHODS: Forty-eight
      street sex workers completed a questionnaire, mainly at their place of work.
      Demographic and sexual health profiles of sex workers attending the Sydney Sexual
      Health Centre and the Kirketon Road Centre in 1997 were compared with the street
      sample. RESULTS: Up to 120 female and transgender sex workers worked on the
      streets in Sydney, Newcastle, Wollongong and surrounding areas in any one night:
      more than 80% of these were female. Of those sampled, fewer street workers than
      brothel sex workers (6% vs. 41%; p<0.001) were from non-English speaking
      backgrounds, and more (77% vs. 7%; p<0.0001) were currently injecting drugs. The
      street workers reported lower rates of condom use at work than local brothel
      workers (91.7% vs. 98.8%; p<0.016) and high rates of hepatitis B and C infection.
      Seventy-five per cent had experienced violence at work. Child care, lack of
      supportive relationships, community intolerance and low self-esteem were
      important problems for the street workers. While the police were frequently
      required by the community to move the street workers on, there were no reports of
      corrupt behaviour by police. CONCLUSIONS: Health services need to specifically
      target this group with particular attention to the prevention of blood-borne
      virus infections, contraception, drug dependency and transgender issues.
      Consideration should be given to developing a network of safe houses to reduce
      community pressure and violence.

PMID- 11297310
TI  - Advocacy for clinical trials: do the Royal Colleges and State cancer councils
      play an appropriate role?
AB  - BACKGROUND: Endorsement of clinical trials by prominent local or national
      organisations may help to promote public awareness of and enhance patient and
      doctor participation in randomised trials. METHOD: A survey was undertaken of the
      specialist medical colleges of Australia, State and Territory cancer councils and
      national cancer organisations, inquiring about their formal position on patient
      participation in randomised clinical trials and any activities they undertake to
      promote clinical trial participation. RESULTS: Responses were received from 18 of
      20 organisations surveyed. The majority (13/18) support the idea that patients
      should be invited to participate in well-designed clinical trials. Only 9/18
      organisations have any formal policy encouraging clinical trial participation and
      only five undertake any activity to promote clinical trials. These activities
      relate more to facilitating clinician participation through affiliation with
      cooperative oncology groups/clinical trial organisations and provision of funds
      for data management. Only two organisations are proactive in promoting trials to
      clinicians and patients. CONCLUSION: Promoting/endorsing clinical trial
      participation is a priority area identified in the national cancer control plan
      and implementation strategy. Prominent organisations such as specialist medical
      colleges and State cancer councils should explore ways in which they can act as
      advocates to promote clinical trial participation.

PMID- 11297311
TI  - Second-hand smoke at work: the exposure, perceptions and attitudes of bar and
      restaurant workers to environmental tobacco smoke.
AB  - OBJECTIVES: To investigate the knowledge of, and perceptions, attitudes and
      exposure to second-hand smoke (SHS) of staff in the New Zealand hospitality
      industry. METHOD: Face-to-face interviews with bar staff, waiters, and bar and
      eating-place managers and owners in Wellington during the 1999-2000 summer. An
      analysis was made of the 1999 New Zealand Electoral Roll to find the number of
      those most exposed to SHS. RESULTS: 435 interviews with full data recovery were
      completed at 364 locations; 59% of interviewees were exposed to SHS, including
      77% of those at licensed premises. More than half of those exposed to workplace
      smoke reported irritation from SHS to their throat or lungs. Less than a third
      were aware of the risk of strokes from SHS. Three-quarters of interviewees wanted
      some sort of smoking restriction in bars. CONCLUSIONS: The majority of
      interviewees were at risk of premature death and disease because of exposure to
      workplace smoke, and had an incomplete knowledge of the dangers to which they
      were exposed. More than 5,000 similar workers in New Zealand appear to share this
      risk. IMPLICATIONS: This industry needs legislation to make it smoke free.

PMID- 11297312
TI  - The current hiatus in occupational injury research in Australia.
AB  - OBJECTIVE: In late 1999, the Safety Institute of Australia (SIA) noted the
      difficulty of accessing and reviewing Australian research into occupational
      injuries and asked for a register of research in this field to be created. It
      offered the use of its website as a continuing location for a possible register.
      The creation of the initial database was the primary objective of this work.
      METHOD: Data collection was by survey form, which was distributed by mail to
      relevant organisations and individuals and was also downloadable from the SIA
      website. Responses were accepted by mail, fax and e-mail. RESULTS: By April 2000,
      responses which included publications in peer-reviewed journals since 1995
      totalled just 154. This seemed to support the Institute's opinion that the amount
      of research in progress was inadequate to reduce the incidence of workplace
      injuries in Australia. CONCLUSIONS AND IMPLICATIONS: The small number of
      responses was partly due to the 1996 restructuring of the National Occupational
      Health and Safety Commission. Additionally, present arrangements give no role for
      investigator-initiated and investigator-driven research which has been the
      essential prerequisite for success in other areas of public health. The
      Australian workforce is now disadvantaged in contrast to overseas competitors who
      have national occupational injuries research organisations. To remedy this
      situation, a new science-based research grant organisation, with annual funds of
      about $25 million, administered by a new Occupational Injuries Research Council
      is proposed.

PMID- 11297313
TI  - The flood, The Hague and the mosquito.

PMID- 11297314
TI  - Ultrapath X: international resurgence of ultrastructural pathology.

PMID- 11297315
TI  - Ultrastructural features of solid/trabecular areas in differentiated thyroid
      carcinoma.
AB  - The presence of areas exhibiting a solid/trabecular pattern of growth within an
      otherwise differentiated thyroid carcinoma represents a source of controversy as
      regards its proper classification and biologic and prognostic significance. The
      aim of the current study was to investigate the ultrastructural features of
      solid/trabecular areas in differentiated thyroid carcinoma and to compare those
      features with the submicroscopic profile of differentiated, poorly differentiated
      (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The
      study series included differentiated carcinoma with solid/trabecular areas (3
      cases), conventional papillary carcinoma (4 cases), follicular variant of
      papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3
      cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that
      the solid/trabecular areas in differentiated carcinoma and poorly differentiated
      (insular) carcinoma share similar ultrastructural features and overall retain,
      even if attenuated, many of the submicroscopic attributes of differentiated
      carcinomas. In particular, nests of neoplastic cells were observed showing a
      highly developed cytosecretory apparatus and the presence of numerous
      abortive/rudimentary follicles, and intercellular and intracellular
      (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports
      the hypothesis that the solid/trabecular areas do not merely represent an
      architectural pattern but rather should be regarded as the expression of a
      process of reduced differentiation similar to that of poorly differentiated
      (insular) carcinoma.

PMID- 11297316
TI  - Angiomyolipoma: immunohistochemical and ultrastructural study of 14 cases.
AB  - Angiomyolipoma (AML) is a mesenchymal neoplasm of unclear histogenesis. In
      addition to varying amounts of smooth muscle, adipose tissue, and blood vessels,
      it contains a population of clear or pale eosinophilic epithelioid cells often
      arranged around blood vessels. Various phenotypes of AML have been described:
      leiomyoma-like, lipoma-like, epithelioid, and atypical. AMLs show consistent
      immunopositivity for HMB-45. This has been associated with the ultrastructural
      observation of melanosome-like structures in rare instances. In the present
      study, 14 AMLs from 13 patients were analyzed by electron microscopy and
      immunohistochemistry to determine the appearance and nature of cells composing
      AMLs. Overlap between cell types (spindle smooth muscle cells, epithelioid cells,
      and adipocytes) was found by both electron microscopy and immunohistochemistry.
      Melanosomes were found in 7 tumors. The cell of origin remains mysterious.
      Nevertheless, the study demonstrates that the AML is likely derived from a single
      cell that shares homology with the pericyte.

PMID- 11297317
TI  - Fibrosarcoma mimicking plasmacytoma or carcinoma: an ultrastructural study of 4
      cases.
AB  - Because the fibroblast has a remarkable capability of phenotypic modulations,
      reflected in both morphologic and immunohistochemical (IHC) changes,
      ultrastructural studies are mandatory to identify the variants of fibroblasts.
      Myofibroblasts or histiofibroblasts are such examples, demonstrating chimeric
      ultrastructural features of fibroblastic cells in common with smooth muscle cells
      or with histiocytes, respectively. The presence of epithelioid fibroblastic cells
      sharing morphologic features with epithelial or plasma cells has not been yet
      characterized. The authors identified 4 cases of fibrosarcomas (FS) characterized
      by an unusual phenotype and associated with peculiar ultrastructural findings.
      The electron microscopic (EM) findings were correlated with the histologic
      appearance and immunoprofile. All tumors were located in the extremities, 3 in
      soft tissues and 1 in the bone. By light microscopy 2 cases were composed
      predominantly by round uniform cells with a striking plasmacytoid appearance. One
      case mimicked carcinoma, composed predominantly by epithelioid cells and
      scattered giant tumor cells. The fourth case showed a mixture of plasmacytoid
      like and epithelioid cells. By IHC, tumor cells were positive for vimentin and in
      2 cases also for epithelial membrane antigen. Kappa/lambda light chain and
      cytokeratins markers were negative. By EM all 4 tumors showed in addition to
      classic features of fibroblasts, unusual epithelial-type features, such as
      secretory granules of "neurosecretory-type" (3 cases), rudimentary cell junctions
      (3 cases), microvilli (2 cases), and lumen-like structures (1 case). One
      plasmacytoid-type tumor showed finely granular extracellular deposits. The study
      describe 4 examples of fibrosarcomas with unusual features at the ultrastructural
      level, which are associated microscopically with a peculiar phenotype, mimicking
      plasmacytoma or carcinoma. These findings broaden the spectrum of fibroblastic
      cell variants in neoplasia.

PMID- 11297318
TI  - The myofibroblast: an assessment of controversial issues and a definition useful
      in diagnosis and research.
AB  - Some interpretational problems associated with the myofibroblast, which affect
      how this cell is identified, are discussed. Questions addressed include
      distinguishing between "external" lamina ("basement membrane") and the
      fibronectin fibril of the fibronexus; the nature of stress fibers (bundles of
      smooth-muscle myofilaments with focal densities); the utility of some of these
      features to distinguish between myofibroblastic and smooth-muscle cell surfaces;
      and cytoskeletal immunophenotype. The following points are emphasized.
      Myofibroblasts have a surface characterized by prominent fibronectin fibrils and
      fibronexus junctions, which are distinct from lamina ("basement membrane"). This
      can permit a distinction to be made between smooth-muscle and myofibroblastic
      lesions and tumors. Myofibroblasts are typically positive for vimentin and alpha
      smooth-muscle actin, but desmin is not a useful discriminant between smooth
      muscle and myofibroblastic lesions. The main features for defining the
      myofibroblast are abundant rough endoplasmic reticulum; modestly developed
      peripheral myofilaments with focal densities (stress fibers); fibronexus
      junctions; vimentin and smooth-muscle actin immunostaining. Other features
      include a Golgi apparatus and collagen secretion granules, gap junctions, and
      actin-associated nondesmosomal junctions. Illustrations of the usefulness of
      these criteria in the diagnosis of soft-tissue lesions (myofibrosarcoma, so
      called myofibroblastoma) are given.

PMID- 11297319
TI  - Ultrastructural heterogeneity of the alveolar macrophages from tobacco smokers
      with chronic bronchitis.
AB  - Alveolar macrophages recovered by bronchoalveolar lavage from 14 heavy smokers
      with chronic bronchitis were assessed. Ultrastructural examination revealed
      marked cellular heterogeneity. Three subpopulations of alveolar macrophages were
      readily identifiable. These have been termed "young," "mature," and "degrading,"
      reflecting their ultrastructural features. In addition, a majority of the cells
      were found to be positive by TUNEL staining, indicating DNA damage, but a very
      small percentage tested positive for Caspase-3, suggesting that apoptosis might
      not account for the DNA damage in at least some of these cells. A small
      percentage of proliferating cells were noted.

PMID- 11297320
TI  - Neuronal ceroid lipofuscinosis: an ultrastructural, genetic, and clinical study
      report.
AB  - The term "neuronal ceroid lipofuscinosis" (NCL) describes a complex of inherited
      neurodegenerative conditions associated with storage of lipopigments in brain
      tissue. In 1989 Dyken proposed a classification of NCL based on the age, clinical
      symptoms, and ultrastructural aspects of the lipopigments. At the ultrastructural
      level it is possible to distinguish 5 different patterns of osmiophilic
      lipopigments: usual lipofuscin, fingerprint deposits, granular profiles,
      curvilinear bodies, and microtubular aggregates. The concept that each
      ultrastructural pattern was the counterpart of a specific clinical type has been
      proved not to be true. Advances in molecular genetic techniques have allowed the
      identification of defective genes and their protein products in several NCL
      clinical forms. Ceroid lipofuscin deposits may be ultrastructurally observed not
      only in neuronal cells, but also in several other sites, such as trophoblastic
      cells, thus permitting prenatal diagnosis. In spite of recent advances in
      immunohistochemical identification of biochemical markers, the ultrastructural
      identification of lipofuscinic pigments remains the gold standard to identify
      NCL, together with clinical aspects and respective gene defects. This study
      describes the ultrastructural aspects observed in 8 cases of NCL syndromes (3
      juvenile, 3 infantile, 1 late infantile, and 1 congenital clinical form). In
      these patients, genetic analysis was also performed.

PMID- 11297321
TI  - Cerebellar liponeurocytoma: immunohistochemical and ultrastructural study of a
      case.
AB  - The clinical, histopathological, and ultrastructural features of a cerebellar
      liponeurocytoma are reported. The tumor, a 3-cm mass localized in the right
      cerebellar hemisphere, was resected from a 61-year-old man clinically presenting
      with symptoms of intracranial hypertension. The lesion was composed of small, in
      some areas closely packed, medulloblastoma-like cells with prominent areas of
      lipidization phenomena. Moreover, mitoses, cellular atypia, and numerous vascular
      structures were focally observed. Glial and neuronal differentiation was
      immunohistochemically noted (glial fibrillary acidic protein, synaptophysin,
      neurofilaments, and neuron-specific enolase positivity). The p53 oncoprotein was
      detected in the majority of neoplastic cells and a moderate proliferation
      activity, evaluated by Mib-1 antibody, was focally appreciated. Ultrastructural
      study did not show evident neuritic processes, synapses, or dense core
      neuroendocrine granules. This cerebellar tumor previously called lipidized
      medulloblastoma and recently renamed cerebellar liponeurocytoma is considered an
      adult neoplasm with excellent prognosis histologically presenting prominent
      lipidized areas and, at the immunohistochemical and ultrastructural level, both
      glial and neuronal differentiation. The present study provides the first
      description of a less differentiated and histologically more aggressive form of
      this unusual tumor.

PMID- 11297322
TI  - Neonatal syncytial giant cell hepatitis with paramyxoviral-like inclusions.
AB  - Syncytial giant cell hepatitis in the neonatal period has been associated with
      many different etiologic agents and may present initially as cholestasis.
      Infectious causes are most common and include: (1 ) generalized bacterial sepsis,
      (2) viral agents, (3) toxoplasmosis, (4) syphilis, (5) listeriosis, and (6)
      tuberculosis. Viral hepatitis may be due to cytomegalovirus, rubella virus,
      herpes simplex, HHV-6, varicella, coxsackievirus, echovirus, reovirus 3,
      parvovirus B19, HIV, enteroviruses, paramyxovirus, and hepatitis A, B, or C
      (rare). Giant cell hepatitis may result in fulminant liver failure with massive
      hepatocyte necrosis and severe liver dysfunction leading to death, resolution
      with severely compromised liver function, or liver transplantation. The authors
      report a 6-week-old male who had an unremarkable perinatal period, became
      jaundiced after developing diarrhea, and subsequently developed liver dysfunction
      with massively increased liver enzymes and a coagulopathy. Open wedge and core
      liver biopsies were performed to determine if the patient should be listed for
      liver transplantation. Giant cell hepatitis with a significant mixed lymphocytic
      and neutrophilic infiltrate was present on both the wedge and core biopsies. The
      residual 60% of hepatocytes had ballooning degeneration and many possessed
      pyknotic nuclei. The hepatocytes were arranged in a pseudoacinar pattern.
      Electron microscopy showed paramyxoviral-like inclusions in the giant cells,
      characterized as large inclusions with fine filamentous, beaded substructures (18
      20 nm). Paramyxoviridae are nonsegmented, negative-sense, single-stranded RNA
      viruses. This family is divided into the Paramyxovirinae subfamily containing
      respirovirus (Sendai virus, parainfluenza virus type 3), rubulavirus (mumps,
      parainfluenza virus type 2), and morbillivirus genera (measles); and
      Pneumovirinae subfamily (pneumovirus genus [respiratory syncytial virus]).
      Supportive care to determine if hepatic function resolves following the viral
      episode, liver transplantation with fulminant liver failure, and ongoing
      evaluation in those who recover to assess chronic liver disease are necessary.
      Ultrastructural evaluation may unmask the etiologic agent for hepatitis and
      direct therapy.

PMID- 11297323
TI  - Middle ear adenoma is an amphicrine tumor: why call it adenoma?
AB  - Middle ear adenoma (MEA) is a rare tumor postulated to take origin from the
      lining epithelium of the middle ear cavity. The authors report on a case of MEA
      arising in a 53-year old woman suffering from a sensation of fullness in her left
      ear, otalgia, and light left-sided hearing loss. Histopathologically, the lesion
      was composed of cuboidal and polygonal cells displaying a trabecular, tubulo
      glandular, and solid pattern of growth. Immunohistochemically, neoplastic cells
      diffusely stained with anti-vimentin antibodies and were focally positive for
      chromogranin A, neuron-specific enolase, lysozyme, and cytokeratins AE1/AE3. The
      majority of tumor cells showed weak and diffuse staining with both anti-PP and
      anti-ACTH antibodies and intense positivity with anti-glucagon and anti Leu-7
      antibodies. Ultrastructural investigation revealed both mucinous-glandular and
      neuroendocrine differentiation. The authors suggest that the appropriate
      terminology would be adeno-carcinoid or amphicrine tumor of the middle ear rather
      than "adenoma," a term that does not reflect its dual nature.

PMID- 11297324
TI  - Tracheomalacia in a neonate with kniest dysplasia: histopathologic and
      ultrastructural features.
AB  - Kniest dysplasia is an autosomal-dominant chondrodysplastic condition
      characterized by disproportionate dwarfism, short trunk, small pelvis,
      kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and
      craniofacial manifestations. The craniofacial abnormalities include
      tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal
      detachment, prominent eyes, and sensorineural hearing loss. Radiologic features
      include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral
      bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and
      short tubular bones with broad metaphyses and deformed large epiphyses. This form
      of chondrodysplasia is associated with mutations in type II collagen splicing
      sequences. Mutations have been identified in the COL2A1 (type II collagen) gene
      between exons 12 and 24. Type II collagen is the predominant structural protein
      in cartilage, and mutations in this collagen account for the Kniest dysplasia
      phenotype. Histopathologic and ultrastructural features of epiphyseal plate
      cartilage have been described, but tracheal cartilage in an affected neonate has
      not been examined. The authors report the histopathologic and ultrastructural
      findings of anterior tracheal cartilage from a 35-day-old female with suspected
      chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal
      cartilage was moderately cellular, but lacked cystic and myxoid changes in its
      matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some
      of these inclusions were diastase-resistant and were also highlighted on Alcian
      blue staining. Ultrastructural examination revealed chondrocytes with greatly
      dilated rough endoplasmic reticulum containing granular proteinaceous material.
      There were also frequent aggregates of typical glycogen. The defect in the COL2A1
      gene is secondary to mutations, especially at splice junctions, and this markedly
      disrupts triple helix formation. The mutated type II procollagen results in
      intracellular retention within the chondrocytes, as abundant granular
      proteinaceous material within the dilated RER. A relationship is known to exist
      between the proportion of mutated to normal type II collagen in the matrix and
      the severity of the phenotype. With low levels of normal type II collagen, the
      phenotypic manifestations become more severe, such as in achondrogenesis type II.
      Both the quantity and quality of type II collagen modulates the phenotypic
      expression of type II collagenopathies.

PMID- 11297325
TI  - Costs of drug-related morbidity and mortality: enormous and growing rapidly.

PMID- 11297326
TI  - Preventable medication errors: identifying and eliminating serious drug
      interactions.

PMID- 11297328
TI  - Pharmacy organizations 1902-1952.

PMID- 11297327
TI  - ORCA: OpeRational ClassificAtion of drug interactions.

PMID- 11297329
TI  - A medical mission to Little Tibet: notes from a pharmacy editor's diary.

PMID- 11297330
TI  - Pharmacy-based consulting on dietary supplements.

PMID- 11297331
TI  - Drug-related morbidity and mortality: updating the cost-of-illness model.
AB  - OBJECTIVE: To update the 1995 estimate of $76.6 billion for the annual cost of
      drug-related morbidity and mortality resulting from drug-related problems (DRPs)
      in the ambulatory setting in the United States to reflect current treatment
      patterns and costs. DESIGN: For this study, we employed the decision-analytic
      model developed by Johnson and Bootman. We used the model's original design and
      probability data, but used updated cost estimates derived from the current
      medical and pharmaceutical literature. Sensitivity analyses were performed on
      cost data and on probability estimates. SETTING: Ambulatory care environment in
      the United States in the year 2000. PATIENTS AND OTHER PARTICIPANTS: A
      hypothetical cohort of ambulatory patients. MAIN OUTCOME MEASURES: Average cost
      of health care resources needed to manage DRPs. RESULTS: As estimated using the
      decision-tree model, the mean cost for a treatment failure was $977. For a new
      medical problem, the mean cost was $1,105, and the cost of a combined treatment
      failure and resulting new medical problem was $1,488. Overall, the cost of drug
      related morbidity and mortality exceeded $177.4 billion in 2000. Hospital
      admissions accounted for nearly 70% ($121.5 billion) of total costs, followed by
      long-term-care admissions, which accounted for 18% ($32.8 billion). CONCLUSION:
      Since 1995, the costs associated with DRPs have more than doubled. Given the
      economic and medical burdens associated with DRPs, strategies for preventing drug
      related morbidity and mortality are urgently needed.

PMID- 11297332
TI  - Performance of community pharmacy drug interaction software.
AB  - OBJECTIVE: To evaluate the performance of computerized drug-drug interaction
      (DDI) software in identifying clinically important drug-drug interactions.
      DESIGN: One-time performance test of computer systems using a standard set of
      prescriptions. SETTING: Community pharmacies or central corporate locations with
      pharmacy terminals identical to those used in actual pharmacies. PARTICIPANTS:
      Chain and health maintenance organization (HMO) pharmacies with seven or more
      practice sites in Washington State. A total of nine different DDI software
      programs were installed in 516 community pharmacies represented by these chains
      and HMOs. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and
      negative predictive values of software in detecting 16 well-established DDIs
      contained within six fictitious patient profiles. RESULTS: The software systems
      failed to detect clinically relevant DDIs one-third of the time. Sensitivity of
      the software programs ranged from 0.44 to 0.88, with 1.00 being perfect;
      specificity ranged from 0.71 to 1.00; positive predictive value ranged from 0.67
      to 1.00; and negative predictive value ranged from 0.69 to 0.90. For software
      packages that were installed at different locations, between-installation
      differences were observed. CONCLUSION: The performance of most DDI-detecting
      software programs tested in this study was suboptimal. Improvement is needed to
      advance their contribution to detection of DDIs.

PMID- 11297333
TI  - A survey of selected Internet pharmacies in the United States.
AB  - OBJECTIVE: To determine whether differences in the provision of pharmacy services
      exist among different types of Internet pharmacies. DESIGN: Survey of selected
      pharmacies with a presence on the Internet. Data were abstracted onto a data
      collection form for further analysis. Data collection was limited to 3 weeks.
      SETTING: U.S.-based Internet pharmacies that allow patients to purchase
      prescription medications online. Pharmacies were identified using a metasearch
      engine with the search terms "Internet pharmacy" and "Internet pharmacist."
      INTERVENTION: Survey. MAIN OUTCOME MEASURES: Comparisons of availability of 10
      commonly used products representing a variety of product categories, prescription
      verification methods, and privacy issues; and determinations of site
      navigability, drug information and provider access, and payment methods. Sites
      were categorized as "chain pharmacy extensions," "mail order pharmacies,"
      "independent pharmacy extensions," and "online pharmacies." RESULTS: Thirty-three
      sites were reviewed. There was significant variation among the four types of
      pharmacies selling prescriptions over the Internet. Most pharmacies provided all
      of the drugs in the survey. Patients were required to provide their own
      prescription at 88% of the sites, and 75% of sites used mail or fax to verify
      prescription integrity. More than 50% of sites had privacy policies posted, and
      64% used cookies. Chain pharmacy extensions required completion of an average of
      10.2 pages to order drugs versus 2.4 to 4 pages for all other site types. Drug
      information was written at an eighth-grade reading level at 36% of the sites.
      More than two-thirds of the sites provided a toll-free telephone for a health
      care professional. Nearly 80% of the sites accepted health insurance, and 95%
      accepted credit cards; however, only 40% used a secure transmission mechanism for
      patient or payment information. CONCLUSION: Internet pharmacies provide varying
      levels of service. Policies regarding the use of the Internet for obtaining
      medications should focus on improving the privacy of consumer information and
      ensuring the secure transmission of financial information.

PMID- 11297334
TI  - Pharmacists' knowledge of and attitudes toward opioid pain medications in
      relation to federal and state policies.
AB  - OBJECTIVE: To assess Wisconsin pharmacists' knowledge of and attitudes toward the
      use of opioid analgesics in the management of chronic cancer and noncancer pain,
      and to explore the potential for these beliefs to interfere with pharmacist
      dispensing, the last link of the distribution chain of controlled substances to
      patients. DESIGN: Mail survey. SETTING: Urban and rural pharmacies, long-term
      care facilities, hospitals, and outpatient clinics in Wisconsin in 1998. PATIENTS
      OR OTHER PARTICIPANTS: Representative sample of Wisconsin pharmacists.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Responses to self-administered
      questionnaires. RESULTS: Although most respondents were knowledgeable about the
      issues addressed in this study, there were important exceptions. Not all
      pharmacists knew what constitutes legitimate dispensing practices for controlled
      substances under federal or state policy in emergencies or for patients with
      terminal illnesses, and many were unaware of the important distinctions among
      addiction, physical dependence, and tolerance. Many respondents did not view the
      chronic prescribing/dispensing of opioids for more than several months to
      patients with chronic pain of malignant or nonmalignant origin as a lawful and
      acceptable medical practice; this was especially true when the patient had a
      history of opioid abuse. CONCLUSION: Pharmacists play a pivotal role in ensuring
      patient access to medications. Viewed in the context of federal and state
      controlled substances policies, our findings suggest that the incorrect knowledge
      and inappropriate attitudes of some pharmacists could contribute to a failure to
      dispense valid prescriptions for opioid analgesics to patients in pain.

PMID- 11297335
TI  - Effects of estrogen on congnition mood, and degenerative brain diseases.
AB  - OBJECTIVE: To review research findings on the effects of estrogen on cognition,
      mood, memory, and degenerative brain disease in women. DATA SOURCES: English
      language journal articles published primarily since 1995, retrieved from a
      MEDLINE search and from bibliographies of selected reviews. STUDY SELECTION:
      Investigational studies, clinical trials, and review articles examining the
      effects of estrogen on the central nervous system. DATA SYNTHESIS: Although
      scientific study of the brain is in its infancy, numerous studies indicate that
      estrogen is essential to optimal brain function. Estrogen has been shown to
      increase cerebral blood flow, act as an antiinflammatory agent, enhance activity
      at neuronal synapses, and exert direct neuroprotective and neurotrophic effects
      on brain tissue. Through these varied mechanisms, estrogen strongly influences
      mood and cognition, and the decline of this hormone at menopause can produce
      significant emotional and cognitive problems in women. CONCLUSION: Pharmacists
      can educate women about the various mood and memory changes that can occur during
      perimenopause and how estrogen replacement therapy may lead to improvements in
      brain function. The potential use of estrogen replacement therapy to reduce the
      risk of Alzheimer's disease and ease the symptoms of Parkinson's disease could
      have a profound effect on women, their families, and society as a whole.

PMID- 11297336
TI  - New drugs of 2000.
AB  - OBJECTIVE: To provide information regarding the most important properties of the
      new therapeutic agents marketed in 2000. DATA SOURCES: Published studies, drug
      information reference sources, and product labeling. DATA SYNTHESIS: In 2000, 33
      new therapeutic agents were marketed. The indications and information on dosage
      and administration for the new agents are reviewed, as are the most important
      pharmacokinetic properties, adverse events, drug interactions, and other
      precautions. Practical considerations for the use of the new agents are also
      discussed. Where possible, the properties of the new drugs are compared with
      those of older drugs marketed for the same indications. CONCLUSION: A number of
      the new therapeutic agents marketed in 2000 have important advantages over older
      medications. An understanding of the properties of these agents is important if
      the pharmacist is to effectively counsel patients about their use and to serve as
      a valuable source of information for other health care professionals regarding
      these drugs.

PMID- 11297337
TI  - New OTC drugs and devices 2000: a selective review.
AB  - OBJECTIVES: To create a heightened awareness of the issues confronting
      pharmacists in the self-care arena. To educate pharmacists about newly introduced
      nonprescription products, devices, and diagnostic products. DATA SOURCES:
      Recently published governmental, clinical, and pharmaceutical industry
      literature. DATA SYNTHESIS: Several developments during the previous year have
      important implications for patient self-care. The Food and Drug Administration
      recommended the withdrawal of phenylpropanolamine from the market and denied
      proposals to switch lovastatin, pravastatin, and omeprazole to nonprescription
      status. Widespread use of dietary supplements in the face of insufficient data on
      their safety and efficacy continued to be a problem in 2000, although there were
      several encouraging developments. In 2000, new over-the-counter products were
      introduced for, among other purposes, treating acid-peptic disorders,
      musculoskeletal injuries, dermatologic disorders, and minor wounds. Numerous
      nonprescription products, including sophisticated home diagnostic products and
      accessories, continue to become available on the U.S. market. It is important
      that the pharmacist become as knowledgeable as possible about these products so
      he or she can educate patients about their appropriate use. CONCLUSION: Patients
      will continue to place an increasing emphasis on self-care. To assist them,
      pharmacists must remain up to date on trends and have a balanced understanding of
      new products. The new nonprescription medications and diagnostic products
      discussed in this review article represent valuable additions to the growing
      array of self-care products.

PMID- 11297338
TI  - An educational intervention about folic acid and healthy pregnancies targeted at
      college-age women.

PMID- 11297339
TI  - Compatibility of linezolid injection with intravenous administration sets.

PMID- 11297340
TI  - Putting our best foot forward: the pharmacist's role in preventing diabetic foot
      ulcers.

PMID- 11297341
TI  - Pharmacists can look to national effort for help in improving patient safety.

PMID- 11297342
TI  - Vaccination roles for pharmacy students and pharmacy technicians.

PMID- 11297343
TI  - Ceplene encounters obstacles on the rocky road to FDA approval.

PMID- 11297344
TI  - Cruising the Internet at work: is big brother watching you?

PMID- 11297346
TI  - Cu(OBt)2 and Cu(OAt)2, copper(II)-based racemization suppressors ready for use in
      fully automated solid-phase peptide synthesis.
AB  - The complexes Cu(OBt)2 and Cu(OAt)2, which are derived from copper(II) and HOBt
      and HOAt, respectively, are shown to be more effective in suppressing
      racemization during solid-phase peptide synthesis (SPPS) than are those compounds
      currently being used for this purpose. These compounds can readily be used in
      conjunction with the commonly applied coupling reagents in fully automated
      systems for solid-phase peptide chemistry.

PMID- 11297348
TI  - Highly potent side-chain to side-chain cyclized enkephalin analogues containing a
      carbonyl bridge: synthesis, biology and conformation.
AB  - Six novel cyclic enkephalin analogues have been synthesized. Cyclization of the
      linear peptides containing basic amino acid residues in position 2 and 5 was
      achieved by treatment with bis(4-nitrophenyl)carbonate. It was found that some of
      the compounds exibit unusually high mu-opioid activity in the guinea pig ileum
      (GPI) assay. The 18-membered analogue cyclo(N(epsilon),N(beta)-carbonyl-D
      Lys2,Dap5)-enkephalinamide turned out to be one of the most potent mu-agonists
      reported so far. NMR spectra of the peptides were recorded and structural
      parameters were determined. The conformational space was exhaustively examined
      for each of them using the electrostatically driven Monte Carlo method. Each
      peptide was finally described as an ensemble of conformations. A model of the
      bioactive conformation of this class of opioid peptides was proposed.

PMID- 11297347
TI  - Influence of thermal motion on 1H chemical shifts in proteins: the case of bovine
      pancreatic trypsin inhibitor.
AB  - The possible influence of thermal motion on 1H chemical shifts is discussed for a
      small stable protein, the bovine pancreatic Kunitz trypsin inhibitor (BPTI). The
      thermal effects on the aromatic side chains and on the backbone are treated
      separately. The thermal motion of the aromatic side chains is accounted for in
      terms of their rotation around the C(alpha)-C(beta) bond and the motion of each
      individual proton is interpreted as a ratio between the amount of ordered and
      quite disordered states. The influence of hydrogen bonds is introduced as an
      extra contribution to the chemical shifts of the bonded proton. Their
      contribution to the chemical shifts resulting from the polarization of the
      peptide bond is investigated, as is their influence on local flexibility.
      Finally, the relative importance of each contribution to the chemical shift
      information is compared.

PMID- 11297350
TI  - Protein design and folding: template trapping of self-assembled helical bundles.
AB  - An experimental system is described, permitting a detailed and systematic
      analysis of the factors governing self-assembly of amphipathic helices, e.g. to a
      four-helical bundle, a subject of major relevance for tertiary structure
      formation, protein folding and design. Following the Template Assembled Synthetic
      Proteins (TASP) approach, helices of different packing potential are
      competitively assembled in solution with a preformed two-helix TASP molecule, and
      after equilibration are covalently attached ('template trapping') via
      chemoselective thioether formation. The quantitative analysis of the individual
      TASP molecules by high performance liquid chromatography (HPLC) and electrospray
      mass spectrometry (ES-MS) allows the delineation of the role of complementary
      packing in helix bundle formation. The procedure established represents a general
      tool for the experimental verification of modern concepts in molecular
      recognition.

PMID- 11297349
TI  - Synthesis of tetrapeptide p-nitrophenylanilides containing dehydroalanine and
      dehydrophenylalanine and their influence on cathepsin C activity.
AB  - Three dehydrotetrapeptides of rationally varying structure were prepared and
      tested as affectors of cathepsin C. These compounds appeared to be substrates of
      the enzyme, being equipotent with their classical counterparts. Thus, replacement
      of amino acid in a short peptide by corresponding dehydroamino acid does not
      prevent cathepsin C in recognizing dehydropeptide as its substrate.

PMID- 11297351
TI  - Properties and applications of the (2-nitrofluoren-9-yl)methoxycarbonyl group.
AB  - This paper presents a new protecting group, the (2-nitrofluoren-9
      yl)methoxycarbonyl group. Investigations on the properties of this new
      modification of the Fmoc-system, such as the solvent-dependent photochemical
      cleavage, and enhanced lability towards bases, are described, as well as UV
      kinetic measurements of the cleavage reaction. In addition, the incorporation of
      the (2-nitrofluoren-9-yl)methoxycarbonyl group into two peptides, and a sequence
      dependent photochemical cleavage reaction are reported.

PMID- 11297352
TI  - Synthesis and antigenic properties of reduced peptide bond analogues of an
      immunodominant epitope of the melanoma MART-1 protein.
AB  - Backbone modifications have been introduced into the melanoma derived peptide
      MART-1(27-35) to increase its binding to class I major histocompatibility complex
      HLA-A2 molecule, and ultimately to enhance its immunogenicity. Each analogue was
      obtained by replacing one peptide bond at a time in the natural epitope by the
      aminomethylene (CH2-NH) surrogate. All analogues displayed an increased
      resistance to proteolysis. Interestingly, the comparative results showed that
      five analogues bound more efficiently to HLA-A2 than the parent peptide. On the
      other hand, two pseudopeptide/HLA-A2 complexes were recognized by one melanoma
      specific T cell clone. Close examination of the impact of such modifications at
      the molecular level provides useful supports for the rational design of stable
      compounds with applications in anti-tumour specific immunotherapy and in vaccine
      development.

PMID- 11297353
TI  - Tryptic hydrolysis of hGH-RH(1-29)-NH2 analogues containing Lys or Orn in
      positions 12 and 21.
AB  - Two analogues of the 29 amino acid sequence of human growth hormone-releasing
      hormone, namely [Nle27]hGH-RH(1-29)-NH2 and [Orn(12,21),Nle27]hGH-RH(1-29)-NH2,
      have been synthesized and subjected to digestion by trypsin. The course of
      degradation was followed using RP-HPLC and ESI-MS. Several intermediates and
      final products of degradation were identified and conclusions regarding the rate
      of cleavages at different positions occupied by Lys and Arg residues were drawn.
      The analogue containing ornithine was found to be less susceptible to hydrolysis
      by trypsin: the 12-13 and 21-22 peptide bonds were completely resistant to the
      cleavage. The results show that by replacing Lys with Orn, a possibility exists
      to design new peptides, which could be more stable in biological fluids.

PMID- 11297354
TI  - Effect of nutritional and environmental conditions on the production and
      composition of rhamnolipids by P. aeruginosa UG2.
AB  - The production of rhamnolipid biosurfactants by P. aeruginosa UG2 was examined
      under different culture conditions. Rhamnolipid yield was affected by the nature
      of the carbon sources, the nutrient concentrations, pH, and age of the culture.
      Hydrophobic substrates like corn oil, lard (rich in unsaturated and saturated
      fat), and long chain alcohols maximized biosurfactant production (100-165 mg/g
      substrate). Hydrophilic substrates like glucose, and succinic acid delivered poor
      yields (12-36 mg/g substrate). Rhamnolipid production was greater when N as
      (NH4)(2)SO4 and trace metals were added in several periodic doses rather than at
      the beginning of the process. Increased biosurfactant production was seen in
      cultures maintained at neutral pH relative to cultures allowed to develop acidic
      conditions (pH = 6.25). Although the level of rhamnolipid production was affected
      by culture conditions, the distribution of rhamnolipid subspecies did not vary
      between cultures. A dirhamnolipid species containing two 10 carbon alpha-hydroxy
      fatty acids [Rh2C10C10] was the most abundant in the mixtures (60.6 mol%), while
      the levels of the monorhamnolipid [RhC10C10] (20.7 mol%) and two dirhamnolipids
      [Rh2C10C12 and its dehydro variant Rh2C10C12-H2] (18.7 mol%) were similar.
      Biosurfactant mixtures produced with corn oil as sole carbon source solubilized
      the herbicide trifluralin [2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzamine]
      to a greater extent. This suggests that the presence of incompletely metabolized
      hydrophobic by-products acting as co-solvents can increase the solubilization
      capacity of biosurfactant mixtures.

PMID- 11297355
TI  - Influence of temperature on flavour compound production from citrate by
      Lactobacillus rhamnosus ATCC 7469.
AB  - The citrate utilization by Lactobacillus rhamnosus ATCC 7469 was found to be
      temperature-dependent. The maximum citrate utilization and incorporation of [1,5
      14C]citrate rate were observed at 37 degreesC. At this temperature, maximum
      citrate lyase activity and specific diacetyl and acetoin production (Y(DA%)) were
      observed. The high levels of alpha-acetolactate synthase and low levels of
      diacetyl reductase, acetoin reductase and L-lactate dehydrogenase found at 37
      degreesC led to an accumulation of diacetyl and acetoin. Optimum lactic acid
      production was observed at 45 degreesC, according to the high lactate
      dehydrogenase activity. The NADH oxidase activity increased with increasing
      culture temperature from 22 degreesC to 37 degreesC. Thus there are greater
      quantities of pyruvate available for the production of alpha-acetolactate,
      diacetyl and aceotin, and less diacetyl and acetoin are reduced.

PMID- 11297356
TI  - Influence of iron on growth, production of siderophore compounds, membrane
      proteins, and lipase activity in Acinetobacter calcoaceticus BD 413.
AB  - Acinetobacter calcoaceticus BD413 was examined for production of siderophores and
      iron-repressible outer membrane proteins following growth in iron-restricted
      media. The iron-scavenging phenotype was associated with the secretion of iron
      repressible catechol and the induction of a group of six outer membrane proteins
      with molecular weights ranging from 34 to 85 kDa. The amount of catechol produced
      was dependent on medium composition and iron stringency. The relation between
      iron limitation and lipase production was studied at the level of lipA
      transcription and extracellular lipase activity. In minimal medium, iron
      limitation slightly affected lipA expression but decreased exo-lipase activity
      significantly. However, if iron limitation and rich nitrogen sources were
      simultaneously present in the culture media, the production of lipase was
      increased approximately 4 times.

PMID- 11297357
TI  - Detection and characterization of quorum sensing signal molecules in
      Acinetobacter strains.
AB  - Quorum sensing is a widespread regulatory mechanism among Gram-negative bacteria.
      In this study, Acinetobacter strains were assayed for the presence of quorum
      sensing signal molecules capable of activating N-acylhomoserine lactone
      biosensors. By using an Agrobacterium tumefaciens reporter strain it was shown
      that all the cultures produced two to four detectable signal molecules with
      different chromatographic patterns. In A. calcoaceticus BD413 supernatants four
      compounds were detected in a time-dependent manner, and maximal activity was
      reached at stationary phase. The number of signal molecules was dependent on
      medium composition; typically, cultures in minimal medium displayed one or two
      more signals, as compared to complex medium. None of the Acinetobacter
      supematants showed autoinduction activity with an Chromobacterium violaceum
      reporter strain, neither in direct or competition assays.

PMID- 11297358
TI  - Molecular and morphological characterization of Tuber magnatum mycorrhizas in a
      long-term survey.
AB  - Tuber magnatum Pico is an ectomycorrhizal fungus whose mycorrhizas can be barely
      distinguished morphologically from those of other related white truffles. Here we
      describe the use of specific primers based on the T. magnatum ITS sequence for
      screening mycorrhizas from a large number of growth chambers, greenhouse and
      nursery samples taken in a long-term survey. This molecular identification
      technique enabled a new morphological characterization to be set up for T.
      magnatum mycorrhizas.

PMID- 11297359
TI  - Microbial reaction to soil contamination with Cd(II) at different temperatures.
AB  - The response of the indigenous bacterial community to the addition of single
      doses of Cd(II) was studied in a sandy-loam soil at 6, 20 or 30 degreesC. Soil
      pollution significantly reduced the number of bacteria growing on 0.1% tryptic
      soy agar (TSA) and those growing on 0.01% TSA especially at 30 degreesC shortly
      after the addition of the metal. However, an increase in cfu numbers and
      dominance values of metal-tolerant populations were observed at this temperature
      with time. In addition, changes in the kinetics of colony development were found
      over the period of study.

PMID- 11297360
TI  - Isolation and characterization of actinomycetes from Brazilian tropical soils.
AB  - Actinomycetes have been isolated from three Brazilian tropical soils. The
      dispersion and differential centrifugation procedure revealed count values 1.5 to
      5.0 times greater than those obtained by the conventional dilution plate
      technique for all soils and media tested. Eighteen strains, promising for
      biotechnological applications, were submitted to chemotaxonomic procedures and
      numerical taxonomy for identification. Two were identified as Amycolatopsis
      orientalis, one as Streptomyces misakiensis, and two tentatively included or
      associated to S. chromofuscus and S. griseoruber. The others, all belonging to
      the Streptomyces genus, could not be fitted into any known species, and were
      arranged by the UPGMA analysis for classification, as an isolated group. This
      suggests that the actinomycetes in tropical soils may represent a vast unexplored
      resource for biotechnology.

PMID- 11297361
TI  - Vitamin requirements of hydrocarbon-utilizing soil bacteria.
AB  - The numbers of oil-utilizing bacteria in several samples of clean and oil
      polluted soils counted on vitamin-containing media were severalfold higher than
      the numbers counted on vitamin-free media. Colonies that grew on a medium
      containing a vitamin mixture were tested for growth on the same medium lacking
      any vitamins. More than 90% of the total colonies failed to grow. The remaining
      10% grew, yet their growth was enhanced, when vitamins were added. The
      predominant oil-utilizing bacteria in one of the test desert soil samples were
      various strains of Cellulomonas flavigena and Rhodococcus erythropolis. Minor
      organisms belonged to the genera Pseudomonas, Bacillus and Arthrobacter. Two
      vitamin-requiring biovars of C. flavigena and R. erythropolis were selected for
      further study. Their growth on n-octadecane and phenanthrene as sole sources of
      carbon and energy as well as their potential for hydrocarbon consumption were
      enhanced by added vitamins, e.g. folic acid, pyridoxine, vitamin B12, biotin and
      others. In a field experiment, it was confirmed that vitamin fertilization of an
      oil-polluted sand sample enhanced the biodegradation of constituent hydrocarbons
      of that sample.

PMID- 11297362
TI  - Antifungal activity of chitinases produced by some fluorescent pseudomonads
      against Colletotrichum falcatum Went causing red rot disease in sugarcane.
AB  - Chitinase production and growth of certain fluorescent pseudomonads isolated from
      sugarcane rhizosphere on different subtrates were studied. When chitin was
      substituted for glycerol in King's B medium, 3 of the 4 strains showed enhanced
      bacterial multiplication. Bacterial cells grown on chitin-containing medium
      showed enhanced antifungal activity against Colletotrichum falcatum Went causing
      red rot disease in sugarcane. Chitinase production was significantly higher when
      chitin was amended to King's B medium. Higher chitinase production was also
      recorded when fluorescent pseudomonad strains were grown in the medium containing
      crab-shell chitin. Cell-free bacterial culture filtrate from chitin-containing
      medium significantly inhibited mycelial growth of the pathogen. These cell-free
      conditioned media contained 3 to 7 polypeptides. Western blot analysis revealed
      five isoforms of chitinase with molecular masses of 47, 36, 32, 20 and 18.5 kDa.
      A possible role of chitinases in red rot disease management is discussed.

PMID- 11297363
TI  - Production of an antifungal antibiotic by Streptomyces aburaviensis 1DA-28.
AB  - A broad-spectrum antifungal Streptomyces isolate, 1DA-28, from Indian soil has
      been characterized and identified as Streptomyces aburaviensis var.
      ablastmyceticus (MTCC 2469). Nutritional and cultural conditions for the
      production of antibiotic by this organism under shake-flask conditions have been
      determined. Antibiotic production in synthetic medium reached the maximum on the
      5th day of incubation at 30 degreesC. Glucose and starch were found to be the
      best carbon sources while NH4NO3 was preferred as nitrogen source. Optimum
      temperature and pH for antibiotic production were 32 degreesC and 7.4,
      respectively. Phosphate at a concentration sub-optimal for growth enhanced
      antibiotic production. Supplementation of medium with casein hydrolysate improved
      both growth and antibiotic titre but yeast extract exhibited marked inhibition.

PMID- 11297364
TI  - Symbiotic effectiveness of spontaneous antibiotic-resistant mutants of Rhizobium
      sp. Cicer nodulating chickpea (Cicer arietinum).
AB  - Spontaneous streptomycin-resistant mutants were isolated from two fast growing
      gum-producing strains Ca85 and Ca401 and from two moderately growing strains
      Ca181 and Ca534 of Rhizobium sp. Cicer. The nodulation ability and symbiotic
      effectiveness of the mutants relative to parent strains were evaluated on
      chickpea (Cicer arietinum) grown in sterilized chillum jars. Some mutants of
      strains Ca85 and Ca401 showed Nod phenotype whereas some mutants of strains Ca181
      and Ca534 showed Nod(+) fix(-) phenotype. Other mutants also showed decreased
      nodule number and reduction in nitrogenase activity as well as in shoot dry
      weight as compared to inoculation with parental strains. The results showed that
      acquisition of streptomycin resistance in Rhizobium sp. Cicer strains is
      associated with decreased symbiotic effectiveness in chickpea, suggesting that
      antibiotic-resistant mutants first should be analyzed for symbiotic effectiveness
      before using these mutants for ecological studies or nodulation competitiveness.

PMID- 11297365
TI  - Cell-mediated immune response to high-passage Borrelia spirochetes in C57bl/6
      mice is strictly dependent on antigen specificity.
AB  - Inbred C57bl/6 mice were challenged with high-passage Borrelia afzelii, Borrelia
      garinii and Borrelia burgdorferi sensu stricto and tested for antigen specific T
      cell response in vitro. Sonicated preparations of washed spirochetes were potent
      cell activators, capable of stimulating polyclonal proliferation after 72h of
      culture while increasing the incubation time up to 120h provoked specific cell
      mediated response. Isolated murine spleocytes previously sensitized to B.
      burgdorferi sensu lato but not those from control mice could be induced for
      antigen-specific proliferation in vitro, as revealed by [3H]thymidine
      incorporation assay, Moreover, in mice presensitized to B. burgdorferi sensu
      lato, detectable cell-mediated response could be induced only with antigen
      preparations derived from a corresponding strain but not with those obtained from
      other Borrelia genospecies. The current study emphasises that the B. burgdorferi
      antigen-specific response may also be expected in different genospecies
      infections in men.

PMID- 11297367
TI  - Isolation and characterization of methicillin-resistant Staphylococcus aureus
      strains from nares of nurses and their gowns.
AB  - The isolation and characterization of methicillin-resistant Staphylococcus aures
      (MRSA) strains from the bilateral nares of nurses and their gowns are described.
      MRSA strains could be isolated from eigth of fifty bilateral nares of nurses and
      two of their gowns. Ten MRSA strains were typed using coagulase typing, and
      divided into two types, coagulase II and III. In this study, we found a new group
      (producing toxic shock syndrome toxin -1, coagulase III and staphylococcal
      enterotoxin C) in Japanese MRSA. Furthermore, we confirmed that MRSA strains
      originating from bilateral nares of three nurses were identical and two strains
      isolated from the left naris of one nurse and her gown were also identical by
      pulsed-field gel electrophoresis.

PMID- 11297366
TI  - Characterization of hemolytic activity of Staphylococcus aureus strains isolated
      from bovine mastitic milk.
AB  - Beta (beta) and delta (delta)-hemolysin of Staphylococcus aureus strains were
      cultured in vitro in milk lactoserum (whey) prepared from both healthy and
      mastitis bovine milk. Production of beta- and delta-hemolysins were detected in
      12 out of 50 strains studied. The association between N-acetyl-beta-D
      glucosaminidase (NAGase) activity, plasmin activity (PL) and trypsin inhibitory
      capacity (TIC), known as inflammatory indicators for mastitis, and hemolytic
      activity were also studied. Mastitic milk decreased directly the lytic effect of
      both beta-and delta-hemolysins of S. aureus on hemolytical blood agar plates. S.
      aureus in healthy milk samples produced more beta-hemolysin (3 times) and delta
      hemolysin (2 times) when compared to S. aureus supernatants in milk from infected
      quarters. Furthermore, beta- and delta-hemolysis correlated negatively with TIC
      and NAGase and PL activities. Addition of reduced glutathione (GSH) or beta
      mercaptoethanol into the artificial medium enhanced hemolysins activity.

PMID- 11297368
TI  - Differential viable count of mixed starter cultures of lactic acid bacteria in
      doughs by using modified Chalmers medium.
AB  - The modified Chalmers medium appeared as quite suitable for counting a mixed
      population consisting of different species of lactic acid bacteria used as
      starter in breadmaking. Selected strains of Lactobacillus plantarum, Leuconostoc
      mesenteroides subsp. mesenteroides, Lactobacillus sanfranciscensis, Enterococcus
      faecalis together with Saccharomyces cerevisiae could be easily differentiated
      and counted with an acceptable recovery in comparison with reference media.

PMID- 11297369
TI  - Giant-cell fibroblastoma: a case report emphasising the presence of hyperplastic
      subplasmalemmal linear densities in continuity with granular matrices in the
      extracellular space.
AB  - The histological, immunohistochemical and ultrastructural features of a case of
      giant-cell fibroblastoma from the soft tissues of the chest wall in a 48-year-old
      female are described with special reference to the cell surface and matrix.
      Subplasmalemmal linear densities (SLDs) characterised cell surfaces, and
      exhibited excessive development of the dense external component: foci of
      identical dense material were present in the matrix. The nature of these dense
      foci, both the external component of the SLD and those free in the extracellular
      space, was investigated by light microscope immunostaining for fibronectin,
      laminin and collagen IV. All three proteins stained vessels. There was weaker but
      positive staining for tumour cell surfaces and matrix, consistent with the widely
      dispersed nature of the dense foci. Given their fine structural appearance, these
      dense foci can be referred to as granular matrices. Given also that the matrix
      protein immunostaining pattern is consistent with the distribution of these
      granular matrices as observed by electron microscopy, they may be provisionally
      interpreted as a kind of basement-membrane-related granular matrix. The presence
      of these proteins emphasises the point that, while giant-cell fibroblastoma
      fibroblasts lack a lamina, they nevertheless bear basement-membrane-related
      proteins organised, however, in a non-laminate fashion. The observations
      reinforce the need to qualify immunostaining results by ultrastructural
      investigation in order to understand the organisation of immuno-detected proteins
      and are discussed in terms of their diagnostic and possible biological
      significance.

PMID- 11297371
TI  - GM-CSF expression by tumor cells correlates with aggressivity and with stroma
      reaction formation.
AB  - Granulation tissue involved in tissue repair and in the stroma reaction to
      epithelial tumors is characterized by the presence of myofibroblastic cells. It
      has been previously reported that granulocyte macrophage-colony stimulating
      factor (GM-CSF) induces a fibrotic reaction containing numerous myofibroblasts.
      This reaction results from a cascade of events, including stimulation of
      transforming growth factor-beta1 (TGF-beta1) production by macrophages which, in
      turn, promotes alpha-smooth muscle actin and collagen synthesis by fibroblasts.
      Moreover, GM-CSF is known to be expressed by many tumor cell types. In this study
      we have analyzed, by means of reverse transcription-polymerase chain reaction, GM
      CSF mRNA expression in a progressive and a regressive rat colon carcinomas and in
      the corresponding cell lines, eliciting different degrees of desmoplastic
      reaction. We have also evaluated the expression of GM-CSF protein in selected
      cases. The expression of GM-CSF mRNA and, when tested, protein were higher in
      progressive compared to regressive cancer cells both in vivo and in vitro. We
      then investigated GM-CSF mRNA and protein expression in different human colon
      cancer cell lines known to exhibit different degrees of aggressivity in vivo. We
      found high levels of GM-CSF mRNA and protein in the most aggressive cell lines.
      Similar results were also obtained on human breast and cervical cancer cell
      lines. Our results are in agreement with the assumption that GM-CSF expression is
      correlated to tumor aggressivity. Conceivably, one of the GM-CSF actions
      affecting tumor progression is exerted through its influence on stroma reaction
      development.

PMID- 11297370
TI  - Basement-membrane-related peri-vascular matrices not organised as a basal lamina:
      distribution in malignant tumours and benign lesions.
AB  - Peri-vascular matrices having a finely textured granular substructure have been
      identified in 27 human lesions: these were mostly malignancies but included
      benign tumours and reactive processes. The matrices were defined as stromal
      components surrounding endothelium and pericytes, and lying between vessels and
      adjacent lesional cells. They were identified as having a finely textured,
      uniform and moderately dense substructure, and differed from a conventional basal
      lamina expected at these sites by the absence of the typical lamina densa/lamina
      lucida configuration. By light microscope immunohistochemistry, vessels stained
      positively for laminin and collagen IV, two of the main proteins characterising a
      conventional basal lamina. The present observations emphasise the following. 1)
      The proteins laminin and collagen IV can be found in peri-vascular locations
      which have a finely textured granular substructure, and which have clearly
      defined ultrastructural differences from a conventional basal lamina. 2) While
      conventional light microscope immunohistochemistry demonstrates the presence and
      cellular location of proteins, electron microscopy is helpful for giving
      information on their physical organisation. 3) Peri-vascular granular matrices
      have a widespread distribution in malignant tumours but also exist in benign
      tumours and reactive lesions. This paper briefly discusses the possible functions
      of these matrices as modulators of cell biological processes.

PMID- 11297372
TI  - Morphological phenotypes in neoplastic progression of benz(alpha)pyrene-treated
      breast epithelial cells.
AB  - The neoplastic conversion of a normal cell to a malignant one is a multistage
      process that occurs after a series of molecular alterations. Several chemical and
      physical agents can alter the morphology of different types of cells. Scanning
      and transmission electron microscopy have been valuable in evaluating changes
      that occur in the progression of transformation. MCF-10F, a spontaneously
      immortalized human breast epithelial cell line (Soule et al., 1990), was treated
      with benz(alpha)pyrene (BP) (Calaf and Russo, 1993) and then transfected with the
      c-Ha-ras oncogene (Calaf et al., 1995). The phenotypic changes of breast cancer
      progression were studied through the use of scanning and transmission electron
      microscopy. Activated oncogenes have been detected in a variety of malignant
      tumors and the altered expression of certain genes seems to play a role in the
      cancer process. Carcinogen-treated and transfected cells showed a progression of
      changes in the morphology, anchorage independent growth, invasiveness and
      capability of tumor formation in the SCID mice. This in vitro cancer model can
      parallel the progression of breast cancer seen through molecular changes that
      occur and have been observed during the natural development of this disease.

PMID- 11297373
TI  - Ultrastructural and cytochemical studies of the spermatozoa of Acrosternum
      aseadum (Hemiptera: Pentatomidae) after copulation.
AB  - Beside the morphofunctional modifications undergone during spermiogenesis, the
      spermatozoon could undergo other modifications after copulation. Since no
      structural modification occurs in the spermatozoon of Acrosternum aseadum after
      copulation, we used cytochemical studies to show the enzymatic activities
      variations of acid phosphatase, thiamine pyrophosphatase, glucose-6-phosphatase
      and cytochrome C oxidase, when the spermatozoon passes through the spermatheca.
      The enzymatic activity, few hours after copulation, is strong and specifically
      located. However, 40 h after copulation, there is considerable loss of enzymatic
      activity, with the exception of thiamine pyrophosphatase, which shows the same
      activity. This result indicates that the spermatozoon of A. aseadum undergoes
      physiological modifications when passing through the spermatheca and that these
      modifications may be involved with survival in this organ as well as with the
      fertilization process.

PMID- 11297374
TI  - Putative commissural and collicular axo-somatic terminals on neurons of the rat
      ventral cochlear nucleus.
AB  - The type of synaptic terminals from the cochlear nucleus and inferior colliculus
      that terminate in the contralateral ventral cochlear nucleus are not known. These
      terminals were studied with the electron microscope and immunogold after
      injection of wheat germ agglutinin conjugated to horseradish peroxidase into the
      inferior colliculus or into the cochlear nucleus. The tracer anterogradely
      labelled boutons onto the main neurons of the contralateral ventral cochlear
      nucleus. Most of these cells (95%) were glycine immuno-negative and represent
      excitatory neurons. After injection of the tracer into the contralateral inferior
      colliculus few anterogradely labelled boutons were seen on spherical and
      multipolar cells of type II in the anteroventral cochlear nucleus. Rare labelled
      boutons were present on multipolar cells of type I and II, globular neurons and
      octopus cells in the posteroventral cochlear nucleus. After injection into the
      contralateral dorsal and ventral cochlear nucleus labelled boutons were seen more
      frequently than after injection into the inferior colliculus. These terminals
      contacted most of large neurons, especially multipolar cells of type II and less
      frequently of type I. Also globular and spherical cells were contacted by
      commissural terminals. Octopus cells received less frequently putative
      commissural terminals. Most boutons contained pleomorphic vesicles and stored
      GABA. A lower number of boutons with pleomorphic and flat vesicles contained
      glycine and sometimes GABA, both inhibitory neurotransmitters. Few boutons
      containing round vesicles were immuno-negative for both glycine and GABA, and
      were considered putative commissural excitatory terminals. The latter often
      contacted glycinergic neurons of type II so that also these terminals might
      elicit an inhibition with at least a disynaptic mechanism after contralateral
      stimulation.

PMID- 11297375
TI  - Unusual crystalline structures in photoreceptors of Lonchoplanella axi
      (Plathelminthes, Rhabdocoela, 'Typhloplanoida'): functional aspects and
      phylogenetic implications.
AB  - Lonchoplanella axi has a pair of small dot-like pigment-cup ocelli. Each eye is
      composed of a single cup cell and two sensory cells of the rhabdomeric type. The
      most conspicuous differentiations in the sensory cells are spindle-shaped
      crystalline structures accompanying the nuclei. These structures flank the
      dorsolateral, respectively ventrolateral side of the nucleus. It is supposed that
      these 'spindles' serve rather as an additional shading device than as dioptrics.
      Since such structures in photoreceptors have hitherto not been reported for
      representatives of the Plathelminthes, it is concluded that the spindle-shaped
      crystalline bodies in the eyes of Lonchoplanella axi are an autapomorphic feature
      of this species or even an autapomorphy of the taxon Mariplanellinae.

PMID- 11297376
TI  - Ultrastructural studies on the effect of heat shock treatment on larval salivary
      gland cells of Drosophila auraria.
AB  - In this study, the effect of heat shock treatment on Drosophila auraria late 3rd
      instar larval salivary glands was examined. Heat shock treatment was applied on
      whole animals and on isolated salivary glands. The fine structural changes were
      examined using transmission electron microscopy, after a temperature rise from
      normal (25 +/- 1degreesC) to 37 degreesC or 40 degreesC for various periods of
      time. The AcPace histochemical technique was used to demonstrate the acid
      phosphatase activity on lysosomal structures and x-ray microanalysis to determine
      the elemental composition of intramitochondrial granules. Our results indicate
      that the extent of heat shock damage on salivary gland cells depends on the heat
      shock intensity (temperature and duration). Three main changes were observed
      after heat shock treatment: a) appearance of lysosomal structures; b) alteration
      in the mitochondrial morphology and appearance of intramitochondrial granules and
      c) morphological alterations of secretory granules. Vesiculation of the Golgi
      complex and dilation of the rough endoplasmic reticulum were often seen.
      Irregular structures of unknown function were observed in the cytoplasm, which
      are referred to as x-structures. Rectangular secretory granules were observed in
      some cases, for the first time in a Drosophila species. These results are
      discussed in correlation with the heat shock effect on larval salivary glands of
      Drosophila.

PMID- 11297377
TI  - Ultrastructural localization of calcium deposits in rat myocardium after loud
      noise exposure.
AB  - In previous studies we demonstrated that loud noise exposure induces
      ultrastructural alterations in the rat myocardium together with an increase in
      noradrenergic activity and in mitochondrial calcium influx. To verify the causal
      relationship between myocardial calcium entry and ultrastructural alterations
      induced by loud noise, in the present study we coupled routine electron
      microscopy with cytochemistry specifically dedicated to visualize calcium
      accumulation (revealed as antimonate deposits). We observed that the
      ultrastructural alterations occurring in both atrium and ventricle after 12 h of
      noise exposure, were densely packed with antimonate deposits. In particular,
      enlargements of the sarcoplasmic reticulum and dilution of the mitochondrial
      matrix, observed during routine electron microscopy, were markedly positive for
      calcium accumulation when observed by using antimonate. The present data strongly
      suggest that calcium entry results in accumulation of this ion at myocardial
      subcellular level. Moreover, the present results joined with previous evidence
      indicate that calcium accumulation is the final common pathway responsible for
      noise-induced myocardial morphological alterations.

PMID- 11297378
TI  - Ultrastructure of the mature pollen of Michelia figo (Lour.) Spreng.
      (Magnoliaceae).
AB  - The structural organization of the Michelia figo mature pollen was investigated.
      The pollen wall consisted of an outer exine and an inner intine, the former being
      coated by a thin polysaccharide pellicle. The intine comprised three structurally
      distinct layers that were equally thick throughout the pollen surface. The
      generative cell (GC) was closely associated with the vegetative cell (VC) nucleus
      and its periplasm was found to maintain communication with the sporoderm through
      a complex plasmalemmic cord. In the freeze-fixed pollen a fluffy coat was
      detected on the cytoplasmic face of the VC plasmalemma bordering the GC. The
      plastids were present in only the VC and usually contained abundant small starch
      grains. In a few pollen grains, however, little or no starch existed and in this
      case one or more electron dense inclusions appeared in the plastids. Microbodies
      were found in both the VC and GC. In the VC they presumably have a glyoxysomal
      function as indicated by the numerous lipid droplets in the cytoplasm and the
      spatial relationship of microbodies with lipid droplets and/or mitochondria. In
      the GC the function of the microbodies is unclear once this cell had no abundant
      lipid reserves and the microbodies did not show any preferential relationship
      with other organelles. The most conspicuous feature of the VC cytoplasm was the
      high amount of storage vacuoles which displayed a striking different appearance
      after one and the other of the fixation techniques used. In contrast to the
      chemically fixed pollen they were quite polymorphic in the freeze-fixed pollen,
      and appeared uniformly filled with fibrillar material. Enzymatic digestion with
      protease has revealed most of this material to be proteinaceous in nature. The
      existence of phytin reserves is, however, also probable. These protein storage
      vacuoles closely resemble those in storage tissues of seeds and fruits.

PMID- 11297379
TI  - The effect of cyclophosphamide on brainstem remyelination following local
      ethidium bromide injection in Wistar rats.
AB  - Long-term cyclophosphamide (CY) treatment was used in male Wistar rats submitted
      to ethidium bromide (EB) demyelinating model to investigate ultrastructurally the
      drug effects on remyelination and on central nervous system (CNS) tissue repair.
      Demyelination was induced by a single 10 microl intracisternal injection of 0.1%
      EB solution and the rats anaesthetized and perfused through the heart from the
      15th to the 31st day after injection. Brainstem sections were collected and
      processed for light and transmission electron microscopy studies. At different
      times after EB injection, it was observed the presence of macrophages in
      phagocytic activity and non-degraded myelin debris in the extracellular space, as
      well as remyelinated and demyelinated axons. Remyelination was carried out by
      both oligodendrocytes and Schwann cells, the latter notably around blood vessels
      and in areas of expanded extracellular space. It was also noted groups of
      infiltrating meningeal cells and astrocytes showing hypertrophic processes with
      numerous bundles of glial filaments. The rats treated with CY showed greater
      amounts of myelin-derived membranes than non-treated rats, suggesting a delay in
      the macrophage activity of removing myelin debris. Additionally oligodendrocyte
      remyelinating activity showed an incipient and restricted pattern, with clear
      predominance of naked axons. Rare lymphocytes were also found, as well as
      decreased neovascularization.

PMID- 11297380
TI  - Cardiac ultrastructural alterations in mice inoculated with Tityus discrepans
      (Buthidae) venom.
AB  - In this work we have studied the cardiologic clinical manifestations appearing in
      response to toxic aggression by Tityus discrepans venom, such as hypertension,
      hypotension, tachycardia and pulmonary acute oedema. These depend on changes in
      the organisation of cellular and subcellular components of cardiac tissues and
      probably correspond with the damage found in envenomed humans. To evaluate
      cardiac tissue subcellular response to Tityus discrepans venom, male C57/B1 adult
      mice were randomised into two groups: envenomed mice were intraperitoneally
      injected at a dose of 5 mg/Kg of body weight and controls received saline
      solution. Samples from cardiac tissue were prepared for electron microscopy study
      and observed in a Hitachi-300. The most relevant cardiac ultrastructural findings
      in this model showed diffuse disarray of the myofibrils and abnormal pattern of
      the bands in the sarcomera, contractile element disorganisation, degeneration of
      fibres and loss of the characteristic sarcomeric structure given the appearance
      of a lax tissue. One of the most prominent features was the presence of a
      remarkable perinuclear oedema and the perinuclear cistern exhibited indentations
      over its whole arrangement. The vascular endothelium of the microvessels
      exhibited alterations with evident cytoplasmic projections toward the lumen of
      the vessel. Mitochondria presented a condensed conformation. All findings were
      degenerative signs of the contractile apparatus. We suggest that any cardiac
      tissue damage produced by toxins present in this venom are responsible for some
      of the clinical manifestations in envenomed animals and patients.

PMID- 11297381
TI  - Spermatogenesis in the grasscutter, Thryonomis swinderianus (Rodentia).
AB  - Spermatogenesis in the grasscutter, Thryonomis swinderianus, is characterized by
      remarkable diversification of the endoplasmic reticulum. In spermatocytes,
      besides the usual form with flat cisternae and vesicles, this membrane system
      forms unusually wide cisternae and vacuoles containing moderately electron dense
      material near the Golgi apparatus and the cell membrane. In spermatids a whorl of
      smooth cisternae enclosing aggregates of granular electron dense material appears
      as another specialization. Although all parts of the endoplasmic reticulum are in
      connection with each other, their distinct structural differences suggest
      functionally different subcompartments. Once established, the structures persist
      even after cytoplasm has been discarded from the nearly mature sperm. In the
      elongating spermatid a thin plica of the Sertoli cell begins to separate the
      developing structures from the remainder of the cytoplasm containing the
      endomembrane systems, part of which is further ensheathed when this fold enroles
      to form an incomplete tube. Occasionally, in late spermatids a spindle-shaped
      body of paracrystalline structure occurs temporarily around the flagellum at the
      beginning of the main piece.

PMID- 11297382
TI  - Ultrastructure of Sorubim lima (Teleostei, Siluriformes, Pimelodidae)
      spermiogenesis.
AB  - The spermiogenesis and the spermatozoon ultrastructure of Sorubim lima were
      studied. Our observations showed that early spermatids are round-shaped cells,
      have spherical nucleus with diffuse chromatin, small quantity of mitochondria and
      large amount of vesicles in the cytoplasm. During the differentiation process in
      the nucleus, chromatin compacts in a progressive and homogeneous way, and the
      flagellum is formed. In the cytoplasm the vesicles, that have double membranes,
      aggregate and fuse on the plasma membrane. The spermatozoa of S. lima have no
      acrosome and show spherical nucleus with homogeneous and highly compacted
      chromatin, intermediary piece with mitochondria and double wall vesicles
      contiguous to the plasma membrane, as well as a flagellum formed by a basic
      axoneme (9 + 2).

PMID- 11297383
TI  - Immunolocalization of different tubulin epitopes in the spermatozoon of Bacillus
      rossius (Insecta, Phasmatodea).
AB  - The existence of distinct tubulins in microtubules forming the sperm axoneme has
      been demonstrated in various species, whereas little is known about the
      distribution of tubulin variants in insect spermatozoa. In the present study, a
      panel of specific antibodies has been used to investigate the presence and
      localization of tubulin isotypes and post-translationally modified tubulins in
      the spermatozoon of the stick insect Bacillus rossius. Indirect
      immunofluorescence and immunogold staining showed differences in labelling in the
      mature sperm and that the tubulin epitopes localized differentially in the
      axoneme. In particular, the tyrosinated alpha-tubulin mainly occurs on doublets.
      These results provide an insight into the molecular composition of the
      microtubules forming the sperm axoneme of B. rossius and suggest that the
      structural specificity could reflect distinct functional roles within axonemal
      microtubules.

PMID- 11297384
TI  - The spermatozoon morphology of Solea senegalensis (Kaup, 1858) (Teleostei,
      Pleuronectiformes).
AB  - The spermatozoon of Solea senegalensis (Kaup, 1858) consists of an acrosome-less
      ovoid head, a short midpiece containing several irregular mitochondria embedded
      in the cytoplamic mass, and a long tail with two lateral fins and a conventional
      9 + 2 axoneme. The centrioles are housed in a deep nuclear fossa and are both
      orientated in the same longitudinal axis of the spermatozoon. The overall
      structure of this spermatozoon conforms to the sperm type considered to be
      plesiomorphic in the neopterigians (type I sperm). The likely apomorphic
      (coaxial) orientation of the centrioles defines the spermatozoal morphology of
      the Soleidae investigated thus far and separates them from the other known
      pleuronectiform spermatozoa.

PMID- 11297385
TI  - Endocytic activity in the thrombocytes of the turtle Phrynopys hilarii
      (freshwater South American species).
AB  - The phagocytic process in cells depends on lysosomal enzymes, high-energy
      metabolism and cellular recognition. In this paper, we investigated the presence
      of energy and recognition factors in thrombocytes of turtle Phrynopys hilarii (a
      freshwater South American species). Turtle thrombocytes (P. hilarii) present
      glycogen - possibly beta particles - dispersed in their cytoplasm and
      glycoproteins in the cell surface, as well as a large number of enzymes involved
      in the endocytic process (Pellizzon, 1996). The activity of these enzymes depends
      on high-energy metabolism and on cellular recognition provided by specific
      glycoconjugates (Alberts et al., 1994). This metabolic characterization is
      demonstrated by the large amount of glycogen particles observed in the cytoplasm
      by Thiery's method. Glycogen labeling was also observed when concanavalin A
      peroxidase was used as a marker for thrombocytes and for endocyted charcoal
      particles. Our results show that these cells have phagocytic ability, suggesting
      that their function in blood circulation is not limited to aggregation but may
      also involve a great potential for phagocytosis.

PMID- 11297386
TI  - The ultrastructure of pearl organs in Rutilus rubilio as revealed by scanning
      electron microscopy.
AB  - Pearl organs are epidermal structures that in the mating season appear on
      different body regions of fishes belonging to Catastomidae and Ciprynidae
      families. In veterinary medicine, pearl organs were studied for their possible
      role as index of fish good quality for human feeding. Recently some authors put
      in evidence the possible relationship with other secondary sexual characters to
      establish the stage of sexual maturation in fishes. Little is known about their
      morphology and morphogenesis. For these reasons, pearl organs of 10 specimens of
      Rutilus rubilio, collected in Caserta (Italy), were studied by light and scanning
      electron microscopy (SEM). By means of SEM, the presence of pearl organs was
      demonstrated on dorsal and lateral fins too and their fine structure was studied.
      This study permitted to show pearl organs at different evolutive stages
      clarifying their morphogenesis and suggesting some inspective and functional
      considerations.

PMID- 11297387
TI  - One- and two-stage upflow anaerobic sludge-bed reactor pretreatment of winery
      wastewater at 4-10 degreesC.
AB  - The operating performance of a single and two (in series) laboratory upflow
      anaerobic sludge-bed (UASB) reactors (2.7-L working volume, recycle ratio varied
      from 1:1 to 1:18) treating diluted wine vinasse was investigated under
      psychrophilic conditions (4-10 degreesC). For a single UASB reactor seeded with
      granular sludge, the average organic loading rates (OLRs) applied were 4.7, 3.7,
      and 1.7 g of chemical oxygen demand (COD)/(L.d) (hydraulic retention times [HRTs]
      were about 1 d) at 9-11, 6 to 7, and 4 to 5 degreesC, respectively. The average
      total COD removal for preacidified vinasse wastewater was about 60% for all the
      temperature regimes tested. For two UASB reactors in series, the average total
      COD removal for treatment of non-preacidified wastewater exceeded 70% (the
      average OLRs for a whole system were 2.2, 1.8, and 1.3 g of COD/[L.d] under HRTs
      of 2 d at 10, 7, and 4 degreesC, respectively). In situ determinations of kinetic
      sludge characteristics (apparent Vm and Km) revealed the existence of substantial
      mass transfer limitations for the soluble substrates inside the reactor sludge
      bed. Therefore, application of higher recycle ratios is essential for enhancement
      of UASB pretreatment under psychrophilic conditions. The produced anaerobic
      effluents were shown to be efficiently posttreated aerobically: final effluent
      COD concentrations were about 0.1 g/L. Successful operation of the UASB reactors
      at quite low temperatures (4-10 degreesC) opens some perspectives for application
      of high-rate anaerobic pretreatment at ambient temperatures.

PMID- 11297388
TI  - Affinity purification of secreted alkaline phosphatase produced by baculovirus
      expression vector system.
AB  - Human secreted alkaline phosphatase (SEAP) was produced in a stably-transformed
      Spodoptera frugiperda Sf-9 insect cell line (Sfb4GalT) following infection with a
      recombinant Autographa californica multiple nuclear polyhedrovirus containing the
      SEAP gene under control of the polyhedrin promoter. An affinity chromatographic
      column prepared by linking 4-amino-benzylphosphonic acid to histidyl-expoxy
      Sepharose was used to isolate SEAP from the cell supernatant following removal of
      cells and virus and 10-fold concentration through ultrafiltration. We found that
      the binding of SEAP on the affinity matrix follows the Langmuir isotherm model.
      In addition, either recycling SEAP sample through the column for 24 h or loading
      high SEAP concentrations resulted in a high-purity product. Some nonspecific
      binding of protein on the matrix occurred when low concentrations of SEAP sample
      were loaded. Finally, we found that SEAP binding occurs rapidly, i.e., within 30
      min of adding the SEAP sample to the affinity matrix.

PMID- 11297390
TI  - Thermozymes and their applications: a review of recent literature and patents.
AB  - Enzymes from thermophilic microorganisms, thermozymes, have unique
      characteristics such as temperature, chemical, and pH stability. They can be used
      in several industrial processes, in which they replace mesophilic enzymes or
      chemicals. Thermozymes are often used when the enzymatic process is compatible
      with existing (high-temperature) process conditions. The main advantages of
      performing processes at higher temperatures are reduced risk of microbial
      contamination, lower viscosity, improved transfer rates, and improved solubility
      of substrates. However, cofactors, substrates, or products might be unstable or
      other side reactions may occur. Recent developments show that thermophiles are a
      good source of novel catalysts that are of great industrial interest.
      Thermostable polymer-degrading enzymes such as amylases, pullulanases, xylanases,
      proteases, and cellulases are expected to play an important role in food,
      chemical, pharmaceutical, paper, pulp, and waste-treatment industries.
      Considerable research efforts have been made to better understand the stability
      of thermozymes. There are no major conformational differences with mesophilic
      enzymes, and a small number of extra salt bridges, hydrophobic interactions, or
      hydrogen bounds seem to confer the extra degree of stabilization. Currently,
      overexpression of thermozymes in standard Escherichia coli allows the production
      of much larger quantities of enzymes, which are easy to purify by heat treatment.
      With wider availability and lower cost, thermophilic enzymes will see more
      application in industry.

PMID- 11297389
TI  - Studies on digestive proteases from midgut glands of a shrimp, Penaeus indicus,
      and a lobster, Nephrops norvegicus: Part 1. Proteolytic activity.
AB  - Digestive gland protease pH optima and specific activities determined in Penaeus
      indicus with casein, azocasein, Azocoll, and Congo red fibrin as substrates were
      pH 7.7-9.2, 210-371 micromol of tyrosine/mg of homogenate protein/min; pH 7.8,
      36; pH 6.0-7.0, 7; and pH 8.9-9.2, 7A delta0.001 U/mg of homogenate protein/min,
      respectively. Activity in the shrimp was stable during frozen storage but
      relatively labile and very low (1.043 azocasein units) in the Norwegian lobster,
      Nephrops norvegicus. The high activity in shrimp is significant in aquaculture
      and may be a source of proteolytic enzymes for industrial use. The rapid
      deterioration after landing may be a consequence of the high and stable activity.
      The low activity in the lobster may present a problem in culture and requires a
      more critical choice of feed as well as further investigation. 4-(2-Aminoethyl)
      benzenesulfonyl fluoride hydrochloride was a very convenient, fast-acting, and
      effective inhibitor of shrimp trypsin and chymotrypsin but did not completely
      inhibit general protease activity in shrimp and had a negligible effect on the
      lobster. A significant component of that activity may be from nonserine proteases
      (such as the exoproteases carboxypeptidase A and B and the leucine
      aminopeptidases), whose proportion relative to the serine proteases may be
      greater in the lobster.

PMID- 11297391
TI  - Cytochrome-c detection: a diagnostic marker for myocardial infarction.
AB  - Following a myocardial infarction (MI) cells die or are damaged and their
      contents leak into the blood circulation, resulting in elevated serum levels of
      various enzymes, proteins, and organic molecules. Over the past few decades, it
      has become standard practice to employ the detection of these elevated substances
      as markers for the confirmation of MIs and to monitor MI patients' response to
      treatment. Although it has previously been shown that cytochrome-c, a small
      respiratory protein, is among those elevated, the lack of a suitable detection
      system has prevented its routine use in the diagnosis of MIs. We present a
      preliminary study in which chemiluminescence was employed to detect elevated
      levels of cytochrome-c in the serum of MI patients. The technique, which is
      specific for c-type proteins, is approx 30 times more sensitive than the
      traditional Coomassie blue stain and can detect as little as 0.03 microg of
      protein. It also has potential for diagnostic use in other diseases that are
      characterized by mitochondrial damage.

PMID- 11297392
TI  - Distribution of organochlorine pesticides in soils from South Korea.
AB  - Soil samples were collected from rice growing and industrial areas in South Korea
      and analysed for organochlorine pesticide content using gas chromatography with
      electron capture detection. The soils were monitored for the presence of 18
      organochlorine pesticides. The main pesticides found were gamma- and delta
      hexachlorocyclohexane, heptachlor epoxide and dieldrin. The range of
      concentrations, for each compound, was respectively, 0.17-0.94, 0.77-2.97, 1.38
      48.0 and 0.32-0.49 ng/g soil. The highest values were found in soil obtained from
      rice fields indicating that, although the use of organochlorine pesticides has
      been discontinued since 1980, substantial concentrations of residues particularly
      the oxidised form of heptachlor remain in the soil.

PMID- 11297393
TI  - Photocatalytic degradation of pentachlorophenol on TiO2 sol-gel catalysts.
AB  - The photocatalytic degradation of pentachlorophenol (PCP) in aqueous solution was
      investigated using TiO2 catalysts. The samples were prepared by the sol-gel
      method using different gelation pH and different calcination temperatures. The
      solids were characterized by specific surface area, X-ray diffraction, UV-Vis
      absorbance, FTIR and pentachlorophenol adsorption. The catalytic activity of the
      solids was evaluated in a conventional photoreactor at 298 K using 30 ppm of
      pentachlorophenol. It was found that the reaction follows a first-order reaction
      and the kinetic constant values change slightly with the pH of gelation and more
      significantly with the calcination temperature.

PMID- 11297394
TI  - Organochlorine formation in magnesium electrowinning cells.
AB  - The formation of organochlorines during the electrolytic production of magnesium
      was investigated using a laboratory-scale electrolytic cell having a graphite
      anode, a liquid aluminium alloy cathode, and a molten chloride electrolyte. The
      cell was operated at current densities ranging from 3000 to 10,000 A m(-2) and at
      temperatures ranging from 660 degrees C to 750 degrees C. Organochlorines were
      adsorbed from the cell off-gases onto silica gel, extracted with hexane, and
      determined by gas chromatography. All compounds identified were fully chlorinated
      aliphatic and aromatic compounds, the major components being hexachlorobutadiene,
      hexachlorobenzene, hexachloroethylene, and octachlorostyrene. The total amount of
      organochlorines per tonne of magnesium produced decreased with electrolysis time
      and with current density and increased with operating temperature; it was also
      dependent on the type of graphite employed. The output of organochlorines varied
      from 5 to 20 g t(-1) of magnesium.

PMID- 11297395
TI  - Toxicity of mono-, di- and tri-chlorophenols to lux marked terrestrial bacteria,
      Burkholderia species Rasc c2 and Pseudomonas fluorescens.
AB  - Burkholderia species RASC and Pseudomonas fluorescens were marked with lux genes,
      encoding for bioluminescence and used to assess the toxicity of mono-, di- and
      tri-chlorophenols by determining the decline in bioluminescence following
      exposure to the compounds in aqueous solution. Toxicity was expressed as a 50%
      effective concentration value (EC50, equating to the concentration of compound
      which caused a 50% decline in bioluminescence. Comparing the toxicity values of
      the compounds showed that, in general, increasing the degree of chlorination,
      increased toxicity. By carrying out forward multiple linear regressions with
      log10 EC50 values and physio-chemical descriptors, it was shown that molecular
      parameters describing the hydrogen bonding nature of a chlorophenol provided a
      better fit than regressions between toxicity data and log10 Kow alone. Utilising
      these descriptor variables in equations, it was shown that the toxicity of
      chlorophenols to the lux marked bacteria could be predicted from the compounds
      physio-chemical characteristics. By correlating lux marked RASC c2 and P.
      fluorescens EC50 values with toxicity values using Pimephales promelas (fathead
      minnow), Tetrahymena pyriformis (ciliate) and marine bacterium Vibriofischeri, it
      was apparent that lux marked RASC c2 correlated well with the freshwater aquatic
      species (P. promelas and T. pyriformis). This implied that for predictions of
      toxicity of organic xenobiotic compounds to higher organisms, lux marked RASC c2
      could be utilised as a rapid surrogate.

PMID- 11297396
TI  - Global hexachlorobenzene emissions.
AB  - Information from a variety of sources has been assembled to give a global picture
      of hexachlorobenzene (HCB) emissions in the mid 1990s. No single overwhelming
      source of HCB was identified. The best estimates of global HCB emissions from
      different categories of sources are as follows: pesticides application - 6500
      kg/yr; manufacturing - 9500 kg/yr; combustion - 7000 kg/yr, includes 500 kg from
      biomass burning. This adds up to total current HCB emissions of approximately
      23,000 kg/yr with an estimated range 12,000-92,000 kg/yr. A substantial portion
      of HCB measured in the atmosphere is thought to come from volatilization of "old"
      HCB on the soil from past contamination along with unidentified sources. No
      information on potential sources in developing countries was available.

PMID- 11297397
TI  - A congener-specific PCDD/F emissions inventory for the UK: do current estimates
      account for the measured atmospheric burden?
AB  - Considerable effort has been expended in the UK and elsewhere to quantify and
      rank PCDD/F primary sources and emissions to the environment, principally the
      atmosphere, so that cost-effective source reduction measures can be taken. Here,
      we predict a congener-specific emissions inventory for primary and secondary
      nondioxin-regulated sources to the UK atmosphere, estimated to have ranged from 3
      to 22 kg in 1996. The inventory profile is dominated by OCDD (approximately 30
      40%), 1,2,3,4,6,7,8-HpCDD (approximately 15-19%) and 1,2,3,4,6,7,8-HpCDF
      (approximately 14-19%). Congeners 2,3,4,7,8-PeCDF and 1,2,3,7,8-PeCDD dominate
      the sigmaTEQ composition. Mass balance modelling suggests that the predicted
      congener pattern in UK air (based on the emission inventory) is similar to
      observed measurements, with absolute concentrations being estimated within a
      factor of 2 for most congeners. Calculations taking into account atmospheric
      weathering processes and long range (advective) transport suggest that PCDD/F
      sources to ambient air are primarily ongoing and that atmospheric mixing will
      mask individual emission source profiles/identities. This supports measured
      evidence for the consistency of PCDD/F air profiles observed around the UK
      throughout the year.

PMID- 11297398
TI  - The complete dechlorination of DDT by magnesium/palladium bimetallic particles.
AB  - The complete dechlorination of 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane
      (DDT) by a magnesium/palladium bimetallic system has been accomplished. The
      reaction takes place under ambient temperature and pressure and mild reaction
      conditions requiring only 0.25 g of magnesium and 0.3% palladium (wt/wt) to drive
      the dechlorination of 100 microg DDT (50 ppm in 2 ml). The process is both rapid
      and complete requiring less than 10 min to attain total dechlorination within the
      detection limit (approximately 10 pg for DDT) of electron capture detection gas
      chromatography (GC-ECD). The major product formed, as deduced from mass
      spectrometry (GC-MS) is the hydrocarbon skeleton, 1,1-diphenylethane. This
      technology may allow for the development of an economic and environmentally
      benign method of DDT remediation.

PMID- 11297399
TI  - PCDD/F reduction in incinerator flue gas by adding urea to RDF feedstock.
AB  - The effect of urea on PCDD/F formation in a pilot incinerator was studied by
      incinerating urea with refuse-derived fuel (RDF) at three concentrations (0.1%,
      0.5% and 1.0%, of the fuel feed). A distinct reduction in both PCDD/F and
      chlorophenol concentrations could be noticed when urea was introduced into the
      system. Partial-least-square (PLS) analysis of the data showed the importance of
      certain chlorophenol isomers as PCDD/F precursors, pointing to the possibility
      that the impact point of the urea inhibitor could be before the precursor
      molecules, i.e. chlorophenols, have been formed.

PMID- 11297400
TI  - PCB congener selective biodegradation by the white rot fungus Pleurotus ostreatus
      in contaminated soil.
AB  - Six strains of white rot fungi were tested for their biodegradation ability of
      low chlorinated polychlorinated biphenyl (PCB) commercial mixture (Delor 103) in
      real soil system. Phanerochaete chrysosporium and Trametes versicolor did not
      show any ability to degrade PCBs in soil. On the contrary, four strains of
      Pleurotus ostreatus were able to remove about 40% of Delor 103 in two months. All
      P. ostreatus strains decomposed PCBs selectively with the preference for
      congeners with chlorine atoms in ortho > meta > para position. Degradation
      efficiency decreased with increasing number of chlorination.

PMID- 11297401
TI  - PCDD/F concentrations in soil and vegetation in the vicinity of a municipal waste
      incinerator after a pronounced decrease in the emissions of PCDD/Fs from the
      facility.
AB  - Emission of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)
      by municipal solid waste incinerators (MSWI) is an issue of great concern. In
      1997, an adaptation to the EU legislation on pollutant emissions from the stack
      was carried out in an MSWI from Tarragona (Catalonia, Spain). As a result, PCDD/F
      emissions were significantly reduced. The aim of this study was to determine the
      current levels of PCDD/Fs in soil and vegetation samples collected near the
      facility and to compare these levels with those obtained in previous surveys
      (1996 and 1997). In the period 1997-1999, PCDD/F concentrations in vegetation
      samples were significantly decreased (60%). By contrast, the levels of PCDD/Fs in
      soil samples increased slightly (14%, P > 0.05) during the same period. An
      exhaustive analysis of the present data indicates that other emission sources of
      PCDD/Fs have also a notable environmental impact on the area under direct
      influence of the MSWI.

PMID- 11297402
TI  - The influence of level and chlorine source on the formation of mono- to octa
      chlorinated dibenzo-p-dioxins, dibenzofurans and coplanar polychlorinated
      biphenyls during combustion of an artificial municipal waste.
AB  - The formation of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs) and the three coplanar polychlorinated biphenyls (pPCBs)
      was studied during labscale fludized bed combustion of eight artificial municipal
      solid waste (MSW) fuel mixtures. The level of chlorine as well as the chlorine
      source varies within the different fuel mixtures. Four different chlorine sources
      were studied, viz, an inorgnaic (NaCl) and three organic sources, pure PVC
      plastic and two products (floor and cable) and the total chlorine level varies
      between 0.28% and 1.1%. The experiments were performed in a 5 kW laboratory scale
      fluidized bed reactor. A correlation between the total chlorine in the fuel and
      the formation of the hepta- and octa-chlorinated PCDD/F homologues was found.
      However, the most important variable for changes in the PCDDs/Fs and pPCBs
      formation was disturbance in the combustion condition and not the variation in
      chlorine content of the fuel. Furthermore, no differences in formation between
      the chlorine sources could be seen.

PMID- 11297403
TI  - Quantitative structure-property relationships (QSPRs) on direct photolysis
      quantum yields of PCDDs.
AB  - By the use of partial least squares (PLS) method and 16 fundamental quantum
      chemical descriptors computed by PM3 Hamiltonian, quantitative structure-property
      relationships (QSPRs) were obtained for direct photolysis quantum yields of
      selected polychlorinated dibenzo-p-dioxins (PCDDs). Direct photolysis quantum
      yields for PCDDs without experimental quantum yield values were predicted. The
      QSPR results showed that it was mainly the number of chlorine atoms bonded to the
      parent structure, the largest positive atomic charge on a chlorine atom, the
      dipole moment, and the frontier molecular orbital energies (Ehomo and Elumo) that
      determine the direct photolysis quantum yields of the PCDDs. Increasing the
      number of chlorine atoms, dipole moment, and the largest positive atomic charge
      on a chlorine atom, leads to decrease of photolysis quantum yields. Increasing
      Elumo, Ehomo and Elumo - Ehomo values lead to increase of log Y values.

PMID- 11297404
TI  - Factors affecting the transfer of organochlorine pesticide residues to
      breastmilk.
AB  - Existing studies monitoring organochlorine pesticide residues in breastmilk were
      examined to identify whether common factors determine the extent of transfer of
      these residues. A structured review of the English language literature was
      conducted. Papers were reviewed and assessed using a structured protocol. A total
      of 77 papers were initially identified, 46 of which contained conclusions
      relating to the factors which may affect the transfer of residues into
      breastmilk. Owing to the diversity of findings, papers were screened further to
      include only those in which a minimum of background information relating to
      selection of mothers and to milk sampling procedures were reported. Only eight
      papers were deemed to contain adequate information. Age, parity/length of
      previous lactation, fat mobilisation and the time of sampling were identified as
      the most likely factors to be considered when assessing transfer of
      organochlorine pesticide residues into breastmilk. This review highlights the
      difficulties of assessing trends in breastmilk contaminants where comparable
      sampling procedures are not used.

PMID- 11297405
TI  - Opportunities for a probabilistic risk assessment of chemicals in the European
      Union.
AB  - In risk assessment of new and existing substances, it is current practice to
      characterise risk using a deterministic quotient of the exposure concentration,
      or the dose, and a no-effect level. A sense of uncertainty is tackled by
      introducing worst-case assumptions in the methodology. Since this procedure leads
      to an assessment with an unknown degree of conservatism, it is advisable to deal
      quantitatively with uncertainties. This paper discusses the advantages and
      possibilities of a probabilistic risk assessment framework, illustrated with an
      example calculation. Furthermore, representatives of EU Member States and the
      chemical industry were interviewed to find out their views on applying
      uncertainty analysis to risk assessment of industrial chemicals.

PMID- 11297406
TI  - A novel view of pH titration in biomolecules.
AB  - When individual titratable sites in a molecule interact with each other, their pH
      titration can be considerably more complex than that of an independent site
      described by the classical Henderson-Hasselbalch equation. We propose a novel
      framework that decomposes any complex titration behavior into simple standard
      components. The approach maps the set of N interacting sites in the molecule onto
      a set of N independent, noninteracting quasi-sites, each characterized by a
      pK'(a) value. The titration curve of an individual site in the molecule is a
      weighted sum of Henderson-Hasselbalch curves corresponding to the quasi-sites.
      The total protonation curve is the unweighted sum of these Henderson-Hasselbalch
      curves. We show that pK'(a) values correspond to deprotonation constants
      available from methods that can be used to assess total proton uptake or release,
      and establish their connection to protonation curves of individual residues
      obtained by NMR or infrared spectroscopy. The new framework is tested on a small
      molecule diethylenetriaminepentaacetate (DTPA) exhibiting nonmonotonic titration
      curves, where it gives an excellent fit to experimental data. We demonstrate that
      the titration curve of a site in a group of interacting sites can be accurately
      reconstructed, if titration curves of the other sites are known. The application
      of the new framework to the protein rubredoxin demonstrates its usefulness in
      calculating and interpreting complicated titration curves.

PMID- 11297407
TI  - Phosphodiesterase A1, a regulator of cellulose synthesis in Acetobacter xylinum,
      is a heme-based sensor.
AB  - The phosphodiesterase A1 protein of Acetobacter xylinum, AxPDEA1, is a key
      regulator of bacterial cellulose synthesis. This phosphodiesterase linearizes
      cyclic bis(3'-->5')diguanylic acid, an allosteric activator of the bacterial
      cellulose synthase, to the ineffectual pGpG. Here we show that AxPDEA1 contains
      heme and is regulated by reversible binding of O(2) to the heme. Apo-AxPDEA1 has
      less than 2% of the phosphodiesterase activity of holo-AxPDEA1, and
      reconstitution with hemin restores full activity. O(2) regulation is due to
      deoxyheme being a better activator than oxyheme. AxPDEA1 is homologous to the
      Escherichia coli direct oxygen sensor protein, EcDos, over its entire length and
      is homologous to the FixL histidine kinases over only a heme-binding PAS domain.
      The properties of the heme-binding domain of AxPDEA1 are significantly different
      from those of other O(2)-responsive heme-based sensors. The rate of AxPDEA1
      autoxidation (half-life > 12 h) is the slowest observed so far for this type of
      heme protein fold. The O(2) affinity of AxPDEA1 (K(d) approximately 10 microM) is
      comparable to that of EcDos, but the rate constants for O(2) association (k(on) =
      6.6 microM(-)(1) s(-)(1)) and dissociation (k(off) = 77 s(-)(1)) are 2000 times
      higher. Our results illustrate the versatility of signal transduction mechanisms
      for the heme-PAS class of O(2) sensors and provide the first example of O(2)
      regulation of a second messenger.

PMID- 11297408
TI  - Polyproline II helix is a key structural motif of the elastic PEVK segment of
      titin.
AB  - Titin is a family of giant elastic proteins that constitute an elastic sarcomere
      matrix in striated muscle. In the I-band region of the sarcomere, where titin
      extends and develops passive force upon stretch, titin is composed of tandem
      repeats of approximately 100 residue immunoglobin domains and approximately 28
      residue PEVK modules. We have performed 2D NMR and circular dichroism (CD)
      studies of the conformations of one representative 28-mer PEVK module from human
      fetal titin (PEPPKEVVPEKKAPVAPPKKPEVPPVKV). NMR data of synthetic peptides of
      this module as well as three constituent peptides of 9 to 12 residues in aqueous
      solutions reveal distinguishing features for left-handed three-residue per turn
      PPII helices: the lack of NOE NN(i, i+1), very large NOE alphaN(i, i+1)/NN(i,
      i+1), no medium range NOE alphaN(i, i+2), and dihedral angles phi and psi values
      of -78 and 146, respectively. Structural determinations indicate the presence of
      three short stretches of PPII helices of 4, 5, and 6 residues that are interposed
      with an unordered, and presumably flexible, spacer region to give one
      "polyproline II helix-coil" or "PhC" motif for roughly every 10 residues. These
      peptides also display the characteristic PPII CD spectra: positive peak or
      negative shoulder band at 223 nm, negative CD band near 200 nm, and biphasic
      thermal titration curves that reflect varied stability of these PPII helices. We
      propose that this PhC motif is a fundamental feature and that the number, length,
      stability, and distribution of PPII is important in the understanding of the
      elasticity and protein interactions of the PEVK region of titin.

PMID- 11297409
TI  - Backbone dynamics of the calcium-signaling protein apo-S100B as determined by 15N
      NMR relaxation.
AB  - Backbone dynamics of homodimeric apo-S100B were studied by (15)N nuclear magnetic
      resonance relaxation at 9.4 and 14.1 T. Longitudinal relaxation (T(1)),
      transverse relaxation (T(2)), and the (15)N-[(1)H] NOE were measured for 80 of 91
      backbone amide groups. Internal motional parameters were determined from the
      relaxation data using the model-free formalism while accounting for diffusion
      anisotropy. Rotational diffusion of the symmetric homodimer has moderate but
      statistically significant prolate axial anisotropy (D( parallel)/D(
      perpendicular) = 1.15 +/- 0.02), a global correlation time of tau(m) = 7.80 +/-
      0.03 ns, and a unique axis in the plane normal to the molecular symmetry axis. Of
      29 residues at the dimer interface (helices 1 and 4), only one has measurable
      internal motion (Q71), and the order parameters of the remaining 28 were the
      highest in the protein (S(2) = 0.80 to 0.91). Order parameters in the typical EF
      hand calcium-binding loop (S(2) = 0.73 to 0.87) were slightly lower than in the
      pseudo-EF hand (S(2) = 0.75 to 0.89), and effective internal correlation times,
      tau(e), distinct from global tumbling, were detected in the calcium-binding
      loops. Helix 3, which undergoes a large, calcium-induced conformational change
      necessary for target-protein binding, does not show evidence of interchanging
      between the apo and Ca(2+)-bound orientations in the absence of calcium but has
      rapid motion in several residues throughout the helix (S(2) = 0.78 to 0.88; 10 <
      or = tau(e) < or = 30 ps). The lowest order parameters were found in the C
      terminal tail (S(2) = 0.62 to 0.83). Large values for chemical exchange also
      occur in this loop and in regions nearby in space to the highly mobile C-terminal
      loop, consistent with exchange broadening effects observed.

PMID- 11297410
TI  - Effect of the disulfide bridge and the C-terminal extension on the
      oligomerization of the amyloid peptide ABri implicated in familial British
      dementia.
AB  - Familial British dementia (FBD) is a rare neurodegenerative disorder and shares
      features with Alzheimer's disease, including amyloid plaque deposits,
      neurofibrillary tangles, neuronal loss, and progressive dementia.
      Immunohistochemical and biochemical analysis of plaques and vascular amyloid of
      FBD brains revealed that a 4 kDa peptide named ABri is the main component of the
      highly insoluble amyloid deposits. In FBD patients, the ABri peptide is produced
      as a result of a point mutation in the usual stop codon of the BRI gene. This
      mutation produces a BRI precursor protein 11 amino acids longer than the wild
      type protein. Mutant and wild-type precursor proteins both undergo furin cleavage
      between residues 243 and 244, producing a peptide of 34 amino acids in the case
      of ABri and 23 amino acids in the case of the wild-type (WT) peptide. Here we
      demonstrate that the intramolecular disulfide bond in ABri and the C-terminal
      extension are required to elongate initially formed dimers to oligomers and
      fibrils. In contrast, the shorter WT peptide did not aggregate under the same
      conditions. Conformational analyses indicate that the disulfide bond and the C
      terminal extension of ABri are required for the formation of beta-sheet
      structure. Soluble nonfibrillar ABri oligomers were observed prior to the
      appearance of mature fibrils. A molecular model of ABri containing three beta
      strands, and two beta-hairpins annealed by a disulfide bond, has been
      constructed, and predicts a hydrophobic surface which is instrumental in
      promoting oligomerization.

PMID- 11297411
TI  - Disulfide bond structure of the AVR9 elicitor of the fungal tomato pathogen
      Cladosporium fulvum: evidence for a cystine knot.
AB  - Disease resistance in plants is commonly activated by the product of an
      avirulence (Avr) gene of a pathogen after interaction with the product of a
      matching resistance (R) gene in the host. In susceptible plants, Avr products
      might function as virulence or pathogenicity factors. The AVR9 elicitor from the
      fungus Cladosporium fulvum induces defense responses in tomato plants carrying
      the Cf-9 resistance gene. This 28-residue beta-sheet AVR9 peptide contains three
      disulfide bridges, which were identified in this study as Cys2-Cys16, Cys6-Cys19,
      and Cys12-Cys26. For this purpose, AVR9 was partially reduced, and the thiol
      groups of newly formed cysteines were modified to prevent reactions with
      disulfides. After HPLC purification, the partially reduced peptides were
      sequenced to determine the positions of the modified cysteines, which originated
      from the reduced disulfide bridge(s). All steps involving molecules with free
      thiol groups were performed at low pH to suppress disulfide scrambling. For that
      reason, cysteine modification by N-ethylmaleimide was preferred over modification
      by iodoacetamide. Upon (partial) reduction of native AVR9, the Cys2-Cys16 bridge
      opened selectively. The resulting molecule was further reduced to two one-bridge
      intermediates, which were subsequently completely reduced. The (partially)
      reduced cysteine-modified AVR9 species showed little or no necrosis-inducing
      activity, demonstrating the importance of the disulfide bridges for biological
      activity. Based on peptide length and cysteine spacing, it was previously
      suggested that AVR9 isa cystine-knotted peptide. Now, we have proven that the
      bridging pattern of AVR9 is indeed identical to that of cystine-knotted peptides.
      Moreover, NMR data obtained for AVR9 show that it is structurally closely related
      to the cystine-knotted carboxypeptidase inhibitor. However, AVR9 does not show
      any carboxypeptidase inhibiting activity, indicating that the cystine-knot fold
      is a commonly occurring motif with varying biological functions.

PMID- 11297412
TI  - Internalization of the human N-formyl peptide and C5a chemoattractant receptors
      occurs via clathrin-independent mechanisms.
AB  - After stimulation by ligand, most G protein-coupled receptors (GPCRs) undergo
      rapid phosphorylation, followed by desensitization and internalization. In the
      case of the N-formyl peptide receptor (FPR), these latter two processing steps
      have been shown to be entirely dependent on phosphorylation of the receptor's
      carboxy terminus. We have previously demonstrated that FPR internalization can
      occur in the absence of receptor desensitization, indicating that FPR
      desensitization and internalization are regulated differentially. In this study,
      we have investigated whether human chemoattractant receptors internalize via
      clathrin-coated pits. Internalization of the FPR transiently expressed in HEK 293
      cells was shown to be dependent upon receptor phosphorylation. Despite this,
      internalization of the FPR, as well as the C5a receptor, was demonstrated to be
      independent of the actions of arrestin, dynamin, and clathrin. In addition, we
      utilized fluorescence microscopy to visualize the FPR and beta(2)-adrenergic
      receptor as they internalized in the same cell, revealing distinct sites of
      internalization. Last, we found that a nonphosphorylatable mutant of the FPR,
      unable to internalize, was competent to activate p44/42 MAP kinase. Together,
      these results demonstrate not only that the FPR internalizes via an arrestin-,
      dynamin-, and clathrin-independent pathway but also that signal transduction to
      MAP kinases occurs in an internalization-independent manner.

PMID- 11297413
TI  - Xenon and halogenated alkanes track putative substrate binding cavities in the
      soluble methane monooxygenase hydroxylase.
AB  - To investigate the role of protein cavities in facilitating movement of the
      substrates, methane and dioxygen, in the soluble methane monooxygenase
      hydroxylase (MMOH), we determined the X-ray structures of MMOH from Methylococcus
      capsulatus (Bath) cocrystallized with dibromomethane or iodoethane, or by using
      crystals pressurized with xenon gas. The halogenated alkanes bind in two cavities
      within the alpha-subunit that extend from one surface of the protein to the
      buried dinuclear iron active site. Two additional binding sites were located in
      the beta-subunit. Pressurization of two crystal forms of MMOH with xenon resulted
      in the identification of six binding sites located exclusively in the alpha
      subunit. These results indicate that hydrophobic species bind preferentially in
      preexisting cavities in MMOH and support the hypothesis that such cavities may
      play a functional role in sequestering and enhancing the availability of the
      physiological substrates for reaction at the active site.

PMID- 11297414
TI  - Carbonmonoxy horseradish peroxidase as a function of pH and substrate: influence
      of local electric fields on the optical and infrared spectra.
AB  - Infrared and optical spectra of carbonmonoxy horseradish peroxidase were
      monitored as a function of pH and substrate binding. The analyses of experimental
      results together with semiempirical calculations show that the CO-porphyrin
      complex is sensitive to environmental changes. The electronic Q(0,0) band of the
      porphyrin and the CO stretching mode respond to external perturbations with
      different symmetry dependencies. In this way, the complex is nonisotropic, and
      the combined spectral analyses constitute a valuable tool for the investigation
      of structure. In the absence of substrate and at pH 6.0, the low-spin heme
      optical Q(0,0) absorption band is a single peak that narrows as the temperature
      decreases. Under these conditions, the CO vibrational stretch frequency is at
      1903 cm(-1). Addition of the substrates benzohydroxamic acid or naphthohydroxamic
      acid produces a split of approximately 320 cm(-1) in the Q(0,0) absorption band
      that is clearly evident at < 100 K and shifts the CO absorption to 1916 cm(-1).
      Increasing the pH to 9.3 also causes a split in the Q(0,0) optical band and
      elicits a shift in nu(CO) to a higher frequency (1936 cm(-1)). The splitting of
      the Q(0,0) band and the shifts in the IR spectra are both consistent with changes
      in the local electric field produced by the proximity of the electronegative
      carbonyl of the substrate near the heme or the protonation and/or deprotonation
      of the distal histidine, although other effects are also considered. The larger
      effect on the Q(0,0) band with substrate at low pH and the shift of nu(CO) at
      high pH can be rationalized by the directionality of the field and the
      orientation dependence of dipolar interactions.

PMID- 11297415
TI  - Antitumor action of seminal ribonuclease, its dimeric structure, and its
      resistance to the cytosolic ribonuclease inhibitor.
AB  - Bovine seminal RNase (BS-RNase) is a homodimeric enzyme with a cytotoxic activity
      selective for tumor cells. In this study, the relationships of its cytotoxic
      activity to its dimeric structure and its resistance to the cytosolic RNase
      inhibitor (cRI) are investigated systematically by site-directed mutagenesis. The
      results show that (1) the dimericity of BS-RNase is essential for its full
      cytotoxic action; (2) the role of the dimeric structure in the antitumor activity
      is that of making the enzyme insensitive to the cytosolic RNase inhibitor; (3) a
      RNase may not be completely insensitive to cRI to exploit a full cytotoxic
      potential.

PMID- 11297416
TI  - Investigation of allosteric linkages in the regulation of tryptophan synthase:
      the roles of salt bridges and monovalent cations probed by site-directed
      mutation, optical spectroscopy, and kinetics.
AB  - The tryptophan synthase bienzyme complex is the most extensively documented
      example of substrate channeling in which the oligomeric unit has been described
      at near atomic resolution. Transfer of the common metabolite, indole, between the
      alpha- and the beta-sites occurs by diffusion along a 25-A-long interconnecting
      tunnel within each alphabeta-dimeric unit of the alpha(2)beta(2) oligomer. The
      control of metabolite transfer involves allosteric interactions that trigger the
      switching of alphabeta-dimeric units between open and closed conformations and
      between catalytic states of low and high activity. This allosteric signaling is
      triggered by covalent transformations at the beta-site and ligand binding to the
      alpha-site. The signals are transmitted between sites via a scaffolding of
      structural elements that includes a monovalent cation (MVC) binding site and salt
      bridging interactions of betaLys 167 with betaAsp 305 or alphaAsp 56. Through the
      combined strategies of site-directed mutations of these amino acid residues and
      cation substitutions at the MVC site, this work examines the interrelationship of
      the MVC site and the alternative salt bridges formed between Lys beta167 with Asp
      beta305 or Asp alpha56 to the regulation of channeling. These experiments show
      that both the binding of a MVC and the formation of the Lys beta167-Asp alpha56
      salt bridge are important to the transmission of allosteric signals between the
      sites, whereas, the salt bridge between betaK167 and betaD305 appears to be only
      of minor significance to catalysis and allosteric regulation. The mechanistic
      implications of these findings both for substrate channeling and for catalysis
      are discussed.

PMID- 11297418
TI  - Partially folded intermediates as critical precursors of light chain amyloid
      fibrils and amorphous aggregates.
AB  - Light chain, or AL, amyloidosis is a pathological condition arising from systemic
      extracellular deposition of monoclonal immunoglobulin light chain variable
      domains in the form of insoluble amyloid fibrils, especially in the kidneys.
      Substantial evidence suggests that amyloid fibril formation from native proteins
      occurs via a conformational change leading to a partially folded intermediate
      conformation, whose subsequent association is a key step in fibrillation. In the
      present investigation, we have examined the properties of a recombinant
      amyloidogenic light chain variable domain, SMA, to determine whether partially
      folded intermediates can be detected and correlated with aggregation. The results
      from spectroscopic and hydrodynamic measurements, including far- and near-UV
      circular dichroism, FTIR, NMR, and intrinsic tryptophan fluorescence and small
      angle X-ray scattering, reveal the build-up of two partially folded intermediate
      conformational states as the pH is decreased (low pH destabilized the protein and
      accelerated the kinetics of aggregation). A relatively nativelike intermediate,
      I(N), was observed between pH 4 and 6, with little loss of secondary structure,
      but with significant tertiary structure changes and enhanced ANS binding,
      indicating exposed hydrophobic surfaces. At pH below 3, we observed a relatively
      unfolded, but compact, intermediate, I(U), which was characterized by decreased
      tertiary and secondary structure. The I(U) intermediate readily forms amyloid
      fibrils, whereas I(N) preferentially leads to amorphous aggregates. Except at pH
      2, where negligible amorphous aggregate is formed, the amorphous aggregates
      formed significantly more rapidly than the fibrils. This is the first indication
      that different partially folded intermediates may be responsible for different
      aggregation pathways (amorphous and fibrillar). The data support the hypothesis
      that amyloid fibril formation involves the ordered self-assembly of partially
      folded species that are critical soluble precursors of fibrils.

PMID- 11297417
TI  - Solution structure of the toluene 4-monooxygenase effector protein (T4moD).
AB  - Toluene 4-monooxygenase (T4MO) from Pseudomonas mendocina catalyzes the NADH- and
      O(2)-dependent hydroxylation of toluene to form p-cresol. The complex consists of
      an NADH oxidoreductase (T4moF), a Rieske ferredoxin (T4moC), a diiron hydroxylase
      [T4moH, with (alphabetagamma)(2) quaternary structure], and a catalytic effector
      protein (T4moD). The solution structure of the 102-amino acid T4moD effector
      protein has been determined from 2D and 3D (1)H, (13)C, and (15)N NMR
      spectroscopic data. The structural model was refined through simulated annealing
      by molecular dynamics in torsion angle space (DYANA software) with input from
      1467 experimental constraints, comprising 1259 distance constraints obtained from
      NOEs, 128 dihedral angle constraints from J-couplings, and 80 hydrogen bond
      constraints. Of 60 conformers that met the acceptance criteria, the 20 that best
      satisfied the input constraints were selected to represent the solution
      structure. With exclusion of the ill-defined N- and C-terminal segments (Ser1
      Asn11 and Asp99-Met102), the atomic root-mean-square deviation for the 20
      conformers with respect to the mean coordinates was 0.71 A for the backbone and
      1.24 A for all non-hydrogen atoms. The secondary structure of T4moD consists of
      three alpha-helices and seven beta-strands arranged in an N-terminal
      betaalphabetabeta and a C-terminal betaalphaalphabetabetabeta domain topology.
      Although the published NMR structures of the methane monooxygenase effector
      proteins from Methylosinus trichosporium OB3b and Methylococcus capsulatus (Bath)
      have a similar secondary structure topology, their three-dimensional structures
      differ from that of T4moD. The major differences in the structures of the three
      effector proteins are in the relative orientations of the two beta-sheets and the
      interactions between the alpha-helices in the two domains. The structure of T4moD
      is closer to that of the methane monooxygenase effector protein from M.
      capsulatus (Bath) than that from M. trichosporium OB3b. The specificity of T4moD
      as an effector protein was investigated by replacing it in reconstituted T4MO
      complexes with effector proteins from monooxygenases from other bacterial
      species: Pseudomonas pickettii PKO1 (TbuV, toluene 3-monooxygenase); Pseudomonas
      species JS150 (TbmC, toluene 2-monooxygenase); and Burkeholderia cepacia G4 (S1,
      toluene 2-monooxygenase). The results showed that the closely related TbuV
      effector protein (55% sequence identity) provided partial activation of the
      complex, whereas the more distantly related TbmC (34% sequence identity) and S1
      (29% sequence identity) did not. The (1)H NMR chemical shifts of the side-chain
      amide protons of Asn34, a conserved, structurally relevant amino acid, were found
      to be similar in spectra of effector proteins T4moD and TbuV but not in the
      spectrum of TbmC. This suggests that the region around Asn34 may be involved in
      structural aspects contributing to functional specificity.

PMID- 11297419
TI  - The C-terminus of glutathione S-transferase A1-1 is required for entropically
      driven ligand binding.
AB  - Binding of a hydrophobic glutathione product conjugate to rGST A1-1 proceeds via
      a two-step mechanism, including rapid ligand docking, followed by a slow
      isomerization to the final [GST.ligand] complex, which involves the localization
      of the flexible C-terminal helix. These kinetically resolved steps have been
      observed previously by stopped-flow fluorescence with the wild-type rGST A1-1,
      which contains a native Trp-21 approximately 20 A from the ligand binding site at
      the intrasubunit domain-domain interface. To confirm this binding mechanism, as
      well as elucidate the effects of truncation of the C-terminus, we have further
      characterized the binding and dissociation of the glutathione-ethacrynic acid
      product conjugate (GS-EA) to wild-type, F222W:W21F, and Delta209-222 rGST A1-1
      and wild-type hGST A1-1. Although modest kinetic differences were observed
      between the hGST A1-1 and rGST A1-1, stopped-flow binding studies with GS-EA
      verified that the two-step mechanism of ligand binding is not unique to the GST
      A1-1 isoform from rat. An F222W:W21F rGST A1-1 double mutant provides a direct
      fluorescence probe of changes in the environment of the C-terminal residue. The
      observation of two relaxation times during ligand binding and dissociation to
      F222W:W21F suggests that the C-terminus has an intermediate conformation
      following ligand docking, which is distinct from its conformation in the
      apoenzyme or localized helical state. For the wild-type, Delta209-222, and
      F222W:W21F proteins, variable-temperature stopped-flow experiments were performed
      and activation parameters calculated for the individual steps of the binding
      reaction. Activation parameters for the binding reaction coordinate illustrate
      that the C-terminus provides a significant entropic contribution to ligand
      binding, which is completely realized within the initial docking step of the
      binding mechanism. In contrast, the slow isomerization step is enthalpically
      driven. The partitioning of entropic and enthalpic components of binding energy
      was confirmed by isothermal titration calorimetry with wild-type and Delta209-222
      rGST A1-1.

PMID- 11297420
TI  - Energetics of coiled coil folding: the nature of the transition states.
AB  - Coiled coils are simple models for studying the association of two polypeptide
      chains to form a folded protein. Previous work has shown that the folding of a
      coiled coil can be described by a two-state transition between two unfolded
      monomeric peptide chains and a folded coiled coil dimer. Here we report the
      thermodynamic activation parameters for the folding and unfolding of two
      unrelated coiled coils: C62GCN4 and A(2). C62GCN4 corresponds to the 62 C
      terminal residues of yeast transcription factor GCN4. The peptide forms a dimeric
      coiled coil through its 33 C-terminal residues. A(2) is a designed 30-residue
      dimeric coiled coil whose folding is induced by low pH [Durr, E., Jelesarov, I.,
      and Bosshard, H. R. (1999) Biochemistry 38, 870-880]. Folding and unfolding were
      assessed under identical native buffer conditions so that the microscopic
      reversibility applied and the transition state was the same for folding and
      unfolding. The time course of folding was followed from the self-quenching of a C
      terminal fluorescent label (Texas Red). The overall folding of both peptides is
      enthalpy-driven and opposed by a loss of entropy. The main energetic changes
      occur after the system has passed the transition state. In the folding of
      C62GCN4, only 10-20% of the heat capacity change is attained between the
      monomeric state and the dimeric transition state. For coiled coil A(2), the
      fractional heat capacity change preceding the transition state is 30-40%. The
      results indicate that the activated states of folding of coiled coils are not
      well structured and differ considerably from the folded coiled coil conformation.
      These findings are in agreement with a rate-limiting transition state in which
      the coiled coil helices and the hydrophobic coiled coil interface are poorly
      developed.

PMID- 11297421
TI  - Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits
      A beta aggregation and toxicity.
AB  - Amyloid precursor protein (APP) is the source of the neurotoxic amyloid beta
      (Abeta) peptide associated with Alzheimer's disease. Apolipoprotein A-I (apoA-I),
      a constituent of high-density lipoprotein complexes, was identified by a yeast
      two-hybrid system as a strong and specific binding partner of full-length APP
      (APPfl). This association between apoA-I and APPfl was localized to the
      extracellular domain of APP (APPextra). Furthermore, the interaction between apoA
      I and APPfl was confirmed by coprecipitation using recombinant epitope-tagged
      APPextra and purified apoA-I. Several functional domains have been identified in
      APPextra, and we focused on a possible interaction between apoA-1 and the
      pathologically important Abeta peptide, because APPextra contains the
      nontransmembrane domain of Abeta. The binding between apoA-I and Abeta was
      saturable (K(d) = 6 nM), specific, and reversible. APPextra also competed with
      apoA-I for binding to Abeta. Direct evidence for this interaction was obtained by
      the formation of an SDS-resistant Abeta-apoA-I complex in polyacrylamide gels.
      Competitive experiments with apolipoprotein E (isoforms E2 and E4) showed that
      apoA-I had a higher binding affinity for Abeta. We also found that apoA-I
      inhibited the beta-sheet formation of Abeta with a mean inhibitory concentration
      close to that of alpha2-macroglobulin. Finally, we demonstrated that apoA-I
      attenuated Abeta-induced cytotoxicity. These results suggest apoA-I binds to at
      least one extracellular domain of APP and has a functional role in controlling
      Abeta aggregation and toxicity.

PMID- 11297422
TI  - NMR structural and dynamic characterization of the acid-unfolded state of
      apomyoglobin provides insights into the early events in protein folding.
AB  - Apomyoglobin forms a denatured state under low-salt conditions at pH 2.3. The
      conformational propensities and polypeptide backbone dynamics of this state have
      been characterized by NMR. Nearly complete backbone and some side chain resonance
      assignments have been obtained, using a triple-resonance assignment strategy
      tailored to low protein concentration (0.2 mM) and poor chemical shift
      dispersion. An estimate of the population and location of residual secondary
      structure has been made by examining deviations of (13)C(alpha), (13)CO, and
      (1)H(alpha) chemical shifts from random coil values, scalar (3)J(HN,H)(alpha)
      coupling constants and (1)H-(1)H NOEs. Chemical shifts constitute a highly
      reliable indicator of secondary structural preferences, provided the appropriate
      random coil chemical shift references are used, but in the case of acid-unfolded
      apomyoglobin, (3)J(HN,H)(alpha) coupling constants are poor diagnostics of
      secondary structure formation. Substantial populations of helical structure, in
      dynamic equilibrium with unfolded states, are formed in regions corresponding to
      the A and H helices of the folded protein. In addition, the deviation of the
      chemical shifts from random coil values indicates the presence of helical
      structure encompassing the D helix and extending into the first turn of the E
      helix. The polypeptide backbone dynamics of acid-unfolded apomyoglobin have been
      investigated using reduced spectral density function analysis of (15)N relaxation
      data. The spectral density J(omega(N)) is particularly sensitive to variations in
      backbone fluctuations on the picosecond to nanosecond time scale. The central
      region of the polypeptide spanning the C-terminal half of the E helix, the EF
      turn, and the F helix behaves as a free-flight random coil chain, but there is
      evidence from J(omega(N)) of restricted motions on the picosecond to nanosecond
      time scale in the A and H helix regions where there is a propensity to populate
      helical secondary structure in the acid-unfolded state. Backbone fluctuations are
      also restricted in parts of the B and G helices due to formation of local
      hydrophobic clusters. Regions of restricted backbone flexibility are generally
      associated with large buried surface area. A significant increase in J(0) is
      observed for the NH resonances of some residues located in the A and G helices of
      the folded protein and is associated with fluctuations on a microsecond to
      millisecond time scale that probably arise from transient contacts between these
      distant regions of the polypeptide chain. Our results indicate that the
      equilibrium unfolded state of apomyoglobin formed at pH 2.3 is an excellent model
      for the events that are expected to occur in the earliest stages of protein
      folding, providing insights into the regions of the polypeptide that
      spontaneously undergo local hydrophobic collapse and sample nativelike secondary
      structure.

PMID- 11297424
TI  - RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular
      responses.
AB  - To define the role of regulators of G-protein signaling (RGS) in chemoattractant
      mediated responses, RGS4 and the receptors for platelet-activating factor (PAFR),
      formylated peptides (FR), or interleukin-8 (CXCR1) were stably coexpressed in a
      rat basophilic leukemia (RBL-2H3) cell line. The data demonstrate that RGS4
      inhibited responses by PAFR (i.e., phosphoinositide (PI) hydrolysis, Ca2+
      mobilization) but not by FR or CXCR1. An N-terminal 33 amino acid deletion mutant
      of RGS4 (DeltaRGS4), deficient in GAP (GTPase activating protein) activity and
      plasma membrane localization, had no effect on either PAFR, FR, or CXCR1. RGS4,
      but not DeltaRGS4, also blocked phosphorylation of PAFR by platelet-activating
      factor (PAF) and, unexpectedly, by phorbol 12-myristate 13-acetate (PMA); it also
      blocked cross-phosphorylation by formylmethionylleucylphenylalanine (fMLP). A
      point mutant of RGS4 (N88S), deficient in GAP activity but not membrane
      localization, partially blocked PAFR phosphorylation but had no effect on PAFR
      mediated PI hydrolysis and Ca2+ mobilization. Truncation of the cytoplasmic tail
      of PAFR (mPAFR) resulted in a loss of its susceptibility to inhibition by RGS4.
      Taken together, the data indicate that of the receptors studied, RGS4 selectively
      inhibited responses to PAFR, which preferentially couples to Gq. At the level of
      expression studied, RGS4 did not inhibit FR or CXCR1 which activates Gi to
      transduce cellular signals. Since the tail-deleted mutant of PAFR was not
      affected by RGS4, and RGS4 blocked homologous as well as heterologous
      phosphorylation of this receptor, it is possible that RGS4 interferes sterically
      with the cytoplasmic tail of PAFR. Thus, in addition to stimulating the GTPase
      activity of Galpha, RGS4 prevents G protein activation by PAFR and the homologous
      and heterologous phosphorylation of this receptor.

PMID- 11297423
TI  - Hsp70s contain a specific sulfogalactolipid binding site. Differential aglycone
      influence on sulfogalactosyl ceramide binding by recombinant prokaryotic and
      eukaryotic hsp70 family members.
AB  - Specific 3'-sulfogalactolipid [SGL-sulfogalactosyl ceramide (SGCer) and
      sulfogalactosylglycerolipid (SGG)] binding is compared for hsp70s cloned from
      Helicobacter pylori, Haemophilus influenzae, Chlamydia trachomatis serovar E,
      Escherichia coli, murine male germ cells, and the hsp70-like extracellular domain
      within the sperm receptor from Strongylocentrotus purpuratus. This lectin
      activity, conserved among the different hsp70 family members, is modulated by the
      SGL aglycone. This is shown by differential binding to both SGC fatty acid
      homologues and 3'-sulfogalactolipid neoglycoproteins generated by coupling bovine
      serum albumin (BSA) and glycosyl ceramide acids synthesized by oxidation of the
      double bond of sphingosine. Eukaryotic hsp70s preferentially bound the SGCer
      fatty acid homologues SG(24)Cer, SG(18)Cer, and SG(20:OH)Cer, while prokaryotic
      hsp70s bound SG(18:1)Cer and SG(20:OH)Cer. Eukaryotic hsp70s bound SGCer-BSA and
      SG(24)Cer-BSA conjugates where the latter is the main constituent in SGCer-BSA,
      while prokaryotic hsp70s bound SG(20:OH)Cer-BSA. None of the hsp70s bound
      sulfogalactosyl sphingosine (SGSph) or SGSph-BSA, further demonstrating the
      important role of the aglycone. Although the primary SGL recognition domain of
      all hsp70s is conserved, we propose that aglycone organization differentially
      influences the interaction with the sub-site. Heterogeneous SGCer aglycone
      isoforms in cells and the differential in vitro binding of eukaryotic and
      prokaryotic hsp70s may relate to their different adhesin roles in vivo as
      mediators of germ cell and bacterial/host interactions, respectively.

PMID- 11297425
TI  - Entry of poliovirus into cells is blocked by valinomycin and concanamycin A.
AB  - Poliovirus contains a virus particle devoid of a lipid envelope that does not
      require an intact pH to enter into susceptible cells. Thus, the blockade of pH
      gradient generated in endosomes is not sufficient to impede the translocation of
      poliovirus particles to the cytoplasm, suggesting that translocation takes place
      at the plasma membrane. Measuring both viral protein synthesis and eIF4G-1
      cleavage mediated by poliovirus protease 2A has been used to monitor productive
      entry of poliovirus into cells. Translation of the input poliovirus RNA produces
      enough 2A(pro) to cleave eIF4G-1, providing a sensitive assay to estimate
      poliovirus RNA delivery to the cytoplasm followed by its translation. Combination
      of concanamycin A, a vacuolar proton-ATPase inhibitor, and valinomycin, an
      ionophore that promotes K(+) efflux from cells, powerfully prevented poliovirus
      infection. Moreover, modifying the ionic conditions of the culture medium
      (increasing the concentration of K(+) and decreasing the concentration of Na(+)),
      together with concanamycin A, also significantly interfered with poliovirus
      entry. These findings suggest that poliovirus RNA requires an intact
      concentration of K(+) ions inside the cells to be uncoated and to gain access to
      the cytoplasm. In addition, the actual contribution of concanamycin A (as well as
      other inhibitors of endocytosis) to the total inhibition of productive poliovirus
      entry points to the idea that at least some percentage of polioviral subparticles
      translocates from the endosomes.

PMID- 11297426
TI  - Titration of tertiapin-Q inhibition of ROMK1 channels by extracellular protons.
AB  - Tertiapin-Q (TPN(Q)), a honey bee toxin derivative, inhibits inward-rectifier
      K(+) channels by binding to their external vestibule. In the present study we
      found that TPN(Q) inhibition of the channels is profoundly affected by
      extracellular pH. This pH dependence mainly reflects titration of histidine
      residue 12 in TPN(Q) by extracellular protons, since it largely vanishes when the
      histidine residue is replaced with alanine. Not surprisingly, this alanine
      derivative of TPN(Q) binds to the channel with much lower affinity. Quantitative
      thermodynamic cycle analysis shows that deprotonation of the histidine residue
      reduces the TPN(Q)-ROMK1 binding energy by 1.6 kcal/mol. To eliminate pH
      sensitivity but retain high affinity, we derivatized TPN(Q) by replacing
      histidine 12 with lysine. This derivative-denoted tertiapin-KQ (TPN(KQ))-not only
      is practically insensitive to extracellular pH but also binds to the channel with
      even higher affinity than TPN(Q) at extracellular pH 7.6.

PMID- 11297428
TI  - Design and characterization of asparagine- and lysine-containing alanine-based
      helical peptides that bind selectively to A.T base pairs of oligonucleotides
      immobilized on a 27 mhz quartz crystal microbalance.
AB  - We have systematically designed and synthesized six kinds of 16-17 mer alanine
      based peptides containing four to six lysine (K) and one to four asparagine (N)
      residues to achieve the selective binding to A.T base pairs of DNA duplexes. The
      position and number of K and N residues were changed in the helical structure
      according to common features of the DNA-binding proteins, in which K and N
      residues are expected to interact electrostatically with phosphate groups and to
      interact with A.T base pairs by hydrogen bonding, respectively. The time courses
      of binding of these peptides to dA(30).dT(30) and dG(30).dC(30) duplexes
      immobilized on a 27 MHz quartz crystal microbalance (QCM) were studied in 10 mM
      phosphate buffer (pH 7.5) and 40 mM NaCl at 10 degrees C. The maximum binding
      amounts (Deltam(max)) on a nanogram scale and binding constants (K(a)) could be
      obtained from the frequency decrease (mass increase) of the oligonucleotide
      immobilized QCM. The conformation changes of the peptides upon binding to DNAs
      were monitored by circular dichroism (CD) spectroscopy. The four properly
      arranged N residues in the six-cationic K peptide, K6N4(d), resulted in a 5-fold
      higher affinity for A.T base pairs (K(a) = 5.9 x 10(5) M(-1)) than for G.C base
      pairs (K(a) = 1.2 x 10(5) M(-1)), and alpha-helices were clearly promoted by the
      binding to A.T base pairs from CD spectral changes.

PMID- 11297427
TI  - Protein kinase C phosphorylates nonmuscle myosin-II heavy chain from Drosophila
      but regulation of myosin function by this enzyme is not required for viability in
      flies.
AB  - Conventional myosins (myosin-IIs) generate forces for cell shape change and cell
      motility. Myosin heavy chain phosphorylation regulates myosin function in simple
      eukaryotes and may also be important in metazoans. To investigate this regulation
      in a complex eukaryote, we purified the Drosophila myosin-II tail expressed in
      Escherichia coli and showed that it was phosphorylated in vitro by protein kinase
      C(PKC) at serines 1936 and 1944, which are located in the nonhelical globular
      tail piece. These sites are close to a conserved serine that is phosphorylated in
      vertebrate, nonmuscle myosin-IIs. If the two serines are mutagenized to alanine
      or aspartic acid, phosphorylation no longer occurs. Using a 341 amino acid tail
      fragment, we show that there is no difference in the salt-dependent assembly of
      wild-type phosphorylated and mutagenized polypeptides. Thus, the nonmuscle myosin
      heavy chain in Drosophila, which is encoded by the zipper gene, appears to be
      similar to rabbit nonmuscle myosin-IIA. In vivo, we generated transgenic flies
      that expressed the various myosin heavy chain variants in a zipper null or near
      null genetic background. Like their wild-type counterparts, such variants are
      able to completely rescue the lethal phenotype due to severe zipper mutations.
      These results suggest that while the myosin-II heavy chain can be phosphorylated
      by PKC, regulation by this enzyme is not required for viability in Drosophila.
      Conservation during 530-1000 million years of evolution suggests that regulation
      by heavy chain phosphorylation may contribute to nonmuscle myosin-II function in
      some real, but minor, way.

PMID- 11297429
TI  - Conformational investigation of a cyclic enterobacterial common antigen employing
      NMR spectroscopy and molecular dynamics simulations.
AB  - The three-dimensional structure of a cyclic enterobacterial common antigen (ECA)
      having four trisaccharide repeating units has been investigated by NMR
      spectroscopy and molecular dynamics simulations. Three different NMR parameters
      were determined: (a) (1)H,(1)H cross-relaxation rates from NOE experiments were
      used for determination of proton-proton distances; (b) trans-glycosidic (3)J(C,H)
      scalar coupling constants analyzed via a Karplus-type relationship provided
      information on torsion angles; and (c) (1)H,(13)C one-bond dipolar couplings
      obtained in a dilute liquid-crystalline medium were interpreted in terms of the
      orientational order and molecular conformations. The molecular dynamics
      simulations of the dodecasaccharide were performed with explicit water and
      counterions, which are important factors that strongly influence molecular
      conformation. Subsequently, the results from computer simulation were used to
      generate a three-dimensional structure of the cyclic ECA which is consistent with
      the experimental NMR parameters.

PMID- 11297430
TI  - Altering the intermediate in the equilibrium folding of unmodified yeast tRNAPhe
      with monovalent and divalent cations.
AB  - The isothermal equilibrium folding of the unmodified yeast tRNA(Phe) is studied
      as a function of Na(+), Mg(2+), and urea concentration with hydroxyl radical
      protection, circular dichroism, and diethyl pyrocarbonate (DEPC) modification.
      These assays indicate that this tRNA folds in Na(+) alone. Similar to folding in
      Mg(2+), folding in Na(+) can be described by two transitions, unfolded-to
      intermediate-to-native. The I-to-N transition has a Na(+) midpoint of
      approximately 0.5 M and a Hill constant of approximately 4. Unexpectedly, the
      urea m-value, the dependence of free energy on urea concentration, for the I-to-N
      transition is significantly smaller in Na(+) than in Mg(2+), 0.4 versus 1.7 kcal
      mol(-1) M(-1), indicating that more structure is formed in the Mg(2+)-induced
      transition. DEPC modification indicates that the I state in Na(+)-induced folding
      contains all four helices of tRNA and the I-to-N transition primarily corresponds
      to the formation of the tertiary structure. In contrast, the intermediate in
      Mg(2+)-induced folding contains only three helices, and the I-to-N transition
      corresponds to the formation of the acceptor stem plus tertiary structure. The
      cation dependence of the intermediates arises from the differences in the
      stability of the acceptor stem and the tertiary structure. The acceptor stem is
      stable at a lower Na(+) concentration than required for the tertiary structure
      formation. The relative stability is reversed in Mg(2+) so that the acceptor stem
      and the tertiary structure form simultaneously in the I-to-N transition. These
      results demonstrate that formation of the RNA secondary structure can be
      independent or coupled to the formation of the tertiary structure depending on
      their relative stability in monovalent and divalent ions.

PMID- 11297431
TI  - Reaction of canine plasminogen with 6-aminohexanoate: a thermodynamic study
      combining fluorescence, circular dichroism, and isothermal titration calorimetry.
AB  - The thermodynamics of the binding of 6-aminohexanoate (6-AH) to dog glu
      plasminogen has been studied. Fluorescence titrations revealed four binding
      sites. Three yielded positive fluorescence changes on ligand binding; one yielded
      a negative fluorescence change. The fluorescence data gave no indication of
      cooperative interactions. Binding was studied using circular dichroism (CD). Near
      295 nm there were small changes associated with binding ligand. These were
      magnified at 235 nm, a wavelength that is mainly associated with tryptophan
      bands. The dissociation constants obtained from the fluorescence were applied to
      the CD data and fit quite well. Below 220 nm, there were no significant
      differences between samples with or without 6-AH and, therefore, no substantial
      change in the secondary structure of the protein. Isothermal titration
      calorimetry was used in combination with the binding constants from fluorescence
      to study the enthalpy and entropy contributions to 6-AH binding. The enthalpies
      of association for the four sites are all negative. Their absolute values are
      small for the tight sites and large for the weakest. -TDeltaS is negative for the
      tight sites and positive for the weakest. The binding of 6-AH to plasminogen is
      entropically driven for the two tightest sites and enthalpically driven for the
      weakest site. The binding of 6-AH to lys-plasminogen has been studied and differs
      slightly from binding to glu-plasminogen. Most importantly, the binding of 6-AH
      for the weak site goes from enthalpy- to entropy-driven as is found with the
      other sites.

PMID- 11297432
TI  - Hypochlorous acid produced by the myeloperoxidase system of human phagocytes
      induces covalent cross-links between DNA and protein.
AB  - Phagocytic oxidants have been implicated in tissue injury and oncogenesis, and
      their pathophysiological role in modifying nucleobases and amino acids has been
      widely explored. Their ability to cross-link proteins and DNA, however, has not
      been considered, even though reversible DNA-protein interactions are key to gene
      expression and to DNA replication and repair. In the current studies, we show
      that hypochlorous acid (HOCl), generated by the myeloperoxidase-hydrogen peroxide
      chloride system of phagocytes, cross-links single-stranded DNA-binding protein
      (SSB) to single-stranded oligonucleotides. Exposure of SSB and a homopolymer of
      radiolabeled thymidine (dT(40)) to HOCl resulted in the formation of a
      radiolabeled band with slower mobility than the free oligonucleotide, as
      determined by denaturing polyacrylamide gel electrophoresis. This radiolabeled
      band did not appear if the reaction mixture was treated with protease or
      nuclease, indicating that it represents a covalent complex of DNA and protein.
      Oligonucleotides of adenosine and cytidine behaved similarly to the thymidine
      oligonucleotide, demonstrating that they are also capable of participating in the
      cross-linking reaction. The covalent complex of radiolabeled dT(40) and SSB was
      also generated by chloramines and the complete myeloperoxidase-hydrogen peroxide
      chloride system. The enzymatic reaction required each component of the system and
      was inhibited by heme poisons and chloride-free conditions, implicating
      myeloperoxidase and HOCl. DNA-protein cross-links were generated in Escherichia
      coli exposed to HOCl, suggesting that double-stranded DNA is also a target for
      the reaction. These results indicate that long-lived chloramines and HOCl
      generated by myeloperoxidase can generate covalent DNA-protein cross-links that
      may contribute to the mutagenic and cytotoxic effects of phagocytes on microbial
      pathogens and host tissue.

PMID- 11297433
TI  - Direct measurement of acylenzyme hydrolysis demonstrates rate-limiting
      deacylation in cleavage of physiological sequences by the processing protease
      Kex2.
AB  - Saccharomyces cerevisiae Kex2 protease is the prototype for the family of
      eukaryotic proprotein convertases that includes furin, PC1/3, and PC2. These
      enzymes belong to the subtilase superfamily of serine proteases and are
      distinguished from degradative subtilisins by structural features and by their
      much more stringent substrate specificity. Pre-steady-state studies have shown
      that both Kex2 and furin exhibit an initial burst of 7-amino-4-methylcoumarin
      release in cleavage of peptidyl methylcoumarinamide substrates that are based on
      physiological cleavage sites. Thus, in cleavage of such substrates, formation of
      the acylenzyme intermediate is fast relative to some later step (deacylation or N
      terminal product release). This behavior is significant, because Kex2 also
      exhibits burst kinetics in cleavage of peptide bonds. k(cat) for cleavage of a
      tetrapeptidyl methylcoumarinamide substrate based on the physiological yeast
      substrate pro-alpha-factor exhibits a weak solvent isotope effect, but neither
      this isotope effect nor temperature dependence studies with this substrate
      conclusively identify the rate-limiting step for Kex2 cleavage of this substrate.
      We therefore developed an assay to measure deacylation directly by pulse-chase
      incorporation of H(2)(18)O in a rapid-quenched-flow mixer followed by mass
      spectrometric quantitation. The results given by this assay rule out rate
      limiting product release for cleavage of this substrate by Kex2. These
      experiments demonstrate that cleavage of the acylenzyme ester bond, as opposed to
      either the initial attack on the amide bond or product release, is rate-limiting
      for the action of Kex2 at physiological sequences. This work demonstrates a
      fundamental difference in the catalytic strategy of proprotein processing enzymes
      and degradative subtilisins.

PMID- 11297434
TI  - Cholesterol mobilization by free and lipid-bound apoAI(Milano) and apoAI(Milano)
      apoAII heterodimers.
AB  - Despite very low plasma levels of HDL, carriers of the apolipoprotein AI Arg173 -
      > Cys mutation apoAI(Milano) (AIM) have no apparent increase in risk for
      atherosclerotic vascular disease. HDL apolipoprotein species in AIM carriers
      include apoAI-AII heterodimers, previously found to confer the enhanced ability
      of tyrosyl radical-oxidized HDL to mobilize cholesterol for removal from cultured
      cells. To determine whether enhanced mobilization of cholesterol by apoprotein
      species in AIM explains a cardioprotective action of this mutation, we examined
      the ability of lipid-free and lipid-bound AIM and AIM-AII heterodimers to deplete
      cholesterol from cultured cells. Free AIM and AIM-AII heterodimers showed a
      decreased capacity to act as acceptors of cholesterol from cholesterol-loaded
      human fibroblasts compared with native apoAI but similar capacities to deplete
      fibroblasts of the pool of cholesterol available for esterification by acyl
      CoA:cholesterol acyltransferase (ACAT). Discoidal reconstituted HDL (rHDL)
      containing apoAI depleted both of these cholesterol pools more readily than AIM
      containing rHDL when compared at equivalent rHDL protein levels, but similar
      abilities of these rHDL to deplete cell cholesterol were seen when compared at
      equivalent phospholipid levels. Spherical rHDL generated using the whole lipid
      fraction of HDL and apoAI or AIM showed similar capacities to deplete total and
      ACAT-accessible cell cholesterol when compared at similar protein levels, but an
      increased capacity of AIM-containing particles was seen when compared at
      equivalent phospholipid levels. Unlike the apoAI-AII heterodimer in tyrosylated
      HDL, AIM-AII heterodimer-containing spherical rHDL showed no increased capacity
      to deplete either of these pools of cholesterol. These results suggest a similar
      or better capacity of native apoAI in lipid-free or lipid-bound form in discoidal
      rHDL to enhance the mobilization of cellular cholesterol when compared to AIM in
      its free or lipid-bound forms. Any increase in depletion of cellular cholesterol
      by lipid-bound AIM in spherical rHDL appears related to altered phospholipid
      binding rather than intrinsic cholesterol-mobilizing characteristics of this
      protein compared to native apoAI. The lack of major differences in these studies
      in cholesterol mobilization by native apoAI and AIM, or by apoAIM-AII
      heterodimers, suggests that any protection against atherosclerosis conferred by
      this mutation is likely related to other beneficial vascular effects of AIM.

PMID- 11297435
TI  - Evidence that SecB enhances the activity of SecA.
AB  - In Escherichia coli, SecA is a critical component of the protein transport
      machinery which powers the translocation process by hydrolyzing ATP and
      recognizing signal peptides which are the earmark of secretory proteins. In
      contrast, SecB is utilized by only a subset of preproteins to prevent their
      premature folding and chaperone them to membrane-bound SecA. Using purified
      components and synthetic signal peptides, we have studied the interaction of SecB
      with SecA and with SecA-signal peptide complexes in vitro. Using a chemical cross
      linking approach, we find that the formation of SecA-SecB complexes is
      accompanied by a decrease in the level of cross-linking of SecA dimers,
      suggesting that SecB induces a conformational change in SecA. Furthermore,
      functional signal peptides, but not dysfunctional ones, promote the formation of
      SecA-SecB complexes. SecB is also shown to directly enhance the ATPase activity
      of SecA in a concentration-dependent and saturable manner. To determine the
      biological consequence of this finding, the influence of SecB on the signal
      peptide-stimulated SecA/lipid ATPase was studied using synthetic peptides of
      varying hydrophobicity. Interestingly, the presence of SecB can sufficiently
      boost the response of signal peptides with moderate hydrophobicity such that it
      is comparable to the activity generated by a more hydrophobic peptide in the
      absence of SecB. The results suggest that SecB directly enhances the activity of
      SecA and provide a biochemical basis for the enhanced transport efficiency of
      preproteins in the presence of SecB in vivo.

PMID- 11297436
TI  - A Fourier transform infrared absorption difference spectrum associated with the
      reduction of A1 in photosystem I: are both phylloquinones involved in electron
      transfer?
AB  - Photoaccumulated Fourier transform infrared difference spectra associated with
      P700(+) and P700(+)A(1)(-) formation have been obtained using purified
      photosystem I particles from Synechocystis sp. PCC 6803. From these spectra, a
      difference spectrum associated with phylloquinone reduction (A(1)(-) - A(1)) has
      been calculated. Infrared absorption changes associated with both the loss of the
      ground state and formation of the anion radical are observed in the difference
      spectrum. Fourier transform infrared difference spectra obtained in various
      spectral regions indicate that two, structurally distinct phylloquinones are
      photoaccumulated. This could indicate that phylloquinones on both the PsaA and
      PsaB branches are involved in electron transfer, and that electron transfer is bi
      directional in photosystem I. It could also indicate an intrinsic structural
      heterogeneity in the A(1) binding site of the active branch. Several FTIR
      difference features taken together indicate that a glutamic acid residue (at
      position 699 or 702 on PsaA and/or 679 or 682 on PsaB) is perturbed upon A(1)
      anion formation. It is suggested that the protonation state of the perturbed
      glutamic acid residue is influenced by hydrogen bonding to a nearby tyrosine
      residue at position 696/676 on PsaA/PsaB.

PMID- 11297437
TI  - Does histidine 332 of the D1 polypeptide ligate the manganese cluster in
      photosystem II? An electron spin echo envelope modulation study.
AB  - The tetranuclear manganese cluster in photosystem II is ligated by one or more
      histidine residues, as shown by an electron spin echo envelope modulation (ESEEM)
      study conducted with [(15)N]histidine-labeled photosystem II particles isolated
      from the cyanobacterium Synechocystis sp. strain PCC 6803 [Tang, X.-S., Diner, B.
      A., Larsen, B. S., Gilchrist, M. L., Jr., Lorigan, G. A., and Britt, R. D. (1994)
      Proc. Natl. Acad. Sci. U.S.A. 91, 704-708]. One of these residues may be His332
      of the D1 polypeptide. Photosystem II particles isolated from the Synechocystis
      mutant D1-H332E exhibit an altered S(2) state multiline EPR signal that has more
      hyperfine lines and narrower splittings than the corresponding signal in wild
      type PSII particles [Debus, R. J., Campbell, K. A., Peloquin, J. M., Pham, D. P.,
      and Britt, R. D. (2000) Biochemistry 39, 470-478]. These D1-H332E PSII particles
      are also unable to advance beyond an altered S(2)Y(Z)(*) state, and the quantum
      yield for forming the S(2) state is very low, corresponding to an 8000-fold
      slowing of the rate of Mn oxidation by Y(Z)(*). These observations are consistent
      with His332 being close to the Mn cluster and modulating the redox properties of
      both the Mn cluster and tyrosine Y(Z). To determine if D1-His332 ligates the Mn
      cluster, we have conducted an ESEEM study of D1-H332E PSII particles. The
      histidyl nitrogen modulation observed near 5 MHz in ESEEM spectra of the S(2)
      state multiline EPR signal of wild-type PSII particles is substantially
      diminished in D1-H332E PSII particles. This result is consistent with ligation of
      the Mn cluster by D1-His332. However, alternate explanations are possible. These
      are presented and discussed.

PMID- 11297438
TI  - Kinetic and mutagenic characterization of the chromosomally encoded Salmonella
      enterica AAC(6')-Iy aminoglycoside N-acetyltransferase.
AB  - The chromosomally encoded aminoglycoside N-acetyltransferase, AAC(6')-Iy, from
      Salmonella enterica confers resistance toward a number of aminoglycoside
      antibiotics. The structural gene was cloned and expressed and the purified enzyme
      existed in solution as a dimer of ca. 17 000 Da monomers. Acetyl-CoA was the
      preferred acyl donor, and most therapeutically important aminoglycosides were
      substrates for acetylation. Exceptions are those aminoglycosides that possess a
      6'-hydroxyl substituent (e.g., lividomycin). Thus, the enzyme exhibited
      regioselective and exclusive acetyltransferase activity to 6'-amine-containing
      aminoglycosides. The enzyme exhibited Michaelis-Menten kinetics for some
      aminoglycoside substrates but "substrate activation" with others. Kinetic studies
      supported a random kinetic mechanism for the enzyme. The enzyme was inactivated
      by iodoacetamide in a biphasic manner, with half of the activity being lost
      rapidly and the other half more slowly. Tobramycin, but not acetyl-CoA, protected
      against inactivation. Each of the three cysteine residues (C70, C109, C145) in
      the wild-type enzyme were carboxamidomethylated by iodoacetamide. Cysteine 109 in
      AAC(6')-Iy is conserved in 12 AAC(6') enzyme sequences of the major class I
      subfamily. Surprisingly, mutation of this residue to alanine neither abolished
      activity nor altered the biphasic inactivation by iodoacetamide. The maximum
      velocity and V/K values for a number of aminoglycosides were elevated in this
      single mutant, and the kinetic behavior of substrates exhibiting linear vs
      nonlinear kinetics was reversed. Cysteine 70 in AAC(6')-Iy is either a cysteine
      or a threonine residue in all 12 AAC(6') enzymes of the major class I subfamily.
      The double mutant, C109A/C70A, was not inactivated by iodoacetamide. The double
      mutant exhibited large increases in the K(m) values for both acetyl-CoA and
      aminoglycoside substrates, and all aminoglycoside substrates exhibited Michaelis
      Menten kinetics. Solvent kinetic isotope effects on V/K were normal for the WT
      enzyme and inverse for the double mutant. We discuss a chemical mechanism and the
      likely rate-limiting steps for both the wild-type and mutant forms of the enzyme.

PMID- 11297439
TI  - Identification of the P-loop lysine as a metal ligand in the absence of
      nucleotide at catalytic site 3 of chloroplast F1-ATPase from Chlamydomonas
      reinhardtii.
AB  - Site-directed mutations were made to the phosphate-binding loop lysine in the
      beta-subunit of the chloroplast F(1)-ATPase in Chlamydomonas reinhardtii
      (betaK167) to investigate the participation of this residue in the binding of
      metal to catalytic site 3 in the absence of nucleotide. The cw-EPR spectra of
      VO(2+) bound to site 3 of CF(1)-ATPase from wild type and mutants revealed
      changes in metal ligation resulting from mutations to betaK167. The three-pulse
      ESEEM spectrum of the wild-type CF(1)-ATPase with VO(2+) bound to site 3 shows an
      equatorially coordinating (14)N from an amine. The ESEEM spectra of the mutants
      do not show evidence of an equatorially coordinating amine group. The results
      presented here show that, in the absence of nucleotide, betaK167 is a ligand to
      the metal bound at catalytic site 3, suggesting a regulatory role for the P-loop
      lysine in addition to its known role in catalysis.

PMID- 11297440
TI  - Influence of flanking sequence context on the mutagenicity of acetylaminofluorene
      derived DNA adducts in mammalian cells.
AB  - Site-specifically modified oligodeoxynucleotides were used to explore the
      influence of neighboring base sequence context on the mutagenic potential of N
      (deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) and N-(deoxyguanosin-8-yl)-2
      aminofluorene (dG-AF) in mammalian cells. Oligodeoxynucleotides
      ((5)(')TCCTCCTNXNCTCTC, where X is dG-AAF, dG-AF, or dG and N is C, A, G, or T)
      with different bases flanking the lesion were incorporated into a single-strand
      shuttle plasmid vector and used to establish the mutational frequency and
      specificity of dG-AAF and dG-AF adducts in simian kidney (COS-7) cells. Vectors
      containing dG-AAF promote preferential incorporation of dCMP at the site of the
      lesion; misincorporation of dAMP and dTMP also was observed. Mutational
      frequencies range from 11 to 23%. High mutational frequencies (18-23%) were
      observed when G or T was positioned 5' to dG-AAF and a lower frequency (11%) when
      C was 5' to the lesion. dCMP was predominantly incorporated opposite the dG-AF
      adduct when C, A, or T was 5' to the lesion; dAMP and dTMP were misincorporated
      at a frequency of 2-4%. With G 5' to the lesion, the overall mutational frequency
      for dG-AF ranged between 11 and 70%; the highest value occurred when C was the 3'
      flanking base, and the predominant mutation event was G --> T transversion (59%).
      We conclude from these experiments that dG-AAF and dG-AF promote G --> T
      transversions and G --> A transitions in mammalian cells. The mutational
      frequency and specificity of dG-AF vary significantly, depending on the nature of
      the bases flanking the lesion.

PMID- 11297441
TI  - A conformational change in the "loop E-like" motif of the hairpin ribozyme is
      coincidental with domain docking and is essential for catalysis.
AB  - The catalysis of site-specific RNA cleavage and ligation by the hairpin ribozyme
      requires the formation of a tertiary interaction between two independently folded
      internal loop domains, A and B. Within the B domain, a tertiary structure has
      been identified, known as the loop E motif, that has been observed in many
      naturally occurring RNAs. One characteristic of this motif is a partial cross
      strand stack of a G residue on a U residue. In a few cases, including loop B of
      the hairpin ribozyme, this unusual arrangement gives rise to photoreactivity. In
      the hairpin, G21 and U42 can be UV cross-linked. Here we show that docking of the
      two domains correlates very strongly with a loss of UV reactivity of these bases.
      The rate of the loss of photoreactivity during folding is in close agreement with
      the kinetics of interdomain docking as determined by hydroxyl-radical
      footprinting and fluorescence resonance energy transfer (FRET). Fixing the
      structure of the complex in the cross-linked form results in an inability of the
      two domains to dock and catalyze the cleavage reaction, suggesting that the
      conformational change is essential for catalysis.

PMID- 11297442
TI  - Activation of class III ribonucleotide reductase by flavodoxin: a protein radical
      driven electron transfer to the iron-sulfur center.
AB  - In its active form, Escherichia coli class III ribonucleotide reductase homodimer
      alpha(2) relies on a protein free radical located on the Gly(681) residue of the
      alpha polypeptide. The formation of the glycyl radical, namely, the activation of
      the enzyme, involves the concerted action of four components: S
      adenosylmethionine (AdoMet), dithiothreitol (DTT), an Fe-S protein called beta or
      "activase", and a reducing system consisting of NADPH, NADPH:flavodoxin
      oxidoreductase, and flavodoxin (fldx). It has been proposed that a reductant
      serves to generate a reduced [4Fe-4S](+) cluster absolutely required for the
      reductive cleavage of AdoMet and the generation of the radical. Here, we suggest
      that the one-electron reduced form of flavodoxin (SQ), the only detectable
      product of the in vitro enzymatic reduction of flavodoxin, can support the
      formation of the glycyl radical. However, the redox potential of the Fe-S center
      of the enzyme is shown to be approximately 300 mV more negative than that of the
      SQ/fldx couple and not shifted to a more positive value by AdoMet binding. It is
      also more negative than that of the HQ/SQ couple, HQ being the fully reduced form
      of flavodoxin. Our interpretation is that activation of ribonucleotide reductase
      occurs through coupling of the reduction of the Fe-S center by flavodoxin to two
      thermodynamically favorable reactions, the oxidation of the cluster by AdoMet,
      yielding methionine and the 5'-deoxyadenosyl radical, and the oxidation of the
      glycine residue to the corresponding glycyl radical by the 5'-deoxyadenosyl
      radical. The second reaction plays the major role on the basis that a Gly-to-Ala
      mutation results in a greatly decreased production of methionine.

PMID- 11297443
TI  - Excitation trap approach to analyze size and pigment-pigment coupling:
      reconstitution of LH1 antenna of Rhodobacter sphaeroides with Ni-substituted
      bacteriochlorophyll.
AB  - Replacement of the central Mg in chlorophylls by Ni opens an ultrafast (tens of
      femtoseconds time range) radiationless de-excitation path, while the principal
      ground-state absorption and coordination properties of the pigment are retained.
      A method has been developed for substituting the native bacteriochlorophyll a by
      Ni-bacteriochlorophyll a ([Ni]-BChl) in the light harvesting antenna of the core
      complex (LH1) from the purple bacterium, Rhodobacter (Rb.) sphaeroides, to
      investigate its unit size and excited state properties. The components of the
      complex have been extracted with an organic solvent from freeze-dried membranes
      of an LH1-only strain of Rb. sphaeroides and transferred into the micelles of n
      octyl-beta-glucopyranoside (OG). Reconstitution was achieved by solubilization in
      3.4% OG, followed by dilution, yielding a complex nearly identical to the native
      one, in terms of absorption, fluorescence, and circular dichroism spectra as well
      as energy transfer efficiency from carotenoid to bacteriochlorophyll. By adding
      increasing amounts of [Ni]-BChl to the reconstitution mixture, a series of LH1
      complexes was obtained that contain increasing levels of this efficient
      excitation trap. In contrast to the nearly unchanged absorption, the presence of
      [Ni]-BChl in LH1 markedly affects the emission properties. Incorporation of only
      3.2 and 20% [Ni]-BChl reduces the emission by 50% and nearly 100%, respectively.
      The subnanosecond fluorescence kinetics of the complexes were monoexponential,
      with the lifetime identical to that of the native complex, and its amplitude
      decreasing in parallel with the steady-state fluorescence yield. Quantitative
      analysis of the data, based on a Poisson distribution of the modified pigment in
      the reconstituted complex, suggests that the presence of a single excitation trap
      per LH1 unit suffices for efficient emission quenching and that this unit
      contains 20 +/- 1 BChl molecules.

PMID- 11297444
TI  - Probing functional perfection in substructures of ribonuclease T1: double
      combinatorial random mutagenesis involving Asn43, Asn44, and Glu46 in the guanine
      binding loop.
AB  - Combinatorial random mutageneses involving either Asn43 with Asn44 (set 1) or
      Glu46 with an adjacent insertion (set 2) were undertaken to explore the
      functional perfection of the guanine recognition loop of ribonuclease T(1) (RNase
      T(1)). Four hundred unique recombinants were screened in each set for their
      ability to enhance enzyme catalysis of RNA cleavage. After a thorough selection
      procedure, only six variants were found that were either as active or more active
      than wild type which included substitutions of Asn43 by Gly, His, Leu, or Thr, an
      unplanned Tyr45Ser substitution and Glu46Pro with an adjacent Glu47 insertion.
      Asn43His-RNase T(1) has the same loop sequence as that for RNases Pb(1) and
      Fl(2). None of the most active mutants were single substitutions at Asn44 or
      double substitutions at Asn43 and Asn44. A total of 13 variants were purified,
      and these were subjected to kinetic analysis using RNA, GpC, and ApC as
      substrates. Modestly enhanced activities with GpC and RNA involved both k(cat)
      and K(M) effects. Mutants having low activity with GpC had proportionately even
      lower relative activity with RNA. Asn43Gly-RNase T(1) and all five of the
      purified mutants in set 2 exhibited similar values of k(cat)/K(M) for ApC which
      were the highest observed and about 10-fold that for wild type. The specificity
      ratio [(k(cat)/K(M))(GpC)/(k(cat)/K(M))(ApC)] varied over 30 000-fold including a
      10-fold increase [Asn43His variant; mainly due to a low (k(cat)/K(M))(ApC)] and a
      3000-fold decrease (Glu46Ser/(insert)Gly47 variant; mainly due to a low
      (k(cat)/K(M))(GpC)) as compared with wild type. It is interesting that k(cat)
      (GpC) for the Tyr45Ser variant was almost 4-fold greater than for wild type and
      that Pro46/(insert)Glu47 RNase T(1) is 70-fold more active than the permuted
      variant (insert)Pro47-RNase T(1) which has a conserved Glu46. In any event, the
      observation that only 6 out of 800 variants surveyed had wild-type activity
      supports the view that functional perfection of the guanine recognition loop of
      RNase T(1) has been achieved.

PMID- 11297446
TI  - Covalently induced activation of the delta opioid receptor by a fluorogenic
      affinity label, 7'-(phthalaldehydecarboxamido)naltrindole (PNTI).

PMID- 11297447
TI  - Discovery and optimization of a novel series of thrombin receptor (par-1)
      antagonists: potent, selective peptide mimetics based on indole and indazole
      templates.

PMID- 11297448
TI  - Substituted pyrazolopyridines as potent and selective PDE5 inhibitors: potential
      agents for treatment of erectile dysfunction.

PMID- 11297449
TI  - Molecular models of N-benzyladriamycin-14-valerate (AD 198) in complex with the
      phorbol ester-binding C1b domain of protein kinase C-delta.
AB  - N-Benzyladriamycin-14-valerate (AD 198) is a semisynthetic anthracycline with
      experimental antitumor activity superior to that of doxorubicin (DOX). AD 198,
      unlike DOX, only weakly binds DNA, is a poor inhibitor of topoisomerase II, and
      circumvents anthracycline-resistance mechanisms, suggesting a unique mechanism of
      action for this novel analogue. The phorbol ester receptors, protein kinase C
      (PKC) and beta2-chimaerin, were recently identified as selective targets for AD
      198 in vitro. In vitro, AD 198 competes with [3H]PDBu for binding to a peptide
      containing the isolated C1b domain of PKC-delta (deltaC1b domain). In the present
      study molecular modeling is used to investigate the interaction of AD 198 with
      the deltaC1b domain. Three models are identified wherein AD 198 binds into the
      groove formed between amino acid residues 6-13 and 21-27 of the deltaC1b domain
      in a manner similar to that reported for phorbol-13-acetate and other ligands of
      the C1 domain. Two of the identified models are consistent with previous
      experimental data demonstrating the importance of the 14-valerate side chain of
      AD 198 in binding to the C1 domain as well as current data demonstrating that
      translocation of PKC-alpha to the membrane requires the 14-valerate substituent.
      In this regard, the carbonyl of the 14-valerate participates in hydrogen bonding
      to the deltaC1b while the acyl chain is positioned for stabilization of the
      membrane-bound protein-ligand complex in a manner analogous to the acyl chains of
      the phorbol esters. These studies provide a structural basis for the interaction
      of AD 198 with the deltaC1b domain and a starting point for the rational design
      of potential new drugs targeting PKC and other proteins with C1 domains.

PMID- 11297450
TI  - Detailed analysis of scoring functions for virtual screening.
AB  - We present a comprehensive study of the performance of fast scoring functions for
      library docking using the program FlexX as the docking engine. Four scoring
      functions, among them two recently developed knowledge-based potentials, are
      evaluated on seven target proteins whose binding sites represent a wide range of
      size, form, and polarity. The results of these calculations give valuable insight
      into strengths and weaknesses of current scoring functions. Furthermore, it is
      shown that a well-chosen combination of two of the tested scoring functions leads
      to a new, robust scoring scheme with superior performance in virtual screening.

PMID- 11297451
TI  - Estimation of binding affinities for selective thrombin inhibitors via Monte
      Carlo simulations.
AB  - Monte Carlo simulations have been performed on a series of 20 active-site
      directed thrombin inhibitors to determine the interactions and energetics
      associated with the binding of these compounds. Physicochemical descriptors of
      potential value in the prediction of binding affinities were averaged during
      simulations of each inhibitor unbound in water and bound to thrombin. Regression
      equations based on 3-5 descriptors are able to reproduce the experimental binding
      affinities, which cover a 7 kcal/mol range, with rms errors of 1.0-1.3 kcal/mol,
      and yield correlation coefficients, r(2), of 0.7-0.8. On the basis of these
      results, the quantities most important in determining the binding affinities are:
      (1) the enhancement of van der Waals interactions in going from solution to the
      bound state, (2) the intramolecular strain induced in the inhibitor upon binding,
      (3) the number of hydrogen bonds lost in the binding process, and (4) the number
      of rotatable bonds in the inhibitor. The descriptors are physically reasonable
      and, in combination with the insights gained from analysis of the simulation
      structures, suggest directions for the development of improved thrombin
      inhibitors.

PMID- 11297452
TI  - Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists
      at group I metabotropic glutamic acid receptors.
AB  - Using ibotenic acid (2) as a lead, two series of 3-isoxazolol amino acid ligands
      for (S)-glutamic acid (Glu, 1) receptors have been developed. Whereas analogues
      of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [AMPA, (RS)-3]
      interact selectively with ionotropic Glu receptors (iGluRs), the few analogues of
      (RS)-2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid [HIBO, (RS)-4] so far known
      typically interact with iGluRs as well as metabotropic Glu receptors (mGluRs). We
      here report the synthesis and pharmacology of a series of 4-substituted analogues
      of HIBO. The hexyl analogue 9 was shown to be an antagonist at group I mGluRs.
      The effects of 9 were shown to reside exclusively in (S)-9 (K(b) = 30 microM at
      mGlu(1) and K(b) = 61 microM at mGlu(5)). The lower homologue of 9, compound 8,
      showed comparable effects at mGluRs, but 8 also was a weak agonist at the AMPA
      subtype of iGluRs. Like 9, the higher homologue, compound 10, did not interact
      with iGluRs, but 10 selectively antagonized mGlu(1) (K(b) = 160 microM) showing
      very weak antagonist effect at mGlu(5) (K(b) = 990 microM). The phenyl analogue
      11 turned out to be an AMPA agonist and an antagonist at mGlu(1) and mGlu(5), and
      these effects were shown to originate in (S)-11 (EC(50) = 395 microM, K(b) = 86
      and 90 microM, respectively). Compound 9, administered icv, but not sc, was shown
      to protect mice against convulsions induced by N-methyl-D-aspartic acid (NMDA).
      Compounds 9 and 11 were resolved using chiral HPLC, and the configurational
      assignments of the enantiomers were based on X-ray crystallographic analyses.

PMID- 11297453
TI  - Development of new carboxylic acid-based MMP inhibitors derived from
      functionalized propargylglycines.
AB  - A series of carboxylic acids were prepared from a propargylglycine scaffold and
      tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR
      for the series is reported for four enzymes within the MMP family. The inhibitors
      were typically potent against collagenase-3 (MMP-13) and gelatinase A (MMP-2),
      while they spared collagenase-1 (MMP-1) and only moderately inhibited stromelysin
      (MMP-3). Compound 40 represents a typical inhibition profile of a compound with
      reasonable potency. Introduction of polar groups was required in order to
      generate inhibitors with acceptable water solubility, and this often resulted in
      a loss of potency as in compound 63. High serum protein binding proved to be a
      difficult hurdle with many compounds such as 48 showing >99% binding. Some
      compounds such as 64 displayed approximately 90% binding, but no reliable method
      was discovered for designing molecules with low protein binding. Finally,
      selected data regarding the pharmacokinetic behavior of these compounds is
      presented.

PMID- 11297454
TI  - Flexible estrogen receptor modulators: design, synthesis, and antagonistic
      effects in human MCF-7 breast cancer cells.
AB  - Although many series of estrogen receptor antagonists continue to be produced,
      the majority are direct structural analogues of existing modulators. To examine
      the tolerance of the estrogen receptor toward flexible ligands, a series of novel
      flexible estrogen receptor antagonists were prepared and their antiproliferative
      effects on human MCF-7 breast tumor cells investigated. Each of these compounds
      deviated from the traditional triphenylethylene backbone associated with common
      tamoxifen analogues through the introduction of a flexible methylene (benzylic)
      spacing group between one of the aryl rings and the ethylene group and through
      variations in the basic side chain moiety. The compounds prepared, when assayed
      in conjunction with a tamoxifen standard, demonstrated high potency in
      antiproliferative assays against an MCF-7 human breast cancer cell line with low
      cytotoxicity and high binding affinity. A computational study was undertaken to
      investigate the compounds' potential interactions with specific residues within
      the human estrogen receptor alpha ligand-binding domain (ER-LBD), predicting
      these compounds bind in an antiestrogenic fashion within the ER-LBD and interact
      with those important residues previously identified in the structures of ER-LBD
      agonist/antagonist cocrystals. These compounds further illustrate the eclectic
      nature of the estrogen receptor in terms of ligand flexibility tolerance.

PMID- 11297455
TI  - Cardioselective K(ATP) channel blockers derived from a new series of m
      anisamidoethylbenzenesulfonylthioureas.
AB  - Sulfonylthioureas exhibiting cardioselective blockade of ATP-sensitive potassium
      channels (K(ATP) channels) were discovered by stepwise structural variations of
      the antidiabetic sulfonylurea glibenclamide. As screening assays, reversal of
      rilmakalim-induced shortening of the cardiac action potential in guinea pig
      papillary muscles was used to probe for activity on cardiac K(ATP) channels as
      the target, and membrane depolarization in CHO cells stably transfected with
      hSUR1/hKir6.2 was used to probe for unwanted side effects on pancreatic K(ATP)
      channels. Changing glibenclamide's para-arrangement of substituents in the
      central aromatic ring to a meta-pattern associated with size reduction of the
      substituent at the terminal nitrogen atom of the sulfonylurea moiety was found to
      achieve cardioselectivity. An additional change from a sulfonylurea moiety to a
      sulfonylthiourea moiety along with an appropriate substituent in the ortho
      position of the central aromatic system was a successful strategy to further
      improve potency on the cardiac K(ATP) channel. Among this series of
      sulfonylthioureas HMR1883, 1-[5-[2-(5-chloro-o-anisamido)ethyl]-2
      methoxyphenyl]sulfonyl-3-methylthiourea, and its sodium salt HMR1098 were
      selected for development and represent a completely new therapeutic approach
      toward the prevention of life-threatening arrhythmias and sudden cardiac death in
      patients with coronary heart disease.

PMID- 11297456
TI  - Progress toward the development of a safe and effective agent for treating
      reentrant cardiac arrhythmias: synthesis and evaluation of ibutilide analogues
      with enhanced metabolic stability and diminished proarrhythmic potential.
AB  - A series of ibutilide analogues with fluorine substituents on the heptyl side
      chain was prepared and evaluated for class III antiarrhythmic activity, metabolic
      stability, and proarrhythmic potential. It was found that fluorine substituents
      stabilized the side chain to metabolic oxidation. Many of the compounds also
      retained the ability to increase the refractoriness of cardiac tissue at both
      slow and fast pacing rates. The potential for producing polymorphic ventricular
      tachycardia in the rabbit model was dependent on the chirality of the benzylic
      carbon. The S-enantiomers generally had less proarrhythmic activity than the
      corresponding racemates. One compound from this series (45E, trecetilide
      fumarate) had excellent antiarrhythmic activity and metabolic stability and was
      devoid of proarrhythmic activity in the rabbit model. It was chosen for further
      development.

PMID- 11297457
TI  - Synthesis and biodistribution of a new oxo-technetium-99m bis(aminothiol) complex
      as a potential melanoma tracer.
AB  - [123I]-N-(2-Diethylaminoethyl)-4-iodobenzamide (123I-BZA) has been the best
      scintigraphic agent described so far for malignant melanoma and ocular melanoma
      diagnosis. We replaced 123I by the more convenient radioisotope 99mTc and
      synthesized four bis(aminoethanethiol) derivatives. We describe the synthesis of
      a new oxo-technetium complex (TcO-Cf), prepared in very high yield (radiochemical
      yield > 95%), that exhibits an affinity for the pigmented tumor cells. This
      complex was evaluated in vivo in mice bearing C57Bl6 murine melanoma. After
      injection, a rapid decrease in the radioactivity levels was noted for all tissues
      and organs except for eyes (1.26 %ID/g at 1 h and 2.69 %ID/g at 24 h
      postinjection) and the tumor (1.19 %ID/g at 1 h and 0.80 %ID/g at 24 h
      postinjection), suggesting a specific in vivo binding of this complex to the
      pigmented cells. These results were compared with those already published for
      three other technetium-99m bis(aminothiol) complexes with benzamide derivatives.

PMID- 11297458
TI  - Postoperative Proprionobacterium acnes endophthalmitis.

PMID- 11297461
TI  - Postoperative proprionibacterium acnes endophthalmitis.

PMID- 11297463
TI  - High-resistance wind instruments and IOP.

PMID- 11297465
TI  - Disinfection of vacuum control manifold to prevent postoperative endophthalmitis.

PMID- 11297467
TI  - Micro-Reflux [correction of Micro-Reflex] Test vs. the Kleenex test.

PMID- 11297469
TI  - Measurement of blood-aqueous barrier breakdown.

PMID- 11297471
TI  - Orbital implants in postenucleation retinoblastoma.

PMID- 11297473
TI  - The choice of glaucoma.

PMID- 11297472
TI  - Agar melting with microwave.

PMID- 11297474
TI  - Quality of life associated with unilateral and bilateral good vision.
AB  - OBJECTIVE: To ascertain with patient preference-based methodology whether
      individuals with good visual acuity (20/20-20/25) in one eye have the same
      quality of life as individuals with good vision in both eyes. DESIGN: Cross
      sectional comparative study. PARTICIPANTS: Consecutive patients seen in
      comprehensive ophthalmic and vitreoretinal practices with known ocular disease
      and good visual acuity (20/20 or 20/25) in one or both eyes. METHODS:
      Standardized patient interview. MAIN OUTCOME MEASURES: Time tradeoff and utility
      analysis values. RESULTS: The mean time tradeoff utility value in 81 patients
      with good visual acuity in one eye was 0.89 (standard deviation, 0.17; 95%
      confidence interval, 0.85-0.93), whereas the mean value in 66 patients with good
      vision in both eyes was 0.97 (standard deviation, 0.05; 95% confidence interval,
      0.97-0.99). The difference between the means of the utility values in these two
      groups was significant using multiple linear regression (P = 0.001). CONCLUSIONS:
      From the patient preference-based point of view, individuals with ocular disease
      and good visual acuity in both eyes appear to have a higher time tradeoff utility
      value, and thus a better associated quality of life, than those with good visual
      acuity in only one eye.

PMID- 11297476
TI  - Laser cataract surgery : A prospective clinical evaluation of 1000 consecutive
      laser cataract procedures using the Dodick photolysis Nd:YAG system.
AB  - BACKGROUND: To evaluate the safety and efficacy associated with the clinical use
      of a Q-switched neodymium:yttrium-aluminum-garnet (ND:YAG) laser for cataract
      removal. DESIGN: Multicenter, prospective, noncomparative case series.
      PARTICIPANTS/INTERVENTION: A total of 1000 consecutive eyes underwent cataract
      extraction with the photolysis Q-switched ND:YAG laser at 12 international
      clinical sites. MAIN OUTCOME MEASURES: Visual acuity improvement; total energy
      used; mean operative time for cataract removal; complications, both
      intraoperative and postoperative; with a minimum follow-up of 3 months. RESULTS:
      The mean values were visual acuity improvement from 20/70.2 to 20/24.4. Mean
      intraocular energy used was 5.65 J per case. Mean operative photolysis time among
      the surgeons was for up to +1 nuclear sclerosis, 2.15 minutes; up to +2 nuclear
      sclerosis, 4.8 minutes; and for up to +3 nuclear sclerosis, 9.8 minutes. Three
      cases were completed by intraocular lens implantation through the original sub-2
      mm incision, using a prefolded, by dehydration, acrylic intraocular lens. Minor
      complications were encountered in 18 cases. CONCLUSIONS: These data suggest this
      photolysis laser technology may be a safe and effective alternative for cataract
      extraction in human eyes. By use of small clear cornea incisions, the ability to
      perform cataract extraction and intraocular lens implantation with incisions less
      than 2 mm has been shown for the first time.

PMID- 11297478
TI  - The role of matrix metalloproteinases in ulcerative keratolysis associated with
      perioperative diclofenac use.
AB  - OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) in the
      pathogenesis of ulcerative keratolysis associated with topical use of generic
      diclofenac preoperatively and postoperatively. To characterize the inflammatory
      response of the cornea in this case of ulcerative keratolysis. DESIGN: Case
      report with clinicopathologic correlation. MAIN OUTCOME MEASURES: Corneal culture
      for microbial growth. Clinical and histopathologic examinations including routine
      histolopathologic, immunofluorescent, and immunohistochemical studies. RESULTS:
      Microscopic examination of the corneal button disclosed fibrinous material with
      neutrophils and mononuclear inflammatory cells. The corneal epithelial basement
      membrane was irregularly thickened and patchy. Immunohistochemical staining
      detected weak staining of MMP-1 and a strong presence of MMP-8 in the epithelium.
      MMP-8 and 9 were also present in areas of leukocytic infiltration. MMP-2 appeared
      in a few stromal cells. Macrophages and leukocytes were the predominant
      infiltrating cells. CONCLUSIONS: A nonspecific inflammatory response occurred in
      this case of ulcerative keratolysis. Corneal epithelial cells are capable of
      secreting MMP-1 and 8 and may participate in the stromal degradation and repair
      process of the ulcerative keratolysis associated with topical nonsteroidol
      antiinflammatory use.

PMID- 11297479
TI  - Laser in situ keratomileusis-induced optic neuropathy.
AB  - OBJECTIVE: To report a case of bilateral optic neuropathy after bilateral laser
      assisted in situ keratomileusis (LASIK) surgery. DESIGN: Observational case
      report. METHODS: Complete eye examination with detailed evaluation of the optic
      nerve, detailed medical history, stereo disc photographs, GDx Nerve Fiber
      Analyzer testing, Humphrey 24-2 SITA visual field testing, diurnal intraocular
      pressure measurement, serologic evaluation, and magnetic resonance imaging of the
      brain and orbits. MAIN OUTCOME MEASURES: Optic nerve status, visual field status,
      and visual acuity. RESULTS: A subject with previously healthy optic nerves had
      bilateral optic neuropathy develop after LASIK surgery. This neuropathy
      manifested with a subjective decrease in visual field, normal visual acuity,
      normal color vision, relative afferent pupillary defect, increased cupping of the
      optic nerve with focal neuroretinal rim defects, decreased nerve fiber layer
      thickness, and nerve fiber bundle-type visual field defects. The subject had no
      other risk factors for optic neuropathy. No other cause of neuropathy was
      identified. CONCLUSIONS: Optic neuropathy is a potential vision-threatening
      complication of LASIK surgery. This complication may be due to barotrauma or
      ischemia related to extreme elevation of intraocular pressure by the suction
      ring. Careful examination of the optic nerve before and after LASIK surgery is
      warranted.

PMID- 11297480
TI  - Posterior corneal curvature changes after myopic laser in situ keratomileusis.
AB  - OBJECTIVE: To assess the posterior corneal power and asphericity changes after
      myopic laser in situ keratomileusis (LASIK) and to correlate these changes with
      the amount of correction and the residual stromal bed thickness. DESIGN:
      Prospective nonrandomized (self-controlled) comparative study. PARTICIPANTS:
      Fifty-seven eyes of 14 women and 15 men, mean age at the time of surgery 33 +/- 9
      (range, 19-53) years with a spherical equivalent (SEQ) of -1.00 to -15.50 (mean, 
      5.07 +/- 2.81) diopters (DI). INTERVENTION: All procedures were performed with
      the Keratom II Coherent-Schwind excimer laser and and the Moria Model One
      microkeratome (150-microm head). Subjective refractometry, Orbscan slit scanning
      corneal topography analysis and pachymetry were performed before and 3 months
      after LASIK for myopia (n=35, -1.00 to -15.50 D, mean -4.75 +/- -3.07 D) or
      myopic astigmatism (n=22, sphere 0.00 to -9.75 D, mean -4.75 +/- 2.36 D; cylinder
      -0.75 to -3.50 D, mean -1.68 +/- 0.86 D). Intended ablation depth ranged from 12
      to 108 (mean, 48 +/- 22) microm. Topographic raw data were decomposed into a set
      of Zernike polynomials as published in detail previously, and parameters
      potentially indicative for detection of a "mild keratectasia" were derived. MAIN
      OUTCOME MEASURES: Posterior central corneal power and asphericity before and
      after LASIK were compared, and changes of these variables were correlated with
      the SEQ change (deltaSEQ)and the residual corneal bed thickness RBT). RESULTS:
      The mean RBT after LASIK was 280 +/- 42 microm. Overall, change of posterior
      power (-6.28 +/- 0.22 D/ -6.39 +/- 0.23 D, P=0.02) was statistically significant
      and change of asphericity (0.98 +/-0.07/1.14 +/- -.20, P<0.0001) was highly
      significant. In eyes with RBT < or =250 microm, the average change of posterior
      central power (-0.20 +/- 0.10 D vs. -0.08 +/- 0.18 D) was significantly greater
      than in eyes with RBT >250 microm (P=0.003). The change of posterior corneal
      power correlated significantly with deltaSEQ (P=0.004) and the RBT (P=0.002).
      CONCLUSIONS: Increased negative keratometric diopters and oblate asphericity of
      the posterior corneal curvature suggest that mild "keratectesia" of the cornea
      may be common early after LASIK. Further stuudies with longer follow-up are
      required to clarify whether this biomechanical deformation is progressive and
      whether a residual bed thickness of >250 microm can completely prevent it.

PMID- 11297482
TI  - Understanding refraction and accommodation through "retinal imaging" aberrometry:
      a case report.
AB  - PURPOSE: A new form of aberrometry based on Tscherning optics has been proposed
      that captures the refraction and high-order aberrations of the eye with and
      without accommodation. DESIGN: Experimental clinical optics study. METHOD: A
      green neodymium:yttrium-aluminum-garnet laser grid pattern is projected into the
      eye and viewed on the retina through a narrow, collimated aperture of 1 mm. The
      resulting aberrated pattern is photographically recorded in a normal eye in the
      unaccommodated and accommodated state through a pharmacologically dilated pupil
      without cycloplegia. MAIN OUTCOME MEASURES: Detection of pupil-dependent
      refraction and high-order optical aberration with and without accommodation.
      RESULTS: Subtle pupil-dependent errors in refraction and high-order aberrations
      (spherical aberrations and coma) are demonstrated in the unaccommodated normal
      eye. Accommodation reveals slightly more spherical power through the central 3-mm
      zone than through a 6.5-mm pupil without significant increase in aberration.
      CONCLUSIONS: Tscherning aberrometry based on 'retinal imaging' is useful in
      defining the refraction and optical aberrations in a normal eye. Accommodation
      increases spherical refractive power with only small aberration changes,
      including negative asphericity.

PMID- 11297483
TI  - A population-based eye survey of older adults in a rural district of Rajasthan:
      I. Central vision impairment, blindness, and cataract surgery.
AB  - PURPOSE: To assess the prevalence of central vision blindness and cataract
      surgery in older adults in rural northwest India. DESIGN: Population-based, cross
      sectional study. PARTICIPANTS: A total of 4284 examined persons 50 years of age
      or older. METHODS: A random selection of village-based clusters was used to
      identify a population sample in the predominantly rural Bharatpur district of
      Rajasthan. Eligible subjects in the 25 selected clusters were enumerated through
      a door-to-door household survey and invited to village sites for visual acuity
      testing and eye examination early in 1999. The principal cause of reduced central
      vision was identified for eyes that had visual acuity worse than 6/18.
      Independent replicate testing for quality assurance monitoring took place in
      participants with reduced vision and in a sample of those with normal vision in
      five of the study clusters. MAIN OUTCOME MEASURES: Presenting and best-corrected
      visual acuity and lens status. RESULTS: A total of 4728 eligible persons in 2821
      households were enumerated, and 4284 (90.6%) were examined. The prevalence of
      presenting and best-corrected visual acuity worse than 6/60 in both eyes was
      11.9% (95% confidence interval: 10.0%-13.9%) and 6.1% (95% CI: 4.7%-7.4%),
      respectively. Presenting blindness was associated with increasing age, female
      gender, lack of schooling, and rural residence. Cataract was the principal cause
      of blindness in one or both eyes in 67.5% of blind persons, with uncorrected
      aphakia and other refractive error affecting 18.4% in at least one eye. The
      prevalence of cataract surgery was 12.8% (95% CI: 11.6%-14.0%), with an estimated
      65.7% of the cataract blind operated on; low surgical coverage was associated
      with lack of schooling. CONCLUSIONS: Blindness, particularly blindness because of
      cataract, continues to be a significant problem among the elderly living in
      remote areas of rural northwest India. Increased attention should be given to
      reaching women and the illiterate.

PMID- 11297484
TI  - A population-based eye survey of older adults in a rural district of Rajasthan:
      II. Outcomes of cataract surgery.
AB  - PURPOSE: To assess the outcomes of cataract surgery in rural northwest India.
      DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 549
      cataract-operated persons (723 operated eyes). METHODS: Cluster sampling was used
      in randomly selecting a cross-sectional sample of persons 50 years of age or
      older for visual acuity measurement, refraction, and slit-lamp and direct
      ophthalmoscope examination early in 1999. Those operated on for cataract were
      queried as to the date and place of surgery. The principal cause of reduced
      vision was identified for all examined eyes with presenting visual acuity worse
      than 6/18. MAIN OUTCOME MEASURES: Presenting and best-corrected visual acuity and
      cause of vision loss. RESULTS: Presenting visual acuity was less than 6/60 in the
      better eye in 33.7% of cataract-operated persons and greater than or equal to
      6/18 in both eyes in 8.2%; 31.7% were bilaterally operated on. Of cataract
      operated eyes, 44.1% initially had visual acuity less than 6/60 and 31.5% greater
      than or equal to 6/18; with best correction, the corresponding percentages were
      14.0% and 61.5%. Intracapsular cataract extraction was used in 92% of cases, and
      66% had been operated on in surgery camps. Surgical complications were common and
      a major cause of vision impairment. In multiple logistic regression modeling,
      female gender and residence in a rural area were associated negatively with both
      presenting and best-corrected visual acuity outcomes, and surgery conducted
      before 1990 was associated negatively with best-corrected visual acuity. Place of
      surgery and subject schooling were not associated with vision outcomes.
      CONCLUSIONS: Cataract surgery subjects in rural areas of India that are without
      adequately equipped facilities and skilled surgeons, and lack of availability of
      intraocular lenses, are not realizing the full sight-restoring potential of
      modern-day surgery. Emphasis on the quality of cataract surgery outcomes must be
      increased to keep pace with that being given to increasing surgical volume.

PMID- 11297485
TI  - Etiology of blindness in an urban community hospital setting.
AB  - OBJECTIVE: To determine the cause of monocular and binocular blindness in a
      predominantly nonwhite urban community hospital setting. DESIGN: Retrospective
      hospital-based cross-sectional study. PARTICIPANTS: All 3562 unique subjects
      examined in the New and General Ophthalmology clinic at Parkland Memorial
      Hospital, Dallas, Texas, from July 1 to September 30, 1998. METHODS: The
      EYEstation program by Datamedic was queried to conduct a detailed review of
      electronic medical records of the participants listed previously. MAIN OUTCOME
      MEASURES: Blindness was defined as visual acuity </=20/200 in at least one eye.
      Records of blind subjects were subjected to further review. RESULTS: Of the 3562
      subjects examined, 321 (9.0%) were blind in one eye and 76 (2.1%) were blind in
      both eyes. Retinal disease was the leading cause of blindness (90 = 22.7%), with
      retinal vascular occlusions and retinal detachments accounting for more than half
      of retinal causes. Trauma (71 = 17.9%), diabetes (68 = 17.1%), and glaucoma (62 =
      15.6%) were the next most frequent causes. Trauma was the leading cause of
      blindness among subjects less than 40 years old and among blind new subjects. The
      most common cause of blindness among the 40- to 59-year-old age group was
      diabetes, accounting for 26.1% of cases. Age-related macular degeneration
      accounted for only 1.3% (n = 5) of blindness. CONCLUSIONS: Retinal diseases,
      especially retinal vascular occlusions and retinal detachments, are leading
      causes of blindness in this predominantly nonwhite and uninsured subject
      population. Trauma is a significant cause of severe, unilateral vision loss,
      especially in the young and in newly presenting subjects. Diabetes was the
      leading cause of blindness among the 40- to 59-year-old population. Age-related
      macular degeneration plays a relatively minor role in the cause of blindness in
      the study population.

PMID- 11297486
TI  - Risk factors for age-related macular degeneration: Pooled findings from three
      continents.
AB  - OBJECTIVE: To assess the prevalence and potential risk factors for late age
      related macular degeneration (AMD) in three racially similar populations from
      North America, Europe, and AUSTRALIA: DESIGN: Combined analysis of population
      based eye disease prevalence data. PARTICIPANTS: There were 14,752 participants
      with gradable photographs from the Beaver Dam Eye Study (n = 4756), Rotterdam
      Study (n = 6411), and Blue Mountains Eye Study (n = 3585). MAIN OUTCOME MEASURES:
      AMD diagnosis was made from masked grading of stereo macular photographs. Final
      classification of AMD cases was agreed by consensus between study investigators.
      RESULTS: AMD prevalence was strongly age related. Overall, AMD was present in
      0.2% of the combined population aged 55 to 64 years, rising to 13% of the
      population older than 85 years. Prevalence of neovascular AMD (NV) increased from
      0.17% among subjects aged 55 to 64 years to 5.8% for those older than 85 years.
      Prevalence of pure geographic atrophy (GA) increased from 0.04% to 4.2% for these
      age groups. There were no significant gender differences in the prevalence of NV
      or GA. Subjects in the Rotterdam population had a significantly lower age
      adjusted and smoking-adjusted risk of NV than subjects in the Beaver Dam and Blue
      Mountains populations. Apart from age, tobacco smoking was the only risk factor
      consistently associated with any form of AMD in all sites separately and in
      pooled analyses over the three sites. CONCLUSIONS: These combined data from
      racially similar communities across three continents provide strong and
      consistent evidence that tobacco smoking is the principal known preventable
      exposure associated with any form of AMD.

PMID- 11297487
TI  - Age-related macular degeneration is associated with increased vascular
      endothelial growth factor, hemorheology and endothelial dysfunction.
AB  - OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis,
      hemorheologic factors, endothelial damage/dysfunction, and age-related macular
      degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We
      studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation
      [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were
      compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND
      OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of
      angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell
      count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis),
      and von Willebrand factor (a marker of endothelial dysfunction) were measured.
      RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von
      Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects
      than the controls. Mean plasma fibrinogen and plasma viscosity levels were also
      higher in the subjects (both P < 0.0001). There were no significant differences
      in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28)
      and "exudative" (n = 50) ARMD subjects were compared, there was no significant
      differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels.
      There were no significant correlations between the measured parameters. Stepwise
      multiple regression analysis did not demonstrate any significant clinical
      predictors (age, gender, smoking, body mass index, history of vascular disease,
      or hypertension) for plasma VEGF or fibrinogen levels, although smoking status
      was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS:
      This study suggests an association between markers of angiogenesis (VEGF),
      hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The
      interaction between abnormal angiogenesis and the components of Virchow's triad
      for thrombogenesis may in part contribute to the pathogenesis of ARMD.

PMID- 11297488
TI  - Evaluation of retinal photoreceptors and pigment epithelium in a female carrier
      of choroideremia.
AB  - PURPOSE: To clarify the pathogenesis of choroideremia. STUDY DESIGN: Human tissue
      study. TISSUES: Eyes of an 88-year-old symptomatic female carrier of
      choroideremia (CHM) and six normal, age-matched donors. METHODS: The eyes were
      processed for histopathologic examination, including immunocytochemistry with an
      antibody against the CHM gene product, REP-1, and retinal cell-specific markers.
      RESULTS: The CHM carrier retina showed patchy degeneration, but the photoreceptor
      and retinal pigment epithelium (RPE) loss appeared to be independent. The
      choriocapillaris was normal except where retinal areas were severely degenerate.
      The CHM gene product, REP-1, was localized to the cytoplasm of rods but not
      cones. CONCLUSIONS: It has generally been considered that photoreceptor
      degeneration in CHM is secondary to loss of the choriocapillaris or RPE. This
      study suggests that the rod photoreceptors are a primary site of disease in CHM.

PMID- 11297489
TI  - Ophthalmologic heterogeneity in subjects with gyrate atrophy of choroid and
      retina harboring the L402P mutation of ornithine aminotransferase.
AB  - OBJECTIVE/PURPOSE: To investigate clinical variation in a genetically homogenous
      group of subjects with gyrate atrophy of choroid and retina with
      hyperornithinemia (GA). The group was made up of homozygotes and compound
      heterozygotes for mutation L402P in the ornithine aminotransferase (OAT) gene.
      DESIGN: Cross-sectional study. PARTICIPANTS: Thirty-five Finnish subjects (18
      men) with GA with a mean age of 33 years (range, 5-74 years) carrying the Finnish
      founder mutation L402P. METHODS: All subjects were examined between 1993 and
      1995. The analysis was composed of, in addition to careful clinical evaluation,
      studies of visual fields with Goldmann perimeter, photographing of the eye fundi,
      and corneal electroretinography (ERG) recordings. MAIN OUTCOME MEASURES: The
      changes in eye fundi, visual acuity, cataract changes in the lens, visual field
      constriction, and ERG responses were determined. RESULTS: Myopia, early
      cataracts, and highly abnormal ERG were typical for the GA subjects. The changes
      progressed rather uniformly with age. However, visual acuity, funduscopic
      findings, and visual fields showed great phenotypic variation. Despite the great
      interindividual variation, both eyes of each subject were always similarly
      affected. CONCLUSIONS: This study of 35 subjects with GA carrying a single
      mutation shows that the ophthalmologic symptoms and findings vary widely. The
      data also reveal that GA subjects are already affected by severe visual
      impairment in young adulthood. However, the diagnosis is often made very late.

PMID- 11297490
TI  - Macular pigment optical density in a midwestern sample.
AB  - OBJECTIVE: To assess the distribution of the macular pigments (MPs) lutein (L)
      and zeaxanthin (Z) in a healthy sample more representative of the general
      population than past studies and to determine which dietary factors and personal
      characteristics might explain the large interindividual differences in the
      density of these MPs. DESIGN: Prevalence study in a self-selected population.
      PARTICIPANTS: Two hundred eighty healthy adult volunteers, consisting of 138 men
      and 142 women, between the ages of 18 and 50 years, recruited from the general
      population. METHODS: MP optical density was measured psychophysically at 460 nm
      by use of a 1 degrees test field. Serum was analyzed for carotenoid and vitamin E
      content with reversed-phase high-performance liquid chromatography. Usual intakes
      of nutrients over the past year were determined by means of a food frequency
      questionnaire. MAIN OUTCOME MEASURES: MP optical density. RESULTS: Mean MP
      optical density measured 0.211 +/- 0.13, which is approximately 40% lower than
      the average reported in smaller, less representative studies. MP density was 44%
      lower in the bottom versus the top quintile of serum L and Z concentrations.
      Similarly, MP density was 33% lower in the bottom compared with the top quintile
      of L and Z intake. MP density was 19% lower in blue-grey-eyed subjects than in
      subjects with brown-black irises. When all variables were considered together in
      a general linear model of determinants of MP, statistically significant (P <
      0.05) relationships were found between MP density and serum L and Z, dietary L
      and Z intake, fiber intake, and iris color. CONCLUSIONS: These data suggest that
      MP values in this healthy adult population are lower than in smaller select
      samples. Moreover, these data indicate that MP is related to serum L and Z,
      dietary L and Z intake, fiber intake, and iris color.

PMID- 11297491
TI  - Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal
      morbidity.
AB  - PURPOSE: To report ocular and renal findings specific to the inheritable entity
      called papillorenal (also known as renal-coloboma) syndrome and relate these to a
      common cause. DESIGN: Observational case series and genetic study. PARTICIPANTS:
      Two unrelated probands presenting with absent central retinal vessels and 11
      available family members. TESTING: Doppler ultrasonographic imaging of the optic
      nerves and kidneys, fluorescein angiography, and genetic testing for PAX2
      mutations were performed. In selected cases, indocyanine green angiography,
      scanning laser ophthalmoscope perimetry, Retinal Thickness Analyzer measurements,
      visual evoked potentials, and magnetic resonance imaging were also performed.
      MAIN OUTCOME MEASURES: Better defined characteristics of the papillorenal
      syndrome. RESULTS: Numerous cilioretinal vessels were present with rudimentary or
      absent central retinal vessels. Superonasal visual field defects, typical for
      papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal
      and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered
      in two affected members of one family (with previously unsuspected renal failure
      in one case), and recurrent pyelonephritis was discovered in four affected
      members of the other family. No PAX2 mutations were detected. CONCLUSIONS: In the
      papillorenal syndrome, the hereditary absence of central retinal vessels may be
      missed, leading to confusion with isolated coloboma, low-tension glaucoma, and
      morning glory anomaly. Greater awareness of this syndrome will avoid unneeded
      glaucoma therapy, allow earlier recognition of renal diseases, and allow genetic
      counseling. We propose that the papillorenal syndrome is a primary dysgenesis
      that causes vascular abnormalities predominantly affecting the eye, kidney, and
      urinary tract, leading to hypoplasia of these structures. The absence of defects
      in the PAX2 gene in these families suggests that mutations in other genes may
      also be responsible for this syndrome.

PMID- 11297492
TI  - Rifabutin-associated hypopyon uveitis in human immunodeficiency virus-negative
      immunocompetent individuals.
AB  - OBJECTIVE: To report the occurrence of rifabutin-associated hypopyon uveitis in
      human immunodeficiency virus (HIV)-negative immunocompetent individuals. DESIGN:
      Retrospective case series. PARTICIPANTS: Three HIV-negative subjects on rifabutin
      and clarithromycin for Mycobacterium avium complex infections with hypopyon
      uveitis are described. One subject was iatrogenically immunosuppressed because of
      a prior lung transplant. Two subjects had no known immunosuppressive conditions.
      INTERVENTION: Topical and regional steroid therapy. Discontinuation of rifabutin
      was required in two subjects. MAIN OUTCOME MEASURES: Visual acuity, resolution of
      hypopyon, anterior uveitis, and vitreitis. RESULTS: All subjects had resolution
      of hypopyon after therapy, two within 24 hours of beginning topical steroids.
      Vitreitis resolved with the discontinuation of rifabutin in two subjects. Chronic
      low-grade anterior uveitis and vitreitis were observed in the remaining subject,
      whose rifabutin dose was lowered but not discontinued because of active
      Mycobacterium avium complex osteomyelitis. CONCLUSIONS: Rifabutin-associated
      uveitis is well described in HIV-positive individuals, but it has been reported
      only once in an HIV-negative individual. We report two cases of hypopyon uveitis
      in immunocompetent individuals and one case in an immunosuppressed HIV-negative
      individual. All three subjects were receiving concurrent rifabutin and
      clarithromycin. Awareness that this entity can occur in HIV negative and
      nonimmunosuppressed individuals and that it can mimic infectious endophthalmitis
      may spare the subject from an invasive workup of systemic infection.

PMID- 11297493
TI  - Rescue of exposed scleral buckles with cadaveric pericardial patch grafts.
AB  - PURPOSE: To describe a new method for salvaging externally exposed silicone
      scleral exoplants (buckles) to avoid removal and the consequent risk of retinal
      redetachment. DESIGN: A retrospective, noncomparative, interventional case
      series. PARTICIPANTS: Four patients with exposed, clinically uninfected scleral
      buckles after initial surgery for the treatment of rhegmatogenous retinal
      detachment. INTERVENTION: Processed human donor pericardium patch grafts
      (Tutoplast; Innovative Ophthalmic Products, INC:, Costa Mesa, CA) were used to
      cover exposed areas of scleral buckles in concert with conjunctivoplasty. MAIN
      OUTCOME MEASURES: Scleral buckle preservation was the goal of this new treatment
      strategy. RESULTS: In four eyes treated with pericardial patch grafts to cover
      segments of exposed scleral buckles, three (75%) were managed successfully with
      one surgery. One eye (25%) had this treatment method fail and required scleral
      buckle removal. CONCLUSIONS: Processed human donor pericardium patch grafting is
      one useful way to avoid removing exposed scleral buckles, and consequently,
      sparing patients the risk of recurrent retinal detachment.

PMID- 11297494
TI  - Retinal toxicity of gentamicin after subconjunctival injection performed adjacent
      to thinned sclera.
AB  - OBJECTIVE: To investigate the potential toxicity to the retina of gentamicin
      injected near surgically thinned scleral areas in a rabbit model. DESIGN:
      Experimental study. METHODS: Scleral scraping to half thickness was performed in
      the superotemporal scleral area in both eyes of adult rabbits (n = 10).
      Gentamicin sulfate was injected subconjunctivally to the right eye and saline to
      the left eye, which always served as a control eye. Four weeks after the
      procedure, electroretinography (ERG) was performed to assess retinal function.
      Then, the eyes were enucleated and prepared for histologic evaluation of
      structural damage. In four eyes of two additional rabbits, vitreous gentamicin
      concentrations were measured using a fluorescence polarization assay. MAIN
      OUTCOME MEASURES: Dark- and light-adapted ERG responses and histopathologic
      damage. RESULTS: Dark- and light-adapted ERG responses in all rabbits were
      similar in the experimental and control eyes. Gentamicin levels were more than 10
      microg/ml after subconjunctival injection of gentamicin with scraping and 0.29
      microg/ml after subconjunctival injection of gentamicin with no scraping.
      Histopathologic examination revealed significant local damage to the
      photoreceptors adjacent to the area of scraping and subconjunctival injection. A
      significantly lesser degree of damage was seen if gentamicin was injected in
      pigmented rabbits or in albino rabbits, but only 4 weeks after scleral scraping.
      CONCLUSIONS: Increased penetration of gentamicin through thinned sclera may lead
      to toxic levels of the drug in a localized area adjacent to the site of
      injection. These toxic effects are also influenced by the degree of pigmentation
      and acute inflammation.

PMID- 11297495
TI  - Intravitreal triamcinolone for uveitic cystoid macular edema: an optical
      coherence tomography study.
AB  - PURPOSE: To investigate the use of intravitreal injection of triamcinolone
      acetonide (TA) for the treatment of refractory uveitic cystoid macular edema
      (CME). DESIGN: Prospective, nonrandomized, self-controlled comparative trial.
      PARTICIPANTS: Six patients with chronic CME resistant to treatment with systemic
      steroids, orbital floor steroids, and cyclosporine A. Three patients were
      followed for more than 1 year, and the other three for between 3 and 9 months.
      INTERVENTION: Injection of 2 mg of TA into the vitreous cavity. TESTING: Optical
      coherence tomography scanning of the fovea before and after injection and
      logarithmic minimal angle of resolution visual acuity. MAIN OUTCOME MEASURES:
      Visual acuity, retinal thickness, cystoid space height, and intraocular pressure.
      RESULTS: There was complete anatomic resolution of CME in five of the six cases
      within 1 week after injection. Cystoid spaces began to return between 6 weeks and
      3 months after injection. Two patients with longer term follow-up responded to
      further orbital floor steroid injection and had no CME 1 year later. One patient
      had raised intraocular pressure develop, requiring a trabeculectomy. Mean
      improvement in visual acuity after 12 months was 0.27 (range, 0.14-0.42).
      CONCLUSIONS: Complete anatomic and, to some extent, functional recovery can be
      induced by intravitreal TA despite long-term refractory inflammatory CME. Optical
      coherence tomography aids in the management of these cases.

PMID- 11297496
TI  - Comparison of the morphologic changes after selective laser trabeculoplasty and
      argon laser trabeculoplasty in human eye bank eyes.
AB  - OBJECTIVE: To compare the histopathologic changes in the human trabecular
      meshwork (TM) after argon laser trabeculoplasty (ALT) and selective laser
      trabeculoplasty (SLT) with a Q-switched, frequency-doubled, neodymium:yttrium
      aluminum-garnet laser. DESIGN: Human "in vitro" experimental study. TISSUE AND
      CONTROLS: Eight human autopsy eyes were obtained within 18 hours of death from
      persons aged 71 to 78 years. METHODS: The anterior segment of autopsy eyes was
      isolated, and one half of each trabecular meshwork underwent SLT and the other
      half ALT. Specimens were evaluated with scanning and transmission electron
      microscopy. MAIN OUTCOME MEASURES: Structural changes in the TM were detected by
      scanning electron microscopy, and cellular or intracellular changes were seen
      with transmission electron microscopy. RESULTS: Evaluation of the TM after ALT
      revealed crater formation in the uveal meshwork at the junction of the pigmented
      and nonpigmented TM. Coagulative damage was evident at the base and along the
      edge of craters, with disruption of the collagen beams, fibrinous exudate, lysis
      of endothelial cells, and nuclear and cytoplasmic debris. Evaluation of the TM
      after SLT revealed no evidence of coagulative damage or disruption of the
      corneoscleral or uveal trabecular beam structure. Minimal evidence of mechanical
      damage was present after SLT, and the only ultrastructural evidence of laser
      tissue interaction was cracking of intracytoplasmic pigment granules and
      disruption of trabecular endothelial cells. CONCLUSIONS: SLT applied "in vitro"
      to the TM of human eye bank eyes seemed to cause no coagulative damage and less
      structural damage to the human TM when compared with ALT and, therefore, may be a
      safer and more repeatable procedure.

PMID- 11297497
TI  - New surgical approach in the management of pseudophakic malignant glaucoma.
AB  - PURPOSE: To describe a new surgical approach in the management of pseudophakic
      malignant glaucoma. DESIGN: Noncomparative case series. PARTICIPANTS: Five
      consecutive patients with pseudophakic malignant glaucoma. METHODS: All patients
      underwent zonulo-hyaloido-vitrectomy. The procedure involves the performance of
      zonulectomy, hyaloidectomy, and anterior vitrectomy (zonulo-hyaloido-vitrectomy)
      through a peripheral iridectomy or iridotomy via the anterior chamber. MAIN
      OUTCOME MEASURES: Medications, visual acuity, intraocular pressure, and anterior
      and posterior segment findings were recorded before and after surgery. RESULTS:
      Resolution of the malignant glaucoma was achieved in all cases. No recurrences
      were observed after a median follow-up of 5.5 months (range, 1-9 months). In one
      patient with extensive anterior synechiae, bleb failure occurred after the
      resolution of the malignant glaucoma. This patient was treated successfully with
      a guarded filtration procedure supplemented with 5-fluorouracil. No other
      complications were observed. CONCLUSIONS: Zonulo-hyaloido-vitrectomy via the
      anterior segment appears to be an alternative option in the treatment of patients
      with pseudophakic malignant glaucoma.

PMID- 11297498
TI  - Vitreous concentration of topically applied brimonidine tartrate 0.2%.
AB  - OBJECTIVE: To determine the vitreous concentration of brimonidine after topical
      administration of Alphagan. DESIGN: Prospective observational case series.
      PARTICIPANTS: Eighteen patients scheduled for elective pars plana vitrectomy.
      METHODS: Brimonidine tartrate, 0.2%, was topically administered twice or three
      times daily for 4 to 14 days preoperatively in 13 patients. Four patients served
      as controls, without application of brimonidine. A dry, undiluted vitrectomy
      specimen obtained intraoperatively was collected, frozen, and sent to an
      independent bioanalytical facility for quantitative determination of vitreous
      concentration of brimonidine using gas chromatography/mass spectrometry. MAIN
      OUTCOME MEASURES: The concentration of brimonidine in human vitreous. RESULTS:
      All patients treated with brimonidine measured above the lower limit of
      quantitation with a mean vitreous concentration of 185 +/- 500 nM. All patients
      not treated with brimonidine measured at or below the lower limit of quantitation
      of 0.05 nM. There was a trend toward higher concentration in patients who were
      either aphakic or pseudophakic compared with those that were phakic. CONCLUSIONS:
      Topically applied brimonidine results in vitreous levels at or above 2 nM, the
      concentration shown to activate alpha(2)-receptors.

PMID- 11297499
TI  - Bungee cord-associated ocular trauma.
AB  - PURPOSE: To discuss the incidence and to characterize the clinical features of
      ocular trauma associated with bungee cord injuries. DESIGN: Retrospective case
      series. PARTICIPANTS: The authors identified 67 subjects (60 males) treated at
      Wills Eye Hospital for ocular trauma resulting from bungee cords between
      September 1, 1994, and September 1, 1999. METHODS: The authors reviewed subjects'
      records from Wills Eye Hospital, records from outside physicians involved in the
      subjects' care, and conducted telephone interviews when additional information
      was needed. MAIN OUTCOME MEASURES: Each chart was reviewed for demographic
      information, mechanism of injury, presenting visual acuity, anterior segment,
      posterior segment and periocular injuries, medical and surgical intervention,
      final visual acuity, and length of follow-up. RESULTS: Mean visual acuity on
      presentation was 20/150. The most common anterior, posterior, and periocular
      injuries were hyphema (42/67, 63%), commotio retinae (30/55, 55%), and eyelid
      edema/ecchymosis (40/67, 60%), respectively. Seven subjects (10%) sustained open
      globe injuries, three (4%) of whom required enucleation. Eighteen subjects (27%)
      required medical treatment, and 4 subjects (6%) required surgical treatment for
      increased intraocular pressure. A total of 21 subjects (31%) required some form
      of surgical intervention. Mean final visual acuity was 20/60, with an average
      follow-up of 34 weeks. CONCLUSIONS: This series, the largest to date,
      demonstrates a wide spectrum of serious ocular injuries related to bungee cord
      use. Medical and surgical treatments are commonly necessary to manage these
      injuries. We advocate a modification in the design of these cords and appropriate
      printed warnings directed to the users of bungee cords regarding the potential
      for severe ocular trauma.

PMID- 11297500
TI  - Partial lacrimal carunculectomy: a simple procedure for epiphora.
AB  - OBJECTIVE: To evaluate the effect of partial surgical excision of enlarged
      lacrimal caruncles, termed megalocaruncles, in patients with epiphora from
      functional lacrimal drainage obstruction. DESIGN: Retrospective, noncomparative,
      interventional case series. PARTICIPANTS: From May 1995 through December 1999, 88
      patients (46 women and 42 men; mean age, 68 years) with epiphora, patent lacrimal
      drainage system on irrigation, and a megalocaruncle underwent a partial lacrimal
      carunculectomy procedure. In 26 patients, a bilateral partial lacrimal
      carunculectomy was performed. INTERVENTION: Lacrimal caruncular tissue, with its
      overlying mucosa, was partially excised, and the wound was closed with
      interrupted sutures. MAIN OUTCOME MEASURES: Symptomatology and patient
      satisfaction. RESULTS: After a partial lacrimal carunculectomy procedure,
      epiphora was subjectively improved in 77% of the patients, ranging from complete
      relief in 33% to significant improvement in 44% of the patients. Twenty-three
      percent of the patients had no change in symptoms. The mean follow-up was 12.7
      months. CONCLUSIONS: Megalocaruncles can be the cause of epiphora in patients
      with functional lacrimal drainage obstruction, for whom a partial lacrimal
      carunculectomy is an effective surgical procedure in 77% of the cases.

PMID- 11297502
TI  - Common forms of childhood esotropia.
AB  - OBJECTIVE: To determine the most common forms of childhood esotropia. DESIGN:
      Prospective, consecutive, observational case series. PARTICIPANTS: All esotropic
      children younger than 11 years of age from a predominantly rural Appalachian
      region evaluated from August 1, 1995 through July 31, 1998. METHODS: Demographic
      and clinical data were collected for all patients. MAIN OUTCOME MEASURES: The
      percentage ratio of the various forms of childhood esotropia. RESULTS: Two
      hundred twenty-one consecutive children without prior surgical treatment were
      evaluated for esotropia. One hundred seventeen (52.9%) of the 221 children had
      some form of accommodative esotropia, 38 (17.2%) were associated with congenital
      or acquired abnormalities of the central nervous system, 23 (10.4%) displayed
      acquired nonaccommodative esotropia, 15 (6.8%) resulted from ocular sensory
      defects, 12 (5.4%) had confirmed congenital esotropia, seven (3.2%) had paralytic
      esotropia, and an unverified age at onset prevented an accurate categorization in
      the remaining nine (4.1%). CONCLUSIONS: Children with accommodative esotropia
      accounted for more than half of the study patients and were diagnosed nearly 10
      times more frequently than children with congenital esotropia. Esotropic patients
      with central nervous system defects or with an acquired nonaccommodative
      deviation were also more common than children with congenital esotropia. Children
      with congenital esotropia or with a paralytic or sensory cause of their deviation
      were relatively uncommon.

PMID- 11297501
TI  - Rhabdomyomatous mesenchymal hamartoma of the eyelid: report of a case and
      literature review.
AB  - PURPOSE: To report a rare case of rhabdomyomatous mesenchymal hamartoma and to
      compare its features with those cases previously reported. DESIGN: Interventional
      case report and literature review. INTERVENTION: Complete ophthalmologic and
      systemic examinations followed by excisional biopsy and histopathologic
      examination. MAIN OUTCOME MEASURES: Clinical examination features and
      histopathologic findings. RESULTS: A 6-month-old Latino male presented with a
      congenital, elevated, smooth, flesh-colored right lower eyelid lesion. An
      ipsilateral right limbal dermoid and an upper eyelid coloboma were also present.
      Excisional biopsy of the eyelid lesion revealed randomly oriented mature striated
      muscle tissue with associated adipose tissue, blood vessels, pilosebaceous units,
      and peripheral nerves, findings consistent with rhabdomyomatous mesenchymal
      hamartoma. Of the 24 reported cases (including the current case), eight had
      associated congenital anomalies. CONCLUSIONS: Although rhabdomyomatous
      mesenchymal hamartomas are rare and benign, they may be associated with other
      congenital anomalies and anomaly syndromes. As a result, we recommend systemic
      evaluation of patients diagnosed with this entity.

PMID- 11297503
TI  - Alteration of the ocular surface with recurrence of granular/avellino corneal
      dystrophy after phototherapeutic keratectomy: report of five cases and literature
      review.
AB  - PURPOSE: To study the changes in ocular surface findings with recurrence after
      phototherapeutic keratectomy (PTK) in patients with Avellino and granular
      dystrophy. DESIGN: Observational case series. PARTICIPANTS: Five eyes of five
      patients with recurrent granular/Avellino corneal dystrophy after PTK seen at
      Kobe Kaisei Hospital were studied. INTERVENTION: The patients underwent routine
      ophthalmic examinations, corneal sensitivity measurements, tear film breakup time
      (BUT), Schirmer test, tear film lipid layer interferometry, and conjunctival
      impression cytology. MAIN OUTCOME MEASURES: The alterations of clinical features,
      tear function, and conjunctival impression cytology parameters with a recurrence
      after PTK were investigated. RESULTS: The average pre-PTK corneal sensitivity and
      tear film breakup time were low in all five patients. Tear film lipid layer
      interferometry grade and conjunctival squamous metaplasia displayed higher grades
      before PTK. All of these parameters improved gradually after PTK and were
      maintained until a recurrence, which was associated with further worsening of the
      corneal sensitivity, tear function, and impression cytology parameters.
      CONCLUSIONS: Although PTK improves the ocular surface health in granular/Avellino
      corneal dystrophies, recurrence of the initial dystrophy is associated with
      decline of the ocular surface health parameters. Our findings also suggest that
      corneal epithelium is most probably involved in the recurrence of the disease
      process in Avellino/granular corneal dystrophy.

PMID- 11297504
TI  - Histologic phenotype-genotype correlation of corneal dystrophies associated with
      eight distinct mutations in the TGFBI gene.
AB  - PURPOSE: To establish a phenotype-genotype correlation of various autosomal
      dominant corneal dystrophies among French subjects. DESIGN: Retrospective
      molecular genetic study and clinicopathologic correlation. PARTICIPANTS: Forty
      four subjects from 26 unrelated French families were included in this study, and
      60 corneal buttons could be examined at the histologic and ultrastructural
      levels. METHODS: Light microscopy and transmission electron microscopy were
      performed on corneal specimens obtained during keratoplasty. Blood samples were
      collected for DNA analysis. MAIN OUTCOME MEASURES: After genomic DNA extraction
      from peripheral blood leukocytes of each family member, exons of the TGFBI gene
      were amplified by polymerase chain reaction (PCR), and the PCR products were
      directly sequenced on both strands. RESULTS: Four different mutations were found
      to be responsible for dystrophy of granular type (R555W, R124L, R124H, and
      R124L+delT125-delE126), three other different mutations produced a lattice type
      (R124C, H626R, and A546T), and the last mutation identified was associated with
      the honeycomb-shaped dystrophy (R555Q). Each subtype of dystrophy showed,
      histologically and ultrastructurally, specific characteristics that are easily
      recognizable. However, besides these stereotyped forms, differential histologic
      diagnosis of atypical forms remains difficult, and these forms could be
      misdiagnosed. CONCLUSIONS: The characteristic biomicroscopic appearance and
      histopathologic features of each "classic" dystrophy present a significant degree
      of specificity and generally provide an accurate diagnosis. However, atypical
      forms in which clinical and histologic data alone could be misleading, are
      unequivocally diagnosed after DNA analysis.

PMID- 11297505
TI  - Regulation of translation initiation by FRAP/mTOR.

PMID- 11297506
TI  - The MeCP1 complex represses transcription through preferential binding,
      remodeling, and deacetylating methylated nucleosomes.
AB  - Histone deacetylation plays an important role in methylated DNA silencing. Recent
      studies indicated that the methyl-CpG-binding protein, MBD2, is a component of
      the MeCP1 histone deacetylase complex. Interestingly, MBD2 is able to recruit the
      nucleosome remodeling and histone deacetylase, NuRD, to methylated DNA in vitro.
      To understand the relationship between the MeCP1 complex and the NuRD complex, we
      purified the MeCP1 complex to homogeneity and found that it contains 10 major
      polypeptides including MBD2 and all of the known NuRD components. Functional
      analysis of the purified MeCP1 complex revealed that it preferentially binds,
      remodels, and deacetylates methylated nucleosomes. Thus, our study defines the
      MeCP1 complex, and provides biochemical evidence linking nucleosome remodeling
      and histone deacetylation to methylated gene silencing.

PMID- 11297507
TI  - Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of
      orphan nuclear receptor ERR beta.
AB  - The orphan nuclear receptor ERR beta is expressed in undifferentiated trophoblast
      stem cell lines and extraembryonic ectoderm, and genetic ablation of ERR beta
      results in abnormal trophoblast proliferation and precocious differentiation
      toward the giant cell lineage. Here, we show that the synthetic estrogen
      diethylstilbestrol (DES) promotes coactivator release from ERR beta and inhibits
      its transcriptional activity. Strikingly, treatment of trophoblast stem cells
      with DES led to their differentiation toward the polyploid giant cell lineage. In
      addition, DES-treated pregnant mice exhibited abnormal early placenta development
      associated with an overabundance of trophoblast giant cells and an absence of
      diploid trophoblast. These results define a novel pathway for DES action and
      provide evidence for steroidlike control of trophoblast development.

PMID- 11297508
TI  - Proper coronary vascular development and heart morphogenesis depend on
      interaction of GATA-4 with FOG cofactors.
AB  - GATA-family transcription factors are critical to the development of diverse
      tissues. In particular, GATA-4 has been implicated in formation of the vertebrate
      heart. As the mouse Gata-4 knock-out is early embryonic lethal because of a
      defect in ventral morphogenesis, the in vivo function of this factor in heart
      development remains unresolved. To search for a requirement for Gata4 in heart
      development, we created mice harboring a single amino acid replacement in GATA-4
      that impairs its physical interaction with its presumptive cardiac cofactor FOG
      2. Gata4(ki/ki) mice die just after embryonic day (E) 12.5 exhibiting features in
      common with Fog2(-/-) embryos as well as additional semilunar cardiac valve
      defects and a double-outlet right ventricle. These findings establish an
      intrinsic requirement for GATA-4 in heart development. We also infer that GATA-4
      function is dependent on interaction with FOG-2 and, very likely, an additional
      FOG protein for distinct aspects of heart formation.

PMID- 11297509
TI  - Nuclear translocation controlled by alternatively spliced isoforms inactivates
      the QUAKING apoptotic inducer.
AB  - The quaking viable mice have myelination defects and develop a characteristic
      tremor 10 d after birth. The quaking gene encodes at least five alternatively
      spliced QUAKING (QKI) isoforms that differ in their C-terminal 8--30-amino-acid
      sequence. The reason for the existence of the different QKI isoforms and their
      function are unknown. Here we show that only one QKI isoform, QKI-7, can induce
      apoptosis in fibroblasts and primary rat oligodendrocytes. Heterodimerization of
      the QKI isoforms results in the nuclear translocation of QKI-7 and the
      suppression of apoptosis. The unique C-terminal 14 amino acids of QKI-7 confers
      the ability to induce apoptosis to heterologous proteins such as the green
      fluorescent protein and a QKI-related protein, Caenorhabditis elegans GLD-1.
      Thus, the unique C-terminal sequences of QKI-7 may function as a life-or-death
      'sensor' that monitors the balance between the alternatively spliced QKI
      isoforms. Moreover, our findings suggest that nuclear translocation is a novel
      mechanism of inactivating apoptotic inducers.

PMID- 11297510
TI  - Ablation of NF1 function in neurons induces abnormal development of cerebral
      cortex and reactive gliosis in the brain.
AB  - Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects
      growth properties of neural-crest-derived cell populations. In addition,
      approximately one-half of NF1 patients exhibit learning disabilities. To
      characterize NF1 function both in vitro and in vivo, we circumvent the embryonic
      lethality of NF1 null mouse embryos by generating a conditional mutation in the
      NF1 gene using Cre/loxP technology. Introduction of a Synapsin I promoter driven
      Cre transgenic mouse strain into the conditional NF1 background has ablated NF1
      function in most differentiated neuronal populations. These mice have abnormal
      development of the cerebral cortex, which suggests that NF1 has an indispensable
      role in this aspect of CNS development. Furthermore, although they are tumor
      free, these mice display extensive astrogliosis in the absence of conspicuous
      neurodegeneration or microgliosis. These results indicate that NF1-deficient
      neurons are capable of inducing reactive astrogliosis via a non-cell autonomous
      mechanism.

PMID- 11297511
TI  - Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from
      recrossing, allowing for unilateral motor control.
AB  - Growing axons follow highly stereotypical pathways, guided by a variety of
      attractive and repulsive cues, before establishing specific connections with
      distant targets. A particularly well-known example that illustrates the
      complexity of axonal migration pathways involves the axonal projections of motor
      neurons located in the motor cortex. These projections take a complex route
      during which they first cross the midline, then form the corticospinal tract, and
      ultimately connect with motor neurons in the contralateral side of the spinal
      cord. These obligatory contralateral connections account for why one side of the
      brain controls movement on the opposing side of the body. The netrins and slits
      provide well-known midline signals that regulate axonal crossings at the midline.
      Herein we report that a member of the ephrin family, ephrin-B3, also plays a key
      role at the midline to regulate axonal crossing. In particular, we show that
      ephrin-B3 acts as the midline barrier that prevents corticospinal tract
      projections from recrossing when they enter the spinal gray matter. We report
      that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in
      the spinal gray matter, such that the motor cortex on one side of the brain now
      provides bilateral input to the spinal cord. This neuroanatomical abnormality in
      ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding
      mice that simultaneously move their right and left limbs and thus have a peculiar
      hopping gait quite unlike the alternate step gait displayed by normal mice. The
      corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently
      reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as
      other ephrins, suggesting that the binding of EphA4-bearing axonal processes to
      ephrin-B3 at the midline provides the repulsive signal that prevents
      corticospinal tract projections from recrossing the midline in the developing
      spinal cord.

PMID- 11297512
TI  - A developmental transition in definitive erythropoiesis: erythropoietin
      expression is sequentially regulated by retinoic acid receptors and HNF4.
AB  - The cytokine erythropoietin (Epo) promotes erythropoietic progenitor cell
      proliferation and is required for erythropoietic differentiation. We have found
      that the Epo gene is a direct transcriptional target gene of retinoic acid
      signaling during early erythropoiesis (prior to embryonic day E12.5) in the fetal
      liver. Mouse embryos lacking the retinoic acid receptor gene RXR alpha have a
      morphological and histological phenotype that is comparable with embryos in which
      the Epo gene itself has been mutated, and flow cytometric analysis indicates that
      RXR alpha-deficient embryos are deficient in erythroid differentiation. Epo mRNA
      levels are reduced substantially in the fetal livers of RXR alpha(-/-) embryos at
      E10.25 and E11.25, and genetic analysis shows that the RXR alpha and Epo genes
      are coupled in the same pathway. We furthermore show that the Epo gene is
      retinoic acid inducible in embryos, and that the Epo gene enhancer contains a DR2
      sequence that represents a retinoic acid receptor-binding site and a retinoic
      acid receptor transcriptional response element. However, unlike Epo-deficient
      embryos that die from anemia, the erythropoietic deficiency in RXR alpha(-/-)
      embryos is transient; Epo mRNA is expressed at normal levels by E12.5, and
      erythropoiesis and liver morphology are normal by E14.5. We show that HNF4, like
      RXR alpha a member of the nuclear receptor family, is abundantly expressed in
      fetal liver hepatocytes, and is competitive with retinoic acid receptors for
      occupancy of the Epo gene enhancer DR2 element. We propose that Epo expression is
      regulated during the E9.5--E11.5 phase of fetal liver erythropoiesis by RXR alpha
      and retinoic acid, and that expression then becomes dominated by HNF4 activity
      from E11.5 onward. This transition may be responsible for switching regulation of
      Epo expression from retinoic acid control to hypoxic control, as is found
      throughout the remainder of life.

PMID- 11297513
TI  - ABP1 is required for organized cell elongation and division in Arabidopsis
      embryogenesis.
AB  - To directly address the function of a putative auxin receptor designated ABP1, a
      reverse genetic approach was taken to identify and characterize ABP1 mutant
      alleles in Arabidopsis. A homozygous null mutation in ABP1 confers embryo
      lethality. Null mutant embryos develop normally until the early stages of the
      globular embryo but are unable to make the transition to a bilaterally
      symmetrical structure because cells fail to elongate. Cell division was also
      aberrant both in the suspensor and embryo proper. Antisense suppression of ABP1
      in tobacco cells causes slow proliferation and eliminates auxin-induced cell
      elongation and reduces cell division. The complete lack of auxin-inducible
      elongation in individual cells confirms the results observed in embryos,
      indicates a cell autonomous function, and, taken together with biochemical
      evidence that ABP1 binds auxins, suggests that ABP1 mediates auxin-induced cell
      elongation and, directly or indirectly, cell division.

PMID- 11297514
TI  - The Arabidopsis HOS1 gene negatively regulates cold signal transduction and
      encodes a RING finger protein that displays cold-regulated nucleo--cytoplasmic
      partitioning.
AB  - Low temperature is one of the most important environmental stimuli that control
      gene transcription programs and development in plants. In Arabidopsis thaliana,
      the HOS1 locus is a key negative regulator of low temperature-responsive gene
      transcription. The recessive hos1 mutation causes enhanced induction of the CBF
      transcription factors by low temperature as well as of their downstream cold
      responsive genes. The hos1 mutant plants flower early, and this correlates with a
      low level of Flowering Locus C gene expression. The HOS1 gene was isolated
      through positional cloning. HOS1 encodes a novel protein with a RING finger motif
      near the amino terminus. HOS1 is ubiquitously expressed in all plant tissues.
      HOS1--GFP translational fusion studies reveal that HOS1 protein resides in the
      cytoplasm at normal growth temperatures. However, in response to low temperature
      treatments, HOS1 accumulates in the nucleus. Ectopic expression of HOS1 in wild
      type plants causes cosuppression of HOS1 expression and mimics the hos1 mutant
      phenotypes.

PMID- 11297515
TI  - Substrate binding is the rate-limiting step in thromboxane synthase catalysis.
AB  - Thromboxane synthase (TXAS) is a "non-classical" cytochrome P450. Without any
      need for an external electron donor, or for a reductase or molecular oxygen, it
      uses prostaglandin H2 (PGH2) to catalyze either an isomerization reaction to form
      thromboxane A2 (TXA2) or a fragmentation reaction to form 12-l-hydroxy-5,8,10
      heptadecatrienoic acid and malondialdehyde (MDA) at a ratio of 1:1:1
      (TXA2:heptadecatrienoic acid:MDA). We report here kinetics of TXAS with heme
      ligands in binding study and with PGH2 in enzymatic study. We determined that 1)
      binding of U44069, an oxygen-based ligand, is a two-step process; U44069 first
      binds TXAS, then ligates the heme-iron with a maximal rate constant of 105-130 s(
      1); 2) binding of cyanide, a carbon-based ligand, is a one-step process with
      k(on) of 2.4 M(-1) s(-1) and k(off) of 0.112 s(-1); and 3) both imidazole and
      clotrimazole (nitrogen-based ligands) bind TXAS in a two-step process; an initial
      binding to the heme-iron with on-rate constants of 8.4 x 10(4) M(-1) s(-1) and
      1.5 x 10(5) M(-1) s(-1) for imidazole and clotrimazole, respectively, followed by
      a slow conformational change with off-rate constants of 8.8 s(-1) and 0.53 s(-1),
      respectively. The results of our binding study indicate that the TXAS active site
      is hydrophobic and spacious. In addition, steady-state kinetic study revealed
      that TXAS consumed PGH2 at a rate of 3,800 min(-1) and that the k(cat)/K(m) for
      PGH2 consumption was 3 x 10(6) M(-1) s(-1). Based on these data, TXAS appears to
      be a very efficient catalyst. Surprisingly, rapid-scan stopped-flow experiments
      revealed marginal absorbance changes upon mixing TXAS with PGH2, indicating
      minimal accumulation of any heme-derived intermediates. Freeze-quench EPR
      measurements for the same reaction showed minimal change of heme redox state.
      Further kinetic analysis using a combination of rapid-mixing chemical quench and
      computer simulation showed that the kinetic parameters of TXAS-catalyzed reaction
      are: PGH2 bound TXAS at a rate of 1.2-2.0 x 10(7) M(-1) s(-1); the rate of
      catalytic conversion of PGH2 to TXA2 or MDA was at least 15,000 s(-1) and the
      lower limit of the rates for products release was 4,000-6,000 s(-1). Given that
      the cellular PGH2 concentration is quite low, we concluded that under
      physiological conditions, the substrate-binding step is the rate-limiting step of
      the TXAS-catalyzed reaction, in sharp contrast with "classical" P450 enzymes.

PMID- 11297516
TI  - Its8, a fission yeast homolog of Mcd4 and Pig-n, is involved in GPI anchor
      synthesis and shares an essential function with calcineurin in cytokinesis.
AB  - In fission yeast, calcineurin is required for cytokinesis and ion homeostasis;
      however, most of its physiological roles remain obscure. To identify genes that
      share an essential function with calcineurin, we screened for mutations that
      confer sensitivity to the calcineurin inhibitor FK506 and high temperature and
      isolated the mutant its8-1. its8(+) encodes a homolog of the budding yeast MCD4
      and human Pig-n that are involved in glycosylphosphatidylinositol (GPI) anchor
      synthesis. Consistently, reduced inositol labeling of proteins suggested impaired
      GPI anchor synthesis in its8-1 mutants. The temperature upshift induced a further
      decrease in inositol labeling and caused dramatic increases in the frequency of
      septation in its8-1 mutants. BE49385A, an inhibitor of MCD4 and Pig-n, also
      increased the septation index of the wild-type cell. Osmotic stabilization
      suppressed these morphological defects, indicating that cell wall weakness caused
      by impaired GPI anchor synthesis resulted in abnormal cytokinesis. Furthermore,
      calcineurin-deleted cells exhibited hypersensitivity to BE49385A, and FK506
      exacerbated the cytokinesis defects of the its8-1 mutant. Thus, calcineurin and
      Its8 may share an essential function in cytokinesis and cell viability through
      the regulation of cell wall integrity.

PMID- 11297517
TI  - Regulation of macrophage migration inhibitory factor and thiol-specific
      antioxidant protein PAG by direct interaction.
AB  - Macrophage migration inhibitory factor (MIF) is an important mediator that plays
      a central role in the control of the host immune and inflammatory response. To
      investigate the molecular mechanism of MIF action, we have used the yeast two
      hybrid system and identified PAG, a thiol-specific antioxidant protein, as an
      interacting partner of MIF. Association of MIF with PAG was found in 293T cells
      transiently expressing MIF and PAG. The use of PAG mutants (C52S, C71S, and
      C173S) revealed that this association was significantly affected by C173S, but
      not C52S and C71S, indicating that a disulfide involving Cys(173) of PAG is
      responsible for the formation of MIF-PAG complex. In addition, the interaction
      was highly dependent on the reducing conditions such as dithiothreitol or beta
      mercaptoethanol but not in the presence of H2O2. Analysis of the activities of
      the interacting proteins showed that the D-dopachrome tautomerase activity of MIF
      was decreased in a dose-dependent manner by coexpression of wild-type PAG, C52S,
      and C71S, whereas C173S was almost ineffective, suggesting that the direct
      interaction may be involved in the control of D-dopachrome tautomerase activity
      of MIF. Moreover, MIF has been shown to bind to PAG and it also inhibits the
      antioxidant activity of PAG.

PMID- 11297518
TI  - Breast cancer. Cyr61 is overexpressed, estrogen-inducible, and associated with
      more advanced disease.
AB  - To identify genes involved in breast cancer, polymerase chain reaction-selected
      cDNA subtraction was utilized to construct a breast cancer-subtracted library.
      Differential screening of the library isolated the growth factor-inducible
      immediate-early gene Cyr61, a secreted, cysteine-rich, heparin binding protein
      that promotes endothelial cell adhesion, migration, and neovascularization.
      Northern analysis revealed that Cyr61 was expressed highly in the invasive breast
      cancer cell lines MDA-MB-231, T47D, and MDA-MB-157; very low levels were found in
      the less tumorigenic MCF-7 and BT-20 breast cancer cells and barely detectable
      amounts were expressed in the normal breast cells, MCF-12A. Univariate analysis
      showed a significant or borderline significant association between Cyr61
      expression and stage, tumor size, lymph node positivity, age, and estrogen
      receptor levels. Interestingly, expression of Cyr61 mRNA increased 8- to 12-fold
      in MCF-12A and 3- to 5-fold in MCF-7 cells after 24- and 48-h exposure to
      estrogen, respectively. Induction of Cyr61 mRNA was blocked by tamoxifen and
      ICI182,780, inhibitors of the estrogen receptor. Stable expression of Cyr61 cDNA
      under the regulation of a constitutive promoter in MCF-7 cells enhanced anchorage
      independent cell growth in soft agar and significantly increased tumorigenicity
      and vascularization of these tumors in nude mice. Moreover, overexpression of
      Cyr61 in MCF-12A normal breast cells induced their tumor formation and
      vascularization in nude mice. In summary, these results suggest that Cyr61 may
      play a role in the progression of breast cancer and may be involved in estrogen
      mediated tumor development.

PMID- 11297519
TI  - Mutagenic and nonmutagenic bypass of DNA lesions by Drosophila DNA polymerases
      dpoleta and dpoliota.
AB  - cDNA sequences were identified and isolated that encode Drosophila homologues of
      human Rad30A and Rad30B called drad30A and drad30B. Here we show that the C
      terminal-truncated forms of the drad30A and drad30B gene products, designated
      dpoletaDeltaC and dpoliotaDeltaC, respectively, exhibit DNA polymerase activity.
      dpoletaDeltaC and dpoliotaDeltaC efficiently bypass a cis-syn-cyclobutane thymine
      thymine (TT) dimer in a mostly error-free manner. dpoletaDeltaC shows limited
      ability to bypass a 6-4-photoproduct ((6-4)PP) at thymine-thymine (TT-(6-4)PP) or
      at thymine-cytosine (TC-(6-4)PP) in an error-prone manner. dpoliotaDeltaC
      scarcely bypasses these lesions. Thus, the fidelity of translesion synthesis
      depends on the identity of the lesion and on the polymerase. The human XPV gene
      product, hpoleta, bypasses cis-syn-cyclobutane thymine-thymine dimer efficiently
      in a mostly error-free manner but does not bypass TT-(6-4)PP, whereas Escherichia
      coli DNA polymerase V (UmuD'(2)C complex) bypasses both lesions, especially TT-(6
      4)PP, in an error-prone manner (Tang, M., Pham, P., Shen, X., Taylor, J. S.,
      O'Donnell, M., Woodgate, R., and Goodman, M. F. (2000) Nature 404, 1014-1018).
      Both dpoletaDeltaC and DNA polymerase V preferentially incorporate GA opposite TT
      (6-4)PP. The chemical structure of the lesions and the similarity in the
      nucleotides incorporated suggest that structural information in the altered bases
      contribute to nucleotide selection during incorporation opposite these lesions by
      these polymerases.

PMID- 11297520
TI  - Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome,
      LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its
      farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth.
AB  - Peutz-Jeghers syndrome is an inherited cancer syndrome that results in a greatly
      increased risk of developing tumors in those affected. The causative gene is a
      protein kinase termed LKB1, predicted to function as a tumor suppressor. The
      mechanism by which LKB1 is regulated in cells is not known. Here, we demonstrate
      that stimulation of Rat-2 or embryonic stem cells with activators of ERK1/2 or of
      cAMP-dependent protein kinase induced phosphorylation of endogenously expressed
      LKB1 at Ser(431). We present pharmacological and genetic evidence that p90(RSK)
      mediated this phosphorylation in response to agonists that activate ERK1/2 and
      that cAMP-dependent protein kinase mediated this phosphorylation in response to
      agonists that activate adenylate cyclase. Ser(431) of LKB1 lies adjacent to a
      putative prenylation motif, and we demonstrate that full-length LKB1 expressed in
      293 cells was prenylated by addition of a farnesyl group to Cys(433). Our data
      suggest that phosphorylation of LKB1 at Ser(431) does not affect farnesylation
      and that farnesylation does not affect phosphorylation at Ser(431).
      Phosphorylation of LKB1 at Ser(431) did not alter the activity of LKB1 to
      phosphorylate itself or the tumor suppressor protein p53 or alter the amount of
      LKB1 associated with cell membranes. The reintroduction of wild-type LKB1 into a
      cancer cell line that lacks LKB1 suppressed growth, but mutants of LKB1 in which
      Ser(431) was mutated to Ala to prevent phosphorylation of LKB1 were ineffective
      in inhibiting growth. In contrast, a mutant of LKB1 that cannot be prenylated was
      still able to suppress the growth of cells.

PMID- 11297521
TI  - Solution 1H NMR of the active site of substrate-bound, cyanide-inhibited human
      heme oxygenase. comparison to the crystal structure of the water-ligated form.
AB  - The majority of the active site residues of cyanide-inhibited, substrate-bound
      human heme oxygenase have been assigned on the basis of two-dimensional NMR using
      the crystal structure of the water-ligated substrate complex as a guide
      (Schuller, D. J., Wilks, A., Ortiz de Montellano, P. R., and Poulos, T. L. (1999)
      Nat. Struct. Biol. 6, 860-867). The proximal helix and the N-terminal portion of
      the distal helix are found to be identical to those in the crystal except that
      the heme for the major isomer ( approximately 75-80%) in solution is rotated 180
      degrees about the alpha-gamma-meso axis relative to the unique orientation in the
      crystal. The central portion of the distal helix in solution is translated
      slightly over the heme toward the distal ligand, and a distal four-ring aromatic
      cluster has moved 1-2 A closer to the heme, which allows for strong hydrogen
      bonds between the hydroxyls of Tyr-58 and Tyr-137. These latter interactions are
      proposed to stabilize the closed pocket conducive to the high stereospecificity
      of the alpha-meso ring opening. The determination of the magnetic axes, for which
      the major axis is controlled by the Fe-CN orientation, reveals a approximately 20
      degrees tilt of the distal ligand from the heme normal in the direction of the
      alpha-meso bridge, demonstrating that the close placement of the distal helix
      over the heme exerts control of stereospecificity by both blocking access to the
      beta, gamma, and delta-meso positions and tilting the axial ligand, a proposed
      peroxide, toward the alpha-meso position.

PMID- 11297522
TI  - Nuclear receptor response elements mediate induction of intestinal MDR1 by
      rifampin.
AB  - Intestinal P-glycoprotein, which is encoded by the MDR1 gene, plays an important
      role in the absorption and presystemic elimination of many xenobiotics. Hence, an
      understanding of the factors regulating its expression and function is of
      substantial interest. In addition to genetic factors, exposure to drugs such as
      rifampin can profoundly affect its expression. So far, the mechanisms by which
      rifampin induces MDR1 expression are poorly understood. Recent studies
      demonstrate that the nuclear receptor PXR (pregnane X receptor) is involved in
      xenobiotic induction of CYP3A4. Because CYP3A4 and MDR1 are often co-induced, we
      investigated whether a similar mechanism is also involved in MDR1 induction. The
      human colon carcinoma cell line LS174T was used as an intestinal model to study
      induction because in these cells the endogenous MDR1 gene is highly inducible by
      rifampin. The 5'-upstream region of human MDR1 was examined for the presence of
      potential PXR response elements. Several binding sites were identified that form
      a complex regulatory cluster at about -8 kilobase pairs. Only one DR4 motif
      within this cluster is necessary for induction by rifampin. We conclude that
      induction of MDR1 is mediated by a DR4 motif in the upstream enhancer at about -8
      kilobase pairs, to which PXR binds.

PMID- 11297523
TI  - A macrophage protein, Ym1, transiently expressed during inflammation is a novel
      mammalian lectin.
AB  - Oral infections of mice with Trichinella spiralis induce activation of peritoneal
      exudate cells to transiently express and secrete a crystallizable protein Ym1.
      Purification of Ym1 to homogeneity was achieved. It is a single chain polypeptide
      (45 kDa) with a strong tendency to crystallize at its isoelectric point (pI 5.7).
      Co-expression of Ym1 with Mac-1 and scavenger receptor pinpoints macrophages as
      its main producer. Protein microsequencing data provide information required for
      full-length cDNA cloning from libraries constructed from activated peritoneal
      exudate cells. A single open reading frame of 398 amino acids with a leader
      peptide (21 residues) typical of secretory protein was deduced and later
      deposited in GenBank (accession number M94584) in 1992. By means of surface
      plasmon resonance analyses, Ym1 has been shown to exhibit binding specificity to
      saccharides with a free amine group, such as GlcN, GalN, or GlcN polymers, but it
      failed to bind to other saccharides. The interaction is pH-dependent but Ca2+ and
      Mg2+ ion-independent. The binding avidity of Ym1 to GlcN oligosaccharides was
      enhanced by more than 1000-fold due to the clustering effect. Specific binding of
      Ym1 to heparin suggests that heparin/heparan sulfate may be its physiological
      ligand in vivo during inflammation and/or tissue remodeling. Although it shares
      approximately 30% homology with microbial chitinases, no chitinase activity was
      found associated with Ym1. Genomic Southern blot analyses suggest that Ym1 may
      represent a member of a novel lectin gene family.

PMID- 11297524
TI  - Differential expression of Vibrio vulnificus elastase gene in a growth phase
      dependent manner by two different types of promoters.
AB  - Elastase activity of Vibrio vulnificus was highly dependent on growth phase,
      reached a maximum during the stationary phase, and was regulated at the level of
      transcription. The stationary phase production of elastase in crp or rpoS
      mutants, which were constructed by allelic exchanges, decreased about 3- and 10
      fold, respectively. However, the promoter activity of vvpE encoding elastase was
      unaffected by those mutations in the log phase when analyzed using a vvpE-lux
      fusion. A primer extension analysis revealed that the transcription of vvpE
      begins at two different sites, consisting of putative promoter L (PL) and
      promoter S (PS). The PL activity was constitutive through the log and stationary
      phases, lower than the PS activity, and unaffected by the crp or rpoS mutations.
      The transcription of PS, induced only in the stationary phase, was dependent on
      RpoS. The mutation in crp reduced the activity of PS; however, the additional
      inactivation of crp did not influence the PS activity in the rpoS mutant,
      indicating that CRP exerted its effects through PS requiring RpoS. These results
      demonstrate that vvpE expression is differentially directed by PL and PS
      depending on the growth phase and elevated by RpoS and CRP in the stationary
      phase.

PMID- 11297525
TI  - Constitutive ERK1/2 activation in esophagogastric rib bone marrow micrometastatic
      cells is MEK-independent.
AB  - In this study, we examined the mitogen-activated protein kinase (MAPK) cascade in
      micrometastatic cell lines generated from rib bone marrow (RBM) of patients
      undergoing resection of esophagogastric malignancies. The molecular mechanism(s)
      involved in esophagogastric MAPK activation have not previously been
      investigated. Constitutive activation of both ERK1 and -2 isoforms was evident in
      each of the five RBM cell lines. Elk-1, a transcription factor activated by the
      ERK1/2 pathway was also found to be constitutively activated. Cell lines
      generated from metastases of involved lymph nodes (OC2) and ascites (OC1) of
      patients with esophageal cancer do not display, however, hyperphosphorylation of
      ERK1/2. Constitutive RBM ERK1/2 activation is protein kinase C and
      phosphatidylinositol 3-kinase dependent. Surprisingly, constitutive ERK1/2
      activation is MEK-independent. Pharmacological inhibition of MEK with two
      specific inhibitors, PD 98059 and U0126, were both ineffective in blocking ERK
      activation. Similarly, the use of a dominant negative MEK mutant was without
      effect. Interestingly, experiments overexpressing two different dominant negative
      Pak1 mutants significantly reduced RBM ERK1/2 activation, albeit not to the same
      extent for all cell lines. We also examined the role of three different
      phosphatases, PAC1, MKP-1, and -2. While RBM ERK1/2 activation was found to be
      PAC1- and MKP-2-independent, surprisingly, MKP-1 was down-regulated in all five
      RBM cell lines. In conclusion, we provide evidence for the first time for a MEK
      independent constitutive ERK1/2 activation pathway in esophagogastric RBM cell
      lines. These findings have important implications for drug treatment strategies
      which currently target MEK in other forms of cancer.

PMID- 11297526
TI  - Identification of receptor binding and activation determinants in the N-terminal
      and N-loop regions of the CC chemokine eotaxin.
AB  - Eotaxin is a CC chemokine that specifically activates the receptor CCR3 causing
      accumulation of eosinophils in allergic diseases and parasitic infections. Twelve
      amino acid residues in the N-terminal (residues 1-8) and N-loop (residues 11-20)
      regions of eotaxin have been individually mutated to alanine, and the ability of
      the mutants to bind and activate CCR3 has been determined in cell-based assays.
      The alanine mutants at positions Thr(7), Asn(12), Leu(13), and Leu(20) show near
      wild type binding affinity and activity. The mutants T8A, N15A, and K17A have
      near wild type binding affinity for CCR3 but reduced receptor activation. A third
      class of mutants, S4A, V5A, R16A, and I18A, display significantly perturbed
      binding affinity for CCR3 while retaining the ability to activate or partially
      activate the receptor. Finally, the mutant Phe(11) has little detectable activity
      and 20-fold reduced binding affinity relative to wild type eotaxin, the most
      dramatic effect observed in both assays but less dramatic than the effect of
      mutating the corresponding residue in some other chemokines. Taken together, the
      results indicate that residues contributing to receptor binding affinity and
      those required for triggering receptor activation are distributed throughout the
      N-terminal and N-loop regions. This conclusion is in contrast to the separation
      of binding and activation functions between N-loop and N-terminal regions,
      respectively, that has been observed previously for some other chemokines.

PMID- 11297527
TI  - 5-Lipoxygenase interacts with coactosin-like protein.
AB  - We have recently identified coactosin-like protein (CLP) in a yeast two-hybrid
      screen using 5-lipoxygenase (5LO) as a bait. In this report, we demonstrate a
      direct interaction between 5LO and CLP. 5LO associated with CLP, which was
      expressed as a glutathione S-transferase fusion protein, in a dose-dependent
      manner. Coimmunoprecipitation experiments using epitope-tagged 5LO and CLP
      proteins transiently expressed in human embryonic kidney 293 cells revealed the
      presence of CLP in 5LO immunoprecipitates. In reciprocal experiments, 5LO was
      detected in CLP immunoprecipitates. Non-denaturing polyacrylamide gel
      electrophoresis and cross-linking experiments showed that 5LO binds CLP in a 1:1
      molar stoichiometry in a Ca(2+)-independent manner. Site-directed mutagenesis
      suggested an important role for lysine 131 of CLP in mediating 5LO binding. In
      view of the ability of CLP to bind 5LO and filamentous actin (F-actin), we
      determined whether CLP could physically link 5LO to actin filaments. However, no
      F-actin-CLP.5LO ternary complex was observed. In contrast, 5LO appeared to
      compete with F-actin for the binding of CLP. Moreover, 5LO was found to interfere
      with actin polymerization. Our results indicate that the 5LO-CLP and CLP-F-actin
      interactions are mutually exclusive and suggest a modulatory role for 5LO in
      actin dynamics.

PMID- 11297528
TI  - Evidence for a conserved role for CRKII and Rac in engulfment of apoptotic cells.
AB  - Apoptosis or programmed cell death occurs in multicellular organisms throughout
      life. The removal of apoptotic cells by phagocytes prevents secondary necrosis
      and inflammation and also plays a key role in tissue remodeling and regulating
      immune responses. The molecular mechanisms that regulate the engulfment of
      apoptotic cells are just beginning to be elucidated. Recent genetic studies in
      the nematode Caenorhabditis elegans have implicated at least six genes in the
      removal of apoptotic cell corpses. The gene products of ced-2, ced-5, and ced-10
      are thought to be part of a pathway that regulates the reorganization of the
      cytoskeleton during engulfment. The adapter proteins CrkII and Dock180 and the
      small GTPase Rac represent the mammalian orthologues of the ced-2, ced-5 and ced
      10 gene products, respectively. It is not known whether CrkII, Dock180, or Rac
      proteins have any role during engulfment in mammalian cells. Here we show, using
      stable cell lines and transient transfections, that overexpression of wild-type
      CrkII or an activated form of Rac1 enhances engulfment. Mutants of CrkII failed
      to mediate this increased engulfment. The higher CrkII-mediated uptake was
      inhibited by coexpression of a dominant negative form of Rac1 but not by a
      dominant a negative Rho protein; this suggested that Rac functions downstream of
      CrkII in this process, which is consistent with genetic studies in the worm that
      place ced-10 (rac) downstream of ced-2 (crk) in cell corpse removal. Taken
      together, these data suggest that CED-2/CrkII and CED-10/Rac are part of an
      evolutionarily conserved pathway in engulfment of apoptotic cells.

PMID- 11297529
TI  - N-methyl-D-aspartate receptors regulate a group of transiently expressed genes in
      the developing brain.
AB  - Mammalian brain development requires the transmission of electrical signals
      between neurons via the N-methyl-d-aspartate (NMDA) class of glutamate receptors.
      However, little is known about how NMDA receptors carry out this role. Here we
      report the first genes shown to be regulated by physiological levels of NMDA
      receptor function in developing neurons in vivo: NMDA receptor-regulated gene 1
      (NARG1), NARG2, and NARG3. These genes share several striking regulatory
      features. All three are expressed at high levels in the neonatal brain in regions
      of neuronal proliferation and migration, are dramatically down-regulated during
      early postnatal development, and are down-regulated by NMDA receptor function.
      NARG2 and NARG3 appear to be novel, while NARG1 is the mammalian homologue of a
      yeast N-terminal acetyltransferase that regulates entry into the G(o) phase of
      the cell cycle. The results suggest that highly specific NMDA receptor-dependent
      regulation of gene expression plays an important role in the transition from
      proliferation of neuronal precursors to differentiation of neurons.

PMID- 11297530
TI  - Manganese superoxide dismutase signals matrix metalloproteinase expression via
      H2O2-dependent ERK1/2 activation.
AB  - Manganese-superoxide dismutase (Sod2) removes mitochondrially derived superoxide
      (O(2)) at near-diffusion limiting rates and is the only antioxidant enzyme whose
      expression is regulated by numerous stimuli. Here it is shown that Sod2 also
      serves as a source of the intracellular signaling molecule H(2)O(2). Sod2
      dependent increases in the steady-state levels of H(2)O(2) led to ERK1/2
      activation and subsequent downstream transcriptional increases in matrix
      metalloproteinase-1 (MMP-1) expression, which were reversed by expression of the
      H(2)O(2)-detoxifying enzyme, catalase. In addition, a single nucleotide
      polymorphism has recently been identified (1G/2G) at base pair--1607 that creates
      an Ets site adjacent to an AP-1 site at base pair --1602 and has been shown to
      dramatically enhance transcription of the MMP-1 promoter. Luciferase promoter
      constructs containing either the 1G or 2G variation were 25- or 1000-fold more
      active when transiently transfected into Sod2-overexpressing cell lines,
      respectively. The levels of MMP-2, -3, and -7 were also increased in the Sod2
      overexpressing cell lines, suggesting that Sod2 may function as a "global" redox
      regulator of MMP expression. In addition, Sod2(-/+) mouse embryonic fibroblasts
      failed to respond to the cytokine-mediated induction of the murine functional
      analog of MMP-1, MMP-13. This study provides evidence that the modulation of Sod2
      activity by a wide array of pathogenic and inflammatory stimuli may be utilized
      by the cell as a primary signaling mechanism leading to matrix metalloproteinase
      expression.

PMID- 11297531
TI  - A role for Hsc70 in regulating nucleocytoplasmic transport of a temperature
      sensitive p53 (p53Val-135).
AB  - Mouse temperature-sensitive p53(Val-135) accumulates in the nucleus and acts as a
      "wild-type" at 32 degrees C while it is sequestered in the cytoplasm at 37
      degrees C. The cytoplasmic p53(Val-135) relocalized into the nucleus upon
      inhibition of the nuclear export at 37 degrees C, whereas a mutation in a major
      bipartite nuclear localization signal (NLS) caused constitutive cytoplasmic
      localization, indicating that it shuttled between the cytoplasm and the nucleus
      by its own nuclear export signal and NLS rather than tethered to cytoplasmic
      structures. Although the full-length p53(Val-135) did not bind the import
      receptor at 37 degrees C, a C-terminally truncated p53(Val-135) lacking residues
      326-390 did bind it. Molecular chaperones such as Hsc70 were associated with
      p53(Val-135) at 37 degrees C but not at 32 degrees C. When the nuclear export was
      blocked by leptomycin B, only a fraction lacking Hsc70 was specifically
      accumulated in the nucleus. Immunodepletion of Hsc70 from the reticulocyte lysate
      caused p53(Val-135) to bind the import receptor. This binding was blocked by
      supplying the cell extract containing Hsc70 but not by the addition of
      recombinant Hsc70 alone. We suggest that the association with the Hsc70
      containing complex prevents the NLS from the access of the import receptor
      through the C-terminal region of p53(Val-135) at 37 degrees C, whereas its
      dissociation at 32 degrees C allows rapid nuclear import.

PMID- 11297532
TI  - The structure of a human type III Fcgamma receptor in complex with Fc.
AB  - Fcgamma receptors mediate antibody-dependent inflammatory responses and
      cytotoxicity as well as certain autoimmune dysfunctions. Here we report the
      crystal structure of a human Fc receptor (FcgammaRIIIB) in complex with an Fc
      fragment of human IgG1 determined from orthorhombic and hexagonal crystal forms
      at 3.0- and 3.5-A resolution, respectively. The refined structures from the two
      crystal forms are nearly identical with no significant discrepancies between the
      coordinates. Regions of the C-terminal domain of FcgammaRIII, including the BC,
      C'E, FG loops, and the C' beta-strand, bind asymmetrically to the lower hinge
      region, residues Leu(234)-Pro(238), of both Fc chains creating a 1:1 receptor
      ligand stoichiometry. Minor conformational changes are observed in both the
      receptor and Fc upon complex formation. Hydrophobic residues, hydrogen bonds, and
      salt bridges are distributed throughout the receptor.Fc interface. Sequence
      comparisons of the receptor-ligand interface residues suggest a conserved binding
      mode common to all members of immunoglobulin-like Fc receptors. Structural
      comparison between FcgammaRIII.Fc and FcepsilonRI.Fc complexes highlights the
      differences in ligand recognition between the high and low affinity receptors.
      Although not in direct contact with the receptor, the carbohydrate attached to
      the conserved glycosylation residue Asn(297) on Fc may stabilize the conformation
      of the receptor-binding epitope on Fc. An antibody-FcgammaRIII model suggests two
      possible ligand-induced receptor aggregations.

PMID- 11297533
TI  - Recognition of IgG by Fcgamma receptor. The role of Fc glycosylation and the
      binding of peptide inhibitors.
AB  - Recently determined crystal structures of the complex between immunoglobulin
      constant regions (Fc) and their Fc-respective receptors (FcR) have revealed the
      detailed molecular interactions of this receptor-ligand pair. Of particular
      interest is the contribution of a glycosylation at Asn(297) of the C(H)2 domain
      of IgG to receptor recognition. The carbohydrate moieties are found outside the
      receptor.Fc interface in all receptor.Fc complex structures. To understand the
      role of glycosylation in FcR recognition, the receptor affinities of a
      deglycosylated IgG1 and its Fc fragment were determined by solution binding
      studies using surface plasmon resonance. The removal of carbohydrates resulted in
      a non-detectable receptor binding to the Fc alone and a 15- to 20-fold reduction
      of the receptor binding to IgG1, suggesting that the carbohydrates are important
      in the function of the FcgammaRIII. Structurally, the carbohydrates attached to
      Asn(297) fill the cavity between the C(H)2 domains of Fc functioning equivalently
      as a hydrophobic core. This may stabilize a favorable lower hinge conformation
      for the receptor binding. The structure of the complex also revealed the
      dominance of the lower hinge region in receptor.Fc recognition. To evaluate the
      potential of designing small molecular ligands to inhibit the receptor function,
      four lower hinge peptides were investigated for their ability to bind to the
      receptor FcgammaRIII. These peptides bind specifically to FcgammaRIII with
      affinities 20- to 100-fold lower than IgG1 and are able to compete with Fc in
      receptor binding. The results of peptide binding illustrate new ways of designing
      therapeutic compounds to block Fc receptor activation.

PMID- 11297534
TI  - Identification of the motif in versican G3 domain that plays a dominant-negative
      effect on astrocytoma cell proliferation through inhibiting versican secretion
      and binding.
AB  - This study was designed to investigate the mechanisms by which mutant versican
      constructs play a dominant-negative effect on astrocytoma cell proliferation.
      Although a mini-versican or a versican G3 construct promoted growth of U87
      astrocytoma cells, a mini-versican lacking epidermal growth factor (EGF) motifs
      (versicanDeltaEGF) and a G3 mutant (G3DeltaEGF) exerted a dominant-negative
      effect on cell proliferation. G3DeltaEGF-transfected cells formed smaller
      colonies, arrested cell cycle at G(1) phase, inhibited expression of cell cycle
      proteins cdk4 and cyclin D1, and contained multiple nucleoli. In cell surface
      binding assays, G3 products expressed in COS-7 cells and bacteria bound to U87
      cell surface. G3DeltaEGF products exhibited decreased binding activity, but
      higher levels of G3DeltaEGF products were able to inhibit the binding of G3 to
      the cell surface. G3DeltaEGF expression inhibited secretion of endogenous
      versican in astrocytoma cells and also inhibited the secretion of mini-versican
      in COS-7 cells co-transfected with the mini-versican and G3DeltaEGF constructs.
      The effect seems to depend on the expression efficiency of G3DeltaEGF, and it
      occurred via the carbohydrate recognition domain.

PMID- 11297535
TI  - Characterization of the methylation-sensitive promoter of the imprinted ZAC gene
      supports its role in transient neonatal diabetes mellitus.
AB  - ZAC is a recently isolated zinc finger protein that induces apoptosis and cell
      cycle arrest. The corresponding gene is imprinted maternally through an unknown
      mechanism and maps to 6q24-q25, within the minimal interval harboring the gene
      responsible for transient neonatal diabetes mellitus (TNDM) and a tumor
      suppressor gene involved in breast cancer. Because of its functional properties,
      imprinting status, and expression pattern in mammary cell lines and tumors, ZAC
      is the best candidate so far for both disease conditions. In the present work, we
      delineated ZAC genomic organization and mapped its transcriptional start site. It
      is noteworthy that the ZAC promoter localized to the CpG island harboring the
      methylation imprint associated with TNDM and methylation of this promoter
      silenced its activity. These data indicate that the methylation mark may have a
      direct effect on the silencing of the ZAC imprinted allele. Our findings further
      strengthen the hypothesis that ZAC is the gene responsible for TNDM and suggest a
      novel mechanism for ZAC inactivation in breast tumors.

PMID- 11297536
TI  - Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine
      phosphatase 1b in vivo and enhances the early insulin action cascade.
AB  - The insulin signaling pathway is activated by tyrosine phosphorylation of the
      insulin receptor and key post-receptor substrate proteins and balanced by the
      action of specific protein-tyrosine phosphatases (PTPases). PTPase activity, in
      turn, is highly regulated in vivo by oxidation/reduction reactions involving the
      cysteine thiol moiety required for catalysis. Here we show that insulin
      stimulation generates a burst of intracellular H(2)O(2) in insulin-sensitive
      hepatoma and adipose cells that is associated with reversible oxidative
      inhibition of up to 62% of overall cellular PTPase activity, as measured by a
      novel method using strictly anaerobic conditions. The specific activity of
      immunoprecipitated PTP1B, a PTPase homolog implicated in the regulation of
      insulin signaling, was also strongly inhibited by up to 88% following insulin
      stimulation. Catalase pretreatment abolished the insulin-stimulated production of
      H(2)O(2) as well as the inhibition of cellular PTPases, including PTP1B, and was
      associated with reduced insulin-stimulated tyrosine phosphorylation of its
      receptor and high M(r) insulin receptor substrate (IRS) proteins. These data
      provide compelling new evidence for a redox signal that enhances the early
      insulin-stimulated cascade of tyrosine phosphorylation by oxidative inactivation
      of PTP1B and possibly other tyrosine phosphatases.

PMID- 11297537
TI  - p27Kip1 regulates T cell proliferation.
AB  - Our studies addressed the mechanism by which serum acts in conjunction with T
      cell receptor (TCR) agonists to promote the proliferation of primary splenic T
      cells. When added to resting splenocytes, TCR agonists initiated G(0)/G(1)
      traverse and activated cyclin D3-cdk6 complexes in a serum-independent manner. On
      the other hand, both TCR agonists and 10% serum were required for the activation
      of cyclin E-cdk2 and cyclin A-cdk2 complexes and the entry of cells into S phase.
      Serum facilitated cdk2 activation by maximizing the extent and extending the
      duration of the TCR-initiated down-regulation of the cdk2 inhibitor, p27(Kip1).
      Although p27(Kip1) levels were reduced (albeit submaximally) in cells stimulated
      in serum-deficient medium, nearly all of the cdk2 complexes in these cells
      contained p27(Kip1). In contrast, in cells receiving TCR agonist and 10% serum,
      little if any p27(Kip1) was present in cyclin-cdk2 complexes. Unlike wild-type
      splenocytes, p27(Kip1)-null splenocytes did not require serum for cdk2 activation
      or S phase entry whereas loss of the related cdk2 inhibitor, p21(Cip1), did not
      override the serum dependence of these responses. We also found that cdk2
      activation was both necessary and sufficient for maximal expression of cdk2
      protein. These studies provide a mechanistic basis for the serum dependence of T
      cell mitogenesis.

PMID- 11297538
TI  - Hyperosmolarity reduces GLUT4 endocytosis and increases its exocytosis from a
      VAMP2-independent pool in l6 muscle cells.
AB  - The intracellular traffic of the glucose transporter 4 (GLUT4) in muscle cells
      remains largely unexplored. Here we make use of L6 myoblasts stably expressing
      GLUT4 with an exofacially directed Myc-tag (GLUT4myc) to determine the exocytic
      and endocytic rates of the transporter. Insulin caused a rapid (t(12) = 4 min)
      gain, whereas hyperosmolarity (0.45 m sucrose) caused a slow (t(12) = 20 min)
      gain in surface GLUT4myc molecules. With prior insulin stimulation followed by
      addition of hypertonic sucrose, the increase in surface GLUT4myc was partly
      additive. Unlike the effect of insulin, the GLUT4myc gain caused by
      hyperosmolarity was insensitive to wortmannin or to tetanus toxin cleavage of
      VAMP2 and VAMP3. Disappearance of GLUT4myc from the cell surface was rapid (t(12)
      = 1.5 min). Insulin had no effect on the initial rate of GLUT4myc
      internalization. In contrast, hyperosmolarity almost completely abolished
      GLUT4myc internalization. Surface GLUT4myc accumulation in response to
      hyperosmolarity was only partially blocked by inhibition of tyrosine kinases with
      erbstatin analog (erbstatin A) and genistein. However, neither inhibitor
      interfered with the ability of hyperosmolarity to block GLUT4myc internalization.
      We propose that hyperosmolarity increases surface GLUT4myc by preventing GLUT4
      endocytosis and stimulating its exocytosis via a pathway independent of
      phosphatidylinositol 3-kinase activity and of VAMP2 or VAMP3. A tetanus toxin
      insensitive v-SNARE such as TI-VAMP detected in these cells, might mediate
      membrane fusion of the hyperosmolarity-sensitive pool.

PMID- 11297539
TI  - Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by
      disrupting Sp1 transcription factor interactions with a composite element in the
      CDK6 gene promoter.
AB  - Indole-3-carbinol (I3C), a compound naturally occurring in Brassica vegetables,
      can induce a G(1) cell cycle arrest of human MCF-7 breast cancer cells that is
      accompanied by the selective inhibition of cyclin-dependent kinase 6 (CDK6)
      expression. Reverse transcriptase-polymerase chain reaction analysis of CDK6 mRNA
      decay rates revealed that I3C had no effect on CDK6 transcript stability. We
      report the first identification and functional characterization of the CDK6
      promoter in order to determine whether I3C inhibits CDK6 transcription. In MCF-7
      cells stably transfected with CDK6 promoter-linked luciferase reporter plasmids,
      I3C inhibited CDK6 promoter activity in an I3C-specific response that was not a
      consequence of the growth-arrested state of the cells. Deletion analysis revealed
      a 167-base pair I3C-responsive region of the CDK6 promoter between -805 and -638.
      Site-specific mutations within this region revealed that both Sp1 and Ets-like
      sites, which are spaced 5 base pairs apart, were necessary for I3C responsiveness
      in the context of the CDK6 promoter. Electrophoretic mobility shift analysis of
      protein-DNA complexes formed with nuclear proteins isolated from I3C-treated and 
      untreated cells, in combination with supershift assays using Sp1 antibodies,
      demonstrated that the Sp1-binding site in the CDK6 promoter forms a specific I3C
      responsive DNA-protein complex that contains the Sp1 transcription factor. Taken
      together, our results suggest that I3C down-regulates CDK6 transcription by
      targeting Sp1 at a composite DNA site in the CDK6 promoter.

PMID- 11297540
TI  - MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation.
AB  - Regulation of p53 involves a complex network of protein interactions. The primary
      regulator of p53 protein stability is the Mdm2 protein. ARF and MdmX are two
      proteins that have recently been shown to inhibit Mdm2-mediated degradation of
      p53 via distinct associations with Mdm2. We demonstrate here that ARF is capable
      of interacting with MdmX and in a manner similar to its association with Mdm2,
      sequestering MdmX within the nucleolus. The sequestration of MdmX by ARF results
      in an increase in p53 transactivation. In addition, the redistribution of MdmX by
      ARF requires that a nucleolar localization signal be present on MdmX. Although
      expression of either MdmX or ARF leads to Mdm2 stabilization, coexpression of
      both MdmX and ARF results in a decrease in Mdm2 protein levels. Similarly,
      increasing ARF protein levels in the presence of constant MdmX and Mdm2 leads to
      a dose-dependent decrease in Mdm2 levels. Under these conditions, ARF can
      synergistically reverse the ability of Mdm2 and MdmX to inhibit p53-dependent
      transactivation. Finally, the association and redistribution of MdmX by ARF has
      no effect on the protein stability of either ARF or MdmX. Taken together, these
      results demonstrate that the interaction between MdmX and ARF represents a novel
      pathway for regulating Mdm2 protein levels. Additionally, both MdmX and Mdm2,
      either individually or together, are capable of antagonizing the effects of the
      ARF tumor suppressor on p53 activity.

PMID- 11297542
TI  - Cooperativity between the preproinsulin mRNA untranslated regions is necessary
      for glucose-stimulated translation.
AB  - Glucose regulates proinsulin biosynthesis via stimulation of the translation of
      the preproinsulin mRNA in pancreatic beta-cells. However, the mechanism by which
      this occurs has remained unclear. Using recombinant adenoviruses that express the
      preproinsulin mRNA with defined alterations, the untranslated regions (UTRs) of
      the preproinsulin mRNA were examined for elements that specifically control
      translation of the mRNA in rat pancreatic islets. These studies revealed that the
      preproinsulin 5'-UTR was necessary for glucose stimulation of preproinsulin mRNA
      translation, whereas the 3'-UTR appeared to suppress translation. However,
      together the 5'- and 3'-UTRs acted cooperatively to markedly increase glucose
      induced proinsulin biosynthesis. In primary hepatocytes the presence of the
      preproinsulin 3'-UTR led to reduced mRNA levels compared with the presence of the
      SV40 3'-UTR, consistent with the presence of mRNA stability determinants in the
      3'-UTR that stabilize the preproinsulin mRNA in a pancreatic beta-cell-specific
      manner. Translation of these mRNAs in primary hepatocytes was not stimulated by
      glucose, indicating that regulated translation of the preproinsulin mRNA occurs
      in a pancreatic beta-cell-specific manner. Thus, the untranslated regions of the
      preproinsulin mRNA play crucial roles in regulating insulin production and
      therefore glucose homeostasis by regulating the translation and the stability of
      the preproinsulin mRNA.

PMID- 11297541
TI  - Transforming growth factor-beta - and tumor necrosis factor-alpha -mediated
      induction and proteolytic activation of MMP-9 in human skin.
AB  - Both cytokines and matrix metalloproteinases (MMPs) are active during physiologic
      and pathologic processes such as cancer metastasis and wound repair. We have
      systematically studied cytokine-mediated MMP regulation. Cytokine-mediated
      proteinase induction and activation were initially investigated in organ-cultured
      human skin followed by determination of underlying cellular and molecular
      mechanisms using isolated skin cells. In this report we demonstrate that tumor
      necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta)
      synergistically induce pro-MMP-9 in human skin as well as isolated dermal
      fibroblasts and epidermal keratinocytes. Furthermore, TNF-alpha promotes
      proteolytic activation of pro-MMP-9 by conversion of the 92-kDa pro-MMP-9 to the
      82-kDa active enzyme. This activation occurred only in skin organ culture and not
      by either isolated fibroblasts or keratinocyte, although the pro-MMP-9 activation
      could be measured in a cell-free system derived from TNF-alpha-activated skin.
      The cytokine-mediated induction of pro-MMP-9 in dermal fibroblasts was evident by
      increased mRNA. At the transcription level, we examined the cytokine-mediated
      transactivation of the 5'-region promoter of the human MMP-9 in dermal
      fibroblasts. The results demonstrated that TNF-alpha and TGF-beta could
      independently stimulate the 5'-flanking 670-base pair promoter. A TGF-beta
      response element (-474) and an NF-kappaB-binding site (-601) were identified to
      be the cis-elements for TGF-beta or TNF-alpha activation, respectively. Taken
      together, these findings suggest a specific mechanism whereby multiple cytokines
      can regulate MMP-9 expression/activation in the cells of human skin. These
      results imply roles for these cytokines in the regulation of MMP-9 in physiologic
      and pathologic tissue remodeling.

PMID- 11297543
TI  - Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial
      and nuclear isoforms.
AB  - Glutaredoxin (Grx) is a glutathione-dependent hydrogen donor for ribonucleotide
      reductase. Today glutaredoxins are known as a multifunctional family of GSH
      disulfide-oxidoreductases belonging to the thioredoxin fold superfamily. In
      contrast to Escherichia coli and yeast, a single human glutaredoxin is known. We
      have identified and cloned a novel 18-kDa human dithiol glutaredoxin, named
      glutaredoxin-2 (Grx2), which is 34% identical to the previously known cytosolic
      12-kDa human Grx1. The human Grx2 sequence contains three characteristic regions
      of the glutaredoxin family: the dithiol/disulfide active site, CSYC, the GSH
      binding site, and a hydrophobic surface area. The human Grx2 gene, located at
      chromosome 1q31.2--31.3, consisted of five exons that were transcribed to a 0.9
      kilobase human Grx2 mRNA ubiquitously expressed in several tissues. Two
      alternatively spliced Grx2 mRNA isoforms that differed in their 5' region were
      identified. These corresponded to alternative proteins with a common 125-residue
      C-terminal Grx domain but with different N-terminal extensions of 39 and 40
      residues, respectively. The 125-residue Grx domain and the two full-length
      variants were expressed in E. coli and exhibited GSH-dependent hydroxyethyl
      disulfide and dehydroascorbate reducing activities. Western blot analysis of
      subcellular fractions from Jurkat cells with a specific anti-Grx2 antibody showed
      that human Grx2 was predominantly located in the nucleus but also present in the
      mitochondria. We further showed that one of the mRNA isoforms corresponding to
      Grx2a encoded a functional N-terminal mitochondrial translocation signal.

PMID- 11297544
TI  - Molecular characterization of peripherin-2 and rom-1 mutants responsible for
      digenic retinitis pigmentosa.
AB  - Peripherin-2 and Rom-1 are homologous tetraspanning membrane proteins that
      assemble into noncovalent tetramers and higher order disulfide-linked oligomers
      implicated in photoreceptor disc morphogenesis. Individuals who coinherit a L185P
      peripherin-2 mutation and a null or G113E rom-1 mutation are afflicted with
      retinitis pigmentosa, whereas individuals who inherit only one defective gene are
      normal. We examined the expression, subunit assembly, and disulfide-mediated
      oligomerization of L185P and L185A peripherin-2 and L188P Rom-1 by velocity
      sedimentation, co-immunoprecipitation, and cross-linking. These mutants formed
      noncovalent dimers under disulfide-reducing conditions but failed to assemble
      into core tetramers. Under nonreducing conditions, L185P dimers formed disulfide
      linked tetramers but not higher order oligomers. L185P coassembled with wild-type
      peripherin-2 and Rom-1 to form tetramers and higher order disulfide-linked
      oligomers characteristic of the wild-type proteins. The G113E Rom-1 mutant
      expressed 20-fold lower than wild-type Rom-1, indicating that it behaves
      mechanistically as a null allele. We conclude that Leu(185) of peripherin-2
      (Leu(188) of Rom-1) is critical for tetramer but not dimer formation and that the
      core tetramer has 2-fold symmetry. Peripherin-2-containing tetramers are required
      for higher order disulfide-linked oligomer formation. The level of these
      oligomers is critical for stable photoreceptor disc formation and the digenic
      retinitis pigmentosa disease phenotype.

PMID- 11297545
TI  - Autocrine human growth hormone (hGH) regulation of human mammary carcinoma cell
      gene expression. Identification of CHOP as a mediator of hGH-stimulated human
      mammary carcinoma cell survival.
AB  - By use of cDNA array technology we have screened 588 genes to determine the
      effect of autocrine production of human growth hormone (hGH) on gene expression
      in human mammary carcinoma cells. We have used a previously described cellular
      model to study autocrine hGH function in which the hGH gene or a translation
      deficient hGH gene was stably transfected into MCF-7 cells. Fifty two of the
      screened genes were regulated, either positively () or negatively (), by
      autocrine production of hGH. We have now characterized the role of one of the up
      regulated genes, chop (gadd153), in the effect of autocrine production of hGH on
      mammary carcinoma cell number. The effect of autocrine production of hGH on the
      level of CHOP mRNA was exerted at the transcriptional level as autocrine hGH
      increased chloramphenicol acetyltransferase production from a reporter plasmid
      containing a 1-kilobase pair fragment of the chop promoter. The autocrine hGH
      stimulated increase in CHOP mRNA also resulted in an increase in CHOP protein. As
      a consequence, autocrine hGH stimulation of CHOP-mediated transcriptional
      activation was increased. Stable transfection of human CHOP cDNA into mammary
      carcinoma cells demonstrated that CHOP functioned not as a mediator of hGH
      stimulated mitogenesis but rather enhanced the protection from apoptosis afforded
      by hGH in a p38 MAPK-dependent manner. Thus transcriptional up-regulation of chop
      is one mechanism by which hGH regulates mammary carcinoma cell number.

PMID- 11297546
TI  - Inhibition of the Wnt signaling pathway by the PR61 subunit of protein
      phosphatase 2A.
AB  - Axin, a negative regulator of the Wnt signaling pathway, forms a complex with
      glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, adenomatous polyposis
      coli (APC) gene product, and Dvl, and it regulates GSK-3beta-dependent
      phosphorylation in the complex and the stability of beta-catenin. Using yeast two
      hybrid screening, we found that regulatory subunits of protein phosphatase 2A,
      PR61beta and -gamma, interact with Axin. PR61beta or -gamma formed a complex with
      Axin in intact cells, and their interaction was direct. The binding site of
      PR61beta on Axin was different from those of GSK-3beta, beta-catenin, APC, and
      Dvl. Although PR61beta did not affect the stability of beta-catenin, it inhibited
      Dvl- and beta-catenin-dependent T cell factor activation in mammalian cells.
      Moreover, it suppressed beta-catenin-induced axis formation and expression of
      siamois, a Wnt target gene, in Xenopus embryos, suggesting that PR61beta acts
      either at the level of beta-catenin or downstream of it. Taken together with the
      previous observations that PR61 interacts with APC and functions upstream of beta
      catenin, these results demonstrate that PR61 regulates the Wnt signaling pathway
      at various steps.

PMID- 11297547
TI  - Structural evidence for entropic contribution of salt bridge formation to a
      protein antigen-antibody interaction: the case of hen lysozyme-HyHEL-10 Fv
      complex.
AB  - A structural and thermodynamic study of the entropic contribution of salt bridge
      formation to the interaction between hen egg white lysozyme (HEL) and the
      variable domain fragment (Fv) of anti-HEL antibody, HyHEL-10, was carried out.
      Three Fv mutants (HD32A, HD96A, and HD32AD96A) were prepared, and the
      interactions between the mutant Fvs and HEL were investigated. Crystallography
      revealed that the overall structures of these mutant complexes were almost
      identical to that of wild-type Fv. Little structural changes were observed in the
      HD32AD96A mutant-HEL complex, and two water molecules were introduced into the
      mutation site, indicating that the two water molecules structurally compensated
      for the complete removal of the salt bridges. This result suggests that the
      entropic contribution of the salt bridge originates from dehydration. In the
      singly mutated complexes, one water molecule was also introduced into the mutated
      site, bridging the antigen-antibody interface. However, a local structural
      difference was observed in the HD32A Fv-HEL complex, and conformational changes
      occurred due to changes in the relative orientation of the heavy chain to the
      light chain upon complexation in HD96A Fv-HEL complexes. The reduced affinity of
      these single mutants for the antigen originates from the increase in entropy
      loss, indicating that these structural changes also introduced an increase in
      entropy loss. These results suggest that salt bridge formation makes an entropic
      contribution to the protein antigen-antibody interaction through reduction of
      entropy loss due to dehydration and structural changes.

PMID- 11297548
TI  - Growth factor-specific signaling pathway stimulation and gene expression mediated
      by ErbB receptors.
AB  - The mechanisms by which receptor tyrosine kinases (RTKs) utilize intracellular
      signaling pathways to direct gene expression and cellular response remain
      unclear. A current question is whether different RTKs within a single cell target
      similar or different sets of genes. In this study we have used the ErbB receptor
      network to explore the relationship between RTK activation and gene expression.
      We profiled growth factor-stimulated signaling pathway usage and broad gene
      expression patterns in two human mammary tumor cell lines expressing different
      complements of ErbB receptors. Although the growth factors epidermal growth
      factor (EGF) and neuregulin (NRG) 1 similarly stimulated Erk1/2 in MDA-MB-361
      cells, EGF acting through an EGF receptor/ErbB2 heterodimer preferentially
      stimulated protein kinase C, and NRG1beta acting through an ErbB2/ErbB3
      heterodimer preferentially stimulated Akt. The two growth factors regulated
      partially overlapping yet distinct sets of genes in these cells. In MDA-MB-453
      cells, NRG1beta acting through an ErbB2/ErbB3 heterodimer stimulated prolonged
      signaling of all pathways examined relative to NRG2beta acting through the same
      heterodimeric receptor species. Surprisingly, NRG1beta and NRG2beta also
      regulated partially overlapping but distinct sets of genes in these cells. These
      results demonstrate that the activation of different RTKs, or activation of the
      same RTKs with different ligands, can lead to distinct profiles of gene
      regulation within a single cell type. Our observations also suggest that the
      identity and kinetics of signaling pathway usage by RTKs may play a role in the
      selection of regulated genes.

PMID- 11297549
TI  - IRP1 activation by extracellular oxidative stress in the perfused rat liver.
AB  - The expression of several proteins with critical functions in iron metabolism is
      regulated post-transcriptionally by the binding of iron regulatory proteins, IRP1
      and IRP2, to mRNA iron responsive elements (IREs). In iron-deficient tissues and
      cultured cells, both IRP1 and IRP2 are activated for high affinity IRE binding.
      Previous work showed that IRP1 is also activated when cultured cells are exposed
      to H(2)O(2). The well established role of iron and H(2)O(2) in tissue injury
      (based on Fenton chemistry) suggests that this response may have important
      pathophysiological implications. This is particularly relevant in inflammation,
      where cytotoxic immune cells release large amounts of reactive oxygen species.
      Here, we describe a rat liver perfusion model to study IRP1 activation under
      H(2)O(2) generation conditions that mimic a physiological inflammatory response,
      using steady-state concentrations of H(2)O(2) produced by a glucose/ glucose
      oxidase/catalase system. We show first that stimulated neutrophils are able to
      increase serum levels of H(2)O(2) by a factor of 10, even in the presence of
      H(2)O(2)-degrading erythrocytes. We further show that perfusion of rat liver with
      glucose oxidase leads to a rapid activation of IRE binding activity in the intact
      organ. Mobility shift assays with liver extracts and IRP1 or IRP2-specific probes
      indicate that only IRP1 responds to H(2)O(2). Our study demonstrates a principal
      existence of iron regulation by oxidative stress at the intact organ level. It
      also provides a link between iron metabolism and the inflammatory response, as
      H(2)O(2) is a major product of the oxidative burst of neutrophils and
      macrophages.

PMID- 11297550
TI  - Real time kinetics of insulin-like growth factor II (IGF-II) interaction with the
      IGF-II/mannose 6-phosphate receptor: the effects of domain 13 and pH.
AB  - The interaction of soluble forms of the human cation-independent insulin-like
      growth factor-II/mannose 6-phosphate receptor (IGF-IIR) with IGFs and
      mannosylated ligands was analyzed in real time. IGF-IIR proteins containing
      domains 1-15, 10-13, 11-13, or 11-12 were combined with rat CD4 domains 3 and 4.
      Following transient expression in 293T cells, secreted protein was immobilized
      onto biosensor chips. beta-Glucuronidase and latent transforming growth factor
      beta1 bound only to domains 1-15. IGF-II bound to all constructs except a
      control, which contained a point mutation in domain 11. The affinity of domains 1
      15, 10-13, 11-13, and 11-12 to IGF-II were 14, 120, 100, and 450 nm,
      respectively. Our data suggest that domain 13 acts as an enhancer of IGF-II
      affinity by slowing the rate of dissociation, but additional enhancement by
      domains other than 10-13 also occurs. As the receptor functions to transport
      ligands from either the trans-Golgi network or extracellular space to the
      endosomes, the interaction of IGF-IIR extracellular domains with IGF-II was
      analyzed over a pH range of 5.0-7.4. The constructs behaved differently in
      response to pH and in recovery after low pH exposure, suggesting that pH
      stability of the extracellular domains depends on domains other than 10-13.

PMID- 11297551
TI  - Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB
      kinase activity.
AB  - The sedative and anti-nausea drug thalidomide, which causes birth defects in
      humans, has been shown to have both anti-inflammatory and anti-oncogenic
      properties. The anti-inflammatory effect of thalidomide is associated with
      suppression of cytokine expression and the anti-oncogenic effect with inhibition
      of angiogenesis. It is presently unclear whether the teratogenic properties of
      thalidomide are connected in any way to the beneficial, anti-disease
      characteristics of this drug. The transcription factor NF-kappaB has been shown
      to be a key regulator of inflammatory genes such as tumor necrosis factor-alpha
      and interleukin-8. Inhibition of NF-kappaB is associated with reduced
      inflammation in animal models, such as those for rheumatoid arthritis. We show
      here that thalidomide can block NF-kappaB activation through a mechanism that
      involves the inhibition of activity of the IkappaB kinase. Consistent with the
      observed inhibition of NF-kappaB, thalidomide blocked the cytokine-induced
      expression of NF-kappaB-regulated genes such as those encoding interleukin-8,
      TRAF1, and c-IAP2. These data indicate that the therapeutic potential for
      thalidomide may be based on its ability to block NF-kappaB activation through
      suppression of IkappaB kinase activity.

PMID- 11297553
TI  - Differential effect of two stathmin/Op18 phosphorylation mutants on Xenopus
      embryo development.
AB  - Stathmin/Op18 destabilizes microtubules in vitro and regulates microtubule
      polymerization in vivo. Both a microtubule catastrophe-promoting activity and a
      tubulin sequestering activity were demonstrated for stathmin in vitro, and both
      could contribute to microtubule depolymerization in vivo. Stathmin activity can
      be turned down by extensive phosphorylation on its four phosphorylatable serines,
      and down-regulation of stathmin activity by phosphorylation is necessary for
      cells to proceed through mitosis. We show here that microinjection of a
      nonphosphorylatable Ser to Ala (4A) quadruple mutant in Xenopus two-cell stage
      embryos results in cell cleavage arrest in the injected blastomeres and aborted
      development, whereas injection of a pseudo-phosphorylated Ser to Glu quadruple
      mutant (4E) does not prevent normal development. Addition of these mutants to
      mitotic cytostatic factor-arrested extracts in which spindle assembly was induced
      led to a dramatic reduction of spindle size with 4A stathmin, and to a moderate
      increase with 4E stathmin, but both localized to spindle poles. Interestingly,
      the microtubule assembly-dependent phosphorylation of endogenous stathmin was
      abolished in the presence of 4A stathmin, but not of 4E stathmin. Altogether,
      this shows that the phosphorylation-mediated regulation of stathmin activity
      during the cell cycle is essential for early Xenopus embryonic development.

PMID- 11297552
TI  - Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to
      PDGF alpha and beta receptor.
AB  - We have characterized platelet-derived growth factor (PDGF) C, a novel growth
      factor belonging to the PDGF family. PDGF-C is a multidomain protein with the N
      terminal region homologous to the extracellular CUB domain of neuropilin-1, and
      the C-terminal region consists of a growth factor domain (GFD) with homology to
      vascular endothelial growth factor (25%) and PDGF A-chain (23%). A serum
      sensitive cleavage site between the two domains allows release of the GFD from
      the CUB domain. Competition binding and immunoprecipitation studies on cells
      bearing both PDGF alpha and beta receptors reveal a high affinity binding of
      recombinant GFD (PDGF-CC) to PDGF receptor-alpha homodimers and PDGF receptor
      alpha/beta heterodimers. PDGF-CC exhibits greater mitogenic potency than PDGF-AA
      and comparable or greater mitogenic activity than PDGF-AB and PDGF-BB on several
      mesenchymal cell types. Analysis of PDGF-CC in vivo in a diabetic mouse model of
      delayed wound healing showed that PDGF-CC significantly enhanced repair of a full
      thickness skin excision. Together, these studies describe a third member of the
      PDGF family (PDGF-C) as a potent mitogen for cells of mesenchymal origin in in
      vitro and in vivo systems with a binding pattern similar to PDGF-AB.

PMID- 11297554
TI  - Identification of a ryanodine receptor in rat heart mitochondria.
AB  - Recent studies have shown that, in a wide variety of cells, mitochondria respond
      dynamically to physiological changes in cytosolic Ca(2+) concentrations
      ([Ca(2+)](c)). Mitochondrial Ca(2+) uptake occurs via a ruthenium red-sensitive
      calcium uniporter and a rapid mode of Ca(2+) uptake. Surprisingly, the molecular
      identity of these Ca(2+) transport proteins is still unknown. Using electron
      microscopy and Western blotting, we identified a ryanodine receptor in the inner
      mitochondrial membrane with a molecular mass of approximately 600 kDa in
      mitochondria isolated from the rat heart. [(3)H]Ryanodine binds to this
      mitochondrial ryanodine receptor with high affinity. This binding is modulated by
      Ca(2+) but not caffeine and is inhibited by Mg(2+) and ruthenium red in the assay
      medium. In the presence of ryanodine, Ca(2+) uptake into isolated heart
      mitochondria is suppressed. In addition, ryanodine inhibited mitochondrial
      swelling induced by Ca(2+) overload. This swelling effect was not observed when
      Ca(2+) was applied to the cytosolic fraction containing sarcoplasmic reticulum.
      These results are the first to identify a mitochondrial Ca(2+) transport protein
      that has characteristics similar to the ryanodine receptor. This mitochondrial
      ryanodine receptor is likely to play an essential role in the dynamic uptake of
      Ca(2+) into mitochondria during Ca(2+) oscillations.

PMID- 11297555
TI  - Cloning and characterization of the human and rat islet-specific glucose-6
      phosphatase catalytic subunit-related protein (IGRP) genes.
AB  - Islet-specific glucose-6-phosphatase (G6Pase) catalytic subunit-related protein
      (IGRP) is a homolog of the catalytic subunit of G6Pase, the enzyme that catalyzes
      the terminal step of the gluconeogenic pathway. Its catalytic activity, however,
      has not been defined. Since IGRP gene expression is restricted to islets, this
      suggests a possible role in the regulation of islet metabolism and, hence,
      insulin secretion induced by metabolites. We report here a comparative analysis
      of the human, mouse, and rat IGRP genes. These studies aimed to identify
      conserved sequences that may be critical for IGRP function and that specify its
      restricted tissue distribution. The single copy human IGRP gene has five exons of
      similar length and coding sequence to the mouse IGRP gene and is located on human
      chromosome 2q28-32 adjacent to the myosin heavy chain 1B gene. In contrast, the
      rat IGRP gene does not appear to encode a protein as a result of a series of
      deletions and insertions in the coding sequence. Moreover, rat IGRP mRNA, unlike
      mouse and human IGRP mRNA, is not expressed in islets or islet-derived cell
      lines, an observation that was traced by fusion gene analysis to a mutation of
      the TATA box motif in the mouse/human IGRP promoters to TGTA in the rat sequence.
      The results provide a framework for the further analysis of the molecular basis
      for the tissue-restricted expression of the IGRP gene and the identification of
      key amino acid sequences that determine its biological activity.

PMID- 11297556
TI  - Two functionally distinct steps mediate high affinity binding of U1A protein to
      U1 hairpin II RNA.
AB  - Binding of the U1A protein to its RNA target U1 hairpin II has been extensively
      studied as a model for a high affinity RNA/protein interaction. However, the
      mechanism and kinetics by which this complex is formed remain largely unknown.
      Here we use real-time biomolecular interaction analysis to dissect the roles
      various protein and RNA structural elements play in the formation of the U1A.U1
      hairpin II complex. We show that neutralization of positive charges on the
      protein or increasing the salt concentration slows the association rate,
      suggesting that electrostatic interactions play an important role in bringing RNA
      and protein together. In contrast, removal of hydrogen bonding or stacking
      interactions within the RNA/protein interface, or reducing the size of the RNA
      loop, dramatically destabilizes the complex, as seen by a strong increase in the
      dissociation rate. Our data support a binding mechanism consisting of a rapid
      initial association based on electrostatic interactions and a subsequent locking
      step based on close-range interactions that occur during the induced fit of RNA
      and protein. Remarkably, these two steps can be clearly distinguished using U1A
      mutants containing single amino acid substitutions. Our observations explain the
      extraordinary affinity of U1A for its target and may suggest a general mechanism
      for high affinity RNA/protein interactions.

PMID- 11297557
TI  - Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine
      927 is essential for signal-induced p105 proteolysis.
AB  - The p105 precursor protein of NF-kappaB1 acts as an NF-kappaB inhibitory protein,
      retaining associated Rel subunits in the cytoplasm of unstimulated cells. Tumor
      necrosis factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) stimulate
      p105 degradation, releasing associated Rel subunits to translocate into the
      nucleus. By using knockout embryonic fibroblasts, it was first established that
      the IkappaB kinase (IKK) complex is essential for these pro-inflammatory
      cytokines to trigger efficiently p105 degradation. The p105 PEST domain contains
      a motif (Asp-Ser(927)-Gly-Val-Glu-Thr), related to the IKK target sequence in
      IkappaBalpha, which is conserved between human, mouse, rat, and chicken p105.
      Analysis of a panel of human p105 mutants in which serine/threonine residues
      within and adjacent to this motif were individually changed to alanine
      established that only serine 927 is essential for p105 proteolysis triggered by
      IKK2 overexpression. This residue is also required for TNFalpha and IL-1alpha to
      stimulate p105 degradation. By using a specific anti-phosphopeptide antibody, it
      was confirmed that IKK2 overexpression induces serine 927 phosphorylation of co
      transfected p105 and that endogenous p105 is also rapidly phosphorylated on this
      residue after TNFalpha or IL-1alpha stimulation. In vitro kinase assays with
      purified proteins demonstrated that both IKK1 and IKK2 can directly phosphorylate
      p105 on serine 927. Together these experiments indicate that the IKK complex
      regulates the signal-induced proteolysis of NF-kappaB1 p105 by direct
      phosphorylation of serine 927 in its PEST domain.

PMID- 11297558
TI  - Molecular analysis of the epidermal growth factor-like short consensus repeat
      domain-mediated protein-protein interactions: dissection of the CD97-CD55
      complex.
AB  - Epidermal growth factor-like (EGF) and short consensus repeat (SCR) domains are
      commonly found in cell surface and soluble proteins that mediate specific protein
      protein recognition events. Unlike the immunoglobulin (Ig) superfamily, very
      little is known about the general properties of intermolecular interactions
      encoded by these common modules, and in particular, how specificity of binding is
      achieved. We have dissected the binding of CD97 (a member of the EGF-TM7 family)
      to the complement regulator CD55, two cell surface modular proteins that contain
      EGF and SCR domains, respectively. We demonstrate that the interaction is
      mediated solely by these domains and is characterized by a low affinity (86
      microm) and rapid off-rate (at least 0.6 s(-1)). The interaction is Ca(2+) 
      dependent but is unaffected by glycosylation of the EGF domains. Using
      biotinylated multimerized peptides in cell binding assays and surface plasmon
      resonance, we show that a CD97-related EGF-TM7 molecule (termed EMR2), differing
      by only three amino acids within the EGF domains, binds CD55 with a K(D) at least
      an order of magnitude weaker than that of CD97. These results suggest that low
      affinity cell-cell interactions may be a general feature of highly expressed cell
      surface proteins and that specificity of SCR-EGF binding can be finely tuned by a
      small number of amino acid changes on the EGF module surface.

PMID- 11297559
TI  - Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA
      damage- and cell cycle-regulated manner.
AB  - Fanconi anemia (FA) is a genetic disease characterized by congenital defects,
      bone marrow failure, and cancer susceptibility. Cells from patients with FA
      exhibit genomic instability and hypersensitivity to DNA cross linking agents such
      as mitomycin C. Despite the identification of seven complementation groups and
      the cloning of six genes, the function of the encoded gene products remains
      elusive. The FancA (Fanconi anemia complementation group A), FancC, and FancG
      proteins have been detected within a nuclear complex, but no change in level,
      binding, or localization has been reported as a result of drug treatment or cell
      cycle. We show that in immunofluorescence studies, FancA appears as a non
      nucleolar nuclear protein that is excluded from condensed, mitotic chromosomes.
      Biochemical fractionation reveals that the FA proteins are found in nuclear
      matrix and chromatin and that treatment with mitomycin C results in increase of
      the FA proteins in nuclear matrix and chromatin fractions. This induction occurs
      in wild-type cells and mutant FA-D (Fanconi complementation group D) cells but
      not in mutant FA-A cells. Immunoprecipitation of FancA protein in chromatin
      demonstrates the coprecipitation of FancA, FancC, and FancG, showing that the FA
      proteins move together as a complex. Also, fractionation of mitotic cells
      confirms the lack of FA proteins in chromatin or the nuclear matrix. Furthermore,
      phosphorylation of FancG was found to be temporally correlated with exit of the
      FA complex from chromosomes at mitosis. Taken together, these findings suggest a
      role for FA proteins in chromatin and nuclear matrix.

PMID- 11297560
TI  - Suppressor of cytokine signaling 1 interacts with the macrophage colony
      stimulating factor receptor and negatively regulates its proliferation signal.
AB  - Macrophage colony-stimulating factor receptor (M-CSF-R) is a tyrosine kinase that
      regulates proliferation, differentiation, and cell survival during monocytic
      lineage development. Upon activation, M-CSF-R dimerizes and autophosphorylates on
      specific tyrosines, creating binding sites for several cytoplasmic SH2-containing
      signaling molecules that relay and modulate the M-CSF signal. Here we show that M
      CSF-R interacts with suppressor of cytokine signaling 1 (Socs1), a negative
      regulator of various cytokine and growth factor signaling pathways. Using the
      yeast two-hybrid system, in vitro glutathione S-transferase-M-CSF-R pull-down,
      and in vivo coimmunoprecipitation experiments, we demonstrated a direct
      interaction between the SH2 domain of Socs1 and phosphorylated tyrosines 697 or
      721 of the M-CSF-R kinase insert region. Moreover, Socs1 is tyrosine
      phosphorylated in response to M-CSF. Ectopic expression of Socs1 in FDC-P1/MAC
      and EML hematopoietic cell lines decreased their growth rates in the presence of
      limiting concentrations of M-CSF. However, Socs1 expression did not totally
      suppress long term cell growth in the presence of saturating M-CSF
      concentrations, in contrast to other cytokines such as stem cell factor and
      interleukin 3. Taken together, these results suggest that Socs1 is an M-CSF-R
      binding partner involved in negative regulation of proliferation signaling and
      that it differentially affects cytokine receptor signals.

PMID- 11297561
TI  - Diffusion in the endoplasmic reticulum of an aquaporin-2 mutant causing human
      nephrogenic diabetes insipidus.
AB  - Mutations in the aquaporin-2 (AQP2) water channel cause the hereditary renal
      disease nephrogenic diabetes insipidus (NDI). The missense mutation AQP2-T126M
      causes human recessive NDI by retention at the endoplasmic reticulum (ER) of
      renal epithelial cells. To determine whether the ER retention of AQP2-T126M is
      due to relative immobilization in the ER, we measured by fluorescence recovery
      after photobleaching the intramembrane mobility of green fluorescent protein
      (GFP) chimeras containing human wild-type and mutant AQP2. In transfected LLC-PK1
      renal epithelial cells, GFP-labeled AQP2-T126M was localized to the ER, and wild
      type AQP2 to endosomes and the plasma membrane; both were localized to the ER
      after brefeldin A treatment. Photobleaching with image detection indicated that
      the GFP-AQP2 chimeras were freely mobile throughout the ER. Quantitative spot
      photobleaching revealed a diffusion-dependent irreversible process whose recovery
      depended on spot size and was abolished by paraformaldehyde fixation. In
      addition, a novel slow reversible fluorescence recovery (t(12) approximately 2 s)
      was characterized whose recovery was independent of spot size and not affected by
      fixation. AQP2 translational diffusion in the ER was not slowed by the T126M
      mutation; diffusion coefficients were (in cm(2)/s x 10(-)10) 2.6 +/- 0.5 (wild
      type) and 3.0 +/- 0.4 (T126M). Much faster diffusion was found for a lipid probe
      (diOC(4)(3), 2.7 x 10(-)8 cm(2)/s) in the ER membrane and for unconjugated GFP in
      the aqueous ER lumen (6 x 10(-)8 cm(2)/s). ER diffusion of GFP-T126M was not
      significantly affected by up-regulation of molecular chaperones, cAMP activation,
      or actin filament disruption. ATP depletion by 2-deoxyglucose and azide resulted
      in comparable slowing/immobilization of wild-type and T126M AQP2. These results
      indicate that the ER retention of AQP2-T126M does not result from restricted or
      slowed mobility and suggest that the majority of AQP2-T126M is not aggregated or
      bound to slowly moving membrane proteins.

PMID- 11297562
TI  - Passive entry of CO2 and its energy-dependent intracellular conversion to HCO3-
      in cyanobacteria are driven by a photosystem I-generated deltamuH+.
AB  - CO(2) entry into Synechococcus sp. PCC7942 cells was drastically inhibited by the
      water channel blocker p-chloromercuriphenylsulfonic acid suggesting that CO(2)
      uptake is, for the most part, passive via aquaporins with subsequent energy
      dependent conversion to HCO3(-). Dependence of CO(2) uptake on photosynthetic
      electron transport via photosystem I (PSI) was confirmed by experiments with
      electron transport inhibitors, electron donors and acceptors, and a mutant
      lacking PSI activity. CO(2) uptake was drastically inhibited by the uncouplers
      carbonyl cyanide m-chlorophenylhydrazone (CCCP) and ammonia but substantially
      less so by the inhibitors of ATP formation arsenate and N, N,
      dicyclohexylcarbodiimide (DCCD). Thus a DeltamuH(+) generated by photosynthetic
      PSI electron transport apparently serves as the direct source of energy for CO(2)
      uptake. Under low light intensity, the rate of CO(2) uptake by a high-CO(2)
      requiring mutant of Synechococcus sp. PCC7942, at a CO(2) concentration below its
      threshold for CO(2) fixation, was higher than that of the wild type. At
      saturating light intensity, net CO(2) uptake was similar in the wild type and in
      the mutant IL-3 suggesting common limitation by the rate of conversion of CO(2)
      to HCO3(-). These findings are consistent with a model postulating that electron
      transport-dependent formation of alkaline domains on the thylakoid membrane
      energizes intracellular conversion of CO(2) to HCO3(-).

PMID- 11297563
TI  - H2O2-mediated cross-linking between lactoperoxidase and myoglobin: elucidation of
      protein-protein radical transfer reactions.
AB  - The H(2)O(2)-dependent reaction of lactoperoxidase (LPO) with sperm whale
      myoglobin (SwMb) or horse myoglobin (HoMb) produces LPO-Mb cross-linked species,
      in addition to LPO and SwMb homodimers. The HoMb products are a LPO(HoMb) dimer
      and LPO(HoMb)(2) trimer. Dityrosine cross-links are shown by their fluorescence
      to be present in the oligomeric products. Addition of H(2)O(2) to myoglobin (Mb),
      followed by catalase to quench excess H(2)O(2) before the addition of LPO, still
      yields LPO cross-linked products. LPO oligomerization therefore requires radical
      transfer from Mb to LPO. In contrast to native LPO, recombinant LPO undergoes
      little self-dimerization in the absence of Mb but occurs normally in its
      presence. Simultaneous addition of 3,5-dibromo-4-nitrosobenzenesulfonic acid
      (DBNBS) and LPO to activated Mb produces a spin-trapped radical electron
      paramagnetic resonance signal located primarily on LPO, confirming the radical
      transfer. Mutation of Tyr-103 or Tyr-151 in SwMb decreased cross-linking with
      LPO, but mutation of Tyr-146, Trp-7, or Trp-14 did not. However, because DBNBS
      trapped LPO radicals were observed with all the mutants, DBNBS traps LPO radicals
      other than those involved in protein oligomerization. The results clearly
      establish that radical transfer occurs from Mb to LPO and suggest that
      intermolecularly transferred radicals may reside on residues other than those
      that are generated by intramolecular reactions.

PMID- 11297565
TI  - Clinical review 126: Roles and novel regimens of luteinizing hormone and follicle
      stimulating hormone in ovulation induction.
AB  - Although FSH is universally recognized as the key driver of ovarian follicle
      growth and maturation, the role of LH in these processes is more controversial.
      LH acts on theca cells to induce androgen substrate for estrogen conversion by
      the aromatase system; furthermore, LH can affect granulosa cell function starting
      in the mid- follicular phase, when these cells express LH receptors. The capacity
      of LH to stimulate granulosa cells in larger follicles (>10 mm diameter) may be
      the critical mechanism involved in the selection of the dominant follicle in the
      normal menstrual cycle. Furthermore, the addition of LH activity can shorten and
      optimize FSH ovulation induction and reduce the development of smaller
      preovulatory ovarian follicles that are associated with the severe complications
      of this procedure. Novel mixed gonadotropin administration regimens that
      incorporate graded amounts of LH and FSH activity may improve efficacy, safety,
      and cost of ovulation induction, particularly in the area of assisted
      reproduction.

PMID- 11297564
TI  - Na(+)-dependent pH regulation by the amitochondriate protozoan parasite Giardia
      intestinalis.
AB  - Giardia intestinalis is a pathogenic fermentative parasite, which inhabits the
      gastrointestinal tract of animals and humans. G. intestinalis trophozoites are
      exposed to acidic fluctuations in vivo and must also cope with acidic metabolic
      endproducts. In this study, a combination of independent techniques ((31)P NMR
      spectroscopy, distribution of the weak acid pH marker 5,5-dimethyl-2,4
      oxazolidinedione (DMO) and the fluorescent pH indicator 2',7'-bis (carboxyethyl)
      5,6-carboxyfluorescein (BCECF)) were used to show that G. intestinalis
      trophozoites exposed to an extracellular pH range of 6.0--7.5 maintain their
      cytosolic pH (pH(i)) within the range 6.7--7.1. Maintenance of the resting pH(i)
      was Na(+)-dependent but unaffected by amiloride (or analogs thereof). Recovery of
      pH(i) from an intracellular acidosis was also Na(+)-dependent, with the rate of
      recovery varying with the extracellular Na(+) concentration in a saturable manner
      (K(m) = 18 mm; V(max) = 10 mm H(+) min(-1)). The recovery of pH(i) from an acid
      load was inhibited by amiloride but unaffected by a number of its analogs. The
      postulated involvement of one or more Na(+)/H(+) exchanger(s) in the regulation
      of pH(i) in G. intestinalis is discussed.

PMID- 11297566
TI  - Clinical review 127: Obesity as a neuroendocrine disease: lessons to be learned
      from proopiomelanocortin and melanocortin receptor mutations in mice and men.

PMID- 11297567
TI  - Clinical review 128: Current approaches to primary therapy for papillary and
      follicular thyroid cancer.

PMID- 11297568
TI  - Unnatural growth hormone-releasing peptide begets natural ghrelin.

PMID- 11297569
TI  - Pituitary lymphoma presenting as fever of unknown origin.
AB  - An 86-yr-old woman presented with fever of unknown origin. When laboratory
      evaluation revealed partial hypopituitarism, a magnetic resonance imaging scan of
      the head was performed and revealed a sellar mass consistent with a pituitary
      adenoma. Only after other possible etiologies for fever were excluded did she
      undergo transsphenoidal resection of the sellar mass, which proved to be a B-cell
      lymphoma. Primary central nervous system lymphoma of the pituitary region is a
      rare cause of a sellar mass, and this is the first reported case of pituitary
      lymphoma whose presenting manifestation was fever of unknown origin. Several
      disease processes can manifest themselves as fever and a sellar mass, including
      lymphomas. In our case, only surgical biopsy could make a diagnosis and
      distinguish this process from the more common pituitary adenoma.

PMID- 11297570
TI  - Evolving surgical management for patients with pheochromocytoma.

PMID- 11297572
TI  - Of mice and men, recapitulation of Blomstrand's chondrodysplasia.

PMID- 11297571
TI  - Factors associated with perioperative morbidity and mortality in patients with
      pheochromocytoma: analysis of 165 operations at a single center.
AB  - To identify preoperative factors associated with 30-day morbidity and mortality
      after pheochromocytoma surgery, we carried out an external review of the records
      of all patients undergoing pheochromocytoma surgery from 1975 to 1997 at a single
      center. One hundred and forty-seven patients, including 23 with malignant tumors
      at the time of the first operation, underwent 165 operations. Death, resection of
      a neighboring organ, further surgery, secondary transfer to an intensive care
      unit, and any events associated with a surgical stay exceeding 10 days were
      defined as complications. Mortality and morbidity were 4 of 165 (2.4%) and 38 of
      161 (23.6%), respectively. Morbidity included 13 spleen resections and hematomas.
      Spleen complications were not related to tumor location, but were probably due to
      the operative strategy used, a transperitoneal complete abdominal exploration
      including both adrenal glands. Complications were independently associated with
      preoperative systolic blood pressure [odds ratio (OR), 1.14/cm Hg], urinary
      metanephrine excretion (OR, 1.18/10 micromol x day), and with the number of
      operations (repeat vs. first operation OR, 5.36). In conclusion, pheochromocytoma
      resection consistently involves a risk of complications. Spleen damage should be
      prevented by complete preoperative localization studies and an elective or
      laparoscopic surgical approach. Careful blood pressure control should help
      prevent complications. Patients with high secretion tumors and those undergoing
      repeat intervention are at high risk of complications and should be referred to
      centers familiar with pheochromocytoma management.

PMID- 11297573
TI  - Middle-aged men show higher sensitivity of sleep to the arousing effects of
      corticotropin-releasing hormone than young men: clinical implications.
AB  - The prevalence of insomnia associated with emotional stress increases markedly in
      middle-age. Both the top and end hormones of the hypothalamic-pituitary-adrenal
      axis, i.e. CRH and glucocorticoids, stimulate arousal/wakefulness and inhibit
      slow wave (deep) sleep in experimental animals and man. The objective of this
      study was to test the hypothesis that middle-age is characterized by increased
      sensitivity to the sleep-disturbing effects of the hypothalamic-pituitary-adrenal
      axis. We studied 12 healthy middle-aged (45.1 +/- 4.9) and 12 healthy young (22.7
      +/- 2.8) men by monitoring their sleep by polysomnography for 4 consecutive
      nights, including in tandem 1 adaptation and 2 baseline nights and a night during
      which we administered equipotent doses of ovine CRH (1 microg/kg, iv bolus) 10
      min after sleep onset. Analyses included comparisons within and between groups
      using multiple ANOVA and regression analysis. Although both middle-aged and young
      men responded to CRH with similar elevations of ACTH and cortisol, the former had
      significantly more wakefulness and suppression of slow wave sleep compared with
      baseline sleep; in contrast, the latter showed no change. Also, comparison of the
      change in sleep patterns from baseline to the CRH night in the young men to the
      respective change observed in middle-aged men showed that middle-age was
      associated with significantly higher wakefulness and significantly greater
      decrease in slow wave sleep than in young age. We conclude that middle-aged men
      show increased vulnerability of sleep to stress hormones, possibly resulting in
      impairments in the quality of sleep during periods of stress. We suggest that
      changes in sleep physiology associated with middle-age play a significant role in
      the marked increase of prevalence of insomnia in middle-age.

PMID- 11297574
TI  - One year of insulin-like growth factor I treatment does not affect bone density,
      body composition, or psychological measures in postmenopausal women.
AB  - The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH
      IGF-I) axis declines with age, and some of the catabolic changes of aging have
      been attributed to the somatopause. The purpose of this investigation was to
      determine the impact of 1 yr of IGF-I hormone replacement therapy on body
      composition, bone density, and psychological parameters in healthy, nonobese,
      postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 +/- 2.0 yr, 71.8
      +/- 2.8 kg) were randomly assigned to either the self-injection IGF-I (15
      microg/kg twice daily) or placebo group and were studied at baseline, at 6
      months, and at 1 yr of treatment. There were no significant differences between
      the IGF-I and placebo groups in any of the measured variables at baseline.
      Fasting blood IGF-I levels were significantly elevated above baseline values
      (65.6 +/- 11.9 ng/mL) at 6 months (330.0 +/- 52.8) and 12 months (297.7 +/- 40.8)
      in the IGF-I treated group but did not change in the placebo subjects.
      Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I
      treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body
      [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either
      group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or
      percent body fat throughout the treatment intervention. Muscle strength values
      (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density
      lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal
      glucose disposal were not altered by IGF-I treatment, although postmeal insulin
      levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone
      turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects
      who were taking estrogen had significantly lower turnover markers than subjects
      who were not on estrogen at baseline, 6 months, and 12 months. Finally, the
      psychological measures of mood and memory were also not altered by the
      intervention. Despite the initial intent to recruit additional subjects, the
      study was discontinued after 16 subjects completed the protocol, because the
      preliminary analyses above indicated that no changes were occurring in any
      outcome variables, regardless of treatment regimen. Therefore, we conclude that 1
      yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young
      normal values, is not an effective means to alter body composition or blood
      parameters nor improve bone density, strength, mood, or memory in older women.

PMID- 11297575
TI  - Therapy for 6.5-7.5 years with recombinant insulin-like growth factor I in
      children with growth hormone insensitivity syndrome: a clinical research center
      study.
AB  - Eight children with GH insensitivity syndrome were treated with recombinant human
      insulin-like growth factor I (IGF-I) (80--120 microg/kg sc twice daily) for 6.5-
      7.5 yr. We previously reported that height velocity (HV) improved with treatment
      (from mean pretreatment HV of 4.0 cm/yr), to 9.3 cm/yr for the first year and 6.2
      cm/yr for the second year. HV remained slightly below this during the subsequent
      years (mean HV: 5.4, 5.5, 5.2, and 4.8 cm/yr during years 3--6). Mean height SD
      score before therapy was -5.6; and it improved to -4.5, -4.4, and -4.2 after 2,
      4, and 6 yr of therapy, respectively. Treatment was accompanied by gain in body
      weight and fat. Bone age advanced normally in the prepubertal patients, but it
      advanced more rapidly during the latter years of treatment in those patients
      undergoing pubertal changes. The growth of spleen and kidneys (determined by
      ultrasound) was rapid in the first 2--3 yr of therapy. More age- appropriate
      growth ensued, but six patients had a renal length for height more than 2 SD
      above the mean at 6--7 yr of treatment. No major adverse changes in biochemical
      profile were observed. IGF-I-related hypoglycemia occurred early in treatment
      with the younger patients, but this problem abated as treatment was continued.
      IGF-I therapy is effective in promoting statural growth in GH insensitivity
      syndrome patients, but the growth response is neither as intense nor as well
      sustained as the growth response to GH among children with GH deficiency.

PMID- 11297576
TI  - Growth hormone therapy alone or in combination with gonadotropin-releasing
      hormone analog therapy to improve the height deficit in children with congenital
      adrenal hyperplasia.
AB  - Short stature in the adult patient with congenital adrenal hyperplasia (CAH) is
      commonly seen, even among patients in excellent adrenal control during childhood
      and puberty. In this study we examine the effect of GH therapy on height
      prediction in children with both CAH and compromised height prediction.
      Leuprolide acetate, a GnRH analog (GnRHa), was given to patients with evidence of
      early puberty. GH (n = 12) or the combination of GH and GnRHa (n = 8) was
      administered to 20 patients with CAH while they continued therapy with
      glucocorticoids. Each patient in the treatment group was matched according to
      age, sex, bone age, puberty, and type of CAH with another CAH patient treated
      only with glucocorticoid replacement. The match was made at the start of GH
      treatment. Of the 20 patients, 12 have completed 2 yr of therapy. After 1 yr of
      GH or combination GH and GnRHa therapy, the mean growth rate increased from 5 +/-
      1.9 to 7.8 +/- 1.6 cm/yr vs. 5.4 +/- 1.7 to 5 +/- 2 cm/yr in the group not
      receiving GH (P < 0.0001). During the second year of treatment, the mean growth
      rate was 6 +/- 1.6 vs. 4.2 +/- 2.1 cm/yr in the group not receiving GH (P <
      0.001). The height SD score for chronological age in the treatment group at the
      end of 1 and 2 yr of treatment improved significantly more than the nontreatment
      group (P < 0.01). A similar improvement in the height SD score for bone age was
      found in the treatment group after 1 (-1.4 +/- 0.9 vs. -1.7 +/- 0.9; P < 0.0001)
      and 2 yr of therapy (-0.67 +/- 0.68 vs. -1.7 +/- 1.2; P < 0.0004). The mean
      predicted adult height improved from 159 +/- 11 (baseline) to 170 +/- 7.5 cm
      (after 2 yr of therapy) closely approximating target height (173 +/- 8 cm). All
      patients continued the hydrocortisone treatment. In patients with CAH and
      compromised height prediction, treatment with GH or the combination of GH and
      GnRHa results in an improvement of growth rate and height prediction and a
      reduction in height deficit for bone age.

PMID- 11297577
TI  - Effects of growth hormone (GH) administration on homocyst(e)ine levels in men
      with GH deficiency: a randomized controlled trial.
AB  - GH deficiency is associated with increased cardiovascular mortality and early
      manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been
      found to be associated with increased cardiovascular risk. The effect of GH
      replacement on homocyst(e)ine has not been investigated to date. We evaluated the
      effect of GH replacement on fasting homocyst(e)inemia in a group of men with
      adult-onset GH deficiency in a randomized, single blind, placebo-controlled
      trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo
      for 18 months, with dose adjustments made according to serum insulin-like growth
      factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and
      total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry,
      IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months.
      Nutritional assessment, body composition, total T(4), thyroid hormone binding
      index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased
      in the GH-treated group compared with that in the placebo group (net difference, 
      1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047).
      Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate
      (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in
      the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval,
      0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not
      significantly change between groups. Changes in homocyst(e)ine were negatively
      correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I,
      homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast,
      changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12,
      total T(3), C-reactive protein, interleukin-6, or insulin levels. This study
      shows that GH replacement decreases fasting homocyst(e)ine levels compared with
      placebo. This may be one of the mechanisms involved in the putative modulation of
      atherosclerosis and cardiovascular risk by GH replacement.

PMID- 11297578
TI  - Parathyroid hormone-related protein-(1--36) stimulates renal tubular calcium
      reabsorption in normal human volunteers: implications for the pathogenesis of
      humoral hypercalcemia of malignancy.
AB  - All would agree that hypercalcemia occurs among patients with humoral
      hypercalcemia of malignancy (HHM) as a result of osteoclastic bone resorption.
      Some studies suggest that enhanced renal calcium reabsorption, which plays an
      important pathophysiological role in the hypercalcemia occurring in primary
      hyperparathyroidism, is also important pathophysiologically in HHM. Other studies
      have not agreed. In large part, these differences result from the inability to
      accurately assess creatinine and calcium clearance in critically ill subjects
      with HHM. To circumvent these issues, we have developed steady state 48-h PTH
      related protein (PTHrP) infusion and 8-h hypercalcemic calcium clamp protocols.
      These techniques allow assessment of the effects of steady state PTHrP and
      calcium infusions in normal healthy volunteers in a setting in which renal
      function is stable and measurable and in which the filtered load of calcium can
      be matched in PTHrP- and calcium-infused subjects. Normal subjects were infused
      with saline (placebo), PTHrP, or calcium. Subjects receiving PTHrP, as expected,
      displayed mild hypercalcemia (10.2 mg/dL), suppression of endogenous PTH-(1--84),
      and phosphaturia. Subjects receiving the hypercalcemic calcium clamp displayed
      indistinguishable degrees of hypercalcemia and PTH suppression. Despite their
      matched degrees of hypercalcemia and PTH suppression, the two groups differed
      importantly with regard to fractional calcium excretion (FECa). The hypercalcemic
      calcium clamp group was markedly hypercalciuric (FECa averaged 6.5%), whereas
      FECa in the PTHrP-infused subjects was approximately 50% lower (between 2.5-
      3.7%), and no different from that in the normal controls, which ranged from 1.5-
      3.0%. These studies demonstrate that PTHrP is able to stimulate renal calcium
      reabsorption in healthy volunteers. These studies suggest that PTHrP-induced
      renal calcium reabsorption, in concert with the well established acceleration of
      osteoclastic bone resorption, contributes in a significant way to the
      hypercalcemia observed in patients with HHM.

PMID- 11297579
TI  - The importance of autosomal genes in Kallmann syndrome: genotype-phenotype
      correlations and neuroendocrine characteristics.
AB  - Kallmann syndrome (KS) consists of congenital, isolated, idiopathic
      hypogonadotropic hypogonadism (IHH) and anosmia. The gene responsible for the X
      linked form of KS, KAL, encodes a protein, anosmin, that plays a key role in the
      migration of GnRH neurons and olfactory nerves to the hypothalamus. In addition
      to X-linked pedigrees, autosomal dominant and recessive kindreds with KS have
      been reported. The relative importance of these autosomal vs. X-linked genes in
      producing KS, and the frequency of KAL mutations, are currently unknown because
      these are rare disorders and large series are unusual. We examined 101
      individuals with IHH (+/- anosmia) and their families to determine their modes of
      inheritance, incidence of mutations in the coding sequence of KAL, genotype
      phenotype correlations, and [in a subset (n = 38)] their neuroendocrine
      phenotype. Of the 101 patients, 59 had true KS (IHH + anosmia/hyposmia); whereas,
      in the remaining 42, no anosmia was evident in the patients or their families. Of
      the 59 KS patients, 21 were familial, whereas 38 were sporadic cases. Mutations
      in the coding sequence of KAL were identified in only 3 of 21 familial cases
      (14%) and 4 of 38 (11%) of the sporadic cases. Of the X-linked cases confirmed by
      mutational analysis, only 1 of 3 pedigrees appeared X-linked by inspection
      whereas the other 2 contained only affected brothers. Female members of known KAL
      mutation families (n = 3) exhibited no reproductive phenotype and were not
      anosmic, whereas families with anosmic women (n = 3) were not found to carry
      mutations in KAL. Mutations were uniformly absent in nonanosmic IHH probands (n =
      42), as well as in families with both anosmic and nonanosmic members (n = 2).
      Overall, 4 novel mutations were identified (C172R, R191x, R457x, and delC@L600).
      With respect to neuroendocrine phenotype, KS men with documented KAL mutations (n
      = 8) had completely apulsatile LH secretion, whereas those with autosomal modes
      of inheritance demonstrated a more variable spectrum with evidence of enfeebled
      (but present) GnRH-induced LH pulses. Our conclusions are: 1) Confirmed mutations
      in the coding sequence of the KAL gene occur in the minority of KS cases, i.e.
      only 14% of familial and 11% of sporadic cases; 2) The majority of familial (and
      presumably sporadic) cases of KS are caused by defects in at least two autosomal
      genes that are currently unknown; 3) Obligate female carriers in families with
      KAL mutations have no discernible phenotype; 4) KAL mutations are uniformly
      absent in patients with either normosmic IHH or in families with both anosmic and
      nonanosmic individuals; and 5) Patients with KAL mutations have apulsatile LH
      secretion consistent with a complete absence of GnRH migration of GnRH cells into
      the hypothalamus, whereas evidence of present (but enfeebled) GnRH-induced LH
      pulses may be present in autosomal KS cases. Taken together, these findings
      suggest that autosomal genes account for the majority of familial cases of KS,
      and that unique neuroendocrine phenotypes consistent with some GnRH neuronal
      migration may exist in these patients.

PMID- 11297580
TI  - Novel assay for determination of androgen bioactivity in human serum.
AB  - We have developed a mammalian cell (COS-1) bioassay, which can measure androgen
      bioactivity directly from a small amount (10 microL) of human serum. The
      recombinant assay is based on androgen-dependent interaction between the ligand
      binding domain and the N-terminal region of the androgen receptor (AR), which
      were fused to Gal4 DNA-binding domain of Saccharomyces cerevisiae and
      transcriptional activation domain of herpes simplex VP16 protein, respectively.
      The interaction is amplified by coexpression of AR-interacting protein 3 in the
      cells. The reporter plasmid contains 5 Gal4-binding sites upstream of the
      luciferase gene; luciferase activity in cell lysates is derived from androgen
      bioactivity in human serum. Saturating concentration of testosterone in FCS
      induced more than 700-fold induction in relative luciferase activity. The
      sensitivity was less than 1.0 nmol/L testosterone in FCS. The intra- and
      interassay coefficients of variation were 8.3% and 21%, respectively. Interaction
      between the AR termini was blocked by nonsteroidal antiandrogens, and the assay
      exhibited minimal cross-reactivity with 17 beta-estradiol. Serum androgen
      bioactivity was studied in 23 boys (13.9--16.8 yr old) with constitutional delay
      of puberty and in 9 prepubertal boys with cryptorchidism (1.0--6.4 yr old).
      Androgen bioactivity was detectable in 15 boys with constitutional delay of
      puberty and in all boys with cryptorchidism during treatment with human CG
      (range, 1.0-14.5 nmol/L testosterone equivalents). Serum androgen bioactivity
      measured by the bioassay correlated strongly with serum testosterone
      concentration (r = 0.93, P < 0.0001, n = 22) but not to 5 alpha
      dihydrotestosterone, dehydroepiandrosterone, or androstenedione levels. We
      conclude that our novel bioassay enables quantitation of mammalian cell response
      to bioactive androgens in human serum, even in pediatric patients with relatively
      low androgen levels.

PMID- 11297581
TI  - Combined pituitary hormone deficiency caused by compound heterozygosity for two
      novel mutations in the POU domain of the Pit1/POU1F1 gene.
AB  - The POU homeodomain containing transcriptional activator POU1F1, formerly called
      Pit1 or GHF-1, is required for the embryological determination and postnatal
      secretory function of the GH-, PRL-, and TSH-producing cells in the anterior
      pituitary. Several mutations in the gene encoding POU1F1 have been described,
      resulting in a syndrome of combined pituitary hormone deficiency involving these
      three hormones. Most of the patients with this phenotype have either a dominant
      negative mutation in codon 271 (R271W) or are homozygous for a recessive mutation
      in the POU1F1 gene; to date only one case has been reported with compound
      heterozygosity for two point mutations. Here, we describe a boy with severe
      deficiencies of GH, PRL, and TSH who had compound heterozygosity for two novel
      point mutations in the POU1F1 gene: a 1-bp deletion frameshift mutation
      (747delA), the first one described to date in this gene, which leads to a
      nonfunctional truncated protein lacking the entire DNA recognition helix of the
      POU homeodomain, and a missense mutation in the C-terminal end of the fourth
      alpha-helix of the POU-specific domain (W193R),which causes a 500-fold reduction
      in the ability to bind to DNA and activate transcription.

PMID- 11297582
TI  - Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of
      growth hormone and insulin-like growth factor I levels on cardiac performance.
AB  - Acromegalic patients are considered to be exposed to a doubled mortality rate,
      mostly for cardiovascular diseases. This open prospective study was designed to
      evaluate whether the impairment of cardiac performance could be reversed by the
      long-term suppression of GH and insulin-like growth factor I (IGF-I) levels.
      Eighteen patients with active acromegaly were studied before and 5 yr after
      surgery, followed by sc octreotide in 11 patients. Disease control (GH levels <
      or =1 microg/L after glucose load or < or =2.5 microg/L after fasting,
      respectively, together with normalized IGF-I levels for age) was achieved in
      seven patients after surgery and in six patients after 0.3--0.6 mg/day sc
      octreotide. Five patients were not controlled during the 5-yr follow-up. Cardiac
      performance at rest and at peak exercise was assessed by equilibrium radionuclide
      angiography at study entry and 5 yr after surgery alone or plus octreotide.
      Thirty-six sex- and age-matched healthy subjects served as controls. At study
      entry, patients had a lower left ventricular ejection fraction (LVEF) at peak
      exercise and LVEF exercise-induced changes, exercise duration, and capacity than
      controls (P < 0.001). After 5 yr of treatment, a significant decrease of resting
      heart rate (P = 0.03) and a significant increase of LVEF at peak exercise (P =
      0.003) was found in patients achieving disease control. LVEF response at peak
      exercise worsened in none of the patients with controlled disease and in three
      patients with uncontrolled disease (60%) (chi(2) = 5.5; P = 0.02). Diastolic
      filling, exercise duration, and workload did not significantly change during the
      5-yr follow-up. No difference was found between patients controlled by surgery
      alone or by surgery plus octreotide. This 5-yr prospective study demonstrated
      that the LVEF response at peak exercise improved in all patients achieving
      disease control, while it was worsened in 60% of uncontrolled ones. These results
      strengthen the need of a stable suppression of GH and IGF-I hypersecretion to
      restore a normal cardiac performance in acromegaly.

PMID- 11297583
TI  - Prostate-specific antigen and human glandular kallikrein 2 are markedly elevated
      in urine of patients with polycystic ovary syndrome.
AB  - Prostate-specific antigen (PSA) is a well-established tumor marker of prostatic
      adenocarcinoma. Human glandular kallikrein 2 (hK2), another serine protease
      closely related to PSA, is also gaining ground as a promising diagnostic tool in
      prostate cancer. The expression of these 2 proteases is known to be regulated by
      androgens and progestins in hormonally responsive tissues, such as the male
      prostate and the female breast. Previously, we have shown that serum PSA levels
      in normal women are very low but still detectable by ultrasensitive PSA
      immunoassays. We have also demonstrated that some women with hyperandrogenic
      syndromes have elevated serum PSA levels. In this study, we have measured urinary
      PSA and urinary hK2 levels in 35 polycystic ovary syndrome (PCOS) patients and
      compared them to those of 41 age-matched controls. We found that urinary PSA
      levels were significantly higher (P < 0.0001) in PCOS patients (mean +/- SE = 820
      +/- 344 ng/L) than in the controls (mean +/- SE = 4.3 +/- 1.8 ng/L). Similarly,
      the difference between urinary hK2 of patients (mean +/- SE = 8.2 +/- 3.1 ng/L)
      and controls (0.5 +/- 0.3 ng/L) was also significant (P < 0.001). A weak
      correlation was observed between urinary PSA and serum 3 alpha-androstanediol
      glucuronide (r(s) = 0.42, P = 0.03) as well as between urinary PSA and serum
      testosterone (r(s) = 0.40, P = 0.04). The results of this study indicate that
      urinary PSA, and possibly urinary hK2, are promising markers of hyperandrogenism
      in females suffering from PCOS.

PMID- 11297584
TI  - Basal, pulsatile, entropic, and 24-hour rhythmic features of secondary
      hyperprolactinemia due to functional pituitary stalk disconnection mimic tumoral
      (primary) hyperprolactinemia.
AB  - Under physiological conditions, PRL secretion is regulated precisely by various
      stimulating and inhibiting factors. Hyperprolactinemia may arise as a primary
      consequence of a PRL-secreting pituitary adenoma. Secondary hyperprolactinemia
      (SH) may emerge in patients with hypothalamic disease, hypophyseal stalk
      compression, or suprasellar extension of a (nonlactotrope) pituitary adenoma. The
      latter may reflect diminished delivery of dopamine or other inhibitory factors to
      normal lactotropes. We hypothesized that diurnal and ultradian rhythms of PRL
      secretion would differ in secondary (e.g. hypothalamic) and primary (e.g. tumoral
      states) hyperprolactinemia (PH), assuming that the underlying pathophysiologies
      differ. To test this clinical postulate, we investigated the patterns of 24-h PRL
      release in eight patients with SH associated with functional hypothalamo
      pituitary disconnection and in eight patients with PH attributable to
      microprolactinoma. Data in each group were compared with values in healthy gender
      matched controls. PRL time series were obtained by repetitive 10-min blood
      sampling, followed by high- precision immunofluorometric assay. PRL concentration
      profiles were analyzed by the complementary tools of model-free discrete peak
      detection, waveform-independent deconvolution analysis, cosinor regression, and
      the approximate entropy metric to quantitate pulsatile, basal, 24-h rhythmic, and
      pattern-dependent (entropic) PRL secretion. Patients with tumoral
      hyperprolactinemia (PH) showed a 2-fold higher 24-h mean serum PRL concentration
      than patients with SH (62 +/- 13 microg /L vs. 30 +/- 6.9 microg/L, respectively,
      P = 0.029). Estimated PRL pulse frequency (events/24 h) was similar in the two
      patient groups (18.5 +/- 0.7 vs. 17.6 +/- 0.8; P = 0.395) but elevated over that
      in euprolactinemic controls (P < 0.0001 for both). Deconvolution analysis
      disclosed a mean daily PRL secretion rate of 790 +/- 170 microg in PH patients
      vs. 380 +/- 85 microg in SH patients (P = 0.030). Nonpulsatile PRL secretion
      comprised nearly 70% of total secretion in both patient groups and 50% in
      controls (P < 0.0001). Cosinor analysis revealed similar acrophases in all three
      study cohorts. The mean skewness of the statistical distribution of the
      individual PRL sample secretory rates was reduced, compared with controls (P < 10
      (-5) for each), but equivalent in SH and PH patients (0.83 +/- 0.12 vs. 0.78 +/-
      0.08, respectively), denoting a loss of the normal spectrum of low- and higher
      amplitude secretion rates. Approximate entropy, a regularity statistic, was
      markedly elevated in both patient groups over controls (P < 10 (-6) for each) and
      was slightly higher in PH patients than in SH patients (1.639 +/- 0.029 vs. 1.482
      +/- 0.067, P = 0.048). In summary, patterns of PRL secretion in PH and SH states
      exhibit an equivalently increased frequency of PRL pulses, a comparably marked
      rise in nonpulsatile (basal) PRL secretion. Despite overlap, the regularity of
      PRL release patterns is disrupted even more profoundly in PH (tumoral), compared
      with SH. Assuming that the orderliness of serial PRL output monitors normal
      integration within a feedback-controlled neurohormone axis, then the more
      disorderly patterns of tumoral PRL secretion point to greater regulatory
      disruption in PH. The latter may reflect abnormal secretory behavior associated
      with lactotrope neoplastic transformation and/or isolation of the tumor cell mass
      from normal hypothalamic controls.

PMID- 11297585
TI  - Survival and therapeutic modalities in patients with bone metastases of
      differentiated thyroid carcinomas.
AB  - Data for patients with bone metastases (BMs) of differentiated thyroid carcinoma
      (DTC) were retrospectively studied to identify factors associated with survival.
      We especially studied the impact of therapies. Among the 1977 patients followed
      for DTC in our department from 1958 to 1999, 109 (77 females and 32 males; age
      range, 20--87 yr) presented BMS: All patients except 1 underwent total
      thyroidectomy, followed by radioiodine therapy (> or =3.7 gigabecquerels) in 95
      cases. Survival rates at 5 and 10 yr were 41% and 15%, respectively. Univariate
      analyses indicated that a young age at BM discovery (P < 0.005) and the discovery
      of BM as a revealing symptom of DTC (P < 0.05) were features significantly
      associated with improved survival as well as radioiodine therapy (P < 10(-4)) and
      BM complete surgery (P < 0.02). Using multivariate analysis, the detection of BMs
      as a revealing symptom of thyroid carcinoma (P < 0.0005), the absence of
      metastasis appearance in other organs than bones during the follow-up (P < 0.03),
      the cumulative dose of radioiodine therapy (P < 0.0001), and complete BM surgery
      in young patients (P < 0.04) appeared as independent prognostic features
      associated with an improved survival.

PMID- 11297586
TI  - Relationship between the morphological evaluation of the pituitary and the growth
      hormone (GH) response to GH-releasing hormone Plus arginine in children and
      adults with congenital hypopituitarism.
AB  - The relationship between the hypothalamus-pituitary morphology and the
      somatotroph responsiveness to maximal provocative tests exploring the GH
      releasable pool is still unclear. We evaluated the GH-releasing effect of GHRH
      plus arginine (GHRH plus Arg) in 36 patients with congenital GH deficiency (GHD)
      according to their pituitary magnetic resonance imaging findings, consisting of
      anterior pituitary hypoplasia, stalk agenesis (neural and or vascular component),
      and posterior pituitary ectopia. Seventeen children (12 boys and 5 girls, aged 1-
      5.2 yr) were evaluated at the time of diagnosis of GHD (mean age, 3.6 +/- 1.4
      yr), and 19 adults (13 males and 6 females, aged 15.9-28.6 yr) with childhood
      onset GHD were reevaluated after completion of GH treatment (at least 6 months of
      withdrawal) at a mean age of 20.5 +/- 3.5 yr. Eleven children had isolated GHD,
      and 6 had multiple pituitary hormone deficiency (MPHD) whereas 7 adults had
      isolated GHD, and 12 had MPHD. A residual vascular component of the pituitary
      stalk was visualized in 7 children and 7 adults with isolated GHD, whereas
      magnetic resonance imaging showed complete pituitary stalk agenesis (both
      vascular and neural components) in 10 children and 10 adults, including 16 with
      MPHD (6 children) and 4 children with isolated GHD. In the children, the median
      peak GH response to GHRH plus Arg (7.6 microg/L; range, 2.4--40.2 microg/L) was
      significantly higher than that in the adults (1.8 microg/L; range, 0.8--37.4
      microg/L; P = 0.0039); it was also significantly higher in the isolated GHD
      patients (18 microg/L; range, 3.3--40.2 microg/L) than in those with MPHD (1.9
      microg/L; range, 0.8--7.6 microg/L; P = 0.00004). In the patients with residual
      vascular component of the pituitary stalk the median peak GH responses to GHRH
      plus Arg (19.1 microg/L; range, 1.6--40.2 microg/L) was significantly higher than
      that in patients with complete pituitary stalk agenesis (2.2 microg/L; range, 0.8
      -8.8 microg/L; P = 0.00005). There was a trend toward a decrease with age in peak
      GH response to GHRH plus ARG: Mean serum insulin-like growth factor I (IGF-I)
      levels were 36 +/- 7.1 microg/L in the children and 63.5 +/- 22.6 microg/L in the
      adults (P = 0.0001). The mean IGF-I level did not differ between the children
      with (35.7 +/- 4.8 microg/L) and those without (36.3 +/- 8.7 microg/L) the
      pituitary stalk; it was much higher in the adults with residual vascular
      pituitary stalk (81.1 +/- 17.7 microg/L) than in those with complete pituitary
      stalk agenesis (47.7 +/- 12.5 microg/L; P = 0.0002). The IGF-I level was 36.1 +/-
      6.7 microg/L in the isolated GHD children and 36 +/- 8.6 microg/L in those with
      MPHD; levels were 82.1 +/- 19.4 and 52.7 +/- 16.8 microg/L respectively, in the
      adults (P = 0.003). In this study we have confirmed that the partial integrity of
      the hypothalamic pituitary connections is essential for GHRH plus Arg to express
      its GH-releasing activity and have shown that this provocative test is able to
      stimulate GH secretion to a greater extent in those patients with GHD, but with a
      residual vascular component of the pituitary stalk. This test is reliable in the
      diagnosis of congenital hypopituitarism in both children and adults when
      associated with complete pituitary stalk agenesis and MPHD. In younger children
      with congenital GHD but less severe impairment of the pituitary stalk the GH
      response to GHRH plus Arg may be within the normal range; deterioration of
      pituitary GH reserve with a GH response of less than 10 microg/L after 20 yr of
      age makes this test very sensitive in the diagnosis of adult GHD.

PMID- 11297587
TI  - Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin
      releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism.
AB  - Mutations in the GnRH receptor (GNRHR) have been described as a cause of
      reproductive failure in a subset of patients with idiopathic hypogonadotropic
      hypogonadism (IHH). Given the apparent rarity of these mutations, we set out to
      determine the frequency and distribution of GNRHR mutations in a heterogeneous
      population of patients with IHH who were well characterized with respect to
      diagnosis, phenotype, and mode of inheritance and to define their distribution
      within the receptor protein. One hundred and eight probands with IHH were
      screened for mutations in the coding sequence of GNRHR. Forty-eight of the 108
      patients had a normal sense of smell, whereas the remaining 60 had anosmia or
      hyposmia (Kallmann syndrome). Exon segments in the GNRHR were screened for
      mutations using temperature gradient gel electrophoresis, and all mutations were
      confirmed by direct sequencing. Five unrelated probands (3 men and 2 women), all
      normosmic, were documented to have changes in the coding sequence of the GNRHR.
      Two of these probands were from a subgroup of 5 kindreds consistent with a
      recessive mode of inheritance, establishing a GNRHR mutation frequency of 2 of 5
      (40%) in patients with normosmic, autosomal recessive IHH. The remaining 3
      probands with GNRHR mutations were from a subgroup of 18 patients without
      evidence of familial involvement, indicating a prevalence of 3 of 18 (16.7%) in
      patients with sporadic IHH and a normal sense of smell. Among the five
      individuals bearing GNRHR mutations, a broad spectrum of phenotypes was noted,
      including testicular sizes in the male that varied from prepubertal to the normal
      adult male range. Three probands had compound heterozygous mutations, and two had
      homozygous mutations. Of the eight DNA sequence changes identified, four were
      novel: Thr(32)Ile, Cys(200)Tyr, Leu(266)Arg, and Cys(279)TYR: COS-7 cells
      transiently transfected with complementary DNAs encoding the human GNRHR
      containing each of these four novel mutations failed to respond to GnRH agonist
      stimulation. We conclude that 1) the spectrum of phenotypes in patients with
      GNRHR mutations is much broader than originally anticipated; 2) the frequency of
      GNRHR mutations may be more common than previously appreciated in familial cases
      of normosmic IHH and infrequent in sporadic cases; and 3) functional mutations of
      the GNRHR are distributed widely throughout the protein.

PMID- 11297588
TI  - The rise of estradiol and inhibin B after acute stimulation with follicle
      stimulating hormone predict the follicle cohort size in women with polycystic
      ovary syndrome, regularly menstruating women with polycystic ovaries, and
      regularly menstruating women with normal ovaries.
AB  - Polycystic ovaries contain a larger number of antral follicles than control
      ovaries. The aim of this study was to test whether the increase in estradiol
      (E(2)) and inhibin B after stimulation with 300 IU recombinant FSH in the early
      follicular phase and the ovarian volume can predict the size of the follicle
      cohort in polycystic ovary syndrome (PCOS) patients (n = 10), patients with
      polycystic ovaries detected by ultrasound but with regular menstrual cycles (PCO;
      n = 10), and regularly menstruating patients with normal ovaries (n = 10). The
      follicle cohort size was measured as the FSH-sensitive follicles growing during a
      standardized in vitro fertilization stimulation. Linear regression analysis
      showed that the slopes of the regression lines of the E(2) increment and the
      inhibin B increment in relation to the number of follicles were not significantly
      different among the three groups, meaning that an increased sensitivity for FSH
      of the granulosa cells of polycystic ovaries was not found. For the total group
      (n = 30) we calculated that an E(2) increment of 100 pmol/L predicts 5.5
      follicles (95% confidence interval, 2.8--8.2; r = 0.617; P < 0.001), and an
      inhibin B increment of 100 ng/L predicts 6.2 follicles (95% confidence interval,
      3.5--9.0; r = 0.665; P < 0.001). The ovarian volume could not be used in a
      prediction model because the association with the number of follicles was
      different in the PCO group compared with the PCOS and the control group. Women
      with PCO and women with PCOS both had a follicle cohort twice as big as the
      cohort in control women (P < 0.01). The differences in menstrual cycle pattern
      between the PCO and PCOS groups cannot be explained by differences in cohort
      size.

PMID- 11297589
TI  - Laparoscopic adrenalectomy for adrenocorticotropin-dependent Cushing's syndrome.
AB  - Bilateral adrenalectomy is indicated for the treatment of ACTH-dependent
      Cushing's syndrome when the tumorous source of ACTH hypersecretion cannot be
      identified or removed. Potential advantages of laparoscopic over open
      adrenalectomy include shorter hospitalization, decreased requirement for
      postoperative analgesia, and decreased postoperative morbidity due to incisional
      complications. Bilateral laparoscopic adrenalectomy performed for the treatment
      of ACTH-dependent Cushing's syndrome was attempted in 19 patients at our
      institution between 1995 and 1998. Conversion to an open procedure was required
      in three patients. All patients who underwent bilateral laparoscopic
      adrenalectomy were subsequently followed to assess the outcome of this
      intervention. Twelve patients with pituitary-dependent Cushing's syndrome and
      four with ectopic ACTH syndrome underwent successful bilateral laparoscopic
      adrenalectomy. All patients experienced resolution of the signs and symptoms
      (e.g. proximal myopathy, hirsutism, and emotional lability) of Cushing's syndrome
      as well as weight loss, improved glucose tolerance, and improved control of blood
      pressure. No residual cortisol secretion was detected in the patients. Bilateral
      laparoscopic adrenalectomy is a safe and effective treatment for Cushing's
      syndrome when the ACTH-secreting neoplasm cannot be removed.

PMID- 11297590
TI  - Hyperplastic pituitary gland, high serum glycoprotein hormone alpha-subunit, and
      variable circulating thyrotropin (TSH) levels as hallmark of central
      hypothyroidism due to mutations of the TSH beta gene.
AB  - Inheritable isolated central hypothyroidism (ICH) due to mutations of TSH beta
      gene has been reported in few patients. For this reason the diagnostic criteria
      are vague. The disorder is usually characterized by undetectable TSH levels,
      although low/normal serum TSH, depending on TSH measurement methods, has been
      documented in some patients. Here we report an Egyptian girl with ICH due to a
      novel nonsense mutation of the TSH beta gene (Q49X). She was referred at 75 days
      of age for severe clinical signs of hypothyroidism, whose central origin was
      documented by normal serum TSH, low free T(4) and free T(3) levels, impaired TSH
      response to TRH, absence of (99)Tc thyroidal uptake, and antithyroid
      autoantibodies. Ultrasound revealed a hypoplastic thyroid, whereas magnetic
      resonance imaging showed a hyperplastic pituitary. All other pituitary hormones,
      including PRL, were normally secreted. A diagnosis of idiopathic ICH was made,
      and substitutive L-T(4) treatment was started at 81 days of age. At the age of 7
      yr the patient had normal thyroid hormone levels, but was severely mentally
      retarded. Interestingly, the sella computed tomography scan had completely
      normalized. At 8 yr of age the patient was reinvestigated after 6-week L-T(4)
      withdrawal. TSH values were highly variable depending on the measurement method
      used, whereas extremely high levels of circulating free glycoprotein alpha
      subunit were recorded. Despite the fact that mutant TSH beta lacks 60% of the C
      terminal amino acid sequence, it forms with the alpha-subunit a heterodimer with
      preserved immunoreactivity in some TSH measurement methods, but the mutant
      heterodimer is completely devoid of bioactivity. In conclusion, high circulating
      free glycoprotein alpha-subunit levels, variable TSH levels, and, possibly,
      hyperplastic pituitary gland are the hallmark of ICH due to mutations of the TSH
      beta gene.

PMID- 11297591
TI  - C-peptide and glucagon profiles in minority children with type 2 diabetes
      mellitus.
AB  - The present study was conducted to determine the extent of insulin deficiency and
      glucagon excess in the hyperglycemia of type 2 diabetes in children. The
      incidence of type 2 diabetes mellitus in children and adolescents has increased
      substantially over the past several years. Because insulin and glucagon action
      both regulate blood glucose concentration, we studied their responses to mixed
      meals in children with type 2 diabetes. Subjects were 24 patients with type 2
      diabetes compared with 24 controls, aged 9--20 yr (predominantly African
      Americans), matched for body mass index and sexual maturation. All of those with
      diabetes were negative for antibodies to glutamic acid decarboxylase. Plasma
      glucose, glucagon, and serum C-peptide concentrations were measured at 0, 30, 60,
      90, and 120 min after a mixed liquid meal (Sustacal) ingestion (7 mL/kg body
      weight; maximum, 360 mL). The area under the curve (AUC) was calculated by
      trapezoidal estimation. The incremental C-peptide (Delta CP) in response to the
      mixed meal was calculated (peak -- fasting C-peptide). The plasma glucose AUC was
      significantly greater in patients than in controls (mean +/- SEM, 1231 +/- 138
      vs. 591 +/- 13 mmol/L x min; P < 0.001). The Delta CP was significantly lower in
      those with diabetes than in controls (1168 +/- 162 vs. 1814 +/- 222 pmol/L; P <
      0.02). Glucagon responses did not differ between the two groups. Hyperglycemia is
      known to inhibit glucagon secretion. Therefore, our patients with substantial
      hyperglycemia would be expected to have decreased glucagon responses compared
      with controls and are thus relatively hyperglucagonemic. Patients were divided
      into poorly and well controlled subgroups (glycosylated hemoglobin A(1c), > or
      =7.2% and <7.2%, respectively). There were no significant differences in the
      Delta CP and glucagon responses between these two subgroups. We next analyzed the
      data in terms of duration of diabetes (long term, > or =1 yr; short term, <1 yr).
      The CP was significantly lower in long- vs. short-term patients (768 +/- 232 vs.
      1407 +/- 199 pmol/L; P < 0.05). The plasma glucagon AUC was significantly higher
      in the long- vs. short-term patients (9029 +/- 976 vs. 6074 +/- 291 ng/L x min; P
      < 0.001). Hemoglobin A(1c) did not differ between long- vs. short-term patients.
      Our results indicate that relative hypoinsulinemia and hyperglucagonemia
      represent the pancreatic beta- and alpha-cell dysfunctions in children with type
      2 diabetes. The severity of both beta- and alpha-cell dysfunctions appears to be
      determined by the duration of diabetes.

PMID- 11297592
TI  - Combined treatment with corticosteroids and moclobemide favors normalization of
      hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple
      sclerosis: a randomized, double blind trial.
AB  - Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple
      sclerosis (MS), an autoimmune inflammatory disease of the central nervous system,
      is presumably due to diminished corticosteroid receptor function. It probably
      influences the immune response, but its clinical significance is not clear.
      Similar HPA dysregulation occurs in depression and is reversible with successful
      antidepressant treatment. We conducted a double blind, placebo-controlled trial
      to evaluate the neuroendocrine effect of cotreatment with the antidepressant
      moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with
      definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded
      Disability Status Scale score of neurological impairment, 2.0--6.5) in acute
      relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible
      monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral
      fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were
      evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30,
      and 75. At baseline, the HPA axis was mildly activated, comparably for treatment
      groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary
      units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group;
      mean +/- SEM]. In a group of healthy controls with comparable demographic
      characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment
      resulted in normalization of the HPA axis response, whereas the HPA system
      hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/-
      22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change
      in Expanded Disability Status Scale was comparable for both groups. Although
      corticosteroids alone had no effect on the HPA response using the dexamethasone
      CRH test, treatment with moclobemide combined with corticosteroids favors
      normalization of the HPA response in relapsing-remitting MS.

PMID- 11297593
TI  - Cellular localization of orexin receptors in human pituitary.
AB  - Orexins-A and -B are hypothalamic peptides derived from a precursor called prepro
      orexin and relationated with the stimulation of food intake. They act on G
      protein receptors named orexin receptor 1 (OX(1)R) and orexin receptor 2
      (OX(2)R), respectively. In the present study, we used RT-PCR and
      immunohistochemical techniques to detect the presence of OX(1)R and OX(2)R in
      human pituitary. A band of the expected size for both OX(1)R and OX(2)R was shown
      in human pituitary by RT-PCR. The cellular localization of OX(1)R and OX(2)R was
      carried out using histological techniques. By consecutive sections we
      demonstrated that OX(1)R was present in acidophil, diffusely distributed cells,
      which represent the half of the total adenohypophysis cell population. As was
      expected, these cells were shown to coexpress GH. OX(2)R was found in the pars
      intermedia and in clusters of basophil cells of the anterior pituitary, which
      coexpress ACTH. These results were confirmed by double immunofluorescence
      techniques. We also found focal positivity in axon terminals of neurohypophysis,
      more intense for OX(2)R than for OX(1)R. In conclusion, these results
      demonstrated for the first time that OX(1)R and OX(2)R were expressed by
      somatotrope and corticotrope cells, respectively.

PMID- 11297594
TI  - Comparison of measured and estimated indices of insulin sensitivity and beta cell
      function: impact of ethnicity on insulin sensitivity and beta cell function in
      glucose-tolerant and normotensive subjects.
AB  - Type 2 diabetes mellitus is the result of an imbalance between insulin
      sensitivity and beta cell function. Although the assessment of these 2 parameters
      is critical for various studies, the current methods are time consuming and labor
      intensive. Recently, new estimated indices have been proposed. We examined the
      impact of ethnicity on the indices of insulin sensitivity and beta cell function
      measured from the hyperglycemic clamp and compared the results to the estimated
      indices, proposed by Matsuda and DeFronzo and Stumvoll et al., from a standard
      oral glucose tolerance test in 105 healthy, glucose-tolerant, and normotensive
      subjects from 4 ethnic groups. Among the ethnic groups, differences were noted in
      the measured insulin sensitivity (P = 0.0006) and beta cell function (P = 0.006
      for the first phase insulin response, P = 0.0002 for the second phase insulin
      response). Although the estimated indices correlated with the measured indices
      (r(2) = 0.5184--0.3014), the estimated indices barely detected the differences
      among the ethnic groups. Multivariate analysis confirmed that ethnicity had an
      independent impact for the measured indices, but had only a modest impact on the
      estimated insulin sensitivity indices and had no impact on the estimated indices
      of beta cell function. We conclude that although the estimated indices of insulin
      sensitivity and beta cell function from the oral glucose tolerance test
      correlated with the measured ones in a wide spectrum of healthy, glucose
      tolerant, and normotensive subjects, they were much less likely to detect the
      differences than measured ones among the ethnic groups.

PMID- 11297595
TI  - Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a
      multicenter, double blind, placebo-controlled trial.
AB  - We hypothesized that the administration of troglitazone, an insulin-sensitizing
      agent of the thiazolidinedione class, would improve the ovulatory dysfunction,
      hirsutism, hyperandrogenemia, and hyperinsulinemia of polycystic ovary syndrome
      (PCOS) patients. Four hundred and ten premenopausal women with PCOS in a
      multicenter, double blind trial were randomly assigned to 44 weeks of treatment
      with placebo (PBO) or troglitazone [150 mg/day (TGZ-150), 300 mg/day (TGZ-300),
      or 600 mg/day (TGZ-600)]. We compared changes in ovulatory function (by
      monitoring the urinary level of pregnanediol-3-glucuronide daily), hirsutism (by
      a modified Ferriman-Gallwey scoring method), hormonal levels (total and free
      testosterone, androstenedione, sex hormone-binding globulin, LH, FSH, and the
      LH/FSH ratio), and measures of glycemic parameters (fasting levels of glucose,
      insulin, hemoglobin A(1c), and the glucose and insulin areas under the curve
      during an oral glucose challenge) among study groups. Of the 410 patients
      recruited, 305 (74.4%) met evaluability criteria and were included in the
      analyses. The patients' baseline characteristics were similar across all
      treatment arms. Ovulatory rates were significantly greater for patients receiving
      TGZ-300 and TGZ-600 than for those receiving PBO (0.42 and 0.58 vs. 0.32; P <
      0.05 and 0.0001, respectively). Of PCOS patients treated with TGZ-600, 57%
      ovulated over 50% of the time compared with 12% of placebo-treated patients.
      There was a significant decrease in the Ferriman-Gallwey score with TGZ-600
      compared with PBO (0.22 +/- 0.53 vs. -2.21 +/- 0.49; P < 0.05, respectively).
      Free testosterone decreased and sex hormone-binding globulin increased in a dose
      related fashion with troglitazone treatment, and all three troglitazone treatment
      groups were significantly different from placebo. Nearly all glycemic parameters
      showed dose-related decreases with troglitazone treatment. The total number and
      severity of adverse events (including elevations in liver enzymes) and the
      proportion of patients withdrawn from the study due to the development of adverse
      effects were similar between treatment groups. Troglitazone improves the
      ovulatory dysfunction, hirsutism, hyperandrogenemia, and insulin resistance of
      PCOS in a dose-related fashion, with a minimum of adverse effects.

PMID- 11297596
TI  - Effects of a short-term vitamin D(3) and calcium supplementation on blood
      pressure and parathyroid hormone levels in elderly women.
AB  - Calcium supplementation is effective in reducing blood pressure in various states
      of hypertension, including pregnancy-induced hypertension and preeclampsia. In
      addition, calcitropic hormones are associated with blood pressure. The hypothesis
      is that short-term therapy with calcium and vitamin D(3) may improve blood
      pressure as well as secondary hyperparathyroidism more effectively than calcium
      monotherapy. The effects of 8 weeks of supplementation with vitamin D(3)
      (cholecalciferol) and calcium on blood pressure and biochemical measures of bone
      metabolism were studied. The sample consisted of 148 women (mean +/- SD age, 74
      +/- 1 yr) with a 25-hydroxycholecalciferol (25OHD(3)) level below 50 nmol/L. They
      received either 1200 mg calcium plus 800 IU vitamin D(3) or 1200 mg calcium/day.
      We measured intact PTH, 25OHD(3), 1,25-dihydroxyvitamin D(3), blood pressure, and
      heart rate before and after treatment. Compared with calcium, supplementation
      with vitamin D(3) and calcium resulted in an increase in serum 25OHD(3) of 72% (P
      < 0.01), a decrease in serum PTH of 17% (P = 0.04), a decrease in systolic blood
      pressure (SBP) of 9.3% (P = 0.02), and a decrease in heart rate of 5.4% (P =
      0.02). Sixty subjects (81%) in the vitamin D(3) and calcium group compared with
      35 (47%) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or
      more (P = 0.04). No statistically significant difference was observed in the
      diastolic blood pressures of the calcium-treated and calcium- plus vitamin D(3)
      treated groups (P = 0.10). Pearson coefficients of correlation between the change
      in PTH and the change in SBP were 0.49 (P < 0.01) for the vitamin D(3) plus
      calcium group and 0.23 (P < 0.01) for the calcium group. A short-term
      supplementation with vitamin D(3) and calcium is more effective in reducing SBP
      than calcium alone. Inadequate vitamin D(3) and calcium intake could play a
      contributory role in the pathogenesis and progression of hypertension and
      cardiovascular disease in elderly women.

PMID- 11297597
TI  - Weight reduction and the impaired plasma-derived free fatty acid oxidation in
      type 2 diabetic subjects.
AB  - In a previous study the oxidation of plasma free fatty acids (FFA) under baseline
      conditions and during exercise was lower in type 2 diabetic subjects compared
      with weight-matched controls. The present study intended to investigate the
      effect of weight reduction (very low calorie diet) on plasma FFA oxidation in
      seven type 2 diabetic male subjects (body fat, 37.4 +/- 1.2%; age, 51.3 +/- 3.4
      yr; plasma glucose, 7.45 +/- 0.48 mmol/L). Subjects underwent a 10-week diet
      period. Body composition and substrate utilization during rest and during bicycle
      exercise (50% of maximum aerobic capacity) were determined before and after the
      diet (during weight-stable conditions). FFA metabolism was studied by means of
      the tracer [U-(13)C]palmitate. Rates of oxidation of plasma FFA were corrected
      with an acetate recovery factor. Additionally, activities of mitochondrial
      enzymes and cytosolic fatty acid-binding protein were determined in biopsies from
      the vastus lateralis muscle before and after the diet. The very low calorie diet
      resulted in a weight loss of 15.3 kg (110.8 +/- 7.4 vs. 95.5 +/- 5.8 kg; P <
      0.01). The basal rates of appearance and disappearance of FFA decreased as a
      result of diet. The rates of appearance and disappearance of FFA during exercise
      were not different before and after diet. The oxidation of plasma-derived fatty
      acids tended to decrease after diet during baseline conditions (P = 0.10),
      whereas the plasma FFA oxidation during exercise was not different before and
      after the diet (14.1 +/- 1.9 vs. 14.8 +/- 1.8 micromol/kg fat-free mass.min).
      Skeletal muscle cytosolic fatty acid-binding protein and the activities of muscle
      oxidative enzymes did not significantly change as a result of weight loss. In
      conclusion, considerable weight reduction did not significantly improve plasma
      derived FFA oxidation under baseline conditions and during exercise, suggesting
      that this impairment reflects a primary defect leading to the development of type
      2 diabetes mellitus rather than resulting from the type 2 diabetic state.

PMID- 11297598
TI  - Predictors of the outcome of surgical treatment in acromegaly and the value of
      the mean growth hormone day curve in assessing postoperative disease activity.
AB  - Acromegaly is associated with increased morbidity and mortality unless serum GH
      levels are persistently less than 5 mU/L ( approximately 2 ng/mL) after
      treatment. Transsphenoidal surgical resection is the best available treatment for
      restoring GH to such "safe" levels; however, criteria for the assessment of the
      response to treatment are not uniform. To determine the clinically most useful
      method of assessing disease activity postoperatively and identify predictors of a
      favorable response to surgical treatment, we have analyzed 67 patients with
      acromegaly who underwent transsphenoidal surgery between 1993 and 1998. We used
      three different definitions of a satisfactory or safe response: 1) a
      postoperative mean GH less than 5 mU/L obtained from averaging five serum GH
      values obtained throughout one day; 2) a random single GH less than 5 mU/L; or 3)
      a serum insulin-like growth factor I (IGF-I) level within the normal range.
      Relying on a single GH measurement alone, 9 of the 23 patients with a single
      postoperative mean GH level less than 5 mU/L obtained at least one GH value of
      more than 5 mU/L (false positive rate, 28%) and 8 of the patients with a
      postoperative mean GH value of more than 5 mU/L obtained a single GH value of
      less than 5 mU/L (false negative rate, 15%). Postoperatively, a significant
      increase in the fluctuation of random GH values around the mean was observed in
      patients who were rendered safe (coefficient of variation, from 26 +/- 2% to 53
      +/- 6%; P < 0.001) compared with patients with persistence of inadequately
      controlled disease. However, 13% (3 of 23) of patients with mean postoperative GH
      levels of less than 5 mU/L had elevated serum IGF-I levels postoperatively, and
      17% (8 of 44) of patients with mean serum GH levels more than 5 mU/L had
      postoperative IGF-I levels within the normal range. There was no difference in
      the rate of agreement between mean GH less than 5 mU/L and normalization of IGF-I
      in relation to the interval since operation when IGF-I levels were measured.
      Preoperative tumor size and pretreatment mean GH levels were the major
      determinants of the outcome of surgery, as patients who were rendered safe had
      significantly lower preoperative mean GH levels than patients who were not cured
      (median, 31 mU/L vs. 78.5 mU/L, P < 0.01). IGF-I levels were weakly correlated
      with tumor size and could not be used to predict the patients who would be
      rendered safe. Preoperative PRL levels were higher in patients who failed to
      achieve a surgical satisfactory outcome [498 mU/L (187-857) vs. 196 mU/L (136
      315), P < 0.01]. In summary, although single random GH values and IGF-I values
      are both significantly correlated with mean GH levels, they should not be used as
      an alternative to averaging several GH values to assess disease activity, because
      of the pulsatile nature of GH secretion and the multiple factors that may
      influence serum IGF-I. Because significant discrepancies occur, particularly
      postoperatively, mean GH levels remain the more reliable indicator of surgical
      outcome and disease activity. As there is considerably more evidence relating
      long-term prognosis to serum GH levels than to IGF-I and discrepancies occur
      between GH levels and IGF-I, we suggest that mean serum GH levels and single IGF
      I levels, measured early in the postoperative period, are currently the best
      biochemical guide to the adequacy of surgery and, hence, the need for further
      treatment.

PMID- 11297599
TI  - Overexpression of glutathione-S-transferase A1 in benign adrenocortical adenomas
      from patients with Cushing's syndrome.
AB  - Benign adrenocortical adenoma is a major primary cause of Cushing's syndrome.
      Although numerous studies have been performed, the molecular mechanism of
      adrenocortical adenoma is yet to be elucidated. In this study we endeavored to
      identify genes differentially regulated in adrenocortical adenoma by suppression
      PCR-based complementary DNA (cDNA) subtractive hybridization. The cDNA population
      in atrophied nontumorous adrenal gland adjacent to the adenoma was subtracted
      from that in the adenoma. Then adenoma-specific cDNAs were amplified by PCR. We
      cloned several cDNAs that are selectively up-regulated in the adenoma, one of
      which was identified to encode glutathione-S-transferase A1 (GSTA1). Northern
      blot analysis revealed that GSTA1 messenger ribonucleic acid was abundantly
      expressed in the adenoma compared with that in the adjacent atrophied nontumorous
      gland. Western blot analysis and immunohistochemistry showed high expression of
      GSTA1 also at the protein level. In concordance with this finding, GST activity
      was significantly higher in the adenoma than in the adjacent atrophied
      nontumorous gland. To clarify the role of GSTA1 in adrenocortical cells, GST
      activity in the H295R human adrenocortical cell line was inhibited by ethacrynic
      acid. Inhibition of GSTs interfered with proliferation of the cells. We,
      therefore, hypothesize that overexpression of GSTA1 in adrenocortical adenomas
      might be involved in the growth of tumor cells. We also speculate that this
      overexpression might be an adaptive response to excess cortisol production.

PMID- 11297600
TI  - Effect of various doses of recombinant human thyrotropin on the thyroid
      radioactive iodine uptake and serum levels of thyroid hormones and thyroglobulin
      in normal subjects.
AB  - Recombinant human TSH (rhTSH), usually given as 0.9-mg doses im on 2 successive
      days, increases serum thyroglobulin (Tg) and radioactive iodine uptake (RAIU) in
      residual thyroid tissue in patients with thyroid cancer. We previously reported
      that a single, relatively low dose of rhTSH (0.1 mg im) is a potent stimulator of
      T(4), T(3), and Tg secretion in normal subjects. The present study describes the
      effects of higher doses of rhTSH on thyroid hormone and Tg secretion. Six normal
      subjects for each dose group, having no evidence of thyroid disease, received
      either 0.3 or 0.9 mg rhTSH by im injection. Serum TSH, T(4), T(3), and Tg
      concentrations were measured at 2, 4, and 8 h and 1, 2, 3, 4, and 7 days after
      rhTSH administration. The peak serum TSH concentrations were 82 +/- 18 and 277 +/
      89 mU/L, respectively, for the 0.3- and 0.9-mg doses of rhTSH. Serum T(4), T(3),
      and Tg concentrations increased significantly in subjects receiving 0.3 and 0.9
      mg rhTSH, with significant increases in T(4) and T(3) being observed before
      significant increases in serum TG: Peak concentrations of serum T(4), T(3), and
      Tg, after 0.3 mg rhTSH administration, were 100 +/- 19, 131 +/- 14, and 1035 +/-
      724% above individual baselines, respectively. Similarly, peak concentrations of
      serum T(4), T(3), and Tg, after 0.9 mg rhTSH administration, were 102 +/- 16, 134
      +/- 7, and 1890 +/- 768% above individual baselines, respectively. These data,
      compared with previously reported data for the responses to 0.1 mg rhTSH,
      indicated that 0.1, 0.3, and 0.9 mg rhTSH had similar quantitative stimulatory
      effects on thyroid hormone and Tg secretion, except that the T(4) response was
      greater in groups receiving 0.3 and 0.9 mg rhTSH than in the group receiving 0.1
      mg rhTSH. We also studied the effect of rhTSH on the thyroid RAIU in the group
      that received 0.9 mg rhTSH. The 6- and 24-h RAIU values were significantly higher
      after rhTSH (pre-rhTSH, 6-h value = 12.5 +/- 1.8%; 24 h value = 23 +/- 2.7%; post
      rhTSH, 6 h value = 27 +/- 4.8%; 24-h value = 41 +/- 4.2%). The stimulating
      effects of 0.9 mg rhTSH on the 6- and 24-h RAIUs were similar. rhTSH is a potent
      stimulator of T(4), T(3), and Tg secretion and the RAIU in normal subjects.
      Single doses greater than 0.1--0.3 mg do not seem to further enhance thyroid
      hormone or Tg secretion.

PMID- 11297601
TI  - Close association of urinary excretion of aquaporin-2 with appropriate and
      inappropriate arginine vasopressin-dependent antidiuresis in hyponatremia in
      elderly subjects.
AB  - The present study was undertaken to determine whether urinary excretion of
      aquaporin-2 (AQP-2) participates in the involvement of arginine vasopressin (AVP)
      in hyponatremia less than 130 mmol/L in 33 elderly subjects (> or =65 yr old)
      during the last 5-yr period. Subjects were separated into euvolemic hyponatremia
      groups: 13 with hypopituitarism, 8 with syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH), 8 with mineralocorticoid-responsive hyponatremia of
      the elderly, and 4 with miscellaneous diseases. Approximately 40% of those with
      hyponatremia was derived from hypopituitarism, but severe hyponatremia was found
      in the patients with SIADH and mineralocorticoid-responsive hyponatremia of the
      elderly. Plasma AVP levels remained relatively high despite hypoosmolality and
      were tightly linked with exaggerated urinary excretion of AQP-2 and antidiuresis
      in the 3 groups of patients, except for one miscellaneous one. An acute water
      load test verified the impairment in water excretion, because the percent
      excretion of the water load was less than 42% and the minimal urinary osmolality
      was not sufficiently diluted. Also, plasma AVP and urinary excretion of AQP-2
      were not reduced after the water load. The inappropriate secretion of AVP was
      evident in the patients with SIADH and hypopituitarism, and hydrocortisone
      replacement normalized urinary excretion of AQP-2 and renal water excretion in
      those with hypopituitarism. In contrast, the appropriate antidiuresis seemed to
      compensate loss of body fluid in the patients with mineralocorticoid-responsive
      hyponatremia of the elderly, who lost circulatory blood volume by 7.3% (mean).
      Fludrocortisone acetate increased renal sodium handling and body fluid, resulting
      in the reduction in AVP release and urinary excretion of AQP-2 in
      mineralocorticoid-responsive hyponatremia of the elderly. These findings indicate
      that urinary excretion of AQP-2 may be a more sensitive measure of AVP effect on
      renal collecting duct cells than are plasma AVP levels, and that increased
      urinary excretion of AQP-2 shows exaggerated AVP-induced antidiuresis in
      hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive
      hyponatremia of the elderly has to be carefully differentiated from SIADH in
      elderly subjects.

PMID- 11297602
TI  - Decreased nocturnal levels of prolactin and growth hormone in women with
      fibromyalgia.
AB  - Fibromyalgia (FM) is a complex syndrome, primarily of women, characterized by
      chronic pain, fatigue, and sleep disturbance. Altered function of the
      somatotropic axis has been documented in patients with FM, but little is known
      about nocturnal levels of PRL. As part of a laboratory study of sleep patterns in
      FM, we measured the serum concentrations of GH and PRL hourly from 2000--0700 h
      in a sample of 25 women with FM (mean, 46.9 +/- 7.6 yr) and in 21 control women
      (mean, 42.6 +/- 8.1 yr). The mean (+/-SEM ) serum concentrations (micrograms per
      L) of GH and of PRL during the early sleep period were higher in control women
      than in patients with FM [GH, 1.6 +/- 0.4 vs. 0.6 +/- 0.2 (P < 0.05); PRL, 23.2
      +/- 2.2 vs. 16.9 +/- 2.0 (P < 0.025)]. The mean serum concentrations of GH and
      PRL increased more after sleep onset in control women than in patients with FM
      [GH, 1.3 +/- 0.4 vs. 0.3 +/- 0.2 (P < 0.05); PRL, 16.2 +/- 2.4 vs. 9.7 +/- 1.5 (P
      < 0.025)]. Sleep efficiency and amounts of sleep or wake stages on the blood draw
      night were not different between groups. There was a modest inverse relationship
      between sleep latency and PRL and a direct relationship between sleep efficiency
      and PRL in FM. There was an inverse relationship between age and GH most evident
      in control women. Insulin-like growth factor I levels were not different between
      the groups. These data demonstrate altered functioning of both the somatotropic
      and lactotropic axes during sleep in FM and support the hypothesis that
      dysregulated neuroendocrine systems during sleep may play a role in the
      pathophysiology of FM.

PMID- 11297603
TI  - Effect of low-density lipoprotein apheresis on kinetics of apolipoprotein B in
      heterozygous familial hypercholesterolemia.
AB  - The acute reduction of low-density lipoprotein (LDL) cholesterol obtained by LDL
      apheresis allows the role of the high level of circulating LDL on lipoprotein
      metabolism in heterozygous familial hypercholesterolemia (heterozygous FH) to be
      addressed. We studied apolipoprotein B (apoB) kinetics in five heterozygous FH
      patients before and the day after an apheresis treatment using endogenous
      labeling with [(2)H(3)]leucine. Compared with younger control subjects,
      heterozygous FH patients before apheresis showed a significant decrease in the
      fractional catabolic rate of LDL (0.24 +/- 0.08 vs. 0.65 +/- 0.22 day(-1); P <
      0.01), and LDL production was increased in heterozygous FH patients (18.9 +/- 7.0
      vs. 9.9 +/- 4.2 mg/kg.day; P < 0.05). The modeling of postapheresis apoB kinetics
      was performed using a nonsteady state condition, taking into account the changing
      pool size of very low density lipoprotein (VLDL), intermediate density
      lipoprotein, and LDL apoB. The postapheresis kinetic parameters did not show
      statistical differences compared with preapheresis parameters in heterozygous FH
      patients; however, a trend for increases in fractional catabolic rate of LDL
      (0.24 +/- 0.08 vs. 0.35 +/- 0.09 day(-1); P = 0.067) and the production of VLDL
      (13.7 +/- 8.3 vs. 21.9 +/- 1.6 mg/kg.day; P = 0.076) was observed. These results
      suggested that the marked decrease in plasma LDL obtained a short time after LDL
      apheresis is able to stimulate LDL receptor activity and VLDL production in
      heterozygous FH.

PMID- 11297604
TI  - CTLA-4 and not CD28 is a susceptibility gene for thyroid autoantibody production.
AB  - One of the hallmarks of the human autoimmune thyroid diseases (AITDs) is the
      production of high titers of autoantibodies against thyroglobulin and thyroid
      peroxidase that often precedes the development of clinical disease. A high
      percentage of family members of patients with AITDs have significant titers of
      thyroid antibodies (TAbs), suggesting a genetic predisposition for their
      development, and segregation analyses have favored a dominant mode of
      inheritance. The aim of the present study was to identify the susceptibility
      genes for TAb production. We completed a genome-wide scan in 56 multiplex
      families (323 individuals) in which all family members with AITDs and/or
      detectable TAbs were considered affected. The highest 2-point logarithm of odds
      (LOD) score of 3.6 was obtained for marker D2S325 on chromosome 2q33 at 210.9
      centimorgans. This locus showed no evidence for linkage to Graves' disease or
      Hashimoto's thyroiditis (2-point LOD scores, 0.42 for Graves' disease and -0.60
      for Hashimoto's thyroiditis), demonstrating that the gene in this region
      conferred susceptibility to TAbs, but that clinical disease development required
      additional genetic and/or environmental factors. We then fine-mapped the region
      linked with TAbs using 11 densely spaced microsatellite markers. Multipoint
      linkage analysis using these markers showed a maximum LOD score of 4.2 obtained
      for marker D2S155 at 209.8 centimorgans (with heterogeneity, alpha = 0.41). As
      the linked region contained the CTLA-4 and CD28 genes, we then tested whether
      they were the susceptibility genes for TAbs on chromosome 2q33. The CD28 gene was
      sequenced in 15 individuals, and a new C/T single nucleotide polymorphism (SNP)
      was identified in intron 3. Analysis of this SNP revealed no association with
      TAbs in the probands of the linked families (families that were linked with
      D2S155) compared with controls. The CTLA-4 gene was analyzed using the known
      A/G(49) SNP, and the results showed a significantly increased frequency of the G
      allele in the probands of the linked families compared with the probands of the
      unlinked families or with controls (P = 0.02). We concluded that 1) a major gene
      for thyroid autoantibody production was located on chromosome 2q33; 2) the TAb
      gene on chromosome 2q33 was most likely the CTLA-4 gene and not the CD28 gene;
      and 3) CTLA-4 contributed to the genetic susceptibility to TAb production, but
      there was no evidence that it contributed specifically to Graves' or Hashimoto's
      diseases.

PMID- 11297605
TI  - Investigating the paradox of hypothyroidism and increased serum thyrotropin (TSH)
      levels in Sheehan's syndrome: characterization of TSH carbohydrate content and
      bioactivity.
AB  - Serum TSH levels are often paradoxically elevated in patients with hypothyroidism
      due to Sheehan's syndrome. To investigate this apparent discrepancy, the
      biological activity and glycosylation of serum TSH were studied in 9 untreated
      patients with Sheehan's syndrome and 11 normal controls. TSH bioassay was based
      on cAMP generation, measured by RIA, in a culture system of CHO cells transfected
      with recombinant human TSH receptor. The oligosaccharide branching of TSH was
      studied by Con A lectin affinity chromatography, which discriminates TSH isoforms
      according to their mannose content, and the sialic acid content of TSH was
      studied by Ricinus communis affinity chromatography in combination with enzymatic
      removal of sialic acid with neuraminidase treatment. TSH bioactivity was
      expressed as the ratio between biological and immunofluorometric assays (B/I).
      Bioactive TSH concentrations were calculated by multiplying serum TSH intrinsic
      bioactivity by serum immunoreactive TSH concentration (B/I x I). Serum free T(4)
      (FT(4)) levels were lower in patients than in controls (3.7 +/- 0.4 vs. 14.0 +/-
      0.9 pmol/L, respectively; P < 0.0001). Circulating immunoreactive TSH was higher
      in patients with Sheehan's syndrome than in controls (3.8 +/- 0.8 vs. 1.8 +/- 0.2
      mU/L, respectively; P = 0.01). In contrast, TSH B/I was significantly decreased
      in Sheehan's patients compared with controls (0.6 +/- 0.4 vs. 1.7 +/- 0.8,
      respectively; P = 0.003). However, the resultant bioactive TSH concentrations in
      serum of Sheehan's patients were not significantly different from control values
      (2.1 +/- 0.6 vs. 3.0 +/- 0.4; P = 0.25). A significant correlation was found
      between the bioactive TSH concentrations and serum FT(4) levels in patients with
      Sheehan's syndrome (r = 0.66; P = 0.05), but not between serum immunoreactive TSH
      and FT(4) levels (r = 0.21; P = 0.59) or between intrinsic TSH bioactivity and
      FT(4) levels (r = 0.56; P = 0.12). The Con A chromatography of serum TSH showed a
      similar distribution (0.3 < P < 0.5) of unbound, weakly bound, and firmly bound
      TSH in Sheehan's patients (16%, 38%, and 47%, respectively) and controls (15%,
      34%, and 52%, respectively). The ricin chromatography of serum TSH showed a
      higher proportion of sialylated TSH molecules in Sheehan's patients than in
      controls (55% vs. 29%; P = 0.02). These results show that circulating TSH in
      Sheehan's syndrome, albeit increased, has decreased biological activity. The
      relevance of this finding is supported by the direct correlation between
      bioactive serum TSH concentrations and circulating FT(4). The reduced intrinsic
      TSH bioactivity in pituitary hypothyroidism of Sheehan's syndrome results from
      increased sialylation of TSH.

PMID- 11297606
TI  - Regional variations of insulin-like growth factor I (IGF-I), IGF-II, and receptor
      type I in benign prostatic hyperplasia tissue and their correlation with
      intraprostatic androgens.
AB  - Benign prostatic hyperplasia (BPH) is an androgen-dependent disease; it
      originates exclusively in the inner prostate, which includes tissue surrounding
      the urethra. Stromal-epithelial interaction has a pivotal role in the regulation
      of the development and growth of the prostate, and locally produced peptide
      growth factors are considered important mediators of this interaction. Insulin
      like growth factor I (IGF-I) and IGF-II, acting mainly through type 1 IGF
      receptor (IGFR1), have mitogenic and antiapoptotic effects on epithelial and
      stromal prostatic cells. In this study the expression of IGF-I, IGF-II, and IGFR1
      messenger ribonucleic acid (mRNA), the immunoreactive content of IGF-I (irIGF-I)
      and IGF-II (irIGF-II) were determined in periurethral, intermediate, and
      subcapsular regions of BPH tissue to verify their possible regional variation; a
      correlation to the tissue levels of dihydrotestosterone (DHT) and 3 alpha
      androstanediol (3 alpha Diol) was also determined to verify their possible
      androgen dependence. Prostates were removed by suprapubic prostatectomy from 14
      BPH patients and sectioned in the periurethral, intermediate, and subcapsular
      regions. Gene expression of IGF-I, IGF-II, and IGFR1 was evaluated by
      semiquantitative RT-PCR, using beta-actin as a control. irIGF-I was measured by
      RIA, and irIGF-II was measured by IRMA after acidification and chromatography on
      Sep-Pak C(18) cartridges. DHT and 3 alpha Diol concentrations were evaluated by
      RIA after extraction and purification on Celite microcolumns. IGF-II and IGFR1,
      but not IGF-I, mRNA was higher in the periurethral than in the intermediate (P <
      0.05) and subcapsular (P < 0.01) region. Also, prostatic levels of irIGF-II,
      expressed as picomoles per g tissue, were higher in the periurethral (20.84 +/-
      1.84) than in the intermediate (14.81 +/- 2.11; P < 0.05) and subcapsular (10.88
      +/- 1.21; P < 0.001) region. No significant differences were found in irIGF-I
      content. Considering prostatic androgen levels, DHT and 3alphaDiol presented a
      regional variation, with the highest concentrations in the periurethral region.
      IGF-II mRNA and irIGF-II levels were positively correlated with both DHT and 3
      alpha Diol content. These results demonstrate that in BPH tissue a greater IGF-II
      activity is present in the periurethral region, the site of origin of BPH.
      Moreover, we can hypothesize that the tissue androgen content may modulate
      prostatic production of IGF-II, acting at the transcriptional and probably the
      posttranscriptional level. Therefore, even though further studies will need to
      confirm this hypothesis, DHT may increase IGF-II activity, mainly in the
      periurethral region, which, in turn, induces, through IGFR1, benign proliferation
      of both epithelial and stromal cells, characteristic of BPH.

PMID- 11297607
TI  - Aberrant expression of Cyr61, a member of the CCN (CTGF/Cyr61/Cef10/NOVH) family,
      and dysregulation by 17 beta-estradiol and basic fibroblast growth factor in
      human uterine leiomyomas.
AB  - Uterine leiomyomas are the most common tumors of the reproductive tract,
      afflicting women between the ages of 30--55 yr. Although considered to be the
      leading cause of hysterectomies in the United States, little is known of the
      etiology and mechanisms of pathogenesis in leiomyomas. Accordingly, rapid
      analysis of differential expression (RADE) was employed to identify genes that
      are abnormally expressed in leiomyomas. Of the several genes identified, Cyr61, a
      member of the CCN family of growth and angiogenic regulators, was shown to be
      markedly down-regulated at the messenger ribonucleic acid (mRNA) and protein
      levels in leiomyoma tumors compared with the matched uterine myometrial controls
      (n = 38). In addition, in situ hybridization experiments corroborated the lack of
      Cyr61 expression in leiomyoma cells, whereas abundant transcript levels were
      identified in adjacent myometrial smooth muscle cells. To elucidate the
      mechanisms of Cyr61 gene regulation in leiomyomas, we determined the effects of
      ovarian steroids, basic fibroblast growth factor (bFGF), and serum, on Cyr61
      expression using an ex vivo culture system. Treatment of human myometrial
      explants with 17 beta-estradiol and bFGF up-regulated Cyr61 transcripts, whereas
      the progesterone receptor agonist, R5020 (alone or in combination with 17 beta
      estradiol), had no effect. Paradoxically, neither 17 beta-estradiol nor bFGF was
      capable of up-regulating Cyr61 mRNA in leiomyoma explants despite elevated levels
      of ER alpha mRNA, suggesting a possible defect in steroid and growth factor
      regulation. Thus, dysregulation of Cyr61 by estrogen and bFGF may contribute to
      down-regulation of Cyr61 in leiomyomas, which, in turn, may predispose uterine
      smooth muscle cells toward sustained growth.

PMID- 11297608
TI  - Binding and functional studies with the growth hormone receptor antagonist, B2036
      PEG (pegvisomant), reveal effects of pegylation and evidence that it binds to a
      receptor dimer.
AB  - GH actions are dependent on receptor dimerization. The GH receptor antagonist,
      B2036-PEG, has been developed for treating acromegaly. B2036 has mutations in
      site 1 to enhance receptor binding and in site 2 to block receptor dimerization.
      Pegylation (B2036-PEG) increases half-life and lowers immunogenicity, but high
      concentrations are required to control insulin-like growth factor-I levels. We
      examined antagonist structure and function and the impact of pegylation on
      biological efficacy. Unpegylated B2036 had a 4.5-fold greater affinity for GH
      binding protein (GHBP) than GH but similar affinity for membrane receptor.
      Pegylation substantially reduced membrane binding affinity and receptor
      antagonism, as assessed by a transcription assay, by 39- and 20-fold,
      respectively. GHBP reduced antagonist activity of unpegylated B2036 but did not
      effect antagonism by B2036-PEG. B2036 down-regulated receptors, and membrane
      binding sites doubled in the presence of dimerization-blocking antibodies,
      suggesting that B2036 binds to a receptor dimer. It is concluded that the high
      concentration requirement of B2036-PEG for clinical efficacy relates to
      pegylation, which decreases binding to membrane receptor but has the advantages
      of reduced clearance, immunogenicity, and interactions with GHBP. Our studies
      suggest that B2036 binds to a receptor dimer and induces internalization but not
      signaling.

PMID- 11297609
TI  - Paracrine stimulation of capillary endothelial cell migration by endometrial
      tissue involves epidermal growth factor and is mediated via up-regulation of the
      urokinase plasminogen activator receptor.
AB  - Endometrial angiogenesis is not well studied, but has potential as a model for
      studies of physiological angiogenesis. Migration as well as proliferation of
      vascular endothelial cells are modulated by other endometrial cells. This study
      analyzes the chemotactic signal released from endometrial tissue in a wound assay
      using human microvascular endothelial cells. Endometrial tissue explants
      stimulate migration, and this effect is significantly weaker with explants taken
      at midcycle than those obtained earlier or later in the cycle. Migration is
      inhibited more than 50% by either blocking antibodies to the urokinase
      plasminogen activator receptor (uPAR) or enzymatic removal of uPAR from the cell
      surface. Also, migration is inhibited more than 50% by antibodies to epidermal
      growth factor (EGF), but not by antibodies to vascular endothelial growth factor
      or basic fibroblast growth factor. The combination of anti-EGF and anti-uPAR
      antibodies does not further reduce the response, suggesting that these antibodies
      target a common pathway. Conditioned medium from endometrial explants contains
      EGF, and EGF stimulates the migration of endothelial cells in a dose-dependent
      way. This effect is completely blocked by antibodies to uPAR. These data suggest
      up-regulation of the uPA system by EGF. Conditioned medium from EGF-treated cells
      contains less uPA than medium from control cells. In contrast, binding of
      radiolabeled uPA reveals an increased number of uPA-binding sites in EGF-treated
      cells. Increased expression of uPAR potentially increases the activation and
      assembly of focal adhesion sites, a prerequisite for cell migration. We conclude
      that the endometrial migratory signal has two components. The major part of the
      signal is blocked by antibodies to EGF, and the response is mediated via up
      regulation of uPAR in the endothelial cells. The other part of the signal is
      unknown, and the response does not involve uPAR. Decreased endometrial
      chemotactic signal at midcycle is probably related to decreased release of EGF,
      which is secondary to increased binding to endometrial cell membranes.

PMID- 11297610
TI  - Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after
      administration of 22-kDa recombinant human GH in trained adult males.
AB  - GH is being used by elite athletes to enhance sporting performance. To examine
      the hypothesis that exogenous 22-kDa recombinant human GH (rhGH) administration
      could be detected through suppression of non-22-kDa isoforms of GH, we studied
      seventeen aerobically trained males (age, 26.9 +/- 1.5 yr) randomized to rhGH or
      placebo treatment (0.15 IU/kg/day for 1 week). Subjects were studied at rest and
      in response to exercise (cycle-ergometry at 65% of maximal work capacity for 20
      min). Serum was assayed for total GH (Pharmacia IRMA and pituitary GH), 22-kDa GH
      (2 different 2-site monoclonal immunoassays), non-22-kDa GH (22-kDa GH-exclusion
      assay), 20-kDa GH, and immunofunctional GH. In the study, 3 h after the last dose
      of rhGH, total and 22-kDa GH concentrations were elevated, reflecting exogenous
      22-kDa GH. Non-22-kDa and 20-kDa GH levels were suppressed. Regression of non-22
      kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of
      treatment groups. In identical exercise studies repeated between 24 and 96 h
      after cessation of treatment, the magnitude of the responses of all GH isoforms
      was suppressed (P < 0.01), but the relative proportions were similar to those
      before treatment. We conclude: 1) supraphysiological doses of rhGH in trained
      adult males suppressed exercise-stimulated endogenous circulating isoforms of GH
      for up to 4 days; 2) the clearest separation of treatment groups required the
      simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22
      kDa GH concentrations; and 3) these methods may prove useful in detecting rhGH
      abuse in athletes.

PMID- 11297611
TI  - Identification, characterization, and biological activity of specific receptors
      for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in
      human breast carcinomas and cell lines.
AB  - The family of GH secretagogues (GHS) includes synthetic peptidyl (hexarelin) and
      nonpeptidyl (MK-0677) molecules possessing specific receptors in the pituitary
      and central nervous system as well as in peripheral tissues, including the heart
      and some endocrine organs. A gastric-derived peptide, named ghrelin, has recently
      been proposed as the natural ligand of the GHS receptors (GHS-Rs). The presence
      of specific GHS-Rs has now been investigated in nontumoral and neoplastic human
      breast tissue using a radioiodinated peptidyl GHS ([(125)I]-Tyr-Ala-hexarelin) as
      ligand. Specific binding sites for GHS were detected in membranes from several
      types of breast carcinomas, whereas a negligible binding was found in
      fibroadenomas and mammary parenchyma. The highest binding activity was found in
      well-differentiated (G1) invasive breast carcinomas and was progressively reduced
      in moderately (G2) to poorly (G3) differentiated tumors. [(125)I]-Tyr-Ala
      hexarelin bound to tumor membranes was displaced by different unlabeled GHS such
      as hexarelin, Tyr-Ala-hexarelin, human ghrelin, and MK-0677 as well as by
      desoctanoyl-ghrelin and hexarelin derivative EP-80317, which are devoid of GH
      releasing properties in vivo. In contrast, no competition was seen between
      radiolabeled Tyr-Ala-hexarelin and some peptides (CRF and insulin-like growth
      factor I) structurally and functionally unrelated to hexarelin or when GHRH and
      SRIF were tested in the displacement studies. The presence of specific GHS
      binding sites was also demonstrated in three different human breast carcinoma
      cell lines (MCF7, T47D, and MDA-MB231), in which, surprisingly, no messenger RNA
      for GHS-R1a was demonstrated by RT-PCR. In these cell lines, ghrelin (as well as
      hexarelin, MK-0677, EP-80317, and even desoctanoyl ghrelin) caused a significant
      inhibition of cell proliferation at concentrations close to their binding
      affinity. In conclusion, this study provides the first demonstration of specific
      GHS binding sites, other than GHS-R1, in breast cancer. These receptors probably
      mediate growth inhibitory effects on breast carcinoma cells in vitro.

PMID- 11297612
TI  - Screening for mutations in the steroidogenic acute regulatory protein and
      steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal
      adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic
      hirsute women.
AB  - Abstract Abnormalities in adrenal and/or ovarian steroidogenesis are found in
      most patients with hirsutism. The rate-limiting step in the synthesis of steroids
      in the ovary and the adrenal is the conversion of cholesterol into pregnenolone
      by cholesterol side-chain cleavage enzyme (P450scc), encoded by the gene CYP11A,
      after cholesterol is introduced into the mitochondria by the steroidogenic acute
      regulatory protein (StAR). DAX-1 is a repressor of StAR gene expression, and
      steroidogenic factor-1 (SF-1) is a regulator of CYP11A, DAX-1, and StAR gene.
      Mutations in any of these factors resulting in gain of function, or loss of
      repression, of StAR or P450scc might contribute to the steroidogenic
      abnormalities present in hirsute patients. In the present study we have screened,
      using heteroduplex analysis, the genes encoding StAR and SF-1 as well as DAX-1
      and CYP11A for mutations in genomic DNA from 19 women presenting with hirsutism
      and increased serum androgen levels. When variants were found, analysis was
      extended to a larger group of hyperandrogenic patients and nonaffected women. Two
      variants were identified in the SF-1 gene. A G-->C change in exon 6, resulting in
      an Arg(365)Pro mutation, was found in 1 of 45 patients, but not in controls.
      Also, a Gly(146)Ala missense mutation, resulting from a G-->C change in exon 4,
      was found in 2 of 48 patients and in 2 of 50 nonaffected individuals. We
      identified a C-->T base pair change at position -33 of the StAR gene. Three of 48
      patients and 3 of 43 controls presented this variant. No mutations were found in
      coding regions of the StAR gene. Analysis of CYP11A-coding regions identified a G
      ->A change in exon 3, resulting in a Val(179)Ile missense mutation. This mutation
      was found in 1 of 29 patients studied and was not present in 50 controls.
      Finally, analysis of DAX-1 showed no variant in any of the women studied. In
      conclusion, mutations in StAR, SF-1, CYP11A, and DAX-1 are seldom found in
      hirsute patients and do not explain the steroidogenic abnormalities found in
      these women.

PMID- 11297613
TI  - Phytochemical glyceollins, isolated from soy, mediate antihormonal effects
      through estrogen receptor alpha and beta.
AB  - The flavonoid family of phytochemicals, particularly those derived from soy, has
      received attention regarding their estrogenic activity as well as their effects
      on human health and disease. In addition to these flavonoids other
      phytochemicals, including phytostilbene, enterolactone, and lignans, possess
      endocrine activity. The types and amounts of these compounds in soy and other
      plants are controlled by both constitutive expression and stress-induced
      biosynthesis. The health benefits of soy-based foods may, therefore, be dependent
      upon the amounts of the various hormonally active phytochemicals within these
      foods. The aim was to identify unique soy phytochemicals that had not been
      previously assessed for estrogenic or antiestrogenic activity. Here we describe
      increased biosynthesis of the isoflavonoid phytoalexin compounds, glyceollins, in
      soy plants grown under stressed conditions. In contrast to the observed
      estrogenic effects of coumestrol, daidzein, and genistein, we observed a marked
      antiestrogenic effect of glyceollins on ER signaling, which correlated with a
      comparable suppression of 17 beta-estradiol-induced proliferation in MCF-7 cells.
      Further evaluation revealed greater antagonism toward ER alpha than ER beta in
      transiently transfected HEK 293 cells. Competition binding assays revealed a
      greater affinity of glyceollins for ER alpha vs. ER beta, which correlated to
      greater suppression of ER alpha signaling with higher concentrations of
      glyceollins. In conclusion, we describe the phytoalexin compounds known as
      glyceollins, which exhibit unique antagonistic effects on ER in both HEK 293 and
      MCF-7 cells. The glyceollins as well as other phytoalexin compounds may represent
      an important component of the health effects of soy-based foods.

PMID- 11297614
TI  - Glucagon-like peptide 2.
AB  - Glucagon-like peptide 2 (GLP-2) is a 33 amino acid peptide-encoded
      carboxyterminal to the sequence of GLP-1 in the proglucagon gene. Both GLP-1 and
      GLP-2 are secreted from gut endocrine cells and promote nutrient absorption
      through distinct mechanisms of action. GLP-2 regulates gastric motility, gastric
      acid secretion, intestinal hexose transport, and increases the barrier function
      of the gut epithelium. GLP-2 significantly enhances the surface area of the
      mucosal epithelium via stimulation of crypt cell proliferation and inhibition of
      apoptosis in the enterocyte and crypt compartments. The cytoprotective and
      reparative effects of GLP-2 are evident in rodent models of experimental
      intestinal injury. GLP-2 reduces mortality and decreases mucosal injury, cytokine
      expression, and bacterial septicemia in the setting of small and large bowel
      inflammation. GLP-2 also enhances nutrient absorption and gut adaptation in
      rodents or humans with short bowel syndrome. The actions of GLP-2 are transduced
      by the GLP-2 receptor, a G protein-coupled receptor expressed in gut endocrine
      cells of the stomach, small bowel, and colon. Activation of GLP-2 receptor
      signaling in heterologous cells promotes resistance to apoptotic injury in vitro.
      The cytoprotective, reparative, and energy-retentive properties of GLP-2 suggests
      that GLP-2 may potentially be useful for the treatment of human disorders
      characterized by injury and/or dysfunction of the intestinal mucosal epithelium.

PMID- 11297615
TI  - Regulated expression of prostaglandin E(2) receptors EP2 and EP4 in human ovarian
      granulosa-luteal cells.
AB  - Prostaglandins (PGs) have been implicated in regulation of ovarian function. We
      have previously shown that the expression of cyclooxygenase-2 and the receptor
      for PGF(2 alpha) are expressed in periovulatory human granulosa cells and
      upregulated by gonadotropins and cytokines in cultured human ovarian granulosa
      luteal (GL) cells. We now show that transcripts for PGE(2) receptor subtypes EP2
      and EP4 are expressed in freshly isolated human granulosa cells and in mouse
      ovaries as detected by Northern blot analysis. However, EP2 and EP4 receptor mRNA
      levels were low or nondetectable in cultured human GL cells suggesting that these
      transcripts may be under hormonal and/or cytokine regulation in the ovaries in
      vivo. Indeed, the proinflammatory cytokine interleukin-1 beta (IL-1 beta)
      stimulated expression of EP2 and EP4 transcripts in concentration- and time
      dependent manner in the GL cells. Furthermore, the transcript for EP2 receptor
      was localized in the corpus luteum of the mouse ovary by in situ hybridization,
      and EP2 protein was expressed in human corpus luteum as detected by
      immunohistochemistry. Our data suggest that IL-1 beta induces expression of EP2
      and EP4 receptors in human GL cells, and that EP2 receptor is expressed in both
      human and murine luteal glands.

PMID- 11297616
TI  - Angiogenesis inhibition in the in vivo antineoplastic effect of manumycin and
      paclitaxel against anaplastic thyroid carcinoma.
AB  - Our laboratory has investigated the anticancer effects of combined manumycin (a
      farnesyltransferase inhibitor) and paclitaxel (a microtubule inhibitor) against
      anaplastic thyroid carcinoma (ATC). In this study we reported the in vivo
      efficacy of this combination against ATC cells and the lack of toxicity of this
      treatment in mice. We observed that manumycin-treated tumors looked paler than
      both control and paclitaxel-treated tumors. We hypothesized that angiogenesis
      inhibition mediated part of the in vivo effect of manumycin. This hypothesis was
      supported by the findings that manumycin significantly inhibited angiogenesis (as
      directly demonstrated by measurement of hemoglobin content and vascular area) in
      Matrigel implanted into mice, that manumycin decreased the vascular endothelial
      growth factor in hypoxic ATC cells, and that both manumycin and paclitaxel
      inhibited endothelial cell proliferation. Interestingly, inhibition of
      endothelial tubule formation in Matrigel was enhanced by combining manumycin and
      paclitaxel. As angiogenesis and tumor growth are continuous processes, we
      investigated the effect of sustained delivery of manumycin and found that
      paclitaxel plus slow release manumycin (13.25 mg/kg x week) inhibited ATC
      xenografts more than paclitaxel plus intermittent manumycin (15 mg/kg x week). In
      conclusion, manumycin plus paclitaxel is an effective combination against ATC,
      and inhibition of angiogenesis plays a role in the antineoplastic effect of this
      combination.

PMID- 11297617
TI  - Macroorchidism due to autonomous hyperfunction of Sertoli cells and G(s)alpha
      gene mutation: an unusual expression of McCune-Albright syndrome in a prepubertal
      boy.
AB  - We report an unusual observation of a 3.8-yr-old boy with McCune-Albright
      syndrome (MAS) associated with abnormal prepubertal testis enlargement and no
      sexual precocity. Physical examination showed cafe-au-lait skin lesions, enlarged
      testes, prepubertal sized penis, and no pubic or axillary hair. Skeletal
      radiography disclosed fibrous dysplasia. The serum testosterone level was 0.58
      nmol/L and remained below 1.4 nmol/L during the 4-yr follow-up. By contrast,
      serum inhibin B and anti-Mullerian hormone concentrations were abnormally
      increased up to 255 pg/mL (childhood range, 35--180) and 792 pmol/L (childhood
      range, 309--566), respectively. The LH response to a GnRH test was in the
      prepubertal range, whereas the FSH response was blunted. This abnormal hormone
      concentration profile indicates autonomous hyperfunction of Sertoli cells, with
      no evidence of Leydig cell activation. Testicular histology showed tubules with
      marked Sertoli cell hyperplasia and very rare germinal cells, and interstitial
      tissue containing mesenchymal cells but no mature Leydig cells. DNA sequence
      analysis from bone and testis tissues detected the known activating mutation in
      MAS that results in replacement of Arg by His at codon 201 of the G(s)alpha
      protein. Other endocrine tests showed excessive GH secretion and moderate adrenal
      androgen hypersecretion. These findings are consistent with the occurrence of an
      activating mutation of the G(s)alpha gene mainly expressed in Sertoli cells and
      weakly expressed or absent in Leydig cells. Abnormal prepubertal testicular
      enlargement extends the clinical spectrum of MAS, suggesting that determination
      of serum inhibin B and anti-Mullerian hormone should be considered in boys with
      this syndrome. This observation demonstrates the usefulness of detailed molecular
      and biological investigations in atypical cases of MAS.

PMID- 11297618
TI  - Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in
      the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase.
AB  - The hyperinsulinism/hyperammonemia (HI/HA) syndrome is a form of congenital
      hyperinsulinism in which affected children have recurrent symptomatic
      hypoglycemia together with asymptomatic, persistent elevations of plasma ammonium
      levels. We have shown that the disorder is caused by dominant mutations of the
      mitochondrial enzyme, glutamate dehydrogenase (GDH), that impair sensitivity to
      the allosteric inhibitor, GTP. In 65 HI/HA probands screened for GDH mutations,
      we identified 19 (29%) who had mutations in a new domain, encoded by exons 6 and
      7. Six new mutations were found: Ser(217)Cys, Arg(221)Cys, Arg(265)Thr,
      Tyr(266)Cys, Arg(269)Cys, and Arg(269)HIS: In all five mutations tested,
      lymphoblast GDH showed reduced sensitivity to allosteric inhibition by GTP
      (IC(50), 60--250 vs. 20--50 nmol/L in normal subjects), consistent with a gain of
      enzyme function. Studies of ATP allosteric effects on GDH showed a triphasic
      response with a decrease in high affinity inhibition of enzyme activity in HI/HA
      lymphoblasts. All of the residues altered by exons 6 and 7 HI/HA mutations lie in
      the GTP-binding domain of the enzyme. These data confirm the importance of
      allosteric regulation of GDH as a control site for amino acid-stimulated insulin
      secretion and indicate that the GTP-binding site is essential for regulation of
      GDH activity by both GTP and ATP.

PMID- 11297619
TI  - Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein
      receptors in humans is associated with abnormal breast development and tooth
      impaction.
AB  - Recent studies in transgenic mice have demonstrated that PTH-related protein
      (PTHrP), signaling through the type 1 PTH/PTHrP receptor (PTHR1), regulates
      endochondral bone development and epithelial-mesenchymal interactions during the
      formation of the mammary glands and teeth. Recently, it has been shown that loss
      of-function mutations in the PTHR1 gene result in a rare, lethal form of dwarfism
      known as Blomstrand chondrodysplasia. These patients suffer from severe defects
      in endochondral bone formation, but abnormalities in breast and tooth development
      have not been reported. To ascertain whether PTHrP signaling was important to
      human breast and tooth development, we studied two fetuses with Blomstrand
      chondrodysplasia. These fetuses lack nipples and breasts. Developing teeth were
      present, but they were severely impacted within the surrounding alveolar bone,
      leading to distortions in their architecture and orientation. Compatible with the
      involvement of PTHR1 and PTHrP in human breast and tooth morphogenesis, both were
      expressed within the developing breasts and teeth of normal human fetuses.
      Therefore, impairment of the PTHrP/PTHR1 signaling pathway in humans is
      associated with severe abnormalities in tooth and breast development. In addition
      to regulating human bone formation, this signaling pathway is also necessary for
      the normal development of the human breast and tooth.

PMID- 11297620
TI  - Insulin production in a neuroectodermal tumor that expresses islet factor-1, but
      not pancreatic-duodenal homeobox 1.
AB  - We studied a 60-yr-old female with a brain tumor who showed severe symptoms of
      hypoglycemia (plasma glucose, 2.2 mmol/L) and hyperinsulinemia (1.28 nmol/L)
      after radiotherapy. The cystic brain tumor contained proinsulin and insulin at
      concentrations of 13.6 and 1.22 nmol/L, respectively. Immunohistochemical studies
      showed the tumor cells were ectodermal in origin but not endodermal, based on
      three diagnostic features of neuroectodermal tumors 1) pseudorosette formation
      noted under light microscopy, 2) finding of a small number of dense core
      neurosecretory granules on electron microscopy, and 3) positive immunostaining
      for both neuronal specific enolase and protein gene product 9.5. These cells also
      expressed the transcription factor, neurogenin-3, NeuroD/beta 2, and islet factor
      I, which are believed to be transcription factors in neuroectoderm as well as in
      pancreatic islet cells, but not pancreatic-duodenal homeobox 1, Pax4, or Nkx2.2.
      In addition, they did not express glucagon, somatostatin, or glucagon-like
      peptide-1. Our results show the presence of proinsulin in an ectoderm cell brain
      tumor that does not express the homeobox gene, pancreatic-duodenal homeobox 1,
      but expresses other transcription factors, i.e. neurogenin3, NeuroD/beta 2, and
      islet factor-1, which are related to insulin gene expression in the brain tumor.

PMID- 11297621
TI  - Somatic mutation and germline variants of MINPP1, a phosphatase gene located in
      proximity to PTEN on 10q23.3, in follicular thyroid carcinomas.
AB  - Various genes have been identified to play a role in the pathogenesis of
      follicular thyroid tumors. Cowden syndrome is the only known familial syndrome
      with an increased risk of both follicular thyroid adenoma (FA) and carcinoma
      (FTC). Germline mutations in the tumor suppressor gene PTEN, which encodes a dual
      specificity phosphatase, have been found in up to 80% of patients with Cowden
      syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid
      tumors. Although somatic intragenic mutations in PTEN, which maps to 10q23.3, are
      rarely found in follicular tumors, loss of heterozygosity (LOH) of markers within
      10q22-24 occurs in about 25%. Recently, another phosphatase gene, MINPP1, has
      been localized to 10q23.3. MINPP1 has the ability to remove 3-phosphate from
      inositol phosphate substrates, a function that overlaps that of PTEN. Because of
      this overlapping function with PTEN and the physical location of MINPP1 to a
      region with frequent LOH in follicular thyroid tumors, we considered it to be an
      excellent candidate gene that could contribute to the pathogenesis of follicular
      thyroid tumors. We analyzed DNA from tumor and corresponding normal tissue from
      23 patients with FA and 15 patients with FTC for LOH and mutations at the MINPP1
      locus. LOH was identified in four malignant and three benign tumors. One of these
      FTCs with LOH was found to harbor a somatic c.122C > T or S41L mutation. We also
      found two germline sequence variants, c.809A > G (Q270R) and IVS3 + 34T > A. The
      c.809A > G variant was found in only one patient with FA but not in patients with
      FTC or normal controls. More interestingly, IVS3 + 34T > A was found in about 15%
      of FA cases and normal controls but not in patients with FTC. These results
      suggest a role for MINPP1 in the pathogenesis of at least a subset of malignant
      follicular thyroid tumors, and MINPP1 might act as a low penetrance
      predisposition allele for FTC.

PMID- 11297622
TI  - Transferrin is an insulin-like growth factor-binding protein-3 binding protein.
AB  - Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) possesses both
      growth-inhibitory and -potentiating effects on cells that are independent of IGF
      action and are mediated through specific IGFBP-3 binding proteins/receptors
      located at the cell membrane, cytosol, or nuclear compartments and in the
      extracellular matrix. We have here characterized transferrin (Tf) as one of these
      IGFBP-3 binding proteins. Human serum was fractionated over an IGFBP-3 affinity
      column, and a 70-kDa protein was eluted, sequenced, and identified (through
      database searching and Western immunoblot) as human Tf. Tf bound IGFBP-3 but had
      negligible affinity to the other five IGFBPs, and iron-saturated holo-Tf bound
      IGFBP-3 more avidly than unsaturated Tf. Biosensor interaction analysis confirmed
      that this interaction is specific and sensitive, with a high association rate
      similar to IGF-I, and suggested that binding occurs in the vicinity of the IGFBP
      3 nuclear localization site. As an independent confirmation of this interaction,
      using a yeast two-hybrid system, we cloned Tf from a human liver complementary
      DNA library as an IGFBP-3 protein partner. Tf treatment blocked IGFBP-3-induced
      cell proliferation in bladder smooth muscle cells, and IGFBP-3-induced apoptosis
      in prostate cancer cells. In summary, we have employed a combination of
      techniques to demonstrate that Tf specifically binds IGFBP-3, and we showed that
      this interaction has important physiological effects on cellular events.

PMID- 11297623
TI  - Impairment of spermatogonial development and spermiation after testosterone
      induced gonadotropin suppression in adult monkeys (Macaca fascicularis).
AB  - Human male hormonal contraceptive regimens do not consistently induce
      azoospermia, and the basis of this variable response is unclear. This study used
      nine adult macaque monkeys (Macaca fascicularis) given testosterone (T) implants
      for 20 weeks to study changes in germ cell populations in relation to sperm
      output. Germ cell numbers were determined using the optical disector
      stereological method. Four animals achieved consistent azoospermia (azoo group),
      whereas five animals did not (nonazoo group). T-induced gonadotropin suppression
      in all animals decreased A pale (Ap) spermatogonia to 45% of baseline within 2
      weeks, leading to decreased B spermatogonia (32--38%) and later germ cells (20-
      30%) after 14 and 20 weeks. Though the reduction in later germ cell types could
      be primarily attributed to the loss of spermatogonia, the data suggested that
      some cells were lost during the spermatocyte and spermatid phase of development.
      B spermatogonial number was more markedly suppressed in azoospermic animals,
      compared with the nonazoo group, as was the conversion ratio between Ap and B
      spermatogonia. Abnormal retention of elongated spermatids (failed spermiation)
      was also prominent in some animals after long-term T administration. We conclude
      that: 1) the variable suppression of sperm output is attributed to the degree of
      inhibition of germ cell development from type B spermatogonia onwards, and this
      is related to the degree of FSH suppression; and 2) inhibition of Ap and B
      spermatogonial development and of spermiation are the major defects caused by
      long-term T administration to monkeys.

PMID- 11297626
TI  - Fractures after long-term alendronate therapy.

PMID- 11297624
TI  - Angiogenic growth factor messenger ribonucleic acids in uterine natural killer
      cells.
AB  - Angiogenesis is essential for endometrial growth and repair, and disruption of
      this process may lead to common disorders of women, including menorrhagia and
      endometriosis. In pregnancy, failure of the endometrial spiral arterioles to
      undergo remodeling leads to preeclampsia. Here we report that in addition to
      vascular endothelial growth factor A (VEGF-A), human endometrium expresses
      messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor
      (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors
      VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed
      during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was
      found in uterine nature killer cells in secretory phase endometrium and for Ang2
      mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL
      15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells.
      Conditioned medium from decidual NK cells did not induce human umbilical vein
      endothelial cell apoptosis. These results indicate that human endometrium
      expresses a wide range of angiogenic growth factors and that uterine nature
      killer cells may play an important role in the abnormal endometrial angiogenesis
      that underlies a range of disorders affecting women.

PMID- 11297627
TI  - Aromatase inhibitors in pubertal boys: clinical implications.

PMID- 11297630
TI  - Practical classification of prolactinomas for clinical use.

PMID- 11297632
TI  - Physical performance in growth hormone- deficient adults.

PMID- 11297633
TI  - Optimal range of plasma concentration of true 1-84 parathyroid hormone in
      patients on maintenance dialysis.

PMID- 11297635
TI  - What are "normal" testosterone levels for women?

PMID- 11297637
TI  - Citation of "validation" references for sphygmocor-based estimates of central
      aortic blood pressure.

PMID- 11297638
TI  - Long-term consequences of castration in men.

PMID- 11297643
TI  - Health and housing: a lasting relationship.

PMID- 11297644
TI  - A widening horizon for European public health practice.

PMID- 11297639
TI  - Homocysteine, folate, vitamin B12, and transcobalamins in patients undergoing
      successive hypo- and hyperthyroid states.

PMID- 11297645
TI  - A basic glossary of vaccinology.

PMID- 11297646
TI  - Suicide in doctors: a study of risk according to gender, seniority and specialty
      in medical practitioners in England and Wales, 1979-1995.
AB  - STUDY OBJECTIVE: To investigate the suicide risk of doctors in England and Wales,
      according to gender, seniority and specialty. DESIGN: Retrospective cohort study.
      Suicide rates calculated by gender, age, specialty, seniority and time period.
      Standardised mortality ratios calculated for suicide (1991-1995), adjusted for
      age and sex. SETTING: England and Wales. SUBJECTS: Doctors in the National Health
      Service who died by suicide between 1979 and 1995, identified by death
      certificates. Population at risk based on Department of Health manpower data.
      MAIN RESULTS: Two hundred and twenty three medical practitioners in the National
      Health Service who died by suicide or undetermined cause were identified. The
      annual suicide rates in male and female doctors were 19.2 and 18.8 per 100 000
      respectively. The suicide rate in female doctors was higher than in the general
      population (SMR 201.8; 95% CI 99.7, 303.9), whereas the rate in male doctors was
      less than that of the general population (SMR 66.8; 95% CI 46.6, 87.0). The
      difference between the mortality ratios of the female and male doctors was
      statistically significant (p=0.01), although the absolute suicide risk was
      similar in the two genders. There were significant differences between
      specialties (p=0.0001), with anaesthetists, community health doctors, general
      practitioners and psychiatrists having significantly increased rates compared
      with doctors in general hospital medicine. There were no differences with regard
      to seniority and time period. CONCLUSIONS: There is an increased risk of suicide
      in female doctors, but male doctors seem to be at less risk than men in the
      general population. The excess risk of suicide in female doctors highlights the
      need to tackle stress and mental health problems in doctors more effectively. The
      risk requires particular monitoring in the light of the very large increase in
      the numbers of women entering medicine.

PMID- 11297647
TI  - Relative contribution of early life and adult socioeconomic factors to adult
      morbidity in the Whitehall II study.
AB  - STUDY OBJECTIVE: To determine the relative contribution of adult compared with
      early life socioeconomic status as predictors of morbidity attributable to
      coronary heart disease (CHD), chronic bronchitis and depression in the Whitehall
      II study of British civil servants. DESIGN: Prospective observational study with
      mean 5.3 years (range 3.7-7.6) follow up. SETTING: 20 civil service departments
      originally located in London. PARTICIPANTS: 6895 male and 3413 female office
      based civil servants aged 35-55 years at baseline. OUTCOME MEASURES: New cases at
      follow up of CHD, chronic bronchitis and depression defined using validated
      questionnaires. MAIN RESULTS: Employment grade was inversely associated with CHD,
      chronic bronchitis and depression in men (odds ratio per unit decrease in grade
      1.30, 1.44 and 1.20 respectively). Employment grade was strongly related to
      father's social class. Chronic bronchitis, in women, and depression, in men, were
      more common among those with fathers of higher social class. When mutual
      adjustment was made for father's social class, grade at entry to the civil
      service and current grade, the strongest effects on adult morbidity were found
      for current grade. Among participants in whom neither parent had died < or =70
      years of age the inverse association with adult SES was maintained. CONCLUSIONS:
      Adult socioeconomic status was a more important predictor of morbidity
      attributable to coronary disease, chronic bronchitis and depression than measures
      of social status earlier in life. In this population, the importance of social
      circumstances early in life may be in the way they influence employment and
      social position and thus exposures in adult life.

PMID- 11297648
TI  - Prognostic factors in women with breast cancer: distribution by socioeconomic
      status and effect on differences in survival.
AB  - STUDY OBJECTIVE: To quantify and investigate differences in survival from breast
      cancer between women resident in affluent and deprived areas and define the
      contribution of underlying factors to this variation. DESIGN: Analysis of two
      datasets relating to breast cancer patients in Scotland: (1) population-based
      cancer registry data; (2) a subset of cancer registration records supplemented by
      abstraction of prognostic variables (stage, node status, tumour size, oestrogen
      receptor (ER) status, type of surgery, use of radiotherapy and use of adjuvant
      systemic therapy) from medical records. SETTING: Scotland. PATIENTS: (1) Cancer
      registration data on 21,751 women aged under 85 years diagnosed with primary
      breast cancer between 1978 and 1987; (2) national clinical audit data on 2035
      women aged under 85 years diagnosed with primary breast cancer during 1987 for
      whom adequate medical records were available. MAIN RESULTS: Survival differences
      of 10% between affluent and deprived women were observed in both datasets, across
      all age groups. In the audit dataset, the distribution of ER status varied by
      deprivation group (65% ER positive in affluent group v 48% ER positive in
      deprived group; under 65 age group). Women aged under 65 with non-metastatic
      disease were more likely to have breast conservation than a mastectomy if they
      were affluent (45%) than deprived (32%); the affluent were more likely to receive
      endocrine therapy (65%) than the deprived (50%). However, these factors accounted
      for about 20% of the observed difference in survival between women resident in
      affluent and deprived areas. CONCLUSIONS: Deprived women with breast cancer have
      poorer outcomes than affluent women. This can only partly be explained by
      deprived women having more ER negative tumours than affluent women. Further
      research is required to identify other reasons for poorer outcomes in deprived
      women, with a view to reducing these survival differences.

PMID- 11297649
TI  - Long working hours and risk for hypertension in Japanese male white collar
      workers.
AB  - STUDY OBJECTIVE: To evaluate the association of long working hours with the risk
      for hypertension. DESIGN: A five year prospective cohort study. SETTING: Work
      site in Osaka, Japan. PARTICIPANTS: 941 hypertension free Japanese male white
      collar workers aged 35-54 years were prospectively examined by serial annual
      health examinations. Men in whom borderline hypertension and hypertension were
      found during repeated surveys were defined as incidental cases of borderline
      hypertension and hypertension. MAIN RESULTS: 336 and 88 men developed
      hypertension above the borderline level and definite hypertension during the 3940
      and 4531 person years, respectively. After controlling for potential predictors
      of hypertension, the relative risk for hypertension above the borderline level,
      compared with those who worked < 8.0 hours per day, was 0.63 (95% confidence
      intervals (CI): 0.43, 0.91) for those who worked 10.0-10.9 hours per day and 0.48
      (95% CI: 0.31, 0.74) for those who worked > or = 11.0 hours per day. The relative
      risk for definite hypertension, compared with those who worked < 8.0 hours per
      day, was 0.33 (95% CI: 0.11, 0.95) for those who worked > or = 11.0 hours per
      day. The multivariate adjusted slopes of diastolic blood pressure (DBP) and mean
      arterial blood pressure (MABP) during five years of follow up decreased as
      working hours per day increased. From the multiple regression analyses, working
      hours per day remained as an independent negative factor for the slopes of
      systolic blood pressure, DBP, and MABP. CONCLUSIONS: These results indicate that
      long working hours are negatively associated with the risk for hypertension in
      Japanese male white collar workers.

PMID- 11297650
TI  - Survival after initial hospitalisation for heart failure: a multilevel analysis
      of patients in Swedish acute care hospitals.
AB  - STUDY OBJECTIVE: Although national variation in short-term prognosis (that is, 30
      day mortality) after a patient's first hospitalisation for heart failure may
      depend on individual differences between patients, dissimilarities in hospital
      practices may also influence prognosis. This study, therefore, sought to
      disentangle patient determinants from institutional factors that might explain
      such variation. DESIGN: A multilevel logistic regression modelling was performed
      with patients (1st level) nested in hospitals (2nd level). Institutional effects
      (that is, 2nd level variance and intra-hospital correlation) were calculated
      unadjusted and adjusted for specific patient (that is, age and previous diseases)
      and institutional (that is, size of hospital) characteristics. Patients were
      followed up until death or 30 days from hospital admission. SETTING: Hospitals in
      Sweden. PATIENTS: The study identified all the 20420 men and 17923 women (ages 65
      to 85) admitted to the 90 acute care hospitals in Sweden during the period 1992
      1995 for their first hospitalisation attributable to heart failure. MAIN RESULTS:
      Patient age and previous diseases (particularly senile dementia) were major
      determinants of impaired prognosis. Institutional factors explained only 1.6% and
      2.3% of the total variation in 30 day mortality in men and women, respectively.
      These modest institutional effects remained after adjusting for patient age and
      previous diseases, but were in part explained by hospital size. CONCLUSIONS:
      National variation in short-term prognosis after an initial hospitalisation for
      heart failure was mainly explained by differences between patients, with hospital
      factors playing a minor part. Of the latter, hospital size seemed to emerge as
      one determinant (that is, the greater the number of patients, the better the
      individual prognosis).

PMID- 11297651
TI  - Housing tenure and car access: further exploration of the nature of their
      relations with health in a UK setting.

PMID- 11297652
TI  - Mismatch between perceived and actual overweight in diabetic and non-diabetic
      populations: a comparative study of South Asian and European women.

PMID- 11297653
TI  - Smoking in adolescence and young adulthood and mortality in later life:
      prospective observational study.

PMID- 11297654
TI  - Abortion and breast cancer: a case-control record linkage study.

PMID- 11297655
TI  - Incidence of ocular melanoma in the general population and in glaucoma patients.

PMID- 11297656
TI  - Social circumstances in childhood and cardiovascular disease mortality:
      prospective observational study of Glasgow University students.

PMID- 11297657
TI  - Rationalising chances of success in intersectoral health policy making.
AB  - OBJECTIVE: It is generally accepted that a wide range of factors determine the
      health of a population, many of which are beyond the remit of the Ministry of
      Health. The aim of intersectoral health policy is to influence these factors.
      Success depends on a multi-stage process. This paper aims to provide support for
      the first stage of this process in the form of a quick scan for appraising the
      feasibility of intersectoral health policy. DESIGN: The content of the quick scan
      for intersectoral health policy was derived from a literature review. To
      determine the usefulness of this quick scan, the study looked at two examples in
      the policy sectors of education and safety. MAIN RESULTS: The quick scan
      distinguishes between three factors: (1) the availability of evidence, (2) the
      degree of support, and (3) the availability of tools for implementation. The
      quick scan made it possible to review the two policy sectors systematically in a
      relatively short time and to obtain sufficient information for priority setting
      in intersectoral health policy. The examples in this paper suggest that
      intersectoral health policy for community safety is more feasible than
      intersectoral policy for psychosocial problems in secondary education. However,
      specific information is required for a more precise assessment of feasibility.
      CONCLUSIONS: There are many ways of improving health through intersectoral health
      policy. The proposed quick scan may provide systematic support for setting
      priorities before developing policies of this kind.

PMID- 11297658
TI  - Methods used to maintain a high level of participant involvement in a clinical
      trial.
AB  - OBJECTIVES: To describe the strategies adopted to maintain high level
      participation throughout a community based clinical trial, and the reasons given
      by participants for why they participated in the study. DESIGN: Observational
      study. SETTING: Community based clinical trial in Melbourne, Australia that ran
      for 68 weeks and involved 2811 community based individuals from 600 families. A
      high level of commitment was required of the families; each participant completed
      a Health Diary each week of the 68 week study, as well as answering numerous
      other questionnaires, and providing faecal and blood samples. MAIN RESULTS: Only
      41 of the 600 families withdrew from the study; the majority of these families
      withdrew because they sold their home and moved from the study area. The
      completion rate of Health Diaries averaged 90.7% over the 68 weeks of data
      collection. Of the 559 families who completed the study, 524 (93.7%) completed
      the Participation Questionnaire. The statement that received the highest rating
      for why families enrolled in the study was they thought the study was researching
      an important community issue. The statements that received the highest ratings
      for why families continued to participate in the study was the family being kept
      well informed about the study's progress and that the study was well run.
      CONCLUSIONS: The low numbers of withdrawals and the high level of participation
      throughout the study suggests the strategies of (a) having a non-aggressive
      recruitment method, (b) maintaining regular contact with the participants and (c)
      ensuring participants were kept well informed of the study's progress and
      constantly encouraged to continue participation were successful. The results also
      suggest people involve themselves in research because they perceive it to be of
      value to the community, not simply for personal gain. They indicated that they
      maintained their participation because it was a well run study and they were kept
      well informed throughout the study.

PMID- 11297659
TI  - What is the difference between controlling for mean versus median income in
      analyses of income inequality?

PMID- 11297660
TI  - Are cities becoming more unhealthy? An analysis of mortality rates in Belfast and
      Dublin between 1981 and 1991 to illustrate a methodological difficulty with
      ecological studies.

PMID- 11297662
TI  - Use of health services by prison inmates: comparisons with the community.

PMID- 11297661
TI  - Large decline in injecting drug use in Amsterdam, 1986-1998: explanatory
      mechanisms and determinants of injecting transitions.
AB  - OBJECTIVES: To study community wide trends in injecting prevalence and trends in
      injecting transitions, and determinants. DESIGN: Open cohort study with follow up
      every four months (Amsterdam Cohort Study). Generalised estimating equations were
      used for statistical analysis. SETTING: Amsterdam has adopted a harm reduction
      approach as drug policy. PARTICIPANTS: 996 drug users who were recruited from
      1986 to 1998, mainly at methadone programmes, who paid 13620 cohort visits. MAIN
      RESULTS: The prevalence of injecting decreased exponentially (66% to 36% in four
      to six monthly periods). Selective mortality and migration could maximally
      explain 33% of this decline. Instead, injecting initiation linearly decreased
      (4.1% to 0.7% per visit), cessation exponentially increased (10.0% to 17.1%), and
      relapse linearly decreased (21.3% to 11.8%). Non-injecting cocaine use (mainly
      pre-cooked, comparable to crack) and heroin use strongly increased. Trends were
      not attributable to changes in the study sample. CONCLUSIONS: Harm reduction,
      including large scale needle exchange programmes, does not lead to an increase in
      injecting drug use. The injecting decline seems mainly attributable to ecological
      factors (for example, drug culture and market). Prevention of injecting is
      possible and peer-based interventions may be effective. The consequences of the
      recent upsurge in crack use requires further study.

PMID- 11297663
TI  - Performance of surrogate markers of low birth weight at community level in rural
      India.

PMID- 11297664
TI  - Using subsite coupling to predict signal peptides.
AB  - Given a nascent protein sequence, how can one predict its signal peptide or
      "Zipcode" sequence? This is a first important problem for scientists to use
      signal peptides as a vehicle to find new drugs or to reprogram cells for gene
      therapy. Based on a model that takes into account the coupling effect among some
      key subsites, the so-called [-3, -1, +1] coupling model, a new prediction
      algorithm is developed. The overall rate of correct prediction for 1939 secretory
      proteins and 1440 non-secretary proteins was over 92%. It has not escaped our
      attention that the new method may also serve as a useful tool for helping
      investigate further many unclear details regarding the molecular mechanism of the
      ZIP code protein-sorting system in cells.

PMID- 11297665
TI  - Crystal structures of mutants of Thermus thermophilus IPMDH adapted to low
      temperatures.
AB  - Random mutagenesis on thermophilic 3-isopropylmalate dehydrogenases (IPMDH; EC
      1.1.1.85) produced mutant enzymes which adapt to low temperatures. These mutants
      had higher activity at lower temperatures than the wild-type enzyme without
      losing high thermostability. Here we report three structures of the mutants of
      Thermus thermophilus IPMDH determined by X-ray diffraction which was adapted to a
      low-temperature environment. Two of them have unstable coenzyme binding states
      and the other one probably has a stable substrate binding state. The present
      research suggests that the adaptation is correlated with the binding of either
      coenzyme or the substrate.

PMID- 11297666
TI  - Adaptation of a thermophilic enzyme, 3-isopropylmalate dehydrogenase, to low
      temperatures.
AB  - Random mutagenesis coupled with screening of the active enzyme at a low
      temperature was applied to isolate cold-adapted mutants of a thermophilic enzyme.
      Four mutant enzymes with enhanced specific activities (up to 4.1-fold at 40
      degrees C) at a moderate temperature were isolated from randomly mutated Thermus
      thermophilus 3-isopropylmalate dehydrogenase. Kinetic analysis revealed two types
      of cold-adapted mutants, i.e. k(cat)-improved and K(m)-improved types. The k(cat)
      improved mutants showed less temperature-dependent catalytic properties,
      resulting in improvement of k(cat) (up to 7.5-fold at 40 degrees C) at lower
      temperatures with increased K(m) values mainly for NAD. The K(m)-improved enzyme
      showed higher affinities toward the substrate and the coenzyme without
      significant change in k(cat) at the temperatures investigated (30-70 degrees C).
      In k(cat)-improved mutants, replacement of a residue was found near the binding
      pocket for the adenine portion of NAD. Two of the mutants retained thermal
      stability indistinguishable from the wild-type enzyme. Extreme thermal stability
      of the thermophilic enzyme is not necessarily decreased to improve the catalytic
      function at lower temperatures. The present strategy provides a powerful tool for
      obtaining active mutant enzymes at lower temperatures. The results also indicate
      that it is possible to obtain cold-adapted mutant enzymes with high thermal
      stability.

PMID- 11297667
TI  - A proposed structural model for amyloid fibril elongation: domain swapping forms
      an interdigitating beta-structure polymer.
AB  - We propose a model illustrating how proteins, which differ in their overall
      sequences and structures, can form the propagating, twisted beta-sheet
      conformations, characteristic of amyloids. Some cases of amyloid formation can be
      explained through a "domain swapping" event, where the swapped segment is either
      a beta-hairpin or an unstable conformation which can partially unfold and assume
      a beta-hairpin structure. As in domain swapping, here the swapped beta-hairpin is
      at the edge of the structure, has few (if any) salt bridges and hydrogen bonds
      connecting it to the remainder of the structure and variable extents of buried
      non-polar surface areas. Additionally, in both cases the swapped piece
      constitutes a transient "building block" of the structure, with a high population
      time. Whereas in domain swapping the swapped fragment has been shown to be an
      alpha-helix, loop, strand or an entire domain, but so far not a beta-hairpin,
      despite the large number of cases in which it was already detected, here swapping
      may involve such a structural motif. We show how the swapping of beta-hairpins
      would form an interdigitated, twisted beta-sheet conformation, explaining the
      remarkable high stability of the protofibril in vitro. Such a swapping mechanism
      is attractive as it involves a universal mechanism in proteins, critical for
      their function, namely hinge-bending motions. Our proposal is consistent with
      structural superpositioning of mutational variants. While the overall r.m.s.d.s
      of the wild-type and mutants are small, the proposed hinge-bending region
      consistently shows larger deviations. These larger deviations illustrate that
      this region is more prone to respond to the mutational changes, regardless of
      their location in the sequence or in the structure. Nevertheless, above all, we
      stress that this proposition is hypothetical, since it is based on assumptions
      lacking definitive experimental support.

PMID- 11297668
TI  - Protein docking using continuum electrostatics and geometric fit.
AB  - The computer program DOT quickly finds low-energy docked structures for two
      proteins by performing a systematic search over six degrees of freedom. A novel
      feature of DOT is its energy function, which is the sum of both a Poisson
      Boltzmann electrostatic energy and a van der Waals energy, each represented as a
      grid-based correlation function. DOT evaluates the energy of interaction for many
      orientations of the moving molecule and maintains separate lists scored by either
      the electrostatic energy, the van der Waals energy or the composite sum of both.
      The free energy is obtained by summing the Boltzmann factor over all rotations at
      each grid point. Three important findings are presented. First, for a wide
      variety of protein-protein interactions, the composite-energy function is shown
      to produce larger clusters of correct answers than found by scoring with either
      van der Waals energy (geometric fit) or electrostatic energy alone. Second, free
      energy clusters are demonstrated to be indicators of binding sites. Third, the
      contributions of electrostatic and attractive van der Waals energies to the total
      energy term appropriately reflect the nature of the various types of protein
      protein interactions studied.

PMID- 11297669
TI  - Molecular dynamics study of Ca(2+) binding loop variants of parvalbumin with
      modifications at the "gateway" position.
AB  - The helix-loop-helix (i.e. EF-hand) Ca(2+) ion binding motif is characteristic of
      a large family of high-affinity Ca(2+) ion binding proteins, including the
      parvalbumins and calmodulins. In this paper we describe a set of molecular
      dynamics computations on the major parvalbumin from the silver hake (SHPV-B). In
      all variants examined, both whole protein and fragments thereof, the ninth loop
      residue in the Ca(2+) binding coordination site in the CD helix-loop-helix region
      (the so-called "gateway" residue) has been mutated. The three gateway mutations
      examined are arginine, which has never been found at the gateway position of any
      EF-hand protein, cysteine, which is the residue observed least in natural EF-hand
      sites, and serine, which is the most common (by far) non-acidic residue
      substitution at this position in EF-hand proteins in general, but never in
      parvalbumins. Results of the molecular dynamics simulations indicate that all
      three modifications are disruptive to the integrity of the mutated Ca(2+) binding
      site in the whole parvalbumin protein. In contrast, only the arginine and
      cysteine mutations are disruptive to the integrity of the mutated Ca(2+) binding
      site in the CD fragment of the parvalbumin protein. Surprisingly, the serine
      variant of the CD helix-loop-helix fragment exhibited remarkable stability during
      the entire molecular dynamics simulation, with retention of the Ca(2+) binding
      site. These results indicate that there are no inherent problems (for Ca(2+) ion
      binding) associated with the sequence of the CD helix-loop-helix fragment that
      precludes the incorporation of serine at the gateway position. Since the CD site
      is totally disrupted in the whole protein serine variant, this indicates that the
      Ca(2+) ion binding deficiencies are most likely related to the unique interaction
      that exists between the paired EF-hands in the whole protein. Our theoretical
      results correlate well with previous studies on engineered EF-hand proteins and
      with all of our experimental evidence on the silver hake parvalbumin.

PMID- 11297670
TI  - Are the parameters of various stabilization factors estimated from mutant human
      lysozymes compatible with other proteins?
AB  - The various factors which contribute to protein stability have been extensively
      examined using mutant proteins, but the same kinds of substitutions have given
      different results depending on the substitution sites. Recently, the
      contributions of some stabilization factors have been quantitatively derived as
      parameters by a unique equation, considering the conformational changes due to
      the mutations using mutant human lysozymes [Funahashi et al. (1999) Protein ENG:
      12, 841-850]. To evaluate these parameters estimated from the mutant human
      lysozymes, stability-structure datasets for the mutant T4 lysozymes were
      selected. The stabilities for the mutant T4 lysozymes could be roughly estimated
      using these parameters. Notable differences between the estimated and
      experimental stabilities were caused by the uncertainty in part of the structures
      due to some Arg and Lys residues fluctuating on the surface of the T4 lysozyme.
      Excluding these atoms from the estimation gave a good correlation between the
      estimated and experimental stabilities. These results suggest that the parameters
      of the various stabilization factors derived from the mutant human lysozymes are
      compatible with the mutant T4 lysozymes, although they should be improved with
      respect to some points using more information.

PMID- 11297671
TI  - Asn to Lys mutations at three sites which are N-glycosylated in the mammalian
      protein decrease the aggregation of Escherichia coli-derived erythropoietin.
AB  - Erythropoietin (EPO) derived from Escherichia coli is unstable to elevated
      temperature and tends to aggregate with time, making it unsuitable for high
      resolution structure analysis. The mammalian EPO contains about 40% carbohydrate,
      which makes this protein more stable and less prone to aggregate than non
      glycosylated E.coli-derived EPO, but makes it unsuitable for high-resolution
      analysis owing to its size and flexibility. In an attempt to decrease the
      aggregation of E.coli-derived EPO, the three asparagine residues at positions 24,
      38 and 83 were mutated to lysine residues. In the native protein, these residues
      are the sites of N-linked glycosylation, which suggests that they should be
      located on the surface of the protein and should not be involved in interactions
      in the hydrophobic protein core. Therefore, the substitution of basic amino acids
      for these neutral asparagine residues is not expected to affect the protein
      structure, but should increase the isoelectric point of the protein and its net
      positive charge, decreasing its tendency to aggregate at or below neutral pH due
      to electrostatic interactions. No apparent alterations in receptor binding, as
      determined by both cell-surface receptor competition assay and in vitro receptor
      dimerization experiments, were observed when these mutations were introduced into
      the EPO sequence. However, this mutant protein displayed a significant increase
      in stability to heat treatment and to storage, relative to the wild-type
      molecule. This resulted in a greater number of observable cross peaks in the
      mutant EPO in 2D NOESY experiments. However, the mutant was similar to the wild
      type in stability when urea was used as a denaturant. This indicates that the
      introduced mutations resulted in a decrease in aggregation with heating or with
      prolonged incubation at ambient temperature, without changing the conformational
      stability or the receptor binding affinity of the mutant protein. This approach
      of placing charged residues at sites where N-glycosylation occurs in vivo could
      be applied to other systems as well.

PMID- 11297672
TI  - Functional interactions in internal translation initiation directed by viral and
      cellular IRES elements.

PMID- 11297673
TI  - Non-structural proteins 2 and 3 interact to modify host cell membranes during the
      formation of the arterivirus replication complex.
AB  - The replicase polyproteins of equine arteritis virus (EAV; family Arteriviridae,
      order Nidovirales) are processed by three viral proteases to yield 12 non
      structural proteins (nsps). The nsp2 and nsp3 cleavage products have previously
      been found to interact, a property that allows nsp2 to act as a co-factor in the
      processing of the downstream part of the polyprotein by the nsp4 protease.
      Remarkably, upon infection of Vero cells, but not of BHK-21 or RK-13 cells, EAV
      nsp2 is now shown to be subject to an additional, internal, cleavage. In Vero
      cells, approximately 50% of nsp2 (61 kDa) was cleaved into an 18 kDa N-terminal
      part and a 44 kDa C-terminal part, most likely by a host cell protease that is
      absent in BHK-21 and RK-13 cells. Although the functional consequences of this
      additional processing step are unknown, the experiments in Vero cells revealed
      that the C-terminal part of nsp2 interacts with nsp3. Most EAV nsps localize to
      virus-induced double-membrane structures in the perinuclear region of the
      infected cell, where virus RNA synthesis takes place. It is now shown that, in an
      expression system, the co-expression of nsp2 and nsp3 is both necessary and
      sufficient to induce the formation of double-membrane structures that strikingly
      resemble those found in infected cells. Thus, the nsp2 and nsp3 cleavage products
      play a crucial role in two processes that are common to positive-strand RNA
      viruses that replicate in mammalian cells: controlled proteolysis of replicase
      precursors and membrane association of the virus replication complex.

PMID- 11297674
TI  - Identification of an immunodominant epitope in the C terminus of glycoprotein 5
      of porcine reproductive and respiratory syndrome virus.
AB  - Glycoprotein 5 (GP(5)) is the major glycoprotein of porcine reproductive and
      respiratory syndrome virus (PRRSV). Expression of GP(5) has been improved by
      removing the transmembrane regions. Vectors were constructed encoding complete
      GP(5) plus three mutants: GP(5) Ns (residues 28--201), GP(5)[30--67] (residues 30
      -67) and GP(5)[30--201] (residues 30--67/130--201). The three deletion mutants
      were expressed at levels 20--30 times higher than complete GP(5). GP(5)[30--201]
      was well recognized in ELISA or immunoblotting by a collection of pig sera. All
      the fragments were tested for the generation of MAbs, but only the polyhistidine
      tagged fragment GP(5)[30--201]H elicited an antibody response sufficient to
      produce MABS: The two MAbs were positive for PRRSV in ELISA and immunoblotting,
      but negative for virus neutralization. MAb 4BE12 reacted with residues 130--170
      and MAb 3AH9 recognized residues 170--201. This region was recognized strongly in
      immunoblotting by a collection of infected-pig sera. These results indicate
      diagnostic potential for this epitope.

PMID- 11297675
TI  - Phylogenetic analyses confirm the high prevalence of hepatitis C virus (HCV) type
      4 in the Seine-Saint-Denis district (France) and indicate seven different HCV-4
      subtypes linked to two different epidemiological patterns.
AB  - Hepatitis C virus (HCV) has been classified into six clades as a result of high
      genetic variability. In the Seine-Saint-Denis district of north-east Paris, the
      prevalence of HCV-4, which usually infects populations from Africa or the Middle
      East, is twice as high as that recorded for the whole of continental France (10.2
      versus 4.5%). Although the pathogenicity of HCV-4 remains unknown, resistance of
      HCV-4 to therapy appears to be similar to that observed for HCV-1. In order to
      characterize the epidemiology of HCV-4 in Paris, sequences of the non-structural
      5B gene (332 bp) were obtained from 38 HCV-4-infected patients. Extensive
      phylogenetic analyses indicated seven different HCV-4 subtypes. Moreover,
      phylogenetic tree topologies clearly distinguished two epidemiological profiles.
      The first profile (52.6% of patients) reflects the intra-suburban emergence of
      two distinct HCV-4 subclades occurring mainly among intravenous drug users (65%
      of patients). The second profile shows six subclades [HCV-4a, -4f, -4h, -4k, 
      4a(B) and a new sequence] and accounts for patients from Africa (Egypt and sub
      Saharan countries) who have unknown risk factors (77.8% of patients) and in whom
      no recent diffusion of HCV-4 is evident. This study indicates the high diversity
      of HCV-4 and the extension of HCV-4a and -4d subclades among drug users in
      FRANCE:

PMID- 11297676
TI  - Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not
      a proteolytic reaction, but a novel translational effect: a putative ribosomal
      'skip'.
AB  - The 2A region of the aphthovirus foot-and-mouth disease virus (FMDV) polyprotein
      is only 18 aa long. A 'primary' intramolecular polyprotein processing event
      mediated by 2A occurs at its own C terminus. FMDV 2A activity was studied in
      artificial polyproteins in which sequences encoding reporter proteins flanked the
      2A sequence such that a single, long, open reading frame was created. The self
      processing properties of these artificial polyproteins were investigated and the
      co-translational 'cleavage' products quantified. The processing products from our
      artificial polyprotein systems showed a molar excess of 'cleavage' product N
      terminal of 2A over the product C-terminal of 2A. A series of experiments was
      performed to characterize our in vitro translation systems. These experiments
      eliminated the translational or transcriptional properties of the in vitro
      systems as an explanation for this imbalance. In addition, the processing
      products derived from a control construct encoding the P1P2 region of the human
      rhinovirus polyprotein, known to be proteolytically processed, were quantified
      and found to be equimolar. Translation of a construct encoding green fluorescent
      protein (GFP), FMDV 2A and beta-glucuronidase, also in a single open reading
      frame, in the presence of puromycin, showed this antibiotic to be preferentially
      incorporated into the [GFP2A] translation product. We conclude that the discrete
      translation products from our artificial polyproteins are not produced by
      proteolysis. We propose that the FMDV 2A sequence, rather than representing a
      proteolytic element, modifies the activity of the ribosome to promote hydrolysis
      of the peptidyl(2A)-tRNA(Gly) ester linkage, thereby releasing the polypeptide
      from the translational complex, in a manner that allows the synthesis of a
      discrete downstream translation product to proceed. This process produces a
      ribosomal 'skip' from one codon to the next without the formation of a peptide
      bond.

PMID- 11297678
TI  - Roles of the H-2D(b) and H-K(b) genes in resistance to persistent Theiler's
      murine encephalomyelitis virus infection of the central nervous system.
AB  - Theiler's murine encephalomyelitis virus, a member of the Picornaviridae family,
      persists in the spinal cord of susceptible strains of mice. Resistant strains of
      mice, such as the H-2(b) strain, clear the virus infection after an acute
      encephalomyelitis. The H-2D locus, but not the H-2K locus, has a major effect on
      this resistance, although both loci code for MHC class I molecules with similar
      general properties. For the present work, we rendered susceptible H-2(q) FVB/N
      mice transgenic for either the H-2D(b)gene, the H-2K(b) gene or a chimeric H
      2D(b)/K(b) gene in which the exons encoding the peptide-binding groove of the H
      2K(b) gene have been replaced by those of the H-2D(b)gene. Mice transgenic for
      either the H-2D(b)gene or the chimeric H-2D(b)/K(b) gene were significantly more
      resistant to persistent virus infection than mice transgenic for the H-2K(b)
      gene, suggesting that the difference in the effects of the H-2D(b)gene and the H
      2K(b) gene are due to the nature of the peptides presented by these class I
      molecules.

PMID- 11297677
TI  - The 'cleavage' activities of foot-and-mouth disease virus 2A site-directed
      mutants and naturally occurring '2A-like' sequences.
AB  - The 2A/2B cleavage of aphtho- and cardiovirus 2A polyproteins is mediated by
      their 2A proteins 'cleaving' at their own C termini. We have analysed this
      activity using artificial reporter polyprotein systems comprising green
      fluorescent protein (GFP) linked via foot-and-mouth disease virus (FMDV) 2A to
      beta-glucuronidase (GUS) -- forming a single, long, open reading frame. Analysis
      of the distribution of radiolabel showed a high proportion of the in vitro
      translation products (approximately 90%) were in the form of the 'cleavage'
      products GUS and [GFP2A]. Alternative models have been proposed to account for
      the 'cleavage' activity: proteolysis by a host-cell proteinase, autoproteolysis
      or a translational effect. To investigate the mechanism of this cleavage event
      constructs encoding site-directed mutant and naturally occurring '2A-like'
      sequences were used to program in vitro translation systems and the gel profiles
      analysed. Analysis of site-directed mutant 2A sequences showed that 'cleavage'
      occurred in constructs in which all the candidate nucleophilic residues were
      substituted -- with the exception of aspartate-12. This residue is not, however,
      conserved amongst all functional '2A-like' sequences. '2A-like' sequences were
      identified within insect virus polyproteins, the NS34 protein of type C
      rotaviruses, repeated sequences in Trypanosoma spp. and a eubacterial alpha
      glucosiduronasesequence(Thermatoga maritima aguA). All of the 2A-like sequences
      analysed were active (to various extents), other than the eubacterial alpha
      glucosiduronase 2A-like sequence. This method of control of protein biogenesis
      may well not, therefore, be confined to members of the PICORNAVIRIDAE: Taken
      together, these data provide additional evidence that neither FMDV 2A nor '2A
      like' sequences are autoproteolytic elements.

PMID- 11297679
TI  - Molecular intermediates of fitness gain of an RNA virus: characterization of a
      mutant spectrum by biological and molecular cloning.
AB  - The mutant spectrum of a virus quasispecies in the process of fitness gain of a
      debilitated foot-and-mouth disease virus (FMDV) clone has been analysed. The
      mutant spectrum was characterized by nucleotide sequencing of three virus genomic
      regions (internal ribosome entry site; region between the two AUG initiation
      codons; VP1-coding region) from 70 biological clones (virus from individual
      plaques formed on BHK-21 cell monolayers) and 70 molecular clones (RT--PCR
      products cloned in E. coli). The biological and molecular clones provided
      statistically indistinguishable definitions of the mutant spectrum with regard to
      the distribution of mutations among the three genomic regions analysed and with
      regard to the types of mutations, mutational hot-spots and mutation frequencies.
      Therefore, the molecular cloning procedure employed provides a simple protocol
      for the characterization of mutant spectra of viruses that do not grow in cell
      culture. The number of mutations found repeated among the clones analysed was
      higher than expected from the mean mutation frequencies. Some components of the
      mutant spectrum reflected genomes that were dominant in the prior evolutionary
      history of the virus (previous passages), confirming the presence of memory
      genomes in virus quasispecies. Other components of the mutant spectrum were
      genomes that became dominant at a later stage of evolution, suggesting a
      predictive value of mutant spectrum analysis with regard to the outcome of virus
      evolution. The results underline the observation that greater insight into
      evolutionary processes of viruses may be gained from detailed clonal analyses of
      the mutant swarms at the sequence level.

PMID- 11297680
TI  - Comparison of capsid sequences from human and animal astroviruses.
AB  - We have sequenced the genomic 3'-end, including the structural gene, of human
      astrovirus (HAstV) serotype 7 and morphologically related viruses infecting pig
      (PAstV), sheep (OAstV) and turkey (TAstV-1). These sequences were compared with
      corresponding astrovirus sequences available in the nucleic acid databases,
      including sequences of the seven other HAstV serotypes, two other avian
      astroviruses (TAstV-2 and avian nephritis virus) and astrovirus from cat (FAstV).
      A 35 nt stem-loop motif near the 3'-end of the genome, previously described as
      being highly conserved, was present in all of the astroviruses except TAstV-2. In
      the N-terminal half of the capsid precursor protein, there were several short
      conserved peptide motifs. Otherwise the capsid proteins of astroviruses infecting
      different hosts were highly divergent. Calculation of genetic distances revealed
      that the distance between FAstV and HAstV is comparable to the largest distances
      between different HAstV serotypes. Higher similarities between the HAstV, FAstV
      and PAstV capsid sequences suggest interspecies transmissions involving humans,
      cats and pigs relatively recently in the evolutionary history of astroviruses.

PMID- 11297681
TI  - Differential processing and presentation of the H-2D(b)-restricted epitope from
      two different strains of influenza virus nucleoprotein.
AB  - The influenza virus strains A/NT/60/68 and A/PR/8/34 both have an immunodominant
      D(b)-restricted epitope in their nucleoprotein (NP) at amino acid residues 366
      374, with two amino acid differences between the epitopes. Cross-reactive
      cytotoxic T lymphocytes (CTLs) were generated by priming mice with the influenza
      virus A/NT/60/68 NP and restimulating in vitro with influenza virus A/PR/8/34.
      CTLs that gave high levels of specific lysis recognized target cells infected
      with either strain of influenza virus with similar efficiency. Surprisingly, when
      target cells were infected with recombinant vaccinia viruses (VV) expressing the
      two different NPs, presentation of the D(b)-restricted epitope from the
      A/NT/60/68 NP was extremely poor, whereas presentation of the equivalent epitope
      from the A/PR/8/34 NP was as efficient as in influenza virus-infected cells. This
      difference was observed in spite of the fact that the two NP sequences show 94%
      identity at the amino acid sequence level. Experiments with additional cross
      reactive CTL cell lines which recognized target cells less efficiently revealed a
      similar difference in presentation between the two NP epitopes in influenza virus
      infected cells and showed a difference in the efficiency of presentation of the
      D(b)-restricted epitope from the two NP molecules independent of VV infection.
      The results show that two equivalent epitopes in highly similar proteins are
      processed with very different efficiency, even though they are both
      immunodominant epitopes. They also suggest that the previously described
      inhibition of antigen presentation by VV is a general, non-specific effect, which
      is more apparent for epitopes that are processed and presented less efficiently.

PMID- 11297682
TI  - Nucleotides at the extremities of the viral RNA of influenza C virus are involved
      in type-specific interactions with the polymerase complex.
AB  - Influenza A and C viruses share common sequences in the terminal noncoding
      regions of the viral RNA segments. Differences at the 5'- and 3'-ends exist,
      however, that could contribute to the specificity with which the
      transcription/replication signals are recognized by the cognate polymerase
      complexes. Previously, by making use of a transient expression system for the
      transcription and replication of a reporter RNA template bearing either type A or
      type C extremities, it was shown that a type C RNA template is transcribed and
      replicated with equal efficiency by either the type A or the type C polymerase
      complex, whereas a type A RNA template is less efficiently transcribed and
      replicated by the type C polymerase complex than by the type A complex. To
      explore the contribution of the nucleotides at the extremities of the RNAs to
      this type-specificity, the effect of mutations introduced either alone or in
      combination at nucleotide 5 at the 3'-end and at nucleotides 3', 6' or 8' at the
      5'-end of type A or C RNA templates were studied in the presence of either the
      type A or the type C polymerase complex. The results indicate that the nature of
      nucleotides 5 and 6' contribute to type-specificity. Moreover, these results
      underline the importance of the base pairing between nucleotide 3' and 8' at the
      5'-end of the RNA. Thus, it could be suggested that the nature of the nucleotides
      as well as the stability of the secondary structure at the extremities of the
      viral RNA are important determinants of type-specificity.

PMID- 11297683
TI  - The sites for fatty acylation, phosphorylation and intermolecular disulphide bond
      formation of influenza C virus CM2 protein.
AB  - The sites for fatty acylation, disulphide bond formation and phosphorylation of
      influenza C virus CM2 were investigated by site-specific mutagenesis. Cysteine 65
      in the cytoplasmic tail was identified as the site for palmitoylation. Removal of
      one or more of three cysteine residues in the ectodomain showed that all of
      cysteines 1, 6 and 20 can participate in the formation of disulphide-linked
      dimers and/or tetramers, although cysteine 20 may play the most important role in
      tetramer formation. Furthermore, it was found that serine 78, located within the
      recognition motifs for mammary gland casein kinase and casein kinase I, is the
      predominant site for phosphorylation, although serine 103 is phosphorylated to a
      minor extent by proline-dependent protein kinase. The effects of acylation and
      phosphorylation on the formation of disulphide-linked oligomers were also
      studied. The results showed that, while palmitoylation has no role in oligomer
      formation, phosphorylation accelerates tetramer formation without influencing
      dimer formation. CM2 mutants defective in acylation, phosphorylation or
      disulphide bond formation were all transported to the cell surface, suggesting
      that none of these modifications is required for proper oligomerization. When
      proteins solubilized in detergent were analysed on sucrose gradients, however,
      the mutant lacking cysteines 1, 6 and 20 sedimented as monomers, raising the
      possibility that disulphide bond formation, although not essential for proper
      oligomerization, may stabilize the CM2 multimer. This was supported by the
      results of chemical cross-linking analysis, which showed that the triple-cysteine
      mutant can form multimers.

PMID- 11297684
TI  - A complex human immunodeficiency virus type 1 A/G/J recombinant virus isolated
      from a seronegative patient with AIDS from Benin, West Africa.
AB  - A human immunodeficiency virus type 1 (HIV-1(B76)) originating from Benin (West
      Africa) was isolated and characterized. The patient had severe clinical AIDS and
      presented an unusual serological profile. Only one out of five different
      detection assays was able to demonstrate the presence of antibodies to HIV,
      whereas confirmatory assays remained indeterminate. In contrast, both plasma
      viral load and p24 antigen level were unusually high. HIV-1 infection was proved
      by viral RNA and proviral DNA amplification. HIV-1(B76) partially purified lysate
      reacted strongly with all anti-HIV-1-positive sera from the region but B76 plasma
      did not react with subtype A control viral antigen. This patient is likely to
      have had severe acquired immune dysfunction explaining her lack of immunological
      reactivity. Phylogenetic analysis of the genome identified a complex HIV-1 A/G/J
      recombinant. The gag and pol genes, and the majority of nef,are characteristic of
      subtype A; the gag/pol junction, the 3' end of pol, vpu and env genes were
      characteristic of subtype G; vif, vpr and the 5' end of nef were subtype J. In
      addition, part of the HIV-1(B76) genome had considerable sequence similarity with
      the previously described CRF06 cpx (BFP90) isolate. HIV-1(B76) did not exhibit
      any remarkable replication properties or cell tropism in vitro.

PMID- 11297685
TI  - Apoptosis is induced by infectious bursal disease virus replication in
      productively infected cells as well as in antigen-negative cells in their
      vicinity.
AB  - The kinetics of infectious bursal disease virus (IBDV) replication and induction
      of apoptosis were investigated in vitro and in vivo. After infection of chicken
      embryo (CE) cells with IBDV strain Cu-1, the proportion of apoptotic cells
      increased from 5.8% at 4 h post-infection (p.i.) to 64.5% at 48 h p.i. The
      proportion of apoptotic cells correlated with IBDV replication. UV-inactivated
      IBDV particles did not induce apoptosis. Double labelling revealed that, early
      after infection, the majority of antigen-expressing cells were not apoptotic;
      double-labelled cells appeared more frequently at later times. Remarkably,
      apoptotic cells were frequently located in the vicinity of antigen-expressing
      cells. This indicated that an apoptosis-inducing factor(s) might be released by
      cells that replicate IBDV. Since interferon (IFN) production has been
      demonstrated after IBDV infection, IFN was considered to be one of several
      factors. However, supernatants of infected CE cells in which virus infectivity
      had been neutralized were not sufficient to induce apoptosis. Similar results
      were observed in the infected bursae of Fabricius: early after infection, most of
      the cells either showed virus antigens or were apoptotic. Again, double-labelled
      cells appeared more frequently late after infection. This suggests that indirect
      mechanisms might also be involved in the induction of apoptosis in vivo,
      contributing to the rapid depletion of cells in the IBDV-infected bursa.

PMID- 11297686
TI  - The effect of latency-associated transcript on the herpes simplex virus type 1
      latency-reactivation phenotype is mouse strain-dependent.
AB  - Herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) null
      mutants reactivate poorly in the rabbit ocular model. The situation in mice is
      less clear. Reports concluding that LAT null mutants reactivate poorly in the
      mouse explant-induced reactivation (EIR) model are contradicted by a similar
      number of reports of normal EIR of LAT(-) mutants in mice. To determine if the
      EIR phenotype might be mouse strain-dependent we infected BALB/c and Swiss
      Webster mice with LAT(-) or LAT(+) virus and assessed EIR in individual
      trigeminal ganglia. Compared to LAT(+) virus, LAT(-) virus reactivated poorly in
      Swiss Webster mice (P<0.05). In contrast, the EIR phenotype of these viruses was
      similar in BALB/c mice (P>0.1). Thus, LAT appeared to have a much greater impact
      on the EIR phenotype in Swiss Webster mice than in BALB/c mice. The mouse strain
      therefore appeared consequential in the HSV-1 EIR phenotype in mice.

PMID- 11297687
TI  - The genome of herpesvirus of turkeys: comparative analysis with Marek's disease
      viruses.
AB  - The complete coding sequence of the herpesvirus of turkeys (HVT) unique long
      (U(L)) region along with the internal repeat regions has been determined. This
      allows completion of the HVT nucleotide sequence by linkage to the sequence of
      the unique short (U(S)) region. The genome is approximately 160 kbp and shows
      extensive similarity in organization to the genomes of Marek's disease virus
      serotypes 1 and 2 (MDV-1, MDV-2) and other alphaherpesviruses. The HVT genome
      contains 75 ORFs, with three ORFs present in two copies. Sixty-seven ORFs were
      identified readily as homologues of other alphaherpesvirus genes. Seven of the
      remaining eight ORFs are homologous to genes in MDV, but are absent from other
      herpesviruses. These include a gene with similarity to cellular lipases. The
      final, HVT-unique gene is a virus homologue of the cellular NR-13 gene, the
      product of which belongs to the Bcl family of proteins that regulate apoptosis.
      No other herpesvirus sequenced to date contains a homologue of this gene. Of
      potential significance is the absence of a complete block of genes within the HVT
      internal repeat that is present in MDV-1. These include the pp38 and meq genes,
      which have been implicated in MDV-1-induced T-cell lymphoma. By implication,
      other genes present in this region of MDV-1, but missing in HVT, may play
      important roles in the different biological properties of the viruses.

PMID- 11297688
TI  - Binding of human and animal immunoglobulins to the IgG Fc receptor induced by
      human cytomegalovirus.
AB  - Human cytomegalovirus (HCMV)-infected cells express a virus-encoded receptor that
      is able to bind the Fc part of IGG: Some basic binding properties of this Fc
      receptor (FcR) have been examined. The affinity constant (K(a)) for human IgG Fc
      fragment in its interaction with acetone-fixed, HCMV-infected human embryonic
      lung fibroblasts was estimated to be around 2 x 10(8) M(-1) and the number of
      binding sites was estimated to be around 2 x 10(6) per cell. Of the human IgG,
      IgA, IgM and IgD classes, only IgG reacted with the receptor, and all four of the
      IgG subclasses were reactive. IgG from rabbit, hamster, cat, swine and horse
      exhibited binding to the HCMV FcR, in contrast to IgG from mouse, rat, guinea
      pig, dog, sheep, goat, cow and chicken. Immunoglobulins with and without HCMV IgG
      FcR-binding properties, like IgG from rabbit and mouse, can be of value in
      revealing the functional importance of the receptor. When the immunoglobulins
      were tested against herpes simplex virus type 1-induced FcR, both similarities
      and differences in immunoreactivity were seen relative to the HCMV FcR, which
      makes it unlikely that the binding sites for these two herpesvirus FcRs on the
      IgG molecule are identical.

PMID- 11297689
TI  - Late temporal gene expression from the human cytomegalovirus pp28US (UL99)
      promoter when integrated into the host cell chromosome.
AB  - Toward understanding the temporal regulation of human cytomegalovirus (HCMV) late
      genes, we studied the regulation of the late gene promoter (pp28US, UL99) when
      outside the context of the viral genome and its response to the immediate early
      (IE) proteins. Expression of the luciferase reporter gene, regulated by the
      pp28US promoter, was synchronous with that of the endogenous viral pp28 gene,
      independently of whether the reporter was episomal or integrated into the
      glioblastoma cell line U373MG. Cotransfection of the reporter with expression
      vectors for each of the three major IE genes, IE72, IE86 and IE55, indicated that
      only IE86 transactivated the pp28US promoter. However, the magnitude of the
      promoter activation upon HCMV infection suggested that additional factors are
      also required for higher promoter activity. The promoter activation was specific
      to HCMV, as herpes simplex virus type 1 infection did not induce luciferase
      expression.

PMID- 11297690
TI  - Epstein--Barr virus gene polymorphisms in Chinese Hodgkin's disease cases and
      healthy donors: identification of three distinct virus variants.
AB  - Epstein--Barr virus (EBV) is associated with several malignancies. Specific EBV
      gene variants, e.g. the BamHI f configuration, a C-terminal region 30 bp deletion
      in the latent membrane protein-1 (LMP1) gene (del-LMP) and the loss of an XhoI
      site in LMP1 (XhoI-loss), are found in Chinese cases of nasopharyngeal carcinoma
      (NPC), suggesting that EBV sequence variation may be involved in oncogenesis. In
      order to understand better the epidemiology of these EBV variants, they were
      studied in virus isolates from EBV-positive Chinese cases of Hodgkin's disease
      (HD; n=71) and donor throat washings from healthy CHINESE: Sequencing was
      performed of 15 representative EBV isolates, including the first analysis of the
      LMP1 promoter in Asian wild-type EBV isolates. The following observations were
      made. (i) Three EBV LMP1 variants were identified, designated Chinese groups (CG)
      1--3. In both EBV-associated HD and in healthy Chinese, CG1-like viruses showing
      del-LMP1 and XhoI-loss were predominant. (ii) CG1viruses were distinct from
      European and African variants, suggesting that this profile is useful for
      epidemiological studies. (iii) Specific patterns of mutations were present in the
      LMP1 promoter in both CG1 and CG2. (iv) The BamHI f variant was not found in
      Chinese HD, in contrast to Chinese NPC and European HD. This study confirms that
      EBV isolates in Chinese HD and other tumours differ from those reported in
      Western cases. However, this reflects the predominant virus strain present in the
      healthy Chinese population, suggesting that these are geographically restricted
      polymorphisms rather than tumour-specific strains.

PMID- 11297691
TI  - Demonstration by single-cell PCR that Reed--Sternberg cells and bystander B
      lymphocytes are infected by different Epstein--Barr virus strains in Hodgkin's
      disease.
AB  - Epstein--Barr virus (EBV) is associated with Hodgkin's disease (HD). However, EBV
      positive Reed--Sternberg (RS) cells and EBV-positive B lymphocytes co-exist in
      the same EBV-positive lymph node affected by HD. In a previous report, using
      total lymph node DNA, the presence of two distinct EBV strains was demonstrated,
      but their cellular localization (i.e. RS cells vs B lymphocytes) could not be
      determined. To address this question, three patients with EBV-associated HD were
      selected in the present study and single-cell PCR of the latent membrane protein
      1 (LMP-1) gene from isolated RS cells was performed. In one case, it was clear
      that RS cells and B lymphocytes were infected by different EBV strains. In the
      two remaining cases, only one band was detected from total lymph node DNA.
      However, single-cell PCR showed that RS cells in each sample were infected by
      single EBV strains, which were different from those detected in lymphoblastoid
      cell lines derived from EBV-positive B lymphocytes of lymph node cell suspensions
      from these two patients.

PMID- 11297692
TI  - Major histocompatibility complex class I molecules are down-regulated at the cell
      surface by the K5 protein encoded by Kaposi's sarcoma-associated
      herpesvirus/human herpesvirus-8.
AB  - The expression of major histocompatibility complex class I (MHC-I) molecules at
      the cell surface was down-regulated in BC-3 cells infected with Kaposi's sarcoma
      associated herpesvirus (KSHV)/human herpesvirus-8 at early times after treatment
      with 12-O-tetradecanoylphorbol acetate (TPA), and in HeLa cells transfected with
      the K5 gene of KSHV. However, an immunoprecipitation study on these cells with
      anti-MHC-I monoclonal antibody revealed that there was no significant reduction
      in the synthesis of MHC-I molecules. A pulse-chase analysis followed by
      endoglycosidase H digestion also demonstrated the stability and transport of MHC
      I molecules from the endoplasmic reticulum to at least the medial-GOLGI: K5
      antigen was clearly detected by immunohistological examination of samples from
      Kaposi's sarcoma, primary effusion lymphoma and Castleman's disease. These
      results suggest that the down-regulation of MHC-I molecules by K5 gene expression
      during reactivation may be important for evading immunological surveillance in
      the host.

PMID- 11297693
TI  - A bovine macrophage cell line supports bovine herpesvirus-4 persistent infection.
AB  - Although bovine herpesvirus-4 (BHV-4), a gammaherpesvirus lacking a clear disease
      association, has been demonstrated in many tissues during persistent BHV-4
      infection, a likely site of virus persistence is in cells of the
      monocyte/macrophage lineage. To establish an in vitro model of persistent
      infection potentially useful for examining the molecular mechanisms of BHV-4
      persistence/latency, we infected the bovine macrophage cell line BOMAC. Following
      extensive cell death, surviving cells were found to be persistently infected,
      maintaining the viral genome over many passages and producing low levels of
      infectious virus. Although selection was unnecessary for the maintenance of the
      viral genome, cells persistently infected with recombinant BHV-4 containing a
      neomycin-resistance gene could be selected with geneticin, thus confirming that
      persistent BHV-4 infection was compatible with cell survival and replication.
      Furthermore, persistent BHV-4 infection caused no decrease in the growth rate of
      BOMAC cells. Sodium butyrate, which reactivates latent gammaherpesviruses in
      vitro, or dexamethasone, which reactivates latent BHV-4 in vivo, increased viral
      DNA by 10- to 15-fold in persistently infected BOMAC cells. This suggests that
      reactivation of latent BHV-4 by dexamethasone in vivo might involve direct action
      of dexamethasone on latently infected cells.

PMID- 11297694
TI  - Characterization of the murine gammaherpesvirus 68 ORF74 product: a novel
      oncogenic G protein-coupled receptor.
AB  - Murine gammaherpesvirus (MHV-68) is well established as a small animal model for
      the study of gammaherpesviruses. The MHV-68 genome contains an open reading frame
      (ORF74) that has significant sequence homology with mammalian G-protein coupled
      receptors (GPCRs) and the GPCR from the related Kaposi's sarcoma-associated
      herpesvirus (KSHV). Here we show that the MHV-68 ORF74 is predicted to encode a
      GPCR since it has seven potential transmembrane helices and that it has other
      sequence motifs in common with GPCRS: Of interest is the observation that the
      sequence around a conserved arginine at the start of the second intracellular
      loop suggests that the ORF74 product may signal constitutively (agonist
      independent). Given that the ORF74 product is predicted to encode a GPCR we named
      it MHV-GPCR. In studies on the transcription of the MHV-GPCR, we determined that
      it was encoded on multiple early transcripts of 3.4, 4.4, 6.6 and 8.7 kb in size.
      At least one of these transcripts was bicistronic, containing the ORF encoding
      the Bcl-2 homologue also. In vivo, we found that MHV GPCR was expressed during
      acute infection but also during persistence, particularly in the lungs of
      infected mice. Immunofluorescence studies indicated that the MHV GPCR protein was
      expressed on the surface of cells in patches. Finally, like the KSHV GPCR,
      expression of the MHV GPCR resulted in transformation of NIH 3T3 cells. We
      surmise, therefore, that the MHV GPCR may act in concert with genes with which it
      is expressed such as vBcl-2 to enhance the growth and survival of MHV-68-infected
      cells.

PMID- 11297695
TI  - A mutational analysis of the vaccinia virus B5R protein.
AB  - A mutational analysis of the vaccinia virus (VV) B5R protein is presented. This
      protein is related to the regulators of complement activation (RCA) superfamily,
      has four short consensus repeats (SCRs) that are typical of this superfamily and
      is present on extracellular enveloped virus (EEV) particles. Here we have
      constructed VV mutants in which the cytoplasmic tail (CT) of the B5R protein is
      progressively truncated, and domains of the B5R protein [the SCR (short consensus
      repeat) domains, the transmembrane anchor region or the CT] are substituted by
      corresponding domains from the VV haemagglutinin (HA), another EEV protein.
      Analysis of these mutant viruses showed that loss of the B5R CT did not affect
      the formation of intracellular enveloped virus (IEV), actin tails, EEV or virus
      plaque size. However, if the SCR domains of the B5R protein were replaced by the
      corresponding region of the HA, the virus plaque size was diminished, the
      formation of actin tails was decreased severely and the titre of infectious EEV
      released from cells was reduced approximately 25-fold compared to wild-type virus
      and 5-fold compared to a virus lacking the entire B5R gene. Thus the linkage of
      HA to the B5R transmembrane and CT is deleterious for the formation and release
      of EEV and for cell-to-cell virus spread. In contrast, deletion or substitution
      of the B5R CT did not affect virus replication, although the amount of cell
      surface B5R was reduced compared to control.

PMID- 11297696
TI  - Genetic heterogeneity among parapoxviruses isolated from sheep, cattle and
      Japanese serows (Capricornis crispus).
AB  - Standard strains of four parapoxviruses and seven unclassified Japanese strains
      isolated from sheep, cattle and wild Japanese serows (Capricornis crispus) were
      compared molecularly. Restriction fragment length polymorphism (RFLP) analysis of
      viral DNA, indirect immunofluorescence assays using monoclonal antibodies,
      partial nucleotide sequencing of the envelope gene, phylogenetic analysis and PCR
      RFLP were carried out. These analyses revealed that the parapoxviruses were
      divided into four groups and the region sequenced in this study was highly
      conserved within each group. Each of the Japanese isolates was classified into
      one of these groups. These findings also indicated that parapoxvirus infections
      among wild Japanese serows seem to be caused by at least two different
      parapoxviruses, bovine papular stomatitis virus and orf virus. The methods
      presented here are useful for genetic characterization and classification of
      parapoxviruses.

PMID- 11297697
TI  - Genotypes of JC virus in East, Central and Southwest Europe.
AB  - Distinctive genotypes of JC virus have been described for the major continental
      landmasses. Studies on European-Americans and small cohorts in Europe showed
      predominantly Type 1. Types 2 and 7 are found in Asia, and Types 3 and 6 in
      Africa. These genotypes differ in sequence by about 1--3%. Each genotype may have
      several subtypes which differ from each other by about 0.5--1%. The genotypes can
      be defined by a distinctive pattern of nucleotides in a typing region of the VP1
      gene. This genotyping approach has been confirmed by phylogenetic reconstruction
      using the entire genome exclusive of the rearranging regulatory region. In this
      first large European study, we report on the urinary excretion of JCV DNA of 350
      individuals from Poland, Hungary, Germany and Spain. We included Gypsy cohorts in
      Hungary (Roma), Germany (Sinti), and Spain (Gitano), as well as Basques in Spain.
      We show that while Type 1 predominates in Europe, the proportions of Type 1A and
      1B may differ from East to Southwest Europe. Type 4, closely related to the Type
      1 sequence (only approximately 1% difference) was a minor genotype in Germany,
      Poland and Spain, but represented the majority in Basques. The Gitanos in Spain
      showed a variant Type 4 sequence termed 'Rom-1'. Interestingly, neither the
      Gitanos in Spain, nor Sinti or Roma in Germany or Hungary showed the Type 2 or
      Type 7 genotype that might be expected if their origins were in an Asian
      population.

PMID- 11297698
TI  - Identification of a genetic determinant of pathogenicity in chicken anaemia
      virus.
AB  - The molecular basis of pathogenicity of the chicken anaemia virus (CAV) needs to
      be clarified in order to develop a safe, live virus vaccine. In this study,
      several high- and low-pathogenic infectious DNA clones were obtained from field
      virus samples after 12 or 38 passages in MDCC-MSB1 cells. The high-pathogenic
      clones induced a low haematocrit, low weight gain and high mortality. Nucleotide
      sequence analyses identified one amino acid, at residue 394 of the VP1 capsid
      protein, as a major determinant of pathogenicity. To determine the role of this
      amino acid in pathogenicity, chimeric infectious DNA clones and point-mutated
      clones were used for chicken pathogenicity tests. These analyses clearly
      demonstrated that residue 394 of VP1 was crucial for the pathogenicity of CAV;
      all of the cloned viruses with glutamine at this position were highly pathogenic,
      whereas those with histidine had low pathogenicity. Low-pathogenic CAV, based on
      an infectious DNA clone, is a candidate for a genetically homogeneous and stable
      CAV live vaccine.

PMID- 11297699
TI  - Virus-specific spatial differences in the interference with silencing of the chs
      A gene in non-transgenic petunia.
AB  - Potyviruses, such as potato virus Y and tobacco etch virus, as well as cucumber
      mosaic cucumovirus, interfere with post-transcriptional gene silencing (PTGS).
      When RedStar-type Petunia hybrida cultivars, whose flowers have alternating white
      and pigmented sectors, were infected with these viruses, each virus induced a
      different pattern of restoration of floral anthocyanin pigmentation. Local
      reversion to coloured phenotypes in the white sectors, which occurred through
      interference with PTGS of the chalcone synthase A (chs-A) gene, was correlated
      with locally increased levels of chs-A mRNA and virus concentration. Our results
      show that virus infection can interfere with PTGS of a native plant gene, and
      that this can have profound effects on symptom expression.

PMID- 11297700
TI  - An Arabidopsis thaliana protein interacts with a movement protein of Turnip
      crinkle virus in yeast cells and in vitro.
AB  - Plant virus movement proteins bind host components to promote virus movement from
      initially infected cells to neighbouring cells. In this study, cDNA clones
      encoding p8 and p9, two small proteins required for the movement of Turnip
      crinkle virus, were used as 'bait' in a yeast two-hybrid system to screen an
      Arabidopsis thaliana cDNA library for interactive proteins. One A. thaliana clone
      was identified that encodes a protein, designated Atp8, which interacted with p8
      in yeast cells and in vitro. The apparent full-length of Atp8 mRNA was sequenced
      and shown to encode a protein with two possible transmembrane helices, several
      potential phosphorylation sites and two 'RGD' sequences.

PMID- 11297701
TI  - A reevaluation of the duration of survival after the onset of dementia.
AB  - BACKGROUND: Dementia shortens life expectancy; estimates of median survival after
      the onset of dementia have ranged from 5 to 9.3 years. Previous studies of people
      with existing dementia, however, may have underestimated the deleterious effects
      of dementia on survival by failing to consider persons with rapidly progressive
      illness who died before they could be included in a study (referred to as length
      bias). METHODS: We used data from the Canadian Study of Health and Aging to
      estimate survival from the onset of symptoms of dementia; the estimate was
      adjusted for length bias. A random sample of 10,263 subjects 65 years old or
      older from throughout Canada was screened for cognitive impairment. For those
      with dementia, we ascertained the date of onset and conducted follow-up for five
      years. RESULTS: We analyzed data on 821 subjects, of whom 396 had probable
      Alzheimer's disease, 252 had possible Alzheimer's disease, and 173 had vascular
      dementia. For the group as a whole, the unadjusted median survival was 6.6 years
      (95 percent confidence interval, 6.2 to 7.1). After adjustment for length bias,
      the estimated median survival was 3.3 years (95 percent confidence interval, 2.7
      to 4.0). The median survival was 3.1 years for subjects with probable Alzheimer's
      disease, 3.5 years for subjects with possible Alzheimer's disease, and 3.3 years
      for subjects with vascular dementia. CONCLUSIONS: Median survival after the onset
      of dementia is much shorter than has previously been estimated.

PMID- 11297702
TI  - Comparison of coronary-artery bypass surgery and stenting for the treatment of
      multivessel disease.
AB  - BACKGROUND: The recent recognition that coronary-artery stenting has improved the
      short- and long-term outcomes of patients treated with angioplasty has made it
      necessary to reevaluate the relative benefits of bypass surgery and percutaneous
      interventions in patients with multivessel disease. METHODS: A total of 1205
      patients were randomly assigned to undergo stent implantation or bypass surgery
      when a cardiac surgeon and an interventional cardiologist agreed that the same
      extent of revascularization could be achieved by either technique. The primary
      clinical end point was freedom from major adverse cardiac and cerebrovascular
      events at one year. The costs of hospital resources used were also determined.
      RESULTS: At one year, there was no significant difference between the two groups
      in terms of the rates of death, stroke, or myocardial infarction. Among patients
      who survived without a stroke or a myocardial infarction, 16.8 percent of those
      in the stenting group underwent a second revascularization, as compared with 3.5
      percent of those in the surgery group. The rate of event-free survival at one
      year was 73.8 percent among the patients who received stents and 87.8 percent
      among those who underwent bypass surgery (P<0.001 by the log-rank test). The
      costs for the initial procedure were $4,212 less for patients assigned to
      stenting than for those assigned to bypass surgery, but this difference was
      reduced during follow-up because of the increased need for repeated
      revascularization; after one year, the net difference in favor of stenting was
      estimated to be $2,973 per patient. CONCLUSION: As measured one year after the
      procedure, coronary stenting for multivessel disease is less expensive than
      bypass surgery and offers the same degree of protection against death, stroke,
      and myocardial infarction. However, stenting is associated with a greater need
      for repeated revascularization.

PMID- 11297703
TI  - Human papillomavirus infection as a risk factor for squamous-cell carcinoma of
      the head and neck.
AB  - BACKGROUND: Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV
      16), cause anogenital epithelial cancers and are suspected of causing epithelial
      cancers of the head and neck. METHODS: To examine the relation between head and
      neck cancers and HPVs, we performed a nested case-control study within a joint
      Nordic cohort in which serum samples were collected from almost 900,000 subjects.
      Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma
      of the head and neck developed, on average, 9.4 years after enrollment and from
      1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV
      33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase
      chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160
      of the study patients with cancer. RESULTS: After adjustment for cotinine levels,
      the odds ratio for squamous-cell carcinoma of the head and neck in subjects who
      were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to
      3.4). No increased risk was observed for other HPV types. Fifty percent of
      oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to
      PCR analysis. CONCLUSIONS: HPV-16 infection may be a risk factor for squamous
      cell carcinoma of the head and neck.

PMID- 11297704
TI  - The teratogenicity of anticonvulsant drugs.
AB  - BACKGROUND: The frequency of major malformations, growth retardation, and
      hypoplasia of the midface and fingers, known as the anticonvulsant embryopathy,
      is increased in infants exposed to anticonvulsant drugs in utero. However,
      whether the abnormalities are caused by the maternal epilepsy itself or by
      exposure to anticonvulsant drugs is not known. METHODS: We screened 128,049
      pregnant women at delivery to identify three groups of infants: those exposed to
      anticonvulsant drugs, those unexposed to anticonvulsant drugs but with a maternal
      history of seizures, and those unexposed to anticonvulsant drugs with no maternal
      history of seizures (control group). The infants were examined systematically for
      the presence of major malformations, signs of hypoplasia of the midface and
      fingers, microcephaly, and small body size. RESULTS: The combined frequency of
      anticonvulsant embryopathy was higher in 223 infants exposed to one
      anticonvulsant drug than in 508 control infants (20.6 percent vs. 8.5 percent;
      odds ratio, 2.8; 95 percent confidence interval, 1.1 to 9.7). The frequency was
      also higher in 93 infants exposed to two or more anticonvulsant drugs than in the
      controls (28.0 percent vs. 8.5 percent; odds ratio, 4.2; 95 percent confidence
      interval, 1.1 to 5.1). The 98 infants whose mothers had a history of epilepsy but
      took no anticonvulsant drugs during the pregnancy did not have a higher frequency
      of those abnormalities than the control infants. CONCLUSIONS: A distinctive
      pattern of physical abnormalities in infants of mothers with epilepsy is
      associated with the use of anticonvulsant drugs during pregnancy, rather than
      with epilepsy itself.

PMID- 11297705
TI  - Images in clinical medicine. Aneurysm of a saphenous-vein bypass graft.

PMID- 11297707
TI  - Epilepsy.

PMID- 11297706
TI  - Complement. Second of two parts.

PMID- 11297708
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 11-2001. Rapidly progressive renal failure in a 35-year-old woman
      with systemic lupus erythematosus.

PMID- 11297709
TI  - Aging and the public health effects of dementia.

PMID- 11297712
TI  - Absence of 5-HT(1B) receptors is associated with impaired impulse control in male
      5-HT(1B) knockout mice.
AB  - BACKGROUND: Serotonin (5-HT) plays a complex regulatory role in processes like
      anxiety, depression, aggression, and impulse control. Due to the large amount of
      serotonergic receptors, knockout mice offer an important opportunity to
      investigate the role of specific receptors. The 5-HT(1B) receptor is thought to
      mediate aggression and impulse control. This was studied here in mice lacking 5
      HT(1B) receptors (5-HT(1B) KO). METHODS: Wild type and 5-HT(1B) KO mice were
      exposed to several types of entrained and nonentrained stimuli. With telemetry,
      body temperature, heart rate, and locomotor activity were measured continuously
      during the different experiments. RESULTS: To nonentrained stimuli like
      disturbance stress and confrontation with an intruder, 5-HT(1B) KO mice showed
      exaggerated physiologic and behavioral responses. These mice displayed behavioral
      disinhibition, measured as increased social interest and aggression to an
      intruder mouse. However, in response to well-entrained stimuli like daily light
      transitions, responses were smaller in 5-HT(1B) KO than in wild type mice,
      suggesting that hyperreactivity is stimulus specific. CONCLUSIONS: Serotonin 1B
      receptors are essential in impulse control by inhibiting responses to
      nonentrained stimuli. Therefore, the 5-HT(1B) KO mouse might be an important
      additional model for studying aspects of disinhibition in aggression and impulse
      control.

PMID- 11297714
TI  - Genetic differences in the tail-suspension test and its relationship to
      imipramine response among 11 inbred strains of mice.
AB  - BACKGROUND: The tail suspension test (TST) is a simple screening test for the
      behavioral effects of antidepressants in rodents. This experiment investigated
      the interindividual differences in responses to stressful situations measured by
      duration of immobility in the TST and the effects of imipramine (30 mg/kg
      intraperitoneally) in reducing immobility among 11 inbred strains of mice. The 11
      inbred strains were 129S6/SvEvTac, A/J, AKR/J, Balb/cJ, C3H/HeJ, C57BL/6J,
      DBA/2J, FVB/NJ, NMRI, SencarA/PtJ, and SWR/J. METHODS: All mice underwent two
      trials of TST: 1) spontaneous, basal TST and 2) imipramine or saline TST. The
      duration of immobility was the trait measured during a 6-min test. RESULTS: In
      the four strains tested, female mice had longer duration of immobility than male
      mice in basal TST duration of immobility. For male mice (n = 11 strains),
      significant strain differences in immobility duration were found for both basal
      TST and imipramine response TST, with heritability estimates of .31 and .60,
      respectively. Immobility duration for the DBA/2J, FVB/NJ, and NMRI strains were
      significantly reduced by imipramine, relative to saline. Surprisingly, this
      reduction of immobility by imipramine was independent of the basal immobility.
      CONCLUSIONS: These results suggest that the responses on basal TST and the
      imipramine-mediated responses on TST are mediated by separate genetic pathways.

PMID- 11297713
TI  - Stress-induced hyperthermia in the 5-HT(1A) receptor knockout mouse is normal.
AB  - BACKGROUND: Several studies on serotonin 1A (5-HT(1A)) receptor knockout mice in
      different genetic backgrounds indicate that such mice display a more anxious
      phenotype than their corresponding wild types. We hypothesized that the 5-HT(1A)
      receptor knockout mice would show a different phenotype than the wild type mice
      in the stress-induced hyperthermia (SIH) paradigm, which tests putative
      anxiolytic effects of drugs. Moreover, on pharmacologic challenges with the 5
      HT(1A) receptor agonist flesinoxan we expected an absence of the functional
      response in knockout mice relative to wild type mice. METHODS: Effects of the 5
      HT(1A) receptor agonist flesinoxan, alone or in combination with the 5-HT(1A)
      receptor antagonist WAY-100635, and the gamma-aminobutyric acid A (GABA(A))
      benzodiazepine receptor agonist diazepam were studied in the SIH paradigm in male
      129/Sv 5-HT(1A) receptor knockout and wild type mice. In addition, the effects of
      flesinoxan on plasma corticosterone concentrations were determined. RESULTS:
      Plasma corticosterone concentrations were dose dependently elevated by flesinoxan
      in wild type mice but not in knockout mice. Flesinoxan dose dependently decreased
      SIH in wild type mice but not in knockout mice. The flesinoxan effect in wild
      type mice was blocked by WAY-100635. Furthermore, diazepam decreased SIH in both
      genotypes. There were no differences in basic SIH responses between wild type and
      knockout mice. CONCLUSIONS: 5 -HT(1A) receptor knockout mice display a normal SIH
      response, and results indicate, based on the SIH, that the GABA(A)-benzodiazepine
      receptor complex functions normally.

PMID- 11297715
TI  - Aberrant respiratory sensitivity to CO(2) as a trait of familial panic disorder.
AB  - BACKGROUND: According to three earlier studies, well individuals with a family
      history of panic disorder experience more anxiety following a single breath of
      35% CO(2) than do those without such a family history. This study sought to
      determine whether a heightened sensitivity to CO(2) manifests specifically in
      respiratory changes. METHODS: Subjects were 18--35 years old and had no history
      of panic attacks and no current DSM-IV diagnosis other than simple or social
      phobia. Those at high risk for panic disorder (HR-P) (n = 46) had a first-degree
      relative with treated panic disorder. Low-risk control subjects (LR-C) (n = 39)
      had no first-degree relative with panic disorder. Respiratory measurements were
      taken continuously while subjects breathed room air through an attached mask for
      3 min and, subsequently, while they breathed a 5% CO(2)/air mixture for an
      additional 3 min. RESULTS: HR-P subjects did not differ from control subjects by
      group means of the principal measure of respiratory response, changes in minute
      volume (MV) during CO(2) inhalation. However, these values assumed clearly
      different distributions in the two groups. Fifteen (32.6%) of the HR-P subjects
      showed a paradoxical decrease in MV while breathing CO(2) and six (13%) displayed
      a particularly rapid increase in MV. Only one (2.6%) of the control subjects had
      a negative MV slope and none had a high value [chi(2)(1) = 12.3, p <.001, p
      =.021, Fisher exact test, respectively]. Though the subjects with high MV
      increases also described greater increases in anxiety after breathing CO(2), a
      regression analysis indicated that the MV increase was the more important in
      discriminating high-risk from control subjects. CONCLUSIONS: These results
      suggest that respiratory sensitivity to CO(2) inhalation is operative in the
      familial transmission of panic disorder.

PMID- 11297716
TI  - Persistent respiratory irregularity in patients with panic disorder.
AB  - BACKGROUND: Dysregulated respiratory control may play a role in the
      pathophysiology of panic disorder. This could be due to abnormalities in brain
      stem respiratory nuclei or to dysregulation at higher brain levels. Results from
      previous studies using the doxapram model of panic have yielded an unclear
      picture. A brief cognitive manipulation reduced doxapram-induced hyperventilation
      in patients, suggesting that higher level inputs can substantially alter their
      respiratory patterns. However, respiratory abnormalities persisted, including a
      striking irregularity in breathing patterns. METHODS: To directly study
      respiratory irregularity, breath-by-breath records of tidal volume (V(t)) and
      frequency (f) from previously studied subjects were obtained. Irregularity was
      quantified using von Neumann's statistic and calculation of "sigh" frequency in
      16 patients and 16 matched control subjects. Half of each group received a
      standard introduction to the study and half received a cognitive intervention
      designed to reduce anxiety/distress responses to the doxapram injection. RESULTS:
      Patients had significantly greater V(t) irregularity relative to control
      subjects. Neither the cognitive intervention nor doxapram-induced
      hyperventilation produced significant changes in V(t) irregularity. The V(t)
      irregularity was attributable to a sighing pattern of breathing that was
      characteristic of panic patients but not control subjects. Patients also had
      somewhat elevated f irregularity relative to control subjects. CONCLUSIONS: The
      irregular breathing patterns in panic patients appear to be intrinsic and stable,
      uninfluenced by induced hyperventilation or cognitive manipulation. Further study
      of V(t) irregularity and sighs are warranted in efforts to localize dysregulated
      neural circuits in panic to brain stem or midbrain levels.

PMID- 11297717
TI  - Physiologic instability in panic disorder and generalized anxiety disorder.
AB  - BACKGROUND: Because panic attacks can be accompanied by surges in physiologic
      activation, we tested the hypothesis that panic disorder is characterized by
      fluctuations of physiologic variables in the absence of external triggers.
      METHODS: Sixteen patients with panic disorder, 15 with generalized anxiety
      disorder, and 19 normal control subjects were asked to sit quietly for 30 min.
      Electrodermal, cardiovascular, and respiratory measures were analyzed using
      complex demodulation to quantify variability in physiologic indices. RESULTS:
      Both patient groups reported equally more anxiety and cardiac symptoms than
      control subjects, but certain other somatic symptoms, including breathlessness,
      were elevated only in panic disorder patients. Mean end-tidal pCO(2) and
      respiratory rates were lower, and tidal volume and the number of sighs were
      higher in panic disorder patients than control subjects. Neither cardiovascular
      (heart rate, arterial pressure, cardiac output), nor electrodermal instability
      including sighs distinguished the groups; however, tidal volume instability was
      greater in panic disorder than generalized anxiety disorder patients or control
      subjects. Several other respiratory measures (pCO(2), respiratory rate, minute
      volume, duty cycle) showed greater instability in both patient groups than in
      control subjects. CONCLUSIONS: Respiration is particularly unstable in panic
      disorder, underlining the importance of respiratory physiology in understanding
      this disorder. Whether our findings represent state or trait characteristics is
      discussed.

PMID- 11297718
TI  - Characteristics of sighing in panic disorder.
AB  - BACKGROUND: Sighs, breaths with larger tidal volumes than surrounding breaths,
      have been reported as being more frequent in patients with anxiety disorders.
      METHODS: Sixteen patients with panic disorder, 15 with generalized anxiety
      disorder, and 19 normal control subjects were asked to sit quietly for 30 min.
      Respiratory volumes and timing were recorded with inductive plethysmography and
      expired pCO(2), from nasal prongs. RESULTS: Panic disorder patients sighed more
      and had tonically lower end-tidal pCO(2)s than control subjects, whereas
      generalized anxiety disorder patients were intermediate. Sighs defined as >2.0
      times the subject mean discriminated groups best. Sigh frequency was more
      predictive of individual pCO(2) levels than was minute volume. Ensemble averaging
      of respiratory variables for sequences of breaths surrounding sighs showed no
      evidence that sighs were triggered by increased pCO(2) or reduced tidal volume in
      any group. Sigh breaths were larger in panic disorder patients than in control
      subjects. After sighs, pCO(2) and tidal volume did not return to baseline levels
      as quickly in panic disorder patients as in control subjects. CONCLUSIONS:
      Hypocapnia in panic disorder patients is related to sigh frequency. In none of
      the groups was sighing a homeostatic response. Panic disorder patients show less
      peripheral chemoreflex gain than control subjects, which would maintain low
      pCO(2) levels after sighing.

PMID- 11297719
TI  - Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation
      (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory
      threshold in depressed patients.
AB  - BACKGROUND: The safety of repetitive transcranial magnetic stimulation (rTMS) has
      only previously been formally studied in volunteers receiving a single session of
      stimulation or in a small number of depressed subjects receiving a 2-week
      treatment course. This study examined safety issues in depressed subjects
      receiving up to 4 weeks of rTMS. Efficacy results from this study have been
      previously reported. METHODS: Eighteen subjects with DSM-IV major depression
      participated in a 2-week, parallel, double-blind, sham-controlled study of rTMS
      treatment. Twelve subjects then went on to receive 4 weeks active rTMS in an open
      follow-up. We examined the effects of rTMS on neuropsychologic function (up to 4
      weeks), auditory threshold (up to 6 weeks exposure to rTMS noise), and an
      electroencephalogram (after 2 weeks). Data were analyzed by repeated measures
      analysis. RESULTS: There were trends for improvement in neuropsychologic
      performance, probably due to practice effects. No mean changes in auditory
      threshold occurred, but two patients showed mild high-frequency hearing loss
      after several weeks of rTMS. Electroencephalograms in two patients, one of whom
      had sham stimulation, showed minor abnormality. CONCLUSIONS: No significant mean
      deficits were demonstrated in this cohort. Overall, rTMS for up to 4 weeks is
      safe, but individual results suggest caution and the need for further
      investigation of the safety of several weeks of rTMS.

PMID- 11297720
TI  - Pupillary and reaction time measures of sustained processing of negative
      information in depression.
AB  - BACKGROUND: Disruptions of emotional information processing (i.e., attention to,
      memory for, and interpretation of emotional information) have been implicated in
      the onset and maintenance of depression. The research presented here investigated
      cognitive and psychophysiological features of a particularly promising correlate
      of depression: sustained processing of negative information 4--5 sec after an
      emotional stimulus. METHODS: Pupil dilation data and reaction times were
      collected from 24 unmedicated depressed and 25 nondepressed adults in response to
      emotional processing tasks (lexical decision and valence identification) that
      employed idiosyncratically generated personally relevant and normed stimuli.
      Pupil dilation was used to index sustained cognitive processing devoted to
      stimuli. RESULTS: Consistent with predictions, depressed individuals were
      especially slow to name the emotionality of positive information, and displayed
      greater sustained processing (pupil dilation) than nondepressed individuals when
      their attention was directed toward emotional aspects of information. Contrary to
      predictions, depressed participants did not dilate more to negative than positive
      stimuli, compared to nondepressed participants. CONCLUSIONS: These data suggest
      depressed individuals may not initially attend to emotional aspects of
      information but may continue to process them seconds after they have reacted to
      the information.

PMID- 11297721
TI  - Vagal modulation of responses to mental challenge in posttraumatic stress
      disorder.
AB  - BACKGROUND: Studies of the autonomic nervous system in posttraumatic stress
      syndrome (PTSD) have focused on the sympathetic modulation of arousal and have
      neglected the parasympathetic contribution. This study addresses the
      parasympathetic control of heart rate in individuals who have survived traumatic
      events. METHODS: Twenty-nine survivors, 14 with current PTSD and 15 without,
      participated in the study. The groups were comparable with regard to age, type of
      trauma, time since the latest traumatic event, and lifetime exposure to traumatic
      events. Electrocardiograms were recorded during rest and an arithmetic task.
      Heart period, respiratory sinus arrhythmia (RSA), and the amplitude of the Traube
      Hering-Mayer wave were quantified. RESULTS: The groups did not differ on resting
      measures. During the arithmetic task, the past trauma group showed a significant
      increase in RSA (p <.007), whereas the PTSD group did not. In the past trauma
      group only, RSA and heart period were highly correlated (r =.75), thereby
      suggesting that the response to challenge was under vagal control. CONCLUSIONS:
      Trauma survivors who develop PTSD differ from those who do not in the extent to
      which their heart rate response to challenge is controlled by vagal activity.
      Responses to challenge in PTSD may be mediated by nonvagal, possibly sympathetic
      mechanisms.

PMID- 11297722
TI  - Double-blind placebo-controlled administration of fluoxetine in restricting- and
      restricting-purging-type anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa is an often chronic disorder with high morbidity and
      mortality. Many people relapse after weight restoration. This study was designed
      to determine whether a selective serotonin reuptake inhibitor would improve
      outcome and reduce relapse after weight restoration by contributing to
      maintenance of a healthy normal weight and a reduction of symptoms. METHODS: We
      administered a double-blind placebo-controlled trial of fluoxetine to 35 patients
      with restricting-type anorexia nervosa. Anorexics were randomly assigned to
      fluoxetine (n = 16) or a placebo (n = 19) after inpatient weight gain and then
      were observed as outpatients for 1 year. RESULTS: Ten of 16 (63%) subjects
      remained on fluoxetine for a year, whereas only three of 19 (16%) remained on the
      placebo for a year (p =.006). Those subjects remaining on fluoxetine for a year
      had reduced relapse as determined by a significant increase in weight and
      reduction in symptoms. CONCLUSIONS: This study offers preliminary evidence that
      fluoxetine may be useful in improving outcome and preventing relapse of patients
      with anorexia nervosa after weight restoration.

PMID- 11297723
TI  - The rotor in the membrane of the ATP synthase and relatives.
AB  - In recent years, structural information on the F(1) sector of the ATP synthase
      has provided an insight into the molecular mechanism of ATP catalysis. The
      structure strongly supports the proposal that the ATP synthase works as a rotary
      molecular motor. Insights into the membrane domain have just started to emerge
      but more detailed structural information is needed if the molecular mechanism of
      proton translocation coupled to ATP synthesis is to be understood. This review
      will focus mainly on the ion translocating rotor in the membrane domain of the F
      type ATPase, and the related vacuolar and archaeal relatives.

PMID- 11297724
TI  - A putative proton binding site of plasma membrane H(+)-ATPase identified through
      homology modelling.
AB  - We have used the 2.6 A structure of the rabbit sarcoplasmic reticulum Ca(2+)
      ATPase isoform 1a, SERCA1a [Toyoshima, C., Nakasako, M., Nomura, H. and Ogawa, H.
      (2000) Nature 405, 647-655], to build models by homology modelling of two plasma
      membrane (PM) H(+)-ATPases, Arabidopsis thaliana AHA2 and Saccharomyces
      cerevisiae PMA1. We propose that in both yeast and plant PM H(+)-ATPases a
      strictly conserved aspartate in transmembrane segment (M)6
      (D684(AHA2)/D730(PMA1)), and three backbone carbonyls in M4
      (I282(AHA2)/I331(PMA1), G283(AHA2)/I332(PMA1) and I285(AHA2)/V334(PMA1)) comprise
      a binding site for H3O(+), suggesting a previously unknown mechanism for
      transport of protons. Comparison with the structure of the SERCA1a made it
      feasible to suggest a possible receptor region for the C-terminal auto-inhibitory
      domain extending from the phosphorylation and anchor domains into the
      transmembrane region.

PMID- 11297725
TI  - The structure and nucleotide occupancy of bovine mitochondrial F(1)-ATPase are
      not influenced by crystallisation at high concentrations of nucleotide.
AB  - Analysis of tryptophan mutants of F(1)-ATPase from Escherichia coli [Lobau et al.
      (1997) FEBS Lett. 404, 15-18] suggested that nucleotide concentrations used to
      grow crystals for the determination of the structure of bovine F(1)-ATPase
      [Abrahams et al. (1994) Nature 370, 621-628] would be sufficient to occupy only
      two catalytic sites, and that higher concentrations of nucleotide would result in
      all three sites being occupied. We have determined the structure of bovine F(1)
      ATPase at 2.9 A resolution with crystals grown in the presence of 5 mM AMPPNP and
      5 microM ADP. Similar to previous structures of bovine F(1)-ATPase determined
      with crystals grown in the presence of lower nucleotide concentrations, only two
      beta-subunits have bound nucleotide and the third subunit remains empty.

PMID- 11297726
TI  - Antibodies to the CFTR modulate the turgor pressure of guard cell protoplasts via
      slow anion channels.
AB  - The plasma membrane guard cell slow anion channel is a key element at the basis
      of water loss control in plants allowing prolonged osmolite efflux necessary for
      stomatal closure. This channel has been extensively studied by
      electrophysiological approaches but its molecular identification is still
      lacking. Recently, we described that this channel was sharing some similarities
      with the mammalian ATP-binding cassette protein, cystic fibrosis transmembrane
      conductance regulator (CFTR) chloride channel [Leonhardt, N. et al. (1999) Plant
      Cell 11, 1141-1151]. Here, using the patch-clamp technique and a bioassay,
      consisting in the observation of the change in guard cell protoplasts volume, we
      demonstrated that a functional antibody raised against the mammalian CFTR
      prevented ABA-induced guard cell protoplasts shrinking and partially inhibited
      the slow anion current. Moreover, this antibody immunoprecipitated a polypeptide
      from guard cell protein extracts and immunolabeled stomata in Vicia faba leaf
      sections. These results indicate that the guard cell slow anion channel is, or is
      closely controlled by a polypeptide, exhibiting one epitope shared with the
      mammalian CFTR.

PMID- 11297727
TI  - Contribution of the DDDD motif of H. influenzae e (P4) to phosphomonoesterase
      activity and heme transport.
AB  - Haemophilus influenzae lipoprotein e (P4) is a member of the DDDD
      phosphohydrolase superfamily and mediates heme transport. Each of the aspartate
      residues of the signature motif is required for phosphomonoesterase activity, as
      none of the e (P4) single D mutants (D64A, D66A, D181N, and D185A) possessed
      detectable phosphomonoesterase activity. These results suggest that the signature
      motif is essential to the phosphomonoesterase activity of lipoprotein e (P4).
      When assessed for phosphomonoesterase-dependent heme transport activity in
      Escherichia coli hemA strains, plasmids containing D181N and D185A retained heme
      transport as indicated by aerobic growth while D64A and D66A did not. We conclude
      that phosphomonoesterase activity is not required for heme transport.

PMID- 11297728
TI  - Light activates a 46-kDa MAP kinase-like protein kinase in soybean cell culture.
AB  - Light induced rapid and transient activation of a 46-kDa protein kinase in
      soybean photomixotrophic cell culture. This kinase was designated as LAP kinase
      (light signal-activated protein kinase). Activation of LAP kinase in response to
      light was associated with tyrosine phosphorylation of the kinase, and treatment
      of the kinase with protein tyrosine phosphatase abolished its activity. The LAP
      kinase efficiently phosphorylated myelin basic protein and histone, but did not
      phosphorylate casein. Phospho-amino acid analysis indicated that the LAP kinase
      was a serine/threonine protein kinase. These results indicated that the LAP
      kinase is related to the MAP kinase family of protein kinases.

PMID- 11297729
TI  - Intrinsic fluorescence changes and rapid kinetics of proteinase deformation
      during serpin inhibition.
AB  - The X-ray crystal structure of the serpin-proteinase complex suggested that the
      serpin deformed the proteinase thereby inactivating the molecule. Using a variant
      of alpha(1)-antitrypsin in which both tryptophan residues have been replaced by
      phenylalanine, we have shown that the proteinase becomes partially unfolded
      during serpin inhibition. The tryptophan free variant, alpha(1)
      antitrypsin((FF)), is fully active as an inhibitor of thrombin. Thrombin has a
      fluorescence emission maximum of 340 nm which blue shifts to 346 nm, concomitant
      with a 40% increase in intensity, upon formation of the serpin-proteinase complex
      indicative of substantial conformational change within the proteinase. Stopped
      flow analysis of the fluorescence changes within the proteinase indicated a two
      step mechanism. A fast bimolecular reaction with a rate constant of 2.8x10(6) M(
      1) s(-1) is followed by a slow unimolecular process with a rate of 0.26 s(-1)
      that is independent of concentration. We propose that the first rate is formation
      of an initial complex which is then followed by a slower process involving the
      partial unfolding of the proteinase during its translocation to the opposite pole
      of the serpin.

PMID- 11297730
TI  - Substitution of a conserved aspartate allows cation-induced polymerization of
      FtsZ.
AB  - The prokaryotic tubulin homologue FtsZ polymerizes in vitro in a nucleotide
      dependent fashion. Here we report that replacement of the strictly conserved
      Asp212 residue of Escherichia coli FtsZ by a Cys or Asn, but not by a Glu residue
      results in FtsZ that polymerizes with divalent cations in the absence of added
      GTP. FtsZ D212C and D212N mutants co-purify with GTP as bound nucleotide,
      providing an explanation for the unusual phenotype. We conclude that D212 plays a
      critical role in the coordination of a metal ion and the nucleotide at the
      interface of two FtsZ monomers.

PMID- 11297731
TI  - The second cysteine-rich domain of Mac1p is a potent transactivator that
      modulates DNA binding efficiency and functionality of the protein.
AB  - Mac1p is a Saccharomyces cerevisiae DNA binding transcription factor that
      activates genes involved in copper uptake. A copper-induced N-C-terminal
      intramolecular interaction and copper-independent homodimerization affect its
      function. Here, we present a functional analysis of Mac1p deletion derivatives
      that attributes new roles to the second cysteine-rich (REPII) domain of the
      protein. This domain exhibits the copper-responsive potent transactivation
      function when assayed independently and, in the context of the entire protein,
      modulates the efficiency of Mac1p binding to DNA. The efficiency of binding to
      both copper-response promoter elements can determine the in vivo functionality of
      Mac1p independent of homodimerization.

PMID- 11297732
TI  - Immunocytological localization of two plant fatty acid desaturases in the
      endoplasmic reticulum.
AB  - The subcellular location of two integral membrane-bound fatty acid desaturases
      (Fads), Fad2 and Fad3, was elucidated by immunofluorescence microscopic analyses
      of tobacco suspension cells transiently transformed with different epitope-tagged
      versions of the enzymes. Both myc- or hemagglutinin-tagged Fad2 and Fad3
      localized to the same region of the endoplasmic reticulum (ER), as evidenced by
      their co-localization with the ER lumenal protein calreticulin. Results from
      differential permeabilization experiments revealed that the N-termini of both
      epitope-tagged Fad2 and Fad3 were exposed on the cytosolic side of ER membranes.
      These data define the subcellular location and topological orientation of plant
      desaturases in ER membranes.

PMID- 11297733
TI  - Phosphorylation of neurofibromin by cAMP-dependent protein kinase is regulated
      via a cellular association of N(G),N(G)-dimethylarginine dimethylaminohydrolase.
AB  - The neurofibromatosis type 1 (NF1) tumor suppressor (neurofibromin) is thought to
      play crucial roles in cellular Ras- and cAMP-dependent kinase (PKA)-associated
      signals. In this study, we identified a cellular neurofibromin-associating
      protein, N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH) that is known
      as a cellular NO/NOS regulator. The interaction of DDAH was mainly directed to
      the C-terminal domain (CTD) and to the cysteine/serine-rich domain (CSRD) of
      neurofibromin, coinciding with the regions containing specific PKA
      phosphorylation sites. DDAH increased PKA phosphorylation of native neurofibromin
      in a dose-dependent manner, especially affecting the phosphorylation of CSRD.
      These findings suggest that the PKA accessibility of neurofibromin was regulated
      via DDAH interaction, and this regulation may modulate the cellular function of
      neurofibromin that is implicated in NF1-related pathogenesis.

PMID- 11297734
TI  - DFNA5 (ICERE-1) contributes to acquired etoposide resistance in melanoma cells.
AB  - Resistance to drug treatment is a common observation in malignant melanoma. In
      order to analyze alterations in mRNA expression profiles associated with drug
      resistance in melanoma cells we previously established a panel of various drug
      resistant cell variants derived from the human melanoma line MeWo and compared
      the mRNA expression profiles by a differential display technique. By that
      approach it could be demonstrated that the expression level of a mRNA encoded by
      a gene found to be mutated in non-syndromic hearing impairment, DFNA5 (ICERE-1),
      was distinctly decreased in the 33-fold etoposide-resistant melanoma cell line
      MeWo ETO 1. To evaluate the hypothesis that a decrease in DFNA5 mRNA expression
      level contributes to the acquired etoposide resistance phenotype exhibited by
      MeWo ETO 1 cells, this drug-resistant line was stably transfected with the DFNA5
      encoding cDNA. Transfected clones showed a 30-35% reduced etoposide
      susceptibility by comparing the IC(25), IC(50) and IC(75) values of these clones
      with those displayed by the non-transfected, etoposide-resistant melanoma cell
      line MeWo ETO 1 and controls. Furthermore, etoposide exposure of stable DFNA5
      transfectants resulted in an increase of caspase-3-mediated apoptotic events in
      DFNA5-transfected clones in comparison to MeWo ETO 1 cells and controls. The data
      therefore demonstrate that a decrease in DNFA5 mRNA expression level is
      associated with an increased etoposide resistance in melanoma cells due to an
      elevated cellular susceptibility to trigger a caspase-3-depending signal pathway
      leading to programmed cell death.

PMID- 11297735
TI  - PKC phosphorylation of a conserved serine residue in the C-terminus of group III
      metabotropic glutamate receptors inhibits calmodulin binding.
AB  - Group III metabotropic glutamate receptors (mGluRs) serve as presynaptic
      receptors that mediate feedback inhibition of glutamate release via a
      Ca(2+)/calmodulin (CaM)-dependent mechanism. In vitro phosphorylation of mGluR7A
      by protein kinase C (PKC) prevents its interaction with Ca(2+)/CaM. In addition,
      activation of PKC leads to an inhibition of mGluR signaling. Here, we demonstrate
      that disrupting CaM binding to mGluR7A by PKC in vitro is due to phosphorylation
      of a highly conserved serine residue, S862. We propose charge neutralization of
      the CaM binding consensus sequence resulting from phosphorylation to constitute a
      general mechanism for the regulation of presynaptic mGluR signaling.

PMID- 11297736
TI  - Why Ppr1p is a weak activator of transcription.
AB  - Upon uracil depletion, the transcriptional activator Ppr1p stimulates expression
      of the Saccharomyces cerevisiae URA3 gene only four-fold. We performed a split
      ubiquitin screen with Tup1p as bait, and we found that the global repressor Tup1p
      interacts with the transcriptional activator Ppr1p both in vivo and in vitro. The
      interaction is biologically significant, since the deletion of the TUP1 gene as
      well as the removal of the Tup1p-binding domain from Ppr1p results in an
      increased expression of the URA3 gene. Our results suggest that Tup1p blocks
      Ppr1p directly, and that Ppr1p is a weak activator of transcription because of
      its interaction with Tup1p. Thus we were able to demonstrate that the global
      repressor Tup1p can modulate transcription by interacting with an activator.

PMID- 11297737
TI  - The speckling domain of the Wilms tumor suppressor WT1 overlaps with the
      transcriptional repression domain.
AB  - The Wilms tumor suppressor gene WT1 encodes a zinc finger protein, expressed as
      different splicing variants, that has all the hallmarks of a transcription
      factor. The -KTS form of WT1 displays a homogeneous localization within the
      nucleus and has been shown to activate or repress the activity of various target
      genes. In contrast, the WT1(+KTS) variant demonstrates a speckled pattern of
      expression within the nucleus. This and its association with factors of the
      splicing machinery has led to the hypothesis that WT1(+KTS) might play a role in
      post-transcriptional processes. By the generation of a series of deletion
      constructs and subsequent immunofluorescence analysis, we have identified and
      characterized the domain which is responsible for the localization of WT1
      variants in nuclear speckles. The speckling domain comprises amino acids 76-120
      within the N-terminus of WT1 and is sufficient to target other proteins into
      distinct nuclear domains. Interestingly the WT1 speckling domain does not overlap
      with the domain required for interaction with the splicing factor U2AF65 but
      overlaps with the transcriptional repression domain. Thus our data challenge the
      view that association of WT1 with spliceosomes is responsible for the speckling
      phenotype.

PMID- 11297738
TI  - Trp122 and Trp134 on the surface of the catalytic domain are essential for
      crystalline chitin hydrolysis by Bacillus circulans chitinase A1.
AB  - From the 3D-structural analysis of the catalytic domain of chitinase A1, two
      exposed tryptophan residues (W122 and W134) are proposed to play an important
      role in guiding a chitin chain into the catalytic cleft during the crystalline
      chitin hydrolysis. Mutation of either W122 or W134 to alanine significantly
      reduced the hydrolyzing activity against highly crystalline beta-chitin
      microfibrils. Double mutation almost completely abolished the hydrolyzing
      activity. On the other hand, the hydrolyzing activity against either soluble or
      amorphous substrate was not reduced. These mutations slightly impaired the
      binding activity of this enzyme. These results clearly demonstrated that the two
      exposed aromatic residues play a critical role in hydrolyzing the chitin chain in
      crystalline chitin.

PMID- 11297739
TI  - Characterization of a novel human putative mitochondrial transporter homologous
      to the yeast mitochondrial RNA splicing proteins 3 and 4.
AB  - We report here a novel human gene, hMRS3/4, encoding a putative mitochondrial
      transporter structurally and functionally homologous to the yeast mitochondrial
      RNA splicing proteins 3 and 4. These proteins belong to the family of
      mitochondrial carrier proteins (MCF) and are likely to function as solute
      carriers. hMRS3/4 spans approximately 10 kb of genomic DNA on chromosome 10q24
      and consists of four exons that encode a 364-aa protein with six transmembrane
      domains. A putative splice variant, encoding a 177-aa protein with three
      transmembrane domains, was also identified. hMRS3/4 has a well-conserved
      signature sequence of MCF and is targeted into the mitochondria. When expressed
      in yeast, hMRS3/4 efficiently restores the mitochondrial functions in
      mrs3(o)mrs4(o) knock-out mutants. Ubiquitous expression in human tissues and a
      well-conserved structure and function suggest an important role for hMRS3/4 in
      human cells.

PMID- 11297740
TI  - A novel heterodimeric antimicrobial peptide from the tree-frog Phyllomedusa
      distincta.
AB  - We present here the purification and the analysis of the structural and
      functional properties of distinctin, a 5.4 kDa heterodimeric peptide with
      antimicrobial activity from the tree-frog Phyllomedusa distincta. This peptide
      was isolated from the crude extract of skin granular glands by different
      chromatographic steps. Its minimal inhibitory concentration was determined
      against pathogenic Escherichia coli, Staphylococcus aureus, Enterococcus faecalis
      and Pseudomonas aeruginosa strains. Amino acid sequencing and mass spectrometric
      investigations demonstrated that distinctin is constituted of two different
      polypeptide chains connected by an intermolecular disulphide bridge. Circular
      dichroism and Fourier-transformed infrared spectroscopy studies showed that this
      molecule adopts, in water, a structure containing a significant percentage of
      anti-parallel beta-sheet. A conformational variation was observed under
      experimental conditions mimicking a membrane-like environment. Database searches
      did not show sequence similarities with any known antimicrobial peptides. In the
      light of these results, we can consider distinctin as the first example of a new
      class of antimicrobial heterodimeric peptides from frog skin.

PMID- 11297741
TI  - Functional characterization of sphingolipid C4-hydroxylase genes from Arabidopsis
      thaliana.
AB  - In the genome of Arabidopsis thaliana, two genes were identified encoding
      isoenzymes for C4-hydroxylation of long chain bases (LCB) in plant sphingolipids.
      Both predicted proteins consist of 258 amino acid residues (77% identity) which
      show sequence similarity to di-iron-binding enzymes, such as Sur2p and Erg3p from
      yeast, involved in oxygen-dependent lipid modifications. Heterologous expression
      of these genes in a yeast sur2Delta-null mutant lacking C4-LCB hydroxylation
      resulted in the formation of D-ribo-C(18)- and -C(20)-phytosphinganine. The
      identity and stereochemical configuration of the isolated trihydroxybases was
      confirmed by electrospray ionization-mass spectroscopy, gas-liquid chromatography
      mass spectrometry and 1H-nuclear magnetic resonance spectroscopy. These results
      represent the first functional identification of SUR2 genes from plants as well
      as from any organism other than yeast.

PMID- 11297742
TI  - Re-face stereospecificity of NADP dependent methylenetetrahydromethanopterin
      dehydrogenase from Methylobacterium extorquens AM1 as determined by NMR
      spectroscopy.
AB  - MtdA catalyzes the dehydrogenation of N(5),N(10)-methylenetetrahydromethanopterin
      (methylene-H4MPT) with NADP(+) as electron acceptor. In the reaction two
      prochiral centers are involved, C14a of methylene-H4MPT and C4 of NADP(+),
      between which a hydride is transferred. The two diastereotopic protons at C14a of
      methylene-H4MPT and at C4 of NADPH can be seen separately in 1H-NMR spectra. This
      fact was used to determine the stereospecificity of the enzyme. With (14aR)-[14a
      2H(1)]-[14a-13C]methylene-H4MPT as the substrate, it was found that the pro-R
      hydrogen of methylene-H4MPT is transferred by MtdA into the pro-R position of
      NADPH.

PMID- 11297743
TI  - A small upstream open reading frame causes inhibition of human major vault
      protein expression from a ubiquitous mRNA splice variant.
AB  - Overexpression of the major vault protein (MVP) has been linked to a multidrug
      resistance (MDR) phenotype. We describe a ubiquitously expressed MVP mRNA splice
      variant (long (L)-MVP) differing from the regular isoform (short (S)-MVP) within
      the 5'-leader. Only L-MVP mRNA contains a small upstream open reading frame which
      was proven to inhibit in vitro and in vivo MVP expression in cis. L-MVP
      represented an almost constant portion of total MVP mRNA in diverse normal
      tissues, but was more variable in malignant cell types. MDR sublines with altered
      MVP expression displayed changed S-MVP/L-MVP ratios as compared to their drug
      sensitive counterparts. Our results suggest alternative splicing as one mechanism
      for regulation of MVP expression.

PMID- 11297745
TI  - Non-destructive quantitation of spermine in human prostate tissue samples using
      HRMAS 1H NMR spectroscopy at 9.4 T.
AB  - We present the results of a study of human prostate specimens evaluated by high
      resolution magic angle spinning (1)H nuclear magnetic resonance (NMR)
      spectroscopy at 400 MHz (9.4 T) and by quantitative histopathology. We
      demonstrate that NMR and pathology data can be obtained from the same intact
      specimens, and report for the first time a linear correlation between the NMR
      measured concentration of spermine, a proposed endogenous inhibitor to prostate
      cancer growth, and the volume percentage of normal prostatic epithelial cells as
      quantified by histopathology. Our results show that NMR may serve as a critical
      tool for the investigation of the inhibitory mechanism of spermine in human
      subjects.

PMID- 11297744
TI  - CCAAT/enhancer-binding protein beta is required for activation of genes for
      ornithine cycle enzymes by glucocorticoids and glucagon in primary-cultured
      hepatocytes.
AB  - Transcription of genes for enzymes of the ornithine cycle is activated by
      hormones such as glucocorticoids and glucagon. Promoters and enhancers of several
      genes for the enzymes interact with the CCAAT/enhancer-binding protein (C/EBP)
      family of transcription factors, and C/EBPbeta has been suggested to mediate
      glucocorticoid response of the gene for arginase, the last enzyme of the cycle.
      To determine the contribution of C/EBPbeta to hormonal regulation of genes for
      ornithine cycle enzymes, we examined mice with targeted disruption of the
      C/EBPbeta gene. Induction of genes for the enzymes by intraperitoneal injection
      of dexamethasone and glucagon was almost intact in the liver of C/EBPbeta
      deficient mice. On the other hand, in primary-cultured hepatocytes derived from
      C/EBPbeta-deficient mice, induction of genes for the first enzyme
      carbamylphosphate synthetase, as well as for arginase, in response to
      dexamethasone and/or glucagon was severely impaired. Therefore, C/EBPbeta is
      required for hormonal induction of the genes for ornithine cycle enzymes in
      primary-cultured hepatocytes, while the deficiency of C/EBPbeta is compensated
      for in vivo.

PMID- 11297746
TI  - Diacylglycerol effects on phosphatidylinositol-specific phospholipase C activity
      and vesicle fusion.
AB  - Diacylglycerol increased the hydrolytic activity of phosphatidylinositol-specific
      phospholipase C on large unilamellar vesicles containing 5-40%
      phosphatidylinositol. Moreover, diacylglycerol increased the rate and extent of
      vesicle fusion (contents mixing) induced by the enzyme. Kinetic studies of
      intervesicular lipid mixing revealed that fusion was limited by the frequency of
      contacts involving two diacylglycerol-rich domains.

PMID- 11297747
TI  - Lysophosphatidic acid-independent platelet activation by low-density lipoprotein.
AB  - Mildly oxidized low-density lipoprotein activates platelets through
      lysophosphatidic acid (LPA). Hence, the platelet-activating properties attributed
      to native low-density lipoprotein (nLDL) might be caused by LPA contamination. We
      show that nLDL enhances thrombin receptor-activating peptide (TRAP)-induced
      fibrinogen binding to alpha(IIb)beta(3). The LPA receptor blocker N-palmitoyl-L
      serine-phosphoric acid did not affect nLDL-enhanced fibrinogen binding induced by
      TRAP, but reduced TRAP-induced binding. cAMP and inhibitors of protein kinase C
      and Ca(2+) rises completely blocked ligand binding by TRAP and nLDL/TRAP.
      Inhibitors of p38(MAPK) and ADP secretion interfered only partially. Blockade of
      Rho-kinase increased ligand binding 2-3-fold. We conclude that nLDL enhances TRAP
      induced fibrinogen binding independent of LPA.

PMID- 11297748
TI  - The epithelial Na(+) channel (ENaC) is related to the hypertonicity-induced Na(+)
      conductance in rat hepatocytes.
AB  - The epithelial Na(+) channel (ENaC) is composed of the subunits alpha, beta, and
      gamma [Canessa et al., Nature 367 (1994) 463-467] and typically exhibits a high
      affinity to amiloride [Canessa et al., Nature 361 (1993) 467-470]. When expressed
      in Xenopus oocytes, conflicting results were reported concerning the osmo
      sensitivity of the channel [Ji et al., Am. J. Physiol. 275 (1998) C1182-C1190;
      Hawayda and Subramanyam, J. Gen. Physiol. 112 (1998) 97-111; Rossier, J. Gen.
      Physiol. 112 (1998) 95-96]. Rat hepatocytes were the first system in which
      amiloride-sensitive sodium currents in response to hypertonic stress were
      reported [Wehner et al., J. Gen. Physiol. 105 (1995) 507-535; Wehner et al.,
      Physiologist 40 (1997) A-4]. Moreover, all three ENaC subunits are expressed in
      these cells [Bohmer et al., Cell. Physiol. Biochem. 10 (2000) 187-194]. Here, we
      injected specific antisense oligonucleotides directed against alpha-rENaC into
      single rat hepatocytes in confluent primary culture and found an inhibition of
      hypertonicity-induced Na(+) currents by 70%. This is the first direct evidence
      for a role of the ENaC in cell volume regulation.

PMID- 11297749
TI  - Thrombin-thrombomodulin activation of protein C facilitates the activation of
      progelatinase A.
AB  - The activation of the matrix metalloproteinase progelatinase A (MMP-2) has been
      of keen interest because an increase in MMP-2 activity has been implicated in
      disease states such as cancer and atherosclerosis. Activation of MMP-2 occurs on
      the surface of specific cell types in two steps. In the first step, primary
      cleavage of MMP-2 by a membrane-type matrix metalloproteinase generates an
      intermediate. A secondary cleavage and activation of the intermediate is thought
      to occur autocatalytically. Previous studies have shown that thrombin can also
      activate progelatinase A in the presence of endothelial cells. We show that this
      cell-dependent mechanism of MMP-2 activation also occurs with THP-1 cells and
      involves binding of thrombin to thrombomodulin present on the cell surface and
      generation of the anti-coagulant protein, activated protein C. We demonstrate
      that activated protein C is directly responsible for activation and cleavage of
      the gelatinase A intermediate. This work contributes new mechanistic insights
      into the activation of MMP-2 and provides a novel link between matrix
      metalloproteinase activation and anti-coagulation.

PMID- 11297751
TI  - Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B,
      procarboxypeptidase R, procarboxypeptidase U).
AB  - Recently, a new inhibitor of fibrinolysis was described. This inhibitor
      downregulated fibrinolysis after it was activated by thrombin, and was therefore
      named TAFI (thrombin-activatable fibrinolysis inhibitor; EC 3.4.17.20). TAFI
      turned out to be identical to previously described proteins, procarboxypeptidase
      U, procarboxypeptidase R, and plasma procarboxypeptidase B. In this overview, the
      protein will be referred to as TAFI. TAFI is a procarboxypeptidase and a member
      of the family of metallocarboxypeptidases. These enzymes are circulating in
      plasma and are present in several tissues such as pancreas. In this review, we
      will describe the properties of basic carboxypeptidases with the emphasis on the
      role of TAFI in coagulation and fibrinolysis. It cannot be ruled out, however,
      that TAFI has other, yet undefined, functions in biology.

PMID- 11297752
TI  - Changes in hemostasis during treatment of hypertriglyceridemia with a diet rich
      in monounsaturated and n-3 polyunsaturated fatty acids in comparison with a low
      fat diet.
AB  - High levels of fibrinogen, factor (F) VIIc, plasminogen activator inhibitor-1
      (PAI-1), and plasma viscosity are associated with an increased coronary risk. As
      positive correlations of these parameters with triglycerides have been shown, the
      increased coronary risk associated with high levels of triglycerides may be
      assumed to be due to alterations within the hemostatic system. To reduce the
      coronary risk to which hypertriglyceridemic patients are exposed, dietary
      treatment is recommended; the optimal composition of such a diet is, however, a
      matter of debate. With regard to the effects on hemostasis, we compared in a
      sequential approach two diets for treatment of 25 nonobese male patients (age,
      mean+/-S.D., 40.4+/-8.7 years) with fasting triglycerides >2.3 mmol/l. The first
      diet (high fat) was rich in monounsaturated fatty acids (MUFA) and marine n-3
      polyunsaturated fatty acids (PUFA), whereas the second diet (low-fat) was rich in
      complex carbohydrates and dietary fiber. The high-fat diet induced a significant
      lowering of FIIc, FIXc, FXc, FVIIc, FVIIa, FXIIa, PAI-1, plasma viscosity, and
      platelet activity, but led to an increase in fibrinogen, whereas the low-fat diet
      lowered FXIIc values and induced a nonsignificant decrease in fibrinogen.
      Probands on this diet had a slightly higher FVIIa and platelet activity than
      those on the high-fat diet. However, as all changes appeared to be within the
      normal range of each hemostatic parameter, it remains to be clarified whether the
      likely beneficial effects of the high-fat diet on most hemostatic factors are
      outweighed by the small increase in fibrinogen levels.

PMID- 11297753
TI  - Factor VII, tissue factor pathway inhibitor, and monocyte tissue factor in
      diabetes mellitus: influence of type of diabetes, obesity index, and age.
AB  - Changes of the tissue factor (TF) pathway of blood coagulation have been
      described in diabetes and could be involved in its vascular complications. In
      order to evaluate the influence of the type of diabetes and of the obesity index
      and age on these changes, factor VII coagulant activity, factor VII antigen,
      activated factor VII, monocyte TF expression, and plasma Tissue Factor Pathway
      Inhibitor (TFPI) were examined in 18 Type 1 and 16 Type 2 diabetic patients
      compared to non-diabetic control subjects matched for age, sex, and obesity index
      (Types 1 and 2 controls, respectively). Multicomplicated patients were excluded.
      FVIIc, FVIIAg, and FVIIa were higher in Type 2 diabetic patients and controls
      than in Type 1 diabetic patients and controls (P< .03). However, FVIIc and FVIIAg
      were lower in diabetic patients than in their matched controls (P< .03). Monocyte
      expression of TF was not different between Types 1 and 2 diabetic patients and
      their matched controls except for LPS-stimulated monocyte TF activity which was
      lower in Type 2 diabetic patients than in Type 2 controls (P< .05). Plasma TFPI
      was slightly but significantly higher in Type 1 diabetic patients than in Type 1
      controls (P= .01) and was correlated to glycemia. However, both in Type 2
      diabetic patients and controls, TFPI was higher than in Type 1 controls and was
      correlated with BMI (P< .0003). These results indicate that in not
      multicomplicated patients, the increase of FVII and TFPI was highly dependent on
      obesity index and age rather than on diabetes by itself.

PMID- 11297754
TI  - In hemophilia A and autoantibody inhibitor patients: the factor VIII A2 domain
      and light chain are most immunogenic.
AB  - Factor VIII (fVIII) is a protein cofactor essential for blood coagulation, and it
      binds in the factor Xase complex to factors IXa, X, and phospholipid. In about
      30% of severe hemophilia A patients, treatment with fVIII leads to production of
      anti-fVIII antibodies. Anti-fVIII autoantibodies also rarely appear in normal
      individuals. Those antibodies that inactivate fVIII (inhibitors) prevent optimal
      fVIII therapy. Inhibitor epitopes were previously localized to the fVIII A2, A3,
      and C2 domains and to an acidic amino acid region between A1 and A2. Such anti
      fVIII antibodies interfere with fVIII binding to components of the factor Xase
      complex and prevent blood coagulation. When total anti-fVIII titers were
      determined for each fVIII domain in 43 inhibitor plasmas by immunoprecipitation
      (IP) and inhibitor neutralization assays, the anti-light chain (LCh) antibody
      titer was highest, anti-A2 was intermediate, and anti-A1 and anti-B were low. The
      relative immunogenicity of the fVIII domains in hemophilic and autoantibody
      inhibitor patients was similar.

PMID- 11297755
TI  - A novel splice acceptor site mutation of protein S gene in affected individuals
      with type I protein S deficiency: allelic exclusion of the mutant gene.
AB  - Sequencing studies of the protein S gene (PROS1) in a Japanese patient suffering
      from recurrent thrombosis revealed the following. The proband and his first
      daughter, but not the second daughter, were having the type I protein S (PS)
      deficiency due to a novel point mutation from A to G at the intronic acceptor
      splice site in intron 13 of the PROS1. In the affected daughter, exclusion of the
      aberrant allele was assessed by the BstX1 dimorphism of PROS1 at Pro626
      (CCG/CCA). The reduced PS activities in the proband and his first daughter were
      apparently due to defective production of mRNA from the mutant allele.

PMID- 11297756
TI  - Anti-human vWF monoclonal antibody, AJvW-2 Fab, inhibits repetitive coronary
      artery thrombosis without bleeding time prolongation in dogs.
AB  - The antithrombotic and antihaemostatic effects of the monoclonal antibody against
      human vWF (AJvW-2 Fab) were investigated in comparison with those of the
      monoclonal antibody against platelet GPIIb/IIIa (abciximab) in dogs. The ex vivo
      platelet aggregation and template bleeding time were measured before, 5, 90, 210
      min and 24 h after injection of either AJvW-2 Fab or abciximab in anesthetized
      beagle dogs. Plasma concentration, vWF occupancy and plasma vWF antigen level
      were also measured by ELISA. In addition, the antithrombotic effect was evaluated
      in a canine model of repetitive coronary thrombosis (Folts model). AJvW-2 Fab
      significantly inhibited the ex vivo botrocetin-induced platelet aggregation at
      0.18 mg/kg (53% plasma vWF occupancy) and also inhibited cyclic flow reductions
      (CFRs) at 0.06 mg/kg (31% occupancy). A significant prolongation of the bleeding
      time was observed at 1.8 mg/kg (95% occupancy), which was 30 times as high as the
      antithrombotic effective dose. Whereas, abciximab significantly inhibited both
      the ex vivo ADP-induced platelet aggregation and CFRs at 0.8 mg/kg, which was the
      minimally effective dose, also resulting in a significant prolongation of the
      bleeding time. These results suggest that blockade of the GPIb-vWF axis with AJvW
      2 Fab leads to the inhibition of thrombus formation in the stenosed coronary
      arteries without less bleeding time prolongation than the GPIIb/IIIa blockade
      with abciximab.

PMID- 11297757
TI  - Domain specific monoclonal anti-factor VIII antibodies generated by inclusion
      body-renatured factor VIII peptides.
AB  - Production of monoclonal anti-factor VIII (FVIII) antibodies was hampered by the
      availability of FVIII proteins devoid of albumin and the von Willebrand factor
      (vWF). We showed a successful way to generate domain specific anti-FVIII
      antibodies by using a series of Escherichia coli expressed FVIII fusion peptides.
      A total of eight fusion peptides were synthesized to cover almost the entire
      coding region of FVIII. All except one of the fusion peptides were insoluble and
      became aggregated as inclusion bodies. Purification and refolding of the peptides
      were accomplished by solublizing them with denaturants and dialyzing them in
      appropriate buffers, this being followed by chromatography of the refolded
      fractions on a metal-ion chelating column. These purified FVIII fusion peptides
      were used individually or as a pool to immunize mice and generate antibodies.
      Three monoclonal antibodies, D2, E6 and B12, were obtained. D2 recognizes a
      region (residues 1680-1703) of the light chain of FVIII, E6 recognizes a fragment
      (residues 744-1021) in the heavy chain, and B12, the A1 domain (residues 89-326).
      Both D2 and B12 inhibited >80% FVIII function. The affinities (k(A)) of the
      antibodies for FVIII were 1.62x10(7) M(-1) for D2 and 2.2x10(8) M(-1) for E6.
      Although B12 is inhibitory, it did not show a strong binding affinity with FVIII.
      The specificity of D2 and E6 for FVIII was demonstrated by immunoprecipitation of
      the FVIII protein in full-length recombinant FVIII (rFVIII) supplemented FVIII
      deficient plasma, but not in FVIII-deficient plasma alone. An enzyme-linked
      immunosorbant assay (ELISA) using D2 or E6 was designed to detect plasma FVIII.
      The system may be useful in monitoring FVIII in cultured supernatants and in
      mouse models for gene therapy experiments.

PMID- 11297758
TI  - Reduced reactivity towards anti-protamine antibodies of a low molecular weight
      protamine analogue.

PMID- 11297759
TI  - Glutathione S-transferase M1 gene polymorphism in bladder cancer patients. a
      marker for invasive bladder cancer?
AB  - The glutathione S-transferase M1 (GSTM1) gene is polymorphic in humans, and the
      deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous
      absence of the GSTM1 gene, or the "null" genotype (GSTM1, 0/0). The increased
      risk of bladder cancer has been shown to correspond with this gene defect. No
      reports, however, have been found in the literature regarding GSTM1 gene
      deficiency with superficial and invasive bladder cancer. In this study, we
      examined the association of the GSTM1-null genotype with superficial and invasive
      bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined
      the frequency of the GSTM1 gene defect in Turkish patients with superficial
      bladder cancer (N = 61), invasive bladder cancer (N = 42), and control subjects
      (N = 202) who had no history of cancer. The GSTM1 null genotype was observed in
      34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR:
      2.246; 95% CI: 1.384-3.645, P: 0.00094). In other words, the presence of the
      GSTM1-null genotype significantly increased the risk of bladder cancer
      development. Among invasive bladder cancers, the frequency of the GSTM1-null
      genotype was 64.3% (OR: 0.294, 95% CI: 0.147-0.590, P: 0.0003). This was also
      significantly higher than control subjects, indicating that patients carrying
      this genotype were at increased risk for developing invasive bladder cancer. This
      relationship was not statistically significant in the superficial bladder cancer
      group (OR: 0.585, 95% CI: 0.327-1.045, P: 0.06). Our results indicate that GSTM1
      gene polymorphism should be considered as an important risk modifier in the
      development of bladder cancer and might be used as a predictive marker for
      invasive bladder cancer.

PMID- 11297760
TI  - Microdissection and reverse painting in a melanoma cell line: a detailed
      description of structurally abnormal chromosomes.
AB  - Seven structurally abnormal chromosomes from a newly established melanoma cell
      line were microdissected. The DNA from these chromosomes was DOP amplified and
      labeled with Biotin or Digoxigenin for FISH analysis. The complex nature of these
      markers is described.

PMID- 11297761
TI  - Case of lipoblastoma with two derivative chromosomes 8 containing homogeneously
      staining-like regions and a review of the literature: lipoblastoma and chromosome
      8.
AB  - We report a case of a lipoblastoma in a 10-month-old girl in which the
      cytogenetic aberration showed a homogeneously staining-like region (hsr) within
      two derivative chromosomes 8. There was a loss of one normal copy of chromosome 8
      and gain of two identical derivative chromosomes 8 with the karyotype designation
      47,XX,psu idic(8)(pter-->q12 approximately 13::hsr::q12 approximately 13-
      >pter),+psu idic (8)(pter-->q12 approximately 13::hsr::q12 approximately 13-
      >pter). This is the first report of a chromosomal aberration of this type seen in
      lipoblastoma.

PMID- 11297762
TI  - Tetrasomy 8 is associated with a major cellular proliferative advantage and a
      poor prognosis. two cases of myeloid hematologic disorders and review of the
      literature.
AB  - We report two cases of acute myeloid leukemia (AML) with tetrasomy 8 detected in
      patients' bone marrow samples using chromosome GTG-banding, fluorescence in situ
      hybridization (FISH) and primed in situ labeling (PRINS) techniques. Case 1 was a
      myelodysplastic syndrome (MDS) in transition to AML-M4 and case 2 was an AML-M2.
      In case 1, the tetrasomy 8 was found in 40% of metaphase cells and constituted
      the only chromosome abnormality. In case 2, it was accompanied by a double Ph,
      trisomy 18 and disomy Y and was found in 68% of metaphase cells. However, FISH
      and PRINS techniques revealed the coexistence of tetrasomy 8 and trisomy 8 in
      interphase nuclei of both cases. When the proportion of cells with tetrasomy 8
      was compared between metaphases and interphase nuclei, it showed a much higher
      percentage of cells with tetrasomy 8 in metaphases than in interphase nuclei.
      Moreover, in case 2, although multi-PRINS and FISH-PRINS techniques showed other
      populations of interphase nuclei with different combinations of chromosome
      anomalies with respect to the copy numbers for chromosomes 8, 18, Y and Ph, only
      cells that contained either a single Ph or tetrasomy 8 plus trisomy 18, disomy Y,
      and double Ph could be seen in metaphases. This strongly suggests that tetrasomy
      8 confers a higher proliferative advantage to cells. Our cases also show that the
      tetrasomy 8 is associated with a poor prognosis.

PMID- 11297763
TI  - PTEN/MMAC1 in malignant melanoma and its importance for tumor progression.
AB  - A novel tumor suppressor gene, PTEN/MMAC1, on 10q23, displayed a number of
      mutations in solid tumors as gliomas and breast cancer. Aberrations of the long
      arm of chromosome 10 have been frequently detected in tumor progression of
      malignant melanoma of the skin by a variety of methods including cytogenetic
      analysis, fluorescence in situ hybridization and loss of heterozygosity analysis.
      Compared to previous studies, which propose an involvement of PTEN/MMAC1 in
      malignant melanoma mostly on the basis of data derived from cell lines and
      metastases, we analyzed a broader spectrum of exclusively patient derived tumor
      tissue by PCR and direct sequencing analysis of PTEN/MMAC1. Here, we present data
      of 25 primary melanomas (8 superficial spreading melanomas, 17 nodular melanomas)
      and 25 metastases of 41 patients. Neither loss of the complete gene nor a whole
      exon nor any nonsense mutations could be demonstrated. However, we detected
      several polymorphisms and some mutations in the introns, and in two metastatic
      tumors mutations with an amino acid change. Our results obtained from tissue
      samples underline that mutations of PTEN/MMAC1 are not an essential event in the
      onset of malignant melanoma of the skin, but could have an impact on tumor
      progression.

PMID- 11297764
TI  - Loss of X chromosome in childhood acute lymphoblastic leukemia.
AB  - We present six cases of childhood acute lymphoblastic leukemia (ALL) in which an
      acquired loss of the X chromosome was detected. The cases derive from a
      consecutive series of 178 childhood ALL, consisting of 80 girls and 98 boys. In
      five cases the presence of the TEL-AML1, t(12;21), fusion product was detected by
      FISH. The single negative case had an unusual t(1;19)(p13;q13). In addition, this
      was the only case that did not have a cytogenetically visible rearrangement
      involving one of the chromosome regions 6q, 9p, or 12p. The six cases showed the
      typical presentation features of an ALL of FAB type L1, a common ALL
      immunophenotype with myeloid marker co-expression, and a median presenting age of
      7 years. We, therefore, conclude that loss of chromosome X may be a secondary
      event in older girls with TEL-AML1-positive ALL.

PMID- 11297765
TI  - Trisomy 8 and monosomy 7 detected in bone marrow using primed in situ labeling,
      fluorescence in situ hybridization, and conventional cytogenetic analyses. A
      study of 54 cases with hematological disorders.
AB  - Trisomy 8 and monosomy 7 are the two most frequent aneuploidies found in
      hematological disorders such as myelodysplastic syndrome (MDS) and acute myeloid
      leukemia (AML). In this study, primed in situ labeling (PRINS), fluorescence in
      situ hybridization (FISH) and conventional cytogenetic approaches were used to
      investigate 54 cases of hematopoietic disorders. Of these cases, there were 22
      cases of trisomy 8, 2 cases of tetrasomy 8, 14 cases of monosomy 7, and 16 cases
      with two copies of both chromosomes 7 and 8. PRINS was carried out in interphase
      nuclei of bone marrow samples using primers that can specifically detect alpha
      satellite DNA sequences of chromosomes 7 and 8. In parallel, using the alpha
      satellite probes for chromosomes 7 and 8, FISH was performed for all the cases.
      PRINS and FISH techniques showed similar specificity and sensitivity. In
      comparison to FISH, PRINS is more advantageous since it is a faster, easier, and
      more cost-effective technique. Additionally, for most of the cases, a higher
      proportion of aneuploidy was detected in metaphases using conventional
      cytogenetics, as compared to the one found in interphase nuclei identified with
      PRINS and FISH techniques. In other words, for these cases, the cells with
      trisomy 8 or monosomy 7, had a distinct proliferative advantage compared to the
      disomic cell population. Therefore, to better quantify the proportion of
      aneuploid cells in bone marrow, we recommend to investigate the frequency of
      aneuploidy in nuclei using PRINS, rather than studying only the dividing cells as
      detected by conventional cytogenetic techniques.

PMID- 11297766
TI  - Genetic heterogeneity and alterations in chromosome 9 loci in a localized region
      of a functional pituitary adenoma.
AB  - The molecular alterations reported in pituitary adenomas include mutations at the
      G(s)alpha in somatotrophinomas, and hypermethylation of the p16 tumor suppressor
      gene. There are, however, no reports of genomic instability or intratumor genetic
      heterogeneity in pituitary adenomas. We have studied the microsatellite loci on
      the short arm of chromosome 9 (9p) and the DNA fingerprinting pattern, of
      adjacent compartments, about 2 mm across, in a functional chromophobe pituitary
      adenoma secreting growth hormone and prolactin. The microsatellite loci were
      studied by PCR amplification using locus specific primers, while the DNA
      fingerprinting pattern was studied by randomly amplified polymorphic DNA (RAPD)
      analysis. Normal leukocyte DNA was taken as control. Only one compartment (Ta)
      showed alterations in several of the microsatellite loci and in the RAPD pattern
      vis a vis corresponding normal DNA and also the other two compartments of the
      tumor. This provides evidence for the localized nature of genomic instability in
      this tumor.

PMID- 11297767
TI  - Telomeric associations and chromosome instability in ataxia telangiectasia T
      cells characterized by TCL1 expression.
AB  - T-cell tumors in ataxia telangiectasia (AT), such as T-PLL/T-CLL, are first
      preceded by the development of a large clone of T-lymphocytes, characterized by
      chromosomal rearrangements, which usually involve specific regions such as the
      14q11 region. Malignancy develops years later, after additional chromosomal
      changes resulting from the genomic instability consequent to ATM disruption and
      to the activation of the TCL1 oncogene. Here we report the results of a
      cytogenetic follow-up of an AT patient (AT94-1), still without signs of
      hematological abnormalities, bearing a T-lymphocyte clone characterized by the
      t(14;14)(q11;q32) rearrangement and having TCL1 expression. We demonstrated that
      in clonal cells TCL1 expression correlates with increasing genomic instability
      and in time this mainly induces chromosomal rearrangements and telomeric
      associations (tas). Chromosome 21 is not randomly involved; in particular, an
      i(21q) indicates that it is a subclone prone to additional genetic changes and
      could represent an early chromosomal rearrangement involved in tumorigenesis.
      With regard to the increase in tas, we observed that: (i) it is inversely
      correlated with the proliferative ability of AT94-1 lymphocytes in PHA-stimulated
      short-term cultures (cell aging in vitro); (ii) this increase is not due to
      changes either in cell radiosensitivity (measured as bleomycin (BML)-sensitivity)
      or due to an illegitimate recombination (measured as adriamycin-sensitivity),
      which may not be sufficient for tumor development.

PMID- 11297768
TI  - Clonal evolution of a radon-induced rat lung tumor.
AB  - Radon gas may represent a source of pulmonary radio-contamination either in mine
      or in domestic conditions. Since epidemiological studies are controversial, as
      long as biological markers of the exposure to such agents will not be identified,
      the question will remain open. We have previously shown a direct dose-dependent
      relationship between lung cancer occurrence and radon inhalation of rats. In this
      study, we report a cytogenetic study of a radon-induced rat lung tumor.
      Chromosome banding and chromosome specific paintings were performed on cultures
      of both fresh and xenografted tumors. We found by analyzing 17 sub-clones that
      all karyotypes presented a translocation involving rat chromosomes (RNO) 8 and
      20, and a terminal deletion of RNO 15p suggesting a monoclonal origin of this
      tumor. RNO 15 is homologous to numerous human chromosomes (HSA), in particular to
      HSA 3p14.2, 3p22-p24.1 and 3p24.2-p24.3, this human chromosome being frequently
      lost in human lung carcinomas. Besides sharing chromosome alteration involving
      common features with those found in human lung cancer, this rat lung carcinoma
      represents a useful model to study tumor progression with respect to clonal
      evolution.

PMID- 11297769
TI  - Chromosome analysis and comparison of the benign cystic and malignant squamous
      component of an ovarian teratoma.
AB  - Teratoma, the most common ovarian germ-cell tumor, presumably arises from a
      single germ cell and is composed of tissues representing all germ layers
      (ectoderm, mesoderm, and endoderm). Benign cystic teratomas (dermoid cyst)
      represent over 95% of ovarian teratomas and are comprised of entirely mature
      adult tissues. When malignant, almost all mature teratomas contain squamous
      carcinoma. We report for the first time the karyotypic comparison of an ovarian
      teratoma in a 36-year-old female with tissue separately taken from the benign
      cystic and malignant squamous components. The malignant squamous component
      revealed two distinct karyotypic populations: one diploid and the other
      polyploid. Both, however, demonstrated two common markers. The polyploid
      population also demonstrated numerous additional abnormalities with multiple
      copies of chromosome 20. Though many of the chromosomal aberrations were unique
      to the benign component, several karyotypes showed the same markers noted in the
      malignant squamous component. The significance of this finding is that it may
      serve to identify those histologically benign teratomas destined to undergo
      malignant transformation.

PMID- 11297770
TI  - Multicolor FISH in chronic lymphocytic leukemia. An interphase study of patients
      with early-onset disease.
AB  - Trisomy 12 and deletions of 13q14.2 and 14q32 are the most common chromosome
      abnormalities in patients with B-chronic lymphocytic leukemia (B-CLL), but
      whether specific chromosomal defects influence the course of B-CLL is still a
      matter of discussion. The aim of our study was to assess the possible correlation
      between cytogenetic findings and clinical characteristics. Thirty patients with
      previously untreated early-onset B-CLL were recruited. The incidence of trisomy
      12, and observations of 13q14.2 and 14q32 was analyzed in unstimulated bone
      marrow cells by means of multicolor interphase FISH. No correlation was found
      between trisomy 12 and the patients' clinical characteristics. The analysis of
      the patients with trisomy 12 and observations of 13q14.2 and 14q32 revealed
      heterogeneity of the leukemic cell population, thus indicating that these
      chromosomal abnormalities are probably a secondary event in CLL leukemogenesis.
      The finding of RB1 gene nullisomy and 14q32 deletions in patients at an advanced
      clinical stage suggests a possible correlation between these rearrangements and
      disease progression. Multicolor FISH analysis in B-CLL provides important
      diagnostic, clinical, and prognostic information that may help in assessing
      prognosis and making treatment decisions.

PMID- 11297771
TI  - New t(11;12)(q12;q11) characterized by RxFISH in a patient with T-cell large
      granular lymphocyte leukemia.
AB  - Chromosomal abnormalities in patients with large granular lymphocyte leukemia
      (LGLL) are rare. Herein we present a novel cytogenetic abnormality
      t(11;12)(q12;q11) in a patient with LGLL identified by cross-species color
      banding (RxFISH). The application of RxFISH allowed the rapid and easy
      identification of a chromosome rearrangement that was not recognized by
      conventional cytogenetics. Therefore, RxFISH is a suitable complement to, but not
      a replacement for, conventional cytogenetics.

PMID- 11297772
TI  - A novel variant three-way translocation of inversion 16 in a case of AML-M4eo
      following low dose methotrexate therapy.
AB  - We report a case of acute myelomonocytic leukemia with eosinophilia (AML-M4eo) in
      a 65-year-old man following low dose methotrexate treatment for pemphigus
      vulgaris. Cytogenetic studies at diagnosis revealed a complex karyotype including
      a reciprocal translocation between 11q14.2 and 16q22, an inversion of chromosome
      16(p13.1q22), and an apparently terminal deletion of 7q31. The presence of
      inv(16) was confirmed by reverse transcription-polymerase chain reaction which
      demonstrated a Type A fusion transcript derived from the core binding factor
      (CBF) beta and the smooth muscle myosin heavy chain (MYH11) genes. The patient
      was in complete hematologic and cytogenetic remission 6 months following
      intensive chemotherapy. Because AML-M4eo with inv(16) has a favorable prognosis,
      molecular studies should be performed in case the identification of inv(16) by
      conventional cytogenetics is difficult due to a complex karyotype.

PMID- 11297774
TI  - Development and functions of seed transfer cells.
AB  - In secretion or absorption processes, solutes are transported across the
      plasmalemma between the symplastic and apoplastic compartments. For this purpose,
      certain plant cells have developed a specialised transfer cell morphology
      characterised by wall ingrowths, which amplify the associated plasmalemma surface
      area up to 20-fold. Detailed studies on the function and development of transfer
      cells in the context of seed filling have been carried out mainly in cereal
      endosperm, and for the cotyledon and seed coat cells of legumes. The major
      solutes transferred are amino acids, sucrose and monosaccharides. The
      contributions of recently identified symporter proteins to solute transfer are
      reviewed here, as is the role of apoplastic invertases in promoting solute
      assimilation. Expression of invertase and monosaccharide transporters early in
      both cereal and legume seed development orchestrates the distribution of free
      sugars which play an important role in regulating transfer cell function and
      determining final endosperm or embryo cell number. Transfer cell differentiation
      is subject to developmental control, and may also be modulated by sugar levels.
      The most abundant genes specifically expressed in the transfer layer of maize
      endosperm encode small antipathogenic proteins, pointing to a role for these
      cells in protecting the developing endosperm against pathogen ingress. The
      functional characterisation of the corresponding transfer layer-specific
      promoters has provided a tool for dissecting transfer cell functions. Transfer
      cells are highly polar in their organisation, the characteristic cell wall
      ingrowths developing on one face only. The presence of cytoskeletal components
      bordering wall ingrowths is documented, but their role in establishing transfer
      cell morphology remains to be established.

PMID- 11297775
TI  - Effects of Sodium Chloride on plant cells; a 31P and 23Na NMR system to study
      salt tolerance.
AB  - In plant cells, the Na(+)/H(+) antiport at the tonoplast provides a biochemical
      pathway to transport cytoplasmic Na(+) into the vacuole. Recently it was shown
      that overexpression of a vacuolar Na(+)/H(+) promotes sustained plant growth at
      high NaCl levels (Apse et al. Science 285, 1256, 1999). The sequestration of
      Na(+) ions into the vacuole can be followed using 31P and 23Na NMR spectroscopy.
      Suspension cell cultures are very suitable for this purpose and allow rapid and
      accurate assessment of the activity of the Na(+)/H(+) antiport and therefore
      potentially of salt tolerance. Perfusion experiments with maize cells that are
      not particularly salt (NaCl) tolerant showed that during salt stress the
      cytoplasmic pH remains unchanged while the vacuolar pH significantly increased.
      During Na(+) sequestration into the vacuole, the cytoplasmic pH equilibrates
      faster than that of the vacuole. Both vacuolar pH and the cellular Na(+) uptake
      rate were dependent on extracellular Na(+) for concentrations up to approximately
      300 mM. For Na(+) concentrations >/=300 mM, both vacuolar pH and cellular Na(+)
      uptake became independent of the extracellular concentration. This indicates
      either a saturation of Na(+) uptake at the cell surface or a saturation of the
      Na(+)/H(+) transporter at the tonoplast. Na(+) uptake into the cell is
      accompanied by a rapid increase in vacuolar PO(4)(3-), broadening of the 31P
      resonances and a reduction in glucose monophosphate and UDPG.

PMID- 11297776
TI  - Purification and characterisation of a beta-glucosidase abundantly expressed in
      ripe sweet cherry (Prunus avium L.) fruit.
AB  - A beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) was purified to
      homogeneity from ripe fruits of sweet cherry (Prunus avium L.) by ammonium
      sulphate precipitation, ion exchange and size exclusion chromatography. The
      enzyme is a monomer with a molecular mass of approximately 68 kDa and an acidic
      isoelectric point. N-terminal sequence analysis indicated that sweet cherry beta
      glucosidase is related to other plant cyanogenic beta-glucosidases. Substrate
      specificity studies revealed that the enzyme is able to attack and hydrolyse
      several synthetic substrates and total cell walls purified from ripe fruit.
      Biochemical and immunolocalisation studies showed that sweet cherry beta
      glucosidases are mainly localised in the cytosol and in the apoplast, at the
      unripe stage of ripening; in ripe fruit it is also associated with cell wall.

PMID- 11297777
TI  - Characterization of the mitochondrial nad7 gene in Physcomitrella patens:
      Similarity with angiosperm nad7 genes.
AB  - The nad7 gene, encoding the subunit 7 of NADH dehydrogenase complex I, is located
      in the mitochondrial genome in some species of green algae and seed plants, while
      it is nuclear-encoded in fungi and animals. In a liverwort, the presence of a
      mitochondrial nad7 pseudogene, and a nuclear nad7 gene has been reported. We have
      isolated the mitochondrial nad7 gene of the moss Physcomitrella patens. This gene
      is transcribed as a monocistronic mRNA and contains two group II introns that
      correspond to the first two of the four introns in the nad7 genes in angiosperms.
      Results of phylogenetic analysis supported monophyly of the nad7 genes of mosses
      and tracheophytes. Available data suggest that the nuclear transfer of the nad7
      gene occurred only in the liverwort lineage, which diverged extensively from the
      mosses and tracheophytes with respect to the nad7 gene.

PMID- 11297778
TI  - Purification of an osmotin-like protein from the seeds of Benincasa hispida and
      cloning of the gene encoding this protein.
AB  - A pathogenesis-related (PR) protein was purified from the seeds of Benincasa
      hispida, which is a medicinal plant and a member of the Cucurbitaceae family.
      Purification was achieved by using a procedure consisting of an acid treatment
      step followed by two chromatography steps. The protein is a basic protein with
      molecular mass of approximately 28 kDa. The sequences of the N-terminal 30 amino
      acids and four peptides generated from protease digestion were determined. These
      sequences indicated that the protein is an osmotin-like protein (OLP). Osmotin
      and OLPs are members of the thaumatin-like, PR-5 family of the PR proteins. A
      genomic clone of the gene encoding the protein was isolated and sequenced. The
      predicted protein has a signal peptide of 18 amino acids, and the mature protein
      has a molecular mass of 24.8 kDa with an isoelectric point of 7.67. The protein
      has 17 cysteine residues, of which 16 appear in the same positions as those
      appear in the sweet-tasting protein thaumatin and several other thaumatin-like
      proteins. Southern hybridization analysis indicated that the gene encoding the
      protein is a single copy gene. A computer-generated, three-dimensional model of
      the protein is presented.

PMID- 11297779
TI  - Molecular phylogeny of the genus Kalanchoe (Crassulaceae) inferred from
      nucleotide sequences of the ITS-1 and ITS-2 regions.
AB  - The study presents an analysis of genotypic diversity in the genus Kalanchoe
      (Crassulaceae) on the level of Internal Transcribed Spacer (ITS) sequences and
      the attempt to correlate this diversity with previous findings on
      ecophysiological behavior, habitat preference, infrageneric taxonomic position of
      the species and DNA polymorphism derived from RAPD-PCR data. The Kalanchoe
      species are mainly abundant in Madagascar and eastern continental Africa and
      perform in situ diverse modes of crassulacean acid metabolism (CAM), an
      ecophysiologically relevant adaptation of photosynthesis. Total DNA was extracted
      from 68 Kalanchoe species and varieties. The ITS-1 and ITS-2 regions of the
      nuclear RNA genes were amplified by polymerase chain reaction, cloned and
      sequenced. The alignments of the sequences were evaluated by distance (neighbor
      joining) and character state (maximum parsimony) methods. The main topologies of
      the obtained ITS phylogenetic trees were quite similar irrespective of the mode
      of evaluation and show: (A) within the Crassulaceae the genus Kalanchoe forms a
      monophyletic clade; and (B) within the genus the species form three main clusters
      which coincide well with the previously reported three infrageneric sections of
      the species distinguishable by classical taxonomic criteria, the mode of in situ
      CAM performance, and DNA fragment pattern obtained by RAPD-PCR analyses.
      Moreover, the ITS phylogenetic trees show that all African Kalanchoe species form
      a distinct group within the most derived of the three main clusters. This is
      consistent with the view that the center of phylogenetic radiation of the genus
      is located in Madagascar from where the species have spread into the continental
      Africa.

PMID- 11297780
TI  - Transformation of Japanese persimmon (Diospyros kaki Thunb.) with apple cDNA
      encoding NADP-dependent sorbitol-6-phosphate dehydrogenase.
AB  - Japanese persimmon (Diospyros kaki Thunb. cv Jiro) was transformed with apple
      (Malus x domestica Borkh.) cDNA encoding NADP-dependent sorbitol-6-phosphate
      dehydrogenase (S6PDH) by an Agrobacterium-mediated leaf-disc transformation
      system. Integration and expression of the transgene were confirmed by genomic DNA
      blot and immunoblot analyses. Sorbitol accumulation in five of six transgenic
      plants obtained was confirmed by GC-MS. The amount of sorbitol in the leaves of
      transgenic plants varied from 14.5 to 61.5 umol g(-1) fr wt(-1). Sorbitol was not
      found in leaves of non-transformed 'Jiro' or the line PS7 that produced S6PDH
      protein with no S6PDH activity. Eventually, two transformed lines producing high
      (PS1) and medium (PS6) amounts of sorbitol, one control transformed line (PS7),
      and non-transformed 'Jiro' were selected and evaluated for salt-stress tolerance.
      Under NaCl stress, the activity of photosystem II in leaves was determined in
      terms of the ratio of the variable (Fv) to the maximum (Fm) fluorescence of
      chlorophyll. The rate of decline in Fv/Fm under NaCl stress was lower in PS1 than
      the other three lines, suggesting that PS1 is more tolerant to NaCl stress than
      the other three lines. The factors that caused enhanced salt stress tolerance in
      PS1 are discussed in relation to sorbitol biosynthesis and its growth.

PMID- 11297781
TI  - Catalase deficiency reduces survival and pleiotropically affects agronomic
      performance in field-grown barley progeny.
AB  - Field-grown plants of the catalase-deficient mutant RPr79/4 show necrotic lesions
      in leaves and preferentially die. Initially, necrotic lesions exhibited by
      RPr79/4 were used to indirectly assess the role of distinct levels of catalase on
      the survival and agronomic performance of field-grown barley progeny. The
      segregation of three control traits was also analyzed to eliminate the influence
      of any obvious meiotic disturbance in case a reduction of plant survival was
      observed. The RPr79/4 necrotic phenotype had recessive expression in field-grown
      F1 plants. F2 progeny studies performed in the greenhouse revealed that the
      inheritance of necrotic lesions was monofactorial, and that the control traits
      segregated as expected. Progeny test analyses of field-grown F2 plants
      demonstrated that necrotic homozygous plants died preferentially. While the few
      surviving necrotic homozygous families were catalase-deficient, healthy
      homozygous families had normal levels of catalase. Progeny test analyses of the
      control traits confirmed the inheritance calculated in F2. Taken together, these
      findings indicate that abnormal segregation of necrotic lesions cannot be
      attributed to any obvious abnormal meiotic behavior but to the incapacity of
      catalase-deficient plants to overcome field stress conditions. Thus, catalase
      deficiency in barley reduced survival and pleiotropically affected the agronomic
      performance by diminishing seed weight and yield.

PMID- 11297782
TI  - Hyperhydricity in in vitro eggplant regenerated plants: structural
      characteristics and involvement of BiP (Binding Protein).
AB  - The hyperhydricity in eggplant (Solanum melongena L.) plants was monitored by the
      induction of the ER-luminal resident protein BiP. Although tissue culture
      conditions may induce BiP synthesis, the accumulation of BiP in hyperhydric
      shoots was consistently higher than in non-hyperhydric shoots. The leaf and stem
      anatomy in non-hyperhydric and hyperhydric eggplant was investigated aiming to
      identify structural changes associated with this phenomenon. In non-hyperhydric
      organs there were smaller and more organized cells, besides a more differentiated
      vascular system when compared with its hyperhydric counterpart. Scanning electron
      microscopy of leaves showed that leaf surface and stomata differentiation were
      also affected in hyperhydric plants.

PMID- 11297783
TI  - Arginine decarboxylase transgene expression and analysis of environmental stress
      tolerance in transgenic rice.
AB  - Arginine decarboxylase (ADC) cDNA from oat (Avena sativa L.) was introduced into
      rice (Oryza sativa L.) genome by an Agrobacterium-mediated transformation method.
      Expression of the ADC transgene under the control of an ABA-inducible promoter
      led to stress-induced upregulation of ADC activity and polyamine accumulation in
      transgenic rice plants. Second-generation (Rl) transgenic rice plants showed an
      increase in biomass under salinity-stress conditions, as compared to the non
      transformed control plants.

PMID- 11297784
TI  - Expression of a bifunctional green fluorescent protein (GFP) fusion marker under
      the control of three constitutive promoters and enhanced derivatives in
      transgenic grape (Vitis vinifera).
AB  - Activity of three constitutive promoters and enhanced derivatives in transgenic
      grape (Vitis vinifera L. cv. Thompson Seedless) was characterized using a
      bifunctional fusion marker containing the enhanced green fluorescent protein
      (EGFP) and neomycin phosphotransferase (NPTII) genes. Relative differences in
      transient GFP expression and stable transformation efficiencies were used to
      compare promoter activity. Expression patterns in transformed somatic embryos
      revealed that the ACT2 promoter from Arabidopsis thaliana, previously shown to be
      a strong constitutive promoter in A. thaliana and other species, failed to
      promote strong expression in grape. In contrast, a promoter isolated from cassava
      vein mosaic virus (CsVMV) supported high levels of transgene expression
      equivalent to those achieved using an enhanced double cauliflower mosaic virus
      (CaMV) 35S promoter. Duplication of the 5'-upstream enhancer region of the CsVMV
      promoter further enhanced its ability to increase transgene expression. However,
      the pattern of transgene expression driven by these two viral promoters was
      significantly different at the whole plant level. The enhanced double CaMV 35S
      promoter was highly active in most tissues and organs including roots, mature
      leaves, shoot apices and lateral buds. In contrast, the CsVMV promoter and its
      double enhancer derivative induced relatively weak expression in these tissues.
      Our results suggest that activity of the CsVMV promoter, in contrast to the CaMV
      35S promoter, was under developmental regulation in transgenic grape plants as
      compared with the CaMV 35S promoter.

PMID- 11297785
TI  - Transformation of peanut (Arachis hypogaea L.) with tobacco chitinase gene:
      variable response of transformants to leaf spot disease.
AB  - Fertile transgenic plants of peanut (Arachis hypogaea L.) cv. TMV-2 expressing
      tobacco chitinase and neomycin phosphotransferase (npt II) genes were generated
      using an Agrobacterium tumefaciens (LBA4404/pBI121-pBTex)-mediated transformation
      system. A tissue culture-independent method wherein embryo in the mature seed is
      inoculated and reared into single plant transformant was used for transformation.
      Southern blot analysis of genomic DNA isolated from T(0) transformants and
      progeny plants (T(1)) demonstrated that the transgenes are stably integrated in
      the genome of transgenic peanut plants and inherited by the offspring. The
      expression of the heterologous chitinase gene driven by CaMV 35S promoter led to
      a high level of activity in some of the transgenic plants. Small-scale field
      tests indicated increased ability of these plants to resist the fungal pathogen
      Cercospora arachidicola (the causal organism of the leaf spot or Tikka disease of
      peanut), which is an important peanut pathogen. These results suggest that a
      heterologous chitinase gene was functional in peanut and expressed in healthy
      plants. The study also shows that peanut plants containing transgenically
      increased activity of chitinase were resistant to attack by the fungal pathogen
      C. arachidicola to different degrees. The strategy employed may be useful for the
      control of other fungal diseases of the crop.

PMID- 11297786
TI  - Relative quantitative RT-PCR to study the expression of plant nutrient
      transporters in arbuscular mycorrhizas.
AB  - The influence of arbuscular mycorrhizal fungi (AMF) on the expression of plant
      nutrient transporters was studied using a relative, quantitative reverse
      transcription polymerase chain-reaction (RQRT-PCR) technique. Reverse-transcribed
      18S rRNA was used to standardize the treatments. The technique had high
      reproducibility and reflected trends in gene expression as observed by Northern
      blotting. Using this technique, it was demonstrated that both the high-affinity
      phosphate transporter MtPt2 and a putative nitrate transporter from Medicago
      truncatula were down-regulated in roots when colonized by some, but not all AMF.
      Colonization by the AMF Glomus rosea, in particular, failed to strongly down
      regulate these plant genes within the root. This technique may be suitable for
      the study of plant genes in mycorrhizal roots when Northern blotting is not
      possible due to low gene expression or when limited amounts of tissue are
      available for study.

PMID- 11297787
TI  - Plant hormone regulation on scopoletin metabolism from culture medium into
      tobacco cells.
AB  - Tobacco (Nicotiana tabacum L. Bright Yellow) T-13 cell line has an ability for
      production of scopoletin. In this cell culture, scopoletin is taken up from
      culture medium and accumulated in vacuoles after conversion to scopolin when
      cells are treated with 2,4-dichlorophenoxyacetic acid (2,4-D) (Taguchi et al.
      (2000)). To clarify the effect of 2,4-D on tobacco cells, its interaction with
      several other plant hormones was investigated. Other auxins also stimulated the
      uptake in the same manner as 2,4-D did, although higher concentrations were
      required than that of 2,4-D. When p-chlorophenoxyisobutyric acid (PCIB), an
      antiauxin, was added to the cell culture before 2,4-D, it inhibited 2,4-D
      stimulated scopoletin uptake. This result suggests that the stimulation of
      scopoletin uptake was one of the auxin effects on tobacco cells. Among other
      classes of plant hormones that were tested, only salicylic acid stimulated the
      uptake. When these hormones were added to the cell cultures before 2,4-D, methyl
      jasmonate and kinetin reduced scopoletin uptake. These results suggest that this
      scopoletin uptake by tobacco cells is regulated by the interaction between
      different plant hormones.

PMID- 11297788
TI  - Kernel-specific cDNA clones encoding three different isoforms of seed storage
      protein glutelin from oil palm Elaeis guineensis.
AB  - The mRNA differential display method was used to identify and isolate cDNAs
      corresponding to transcripts that accumulate during the period of lipid
      synthesis, 12-20 weeks after anthesis (WAA) in the kernel of Elaeis guineensis,
      var. Tenera. We successfully isolated two cDNA clones, KT7 (312 bp) and KT8 (266
      bp). Interestingly, both clones show 79% nucleotide sequence identity to each
      other. This suggests that both clones encode the isoforms of the same protein. We
      screened the kernel (15 WAA) cDNA library and isolated the clone pKT7 (587 bp)
      using KT7 as probe, and isolated another isoform with KT8 probe, which designated
      as pKT9 (900 bp). Clone pKT9 has 93% nucleotide identity to KT8 and only 46% to
      pKT7 in their 3'-untranslated region. All three clones displayed significant
      amino acid sequence identity to seed storage protein glutelin from monocotyledon
      and globulin from dicotyledon plants. The coding sequence of KT8 (106 bp) shows
      76 and 97% identity to pKT9 and pKT7, respectively. Therefore, we suggest that
      clones KT8 and pKT7 are members of the same subfamily (A), while pKT9 belongs to
      another subfamily (B) of glutelin multigene families. Southern analysis shows
      that there are at least four members for the subfamily B. Northern analysis shows
      that these three members of the glutelin family are co-ordinately expressed and
      developmentally regulated during the development of the kernel. The transcripts
      begin to accumulate at 12 WAA, increase in 15 WAA and show a significant
      reduction at 17 WAA.

PMID- 11297789
TI  - The defense response elicited by the pathogen Rhizoctonia solani is suppressed by
      colonization of the AM-fungus Glomus intraradices.
AB  - Defense responses of alfalfa roots to the pathogenic fungus Rhizoctonia solani
      were reduced significantly in roots simultaneously infected with the vesicular
      arbuscular mycorrhizal (AM) fungus Glomus intraradices. R. solani induced five-
      to tenfold increases in the steady-state levels of chalcone isomerase and
      isoflavone reductase mRNAs a doubling of root peroxidase activity and a marked
      autofluorescence in the infected tissue. These changes were inhibited by the
      presence of G. intraradices. Interestingly, germination of G. intraradices spores
      and hyphal elongation were sensitive to low concentrations (2 uM) of medicarpin-3
      O-glucoside, an isoflavonoid phytoalexin that accumulated both in roots colonized
      by the pathogenic fungus as well as in AM-treated roots receiving high P, where
      no colonization by the beneficial fungus occurred. These data support the
      hypothesis that during early stages of colonization by G. intraradices,
      suppression of defense-related properties is associated with the successful
      establishment of AM symbiosis.

PMID- 11297790
TI  - An electron probe X-ray microanalysis study during organogenesis from internode
      derived nodules of Humulus lupulus var. Nugget.
AB  - Elemental changes during the induction of organogenesis from internode-derived
      nodules of Humulus lupulus var. Nugget were studied by electron probe X-ray
      microanalysis (EPMA) of specimens submitted to physical fixation procedures. X
      ray spectra were collected from cambial and cortical cells. Four days after
      explants inoculation an increase of K and Ca was detected in cells of both
      regions. Four to twelve days after explants inoculation an increase of Cu, Zn,
      Fe, S and Mn was therein detected. Values of Cu, Zn, Fe, K and S were lower in
      control explants than in induced explants 12 days after induction. Although S
      presented fluctuations it increased throughout the induction period. X-ray
      spectra collected from organogenic nodules revealed higher levels of Ca, K, Fe, P
      and S on peripheral regions where regeneration was occurring. Ca was mobilized in
      several directions, from inner regions of nodules towards their periphery at the
      onset of plantlet regeneration. Levels of Mg and Na were low or absent. Control
      explants neither formed nodules nor regenerated plantlets. The results suggest
      that EPMA can be used to study relative elemental changes during plant
      morphogenesis induction and enables the early establishment of organogenic
      regions in nodules.

PMID- 11297791
TI  - Glutathione reductase activity and chilling tolerance are induced by a
      hydroxylamine derivative BRX-156 in maize and soybean.
AB  - The possible contribution of antioxidants in the improvement of stress tolerance
      induced by the hydroxylamine derivative BRX-156 was studied in two thermophilic
      crops, soybean (Glycine max (L.) Merr.) and maize (Zea mays L.) both during
      germination and at the seedling stage. The most effective concentration of BRX
      156 for an increase in stress tolerance was determined by the complex stressing
      vigour test (CSVT), in which seeds were germinated under simultaneous anoxia and
      chilling (5 degrees C) stresses. Under CSVT conditions the activity of
      glutathione reductase (GR, EC 1.6.4.2), was increased by BRX-156 by up to 200 and
      150% in soybean and maize, respectively. Treatment with BRX-156 only resulted in
      a significantly greater activity of glutathione S-transferase (GST, EC 2.5.1.18)
      in maize. When young seedlings were chilled at 5 degrees C for a week, the
      increase in recovery induced by BRX-156 was accompanied by increased GR activity.
      The GSH synthesis was not affected by BRX-156 under these conditions. Induction
      of GR activity contributes to the improvement of abiotic stress tolerance by BRX
      156 in maize and soybean.

PMID- 11297792
TI  - Differential induction of Orobanche seed germination by Arabidopsis thaliana.
AB  - Parasitic plants, including the root holoparasites Orobanche spp., cause
      devastating damage to crops worldwide. Arabidopsis thaliana (L.) is widely used
      an amenable model for the study of plant biology, including plant-pathogen
      interactions. Bringing the two plants together in a controlled system will enable
      the study of the molecular and genetic basis involved in host-parasitic plant
      interactions and should provide tools for the detection of genes responsible for
      incompatibility and resistance responses. The objective of this study was to
      screen Arabidopsis lines for reduced germination of Orobanche seeds. A 96-cell
      well bioassay was developed to test the potential of lines, ecotypes and mutants
      of Arabidopsis to induce germination of Orobanche. Screening of 50 A. thaliana
      ecotypes did not reveal non-inducing ecotypes. Screening of 13000 A. thaliana
      fast neutron mutated M2 plants detected 94 non-inducing mutant plants of which 34
      were rescued, self pollinated, and M3 seeds collected. M3 seedlings from five
      lines were reduced in their ability to induce germination. In a separate assay,
      we determined that the reduced germination rates corresponded with reduced
      distance from the roots at which germination occurred. While further studies are
      necessary to determine the segregation of low germination phenotypes, these lines
      might prove useful for studying the genetic basis of variation in germination
      stimulant production in A. thaliana.

PMID- 11297793
TI  - Molecular cloning, characterization and expression analysis of a catalase cDNA
      from hot pepper (Capsicum annuum L.).
AB  - We report the cloning of a catalase cDNA from hot pepper (Capsicum annuum L.) and
      its expression patterns. CaCat1 is consisted of 1837 bp containing one open
      reading frame (ORF) of 1479 and 45 bp/313 bp of 5'/3'-untranslated region.
      Deduced amino acid sequence of CaCat1 showed the 95% and 78% identity with that
      of Nicotiana tabacum Cat1 and Nicotiana plumbaginifolia Cat2, respectively.
      Northern hybridization shows that CaCat1 transcripts are more abundant in stems
      than in leaves and roots, and in early stages than in mature stage of fruit
      development. In roots its transcripts are induced in response to aluminum and
      NaCl. In addition, its transcription levels under light (12 h)/dark (12 h) cycle
      and constant light conditions exhibit circadian rhythm, reaching a maximum at
      late in the dark period or early in the light period. The morning specific
      circadian regulation of CaCat1 was also observed in NpCat1, but not in NtCat1,
      suggesting difference in evolutionary rates between coding region and regulatory
      region of the catalase genes.

PMID- 11297794
TI  - Terpenoid indole alkaloid profile changes in Catharanthus pusillus during
      development.
AB  - The terpenoid indole alkaloid content of Catharanthus pusillus was investigated
      during development from young to old plants. Different plant organs were assessed
      showing that the new leaves were the main repository site with vindoline (
      approximately 4.8 mg/g DW) and catharanthine ( approximately 2.2 mg/g DW) being
      the major metabolites with the highest yields at the second and third sampling
      time (51 and 70 days, respectively). The other samples analysed, from old, oldest
      and yellow leaves followed in accumulation levels. The roots and stems were the
      least accumulative organs, although for the case of tubotaiwine the root was the
      most important organ. It appeared that the alkaloid content changed coinciding
      with the different developmental stages of the plants, particularly at flowering
      and fruiting stages. Moreover, this species seems to constitute a precious source
      of the monomerics, vindoline and catharanthine, intermediates in the synthesis of
      the two important antitumor dimerics vincristine and vinblastine, which did not
      accumulate in this species.

PMID- 11297795
TI  - Characterization of a soybean
AB  - Kunitz trypsin inhibitor, an abundant soybean [Glycine max (L.) Merr.] seed
      protein, has a molecular mass of 21500 Da and is specific for serine proteases. A
      soybean mutant (P.I. 196168) was characterized to determine the molecular basis
      for reduced Kunitz trypsin inhibitor levels during seed development. Western blot
      analysis revealed that P.I. 196168, in comparison to Amsoy 71, accumulated low
      amounts of Kunitz trypsin inhibitor protein. Non-denaturing polyacrylamide enzyme
      activity gels indicated that Amsoy 71 seeds contained at least five distinct
      zones of trypsin inhibitor activity. However, P.I. 196168 contained only four
      zones of enzyme inhibition. The coding region of the most abundant trypsin
      inhibitor gene (KTi3) was isolated from Amsoy 71 and P.I. 196168 by PCR. DNA
      sequence comparisons of the Kunitz trypsin inhibitor coding regions revealed two
      deletions and one G to T transversion have occurred. These mutations introduced
      four stop codons in the reading frame, resulting in a truncated protein. Northern
      blot analysis revealed that P.I. 196168 accumulated drastically lower amounts of
      KTi3 mRNA when compared with Amsoy 71.

PMID- 11297796
TI  - Immunocytochemical studies on the origin and deposition sites of hydrolyzable
      tannins.
AB  - Two specific antibodies, directed toward hydrolyzable tannins, i.e.
      polygalloylated or oxidized derivatives of 1,2,3,4,6-penta-O-galloylglucose, and
      toward an acyltransferase from oak leaves that catalyzes the biosynthesis of this
      principal precursor, were used in immunocytochemical studies to determine the
      intracellular sites of origin and deposition of these polyphenolic plant
      constituents. Immunostaining of semi-thin sections from leaves and roots of young
      pedunculate oak (Quercus robur, syn. Quercus pedunculata) plants with marker
      enzymes and immunogold labeling of ultra-thin sections revealed immunoreactive
      sites for both enzyme and hydrolyzable tannins in chloroplasts, cell walls and
      intercellular spaces. The latter non-cytoplasmic (apoplast) compartments
      displayed characteristic aggregations of these two epitopes, thus indicating an
      intimate association of the biocatalyst and its products. Identical distribution
      patterns for hydrolyzable tannins were observed in leaves of Rhus typhina (sumac)
      and Tellima grandiflora (fringe cups) which, however, displayed no affinity
      toward the galloyltransferase antibody that had been raised against enzyme from
      oak. Controls with spinach leaves, known to be devoid of tannins, were inactive
      in all cases. The conclusion that, besides chloroplasts, cell walls and
      intercellular space serve as sites for the biosynthesis and deposition of
      hydrolyzable tannins was confirmed by analyzing extracts from these non
      cytoplasmic compartments.

PMID- 11297797
TI  - Molecular cloning and functional analysis of pea cDNA E86 encoding homologous
      protein to hypersensitivity-related hsr203J.
AB  - Clone E86 was isolated as cDNA for elicitor-inducible gene from pea epicotyls by
      differential screening. The deduced amino acid sequence of E86 showed high
      homology to hypersensitivity-related protein hsr203J in tobacco and also showed
      significant homologies to the Ser-active hydrolases, such as mammalian hormone
      sensitive lipases, bacterial lipases and esterases. E86 polypeptide possesses
      consensus amino acid sequence motifs (His-Gly) and (Gly-X-Ser-X-Gly) conserved in
      lipases and esterases and showed esterase degradation of p-nitrophenyl butyrate.
      Northern blot analysis revealed that the E86-transcript is abundant in roots and
      stems and was induced by fungal elicitor in pea epicotyls. However, elicitor
      induced accumulation of E86 mRNA was significantly inhibited by the fungal
      suppressor. Furthermore the expression of the genes encoding E86 and
      phenylalanine ammonia-lyase was induced within 1 h after the inoculation of a
      nonpathogen, but it was delayed for 5 h by the inoculation of a compatible
      pathogen. These results suggest that the elicitor-induced Ser-active hydrolase
      derived from E86 gene might be related to the plant defense responses.

PMID- 11297798
TI  - Hydropassive evidence and effective factors in stomatal oscillations of
      Glycyrrhiza inflata under desert conditions.
AB  - Whether stomata oscillations induced by atmospheric drought stress are
      hydropassive or metabolic energy-dependent and the thresholds of some effective
      factors were studied in Glycyrrhiza inflata. The metabolic inhibitors NaN(3) and
      carbonyl cyanide-m-phenyl-hydrazone inhibited the respiration. However they could
      not significantly change the intensity (amplitude/average) of the stomata
      oscillation. The leaf turgor-pressure was fluctuated simultaneously with the
      stomata oscillations, whereas the K(+) content of the guard cells did not show
      oscillations. The oscillation intensity was found to be regulated by vapour
      pressure deficit (VPD), the proportion of the retained root and the stem flux
      lag. The minimum threshold of VPD, roots and the stem flux lag may be required to
      induce the stomata oscillations. The fluctuations of the leaf turgor-pressure
      induced by the non-synchronization between the transpiration demand and provide
      of water by the stem flux may be the direct cause of the stomata oscillations in
      G. inflata under the conditions of high transpiration demand.

PMID- 11297799
TI  - A cost effective protocol for in vitro mass propagation of cauliflower.
AB  - An improved and cost effective protocol for in vitro mass propagation of
      cauliflower from fractionated and graded curd is presented. The protocol is
      optimised for the production of clones of 2000 plants from one mother curd.
      Microshoots are produced en masse in 12 days, selected by flotation on a sucrose
      pad and transferred to rooting medium after suspension in a viscous medium. Fully
      rooted propagules are transferred to the glasshouse in 4-5 weeks and ready for
      transfer to the field 3-5 weeks later. The propagule unit cost was drastically
      reduced and is now close to that of a seed derived module grown plantlet. The
      strengths and limitations of this protocol are discussed. Clones produced highly
      homogeneous curds in the field with a short cutting period. Their overall quality
      depended essentially on the quality of the selected mother curd. The screening of
      populations to select elite genotypes combining high quality curd and good
      response in vitro is central to the use of this protocol on an industrial scale.

PMID- 11297800
TI  - The lectin from the mushroom Pleurotus ostreatus: a phosphatase-activating
      protein that is closely associated with an alpha-galactosidase activity. A part
      of this paper has been presented as a preliminary report at the 17th Interlec.
      Meeting 1997 in Wurzburg, Germany.
AB  - The lectin from the mushroom Pleurotus ostreatus described earlier [F. Conrad, H.
      Rudiger, The lectin from Pleurotus ostreatus: purification, characterization and
      interaction with a phosphatase, Phytochemistry 36 (1994) 277-283] was further
      characterized. Determination of the isoelectric point by capillary
      electrophoresis gave a value of 7.6. The dissociation constant of the lectin
      alpha-lactose-1-phosphate complex determined by capillary electrophoresis is 3
      mM. The activation of an endogenous phosphatase by the lectin as found earlier
      for the pseudosubstrate p-nitrophenylphosphate was confirmed also for naturally
      occurring substrates as ADP and ATP. We observed that at all purification steps
      the lectin is accompanied by an alpha-galactosidase activity. Both activities
      could neither be resolved by electrophoresis under non-denaturing conditions nor
      by affinity chromatography. However, carbohydrate binding by the lectin and
      carbohydrate processing by the enzyme are not due to the same site since: (i) the
      lectin accepts both alpha- and beta-glycosides whereas the enzyme activity is
      restricted to the alpha-anomer; (ii) the interaction with erythrocytes leads to a
      stable agglutinate, i.e. no 'clot-dissolving activity' [C.N. Hankins, J.I.
      Kindinger, L.M. Shannon, Legume alpha-galactosidases which have hemagglutinin
      properties, Plant Physiol. 65 (1980) 618-622] is observed; (iii) the alpha
      galactosidase activity is inhibited by galactose but not by a beta-galactoside.
      Therefore, lectin and enzymatic activities are either properties of two tightly
      associated proteins, or of just one molecule. The kinetic parameters of the
      lectin-associated alpha-galactosidase activity for p-nitrophenyl-alpha
      galactopyranoside are: K(M)=2.5 mM, k(cat)=66 s(-1), and K(I)=20mM for the
      inhibitor D-galactose.

PMID- 11297802
TI  - Calystegines in root cultures of Atropa belladonna respond to sucrose, not to
      elicitation.
AB  - Calystegines are norpseudotropine alkaloids accumulating in root cultures of
      Atropa belladonna, together with tropine derivatives, e.g. hyoscyamine. Both
      alkaloid groups are derived from the tropane alkaloid pathway. For the
      investigation of the regulation and individual steps of tropane biosynthesis,
      methods for the induction of the pathway were tested. Elicitation by chitosan, or
      defence responses to ABA and methyl jasmonate did not enhance calystegine
      accumulation, but led to a more or less pronounced decrease. By blocking one arm
      of the diverged tropane pathway, calystegine accumulation can be increased, but
      total tropane alkaloid formation does not increase considerably. By elevation of
      sucrose supply, both, total alkaloids and calystegines in particular were
      increased approximately threefold. The mechanism of the induction of the
      biosynthesis by sucrose is not known and needs further experiments.

PMID- 11297801
TI  - Transgenic rice plants expressing the ferredoxin-like protein (AP1) from sweet
      pepper show enhanced resistance to Xanthomonas oryzae pv. oryzae.
AB  - We used particle bombardment to cotransform mature seed-derived rice callus
      (Oryza sativa L., ssp. japonica, cv. Eyi 105) with plasmids containing the linked
      marker genes gusA and hpt, and the ap1 gene encoding an amphipathic protein
      previously shown to delay the hypersensitive response induced in non-host plants
      by the pathogen Pseudomonas syringae pv. syringae (Pss). Thirty-two independent
      lines of transgenic rice plants were regenerated, and 27 of these lines carried
      all three transgenes as shown by molecular analysis. A bacterial blight
      inoculation test was carried out on ten lines. In each case, plants carrying the
      ap1 gene showed enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo) race 6
      at various levels. This suggests the ap1 gene could be a useful candidate for
      genetic engineering strategies in rice to provide bacterial blight resistance.

PMID- 11297803
TI  - Cytokinin-like activity of N,N'-diphenylureas. N,N'-bis-(2,3
      methylenedioxyphenyl)urea and N,N'-bis-(3,4-methylenedioxyphenyl)urea enhance
      adventitious root formation in apple rootstock M26 (Malus pumila Mill.).
AB  - Vegetative propagation of cuttings is a widespread method to multiplicate plants.
      Adventitious root formation is a key step in vegetative propagation and
      considerable progress has recently been made in understanding root formation.
      But, in spite of the efforts made, no new rooting treatments have been developed.
      Here, we report for the first time, that N,N'-bis-(2,3-methylenedioxyphenyl)urea
      and N,N'-bis-(3,4-methylenedioxyphenyl)urea enhance adventitious root formation
      in microcuttings of Malus pumila Mill. rootstock M26. Roots emerge without auxin
      supplementation in the darkness, transfer in hormone free medium, or callus
      formation. With the use of different bioassays, we also demonstrate that these
      two diphenylurea derivatives do not show cytokinin- or auxin-like activity.

PMID- 11297804
TI  - Rat model of lung fibrosis: comparison of functional, biochemical, and
      histopathological changes 4 months after single irradiation of the right
      hemithorax.
AB  - This study investigated changes in lung function, hydroxyproline (OH-pro) content
      of lung tissue and histopathology in anesthetized, spontaneously breathing rats
      after a single, selective irradiation of the right hemithorax with a single dose
      of 20 Gy. The objective of this animal model was to examine as to whether non
      invasive lung function measurements (LFM) could be used to analyze the magnitude
      of the irradiation-related pneumonitis and its long-term sequel occurring in the
      right lung in the presence of a normal left lung. Four months after irradiation,
      the OH-pro content in the irradiated right lung was determined and compared with
      the non-irradiated contralateral left lung, as well as lungs from non-irradiated
      sham controls. LFM revealed significantly depressed flow-volume curves and
      reduced quasistatic compliance, suggesting a marked diminution of elastic recoil
      of the lung. Total lung capacity (TLC) was significantly decreased, while the
      residual volume (RV) and functional residual capacity (FRC) remained almost
      unchanged. One of the most predominant dysfunction of the lung was a severe
      maldistribution of ventilation shown by the single-breath N(2)-wash-out test.
      Single-breath carbon monoxide diffusing capacity (Dlco) was significantly
      decreased. The content of OH-pro, a marker of increased collagen, was
      significantly increased in the irradiated right lung but was indistinguishable
      from sham controls in the non-irradiated left lung. Histopathological
      examinations provided evidence of both inflammatory and fibrotic lesions in the
      irradiated lobes, including bronchiolo-alveolar hyperplasia. No changes were
      observed in the non-irradiated left lung. In summary, effects observed in the
      irradiated right lung were largely consistent with effects described in other
      animal models of human interstitial pulmonary fibrosis. Non-invasive LFM were
      considered to be particularly sensitive to study the overall extent of changes,
      however, the interpretation of findings appears to be complicated by the lobar
      heterogeneity of tissue- and flow-related functional end points.

PMID- 11297805
TI  - The metabolism and bioactivation of agaritine and of other mushroom hydrazines by
      whole mushroom homogenate and by mushroom tyrosinase.
AB  - Whole homogenates of Agaricus bisporus metabolised the mushroom hydrazine
      agaritine [beta-N-(gamma-L(+)glutamyl)-4-(hydroxymethyl) phenylhydrazine] to
      generate at least three metabolites. None of these metabolites, however, was the
      free hydrazine [4-(hydroxymethyl)phenylhydrazine], the postulated metabolite of
      agaritine believed to be formed as a result of the loss of the gamma-glutamyl
      group, the reaction being catalysed by gamma-glutamyltransferase. The three
      metabolites of agaritine displayed weak mutagenic activity towards Salmonella
      typhimurium strain TA104. 4-(Hydroxymethyl)phenylhydrazine, as the N'-acetyl
      derivative, was metabolised by mushroom tyrosinase to yield a number of
      metabolites that induced a mutagenic response in S. typhimurium TA104. Similar to
      N'-acetyl-4-(hydroxymethyl)phenylhydrazine, agaritine was extensively metabolised
      by the mushroom tyrosinase but, in contrast, the structurally related N'-acetyl-4
      hydrazinobenzoic acid did not serve as substrate of this enzyme, implying a
      critical role for the hydroxymethyl group at the para-position. In conclusion,
      the current studies have demonstrated for the first time that: (a) whole mushroom
      homogenates readily metabolise agaritine but not to the postulated 4
      (hydroxymethyl)phenylhydrazine; and (b) mushroom tyrosinase metabolises agaritine
      and N'-acetyl-4-(hydroxymethyl)phenylhydrazine, in the latter case forming
      genotoxic metabolites.

PMID- 11297806
TI  - Cytotoxicity effects of di- and tri-hydroxybenzaldehydes as a chemopreventive
      potential agent on tumor cells.
AB  - As part of our earlier search for new compounds with improved biological
      activities including antioxidant, anti-inflammatory, and tumor growth inhibition
      activities, we synthesized 2,4,5-trihydroxybenzaldehyde (2,4,5-THBA) from
      commercially available Sesamol. First we examined the free radical-quenching
      capacity of 2,4,5-THBA, 3,4-dihydroxybenzaldehyde (3,4-DHBA), and 2,5
      dihydroxybenzaldehyde (2,5-DHBA) in vitro by 1,1-diphenyl-1,2
      picryhydrazylradical (DPPH) test. The antioxidant bioactivity was also evaluated
      using the model of t-butyl hydroperoxide (t-BHP)-induced cytotoxicity in rat
      primary hepatocytes. Finally, three chemicals were tested by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay on human
      nasopharynx carcinoma cells (KB cells), human hepatoblastoma (HepG2), and human
      leukemia HL-60 cells. The 2,4,5-THBA shows significant cytotoxicity on HL-60
      cells. The results suggest that 2,4,5-THBA may be a potential chemopreventor or
      chemotherapy agent against HL-60 cells.

PMID- 11297807
TI  - Histopathological alterations in the brain regions of rats after perinatal
      combined treatment with cadmium and dexamethasone.
AB  - Industrial and environmental exposure to cadmium (Cd) is well known to produce
      multiorgan toxicity in humans. Metallothionein (MT) is a cellular ligand for Cd.
      MT has been shown to protect against Cd-induced toxicity in many organs,
      including brain. In this study, we described the histopathological alterations in
      parietal cortex, striatum, hippocampus and cerebellum of rats following perinatal
      combined exposure to cadmium and dexamethasone (Dx), a drug known to induce MT
      synthesis in brain. Wistar rats of 13 days of age were treated for 5 days, as
      follows; (1) saline solution, (2) CdCl(2) 1 mg/kg per day, (3) Dx 2 mg/kg per
      day, (4) CdCl(2) 1 mg/kg per day + Dx 2 mg/kg/day. Rats were killed on either 18
      or 28 days of age. The content of Cd in parietal cortex, striatum, hippocampus
      and cerebellum at 18 days old age increased 58.3-, 9.4-, 18.3- and 11.3-fold,
      while at 28 days of age in the same regions the increases were 6.6-, 5.8-, 25.3-
      and 11.3-fold in the Cd treated rats, respectively. No lesions were observed in
      the brain of control rats. Rats treated with Dx at 28 days of age showed
      interstitial edema in the four regions. Cd-treated rats at 28 days of age showed
      lesions in the four studied regions. In general, Dx treatment attenuated all Cd
      induced lesions.

PMID- 11297808
TI  - Effects of in vivo exposure of Mya arenaria to organic and inorganic mercury on
      phagocytic activity of hemocytes.
AB  - Marine bivalves are aquatic invertebrate organisms which can be used as
      bioindicators in environmental monitoring. In vivo effects of mercuric chloride
      (HgCl(2)) and methylmercury (CH(3)HgCl) on phagocytic function of Mya arenaria
      hemocytes were evaluated in this study. Clams were exposed to single metal in
      water for up to 28 days at concentrations ranging from 10(-9) to 10(-5) M.
      Phagocytic activity of hemocytes was determined by uptake of fluorescent
      microspheres and flow cytometry. All clams exposed to 10(-5) M HgCl(2) died by
      day 7 of exposure. The viability of hemocytes was decreased only in clams exposed
      to 10(-6) M HgCl(2) for 28 days. A significant decrease in phagocytic activity of
      hemocytes was observed in clams exposed to 10(-6) M of HgCl(2) for 28 days. A
      similar pattern was observed with CH(3)HgCl, but at an earlier time. Chemical
      analysis performed on the tissues of the animals clearly show a greater uptake of
      the organic form of mercury by clams. Furthermore, a clear correlation was
      established between body burden of mercury and effects on phagocytic activity of
      hemocytes. Overall, the results of this study show that both speciations of
      mercury inhibited phagocytic function of Mya arenaria hemocytes following in vivo
      exposures.

PMID- 11297809
TI  - Firing properties of identified superior laryngeal neurons in the nucleus
      ambiguus in the rat.
AB  - Superior laryngeal motoneurons control muscles in the larynx and recent work has
      shown they also have axon collaterals that project to cardiac vagal neurons in
      the nucleus ambiguus. The present study was undertaken to identify and examine
      the firing properties of superior laryngeal neurons (SLNs) in the rat. SLNs
      typically fired spontaneously and repetitively at a rate of 4-7 Hz. The firing
      was continuous and showed little bursting activity. Firing evoked
      afterhyperpolarizations were insensitive to apamin but blocked by charybdotoxin.
      The voltage-gated currents in SLNs consist of a TTX-sensitive Na current and a 4
      aminopyridine sensitive K current. It is likely that the activity of these
      neurons not only control respiratory laryngeal muscles, but may also provide an
      interaction between the respiratory system and the control of the heart rate.

PMID- 11297810
TI  - The horizontal vestibulo-ocular reflex of hypergravity rat at different gravity
      levels.
AB  - The horizontal vestibulo-ocular reflex (VOR) of two groups of rats was measured.
      One group was bred and kept under hypergravity (HG; 2.5 g) conditions, the other
      group lived under normal gravity (NG; 1 g). Eye position was recorded in response
      to horizontal rotatory stimuli. Measurements were made under NG (1 g), and during
      parabolic flight (0.0 and 1.8 g). For both groups, the response to a rotatory
      stimulus during parabolic flight is similar to the response that was observed
      under 1 g conditions. In general, however, the VOR of HG rats is reduced by 20
      50% relative to the response of NG rats and the phase is shifted by -40 degrees.
      We conjecture that this amplitude reduction and phase shift are the consequence
      of living in a rotating system.

PMID- 11297811
TI  - D(3) dopamine receptors in rat spinal cord: implications for sensory and motor
      function.
AB  - Quantitative autoradiography was used to determine the distribution of D(3)
      receptors in rat spinal cord and compare it with the distribution of D(1)-like
      and D(2) (and D(4)) receptors. [(3)H]PD 128907-labeled D(3) sites were observed
      in roughly 6-fold lower density than [(3)H]spiperone-labeled D(2) (D(4)) sites
      and 60-fold lower density than [(3)H]SCH 23390-labeled D(1)-like sites. Highest
      densities of D(3) binding were observed in the superficial layers of the dorsal
      horn at cervical and lumbar levels followed by the pars centralis and dorsal
      horn. Lowest densities of D(3) sites were detected in the ventral horn. These
      observations suggest that spinal D(3) receptors may play a role in sensory and/or
      motor function or contribute to the pharmacological effects of dopaminergic
      drugs.

PMID- 11297812
TI  - Toosendanin-induced inhibition of small-conductance calcium-activated potassium
      channels in CA1 pyramidal neurons of rat hippocampus.
AB  - The effect of toosendanin (TSN) on small-conductance calcium-activated potassium
      channels (SK(Ca)) in pyramidal neurons of rat hippocampal CA1 region was observed
      using the inside-out configuration of patch-clamp technique. The results showed
      that TSN (1.7 approximately 170 microM) inhibited the SK(Ca) activity by reducing
      the open probability and open frequency significantly in a concentration
      dependent manner, and the effects were partially reversible. Elevating Ca2+
      concentration at the intracellular side of the patch ([Ca2+](i)) from 1 to 10
      microM decreased the inhibitory efficacy. Analysis of the channel kinetics
      indicated that TSN increased the slow closed time constant significantly, while
      open time and unitary conductance of channel did not change. These data provide a
      further explanation for TSN-induced facilitation of neurotransmitter release and
      antibotulismic effects of the drug.

PMID- 11297813
TI  - The neurotensin antagonist SR 48692 attenuates haloperidol-induced striatal Fos
      expression in the rat.
AB  - Neurotensin interacts with central dopamine systems and has been suggested to
      exert antipsychotic drug-like actions. Antipsychotic drugs such as haloperidol
      induce striatal immediate-early gene expression. In order to study neurotensin's
      role in antipsychotic drug actions, rats were pretreated with the neurotensin
      antagonist SR 48692 and then injected with haloperidol. SR 48692 dose-dependently
      decreased haloperidol-elicited immediate-early gene expression in the
      dorsolateral and central striatum but not other striatal areas. SR 48692 reduced
      Fos expression in the striatal patch (striosome) and matrix compartments, with a
      significantly greater effect in the patch. These data suggest that neurotensin
      may play a role in the actions of haloperidol. In view of proposed functional
      roles of the striatal patch and matrix, we suggest that neurotensin may be
      important in the therapeutic rather than side effects of antipsychotic drugs.

PMID- 11297814
TI  - cAMP and calcium ionophore induce outgrowth of neuronal processes in PC12 mutant
      cells in which nerve growth factor-induced outgrowth of neuronal processes is
      impaired.
AB  - During continuous culturing, PC12 cells are subject to spontaneous mutations. We
      obtained PC12m3 cells, clone cells in which outgrowth of neuronal processes
      (dendrites and axons) under the condition of nerve growth factor (NGF) treatment
      was highly stimulated by various inducers, such as cyclic adenosine monophosphate
      (cAMP), calcium ionophore, steroid and high osmolarity. The number of cells with
      neuronal processes in the presence of cAMP was approximately twenty-fold greater
      than PC12 parental cells and other PC12 mutant cells. In PC12m3 cells, NGF
      induced outgrowth of neuronal processes was reduced by cytotoxic solanine,
      whereas the effect of NGF was unaffected by hyaluronic acid. In PC12m3 cells,
      various inducers of neurite outgrowth, such as cAMP, calcium ionophore and high
      osmolarity, activated mitogen activated protein (MAP) kinase, whereas solanine
      and hyaluronic acid did not cause any significant activation of MAP kinase.
      However, PC12m3 cells, in which NGF-induced outgrowth of neuronal processes were
      impaired, had strong NGF-induced MAP kinase activity as PC12 parental cells had.
      These findings suggest that cAMP, calcium influx and high osmolarity induce
      outgrowth of neuronal processes in PC12m3 cells through activation of the
      downstream target of MAP kinase or through a novel pathway independent of NGF
      activation.

PMID- 11297815
TI  - Expression of tachykinin NK2 receptor mRNA in human brain.
AB  - Tachykinin NK2 receptors have been suggested to play an important role in the
      central nervous system. This study, using reverse transcription-polymerase chain
      reaction revealed a detectable expression of NK2 receptor mRNA in various human
      brain regions, including the caudate nucleus, the putamen, the hippocampus, the
      substantia nigra and the cerebral cortex. The distribution of NK2 receptor
      expression in the cortex revealed a major expression in frontal and temporal
      cortex compared to occipital and parietal areas. These results provide a
      molecular basis for considering a role of NK2 receptors in human pathophysiology.

PMID- 11297816
TI  - N-methyl-D-aspartate receptors and information processing: human choice reaction
      time under a subanaesthetic dose of ketamine.
AB  - Ketamine is an N-methyl-D-aspartate antagonist that induces cognitive
      dysfunctions. The purpose of the present study was to investigate the effects of
      a subanesthetic dose of ketamine on human information processing, using the
      additive factor method. During perfusion of a subanesthetic dose of ketamine (0.5
      mg/kg over 60 min) or a placebo (randomized double-blind, cross-over design),
      eight adults (aged 22-33, mean=27) performed a two-choice visual reaction time
      (RT) task. Signal intensity, stimulus-response mapping, and foreperiod duration
      were manipulated. The effects of these three variables were found to be additive
      on RT, indicating that three independent stages - namely, stimulus preprocessing,
      response selection and motor selection- were manipulated. Ketamine altered RT
      performance in a specific way: it interacted with foreperiod duration but its
      effect was additive with those of signal intensity and stimulus-response mapping.
      These results show that ketamine specifically affects the stage of motor
      adjustment, which suggests that the glutamatergic system plays an important role
      in motor processes.

PMID- 11297817
TI  - Nitric oxide synthase gene polymorphisms in Alzheimer's disease and dementia with
      Lewy bodies.
AB  - Evidence suggests that vascular and inflammatory components may be important in
      the aetiology of dementia and genetic risk factors affecting these processes may
      therefore influence disease development. Recently, polymorphisms in the
      endothelial constitutive nitric oxide synthase 3 (NOS3) and also the inducible
      nitric oxide synthase gene (NOS2A) have been suggested to lead to increased risk
      of Alzheimer's disease (AD) or dementia with Lewy bodies. We have studied the
      relationship of both these NOS gene polymorphisms to development of AD and
      dementia with Lewy bodies and find no evidence for association with either
      condition. We conclude that NOS gene polymorphisms do not alter disease risk in
      the majority of late-onset dementia cases.

PMID- 11297818
TI  - Nicotinic acetylcholine receptor subtypes in rat superior cervical ganglion
      neurons as studied by sequential application of two alpha-subunit-specific
      antibodies.
AB  - All cultured neurons of rat superior cervical ganglion (SCG) were stained with
      nicotinic acetylcholine receptor (nAChR) alpha5- or alpha7-subunit-specific
      oligoclonal antibodies (Abs) and could additionally bind alpha3-subunit-specific
      monoclonal antibody (mAb). About 60% of the neurons were stained with alpha4
      specific Ab and could not bind alpha3-specific mAb. The acetylcholine-induced
      membrane currents recorded with the whole-cell patch clamp method and partially
      blocked with alpha3-specific mAbs, could be additionally blocked with alpha5- and
      alpha7- specific Abs, and vice versa. The results suggest that: (1) each neuron
      of rat SCG expresses several nAChR subtypes with different alpha-subunits; (2)
      the alpha3-, alpha5- and alpha7-subunit-containing nAChRs are probably located
      far enough from each other thus enabling joint binding to the cell of the
      corresponding alpha-subunit specific Abs, in contrast to the alpha4-subunit
      containing nAChRs which are probably located too close to the alpha3-containing
      ones to allow their joint binding.

PMID- 11297819
TI  - Elastase is not required for L-DNase II activation during apoptosis in developing
      chicken neural retina.
AB  - During retinal development, the neuronal death is carried out by the mechanism of
      apoptosis. Among the different endonucleases activated, L-DNase II seems to be
      responsible for most of DNA degradation in this tissue. L-DNase II derives from
      LEI (Leukocyte Elastase Inhibitor) by a post-translational modification carried
      out by elastase in apoptosis induced in vitro. In this study, we investigated
      whether elastase could be implicated in apoptosis occurring during retinal
      development. Although elastase and LEI/elastase complex are colocalized in
      retinal sections, the LEI/elastase complex, detected by Western blot, does not
      change at all stages of development. However, at pH 4 retinal extracts show an
      enhanced activation of the L-DNase II. These results suggest that an acid
      protease, such as a cathepsin, may be implicated in neuronal retinal apoptosis.

PMID- 11297820
TI  - Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary
      cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout
      mice.
AB  - Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthine
      phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the
      etiology of which is still unclear. Evidence has accumulated indicating that it
      reflects dopamine deficiency associated with defective arborization of
      dopaminergic dendrites. We monitored the differentiation in vitro of dopaminergic
      neurons, cultured from HPRT-deficient knockout mice. The HPRT-deficient
      dopaminergic neurons exhibited a decelerated rate of outgrowth of dendrites in
      comparison to that of control neurons resulting, after 8 days in culture, in 32%
      smaller average total length of dendrites per neuron (P<0.025). The results
      suggest that the abnormal dendrite outgrowth in LNS reflects a defective
      developmental process.

PMID- 11297821
TI  - Two loci of the insular cortex project to the taste zone of the nucleus of the
      solitary tract in rats.
AB  - Distribution of insular cortical neurons projecting to the taste zone of the
      solitary tract nucleus (NTS) was examined histologically in rats. Injection of
      wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the taste
      responsive regions in the NTS resulted in labeling of cells in layer V within
      almost entire extent of the rostrocaudal axis of the granular and dysgranular
      areas of the insular cortex (IC) bilaterally with a clear contralateral
      dominance. The density of the cells was highest in the taste area of the IC [11]
      and second highest in the IC area around the bregma level, showing a bimodal
      distribution. After WGA-HRP injection into the IC taste area or the caudal IC,
      dense or sparse anterograde labeling was seen in the rostral NTS, respectively.
      The results indicate that not only the IC taste area but also the caudal IC
      exerts control influences directly upon the NTS taste zone.

PMID- 11297822
TI  - Oligosynaptic pathways possibly relaying visceral and/or gustatory information to
      the olfactory bulb in the hedgehog tenrec.
AB  - Using anterograde and retrograde transport of wheat germ agglutinin we showed
      that the parabrachial nucleus, known to receive second order visceral and
      gustatory afferents, might project directly to the anterior olfactory nucleus
      which is connected with the olfactory bulb (OfB). Only a small bulbar region is
      targeted directly by parabrachial fibers. This region is located immediately
      adjacent to the accessory OfB and may be closely related to, if not identical
      with the modified glomerular complex. To further substantiate the presence of
      true parabrachio-bulbar projections thyrosine hydroxylase immunohistochemistry
      was employed. The absence of immunoreactive neurons in the parabrachial nucleus
      and the different distribution patterns of immunoreactive fibers and axons
      labeled with wheat germ agglutinin conjugated to horseradish peroxidase in the
      target areas make it unlikely that catecholaminergic fibers were involved in the
      projections shown.

PMID- 11297823
TI  - Curcuminoids from Curcuma longa L. (Zingiberaceae) that protect PC12 rat
      pheochromocytoma and normal human umbilical vein endothelial cells from betaA(1
      42) insult.
AB  - beta-Amyloid (betaA) induced oxidative stress is a well-established pathway of
      neuronal cell death in Alzheimer's disease. From turmeric, Curcuma longa L.
      (Zingiberaceae), three curcuminoids, curcumin, demethoxycurcumin, and
      bisdemethoxycurcumin, were found to protect PC12 rat pheochromocytoma and normal
      human umbilical vein endothelial (HUVEC) cells from betaA(1-42) insult, as
      measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      reduction assay. ED(50) values of curcumin, demethoxycurcumin, and
      bisdemethoxycurcumin toward PC12 and HUVEC cells were 7.1+/-0.3, 4.7+/-0.1, 3.5+/
      0.2 microg/ml and 6.8+/-0.4, 4.2+/-0.3, and 3.0+/-0.3 microg/ml, respectively.
      These compounds were better antioxidants than alpha-tocopherol as determined by
      DPPH radical trapping experiment. alpha-Tocopherol did not protect the cells from
      betaA(1-42) insult even at>50 microg/ml concentration. The results suggest that
      these compounds may be protecting the cells from betaA(1-42) insult through
      antioxidant pathway.

PMID- 11297824
TI  - Remodelling of sensorimotor maps in paraplegia: a functional magnetic resonance
      imaging study after a surgical nerve transfer.
AB  - The adult mammalian brain has the capacity of reorganising its neural connections
      in response to lesions/modifications of the peripheral and central nervous
      system. We show in vivo, using functional magnetic resonance imaging (fMRI), that
      in paraplegics the lower-limb sensorimotor cortex is invaded by the arm
      representation. This functional reshaping appears to be reversible. Indeed,
      surgical transfer of the ulnar nerve to the ipsilateral quadriceps and hip
      muscles allowed their contraction in a paraplegic patient. During fMRI, these
      voluntary movements activated the hip and thigh representation in sensorimotor
      cortex. We suggest that the functional recovery of the lower-limb functional maps
      might have been driven by the restored somatosensory inputs from the reactivated
      periphery. The voluntary movements of the lower-limbs are regained through the
      're-awakening' of the corresponding sensorimotor cortex.

PMID- 11297826
TI  - A sequence of postural muscle excitations precedes and accompanies isometric ramp
      efforts performed while sitting in human subjects.
AB  - The purpose of this study was to explore how the muscles which control postural
      body segments are activated during bilateral isometric ramp pushes exerted with
      the upper limbs by seated subjects. The paradigm under study presents the
      advantage that the subject is in a quasi-static posture, and since upper limbs
      are stretched out, the dynamic phenomena, which might occur, can only originate
      from the rest of the body, which means from the postural chain. A dynamometer was
      used to measure the horizontal force, Fx, exerted on the bar, and a custom
      designed force-plate was used to measure global reaction forces (Rx) and
      displacement of the centre of pressure (Xp) along the antero-posterior axis.
      Electromyograms (EMGs) were picked up by bipolar surface electrodes from 14
      muscles crossing the lower limb, pelvis, trunk and upper limb joints. It was
      shown that transient push efforts require monotonous EMG increase in postural as
      well as in focal muscles. The EMG sequence starts with the postural muscles and
      ends with the focal ones. The postural EMG sequence is anticipatory. It is
      concluded that the EMG sequence is programmed according to the task parameters,
      and that its role is to counteract in advance the perturbing effect of the
      effort, in order to allow the effort to be performed efficiently. It is suggested
      that excitation between the postural muscles is distributed according to their
      biomechanical role in relation to the supports.

PMID- 11297825
TI  - Perineurium inflammation and altered connexin isoform expression in a rat model
      of diabetes related peripheral neuropathy.
AB  - Diabetes related peripheral neuropathy involves both somatic and autonomic nerves
      and leads to an array of debilitating abnormalities. Mechanisms may include
      decreased neuronal conductance, reactive oxygen species, and decreased
      performance of the perineurium blood-nerve barrier. Here we studied the
      perineurium characteristics of the dorsal penile nerve in a rat model of diabetes
      related peripheral neuropathy. Immunohistochemistry showed extensive and
      perineurial cell-specific nitric oxide synthase2 staining in diabetic animals as
      compared to age matched controls (P<0.05); however no apparent difference in
      immunostaining pattern was observed for 3-nitrotyrosine (a stable biomarker of
      peroxynitrite formation). Significant reductions in connexins 32 and 26 were seen
      in the diabetic perineurium with no detectable levels of connexin 43 in either
      control or diabetic dorsal nerve. These data provide new evidence of perineurial
      cell inflammatory responses and altered gap junction protein expression during
      diabetes related neuropathies and suggests that strategies to protect this cell
      type may have therapeutic value.

PMID- 11297827
TI  - GHB: a new and novel drug of abuse.
AB  - There has been increasing attention in the United States to problems of abuse of
      gamma-hydroxybutyrate (GHB), with some evidence for problems in other parts of
      the world as well. In vitro and animal research show that, while GHB shares some
      properties with abused central nervous system depressant drugs, it has unique
      aspects of its pharmacology as well, including actions at a specific neural
      receptor which probably mediates many of its effects. Abuse potential assessment
      of GHB using standard animal models has not yielded a picture of a highly
      abusable substance, but little human testing has yet been done. Very little
      systematic data exist on tolerance and dependence with GHB, but both have been
      seen in human users. Quantitative data on the prevalence of GHB abuse is
      incomplete, but various qualitative measures indicate that a mini-epidemic of
      abuse began in the late 1980s and continues to the present. GHB is often included
      with the group of 'club drugs', and can be used as an intoxicant. It also has
      been used as a growth promoter and sleep aid and has been implicated in cases of
      'date rape', usually in combination with alcohol. Undoubtedly the easy
      availability of GHB and some of its precursors has contributed to its popularity.
      Recent changes in the control status of GHB in the US may reduce its availability
      with as yet unknown consequences for the scope of the public health problem. Drug
      abuse experts need to familiarize themselves with GHB as possibly representing a
      new type of drug abuse problem with some unique properties.

PMID- 11297828
TI  - Morphine responses in humans: a retrospective analysis of sex differences.
AB  - There is increasing evidence that sex modulates the effects of opioid analgesics
      in nonhumans, but few studies have examined this issue in humans. Over the past
      seven years we have conducted several studies in which the subjective,
      psychomotor, and physiological effects of intravenous morphine were examined in
      healthy volunteers. In a retrospective analysis encompassing six studies, we re
      examined the effects of 10 mg/70 kg (iv) morphine in 57 males and 27 females.
      There were some differences in morphine's subjective effects as a function of
      sex. Females reported higher ratings of 'coasting (spaced out),' 'heavy or
      sluggish feeling' and 'dry mouth.' No differences in degree of psychomotor
      impairment or physiological effects (miosis and respiration rate) of morphine
      emerged between males and females. Future studies should focus on other doses of
      morphine and other opioid drugs, assess multiple behavioral and physiological
      endpoints, and look at different subsamples of humans (e.g. opioid abusers).

PMID- 11297829
TI  - Substance abuse, pathological gambling, and impulsiveness.
AB  - This study evaluated behavioral and self-report indices of impulsiveness in
      pathological gambling substance abusers (n=27), non-pathological gambling
      substance abusers (n=63), and non-pathological gambling/non-substance abusing
      controls (n=21). The Bechara card task measured preferences for decks of cards
      that ranged in magnitude and probability of delayed and immediate rewards and
      punishers. The Stanford Time Perception Inventory (STPI) assessed orientation to
      the future, the Zuckerman Sensation Seeking Scale evaluated sensation seeking,
      and the Eysenck and Barratt scales measured impulsivity. A Principal Components
      analysis revealed that these personality measures comprised three distinct
      measures of impulsivity: impulse control, novelty seeking and time orientation.
      Linear contrast analyses revealed that substance abuse and pathological gambling
      resulted in additive effects on the impulse control and time orientation factors,
      but not on the novelty-seeking scale. Performance on the card task did not
      correlate with any of the three factors derived from the personality scale
      scores, but the presence of both substance abuse and pathological gambling had an
      additive effect on preferences for decks containing greater immediate gains but
      resulting in large punishers and overall net losses. These results provide
      further evidence of an association among substance abuse, pathological gambling,
      and impulsivity.

PMID- 11297830
TI  - Behavioral effects of flunitrazepam: reinforcing and discriminative stimulus
      effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital
      dependent rats.
AB  - Flunitrazepam was evaluated in several procedures that have been used extensively
      to study the behavioral effects and abuse potential of positive GABA(A)
      modulators. One group of monkeys (n=3) responded to receive injections of
      methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated
      vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received
      diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of
      flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital
      treated rats was evaluated. Flunitrazepam maintained i.v. self-administration
      that was, on average, less than that maintained by methohexital and greater than
      that maintained by saline. In drug discrimination studies, flunitrazepam
      substituted for pentobarbital and for triazolam and failed to substitute for
      flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when
      flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs
      emerged when either pentobarbital or flunitrazepam treatment was terminated.
      Taken together with data from previous studies, these data suggest that the abuse
      liability of flunitrazepam is comparable to that of other benzodiazepines.

PMID- 11297831
TI  - Reliability and discriminant validity of the Type I/II and Type A/B alcoholic
      subtype classifications in untreated problem drinkers: a test of the Apollonian-
      Dionysian hypothesis.
AB  - The present study tested the hypothesis that there are two broad groups of
      problem drinkers: the Apollonian-Dionysian distinction. Apollonian drinkers are
      defined by a later onset of alcohol problems, a slower developmental course, and
      less problem severity. Dionysian drinkers are defined by more severe alcohol
      problems, an earlier onset, and worse prognosis. The discriminant validity and
      classification agreement of five operations of the Apollonian-Dionysian model
      were tested in a general population (n=8643) and community sample (n=664). A
      kappa-means cluster analysis supported the Apollonian-Dionysian distinction.
      Dionysian problem drinkers were more likely to be males, report greater alcohol
      consumption, more alcohol related antisocial behavior, have a current DSM-IV
      alcohol dependence diagnosis, and comorbid depression. Apollonian problem
      drinkers were more prevalent in the general population and reported less severe
      drinking problems. Classification agreement was stronger for subtype models that
      incorporate dimensions of alcohol use and/or the frequency of negative
      consequences. Babor's Type A-Type B model demonstrated the strongest reliability
      and consistency over time.

PMID- 11297832
TI  - Effectiveness of propranolol for cocaine dependence treatment may depend on
      cocaine withdrawal symptom severity.
AB  - Propranolol may reduce symptoms of autonomic arousal associated with early
      cocaine abstinence and improve treatment outcome. This trial was an 8-week,
      double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent
      subjects. The primary outcome measure was quantitative urinary benzoylecgonine
      levels. Secondary outcome measures included treatment retention, addiction
      severity index results, cocaine craving, mood and anxiety symptoms, cocaine
      withdrawal symptoms, and adverse events. Propranolol treated subjects had lower
      cocaine withdrawal symptom severity but otherwise did not differ from placebo
      treated subjects in any outcome measure. However, in a secondary, exploratory
      analysis, subjects with more severe cocaine withdrawal symptoms responded better
      to propranolol in comparison to placebo. In these subjects, propranolol treatment
      was associated with better treatment retention and lower urinary benzoylecgonine
      levels as compared with the placebo treatment. Propranolol may be useful only for
      the treatment of cocaine dependent patients with severe cocaine withdrawal
      symptoms.

PMID- 11297833
TI  - Does multisite sampling improve patient heterogeneity in drug misuse research?
AB  - The aim of this study was to investigate whether multisite sampling increased
      heterogeneity among a sample of cocaine users from Sao Paulo, Brazil. Six hundred
      and fourteen cocaine users were interviewed at 23 fixed sites plus an out-of
      treatment sample. The sites were then regrouped into six main types: university
      outpatient clinics, public outpatient clinics, public inpatient units, private
      inpatient units, HIV services and non-treatment. Marked differences were found
      between users recruited at these sites, especially in relation to age, gender,
      employment status, criminal history, history of prostitution, previous drug
      misuse treatment, duration of cocaine use and lifetime use of intravenous
      cocaine. These results suggest that multisite sampling is a valid method for
      increasing patient heterogeneity, but whether it improves representativeness and
      thus the generalisability of drug misuse research is debatable.

PMID- 11297834
TI  - Antisocial personality disorder and cocaine dependence: their effects on
      behavioral and electroencephalographic measures of time estimation.
AB  - The present study examined time estimation performance and concurrently-recorded
      electroencephalographic activity among 57 residential treatment program patients
      previously dependent on either cocaine or cocaine and alcohol. The patients were
      assigned to one of two subgroups based upon the presence (n=20) versus absence
      (n=37) of a comorbid diagnosis of Antisocial Personality Disorder (APD). Twenty
      six subjects, who had no history of substance abuse and no diagnosis of APD, were
      also examined. All subjects performed a psychomotor task in which they were asked
      to press a response key exactly 2 s after the onset of a visual cue. Analyses
      revealed that cocaine-dependent patients with APD were often premature in their
      behavioral estimates of time passage. The analysis of a slow EEG potential, viz.
      the Contingent Negative Variation, recorded over the 2 s time estimation
      interval, also suggested premature response preparation in the cocaine-dependent,
      APD-positive group. Correlational analyses revealed that the number of conduct
      problems reported prior to age 15 was a better predictor of both premature
      responding and CNV amplitude than either severity of cocaine dependence, alcohol
      use, or anxious or depressed mood. The potential relevance of these findings for
      studies of future time orientation and delay discounting behavior are discussed.

PMID- 11297835
TI  - Buprenorphine treatment of pregnant opioid--dependent women: maternal and
      neonatal outcomes.
AB  - This open-label prospective study examined maternal and neonatal safety and
      efficacy outcome measures during and following prenatal buprenorphine exposure.
      Three opioid-dependent pregnant women received 8 or 12 mg sublingual
      buprenorphine tablets daily for 15-16 weeks prior to delivery. Results showed
      that buprenorphine in combination with comprehensive prenatal care was safe and
      effective in these women. Prenatal exposure to buprenorphine resulted in normal
      birth outcomes, a mean of 4.33 days (minimum possible=4) hospitalization, and a
      'relatively mild' neonatal abstinence syndrome comprised primarily of tremors
      (disturbed), hyperactive moro and shortened sleep after feeding. The infants
      required no pharmacological treatment. Onset of neonatal abstinence signs
      occurred within the first 12 h after birth, peaked by 72 h and returned to below
      pre-12 h levels by 120 h. It is concluded that buprenorphine has potential
      utility for the treatment of pregnant opioid-dependent women.

PMID- 11297836
TI  - Antitumour activity of Emblica officinalis.
AB  - Aqueous extract of Emblica officinalis (E.O) was found to be cytotoxic to L 929
      cells in culture in a dose dependent manner. Concentration needed for 50%
      inhibition was found to be 16.5 microg/ml. E.O and chyavanaprash (a non-toxic
      herbal preparation containing 50% E.O) extracts were found to reduce ascites and
      solid tumours in mice induced by DLA cells. Animals treated with 1.25 g/kg b.wt.
      of E.O extract increased life span of tumour bearing animals (20%) while animals
      treated with 2.5 g/kg b.wt. of chyavanaprash produced 60.9% increased in the life
      span. Both E.O and chyavanaprash significantly reduced the solid tumours. Tumour
      volume of control animals on 30th day was 4.6 ml where as animals treated with
      1.25 g/Kg b.wt. of E.O extract and 2.5 g/kg b.wt. of chyavanaprash showed a
      tumour volume of 1.75 and 0.75 ml, respectively. E.O extract was found to inhibit
      cell cycle regulating enzymes cdc 25 phosphatase in a dose dependent manner.
      Concentration needed for 50% inhibition of cdc 25 phosphatase was found to be 5
      microg/ml and that needed for inhibition of cdc2 kinase was found to be >100
      microg/ml. The results suggest that antitumour activity of E.O extract may
      partially be due to its interaction with cell cycle regulation.

PMID- 11297838
TI  - Botanical drugs and preparations in the traditional medicine of West Azerbaijan
      (Iran).
AB  - We present the results of an investigation of the traditional ethnobotany and
      ethnomedicine of West Azerbaijan (Iran). In this region medicinal plants are
      often the only easily accessible health care alternative for most of the
      population in rural areas and in fact folk herbal medicine is the most used
      remedy to cure common diseases. In this paper we present the most frequently used
      native species and the most common preparations made from them, in order to
      preserve the plant popular knowledge, which has traditionally been only an oral
      one.

PMID- 11297837
TI  - Patterns of use of unconventional therapies in the medical outpatient department
      of a tertiary care hospital in India.
AB  - Unconventional, alternative or unorthodox systems of treatment have become
      increasingly popular in recent years. We interviewed patients visiting the
      Internal Medicine outpatient department (OPD) for a period of 6 months regarding
      their use of unconventional therapies. Overall 76% of patients visiting the OPD
      had used one or more of the unconventional therapies in the past 1 year.
      Homeopathy was found to be the most frequently used alternative therapy (38.6%).
      A large number of patients used more than one unconventional therapy. Digestive
      problems, backache, joint pains and bronchial asthma were the most frequent
      conditions for which alternative therapies were used. Most patients who used
      alternative therapies used them on their own, without actually visiting a
      provider of such therapies. Because of the widespread use of alternative systems
      of medicine, efforts to enhance understanding about these forms of treatment have
      to be made.

PMID- 11297839
TI  - Evaluation of the gastric antiulcerogenic effect of large cardamom (fruits of
      Amomum subulatum Roxb).
AB  - Large cardamom (fruit of Amomum subulatum Roxb, N.O. Zingiberaceae) commonly
      known as 'Heel kalan' or 'Bari Ilaichi' is used in Unani system of medicine in
      gastrointestinal disorders. A crude methanolic extract and its different
      fractions, viz. essential oil, petroleum ether (60-80 degrees ), ethyl acetate
      and methanolic fractions, were studied in rats for their ability to inhibit the
      gastric lesions induced by aspirin, ethanol and pylorus ligature. In addition
      their effects on wall mucus, output of gastric acid and pepsin concentration were
      recorded. The crude methanolic extract of A. subulatum and its fractions, viz.
      essential oil, petroleum ether and ethyl acetate, inhibited gastric lesions
      induced by ethanol significantly, but not those which were induced by pylorus
      ligation and aspirin. However, ethyl acetate fraction increased the wall mucus in
      pylorus ligated rats. The results suggest a direct protective effect of ethyl
      acetate fraction on gastric mucosal barrier. While the observation of decrease in
      gastric motility by essential oil and petroleum ether fractions suggests the
      gastroprotective action of the test drug. These investigations validate the use
      of 'Heel kalan' in gastrointestinal disorders by Unani physicians.

PMID- 11297840
TI  - Traditional medicine in Turkey X. Folk medicine in Central Anatolia.
AB  - Traditional medicine used in Central Anatolia; Ankara, Kayseri, Nigde and south
      eastern parts of Karaman and Konya provinces have been studied. Two hundred and
      ninety one folk remedies obtained from 103 plant species belonging to 40 families
      and 4 animal species are reported with their vernacular names, parts used,
      methods of preparing remedies and therapeutic usage.

PMID- 11297841
TI  - Analgesic and antipyretic effects of Dodonaea angustifolia and Salvia africana
      lutea.
AB  - Water extracts of Dodonaea angustifolia L. and Salvia africana-lutea L., were
      investigated for analgesic and antipyretic activities using acetic acid writhing
      and hot plate tests, and lipopolysaccharide (LP)-induced pyrexia test in mice and
      rats, respectively. D. angustifolia and S. africana-lutea significantly inhibited
      acetic acid-induced writhing and also significantly delayed the time of reaction
      of mice to thermal stimulation produced by the hot plate. D. angustifolia and S.
      africana-lutea significantly reduced fever induced by LP. Paracetamol produced
      similar effects to D. angustifolia and S. africana-lutea on the acetic acid
      induced writhing but has no effect on hot plate-induced nociception and on
      pyrexia produced by LP. These data indicate the analgesic and antipyretic
      potential of D. angustifolia and S. africana-lutea.

PMID- 11297842
TI  - Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance
      of ursolic acid.
AB  - Salvia officinalis L. leaves, obtained from four plant populations of different
      origin, were investigated for their topical anti-inflammatory properties. The n
      hexane and the chloroform extracts dose-dependently inhibited the Croton oil
      induced ear oedema in mice, the chloroform extracts being the most active. By
      contrast, the methanol extracts showed a very low effect and the essential oil
      was inactive. Chemical and pharmacological investigation of the most potent
      chloroform extract, issued from an autochthonous sage population grown in the
      submediterranean climatic region of Slovenia, revealed ursolic acid as the main
      component involved in its anti-inflammatory activity. The anti-inflammatory
      effect of ursolic acid (ID50 = 0.14 microMoles/cm2) was two fold more potent than
      that of indomethacin (ID50 = 0.26 microMoles/cm2), which was used as a reference
      non-steroidal anti-inflammatory drug (NSAID). The content of ursolic acid in sage
      and sage-based remedies for the topical treatment of inflammatory diseases is
      proposed as a parameter for quality control purposes.

PMID- 11297843
TI  - Constituents of Chinese Piper species and their inhibitory activity on
      prostaglandin and leukotriene biosynthesis in vitro.
AB  - The n-hexane extracts of 19 Piper species, predominantly from China, were
      screened for their 5-lipoxygenase (5-LOX) and cyclooxygenase-1 (COX-1) inhibitory
      potential. Many of them showed considerable inhibitory activity against at least
      one of these two key enzymes of the arachidonic acid metabolism, especially
      against COX-1. The best results in inhibiting the formation of leukotrienes were
      obtained with the extract of Piper kadsura. In the terms of prostaglandin
      synthesis inhibition, the extract of Piper boehmeriifolium var. tonkinense was
      found to have the strongest activity. Furthermore, an analytical investigation by
      means of TLC, HPLC-DAD and GC-MS resulted in the identification of 20
      constituents. Most of them were amides with an interesting variety of amine
      moieties. Among them were pellitorine, and four higher homologues,
      piperlonguminine, dihydropiperlonguminine, futoamide, chingchengenamide, the
      retrofractamides A, B and D, guineensine, brachystamide B, piperanine, piperine,
      piperdardine, sarmentine, pipataline and benzylbenzoate. In 96 cases, these
      constituents were new for the particular plant.

PMID- 11297844
TI  - Should we be concerned about herbal remedies.
AB  - During the latter part of this century the practice of herbalism has become
      mainstream throughout the world. This is due in part to the recognition of the
      value of traditional medical systems, particularly of Asian origin, and the
      identification of medicinal plants from indigenous pharmacopeias that have been
      shown to have significant healing power, either in their natural state or as the
      source of new pharmaceuticals. Generally these formulations are considered
      moderate in efficacy and thus less toxic than most pharmaceutical agents. In the
      Western world, in particular, the developing concept that 'natural' is better
      than 'chemical' or 'synthetic' has led to the evolution of Neo-Western herbalism
      that is the basis of an ever expanding industry. In the US, often guised as food,
      or food supplements, known as nutriceuticals, these formulations are readily
      available for those that wish to self-medicate. Within this system, in
      particular, are plants that lack ethnomedical verification of efficacy or safety.
      Unfortunately there is no universal regulatory system in place that insures that
      any of these plant remedies are what they say they are, do what is claimed, or
      most importantly are safe. Data will be presented in this context, outlining how
      adulteration, inappropriate formulation, or lack of understanding of plant and
      drug interactions have led to adverse reactions that are sometimes life
      threatening or lethal.

PMID- 11297845
TI  - Effect of Withania somnifera on DMBA induced carcinogenesis.
AB  - Administration of an extract of Withania somnifera was found to reduce two stage
      skin carcinogenesis induced by DMBA (dimethyl benzanthracene) and croton oil.
      Withania somnifera was administered at a concentration of (20 mg/dose/animal
      i.p.) consecutively on 5 days prior to DMBA administration and continued twice
      weekly for 10 weeks. After the 180th day of carcinogen administration, all of the
      animals developed papilloma in the control group whereas only six out of 12
      animals developed papilloma in the treated group. A total of 11 papillomas were
      found in the control group while only six developed them in the Withania
      somnifera treated group. Enzyme analysis of skin and liver showed significant
      enhancement in antioxidant enzymes such as GSH, GST, Glutathione peroxides and
      Catalases in Withania somnifera treated group when compared with the control. The
      elevated level of lipid peroxide in the control group was significantly inhibited
      by Withania somnifera administration. These studies indicate that Withania
      somnifera could reduce the papilloma induced alterations to the antioxidant
      defense systems.

PMID- 11297846
TI  - Evaluation of the protective potential of Ambrosia maritima extract on
      acetaminophen-induced liver damage.
AB  - The hepatoprotective activity of the aqueous-methanolic extract of Ambrosia
      maritima was investigated against acetaminophen (paracetamol, 4-hydroxy
      acetanilide) induced hepatic damage. Acetaminophen at the dose of 640 mg/kg
      produced liver damage in rats as manifested by the significant (P < 0.001) rise
      in serum levels of glutamate oxaloacetate transaminase (AST), glutamate pyruvate
      transaminase (ALT) and alkaline phosphatase (ALP) to 1178.5 +/-118.05; 607.5 +/-
      32.6 and 274.16 +/- 8.89 IU/l (n = 10), respectively, compared with respective
      control values of 97.83+/-3.23; 46.0 +/- 3.92 and 168.67 +/- 7.86 IU/l.
      Pretreatment of rats with the plant extract (100 and 200 mg/kg) lowered
      significantly (P < 0.001) the respective serum AST to 203.3+/-5.74 and 157.1 +/-
      8.78 IU/l, ALT to 138.67 +/- 7.7 and 87.5 +/- 3.6 IU/l and ALP levels to 238.0 +/
      5.89 and 206.5 +/- 7.5 IU/l, respectively. Treatment of rats with acetaminophen
      led to a marked increase in lipid peroxidation as measured by malondialdehyde
      (MDA) (42%). This was associated with a significant reduction of the hepatic
      antioxidant system e.g. reduced glutathione (GSH) (65%), glutathione reductase
      (GSH-R) (35%), total glutathione peroxidase (GSH-Px) (32%) and glutathione-S
      transferase (GST) (16%). These biochemical alterations resulting from
      acetaminophen administration were inhibited by pretreatment with A. maritima L.
      extract. These data suggest that the plant A. maritima L. may act as a
      hepatoprotective and antioxidant agent.

PMID- 11297847
TI  - Effects of Mucuna pruriens extract on activation of prothrombin by Echis
      carinatus venom.
AB  - Mucuna pruriens (L.) DC has long been used as a medicinal plant by traditional
      healers. The validity of the claims made for this plant has also been tested
      scientifically. Some of its properties are probably linked to high concentrations
      of dopa since it is useful in the treatment of Parkinson's disease. The antisnake
      properties of an extract of Mucuna pruriens' seeds (MP101UJ) in vivo were
      recently demonstrated and one is now investigating its biochemical mechanism.
      Echis carinatus venom (EV) contains a mixture of proteins that affect the
      coagulative cascade, causing severe bleeding and haemorrhage. Here the effect of
      an extract of MP101UJ in prothrombin activation by EV in vitro by clotting and
      chromogenic assay is studied. An increase in procoagulant activity was found.
      This could explain the protective effect in vivo.

PMID- 11297848
TI  - Effect of 'antidiabetis' herbal preparation on serum glucose and fructosamine in
      NOD mice.
AB  - The antihyperglycemic effect of the Antidiabetis herbal preparation ((Myrtilli
      folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum officinale Web.),
      Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.),
      Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli pericarpium (Phaseolus
      vulgaris), Millefollii herba (Achillea millefolium L.), Morii folium (Morus nigra
      L.), Valeriane radix (Valleriana officinalis L.), Urticae herba et radix (Urtica
      dioica L.)), patent No. P-9801091 Zagreb, Croatia was investigated. Two extracts
      were prepared: ethanol extract (extract 1), and ethanol extract from which
      ethanol was evaporated on a rotatory evaporator at a temperature of 45 degrees C
      (extract 2). Extract 1 and extract 2 were administered (in experiment 1) to
      alloxan-induced non-obese diabetic (NOD) mice in the same dose of 20 mg/kg. Blood
      glucose was determined before, and 10, 30, 60 and 120 min after the preparation
      administration. Extract 1 and extract 2 decreased the level of blood glucose by
      10 and 20%, respectively, of the initial value (at 0 min, mean = 22.6 +/- 8.3
      mmol/l). Serum levels of glucose and fructosamine were determined in NOD mice,
      NOD mice administered extract 2 in a dose of 20 mg/kg of extract 2, and NOD mice
      administered acarbose in a dose of 25 mg/100 g chow, in order to verify the
      hypoglycemic action of extract 2 (in experiment 2). Extract 2 and acarbose were
      admixed to the chow. The duration of treatment was 7 days. Significantly lower
      glucose (P < 0.05) and fructosamine (P < 0.001) levels were recorded in extract 2
      treated NOD mice as compared with NOD mice. Study results showed extract 2 to
      significantly decrease the level of glucose and fructosamine in alloxan induced
      NOD mice. Our future studies will be focused on the search of active principles
      of the extracts.

PMID- 11297849
TI  - Diuretic effects of selected Thai indigenous medicinal plants in rats.
AB  - Extracts of five indigenous Thai medicinal having ethnomedical application in the
      treatment of dysuria were investigated for their diuretic activity. Root extracts
      of Ananas comosus and Carica papaya, given orally to rats at a dose of 10 mg/kg,
      demonstrated significantly increased urine output (P < 0.01) which was 79 and
      74%, respectively, of the effect of an equivalent dose of hydrochlorothiazide.
      Both plant extracts gave similar profiles of urinary electrolyte excretion to
      that of the hydrochlorothiazide. The analyses of the urinary osmolality and
      electrolyte excretion per unit time suggest the observed effect of A. comosus was
      intrinsic, whereas that of C. papaya may have resulted from a high salt content
      of this extract. However, our experimental evidence on the diuretic activities of
      the other three plants did not parallel their local utilization for dysuria. It
      was found that the rhizome of Imperata cylindrica apparently inhibited the
      urination of rats whereas the rhizome of Cyperus rotundus and the stem of
      Averrhoa carambola failed to demonstrate any diuretic activities. These results
      indicate that two of the plants investigated exert their action by causing
      diuresis. The other three plants need further investigation to determine their
      effectiveness in the treatment of dysuria.

PMID- 11297850
TI  - Evaluation of the oral hypoglycaemic effect of Trigonella foenum-graecum L.
      (methi) in normal mice.
AB  - Trigonella foenum-graecum (Fenugreek) (Leguminosae) is employed as a herbal
      medicine. Its seeds are known for their carminative, tonic and antidiabetic
      effects. A curative dose of Trigonella foenum-graecum also produces antiulcer
      action. In this study we have investigated the hypoglycaemic activities of the
      aqueous extract of the seeds Trigonella foenum-graecum in normal mice using oral
      route of adminstration. The methanolic extract administered through the same
      route produced hypoglycaemic effect only at the dose of 1 g/kg body weight. The
      aqueous extract is under further investigation to determine the chemical
      structure of the active component. The presence of hypoglycaemic activity in
      aqueous and methanolic extract indicates that the active compounds are polar in
      nature.

PMID- 11297851
TI  - Effect of chronic treatment with bark of Terminalia arjuna: a study on the
      isolated ischemic-reperfused rat heart.
AB  - Dried pulverized bark of Terminalia arjuna Linn (TA) was administered orally to
      Wistar albino rats (120-150 g) in two doses [500 and 750 mg/kg in 2% carboxy
      methyl cellulose (CMC)], 6 days per week for 12 weeks. Thereafter, rats were
      sacrificed either for determination of baseline changes in cardiac endogenous
      antioxidant compounds [superoxide dismutase (SOD), reduced glutathione (GSH) and
      catalase (CAT)] or the hearts were subjected to oxidative stress associated with
      in vitro ischemic-reperfusion injury (IRI). There was significant increase in the
      baseline contents of thiobarbituric acid reactive substance (TBARS) (a measure of
      lipid peroxidation) with both doses of TA. However, only in the 500 mg/kg treated
      group, this was accompanied by a simultaneous increase in SOD, GSH and CAT
      levels, but not in the 750 mg/kg treated group, where only CAT was raised.
      Significant rise in myocardial TBARS and loss of SOD, CAT and GSH (suggestive of
      increased oxidative stress) occurred in the vehicle-treated hearts subjected to
      in vitro IRI. Only hearts, harvested from the 500 mg/kg rats treated rats, were
      significantly protected from oxidative stress, when subjected to in vitro IRI.
      The results suggest that crude bark of TA augments endogenous antioxidant
      compounds of rat heart and also prevents oxidative stress associated with IRI of
      the heart.

PMID- 11297852
TI  - Anti-Helicobacter pylori activity of Aristolochia paucinervis Pomel extracts.
AB  - The anti-Helicobacter pylori effect of the extracts and the fractions obtained
      from Aristolochia paucinervis rhizome and leaves were studied against a reference
      strain of H. pylori by using the agar dilution method. Only the methanol extracts
      and the hexane fractions of either the rhizome or the leaves exhibited an
      inhibitory activity at a concentration of < or =128 microg/ml. The leaf hexane
      fraction APLH demonstrated a higher inhibitory activity (MIC: 4 microg/ml) than
      the rhizome hexane fraction APRH (MIC: 16 microg/ml), the leaf methanol extract
      APLM (MIC: 32 microg/ml) and the rhizome methanol extract APRM (MIC: 128
      microg/ml). This inhibitory activity was confirmed for the active extracts and
      fractions against clinical isolates of H. pylori (n = 20) for which MIC50) and
      MIC90 were determined.

PMID- 11297853
TI  - Bactericidal properties of the chloroform fraction from rhizomes of Aristolochia
      paucinervis Pomel.
AB  - The deffated chloroform fraction (APRC) obtained from the rhizomes of
      Aristolochia paucinervis Pomel (Aristolochiaceae) has a high bacteriostatic
      activity against bacterial strains like Clostridium perfringens ATCC 13124 and
      Enterococcus faecalis ATCC 29212. Here, we report the bactericidal activity of
      APRC against both strains which was evaluated by using time-to kill assays. The
      results showed that APRC produced an intense time-dependent bactericidal effect
      against C. perfringens, achieving over a 24 h-period a 5log10-unit decrease in
      CFU/ml at a concentration > or =1.25 x MIC. In contrast, when tested against E.
      faecalis, APRC exhibited a concentration-dependent killing activity at
      concentrations of 1.25 x MIC and 2.5 x MIC, yielding to a decrease of 1.5 and
      2.5log10-unit in CFU/ml at 4 h, respectively. However, substantial regrowth of E.
      faecalis occurred within 24 h. Ultrastructural alterations were observed for both
      exposed microorganisms by scanning and transmission electron microscopy.

PMID- 11297855
TI  - Chronic diuretic effect of the water extract of Spergularia purpurea in normal
      rats.
AB  - The purpose of this study was to examine the chronic diuretic effect of the water
      extract of the whole plant of Spergularia purpurea (SP) at different doses (100,
      200 and 400 mg/kg) in normal rats. Daily oral administration of the water extract
      was tested for 4 weeks. Urinary water and electrolytes excretion were determined
      weekly. Oral administration of the water extract at different doses produced a
      significant and dose-dependent diuresis and increase in electrolytes excretion.
      The highest dose (400 mg/kg) of the water extract of SP enhanced urine output
      from 7.15 +/- 0.42 ml/24 h at the start to 23.01 +/- 0.75 ml/24 h after 4 weeks
      (p < 0.001). It also produced significant increase in urinary excretion of Na+ (P
      < 0.01), K+ (P < 0.01) and Cl(-) (P < 0.01). Chronic treatment with SP decreased
      significantly urine osmolality (P < 0.01 vs. control), while a slight increase in
      glomerular filtration rate was also observed (P < 0.05) for both doses of water
      extract (100 and 400 mg/kg). It is concluded that the water extract of whole
      plant of SP has a significant diuretic effect in rats.

PMID- 11297854
TI  - Potent anti-inflammatory activities of hydroalcoholic extract from aerial parts
      of Stachys inflata on rats.
AB  - Extracts obtained from aerial parts of Stachys inflata have been used in Iranian
      folk medicine in infective, rheumatic and other inflammatory disorders. In the
      present study, the anti-inflammatory properties of total methanol extract
      isolated from aerial parts of Stachys inflata were investigated in two well
      characterised inflammatory models in rats, carrageenan-induced paw oedema and
      formalin-induced paw licking. Intraperitoneal injection of the extract, 60 min
      before induction of inflammation, revealed a dose-related inhibition of
      carrageenan-induced rat paw oedema over the dose range 50-200 mg/kg. In the
      formalin test, the extract (50, 100 and 200 mg/kg) had no effect against the
      first phase (0-5 min) of the formalin-induced pain, but all three doses produced
      a significant blockade of the second phase (P < 0.001). Myeloperoxidase (MPO)
      activity was determined, and a histopathological study was carried out in paw
      tissue 4 h after induction of inflammation. The hydroalcoholic extract (200
      mg/kg) substantially reduced MPO activity (P < 0.05), which was increased in the
      control group. Histological examination showed a marked reduction in tissue
      injury and inhibition in neutrophil infiltration in rats treated with the extract
      (200 mg/kg).

PMID- 11297856
TI  - Lepidium meyenii Walp. improves sexual behaviour in male rats independently from
      its action on spontaneous locomotor activity.
AB  - Lepidium meyenii Walpers (Maca) is traditionally employed in the Andean region
      for its supposed properties to improve energy and fertility. The aim of this
      study was to evaluate the effect of acute and chronic Maca pulverised root oral
      administration on rat sexual behaviour. Sixty male sexually experienced rats (20
      group) were daily treated for 15 days with Maca 15 mg kg(-1), Maca 75 mg kg(-1)
      or saline 0.5 ml kg(-1). The following sexual performance parameters were
      evaluated at first and last day of treatment: 1st mount (ML), 1st intromission
      (IL), ejaculation (EL) and postejaculatory (PEL) latencies, intercopulatory
      interval (ICI) and copulatory efficacy (CE). An activity cage test was carried
      out to evaluate if Maca-induced locomotion changes could indirectly improve rat
      sexual performances. It was observed that both lower and higher Maca doses
      acutely decreased ML, IL and ICI in a significant way (P < 0.05), while only the
      75 mg kg(-1) dose decreased the PEL (T = 29, P < 0.05). This effect seems to be
      the only one dose-dependent. After 15 days of treatment, both doses are able to
      significantly decrease ML, IL, EL and PEL, while the 75 mg kg(-1) dose decreased
      the ICI (T = 40, P < 0.05) too. IL, EL and PEL variations seem to be dose-related
      after chronic treatment. Moreover, chronic Maca treatment induced an apparently
      not dose-related increase in rat locomotion, during the second 10-min period of
      observation in the activity cage. The late in Maca-induced locomotion
      modification excludes that improvement of tested sexual performance parameters is
      related to an increase in rat aspecific activity. Thus, it was concluded that
      both acute and chronic Maca oral administration significantly improve sexual
      performance parameters in male rats.

PMID- 11297857
TI  - Some less known ethnomedicinal uses from Mysore and Coorg districts, Karnataka
      state, India.
AB  - Present communication deals with 76 ethnomedicinal plants being used
      traditionally in Karnataka, India. These plants are reported to have 78 less
      known ethnomedicinal uses for curing various skin diseases, cuts, stomach
      disorders, gynaecological complaints and snakebites.

PMID- 11297859
TI  - Screening of several Indonesian medicinal plants for their inhibitory effect on
      histamine release from RBL-2H3 cells.
AB  - Twelve alcoholic extracts and 12 hexane extracts of plant materials selected on
      the basis of medicinal folklore for asthma treatment in Indonesia were studied
      for their activity in inhibiting histamine release from RBL-2H3 cells (rat
      basophilic leukemia cell line), a tumor analog of mast cells. The results of
      screening indicated that five alcoholic extracts (Plantago major leaves,
      Eucalyptus globulus leaves and fruit, Cinnamomum massoiae cortex, Vitex trifolia
      leaves) and two hexane extracts (Eucalyptus globulus leaves, Vitex trifolia
      leaves) inhibited IgE-dependent histamine release from RBL-2H3 cells. The
      inhibitory effects were found to be more than 80% for extract concentrations of
      0.5 mg/ml. The results indicate that the extracts contain active compounds that
      inhibit mast-cell degranulation, and provide insight into the development of new
      drugs for treating asthma and/or allergic disease.

PMID- 11297858
TI  - Screening of various Swertia species extracts in primary monolayer cultures of
      rat hepatocytes against carbon tetrachloride- and paracetamol-induced toxicity.
AB  - Swertia chirata Buch-Ham. (Gentianaceae), one of the oldest medicinal herbs of
      India, is a source of the Indian ayurvedic drug 'chirata' used for the treatment
      of liver disorders and malarial fevers. In this study, eight species of Swertia
      were collected. Each of the dry whole plant was extracted into methanol, the
      aqueous extract of which was sequentially extracted into hexane, chloroform and
      butanol extracts. The extracts were screened for their anti-hepatotoxic activity
      against carbon tetrachloride (CCl4) and paracetamol (acetaminophen (AAP))
      toxicity in primary monolayer cultures of rat hepatocytes. The primary cultures,
      2.5 x 10(6) cells /3 ml medium/60 mm collagen-coated plates, were exposed to 2.5
      mM CCl4 or 12 mM AAP in the presence or absence of plant extracts (100 microg/ml
      culture medium). Cells and medium were harvested after 22 h of treatment for the
      assay of cellular reduced gluthathione (GSH) content and leakage of lactate
      dehydrogenase as biological end-points of toxicity. Both CCl4 and AAP at the
      indicated concentrations reduced GSH by almost 50 and 80%, respectively, while
      the enzyme leakage was almost 15% above the untreated control. Hexane and
      methanol extracts of most of the species in general offered relatively good
      protection. The anti-hepatotoxic activity, nevertheless, was evident in all
      Swertia species against both the toxicants. However, Swertia purpurascens,
      Swertia chirata, Swertia paniculata and Swertia cordata exhibited better activity
      compared with other species investigated. In addition, influence of various
      extracts (10-100 microg/ml medium) was examined on cellular growth of rat Reuber
      hepatoma cell line H4IIEC3/G-. Except for the butanol extract of S. chirata, no
      other extracts exerted toxicity in terms of neutral red uptake by the cells.

PMID- 11297860
TI  - COX-1 inhibitory activity in extracts from Eucomis L'Herit. species.
AB  - Non-steroidal anti-inflammatory compounds can relieve pain and inflammation
      associated with elevated levels of prostaglandins in the body and are proposed to
      be the agents responsible for the action of traditional herbal remedies
      associated with the reduction of pain, fever and inflammation. Primarily the
      bulbs and in some instances the leaves and roots, of Eucomis L 'Herit. species
      are widely utilized in South African traditional medicine for this purpose. A
      measure of the anti-inflammatory activity of plant extracts can be generated
      using the cyclooxygenase (COX-1) assay. High levels of COX-1 inhibitory activity
      were detected in crude extracts prepared from the leaves, bulbs and roots of
      Eucomis species. Of the 11 species tested, 9 species exhibited moderate COX-1
      inhibitory activity (40-70%) for the aqueous bulb extracts. All 11 species showed
      COX-1 inhibitory activity of +/-70% or higher, for the ethanol bulb extracts. The
      bulb and root extracts (ethanol) showed, in general, the highest levels of COX-1
      inhibitory activity, but most species exhibited no significant difference in
      activity between plant parts. Generally (for 7 of the 11 species), these levels
      did not differ significantly in specimens harvested in summer and in winter. IC50
      values were calculated to be 72 microg ml(-1) for the bulb extract of E.
      autumnalis autumnalis, and 27 microg ml(-1) for the root extracts. The
      corresponding IC50 value for the leaf extract was estimated to be 15 microg ml(
      1). The COX-1 inhibitors were relatively stable over time, both in solution
      (ethanol) and in the dried plant material. Extracts tested over a period of three
      years did not differ significantly in COX-1 inhibitory activity. These
      experimental results validate the extensive use of this plant in southern African
      traditional medicine.

PMID- 11297861
TI  - Effects of paeoniflorin on the formalin-induced nociceptive behaviour in mice.
AB  - In this study, we attempted to identify the mechanisms of paeoniflorin on
      antinociceptive effects in mice. Paeoniflorin (48, 96, 240, 480 microg, i.c.v.)
      showed dose-related antinociception both on the early and late phases of formalin
      test in mice. Moreover, paeoniflorin (48 microg, i.c.v.) could potentiate the
      antinociception of morphrine (0.5, 1.0 mg/kg, s.c.) in the formalin test.
      However, the antinociceptive effects of paeoniflorin were not potentiated by L
      arginine (600 mg/kg, i.p.) or antagonized by beta-funaltrexamine (beta-FNA) (10
      microg, i.c.v.), ICI-174,864 (1 microg, i.c.v.) and ryanodine (10 ng, i.c.v.) on
      both the early and late phases of formalin test. L-NAME (75 mg/kg, i.p.) could
      reverse the effect of paeoniflorin on the late phase of formalin test. Naloxone
      (1 mg/kg, i.p.) and nor-binaltorphimine (nor-BNI) (1 microg, i.c.v.) could block
      the paeoniflorin-induced antinociception on the early phase of formalin test.
      These results suggested that the central antinociceptive effects of paeoniflorin
      on formalin test in mice were mediated by the activation of kappa-opioid receptor
      and not related to the increase of intracellular calcium.

PMID- 11297862
TI  - Xanthine oxidase inhibitory activity of selected Australian native plants.
AB  - Twenty-eight extracts from 17 species of Australian native plants traditionally
      used as general anti-inflammatory medicines by Australian Aboriginal people were
      examined for inhibition of the enzyme xanthine oxidase (XO). The extracts from
      nine species were found to have more than 25% inhibition at a concentration of
      100 microg/ml in the assay mixture. Extracts from three species Clerodendrum
      floribundum R. Br. (Verbenaceae), Eremophila maculata (Ker Gawler) (Myoporaceae)
      and Stemodia grossa Benth. (Scrophulariaceae) showed the greatest activity with
      inhibitions of 84, 61 and 57%, respectively, at 50 microg/ml, with four other
      species having more than 40% inhibitory activity at this concentration.

PMID- 11297863
TI  - Anti-inflammatory activity of cubebin, a lignan from the leaves of Zanthoxyllum
      naranjillo Griseb.
AB  - Cubebin, a dibenzylbutyrolactone lignan isolated from the crude hexane extract of
      the leaves of Zanthoxyllum naranjillo, showed a significant anti-inflammatory
      activity by using the paw edema induced by carrageenin in rats, but did not
      provide a significant reduction in the cell migration for the acute carrageenin
      induced inflammatory reaction in the peritoneal cavity of rats. Neither was it
      effective in reducing the edema induced by dextran nor the edema induced by
      histamine. It partially reduced the edema induced by serotonin. Moreover, it
      significantly reduced the edema induced by prostaglandin PGE2 and the number of
      writhings induced by both acetic acid and PGI2 in mice. Therefore, it may be
      suggested that the mechanism of action of cubebin is similar to that observed for
      most of the non-steroidal drugs.

PMID- 11297864
TI  - Anti-inflammatory and antipyretic effects of Trigonella foenum-graecum leaves
      extract in the rat.
AB  - Anti-inflammatory and antipyretic effects of the Trigonella foenum-graecum (TFG)
      leaves extract, an Iranian medicinal plant, were examined. For anti-inflammatory
      activity, the formalin-induced edema model was used. Hyperthermia was induced by
      intraperitoneal injection of 20% (w/v) aqueous suspension of brewer's yeast.
      Sodium salicylate (SS) was used as a positive control. Both TFG and SS
      significantly reduced formalin-induced edema in single dose (TFG 1000 and 2000
      mg/kg, SS 300 mg/kg) and chronic administration (TFG 1000 mg/kg and SS 300
      mg/kg). TFG and SS also significantly reduced hyperthermia induced by brewer's
      yeast in 1 and 2 h after their administration. The results indicate that the TFG
      leaves extract possess anti-inflammatory as well as antipyretic properties in
      both i.p. and p.o. administration. Phytochemical studies indicate that alkaloids,
      cardiac glycosides, and phenols are the major component in the extract. Although
      existence of three anti-inflammatory, analgesic and antipyretic effects in this
      extract suggest a NSAID-like mechanism for it, but the presence of alkaloids, the
      absence of other effective compounds such as flavonoids, saponins, steroids,
      etc., and also its analgesic effect on tail-flick test that usually is not
      produced by NSAIDs, suggest another mechanism for the extract. So the possibility
      of alkaloids as effective compounds, in this extract, increases.

PMID- 11297865
TI  - Inhibitory effects of xanthones on platelet activating factor receptor binding in
      vitro.
AB  - Nine naturally occurring xanthones were investigated for their platelet
      activating factor (PAF) receptor binding inhibitory effects using rabbit
      platelets. 2-(3-methylbut-2-enyl)-1,3,5-trihydoxyxanthone, macluraxanthone, 1,3,5
      trihydroxy-6,6'-dimethylpyrano(2',3':6,7)-4-(1,1-dimethylprop-2-enyl)xanthone, 6
      deoxyjacareubin and 2-(3-methylbut-2-enyl)-1,3,5,6-terahydroxyxanthone showed
      strong inhibition with IC50 values of 4.8, 11.0, 21.0, 29.0 and 44.0 microM,
      respectively. The prenyl group at C-2, the dimethylprop-2-enyl group at C-4 and
      the hydroxyl group at C-5 are all beneficial to the binding of xanthones to the
      PAF receptor. The results revealed that xanthones can represent a new class of
      natural PAF receptor antagonists.

PMID- 11297866
TI  - Choleretic effect and intestinal propulsion of 'mate' (Ilex paraguariensis) and
      its substitutes or adulterants.
AB  - 'Mate' or 'Yerba mate' (Ilex paraguariensis, Aquifoliaceae) is a tonic and
      stimulant beverage widely used in South America. It is also traditionally used in
      gastrointestinal disorders as eupeptic and choleretic agent. Accordingly, the
      effect of decoctions of the leaves of I. paraguariensis and three of its
      substitutes or adulterants (Ilex brevicuspis, Ilex argentina and Ilex theezans)
      on bile flow (BF) and intestinal propulsion were investigated. I. paraguariensis
      and I. brevicuspis induced an increase in BF, while the latter also enhanced
      intestinal transit. In contrast, neither I. argentina nor I. theezans exerted any
      effect on BF or intestinal propulsion. These results suggest that the therapeutic
      properties of I. paraguariensis will be affected when at least an adulterant is
      present in the final commercial product of Yerba mate.

PMID- 11297867
TI  - Biphasic membrane effects of capsaicin, an active component in Capsicum species.
AB  - Capsaicin, an active component in Capsicum species, not only stimulates sensory
      afferent neurons but also inhibits bacterial growth and platelet aggregation. To
      address the pharmacological mechanism of non-neuronal actions, the effects of
      capsaicin and its structural analog (N-vanillylnonanamide) on membrane fluidity
      were studied by measuring fluorescence polarization of liposomes prepared with
      different phospholipids and cholesterol. Capsaicin and the analog changed
      membrane fluidity over the concentration range of 50-500 microM differentially
      with varying concentrations and membrane lipid composition. They showed biphasic
      effects on 100 mol% 1-palmitoyl-2-oleoylphosphatidylcholine liposomes and 40 mol%
      cholesterol-containing 1-palmitoyl-2-oleoylphosphatidylcholine liposomes to
      fluidize and rigidify both liposomal membranes at low and high concentrations,
      respectively. Changes in membrane fluidity occurred at concentrations
      corresponding to their reported antibacterial and antiplatelet concentrations.
      Antibacterial (geraniol and lidocaine) and antiplatelet reference compounds (4
      ethylphenol and benzyl alcohol) concentration-dependently fluidized membranes,
      while not showing biphasic effects. Comparing the potency to fluidize membranes,
      capsaicin was almost comparable to geraniol and 4-ethylphenol, and more active
      than lidocaine and benzyl alcohol. The membrane effects of capsaicinoids are
      responsible for their non-neuronal antibacterial and antiplatelet actions,
      although they are not the simple membrane fluidizers.

PMID- 11297868
TI  - Placental transfer of the soy isoflavone genistein following dietary and gavage
      administration to Sprague Dawley rats.
AB  - Genistein, the principal soy isoflavone, has estrogenic activity and is widely
      consumed by humans for putative beneficial health effects. The goal of the
      present study was to measure placental transfer of genistein in rats as a
      possible route of developmental exposure. Pregnant Sprague-Dawley rats were
      administered genistein orally, either by diet or by gavage. Concentrations of
      genistein aglycone and conjugates were measured in maternal and offspring serum
      and brain using HPLC with isotope dilution electrospray tandem mass spectrometry.
      Although fetal or neonatal serum concentrations of total genistein were
      approximately 20-fold lower than maternal serum concentrations, the biologically
      active genistein aglycone concentration was only 5-fold lower. Fetal brain
      contained predominately genistein aglycone at levels similar to those in the
      maternal brain. These studies show that genistein aglycone crosses the rat
      placenta and can reach fetal brain from maternal serum genistein levels that are
      relevant to those observed in humans.

PMID- 11297869
TI  - Light irradiation increases embryotoxicity of photodynamic therapy sensitizers (5
      aminolevulinic acid and protoporphyrin IX) in chick embryos.
AB  - Photodynamic therapy (PDT) of malignant processes is based on the ability of a
      photosensitizer to first, accumulate in malignant (immature) tissue and second,
      to be destroyed following light irradiation. Because of the similarity between
      malignant and embryonic immature tissues, we investigated the deleterious effect
      of the PDT procedure on day 4 chick embryos in ovo. We compared experimentally
      the photodynamic effect (light-toxic) and the side effect (dark-toxic) of the
      clinically attractive photosensitizers 5-aminolevulinic acid (ALA) and
      protoporphyrin IX (PP IX). The dark and light embryotoxicity (i.e. lethality plus
      teratogenicity) was determined after intra-amniotic injection of one of a range
      of dose of each compound. Under dark conditions, PP IX exhibited embryotoxicity
      at a dose of 10 microg/embryo; however ALA did not exhibit embryotoxicity even at
      the highest dose (300 microg/embryo). Light irradiation of embryos following
      injection induced strong embryotoxic effects of both substances even at dark
      ineffective doses.

PMID- 11297871
TI  - Impact of chronic low-dose ethanol ingestion during sexual maturation of female
      mice on in-vitro and in-vivo embryo development.
AB  - Little is known of the consequences of ethanol intake prior to fertilization on
      preimplantation embryo development. Recently we showed that chronic 10 and 5% w/v
      ethanol intake by young female mice reduces in vitro fertilization (IVF) rates.
      The purpose of the present work was to investigate whether the adverse effects of
      preconceptional low-dose chronic ethanol intake by sexually maturing female mice
      affects preimplantation embryo growth in vitro or in vivo in subsequent
      pregnancy. Prepubertal female mice were given 5% ethanol in their drinking water
      for 30 days. On day 27 and 29 of the ethanol treatment, females were
      superovulated. IVF-derived cultured embryos (in vitro development) or embryos
      obtained from oviducts and uteri (in vivo development) were evaluated. Whether
      analyzed on a per embryo or per dam basis, ethanol treatment was associated with
      a significant decrease in progression through embryo stages during the seven days
      of in vitro development and with an increase in morphologically abnormal embryos.
      Progression through embryo stages during four days of in vivo development was
      also inhibited by ethanol pretreatment of dams At 99 h post-hCG of in vivo
      development, there were fewer total, hatched, and expanded blastocysts, and a
      complete absence of implanting blastocysts among females treated with ethanol. In
      summary, low-dose chronic ethanol consumption of sexually maturing female mice
      prior to conception has adverse effects on preimplantation embryo development,
      both under in vitro and in vivo conditions, manifested as retarded development,
      embryo anormalities, and a reduction in expansion and hatching of the
      preimplantation blastocyst.

PMID- 11297870
TI  - Developmental toxicity of an octyltin stabilizer in NMRI mice.
AB  - The octyltin stabilizer ZK 30.434 is a mixture of 80% dioctyltin
      diisooctylthioglycolate (DOTTG) and 20% of monooctyltin triisooctylthioglycolate
      (MOTTG) and is used as stabilizer for rigid polyvinylchloride (PVC) materials.
      One of the applications of such stabilized films is the packaging of foodstuffs.
      Exposure to humans occurs via migration of DOTTG/MOTTG from PVC materials. In the
      present study the developmental toxicity of DOTTG/MOTTG in NMRI mice was
      investigated. Dams were treated orally with doses of 20, 30, 45, 67, or 100
      mg/kg/day DOTTG/MOTTG from gestation day 6 through 17 (plug = day 1). Resorption
      rates were significantly increased and fetal weights significantly reduced in the
      study group at the 2 highest doses. External anomalies, such as bent forelimbs,
      cleft palate, and exencephaly were reported in the group treated with 100
      mg/kg/day DOTTG/MOTTG, with the 67-mg/kd dose also exhibiting a significant
      increase in cleft palate. Moreover, an increase in skeletal anomalies was
      reported in fetuses exposed to 100 mg/kg/day. The doses of 20, 30, and 45
      mg/kg/day elicited a significant increase in supernumerary lumbar ribs. It can be
      concluded that DOTTG/MOTTG is embryo-fetotoxic and induces developmental effects.
      The study revealed the need for the establishment of different No-Observed
      Adverse Effect Levels (NOAEL) for the endpoints investigated.

PMID- 11297872
TI  - The impact of calcium, magnesium, zinc, and copper in blood and seminal plasma on
      semen parameters in men.
AB  - To investigate the impact of calcium, magnesium, zinc, and copper in blood and
      seminal plasma on semen parameters, 107 fertile and 103 subfertile males provided
      a standardized blood and semen specimen. Total calcium and magnesium
      concentrations were determined with colorimetric end point assay procedures. Zinc
      and copper were determined by flame atomic absorption spectrophotometer (AAS).
      Semen analysis was performed according to World Health Organization guidelines
      (1992). The concentrations of calcium, magnesium, zinc, and copper in blood and
      seminal plasma were not different between the subfertile and fertile group. Weak
      correlations were demonstrated between blood plasma zinc concentrations and sperm
      count (rs = 0.18), sperm motility (rs = 0.15), and abnormal sperm morphology (rs
      = 0.13). Zinc and magnesium concentrations in seminal plasma correlated weakly
      with sperm count (rs = 0.17 and rs = 0.16, respectively), and copper
      concentrations in blood plasma with motility (rs = 0.25). Strong correlations
      were found between calcium, magnesium, and zinc in seminal plasma. Although
      calcium, magnesium, zinc, and copper play an essential role in spermatogenesis
      and fertility, the determination of these elements in blood and seminal plasma
      does not discriminate on the basis of fertility in this group of men.

PMID- 11297873
TI  - The psoralens adversely affect reproductive function in male wistar rats.
AB  - The psoralens occur naturally in produce and are widely used in skin therapy.
      Studies show that 5-methoxypsoralen and 8-methoxypsoralen reduced birth rates in
      rats. We determined the effect of psoralens on reproductive function in male
      rats. Male Wistar rats were dosed daily with 5-methoxypsoralen or 8
      methoxypsoralen (75 or 150 mg/kg, p.o.), or vehicle control. Treated males had
      significantly smaller pituitary glands, fewer sperm per ejaculate, and fewer
      sperm in the vasa defferentia and epididymides than controls. Dosing
      significantly elevated levels of testosterone and increased relative testis
      weight, but did not directly affect testicular weight. Females bred to dosed
      males required more time to become pregnant, and these males required more
      breeding attempts. The findings demonstrate the importance of determining the
      potential risk for infertility and/or birth defects in humans who are exposed to
      therapeutic, dietary, or occupational psoralens.

PMID- 11297874
TI  - Sperm and testicular modifications induced by subchronic treatments with vanadium
      (IV) in CD-1 mice.

PMID- 11297875
TI  - Two-generation reproduction studies in Rats fed di-isodecyl phthalate.
AB  - Di-isodecyl phthalate (DIDP) is a commercial plasticizer with low toxicity in
      many animal studies. The effects of dietary DIDP administration on fertility and
      developmental parameters were assessed in Sprague-Dawley rats utilizing two
      generation reproductive toxicity studies generally consistent with current
      regulatory guidelines. Dietary levels ranged from 0.02 to 0.8% (or approximately
      15 to 600 mg/kg/day). In the reproductive studies, there were no effects on
      fertility, but there were decreases in adult body weight along with corresponding
      increases in liver and kidney weights and histopathologic changes indicative of
      peroxisomal proliferation. There were no effects on live birth index, but reduced
      offspring survival was observed at postnatal days 1 to 4. This reduced survival
      was more pronounced in the F2 generation in which statistical significance was
      achieved at levels of 0.2% DIDP and greater. There were also transient decreases
      in offspring body weights prior to weaning, corresponding to rapid offspring
      growth, and high levels of food consumption. There were no notable alterations in
      developmental landmarks. Overall, these studies provided experimentally defined
      No-Observed-Adverse-Effect Levels (NOAELs) of 0.06% (approximately 50 mg/kg/day)
      for F2 offspring survival and 0.8% (approximately 600 mg/kg/day) for fertility,
      other measures of reproductive function, and developmental landmarks. Statistical
      evaluation of the data from both studies identified 108 mg/kg/day with a 95%
      lower bound value of 86 mg/kg/day as a theoretical NOAEL for reduced F2 offspring
      survival.

PMID- 11297876
TI  - Effect of mono-ethylhexyl phthalate on MA-10 Leydig tumor cells.
AB  - We examined the effect of mono-ethylhexyl phthalate (MEHP) on MA-10 Leydig tumor
      cell structure and function. Cells were exposed to various concentrations of MEHP
      for 24 h and then stimulated with saturating concentrations of hCG for 2.5 h.
      Progesterone production, cell viability, and protein content were moderately
      inhibited by low concentrations and severely inhibited by high concentrations of
      MEHP. Electron microscopy showed a variety of alterations in the MEHP-treated
      cells, increasing in severity with increasing concentrations of MEHP. Lipid
      droplets were profoundly affected in the cells treated with MEHP and morphologic
      evidence that metabolism of lipid storage droplets ceases at approximately the
      same time progesterone synthesis stops was seen. Morphometric studies indicated
      that the number of lipid droplets appeared to be increased 2.5-fold over control
      levels at MEHP concentrations of 10(-6) to 10(-3) M whereas mitochondrial volume
      fraction decreased. These results suggest that MEHP in Leydig cells may act as a
      mitochondrial toxicant and lipid metabolism disrupter.

PMID- 11297877
TI  - Adverse effects on development of the reproductive system in male offspring of
      rats given monobutyl phthalate, a metabolite of dibutyl phthalate, during late
      pregnancy.
AB  - The objective of this study was to determine the adverse effects of monobutyl
      phthalate (MBuP), a major metabolite of dibutyl phthalate (DBP), on development
      of the reproductive system in offspring following maternal administration during
      late pregnancy, and to assess the role of MBuP in the antiandrogenic effects of
      DBP. Pregnant rats were given MBuP by gastric intubation at 250, 500, or 750
      mg/kg on days 15 through 17 of pregnancy. Maternal body weight gain and food
      consumption during the administration period were significantly decreased at 500
      mg/kg and higher and at 750 mg/kg, respectively. A significant increase in the
      incidence of postimplantation embryonic loss was found at 500 mg/kg and higher.
      The body weights of male and female fetuses were significantly lower at 750
      mg/kg. A significant increase in the incidence of fetuses with undescended testes
      was found at 250 mg/kg and higher. A significant decrease in the anogenital
      distance (AGD) of male fetuses was observed at 250 mg/kg and higher. The AGD/body
      weight ratio and AGD/cube root of body weight ratio in male fetuses was also
      significantly reduced at 250 mg/kg and higher. The AGD, AGD/body weight ratio and
      AGD/cube root of body weight ratio in female fetuses in the MBuP-treated groups
      were comparable to those in the control group. The present study indicates that
      MBuP on days 15 to 17 of pregnancy produced adverse effects on the development of
      reproductive system in male offspring and suggest that MBuP may be responsible
      for the induction of the antiandrogenic effects of DBP.

PMID- 11297878
TI  - Reproductive toxicity of exemestane, an antitumoral aromatase inactivator, in
      rats and rabbits.
AB  - Exemestane is an orally active, irreversible inactivator of aromatase,
      structurally related to the natural substrate androstenedione, in clinical use at
      25 mg daily for the treatment of advanced breast cancer in postmenopausal women.
      The reproductive and developmental toxicity of exemestane was assessed in rats
      and rabbits with oral administration. Pivotal experiments included a fertility
      study (Segment I), in which female rats received exemestane doses of 4, 20, or
      100 mg/kg/day from two weeks premating until GD 20 (cesarean-sectioned dams), or
      until GD 15 and then from D 1 to D 21 postpartum (dams allowed to deliver), and
      developmental toxicity studies (Segment II), in which rats and rabbits were
      treated from GD 6 through GD 17 (rats) or GD 18 (rabbits) at doses of 10, 50,
      250, or 810 mg/kg/day and 30, 90, or 270 mg/kg/day, respectively. All rabbits and
      two-thirds of the rats were cesarean sectioned toward the end of pregnancy to
      determine litter parameters and examine structural abnormalities in the fetuses;
      the remaining one-third of the rats was allowed to litter and rear pups to
      weaning. No pivotal male fertility or peri- and postnatal studies were performed,
      taking into consideration the therapeutic use. Postnatal effects on the first
      generation offspring were assessed in both studies in rats, in the portion of
      dams allowed to deliver. Their F1 offspring were raised to adulthood, when they
      were evaluated for reproductive performance, and the F1 females were terminated
      on GD 20. The dosing schedule for the Segment I study in rats, which included a
      postnatal component, was established to exclude exposure before and during
      parturition (by withdrawing treatment from GD 16 until the end of parturition).
      This withdrawal of treatment was put in place because in a preliminary study with
      treatment including the peripartum period, doses from 5 to 200 mg/kg/day
      prolonged gestation and interfered with parturition.Overall, studies in rats
      showed that female fertility was not affected up to 100 mg/kg/day, but doses
      higher than 4 mg/kg/day, which is approximately the pharmacologically active dose
      (ED50 = 3.7 mg/kg), prolonged gestation and impaired parturition, leading to
      maternal deaths in labor and perinatal deaths of offspring. Rats killed on GD 20
      showed nondose-related increases in resorptions at doses higher than 10
      mg/kg/day, a reduction in fetal body weights at 20 and 100 mg/kg/day (fertility
      study) and 810 mg/kg/day (developmental toxicity study), and an increase in
      placental weights at all doses. Female fetuses exposed in utero until GD 20 at
      100 mg/kg/day showed an increase in the anogenital distance, very likely related
      to an increase of the potent androgen DHT as a consequence of aromatase
      inhibition. Morphologic examinations in fetuses and born pups that were exposed
      in utero up to the end of the organogenesis period, as well as postnatal
      investigations on offspring up to adulthood, showed no treatment-related effects.
      In a developmental toxicity study in rabbits, treatment at 270 mg/kg/day affected
      maternal food intake and body weight gain, caused abortion or total resorption in
      about 30% of pregnant females, and reduced body weight and numbers of live
      fetuses, but did not affect fetal morphology. It was concluded that exemestane
      did not affect parturition in rats at 4 mg/kg/day or pregnancy in rabbits at 90
      mg/kg/day (about 1.5 and 70 times the human dose, respectively, on a mg/m2 basis)
      and was not teratogenic in rats and rabbits. Exemestane is marketed for use only
      in postmenopausal women. Its labeling includes a contraindication to use in
      pregnant or lactating women.

PMID- 11297879
TI  - Effect of human chorionic gonadotrophin coadministration on the activities of
      ovarian Delta5-3beta-hydroxysteroid dehydrogenase, and 17beta-hydroxysteroid
      dehydrogenase, and ovarian and uterine histology in lithium chloride-treated
      albino rats.
AB  - Lithium chloride, a compound with clinical use in bipolar disorder, produces
      adverse effects on ovarian function in amphibian and rodent models. This study
      examined the effect of human chorionic gonadotrophin coadministration on ovarian
      steroidogenic and gametogenic activities in lithium chloride-treated rats.
      Relative ovarian and uterine weights, ovarian Delta(5)-3beta-hydroxysteroid
      dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities,
      folliculogenesis, uterine diameter, endometrial and myometrial thickness, and
      uterine luminal epithelial height were decreased significantly after lithium
      chloride treatment for 28 days at 1.6 mg/kg/day, the human therapeutic dose.
      These parameters were unchanged from the control level when subcutaneous (s.c.)
      human chorionic gonadotrophin (hCG) at 25 microg/kg/day was coadministered with
      the lithium chloride. The duration of the oestrous cycle was increased in lithium
      chloride-treated rat with longer metestrous and diestrous phases. Administration
      of hCG with lithium chloride prevented these estrous cycle alterations. We
      conclude that hCG can protect ovarian steroidogenic and gametogenic function
      after lithium chloride treatment.

PMID- 11297881
TI  - Reflections on the limitations to epidemiology.

PMID- 11297880
TI  - Effect of human chorionic gonadotrophin coadministration on ovarian steroidogenic
      and folliculogenic activities in cyclophosphamide treated albino rats.
AB  - Quantitative evaluation of ovarian Delta5,3beta- hydroxysteroid dehydrogenese
      (HSD) and 17beta - HSD activities along with radioimmunoassay of plasma levels of
      gonadotrophins (FSH and LH), and estradiol (E2), and quantification of different
      types of developing follicles and regressive follicles were noted in mature rats
      of the Wistar strain following treatment with cyclophosphamide at a dose of 5
      mg/kg body weight/day for 28 days. A significant reduction in plasma levels of LH
      and E2 along with significant diminution in the activities of ovarian
      Delta5,3beta -HSD and 17beta- HSD were observed following cyclophosphamide
      treatment for 28 days without any change in the plasma level of FSH. This
      treatment also produced a marked degree of degeneration in different types of
      follicles. Coadministration of hCG at 5 IU/kg body weight/day for 28 days in the
      cyclophosphamide-treated group provided significant protection except with
      respect to plasma LH. These results suggest the possibility of an indirect action
      of cyclophosphamide at the level of the ovary.

PMID- 11297882
TI  - The reviewer's task and the evolvement of epidemiologic research.

PMID- 11297883
TI  - Effects of using consumer and expert ratings of an activities of daily living
      scale on predicting functional outcomes of postacute care.
AB  - To test the effects of using preference weights for activities of daily living
      (ADL) outcome measures derived from different sources, data from a large study of
      the outcomes of postacute care (PAC study) were analyzed using two different
      weightings for the ADL measures. Both were developed using the same magnitude
      estimation technique; one from a panel of long-term care experts (the expert
      rating system); the other from a group of elderly Medicare beneficiaries (the
      consumer rating system). Neither group was directly involved in the PAC study.
      Although ADL scores generated by both rating systems were highly correlated prior
      to hospitalization and at hospital discharge, the consumer and expert rating
      systems generated significantly different functional outcomes measured by the
      change of ADL scores with a few exceptions. Compared to the consumer rating
      system, the expert rating system generated a greater change in functional
      outcomes at each of three follow-up time points after hospital discharge. This
      study suggests that the choice of weights for ADL items is important.

PMID- 11297884
TI  - Adjusting for multiple testing--when and how?
AB  - Multiplicity of data, hypotheses, and analyses is a common problem in biomedical
      and epidemiological research. Multiple testing theory provides a framework for
      defining and controlling appropriate error rates in order to protect against
      wrong conclusions. However, the corresponding multiple test procedures are
      underutilized in biomedical and epidemiological research. In this article, the
      existing multiple test procedures are summarized for the most important
      multiplicity situations. It is emphasized that adjustments for multiple testing
      are required in confirmatory studies whenever results from multiple tests have to
      be combined in one final conclusion and decision. In case of multiple
      significance tests a note on the error rate that will be controlled for is
      desirable.

PMID- 11297885
TI  - The association between socioeconomic status, health insurance coverage, and
      quality of life in men with prostate cancer.
AB  - The objective of this study was to examine the effect of socioeconomic status and
      insurance status on health-related quality of life (HRQOL) outcomes in men with
      prostate cancer. The design was a retrospective cohort study using multiple
      sites, including both academic and private practice settings. A cohort of 860 men
      with newly diagnosed, biopsy-proven prostate cancer of any stage was identified
      within CaPSURE, a longitudinal disease registry of prostate cancer patients.
      HRQOL was assessed with validated instruments, including the RAND 36-item Health
      Survey (SF-36) and the UCLA Prostate Cancer Index. Covariates included insurance
      status, education level, annual income, age, stage, comorbidity, Gleason grade,
      baseline PSA, marital status, ethnicity and primary treatment. HRQOL measurements
      were taken at 3-6-month intervals. Analysis of covariance was used to determine
      the effect of SES and insurance status on the HRQOL domains at baseline and over
      time. Patients with lower annual income had significantly lower baseline HRQOL
      scores in the all of the domains of the SF-36 and four of eight disease-specific
      HRQOL domains. No relationship was seen between annual income and HRQOL outcomes
      over time. Conversely, health insurance status was associated with HRQOL over
      time, but not at baseline. Health insurance status appears to have a unique
      effect on general HRQOL outcomes in men after treatment for prostate cancer. This
      study confirms the commonly held belief that patients of lower SES tend to have
      worse quality of life at baseline and following treatment for their disease.
      These findings have important ramifications for clinicians, researchers and
      policy makers.

PMID- 11297886
TI  - Racial differences in colorectal cancer mortality. The importance of stage and
      socioeconomic status.
AB  - This investigation studies racial and socioeconomic differences in mortality from
      colorectal cancer, and how they vary by stage and age at diagnosis. Cox
      proportional hazards models were used to estimate the hazard ratio of dying from
      colorectal cancer, controlling for tumor characteristics and sociodemographic
      factors. Black adults had a greater risk of death from colorectal cancer,
      especially in early stages. The gender gap in mortality is wider among blacks
      than whites. Differences in tumor characteristics and socioeconomic factors each
      accounted for approximately one third of the excess risk of death among blacks.
      Effects of socioeconomic factors and race varied significantly by age. Higher
      stage-specific mortality rates and more advanced stage at diagnosis both
      contribute to the higher case-fatality rates from colorectal cancer among black
      adults, only some of which is due to socioeconomic differences. Socioeconomic and
      racial factors have their most significant effects in different age groups.

PMID- 11297887
TI  - Indices of adipose tissue distribution, apolipoproteins B and AI, lipoprotein
      (a), and triglyceride concentration in children aged 4-11 years: the Third
      National Health and Nutrition Examination Survey.
AB  - This study examined the association of body fat distribution with serum
      apolipoproteins, lipoprotein (a), and triglyceride, risk factors for
      cardiovascular morbidity, in a representative sample of U.S. black, white, and
      Hispanic children. Data from the Third National Health and Nutrition Examination
      Survey for children aged 4-11 years revealed the mean waist-to-hip ratio (WHR)
      varied consistently with age, gender, and ethnic group. Levels were highest in
      Mexican Americans. WHR showed significant negative associations with apo AI
      concentration and positive associations with apo B and the ratio of apo B to apo
      AI independent of age but not body mass index (BMI). Associations of WHR with
      serum triglyceride concentration were independent of age and BMI. Other indices
      of body fat distribution were not superior to WHR. Lp (a) was not consistently
      associated with WHR. In conclusion, after controlling for BMI and age, body fat
      distribution was not significantly associated with apo AI and apo B with few
      exceptions. Nor was Lp (a) significantly associated with body fat distribution.
      Casual serum triglyceride levels were significantly positively associated with
      WHR independent of age and BMI in non-Hispanic white and Mexican American
      children.

PMID- 11297888
TI  - Validating recommendations for coronary angiography following acute myocardial
      infarction in the elderly: a matched analysis using propensity scores.
AB  - We determined whether adherence to recommendations for coronary angiography more
      than 12 h after symptom onset but prior to hospital discharge after acute
      myocardial infarction (AMI) resulted in better survival. Using propensity scores,
      we created a matched retrospective sample of 19,568 Medicare patients
      hospitalized with AMI during 1994-1995 in the United States. Twenty-nine percent,
      36%, and 34% of patients were judged necessary, appropriate, or uncertain,
      respectively, for angiography while 60% of those judged necessary received the
      procedure during the hospitalization. The 3-year survival benefit was largest for
      patients rated necessary [mean survival difference (95% CI): 17.6% (15.1, 20.1)]
      and smallest for those rated uncertain [8.8% (6.8, 10.7)]. Angiography
      recommendations appear to select patients who are likely to benefit from the
      procedure and the consequent interventions. Because of the magnitude of the
      benefit and of the number of patients involved, steps should be taken to
      replicate these findings.

PMID- 11297890
TI  - Reproductive risk factors of fetal asphyxia at delivery: a population based
      analysis.
AB  - To investigate reproductive maternal risk factors of intrapartum fetal asphyxia,
      we analyzed 556 women with singleton pregnancies complicated by intrapartum fetal
      asphyxia who gave birth at Kuopio University Hospital from January 1990 to
      December 1998. The general obstetric population (N=21746) was selected as the
      reference group and logistic regression analysis was used to identify independent
      reproductive risk factors. The incidence of intrapartum fetal asphyxia was 2.5%.
      Placental abruption, primiparity, alcohol use during pregnancy, low birth weight,
      preeclampsia, male fetuses, and small-for-gestational age births were independent
      risk factors of intrapartum asphyxia, with adjusted relative risks of 3.74, 3.10,
      1.75, 1.57, 1.49, 1.48 and 1.33, respectively. Most cases of intrapartum fetal
      asphyxia occur in low-risk pregnancies and, therefore, risk screening in
      antenatal care cannot accurately predict which women will eventually need
      emergency care for fetal asphyxia.

PMID- 11297889
TI  - The effect of gender on the relationship between body fat distribution and lung
      function.
AB  - Although abdominal obesity, as measured by waist-to-hip ratio (WHR), has long
      been recognized as a risk factor for metabolic and cardiovascular diseases,
      little is known about the effect of WHR on pulmonary function, especially in
      women. In this study of 1094 men and 540 women (18-102 years) from the Baltimore
      Longitudinal Study of Aging (BLSA), we examined the effect of WHR on forced
      expiratory volume in 1 s (FEV(1)). Cross-sectional analyses, after accounting for
      body mass index (BMI) and other variables, showed a strong inverse association of
      WHR with FEV(1) in men (beta = -1.338, P=.0001) but not in women. Furthermore,
      larger values of WHR were associated with greater reductions of forced vital
      capacity (FVC) in men (beta = -1.383, P =.0005) compared to women (beta = -0.679,
      P =.02). Thus, body fat distribution has independent effects on lung function
      that are more prominent in men than women.

PMID- 11297891
TI  - A population-based study of familial soft tissue tumors.
AB  - We used the nationwide Swedish Family-Cancer Database to analyze the risk for
      soft tissue tumors in offspring by parental cancers and in siblings of soft
      tissue tumor probands. Additionally, risk for second cancer following soft tissue
      tumor was investigated. In offspring, 1488 soft tissue tumors were diagnosed
      between years 1958 and 1996. Groups of offspring were compared by calculating
      standardized incidence ratios (SIRs) for soft tissue tumors. Parental breast,
      prostate and connective tissue cancers were associated with offspring soft tissue
      tumors in sex- and age-specific groups. The SIRs were of borderline significance,
      suggesting a small etiological contribution by Li-Fraumeni syndrome. Soft tissue
      tumors conveyed a high risk of second soft tissue tumor, probably partially due
      to recurrences. However, the observed risk for second nervous system cancer was
      consistent with Li-Fraumeni syndrome. Other associations were unlikely to be due
      to Li-Fraumeni or other known syndromes, but they could be spurious findings
      arising from multiple comparisons. Among these, parental stomach cancer (SIR
      3.19, 95% CI 1.69-5.17) and endocrine gland tumors (SIR 3.66, 95% CI 1.32-7.17),
      particularly parathyroid tumors (SIR 4.46, 95% CI 1.41-9.23), were associated
      with offspring fibrosarcoma, and parental breast cancers with offspring
      leiomyosarcoma (SIR 2.04, 95% CI 1.08-3.30).

PMID- 11297892
TI  - Bone mineral density and breast cancer risk in postmenopausal women.
AB  - Two recent studies have shown a woman's bone mineral density (BMD) (a composite
      measure of exposure to many different factors throughout one's lifetime) predicts
      breast cancer. In a prospective cohort study, we examined whether hip BMD was
      associated with breast cancer risk among 8203 postmenopausal women. During an
      average follow-up of 3.7 years, 131 incident breast cancer cases (102 invasive)
      were identified. Cox proportional hazards models were used to obtain estimates of
      the relative risk of breast cancer. Our results demonstrate an increase in breast
      cancer risk among women with higher BMD. Independent of age, geographic area, and
      body mass index, relative to the lowest BMD quartile the risk of breast cancer
      (95% confidence interval) by increasing quartile was 1.9 (1.1, 3.2), 1.5 (0.8,
      2.6), and 1.5 (0.8, 2.7), respectively. An examination of other factors important
      in determining BMD may help explain the positive association between BMD and
      breast cancer.

PMID- 11297893
TI  - Fiber intake, constipation, and risk of varicose veins in the general population:
      Edinburgh Vein Study.
AB  - The purpose of the present study was to determine the relationship between fiber
      intake, constipation, and clinical venous disease in the general population. The
      Edinburgh Vein Study was comprised of 1566 men and women aged 18-64 years who
      were selected at random from the age-sex registers of 12 general practices. Fiber
      intake, intestinal transit time, defecation frequency and the prevalence of
      straining at stool were all found to be significantly different between the
      sexes. Men who reported that they strained to start passing a motion showed a
      higher prevalence of mild and severe trunk varices compared to men who did not
      strain. After adjustment for social class, BMI and mobility at work, this group
      of men showed a significantly elevated risk of having severe trunk varices (OR
      2.76, 95% CI 1.16, 6.58). In contrast, no consistent relationships were seen
      among women. Overall, within this Western general population, an association
      between dietary fiber, constipation and the presence or severity of varicose
      veins was not supported.

PMID- 11297894
TI  - A mail survey of United States hematologists and oncologists: a comparison of
      business reply versus stamped return envelopes.
AB  - Mailed surveys are a popular means of obtaining data on large populations. In
      July 1999 a mail survey was conducted among 3000 randomly selected members of the
      American Society of Hematology to assess their approach to diagnosis and
      treatment of polycythemia vera. Because the researchers and the study population
      are members of the same professional organization with a vested interest in the
      results, we anticipated that the advantages of return stamped postage seen in
      previous studies would be less significant. The response rate for stamped return
      envelopes was 38% versus 32% for business reply envelopes. This statistically
      significant difference (P =.0005) of six percentage points is comparable to
      previous research. Excluding labor, the total cost per returned survey was $2.62
      for business reply envelopes versus $1.82 for stamped return envelopes. We
      conclude that stamped return envelopes are a more effective and cost-efficient
      means of procuring data from physician specialists.

PMID- 11297895
TI  - Role of modelling and simulation in Phase I drug development.
AB  - Although the use of pharmacokinetic/pharmacodynamic modelling and simulation
      (M&S) in drug development has increased during the last decade, this has most
      notably occurred in patient studies using the population approach. The role of
      M&S in Phase I, although of longer history, does not presently have the same
      impact on drug development. However, trends such as the increased use of
      biomarkers and clinical trial simulation as well as adoption of the learn/confirm
      concept can be expected to increase the importance of modelling in Phase I. To
      help identify the role of M&S, its main advantages and the obstacles to its
      rational use, an expert meeting was organised by COST B15 in Brussels, January 10
      11, 2000. This article presents the views expressed at that meeting. Although it
      is clear that M&S occurs in only a minority of Phase I clinical trials, it is
      used for a large number of different purposes. In particular, M&S is considered
      valuable in the following situations: censoring because of assay limitation,
      characterisation of non-linearity, estimating exposure-response relationship,
      combined analyses, sparse sampling studies, special population studies,
      integrating PK/PD knowledge for decision making, simulation of Phase II trials,
      predicting multiple dose profile from single dose, bridging studies and
      formulation development. One or more of the following characteristics of M&S
      activities are often present and severely impede its successful integration into
      clinical drug development: lack of trained personnel, lack of protocol and/or
      analysis plan, absence of pre-specified objectives, no timelines or budget, low
      priority, inadequate reporting, no quality assurance of the modelling process and
      no evaluation of cost-benefit. The early clinical drug development phase is
      changing and if these implementation aspects can be appropriately addressed, M&S
      can fulfill an important role in reshaping the early trials by more effective
      extraction of information from studies, better integration of knowledge across
      studies and more precise predictions of trial outcome, thereby allowing more
      informed decision making.

PMID- 11297896
TI  - Modeling and comparison of dissolution profiles.
AB  - Over recent years, drug release/dissolution from solid pharmaceutical dosage
      forms has been the subject of intense and profitable scientific developments.
      Whenever a new solid dosage form is developed or produced, it is necessary to
      ensure that drug dissolution occurs in an appropriate manner. The pharmaceutical
      industry and the registration authorities do focus, nowadays, on drug dissolution
      studies. The quantitative analysis of the values obtained in dissolution/release
      tests is easier when mathematical formulas that express the dissolution results
      as a function of some of the dosage forms characteristics are used. In some
      cases, these mathematic models are derived from the theoretical analysis of the
      occurring process. In most of the cases the theoretical concept does not exist
      and some empirical equations have proved to be more appropriate. Drug dissolution
      from solid dosage forms has been described by kinetic models in which the
      dissolved amount of drug (Q) is a function of the test time, t or Q=f(t). Some
      analytical definitions of the Q(t) function are commonly used, such as zero
      order, first order, Hixson-Crowell, Weibull, Higuchi, Baker-Lonsdale, Korsmeyer
      Peppas and Hopfenberg models. Other release parameters, such as dissolution time
      (tx%), assay time (tx min), dissolution efficacy (ED), difference factor (f1),
      similarity factor (f2) and Rescigno index (xi1 and xi2) can be used to
      characterize drug dissolution/release profiles.

PMID- 11297897
TI  - The effect of hydrogen bonding on diffusion across model membranes: consideration
      of the number of H-bonding groups.
AB  - The diffusion of a series of phenols across simple silicone membranes impregnated
      with either octanol or toluene was studied. These solvents are taken up and
      saturate the membrane. The presence of the solvents in a solid membrane allows
      them to interact with any permeant that cross the membrane. This membrane was
      used to simulate a bio-membrane, e.g. the skin, capable of hydrogen bonding with
      the permeant. As the number of H-bonding groups was increased the flux across
      both the octanol and toluene impregnated membranes decreased. However,
      deconvolution of the data showed that for the octanol impregnated membrane the
      diffusion coefficient (Dm) decreased significantly with the number of H-bonding
      groups. This was not the case for the toluene impregnated membrane. Furthermore
      the spatial configuration of the -OH groups around the aromatic ring had a
      significant effect on the decrease in Dm. These findings have considerable
      implications in understanding the absorption of permeants across bio-membranes
      capable of H-bonding.

PMID- 11297898
TI  - Characterization of microcrystalline cellulose and silicified microcrystalline
      cellulose wet masses using a powder rheometer.
AB  - A powder rheometer has been used to study the properties of wet powder masses and
      the results have been compared to the mixer torque rheometer (MTR). Two different
      microcrystalline cellulose (MCC) grades (Avicel and Emcocel) and silicified
      microcrystalline cellulose (SMCC, Prosolv) were used as model powders. The wet
      massing behaviour of one material (Prosolv) was studied by the powder rheometer
      using liquid addition experiments, while the rheological properties of wet
      granules were studied using both the powder rheometer and the MTR. In water
      addition measurements the torque behaved in a similar way to MTR measurements and
      the maximum value of ZTL (zero torque limit) was achieved at the capillary state
      of wet mass. The wet granules exhibited different behaviour in the powder
      rheometer and the MTR experiments, which indicates that these rheometers involve
      different shear forces or they measure different properties of the wet granules.
      Emcocel wet masses achieved the capillary state at lower liquid amount than
      Avicel and Prosolv masses, which indicates that Emcocel is not able to hold as
      much water in the internal structure as Avicel and Prosolv. The powder rheometer
      proved to be a sensitive piece of equipment, which can be used to study both dry
      and wet powder masses. It was able to distinguish wet granules from wet powder
      masses after liquid addition, whereas the MTR could not. However, before the
      powder rheometer can be properly utilised in wet powder mass studies, the problem
      of torque overload requires resolution.

PMID- 11297899
TI  - Estimation of rhG-CSF absorption kinetics after subcutaneous administration using
      a modified Wagner-Nelson method with a nonlinear elimination model.
AB  - The clearance of recombinant human granulocyte-colony stimulating factor (rhG
      CSF) is known to decrease with dose increase, and to be saturable. The average
      clearance after intravenous administration will be lower than that after
      subcutaneous administration. Therefore, the apparent absolute bioavailability
      with subcutaneous administration calculated from the AUC ratio is expected to be
      an underestimate. The absorption pharmacokinetics after subcutaneous
      administration was examined using the results of the bioequivalency study between
      two rhG-CSF formulations with a dose of 2 microg/kg. The analysis was performed
      using a modified Wagner-Nelson method with the nonlinear elimination model. The
      apparent absolute bioavailability for subcutaneous administration was 56.9 and
      67.5% for each formulation, and the ratio between them was approximately 120%.
      The true absolute bioavailability was, however, estimated to be 89.8 and 96.9%,
      respectively, and the ratio was approximately 108%. The absorption pattern was
      applied to other doses, and the predicted clearance values for subcutaneous and
      intravenous administrations were then similar to the values for several doses
      reported in the literature. The underestimation of bioavailability was around
      30%, and the amplification of difference was 2.5 times, from 8 to 20%, because of
      the nonlinear pharmacokinetics. The neutrophil increases for each formulation
      were identical, despite the different bioavailabilities. The reason for this is
      probably that the amount eliminated through the saturable process, which might
      indicate the amount consumed by the G-CSF receptor, was identical for each
      formulation.

PMID- 11297900
TI  - Synthesis of iron-crosslinked chitosan succinate and iron-crosslinked
      hydroxamated chitosan succinate and their in vitro evaluation as potential matrix
      materials for oral theophylline sustained-release beads.
AB  - Chitosan succinate (CS) and hydroxamated chitosan succinate (HCS) were prepared.
      The generated semisynthetic polymers were employed in the formation of drug
      loaded, iron(III)-crosslinked polymeric beads. Infrared spectroscopy was employed
      to prove the crosslinking. The produced beads were evaluated in vitro as drug
      prolonging and potentially orally administered delivery system. Theophylline was
      used as the loaded model drug. The generated beads proved to be successful in
      prolonging drug release. Iron leaching from the generated beads was minimal
      (<2%), and it only took place under acidic conditions (pH 1).

PMID- 11297901
TI  - A comparative study of an in situ adapted diffusion cell and an in vitro Franz
      diffusion cell method for transdermal absorption of doxylamine.
AB  - In order to determine whether a drug shows the potential for percutaneous
      absorption, both in situ and in vitro studies are used. In vitro studies are good
      indicators of transdermal drug delivery, but the possibility exists that
      anatomical changes in excised skin can influence drug delivery. The aim of this
      study was to compare the in vitro Franz diffusion cell method with an in situ
      adapted diffusion cell method. A saturated aqueous solution of doxylamine
      succinate was used as model drug and the receptor phase was an isotonic Sorensen
      buffered solution. The in vitro permeation studies were conducted using vertical
      Franz diffusion cells with nude mice skin. For in situ studies, a diffusion cell
      was implanted under the dorsal skin of a nude mouse, simulating the in vitro
      method. Both in situ and in vitro experiments were conducted over a period of 12
      h during which samples were collected every 90 min. The mean steady-state flux
      from Franz diffusion cells was 0.164+/-0.045 microg/cm2/h and flux determined by
      the in situ method was 0.113+/-0.034 microg/cm2/h. A statistical significant
      difference existed between the permeation results of the in vitro and in situ
      experimental methods. A subjective, semi-quantitative assessment of histological
      changes to excised nude mouse skin was done using light microscopy. This showed
      that excised skin undergoes sub-lethal injury (necrosis) during in vitro
      experiments, which may lead to increased permeability of the drug. It was noticed
      that in vitro and in situ permeation results showed very close correlation until
      approximately 4.5 h after commencement of experiments, after which, the
      permeation through excised skin increased. It was assumed that cell necrosis
      occurred to such an extent after approximately 4.5 h, that the barrier function
      of the stratum corneum decreased and permeation of the drug increased.

PMID- 11297902
TI  - Evaluation of gelatin microspheres for nasal and intramuscular administrations of
      salmon calcitonin.
AB  - The suitability of gelatin microspheres for nasal and intramuscular delivery of
      salmon calcitonin (sCT) was examined. Negatively and positively charged gelatin
      microspheres were prepared using acidic gelatin [isoelectric point (IEP) value of
      5.0] and basic gelatin (IEP=9.0), respectively. The average diameters of
      positively charged gelatin microspheres in their dried state were 3.4, 11.2, 22.5
      and 71.5 microm, while that of negatively charged gelatin microspheres was 10.9
      microm. Both types of gelatin microspheres were capable of adhering to the nasal
      mucosa. The mucoadhesion of positively charged gelatin microspheres was
      significantly higher than that of their negatively charged counterparts. The
      absorption of sCT after intranasal and intramuscular administration was evaluated
      by calculating the area above the hypocalcemic-time curve (AAC) in rats. The AAC
      values after nasal administration of sCT in positively and negatively charged
      gelatin microspheres were significantly greater than that in pH 7.0 PBS.
      Therefore, the nasal absorption of sCT was enhanced by both types of gelatin
      microspheres. The hypocalcemic effect after administration of sCT in positively
      charged gelatin microspheres of 11.2 microm was significantly greater than that
      of negatively charged gelatin microspheres of the same size. On the other hand,
      AAC values were not affected by their particle sizes. The AAC values after the
      intramuscular administration of sCT in positively and negatively charged gelatin
      microspheres were significantly increased compared to that in PBS. Furthermore,
      the time-courses of the plasma calcium levels differed between positively and
      negatively charged gelatin microspheres. The hypocalcemic effect of the
      negatively charged gelatin microspheres tended to appear more slowly and last
      longer compared to that of positively charged gelatin microspheres. The
      hypocalcemic effects after intramuscular administration of sCT in gelatin
      microspheres were not affected by their particle sizes as well as those after
      intranasal administration. In conclusion, the gelatin microspheres have been
      shown to be a useful vehicle for nasal or intramuscular delivery of sCT.

PMID- 11297903
TI  - The influence of polyvinylpyrrolidone on naproxen complexation with hydroxypropyl
      beta-cyclodextrin.
AB  - The combined effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) and
      polyvinylpyrrolidone (PVP) on the solubility of naproxen (NAP) was studied. Phase
      solubility analysis at different temperatures was used to investigate
      interactions in aqueous solution between NAP and the carriers, either alone or in
      combination. Equimolar NAP-HPbetaCD solid systems, in the presence or the absence
      of 15% (w/w) PVP, were prepared by cogrinding, kneading, coevaporation or freeze
      drying, and characterized by differential scanning calorimetry, X-ray powder
      diffraction analysis, infrared spectroscopy and dissolution rates. The combined
      use of PVP and HPbetaCD resulted in a synergistic increasing effect of the
      aqueous solubility of NAP (120 times that of the pure drug). The phenomenon was
      interpreted in terms of the strongest complexation capacity of HPbetaCD towards
      NAP, which was reflected by an about 65% increase in the apparent stability
      constant of the NAP-HPbetaCD complex in the presence of only 0.1% (w/v) PVP.
      Variations in thermodynamic parameters accounted for a PVP role in the formation
      of a NAP-HPbetaCD-PVP ternary complex. The positive effect of PVP also reflected
      on NAP dissolution rates from solid preparations, because all ternary systems,
      with the exception of physical mixtures, dissolved faster than the corresponding
      NAP-HPbetaCD binary systems. The results of solid state studies accounted for the
      occurrence of mechanically- and/or thermally-induced stronger interactions in
      ternary than in binary systems, that in some cases led to a complete loss of NAP
      crystallinity.

PMID- 11297904
TI  - Pharmacokinetic aspects of chloroquine-induced pruritus: influence of dose and
      evidence for varied extent of metabolism of the drug.
AB  - The significance of a pharmacokinetics basis in chloroquine (CQ)-induced pruritus
      was investigated by determining the disposition of the drug in two groups of
      volunteers; pruritus positive and pruritus negative. Single oral dose of 600 mg
      CQ was administered to each of 36 volunteers, 18 for each of the two groups.
      After a washout period of 9 months, 150 mg single oral dose of the drug was given
      to 12 of the same volunteers, six each from the two groups. Blood and urine
      samples were collected at predetermined times following administration of each
      dose. Concentrations of CQ and its major metabolite, desethylchloroquine (CQM),
      were measured in plasma and urine using an established HPLC method. Results
      showed that the ratio, AUC (CQ)/AUC (CQM), as well as AUC(0-48 h) and 24-h
      urinary CQ excretion were all significantly higher (P<0.05) in pruritus-positive
      compared to pruritus-negative volunteers, following administration of the 600-mg
      CQ dose. Also, urinary drug-metabolite ratios monitored over 0-48 h postdose were
      markedly higher in the pruritus positive group. However, after administration of
      the 150-mg dose, 24-h urinary CQ collection and urinary drug-metabolite ratios
      were highly comparable between the two groups (P>0.1). This study indicates that
      there might be a decreased metabolism of CQ in subjects susceptible to CQ-induced
      pruritus following ingestion of a therapeutic dose. It also suggests that the
      extent of metabolism of CQ in this group may be influenced by the dose of the
      drug. Comparatively higher CQ levels in pruritus susceptible subjects may
      possibly be responsible for the pruritus experienced by such individuals when
      given therapeutic regimen.

PMID- 11297905
TI  - P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface
      plasmon resonance biosensor screening assays.
AB  - The commonly used HIV-1 protease assays rely on measurements of the effect of
      inhibitions on the hydrolysis rate of synthetic peptides. Recently an assay based
      on surface plasmon resonance (SPR) was introduced. We have taken advantage of the
      fact that the SPR signal is proportional to the mass of the analyte interacting
      with the immobilised molecule and developed two new improved efficient
      competition assay methods. Thus, high molecular weight binders were used as
      amplifiers of the surface plasmon resonance signal. Linkers were attached by a
      Heck reaction to the para-positions of the P1/P1' benzyloxy groups of a linear C2
      symmetric C-terminal duplicated inhibitor to enable (a) biotin labelling or (b)
      direct immobilisation of the inhibitor to the biosensor surface matrix. The
      interaction properties of a series of 17 structurally diverse inhibitors was
      assessed and compared to previously reported data. The most sensitive assay was
      obtained by immobilising the enzyme and amplifying the signal with an antibody,
      giving a detection range between 0.1 nM and 10 microM. Immobilisation of the
      inhibitor resulted in a stable and durable surface but a narrower detection range
      (1-100 nM). The two competition assays are anticipated to be very suitable for
      fast screening of potential HIV inhibitors.

PMID- 11297906
TI  - Interaction between indomethacin and heavy metal ions in aqueous solution.
AB  - The interaction between indomethacin anions and heavy metal ions, such as
      cadmium, zinc and copper(II) ions, was studied in aqueous solution by
      polarographic techniques. Indomethacin anions form complexes with these heavy
      metal ions: the complex formed with cadmium ions is sparingly soluble, while more
      soluble and also stronger complexes are formed with zinc and copper(II). At high
      concentrations, where indomethacin anions undergo self-aggregation, these last
      compounds are solubilised. This property is briefly discussed and compared to
      that of bile salts. In the presence of calcium ions, indomethacin forms a poorly
      soluble salt and no evidence was detected for the formation of complex species.

PMID- 11297907
TI  - The changes in surface energetics with relative humidity of carbamazepine and
      paracetamol as measured by inverse gas chromatography.
AB  - The surface energetic parameters of carbamazepine and paracetamol have been
      studied using inverse gas chromatography modified to produce dry and ambient
      conditions within the column. The values of the dispersive component of the
      surface free energy (gamma(S)D) do not change significantly at the increased
      relative humidity. In contrast the specific component of the free energy of
      adsorption (-DeltaG(A)SP) as measured by polar probes, can either remain constant
      or decrease by up to 10%, depending on the material and the probe. This indicates
      that an increase in the relative humidity causes a decrease in the surface
      energetics of the powder surface. It is proposed that where the water molecules
      are adsorbing to the same sites as the polar probes, the interaction of these
      probes with the surface is decreased. To identify these sites, the preferential
      interaction of each probe, including water, with the drug molecule has been
      modelled.

PMID- 11297908
TI  - Scopolamine nasal spray in motion sickness: a randomised, controlled, and
      crossover study for the comparison of two scopolamine nasal sprays with oral
      dimenhydrinate and placebo.
AB  - Scopolamine has been used successfully for treatment of motion sickness for
      almost a century and the nasal administration was first studied 50 years ago.
      However, there never appeared a nasal dosage form. Finally, after finding a
      stable and suitable formulation for scopolamine, a study to investigate efficacy,
      safety, and tolerability was conducted, with a randomised, double-blind, double
      dummy, crossover, Latin square design including placebo control and a
      placebo/placebo control for internal validity at the German Air Force Institute
      of Aviation Medicine. To assess the efficacy of a new, stable and well-tolerated
      formulation of scopolamine nasal spray the reproducible induction of whole body
      vibrations by a rotating chair was chosen and a validated seasickness score
      (SKS). The reduction of SKS showed that scopolamine nasal spray at a
      concentration of 0.2% was statistically superior to both placebo and
      dimenhydrinate (P=0.003 and 0.004, respectively). There were no signs for a nasal
      or epipharyngeal irritation of the mucous membrane. Scopolamine nasal spray was
      found to be an effective and safe treatment in motion sickness, with a fast onset
      of action within 30 min after administration.

PMID- 11297909
TI  - Management of oral anticoagulants in the treatment of venous thromboembolism.
AB  - Venous thromboembolism still represents a major public health problem. After
      initial heparin therapy, oral anticoagulants are the treatment most often used.
      Bleeding is the major risk of such a therapy. This review of the literature
      emphasises the practical aspects of the clinical management of oral anticoagulant
      therapy, such as initiation, monitoring, interaction, withdrawal, optimal
      duration, bleeding complications and non-haemorrhagic adverse reactions.

PMID- 11297910
TI  - Renal function and renal disease in the elderly: Part I.
AB  - In all industrialized countries, life expectancy has risen in the past 100 years.
      The incidence of elderly patients reaching end-stage renal disease (ESRD) and
      requiring renal replacement therapy has also increased. During the past few
      decades, the pattern of ESRD has changed significantly with the emerging
      predominance of elderly patients. The causes of this phenomenon are manifold and
      include an increasing number of chronic diseases typical of the 'third age', such
      as type 2 diabetes mellitus and vascular disease. In many species, a consequence
      of aging includes deterioration of renal function, partly due to structural
      alterations, and partly as the result of a diminishing blood flow. In humans, the
      aging kidney is characterized by modifications resulting from organic and
      functional disturbances. In particular, type 2 diabetes mellitus has emerged as
      an important condition, the microvascular and macrovascular complications of
      which are a common cause of morbidity and mortality in older patients. In part I
      of this review, the morphological and functional changes of the aging kidney will
      be reviewed, as well as the pathological conditions leading to the loss of renal
      function in the elderly.

PMID- 11297911
TI  - Acute terminal ileitis, yersiniosis, and Crohn's disease: a long-term follow-up
      study of the relationships.
AB  - Background: During the past decade, very little has been published on the
      relationships between Yersinia enterocolitica, acute terminal ileitis (ATI), and
      Crohn's disease, possibly due to a decrease in Yersinia infections and,
      consequently, in ATI. Methods: Fifty-three patients admitted to Herlev University
      Hospital during the period 1976-1998 were diagnosed as having ATI while
      undergoing surgery for suspected acute appendicitis. The patients were followed
      up, and both Yersinia titers and the development of Crohn's disease were
      registered. Results: Forty-four patients (83%) were tested for Yersinia, 17 of
      whom (39%; 95% confidence limits, 24-55%) were positive. The incidence of
      yersiniosis in ATI decreased significantly during the observation period
      (P<0.05), whereas the incidence of ATI itself was unchanged. Thirteen of the 53
      patients (25%; 95% confidence limits, 14-38%) had, in addition to ATI, an
      inflamed appendix. Three patients developed Crohn's disease during a median
      observation period of 13 years (cumulative risk 6.1%). None of them had
      yersiniosis. Conclusions: The incidence of ATI remained stable during the
      observation period, even though the number of Yersinia infections decreased. This
      may have been due to an increase in gastrointestinal infections caused by other
      enteric pathogens. In accordance with previous findings, ATI patients who
      developed Crohn's disease did not have yersiniosis. Thus, it is still of
      prognostic value to test patients with ATI for Yersinia and perhaps for other
      enteric pathogens as well.

PMID- 11297912
TI  - Self-rated health and clinical status after PTCA: results of a 4-year follow-up
      in 500 patients.
AB  - Background: Data on the clinical long-term outcome of patients with coronary
      artery disease in the years following percutaneous interventions are rare. We
      therefore decided to conduct a study to: (1) analyze the efficiency of a
      retrospective inquiry using a questionnaire and (2) perform a clinical long-term
      follow-up of our patients. Methods and results: Some 45+/-7 months after PTCA, a
      questionnaire was sent to 549 patients who had been treated at our institution
      from July 1, 1989, to June 30, 1991. The response rate was 91.1%, with 49
      patients (8.9%) lost to follow-up. A total of 115/500 patients (23%) had
      reinterventions due to severe angina (69 patients (13.8%) undergoing re-PTCA and
      46 (9.2%) CABG). Sixteen patients (3.2%) had a myocardial infarction and 35
      patients (7.0%) died. Multivariate analysis revealed that patients who were
      asymptomatic 3 months after PTCA were likely to have a good long-term outcome.
      This was not found when comparing the clinical status immediately after PTCA to
      follow-up. Medical therapy with beta-blockers/aspirin/lipid-lowering drugs
      decreased from 75.2/82.2/35.4% at hospital discharge to 54.6/76.7/25.2% at follow
      up. Conclusions: The present study provided important quality data for our
      institution. The response rate to the questionnaire was surprisingly high
      (91.1%), indicating that retrospective inquiries may also be efficient. The rate
      of reinterventions during long-term follow-up (23%) was acceptably low. Good self
      rated health 3 months after the intervention turned out to be a strong predictor
      for a good clinical long-term outcome. Furthermore, we observed an underuse of
      cardiac medication, something that will be the subject of further quality
      improvement measures.

PMID- 11297913
TI  - Selective mobilisation of fatty acids from human adipose tissue.
AB  - Background: Adipose tissue is a storage organ for dietary fat. During fasting,
      fatty acids are released into serum as free fatty acids (FFA). Experimental
      studies indicate that fatty acids are selectively mobilised from adipose tissue
      into serum. The aim of this study was to investigate whether the composition of
      the serum FFA fraction reflects selective mobilisation in the fasting state in
      humans. Methods: The fatty acid composition of fasting serum FFA and adipose
      tissue were analysed from 112 patients with myocardial infarction and 107 healthy
      control subjects using gas-liquid chromatography. The subjects' habitual diet was
      analysed using a food-frequency questionnaire. Results: Significant correlations
      were found between serum FFA and adipose tissue, particularly for the percentage
      content of linoleic acid (r=0.73), eicosapentaenoic acid (r=0.68), alpha
      linolenic acid (r=0.67) and palmitoleic acid (r=0.60). Percentage contents of
      palmitic, stearic, linoleic, alpha-linolenic, eicosapentaenoic and
      docosahexaenoic acid were higher in serum FFA than in adipose tissue, whereas
      oleic and palmitoleic acid were relatively more abundant in adipose tissue. This
      may indicate that the former group of fatty acids is preferentially mobilised
      from adipose tissue into serum. High correlations for polyunsaturated fatty acids
      were observed between percentage contents of dietary and adipose tissue fatty
      acids. The correlation of fatty acids between diet and serum FFA was weak, but a
      tendency towards higher correlations for polyunsaturated fatty acids was
      observed. Conclusions: Our findings are compatible with the hypothesis that, in
      the fasting state, fatty acids are selectively mobilised from adipose tissue into
      serum FFA.

PMID- 11297914
TI  - Antioxidant liposoluble vitamins and carotenoids in chronic hepatitis.
AB  - Background: It is known that antioxidant liposoluble vitamins and carotenoids are
      reduced in liver cirrhosis, but little is known about chronic viral hepatitis,
      where oxidative damage has to be taken into account. Methods: Fifty-five patients
      with chronic hepatitis, mainly C virus-related, were matched with 16 patients
      with biliary stones and 20 healthy controls. Plasma and liver analyses were
      carried out using a well-tried HPLC technique that affords an accurate
      quantification of retinol, tocopherol, alpha- and beta-carotene, cryptoxanthin,
      and lycopene. Results: Plasma concentration of retinol, tocopherol, beta
      carotene, and lycopene was significantly decreased in both patient groups,
      particularly in those with chronic hepatitis. In contrast, liver concentration of
      both esterified and free retinol, tocopherol, and some carotenoids was better
      preserved in the hepatitis group than in the cholelithiasis group. A strict
      correspondence between aminotransferases and the amount of liver-stored retinol
      was documented. Conclusions: Plasma vitamin and carotenoid depletion co-existing
      with preserved liver storage may indicate a functional defect in liver pool
      mobilization or even a real depletion of the antioxidant defenses, which play a
      key role in averting cellular damage. The implications for nutrition and therapy
      need to be taken into account.

PMID- 11297915
TI  - The outcome of esophagogastroduodenoscopy (EGD) in asymptomatic outpatients with
      iron deficiency anemia after a negative colonoscopy.
AB  - Background: Both iron deficiency and iron deficiency anemia require extensive
      investigation because of their possible association with gastrointestinal
      malignancy. If no other sources of blood loss are apparent, the gastrointestinal
      tract is examined to detect sources of occult blood loss. In the absence of
      gastrointestinal symptoms, the colon is first examined, especially in the
      elderly. The aim of this study was to determine the outcome of
      esophagogastroduodenoscopy (EGD) after a prior negative colonoscopy in
      outpatients without gastrointestinal complaints, referred due to iron deficiency
      anemia. Methods: Thirty-five patients (22 female and 13 male) with a median age
      of 71 years were studied over a 2-year period. Anemia was defined as a hemoglobin
      (Hb) level below 7.4 mmol/l in women or below 8.0 mmol/l in men and iron
      deficiency if one of the following was present: ferritin level equal to or below
      20 ug/l for men and equal to or below 10 ug/l for women, a serum iron
      concentration equal to or below 45 ug/dl (8.1 umol/l) with a transferrin
      saturation of 10% or less, or the absence of iron stores in bone marrow biopsy
      specimens. Patients with prior gastrointestinal disease or surgery,
      gastrointestinal symptoms, or other obvious causes of blood loss were excluded.
      Lesions that were considered to be potential sources of blood loss were clearly
      defined. Results: The mean Hb level of the 35 patients studied was 5.5 mmol/l
      (range 1.8-7.8 mmol/l). Abnormalities were found in 10 patients (28.6%), all of
      which were benign. Erosive and ulcerative lesions in the stomach, in a hiatal
      hernia, or in the esophagus were diagnosed in eight patients, benign villous
      adenoma was seen in one patient, and celiac disease in another, although duodenal
      biopsies were taken in only 15 patients. Erosions and/or ulcerations were found
      in four of 11 patients (36%) using NSAIDs and/or salicylates (ASA). Seventy
      percent of the lesions were found in elderly patients (>65 years), 56% of whom
      were using NSAIDs and/or ASA. Conclusions: EGD should always be performed in
      patients with iron deficiency anemia after a negative colonoscopy, although upper
      gastrointestinal malignancy will probably be an infrequent finding. The presence
      of a significant, treatable lesion is most likely in the elderly and in those
      with a history of NSAID or ASA use. Routine duodenal biopsies should be performed
      to further increase the outcome of EGD.

PMID- 11297916
TI  - Visceral leishmaniasis in a patient with acquired hypogammaglobulinemia.
AB  - A case of visceral leishmaniasis in a 26-year-old man with acquired IgA and IgG2
      hypogammaglobulinemia, secondary to carbamazepine therapy given because of a
      previous head injury, is presented. The patient's clinical picture was otherwise
      typical, although hypogammaglobulinemia resulted in a delay in diagnosis, and
      response to therapy was excellent. This case is noteworthy because it is the
      first reported case of visceral leishmaniasis in a hypogammaglobulinemic patient
      and also because it is the fifth case of hypogammaglobulinemia due to
      carbamazepine reported worldwide.

PMID- 11297917
TI  - Cardiac malignant lymphoma successfully treated with chemotherapy.
AB  - We report the case of an 83-year-old woman with diffuse large B-cell lymphoma
      located in the right cardiac ventricle revealed by acute congestive heart
      failure. Complete and long-lasting disappearance of the cardiac tumor was
      observed with monochemotherapy (cyclophosphamide).

PMID- 11297918
TI  - CD4(+) T-lymphocytopenia and Pneumocystis carinii pneumonia in a patient with
      miliary tuberculosis.
AB  - We report a case of miliary tuberculosis (MTB) occurring after extracorporeal
      shock-wave lithotripsy in a 51-year-old man. The MTB was complicated by
      pancytopenia and CD4(+) T-lymphocytopenia, which was responsible for Pneumocystis
      carinii pneumonia. Hematological parameters returned to normal in response to
      antituberculous treatment.

PMID- 11297920
TI  - Macromolecular assemblages. Theory and simulation.
AB  - A selection of World Wide Web sites relevant to papers published in this issue of
      Current Opinion in Structural Biology.

PMID- 11297922
TI  - Atomic structures at last: the ribosome in 2000.
AB  - Last year, atomic structures of the 50S ribosomal subunit from Haloarcula
      marismortui and of the 30S ribosomal subunit from Thermus thermophilus were
      published. A year before that, a 7.8 A resolution electron density map of the 70S
      ribosome from T. thermophilus appeared. This information is revolutionizing our
      understanding of protein synthesis.

PMID- 11297923
TI  - Bacterial RNA polymerase.
AB  - The recently determined crystal structure of a bacterial core RNA polymerase
      (RNAP) provides the first glimpse of this family of evolutionarily conserved
      cellular RNAPs. Using the structure as a framework, a consistent picture of
      protein-nucleic acid interactions in transcription complexes has been accumulated
      from cross-linking experiments. The molecule can be viewed as a molecular
      machine, with distinct structural features hypothesized to perform specific
      functions. Comparison with the alpha-carbon backbone of a eukaryotic RNAP reveals
      close structural similarity.

PMID- 11297924
TI  - Structural insights into the molecular mechanism of calcium-dependent vesicle
      membrane fusion.
AB  - The fusion of vesicles with target membranes is controlled by a complex network
      of protein-protein and protein-lipid interactions. Recently determined structures
      of the SNARE complex, synaptotagmin III, nSec1, domains of the NSF chaperone and
      its adaptor (SNAP), and Rab3 and some of its effectors provide the framework for
      developing molecular models of vesicle fusion and for designing experiments to
      test these models. Ultimately, knowledge of the structures of higher-order
      complexes and their dynamic behavior will be required to obtain a full
      understanding of the vesicle fusion protein machinery.

PMID- 11297925
TI  - Gamma-tubulin complexes and microtubule nucleation.
AB  - Microtubules are dynamic cytoskeletal polymers that assemble from alpha/beta
      tubulin and are vital for the establishment of cell polarity, vesicle trafficking
      and formation of the mitotic/meiotic spindle. gamma-Tubulin, a protein related to
      alpha/beta-tubulin, is required for initiating the polymerization of microtubules
      in vivo. gamma-Tubulin has been found in two main protein complexes: the gamma
      tubulin ring complex and its subunit, the gamma-tubulin small complex. The latter
      is analogous to the yeast Tub4 complex. In the past year, important advances have
      been made in understanding the structure and function of the gamma-tubulin ring
      complex and how it interacts with microtubules.

PMID- 11297926
TI  - Myosin motors: missing structures and hidden springs.
AB  - High-resolution structures of the motor domain of myosin II and lower resolution
      actin-myosin structures have led to the "swinging lever arm" model for myosin
      force generation. The available kinetic data are not all easily reconciled with
      this model and understanding the final details of the myosin motor mechanism must
      await actin-myosin co-crystals. The observation that myosin can populate multiple
      states in the absence of actin has nonetheless led to significant insights. The
      currently known myosin structures correspond to defined kinetic states that bind
      weakly (K(d)>microM) to actin. It is possible that the myosin lever arm could
      complete its swing before strong binding to actin and force generation--a process
      that would correspond, in the absence of load, to a Brownian ratchet. We further
      suggest that, under load, internal springs within the myosin head could decouple
      force generation and lever arm movement.

PMID- 11297927
TI  - The familiar and the unexpected in structures of icosahedral viruses.
AB  - Viruses were the first large macromolecular assemblages to be visualized at high
      resolution. New virus structures continue to challenge our understanding of
      specificity in protein-protein "recognition". The evolution of virus structures
      has been even more opportunistic than previously imagined.

PMID- 11297928
TI  - Recent advances in FRET: distance determination in protein-DNA complexes.
AB  - Fluorescence resonance energy transfer (FRET) provides information on the
      distance between a donor and an acceptor dye in the range 10 to 100 A. Knowledge
      of the exact positions of some dyes with respect to nucleic acids now enables us
      to translate these data into precise structural information using molecular
      modeling. Advances in the preparation of dye-labeled nucleic acid molecules and
      in new techniques, such as the measurement of FRET in polyacrylamide gels or in
      vivo, will lead to an increasingly important role of FRET in structural and
      molecular biology.

PMID- 11297930
TI  - What can we learn about protein folding from Ising-like models?
AB  - Ising-like models have been remarkably successful in reproducing all the
      experimental data available on the equilibrium and kinetics of secondary
      structure formation in short peptides. Over the past two years, very similar
      models have been used to predict the folding of complete proteins, with
      encouraging results. Although Ising-like models are probably too simple to
      describe all aspects of protein folding, the results obtained so far indicate
      that they can play a critical role in the study of protein folding by bridging
      the gap between experiment and more detailed theoretical approaches.

PMID- 11297931
TI  - New developments in applying quantum mechanics to proteins.
AB  - Algorithmic improvements of quantum mechanical methodologies have increased our
      ability to study the electronic structure of fragments of a biomolecule (e.g. an
      enzyme active site) or entire biomolecules. Three main strategies have emerged as
      ways in which quantum mechanics can be applied to biomolecules. The supermolecule
      approach continues to be utilized, but it is slowly being replaced by the so
      called coupled quantum mechanical/molecular mechanical methodologies. An exciting
      new direction is the continued development and application of linear-scaling
      quantum mechanical approaches to biomolecular systems.

PMID- 11297932
TI  - Steered molecular dynamics and mechanical functions of proteins.
AB  - Atomic force microscopy of single molecules, steered molecular dynamics and the
      theory of stochastic processes have established a new field that investigates
      mechanical functions of proteins, such as ligand-receptor binding/unbinding and
      elasticity of muscle proteins during stretching. The combination of these methods
      yields information on the energy landscape that controls mechanical function and
      on the force-bearing components of proteins, as well as on the underlying
      physical mechanisms.

PMID- 11297933
TI  - Statistical potentials and scoring functions applied to protein-ligand binding.
AB  - In virtual screening, small-molecule ligands are docked into protein binding
      sites and their binding affinity is predicted. Knowledge-based, regression-based
      and first-principle-based methods have been developed to rank computer-generated
      binding modes. As a result of still existing deficiencies, a best compromise
      might be the combination of several scoring schemes into a consensus scoring
      approach.

PMID- 11297934
TI  - Polarizable force fields.
AB  - Standard force fields used in biomolecular computing describe electrostatic
      interactions in terms of fixed, usually atom-centered, charges. Real physical
      systems, however, polarize substantially when placed in a high-dielectric medium
      such as water--or even when a strongly charged system approaches a neutral body
      in the gas phase. Such polarization strongly affects the geometry and energetics
      of molecular recognition. First introduced more than 20 years ago, polarizable
      force fields seek to account for appropriate variations in charge distribution
      with dielectric environment. Over the past five years, an accelerated pace of
      development of such force fields has taken place on systems ranging from liquid
      water to metalloenzymes. Noteworthy progress has been made in better
      understanding the capabilities and limitations of polarizable models for water
      and in the formulation and utilization of complete specifically parameterized
      polarizable force fields for peptides and proteins.

PMID- 11297935
TI  - Macromolecular electrostatics: continuum models and their growing pains.
AB  - Theoretical understanding of macromolecular electrostatics has advanced
      substantially over the past year. Continuum models have given promising results
      for calculating protein-ligand binding free energy differences, as well as pK(a)s
      and redox properties, particularly with explicit treatment of multiple
      conformers. Generalized Born and other techniques have led to the first molecular
      dynamics simulations of proteins and RNA with continuum solvent. Continuum and
      microscopic descriptions of dielectric relaxation have been critically compared.

PMID- 11297936
TI  - Electrostatics calculations: recent methodological advances and applications to
      membranes.
AB  - Calculations of electrostatic energies and forces are at the heart of the
      theoretical modeling of biological molecules. During the past year, new methods
      for accurately treating electrostatic interactions have been developed for all
      atom simulations and for modeling systems in which the uninteresting part of the
      system, for example, the solvent, is represented implicitly. Recent applications
      of electrostatic energy calculations have revealed new principles concerning the
      role of electrostatics in peptide binding to membranes and ion transport across
      membranes through protein channels.

PMID- 11297938
TI  - Cryptic splicing involving the splice site mutation in the canine model of
      Duchenne muscular dystrophy.
AB  - Golden retriever muscular dystrophy arises from a mutation in the acceptor splice
      site of intron 6 of the dystrophin gene. Skipping of exon 7 disrupts the mRNA
      reading frame and results in premature termination of translation. We are using
      this animal model to evaluate treatments for Duchenne muscular dystrophy,
      including gene repair induced by chimeric oligonucleotides. After injection of
      golden retriever muscular dystrophy (GRMD) muscle with a chimeric oligonucleotide
      to repair the lesion, immunostaining revealed a modest increase in the number of
      dystrophin-positive fibres at the injection sites. Dystrophin gene transcripts
      containing exon 7 were detected by reverse transcription-polymerase chain
      reaction, suggesting that low levels of splice site correction may have occurred.
      However, DNA sequencing of these apparently normal dystrophin gene transcripts
      revealed that the first five bases of exon 7 were missing. It will be important
      to be aware of this phenomenon with respect to further gene correction studies in
      the canine model.

PMID- 11297939
TI  - The lacZ gene under the control of the 7 kb of human dystrophin muscle specific
      promoter is expressed in cardiac muscle but not in adult skeletal muscle in
      transgenic mice.
AB  - In previous transgenic studies, we reported a 0.9 kb fragment from a mouse
      dystrophin muscle promoter that contains the regulatory elements required for
      expression of dystrophin only in the right heart. In this study, to further
      characterize the regulation of muscle type of promoter, we analyzed promoter
      activity and tissue specificity using a total 14 kb fragment around the human
      dystrophin muscular-specific exon 1 in vitro and in vivo. In vitro analysis
      showed that the lacZ construct of the 7 kb promoter and 7 kb intron 1 was
      expressed 2.5 times as strong as the lacZ construct of only the 7 kb promoter in
      C2/4 myotubes. In vivo analysis revealed expression of both constructs in the
      whole heart, skeletal muscle and vascular smooth muscle in embryos. However, in
      adults, the expression in skeletal muscle disappeared. We conclude that the 7 kb
      upstream region and the 7 kb intronic region included responsible elements for
      the expression in the heart, but not in skeletal muscle in vivo. It is possible
      that a strong enhancer element for skeletal muscle exists in some other region.

PMID- 11297940
TI  - Activation of calcineurin and stress activated protein kinase/p38-mitogen
      activated protein kinase in hearts of utrophin-dystrophin knockout mice.
AB  - Dilated cardiomyopathy is a common complication of Duchenne and Becker muscular
      dystrophies, which are caused by mutations in the dystrophin gene. The mdx mouse
      is an animal model for Duchenne muscular dystrophy (DMD) and shows mildly
      dystrophic changes in the heart. By contrast, the utrophin-dystrophin knockout
      (dko) mouse shows severe dystrophic changes in cardiac muscle, that more closely
      resembles DMD cardiomyopathy than mdx mouse. However the pathogenesis of
      development has not been fully understood. Recently many reports have revealed
      that calcineurin and stress activated protein kinase (SAPK)/p38-mitogen activated
      protein kinase (MAPK) hypertrophic signalling pathways are associated with the
      development of some forms of hypertrophic and dilated cardiomyopathies. These
      signalling pathways may have some roles in the development of dystrophin
      deficient cardiomyopathy. Here we report that calcineurin and SAPK/p38-MAPK
      signalling pathways were constantly activated in dko hearts, but the activation
      varied in mdx hearts. The pathogenesis of the development of dystrophin-deficient
      cardiomyopathy may be associated with the activation of these signalling
      pathways.

PMID- 11297941
TI  - IGF-I treatment improves the functional properties of fast- and slow-twitch
      skeletal muscles from dystrophic mice.
AB  - Although insulin-like growth factor-I (IGF-I) has been proposed for use by
      patients suffering from muscle wasting conditions, few studies have investigated
      the functional properties of dystrophic skeletal muscle following IGF-I
      treatment. 129P1 ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer from a
      deficiency in the structural protein, laminin, and exhibit severe muscle wasting
      and weakness. We tested the hypothesis that 4 weeks of IGF-I treatment (
      approximately 2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutaneously)
      would increase the mass and force producing capacity of skeletal muscles from
      dystrophic mice. IGF-I treatment increased the mass of the extensor digitorum
      longus (EDL) and soleus muscles of dystrophic mice by 20 and 29%, respectively,
      compared with untreated dystrophic mice (administered saline-vehicle only).
      Absolute maximum force (P(o)) of the EDL and soleus muscle was increased by 40
      and 32%, respectively, following IGF-I treatment. Specific P(o) (sP(o)) was
      increased by 23% in the EDL muscles of treated compared with untreated mice, but
      in the soleus muscle sP(o) was unchanged. IGF-I treatment increased the
      proportion of type IIB and type IIA fibres and decreased the proportion of type I
      fibres in the EDL muscles of dystrophic mice. In the soleus muscles of dystrophic
      mice, IGF-I treatment increased the proportion of type IIA fibres and decreased
      the proportion of type I fibres. Average fibre cross-sectional area was increased
      in the EDL and soleus muscles of treated compared with untreated mice. We
      conclude that IGF-I treatment ameliorates muscle wasting and improves the
      functional properties of skeletal muscles of dystrophic mice. The findings have
      important implications for the role of IGF-I in ameliorating muscle wasting
      associated with the muscular dystrophies.

PMID- 11297942
TI  - Identification of altered gene expression in skeletal muscles from Duchenne
      muscular dystrophy patients.
AB  - Mutations in the dystrophin gene lead to dystrophin deficiency, which is the
      cause of Duchenne muscular dystrophy (DMD). This important discovery more than 10
      years ago opened a new field for very productive investigations. However, the
      exact functions of dystrophin are still not fully understood and the complex
      process leading to subsequent muscle fiber necrosis has not been clearly
      described; hence there has not yet been any marked improvement in patient
      treatment. To decipher the molecular mechanisms induced by a lack of dystrophin,
      we started identifying genes whose expression is altered in DMD skeletal muscles.
      The approach was based on differential screening of a human muscle cDNA array.
      Nine genes were found to be up- or downregulated. Our results indicate expression
      alterations in mitochondrial genes, titin, a muscle transcription factor and
      three novel genes. First characterizations of these novel genes indicated that
      two of them have striated muscle tissue specificity.

PMID- 11297943
TI  - Vitamin E and exertional rhabdomyolysis during endurance sled dog racing.
AB  - Exertional rhabdomyolysis (ER) is common in sled dogs, animals with high energy
      expenditures that consume high fat (60% of ingested calories) diets. Associations
      between pre-race plasma [vitamin E] and total antioxidant status (TAS) and risk
      of developing ER were examined in dogs competing in the 1998 Iditarod race. Pre
      race blood samples were collected from 750 dogs and a second sample was collected
      from 158 dogs withdrawn from the race at various times. Plasma creatine kinase
      activity was used to identify withdrawn dogs with ER. There was no association
      between pre-race plasma [vitamin E] and risk of development of ER. Dogs that
      developed ER started the race with higher TAS, but when withdrawn, had lower TAS
      than unaffected dogs and had similar pre-race [vitamin E] but higher [vitamin E]
      at time of withdrawal. Hence, the risk of ER in sled dogs is not affected by
      plasma [vitamin E] before the race.

PMID- 11297944
TI  - The phenotype of calpainopathy: diagnosis based on a multidisciplinary approach.
AB  - Calpainopathy (LGMD2A) is the most common type of autosomal recessive limb-girdle
      muscular dystrophy. We performed a systematic clinical evaluation in 13
      calpainopathy patients from 11 families, with particular attention to the pattern
      of muscle involvement. Eleven patients had a muscle biopsy with deficiency of
      calpain 3 on western blotting. The other two patients were not biopsied as they
      were siblings from the same families. Confirmatory CAPN3 mutations were detected
      in seven patients. The age at presentation was 2-45 years, wider than previously
      reported. We confirm the highly characteristic and recognisable phenotype of
      predominant muscular atrophy with early pelvic girdle involvement, relative
      sparing of the hip abductors, scapular winging and abdominal laxity. Early
      primary contractures were also a prominent feature in this group, expanding the
      breadth of the phenotype. Recognition of the clinical pattern of calpainopathy is
      of diagnostic significance. It is important, especially in sporadic cases, in
      targeting and interpreting laboratory investigations in order to provide accurate
      diagnostic and prognostic information.

PMID- 11297945
TI  - Early white matter changes on brain magnetic resonance imaging in a newborn
      affected by merosin-deficient congenital muscular dystrophy.
AB  - In 1996 we reported sequential magnetic resonance imaging study in an infant with
      merosin-deficient congenital muscular dystrophy with normal brain magnetic
      resonance imaging at 3 weeks and white matter changes by 6 months. We now report
      an infant with merosin-deficient congenital muscular dystrophy with a mild degree
      of white matter changes already present on brain magnetic resonance imaging at 5
      days of age. The difference may be due to a difference in the T2 sequences used.
      The images in this present case were obtained with a fast spin echo sequence
      (echo time: 210 ms). The increased T2 weighted may be responsible for a better
      detection of the white matter changes at an early stage, when they can be missed
      on conventional, less weighting T2 sequences. These results suggest that, by
      using appropriate sequences, mild white matter changes may be detectable on brain
      magnetic resonance imaging in the first days of life in infants with merosin
      deficient congenital muscular dystrophy.

PMID- 11297946
TI  - A case of MERRF associated with chronic pancreatitis.
AB  - We report the first case to our knowledge of chronic pancreatitis associated with
      mitochondrial encephalopathy with the A8344G mitochondrial DNA (mtDNA) mutation.
      This 10-year-old-girl had suffered from recurrent abdominal pain with elevated
      serum amylase and lipase since the age of 6, and easy fatigability, tremor and
      astatic seizures since the age of 8. A biopsy of quadriceps muscle revealed
      ragged-red-fibers and cytochrome c oxidase deficiency. Analysis of mtDNA in
      peripheral blood identified an A8344G mutation in the mitochondrial tRNA(Lys)
      gene. Taken together with physical signs of myoclonic seizures and cerebellar
      dysfunction, we diagnosed her as myoclonic epilepsy with ragged-red fibers
      associated with chronic pancreatitis. Although no association between
      mitochondrial disease and pancreatitis has yet been established, this case
      suggests it is necessary to consider the participation of mitochondrial
      abnormality in the pathogenesis of recurrent pancreatitis.

PMID- 11297947
TI  - Monomelic amyotrophy with late progression.
AB  - Monomelic amyotrophy is a sporadic juvenile-onset disease that presents with
      gradual onset of weakness and atrophy in the hand muscles unilaterally.
      Generally, this disease is considered a 'benign' and non-progressive motor neuron
      disease, which stabilizes within five years of onset. We discuss a case that
      illustrates that monomelic amyotrophy may rarely exhibit late clinical
      progression to the lower extremities after a prolonged period of disease
      stability.

PMID- 11297948
TI  - 79(th) ENMC International Workshop: multifocal motor neuropathy. 14-15 April
      2000, Hilversum, The Netherlands.

PMID- 11297949
TI  - 73(rd) ENMC International Workshop: congenital myasthenic syndromes. 22-23
      October, 1999, Naarden, The Netherlands.

PMID- 11297950
TI  - Reducing the stigma of mental illness.

PMID- 11297951
TI  - Value of sonography in diagnosis of rheumatoid arthritis.

PMID- 11297952
TI  - Toll of allergy reduced by probiotics.

PMID- 11297953
TI  - Implications of pathogenetic and prognostic features for management of
      myelodysplastic syndromes.

PMID- 11297954
TI  - Treatment of severe autonomic orthostatic hypotension.

PMID- 11297955
TI  - Levels and kinds of evidence for public-health nutrition.

PMID- 11297956
TI  - Effect of lipid-lowering therapy on early mortality after acute coronary
      syndromes: an observational study.
AB  - BACKGROUND: Lipid-lowering agents are known to reduce long-term mortality in
      patients with stable coronary disease or significant risk factors. However, the
      effect of lipid-lowering therapy on short-term mortality immediately after an
      acute coronary syndrome has not been determined. We did an observational study
      using data from two randomised trials to investigate this issue. METHODS: We used
      data from the GUSTO IIb and PURSUIT trials to compare all-cause mortality among
      patients with acute coronary syndromes who were discharged on lipid-lowering
      agents (n=3653) with those who were not (n=17,156). A propensity analysis was
      done to adjust for presumed selection biases in the prescription of lipid
      lowering agents. FINDINGS: Lipid-lowering therapy was associated with a smaller
      proportion of deaths at 30 days (17 [0.5%] vs 179 [1.0%], hazard ratio 0.44 [95%
      CI 0.27-0.73], p=0.001) and at 6 months (63 [1.7%] vs 605 [3.5%], 0.48 [0.37
      0.63], p<0.0001). After adjustment for the propensity to be prescribed lipid
      lowering agents and other potential confounders, prescription of a lipid-lowering
      agent at discharge remained associated with a reduced risk of death at 6 months
      (0.67 [0.48-0.95], p=0.023). INTERPRETATION: Prescription of a lipid-lowering
      drug at hospital discharge was independently associated with reduced short-term
      mortality among patients after an acute coronary syndrome.

PMID- 11297957
TI  - Biochemical markers of liver fibrosis in patients with hepatitis C virus
      infection: a prospective study.
AB  - BACKGROUND: Liver biopsy is thought mandatory for management of patients with
      hepatitis C virus (HCV) infection, especially for staging fibrosis. We aimed, in
      our prospective study, to assess the predictive value of a combination of basic
      serum biochemical markers for diagnosis of clinically significant fibrosis
      (including early stages). METHODS: We assessed liver-biopsy patients with
      detectable HCV by PCR, for eligibility, and took a blood sample on the day of the
      procedure. The analysis was done in a first-year period for 205 patients and then
      tested in a second period on 134 patients. We devised a fibrosis index that
      included the most informative markers (combined with age and sex) for the first
      year group. 11 serum markers were assessed as well as fibrosis stage: F0=no
      fibrosis and F1=portal fibrosis; and for clinically significant fibrosis, F2=few
      septa, F3=many septa, and F4=cirrhosis. Statistical analysis was by logistic
      regression, neural connection, and receiver-operating characteristic (ROC)
      curves. FINDINGS: First-year and second-year patient-group characteristics and
      biochemical markers did not differ. The overall frequency of clinically
      significant fibrosis was 40% (138 patients). The most informative markers were:
      alpha2 macroglobulin, alpha2 globulin (or haptoglobin), gamma globulin,
      apolipoprotein A1, gamma glutamyltranspeptidase, and total bilirubin. The areas
      (SD) under the ROC curves for the first-year (0.836 [0.430]) and second-year
      groups (0.870 [0.340]) did not differ (p=0.44). With the best index, a high
      negative predictive value (100% certainty of absence of F2, F3, or F4) was
      obtained for scores ranging from zero to 0.10 (12% [41] of all patients), and
      high positive predictive value (>90% certainty of presence of F2, F3, or F4) for
      scores ranging from 0.60 to 1.00 (34% [115] of all patients). INTERPRETATION: A
      combination of basic serum markers could be used to substantially reduce the
      number of liver biopsies done in patients with chronic HCV infection.

PMID- 11297958
TI  - Probiotics in primary prevention of atopic disease: a randomised placebo
      controlled trial.
AB  - BACKGROUND: Reversal of the progressive increase in frequency of atopic disease
      would be an important breakthrough for health care and wellbeing in western
      societies. In the hygiene hypothesis this increase is attributed to reduced
      microbial exposure in early life. Probiotics are cultures of potentially
      beneficial bacteria of the healthy gut microflora. We assessed the effect on
      atopic disease of Lactobacillus GG (which is safe at an early age and effective
      in treatment of allergic inflammation and food allergy). METHODS: In a double
      blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to
      mothers who had at least one first-degree relative (or partner) with atopic
      eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their
      infants. Chronic recurring atopic eczema, which is the main sign of atopic
      disease in the first years of life, was the primary endpoint. FINDINGS: Atopic
      eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was
      diagnosed in six of these children and allergic rhinitis in one. The frequency of
      atopic eczema in the probiotic group was half that of the placebo group (15/64
      [23%] vs 31/68 [46%]; relative risk 0.51 [95% CI 0.32-0.84]). The number needed
      to treat was 4.5 (95% CI 2.6-15.6). INTERPRETATIONS: Lactobacillus GG was
      effective in prevention of early atopic disease in children at high risk. Thus,
      gut microflora might be a hitherto unexplored source of natural immunomodulators
      and probiotics, for prevention of atopic disease.

PMID- 11297959
TI  - Zinc supplementation during pregnancy and effects on growth and morbidity in low
      birthweight infants: a randomised placebo controlled trial.
AB  - BACKGROUND: Infant malnutrition and mortality rates are high in less-developed
      countries especially in low-birthweight infants. Zinc deficiency is also widely
      prevalent in these circumstances. We aimed to assess the effect of daily zinc
      supplements given to pregnant mothers on their infants' growth and morbidity.
      METHODS: We did a double-blind, placebo controlled, randomised trial in 199 and
      221 Bangladeshi infants whose mothers took 30 mg daily elemental zinc or placebo,
      respectively, from 12 to 16 weeks' gestation until delivery. Infants were
      followed up until 6 months of age. We obtained data for morbidity every week by
      mothers' recall. Infants' anthropometric measurements were done every month, and
      their serum zinc was assessed at 1 and 6 months of age. FINDINGS: Infants of
      mothers who received zinc during pregnancy had at age 6 months reduced risks
      compared with those in the placebo group for acute diarrhoea (risk ratio 0.84;
      95% CI 0.72-0.98), dysentery (0.36; 0.25-0.84), and impetigo (0.53; 0.34-0.82).
      These reductions were seen in low-birthweight infants but not in those with
      normal birthweight. There were no differences in infant growth or serum zinc
      concentrations between treatment groups. INTERPRETATION: Maternal zinc
      supplementation during pregnancy resulted in a reduction of the health risks in
      Bangladeshi low-birthweight infants, although this intervention did not improve
      birthweight. Whether zinc should be added to usual antenatal supplements in
      regions with high rates of low birthweight should be reviewed.

PMID- 11297960
TI  - Rapid magnetic resonance angiography for detection of atherosclerosis.
AB  - BACKGROUND: Choice of treatment for atherosclerosis depends on various clinical
      factors and radiological techniques. We aimed to assess the diagnostic accuracy
      of a new three-dimensional magnetic resonance angiography (3D MRA) strategy for
      the display of arterial vasculature from supra-aortic arteries to distal runoff
      vessels in 72 s. METHODS: We examined five healthy volunteers and six patients
      over 6 weeks. Conventional digital subtraction angiography (DSA) was available as
      reference standard in all six patients. Magnetic resonance imaging was done on a
      commercially available 1.5 Tesla scanner. The imaging technique was based on the
      acquisition of five 3D data sets in rapid succession with an optimum single
      injection protocol. FINDINGS: Compared with conventional catheter angiography,
      according to the findings of two independent and masked readers, whole-body MRA
      had overall sensitivities of 91% (95% CI 0.76-0.98) and 94% (0.8-0.99), and
      specificities of 93% (0.85-0.97) and 90% (0.82-0.96) for the detection of
      substantial vascular disease (luminal narrowing >50%), interobserver agreement
      for assessment of whole-body magnetic angiograms was very good (kappa=0.94; 95%
      CI 0.9-0.98). INTERPRETATION: The technique provides a comprehensive non-invasive
      approach for morphological screening assessment of the arterial vasculature from
      supra-aortic arteries to the distal runoff arteries.

PMID- 11297961
TI  - Recurrent reversible paraplegia.

PMID- 11297962
TI  - Prospective survey of childhood inflammatory bowel disease in the British Isles.
AB  - The incidence of inflammatory bowel disease in children in western countries may
      be rising. Since there is no prospective national data on the incidence of
      inflammatory bowel disease in the UK and Republic of Ireland (ROI), we undertook
      a prospective survey to determine this incidence. The incidence during 1998 and
      1999 was 5.2/100,000 per year in children aged younger than 16 years. Those from
      an Asian background were over-represented and more likely to have ulcerative
      colitis.

PMID- 11297963
TI  - UK collaborative randomised trial of neonatal extracorporeal membrane
      oxygenation: follow-up to age 4 years.
AB  - Extracorporeal membrane oxygenation (ECMO) is a supportive intensive-care
      technique used for babies with acute respiratory failure. We examined morbidity
      at age 4 years in surviving children recruited to the UK Collaborative ECMO
      Trial, and provide long-term data on ECMO support compared with contemporary
      conventional care. The neonatal ECMO policy resulted in improved survival and a
      favourable outcome. We therefore advocate the safety and efficacy of this
      intervention.

PMID- 11297964
TI  - Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of
      severely injured patients.
AB  - A single base pair insertion/deletion (4G/SG) promoter polymorphism in the
      plasminogen-activator-inhibitor-1 (PAI-1) gene is thought to play a part in
      prognosis after severe trauma. We investigated the relation between outcome of
      severe trauma, PAI-1 concentrations, and PAP-1 genotype in 61 patients who had
      been severely injured. 11 (58%) of 19 patients with genotype 4G/4G did not
      survive, whereas only eight (28%) of 29 patients with heterozygous genotype
      4G/SG, and two (15%) of 13 patients with genotype 5G/5G died. The PAI-1 4G allele
      is associated with high concentrations of PAI-1 in plasma and a poor survival
      rate after severe trauma.

PMID- 11297965
TI  - Women's shoes and knee osteoarthritis.
AB  - We assessed whether wearing wide-heeled shoes has a similar effect on knee torque
      to narrow-heeled shoes by measuring the joint torques of 20 healthy women during
      walking. Wearing wide-heeled shoes had a 30% greater effect on peak external knee
      flexor torque than walking barefoot. Walking with wide-heeled and narrow-heeled
      shoes increased peak knee varus torque by 26% and 22%, respectively. Our findings
      imply that wide-heeled shoes cause abnormal forces across the patellofemoral and
      medial compartments of the knee, which are the typical anatomical sites for
      degenerative joint changes.

PMID- 11297966
TI  - Stem cells get to the heart of the matter.

PMID- 11297967
TI  - Why is rickets resurgent in the USA?

PMID- 11297968
TI  - Contraceptive implant matches effect of IUDs and sterilisation.

PMID- 11297969
TI  - European congress hears urgent call to fight hospital-acquired infections.

PMID- 11297971
TI  - Time to concentrate on DNA control.

PMID- 11297972
TI  - Too many monitors check UK health care's vital signs.

PMID- 11297974
TI  - Canadian university publishes new rules to protect scientists.

PMID- 11297975
TI  - US court rules in favour of radical anti-abortion activists.

PMID- 11297976
TI  - Kenya debates tobacco bill that aims to reduce smoking-related disease.

PMID- 11297977
TI  - Health, trade, and industry officials set to debate access to essential drugs.

PMID- 11297978
TI  - India's scientists question need for research on smallpox virus.

PMID- 11297981
TI  - The implantable cardioverter defibrillator.
AB  - Implantable cardioverter defibrillators (ICDs) have evolved from the treatment of
      last resort to the gold standard therapy for patients at high risk for
      ventricular tachyarrhythmias. High-risk patients include those who have survived
      life-threatening arrhythmias, and individuals with cardiac diseases who are at
      risk for such arrhythmias, but are symptomless. Use of an ICD will affect the
      patient's quality of life. Some drugs can substantially affect defibrillator
      function and efficacy, and possible drug-device interactions should be
      considered. Patients with ICDs may encounter cell phones, antitheft detectors,
      and many other sources of potential electromagnetic Interference. In addition to
      treating ventricular tachyarrhythmias, new defibrillators provide full featured
      dual chamber pacing, and could treat atrial arrhythmias, and congestive heart
      failure by means of biventricular pacing.

PMID- 11297982
TI  - Osteoarthritis as a systemic disorder including stromal cell differentiation and
      lipid metabolism.
AB  - For many years articular cartilage has been the focus of research aimed at
      improving understanding of and treatment for osteoarthritis. Although much is
      known about the tissue, research has had little success in elucidating the
      pathogenesis of generalised osteoarthritis. A new hypothesis is required.
      Substantial changes in many tissues, including bone, muscle, ligaments, and joint
      capsule, as well as cartilage, are increasingly recognised in this disease, and
      not all these changes are localised to the affected joints. There is also a well
      established link with obesity. These observations, the common origins of the
      mesenchymal cells that maintain these tissues, and the possible role of
      neuroendocrine factors that can regulate bone mass, result in the hypothesis that
      systemic factors that include altered lipid metabolism could explain the
      diversity of physiological changes in generalised osteoarthritis. If proven, this
      hypothesis could have important implications for a new approach to
      pharmacological intervention in the early stages of the disease.

PMID- 11297983
TI  - Democracy and health care in Serbia.

PMID- 11297984
TI  - Aid and safety for Guinea's refugees.

PMID- 11297985
TI  - Which comes first--health or wealth?

PMID- 11297989
TI  - Etiquette and relationships.

PMID- 11297986
TI  - Drug-resistant tuberculosis: desperate measures?

PMID- 11297996
TI  - Prophylactic antidepressants.

PMID- 11297997
TI  - Introducing chemists to food allergy.
AB  - Adverse reactions to food may be toxic or non toxic, depending on the
      susceptibility to a certain food; non toxic reactions that involve immune
      mechanisms are termed allergy if they are IgE-mediated. If no immunological
      mechanism is responsible, it is termed intolerance. The following disorders are
      considered a consequence of food allergy: gastrointestinal reactions (oral
      allergy syndrome, vomiting, diarrhea, protein-induced enterocolitic syndrome,
      eosinophilic gastroenteritis); respiratory reactions (rhinitis, asthma, laryngeal
      edema); cutaneous reactions (urticaria-angioedema, atopic dermatitis);
      anaphylaxis. There is much recent evidence to consider celiac disease an
      immunological disorder. Food allergy diagnosis is based on history, SPT, specific
      IgE, food challenges. DBPCFC is fundamental for diagnosing true food allergy;
      patients who have had anaphylaxis to food must not undergo DBPCFC. Rapidly
      progressive respiratory reactions and anaphylactic shock are life-threatening
      reactions that can be caused by food allergy. The doses of food inducing
      anaphylaxis can be very low, therefore commercial cross-contamination with an
      unsuspected food during food processing can be risky for the food allergic
      patient. The prevention of severe anaphylactic food reactions may lie in
      interdisciplinary collaboration among allergologists, chemists, food
      technologists, and experts in food industry research.

PMID- 11297998
TI  - Introducing allergists to food chemistry.
AB  - A report of common analytical methods for the identification and characterization
      of food allergens is presented. The different electrophoretic and immunologic
      methods describe the present analytical tools to characterize allergens. With
      respect to the lack of knowledge on the structure and the properties of food
      allergens, additional chemical techniques such as chromatography, NMR and MALDI
      TOF are of particular importance.

PMID- 11297999
TI  - Oral tolerance to protein antigens.
AB  - Oral tolerance is an active non-response to antigens delivered via the oral
      route. Mechanisms governing tolerance induction have been well characterized in
      mouse. Similar studies in man are lacking, although there is evidence that
      tolerance can be induced. In disease states, tolerance is altered and this may
      account for the presence of mucosal inflammation. In food hypersensitivity there
      is evidence that allergens may be handled differently and this may play a role in
      disease expression.

PMID- 11298000
TI  - Nature and function of gastrointestinal antigen-presenting cells.
AB  - Antigen-presenting cells (APCs) of the human gut are heterogeneous, including
      both macrophages, a variety of dendritic cells and B cells. They are found both
      in gut-associated lymphoid tissue and in the mucosal lamina propria, especially
      beneath the surface epithelium. APCs have diverse phenotypes and therefore
      probably different functions in various locations; their expression levels of a
      variety of costimulatory molecules are most likely important for immunological
      decision making of stimulated T cells, either locally in the gut or in regional
      lymph nodes to which migrating APCs (dendritic cells) carry antigen. Thus, APCs
      are involved in active immunity as well as in induction of oral tolerance.
      However, their precise role in food allergy remains to be defined.

PMID- 11298001
TI  - Gastrointestinal eosinophils.

PMID- 11298002
TI  - Breast milk--immunomodulatory signals against allergic diseases.
AB  - Breastfeeding holds a key position with regard to the increasing burden of
      allergic diseases in the industrialized countries. Not only does it provide the
      infant with nutrients for growth and development, it also confers immunological
      protection during a critical period in life, when the infant's own defense
      mechanisms are immature. A delicate balance of stimulatory, even inflammatory,
      maturational signals, together with a myriad of anti-inflammatory compounds, is
      transferred from mother to infant via breastfeeding. Breastfeeding mothers,
      however, do not constitute a uniform group. The composition of breast milk shows
      marked individual variation and so, consequently, does the success of
      breastfeeding in reducing the risk of disease. Recent clinical studies indicate
      that the potential of breastfeeding to counteract allergic disease may be
      promoted by dietary means. While uncoordinated elimination diets result in a risk
      of general nutritional inadequacy or deficiency of essential single nutrients, a
      balanced diet following current dietary recommendations, specifically containing
      fresh fruits and vegetables (antioxidants) and fat of predominantly vegetable
      origin, may be associated with a lower incidence of atopy in the infant. As early
      nutrition appears to program the subsequent health of the child, the importance
      of the maternal dietary composition during breastfeeding should be emphasized. In
      future, an improved understanding of the mechanisms of this programming may offer
      specific therapeutic modalities for the prevention of allergic disease.

PMID- 11298003
TI  - Structural aspects of cross-reactivity and its relation to antibody affinity.
AB  - In the context of IgE/allergen interactions, affinity is largely determined by
      the stability of the allergen-IgE complex: a low affinity is usually equated with
      a rapid dissociation of the complex. Regular solid-phase assays are not well
      suited for affinity estimates because of multivalency effects, "unstirred layer"
      effects and "invisible" antibodies. Elution of IgE bound to solid-phase coupled
      allergen might be a good measure of intrinsic affinity, provided that
      reassociation of antibodies is prevented by a high concentration of soluble
      allergen. Allergen-mediated IgE-dependent triggering of a mast cell is presumably
      a two-step process. During the first step, the allergen is bound to a cell-bound
      IgE antibody and dragged over the cell surface. The second step is the
      interaction between this cell-bound allergen and another IgE antibody. The
      hypothesis is that the affinity requirements for the first step are higher than
      for the second. The implication is that a mast cell can be triggered by a single
      high-affinity antibody in combination with one or more low-affinity antibodies.

PMID- 11298004
TI  - High throughput screening: a rapid way to recombinant allergens.
AB  - Complex allergenic sources such as moulds, foods and mites contain large panels
      of IgE-binding molecules which need to be cloned, produced and characterized in
      order to mimic the entire allergenicity of whole extracts reconstituted by mixing
      single standardized recombinant allergens. Phage display of cDNA libraries allows
      selective enrichment of allergen-expressing clones using IgE from allergic
      patients. For the characterization of all different clones present in enriched
      cDNA libraries in a fast and cost-effective way, however, high-throughput
      screening technology is required. We have used a high-throughput, quantitative
      technology for fast identification of all different clones present in selectively
      enriched phage surface-displayed cDNA libraries in order to characterize whole
      allergenic repertoires from complex allergenic sources. The strategy, based on a
      combination of phage display and high-density arrays, allowed fast discovery of
      panels of related structures from different allergenic sources. They cover
      secreted, cytoplasmic and structural proteins with or without enzymatic activity
      and offer a rational explanation for the IgE-mediated cross-reactivity frequently
      encountered in clinical practice.

PMID- 11298005
TI  - Structure and function of milk allergens.
AB  - Proteins (CMP) involved in milk allergy are numerous and heterogeneous, with very
      few structural or functional common features. This heterogeneity is complicated
      by their genetic polymorphism, resulting in several variants for each protein.
      These variants are characterized by point substitutions of amino acids or by
      deletions of peptide fragments of varying size or by post-translational
      modifications such as phosphorylation or glycosylation. All of these
      modifications may affect allergenicity. No common molecular structure can be
      associated with allergenicity, although some homologous regions such as casein
      phospho-peptides can explain an IgE cross-reactivity. Three-dimensional structure
      is an important feature in CMP allergenicity but denatured and linear epitopes
      are also involved. Epitopes are numerous and widely spread along the CMP
      molecule. They may be located in hydrophobic parts of the molecule where they are
      inaccessible for IgE antibodies in the native conformation of the protein but
      become bioavailable after digestive processes. Peptides as short as ca. 12-14
      amino acid residues may account for a significant part of the allergenicity of
      the whole molecule, which justifies the need to be careful before proposing any
      CMP hydrolysate for highly allergenic children.

PMID- 11298006
TI  - Allergens from fish and egg.
AB  - Allergens from fish and egg belong to some of the most frequent causes of food
      allergic reactions reported in the literature. Egg allergens have been described
      in both white and yolk, and the egg white proteins ovomucoid, ovalbumin,
      ovotransferrin and lysozyme have been adopted in the allergen nomenclature as Gal
      d1-d4. The most reported allergen from egg yolk seems to be alpha-livitin. In
      fish, the dominating allergen is the homologues of Gad c1 from cod, formerly
      described as protein M. A close cross-reactivity exists within different species
      of fish between this calcium-binding protein family, denominated the
      parvalbumins. This cross-reactivity has been indicated to be of clinical
      relevance for several species, since patients with a positive double-blind,
      placebo-controlled food challenge to cod will also react with other fish species,
      such as herring, plaice and mackerel. In spite of the importance of these two
      allergen systems, only a few studies have been performed, and the scarcity of
      cloned allergens from both of the systems is emphasized.

PMID- 11298007
TI  - Plant food allergens homologous to pathogenesis-related proteins.
AB  - In general, pathogenesis-related (PR) proteins are expressed by plants in
      response to stress conditions like infection, exposure to certain chemicals,
      wounding and environmental conditions. In some plant tissues, however, PR
      proteins are constitutively expressed, e.g. in pollens or fruits, tissues that
      are more likely to be attacked (by insects or fungi) or exposed to atmospheric
      conditions (e.g. UV irradiation). PR proteins display multiple effects within the
      plant and possess antimicrobial activity, and can thus be regarded as a part of
      the plant's defense system. Analyzing known amino acid sequences and functions of
      characterized (cloned) food allergens, it is remarkable that many of these
      molecules can be classified as PR proteins. Many PR proteins are stable at low
      pH, and display considerable resistance to proteases, requirements to act as food
      allergens. According to sequence characteristics and their enzymatic or biologic
      activity, PR proteins can be divided into 14 groups. Seven of these 14 groups
      contain proteins with allergenic properties, six groups contain food allergens.

PMID- 11298008
TI  - Lipid transfer proteins and 2S albumins as allergens.
AB  - Plant lipid transfer proteins, a widespread family of proteins, have been
      recently identified as important food allergens. Their common structural
      features, such as eight conserved cysteines forming disulfide bridges, basic
      isoelectric point and high similarity in amino acid sequence, are the basis of
      allergic clinical cross-reactivity. This has been demonstrated for the LTP
      allergens of the Prunoideae subfamily, whose similarity is about 95% as
      demonstrated for the purified allergens of peach, apricot, plum and apple. A
      relevant aspect is the existence of sequence homology of LTPs of botanically
      unrelated foods, as demonstrated for LTPs of maize and peach. A class of food
      allergens of well recognized clinical importance is that of seed storage 2S
      albumins. They have been identified in the most diffused edible seeds and nuts,
      such as mustard, sesame, Brazil nut, walnut and peanut. In particular, a strong
      correlation between IgE-binding to these proteins and food-induced anaphylaxis
      has been demonstrated for Brazil nut and sesame seeds.

PMID- 11298009
TI  - Lipocalin allergens.
AB  - Most animal-derived major allergens causing respiratory sensitization belong to
      the family of proteins called lipocalins. Their sequential identity varies but
      the three-dimensional structure is conserved. They are present in body fluids and
      secretions. Several lipocalins are able to bind and transport small hydrophobic
      ligands like retinol. The immunological characteristics of lipocalin allergens
      are poorly known. Cow dust-derived allergen, Bos d2, which is a potent inducer of
      IgE production, was observed to induce the weak proliferative responses of
      peripheral blood mononuclear cells of asthmatic patients upon stimulation in
      vitro. The responses were Th2-deviated and directed to a few epitopes in Bos d2.
      One of the epitopes, situated adjacent to a structurally conserved region of
      lipocalins, was recognized by the T cells of all patients. Computer predictions
      suggested that human endogenous lipocalins may contain epitopes in the
      corresponding region. We have proposed that the allergenicity of lipocalins may
      be associated with the adaptation of the immune system to the presence of
      endogenous lipocalins.

PMID- 11298010
TI  - Impact of (bio)chemical and physical procedures on food allergen stability.
AB  - A variety of methods have been used to attempt to decrease the allergenicity of
      food products, with highly variable success. Limited knowledge of allergen and
      epitope structures and the factors governing their stability may explain this,
      and the ensuing need for an empirical approach. A combined effort from a
      processing and genomics-based approach may open up new ways to improve the
      quality of foods from an allergenic perspective. Based on structural knowledge, a
      suitable approach can be chosen that is, for instance, heat stable but protease
      sensitive; protease resistant but not heat stable; easy to extract; easy to mask
      because the epitope is exactly on a crosslink site; a molecular probe design that
      allows screening of germplasm collections.

PMID- 11298011
TI  - How can thermal processing modify the antigenicity of proteins?
AB  - This paper is a brief review of thermally induced covalent modifications to
      proteins in foods, focussing mainly on the advanced glycation end-products (AGE)
      of the Maillard reaction. Most foods are subjected to thermal processing, either
      in the home or during their production/manufacture. Thermal processing provides
      many beneficial effects, but also brings about major changes in allergenicity.
      Far from being a general way to decrease allergenic risk, thermal processing is
      as likely to increase allergenicity as to reduce it, through the introduction of
      neoantigens. These changes are highly complex and not easily predictable, but
      there are a number of major chemical pathways that lead to distinct patterns of
      modification. Perhaps the most important of these is through the reaction of
      protein amino groups with sugars, leading to an impressive cocktail of AGE
      modified protein derivatives. These are antigenic and many of the important
      neoantigens found in cooked or stored foods are probably such Maillard reaction
      products. A deeper understanding of thermally induced chemical changes is
      essential for more advanced risk assessments, more effective QC protocols,
      production of more relevant diagnostic allergen extracts and the development of
      novel protein engineering and therapeutic approaches to minimise allergenic risk.

PMID- 11298012
TI  - How to make foods safer--genetically modified foods.
AB  - It is the responsibility of companies developing genetically modified foods, and
      of regulatory authorities that approve their marketing, to ensure that they are
      at least as safe as the traditional foods they are intended to replace in the
      diet. This requires that any novel material introduced into the food material
      should not be allergenic. If the novel gene has come from an allergenic source,
      e.g. nuts, it is necessary to demonstrate using immunological procedures applied
      to the IgE fractions of pooled sera from individuals with confirmed allergies
      that the novel protein is non-allergenic. When the novel gene is from a non
      allergenic source then it is necessary to demonstrate lack of significant amino
      acid sequence homology to known allergens together with sensitivity to food
      manufacturing and digestive processes. Consumer confidence in genetically
      modified foods would be significantly improved if hypoallergenic varieties of
      crops and food products that are currently allergenic could be developed.
      Techniques such as antisense technology and single site amino acid substitution
      have been shown to have such potential.

PMID- 11298013
TI  - Ingredient and labeling issues associated with allergenic foods.
AB  - Foods contain a wide range of food ingredients that serve numerous technical
      functions. Per capita consumer exposure to most of these food ingredients is
      rather low with a few notable exceptions such as sugar and starch. Some food
      ingredients including edible oils, hydrolyzed proteins, lecithin, starch,
      lactose, flavors and gelatin may, at least in some products, be derived from
      sources commonly involved in IgE-mediated food allergies. These ingredients
      should be avoided by consumers with allergies to the source material if the
      ingredient contains detectable protein residues. Other food ingredients,
      including starch, malt, alcohol and vinegar, may be derived in some cases from
      wheat, rye or barley, the grains that are implicated in the causation of celiac
      disease. If these ingredients contain gluten residues, then they should be
      avoided by celiac sufferers. A few food ingredients are capable of eliciting
      allergic sensitization, although these ingredients would be classified as rarely
      allergenic. These ingredients include carmine, cochineal extract, annatto,
      tragacanth gum and papain. Food manufacturers should declare the presence of
      allergenic food ingredients in the ingredient listings on product labels so that
      allergic consumers can know to avoid these potentially hazardous products.

PMID- 11298014
TI  - Standardization of in vitro methods.
AB  - IgE-antibody analysis is a major diagnostic procedure and a primary tool in
      allergological research. The determination of sensitization frequencies and
      antibody concentrations against allergens of defined sources provides critical
      information for the estimation of the relative importance of food and environment
      in clinical allergy. True quantitation is essential and requires assay designs
      providing allergen excess and mass unit calibration. Standardized and
      reproducible methods show geographic and culture dependent differences between
      patient populations and contribute to the quality of diagnosis and treatment of
      allergic disease.

PMID- 11298015
TI  - Standardization of double-blind, placebo-controlled food challenges.
AB  - At present, no international agreement on standardized protocols for use in
      double-blind placebo-controlled food challenge exists. There is a great need for
      such standardization, both for clinical and for scientific reasons.

PMID- 11298016
TI  - Optimized allergen extracts and recombinant allergens in diagnostic applications.

PMID- 11298017
TI  - Statistical model for assessing the proportion of subjects with subjective
      sensitisations in adverse reactions to foods.
AB  - The outcome from a Double-Blind Placebo-Controlled Food Challenge is often of a
      subjective nature and cannot be measured directly. Reactions to placebo
      challenges are frequently observed, implying that some of the responses in the
      study are in fact 'false responses'. In order to adjust for these false
      responses, previous studies have used various methods, including removing
      subjects from the analysis who reacted to the placebo. Simply ignoring the false
      responses can lead to misleading estimates for the true proportion of sensitised
      individuals. This paper outlines two models which can account for these false
      responses. In the single challenge study, a simple model is developed which
      enables the estimation of the rate of false responses in the study, as well as
      the true proportion of sensitised subjects. This model is very easy to apply in
      practice. For a repeated challenge study, a more complicated model is developed
      which again enables the estimation of the rate of false responses and the true
      proportion of sensitised subjects.

PMID- 11298018
TI  - The threshold concept in food safety and its applicability to food allergy.
AB  - Down the years there have been many clinical reports of exquisite sensitivity to
      low doses of food allergens. There are many factors that may contribute to a
      variation of threshold in an individual exposed to an allergen during the course
      of his or her daily life. Some of these factors are intrinsic and unavoidable.
      Other factors may be predictable but not easily controllable, such as asthma,
      exposure to allergens during the pollen season and predicting situations that may
      be risky. Other factors may be out of the control of the individual. The most
      important one of these is the adequate training and awareness of manufacturers
      and caterers who aim to provide safe and nutritious meals to their allergic and
      non-allergic customers alike. Clinical histories of reactions in the community
      and the use of labial exposure during food challenge show that most non-ingestion
      exposures to peanut usually result in easily treated minor reactions. Formal,
      oral food challenges have shown that low dose reactivity is relatively common but
      studies have not yet had the power to investigate whether peanut allergy is more
      commonly associated with very low dose reactivity than other foods. This means
      that industry must not concentrate only on peanut and tree nuts when looking at
      issues of contamination just because they are associated with the majority of
      severe reactions. There are more milk and egg allergic children in the general
      population and they deserve the same protection from allergen exposure as
      sufferers of peanut or tree nut allergies.

PMID- 11298019
TI  - Where are we in risk assessment of food allergens? The regulatory view.
AB  - Assessing the risk of exposure to chemicals is done every day worldwide. This
      assessment includes hazard identification, dose (concentration)-response (effect)
      assessment, exposure assessment and risk characterization. The present paper
      discusses the possibilities and limitations of using these procedures when
      assessing the risk of food allergens. It is concluded that hazard identification
      is not a problem. The medical literature is full of descriptions of cases of food
      allergy where the offending food or even allergen is identified. More knowledge
      on the relationship between dose and response of different allergens in different
      patient populations is needed. Exposure assessment is possible but may not be
      easy. Determining the distribution of contamination with an allergen may be
      crucial. To do risk characterization, and as a consequence to be able to manage
      risk, knowledge of a threshold for effect is needed and the possibility of using
      a safety factor. If we do not manage to establish thresholds for elicitation of
      allergic response in food allergy, risk assessment and management will be very
      difficult. It will be difficult to avoid labeling like "May contain peanuts" used
      with and without reason. In the long run, unjustified warnings will not help the
      allergic consumer but will create more confusion than guidance.

PMID- 11298020
TI  - Risk assessment for food allergy--the industry viewpoint.
AB  - A safe food supply is a legitimate expectation of consumers, which the food
      industry must meet. Allergic reactions to food are recognised as a significant
      public health problem. Protecting allergic consumers against such reactions,
      while minimising the impact of food allergy on their quality of life, poses a
      challenge to the industry. Risk assessment is the process whereby the likelihood
      of an adverse event is related to exposure. Allergic reactions to foods can arise
      in one of three ways, which are not mutually exclusive. Firstly, a known allergen
      may be present in a food at a level above that at which the allergic individual
      reacts, secondly, an individual may react to a known or novel allergen because of
      sensitisation to another, cross-reactive, allergen and finally sensitisation may
      occur to a novel allergen, followed by reaction on subsequent exposure. A total
      absence of risk of reaction to an allergen implies no exposure, a situation which
      in most food manufacturing environments is unrealistic, and in any event would
      not help in the context of novel allergens. Possible approaches to risk
      assessment for food allergy in each of the contexts described above are examined,
      together with their limitations.

PMID- 11298021
TI  - Skin manifestations in food allergy.
AB  - Skin manifestations represent the most often observed clinical symptoms in food
      allergy. Immediate symptoms are urticaria, angioedema and sudden erythema
      (flush). Delayed symptoms which can be observed are exanthema and exacerbation or
      worsening of eczema (most often atopic dermatitis). Since delayed symptoms are
      difficult to diagnose, oral provocation tests are often necessary for patients
      with a suspected late onset of symptoms upon food ingestion. There is evidence
      that besides specific IgE, specific T cells play a role in the deterioration of
      eczema in atopic dermatitis. Although urticarial skin lesions are most often
      observed upon oral provocation with a suspected food, the rate of IgE-mediated
      food allergy in acute or chronic urticaria is rather low. In some patients
      suffering from chronic urticaria, intolerance reactions are also suspected. Since
      no laboratory or skin tests are available yet for the identification of
      clinically relevant food additives causing urticaria, oral provocation tests are
      mandatory for these patients.

PMID- 11298022
TI  - Food-induced anaphylaxis.
AB  - To date, there are no population-based epidemiologic studies providing
      information about the prevalence of food-induced anaphylaxis. However, statistics
      from the United Kingdom demonstrated an increase of anaphylaxis from 5.6 cases
      per 100,000 hospital discharges in 1991-92 to 10.2 cases in 1994-95. The increase
      for the subcategory of food-induced anaphylaxis was above the overall increase in
      anaphylaxis. In the UK register of fatal anaphylactic reactions, all food-induced
      fatalities have been accompanied by respiratory problems with respiratory arrest.
      Atopic individuals with bronchial asthma and prior allergic reactions to the same
      food are at a particularly high risk. Not only peanuts, seafood and milk can
      induce severe, potentially lethal, anaphylaxis, but indeed a wide spectrum of
      foods, according to the different patterns of food sensitivity in different
      countries. Foods with "hidden" allergens and meals at restaurants are
      particularly dangerous for patients with food allergies. Similarly, schools,
      public places and restaurants are the major places of risk. However, the main
      factor contributing to a fatal outcome is the fact that the victims did not carry
      their emergency kit with adrenaline (epinephrine) with them. Therefore, we
      suggest that the pharmaceutical industry should reintroduce an adrenaline inhaler
      that is more effective, especially in asthmatic reactions.

PMID- 11298023
TI  - Milk allergy/intolerance and atopic dermatitis in infancy and childhood.
AB  - Adverse reactions to cow's milk proteins are usually indicated as cow's milk
      allergy/intolerance (CMPA/CMPI) because no differentiation is possible on the
      basis of symptoms, and there is no reliable single laboratory test available for
      the diagnosis of CMPA or CMPI. Elimination and challenge tests for cow's milk
      proteins using strict, well-defined diagnostic criteria are required for the
      diagnosis of CMPA/CMPI. Atopic dermatitis (AD) is one of the most common symptoms
      of CMPA/CMPI. Approximately one third of AD children have a diagnosis of
      CMPA/CMPI according to elimination diet and challenge tests, and about 40-50% of
      children < 1 year of age with CMPA/CMPI have AD. Many children with AD and
      CMPA/CMPI develop a complete tolerance to CMP in a few years. Children with
      persisting forms of CMPA/CMPI have a more frequent history of familial atopic
      disease, change in CMPA/CMPI manifestations over time and very high frequency of
      multiple food intolerance and allergic diseases. Many children who outgrow their
      AD develop other allergic diseases, such as rhinitis or asthma. The simultaneous
      development of allergic tolerance in one organ and the intolerance or atopic
      disease in another organ suggest that genetic, immunologic and environmental
      factors play a complex role in the natural history of AD and other atopic
      diseases.

PMID- 11298024
TI  - Nickel allergy, a model of food cellular hypersensitivity?

PMID- 11298025
TI  - Food allergen avoidance in primary prevention of food allergy.
AB  - Approximately 5-10% of children suffer from allergy to one or more foods. Primary
      prevention through a hypoallergenic diet may reduce the prevalence of food
      allergy and associated co-morbidity, such as eczema and urticaria. Breastfeeding
      has many advantages and should be recommended for all children. Those with a
      history of atopy in the immediate family are at a higher risk and maternal diet
      during lactation, avoiding highly allergenic foods, may enhance the benefit.
      Cow's milk should be strictly avoided, and supplements, if required, should be
      with a hypoallergenic formula. Delayed introduction of egg, nuts, wheat and fish
      has also been suggested. Dietary restriction may have nutritional consequences
      for the mother and child and supervision by a dietician is essential. Maternal
      diet during pregnancy is not advisable as the benefit is minimal and there may be
      adverse effects on the foetal nutrition. In high risk infants, a combined
      approach, where breastfeeding with maternal avoidance of highly allergenic foods,
      supplemented by extensively hydrolysed formula during the first 6 months of life,
      in addition to the delayed introduction of solid foods, has been shown to reduce
      the development of food allergy in infants.

PMID- 11298026
TI  - Food allergen avoidance--the patient's viewpoint.
AB  - The profile of potentially fatal food allergies has altered in recent years. The
      vigilance required for allergen avoidance when shopping or eating out depends on
      information which is often hidden or misleading. Families with allergic children
      suffer social exclusion and stress, made worse by a serious shortage of
      specialist patient care. Those who die are usually teenagers and young adults who
      suffer from severe allergic asthma or anaphylaxis after eating away from the
      home. A recognised manufacturing standard would endorse businesses seeking to
      remove the risk of allergen cross-contamination, whilst the integration of
      allergy into training for caterers and environmental health professionals would
      influence and inform foodservice businesses.

PMID- 11298027
TI  - Classic specific immunotherapy and new perspectives in specific immunotherapy for
      food allergy.
AB  - Food allergy is a major cause of life-threatening hypersensitivity reactions.
      Food-induced anaphylaxis is the most common reason for someone to present to the
      emergency department for an anaphylactic reaction. The avoidance of the
      allergenic food is the only method of preventing further reactions that is
      currently available for sensitized patients. Strict avoidance of specific foods
      is the accepted treatment of food-induced allergic reactions but is often an
      unrealistic therapeutic option for food-induced hypersensitivity reactions for
      the many reasons previously described. Desirable therapeutic strategies for the
      treatment and prevention of food allergies must be safe, relatively inexpensive
      and easily administered. Recent advances in the understanding of the
      immunological mechanisms underlying allergic disease and better characterization
      of food allergens have greatly expanded the potential therapeutic options for
      future use. Several different forms of immunomodulatory therapies are currently
      under investigation: peptide immunotherapy, mutated protein immunotherapy,
      allergen DNA immunization, vaccination with immunostimulatory DNA sequences and
      anti-immunoglobulin E (Anti-IgE) therapy.

PMID- 11298028
TI  - Probiotics and prebiotics and food intolerance.

PMID- 11298029
TI  - DNA-based vaccination for the treatment of food allergy.
AB  - At present, avoidance is the only therapeutic option available for individuals
      with food allergies. However, studies suggest that DNA-based vaccination might be
      an effective therapeutic option for the reversal of allergic hypersensitivities,
      including allergies to foods. Because severe anaphylactic reactions represent a
      life-threatening risk for individuals with food allergies, we and others have
      evaluated the effectiveness of DNA-based vaccination for the prevention of
      anaphylactic hypersensitivity in murine models. Our investigations demonstrated
      that primary gene and protein/immunostimulatory sequence oligodeoxynucleotide
      (ISS-ODN) vaccination of subsequently Th2-sensitized mice reduced the risk of
      death after anaphylactic challenge, significantly. In addition, gene and
      protein/ISS-ODN vaccination reduced post challenge plasma histamine levels.
      Analysis of the immune profiles of mice receiving DNA-based vaccines showed that
      both gene and protein/ISS-ODN vaccination effectively prevented the development
      of Th2-biased immune profiles after sensitization. In contrast, vaccination with
      protein alone, the experimental equivalent of the traditional protein-based
      immunotherapy (IT) reagents used in clinical practice provided no protection from
      anaphylaxis, nor did it prevent the development of a Th2-biased immune profile
      after allergen sensitization. These studies justify continued optimism in the
      potential of DNA-based vaccination for the desensitization of food allergic
      individuals.

PMID- 11298030
TI  - State-of-the-art staging in prostate cancer.

PMID- 11298031
TI  - Radical radiation therapy options for organ-confined prostate cancer.

PMID- 11298032
TI  - Erectile dysfunction in relation to traumatic pelvic injuries or pelvic
      fractures.

PMID- 11298033
TI  - The management of female urinary stress incontinence: II. The use of devices.

PMID- 11298034
TI  - The relationship between early renal status, and the resolution of vesico
      ureteric reflux and bladder function at 16 months.
AB  - OBJECTIVE: To examine, in infants presenting with vesico-ureteric reflux (VUR),
      the relationship between the presence of initial renal abnormalities with the
      outcome of VUR and bladder function at 16 months of age. PATIENTS AND METHODS:
      The study group comprised 40 infants (32 boys) presenting consecutively (29 after
      prenatal detection) with VUR grade III or greater (bilateral in 29) on the
      initial micturating cystogram (median age 8 weeks). The initial presence of
      abnormal kidneys was determined from isotopic renography and/or ultrasonography.
      These data were correlated with the outcome of VUR, from direct isotope
      cystography, and bladder function assessed by natural filling urodynamics,
      examined at age 16 months (mean 16.4 months, SD 2.1). RESULTS: Three groups were
      identified. Group 1 (eight boys and six girls) had normal kidneys bilaterally;
      initially grade III VUR was common. At 16 months bladder function was normal in
      10 children and none had VUR (complete resolution). Group 2 (14 boys and two
      girls) had unilateral renal abnormalities; initially VUR was predominantly grade
      IV or grade V. At 16 months bladder function was normal in eight children and VUR
      resolved in eight, five of these with normal bladder function. Group 3 (10 boys)
      had bilateral renal abnormalities. Initially grade V VUR predominated; at 16
      months the bladder function was normal in only one, and in the rest the emptying
      dynamics were abnormal. All 10 boys had persisting VUR (no resolution).
      CONCLUSIONS: In infants with moderate or severe VUR, resolution at 16 months old
      is associated with normal kidneys in a similar proportion of boys and girls.
      Resolution also correlates well with normal bladder function. Presentation in
      infancy with bilateral abnormal kidneys, associated with severe VUR in boys, is a
      poor prognostic sign for the early outcome of VUR and for bladder function.

PMID- 11298035
TI  - Scintigraphic screening for renal damage in siblings of children with symptomatic
      primary vesico-ureteric reflux.
AB  - OBJECTIVE: To define prospectively the incidence of renal parenchymal lesions in
      the siblings of patients treated at one institution for primary vesico-ureteric
      reflux (VUR). PATIENTS AND METHODS: From January 1997 to October 1998, a
      prospective study including renal scintigraphy (using dimercaptosuccinic acid,
      DMSA) and a radionuclide cystogram was proposed systematically to the
      asymptomatic siblings of children treated for primary VUR. The radionuclide
      cystograms were interpreted as showing the presence or absence of VUR and the
      DMSA scan as symmetrical or asymmetrical differential function, with or with no
      renal defect. RESULTS: Fifty-five families gave informed consent, of whom 46
      completed the study (eight refused secondarily and one was omitted by exclusion
      criteria), representing 46 symptomatic patients and 65 siblings. There were 17
      siblings with VUR (26%) including two of 13 infants and 15 of 52 children aged >
      18 months. One radionuclide cystogram failed. Of the 17 refluxing siblings, four
      had a history of symptomatic urinary tract infection; 62 of the 65 siblings had a
      DMSA scan, of which 56 were normal and six (10%) showed abnormalities (five
      asymmetrical differential function and one parenchymal defect). Only one of these
      six patients had VUR at the time of the evaluation and only one had a small
      kidney detected by ultrasonography on one side (and no VUR). There were no
      adverse effects associated with screening. CONCLUSION: This study confirms a
      significant overall incidence of VUR (26%) in the asymptomatic siblings of
      patients treated for primary VUR. From the results of the DMSA scan (only one
      sibling had a parenchymal defect), the systematic screening of asymptomatic
      siblings does not appear to be beneficial.

PMID- 11298036
TI  - A noninvasive test for vesico-ureteric reflux in children.
AB  - OBJECTIVE: To report the development and testing of a device for the noninvasive
      diagnosis of vesico-ureteric reflux (VUR) which avoids the need for urethral
      catheterization (currently required to reliably determine the presence of VUR),
      and which thus avoids the anxiety of parents and patients that causes many
      families to refuse such evaluation. PATIENTS AND METHODS: Fifty-four children (49
      girls and five boys, mean age 7.2 years, range 4-14) previously evaluated as
      having VUR volunteered to participate; no child was symptomatic at the time of
      the study. Refluxing units were known to be present by voiding cysto
      urethrography (within 1 year, mean 7 months) in 45 and absent in 16. The device
      developed acquires electronically processed acoustic signals from the child
      during an observed urination. The signals are then analysed 'off-line' to
      determine the presence or absence of VUR. The initial preparation for the test
      included: (i) a full bladder [at least 0.80 x ((2 + age) x 30 mL)] measured by
      ultrasonography; and (ii) localization of the pelvi-ureteric junction by
      ultrasonography to accurately place the device's sensors on the child's back. The
      children were then positioned at a commode after placing the sensors; the
      recording was started and continued until voiding occurred. The children were
      tested with the recording and analysis team unaware of the presence and/or degree
      of VUR. The first 47 studies were single-kidney examinations and the remaining
      seven included simultaneous monitoring of both kidneys. RESULTS: Sixty-one renal
      units were assessed and interpretable signals were obtained from 54 (89%). There
      were seven episodes of 'system failure' when no interpretable data were obtained.
      One unit with no VUR had a 'reflux' signal; in four kidneys, spontaneous (two)
      and postsurgical (two) resolution of reflux was predicted by the testing and
      subsequently verified by cyclic radionuclide cystography. CONCLUSIONS: This
      noninvasive diagnostic technique detected VUR in 35 of 37 refluxing units and
      verified no reflux in 16 of 17 units without VUR. Further refinements may allow
      this technology to be used in all children with suspected VUR.

PMID- 11298037
TI  - Bladder functional outcome after delayed vesicostomy closure and antireflux
      surgery in young infants with 'primary' vesico-ureteric reflux.
AB  - OBJECTIVE: To evaluate bladder function by conventional urodynamic investigations
      in young infants with primary vesico-ureteric reflux (VUR) who had undergone an
      initial temporary cutaneous vesicostomy followed by later antireflux surgery and
      vesicostomy closure. PATIENTS AND METHODS: From 1983 to 1990, nine boys (10-360
      days old) with primary VUR were treated with an initial vesicostomy, followed by
      delayed closure of the vesicostomy and the simultaneous surgical correction of
      reflux. Severe VUR was detected bilaterally in seven and unilaterally in two
      infants at the time of the initial diagnosis. The mean (SD, range) age at
      vesicostomy was 12.4 (8, 3-23) months and the duration of bladder
      defunctionalization 38.7 (25.5, 18-90) months. All patients were assessed
      urodynamically after closing the vesicostomy, using rapid-fill cystometry with
      normal saline solution at room temperature. The mean (range) age at the time of
      urodynamic testing was 7.3 (5-15) years; the mean (SD, range) follow-up was 10.1
      (4.1, 5-17) years. RESULTS: Six boys with bilateral VUR underwent successful
      ureteroneocystostomy; nephroureterectomy was required in one patient. In two
      patients the VUR resolved with time. After re-functionalization, the mean (SD,
      range) maximum cystometric capacity, expressed as a percentage of the mean
      bladder capacity for age, was 1.4 (0.5, 0.6-2.2)%. In three patients the bladder
      capacity was higher (> or = 40%) than expected for age, while one had diminished
      (< 70%) bladder capacity. The mean (range) end-filling detrusor pressure was 14.5
      (5-42) cmH2O and the mean (SD, range) compliance 24 (13.9, 4-44) mL/cmH2O. Two
      patients had a compliance of < 10 mL/cmH2O, one of whom had associated unstable
      detrusor contractions of 90 cmH2O. The mean (SD, range) detrusor voiding pressure
      at peak flow was 47.3 (16.8, 5-76) cmH2O. One patient had a residual urine volume
      of 8% of bladder capacity. At the follow-up, only one patient (aged 5 years) with
      detrusor instability had urinary incontinence. CONCLUSION: This study shows that
      the bladder of young infants with primary VUR treated with temporary vesicostomy
      regained normal function after re-functionalization of the lower urinary tract.

PMID- 11298038
TI  - Is the vanished testis always a scrotal event?
AB  - OBJECTIVE: To determine if perinatal testicular torsion resulting in a vanished
      testis is an event that primarily occurs in the scrotum. PATIENTS AND METHODS:
      The records of 54 boys identified as having a solitary testis were reviewed. The
      side of absence, size of the solitary testis, method of surgical evaluation
      (scrotal, inguinal or abdominal), surgical findings and histology of the tissue
      removed were noted. RESULTS: The testis was absent twice as often on the left
      side, the solitary testis was hypertrophic in 25 of 42 boys in whom it was
      evaluated, and tissue grossly or histologically consistent with a testicular
      'nubbin' was removed in 52 boys. Scrotal (47) or inguinal (seven) exploration was
      carried out in all. Laparoscopy (28) or abdominal exploration (two) was
      undertaken to confirm that no testicular tissue was present in the abdomen in 30
      boys, including the two in whom no tissue was found on scrotal or inguinal
      exploration. CONCLUSIONS: Perinatal testicular torsion occurs after descent but
      before fixation of the tunica vaginalis to the scrotal wall. These testes
      atrophy, leaving a remnant of tissue in the scrotum that can be identified on
      scrotal exploration in almost all cases. Therefore, it is recommended that the
      evaluation of the child with a solitary palpable testis start with scrotal
      exploration. Laparoscopy should be reserved for those in whom no tissue
      consistent with a testicular nubbin is found in the scrotum.

PMID- 11298039
TI  - A multi-institutional analysis of laparoscopic orchidopexy.
AB  - OBJECTIVE: To combine and analyse the results from centres with a large
      experience of laparoscopy for the impalpable testis with small series, to
      determine the expected success rate for laparoscopic orchidopexy. METHODS: A
      questionnaire was distributed to participating paediatric urologists; each
      contributor retrospectively reviewed the clinical charts for their cases of
      therapeutic laparoscopy for an impalpable testis, detailing 36 variables for each
      patient. The data were collated centrally into a computerized database. For
      inclusion, the testis was intra-abdominal (including 'peeping' at the internal
      ring) at laparoscopic examination, was not managed through an open approach and
      did not undergo orchidectomy. Three surgical groups were assessed, with success
      defined as lack of atrophy and intrascrotal position: group 1, primary
      laparoscopic orchidopexy; group 2, a one-stage Fowler-Stephens (F-S) orchidopexy;
      and group 3, a two-stage F-S orchidopexy. RESULTS: Data were gathered from 10
      centres in the USA, covering the period 1990-1999; 252 patients representing 310
      testes were included and overall, 15.2% were lost to follow-up. There was no
      significant difference between success rates in the larger and smaller series.
      Atrophy occurred in 2.2% of 178 testes, 22.2% of 27 testes and 10.3% of 58 testes
      in groups 1-3, respectively. Testes were not in a satisfactory scrotal position
      in 0.6%, 7.4% and 1.7% of groups 1-3, respectively. The mean follow-up for each
      group was 7.7, 8.6 and 20.0 months, respectively. The overall success for all
      groups was 92.8% (97.2% group 1; 74.1% group 2; 87.9% group 3), with an atrophy
      rate of 6.1%. CONCLUSION: Laparoscopic orchidopexy for the intra-abdominal
      testis, in both large and small series, can be expected to have a success rate
      higher than that historically ascribed to open orchidopexy. Within this series,
      single-stage F-S laparoscopic orchidopexy resulted in a significantly higher
      atrophy rate than the two-stage repair. However, when considering both F-S
      approaches, the laparoscopic approach gave greater success than previously
      reported for the same open approaches. Despite the weaknesses inherent in a
      retrospective unrandomized study, we conclude that laparoscopic orchidopexy is,
      if not the procedure of choice, an acceptable and successful approach to the
      impalpable undescended testicle.

PMID- 11298040
TI  - Laparoscopic orchidopexy: a review of a large clinical series.
AB  - OBJECTIVE: To report the overall success rate of a laparoscopic orchidopexy (LO)
      series over 5 years including over 100 procedures. PATIENTS AND METHODS: The
      records were reviewed of children who underwent laparoscopic procedures for an
      impalpable testis at our institutions. The laparoscopic procedures included the
      standard LO and one-stage and staged Fowler-Stephens (F-S) LOs. The success of
      orchidopexy was defined as a testis in the scrotum with no atrophy after surgery.
      RESULTS: From 1994, 80 children (101 impalpable testes) were treated using LO. Of
      these patients, 20 (25%) had impalpable testes on the right, 39 (50%) were on the
      left and 21 (25%) were bilateral. The testicular location was identified during
      laparoscopy as: intra-abdominal in 46, iliac in 14, in the internal ring in 22,
      'peeping' in 12, behind the bladder in three and intracanulicular in four.
      Standard LO was used in 72 testes, a one-stage F-S in 20 and a two-stage F-S in
      nine (first stage two, second stage seven). The median (range) age of the
      patients was 18 months (0.5-12 years); the mean (range) follow-up was 5 (1-36)
      months. After orchidopexy the testis was scrotal in 90 (low 78, mid four and high
      eight), at the pubis in one and not stated in seven (no follow-up available).
      Four patients (4%) had testicular atrophy from failed F-S orchidopexies, two of
      whom had undergone previous testicular surgery and one caused by additional
      dissection around the vas. The overall success rate, including only those with
      follow-up, was 96% (90 of 94). Of the 20 one-stage F-S orchidopexies, 17 testes
      were successfully placed in the scrotum with no atrophy. The overall success rate
      for all F-S procedures was 85% (23 of 27). However, excluding patients who had
      previous testicular surgery or who required extensive dissection near the vas,
      96% (23 of 24) of the testes were successfully placed into the scrotum with no
      atrophy. CONCLUSION: The high overall success rate in placing the testis into the
      scrotum through laparoscopic procedures is considerably better than reported in
      other series to date. LO is an effective method for managing intra-abdominal
      testes in children. Patients who had undergone previous surgery had a higher risk
      of developing testicular atrophy. The additional dissection around the vas almost
      inevitably leads to testicular atrophy.

PMID- 11298042
TI  - Varicocele in adolescence induces left and right testicular volume loss.
AB  - OBJECTIVE: To determine the effect of a palpable left-sided varicocele (which in
      adolescent patients can adversely affect left testicular volume) on right
      testicular volume with progressive Tanner development and increasing varicocele
      grade. PATIENTS AND METHODS: The right and left testicular volumes were measured
      with a standard orchidometer in 70 control patients (mean age 14.6 years, SD 2.2)
      with no palpable testicular abnormality and in 434 (mean age 14.3 years, SD 2.3)
      with a palpable left-sided varicocele. Patients with bilateral and right-sided
      varicoceles were excluded from the study. RESULTS: There was no significant
      difference between the left and right testicular volumes in the control patients.
      The testicular volumes of patients with a grade I varicocele were similar to
      those in control patients. Patients with a grade II varicocele had a
      significantly smaller left testis than the controls at Tanner stages 4 and 5 (P <
      or = 0.05). Patients with a grade III varicocele had a significantly smaller left
      testis than controls at each Tanner stage (P < or = 0.05) and significantly
      smaller right testis than controls at Tanner stages 4 and 5 (P < or = 0.05).
      CONCLUSION: The presence of a grade I varicocele in adolescence appears to have
      no effect on normal testicular growth. Some patients with a grade II varicocele
      are at risk of left testicular volume loss with time and should have their
      testicular volume measured annually. Patients with grade III varicocele are at
      risk of bilateral testicular volume loss; a careful evaluation and early surgical
      intervention are recommended in this group of patients.

PMID- 11298041
TI  - The adolescent varicocele. II: the incidence of hydrocele and delayed recurrent
      varicocele after varicocelectomy in a long-term follow-up.
AB  - OBJECTIVE: To determine, in adolescent boys after varicocelectomy, the incidence
      of hydroceles, when they develop and whether the development is procedure
      related. PATIENTS AND METHODS: The records were retrospectively reviewed of 77
      boys who underwent 95 varicocelectomies and had an examination at > or = 6 months
      after surgery. Fifty-six patients underwent a standard Palomo procedure (45 left
      and 11 bilateral) and 21 a modified Ivanissevich repair (14 left and seven
      bilateral). The mean (range) age of the patients at surgery was 14.1 (10-22)
      years and the mean follow-up 25.5 (6-84) months. RESULTS: Of the 67 Palomo
      varicocelectomies 19 (24%) were complicated by hydroceles after surgery, compared
      with four of 28 (14%) Ivanissevich procedures (P = 0.034). Of the Ivanissevich
      repairs, none of the 14 unilateral repairs developed hydroceles. Three hydroceles
      (one bilateral and one left) developed in two of seven patients after bilateral
      varicocelectomy. Of the Palomo repairs, 12 of 45 unilateral repairs were
      complicated by hydroceles, and seven developed in five of 11 patients after
      bilateral varicocelectomy. Although more hydroceles developed after bilateral
      varicocelectomy, there was no significant difference from the unilateral group.
      However, patients who developed hydroceles after bilateral varicocelectomy were
      more likely to require hydrocelectomy (P = 0.013, Fisher's exact test), implying
      that hydroceles developing after bilateral repair tend to be larger. Of the
      hydroceles, two were detected in the first 6 months after surgery, nine at 6-12
      months, three at 13-18 months, five at 19-24 months and four at > 2 years after
      surgery. Three patients had late varicocele recurrence, i.e. 15, 37 and 76 months
      after surgery; these patients had not had varicoceles on palpation after surgery
      at 3, 14 and 63 months, respectively. CONCLUSION: Hydroceles are detected
      infrequently within 6 months of varicocelectomy, with most occurring after 6
      months and even appearing after 3 years. They occur significantly more often
      after a Palomo repair. More hydroceles develop after bilateral repair regardless
      of the technique used, but not significantly so. Because hydroceles often
      develop, a lymphatic-sparing procedure should be used, especially for bilateral
      repair. Recurrent varicoceles may appear as late as 76 months after
      varicocelectomy in patients where none had been detected at a mean of 27 months
      after surgery.

PMID- 11298043
TI  - The use of isosulphan blue to identify lymphatic vessels in high retroperitoneal
      ligation of adolescent varicocele--avoiding postoperative hydrocele.
AB  - OBJECTIVE: To assess whether identifying and preserving the lymphatic vessels,
      using vital dyes, avoids postoperative hydrocele in adolescents with varicocele
      undergoing high retroperitoneal ligation (Palomo procedure). PATIENTS AND
      METHODS: The results were assessed from 28 consecutive adolescent patients
      undergoing varicocelectomy, treated between 1998 and 1999 by the Palomo
      procedure. The lymphatic vessels were identified and preserved using vital dyes,
      to avoid postoperative hydrocele formation. RESULTS: In 24 of the 28 patients
      (86%) the identification and preservation of lymphatic vessels was feasible. Over
      a mean (range) follow-up of 14 (4-24) months there were no postoperative
      hydroceles and no clinical recurrences. CONCLUSION: Identifying and preserving
      the lymphatic drainage of the testis and tunica vaginalis using vital dyes
      prevents the development of postoperative hydrocele in adolescents undergoing the
      Palomo procedure.

PMID- 11298044
TI  - Laparoscopic excision of prostatic utricles in children.
AB  - OBJECTIVE: To report our experience of laparoscopic excision of symptomatic
      prostatic utricles in children. PATIENTS AND METHODS: Prostatic utricles were
      excised laparoscopically in four boys (mean age 6.3 years, range 1.5-17). Cysto
      urethroscopy and cannulation of the prostatic utricle was initially undertaken
      with a cystoscope that was left in situ inside the prostatic utricle to
      facilitate subsequent identification and mobilization during the laparoscopic
      procedure. Laparoscopy was conducted via a 5-mm port inserted through a supra
      umbilical incision. Two more 5 mm working ports were inserted at the right and
      left mid-abdomen. The prostatic utricle was easily identified with the guidance
      of cystoscopic transillumination. Dissection was further facilitated by lifting
      and counter-traction of the prostatic utricle using the indwelling cystoscope.
      The prostatic utricle was completely mobilized and divided at its confluence with
      the urethra using an ultrasonic scalpel. RESULTS: Laparoscopic excision of the
      prostatic utricle was successful in all four patients. The urethral defect was
      closed by intracorporeal suturing in three patients while the defect was small
      enough to be adequately closed by ultrasonic coagulation in one. One patient also
      had a nonfunctioning dysplastic kidney associated with an ectopic ureter joining
      into the prostatic utricle, and underwent nephroureterectomy at the same setting.
      The mean (range) operative duration was 148 (105-225) min. All four patients
      recovered uneventfully with no complications. CONCLUSIONS: Laparoscopic excision
      under cystoscopic guidance is effective for symptomatic prostatic utricles,
      offering a good surgical view and allowing easy dissection in a deep and narrow
      pelvic cavity.

PMID- 11298045
TI  - Retroperitoneoscopic dismembered pyeloplasty for pelvi-ureteric junction
      obstruction in infants and children.
AB  - OBJECTIVE: To report our initial experience of endoscopic dismembered pyeloplasty
      through a retroperitoneal approach in infants and children with pelvi-ureteric
      junction (PUJ) obstruction. PATIENTS AND METHODS: Thirteen infants and children
      with PUJ obstruction underwent retroperitoneoscopic dismembered pyeloplasty (mean
      age at operation 2.7 years, range 0.25-10). Nine patients presented with
      complications secondary to PUJ obstruction, including urinary tract infection,
      pyonephrosis and increasing hydronephrosis with impairment in renal function. The
      other four patients had recurrent loin pain secondary to intermittent PUJ
      obstruction. The patient was placed in semi-prone (for left-sided) or a
      semilateral position (for right-sided PUJ obstruction). The retroperitoneal space
      was entered via a 1-cm incision over the mid-axillary line and further developed
      using a glove balloon. Video-retroperitoneoscopy was undertaken using a 5-mm
      laparoscope. Dismembered pyeloplasty was carried out with the pelvi-ureteric
      anastomosis fashioned using fine polydioxanone sutures over a double-pigtail
      ureteric stent. RESULTS: The retroperitoneoscopic dismembered pyeloplasty was
      successful in 12 patients, while one with previous percutaneous nephrostomy
      drainage for pyonephrosis required open conversion because of difficulties in
      developing the retroperitoneal space. The mean (range) operative duration was 143
      (103-235) min. All patients had a rapid and uneventful recovery. The drainage was
      satisfactory in all 12 patients on a follow-up scan. CONCLUSIONS:
      Retroperitoneoscopic dismembered pyeloplasty is effective and safe in infants and
      young children giving a good early outcome, although the long-term results await
      further studies.

PMID- 11298046
TI  - Laparoscopic partial upper pole nephrectomy in infants and children.
AB  - OBJECTIVE: To retrospectively review 5 years' experience of transperitoneal
      laparoscopic partial nephrectomy (LPN) in infants and children. PATIENTS AND
      METHODS: Between January 1995 and December 1999, 14 upper-pole partial
      nephrectomies (seven right and seven left) were undertaken in 13 children (mean
      age 3.8 years, range 0.4-14). One patient underwent bilateral upper-pole LPN. No
      children required a lower-pole partial nephrectomy during the study period.
      Evaluation included renal ultrasonography, voiding cystourethrography, renal
      scintigraphy and contrast-enhanced computed tomography in some cases. Three ports
      (10, 5 and 5 mm) were used in all except two patients, who required an additional
      2 mm port for liver retraction. The diseased parenchyma was transected with
      electrocautery or harmonic scalpel. The distal ureter was simply transected in
      the absence of reflux, but tied adjacent to the bladder if reflux was present.
      RESULTS: The mean operative duration for LPN was 100 min, with an estimated blood
      loss of < 30 mL. A liquid diet was tolerated on the first morning after surgery
      and age-appropriate regular diet that evening in all except one patient. The mean
      hospital stay was 2.6 days. One patient had a significant decrease in
      haematocrit, which was managed conservatively, not requiring transfusion. Follow
      up telephone interviews with the patients' parents showed that all were satisfied
      with the medical and cosmetic outcome. CONCLUSION: Transperitoneal LPN is
      preferable to open partial nephrectomy because: (i) The magnification provided by
      laparoscopy provides excellent vision for the precise dissection of the
      parenchyma and distal ureter, avoiding injury to the healthy tissue; (ii) There
      is minimal blood loss, fast recovery and less surgical scarring, and when upper
      pole partial nephrectomy is required, LPN is less damaging to the lower-pole.
      Unlike total nephrectomy, where debate remains about open vs laparoscopic
      methods, the specific advantages of LPN make it clearly preferable.

PMID- 11298047
TI  - A comparison of the lateral and posterior retroperitoneoscopic approach for
      complete and partial nephroureterectomy in children.
AB  - OBJECTIVE: To report the comparative results of a selective posterior or lateral
      retroperitoneoscopic approach (RPA) for nephroureterectomy in children. PATIENTS
      AND METHODS: Following an established experience with RPA, 36 complete and 19
      partial nephrouretectomies were prospectively randomized to a posterior and
      lateral retroperitoneoscopic approach The patients were aged 4 months to 14
      years, with a body weight at operation of 5.7-82 kg. For posterior RPA the child
      is positioned prone, with three access ports. The operating space was created
      with balloon dissection and maintained with CO2 insufflation. The child was then
      rotated 30 degrees with the kidney in the dependent position, and the operator
      and assistant standing on the affected side. In the lateral approach the child is
      in the lateral decubitus position with the operator and assistant facing the
      dorsal aspect of the patient. RESULTS: There was no significant difference in
      operative duration between the lateral and posterior approaches for nephrectomy
      (65 and 47 min) or partial nephrectomy (85 and 75 min). Two lateral nephrectomies
      required open conversion (one upper pole and one lower pole). CONCLUSION: The
      posterior approach gives easy and quick access to the renal pedicle. It is
      preferable for complete nephrectomy alone and partial or polar excision. In
      children under 5 years old a near complete ureterectomy can be achieved. The
      lateral approach creates more inferomedial space, gives better access to ectopic
      kidneys and allows complete ureterectomy in all cases. Access to the pedicle in
      the normal position requires more frequent positioning of the kidney. Care must
      be taken as peritoneal tears are more common.

PMID- 11298048
TI  - Laparoscopic retroperitoneal renal and adrenal surgery in children.
AB  - OBJECTIVE: To retrospectively assess the use of a retroperitoneal laparoscopic
      approach for simple nephrectomy and adrenalectomy in children. PATIENTS AND
      METHODS: All retroperitoneal laparoscopic renal and adrenal procedures carried
      out in children and completed between 1993 and March 2000 were reviewed
      retrospectively. Analgesic requirements, hospital stay, complications and blood
      loss were reviewed. The technique is described in detail. RESULTS: Forty-eight
      retroperitoneal laparoscopic procedures were completed in 48 patients (mean age
      5.5 years, range 0.5-16). The procedures included nephrectomy (22),
      nephroureterectomy (15), renal biopsy (six), cyst ablation (two) and simple
      adrenalectomy (three). In all, 11 procedures were undertaken in children aged < 2
      years. Forty-one (91%) of the children undergoing renal procedures were
      discharged in < 24 h. Two patients underwent three adrenalectomies. Two children
      required conversion to open surgery, one undergoing a right-sided adrenalectomy
      and one a nephrectomy. The mean operative duration for nephrectomy and
      nephroureterectomy was 75 min, and for adrenalectomy was 115 min. CONCLUSION:
      Renal and adrenal surgery in children is a safe and rapid procedure with
      retroperitoneal laparoscopy. The operative duration for nephrectomy and
      nephroureterectomy are frequently < 1 h. In addition, laparoscopic surgery offers
      significant advantages in terms of cosmesis and a quicker recovery.

PMID- 11298049
TI  - Endopyelotomy in the symptomatic older child.
AB  - OBJECTIVE: To evaluate the results of endopyelotomy in children, an established
      method in adult practice as a treatment for pelvi-ureteric junction (PUJ)
      obstruction. PATIENTS AND METHODS: Endopyelotomies undertaken between 1992 and
      1999 by one surgeon in an established endourology unit were reviewed
      retrospectively. Children aged > 5 years presenting with pain and obstruction on
      isotope renography were selected for endopyelotomy. Patients with crossing
      vessels detectable on spiral computed tomography were treated by open
      pyeloplasty. Access to the renal pelvis was provided by a uroradiologist.
      Endopyelotomy was carried out through an Amplatz sheath of (median) 26 F. After
      applying traction to invaginate the PUJ an incision was made postero-laterally
      using electrocautery via an 11 F paediatric resectoscope. Stenting was maintained
      for 6 weeks. In all, 13 patients (median age 10 years, range 5-14) were treated;
      two had associated calculi. RESULTS: The symptoms resolved and the obstruction
      was relieved in only six patients, with a median (range) follow-up of 50 (26-68)
      months. The seven patients in whom endopyelotomy failed, as indicated by
      persistent pain, proceeded to open pyeloplasty at a median (range) of 4 (1.3-79)
      months. Of these, two had presented with associated multiple calculi and
      significant hydronephrosis (one with an associated duplex system) and three had
      crossing lower pole vessels at open operation. One developed a urinoma after the
      original endopyelotomy and one had a retained stent fragment removed at the time
      of pyeloplasty. CONCLUSIONS: Endopyelotomy in the symptomatic child requires a
      careful preoperative evaluation. Crossing lower pole vessels warrant an open
      pyeloplasty.

PMID- 11298050
TI  - Correcting chordee without hypospadias and with deficient ventral skin: a new
      technique.

PMID- 11298051
TI  - The 'SANAV' hypospadias dressing.

PMID- 11298052
TI  - Hypospadias: a critical analysis of cosmetic outcomes using photography.
AB  - OBJECTIVE: To analyse the cosmetic outcome of hypospadias surgery using
      photography, rather than the classical assessment by reoperation rate secondary
      to fistula, diverticulum, stenosis and residual penile curvature. PATIENTS AND
      METHODS: The study included 181 consecutive patients with hypospadias who
      underwent surgery between 1997 and 1999. Distal hypospadias (47) was repaired
      using either the 'meatal advancement and glanuloplasty' or the glans
      approximation procedure. Proximal hypospadias (68) was repaired using the onlay
      island-flap technique with preservation of the urethral plate. Penile curvature
      when present was corrected by dorsal plication ( approximately 20%). Two patients
      with perineal hypospadias required a two-stage repair. Complex repeat repairs
      (36) were defined as those patients who had undergone previous surgery 1-7 times
      and required a new urethroplasty by a secondary onlay island-flap technique. The
      follow-up ranged from 6 months to 3 years. Photographs of the penis were taken
      before, immediately and 3-12 months after surgery; these were assessed to
      document objectively the cosmetic outcome. The final photographs were evaluated
      for overall appearance, a mucosal collar, the location and configuration of the
      meatus. The standard was to create a penis that would pass cosmetically as a
      normal circumcised penis. RESULTS: The patients who had chordee without
      hypospadias (15) and fistula repair (13) did not undergo glanuloplasty and
      therefore were not included in the final photographic analysis; this left 153
      patients with follow-up photographs. There were five cases of urethral fistula
      (7%) and one of meatal stenosis (1%) in the proximal group, and three of fistula
      (8%) and two meatal stenosis (6%) in the complex group. The distal group had one
      complication (haematoma) and the two-stage group had no complications. Analysis
      of the photographs showed that most patients had the appearance of a normal
      circumcised penis. Not unexpectedly, the patients who had undergone previous
      surgery had the least satisfactory results (60% appearing normal) compared with
      the proximal and distal groups (76% and 82% appearing normal, respectively).
      CONCLUSIONS: Hypospadias can be repaired safely with few complications in a
      single stage in most patients. Classical complications such as fistula and
      stenosis occur in < 10% of patients, including those undergoing complex
      revisions. Cosmetic outcomes are generally good and photography is an objective
      means to document the appearance.

PMID- 11298053
TI  - Functional evaluation of tubularized-incised plate repair of midshaft-proximal
      hypospadias using uroflowmetry.
AB  - OBJECTIVE: To determine objectively, using uroflowmetry, the functional results
      of the tubularized-incised plate urethroplasty to repair midshaft-proximal
      hypospadias. PATIENTS AND METHODS: Twenty-one patients (mean age 4 years, mean
      follow-up 1.8 years) were selected from those undergoing surgery between January
      1996 and January 1998 at our institution. All patients had midshaft-proximal
      hypospadias and were treated using the Snodgrass technique. Patients were
      included if they were able to void volitionally and had no fistula. The flow
      pattern, maximum (Qmax) and mean flow rate (Qave) were measured; the results were
      expressed as percentiles and compared with published values from normal children.
      The Qmax and Qave were considered normal if > 25th percentile, as equivocally
      obstructed when in the 5-25th percentile and obstructed if < 5th percentile.
      RESULTS: Fourteen patients were considered normal, four as equivocally obstructed
      and three as obstructed. Of the second group, one patient had a urethral
      diverticulum at the native meatus (confirmed by voiding cysto-urethrography) and
      the remaining three patients had meatal stenosis that responded to dilatation,
      with normal flow in two and improvement in the other. Of the obstructed group,
      one patient responded to dilatation and two underwent meatoplasty. CONCLUSION:
      The tubularized-incised plate repair provides satisfactory functional results for
      midshaft-proximal hypospadias; uroflowmetry is an important noninvasive tool to
      evaluate this technique. A long-term follow-up is needed to confirm these
      results.

PMID- 11298054
TI  - Re-operative hypospadias repair using the Snodgrass incised plate urethroplasty.
AB  - OBJECTIVE: To retrospectively assess the results of tubularized incised plate
      (Snodgrass) urethroplasty in a series of re-operative hypospadias repairs in
      children. PATIENTS AND METHODS: The study comprised a follow-up (from 1996 until
      2000) of 13 patients (mean age 7.5 years, range 13 months to 27 years) who had at
      least one previous hypospadias repair and who then underwent a reconstruction
      using the Snodgrass repair. In all cases the urethroplasty was covered with an
      additional layer of subcutaneous tissue. The original location, associated
      complications and results were recorded. In some cases, the long-term follow up
      was conducted by telephone. RESULTS: Associated complications before the
      Snodgrass repair included urethral stricture in two, fistula in three and
      persistent chordee in one patient. The mean (range) follow-up was 22 (9-34)
      months. The cosmetic results were excellent, with two complications (one patient
      with a glans dehiscence and a urethrocutaneous fistula, and a second with meatal
      stenosis). The remaining patients required no further procedures and were voiding
      normally at the last follow-up. CONCLUSION: Excellent cosmetic and functional
      results can be obtained using the Snodgrass incised plate urethroplasty for re
      operative hypospadias repair. Only one patient in this series had an initial
      operation in which the urethral plate was previously incised. Therefore, caution
      should be used when considering an incised plate urethroplasty in these patients.

PMID- 11298055
TI  - Increased incidence of hypospadias in small-for-gestational age infants in a
      neonatal intensive-care unit.
AB  - OBJECTIVE: To identify the incidence of hypospadias in children born prematurely
      and small-for-gestational age (SGA), and to compare this subgroup with infants of
      similar age and weight without hypospadias. PATIENTS AND METHODS: Records from
      the neonatal intensive-care unit (NICU) of a major metropolitan hospital active
      in labour and delivery were reviewed over a 3-year period, specifically examining
      newborns admitted with the diagnosis of SGA, defined as a birth weight of < 10th
      percentile for gestational age. In all, 154 patients were identified and their
      charts reviewed, recording the presence and severity of hypospadias, gestational
      age, birth weight, placental weight, cord length, cord vessels, maternal age,
      parity, multiple births, drug exposure and associated comorbidity. A control
      group of age- and weight-matched infants without hypospadias were also identified
      and compared. RESULTS: Of the 154 patients, 17 (11%) had hypospadias; the
      hypospadias was distal in nine, mid-shaft in four and proximal in four. The
      severity of hypospadias did not correlate with the degree of prematurity or
      weight for gestational age. Placental weight, fetal weight, fetal to placental
      weight ratio and cord length were all lower in the hypospadias group than in the
      control group, but the differences were not statistically significant. The
      maternal age was evenly distributed (median 32 years, range 20-43). Most mothers
      were multiparous and births were multiple in five of 17 (30%). Cryptorchidism
      (three) and inguinal hernia (three) were present in four of the infants.
      CONCLUSIONS: The incidence of hypospadias in SGA infants admitted to the NICU is
      > 10 times higher than that reported for the general population. There was a
      trend to lower placental and fetal weight in SGA infants with hypospadias than in
      the controls. This finding merits further evaluation using a larger population
      database and suggests that factors resulting in SGA infants occur at a critical
      point early in development, affecting both somatic and urethral development.

PMID- 11298056
TI  - Diuretic renography in infants with prenatal unilateral hydronephrosis: an
      explanation for the controversy about poor drainage.
AB  - OBJECTIVE: To present an explanation for impaired drainage on diuretic renography
      in infants with a prenatal diagnosis of unilateral renal pelvic dilatation (RPD)
      who are stable both in terms of renal function and dilatation on follow-up
      investigations, despite undergoing no surgical intervention, and who undergo
      diuretic renography postnatally; this should provide some insight into whether
      impaired drainage is a sign of obstruction in these asymptomatic infants.
      MATERIALS AND METHODS: Using a combination of published studies on the technique
      of diuretic renography and an analysis of such studies, a theoretical model of
      the infant kidney was developed to assess the possibility of prolonged drainage.
      RESULTS: The results from the model showed prolonged drainage in many different
      situations, thus offering an explanation of expected impaired drainage even if
      there was no obstruction. CONCLUSION: Understanding the pathophysiology of
      prenatally diagnosed RPD allows different interpretations of the diuretic
      renogram and may affect the treatment of these children.

PMID- 11298057
TI  - Ontogeny of bladder agenesis in rats induced by adriamycin.
AB  - OBJECTIVES: To determine the anatomical steps leading to bladder agenesis in rats
      prenatally exposed as fetuses on gestational days (GD) 6-9 to adriamycin.
      MATERIALS AND METHODS: Timed-pregnant Sprague-Dawley rats were injected
      intraperitoneally with adriamycin at 2 mg/kg (n = 28) on GD 6-9 (vaginal plug =
      day 0). The control group (n = 21) received saline. Fetuses were harvested on GD
      10, 11, 12, 13, 14, 15 and 16. Serial paraffin sections were prepared from a
      minimum of 10 experimental and five control fetuses at each gestational age, and
      stained with either trichrome or haematoxylin and eosin, and examined by light
      microscopy. RESULTS: In the control group the urorectal septum first became
      visible and the mesonephric ducts apparently abutting the anterior cloaca on GD
      12. The presumptive urinary bladder was clearly defined on GD 14. On GD 15, the
      common excretory ducts became incorporated into the newly formed urogenital sinus
      and the ureters opened into the bladder. In the treated animals, beginning on GD
      11, the undivided cloaca was noticeably smaller and by GD 13-14, the vesical
      extension of the urogenital sinus was conspicuously absent. Instead, opposite
      ureters joined to drain directly into the proximal blind-ending urethra or the
      persistent distal urogenital sinus. CONCLUSIONS: Prenatal exposure of rat fetuses
      to adriamycin resulted in primary agenesis rather than secondary resorption of
      the bladder. The ontogeny showed that the mechanism underpinning bladder
      development is unique and is under the influence of factors that can be targeted
      by adriamycin. Further work will elucidate the unique nature of bladder
      organogenesis and should have important applications in future research into
      artificial bladders.

PMID- 11298058
TI  - The renal-resistive index from the last 3 months of pregnancy to 6 months old.
AB  - OBJECTIVE: To measure the renal resistive index (RI, an estimate of renal
      vascular resistance, used to assess upper tract obstructive uropathy) from the
      last trimester of pregnancy to the sixth month of life in a large series of
      healthy subjects, and thus to identify normal values that can be used routinely.
      During the first semester of life significant haemodynamic changes during the
      physiological development of the kidney cause considerable variability in RI,
      which is thus considered less reliable in this period. SUBJECTS AND METHODS: From
      September 1998 to October 1999, 93 subjects (186 renal units, RU) were enrolled;
      32 were fetuses in the last trimester of pregnancy (group 1, 64 RU) and 61 were
      children (122 RU), 30 aged 0-1 month (group 2, 60 RU), 20 aged 1-3 months (group
      3, 40 RU) and 11 aged 3-6 months (group 4, 22 RU). All subjects underwent colour
      Doppler ultrasonography and the RI of the renal artery was measured for each
      kidney. RESULTS: The RI was very high in group 1 but decreased noticeably during
      the first 6 months of life, reaching values similar to those in adults after the
      third month. The variability in RI continuously declined with age, becoming less
      important. The normal ranges for groups 1-4 were 0.67-0.88, 0.57-0.90, 0.60-0.84
      and 0.65-0.75, respectively. There were no statistically significant differences
      between the left and right kidneys. CONCLUSION: In the first semester of life
      there is more than one landmark value of RI depending on the month of age of the
      infant. This should be considered when assessing upper tract obstructive
      uropathies after birth and the RI should be compared with the normal ranges
      reported herein.

PMID- 11298059
TI  - The development of the external urethral sphincter in humans.
AB  - OBJECTIVE: To assess the hypothesis that during fetal development, the external
      urethral sphincter changes from a concentric sphincter of undifferentiated muscle
      fibres to a transient ring of striated muscle which regresses caudo-cranially in
      the posterior urethra during the first year of life, when the sphincter assumes
      its omega-shaped configuration. MATERIALS AND METHODS: The anatomy and
      development of the external urinary sphincter was assessed in human males and
      females during fetal life. Plastic-embedded sections (transverse, sagittal and
      frontal planes; 300-700 microm) of the pelvis of 31 females and 31 males (9 weeks
      of gestation to newborn) were stained with azure II/methylene blue/basic fuchsin
      and viewed at x 4-80. The sections of interest were taken from the bladder neck
      to the perineum. The sections of the membranous urethra were reconstructed three
      dimensionally using a computer program. RESULTS: In both male and female an omega
      shaped external sphincter was apparent in all specimens at > 10 weeks of
      gestation. In the early fetal period (ninth week), there was undifferentiated
      mesenchyme; in this period the mesenchyme was more dense in the anterior part and
      loose in the posterior part of the urethra. In females, there was a close
      connection between the urethra and the anterior wall of the vagina. CONCLUSION:
      The omega-shaped configuration of the external urethral sphincter was
      recognisable from 10 weeks of gestation in both sexes. There was no suggestion of
      a change from a cylindrical to an omega-shaped sphincter in the fetal period to
      birth. Also, a transient 'tail' posterior to the sphincter was not apparent. The
      rectovesical septum was well developed in neonates. There is no reason to assume
      that the development of the septum leads to an apoptosis of muscle cells in the
      posterior part of the external sphincter in males after birth. The anatomical
      development of the external sphincter does not explain transient outlet
      obstruction during fetal life. The function of the muscle may change during
      development because of neuronal maturation.

PMID- 11298060
TI  - The overactive bladder in children: a potential future indication for
      tolterodine.
AB  - OBJECTIVE: To determine the safety, efficacy and pharmacokinetics of tolterodine
      in children with an overactive bladder. PATIENTS AND METHODS: Thirty-three
      children (20 boys and 13 girls, aged 5-10 years) with an overactive bladder and
      symptoms of urgency, frequency and/or urge incontinence were enrolled in an open,
      dose-escalation study. Patients were treated with oral tolterodine 0.5 mg (n =
      11), 1 mg (n = 10) or 2 mg (n = 12) twice daily for 14 days. The primary safety
      endpoint was the change in residual urinary volume, as determined by
      ultrasonography. In addition, voiding diary variables (frequency and incontinence
      episodes) and pharmacokinetics were evaluated. Other safety endpoints included
      laboratory variables, electrocardiogram recordings and reported adverse events.
      RESULTS: There were no safety concerns in terms of the change in residual urinary
      volume for any of the three dosage groups; values were comparable with baseline
      after 2 weeks of treatment for all three dosages. Adverse events were reported by
      20 patients (six on 0.5 mg, five on 1 mg, and nine on 2 mg). Most adverse events
      were not considered to be drug-related; of the 13 possibly related events, 10
      occurred in those taking 2 mg. Headache was the most commonly reported adverse
      event. No serious adverse events were reported and there were no general safety
      concerns. There was an improvement in voiding diary variables in all treatment
      groups after 2 weeks of treatment, although the efficacy was greatest in those
      taking 1 mg and 2 mg. Pharmacokinetic findings were consistent with dose
      linearity over the range 0.5-2 mg. CONCLUSION: The results support the use of 1
      mg twice daily as the optimal dose of tolterodine for treating children aged 5-10
      years with an overactive bladder.

PMID- 11298061
TI  - One thousand video-urodynamic studies in children with non-neurogenic bladder
      sphincter dysfunction.
AB  - OBJECTIVE: To ascertain the aetiology and epidemiology of non-neurogenic bladder
      sphincter dysfunction (NNBSD) by assessing the results of prospective video
      urodynamic studies (VUD) in 1000 children. PATIENTS AND METHODS: During a 4-year
      study period (January 1995 to December 1998) 1000 children prospectively
      underwent VUD to further define their NNBSD. After a noninvasive screening
      assessment consisting of a history, voiding diary, clinical examination, urine
      analysis, ultrasonography and uroflowmetry, those children who would benefit from
      further VUD were selected. The selection criteria included a history of urinary
      tract infection (UTI), a small bladder capacity not responding to training,
      dysfunctional uroflow, ultrasonographic abnormalities and resistance to therapy.
      During the study period 3500 children were screened for incontinence problems,
      including monosymptomatic nocturnal enuresis; 1000 of these were selected for VUD
      (524 boys and 476 girls). RESULTS: The urodynamic diagnosis was of normal bladder
      sphincter function in 62 (6.2%, male : female 44 : 56), urge syndrome in 582
      (58%, 58 : 42), dysfunctional voiding in 316 (32%, 49 : 51) and 'lazy bladder' in
      40 (4%, 20 : 80). Boys diagnosed with a 'lazy bladder' were younger than those
      with urge syndrome and dysfunctional voiding. Girls with dysfunctional voiding
      were younger than those with urge syndrome. The incidence of UTI was
      significantly higher in girls than in boys; boys with NNBSD had no greater risk
      for UTI and in girls the general risk was 34%. Only in girls with a lazy bladder
      was there a significantly higher incidence of UTI (53%). Reflux occurred equally
      in all groups, with an overall incidence of 15%. The incidence of obstipation was
      significantly higher in girls with a lazy bladder, and overall was 17%.
      CONCLUSION: These results from a large series provide a new insight into the
      epidemiology and pathophysiology of NNBSD. The age distribution provides evidence
      against a dysfunctional voiding sequence. The risk of developing UTI in NNBSD is
      greater only in girls. In children with a lazy bladder the risk is also
      significantly higher, indicating that residual urine is a greater risk factor
      than detrusor instability. Urge syndrome and dysfunctional voiding in girls carry
      the same risk for developing UTI, indicating that bladder instability is a higher
      risk factor for UTI than detrusor sphincter discoordination. All dysfunctions
      carry an equal risk for developing secondary reflux. Children with NNBSD have
      different primary diseases but all have a common risk of incontinence, UTIs,
      reflux and obstipation.

PMID- 11298062
TI  - High-pressure bladder: an underlying factor mediating renal damage in the absence
      of reflux?
AB  - OBJECTIVE: To assess urodynamic studies of children with nonrefluxing
      pyelonephritis, investigate the possible connection between renal damage (as
      approximately 40% of children with febrile urinary tract infections and no
      evidence of vesico-ureteric reflux have irreversible renal cortical scarring) and
      lower urinary tract dysfunction, to test the hypothesis that bladders with high
      storage and voiding pressures may be the cause of renal damage in these patients.
      PATIENTS AND METHODS: The clinical records and urodynamic studies of 52 children
      (46 girls and six boys, mean age 6.6 years) with febrile urinary infections, no
      evidence of reflux and photopenic areas on renal scintigraphy were evaluated
      retrospectively. Each child was evaluated by urinary ultrasonography, a voiding
      cystogram, 99mTc-dimercaptosuccinic acid (DMSA) scan and urodynamic studies. The
      storage phase of the urodynamic study was divided into two equal segments to
      consider the filling variables of each. During the emptying phase, voiding
      pressures and voiding pressures with reference to peak detrusor contraction were
      evaluated. RESULTS: Despite no child having reflux, the DMSA scans showed
      bilateral renal scarring in 39 (75%) and unilateral scarring in the remaining
      children. Forty-eight (93%) children had abnormal urodynamic values: high filling
      pressures (34), high-pressure uninhibited contractions (32), high voiding
      pressures (31) and discoordinated voiding (28). The cystometric bladder capacity
      was lower than the expected bladder capacity (- 75 mL) in 82% of the patients; in
      only four patients were the urodynamics considered normal. CONCLUSIONS: Most
      children with renal scarring and no reflux had lower urinary tract dysfunction.
      Common findings include high storage and voiding pressures, and discoordinated
      voiding. These findings suggest that abnormal bladder dynamics play a role in the
      development of renal scars that occur in the absence of reflux.

PMID- 11298064
TI  - The genetics of type 2 diabetes.

PMID- 11298065
TI  - Anti-TNF agents for rheumatoid arthritis.

PMID- 11298066
TI  - The pharmacokinetics of methadone in HIV-positive patients receiving the non
      nucleoside reverse transcriptase inhibitor efavirenz.
AB  - AIMS: Methadone is predominantly metabolized by cytochrome P450 3A4 and the non
      nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is a recognized
      inducer of this enzyme. We evaluated the pharmacokinetics of methadone in the
      presence and absence of efavirenz when administered to HIV infected patients with
      a history of injection drug use (IDU). METHODS: Eleven patients on stable
      methadone maintenance therapy, due to commence antiretroviral therapy (ART),
      participated in this study. Steady state methadone kinetic profiles were obtained
      on two occasions 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h post dosing. Following
      centrifugation, separated plasma was heated at 58 degrees C for 30 min to
      inactivate HIV and stored at -80 degrees C until methadone analysis by high
      performance liquid chromatography. RESULTS: When combined with efavirenz there
      was a marked decrease in the maximum plasma concentration (Cmax) of methadone
      from 689 (range 212-1568) to 358 (range 205-706) ng ml(-1), P = 0.007 : 95%
      confidence interval (CI) 112-549. The mean area under the methadone concentration
      curve 0-24 h (AUC(0,24 h)) was also significantly reduced from 12341 (range 3682
      34147) to 5309 (range 2430-10349) ng ml(-1) h in the presence of efavirenz, P =
      0.012 : 95% CI 1921-12143. Nine patients described symptoms of methadone
      withdrawal and received a dose increase. Although methadone AUC(0,24 h) was
      reduced by over 50% following efavirenz the mean increase in methadone dose
      required was 22% (range 15-30 mg). CONCLUSION: The inclusion of the NNRTI
      efavirenz in once daily ART for HIV patients with a history of IDU receiving
      methadone maintenance results in a significant reduction in methadone plasma
      concentrations mediated by enzyme induction. It is important to distinguish
      efavirenz neurological effects which were observed between days 1-5 of therapy
      from symptoms of methadone withdrawal which occurred from day 8 onwards. The dose
      of methadone was adjusted by increments of 10 mg to counteract the efavirenz
      inducing effect.

PMID- 11298067
TI  - Responsiveness of human varicose saphenous veins to vasoactive agents.
AB  - AIMS: To test in vitro the constrictor and relaxation responsiveness of variously
      diseased segments of human saphenous vein from patients with varicose vein
      disease. METHODS: The vein segments were derived (i) from the inguinal saphenous
      vein (valvularly incompetent and slightly dilated; tissue A); (ii) from the
      distal end of the lower leg just above the medial ankle (competent; tissue B);
      (iii) from a tributary to the long saphenous vein just below the knee (dilated,
      incompetent and overtly varicose; tissue C). The contractile responses were
      tested with phenylephrine (an alpha-adrenergic receptor agonist) and aescin, a
      clinically used phlebotonic drug derived from horse chestnut extract. Relaxant
      responses were tested with acetylcholine and sodium nitroprusside. RESULTS: Both
      contractile agents contracted vein segments from the inguinal and ankle area with
      similar potency and efficacy, but were virtually without effect in the overtly
      varicose segments from the calf. EC50 values (molar concentration of the agonist
      that produces 50% of the maximum effect) in tissues A and B were 2.9 +/- 0.3 and
      2.5 +/- 0.5 micromol l(-1) (phenylephrine) and 9.4 +/- 1.0 and 15.9 +/- 2.5
      micromol l(-1) (aescin); the corresponding maximum effects (maximum effect,
      percent of KCl-induced contraction) were 76 +/- 3 and 70 +/- 4% (phenylephrine)
      and 70 +/- 2 and 71 +/- 3% (aescin) (P = NS in both cases for A vs B). In tissue
      C, the maximum effects were 5 +/- 5% (phenylephrine) and 10 +/- 7% (aescin) of
      KCl-induced contraction (not significantly different from zero). Acetylcholine
      induced relaxation was similar for vein segments from locations A and B, whereas
      sodium nitroprusside was more effective in tissue B than A. CONCLUSIONS: These
      findings support the notion that abnormalities within the venous wall affect
      venous smooth muscle contractility. Since competent and incompetent clinically
      normal vessels show normal contractile responses, whereas varicose vessels are
      not responsive to vasoactive drugs, it is likely that pharmacological treatment
      regimens are effective in early, but not in late stages of the disease.

PMID- 11298068
TI  - Assessment of forearm vasodilator responses to acetylcholine and albuterol by
      strain gauge plethysmography: reproducibility and influence of strain gauge
      placement.
AB  - AIMS: To determine the within-subject reproducibility of the forearm blood flow
      response to acetylcholine and the beta2-adrenoceptor agonist albuterol as
      measured by strain gauge plethysmography. To examine the influence of strain
      gauge placement on these responses. METHODS: Vasodilator response to brachial
      artery infusion of drugs was assessed by strain gauge plethysmography in six
      healthy men on each of three occasions separated by 1 week. Strain gauges were
      placed on both arms at the point of maximum diameter. On the infused arm two
      further gauges were positioned approximately 4 cm proximal and distal to the
      middle gauge. RESULTS: Within-subject coefficients of variation (WCV) of absolute
      blood flow responses for each dose of acetylcholine (7.5, 15, 30 micrograms min(
      1)) ranged from 24% to 27%, as compared with WCV values of 41% to 62% for the
      percentage changes in blood flow ratio (infused : noninfused arm). For albuterol
      (0.3, 1, 3 micrograms min(-1)) the corresponding WCV values were 16% to 19% and
      30% to 55% for absolute blood flow and percentage change in blood flow ratio,
      respectively. WCV for the area under dose-response curve (AUC) for absolute blood
      flow was 18% and 13% for acetylcholine and albuterol, respectively. Vasodilator
      responses were similar whether recorded proximal to or at the point of maximal
      forearm circumference. Distal strain gauge misplacement underestimated responses
      and the difference was greater for acetylcholine than for albuterol. CONCLUSIONS:
      In healthy men, the WCV for responses expressed as absolute blood flow, to
      acetylcholine and albuterol ranges from 16% to 27%.

PMID- 11298069
TI  - Stereoselective halofantrine disposition and effect: concentration-related QTc
      prolongation.
AB  - AIMS: 1) To characterize the variability of multiple-dose halofantrine
      pharmacokinetics over time in healthy adults, 2) to correlate the pharmacodynamic
      measure electrocardiographic (ECG) QT interval with (+)- and (-)-halofantrine
      plasma concentration and 3) to evaluate the safety and tolerance of halofantrine
      hydrochloride given over time to healthy adults. METHODS: Twenty-one healthy
      subjects were enrolled and 13 completed the study (180 days). Subjects received
      either 500 mg of racemic halofantrine once daily in the fasted state for 42 days,
      or placebo, and then halofantrine washout was documented for the following 138
      days. Pharmacokinetic and pharmacodynamic (ECG QTc) measurements were obtained.
      RESULTS: Mean accumulation half-times (days) for halofantrine were: 7.0 +/- 4.8
      [(+)-halofantrine] and 7.3 +/- 4.8 [(-)-halofantrine]. Mean steady-state
      concentrations were: 97.6 +/- 52.0 ng ml(-1) [(+)-halofantrine] and 48.5 +/- 20.8
      [(-)-halofantrine]. Steady-state oral clearance was: 139 +/- 73 l h(-1) [(+)
      halofantrine] and 265 +/- 135 l h(-1) [(-)-halofantrine]. Peak plasma
      concentrations of both (+)- and (-)-halofantrine were attained at 6 h and maximal
      ECG QTc prolongation was at 4-8 h following drug administration. Fourteen of 16
      subjects who received active drug had ECG QTc prolongation that was positively
      correlated with both (+)- and (-)-halofantrine concentration. The five subjects
      who received placebo had no demonstrable change in ECG QTc throughout the study.
      Conclusions Halofantrine accumulates extensively and shows high intersubject
      pharmacokinetic variability, is associated with concentration-related ECG QTc
      prolongation in healthy subjects, and is clinically well tolerated in this
      subject group.

PMID- 11298070
TI  - Identification of the cytochrome P450 enzymes involved in the N-demethylation of
      sildenafil.
AB  - AIMS: To characterize the cytochrome P450 (CYP) enzymes responsible for the N
      demethylation of sildenafil to its main metabolite, UK-103 320, to investigate
      the potential inhibitory effects of sildenafil on CYP enzymes and to evaluate the
      potential of selected drugs to affect sildenafil metabolism. METHODS: The
      metabolic pathways of sildenafil N-demethylation were studied using human liver
      microsomes, as well as microsomes expressing individual human CYP enzymes.
      Further studies to identify the individual enzymes were performed at 2.5 and 250
      microM sildenafil, and employed a combination of chemical inhibition, correlation
      analysis, and metabolism by expressed recombinant CYP enzymes. In addition, the
      effect of sildenafil on the activity of the six major drug metabolizing enzymes
      was investigated. RESULTS: Sildenafil conversion was found to be mediated by at
      least two CYP enzymes, for which the mean kinetic parameters were Km1 = 6(+/-3
      microM), Km2 = 81(+/-45 microM), Vmax1 = 22(+/-9 pmol) and Vmax2 = 138(+/-77
      pmol) UK-103 320 formed min(-1) mg(-1). At 250 microM sildenafil, N-demethylation
      was primarily mediated through the low-affinity, high-Km enzyme (approximately
      83%), whilst at 2.5 microM there was a greater role for the high-affinity, low-Km
      enzyme (approximately 61%). Ketoconazole strongly inhibited metabolism at both
      sildenafil concentrations and was the only significant inhibitor at 250 microM
      sildenafil. At the lower sildenafil concentration, sulphaphenazole and quinidine
      also inhibited formation of UK-103 320. Overall, 75% or more of the N
      demethylation of sildenafil at any concentration is probably attributable to
      CYP3A4. These results were supported by experiments using expressed human CYP
      enzymes, in which only CYP3A4 and CYP2C9 exhibited substantial sildenafil N
      demethylase activity (respective Km values of 221 microM and 27 microM).
      Sildenafil metabolism was inhibited by potent CYP3A4 inhibitors which are used
      clinically, but was found to be only a weak inhibitor of drug metabolizing
      enzymes itself, the strongest inhibition occurring against CYP2C9 (Ki = 80
      microM). CONCLUSIONS: Evidence is provided for CYP3A4 and to a lesser extent
      CYP2C9-mediated metabolism of sildenafil. There is the possibility that elevated
      plasma concentrations of sildenafil could occur with coadministration of known
      inhibitors of CYP2C9 or CYP3A4. Since peak plasma concentrations of clinical
      doses of sildenafil are only 200 ng ml(-1) ( approximately 0.4 microM) it is very
      unlikely that sildenafil will significantly alter the plasma concentration of
      other compounds metabolized by cytochrome P450 enzymes.

PMID- 11298071
TI  - Evaluation of a pharmacokinetic interaction between remacemide hydrochloride and
      phenobarbitone in healthy males.
AB  - AIMS: To determine whether there is a pharmacokinetic interaction between the
      antiepileptic drugs remacemide and phenobarbitone. METHODS: In a group of 12
      healthy adult male volunteers, the single dose and steady-state kinetics of
      remacemide were each determined twice, once in the absence and once in the
      presence of phenobarbitone. The effect of 7 days remacemide intake on initial
      steady-state plasma phenobarbitone concentrations was also investigated. RESULTS:
      Apparent remacemide clearance (CL/F) and elimination half-life values were
      unchanged after 7 days intake of the drug in the absence of phenobarbitone (1.25
      +/- 0.32 vs 1.18 +/- 0.22 l kg(-1) h(-1) and 3.29 +/- 0.68 vs 3.62 +/- 0.85 h,
      respectively). Concomitant administration of remacemide with phenobarbitone
      resulted in an increase in the estimated CL/F of remacemide (1.25 +/- 0.32 vs
      2.09 +/-0.53 l kg-1 h-1), and a decreased remacemide half-life (3.29 +/- 0.68 vs
      2.69 +/- 0.33 h). The elimination of the desglycinyl metabolite of remacemide
      also appeared to be increased after the phenobarbitone intake (half-life 14.72 +/
      2.82 vs 9.61 +/- 5.51 h, AUC 1532 +/- 258 vs 533 +/- 281 ng ml(-1) h). Mean
      plasma phenobarbitone concentrations rose after 7 days of continuing remacemide
      intake (12.67 +/- 1.31 vs 13.86 +/- 1.81 microgram ml(-1)). CONCLUSIONS:
      Phenobarbitone induced the metabolism of remacemide and that of its desglycinyl
      metabolite. Remacemide did not induce its own metabolism, but had a modest
      inhibitory effect on the clearance of phenobarbitone.

PMID- 11298072
TI  - Outcomes of a randomized controlled trial of a clinical pharmacy intervention in
      52 nursing homes.
AB  - AIMS: To evaluate whether a year long clinical pharmacy program involving
      development of professional relationships, nurse education on medication issues,
      and individualized medication reviews could change drug use, mortality and
      morbidity in nursing home residents. METHODS: A cluster randomised controlled
      trial, where an intervention home was matched to three control homes, was used to
      examine the effect of the clinical pharmacy intervention on resident outcomes.
      The study involved 905 residents in 13 intervention nursing homes and 2325
      residents in 39 control nursing homes in south-east Queensland and north-east New
      South Wales, Australia. The outcome measures were: continuous drug use data from
      government prescription subsidy claims, cross-sectional drug use data on
      prescribed and administered medications, deaths and morbidity indices
      (hospitalization rates, adverse events and disability indices). RESULTS: This
      intervention resulted in a reduction in drug use with no change in morbidity
      indices or survival. Differences in nursing home characteristics, as defined by
      cluster analysis with SUDAAN, negated intervention-related apparent significant
      improvements in survival. The use of benzodiazepines, nonsteroidal anti
      inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was
      significantly reduced in the intervention group, whereas the use of digoxin and
      diuretics remained similar to controls. Overall, drug use in the intervention
      group was reduced by 14.8% relative to the controls, equivalent to an annual
      prescription saving of A64 dollars per resident (approximately 25 pound
      sterling). CONCLUSIONS: This intervention improved nursing home resident outcomes
      related to changes in drug use and drug-related expenditure. The continuing
      divergence in both drug use and survival at the end of the study suggests that
      the difference would have been more significant in a larger and longer study, and
      even more so using additional instruments specific for measuring outcomes related
      to changes in drug use.

PMID- 11298073
TI  - Patterns of prescription and drug use in ophthalmology in a tertiary hospital in
      Delhi.
AB  - AIMS: The present study was carried out to describe the patterns of prescription
      and drug use in Ophthalmology in out-patients at Dr Rajendra Prasad (R.P.) Centre
      for Ophthalmic Sciences of All India Institute of Medical Sciences (A.I.I.M.S.),
      New Delhi. METHODS: Prescriptions of 1017 out-patients were audited through a
      specially designed form and analysed for the following: average number of drugs
      per prescription, duration of treatment (recorded or not), dosage forms
      prescribed, frequency of administration (recorded or not), number of encounters
      with antibiotics and percentage of drugs prescribed by generic name. RESULTS:
      Prescription analysis showed that the average number of drugs per prescription
      was 3.03. Duration of treatment was recorded for only 26.4% of the drugs
      prescribed. The maximum number of drugs prescribed were in the form of eye drops
      (76%), followed by tablets (10.9%), ointments (6.4%), syrups (1%), capsules
      (0.7%), lotions (0.3%) and injections (0.1%). No dosage form was recorded for
      4.6% of the drugs prescribed. The frequency of administration was recorded for
      only 77.9% of the drugs prescribed. The number of antibiotics prescribed was 1059
      which constitutes 34.2% of the total number of drugs prescribed. The percentage
      of drugs prescribed by generic name was only 35%. CONCLUSIONS: The results
      obtained in this study indicated an awareness of polypharmacy but a high
      incidence of common prescription writing errors such as not recording the
      duration of therapy, frequency of administration and dosage form. Moreover
      prescribing by generic name was also low.

PMID- 11298074
TI  - Sudden unexpected death in infants under 3 months of age and vaccination status- 
      a case-control study.
AB  - AIMS: To determine whether DTPP+Hib vaccination (diphtheria, tetanus, pertussis,
      poliomyelitis +/- haemophilus) increased the risk of sudden unexpected death
      (SUD) in children under 3 months of age. METHODS: We conducted a multicentre case
      control study in the 28 French 'SIDS Centers'. Case selection was based on death
      labelled sudden infant death syndrome (SIDS) of an infant aged between 30 and 90
      days. Three living controls were selected, matched for sex, gestational age and
      born immediately after the victim in the same maternity unit. RESULTS: We
      identified 114 cases of SUD aged between 30 and 90 days and 341 live controls
      matched for age and sex and born in the same maternity unit as the case. DTPP+/
      Hib immunization did not increase the risk of SUD (OR 1.08) (95% CI 0.49, 2.36)
      in children under 3 months of age when adjusted for sleeping position, illness in
      the week before death, maternal tobacco consumption, birth weight, type of
      mattress, breastfeeding and sex. However, low birth-weight (6.53 [2.29, 18.9]),
      multiple birth (5.1 [1.76, 15.13]), no breastfeeding (1.77 [1.1, 2.85]), prone
      sleeping position (9.8 [5, 8, 18, 9]), soft mattress (3.26 [1.69, 6.29]), recent
      illness (3.44 [1.84, 6.41]) and parental smoking (1.74 [1.2, 2.96]) were
      confirmed as risk factors in early SIDS. CONCLUSIONS: DTPP+/-Hib immunization is
      not a risk factor for early SUD. In this population, we found the same risk
      factors as described for SIDS.

PMID- 11298075
TI  - Frequency of cytochrome P450 2C9 mutant alleles in a Korean population.
AB  - AIMS: To determine the frequencies of CYP2C9 variants in the Korean population
      and compare them with the frequencies in other ethnic populations. METHODS:
      Genotyping of CYP2C9*2 and CYP2C9*3 allelic variants was carried out in 574
      Korean subjects by PCR and restriction fragment length pattern analysis. RESULTS:
      Thirteen of 574 subjects (2.3%) were heterozygous for CYP2C9*3 (Ile359Leu), but
      no subjects with a CYP2C9*2 allele or homozygous for CYP2C9*3 were identified.
      The allele frequency of CYP2C9*3 in Korean subjects (0.0113, 95% CI 0.0066
      0.0193) was similar to that of other East Asian populations, but was considerably
      lower than that of Caucasian populations. CONCLUSIONS: CYP2C9*3 seems to be an
      allelic variant related to the functional polymorphism of CYP2C9, but this
      variant is rarely seen among Koreans compared with Caucasians. Routine genotyping
      of the CYP2C9*2 allele is considered to be unnecessary in Korean and East Asians,
      because this allele appears to be extremely rare or absent in these populations.

PMID- 11298076
TI  - Involvement of human liver cytochrome P4502B6 in the metabolism of propofol.
AB  - AIMS: To determine the cytochrome P450 (CYP) isoforms involved in the oxidation
      of propofol by human liver microsomes. METHODS: The rate constant calculated from
      the disappearance of propofol in an incubation mixture with human liver
      microsomes and recombinant human CYP isoforms was used as a measure of the rate
      of metabolism of propofol. The correlation of these rate constants with rates of
      metabolism of CYP isoform-selective substrates by liver microsomes, the effect of
      CYP isoform-selective chemical inhibitors and monoclonal antibodies on propofol
      metabolism by liver microsomes, and its metabolism by recombinant human CYP
      isoforms were examined. RESULTS: The mean rate constant of propofol metabolism by
      liver microsomes obtained from six individuals was 4.2 (95% confidence intervals
      2.7, 5.7) nmol min(-1) mg(-1) protein. The rate constants of propofol by
      microsomes were significantly correlated with S-mephenytoin N-demethylation, a
      marker of CYP2B6 (r = 0.93, P < 0.0001), but not with the metabolic activities of
      other CYP isoform-selective substrates. Of the chemical inhibitors of CYP
      isoforms tested, orphenadrine, a CYP2B6 inhibitor, reduced the rate constant of
      propofol by liver microsomes by 38% (P < 0.05), while other CYP isoform-selective
      inhibitors had no effects. Of the recombinant CYP isoforms screened, CYP2B6
      produced the highest rate constant for propofol metabolism (197 nmol min-1 nmol
      P450-1). An antibody against CYP2B6 inhibited the disappearance of propofol in
      liver microsomes by 74%. Antibodies raised against other CYP isoforms had no
      effect on the metabolism of propofol. CONCLUSIONS: CYP2B6 is predominantly
      involved in the oxidation of propofol by human liver microsomes.

PMID- 11298077
TI  - The insulin hypoglycaemia test for the assessment of the hypothalamic--pituitary-
      adrenal function.

PMID- 11298078
TI  - Central precocious puberty and occult intracranial tumours.

PMID- 11298079
TI  - Central precocious puberty: clinical and laboratory features.
AB  - OBJECTIVE: To determine whether the initial presentation of patients with central
      precocious puberty (CPP) varies according to the aetiology, whether this permits
      the differentiation between idiopathic and organic forms, and whether the body
      mass index (BMI) and plasma leptin concentrations are linked to gonadotrophin
      secretion. DESIGN: The clinical and laboratory features of 256 patients (26 boys
      and 230 girls) with CPP were studied separately in boys and girls. We compared
      patients with idiopathic CPP (seven boys and 186 girls) to those with organic
      CPP, whose pubertal development revealed a central nervous system (CNS) lesion
      (five boys and 11 girls), and to patients with organic CPP associated with a
      previously treated CNS lesion (14 boys and 33 girls). RESULTS: Boys with organic
      CPP, having revealed or treated CNS lesions, started their puberty earlier (3.0
      +/- 1.0 years and 6.7 +/- 0.5 years) than boys with idiopathic CPP (8.5 +/- 0.2
      years, P < 0.01 and < 0.05). Boys with organic CPP associated with a treated CNS
      lesion had lower luteinizing hormone (LH)/follicle stimulating hormone (FSH)
      peaks ratio after stimulation with gonadotrophin releasing hormone (GnRH) (1.6 +/
      0.5) than did boys with idiopathic CPP (2.2 +/- 0.3, P < 0.05). Girls with
      organic CPP revealing a CNS lesion started their puberty earlier (3.6 +/- 0.9
      years) than girls with idiopathic CPP (6.6 +/- 0.1 years, P < 0.0 l) and had
      higher LH (P < 0.01) and FSH peaks (< 0.05). Girls with organic CPP associated
      with a treated CNS lesion had higher BMI (1.8 +/- 0.2 z-score) than did girls
      with idiopathic CPP (1.3 +/- 0.1 zs, P < 0.05), higher leptin concentrations
      (11.7 +/- 1.8 microg/l vs. 7.7 +/- 0.5 microg/l, P < 0.0 l), LH peak (P < 0.01),
      FSH peak (P < 0.05) and LH/FSH peaks ratio (1 +/- 0.1 vs. 0.8 +/- 0.1, P < 0.05).
      Only 12.4% of the girls with idiopathic CPP had BMI-zs < 0, and their plasma
      leptins were positively correlated with BMI (P < 0.0001). CONCLUSIONS: The
      features of central precocious puberty vary according to the aetiology, but it is
      impossible to exclude a central nervous system lesion in a given patient with
      central precocious puberty without performing central nervous system imaging.
      This imaging remains necessary in all cases of central precocious puberty. Most
      of the girls with idiopathic central precocious puberty had increased BMI, but we
      found no correlation between plasma leptin concentrations and gonadotrophin
      secretion.

PMID- 11298080
TI  - The effect of the menopause on prolactin levels in patients with
      hyperprolactinaemia.
AB  - OBJECTIVE: Microprolactinomas have been reported to resolve spontaneously after
      pregnancy and there have been suggestions that oestrogen therapy increases the
      size of microprolactinomas. Little is known, however, about the effect of the
      menopause in patients previously known to be hyperprolactinaemic. The aim of this
      study was to find out if pregnancy or the menopause leads to an alteration in
      prolactin levels. DESIGN: We conducted a retrospective study of 148 case notes of
      patients with hyperprolactinaemia and microprolactinomas treated at the Radcliffe
      Infirmary during the period 1976-96. Sixty-nine female patients who had not had
      pituitary surgery as treatment for microprolactinoma were used as a control
      group. None of this group became pregnant or reached the menopause. They were
      compared with 25 female patients who became pregnant, 11 who became menopausal
      and 11 who were male. Subjects were excluded from the analysis if there were no
      follow-up data off dopamine agonist treatment or if they were surgically cured.
      Data were gathered on demographic parameters, treatment given, scan
      abnormalities, prolactin levels at diagnosis and last follow up, prolactin levels
      pre- and postpregnancy as well as pre- and postmenopause. The pregnancy,
      postmenopausal and male patient groups were compared with the control group and
      each other to see if they had a higher frequency of normalization of their
      prolactin levels during follow up. Various factors were examined as possible
      variables for the normalization of prolactin, including the detection of scan
      abnormalities at diagnosis, prolactin levels at diagnosis as well as treatment
      with dopamine agonists and duration of follow up. RESULTS: Forty-five percent of
      the menopausal group, 24% of the pregnancy group and 18% of the male group
      subsequently normalized their prolactin levels during the period of the study in
      comparison with 7% of the control group. The menopausal groups had a
      significantly higher chance of normalizing their prolactin compared to the
      control group (P < 0.005), whilst the pregnancy group showed a non-significant
      trend towards normalizing their prolactin (P = 0.06). The detection of scan
      abnormalities, treatment with dopamine agonist therapy and duration of follow up
      were not associated with normalization of prolactin levels. CONCLUSION: Female
      patients with hyperprolactinaemia who pass through the menopause have a
      significant chance of normalizing their prolactin levels. Females who pass
      through pregnancy may have a higher chance of normalizing their prolactin levels.
      The menopause is an indication for reassessment of the need to continue to treat
      hyperprolactinaemia and microprolactinoma.

PMID- 11298081
TI  - Absence of mutations in the growth hormone (GH)-releasing hormone receptor gene
      in GH-secreting pituitary adenomas.
AB  - OBJECTIVE: GH-releasing hormone (GHRH) is a potent stimulator of somatotroph cell
      proliferation and GH secretion. GHRH acts via binding to a G-protein coupled
      receptor (GPCR) (GHRH-R), that activates adenylyl cyclase (AC) and increases
      growth and function of somatotroph cells. Indeed, a subset (30--40%) of
      somatotrophic adenomas contain somatic mutations of the GNAS1 gene that encodes
      the alpha subunit of the G-protein (G(s)alpha) that stimulates AC. As activating
      mutations of other GPCRs cause development of endocrine tumours, we hypothesized
      that somatic activating mutations of the GHRH-R might provide the molecular basis
      for somatotroph cell proliferation in a subset of human GH-secreting pituitary
      adenomas. DESIGN: We analysed genomic DNA isolated from 26 somatotrophinomas, 17
      of which lacked activating mutations in the GNAS1 gene. We individually amplified
      via polymerase chain reaction all 13 coding exons and the exon-intron boundaries
      of the GHRH-R gene. We used denaturing gradient gel electrophoresis to search for
      abnormalities in exons 1 through 11. Abnormally migrating bands were subjected to
      direct sequencing. Exons 12 and 13, encoding for the intracellular C-terminal
      domain, were subjected to direct sequencing. RESULTS: Mutations were not detected
      in any of the tumours, but a rare polymorphism in codon 225 corresponding to the
      third transmembrane domain (V225I) was discovered. CONCLUSIONS: GHRH-R mutations
      are absent or rare in somatotrophinomas, and other mechanisms must explain the
      somatotroph cell proliferation in the adenomas that lack activating mutations in
      the GNAS1 gene.

PMID- 11298082
TI  - The expression of thyrotrophin-releasing hormone receptor 1 messenger ribonucleic
      acid in human pituitary adenomas.
AB  - OBJECTIVE: Thyrotrophin-releasing hormone (TRH) paradoxically induces the release
      of growth hormone (GH) when injected intravenously into acromegalic patients,
      although the mechanism of this action is unknown at present. Several research
      groups have reported that the level of TRH receptor-1 (TRHR-1) mRNA expression is
      variable in pituitary adenomas, and does not correlate with the degree of
      paradoxical GH response to TRH administration in a limited number of acromegalic
      patients. We aimed to compare the expression levels of TRHR-1 mRNA among various
      types of pituitary adenoma and to clarify whether these levels correlate with the
      degree of pituitary hormone response to TRH. PATIENTS: Pituitary adenoma tissue
      was obtained by surgery from 14 patients with acromegaly, four with
      prolactinomas, nine with nonfunctioning adenomas and one with a TSH-producing
      adenoma. METHODS: The level of human TRHR-1 mRNA expression in each adenoma was
      quantified using the competitive reverse transcription polymerase chain reaction
      (RT-PCR) METHOD: For amplification of a TRHR-1 cDNA fragment, a sense primer was
      designed according to the sequence in exon 2 and an antisense primer designed
      according to the sequence located at the region in exon 3 that does not encode
      for the alternative splicing-generated short form of TRHR-1 mRNA. RESULTS: TRHR-1
      mRNA was detected in all pituitary adenomas examined and did not correlate with
      their size. The mean level of TRHR-1 mRNA expression was significantly lower in
      GH-producing adenomas than in prolactinomas and nonfunctioning adenomas (1.4 +/-
      0.4 x 10(-2) attomol/microg total RNA, 10.7 3.4 x 10(-2) attomol/microg total
      RNA, and 7.2 +/- 3.3 x 10(-2) attomol/g total RNA, respectively). The ratio of
      plasma peak GH induced by TRH administration to the basal level of plasma GH in
      the patients with acromegaly correlated positively with the level of TRHR-1 mRNA
      expression in their GH-producing adenomas (r = 0.620, P = 0.0179). The
      responsiveness of plasma PRL and gonadotrophin to TRH in the patients with
      prolactinoma and nonfunctioning pituitary adenoma did not significantly correlate
      with the levels of TRHR-1 mRNA expression in their pituitary adenomas,
      respectively. CONCLUSIONS: The findings of the present study suggest that the
      level of TRHR-1 mRNA expression varies among different types of pituitary
      adenoma. Furthermore, in acromegaly, the responsiveness of plasma GH to TRH
      administration appears to at least partially depend on the level of TRHR-1 mRNA
      expression in the GH-producing pituitary adenoma.

PMID- 11298083
TI  - Mdm2 and the p53 pathway in human pituitary adenomas.
AB  - OBJECTIVE: Studies on pituitary tumours have failed to identify mutations in the
      tumour suppressor gene p53 suggesting that the protein identified is wild type.
      p21(WAF--1) is a downstream effector of p53 which promotes growth arrest. Mdm2
      (mouse double minute) is a protein induced by wild type p53 and forms an
      autoregulatory feedback loop suppressing wild type p53 activity. The purpose of
      this study was to examine a group of pituitary tumours for expression of p53 and
      its two downstream effector proteins p21(WAF--1) and mdm2 and to compare this
      with their radiological invasive status and proliferative potential as assessed
      by Ki-67 expression. SUBJECTS AND METHODS: Sixty-nine tumours removed at
      transsphenoidal surgery were examined by immunocytochemistry using antibodies
      against p53, p21(WAF--1), mdm2 and Ki-67 (MIB-1). The invasive status of the
      tumours was determined from the preoperative CT/MRI scans. RESULTS: p53 was
      expressed in 42 of 69 (61%) pituitary adenomas but there was no relationship with
      either pituitary tumour invasive status (P = 0.71) or volume (P = 0.33). p53
      expression correlated, however, with the proliferative state of the tumours as
      assessed by the MIB-1 labelling index (P = 0.0065). Invasive tumours had a higher
      growth fraction than non-invasive ones (P = 0.027). p21(WAF--1) was expressed in
      the nuclei of 58/69 (84%) pituitary adenomas and its expression correlated with
      that of p53 (r = 0.26, P = 0.03). Mdm2 was expressed in the cytoplasm of 46/69
      (67%) tumours and this correlated with the nuclear staining for p53 (P = 0.022)
      while nuclear staining was seen in 32/69 (46%) tumours but this did not correlate
      significantly with nuclear p53 staining (P = 0.096). CONCLUSIONS: These results
      suggest that p53, p21(WAF--1) and mdm2 are all expressed in pituitary tumours
      suggesting that the p53 protein detected by immunocytochemistry is wild type.
      Expression of p53 is associated with tumours which have a higher proliferative
      status. The p53 activity is probably the result of upstream signals of local
      stresses mediated through either genetic change, cytokines, hypoxia or hormonal
      factors. Our results suggest, however, that the downstream pathway mediated
      through the activities of p21(WAF--1) and mdm2 may be dysfunctional in these
      tumours.

PMID- 11298084
TI  - Serum antibodies to human pituitary membrane antigens in patients with autoimmune
      lymphocytic hypophysitis and infundibuloneurohypophysitis.
AB  - OBJECTIVE: Serum antipituitary antibodies were investigated by the immunoblotting
      method using human anterior pituitary membrane preparation as the antigen.
      PATIENTS: Thirteen patients with autoimmune lymphocytic hypophysitis, two
      patients with infundibuloneurohypophysitis, four patients with isolated ACTH
      deficiency, 21 patients with diabetes mellitus (type 1 and type 2) and 38 healthy
      subjects were studied. METHODS: Human pituitary membrane antigens were
      electrophoresed by sodium dodecylsulphate-polyacrimide gel electrophoresis (SDS
      PAGE). The antigens were transferred to polyvinylidene difluoride membrane and
      reacted with the sera followed by incubation with biotinylated anti-human IgG
      goat serum. RESULTS: Serum antibodies to 68, 49, 43 kD human pituitary membrane
      antigens were detected in five of 13, one of 12 patients with
      infundibuloneurohypophysitis and none of four patients with isolated ACTH
      deficiency. These antibodies were not detectable when human thyroid, liver or rat
      pituitary preparations were used as the antigen. CONCLUSION: These findings
      suggest that serum antibodies to 68, 49, 43 kD human anterior pituitary antigen
      are specific but not so frequently detected in autoimmune lymphocytic
      hypophysitis.

PMID- 11298085
TI  - Screening for an AIRE-1 mutation in patients with Addison's disease, type 1
      diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED
      syndrome.
AB  - OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) is a rare systemic autoimmune disorder of monogenic and autosomal
      recessive inheritance. To date, 29 APECED causing mutations have been identified
      in the responsible gene AIRE-1, coding for a regulator of transcription. The aim
      of this study was to examine whether mutations in AIRE-1, in their heterozygous
      form, predispose to the more common isolated autoimmune endocrinopathies
      Addison's disease, type 1 diabetes mellitus, Graves' disease and Hashimoto's
      thyroiditis. DESIGN: Patients with isolated autoimmune endocrine disorders as
      well as healthy controls were analysed for two of the most common AIRE-1
      mutations, mutation R257X in exon 6 and a 13-bp deletion in exon 8. Mutations
      were detected by polymerase chain reaction based techniques. PATIENTS: In total,
      726 individuals were investigated for mutation R257X. Subjects comprised patients
      with Addison's disease, IDDM, Graves' disease and Hashimoto's thyroiditis. With
      regard to the 13 bp deletion we could screen 91 patients with Addison's disease.
      In addition, six patients with the APECED syndrome including one family were
      analysed for both mutations. RESULTS: Out of the 12 alleles in APECED patients
      six contained either mutation R257X or the 13 bp deletion, confirming that these
      mutations prevail in Europe. R257X was found in one subject with Hashimoto's
      thyroiditis in its heterozygous form. The 13 bp deletion was not detected in any
      subject with Addison's disease. CONCLUSIONS: The two studied AIRE-1 mutations are
      so rare in the general population that they can not contribute to susceptibility
      for the more common isolated autoimmune disorders.

PMID- 11298086
TI  - Influence of melatonin administration on glucose tolerance and insulin
      sensitivity of postmenopausal women.
AB  - OBJECTIVE: The effect of melatonin on human carbohydrate metabolism is not yet
      clear. We investigated whether melatonin influences glucose tolerance and insulin
      sensitivity in aged women. PATIENTS: Twenty-two postmenopausal women of whom 14
      were on hormone replacement therapy. DESIGN: After an overnight fast, at 0800
      hours on two nonconsecutive days, placebo or melatonin (1 mg) were administered
      randomly and in a double blind fashion. Forty-five minutes later, an oral glucose
      tolerance test (75 g; OGTT) was performed in 13 women. In another nine women
      insulin-dependent (Si) and -independent (Sg) glucose utilization was tested by a
      frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: Areas
      under the response curve to OGTT (AUC) for glucose (1420 +/- 59 vs. 1250 +/- 55
      mmol x min/l; P < 0.01), and C-peptide (42,0980 +/- 45,320 vs. 33,528 +/- 15,779
      pmol x min/l; P < 0.02) were higher following melatonin than placebo, while Si
      values were lower (2.6 +/- 0.28 units vs. 3.49 +/- 0.4 units; P < 0.03). Si
      modifications induced by melatonin were inversely related to Si values of the
      placebo day (r(2) = 0.538; P < 0.025). CONCLUSIONS: The present results indicate
      that in aged women administration of 1 mg of melatonin reduces glucose tolerance
      and insulin sensitivity. The present data may have both physiological and
      clinical implications.

PMID- 11298087
TI  - T lymphopaenia in relation to body mass index and TNF-alpha in human obesity:
      adequate weight reduction can be corrective.
AB  - OBJECTIVE: Although individuals with obesity are susceptible to infection, the
      underlying causes have not been fully identified. To investigate whether obesity
      affects immunity, we studied subjects with isolated obesity. DESIGN AND SUBJECTS:
      Thirty-four obese persons from our outpatient obesity clinic and 50 nonobese
      healthy control subjects were studied. The effects of weight reduction were
      evaluated in obese subjects on a very-low-energy diet. We examined blastogenic
      response, lymphocyte subsets, circulatory TNF-alpha, soluble TNF-alpha receptor
      1, soluble TNF-alpha receptor 2, and in vitro TNF-alpha production in obesity.
      MEASUREMENTS: Lymphocyte subsets were analysed with flowcytometry. TNF-alpha and
      soluble TNF receptors levels were assayed using commercially available enzyme
      linked immunosorbent assay kits. RESULTS: Blastogenic responses to
      phytohemagglutinin or concanavalin A of T cells, CD3(+), CD4(+), CD8(+),
      CD4(+)CD45RO(+), and TCR alpha beta T cells were significantly diminished in
      obese subjects. Strong negative correlations were observed between TCR alpha beta
      and body weight and BMI in obese subjects. Circulatory levels of TNF-alpha,
      soluble TNF-alpha receptors, and in vitro TNF-alpha production were significantly
      increased compared to nonobese subjects. In obese subjects, there were
      significant positive correlations between serum levels of TNF-alpha and waist-hip
      ratio, serum levels of soluble TNF-alpha receptor 1 and body weight, soluble TNF
      alpha receptor 2 and BMI, and soluble TNF-alpha receptor 2 and waist-hip ratio.
      The T cell responses and previously reduced non-CD8 T cell subsets were increased
      significantly following weight reduction. CONCLUSIONS: Our results suggest that
      subsets of T cell populations and their function may be reduced in human obesity,
      and that this may be related, at least in part, to the elevated TNF-alpha
      production. Furthermore, this T cell dysfunction can be recovered by adequate
      weight reduction.

PMID- 11298088
TI  - A luminescent bioassay for thyroid blocking antibodies.
AB  - OBJECTIVE: Thyroid blocking antibodies (TBAb) have a role in the development of
      hypothyroidism and in the neonate are responsible for transient hypothyroidism.
      Specific measurement of TBAb requires a bioassay, but current methods are lengthy
      and cumbersome. We describe a rapid luciferase-based method for the detection of
      TBAb using the lulu* cell line which is suitable for the provision of a clinical
      service PATIENTS AND MEASUREMENTS: Chinese hamster ovary (CHO) cells were
      transfected with human TSH-R together with G418 resistance and a cAMP responsive
      luciferase construct. Stable pools of transfected cells were selected and clones
      identified by limiting dilution. Clone lulu* gave the best response to
      stimulation by TSH and was used to develop a bioassay for TBAb. The luminescent
      bioassay conditions have been optimized and validated using 12 serum samples from
      patients found to be TBAb positive in a bioassay using an established method
      quantifying cAMP by radioimmunoassay (RIA). The effect of thyroid stimulating
      antibodies (TSAb) on the calculation of Inhibition Index (InI) using two
      previously described formulae have been investigated and we have used serum
      containing both TSAb and TBAb to investigate detection of TBAb in samples
      containing more than one type of activity. RESULTS: Lulu* displays a dose
      dependent increase in luciferase expression in response to stimulation with
      bovine (b) TSH which is more effective in serum free medium than in salt free
      buffer. TSH stimulated luciferase expression can be inhibited by TBAb in either
      serum or an immunoglobulin preparation. Using optimized assay conditions,
      challenging 10% serum against 1 U/l bTSH in culture medium, we have tested 31
      euthyroid sera to determine a reference range: InI values >23% were considered
      positive. Twelve samples previously shown to contain TBAb by an established
      method quantifying cAMP by RIA were positive by the luciferase-based assay. Of
      control sera, 20/20 systemic lupus erythematosus, 13/14 rheumatoid arthritis,
      12/12 multinodular goitre were negative. We demonstrated that if more complex
      formulae are used to calculate InI, false positive TBAb results can be obtained
      in samples containing only TSAb. Finally, when sera contain both TSAb and TBAb,
      the net activity of stimulating and blocking antibodies is detected in the
      bioassay. Where TSAb are also present, analysis of serum may be required at
      several dilutions to detect TBAb. CONCLUSIONS: We describe the production of a
      new cell line, lulu*, and its use to develop a luminescent bioassay for TBAb
      suitable for clinical use. Comparing two established methods of calculating TBAb,
      we found that they do not give identical results. In light of this, the high
      prevalence reported for TBAb in some studies has to be considered with caution.

PMID- 11298089
TI  - Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal
      low birth weight.
AB  - OBJECTIVE: Hyperthyroidism in pregnancy occurs with a prevalence of 0.05--0.2%
      and has been shown to affect neonatal outcomes. Fetal weight increases markedly
      during the third trimester of pregnancy. This retrospective study was performed
      to examine the effect of maternal hyperthyroidism during late pregnancy on
      neonatal birth weight (NBW). DESIGN: Medical and obstetric records of 293
      pregnant women with present and past history of hyperthyroidism were
      retrospectively reviewed. PATIENTS: There were 188 records of 181 patients with
      adequate data for inclusion in the analysis. The patients were divided into two
      groups according to the maternal thyroid function during the third trimester of
      pregnancy: hyperthyroidism (HT; 35 cases) and euthyroidism (ET; 153 cases).
      MEASUREMENTS: Maternal thyroid function tests were periodically evaluated before
      and during the third trimester of pregnancy. Neonatal thyroid function tests and
      birth weight of the newborn infants were also assessed. RESULTS: There was no
      significant difference of maternal age between HT and ET groups mean +/- SD (27.6
      +/- 5.5 vs. 29.2 +/- 5.4 years). The NBW of the HT group was not significantly
      different from that of the ET group (2880 +/- 590 vs. 3019 +/- 426 g). However,
      the prevalence of infants with low birth weight (LBW) defined as NBW of lower
      than 2500 g in HT group was 22.9% which was significantly higher than the 9.8% in
      the ET group (P = 0.039, OR = 2.7, 95%CI = 1.1--7.1) and 9.7% of infants born to
      healthy mothers at Siriraj Hospital (control group) between 1991 and 1995 (P =
      0.01, OR = 2.7, 95%CI = 1.3--6.1). The 90% CI for the true difference between the
      prevalence of LBW infants born to ET and HT mothers was 0.7--25.4. There was no
      significant difference in the prevalence of LBW infants in ET and control groups.
      Multiple logistic regression analyses showed that maternal hyperthyroidism during
      the third trimester of pregnancy was an independent factor associated with
      increased prevalence of LBW infants (P = 0.037, OR = 4.1, 95%CI = 1.1--15.0).
      CONCLUSIONS: Maternal hyperthyroidism during the third trimester of pregnancy
      independently increases the risk of low birth weight by 4.1-fold. Appropriate
      management of hyperthyroidism throughout pregnancy is essential in the prevention
      of this undesirable neonatal outcome.

PMID- 11298090
TI  - Congenital thyrotoxicosis in premature infants.
AB  - OBJECTIVES: Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but
      congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies
      independent of maternal disease status. Antenatal prediction of affected infants
      is imprecise; however, maternal history, coupled with a high maternal serum TSH
      receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome.
      Mortality is reported to be as high as 25% in affected infants and would
      therefore be expected to be higher in premature infants. This study illustrates
      that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth
      retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence
      of antenatal risk assessment and management of thyrotoxicosis in this setting is
      complex. DESIGN AND PATIENTS: The records of premature neonates born at the three
      main maternity units in Brisbane, between January 1996 and July 1998 diagnosed
      with congenital thyrotoxicosis were reviewed. Data were recorded on gestational
      age, birth weight (B Wt), maternal thyroid history and current status, and
      neonatal course. Thyroid function and TBII status was assessed using standard
      biochemical assays. RESULTS: Seven neonates from five pregnancies were identified
      (four female, three male). Mean gestational age was 30 week (25--36 week) and
      median B Wt was 1.96 kg (0.50--2.62 kg). Only one mother received formal
      antenatal counselling by a paediatric endocrine service and had a TBII (54%)
      measured prior to delivery. Three of five mothers had elevated TBII measured
      after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was
      not performed. All mothers were biochemically euthyroid at delivery. Mean age at
      diagnosis was 9 days (1--16 days) and mean age at commencement of treatment was
      12 days (7--26 days). Two infants received propylthiouracil and five received a
      combination of carbimazole and propranolol. Four became biochemically
      hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD),
      and one required ongoing T4 supple-mentation. Only one infant required treatment
      for cardiac failure and there were no deaths in this cohort. CONCLUSIONS: This is
      a large series of extremely small and premature infants with neonatal thyro
      toxicosis. Presentation was nonspecific. The diagnosis was delayed because of low
      birth weight, prematurity, multiple birth and/or an unrecognized maternal history
      of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in
      these extreme low birth weight infants yet no infant died and significant
      morbidity was confined to high output cardiac failure in one infant. With
      antenatal recognition of past or active Graves' disease, assessment of maternal
      TSH receptor binding immunoglobulin index prior to delivery and postnatal
      monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of
      affected infants may have further reduced neonatal morbidity.

PMID- 11298091
TI  - The biochemical and clinical course of postpartum thyroid dysfunction: the
      treatment decision.
AB  - OBJECTIVE: To follow the clinical and biochemical course of a cohort of women who
      had postpartum thyroid dysfunction (PPTD) at 6 months postpartum and to examine
      the treatment practices of general practitioners and endocrinologists in the
      setting of PPTD. DESIGN: Prospective longitudinal study. SETTING: Metropolitan,
      Perth, Australia. PARTICIPANTS: Eighty-six Caucasian women who were identified to
      have PPTD at 6 months postpartum in a cross-sectional study of 748 women. MAIN
      OUTCOME MEASURES: Characteristics of the clinical and biochemical course of PPTD
      and documentation of the treatment practices and factors influencing treatment of
      PPTD by general practitioners and endocrinologists. RESULTS: Sixteen of 86 women
      (19%) were receiving treatment at 9 months postpartum and by 30 months postpartum
      27% of women had received treatment for PPTD. Fifty-one percent of those not
      treated were biochemically euthyroid at 9 months, although, for those with
      hypothyroid biochemistry at 6 months, the median TSH at 18 months was at the
      upper limit of the reference range. Thyroid peroxidase antibody titre fell over
      the 2 years of follow-up. There was no significant change in clinical parameters
      over the study. Forty-nine percent of endocrinologists and 73% of general
      practitioners reported that they required clinical signs or symptoms before
      initiating treatment for hypothyroid PPTD. CONCLUSIONS: In a cohort of women with
      postpartum thyroid dysfunction, a quarter received treatment. Elevated TSH in
      untreated women does not completely return to the normal median. The role of
      clinical assessment in treatment decision-making differs between primary care
      physicians and endocrinologists. A case is made for the early Institution of
      permanent thyroxine replacement in women with postpartum thyroid dysfunction,
      elevated TSH and positive thyroid antibodies.

PMID- 11298092
TI  - Efficacy of single daily dosage of methimazole vs. propylthiouracil in the
      induction of euthyroidism.
AB  - OBJECTIVE: Previous studies of the treatment of hyperthyroidism with a single
      daily dose of antithyroid drugs have demonstrated a favourable result with
      methimazole (MMI). However, the efficacy of a single daily dose of
      propylthiouracil (PTU) was inconsistent. The present prospective randomized study
      was conducted to compare the efficacy of a single daily dose of MMI and PTU in
      the induction of euthyroidism in patients with Graves' disease. SUBJECTS: Seventy
      one patients with newly diagnosed Graves' disease were studied. METHODS AND
      MEASUREMENTS: Patients were randomized to two groups to receive once daily dose
      of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was
      determined biochemically by serum total T3, total T4 and TSH levels at baseline
      and at 4, 8 and 12 weeks during the study period. RESULTS: There was no
      significant difference in baseline characteristics. Serum total T3 levels of the
      MMI group were significantly lower than those of the PTU group after four weeks
      of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the
      end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes
      in serum total T4 levels occurred in the same direction as serum total T3 levels
      but a significant difference was observed only after eight weeks of the treatment
      (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end
      of the study, more patients in the MMI group had both serum total T3 and T4
      levels less than the upper limit of the normal range compared to the PTU group
      (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the
      MMI group but not in the PTU group. CONCLUSIONS: During 12-weeks' treatment of
      Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more
      effective in the induction of euthyroidism than a single daily dose of 150 mg of
      PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more
      rapidly but also induced euthyroidism four times more effectively than did the
      once daily regimen of PTU. In the doses used in this study, MMI is preferable to
      PTU when a once-daily regimen of antithyroid drug is considered for the treatment
      of hyperthyroidism.

PMID- 11298093
TI  - Interpretation and validity of changes in scores on the Graves' ophthalmopathy
      quality of life questionnaire (GO-QOL) after different treatments.
AB  - OBJECTIVE: The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) is
      the first instrument available to measure health-related quality of life (HRQL)
      of patients with Graves' ophthalmopathy. The main objective of this study was to
      define a minimal clinically important difference (MCID) in score on the GO-QOL
      that can be considered an important improvement in HRQL by examining changes in
      GO-QOL scores in patients who subjectively report improvement from their
      treatment. A secondary objective was to test the longitudinal validity of the GO
      QOL, using prespecified hypotheses about expected treatment effects. DESIGN: A
      prospective cohort study. PATIENTS: We included 164 patients who were scheduled
      for radiotherapy (23), orbital decompression (10 for sight loss, 38 for
      exophthalmos), eye muscle surgery (31), eyelid lengthening (43) or blepharoplasty
      (19). MEASUREMENTS: Patients completed the GO-QOL and three general HRQL
      questionnaires, before and three or six months after treatment, depending on the
      performed procedure. Clinical characteristics were collected from the medical
      records. Mean changes in GO-QOL scores and effect sizes were calculated after
      different treatments, and in subgroups of responders and nonresponders according
      to clinical characteristics and according to the patients themselves. RESULTS: A
      clinical response to treatment was associated with a change in GO-QOL scores of
      approximately 10--20 points after major treatments (radiotherapy or
      decompression), and with a change of approximately 3--10 points after minor
      surgery (eye muscle surgery, eyelid lengthening, blepharoplasty). Changes in GO
      QOL scores of about 6--10 points were considered important improvements by the
      patients themselves. The direction and amount of change in GO-QOL scores after
      different treatments were in accordance with our prespecified hypotheses about
      treatment effects. Effect sizes in the GO-QOL subscales were generally higher
      than effect sizes of the general HRQL subscales, supporting the longitudinal
      validity of the GO-QOL. CONCLUSIONS: As a general guideline, one could consider a
      mean change of at least 6 points on one or both subscales an important change in
      daily functioning for patients. For more invasive therapies, a change of at least
      10 points is recommended as a minimal clinically important difference.

PMID- 11298094
TI  - Long-term mifepristone (RU486) therapy resulting in massive benign endometrial
      hyperplasia.
AB  - Mifepristone (RU486) is a potent antiprogestagen, and at high doses it also acts
      as an antiglucocorticoid drug. Mifepristone, administered as a single 600 mg
      dose, is commonly employed to induce medical abortion in conjunction with
      prostaglandins. The long-term safety profile of mifepristone, especially at high
      doses, is less well-established. Long-term mifepristone is considered efficacious
      in treating uterine myomas, endometriosis (25--100 mg/day), and possibly in
      inoperable meningiomas (200 mg/day), as well as inoperable Cushing's syndrome.
      Many animal studies document an antiproliferative effect (antioestrogenic), as do
      some reports in humans. However, there are also data to suggest that, as an
      antiprogestagen, mifepristone may promote an unopposed oestrogen milieu, and thus
      have a proliferative effect upon the endometrium. We hereby describe the first
      reported case of an adolescent female with Cushingoid features and morbid
      osteoporosis who was treated with mifepristone for its antiglucocorticoid effect
      (400 mg/day) in an attempt to prevent further bone loss. The patient's striae,
      weight gain, and buffalo hump markedly improved, and further bone loss was
      halted. However, with each of the two 6-month courses of mifepristone (9 months
      apart) she developed massive simple endometrial hyperplasia and a markedly
      enlarged uterus. This reversed to normal after cessation of mifepristone
      treatment. In conclusion, High doses of the antiprogestagen mifepristone over a
      prolonged period of time may promote an unopposed oestrogen milieu leading to
      endometrial hyperplasia. Therefore, interval pelvic imaging in women who receive
      long-term mifepristone may be prudent.

PMID- 11298095
TI  - Interleukin-6 (IL-6) producing phaeochromocytoma: direct IL-6 suppression by non
      steroidal anti-inflammatory drugs.
AB  - A 35-year-old Japanese woman presented with a phaeochromocytoma and demonstrated
      marked inflammatory reactions and pyrexia as a result of excessive production of
      interleukin-6 (IL-6) by the tumour. Serum IL-6 level was 262 ng/l (normal; < 4.0
      ng/l). Fever and inflammatory markers were largely overcome by the administration
      of the nonsteroidal anti-inflammatory drug, naproxen, and all symptoms
      disappeared soon after the tumour was excised. Immunohistochemical study revealed
      positive staining using an antihuman IL-6 antibody and Northern analysis showed
      increased IL-6 mRNA levels in the tumour. Cultured tumour cells showed IL-6
      protein synthesis, and nonsteroidal anti-inflammatory drugs such as naproxen and
      indomethacin directly inhibited IL-6 release. These results indicate that the
      effects of naproxen in vivo were due, at least in part, to direct suppression of
      IL-6 secretion from the tumour.

PMID- 11298096
TI  - Increased prevalence of thyroid autoimmunity in patients successfully treated for
      Cushing's disease.

PMID- 11298099
TI  - Serum TSH concentration and the probability of developing hypothyroidism.

PMID- 11298098
TI  - A case of congenital generalized lipodystrophy: metabolic effects of four dietary
      regimens. Lack of association of CGL with polymorphism in the lamin A/C Gene.

PMID- 11298100
TI  - A review of high-dose intravenous immunoglobulin (hdIVIg) in the treatment of the
      autoimmune blistering disorders.
AB  - High-dose intravenous immunoglobulin (hdIVIg) is being used increasingly for
      dermatological indications. Its mode of action is via a number of proposed
      mechanisms and it is not associated with the many side-effects of steroids and
      other immunosuppressive agents. The evidence for using hdIVIg in the treatment of
      autoimmune bullous disorders is based on uncontrolled trials and case reports.
      However, there are now 62 reported patients and this review aims to make a
      critical assessment of the current data. This has been obtained from a Medline
      search of the English literature from 1966 to 2000 for pemphigus vulgaris,
      pemphigus foliaceus, bullous pemphigoid, pemphigoid gestationis, cicatricial
      pemphigoid, epidermolysis bullosa acquisita and linear IgA disease. Taken
      together hdIVIg was effective in 81% of the patients with blistering disease.
      Patients appear to be more likely to respond when hdIVIg is used as adjunctive
      therapy (91% response rate) than as monotherapy (56% response rate). hdIVIg may
      offer a safe potential therapeutic avenue for resistant cases of the autoimmune
      bullous disorders but should be further assessed using double-blind placebo
      controlled trials.

PMID- 11298101
TI  - Contact urticaria.
AB  - Contact urticaria has been reported following skin contact with a multitude of
      substances ranging from simple chemicals to macromolecules. Its prevalence
      amongst the general population is unknown, but it may be a relatively common and
      under-recognized phenomenon. Non-immunological (irritant) causes typically elicit
      mild localized reactions, which clear within hours. Such agents can be found
      widely in food, cosmetics and medicaments. The lower diagnostic end-point for
      nonimmunological contact urticaria has been the subject of debate, which makes
      interpretation of the literature difficult. Immunological (allergic) contact
      urticaria is due to immediate-type hypersensitivity, and occurs most commonly in
      atopic individuals. It is mediated primarily by histamine, and may be associated
      with systemic, and potentially life-threatening symptoms. Natural rubber latex is
      one of the most important causes today, and the recent 'epidemic' of latex
      protein allergy has helped draw attention to this subject. Immunological contact
      urticaria to animal or vegetable matter may occasionally affect those who handle
      food, and other occupations such as agricultural and veterinary workers. This may
      be associated with development of a protein contact dermatitis. The diagnosis of
      immunological contact urticaria can often be confirmed by simple investigations
      such as skin prick testing or measurement of specific IgE.

PMID- 11298102
TI  - Sunburn in children -- the Aberdeen experience.
AB  - Sun exposure in children is known to be a risk factor for the development of
      malignant melanoma in later life. The incidence of melanoma in the UK is
      increasing more rapidly than that of most other malignant tumours and there is
      now increasing awareness in adults of the necessity to protect against over
      exposure and sunburn. However sun protection of children in the UK is generally
      less than optimum and it would appear that parents and children are unaware of
      the long-term risks of over-exposure to the sun. This study demonstrates
      significant morbidity from sunburn even in the temperate climes of the north-east
      of Scotland. It is suggested that strategies to reduce melanoma incidence should
      begin at an early age with preventative education for children, their parents,
      carers and teachers.

PMID- 11298103
TI  - Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic
      myeloid leukaemia.
AB  - Hydroxyurea is an antimetabolite agent used in the treatment of
      myeloproliferative disorders and sickle cell anaemia. Although hydroxyurea is
      relatively well tolerated, adverse effects often involve skin and mucous membrane
      during long-term therapy. A group of 510 patients affected by chronic myeloid
      leukaemia from 1977 to 1998 has been considered. Only 158 patients were treated
      with hydroxyurea and fulfilled inclusion/exclusion criteria of this study. A
      spectrum of severe cutaneous and mucosal changes (inflammatory and neoplastic)
      was seen in about 13% of patients (21 patients out of 158) and was studied in
      detail. Cutaneous and mucosal atrophy were observed in all 21 patients. Skin
      atrophy was often characterized by numerous telangiectases, especially on legs
      and on sun-exposed sites (16/21). Cutaneous, mucosal and nail hyperpigmentation
      was evident, albeit with variable extent, in 10 of the 21 patients. Severe
      stomatitis and glossitis with flattening of papillae were another common finding.
      Five patients, who received a particularly long treatment with hydroxyurea,
      developed squamous-cell neoplasms on sun-exposed sites (both squamous-cell
      carcinomas and keratoacanthomas). Acral changes were characteristic and constant,
      including acral erythema (21/21), dermatomyositis-like changes on the dorsa of
      hands (7/21), ulcers localized on acral areas of legs, on genitalia and oral
      mucosae (20/21). The frequency and the variety of these muco-cutaneous changes
      are reported and the mechanisms by which hydroxyurea may induce this muco
      cutaneous syndrome-like group of changes, are proposed.

PMID- 11298104
TI  - A pilot study of treatment of herpes labialis with 1072 nm narrow waveband light.
AB  - A randomized prospective double-blind study was performed to compare the efficacy
      of a single 5 min 1072 nm narrow waveband light application against topical
      aciclovir applied five times daily in the treatment of herpes labialis. Treatment
      was initiated within 36 h of the onset of symptoms and the end point was defined
      as the day that the crust was discarded leaving an uninterrupted underlying skin
      at the site of the cold sore. The results demonstrated that a single 5 min light
      treatment significantly reduced cold sore healing time by 4 days; 1072 nm light
      healed cold sores in 4.3 +/- 1.8 days (mean +/- SD) as compared with aciclovir
      applied five times daily, 8.5 +/- 3.0 days (P < 0.0001).

PMID- 11298105
TI  - Peroxisomal proliferator-activated ligand therapy for HIV lipodystrophy.
AB  - Lipodystrophies associated with HIV disease have been reported in recent years
      and have included a general redistribution of fat with more central fat and
      increased dorsocervical fat. These lipodystrophies are commonly associated with
      hyperlipidemia and in some cases with insulin resistant diabetes. Although a
      similar redistribution of fat is seen in hypercortisolism, in general, serum and
      urinary cortisol levels are normal in these HIV-positive patients. However
      cortisol/dehydroepaindrosterone (DHEA) ratios are increased in HIV disease and
      may result in a relative hypercortisolism. Seven HIV-positive male patients on
      multidrug antiviral therapy including HIV protease inhibitors had developed
      increased central and dorsocervical fat over 1 year. All patients had increased
      serum lipids and three had insulin resistant diabetes. Four patients were treated
      initially with DHEA 100-200 mg/day, with addition of a cyclo-oxygenase (COX)
      inhibitor (indomethacin 100 mg/day) and three others were treated from the onset
      with a combination of DHEA 200 mg/day and a COX inhibitor (indomethacin 100
      mg/day or naprosyn 1000 mg/day). All patients reported moderation or
      normalization of their serum lipids and some moderation of blood sugars while on
      DHEA alone. More marked improvement in blood sugar and noticeable decreases in
      the dorsocervical fat; however, occurred only with addition a COX inhibitor. Both
      DHEA and COX inhibitors have a number of mechanisms of action; among these is
      their role as a peroxisome proliferator-activator receptor ligand. Dysregulation
      of peroxisome function is associated with the spectrum of biochemical changes
      seen within these HIV associated lipodystrophies. Use of HIV protease inhibitors
      is reported in the majority of patients with these lipodystrophies, and protease
      inhibitors may accentuate the underlying peroxisome dysregulation.
      Supplementation with DHEA and a COX inhibitor may improve peroxisomal function.

PMID- 11298106
TI  - Neutrophilic eccrine hidradenitis in two neutropaenic patients.
AB  - We describe two patients, who presented with erythematous facial plaques, in
      keeping with neutrophilic eccrine hidradenitis, during chemotherapy for acute
      myeloid leukaemia. Both patients were neutropaenic and febrile. Histology showed
      a dermal neutrophilic infiltrate around the eccrine glands with gland
      destruction. The importance of recognizing this disorder is to prevent the
      inappropriate use of antibiotics as it is self limiting.

PMID- 11298108
TI  - Cytomegalovirus-associated gastric ulcer in an immunosuppressed patient with
      pemphigus vulgaris.
AB  - A 79-year-old female with pemphigus vulgaris developed a cytomegalovirus (CMV)
      associated gastric ulcer whilst on standard immunosupression with azathioprine
      and prednisolone. Following treatment with ganciclovir and ranitidine the ulcer
      healed. CMV infection frequently involves the gastrointestinal tract of
      immunocompromised patients causing inflammation, ulceration and haemorrhage.
      Although it has also been described in patients treated with immunosuppressive
      therapy for malignancy and other autoimmune disease, we are not aware of previous
      reports in patients treated for autoimmune bullous disease.

PMID- 11298107
TI  - Systemic B-cell lymphoma presenting as an isolated lesion on the ear.
AB  - We report a case of systemic B-cell lymphoma that presented as an isolated
      cutaneous lesion on the ear, mimicking a primary cutaneous B-cell lymphoma.
      Although there was no clinical evidence of systemic disease, bone marrow
      involvement was found on further investigation and subsequent immunoglobulin gene
      analysis revealed an identical clone in the skin lesion and bone marrow aspirate.
      Evidence of a t(14 : 18) translocation was not identified. This case is unusual
      for several reasons. First, involvement of the pinna as a presenting feature of
      systemic lymphoma has not been reported previously. Second, the cutaneous lesion
      had been present for 3 years prior to diagnosis and there has been no clinical
      progression of systemic lymphoma during 2 years of follow-up. Third, the lymphoma
      does not correspond exactly to any of the entities in the REAL classification of
      systemic B-cell lymphoma. This case underlines the indolent nature of some
      systemic B-cell lymphomas and the need to investigate thoroughly patients with
      disease apparently confined to the skin.

PMID- 11298109
TI  - Malignant T-cell lymphoma mimicking lepromatous leprosy.
AB  - We describe a 16-year-old Filipino boy who presented with skin lesions highly
      suggestive of lepromatous leprosy, but further assessment established a diagnosis
      of malignant T-cell lymphoma. This case emphasizes the extensive differential
      diagnosis of leprosy, as well as the importance of obtaining skin biopsies for
      diagnostic confirmation.

PMID- 11298110
TI  - Tissue-engineered dermal skin grafting in the treatment of ulcerated necrobiosis
      lipoidica.
AB  - Necrobiosis lipoidica is a well recognized but comparatively rare cutaneous
      complication of diabetes mellitus. The aetiology is probably multifactorial with
      microangiopathy, immune complex formation, abnormal collagen synthesis and
      breakdown, and altered haemostasis all thought to play a part. Necrobiosis
      lipoidica often proves very resistant to treatment. We report a case of a 44-year
      old woman with ulcerated necrobiosis lipoidica that healed following grafting
      with a tissue-engineered living dermal tissue.

PMID- 11298111
TI  - Eosinophilic pustular folliculitis (Ofuji's disease): indomethacin as a first
      choice of treatment.
AB  - Eosinophilic pustular folliculitis (EPF) is characterized by erythematous patches
      of large follicular papules and pustules involving mainly the face. Although
      various treatments have been attempted for EPF, including systemic and topical
      steroid, diaphenylsulphone, colchicine, minocycline as well as UVB phototherapy,
      there is no consensus on the first choice of treatment. We report a typical case
      and summarize 25 patients with EPF treated in our hospital between 1978 and 1998.
      Indomethacin was most frequently used (12/25) and showed clinical improvement in
      the majority of the cases (11/12). The effect of indomethacin was usually
      observed within 1--2 weeks after initiation of treatment. Decrease of peripheral
      blood eosinophils accompanied the clinical improvement. Thus, indomethacin should
      be considered as a first choice of treatment for EPF.

PMID- 11298112
TI  - Hypertrichosis lanuginosa acquisita preceding extraskeletal Ewing's sarcoma.
AB  - A 62-year-old woman with acquired hypertrichosis lanuginosa as a paraneoplastic
      presenting sign of an extraskeletal Ewing's sarcoma is described. Despite initial
      comprehensive screening to rule out an associated malignancy, a definitive
      diagnosis of sarcoma was established only 1 year after the onset of the cutaneous
      symptoms. To the best of our knowledge, this is the first report of
      hypertrichosis lanuginosa acquisita associated with a soft tissue sarcoma. Our
      observation expands the spectrum of malignancies associated with this uncommon
      paraneoplastic disorder.

PMID- 11298113
TI  - Molecular genetics of cutaneous lupus erythematosus.
AB  - The cutaneous forms of lupus erythematosus (LE) are true complex traits,
      susceptibility to which is determined by multiple factors. Good evidence exists
      for both genetic and environmental components to this complexity. Several
      different experimental techniques have found the strongest genetic associations
      with cutaneous LE to include sequence polymorphisms of genes encoding HLA, TNF
      alpha and complement molecules, particularly in anti-Ro-positive patients.
      Abnormal expression of multiple other cytokines, adhesion molecules and cellular
      proteins (such as Ro and La) points towards a range of candidate genes that are
      currently being examined in cutaneous LE. Combinations of specific polymorphisms
      of genes encoding these immunoregulatory molecules may determine individual
      susceptibility to LE.

PMID- 11298114
TI  - Immunohistochemical analysis of human milk fat globulin expression in
      extramammary Paget's disease.
AB  - Primary extramammary Paget's disease is thought to be an intraepidermal carcinoma
      indicating apocrine secretory differentiation. In addition to expression in
      breast tissue, human milk fat globulin (HMFG) is expressed in the normal apocrine
      glands and tumours with apocrine differentiation. In this study HMFG expression
      in extramammary Paget's disease was analysed immunohistochemically in 18 cases of
      primary extramammary Paget's disease and two cases of secondary extramammary
      Paget's disease. The proportion and staining pattern of positive tumour cells
      with the anti-HMFG antibody was variable in each case. Cytoplasmic staining was
      observed frequently in dermal invasion and metastasis of Paget cells. The
      variabilities were thought to be due to modulation of the cellular localization
      of the cell surface component, HMFG, according to changes in cellular
      differentiation or malignant potency.

PMID- 11298115
TI  - Murine auricular transepidermal water loss -- a novel approach for evaluating
      irritant skin reaction in mice.
AB  - The standard method for evaluating contact allergy in mice is the ear swelling
      technique. However, in experimental irritant contact dermatitis, the epidermal
      barrier disruption, that represents a predominant effect of irritants, cannot be
      assayed by this METHOD: An appropriate method to evaluate barrier disruption is
      the measurement of transepidermal water loss (TEWL) but to date this has so far
      been possible only on the trunk of hairless or shaved mice. We therefore
      developed a new technique to measure the TEWL of mice ears (murine auricular
      TEWL: MATEWL). After patch testing with irritants and allergens, respectively, we
      found that the ear swelling method is most suitable for evaluating allergic skin
      reactions, whereas MATEWL is most appropriate for evaluating irritant skin
      reactions.

PMID- 11298116
TI  - Gene expression profile in a case of primary cutaneous CD30-negative large T-cell
      lymphoma with a blastic phenotype.
AB  - A 65-year-old Japanese woman presented with disseminated erythematous patches,
      plaques, and nodules on the trunk and limbs. Histological examination showed
      diffuse and dense infiltrates located in the dermis and subcutis, composed of
      large pleomorphic T lymphocytes. Immunohistochemically, neoplastic cells were
      positive for blastic T-cell markers, but negative for CD30 (Ki-1) antigen. Based
      on the clinicopathological findings, a diagnosis of primary cutaneous large T
      cell lymphoma was made. Despite systemic chemotherapy, the patient died 7 months
      after diagnosis. Gene expression profiling using complementary DNA microarrays
      indicated significantly increased expression of an apoptosis-inhibitory protein
      and certain cyokines and cytokine receptors (e.g. MCP-1, MCP-2, IP-10, and IL-2R
      gamma) in the tumour-indurated skin. Comprehensive gene expression patterning in
      additional cases may provide useful information regarding the biological and
      clinical behaviour of aggressive cutaneous lymphomas such as CD30-negative large
      T-cell lymphoma.

PMID- 11298117
TI  - DNA based molecular analysis in the rapid diagnosis of Herlitz junctional
      epidermolysis bullosa.
AB  - The junctional form of epidermolysis bullosa (JEB) is an inherited blistering
      disease in which blisters occur at the level of the lamina lucida in the
      cutaneous basement membrane zone. Specific mutations have been detected in the
      genes encoding different components of the hemidesmosomal-anchoring filament
      complex. In the recessively inherited lethal (Herlitz) type of JEB (H-JEB),
      typically nonsense mutations or insertions or deletions are present on both
      alleles of any of the three genes encoding the polypeptide subunits of the
      anchoring filament protein, laminin 5. In this study, we searched for mutations
      in a proband who presented at birth with severe and extensive blistering. We
      detected a novel 1 bp deletion and a previously reported hotspot mutation (R635X)
      in the LAMB3 gene. This mutation combination established the diagnosis of H-JEB
      in this case, in which attempted diagnosis by skin biopsy had failed. The
      molecular analysis was performed shortly after birth while the patient was
      admitted to the intensive care unit, and the definitive molecular diagnosis
      allowed the parents and physicians to devise management plans.

PMID- 11298118
TI  - Red fingers syndrome: acrosyndrome related to vascular growth endothelial factor?

PMID- 11298119
TI  - Thiols decrease cytokine levels and down-regulate the expression of CD30 on human
      allergen-specific T helper (Th) 0 and Th2 cells.
AB  - The thiol antioxidant N-acetyl- L-cysteine (NAC), known as a precursor of
      glutathione (GSH), is used in AIDS treatment trials, as a chemoprotectant in
      cancer chemotherapy and in treatment of chronic bronchitis. In vitro, GSH and NAC
      are known to enhance T cell proliferation, production of IL-2 and up-regulation
      of the IL-2 receptor. The 120-kD CD30 surface antigen belongs to the tumour
      necrosis factor (TNF) receptor superfamily. It is expressed by activated T helper
      (Th) cells and its expression is sustained in Th2 cells. We have analysed the
      effect of GSH and NAC on the cytokine profile and CD30 expression on human
      allergen-specific T cell clones (TCC). TCC were stimulated with anti-CD3
      antibodies in the presence of different concentrations of GSH and NAC. Both
      thiols caused a dose dependent down-regulation of IL-4, IL-5 and IFN-gamma levels
      in Th0 and Th2 clones, with the most pronounced decrease of IL-4. Furthermore,
      they down-regulated the surface expression of CD30, and the levels of soluble
      CD30 (sCD30) in the culture supernatants were decreased. In contrast, the surface
      expression of CD28 or CD40 ligand (CD40L) was not significantly changed after
      treatment with 20 m M NAC. These results indicate that GSH and NAC favour a Th1
      response by a preferential down-regulation of IL-4. In addition, the expression
      of CD30 was down regulated by GSH and NAC, suggesting that CD30 expression is
      dependent on IL-4, or modified by NAC. In the likely event that CD30 and its
      soluble counterpart prove to contribute to the pathogenesis in Th2 related
      diseases such as allergy, NAC may be considered as a future therapeutic agent in
      the treatment of these diseases.

PMID- 11298120
TI  - Age-related autoantibody production in a nonhuman primate model.
AB  - Autoantibody production increases with ageing. However, the pathological
      significance of this increase as well as the corresponding underlying mechanisms
      are poorly understood. To further our understanding of the role that ageing plays
      in the development of autoantibody responses, we used a novel nonhuman primate
      model consisting of healthy baboons of ages representing the entire lifespan of
      this animal species. Results from this study indicate that production of
      antinuclear antibodies, anticell extract antibodies and natural autoantibodies
      gradually and significantly increases from young age to old age without a
      corresponding increase in neither serum immunoglobulin concentration nor in
      levels of selected markers of immune dysregulation (sTNF-RI, sTNF-RII, IL-2 sR
      alpha and IFN-gamma). Therefore, in the baboon model, autoantibodies may be
      produced in absence of recognizable pathological conditions of the ageing immune
      system.

PMID- 11298121
TI  - Involvement of the ERK mitogen-activated protein kinase in cell resistance to
      complement-mediated lysis.
AB  - Sublytic doses of complement desensitize cells and make them resistant to lytic
      complement doses. This process, named complement-induced protection, requires
      calcium ion influx, protein kinase C activation and protein synthesis. The
      involvement of the extracellular signal-regulated kinase, ERK, in cell
      desensitization by sublytic complement was examined in erythroleukaemia K562
      cells and in COS-7 cells. As shown here, ERK is activated in K562 and COS-7 cells
      within 10 min of sublytic immune attack and then shows a decline and a second
      peak of activation at 20 min. C7- and C8-deficient human sera have a small effect
      on ERK activity. However, a significant increase in ERK activation is observed
      when C7 or C8, respectively, is added back to these sera. Complement-induced ERK
      activation was blocked in cells treated with GF109203X or Go6976, two selective
      PKC inhibitors, as well as by treatment with PD098059, an inhibitor of MEK1, the
      ERK kinase. PD098059 treatment also sensitized K562 cells to complement-mediated
      lysis and prevented complement-induced protection. COS-7 cells transfected with a
      dominant-negative MEK plasmid were incapable of undergoing the process of
      complement-induced protection. In conclusion, cell desensitization by sublytic
      doses of the complement membrane attack complex involves a signalling cascade
      that includes PKC-mediated ERK activation.

PMID- 11298122
TI  - A defect in bone marrow derived dendritic cell maturation in the nonobesediabetic
      mouse.
AB  - The pathogenesis of diabetes in the nonobese diabetic (NOD) mouse is
      characterized by a selective destruction of the insulin-producing beta-cells in
      the islets of Langerhans mediated by autoreactive T cells. The function of T
      cells is controlled by dendritic cells (DC), which are not only the most potent
      activators of naive T cells, but also contribute significantly to the
      establishment of central and peripheral tolerance. In this study, we demonstrate
      that the NOD mouse (H2: K(d), Ag(7), E*, D(b)) shows selective phenotypic and
      functional abnormalities in DC derived from bone marrow progeny cells in response
      to GM-CSF (DC(NOD)). NOD DC, in contrast to CBA DC, have very low levels of
      intracellular I-A molecules and cell surface expression of MHC class II, CD80,
      CD86 and CD40 but normal beta 2-microglobulin expression. Incubation with the
      strong inflammatory stimulus of LPS and IFN-gamma does not increase class II MHC,
      CD80 or CD86, but upregulates the level of CD40. The genetic defect observed in
      the DC(NOD) does not map to the MHC, because the DC from the MHC congenic
      NOD.H2(h4) mouse (H2: K(k), A(k), E(k), D(k)) shares the cell surface phenotype
      of the DC(NOD). DC from these NOD.H2(h4) also fail to present HEL or the
      appropriate HEL-peptide to an antigen-specific T cell hybridoma. However all the
      DC irrespective of origin were able to produce TNF-alpha, IL-6, low levels of IL
      12(p70) and NO in response to LPS plus IFN-gamma. A gene or genes specific to the
      NOD strain, but outside the MHC region, therefore must regulate the
      differentiation of DC in response to GM-CSF. This defect may contribute to the
      complex genetic aetiology of the multifactorial autoimmune phenotype of the NOD
      strain.

PMID- 11298123
TI  - Intradermal skin test with diabetes specific antigens in patients with type 1
      diabetes.
AB  - Cell mediated immune response in vitro to a number of antigens has been reported
      in patients with Type 1 diabetes. The aim of the present study was to develop an
      in vivo intradermal (delayed type hypersensitivity) skin test using antigens
      known to be recognized by lymphocytes of patients with Type 1 diabetes and to
      compare, where possible, the in vivo response to the in vitro T cell
      proliferation to the same antigens. The skin test was performed in the following
      group of patients: 55 with recent onset Type 1 diabetes; 16 patients with Type 1
      diabetes of longer duration; 10 patients with autoimmune thyroid disease and 20
      patients with Latent Autoimmune Diabetes in Adults (LADA). Type 1 diabetes
      specific antigens for the skin test included glutamic acid decarboxilase (GAD65),
      insulin and beta casein, whereas diabetes non specific antigens included tetanus
      toxoid, diphteria, proteus, tubercolin, streptococcus, and glycerol as control. A
      multitest device consisting of heads delivering intradermally 10 microl of
      solution containing the antigens was applied to the forearms; the specific
      antigens were injected in one forearm whereas the non specific antigens were
      injected in the other forearm. Reading of the reaction, which was considered
      positive in the presence of a nodule of 2 mm diameter was performed 48 h after
      the multitest application. The in vitro T cell response to diabetes specific
      antigens used in the multitest was studied using conventional proliferation
      assays in patients with recent onset Type 1 diabetes and in age matched normal
      subjects. Only recent onset Type 1 diabetes patients showed an in vivo positive
      response to GAD65, such response being detectable in 10 patients (18%). Two
      patients reacted also to beta casein and insulin, all other patient groups
      resulted negative but 2 patients with longer duration of Type 1 diabetes. There
      was no apparent link between the in vivo skin test and in vitro T cell
      proliferation to GAD65. We conclude that in vivo cell mediated immune reaction to
      GAD65, insulin and beta casein can be visualized in a minority of patients with
      recent onset Type 1 diabetes. Further studies are required to determine
      specificity and whether altering the dose can improve the sensitivity of the
      test.

PMID- 11298124
TI  - Differential binding of IgG and IgA antibodies to antigenic determinants of
      bovine serum albumin.
AB  - The aim of this study was to investigate the recognition pattern of bovine serum
      albumin (BSA), a major dietary protein by serum IgG and IgA antibodies. Anti-BSA
      IgG and IgA antibodies were measured by ELISA technique in 3 different cohorts:
      578 unselected persons, 84 new-onset insulin-dependent diabetes mellitus (IDDM)
      patients and 103 atopic persons. In order to characterize the recognition pattern
      of the different BSA domains, recombinant BSA and recombinant fragments covering
      the 3 BSA domains were produced. BSA digestion was monitored in simulated gastric
      fluid experiments by means of domain specific monoclonal antibodies. IgG and IgA
      antibody titres to native BSA were highest in IDDM patients. The three major BSA
      domains were equally well recognized by IgG antibodies of the three cohorts.
      Interestingly all three study groups showed a dissociation of their IgG and IgA
      antibody response to the first BSA domain. The ratio of IgG to IgA antibodies
      recognizing this domain was 93%/42% in controls, 92%/37% in IDDM patients and
      80%/47% in atopic persons. In simulated gastric fluid experiments, the first BSA
      domain was the first to become undetectable to specific monoclonal antibodies
      during digestion. In conclusion humoral IgG and IgA antibodies recognize the
      major BSA domains with different frequencies. The N-terminal domain of BSA, the
      first to be degraded during simulated gastric digestion is less well recognized
      by IgA antibodies. This suggests that early digestion is negatively correlated to
      the IgA antibody response and that the IgA response associated to the gut
      associated lymphoid tissue (GALT) and the systemic IgG antibody responses are
      independent.

PMID- 11298125
TI  - Activation of signal-transducer and activator of transcription 1 (STAT1) in
      pouchitis.
AB  - Activation of signal transducer and activator of transcription 1 (STAT1) is a
      hallmark of IFN-gamma receptor signal transduction but is also part of the
      signalling pathway of other cytokines/growth factor receptors. In ulcerative
      colitis, high levels of activation and expression of STAT1 have been observed in
      comparison with both Crohn's Disease and normal controls. Pouchitis develops in
      some patients after Ileal-Pouch-Anal-Anastomosis (IPAA). The pathophysiology and
      aetiology of pouchitis is still unclear. Recent studies have shown an increased
      production of proinflammatory cytokines including IFN-gamma. To investigate the
      expression and activation of STAT1 in pouchitis and the influence of treatment,
      patients were followed longitudinally from pouch operation. Diagnosis of
      pouchitis was made by clinical, endoscopic and histological criteria. Biopsies
      were obtained during routine endoscopy and snap frozen in liquid nitrogen.
      Nuclear and cytosolic extracts were prepared and the expression and activation of
      specific transcription factors were assessed by Western blot, electrophoretic
      mobility shift assay and immunofluorescence. Patients who develop pouchitis show
      highly increased levels of STAT1 alpha as well as STAT1 beta expression and
      activation in comparison with both normal pouch and normal ileal mucosa.
      Improvement of pouchitis during antibiotic therapy relates to a normalization of
      STAT1 expression and activation. We conclude that activation of STAT1 correlates
      to clinical disease activity and therefore STAT1 could play an important role in
      the pathophysiology of pouchitis. Similarities in the pattern of activation of
      STAT1 in pouchitis and ulcerative colitis may suggest a common pathway in the
      immunopathophysiology of both diseases.

PMID- 11298126
TI  - Flow cytometric measurement of HLA-DR expression on circulating monocytes in
      healthy and sick neonates using monocyte negative selection.
AB  - The aim of this study was to investigate the effect of prematurity, neonatal
      sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte
      HLA-DR expression of neonates using a flow cytometric method based on monocyte
      negative selection. The subjects were one hundred and thirty-one neonates (59
      healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20
      healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR
      labelling in a gate for monocytes obtained using the combination of CD3-CD19-
      PE/CD15--FITC MoAbs. In addition, the common dual staining method using MoAbs
      against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR
      labelling higher purity and recovery values of monocytes were achieved than with
      the dual labelling METHOD: Healthy neonates had significantly lower percentages
      of HLA-DR(+) monocytes than adults (69 +/- 13% versus 91.5 +/- 2.5%) and
      comparable mean fluorescence intensity (MFI) (119 +/- 25 versus 131 +/- 26).
      Values did not differ significantly between healthy term and preterm neonates.
      Preterm neonates with RDS had a significantly lower percentage of HLA-DR(+)
      monocytes than the healthy preterm neonates. In neonates with asphyxia both
      parameters were comparable to those of the healthy ones. Septicaemic neonates
      presented significantly lower values of both parameters than the healthy, RDS and
      asphyxiated neonates. Monocyte negative selection provides a reliable estimation
      of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in
      healthy neonates in comparison with adults and is further decreased in neonates
      with sepsis and RDS, but it is not influenced by prematurity and perinatal
      asphyxia.

PMID- 11298127
TI  - Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated
      monocytes.
AB  - Secondary amyloidosis (AA amyloidosis) is a systemic disease characterized by the
      extracellular tissue deposition of insoluble amyloid A (AA) protein. Aberrant
      metabolism of serum amyloid A (SAA) by macrophages is only one of many putative
      mechanisms which may be important in AA amyloidogenesis. In this study, we
      investigated the effects of cytokines on human monocyte-mediated SAA proteolysis.
      Human peripheral blood mononuclear cells (PBMC) or CD14(+) monocytes were
      cultured with SAA, and the culture supernatants were then subjected to anti-SAA
      immunoblot. CD14(+) monocytes degraded SAA completely. Whereas, when CD14(+)
      monocytes were pretreated with IL-1 beta or IFN-gamma, increasing amounts of SAA
      related derivatives were detected in culture supernatants. These findings suggest
      that activation of monocytes by IL-1 beta or IFN-gamma hampers the proteolysis of
      a precursor protein and leads to a partial degradation of SAA. This down
      regulated proteolysis of SAA protein by cytokine-stimulated monocytes may play a
      role in the mechanism of AA amyloid formation as well as its removal.

PMID- 11298128
TI  - The impact of platelet-activating factor (PAF)-like mediators on the functional
      activity of neutrophils: anti-inflammatory effects of human PAF-acetylhydrolase.
AB  - Platelet-activating factor (PAF) is a proinflammatory agent in infectious and
      inflammatory diseases, partly due to the activation of infiltrating phagocytes.
      PAF exerts its actions after binding to a monospecific PAF receptor (PAFR). The
      potent bioactivity is reflected by its ability to activate neutrophils at
      picomolar concentrations, as defined by changes in levels of intracellular Ca(2+)
      ([Ca(2+)](i)), and induction of chemotaxis and actin polymerization at nanomolar
      concentration. The role of PAF in neutrophil survival is, however, less well
      appreciated. In this study, the inhibitory effects of synthetic PAFR-antagonists
      on various neutrophil functions were compared with the effect of recombinant
      human plasma-derived PAF-acetylhydrolase (rPAF-AH), as an important enzyme for
      PAF degradation in blood and extracellular fluids. We found that endogenously
      produced PAF (-like) substances were involved in the spontaneous apoptosis of
      neutrophils. At concentrations of 8 microg/ml or higher than normal plasma
      levels, rPAF-AH prevented spontaneous neutrophil apoptosis (21 +/- 4% of
      surviving cells (mean +/- SD; control) versus 62 +/- 12% of surviving cells (mean
      +/- SD; rPAF-AH 20 microg/ml); P < 0.01), during overnight cultures of 15 h. This
      effect depended on intact enzymatic activity of rPAF-AH and was not due to the
      resulting product lyso-PAF. The anti-inflammatory activity of rPAF-AH toward
      neutrophils was substantiated by its inhibition of PAF-induced chemotaxis and
      changes in [Ca(2+)](i). In conclusion, the efficient and stable enzymatic
      activity of rPAF-AH over so many hours of coculture with neutrophils demonstrates
      the potential for its use in the many inflammatory processes in which PAF (-like)
      substances are believed to be involved.

PMID- 11298129
TI  - Polarized secretion of CXC chemokines by human intestinal epithelial cells in
      response to Bacteroides fragilis enterotoxin: NF-kappa B plays a major role in
      the regulation of IL-8 expression.
AB  - Enterotoxigenic B. fragilis, which produces a approximately 20 kD heat-labile
      toxin (BFT), has been associated with diarrhoeal diseases and mucosal
      inflammation. To determine if epithelial cells can contribute to BFT-induced
      inflammation, we assessed the expression of CXC chemokines by BFT-stimulated
      human intestinal epithelial cells. BFT stimulation increased expression of the
      neutrophil chemoattractant and activators ENA-78, GRO-alpha, and IL-8. Up
      regulated chemokine mRNA expression was paralleled by increased protein levels.
      Activation of the IL-8 and NF-kappa B transcriptional reporters was inhibited in
      cells cotransfected with the I kappa B kinase beta and IkB alpha superrepressor
      plasmids. Whereas lactate dehydrogenase, which was used to monitor cell lysis,
      was released predominantly from the apical surface, CXC chemokines were
      predominantly secreted from the basolateral surface of BFT-treated epithelial
      cells. The basolateral secretion of CXC chemokines from BFT-stimulated colon
      epithelial cells suggests that these chemokines can contribute to the
      inflammatory cell infiltrate in the underlying intestinal mucosa.

PMID- 11298130
TI  - Effect of oestrogen on Mycobacterium avium complex pulmonary infection in mice.
AB  - The purpose of the present study was to elucidate the role of oestrogen in the
      pathogenesis of Mycobacterium avium complex (MAC) pulmonary disease, which occurs
      most frequently in postmenopausal women. The study was carried out in a murine
      infectious model using ovariectomized DBA/2 female mice. Infection with MAC was
      established by intratracheal administration of bacilli. In some experiments,
      ovariectomized mice were treated with exogenous 17 beta-estradiol (E2). The
      number of bacilli in the lungs of infected mice which received ovariectomy was
      significantly larger than that in the lungs of sham-operated control mice, and
      treatment of ovariectomized mice with exogenous E2 restored the burden of bacilli
      to the same level as that in the sham-operated control mice. We next examined the
      effect of E2 in vitro using bone marrow-derived macrophages obtained from DBA/2
      female mice. The macrophages showed bacteriostatic activity against MAC after
      treatment with interferon-gamma (IFN-gamma) and this activity was further
      enhanced by the exogenous addition of E2 to the culture medium. In parallel with
      these findings, E2 augmented the production of reactive nitrogen intermediates
      (RNI) by macrophages pretreated with IFN-gamma and stimulated with MAC, as shown
      by evaluating nitrite production and inducible nitric oxide synthase mRNA
      expression. These findings taken together suggest that absence of endogenous
      oestrogen appears to be responsible for the development of MAC pulmonary disease
      in this mouse model and that the enhancement by E2 of anti-MAC activity of murine
      macrophages induced through increased RNI production may play some role in
      resistance to MAC infection.

PMID- 11298131
TI  - Increased Mycobacterium tuberculosis growth in HIV-1-infected human macrophages:
      role of tumour necrosis factor-alpha.
AB  - Synergism between Mycobacterium tuberculosis (M. tuberculosis) and HIV-1
      infections was demonstrated in several in vitro models and clinical studies.
      Here, we investigated their reciprocal effects on growth in chronically HIV-1
      infected promonocytic U1 cells and in acutely infected monocyte-derived
      macrophages (MDM). Phagocytosis of M. tuberculosis induced HIV-1 expression in U1
      cells, together with increased TNF-alpha production. M. tuberculosis growth,
      evaluated by competitive PCR, was greater in HIV-1-infected MDM compared to
      uninfected cells. M. tuberculosis phagocytosis induced greater TNF-alpha and IL
      10 production in HIV-1-infected MDM than in uninfected cells. In uninfected MDM,
      addition of TNF-alpha and IFN-gamma decreased, whereas IL-10 increased M.
      tuberculosis growth. On the contrary, in HIV-1-infected MDM, addition of TNF
      alpha and IFN-gamma increased, whereas IL-10 has no effect on M. tuberculosis
      growth. TNF-alpha seems to play a pivotal role in the enhanced M. tuberculosis
      growth observed in HIV-1-infected MDM, being unable to exert its physiological
      antimycobacterial activity. Here, for the first time we demonstrated an enhanced
      M. tuberculosis growth in HIV-1-infected MDM, in line with the observed clinical
      synergism between the two infections.

PMID- 11298132
TI  - Reduced HIV-stimulated T-helper cell reactivity in cord blood with short-course
      antiretroviral treatment for prevention of maternal-infant transmission.
AB  - T-helper cell responses to HIV have been associated with protection against
      maternal-infant HIV transmission in the absence of antiretroviral treatment, but
      the effects of antiretroviral treatment, now widely used for prevention, on
      development of these cell-mediated responses is unknown. We tested whether
      development of T-helper cell responses to HIV and other antigens would be
      affected by exposure to short-course regimens of zidovudine-lamivudine (ZDV-3TC)
      given to prevent maternal-infant HIV transmission. Cord blood samples were
      collected from 41 infants of HIV-infected mothers enrolled in a clinical trial in
      which they were treated with regimens of ZDV-3TC and from 29 infants whose HIV
      infected mothers were not treated with any antiretroviral drugs. T-helper cell
      reactivity to HIV envelope peptides and other antigens was measured in vitro
      using a sensitive culture supernatant titration assay based on IL-2-dependent
      proliferation. Infants in the clinical trial were followed to 18 months to
      determine their HIV infection status, and venous blood samples were re-tested at
      4.5 and 9 months for T-cell reactivity to HIV. HIV-stimulated T-helper cell
      reactivity in cord blood was detected 10-fold less frequently among those exposed
      to antiretroviral prophylaxis (2.4%) than among those unexposed (24.1%) (P =
      0.007). Reductions in HIV-stimulated responses in cord blood occurred despite
      detectable HIV RNA (mean 3.38 standard deviation 0.76 log(10) copies per ml) at
      delivery among treated women and occurred independent of treatment duration. Our
      results suggest that short-course antiretroviral treatment given to prevent
      maternal-infant HIV transmission may attenuate HIV-stimulated T-cell memory
      responses in the neonate.

PMID- 11298133
TI  - Lack of evidence for the Th2 predominance in patients with chronic hepatitis C.
AB  - A T helper (Th)1 to Th2 shift has been proposed to be a critical pathogenic
      determinant in chronic hepatitis C. Here, we evaluated mitogen-induced and
      hepatitis C virus (HCV) core antigen-induced cytokine production in 28 patients
      with biopsy-proven chronic hepatitis C. Flow cytometry demonstrated that after
      mitogenic stimulation the percentage of Th2 cells (IL-4 + or IL-13 +) and Th0
      cells (IFN-gamma/IL-4 + or IL-2/IL-13 +) did not differ between patients and
      controls. In contrast, the percentage of Th1 cells (IFN-gamma + or IL-2 +) was
      significantly increased in CD4 +, CD8 +, 'naive'-CD45RA + and 'memory'-CD45RO + T
      cell subsets from patients versus controls. Similar results were obtained by
      ELISA testing supernatants from mitogen-stimulated, unfractionated peripheral
      blood mononuclear cell (PBMC) cultures. Interferon-alpha treatment was associated
      with a reduction in the mitogen-induced Th1 cytokine response in those patients
      who cleared their plasma HCV-RNA. Analysis of cytokine expression by CD4 + T
      cells after HCV core antigen stimulation in a subgroup of 13 chronic hepatitis C
      patients demonstrated no cytokine response in 74% of these patients and an IFN
      gamma-restricted response in 26%. Finally, no Th2 shift was found in
      lipopolysaccharide-stimulated monocytes. These data indicate that a Th1 to Th2
      shift does not occur in chronic hepatitis C.

PMID- 11298134
TI  - Treatment with ribavirin and interferon-alpha reduces interferon-gamma expression
      in patients with chronic hepatitis C.
AB  - Recent studies in vitro and in animals have suggested that ribavirin may
      potentiate the antihepatitis C virus (HCV) activity of interferon-alpha (IFN
      alpha) by up-modulating the production of T cell-derived cytokines, such as
      interleukin (IL)-2 and IFN-gamma, which play a key role in the cellular immune
      response against HCV. To study the immune-modulatory mechanisms of ribavirin
      further, cytokine production by activated T cells and circulating cytokine levels
      were studied by FACS analysis and ELISA testing in 25 patients with chronic
      hepatitis C unresponsive to IFN-alpha, before and after treatment with either
      ribavirin plus IFN-alpha or IFN-alpha alone. After 16 weeks of treatment, both
      the expression of IFN-gamma by activated T cells and the blood levels of IFN
      gamma, were significantly reduced with respect to pretreatment values in patients
      treated with ribavirin and IFN-alpha but not in those undergoing treatment with
      IFN-alpha alone. The expression of IFN-gamma was significantly lower in patients
      that gained normal ALT levels with respect to those that did not. No modification
      of the expression of IL-2, IL-4 and IL-10 was found before and after treatment in
      either group of patients. In conclusion, the results of this study do not support
      up-modulation of IFN-gamma and IL-2 production as the mechanism by which
      ribavirin potentiates IFN-alpha anti HCV activity. In addition, our findings
      suggest that ribavirin may exert an anti-inflammatory effect and may help
      reducing IFN-gamma-driven T cell activation and liver damage.

PMID- 11298135
TI  - Mapping of the antigenic determinants of the T. cruzi kinetoplastid membrane
      protein-11. Identification of a linear epitope specifically recognized by human
      Chagasic sera.
AB  - The high variability among strains and isolates of Trypanosoma cruzi and the
      existence of shared antigenic determinants with other pathogens, particularly
      with members of the Leishmania genus make difficult the specific diagnosis of
      Chagas' disease. The data reported in this paper show that the T. cruzi KMP11
      protein is an immunodominant antigen highly recognized by the sera from chagasic
      and leishmaniasis patients. By the use of amino- and carboxyl-terminal truncated
      KMP11 recombinant proteins and synthetic peptides, evidence is provided that
      while the sera from chagasic patients recognize linear peptides the sera from
      patients with visceral leishmaniasis must be predominantly directed against
      conformational epitopes. We found that a particular linear determinant, located
      in the carboxyl-terminal region of the protein, is recognized with high
      specificity and sensitivity only by sera from Chagas' disease patients,
      suggesting it could be a good candidate for differential serodiagnosis of Chagas'
      disease.

PMID- 11298136
TI  - Novel mutations and defective protein kinase C activation of T-lymphocytes in
      ataxia telangiectasia.
AB  - Three ataxia telangiectasia (AT) patients have been characterized immunologically
      and molecularly. Patient 1 presents two nondescribed splicing mutations which
      affect exons 15 and 21 of the ATM gene. The maternal defect consists of a G > A
      transition in the first nucleotide of the intron 21 donor splicing site which
      results in a complete deletion of exon 21. The paternal mutation consists of an A
      > C transversion in the intron 14 acceptor splicing site which produces a partial
      skipping of exon 15. Two abnormal alternative transcripts were found,
      respectively, 17 and 41 nucleotides shorter. Patient 2 presents a homozygous
      genomic deletion of 28 nucleotides in the last exon of the gene. This deletion
      changes the normal reading frame after residue 3003 of the protein and introduces
      a premature stop codon at residue 3008 that could originate a truncated ATM
      protein. Patient 3, a compound heterozygote, presents a defect which consists of
      a G > A transition in the first nucleotide of intron 62 donor splicing site which
      results in a complete deletion of exon 62. The results obtained during a three
      year period in the proliferation assays show an impaired PMA (phorbol myristate
      acetate) activation in specific T lymphocyte activation pathways (CD69, CD26,
      CD28, CD3, PHA, PWM and Con A mediated) but not in others (CD2, ionomycin, and Ig
      surface receptor). The possible link among specific ATM mutations and abnormal
      immune responses is unknown.

PMID- 11298137
TI  - Expression of RCAS1 and FasL in human trophoblasts and uterine glands during
      pregnancy: the possible role in immune privilege.
AB  - Pregnancy is an immunological balancing act. Trophoblasts do not express MHC
      class I or II, except HLA-C and G, but express Fas ligand (FasL), which confers
      immune privilege. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells)
      has recently been recognized to play a role in immune evasion of the tumour
      cells. We therefore studied the involvement of RCAS1 and FasL in the infiltration
      of NK cells by examining the curettaged uterine contents of 20 cases of early
      stage of pregnancy. The cases were clinically divided into two groups; curettage
      was performed (A) due to the absence of foetal heart beats, and (B) due to
      spontaneous uterine bleeding and abortion. In group A, RCAS1 was expressed in the
      uterine glands and extravillous cytotrophoblasts, as was FasL. Infiltration of NK
      cells around the uterine glands was scarcely detected. In contrast, in group B,
      expression of both RCAS1 and FasL was strikingly decreased in both the level of
      expression and the numbers of RCAS1/FasL-positive cells and massive infiltration
      of NK cells was frequently detected around the uterine glands. These findings
      suggest that a reduction in RCAS1 and FasL expression seems to be closely
      associated with activation and infiltration of maternal NK cells and destruction
      of uterine glands, resulting in rejection of the foetus. Thus, expression of
      RCAS1 and FasL in the uterine glands and cytotrophoblasts may play a role in the
      downregulation of the maternal immune response, thereby maintaining pregnancy at
      early stage.

PMID- 11298138
TI  - Cytokine expression and synovial pathology in the initiation and spontaneous
      resolution phases of adjuvant arthritis: interleukin-17 expression is upregulated
      in early disease.
AB  - The aim of this study was to understand the immune processes controlling the
      initiation and spontaneous resolution of adjuvant arthritis (AA). We investigated
      synovial T-cell recruitment and mRNA expression of IL-17 and other important
      disease related cytokines, IFN-gamma, IL-2, IL-4, TNF and TGF-beta in inguinal
      lymph node (ILN) and synovial membrane (SM). Arthritis severity was assessed by a
      numerical rating score and rats were sacrificed every 3--4 days postadjuvant
      induction. Further assessment involved quantitative radiology and histology of
      the ankle joints on each day, and the ILN and SM were removed for RNA extraction.
      Cytokine mRNA expression was measured using RT-PCR and densitometry. Paraffin
      sections of rat ankle joints were stained for T-cells (CD3) by
      immunohistochemistry. In the ILN, there was an increase in IL-17, TNF and IFN
      gamma expression in the early stages of disease, with a secondary sustained
      increase in IFN-gamma expression. In the SM, there was expression of T-cell
      cytokines in early arthritis (day 13), and prolonged TNF and TGF-beta expression,
      which reflected disease progression. IL-4 mRNA expression increased in the later
      stages of AA. Synovial T-cell numbers transiently increased at day 6, and
      remained high from days 13--28. Increased pro-inflammatory cytokine expression,
      including IL-17, in the ILN reflects the initiating events in the early stage of
      disease. IL-17 may therefore play an important role in the pathogenesis of AA.
      The increase in IL-4 (an anti-inflammatory cytokine) in the SM in the later
      stages of AA suggests that IL-4 is involved in the spontaneous resolution of AA.
      The initial increase in IFN-gamma in the ILN may reflect a pro-inflammatory
      response, while the prolonged secondary increase may indicate activation of
      regulatory T-cells.

PMID- 11298139
TI  - Differential requirements for induction of total immunoglobulin and physiological
      rheumatoid factor production by human peripheral blood B cells.
AB  - Rheumatoid factors (RFs) are autoantibodies directed against the Fc part of IgG.
      Considerable evidence exists that there are two classes of RFs, pathological and
      physiological. Whereas pathological RFs are associated with disease,
      physiological RFs are considered to be a normal component of the immune response.
      RF(+) precursor B cells present as part of the B cell repertoire of healthy
      individuals are held responsible for the production of physiological RFs, which
      is a transient phenomenon with a clear correlation with an initiating stimulus
      such as immunization or exposure to an infection. Here we demonstrate a
      difference in the regulatory control of total Ig and RF production by peripheral
      blood (PB) B cells of both healthy controls (HC) and patients with rheumatoid
      arthritis (RA). Highly purified B cells from HC and patients with RA were
      cocultured with T cells stimulated with immobilized anti-CD3 mAb. Similar to IgM
      production, IgM-RF production was shown to be dependent on CD40 cross-linking.
      However, activation of PB B cells in the CD40 system in the presence of IL-2, IL
      4, IL-10, combinations of these cytokines or supernatant of anti-CD3-stimulated T
      cells failed to induce detectable IgM-RF, whereas total IgM production was
      considerable. From these results we conclude that conditions to activate
      physiological RF(+) B cells require additional contact besides CD40--CD40L
      interactions between T and B cells. Since the requirements for RF production were
      similar using PB B cells from HC and patients with RA it is suggested that the
      regulatory properties of RF(+) precursors in the PB B cell compartment is equal
      among these groups. Together, these results indicate that conditions for the
      induction of total Ig and physiological RFs are different.

PMID- 11298140
TI  - Pathogenic function of IL-1 beta in psoriasiform skin lesions of flaky skin
      (fsn/fsn) mice.
AB  - IL-1 acts on many cells as an inflammatory mediator. Its two forms, IL-1 alpha
      and IL-1 beta, are regulated differentially within hyperproliferative
      inflammatory skin conditions, such as psoriasis. While IL-1 alpha is down
      regulated within psoriatic lesions, the levels of IL-1 beta are increased.
      However, some investigators have described an inactive form of IL-1 beta in
      psoriasis, while others have detected increased IL-1 beta activity within these
      lesions. Thus, its in vivo role remains unclear. We have assessed expression and
      function of IL-1 beta within psoriasiform skin lesions of the spontaneous mouse
      mutation flaky skin (fsn/fsn ). It was found that IL-1 beta was increased by 357%
      within psoriasiform lesions of fsn/fsn mice compared with their wild-type or
      heterozygous (+/?) littermates (P < 0.00001). When the IL-1 beta function was
      inhibited by i.p. injection with a neutralizing MoAb, no effects were seen in +/?
      mice. In contrast, psoriasiform features in fsn/fsn mice were alleviated
      dramatically, as demonstrated by a 40% decrease of the epidermal thickness and a
      diminished number of intra-epidermal microabscesses. In addition, infiltrating
      epidermal CD4(+) and CD8(+) T cells were decreased by 68% and 81%, respectively
      (P < 0.05), and epidermal Langerhans cells also were reduced by 36% (P < 0.005).
      In contrast, mast cells were not affected, suggesting differential responses of
      various cutaneous cell types. Our results demonstrate an important in vivo role
      of IL-1 beta for the generation of hyperproliferative inflammatory skin lesions
      in the fsn/fsn model.

PMID- 11298141
TI  - Non FcR-binding murine antihuman CD3 monoclonal antibody is capable of productive
      TCR signalling and induces proliferation in the presence of costimulation.
AB  - CLB T3/4.A is a non FcR-binding CD3 mAb of the murine IgA isotype, which may be
      used as an alternative for the mitogenic OKT3 mAb in the treatment of acute
      cellular rejection after organ transplantation. We studied TCR signalling and T
      cell activation in response to T3/4.A in normal human PBMC in vitro. T3/4.A
      induced a rapid rise in free cytoplasmic Ca(2+), not different from the response
      to mitogenic CD3 mAb. However, protein tyrosine phosphorylation and,
      particularly, MAPK activation, were reduced as compared to mitogenic CD3 mAb.
      T3/4.A enhanced expression of both CD69 and CD25, but proliferation and
      detectable cytokine production did not occur. Addition of either CD28 mAb or IL-2
      induced a strong proliferative response, which was accompanied by cytokine
      production. At higher mAb concentrations, T cell activation decreased, which
      correlated with TCR downmodulation. To exclude the possibility that activation by
      T3/4.A depends on interaction of murine IgA Fc with as yet unknown FcR, we showed
      that also with CD3 mAb F(ab')2 fragments upregulation of activation molecules
      occurred, as well as proliferation in the presence of costimulation. We conclude
      that the non FcR-binding murine IgA mAb T3/4.A acts as a partial agonist and
      leads to proliferation and cytokine production only in the presence of
      appropriate costimuli. These findings may explain the mitigated cytokine release
      syndrome observed in vivo with some nonmitogenic CD3 mAbs.

PMID- 11298142
TI  - Comparison of antimicrobial susceptibility test breakpoints of national
      societies.

PMID- 11298143
TI  - Evaluation of six commercial assays for the rapid detection of Clostridium
      difficile toxin and/or antigen in stool specimens.
AB  - OBJECTIVE: To evaluate six commercially available assays for the detection of
      Clostridium difficile toxin and/or antigen in stool samples: one latex
      agglutination test (Culturette brand CDT, Becton Dickinson), two ELISAs
      (Culturette brand Toxin CD, Becton Dickinson, and Ridascreen C. difficile Toxin
      A/B, R-biopharm), two chromatographic assays (Clearview C. difficile A, Oxoid,
      and ColorPac Toxin A, Becton Dickinson) and one enzyme immunoassay for the
      simultaneous detection of C. difficile common antigen and toxin A (Triage C.
      difficile Panel, Biosite). METHODS: Over a period of 3 months, 366 liquid or semi
      liquid stool samples were tested using cell-culture cytotoxin assay as standard,
      ethanol shock stool culture and latex agglutination (Culturette brand CDT). Of
      these, 78 samples, positive with at least one of these three methods, and 98
      randomly selected negative samples were further evaluated using the other five
      kits. PCR was also performed on positive cultures to confirm the presence of
      toxin A and B genes. RESULTS: Triage C. difficile Panel had the best sensitivity
      (95%), followed by Clearview C. difficile and ColorPac Toxin A (both 89%),
      Culturette brand Toxin CD (73%), Ridascreen C. difficile Toxin A/B (57%) and
      Culturette brand CDT (23%). For Triage, the sensitivity of C. difficile antigen
      detection was 93%, and the sensitivity of toxin detection was lower (77%). Most
      false-positive results were obtained with the Triage C. difficile Panel (25
      specimens) and Clearview C. difficile A (20 specimens). Culturette brand CDT had
      the best specificity (99%); followed by Ridascreen C. difficile Toxin A/B (97%),
      Culturette brand Toxin CD (95%), ColorPac Toxin A (89%), Clearview C. difficile A
      (83%) and Triage C. difficile Panel (75%). The positive predictive values ranged
      from 68% to 94%, and the negative predictive values from 83% to 98%. CONCLUSIONS:
      The sensitivity is much higher for Triage and the two new chromatographic assays
      than for the conventional EIAs. These tests also have a high negative predictive
      value. For Triage, C. difficile antigen-positive, toxin A-negative results can be
      obtained; the clinical value of these must be established by additional studies.
      Overall, the new-generation assays are still less sensitive than the cytotoxin
      assay; however, they provided same-day results, could be used as a screening test
      and may be useful in laboratories without tissue-culture facilities. Our results
      do not allow the recommendation of one single assay for the diagnosis of C.
      difficile-associated diarrhea. It remains the case that laboratory results must
      be correlated and interpreted with the clinical presentation of the patient.

PMID- 11298144
TI  - Uptake and intracellular activity of ketolide HMR 3647 in human phagocytic and
      non-phagocytic cells.
AB  - OBJECTIVE: To evaluate the uptake of HMR 3647 into human neutrophils (PMNs),
      human peritoneal macrophages (PMOs) and tissue-cultured cells (epithelial cells
      and fibroblasts), and to assess the intracellular activity of this drug. METHOD:
      Cell uptake of HMR 3647 was measured by radiometric assay, as described by
      Klemper and Styrt. Intracellular activity was determined by incubation for 3 h of
      PMNs containing bacteria in the presence of HMR 3647. RESULTS: The intracellular
      concentrations were 130 and 71 times higher than extracellular concentrations in
      PMNs and PMOs, respectively (extracellular concentrations: 2-25 mg/L). The
      cellular-to-extracellular concentration ratios (C/E) for tissue-cultured cells
      were lower than those obtained in phagocytic cells but still greater than 5. The
      uptake of HMR 3647 was rapid and non-saturable in all cells. HMR 3647 was
      released slowly from phagocytic cells. HMR 3647 (extracellular concentration: 0.5
      10 mg/L) did not significantly reduce the intracellular survival rate of
      Staphylococcus aureus ATCC 25923 in PMNs. CONCLUSIONS: HMR 3647 reaches
      intracellular concentrations several times higher than extracellular
      concentrations within phagocytic and non-phagocytic cells. The slow efflux of
      this drug from phagocytic cells suggests that these cells may be a vehicle for
      it, delivering it to sites of infection.

PMID- 11298145
TI  - The effect of acetazolamide on the kinetics of four newer beta-lactams in the
      aqueous humor.
AB  - OBJECTIVE: To evaluate whether the effect of acetazolamide on piperacillin's
      aqueous humor concentrations observed in animals exists also in humans for
      ceftazidime, cefotaxime, ceftriaxone and aztreonam. METHODS: One hundred and
      eighty-eight patients undergoing eye cataract surgery were randomly allocated to
      receive intravenous ceftazidime, cefotaxime, aztreonam or ceftriaxone with
      (subgroup A) or without (subgroup B) concomitant oral administration of
      acetazolamide. Antibiotic concentrations in serum and the aqueous humor,
      simultaneously sampled during the operation, were measured using an agar well
      diffusion technique, and the ratios of the concentrations of aqueous humor to
      serum were calculated and compared. Statistical analysis was performed by using
      the paired t-test. RESULTS: Mean aqueous humor ceftazidime concentrations at 2, 4
      and 6 h were 24.65, 16.4 and 8.6 mg/L (subgroup A), and 4.26, 8.66 and 5.61 mg/L
      (subgroup B). Corresponding concentrations of cefotaxime were 1.75, 1.0 and 0.77
      mg/L (subgroup A), and 1.11, 0.81 and 0.58 mg/L (subgroup B), and of aztreonam
      6.9, 5.84 and 3.61 mg/L (subgroup A), and 3.38, 2.57 and 1.48 mg/L (subgroup B).
      Ceftriaxone concentrations at 2, 4, 6 and 12 h were 1.78, 1.49, 1.57 and 1.41
      mg/L (subgroup A), and 1.35, 0.95, 1.08 and 0.85 mg/L (subgroup B). The
      differences in aqueous humor concentrations when acetazolamide was administered
      were statistically significant (P < 0.05), with the exception of ceftazidime 6 h,
      cefotaxime 6 h and ceftriaxone 2 h. CONCLUSIONS: Although acetazolamide resulted
      in statistically significant increases in the aqueous humor concentrations of all
      the antibiotics tested, this effect was most marked for ceftazidime.

PMID- 11298146
TI  - Survival of Coxiella burnetii within free-living amoeba Acanthamoeba castellanii.
AB  - OBJECTIVE: To determine whether Coxiella burnetti is able to survive within free
      living amoeba. METHODS: When C. burnetii was co-cultivated with the free-living
      amoeba species Acanthamoeba castellanii. RESULTS: Viable bacteria were detected
      for 18 days. Microscopic studies confirmed the presence of bacteria within
      vacuoles, some of which appeared to be spore-like forms. CONCLUSION: These
      results indicate that free-living amoebae could provide an intracellular niche
      for the spore formation and survival of C. burnetii in the environment.

PMID- 11298147
TI  - Tick-borne bacterial diseases emerging in Europe.
AB  - Since the identification of Borrelia burgdorferi as the agent of Lyme disease in
      1982, 11 tick-borne human bacterial pathogens have been described throughout
      Europe. These include five spotted fever rickettsiae, the agent of human
      granulocytic ehrlichiosis, four species of the B. burgdorferi complex and a new
      relapsing fever borrelia. We present these emerging diseases and focus on the
      factors that play a role in the recognition of new tick-borne diseases.

PMID- 11298148
TI  - Clinical microbiological case: a Nicaraguan woman with skin lesions on the left
      elbow and foot.

PMID- 11298149
TI  - Modified Hodge and EDTA-disk synergy tests to screen metallo-beta-lactamase
      producing strains of Pseudomonas and Acinetobacter species.

PMID- 11298150
TI  - Herpes zoster in non-hospitalized children.

PMID- 11298151
TI  - Quality control parameters for cefditoren susceptibility tests.

PMID- 11298152
TI  - Campylobacter lari bacteremia.

PMID- 11298153
TI  - Evolution of TEM beta--lactamase genes identified by PCR with newly designed
      primers in Korean clinical isolates.

PMID- 11298154
TI  - Rhodotorula septicemia: case report and minireview.

PMID- 11298155
TI  - Catheter-related bacteremia due to Ewingella americana.

PMID- 11298156
TI  - Vibrio alginolyticus acute gastroenteritis: report of two cases.

PMID- 11298157
TI  - Driving and vertigo.

PMID- 11298158
TI  - Epstein-Barr virus infectious mononucleosis.
AB  - The Epstein-Barr virus (EBV) is the aetiological agent of classical infectious
      mononucleosis. This review article describes the antigenicity of the virus, the
      specific antibody response and the stimulated polyclonal heterophile antibody
      production in the host. The diagnostic tests for EBV infection are discussed,
      with particular attention drawn to the pitfalls of the Monospot test.
      Complications are listed and management strategies are outlined. The uses and
      complications of steroids are discussed. The importance of avoidance of contact
      sport and the association with splenic rupture is described.

PMID- 11298159
TI  - The effect of the nasal cycle on mucociliary clearance.
AB  - The nasal cycle is a well-recognised physiological phenomenon where each side of
      the nose alternates through phases of congestion and decongestion. Although many
      physiological properties of the nose alternate with the nasal cycle whether this
      has any effect on the nasal mucociliary clearance is less clear. As the nose is a
      potential site for the administration of pharmaceuticals, it is essential that
      any factors that could affect clearance (and hence absorption) are identified.
      This study set out to investigate if mucociliary clearance rates differed between
      the clear and obstructed airway at a morning peak of the nasal cycle in five
      healthy volunteers with normal nasal anatomy using a dual-radioisotope labelling
      procedure that allows both sides of the nose to be assessed simultaneously. The
      clearance of the radiopharmaceutical formulations from the nasal cavity was
      monitored using gamma scintigraphy and decay-adjusted 50%-clearance times were
      calculated for each nostril. The ratios of clearance times from the patent
      nostril when compared to the obstructed nostril were statistically significant
      (two-tailed t-test; P = 0.039), the mean ratio being 2.5 : 1 (SEM +/- 0.5). It
      can be concluded that the nasal cycle has a marked effect on the mucociliary
      clearance patterns of the nose. This may have both theoretical and practical
      implications for the nasal delivery of drugs.

PMID- 11298160
TI  - Surgical landmarks of the spinal accessory nerve in modified radical neck
      dissection.
AB  - We designed a study to identify useful landmarks for the preservation of the
      spinal accessory nerve during modified radical neck dissection (MRND). Eighteen
      consecutive patients undergoing 23 MRNDs were enrolled in the study. The distance
      of the accessory nerve from the greater auricular nerve, where it crosses the
      posterior edge of the sternocleidomastoid muscle (greater auricular point), was
      noted. The vertical distance between the point of entrance of the accessory nerve
      into the trapezius muscle and the clavicle was also measured. The mean distance
      between the greater auricular point and the accessory nerve was 10.7 mm, SD +/-
      6.3. In all cases the accessory nerve was above the greater auricular point. The
      mean distance between the point of entrance of the nerve into the trapezius and
      the clavicle was 51.3 mm, SD +/- 17. The greater auricular point is a reliable
      landmark for the identification of the accessory nerve during modified radical
      neck dissection. Distance above the clavicle was less helpful.

PMID- 11298161
TI  - The sense of coherence: a tool for evaluating patients with peripheral vestibular
      disorders.
AB  - Peripheral vestibular disorders may result in physical as well as psychosocial
      dysfunction. Such a situation demands a capacity to cope which lately has been
      discussed as an important factor in the health outcome. Antonovsky has described
      the concept of sense of coherence (SOC) as such a trait and has developed a
      questionnaire (the SOC Scale) to measure it. The aim of this study was to
      describe the patients' self-rated degree of SOC and to set this in relation to
      their perception of the self-rated quality of life. The results showed that
      patients with a strong SOC scored statistically less self-rated handicap, less
      emotional distress, less impact on working capacity and sleep and rest and less
      psychosocial dysfunction than those with weak SOC scores. It is suggested that
      the SOC Scale may serve as a tool to identify patients who are at risk of poorer
      quality of life and in need of supportive care.

PMID- 11298162
TI  - The efficacy of topical anaesthesia in flexible nasendoscopy: a double-blind
      randomised controlled trial.
AB  - The routine use of topical anaesthesia during flexible nasendoscopy has been
      questioned, and the degree to which topical vasoconstrictors can affect patient
      discomfort has yet to be elucidated. Patients' experiences with Lignocaineand
      phenylephrine, Lignocaine alone, xylometazoline and no preparation were compared.
      One hundred patients were recruited in this double-blind, randomised control
      trial and put into these four groups. Each patient completed a visual analogue
      scoring chart to determine the severity of unpleasantness and other undesirable
      effects (pain, bad taste, burning, choking, numbness and difficulty in
      swallowing). The results confirmed that vasoconstriction is a major contributing
      factor towards reducing overall unpleasantness (P = 0.022), topical anaesthesia
      can produce a bad taste (P = 0.022), and that none of the preparations have any
      effect on the pain during nasendoscopy. In conclusion, xylometazoline is
      recommended for nasendoscopy as it is effective and is significantly cheaper than
      the other preparations. Not using any preparations leads to the experience of
      severe symptoms.

PMID- 11298163
TI  - Objective assessment of hoarseness by measuring jitter.
AB  - The objective measurement of hoarseness by measuring 'jitter' (the average
      percentage pitch-period variation between consecutive pitch-cycles) using an
      inverse filtering technique is described. Twenty-five patients with a variety of
      causes of hoarseness were studied, together with five individuals who had mild
      hoarseness induced by histamine challenge and 12 normal individuals. The mean
      severity of jitter in the patient group (9.8%) was significantly different from
      the normals. (1.04%) In addition, there was a significant correlation (R2 = 0.53;
      P < 0.0001) between jitter and subjective assessment of hoarseness. The mean
      values of jitter with histamine challenge before and after recovery (1.03%, and
      1.18%) were significantly different (P < 0.0001) to the mean maximum value during
      the challenge (2.64%). These data suggest that jitter is an objective and
      repeatable measurement of hoarseness-even small changes in hoarseness in
      individual patients. It is likely to prove most effective for monitoring
      treatment response.

PMID- 11298164
TI  - Major complications and consent prior to endoscopic sinus surgery.
AB  - The endonasal endoscopic approach to the paranasal sinuses is no longer
      exclusively practised by a small number of dedicated super-specialists and has
      gained widespread acceptance in the UK. We have audited the practice of the
      Consultant members of the BAO-HNS via a confidential postal questionnaire with
      regards to the consent of their patients prior to surgery, and to the
      complications they have experienced. The overall rate of complications following
      endoscopic sinus surgery (ESS) was 0.69%, with the incidence of major
      complications 0.25% and of minor complications 0.44%. Wide variations in the
      practice of informed consent were found to exist, and this is discussed with
      reference to a suggested template for preoperative discussion with the patient.

PMID- 11298165
TI  - The accuracy of MEDLINE and Journal contents pages for papers published in
      Clinical Otolaryngology.
AB  - MEDLINE is widely used as a source for identifying and reviewing medical journal
      literature. Its accuracy is generally taken for granted, as is that of the
      contents pages published by the journals themselves. In this study of citation
      accuracy we examined the articles published in Clinical Otolaryngology and Allied
      Sciences from 1976 to 1998. The entries in MEDLINE were compared with the entries
      in the Journal's contents pages, and with the actual articles. Of 1651 articles
      published in the journal, one was omitted from MEDLINE and 25 (1.5%) were
      incorrectly cited, while 88 (5.3%) were incorrectly cited in the contents pages.
      Twenty-one (84%) of the errors in MEDLINE involved names of authors. Apart from
      incomplete retrieval of information for practice and research, errors could
      result in an author not getting credit for publications.

PMID- 11298166
TI  - A comparison of sleep quality in normal children and children awaiting
      (adeno)tonsillectomy for recurrent tonsillitis.
AB  - Poor quality sleep and sleep-related hypoxia have been described in children
      awaiting (adeno)tonsillectomy even in the absence of a history which would
      suggest such problems. However, restless sleep has also been commonly reported in
      children from a normal population. It has not been shown whether an increasing
      frequency of tonsillitis is associated with deterioration in sleep quality. This
      study directly compares sleep quality in three groups of children: (1) a normal
      population; (2) children from a normal population who have tonsillitis but are
      not awaiting tonsillectomy; and (3) children awaiting tonsillectomy for recurrent
      tonsillitis. A questionnaire was completed by the parents and the answers
      compared using the chi2 and Spearman's rank correlation tests. The results show
      that children awaiting tonsillectomy have poorer sleep quality than their normal
      peers. However, there is no dose-response effect between deteriorating sleep
      quality and increasing frequency of tonsillitis.

PMID- 11298167
TI  - Patient eligibility for day case paediatric adenotonsillectomy.
AB  - There is a growing trend towards day case surgery and departments are constantly
      under pressure from Health Trusts to perform more day case procedures.
      Adenoidectomy and tonsillectomy are being performed as day case procedures in
      many centres and literature has suggested that it is safe to do so, provided the
      population characteristics are favourable. A prospective study of 100 consecutive
      patients presenting to our department for tonsillectomy or adenotonsillectomy was
      undertaken to assess the eligibility of our patient group for day surgery.
      Medical and social history was obtained as per recommended guidelines. Only 27%
      of our patients were eligible for day surgery and only 17% of parents preferred
      the option of day case adenotonsillectomy. There is a marked difference between
      our group and those previously reported in the literature. This regional
      variation has implications in the safe expansion of day surgical procedures.

PMID- 11298168
TI  - Patient benefit from functional and cosmetic rhinoplasty.
AB  - The Glasgow Benefit Inventory, a validated post-interventional questionnaire, was
      used to determine patient benefit from septorhinoplasty according to indication
      (function, cosmesis or a combination) in 87 patients. We showed a very
      significant patient benefit from this procedure and have demonstrated that the
      benefit is greatest when cosmesis is an indication (P = 0.05).

PMID- 11298169
TI  - Heating of air in the nasal airways in patients with chronic sinus disease before
      and after sinus surgery.
AB  - The main goal of this study was to determine the influence of sinus surgery on
      the heating of inspired air in the nose. Intranasal temperature values of 22
      patients with chronic sinus disease were measured after inspiration at different
      locations in the nasal cavity. Measurements were done before and 6-8 weeks after
      sinus surgery. The patients were compared to 22 healthy control subjects. Nasal
      airway temperature did not differ between the two study groups at any location in
      the nasal cavity. Nasal decongestion was without significant influence on
      temperature values in the patients and the volunteers. There was no significant
      difference of nasal airway temperature before and after sinus surgery. Even after
      sinus surgery the main area of heating of inspired air seemed to be the anterior
      part of the nose. Sinus surgery in patients with chronic sinus disease does not
      seem to influence heating of air in the nasal cavity.

PMID- 11298171
TI  - The future of anaesthesiology.

PMID- 11298170
TI  - A comparison of surgery and radiotherapy in the management of advanced pyriform
      fossa carcinoma.
AB  - This retrospective study analyses the outcome of treatment of 61 patients with
      advanced carcinoma of the pyriform fossa. Thirty-two patients (group 1) underwent
      surgery and postoperative radiotherapy and 29 patients (group 2) had induction
      chemotherapy followed by radiotherapy. The local recurrence-free survival at 5
      years from the completion of therapy for group 1 was 54%, compared to 61% for
      group 2. The 5-year neck recurrence-free survival for groups 1 and 2 were 54% and
      59%, respectively. The 5-year overall survival rates for groups 1 and 2 were 19%
      and 14%, respectively. Non-surgical therapy for advanced stage pyriform fossa
      cancer provides survival comparable with that achieved with the standard approach
      of surgery and postoperative radiotherapy. We advocate radical irradiation as the
      method of choice because it provides nodal coverage to the bilateral jugular
      chains and retropharyngeal nodes, all known to be at risk for metastases, and is
      associated with lower morbidity compared to surgery. But, however, despite the
      therapy, the outcome is poor.

PMID- 11298172
TI  - Anaesthetic care for sickle cell disease.
AB  - Despite the high frequency of sickle cell disease in Europe, the disease is
      poorly managed. Critical periods are the hospital stays during which the
      anaesthesiologist plays an important role. Understanding the molecular basis of
      polymerization processes of haemoglobin S can help to avoid triggering a crisis.
      Differentiation of the various haemoglobin phenotypes helps to estimate the
      individual perioperative risk. Knowledge of the patient's history and the actual
      haemoglobin S level facilitates general anaesthesia, surgery and postoperative
      care. Damage to liver, spleen, eyes, bones, lung and central nervous system
      increases the perioperative risk. Preoperative preparation includes early
      admission, intravenous volume substitution, continuing pain therapy and
      prophylactic antibiotic medication. General anaesthesia seems to be better for
      patients with a high-risk profile rather than regional anaesthesia. Careful
      perioperative and postoperative monitoring should allow hypoxaemia, hypovolaemia,
      hypothermia, acidosis and overtransfusion to be avoided. Effective pain therapy
      includes a combination of opioids with peripherally acting analgesia.

PMID- 11298173
TI  - The influence of intravenous anaesthetics on the activity of enzymes released
      from polymorphonuclear leucocytes in vitro.
AB  - BACKGROUND AND OBJECTIVE: Polymorphonuclear leucocytes make a decisive
      contribution to defence against bacterial infections. In particular, the effects
      of anaesthetics on non-oxidative bactericidal mechanisms have previously only
      been superficially examined. Although the influence of anaesthetic agents on
      oxidative bactericidal activity has been thoroughly examined, our study
      concentrated on the effect on non-oxidative processes, which appears to have been
      a neglected field of research. METHODS: The effects of methohexital, etomidate,
      ketamine, fentanyl and morphine on the activity of lysozyme and beta
      glucuronidase released from polymorphonuclear leucocytes have been studied in
      vitro. The activity of lysozyme was determined by recording the changes in the
      turbidity of a suspension of micrococcus lysodeicticus caused by the enzymatic
      action of lysozyme. beta-glucuronidase activity was photometrically measured by
      the enzymatic cleavage of phenolphthalein glucuronic acid. RESULTS: High
      concentrations of methohexital inhibited lysozyme activity; however, etomidate
      and morphine caused an increase of beta-glucuronidase activity in therapeutic
      plasma concentrations. While there was no effect of etomidate on lysozyme
      activity, all concentrations tested significantly stimulated beta-glucuronidase
      activity. This result was unexpected because intravenous anaesthetics have
      previously shown a tendency to suppress polymorphonuclear leucocyte functions.
      Whereas the inhibition of lysozyme activity by the high concentration of
      methohexital was no surprise, the increase of beta-glucuronidase activity caused
      by etomidate, ketamine, fentanyl and morphine was quite unexpected. CONCLUSIONS:
      At present, the underlying mechanism for the increase of beta-glucuronidase
      activity caused by etomidate, ketamine, fentanyl and morphine is unknown. The
      fact that there was no influence of these agents on lysozyme activity possibly
      suggests that the anaesthetic agents have different effects on azurophilic and
      specific granules. Since in vitro investigations have their limitations, it is
      too early to draw practical consequences from our study. Moreover, at present it
      is unclear whether an increase of beta-glucuronidase activity in vivo is an
      advantage or not. In any case, we think it advisable to perform further
      investigations on the influence of anaesthetic agents on oxygen-independent
      bactericidal mechanisms.

PMID- 11298174
TI  - Postoperative titration of intravenous morphine.
AB  - BACKGROUND AND OBJECTIVE: Intravenous morphine titration is used to obtain
      postoperative pain relief, but few studies have assessed the appropriate regimen.
      In a quality programme, we performed a prospective non-randomized study of
      morphine titration in a postanaesthesia care unit (PACU). METHODS: Four regimens
      of morphine titration were studied: every 10 (group 1, n = 400) or 5 min (group
      2, n = 400) with a maximum of five intravenous boluses; every 5 min, without any
      limitation in the number of boluses (groups 3 and 4, n = 400 each); in groups 1,
      2, and 3, subcutaneous morphine was administered 4 h after titration. In group 4,
      administration of subcutaneous morphine was allowed only 2 h after titration. A
      visual analogue pain scale (VAPS) > 30 mm was required to administer morphine and
      pain relief was defined as a VAPS < or = 30 mm. RESULTS: After morphine
      titration, VAPS was lower and the number of patients with pain relief was greater
      in patients from groups 3 and 4. Patients from group 4 had the lowest VAPS (26 +/
      17 mm) and the highest percentage of pain relief (73%) at the end of the PACU
      period. The number of sedated patients increased in groups 3 (62%) and 4 (61%)
      compared with group 1 (27%). No significant differences in morphine-related
      adverse effects were observed. CONCLUSION: Intravenous morphine titration every 5
      min with an unlimited number of boluses and early subcutaneous administration
      provided the best analgesic regimen.

PMID- 11298175
TI  - Midazolam reduces the dose of propofol required for induction of anaesthesia and
      laryngeal mask airway insertion.
AB  - BACKGROUND AND OBJECTIVE: Insertion of the laryngeal mask airway in the
      anaesthetized patient can sometimes be difficult and propofol has been advocated
      as the anaesthetic induction agent of choice because of its depressant effect on
      laryngeal reflexes compared with other intravenous anaesthetics. However, when
      used as the sole induction agent, relatively large doses of propofol are required
      to achieve successful laryngeal mask insertion. This has cost implications and
      may produce unwanted cardiorespiratory depression. METHODS: One hundred and forty
      two patients were randomized to receive either: fentanyl 1 microg kg(-1) and
      lidocaine 1.5 mg kg(-1) (group 1), or fentanyl 1 microg kg(-1) and midazolam 0.04
      mg kg(-1) (group 2), or fentanyl 1 microg kg(-1), midazolam 0.04 mg kg(-1) and
      lidocaine 1.5 mg kg(-1) (group 3) or fentanyl 1 microg kg(-1) (group 4) 2 min
      before induction of anaesthesia. Anaesthesia was established with propofol
      infused at 33.3 mg min(-1). RESULTS: Patients who were given midazolam required
      significantly less propofol to achieve satisfactory laryngeal mask insertion,
      median propofol doses: group 1, 1.63 mg kg(-1); group 2, 1.16 mg kg(-1); group 3,
      1.01 mg kg(-1); group 4, 1.9 mg kg(-1), P < 0.0001 (analysis of variance).
      Patients given midazolam reported less pain on injection with propofol 13% and 3%
      groups (2 and 3) compared with 37.5% and 77% (groups 1 and 4) P = 0.002 (chi(2)).
      CONCLUSIONS: Midazolam reduces the dose of propofol required for induction of
      anaesthesia and successful insertion of the laryngeal mask airway. There was no
      clinical benefit to be gained from the addition of lidocaine.

PMID- 11298176
TI  - High doses of mepivacaine for brachial plexus block in patients with end-stage
      chronic renal failure. A pilot study.
AB  - BACKGROUND AND OBJECTIVE: Patients with end-stage chronic renal failure are at
      risk of developing several serious postanaesthetic complications. Many
      anaesthesiologists perform brachial plexus anaesthesia with high doses of local
      anaesthetic in order to achieve an extensive blockade of the upper limb. Brachial
      plexus block is a suitable technique for anaesthesia for creation, repair or
      removal of vascular access for haemodialysis. The aim of this study was to
      measure mepivacaine plasma concentrations after axillary block with 650 mg plain
      mepivacaine in patients with end-stage chronic renal failure. METHODS:
      Mepivacaine plasma concentrations were assessed throughout a 150-min period, in
      10 patients after axillary block with 650 mg plain mepivacaine (600 mg for
      axillary block and 50 mg for supplementation). RESULTS: Mepivacaine plasma
      concentrations expressed in microg mL(-1) as medians and their ranges were: 1.69
      (1.23--7.78) at 5 min, 5.61 (4.36--8.19) at 30 min, 8.28 (3.83--11.21) at 60 min,
      7.93 (5.63--11.1) at 90 min and 6.49 (5.56--8.35) at 150 min without any symptoms
      of toxicity. CONCLUSIONS: Brachial plexus anaesthesia with 650 mg plain
      mepivacaine did not result in serious systemic toxicity in these patients despite
      the high mepivacaine plasma concentrations found.

PMID- 11298177
TI  - Ketamine and propofol differentially inhibit human neuronal K(+) channels.
AB  - BACKGROUND AND OBJECTIVE: Interaction of intravenous anaesthetic agents with
      voltage-dependent potassium channels significantly correlates with clinical
      concentrations. If potassium channels were to play an important part in
      anaesthesia, one might expect different effects at the molecular level of those
      anaesthetics that show different clinical effects. Our aim was to analyse the
      interaction of general anaesthetics with voltage-dependent K channels. METHODS:
      Whole cell patch-clamp experiments were analysed in detail in order to compare
      the effects of two clinically diverse intravenous hypnotics, ketamine and
      propofol, on voltage-dependent potassium channels in human neuroblastoma SH-SY5Y
      cells. RESULTS: Both anaesthetics inhibited the potassium conductance in a
      concentration-dependent and reversible manner with IC50-values of 300 microM and
      45 microM for ketamine and propofol respectively. Whereas ketamine shifted the
      midpoint of current activation by maximally 14 mV to more hyperpolarized
      potentials, propofol had the opposite effect on the activation midpoint. Current
      inhibition by ketamine increased with voltage but decreased with propofol at
      higher membrane potentials. Propofol but not ketamine induced concentration
      dependent but voltage-independent decline, akin to inactivation, of the voltage
      dependent potassium channels. CONCLUSIONS: The anaesthetics differed not only in
      their clinical profiles but they also showed differential actions on voltage
      dependent potassium channels in several ways. This provides additional evidence
      for the hypothesis that voltage-dependent potassium channels play an important
      role in anaesthesia.

PMID- 11298178
TI  - Effects of cibenzoline on cardiac function and metabolism in the rat heart--lung
      preparation.
AB  - BACKGROUND AND OBJECTIVE: Although there is concern that cibenzoline, an
      antidysrhythmic drug for the treatment of ventricular and supraventricular
      dysrhythmias, may be associated with dose-dependent inhibition of myocardial
      contractility there are few reports about the relationship between myocardial
      metabolism and cardiac function when it is used. The present study was designed
      to investigate the effects of cibenzoline on cardiac function and metabolism. The
      effects of cibenzoline on cardiac function and myocardial metabolism were
      assessed in the isolated rat heart-lung preparation. METHODS: Thirty-two male
      Wistar-ST rats were divided into four groups: control, and those to receive
      cibenzoline, either 300, 900 or 3000 ng mL(-1). The cibenzoline was administered
      into the perfusate 5 min after the start of perfusion. Heart rates in the 3000 ng
      mL(-1) group were significantly lower than those in the control group. Cardiac
      output in the 3000 ng mL(-1) group at 15 and 30 min was significantly lower than
      in the control group. In all groups, values for %LV dP/dt max (the ratio of
      values at each time to those at 5 min) at 20, 25, 30 min were significantly
      higher than at 5 min. Myocardial adenosine triphosphate concentration in the 3000
      ng mL(-1) group was significantly lower than in controls. There was no difference
      between groups in the lactate/pyruvate ratio. CONCLUSION: The therapeutic range
      of cibenzoline has few effects on cardiac function and metabolism, although
      concentrations 10 times greater may cause a deterioration in myocardial
      metabolism.

PMID- 11298179
TI  - Negative pressure pulmonary oedema after cryotherapy for tracheal obstruction.
AB  - We report a patient who suffered negative pressure pulmonary oedema because of
      tracheal obstruction after cryotherapy to granulation tissue in the trachea. The
      pathophysiology and clinical course of negative pressure pulmonary oedema is
      described. Though there are reports of negative pressure pulmonary oedema after
      airway obstruction, to our knowledge this is the first case reported after
      cryotherapy.

PMID- 11298181
TI  - From which countries do chairpersons and invited speakers at important
      anaesthesia and intensive care meetings come?

PMID- 11298182
TI  - Rapid glycine absorption secondary to pressurization of irrigation fluid during
      transcervical endometrial resection.

PMID- 11298185
TI  - Metabolic cardiomyopathies.
AB  - The energy needed by cardiac muscle to maintain proper function is supplied by
      adenosine Ariphosphate primarily (ATP) production through breakdown of fatty
      acids. Metabolic cardiomyopathies can be caused by disturbances in metabolism,
      for example diabetes mellitus, hypertrophy and heart failure or alcoholic
      cardiomyopathy. Deficiency in enzymes of the mitochondrial beta-oxidation show a
      varying degree of cardiac manifestation. Aberrations of mitochondrial DNA lead to
      a wide variety of cardiac disorders, without any obvious correlation between
      genotype and phenotype. A completely different pathogenetic model comprises
      cardiac manifestation of systemic metabolic diseases caused by deficiencies of
      various enzymes in a variety of metabolic pathways. Examples of these disorders
      are glycogen storage diseases (e.g. glycogenosis type II and III), lysosomal
      storage diseases (e.g. Niemann-Pick disease, Gaucher disease, I-cell disease,
      various types of mucopolysaccharidoses, GM1 gangliosidosis, galactosialidosis,
      carbohydrate-deficient glycoprotein syndromes and Sandhoff's disease). There are
      some systemic diseases which can also affect the heart, for example
      triosephosphate isomerase deficiency, hereditary haemochromatosis, CD 36 defect
      or propionic acidaemia.

PMID- 11298186
TI  - Osteopontin: a key cytokine in cell-mediated and granulomatous inflammation.
AB  - Osteopontin (Opn) is a secreted adhesive, glycosylated phosphoprotein that
      contains the arginine-glycine-aspartic acid (RGD) cell-binding sequence that is
      found in many extracellular matrix (ECM) proteins (for a review of Opn see
      References Denhardt & Guo 1993; Patarca et al. 1993; Rittling & Denhardt 1999).
      Since its initial description in 1979 as a secreted protein associated with
      malignant transformation, Opn has been independently discovered by investigators
      from diverse scientific disciplines, and has been associated with a remarkable
      range of pathologic responses. Opn is an important bone matrix protein, where it
      is thought to mediate adhesion of osteoclasts to resorbing bone. However, studies
      from the past decade have identified an alternative role for Opn as a key
      cytokine regulating tissue repair and inflammation. Recent work by our laboratory
      and that of others has underlined the importance of Opn as a pivotal cytokine in
      the cellular immune response. Despite this Opn is not well known to the
      immunologist. In this review we will focus on studies that pertain to the role of
      Opn in cell-mediated and granulomatous inflammation.

PMID- 11298187
TI  - Subtractive hybridization--genetic takeaways and the search for meaning.
AB  - Gene expression profiling relies on mRNA extraction from defined cell systems,
      which in the case of pathological processes necessarily results in the use of
      small quantities of tissues, sometimes as little as a few cells. This obviates
      the use of many systems of gene expression profiling and is best carried out
      using cDNA amplified by poly(A) reverse transcription polymerase chain reaction,
      which is capable of generating material representative of all the expressed genes
      in samples as small as one cell. Analysis of this material using subtractive
      hybridization compares the genes expressed at different stages of a
      biological/pathological process allowing identification of the all the genes
      upregulated during the process. The identification of the genes present is not
      dependent on their prior description or on the choice of genes used in a screen
      and as such the method is ideal for identifying novel genes or unsuspected genes.
      We have used the method to identify genes involved in normal osteoblastic
      differentiation and in Paget's disease of bone and it has been widely used to
      study normal differentiation and pathological processes in a number of systems.
      The method, its applications and its relationship with the other methods of gene
      expression profiling are reviewed.

PMID- 11298189
TI  - Constitutively synthesized nitric oxide is a physiological negative regulator of
      mammalian angiogenesis mediated by basic fibroblast growth factor.
AB  - We recently reported that the systemically administered nitric oxide synthase
      (NOS) inhibitor Nw-nitro-L-arginine methyl ester, L-NAME, administered before,
      during and after the angiogenic treatment stimulated angiogenesis induced by
      basic fibroblast growth factor, bFGF, in the rat. This suggests that suppression
      of constitutively expressed NOS, cNOS, plus inducible NOS, iNOS, and thus reduced
      production of nitric oxide, NO, was the stimulating factor. In those studies, the
      rat mesenteric-window angiogenesis assay was used. Moreover, the systemic
      administration of a NO releaser inhibited bFGF-mediated angiogenesis. Using the
      same experimental system, we have now studied whether the inhibition of cNOS
      alone in adult animals under physiological conditions, i.e. prior to the
      administration of the angiogenic stimulation with bFGF, affected the subsequent
      angiogenic response. cNOS constitute endothelial cell NOS (ecNOS) and neuronal
      NOS (nNOS). L-NAME or its inactive enantiomer Nw-nitro-D-arginine methyl ester, D
      NAME, were given continuously in the drinking water (1.0 g/L) during 14 days
      prior to the start of the treatment with bFGF. The treatment with L-NAME
      significantly enhanced the subsequent angiogenic response. NO synthesized under
      physiological conditions by ecNOS in endothelial cells and platelets or nNOS in
      platelets may thus act as a first constitutional angiostatic factor in bFGF
      mediated mammalian angiogenesis.

PMID- 11298188
TI  - Calcitonin and calcitonin receptors: bone and beyond.
AB  - Calcitonin (CT), a 32 amino acid peptide hormone produced primarily by the
      thyroid, and its receptor (CTR) are well known for their ability to regulate
      osteoclast mediated bone resorption and enhance Ca2+ excretion by the kidney.
      However, recent studies now suggest that CT and CTRs may play an important role
      in a variety of processes as wide ranging as embryonic/foetal development and
      sperm function/physiology. In this review article, CT and CTR gene transcription,
      signal transduction and function are addressed. The effects of CT on the
      physiology of a variety of organ systems are discussed and the relationship
      between polymorphisms in the CTR gene and bone mineral density (BMD)/osteoporosis
      is examined. Recent studies demonstrating the ability of receptor activity
      modifying proteins (RAMPs) to post-translationally modify the calcitonin receptor
      like receptor (CRLR) are detailed and studies employing transgenic mouse
      technology to determine the temporal and tissue specific transcriptional activity
      of the CTR gene in vivo are discussed.

PMID- 11298190
TI  - Synergistic action of endothelin (ET)-1 on the activation of bronchial fibroblast
      isolated from normal and asthmatic subjects.
AB  - Bronchial subepithelial fibrosis is an histological characteristic of asthma.
      Cytokines and other mediators, such as PDGF-BB, TGF-beta1 and ET-1 found in the
      asthmatic submucosa can potentially activate a repair process that leads to
      fibroblast proliferation and collagen synthesis. The mechanisms of modulation of
      the repair process leading to extracellular matrix deposition are still to be
      documented. In this study, we assessed the in vitro proliferation and collagen
      synthesis of bronchial fibroblasts isolated from normal and asthmatic subjects in
      response to ET-1, platelet-derived growth factor (PDGF)-BB and transforming
      growth factor (TGF)-beta1 alone or in combination, in the presence or absence of
      dexamethasone. The combination of ET-1 with one of the other two growth factors,
      or the triple combination, significantly increased DNA synthesis and collagen
      production of bronchial fibroblasts isolated from both normal and asthmatic
      subjects, but the same growth factors used separately had no significant effect
      on the same parameters. These results suggest that the simultaneous presence of
      ET-1, PDGF-BB and TGF-beta1 in both normal and asthmatic subjects is necessary to
      activate bronchial fibroblast proliferation and collagen synthesis. As these
      mediators are present in the submucosa of the asthmatic bronchi, they could be
      responsible, at least in part, for the accumulation of collagen in the mucosa.

PMID- 11298193
TI  - Sources of support for older people after discharge from hospital: 10 years on.
AB  - AIMS OF THE STUDY: The aim of this research was to find out who supports older
      people at home after discharge from hospital and if sources of support have
      changed between the 1980s and the 1990s. BACKGROUND: More and more older people
      are being discharged from hospital earlier and this creates additional pressures
      on families, community health and social services and the independent care
      sector. The research was concerned with how sources of support may have changed
      in a 10-year period. METHODS: A comparison is made of two separate nonrandom
      samples, taken 10 years apart, of older people following discharge from hospital.
      Interviews were conducted in participants' homes to establish levels of
      dependence and the source of support given in response to the need for help with
      personal and domestic activities of daily living. RESULTS: Although limited by
      the use of relatively small, nonrandom samples, the research found that
      proportions needing help with domestic activities were higher than those needing
      help with personal activities of daily living. Although dependence for help with
      bathing had declined between the 1980s and 1990s, help was still needed with
      bathing and dressing. Unmet need for help with bathing remained a problem in the
      1990s. A growing role for home helps was identified, especially in personal care
      (bathing and dressing), where support from district nurses had declined. By the
      1990s, home helps were doing less cooking and housework, including heavy laundry.
      Relatives were doing more of most domestic activities except shopping, which was
      being carried out by home helps. CONCLUSIONS: The paper concludes by arguing that
      hospitals should consider if pressures to discharge older people more quickly
      might hinder the discharge planning process and communication between hospital
      and community sectors.

PMID- 11298192
TI  - The nature and effect of communication difficulties arising from interactions
      between district nurses and South Asian patients and their carers.
AB  - AIM: The overall aim of the study was to examine how policy directives concerning
      the provision of individualized care were modified in their transformation into
      practice and the implications this carried for the care provided to patients from
      different ethnic backgrounds. This paper is concerned with one aspect, namely,
      examining the nature and effects of communication difficulties between the nurses
      and South Asian patients and their carers. METHODS: An ethnographic approach was
      used. The study was undertaken in an English community National Health Service
      (NHS) Trust serving an ethnically diverse population. It comprised two stages.
      First, an organizational profile of the trust was undertaken in order to analyse
      the local policy context. Data were collected by means of in-depth interviews
      with managers and a review of policy documentation and caseload profiles. Second,
      a participant observational study was undertaken focusing on six district nursing
      teams. Purposive sampling was used to identify four teams with high ethnic
      minority caseloads and two teams with predominantly white ethnic majority
      caseloads. Interview transcripts and fieldnotes were analysed by drawing upon the
      principles of dimensional analysis. FINDINGS: Over half of South Asian patients
      had little or no understanding of spoken English with women and older people the
      least likely to speak English. The limited use of professional interpreters and
      the concomitant heavy reliance on family members to translate highlighted how
      ethnic minority patients and carers who were not fluent in English were
      disadvantaged. The observed language barriers suggested that the content of
      advice on matters such as compliance with treatment regimes might not be fully
      understood. Psychological support of patients and carers was severely restricted.
      Moreover, the fact that follow-up visits were on occasions made to patients for
      whom there was no one available to interpret constrained on-going assessment of
      patients' needs. CONCLUSIONS: The findings raise concerns regarding the quality
      of care provided to patients and carers who are nonusers of English and provide
      evidence of inequalities in service provision. However, not speaking English
      should not be a barrier to appropriate and effective nursing care. District
      nurses need to appreciate their responsibility to provide equitable services
      irrespective of a patient's linguistic background and seek to overcome the
      disadvantage experienced by ethnic minority patients.

PMID- 11298194
TI  - 'Chatting': an important clinical tool in facilitating mothering in neonatal
      nurseries.
AB  - AIM: This paper explores the use of 'chat' or 'social talk' as an important
      clinical tool that can assist nurses achieve family-centred care in neonatal
      nurseries. BACKGROUND: The study was undertaken to increase knowledge of women's
      experiences of mothering in the neonatal nursery and the relationship they share
      with nurses. METHOD: The discussion presented is elicited from a grounded theory
      analysis of over 60 hours of interview data with 28 women, a thematic analysis of
      50 hours of interviews with 20 nurses and a content analysis of 398 tape-recorded
      interactions between nurses and parents. FINDINGS: The analysis identifies the
      importance of the nurse-mother relationship and demonstrates that it is both the
      context and method by which nursing care is delivered. We found the verbal
      exchanges that take place between nurse and mother influence a woman's
      confidence, her sense of control and her feelings of connection to her infant. It
      appears from the data that the nurse's ability to effectively 'engage' the mother
      is dependent on the use of language that expresses care, support and interest in
      parents. CONCLUSIONS: The data suggests that 'chatting' is the strategy and the
      process through which positive interactions are initiated, maintained and
      enhanced. This study confirms that nurses' language acts as a powerful clinical
      tool that can be used to assist parents in gaining confidence in caring for their
      infants and in becoming 'connected' to infants resident in nurseries.

PMID- 11298195
TI  - Women's experiences of 'being diagnosed' with a long-term illness.
AB  - AIMS: In this paper we share women's storied accounts of 'being diagnosed' with a
      long-term illness. The purpose of the paper is to raise awareness of health
      professionals that receiving a medical diagnosis is a potentially calamitous
      event, challenging self-identity. BACKGROUND: The three authors were involved in
      three separate inquiries which explored women's experiences of living with
      illness. The authors realized that 'being diagnosed' was a common memorable event
      for the women across the inquiries. The literature around receiving a diagnosis
      was scarce. DESIGN: This paper is the result of secondary analysis of data from
      three different projects where we researched women living with long-term illness.
      In this paper, we focus on the experience of 'being diagnosed' as we share and
      show women's perceptions of receiving a medical diagnosis. FINDINGS: Receiving a
      medical diagnosis of a long-term illness was a memorable event in the women's
      lives. Many women felt alone with their illness, often without adequate
      information to find meaning in the relationship between their familiar self and
      their new identity as a woman living with illness. They felt vulnerable and lost
      as they tried to understand the meanings and consequences that the diagnosis held
      for their present and their future. Informational needs may be specific and
      individual. For many, receipt of a diagnostic label was momentous and should not
      be underestimated, despite the initial feeling of chaos, many women felt
      validated. CONCLUSION: Receiving a medical diagnosis is one event where health
      care professionals could be on standby. It is important to take the woman's
      articulation of the event seriously. Open, genuine communication, with
      willingness on behalf of the health professional to listen would be affirming for
      women who are coming to terms with the diagnosis of a chronic illness.

PMID- 11298196
TI  - Can a home-based pelvic examination be used in assessing reproductive morbidity
      in population-based studies? A Jordanian experience.
AB  - RATIONALE: Most estimates of reproductive morbidity in a community are derived
      from health service-based studies. However, these numbers do not reflect the
      actual magnitude of the problem because of barriers to health care and
      differences in health-seeking behaviour. As a result, this study uses an
      alternative method to measure reproductive morbidities amongst women in a
      Jordanian community. OBJECTIVE: To assess the validity of a home-based pelvic
      examination in detecting signs of reproductive morbidity when compared with a
      clinic-based examination. METHODOLOGICAL DESIGN: Descriptive study in which women
      were randomly selected from the study area to participate in the study. RESEARCH
      METHODS: Three hundred and seventy nine women, 18 years and above were randomly
      selected, and general and pelvic examinations were conducted in each woman's
      home. Thirty-two of these women were again randomly selected and consented to a
      second pelvic examination in a clinical setting. INSTRUMENTS: Two trained female
      obstetricians conducted the pelvic examination which included examination of the
      vulva, examination of the vagina and a bimanual examination. Outcome measures.
      Strength of association between the presence or absence of physical signs of
      reproductive morbidity detected by the home-based pelvic examination and the same
      signs identified by the clinic-based examination, deemed in this study as the
      'truth'. RESULTS: The overall sensitivity, specificity, positive and negative
      predictive values of the home-based pelvic examination were 66, 86, 69 and 84%,
      respectively. STUDY LIMITATIONS: The sample size was small, so further studies
      are recommended to replicate the findings here. CONCLUSIONS: Results suggest home
      based pelvic examinations can be used in population-based studies for a
      comprehensive assessment of women's reproductive morbidities.

PMID- 11298197
TI  - Menopause-associated problems: types and magnitude. A study in the Ain Al-Basha
      area, Jordan.
AB  - RATIONALE: To begin to fill the information gap on the health of menopausal women
      in developing countries. OBJECTIVES: Objectives were three fold: to establish an
      approximate age of onset of menopause for women in the study area; to report on
      the physical presence of certain physical conditions; and, to record the self
      reported frequency of signs/symptoms of menopause in the 6 months prior to the
      study. METHODOLOGICAL DESIGN: A descriptive study of women randomly sampled from
      the study community. RESEARCH METHODS: Women's homes were randomly sampled from
      the residential blocks surrounding the local community health centre. Women
      agreeing to the first phase of the study were also asked to consent to the second
      phase, then revisited to complete this second phase. INSTRUMENTS: The first phase
      of the study involved an in-depth semistructured questionnaire and the second
      phase, a general and pelvic examination with laboratory tests. OUTCOME MEASURES:
      To gather the information as set out under Objectives. RESULTS: One hundred and
      thirty seven women were included in the study. The median age of menopause was 49
      years. Women either reported or were found to be suffering from a variety of
      health problems including: urinary incontinence (37%), urinary tract infections
      (UTI) (11%), reproductive tract infections (RTI) (39%), and genital prolapse
      (41%). CONCLUSIONS: Menopausal women suffer from an appreciable level of
      morbidity as they approach menopause. Also, the level of health awareness of
      these women lags behind the identified prevalence of the studied conditions.

PMID- 11298198
TI  - The relationship between menstrual attitudes and menstrual symptoms among
      Taiwanese women.
AB  - AIM OF THE STUDY: This study explored characteristics of the menstrual cycle
      including duration, prevalence and severity of symptoms and examined the
      relationship of these characteristics with attitudes toward menstruation.
      BACKGROUND: Conceptualization of menstrual phenomena and attitudes toward
      menstruation may vary among cultures. While data about menstrual health among
      American women are widely available, there are little data concerning menstrual
      health in Taiwanese women. DESIGN/METHODS: A total of 30 healthy women with a
      mean age of 24.4 years participated in the study and made daily records of
      symptoms over a 90-day period with the Woods Daily Health Diary (WDHD). They then
      retrospectively completed the Moos Menstrual Distress Questionnaire (MMDQ) and
      the Menstrual Attitudes Questionnaire (MAQ). RESULTS: The mean age of menarche of
      these women was 13 years, their mean cycle duration was 5.8 days and the cycle
      length was 31.1 days. The mean scores of five subscales for MAQ ranged from 2.19
      to 3.28. Forty-six percent of the surveyed Taiwanese women agreed that the onset
      of menstruation can be predicted and anticipated, and 78% of these women agreed
      that menstruation was a natural event. CONCLUSIONS: Menstrual attitudes in
      Taiwanese women are multidimensional, and that significant cross-cultural
      differences are present. Attitudes toward menstruation in Taiwanese women are
      related to their physical, cognitive, behavioural and psychological changes in
      the premenstrual and menstrual phases.

PMID- 11298199
TI  - The concept of spiritual care in mental health nursing.
AB  - AIM: In this paper we aim to clarify the issue of spiritual care in the context
      of mental health nursing. BACKGROUND: The concept of spirituality in nursing has
      received a great deal of attention in recent years. However, despite many
      articles addressed to the issue, spiritual care remains poorly understood amongst
      nursing professionals and, as a result, spiritual needs are often neglected
      within the context of health care. METHODS: A series of focus groups was
      conducted to obtain the views of service users, carers and mental health nursing
      professionals about the concept of spirituality and the provision of spiritual
      care in mental health nursing. RESULTS: According to the views expressed in our
      focus groups, spiritual care relates to the acknowledgement of a person's sense
      of meaning and purpose to life which may, or may not, be expressed through formal
      religious beliefs and practices. The concept of spiritual care was also
      associated with the quality of interpersonal care in terms of the expression of
      love and compassion towards patients. Concerns were expressed that the ethos of
      mental health nursing and the atmosphere of care provision were becoming less
      personal, with increasing emphasis on the 'mechanics of nursing'. CONCLUSIONS:
      The perceived failure of service providers to attend adequately to this component
      of care may be symptomatic of a medical culture in which the more readily
      observable and measurable elements in care practice have assumed a prominence
      over the more subjective, deeply personal components. In order for staff to
      acknowledge these issues it is argued that a more holistic approach to care
      should be adopted, which would entail multidisciplinary education in spiritual
      care.

PMID- 11298200
TI  - Further testing of the Mental Health Problems Perception Questionnaire.
AB  - AIM OF THE STUDY: This paper reports a two-part study relating to the further
      psychometric development of the Mental Health Problems Perceptions Questionnaire.
      BACKGROUND: The instrument was developed and used originally in a study to
      investigate the role of district nurses in caring for people with mental health
      problems, who live in rural settings. It is underpinned by an explicit
      theoretical framework in which therapeutic commitment, role support and role
      competency are core concepts. DESIGN: A two-part study is described. Part One
      used a test-retest method to examine the stability of the instrument on repeated
      administration. Part Two examined the instrument's internal reliability and
      construct validity by calculation of Cronbach's alpha coefficients and
      exploratory factor analysis. RESULTS: Satisfactory internal reliability for a new
      instrument was demonstrated. Exploratory factor analysis supported the previously
      proposed theoretical framework. Significant correlations were demonstrated
      between the scales which constitute the instrument, thereby providing further
      evidence of construct validity. CONCLUSIONS: The Mental Health Problems
      Perceptions Questionnaire provides a potentially useful instrument in relation to
      future educational, clinical and managerial research.

PMID- 11298201
TI  - Simplified Japanese Self-Perception Scale for Young Adults (SJS-PSYA) to identify
      risk cases.
AB  - AIM: The purpose of this study was to investigate the effectiveness of the newly
      devised Simplified Japanese Self-Perception Scale for Young Adults (SJS-PSYA) for
      identifying risk cases. The SJS-PSYA was used to measure self-perception of young
      adults and its validity was examined. The subjects were 196 Japanese young adults
      (91 males, 105 females) who had participated in the longitudinal study of Ueda
      (1996, 1998) from infancy and preschool years to adolescence. METHOD:
      Questionnaires for subjects and their parents were mailed separately and then
      interviews were conducted for possible risk subjects and their parents. RESULTS:
      (1) The total score of the SJS-PSYA was correlated negatively with the total
      number of risk variables. (2) Eight out of 10 single risk variables were
      correlated with the total self-perception score. Better subjective health, higher
      aspiration for future, employed at present, much satisfaction in life, much
      support from friends as well as family and higher appraisal of nurturance of own
      parents, higher was the total self-perception score. These results suggest that
      the SJS-PSYA could be used in identifying young adults at risk and for
      intervention.

PMID- 11298202
TI  - Action research in action: reflections on a project to introduce Clinical
      Practice Facilitators to an acute hospital setting.
AB  - AIMS OF THE PAPER: The process and philosophical basis of action research are
      discussed in this article by reviewing the insights that were gained from a study
      designed to enhance the support available to junior nursing staff in an acute
      hospital setting. RATIONALE: It has been well documented that newly qualified
      nurses require help to develop professional competencies. With this in mind, the
      role of Clinical Practice Facilitator was established within a National Health
      Service (NHS) Trust to enhance clinical skill acquisition and the professional
      development of newly registered nurses and health care assistants. DESIGN: In
      order to facilitate the inception, development and subsequent evaluation of these
      new roles, an action research approach was adopted. Strategies used to encourage
      collaboration and flexibility during the project are also discussed. RESULTS: The
      primary aims of the project were achieved and the authors suggest that the choice
      of action research was significant to the successful outcome. However, a number
      of issues arose which deserve more attention including the importance of the
      interpersonal skills of the action researcher and the value of action research to
      facilitate change which is relevant at both an individual and organizational
      level.

PMID- 11298203
TI  - A literature review on the concept of intimacy in nursing.
AB  - AIM: This paper explores the concept of intimacy in nursing. RATIONALE: Intimacy
      is an increasingly important concept in nursing and feature of the nurse-patient
      relationship, which is perceived to be intrinsic to the proposed therapeutic
      potential of nursing. The introduction to the paper highlights the theoretical
      enthusiasm and endorsement of intimacy, the apparent lack of conceptual clarity
      from a nursing perspective and little published research investigating intimacy
      in practice. METHOD: Literature is reviewed from nursing and a variety of health
      related disciplines. FINDINGS: The paper traces the historical background of the
      nurse-patient relationship and intimacy and highlights the change in value from
      detachment and distancing to intimacy, commitment and involvement. The nature of
      intimacy is examined and a concept analysis based on literature from psychology
      and psychiatric medicine is critically analysed. Intimacy is suggested to have
      psychological, emotional and physical aspects, which are explored. An
      ethnographic research study on intimacy in nursing is reviewed, which also
      recognizes physical and emotional dimensions of the concept and the importance of
      sufficient resources to allow the close relationships advocated. Attention is
      drawn to the constraints on intimacy imposed by the current market-led health
      service. Literature and research on the implications and consequences of intimacy
      for the nurse are discussed. These report practical difficulties of maintaining
      close relationships with individual patients and the potential for over
      involvement and emotional labour. CONCLUSION: The paper concludes with the
      increasing importance attached to intimacy in nursing and its complex, ill
      defined nature. This serves to highlight the importance of research aimed at
      exploring and clarifying intimacy and further illustrating the therapeutic
      potential of nursing.

PMID- 11298204
TI  - Advancing the science of symptom management.
AB  - Since the publication of the original Symptom Management Model (Larson et al.
      1994), faculty and students at the University of California, San Francisco (UCSF)
      School of Nursing Centre for System Management have tested this model in research
      studies and expanded the model through collegial discussions and seminars. AIM:
      In this paper, we describe the evidence-based revised conceptual model, the three
      dimensions of the model, and the areas where further research is needed.
      BACKGROUND/RATIONALE: The experience of symptoms, minor to severe, prompts
      millions of patients to visit their healthcare providers each year. Symptoms not
      only create distress, but also disrupt social functioning. The management of
      symptoms and their resulting outcomes often become the responsibility of the
      patient and his or her family members. Healthcare providers have difficulty
      developing symptom management strategies that can be applied across acute and
      home-care settings because few models of symptom management have been tested
      empirically. To date, the majority of research on symptoms was directed toward
      studying a single symptom, such as pain or fatigue, or toward evaluating
      associated symptoms, such as depression and sleep disturbance. While this
      approach has advanced our understanding of some symptoms, we offer a generic
      symptom management model to provide direction for selecting clinical
      interventions, informing research, and bridging an array of symptoms associated
      with a variety of diseases and conditions. Finally, a broadly-based symptom
      management model allows the integration of science from other fields.

PMID- 11298205
TI  - Utility of health belief model as a guide for explaining or predicting breast
      cancer screening behaviours.
AB  - AIM: The purpose of this study was to assess the utility of HBM as a theoretical
      guide for predicting breast cancer screening and therefore for guiding
      intervention studies. BACKGROUND: Breast cancer is the leading cause of death for
      middle age women (35-50) and the second leading cause of cancer deaths in all
      women in the United States (US). Early detection of breast cancer through
      screening is the only option available to women. However, less than half of all
      women in the US participate in screening. The health belief model (HBM), which
      specifies interactions of values and beliefs about health and their influence on
      choices, has been widely used to explain screening behaviour. METHODS: An
      integrative research review analysed 16 published descriptive studies employing
      HBM. Literature was located through a search of research based studies listed in
      Cumulative Index of Nursing and Allied Health (CINAHL), Medline, and cancer
      literature databases and studies cited in other references between 1990 and 1999.
      FINDINGS: Application of HBM was inconsistent. No study tested nonlinear
      relationships between variables as specified in the model. At best, the model
      explained 47% of the variance in screening behaviour when socioeconomic status
      was included. Otherwise predictive power was low, ranging from 15 to 27%.
      CONCLUSIONS: While the model provides some description of the values, beliefs and
      behaviours of middle-aged women primarily, HBM does not appear to have the power
      to consistently predict behaviours. Further research is needed to provide more
      thorough depiction of the social, nonhealth care meaning of breast cancer.

PMID- 11298206
TI  - The parturient woman: can there be room for more than 'one person with full and
      equal rights inside a single human skin'?
AB  - AIMS OF THE PAPER: The aim of the paper is to raise awareness around the legal
      and ethical issues involved in the enforcement of caesarean sections on non
      consenting women. The paper considers the competing rights of mother and foetus
      in situations where a mother's wishes may result in harm or death to the foetus.
      BACKGROUND/RATIONALE: In this light of various court decisions about enforcing
      caesarean sections, the paper examines the pertinent legal and ethical issues,
      recognising that health professionals need to operate within an explicit legal
      and ethical framework. Content. The arguments about a woman's right to autonomous
      decision-making and a foetus' absolute right to life are examined with the focus
      throughout being on the legal framework. The need for health professionals to
      work within this as well as to avoid the temptation to base individual clinical
      decisions or professional behaviour on subjective moral judgements is emphasized.
      The attitudes of the judiciary are considered along with recent legal
      developments. There is an analysis of the way in which established legal
      principle is sometimes circumvented to override a woman's right to autonomy. The
      part played by lawyers and health professionals in denying a woman's competence
      to consent in order to achieve an outcome of which they approve is critically
      appraised. The basis for the decisions in these cases is deconstructed, along
      with a discussion of the role of health professionals in contributing to the
      dilemmas highlighted. CONCLUSION: It is essential that nurses or midwives caring
      for pregnant women have a full understanding of the legal and ethical issues
      surrounding this complicated and emotive area and where they, as health
      professionals, fit within this. The subject matter is also a useful arena for
      debating such ethical and legal issues as capacity and competence to consent as
      well as the extent of the right of any patient to full autonomy.

PMID- 11298208
TI  - Doctors' and nurses' perceptions of ethical problems in end-of-life decisions.
AB  - AIMS: To identify and compare doctors' and nurses' perceptions of ethical
      problems. Rationale. Ethical problems are a source of tension for health
      professionals. Misunderstandings or conflicts may result from differing
      perceptions of ethical problems. If true collaboration is to be achieved, it is
      important to understand the perspectives of others, particularly when difficult
      end-of-life decisions must be made. METHODS: In this qualitative study a total of
      seven doctors and 14 nurses working in acute care adult medical-surgical areas,
      including intensive care, were asked to describe ethical problems that they
      frequently encounter in practice. Interviews were taped and transcribed. Thematic
      analysis followed. RESULTS: All participants experienced ethical problems around
      decision making at the end of life. The core problem for both doctors and nurses
      was witnessing suffering, which engendered a moral obligation to reduce that
      suffering. Uncertainty about the best course of action for the patient and family
      was a source of moral distress. Competing values, hierarchical processes, scarce
      resources, and communication emerged as common themes. The key difference between
      the groups was that doctors are responsible for making decisions and nurses must
      live with these decisions. Each group, therefore, asked different questions when
      encountering and interpreting sources of moral distress. CONCLUSIONS: It was
      concluded that observed differences between doctors and nurses were a function of
      the professional role played by each rather than differences in ethical reasoning
      or moral motivation. Although this was a small qualitative study on one
      institution, and may not be generalizable, results suggest that doctors and
      nurses need to engage in moral discourse to understand and support the ethical
      burden carried by the other. Administrators should provide opportunities for
      discourse to help staff reduce moral distress and generate creative strategies
      for dealing with this.

PMID- 11298209
TI  - A descriptive study of meaning of illness in chronic renal disease.
AB  - AIM: To explore the subjective meaning of illness in a sample of renal patients.
      BACKGROUND: Patients' illness representations, such as the meaning they attach to
      illness, may affect their coping and adaptation. Improved understanding in this
      area may therefore benefit patient care. Meaning of illness has not previously
      been explored in renal disease. DESIGN AND METHODS: Cross-sectional survey
      (n=405) in a single regional renal unit in the North of England. Ethical approval
      was obtained and patients gave written consent. The instrument used was an eight
      item schema, based on the work of Lipowski (1970, Psychiatry in Medicine 1, 91
      102). Field notes regarding rationale for choice were recorded concurrently, then
      content analysed to enable identification of themes. The chi-square test
      (significance level P < 0.05) was used to analyse differences in selected meaning
      in older and younger patients; males and females; and patient groups
      (predialysis, haemodialysis and transplant). FINDINGS: 'Challenge' was selected
      by most patients (n=253, 62.5%), with similar results in all three patient
      groups. Slightly more older than younger patients selected 'challenge', although
      the difference was not statistically significant and older patients more commonly
      had a fatalistic interpretation of the option. More men selected 'challenge' than
      women. Those selecting 'challenge' and 'value' appeared to have a more positive
      outlook than other patients. CONCLUSIONS: Patients had identifiable meanings for
      their illness, and these may be associated with their response to renal disease.
      The schema appeared to be comprehensive, but is in need of further refinement.
      Consideration of the possible influence of social desirability is necessary.

PMID- 11298210
TI  - Why is pain management suboptimal on surgical wards?
AB  - BACKGROUND: During a patient's stay on a surgical ward, nurses hold a great deal
      of responsibility for pain management, especially when analgesics are prescribed
      on a PRN ('as needed') basis. Despite the availability of effective analgesics
      and new technologies for drug administration, studies continue to demonstrate
      suboptimal pain management. AIM OF THE STUDY: To identify perceived barriers to
      effective pain management in nursing practice. METHODS: The data are drawn from
      six nurse interviews and a survey of 180 nurses in 14 United Kingdom (UK)
      hospitals, which built upon detailed observations of nurses on surgical wards.
      RESULTS: In a question about possible reasons for suboptimal pain management,
      nurses identified a number of barriers that concerned organizational aspects such
      as workload and lack of staff, and also legal or institutional constraints.
      Nurses further stated that analgesic prescribing was sometimes inadequate, or
      that doctors or the pain team were unavailable to review medication. Further
      barriers that nurses may be less aware of were identified in a question
      concerning nurses' reasons for not asking patients a pain-related question during
      drug rounds. Previous observations had shown this to be the predominant time for
      pain questioning. The most commonly mentioned reasons were that patients were
      asleep, on epidural or patient controlled analgesia (PCA), or had recently had an
      analgesic. Nurses' replies also revealed that they relied considerably on
      patients' nonverbal behaviour and used this to assess analgesia requirements.
      Nurses' views and judgements regarding pain management were further supported in
      replies to a number of attitude statements and a question about the aim of
      administering analgesia. CONCLUSION: The strength of this work is that it
      identified two types of potential barriers to effective pain management,
      recognized and more subconscious ones, and both need to be addressed before
      introducing systems aimed at improving pain management.

PMID- 11298211
TI  - A need to try everything: patient participation in phase I trials.
AB  - RATIONALE: The area of phase I trials is fraught with ethical dilemmas and
      controversy. Most existing research focuses on issues of human rights and the
      informed consent procedure. Little attention has been given to patients'
      perceptions of participating in such trials. DESIGN: This paper describes a study
      using qualitative interviews and open-stem questionnaires to begin to explore
      patients' own perceptions of any benefits from participating in phase I trials.
      RESULTS: Findings suggest that for some patients, phase I trials fulfil a need to
      try everything in their fight against cancer. The study also suggests that being
      on treatment allows some patients to construct their lives meaningfully by
      providing a supportive structure and enabling hope. Implications for nursing
      practice and further research are discussed.

PMID- 11298212
TI  - Video modelling to educate patients.
AB  - BACKGROUND: Changes in health care delivery in the United States of America due
      to economic pressures have required nurses to develop innovative instructional
      materials for educating patients and families. Educational materials such as
      videotapes, specifically designed to provide information and promote active
      participation in treatment decisions, can be effective tools for empowering
      patients. A comprehensive analysis in 1988 concluded that the concept of 'video
      modelling' or 'behavioural modelling' offered the greatest benefit of videotaped
      presentations. AIM OF THE STUDY: The purpose of this integrative literature
      review was to examine the concept of video modelling and its applications in
      clinical practice. METHODS: A computer search of the electronic databases of
      Medline and CINHAL between 1990 and 1999 produced a total of 40 research studies
      on video instruction for patients. Based on criteria for inclusion, 18 research
      studies involving video modelling were reviewed and three major uses were
      identified: (1) assisting decision making regarding treatment options; (2)
      reducing pre-procedural anxiety and improving coping skills; and (3) teaching
      self-care practices. RESULTS: The studies reviewed included a variety of research
      designs, clinical settings, and patient populations. Despite these differences,
      several benefits to the use of video modelling were found. Patients who viewed
      videotapes regarding treatment options had a greater understanding of the risks
      and benefits of those choices and were more apt to be active participants in
      decision making. Collective results of the studies focusing on stress and coping
      revealed that preparatory videotapes using video modelling could have a positive
      effect on reducing anxiety and physiological arousal during stressful procedures.
      With self-care practices, several of the studies found that there was an increase
      in desired behaviours in people whose educational programmes included video
      modelling. CONCLUSIONS: The use of video modelling has potential benefits for
      clinical practice in facilitating knowledge acquisition, reducing preparatory
      anxiety, and improving self-care. Nurses must become more actively involved in
      evaluating various teaching approaches used with patients to enhance practice and
      outcomes.

PMID- 11298213
TI  - Persons with insulin-dependent diabetes mellitus: acceptance and coping ability.
AB  - AIMS: The purposes of this study were to describe how persons with insulin
      dependent diabetes mellitus (IDDM) accept their disease and what sense of
      coherence they have, in order to determine whether a person's acceptance of the
      disease is related to his or her sense of coherence. Whether acceptance of the
      disease and sense of coherence are related to the disease duration, complications
      of the disease, metabolic control and demographic data would also be determined.
      DESIGN: One hundred and seven, randomly selected, insulin-dependent, diabetic
      subjects (47 men and 60 women) participated in the study. The Acceptance of
      Disability Scale Modified (ADM scale), the Sense of Coherence Scale (SOC scale),
      a study-specific questionnaire and the patients records were used to collect the
      data. BACKGROUND: IDDM implies a major change in way of life. Ingrained
      procedures and patterns of behaviour must be adapted to the disease and its
      treatment. RESULTS: The results of the present study show that educational level
      seems to be an important factor for how well a person accepts the disease and the
      sense of coherence. Persons with higher scores on the ADM and the SOC scales had
      higher levels of education. Moreover, they also had a better metabolic control.
      Individuals with a poor metabolic control had more disease-related complications.
      A significant correlation between the ADM and the SOC scores was found,
      indicating that persons with a high degree of acceptance of the IDDM also had a
      high coping capability. CONCLUSIONS: It is important to individualize the care of
      subjects with IDDM and to identify the persons with low acceptance of their
      disease and a low sense of coherence.

PMID- 11298214
TI  - Hope, despair and hopelessness in living with HIV/AIDS: a grounded theory study.
AB  - BACKGROUND: Hope, despair or hopelessness have been detected in several research
      reports as important elements of the lives of persons living with human
      immunodeficiency virus (HIV) (PLWH) or acquired immunodeficiency syndrome (AIDS)
      (PLWA). However, there is an obvious gap in the literature suggesting a need to
      study the overall dynamics of hope (including both hope and despair or
      hopelessness) along the HIV spectrum from PLWHs' and PLWAs' perspective. AIM: The
      purpose of this study was to describe the dynamics of hope in living with
      HIV/AIDS. METHODS: The data were collected through interviewing 10 PLWHs/PLWAs
      and analysed using a grounded theory method. FINDINGS: The dynamics of hope is a
      multifaceted and complex combination of 'hope', 'despair' and 'hopelessness'. It
      comprises balancing between 'believing life to be worth living at the present and
      in the future', 'losing one's grip and sinking into narrowing existence vs.
      fighting against sinking' and 'giving up in the face of belief in nonexisting
      future'. A dynamic alternation between hope, despair and hopelessness takes place
      in the presence of factors that contribute to the 'folding' and 'unfolding'
      possibilities in everyday life. Factors contributing to the folding possibilities
      include 'losing', 'fear', 'uncertainty', 'problems in care', 'HIV/AIDS in close
      ones', 'difficulties in relationships' and 'negative public images and attitudes
      concerning HIV'. Factors contributing to the unfolding possibilities are
      'constructive life experiences', 'wishing not to have HIV while uncertain',
      'constructive relationships', 'ability to control one's life', 'finding the
      meaning of life and zest for life', 'caring', 'noticing one's improved health and
      the continuance of life', 'increasingly positive attitudes concerning HIV
      positive people' and 'protection by law'. CONCLUSIONS: The dynamics of hope
      discovered in this study present new conceptualization, where hope, despair and
      hopelessness are viewed in relation to each other. The emerged definitions may be
      used in clinical practice to identify these phenomena in individuals with
      HIV/AIDS. The discovered factors contributing to the folding and unfolding
      possibilities can be used in clinical practice to help the individuals along the
      dynamics of hope.

PMID- 11298215
TI  - Spirituality and psychosocial factors in persons living with HIV.
AB  - AIM OF THE STUDY: This pilot study was designed to examine the relationships
      among spirituality and psychosocial factors in a sample of 52 adult males living
      with human immunodeficiency virus (HIV) disease and to determine the most
      reliable spirituality measure for a proposed longitudinal study. BACKGROUND: HIV
      disease is among the most devastating of illnesses, having multiple and profound
      effects upon all aspects of the biopsychosocial and spiritual being. Although
      research has suggested relationships among various psychosocial and spiritual
      factors, symptomatology and physical health, much more research is needed to
      document their potential influences on immune function, as well as health status,
      disease progression, and quality of life among persons with HIV disease. METHODS:
      This descriptive correlational study explored the relationships of spirituality
      and psychosocial measures. Spirituality was measured in terms of spiritual
      perspective, well-being and health using three tools: the Spiritual Perspective
      Scale, the Spiritual Well-Being Scale, and the Spiritual Health Inventory. Five
      psychosocial instruments were used to measure aspects of stress and coping: the
      Mishel Uncertainty in Illness Scale, Dealing with Illness Scale, Social
      Provisions Scale, Impact of Events Scale, and Functional Assessment of HIV
      Infection Scale. The sample was recruited as part of an ongoing funded study. The
      procedures from the larger study were well-defined and followed in this pilot
      study. Correlational analyses were done to determine the relationship between
      spirituality and the psychosocial measures. FINDINGS: The findings indicate that
      spirituality as measured by the existential well-being (EWB) subscale of the
      Spiritual Well-Being Scale was positively related to quality of life, social
      support, effective coping strategies and negatively related to perceived stress,
      uncertainty, psychological distress and emotional-focused coping. The other
      spirituality measures had less significant or non significant relationships with
      the psychological measures. CONCLUSIONS: The study findings support the inclusion
      of spirituality as a variable for consideration when examining the psychosocial
      factors and the quality of life of persons living with HIV disease. The spiritual
      measure that best captures these relationships is the EWB subscale of the
      Spiritual Well-Being Scale.

PMID- 11298216
TI  - Accounting for overlap? An application of Mezzich's kappa statistic to test
      interrater reliability of interview data on parental accident and emergency
      attendance.
AB  - STUDY RATIONALE: The number of interview studies with service users is rising
      because of growth in health services research. The level of agreement between
      multiple interview data coders requires statistical calculation to support
      results. Basic kappa statistics are often used but this depends on having
      mutually exclusive data. Researchers should be aware that this is not valid when
      an interview word or paragraph can be coded into more than one category. The
      'proportional overlap' kappa extension by Mezzich et al. (1981, Journal of
      Psychiatric Research 16, 29-39) has been investigated as an original solution.
      OBJECTIVES: To assess the level of agreement beyond chance between several raters
      of interview data by applying the 'proportional overlap' kappa statistic by
      Mezzich et al. to verbal interview data. The clinical area investigated was child
      attendance at an Accident and Emergency Department, where parental attendance
      experiences have been under-explored. METHODS: Two researchers using a coding
      schedule coded a random sample of interview transcripts. These data were applied
      to Mezzich's procedure; coder 1 notes that a paragraph refers to category A and B
      but coder 2 notes A, B and C. The total agreement overlap in this case was 0.66
      because two actual agreements out of three possible agreements were made. This
      was repeated for each paragraph and divided by the number of coding pairs. All
      agreement values were summed then subsequently divided by the total number of
      paragraphs to get Po (total number of observed agreements) and by the total
      number of coding pairs to get Pe (total number of agreements by chance alone). Po
      and Pe were used in the basic kappa formula to assess interview coding
      reliability. RESULTS: The overall mean Po was 0.61, the mean Pe was 0.32, with a
      kappa score of 0.43; a moderate level of agreement which was statistically
      significant (t=4.8, P < 0.001, d.f.=23). CONCLUSION: Mezzich's procedure may be
      applied to interview data to calculate agreement levels between several coders.

PMID- 11298217
TI  - From individual to group: use of narratives in a participatory research process.
AB  - AIMS: This paper provides a theoretical understanding of narrative research and
      its use in research. It aims to expose the ways narrative research, when taken
      beyond the researcher's lone analysis of text, can contribute to the development
      of clinical knowledge. BACKGROUND: Methodological approaches involving the
      construction of narratives are increasingly apparent in the nursing and allied
      health literature. Narratives, constructed from stories of nursing practice,
      become texts available for analysis. This is undertaken predominantly by a
      researcher engaged in a lone activity with little involvement of those
      contributing the stories. METHODS: This paper is drawn from a critical praxis
      study of nurse-patient friendship utilizing participatory research processes. The
      nurses involved in the study were co-researchers in an indepth study of their
      relationships with patients. FINDINGS: The paper traces the movement from naive
      story, through individual narratives during interviews with each nursing and
      demonstrates the changes in understanding about the narrative accounts that
      occurred during the participatory group process. CONCLUSION: The nurses involved
      in this study were able, through the use of narrative stories reexamined in a
      group context, to develop new insights and understandings about their practice.
      Knowledge generated in these ways remains grounded in the real life world of
      clinical nursing and gives voice to the complexity of those aspects of nursing
      practice that are taken for granted.

PMID- 11298218
TI  - Focus groups as a research method: a critique of some aspects of their use in
      nursing research.
AB  - OBJECTIVE: To evaluate and critique reports in the nursing literature in the
      period 1990-1999 of the use of focus groups as a research method. METHODS: The
      articles were identified by a computerized search of the CINAHL database and
      subjected to critical review. FINDINGS: The result of the search was that very
      few articles were found that reported on a specific piece of research using the
      method. Methodological discussions were more common and these were sometimes at a
      somewhat superficial level without analysis or critique. The largest category of
      articles was concerned with service development projects. The research-based
      articles were found to be relatively unsophisticated in their use of the method,
      in particular in relation to data analysis and social interaction within focus
      groups. Terms such as 'content analysis' and 'grounded theory' were used in
      nonrigorous ways and incompatibility between the underlying research approach and
      implementation of the method was identified in the cases of phenomenology and
      grounded theory. Whilst selection of the focus group method was often justified
      in terms of the benefits that participant interaction could yield, this
      interaction was rarely reported or discussed in the articles. One author proposed
      a scheme for analysing this type of interaction, and this is recommended to
      future researchers as a possible framework for interaction analysis. CONCLUSIONS:
      The article concludes by calling for more in-depth consideration at the research
      planning stages of the underlying assumptions of methodological approaches that
      may be used to underpin focus group research and methods to be used to analyse
      and report the data generated.

PMID- 11298219
TI  - A method to develop a nursing intervention: the contribution of qualitative
      studies to the process.
AB  - AIM OF THE PAPER: To describe how to develop a patient-centred nursing
      intervention (NI). BACKGROUND: The stimulus for scrutinizing methods and
      techniques to develop a NI was a research project concerning the contribution of
      information and support to the sexual adaptation of women with gynaecological
      cancer. Within this project, a NI for sexual teaching (ST) was developed because
      the literature review revealed no tested NI for this purpose. How patients
      experience and perceive received information influences the usefulness and
      efficacy of a teaching intervention. Qualitative methods provide insight and
      understanding of patients' experience. Consequently, qualitative methods are
      appropriate to use when developing interventions that aim to influence patients'
      situations through the provision of information. METHOD: Previously reported
      approaches for developing an intervention did not match the goals and underlying
      premises identified for the intervention under development. An alternative
      method, consisting of a design phase and a testing phase, was developed. The goal
      of the design phase was to develop a working definition of the intervention and
      to formulate recommendations for carrying out the intervention. Written
      guidelines provided concrete examples of the topics to discuss and how to discuss
      them. During the design phase, a qualitative study was conducted to describe the
      lived-experience of the phenomenon that the information should influence, namely
      sexuality after treatment for gynaecological cancer. In the testing phase, a
      different type of qualitative study took place. The patients' experience of
      receiving information and the nurses' experience of providing it were
      investigated in order to refine the proposed intervention, to identify the
      results patients hope to achieve (or achieved) and to explore the underlying
      theoretical explanation of the intervention. During the testing phase, the
      feasibility and acceptability of the modified intervention were both established.
      CONCLUSION: Even when the starting point is advice from care-givers, an
      intervention can be developed that is in harmony with the patient perspective
      when qualitative studies are part of the process.

PMID- 11298220
TI  - The conceptual structure of physical touch in caring.
AB  - AIMS OF THE STUDY: This study was conducted to clarify and to conceptualize the
      phenomena of physical touch in caring. BACKGROUND: Physical touch occurs
      frequently in patient care situations and has specific meanings within the
      context of caring. However, the concept of physical touch in caring has not been
      well articulated in the literatures, although the phenomena of touch and physical
      touch have been studied in relation to comfort, sense of well-being and
      connectedness. DESIGN/METHOD: The Hybrid Model of concept development was applied
      to develop a conceptual structure of physical touch in caring, which included a
      field study carried out in Seoul, South Korea using in-depth interviews with 39
      adult subjects consisting of health-care professionals, in-patients, and healthy
      persons. RESULTS/FINDINGS: The concept of physical touch in caring emerged as a
      complex phenomenon having meanings on several different dimensions which were
      encompassed several attributes and the conceptual structure of physical touch in
      caring centred around five aspects of goals for physical touch: promoting
      physical comfort, promoting emotional comfort, promoting mind-body comfort,
      performing social role, and sharing spirituality. CONCLUSIONS: Physical touch in
      caring as a concept having the dimensions of physical, emotional, social, and
      spiritual significance needs to be treated in a holistic way and it is possible
      to enrich the meanings and methods of physical touch in nursing so that its
      application may have effects that have positive impacts on patients' well-being
      and comfort.

PMID- 11298221
TI  - Examining the process of community development.
AB  - AIM OF THE STUDY: To present the results of evaluation research investigating a
      successful community development project. RATIONALE: Many governments, health
      care agencies, and organizations require community participation in health care.
      As a result, nurses and other health professionals are often required to practice
      using a philosophy of community development. Although the theoretical,
      philosophical, and practical components of community development are well
      articulated, there is little evidence that exemplifies the experience of
      initiating and participating in a community development project. This paper
      provides evidence of how one organization successfully engaged the broader
      community on a respite care project. METHOD: Using qualitative research methods
      and guided by the principles and practices of participatory action research, this
      evaluation engaged with the community in data collection, analysis, dissemination
      of finding, and in promoting effective change. RESULTS: Four themes emerged that
      provide insight into how one HIV/AIDS organization successfully undertook
      community development. These themes include: (a) identifying a community need;
      (b) addressing the various components identified in the community development
      process; (c) highlighting the strategies used to engage in successful community
      development; and (d) attending to factors that influence community development.
      CONCLUSION: The results of this research contribute to the body of knowledge
      related to engaging in the process of community development. By highlighting the
      experiences of one community group, it is hoped that nurses can learn and
      incorporate this knowledge into practice.

PMID- 11298223
TI  - Induction, growth and antibiotic production of Streptomyces viridifaciens L-form
      bacteria.
AB  - AIMS: To induce, cultivate and investigate the characteristics of L-form bacteria
      derived from the filamentous actinomycete Streptomyces viridifaciens. METHODS AND
      RESULTS: L-forms were induced in a liquid medium supplemented with lysozyme and
      penicillin. A stable culture which no longer required inducing agents but could
      still revert, was obtained by the twelfth subculture. The specific growth rate of
      stable L-forms was faster (0.751) than unstable L-forms (0.361). After the
      exponential growth phase, the cell diameter continued to increase, as did the
      percentage of vacuoles. Morphologically, the L-forms appeared as spherical bodies
      with no signs of differentiation and were sensitive to osmotic stress, indicating
      removal of the cell wall. The L-forms produced secondary metabolites although
      much lower levels of antibiotic were assayed in the L-forms compared with the
      cell walled forms. CONCLUSION: Stable L-form bacteria were induced from S.
      viridifaciens and their growth characterized. The L-forms produced secondary
      metabolites. SIGNIFICANCE AND IMPACT OF THE STUDY: Stable Streptomyces L-forms
      were induced and have potential as biocontrol agents.

PMID- 11298222
TI  - Examining the effects that manipulating information given in the change of shift
      report has on nurses' care planning ability.
AB  - AIM OF THE STUDY: To investigate the effect that manipulating the style and
      content of the nurse change of shift report had on an individual's ability to
      plan patient care. BACKGROUND: The nurse change of shift report occurs on most
      hospital wards at least two if not three times a day. However, little research
      exists examining how changing the style and information content of the shift
      report may affect an individual's ability to process the information they hear.
      It is suggested that how individuals structure their knowledge, in the form of
      schema, is an important consideration when examining how they process
      information. DESIGN: This was an experimental study where two independent
      variables, report style (retrospective vs. prospective) and schema information
      (schema consistent vs. schema inconsistent) were compared in a factorial design.
      A convenience sample of 48 registered nurses from acute medical and acute
      surgical wards were randomly allocated to one of the four experimental
      conditions. Outcome measures included the amount of information that subjects
      accurately recorded and recalled from the shift report, together with their
      ability to plan patient care. RESULTS: Results indicated that the type of report
      had a significant effect on an individual's ability to plan patient care, and
      type of information content on their ability to accurately record and recall the
      information they heard. CONCLUSIONS: The implications of the results, both for
      schema theory as an explanation of nursing knowledge, and for the type of report
      which should be used in acute medical and acute surgical wards are discussed,
      together with the implications of the study for further research.

PMID- 11298224
TI  - RAPD-PCR typing of Acinetobacter isolates from activated sludge systems designed
      to remove phosphorus microbiologically.
AB  - AIMS: This study investigated whether there were differences in RAPD fingerprints
      between already described genomic species of Acinetobacter and those from
      activated sludge systems. Whether plant-specific populations of acinetobacters
      exist was also examined. METHODS AND RESULTS: Fifty-two isolates of Acinetobacter
      from four biological phosphorus removal (EBPR) systems of different
      configurations, and the known genomic species, were characterized using RAPD-PCR,
      and fragments separated on agarose gels. Patterns were analysed using Gel Pro
      software and data analysed numerically. RAPD-PCR produced patterns suggesting
      that many environmental isolates differ from known genomic species. In two cases,
      strains from individual plants clustered closely enough together to imply that
      there may be plant-specific populations of acinetobacters. CONCLUSION: The data
      suggest that current understanding of the taxonomic status of Acinetobacter may
      need modifying to accommodate non-clinical isolates, as many of the clusters
      emerging after numerical analysis of RAPD-PCR fragments from activated sludge
      isolates were quite separate from the clusters containing the already described
      genomic species. Some evidence was also obtained from the clusters generated to
      support a view that particular populations of Acinetobacter may occur in
      individual activated sludge plants. SIGNIFICANCE AND IMPACT OF THE STUDY: These
      data suggest that the current understanding of the systematics of Acinetobacter,
      based as it is almost exclusively on clinical isolates, may need drastic revision
      to accommodate environmental strains. They also suggest that a re-examination of
      the importance and role of Acinetobacter in the activated sludge process may be
      appropriate.

PMID- 11298225
TI  - Purification and characterization of an extracellular alpha-glucosidase protein
      from Trichoderma viride which degrades a phytotoxin associated with sheath blight
      disease in rice.
AB  - AIMS: To purify and characterize an extracellular alpha-glucosidase from
      Trichoderma viride capable of inactivating a host-specific phytotoxin, designated
      RS toxin, produced by the rice sheath blight pathogen, Rhizoctonia solani Kuhn.
      METHODS AND RESULTS: The host-specific RS toxin was purified from both culture
      filtrates (culture filtrate toxin, CFTox) and R. solani-inoculated rice sheaths
      (sheath blight toxin, SBTox). Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis analyses of extracellular proteins, purified from a biocontrol
      fungus T. viride (TvMNT7) grown on SBTox and CFTox separately, were carried out.
      The antifungal activity of the purified high molecular weight protein (110 kDa)
      was studied against RS toxin as well as on the sclerotial germination and
      mycelial growth of R. solani. Enzyme assay and Western blot analysis with the
      antirabbit TvMNT7 110-kDa protein indicated that the protein was an alpha
      glucosidase. The 110-kDa protein was highly specific to RS toxin and its
      Michaelis-Menten constant value was 0.40 mmol l-1 when p-nitrophenyl alpha-D
      glucopyranoside was used as the substrate. The isoelectric point of the protein
      was 5.2. N-terminal sequencing of the alpha-glucosidase protein showed that its
      amino acid sequence showed no homology with other known alpha-glucosidases.
      CONCLUSION: This appears to be the first report of the purification and
      characterization of an alpha-glucosidase capable of inactivating a host-specific
      toxin of fungal origin. The alpha-glucosidase is specific to RS toxin and is
      different from the known alpha-glucosidases. SIGNIFICANCE AND IMPACT OF THE
      STUDY: As RS toxin could be inactivated by the microbial alpha-glucosidase
      enzyme, isolation of the gene that codes for the enzyme from T. viride and
      transfer of the gene to rice plants would lead to enhanced resistance against
      sheath blight pathogen by inactivation of RS toxin.

PMID- 11298227
TI  - Metabolic response of biofilm to shear stress in fixed-film culture.
AB  - AIMS: In a biofilm reactor, detachment force resulting from hydraulic shear is a
      major factor that determines the formation and structure of steady state biofilm.
      The metabolic response of biofilm to change in shear stress was therefore
      investigated. METHODS AND RESULTS: A conventional annular reactor made of PVC was
      used, in which shearing over the rotating disc surface was strictly defined.
      Results from the steady state aerobic biofilm reactor showed that the biofilm
      structure (density and thickness) and metabolic behaviour (growth yield and
      dehydrogenase activity) were closely related to the shear stress exerted on the
      biofilm. Smooth, dense and stable biofilm formed at relatively high shear stress.
      Higher dehydrogenase activity and lower growth yield were obtained when the shear
      stress was raised. Growth yield was inversely correlated with the catabolic
      activity of biofilm. The reduced growth yield, together with the enhanced
      catabolic activity, suggests that a dissociation of catabolism from anabolism
      would occur at high shear stress. CONCLUSION: Biofilms may respond to shear
      stress by regulating metabolic pathways associated with the substrate flux
      flowing between catabolism and anabolism. A biological phenomenon, besides a
      simple physical effect, is underlying the observed relation between the shear
      stress and resulting biofilm structure. SIGNIFICANCE AND IMPACT OF THE STUDY: A
      hypothesis is proposed that the shear-induced energy spilling would be associated
      with a stimulated proton translocation across the cell membrane, which favours
      formation of a stronger biofilm. This research may provide a basis for
      experimental data on biofilm obtained at different shear stresses to be
      interpreted in relation to energy.

PMID- 11298226
TI  - Phage-displayed peptides that mimic aflatoxin B1 in serological reactivity.
AB  - AIMS: To test phage-displayed random peptide libraries as sources of peptides
      that mimic the binding of aflatoxin B1 to monoclonal antibodies raised against
      the toxin. METHODS AND RESULTS: For two of the three MAbs tested, clones were
      obtained by panning, producing phage that bound specifically to MAb 13D1-1D9 (MAb
      24; specific for aflatoxins B1 and G1) and MAb 6E12-1E9 (MAb 13; specific for
      aflatoxins B1, G1 and B2) in ELISA. The amino acid sequences of the binding
      peptides varied. Those binding to MAb 24 contained the sequence of '...YMD...',
      and those that bound to MAb 13 contained the dipeptide 'PW'. Mimotope phage was
      used in a competition ELISA format for assaying aflatoxin concentrations.
      CONCLUSION: The results show that mimotope preparations are effective substitutes
      for pure toxin in these ELISA procedures. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These results should contribute significantly to enhancing the safety and
      diminishing the costs of aflatoxin assays.

PMID- 11298228
TI  - Establishment of orally-administered Lactobacillus gasseri SBT2055SR in the
      gastrointestinal tract of humans and its influence on intestinal microflora and
      metabolism.
AB  - AIMS: To investigate the fate of a streptomycin-rifampicin-resistant variant of
      Lactobacillus gasseri SBT2055 (LG2055SR) and the influence of its oral
      administration on the composition and metabolism of the intestinal microflora.
      METHODS AND RESULTS: Intestinal passage of LG2055SR was monitored by a
      combination of selection with antibiotics and identification by a randomly
      amplified polymorphic DNA (RAPD)-PCR METHOD: Composition of intestinal microflora
      was analysed by the method developed by Mitsuoka et al. (1965, 1974).
      Establishment of orally-administered LG2055SR in the human intestine was
      confirmed in this study. LG2055SR ingestion specifically lowered faecal
      populations of Staphylococcus and faecal contents of p-cresol. CONCLUSION:
      LG2055SR and its parent strain, LG2055, are considered to be appropriate
      candidates for probiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: It is clarified
      that LG2055SR has the ability to establish in the human gastrointestinal tract
      and alters the composition and metabolism of the intestinal microflora and
      physical characteristics of faeces.

PMID- 11298229
TI  - Biosynthesis of PHB tercopolymer by Bacillus cereus UW85.
AB  - AIMS: The study was attempted to determine the ability of a Gram-positive
      Bacillus cereus UW85 strain to biosynthesize poly (3-hydroxybutyrate) copolymers
      when epsilon-caprolactone, or epsilon-caprolactone and glucose, were used as
      carbon sources. METHODS AND RESULTS: Bacillus cereus was grown for 24 h under
      nitrogen-limited conditions in a mineral salts medium. Growth was monitored by
      measurement of turbidity. Glucose level was determined by the colorimetric
      anthrone METHOD: The epsilon-caprolactone concentration was determined by gas
      chromatography. The bacterial biopolymers were extracted with chloroform in a
      Soxhlet extractor and then characterized by nuclear magnetic resonance and gel
      permeation chromatography. When epsilon-caprolactone was used as a carbon
      substrate, the bacterial strain produced tercopolymer with 3-hydroxybutyrate, 3
      hydroxyvalerate and 6-hydroxyhexanoate units. However, when caprolactone and
      glucose were supplied together, only homopolymer of poly (3-hydroxybutyrate) was
      produced. CONCLUSION: All tercopolymers isolated from B. cereus UW85 cells were
      obtained with yields up to 9% (w/w) and low number-average molecular weight
      compared with the homopolymer PHB. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus
      cereus UW85 produced tercopolymer with a low molecular weight from one substrate
      (epsilon-caprolactone) used as a carbon source. The results are significant for
      the potential future application of Bacillus biopolymers to bioplastics
      production.

PMID- 11298231
TI  - Identification by 16S-23S rDNA intergenic region amplification, genotypic and
      phenotypic clustering of Staphylococcus xylosus strains from dry sausages.
AB  - AIMS: To ascertain the identification and typing of the Gram-positive, coagulase
      negative cocci present in 'Salsiccia Sotto Sugna', an Italian artisanal sausage.
      METHODS AND RESULTS: Fifty-one strains were isolated and genotypically identified
      by amplification of the 16S-23S rDNA intergenic region with universal primers.
      Most isolates were identified as Staphylococcus xylosus and one strain as Staph.
      condimenti. Isolates were clustered by numerical analysis of both RAPD (Random
      Amplified Polymorphic DNA) PCR profiles and physiological characters. Genotypic
      clustering allowed the separation of strains showing nitrate reduction and amino
      acid decarboxylase activities. Phenotypic clustering distinguished strains
      isolated at diverse ripening stages. CONCLUSION: The predominance of Staph.
      xylosus in Italian dry sausages was confirmed. Genotypic similarities related to
      the possession of single phenotypic traits. SIGNIFICANCE AND IMPACT OF THE STUDY:
      In this study, a rapid method of Staphylococcus and Kocuria species distinction
      was proposed. The suitability of RAPD PCR to discriminate strains of Staph.
      xylosus with technologically relevant activities was reported.

PMID- 11298230
TI  - Recognition of Yersinia enterocolitica multiple strain infection in twin infants
      using PCR-based DNA fingerprinting.
AB  - AIMS: Yersinia enterocolitica causes several syndromes in humans. The most common
      presentation is enterocolitis in children, presenting as fever and diarrhoea. A
      Y. enterocolitica multiple strain infection in twin infants was investigated.
      METHODS AND RESULTS: One isolate was recovered from one patient and two
      morphologically-different isolates were recovered from the other infant.
      Biochemically, all isolates were identified as Y. enterocolitica group. The
      genomic DNA from each strain was purified and DNA fingerprinting was performed.
      The banding patterns observed for Y. enterocolitica isolates 2 and 3, from
      patients 1 and 2, respectively, were identical when comparing the presence or
      absence of major bands. However, Y. enterocolitica isolate 1, from patient 1,
      showed a distinctive banding pattern from isolates 2 and 3. CONCLUSION: The
      findings indicate that one infant was colonized by more than one strain of Y.
      enterocolitica, demonstrating that multiple strains can colonize and invade a
      patient. SIGNIFICANCE AND IMPACT OF THE STUDY: Recognition of multiple strain
      infections can be important in diagnosis, treatment and prognosis of Y.
      enterocolitica infections, as well as in disease epidemiology. The technique
      described here offers a straightforward method for strain comparison.

PMID- 11298232
TI  - Production of brown tyrosine pigments by the yeast Yarrowia lipolytica.
AB  - AIMS: To study the mechanism of production of brown pigments from tyrosine in the
      yeast Yarrowia lipolytica. METHODS AND RESULTS: Pigment formation was followed
      during growth in tyrosine medium, and the presence of the pigment precursor in
      the medium was assessed by evaluating pigment formation after removing the cells
      at different times of incubation. It was observed that the pigment precursor
      accumulated outside the cells during the exponential phase of growth, but pigment
      formation only occurred during the stationary phase of growth and resulted from
      the oxidation of the precursor. Pigment formation was repressed by glucose and L
      glutamine, and promoted by lactic acid, L-asparagine and glycine. Spectra of 1H
      and 13C-NMR revealed that the brown pigment was derived from tyrosine and was a
      polymer composed of a core of aromatic residues. CONCLUSION: The results indicate
      that pigments result from the extracellular accumulation and auto-oxidation of an
      intermediate of tyrosine catabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      is the first report on the mechanism of pigment production from tyrosine in a
      yeast species.

PMID- 11298233
TI  - A study into the role of L-aspartic acid on the metabolism of L-malic acid and D
      glucose by Oenococcus oeni.
AB  - AIMS: The purpose of this work was to study the effect of L-aspartic acid
      concentration on bacterial growth, D-glucose fermentation and L-malic acid
      consumption of Oenococcus oeni NCFB 1707. METHODS AND RESULTS: Bacterial cultures
      were performed in synthetic media. Bacterial growth, D-glucose fermentation and L
      malic acid consumption were reduced when L-aspartic acid concentration became
      excessive. This inhibitory effect of high concentrations of L-aspartic acid on
      bacterial growth was also observed with several Oenococcus oeni strains, except
      O. oeni BL01. The L-aspartic acid inhibitory effect on bacterial growth could be
      reduced by increasing the concentration of L-glutamic acid. L-glutamic acid
      transport was found to be competitively inhibited by L-aspartic acid. In
      addition, an excessive amount of L-aspartic acid modified D-glucose metabolism,
      with an overproduction of acetic acid and reduced ethanol production. CONCLUSION:
      Since L-glutamic acid is an essential amino acid for the bacterial strain used,
      the L-aspartic acid inhibitory effect on bacterial growth could be linked to its
      involvement in an antagonistic interaction with L-glutamic acid. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Such antagonistic interactions between amino acids in O.
      oeni strains could be another explanation for the difficulties of inducing
      malolactic fermentation in wines.

PMID- 11298235
TI  - Optimization of the wheat puroindoline-a production in Pichia pastoris.
AB  - AIMS: A recombinant puroindoline-a (rPIN-a) was produced using the methylotrophic
      yeast Pichia pastoris. METHODS AND RESULTS: In fed-batch culture, the production
      of rPIN-a decreased after 24 h of methanol induction. Most of the rPIN-a was not
      soluble in the culture medium remaining bound to the cell walls. Soluble and
      membrane-bound rPIN-a were quantified by ELISA after Triton X-114 phase
      partitioning. In order to improve the production of rPIN-a, the influence of pH,
      specific growth rate and the addition of TX-114 was tested on two independent
      continuous cultures. The production of rPIN-a was improved when continuous
      culture was carried out at 29 degrees C under acid conditions (pH 5) with a low
      dilution rate (D=0.025 h(-1)). The addition of 0.01% TX-114 to the medium
      inverted the ratio between the secreted and the membrane-bound rPIN-a.
      CONCLUSION: When a continuous culture was carried out under optimized conditions,
      the rPIN-a production yield was increased 10-fold to 14 mg l(-1) and 80% of the
      rPIN-a was soluble. SIGNIFICANCE AND IMPACT OF THE STUDY: This study would be
      helpful to optimize the expression of other membrane-bound proteins in P.
      pastoris.

PMID- 11298234
TI  - Expression of a modified Neocallimastix patriciarum xylanase in Butyrivibrio
      fibrisolvens digests more fibre but cannot effectively compete with highly
      fibrolytic bacteria in the rumen.
AB  - AIMS: This study investigated the competitive abilities of two Neocallimastix
      patriciarum-derived xylanases constructs in Butyrivibrio fibrisolvens H17c (xynA
      and pUMSX) and their ability to compete in vivo. METHODS AND RESULTS: The
      digestibility of neutral detergent fibre (NDF) increased during co-culture of
      xynA or pUMSX and weakly cellulolytic, but not with highly cellulolytic,
      ruminococci. Competition studies among xynA, pUMSX and cellulolytic consortia
      demonstrated that xynA was the fittest. XynA did not persist at high levels in
      the rumen and was undetectable after 22 days. CONCLUSION: The construction of
      recombinant xylanolytic B. fibrisolvens does improve the digestibility of fibre
      above that of the native, but digestibility is still less than that of the most
      potent fibre digesters such as ruminococci. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Fibre digestion may be improved by genetic manipulation of ruminal bacteria but
      ecological parameters, such as persistence in vivo and the niche of the organism,
      must be taken into account.

PMID- 11298236
TI  - Development of a dynamic continuous-discrete-continuous model describing the lag
      phase of individual bacterial cells.
AB  - AIMS: A previous model for adaptation and growth of individual bacterial cells
      was not dynamic in the lag phase, and could not be used to perform simulations of
      growth under non-isothermal conditions. The aim of the present study was to
      advance this model by adding a continuous adaptation step, prior to the discrete
      step, to form a continuous-discrete-continuous (CDC) model. METHODS AND RESULTS:
      The revised model uses four parameters: N(0), initial population; N(max), maximum
      population; p0, mean initial individual cell physiological state; SD(p0),
      standard deviation of the distribution of individual physiological states. A
      truncated normal distribution was used to generate tables of distributions to
      allow fitting of the CDC model to viable count data for Listeria monocytogenes
      grown at 5 degrees C to 35 degrees C. The p0 values increased with increasing
      SD(p0) and were, on average, greater than the corresponding population
      physiological states (h0); p0 and h0 were equivalent for individual cells.
      CONCLUSION: The CDC model has improved the ability to simulate the behaviour of
      individual bacterial cells by using a physiological state parameter and a
      distribution function to handle inter-cell variability. The stages of development
      of this model indicate the importance of physiological state parameters over the
      population lag concept, and provide a potential approach for making growth models
      more mechanistic by incorporating actual physiological events. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Individual cell behaviour is important in modelling
      bacterial growth in foods. The CDC model provides a means of improving existing
      growth models, and increases the value of mathematical modelling to the food
      industry.

PMID- 11298237
TI  - Molecular evaluation of microbial diversity occurring in different types of
      Mozzarella cheese.
AB  - AIMS: The microbial community of different types of unripened Pasta Filata cheese
      was investigated by culture-independent methods with the aim of rapidly achieving
      knowledge about cheese microbiota and discriminating traditional and industrial
      cheeses. METHODS AND RESULTS: The microbial DNA extracted directly from the
      samples was used as a template in PCR experiments to amplify the 16S-23S rDNA
      spacer region and the V3 region of the 16S rDNA. Conventional electrophoresis of
      the amplified spacers allowed known classes of these DNA fragments belonging to
      genera and species of lactic acid bacteria to be distinguished. Denaturing
      gradient gel electrophoresis analysis of V3 amplicons was supported by reference
      cultures of LAB used as markers. CONCLUSION: Both molecular approaches furnished
      the expected information about microbial diversity and were quite valid for
      discriminating industrial, semi-artisanal or traditional cheeses, characterized
      by increasingly complex DNA profiles. SIGNIFICANCE AND IMPACT OF THE STUDY: Both
      methods could be used for legal purposes when products obtained through
      prescribed manufacturing regulations are to be analysed.

PMID- 11298238
TI  - Biocontrol of Pythium in the pea rhizosphere by antifungal metabolite producing
      and non-producing Pseudomonas strains.
AB  - AIMS: Four well-described strains of Pseudomonas fluorescens were assessed for
      their effect on pea growth and their antagonistic activity against large Pythium
      ultimum inocula. METHODS AND RESULTS: The effect of Pseudomonas strains on the
      indigenous soil microflora, soil enzyme activities and plant growth in the
      presence and absence of Pythium was assessed. Pythium inoculation reduced the
      shoot and root weights, root length, and the number of lateral roots. The effect
      of Pythium was reduced by the Pseudomonas strains. Strains F113, SBW25 and CHAO
      increased shoot weights (by 20%, 22% and 35%, respectively); strains Q2-87, SBW25
      and CHAO increased root weights (14%, 14% and 52%). Strains SBW25 and CHAO
      increased root lengths (19% and 69%) and increased the number of lateral roots
      (14% and 29%). All the Pseudomonas strains reduced the number of lesions and the
      root and soil Pythium populations, while SBW25 and CHAO increased the number of
      lateral roots. Pythium inoculation increased root and soil microbial populations
      but the magnitude of this effect was Pseudomonas strain-specific. Pythium
      increased the activity of C, N and P cycle enzymes, while the Pseudomonas strains
      reduced this effect, indicating reduced plant damage. CONCLUSION: Strains SBW25
      and CHAO had the greatest beneficial characteristics, as these strains produced
      the greatest reductions in the side effects of Pythium infection (microbial
      populations and enzyme activities) and resulted in significantly improved plant
      growth. Strain SBW25 does not produce antifungal metabolites, and its biocontrol
      activity was related to a greater colonization ability in the rhizosphere.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first critical comparison of
      such important strains of Ps. fluorescens showing disease biocontrol potential.

PMID- 11298239
TI  - Detection and characterization of a bacteriocin, garviecin L1-5, produced by
      Lactococcus garvieae isolated from raw cow's milk.
AB  - AIMS: The identification of a bacteriocin-producing lactococcal strain isolated
      from raw cow's milk is reported, along with production conditions, physical and
      chemical properties, and mode of action of the bacteriocin. METHODS AND RESULTS:
      On the basis of resistance to clindamycin, species-specific PCR and amplification
      of the 16S-23S rDNA spacer region, the strain was identified as Lactococcus
      garvieae. Its bacteriocin, designated garviecin L1-5, was bactericidal against
      closely related species and strains of species from different genera, including
      Listeria monocytogenes and Clostridium spp. Garviecin L1-5 was shown to be
      proteinaceous by protease inactivation and was unaffected by heat treatments,
      also at low pH values. When amplifying known lactococcal bacteriocin genes using
      DNA from strain L1-5 as template, no amplification products were observed on the
      agarose gel. The molecular weight of garviecin L1-5 was about 2.5 kDa. As far as
      is known, no bacteriocins have been detected from Lactococcus garvieae.
      CONCLUSION: The general properties of garviecin L1-5 are characteristic of the
      low-molecular-weight bactericidal peptide group. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The survey of micro-organisms for novel antimicrobial substances provided
      valuable information on their physiology, ecology and practical application.

PMID- 11298240
TI  - A continuous culture biofilm model of cariogenic responses.
AB  - AIMS: To validate an in vitro model for the analysis of physiological and
      ecological responses to sugar challenge in bacterial populations, and subsequent
      changes in enamel mineralization. METHODS AND RESULTS: A seven-organism bacterial
      consortium was grown in a biofilm mode on enamel and hydroxyapatite (HA) surfaces
      in a continuous culture system and exposed to repeated sucrose challenges. This
      produced 'pH-cycling' conditions within the system. Populations on HA surfaces
      were enumerated. Changes in relative proportions of the different populations,
      and in the total viable count, were observed, between different treatments.
      Microradiography of the enamel sections showed increasing demineralization with
      increasing sucrose concentration. The lesions formed were similar to 'white-spot'
      lesions found in vivo. Differences in the quality of biofilms formed were also
      observed using Confocal Laser Scanning Microscopy. CONCLUSION: An in vitro model
      has been validated for the analysis of both physiological and ecological
      responses to sucrose challenges in bacterial populations, and subsequent changes
      in enamel mineralization. SIGNIFICANCE AND IMPACT OF THE STUDY: This model should
      facilitate the study of changes in bacterial populations in response to
      application of putative anticaries agents and concomitant changes in enamel
      mineralization.

PMID- 11298241
TI  - Purification and characterization of an extracellular proline iminopeptidase from
      Corynebacterium variabilis NCDO 2101.
AB  - AIMS: To screen the extracellular proteolytic and lipolytic activities of
      Corynebacterium variabilis NCDO 2101 and to purify and characterize a proline
      iminopeptidase enzyme in order to investigate the role of the major component of
      the smear of bacterial surface-ripened cheeses. METHODS AND RESULTS: Four
      chromatographic steps were used to purify the enzyme and a three-factor, five
      level Central Composite Design was used to study the interactive effects of
      cheese-related values of pH, NaCl and temperature. The proline iminopeptidase
      showed some biochemical properties different from the same enzyme purified from
      lactic acid bacteria and other smear bacteria. It tolerated NaCl concentrations
      up to 7.5% and was sensitive to low values of pH especially when they were
      combined with low temperature. CONCLUSION: The proline iminopeptidase of C.
      variabilis NCDO 2101 may have a role in proteolysis during ripening of smear
      surface-ripened cheeses. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of
      this work contribute to the knowledge of the enzymology of smear bacteria in
      order to improve the ripening of bacterial surface-ripened cheeses.

PMID- 11298242
TI  - Comparison of aerobic denitrification under high oxygen atmosphere by Thiosphaera
      pantotropha ATCC 35512 and Pseudomonas stutzeri SU2 newly isolated from the
      activated sludge of a piggery wastewater treatment system.
AB  - AIMS: This study compares the ability of Thiosphaera pantotropha ATCC 35512 and
      the newly isolated Pseudomonas stutzeri SU2 to perform aerobic denitrification.
      METHODS AND RESULTS: Nitrate-supplemented basal medium in airtight crimp-sealed
      serum bottles containing an atmosphere of 92% oxygen was inoculated with Ps.
      stutzeri SU2 or T. pantotropha and incubated at 30 degrees C. During the 92-h
      incubation period, aerobic denitrification by Ps. stutzeri SU2 (NO3(-) - N
      removal 99.24%) was more efficient than that by T. pantotropha (NO3(-) - N
      removal 27.29%). CONCLUSION: Pseudomonas stutzeri SU2, which was isolated from
      the activated sludge of a sequencing batch reactor treating piggery wastewater,
      rapidly reduced the nitrate to nitrogen gas without nitrite accumulation. The
      nitrate removal rate of SU2 was 0.032 mmol NO3(-) - N g cell-1 h-1 after 44 h
      incubation. SIGNIFICANCE AND IMPACT OF THE STUDY: Pseudomonas stutzeri SU2 can be
      used in a full-scale sequencing batch system for efficient in situ aerobic
      nitrate removal from piggery wastewater.

PMID- 11298243
TI  - The combined action of carvacrol and high hydrostatic pressure on Listeria
      monocytogenes Scott A.
AB  - AIMS: The aim of the study was to investigate the combined antimicrobial action
      of the plant-derived volatile carvacrol and high hydrostatic pressure (HHP).
      METHODS AND RESULTS: Combined treatments of carvacrol and HHP have been studied
      at different temperatures, using exponentially growing cells of Listeria
      monocytogenes, and showed a synergistic action. The antimicrobial effects were
      higher at 1 degrees C than at 8 or 20 degrees C. Furthermore, addition of
      carvacrol to cells exposed to sublethal HHP treatment caused similar reductions
      in viable numbers as simultaneous treatment with carvacrol and HHP. Synergism was
      also observed between carvacrol and HHP in semi-skimmed milk that was
      artificially contaminated with L. monocytogenes. CONCLUSION: Carvacrol and HHP
      act synergistically and the antimicrobial effects of the combined treatment are
      greater at lower temperatures. SIGNIFICANCE AND IMPACT OF THE STUDY: The study
      demonstrates the synergistic antimicrobial effect of essential oils in
      combination with HHP and indicates the potential of these combined treatments in
      food processing.

PMID- 11298244
TI  - Identification of thermophilic Campylobacter spp. by phenotypic and molecular
      methods.
AB  - AIMS: The differences between phenotyping and genotyping (polymerase chain
      reaction- restriction fragment length polymorphism) of Campylobacter jejuni,
      Campylobacter coli, Campylobacter lari and Campylobacter upsaliensis were
      assessed. METHODS AND RESULTS: A total of 51, 63 and 88 strains from dogs, pigs
      and humans, respectively, were examined. The strains were first typed by
      biochemical methods, then by PCR-RFLP using AluI and Tsp509I. None of the strains
      were typed as Camp. lari by the PCR-RFLP. The biggest differences were found in
      the identification of Camp. jejuni and Camp. coli. The main discrepancies were
      caused with the hippurate hydrolysis test and sensitivity to cephalothin and
      nalidixic acid. Strains which were identified biochemically as Camp. coli and by
      digestion with AluI as Camp. jejuni (eight strains) were tested for the presence
      of the hippuricase gene. CONCLUSION: The PCR typing results showed the presence
      of the hippuricase gene as unique to Camp. jejuni. SIGNIFICANCE AND IMPACT OF THE
      STUDY: A reliable identification of Campylobacter spp. should be supplemented
      with a molecular method.

PMID- 11298245
TI  - Effects of salinity on protein and lipopolysaccharide pattern in a salt-tolerant
      strain of Mesorhizobium ciceri.
AB  - AIMS: To characterize the physiological and metabolic responses of Mesorhizobium
      ciceri strain ch-191 to salt stress, investigating the changes induced by
      salinity in protein and lipopolysaccharide profiles, as well as determining the
      accumulation of amino acids, glutamate and proline. METHODS AND RESULTS: Strain
      ch-191 of M. ciceri was grown with different NaCl concentrations. Protein and
      lipopolysaccharide patterns were determined by electrophoresis. The strain ch-191
      tolerated up to 200 mmol l-1 NaCl, although higher salt dosages limited its
      growth and induced changes in the protein profile. The most noteworthy change in
      the LPS-I pattern was the decrease in the slowest band and the appearance of an
      intermediate mobility band. The accumulation of proline in response to salt
      stress surpassed that of glutamate. CONCLUSION: The protein profile showed major
      alterations at salinity levels which inhibited growth. However, the alterations
      in the LPS profile and accumulation of compatible solutes were evident from the
      lowest levels, suggesting that these changes may constitute adaptative responses
      to salt, allowing normal growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      selection and characterization of salt-tolerant strains, which also show
      efficient symbiotic performance under salinity, may constitute a strategy for
      improving Cicer arietinum-Mesorhizobium ciceri symbiosis in adverse environments.

PMID- 11298246
TI  - Effects of medium composition, calcium, iron and oxygen on haemolysin production
      by Plesiomonas shigelloides isolated from water.
AB  - AIMS: The effects of medium composition, calcium, iron and oxygen tension on the
      haemolytic activity of Plesiomonas shigelloides were investigated. METHODS AND
      RESULTS: The haemolytic activity of seven strains of Ple. shigelloides was tested
      on the surface of Luria Agar (LA), Brain Heart Infusion Agar (BHIA) and Trypitic
      Soy Agar (TSA) containing 5% (v/v) sheep blood, and in the Agar Overlay (AO)
      assay. All strains produced beta-haemolysis in the AO assay in three media, and
      on the surface of LA. The kinetics of growth and haemolytic activity of Ple.
      shigelloides 9P3-1 were evaluated in six different media, and the highest
      production of haemolysin occurred in Luria Broth (LB). The haemolytic activity of
      9P3-1 was stimulated by Ca2+ and inhibited by EDTA. Addition of iron to the
      culture medium did not affect bacterial growth, although it reduced bacterial
      haemolytic activity. In the presence of an iron chelator, growth of the 9P3-1 was
      inhibited, but its haemolytic activity was enhanced. CONCLUSION: The haemolytic
      activity of Ple. shigelloides depends on medium composition, and that it is
      regulated by iron and is calcium-dependent. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These results show the importance of optimization of media composition and oxygen
      tension for detection of Ple. shigelloides haemolytic activity.

PMID- 11298247
TI  - Correlations between clinical and historical variables, and cerebral structural
      variables in people with mild intellectual disability and schizophrenia.
AB  - The increased prevalence of schizophrenia in the population with mildly
      intellectual disability (ID) remains unexplained. The present study explores
      several possibilities by examining historical/clinical findings in relation to
      structural neuroimaging findings in three groups: (1) comorbid mild ID and
      schizophrenia; (2) schizophrenia alone; and (3) mild ID alone. Information about
      clinical and historical variables was obtained from 101 subjects (39 with
      comorbidity, 34 with schizophrenia and 28 with mild ID), out of whom 68 (23, 25
      and 20, respectively) had had a cerebral magnetic resonance imaging (MRI) scan.
      Although a number of significant correlations exist between clinical variables
      and structural MRI abnormalities in all three groups, no clearly predictive inter
      or between-group differences emerged. More striking was the finding that showed
      small amygdalo-hippocampal size to be associated with a history of central
      nervous system injury, especially meningitis. These findings provide support for
      the view that cognitive impairment and comorbid psychosis can result from a
      common cause, such as meningitis or obstetric complications, possibly interacting
      with other factors, such as family history.

PMID- 11298248
TI  - Psychopathology and young people with Down's syndrome: childhood predictors and
      adult outcome of disorder.
AB  - There is a scarcity of follow-up studies into adult life of psychiatric disorder
      in young people with intellectual disability. The key aims of the present study
      were: (1) to determine the outcome of psychopathology present in childhood in
      individuals with Down's syndrome (DS); and (2) to look at childhood predictors of
      adult psychiatric disorder. Fifty-two young people with DS were identified from a
      sample of 193 subjects examined in childhood and adolescence for psychiatric and
      behaviour disorder. These young adults were interviewed for the presence of
      psychiatric disorder. No significant relationship was found between childhood
      mental disorder and psychiatric disorder in adult life for those individuals with
      DS. Early childhood factors of psychiatric disorder, challenging behaviour and
      family environment, except social background, did not predict adult
      psychopathology in young people with DS. Childhood disorder in individuals with
      DS has a good early prognosis with little evidence of continuity of the disorder
      into adult life.

PMID- 11298249
TI  - Association between perceived social support and strain, and positive and
      negative outcome for adults with mild intellectual disability.
AB  - Social strain has been identified as a trigger for both depression and physical
      health problems, but has not been well researched in people with intellectual
      disability (ID). The present study contrasted the effects of social support with
      social strain on depressive symptoms, somatic complaints and quality of life over
      time in adults with mild ID. The level of social support explained a significant
      proportion of variance in quality of life 6 months later, but not depressive
      symptoms or somatic complaints. In contrast, the level of social strain accounted
      for a significant proportion of variance in depressive symptoms and somatic
      complaints 6 months later, but not quality of life. The results suggest that
      interpersonal relationships can be both positively and negatively associated with
      physical and mental health for people with ID.

PMID- 11298250
TI  - Diagnosis of depression in people with severe/profound intellectual disability.
AB  - The Marston 30 Symptoms Checklist for detecting depression was used to determine
      whether or not the notion of 'depressive equivalents' can provide a few of the
      core characteristics necessary for the diagnosis of depressive disorders in
      people with severe/profound intellectual disability (ID). Diagnoses of major
      depression were made by a psychiatrist using the DSM-III-R criteria, combined
      with information from records, staff, team, parents, behaviour profiles, direct
      observations, mental status and follow-up visits. Twenty-two people with ID
      fulfilled the selection criteria from a larger sample of 150 patients who had
      been evaluated in 350 contact visits. Scores on the checklist for major
      depression for 15 subjects with severe/profound ID were similar to the core
      characteristics for diagnosis of major depression by DSM-III-R criteria. Evidence
      was found for the presence of depressive equivalents in the subjects, but these
      appeared to be secondary. The 15 participants with severe/profound ID were
      observed mostly during the depressive phase of bipolar I and bipolar II disorder,
      and major depression, recurrent type. Melancholic features were prominent in
      their presentation. Further studies of people with ID are needed to determine
      whether depressive equivalents are more prominent in cases of major depression
      with atypical features than in cases of major depression with melancholic
      features.

PMID- 11298251
TI  - Self-injurious behaviour before and after deinstitutionalization.
AB  - The deinstitutionalization movement is presently spreading in Europe. Studies
      evaluating the effects of deinstitutionalization on behaviour disturbances among
      people with intellectual disability (ID) have been inconclusive. The present
      paper focuses on people without self-injurious behaviour (SIB) who developed SIB
      after deinstitutionalization. The present authors studied individual and
      environmental characteristics before and after deinstitutionalization to look for
      factors associated with the development of SIB which could also be possible
      intervention points for preventive action. All those individuals in an
      institution for people with ID who did not have SIB before deinstitutionalization
      were included in the present study. The individuals who developed SIB after
      deinstitutionalization (n = 15) formed the study group (group A) and those who
      did not (n = 53) comprised the control group (group B). The population was
      examined both before and after deinstitutionalization. As far as possible, the
      same methods were used at both occasions. The covariates were both individual
      (e.g. mental health, behaviour disturbances and behaviour deficits) and
      environmental (e.g. caretaker education, caretaker:patient ratio, housing and
      leisure activities). Psychiatric disorders were identified in 1987 and 1995 with
      the Psychopathology Instrument for Mentally Retarded Adults, which was filled in
      by the caretakers. In 1987, the people in group A who acquired SIB had lower
      developmental quotients, used wheelchairs more often and had trouble with moving
      around without help. They also had a greater frequency of epileptic seizures, and
      hearing and communication impairment. In 1995, there were only minor
      environmental differences between groups A and B. There were significantly more
      individuals involved in the rotation period and more unskilled caretakers working
      with the people in group A than group B. The present authors found no differences
      between the two groups on variables such as global mental health and behaviour
      disturbances, or in the use of neuroleptics before or after
      deinstitutionalization. Groups A and B did not show differences in behaviour
      disturbances or psychiatric disorders in 1987. In both 1987 and 1995, there were
      no differences between groups A and B on variables such as accommodation,
      caretaker:patient ratio, the number of caretakers involved in direct care, the
      caretakers' education, or the time spent in structured activities before and
      after deinstitutionalization. The individual characteristics indicating that a
      person may acquire SIB are behaviour deficits which are suggestive of central
      nervous system dysfunction or damage, even if the results are inconclusive. The
      development of SIB may also be facilitated by communication deficits or by
      reinforcement of a incidentally occurring SIB if the staff includes many
      unskilled caretakers in the rotation period.

PMID- 11298252
TI  - Challenging behaviour in community services.
AB  - The implementation of community care in the UK has led to the requirement that
      services should be able to meet the needs of adults with intellectual disability
      (ID) and additional needs in terms of challenging behaviour. However, the extent
      to which people with challenging behaviour are present in the community and the
      extent to which community services can support them effectively still requires
      significant research. The present study examines the prevalence of challenging
      behaviour amongst adults with ID residing in three London boroughs and the issues
      which arise from service delivery to this client group. All service providers and
      general practitioners in the area were contacted and asked to identify any
      individuals with ID and challenging behaviour. All responses were screened, and
      then key staff were interviewed for information on a range of demographic factors
      and on the Checklist of Challenging Behaviour. The reliability of the instrument
      was also assessed. Four hundred and forty-eight individuals were identified from
      a total borough population of 670 000. There was consistency in the types of
      behaviour which were frequently identified across the three boroughs. There were
      significant levels of self-injury as well as a range of behaviours of the 'hard
      to engage' type. Most individuals had more then one challenging behaviour and
      some individuals with seriously aggressive behaviour used local community
      services. Twenty-five per cent of the sample lived at home with their families
      and 50% were in community residential services. The boroughs differed in their
      ability to manage those with challenging behaviour in that one borough had many
      more people placed out-of-borough. Significant numbers of individuals with
      challenging behaviour were living in the community. The range and number of
      behaviours suggest that staff need to be very skilled in supporting such
      individuals, and that effective planning and support are essential if people with
      challenging behaviour are to be maintained in community settings.

PMID- 11298253
TI  - Adjunctive gabapentin in patients with intellectual disability and bipolar
      spectrum disorders.
AB  - The aim of the present study was to assess the efficacy of adjunctive gabapentin
      (GBP) in the treatment of patients with intellectual disability (ID) and bipolar
      spectrum disorders. Ten affected subjects with demonstrable increases in
      symptomatology during 'significant' life events which had interfered with or
      induced the interruption of their rehabilitation programmes were chosen for this
      study. The meaning of 'significant' was defined for each patient as a frequently
      repeated life event which had elicited a marked increase in symptoms on at least
      two occasions. Gabapentin (300-900 mg day-1) was added to the standard therapy.
      The subjects' psychopathological conditions during the significant life event
      were assessed by means of standardized tools both before and after adjunctive
      therapy with GBP. A positive response to therapy was observed, with subsequent
      improvement of psychopathological conditions, particularly for anxiety and
      depressive symptoms. The promising results obtained with GBP suggest the need for
      further trials. Adjunctive GBP may become an alternative treatment approach for
      patients with ID in whom traditional mood-stabilizing agents have frequent
      contraindications.

PMID- 11298254
TI  - Randomized trial of psychotropic medication information leaflets for people with
      intellectual disability.
AB  - People with intellectual disability (ID), like other patient groups, are known to
      have a limited knowledge of medication. Leaflets are seen as an appropriate means
      of providing patient information. To test the hypothesis that medication
      information leaflets would improve the knowledge and care of the target group,
      the present authors designed a randomized trial and planned to do subgroup
      analyses where appropriate. The participants were individually randomized to two
      groups. A control group was given verbal medication information by their nurse or
      psychiatrist, and a study group was given specifically designed leaflets in
      addition to verbal information. The present authors recruited 54 people with mild
      to moderate ID and mental illness, aged 18 years and older, who were taking
      psychiatric medications. Questionnaires administered by a blind interviewer
      recorded outcomes such as medication knowledge and satisfaction at two time
      points. The participants with mild ID in the leaflet group had significantly
      reduced medication knowledge and understanding. There were no significant
      differences in satisfaction with clinicians and medication. Patient information
      leaflets may confuse people with mild ID in the short term. Other patient groups
      with cognitive deficits may have similar outcomes. Evaluation of outcomes of
      health education initiatives is important.

PMID- 11298255
TI  - Hyponatremia during carbamazepine therapy in patients with intellectual
      disability.
AB  - Carbamazepine is an anticonvulsant and psychotropic medication commonly used in
      the treatment of people with intellectual disability (ID). The incidence of
      hyponatremia during treatment in this population is unclear. The present study
      aimed to determine the prevalence of hyponatremia during carbamazepine treatment
      in patients with ID, and to investigate the risk factors and clinical features of
      this condition. The prevalence of hyponatremia was retrospectively assessed in 53
      people receiving carbamazepine (subject group) and 64 people not receiving
      carbamazepine (control group) who lived in a residential centre for people with
      ID. The relationship between serum sodium level, sex, age, daily carbamazepine
      dose and serum carbamazepine levels was examined. The prevalence of the clinical
      features of hyponatremia was assessed in this population using a checklist. The
      prevalence of hyponatremia was 41.5% and 9.4% in the subject and control groups,
      respectively. The mean serum sodium level in the subject group was significantly
      lower than that in the control group. Hyponatremia correlates significantly with
      a high daily carbamazepine dose and a high serum carbamazepine level. The
      checklist of clinical features was not useful in detecting hyponatremia
      clinically. Hyponatremia is a common occurrence in this population. In the light
      of the uncertain significance of mild, chronic hyponatremia, the value of routine
      monitoring of serum electrolytes has yet to be established.

PMID- 11298256
TI  - Working memory and everyday cognition in adults with Down's syndrome.
AB  - A number of previous studies have suggested that young people with Down's
      syndrome (DS) have a specific deficit of the phonological loop component of the
      working memory. However, there have also been studies which have proposed a
      specific deficit of the central executive component of working memory and
      suggested similarities of working memory functioning with patients with
      Alzheimer's disease. Fifteen middle-aged people with DS were matched for their
      individual scores of non-verbal intelligence to 15 individuals with mixed
      aetiology of intellectual disability. A versatile range of tasks was used in
      order to evaluate the functioning of working memory components. In addition,
      several everyday cognition skills were assessed. The subjects with DS performed
      significantly more poorly in all tasks assessing the phonological loop.
      Performance in other working memory tasks and compound variables representing
      different working memory components was equal in the groups. In addition, both
      groups had equal everyday cognition skills. The functioning of the phonological
      loop seems to be clearly deficient in people with DS. Interestingly, the deficit
      does not seem to affect the vocabulary or other everyday cognition skills in
      individuals with DS. No signs of specific deficit of the central executive
      component of working memory were found.

PMID- 11298257
TI  - Neuropsychological assessment of patients with severe neuromotor and verbal
      disabilities.
AB  - In people with cerebral palsy, severe neuromotor disability and communication
      problems make standard neuropsychological tests impossible. Therefore,
      alternative methods and specific aids must be developed to allow patients to
      autonomously respond to the examiner's questions. In the present individuals and
      study, a neuropsychological evaluation was made of a group of eight individuals
      with cerebral palsy, and severe neuromotor and verbal disabilities, and a group
      of 19 normal subjects matched for mental age. The tests were administered using
      an autonomous selection method in which the patient selects the various responses
      through specific aids without the examiner's interference. Patients' group
      performances in visuo-spatial and memory tests were on average lower than the
      mean of the control group. In the verbal domain, patients' scores were comparable
      to those of normal children in all tests but one assessing the comprehension of
      syntactically complex sentences. An analysis of the patients' individual
      performances also revealed heterogeneous cognitive profiles: some patients
      presented a homogeneously distributed cognitive impairment and others a more
      selective one. This finding is particularly important for planning differentiated
      learning programmes, and identifying suitable communicative instruments in
      rehabilitative and educational settings.

PMID- 11298258
TI  - The structure of the bilaminar zone in the human temporomandibular joint: a light
      and scanning electron microscopy study in young and elderly subjects.
AB  - The bilaminar zone (BZ) in the human temporomandibular joint (TMJ) of toothed
      adults (GI) and toothless, elderly humans (GII) were analysed using light and
      scanning electron microscopy (SEM). In both groups the BZ consists of an upper
      and a lower stratum of connective tissue separated by a vascularized middle
      region. The superior stratum contains bundles of collagen fibres disposed in
      different directions. The fibres are fairly thick and transversely oriented
      immediately posterior to the TMJ disc. The initial part of the inferior stratum
      contains curved bundles of collagen fibres oriented anterio-posteriorly. From the
      middle to the posterior part of the inferior stratum, the fibres are right
      aligned in GI and clearly sinuous in nature in GII. In both groups, the middle
      and posterior portions of the middle region are distinguished by the presence of
      vessels and vascular spaces. Loosely arranged connective and adipose tissues are
      also evident. The vascular spaces are wider in GII than in GI. The predominance
      of type I collagen fibres is clear in all regions of the BZ in both groups. The
      elastic fibres lie parallel to the collagen fibres in both groups and they are
      thicker and more abundant in GI, apparently decreasing in GII.

PMID- 11298259
TI  - Survival rate and fracture strength of incisors restored with different post and
      core systems after exposure in the artificial mouth.
AB  - The survival rate and fracture resistance of 40 decapitated endodontically
      treated maxillary central incisors using four different post and core systems
      covered with all-ceramic copings was evaluated after exposure in the artificial
      mouth. Ten samples of the following post and core systems were investigated: high
      precious metal post (Permador) and core (Olympia) (A), zirconia post (Cerapost)
      with a pre-fabricated bonded ceramic core (Ceracap) (B), resin-ceramic post
      (experimental) with a pre-fabricated bonded ceramic core (Ceracap(R)) (C) and a
      zirconia post (Cerapost) with a custom made ceramic core (Cosmo Ingots) (D). The
      all-ceramic copings (Procera) were cemented using Panavia TC. The survival rates
      after 1 200 000 cycles in the artificial mouth are as follows: 90% (A), 80% (B),
      60% (C) and 100% (D). The results of the means and standard deviations (s.d.) of
      the fracture resistance during static loading are: 1270 +/- 312.5 (A), 1494.5 +/-
      333.5 (B), 1146.7 +/- 182.6 (C) and 463.3 +/- 46.2 (D). There are statistically
      significant differences between all groups with the exception of A and B, and A
      and C (Wilcoxon test). None of the zirconia posts with custom made ceramic cores
      covered with all-ceramic copings fractured during dynamic loading in the
      artificial mouth. The mean fracture strength during static loading was less
      favourable than that of groups A, B and C but above the clinical necessary level.

PMID- 11298260
TI  - Anatomical study of the pyramidal process of the palatine bone in relation to
      implant placement in the posterior maxilla.
AB  - The placement of dental implants in the molar region of the maxilla is often
      difficult because of insufficient bone volume and the inferior bone quality. In
      order to avoid these limitations, the pillar of bone, which is composed of the
      maxillary tuberosity, the pyramidal process of the palatine bone and the
      pterygoid process of the sphenoid bone, was introduced for implant placement. In
      fact, the pyramidal process is the posterior structure where implants are placed
      but until now, there is no available data of the size or shape of the pyramidal
      process. Therefore, we measured the height, anteroposterior distance and
      mediolateral distance of the pyramidal process and observed the shape of lateral
      and posterior surfaces of the pyramidal process of 54 Korean edentulous dry
      skulls in this study. The height was 13.1 mm (male: 13.6 mm, female: 12.4 mm).
      The anteroposterior distance was 6.5 mm (male: 6.7 mm, female: 6.1 mm). The
      mediolateral distance was 9.5 mm (male: 9.9 mm, female: 9.0 mm). The most common
      type was the right-angled triangle in the lateral surface (44.4%) and in the
      posterior surface (66.7%). There was no statistical significance between the male
      and the female in all items (P > 0.05). These results provide anatomical features
      in relation to placement of dental implants in the molar region of the maxilla
      and would be useful in treatment planning of partially or completely edentulous
      patients.

PMID- 11298261
TI  - Determination of elastic properties of metal alloys and dental porcelains.
AB  - This study aimed to determine Young's modulus, shear modulus and Poisson's ratio
      of some metal alloys and dental porcelains used in fixed prosthodontics using the
      technique of impulse excitation of vibration. It also aimed to compare Young's
      modulus values of these materials with those obtained using the other two
      methods: the four-point flexural test and the indentation test using the ultra
      micro-indentation system (UMIS). Five types of metal alloys and four types of
      dental porcelains were tested. The samples were prepared to a rectangular shape
      of approximately 8 x 30 x 1.5 mm. Frequency of vibration in a sample was read
      when a singular elastic strike was made with an impulse tool. The elastic
      constants were calculated from the frequency of vibration, dimension and mass of
      each sample. Young's modulus values resulting from the impulse excitation of
      vibration are not significantly different (P<0.05) from those obtained using the
      flexural test and the UMIS test in most metal alloys but are different in
      titanium, titanium alloy and most of the dental porcelains. The technique of
      impulse excitation of vibration has proven to be an accurate method and is simple
      to operate. The elastic properties of these alloys and porcelains are essential
      for determining the other mechanical properties (fracture toughness) and are
      relevant in clinical application.

PMID- 11298262
TI  - The relationship between selective sleep deprivation, nocturnal jaw-muscle
      activity and pain in healthy men.
AB  - The relationship between nocturnal jaw-muscle activity and temporomandibular
      disorders (TMD) is still controversial. The aim of this study was to investigate
      the effect of selective slow wave sleep (SWS = non-rapid-eye-movement (NREM)
      stage 3 + 4) deprivation on jaw-muscle activity using a new automatic system. Ten
      healthy men without signs of symptoms of TMD participated. The subjects slept in
      the laboratory for six continuous nights including one adjustment night, one
      baseline night, three nights with experimental sleep deprivation and one recovery
      night. Polysomnographic recordings of electroencephalography (EEG) and
      electromyography (EMG) were obtained for recognition of sleep stages and masseter
      muscle activity. During the three experimental nights, computer-controlled sound
      stimulation (60--90 dB(A), 1000 Hz) were given as long as the subjects were in
      SWS. Maximum voluntary occlusal force (MVOF), pain pressure threshold (PPT) and
      visual analogue scales (VAS) were used to assess the state of the masseter
      muscles every morning and evening during the study period. The results showed
      that the time spent in SWS was significantly decreased during the first sleep
      deprivation night, but there were no significant effects on nocturnal EMG
      activity (i.e. the numbers of bruxism episodes per hour of sleep, bruxism bursts
      per episodes bruxism bursts per hour of sleep), MVOF, VAS or PPT. Furthermore,
      the automatic system only deprived the SWS in five subjects for the following two
      nights although the sound stimulation was given at the maximum intensity. These
      results suggest that deprivation of SWS may not interact immediately with
      nocturnal jaw-muscle activity and jaw-muscle pain.

PMID- 11298263
TI  - Comparative study of maxillary complete dentures constructed of metal base and
      metal structure framework.
AB  - A removable denture designed using a three-dimensional cast metal framework
      (hereafter referred to as the 'structurally designed' denture) could extend
      denture longevity because it is unbreakable and easy to adjust. The aim of the
      present clinical study was to compare two types of maxillary removable dentures:
      conventional dentures and structurally designed denture. One edentulous and five
      partially dentate patients were fitted with two maxillary dentures made from the
      same impression and same occlusal relationship. About 20 days after delivery of
      the denture, masticatory analysis was conducted chewing phase (open, closed, and
      occluded); coefficients of variation and average variation were calculated.
      Denture vibration during tapping was then measured using an accelerometer. The
      patients were also interviewed about comfort, ease of chewing, speech, stability,
      aesthetics and preference for regular use. For both masticatory movements and
      denture vibration, there were no significant differences (P>0.1) between the
      conventional denture and the structural design denture. In evaluating the
      dentures according to each criteria, the significant superiority of one denture
      over the other could not be determined. However, all patients subjectively
      preferred the structurally designed dentures for regular use. According to these
      findings, structurally designed dentures do not appear to have any particular
      physiological problems as compared with the conventional dentures.

PMID- 11298264
TI  - Antibacterial properties of dentin bonding systems, polyacid-modified composite
      resins and composite resins.
AB  - This study examined the antibacterial activities of the bonding systems Syntac,
      EBS and Scotchbond 1, the polyacid-modified composite resins Hytac and
      Compoglass, and the composite resins Tetric, Z100 and Scalp-it. They were
      evaluated using the cariogenic bacteria Streptococcus mutans, Lactobacillus
      salivarius, Streptococcus sorbinus and Actinomyces viscosus in vitro with a
      modified cylinder drop plate agar diffusion assay. All adhesives of the dentin
      bonding systems and the polyacid-modified composite resins exhibited various
      degrees of antibacterial activity against all of the test bacteria. On the
      contrary, composite resins did not affect bacterial growth. The data suggest that
      the use of these adhesives and polyacid-modified composite resins may reduce the
      consequences of microleakage owing to their antibacterial properties.

PMID- 11298265
TI  - Functional-rhythmical coupling of head and mandibular movements.
AB  - It is known that small head movements accompany the movements of the jaw during
      mastication; however, it is unknown whether these movements occur rhythmically
      and synchronously. The objective of this study was to determine whether there
      exists a functional coupling between the head and mandibular movements. Four
      healthy male adults (mean age 25.5) with normal occlusion and without TMD history
      were selected as subjects. Using the Trimet system, we measured tridimensionally
      both the movement of the head and the mandible by tracking upper and lower
      incisal points, respectively, during tapping movements with different opening
      range and frequency, then analysed the vertical component of these movements. The
      upper incisal point moved in opposite direction to the mandible in all tapping
      strokes in all subjects, during opening the head moved in a cranial direction and
      during closing in a caudal direction; the incidence rate for this concomitant
      movement was 98%, implying that the head moves periodically and rhythmically, as
      the mandible does. The cycle time of these coincident movements showed a
      correlation coefficient of 0.94. Moreover, the vertical range of head movement
      was within 10% of the jaw's movement. From these results we concluded that, at
      least during teeth tapping, the head moves in rhythmical coordination with
      mandibular movement.

PMID- 11298266
TI  - Effect of three adhesive primers on the bond strengths of four light-activated
      opaque resins to noble alloy.
AB  - The effect of commercial adhesive primers for noble metals on the bond strength
      of light-activated opaque resin has not been determined. This study evaluated the
      effect of three adhesive primers on the shear bond strengths of each of the four
      light-activated opaque resins to silver--palladium--copper--gold (Ag--Pd--Cu--Au)
      alloy. The adhesive primers Alloy Primer (AP), Metal Primer II (MPII) and
      Metaltite(MT) were used. Four commercial light-activated opaque resins (Axis
      (AX), Cesead II (CEII), Dentacolor(DE) and Solidex (SO) were used to bond a light
      activated resin-veneered composite to Ag--Pd--Cu--Au alloy. The specimens were
      stored in water at 37 degrees C for 24 h and then immersed alternatively in water
      baths at 4 and 60 degrees C for 1 min each for up to 20,000 thermal cycles before
      shear mode testing at a cross-head speed of 0.5 mm min(-1). All the primers
      examined improved the shear bond strength between opaque resin and Ag--Pd--Cu--Au
      alloy compared with non-primed specimens prior to thermal cycling. After 20,000
      thermal cycles, the bond strengths of combined use of AP and DE and that of MT
      and each of AX, CE or DE were significantly greater than any other groups.
      Significant difference was observed between the bond strengths at thermal cycles
      0 and 20,000, with the combined use of MT and DE. With the combination of
      appropriate adhesive metal primers and light-activated opaque resins, complicated
      surface preparations of metal frameworks of resin-veneered prostheses that are
      composed of casting Ag-Pd-Cu-Au alloy may be negligible.

PMID- 11298267
TI  - Relaxation rate in the assessment of masseter muscle fatigue.
AB  - The aim of this study was to assess a simple method of measuring relaxation rate
      in the jaw-closing system for the purpose of quantifying jaw muscle fatigue. A
      summary of the various different methods of measuring relaxation rate is also
      provided. The rates of twitch contraction and relaxation were measured in 30
      symptom-free subjects following bilateral direct electrical stimulation of the
      masseter muscles. The resulting twitch force was recorded via a force transducer
      placed between the anterior teeth. The transducer was held between the teeth with
      as little force as possible while four single stimuli were delivered at 5-s
      intervals. The stimulating electrodes were then removed and replaced and the
      experiment was repeated. The force records of the resulting twitches were
      averaged and the half-contraction time, twitch amplitude and half-relaxation time
      were measured. There was a significant difference in half-relaxation time between
      males and females, being faster in females (P=0.0045, independent t-test). No
      significant difference was found in twitch amplitude and half-contraction time
      between males and females. Half-relaxation time and half-contraction time were
      independent of twitch amplitude. This method of measuring the relaxation rate of
      the masseter muscles was found to be practical and the results were reproducible
      between sessions.

PMID- 11298268
TI  - Effect of the reducing agent on the oxygen-inhibited layer of the cross-linked
      reline material.
AB  - The purpose of this study was to clarify the effect of the reducing agent on the
      oxygen-inhibited layer of the cross-linked reline material. A commercial
      autopolymerizing reline resin containing 1,6-hexanediol dimethacrylate as cross
      linking agent and 1 wt.% sodium sulphite solution as a reducing agent was
      prepared. The inhibited layer was observed using an optical transmission
      microscope under the conditions of the application of sodium sulphite for 0, 1, 5
      and 15 min after curing for 10 min in air. As a control, the reline material was
      cured on sealing from air. Moreover, the three-point flexural strength test was
      performed under the same conditions. The fracture was then observed using
      scanning electron microscopy (SEM). Although hardness of the inhibited layer was
      enhanced after the application of the reducing agent, the layer was still
      observed. The flexural strength of the control and the groups after application
      of the reducing agent was significantly higher than the group without reducing
      agent. SEM examination revealed many polymer beads on the group without reducing
      agent, whereas polymer beads could not be observed on the groups applying the
      reducing agent. These results indicated that the application of sodium sulphite
      was effective in hardening the surface unpolymerized zone.

PMID- 11298269
TI  - Thermal analysis on the cure speed of dual cured resin cements under porcelain
      inlays.
AB  - The reaction kinetics of five commercial dual cured resin cements (Bistite, Dual,
      Scotchbond, Duolink and Duo) were investigated when cured under varying
      thicknesses of porcelain inlays by chemical or light activation. The effect of
      the porcelain disc on the rate of polymerization of dual cured resin cement
      during light exposure was evaluated using thermal analysis, thermogravimetric
      analysis and differential scanning calorimetry. Inorganic filler weight %, the
      heat of cure (Delta H), the maximum rate of heat output and the peak heat flow
      time were measured when the polymerization reaction occurred by chemical cure
      only or by light exposure through 1, 2 and 4-mm thick porcelain discs. In 4-mm
      thick porcelain discs, the exposure time was varied from 40 to 60 s to
      investigate the effect of the exposure time on polymerization reaction. Cure
      speed by light exposure was 5--20 times faster than by chemical cure. The dual
      cured resin cements differed markedly in their sensitivity to light and chemical
      activation. The peak heat flow time increased by 1.51, 1.87 and 3.24 times as
      light cure was carried out through 1, 2 and 4-mm thick porcelain discs,
      respectively. Exposure times recommended by the manufacturers were insufficient
      to compensate for the attenuation of light by the 4-mm thick porcelain disc.

PMID- 11298270
TI  - Relationship of third molar development and root angulation.
AB  - Angled roots are seen in mandibular third molars, which have a high frequency of
      incomplete impaction. We examined the relationship between incomplete impaction
      and angled roots. We enrolled orthopantomographs to determine the prevalence of
      angled roots in 239 men and 222 women aged 21--35 years with bilateral mandibular
      third molars. Angled roots were more frequent in subjects in whom the third
      molars had a different status on each side than in those with the same status on
      both sides (men: P<0.05; women: P<0.01). The incidence of women with angled roots
      in those with bilateral incomplete impactions was higher than that in those with
      bilateral eruption (P<0.01). Angled roots among mandibular third molars are
      related to environmental factors. Angled roots occur more frequently in women
      with incomplete impaction than in those with full eruption.

PMID- 11298271
TI  - No syringes please, ejection of phage T7 DNA from the virion is enzyme driven.
AB  - Development of a sensitive assay that measures the rate of cellular
      internalization of an infecting bacteriophage T7 genome has led to surprising
      observations on the initiation of infection. Proteins ejected from the phage
      virion probably function as an extensible tail to form a channel across the cell
      envelope. This channel is subsequently used for translocating the phage genome
      into the cell. One of these ejected proteins also controls the amount of DNA that
      enters the cell, rendering subsequent internalization of the remainder of the
      genome dependent on transcription. Mutations affecting this protein allow the
      entire phage genome to enter a cell by the transcription-independent process.
      This process exhibits pseudo-zero-order reaction kinetics and a temperature
      dependence of translocation rate that are not expected if DNA ejection from a
      phage capsid were caused by a physical process. The temperature dependence of
      transcription-independent T7 DNA translocation rate is similar to those of enzyme
      catalysed reactions. Current data suggest a highly speculative model, in which
      two of the proteins ejected from the phage head establish a molecular motor that
      ratchets the phage genome into the cell.

PMID- 11298272
TI  - Bacillus subtilis mutations that alter the pathway of phosphorylation of the anti
      anti-sigmaF factor SpoIIAA lead to a Spo- phenotype.
AB  - Sigma-F, the first sporulation-specific transcription factor of Bacillus
      subtilis, is regulated by an anti-sigma factor SpoIIAB, which can also act as a
      protein kinase that phosphorylates the anti-anti-sigma factor SpoIIAA. The time
      course of phosphorylation reaction is biphasic, a fact that has been interpreted
      in terms of a mechanism for sequestering SpoIIAB away from sigmaF and thus
      allowing activation of sigmaF when needed. Site-directed mutagenesis of SpoIIAA
      has allowed us to isolate two mutants that cannot activate sigmaF and which are
      therefore Spo-. The two mutant SpoIIAA proteins, SpoIIAAL61A and SpoIIAAL90A, are
      phosphorylated with linear kinetics; in addition they are less able to form the
      stable non-covalent complex that wild-type SpoIIAA makes with SpoIIAB in the
      presence of ADP. The phosphorylated form of SpoIIAAL90A was hydrolysed by the
      specific phosphatase SpoIIE at the same rate as wild-type SpoIIAA-P, but the rate
      of hydrolysis of SpoIIAAL61A-P was much slower. The secondary structure and the
      global fold of the mutant proteins were unchanged from the wild type. The results
      are interpreted in terms of a model for the wild type in which SpoIIAB, after
      phosphorylating SpoIIAA, is released in a form that is tightly bound to ADP and
      which then makes a ternary complex with an unreacted SpoIIAA. We propose that it
      is the inability to make this ternary complex that deprives the mutant cells of a
      means of keeping SpoIIAB from inhibiting sigmaF.

PMID- 11298273
TI  - Large-scale monitoring of pleiotropic regulation of gene expression by the
      prokaryotic nucleoid-associated protein, H-NS.
AB  - Despite many years of intense work investigating the function of nucleoid
      associated proteins in prokaryotes, their role in bacterial physiology remains
      largely unknown. The two-dimensional protein patterns were compared and
      expression profiling was carried out on H-NS-deficient and wild-type strains of
      Escherichia coli K-12. The expression of approximately 5% of the genes and/or the
      accumulation of their protein was directly or indirectly altered in the hns
      mutant strain. About one-fifth of these genes encode proteins that are involved
      in transcription or translation and one-third are known to or were in silico
      predicted to encode cell envelope components or proteins that are usually
      involved in bacterial adaptation to changes in environmental conditions. The
      increased expression of several genes in the mutant resulted in a better ability
      of this strain to survive at low pH and high osmolarity than the wild-type
      strain. In particular, the putative regulator, YhiX, plays a central role in the
      H-NS control of genes required in the glutamate-dependent acid stress response.
      These results suggest that there is a strong relationship between the H-NS
      regulon and the maintenance of intracellular homeostasis.

PMID- 11298274
TI  - Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell
      activation.
AB  - Fimbriae mediate bacterial attachment to host cells and provide a mechanism for
      tissue attack. They activate a host response by delivery of microbial products
      such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling
      mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger
      cytokine responses in CD14 negative host cells. Here we show that P fimbriae
      utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal
      inflammation. Escherichia coli strains expressing P fimbriae as their only
      virulence factor stimulated chemokine and neutrophil responses in the urinary
      tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to
      infection. Mucosal cells were CD14 negative but expressed several TLR species
      including TLR4, and TLR4 protein was detected. Infection with P fimbriated
      bacteria stimulated an increase in TLR4 mRNA levels. The activation signal did
      not involve the LPS-CD14 pathway and was independent of lipid A myristoylation,
      as shown by mutational inactivation of the msbB gene. Co-staining experiments
      revealed that TLR4 and the GSL receptors for P fimbriae co-localized in the cell
      membrane. The results demonstrate that P fimbriae activate epithelial cells by
      means of a TLR4-dependent signalling pathway, and suggest that GSL receptors for
      P fimbriae can recruit TLR4 as co-receptors.

PMID- 11298275
TI  - A ComGA-dependent checkpoint limits growth during the escape from competence.
AB  - In Bacillus subtilis, competence for transformation develops in 5-10% of the
      cells in a stationary phase culture. These cells exhibit a prolonged lag in the
      resumption of growth and cell division during the escape from competence. To
      better understand the basis of this lag, we have characterized competent cultures
      microscopically. To distinguish the minority of competent cells, a translational
      fusion between ComK, the competence transcription factor, and the green
      fluorescent protein (GFP) was used as a marker. Only 5-10% of the cells in a
      competent culture were fluorescent, indicating that ComK synthesis is an all or
      nothing event. To validate the identification of competent cells, we demonstrated
      the coincident expression of comEA, a late competence gene, and comK-gfp.
      Competent cells resemble stationary phase cells; the majority are single (not in
      chains), contain single nucleoids, and rarely contain FtsZ rings. Upon dilution
      into fresh medium, competent cells maintain this appearance for about 2 h. In
      contrast, the majority of non-competent cells rapidly resume growth, exhibiting
      chaining, nuclear division and FtsZ-ring formation. The late competence protein
      ComGA is required for the competence-related block in chromosome replication and
      cell division. In the competent cells of a comGA mutant culture, chromosomal
      replication and FtsZ-ring formation were no longer blocked, although competent
      comGA mutant cells were abnormal in appearance. It is likely that one role for
      ComGA is to prevent growth, chromosome replication and cell division until ComK
      can be eliminated by degradation. A mutation in the ATP-binding site of comGA
      inactivated the protein for transformation but did not prevent it from inhibiting
      DNA replication and cell division. The buoyant density difference between
      competent and non-competent cells depends on the competence-specific growth
      arrest.

PMID- 11298276
TI  - Subcellular localization and characterization of chorismate synthase in the
      apicomplexan Plasmodium falciparum.
AB  - The resurgence of drug-resistant apicomplexa, in particular Plasmodium
      falciparum, the most fatal human malarial parasite, has focused attention on the
      recent discovery of the shikimate pathway in these organisms, as it may provide
      the urgently required, novel drug targets resulting from the absence of this
      pathway in mammals. The direction of a parasiticidal drug design programme
      obviously requires knowledge of the subcellular localization and indeed full
      characterization of the possible enzyme targets. Here, we report the cloning and
      characterization of chorismate synthase from P. falciparum and present the first
      biochemical and immunological studies of an enzyme of the shikimate pathway from
      an apicomplexan parasite. We show that this chorismate synthase does not possess
      an intrinsic flavin reductase activity and is therefore monofunctional like the
      plant and bacterial chorismate synthases. Highest immunological cross-reactivity
      was found with a plant chorismate synthase. However, in contrast to the plant
      enzyme, which is located to the plastid, P. falciparum chorismate synthase is
      found in the parasite cytosol, akin to the fungal enzymes that possess an
      intrinsic flavin reductase activity (i.e. are bifunctional). Thus, P. falciparum
      chorismate synthase has a combination of properties that distinguishes it from
      other described chorismate synthases.

PMID- 11298277
TI  - Pore-forming activity of type III system-secreted proteins leads to oncosis of
      Pseudomonas aeruginosa-infected macrophages.
AB  - The Pseudomonas aeruginosa cystic fibrosis isolate CHA induces type III secretion
      system-dependent but ExoU-independent oncosis of neutrophils and macrophages.
      Time-lapse microscopy of the infection process revealed the rapid accumulation of
      motile bacteria around infected cells undergoing the process of oncosis, a
      phenomenon we termed pack swarming. Characterization of the non-chemotactic
      CHAcheZ mutant showed that pack swarming is a bacterial chemotactic response to
      infected macrophages. A non-cytotoxic mutant, lacking the type III-secreted
      proteins PcrV, PopB and PopD, was able to pack swarm only in the presence of the
      parental strain CHA or when macrophages were pretreated with the pore-forming
      toxin streptolysin O. Interaction of P. aeruginosa with red blood cells (RBCs)
      showed that the contact-dependent haemolysis provoked by CHA requires secretion
      via the type III system and the PcrV, PopB/PopD proteins. The pore inserted into
      RBC membrane was estimated from osmoprotection experiments to be between 2.8 and
      3.5 nm. CHA-infected macrophages could be protected from cell lysis with PEG3350,
      indicating that the pore introduced into RBC and macrophage membranes is of
      similar size. The time course uptake of the vital fluorescent dye, Yo-Pro-1, into
      infected macrophages confirmed that the formation of transmembrane pores by CHA
      precedes cellular oncosis. Therefore, CHA-induced macrophage death results from a
      pore-forming activity that is dependent on the intact pcrGVHpopBD operon.

PMID- 11298278
TI  - Site-directed mutagenesis of intimin alpha modulates intimin-mediated tissue
      tropism and host specificity.
AB  - The hallmark of enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) Escherchia
      coli adhesion to host cells is intimate attachment leading to the formation of
      distinctive 'attaching and effacing' lesions. This event is mediated, in part, by
      binding of the bacterial adhesion molecule intimin to a second bacterial protein,
      Tir, delivered by a type III secretion system into the host cell plasma membrane.
      The receptor-binding activity of intimin is localized to the C-terminal 280 amino
      acids (Int280) and at least five distinct intimin types (alpha, beta, gamma,
      delta and epsilon) have been identified thus far. In addition to binding to Tir,
      intimin can also bind to a component encoded by the host. The consequence of
      latter intimin-binding activity may determine tissue tropism and host
      specificity. In this study we selected three amino acids in intimin, which are
      implicated in Tir binding, for site-directed mutagenesis. We used the yeast two
      hybrid system and gel overlays to study intimin-Tir protein interaction. In
      addition, the biological consequences of the mutagenesis was tested using a
      number of infection models (cultured epithelial cells, human intestinal explants
      and a mouse model). We report that while an I237/897A substitution (positions
      numbered according to Int280alpha/whole intimin alpha) in intimin alpha did not
      have any affect on its biological activity, a T255/914A substitution attenuated
      intimin activity in vivo. In contrast, the mutation V252/911A affected tissue
      targeting in the human intestinal explant model and attenuated the biological
      activity of intimin in the mouse model. This study provides the first clues of
      the molecular basis of how intimin mediates tissue tropism and host specificity.

PMID- 11298279
TI  - The role played by the group A streptococcal negative regulator Nra on bacterial
      interactions with epithelial cells.
AB  - Group A streptococci (GAS) specifically attach to and internalize into human
      epithelial host cells. In some GAS isolates, fibronectin-binding proteins were
      identified as being responsible for these virulence traits. In the present study,
      the previously identified global negative regulator Nra was shown to control the
      binding of soluble fibronectin probably via regulation of protein F2 and/or SfbII
      expression in the serotype M49 strain 591. According to results from a
      conventional invasion assay based on the recovery of viable intracellular
      bacteria, the increased fibronectin binding did not affect bacterial adherence to
      HEp-2 epithelial cells, but was associated with a reduction in the
      internalization rates. However, when examined by confocal and electron microscopy
      techniques, the nra-mutant bacteria were shown to exhibit higher adherence and
      internalization rates than the corresponding wild type. The mutant bacteria
      escaped from the phagocytic vacuoles much faster, promoting consistent
      morphological changes which resulted in severe host cell damage. The apoptotic
      and lytic processes observed in nra-mutant infected host cells were correlated
      with an increased expression of the genes encoding superantigen SpeA, the
      cysteine protease SpeB, and streptolysin S in the nra-mutant bacteria. Adherence
      and internalization rates of a nra/speB-double mutant at wild-type levels
      indicated that the altered speB expression in the nra mutant contributed to the
      observed changes in both processes. The Nra-dependent effects on bacterial
      virulence were confined to infections carried out with stationary growth phase
      bacteria. In conclusion, the obtained results demonstrated that the global GAS
      regulator Nra modulates virulence genes, which are involved in host cell damage.
      Thus, by helping to achieve a critical balance of virulence factor expression
      that avoids the injury of target cells, Nra may facilitate GAS persistence in a
      safe intracellular niche.

PMID- 11298280
TI  - Cytological and biochemical characterization of the FtsA cell division protein of
      Bacillus subtilis.
AB  - The actin-like protein FtsA is present in many eubacteria, and genetic
      experiments have shown that it plays an important, sometimes essential, role in
      cell division. Here, we show that Bacillus subtilis FtsA is targeted to division
      sites in both vegetative and sporulating cells. As in other organisms FtsA is
      probably recruited immediately after FtsZ. In sporulating cells of B. subtilis
      FtsZ is recruited to potential division sites at both poles of the cell, but
      asymmetric division occurs at only one pole. We have now found that FtsA is
      recruited to only one cell pole, suggesting that it may play an important role in
      the generation of asymmetry in this system. FtsA is present in much higher
      quantities in B. subtilis than in Escherichia coli, with approximately one
      molecule of FtsA for five of FtsZ. This means that there is sufficient FtsA to
      form a complete circumferential ring at the division site. Therefore, FtsA may
      have a direct structural role in cell division. We have purified FtsA and shown
      that it behaves as a dimer and that it has both ATP-binding and ATP-hydrolysis
      activities. This suggests that ATP hydrolysis by FtsA is required, together with
      GTP hydrolysis by FtsZ, for cell division in B. subtilis (and possibly in most
      eubacteria).

PMID- 11298281
TI  - Pph1 from Myxococcus xanthus is a protein phosphatase involved in vegetative
      growth and development.
AB  - Myxococcus xanthus is a Gram-negative bacterium with a complex life cycle that
      includes vegetative swarming on rich medium and, upon starvation, aggregation to
      form fruiting bodies containing spores. Both of these behaviours require multiple
      Ser/Thr protein kinases. In this paper, we report the first Ser/Thr protein
      phosphatase gene, pph1, from M. xanthus. DNA sequence analysis of pph1 indicates
      that it encodes a protein of 254 residues (Mr = 28 308) with strong homology to
      eukaryotic PP2C phosphatases and that it belongs to a new group of bacterial
      protein phosphatases that are distinct from bacterial PP2C phosphatases such as
      RsbU, RsbX and SpoIIE. Recombinant His-tagged Pph1 was purified from Escherichia
      coli and shown to have Mn2+ or Mg2+ dependent, okadaic acid-resistant phosphatase
      activity on a synthetic phosphorylated peptide, RRA(pT)VA, indicating that Pph1
      is a PP2C phosphatase. Pph1-expression was observed under both vegetative and
      developmental conditions, but peaked during early aggregation. A pph1 null mutant
      showed defects during late vegetative growth, swarming and glycerol spore
      formation. Under starvation-induced developmental conditions, the mutant showed
      reduced aggregation and failure to form fruiting bodies with viable spores. Using
      the yeast two-hybrid system, we have observed a strong interaction between Pph1
      and the M. xanthus protein kinase Pkn5, a negative effector of development. These
      results suggest a functional link between a Pkn2-type protein kinase and a PP2C
      phosphatase.

PMID- 11298282
TI  - Differential role of the Mu B protein in phage Mu integration vs. replication:
      mechanistic insights into two transposition pathways.
AB  - The Mu B protein is an ATP-dependent DNA-binding protein and an allosteric
      activator of the Mu transposase. As a result of these activities, Mu B is
      instrumental in efficient transposition and target-site choice. We analysed in
      vivo the role of Mu B in the two different recombination reactions performed by
      phage Mu: non-replicative transposition, the pathway used during integration, and
      replicative transposition, the pathway used during lytic growth. Utilizing a
      sensitive PCR-based assay for Mu transposition, we found that Mu B is not
      required for integration, but enhances the rate and extent of the process.
      Furthermore, three different mutant versions of Mu B, Mu BC99Y, Mu BK106A, and Mu
      B1-294, stimulate integration to a similar level as the wild-type protein. In
      contrast, these mutant proteins fail to support Mu growth. This deficiency is
      attributable to a defect in formation of an essential intermediate for
      replicative transposition. Biochemical analysis of the Mu B mutant proteins
      reveals common features: the mutants retain the ability to stimulate transposase,
      but are defective in DNA binding and target DNA delivery. These data indicate
      that activation of transposase by Mu B is sufficient for robust non-replicative
      transposition. Efficient replicative transposition, however, demands that the Mu
      B protein not only activate transposase, but also bind and deliver the target
      DNA.

PMID- 11298283
TI  - C-signal: a cell surface-associated morphogen that induces and co-ordinates
      multicellular fruiting body morphogenesis and sporulation in Myxococcus xanthus.
AB  - In Myxococcus xanthus, morphogenesis of multicellular fruiting bodies and
      sporulation are co-ordinated temporally and spatially. csgA mutants fail to
      synthesize the cell surface-associated C-signal and are unable to aggregate and
      sporulate. We report that csgA encodes two proteins, a 25 kDa species
      corresponding to full-length CsgA protein and a 17 kDa species similar in size to
      C-factor protein, which has been shown previously to have C-signal activity. By
      systematically varying the accumulation of the csgA proteins, we show that
      overproduction of the csgA proteins results in premature aggregation and
      sporulation, uncoupling of the two events and the formation of small fruiting
      bodies, whereas reduced synthesis of the csgA proteins causes delayed
      aggregation, reduced sporulation and the formation of large fruiting bodies.
      These results show that C-signal induces aggregation as well as sporulation, and
      that an ordered increase in the level of C-signalling during development is
      essential for the spatial co-ordination of these events. The results support a
      quantitative model, in which aggregation and sporulation are induced at distinct
      threshold levels of C-signalling. In this model, the two events are temporally co
      ordinated by the regulated increase in C-signalling levels during development.
      The contact-dependent C-signal transmission mechanism allows the spatial co
      ordination of aggregation and sporulation by coupling cell position and
      signalling levels.

PMID- 11298284
TI  - Two-hybrid analysis of domain interactions involving NtrB and NtrC two-component
      regulators.
AB  - Signal transduction by two-component regulatory systems involves phosphorylation
      of the receiver domain of a response regulator by the transmitter domain of the
      cognate histidine kinase. In the NtrBC system, phosphorylation of NtrC by NtrB
      results in transcriptional activation of nitrogen-regulated genes. We have used
      the yeast two-hybrid system to probe interactions between domains of the NtrB and
      NtrC proteins from Klebsiella pneumoniae. We constructed fusions from each of a
      series of proteins or protein domains to the activation and the DNA-binding
      domains of GAL4 and analysed expression of GAL1:lacZ and GAL1:HIS3 reporters in
      yeast. The DNA-binding domain of NtrC and the so-called sensor domain of NtrB
      appeared to provide the major determinants for dimerization of the fusion
      proteins. A strong and specific interaction was also shown between NtrB and NtrC,
      localized to the HN region of the NtrB transmitter module and to the NtrC
      receiver domain, whereas other domains of these proteins do not appear to
      contribute to the recognition specificity. The results presented here indicate
      that communication between two-component partners also involves protein-protein
      interactions that can be detected in vivo, suggesting that the yeast two-hybrid
      system is a powerful genetic tool for identifying functional partners of
      prokaryotic signal transduction pathways.

PMID- 11298285
TI  - Acquirement of cold sensitivity by quadruple deletion of the cspA family and its
      suppression by PNPase S1 domain in Escherichia coli.
AB  - Escherichia coli contains a large CspA family, CspA to CspI. Here, we demonstrate
      that E. coli is highly protected against cold-shock stress, as these CspA
      homologues existed at approximately a total of two million molecules per cell at
      low temperature and growth defect was not observed until four csp genes (cspA,
      cspB, cspE and cspG) were deleted. The quadruple-deletion strain acquired cold
      sensitivity and formed filamentous cells at 15 degrees C although chromosomes
      were normally segregated. The cold-sensitivity and filamentation phenotypes were
      suppressed by all members of the CspA family except for CspD, which causes
      lethality upon overexpression. Interestingly, the cold sensitivity of the mutant
      was also suppressed by the S1 domain of polynucleotide phosphorylase (PNPase),
      which also folds into a beta-barrel structure similar to that of CspA. The
      present results show that cold-shock proteins and S1 domains share not only the
      tertiary structural similarity but also common functional properties, suggesting
      that these seemingly distinct protein categories may have evolved from a common
      primordial RNA-binding protein.

PMID- 11298286
TI  - First evidence for gene replacement in Leptospira spp. Inactivation of L. biflexa
      flaB results in non-motile mutants deficient in endoflagella.
AB  - Leptospira spp. offer many advantages as model bacteria for the study of
      spirochaetes. However, homologous recombination between introduced DNA and the
      corresponding chromosomal loci has never been demonstrated. A unique feature of
      spirochaetes is the presence of endoflagella between the outer membrane sheath
      and the cell cylinder. We chose the flaB flagellin gene, constituting the
      flagellar core, as a target for gene inactivation in the saprophyte Leptospira
      biflexa. The amino acid sequence of the FlaB protein of L. biflexa was most
      similar to those of spirochaetes Brachyspira hyodysenteriae (agent of swine
      dysentery), Leptospira interrogans (agent of leptospirosis) and Treponema
      pallidum (agent of syphilis). A suicide vector containing the L. biflexa flaB
      gene disrupted by a kanamycin marker was UV irradiated or alkali denatured before
      electroporation. This methodology allowed the selection of many kanamycin
      resistant colonies resulting from single and double cross-over events at the flaB
      locus. The double recombinant mutants are non-motile, as visualized in both
      liquid and semi-solid media. In addition, a flaB mutant selected for further
      analysis was shown to be deficient in endoflagella by electron microscopy.
      However, most of the transformants had resulted from a single homologous
      recombination event, giving rise to the integration of the suicide vector. We
      evaluated the effect of the sacB and rpsL genes in L. biflexa as potential
      counterselectable markers for allelic exchange, and then used the rpsL system for
      the positive selection of flaB double recombinants in a streptomycin-resistant
      strain. Like the flaB mutant studied above, the Strr double cross-over mutant was
      non-motile and deficient in endoflagella. Our results demonstrate that FlaB is
      involved in flagella assembly and motility. They also show the feasibility of
      performing allelic replacement in Leptospira spp. by homologous recombination.

PMID- 11298287
TI  - The Cryptococcus neoformans STE11alpha gene is similar to other fungal mitogen
      activated protein kinase kinase kinase (MAPKKK) genes but is mating type
      specific.
AB  - Partial sequence analysis of the Cryptococcus neoformans MATalpha mating type
      locus revealed the presence of a gene with substantial sequence similarity to
      other fungal mitogen-activated protein (MAP) kinase kinase kinase (MAPKKK) genes.
      The C. neoformans gene, designated STE11alpha, showed the highest degree of
      similarity to the Neurospora crassa nrc-1, Schizosaccharomyces pombe byr2 and
      Saccharomyces cerevisiae STE11 genes. A polymerase chain reaction-mediated sib
      selection technique was successfully adapted for the purpose of disrupting
      STE11alpha. C. neoformans ste11alphaDelta mutants were found to be sterile,
      consistent with the phenotypes of ste11 and byr2 mutants in S. cerevisiae and S.
      pombe respectively. Haploid ste11alphaDelta mutants were also found to be unable
      to produce hyphae, suggesting that the C. neoformans gene is functionally
      conserved when compared with its S. cerevisiae MAPKKK counterpart. Comparison of
      the wild-type STE11alpha strain with a ste11alphaDelta disruptant for virulence
      using the mouse model showed that the ste11alphaDelta strain was less virulent,
      but the difference was only minor. In spite of some of the conserved functions of
      STE11alpha, linkage analysis showed that STE11alpha is only found in mating type
      alpha strains. These results demonstrate that, although functionally conserved,
      the mating pathway in C. neoformans has a unique organization.

PMID- 11298288
TI  - Transposon mutagenesis of Campylobacter jejuni identifies a bipartite energy
      taxis system required for motility.
AB  - Campylobacter jejuni constitutes the leading cause of bacterial gastroenteritis
      in the United States and a major cause of diarrhoea worldwide. Little is known
      about virulence mechanisms in this organism because of the scarcity of suitable
      genetic tools. We have developed an efficient system of in vitro transposon
      mutagenesis using a mariner-based transposon and purified mariner transposase.
      Through in vitro transposition of C. jejuni chromosomal DNA followed by natural
      transformation of the transposed DNA, large random transposon mutant libraries
      consisting of approximately 16 000 individual mutants were generated. The first
      genetic screen of C. jejuni using a transposon-generated mutant library
      identified 28 mutants defective for flagellar motility, one of the few known
      virulence determinants of this pathogen. We developed a second genetic system,
      which allows for the construction of defined chromosomal deletions in C. jejuni,
      and demonstrated the requirement of sigma28 and sigma54 for motility. In
      addition, we show that sigma28 is involved in the transcription of flaA and that
      sigma54 is required for transcription of three other flagellar genes, flaB and
      flgDE. We also identified two previously uncharacterized genes required for
      motility encoding proteins that we call CetA and CetB, which mediate energy taxis
      responses. Through our analysis of the Cet proteins, we propose a unique
      mechanism for sensing energy levels and mediating energy taxis in C. jejuni.

PMID- 11298289
TI  - Cell cycle regulation in the hyperthermophilic crenarchaeon Sulfolobus
      acidocaldarius.
AB  - The regulation and co-ordination of the cell cycle of the hyperthermophilic
      crenarchaeon Sulfolobus acidocaldarius was investigated with antibiotics. We
      provide evidence for a core regulation involving alternating rounds of chromosome
      replication and genome segregation. In contrast, multiple rounds of replication
      of the chromosome could occur in the absence of an intervening cell division
      event. Inhibition of the elongation stage of chromosome replication resulted in
      cell division arrest, indicating that pathways similar to checkpoint mechanisms
      in eukaryotes, and the SOS system of bacteria, also exist in archaea. Several
      antibiotics induced cell cycle arrest in the G2 stage. Analysis of the run-out
      kinetics of chromosome replication during the treatments allowed estimation of
      the minimal rate of replication fork movement in vivo to 250 bp s-1. An efficient
      method for the production of synchronized Sulfolobus populations by transient
      daunomycin treatment is presented, providing opportunities for studies of cell
      cycle-specific events. Possible targets for the antibiotics are discussed,
      including topoisomerases and protein glycosylation.

PMID- 11298290
TI  - Cold-regulated genes under control of the cold sensor Hik33 in Synechocystis.
AB  - A histidine kinase, Hik33, appears to sense decreases in temperature and to
      regulate the expression of certain cold-inducible genes in the cyanobacterium
      Synechocystis sp. PCC6803. To examine the role of Hik33 in the regulation of gene
      expression, we analysed a DeltaHik33 mutant using the DNA microarray technique.
      In wild-type cells, genes that were strongly induced at low temperature encoded
      proteins that were predominantly subunits of the transcriptional and
      translational machinery. Most cold-repressible genes encoded components of the
      photosynthetic machinery. Mutation of the hik33 gene suppressed the expression of
      some of these cold-regulated genes, which could be divided into three groups
      according to the effect of the mutation of hik33. In the first group, regulation
      of gene expression by low temperature was totally abolished; in the second group,
      the extent of such regulation was reduced by half; and, in the third group, such
      regulation was totally unaffected. These results suggest that expression of the
      genes in the first group is regulated solely by Hik33, expression of genes in the
      third group is regulated by an as yet unidentified cold sensor, and expression of
      genes in the second group is regulated by both these cold sensors.

PMID- 11298292
TI  - BldD is a direct regulator of key developmental genes in Streptomyces coelicolor
      A3(2).
AB  - BldD is a transcription factor required for aerial hyphae formation in the
      filamentous bacterium Streptomyces coelicolor. Three targets of BldD regulation
      were discovered by a number of means, including examination of bld gene
      interdependence, selective enrichment of chromosomal DNA fragments bound by BldD
      and searching the promoter regions of known developmental genes for matches to a
      previously characterized BldD binding site. The three BldD targets identified
      were the developmental sigma factor genes, whiG and bldN, and a previously
      uncharacterized gene, designated bdtA, encoding a putative transcription factor.
      In each target gene, the sequences bound by BldD were characterized by
      electrophoretic mobility shift and DNase I footprinting assays, and their
      alignment suggested AGTgA (n)m TCACc as a consensus BldD operator. The in vivo
      effect of mutation in bldD on the expression of these three target genes was
      assessed using S1 nuclease protection assays. In each case, target gene
      expression was upregulated during early colony development in the bldD
      background, suggesting that, in the wild type, BldD acts to repress premature
      expression of whiG, bldN and bdtA during vegetative growth.

PMID- 11298291
TI  - Positive regulation of motility and flhDC expression by the RNA-binding protein
      CsrA of Escherichia coli.
AB  - Many species of bacteria devote considerable metabolic resources and genetic
      information to the ability to sense the environment and move towards or away from
      specific stimuli using flagella. In Escherichia coli and related species,
      motility is regulated by several global regulatory circuits, which converge to
      modulate the overall expression of the master operon for flagellum biosynthesis,
      flhDC. We now show that the global regulator CsrA of E. coli K-12 is necessary
      for motility under a variety of growth conditions, as a result of its role as an
      activator of flhDC expression. A chromosomally encoded flhDC'-'lacZ translational
      fusion was expressed at three- to fourfold higher levels in csrA wild-type
      strains than in isogenic csrA mutants. Purified recombinant CsrA protein
      stimulated the coupled transcription-translation of flhDC'-' lacZ in S-30
      extracts and bound to the 5' segment of flhDC mRNA in RNA mobility shift assays.
      The steady-state level of flhDC mRNA was higher and its half-life was
      approximately threefold greater in a csrA wild-type versus a csrA mutant strain.
      Thus, CsrA stimulates flhDC gene expression by a post-transcriptional mechanism
      reminiscent of its function in the repression of glycogen biosynthesis.

PMID- 11298293
TI  - Transforming growth factor-beta suppresses interferon-gamma-induced
      toxoplasmastatic activity in murine macrophages by inhibition of tumour necrosis
      factor-alpha production.
AB  - Activation of macrophages plays an important role in the host resistance against
      intracellular pathogens. Various mechanisms are employed to control the
      activation processes and limit tissue damage by factors produced by activated
      macrophages. One of these mechanisms is the production of macrophage-deactivating
      cytokines, such as tumour growth factor (TGF)-beta. The present study concerns
      the effects of TGF-beta on interferon (IFN)-gamma-induced activation of murine
      macrophages with respect to induction of toxoplasmastatic activity, and
      production of tumour necrosis factor (TNF)-alpha, prostaglandin E2 (PGE2) and
      reactive nitrogen intermediates (RNI). IFN-gamma activation of macrophages
      resulted in inhibition of T. gondii proliferation [mean fold increase (FI) = 1.8,
      control mean FI = 7.0]; polymyxin B had no effect on this activation. The IFN
      gamma-induced toxoplasmastatic activity of macrophages was inhibited by TGF-beta
      (mean FI = 6.3), which was also found for the IFN-gamma-induced production of TNF
      alpha, RNI and PGE2 by macrophages. We found that PGE2, which has macrophage
      deactivating properties, was not involved in the inhibition of macrophage
      activation by TGF-beta. The deactivating activities of TGF-beta on the IFN-gamma
      induced toxoplasmastatic activity and production of RNI are mediated by
      inhibition of production of TNF-alpha. Addition of exogenous TNF-alpha during the
      incubation of macrophages with IFN-gamma and TGF-beta abrogated the deactivating
      activity of TGF-beta. In sum, the results demonstrate that inhibition of TNF
      alpha production is a key factor in the TGF-beta-induced suppression of
      macrophage activation with respect to toxoplasmastatic activity and RNI
      production.

PMID- 11298294
TI  - Leishmania donovani-induced macrophages cyclooxygenase-2 and prostaglandin E2
      synthesis.
AB  - Prostaglandin E2 (PGE2) secretion during Leishmania infection has been reported.
      However, the signalling mechanisms mediating this response are not well
      understood. Since cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2)
      are involved in PGE2 synthesis in response to various stimuli, the implication of
      these enzymes was evaluated in Leishmania-infected phorbol myristate acetate
      differentiated U937 human monocytic cell line. Time-course experiments showed
      that PGE2 synthesis increased significantly in parallel with COX-2 expression
      when cells were incubated in the presence of Leishmania donovani promastigotes or
      lipopolysaccharides (LPS). Increase in cPLA2 mRNA expression was only detected
      when cells were stimulated with LPS. Indomethacin, genistein, and H7, which are
      antagonists of COX-2, protein tyrosine kinase (PTK) and protein kinase C (PKC),
      respectively, inhibited PGE2 production induced by L. donovani and LPS. However,
      only H7 inhibited COX-2 mRNA synthesis, and there was a significant correlation
      between PGE2 inhibition and reduced COX-2 expression. Collectively, our results
      indicate that infection of U937 by L. donovani leads to the generation of PGE2 in
      part through a PKC-dependent signalling pathway involving COX-2 expression. They
      further reveal that PTK-dependent events are necessary for Leishmania-induced
      PGE2 generation, but not for COX-2 expression. A better understanding of the
      mechanisms by which Leishmania can induce PGE2 production could provide insight
      into the pathophysiology of leishmaniasis and may help to improve therapeutic
      approaches.

PMID- 11298295
TI  - Regional immune responses with stage-specific antigen recognition profiles
      develop in lymph nodes of pigs following Ascaris suum larval migration.
AB  - The early life-cycle of the pig round worm, Ascaris suum, involves well-defined
      larval development in the liver, lungs and finally the small intestine. Distinct
      regional immune responses to larval antigens of A. suum were observed in the
      draining lymph nodes of immunized and challenged pigs during larval migration.
      This was reflected in a transient enlargement of the stimulated lymph nodes, due
      to increases in numbers of B cells and CD4 T cells, and the production of A. suum
      specific antibody by antibody secreting cell (ASC) cultures. Larval antigen
      recognition pattern of antibodies in serum, bile and draining lymph node ASC
      culture supernatant (ASC-probes) was examined by immunoblotting. This revealed
      distinct organ-specific recognition patterns of larval-specific antigens by the
      draining lymph nodes at different times after challenge. In particular, an early
      larval 42 kDa antigen was recognized specifically by ASC-probes of the liver
      lymph nodes at 7 but not 14 days postchallenge (pc) which was not detected in
      other lymph nodes, serum or bile of the same pig. Similarly, a late larval
      antigen of 34 kDa was uniquely detected by lung and jejunal ASC-probes at 14 days
      pc. These observations demonstrate how development of distinct regional immune
      responses in tissues with different antigen stimulation can be monitored with ASC
      probes and flow cytometry.

PMID- 11298296
TI  - Dendritic cells pulsed with unfractionated helminthic proteins to generate
      antiparasitic cytotoxic T lymphocyte.
AB  - Dendritic cells (DC) are sentinels of immunity. We determined their role in the
      induction of immunity against alveolar echinococcosis, caused by the larval stage
      of the cestode Echinococcus multilocularis. Furthermore, we evaluated if
      unfractionated protein from E. multilocularis (Em-Ag) can be used as loading
      agent for DC (comparable to unfractionated tumour proteins) in order to generate
      antiparasitic cytotoxic T lymphocyte (CTL). Interestingly, immature DC did not
      mature in the presence of 1 microg/ml Em-Ag as analysed by FACS and mixed
      leucocyte reactions. Yet, their capacity to take up dextran was markedly reduced.
      Further maturation of immature Em-Ag pulsed DC could be induced by
      proinflammatory cytokines. These mature DC were slightly better inducers of T
      cell proliferation when compared with unpulsed mature DC. Importantly, by
      repetetive stimulation of autologous CD8+ lymphocytes with the Em-Ag pulsed
      mature DC, we were able to generate specifically proliferating CTL lines. Thus,
      immunotherapy with ex vivo generated Em-Ag pulsed DC might be of benefit for
      patients inheriting this incurable disease.

PMID- 11298297
TI  - Cross-protection studies with gut membrane glycoprotein antigens from Haemonchus
      contortus and Teladorsagia circumcincta.
AB  - Gel profiles of the peanut and ConA lectin binding integral membrane
      glycoproteins of Teladorsagia circumcincta and Haemonchus contortus were compared
      and found to be considerably different. However, some of the Teladorsagia
      polypeptides were recognized by antisera specific for Haemonchus amino-, metallo-
      or aspartyl peptidases, enzymes which are known to be protective antigens for
      that parasite. As expected, an experimental vaccine containing these Haemonchus
      proteases was extremely effective against homologous challenge, reducing egg and
      worm counts by more than 99% and 92%, respectively, but it did not provide any
      useful cross-protection against either T. circumcincta, Trichostrongylus axei or
      Cooperiaoncophora. A reciprocal experiment, where sheep were immunized with the
      equivalent glycoproteins from T. circumcincta, showed that, while they were not
      protected against homologous challenge, there was some cross-protection against
      Haemonchus as measured by a significant reduction in worm egg output.

PMID- 11298299
TI  - Early treatment and evidence-based orthodontics. Early treatment symposium.

PMID- 11298298
TI  - The 14-3-3 protein as a vaccine candidate against schistosomiasis.
AB  - We have previously reported on the cloning of the 14-3-3 protein of Schistosoma
      mansoni. Here, we evaluate the potential use of this protein as a vaccine
      candidate against infection by S. mansoni. Sm14-3-3 was expressed and purified
      either as a free protein or as a fusion protein to SjGST or MBP. Sera from mice
      infected with S. mansoni recognized both SjGST and 14-3-3, indicating that
      antibodies against these two proteins are induced in the course of the natural
      infection. Furthermore, mice immunized with either 14-3-3, GST or 14-3-3-GST,
      reacted with cercaria lysate. A cellular immune response was also detected,
      particularly in mice immunized with 14-3-3-GST. With respect to the effect on
      biological functions, antibodies to 14-3-3 and 14-3-3-GST caused 23-32%
      complement-mediated cytotoxcity of S. mansoni schistosomula compared to only 10
      11% induced by either normal mouse serum, or GST alone. In challenge infection
      with S. mansoni, immunization with 14-3-3, either as a fusion protein or as a
      free protein, led to protection ranging from 25-46%, as determined by reduction
      of adult worm burden, while SjGST alone elicited only 0-8% protection and MBP
      alone did not elicit any protection.

PMID- 11298300
TI  - Early treatment and evidence-based orthodontics. Timing of treatment.

PMID- 11298301
TI  - Early treatment and evidence-based orthodontics. Early treatment.

PMID- 11298302
TI  - Evidence-based orthodontics and functional appliances.

PMID- 11298303
TI  - Evidence-based orthodontics in Southeast Asia.

PMID- 11298304
TI  - Comments on evidence-based teaching.

PMID- 11298305
TI  - Interdisciplinary care leads the way.

PMID- 11298306
TI  - Autotransplantation of teeth in orthodontic treatment.

PMID- 11298307
TI  - Eruption pattern of autotransplanted premolars visualized by radiographic color
      coding.
AB  - Eruption patterns and root growth were visualized with the use of a new
      technique, radiographic color-coding, for comparison of the development of
      autotransplanted premolars with contralateral control teeth. Rates of eruption
      and root growth were studied. The eruption pattern and rate was assessed relative
      to the first molar. Maximum rates were found to occur between 30 and 60 days
      after transplantation. There were no significant differences between transplants
      and their contralaterals. Two distinct categories of eruption patterns were
      demonstrated. One group showed a tendency toward an initial rate of transplant
      eruption that was somewhat faster than that of the contralaterals. The other
      group showed initially retarded eruption. Possible explanations were discussed.
      Because no significant differences between the transplants and the contralaterals
      were observed, it was concluded that autotransplantation is a sound treatment
      option for substitution of missing teeth, at least from a tooth development point
      of view.

PMID- 11298308
TI  - Revascularization after cryopreservation and autotransplantation of immature and
      mature apicoectomized teeth.
AB  - Autotransplantation of immature teeth can have a success rate of almost 98% if
      the tooth is atraumatically transplanted from the donor site to a suitable
      acceptor site and the extraoral time is kept to a minimum. When the tooth cannot
      be transplanted immediately, cryopreservation and storage in a tooth bank offer
      new possibilities for autotransplantation. However, the effect of
      cryopreservation on the revascularization of transplanted teeth is still unknown.
      The purpose of this study was to examine revascularization in immature teeth that
      have an open apex and in mature teeth that have had the apex cut. The study was
      carried out on 16 teeth in 2 dogs; 8 teeth were removed and immediately
      transplanted to the contralateral position and 8 teeth were cryopreserved and
      transplanted 1 week later. The results show that: (1) teeth can revascularize
      after autotransplantation if the original pulp tissue is removed at the time of
      extraction, (2) there is no significant difference in the amount of
      revascularization between teeth stored in a tooth bank for 7 days and those
      immediately transplanted without freezing, and (3) there is no difference in the
      ingrowth of new pulpal tissue between mature apicoectomized teeth and immature
      teeth.

PMID- 11298309
TI  - Soft tissue profile changes following mandibular advancement surgery:
      predictability and long-term outcome.
AB  - The objectives of this cephalometric study were to assess long-term changes in
      the soft tissue profile following mandibular advancement surgery and to
      investigate the relationship between soft tissue and hard tissue movements. The
      sample consisted of 61 patients treated consecutively for mandibular
      retrognathism with orthodontic therapy combined with bilateral sagittal split
      osteotomy and rigid fixation. Lateral cephalograms were taken on 6 occasions:
      immediately before surgery, immediately after surgery, 2 and 6 months after
      surgery, and 1 and 3 years after surgery. Postsurgical changes in the upper and
      the lower lips and the mentolabial fold were more pronounced among low-angle
      cases compared with high-angle cases. In accordance with other studies, the soft
      tissue chin and the mentolabial fold were generally found to follow their
      underlying skeletal structures in a 1:1 ratio. Because of the strong influence
      skeletal relapse has on soft tissue profile changes, alternative ratios of soft
      tissue-to-hard tissue movement that accounted for mean relapse were also
      generated. It is suggested that if a more realistic long-term prediction of the
      postsurgical soft tissue profile is desirable, then ratios incorporating mean
      relapse should be used rather than estimates based on a 1:1 relationship.

PMID- 11298310
TI  - Mandibular advancement surgery in high-angle and low-angle class II patients:
      different long-term skeletal responses.
AB  - The objective of this cephalometric study was to compare skeletal stability and
      the time course of postoperative changes in high-angle and low-angle Class II
      patients after mandibular advancement surgery. The subjects were 61 consecutive
      mandibular retrognathism patients whose treatment included bilateral sagittal
      split osteotomy and rigid fixation. The patients were divided according to the
      preoperative mandibular plane angle; the 20 patients with the lowest mandibular
      plane angle (20.8 degrees +/- 4.9 degrees ) constituted the low-angle group,
      while the 20 cases with the highest mandibular plane angle (43.0 degrees +/- 4.0
      degrees ) represented the high-angle group. Lateral cephalograms were taken on 6
      occasions: immediately before surgery, immediately after surgery, 2 and 6 months
      after surgery, and 1 and 3 years after surgery. Results demonstrated that the
      high-angle and low-angle groups had different patterns of surgical and
      postoperative changes. High-angle patients were associated with both a higher
      frequency and a greater magnitude of horizontal relapse. While 95% of the total
      relapse took place during the first 2 months after surgery in the low-angle
      group, high-angle patients demonstrated a more continuous relapse pattern, with a
      significant proportion (38%) occurring late in the follow-up period. Possible
      reasons for the different postsurgical response are discussed.

PMID- 11298311
TI  - Positional change of the hyoid bone after bilateral sagittal split osteotomy with
      rigid and wire fixation.
AB  - The purpose of this study was to compare positional changes of the hyoid bone and
      the amount of postsurgical compensation in mandibular position in patients who
      received either wire or rigid fixation after surgery. Data were analyzed from 97
      patients (25 males and 72 females) who were randomized to receive wire (43) or
      rigid (54) fixation after mandibular advancement surgery as part of a multicenter
      clinical trial. Radiographs were digitized before surgery (T2), immediately after
      surgery (T3), and 8 weeks (T4), 6 months (T5), 1 year (T6), and 2 years (T7)
      after surgery. The wire group had greater sagittal relapse of the hyoid bone at
      T6 (P =.007), which persisted at T7 (P =.02). Both groups showed upward movement
      of the hyoid bone after surgery. There was no relationship between the vertical
      change in the the hyoid bone position and the vertical position of mandible (B
      point y coordinate, mandibular plane). However, there was a relationship between
      the horizontal hyoid bone position and B point during the postsurgical period
      (rigid, r = 0.450; wire, r = 0.517). The direct distance from the hyoid bone to
      basion increased (P <.001) in both groups at T3 and then recovered its original
      length after 8 weeks (P <.001). The rigid group showed no significant change in
      distance from the hyoid to the genial tubercles, but the wire group showed
      recovery of the muscle length at T6 (P <.05) and T7 (P <.05).

PMID- 11298312
TI  - Osteogenesis in the glenoid fossa in response to mandibular advancement.
AB  - The purpose of this study was to identify the temporal sequence of cellular
      changes in the glenoid fossa and to quantify the amount of bone formation in
      response to mandibular advancement. One hundred 35-day-old female Sprague-Dawley
      rats were randomly divided into 5 experimental groups (15 rats each) and 5
      control groups (5 rats each). In the experimental groups, functional appliances
      were used to create continuous forward mandibular advancement. The rats were
      killed after 3, 7, 14, 21, and 30 days. Sections were cut through the glenoid
      fossa in the parasagittal plane and stained with periodic acid and Schiff's
      reagent for evaluation of bone formation and with hematoxylin and eosin for
      observation of cellular response. The results showed that, in the control rats,
      bone formation was initially higher in the posterior and middle regions than in
      the anterior region then decreased over time in all regions. In the experimental
      group, bone formation significantly increased from day 7 to day 30 compared with
      control rats. Day 21 marked the highest levels of bone formation in the middle
      (+184%) and posterior regions (+300%). Mandibular protrusion resulted in the
      osteoprogenitor cells being oriented in the direction of the pull of the
      posterior fibers of the disc and also resulted in a considerable increase in bone
      formation in the glenoid fossa.

PMID- 11298313
TI  - A comparison of cranial base growth in Class I and Class II skeletal patterns.
AB  - The purpose of this retrospective longitudinal study was to compare 7
      cephalometric measurements of the cranial base in subjects with Class I and Class
      II skeletal patterns at ages 1 month, 2 years, and 14 years. A sample of 22 Class
      I and 21 Class II subjects was selected; the inclusion criteria were overjet,
      ANB, and Harvold unit difference. Analyses of head circumference, crown-rump
      length, and weight revealed no significant (P >.15) differences between the Class
      I and Class II infant subjects at the initial age (1 month). One angular and 6
      linear measurements were first compared with a multivariate analysis of variance,
      which revealed significant effects for age (P <.0001) and the age by skeletal
      pattern interaction (P =.0266) but not for skeletal pattern (P =.3705). Analyses
      of variance showed significant (P <.0001) age effects for each of the
      cephalometric variables but no significant skeletal pattern effects (P >.10). The
      anterior cranial base measurement of nasion to sphenoethmoidal suture was the
      only variable found to have a significant age by skeletal pattern interaction (P
      <.006), which revealed a difference in the timing of its growth spurt that
      occurred between 1 month and 2 years in the Class I subjects and between 2 years
      and 14 years in the Class II subjects. There were no significant differences
      between the skeletal classes at any of the 3 ages evaluated. Conclusions from
      this study indicate that cranial base growth patterns are similar for Class I and
      Class II subjects and that the premise of a more obtuse "saddle angle" or cranial
      base angle in Class II skeletal patterns was not supported.

PMID- 11298314
TI  - Three-dimensional evaluation of skeletal and dental asymmetries in Class II
      subdivision malocclusions.
AB  - The objective of this study was to determine if any significant differences
      existed with regard to dental and skeletal asymmetries between subjects with
      Angle Class II subdivision malocclusions and subjects with normal occlusions. The
      sample consisted of 30 subjects in each of the 2 groups. Each possessed a full
      complement of permanent teeth, including first molars. The average age of
      subjects was 15.76 years in the Class II subdivision group and 22.42 years in the
      normal occlusion group. Measurements were obtained with the use of
      submentovertex, posteroanterior, and corrected oblique cephalometric radiographs.
      In the submentovertex radiographs, symmetry was assessed by measuring the
      relative differences in the spatial positions of dental and skeletal landmarks
      between the right and the left sides in both anteroposterior and transverse
      dimensions. Coordinate systems were used to represent the mandible, cranial
      floor, and the maxilla. In the posteroanterior radiographs, symmetry was assessed
      similarly by measuring the relative differences in the spatial positions of
      dental and skeletal landmarks between the right and the left sides. In the
      corrected oblique radiographs, symmetry was assessed by measuring the differences
      in size of dental and skeletal structures between the right and the left sides.
      Variables were analyzed with multivariate logistic regression analysis. The
      results demonstrated that the primary contributor to the differences between the
      2 groups was the distal positioning of the mandibular first molars on the Class
      II side in patients whose mandibles showed no unusual skeletal or positional
      asymmetries. A secondary contributor was the mesial positioning of the maxillary
      first molars on the Class II side. Furthermore, the posteroanterior radiographic
      analysis showed that the more frequent distal positioning of the mandibular
      molars on the Class II side, compared with the mesial positioning of the
      maxillary molars on that side resulted in mandibular dental midline deviation to
      the Class II side more frequently than the maxillary dental midline to the
      opposite side.

PMID- 11298315
TI  - Localization of mandibular changes in patients with class II division 1
      malocclusions treated with twin-block appliances: finite element scaling
      analysis.
AB  - Thirty mandibular landmarks were digitized from cephalographs of 46 children
      (prepubertal, approximately 10 years old) and 53 adolescents (pubertal,
      approximately 13 years old) to determine mandibular morphological changes in
      patients with Class II Division 1 malocclusions treated with Twin-block
      appliances. Procrustes superimposition computed average geometries and an
      analysis of variance were performed on the cephalographs. Prepubertal
      pretreatment and approximately 13-month-posttreatment profiles and pubertal
      pretreatment and approximately 22-month-posttreatment profiles were statistically
      different (P <.002). In male prepubertal configurations, a color-coded finite
      element scaling analysis revealed a conspicuous area of positive allometry (
      approximately 12%) in the condylar neck and negative allometry ( approximately
      17%) at the apex of the coronoid process. For the female prepubertal
      configuration, local increases in size were discernible in the condylar neck (
      approximately 3%) and in the apex of the coronoid process ( approximately 4%).
      Comparing male pubertal configurations, finite element scaling analysis revealed
      marked positive allometry ( approximately 27%) in the condylar neck and negative
      allometry ( approximately 16%) at the apex of the coronoid process. For the
      female pubertal configurations, local increases in size were noticeable at the
      condylar neck ( approximately 15%), with negative allometry ( approximately 9%)
      in the coronoid process. For shape change, all configurations were highly
      isotropic over the entire mandibular nodal mesh. Therefore, in growing patients
      treated for Class II Division 1 malocclusions with Twin-block appliances,
      condylar growth, coronoid process remodeling, and osteogenesis in corpus and
      dentoalveolar regions may reflect the correction of the underlying skeletal
      dysmorphology.

PMID- 11298316
TI  - The reliability of 3 sagittal reference planes in the assessment of Class I and
      Class III treatment.
AB  - The objective of this study was to test the reproducibility and validity of 3
      sagittal reference planes with the use of the Wits analysis. Measurements made to
      the functional occlusal plane, the bisected occlusal plane, and the
      maxillomandibular bisector were compared with each other and with the angular
      measurement of the ANB angle. The angular relationship of these reference planes
      to the postmaxillary vertical reference plane was also studied. The data were
      collected from pretreatment (T1), posttreatment (T2), and 2-year postretention
      (T3) lateral cephalograms of 35 Class I and 10 Class III subjects. Nonextraction
      treatment for these patients was performed with full fixed orthodontic appliances
      in the permanent dentition. Cephalometric data were compared with 39 Class I and
      9 Class III control subjects. The serial lateral cephalograms of untreated
      control subjects that were analyzed were taken at ages approximating those of the
      treated groups at T1, T2, and T3. The maxillomandibular bisector was determined
      to be an easily identifiable and reproducible reference plane that exhibited
      greater stability over time with both growth and treatment than either the
      functional occlusal plane or bisected occlusal plane. The mean values for the
      maxillomandibular bisector Wits result for Class I and III populations were
      distinct and, when combined with previous Class II data, yielded a triphasic
      distribution that may be a useful clinical tool for patient assessment.

PMID- 11298317
TI  - Changes in orofacial muscle activity in response to changes in respiratory
      resistance.
AB  - Increased resistance in the upper airway is known to be a contributing factor to
      deviant facial growth patterns. These patterns are the result of a prolonged
      presence of unbalanced oropharyngeal muscle activity. We hypothesized that
      mechanically increasing airway resistance would enhance the activity of the
      muscles facilitating respiration, and we attempted to demonstrate that the
      increased muscle activity is modulated by mechanoreceptors in the pharyngeal
      airway. The response of oropharyngeal muscles to increased airway resistance
      during spontaneous breathing was observed in 11 rabbits. Electromyographic
      signals from the ala nasi, orbicularis oris superior, genioglossus, mylohyoid
      muscles, and the diaphragm were recorded by fine-wire electrodes. Pressure
      changes were monitored by pressure transducers at the side branch of the cannule
      close to openings for the nose and the trachea. The study consisted of 2
      experimental sessions. First, to evoke the response of muscles to the inspiratory
      resistance, increasing stepwise polyethylene tubes of various diameters were
      attached to the nasal and tracheal opening and the diameter of the tubes was
      gradually reduced. Muscle activity changes in response to the increased
      resistance were recorded during spontaneous nasal or tracheal breathing. Second,
      to examine muscle responses to negative pressure to the pharyngeal airway,
      irrespective of breathing activity, the pharynx was isolated as a closed circuit
      by a stoma constructed at a more caudal side in the trachea. Muscle responses to
      the negative pressure generated by a syringe in the pharyngeal segment were
      measured. Nasal breathing induced a greater muscle activity than did tracheal
      breathing, in general, at P <.05. When resistance was gradually increased, nasal
      breathing resulted in a greater increase in muscle activity than did tracheal
      breathing (P <.05), except in the diaphragm. Application of negative pressure to
      the isolated pharyngeal airway segment increased the muscle activity
      significantly (P <.05). We conclude that an increased airway resistance may
      facilitate oropharyngeal muscle activity through mechanoreceptors in the
      oropharyngeal airway.

PMID- 11298319
TI  - ASP: an idea before its time--or is it time?

PMID- 11298320
TI  - Litigation, legislation, and ethics. Sticks and stones.

PMID- 11298318
TI  - Nickel-titanium mandibular bonded lingual 3-3 retainer: for permanent retention
      and solving relapse of mandibular anterior crowding.
AB  - An innovative technique that involves a nickel-titanium mandibular bonded lingual
      3-3 retainer was used to treat relapse of mandibular anterior crowding. The
      purpose of this study was to demonstrate clinical procedures and to study the
      effects of a new mandibular bonded lingual 3-3 retainer on the mandibular dental
      arch. In 18 patients, changes in the irregularity index and in arch dimensions
      (intercanine width, arch length, and arch depth) were measured against the
      patients' mandibular dental casts, which were obtained at completion of the
      previous orthodontic treatment (T(0)). These measurements were taken at the
      beginning of retreatment (T(1)), and 2 (T(2)), 4 (T(3)), and 6 (T(4)) months
      after initiation of retreatment. During the period of relapse (T(0)-T(1)), the
      irregularity index increased from 1.3 to 3.5 mm and the mandibular arch
      dimensions decreased. Four months after a segment of.018-in nickel-titanium
      archwire was bonded lingually from canine to canine, the irregularity index
      decreased from 3.5 to 1.0 mm and the arch dimensions increased and recovered
      their original posttreatment dimensions. The nickel-titanium archwire was left in
      place for permanent retention after the period of retreatment. This simple
      technique effectively solved relapse of mandibular anterior crowding in 4 months.
      This mandibular bonded lingual 3-3 retainer could be used both actively, to re
      treat mandibular anterior crowding without the use of lingual brackets, and
      passively, for maintenance as a bonded lingual retainer.

PMID- 11298321
TI  - Down-modulation of TCR/CD3 surface complexes after HIV-1 infection is associated
      with differential expression of the viral regulatory genes.
AB  - We have investigated the mechanism(s) involved in progressive abrogation of CD3
      gamma gene expression after HIV-1 or HIV-2 infection. A comparison of
      intracellular virus expression with T cell receptor surface density, revealed
      both high and low levels of viral p24 antigen in the TCR/CD3(hi), TCR/CD3(lo),
      and TCR/CD3(-) cells. Furthermore, in non-productively infected cells expressing
      the multiply spliced, virally encoded tat, rev, and nef regulatory gene
      transcripts, the same progressive loss of surface TCR/CD3 complexes was observed.
      We treated HIV-1-infected cells with antisense (AS) phosphorothioate
      oligodeoxynucleotides (P-OdN) targeted to the viral regulatory genes. All of the
      HIV-1 sequence-specific AS-P-OdN's inhibited intracellular p24 antigen expression
      in a time- and dose-dependent manner; although, blocking p24 expression alone was
      not sufficient to modulate TCR/CD3 surface density. Only Tat-AS and Nef-AS were
      able to delay TCR/CD3 down-modulation on receptor-positive cells or drive
      receptor up-regulation on receptor-negative cells. In contrast, Rev-AS
      accelerated TCR/CD3 loss on receptor-positive cells. RT-PCR revealed that Tat-AS
      and Nef-AS reduce the level of tat, nef, and rev transcripts, while Rev-AS
      increases the level of tat and nef transcripts in infected cells. Thus, when
      intracellular conditions favor expression of tat and/or nef in the absence of
      rev, CD3-gamma gene transcripts and TCR/CD3 surface density are down-modulated.

PMID- 11298322
TI  - An accessory role of TCRgammadelta (+) cells in the exacerbation of inflammatory
      bowel disease in TCRalpha mutant mice.
AB  - T cell receptor alpha mutant (TCRalpha (-/-)) mice, which spontaneously develop
      colitis under conventional conditions, did not show any signs of colitis under
      germ-free conditions, leaving TCRalpha (-)beta (+) cells (beta (dim) cells) and
      TCRgamma delta (+) cells much reduced. Moreover, TCRalpha (-/-) mice with
      alymphoplastic mutation (aly/aly TCRalpha (-/-) mice), which lack Peyer's patches
      and peripheral lymph nodes, did not suffer from colitis. While both beta (dim)
      cells and TCRgamma delta (+) cells were present in the colons of aly/aly TCRalpha
      (-/-) mice and aly/+ TCRalpha (-/-) mice, cytotoxicity of colonic TCRgamma delta
      (+) cells in aly/aly TCRalpha (-/-) mice was almost abolished. Transfer of
      TCRgamma delta (+) cells from TCRalpha (-/-) mice into scid/scid mice or aly/aly
      TCRalpha (-/-) mice could not induce colitis, but injection of anti-TCRdelta mAb
      into TCRalpha (-/-) mice prevented colitis from developing. Finally, TCRalpha (-/
      ) mice expressing transgenic (Tg) KN6-TCRgamma delta hardly developed colitis,
      accompanied by colonization of non-cytotoxic Tg TCRgamma delta (+) cells in their
      colonic mucosa. These results demonstrate that intestinal resident TCRgamma delta
      (+) cells may be involved in the exacerbation of inflammatory bowel disease in
      TCRalpha (-/-) mice.

PMID- 11298323
TI  - The clustered Fcgamma receptor II is recruited to Lyn-containing membrane domains
      and undergoes phosphorylation in a cholesterol-dependent manner.
AB  - Phosphorylation of clustered Fcgamma receptor II (FcgammaRII) by Src family
      tyrosine kinases is the earliest event in the receptor signaling cascade.
      However, the molecular mechanisms for the interaction between FcgammaRII and
      these kinases are not elucidated. To asses this problem we isolated high
      molecular weight complexes of cross-linked FcgammaRII from non-ionic detergent
      lysates of U937 monocytic cells. CD55, a glycosylphosphatidylinositol-anchored
      protein, a ganglioside GM1 and Lyn, a Src family tyrosine kinase, were also
      located in these complexes. Gradient centrifugation demonstrated that the
      complexes containing cross-linked FcgammaRII displayed a low buoyant density. The
      FcgammaRII present in the complexes underwent tyrosine phosphorylation. Cross
      linked FcgammaRII and Lyn occupied common 100-200 nm detergent-resistant membrane
      fragments, as demonstrated by immunoprecipitation and microscopy studies.
      Pretreatment of the cells with beta-cyclodextrin, a cholesterol acceptor,
      depleted membrane cholesterol and released CD55, GM1 and Lyn from the detergent
      resistant complexes. In parallel, the association of Lyn with cross-linked
      FcgammaRII was disrupted and phosphorylation of the receptor inhibited.
      Reincorporation of cholesterol evoked the relocation of Lyn into the detergent
      resistant membrane fraction and restored both Lyn association with cross-linked
      FcgammaRII and tyrosine phosphorylation of the receptor. Our data demonstrate
      that cholesterol-enriched membrane rafts can facilitate tyrosine phosphorylation
      of clustered FcgammaRII by Lyn kinase.

PMID- 11298325
TI  - Interleukin-18 enhances the production of interleukin-8 by eosinophils.
AB  - Interleukin-18 (IL-18), a proinflammatory cytokine, leads to IFN-gamma production
      by NK or T cells, induces Th1 differentiation and suppresses IgE synthesis by B
      cells when acting on responding cells together with IL-12. IL-18 also exhibits
      biological activities related to allergic inflammation such as histamine or IL-4
      release from basophils and accumulation of eosinophils in localized lesions in
      allergic model mice. In this study, Reverse transcription (RT)-PCR analysis
      revealed that IL-18 receptor alpha chain mRNA was expressed in both freshly
      prepared eosinophils and two eosinophilic cell lines (YY-1 and EoL-1 cells). Flow
      cytometry and RT-PCR analyses revealed that the treatment of YY-1 cells with n
      butyric acid promoted cell maturation and caused an enhancement of IL-18 receptor
      alpha chain expression. IL-18 had little effect on the survival of peripheral
      eosinophils, but it dose-dependently augmented IL-8 synthesis by YY-1 cells. In
      addition, IL-18-mediated up-regulation of IL-8 expression in eosinophils from a
      patient suffering from hyper-eosinophilic syndrome was confirmed. Our findings
      using peripheral blood eosinophils and eosinophilic cell line suggest the
      functional importance of IL-18 in the induction of IL-8 and a potential
      proinflammatory role in allergy.

PMID- 11298324
TI  - Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and
      dependence of CD163 signaling on CKII and protein kinase C.
AB  - CD163 is a recently identified member of the scavenger receptor cysteine-rich
      superfamily, which is expressed on peripheral blood monocytes and most tissue
      macrophages and is thought to play an important role in the regulation of the
      inflammatory response of these cells. Cross-linking of CD163 on glucocorticoid
      stimulated macrophages results in the secretion of several proinflammatory
      cytokines, but the precise mechanism of CD163 mediated signal transduction is not
      understood. The existence of several CD163 isoforms, which differ in the
      structure of their cytoplasmic domains and putative phosphorylation sites,
      suggests that these isoforms also differ in their signaling mechanism. Using the
      Yeast Two-Hybrid system and further in vitro and in vivo studies, we identified
      the regulatory beta-subunit of casein kinase II (CKII), which specifically binds
      to the cytoplasmic domain of CD163 and its isoforms. We also found, that in vitro
      the CD163 isoforms differ in their association with the CKII holoenzyme and in
      the phosphorylation by CKII. Furthermore, we demonstrated that the cytoplasmic
      domains of CD163 variants are phosphorylated by PKC-alpha in vitro. Inhibition
      studies using specific kinase inhibitors reveal that both CKII and PKC are
      involved in the CD163 signaling mechanism resulting in the secretion of
      proinflammatory cytokines.

PMID- 11298326
TI  - Evolutionary dynamics of the human immunoglobulin kappa locus and the germline
      repertoire of the Vkappa genes.
AB  - We have determined the entire nucleotide sequence of the human immunoglobulin
      kappa locus, comprising a total of 1,010,706 nucleotides. The 76 Vkappa genes
      found by a hybridization-based approach and their classification in 7 families
      were confirmed. A Vkappa orphon located near the locus was also sequenced. In
      addition, we identified 55 novel Vkappa relics and truncated pseudogenes, which
      establish 5 new families. Among these 132 Vkappa genes, 46 have open reading
      frames. According to the databases and the literature, 32 unique Vkappa genes and
      5 identical gene pairs form VJ-joints, 27 unique genes and 4 gene pairs are
      transcribed, and 25 unique genes and 4 gene pairs produce functional proteins.
      The Vkappa gene locus contains a 360-kb inverted duplication, which harbors 118
      Vkappa genes. A comparison of the duplicated Vkappa genes suggests positive
      selection on the complementarity-determining regions of the duplicated genes by
      point mutations. The entire duplication unit was divided into 13 blocks, each of
      which has its distinct nucleotide sequence identity to its duplication
      counterpart (98.1 - 99.9 %). An inversion-mediated mechanism is suggested to
      generate the high-homology blocks. Based on the homology blocks and the mutation
      rates, the inverted duplication is assumed to have taken place approximately 5
      million years ago. An orphon Vkappa gene near the kappa locus and a cluster of
      five Vkappa orphons on chromosome 22 have no counterparts within the kappa locus.
      This suggests possible mechanisms of the transposition of orphon Vkappa genes.

PMID- 11298327
TI  - Conformational alterations during biosynthesis of HLA-DR3 molecules controlled by
      invariant chain and HLA-DM.
AB  - HLA-DM is known to catalyze the exchange of class II-associated invariant chain
      (Ii) peptide (CLIP) for cognate peptide during biosynthesis. In DM-negative cells
      HLA-DR3 molecules have been shown to predominantly present CLIP and to lack the
      DR3-specific mAb epitope 16.23, which has led to the assumption that CLIP
      prevents binding of mAb 16.23. In the present study we show that CLIP does not
      prohibit 16.23 epitope expression, but that the formation of this epitope is
      directly influenced by interactions of the DR molecule with Ii and DM. Detergent
      solubilized DR3 from wild-type as well as DM(-) cells bound CLIP in a 16.23(+)
      mode. On cells, however, neither CLIP nor antigenic peptide bound to DR3 in a
      16.23(+) conformation, unless HLA-DM was expressed. Thus, HLA-DM appears to alter
      the conformation of DR3 in a peptide-independent fashion. Since in DM-deficient
      cells that also lack Ii, DR3 molecules assembled in a 16.23(+) conformation, we
      conclude that during biosynthesis Ii and DM exert opposing conformational
      constraints, characterized by suppressing or releasing 16.23 epitope expression.
      These results imply that DR3/peptide complexes, including DR3/ CLIP, can exist in
      two conformations depending on previous interaction with DM, but independent of
      the nature of the peptide bound. We show that these naturally occurring class II
      conformers can be selectively recognized by T cells.

PMID- 11298328
TI  - Clonal Th2 cells associated with chronic hypereosinophilia: TARC-induced CCR4
      down-regulation in vivo.
AB  - We analyzed the expression of chemokine receptors on clonal Th2-type CD4(+)CD3(-
      )lymphocytes isolated from blood of two patients with chronic hypereosinophilia.
      First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but
      neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4
      appeared following culture in human serum-free medium, suggesting that it was
      down-regulated in vivo. Indeed, patient's serum, but not control human serum,
      strongly down-regulated CCR4 expression on cultured Th2 cells. As high levels of
      TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic
      patients with CD3(-)CD4(+) clonal Th2 cells, we evaluated the effect of TARC
      neutralization in this system. Addition of a neutralizing anti-TARC mAb inhibited
      CCR4 down-regulation by patient's serum, indicating that circulating TARC
      contributed to CCR4 down-regulation on Th2 cells in vivo. Clonal Th2 cells did
      not secrete high levels of TARC themselves but induced a sustained production of
      TARC by monocyte-derived dendritic cells, a phenomenon that was inhibited by
      addition of blocking mAb against IL-4 receptor. We conclude that high circulating
      levels of TARC in serum of patients with chronic hypereosinophilia, most likely
      derived from antigen-presenting cells stimulated by Th2-type cytokines, induce
      down-regulation of CCR4 on Th2 cells in vivo.

PMID- 11298329
TI  - Phosphorylation of C3 by a casein kinase released from activated human platelets
      increases opsonization of immune complexes and binding to complement receptor
      type 1.
AB  - We have previously demonstrated that complement component C3 is phosphorylated
      both in vitro and in vivo by a casein kinase released from activated human
      platelets. In vitro, the studies have shown that cleavage of C3b by factor I is
      decreased, and binding to various target surfaces is enhanced by affecting the
      thiol ester. In the present study we have examined the effect of phosphorylation
      on the binding of C3b to complement receptor 1 (CR1, CD35). Upon phosphorylation
      by platelet casein kinase, C3b covalently bound to activated thiol Sepharose
      bound higher amounts of soluble recombinant CR1. Similar effects were
      demonstrated with two ELISA systems in which microtiter plates were coated with
      phosphorylated or unphosphorylated purified C3b or with C3 activated by the
      alternative pathway convertase. Phosphorylated C3b was also four times more
      efficient than unphosphorylated C3b in inhibiting the binding of complement
      opsonized human aggregated gammaglobulin to erythrocytes. A similar increase in
      binding was found at low serum concentrations when the C3 activation occurred in
      C3-deficient serum reconstituted with phosphorylated or unphosphorylated C3. In
      this serum system, using a monoclonal antibody specific for iC3b, we also
      demonstrated that the phosphorylated C3b was protected against cleavage to iC3b.
      Corresponding experiments using factor H showed a decrease in binding of both
      fluid-phase and bound C3b to factor H. We postulate that phosphorylation of C3 by
      activated platelets amplifies the complement-mediated binding of immune complexes
      to CR1 by three different mechanisms: decreased cleavage of C3b to iC3b,
      increased deposition of C3b to immune complexes, and increased binding of C3b to
      CR1.

PMID- 11298331
TI  - Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL
      37 on histamine release and prostaglandin D(2) production from mast cells.
AB  - Antimicrobial peptides, human beta-defensins (hBD-1/-2), and LL-37 (a peptide of
      human cathelicidin CAP18) are predominately expressed at epithelial tissues,
      where they participate in the innate host defense by killing invading
      microorganisms. In this study, to investigate the interactions between epithelial
      cell-derived antimicrobial peptides and mast cells, we evaluated the effects of
      hBD-1/-2 and LL-37 on mast cell functions using rat peritoneal mast cells. hBD-2
      and LL-37 but not hBD-1 induced histamine release and intracellular Ca(2+)
      mobilization, and hBD-2 was more potent than LL-37. Interestingly, histamine
      release and intracellular Ca(2+) mobilization elicited by hBD-2 and LL-37 were
      markedly suppressed by BAPTA-AM (an intracellular Ca(2+) chelating agent),
      pertussis toxin and U-73122 (a phospholipase C inhibitor). In addition, among the
      peptides examined, only hBD-2 significantly induced PGD(2) production, which was
      abolished by indomethacin (cyclooxygenase-1/-2 inhibitor) but not NS-398
      (cyclooxygenase-2 inhibitor), suggesting that hBD-2-induced PGD(2) production is
      mediated by cyclooxygenase-1. Likewise, the PGD(2) production was suppressed by
      pertussis toxin and U-73122. These observations suggest that hBD-2 and LL-37
      stimulate mast cells to mobilize intracellular Ca(2+) and release histamine or
      generate PGD(2) in a G protein-phospholipase C-dependent manner. Thus, hBD-2 and
      LL-37 may have modulatory effects on inflammatory reactions.

PMID- 11298330
TI  - IL-12-induced reversal of human Th2 cells is accompanied by full restoration of
      IL-12 responsiveness and loss of GATA-3 expression.
AB  - IL-12 is a potent inducer of IFN-gamma production and drives the development of
      Th1 cells. Human polarized Th2 cells do not express the signaling beta2-subunit
      of the IL-12R and, therefore, do not signal in response to IL-12. The question
      was raised as to what extent the loss of the IL-12Rbeta2 chain in Th2 cells has
      bearing on the stability of the human Th2 phenotype. In the present report, we
      show that restimulation of human fully polarized Th2 cells in the presence of IL
      12 primes for a shift towards Th0/Th1 phenotypes, accompanied by suppression of
      GATA-3 expression and induction of T-bet expression. These reversed cells are
      further characterized by a marked IL-12Rbeta2 chain expression and fully restored
      IL-12-inducible STAT4 activation. The IL-12-induced phenotypic shift proved to be
      stable as a subsequent restimulation in the presence of IL-4 and in the absence
      of IL-12 could not undo the accomplished changes. Identical results were obtained
      with cells from atopic patients, both with polyclonal Th2 cell lines and allergen
      specific Th2 cell clones. These findings suggest the possibility of restoring IL
      12 responsiveness in established Th2 cells of atopic patients by stimulation in
      the presence of IL-12, and that IL-12-promoting immunotherapy can be beneficial
      for Th2-mediated immune disorders, targeting both naive and memory effector T
      cells.

PMID- 11298332
TI  - Role of NKG2D in tumor cell lysis mediated by human NK cells: cooperation with
      natural cytotoxicity receptors and capability of recognizing tumors of
      nonepithelial origin.
AB  - NKG2D is a recently described activating receptor expressed by both NK cells and
      CTL. In this study we investigated the role of NKG2D in the natural cytolysis
      mediated by NK cell clones. The role of NKG2D varied depending on the type of
      target cells analyzed. Lysis of various tumors appeared to be exclusively natural
      cytotoxicity receptors (NCR) dependent. In contrast, killing of another group of
      target cells, including not only the epithelial cell lines HELA and IGROV-1, but
      also the FO-1 melanoma, the JA3 leukemia, the Daudi Burkitt lymphoma and even
      normal PHA-induced lymphoblasts, involved both NCR and NKG2D. Notably, NK cell
      clones expressing low surface densities of NCR (NCR(dull)) could lyse these
      tumors in an exclusively NKG2D-dependent fashion. Remarkably, not all of these
      targets expressed MICA/B, thus implying the existence of additional ligands
      recognized by NKG2D, possibly represented by GPI-linked molecules. Finally, we
      show that the engagement of different HLA class I-specific inhibitory receptors
      by either specific antibodies or the appropriate HLA class I ligand led to
      inhibition of NKG2D-mediated NK cell triggering.

PMID- 11298333
TI  - Neutralizing monoclonal antibodies can potentiate IL-5 signaling.
AB  - IL-5 is a major determinant in the survival, differentiation and effector
      functions of eosinophils. It mediates its effect upon binding and activation of a
      membrane bound receptor (R), composed of a ligand-specific alpha-chain and a beta
      chain, shared with the receptors for IL-3 and granulocyte-macrophage colony
      stimulating factor. We have generated and mapped the epitopes of three monoclonal
      antibodies (mAb) directed against this cytokine: the strong neutralizing mAb 5A5
      and 1E1, and the very weak neutralizing mAb H30. We found that H30 as well as 5A5
      can increase proliferation above the level induced by human (h)IL-5 alone, in a
      JAK-2-dependent manner, and at every sub-optimal hIL-5 concentration analyzed.
      This effect is dependent on mAb-mediated cross-linking of IL-5R complexes, and is
      only observed on cell lines expressing a hybrid human/mouse IL-5Ralpha-chain. We
      discuss these findings in view of the stoichiometric and topological requirements
      for an activated IL-5R. Since humanized anti-IL-5 mAb are currently in clinical
      testing, our findings imply that such mAb should be carefully evaluated for their
      potentiating effects.

PMID- 11298334
TI  - The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR
      gamma agonists induce apoptosis.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma is a nuclear hormone
      receptor that serves as a trans factor to regulate lipid metabolism. Intense
      interest is focused on PPAR-gamma and its ligands owing to its putative role in
      adipocyte differentiation. Little is known, however, about the functions of PPAR
      gamma in the immune system, especially in T lymphocytes. We demonstrate that both
      naive and activated ovalbumin-specific T cells from DO11.10-transgenic mice
      express PPAR-gamma mRNA and protein. In order to determine the function of PPAR
      gamma, T cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin
      or antigen and antigen-presenting cells. Simultaneous exposure to PPAR-gamma
      ligands (e. g. 15-deoxy-Delta(12, 14)-prostaglandin J(2), troglitazone) showed
      drastic inhibition of proliferation and significant decreases in cell viability.
      The decrease in cell viability was due to apoptosis of the T lymphocytes, and
      occurred only when cells were treated with PPAR-gamma, and not PPAR-alpha
      agonists, revealing specificity of this response for PPAR-gamma. These
      observations suggest that PPAR-gamma agonists play an important role in
      regulating T cell-mediated immune responses by inducing apoptosis. T cell death
      via PPAR-gamma ligation may act as a potent anti-inflammatory signal in the
      immune system, and ligands could possibly be used to control disorders in which
      excessive inflammation occurs.

PMID- 11298335
TI  - Characterization of murine polyreactive antigen-binding B cells: presentation of
      antigens to T cells.
AB  - Monoclonal polyreactive antibodies (Ab) can bind, at low affinity, a variety of
      different self and non-self antigens (Ag). Recent studies in humans showed that
      polyreactive Ab are expressed on the surface of a subset of peripheral B
      lymphocytes and clonal analysis revealed that a variety of different Ag can bind
      to single cells expressing these Ab. To see if these polyreactive Ag-binding B
      (PAB) cells also are present in mice, fluorescein-conjugated Ag and FACS sorting
      were used to identify and separate PAB cells from non-polyreactive Ag-binding B
      cells. Depending on the Ag used for screening, up to one-third of mouse splenic B
      cells displayed polyreactive Ag-binding properties. Confirmation that the Ag
      actually bound to surface Ig came from treating PAB cells with anti-Ig which
      inhibited Ag binding by up to 80 %. Further studies showed that PAB cells could
      present Ag to Ag-specific T cells, but despite their Ag-presenting ability, PAB
      cells from normal mice failed to trigger Ag-specific T cells to proliferate.
      Analysis of the co-stimulatory molecules B7-1 and B7-2 showed that these
      molecules were not expressed on PAB cells from normal mice. These findings argue
      that the lack of co-stimulatory molecules on PAB cells is the most likely
      explanation for their failure to stimulate Ag-specific T cells. The ability of
      PAB cells from normal mice to bind and present Ag to Ag-specific T cells, without
      causing them to proliferate, suggests that PAB cells may contribute to the
      induction and / or maintenance of immunological tolerance.

PMID- 11298336
TI  - Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific
      CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus
      load.
AB  - Therapeutic intervention with antiretroviral therapy (ART) enables the modulation
      of HIV virus load and hence provides a unique opportunity to study the
      consequences of varying antigen load on the phenotype of virus-specific CD8(+) T
      lymphocytes in a persistent human viral infection. The recent advent of
      tetrameric peptide / HLA class I complexes has enabled the direct phenotypic
      characterization of antigen-specific T cell populations ex vivo. Here, we use
      this technology to examine directly ex vivo the consequences of therapeutic
      manipulation of HIV virus load on the phenotype of HIV-specific CTL. Our
      observations show that: (1) distinct sequential activation patterns of CD8(+) T
      cells are associated with increasing virus load; (2) T cell receptor (TCR) down
      regulation without apoptosis represents an early event during the generation of a
      T cell response in a natural infection and precedes the emergence of two distinct
      antigen-specific CD8(+) T cell populations which differ in TCR and CD8 expression
      levels. Clear differences in surface Annexin V staining were observed between
      these populations. The observation that CTL activation, demonstrated by TCR and
      CD8 down-regulation, in response to rising levels of virus load, co-segregates
      with apoptosis only during later stages of the response indicates that antigen
      associated cell death is restricted to distinct subpopulations of CTL.

PMID- 11298337
TI  - Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and
      apoptosis-prone population.
AB  - Anergic/suppressive CD4(+)CD25(+) T cells exist in animal models but their
      presence has not yet been demonstrated in humans. We have identified and
      characterized a human CD4(+)CD25(+) T cell subset, which constitutes 7-10 % of
      CD4(+) T cells in peripheral blood and tonsil. These cells are a
      CD45RO(+)CD45RB(low) highly differentiated primed T cell population that is
      anergic to stimulation. Depletion of this small subset from CD4(+) T cells
      significantly enhances proliferation by threefold in the remaining CD4(+)CD25(-)
      T cells, while the addition of isolated CD4(+)CD25(+) T cells to CD4(+)CD25(-) T
      cells significantly inhibits proliferative activity. Blocking experiments suggest
      that suppression is not mediated via IL-4, IL-10 or TGF-beta and is cell-contact
      dependent. Isolated CD4(+)CD25(+) T cells are susceptible to apoptosis that is
      associated with low Bcl-2 expression, but this death can be prevented by IL-2 or
      fibroblast-secreted IFN-beta. However, the anergic/suppressive state of these
      cells is maintained after cytokine rescue. These human regulatory cells are
      therefore a naturally occurring, highly suppressive, apoptosis-prone population
      which are at a late stage of differentiation. Further studies into their role in
      normal and pathological situations in humans are clearly essential.

PMID- 11298338
TI  - Essential role of TGF-beta in the natural resistance to experimental allergic
      encephalomyelitis in rats.
AB  - Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune
      disease induced in susceptible rat strains by a single immunization with myelin
      basic protein (MBP). The Lewis (LEW) strain is susceptible to disease induction
      while the Brown Norway (BN) strain is resistant. This resistance involves non-MHC
      genes since congenic BN-1L rats, with LEW MHC on a BN-derived background, are
      also resistant. In the present study we show that, upon immunization with MBP,
      the non-MHC-encoded resistance to develop clinical EAE in BN-1L rats is
      associated with a decreased production of IFN-gamma. This may be due to a
      difference between LEW and BN-1L rats in their ability to produce regulatory
      cytokines such as IL-4, IL-10 and TGF-beta. In comparison to LEW rats, immune
      lymph node cells from BN-1L rats express an increased amount of IL-4 mRNA but
      produce less IL-10. Furthermore, the sera from BN-1L rats contain higher amounts
      of active TGF-beta1. Therefore, we have investigated the involvement of IL-4 and
      TGF-beta in the resistance of BN-1L rats to develop EAE using neutralizing mAb.
      Neutralization of TGF-beta, but not IL-4, renders BN-1L rats susceptible to
      clinical EAE without affecting the proliferation or the cytokine repertoire of
      immune lymph node cells. With respect to the origin of the endogenous TGF-beta
      production, we excluded the involvement of CD8 T cells and discuss a possible
      role of platelets and of CD4 T cells exhibiting the CD45RC(low) phenotype.

PMID- 11298339
TI  - TARPP, a novel protein that accompanies TCR gene rearrangement and thymocyte
      education.
AB  - Studies on thymic T cell development have usually concentrated on cell surface
      molecules. However, intracellular proteins expressed only in thymocytes have
      never been described. Here we report the discovery of a novel thymocyte-specific
      protein, named TARPP, which represents a high molecular mass ( approximately 100
      kDa) variant of the previously identified protein ARPP-21 ( approximately 21
      kDa). TARPP is a cytosolic protein that is expressed at high levels in immature
      thymocytes. It appears concomitant with the commitment to T cell lineage, and its
      expression is switched off as a consequence of TCR engagement during positive
      selection. Such an expression pattern, correlating with the rearrangement of the
      TCR genes and thymocyte education, suggests a role for TARPP during this
      important phase of thymocyte development.

PMID- 11298340
TI  - B cells activated via CD40 and IL-4 undergo a division burst but require
      continued stimulation to maintain division, survival and differentiation.
AB  - T cell stimulation of B cell proliferation during T-B collaboration requires
      membrane-bound stimulatory ligands, such as CD40 ligand and the secretion of
      soluble cytokines, such as IL-4. Nevertheless, it remains unclear whether T cell
      contact is required to provoke each consecutive B cell division, or whether B
      cells divide in a T cell-free burst following the initial stimulation. To test
      this, naive B cells were cultured with anti-CD40 monoclonal antibody (mAb) and IL
      4 and, after various times, these stimuli were removed and the cells re-cultured
      with or without further stimulation. Following stimulus removal, B cells were
      able to continue proliferating, with the size of the B cell burst dependent on
      the strength of the initial anti-CD40 mAb stimulus. Furthermore, in the absence
      of activating signals from anti-CD40 and/or IL-4, re-cultured B cells died
      rapidly. In addition, B cells undergoing a stimulus-free division burst could
      switch to IgG1. Thus, maximal B cell proliferation, differentiation and survival
      may require continued, although not necessarily consecutive, cognate interactions
      with T cells. These results suggest that antigen persistence and T cell help are
      necessary to sustain B cell proliferation and differentiation in vivo.

PMID- 11298341
TI  - The role of homotypic interactions in the differentiation of B cell precursors.
AB  - Numerous studies have demonstrated that B lymphopoiesis is dependent upon a
      stromal cell microenvironment. Many of the stromal cell-derived factors and cell
      surface interactions that regulate B cell development have been identified;
      however, little consideration has been paid to the intimate interactions known to
      occur among B cell precursors themselves in both the fetal liver and marrow
      microenvironments. In this study we show that homotypic interactions between B
      cell precursors play an important role in promoting the development of mature B
      cells. We used an in vitro assay system to demonstrate that the function of
      stromal cells can be replaced by culturing B cell precursors in proximity. B cell
      precursors isolated from bcl-2 transgenic mice were used to rule out the
      possibility that improved survival, hypothesized to result from culturing
      precursors in proximity, solely accounted for the observed increase in B cell
      maturation. The putative maturation signal(s) were shown to be dependent upon
      direct contact between precursors rather than the release of soluble factors from
      nearby cells. Upon examination of the potential role of several known cell
      surface proteins, we found that blocking mu heavy chains with monovalent Fab
      antibody fragments dramatically inhibited maturation, in a stage-specific manner.
      Together these results suggest that a major function of stromal cells in vivo may
      be to act as a docking site to promote critical preB-preB homotypic interactions
      and ensuing signals. Further, the antibody blocking experiments raise the
      interesting possibility that interactions between B cell precursors themselves
      may promote and/or regulate preB cell receptor-driven signals.

PMID- 11298342
TI  - The complement receptor 3, CR3 (CD11b/CD18), on T lymphocytes: activation
      dependent up-regulation and regulatory function.
AB  - The complement receptor 3 (CR3; CD11b/CD18) is present exclusively on leukocytes,
      particularly on NK cells, monocytes and polymorphonuclear neutrophils.
      Approximately 10% of peripheral T lymphocytes and, as we found now mainly CD8(+)
      cells, expressed CD11b. Upon stimulation, however, expression of CD11b was up
      regulated also on CD4(+) cells. Stimulation of T cells either by cross-linked
      anti-CD3 and IL-2 or by mononuclear cells and mitogen yielded up to 28% CD11b(+)
      T cells. The majority of CD11b(+) T cells also expressed CD56. T cell lines
      established from healthy donors were also found to express CR3. When restimulated
      up to 90% of cells became positive for CD11b making those cells an ideal tool for
      studying the functional role of CD11b. Antibodies to CD11b and bona fide ligands
      for the complement receptor inhibited the anti-CD3-induced T cell proliferation
      and as well as IL-2 release. In contrast, proliferation of a CD11b(-) T cell line
      was not inhibited. Taken together, our data indicate an activation-dependent
      expression of the complement receptor on T cells and suggest a regulatory
      function.

PMID- 11298343
TI  - Exogenous peptides enter the endoplasmic reticulum of TAP-deficient cells and
      induce the maturation of nascent MHC class I molecules.
AB  - MHC class I molecules assemble within the endoplasmic reticulum (ER) in complexes
      that include beta2-microglobulin (beta(2)m), the transporter associated with
      antigen processing (TAP)and several additional chaperones. Release of class I
      complexes from the ER is thought to require the binding of an appropriate
      endogenous peptide, predominantly delivered from the cytosol to the ER by TAP. It
      was recently demonstrated that exogenous synthetic peptide could 'directly' enter
      the ER of intact cells, independently of TAP function, and bind to the class I
      molecule H-2K(b).In TAP-deficient cells, we show that nascent K(b) or K(b)-L(d)
      chimeric molecules have a high trafficking background; 50-80% of these class I
      molecules are released from the ER independently of TAP function or the addition
      of exogenous peptide. The addition of exogenous K(b) cognate peptides enhanced
      the release of these class I molecules only slightly over the high background.
      The chimeric class I-b molecule, M3-L(d), differs from K(b)-L(d) only in its
      peptide binding domains, and M3-L(d) preferentially binds N-formylated peptides,
      which are rare in eukaryotic cells. Release of M3-L(d) from the ER in the absence
      of exogenous peptide was negligible. Addition of exogenous formylated peptides
      induced significant trafficking and surface expression of M3-L(d). These
      observations suggest that peptide binding is necessary for class I release from
      the ER even in TAP-deficient cells. These results demonstrate that exogenous
      peptide not only enters the ER of intact cells independently of TAP but also
      functionally induces class I antigen presentation.

PMID- 11298344
TI  - Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases.
AB  - The human CD5 lymphocyte cell surface co-receptor modulates activation and
      differentiation responses mediated by the antigen-specific receptor of T and B
      cells. CD5 is phosphorylated following lymphocyte activation; however, the exact
      sites and kinases involved are yet to be determined. Jurkat T cell transfectants
      expressing tyrosine-mutated CD5 molecules have been used to show that residues
      Y429 and Y463 are targeted in vivo by protein tyrosine kinases following cell
      stimulation with anti-CD3 mAb or pervanadate. This is in agreement with data from
      direct in vitro kinase assays using purified recombinant Lck and Fyn protein
      tyrosine kinases. The analysis of Lck- and CD3-deficient Jurkat cells shows that
      tyrosine phosphorylation of CD5 requires Lck activity. We propose that T cell
      activation mediates CD5 tyrosine phosphorylation at residues Y429 and Y463 mainly
      through the activation of Lck.

PMID- 11298345
TI  - CD95 is required for the early control of parasite burden in the liver of
      Leishmania donovani-infected mice.
AB  - In this study we show an increased incidence of T cell apoptosis in the liver and
      spleen of mice infected with Leishmania donovani. T cells from L. donovani
      infected mice were found to be increasingly susceptible to CD95-mediated
      apoptosis in vitro, compared to controls. To test if suboptimal T cell function
      resulting from CD95-mediated apoptosis contributes to sustained parasite burden
      in L. donovani parasitized mice, B6.gld mice (lacking functional CD95 ligand)
      were infected with L. donovani. Surprisingly, at four different time points no
      difference in levels of T cell apoptosis in the spleen and liver was found
      between these mice and controls following intravenous delivery of L. donovani
      amastigotes, indicating that the CD95 / CD95L interaction is not essential for T
      cell apoptosis in the L. donovani-infected liver and spleen. However, B6.gld mice
      were increasingly susceptible to L. donovani infection, associated with less
      efficient granuloma formation in the liver and uncontrolled parasite growth in
      the spleen. Late in infection (day 56 post-infection), B6.gld mice had higher
      numbers of IFN-gamma-producing CD4(+) T cells in the liver and spleen, indicating
      a role for CD95 signaling in the homeostasis of this subset of cytokine-producing
      T cells in L. donovani-parasitized mice. Adoptive transfer of CD4(+) and CD8(+) T
      cells into recombinase activating gene 1 knockout (RAG-1(- / -)) recipients,
      revealed that CD95L expressed on CD4(+) T cells contributes to early control of
      L. donovani infection in the liver via mechanisms that are independent of
      granuloma formation and induction of apoptosis. These results indicate important
      roles for CD95 and CD95L that are unrelated to regulation of apoptosis in the
      early control of L. donovani infection.

PMID- 11298346
TI  - Human T cell subset commitment determined by the intrinsic property of antigen:
      the proteolytic activity of the major mite allergen Der p 1 conditions T cells to
      produce more IL-4 and less IFN-gamma.
AB  - The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 elicits IgE
      antibody responses in a significant proportion of patients suffering from dust
      mite allergy. We have recently shown that Der p 1 proteolytically cleaves a cell
      surface molecule involved in the homeostatic control of human IgE synthesis,
      namely the IL-2 receptor (CD25) on T cells. As a result, these T cells show
      markedly diminished proliferation and IFN-gamma secretion in response to
      stimulation by anti-CD3 antibody. However, these observations still leave open
      the important issue of whether CD25 cleavage, and the consequent suppression of
      IFN-gamma secretion, leads to enhanced IL-4 secretion, and whether such cytokine
      changes would be exhibited by both CD4 and CD8 T cells. Here we demonstrate for
      the first time that the proteolytic activity of Der p 1 biases human CD4 and CD8
      T cells towards a type 2 cytokine profile. Our data provide compelling evidence
      for the role of the proteolytic activity of Der p 1 in creating a
      microenvironment conducive for IgE synthesis.

PMID- 11298347
TI  - The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded
      chemokine MC148, inhibits the CCR10 receptor.
AB  - The viral chemokine antagonist vMIP-II encoded by human herpesvirus 8 (HHV8) and
      MC148 encoded by the poxvirus - Molluscum contagiosum - were tested against the
      newly identified chemokine receptor CCR10. As the CCR10 ligand ESkine / CCL27 had
      the highest identity to MC148 and because both chemokines are expressed in the
      skin we suspected MC148 to block CCR10. However, in calcium mobilization assays
      we found MC148 unable to block CCR10 in micromolar concentrations in contrast to
      vMIP-II. (125)I-MC148 was only able to bind to CCR8, but not to CCR10, CCR11,
      CXCR6 / BONZO, APJ, DARC or the orphan receptors BOB, EBI-II, GPR4, GPR17, HCR or
      RDC1. We conclude that MC148 is a highly selective CCR8 antagonist conceivably
      optimized to interfere with NK cell and monocyte invasion, whereas the broad
      spectrum antagonist vMIP-II protects HHV8 by blocking multiple receptors.

PMID- 11298348
TI  - Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a
      case for tissue injury by molecular mimicry.
AB  - Anti-DNA autoantibodies are the hallmark of human and murine systemic lupus
      erythematosus (SLE), an autoimmune rheumatic disease of unknown etiology. Some of
      these antibodies are believed to be pathogenic for kidney tissue and to initiate
      immune glomerulonephritis. However, the mechanisms by which anti-DNA antibodies
      participate in tissue injury remain controversial. We have studied the in vivo
      pathogenicity of anti-DNA monoclonal antibodies in immune deficient mice, using a
      panel of murine B cell hybridomas. No consistent genetic or immunochemical
      differences were found between pathogenic and non-pathogenic anti-DNA antibodies.
      However, the two antibody populations differed in their cross-reaction with the
      acidic actin-binding protein, alpha-actinin, that is known to play a major role
      in the structural integrity of glomerular filtration components. These results
      suggest that kidney dysfunction in SLE may be facilitated by protein-nucleic acid
      antigenic mimicry.

PMID- 11298349
TI  - Activation of beta(1) integrins mediates proliferation and inhibits apoptosis of
      intestinal CD4-positive lymphocytes.
AB  - A characteristic of lamina propria lymphocytes (LPL) is their low proliferative
      response to stimuli of the CD3 pathway. beta(1) integrins were expressed on LPL;
      however, their function is unknown. Therefore, we determined whether beta(1)
      integrins contribute to T cell responses by providing costimulatory signals.
      Integrins on CD4(+) LPL of controls and patients with inflammatory bowel disease
      were characterized by flow cytometry. Cells were stimulated by anti-CD3 or anti
      CD2 antibodies either alone or in combination with a stimulatory beta(1) integrin
      antibody (12G10). Proliferation and apoptosis were measured by [(3)H]thymidine
      pulsing or flow cytometry. Cytokine mRNA and apoptosis-related transcripts were
      quantified by reverse transcriptase-PCR. We demonstrated that beta(1) integrin
      costimulation restored CD3-induced proliferation of CD4(+) LPL and reduced
      activation-induced apoptosis. Activation of beta(1) integrins by addition of
      12G10 antibody to CD3-stimulated cells restored their capacity to express
      proinflammatory cytokine transcripts. Further, expression of the activated form
      of beta(1) integrins was significantly elevated on LPL from inflamed mucosa.
      These studies demonstrate that beta(1) integrin costimulation modulates the
      response of LPL after TCR stimulation. An increased expression of activated
      beta(1) integrins on LPL in intestinal inflammation may abolish their
      unresponsiveness to antigens and perpetuate the inflammatory process.

PMID- 11298350
TI  - Tumor-associated antigens identified by mRNA expression profiling induce
      protective anti-tumor immunity.
AB  - Defined tumor-associated antigens (TAA) are attractive targets for anti-tumor
      immunotherapy. Here, we describe a novel genome-wide approach to identify
      multiple TAA from any given tumor. A panel of transplantable thymomas was
      established from an inbred p53-/- mouse strain. The resulting tumors were
      examined for gene expression by mRNA microarray scanning. This analysis revealed
      heterogeneity of the tumors in agreement with the assumption that they represent
      different tumorigenic events. Several genes were overexpressed in one or more of
      the tumors. To examine whether overexpressed genes might be used to identify TAA,
      mice were immunized with mixtures of peptides representing putative cytotoxic T
      cell epitopes derived from one of the gene products. Indeed, such immunized mice
      were partially protected against subsequent tumor challenge. Despite being
      immunized with bona fide self antigens, no clinical signs of autoimmune reactions
      were observed. Thus, it appears possible to evaluate the entire metabolism of any
      given tumor and use this information rationally to identify multiple epitopes of
      value in the generation of tumor-specific immunotherapy. We expect that human
      tumors express similar tumor-specific metabolic imprints, which may be used to
      identify patient-specific arrays of TAA. This may enable a multi-epitope based
      immunotherapy with improved prospects of clinical tumor rejection.

PMID- 11298351
TI  - Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive
      activity in vitro.
AB  - CD4(+)CD25(+) T cells in mice and rats are capable of transferring protection
      against organ-specific autoimmune disease and colitis and suppressing the
      proliferation of other T cells after polyclonal stimulation in vitro. Here we
      describe the existence in humans of CD4(+)CD25(+) T cells with the same in vitro
      characteristics. CD4(+)CD8(-)CD25(+) T cells are present in both the thymus and
      peripheral blood of humans ( approximately 10 % of CD4(+)CD8(-) T cells),
      proliferate poorly in response to mitogenic stimulation and suppress the
      proliferation of CD4(+)CD25(-) cells in co-culture. This suppression requires
      cell contact and can be overcome by the addition of exogenous IL-2. CD4(+)CD25(+)
      cells from thymus and blood were poor producers of IL-2 and IFN-gamma, and
      suppressed the levels of these cytokines produced by CD4(+)CD25(-) cells.
      However, CD4(+)CD25(+) PBL produced higher levels of IL-4 and similar amounts of
      IL-10 as CD4(+)CD25(-) cells. Regulatory CD4(+)CD25(+) T cells have an activated
      phenotype in the thymus with expression of CTLA-4 and CD122 (IL-2Rbeta). The fact
      that CD4(+)CD25(+) regulatory T cells are present with a similar frequency in the
      thymus of humans, rats and mice, suggests that the role of these cells in the
      maintenance of immunological tolerance is an evolutionarily conserved mechanism.

PMID- 11298352
TI  - Protection and injury: the differing roles of complement in the development of
      glomerular injury.
AB  - The role of complement in autoimmune glomerulonephritis (as in other autoimmune
      diseases) is paradoxical, in that complement activation mediates acute
      inflammatory injury, yet inherited deficiency of complement may predispose to
      immune complex disease in particular immune complex glomerulonephritis. We have
      investigated the role of complement in experimentally induced glomerulonephritis
      in C3-deficient mice, using antibodies against the mouse glomerular basement
      membrane (GBM). In the acute phase of the disease, which is initiated by binding
      of heterologous antibody to the GBM, we confirmed that the inflammatory injury
      was positively complement dependent, with C3-deficient mice developing less
      severe injury. In contrast, in the autologous phase of the disease, mediated by
      the immune response against the heterologous antibody fixed in the GBM, the
      disease was negatively complement dependent. That is, by 14 days after disease
      induction the C3-deficient mice had heavier proteinuria and more severe uremia (p
      < 0.001) compared to the complement sufficient mice. The C3-deficient mice also
      showed a greater accumulation of electron-dense deposits in the GBM. These
      findings were reproduced in an accelerated model of this disease in which C3
      deficient mice also develop more severe functional disturbance and demonstrate a
      higher rate of immune complex deposition. These data illustrate the potential for
      the net effect of complement to switch from a detrimental to a protective mode at
      different stages of autoimmune injury.

PMID- 11298353
TI  - Ontogeny, distribution and function of CD38-expressing B lymphocytes in mice.
AB  - Analysis of expression of CD38, CD45R (B220), IgM and IgD on splenic B
      lymphocytes from mice of different ages demonstrated CD38 on both immature
      (B220(+), BCR(-)) and mature (B220(+), BCR(+)) B lymphocytes. Similarly, CD38 is
      expressed as early as B220 on the surface of progenitor B cells in the bone
      marrow. In spite of expressing of CD38 and IgM, neonatal B cells, in contrast to
      the adult, failed to proliferate to either anti-CD38 or anti-IgM cross-linking
      when IL-4 was present. They did, however, respond to LPS and anti-CD40, and by 2
      weeks of age they began to respond to anti-CD38 and anti-IgM, reaching adult B
      cell levels by 4 weeks. Although the distribution of CD38 on adult B cells from
      most different lymphoid compartments was broadly similar, significantly higher
      levels of CD38 were expressed on peritoneal B lymphocytes. A detailed analysis,
      using IgM / IgD ratio and staining with anti-CD5 confirmed that B1 lymphocytes
      were expressing a high level of CD38. Interestingly, both immature B cells and
      peritoneal B1 lymphocytes were unresponsive to anti-CD38. However, they were
      activated by LPS or anti-CD40.

PMID- 11298355
TI  - Induction of oral tolerance to cellular immune responses in the absence of
      Peyer's patches.
AB  - Systemic hyporesponsiveness occurs following oral administration of antigen (oral
      tolerance) and involves the uptake and processing of antigen by the gut
      associated lymphoid tissue (GALT), which includes Peyer's patches (PP) lamina
      propria lymphocytes and mesenteric lymph nodes (MLN). Animals with targeted
      mutations of genes in the tumor necrosis factor (TNF) family have differential
      defects in the development of peripheral lymphoid organs including PP and MLN,
      and provide a unique opportunity to investigate the role of GALT structures in
      the induction of oral tolerance. Oral tolerance could not be induced in
      TNF/lymphotoxin (LT) alpha-/- mice, which are devoid of both PP and MLN, although
      these animals could be tolerized by intraperitoneal administration of antigen,
      demonstrating the requirement for GALT for oral tolerance induction. LTbeta-/-
      mice and LTalpha/LTbeta+/- animals do not have PP but could be orally tolerized,
      as measured by IFN-gamma production and delayed-type hypersensitivity responses
      by administration of both low or high doses of ovalbumin. To further investigate
      the requirement for PP, we tested the progeny of LTbeta-receptor-IgG-fusion
      protein (LTbetaRigG)-treated mice, which do not form PP but have an otherwise
      intact immune system. Although these animals had decreased fecal IgA production,
      they could be orally tolerized. Our results demonstrate that PP are not an
      absolute requirement for the induction of either high- or low-dose oral
      tolerance, although oral tolerance could not be induced in animals devoid of both
      PP and MLN.

PMID- 11298354
TI  - Immune protection against septic peritonitis in endotoxin-primed mice is related
      to reduced neutrophil apoptosis.
AB  - The innate immune system provides essential information about the presence of
      infectious danger and signals the activation and instruction of adaptive
      immunity. The present study addressed the question of whether prior exposure of
      the innate immune system to LPS may modulate host defense against acute septic
      peritonitis. We show that LPS priming 4 days, but not 2 days, prior to infection
      enhances bacterial clearance and improves survival of septic peritonitis. Immune
      protection in day 4 LPS-primed mice was specifically associated with a marked
      increase in the accumulation and activation of neutrophils at the site of
      infection. Accumulating neutrophils in day 4 LPS-primed mice exhibited a normal
      production of reactive oxygen metabolites in response to in vivo exposure to
      intestinal bacteria. The local increase in neutrophil numbers was found to result
      from a reduced rate of apoptotic cell death. Inhibition of neutrophil apoptosis
      in LPS-primed mice was mediated by soluble factor(s) distinct from G-CSF and GM
      CSF. Thus, engagement of pattern recognition systems prior to infection may
      improve host defense by amplifying the effector cell response of innate immunity.
      The results also provide in vivo evidence that apoptosis of inflammatory cells
      represents an important process for the control of host defense to infection.

PMID- 11298356
TI  - Functional plasticity of the LACK-reactive Vbeta4-Valpha8 CD4(+) T cells normally
      producing the early IL-4 instructing Th2 cell development and susceptibility to
      Leishmania major in BALB / c mice.
AB  - Early production of IL-4 by LACK-reactive Vbeta4-Valpha8 CD4(+) T cells instructs
      aberrant Th2 cell development and susceptibility to Leishmania major in BALB / c
      mice. This was demonstrated using Vbeta4(+)-deficient BALB / c mice as a result
      of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a
      Vbeta4-specific superantigen. The early IL-4 response was absent in these mice
      which develop a Th1 response to L. major. Here, we studied the functional
      plasticity of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells using BALB/ c mice
      inoculated with L. major shortly after infection with MMTV (SIM), i. e. before
      deletion of Vbeta4(+) cells. These mice fail to produce the early IL-4 response
      to L. major and instead exhibit an IFN-gamma response that occurs within LACK
      reactive Vbeta4-Valpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the
      production of IL-4 by these cells. These data suggest that the functional
      properties of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells are not irreversibly
      fixed.

PMID- 11298357
TI  - Injury-induced apoptosis of neurons in adult brain is mediated by p53-dependent
      and p53-independent pathways and requires Bax.
AB  - The mechanisms of injury-induced apoptosis of neurons within the CNS are not
      understood. We used a model of cortical injury in rat and mouse to induce
      retrograde neuronal apoptosis in thalamus. In this animal model, unilateral
      ablation of the occipital cortex causes unequivocal apoptosis of corticopetal
      projection neurons in the dorsal lateral geniculate nucleus (LGN) by 7 days
      postlesion. We tested the hypothesis that p53 and Bax regulate this retrograde
      neuronal apoptosis. We found, by using immunocytochemistry, that p53 accumulates
      in nuclei of neurons destined to undergo apoptosis. By immunoblotting, p53 levels
      increase ( approximately 150% of control) in nuclear-enriched fractions of the
      ipsilateral LGN by 5 days after occipital cortex ablation. p53 is functionally
      activated in nuclear fractions of the ipsilateral LGN at 5 days postlesion, as
      shown by DNA binding assay (approximately fourfold increase) and by
      immunodetection of phosphorylated p53. The levels of procaspase-3 increase at 4
      days postlesion, and caspase-3 is activated prominently at 5 days postlesion. To
      identify whether neuronal apoptosis in the adult brain is dependent on p53 and
      Bax, cortical ablations were done on p53 and bax null mice. Neuronal apoptosis in
      the dorsal LGN is significantly attenuated (approximately 34%) in p53(-/-) mice.
      In lesioned p53(+/+) mice, Bax immunostaining is enhanced in the ipsilateral
      dorsal LGN and Bax immunoreactivity accumulates at perinuclear locations in
      dorsal LGN neurons. The enhancement and redistribution of Bax immunostaining is
      attenuated in lesioned p53(-/-) mice. Neuronal apoptosis in the dorsal LGN is
      blocked completely in bax(-/-) mice. We conclude that neuronal apoptosis in the
      adult thalamus after cortical injury requires Bax and is modulated by p53.

PMID- 11298358
TI  - Topographic organization of suprachiasmatic nucleus projection neurons.
AB  - The mammalian circadian pacemaker, the hypothalamic suprachiasmatic nucleus
      (SCN), has two subdivisions. The core is located above the optic chiasm, receives
      primary and secondary visual afferents, and contains neurons producing vasoactive
      intestinal polypeptide and gastrin-releasing peptide. The shell largely surrounds
      the core, receives input from nonvisual sources and contains neurons producing
      arginine vasopressin and calretinin. In this study, we tested the hypothesis that
      SCN efferent projections are topographically organized with respect to the
      subdivision of origin. Injections of retrograde tracers were placed in major
      sites of efferent termination, described from prior studies that used anterograde
      tracers (Watts and Swanson, [1987] J. Comp. Neurol. 258:230-252; Watts et al.
      [1987] J. Comp. Neurol. 258:204-229). After retrograde tracer injections in the
      medial preoptic area, dorsomedial and paraventricular hypothalamic nuclei, bed
      nucleus of stria terminalis, paraventricular thalamic nucleus, zona incerta, and
      medial subparaventricular zone, retrogradely labeled SCN cells are clustered in
      the shell with few labeled neurons in the core. After injections centered in the
      lateral subparaventricular zone, peri-suprachiasmatic region, lateral septum, or
      ventral tuberal area, the majority of neuronal label is in the core with moderate
      to sparse neuronal label in the shell. Both subdivisions are labeled after
      injections in the paratenial thalamic nucleus. The same pattern of retrograde
      labeling is found with four tracers, cholera toxin-beta subunit, Fluoro-Gold, the
      Bartha strain of pseudorabies virus, and biotinylated dextran amine. These data
      extend our understanding of the significance of the division of the SCN into
      shell and core by demonstrating that the subdivisions differ in the pattern of
      projections. Together with prior observations that the subdivisions differ with
      respect to afferents, local connections, and neuroactive substances, the present
      study provides an anatomic basis for discrete control of circadian function by
      the SCN core and shell. In this novel view, the nature of the signal conveyed to
      areas receiving core or shell projections varies as a function of the subdivision
      from which innervation is derived.

PMID- 11298359
TI  - GABA and glycine-like immunoreactivity at axoaxonic synapses on 1a muscle
      afferent terminals in the spinal cord of the rat.
AB  - The object of this study was to analyze the synaptic interactions of identified
      muscle spindle afferent axon terminals in the spinal cord of the rat. Group 1a
      muscle afferents supplying the gastrocnemius muscle were impaled with
      microelectrodes in the dorsal white matter of the spinal cord and stained by
      intracellular injection with Neurobiotin. Postembedding immunogold techniques
      were used to reveal GABA- and glycine-like immunoreactivity in boutons
      presynaptic to afferent terminals in the ventral horn and the deep layers of the
      dorsal horn. Serial-section reconstruction was used to reveal the distribution of
      synaptic contacts of different types on the afferent terminals. The majority of
      afferent boutons received axoaxonic and made axodendritic or axosomatic synaptic
      contacts. In the ventral horn, 91% of boutons presynaptic to the afferent
      terminals were immunoreactive for GABA alone and 9% were immunoreactive for both
      GABA and glycine. The mean number of axo-axonic contacts received per terminal
      was 2.7, and the mean number of synaptic contacts at which the terminal was the
      presynaptic element was 1.4. In the deep layers of the dorsal horn, 58% of
      boutons presynaptic to afferent terminals were immunoreactive for GABA alone, 31%
      were immunoreactive for GABA and glycine, and 11% for glycine alone. The mean
      number of axoaxonic contacts received per afferent terminal in this region was
      1.6 and the mean number of synaptic contacts at which the terminal was the
      presynaptic element was 0.86. This clearly establishes the principle that
      activity in 1a afferents is modulated by several neurochemically distinct
      populations of presynaptic neuron.

PMID- 11298360
TI  - Lateral hypothalamus: early developmental expression and response to hypocretin
      (orexin).
AB  - Hypocretin is a recently discovered peptide that is synthesized by neurons in the
      lateral hypothalamic area (LH) and is believed to play a role in sleep
      regulation, arousal, endocrine control, and food intake. These functions are
      critical for the development of independent survival. We investigated the
      developmental profile of the hypocretin system in rats. Northern blot analysis
      showed that the expression of hypocretin mRNA increased from postnatal day 1 to
      adulthood. Both of the identified hypocretin receptor mRNAs were strongly
      expressed very early in hypothalamic development, and expression subsequently
      decreased in the mature brain. Immunocytochemistry revealed hypocretin-2 peptide
      expression in the cell bodies of LH neurons and in axons in the brain and spinal
      cord as early as embryonic day 19. Whole-cell patch clamp recordings from
      postnatal P1-P14 LH slices demonstrated a robust increase in synaptic activity in
      all LH neurons tested (n = 20) with a 383% increase in the frequency of
      spontaneous activity upon hypocretin-2 (1.5 microM) application. A similar
      increase in activity was found with hypocretin-1 application to LH slices.
      Hypocretin-2 evoked a robust increase in synaptic activity even on the earliest
      day tested, the day of birth. Furthermore, voltage-clamp recordings and calcium
      digital imaging experiments using cultured LH cells revealed that both hypocretin
      1 and -2 induced enhancement of neuronal activity occurred as early as synaptic
      activity was detected. Thus, as in the adult central nervous system, hypocretin
      exerts a profound excitatory influence on neuronal activity early in development,
      which might contribute to the development of arousal, sleep regulation, feeding,
      and endocrine control.

PMID- 11298361
TI  - Hypoglossal and reticular interneurons involved in oro-facial coordination in the
      rat.
AB  - Chewing, swallowing, breathing, and vocalization in mammals require precise
      coordination of tongue movements with concomitant activities of the mimetic
      muscles. The neuroanatomic basis for this oro-facial coordination is not yet
      fully understood. After the stereotaxic microinjection of retrograde and
      anterograde neuronal tracers (biotin-dextran, Fluoro-Ruby, Fluoro-Emerald, and
      Fluoro-Gold) into the facial and hypoglossal nuclei of the rat, we report here a
      direct bilateral projection of hypoglossal internuclear interneurons onto facial
      motoneurons. We also confirm the existence of a small pool of neurons in the
      dorsal part of the brainstem reticular formation that project ipsilaterally to
      both facial and hypoglossal nuclei. For precise tracer injections, both motor
      nuclei were located and identified by the electrical antidromic activation of
      their constituent motoneurons. Injections of retrograde tracers into the facial
      nucleus consistently labeled neurons in the hypoglossal nucleus. These neurons
      prevalently lay in the ipsilateral side, were small in size, and, like classic
      intrinsic hypoglossal local-circuit interneurons, had several thin dendrites.
      Reverse experiments - injections of anterograde tracers into the hypoglossal
      nucleus - labeled fine varicose nerve fiber terminals in the facial nucleus.
      These fiber terminals were concentrated in the intermediate subdivision of the
      facial nucleus, with a strong ipsilateral prevalence. Double injections of
      different tracers into the facial and the hypoglossal nuclei revealed a small,
      but constant, number of double-labeled neurons located predominantly ipsilateral
      in the caudal brainstem reticular formation. Hypoglossal internuclear
      interneurons projecting to the facial nucleus, as well as those neurons of the
      parvocellular reticular formation that project to both facial and hypoglossal
      nuclei, could be involved in oro-facial coordination.

PMID- 11298362
TI  - Demonstration of a rhodopsin-retinochrome system in the stalk eye of a marine
      gastropod, Onchidium, by immunohistochemistry.
AB  - The stalk eye of Onchidium sp. (Gastropoda, Mollusca) is the principal
      photoreceptor in a multiple photoreceptive system that consists of the stalk and
      dorsal eyes, dermal photoreceptor cells, and photosensitive neurons. To examine
      the localization of photopigments, the stalk eyes were immunostained with
      specific antibodies to rhodopsin, retinochrome, and retinal-binding protein
      (RALBP), which had been generated against squid retinal proteins. The retina of
      the stalk eye was divided into villous, pigmented, somatic, and neural layers. It
      was comprised mainly of two types of visual and pigmented supportive cells. The
      type 1 visual (VC1) cell was characterized by well-developed microvilli on its
      apical protrusion and photic vesicles in the cytoplasm. The photic vesicles were
      specifically blackened by prolonged osmification. The type 2 visual (VC2) cell
      had less numerous, shorter microvilli on its concave apical surface and lacked
      photic vesicles. The anti-squid rhodopsin antiserum was localized specifically to
      the villous layer that corresponded to the VC1 microvilli. With the anti
      retinochrome peptide antibody, the somatic layer showed specific but patchy,
      positive staining that corresponded to the cytoplasm of the VC1 cells. Because
      the photic vesicles are known to contain retinochrome, these results indicate
      that this retinochrome is localized in the VC1 cytoplasm. Anti-RALBP antibody
      stained the supranuclear cytoplasm to the distal cytoplasm of VC1 cells. This is
      the first demonstration of the localization of RALBP in the Gastropoda Onchidium
      stalk eye. In squid retina that were immunostained as positive controls, the anti
      rhodopsin antibody stained rhabdomeric microvilli, the anti-retinochrome antibody
      stained the inner segment and the basal region of the outer segment, and the anti
      RALBP antibody stained the outer and inner segments, respectively. These results
      suggest that the rhodopsin-retinochrome system that has been established in
      cephalopod eyes is present in the Onchidium stalk eye.

PMID- 11298363
TI  - Targeting of serotonin 1A receptors to dopaminergic neurons within the
      parabrachial subdivision of the ventral tegmental area in rat brain.
AB  - Serotonin (5-hydroxytryptamine [5-HT]) modulates dopamine-related cognitive
      functions and motor activity through activation of selective receptor subtypes
      including 5-HT1A. Potential targets for these 5-HT1A-mediated actions of 5-HT
      include mesocortical and mesolimbic dopaminergic neurons having partially
      segregated distribution in the parabrachial and paranigral subdivisions of the
      ventral tegmental area (VTA), respectively. We therefore examined the
      ultrastructural immunocytochemical localization of the 5-HT1A receptor in the
      parabrachial (VTApb) and paranigral (VTApn) subdivisions of rat VTA, to determine
      1) the functional sites for receptor activation, and 2) the cellular associations
      between this receptor and dopaminergic neurons identified by their tyrosine
      hydroxylase (TH) content. In each region, 5-HT1A immunoreactivity was mainly
      observed in somatodendritic profiles, but it was also present in small
      unmyelinated axons and in a few axon terminals and glia, suggesting a role for 5
      HT1A receptors in presynaptic and glial functions, as well as postsynaptic
      neuronal activation, in VTA. In somatodendritic profiles, 5-HT1A gold particles
      were mainly localized to tubulovesicles presumed to be smooth endoplasmic
      reticulum. In addition, however, in distal dendrites receiving multiple inputs
      the receptor was targeted to selective postsynaptic junctions, or more randomly
      distributed on nonsynaptic portions of the plasma membrane. Of the 5-HT1A-labeled
      dendrites, 64% in VTApb and 44% in VTApn contained TH. These findings suggest a
      reserve of cytoplasmic 5-HT1A receptors that are mobilized to functional
      postsynaptic sites on the plasma membrane by afferent input to distal dendrites
      in the VTA. They also indicate that 5-HT1A activation may affect a larger
      population of dopaminergic neurons in VTApb compared with VTApn, thus having a
      potentially greater impact on cognitive functions modulated by mesocortical
      dopaminergic neurons.

PMID- 11298364
TI  - Candidates for extraocular photoreceptors in the cockroach suggest homology to
      the lamina and lobula organs in beetles.
AB  - Using light- and electron microscopic methods, we describe two novel putative
      extraocular photoreceptor organs in the optic lobes of the cockroaches Leucophaea
      maderae and Blaberus craniifer. The lamina organ is an elongated structure distal
      to the first optic chiasm, adjacent to the anterior edge of the lamina. The
      lobula organ is situated on the anterior distal surface of the lobula. In cross
      sections through the pigment-free organs, cell bodies are arranged in a closed or
      open circle and are interconnected by desmosomes. They send protrusions with
      rhabdom-like microvilli into a common, central space apparently filled with
      extracellular matrix. A different cell type gives rise to electron-dense
      lamellae, which also extend into the central space and partly join to form a
      common lamellar bundle. Axonal processes extend from the microvillar cells and
      run along the outer surface of the organs to the neighboring optic neuropils. The
      organs receive multiple efferent innervation from neurosecretory axons. Both
      organs show strong immunostaining with an antiserum against Arabidopsis
      cryptochrome 2 that is associated with the lamellated structure in the central
      lumen. The specific features of the organs suggest that they are homologous to
      similar organs in the optic lobe of beetles and may serve a role as extraocular
      photoreceptors for light entrainment of the circadian system.

PMID- 11298365
TI  - Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of
      Niemann-Pick C disease.
AB  - The BALB/c mouse model of Niemann-Pick type C (NPC) disease exhibits
      neuropathological similarities to the human condition. There is an age-related
      cerebral atrophy, demyelination of the corpus callosum, and degeneration of
      cerebellar Purkinje cells in the NPC mouse. In human NPC, many cortical and
      subcortical neurons contain neurofibrillary tangles, which are thought by some
      investigators to play an important role in the neurodegenerative process. The
      purpose of the present study was to determine whether neurodegeneration occurs in
      the NPC mouse, in brain regions other than the cerebellum and whether the
      degeneration is related to the presence of neurofibrillary tangles. Using light
      microscopic methods with immunohistochemistry, electron microscopy, and cell
      counting methods, 11-week-old NPC(+/+) and NPC(-/-) animals were examined. In the
      NPC(-/-) mice, there were 96% fewer Purkinje cells, 28% fewer neurons in the
      prefrontal cortex, 20% fewer neurons in the thalamus, and 63% fewer glial cells
      in the corpus callosum. On the other hand, previous studies indicate normal
      numbers of neurons and glial cells in these same neuroanatomical regions in young
      NPC(-/-) mice. There were normal numbers of cholinergic neurons in sections
      assessed in the striatum and basal forebrain in the 11-week-old animals and no
      evidence of neurofibrillary tangles within cells. The present data indicate that
      both neurons and glial cells die in the NPC mouse but that all cells are not
      equally vulnerable. There was no evidence for neurofibrillary tangles in the NPC
      mouse, and therefore the degenerative process in the mouse is unrelated to the
      neurofibrillary tangle.

PMID- 11298366
TI  - Neuronal plasticity and formation of new synaptic contacts follow pyramidal
      lesions and neutralization of Nogo-A: a light and electron microscopic study in
      the pontine nuclei of adult rats.
AB  - Regeneration and compensatory sprouting are limited after lesions in the mature
      mammalian central nervous system in contrast to the developing central nervous
      system (CNS). After neutralization of the growth inhibitor Nogo-A, however,
      massive sprouting and rearrangements of fiber connections occurred after
      unilateral pyramidal tract lesions in adult rats: Corticofugal fibers from the
      lesioned side crossed the midline of the brainstem and innervated the
      contralateral basilar pontine nuclei. To determine whether these newly sprouted
      fibers formed synaptic contacts, we analyzed the corticofugal fibers in the
      basilar pontine nuclei contralateral to the lesion by light and electron
      microscopy 2 weeks after pyramidotomy and treatment with the Nogo-A-inhibiting
      monoclonal antibody IN-1 (mAb IN-1). The mAb IN-1, but not a control antibody,
      led to structural changes in the basilar pons ipsilateral and contralateral to
      the lesion site. Fibers sprouted across the pontine midline and terminated
      topographically. They established asymmetric synaptic contacts with the
      characteristics of normal corticopontine terminals. These results show that adult
      CNS fibers are able to sprout and to form new synaptic contacts after a lesion
      when a growth-permissive microenvironment is provided.

PMID- 11298367
TI  - Cardiac findings in an individual with neurofibromatosis 1 and sudden death.
AB  - Vascular lesions in neurofibromatosis 1 (NF1) are infrequently recognised as
      manifestations of the disease, yet they can produce serious complications. Most
      individuals with NF1 vasculopathy are asymptomatic, which may contribute to
      underestimation of its frequency. A recent study indicates that vascular changes
      in individuals with NF1 contribute to mortality at younger ages. We report the
      sudden death of a young man with NF1. On autopsy examination there was evidence
      of an intramyocardial vasculopathy characteristic of the vascular pathology
      previously described in NF1. Other cardiac findings included non-specific
      cardiomyopathic changes, myocardial fibrosis, and a "floppy" mitral valve.

PMID- 11298368
TI  - Atypical presentation of amniotic band sequence.
AB  - Amniotic Band Sequence (ABS) is a disruption sequence that results in a variable
      group of abnormalities secondary to the disruption process and subsequent
      deformations. The incidence of ABS ranges from 1:1,200 to 1:15,000 live-born, and
      is even higher in still-born [Froster and Baird, 1993: Am J Med Genet 46:497
      500]. The pathophysiology of ABS remains controversial, but a close look to
      critical periods of embryogenesis and/or organogenesis has helped in
      understanding pathogenetic mechanisms leading to the ABS disruption. The
      abnormalities are typically limited to external structures; however, associated
      internal malformations as seen in the case reported here may occur [Hunter and
      Carpenter, 1986: Am J Med Genet 24:691-700]. The prognosis depends on the
      severity of the abnormalities and the involvement of internal organs [Froster and
      Baird; 1993: Am J Med Genet 46:497-500; Levy, 1998: Ped Rev 19:249].

PMID- 11298370
TI  - Spontaneous fetal loss rates in a non-selected population.
AB  - The objective of this work was to determine the rate of spontaneous fetal loss up
      to 28 weeks of gestation in uncomplicated pregnancies of a low-risk population
      after sonographically identified intact intrauterine pregnancy during the first
      trimester. Transvaginal ultrasounds were given to 2,534 women at between six and
      12 weeks of gestation. Inclusion criteria were a positive fetal cardiac activity
      and no antecedent signs of vaginal bleeding. Gestational age was confirmed by
      measurement of the crown-rump length and/or biparietal diameter (BIP). Patients
      were followed until delivery or up to a fetal loss. The mean fetal loss rate
      between 12 and 28 weeks was 3.86% (n = 99). Fetal loss increased with maternal
      age: fetal loss rate under 20 yr: 2.94% (OR 0.75; CI 0.23-2. 46), 20-24 yr: 3.20%
      (OR 0.77; CI 0.48-1.23), 25-29 yr: 3.39% (OR 0.77; CI 0.50-1.19), 30-34 yr: 3.89%
      (OR 1.01; CI 0.59-1.71), 35-39 yr: 7.82% (OR 2.13; CI 1.04-4.32), 40-45 y: 50%
      (OR 13.84; CI 6.67-28.72) and > 45 yr: 50% (OR 13.05; CI 1.96-86.71)
      respectively. The frequency of spontaneous fetal loss before 28 weeks gestation
      was assessed systematically in a low-risk population. There was a very clear
      correlation with advancing maternal age. These data now can be used as background
      loss rate information for evaluating the safety of invasive prenatal diagnosis,
      and they will be more valid for this purpose than the available data taken from
      selected cohorts of women, such as those from hospital clinics or from
      infertility programs.

PMID- 11298369
TI  - Patient with trisomy 6 mosaicism.
AB  - Trisomy 6 and trisomy 6 mosaicism were found in chorionic villi cell culture and
      short term incubation in a prenatal diagnosis at 12 weeks of gestation in a
      pregnancy with a growth retarded fetus showing nuchal translucency. The child was
      born in the 25th gestational week with a number of malformations including heart
      defects, deep-set ears, cleft right hand, cutaneous syndactylies, and overlapping
      toes of irregular shape and length. Trisomy 6 was not found in peripheral blood
      lymphocytes but was confirmed in umbilical cord fibroblasts. Currently, at the
      age of 2-3/4 years, the development of the child is relatively normal despite
      considerable growth delay. At the age of two years, she developed a papular
      erythema clinically suggestive of epidermal nevi. Cytogenetic analysis of
      fibroblast cultures derived from skin from a right hand finger and the inguinal
      area confirmed the presence of a trisomy 6 mosaicism. This is the first
      observation of a liveborn with trisomy 6 mosaicism.

PMID- 11298371
TI  - Problems in the diagnosis of fragile X syndrome in young children are still
      present.
AB  - Fragile X syndrome is common; its prevalence approaches 1 per 5,000. Fragile X
      syndrome is the most common inherited cause of mental retardation. Many
      professionals must deal with fragile X individuals on a daily basis. However,
      despite the diverse information on the epidemiology, clinical features, unique
      pattern of inheritance, cytogenetic, and molecular diagnosis and scales for the
      diagnosis of this syndrome, the diagnosis of fragile X syndrome is still not
      always made by the patients' specialists. Here we present the difficulties in the
      diagnosis of fragile X syndrome in 11 children under 8 years of age, 10 boys and
      one girl. We report data on initial symptoms, behavioral features, and physical
      and mental development before molecular studies were considered. The possible
      causes for the diagnosis delay were multiple: nonspecific features (e.g.,
      macrocephaly, overgrowth, obesity), unremarkable physical examination, family
      history apparently noncontributory, and lack of or delayed molecular testing.
      Careful clinical examination of young children and DNA screening in case of
      doubt, and education of professionals in medical specialty areas, behavioral
      sciences, education, and other fields are recommended.

PMID- 11298372
TI  - Identification of WASP mutations in 14 Spanish families with Wiskott-Aldrich
      syndrome.
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency caused by
      mutations in the WASP gene. The disease is known to be associated with extensive
      clinical variability, and mutation studies indicate that genotypes are also
      highly variant among WAS patients. In this study, we performed mutation analysis
      of the WASP gene in 14 unrelated Spanish families by single strand conformation
      analysis (SSCA) and sequencing, resulting in the identification of a novel
      mutation and nine known mutations. No mutation was identified in one family. The
      ten different mutations include point mutations resulting in amino acid
      substitutions, stop codons, and small deletions and insertions causing
      frameshifts. Missense mutations were preferentially located in the amino-terminal
      part of the protein, exons 2 and 4, whereas stop and frameshift mutations were
      located in the carboxyl-terminal region, exons 10 and 11. However, in two
      families, two missense mutations in exon 11 were identified. Our study
      demonstrates that WASP genotypes have some concordance with the patients'
      phenotypes, although mutation 1019delC, identified in a family with several
      affected members, resulted in high intrafamilial clinical variability.

PMID- 11298373
TI  - Infantile systemic hyalinosis in siblings: clinical report, biochemical and
      ultrastructural findings, and review of the literature.
AB  - A boy presented at age 3.5 months with joint contractures, restlessness, and pain
      on handling. His skin was thickened and there were livid-red macular lesions over
      bony prominences. Infantile systemic hyalinosis (ISH) was diagnosed, a presumably
      autosomal recessive, progressive, and painful disorder of as yet unknown
      pathogenesis. Observation over three years confirmed the diagnosis as typical
      changes, such as nodules on both ears, pearly papules in the perinasal folds and
      on the neck, fleshy nodules in the perianal region, and gingival hypertrophy,
      developed. Skin lesions and painful joint contractures progressed in spite of
      intense physiotherapy, and at age 3, the child had marked motor disability. The
      central nervous system (CNS) appeared to be intact and the infant showed normal
      mental development. Radiologic findings included marked generalized osteopenia,
      osteolytic erosions in the metaphyses of the long bones, and cortical thinning.
      Electron microscopy of two skin biopsies demonstrated deposition of floccular
      amorphous substance that was abundant around, and appeared to originate from,
      small blood vessels in the dermis, partially interfering with collagen fiber
      formation. Lysosomal inclusions were not seen. Serum acid hyaluronidase activity
      was within the normal range, and the synthesis of hyaluronic acid and
      proteoglycans in cultured skin fibroblasts was similar to that of control cells.
      A younger sister presented at age two months with painful joint contractures and
      discrete livid-red macules over both malleoli, and showed a similar progression
      of the disorder over the first year of life. The diagnosis of ISH should be
      considered in infants and children presenting with painful joint contractures and
      skin lesions. The pathogenesis of this disabling and disfiguring disorder remains
      unclear. Our data confirm probable autosomal recessive inheritance, and do not
      support lysosomal storage, hyaluronidase deficiency, or a primary collagen
      disorder, but indicate that the amorphous material accumulating in the skin and
      articular soft tissues may originate from the blood circulation.

PMID- 11298374
TI  - Relationship between the G894T polymorphism (Glu298Asp variant) in endothelial
      nitric oxide synthase and nitric oxide-mediated endothelial function in human
      atherosclerosis.
AB  - Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), plays
      important roles in normal vascular homeostasis, and reduced endothelial NO
      bioactivity is an important feature of vascular disease states. The Glu298Asp
      (G894T) polymorphic variant of eNOS has been associated with vascular disease,
      but functional data are lacking. Accordingly, we examined the relationships
      between NO-mediated endothelial function, the presence of the eNOS Glu298Asp
      variant, and clinical risk factors for atherosclerosis. Endothelium-dependent
      vasorelaxations to different agonists were determined in human saphenous veins
      obtained from patients with coronary artery disease and identified risk factors
      (n = 104). Patients were genotyped for the eNOS G894T polymorphism. Nitric oxide
      mediated endothelial vasorelaxations were highly variable between patients.
      Reduced vasorelaxations were associated with increased number of clinical risk
      factors for atherosclerosis (r = - 0.54, P < 0.001), whereas the Glu298Asp
      variant was not associated with any differences in contractions to phenylephrine,
      NO-mediated vasorelaxations to acetylcholine, bradykinin or calcium ionophore, or
      relaxations to the NO donor sodium nitroprusside. Increased atherosclerotic risk
      factors, but not the presence of the eNOS Glu298Asp variant, are associated with
      impaired nitric oxide-mediated endothelial vasomotor function, suggesting that
      this polymorphism does not have a major direct functional effect on vascular eNOS
      activity in human atherosclerosis.

PMID- 11298375
TI  - del (9p) syndrome: proposed behavior phenotype.
AB  - Over recent years interest in the study of behavior phenotypes has gained
      increasing momentum. We present three white female patients, age respectively 9
      years 9 months, 14 years 6 months and 18 years at the time of the last
      observation, seen because of developmental delay/mental retardation, seizures and
      learning disabilities. Cytogenetic analysis showed a de novo deletion of the
      short arm of chromosome 9 in all three, with the breakpoint being located at band
      9p22. Although several studies have described the somatic phenotype, analytical
      evaluation of verbal and non-verbal cognitive functions are lacking. Our patients
      received a detailed neuropsychological and linguistic evaluation that showed a
      particular behavior profile, in the context of mental retardation of variable
      degree. On selective tests there was a marked deficit in visuo-praxic and visuo
      spatial skills associated with memory disturbance. Visuo-motor integration
      abilities [VMI; Beery, 1997] and visuo-perceptual and visuo-spatial abilities
      [Benton line orientation test, 1992] seemed particularly impaired, both in
      relation to verbal mental age (vocabulary and grammatical
      production/comprehension) and to some non-verbal competencies [Benton face
      recognition test, 1992]. The profile shows advanced performances in face
      recognition. In addition, there is also a dissociation between verbal and visuo
      spatial short term memory. This behavior phenotype is similar to that of Williams
      syndrome (WS) individuals. Our patients also showed some unusual within-domain
      dissociations regarding linguistic abilities. To better demonstrate similarities
      and differences between the behavior phenotypes of the del (9p22) syndrome and
      WS, we studied three IQ-gender-matched WS subjects. The comparison between the
      cognitive phenotypes of the two syndromes shows similarities in
      neuropsychological pattern. We hypothesize that there is a gene within the 9p22
      region responsible for the neuropsychological profile described here.

PMID- 11298376
TI  - Deficiency of the specific granule proteins, R-binder/transcobalamin I and
      lactoferrin, in plasma and saliva: a new disorder.
AB  - The mechanisms of hereditary deficiency of R binder, which originates in
      neutrophils and exocrine gland epithelium, are unknown and may be multiple. This
      led us to examine if defective R binder synthesis also involves proteins that
      colocalize with it in neutrophil-specific granules and exocrine epithelial cells
      and may be under common regulatory control. Stored plasma and saliva samples from
      five unrelated R binder-deficient patients and control subjects were assayed for
      R binder, lactoferrin, cationic antimicrobial protein-18, neutrophil gelatinase
      associated lipocalin, gelatinase, lysozyme, and myeloperoxidase. One patient,
      patient A, had lactoferrin levels below the limits of detection in both plasma
      and saliva in addition to his R binder deficiency. Although his deficiency
      involved lactoferrin as well, he had no history of predisposition to infection.
      PCR amplification of his R binder gene promoter region and the beginning of the
      first exon revealed no DNA abnormalities. His son and the son of his equally
      deficient brother, both presumptive heterozygotes, had mild deficiency of both R
      binder and lactoferrin. The results show that R binder deficiency exists in at
      least two forms. One, presumably the less common of the two forms, is the new
      hereditary entity described here, which is characterized by deficiency of more
      than one specific granule protein in both plasma and saliva. Despite this more
      widely distributed absence of the proteins than is found in congenital specific
      granule deficiency, infection posed no clinical problem in the affected patient.

PMID- 11298377
TI  - Dandy-Walker variant in Coffin-Siris syndrome.
AB  - We describe a five-month-old male infant with Coffin-Siris syndrome, the so
      called Dandy-Walker variant (hypoplasia of the cerebellar vermis with cystic
      dilatation of the fourth ventricle, but without enlargement of the posterior
      fossa), and partial agenesis of the corpus callosum. Dandy-Walker malformation
      and mega cisterna magna, but not Dandy-Walker variant, have been reported in
      Coffin-Siris syndrome. The presence of Dandy-Walker variant in the infant we
      described confirms that the full continuum of the Dandy-Walker complex can occur
      in Coffin-Siris syndrome. The yet unidentified gene(s) for the syndrome may be
      related to the development of the hindbrain.

PMID- 11298378
TI  - Cranial and hand skeleton in fragile X syndrome.
AB  - The purpose of the present study was to track prenatally observed skeletal
      deviations in radiographs from fragile X syndrome children and young adults in a
      search for improvement of early diagnostics of fragile X syndrome. The material
      consisted of craniofacial profile radiographs and hand radiographs from six males
      age between 2 years 9 months and 20 years 3 months. Craniofacial radiographs
      showed normal morphology of the nasal bone in all cases. In five cases the sella
      turcica could be analyzed. In two cases the anterior wall of the sella was
      oblique, and in two cases the dorsum sellae appeared short. In one case the sella
      turcica had normal structure. In two cases, the cervical column was suitable for
      examination. In one, body fusion and short arcus occurred. Of the six hand
      radiographs analyzed, the hand skeleton appeared normal in the youngest male. In
      the other five cases there was a deviant location of the carpal bones in the
      developmental field corresponding to the first finger. Skeletal maturity was
      delayed in all cases. In conclusion, the prenatally registered morphological
      deviations in the skeletal development of fragile X syndrome fetuses were found
      in 5 of 6 fragile X males and young adults. We suggest that a skeletal analysis
      be considered in the phenotypic classification of children with fragile X
      syndrome.

PMID- 11298379
TI  - DHCR7 genotypes of cousins with Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of
      cholesterol biosynthesis caused by mutations of the 7-dehydrocholesterol
      reductase gene (DHCR7). We report on three cousins with SLOS, all of whom were
      found to be compound heterozygotes for the common splice site mutation IVS8-1G-
      >C and the missense mutation T289I. DNA analysis of one set of parents
      demonstrated that the father carried the missense mutation and the mother carried
      the IVS8-1G-->C mutation. By extension, the two unrelated mothers were both
      heterozygous for IVS8-1G-->C. This finding supports the notion of a high carrier
      frequency of the IVS8-1G-->C null mutation in Northern European Caucasians.

PMID- 11298380
TI  - A man, a syndrome, a gene: Clouston's hidrotic ectodermal dysplasia (HED).
AB  - This paper presents a biographical sketch of Dr. H. R. Clouston, whose eponym is
      attached to a type of hidrotic ectodermal dystrophy, and a brief account of the
      mapping of the gene and its identification as the connexin gene, GJB6.

PMID- 11298381
TI  - A genetic risk calculation surprise.

PMID- 11298382
TI  - Kabuki syndrome in a Haitian patient.

PMID- 11298383
TI  - Effects of 5 s exposures to a 50 microT, 20 Hz magnetic field on skin conductance
      and ratings of affect and arousal.
AB  - This study investigated the effect of a weak magnetic field (50 microT, 20 Hz
      sinusoidal, 5 s duration) on concurrent perceptions of visual stimuli. Subjects
      were seated between Helmholtz coils and gave post-exposure ratings for the
      affective content and arousing nature of presented images. They were blind as to
      the presence or absence of a simultaneously presented field. Skin conductance and
      arousal ratings did not show significant differences between experimental and
      control conditions, but the affective content rating did (P = 0.041), with the
      images viewed under field exposure being rated as having a more positive affect.
      Such measures might thus be useful as additional indicators of magnetic field
      detection. A post-hoc analysis of skin conductance profiles showed that 48% of
      subjects exhibited a lowering of skin conductance during field exposure, 34%
      exhibited no apparent reaction, and 17% exhibited an increase. Overall ratings
      given by each of the groups appeared to relate to these physiological profiles.

PMID- 11298384
TI  - Calculation of electric fields induced in the human knee by a coil applicator.
AB  - Calculations are presented of the induced electric fields and current densities
      in the cartilage of the knee produced by a coil applicator developed for applying
      pulsed magnetic fields to osteoarthritic knees. This applicator produces a
      sawtooth-like magnetic field waveform composed of a series of 260-micros pulses
      with a peak to peak magnitude of approximately 0.12 mT in the cartilage region.
      The simulations were performed using a recently developed 3 dimensional finite
      difference frequency domain technique for solving Maxwell's equations with an
      equivalent circuit model. The tissue model was obtained from the anatomically
      segmented human body model of Gandhi. The temporal peak electric field magnitude
      was found to be -153 mV/m, averaged within the medial cartilage of the knee for
      the typical dB/dt excitation levels of this coil. The technique can be extended
      to analyze other excitation waveforms and applicator designs.

PMID- 11298385
TI  - Measuring temporal variability in residential magnetic field exposures.
AB  - Considerable interest has developed during the past ten years regarding the
      hypothesis that living organisms may respond to temporal variability in ELF
      magnetic fields to which they are exposed. Consequently, methods to measure
      various aspects of temporal variability are of interest. In this paper, five
      measures of temporal variability were examined: Arithmetic means (D(mean)) and
      rms values (D(rms)) of the first differences (i.e., absolute value of the
      difference between consecutive measurements) of magnetic field recordings;
      "standardized" forms of D(rms), denoted RCMS, obtained by dividing D(rms) by the
      standard deviations of the magnetic field data; and mean (F(mean)) and rms
      (F(rms)) values of fractional first differences. Theoretical investigations
      showed that D(mean) and D(rms) are virtually unaffected by long-term systematic
      trends (changes) in exposure. These measures thus provide rather specific
      measures of short-term temporal variability. This was also true to a lesser
      extent for F(mean) and F(rms). In contrast, the RCMS metric was affected by both
      short-term and long-term exposure variabilities. The metrics were also
      investigated using a data set consisting of twice-repeated two-calendar-day
      recordings of bedroom magnetic fields and personal exposures of 203 women
      residing in the western portion of Washington State. The predominant source of
      short-term temporal variability in magnetic field exposures arose from the
      movement of subjects through spatially varying magnetic fields. Spearman
      correlations between TWA bedroom magnetic fields or TWA personal exposures and
      five measures of temporal variability were relatively low. Weak to moderate
      levels of correlation were observed between temporal variability measured during
      two different sessions separated in time by 3 or 6 months. We conclude that first
      difference and fractional difference metrics provide specific and fairly
      independent measures of short-term temporal variability. The RCMS metric does not
      provide an easily interpreted measure of short-term or long-term temporal
      variability. This last result raises uncertainties about the interpretation of
      published studies that use the RCMS metric.

PMID- 11298386
TI  - Partial-body exposure of human volunteers to 2450 MHz pulsed or CW fields
      provokes similar thermoregulatory responses.
AB  - Many reports describe data showing that continuous wave (CW) and pulsed (PW)
      radiofrequency (RF) fields, at the same frequency and average power density (PD),
      yield similar response changes in the exposed organism. During whole-body
      exposure of squirrel monkeys at 2450 MHz CW and PW fields, heat production and
      heat loss responses were nearly identical. To explore this question in humans, we
      exposed two different groups of volunteers to 2450 MHz CW (two females, five
      males) and PW (65 micros pulse width, 10(4) pps; three females, three males) RF
      fields. We measured thermophysiological responses of heat production and heat
      loss (esophageal and six skin temperatures, metabolic heat production, local skin
      blood flow, and local sweat rate) under a standardized protocol (30 min baseline,
      45 min RF or sham exposure, 10 min baseline), conducted in three ambient
      temperatures (T(a) = 24, 28, and 31 degrees C). At each T(a), average PDs studied
      were 0, 27, and 35 mW/cm2 (Specific absorption rate (SAR) = 0, 5.94, and 7.7
      W/kg). Mean data for each group showed minimal changes in core temperature and
      metabolic heat production for all test conditions and no reliable differences
      between CW and PW exposure. Local skin temperatures showed similar trends for CW
      and PW exposure that were PD-dependent; only the skin temperature of the upper
      back (facing the antenna) showed a reliably greater increase (P =.005) during PW
      exposure than during CW exposure. Local sweat rate and skin blood flow were both
      T(a)- and PD-dependent and showed greater variability than other measures between
      CW and PW exposures; this variability was attributable primarily to the
      characteristics of the two subject groups. With one noted exception, no clear
      evidence for a differential response to CW and PW fields was found.

PMID- 11298388
TI  - Growth and differentiation of PC6 cells: the effects of pulsed electromagnetic
      fields (PEMF).
AB  - Previous studies in our laboratory showed that neurite outgrowth in vitro and
      nerve regeneration in vivo were stimulated by 2 Hz, 0.3 mT (3 G) pulsed
      electromagnetic fields (PEMF). To learn more about the effects of PEMF on nerve
      cells, we exposed PC6 cells, a standard neuronal-like cell model, to the same
      pulsed electromagnetic fields for 2 h/day for 2 days and asked whether two
      different cell processes, proliferation and differentiation, were affected. The
      cells were also treated with a differentiating agent, nerve growth factor (NGF),
      to further define any interactive effects. We found that proliferation was
      unaffected by either PEMF or NGF alone or in combination. Differentiation,
      expressed as neurite outgrowth, was strongly upregulated with NGF, but this NGF
      response was significantly depressed in cells treated with PEMF.

PMID- 11298387
TI  - Effects of high ELF magnetic fields on enzyme-catalyzed DNA and RNA synthesis in
      vitro and on a cell-free DNA mismatch repair.
AB  - Environmental electromagnetic fields have been implicated in human cancers. We
      examined whether high extremely low frequency (ELF) AC magnetic fields could
      affect DNA synthesis, transcription or repair, using in vitro model systems with
      defined sequences. The rate and fidelity of DNA polymerase catalyzed DNA
      synthesis, as well as of RNA polymerase catalyzed RNA synthesis, were not
      statistically significantly affected by 60 Hz 0.25-0.5 Tesla magnetic fields. The
      efficiency of mutS dependent mismatch repair with human cell extracts was also
      not affected by the magnetic field exposure. The results suggest that the core
      processes related to the transmission of genetic information are stable under
      high ELF magnetic fields.

PMID- 11298389
TI  - Dielectric response of some biological tissues.
AB  - The dielectric properties of two freshly excised mice tissue samples (kidney,
      skeletal muscle) and also freshly excised Ehrlich solid tumor were measured in
      the frequency range from 20 Hz to 100 kHz using RLC bridges. The data were fitted
      to a summation of multiple Cole-Cole dispersion and also to the constant power
      law which is related formally to the fractal geometries of tissues using a
      genetic algorithm for optimization developed by the author. The data were in good
      agreement with the Cole-Cole equation for the three samples.

PMID- 11298390
TI  - No effects of pulsed radio frequency electromagnetic fields on melatonin,
      cortisol, and selected markers of the immune system in man.
AB  - There is growing public concern that radio frequency electromagnetic fields may
      have adverse biological effects. In the present study eight healthy male students
      were tested to see whether or not radio frequency electromagnetic fields as used
      in modern digital wireless telecommunication (GSM standard) have noticeable
      effects on salivary melatonin, cortisol, neopterin, and immunoglobulin A (sIgA)
      levels during and several hours after exposure. In a specifically designed,
      shielded experimental chamber, the circularly polarized electromagnetic field
      applied was transmitted by an antenna positioned 10 cm behind the head of upright
      sitting test persons. The carrier frequency of 900 MHz was pulsed with 217 Hz
      (average power flux density 1 W/m2). In double blind trials, each test person
      underwent a total of 20 randomly allotted 4 hour periods of exposure and sham
      exposure, equally distributed at day and night. The results obtained show that
      the salivary concentrations of melatonin, cortisol, neopterin and sIgA did not
      differ significantly between exposure and sham exposure.

PMID- 11298391
TI  - Millimeter wave power density in aqueous biological samples.
AB  - Power density distribution inside a water sample placed between two parallel
      lossy dielectric plates (Polystyrene) was calculated using Fresnel equations for
      the frequency range of 42.25-53.57 GHz. Due to the multiple internal reflections
      from the sample boundaries, the distribution of the power density within the thin
      sample is more uniform than that within a semi-infinite medium. The power density
      in a sample depends on the thicknesses of the sample and the adjacent dielectric
      plates. For the given frequency range the sample thickness optimal for power
      density uniformity varies between 0.28 and 0.33 mm. The front plate has a
      significant effect on the magnitude of the power density within the sample but
      little effect on the power density distribution. The thicker the rear plate, the
      greater is the non uniformity of the power density distribution within the
      sample. Based on the calculated data, we determined the dimension of an exposure
      chamber providing the optimal power density distribution uniformity for mm-wave
      irradiation.

PMID- 11298393
TI  - An absence of angst.

PMID- 11298392
TI  - The proteome isn't genome II.

PMID- 11298394
TI  - Museum visitors take priority as Smithsonian curbs research.

PMID- 11298397
TI  - PubMed Central offers deal on content.

PMID- 11298398
TI  - Funding battle heats up over large array.

PMID- 11298396
TI  - Restrictions delay fossil hunts in Ethiopia.

PMID- 11298399
TI  - Biologists bugged by space station cuts and uncertainties.

PMID- 11298400
TI  - Report fudges issue as South Africa fights on against HIV.

PMID- 11298402
TI  - Bush favours research at Pentagon and NIH.

PMID- 11298404
TI  - Is it all just a pipe dream?

PMID- 11298405
TI  - Making crops cry for help.

PMID- 11298406
TI  - Silicon philanthropists follow a great tradition.

PMID- 11298407
TI  - When DNA research menaces diversity.

PMID- 11298408
TI  - Gulf syndrome research has passed peer review.

PMID- 11298409
TI  - PubMed Central decentralized.

PMID- 11298410
TI  - Science for the have-nots.

PMID- 11298421
TI  - Being objective.

PMID- 11298422
TI  - Moving rhythms.

PMID- 11298423
TI  - Pop-up disaster.

PMID- 11298424
TI  - Reproductive biology. Out with a bang.

PMID- 11298425
TI  - Condensed-matter physics. An expanding view of plutonium.

PMID- 11298426
TI  - Biological catalysis. The hairpin's turn.

PMID- 11298428
TI  - Physiology. A hunger for cannabinoids.

PMID- 11298429
TI  - Global change. A piece in the CO2 jigsaw.

PMID- 11298430
TI  - Cell cycle. Checking two steps.

PMID- 11298432
TI  - Obituary. Claude Shannon (1916-2001).

PMID- 11298433
TI  - Herculaneum victims of Vesuvius in ad 79.

PMID- 11298434
TI  - High-speed swimming. Enhanced power in yellowfin tuna.

PMID- 11298436
TI  - Neanderthal DNA. Not just old but old and cold?

PMID- 11298435
TI  - Environment. Superselective clay for radium uptake.

PMID- 11298438
TI  - The role of chaotic resonances in the Solar System.
AB  - Our understanding of the Solar System has been revolutionized over the past
      decade by the finding that the orbits of the planets are inherently chaotic. In
      extreme cases, chaotic motions can change the relative positions of the planets
      around stars, and even eject a planet from a system. Moreover, the spin axis of a
      planet-Earth's spin axis regulates our seasons-may evolve chaotically, with
      adverse effects on the climates of otherwise biologically interesting planets.
      Some of the recently discovered extrasolar planetary systems contain multiple
      planets, and it is likely that some of these are chaotic as well.

PMID- 11298439
TI  - Crystal structure of a hairpin ribozyme-inhibitor complex with implications for
      catalysis.
AB  - The hairpin ribozyme catalyses sequence-specific cleavage of RNA. The active site
      of this natural RNA results from the docking of two irregular helices: stems A
      and B. One strand of stem A harbours the scissile bond. The 2.4 A resolution
      structure of a hairpin ribozyme-inhibitor complex reveals that the ribozyme
      aligns the 2'-OH nucleophile and the 5'-oxo leaving group by twisting apart the
      nucleotides that flank the scissile phosphate. The base of the nucleotide
      preceding the cleavage site is stacked within stem A; the next nucleotide, a
      conserved guanine, is extruded from stem A and accommodated by a highly
      complementary pocket in the minor groove of stem B. Metal ions are absent from
      the active site. The bases of four conserved purines are positioned potentially
      to serve as acid-base catalysts. This is the first structure determination of a
      fully assembled ribozyme active site that catalyses a phosphodiester cleavage
      without recourse to metal ions.

PMID- 11298440
TI  - An auroral flare at Jupiter.
AB  - Jupiter's aurora is the most powerful in the Solar System. It is powered largely
      by energy extracted from planetary rotation, although there seems also to be a
      contribution from the solar wind. This contrasts with Earth's aurora, which is
      generated through the interaction of the solar wind with the magnetosphere. The
      major features of Jupiter's aurora (based on far-ultraviolet, near-infrared and
      visible-wavelength observations) include a main oval that generally corotates
      with the planet and a region of patchy, diffuse emission inside the oval on
      Jupiter's dusk side. Here we report the discovery of a rapidly evolving, very
      bright and localized emission poleward of the northern main oval, in a region
      connected magnetically to Jupiter's outer magnetosphere. The intensity of the
      emission increased by a factor of 30 within 70 s, and then decreased on a similar
      timescale, all captured during a single four-minute exposure. This type of
      flaring emission has not previously been reported for Jupiter (similar, but
      smaller, transient events have been observed at Earth), and it may be related
      directly to changes in the solar wind.

PMID- 11298441
TI  - Quantum computing in molecular magnets.
AB  - Shor and Grover demonstrated that a quantum computer can outperform any classical
      computer in factoring numbers and in searching a database by exploiting the
      parallelism of quantum mechanics. Whereas Shor's algorithm requires both
      superposition and entanglement of a many-particle system, the superposition of
      single-particle quantum states is sufficient for Grover's algorithm. Recently,
      the latter has been successfully implemented using Rydberg atoms. Here we propose
      an implementation of Grover's algorithm that uses molecular magnets, which are
      solid-state systems with a large spin; their spin eigenstates make them natural
      candidates for single-particle systems. We show theoretically that molecular
      magnets can be used to build dense and efficient memory devices based on the
      Grover algorithm. In particular, one single crystal can serve as a storage unit
      of a dynamic random access memory device. Fast electron spin resonance pulses can
      be used to decode and read out stored numbers of up to 105, with access times as
      short as 10-10 seconds. We show that our proposal should be feasible using the
      molecular magnets Fe8 and Mn12.

PMID- 11298442
TI  - Correlated electrons in delta-plutonium within a dynamical mean-field picture.
AB  - Given the practical importance of metallic plutonium, there is considerable
      interest in understanding its fundamental properties. Plutonium undergoes a 25
      per cent increase in volume when transformed from its alpha-phase (which is
      stable below 400 K) to the delta-phase (stable at around 600 K), an effect that
      is crucial for issues of long-term storage and disposal. It has long been
      suspected that this unique property is a consequence of the special location of
      plutonium in the periodic table, on the border between the light and heavy
      actinides-here, electron wave-particle duality (or itinerant versus localized
      behaviour) is important. This situation has resisted previous theoretical
      treatment. Here we report an electronic structure method, based on dynamical mean
      field theory, that enables interpolation between the band-like and atomic-like
      behaviour of the electron. Our approach enables us to study the phase diagram of
      plutonium, by providing access to the energetics and one-electron spectra of
      strongly correlated systems. We explain the origin of the volume expansion
      between the alpha- and delta-phases, predict the existence of a strong
      quasiparticle peak near the Fermi level and give a new viewpoint on the physics
      of plutonium, in which the alpha- and delta-phases are on opposite sides of the
      interaction-driven localization-delocalization transition.

PMID- 11298443
TI  - Optical polymer thin films with isotropic and anisotropic nano-corrugated surface
      topologies.
AB  - Light reflection from computer monitors, car dashboards and any other optical
      surface can impair the legibility of displays, degrade transmission of optical
      components and in some cases may even pose safety hazards. Antireflective
      coatings are therefore widely used, but existing antireflection technologies
      often perform sub-optimally or are expensive to implement. Here we present an
      alternative approach to antireflection coatings, based on an extension of our
      photo-aligning and photo-patterning technology for liquid-crystal displays (LCDs)
      and liquid-crystal polymer films with smooth surfaces to optical polymer films
      with controlled surface topologies. Nano- and micro-corrugated topologies are
      shown to result from optically induced monomer phase-separation on the polymer
      surfaces. The properties of the resulting films make them suitable high
      performance and low-cost antireflection coatings for optical components of
      virtually any size, shape and material. Moreover, the approach can be used to
      form a wide range of other functional polymer thin films with isotropic as well
      as anisotropic topologies. For example, films can be produced whose optical
      birefringence exceeds that of the birefringence of the polymer material itself.
      These new films can also be used as diffractive thin films, diffusers, and
      directional reflectors which preserve light polarization, or as substrates for
      aligning liquid crystals to produce bright, low-power-consumption LCDs with
      integrated optical functions and memory.

PMID- 11298444
TI  - Removal of chlorofluorocarbons by increased mass exchange between the
      stratosphere and troposphere in a changing climate.
AB  - Chlorofluorocarbons (CFCs), along with bromine compounds, have been unequivocally
      identified as being responsible for most of the anthropogenic destruction of
      stratospheric ozone. With curbs on emissions of these substances, the recovery of
      the ozone layer will depend on their removal from the atmosphere. As CFCs have no
      significant tropospheric removal process, but are rapidly photolysed above the
      lower stratosphere, the timescale for their removal is set mainly by the rate at
      which air is transported from the troposphere into the stratosphere. Using a
      global climate model we predict that, in response to the projected changes in
      greenhouse-gas concentrations during the first half of the twenty-first century,
      this rate of mass exchange will increase by 3% per decade. This increase is due
      to more vigorous extra-tropical planetary waves emanating from the troposphere.
      We estimate that this increase in mass exchange will accelerate the removal of
      CFCs to an extent that recovery to levels currently predicted for 2050 and 2080
      will occur 5 and 10 years earlier, respectively.

PMID- 11298445
TI  - Control of cation concentrations in stream waters by surface soil processes in an
      Amazonian watershed.
AB  - The chemical composition of ground waters and stream waters is thought to be
      determined primarily by weathering of parent rock. In relatively young soils such
      as those occurring in most temperate ecosystems, dissolution of primary minerals
      by carbonic acid is the predominant weathering pathway that liberates Ca2+, Mg2+
      and K+ and generates alkalinity in the hydrosphere. But control of water
      chemistry in old and highly weathered soils that have lost reservoirs of primary
      minerals (a common feature of many tropical soils) is less well understood. Here
      we present soil and water chemistry data from a 10,000-hectare watershed on
      highly weathered soil in the Brazilian Amazon. Streamwater cation concentrations
      and alkalinity are positively correlated to each other and to streamwater
      discharge, suggesting that cations and bicarbonate are mainly flushed from
      surface soil layers by rainfall rather than being the products of deep soil
      weathering carried by groundwater flow. These patterns contrast with the seasonal
      patterns widely recognized in temperate ecosystems with less strongly weathered
      soils. In this particular watershed, partial forest clearing and burning 30 years
      previously enriched the soils in cations and so may have increased the observed
      wet season leaching of cations. Nevertheless, annual inputs and outputs of
      cations from the watershed are low and nearly balanced, and thus soil cations
      from forest burning will remain available for forest regrowth over the next few
      decades. Our observations suggest that increased root and microbial respiration
      during the wet season generates CO2 that drives cation-bicarbonate leaching,
      resulting in a biologically mediated process of surface soil exchange controlling
      the streamwater inputs of cations and alkalinity from these highly weathered
      soils.

PMID- 11298446
TI  - Plateau 'pop-up' in the great 1897 Assam earthquake.
AB  - The great Assam earthquake of 12 June 1897 reduced to rubble all masonry
      buildings within a region of northeastern India roughly the size of England, and
      was felt over an area exceeding that of the great 1755 Lisbon earthquake.
      Hitherto it was believed that rupture occurred on a north-dipping Himalayan
      thrust fault propagating south of Bhutan. But here we show that the northern edge
      of the Shillong plateau rose violently by at least 11 m during the Assam
      earthquake, and that this was due to the rupture of a buried reverse fault
      approximately 110 km in length and dipping steeply away from the Himalaya. The
      stress drop implied by the rupture geometry and the prodigious fault slip of 18
      +/- 7 m explains epicentral accelerations observed to exceed 1g vertically and
      surface velocities exceeding 3 m s-1 (ref. 1). This quantitative observation of
      active deformation of a 'pop-up' structure confirms that faults bounding such
      structures can penetrate the whole crust. Plateau uplift in the past 2-5 million
      years has caused the Indian plate to contract locally by 4 +/- 2 mm yr-1,
      reducing seismic risk in Bhutan but increasing the risk in northern Bangladesh.

PMID- 11298447
TI  - Plant diversity enhances ecosystem responses to elevated CO2 and nitrogen
      deposition.
AB  - Human actions are causing declines in plant biodiversity, increases in
      atmospheric CO2 concentrations and increases in nitrogen deposition; however, the
      interactive effects of these factors on ecosystem processes are unknown. Reduced
      biodiversity has raised numerous concerns, including the possibility that
      ecosystem functioning may be affected negatively, which might be particularly
      important in the face of other global changes. Here we present results of a
      grassland field experiment in Minnesota, USA, that tests the hypothesis that
      plant diversity and composition influence the enhancement of biomass and carbon
      acquisition in ecosystems subjected to elevated atmospheric CO2 concentrations
      and nitrogen deposition. The study experimentally controlled plant diversity (1,
      4, 9 or 16 species), soil nitrogen (unamended versus deposition of 4 g of
      nitrogen per m2 per yr) and atmospheric CO2 concentrations using free-air CO2
      enrichment (ambient, 368 micromol mol-1, versus elevated, 560 micromol mol-1). We
      found that the enhanced biomass accumulation in response to elevated levels of
      CO2 or nitrogen, or their combination, is less in species-poor than in species
      rich assemblages.

PMID- 11298448
TI  - Chemical speciation drives hydrothermal vent ecology.
AB  - The physiology and biochemistry of many taxa inhabiting deep-sea hydrothermal
      vents have been elucidated; however, the physicochemical factors controlling the
      distribution of these organisms at a given vent site remain an enigma after 20
      years of research. The chemical speciation of particular elements has been
      suggested as key to controlling biological community structure in these extreme
      aquatic environments. Implementation of electrochemical technology has allowed us
      to make in situ measurements of chemical speciation at vents located at the East
      Pacific Rise (9 degrees 50' N) and on a scale relevant to the biology. Here we
      report that significant differences in oxygen, iron and sulphur speciation
      strongly correlate with the distribution of specific taxa in different
      microhabitats. In higher temperature (> 30 degrees C) microhabitats, the
      appreciable formation of soluble iron-sulphide molecular clusters markedly
      reduces the availability of free H2S/HS- to vent (micro)organisms, thus
      controlling the available habitat.

PMID- 11298449
TI  - Perceiving visual expansion without optic flow.
AB  - When an observer moves forward in the environment, the image on his or her retina
      expands. The rate of this expansion conveys information about the observer's
      speed and the time to collision. Psychophysical and physiological studies have
      provided abundant evidence that these expansionary motions are processed by
      specialized mechanisms in mammalian visual systems. It is commonly assumed that
      the rate of expansion is estimated from the divergence of the optic-flow field
      (the two-dimensional field of local translational velocities). But this rate
      might also be estimated from changes in the size (or scale) of image features. To
      determine whether human vision uses such scale-change information, we have
      synthesized stochastic texture stimuli in which the scale of image elements
      increases gradually over time, while the optic-flow pattern is random. Here we
      show, using these stimuli, that observers can estimate expansion rates from scale
      change information alone, and that pure scale changes can produce motion after
      effects. These two findings suggest that the visual system contains mechanisms
      that are explicitly sensitive to changes in scale.

PMID- 11298450
TI  - The motor side of depth vision.
AB  - To achieve stereoscopic vision, the brain must search for corresponding image
      features on the two retinas. As long as the eyes stay still, corresponding
      features are confined to narrow bands called epipolar lines. But when the eyes
      change position, the epipolar lines migrate on the retinas. To find the matching
      features, the brain must either search different retinal bands depending on
      current eye position, or search retina-fixed zones that are large enough to cover
      all usual locations of the epipolar lines. Here we show, using a new type of
      stereogram in which the depth image vanishes at certain gaze elevations, that the
      search zones are retina-fixed. This being the case, motor control acquires a
      crucial function in depth vision: we show that the eyes twist about their lines
      of sight in a way that reduces the motion of the epipolar lines, allowing
      stereopsis to get by with smaller search zones and thereby lightening its
      computational load.

PMID- 11298451
TI  - Leptin-regulated endocannabinoids are involved in maintaining food intake.
AB  - Leptin is the primary signal through which the hypothalamus senses nutritional
      state and modulates food intake and energy balance. Leptin reduces food intake by
      upregulating anorexigenic (appetite-reducing) neuropeptides, such as alpha
      melanocyte-stimulating hormone, and downregulating orexigenic (appetite
      stimulating) factors, primarily neuropeptide Y. Genetic defects in anorexigenic
      signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors,
      cause obesity. However, alternative orexigenic pathways maintain food intake in
      mice deficient in neuropeptide Y. CB1 cannabinoid receptors and the
      endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the
      hypothalamus, and marijuana and anandamide stimulate food intake. Here we show
      that following temporary food restriction, CB1 receptor knockout mice eat less
      than their wild-type littermates, and the CB1 antagonist SR141716A reduces food
      intake in wild-type but not knockout mice. Furthermore, defective leptin
      signalling is associated with elevated hypothalamic, but not cerebellar, levels
      of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin
      treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl
      glycerol in the hypothalamus. These findings indicate that endocannabinoids in
      the hypothalamus may tonically activate CB1 receptors to maintain food intake and
      form part of the neural circuitry regulated by leptin.

PMID- 11298452
TI  - Induction of the mammalian node requires Arkadia function in the extraembryonic
      lineages.
AB  - The early mammalian embryo is patterned by signals emanating from extraembryonic
      and embryonic signalling centres, most notably the anterior visceral endoderm
      (AVE) and the node, respectively. The AVE is responsible for anterior
      development, whereas further axis specification depends on the node, the
      equivalent of Spemann's organizer. Formation of the node, at the anterior
      primitive streak, depends on expression of the transcription factor HNF3beta
      (ref. 4). However, both the source and the nature of the signals responsible for
      inducing the node have been unknown. Here we describe a recessive lethal
      mutation, arkadia, generated using gene-trap mutagenesis. Mutant embryos
      establish an AVE but fail to maintain anterior embryonic structures and lack a
      node. The mutation has disrupted the Arkadia gene, which encodes a putative
      intracellular protein containing a RING domain. Arkadia is essential for HNF3beta
      expression in the anterior primitive streak. Analysis with chimaeras, however,
      shows that Arkadia functions within extraembryonic tissues, revealing that these
      are required to induce the node. Furthermore, our experiments show that Arkadia
      interacts genetically with the transforming growth factor (TGF)beta-like factor
      Nodal, implying that Nodal mediates the function of Arkadia in node induction.

PMID- 11298453
TI  - Arkadia enhances nodal-related signalling to induce mesendoderm.
AB  - Nodal-related members of the transforming growth factor (TGF)-beta family
      regulate the induction of mesoderm, endoderm, and mesendoderm, a tissue specific
      to the Spemann organizer. How these different tissues form in response to the
      same signalling molecules is not completely understood. It has been suggested
      that concentration-dependent effects, mediated by extracellular cofactors and
      antagonists, are responsible for the differences. Here we show that the nuclear
      protein Arkadia specifically potentiates the mesendoderm-inducing activity of a
      subset of TGF-beta family members. The combined activities of Arkadia and Xenopus
      nodal-related-1 are sufficient to induce mesendoderm and suppress mesoderm.
      Arkadia dorsalizes ventral tissues, resulting in the induction of organizer
      specific gene expression. Blocking nodal signalling extracellularly inhibits
      these effects. Arkadia influences nodal activity when co-expressed and can
      function in cells adjacent to those producing the nodal signal. Our findings,
      together with the observation that Arkadia mutant mice lack a node and node
      derived mesendoderm, identify Arkadia as an essential modulator of the nodal
      signalling cascade that leads to induction of Spemann's organizer.

PMID- 11298454
TI  - HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential
      mechanism for protecting the infected host cell.
AB  - In vivo infection of lymphatic tissues by the human immunodeficiency virus type 1
      (HIV-1) leads to enhanced apoptosis, which prominently involves uninfected
      bystander cells. Increased killing of such bystander cells is mediated in part
      through Nef induction of Fas ligand (FasL) expression on the surface of the
      virally infected T cells. The subsequent interaction of FasL with Fas (CD95)
      displayed on neighbouring cells, including HIV-1-specific cytotoxic T
      lymphocytes, may lead to bystander cell killing and thus forms an important
      mechanism of immune evasion. As HIV-1 also enhances Fas expression on virally
      infected cells, it is unclear how these hosts avoid rapid cell-autonomous
      apoptosis mediated through cis ligation of Fas by FasL. Here we show that HIV-1
      Nef associates with and inhibits apoptosis signal-regulating kinase 1 (ASK1), a
      serine/threonine kinase that forms a common and key signalling intermediate in
      the Fas and tumour-necrosis factor-alpha (TNFalpha) death-signalling pathways.
      The interaction of Nef with ASK1 inhibits both Fas- and TNFalpha-mediated
      apoptosis, as well as the activation of the downstream c-Jun amino-terminal
      kinase. Our findings reveal a strategy by which HIV-1 Nef promotes the killing of
      bystander cells through the induction of FasL, while simultaneously protecting
      the HIV-1-infected host cell from these same pro-apoptotic signals through its
      interference with ASK1 function.

PMID- 11298455
TI  - A superfamily of variant genes encoded in the subtelomeric region of Plasmodium
      vivax.
AB  - The malarial parasite Plasmodium vivax causes disease in humans, including
      chronic infections and recurrent relapses, but the course of infection is rarely
      fatal, unlike that caused by Plasmodium falciparum. To investigate differences in
      pathogenicity between P. vivax and P. falciparum, we have compared the
      subtelomeric domains in the DNA of these parasites. In P. falciparum,
      subtelomeric domains are conserved and contain ordered arrays of members of
      multigene families, such as var, rif and stevor, encoding virulence determinants
      of cytoadhesion and antigenic variation. Here we identify, through the analysis
      of a continuous 155,711-base-pair sequence of a P. vivax chromosome end, a
      multigene family called vir, which is specific to P. vivax. The vir genes are
      present at about 600-1,000 copies per haploid genome and encode proteins that are
      immunovariant in natural infections, indicating that they may have a functional
      role in establishing chronic infection through antigenic variation.

PMID- 11298456
TI  - The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA
      synthesis.
AB  - When exposed to ionizing radiation (IR), eukaryotic cells activate checkpoint
      pathways to delay the progression of the cell cycle. Defects in the IR-induced S
      phase checkpoint cause 'radioresistant DNA synthesis', a phenomenon that has been
      identified in cancer-prone patients suffering from ataxia-telangiectasia, a
      disease caused by mutations in the ATM gene. The Cdc25A phosphatase activates the
      cyclin-dependent kinase 2 (Cdk2) needed for DNA synthesis, but becomes degraded
      in response to DNA damage or stalled replication. Here we report a functional
      link between ATM, the checkpoint signalling kinase Chk2/Cds1 (Chk2) and Cdc25A,
      and implicate this mechanism in controlling the S-phase checkpoint. We show that
      IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated
      phosphorylation of Cdc25A on serine 123. An IR-induced loss of Cdc25A protein
      prevents dephosphorylation of Cdk2 and leads to a transient blockade of DNA
      replication. We also show that tumour-associated Chk2 alleles cannot bind or
      phosphorylate Cdc25A, and that cells expressing these Chk2 alleles, elevated
      Cdc25A or a Cdk2 mutant unable to undergo inhibitory phosphorylation (Cdk2AF)
      fail to inhibit DNA synthesis when irradiated. These results support Chk2 as a
      candidate tumour suppressor, and identify the ATM-Chk2-Cdc25A-Cdk2 pathway as a
      genomic integrity checkpoint that prevents radioresistant DNA synthesis.

PMID- 11298461
TI  - Publication and promotion: call for breaking the link.

PMID- 11298462
TI  - Singular anti-RNA virus-directed proteins.
AB  - AIMS: To additionally purify and characterise the anti-RNA virus-directed protein
      termed p14. MATERIALS AND METHODS: Antiviral assays of p14 against RNA and DNA
      viruses were carried out and its antigenic similarities with chicken interferon
      (CIFN) were studied. HPLC-Reverse Phase of p14 was performed to further purify
      p14. RESULTS: p14 showed antiviral activity against RNA viruses only and not
      against DNA viruses. It was antigenically distinct from CIFN. Purification of p14
      yielded three proteins with antiviral activity, which had different physico
      chemical properties than those described for interferons. CONCLUSIONS: The data
      presented on the antiviral, immunological and physico-chemical properties,
      establish the unique nature of p14 vis-a-vis those of interferons.

PMID- 11298463
TI  - Putrescine, DNA, RNA and protein contents in human uterine, breast and rectal
      cancer.
AB  - AIMS: To find out the status of DNA, RNA and protein in human uterine, ovarian,
      breast and rectal carcinoma. MATERIAL AND METHODS: In this prospective study,
      patients of age group between late thirties and late fifties suffering from
      uterine, ovarian, breast and rectal cancer were taken as subjects of the present
      study. The total number of cases studied for each cases was ten. Pieces of human
      carcinomatous tissues of above mentioned cases were taken along with surrounding
      normal tissues. From the tissue samples, putrescine is separated by the method of
      Herbst et al, DNA analysed by Diphenylamine method, RNA by Orcinol method and
      protein by Biuret method. RESULTS: Tissue content of putrescine rises
      simultaneously with that of DNA, RNA and protein in carcinomatous growths as
      above in comparison to their respective adjacent normal tissue, the differences
      being statistically highly significant. CONCLUSIONS: Increase in DNA, RNA and
      protein concentration may be a pre-requisite for increased synthesis of
      putrescine in carcinomatous tissue and thereby the concentration of other di- and
      poly-amines.

PMID- 11298464
TI  - Indomethacin therapy in hydramnios.
AB  - AIM: The use of indomethacin in treatment of hydramnios was evaluated. SUBJECTS &
      METHODS: Twelve patients with symptomatic hydramnios were treated with
      indomethacin (2.2- 3.0 mg/kg body weight/day). RESULTS: The treatment was started
      at a gestational age of 31.17-/+7.94 weeks and continued for 3.74-/+2.3 weeks.
      Eleven patients responded to the therapy both subjectively and objectively and
      pregnancies were prolonged by 4.6-/+3.1 weeks (range 0.1-10 weeks). Five women
      had term deliveries. Six patients had a favourable perinatal outcome. Four
      patients who had a known congenital anomaly in the foetus, delivered stillborn
      babies or had an early neonatal death. One patient who did not follow up after
      commencing therapy delivered a full-term stillbirth. One patient delivered within
      1 day of starting therapy. Indomethacin therapy caused no maternal complications.
      CONCLUSION: Indomethacin was effective in the management of hydramnios and
      preventing it's complications.

PMID- 11298466
TI  - Progressive systemic sclerosis (scleroderma), carcinoma breast and valvular heart
      disease: an unusual combination.
AB  - Systemic sclerosis is a multi system disorder characterised by fibrosis of skin
      and internal organs. There are reports of relation between cancer and
      polymyositis/dermatomyositis, but no overall association with systemic sclerosis.
      Reports of the coexistence of cancer and systemic sclerosis, however, emphasise a
      close temporal relation in their occurrence. Cardiac involvement in the form of
      myocardial fibrosis and pericarditis occurs frequently in systemic sclerosis,
      while valvular involvement has been reported only sporadically. We report a
      patient, admitted for adenocarcinoma of left breast who was found to have
      features of systemic sclerosis, pulmonary hypertension, gangrene of toes, and
      stenotic mitral valve disease. The possible mechanisms of the coincidence of the
      three disorders are discussed.

PMID- 11298465
TI  - Hypomagnesaemia in paediatric population in an intensive care unit.
AB  - AIMS: To determine incidence and risk factors for hypomagnesaemia in children
      admitted in Paediatric Intensive Care Unit, (PICU). SUBJECTS AND METHODS:
      Prospective study was carried out on 80 children admitted in PICU. The patients
      were clinically assessed for nutritional status, neurological status on Glasgow
      coma scale, congestive cardiac failure, etc. and relevant biochemical parameters
      including serum and red cell magnesium levels were done. 25 patients of the same
      age group admitted in general ward who were not in critical state were included
      as a control group. RESULTS: 70% of PICU patients had hypomagnesaemia, which was
      more common in patients on aminoglycosides and diuretics. CONCLUSION: In view of
      complications of magnesium depletion and benign nature of appropriate magnesium
      therapy critically ill children should have their magnesium level monitored.

PMID- 11298467
TI  - Nephritis and cerebellar ataxia: rare presenting features of enteric fever.
AB  - Enteric fever is a common infectious disease of the tropical world, about 80% of
      these cases occur in Asian countries. Enteric fever presenting with isolated
      cerebellar ataxia or nephritis is rare. We report three cases of enteric fever
      that presented with these complications. Isolated cerebellar ataxia usually
      occurs in the second week, whereas in our cases it presented within first four
      days of fever. The common complications of enteric fever related to the urinary
      tract are cystitis, pyelitis, and pyelonephritis. Glomerulonephritis is uncommon.
      Most patients with enteric glomerulonephritis present with acute renal failure,
      hypertensive encephalopathy, or nephritic syndrome. In comparison, our case had
      milder manifestations. All three patients were treated with parenteral
      ceftriaxone and showed a prompt recovery.

PMID- 11298468
TI  - Waldenstrom's macroglobulinaemia with intracerebral haemorrhage.
AB  - A 65-year-old male was admitted for evaluation of severe anaemia, recurrent
      epistaxis, axillary lymphadenopathy, and hepatomegaly. The diagnosis of
      Waldenstrom's macroglobulinaemia was made on the basis of clinical and laboratory
      findings. The patient developed intracerebral haemorrhage without associated
      hypertension and with normal coagulation profile.

PMID- 11298469
TI  - Jejunal obstruction and perforation resulting from herniation through broad
      ligament.
AB  - Internal herniation of small bowel through broad ligament causing obstruction is
      rare. A case of jejunal herniation through broad ligament defect with resultant
      obstruction and perforation is presented.

PMID- 11298470
TI  - Ruptured true aneurysm of the splenic artery: an unusual cause of
      haemoperitoneum.
AB  - True aneurysm of the splenic artery is rare. Two cases of ruptured true splenic
      artery aneurysms are presented. The first patient was a 62-year-old female who
      presented within 6 hours of the onset of symptoms. The other was a 27-year-old
      non-alcoholic male patient who was admitted in a state of shock after 2 days of
      observation in a peripheral hospital. Both patients had haemoperitoneum and were
      subjected to exploratory laparotomy. Aneurysmectomy was performed in both the
      patients in addition to left splenopancreatectomy in the first case and
      splenectomy in the second. However, due to the prolonged preoperative shock, the
      second patient succumbed on the third postoperative day.

PMID- 11298471
TI  - The art and science of presentation: electronic presentations.

PMID- 11298472
TI  - Clinical patient record systems architecture: an overview.

PMID- 11298473
TI  - Authorship: rules, rights, responsibilities and recommendations.

PMID- 11298474
TI  - Primary extra-nodal non-Hodgkin's lymphoma of the cheek.

PMID- 11298475
TI  - Endovascular glue embolisation of intercostal arteriovenous fistula: a non
      surgical treatment option.

PMID- 11298476
TI  - Functioning oxyphil adenoma of parathyroid.

PMID- 11298477
TI  - Committee on Publication Ethics (COPE). Guidelines on good publication practice.

PMID- 11298478
TI  - Vertigo and vestibular rehabilitation.
AB  - The role of rehabilitation in the management of vertigo is limited to a very
      specific group of conditions. An Occupational therapist who is a part of the
      multidisciplinary team treating the vertiginous patient, with the knowledge of
      physiology and therapeutic benefit of vestibular rehabilitation can widen the
      rehabilitation spectrum for various diseases producing vertigo and
      dysequilibrium, to resolve or minimise these symptoms. The present article
      reviews the need for vestibular rehabilitation and the different conditions
      needing the same along with its characteristics, physiology and various exercises
      prescribed.

PMID- 11298479
TI  - Mitochondrial diseases: an overview of genetics, pathogenesis, clinical features
      and an approach to diagnosis and treatment.
AB  - Defects in structures or functions of mitochondria, mainly involving the
      oxidative phosphorylation, mitochondrial biogenesis and other metabolic pathways
      have been shown to be associated with a wide spectrum of clinical phenotypes. The
      ubiquitous nature of mitochondria and their unique genetic features contribute to
      the clinical, biochemical and genetic heterogenecity of mitochondrial diseases.
      This article focuses on the recent advances in the field of mitochondrial
      disorders with respect to the consequences for an advanced clinical and genetic
      diagnostics. In addition, an overview on recently identified genetic defects and
      their pathogenic molecular mechanisms are given.

PMID- 11298480
TI  - National Institute of Cholera and Enteric Diseases.

PMID- 11298481
TI  - Paediatrics in India.

PMID- 11298482
TI  - Atorvastatin: in the management of hyperlipidaemia.

PMID- 11298483
TI  - 'Mantle of safety'--aero-medical service in Central Australia.

PMID- 11298484
TI  - Imiquimod applied topically: A novel immune response modifier.
AB  - Imiquimod (S-26308, R-837) (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4
      amine), and immune response modifier, was approved as a 5% cream (Aldara, 3M
      Pharmaceuticals) by the US FDA in February 1997, for the treatment of genital and
      perianal warts. Drug activity results primarily from induction of interferon
      alpha (IFN-alpha) and other cytokines in the skin, which stimulate several other
      aspects of the innate immune response. Imiquimod also stimulates acquired
      immunity, in particular the cellular arm, which is important for control of viral
      infections and tumors. It is expected to be effective where exogenous IFN-alpha
      has shown utility, and where enhancement of cell-mediated immunity is needed.
      Recently presented Phase II clinical studies demonstrated efficacy in treating UV
      induced skin lesions, basal cell carcinoma, and actinic keratosis. Case studies
      have reported benefit when treating molluscum and in prevention of keloids after
      surgery.

PMID- 11298485
TI  - Genes that cause smoking?

PMID- 11298486
TI  - By the way, doctor...I'm a woman, age 52 and generally healthy. But sometimes my
      urine has blood in it. After doing some tests, my doctor has pretty much ruled
      out a urinary tract infection, which makes sense to me because I haven't had any
      burning sensation. They've done an ultrasound but haven't found anything. I have
      an appointment to see a urologist, who is going to look inside my bladder. Should
      I be worried about cancer or something serious like that?

PMID- 11298487
TI  - Therapeutic relevance of altered cytokine expression.
AB  - Cytokines and their receptors have numerous physiological functions. Altered
      concentrations of these mediators are associated with various afflictions. For
      example, over-expression of cytokines has been associated with altered drug
      concentrations and activity. Greater concentrations of cardiovascular drugs have
      been observed in humans and laboratory animals with various types of inflammatory
      disorders compared to healthy controls. Interestingly, the observed higher
      concentrations of drugs such as propranolol and verapamil have not been
      associated with increased effects. Indeed, reduced response to these
      cardiovascular drugs is observed, suggestive of cytokine-mediated downregulation
      of receptors. Increased cytokine concentrations have also been associated with
      decreased response to drugs used in treatment of other disorders such as AIDS,
      asthma and psychiatric diseases. This reduced response to drug in the presence of
      altered cytokine concentrations is especially relevant to the elderly population
      which has a greater incidence of multiple diseases and elevated concentrations of
      various cytokines compared to younger individuals. Furthermore, inflammatory
      conditions and their accompanied increased over-expression of cytokines are
      suggested to be the main determinants of therapeutic failure in myocardial
      infarction and angina. Therefore, altered cytokine concentrations may influence
      therapeutic outcomes of pharmacotherapy and result in treatment failure.

PMID- 11298488
TI  - The role of tumour necrosis factor-alpha in the pathogenesis of complicated
      falciparum malaria.
AB  - Plasmodium falciparum malaria is the most important parasitic infection of humans
      and is one of the most serious health problems facing the inhabitants of
      developing countries. It is responsible for about 2 million deaths every year. To
      date there is no specific treatment for the disease apart from anti-malarials.
      The declining sensitivity to these drugs is a serious therapeutic problem, while
      no safe and effective vaccine is likely to be available for general use in the
      near future. There is now abundant laboratory and clinical evidence to suggest
      that tumour necrosis factor-alpha (TNF-alpha) plays a major role in the
      pathogenesis of complicated falciparum malaria. Modulation of TNF-alpha response
      in combination with the current anti-malarial drugs, may represent a novel
      approach to the treatment of the serious complications associated with the
      disease.

PMID- 11298489
TI  - Caveolae and clathrin-coated vesicles: two possible internalization pathways for
      IFN-gamma and IFN-gamma receptor.
AB  - Interferon-gamma (IFN-gamma) elicits a variety of activities following binding to
      its cell-surface-specific receptor (IFN-gammaR). This complex formation leads to
      the activation of the Jak-STAT pathway. Several hypotheses have been proposed to
      explain the role and location of the receptor and its ligand in the signalling
      pathway. In vivo as well as in vitro, the present study shows that IFN-gamma and
      its receptor were internalized in different cellular compartments including
      cytoplasmic matrix, mitochondria and nucleus. In order to analyse the
      internalization pathway of IFN-gamma and its receptor, we have study in vivo and
      in vitro their colocalization with clathrin and caveolin by using double
      immunogold-labelling experiments using electron microscopy. We demonstrate that
      IFN-gamma and IFN-gammaR were colocalized in the caveolin-containing structures
      and the clathrin-coated pits suggesting that both internalization pathways may be
      used. This indicates that IFN-gamma and IFN-gammaR were internalized by these two
      different pathways, suggesting two different intracellular routes probably for
      different target cell-compartments.

PMID- 11298490
TI  - Expression and functional analysis of chemokine receptors in human peripheral
      blood leukocyte populations.
AB  - Emerging evidence indicates that chemokine receptor expression patterns are
      critical in determining the spectrum of action of the chemokines. We have
      analysed the expression patterns of 17 chemokine receptors and two orphan
      chemokine receptor-like genes in various freshly prepared human peripheral blood
      leucocyte populations, including neutrophils, lymphocytes, and naive and
      differentiated monocytes using real-time quantitative polymerase chain reaction
      (TaqMan). This is the first comprehensive study of chemokine receptor expression
      in such a wide variety of cell types. Human peripheral blood leukocyte
      populations were found to express a wide range of chemokine receptors that varies
      depending on cell type and differentiation state. Novel expression patterns of
      certain chemokine receptors were seen during our analysis. For example, the
      orphan chemokine receptor HCR was expressed at very high levels by both primary
      neutrophils and primary monocytes, and was further upregulated on neutrophil
      activation and during monocyte to macrophage differentiation. When neutrophil
      calcium transients were measured in response to a panel of 30 different
      chemokines the results clearly correlated with the chemokine receptor expression
      profile. For example strong calcium responses were seen in neutrophils following
      stimulation with the CXCR1 and CXCR2 ligands, interleukin (IL-)8, GCP-2 and Gro
      beta. These data have implications for the study of the functional responses of
      leukocytes to external stimuli and will aid in our understanding of general
      leukocyte biology.

PMID- 11298491
TI  - IL-10 mediation of activation-induced TH1 cell apoptosis and lymphoid dysfunction
      in polymicrobial sepsis.
AB  - Recent studies suggest that increased activation-induced lymphocyte apoptosis
      (AICD) is detected in mouse splenocytes during polymicrobial sepsis which may
      contribute to lymphocyte immune dysfunction [i.e., decreased interleukin (IL-)2
      and interferon-gamma (IFN-gamma) production] leading to the associated morbidity
      seen in those animals. Thus, we wanted to examine the hypothesis that immune
      suppressive agents, such as IL-4, IL-10 or prostaglandin E2(PGE2), known to be
      elevated in septic animals, also contribute to this increase in AICD. Here we
      demonstrate that the inclusion of monoclonal antibody (mAb) to IL-10, but not
      anti-IL-4 or ibuprofen (IBU), blunted this sepsis induced increase in splenocyte
      AICD. Additionally, septic mice deficient in the IL-10 gene product (-/-) showed
      neither an increase in AICD nor a loss of IL-2/IFN-gamma release capacity.
      Interestingly, mAb to IL-10 did not altered the extent of AICD in a Th2-cell
      line, but exogenous IL-10 did potentiate Th1-like cell line AICD. This was
      consistent with the finding that the increased AICD seen in septic mouse
      splenocytes was restricted largely to the CD4+ cells producing IL-2 (Th1-cells)
      and that mAb to IL-10 treatment suppressed this change. Furthermore, IL-10
      appears to mediate its AICD effect by upregulation of the Fas receptor and Fas
      receptor signaling protein components, but not by altered expression of
      Bcl/Bax/Bad family members, in septic mouse splenocytes. To the extent that these
      processes contribute in a pathological fashion to the animal's capacity to
      survive sepsis we have previously observed that in vivo post-treatment of mice
      with mAb IL-10 markedly attenuated septic mortality. Collectively, these data
      indicate that in the septic mouse the Th2 cytokine IL-10 not only serves to
      actively induce Th1 lymphocyte immune dysfunction but also plays a role in their
      apoptotic depletion. These processes in turn appear to contribute to the animal's
      inability to ward off lethal septic challenge.

PMID- 11298492
TI  - Glycyrrhizin restores the impaired IL-12 production in thermally injured mice.
AB  - Mice 6 days after thermal injury (TI-mice) did not respond to lipopolysaccharide
      (LPS) stimulation for production of serum interleukin 12 (IL-12; 2 h after LPS
      stimulation, <20 pg/ml in TI-mice; 1091+/-162 pg/ml in normal mice). However, 2 h
      after LPS stimulation, 1456+/-118 pg/ml of IL-12 were demonstrated in sera of TI
      mice previously treated with a 10 mg/kg i.p. dose of glycyrrhizin (GR). IL-12 was
      not induced by LPS in sera of normal mice inoculated with burn-associated type 2
      T cells (IL-4/IL-10-producing CD8+CD11b+TCRgamma/delta+T cells isolated from
      spleens of TI-mice). However, IL-12 production was induced by LPS in sera of
      these mice previously treated with GR or a mixture of monoclonal antibodies
      (mAbs) for type 2 cytokines. Also, IL-12 production was induced by LPS in TI-mice
      inoculated with CD4+T cells from spleens of GR-treated normal mice (GR-CD4+T
      cells, 5x10(6)cells/mouse). Since GR-CD4+T cells have been shown to be
      antagonistic cells against production of type 2 cytokines by burn-associated type
      2 T cells, these results indicate that IL-12 unresponsiveness shown in TI-mice is
      recovered by GR through the regulation of burn-associated type 2 T cell
      responses.

PMID- 11298493
TI  - Complex effects of interferon-alpha on the cytokine network in HIV infection-
      possible contribution to immunosuppression.
AB  - Since interleukin (IL-)2, IL-10 and IL-12 may contribute to the pathogenesis of
      human immune deficiency virus (HIV) infection we examined the effect of
      interferon (IFN)-alpha on these cytokines in cultures of various subsets of
      peripheral blood mononuclear cells (PBMC) in ten HIV-infected patients and ten
      healthy controls. Our main findings were: (1) IFN-alpha markedly enhanced IL-10
      levels in a dose-dependent manner in both lipopolysaccharide (LPS)- and
      phytohaemagglutinin (PHA)-stimulated PBMC, as well as in anti-CD3- and anti
      CD3/anti-CD28-stimulated T cells in both HIV-infected patients and controls. (2)
      In contrast, IFN-alpha had a downregulatory effect on IL-10 levels in Candida 
      stimulated PBMC,with particularly strong suppressive effect in HIV-infected
      patients. (3) Furthermore, IFN-alpha had a significant but modest stimulatory
      effect on IL-2 levels in PHA- and Candida -stimulated PBMC and anti-CD3
      stimulated T cells. (4) IFN-alpha enhanced IL-12 levels in a dose-dependent
      manner in LPS-stimulated PBMC in both patients and controls. Our findings that
      IFN-alpha markedly enhanced IL-10 and modestly enhanced IL-2 and IL-12, suggest a
      net immunosuppressive effect of IFN-alpha in HIV-infected patients, possibly
      contributing to progression of immunodeficiency in these patients.

PMID- 11298494
TI  - Repeated inhalation exposure to octamethylcyclotetrasiloxane produces
      hepatomegaly, transient hepatic hyperplasia, and sustained hypertrophy in female
      Fischer 344 rats in a manner similar to phenobarbital.
AB  - Octamethylcyclotetrasiloxane (D4) has been described as a phenobarbital-like
      inducer of hepatic enzymes. Phenobarbital (PB) and phenobarbital-like chemicals
      induce transient hepatic and thyroid hyperplasia and sustained hypertrophy in
      rats and mice. The extent to which these processes are involved with D4-induced
      hepatomegaly is not known. The present study has evaluated the effects of
      repeated inhalation exposure to D4 vapors on hepatic and thyroid cell
      proliferation and hypertrophy with respect to time and exposure concentration.
      Female Fischer 344 rats were exposed via whole body inhalation to 0 ppm D4, 700
      ppm D4 vapors (6 h/day; 5 days/week), or 0.05% PB in drinking water over a 4-week
      period. Incorporation of 5'-bromo-2-deoxyuridine (BrdU) and the abundance of
      proliferating cell nuclear antigen were used as indicators of cell proliferation.
      Designated animals from each treatment group were euthanized on study days 6, 13,
      and 27. The effect of D4 exposure concentration on hepatic cell proliferation was
      evaluated at 0, 7, 30, 70, 150, 300, or 700 ppm. Liver-to-body weight ratios in
      animals exposed to 700 ppm D4 were increased 18, 20, and 22% over controls while
      PB-treated animals showed increases of 33, 27, and 27% over controls on days 6,
      13, and 27 respectively. Hepatic incorporation of BrdU following exposure to D4
      was highest on day 6 (labeling index = 15-22%) and was at or below control values
      by day 27. This pattern of transient hyperplasia was observed in all hepatic
      lobes examined and was similar to the pattern observed following treatment with
      PB.

PMID- 11298495
TI  - Trimethyltin-activated cyclooxygenase stimulates tumor necrosis factor-alpha
      release from glial cells through reactive oxygen species.
AB  - Exposure of a primary culture of glial cells to the classical neurotoxicant
      trimethyltin (TMT) results in the release of prostaglandin (PG)E(2) and tumor
      necrosis factor (TNF)-alpha. Prior treatment of glial cells with either the
      nonspecific inhibitor of cyclooxygenase and lypoxygenase eicosatetraynoic acid
      (ETYA) or the cyclooxygenase inhibitor indomethacin completely prevented TMT
      induced PGE(2) production and TNF-alpha release, suggesting a role for
      cyclooxygenase metabolites in TMT-induced TNF-alpha release. Exposure of glial
      cells to increasing concentrations of PGE(2) or other prostanoids did not
      increase TNF-alpha synthesis, while the presence of exogenous PGE(2) during
      treatment of glial cells with TMT actually suppressed TNF-alpha release. The
      activation of arachidonic acid metabolism produces reactive oxygen species (ROS).
      Scavenging of ROS by means of the antioxidant trolox prevented the TMT-induced
      release of TNF-alpha from glial cells, while indomethacin was found to suppress
      ROS formation induced by 1 microM TMT in glial cells. These results suggest that
      activation of arachidonic acid metabolism causes TNF-alpha release through the
      production of ROS rather than PGE(2). Indeed, PGE(2) may exert negative feedback
      on the release of TNF-alpha.

PMID- 11298496
TI  - Lead exposure affects levels of galactolipid metabolic enzymes in the developing
      rat brain.
AB  - Lead poisoning is known to cause myelin defects. Galactolipids are the major
      lipid components of myelin and myelin-competent oligodendrocytes. The present
      study examines the cellular activity of enzymes involved in the galactolipid
      pathway, tissue concentrations of galactolipids, and the cellular activity of
      2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) in rat pups exposed to lead
      in utero and subsequently through maternal milk from exposed mothers and in
      drinking water following weaning. Pups from control and lead-treated groups (500
      or 2000 ppm lead in the drinking water) were euthanized by decapitation on
      postnatal day 7, 14, 21, 35, or 56. Lead decreased levels of galactolipids and
      the oligodendrocyte marker CNPase in the brain to a similar degree. The ratios of
      galactocerebrosides/sulfatides and nonhydroxy fatty acid/hydroxy fatty acid forms
      of the galactolipids were not altered by lead treatment. In contrast, the
      activities of the galactolipid metabolic enzymes were reduced to a degree
      significantly greater than that of CNPase or galactolipids. These results are
      consistent with previously obtained data indicating that in vitro cultured
      oligodendroglial progenitor cells are a target for Pb toxicity. Chronic Pb
      exposure may impact on brain development by impairing timely myelin production
      due to perturbation of the early developmental commitment of oligodendroglial
      progenitors. It is further suggested that perturbation of the galactolipid
      pathway during the developmental maturation of oligodendrocytes may represent a
      contributing mechanism for Pb-induced neurotoxicity.

PMID- 11298497
TI  - Estrogenic activity and metabolism of n-butyl benzyl phthalate in vitro:
      identification of the active molecule(s).
AB  - Some phthalates are suspected to disrupt the endocrine system, especially by
      mimicking estrogens. N-butyl benzyl phthalate (BBP) has estrogenic effects in
      vitro but not in vivo. The aim of this study was to identify the active
      molecule(s) (parent compound and/or metabolite(s)) involved in the estrogenic
      activities of BBP. The estrogenic effects of BBP and its in vivo metabolites were
      assessed using the following tests: E-Screen, ER binding, and PR induction tests
      on the human breast cancer cell line MCF-7 (ER(+)). BBP, the parent compound, was
      a partial agonist. It stimulated MCF-7 proliferation in the E-Screen assay and
      increased cytosolic progesterone receptors (PR) levels in a concentration
      dependent manner. No BBP metabolites were active except hippuric acid (HA), which
      had a weak effect at very high concentrations. BBP and HA stimulatory effects on
      MCF-7 proliferation were antagonized by tamoxifen. However, no competition was
      observed between BBP or HA and 17beta-estradiol for binding to the estrogen
      receptor (ER). BBP metabolism by MCF-7 cells was also investigated. After a 48-h
      incubation, only 10% of the initial BBP remained in the culture medium,
      demonstrating that BBP was extensively metabolized by the MCF-7 cells. The
      radioactivity recovered in the medium was represented by: mono-n-butyl phthalate
      (MBuP, 25%) and mono-n-benzyl phthalate (MBeP, 48%), phthalic acid (6%), and
      benzoic acid (3%). Since none of these metabolites had estrogenic activities,
      this study demonstrates that the parent compound was the active molecule involved
      in the in vitro estrogenic effects of BBP.

PMID- 11298498
TI  - Impairment of alveolar macrophage phagocytosis by ultrafine particles.
AB  - We investigated whether slowed clearance after exposure to ultrafine particles
      was due to a failure in alveolar macrophage phagocytosis. This was achieved by
      measuring the ability of a macrophage cell line (J774.2 MPhi) to phagocytose 2
      microg indicator latex beads following 8-h exposures to a number of test
      particles. Particles utilized were fine titanium dioxide (TiO2), ultrafine
      titanium dioxide (UTiO2), carbon black (CB), or ultrafine carbon black (UCB).
      Cytotoxicity of particles was measured by means of MTT activity. In a preliminary
      study, we assessed the effects of conditioned medium from particle-treated
      macrophages on the phagocytic ability of naive macrophages. Ultrafine and fine
      particles had no significant cytotoxic effects on J774.2 MPhi. A significant
      reduction in the ability of macrophages to phagocytose the indicator beads
      occurred after exposure to 0.39 microg/mm(2) (p < 0.001) of UCB and 0.78
      microg/mm(2) (p < 0.001) of all particle types compared to the control.
      Furthermore, ultrafine particles were shown to significantly (p < 0.001) impair
      macrophage phagocytosis at a lower dose than their fine counterparts (0.39 and
      0.78 microg/mm(2), respectively). At all doses, UCB resulted in a greater number
      (p < 0.001) of nonphagocytic macrophages compared to the other test particles. We
      tested whether a diffusable mediator being released from particle-exposed cells
      inhibited the phagocytic activity of adjacent macrophages. The conditioned medium
      from particle-exposed macrophages had no significant effect on the phagocytic
      ability of macrophages, suggesting that cell-cell contact is responsible for the
      pattern of failed phagocytosis (data not shown). We have demonstrated that
      ultrafine particles impair macrophage phagocytosis to a greater extent than fine
      particles compared on a mass basis. Therefore, we conclude that slowed clearance
      of particles, specifically the ultrafines, can in part be attributed to a
      particle-mediated impairment of macrophage phagocytosis.

PMID- 11298499
TI  - Analysis of the additivity of in vitro inhibition of cholinesterase by mixtures
      of chlorpyrifos-oxon and azinphos-methyl-oxon.
AB  - Organophosphorus (OP) insecticides or their active metabolites act through a
      common mechanism of toxicity, the inhibition of cholinesterase (ChE). The effects
      of in vitro exposure of brain (target) and serum (biomarker) ChE to chlorpyrifos
      oxon (C horizontal lineO) and azinphos-methyl-oxon (AZM horizontal lineO), the
      active metabolites of the insecticides chlorpyrifos and azinphos-methyl,
      respectively, were investigated to determine if simultaneous or sequential
      exposure to these two OP compounds results in purely additive effects. Additive
      was defined by the theoretical calculated percent inhibition (dose additivity),
      which takes into account the fraction of ChE molecules assumed to be available
      for inhibition by the second compound following inhibition by the first compound,
      not simple mathematical summation of percent inhibition (response additivity).
      Brain ChE simultaneously exposed to the two compounds resulted in additive
      effects, which were less than the simple mathematical summation of percent
      inhibition. However, serum ChE simultaneously exposed to the two compounds
      resulted in a nonlinear response, presumably due in part to the presence of
      detoxifying enzymes in the serum. Sequential exposure of both brain and serum ChE
      to the two compounds resulted in greater than additive effects at the higher
      concentrations of each compound. There was no departure from additivity at the
      lower concentrations of the two compounds. These data suggest that simple
      mathematical summation of percent inhibitions, i.e., response additivity, is not
      the appropriate method for describing the combined effects of C horizontal lineO
      and AZM horizontal lineO on ChE in vitro. In addition, there are other mechanisms
      involved, such as the presence of detoxication enzymes, that must be taken into
      account when analyzing the effects of combined exposure of ChE to these two
      compounds.

PMID- 11298501
TI  - Analysis of the toxic effects of linoleic acid, 12,13-cis-epoxyoctadecenoic acid,
      and 12,13-dihydroxyoctadecenoic acid in rabbit renal cortical mitochondria.
AB  - P450 epoxidation of linoleic acid has been associated with many pathological
      conditions that often lead to acute renal failure. However, there is only
      suggestive evidence that linoleic acid monoepoxides and/or linoleic diols
      directly induce mitochondrial dysfunction. Using isolated rabbit renal cortical
      mitochondria (RCM), we found that linoleic acid (50 microM) and the linoleic acid
      monoepoxide, cis-12,13-epoxy-9-octadecenoic acid (12,13-EOA, 50 microM) increased
      state 4 and oligomycin-insensitive respiration and reduced state 3 and oligomycin
      sensitive respiration. Concomitant with these effects, linoleic acid and 12,13
      EOA decreased mitochondrial membrane potential (DeltaPsi). In contrast, the
      hydrolyzed product of 12,13-EOA, 12,13-dihydroxyoctadecenoic acid (12,13-DHOA, 50
      microM), had no effect on state 3, state 4, oligomycin-sensitive, and oligomycin
      insensitive respiration, and DeltaPsi. Neither linoleic acid or its metabolites
      altered uncoupled respiration, which suggests that these compounds have no affect
      on electron transport chain in RCM. Nucleotides such as ATP (0.5 mM) and GDP (0.5
      mM) partially prevented the decrease in DeltaPsi but did not attenuate the
      increase in oligomycin-insensitive respiration after exposure to linoleic acid
      (50 microM) and 12,13-EOA (50 microM). These results demonstrate that linoleic
      acid metabolism to the 12,13-DHOA is a detoxification pathway that prevents
      mitochondrial dysfunction in RCM. The increase in state 4 respiration concomitant
      with decreases in state 3 respiration and DeltaPsi suggest that, in addition to
      uncoupling effects, linoleic acid and 12,13-EOA may have other effects, such as
      alterations of mitochondrial membranes. The inability of ATP and GDP to fully
      attenuate the uncoupling effects of linoleic acid and 12,13-EOA suggests that
      these effects are mediated through a nucleotide-independent mechanism.

PMID- 11298524
TI  - Ascomycin: an advance in the management of atopic dermatitis.

PMID- 11298500
TI  - Zinc tetrakis(N-methyl-4'-pyridyl) porphyrinato is an effective inhibitor of
      stimulant-induced activation of RAW 264.7 cells.
AB  - One proposed mechanism for the development of silica-induced fibrosis is
      prolonged pulmonary inflammation and lung damage resulting from the secretion of
      reactive mediators from alveolar macrophages. Metalloporphyrins have
      antioxidative and antiinflammatory activities. However, the molecular basis for
      the antiinflammatory action of zinc tetrakis(N-methyl-4'-pyridyl) porphyrinato
      (ZnTMPyP) has not been elucidated. The objective of this study was to determine
      whether ZnTMPyP exhibited the ability to inhibit the production of reactive
      oxygen species (ROS), the activation of NF-kappaB, or the secretion of IL-1 in
      RAW 264.7 cells, and whether such inhibitory activity was related to the ROS
      scavenging ability of ZnTMPyP. The results indicate that, although ZnTMPyP is not
      cytotoxic to RAW 264.7 cells, it is a potent inhibitor in ROS production by RAW
      264.7 cells in response to various stimulants, such as silica, zymosan, or
      phorbol myristate acetate. ZnTMPyP is also effective in reducing stimulant
      induced DNA-binding activity of NF-kappaB and silica-induced tyrosine
      phosphorylation of IkappaB-alpha. ZnTMPyP also inhibits LPS-induced IL-1
      production. However, ZnTMPyP exhibits relatively weak ability to directly
      scavenge hyroxyl or superoxide radicals. On the basis of effective concentrations
      of ZnTMPyP, these results suggest that ZnTMPyP directly acts as an inhibitor of
      cellular activation in addition to exhibiting an antioxidant effect. Therefore,
      it is suggested that further studies concerning the effects of ZnTMPyP using in
      vivo oxidative stress models or its effects on the cytotoxic process of human
      diseases associated with lung inflammation and injury are warranted. In addition,
      ZnTMPyP may be a useful tool to investigate the molecular mechanisms involved in
      stimulant-induced signal pathways.

PMID- 11298525
TI  - Mastocytosis: recent advances in defining the disease.
AB  - Mastocytosis is a rare disease characterized by a primary pathological increase
      in mast cells in different tissues, which may present in a variety of clinical
      patterns. Major advances have been made in recent years in the understanding of
      the pathogenesis of mastocytosis. This review is aimed at familiarizing
      dermatologists with these recent findings, and at exploring their possible
      implications for the diagnosis and treatment of the condition. The heterogeneous
      clinical presentation of mastocytosis is detailed with respect to the type of
      skin lesions, age at onset, family history, organ systems involved, associated
      haematological disorders and prognosis. Recent genetic findings also indicate
      different pathogenetic forms of mastocytosis, as adult patients and those with
      associated haematological diseases usually express activating mutations of the
      stem cell factor receptor c-kit, whereas most cases of childhood-onset and
      familial mastocytosis seem to lack these mutations. Despite the presence of c-kit
      mutations, patients with cutaneous lesions generally have a good prognosis, even
      when there is involvement of other organs. Some patients, particularly those with
      childhood-onset disease, experience spontaneous remission, mostly by puberty. c
      kit mutations do not explain the initial cause of mastocytosis, and their
      prognostic significance is as yet unclarified, as is the pathogenesis in patients
      without the mutations. Furthermore, these novel findings have as yet not resulted
      in a more effective treatment of the cause of the disease, so that counselling,
      prevention of exposure to mast cell secretory stimuli, and symptomatic treatment
      remain the mainstays of current patient management.

PMID- 11298526
TI  - Teledermatology: a review.
AB  - Teledermatology holds great potential for revolutionizing the delivery of
      dermatology services, providing equitable service to remote areas and allowing
      primary care physicians to refer patients to dermatology centres of excellence at
      a distance. However, before its routine application as a service tool, its
      reliability, accuracy and cost-effectiveness need to be verified by rigorous
      evaluation. Teledermatology can be applied in one of two ways: it may be
      conducted in real-time, utilizing videoconferencing equipment, or by store-and
      forward methods, when transmitted digital images or photographs are submitted
      with a clinical history. While there is a considerable range of reported accuracy
      and reliability, evidence suggests that teledermatology will become increasingly
      utilized and incorporated into more conventional dermatology service delivery
      systems. Studies to date have generally found that real-time dermatology is
      likely to allow greater clinical information to be obtained from the patient.
      This may result in fewer patients requiring conventional consultations, but it is
      generally more time-consuming and costly to the health service provider. It is
      often favoured by the patient because of the instantaneous nature of the
      diagnosis and management regimen for the condition, and it has educational value
      to the primary care physician. Store-and-forward systems of teledermatology often
      give high levels of diagnostic accuracy, and are cheaper and more convenient for
      the health care provider, but lack the immediacy of patient contact with the
      dermatologist, and involve a delay in obtaining the diagnosis and advice on
      management. It is increasingly likely that teledermatology will prove to be a
      significant tool in the provision of dermatology services in the future. These
      services will probably be provided by store-and-forward digital image systems,
      with real-time videoconferencing being used for case conferences and education.
      However, much more research is needed into the outcomes and limitations of such a
      service and its effect on waiting lists, as well as possible cost benefits for
      patients, primary health care professionals and dermatology departments.

PMID- 11298527
TI  - Management and diagnostic guidelines for urticaria and angio-oedema.
AB  - These guidelines for management of urticaria and angio-oedema have been prepared
      for dermatologists on behalf of the British Association of Dermatologists. They
      present evidence-based guidance for treatment, with identification of the
      strength of evidence available at the time of preparation of the guidelines, and
      a brief overview of aetiology, diagnosis and investigation.

PMID- 11298528
TI  - Exogenous topical lactoferrin inhibits allergen-induced Langerhans cell migration
      and cutaneous inflammation in humans.
AB  - BACKGROUND: Lactoferrin (LF), an iron-binding protein found in exocrine
      secretions, is known to possess antibacterial properties. It has recently been
      proposed that LF may also influence inflammatory reactions. OBJECTIVES: To
      characterize in humans the ability of recombinant homologous LF to inhibit the
      induced migration of epidermal Langerhans cells (LCs) from the skin, a process
      known to be dependent upon the proinflammatory cytokines tumour necrosis factor
      (TNF)-alpha and interleukin 1beta and to influence cutaneous inflammatory
      reactions. METHODS: We investigated the anti-inflammatory properties of LF in
      human volunteers. RESULTS: Topical exposure to LF 2 h prior to sensitization
      caused a significant reduction in contact allergen (diphenylcyclopropenone, DPC)
      induced LC migration from the epidermis as judged by the altered frequency of
      cells expressing either HLA-DR or CD1a determinants. That this reduction was
      secondary to an inhibition of TNF-alpha production was indicated by the fact that
      LF failed to influence LC migration induced by intradermal injection of this
      cytokine. In approximately 50% of those volunteers who displayed local
      inflammation in response to DPC, LF was found to cause a discernible reduction in
      the clinical severity of the reaction, associated with reduced infiltration of
      inflammatory cells. CONCLUSIONS: These data demonstrate that LF is able to
      influence cutaneous immune and inflammatory responses, possibly because of an
      impaired production of local proinflammatory cytokines.

PMID- 11298529
TI  - Diagnosis of autosomal recessive lamellar ichthyosis with mutations in the TGM1
      gene.
AB  - BACKGROUND: Autosomal recessive lamellar ichthyosis (ARLI) is a clinically and
      genetically heterogeneous disorder. In many cases, mutations in the
      transglutaminase 1 gene (TGM1) have been identified, however, other clinically
      indistinguishable cases have been linked to chromosomes 2, 3 and 19. Previous
      studies have failed to establish any correlation between clinical characteristics
      and genetic mutations. OBJECTIVES: To investigate the molecular basis of ARLI in
      10 patients with the typical clinical presentation of the disorder. METHODS: We
      performed polymerase chain reaction and direct sequencing-based mutation
      screening in all of these patients, and TGM1 immunofluorescence microscopy and in
      vitro enzyme activity assays in selected patients. RESULTS: Mutation screening
      revealed 14 mutations, four of which have been previously described. While
      immunofluorescence microscopy was negative in patients with non-sense mutations
      or out-of-frame insertions or deletions, the results were variable in cases with
      mis-sense mutations and in cases with no mutations in the TGM1 gene. In vitro
      enzyme activity assays gave results consistent with the mutation data.
      CONCLUSIONS: Our findings support the importance of mutation screening in the
      evaluation of ARLI.

PMID- 11298530
TI  - Homozygosity at chromosome 8qter in individuals affected by mal de Meleda (Meleda
      disease) originating from the island of Meleda.
AB  - BACKGROUND: The inherited palmoplantar keratodermas (PPKs) are a clinically
      heterogeneous group of disorders characterized by thickening of the skin of the
      palms and the soles. These diseases also exhibit genetic heterogeneity and many
      autosomal dominant and recessive forms have been described. Mal de Meleda (Meleda
      disease, MD) is an autosomal recessive form of PPK first described on the
      Dalmatian island of Meleda. A gene for MD has recently been assigned to the most
      telomeric portion of chromosome 8q using two large Algerian families. OBJECTIVES:
      To determine whether the same gene underlies the skin disease in Meleda
      islanders. METHODS: We have examined five affected individuals originating from
      the Dalmatian island itself for 8qter homozygosity. RESULTS: This region was
      found to be homozygous in all five affected individuals but in none of the 20
      other unaffected family members examined. CONCLUSIONS: The current study confirms
      the localization of a gene for MD to 8qter using samples from the island of
      Meleda, highlighting the clinical and genetic homogeneity of this condition.

PMID- 11298531
TI  - Absence of the t(14;18) chromosomal translocation in primary cutaneous B-cell
      lymphoma.
AB  - BACKGROUND: The t(14;18)(q32;q21) chromosomal translocation is found in the
      majority of nodal follicular lymphomas and in a lower percentage of systemic high
      grade diffuse large B-cell lymphomas. The translocation results in the
      juxtaposition of the bcl-2 gene on chromosome 18 with the immunoglobulin heavy
      chain joining region on chromosome 14. Bcl-2 protein prevents apoptosis and the
      translocation leads to overexpression of a functionally normal Bcl-2 protein that
      prevents apoptosis of neoplastic cells. OBJECTIVES: The purpose of our study was
      to analyse cases of primary cutaneous B-cell lymphoma (PCBCL) for the presence of
      the t(14;18) translocation and to correlate the results with Bcl-2 expression and
      histological subtype. METHODS: Forty-four cutaneous B-cell lymphoid
      proliferations (36 PCBCL, four follicular B-cell lymphomas with cutaneous
      presentation and four reactive B-cell infiltrates) were analysed by polymerase
      chain reaction amplification and polyacrylamide gel electrophoresis using
      consensus primers for the joining region on the immunoglobulin heavy chain gene
      in combination with either a primer for the major breakpoint region (MBR) or the
      minor cluster region (mcr) on chromosome 18. RESULTS: None of 36 PCBCL analysed
      demonstrated a t(14;18) translocation; however, three of four systemic follicular
      B-cell lymphomas presenting in the skin were found to have a translocation in the
      MBR, which was confirmed by sequence analysis. Correlation with Bcl-2
      immunostaining showed that of seven patients with high-grade cutaneous diffuse
      large B-cell lymphoma, four were Bcl-2 positive but had no evidence of a t(14;18)
      translocation. In the five cases classified as primary cutaneous follicle centre
      cell lymphoma, the neoplastic cells within the germinal centres failed to express
      Bcl-2. However, Bcl-2-positive neoplastic cells were present in all four cases of
      systemic follicular lymphoma, including the case that did not show a t(14;18)
      translocation. In all cases of marginal zone lymphoma the marginal zone
      lymphocytes were Bcl-2 positive. CONCLUSIONS: These findings indicate that the
      t(14;18) translocation does not occur in PCBCL, which suggests the involvement of
      different pathogenetic mechanisms compared with their nodal counterparts.
      Furthermore, the detection of a t(14;18) translocation in cutaneous B-cell
      lymphoma should suggest the presence of systemic disease, which underlies the
      need for exhaustive staging procedures.

PMID- 11298532
TI  - Chemotherapy induces or increases expression of multidrug resistance-associated
      protein in malignant melanoma cells.
AB  - BACKGROUND: Human malignant melanoma is notoriously resistant to chemotherapeutic
      agents. Melanoma-derived cell lines are often markedly chemoresistant, suggesting
      that cellular mechanisms mediate generation of the multidrug resistance (MDR)
      phenotype. This phenotype is often due to P-glycoprotein (Pgp) and the MDR
      associated protein (MRP), which are drug transporter proteins associated with
      resistance to a broad spectrum of lipophilic drugs. OBJECTIVES: To determine the
      relationships between the expression of the MDR gene MDR-1 (the product of which
      is Pgp) or the MRP gene, and clinical chemoresistance of malignant melanoma.
      METHODS: We examined changes in the expression of MDR-1 and MRP genes at the mRNA
      level before and after chemotherapy by reverse transcription-polymerase chain
      reaction (RT-PCR) analysis using formalin-fixed, paraffin-embedded sections of 18
      specimens taken from eight melanoma patients. mRNA expression of the MDR-1 and
      MRP gene-specific PCR products was quantitatively determined by densitometry and
      compared with that of an internal standard (beta-actin). RESULTS: Five of seven
      primary melanomas were found to express the MRP gene to a certain extent even
      before chemotherapy. After first and second courses of chemotherapy, six patients
      had an increased ratio of MRP mRNA to beta-actin mRNA compared with the
      prechemotherapy levels in the same patients. None of the cases of melanoma
      expressed MDR-1. CONCLUSIONS: These results suggest that a significant mRNA level
      of MRP gene was intrinsically present in malignant melanoma even before exposure
      to chemotherapeutic drugs and increased in its expression after chemotherapy,
      suggesting that MRP plays a part in increasing the chemoresistance of malignant
      melanoma during chemotherapy.

PMID- 11298533
TI  - Distribution and expression of type VI collagen in photoaged skin.
AB  - BACKGROUND: Several of the characteristic clinical features of photoaged skin,
      including wrinkling, are thought to be dependent on changes in the dermal matrix
      brought about by chronic sun exposure. Such changes include reductions in
      collagens I, III and VII, an increase in elastotic material in the reticular
      dermis and a marked reduction in the microfibrillar glycoprotein fibrillin.
      OBJECTIVES: To examine whether type VI collagen, a microfibrillar collagen
      necessary for cell-cell and cell-matrix communication, is affected by the
      photoageing process. METHODS: Six healthy volunteers with moderate to severe
      photoageing were enrolled into the study. Immunohistochemistry and in situ
      hybridization histochemistry were used to examine the levels of type VI collagen
      in photoprotected and photoaged sites. RESULTS: In photoprotected skin, type VI
      collagen was concentrated in the papillary dermis immediately below the dermal
      epidermal junction, around blood vessels, hair follicles and glandular
      structures. The distribution of type VI collagen was unchanged in photoaged skin,
      although we observed an increase in the abundance of the alpha3 chain of collagen
      VI in the upper papillary dermis, at its junction with the dermal-epidermal
      junction (P < 0.05). No alterations were observed for any alpha chain at the mRNA
      level. CONCLUSIONS: These studies suggest that chronic sun exposure (photoageing)
      has little or no effect on either the distribution, abundance or levels of
      expression of type VI collagen in human skin. Thus, type VI collagen, unlike
      other matrix components so far studied, appears to be relatively unaffected by
      the photoageing process.

PMID- 11298534
TI  - Autoantibodies to the extracellular and intracellular domain of bullous
      pemphigoid 180, the putative key autoantigen in bullous pemphigoid, belong
      predominantly to the IgG1 and IgG4 subclasses.
AB  - BACKGROUND: Autoantibodies to the extracellular domain (ECD) of bullous
      pemphigoid (BP) antigen 180 (BP180) are thought to play a crucial part in the
      pathophysiology of BP. OBJECTIVES: As the various IgG subclasses have different
      biological properties, we have sought to assess the relative isotype distribution
      of IgG to BP180 and their reactivity against the ECD and intracellular domain
      (ICD) of BP180. METHODS: The reactivity of 27 sera from patients with BP was
      assayed by immunoblotting against recombinant proteins covering the ECD and ICD
      of BP180. RESULTS: Twenty-seven (100%) and 21 (77%) of 27 BP sera, respectively,
      contained IgG1 and IgG4 autoantibodies binding to the ECD of BP180. Fourteen
      (82%) and six (35%) of the 17 BP sera that were reactive with the ICD of BP180
      had autoantibodies of the IgG1 and IgG4 subclass, respectively. The profile of
      the isotype restriction appeared to be similar when the response to the ECD vs.
      that to the ICD was compared. IgG2 and IgG3 reactivity with BP180 was found less
      frequently. Patients with BP of longer duration showed a tendency to have, in
      addition to IgG1, an IgG4 response. CONCLUSIONS: Consistent with prior evidence
      indicating that subepidermal blister formation in BP is dependent upon complement
      activation, the frequent finding of complement-fixing IgG1 autoantibodies to both
      the ECD and ICD of BP180 might have pathogenic relevance in BP. These findings
      provide new insights relevant for our understanding of the immune response to
      BP180, the putative key autoantigen in BP.

PMID- 11298535
TI  - Mixed immunobullous disease of childhood: a good response to antimicrobials.
AB  - BACKGROUND: Immunobullous diseases are uncommon in childhood. In contrast to
      adults, the most commonly seen is IgA-mediated chronic bullous disease of
      childhood (CBDC), while IgG-mediated bullous pemphigoid (BP), cicatricial
      pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) are rare. We have
      demonstrated both IgG and IgA autoantibodies to basement membrane zone target
      antigens in eight children with 'mixed immunobullous disease of childhood'.
      OBJECTIVES: To elucidate whether a dual antibody response makes these patients
      distinct regarding their presentation, immunopathology, course and prognosis.
      METHODS: We compared the eight children showing the double antibody response with
      62 children with CBDC, BP, CP and EBA in whom only one antibody isotype was
      demonstrated. Clinical information at presentation, clinical course and response
      to treatment were recorded, and immunoblotting and direct and indirect
      immunofluorescence (IF) were performed. RESULTS: Six of the eight patients
      presented with clinical features of CBDC. In two others, it was uncertain whether
      they had CBDC or BP. Seven of the eight demonstrated a dual antibody response on
      indirect IF and three on direct IF. Immunoblotting revealed a variety of
      epidermal and dermal target antigens (BP230, BP180, 97-kDa protein and laminin
      5). Five of the eight responded well to dapsone, two to sulphonamides, and one to
      systemic erythromycin alone. The clinical course was not protracted. Five are in
      remission 1-4 years following treatment, and three still have active disease
      suppressed by treatment after 6 months-2 years. CONCLUSIONS: Although we do not
      know why these children have 'mixed immunobullous disease' (the dual antibody
      response), our results indicate that the presence of IgA is associated with a
      good response to treatment with antimicrobials (dapsone, sulphonamides,
      erythromycin), and the clinical course is no more protracted than that found in
      children with a single antibody response.

PMID- 11298536
TI  - The severity of cutaneous and oral pemphigus is related to desmoglein 1 and 3
      antibody levels.
AB  - BACKGROUND: Pemphigus vulgaris (PV) and foliaceus (PF) are characterized by
      antibodies to the desmosomal proteins desmoglein 3 (Dsg3) and desmoglein 1
      (Dsg1), respectively. Past studies using indirect immunofluorescence (IIF) as a
      measure of pemphigus antibody levels have failed to demonstrate consistently a
      relationship between disease severity and IIF titres. However, IIF is not able to
      measure separately Dsg1 and 3 antibodies, unlike enzyme-linked immunosorbent
      assays (ELISA), which utilize recombinant proteins. OBJECTIVES: To compare
      independently Dsg1 and 3 antibody levels with the severity of both cutaneous and
      oral involvement in PV and PF. Patients and methods Four hundred and twenty-four
      serum samples were analysed from 80 subjects with PV and 24 with PF. IgG
      antibodies to Dsg1 and 3 were measured by ELISA. For every sample analysed, the
      associated severity of skin and oral disease were graded from 0 to 3; quiescent,
      mild, moderate and severe. RESULTS: A relationship between Dsg1 antibodies and
      skin severity was demonstrated such that a 10-unit increase in Dsg1 ELISA value
      was associated with a 34% chance of having a higher severity score [95%
      confidence interval (CI), 25-45%, P < 0.0005]. This was observed in both PV and
      PF. Oral severity was associated with Dsg3 antibody levels and a 10-unit increase
      in the Dsg3 ELISA value was associated with a 25% chance of a higher oral
      severity score (CI 17-33%, P < 0.0005). We were unable to demonstrate a
      relationship between Dsg1 antibodies and oral severity, even after adjusting for
      the effect of Dsg3 antibodies. Similarly, there was no relationship between Dsg3
      antibodies and skin severity. CONCLUSIONS: This study suggests that the clinical
      phenotype of pemphigus, in particular the balance of skin and oral disease, is
      determined principally by the quantities of Dsg1 and 3 autoantibodies,
      respectively.

PMID- 11298537
TI  - First experience of topical SDZ ASM 981 in children with atopic dermatitis.
AB  - BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokine release
      under development for the topical treatment of atopic dermatitis. OBJECTIVES:
      This first paediatric study was designed to measure the systemic exposure to SDZ
      ASM 981 in young children with atopic dermatitis treated on extensive skin areas.
      METHODS: Children 1-4 years of age referred to a tertiary care centre for their
      atopic dermatitis were treated twice daily for 3 weeks with 1% SDZ ASM 981 cream.
      SDZ ASM 981 blood concentrations were measured on day 4 and 22 (last day) of
      treatment, and 1 week after the last application, using a radioimmunoassay with a
      limit of quantification of 0.5 ng mL(-1). Efficacy was assessed by the Eczema
      Area Severity Index (EASI). RESULTS: The 10 patients included had 23-69% of their
      body surface area (BSA) affected at baseline. Of the 63 SDZ ASM 981 blood
      concentrations measured, 63% were < 0.5 ng mL(-1); the maximum value observed was
      1.8 ng mL-1. No accumulation was evidenced between days 4 and 22. The first two
      patients experienced a flare of atopic dermatitis that was not controlled by the
      study medication. In the other patients, the EASI improved by 8-89% at 3 weeks of
      treatment. CONCLUSIONS: In these children 1-4 years of age, blood concentrations
      of SDZ ASM 981 during topical treatment with the 1% cream were consistently low
      even in the children with the most extensive areas treated (up to 69% of their
      BSA).

PMID- 11298538
TI  - SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.
AB  - BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro
      inflammatory cytokines from T cells and mast cells in vitro. It is the first
      ascomycin macrolactam derivative under development for the treatment of
      inflammatory skin diseases. OBJECTIVES: This study was designed to determine the
      safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%
      and 1.0% in the treatment of patients with atopic dermatitis and to select the
      concentration to be used in phase III studies. METHODS: This was a double-blind,
      randomized, parallel-group, multicentre dose-finding study. A total of 260
      patients were randomly assigned to treatment with SDZ ASM 981 cream at
      concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the
      internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given
      twice daily for up to 3 weeks. RESULTS: A clear dose-response relationship for
      SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being
      significantly more effective than vehicle (P = 0.041, 0.001 and 0.008,
      respectively) in terms of baseline to end-point changes in the Eczema Area
      Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective
      SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams
      tested in this study. It appears that the efficacy plateau was not reached with
      the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated.
      Burning or a feeling of warmth were the only adverse events reported more
      frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle
      treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse
      events were reported during the study (headache was the most frequent systemic
      event reported by 15 of 252 patients) and none was considered to be related to
      treatment. The local tolerability profile of the 1.0% cream was similar to that
      of the lower concentrations. CONCLUSIONS: 1.0% SDZ ASM 981 cream, which was shown
      to be safe, well tolerated and the most effective concentration in this study,
      was selected as the concentration to be further developed in phase III studies.

PMID- 11298539
TI  - Environmental associations with eczema in early life.
AB  - BACKGROUND: Although atopic eczema (AE) is a common disease, little is known
      about its causes. OBJECTIVES: To investigate the role of dietary and
      environmental factors associated with the development of AE by the age of 2
      years. METHODS: A cohort of children was recruited before birth from a
      consecutive series of newly pregnant mothers presenting for antenatal care at
      three general practices in Ashford, Kent, U.K. Data up to the age of 2 years were
      available for 624 (97%) of the original cohort. AE was defined using components
      of the U.K. diagnostic criteria for AE, maternal report of doctor-diagnosed
      eczema and maternally reported eczema. Exposures of interest were family history
      of allergic disease, dietary and breastfeeding patterns, family size and exposure
      to indoor domestic allergens. RESULTS: The cumulative prevalence of AE using the
      U.K. diagnostic criteria was 14% (95% confidence interval, CI 11-17%). The
      prevalence of maternally reported doctor-diagnosed eczema was much higher (31%,
      95% CI 27-35%) and almost half (45%) the mothers reported that their child had
      ever had eczema (95% CI 41-49%). The relationship between parental atopy,
      parental history of allergic disease and the child's eczema was consistently
      stronger for the mothers than the fathers. There was a marked increase in the
      prevalence of eczema with increasing maternal education and in less crowded
      homes, associations that remained significant after controlling for other
      factors. CONCLUSIONS: The associations with environmental factors are consistent
      with the hypothesis that more crowded houses, increased family size and birth
      order, which may possibly increase early exposure to infections, may offer
      protection from subsequent development of eczema.

PMID- 11298541
TI  - Morbidity in patients with hidradenitis suppurativa.
AB  - BACKGROUND: Although skin diseases are often immediately visible to both patients
      and society, the morbidity they cause is only poorly defined. It has been
      suggested that quality-of-life measures may be a relevant surrogate measure of
      skin disease. Hidradenitis suppurativa (HS) leads to painful eruptions and
      malodorous discharge and is assumed to cause a significant degree of morbidity.
      The resulting impairment of life quality has not previously been quantitatively
      assessed, although such an assessment may form a pertinent measure of disease
      severity in HS. OBJECTIVES: To measure the impairment of life quality in patients
      with HS. METHODS: In total, 160 patients suffering from HS were approached. The
      following data were gathered: quality-of-life data (Dermatology Life Quality
      Index, DLQI questionnaire), basic demographic data, age at onset of the condition
      and the average number of painful lesions per month. RESULTS: One hundred and
      fourteen patients participated in the study. The mean +/- SD age of the patients
      was 40.9 +/- 11.7 years, the mean +/- SD age at onset 21.8 +/- 9.9 years and the
      mean +/- SD duration of the disease 18.8 +/- 11.4 years. Patients had a mean +/-
      SD DLQI score of 8.9 +/- 8.3 points. The highest mean score out of the 10 DLQI
      questions was recorded for question 1, which measures the level of pain,
      soreness, stinging or itching (mean 1.55 points, median 2 points). Patients
      experienced a mean of 5.1 lesions per month. CONCLUSIONS: HS causes a high degree
      of morbidity, with the highest scores obtained for the level of pain caused by
      the disease. The mean DLQI score for HS was higher than for previously studied
      skin diseases, and correlated with disease intensity as expressed by lesions per
      month. This suggests that the DLQI may be a relevant outcome measure in future
      therapeutic trials in HS.

PMID- 11298540
TI  - Increased frequency of HLA-DR6 allele in Italian patients with hepatitis C virus
      associated oral lichen planus.
AB  - BACKGROUND: Recent controlled studies have confirmed that hepatitis C virus (HCV)
      is the main correlate of liver disease in patients with lichen planus (LP),
      mainly in southern Europe and Japan. However, a low prevalence of HCV infection
      has been found in LP patients in England and northern France, and significant
      differences in serum HCV RNA levels or HCV genotypes have not been found between
      LP patients and controls. Thus host rather than viral factors may be prevalent in
      the pathogenesis of HCV-related LP. The HLA-DR allele may influence both the
      outcome of HCV infection and the appearance of symptoms outside the liver.
      OBJECTIVES: To assess whether major histocompatibility complex class II alleles
      play a part in the development of HCV-related LP. METHODS: Intermediate
      resolution DRB typing by hybridization with oligonucleotide probes was performed
      in 44 consecutive Italian oral LP (OLP) patients with HCV infection (anti-HCV and
      HCV RNA positive), in an age, sex and clinically comparable disease control group
      of 60 Italian OLP patients without HCV infection (anti-HCV and HCV RNA negative),
      and in 145 healthy unrelated Italian bone marrow donors without evidence of liver
      disease or history of LP and with negative tests for HCV. RESULTS: Patients with
      exclusive OLP and HCV infection possessed the HLA-DR6 allele more frequently than
      patients with exclusive OLP but without HCV infection (52% vs. 18%, respectively;
      Pc (Pcorrected) = 0.028, relative risk = 4.93). We did not find any relationship
      between mucocutaneous LP, HCV infection and HLA-DR alleles. CONCLUSIONS: HCV
      related OLP therefore appears to be a distinctive subset particularly associated
      with the HLA class II allele HLA-DR6. This could partially explain the peculiar
      geographical heterogeneity of the association between HCV and LP.

PMID- 11298542
TI  - Potassium titanyl phosphate laser treatment of resistant port-wine stains.
AB  - BACKGROUND: The pulsed dye laser (PDL; 585 nm, 450 micros pulse) has been
      established as the treatment of choice for port-wine stains (PWS), but only few
      patients have total clearance. A modulated potassium titanyl phosphate (KTP)
      laser (532 nm) has been developed that allows the adjustment of energy fluences
      within the 5-50 J cm-2 range with laser pulse widths between 1 and 50 ms at pulse
      rates from 1 to 20 pulses s(-1). OBJECTIVES: To determine the efficacy and side
      effect rate of the KTP laser in treating PDL-resistant PWS. METHODS: Thirty
      patients were recruited. The site and colour of the PWS were recorded and
      assessed with erythemameter readings, videomicroscopy and photography both before
      and after treatment. All patients had test areas treated on their first visit and
      were then reviewed at 2-monthly intervals. Repeat treatments were given if no
      adverse effects had occurred and if the treated areas had shown between 25 and
      100% lightening. RESULTS: Thirty patients were assessed, age range 11-63 years
      (mean 35.4) with 19 females. The PWS affected the face in 21 (70%) patients, leg
      in five (17%) and other sites in four (13%). Patients had one to four tests or
      treatments (mean 2.2) with the KTP laser. Overall, 16 (53%) patients showed > 25%
      response and five (17%) showed > 50% response to treatments with the KTP laser.
      Best responses were found with fluences ranging from 18 to 24 J cm(-2) with pulse
      width 9-14 ms. No correlation was found with the colour of the PWS or the number
      of previous treatments with PDL. Patients preferred the KTP laser treatments
      compared with the PDL (visual analogue score mean 9.8; n = 5) with less
      discomfort during treatments and minimal purpura post-treatment. Six patients
      (20%) developed side-effects: scarring (n = 2, 7%), hyperpigmentation (n = 3,
      10%) and prolonged healing phase of over 4 weeks (n = 1, 3%). CONCLUSIONS: We
      have shown that the KTP laser can further lighten PDL-resistant PWS and that it
      is a useful addition to the laser treatment of PWS. Further studies need to
      assess the efficacy and side-effects of the KTP laser in previously untreated
      PWS.

PMID- 11298543
TI  - Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital
      herpes infections: a parallel-groups, randomized, double-blind clinical trial.
AB  - BACKGROUND: Twice-daily therapy with famciclovir (FCV) was shown to be effective
      for episodic therapy for recurrent genital herpes in a large placebo-controlled
      trial. However, no study has been published to date comparing FCV and aciclovir
      (ACV). OBJECTIVES: We have evaluated the effectiveness of FCV vs. ACV in the
      treatment of recurrent genital herpes infection. METHODS: A multicentre, double
      blind, double-placebo, randomized, parallel-design study, assessed for
      equivalence, was conducted. As the analysis was based on confidence intervals, a
      difference of lesion healing time between ACV and FCV (Delta) of 1.05 days with a
      standard deviation of 2.30 days was chosen. Two hundred and four outpatients were
      included. Patients self-initiated oral therapy with 125 mg of FCV twice daily or
      ACV 200 mg five times daily for 5 days. The principal end-point of the study was
      the complete healing of lesions. Duration of the complete resolution of all
      symptoms, and safety were also considered. RESULTS: The mean healing time was 5.1
      days and 5.4 days for FCV and ACV, respectively, with a crude value of Delta =
      0.25 days (CI 95%: -0.32; 0.82) in the intent-to-treat population. Therefore, the
      confidence interval for the difference between the two treatments lies entirely
      within the equivalence range (-1.05-1.05). The value of Delta in the per-protocol
      population [0.35 day (CI 95%: -0.24; 0.93)] was comparable between the two
      groups. No differences were detected in the proportion of patients having
      complete healing at the different days of evaluation as well as in the duration
      until the complete resolution of all the symptoms. The frequency, nature and
      severity of adverse events did not differ among the two treatment groups.
      CONCLUSIONS: Twice-daily FCV was as effective and safe in the treatment of
      recurrent genital herpes simplex virus infection as five times daily ACV.

PMID- 11298544
TI  - Predicting factors of malignancy in dermatomyositis and polymyositis: a case
      control study.
AB  - BACKGROUND: An association between dermatomyositis (DM)/polymyositis (PM) and
      malignancies has been widely reported in the literature. The validity of
      extensive evaluation for malignancies in those patients has also been questioned
      for decades. Only limited papers regarding the signs of malignancy and the
      prognostic factors in DM/PM have been reported. OBJECTIVES: To define the
      potential risk factors of concomitant neoplastic diseases in patients diagnosed
      as having DM/PM. METHODS: From 1 April 1983 to 30 June 1999, 147 patients were
      diagnosed as having probable or definite DM/PM at the Veterans General Hospital,
      Taichung, Taiwan. We excluded four patients who had preceding neoplastic diseases
      diagnosed before DM/PM, then retrospectively reviewed the data of the remaining
      143 patients and subgrouped the cases as four main types: primary idiopathic DM,
      primary idiopathic PM, juvenile DM/PM and amyopathic DM (ADM). We next performed
      univariate analysis using logistic regression to evaluate the possible predictive
      factors for malignancies, such as mean age at onset, gender, manifestations at
      onset, association with other connective tissue diseases, initial skin
      presentations, complications and laboratory data. Then we chose the significant
      factors for multivariate analysis by logistic regression, to determine the
      independent risk factors of malignancies in DM/PM patients. RESULTS: Among the
      143 patients, DM was the most common type (64%), followed by ADM (14%), juvenile
      DM/PM (13%) and PM (10%). The mean age at onset overall was 42.4 years. Other
      connective tissue diseases were present in 22% of all patients, especially PM
      (50%) and juvenile DM/PM patients (28%). Internal malignancies were present in
      13% of patients, and most were associated with DM. Nasopharyngeal carcinomas
      (NPCs) were the most common tumours. Patients with primary idiopathic DM, with an
      older age at onset, higher serum creatine phosphokinase levels and male gender,
      had more chance of developing concomitant malignancies. Those associated with
      complications, especially interstitial lung diseases, had a lower risk of
      associated neoplasia. In multivariate analysis, an older age at onset (odds ratio
      9.10) and male gender (odds ratio 4.06) were associated with greater risk of
      developing malignancies. CONCLUSIONS: The two independent predictive factors for
      malignancy (P < 0.05) in patients with DM/PM were an older age at onset (> 45
      years) and male gender. The primary idiopathic DM group was shown to have higher
      risk of developing internal malignancies, especially NPC. However, this was not
      identified as an independent predictive factor for concomitant neoplastic
      diseases in multivariate analysis. In addition, patients who had the complication
      of interstitial lung disease had a significantly lower frequency of malignancies
      (P < 0.001).

PMID- 11298545
TI  - Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase
      III clinical trial.
AB  - BACKGROUND: A previously reported randomized clinical trial showed treatment of
      Bowen's disease using photodynamic therapy (PDT) with topically applied delta
      aminolaevulinic acid (ALA) to be at least as effective as cryosurgery and to be
      associated with fewer adverse effects. OBJECTIVES: To compare ALA-PDT and
      cryotherapy in the treatment of histopathologically verified basal cell
      carcinomas (BCCs) in a non-blinded, prospective phase III clinical trial.
      METHODS: One lesion from each of 88 patients was included. The BCCs were divided
      into superficial and nodular lesions. The follow-up period was restricted to 1
      year with close follow-up for the first 3 months. Efficacy was assessed as the
      recurrence rate 12 months after the first treatment session, verified by
      histopathology. Tolerability was evaluated as the time of healing, pain and
      discomfort during and after the treatment, and final cosmetic outcome. RESULTS:
      Histopathologically verified recurrence rates in the two groups were
      statistically comparable and were 25% (11 of 44) for ALA-PDT and 15% (six of 39)
      for cryosurgery. However, clinical recurrence rates were only 5% (two of 44) for
      PDT and 13% (five of 39) for cryosurgery. Additional treatments, usually one, had
      to be performed in 30% of the lesions in the PDT group. The healing time was
      considerably shorter and the cosmetic outcome significantly better with PDT. Pain
      and discomfort during the treatment session and in the following week were low,
      and were equivalent with the two treatment modalities. CONCLUSIONS: In terms of
      efficacy, ALA-PDT is comparable with cryosurgery as a treatment modality for
      BCCs. Retreatments are more often required with PDT than with cryosurgery. This
      can easily be performed due to the shorter healing time, less scarring and better
      cosmetic outcome that follows ALA-PDT.

PMID- 11298546
TI  - Analysis of p53 and BAX mutations, loss of heterozygosity, p53 and BCL2
      expression and apoptosis in basal cell carcinoma in Korean patients.
AB  - BACKGROUND: Apart from some Japanese studies, there are few data on the gene
      mutations involved in the development of basal cell carcinomas (BCC) in Koreans
      or other Asians. Objective To gain insight into the molecular pathogenesis of BCC
      in Koreans. METHODS: A collection of 33 cases of BCC were screened for mutations
      of p53 and BAX genes, p53 and BCL2 expression, loss of heterozygosity (LOH) and
      apoptosis. RESULTS: Mutations of p53, found in 9% (three of 33) of the cases,
      were all mis-sense mutations (G-->C transversions) at codon 246 on exon 7. In 6%
      (two of 33), BAX gene showed frameshift mutations resulting from deletions in the
      poly(G) tract. LOH on chromosome 9q was seen in 58% (14 of 24), and p53 mutations
      developed only among the 9q LOH+ cases; LOH on chromosome 18q, where BCL2 gene is
      located, was found in 13% (four of 30). Immunohistochemical expression of p53 was
      seen in 27% (nine of 33), and its expression did not coincide with p53 mutations.
      BCL2 expression was seen in 39% (13 of 33). Apoptosis was revealed in 21%. In
      BCC, 9q LOH and p53 mutations seem to be closely related; the immunoreactivity of
      p53 and its mutations were not directly related; and p53 and BCL2 expression were
      negatively correlated. Frameshift mutations of the BAX gene in BCC are documented
      for the first time. CONCLUSIONS: Various molecular mechanisms operate with
      redundant complexity in the pathogenesis of BCC. The LOH on chromosome 9q is the
      most frequent genetic alteration, as in other races; however, p53 mutations are
      much less frequent in Koreans than in Caucasians and suggest aetiologies other
      than ultraviolet radiation.

PMID- 11298547
TI  - Cytokine gene polymorphisms in psoriasis.
AB  - BACKGROUND: Cytokine production is under genetic control, and certain allelic
      variants of cytokine genes are associated with higher or lower cytokine
      production in vitro and in vivo. Psoriasis is associated with an overexpression
      in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon
      (IFN) -gamma and tumour necrosis factor (TNF) alpha and relative underexpression
      of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated
      the hypothesis that allelic variants of genes for a high production of Th1
      cytokines or TNF-alpha, or conversely low production of Th2 cytokines might
      represent a risk factor for developing psoriasis. METHODS: Genotyping for IFN
      gamma, IL-10, IL-4 and TNF-alpha was undertaken for 84 patients with psoriasis
      and compared with control data on file. RESULTS: Genotype frequencies showed no
      differences between patients and controls for IFN-gamma, TNF-alpha or IL-4. For
      IL-10, patients with late onset psoriasis (over 40 years) were more likely to be
      heterozygous at position - 1082 (P = 0.02), corresponding to intermediate
      production of IL-10 in vitro and in vivo. CONCLUSIONS: Psoriasis is not
      determined by a genotype consistent with high production of Th1 cytokines or low
      production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic
      plaques is most likely a consequence of local factors.

PMID- 11298548
TI  - Evaluation of the efficacy and tolerability of oral terbinafine (Daskil) in
      patients with seborrhoeic dermatitis. A multicentre, randomized, investigator
      blinded, placebo-controlled trial.
AB  - BACKGROUND: Previous uncontrolled trials have suggested that oral terbinafine, an
      antimycotic allylamine compound, could be useful in the treatment of seborrhoeic
      dermatitis. OBJECTIVES: To investigate in a placebo-controlled trial the clinical
      efficacy of oral terbinafine (Daskil(R), Mipharm, Milan, Italy) in patients with
      moderate to severe seborrhoeic dermatitis. METHODS: Sixty outpatients (mean +/-
      SD age 37 +/- 11 years; 32 men and 28 women) with moderate to severe seborrhoeic
      dermatitis were enrolled in a multicentre, randomized, placebo-controlled,
      investigator-blinded, parallel-group, 12-week study. After a 2-week wash-out
      period, enrolled patients were randomized to treatment with oral terbinafine 250
      mg daily (n = 30) or placebo (moisturizing ointment) (n = 30) applied twice daily
      for 4 weeks (weeks 0-4). Patients were followed up for an additional 8 weeks
      after completion of treatment and were clinically evaluated at weeks 0, 2, 4 and
      12 by an investigator unaware of the patient's type of treatment. The primary end
      point of the study was clinical evaluation of erythema, scaling and itching, each
      scored on a 0-3 scale. A global clinical score, representing the sum of each
      evaluated symptom, was also calculated. RESULTS: Demographic and clinical data
      were equally balanced between the placebo and terbinafine groups. All enrolled
      patients concluded the study. At baseline, the mean +/- SD global clinical score
      was 7.4 +/- 1.3 in the placebo group and 7.7 +/- 1.0 in the terbinafine-treated
      group. At weeks 4 and 12 the mean +/- SD global clinical score in the placebo
      group was 5.9 +/- 1.7 and 6.3 +/- 1.2, respectively, which was not significantly
      different from baseline. As compared with baseline values and the placebo group,
      terbinafine treatment significantly (P < 0.0001, Tukey-Kramer test) reduced the
      mean +/- SD global clinical score (to 1.0 +/- 1.1 at week 4, and 1.2 +/- 1.4 at
      week 12), as well as the individual erythema, scaling and itching scores. No
      serious adverse events were recorded during the study in either group.
      CONCLUSIONS: This is the first controlled trial that has shown oral terbinafine
      to be effective in the treatment of moderate to severe seborrhoeic dermatitis.
      Clinical improvement following 4 weeks treatment with terbinafine was maintained
      8 weeks after completing treatment.

PMID- 11298549
TI  - Urocanic acid isomers in patients with non-melanoma skin cancer.
AB  - BACKGROUND: Cis-urocanic acid (cis-UCA), formed from the naturally occurring
      trans-isomer in the epidermis on ultraviolet (UV) radiation, initiates some of
      the changes leading to UV-induced immunosuppression, but its role in cutaneous
      carcinogenesis has not been fully investigated. OBJECTIVES: To measure the
      concentration of UCA isomers in the photoexposed and non-photoexposed skin of
      patients with multiple non-melanoma skin cancer (NMSC), enrolled in different
      periods of the year, in comparison with control subjects. PATIENTS/METHODS: UCA
      isomers were determined by high-performance liquid chromatography analysis in
      samples from the outer arm (photoexposed site) and buttock (non-photoexposed
      site) obtained from 20 patients and 19 controls during the winter period (October
      to April), and from five patients and 11 controls during the summer period (June
      to September). RESULTS: In the winter months, no difference was found between
      patients and controls in the concentration of UCA or the percentage of cis-UCA in
      either site. In the summer months, the percentage of cis-UCA in the buttock of
      patients and controls was similar but it was significantly higher in the arm of
      the controls (42%) than in the patients (17%). CONCLUSIONS: We conclude that
      different behaviour regarding sun exposure is the most likely explanation for
      these results, and that the concentration of UCA and its isomers does not reflect
      a tendency for individuals to develop NMSC.

PMID- 11298550
TI  - Immunoglobulin heavy chain variable region family expression in primary cutaneous
      follicle centre cell lymphomas.
AB  - BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCL) are the
      most common type of primary cutaneous B-cell lymphomas. Patients with this
      disorder develop one or a few clinically indolent tumour nodules, plaques, or
      papules confined to a circumscribed area. Only limited data have so far been
      published on the use of immunoglobulin heavy chain variable region (VH) families
      by these tumours. OBJECTIVES: Because the definition of the repertoire of VH
      genes could have significant biological and diagnostic implications, we evaluated
      a group of patients with PCFCCL for VH family use. METHODS: DNA obtained from 15
      cases of PCFCCL was amplified by polymerase chain reaction (PCR) using a panel of
      VH family-specific amplimers. RESULTS: The pattern of VH family usage was similar
      to that reported in both normal peripheral blood B cells and the most common low
      grade non-Hodgkin's lymphomas, where VH region utilization is essentially random
      with frequent usage of the VH3 family. CONCLUSIONS: These findings support the
      hypothesis that PCFCCL may derive from the mature peripheral lymphoid
      compartment. Our results may also have implications for the routine analysis of B
      lymphoid clonality in PCFCCL.

PMID- 11298551
TI  - Homozygous variegate porphyria: a compound heterozygote with novel mutations in
      the protoporphyrinogen oxidase gene.
AB  - Homozygous variegate porphyria results from mutations in both alleles of the
      protoporphyrinogen oxidase (PPOX) gene. Our patient, a 36-year-old woman, has
      severe cutaneous manifestations. Her clinical and biochemical features are
      similar to the few other reported cases, including onset before 18 months of age,
      photosensitivity, absence of acute porphyric attacks, and elevated erythrocyte
      protoporphyrin. Mutation analysis of the PPOX gene revealed an in-frame 12 bp
      insert (c. 657-658 ins AAGGCCAGCGCC) encoding lysine-alanine-serine-alanine
      (KASA), and a G to A transition at the splice donor site of exon 11 (IVS 11-1 G-
      >A). Neither of these mutations has been reported previously. Our patient's
      mother has the splice site mutation and has had acute porphyric episodes. A
      maternal first cousin has the same mutation but no clinical manifestations. The
      medical and family history of our patient's father is uncertain.

PMID- 11298552
TI  - Linear IgA bullous dermatosis in a patient with renal cell carcinoma.
AB  - Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal bullous
      disease with heterogeneous clinical manifestations, characterized by linear
      deposition of IgA along the epidermal basement membrane zone. We report a patient
      with a metastasized renal cell carcinoma who developed an extensive blistering
      eruption. The lesions showed immunopathological findings characteristic of LABD.
      The patient showed a fair response to prednisolone and dapsone. Treatment to
      control the LABD was no longer required when interferon-alfa was started as
      palliative therapy for the metastasized renal cell carcinoma. The association of
      LABD and malignancies has been documented before and is not due to mere chance
      alone.

PMID- 11298553
TI  - Late-onset hydroa vacciniforme: two case reports.
AB  - Hydroa vacciniforme (HV) is a rare blistering photodermatosis that heals with
      vacciniform scarring, with onset usually in childhood and spontaneous resolution
      by early adulthood. We report two cases of HV seen at the National Skin Centre,
      Singapore, both with a late onset at 20 years of age, during compulsory military
      service, and one with a less typical non-vesicular presentation, that initially
      caused some diagnostic difficulties.

PMID- 11298554
TI  - Angioimmunoblastic lymphadenopathy-type peripheral T-cell lymphoma with cutaneous
      infiltration: report of a case and its gene expression profile.
AB  - Angioimmunoblastic T-cell lymphoma is a type of peripheral T-cell lymphoma that
      is clinically characterized by high fever and generalized lymphadenopathy with or
      without cutaneous involvement. A 55-year-old Japanese man presented with red
      papular lesions on the trunk and limbs, oedema, and generalized lymphadenopathy.
      Histological findings in the lymph nodes showed destructive germinal centres,
      proliferation of arborizing postcapillary venules, and atypical medium-sized
      lymphocytes. The cutaneous lesions also contained atypical lymphocytes.
      Immunohistochemical studies indicated that the neoplastic cells were mature CD4+
      T lymphocytes. Southern blot analysis detected a clonal expansion of T-cell
      receptor beta. Based on these findings, a diagnosis of angioimmunoblastic T-cell
      lymphoma with cutaneous infiltration was made. Despite systemic chemotherapy, the
      disease exhibited a high level of activity and continued on a fatal course. An
      analysis of gene expression profiling using complementary DNA microarrays
      revealed significant expression of some chemokines and cytokines, e.g. secondary
      lymphoid tissue chemokine, macrophage inflammatory protein (MIP)-1beta, MIP
      3alpha, MIP-3beta, B-lymphocyte chemokine, interleukin-16 and tumour necrosis
      factor-beta, and an apoptosis-inhibitory protein (FLICE inhibitory protein) in
      the affected lymph nodes. Profiling of gene expression patterns for a variety of
      genes in additional cases may be helpful in determining which factors predict the
      biological and clinical behaviour of angioimmunoblastic T-cell lymphoma or other
      aggressive malignant lymphomas.

PMID- 11298555
TI  - Kikuchi's disease and the skin: case report and review of the literature.
AB  - We report scattered indurated erythematous lesions that presented in an 18-year
      old Japanese man with Kikuchi's disease (KD; histiocytic necrotizing
      lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant
      nuclear debris without the presence of neutrophils, which is characteristic of
      KD. The specific dermatological and pathological details of KD have been yet to
      be fully described. In order to assess the typical skin features of KD better, we
      have reviewed all the previously well-documented reports of such lesions. As the
      clinical and histopathological cutaneous findings in KD are so heterogeneous, it
      is important that scattered indurated erythematous lesions should be included as
      one of the possible cutaneous manifestations of this disease.

PMID- 11298556
TI  - The Buschke-Ollendorff syndrome presenting as familial elastic tissue naevi.
AB  - We present a family with Buschke-Ollendorff syndrome presenting as elastic tissue
      naevi without evidence of osteopoikilosis. We discuss the variable expression of
      this syndrome in other families previously reported in the literature, the
      association of various connective tissue abnormalities and their correlation with
      the pathogenesis of this interesting condition.

PMID- 11298557
TI  - An extremely severe case of cutaneous calcinosis with juvenile dermatomyositis,
      and successful treatment with diltiazem.
AB  - A case of cutaneous calcinosis associated with juvenile dermatomyositis is
      described. The patient was a 3-year-old girl who had been diagnosed as having
      dermatomyositis at age 1 year. She was treated with prednisolone, but developed
      multiple calcified nodules in the subcutaneous tissues and intermuscular fascia.
      These nodules gradually increased in size despite continual therapy with steroids
      and aluminium hydroxide. Treatment with diltiazem completely suppressed the
      development of calcinosis.

PMID- 11298558
TI  - Tinea capitis in two elderly women: transmission at the hairdresser.
AB  - Tinea capitis is rare in the elderly. We report cases of two elderly women who
      presented to our dermatology clinic within 8 weeks of each other, with scalp
      scaling and alopecia. In both cases, Microsporum canis grew on fungal culture of
      their hair, and required prolonged treatment with terbinafine. Neither of them
      gave a history of contact with young children or any animals. Both were fairly
      fit and not systemically immunocompromised. However, both had been regularly
      visiting the same hairdresser, during the presumed period of infectivity, making
      this the most likely source of infection.

PMID- 11298559
TI  - Treatment of severe erythrodermic acute graft-versus-host disease with
      photochemotherapy.

PMID- 11298560
TI  - Differential expression of Fas in tumour-stage mycosis fungoides (MF) and MF-like
      cutaneous T-cell pseudolymphoma.

PMID- 11298561
TI  - Primary cutaneous pleomorphic small/medium-sized T-cell lymphoma in a young man.

PMID- 11298562
TI  - Panniculitis heralding blastic transformation of myelofibrosis.

PMID- 11298563
TI  - Granulomatous disease associated with HLA class I deficiency.

PMID- 11298564
TI  - Management of ulcerated necrobiosis lipoidica: an innovative approach.

PMID- 11298565
TI  - Mononuclear variant of juvenile xanthogranuloma in the oral cavity of an adult
      patient.

PMID- 11298566
TI  - Congenital malalignment of the left index fingernail.

PMID- 11298567
TI  - Effect of house dust mite avoidance measures in children with atopic dermatitis.

PMID- 11298569
TI  - Dermatology and the world wide web.

PMID- 11298570
TI  - Nodular lichen simplex of the scrotum treated by surgical excision.

PMID- 11298571
TI  - Synergistic toxicity of delta-aminolaevulinic acid-induced protoporphyrin IX used
      for photodiagnosis and hypericum extract, a herbal antidepressant.

PMID- 11298572
TI  - Everybody's free (to wear sunscreen): the power of pop.

PMID- 11298573
TI  - Nasolabial follicular sebaceous casts: a novel complication of isotretinoin
      therapy.

PMID- 11298575
TI  - Isotretinoin use and reports of sustained dreaming.

PMID- 11298576
TI  - Amlodipine-associated lichen planus.

PMID- 11298577
TI  - Bilateral retinal haemorrhages: an unusual presentation of pernicious anaemia.

PMID- 11298578
TI  - Which children with fever and neutropenia can be safely treated as outpatients?

PMID- 11298579
TI  - The embryonic origins of human haematopoiesis.

PMID- 11298580
TI  - Kasabach-Merritt syndrome: pathogenesis and management.

PMID- 11298581
TI  - Acquired immunodeficiency syndrome-related systemic non-Hodgkin's lymphoma.

PMID- 11298582
TI  - Dendritic cells and immunotherapy for malignant disease.

PMID- 11298583
TI  - The spherocytic haemolytic anaemias.

PMID- 11298584
TI  - Acute myeloid leukaemia in human immunodeficiency virus-infected adults:
      epidemiology, treatment feasibility and outcome.
AB  - The epidemiology and clinical outcome of acute myeloid leukaemia in human
      immunodeficiency virus (HIV)-infected adults is poorly documented. We
      retrospectively surveyed all French haematology centres for adult acute myeloid
      leukaemia (AML) cases diagnosed between January 1990 and July 1996 who were found
      to be HIV-seropositive before or at the time of AML diagnosis. Medical charts
      were reviewed to determine the stage of HIV infection, the characteristics of AML
      and the response of AML to chemotherapy. Sixteen cases of AML (13 men, three
      women) were reported by 12 haematology units. Based on assumptions on the size,
      age and sex distribution of the HIV-infected population in France, the estimated
      risk of AML in 1990 to 1996 among HIV-infected adults was twice that of the
      general population (standardized incidence ratio = 2.05; 95% confidence interval,
      1.17-3.34). Two other cases occurring before 1990 were spontaneously notified to
      the authors and were included in the clinical analysis. At AML diagnosis, the
      median CD4+ cell count was 275 x 106/l and nine patients had acquired immune
      deficiency syndrome (AIDS). Fifteen patients were scheduled for remission
      induction therapy of AML. No deaths were related to AML treatment. Complete
      remission was obtained in 11 out of 15 patients. Three patients were long-term
      survivors: two remain alive in complete remission at 8 years and 9 years,
      respectively, and the third died of AIDS at 8 years. A CD4+ cell count above 200
      x 106/l at AML diagnosis was predictive of longer survival (log-rank test: P =
      0.004). Like many other malignancies, the incidence of AML appears to be
      increased in HIV-infected patients. Our results show a twofold higher incidence,
      although this needs to be confirmed in a specifically designed prospective
      epidemiological study. Such patients, especially those with CD4+ cell counts
      above 200 x 106/l at AML diagnosis, should receive remission-induction therapy,
      which can confer long-term survival.

PMID- 11298585
TI  - Influence of highly active anti-retroviral therapy on response to treatment and
      survival in patients with acquired immunodeficiency syndrome-related non
      Hodgkin's lymphoma treated with cyclophosphamide, hydroxydoxorubicin, vincristine
      and prednisone.
AB  - Combined highly active anti-retroviral therapy (HAART) with protease and reverse
      transcriptase inhibitors has modified the natural history of opportunistic
      infections and neoplasms in human immunodeficiency virus (HIV)-infected patients.
      We analysed the influence of HAART on the response to treatment and survival in a
      series of 58 patients with acquired immune deficiency syndrome (AIDS)-related non
      Hodgkin's lymphoma (NHL) treated with CHOP (cyclophosphamide, hydroxydoxorubicin,
      vincristine and prednisone). Two groups of patients were included: (i) forty-one
      patients diagnosed with NHL between 1988 and 1996 who were not treated with
      HAART; (ii) seventeen patients diagnosed since 1996, who were receiving or
      commenced HAART when NHL was diagnosed. The response rate to CHOP was higher in
      group 2 (13 out of 17 cases; 75%) than in group 1 (14 out of 41 cases; 34%) (P =
      0.003). The 2-year probability of event-free survival (EFS) [95% confidence
      interval (CI)] for group 1 was 0.5 (0.24-0.74), whereas for group 2 it was 0.85
      (0.61-0.90) (P = 0.024). The lymphoma-free survival (LFS) was also significantly
      different for both groups (2-year LFS probability 0.53 vs. 1.0, P = 0.04). The
      median (95% CI) overall survival (OS) for group 1 was 7 months (range, 3-10.8
      months), whereas it was not reached in group 2 (P = 0.0015). In the multivariate
      analysis for remission attainment, the only variables with a higher probability
      to achieve complete remission (CR) were HAART (P = 0.01) and International
      Prognostic Index score 1 (P = 0.02). The only statistically significant variable
      in the multivariate analysis for EFS was HAART (P = 0.049) and the variables with
      prognostic value for OS in the multivariate analysis were B symptoms (P = 0.01)
      and HAART (P = 0.003). Patients with AIDS-related NHL treated with CHOP and HAART
      had a higher CR rate than those treated only with CHOP. In this study, HAART was
      an independent prognostic factor for CR, OS and EFS in patients with AIDS-related
      NHL.

PMID- 11298587
TI  - Occupational and environmental risk factors of the myelodysplastic syndromes in
      the North of France.
AB  - Aetiological factors of the myelodysplastic syndromes (MDS) are largely unknown,
      with the exception of alkylating agents, ionizing radiation and benzene. Some
      other risk factors have been suggested by the few epidemiological studies
      reported (solvents, ammonia, exhaust gases, metals, pesticides, alcohol). We
      performed a case-control study to assess the relationship between occupational or
      environmental factors and MDS. Two hundred and four patients with newly diagnosed
      MDS, and 204 sex- and age-matched controls were included. Medical history,
      demographic data, lifetime exposure and hobbies were obtained. Qualitative and
      quantitative exposure to chemical and physical hazards were evaluated with the
      patients and reviewed by a group of experts in occupational exposure. The median
      age was 70 years and 62% of the patients were men. In univariate analyses, we
      found relationships between MDS and smoking habits, gardening, occupations such
      as health professionals, technical and sale representatives, machine operators,
      agricultural workers, textile workers, qualitative occupational exposures
      (exposed/non-exposed) to oil, solvents, ammonia, pesticides, fertilizers, cereal
      dusts, contact with poultry or livestock and infective risk, and lifetime
      cumulative exposure to solvents, oil, textile dust and infective risk. The main
      risk factors of MDS determined by multivariate analyses (conditional logistic
      regression) were, being an agricultural worker [odds ratio (OR) = 3.66; 95%
      confidence interval (CI) 1.9-7.0], textile operator (OR = 3.66; 95% CI 1.9-7.9),
      health professional (OR = 10.0; 95% CI 2.1-48.7), commercial and technical sale
      representative (OR = 4.45; 95% CI 1.4-14.6), machine operator (OR = 2.69; 95% CI
      1.2-6.0), living next to an industrial plant (OR = 2.45; 95% CI 1.5-4.1), smoking
      (OR = 1.74; 95% CI 1.1-2.7) and lifetime cumulative exposure to oil (OR = 1.1;
      95% CI 1.0-1.2). Further studies should be performed to assess specific exposures
      more precisely and it would be of interest to develop a map of haematological
      malignancies according to industrial background.

PMID- 11298586
TI  - Quantitative monitoring of the PRAME gene for the detection of minimal residual
      disease in leukaemia.
AB  - PRAME (Preferentially expressed antigen of melanoma) has been previously
      identified as a melanoma antigen recognized by cytotoxic T cells (CTLs) and found
      to be expressed in a variety of cancer cells including leukaemic cells. We have
      screened 98 Japanese patients with leukaemia and lymphoma for expression of the
      PRAME gene using semiquantitative reverse transcription polymerase chain reaction
      (RT-PCR). Forty-one patients (42%) showed high levels of PRAME expression. Eight
      of these patients were then monitored using real-time PCR for a period of 10-37
      months. Significant reductions in the PRAME expression were observed in all
      patients after chemotherapy. An increased expression was detected in the two
      patients who relapsed, one of which was before cytological diagnosis. These
      changes were correlated with those of other known genetic markers, such as the
      bcr-abl gene. Therefore, quantitative monitoring of the PRAME gene using real
      time PCR method may be useful for detecting minimal residual disease and to
      predict subsequent relapse, especially in patients without known genetic markers.
      In addition, a PRAME-positive leukaemia cell line and fresh leukaemic cells were
      found to be susceptible to lysis by PRAME-specific CTLs established from a
      patient with melanoma, suggesting that the PRAME peptide can also be a target
      leukaemia antigen for T cells.

PMID- 11298588
TI  - Somatostatin receptor scintigraphy useful in stage I-II Hodgkin's disease: more
      extended disease identified.
AB  - Somatostatin receptor (SS-R) scintigraphy successfully shows primary cancers and
      metastases in patients with a variety of SS-R-positive tumours. In vitro studies
      have shown that SS-Rs are present in lymph nodes from patients with Hodgkin's
      disease (HD). We performed a prospective study in 126 newly diagnosed patients
      with HD and compared the results of SS-R scintigraphy with conventional staging
      procedures, i.e. physical examination, computerized tomography (CT) scanning and
      other imaging techniques. We report positive scintigraphy in all patients. The
      lesion-related sensitivity was 94% and varied from 98% for supradiaphragmatic
      lesions to 67% for infradiaphragmatic lesions. In comparison with CT scanning and
      ultrasonography, SS-R scintigraphy provided superior results for the detection of
      Hodgkin's localizations above the diaphragm. In the intra-abdominal region, the
      CT scan was more sensitive than the SS-R scan. A false-positive scan was rarely
      seen. In stages I and II supradiaphragmatic HD patients, SS-R scintigraphy
      detected more advanced disease in 18% (15 out of 83) of patients, resulting in an
      upstaging to stage III or IV, thus directly influencing patient management. Our
      data would support the validity of SS-R scanning as a powerful imaging technique
      for the staging of patients with HD.

PMID- 11298589
TI  - Prognostic significance of tumour-infiltrating T lymphocytes and T-cell subsets
      in de novo diffuse large B-cell lymphoma: a multiparameter flow cytometry study.
AB  - Tumour-infiltrating T lymphocytes (TIL-T) have been implicated in playing a role
      in controlling tumour growth. We evaluated TIL-T in 55 cases of de novo diffuse
      large B-cell lymphoma (DLBCL) using three- or four-colour flow cytometric
      immunophenotyping (FCI). The percentage of TIL-T varied from 3% to 72% of total
      viable cellular events (mean 32 +/- 20%). The CD4:CD8 ratio varied from 0.17 to
      13 (mean 2.3 +/- 2.2). Cases with >/= 20% T cells and those with CD4:CD8 ratios >
      or = 2.0 showed a significantly better overall survival (P = 0.017 and P = 0.034
      respectively). These findings were independent of clinical stage at diagnosis.
      The T-cell percentage and CD4:CD8 ratio were moderately correlated (Spearman
      correlation coefficient = 0.47, P = 0.001) and multivariate analysis revealed
      that the association of the two factors with prognosis was mutually dependent.
      The T cells in 23 cases were studied for CD45RO. The mean percentage of total T
      cells expressing CD45RO was 86 +/- 10%. There was a trend towards better survival
      for those patients with a higher percentage of CD45RO+ T cells (P = 0.06). These
      results suggest that TIL-T, particularly CD4+ T cells, may play a role in the
      control of DLBCL, and measurement of T-cell percentage and T-cell subsets using
      FCI may be useful in predicting the clinical behaviour of DLBCL.

PMID- 11298590
TI  - The Polycomb group protein EZH2 is upregulated in proliferating, cultured human
      mantle cell lymphoma.
AB  - Polycomb group (PcG) proteins are involved in the stable transmittance of the
      repressive state of their gene targets throughout the cell cycle. Mis-expression
      of PcG proteins can lead to proliferative defects and tumorigenesis. There are
      two separate multimeric PcG protein complexes: an EED-EZH2-containing complex and
      a BMI1-RING1-containing complex. In the normal human follicle mantle, both PcG
      complexes have mutually exclusive expression patterns. BMI1-RING1 is expressed,
      but EZH2-EED is not. Here, we studied the expression of both complexes in six
      cases of mantle cell lymphoma (MCL), which is derived from the follicle mantle.
      MCL cells can be cultured in vitro and stimulated to proliferation. We found that
      resting MCL cells expressed BMI1-RING1, but not EZH2-EED, like normal mantle
      cells. Proliferating MCL cells, however, showed strongly enhanced expression of
      EZH2. Also, BMI1 and RING1 continued to be expressed in proliferating MCL. This
      is the first demonstration that EZH2 expression can be upregulated in fresh
      lymphoma cells. To test whether the enhanced EZH2 expression was causal for the
      increased proliferation in MCL, we overexpressed EZH2 in two different cell
      lines. In the B cell-derived Ramos cell line, EZH2 overexpression caused an
      increase in the proliferation rate. This suggests a possible causal effect
      between EZH2 upregulation and increased proliferation in haematopoietic cells.

PMID- 11298591
TI  - Analysis of the expression of critical activation/interaction markers on
      peripheral blood T cells in B-cell chronic lymphocytic leukaemia: evidence of
      immune dysregulation.
AB  - B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by an accumulation
      of clonal malignant B cells. The intrinsic characteristics that permit this
      accumulation have been extensively studied and described. However, it is possible
      that proliferation and survival of this malignant clone is facilitated by a
      disruption in the interaction between B and T cells that normally regulate the
      immune system. In this study, using flow cytometry and cell culture techniques,
      marked abnormalities of the expression of certain key activation and interaction
      molecules on the peripheral blood T cells of patients with B-CLL were
      demonstrated. In particular, on comparison with normal controls, there was a
      marked reduction in the number of circulating T cells expressing CD25
      (interleukin 2 receptor) (P = 0.007), CD28 (P = 0.01) and CD152 (CTLA-4) (P =
      0.001). There was also a reduction in the number of circulating T cells
      expressing CD4 (P = 0.03), CD5 (P = 0.05) and CD11a (P = 0.01). There was no
      difference in the number expressing T-cell receptor alphabeta (P = 0.1), CD8 (P =
      0.4), CD54 (P = 0.4) and CD154 (P = 0.5), and the only marker expressed on a
      greater number of circulating T cells in B-CLL patients was HLA-DR (P = 0.05).
      These results suggest that there is a profound T-cell dysregulation that may
      contribute to the survival of the malignant B cells in patients with B-CLL and to
      the related autoimmune phenomena of the disease.

PMID- 11298592
TI  - Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia
      and B-cell non-Hodgkin's lymphoma treated with the UKCCSG 9003/9002 protocols.
AB  - Twenty-six children with B-cell acute lymphoblastic leukaemia (B-ALL) or Murphy
      Stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) progressed or relapsed
      after first-line therapy with a short, intensive multiagent chemotherapy regimen
      [United Kingdom Childhood Cancer Study Group (UKCCSG) 9003] (n = 62) or a
      slightly less intensive regimen (UKCCSG 9002) (n = 112). Eight patients (4.6%)
      never achieved complete remission (CR) and 18 (10.3%) relapsed. Second-line
      therapy resulted in remission for eight patients (30%). All patients initially
      treated with the 9003 protocol died. Three patients (11.5%) in the 9002 group,
      including one who never achieved CR in the primary site, are alive after second
      line therapy. This study confirms that the prognosis of relapsed or refractory B
      ALL/B-NHL is poor and exceptionally so if relapse occurred less than 6 months
      from diagnosis. High-dose therapy with stem cell rescue was used in only seven
      patients; its role needs to be studied further.

PMID- 11298593
TI  - Biological and molecular characterization of PNH-like lymphocytes emerging after
      Campath-1H therapy.
AB  - Campath-1H, an anti-CD52 monoclonal antibody, is therapeutically active in
      lymphoproliferative and autoimmune diseases. After Campath-1H therapy,
      lymphocytes with a paroxysmal nocturnal haemoglobinuria (PNH) phenotype have been
      reported to emerge. We characterized a PNH-like lymphocyte population emerging
      after Campath-1H therapy, in a patient with fludarabine refractory B-cell chronic
      lymphocytic leukaemia (B-CLL). We demonstrated a reduction in PIG-A mRNA levels
      compared with controls, and of all cytokines tested [interleukin (IL)-4, IL-13,
      IL-2, interferon(IFN)-gamma, IL-6, IL-10, and tumour necrosis factor (TNF)
      alpha], except transforming growth factor (TGF)-beta. Given the inhibitory
      activity of TGF-beta, its elevated levels may contribute to the selective
      pressure of Campath-1H, leading to the emergence of PNH-like lymphocytes.

PMID- 11298594
TI  - Sensitivity to the abl inhibitor STI571 in fresh leukaemic cells obtained from
      chronic myelogenous leukaemia patients in different stages of disease.
AB  - STI571 (CGP57148B) is an inhibitor of BCR/ABL, the cause of chronic myeloid
      leukaemia (CML). A difference exists between CML patients in chronic phase, in
      which responses to STI571are durable, and patients in blast crisis, who generally
      experience only transient responses. Leukaemic cells from six CML patients from
      whom samples could be obtained during chronic phase and at the time of blast
      crisis (BC) were compared for sensitivity to STI571, using an in vitro assay. BC
      samples showed a sensitivity similar to that obtained during chronic phase,
      suggesting that no substantial intrinsic resistance to STI571 was present in BC.

PMID- 11298595
TI  - Detection of diagnostically critical, often hidden, anomalies in complex
      karyotypes of haematological disorders using multicolour fluorescence in situ
      hybridization.
AB  - Multicolour fluorescence in situ hybridization (M-FISH) simultaneously detects
      all 24 human chromosomes in unique fluorescent colours. The identification of
      diagnostically critical gene rearrangement(s) in complex karyotypes of
      haematological disorders continues to be a challenge. We present five cases in
      which t(9;11), complex t(8;22), t(12;21) and t(11;14) were detected primarily
      using M-FISH and were confirmed using locus-specific probes. We conclude that M
      FISH can be effective in complete characterization of critical gene
      rearrangements in haematological disorders.

PMID- 11298596
TI  - Cord blood transplantation from HLA-mismatched unrelated donors as a treatment
      for children with haematological malignancies.
AB  - Factors influencing the outcome for 39 children with haematological malignancy
      who were subjected to a cord blood transplantation (CBT) from genotypically HLA
      mismatched unrelated donors were analysed. This retrospective study included 21
      children with acute lymphoblastic leukaemia, 15 with acute myelogenous leukaemia
      and one each with chronic myelogenous leukaemia, refractory anaemia with
      myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML).
      Those subjected to CBT during the first or second complete remission (CR) and MDS
      without blasts were assigned to the standard-risk (SR) group (n = 16). Patients
      in third or subsequent remission, relapse or partial remission with refractory
      leukaemia at the time of CBT were considered to be in advanced phase, and placed
      in the high-risk (HR) group (n = 11). JMML and the second CR after a relapse (n =
      8), or bone marrow failure after a rejection (n = 3), following haematopoietic
      stem cell transplantation (HSCT) in the first CR were included in the high-risk
      group. Kaplan-Meier estimates for neutrophil and platelet recovery were 83.7 +/-
      12.2 at d 60 and 55.4 +/- 16.6% at d 100 respectively. The incidence of grades II
      VI acute graft-versus-host disease was 58.5 +/- 16.8%. The Kaplan-Meier estimate
      for 3-year event-free survival (EFS) was 49.2 +/- 16.6. From multivariate
      analysis, the most important factor influencing EFS was disease status at CBT: SR
      patients had a 3-year EFS of 75.0 +/- 21.6%, compared with 29.6 +/- 20.6% for
      those with HR disease (P = 0.013, RR 4.746, 95% CI 1.382-16.298). These data
      confirm that HLA-mismatched, unrelated CBT is a feasible procedure to cure a
      significant proportion of children with leukaemia, especially if conducted in a
      favourable phase of the disease.

PMID- 11298597
TI  - The biological significance of HLA-DP gene variation in haematopoietic cell
      transplantation.
AB  - Although it has been over 25 years since HLA-DP was mapped to the major
      histocompatibility complex (MHC), its biological functions remain ill-defined. We
      sought to test the hypothesis that HLA-DP functions in a manner similar to that
      of other class II genes by measuring the risk of clinically severe grades III-IV
      acute graft-vs.-host disease (GVHD) associated with recipient HLA-DP disparity
      after haematopoietic cell transplantation. HLA-DPB1 exon 2 was sequenced in 205
      patients who underwent transplantation from HLA-A, -B, -C, -DRB1 and -DQB1 allele
      matched unrelated donors. HLA-DPB1 mismatched recipients experienced a
      significantly increased risk of acute GVHD compared with HLA-DP-identical
      transplants. Patients who were mismatched for a single HLA-DPB1 allele had an
      odds ratio (OR) of 1.0 (0.5, 2.2; P = 0.99) and patients who were mismatched for
      two alleles had an OR of 2.2 (1.0, 4.9; P = 0.06) for developing acute GVHD.
      Compared with matched and single-allele mismatched transplants, patients who were
      mismatched for two DPB1 alleles had an OR of 2.2 (1.2, 4.1; P = 0.01). HLA-DP
      plays an important role in the alloimmune response. A threshold effect of
      multiple HLA-DP disparities is evident in determining the risk of acute GVHD
      after haematopoietic cell transplantation from unrelated donors.

PMID- 11298598
TI  - Polymorphisms in the non-coding region of the human mitochondrial genome in
      unrelated plateletapheresis donors.
AB  - Human mitochondrial DNA polymorphisms are unique targets to discriminate
      nucleated cells and platelets between donor and recipient in the setting of
      transplantation or transfusion. We have previously used this approach to
      discriminate allogeneic platelets from autologous platelets after transfusion. In
      the present study, we used DNA sequencing to investigate polymorphisms present in
      two of the hypervariable segments (HVR1 and HVR2) found within the non-coding
      region of the mitochondrial genome among 100 plateletapheresis donors. Alignments
      were made with the Cambridge Reference Sequence (CRS) for human mitochondrial DNA
      (mtDNA). Combining the sequencing information of HVR1 and HVR2 we could
      demonstrate that, of the 100 investigated mtDNA samples, none was identical to
      the CRS. We found a total of 2-17 polymorphisms per donor in the investigated
      regions, most of them were basepair substitutions (563) and insertions (151). No
      deletions were found. Sixty-six of the 110 detected polymorphisms were detected
      in more than one sample. Seven polymorphisms are newly described and have not
      been published in the Mitomap database. Our results demonstrate that polymerase
      chain reaction analysis of the many polymorphisms found in the hypervariable
      region of mitochondrial DNA represents a more informative target than previously
      described mitochondrial polymorphisms for discriminating donor-recipient cells
      after transfusion or transplantation.

PMID- 11298599
TI  - Reduced memory B-cell populations in boys with B-cell dysfunction after bone
      marrow transplantation for X-linked severe combined immunodeficiency.
AB  - X-linked severe combined immunodeficiency (XSCID) is a lethal disease resulting
      in death in infancy. In many instances, haploidentical bone marrow
      transplantation (BMT) offers reconstitution of T-cell immunity alone, with
      residual hypogammaglobulinaemia. The exact nature of B-cell dysfunction in these
      patients is unclear, although differentiation arrest of the B cells is a
      potential explanation. To ascertain the differentiation status of peripheral
      blood B lymphocytes from XSCID patients after BMT, the surface expression of
      CD19, CD10, CD34, CD5, serum immunoglogulin (sIg)M, sIgD, sIgG and CD27 on these
      B cells was investigated using three-colour flow cytometry. CD27 is a marker of
      memory B cells. Populations of CD19+IgM-D- B cells, CD19+IgM-only, CD19+IgG+CD27+
      and CD19+IgM+ CD27+ B cells were found to be diminished in the XSCID patients
      after BMT with persistent hypogammaglobulinaemia, compared with both post-BMT
      patients with B-cell function and age-matched normal controls. This indicated the
      lack of CD19+IgM-D- B cells, which represent Ig isotype-switched B cells, as well
      as CD19+IgM-only and CD19+IgG+CD27+ or CD19+IgM+CD27+ memory B-cell populations.
      Interaction between CD27 and its ligand CD70 has been shown to induce IgG and IgM
      production by CD27+ B cells. Therefore, the lack of CD27/70 interaction is a
      probable explanation for the hypogammaglobulinaemia in these patients after BMT.

PMID- 11298600
TI  - Continuous complete remission in adult patients with acute lymphocytic leukaemia
      at a median observation of 12 years after autologous bone marrow transplantation.
AB  - We report our long-term experience with autologous bone marrow transplantation
      (ABMT) for 32 adult patients with acute lymphocytic leukaemia (ALL) in second or
      later remission (CR), or in first CR but with high-risk. Bone marrow was purged
      with mafosfamide (n = 25) or with immunomagnetic beads and monoclonal antibodies
      (n = 7). Retrospective analysis showed that 12 out of 32 patients were in
      continuous complete remission (CCR) at a median of 143 months (range 66-181
      months). A plateau was reached at 50 months and the disease-free and overall
      survival rates were both 37.5%. It was notable that durable CCR could be achieved
      for patients in second (three out of nine) or third (one out of six) CR. ABMT
      could produce durable CCR and the long-term outcome compared favourably with
      those reported for allogeneic transplantation.

PMID- 11298601
TI  - Characterization and localization of expression of an erythropoietin-induced
      gene, ERIC-1/TACC3, identified in erythroid precursor cells.
AB  - Gene expression profiles during erythropoietin (Epo)-induced differentiation of
      erythroid progenitor cells derived from the Friend virus anaemia (FVA) and
      phenylhydrazine (PHZ) murine models have been examined using differential display
      polymerase chain reaction (PCR). Ten cDNA fragments upregulated by Epo were
      isolated. The ribonuclease protection assay confirmed differential expression
      between Epo-stimulated and Epo-deprived cells for one of these, provisionally
      named ERIC-1. Sequencing of the full-length cDNA predicted a protein of 558 amino
      acids, 17 amino acids longer than mTACC3, the third member of a novel family of
      proteins that contain a coiled-coil domain. The human homologue, cloned using
      rapid amplification of cDNA ends (RACE)-PCR, encodes a larger protein of 838
      amino acids that is identical to hTACC3. In addition to erythroid precursor
      cells, ERIC-1/TACC3 is expressed at high levels in the testes, at moderate levels
      in the thymus and peripheral leucocytes, and at lower levels in the spleen and
      intestinal tissue. Immunohistochemical analysis using an antibody to a GST fusion
      product of the C-terminus of hERIC-1/TACC3 revealed that it is localized to
      Sertoli cells in the human testes. Confocal microscopy demonstrated hERIC-1/TACC3
      protein concentrated in the perinuclear vesicles of dermal microvascular
      endothelial cells. Although ERIC-1/TACC3 is expressed in a wide range of tissues,
      its upregulation by Epo in erythroid progenitors implies that it has a role in
      terminal erythropoiesis.

PMID- 11298602
TI  - Telomere length changes in patients with aplastic anaemia.
AB  - To investigate telomere changes in patients with aplastic anaemia (AA) and
      clinical factors influencing the telomere dynamics, telomere length (TL) was
      measured in peripheral blood mononuclear cells using Southern blot analysis of 42
      patients with AA and 39 healthy normal controls. Nineteen patients received
      supportive treatment only, while the remaining 23 patients received
      immunosuppressive therapy with anti-thymocyte globulin or anti-lymphocyte
      globulin +/- cyclosporin A. In AA patients, TL was on average 1.41 kb shorter
      than that of age-matched normal controls (P < 0.001). In patients treated with
      immunosuppression, the mean TL of non-responders was significantly shorter than
      that of age-matched normal controls (P < 0.001), while no difference in TL was
      detected in responders compared with controls. Positive correlation was observed
      between the extent of telomere shortening, the severity of neutropenia (P = 0.05)
      and the degree of mean corpuscular volume elevation (P = 0.005) at the time of
      the study. However, there was no correlation with time elapsed since diagnosis (P
      = 0.214). These findings suggest that haematopoietic stem cells in patients with
      AA rapidly lose TL at the onset of the disease. The TL shortening may reflect the
      severity of impairment of haematopoiesis.

PMID- 11298603
TI  - Intravenous immunoglobulin preparations induce mild activation of neutrophils in
      vivo via triggering of macrophages--studies in a rat model.
AB  - Despite widespread use in various immune disorders, the in vivo mechanisms of
      action of intravenous immunoglobulin (IVIG) preparations are not well known. We
      previously reported that human neutrophils degranulate after incubation with IVIG
      in vitro as a result of interaction with FcgammaRII. The purpose of this study
      was to determine whether IVIG might stimulate neutrophils in vivo. Anaesthetized
      rats received a bolus intravenous injection of IVIG preparations, containing
      either high (aged IVIG) or low (fresh IVIG) amounts or IgG dimers at a dose of
      250 mg/kg. Administration of aged IVIG induced neutrophil activation in vivo,
      whereas no effect was observed after infusion of fresh IVIG. Histological
      examination of lung tissue demonstrated mild influx of neutrophils into the
      pulmonary tissue after aged IVIG administration, though gross damage did not
      occur. Macrophage-depleted rats no longer showed activation of neutrophils after
      infusion of aged IVIG, suggesting that neutrophils become activated via an
      indirect macrophage dependent way. We conclude that IVIG induces a mild
      activation of neutrophils in vivo via triggering of macrophages depending on the
      amount of IgG dimers. For this reason, IVIG preparations with a high content of
      dimers may not always be as harmless as generally believed and may be responsible
      for some of the side-effects observed during IVIG infusions.

PMID- 11298604
TI  - Induction of Toll-like receptor 4 in granulocytic and monocytic cells
      differentiated from HL-60 cells.
AB  - Toll-like receptor 4 (TLR4) is the main protein expressed on the cell surface and
      is an essential receptor for lipopolysaccharide (LPS) signalling in human
      peripheral blood leucocytes. We examined TLR4 expression and the functional
      response to LPS in retinoic acid-treated HL-60 cells (HL-60-derived granulocytic
      cells) and interferon-gamma-treated HL-60 cells (HL-60-derived monocytic cells).
      Slight TLR4 expression was induced in HL-60-derived granulocytic cells, while
      strong induction was seen in HL-60-derived monocytic cells. LPS induced
      interleukin 1beta (IL-1beta) production and TLR4 expression in HL-60-derived
      monocytic cells, but not HL-60-derived granulocytic cells. These data indicate
      different responses to LPS in the cells. TLR4 surface expression paralleled LPS
      induced phagocytosis and TLR4-neutralizing antibody partially inhibited LPS
      induced IL-8 production in HL-60-derived monocytic cells, but not in HL-60
      derived granulocytic cells. These results suggest that HL-60-derived monocytic
      cells are partially activated via TLR4, but that HL-60-derived granulocytic cells
      are not activated via TLR4.

PMID- 11298605
TI  - Biological action of nitric oxide donor compounds on platelets from patients with
      sickle cell disease.
AB  - Several lines of evidence point to the potential role of nitric oxide (NO) in the
      pathophysiology, as well as in the therapy, of sickle cell disease (SCD). In this
      study, we compared the effects of NO on platelets from normal individuals and
      from patients with SCD. Three NO donors were used to deliver NO to platelets:
      sodium 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitrosocysteine
      (CysNO) and sodium trioxdintrate (OXINO or Angeli's salt). ADP-induced platelet
      aggregation, CD62P expression, PAC-1 binding and calcium elevation were evaluated
      in paired studies of normal and SCD subjects. DEANO significantly reduced
      aggregation in SCD platelets compared with normal platelets. DEANO similarly
      reduced the extent of CD62P expression in SCD platelets. All NO donors reduced
      PAC-1 binding, but there were no significant differences between platelets from
      normal or SCD subjects. Calcium elevation, as induced by ADP, was not altered by
      the presence of NO donors. However, when platelets were stimulated with thrombin,
      there was an increased initial response of SCD platelets compared with normal
      platelets. Taken together, these data suggest that the mode of NO delivery to
      platelets may produce various physiological responses and the optimization of NO
      delivery may contribute to reducing platelet aggregation in sickle cell disease.

PMID- 11298606
TI  - Transient adhesion refractoriness of circulating platelets under shear stress:
      the role of partial activation and microaggregate formation by suboptimal ADP
      concentration.
AB  - Exposure of whole blood (WB) to subendothelial extracellular matrix (ECM) under
      shear stress in the cone and plate(let) analyser (CPA) results in platelet
      adhesion, followed by release reaction and aggregation of circulating platelets
      on the adherent platelets. The properties of circulating non-adhered platelets in
      the CPA was studied by exposure of WB to ECM at a high shear rate (1300/s) for 2
      min (1st run), followed by transfer of the suspension to a new ECM-coated well
      for a second run (2nd run) under similar conditions. The results of the 2nd run
      demonstrated transient adhesion refractoriness associated with platelet
      microaggregate formation in the suspension. The adhesion refractoriness was
      dependent on platelet activation during the 1st run and was prevented by addition
      of apyrase (ADP scavenger) or ADP receptor inhibitor, suggesting a role for ADP
      in mediating this response. Furthermore, exposure of WB samples to suboptimal
      concentrations of ADP (0.4-1 micromol/l) or a thrombin receptor activating
      peptide (TRAP) (5 micromol/l) for 2 min resulted in a similar transient platelet
      adhesion refractoriness to ECM under flow conditions. The transient platelet
      refractoriness and microaggregate formation induced by ADP was associated with a
      transient reduction in glycoprotein (GP)Ib, increased P-selectin expression and
      increased fibrinogen binding by circulating platelets. These data suggest a role
      for platelet agonists at suboptimal concentrations in modulating platelet
      function and limiting the expansion of the thrombus.

PMID- 11298607
TI  - Lithuanian haemophilia A and B registry comprising phenotypic and genotypic data.
AB  - Haemophilia represents the most common hereditary severe bleeding disorder in
      humans. About 100 families with this condition live in Lithuania, one of the
      Baltic states with a population of 3.7 million. Haemophilia care and genetic
      counselling are still rendered difficult owing to limited availability of
      clotting factor concentrate and molecular genetic diagnosis. In the present
      study, a haemophilia registry, comprising phenotypic and genotypic data of the
      majority of Lithuanian haemophilia A and B patients, was established. The
      phenotype includes the degree of severity, factor VIII:C, factor VIII:Ag, factor
      IX:C, von Willebrand factor and antigen (VWF:RiCoF, vWF:Ag) and inhibitor status.
      Genotyping of the factor VIII and IX genes was performed using mutation screening
      methods and direct sequencing. In 61 out of 63 patients with haemophilia A
      (96.8%) and all eight patients with haemophilia B (100%), the causative mutations
      could be detected. Nineteen of the factor VIII gene defects and two of the factor
      IX gene mutations are reported for the first time. Identified mutations allowed
      direct carrier diagnosis in 83 female relatives revealing 44 carriers, 38 non
      carriers and one somatic mosaicism. The information provided by this registry
      will be helpful for monitoring the treatment of Lithuanian haemophilia patients
      and also for reliable genetic counselling of the affected families in the future.

PMID- 11298608
TI  - Safety and complications of interventional radiology for hepatocellular carcinoma
      in patients with haemophilia and cirrhosis.
AB  - Many patients with haemophilia have been chronically infected with hepatitis
      virus owing to multiple transfusions and the prevalence of hepatocellular
      carcinoma will probably increase in this population. We evaluated the safety and
      complications of radiological intervention for hepatocellular carcinoma in eight
      patients with haemophilia and cirrhosis. Radiological interventions can be
      performed safely in all patients with haemophilia. Unexpectedly, the most common
      complication was bleeding from the gastrointestinal tract. Attention should be
      paid to this potential problem in order to take appropriate steps to minimize its
      occurrence.

PMID- 11298609
TI  - Recombinant human factor VIIa in the management of amyloid-associated factor X
      deficiency.
AB  - Factor X deficiency is an important complication of amyloidosis. It is associated
      with severe bleeding that is difficult to control with plasma or prothrombin
      complex concentrates. Splenectomy ameliorates the factor X deficiency, but
      achieving satisfactory haemostasis for this operation is problematic. We report
      that a new clotting concentrate, recombinant factor VIIa, readily controls
      bleeding and makes splenectomy feasible.

PMID- 11298610
TI  - A dose of 75 microg/kg/d of i.v. anti-D increases the platelet count more rapidly
      and for a longer period of time than 50 microg/kg/d in adults with immune
      thrombocytopenic purpura.
AB  - Treatment with 75 microg/kg/d intravenous (i.v.) anti-D was compared with 50
      microg/kg/d in a prospective randomized study of 27 RhD-positive, human
      immunodeficiency virus-negative, adult, acute, non-splenectomized patients with
      immune thrombocytopenic purpura (ITP) and platelet counts < or = 30 x 109/l. The
      higher dose resulted in greater median d 1 (43 x 109/l vs. 7.5 x 109/l; P =
      0.012) and d 7 (153 x 109/l vs. 64.5 x 109/l; P = 0.001) platelet increases
      despite no greater haemoglobin decrease. Children with acute ITP receiving 75
      microg/kg/d had overnight platelet increases in seven out of nine cases. The
      duration of effect at the 75 microg/kg/d dose was 46 d vs. 21 d (P = 0.03).
      Adverse events were mild to moderate and ameliorated with prednisone and
      acetaminophen premedication.

PMID- 11298611
TI  - Use of a simplified clinical scoring system and D-dimer testing can reduce the
      requirement for radiology in the exclusion of deep vein thrombosis by over 20%.
AB  - A simplified, robust, clinical assessment, used in conjunction with a D-dimer
      assay, has been developed to identify patients with a low risk of deep vein
      thrombosis. These patients did not undergo radiological examination. The protocol
      has been used by junior doctors in a district general hospital with a
      predominantly elderly population. Four hundred and thirty-one patients with
      potential deep vein thrombosis of the lower limb were assessed using this method
      and 98 (22.7%) did not require further investigation. Of these, one was admitted
      5 months later with a pulmonary embolus. None of the other patients subsequently
      required admission for a thromboembolic event or died during a minimum of 3
      months follow-up.

PMID- 11298612
TI  - Spontaneous remission of juvenile idiopathic myelofibrosis.

PMID- 11298613
TI  - Phaeochromocytoma in pregnancy.

PMID- 11298614
TI  - Provision of long-term vascular access for haemodialysis in a patient with
      exhausted superficial arm veins.

PMID- 11298615
TI  - Dysphagia after antireflux surgery.
AB  - BACKGROUND: Dysphagia is experienced by many patients after antireflux surgery.
      This literature review examines factors associated with the development,
      prediction and management of postoperative dysphagia. METHODS: Published studies
      examining issues related to dysphagia, gastro-oesophageal reflux and
      fundoplication were reviewed. RESULTS: Postoperative dysphagia is usually
      temporary but proves troublesome for 5--10 per cent of patients. Technical
      modifications, such as a partial wrap, division of short gastric vessels and
      method of hiatal closure, have not conclusively reduced its incidence. There is
      no reliable preoperative test to predict dysphagia. CONCLUSION: It is uncertain
      whether postoperative dysphagia arises from patient predilection or is largely a
      consequence of mechanical changes created by fundoplication. Anatomical errors
      account for a significant proportion of patients referred for correction of
      dysphagia but these are uncommon in large single-institution studies. Abnormal
      manometry cannot predict dysphagia and, on current evidence, 'tailoring' the
      operation does not prevent its occurrence.

PMID- 11298616
TI  - Management of aortic aneurysm in the presence of a horseshoe kidney.
AB  - BACKGROUND: The coexistence of an aortic aneurysm and a horseshoe kidney poses a
      technical challenge to the vascular surgeon at the time of aneurysm repair. The
      aim of this review is to develop a guideline for the treatment of patients with
      this dual pathology. METHOD: A literature review combined with local experience
      provided a total of 176 cases. These were divided into two groups: asymptomatic
      aneurysms (134) and ruptured aneurysms (42), both in combination with a horseshoe
      kidney. RESULTS: Six types of operative approach were described: transperitoneal
      approach with or without separation of the renal isthmus, retroperitoneal
      approach, placement of a stent-graft, aneurysmal wrap and exploration without
      exclusion of the aneurysm. Diagnosis of the horseshoe kidney was made before
      operation in 81 per cent of patients in the asymptomatic group, and in 55 per
      cent (23 of 42) in the ruptured group. Computed tomography proved to be the most
      reliable diagnostic procedure. Occlusion of renal arteries originating from the
      aneurysm was reported in 51 per cent in the asymptomatic group, and in 74 per
      cent (23 of 31) in the ruptured group. CONCLUSION: The preferred surgical options
      for asymptomatic patients with an aortic aneurysm and a horseshoe kidney are the
      placement of a stent-graft or a retroperitoneal approach; both avoid many of the
      technical difficulties related to the presence of the horseshoe kidney. The
      approach of choice for a ruptured aneurysm is transperitoneal. Separation of the
      renal isthmus should be avoided.

PMID- 11298617
TI  - Single-blind randomized clinical trial of laparoscopic versus open appendicectomy
      in children.
AB  - BACKGROUND: Appendicectomy is the most common emergency surgical operation in
      children. The aim of this study was to compare recovery after appendicectomy
      using either a laparoscopic or an open technique in children. METHODS: Sixty-one
      children aged 4-15 years undergoing appendicectomy for suspected uncomplicated
      appendicitis were studied. The study was prospective, randomized and single
      blinded, with parallel groups. Standardized anaesthetic technique and pain
      management were used. The study endpoints were postoperative pain, need for
      rescue analgesia, and length of hospital stay. RESULTS: Children had
      significantly less pain after laparoscopic compared with open appendicectomy 8 h
      after operation and on the first and second postoperative mornings (P < 0.05).
      Laparoscopic appendicectomy resulted in a reduced requirement for rescue
      analgesia with oxycodone in hospital: mean(s.d.) 3.6(2.5) versus 5.8(3.3) doses
      (mean difference 2.2 doses, 95 per cent confidence interval (c.i.) 0.6--3.8
      doses); P = 0.01. The mean(s.d.) length of hospital stay was significantly
      shorter in the laparoscopic group: 1.9(0.7) versus 2.6(0.9) days (mean difference
      0.7 days, 95 per cent c.i. 0.3--1.1 days); P = 0.001. Three children who had open
      appendicectomy developed a wound infection. CONCLUSION: Laparoscopic
      appendicectomy is associated with less postoperative pain and a shorter hospital
      stay than open appendicectomy in children undergoing surgery for uncomplicated
      appendicitis.

PMID- 11298618
TI  - Prognostic factors and survival after hepatic resection for hepatocellular
      carcinoma without cirrhosis.
AB  - BACKGROUND: Detailed follow-up of patients with chronic hepatitis has resulted in
      increased diagnosis of hepatocellular carcinoma (HCC) in patients without
      cirrhosis. Despite numerous studies on hepatic resection, the prognostic factors
      for intrahepatic recurrence and survival are not well known for patients with HCC
      without cirrhosis. METHODS: Among 349 patients with HCC treated in the past 13
      years, cirrhosis was absent in 126 patients (36 per cent). Curative hepatic
      resection was carried out in 100 (79 per cent) of these patients. Risk factors
      for intrahepatic recurrence and prognostic factors for survival were evaluated by
      univariate and multivariate analyses. RESULTS: Postoperative morbidity and
      mortality rates were 22 and 3 per cent respectively. The 5- and 10-year disease
      free and overall survival rates were 31 and 50 per cent, and 22 and 47 per cent
      respectively. Blood loss, surgical resection margin, intrahepatic metastasis,
      portal vein invasion and extent of hepatic resection were independently
      associated with overall survival. However, the only risk factors for intrahepatic
      recurrence were portal vein invasion and hepatitis C virus (HCV) infection. The
      former was related to early recurrence while the latter was related to later
      recurrence. The 5-year disease-free survival rate was 58 per cent in patients
      with hepatitis B virus infection while it was 6 per cent in patients with HCV
      infection (P < 0.001). CONCLUSION: In the treatment of HCC without cirrhosis,
      major hepatectomy is advocated to prevent early recurrence. Liver transplantation
      may be required for patients with HCV infection.

PMID- 11298619
TI  - Sympathetic autoregulation in peripheral vascular disease.
AB  - BACKGROUND: Lower limb venous pressure increases on dependency, stimulating a
      local sympathetic axon reflex which triggers precapillary and arteriolar
      vasoconstriction. The resulting decrease in arterial calf inflow, known as the
      venoarteriolar response (VAR), is impaired in critical leg ischaemia. The aim of
      the study was to evaluate the VAR in symptomatic non-critical leg ischaemia and
      after restoration of leg perfusion following successful revascularization.
      METHODS: The study included 30 normal subjects, 30 patients with stable
      intermittent claudication and 30 patients with severe ischaemia who had undergone
      successful infrainguinal revascularization. In all patients the foot skin blood
      flow (flux) in the horizontal (HBF) and sitting (SBF) positions was measured
      using laser Doppler fluxmetry. The VAR was calculated as (HBF - SBF)/HBF x 100
      per cent. The pressure that elicited the reflex (pVAR) was evaluated in the
      horizontal position. RESULTS: The median VAR was significantly lower in patients
      with stable claudication than in normal subjects or patients following successful
      revascularization (29.1 versus 59.5 and 63.9 per cent respectively; P < 0.0001).
      Similar results were obtained for the pVAR (22 versus 45 and 40 mmHg
      respectively; P < 0.001). There was no difference, however, in either the VAR or
      pVAR between normal individuals and patients following a successful bypass.
      CONCLUSION: Patients with claudication had a significant impairment of
      orthostatic sympathetic autoregulation. After successful revascularization, and
      in spite of the extensive disease in the receiving circulation, this
      autoregulation returned to normal. Presented previously to the Vascular Surgical
      Society in London, November 1997 and published in abstract form as Br J Surg
      1998; 85: 557

PMID- 11298620
TI  - Variation in clinical decision making is a partial explanation for geographical
      variation in lower extremity amputation rates.
AB  - BACKGROUND: Rates of lower extremity amputation vary significantly both between
      and within countries. The variation does not appear to support differences in
      need as an explanation. This study set out to see if variations in clinical
      decision making might contribute to the explanation. METHODS: Based on an
      extensive audit database of lower extremity amputations and revascularization
      operations, a decision model was produced. Drawing on items in this model allowed
      the selection of six clinical cases that differed in their probability of having
      amputation as the outcome. Two cases had 80 per cent or more, two cases had 45-
      55 per cent and two cases had 20 per cent or less probability of amputation. Each
      of ten consultant vascular surgeons looked at these cases without knowledge of
      their probability of outcome and decided on amputation or revascularization.
      RESULTS: Overall the chance-adjusted level of agreement (kappa coefficient)
      between the decisions made by ten surgeons on the six clinical cases and the
      actual outcome was 0.46, indicating a moderate level of agreement. The kappa
      coefficient for individual surgeons showed complete agreement (kappa = 1) for
      four, substantial agreement (kappa = 0.66) for four, fair agreement (kappa =
      0.32) for one and no agreement other than at a chance level (kappa = 0) for one
      surgeon. CONCLUSION: Variations in the clinical decisions made by vascular
      surgeons given the same patient are likely to explain at least a part of the
      observed geographical variation in rates of lower extremity amputation. Consensus
      guidelines may enable more consistent decision making for this problem.

PMID- 11298621
TI  - Fate of hypertension after repair of coarctation of the aorta in adults.
AB  - BACKGROUND: Unrepaired aortic coarctation is known to have a detrimental effect
      on survival. The benefit of coarctation repair on systolic hypertension in adults
      has been questioned. This retrospective study was conducted to evaluate the
      impact of repair of aortic coarctation on systolic hypertension in adults.
      METHODS: Repair of aortic coarctation was performed in 84 patients aged 16-54
      (mean 29) years. All patients were hypertensive before surgical intervention
      (mean systolic blood pressure 162 mmHg; mean diastolic blood pressure 93 mmHg).
      All patients underwent echocardiography and/or cardiac catheterization. The peak
      mean systolic gradient across the coarctation was 60 mmHg. The patients were
      followed after coarctation repair for between 1 and 12 (mean 5.2) years. RESULTS:
      There was significant regression of hypertension (P < 0.001) in all patients.
      Thirty-five patients (42 per cent) did not need any antihypertensive medication 3
      months after surgery. The prevalence of hypertension at the last follow-up (after
      mean 5.2 years) was 31 per cent. CONCLUSION: Surgical repair of coarctation of
      the aorta in adults leads to regression of systolic hypertension and a decreased
      requirement for antihypertensive medication.

PMID- 11298622
TI  - Immune-stimulating effects of low-dose perioperative recombinant granulocyte
      macrophage colony-stimulating factor in patients operated on for primary
      colorectal carcinoma.
AB  - BACKGROUND: Surgery induces a postoperative immunosuppression, thereby possibly
      facilitating the outgrowth of pre-existing occult metastases or the seeding of
      disseminated tumour cells in patients with primary colorectal carcinoma operated
      on with curative intent. The hypothesis that adjuvant therapy with perioperative
      recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)
      would minimize postoperative immunosuppression was investigated in this pilot
      study. METHODS: Patients were allocated randomly to receive daily subcutaneous
      injections with either saline (n = 8) or rhGM-CSF 2.8 microg per kg body-weight
      (n = 8) from 3 days before operation until 4 days afterwards. Phytohaemagglutinin
      (PHA) skin test reactivity, monocyte human leucocyte antigen (HLA) DR expression
      and the extent of the acute-phase response, by determination of white blood cell
      count and differentiation, plasma interleukin (IL) 6 levels and body temperature
      in the perioperative period, were examined. RESULTS: rhGM-CSF treatment minimized
      postoperative suppression in PHA skin test reactivity and increased the numbers
      of neutrophils and monocytes while enhancing the expression of HLA-DR in the
      postoperative period. Additionally, both postoperative plasma IL-6 levels and the
      incidence of fever tended to be higher in the rhGM-CSF group. CONCLUSION: In this
      pilot study, perioperative administration of low-dose rhGM-CSF stimulated certain
      immune functions that are normally depressed after operation. The implications
      for the antitumour responses directly after operation and the formation of liver
      metastases are currently under investigation.

PMID- 11298623
TI  - Decreased tyrosine kinase C expression may reflect developmental abnormalities in
      Hirschsprung's disease and idiopathic slow-transit constipation.
AB  - BACKGROUND: Some patients with Hirschsprung's disease have refractory
      constipation following excision of aganglionic bowel, as do patients with
      idiopathic slow-transit constipation (STC). Gut motility depends on enteric
      neuronal development in response to expression of trophic factors and their
      receptors. Recent studies indicate the importance of neurotrophin 3 (NT-3) and
      its high-affinity receptor tyrosine kinase C (trk C) in enteric neuronal
      development. METHODS: Blinded quantitative immunohistochemical analysis of colon
      from patients with Hirschsprung's disease (aganglionic, hypoganglionic and
      normoganglionic) (n = 5), STC (n = 6) and appropriate age-matched control tissues
      (n = 5) was performed for NT-3 and trk C. Sural nerve morphometry and
      immunostaining were undertaken in three patients with STC who had abnormalities
      on limb autonomic and sensory testing. RESULTS: A significantly higher proportion
      of submucous plexus neurones was trk C immunoreactive in control infant than
      adult colon (mean(s.e.m.) 73(9) versus 16(3) per cent of the total; P < 0.001),
      in accord with a role in development. The proportion of submucous plexus trk C
      immunoreactive neurones was reduced in colon from patients with Hirschsprung's
      disease (28(7) per cent of total in normoganglionic Hirschsprung's disease; P <
      0.007 versus infant controls) and STC (10(1) per cent of total; P = 0.053 versus
      adult controls). No abnormalities of STC sural nerves were detected by
      morphometry or immunostaining. CONCLUSION: Decreased trk C expression may reflect
      developmental abnormalities in Hirschsprung's disease and idiopathic STC. Trk C
      activation by NT-3 or drugs may provide novel treatments. Presented in abstract
      form to the Pacific Association of Pediatric Surgeons, Las Vegas, Nevada, USA,
      May 2000

PMID- 11298624
TI  - Topical diltiazem ointment in the treatment of chronic anal fissure.
AB  - BACKGROUND: Chronic anal fissure has traditionally been treated surgically.
      Initial enthusiasm for chemical sphincterotomy has waned because of poor outcomes
      with glyceryl trinitrate ointment. In this study the use of topical 2 per cent
      diltiazem ointment has been investigated as an alternative method of chemical
      sphincterotomy. METHODS: A prospective assessment of 71 consecutive patients with
      a chronic anal fissure treated with 2 per cent topical diltiazem ointment for a
      median duration of 9 (range 2--16) weeks was performed. RESULTS: Fifty-one
      patients (75 per cent) experienced healing of the fissure after 2--3 months of
      treatment with topical diltiazem. Seventeen patients who did not heal were
      treated for a further 8 weeks with topical diltiazem. Eight of these patients
      subsequently healed with diltiazem. Fifty-nine of 67 patients who completed
      follow-up therefore healed on diltiazem ointment. Four patients experienced
      perianal dermatitis and one patient experienced headaches. No other side-effects
      were recorded. After a median of 32 (range 14--67) weeks' follow-up following
      completion of treatment, 27 of 41 patients available remain symptom free. Six of
      seven patients with recurrent fissure were treated successfully by repeat
      chemical sphincterotomy. CONCLUSION: Topical 2 per cent diltiazem ointment used
      as an agent for chemical sphincterotomy for chronic anal fissure offers
      significant healing rates but does not have a significant side-effect profile,
      which may aid compliance to treatment. Early recurrences are common but usually
      amenable to further chemical sphincterotomy.

PMID- 11298625
TI  - Expression of the RET proto-oncogene in papillary thyroid carcinoma and its
      correlation with clinical outcome.
AB  - BACKGROUND: In papillary thyroid carcinoma (PTC), presence of the oncogenes
      RET/PTC has been described, but their correlation with prognosis is debated. The
      aim of this study was to investigate the expression of the RET proto-oncogene
      (RET) and correlate it with clinical outcome. METHODS: Sixty-one PTCs were
      analysed for expression of RET and the oncogenes RET/PTC1-4 by polymerase chain
      reaction of complementary DNA. RESULTS: Twenty-nine PTCs (48 per cent) expressed
      the RET tyrosine kinase domain (RET-TK). Twelve expressed wild-type RET (WT-RET).
      One tumour expressed RET/PTC3, one a variant of RET/PTC3, and one RET/PTC1 and WT
      RET simultaneously. The remaining 14 expressed RET-TK only. WT-RET expression was
      detected more frequently in poorly differentiated PTCs (P < 0.05) and in PTCs
      from patients with aggressive disease (P < 0.01). WT-RET expression remained an
      independently significant risk factor for aggressive disease when analysed
      together with other recognized risk factors using a stepwise multiple logistic
      regression model. CONCLUSION: Almost half of the PTCs showed RET-TK expression;
      in only three was this explained by expression of a RET/PTC rearrangement.
      Instead, expression of WT-RET was detected in 45 per cent of the RET-TK-positive
      tumours and this expression was an independently significant risk factor for
      aggressive PTC. Presented in abstract form to the Millennium Meeting of Endocrine
      Surgeons held by the American Association of Endocrine Surgeons, British
      Association of Endocrine Surgeons and Swedish Association of Endocrine Surgeons,
      London, UK, May 2000

PMID- 11298626
TI  - Expression of gastrin in developing gastric adenocarcinoma.
AB  - BACKGROUND: A stepwise progression through premalignant stages has been
      identified for the intestinal type of gastric carcinoma. As gastrin has been
      identified as a growth factor for the intestinal type of gastric adenocarcinoma,
      the aim of this study was to investigate whether gastrin is expressed in
      premalignant gastric conditions. METHODS: Ninety archival samples of atrophic
      gastritis, intestinal metaplasia, mild gastric epithelial dysplasia, moderate
      gastric epithelial dysplasia, severe gastric epithelial dysplasia and intestinal
      type gastric adenocarcinoma were obtained. Immunocytochemistry was performed
      using antibodies directed against gastrin and its post-translational precursors,
      and the gastrin/cholecystokinin B receptor. Positive staining was identified
      using the avidin--biotin immunoperoxidase method and quantified using an image
      analysis system. RESULTS: Gastrin and its receptor were shown to be expressed in
      specimens of atrophic gastritis, intestinal metaplasia, epithelial dysplasia and
      the intestinal type of gastric carcinoma. CONCLUSION: Gastrin seems to be an
      important growth factor in gastric carcinogenesis.

PMID- 11298627
TI  - Analysis and surgical treatment of persistent dysphagia after Nissen
      fundoplication.
AB  - BACKGROUND: After Nissen fundoplication, troublesome dysphagia develops in 5-10
      per cent of patients. The mechanism of dysphagia has not been fully resolved, in
      spite of a number of studies focusing on oesophageal motility and lower
      oesophageal sphincter (LOS) dynamics. Tightness and length of the wrap have had
      considerable attention, without giving a fully satisfactory explanation of the
      pathophysiological mechanism. METHODS: Eighteen patients with persistent
      dysphagia after Nissen fundoplication needing reoperation were studied. Eighteen
      patients, matched for age and sex, without dysphagia after Nissen fundoplication
      were used as controls. Reoperation consisted of conversion of a 360 degrees into
      a 270 degrees wrap. Barium swallow, endoscopy, oesophageal manometry and 24-h pH
      monitoring were performed before and after (re)operation. RESULTS: Peristaltic
      amplitude, velocity and duration of contraction were not significantly influenced
      by operation. In 16 of 18 patients with dysphagia, LOS relaxation was incomplete
      and the residual relaxation pressure was significantly higher than that in the
      group without dysphagia (P < 0.01). No correlation was found between LOS pressure
      and peristaltic amplitude, nor between LOS pressure and ramp pressure in the
      distal oesophagus. After reoperation, basal LOS pressure decreased significantly
      (P < 0.01) and LOS relaxation was complete in all but three patients; residual
      relaxation pressure decreased (P < 0.01) and was significantly lower than that
      after uncomplicated Nissen fundoplication. In the latter group, LOS pressure,
      residual relaxation pressure and ramp pressure increased significantly after
      operation (P < 0.01). CONCLUSION: A return to complete LOS relaxation and a
      decrease in residual relaxation pressure play an important role in resolving
      dysphagia.

PMID- 11298628
TI  - Laparoscopic antireflux surgery in the treatment of the acid-sensitive
      oesophagus.
AB  - BACKGROUND: Approximately 10 per cent of patients referred for 24-h oesophageal
      pH tests with symptoms suggestive of gastro-oesophageal reflux disease will have
      a normal endoscopic examination and normal distal oesophageal acid exposure
      times, but a clear temporal correlation between their symptoms and episodes of
      acid reflux. These patients have an 'acid-sensitive oesophagus', which forms part
      of the spectrum of reflux-related conditions. Their response to antireflux
      surgery has not been reported previously. This study represents a prospective
      cohort analysis of a clearly defined group of patients with acid-sensitive
      oesophagus who have undergone laparoscopic antireflux surgery. METHODS: Nineteen
      patients (nine male and ten female; median age 32 years) underwent laparoscopic
      antireflux surgery for acid-sensitive oesophagus. All had had an incomplete
      response to medical therapy. RESULTS: Eighteen of 19 patients were graded Visick
      I or II at 6 months after operation; all 16 patients followed for 1 year were
      graded Visick I or II. There were significant falls in DeMeester symptom score
      (4.0 versus 0.5; P < 0.001), symptom events (20 versus none; P < 0.001), number
      of reflux episodes (17 versus two; P < 0.001) and overall acid exposure times
      (1.2 versus 0.3 per cent; P < 0.001) after operation. CONCLUSION: Laparoscopic
      antireflux surgery is a valid and effective treatment for patients with an acid
      sensitive oesophagus. Presented in poster form to the British Society of
      Gastroenterology, Birmingham, March 2000 and the American Gastroenterological
      Association, San Diego, May 2000

PMID- 11298629
TI  - Determinants of death following burn injury.
AB  - BACKGROUND: Burn care has changed considerably. Early surgery, nutritional
      support, improved resuscitation and novel skin replacement techniques are now
      well established. The aim of the study was to establish whether changes in
      management have improved survival following burn injury and to determine the
      contributory factors leading to non-survival. METHODS: This was a retrospective
      outcome analysis of data collected from a consecutive series of 4094 patients
      with burns admitted to a tertiary referral, metropolitan teaching hospital
      between 1972 and 1996. RESULTS: The overall mortality rate was 3.6 per cent. This
      decreased from 5.3 per cent (1972--1980) to 3.4 per cent (1993--1996) (P =
      0.076). The risk of death was increased with increasing burn size (relative risk
      (RR) 95.90 (95 per cent confidence interval 12.60--729.47) if more than 35 per
      cent of the total body surface area was burned; P < 0.001) increasing age (RR
      7.32 (3.08--17.42) if aged more than 48 years; P < 0.001), inhalation injury (RR
      3.61 (2.39--5.47); P < 0.001) and female sex (RR 1.82 (1.23--2.69); P = 0.003).
      Operative intervention (RR 0.11 (0.06--0.21); P < 0.001) and the presence of an
      upper limb burn (RR 0.53 (0.35--0.79); P = 0.002) decreased the risk. CONCLUSION:
      Modern burn care has decreased the mortality rate. Increasing burn size,
      increasing age, inhalation injury and female sex increased, while operative
      intervention and an upper limb burn decreased, the risk of death. Presented to
      the 10th Congress of the International Society for Burn Injuries, in Jerusalem,
      November 1998

PMID- 11298630
TI  - Leptin and its relation to weight loss, ob gene expression and the acute-phase
      response in surgical patients.
AB  - BACKGROUND: Patients with cachexia suffer from anorexia, weight loss and
      hypermetabolism. This study examined the relationship between plasma leptin
      concentration, leptin gene expression, weight loss and the acute-phase response
      in a group of surgical patients. METHODS: Body composition, plasma leptin,
      interleukin (IL) 6, soluble tumour necrosis factor receptor (sTNF-R) 55, sTNF-R75
      and C-reactive protein were analysed in a cohort of 28 patients undergoing
      elective surgery. Subcutaneous and omental leptin messenger RNA (mRNA) was
      analysed in a subgroup of 14 patients. RESULTS: After adjustment for fat mass
      (FM), a significant partial correlation coefficient was found between plasma
      leptin and serum IL-6 concentration (P = 0.037). A positive correlation was found
      only between plasma leptin and omental leptin mRNA (P = 0.009). Patients with an
      acute-phase response had a significantly higher level of plasma leptin per unit
      FM (P = 0.049). Stepwise multiple regression showed that FM (P < 0.0005) and
      serum IL-6 (P = 0.018) were independent predictors of plasma leptin level.
      CONCLUSION: Plasma leptin levels appear to be influenced by proinflammatory
      cytokines. Omental fat may have more influence on plasma leptin than subcutaneous
      fat. Accelerated weight loss in patients with cancer with an ongoing inflammatory
      response could be mediated in part by inappropriately high plasma levels of
      leptin.

PMID- 11298631
TI  - Hypertonic saline attenuates end-organ damage in an experimental model of acute
      pancreatitis (Br J Surg 2000; 87: 1336-40).

PMID- 11298633
TI  - Postoperative ileus: a preventable event (Br J Surg 2000; 87: 1480-93).

PMID- 11298634
TI  - Postoperative ileus: a preventable event (Br J Surg 2000; 87: 1480-93).

PMID- 11298635
TI  - Role of surgery in mild primary hyperparathyroidism in the elderly (Br J Surg
      2000; 87: 1640-49).

PMID- 11298636
TI  - Role of surgery in mild primary hyperparathyroidism in the elderly (Br J Surg
      2000; 87: 1640-49).

PMID- 11298643
TI  - Leishmania-sand fly interactions controlling species-specific vector competence.
AB  - Leishmaniasis is caused by a wide range of parasites that are transmitted by an
      even wider range of sand fly vectors. The phlebotomine vectors of Leishmaniasis
      are in some cases only permissive to the complete development of the species of
      Leishmania that they transmit in nature. The parasite-sand fly interactions that
      control this specificity are related to differences in the ability of the
      parasite to inhibit or to resist killing by proteolytic enzymes released into the
      mid-gut soon after blood feeding, and/or to maintain infection in the mid-gut
      during excretion of the digested blood meal. In each case, surface expressed or
      released phosphoglycan-containing molecules appear to promote parasite survival.
      The evidence that the surface lipophosphoglycan (LPG) mediates promastigote
      attachment to the mid-gut epithelium so as to prevent their loss during blood
      meal excretion is especially strong based on the comparison of development in
      sand flies using LPG-deficient mutants. LPG displays interspecies polymorphisms
      in their phosphoglycan domains that in most cases can fully account for species
      specific vector competence.

PMID- 11298644
TI  - Role of EspF in host cell death induced by enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) causes diarrhoea in children in
      developing countries. Many EPEC genes involved in virulence are contained within
      the locus of enterocyte effacement (LEE), a large pathogenicity island. One of
      the genes at the far righthand end of the LEE encodes EspF, an EPEC secreted
      protein of unknown function. EspF, like the other Esps, is a substrate for
      secretion by the type III secretory system. Previous studies found that an espF
      mutant behaved as wild type in assays of adherence, invasion, actin condensation
      and tyrosine phosphorylation. As EPEC can kill host cells, we tested esp gene
      mutants for host cell killing ability. The espF mutant was deficient in host cell
      killing despite having normal adherence. The addition of purified EspF to tissue
      culture medium did not cause any damage to host cells, but expression of espF in
      COS or HeLa cells caused cell death. The mode of cell death in cells transfected
      with espF appeared to be pure apoptosis. EspF appears to be an effector of host
      cell death in epithelial cells; its proline-rich structure suggests that it may
      act by binding to SH3 domains or EVH1 domains of host cell signalling proteins.

PMID- 11298645
TI  - EspA filament-mediated protein translocation into red blood cells.
AB  - Type III secretion allows bacteria to inject effector proteins into host cells.
      In enteropathogenic Escherichia coli (EPEC), three type III secreted proteins,
      EspA, EspB and EspD, have been shown to be required for translocation of the Tir
      effector protein into host cells. EspB and EspD have been proposed to form a pore
      in the host cell membrane, whereas EspA, which forms a large filamentous
      structure bridging bacterial and host cell surfaces, is thought to provide a
      conduit for translocation of effector proteins between pores in the bacterial and
      host cell membranes. Type III secretion has been correlated with an ability to
      cause contact-dependent haemolysis of red blood cells (RBCs) in vitro. As EspA
      filaments link bacteria and the host cell, we predicted that intimate bacteria
      RBC contact would not be required for EPEC-induced haemolysis and, therefore, in
      this study we investigated the interaction of EPEC with monolayers of RBCs
      attached to polylysine-coated cell culture dishes. EPEC caused total RBC
      haemolysis in the absence of centrifugation and osmoprotection studies were
      consistent with the insertion of a hydrophilic pore into the RBC membrane. Cell
      attachment and haemolysis involved interaction between EspA filaments and the RBC
      membrane and was dependent upon a functional type III secretion system and on
      EspD, whereas EPEC lacking EspB still caused some haemolysis. Following
      haemolysis, only EspD was consistently detected in the RBC membrane. This study
      shows that intimate bacteria-RBC membrane contact is not a requirement for EPEC
      induced haemolysis; it also provides further evidence that EspA filaments are a
      conduit for protein translocation and that EspD may be the major component of a
      translocation pore in the host cell membrane.

PMID- 11298646
TI  - Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repair.
AB  - The nosocomial pathogen Pseudomonas aeruginosa causes clinical infection in the
      setting of pre-existing epithelial tissue damage, an association that is mirrored
      by the increased ability of P. aeruginosa to bind, invade and damage injured
      epithelial cells in vitro. In this study, we report that P. aeruginosa inhibits
      the process of epithelial wound repair in vitro through the type III-secreted
      bacterial protein ExoT, a GTPase-activating protein (GAP) for Rho family GTPases.
      This inhibition primarily targets cells at the edge of the wound, and causes
      actin cytoskeleton collapse, cell rounding and cell detachment. ExoT-dependent
      inhibition of wound repair is mediated through the GAP activity of this bacterial
      protein, as mutations in ExoT that alter the conserved arginine (R149) within the
      GAP domain abolish the ability of P. aeruginosa to inhibit wound closure. Because
      ExoT can also inhibit P. aeruginosa internalization by phagocytes and epithelial
      cells, this protein may contribute to the in vivo virulence of P. aeruginosa by
      allowing organisms both to overcome local host defences, such as an intact
      epithelial barrier, and to evade phagocytosis by immune effector cells.

PMID- 11298647
TI  - Exoenzyme T of Pseudomonas aeruginosa elicits cytotoxicity without interfering
      with Ras signal transduction.
AB  - One virulence strategy used by the opportunistic pathogen Pseudomonas aeruginosa
      is to target toxic proteins into eukaryotic cells by a type III secretion
      mechanism. Two of these proteins, ExoS and ExoT, show 75% homology on amino acid
      level. However, compared with ExoS, ExoT exhibits highly reduced ADP-ribosylating
      activity and the role of ExoT in pathogenesis is poorly understood. To study the
      biological effect of ExoT, we used a strategy by which ExoT was delivered into
      host cells by the heterologous type III secretion system of Yersinia
      pseudotuberculosis. ExoT was found to induce a rounded cell morphology and to
      mediate disruption of actin microfilaments, similar to that induced by an ADP
      ribosylation defective ExoS (E381A) and the related cytotoxin YopE of Y.
      pseudotuberculosis. In contrast to ExoS, ExoT had no major effect on cell
      viability and did not modify or inactivate Ras by ADP-ribosylation in vivo.
      However, similar to ExoS and YopE, ExoT exhibited GAP (GTPase activating protein)
      activity on RhoA GTPase in vitro. Interestingly, ExoT(R149K), deficient for GAP
      activity, still caused a morphological change of HeLa cells. Based on our
      findings, we suggest that the ADP-ribosylating activity of ExoT target another,
      as yet unidentified, host protein that is distinct from Ras.

PMID- 11298648
TI  - Recombinant Mycobacterium tuberculosis protein associated with mammalian cell
      entry.
AB  - The ability to gain entry and resist the antimicrobial intracellular environment
      of mammalian cells is an essential virulence property of Mycobacterium
      tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1)
      in the M. tuberculosis genome promoted uptake into HeLa cells of polystyrene
      latex microspheres coated with the protein. N-terminus deletion constructs of
      Mce1 identified a domain located between amino acid positions 106 and 163 that
      was needed for this cell uptake activity. Mce1 contained hydrophobic stretches at
      the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron
      microscopy indicated that the corresponding native protein is expressed on the
      surface of the M. tuberculosis organism. The complete M. tuberculosis genome
      sequence revealed that it contained four homologues of mce (mce1, mce2, mce3,
      mce4) and that they were all located within operons composed of genes arranged
      similarly at different locations in the chromosome. Recombinant Mce2, which had
      the highest level of identity (67%) to Mce1, was unable to promote the
      association of microspheres with HeLa cells. Although the exact function of Mce1
      is still unknown, it appears to serve as an effector molecule expressed on the
      surface of M. tuberculosis that is capable of eliciting plasma membrane
      perturbations in non-phagocytic mammalian cells.

PMID- 11298649
TI  - P-fimbriae trigger mucosal responses to Escherichia coli in the human urinary
      tract.
AB  - Uropathogenic Escherichia coli elicit a host response that determines the
      severity of urinary tract infection (UTI). Specific adherence mechanisms allow
      the bacteria to initiate this process by targeting epithelial cells in the
      urinary tract mucosa. Epidemiological studies show a strong association of P
      fimbriae with disease severity, suggesting that adherence mediated by these
      organelles has a direct effect on mucosal inflammation in vivo. The present study
      examined the ability of P-fimbriae to induce inflammation in the human urinary
      tract. Patients were subjected to intravesical inoculation with a non-fimbriated
      E. coli strain or transformants of this strain expressing P-fimbriae. The
      inflammatory response was analysed as a function of P-fimbrial expression. The P
      fimbriated transformants invariably caused higher interleukin (IL)-8, IL-6 and
      neutrophil responses in the urinary tract than the ABU strain. Furthermore, loss
      of P-fimbrial expression in vivo was accompanied by a return to background levels
      of neutrophils, IL-6 and IL-8 in individual patients. The results demonstrate
      that the pap sequences confer on a non-fimbriated, avirulent strain the ability
      to induce a host response in the human urinary tract. P-fimbriae thus fulfil the
      'molecular Koch-Henle postulates' linking a single virulence factor to host
      response induction.

PMID- 11298650
TI  - The pilus-induced Ca2+ flux triggers lysosome exocytosis and increases the amount
      of Lamp1 accessible to Neisseria IgA1 protease.
AB  - The IgA1 protease secreted by the pathogenic Neisseriae cleaves Lamp1, a major
      integral membrane glycoprotein of lysosomes, and significantly reduces its steady
      state levels in an infected cell. IgA1 protease hydrolysis of Lamp1 is
      inefficient at the low pH of lysosomes, strongly suggesting that the enzyme is
      unlikely to reduce Lamp1 levels within lysosomes to any appreciable extent. We
      therefore explored the possibility that the protease may reach Lamp1 through an
      alternative route. We demonstrate that Neisseria pili induce a transient increase
      in the levels of cytosolic free Ca2+ in A431 human epithelial cells, as
      demonstrated previously for ME180 cells. This Ca2+ flux triggers lysosome
      exocytosis, quickly altering the cellular distribution of Lamp1 and increasing
      surface Lamp1 levels. Finally, we demonstrate that surface Lamp1 is cleaved by
      IgA1 protease secreted by adherent bacteria. We conclude that the pilus-induced
      Ca2+ flux increases the amount of Lamp1 that is cleavable by the IgA1 protease.

PMID- 11298651
TI  - Cellular mechanisms of microbial proteins contributing to invasion of the blood
      brain barrier.
AB  - One of the least understood issues in the pathogenesis and pathophysiology of
      microbial infection of the central nervous system (CNS) is how microorganisms
      cross the blood-brain barrier (BBB), which separates brain interstitial space
      from blood and is formed by the tight junctions of brain microvascular
      endothelial cells (BMEC). BMEC monolayer and bilayer culture systems have been
      developed as in vitro models to dissect the mechanisms of adhesion and invasion
      involved in pathogenesis of CNS infection caused by microbes. Viral, bacterial,
      fungal and parasitic pathogens may breach the BBB and enter the CNS through
      paracellular, transcellular and/or Trojan horse mechanisms. Conceivable evidence
      suggests that microbial proteins are the major genetic determinants mediating
      penetration across the BBB. Several bacterial proteins including IbeA, IbeB,
      AslA,YijP, OmpA, PilC and InlB contribute to transcellular invasion of BMEC.
      Viral proteins such as gp120 of HIV have been shown to play a role in penetration
      of the BBB. Fungal and parasitic pathothogens may follow similar mechanisms. SAG1
      of Toxoplasma gondii has been suggested as a ligand to mediate host-cell
      invasion. Understanding the fundamental mechanisms of microbial penetration of
      the BBB may help develop novel approaches to prevent the mortality and morbidity
      associated with central nervous system (CNS) infectious diseases.

PMID- 11298652
TI  - A heat labile soluble factor from Bacteroides thetaiotaomicron VPI-5482
      specifically increases the galactosylation pattern of HT29-MTX cells.
AB  - The aim of this work was to set up and validate an in vitro model to study a
      molecular response of an intestinal host cell line (HT29-MTX), to a non-pathogen
      microflora component. We found that Bacteroides thetaiotaomicron strain VPI-5482
      had the capacity to change a specific glycosylation process in HT29-MTX cells via
      a mechanism that involved a soluble factor. Differentiated HT29-MTX cells were
      grown in the presence of 20% of spent culture supernatant from the B.
      thetaiotaomicron during 10 days. Glycosylation processes were followed using a
      large panel of lectins and analysed using confocal microscopy, western blotting
      and flow cytometry techniques. Our results show that a B. thetaiotaomicron
      soluble factor modified specifically the galactosylation pattern of HT29-MTX
      cells, whereas other glycosylation steps remained mainly unaffected. Further
      characterization of this soluble factor indicates that it is a heat labile, low
      molecular weight compound. Reverse transcript-PCR (RT-PCR) analysis was unable to
      show any significant change in mRNA expression level of the main
      galactosyltransferases expressed in HT29-MTX cells. By contrast,
      galactosyltransferase activities dramatically increased in HT29-MTX cells treated
      by the soluble extract of B. thetaiotaomicron, suggesting a post-translational
      regulation of these activities. Our in vitro model allowed us to study the cross
      talk between a single bacteria and intestinal cells. The galactosylation process
      appears to be a target of this communication, thus uncovering a new window to
      study the functional consequences of co-operative symbiotic bacterial-host
      interactions.

PMID- 11298653
TI  - YopE of Yersinia, a GAP for Rho GTPases, selectively modulates Rac-dependent
      actin structures in endothelial cells.
AB  - Yersinia spp. inject effector proteins (Yersinia outer proteins, Yops) into
      target cells via a type III secretion apparatus. The effector YopE was recently
      shown to possess GAP activity towards the Rho GTPases RhoA, Rac and CDC42 in
      vitro. To investigate the intracellular, 'in vivo' targets of YopE we generated a
      Yersinia enterocolitica strain [WA(pYLCR+E)] that injects 'life-like' amounts of
      YopE as only effector. Primary human umbilical vein endothelial cells (HUVEC)
      were infected with WA(pYLCR+E) and were then stimulated with: (i) bradykinin to
      induce actin microspikes followed by ruffles as an assay for CDC42 activity
      followed by CDC42 stimulated Rac activity; (ii) sphingosine-1-phosphate to form
      ruffles by direct Rac activation; or (iii) thrombin to generate actin stress
      fibres through Rho activation. In WA(pYLCR+E)-infected HUVEC microspike formation
      stimulated with bradykinin remained intact but the subsequent development of
      ruffles was abolished. Furthermore, ruffle formation after stimulation with
      sphingosine-1-phosphate or thrombin induced production of stress fibres was
      unaltered in the infected cells. These data suggest that YopE is able to inhibit
      Rac- but not Rho- or CDC42-regulated actin structures and, more specifically,
      that YopE is capable of blocking CDC42Hs dependent Rac activation but not direct
      Rac activation in HUVEC. This provides evidence for a considerable specificity of
      YopE towards selective Rac-mediated signalling pathways in primary target cells
      of Yersinia.

PMID- 11298654
TI  - Cholera toxin and Escherichia coli enterotoxin B-subunits inhibit macrophage
      mediated antigen processing and presentation: evidence for antigen persistence in
      non-acidic recycling endosomal compartments.
AB  - Cholera toxin (Ctx) and the closely related Escherichia coli heat-labile
      enterotoxin (Etx) not only act as mediators of diarrhoeal disease but also exert
      potent immunomodulatory properties on mammalian immune systems. The toxins
      normally exert their diarrhoeagenic effects by initiating receptor-mediated
      uptake into vesicles that enter a retrograde trafficking pathway, circumventing
      degradative compartments and targeting them to the trans-Golgi network (TGN) and
      endoplasmic reticulum. Here, we examine whether receptor-mediated binding and
      cellular entry by the toxin B-subunits also lead to concomitant changes in uptake
      and trafficking of exogenous antigens that could contribute to the potent
      immunomodulatory properties of these toxins. Treatment of the macrophage (J774.2)
      cell line with Etx B-subunit (EtxB) resulted in EtxB transport to the TGN and
      also led to the formation of large, translucent, non-acidic, EtxB-devoid
      vacuoles. When exogenous antigens were added, EtxB-treated cells were found to be
      proficient in both internalization of ovalbumin (OVA) and phagocytosis of
      bacterial particles. However, the internalized OVA, instead of trafficking along
      a lysosome-directed endocytic pathway via acidified endosomes, persisted in a non
      acidic, light-density compartment that was distinct from the translucent
      vacuoles. The rerouted OVA did not co-localize with the endosomal markers rab5 or
      rab11, nor with EtxB, but was retained in a transferrin receptor-positive
      compartment. The failure of OVA to enter the late endosomal/lysosomal
      compartments correlated with a striking inhibition of OVA peptide processing and
      presentation to OVA-responsive CD4+ T-cells. CtxB also modulated OVA trafficking
      and inhibited antigen presentation. These findings demonstrate that the B
      subunits of Ctx and Etx alter the progression of exogenous antigens along the
      endocytic processing pathway, and prevent or delay efficient epitope presentation
      and T-cell stimulation. The formation of such 'antigen depots' could contribute
      to the immunomodulatory properties of these bacterial virulence determinants.

PMID- 11298655
TI  - Dendritic cells are early cellular targets of Listeria monocytogenes after
      intestinal delivery and are involved in bacterial spread in the host.
AB  - We studied the sequence of cellular events leading to the dissemination of
      Listeria monocytogenes from the gut to draining mesenteric lymph nodes (MLNs) by
      confocal microscopy of immunostained tissue sections from a rat ligated ileal
      loop system. OX-62-positive cells beneath the epithelial lining of Peyer's
      patches (PPs) were the first Listeria targets identified after intestinal
      inoculation. These cells had other features typical of dendritic cells (DCs):
      they were large, pleiomorphic and major histocompatibility complex class II(hi).
      Listeria were detected by microscopy in draining MLNs as early as 6 h after
      inoculation. Some 80-90% of bacteria were located in the deep paracortical
      regions, and 100% of the bacteria were present in OX-62-positive cells. Most
      infected cells contained more than five bacteria each, suggesting that they had
      arrived already loaded with bacteria. At later stages, the bacteria in these
      areas were mostly present in ED1-positive mononuclear phagocytes. These cells
      were also infected by an actA mutant defective in cell-to-cell spreading. This
      suggests that Listeria are transported by DCs from PPs to the deep paracortical
      regions of draining MLNs and are then transmitted to other cell populations by
      mechanisms independent of ActA. Another pathway of dissemination to MLNs was
      identified, probably involving free Listeria and leading to the infection of ED3
      positive mononuclear phagocytes in the subcapsular sinus and adjacent
      paracortical areas. This study provides evidence that DCs are major cellular
      targets of L. monocytogenes in PPs and that DCs may be involved in the early
      dissemination of this pathogen. DCs were not sites of active bacterial
      replication, making these cells ideal vectors of infection.

PMID- 11298656
TI  - Impairments in enzyme activity and biosynthesis of brush border-associated
      hydrolases in human intestinal Caco-2/TC7 cells infected by members of the Afa/Dr
      family of diffusely adhering Escherichia coli.
AB  - Wild-type diffusely adhering Escherichia coli (DAEC) harbouring afimbrial adhesin
      (Afa) or fimbrial Dr and F1845 adhesins (Afa/Dr DAEC) apically infecting the
      human intestinal epithelial cells promote injuries in the brush border of the
      cells. We report here that infection by Afa/Dr DAEC wild-type strains C1845 and
      IH11128 in polarized human fully differentiated Caco-2/TC7 cells dramatically
      impaired the enzyme activity of functional brush border-associated proteins
      sucrase-isomaltase (SI) and dipeptidylpeptidase IV (DPP IV). Blockers of the
      transduction signal molecules, previously found to be active against the Afa/Dr
      DAEC-induced cytoskeleton injury, were inactive against the Afa/Dr-induced
      decrease in sucrase enzyme activity. In parallel, Afa/Dr DAEC infection promotes
      the blockade of the biosynthesis of SI and DPP IV without affection enzyme
      stability. The observation that no changes occurred in mRNA levels of SI and DPP
      IV upon infection suggested that the decrease in biosynthesis probably resulted
      from a decrease in the translation rate. When the cells were infected with
      recombinant E. coli strains expressing homologous adhesins of the wild-type
      strains, neither a decrease in sucrase and DPP IV enzyme activities nor an
      inhibition of enzyme biosynthesis were observed. In conclusion, taken together,
      these data give new insights into the mechanisms by which the wild-type Afa/Dr
      DAEC strains induce functional injuries in polarized fully differentiated human
      intestinal cells. Moreover, the results revealed that other pathogenic factor(s)
      distinct from the Afa/Dr adhesins may play(s) a crucial role in this mechanism of
      pathogenicity.

PMID- 11298657
TI  - Benign Raeder's syndrome is probably a manifestation of carotid artery disease.
AB  - Raeder first described Horner's syndrome with ipsilateral head pain due to
      paratrigeminal organic disease, but most subsequent reports of this syndrome were
      idiopathic. Our recent case prompted a review of past reports of idiopathic
      Raeder's syndrome. Because in recent years the features of Raeder's syndrome have
      been recognized as common manifestations of carotid artery dissection, we divided
      the cases into those with and those without carotid imaging studies. The
      classifications and differential diagnoses are discussed. Sixteen cases with
      carotid imaging studies were not very different from the 28 cases without such
      studies. Most studies were performed several weeks after onset of symptoms and
      carotid dissection could not be definitely excluded in any case. In most cases of
      idiopathic Raeder's syndrome, carotid artery dissection was not considered and in
      no case was that condition definitively excluded. People with Raeder's syndrome
      not associated with a paratrigeminal organic lesion probably have a disease of
      the carotid artery. Because of the different criteria and classifications of
      Raeder's syndrome it is best to relegate this eponym to history.

PMID- 11298658
TI  - Sumatriptan: economic evidence for its use in the treatment of migraine, the
      Canadian comparative economic analysis.
AB  - The objective of this study was to evaluate economic and health effects of
      sumatriptan relative to customary therapy in Canada. The relationship between
      treatment and functionality was established based on analysis of existing data
      from a multinational study. A Monte Carlo model was developed to simulate 1 year
      for each of customary therapy and six sumatriptan formulations. Costs are
      expressed in 1998 Canadian dollars. Sumatriptan is expected to reduce the time
      spent with migraine symptoms and resulting time lost. Under customary therapy,
      the annual cost of lost time is estimated at pound908 ($1973). With sumatriptan,
      these costs ranged from pound406 ($882) with subcutaneous sumatriptan to pound577
      ($1254) with nasal sumatriptan 10 mg, saving pound331-502 ($719-1091) in the
      annual cost of time lost. All these benefits are expected to be obtained at an
      additional drug cost ranging from pound869 ($1889) for subcutaneous sumatriptan
      to pound278 ($605) for sumatriptan suppository. The cost of sumatriptan treatment
      is significantly offset by a substantial reduction of costs associated with time
      lost due to migraine symptoms.

PMID- 11298659
TI  - Analysis of Internet sites for headache.
AB  - The Internet is capable of providing an unprecedented amount of information to
      both physicians and patients interested in headache. To assess the status of
      headache information on the Internet (as of January 2000), a search for
      'headache' was performed using 10 leading Internet search engines. The number of
      web pages identified ranged from 4419 (WebCrawler) to 506 426 (Northern Light).
      The 'average' search yielded nearly 150 000 web page listings for 'headache'. The
      content was then reviewed of the top 10 listed web pages for each search (i.e. a
      total of 100 page listings). The results demonstrate that, at the present time,
      Internet-based information on headache is extensive but poorly organized.
      Editorial review of this potential valuable resource is required in order to
      maximize its utility in headache education and management.

PMID- 11298660
TI  - Frequency and predictors of physician consultations for headache.
AB  - We conducted a population-based headache questionnaire survey including questions
      on physician consultation for headache in Taipei, Taiwan from August 1997 to June
      1998. The participants comprised 3377 subjects aged > or = 15 years, of whom 328
      (9.7%) had a diagnosis of migraine and 1754 (52%) had a diagnosis of non-migraine
      headache. Migraineurs had a higher physician consultation rate (once or more in
      the past year) than the subjects with non-migraine headache (54% vs. 31%, P <
      0.0001). When frequency > or = 10 times was taken as 10 times, the analysis
      showed that migraineurs consulted physicians more often than non-migraine
      headache subjects (2.36 vs. 0.96, P = 0.04). A small proportion of the subjects
      with either migraine (12%) or non-migraine headache (6%) accounted for 50% of
      total consultations within their groups. In addition to old age, low education
      levels, living in a rural area, migrainous features (nausea and photophobia), and
      work day loss, predictors of physician consultations also included 'having been
      troubled with headache' (odds ratio (OR) = 1.7) and co-morbidity with
      hypertension (OR = 1.8) or heart disease (OR = 2.2). Low copayment and
      unrestricted access to medical care, as well as cultural factors played an
      important role in the high consultation rates in our headache subjects. Moreover,
      this study found self-perception of headache impact and co-morbid illnesses were
      important factors affecting the decision to consult physicians about headache.

PMID- 11298661
TI  - Polysomnographic findings in nights preceding a migraine attack.
AB  - Sleep recordings were performed in eight patients to analyse sleep alterations
      preceding migraine attacks. Polysomnographic recordings from nights before an
      attack were compared with nights without following migraine. We analysed standard
      sleep parameters and electroencephalogram (EEG) power spectra. The main findings
      preceding migraine attacks were a significant decrease in the number of arousals,
      a decrease in rapid eye movement (REM) density, a significant decrease of beta
      power in the slow wave sleep, and a decrease of alpha power during the first REM
      period. The results suggest a decrease in cortical activation during sleep
      preceding migraine attacks. According to the models of sleep regulation,
      alterations in the function of aminergic or cholinergic brainstem nuclei have to
      be discussed.

PMID- 11298662
TI  - Hypofunctionality of Gi proteins as aetiopathogenic mechanism for migraine and
      cluster headache.
AB  - The involvement of Gi proteins in the modulation of pain perception has been
      widely established, and mutations in G-proteins have already been identified as
      the aetiopathological cause of human diseases. The aim of the present study was
      to determine whether a deficiency or a hypofunctionality of the Gi proteins
      occurred in primary headache. The functionality and the level of expression of Gi
      proteins were investigated in lymphocytes from migraine without aura, migraine
      with aura and cluster headache sufferers. A reduced capability to inhibit
      forskolin-stimulated adenylyl cyclase activity in headache patients was observed.
      Migraine patients also showed basal adenosine cAMP levels about four times higher
      than controls. The reduced activity of Gi proteins seems not to be related to a
      reduction of protein levels since no significant reduction of the Gialpha
      subunits was observed. These results indicate Gi protein hypofunctionality as an
      aetiopathogenic mechanism in migraine and cluster headache.

PMID- 11298663
TI  - Investigations into migraine pathogenesis: time course for effects of m-CPP,
      BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat
      trigeminal nucleus caudalis (TNC).
AB  - Clinical and preclinical studies suggest that 5-HT and nitric oxide (NO)
      mobilization within the trigeminovascular system is fundamental to the initiation
      of migraine attacks., e.g. m-chlorophenylpiperazine (m-CPP) and glyceryl
      trinitrate (GTN) induce headache in humans. 5-HT2B receptors are known to mediate
      NO-dependent vasorelaxation in peripheral blood vessels, raising the possibility
      that this receptor is implicated in the pathogenesis of the disease. Therefore,
      we measured the effects of 5-HT2B agonists (m-CPP or BW723C86) or GTN on
      trigeminal nerves by quantifying Fos expression in the rat TNC. m-CPP (0.1 mg/kg,
      i.v.) induced time-dependent elevations in Fos-LI in the rat TNC 2 h and 8 h
      after injection. In contrast, neither intravenous GTN (0.5 microg/kg per min,
      infused 20 min) nor BW723C86 (0.1 mg/kg, i.v.) increased Fos-LI at 2 h or 8 h
      after administration. These data are not consistent with the involvement of the 5
      HT2B/2C receptors or NO in trigeminovascular activation, and by inference
      migraine, and suggest the contribution of some other unidentified pathway.

PMID- 11298664
TI  - Personality traits in childhood and adolescent headache.
AB  - We evaluate personality traits, anxiety and depression in a population of
      paediatric and adolescent patients, correlating personality characteristics with
      headache and sociodemographic variables. The clinical features of headache
      include specific personality traits. We report a clinical study of 57 patients
      (age 8-18 years), divided up as follows: 12 migraine with aura, 29 migraine
      without aura and 16 tension-type headache. One of Cattel's tests was administered
      to every patient; the Children's Depression Inventory test was administered to 53
      patients and the Test Anxiety Inventory test to 43 subjects. The scores obtained
      by every patient in each test were correlated with the characteristics of
      headache and with sociodemographic data. We found that patients affected by
      idiopathic headache share some personality traits, mainly emotional rigidity and
      tendency to repress anger and aggression. These traits do not seem to be
      correlated with sociodemographic data and the duration of headache: we considered
      these as characteristic of migrainous patients.

PMID- 11298665
TI  - Lack of pharmacokinetic interaction between the antimigraine compound,
      almotriptan, and propranolol in healthy volunteers.
AB  - This study was designed to assess the pharmacokinetics of almotriptan, a 5
      HT1B/1D agonist, when administered in the presence and absence of propranolol.
      Healthy male (n = 10) and female (n = 2) volunteers received (i) 80 mg
      propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii)
      12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and
      urinary almotriptan concentrations were measured by high performance liquid
      chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters
      were assessed by analysis of variance (ANOVA). Statistically significant
      differences between treatments in area under the curve (AUC), clearance, and half
      life were observed (P < 0.03), but these differences were < 7%. Ninety percent
      confidence interval analysis of log-transformed pharmacokinetic parameters showed
      that the treatments were equivalent. Adverse events were mild to moderate in
      intensity, and no treatment effects on vital signs were observed. The results
      show that propranolol has no effect on the pharmacokinetics of almotriptan.
      Concomitant administration of the two drugs is well tolerated.

PMID- 11298666
TI  - Cyclandelate in the prophylaxis of migraine: a placebo-controlled study.
AB  - The prophylactic action of cyclandelate was investigated in a multicentre,
      randomized, placebo-controlled, parallel group study. A 4-week baseline period
      was followed by a 4-week placebo phase and a 16-week treatment period with either
      1600 mg cyclandelate or placebo. Patients (n = 251) with two to six migraine
      attacks/month were randomized. Neither the primary study endpoint (reduction of
      migraine days from baseline to the last 28 days) nor most of the secondary
      endpoints (reduction in the number of migraine attacks, severity or duration of
      attacks, frequency of autonomic disturbances, medication for treatment of
      attacks) showed a difference between cyclandelate and placebo. Cyclandelate,
      however, was superior to placebo in a global impression of efficacy rated by the
      patients and the treating physicians. Both treatments were well tolerated. In
      conclusion, cyclandelate was not superior to placebo in the prophylaxis of
      migraine with regard to parameters usually used in migraine prophylaxis trials.

PMID- 11298667
TI  - First Italian case of hypnic headache, with literature review and discussion of
      nosology.

PMID- 11298668
TI  - Naratriptan prophylactic treatment in cluster headache.

PMID- 11298669
TI  - Rizatriptan wafer--sublingual vs. placebo at the onset of acute migraine.

PMID- 11298671
TI  - Recurrent thunderclap headache associated with reversible vasospasm causing
      stroke.

PMID- 11298673
TI  - Sex determination: lessons from families and embryos.
AB  - Genetic studies in familial cases of sex reversal and in human embryos have
      contributed to the understanding of human sex determination and its disorders.
      For some heritable disorders of sex reversal, the gonadal phenotype was
      frequently overlooked until sex reversal was discovered fortuitously by
      chromosome analysis, often resulting in preventable complications. Within
      families, the phenotypes are variable and, in some instances, these can be
      explained by known genetic mechanisms. When a novel molecular marker is shared by
      family members affected with sex reversal, the level of confidence is higher that
      this marker may play a role in the development of the phenotype. The
      identification of pedigrees with sufficient power to generate significant linkage
      of disorder (lod) scores from genomewide screens can now lead to the
      identification of novel sex-determining genes. Studies of the gonads of 46,XY
      human embryos have shown that SOX9 expression follows a pattern similar to that
      of SRY and, in both instances, stands in contrast to the expression observed in
      the mouse. Differences between human and mouse embryonic gonads have also been
      observed for the temporal expression of DAX1, suggesting that the mechanisms of
      action of SRY, SOX9, and DAX1 may vary between these and other species.

PMID- 11298677
TI  - Human genetic research, DNA banking and consent: a question of 'form'?

PMID- 11298678
TI  - The ethics of benefit sharing.

PMID- 11298679
TI  - Monsters, myths and syndromes depicted on stamps.

PMID- 11298681
TI  - Genetic analysis of early onset cerebellar ataxia with retained tendon reflexes
      in four Tunisian families.
AB  - Spinocerebellar ataxias comprise a poorly understood group of inherited
      degenerative neurological diseases. Attempts to classify hereditary ataxias on
      the basis of the neurological features or specific clinical signs such as tendon
      reflex changes have proven to be unsatisfactory. Early onset cerebellar ataxia
      (EOCA) is generally inherited as an autosomal-recessive trait. Thus far, we do
      not have accurate answers to several questions about its classification. However,
      significant clinical heterogeneity observed in four Tunisian families with
      typical EOCA clinical features reinforces the hypothesis of genetic heterogeneity
      underlying this phenotype. We have demonstrated that three of the four families
      studied were not linked to Friedreich's ataxia (FA), vitamin E deficiency ataxia
      (AVED), and autosomal dominant cerebellar ataxia (ADCA) loci. The fourth family
      showed homozygosity for a large pathological expansion of GAA repeat in all
      patients, the parents being heterozygous for this mutation. We have also noted,
      in the case of the family studied, that there was instability in the transmission
      of the mutation, along with a phenomenon of anticipation comparable to that
      observed in dominant triplet repeat diseases. EOCA is thus clinically
      indistinguishable from FA, yet genetically independent of all known candidate
      genes. Genetic mapping is required for research into the causal gene and an
      understanding of the disease's physiopathologic mechanisms.

PMID- 11298680
TI  - Clinical and molecular studies of a large family with desmin-associated
      restrictive cardiomyopathy.
AB  - Patients with restrictive cardiomyopathy (RC) have impaired diastolic function,
      but intact systolic function until later stages of the disease, ultimately
      leading to heart failure. Primary RC is often sporadic, but also may be inherited
      in an autosomal dominant fashion, particularly the idiopathic forms. Recently
      there has been great interest in inherited cardiomyopathy associated with myocyte
      desmin deposition ('desminopathies'). In some such families, desmin or alpha-B
      crystallin gene mutation is the underlying cause, and the desmin accumulation
      affects skeletal muscle as well, usually causing skeletal myopathy. We describe a
      large family with apparent autosomal dominant inheritance of desmin-associated RC
      spanning four generations, with the age of onset and severity/rate of progression
      being highly variable. This family is relatively unique in that there is no
      symptom-based evidence of skeletal muscle involvement, and the known desminopathy
      and cardiomyopathy genes/loci have been ruled out. These data support literature
      suggesting that desmin deposition may be associated with different underlying
      gene defects, and that a novel desminopathy gene is responsible for the condition
      in this family.

PMID- 11298682
TI  - Analysis of myocilin gene mutations in Japanese patients with normal tension
      glaucoma and primary open-angle glaucoma.
AB  - The myocilin gene was identified as a gene (MYOC) that caused primary open-angle
      glaucoma (POAG). Although a normal tension glaucoma (NTG) patient with the
      myocilin gene mutation was previously reported, no study using large numbers of
      patients with NTG has been reported. Single-strand conformation polymorphism
      analysis and subsequent sequence analysis were performed for genotyping the
      myocilin gene in 114 unrelated Japanese patients with NTG. One hundred and
      nineteen patients with POAG and 100 control subjects without glaucoma were
      studied as reference subjects. Five amino acid sequence changes of the myocilin
      were identified: Arg46Stop (one NTG), Arg76Lys (four NTG, 10 POAG, seven
      control), Arg158Gln (one NTG, one POAG, one control) found in only Japanese,
      Asp208Glu (four NTG, three POAG, one control), Pro481Ser (one control). Pro481Ser
      was novel. Arg76Lys always occurred with 1-83 from G to A in the promoter as it
      was reported in Chinese. Although some Japanese patients with NTG had sequence
      changes of the myocilin gene, there were no apparent specific mutations in
      patients with NTG.

PMID- 11298683
TI  - W44C mutation in the connexin 26 gene associated with dominant non-syndromic
      deafness.
AB  - Although more than 50% of recessive non-syndromic deafness is attributed to
      mutations in the connexin 26 (Cx26) gene, only a few reported families have shown
      dominant transmission of the trait. The W44C mutation was originally reported in
      two families from the same geographic region of France, which exhibited dominant
      non-syndromic hearing loss. In this report, we describe a third family with early
      onset severe-to-profound non-syndromic hearing loss segregating with the W44C
      mutation. Our observation places W44C among recurrent mutations in the Cx26 gene
      and emphasizes the importance of screening for this as well as other Cx26
      mutations in autosomal dominant families.

PMID- 11298685
TI  - Cryptic familial t(11;18)(q25;q23) incidentally detected by interphase FISH.
AB  - During a prospective prenatal study of numerical abnormalities of chromosomes 13,
      18, 21, X and Y using locus-specific probes, we incidentally found a case with
      only one signal for chromosome 18 per cell in a chorionic villus sampling (CVS)
      associated with an otherwise apparently normal G-banded karyotype. This led us to
      discover a cryptic t(11;18) segregating in a four-generation family. The CVS was
      performed because of mental retardation in the brother to the father of the
      fetus. A subtelomeric chromosome 18 probe revealed one signal on 18qter and one
      on 11qter of the father. Thus the father had a balanced reciprocal t(11;18) in
      spite of the apparently normal G-banded karyotype. Using the same probes, we
      found an unbalanced translocation 46,XX,-18,+der (18)t(11;18)-(q25;q23)pat in the
      fetus. Further investigation of the family showed the translocation in balanced
      and unbalanced form in four generations in mentally normal and retarded
      individuals, respectively. The study emphasizes the need for a follow-up with
      molecular cytogenetic techniques in dysmorphic and retarded children.

PMID- 11298684
TI  - Prenatal diagnosis and characterization of an unbalanced whole arm translocation
      resulting in monosomy for 18p.
AB  - Monosomy for the short arm of chromosome 18 is one of the most frequent autosomal
      deletions observed. While most cases result from terminal deletion of 18p, 16% of
      cases reported were as a result of an unbalanced whole arm translocation
      resulting in monosomy 18p. The origin and structure of these derivative
      chromosomes were reported in only a few cases. We report the prenatal diagnosis
      and characterization of a new case of monosomy 18p as a result of an unbalanced
      whole arm translocation. Amniocentesis was performed at 15 weeks of gestation on
      a 34-year-old woman initially referred for advanced maternal age.
      Holoprosencephaly was identified by ultrasound at the time of amniocentesis.
      Karyotype analysis showed an unbalanced whole arm translocation between the long
      arm of one chromosome 18 and the long arm of one chromosome 22,
      45,XX,der(18;22)(q10;q10), in all metaphases. In effect, the fetus had monosomy
      for 18p. Parental karyotypes were normal, suggesting a de novo origin for the
      der(18;22). Fluorescence in situ hybridization (FISH) analysis was performed with
      alpha-satellite probes D18Z1 and D14Z1/D22Z1 to identify the origin of the
      centromere on the der(18;22). Signal was observed with both probes, indicating
      that the centromere was composed of alpha-satellite DNA from both constituent
      chromosomes. Genotyping of the fetus and her parents with chromosome 18p STS
      marker D18S391 showed only the paternal 187 bp allele was present in the fetus,
      indicating that it was the maternal chromosome 18 involved in the der(18;22).
      This case and previous reports show that de novo unbalanced whole arm
      translocations are more likely to retain alpha-satellite sequences from the two
      chromosomes involved.

PMID- 11298686
TI  - Genetic evidence to exclude the androgen receptor co-factor, ARA70 (NCOA4) as a
      candidate gene for the causation of undermasculinised genitalia.

PMID- 11298687
TI  - Identification of the intron 14 splicing defect of the cholesteryl ester transfer
      protein gene in Hong Kong Chinese.

PMID- 11298688
TI  - A novel mutation in exon 2 of the low-density lipoprotein-receptor gene in a
      patient with homozygous familial hypercholesterolemia.

PMID- 11298689
TI  - Contact dermatitis from topical antiviral drugs.
AB  - The literature has been reviewed for contact dermatitis from topical antiviral
      drugs. 15 agents have been identified including acyclovir, imiquimod,
      podophyllin, podofilox, cidofovir, penciclovir, vidarabine, idoxuridine,
      trifluridine, tromantadine, lamivudine, interferon intralesional injections and
      ophthalmic solution, fomivirsen and foscarnet intravitreal injections and
      ganciclovir intraocular implants. Patch testing has been documented in certain
      individuals and cross-sensitization has been observed to contribute significantly
      to some allergic reactions.

PMID- 11298690
TI  - Photopatch test method: influence of type of irradiation and value of day-7
      reading.
AB  - 118 consecutive patients were photopatch tested with 5J UVA and 10mJ UVB. In
      addition, day 7 readings were taken. Testing with UVB and performing late
      readings conferred no advantage. The current recommendations of the British
      Photodermatology Group regarding photopatch testing remain the most recent guide
      to photopatch test methodology.

PMID- 11298691
TI  - The risk of active sensitization to PPD.
AB  - Para-phenylenediamine (PPD) and para-aminoazobenzene are strong sensitizers. By
      the patch test procedure, the patient may be sensitized to these agents. Combined
      testing of para-compounds may increase the risk of active sensitization. We
      studied the % of positive patch test reactions and their relevance. In order to
      assess the risk of active sensitization, we compared the % of relevant reactions
      of both early (2/3 days) and late (7 days) reactions. We also compared the
      percentage of positive patch test reactions to PPD and their relevance if
      simultaneously tested with para-aminoazobenzene. We studied the patch test
      reactions to PPD in the routine series in 2058 patients. In a group of 678
      patients we tested PPD and para-aminoazobenzene simultaneously. 4.3% and 3.1% of
      the patients reacted to PPD, respectively, with and without simultaneous testing
      with para-aminoazobenzene. We estimated the reactions as relevant in 21.1% and
      39.7%, respectively, with and without simultaneous testing with para
      aminoazobenzene. We considered none of the late reactions as relevant. We found a
      high proportion of relevant patch test reactions to PPD, but sensitization to PPD
      by the patch test procedure is a risk. We state that routine series should not
      contain PPD. The high number of irrelevant late positive reactions strongly
      suggests active sensitization. Moreover, PPD is not a ubiquitous allergen and can
      be tested on a non-routine basis if industrial exposure to para-compounds is
      suspected or if a specific localization (e.g., head or feet) prompts the testing
      of PPD. Testing PPD combined with para-aminoazobenzene does lead to a slight
      increase in positive reactions to PPD (p<0.25) and to an increase in irrelevant
      reactions (p<0.10).

PMID- 11298692
TI  - Allergic contact dermatitis from 3-iodo-2-propynyl-butylcarbamate (IPBC) - an
      update.
AB  - Results from 3 1/2 years of routine patch testing with 3-iodo-2-propynyl
      butylcarbamate (IPBC) are presented. From 1996 to 1999, a total of 3168 persons
      (2093 women and 1075 men) were patch tested with IPBC, and 7 cases were found to
      be positive. In 2 cases, sensitization could be attributed to cosmetics, and in a
      further 2 cases cosmetics were the most likely cause of sensitisation. It is
      concluded that the use of IPBC in cosmetic products can lead to contact
      sensitization and allergic contact dermatitis. 2 of the 7 reported cases with
      IPBC allergy were also found positive to thiuram, and possible cross-reactivity
      between IPBC and thiuram is discussed.

PMID- 11298693
TI  - Oral hyposensitization in patients with contact dermatitis from Parthenium
      hysterophorus.
AB  - Parthenium hysterophorus is the commonest cause of airborne contact dermatitis in
      northern India. Treatment is mostly palliative and consists of repeated courses
      of antihistamines and topical and/or systemic corticosteroids. We have evaluated
      the effect of oral hyposensitization as an alternative therapeutic modality. In
      70% of those patients who completed the study, there was a gradual improvement in
      their clinical status, as evident from a fall in their clinical severity score
      for eczema. 30% of patients had an exacerbation during the course of the study
      and hence hyposensitization in them was stopped. Patients tolerated therapy well
      and no significant side-effects were seen, except for abdominal pain, 'heartburn'
      and cheilitis.

PMID- 11298694
TI  - Diaminodiphenylmethane (DDM): frequency of sensitization, clinical relevance and
      concomitant positive reactions.
AB  - Diaminodiphenylmethane (DDM) is an aromatic diamine used in the manufacture of
      rubber, plastics, diisocyanates, dyes and adhesives. It may cross-react with para
      (amino)compounds. Allergic patch test reactions to DDM are relatively frequent,
      but their relevance is often difficult to detect. We report our experience in
      6809 patients (4589 female, 2220 male, mean age 39.9+/-17.8 years) with suspected
      contact dermatitis patch tested during the period 1997-1999 by the North-East
      Italy Contact Dermatitis Group (NEICDG). A positive patch test to DDM was
      detected in 132 (1.9%) patients (88 female, 44 male, mean age 49.5+/-16.2 years).
      Eczema was mostly localized on the hands. The relevance was detected in 31
      patients. A logistic regression analysis showed an association with patient's age
      (odds ratio 5.4 for age 30-59 years), absence of atopic diseases (odds ratio 3.1)
      and presence of leg ulcer (odds ratio 5). We found a highly significant
      correlation (p<0.001) between sensitivity to DDM and to para-phenylenediamine,
      Disperse Yellow 3, cobalt chloride, fragrance mix, benzocaine, paraben mix and
      primin. Positive patch test results to DDM were relatively frequent. The
      difficulty in detecting the relevance of these sensitizations may be related to
      the surprisingly high frequency of concomitant positive reactions to other
      allergens.

PMID- 11298696
TI  - Occupational contact dermatitis in nurses with hand eczema.
AB  - Occupationally related dermatitis is a common problem in nurses, who are exposed
      to a wide variety of allergenic and irritant substances. In a group of 44 nurses
      with hand dermatitis (40 female, 4 male), 18 were thought to have a predominantly
      allergic contact dermatitis, 15 an irritant dermatitis, 7 other form of eczema, 3
      atopic dermatitis and one pompholyx. 10 of the 15 irritant cases were diagnosed
      as occupational. Of the 18 patients with allergic contact dermatitis, the
      allergens were thought to be occupationally relevant in 8 cases. In 6 of these 8
      the dermatitis was due to natural rubber latex (3) or other rubber chemicals (3).
      2 had additional evidence of immediate-type hypersensitivity to natural rubber
      latex (one was patch test allergic to latex, the other to thiuram mix). Natural
      rubber latex allergy, both delayed and immediate, is a significant problem, and
      nurses at risk should be tested for both types of hypersensitivity, as well as
      being patch tested to standard, rubber and medicaments series.

PMID- 11298695
TI  - Prurigo pigmentosa from contact allergy to chrome in detergent.
AB  - Prurigo pigmentosa is a recurrent inflammatory dermatosis characterized by
      pruritic erythematous papules and reticulate hyperpigmentation that occurs most
      frequently in spring and summer. The etiology of prurigo pigmentosa remains
      unknown. Numerous authors have suggested that various contact allergens may be
      pathogenic or triggering factors, but nearly all attempts to identify an allergen
      have been unsuccessful. We report a case of prurigo pigmentosa induced by contact
      allergy to chrome in detergent, supporting the conclusion that contact allergens
      such as chrome may play a role in inducing prurigo pigmentosa.

PMID- 11298697
TI  - Prevention of work-related skin problems in student auxiliary nurses: an
      intervention study.
AB  - The present study was designed as an intervention study to investigate whether an
      educational programme was efficient in preventing work-related skin problems on
      the hands. 107 student auxiliary nurses (61 in the intervention group and 46 in
      the control group) were followed during the first 10 weeks of their initial
      practical training in county hospitals. The intervention group was given an
      educational programme before the practical training started. For evaluation the
      participants had questionnaires, clinical examination of the hands, measurement
      of transepidermal water loss (TEWL) and patch testing. The use of hand
      disinfectants, which was discouraged in the educational programme, was
      significantly lower in the intervention group as compared to the control group
      (p=0.002). 48% of the intervention group and 58% of the control group had
      aggravation of skin problems during practical training (p>0.05). Use of hand
      disinfectant agents was significantly associated with aggravation of skin
      problems (p=0.016). A significant increase in TEWL for the control group
      (p<0.005), but not for the intervention group, was seen after 10 weeks of
      practical training. In conclusion, the present intervention study shows promising
      results from the use of an educational programme.

PMID- 11298698
TI  - Testing with fine fragrances in eczema patients: results and test methods.
AB  - The frequencies of contact allergic reactions to 2 fine fragrances were studied
      by patch testing. Further, a comparison was made of test results before and after
      evaporation of the solvent. A total of 480 consecutive eczema patients were
      included, 100 in the Dortmund clinic and 380 in the Gentofte clinic. Patch
      testing was done with 2 international brand prestige fragrances. Each fragrance
      was tested in duplicate. One was applied immediately and the other was allowed to
      dry for 5 min before application. Testing procedures and assessment of reactions
      followed the international recommendations. In Dortmund 11% (11/100) and in
      Gentofte 5.8% (22/380) gave a positive patch test reaction to one or both of the
      fine fragrances. Assessments done in Gentofte showed that in 73% of the cases the
      positive reaction indicated a clinically relevant fragrance allergy. More
      irritant reactions were found to the wet, non-evaporated form of the fragrances
      compared with the dried form, while the method of testing did not significantly
      influence the number of positive reactions. It is recommended that patch testing
      be performed with hydro-alcoholic fragrance products after evaporation of the
      solvent.

PMID- 11298699
TI  - Allergic contact dermatitis from methoxy PEG-17/dodecyl glycol copolymer (Elfacos
      OW 100).

PMID- 11298700
TI  - The use of microdermabrasion for acne: a pilot study.
AB  - BACKGROUND: Microdermabrasion is a superficial peeling modality that has become
      quite popular with our patients and the media. OBJECTIVE: To evaluate the use of
      microdermabrasion in patients with acne. METHODS: Twenty-five patients with grade
      II-III acne were enrolled into this pilot study. All patients were under
      dermatologic care and were maintained on their acne medications throughout the
      study. Patients received eight microdermabrasion treatments at weekly intervals.
      The results were documented with before and after photographs and evaluated for
      clinical improvement. RESULTS: Twenty-four patients completed the study with 38%
      (9/24) having excellent results, 34% (8/24) with good results, 17% (4/24) with
      fair results, and 12% (3/24) with poor results. Ninety-six percent (23/24) of
      patients were pleased with their peel results and would recommend this procedure
      to others. CONCLUSION: The use of microdermabrasion in this pilot study appeared
      to produce a positive effect on the improvement of acne.

PMID- 11298701
TI  - The effects of variable pulse width of Er:YAG laser on facial skin.
AB  - BACKGROUND: The use of CO2 and Er:YAG lasers for resurfacing has increased
      significantly in the past few years. Er:YAG laser causes pinpoint bleeding during
      and after treatment with a typical pulse width of 250 microsec. A longer pulse of
      Er:YAG laser can potentially coagulate dermal blood vessels and increase the
      residual thermal damage (RTD). OBJECTIVE: To evaluate the effects of various
      pulse durations of Er:YAG laser on the depth of RTD and bleeding. METHODS: The
      preauricular skin of a volunteer was exposed to Er:YAG laser at 250-, 350-, and
      700-microsec pulse durations, with a fluence of 5 J/cm2. The number of passes
      varied between 6 and 16. The treated skin was excised and a histologic evaluation
      was done. RESULTS: The maximum depth of RTD was 50 microm and there was decreased
      bleeding with a 700-microsec pulse duration. CONCLUSION: The increased pulse
      duration of Er:YAG laser of 700 micros does not increase the maximum reported RTD
      and therefore would not change the recovery time and may have a beneficial effect
      on hemostasis.

PMID- 11298702
TI  - Laser-assisted hair transplantation: histologic comparison between CO2 and Ho:YAG
      lasers.
AB  - BACKGROUND: Various laser wavelengths and devices have been advocated for use in
      the creation of recipient channels during hair transplant surgery, including
      flash-scanned CO2, Ho:YAG (lambda = 2.12 microm), and Er:YAG (lambda = 2.94
      microm). OBJECTIVE: To determine the tissue injury caused by flash-scanned CO2
      and pulsed Ho:YAG lasers during the creation of hair transplant recipient
      channels and to assess the efficacy of the Ho:YAG laser. METHODS: Recipient
      channels were created in vivo in human scalp tissue using both lasers, and were
      excised and prepared for histologic examination. Optical micrometry of tissue
      sections was used to assess thermal injury. RESULTS: The Ho:YAG laser created
      jagged, irregular-shaped channels with larger zones of thermal injury
      (superficial deepithelialization, thermal necrosis, and thermal damage). In
      contrast, the CO2 laser produced well-defined cylindrically shaped channels free
      of cellular debris with minimal epithelial disruption and significantly less
      lateral thermal injury. CONCLUSION: Given that the Ho:YAG produced larger regions
      of thermal injury and recipient channels that were unacceptable for graft, the
      CO2 laser remains the better choice for the creation of recipient channels during
      hair transplant surgery. However, ongoing research will be necessary to determine
      the optimal laser wavelength and/or devices for this procedure.

PMID- 11298703
TI  - Subcutaneous phaeohyphomycotic cysts caused by Exophiala jeanselmei in a lung
      transplant patient.
AB  - BACKGROUND: Phaeohyphomycosis is a skin fungal infection caused by dematiaceous
      fungi that often affects immunocompromised patients. Local recurrence after
      medication or surgical treatment is common in these patients. We present a case
      in which a 42-year-old woman status post-bilateral lung transplant developed
      phaeohyphomycotic cysts with local recurrence and then was successfully treated
      by local excision with pre- and postsurgery oral itraconazole treatment.
      OBJECTIVE: To demonstrate the utility of pre- and postsurgery oral itraconazole
      in immunocompromised patients with recurrent phaeohyphomycosis. METHODS: Local
      excision with pre- and postsurgery oral itraconazole treatment. RESULTS: Simple
      excision or excision with postsurgery oral itraconazole resulted in local
      recurrence in this patient. Local excision with pre- and postsurgery oral
      itraconazole was effective in preventing the local recurrence. CONCLUSION:
      Phaeohyphomycosis can run a prolonged course in immunocompromised patients with
      multiple recurrences. Local excision with pre- and postsurgery oral itraconazole
      can be used to treat these patients with recurrent phaeohyphomycosis.

PMID- 11298705
TI  - Eyebrow transplantation.
AB  - BACKGROUND: Reconstruction of the eyebrow has historically been accomplished with
      temporal scalp pedicle flap formation or free composite scalp grafts. These two
      techniques may be associated with substantial morbidity and a false, overly dense
      eyebrow appearance. Hair transplantation of the eyebrows has been described with
      excellent results, but is relatively underreported in the literature. OBJECTIVE:
      To determine whether modern techniques of micrograft hair transplantation can
      suitably re-create an aesthetic eyebrow in a case of iatrogenic eyebrow alopecia.
      METHODS: A 33-year-old woman with iatrogenic eyebrow alopecia underwent four
      sessions of eyebrow micrograft hair transplantation to re-create both eyebrows.
      RESULTS: Suitable aesthetic eyebrows were re-created in a symmetric fashion with
      proper hair orientation. The process was time consuming and tedious, but highly
      effective. CONCLUSION: Eyebrow transplantation is a suitable alternative to
      pedicle flap formation and composite scalp grafting. It is a straightforward
      procedure that can be performed in the office under local anesthesia with minimal
      attendant morbidity. The result may be superior to that seen with more involved
      eyebrow replacement procedures.

PMID- 11298704
TI  - Treatment options for diabetic neuropathic foot ulcers: a cost-effectiveness
      analysis.
AB  - BACKGROUND: Diabetic foot ulcers are a common problem and result in more than
      85,000 lower extremity amputations each year in the United States. Studies have
      suggested that between 25% and 50% of costs related to inpatient diabetes care
      may be directly attributable to the diabetic foot. Novel treatments for these
      wounds, while expensive, have been reported to improve healing rates, although no
      formal cost effectiveness analyses have been performed in order to address the
      cost effectiveness of a given therapy. OBJECTIVE: To estimate the cost
      effectiveness of common treatment strategies for diabetic neuropathic foot
      ulcers. METHODS: Four main options are available for the treatment of diabetic
      foot ulcers: (1) standard care (SC), (2) standard treatment in a specialized
      wound care center (WCC), (3) treatment with becaplermin, (4) or treatment with
      platelet releasate (PR). We utilized effectiveness data from published clinical
      trials, meta-analyses, and a database that includes data on 26,599 patients with
      these wounds. Effectiveness was assessed as a percentage of ulcers healed at 20
      and 32 weeks. RESULTS: Baseline effectiveness (with 95% confidence intervals) for
      SC, becaplermin, PR, and WCC care were 30.9% (26.6, 35.1), 43.0% (37.3, 48.7),
      36.8% (35.4, 38.2), and 35.6% (34.8, 36.4), respectively. Cost:effectiveness
      ratios for PR versus SC and becaplermin versus SC were 414.40 and 36.59,
      respectively. Therefore the incremental cost of increasing the odds of healing by
      1% over standard therapy was $414.40 for PR and $36.59 for becaplermin.
      CONCLUSIONS: PR, becaplermin, and WCC care all provided improved healing rates
      over standard care, and becaplermin was less expensive and more effective than PR
      after 20 weeks of care.

PMID- 11298706
TI  - Generalized essential telangiectasia successfully treated with high-energy, long
      pulse, frequency-doubled Nd:YAG laser.
AB  - BACKGROUND: Generalized essential telangiectasia is a rare cutaneous disorder
      with limited therapeutic options. OBJECTIVE: To evaluate the treatment with high
      energy, high-frequency, long-pulse Nd:YAG laser in a patient with generalized
      essential telangiectasia. METHODS: A 62-year-old woman presented with a 20-year
      history of generalized essential telangiectasia. She had extensive
      telangiectasias primarily on the forearms and lower legs. The patient was treated
      with an Nd:YAG laser using a fluence of 20 J/cm2 and a pulse width of 20 msec. A
      sapphire water-cooled chill tip was used to cool the skin during laser therapy.
      The treatment was performed every 4 weeks over a period of 6 months. RESULTS:
      After six treatment sessions an almost complete clearance of telangiectatic
      lesions was observed. Side effects such as purpura, scarring, and pain did not
      occur. After a follow-up of 6 months, small telangiectatic lesions relapsed.
      CONCLUSION: Our results suggest that the Nd:YAG laser appears to be an effective
      and safe treatment option for generalized essential telangiectasia.

PMID- 11298707
TI  - Hair reduction using a scanning 800 nm diode laser.
AB  - BACKGROUND: Numerous lasers are currently available for hair removal, yet there
      are still few studies that have examined the role of fluence, light dose, hair
      color, and treatment number in laser hair reduction. OBJECTIVE: To demonstrate
      the efficacy and safety of a scanning 800 nm diode laser for hair reduction.
      METHODS: An 800 nm scanning diode laser was used to deliver 24, 38, or 48 J/cm2
      to a 3 cm x 3 cm area of skin located on the back, groin/bikini area, or thigh in
      36 adult patients with varying shades of brown or black hair. Patients received
      one to four treatments during the course of the study. Hair loss was evaluated at
      both 30 and 90 days after final treatment. Biopsies were obtained from 20
      consenting patients. RESULTS: Significant fluence-dependent hair reduction was
      demonstrated between treatment and control groups. At 48 J/cm2, the highest dose,
      a mean hair reduction of 43% was achieved 30 days after the final treatment, and
      34% was achieved 90 days after the final treatment. Darker hairs were more
      effectively treated than lighter hairs. CONCLUSIONS: Hair reduction can be safely
      and effectively achieved using a scanning 800 nm diode laser.

PMID- 11298708
TI  - Long-term results with a multiple synchronized-pulse 1064 nm Nd:YAG laser for the
      treatment of leg venulectasias and reticular veins.
AB  - BACKGROUND: The long-pulsed Nd:YAG (1064 nm) laser has been shown to be effective
      in the treatment of blue venulectasias and reticular veins. OBJECTIVE: The
      present study examined the clinical efficacy and long-term follow-up (12 months)
      of patients treated with the 1064 nm Nd:YAG laser technology. METHODS: Twenty
      five female patients (mean age 37.6 years, Fitzpatrick skin types II-V) were
      treated with up to three treatment sessions at 6-week intervals on a 5 cm2
      surface area of vessels utilizing the 1064 nm Nd:YAG laser with a circulating
      cooling device. Treatment parameters were vessel size 0.2-2.0 mm treated with a
      double pulse of 7 msec at 120 J/cm2 and vessel size 2.0-4.0 mm treated with a
      single pulse of 14 msec, fluence 130 J/cm2, with a spot size of 6 mm. Improvement
      was judged by double-blinded observer evaluation, macrophotographic imaging,
      optical chromatography, and a patient evaluation scale. RESULTS: Sixty-four
      percent of patients treated in the present study achieved 75% or greater clearing
      of vessels after a maximum of three treatment sessions. Optical chromatography
      revealed statistically significant decreased chromophore intensity (mean blueness
      reduction index of 41.2b-). Sixty-four percent of patients were greatly satisfied
      with the results of the laser treatment. Two patients manifested vessel
      recurrence when examined at 6 and 12 months, respectively. CONCLUSION: The 1064
      nm Nd:YAG laser can produce effective long-term photosclerosis of blue
      venulectasia and reticular veins. The potential for recurrence should be
      recognized by the vascular laser surgeon.

PMID- 11298709
TI  - Virtual reality simulators for dermatologic surgery: measuring their validity as
      a teaching tool.
AB  - Surgical simulation is increasingly being considered for training, testing, and
      possibly credentialing in medicine and surgery. At the University of Washington
      we have been developing a virtual reality (VR) suturing simulator. In the course
      of development it must be realized that expensive new technologies should bear
      the burden of proof of their effectiveness and reliability before they are put
      into training programs. The purpose of this article is to define the concept of
      surgical skill and to discuss how it can be measured in the context of validating
      VR surgical simulators. Specific measures of validity and reliability are
      reviewed and discussed.

PMID- 11298710
TI  - Nomenclature proposal for the zones and landmarks of the balding scalp.
AB  - BACKGROUND: Up until now there has existed no precise, agreed-upon terminology
      for referring to the areas of the balding scalp. OBJECTIVE: A standardized
      nomenclature system for the areas of the balding scalp is proposed so that
      physicians and other paraprofessionals can have a common, precise language for
      communicating with each other. METHODS: The following, in its initial form, was
      proposed to the surgical hair restoration community in the Hair Transplant Forum
      International in 1998. This final proposal includes feedback and input from those
      physicians. RESULTS: The balding scalp is divided into three major areas: the
      frontal region, the midscalp, and the vertex. Additional "subregions" are also
      defined, and long-standing landmarks of the scalp and its borders are reviewed. A
      new landmark, the "vertex transition point," is proposed, to designate that point
      in the posterior midscalp where the plane begins to change from horizontal to
      vertical. CONCLUSION: It is hoped that a universal nomenclature system for the
      scalp will facilitate communication between hair surgeons, other medical
      specialties, nonsurgical hair replacement personnel, and hair stylists.

PMID- 11298711
TI  - The efficacy of electrosurgery and excision in treating patients with multiple
      apocrine hidrocystomas.
AB  - BACKGROUND: Apocrine hidrocystomas are adenomatous cystic proliferations of the
      apocrine glands. They typically occur as solitary lesions, though rarely may
      occur as multiple lesions. Management of multiple hidrocystomas can be difficult,
      particularly if they are large. Surgical modalities may be required for effective
      therapy. OBJECTIVE: To compare the results of electrosurgery and excision in
      treating multiple apocrine hidrocystomas. METHODS: A 50-year-old man presented
      with multiple apocrine hidrocystomas ranging in size from 1 to 12 mm. The lesions
      were located over the periorbital skin, cheeks, and pinnae. Excision and
      electrodessication were utilized for therapy. At a 1-year follow-up, the patient
      was evaluated for recurrences and cosmetic result. RESULTS: There were no
      recurrences until 1 year after surgery. In the areas treated with
      electrodessication, no visible scars were identified. In the areas treated with
      excision, localized scars were observed. CONCLUSIONS: Both electrodessiation and
      excision are effective therapies for multiple apocrine hidrocystomas. We suggest
      that tumors less than 1 cm be treated with electrodessication and lesions greater
      than 1 cm with excision.

PMID- 11298712
TI  - Electrosurgery, pacemakers and ICDs: a survey of precautions and complications
      experienced by cutaneous surgeons.
AB  - BACKGROUND: Minimal information is available in the literature regarding the
      precautions implemented or complications experienced by cutaneous surgeons when
      electrosurgery is used in patients with pacemakers or implantable cardioverter
      defibrillators (ICDs). The literature pertinent to dermatologists is primarily
      based on experiences of other surgical specialties and a generally recommended
      thorough perioperative evaluation. OBJECTIVE: To determine what precautions are
      currently taken by cutaneous surgeons in patients with pacemakers or ICDs, and
      what types of complications have occurred due to electrosurgery in a dermatologic
      setting. METHODS: In the winter of 2000, a survey was mailed to 419 U.S.-based
      members of the American College of Mohs Micrographic Surgery and Cutaneous
      Oncology (ACMMSCO). RESULTS: A total of 166 (40%) surveys were returned. Routine
      precautions included utilizing short bursts of less than 5 seconds (71%), use of
      minimal power (61%), and avoiding use around the pacemaker or ICD (57%). The
      types of interference reported were skipped beats (eight patients), reprogramming
      of a pacemaker (six patients), firing of an ICD (four patients), asystole (three
      patients), bradycardia (two patients), depleted battery life of a pacemaker (one
      patient), and an unspecified tachyarrhythmia (one patient). Overall there was a
      low rate of complications (0.8 cases/100 years of surgical practice), with no
      reported significant morbidity or mortality. Bipolar forceps were utilized by 19%
      of respondents and were not associated with any incidences of interference.
      CONCLUSIONS: Significant interference to pacemakers or ICDs rarely results from
      office-based electrosurgery. No clear community practice standards regarding
      precautions was evident from this survey. The use of bipolar forceps or true
      electrocautery are the better options when electrosurgey is required. These two
      modalities may necessitate fewer perioperative precautions than generally
      recommended, without compromising patient safety.

PMID- 11298713
TI  - The use of phosphatidylcholine for correction of lower lid bulging due to
      prominent fat pads.
AB  - BACKGROUND: Patients with prominent periorbital fat pads often complain of having
      a persistent "tired" look and seek treatment from their dermatologist. OBJECTIVE:
      A non-surgical treatment of fat pads. METHODS: Thirty patients were treated for
      prominent lower eyelid fat pads with phosphatidylcholine injection. Pre- and
      posttreatment photographs were taken for long-term analysis. RESULTS: A marked
      reduction of the lower eyelid fat pads was noted over the 2-year follow-up
      period. There were no recurrences. CONCLUSION: The injection of
      phosphatidylcholine (250 mg/5 ml) into the fat pads is a simple office procedure
      that may postpone or even substitute for lower eyelid blepharoplasty.

PMID- 11298714
TI  - Factors influencing the linear depth of invasion of primary basal cell carcinoma.
AB  - BACKGROUND: Predicting subclinical growth of basal cell carcinoma (BCC) is
      important for clinicians to determine adequate surgical margins. However, few
      attempts to predict the depth of invasion of BCC prior to surgery have been done.
      OBJECTIVE: To identify the factors significantly influencing the depth of
      invasion of primary BCC. METHODS: In 235 primary BCCs treated with surgical
      excision, maximum vertical diameter, designated as "invasion index," from the
      surrounding skin surface to the bottom of the tumor was measured. Multiple linear
      regression analysis was used to identify the factors significantly influencing
      the invasion index. Seven variables including age, sex, duration, anatomic
      location, tumor horizontal diameter, histologic subtypes, and ulceration were
      entered into the model. RESULTS: Among seven variables, male sex (P = 0.0003),
      larger tumor diameter (P = 0.0011), and histologic subtypes including
      infiltrative, morpheic, and micronodular subtypes (P = 0.0019) had significant
      strength of influence for the invasion index. CONCLUSION: The three predictive
      factors positively related to the linear depth of invasion in this study are
      important, but not sufficient, considerations at planning of surgery and for
      postoperative follow-up of BCC.

PMID- 11298715
TI  - Intense pulsed light for melanocytic lesions.
AB  - BACKGROUND: Few reports about melanocytic lesion treatment using intense pulsed
      light have been published. OBJECTIVES: To evaluate the clinical results of
      diverse melanocytic lesions after treatment with an intense pulsed light source.
      METHODS: Superficial and deep melanocytic lesions were treated by an intense
      pulsed light source with the following parameters: filters of 590, 615, and 755
      nm, a fluence energy of 34-38 J/cm2, double mode, a pulse width of 3.8-4.5 msec,
      and a delay of 20 msec, at 4- to 8-week intervals. Two treatment sessions were
      applied to superficial lesions, while deep ones received four. RESULTS: A
      clearance of 76-100% (excellent) was obtained for superficial lesions such as
      ephelides, epidermal melasma, and cafe au lait macules. Nevus spilus showed good
      clinical clearance (51-75%); however, deep lesions such as nevus of Becker,
      epidermal nevus, and mixed melasma showed an average clearance of less than 25%.
      Postinflammatory hyperpigmentation was observed in melasma. CONCLUSION: Intense
      pulsed light is an effective treatment for superficial melanocytic lesions;
      however, those with a deep component improve only if repetitive treatment
      sessions are applied.

PMID- 11298717
TI  - Use of the "spiral" flap for closure of small defects of the nasal ala.
AB  - BACKGROUND: Multiple wound closure options exist for cutaneous defects of the
      nasal ala. The best option depends on the depth, size, and location of the
      defect. OBJECTIVE: To demonstrate a modification of the traditional rotation flap
      for closure of small alar defects. METHODS: The design and execution of the
      "spiral" flap for closure of a representative defect are described. RESULTS:
      Immediate and delayed postoperative views demonstrate expected outcome.
      CONCLUSION: The spiral flap modification of the rotation flap is a simple and
      elegant closure option for small nasal alar defects.

PMID- 11298716
TI  - Microcystic adnexal carcinoma: report of 13 cases and review of the literature.
AB  - BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare tumor of the skin.
      Clinically it often masquerades as a firm, subcutaneous nodule on the head and
      neck regions. Microscopically it extends far beyond assessed clinical margins
      spreading locally in the dermal, subcutaneous, and perineural tissue planes. The
      local recurrence rate by standard excision is about 50%. Recent preliminary
      reports indicate more favorable cure rates with Mohs micrographic surgery (MMS).
      OBJECTIVE: To present our data on 13 cases (12 patients) of MAC treated by MMS.
      In addition, we reviewed the medical literature to summarize the accumulated
      experience of MMS treatment in the management of MAC. We also present a case of
      bilateral MAC of the face and describe a renal transplant recipient on
      immunosuppressive therapy who developed MAC of the nasal bridge. METHODS: We
      reviewed and updated our series of MAC cases treated by MMS over the last 9
      years. A total of 13 cases of MAC are reviewed. We also searched the literature
      for MAC treated by MMS with a follow-up of more than 2-years. RESULTS: One
      patient had bilateral MAC of the nose and cheek. Another patient developed a MAC
      of the nasal bridge 20 years after renal transplantation. In this patient
      predisposing factors were radiation for teenage acne and immunosuppression
      therapy. A total of 13 cases of MAC were treated by MMS with no recurrences, with
      a mean follow-up of 5.0 years (range 1.1-8.0 years). CONCLUSION: We update the
      medical literature with 13 MAC cases treated by MMS. To our knowledge there have
      been 148 cases of MAC reported in the world literature. Including our series,
      there have been 73 cases of MAC treated with MMS. There were only four treatment
      failures. Regional and/or distant metastasis from MAC is rare, with only one
      reported death. Following MMS, the 2-year success rate was 89.7% (35 of 39). The
      accumulated data continue to confirm that when MAC is discovered early and is
      readily accessible to excision by MMS and other subspecialty support, a favorable
      outcome can be expected.

PMID- 11298718
TI  - Digital photography for mapping Mohs micrographic surgery sections.
AB  - BACKGROUND: Instant photographic print images have been used to diagram tissue
      sections excised for Mohs micrographic surgery (MMS). This approach is limited by
      the size of the print image, the potential difficulty of writing on a glossy
      photo print, and the cost of film. OBJECTIVE: We describe the use of digital
      photographic images as templates for making maps of tissue excised for MMS.
      METHODS: Digital photographic images of patients undergoing MMS are downloaded to
      a computer and printed onto plain paper. A map of the tissue excised for MMS is
      drawn directly onto the digital print. RESULTS: Several methods of creating MMS
      maps using digital photographic print images are described. CONCLUSION:
      Advantages of using digital photographs in MMS include speed of producing images,
      low cost of materials, greater accuracy of depicting the MMS excision defect, and
      ease of correlating the MMS map to the patient for subsequent stages of excision.

PMID- 11298719
TI  - Axillary basal cell carcinoma.

PMID- 11298720
TI  - De novo malignant eccrine spiradenoma with an interesting and unusual location.
AB  - BACKGROUND: Reports in the literature reveal that malignant eccrine spiradenomas
      (MES) are exceedingly rare, and represent aggressive tumors arising in long
      standing benign eccrine spiradenomas (ES). OBJECTIVE: We present a de novo case
      of MES of the nose, in contrast to reports in the literature of progression from
      long-standing benign lesions. METHODS: Case report and brief review of the
      literature. RESULTS: Our case was accepted as de novo MES because there was no
      evidence of ES on pathologic examination. It was treated by surgical excision
      with 1 cm tumor-free margins. No recurrence or complications were observed for 2
      months, but long-term follow-up could not be performed because the patient died
      of adenocarcinoma of the colon. CONCLUSION: Although previously reported lesions
      have arisen in long-standing benign ESs, usually on the trunk or extremities,
      this report shows that MES may occur as a primary malignant tumor and may occur
      in unusual locations such as the nose.

PMID- 11298721
TI  - Liporeduction by endocoagulation.
AB  - BACKGROUND: Plastic surgery and dermatologic techniques are constantly being
      improved, but clinical expression of the aging process and its surgical
      management remains a challenge. OBJECTIVE: To evaluate an alternative surgical
      approach for submandibular, mental, and periorbital loose tissue treatment.
      METHODS: We present a modified transcutaneous bipolar diathermy microprobe using
      the coaxial principle for the treatment of mental, submandibular, and periorbital
      loose tissue. RESULTS: The outcome was evaluated as satisfactory for the
      following reasons: lower morbidity, it is a simple time-saving surgical
      technique, no healing difficulties, less dehiscence, no wound exposure, minimal
      incisions, and a faster postoperative recovery with a simple wound care.
      CONCLUSION: We suggest that this procedure is a simple surgical approach that
      delays extensive plastic surgery.

PMID- 11298722
TI  - Animal experimentation.

PMID- 11298723
TI  - Regarding treatment of gunpowder traumatic tattoos.

PMID- 11298724
TI  - Regarding sentinel lymph node biopsy.

PMID- 11298727
TI  - Antilipolytic drugs for the prevention of primary ventricular fibrillation.

PMID- 11298728
TI  - Anti-retroviral therapy, insulin resistance and lipodystrophy.

PMID- 11298729
TI  - Differential effects of short and long duration insulinotropic agents on meal
      related glucose excursions.
AB  - AIM: Abnormal beta-cell function, characterized as the inability of the beta-cell
      to mount a rapid secretory response to glucose, is a well-established pathology
      of type 2 diabetes mellitus. These studies were designed to demonstrate the
      importance of early insulin release on the control of meal-induced glucose
      excursions by capitalizing on the significant pharmacodynamic differences between
      several oral insulin secreting agents. METHODS: Male Sprague Dawley fitted with
      indwelling jugular cannulas were used to compare the pharmacodynamic profiles of
      nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent
      blood samples following the administration of these compounds via oral gavage. In
      similar animals which were pretrained to consume their daily food intake in two
      discrete 45-min meals, the effects of compound induced changes in pre-meal, meal
      and post-meal insulin profiles on glycaemic control were assessed through
      frequent blood sampling following the administration of these compounds 10 min
      prior to a 30-min meal. RESULTS: There were significant pharmacodynamics
      differences between the three oral agents tested and the time to elicit peak
      insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to
      Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre
      meal insulin levels and glucose excursions paralleled those in the control.
      Conversely, the other three agents, at doses that produced hypoglycaemic
      responses of similar magnitude, all increased early insulin release (Delta AUC(
      15 to 3 min) = 0.5 +/- 0.01, 1.6 +/- 0.4, 3.6 +/- 0.0, 1.2 +/- 0.1 and 1.73 +/-
      0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag,
      respectively) and curbed glucose excursions during the meal at varying rates and
      degrees (Delta AUC(0--30 min) = 39 +/- 6, 8 +/- 7, 5 +/- 7, - 1 +/- 8 and - 3 +/-
      8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively).
      However, unlike Nateg, the longer duration of action of Repag and Glip elicited
      sustained post-meal relative hypoglycaemia. CONCLUSION: These data support the
      impact of early and rapid insulin release in the control of prandial and post
      meal glycaemia and demonstrate that a short anticipatory burst of insulin,
      restricted to the beginning of a meal, provides a clear metabolic advantage and
      prevents post-meal hypoglycaemic episodes when compared to a greater but reactive
      insulin exposure that follows a meal-induced increase in glucose excursion.

PMID- 11298730
TI  - Early insulin release effectively improves glucose tolerance: studies in two
      rodent models of type 2 diabetes mellitus.
AB  - AIM: Islet dysfunction, characterized by the loss of an acute insulin secretory
      response (AIR) to glucose is a well-established pathology of type 2 diabetes
      mellitus. Using oral insulin secreting agents with very different pharmacodynamic
      profiles, the present study was undertaken to test the hypothesis that, within
      the setting of an underlying insulin resistance, changes in the insulin response
      profile can differentially affect glycaemic control. METHOD: The mildly insulin
      resistant high-fat fed Sprague Dawley (HF) rat and the very insulin resistant
      Zucker fatty (fa/fa) rat, chronically fitted with indwelling jugular cannula were
      subjected to an oral glucose load. Compounds were administered 5 min before the
      oral glucose load. Nateglinide (Nateg) was administered to elicit only an early
      insulin secretory response and glipizide (Glip) to elicit a later but greater
      insulin secretory response. Acetaminophen was used as a marker to assess for
      potential effects of these compounds on gastric emptying rates. RESULTS: Nateg
      rapidly increased early insulin release (from -5 to 0) while the effects on total
      insulin release were similar to those in the controls and glucose excursions were
      eliminated in both diabetic models with no evidence of sustained hypoglycaemia.
      Conversely, Glip did not affect early insulin release but increased total insulin
      release (- 15 to 120 min), but only after the oral glucose load. Glip partially
      curbed glucose excursions in the mildly insulin resistant HF rodent and was
      totally ineffective in the very insulin resistant Zucker rat. The differential
      effects could not be attributed to effects on gastric emptying rates. CONCLUSION:
      These data support the importance of early insulin release in type 2 diabetes
      mellitus and indicate that, independent of the level of insulin resistance,
      stimulating insulin release early and briefly provides for more effective and
      tighter glycaemic control than increasing insulin exposure to a greater magnitude
      later.

PMID- 11298731
TI  - Impressive lipid changes following hypolipidaemic drug administration can unveil
      subclinical hyperthyroidism.
AB  - It is well known that thyroid hormones modulate lipoprotein metabolism. Thus, the
      presence of clinical or subclinical hyperthyroidism may influence lipid
      parameters of dyslipidaemic patients and the efficacy of hypolipidaemic therapy.
      Here we present a patient with mixed hyperlipidaemia whose impressive improvement
      of his lipid profile following ciprofibrate administration pointed towards the
      diagnosis of asymptomatic underlying subclinical hyperthyroidism.

PMID- 11298732
TI  - Effects of the Magenstrasse and Mill operation for obesity on plasma leptin and
      insulin resistance.
AB  - BACKGROUND: We evaluated the effect of the Magenstrasse and Mill (M & M)
      operation--a new form of non-banded vertical gastroplasty-on weight loss, plasma
      leptin levels and insulin resistance. METHODS: Fasting plasma glucose, leptin and
      insulin levels were measured in 12 normal controls, 39 morbidly obese patients
      and 39 patients a median 3 years after the M & M procedure. Insulin resistance
      was calculated by the homeostasis model insulin resistance index. RESULTS: Body
      mass index mean (s.d.) decreased significantly (p < 0.0001), from 48(7) to 33(5)
      kg/m2, after the M & M procedure. Fasting plasma leptin concentration in the
      morbidly obese group was 37.9(15.4) ng/ml, significantly (p < 0.0001) higher than
      the control group (12.2(8.4)) and the M & M group (19.1(12.7)) ng/ml. Fasting
      plasma insulin concentrations were also significantly (p < 0.0001) higher in the
      morbidly obese group compared with than in the M & M group or in the control
      group: 35.5(22.3) mU/l, 15.5(7.1) mU/l and 13.6(3.4) mU/l, respectively. Insulin
      resistance was 9.6(7.2) in the morbidly obese group and 3.5(1.9) in the M & M
      group (p < 0.0001). CONCLUSION: This is one of the first studies to show that the
      decrease in insulin resistance after weight loss achieved by anti-obesity surgery
      is associated with significantly lower levels of plasma leptin.

PMID- 11298733
TI  - Lack of postprandial leptin peaks in patients with type 2 diabetes mellitus.
AB  - Leptin production by the adipocyte is acutely stimulated by insulin in vitro. In
      normal individuals, postprandial insulin peaks are not accompanied by
      corresponding changes in circulating leptin. Postprandial regulation of leptin in
      individuals with type 2 diabetes, to our knowledge, has not been previously
      examined in detail. We examined the effect of meals on circulating leptin levels
      in six patients with type 2 diabetes who were not treated with insulin and in
      seven normal individuals. After informed consent was obtained, all subjects were
      admitted to the General Clinical Research Center for 6 days. They consumed four
      meals daily (breakfast, lunch, dinner and snack). Eighteen blood samples were
      drawn between 7.40 a.m. and midnight for the determination of serum leptin,
      insulin and glucose levels. Postprandial peaks were clearly identifiable for
      glucose and insulin levels both in normal subjects and in those with type 2
      diabetes. However, no postprandial peaks of leptin levels were present.
      Correlation analysis demonstrated a lack of correlation between leptin levels and
      the levels of glucose or insulin. We conclude that, in spite of the presence of
      postprandial insulin peaks, there are no acute changes in circulating leptin
      levels postprandially in patients with type 2 diabetes who are not on insulin
      therapy. In this regard, in-vivo regulation of leptin by meals in patients with
      type 2 diabetes is similar to that in normal individuals.

PMID- 11298734
TI  - Carbohydrate depletion has profound effects on the muscle amino acid and glucose
      metabolism during hyperinsulinaemia.
AB  - AIM: We investigated the effect of carbohydrate availability and euglycaemic
      hyperinsulinaemia on intramuscular and plasma amino acids in 14 healthy men (age
      26.5 +/- 0.9 years, b.m.i. 22.9 +/- 0.5 kg/m2). METHODS: Insulin was infused (1.5
      mU/kg/min) for 240 min both after a carbohydrate depleting exercise and after
      carbohydrate loading. Muscle samples were taken before and after
      hyperinsulinaemia. Plasma and intramuscular amino acid concentrations were
      measured. RESULTS: Insulin-mediated glucose disposal was similar after
      carbohydrate depletion (65.2 +/- 1.9 micromol/kg/min) and loading (66.9 +/- 2.8
      micromol/kg/min). Carbohydrate depletion was associated with decreased alanine
      and increased branched chain amino acid (BCAA) concentrations in muscle and
      plasma. Blood lactate was lower after carbohydrate depletion (477 +/- 25
      micromol/l) than loading (850 +/- 76 micromol/l, p < 0.001). In carbohydrate
      depletion, hyperinsulinaemia resulted in a greater increase in intramuscular
      (from 927 +/- 48 nmol/g muscle to 2029 +/- 104 nmol/g muscle, p < 0.001), than
      plasma (from 197 +/- 6.7 micromol/l to 267 +/- 11 micromol/l, p < 0.001) alanine.
      After carbohydrate loading muscle alanine did not rise significantly (from 1546
      +/- 112 nmol/g muscle to 1781 +/- 71 nmol/g muscle) whereas plasma alanine
      decreased (from 339 +/- 26 micromol/l to 272 +/- 13 micromol/l, p < 0.05).
      CONCLUSIONS: (1) Carbohydrate availability has profound effects on the
      interrelationship between glucose and amino acid metabolism and on the form of
      storage for glucose-derived carbons. (2) For most amino acids changes in plasma
      levels of amino acids are not related to changes in concentrations of
      intramuscular amino acids during hyperinsulinaemia.

PMID- 11298735
TI  - The oxidative mechanism of heparin interferes with radical production by glucose
      and reduces the degree of glycooxidative modifications on human serum albumin.
AB  - Among substances which may prove useful in preventing or reducing the progression
      of glycooxidative modifications of proteins, heparin plays a unique role. To
      elucidate the mechanism whereby heparin may favourably influence the protein
      structure during glycation, human serum albumin (HSA) was glycated with both 25
      and 50 mM glucose in the absence and presence of 12 microg.mL(-1) low-molecular
      mass heparin. Glycation caused: (a) modifications of fluorescence emission and
      excitation spectra consistent with the covalent attachment of glucose to protein;
      (b) a significant increase in the esterase activity of HSA on p-nitrophenyl
      acetate; (c) a reduced susceptibility to tryptic digestion and (d) enhanced
      formation of high-molecular mass aggregates of HSA. These alterations were
      accompanied by oxidative reactions, as the EPR spectra showed a clear-cut radical
      signal, dependent on glucose concentration, further confirmed by measurement of
      the carbonyl content of HSA, as an indirect proof of oxidative damage. In the
      presence of heparin all the above alterations, especially at 25 mM glucose,
      turned out to be antagonized. The effects of heparin were dependent on its
      specific binding to HSA, which triggered an oxidative mechanism strikingly
      different from that caused by glucose. In the presence of heparin, only the
      radical species catalyzed by heparin was detected across all samples of glycated
      HSA, irrespective of glucose concentration. In addition, at 25 mM glucose,
      enhancement of the oxidative capacity of heparin was also observed. The results
      demonstrate that the oxidative mechanism sustained by heparin mediates biological
      effects that may be beneficial in reducing the extent of glycooxidative damage on
      HSA.

PMID- 11298736
TI  - Site-directed mutagenesis of human membrane-associated ganglioside sialidase:
      identification of amino-acid residues contributing to substrate specificity.
AB  - Unlike microbial sialidases, mammalian sialidases possess strict substrate
      specificity, for example the human membrane-associated sialidase, which
      hydrolyzes only gangliosides. To cast light on the molecular basis of this narrow
      substrate preference, predicted active site amino-acid residues of the human
      membrane sialidase were altered by site-directed mutagenesis. When compared with
      the active site amino-acid residues proposed for Salmonella typhimurium
      sialidase, only five out of 13 residues were found to be different to the human
      enzyme, these being located upstream of the putative transmembrane region.
      Alteration of seven residues, including these five, was followed by transient
      expression of the mutant enzymes in COS-1 cells and characterization of their
      kinetic properties using various substrates. Substitution of glutamic acid (at
      position 51) by aspartic acid and of arginine (at position 114) by glutamine or
      alanine resulted in retention of good catalytic efficiency toward ganglioside
      substrates, whereas other substitutions caused a marked reduction. The mutant
      enzyme E51D exhibited an increase in hydrolytic activity towards GM2 as well as
      sialyllactose (which are poor substrates for the wild-type) with change to a
      lower Km and a higher Vmax. R114Q demonstrated a substrate specificity shift in
      the same direction as E51D, whereas R114A enhanced the preference for
      gangliosides GD3 and GD1a that are effectively hydrolyzed by the wild-type. The
      inhibition experiments using 2-deoxy-2,3-didehydro-N-acetylneuraminic acid were
      consistent with the results in the alteration of substrate specificity. The
      findings suggest that putative active-site residues of the human membrane
      sialidase contribute to its substrate specificity.

PMID- 11298737
TI  - Assembly and clustering of acetylcholine receptors containing GFP-tagged epsilon
      or gamma subunits: selective targeting to the neuromuscular junction in vivo.
AB  - Acetylcholine receptor (AChR) gamma and epsilon subunits were tagged by green
      fluorescent protein (GFP) to analyse assembly and targeting in live muscle fibers
      at the neuromuscular junction. N- or C-terminal fusion polypeptides showed no
      fluorescence upon transfection of HEK cells. When GFP was inserted into the
      cytoplasmic loop connecting putative transmembrane regions M3 and M4, the
      gamma/GFP and epsilon/GFP subunits were fluorescent and formed together with the
      alpha, beta, and delta subunits GFP-tagged AChR complexes that were integrated
      into the plasma membrane. As the AChR were also clustered by rapsyn, the results
      indicate that the cytoplasmatic domains of the gamma and epsilon subunits may not
      be required for assembly and rapsyn-dependent clustering. The gamma/GFP and
      epsilon/GFP subunit-containing receptors were expressed in X. laevis oocytes and
      have affinities for acetylcholine similar to that of the wild-type receptors.
      Direct gene transfer into single muscle fibers reveals that gamma/GFP or
      epsilon/GFP polypeptides are expressed at the site of injection and are
      transported within the endoplasmatic reticulum. When reaching subsynaptic
      regions, both gamma/GFP or epsilon/GFP subunits compete with endogenous epsilon
      subunits to assemble GFP-tagged receptors, which are selectively targeted to the
      postsynaptic membrane.

PMID- 11298738
TI  - Cytoplasmic surface structure of bacteriorhodopsin consisting of interhelical
      loops and C-terminal alpha helix, modified by a variety of environmental factors
      as studied by (13)C-NMR.
AB  - We have examined the (13)C-NMR spectra of [3-(13)C] Ala-labeled bacteriorhodopsin
      and its mutants by varying a variety of environmental or intrinsic factors such
      as ionic strength, temperature, pH, truncation of the C-terminal alpha helix, and
      site-directed mutation at cytoplasmic loops, in order to gain insight into a
      plausible surface structure arising from the C-terminal alpha helix and loops. It
      is found that the surface structure can be characterized as a complex stabilized
      by salt bridges or metal-mediated linkages among charged side chains. The surface
      complex in bacteriorhodopsin is most pronounced under the conditions of 10 mM
      NaCl at neutral pH but is destabilized to yield relaxed states when environmental
      factors are changed to high ionic strength, low pH and higher temperature. These
      two states were readily distinguished by associated spectral changes, including
      suppressed (cross polarization-magic angle spinning NMR) or displaced (upfield)
      (13)C signals from the C-terminal alpha helix, or modified spectral features in
      the loop region. It is also noteworthy that such spectral changes, when going
      from the complexed to relaxed states, occur either when the C-terminal alpha
      helix is deleted or site-directed mutations were introduced at a cytoplasmic
      loop. These observations clearly emphasize that organization of the cytoplasmic
      surface complex is important in the stabilization of the three-dimensional
      structure at ambient temperature, and subsequently plays an essential role in
      biological functions.

PMID- 11298740
TI  - Structural analysis of the O-antigen polysaccharide from the Shiga toxin
      producing Escherichia coli O172.
AB  - The structure of the O-antigen polysaccharide from Escherichia coli O172 has been
      determined. In combination with sugar analysis, NMR spectroscopy shows that the
      polysaccharide is composed of pentasaccharide repeating units. Sequential
      information was obtained by mass spectrometry and two-dimensional NMR techniques.
      An O-acetyl group was present as 0.7 equivalent per repeating unit. Treatment of
      the O-deacetylated polysaccharide with aqueous 48% hydrofluoric acid rendered
      cleavage of the phosphodiester in the backbone of the polymer and the
      pentasaccharide isolated after gel permeation chromatography was structurally
      characterized. Subsequent NMR experiments on polymeric materials revealed the
      structure of the repeating unit of the O-polysaccharide from E. coli O172 as:-->P
      4)-alpha-D-Glcp-(1-->3)-alpha-L-FucpNAc-(1-->3)-alpha-D- GlcpNAc-(1-->3)-alpha-L
      FucpNAc-(1-->4)-alpha-D-Glcp6Ac-(1-->

PMID- 11298739
TI  - Nucleotide sequence analysis of 5'-flanking region of salicylate hydroxylase
      gene, and identification and purification of a LysR-type regulator, SalR.
AB  - The sal gene comprised of 1266 nucleotides encoding salicylate hydroxylase was
      cloned from the chromosomal DNA of Pseudomonas putida S-1 and sequenced [Suzuki,
      K., Mizuguchi, M., Ohnishi, K. and Itagaki, E. (1996) Biochim. Biophys. Acta
      1275, 154-156]. Here, we describe the nucleotide sequences of the regulatory
      region of the sal gene and an ORF (salR gene) divergently oriented from the sal
      gene, which encodes the protein SalR. This gene product positively controls sal
      gene expression at the transcriptional level. The salR gene consists of 930 base
      pairs starting from a GTG codon and encodes a protein of 309 amino acids with a
      molecular mass of 34 542 Da. The amino-acid sequence is homologous to LysR-family
      regulatory proteins such as CatR of P. putida RB1 and has helix-turn-helix DNA
      binding motif near its N-terminal. Transcription start sites of sal and salR
      genes were determined to lie 30- and 24-bp upstream of the respective initiation
      codons and separated from each other by 78 nucleotides. A Shine-Dalgarno sequence
      and the putative promoter sequences containing -10 and -35 sequences were seen in
      the sal and salR genes. Expression of the salR gene on a plasmid in Escherichia
      coli cells was confirmed by DNA mobility shift assay. For the overexpression of
      the salR gene, it was cloned to pET28a (pSAHR) which was transferred to E. coli
      BL21 (E. coli BL21/pSAHR), and expressed by an inducer, isopropyl thio-beta-D
      galactoside. SalR was further purified to homogeneity from the cell-free extracts
      in yields of approximately 3 mg.L-1 culture volume. The molecular mass was
      determined to be 33 kDa and the N-terminal amino-acid sequence was the same as
      that deduced from the nucleotide sequence of salR gene. Native SalR was also
      purified to homogeneity from P. putida S-1 with very low contents. The properties
      of the protein were similar to those of SalR expressed in E. coli.

PMID- 11298741
TI  - Purification, characterization and crystallization of thermostable anthranilate
      phosphoribosyltransferase from Sulfolobus solfataricus.
AB  - Anthranilate phosphoribosyltransferase (TrpD; EC 2.4.2.18) from the
      hyperthermophilic archaeon Sulfolobus solfataricus (ssTrpD) was expressed in
      Escherichia coli, purified and crystallized. Analytical gel permeation
      chromatography revealed a homodimeric composition of the enzyme. The steady-state
      kinetic characteristics suggest tight binding of the substrate anthranilic acid
      and efficient catalysis at the physiological growth temperature of S.
      solfataricus. Crystals of ssTrpD diffract to better than 2.6 A resolution and
      preliminary X-ray characterization was carried out. The crystals are suitable for
      structure determination.

PMID- 11298742
TI  - Structural consequences of site-directed mutagenesis in flexible protein domains:
      NMR characterization of the L(55,56)S mutant of RhoGDI.
AB  - The guanine dissociation inhibitor RhoGDI consists of a folded C-terminal domain
      and a highly flexible N-terminal region, both of which are essential for
      biological activity, that is, inhibition of GDP dissociation from Rho GTPases,
      and regulation of their partitioning between membrane and cytosol. It was shown
      previously that the double mutation L55S/L56S in the flexible region of RhoGDI
      drastically decreases its affinity for Rac1. In the present work we study the
      effect of this double mutation on the conformational and dynamic properties of
      RhoGDI, and describe the weak interaction of the mutant with Rac1 using chemical
      shift mapping. We show that the helical content of the region 45-56 of RhoGDI is
      greatly reduced upon mutation, thus increasing the entropic penalty for the
      immobilization of the helix, and contributing to the loss of binding. In contrast
      to wild-type RhoGDI, no interaction with Rac1 could be identified for amino-acid
      residues of the flexible domain of the mutant RhoGDI and only very weak binding
      was observed for the folded domain of the mutant. The origins of the effect of
      the L55S/L56S mutation on the binding constant (decreased by at least three
      orders of magnitude relative to wild-type) are discussed with particular
      reference to the flexibility of this part of the protein.

PMID- 11298743
TI  - Insight into thyrotropin receptor cleavage by engineering the single polypeptide
      chain luteinizing hormone receptor into a cleaving, two subunit receptor.
AB  - To gain insight into the thyrotropin hormone (TSH) receptor (TSHR) cleavage, we
      sought to convert the noncleaving luteinizing hormone (LH) receptor (LHR) into a
      cleaved, two-subunit molecule. For this purpose, we generated a series of LHR
      mutants and chimeric LH-TSH receptors. Cleavage of mature, ligand binding
      receptors on the cell surface was determined by covalent 125I-labeled hCG
      crosslinking to intact, stably transfected mammalian cells. We first targeted a
      cluster of three N-linked glycans in the LHR (N295, N303, N317) in a region
      corresponding to the primary TSHR cleavage site, which has only one N-linked
      glycan. Elimination by mutagenesis of the most strategic N-linked glycan (LHR
      N317Q) generated only a trace amount of LHR cleavage. Removal of the other N
      linked glycans had no additive effect. A much greater degree of cleavage (
      approximately 50%) was evident in a chimeric LH-TSHR in which the juxtamembrane
      segment of the LHR (domain E; amino acids 317-367) was replaced with the
      corresponding domain of the TSHR (residues 363-418). Similarly cleaving LHR were
      created using a much smaller component within this region, namely LHR-NET317-319
      replaced with TSHR-GQE367-369, or by substitution of the same three amino-acid
      residues with AAA (LHR-NET317-319AAA). In summary, our data alter current
      concepts regarding TSHR cleavage by suggesting limited (not absent) amino-acid
      specificity in a region important for TSHR cleavage (GQE367-369). The data also
      support the concept of a separate and distinct downstream cleavage site 2 in the
      TSHR.

PMID- 11298744
TI  - Carboxyl group of residue Asp647 as possible proton donor in catalytic reaction
      of alpha-glucosidase from Schizosaccharomyces pombe.
AB  - cDNA encoding Schizosaccharomyces pombe alpha-glucosidase was cloned from a
      library constructed from mRNA of the fission yeast, and expressed in
      Saccharomyces cerevisiae. The cDNA, 4176 bp in length, included a single ORF
      composed of 2910 bp encoding a polypeptide of 969 amino-acid residues with M(r)
      106 138. The deduced amino-acid sequence showed a high homology to those of alpha
      glucosidases from molds, plants and mammals. Therefore, the enzyme was
      categorized into the alpha-glucosidase family II. By site-directed mutagenesis,
      Asp481, Glu484 and Asp647 residues were confirmed to be essential in the
      catalytic reaction. The carboxyl group (-COOH) of the Asp647 residue was for the
      first time shown to be the most likely proton donor acting as the acid catalyst
      in the alpha-glucosidase of family II. Studies with the chemical modifier
      conduritol B epoxide suggested that the carboxylate group (-COO-) of the Asp481
      residue was the catalytic nucleophile, although the role of the Glu484 residue
      remains obscure.

PMID- 11298745
TI  - Hsp90 chaperone complexes are required for the activity and stability of yeast
      protein kinases Mik1, Wee1 and Swe1.
AB  - The Wee1 protein kinase negatively regulates entry into mitosis by mediating the
      inhibitory tyrosine phosphorylation of Cdc2-cyclin B kinase. The stability and
      activity of Wee1 from the fission yeast Schizosaccharomyces pombe is critically
      dependent on functional Hsp90 chaperones. Here we identify two related tyrosine
      protein kinases, Mik1 from fission yeast and its Saccharomyces cerevisiae homolog
      Swe1, as Hsp90 substrates and show that the kinase domain is sufficient to
      mediate this interaction. Morphological and biochemical defects arising from
      overexpression of the kinases in fission yeast are suppressed in the conditional
      Hsp90 mutant swo1-26. A subset of all three kinases is associated with the Hsp90
      cochaperones cyclophilin 40 and p23. Under conditions of impaired chaperone
      function or treatment with the Hsp90 inhibitory drug geldanamycin, intracellular
      levels of the kinases are reduced and the proteins become rapidly degraded by the
      proteasome machinery, indicating that Wee1, Mik1 and Swe1 require Hsp90
      heterocomplexes for their stability and maintenance of function.

PMID- 11298746
TI  - Endoplasmic reticulum proteins involved in glycosylphosphatidylinositol-anchor
      attachment: photocrosslinking studies in a cell-free system.
AB  - Assembly of glycosylphosphatidylinositol (GPtdIns)-anchored proteins requires
      translocation of the nascent polypeptide chain across the endoplasmic reticulum
      (ER) membrane and replacement of the C-terminal signal sequence with a GPtdIns
      moiety. The anchoring reaction is carried out by an ER enzyme, GPtdIns
      transamidase. Genetic studies with yeast indicate that the transamidase consists
      of a dynamic complex of at least two subunits, Gaa1p and Gpi8p. To study the
      GPtdIns-anchoring reaction, we used a small reporter protein that becomes GPtdIns
      anchored when the corresponding mRNA is translated in the presence of microsomes,
      in conjunction with site-specific photocrosslinking to identify ER membrane
      components that are proximal to the reporter during its conversion to a GPtdIns
      anchored protein. We generated variants of the reporter protein such that upon in
      vitro translation in the presence of Nepsilon-(5-azido-2-nitrobenzoyl)-lysyl
      tRNA, photoreactive lysine residues would be incorporated in the protein
      specifically near the GPtdIns-attachment site. We analyzed photoadducts resulting
      from UV irradiation of the samples. We show that proproteins can be crosslinked
      to the transamidase subunit Gpi8p, as well as to ER proteins of molecular mass
      approximately 60 kDa, approximately 70 kDa, and approximately 120 kDa. The
      identification of a photoadduct between a proprotein and Gpi8p provides the first
      direct evidence of an interaction between a proprotein substrate and one of the
      genetically identified transamidase subunits. The approximately 70-kDa protein
      that we identified may correspond to the other subunit Gaa1p, while the other
      proteins possibly represent additional, hitherto unidentified subunits of the
      mammalian GPtdIns transamidase complex.

PMID- 11298747
TI  - Assignment of the disulfide bonds of huwentoxin-II by Edman degradation
      sequencing and stepwise thiol modification.
AB  - A novel strategy combining Edman degradation and thiol modification was developed
      to assign the three disulfides of huwentoxin-II (HWTX-II), an insecticidal
      peptide purified from the venom of the spider Selenocosmia huwena.
      Phenylthiohydantoin (Pth) derivatives of Cys and the elimination product,
      dehydroalanine (DeltaSer), can be observed in the Cys cycles during Edman
      degradation of native HWTX-II. The appearance of two products indicates that the
      disulfides of HWTX-II were split and that the free thiol group of the second half
      cystine has been generated. Information about the nature of the disulfide bridges
      of HWTX-II could be obtained from the sequencing signal if the nascent thiols
      were modified stepwise by 4-vinylpyridine. Using this method the disulfide
      bridges of HWTX-II were assigned as Cys4-Cys18, Cys8-Cys29 and Cys23-Cys34, which
      is different from that seen in HWTX-I, a neurotoxic peptide from the same spider.
      Using this strategy, one can assign the disulfide bonds of small proteins by
      sequencing and modification n - 1 times, where n is the number of disulfide bonds
      in the protein. The above assignment of the disulfide bonds of HWTX-II was
      confirmed by MALDI-TOF MS of tryptic fragments of HWTX-II. Some disulfide
      interchanging during proteolysis was observed by monitoring the kinetics of
      proteolysis of HWTX-II by MALDI-TOF MS.

PMID- 11298748
TI  - Growth factor-stimulated protein synthesis is inhibited by sodium orthovanadate.
AB  - The study of intracellular signaling pathways has been aided by the use of sodium
      orthovanadate, a cell-permeable inhibitor of tyrosine phosphatases. However, long
      term addition of sodium orthovanadate is often cytotoxic. In this study we
      demonstrate that the growth factor-mediated increase in the rate of protein
      synthesis was inhibited by sodium orthovanadate. This effect of sodium
      orthovanadate was dose-dependent, with an IC50 of 40 microM and maximal
      inhibition obtained at 100 microM. As a consequence, the fetal bovine serum
      mediated induction of the immediate-early genes, c-Fos and MKP-1, at the protein
      level was inhibited by orthovanadate. Orthovanadate's ability to attenuate
      protein synthesis was partially reversible, and was no longer evident when the
      agent was added 6 h after addition of growth factor to cells. Analysis of several
      elements of signaling pathways which are known to regulate protein synthesis in a
      positive manner (p42/p44 MAPK, AKT and p70 S6K stimulation, and
      hyperphosphorylation of PHAS-I) were not inhibited but rather were stimulated by
      orthovanadate. Thus, sodium orthovanadate is a potent inhibitor of growth factor
      stimulated protein synthesis independent of p42/p44 MAPK or PI3K-p70 S6K
      activation.

PMID- 11298749
TI  - Varying competence for protein import into chloroplasts during the cell cycle in
      Chlamydomonas.
AB  - By studying the import of radioactively labelled small subunit of ribulose-1,5
      bisphosphate carboxylase (pSS) into chloroplasts of the green alga C. reinhardtii
      cw-15 protein delivery to chloroplasts was found to vary during the cell cycle.
      Chloroplasts were isolated from highly synchronous cultures at different time
      points during the cell cycle. When pSS was imported into 'young' chloroplasts
      isolated early in the light period about three times less pSS was processed to
      small subunit SS than in 'mature' chloroplasts from the middle of the light
      period. In 'young' chloroplasts also, less pSS was bound to the envelope surface.
      During the second half of the light period the import competence of isolated
      chloroplasts decreased again when based on chlorophyll content or cell volume,
      but did not change significantly when related to chloroplast number. Measurements
      of pSS binding to the surface of chloroplasts of different age indicated that the
      adaptation of protein import competence during the cell cycle is due to a
      variation of the number of binding sites per chloroplast surface area, rather
      than to modulation of the binding constant.

PMID- 11298750
TI  - Low and high density lipoprotein metabolism in primary cultures of hepatic cells
      from normal and apolipoprotein E knockout mice.
AB  - Apolipoprotein E (apoE) plays a major role in lipoprotein metabolism by mediating
      the binding of apoE-containing lipoproteins to receptors. The role of hepatic
      apoE in the catabolism of apoE-free lipoproteins such as low density lipoprotein
      (LDL) and high density lipoprotein-3 (HDL(3)) is however, unclear. We analyzed
      the importance of hepatic apoE by comparing human LDL and HDL(3) metabolism in
      primary cultures of hepatic cells from control C57BL/6J and apoE knockout (KO)
      mice. Binding analysis showed that the maximal binding capacity (Bmax) of LDL,
      but not of HDL(3), is increased by twofold in the absence of apoE
      synthesis/secretion. Compared to control hepatic cells, LDL and HDL(3)
      holoparticle uptake by apoE KO hepatic cells, as monitored by protein
      degradation, is reduced by 54 and 77%, respectively. Cleavage of heparan sulfate
      proteoglycans (HSPG) by treatment with heparinase I reduces LDL association by
      21% in control hepatic cells. Thus, HSPG alone or a hepatic apoE-HSPG complex is
      partially involved in LDL association with mouse hepatic cells. In apoE KO, but
      not in normal hepatic cells, the same treatment increases LDL uptake/degradation
      by 2.4-fold suggesting that in normal hepatic cells, hepatic apoE increases LDL
      degradation by masking apoB-100 binding sites on proteoglycans. Cholesteryl ester
      (CE) association and CE selective uptake (CE/protein association ratio) from LDL
      and HDL(3) by mouse hepatic cells were not affected by the absence of apoE
      expression. We also show that 69 and 72% of LDL-CE hydrolysis in control and apoE
      KO hepatic cells, respectively, is sensitive to chloroquine revealing the
      importance of a pathway linked to lysosomes. In contrast, HDL(3)-CE hydrolysis is
      only mediated by a nonlysosomal pathway in both control and apoE KO hepatic
      cells. Overall, our results indicate that hepatic apoE increases the holoparticle
      uptake pathway of LDL and HDL(3) by mouse hepatic cells, that HSPG devoid of apoE
      favors LDL binding/association but impairs LDL uptake/degradation and that apoE
      plays no significant role in CE selective uptake from either human LDL or HDL(3)
      lipoproteins.

PMID- 11298751
TI  - Specific inhibition of transforming growth factor-beta2 expression in human
      osteoblast cells by antisense phosphorothioate oligonucleotides.
AB  - To elucidate the role of endogenous transforming growth factor (TGF)-beta2 on
      human osteoblast cell, antisense phosphorothioate oligonucleotides (S-ODNs)
      complementary to regions in mRNA of TGF-beta2 were synthesized and examined their
      effects on TGF-beta2 production and cell proliferation in a human osteoblast cell
      line ROS 17/2. Antisense S-ODNs were designated for three different target
      regions in the mRNA of TGF-beta2. Among several antisense S-ODN analyzed, an
      oligonucleotide (AS-11) complementary to the translation initiation site of mRNA
      of TGF-beta2 demonstrated a selective and strong inhibitory effect on TGF-beta2
      production in osteoblast cells. Other antisense S-ODNs which were designated for
      other regions in mRNA of TGF-beta2 and one- or three-base mismatched analogs of
      AS-11 showed little or much less antisense activities than AS-11. Therefore, the
      most effective target site in mRNA of TGF-beta2 is at the initiation codon
      region. The antisense effects of AS-11 were observed without reduction of levels
      of mRNA of TGF-beta2. Furthermore, the inhibition of TGF-beta2 expression by
      antisense S-ODN appeared to enhance cell proliferation, demonstrating the growth
      inhibitory effect of autocrine TGF-beta2 in osteoblast cells.

PMID- 11298752
TI  - Oxidized adrenodoxin acts as a competitive inhibitor of cytochrome P450scc in
      mitochondria from the human placenta.
AB  - The conversion of cholesterol to pregnenolone by cytochrome P450scc is the rate
      determining step in placental progesterone synthesis. The limiting component for
      placental cytochrome P450scc activity is the concentration of adrenodoxin
      reductase in the mitochondria, where it permits cytochrome P450scc to work at
      only 16% of maximum velocity. Adrenodoxin reductase serves to reduce adrenodoxin
      as part of the electron transfer from NADPH to cytochrome P450scc. We therefore
      measured the proportion of adrenodoxin in the reduced form in intact mitochondria
      from the human placenta during active pregnenolone synthesis, using EPR. We found
      that the adrenodoxin pool was only 30% reduced, indicating that the adrenodoxin
      reductase concentration was insufficient to maintain the adrenodoxin in the fully
      reduced state. As both oxidized and reduced adrenodoxin can bind to cytochrome
      P450scc we tested the ability of oxidized adrenodoxin to act as a competitive
      inhibitor of pregnenolone synthesis. This was done in a fully reconstituted
      system comprising 0.3% Tween 20 and purified proteins, and in a partially
      reconstituted system comprising submitochondrial particles, purified adrenodoxin
      and adrenodoxin reductase. We found that oxidized adrenodoxin is an effective
      competitive inhibitor of placental cytochrome P450scc with a Ki value half that
      of the Km for reduced adrenodoxin. We conclude that the limiting concentration of
      adrenodoxin reductase present in placental mitochondria has a two-fold effect on
      cytochrome P450scc activity. It limits the amount of reduced adrenodoxin that is
      available to donate electrons to cytochrome P450scc and the oxidized adrenodoxin
      that remains, competitively inhibits the cytochrome.

PMID- 11298753
TI  - A novel RNA polymerase binding site upstream of the galactose promoter in
      Escherichia coli exhibits promoter-like activity.
AB  - RNA polymerase is known to bind and utilize the overlapping promoters P1 and P2
      in Escherichia coli galactose operon. We have identified an additional specific
      site upstream of P2, where RNA polymerase binds in a heparin-resistant manner.
      Binding of polymerase to this site, termed P3, occurs simultaneous to its binding
      at P1/P2. We have located this P3 site by DNase I footprinting. A 63 base pair
      region centered around position - 100 with respect to galP1 is protected by
      polymerase. Interestingly, a Pribnow box TATAAT is present within this protected
      region (-103 to -108). We have shown that transcription occurs from P3 in vitro.
      Primer extension analysis provides direct evidence that P3 is transcribed in
      vivo. The start site of transcription has been mapped at -96 position relative to
      galP1. beta-galactosidase assays with different gal promoter constructs reveal
      that while P3 alone functions as a weak in vivo promoter, it has a synergistic
      effect on transcription from the gal operon, since deletion of P3 or specifically
      mutating its -10 region result in a substantial reduction in the gal promoter
      activity.

PMID- 11298754
TI  - A subfraction of the yeast endoplasmic reticulum associates with the plasma
      membrane and has a high capacity to synthesize lipids.
AB  - Large parts of the endoplasmic reticulum of the yeast, Saccharomyces cerevisiae,
      are located close to intracellular organelles, i.e. mitochondria and the plasma
      membrane, as shown by fluorescence and electron microscopy. Here we report the
      isolation and characterization of the subfraction of the endoplasmic reticulum
      that is closely associated with the plasma membrane. This plasma membrane
      associated membrane (PAM) is characterized by its high capacity to synthesize
      phosphatidylserine and phosphatidylinositol. As such, PAM is reminiscent of MAM,
      a mitochondria associated membrane fraction of the yeast [Gaigg, B., Simbeni, R.,
      Hrastnik, C., Paltauf, F. & Daum, G. (1995) Biochim. Biophys. Acta 1234, 214
      220], although the specific activity of phosphatidylserine synthase and
      phosphatidylinositol synthase in PAM exceeds several-fold the activity in MAM and
      also in the bulk endoplasmic reticulum. In addition, several enzymes involved in
      ergosterol biosynthesis, namely squalene synthase (Erg9p), squalene epoxidase
      (Erg1p) and steroldelta24-methyltransferase (Erg6p), are highly enriched in PAM.
      A possible role of PAM in the supply of lipids to the plasma membrane is
      discussed.

PMID- 11298755
TI  - A basic residue at position 36p of the propeptide is not essential for the
      correct folding and subsequent autocatalytic activation of prochymosin.
AB  - Position 36p in the propeptides of gastric aspartic proteinases is generally
      occupied by lysine or arginine. This has led to the conclusion that a basic
      residue at this position, which interacts with the active-site aspartates, is
      essential for folding and activation of the zymogen. Lamb prochymosin has been
      shown by cDNA cloning to possess glutamic acid at 36p. To investigate the effect
      of this natural mutation which appears to contradict the proposed role of this
      residue, calf and lamb prochymosins and their two reciprocal mutants, K36pE and
      E36pK, respectively, were expressed in Escherichia coli, refolded in vitro, and
      autoactivated at pH 2 and 4.7. All four zymogens could be activated to active
      chymosin and, at both pH values, the two proteins with Glu36p showed higher
      activation rates than the two Lys36p forms. Glu36p was also demonstrated in
      natural prochymosin isolated from the fourth stomach of lamb, as well as being
      encoded in the genomes of sheep, goat and mouflon, which belong to the subfamily
      Caprinae. A conserved basic residue at position 36p of prochymosin is thus not
      obligatory for its folding or autocatalytic activation. The apparently
      contradictory results for porcine pepsinogen A [Richter, C., Tanaka, T., Koseki,
      T. & Yada, R.Y. (1999) Eur. J. Biochem. 261, 746-752] can be reconciled with
      those for prochymosin. Lys/Arg36p is involved in stabilizing the propeptide
      enzyme interaction, along with residues nearer the N-terminus of the propeptide,
      the sequence of which varies between species. The relative contribution of
      residue 36p to stability differs between pepsinogen and prochymosin, being larger
      in the former.

PMID- 11298756
TI  - Identification and expression of the genes and purification and characterization
      of the gene products involved in reactivation of coenzyme B12-dependent glycerol
      dehydratase of Citrobacter freundii.
AB  - The coenzyme B12-dependent glycerol dehydratase of Citrobacter freundii is
      subject to suicide inactivation by the natural substrate glycerol during
      catalysis. We identified dhaF and dhaG as the genes responsible for reactivation
      of inactivated dehydratase. Northern blot analyses revealed that both genes were
      expressed during glycerol fermentation. The dhaF gene is transcribed together
      with the three structural genes coding for glycerol dehydratase (dhaBCE), whereas
      dhaG is coexpressed with the dhaT gene encoding 1,3-propanediol dehydrogenase.
      The dhaF and dhaG gene products were copurified to homogeneity from cell-free
      extracts of a recombinant E. coli strain producing both His6-tagged proteins.
      Both proteins formed a tight complex with an apparent molecular mass of 150 000
      Da. The subunit structure of the native complex is probably alpha2beta2. The
      factor rapidly reactivated glycerol- or O2-inactivated hologlycerol dehydratase
      and activated the enzyme-cyanocobalamin complex in the presence of coenzyme B12,
      ATP, and Mg2+. The DhaF-DhaG complex and DhaF exhibited ATP-hydrolyzing activity,
      which was not directly linked to the reactivation of dehydratase. The purified
      DhaF-DhaG complex of C. freundii efficiently cross-activated the enzyme
      cyanocobalamin complex and the glycerol-inactivated glycerol dehydratase of
      Klebsiella pneumoniae. It was not effective with respect to the glycerol
      dehydratase of Clostridium pasteurianum and to diol dehydratases of enteric
      bacteria.

PMID- 11298757
TI  - Solution structure of the main alpha-amylase inhibitor from amaranth seeds.
AB  - The most abundant alpha-amylase inhibitor (AAI) present in the seeds of
      Amaranthus hypochondriacus, a variety of the Mexican crop plant amaranth, is the
      smallest polypeptide (32 residues) known to inhibit alpha-amylase activity of
      insect larvae while leaving that of mammals unaffected. In solution, 1H NMR
      reveals that AAI isolated from amaranth seeds adopts a major trans (70%) and
      minor cis (30%) conformation, resulting from slow cis-trans isomerization of the
      Val15-Pro16 peptide bond. Both solution structures have been determined using 2D
      1H-NMR spectroscopy and XPLOR followed by restrained energy refinement in the
      consistent-valence force field. For the major isomer, a total of 563 distance
      restraints, including 55 medium-range and 173 long-range ones, were available
      from the NOESY spectra. This rather large number of constraints from a protein of
      such a small size results from a compact fold, imposed through three disulfide
      bridges arranged in a cysteine-knot motif. The structure of the minor cis isomer
      has also been determined using a smaller constraint set. It reveals a different
      backbone conformation in the Pro10-Pro20 segment, while preserving the overall
      global fold. The energy-refined ensemble of the major isomer, consisting of 20
      low-energy conformers with an average backbone rmsd of 0.29 +/- 0.19 A and no
      violations larger than 0.4 A, represents a considerable improvement in precision
      over a previously reported and independently performed calculation on AAI
      obtained through solid-phase synthesis, which was determined with only half the
      number of medium-range and long-range restraints reported here, and featured the
      trans isomer only. The resulting differences in ensemble precision have been
      quantified locally and globally, indicating that, for regions of the backbone and
      a good fraction of the side chains, the conformation is better defined in the new
      solution structure. Structural comparison of the solution structure with the X
      ray structure of the inhibitor when bound to its alpha-amylase target in Tenebrio
      molitor shows that the backbone conformation is only slightly adjusted on
      complexation, while that of the side chains involved in protein-protein contacts
      is similar to those present in solution. Therefore, the overall conformation of
      AAI appears to be predisposed to binding to its target alpha-amylase, confirming
      the view that it acts as a lid on top of the alpha-amylase active site.

PMID- 11298758
TI  - Novel activator protein-2alpha splice-variants function as transactivators of the
      ovine placental lactogen gene.
AB  - Activator protein-2 (AP-2) has been implicated as a transactivator of the human
      and ovine placental lactogen (oPL) genes. Transcriptional enhancement through an
      AP-2 cis-acting element has been described for other genes expressed in the
      placenta, but the AP-2 isoform enhancing expression is species dependent.
      Transactivation of the oPL minimal promoter (-124 bp to +16 bp) by AP-2 was
      confirmed by mutational analysis in transiently transfected human choriocarcinoma
      cells (BeWo). AP-2alpha was localized in ovine chorionic epithelial cells by
      immunohistochemistry and a 3-kb transcript was identified by Northern
      hybridization. Four nearly full-length AP-2 cDNAs were isolated from an ovine
      placenta cDNA library. Nucleotide sequencing these cDNAs revealed that the AP-2
      mRNA expressed in the ovine placenta shares identity with human AP-2alpha, but
      variations in the predicted N-terminus were observed, and three unique AP-2alpha
      splice-variants were identified. Expression of AP-2alpha variants in HepG2 cells,
      devoid of endogenous AP-2, indicates that enhancement through the AP-2 element in
      the oPL gene minimal promoter was variant dependent. RNA transcripts for all of
      the ovine AP-2alpha splice-variants were confirmed in ovine placenta by RT-PCR,
      and homologs for two variants were found in human placenta. However, only one AP
      2alpha transcript, which shares identity to Xenopus AP-2alpha, was expressed in
      BeWo cells. Immunoblot analysis confirmed AP-2alpha variants in ovine chorionic
      binucleate cell nuclear extracts, one of which migrates similar to the AP-2alpha
      variant identified in BeWo cell nuclear extracts. These data indicate the
      presence of new mammalian AP-2alpha splice-variants that augment transactivation
      of the oPL gene in ovine chorionic binucleate cells.

PMID- 11298759
TI  - Phosphorylation and oligomerization states of native pig brain HSP90 studied by
      mass spectrometry.
AB  - HSP90 is one of the most abundant proteins in the cytosol of eukaryotic cells.
      HSP90 forms transient or stable complexes with several key proteins involved in
      signal transduction including protooncogenic protein kinases and nuclear
      receptors, it interacts with cellular structural elements such as actin
      microfilament, tubulin-microtubule and intermediate filaments, and also exhibits
      conventional chaperone functions. This protein exists in two isoforms alpha-HSP90
      and beta-HSP90, and it forms dimers which are crucial species for its biological
      activity. PAGE, ESI-MS and MALDI-MS were used to study HSP90 purified from pig
      brain. The two protein isoforms were clearly distinguished by ESI-MS, the alpha
      isoform being approximately six times more abundant than the beta isoform. ESI-MS
      in combination with lambda phosphatase treatment provided direct evidence of the
      existence of four phosphorylated forms of native pig brain alpha-HSP90, with the
      diphosphorylated form being the most abundant. For the beta isoform, the di
      phosphorylated was also the most abundant. MALDI mass spectra of HSP90 samples
      after chemical cross-linking showed a high percentage of alpha-alpha homodimers.
      In addition, evidence for the existence of higher HSP90 oligomers was obtained.

PMID- 11298760
TI  - Identification of catalytically important residues in the active site of
      Escherichia coli transaldolase.
AB  - The roles of invariant residues at the active site of transaldolase B from
      Escherichia coli have been probed by site-directed mutagenesis. The mutant
      enzymes D17A, N35A, E96A, T156A, and S176A were purified from a talB-deficient
      host and analyzed with respect to their 3D structure and kinetic behavior. X-ray
      analysis showed that side chain replacement did not induce unanticipated
      structural changes in the mutant enzymes. Three mutations, N35A, E96A, and T156A
      resulted mainly in an effect on apparent kcat, with little changes in apparent Km
      values for the substrates. Residues N35 and T156 are involved in the positioning
      of a catalytic water molecule at the active site and the side chain of E96
      participates in concert with this water molecule in proton transfer during
      catalysis. Substitution of Ser176 by alanine resulted in a mutant enzyme with
      2.5% residual activity. The apparent Km value for the donor substrate, fructose 6
      phosphate, was increased nearly fivefold while the apparent Km value for the
      acceptor substrate, erythrose 4-phosphate remained unchanged, consistent with a
      function for S176 in the binding of the C1 hydroxyl group of the donor substrate.
      The mutant D17A showed a 300-fold decrease in kcat, and a fivefold increase in
      the apparent Km value for the acceptor substrate erythrose 4-phosphate,
      suggesting a role of this residue in carbon-carbon bond cleavage and
      stabilization of the carbanion/enamine intermediate.

PMID- 11298761
TI  - P-Glycoprotein conformational changes detected by antibody competition.
AB  - Conformational changes accompanying P-glycoprotein (Pgp) mediated drug transport
      are reflected by changes in the avidity of certain monoclonal antibodies (mAbs).
      More of the UIC2 mAb binds to Pgp-expressing cells in the presence of substrates
      or modulators [Mechetner, E.B., Schott, B., Morse, S.B., Stein, W., Druley, T.,
      Dvis, K.A., Tsuruo, T. & Roninson, I.B. (1997) Proc. Natl Acad. Sci. USA 94,
      12908-12913], while the binding of other mAbs (e.g. MM12.10, MRK16, 4E3) is not
      conformation sensitive. Pre-staining of Pgp+ cells with UIC2 decreased the
      subsequent binding of MM12.10 mAb by about 30-40%, suggesting that there are Pgp
      molecules available for both UIC2 and MM12.10, and others accessible only for
      MM12.10. In the presence of certain substrates/modulators such as vinblastin,
      cyclosporin A or valinomycin, the MM12.10 reactivity was completely abolished by
      preincubation with UIC2. However, verapamil, Tween-80 and nifedipine did not
      influence the ratio of bound mAbs significantly. This is the first assay to our
      knowledge, sharply distinguishing two classes of modulators. The conformational
      changes accompanying the mAb competition phenomenon appear to be closely related,
      though not identical to those accompanying the UIC2-shift, as suggested by the
      simultaneous assessment of the two phenomena.

PMID- 11298762
TI  - GroEL-assisted refolding of adrenodoxin during chemical cluster insertion.
AB  - Chemical reconstitution of recombinant bovine adrenal mitochondrial
      apoadrenodoxin was carried out in the presence of the nonhomologous chaperone
      protein GroEL and of the cochaperone GroES, both in the presence and in the
      absence of ATP. The approach used here was different from the one characterizing
      studies on chaperone activity, as we used an adrenodoxin apoprotein, devoid of
      the cluster iron and sulfide, rather than a denaturant-unfolded form of the
      protein, and catalytic amounts of the chaperone proteins. A possible scaffolding
      role for two bacterial sulfur transferases, namely, rhodanese from Azotobacter
      vinelandii and a rhodanese-like sulfurtransferase from Escherichia coli, was also
      investigated in the absence of the enzyme substrates. The extent and the rate of
      adrenodoxin refolding following cluster insertion was measured by spectroscopy
      and by monitoring the activity recovery in a NADPH-cytochrome c reduction assay.
      These measurements were carried out on the unresolved reaction mixture and on the
      adrenodoxin-containing fraction obtained by HPLC fractionation of the
      reconstitution mixture at different reaction times. The rate and extent of
      cluster insertion and activity recovery were substantially improved by addition
      of GroEL and increased with increasing the GroEL/apoadrenodoxin ratio. GroES and
      ATP had no effect by themselves, and did not enhance the effect of GroEL. A.
      vinelandii rhodanese, the E. coli sulfurtransferase, and bovine serum albumin had
      no effect on the rate and yield of chemical reconstitution. The accelerated
      chemical reconstitution of apoadrenoxin in the presence of GroEL is therefore
      attributable to a scaffolding effect of this protein.

PMID- 11298763
TI  - Molecular cloning of a mammalian nuclear phosphoprotein NUCKS, which serves as a
      substrate for Cdk1 in vivo.
AB  - We have isolated and characterized a cDNA encoding a mammalian nuclear
      phosphoprotein NUCKS, previously designated P1. Molecular analyses of several
      overlapping and full-length cDNAs from HeLa cells and rat brain revealed a
      protein with an apparent molecular mass of 27 kDa in both species. The deduced
      amino-acid sequences are highly conserved between human and rodents, but show no
      homology with primary structures in protein databases or with translated
      sequences of cDNAs in cDNA databanks. Although the protein has some features in
      common with the high mobility group proteins HMGI/Y, attempts to find a putative
      protein family by database query using both sequence alignment methods and amino
      acid composition have failed. Northern blot analyses revealed that human and rat
      tissues contain three NUCKS transcripts varying in size from 1.5 to 6.5 kb. All
      human and rat tissues express the gene, but the level of transcripts varies among
      different tissues. Circular dichroism analysis and secondary structure
      predictions based on the amino-acid sequence indicate a low level of alpha
      helical content and substantial amounts of beta turn structures. The protein is
      phosphorylated in all phases of the cell cycle and exhibits mitosis-specific
      phosphorylation of threonine residues. Phosphopeptide mapping and back
      phosphorylation experiments employing NUCKS from HeLa interphase and metaphase
      cells show that the protein is phosphorylated by Cdk1 during mitosis of the cell
      cycle.

PMID- 11298764
TI  - Application of MALDI-TOF MS to lysine-producing Corynebacterium glutamicum: a
      novel approach for metabolic flux analysis.
AB  - In the present work, a novel comprehensive approach of (13)C-tracer studies with
      labeling measurements by MALDI-TOF MS, and metabolite balancing was developed to
      elucidate key fluxes in the central metabolism of lysine producing
      Corynebacterium glutamicum during batch culture. MALDI-TOF MS methods established
      allow the direct quantification of labeling patterns of low molecular mass
      Corynebacterium products from 1 microL of diluted culture supernatant. A
      mathematical model of the central Corynebacterium metabolism was developed, that
      describes the carbon transfer through the network via matrix calculations in a
      generally applicable way and calculates steady state mass isotopomer
      distributions of the involved metabolites. The model was applied for both
      experimental planning of tracer experiments and parameter estimation. Metabolic
      fluxes were calculated from stoichiometric data and from selected mass intensity
      ratios of lysine, alanine, and trehalose measured by MALDI-TOF MS in tracer
      experiments either with 1-(13)C glucose or with mixtures of (13)C6/(12)C6
      glucose. During the phase of maximum lysine production C. glutamicum ATCC 21253
      exhibited high relative fluxes into the pentose phosphate pathway of 71%, a
      highly reversible glucose-6-phosphate isomerase, significant backfluxes from the
      tricarboxylic acid cycle to the pyruvate node consuming the lysine precursor
      oxaloacetate, 36% net flux of anaplerotic carboxylation and 63% contribution of
      the dehydrogenase branch in the lysine biosynthetic pathway. Due to the
      straightforward and simple measurements of selected labeling patterns by MALDI
      TOF MS sensitively reflecting the flux parameters of interest, the presented
      approach has an excellent potential to extend metabolic flux analysis from single
      experiments with enormous experimental effort to a broadly applied technique.

PMID- 11298765
TI  - Influence of cyclodextrin ring substituents on folding-related aggregation of
      bovine carbonic anhydrase.
AB  - A common obstacle to proper renaturation of an unfolded protein is aggregation,
      an intermolecular side reaction of immense importance in biotechnology and in the
      pathogenesis of several neurodegenerative diseases. Cyclic sugars known as
      cyclodextrins have been used as protein-folding aids. The effect of cyclodextrin
      chemistry on aggregation and refolding of carbonic anhydrase was evaluated in
      this study. Size-exclusion HPLC showed that cyclodextrins inhibit aggregate
      formation without interfering with the correct renaturation of carbonic
      anhydrase. PAGE of refolded enzyme provides further evidence of inhibition of
      folding-related aggregation by natural and chemically modified cyclodextrins.
      Although the amount of aggregate formed and recovery of active enzyme was
      dependent on cavity size, the nature of the chemical substituents found on the
      rims of the sugar molecule seems to play a more important role in cyclodextrin
      assisted refolding of carbonic anhydrase. In general, neutral or cationic
      cyclodextrins with small cavities were found to be better folding aids than
      anionic cyclodextrins with larger holes. Although the exact prediction of the
      effect of a cyclodextrin substitution on protein refolding is not possible at
      present, these results clearly show that modified cyclodextrins can be designed
      that effectively inhibit protein aggregation.

PMID- 11298766
TI  - Central carbon metabolism of Saccharomyces cerevisiae explored by biosynthetic
      fractional (13)C labeling of common amino acids.
AB  - Aerobic and anaerobic central metabolism of Saccharomyces cerevisiae cells was
      explored in batch cultures on a minimal medium containing glucose as the sole
      carbon source, using biosynthetic fractional (13)C labeling of proteinogenic
      amino acids. This allowed, firstly, unravelling of the network of active central
      pathways in cytosol and mitochondria, secondly, determination of flux ratios
      characterizing glycolysis, pentose phosphate cycle, tricarboxylic acid cycle and
      C1-metabolism, and thirdly, assessment of intercompartmental transport fluxes of
      pyruvate, acetyl-CoA, oxaloacetate and glycine. The data also revealed that
      alanine aminotransferase is located in the mitochondria, and that amino acids are
      synthesized according to documented pathways. In both the aerobic and the
      anaerobic regime: (a) the mitochondrial glycine cleavage pathway is active, and
      efflux of glycine into the cytosol is observed; (b) the pentose phosphate
      pathways serve for biosynthesis only, i.e. phosphoenolpyruvate is entirely
      generated via glycolysis; (c) the majority of the cytosolic oxaloacetate is
      synthesized via anaplerotic carboxylation of pyruvate; (d) the malic enzyme plays
      a key role for mitochondrial pyruvate metabolism; (e) the transfer of
      oxaloacetate from the cytosol to the mitochondria is largely unidirectional, and
      the activity of the malate-aspartate shuttle and the succinate-fumarate carrier
      is low; (e) a large fraction of the mitochondrial pyruvate is imported from the
      cytosol; and (f) the glyoxylate cycle is inactive. In the aerobic regime, 75% of
      mitochondrial oxaloacetate arises from anaplerotic carboxylation of pyruvate,
      while in the anaerobic regime, the tricarboxylic acid cycle is operating in a
      branched fashion to fulfill biosynthetic demands only. The present study shows
      that fractional (13)C labeling of amino acids represents a powerful approach to
      study compartmented eukaryotic systems.

PMID- 11298767
TI  - Molecular characterization of an anti-epilepsy peptide from the scorpion Buthus
      martensi Karsch.
AB  - For a long time Asian scorpion Buthus martensi Karsch (BmK) has been used in
      Chinese traditional medicine to cure many diseases of nervous system. Here we
      report the purification and characterization of a pharmacologically active
      neurotoxin from the scorpion BmK. This toxin had little toxicity in mice and
      insects but was found to have an anti-epilepsy effect in rats, and is thus named
      as BmK anti-epilepsy peptide (BmK AEP). Its amino-acid sequence was determined by
      lysylendopeptidase digestion, Edman degradation and mass spectrographic analysis.
      Based on the determined sequence, the gene coding for this peptide was also
      cloned and sequenced by the 3' and 5' RACE methods. It encodes a precursor of 85
      amino-acid residues including a signal peptide of 21 residues, a mature peptide
      of 61 residues and three additional residues Gly-Lys-Lys at the C-terminus. The
      additional Gly sometimes followed by one or two basic residues is prerequisite
      for the amidation of its C-terminus. C-terminal amidation was also verified by
      the molecular-mass determination of BmK AEP. This anti-epilepsy peptide toxin
      shares homology with other depressant insect toxins. The remarkable difference
      between them was mainly focused at residues 6, 7 and 39; these residues might
      relate to the unique action of BmK AEP.

PMID- 11298768
TI  - Regulation of expression of terminal oxidases in Paracoccus denitrificans.
AB  - In order to study the induction of terminal oxidases in Paracoccus denitrificans,
      their promoters were fused to the lacZ reporter gene and analysed in the wild
      type strain, in an FnrP-negative mutant, in a cytochrome bc1-negative mutant, and
      in six single or double oxidase-negative mutant strains. The strains were grown
      under aerobic, semi-aerobic, and denitrifying conditions. The oxygen-sensing
      transcriptional-regulatory protein FnrP negatively regulated the activity of the
      qox promoter, which controls expression of the ba3-type quinol oxidase, while it
      positively regulated the activity of the cco promoter, which controls expression
      of the cbb3-type cytochrome c oxidase. The ctaDII and ctaC promoters, which
      control the expression of the aa3-type cytochrome c oxidase subunits I and II,
      respectively, were not regulated by FnrP. The activities of the latter two
      promoters, however, did decrease with decreasing oxygen concentrations in the
      growth medium, suggesting that an additional oxygen-sensing mechanism exists that
      regulates transcription of ctaDII and ctaC. Apparently, the intracellular oxygen
      concentration (as sensed by FnrP) was not the only signal to which the oxidase
      promoters responded. At given extracellular oxygen status, both the qox and the
      cco promoters responded to mutations in terminal oxidase genes, whereas the
      ctaDII and ctaC promoters did not. The change of electron distribution through
      the respiratory network, resulting from elimination of one or more oxidase genes,
      may have changed intracellular signals that affect the activities of the qox and
      cco promoters. On the other hand, the re-routing of electron distribution in the
      respiratory mutants hardly affected the oxygen consumption rate as compared to
      that of the wild-type. This suggests that the mutants adapted their respiratory
      network in such a way that they were able to consume oxygen at a rate similar to
      that of the wild-type strain.

PMID- 11298769
TI  - Identification and characterization of the genes for N-acetylglucosamine kinase
      and N-acetylglucosamine-phosphate deacetylase in the pathogenic fungus Candida
      albicans.
AB  - Like bacteria and many fungi, the pathogenic fungus Candida albicans can utilize
      GlcNAc as a carbon source for growth. A cluster of six genes was identified in
      the C. albicans genome. One of the genes in the cluster was CaNAG1, which is
      responsible for GlcN6P deaminase and is therefore essential for GlcNAc-dependent
      growth. The other five genes were designated CaNAG2, CaNAG3, CaNAG4, CaNAG5 and
      CaNAG6. The mRNA levels of CaNAG1, CaNAG2 and CaNAG5 were significantly induced
      by GlcNAc, whereas those of CaNAG3, CaNAG4 and CaNAG6 were not. Neither CaNAG2
      nor CaNAG5 was essential for growth, but disruption of CaNAG2 or CaNAG5 greatly
      retarded the growth of cells using GlcNAc as the sole carbon source. Although no
      homolog of CaNAG2 or CaNAG5 was found in the Saccharomyces cerevisiae genome,
      CaNag2p displayed sequence similarities to Escherichia coli nagA, and CaNag5p is
      homologous to a wide variety of hexose kinases. When expressed as a fusion
      protein with glutathione S-transferase (GST), CaNag5p produced GlcNAc-P from
      GlcNAc in the presence of ATP, whereas GST alone did not. Furthermore, the
      recombinant GST-CaNag2p fusion protein converted GlcNAcP, which was produced by
      CaNag5p, into GlcNP. These results clearly demonstrate that CaNAG2 and CaNAG5
      encode GlcNAcP deacetylase and GlcNAc kinase, respectively. CaNag5p recognized
      glucose and mannose as substrates, whereas the recently identified human GlcNAc
      kinase was specific to GlcNAc. Deletion of CaNAG2 or CaNAG5 markedly, and that of
      CaNAG1 moderately, attenuated the virulence of C. albicans in a mouse systemic
      infection model. Thus, it appears that GlcNAc metabolism of C. albicans is
      closely associated with its virulence.

PMID- 11298770
TI  - Activation of the Sarcophaga lectin gene promoter by (A + T)-stretch binding
      protein.
AB  - Previously, we purified and isolated a cDNA for (A + T)-stretch binding protein
      (ATBP) that binds to (A + T)-stretches in the 5' upstream region of the
      Sarcophaga lectin gene [Nakanishi-Matsui, M., Kubo, T. & Natori, S. (1995) Eur.
      J. Biochem. 230, 396-400]. Here, we used a luciferase reporter to examine the
      effect of ATBP on transcription of the Sarcophaga lectin gene. Deletion
      experiments revealed that ATBP activates the Sarcophaga lectin gene in a 5'
      upstream sequence-dependent manner, and that at least the N-terminal 25 residues,
      the three Zn-finger domains, an acidic domain and the third hydrophobic domain of
      ATBP are indispensable for its function. Furthermore, a synergistic effect was
      detected between ATBP and Dif, suggesting that ATBP is involved in the activation
      of insect immunity genes.

PMID- 11298771
TI  - Multisite control of the Crabtree effect in ascites hepatoma cells.
AB  - AS-30D hepatoma cells, a highly oxidative and fast-growing tumor line, showed
      glucose-induced and fructose-induced inhibition of oxidative phosphorylation (the
      Crabtree effect) of 54% and 34%, respectively. To advance the understanding of
      the underlying mechanism of this process, the effect of 5 mM glucose or 10 mM
      fructose on the intracellular concentration of several metabolites was
      determined. The addition of glucose or fructose lowered intracellular Pi (40%),
      and ATP (53%) concentrations, and decreased cytosolic pH (from 7.2 to 6.8).
      Glucose and fructose increased the content of AMP (30%), glucose 6-phosphate,
      fructose 6-phosphate and fructose 1,6-bisphosphate (15, 13 and 50 times,
      respectively). The cytosolic concentrations of Ca2+ and Mg2+ were not modified.
      The addition of galactose or glycerol did not modify the concentrations of the
      metabolites. Mitochondria isolated from AS-30D cells, incubated in media with low
      Pi (0.6 mM) at pH 6.8, exhibited a 40% inhibition of oxidative phosphorylation.
      The data suggest that the Crabtree effect is the result of several small
      metabolic changes promoted by addition of exogenous glucose or fructose.

PMID- 11298772
TI  - Both the N- and C-terminal chaperone sites of Hsp90 participate in protein
      refolding.
AB  - Hsp90 is able to bind partially unfolded firefly luciferase and maintain it in a
      refoldable state; the subsequent successive action of the 20S proteasome
      activator PA28, Hsc70 and Hsp40 enables its refolding. Hsp90 possesses two
      chaperone sites in the N- and C-terminal domains that prevent the aggregation of
      denatured proteins. Here we show that both chaperone sites of Hsp90 are effective
      not only in capturing thermally denatured luciferase, but also in holding it in a
      state prerequisite for the successful refolding process mediated by PA28, Hsc70
      and Hsp40. In contrast, the heat-induced activity of Hsp90 to bind chemically
      denature dihydrofolate reductase efficiently and prevent its rapid spontaneous
      refolding was detected in the N-terminal site of Hsp90 only, while the C-terminal
      site was without effect. Thus it is most likely that both the N- and C-terminal
      chaperone sites may contribute to Hsp90 function as holder chaperones, however,
      in a significantly distinct manner.

PMID- 11298773
TI  - Heat shock proteins and atherosclerosis.

PMID- 11298774
TI  - Comparative study on antibodies to human and bacterial 60 kDa heat shock proteins
      in a large cohort of patients with coronary heart disease and healthy subjects.
AB  - BACKGROUND: Recent observations indicate an association between antibodies
      against mycobacterial heat shock protein (hsp65) and coronary heart disease
      (CHD). Previously, we reported on marked differences in antigen specificity and
      complement activating ability of anti-hsp65 antibodies and auto-antibodies
      against human heat shock protein, hsp60. Here, we investigated whether there are
      differences between antih-sp65 and anti-hsp60 antibodies in their association
      with CHD. DESIGN: We measured by ELISA the levels of antibodies to hsp65, hsp60
      and E. coli-derived GroEL in three groups: Group I, 357 patients with severe CHD
      who underwent by-pass surgery; Group II, 67 patients with negative coronary
      angiography; Group III, 321 healthy blood donors. Antibodies against Helicobacter
      pylori were also measured by commercial ELISA. RESULTS: As calculated by multiple
      regression analysis, the levels of anti-hsp60 auto-antibodies were significantly
      higher in Group I compared to Group II (P = 0.007) or Group III (P < 0.0001). By
      contrast, although concentrations of anti-hsp65 and anti-GroEL antibodies in
      Group I were higher than in Group III, no significant differences between Group I
      and Group II were found. Antibodies to the two bacterial hsp strongly correlated
      to each other, but either did not correlate or weakly correlated to hsp60. In
      Group I, serum concentrations of anti-H.pylori antibodies significantly
      correlated with those of anti-hsp65 and anti-GroEL antibodies but they did not
      correlate with the anti-hsp60 antibodies. CONCLUSIONS: As to their clinical
      relevance, a remarkable difference become evident between antibodies to human
      hsp60 and antibodies against bacterial hsp in the extent of association with CHD.
      On the basis of these findings and some pertinent literature data, an alternative
      explanation for the association between high level of anti-hsp antibodies and
      atherosclerotic vascular diseases is raised.

PMID- 11298775
TI  - Extrasystolic beats affect transmural electrical dispersion during programmed
      electrical stimulation.
AB  - BACKGROUND: Experimental studies suggest that the electrocardiographic Tpeak-Tend
      (TpTe) interval reflects transmural dispersion of repolarization (TDR). The
      genesis and role of the TpTe interval in a clinical setting have not been
      established. This study aimed to assess the clinical usefulness of the TpTe
      interval as an index of TDR and a pro-arrhythmic marker. MATERIALS AND METHODS:
      Endocardial monophasic action potential (MAP) duration and electrocardiographic
      QTp, QTe and TpTe intervals were assessed in 13 patients undergoing an
      electrophysiological study. Surface electrocardiograms were recorded during right
      ventricular pacing (Basic Cycle Length = 600 ms) before and after single
      extrastimuli. RESULTS: Ventricular arrhythmia was induced in six patients. During
      ventricular pacing, MAP duration and QTp intervals shortened in response to
      extrastimuli applied at progressively shorter coupling intervals. In contrast,
      QTe intervals increased in response to premature stimulation and QTe dispersion
      increased at short coupling intervals. During sinus rhythm, the TpTe interval was
      greater in the inducible group in leads V3-V4. Premature stimulation increased
      the duration of TpTe intervals, suggesting an increase in TDR. The maximum TpTe
      interval was greater in the inducible than in the noninducible group, both during
      baseline ventricular drive pacing (163 +/- 22 vs. 130 +/- 27 ms, respectively, P
      < 0.03) and after application of shortly coupled extrastimuli (263 +/- 66 vs. 200
      +/- 47 ms, respectively, P < 0.05). CONCLUSIONS: The TpTe interval of surface ECG
      is likely to represent TDR. TDR is increased by premature ventricular stimulation
      and the magnitude of the maximum TpTe interval (i.e. maximum TDR) during
      ventricular pacing is greater in patients with inducible arrhythmias.

PMID- 11298776
TI  - The hormone sensitive lipase gene in familial combined hyperlipidemia and insulin
      resistance.
AB  - BACKGROUND: Insulin resistance in the most common familial dyslipidemia, familial
      combined hyperlipidemia (FCHL), could be due to variations in the hormone
      sensitive lipase (HSL) gene. MATERIALS AND METHODS: The coding region of the HSL
      gene was screened with the single strand conformation polymorphism analysis in
      probands of 27 FCHL families with 228 members. In addition, the C-60G promoter
      substitution of the HSL gene was determined by the restriction fragment length
      polymorphism analysis in these subjects. RESULTS: No variants in the coding
      region of the HSL gene were found and the allele frequencies of the C-60G
      promoter substitution and the silent variant (G3138A) in the 3' untranslated
      region did not differ between 110 control subjects and 27 probands with FCHL.
      However, in control women the C-60G substitution was associated with high body
      mass index [30.6 +/- 0.9 kg m(-2) (mean +/- SD) in subjects with the C/G genotype
      and 24.8 +/- 4.6 in subjects with the C/C genotype, P = 0.012], and in control
      men with high rates of insulin-stimulated whole body glucose uptake (70.1 +/-
      14.7 vs. 56.7 +/- 14.2 micromol kg(-1) min(-1), P = 0.014). In 228 FCHL family
      members this substitution was associated with high low-density lipoprotein
      cholesterol levels in men (4.51 +/- 1.12 vs. 5.17 +/- 1.28 mmol L(-1), P =
      0.049), but not in women. CONCLUSIONS: The HSL gene is not a major gene for FCHL.
      However, the - 60G allele of this gene may affect body weight, insulin
      sensitivity and serum cholesterol levels.

PMID- 11298777
TI  - Large rearrangements of the LDL receptor gene and lipid profile in a FH Spanish
      population.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease
      caused by mutations in the low-density lipoprotein receptor (LDLR) gene. To date,
      there has not been a systematic survey of the frequency of gross mutations in the
      LDLR gene in the Spanish population. The objective of our study was to
      investigate large rearrangements in the Spanish FH population and the relation
      between the kind of large rearrangement and the phenotype in carrier families.
      MATERIALS AND METHODS: The LDLR gene was screened to detect major rearrangements
      in a sample of 89 probands. Southern blot, long polymerase chain reaction (PCR),
      reverse transcription (RT) -PCR and DNA sequencing were used to detect and
      characterize the mutations. RESULTS: Five large rearrangements were found in six
      probands. Two mutations were due to duplications of internal regions of the gene,
      whereas the rest were caused by partial deletions, which eliminated the promoter
      region in two cases. The internal rearrangements, two duplications and one
      deletion, were apparently caused by recombination between ALU sequences and the
      study of their mRNA indicated that the reading frame was maintained. The analysis
      of the lipid profile between patients with similar characteristics (age, sex,
      body mass index, etc.) but carrying mutations that either eliminated the promoter
      region or produced internal rearrangements showed significant differences (total
      cholesterol: 366.6 +/- 81.8 vs. 304.6 +/- 25.1 P = 0.023, and LDL cholesterol:
      317.7 +/- 65.1 vs. 249.2 +/- 27.4 P = 0.003). CONCLUSIONS: The frequency of large
      mutations in a Spanish FH sample was close to 7% and at least four of the
      mutations found had not been described in other populations. Mutations that
      eliminate the promoter region originate more severe hypercholesterolemia than
      defective mutations, which suggests that the absence of the promoter region and
      transcription of the LDLR gene is worse compensated than the synthesis of a
      defective LDL receptor.

PMID- 11298778
TI  - Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes.
AB  - BACKGROUND AND DESIGN: Conflicting data exist about uric acid levels in type 2
      diabetes mellitus, as low levels were found in diabetic patients, while elevated
      serum uric acid is a feature of hyperinsulinemia and impaired glucose tolerance.
      The present study was addressed to evaluate the relation between uric acid and
      metabolic parameters, creatinine clearance and albumin excretion rate in a cohort
      of type 2 diabetic patients. RESULTS: Hyperuricemic patients were older and had
      higher values of body mass index (BMI), systolic and diastolic blood pressure,
      triglycerides, albumin excretion rate, C-peptide and prevalence of hypertension,
      metabolic syndrome and macroalbuminuria and lower values of high-density
      lipoprotein (HDL)-cholesterol, creatinine clearance and glycated haemoglobin
      (HbA1c). The correlations between uric acid levels and triglycerides, BMI,
      systolic blood pressure, albumin excretion rate, C-peptide, creatinine clearance,
      HDL-cholesterol and HbA1c remained significant in a multiple regression analysis
      after adjustment for age, sex and duration of diabetes. After performing multiple
      logistic regression analyses, uric acid levels were independently associated with
      hypertension [odds ratio (OR) = 1.8; 95% confidence interval (CI) 1.6--2], after
      adjustment for age, sex, duration of diabetes and macroalbuminuria (OR = 1.5; 95%
      CI 1.1--2.0), after adjustment for age, sex, HbA1c levels, creatinine clearance,
      duration of diabetes and blood pressure levels and the metabolic syndrome (OR =
      1.6; 95% CI 1.5--1.8), after adjustment for age, sex and creatinine clearance.
      CONCLUSIONS: In type 2 diabetes, hyperuricemia seems to be associated with the
      insulin-resistant syndrome and with early onset or increased progression to overt
      nephropathy, while hypouricemia is associated with worse metabolic control,
      hyperfiltration and a late onset or decreased progression to overt nephropathy.

PMID- 11298779
TI  - Red wine protects diabetic patients from meal-induced oxidative stress and
      thrombosis activation: a pleasant approach to the prevention of cardiovascular
      disease in diabetes.
AB  - BACKGROUND: Oxidative stress and thrombosis have been reported to be increased in
      diabetic patients and involved in the pathogenesis of cardiovascular
      complications. It has been demonstrated in diabetic patients that consumption of
      a meal is accompanied by the generation of an oxidative stress and of a
      hypercoagulable state. It is well recognized that red wine shows antithrombotic
      activity and that its ingestion increases plasma antioxidant capacity in man. In
      this study the possibility that red wine consumption may reduce the oxidative
      stress and thrombosis produced postprandially in diabetic patients has been
      evaluated. SUBJECTS AND METHODS: Twenty type 2 diabetic patients were studied
      during fasting consumption of 300 mL of red wine, or during a meal accompanied,
      or not, by red wine ingestion. RESULTS: Plasma glucose, insulin, triglycerides,
      total plasma radical-trapping capacity, activated factor VII and prothrombin
      fragments 1 + 2 were measured in basal state and at 60, 120 and 180 min after the
      start of each experiment. Low-density lipoprotein (LDL) oxidation was also
      evaluated at baseline and after 120 min Plasma glucose, insulin, triglycerides
      and LDL oxidation significantly increased, while the total plasma radical
      trapping parameter significantly decreased during the meal test. Consumption of
      red wine in the fasting state significantly increased total plasma radical
      trapping parameter activity, while wine ingestion with a meal counterbalanced the
      decrease of total plasma radical-trapping parameter and the increase of LDL
      oxidation. Meal consumption induced an increase in plasma prothrombin fragments 1
      + 2 and activated factor VII in diabetic patients. Wine ingestion with the meal
      significantly reduced the production of both prothrombin fragments 1 + 2 and
      activated factor VII. Fasting consumption of red wine alone did not show effects
      on coagulation or LDL oxidation. CONCLUSION: This finding confirms that in the
      absorptive phase free radicals are produced in diabetic patients, which reduce
      serum antioxidant defences, increase LDL oxidation and activate the coagulation
      system. Red wine consumption during a meal significantly preserves plasma
      antioxidant defences and reduces both LDL oxidation and thrombotic activation.
      The consumption of a moderate amount of red wine during meals may have a
      beneficial effect in the prevention of cardiovascular disease in diabetic
      patients.

PMID- 11298780
TI  - Anabolic effects of rhIGF-I/IGFBP-3 in vivo are influenced by thyroid status.
AB  - BACKGROUND: There are close interrelationships between hormones that regulate
      bone formation and protein biosynthesis. For example, growth hormone and thyroid
      hormones can influence plasma levels of insulin-like growth factor-I (IGF-I). A
      patient's status regarding hormones other than IGF-I may thus indirectly modify
      the efficacy of IGF-I treatment. The aim of the current study was to determine if
      a statistical method could be used to identify key endocrine variables
      controlling an individual's response to IGF-I treatment. DESIGN: Biochemical
      profiles from the somatotropic, thyroid and adrenal axes were determined on two
      separate occasions in two different study cohorts. Each cohort was divided into
      four groups: placebo, low, medium and high dose of recombinant human IGF-I/IGF
      binding protein-3 (rhIGF-I/IGFBP-3). The relative changes in collagen C-terminal
      peptide (CICP) levels were explained as a function of the basal endocrine profile
      of each treated individual. This relationship was further examined in an
      experimental rat model, where undernourished rats were rendered hypothyroid by
      propylthiouracil and subsequently treated with rhIGF-I/IGFBP-3. RESULTS: The
      results of our statistical analysis in both cohorts indicated that each subject's
      response to rhIGF-I/IGFBP-3 administration was controlled in part by the
      individual's thyroid status prior to drug administration (r = 0.78 for both
      cohorts). The results from the animal study revealed that IGF-I treatment
      stimulated muscle protein synthesis by 35 +/- 9% (P = 0.05) in euthyroid rats but
      not in hypothyroid rats. CONCLUSION: The relationship between endocrine axes is
      not simple. An improved understanding of the interactions between neuroendocrine
      systems may facilitate the design of efficient drug regimens in the treatment of
      diseases such as osteoporosis and muscle wasting.

PMID- 11298781
TI  - Macrophage migration inhibitory factor in the sera and at the colonic mucosa in
      patients with ulcerative colitis: clinical implications and pathogenic
      significance.
AB  - BACKGROUND: Inflammatory cytokines produced by activated macrophages are
      implicated in the pathogenesis of ulcerative colitis (UC). With the theory that
      macrophage migration inhibitory factor (MIF) may have a role in the accumulation
      of macrophages, we studied MIF in UC. MATERIALS AND METHODS: A total of 27
      patients with UC, 14 patients with Crohn's diseases (CD), 11 patients with other
      forms of colitis and 26 normal controls were enrolled in the study. The levels of
      MIF in the sera and culture supernatant were measured by an enzyme-linked
      immunosorbent assay. MIF, macrophages and T cells were localized at the colonic
      mucosa by immunohistochemistry. RESULTS: The levels of MIF in the sera were
      significantly higher in UC than in normal controls (P < 0.05), in serum C
      reactive protein (CRP) -positive cases with UC than in CRP-negative cases with UC
      (P < 0.05), and in patients with severe colitis with UC than in mild colitis with
      UC (P < 0.05). There was a positive relationship between serum MIF levels with
      the CRP levels and activities of colitis. However, the levels of MIF in patients
      with CD and other forms of colitis were not significantly different from their
      levels in normal controls and UC. Infiltrating cells at the colonic mucosa in UC
      and CD expressed MIF. CONCLUSIONS: These data suggest a role of MIF in the
      pathogenesis of UC. MIF may be used as a marker of disease activity in UC and
      control of MIF production may have therapeutic implications.

PMID- 11298782
TI  - Phospholipase C activity of Helicobacter pylori is not associated with the
      presence of the cagA gene.
AB  - BACKGROUND: Knowledge about the possible role of phospholipase C (PLC) activity
      of microbial pathogens in the development of disease is increasing. Recently
      attention has focused on investigating PLC activity elaborated by Helicobacter
      pylori, but the role of this enzyme in H. pylori pathogenesis is still unknown.
      The aim of this study was to correlate PLC-activity of H. pylori on the basis of
      the cagA status with the clinical diagnosis of the patients. MATERIALS AND
      METHODS: Helicobacter pylori was isolated from patients with gastritis (G; n =
      38), duodenal ulcer (DU; n = 15), gastric ulcer (GU; n = 11) and gastric cancer
      (GC; n = 12). Polymerase chain reaction primers DZ3/R009 which amplified a 1350
      bp fragment were used to detect the cagA gene. PLC activity was determined using
      p-nitrophenylphosphorylcholine as substrate. RESULTS: Of the strains, 60% were
      cagA(+) and 40% were cagA(-). All strains showed PLC activity (2.20 +/- 0.91 U
      mg(-1) protein). PLC activity showed no association with the cagA status: cagA(+)
      (2.21 +/- 1.03 U mg(-1) protein), cagA(-) (2.18 +/- 0.79 U mg(-1) protein).
      Patients with GU had the highest PLC activity (2.77 +/- 1.26 U mg(-1) protein)
      and patients with GC had the lowest activity (1.8 +/- 0.57 U mg(-1) protein).
      CONCLUSIONS: Although PLC activity was present in all strains tested, it may only
      have pathological importance in patients with GU. However, the extent of PLC
      activity was independent of the presence of the cagA gene.

PMID- 11298783
TI  - Idiopathic chronic constipation: tachykinins as cotransmitters in colonic
      contraction.
AB  - BACKGROUND: Tachykinins (TKs) have been shown to be involved in the excitatory
      enteric motor pathway. This study aimed to examine the direct and nerve-mediated
      effect of specific NK1, NK2 and NK3 receptor agonists and antagonists in colonic
      preparations from control subjects and patients with idiopathic chronic
      constipation (ICC). MATERIALS AND METHODS: Cumulative concentrations of
      Sar9Met(O2)11 substance P (selective NK1 receptor agonist), [Ala5,beta-Ala8]
      neurokinin A (4-10) (selective NK2 receptor agonist) and [MePhe7]-neurokinin B
      (selective NK3 receptor agonist) were tested on colonic circular muscle strips to
      evaluate the direct drug effects. In addition, in the presence of atropine, the
      role of TKs in the off-contraction that follows the typical inhibitory response
      evoked by low frequencies of electrical field stimulation (0.5--10 Hz, 20 V, 1 ms
      pulse trains lasting 1 min) was investigated. RESULTS: In control preparations,
      the rank order of potency was: NK2 receptor-selective agonist > NK3 receptor
      selective agonist > NK1 receptor-selective agonist. The off-contraction was found
      to be reduced by about 30--40% in colonic circular muscle from ICC patients with
      respect to controls. Incubation with the NK1 receptor agonist did not modify the
      off-contraction measurements in either control or ICC preparations. Conversely,
      both NK2 and NK3 receptor agonists significantly (P < 0.01) increased the off
      contraction in ICC preparations only. This increased response was fully
      antagonized by MEN-10627, a NK2 and NK3 receptor antagonist depending on the
      dose. CONCLUSIONS: We may conclude that ICC is hyporesponsive to TKs and that the
      contractile reflex to distension is greatly reduced in ICC disease, but can be
      restored by incubation with NK2 and NK3 receptor agonists.

PMID- 11298784
TI  - Hepatic phenylalanine metabolism measured by the [13C]phenylalanine breath test.
AB  - BACKGROUND: The amino acid clearance test including phenylalanine is known to
      reflect liver functional reserve, which correlates with surgical outcome;
      however, the procedure is not clinically useful because of its laborious and time
      consuming nature. This study evaluates whether phenylalanine oxidation capacity
      measured by a breath test could reflect liver functional reserve. DESIGN: We
      determined phenylalanine oxidation capacity in 42 subjects using the L-[1
      13C]phenylalanine breath test (PBT). The 13CO2 breath enrichment was measured at
      10-min intervals for 120 min after oral administration of 100 mg of L-[1
      13C]phenylalanine. Subjects were divided into the following three groups
      according to their plasma retention rate of indocyanine green at 15 min (ICG
      R15): Group I (ICG R15 < 10%), Group II (ICG R15 10--20%), and Group III (ICG R15
      > 20%). First, we determined the parameters of the phenylalanine oxidation
      capacity that differentiated these groups and then, using these parameters, we
      compared the PBT with the ICG clearance test, Child-Pugh classification score and
      standard liver blood tests. RESULTS: The %13C dose h(-1) at 30 min and cumulative
      excretion at 80 min were significantly different among the three groups (P <
      0.05). These two parameters significantly correlated with the ICG R15, Child-Pugh
      classification score (P < 0.0001) and results of standard liver blood tests (P <
      0.05). CONCLUSIONS: Phenylalanine oxidation capacity measured by the PBT was
      reduced according to the severity of liver injury assessed by the ICG clearance
      test, Child-Pugh classification, and standard liver blood tests. These results
      indicate that the PBT can be used as a noninvasive method to determine liver
      functional reserve.

PMID- 11298785
TI  - Increased expression of VEGF following exercise training in patients with heart
      failure.
AB  - BACKGROUND AND AIMS: During the last decades several angiogenic factors have been
      characterized but so far it is unknown whether local muscle exercise training
      increases the expression of these factors in patients with moderate heart
      failure. Expression of the major putative angiogenic factor vascular endothelial
      growth factor (VEGF) at the level of messenger RNA (mRNA) and/or protein was
      therefore studied before and after 8 weeks of training in patient with chronic
      heart failure. METHODS: VEGF mRNA and protein concentrations were determined in
      skeletal muscle biopsies before and after 8 weeks of one-legged knee extension
      training in patients with chronic heart failure (New York Heart Association II
      III). RESULTS: Exercise training increased the citrate synthase activity and
      peripheral exercise capacity by 46% and 36%, respectively, in parallel with a two
      fold increase in VEGF at both the mRNA (P = 0.03) and protein (P = 0.02) levels
      CONCLUSION: The increase in VEGF gene expression in response to exercise training
      indicates VEGF to be one possible mediator in exercise-induced angiogenesis and
      may therefore regulate an important and early step in adaptation to increased
      muscle activity in patient with chronic heart failure.

PMID- 11298786
TI  - Effects of bile salts and aliphatic ionic surfactants on human lymphocyte
      proliferation.
AB  - BACKGROUND: The molecular mechanisms involved in the immunosuppressive properties
      of bile salts are partly unknown. METHODS: The aim of the study was to compare
      the effects of bile salts to those of various compounds with a steroid structure,
      or straight-chain hydrocarbons of different lengths and polar groups in the human
      mixed lymphocyte reaction. RESULTS: We showed a significant correlation between
      the effects of bile salts and a low critical micellar concentration, a high
      surface activity index, and the absence of conjugation. In addition to mixed
      lymphocyte reaction (MLR) inhibition, chenodeoxycholate (CDC) inhibit ConA
      induced IL2 production without any effect on IL2 R expression. Fusidate, a
      negatively charged steroid, with physical properties comparable to those of
      deoxycholate, had similar effects. Cetyltrimethylammonium bromide (CTAB), which
      exhibited a very low critical micellar concentration, inhibited mixed lymphocyte
      reaction in an extent comparable to cyclosporin A. In contrast, aliphatic
      compounds with critical micellar concentrations in the same range as bile salts
      but with a lower molecular area had no effect. CONCLUSIONS: Amphiphilic
      negatively charged molecules inhibit T-cell proliferation to an extent that is
      dependent upon their hydrophobicity. These results may be explained, at least in
      part, by a modification in the cell membrane lipid bilayer structure.

PMID- 11298787
TI  - Neurotrophins act at presynaptic terminals to activate synapses among cultured
      hippocampal neurons.
AB  - We have recently demonstrated that embryonic E16 hippocampal neurons grown in
      cultures are unable to form fast synaptic connections unless treated with BDNF or
      NT-3. This experimental system offers an opportunity to define the roles of
      neurotrophins in processes leading to formation of functional synaptic
      connections. We have used ultrastructural and electrophysiological methods to
      explore the cellular locations underlying neurotrophin action on synaptic
      maturation. The rate of spontaneous miniature excitatory postsynaptic currents
      (mEPSCs) evoked by hyperosmotic stimulation was 7-16-fold higher in neurotrophin
      treated cells than in controls. In addition, the potent neurotransmitter
      releasing drug alpha-latrotoxin was virtually ineffective in the control cells
      while it stimulated synaptic events in neurotrophin-treated cells. Likewise, the
      membrane-bound dye FM1-43 was taken up by terminals in neurotrophin-treated
      cultures five-fold more than in controls. Both the total number and the number of
      docked synaptic vesicles were increased by neurotrophin treatment. Activation of
      synaptic responses by neurotrophins occurred even when postsynaptic glutamate
      receptors and action potential discharges were pharmacologically blocked. These
      results are consistent with a presynaptic locus of action of neurotrophins to
      increase synaptic vesicle density which is critical for rapid synaptic
      transmission. They also suggest that neurotrophins can activate synapses in the
      absence of pre- and postsynaptic neuronal activity.

PMID- 11298788
TI  - NMDA-induced phosphorylation of the microtubule-associated protein MAP-2 is
      mediated by activation of nitric oxide synthase and MAP kinase.
AB  - Microtubule-associated protein MAP-2 is a neuronal phosphoprotein which modulates
      microtubule stability and spatial organization of signal transduction pathways.
      The functions of MAP-2 are modulated by phosphorylation. We studied the
      modulation of MAP-2 phosphorylation using the N-methyl- D-aspartate (NMDA) type
      of glutamate receptors and the signal transduction pathways mediating this
      modulation in primary cultures of rat cerebellar neurons. NMDA induced a rapid
      increase (330% of basal at 5 min) in MAP-2 phosphorylation which was not
      prevented by KN-62, indicating that it is not mediated by activation of Ca
      calmodulin-dependent protein kinase. NMDA-induced phosphorylation of MAP-2 was
      inhibited by the nitric oxide synthase inhibitors nitroarginine and 7
      nitroindazole and by PD098059 (an inhibitor of MAP kinase kinase), but was only
      slightly reduced by calphostin C or U-73122, inhibitors of protein kinase C and
      of phospholipase C, respectively. This indicates that the main pathway mediating
      NMDA-induced phosphorylation of MAP-2 is activation of nitric oxide synthase and
      subsequent activation of MAP kinase. We show that activation of NMDA receptors
      induces an activation of MAP kinase which is prevented by nitroarginine. The
      nitric oxide-generating agent (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) also
      induced activation of MAP kinase and increased phosphorylation of MAP-2. Other
      nitric oxide-generating agents (NOC-18 and NOR-3) also increased MAP-2
      phosphorylation. The interplay between NMDA receptors-associated signal
      transduction pathways and MAP-2 may be involved in the modulation of neuronal
      responses to extracellular signals and in the regulation of neuronal function.

PMID- 11298789
TI  - Phorbol esters promote postsynaptic accumulation of Vesl-1S/Homer-1a protein.
AB  - We examined effects of phorbol esters on the amount and the subcellular
      distribution of the activity-regulated protein Vesl-1S/Homer-1a in cultured
      hippocampal neurons. Major Vesl-1S immunoreactivity (IR) was detected throughout
      neuronal somata under control conditions. Bath application of phorbol esters, PMA
      and PDBu resulted in the increase in the amount of Vesl-1S proteins and promoted
      punctate distribution of Vesl-1S IR at the cortical regions of the neuronal
      somata. Immunofluorescent observations using antisynaptophysin and anti-Vesl-1S
      antibodies, and electron microscopic observations, revealed that Vesl-1S
      accumulated at postsynaptic regions following PMA application. Membrane
      depolarization with high concentrations of external potassium also promoted the
      punctate distribution of Vesl-1S IR. These results demonstrate that phorbol
      triggered reaction cascades result in the accumulation of Vesl-1S protein at
      postsynaptic regions, and suggest that these phorbol effects may mimic those
      caused by synaptic activities.

PMID- 11298790
TI  - Parallel fibre receptive fields of Purkinje cells and interneurons are climbing
      fibre-specific.
AB  - In cats decerebrated at the intercollicular level, the cutaneous parallel fibre
      receptive fields of Purkinje cells, molecular layer interneurons and Golgi cells
      in the cerebellar C3 zone were delineated by natural stimulation of the skin
      during extracellular unitary recordings. The locations of these receptive fields
      were compared with the climbing fibre receptive field of the local Purkinje cell
      and with the receptive fields of other neurons located along a beam of parallel
      fibres. The parallel fibre receptive fields of these neurons were highly specific
      to the local climbing fibre receptive field. In Purkinje cells, the parallel
      fibre receptive fields were located outside the climbing fibre receptive field of
      the same cell. In contrast, the parallel fibre receptive fields of interneurons
      were similar to the receptive field of the locally terminating climbing fibres.
      In both types of neurons, the parallel fibre receptive fields were small and had
      distinct borders. The location on the skin of the parallel fibre receptive fields
      differed conspicuously between neighbouring Purkinje cells and between
      neighbouring interneurons along a beam as well as between Purkinje cells and
      interneurons in the same electrode tracks. The remarkable specificity between the
      parallel fibre receptive fields in Purkinje cells and interneurons and the
      receptive field of the local climbing fibre is most easily explained by different
      forms of parallel fibre synaptic plasticity.

PMID- 11298791
TI  - Ca2+ signalling and changes of mitochondrial function during low-Mg2+-induced
      epileptiform activity in organotypic hippocampal slice cultures.
AB  - Several lines of evidence indicate that augmented neuronal activity is associated
      with increased mitochondrial function, however, the mechanisms of coupling are
      still unclear. In this study we used a low extracellular Mg2+ concentration and
      short stimulus trains to evoke neuronal hyperactivity in the form of seizure-like
      events (SLE) in hippocampal slice cultures. Simultaneous microfluorimetric and
      electrophysiological techniques were applied to gain insight into changes of Ca2+
      concentration in different compartments and into mitochondrial function. SLEs
      were associated with a large decrease of the extracellular Ca2+ concentration
      ([Ca2+]e), a spiking increase of the cytoplasmic and a smoothed elevation of the
      mitochondrial Ca2+ concentration (cytoplasmic concentration [Ca2+]i;
      intramitrochondrial concentration [Ca2+]m). Following an initial apparent decline
      in the mitochondrial membrane potential (DeltaPsi) and NAD(P)H autofluorescence,
      mitochondria depolarized and NADH production was augmented. Furthermore, SLEs
      were associated with increased oxidation of dihydroethidine (HEt). Our data
      suggest that intramitochondrial Ca2+ accumulation stimulates NADH production and
      production of radical oxygen species (ROS). Interestingly, mitochondrial
      depolarization followed [Ca2+]i and [Ca2+]m changes with a delay implying that
      electrogenic extrusion of Ca2+ from the mitochondrial matrix might be responsible
      for the depolarization of the mitochondrial membrane.

PMID- 11298792
TI  - BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation
      of GABA(A) receptor surface expression.
AB  - Changes in neurotransmitter receptor density at the synapse have been proposed as
      a mechanism underlying synaptic plasticity. Neurotrophic factors are known to
      influence synaptic strength rapidly. In the present study, we found that brain
      derived neurotrophic factor (BDNF) acts postsynaptically to reduce gamma
      aminobutyric acid (GABA)-ergic function. Using primary cultures of rat
      hippocampal neurons, we investigated the effects of BDNF on GABAergic miniature
      inhibitory postsynaptic currents (mIPSCs) and on the localization of GABAA
      receptors. Application of BDNF (100 ng/mL) led within minutes to a marked
      reduction (33.5%) of mIPSC amplitudes in 50% of neurons, recorded in the whole
      cell patch-clamp mode, leaving frequency and decay kinetics unaffected. This
      effect was blocked by the protein kinase inhibitor K252a, which binds with high
      affinity to trkB receptors. Immunofluorescence staining with an antibody against
      trkB revealed that about 70% of cultured hippocampal pyramidal cells express
      trkB. In dual labelling experiments, use of neurobiotin injections to label the
      recorded cells revealed that all cells responsive to BDNF were immunopositive for
      trkB. Treatment of cultures with BDNF reduced the immunoreactivity for the GABAA
      receptor subunits-alpha2, -beta2,3 and -gamma2 in the majority of neurons. This
      effect was detectable after 15 min and lasted at least 12 h. Neurotrophin-4 (NT
      4), but not neurotrophin-3 (NT-3), also reduced GABAA receptor immunoreactivity,
      supporting the proposal that this effect is mediated by trkB. Altogether the
      results suggest that exposure to BDNF induces a rapid reduction in postsynaptic
      GABAA receptor number that is responsible for the decline in GABAergic mIPSC
      amplitudes.

PMID- 11298793
TI  - Retrograde response of the rat facial motor nucleus to muscle inflammation
      elicited by phytohaemagglutinin.
AB  - To investigate whether motoneurons react to signals deriving from target
      inflammation, we studied the facial motor nucleus after injections of
      phytohaemagglutinin in the snout of adult rats. This plant lectin is a tool
      widely used to induce proliferation and activation of T lymphocytes, and we
      observed marked lymphocyte infiltration in the injected facial muscles.
      Retrograde labelling of motoneurons was not detected after peripheral injections
      of fluorochrome-conjugated phytohaemagglutinin. Nitric oxide synthase, revealed
      by NADPH-diaphorase histochemistry, OX-42-immunoreactive microglia, and
      expression of the cell death repressor gene bcl-2, investigated with
      nonradioactive in situ hybridization and immunohistochemistry, were evaluated in
      the facial nucleus. Daily phytohaemagglutinin injections for 4 days, mimicking
      repeated muscle exposure to inflammatory stimuli, resulted after 2-day survival
      in NADPH-diaphorase induction in motoneurons and marked activation of the
      surrounding microglia. Quantitative image analysis of NADPH-diaphorase staining,
      and OX-42 immunoreactivity and microglial cell counts indicated highly
      significant increases with respect to saline-injected control cases. The
      occurrence of a neuroprotective retrograde response was evaluated monitoring bcl
      2 expression. Following single phytohaemagglutinin administration, bcl-2 mRNA was
      significantly upregulated at 6 h in facial motoneurons and returned to basal
      levels at 24 h. Bcl-2 immunoreactivity was markedly upregulated at 24 h and was
      still significantly higher than in controls at 7 days, when concomitant NADPH
      diaphorase induction in motoneurons and microglia activation was also observed.
      No degenerative features were observed in motoneurons after phytohaemagglutinin
      injections at the examined time-points. The data point out that local muscle
      inflammation retrogradely elicits gene activation in motoneurons and their
      microenvironment.

PMID- 11298794
TI  - Corticotropin-releasing factor triggers neurite outgrowth of a catecholaminergic
      immortalized neuron via cAMP and MAP kinase signalling pathways.
AB  - Corticotropin-releasing factor (CRF), a neuropeptide of 41 amino acids, acts as
      the major physiological regulator of the basal and stress-induced release of
      corticotropin (ACTH), beta-endorphin and other proopiomelanocortin-derived
      peptides from the anterior pituitary gland. In addition to its endocrine
      activity, CRF displays extrahypophysiotropic effects, mainly as a regulator of
      stress responses. We show here that CRF may additionally function as a
      differentiating factor in immortalized noradrenergic neuronal CATH.a cells that
      express CRF receptor type I and resemble locus coeruleus-derived neurons. CRF
      triggers morphological changes in CATH.a cells including the appearance of
      extended long, slender neurites with prominent growth cones. CRF-treated CATH.a
      cells exhibit a morphology similar to locus coeruleus neurons in primary culture.
      CRF-induced neurite outgrowth of CATH.a cells was blocked by addition of
      inhibitors for cAMP-dependent protein kinase or extracellular signal-regulated
      protein kinase (ERK), a subtype of the mitogen-activated protein kinases. The
      participation of ERK within the CRF signalling cascade was further confirmed by
      Western blot experiments, with antibodies directed against the phosphorylated
      form of ERK, and also with transcription-based assays. We conclude that CRF
      functions as a differentiating factor of CATH.a cells via the cAMP and the MAP
      kinase signalling pathways.

PMID- 11298795
TI  - Abnormal trafficking and subcellular localization of an N-terminally truncated
      serotonin transporter protein.
AB  - We report here that a truncated 5-HTT protein is produced in the neurons of the
      raphe, in serotonin transporter (5-HTT) knockout (KO) mice. The 5-HTT gene has
      exon 2 deleted and we found that one main transcript, shortened by 450 bp, is
      produced in these KO mice. The mutated 5-HTT protein is only recognized by
      antibodies against the C-terminal portion of 5-HTT. This protein is not
      functional as there is no high-affinity serotonin uptake in 5-HTT KO mice, in
      adults or during development. Conversely, low-affinity serotonin uptake was
      detected in vitro, and in dopaminergic neurons of the substantia nigra in vivo.
      The truncated 5-HTT, recognized by antibodies to the C-terminus, is present
      exclusively in the somatodendritic compartment of the raphe neurons instead of
      being exported to axons. As shown with confocal and electron microscopy, the
      truncated 5-HTT does not reach the plasma membrane and is essentially retained in
      the endoplasmic reticulum. However, this does not seem to trigger refolding or
      degradation responses, as no upregulation of the chaperone BiP or of the
      degradation signal ubiquitin was detected. Last, as observed in heterozygous
      mice, the presence of the truncated 5-HTT protein, although produced in large
      quantities, does not disturb the normal trafficking of the wild-type protein.
      This study therefore validates the 5-HTT KO model despite the occurrence of an
      incomplete translation, and brings novel information on the in vivo 5-HT uptake
      and cellular processing of an abnormal 5-HTT protein.

PMID- 11298796
TI  - Reduction of metallothioneins promotes the disease expression of familial
      amyotrophic lateral sclerosis mice in a dose-dependent manner.
AB  - We previously reported that abnormal copper release from mutated Cu, Zn
      superoxide dismutase (SOD1) proteins might be a common toxic gain-of-function in
      the pathogenesis of familial amyotrophic lateral sclerosis (FALS) [Ogawa et al.
      (1997) Biochem. Biophys. Res. Commun., 241, 251-257.]. In the present study, we
      first examined metallothioneins (MTs), known to bind copper ions and decrease
      oxidative toxicity, and found a twofold increase in MTs in the spinal cord of the
      SOD1 transgenic mice with a FALS-linked mutation (G93A), but not in the spinal
      cord of wild-type SOD1 transgenic mice. We then investigated whether the clinical
      course of FALS mice could be modified by the reduced expression of MTs, by
      crossing the FALS mice with MT-I- and MT-II-deficient mice. FALS mice clearly
      reached the onset of clinical signs and death significantly earlier in response
      to the reduction of protein expression. These results indicated that the copper
      mediated free radical generation derived from mutant SOD1 might be related to the
      degeneration of motor neurons in FALS and that MTs might play a protective role
      against the expression of the disease.

PMID- 11298797
TI  - Kindling induces transient fast inhibition in the dentate gyrus--CA3 projection.
AB  - The granule cells of the dentate gyrus (DG) send a strong glutamatergic
      projection, the mossy fibre tract, toward the hippocampal CA3 field, where it
      excites pyramidal cells and neighbouring inhibitory interneurons. Despite their
      excitatory nature, granule cells contain small amounts of GAD (glutamate
      decarboxylase), the main synthetic enzyme for the inhibitory transmitter GABA.
      Chronic temporal lobe epilepsy results in transient upregulation of GAD and GABA
      in granule cells, giving rise to the speculation that following overexcitation,
      mossy fibres exert an inhibitory effect by release of GABA. We therefore
      stimulated the DG and recorded synaptic potentials from CA3 pyramidal cells in
      brain slices from kindled and control rats. In both preparations, DG stimulation
      caused excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential
      (IPSP) sequences. These potentials could be completely blocked by glutamate
      receptor antagonists in control rats, while in the kindled rats, a bicuculline
      sensitive fast IPSP remained, with an onset latency similar to that of the
      control EPSP. Interestingly, this IPSP disappeared 1 month after the last
      seizure. When synaptic responses were evoked by high-frequency stimulation, EPSPs
      in normal rats readily summate to evoke action potentials. In slices from kindled
      rats, a summation of IPSPs overrides that of the EPSPs and reduces the
      probability of evoking action potentials. Our data show for the first time that
      kindling induces functionally relevant activity-dependent expression of fast
      inhibition onto pyramidal cells, coming from the DG, that can limit CA3
      excitation in a frequency-dependent manner.

PMID- 11298798
TI  - Temperature and PMA affect different phases of exocytosis in bovine chromaffin
      cells.
AB  - Amperometry was used to study secretory kinetics of single bovine chromaffin
      cells stimulated by transient depolarizations at different temperatures. The
      initial rate of release was moderately enhanced when the temperature was raised
      from 18 to 22 and 37 degrees C. Secretion increased drastically at a later
      period, 5-10 s after the initiation of stimulus. Interestingly, incubation of the
      cells with phorbol 12-myristate 13-acetate (PMA) clearly enhanced fast secretory
      components. In addition, the rate of secretion of the slower component recruited
      by prolonged depolarizations (t > 30 s) was unaffected at the range of
      temperatures normally used in secretory experiments (22-37 degrees C). A
      'counting events' analysis of secretion, which avoids the influence of event
      charge changes, showed specific increases in a population of vesicles fusing
      between 7 and 12 s over the same range of temperatures, and a marked increase in
      vesicles fusing during the initial phase (1-5 s), of PMA-treated cell secretion.
      An analysis of temperature influence on transient components released by high
      sucrose, the secretion elicited by cell permeabilization with digitonin, and
      studies of the individual characteristics of amperometric events, allow us to
      conclude that an increase in the size of a secondary-released vesicle population
      is the main factor contributing to temperature-dependent enhancement of
      secretion, in clear contrast to the enhancement of fast releasable pools caused
      by phorbol esters.

PMID- 11298799
TI  - Spontaneous GABAergic postsynaptic currents in Cajal-Retzius cells in neonatal
      rat cerebral cortex.
AB  - Cajal-Retzius cells are among the first neurons appearing during corticogenesis,
      and play an important role in the establishment of cortical lamination. The
      variety of neurotransmitter receptors recently found on these cells imply that
      they are integrated in the neonatal cortical network. To investigate the presence
      and properties of spontaneous synaptic activity we performed whole-cell patch
      clamp recordings from visually identified and biocytin-labelled Cajal-Retzius
      cells in a tangential slice preparation of neonatal rat cerebral cortex
      (postnatal days P0-P5). Spontaneous postsynaptic currents (sPSCs) could be
      observed in about 23% of the cells using a pipette solution containing 136 m M Cl
      . The sPSCs occurred at a low frequency (0.07 +/- 0.07 Hz, n = 42 cells), had an
      average amplitude of 24.3 +/- 12.4 pA (n = 415 events) and could not be divided
      in subpopulations according to their amplitude distribution or kinetic
      properties. The sPSCs were blocked by the GABAA antagonist bicuculline (100
      microM), while the glutamatergic antagonists (+/-)-2-amino-5-phosphonopentatonic
      acid (APV, 30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM),
      as well as tetrodotoxin (1-2 microM), a blocker of voltage-gated sodium-currents,
      had no significant effect on sPSCs. The incidence rate of sPSCs declined within
      the age of the rats and no sPSCs could be observed after P4. These results
      suggest that Cajal-Retzius cells transiently receive action potential-independent
      and GABA(A) receptor-mediated spontaneous synaptic input, which may contribute to
      the refinement of cortical circuits.

PMID- 11298800
TI  - PSA-NCAM modulates BDNF-dependent survival and differentiation of cortical
      neurons.
AB  - We show that the loss or inactivation of the polysialic acid (PSA) tail of neural
      cell adhesion molecule (NCAM) on rat cortical neurons in culture leads to reduced
      differentiation and survival. The mechanism by which this negative effect is
      mediated appears to involve the neuronal response to brain-derived neurotrophic
      factor (BDNF): (i) in the absence of PSA or in the presence of excess free PSA
      added to the culture medium, BDNF-induced cell signalling is reduced; (ii) the
      addition of exogenous BDNF to the medium reverses the effect of PSA loss or
      inactivation. These data suggest that PSA-NCAM, previously shown to modulate cell
      migration and plasticity, is needed for an adequate sensitivity of neurons to
      BDNF.

PMID- 11298801
TI  - Perinatal changes of I(h) in phrenic motoneurons.
AB  - The hyperpolarization-activated cationic current (I(h)) was characterized and its
      maturation studied on phrenic motoneurons (PMNs), from reduced preparations of
      foetal (E18 and E21) and newborn (P0-P3) rats, using the whole-cell patch-clamp
      technique. In voltage-clamp mode, 2-s hyperpolarizing steps (5-mV, -50 to -110
      mV) elicited a noninactivating inward current, blocked by external application of
      Cs+ or ZD 7288. At -110 mV, Ih current density averaged 0.67 +/- 0.41 pA/pF at
      E18, reached a transient peak at E21 (1.38 +/- 0.11 pA/pF) and decreased at P0-P3
      (0.77 +/- 0.22 pA/pF). V1/2 was similar at E18 and E21 (-79 mV) but was
      significantly hyperpolarized at P0-P3 (-90 mV). The time constant of activation
      was voltage-dependent, and significantly faster at E21. Reversal potential was
      similar at all ages when estimated by extrapolation or tail current procedures.
      It was positively shifted by 25 +/- 6 mV when external potassium was raised from
      3 to 10 m M, suggesting a similar sensitivity to K+ from E18 to P0-3. Cs(+) or ZD
      7288 applications on PMNs at rest in current-clamp mode, in a partitioned
      chamber, induced a 10 +/- 2 mV hyperpolarization at E18 and E21, and an 8 +/- 2
      mV hyperpolarization at P0-3. The area of the central respiratory drive potential
      or current was increased by 33 and 31%, respectively, at E21, but was not
      significantly modified at E18 and P0-3. Our data suggest a critical period during
      the perinatal maturation of Ih during which it is transiently upregulated and
      attenuates the influence of the central respiratory drive on PMNs just prior to
      birth.

PMID- 11298802
TI  - Signals from cone photoreceptors to L-type horizontal cells are differentially
      modulated by low calcium in carp retina.
AB  - Ca2+ plays crucial roles in both phototransduction and calcium-dependent
      glutamate release from the photoreceptor terminal. Modulation, by lowering
      extracellular Ca2+, of red-sensitive (R-) and short wavelength-sensitive (S-)
      cone-driven light responses of L-type horizontal cells (LHCs) was studied in the
      isolated superfused carp retina using intracellular recording techniques. Low
      Ca2+ (nominally Ca2+-free) Ringer's reduced responses of LHCs to both green (500
      nm) and red (680 nm) flashes in darkness, with the former being suppressed more
      substantially than the latter. This differential suppression became more
      significant when contribution of R-cones to the green-light-induced responses was
      diminished by a moderate red (680 nm) background light. Application of IBMX, an
      inhibitor of phosphodiesterase (PDE), increased LHC responses to both red and
      green flashes equally, resembling the effect of low Ca2+ on phototransduction. In
      addition, photopic electroretinographic P III responses, reflecting the activity
      of cones, to red flashes were more potentiated by low Ca2+, compared to those to
      green flashes, whilst they were both equally potentiated by IBMX. Furthermore,
      low Ca2+ caused a more pronounced suppression of LHC responses to red flashes
      than those to green flashes in the presence of IBMX. It is postulated that
      reduction of LHC responses in low Ca2+ may be due to the 'saturation suppression'
      caused by the increased glutamate release from the photoreceptor terminal and the
      differential modulation may reflect a consequence of the dual action of low Ca2+
      on the PDE activity in the photoreceptor outer segment and the synaptic strength
      between cones and LHCs.

PMID- 11298803
TI  - NMDA-evoked calcium transients and currents in the suprachiasmatic nucleus:
      gating by the circadian system.
AB  - A variety of evidence suggests that the effects of light on the mammalian
      circadian system are mediated by glutamatergic mechanisms and that the N-methyl-
      D-aspartate (NMDA) receptor plays an important role in this regulation. One of
      the fundamental features of circadian oscillators is that their response to
      environmental stimulation varies depending on the phase of the daily cycle when
      the stimuli are applied. For example, the same light treatment, which can produce
      phase shifts of the oscillator when applied during subjective night, has no
      effect when applied during the subjective day in animals held in constant
      darkness (DD). We examined the hypothesis that the effects of NMDA on neurons in
      the suprachiasmatic nucleus (SCN) also vary from day to night. Optical techniques
      were utilized to estimate NMDA-induced calcium (Ca2+) changes in SCN cells. The
      resulting data indicate that there was a daily rhythm in the magnitude and
      duration of NMDA-induced Ca2+ transients. The phase of this rhythm was determined
      by the light-dark cycle to which the rats were exposed with the Ca2+ transients
      peaking during the night. This rhythm continued when animals were held in DD.
      gamma-Aminobutyric acid (GABA)ergic mechanisms modulated the NMDA response but
      were not responsible for the rhythm. Finally, there was a rhythm in NMDA-evoked
      currents in SCN neurons that also peaked during the night. This study provides
      the first evidence for a circadian oscillation in NMDA-evoked Ca2+ transients in
      SCN cells. This rhythm may play an important role in determining the periodic
      sensitivity of the circadian systems response to light.

PMID- 11298804
TI  - Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake
      cycle.
AB  - In the present study, cortical extracellular levels of glucose were monitored for
      the first time throughout the sleep-wake states of the freely moving rat. For
      this purpose, polygraphic recordings (electroencephalogram of the fronto
      occipital cortices and electromyogram of the neck muscles) were achieved in
      combination with differential normal pulse voltammetry (DNPV) using a specific
      glucose sensor. Data obtained reveal that the basal extracellular glucose
      concentration in the conscious rat is 0.59 +/- 0.3 m M while under chloral
      hydrate anaesthesia (0.4 g/kg, i.p.) it increases up to 180% of its basal
      concentration. Regarding the sleep-wake cycle, the existence of spontaneous
      significant variations in the mean glucose level during slow-wave sleep (SWS =
      +13%) and paradoxical sleep (PS = -11%) compared with the waking state (100%) is
      also reported. It is to be noticed that during long periods of active waking,
      glucose level tends towards a decrease that becomes significant after 15 min
      (active waking = -32%). On the contrary, during long episodes of slow-wave sleep,
      it tends towards an increase which becomes significant after 12 min (SWS = +28%).
      It is suggested that voltammetric techniques using enzymatic biosensors are
      useful tools allowing direct glucose measurements in the freely moving animal. On
      the whole, paradoxical sleep is pointed out as a state highly dependent on the
      availability of energy and slow-wave sleep as a period of energy saving.

PMID- 11298805
TI  - Dorsal hippocampal lesions impair appetitive classical conditioning to localized
      cues.
AB  - Three experiments examined appetitive classical conditioning in rats with small
      electrolytic lesions of the dorsal hippocampus. In all the experiments, the
      reinforcer was food delivery and the conditioned response (CR) entry to the food
      tray; the three experiments differed in the nature of the conditioned stimulus
      (CS). When this was a small light located inside the food tray, conditioning was
      impaired in lesioned animals, but when the CS was a general increase in
      illumination, they learned at the same rate as controls. With a white noise as
      the CS, learning was significantly faster in lesioned subjects. These data
      demonstrate that lesions of the dorsal hippocampus can produce impairments in
      appetitive delay conditioning, but only with certain types of CS. It is suggested
      that deficits are found with CSs that are localized in space.

PMID- 11298806
TI  - SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety
      and blocks the hyperphagic effect of orexin-A in rats.
AB  - Intracerebroventricular (i.c.v.) administration of the novel hypothalamic
      neuropeptide orexin-A stimulates food intake in rats, and delays the onset of
      behavioural satiety (i.e. the natural transition from feeding to resting).
      Furthermore, preliminary findings with the selective orexin-1 receptor
      antagonist, SB-334867, suggest that orexin-A regulation of food intake is
      mediated via the orexin-1 receptor. At present, however, little is known about
      either the intrinsic effects of SB-334867 on the normal structure of feeding
      behaviour, or its effects upon orexin-A-induced behavioural change. In the
      present study, we have employed a continuous monitoring technique to characterize
      the effects of SB-334867 (3-30 mg/kg, i.p.) on the microstructure of rat
      behaviour during a 1-h test with palatable wet mash. Administered alone, SB
      334867 (30 mg/kg, but not lower doses) significantly reduced food intake and most
      active behaviours (eating, grooming, sniffing, locomotion and rearing), while
      increasing resting. Although suggestive of a behaviourally nonselective (i.e.
      sedative) action, the structure of feeding behaviour was well-preserved at this
      dose level, with the reduction in behavioural output clearly attributable to an
      earlier onset of behavioural satiety. As previously reported, orexin-A (10 microg
      per rat i.c.v.) stimulated food intake, increased grooming and delayed the onset
      of behavioural satiety. Pretreatment with SB-334867 dose-dependently blocked
      these effects of orexin-A, with significant antagonism evident at dose levels (3
      10 mg/kg) below those required to produce intrinsic behavioural effects under
      present test conditions. Together, these findings strongly support the view that
      orexin-A is involved in the regulation of feeding patterns and that this
      influence is mediated through the orexin-1 receptor.

PMID- 11298807
TI  - Fear memory retrieval induces CREB phosphorylation and Fos expression within the
      amygdala.
AB  - Fear memory retrieval has been shown to induce a protein-synthesis dependent re
      consolidation of memories within the amygdala. Here, using immunocytochemistry,
      we investigated the molecular basis of this process in the rat and show that
      retrieval of a cued fear memory induces the activation, by phosphorylation, of
      the transcription factor CREB within the basal and lateral nuclei of the
      amygdala, as well as expression of the CREB-regulated immediate-early gene, c
      fos, in the basal amygdala. We also show an increase in CREB phosphorylation
      within the central nucleus of the amygdala following behavioural testing, with an
      accompanying increase in Fos-immunoreactive nuclei in animals retrieving the cued
      association. There were no changes in either phosphorylated CREB or Fos in the
      hippocampus following exposure to discrete fear stimuli. These results show that
      activation of CREB, which has been shown to be involved in the formation of long
      term fear memories, also accompanies memory retrieval, and also suggest a role
      for CREB phosphorylation in memory re-consolidation following retrieval.

PMID- 11298808
TI  - Regulation of SSAT expression by synaptic activity.
AB  - Neuronal activity is a requirement for the plasticity and normal development of
      the central nervous system. We have used differential cloning techniques to
      identify an immediate-early gene (IEG) that is rapidly induced in neurons by
      activity in both adult and developmental models of plasticity. Here we describe
      the key regulatory enzyme of polyamine catabolism, spermidine/spermine N1
      acetyltransferase (SSAT), as a neuronal IEG. In the rat brain, kainate-induced
      seizures result in a 5.5-fold increase in the amount of SSAT mRNA above basal
      levels and the enzymatic activity is increased twofold. Expression of SSAT mRNA
      is rapidly and transiently upregulated in the cerebral cortex and hippocampus by
      seizure-induced neuronal activation. In hippocampal neurons, SSAT expression is
      dynamically responsive to synaptic activity in the long-term potentiation (LTP)
      paradigm. In developing brain, region-specific expression of SSAT mRNA is first
      detected at postnatal day 9 (P9) and subsequently increases through days P15,
      P20, before reaching maximal level in adult animals. This dynamic transcriptional
      and translational control suggests that SSAT may play a role in activity
      dependent neuronal plasticity and development.

PMID- 11298809
TI  - Novelty enhances retrieval: molecular mechanisms involved in rat hippocampus.
AB  - Rats exposed to a novel environment just prior to or 1-2 h, but not 4 or 6 h,
      before retention testing exhibited an enhanced retrieval of a one-trial
      inhibitory avoidance training. The bilateral intrahippocampal infusion of
      PD098059, an inhibitor of mitogen-activated protein kinase (MAPK), the specific
      upstream activator of p42 and p44 MAPKs, given 10 min before the exposure to the
      novel environment, blocked the enhancing effect of novelty on memory retrieval.
      In addition, prenovelty infusion of DL-2-amino-5-phosphonovalerate (APV), an
      antagonist of glutamate NMDA receptors, produced similar effects. The exposure to
      the novel environment is associated with an activation of p42 and p44 MAPKs and
      an increase in the phosphorylation state of the transcription factor cAMP
      response element binding protein (CREB). No changes were observed in cAMP
      dependent protein kinase (PKA) activity or in alpha-CAMKII activation. Taken
      together, our results indicate that novelty activates hippocampal MAPKs, which
      are necessary, along with glutamate NMDA receptors, for the enhancing effect of
      novelty on retrieval.

PMID- 11298810
TI  - Cooperation and conflict in the evolution of multicellularity.
AB  - Multicellular organisms probably originated as groups of cells formed in several
      ways, including cell proliferation from a group of founder cells and aggregation.
      Cooperation among cells benefits the group, but may be costly (altruistic) or
      beneficial (synergistic) to individual cooperating cells. In this paper, we study
      conflict mediation, the process by which genetic modifiers evolve that enhance
      cooperation by altering the parameters of development or rules of formation of
      cell groups. We are particularly interested in the conditions under which these
      modifiers lead to a new higher-level unit of selection with increased cooperation
      among group members and heritable variation in fitness at the group level. By
      sculpting the fitness variation and opportunity for selection at the two levels,
      conflict modifiers create new functions at the organism level. An organism is
      more than a group of cooperating cells related by common descent; organisms
      require adaptations that regulate conflict within. Otherwise their continued
      evolution is frustrated by the creation of within-organism variation and conflict
      between levels of selection. The evolution of conflict modifiers is a necessary
      prerequisite to the emergence of individuality and the continued well being of
      the organism. Conflict leads--through the evolution of adaptations that reduce i-
      to greater individuality and harmony for the organism.

PMID- 11298811
TI  - A review of host major-gene resistance to potato viruses X, Y, A and V in potato:
      genes, genetics and mapped locations.
AB  - In view of modern developments in the technologies available for breeding
      potatoes for resistance to virus diseases, it is timely to review the host major
      genes that confer resistance, in Solanum species, to potato viruses X, Y, A and V
      (the viruses for which the resistance genes have been most extensively studied).
      Over the course of 60 years, many such genes in Solanum species have been
      characterized: a comprehensive list is presented. Inheritance studies are
      reviewed, including linkage studies and molecular mapping, and the positions of
      resistance genes mapped so far are listed. It is apparent from recent research
      that disease resistance genes are often clustered in particular regions of the
      chromosomes; the significance of these resistance gene clusters is discussed. The
      information presented will be useful for potato breeding, and for genetic and
      mapping studies and gene cloning.

PMID- 11298812
TI  - Breeding virus resistant potatoes (Solanum tuberosum): a review of traditional
      and molecular approaches.
AB  - Tetraploid cultivated potato (Solanum tuberosum) is the World's fourth most
      important crop and has been subjected to much breeding effort, including the
      incorporation of resistance to viruses. Several new approaches, ideas and
      technologies have emerged recently that could affect the future direction of
      virus resistance breeding. Thus, there are new opportunities to harness molecular
      techniques in the form of linked molecular markers to speed up and simplify
      selection of host resistance genes. The practical application of pathogen-derived
      transgenic resistance has arrived with the first release of GM potatoes
      engineered for virus resistance in the USA. Recently, a cloned host virus
      resistance gene from potato has been shown to be effective when inserted into a
      potato cultivar lacking the gene. These and other developments offer great
      opportunities for improving virus resistance, and it is timely to consider these
      advances and consider the future direction of resistance breeding in potato. We
      review the sources of available resistance, conventional breeding methods, marker
      assisted selection, somaclonal variation, pathogen-derived and other transgenic
      resistance, and transformation with cloned host genes. The relative merits of the
      different methods are discussed, and the likely direction of future developments
      is considered.

PMID- 11298813
TI  - Genetic variation within and between populations of Pinus sylvestris L. (Scots
      pine) for susceptibility to Melampsora pinitorqua Rostr. (pine twist rust).
AB  - The genetic variability of Scots pine (Pinus sylvestris L.) for twist rust
      susceptibility and the consequences for genetic improvement of the species were
      evaluated after artificial inoculation of 1-year-old seedlings in greenhouse
      tests. Wind-pollinated progenies, factorial and incomplete diallel mating designs
      were used to compare two natural populations of Scots pine (Haguenau, France, and
      Taborz, Poland) and their hybrids (Haguenau x Taborz). Families from Taborz were
      significantly (P < 0.001) less susceptible to twist rust than those from
      Haguenau. Inter-population hybrids were as susceptible as the Haguenau
      population. No clear relationship between severity of infection, shoot length and
      phenological stage at time of inoculation was observed in intra- and
      interpopulation crosses. Differences observed between the two natural populations
      for their response to twist rust are suggested to be the consequence of local
      adaptation simultaneously for climatic conditions and pathogen pressure. Within
      each of the two populations, the effects of general combining abilities (GCA) for
      rust susceptibility were predominant, although estimation of individual
      heritabilities remained at a moderate level (0.30-0.54). In interpopulation
      crosses, GCA effects of Haguenau and Taborz populations were still predominant.
      Moreover, hybrid performance could be predicted with confidence based on the
      intrapopulation GCA values of parents. Genetic gain on twist rust resistance
      could be achieved quickly through intrapopulation mass or backward selection
      based on wind-pollinated progeny tests.

PMID- 11298814
TI  - The subspecific origin of the inland breeding colonies of the cormorant
      Phalacrocorax carbo in Britain.
AB  - The establishment of cormorant breeding colonies inland within south-east Britain
      since 1981 is a matter of major conservation and pest management concern. This
      study was initiated to investigate the subspecific origin of two recently
      established breeding colonies. The analysis examined sequence variation of the
      control (D-loop) region of the mitochondrial genome. Samples of tissue were
      obtained from 334 individuals from across the species range in western Europe
      from both subspecies (Phalacrocorax carbo carbo and P. c. sinensis) and 84 birds
      from two inland breeding colonies in Britain. Single-strand conformation
      polymorphism (SSCP) was used to assess mitochondrial variation among samples,
      revealing four haplotypes. The samples from the traditional breeding colonies
      clustered into three distinct phylogeographic groupings: Norway-Scotland, Wales
      England-Iles des Chausey and the rest of Continental Europe. These results only
      partly agree with the traditional subspecific taxonomic groupings and are
      slightly at variance with results using microsatellite DNA frequencies, and a
      hypothesis using results from both studies is advanced. The subspecific origin of
      the inland colonies was investigated using maximum likelihood and Bayesian
      models.

PMID- 11298815
TI  - A molecular phylogeographic perspective on a fifty-year-old taxonomic issue in
      grasshopper systematics.
AB  - This paper addresses a decades-old taxonomic controversy surrounding a species in
      the grasshopper subfamily Melanoplinae. Melanoploid grasshoppers fall into two
      tribes, the Nearctic-restricted Melanoplini and the Holarctically distributed
      Podismini. The current view regarding one member, Bohemanella frigida, is that it
      belongs to the latter tribe and that North American populations were established
      by dispersal from Eurasia via the Bering Land Bridge. Over the past 50 years,
      this opinion has changed a few times; this species was once regarded as part of
      the tribe Melanoplini and, as such, deemed to be the only Holarctically
      distributed Orthopteran insect with New World antecedents. A molecular
      phylogenetic study of this species was thus performed to verify its phylogenetic
      position and to establish a probable direction of dispersal. Portions of three
      mitochondrial genes (cyt b, COII, and ND2) were sequenced and phylogenetically
      analysed using weighted and unweighted parsimony, neighbour-joining, and maximum
      likelihood methods. Support for the inclusion of B. frigida within the tribe
      Melanoplini and the use of its original name, Melanoplus frigidus, was strong
      using all methods. Placement in the tribe Melanoplini leads to an acceptance of
      an earlier hypothesis regarding direction of dispersal across the Bering Land
      Bridge, making this grasshopper a unique case in orthopteran insects in this
      respect.

PMID- 11298816
TI  - High resolution microsatellite based analysis of the mating system allows the
      detection of significant biparental inbreeding in Caryocar brasiliense, an
      endangered tropical tree species.
AB  - In this work we investigate the mating system of four populations of the
      endangered tropical tree species Caryocar brasiliense, using genetic data from 10
      microsatellite loci. Eight to 10 open-pollinated progeny arrays of 16
      individuals, together with their mother tree, were sampled per population. Mating
      system parameters were estimated under the mixed mating model, implemented by the
      software MLTR. The single-locus outcrossing rate (ts) varied among loci and
      populations, but multilocus outcrossing rates (tm) were equal to one for all four
      populations. Nevertheless, biparental inbreeding (tm - ts) was different from
      zero for all populations, indicating that outcrossing events may occur between
      relatives. Our results also indicate that the high polymorphism of microsatellite
      markers provide an extraordinary resolution to discriminate precisely selfing
      events from outcrossing events between close relatives. Our results indicate
      that, although highly outcrossed, C. brasiliense shows high levels of biparental
      inbreeding, most likely due to the limited flight range of pollinators and
      restriction in seed dispersal. Furthermore, these results suggest that Cerrado
      fragmentation could limit gene flow by isolating seed dispersers and territorial
      small sized bat pollinators inside fragments, increasing the rate of mating
      between close relatives. The conservation of nonisolated populations in large
      preserved areas may be necessary to foster outcrossing events between unrelated
      individuals and thus maintain species viability.

PMID- 11298817
TI  - Courtship songs of Drosophila pseudoobscura and D. persimilis. II. Genetics of
      species differences.
AB  - Although male courtship songs have been repeatedly implicated in sexual isolation
      between numerous Drosophila species, no genetic studies have evaluated the
      genetic basis of differences between species beyond using quantitative genetic
      analyses of hybrids or surveying associations of song characters to five or fewer
      genetic markers. Here, we dissect the genetic basis of the difference between D.
      pseudoobscura and D. persimilis in two courtship song elements (interpulse
      interval and intrapulse frequency) using 15 molecular markers. We also evaluate
      the association between song elements and sexual isolation in these backcross
      hybrid males of these species. We find that song differences between these
      species are associated with at least two or three genomic regions, and the
      species difference in interpulse interval may be oligogenic. Courtship song
      differences are especially strongly associated with two inversions that
      differentiate these species. Further, we found that interpulse interval is
      strongly associated with mating success to D. pseudoobscura females, while
      intrapulse frequency is associated with mating success to D. persimilis females.
      Implications of these findings are discussed.

PMID- 11298818
TI  - Capitulum characters in a seed heteromorphic plant, Crepis sancta (Asteraceae):
      variance partitioning and inference for the evolution of dispersal rate.
AB  - In Crepis sancta (Asteraceae), achenes produced in the periphery of the flower
      head have reduced dispersal ability and are larger than achenes produced in the
      centre of the head, which disperse farther. The proportion of central achenes
      produced by a single individual represents the potential dispersal rate of its
      progeny. Seed variation in dispersal ability may be important where there is
      spatio-temporal variability of habitats, but its evolutionary significance mainly
      depends on the heritability of the relative proportions of each achene morph.
      However, the number of peripheral achenes in a capitulum, and that of involucral
      bracts are suggested to depend on the number of parastichies, a canalized
      character. From a diallel cross design, phenotypic variance for several capitulum
      traits was partitioned among six variance components, including the additive
      variance. The phenotypic values of some head traits reflected the expected
      frequency due to ontogeny, in particular the number of involucral bracts. Yet,
      this character also had a significant heritability, suggesting that variation
      around the mode of the distribution was not only due to developmental noise. The
      additive variance for number of peripheral and central achenes was not
      significantly different from zero. In contrast, their respective proportion had a
      narrow sense heritability greater than 0.20. The present results suggest that the
      percentage of central achenes per individual, and thus the potential dispersal
      rate in Crepis sancta, is under quantitative genetic control, and could undergo
      microevolutionary changes in natural populations.

PMID- 11298819
TI  - Allozyme analysis of the hybrid origin of Arisaema ehimense (Araceae).
AB  - Allozyme diversity was examined in the Japanese jack-in-the pulpit species,
      Arisaema serratum and A. tosaense, and their putative hybrid species, A. ehimense
      (all diploid). Arisaeme ehimense contains mostly alleles found in one or both of
      the putative parent species but few unique alleles, partially supporting the
      hypothesis that A. ehimense is of hybrid origin from the two species, although
      the possibility that A. ehimense arose via divergent speciation cannot be
      excluded. Because only limited information was gained from the survey of allozyme
      variation, additional taxon-specific markers from A. serratum and A. tosaense are
      required to test rigorously the hybrid origin of A. ehimense. A phenogram based
      on allele frequencies suggested that introgression occurs between A. serratum and
      A. tosaense where these species are sympatric.

PMID- 11298820
TI  - Geographical patterns of genetic subdivision in the cellar spider Pholcus
      phalangioides (Araneae).
AB  - Geographical patterns of gene flow and drift were analysed in the commensal
      cellar spider Pholcus phalangioides to get insight into the causes affecting
      genetic variation in this species strictly associated with man. Our sampling
      consisted of 23 subpopulations collected over five urban regions in central
      Europe (distances ranged from 920 km to sites within the same building complex).
      Five variable allozyme loci showed significant interpopulation subdivision
      (theta=0.146) and isolation by distance over the area studied. On a regional
      scale (up to 70 km) significant differentiation was found, but the genetic
      pattern did not correlate with distance. Moreover, significant two-locus
      disequilibria were detected and a recent reduction in the effective population
      size was indicated within six sites. These results suggest that in P.
      phalangioides a high potential of dispersal and strong effects of drift within
      small, demographically unstable mating units seem to cause significant, but
      unpredictable genetic differentiation patterns at lower geographical scales. Our
      study documents strong effects of drift in a strictly commensal species outside
      the murine rodents.

PMID- 11298821
TI  - Genetic interchange of Dreissena polymorpha populations across a canal.
AB  - The zebra mussel Dreissena polymorpha, has been invading western Central Europe
      since the early 19th century, coming from the Pontocaspian by two routes, each
      interconnected by large rivers and canals constructed at that time. By 1992 these
      two invasion populations had been given the opportunity to mix extensively across
      the newly built Main-Danube canal. Different hypotheses about the dynamics of
      genetic interchange have been postulated, ranging from a stable intergradation
      zone to complete mixing. We analysed the allozyme variation at nine loci in 14 or
      17 populations, respectively, across the canal on two occasions: 2(1/2) years and
      4(1/2) years after the opening. At the first sampling a strong genetic
      differentiation at three loci was found between the two invasion lines. This
      differentiation declined during the two-year period. The main effect was an
      assimilation of the Main populations according to the gene frequencies of the
      Danube populations, which suggest a swamping of the Main populations by Danube
      type larvae. This inference is congruent with the overall water flow regime
      across the canal, i.e. active pumping from the Danube into the Main drainage
      system. The observed interchange processes allow some inferences to be made about
      the selective significance of the highly heterozygous allozyme loci in D.
      polymorpha.

PMID- 11298822
TI  - I-R system of hybrid dysgenesis in Drosophila melanogaster: analysis of the
      mitochondrial DNA in reactive strains exhibiting different potentials for I
      factor transposition.
AB  - In the I-R hybrid dysgenesis system, Drosophila melanogaster strains fall into
      two categories denoted inducer (I) and reactive (R). Among the reactive strains
      we can distinguish strains with weak, medium or strong reactivity levels. These
      levels are inherited in a complex way involving both chromosomal and
      nonchromosomal determinants, the nonchromosomal determinant being mainly
      maternally inherited. We were interested in determining the molecular basis of
      this maternal transmission. In this article we analyse the possible implication
      of the mitochondrial DNA in the determination of the reactivity levels. The mtDNA
      was analysed in lines with very different reactivity levels with the aim of
      correlating sequence differences with reactivity levels. The mtDNA was analysed
      by sequencing and restriction fragment length. No correlation was established
      between reactivity level and mtDNA sequence. This may favour the hypothesis that
      epigenetic changes would be responsible for the different reactivity levels and
      their transgenerational transmission.

PMID- 11298823
TI  - In vivo maturation and migration of dendritic cells.

PMID- 11298824
TI  - Rewiring of CD40 is necessary for delivery of rescue signals to B cells in
      germinal centres and subsequent entry into the memory pool.
AB  - Memory B-cell development is impaired by in vivo blockade of the CD40-CD40 ligand
      (CD40L) interaction using human Fc immunoglobulin G1 (IgG1)-mouse CD40 fusion
      protein (CD40-Ig); however, germinal centre (GC) formation is not. We show here
      that the block in B-cell differentiation in these mice is at the stage of rescue
      from apoptosis and exit from the GC. Thus, GC from CD40-Ig-treated mice contain a
      three- to fourfold higher level of apoptotic cells than found in control mice
      injected with human IgG1 alone. This increase in apoptosis is not caused by a
      blockade of the CD40L-mediated rescue signal but is the result of an intrinsic
      defect of GC B cells in CD40-Ig-treated mice to receive rescue signals via CD40.
      While anti-CD40 stimulation maintained the viability in culture of GC B cells
      from control mice, it did not rescue GC B cells from CD40-Ig-treated mice. This
      data is consistent with the notion that a 'rewiring' of the CD40 molecule is
      induced by CD40 ligation early in the response and is necessary to allow B-cell
      rescue from apoptosis when they subsequently enter the GC.

PMID- 11298825
TI  - Molecular structure of eight human autoreactive monoclonal antibodies.
AB  - The heavy (H) and light (L) chain V-region sequences of eight human autoreactive
      immunoglobulin M (IgM) monoclonal antibodies (mAbs: BY-4, BY-7, BY-12, IRM-3, IRM
      7, IRM-8, IRM-10 and CDC-1) were determined at the cDNA level. All VH and VL
      families were identified. Four different VH families were represented, VH3 being
      the most common as five of the mAbs (BY-7, BY-12, IRM-3, IRM-8 and CDC-1) used
      genetic elements of this family, whereas VH1, VH2 and VH4 were only present in
      IRM-7, BY-4 and IRM-10, respectively. BY-4, BY-7, BY-12, IRM-7 and IRM-10 reacted
      with a variety of self as well as non-self antigens, thus exhibiting polyreactive
      behaviour. Comparison of the gene segments utilized by these mAbs with their
      germline counterparts revealed that the gene segments were close to germline
      configuration. The length of H-CDR3 was found to be relatively long (27-60
      nucleotides) among the polyreactive mAbs and the presence of Tyr and Trp residues
      in this region seems to be of vital importance for polyreactivity. We have
      analysed the utilization of gene elements and the presence of amino acid residues
      in regions particularly important for antigen binding, such as CDR. Common
      molecular features relating to the function of the mAbs are discussed.

PMID- 11298826
TI  - Metalloprotease inhibitor-mediated inhibition of mouse immunoglobulin production.
AB  - High levels of membrane CD23 have been shown to decrease immunoglobulin E (IgE).
      CD23 is a very labile molecule and is cleaved from the cell surface by an unknown
      metalloprotease. Two metalloprotease inhibitors, compound A (N-[4-hydoxyamino-2
      (R)-isobutyl-3-(S)propargylthiomethylsuccinyl]-(S)-phenylalnine-N'-methyl-amide)
      and compound B (N-[3-(S)-hydroxy-4-hydroxyamino-2-(R)-(2-naphthylmethyl)
      succinyl]-(S)-tert-leucinamide), were chosen for their ability to inhibit human
      CD23 cleavage and selectively inhibit IgE production. The ability of these
      inhibitors to block cleavage of murine CD23 and immunoglobulin production in an
      in vitro system was examined. The inhibitors blocked sCD23 release from B cells.
      The inhibitors also decreased IgE production by B cells; however, 20-30 times
      more inhibitor was needed to give a similar amount of inhibition as compared with
      sCD23 release. The effects on immunoglobulin production did not require the
      presence of CD23 in that these inhibitors also blocked in vitro immunoglobulin
      production when B cells from CD23-/- mice were used. The inhibitors decreased
      production of all other immunoglobulin isotypes examined and reduced the number
      of IgE antibody-forming cells (AFC) while having no effect on cell proliferation
      or viability. The level of Iepsilon transcripts in cells treated with compounds A
      and B were not different as compared with control cells. These results suggest
      that while these inhibitors effectively inhibit IgE production in a CD23-specific
      manner in the human, these compounds, in the mouse, inhibit immunoglobulin
      production by an unknown mechanism that is unrelated to CD23.

PMID- 11298827
TI  - Functional dissection of the cytoplasmic subregions of the interleukin-5 receptor
      alpha chain in growth and immunoglobulin G1 switch recombination of B cells.
AB  - The interleukin-5 receptor alpha chain (IL-5Ralpha) is known to regulate the
      development and function of B cells and eosinophils. Although the functions of IL
      5Ralpha cytoplasmic domain subregions have been studied extensively using
      cultured cell lines, this approach has limitations when studying the functions of
      distinct primary B-cell subpopulations and their responsiveness to IL-5. In the
      present study, we generated mice on an IL-5Ralpha null background, each
      expressing a mutant form of an IL-5Ralpha transgene ligated to a mu enhancer and
      VH promoter, either lacking the cytoplasmic DC3 region or substituting two
      proline residues for alanine (ApvA) in the membrane-proximal ppvp motif of the
      cytoplasmic domain. The ppvp motif, which mediates activation of JAK2/STAT5 and
      Btk, also contributes to c-fos, c-jun and c-myc expression. IL-5Ralpha null
      mutant mice showed impaired B-1-cell development, reduced serum immunoglobulin G3
      (IgG3) and IgM, no IL-5-induced enhancement of B-cell proliferation and IL-5
      induced switch recombination from the mu gene to gamma1 gene; these were not
      recovered following the expression of the ApvA mutant. In contrast, absence of
      the DC3 region affected the IL-5-induced switch recombination from the mu to the
      gamma1 gene and B-1-cell development, while IL-5-induced proliferation and IgM
      production were at levels similar to those of B cells expressing wild-type IL
      5Ralpha transgene. The results clearly indicated that the ppvp motif and the DC3
      region of IL-5Ralpha played distinct roles in B-cell proliferation and
      differentiation. Thus, this present approach offers new insights into the
      functions of the cytoplasmic subregions of IL-5Ralpha, in particular its carboxy
      terminal region.

PMID- 11298829
TI  - Transforming growth factor-beta promotes 'death by neglect' in post-activated
      human T cells.
AB  - Transforming growth factor-beta (TGF-beta) is central to the wound repair
      processes that follow local trauma and inflammation. In order to mimic the early
      events of wound-healing, we studied the effects of TGF-beta on mitogen-stimulated
      peripheral blood cells. TGF-beta added at the initiation of mitogenesis did not
      significantly alter T-cell activation, proliferation, CD45 isoform switching, or
      activation-induced cell death. By contrast, TGF-beta added 72 hr post-activation
      (or later) enhanced the cumulative increase in apoptotic T cells. TGF-beta had no
      effect on mitogen-induced up-regulation of Fas (CD95) or Fas ligand and did not
      enhance killing of the Fas-sensitive Jurkat cell line by activated T cells.
      Furthermore, TGF-beta had no direct effect on levels of mRNA for members of the
      bcl family (bcl-X, bfl-1, bik, bak, bax, bcl-2 and mcl-1). These findings suggest
      that TGF-beta does not directly induce apoptosis via the Fas system or by direct
      effects on bcl proteins. However, interleukin-2, which can 'rescue' lymphocytes
      from spontaneous apoptosis due to cytokine deprivation, abolished the pro
      apoptotic effects of TGF-beta on post-activated T cells, thus demonstrating that
      TGF-beta increases the cytokine-dependence of T cells for survival. We propose a
      novel role for TGF-beta in the suppression of inflammation by promoting the
      elimination of post-activated T cells once the initiating stimulus has been
      resolved.

PMID- 11298828
TI  - The developing human immune system: T-cell receptor repertoire of children and
      young adults shows a wide discrepancy in the frequency of persistent oligoclonal
      T-cell expansions.
AB  - While the T-cell receptor (TCR) repertoire of the newborn is highly diverse, a
      gradual alteration in diversity of the expressed TCR repertoire, in particular
      the oligoclonality of CD8+ T cells, occurs with increasing age. The timing of the
      initiation of this process is unknown. These changes are associated with an
      accumulation of T-cell expansions, thought to be in response to chronic antigen
      stimulation, frequently by persistent viruses such as Epstein-Barr virus (EBV)
      and cytomegalovirus (CMV). Using reverse transcription-polymerase chain reaction
      heteroduplex analysis we have characterized the TCR expression of CD4 and CD8
      cells from healthy young children and adults in order to delineate the age range
      at which these oligoclonal populations appear. We demonstrate that considerable
      oligoclonality can occur, even in healthy young children, and also that these
      expanded clonotypes persist. These are shown by heteroduplex to be exclusively
      within the CD28- subpopulation. The presence of such oligoclonal expansions
      correlates closely with the percentage of CD8+ cells that have the CD28-
      phenotype. However, we also show that control of chronic infection with EBV or
      CMV may coexist with a highly diverse, polyclonal TCR repertoire well into
      adulthood. These studies suggest that many factors affect the overall regulation
      of clone size in response to chronic antigens during the development of the
      immune system.

PMID- 11298830
TI  - Local versus systemic control of numbers of endometrial T cells during pregnancy
      in sheep.
AB  - Pregnancy in sheep is associated with changes in numbers of specific T-lymphocyte
      populations in the uterine endometrium. These changes probably contribute to
      evasion by the conceptus of maternal immunological rejection and indicate a
      possible role for T cells in placental growth, parturition and post-parturient
      uterine defence against infection. The purpose of the present experiment was to
      evaluate the relative importance of systemic signals (i.e. those present
      throughout the uterus or from the circulation, including conceptus hormones
      secreted into the maternal blood) versus locally acting conceptus signals for
      regulating changes in numbers of endometrial lymphocytes during pregnancy. The
      approach taken was to surgically confine pregnancy to one uterine horn and
      compare differences in lymphocyte numbers between the two uterine horns as well
      as between both horns of pregnant ewes with those of ovariectomized ewes. As
      compared with ovariectomized ewes, there was a decline in numbers of CD45R+
      lymphocytes within glandular epithelium and an increase in gammadelta T-cell
      number within the luminal epithelium. These changes occurred in both the pregnant
      and non-pregnant uterine horns of unilaterally pregnant ewes. Moreover, there
      were no significant differences in lymphocyte numbers between the two uterine
      horns of unilaterally pregnant ewes. Expression of CD25 was absent in tissues
      from both uterine horns. In conclusion, changes in numbers of endometrial
      lymphocytes during pregnancy, rather than due to locally acting signals of
      conceptus origin, are the result of hormonal signals of maternal or conceptus
      origin that either act directly on endometrial lymphocytes or stimulate the
      uterine endometrium to induce synthesis of regulatory molecules that affect
      lymphocyte dynamics.

PMID- 11298831
TI  - Interleukin (IL)-18 induces Langerhans cell migration by a tumour necrosis factor
      alpha- and IL-1beta-dependent mechanism.
AB  - Following skin sensitization a proportion of epidermal Langerhans cells (LC) are
      stimulated to leave the skin and to migrate, via afferent lymphatics, to draining
      lymph nodes where they accumulate as immunostimulatory dendritic cells (DC). It
      has been demonstrated previously that tumour necrosis factor-alpha (TNF-alpha),
      an inducible product of epidermal keratinocytes, and interleukin (IL)-1beta,
      produced exclusively by LC in murine epidermis, provide important signals for the
      initiation of this response. Recently, it has been demonstrated that IL-18, a
      cytokine produced by both LC and keratinocytes within the epidermis, may also
      participate in immune responses induced following skin sensitization. In the
      present investigations, the ability of IL-18 to contribute to the regulation of
      LC migration and the accumulation of DC in draining lymph nodes has been
      examined. It was found that, like IL-1beta, IL-18 administered intradermally to
      mice resulted in a significant reduction in epidermal major histocompatibility
      complex (MHC) class II+ LC densities and a marked increase in lymph node DC
      numbers. Using neutralizing anti-TNF-alpha and blocking anti-type I IL-1 receptor
      (IL-1RI) antibodies, it was shown also that the induction by IL-18 of both LC
      mobilization and DC accumulation in regional lymph nodes was dependent upon
      availability of TNF-alpha and the integrity of IL-1RI signalling. Furthermore,
      using IL-1beta converting enzyme (caspase-1) knockout mice, IL-18-induced LC
      migration was found to have a mandatory requirement for active IL-1beta.
      Importantly, not only was IL-18 able to contribute to the regulation of LC
      migration, it was found to be essential for the manifestation of these processes
      in response to topical sensitization with the contact allergen oxazolone.

PMID- 11298832
TI  - Interleukin-10 induces macrophage apoptosis and expression of CD16 (FcgammaRIII)
      whose engagement blocks the cell death programme and facilitates differentiation.
AB  - The development of monocytes into macrophages is regulated by helper T cells (Th)
      cells and, vice versa, the differentiation of Th cells into Th1 and Th2 is
      regulated by macrophages. Herein we examined the role of the Th2 cytokine,
      interleukin-10 (IL-10), on the development of macrophages. IL-10 is known to
      block the expression of antigen-presenting major histocompatibility complex (MHC)
      II and of costimulatory B7 molecules but it induces the expression of FcRs,
      especially the FcgammaRIII (CD16). The expression of CD16 enables the macrophage
      to carry out antibody-dependent cell-mediated cytotoxicity (ADCC) functions.
      However, this differentiation step is largely undercut by the capacity of IL-10
      to induce macrophage apoptosis before the process of differentiation ensues. We
      found that the negative effect of IL-10 on the survival of macrophages is
      reversed in an environment that contains immunoglobulin G (IgG). IgG, especially
      when immune complexed with antigen, stimulates CD16 to transmit survival signals
      in macrophages which enable them to complete the differentiation process into
      CD16+ cells. Thus, IL-10 suppresses macrophage accumulation in healthy tissues
      where IgG is absent, and facilitates macrophage accumulation and differentiation
      in tissues that contain IgG, for example inflamed tissues or tissues that present
      autoreactive antibodies.

PMID- 11298833
TI  - Isolation, cloning and functional characterization of porcine mannose-binding
      lectin.
AB  - Binding of mannose-binding lectin (MBL), a C-type lectin, and its associated
      serine proteases, MASP-1 and MASP-2, to cell surface carbohydrates activates the
      lectin complement pathway. As MBL plays an important role in innate immunity, it
      has been cloned and characterized in several species. While the pig may be used
      as a source of organs/tissues for xenotransplantation, little is known about its
      MBL, thus, we report the isolation of three monomeric forms of MBL from porcine
      serum. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Coomassie
      staining of reduced porcine MBL revealed the presence of three monomeric forms
      with approximate molecular masses of 30 000, 32 000 and 34 000. Protein
      sequencing identified these monomeric forms as one single protein, suggesting
      post-translational modification. Western blot analysis demonstrated the cross
      reactivity of anti-human MBL polyclonal antibody with porcine MBL. A full-length
      porcine liver MBL cDNA was isolated and the predicted amino acid sequence
      exhibited 64.9% identity with human MBL and 50.2% and 56.7% identity with rat A
      and C MBL, respectively. Furthermore, Northern blot analysis demonstrated the
      presence of a single ( approximately 1.4-1.6 kilobase pair) transcript in porcine
      liver. Addition of purified porcine MBL to MBL-deficient human sera augmented N
      acetylglucosamine inhibitable C3 deposition to mannan-coated plates in a dose
      dependent manner. Taken together, these data demonstrate that porcine and human
      MBL are highly conserved, sharing structural and functional characteristics.

PMID- 11298834
TI  - Immunization onto bare skin with heat-labile enterotoxin of Escherichia coli
      enhances immune responses to coadministered protein and peptide antigens and
      protects mice against lethal toxin challenge.
AB  - In this study, the potential of the bare skin as a non-invasive route for
      vaccination was examined. Following application of heat-labile enterotoxin (LT)
      of Escherichia coli onto bare skin of BALB/c mice, strong serum anti-LT antibody
      responses were observed, and mucosal immunoglobulin A (IgA) and IgG antibodies
      were measured in vagina washes. In addition, LT enhanced the serum and mucosal
      antibody and proliferative T-cell responses to the model protein antigen beta
      galactosidase (beta-gal) when coadministered onto bare skin, highlighting its
      potential to exert an adjuvant effect. When a peptide representing a T-helper
      epitope (aa 307-319) from the haemagglutinin of influenza virus was applied onto
      bare skin with LT or cholera toxin (CT), it primed effectively peptide- and virus
      specific T cells, as measured in vitro by the interleukin-2 (IL-2) secretion
      assay. LT was shown to be as immunogenic as CT. Binding activity to GM1
      gangliosides was essential for effective induction of anti-CT serum and mucosal
      antibody responses. Finally, mice immunized onto bare skin with LT were protected
      against intraperitoneal challenge with a lethal dose of the homologous toxin.
      These findings give further support to a growing body of evidence on the
      potential of skin as a non-invasive route for vaccine delivery. This immunization
      strategy might be advantageous for vaccination programmes in Third World
      countries, because administration by this route is simple, painless and
      economical.

PMID- 11298835
TI  - Reduced herpes simplex virus type 1 latency in Flt-3 ligand-treated mice is
      associated with enhanced numbers of natural killer and dendritic cells.
AB  - We have investigated the effect of Flt-3 ligand (Flt-3L) on the resistance to
      herpes simplex virus type-1 (HSV-1) infection in BALB/c mice which are normally
      highly susceptible to challenge with this virus. We have confirmed data by others
      that in vivo treatment with Flt-3L causes an increase in dendritic cells (DC) and
      natural killer (NK) cells in lymphoid tissue. Increasing doses of Flt-3L caused a
      corresponding increase in liver and spleen CD11c+ DC which were increased up to
      20-fold compared with control levels. A significant expansion of NK cells was
      seen in the spleen of Flt-3L-treated mice where the number of DX5+ cells was
      increased by up to fivefold. We subsequently tested the hypothesis that Flt-3L
      treatment, at the time of viral infection, might lead to enhanced immunity and
      protection against viral pathogenesis. Two murine models of HSV-1 (SC16)
      infection were used. In the first model, mice were injected with Flt-3L daily for
      9 days. Control mice received mouse serum albumin (MSA). On day 7 of the Flt-3L
      treatment 106 plaque-forming units (PFU) of SC16 was inoculated into the ear
      pinna. Flt-3L treatment significantly reduced mortality following virus
      inoculation, with 80% survivors in this group compared with 20% survivors in the
      MSA-treated group. In the second model, Flt-3L-treated mice were scarified with
      104 PFU of SC16. In this case there was 60% survival in the Flt-3L-treated group
      of mice compared with 10% survival in the MSA-treated group. Assessment by in
      situ hybridization for latency-associated transcripts showed that Flt-3L
      treatment reduced the amount of latent virus within infected neurons. These
      studies show that in vivo treatment with Flt-3L results in protection against
      challenge with live HSV-1, which may be a consequence of enhanced numbers of DC
      and/or NK.

PMID- 11298836
TI  - Complement activation by apoptotic endothelial cells following
      hypoxia/reoxygenation.
AB  - Reperfusion of ischaemic tissue initiates an inflammatory reaction that increases
      tissue injury. Complement activation at the endothelium contributes to this
      inflammation. This study investigated the mechanism of complement activation
      following reoxygenation of hypoxic human umbilical vein endothelial cells (HUVEC)
      as a model for complement activation observed on endothelium in reperfused
      ischaemic tissue. HUVEC cultured in 1% oxygen followed by reoxygenation activated
      the classical complement pathway resulting in C3 deposition. There was an
      increase in apoptotic cells in these cultures that was demonstrated by binding of
      fluorescein isothiocyanate-Annexin V and staining for hypodiploid nuclei. To
      determine if apoptotic HUVEC activate complement, uniformly apoptotic cells were
      produced by serum and growth factor deprivation. These cells, but not the control
      HUVEC, activated the classical complement pathway in the absence of antibody or
      other serum factors. To determine if apoptotic cells in the reoxygenated cultures
      were activating complement, fluorescent analysis was done. Annexin V binding and
      C3d deposition on cells from reoxygenated cultures showed complete concordance on
      the subpopulation of apoptotic cells. In addition, complement activation
      following reoxygenation of HUVEC was eliminated by treatment of the cultures with
      a caspase inhibitor during reoxygenation. These results suggest that oxidative
      damage to endothelial cells during reoxygenation initiates apoptosis with
      exposure of phosphatidylserine. Apoptotic cells directly activate the classical
      pathway of complement by binding C1. Activation of complement at the endothelium
      may contribute to the inflammatory response as well as clearance and repair.

PMID- 11298837
TI  - Complement-mediated lipopolysaccharide release and outer membrane damage in
      Escherichia coli J5: requirement for C9.
AB  - Lipopolysaccharides (LPS) are major antigenic components of the outer membrane of
      Gram-negative bacteria and can stimulate activation of the complement system.
      Such activation leads to formation of the complement membrane attack complex
      (MAC) on the cell walls, LPS release and, in serum-sensitive strains, to cell
      death. In this study, Escherichia coli J5 strains, which incorporate exogenous
      galactose exclusively into LPS, were used to generate target strains with
      different LPS chemotypes, and the LPS of the strains was labelled with tritium
      (3H-LPS). The ability of normal human serum (NHS) and human complement-deficient
      sera to release LPS was subsequently monitored. NHS-induced release of 64-95.7%
      of 3H-LPS within 30 min; overall, no significant difference was observed between
      release of LPS from E. coli J5 strains with different LPS chemotypes. In
      functional assays, maximum LPS release had occurred by 30 min and before maximum
      bacterial killing. Electron microscopy revealed NHS-induced outer-membrane
      disruption in the form of blebs at 15 min; at this time-point the inner membrane
      remained intact. Background LPS release and no bactericidal activity were
      detected in heat-inactivated serum or human sera deficient in C6, C7 or C8. The
      C9-deficient (C9D) serum had low bactericidal activity and failed to induce LPS
      release; however, addition of purified human C9 reconstituted its ability to
      release LPS. This study demonstrated the need for functional C9 molecules for LPS
      releasing activities in serum-sensitive E. coli J5 strains.

PMID- 11298838
TI  - Modulation of delayed-type hypersensitivity during the time course of immune
      response to a protein antigen.
AB  - Delayed-type hypersensitivity reactions elicited in the footpad of ovalbumin
      sensitized mice after challenge with aggregated ovalbumin on day 4 or 8 of
      immunization are distinct. The former was characterized by a dense mononuclear
      infiltrate and, macroscopically, the reaction peaked at 48 hr after antigen
      challenge; the latter was preceded by immediate-type reactions, reached the
      maximum at 24 hr and faded drastically later. Histologically, oedema and a mixed
      granulocytic-lymphocytic infiltrate was found at this time-point. Immunoglobulin
      G1 (IgG1), IgG2a and IgE antibodies were detected only in plasma obtained after 8
      days of immunization. Regarding the cytokines produced by draining lymph node
      cells after in vitro restimulation, interleukin-4 (IL-4) and IL-10 were
      predominant after 4 days and interferon-gamma and IL-2 after 8 days of
      immunization. These two types of delayed-type hypersensitivity (DTH) were used to
      study the influence of antibody-mediated responses on the inductive and effector
      phases of cell-mediated immunity. The effector phase of DTH was not affected by
      immediate-type reactions, as abrogation of these reactions by mediators'
      antagonists on day 8 or induction of passive reactions by transfer of immune
      serum on day 4 did not change the extent or kinetics of either type of DTH. Only
      transfer, before immunization, of whole or T-cell-enriched spleen cells, but not
      sera, from hyperimmunized donors (high antibody producers) abolished the
      induction of pure DTH in 4-day immunized recipient mice and changed their
      cytokine profile to a T helper 2 type. These results indicate that in a non
      polarized immune response to a protein antigen there is initially a bias towards
      cell-mediated immunity, which is gradually dampened by the development of
      antibody-mediated immunity.

PMID- 11298839
TI  - Comparison between computerized slow-stage and static liquid nitrogen vapour
      freezing methods with respect to the deleterious effect on chromatin and
      morphology of spermatozoa from fertile and subfertile men.
AB  - The purpose of this study was to determine the negative effects (cryodamage) on
      human spermatozoa after freeze-thawing and to determine whether freeze-thawing of
      spermatozoa with a programmed slow freezer is better than freezing with liquid
      nitrogen vapour (rapid freezing) with regard to alterations in sperm chromatin
      and morphology in semen from fertile (donor) and subfertile, IVF/ICSI, patients.
      Ninety-five semen samples were obtained either from patients attending our IVF
      unit for treatment (n=34) or from donors (n=25) with proven fertility and normal
      sperm quality according to WHO guidelines. Each semen sample was divided into two
      parts after liquefaction and addition of the cryoprotectant. The first part was
      frozen using a programmed biological freezer and the second part was frozen by
      means of liquid nitrogen vapour. Smears were made before the freezing and after
      the thawing procedure to assess morphology (strict criteria) and chromatin
      condensation (Acridine Orange test). The mean percentage of chromatin condensed
      spermatozoa in the samples from donors (control group) was 92.4 +/- 8.4% before
      freezing and this decreased significantly (p < 0.0001) to 88.7 +/- 11.2% after
      freeze-thawing with the computerized slow-stage freezer and to 87.2 +/- 12.3%
      after using static liquid nitrogen vapour (p < 0.001). The corresponding values
      for semen obtained from patients was 78.9 +/- 10.3% before freezing which
      decreased to 70.7 +/- 10.8 and 68.5 +/- 14.8%, respectively (p < 0.001). On the
      other hand, the mean percentage of normal sperm morphology in the control group
      decreased from 26.3 +/- 7.5% before freezing to 22.1 +/- 6.4% (p < 0.0001) after
      thawing with the computerized slow-stage freezer and to 22.2 +/- 6.6% (p <
      0.0001) after the use of static liquid nitrogen vapour. In the patient group, the
      mean percentage of normal morphology decreased from 11.7 +/- 6.1% after freezing
      with the biological freezer to 9.3 +/- 5.6% and to 8.0 +/- 4.9% after freezing
      with static liquid nitrogen vapour. This study demonstrates that chromatin
      packaging and morphology of human spermatozoa decrease significantly after the
      freeze-thawing procedure, not only after the use of static liquid nitrogen vapour
      but also after the use of a computerized slow-stage freezer. However, the
      chromatin of semen samples with normal semen parameters (donor sperm) withstand
      the freeze-thaw injury better than those with low quality semen samples.
      Therefore, the computerized slow stage freezer could be recommended for freezing
      of human spermatozoa, especially for subnormal semen samples, for example, ICSI
      and ICSI/TESE candidates and from patients with testicular tumours or Hodgkin's
      disease, in order to avoid further damage to the sperm chromatin structure.

PMID- 11298840
TI  - Genetic, andrological and clinical characteristics of patients with congenital
      bilateral absence of the vas deferens.
AB  - The possibility of retrieving spermatozoa from the epididymis allows patients
      with congenital bilateral absence of the vas deferens (CBAVD) to father a child
      by means of assisted reproduction techniques. This has, however, increased the
      chance of transmitting a mutated allele of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene which increases the risk of generating
      offspring with cystic fibrosis (CF). Because of the increased heterogeneity of
      the CFTR locus, the study of a discrete number of mutations, as usually carried
      out in a diagnostic work-up, is unable to ascertain the presence of a mutation in
      a relatively high proportion of the patients screened. In an attempt to increase
      the chance of detecting the presence of CFTR gene abnormalities, 37 patients with
      CBAVD and one patient with congenital unilateral agenesis of the vas deferens
      (CUAVD) underwent an enlarged diagnostic protocol, which included screening for
      the most expected mutations of the CFTR gene in our population, evaluation of the
      five thymidine (5T) allelic variant, sweat test, respiratory function tests,
      evaluation of steatocrit, and an accurate evaluation of the history of the
      patient to search for symptoms commonly found in patients with CF. A single CFTR
      gene mutation was found in 18 patients (48.6%) with CBAVD and in the patient with
      CUAVD. The most frequent mutation observed was the Delta F508. Eleven patients
      (45.8%) had the 5T variant and in five of them it was not associated with any
      detectable mutation of the CFTR gene. Two female partners were found to be
      carriers of a mutation, whereas 5 (18.5%) had the 5T variant. As many as 71% of
      CBVAD patients had the simultaneous presence of at least two signs and/or
      symptoms suggestive of CF, albeit they were of mild intensity and the patients
      felt fit and healthy. In conclusion, these results suggested that some patients
      with CBAVD without CFTR gene mutation or 5T variant, even when their sweat test
      is negative, may show clinical suspicion of carrying a CFTR gene mutation and
      therefore are at risk of generating children affected by CF if the partner
      carries a mutation as well. The screening for mutations and a careful clinical
      examination may contribute to better identification of patients with CFTR-related
      CBAVD.

PMID- 11298841
TI  - Changes in binding of iodomelatonin to membranes of Leydig cells and
      steroidogenesis after prolonged in vitro exposure to melatonin.
AB  - The aim of the present study was to investigate the effects of prolonged exposure
      to melatonin (MLT) on the binding of iodomelatonin to membranes of rat Leydig
      cells and the subsequent modulation of testosterone and cyclic adenocine
      monophosphate (cAMP) secretion from these cells by MLT itself. Leydig cells were
      Percoll-purified from adult rats and cultured in vitro with MLT (1--100 nmol/L)
      for 16 h. Binding assays with 2(125I)iodomelatonin were then performed; moreover,
      testosterone and cAMP secretion during an acute challenge with lutenizing hormone
      (LH) (20 mIU/mL for 3 h) was assayed by RIA. As a result of prolonged MLT
      administration, a decrease in maximum binding density (Bmax) and equilibrium
      dissociation constant (Kd) of the binding of 2(125I)iodomelatonin to purified
      cell membranes was noted. Higher testosterone and cAMP secretion during LH
      challenge were recorded in cells pre-incubated with MLT; notwithstanding, the
      inhibitory effect of acutely administered MLT on LH-challenged secretions was not
      only retained but also reinforced, as the IC50 was 30% lower in cells pre-treated
      with the higher concentration of MLT (100 nM). Cycloheximide administration (10
      microg/mL for 16 h) did not prevent hyper-sensitization to LH challenge or to
      acute MLT administration on LH challenge. Pertussis toxin (180 ng/mL for 16 h)
      prevented hyper-sensitization to LH, but not to acutely administered MLT.
      Forskolin (10 nmol/L) administration abolished either phenomena. In conclusion,
      prolonged exposure to MLT modulates the secretion of testosterone by cultured rat
      Leydig cells. Although MLT receptors were reduced, hyper-sensitization to LH
      challenge and to acutely administered MLT on LH challenge were observed with the
      higher concentration of MLT. Reduction in intracellular cAMP as a result of
      prolonged administration of MLT, could be the primary cause of both phenomena. On
      the one hand, reduced cAMP could start re-arrangement of the G-proteins and thus
      LH-dependent adenylate cyclase sensitization. On the other hand, reduced cAMP
      could render the Leydig cells more responsive to MLT itself through a mechanism
      which does not involve G-protein re-arrangement.

PMID- 11298842
TI  - Imprinting analysis in spermatozoa prepared for intracytoplasmic sperm injection
      (ICSI).
AB  - Genetic imprinting is a mechanism of gene regulation by which only one of the
      parental copies of a gene is expressed. This process is mediated by the
      methylation of DNA. As spermatozoa represent exclusively the paternal
      contribution to a future individual, they are expected to carry the paternal
      imprint only. For intracytoplasmic sperm injection (ICSI), spermatozoa mostly
      have to be selected from samples with pathological semen parameters. Correct
      establishment of the paternal imprint in these spermatozoa has not yet been
      demonstrated. In the present study, imprinting analysis was undertaken using DNA
      extracted from spermatozoa from men with normal semen analysis (group A: n=30
      patients) and from men with an abnormal sperm count (B: n=30 patients with 5--20
      million spermatozoa/mL and C: n=30 patients with < or =5 million spermatozoa/mL)
      from the ICSI program. It was performed using firstly a conventional methylation
      specific polymerase-chain-reaction (M-PCR) and secondly a more sensitive modified
      hemi-nested M-PCR technique. In addition, a single cell PCR was performed on a
      total of 88 single spermatozoa (collected from nine males) and on 25 leucocytes
      (control group). With the conventional M-PCR, exclusively paternal imprints were
      found in all groups. Using the more sensitive hemi-nested M-PCR, additional
      maternal imprints were found in 63% of the samples in A, 57% in B and 60% in C.
      In the single cell PCR, exclusively paternal imprints were detected. Because of
      the very small amount of DNA (3 pg), a complete amplification failure occurred in
      43% of spermatozoa. The correct paternal and maternal imprints were found in 56%
      of the analysed leucocytes (complete amplification failure in the other 44%). In
      conclusion, ejaculated spermatozoa from males with medium or high-grade semen
      pathology proved to have the same imprinting status as those from males with
      normal semen parameters. As the additional maternal imprints were never found at
      the single cell level, they were classified as contamination by diploid cells
      such as leucocytes or immature germ cells in the processed and purified semen
      samples, which can be detected by a more sensitive PCR method in contrast to the
      conventional standard PCR.

PMID- 11298843
TI  - Differential patterns of inhibin secretion in response to gonadotrophin
      stimulation in normal men.
AB  - Inhibin B is produced by the testis, and its constituent alpha and beta B
      subunits have been localized immunohistochemically to Leydig as well as Sertoli
      cells in both rodent and human testes. Whether Leydig cells contribute to
      circulating inhibin B concentrations, however, is uncertain. We have investigated
      this by selectively stimulating Leydig and Sertoli cells with hCG and FSH,
      respectively. The study was a randomized crossover trial, investigating responses
      to 225 IU recombinant FSH or 3000 IU hCG administered s/c 4-6 weeks apart. Ten
      normal men were recruited to participate. Blood was taken twice before treatment
      and after 8, 24, 48, 72 and 96 h. Serum was assayed for FSH, LH and testosterone
      by radioimmunoassay (RIA); inhibin B and pro-alpha C inhibin forms by ELISA.
      Administration of hCG, but not FSH, caused a rapid increase in blood testosterone
      levels, which reached a maximum after 72 h (22.2 +/- 2.7-50.1 +/- 4.5 nmol/L, p <
      0.001). Inhibin B concentrations in blood were unchanged following either
      treatment. Conversely, pro-alpha C concentrations increased following both
      treatments. FSH administration resulted in a gradual increase in pro-alpha C
      concentrations (369 +/- 18 pg/mL pre-treatment to 453 +/- 33 pg/mL after 96 h,
      p=0.013). Administration of hCG resulted in a more rapid response, with pro-alpha
      C concentrations rising from 384 +/- 23 pg/mL pre-treatment to a peak at 48 h of
      535 +/- 45 pg/mL (p=0.007). This response was more rapid than that of
      testosterone. These results demonstrate that adult human Leydig, as well as
      Sertoli, cells secrete inhibin alpha subunit in response to gonadotrophin
      stimulation but provide no evidence for the secretion of inhibin B from Leydig
      cells. The lack of change in inhibin B secretion in response to FSH suggests that
      more prolonged or intense stimulation of Sertoli cells may be required for
      secretion of the dimeric form.

PMID- 11298845
TI  - Value of the hamster oocyte test and computerised measurements of sperm motility
      in predicting if four or more viable embryos will be obtained in an IVF cycle.
AB  - The experimental group consisted of men from 81 couples waiting for in vitro
      fertilization (IVF), about half of whom had sperm dysfunction defined by a
      negative post-coital test. A diagnostic semen sample was subjected to a hamster
      oocyte penetration test (HOPT) after stimulation of the acrosome reaction with
      A23187 +/- pentoxifylline and to computerized sperm motility measurements (CASA)
      as well as conventional semen analysis according to the WHO protocol. Logistic
      regression was used to identify parameters that predicted the probability of
      achieving four or more viable embryos at IVF among the 65 couples from whom four
      or more oocytes were collected. The number of oocytes available and whether the
      woman had previously been pregnant (ever pregnant) were important factors but
      once these had been taken into account a number of sperm parameters had
      additional predictive power. The most useful of these were the percentage sperm
      static (CASA) or the percent sperm progressively motile (conventional semen
      analysis) in the Percoll preparation. A model incorporating the number of oocytes
      collected, ever pregnant and percentage sperm static achieved 85% correct
      prediction of outcome in the experimental dataset but only 62% correct prediction
      in an independent set of 280 IVF cycles. The percentage of hamster oocytes
      penetrated was a significant predictor but had no advantage over simple motility
      measurements. The results illustrate the difficulty of basing a prognosis for
      achieving satisfactory fertilization in IVF on the properties of spermatozoa.

PMID- 11298844
TI  - Prediction of unexpectedly poor fertilization and pregnancy outcome using the
      strict criteria for sperm morphology before and after sperm separation in IVF-ET.
AB  - This study was performed to investigate if unexpectedly poor fertilization and in
      vitro fertilization (IVF) outcome could be predicted using sperm morphology as
      diagnosed by the strict criteria. Sperm morphology was assessed in 137 IVF-ET
      cycles with at least three oocytes collected. The lowest amount of normal forms
      was 5% in 137 samples, indicating there were no patients belonging to 'poor
      prognosis' (<5% normal forms). Treatment using intracytoplasmic sperm injection
      (ICSI) was also excluded. Before sperm separation by the swim-up method, sperm
      morphology demonstrated a significant correlation with the fertilization rate (p
      < 0.0001). The fertilization rate (80.5%) in 110 'normal' samples (>14% normal
      forms) was significantly higher (p < 0.01) than that (55.4%) in 27 samples with
      'good prognosis' (those with 5--14% normal forms). No embryo was available for
      transfer (ET) in 4 (3.6%) of 110 'normal' cycles and in 3 (11.1%) of 27 'good
      prognosis' cycles (not significant). Fresh ET was intentionally cancelled to
      avoid severe ovarian hyperstimulation syndrome (OHSS) in six of 110 'normal'
      cycles as well as in one of 27 'good prognosis' cycles. The pregnancy rate per ET
      was 31.0% (31/100) in the former group, while it was 26.1% (6/23) in the latter
      group. There was no difference between the two groups. In the post swim-up
      evaluation of sperm characteristics, morphology was significantly correlated with
      the fertilization rate in IVF-ET (p < 0.05) while other sperm parameters were
      not. When the cut off level for the post swim-up sperm morphology was set at 25%,
      there was a significant difference in the fertilization rates between patients
      (78.6%) with post-swim-up >25% and those (55.0%) with post-swim-up < or =25% (p <
      0.01). Taken together, a relative indication for ICSI using sperm morphology
      before and after swim-up was established. Category A includes < or =14% normal
      forms in the ejaculate and post-swim-up < or =25%, while Category B includes < or
      =14% in the ejaculate and post-swim-up >25%. There was a significant difference
      in the fertilization rates between patients (47.2%) in Category A and those
      (60.2%) in Category B (p < 0.05). The clinical pregnancy rate was 11.1% for
      patients in Category A compared with 35.7% for patients in Category B. However,
      there was no significant difference between the two categories. These results
      indicate that the strict criteria provide a reliable estimation of the
      fertilizing ability of human spermatozoa. ICSI might be considered in Category A
      patients to avoid poor fertilization and pregnancy outcome.

PMID- 11298846
TI  - Reassessment of sperm morphology of archival semen smears from the period 1980-
      1994.
AB  - Several reports have suggested that sperm counts of normal men have declined in
      many geographical regions during the last decades. Deterioration of sperm
      morphology has also been reported in some studies covering long sample collecting
      periods. The original semen analysis data of our semen laboratory from the period
      1980--1994 showed a significant decline in the proportion of spermatozoa with
      normal morphology. The finding was, however, questioned because of changes in
      sperm morphology assessment criteria during the study period. In the present
      study 1745 smears were re-analysed to cover evenly the whole study period. The
      samples were examined in random order by using strict assessment criteria.
      Multiple linear regression analysis of the re-analysed data showed no effect of
      the year of sample delivery on sperm morphology between the years 1980 and 1994.
      However, there was a significant decline in the proportion of normal spermatozoa
      with later year of men's birth.

PMID- 11298847
TI  - Prediction of diabetes with body mass index, oral glucose tolerance test and
      islet cell autoantibodies in a regional population.
AB  - OBJECTIVE: Our aim was to test the hypothesis that a combination of markers for
      Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2
      diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would
      predict clinical diabetes in a regional population. DESIGN: A population-based
      follow-up cohort study. SETTING: Participants visited the primary health care
      centre in Lycksele, Sweden in 1988-92. PARTICIPANTS: A cohort of 2278 subjects
      (M/F 1149/1129) who were studied at follow-up in 1998. At base line there were
      2314 subjects (M/F 1167/1147) who participated in the Vasterbotten Intervention
      Program on their birthday when turning either 30, 40, 50 or 60 years of age. Main
      outcome measurements. A clinically diagnosed diabetes at follow-up when the
      medical records were reviewed for diagnosis of diabetes. At base line, the
      participants were subjected to a standard OGTT and their BMI determined along
      with the autoantibodies. RESULTS: At follow-up, 42/2278 (1.8%, 95% CI 1.2-2.3)
      (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with
      Type 2 and one with Type 1 diabetes. There was no significant relation between
      autoantibody levels at base line and diabetes at follow-up. Stepwise multiple
      logistic regression showed that the odds ratio for developing diabetes was 10.8
      (95% CI 6.3-18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared
      with 7.8 (95% CI 4.8-12.6) in the fourth quartile of 2-h plasma glucose (>7.5
      mmol L(-1)) and 7.2 (95% CI 4.8-11.4) in the fourth quartile of the fasting
      plasma glucose (>5.6 mmol L(-1)). CONCLUSION: Islet cell autoantibodies did not
      predict diabetes at follow-up. BMI measured at base line was as effective as 2-h
      plasma glucose and fasting plasma glucose to predict diabetes in this adult
      population.

PMID- 11298848
TI  - Specific T-cell receptor usage with cytokinemia in Henoch-Schonlein purpura
      nephritis associated with Staphylococcus aureus infection.
AB  - OBJECTIVES: We sought to evaluate the mechanism of Henoch-Schonlein purpura
      nephritis (HSPN) associated with Staphylococcus aureus (S. aureus) infection.
      DESIGN: We evaluated six male patients with HSPN associated with S. aureus
      infection. Routine laboratory examinations, bacteriological examination,
      histological examination, and analysis of serum cytokine levels were performed in
      all cases. In addition, peripheral blood mononuclear cells (PBMC) obtained from
      the six patients and 45 normal individuals were stained with labelled-monoclonal
      antibodies against six variable parts of the beta-chain (Vbeta) of the T-cell
      receptor (TCR), and stained cells were analysed by flow cytometry. RESULTS:
      Patients with HSPN associated with S. aureus infection showed features of the
      nephrotic syndrome with rapidly progressive glomerulonephritis, as well as
      varying degrees of mesangial proliferative glomerulonephritis with crescent
      formation. Serological examination showed elevated levels of serum IgA and IgG as
      well as immune complexes after the onset of infection. The percentage of Vbeta
      (5.2 + 5.3) and Vbeta 8-positive cells in patients with HSPN were significantly
      higher than in normal individuals; moreover, specific TCR-Vbeta usage was not
      observed in patients with HSPN whose S. aureus infection had improved. Serum
      levels of IL-1beta, IL-2, IL-6, IL-8 and TNF-alpha in patients with HSPN were
      significantly higher than in normal individuals, and normalized at the healing
      stage of S. aureus infection. CONCLUSION: Conventional antigens and/or
      staphylococcal enterotoxins originated from S. aureus might have been involved in
      the pathogenesis of HSPN in the present cohort. Therefore, steroid or other
      immunosuppressive therapies could not be utilized despite the high activity of
      glomerulonephritis, and as a result the prognoses of these cases of HSPN were
      serious.

PMID- 11298849
TI  - Comparison of echocardiography and radionuclide ventriculography in the follow-up
      of left ventricular systolic function in adult lymphoma patients during
      doxorubicin therapy.
AB  - OBJECTIVES: To compare echocardiography (ECHO) and radionuclide ventriculography
      (RVG) in the monitoring of left ventricular systolic function during doxorubicin
      therapy in adult lymphoma patients. DESIGN: Prospective study. SETTINGS:
      University hospital. SUBJECTS: A total of 28 adult patients who received
      doxorubicin to a cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: ECHO
      and RVG were performed at baseline and after cumulative doxorubicin doses of 200,
      400 and 500 mg m(-2). RESULTS: At baseline, the mean (+/-SE) left ventricular
      ejection fractions (LVEF) were 58 +/- 1.3, 71 +/- 1.8 and 58 +/- 1.7% as
      determined by RVG, M-mode ECHO and two-dimensional (2D) ECHO, respectively. After
      the cumulative doxorubicin dose of 500 mg m(-2) LVEF decreased to 49.6 +/- 1.7%
      (RVG) (P < 0.001), 62 +/- 1.6% (M-mode) (P=0.006) and 52.5 +/- 1.3% (2D ECHO)
      (P=0.036). Although a significant correlation between LVEF determined by RVG and
      M-mode ECHO (r=0.615, P=0.002) and a trend between RVG and 2D ECHO (r=0.364,
      P=0.096) were observed, there were substantial differences in the results of
      individual patients. In the agreement analysis using the method of Bland and
      Altman there was a mean difference of 12% units with the upper limit of agreement
      +26% units and the lower limit of agreement -2.1% units for LVEF determinations
      with M-mode ECHO and RVG, and a mean difference of 3.3% units with upper and
      lower limits of agreement +19.6 and -13.1% units for LVEF determinations with 2D
      ECHO and RVG, respectively. CONCLUSION: We found only a moderate agreement
      between left ventricular systolic function determined by ECHO and RVG methods.
      Thus, in the follow-up of left ventricular function in adult patients during
      doxorubicin therapy, the guidelines based on LVEF measurement by RVG cannot be
      applied to ECHO. Consequently, RVG remains the method of choice in this context.

PMID- 11298850
TI  - Multiple risk intervention trial in high risk hypertensive men: comparison of
      ultrasound intima-media thickness and clinical outcome during 6 years of follow
      up.
AB  - OBJECTIVES: The objective was to analyse whether a favourable change in risk
      factors, caused by a comprehensive risk factor modification programme, affected
      intima-media thickness (IMT) in the common carotid artery, and whether any such
      change was associated with a change in cardiovascular events during a 6-year
      follow-up. DESIGN: Patients were randomized 1 : 1 to special intervention or
      usual care. SETTING: Hypertension Unit at university hospital. SUBJECTS: A total
      of 164 patients were randomized. Inclusion criteria were male, aged 50-72 years
      (at randomization) and one or more of the following: Serum cholesterol level >
      6.5 mmol L(-1), smoking or diabetes mellitus. All patients were prescribed
      antihypertensive treatment since many years. In 142 men good quality ultrasound
      recording of the common carotid IMT were achieved at baseline, 119 were re
      examined after 3.3 years, and 97 patients were available for examination after
      mean follow-up time of 6.2 years. Cardiovascular events were available for all
      randomized patients. INTERVENTIONS: The nonpharmacological special intervention
      programme was based on one information meeting followed by five weekly 2-h
      sessions with participation of patients and spouses. The diet recommendations
      were similar to established guidelines. Overweight patients were instructed to
      lose weight, and diabetic patients were systematically taught self-monitoring of
      blood glucose. Smokers were invited to a smoking cessation programme with five
      weekly meetings. Follow-up visits were thereafter scheduled every 6 months. Lipid
      lowering drugs were recommended in the intervention group if the treatment goals
      using nonpharmacological measures were not achieved. Patients in the usual care
      group were told to quit smoking and to lower their consumption of fat and
      glucose. Antihypertensive treatment (i.e., selection of drugs) was on purpose
      kept similar in the two groups. MAIN OUTCOME MEASURES: The IMT of the common
      carotid artery as measured by ultrasound. Cardiovascular events during follow-up.
      RESULTS: Significant net reductions were seen for serum cholesterol,
      triglycerides, fasting glucose and smoking. No difference in change in IMT was
      observed during follow-up between the two randomization groups. The explanation
      was that patients with positive plaque status at baseline had a much larger
      increase in IMT over time than patients with negative plaque status, and that
      patients with positive plaque status more often survived and were available for
      re-examination after 6 years in the intervention group than in the usual care
      group. Total mortality was lower in the intervention group, compared with the
      usual care group, 13 and 29%, respectively (P=0.028). CONCLUSIONS: In high risk
      populations, long-term studies with surrogate endpoints may be misleading because
      of missing data in patients where a large increase in IMT would have been
      observed, had they been re-examined. Another important conclusion from our study
      was that the gloomy prognosis for this patient category may be improved by a
      dedicated risk factor intervention programme. The improved prognosis was observed
      mainly in those patients at highest risk judged from history of cardiovascular
      disease or positive ultrasound plaque status at baseline.

PMID- 11298851
TI  - Marital status and cardiovascular risk in French and Swedish automotive industry
      workers--cross sectional results from the Renault-Volvo Coeur study.
AB  - OBJECTIVES: To compare the coronary risk profiles in a sample of the French and
      Swedish automotive industry employees who were married/cohabitant, divorced or
      single (never married). DESIGN: A cross-sectional study comparison from
      biological and questionnaire data between the French and Swedish samples.
      SETTING: Occupational health departments at Renault (employees from the north
      west of France) and Volvo (employees from the south-west of Sweden). SUBJECTS:
      Two random samples of males aged between 45 and 50 years were examined in 1993,
      from Renault 1000, and from Volvo 1000. MAIN OUTCOME MEASURES: Biological data
      including cholesterol, blood pressure as well as the Framingham risk index. Self
      reported information regarding marital status, smoking, exercise, alcohol habits,
      and work stress assessed by the Karasek method, private social support indices,
      and type A behaviour according to the Bortner scale. RESULTS: More employees were
      married/cohabitant and fewer divorced or single at Renault. Apart from waist/hip
      ratio being marginally lower in Swedish single men, compared with married and
      divorced, no significant difference in biological cardiac risk factors (total
      cholesterol, blood pressure or Framingham risk index) was seen between the
      subgroups from any of the two countries. Compared with married/cohabitant men, it
      was shown that in men living alone smoking was more prevalent at Renault and
      Volvo. These men also showed less type A behaviour, a lower work control and a
      lower work support and fewer close friends. Alcohol consumption was reported in
      smaller amounts for Volvo employees living alone compared with married or
      divorced employees. Married/cohabitant and divorced staff showed similar values
      regarding all measured variables when compared within each country. CONCLUSIONS:
      Employees living alone in both France (Renault) and Sweden (Volvo) automotive
      companies seem to have increased nontraditional cardiac risk factors pertaining
      to life style and social network compared with married or divorced men. These
      results, in combination with the finding that more Volvo than Renault employees
      were living alone, suggest a higher risk for coronary heart disease amongst Volvo
      employees. This hypothesis will be evaluated in the 5 and 10 years follow up
      study.

PMID- 11298852
TI  - Introduction.

PMID- 11298853
TI  - The use of nonhuman primate models to improve gene transfer into haematopoietic
      stem cells.
AB  - Primitive haematopoietic progenitor and stem cells (HSC) have been pursued as
      highly desirable targets for genetic therapy as technology allowing safe and
      controllable transfer of exogenous genes into eukaryotic cells was developed a
      decade ago. Retroviral vectors have been used for the majority of preclinical and
      clinical studies directed at these cells, because these vectors have a number of
      the necessary properties, including chromosomal integration, helper-free
      production systems, and lack of toxicity. Until recently, however, results with
      these vectors in clinical trials and large animal models indicated efficiency of
      gene transfer as a major hurdle to be overcome. We have focused on using the
      rhesus macaque autologous transplantation model to optimize gene transfer to
      primitive haematopoietic cells, and investigate questions regarding in vivo stem
      cell behaviour, in a system with proven predictive value for human
      haematopoiesis. By optimization of transduction conditions using standard
      vectors, gene transfer efficiency to primitive repopulating cells has reached the
      clinically relevant range of 5-20% long-term. Alternative vector systems, have
      also yielded promising results. We have also found that relatively simple
      manipulation of cell cycle status prior to reinfusion of marked cells results in
      significantly improved engraftment of transduced cells: this finding may have an
      impact particularly in the nonablative setting. The high level marking has
      permitted insertion site analysis and clonal tracking in vivo. Inverse PCR and/or
      a ligation-mediated PCR procedure have demonstrated that a large number of
      transduced clones (over 50) contribute to multiple lineages in vivo for up to at
      least 2 years post-transplantation. Thus far we have little evidence for rapid
      clonal succession or lineage-restricted engraftment of transduced cells. These
      and other advances should result in successful gene therapy for a variety of
      acquired and congenital disorders affecting HSCs and their progeny lineages.

PMID- 11298854
TI  - Lentiviral-mediated gene transfer into haematopoietic stem cells.
AB  - OBJECTIVES: Lentiviral vectors can transduce nondividing cells. As most
      haematopoietic stem cells (HSCs) are nondividing in vivo, lentiviral vectors are
      promising viral vectors to transfer genes into HSCs. DESIGN AND SETTING: We have
      used HIV-1 based lentiviral vectors containing the green fluorescent protein
      (GFP) gene to transduce umbilical cord blood CD34+ and CD34+/CD38- cells prior to
      transplantation into NOD/SCID mice. RESULTS: High level engraftment of human
      cells was obtained and transgene expression was seen in both myeloid and lymphoid
      lineages. Bone marrow from the primary transplant recipients mice was
      transplanted into secondary recipients. GFP expression was seen in both lymphoid
      and myeloid cells in the secondary recipients 6 weeks posttransplantation. Human
      haematopoietic progenitor colonies were grown from both primary and secondary
      recipients. Over 50% of the haematopoietic colonies in these recipients were
      positive for the GFP transgene by PCR. Following inverse PCR, amplified fragments
      were sequenced and integration of the vector into human genomic DNA was
      demonstrated. Several vectors containing different internal promoters were tested
      in NOD/SCID mice that had been transplanted with transduced CD34+ and CD34+/CD38-
      cells. The elongation factor-1alpha (EF-1alpha) promoter gave the highest level
      of expression, both in the myeloid and lymphoid progeny of the engrafting cells.
      CONCLUSIONS: These data collectively indicate that candidate human HSCs can be
      efficiently transduced with lentiviral vectors and that the transgene is highly
      expressed in their progeny cells.

PMID- 11298855
TI  - Gene transfer and the treatment of haematological malignancy.
AB  - Gene therapy offers an additional therapeutic modality for treating
      haematological malignancy. Because gene therapies could be truly specific for the
      malignancy, they should ultimately prove both safe and effective. We have far to
      go before this full potential is realized, but gene transfer strategies are
      already showing therapeutic promise. Gene transfer may be used to correct the
      genetic defect in the tumour, to render it more susceptible to conventional
      therapies, or the normal host cells more resistant, to induce or amplify an
      antitumour immune response, or simply as a means of tracking the tumour or cells
      used for treatment. This article describes examples of each approach and
      discusses future prospects for the field.

PMID- 11298856
TI  - Suicide gene therapy: possible applications in haematopoietic disorders.
AB  - Although the treatment results for some forms of haematologic malignancies are
      excellent, especially for the childhood acute leukaemias, there is still a
      significant fraction of patients that will not benefit from the therapy available
      today. The identification of new techniques, such as gene therapy, may therefore
      be of great importance for future therapeutic applications. Suicide gene therapy
      is one of several gene therapeutic approaches to treat cancer. A suicide gene is
      a gene encoding a protein, frequently an enzyme, that in itself is nontoxic to
      the genetically modified cell. However, when a cell is exposed to a specific
      nontoxic prodrug, this is selectively converted by the gene product into toxic
      metabolites that kill the cell. The suicide gene most commonly employed, both in
      experimental and a clinical settings, is herpes simplex thymidine kinase (HSVtk).
      Some suicide gene products also induce a so-called 'bystander effect', i.e. a
      toxic effect on adjacent nongene modified tumour cells and sometimes also on more
      distant tumour cells. The bystander effect is most evident in tumour cells that
      have a high number of gap junctions, cellular channels build up by proteins
      called connexins. Many tumours, amongst them many haematological ones, have a low
      number of gap junctions. Therefore, it is important to develop gap junction
      independent drug delivery systems. Suicide gene technology may also be used for
      the ex vivo purging of tumour cells in bone marrow or peripheral blood stem cell
      autografts or for inactivation of effector cells, such as antitumour T donor
      lymphocytes in allogeneic transplantation to prevent severe graft versus host
      reactions. New constructs, e.g. combining suicide genes and immune response
      enhancing genes or suicide genes and connexin inducing genes may further improve
      the value of suicide gene therapy.

PMID- 11298857
TI  - Use of suicide gene-expressing donor T-cells to control alloreactivity after
      haematopoietic stem cell transplantation.
AB  - Conditional ablation of alloreactive donor T-cells to prevent or treat graft
      versus-host disease (GvHD) in the context of allogeneic haematopoietic stem cell
      transplantation could significantly contribute to expand the use of
      alloreactivity as a treatment modality. The prevention and treatment of GvHD
      induced by herpes simplex virus 1-thymidine kinase (HS-tk)-expressing donor T
      cells by ganciclovir (GCV) has been demonstrated. Early clinical findings suggest
      that the use of such cells early or late after transplantation is associated with
      no acute toxicity, persistent circulation of the gene-modified cells (GMC) and
      GCV-sensitive GvHD. However, a number of limitations such as reduced immune
      function of gene-modified T-cells, immunogenicity of GMC as well as presence of a
      truncated HS-tk gene have emerged and need to be addressed.

PMID- 11298858
TI  - Gene therapy for genetic haematological disorders and immunodeficiencies.
AB  - Gene transfer and autologous transplantation of haematopoietic stem cells (HSCs)
      from patients with genetic haematological disorders and immunodeficiencies could
      provide the same benefits as allogeneic HSC transplantation, without the
      attendant immunological complications. Inefficient gene delivery to human HSCs
      has imposed the major limitation to successful application of gene therapy. A
      recently reported clinical trial of gene transfer into HSCs of infants with X
      linked severe combined immunodeficiency (SCID) has achieved immune restoration
      because of the selective outgrowth of the gene-corrected lymphocytes. Newer
      methods for manipulating HSCs may lead to efficacy for other disorders. The
      problems and progress in this area are reviewed herein.

PMID- 11298860
TI  - Diamond colour centres as a nanoscopic light source for scanning near-field
      optical microscopy.
AB  - Recently it was shown that a single molecule at cryogenic temperatures could be
      used as a local light source for illumination of a sample in the near field.
      Conventional light-emitting systems such as dye molecules and semiconductor
      quantum dots could also be used for this purpose, but they suffer from lack of
      photostability. However, colour centres in diamond have been found to be
      remarkably stable against bleaching and blinking effects. Here we present the
      first SNOM images taken with nanoscopic diamond crystals as a light source.

PMID- 11298861
TI  - Near-field optical microscopy based on microfabricated probes.
AB  - We demonstrate high resolution imaging with microfabricated, cantilevered probes,
      consisting of solid quartz tips on silicon levers. The tips are covered by a 60
      nm thick layer of aluminium, which appears to be closed at the apex when
      investigated by transmission electron microscopy. An instrument specifically
      built for cantilever probes was used to record images of latex bead projection
      patterns in transmission as well as single molecule fluorescence. All images were
      recorded in constant height mode and show optical resolutions down to 32 nm.

PMID- 11298862
TI  - Microfabricated silicon dioxide cantilever with subwavelength aperture.
AB  - We have developed a microfabricated SiO2 cantilever with subwavelength aperture
      for scanning near-field optical microscopy (SNOM), to overcome the disadvantages
      of conventional optical fibre probes such as low reproducibility and low optical
      throughput. The microcantilever, which has a SiO2 cantilever and an aperture tip
      near the end of the cantilever, is fabricated in a reproducible batch process.
      The circular aperture with a diameter of 100-150 nm is formed by a focused ion
      beam technique. Incident light is directly focused on the aperture from the rear
      side of the cantilever using a focusing objective, and high optical throughput
      (10(-2) to 10(-3)) is obtained. The microcantilever can be operated as a SNOM
      probe in contact mode or in dynamic mode.

PMID- 11298863
TI  - Moulded photoplastic probes for near-field optical applications.
AB  - The inexpensive fabrication of high-quality probes for near-field optical
      applications is still unsolved although several methods for integrated
      fabrication have been proposed in the past. A further drawback is the intensity
      loss of the transmitted light in the 'cut-off' region near the aperture in
      tapered optical fibres typically used as near-field probes. As a remedy for these
      limitations we suggest here a new wafer-scale semibatch microfabrication process
      for transparent photoplastic probes. The process starts with the fabrication of a
      pyramidal mould in silicon by using the anisotropic etchant potassium hydroxide.
      This results in an inverted pyramid limited by < 111 > silicon crystal planes
      having an angle of approximately 54 degrees. The surface including the mould is
      covered by a approximately 1.5 nm thick organic monolayer of
      dodecyltrichlorosilane (DTS) and a 100-nm thick evaporated aluminium film. Two
      layers of photoplastic material are then spin-coated (thereby conformal filling
      the mould) and structured by lithography to form a cup for the optical fibre
      microassembly. The photoplastic probes are finally lifted off mechanically from
      the mould with the aluminium coating. Focused ion beam milling has been used to
      subsequently form apertures with diameters in the order of 80 nm. The advantage
      of our method is that the light to the aperture area can be directly coupled into
      the probe by using existing fibre-based NSOM set-ups, without the need for far
      field alignment, which is typically necessary for cantilevered probes. We have
      evidence that the aluminium layer is considerably smoother compared to the
      'grainy' layers typically evaporated on free-standing probes. The optical
      throughput efficiency was measured to be about 10-4. This new NSOM probe was
      directly bonded to a tuning fork sensor for the shear force control and the
      topography of a polymer sample was successfully obtained.

PMID- 11298864
TI  - High-resolution constant-height imaging with apertured silicon cantilever probes.
AB  - We present high-resolution aperture probes based on non-contact silicon atomic
      force microscopy (AFM) cantilevers for simultaneous AFM and near-infrared
      scanning near-field optical microscopy (SNOM). For use in near-field optical
      microscopy, conventional AFM cantilevers are modified by covering their tip side
      with an opaque aluminium layer. To fabricate an aperture, this metal layer is
      opened at the end of the polyhedral probe using focused ion beams (FIB). Here we
      show that apertures of less than 50 nm can be obtained using this technique,
      which actually yield a resolution of about 50 nm, corresponding to lambda/20 at
      the wavelength used. To exclude artefacts induced by distance control, we work in
      constant-height mode. Our attention is particularly focused on the distance
      dependence of resolution and to the influence of slight cantilever bending on the
      optical images when scanning at such low scan heights, where first small
      attractive forces exerted on the cantilever become detectable.

PMID- 11298865
TI  - Spatial distribution and polarization dependence of the optical near-field in a
      silicon microfabricated probe.
AB  - This paper reports on the spatial distribution and polarization behaviour of the
      optical near-field at the aperture of a Si micromachined probe. A sub-100 nm
      aperture at the apex of a SiO2 tip on a Si cantilever was successfully fabricated
      by selective etching of the SiO2 tip in a buffered-HF solution using a thin Cr
      film as a mask. The aperture, 10-100 nm in size, can be reproducibly fabricated
      by optimizing the etching time. The optical throughput of several apertures was
      measured. For a 100 nm aperture, a throughput of 1% was approved. The probe shows
      a very high optical throughput owing to the geometrical structure of the tip. The
      spatial distribution of the near-field light is measured and simulated using a
      finite difference-time domain method. The polarization behaviour of apertures
      with different shapes was analysed using a photon counting camera system.

PMID- 11298866
TI  - Silicon technology-based micro-systems for atomic force microscopy/photon
      scanning tunnelling microscopy.
AB  - We developed silicon nitride cantilevers integrating a probe tip and a wave guide
      that is prolonged on the silicon holder with one or two guides. A micro-system is
      bonded to a photodetector. The resulting hybrid system enables us to obtain
      simultaneously topographic and optical near-field images. Examples of images
      obtained on a longitudinal cross-section of an optical fibre are shown.

PMID- 11298867
TI  - Transmission line probe based on a bow-tie antenna.
AB  - A high transmission probe for scanning near-field optical microscopy is discussed
      that is based on a bow-tie antenna. The proposed design of the transmission line
      probe relies on batch-fabricated hollow pyramidal silicon dioxide tips that are
      partly coated with aluminium to accomplish the tapered dipole antenna.
      Theoretical calculations of the field distribution were performed to investigate
      its optical properties. Results were compared with those of conventional aperture
      tips based on the same silicon dioxide tip configuration, and revealed unique
      properties with respect to the transmission efficiency.

PMID- 11298868
TI  - Shaping the reflection near-field optical probe: finite domain time difference
      modelling and fabrication using a focused ion beam.
AB  - An optical fibre ending in a trihedral tip is proposed as a convenient probe for
      reflection near-field optical microscopy in emission/collection mode. Its shape
      is obtained by ion milling. A first example of manufacturing and numerical models
      using the bi-dimensional FDTD method is presented. It confirms the strong
      influence of the facet angle on the intensity reflected by the probe, which is
      predicted by a rough analysis. This method can help us to optimize the
      'reflection probe' by reducing this offset signal.

PMID- 11298869
TI  - Design and optimization of tapered structure of near-field fibre probe based on
      finite-difference time-domain simulation.
AB  - The finite-difference time-domain method was employed to simulate light
      propagation in tapered near-field fibre probes with small metal aperture. By
      conducting large-volume simulations, including tapered metal-cladding waveguide
      and connected optical fibre waveguide, we illustrated the coupling between these
      guiding modes as well as the electric field distribution in the vicinity of the
      aperture. The high collection efficiency of a double-tapered probe was reproduced
      and was ascribed to the shortening of the cut-off region and the efficient
      coupling to the guiding mode of the optical fibre. The dependence of the
      efficiency on the tapered structure parameters was also examined.

PMID- 11298870
TI  - SNOM/STM using a tetrahedral tip and a sensitive current-to-voltage converter.
AB  - Scanning near-field optical microscopes (SNOM) using the tetrahedral-tip (T-tip)
      with scanning tunnelling microscopy (STM) distance control have been realized in
      transmission and reflection mode. Both set-ups used ordinary STM current-to
      voltage converters allowing measurement of metallic samples. In the transmission
      mode, a resolution of 10 nm to 1 nm with regard to material contrast can be
      achieved on binary metal samples. Because of the great near-field optical
      potential of the T-tip with respect to the optical resolution, it is a
      challenging task to find out whether these results can be transferred to non
      metallic sample systems as well. This paper reports on a newly designed SNOM/STM
      transmission mode set-up using the tetrahedral-tip. It implements a sensitive
      current-to-voltage converter to widen the field of measurable sample systems.
      Beyond this, mechanical and optical measuring conditions are substantially
      improved compared to previous set-ups. The new set-up provides a basis for the
      routine investigation of metal nanostructures and adsorbed organic monolayers at
      resolutions in the 10 nm range.

PMID- 11298871
TI  - Non-regularly shaped plasmon resonant nanoparticle as localized light source for
      near-field microscopy.
AB  - We study numerically two-dimensional nanoparticles with a non-regular shape and
      demonstrate that these particles can support many more plasmon resonances than a
      particle with a regular shape (e.g. an ellipse). The electric field distributions
      associated with these different resonances are investigated in detail in the
      context of near-field microscopy. Depending on the particle shape, extremely
      strong and localized near-fields, with intensity larger than 105 that of the
      illumination wave, can be generated. We also discuss the spectral dependence of
      these near-fields and show that different spatial distributions are observed,
      depending which plasmon resonance is excited in the particle.

PMID- 11298872
TI  - The role of tip plasmons in near-field Raman microscopy.
AB  - The enhancement in electric field strength in the vicinity of a metal tip,
      through the excitation of plasma modes in the tip, is investigated using the
      finite difference time domain method; such tip enhancement has significant
      potential for application in scanning near-field Raman microscopy. To represent
      an experimentally realistic geometry the near-field probe is described by a
      conical metal tip with a spherical apex, with radii 20 nm and 200 nm considered,
      in close proximity to a glass substrate. Illumination through the substrate is
      considered, both at normal incidence and close to the critical angle, with the
      polarization in the plane of incidence. By modelling the frequency dependent
      dielectric response of the metal tip we are able to highlight the dependence on
      the scattering geometry of the nature of the electromagnetic excitations in the
      tip. In particular, the strongest electric field enhancement with the greatest
      confinement occurs for the excitation of modes localized at the tip apex, excited
      only for off-normal incidence. Bulk modes excited in the tip also produce
      enhancement, although over a larger area and with significantly less enhancement
      than that of the localized modes; however, the excitation of bulk modes is
      independent of the angle of incidence.

PMID- 11298873
TI  - A single gold particle as a probe for apertureless scanning near-field optical
      microscopy.
AB  - We report on the fabrication, characterization and application of a probe
      consisting of a single gold nanoparticle for apertureless scanning near-field
      optical microscopy. Particles with diameters of 100 nm have been successfully and
      reproducibly mounted at the end of sharp glass fibre tips. We present the first
      optical images taken with such a probe. We have also recorded plasmon resonances
      of gold particles and discuss schemes for exploiting the wavelength dependence of
      their scattering cross-section for a novel form of apertureless scanning near
      field optical microscopy.

PMID- 11298874
TI  - Pure optical contrast in scattering-type scanning near-field microscopy.
AB  - We have enhanced the apertureless scattering-type scanning near-field optical
      microscope by two improvements which together achieve a recording of the true
      near field without any height-induced artefact. These are the use of
      interferometric detection of the scattered light on one hand, and the use of
      higher-harmonic dither demodulation of the scattered signal on the other. Here we
      present the basic rationale for these techniques, and give examples measured with
      two different experiments, one in the infrared (10 microm wavelength), the other
      in the visible (633 nm). The latter operates in a fully heterodyne mode and
      displays simultaneous images of optical near-field phase and amplitude, at below
      10 nm resolution.

PMID- 11298875
TI  - Optical near-field harmonic demodulation in apertureless microscopy.
AB  - Spatial derivatives of the optical fields scattered by a surface can be
      investigated by apertureless near-field optical microscopy by modulating
      sinusoidally the probe to sample distance and detecting the optical signal at the
      first and higher harmonics. Demodulation up to the fifth harmonic order has been
      accomplished on a sample of close-packed latex spheres by means of the silicon
      tip of a scanning interference apertureless microscope. The working principles of
      such microscope are reviewed. The experimental configuration used comprises a
      tuning-fork-based tapping-mode atomic force microscope for the distance
      stabilization, and a double-modulation technique for complete separation of the
      topography tracking from the optical detection. Simple modelling provides first
      indications for the interpretation of experimental data. The technique described
      here provides either artefact-free near-field optical imaging, or detailed
      information on the structure of the near fields scattered by a surface.

PMID- 11298876
TI  - Apertureless near-field optical microscopy via local second-harmonic generation.
AB  - We describe an apertureless scanning near-field optical microscope (SNOM) based
      on the local second-harmonic generation enhancement resulting from an
      electromagnetic interaction between a probe tip and a surface. The imaging
      mechanisms of such apertureless second-harmonic SNOM are numerically studied. The
      technique allows one to achieve strongly confined sources of second-harmonic
      light at the probe tip apex and/or surface area under the tip. First experimental
      realization of this technique has been carried out using a silver-coated fibre
      tip as a probe. The experiments reveal a strong influence of the tip-surface
      interaction as well as polarization of the excitation light on images obtained
      with apertureless second-harmonic SNOM. The technique can be useful for studying
      the localized electromagnetic excitations on surfaces as well as for
      visualization of lateral variations of linear and nonlinear optical properties of
      surfaces.

PMID- 11298877
TI  - Photocatalytic deposition of a gold nanoparticle onto the top of a SiN cantilever
      tip.
AB  - We propose a new technique for depositing a gold nanoparticle onto the tip of a
      dielectric support. We employed the photocatalytic effect of titanium dioxide for
      the deposition. When the titanium dioxide immersed in a solution including gold
      ions is subject to optical exposure, the excited electrons in the conduction band
      reduce gold ions into gold metal. Illumination by an evanescent wave generated
      with a total reflection configuration limits the deposition region to the very
      tip. In experiments we obtained 100-300 nm gold particles on SiN cantilever tips
      for atomic force microscopes. The contrast of evanescent interference fringes
      measured by a near-field scanning optical microscope with this gold nanoparticle
      probe has proved to be higher than that with a non-deposited SiN probe by a
      factor of 1.5.

PMID- 11298879
TI  - Near-field optical probing of two-dimensional photonic crystals: theory and
      experiment.
AB  - We report new experimental results, and their theoretical analysis, on the
      mechanisms that control light transfer between two integrated waveguides
      connected by two-dimensional matrices of dielectric pillars. The optical
      properties of the system are analysed from the well-established formalism of
      classical field susceptibilities (Green dyadic functions). We apply this scheme
      to investigate the optical properties of two-dimensional arrays connected to two
      integrated waveguides. Comparisons with current experimental work based on near
      field optical probing are provided together with a spectral analysis of the
      phenomenon.

PMID- 11298878
TI  - Local phase measurements of light in a one-dimensional photonic crystal.
AB  - For the first time the local optical phase evolution in and around a small, one
      dimensional photonic crystal has been visualized with a heterodyne
      interferometric photon scanning tunnelling microscope. The measurements show an
      exponential decay of the optical intensity inside the crystal, which consists of
      a periodic array of subwavelength air rods fabricated in a conventional ridge
      waveguide. In addition it is found that the introduction of the air rods has a
      counterintuitive effect on the phase development inside the structure. The
      heterodyne detection scheme allows the detection of low-intensity scattered
      waves. In the vicinity of the scattering air rods phase singularities are found
      with a topological charge of plus or minus one.

PMID- 11298880
TI  - Mapping and manipulating whispering gallery modes of a microsphere resonator with
      a near-field probe.
AB  - We report high spatial resolution mapping of high-Q whispering gallery modes in
      microsphere resonators with a near-field probe. We present experimental results
      on the effect of Q-factor degradation when the probe interacts with the
      evanescent field and discuss future applications of our experimental set-up for
      realization of novel nanolasers and nano light-emitting-diodes.

PMID- 11298881
TI  - Light field propagation by metal micro- and nanostructures.
AB  - The ability to sustain plasmon oscillations gives rise to unique properties of
      metal nanostructures, which can be exploited for the controlled manipulation of
      light fields on the nanoscale. In this context we investigate electromagnetic
      coupling effects within lithographically produced ensembles of gold nanoparticles
      with a photon scanning tunnelling microscope. To provide an interface between
      these nano-optical devices and classical far-field optics, we investigate surface
      plasmon propagation on microstructured metal thin films.

PMID- 11298882
TI  - Local field enhancement effects for nanostructuring of surfaces.
AB  - We report on a method that allows the nanostructuring of surfaces with intense
      laser pulses. For this purpose isolated polystyrene spheres with diameters in the
      order of the laser wavelength were deposited on a silicon or glass surface.
      Illumination with short and ultrashort laser pulses produced holes underneath
      these particles. Calculations of the field near the particles make clear that
      geometrical optics, that is, focusing by a spherical lens, as well as near-field
      effects, contribute to the size and shape of these holes. This technique can be
      utilized for the parallel structuring of large surface areas with a single laser
      shot.

PMID- 11298883
TI  - Experimental statistics of near-field intensity distributions at nanostructured
      surfaces.
AB  - Scanning near-field optical microscopy is a technique in which the resolution is
      primarily determined by the size of a probe and not by the wavelength of
      illumination as in classical (far-field) microscopy. However, the relationship
      between a sample and its near-field optical image is usually rather complex.
      Typical factors responsible, at least partially, for such a complexity are the
      conditions of illumination and detection, sample characteristics (e.g. roughness
      and dielectric constant) and optical properties of the probe. Theoretical and
      experimental works conducted to improve our understanding of the relation between
      the object and the image have been reported (Greffet & Carminati, 1997).
      Recently, with the help of a photon scanning tunnelling microscope we have
      carried out an extensive study of the resultant near-field intensity
      distributions due to the elastic (in the plane) scattering of surface plasmon
      polaritons (SPPs) at metal film surfaces. We have also directly observed (in
      similar experimental conditions) localized dipolar excitations in silver colloid
      fractals (Bozhevolnyi et al., 1998). In both cases, the studied phenomena are
      intimately related to the regime of multiple light scattering, in which the
      interference effects are rather complicated and therefore a proper interpretation
      of them was far from being trivial. Thus, even though a certain understanding of
      many features inherent to the subwavelength light interference phenomena was
      gained (Bozhevolnyi & Coello, 1998; Bozhevolnyi et al., 1998; Coello &
      Bozhevolnyi, 1999), it is clear from the outcome of the investigations that more
      systematic studies in this context are still needed. A different and more
      powerful approach may be a statistical study of the recorded near-field intensity
      distributions. In this work, we report what we believe to be the first results on
      experimental statistics of near-field optical images exhibiting localized optical
      excitations (related to the regime of multiple scattering of light). We
      investigated optical images obtained with SPPs excited at different light
      wavelengths and scattered at different film surfaces, and with different
      polarizations and wavelengths of light scattered by silver colloid fractal
      structures. We have found significant differences in statistics between near
      field intensity distributions taken at rough and smooth metal film surfaces and
      fractal structures. Finally, our predictions seem to be in agreement with
      theoretical studies reported by other authors (Sanchez-Gil & Garcia-Ramos, 1998).

PMID- 11298884
TI  - Fundamental differences between micro- and nano-Raman spectroscopy.
AB  - Electric field polarization orientations and gradients close to near-field
      scanning optical microscope (NSOM) probes render nano-Raman fundamentally
      different from micro-Raman spectroscopy. With x-polarized light incident through
      an NSOM aperture, transmitted light has x, y and z components allowing nano-Raman
      investigators to probe a variety of polarization configurations. In addition, the
      strong field gradients in the near-field of a NSOM probe lead to a breakdown of
      the assumption of micro-Raman spectroscopy that the field is constant over
      molecular dimensions. Thus, for nano-Raman spectroscopy with an NSOM, selection
      rules allow for the detection of active modes with intensity dependent on the
      field gradient. These modes can have similar activity as infra-red absorption
      modes. The mechanism can also explain the origin and intensity of some Raman
      modes observed in surface enhanced Raman spectroscopy.

PMID- 11298885
TI  - The correlation between polarization modulated near-field optical images and the
      anisotropy of the probe.
AB  - The true anisotropic images taken with the polarization modulation near-field
      optical microscope are often influenced by the linear dichroism of the tapered
      fibre probe. In this paper, we develop a new method to separate the anisotropic
      image form probe's dichroism. Our calculations show that the near-field optical
      image is simply a vector sum of the sample's dichroism and the probe's dichroism,
      when the probe's anisotropy is small. With this result, we demonstrate the true
      anisotropic images of poly(phenylene vinylene) (PPV) thin films. The PPV films
      show non-uniform mesoscale dichroic domains with average domain size,
      approximately 0.3 mm, and the coefficient for linear dichroism is 1.25 x 10(4)
      cm(-1).

PMID- 11298886
TI  - Non-optical tip-sample distance control method for scanning near-field optical
      microscopy using a piezoresistive micro cantilever.
AB  - A piezoresistive micro cantilever is applied to monitor the displacement of an
      optical fibre probe and to control tip-sample distance. The piezoresistive
      cantilever was originally made for a self-sensitive atomic force microscopy (AFM)
      probe and has dimensions of 400 microm length, 50 microm width and 5 microm
      thickness with a resistive strain sensor at the bottom of the cantilever. We
      attach the piezoresistive cantilever tip to the upper side of a vibrating bent
      optical fibre probe and monitor the resistance change amplitude of the strain
      sensor caused by the optical fibre displacement. By using this resistance change
      to control the tip-sample distance, the two-cantilever system successfully
      provides topographic and near-field optical images of standard samples in a
      scanning near-field optical microscopy (SNOM)/AFM system. A resonant
      characteristic of the two-cantilever system is also simulated using a mechanical
      model, and the results of simulation correspond to the experimental results of
      resonance characteristics.

PMID- 11298887
TI  - Non-optically probing near-field microscopy with illumination of total internal
      reflection.
AB  - We have developed a non-optically probing near-field microscope with illumination
      of total internal reflection. Because the illumination light does not pass
      through the specimens, it is possible to observe thick specimens or highly
      absorptive materials. It reduces the background noise because the decay length of
      the evanescent wave is a few hundred nanometres. We found that although in the
      total internal reflection illumination system the light passed through the
      photosensitive film and illuminated the specimen, it did not affect the
      photosensitive film severely and did not limit the resolution. The imaging
      properties of reflection illumination and transmission illumination are analysed
      using a finite-differential time domain method.

PMID- 11298888
TI  - Tapping-mode tuning-fork near-field scanning optical microscopy of low power
      semiconductor lasers.
AB  - The newly developed inverted tapping-mode tuning-fork near-field scanning optical
      microscopy (TMTF-NSOM) is used to study the local near-field optical properties
      of strained AlGaInP/Ga0.4In0.6P low power visible multiquantum-well laser diodes.
      In contrast to shear-force mode NSOM, TMTF-NSOM provides the function to acquire
      the evanescent wave intensity ratio /I(2omega)/ / /I(omega)/ image, from which
      the evanescent wave decay coefficient q can be evaluated for a known tapping
      amplitude. Moreover, we probe the near-field stimulated emission spectrum, which
      gives the free-space laser light wavelength lambda(o) and the index of refraction
      nr of the laser diode resonant cavity. Once q, lambda(o), and n(r) are all
      measured, we can determine the angle of incidence theta(o) of the dominant
      totally internally reflected waves incident on the front mirror facet of the
      resonator. Determination of such an angle is very important in modelling the
      stability of the laser diode resonator.

PMID- 11298889
TI  - Separating different contributions to the shear force in near-field microscopy.
AB  - The shear force between a gold and a graphite sample and an approaching near
      field optical probe using tuning fork detection is studied in detail. The
      adiabatic and dissipative contributions are clearly distinguished by monitoring
      the amplitude as well as the phase of the tip vibration when approaching the
      surfaces. Their relative strengths vary differently but characteristically with
      the distance. The interaction starts in case of graphite at a much larger
      distance. The adiabatic contribution is larger in the case of gold, whereas
      graphite shows mostly dissipative interaction. Measurements at various
      temperatures are performed using a gold sample, showing a dependence of the shear
      force on the temperature.

PMID- 11298890
TI  - Well-shaped fibre tips by pulling with a foil heater.
AB  - The length of the molten zone determines the length of pulled optical fibre tips.
      Tips produced by laser or filament heating are rather lengthy. By using a foil
      heater the taper length can be shortened and cone angles in the order of 30
      degrees can reproducibly be obtained. For varying the drawing force there is an
      optimum temperature range where the taper shape is monotonic for the whole tip.
      The tip end diameter is well below 100 nm for optimized pulling conditions.

PMID- 11298891
TI  - Photoconductive imaging in a photon scanning tunnelling microscope capable of
      point-contact current sensing using a conductive fibre probe.
AB  - A photoconductive photon scanning tunnelling microscope was developed to
      investigate the point-contact photoconductive properties of condensed matter. In
      order to detect the current and the optical signal at a local point on a surface,
      we coated the edge of a bent type fibre probe with indium tin oxide. Thus it was
      possible to measure both photocurrent and optical property with subwavelength
      resolution. The performance of the novel microscope was evaluated by analysing an
      organic thin film of copper phthalocyanine (CuPc), which is known to be an
      efficient photoconductive material. Photocurrent and current-voltage
      characteristics were observed at the local point on the CuPc thin films.
      Furthermore, photoconductive images were obtained with topography and near-field
      optical imaging using this system. The photoconductive PSTM shows potential in
      various areas of future optics and electronics.

PMID- 11298892
TI  - Low temperature near-field luminescence studies of localized and delocalized
      excitons in quantum wires.
AB  - Excitons in a GaAs quantum wire were studied in high-resolution photoluminescence
      experiments performed at a temperature of about 10 K with a spatial resolution of
      160 nm and a spectral resolution of 100 microeV. We report the observation of
      quasi-one-dimensional excitons which are delocalized over a length of up to
      several micrometres along the quantum wire. Such excitons give rise to a 10 meV
      broad luminescence band, representing a superposition of transitions between
      different delocalized states. In addition, we find a set of sharp luminescence
      peaks from excitons localized on a sub150 nm length scale. Theoretical
      calculations of exciton states in a disordered quasi-one-dimensional potential
      reproduce the experimental results.

PMID- 11298893
TI  - Low-temperature near-field spectroscopy of CdTe quantum dots.
AB  - A near-field optical microscope has been developed for operation at low
      temperature. This microscope is used to study the photoluminescence of CdTe-based
      quantum dots. Spectra collected upon approaching the optical tip into the near
      field region of the sample reveal the evolution from a broad far-field
      luminescence band - that is typical for a large ensemble of dots - to a near
      field structure made up of a few sharp peaks originating from individual dots.
      Experiments carried out in the excitation-collection mode through the optical tip
      allow study of the effect of an increase in excitation power on the near-field
      spectra. It is found that upon increasing the excitation by two orders of
      magnitude, a spatially resolved spectrum progressively transforms back into a
      broad 'far-field-like' spectrum. Photoluminescence images taken by scanning the
      sample under the tip are used to discriminate various contributions coming from
      individual dots.

PMID- 11298894
TI  - Near-field spectroscopy of single quantum dots at room temperature.
AB  - The observation of photoluminescence spectra of self-assembled single InGaAs
      quantum dots at room temperature was performed under weak excitation conditions
      using a near-field scanning optical microscope. Operation in illumination
      collection mode with a highly sensitive double-tapered optical fibre probe
      enabled detection of weak photoluminescence signals at room temperature with high
      efficiency and high spatial resolution. Each single quantum dot was imaged with a
      spatial resolution of about 250 nm, which corresponded to a quarter of the
      wavelength of the photoluminescence from quantum dots. The photoluminescence
      yields of individual quantum dots were widely distributed and were found to
      decrease with photoluminescence energy. This result serves as a clue to be
      pursued for better understanding of the thermal excitation of the carrier from
      confined states in quantum dots.

PMID- 11298895
TI  - Photoluminescence properties of multiple stacked planes of GaN/AlN quantum dots
      studied by near-field optical microscopy.
AB  - We have studied the photoluminescence properties of GaN quantum dots with
      submicrometre lateral resolution by means of near-field scanning optical
      microscopy. The instrument operated at room temperature and was implemented for
      near-ultra-violet spectroscopy in the illumination-mode configuration. The
      analysed sample consisted of several stacked planes of GaN/AlN quantum dots grown
      by molecular beam epitaxy on Si(111) substrate. The photoluminescence maps showed
      islands in the micrometre range emitting at different wavelengths, confirming the
      atomic force microscopy studies on the morphology of similar uncapped samples.

PMID- 11298897
TI  - Near-field optics on silicon-electrolyte junctions.
AB  - A technique allowing near-field photocurrent (PC) mapping of silicon surfaces in
      contact with an electrolyte is presented. The illumination source is an optical
      fibre tip with a 100-nm aperture. A shear force detection system controls the tip
      sample distance while scanning the tip across the silicon-electrolyte interface.
      Topographic and PC images on SiO2/Si mesas both show 300 nm resolution. It is
      shown that this PC contrast is induced by the tip-topography interaction and
      hence the PC resolution is limited by the resolution of the topography. Indeed,
      PC mapping on topography-less patterned porous-silicon/silicon samples shows that
      the lateral resolution is only limited by the aperture size which is of the order
      of 100 nm.

PMID- 11298896
TI  - Autocorrelation spectroscopy on single ultrathin layers of CdSe/ZnSe: hints for a
      non-thermal distribution of excitons in quantum islands.
AB  - Autocorrelation spectroscopy on the basis of thousands of individual near-field
      photoluminescence spectra of single ultrathin CdSe layers at low temperatures
      exhibits a strong positive correlation peak around 18 meV energy with a width of
      5 meV. Using simulations and experiments as a function of temperature and laser
      intensity, we can exclude interpretations along the lines of biexcitons or phonon
      sidebands. We attribute this feature to the splitting of ground state and an
      excited state in individual quantum islands. This interpretation implies that the
      potential minima are rather uniform in size and that the distribution of excitons
      is nonthermal.

PMID- 11298898
TI  - Femtosecond near-field spectroscopy: carrier relaxation and transport in single
      quantum wires.
AB  - Quasi-two-colour femtosecond pump and probe spectroscopy and near-field scanning
      optical microscopy are combined to study the carrier dynamics in single
      semiconductor nanostructures. In temporally, spectrally and spatially resolved
      measurements with a time resolution of 200 fs and a spatial resolution of 200 nm,
      the non-linear change in reflectivity of a single quantum wire is mapped in real
      space and time. The experiments show that carrier relaxation into a single
      quantum wire occurs on a 100 fs time scale at room temperature. Evidence is given
      for a transient unipolar electron transport along the wire axis on a picosecond
      time and 100 nm length scale.

PMID- 11298899
TI  - Femtosecond near-field scanning optical microscopy study of molecular thin films.
AB  - A near-field scanning optical microscope has been combined with a two-colour time
      resolved pump-probe measurement system. It has a noise-equivalent transmittance
      change of 5.0 x 10-5 for a probe pulse with an intensity of 30 nW. The system has
      been used for evaluating molecular thin films that have a domain structure,
      particularly for observing a gate action of the single domains. The results
      include key features to understand an origin of the domains and suggest that the
      film composition is uniform over a distance of several micrometres.

PMID- 11298900
TI  - Near- and far-field second-harmonic imaging of quasi-phase-matching crystals.
AB  - Second-harmonic scanning near- and far-field optical microscopy of an electric
      field poled KTiOPO4 quasi-phase-matching crystal has been accomplished. This has
      been done in order to reveal the walls that form the intersections between
      inverted and non-inverted crystal domains. The domain walls are seen clearly only
      in images recorded by means of second-harmonic generation because of a large
      nonlinear contrast, and they appear as bright stripes when studied in a
      reflection geometry but they are dark when studied in transmission. The images
      show that the duty cycle of the quasi-phase-matching crystal differs from the
      ideal and that the walls are not completely smooth. These effects, in combination
      with the observed scattering from the domain walls, are expected to lower the
      output of the crystal when used for frequency doubling. We conclude that the wall
      thickness is no more than approximately 100 nm, which makes it a suitable test
      object for the resolution capabilities of scanning near-field optical microscopes
      that are used for nonlinear imaging.

PMID- 11298901
TI  - Near-field second harmonic imaging of the c/a/c/a polydomain structure of
      epitaxial PbZrxTi(1-x)O3 thin films.
AB  - Near-field optical second harmonic microscopy has been applied to imaging of the
      c/a/c/a polydomain structure of epitaxial PbZrxTi1-xO3 thin films in the 0 < x <
      0.4 range. Comparison of the near-field optical images and the results of atomic
      force microscopy and X-ray diffraction studies show that an optical resolution of
      the order of 100 nm is achieved. Symmetry properties of the near-field second
      harmonic signal allow us to obtain good optical contrast between the local second
      harmonic generation in c- and a-domains. Experimentally measured near-field
      second harmonic images have been compared with the results of theoretical
      calculations. Good agreement between theory and experiment is demonstrated.

PMID- 11298902
TI  - State-selective optical near-field resonant ionization spectroscopy of atoms near
      a dielectric surface.
AB  - Spin-sensitive optical near-field microscopy and spectroscopy are proposed based
      on the study on the conserved quantities in optical near-field interactions of
      atoms with dielectric surfaces. A two-step photoionization spectra of Cs atoms
      resolving hyperfine structures are demonstrated near a planar dielectric surface
      by using evanescent waves. These techniques of state/spin-selective excitation
      and highly sensitive detection, combined with the techniques of optical pumping,
      will open up possibilities of space- and polarization-sensitive detection of
      optical near-fields using atomic probes. This novel method provides us with a
      useful technique for the observation of polarization nature of the optical near
      field and controlling the spin states of mesoscopic electronic systems.

PMID- 11298903
TI  - Paradigmatic shifts in occlusion and temporomandibular disorders.
AB  - There are several terms that identify proposed paradigms for the way things ought
      to be carried out in the health sciences: evidence-based, cause-and-effect,
      diagnostic gold-standard, patient-centred-outcomes, risk assessment,
      cost/benefit/risk, and efficacious/effective. Collectively these paradigms
      exhibit varying degrees of interdependence, and have the potential for changing
      the way dentistry is practiced. A paradigm can be thought of as a standard by
      which research and health science ought to be conducted and evaluated. In this
      sense scientists and clinicians try to figure out how to account for various
      observations and phenomena dictated by paradigms or models of health care;
      however, it may become necessary to shift to new paradigms that are more
      consistent with scientific and clinically reality. Some of the potential effects
      of these shifting paradigms on the practice and teaching of occlusion and
      temporomandibular disorders are considered.

PMID- 11298904
TI  - Effect of three adhesive primers for a noble metal on the shear bond strengths of
      three resin cements.
AB  - The purpose of this study was to evaluate the durability and shear bond strengths
      of the different combinations of three adhesive primers and three resin cements
      to a silver-palladium-copper-gold (Ag-Pd-Cu-Au) alloy. The adhesive primers Alloy
      Primer (AP), Metal PrimerII (MPII) and Metaltite (MT), and the resin cements
      BistiteII (BRII), Panavia Fluoro Cement (PFC) and Super-Bond C&B (SB) were used.
      Two sizes of casting alloy disks were either non-primed or primed and cemented
      with each of the three resin cements. The specimens were stored in a 37 degrees C
      water bath for 24 h and then immersed alternately in 4 and 60 degrees C water
      baths for 1 min each for up to 100,000 thermal cycles. Shear mode testing at a
      crosshead speed of 0.5 mm/min was then performed. The application of MPII or MT
      was effective for improving the shear bond strength between each of the three
      resin cements and the Ag-Pd-Cu-Au alloy compared with non-primed specimens.
      However, when primed with MPII or MT and cemented with SB, the bond strength at
      100,000 thermal cycles was significantly lower than that at thermal cycle 0. When
      primed with AP, the specimens cemented with BRII or PFC showed lower bond
      strength than non-primed specimens and failed at the metal-resin cement interface
      at 100,000 thermal cycles. On the other hand, AP was effective in enhancing the
      shear bond strength of SB to the Ag-Pd-Cu-Au alloy. The five combined uses of an
      adhesive metal primer and resin cement (combinations of MPII or MT and BRII or
      PFC and AP and SB) are applicable to the cementation of prosthodontic
      restorations without complicated surface modification of the noble alloy.

PMID- 11298905
TI  - Comparison of dentine hypersensitivity in selected occidental and oriental
      populations.
AB  - Epidemiological data on dentine hypersensitivity (DH) prevalence are limited. Few
      studies have compared prevalence between populations. The aim of this
      investigation, therefore, was to compare the perception and prevalence of DH in
      two distinct non-periodontal practice populations, one U.K. and one Korean.
      Completed questionnaires from 557 patients (230 males and 327 females, comprising
      115 males and 162 females, mean age 41.7 years (s.d.=14.36), U.K. and 115 males
      and 165 females, mean age 29.7 years (s.d.=11.86), Korean) were collected.
      Analysis was by frequency distribution and cross-tabulation (Statistical Package
      for the Social Sciences (SPSS)). DH prevalence was similar and at levels
      comparable with those reported previously. Prevalence was higher in the third and
      fourth decades in both populations. Although there were no differences between
      U.K. or Korean males and U.K. or Korean females, there was a significant
      difference between gender reporting of DH, with more females complaining of DH
      than males (standard normal deviation (SND)=4.3, 95% confidence interval
      (CI)=0.1134-0.2736). DH appeared to be regarded by patients as not severe in most
      cases, so treatment was not generally sought. Of those who claimed to have sought
      treatment, a significant number had received restorative treatment. Of those
      patients, only 23.3% of U.K. and <or=2% of Korean patients claimed to have used a
      desensitizing dentifrice. Pain from DH was reported as low grade (slight,
      occasional) occurring over 5 years in both populations. Cold appeared to be the
      most reported stimulus in the two populations. Less periodontal surgery had been
      undertaken in these two populations (12.6% U.K. and 7.1% Korean) compared with
      those referred to a teaching hospital periodontal department (34.5%). This
      compared favourably with previous findings in the general dental population
      (15.5%). Discomfort following hygiene therapy did not appear to last >or=7 days
      in either population. The results indicated that there were no significant
      differences between U.K.- and Korean-based populations in their perception of DH,
      with the exception that more females complained of sensitivity than males in both
      groups. Overall, DH was not considered a major dental problem by most patients in
      either of the populations.

PMID- 11298906
TI  - Fluoride release from glass-ionomer cements, compomers and resin composites.
AB  - The short and long-term fluoride release of 16 products (seven conventional glass
      ionomers, five light-activated glass-ionomers, two polyacid-modified resin
      composites and two resin composites) commercialized as fluoride-releasing
      materials were measured. A potential link between the material type and its level
      of fluoride release was researched. The fluoride release was evaluated after
      different time intervals. Initial fluoride release from all materials was highest
      during the first 24 h and decreased sharply over the first week. Some groups of
      materials appeared to be significantly different after, respectively, 7 and 91
      days. However, it was impossible to correlate the fluoride release of the
      materials by their type (conventional or resin-modified glass-ionomers, polyacid
      modified resin composite and resin composite) except if we compared the products
      from the same manufacturer. The link between fluoride release and an acid-base
      reaction seems to be confirmed. The glass-ionomer composition (glass particles
      and polyacid's type, powder/liquid ratio) should have more influence on fluoride
      release than material type.

PMID- 11298907
TI  - The accuracy with which the human condyle can be expressed in the coordinate
      system of JAWS3D using a unilateral fiducial marker.
AB  - Previous studies have indicated that the selection of condylar referencing points
      can significantly influence condylar point trajectories, and the use of
      radiographically determined condylar points is essential for accurate
      representation of condylar movement. The aim of this investigation was to
      determine the accuracy with which the three-dimensional locations of condylar
      points could be determined in the coordinate system of the JAWS3D tracking device
      when an ipsilateral fiducial marker is used. A perspex mandible containing
      condylar radiographic markers was constructed. A JAWS3D target frame and a
      fiducial marker, supporting radiographic markers, were secured to the perspex
      mandible. The image data from computer tomography scans of the condyles and
      fiducial marker, together with photographs of the fiducial marker and the JAWS3D
      target frame were used to calculate condylar point coordinates in the JAWS3D
      coordinate system. These data were then compared with the data obtained by direct
      measurement of the condylar radiographic markers in the JAWS3D coordinates. The
      results suggest that a unilateral fiducial marker is sufficient to allow the
      registration of ipsilateral condylar point coordinates to an accuracy of
      approximately 1.0 mm.

PMID- 11298908
TI  - A long term study of fluoride release from metal-containing conventional and
      resin-modified glass-ionomer cements.
AB  - The objective of this study was to determine long term release of fluoride from a
      resin-modified glass-ionomer cement (RMGIC) (Fuji II LC (FLC)) compared with that
      from two conventional acid-base setting cements (HiDense (HD) and KetacSilver
      (KS)) marketed for similar restorative purposes. Fluoride release from discs of
      cement immersed in water or artificial saliva was measured for 2.7 years using an
      ion selective electrode technique. The RMGIC was affected by water if immersed
      immediately after setting. This is similar to conventional acid-base cements and
      the experimental method was designed to allow for this. Over the 2.7-year period,
      the RMGIC and HD released similar amounts of fluoride into both water and
      artificial saliva. In water, the RMGIC released the most fluoride, while in
      artificial saliva the highest release was from HD. KS released the least amount
      of fluoride in both immersing liquids. In artificial saliva, release was reduced
      to 17-25% of that found in water, with the RMGIC showing the greatest reduction.
      Both acid-base cured cements showed changes in colour over the 2.7-year span,
      while the colour of the RMGIC was stable. It was concluded that the RMGIC
      released equivalent or greater amounts of fluoride than the two acid-base cure
      glass-ionomers over a period of 2.7 years.

PMID- 11298910
TI  - An appraisal of the literature on centric relation. Part III.
AB  - The literature directly and indirectly related to centric relation (CR) has been
      reviewed chronologically. More than 300 papers and quoted sections of books have
      been divided into three sections. The first two parts are related to CR. Studies
      in this group mainly compared, either the position of the mandibular condyle or
      the mandible itself in different CR recordings. Various tools were discussed for
      this purpose. The third part of the paper is about CR-centric occlusion (CO)
      discrepancy. CR still remains one of the controversial issues in prosthodontics
      and orthodontics. Debates such as mounting casts on the articulator by
      reproducible records for orthodontic treatment planning and end results, and
      whether or not orthodontic treatment based on CO causes TMJ dysfunction, remain
      unsolved. The references are listed at the end of Part III.

PMID- 11298911
TI  - The relation of mandibular laterotrusion with ipsilateral TMJ clicking.
AB  - The purpose of this study was to investigate the association of temporomandibular
      joint (TMJ) clicking with the types of canine guidance, the tracing patterns of
      mandibular laterotrusion and, especially, with the movements of the working side
      condyle. In a young subject group, the movements of left and right mandibular
      laterotrusion were measured at the incisal and the lateral pole point of the
      working side condyle. All samples were divided into one of two groups according
      to the mesial (M) or distal (D) canine guidance. They were also divided into
      protrusive laterotrusion (PL) or retrusive laterotrusion (RL) groups according to
      the tracing patterns. The incidence of clicking was 23.8% in all 84 TMJs. There
      was no significant difference between the M and the D groups. However, clicking
      occurrence was significantly higher in the RL than in the PL group (P<0.05). The
      condyles in clicking joints moved more posterior in ipsilateral laterotrusion
      than the condyles in non-clicking joints. The condyles in RL also moved more
      posterior than those in PL. It is suggested that the posterior movement of the
      working side condyle in RL has a strong relationship with the internal
      derangement of the TMJ. However, it is not related to the type of canine
      guidance.

PMID- 11298909
TI  - Effect of addition of ethyl alcohol on gelation and viscoelasticity of tissue
      conditioners.
AB  - The clinical effectiveness of tissue conditioners is influenced by their gelation
      characteristics and viscoelastic properties after gelation. The purpose of this
      study was to evaluate the effect of addition of ethyl alcohol (EtOH) on these
      properties, and to compare the effect of EtOH with that of the powder/liquid
      (P/L) ratio. Three tissue conditioners were used in this study. The gelation
      times were obtained with an oscillating rheometer. The viscoelastic properties
      after gelation were also evaluated by stress relaxation tests. Addition of
      greater amounts of EtOH produced the shorter gelation time and the larger flow
      after gelation. Conversely, although the use of a higher P/L ratio produced a
      shorter gelation time, this procedure leads to a smaller flow after gelation. The
      results suggested that the addition of EtOH to the liquids of tissue conditioners
      is an effective method for controlling gelation times and viscoelastic properties
      after gelation.

PMID- 11298912
TI  - Bonding agent is a decisive factor in determining the marginal leakage of dental
      composites subjected to thermal cycling: an in vitro study.
AB  - The marginal leakage at the dentine/composite interface in Class II composite
      restorations subjected to thermal cycling has been effectively evaluated using
      the silver staining technique. The presence of a bonding agent at the
      dentine/composite interface is found to improve adhesion. Scanning electron and
      optical microscopic observations of sectioned specimens reveal that applying a
      second coat of bonding agent on the dentinal surface helps in reducing
      microleakage compared to a single coat application, in all three radiopaque
      composite/bonding agent systems studied (Z100/Single Bond, Spectrum TPH/Prime &
      Bond 2.1 and Chitra/Chitrabond 1.0). Thermal cycling during in vitro studies was
      found to provide a more appropriate representation of the adhesive behaviour of
      the composite in clinical situations.

PMID- 11298914
TI  - Adverse effect of dentine bonding agent on the oral mucosa of guinea pigs.
AB  - The purpose of present study was to determine the possibility of nebulous
      discoloration of the oral mucosa of guinea pigs as a result of the application of
      dentine bonding agents. The materials used were the Clearfil Photo Bond (CPB)
      system's mixture agent, universal agent and catalyst agent. Four types of
      experimental catalysts were used. In male albino guinea pigs weighing 300-500 g,
      oral mucosa irritation tests were performed in accordance with the guidelines of
      the Cosmetic, Toiletry and Fragrance Association (CTFA). Macroscopical findings
      on the oral mucosa showed that there was strong nebulous discoloration
      immediately after application of CPB mix and CPB catalyst and throughout the
      experimental periods. However, CPB without 10-methacryloxdecyl dihydrogen
      phosphate (MDP) did not produce noticeable nebulous discoloration and
      inflammation. The CPB mix caused pathological changes, such as paraketosis and
      hyperkeratosis on the endepidermis of the mucosa, immediately after its
      application.

PMID- 11298913
TI  - On-line computerized diagnosis of pain-related disability and psychological
      status of TMD patients: a pilot study.
AB  - Temporomandibular disorders (TMD) is a collective term embracing a number of
      clinical problems, which involve the masticatory musculature, the
      temporomandibular joint or both. Virtually all theories dealing with the
      aetiology and treatment of TMD have recognized the importance of psychological
      factors. This paper reports the development of a computerized on-line program
      (NUS TMD v1.1) for the diagnosis of pain-related disability and psychological
      status of TMD patients based on Axis II of the research diagnostic criteria
      (RDC)/TMD (Dworkin, S.F. & LeResche, L. 1992. Journal of Craniomandibular
      Disorders: Facial Oral Pain, 6, 301), which was developed to redress the lack of
      diagnostic criteria in TMD research. Methods adopted by RDC/TMD for use in
      assessing Axis II status include a seven-item questionnaire for grading chronic
      pain severity, the Symptom Checklist 90 Revised (SCL-90-R) and a jaw disability
      checklist. A pilot study, based on 37 new TMD patient records, was conducted to
      study the pain-related disability and psychological status of TMD patients using
      this newly developed program. The mean age of the predominantly Chinese
      population (86.5%) was 32.19 years (range 20-72 years) with a sex distribution of
      24 females and 13 males. Most patients (78%) had low disability, with 12 patients
      having low intensity and 17 patients having high intensity pain. Approximately
      73% of the sample population were moderately or severely depressed. Patients that
      were moderately and severely depressed had significantly higher scores for
      limitation related to mandibular functioning than normal patients. The three most
      frequent jaw disabilities were: eating hard foods (84%), yawning (78%) and
      chewing (65%).

PMID- 11298915
TI  - Effect of different acid treatments on a porcelain surface.
AB  - The objective of this study was to determine the effect of selected surface
      treatments on the surface texture of a feldspathic porcelain. The three different
      etchant treatments were, acidulated phosphate fluoride (APF) applied for 10 min
      and hydrofluoric acid (HF) applied for 1 and 4 min. After acid treatment, half of
      the specimens from each group were cleansed with water and others were subjected
      to ultrasonic cleaning and then dried. Half of the specimens cleansed with two
      different methods were treated with silane. Scanning electron microscopy (SEM)
      and energy dispersive spectroscopy (EDS) were used to characterize the effects of
      such treatments. Etching with APF displays shallow patterns. Etching for 1 min
      with HF displays deep channels, pores and precipitates on the surface and as the
      etching time increased these channels were replaced by larger channels. EDS
      analyses show that the crystalline precipitates on the etched surfaces, which
      were not readily soluble in water, were the reaction products of Na, K, Ca, Al,
      etc. HF displayed a more roughened surface than the APF gel. However, the
      precipitates remain on the surface after acid application, they can only be
      removed by ultrasonic cleaning and cannot be removed by rinsing.

PMID- 11298916
TI  - Improved bonding of adhesive resin to sintered porcelain with the combination of
      acid etching and a two-liquid silane conditioner.
AB  - This study determined the bond strengths of adhesive resins joined to a
      feldspathic porcelain (VMK 68) for the purpose of developing the most durable
      surface preparation for the porcelain. Three porcelain surfaces-ground, air
      abraded with alumina, and etched with hydrofluoric acid-were prepared. A two
      liquid porcelain conditioner that contained both 4-methacryloyloxyethyl
      trimellitate anhydride (4-META) and a silane coupler (Porcelain Liner M) was used
      as the priming agent. Each of the two liquid components of the conditioner was
      also used individually in order to examine the effects of the respective chemical
      ingredients on adhesive bonding. Two methyl methacrylate (MMA)-based resins
      initiated with tri-n-butylborane (TBB) either with or without 4-META (MMA-TBB and
      4-META/MMA-TBB resins) were used as the luting agents. Shear bond strengths were
      determined both before and after thermocycling. Shear testing results indicated
      that thermocycling was effective for disclosing poor bonding systems, and that
      both mechanical and chemical retention were indispensable for bonding the
      porcelain. Of the combinations assessed, etching with hydrofluoric acid followed
      by two-liquid priming with the Porcelain Liner M material generated the most
      durable bond strength (33.3 MPa) for the porcelain bonded with the 4-META/MMA-TBB
      resin (Super-Bond C&B).

PMID- 11298917
TI  - Assessment of whole saliva flow rate in denture wearing patients.
AB  - It has been suggested that salivary flow rate decreases with age. As is known,
      the presence of a thin salivary film layer is essential for the comfort of the
      mucosa beneath a denture base and for denture retention. The purpose of this
      study was to determine the flow rates, viscosity and the pH of resting and
      stimulated whole saliva before and after prosthetic treatment in complete denture
      wearing patients. Saliva was collected under clinical conditions between 08.00
      and 10.00 hours. The flow rates of whole saliva were measured at three stages:
      (i) resting and stimulated saliva before prosthetic treatment; (ii) immediately
      after the first wearing of the complete denture; and (iii) resting and stimulated
      saliva after 2 or 3 months of wearing the complete denture. Saliva production was
      stimulated by chewing paraffin wax. Flow rate was calculated as collected
      volume/collection time. It was found that there was a significant difference
      between resting and stimulated whole salivary flow rates before and after
      complete denture wearing.

PMID- 11298918
TI  - Synthesis and characterization of the colistin peptide polymyxin E1 and related
      antimicrobial peptides.
AB  - Two strategies were developed to synthesize the acylated cyclic peptides know as
      polymyxins. Synthesis of polymyxin E1 and several analogs enabled us to evaluate
      the minimum inhibitory concentration of individual compounds against Gram
      negative bacteria. In this study we also report the first identification of two
      component peptides in the complex polymyxin fermentation product colistin, a
      Thr2Ser isoform and an acyl group isomer. Both of these peptides, as well as a
      known component peptide, Leu7Ile, were similar to polymyxin E1 in potency,
      suggesting that conservative mutations in the colistin family are functionally
      inconsequential. In contrast, the acyclic analogs of all of these peptides were
      inactive, indicating that the characteristic lariat structure of the polymyxins
      is necessary for antimicrobial activity.

PMID- 11298919
TI  - Monomeric destetrapeptide human insulin from a precursor expressed in
      Saccharomyces cerevisiae.
AB  - Destetrapeptide insulin (DTI, human insulin with B27-30 removed) was obtained
      from a monomeric precursor (MIP) expressed in Saccharomyces cerevisiae through
      tryptic transpeptidation in the presence of synthetic tetrapeptide Gly-Phe-Phe
      Tyr. The in vivo biological activity of DTI, determined by mouse convulsion
      assay, is 22 IU/mg. Its binding activity with insulin receptor on human placental
      membrane is 80% and its in vitro biological activity, determined by free fat cell
      assay, is 77%. Compared with native insulin, DTI molecules do not associate in
      solution but exist in the monomeric form, thus leading to its rapid utilization
      in vivo.

PMID- 11298920
TI  - Pressure monitoring of continuous-flow solid-phase peptide synthesis.
AB  - We describe the noninvasive real-time pressure monitoring of Boc- and Fmoc-based
      peptide synthesis. Pressure was measured using a resistance strain gauge attached
      to the inlet of a continuous-flow reactor of variable volume. In the assembly of
      the 'difficult' polyalanine sequence, it was shown that pressure monitoring can
      reveal structural variations of the peptide-resin, e.g. the onset, development
      and termination of aggregation. This method provided washing minimization that
      favored substantial saving of solvents. The obtained results demonstrated the
      advantage of pressure monitoring over swellographic monitoring.

PMID- 11298921
TI  - Solution structures of the inactivation gate particle peptides of rat brain type
      IIA and human heart sodium channels in SDS micelles.
AB  - The Ile-Phe-Met (IFM) motif located in the Ill-IV linker of voltage-gated sodium
      channels has been identified as a major component of the fast inactivation gate.
      If Gln was substituted for Phe, the role in the gate was disrupted completely. If
      Ile was replaced by Gln inactivation became slightly incomplete and if the Thr,
      which is adjacent to the IFM motif (-IFMT-), was replaced by Met, inactivation
      became much more incomplete than in the I/Q mutation, but not as vigorous as in
      the F/Q mutation. Previously, we studied the structures of the inactivation gate
      related peptide (K1480-K1496 in rat brain type-IIA, MP-3A) and its F1489/Q
      substituted one (MP-4A) in SDS micelles and found that the conformational change
      of the IFM hydrophobic cluster due to the F/Q substitution may be a reason for
      disrupting the gate. In this study, in order to obtain supporting evidence for
      this view and also to further knowledge of the effect of I/Q and T/M mutations on
      the structure of the IFM cluster, we studied the structures of 11488Q [MP(rb)
      3QFMT] and T1491M [MP(rb)-31FMM] substituted peptides. The fragment peptide K1477
      K1493 [MP(hh)-3A] and its T1488M substituted peptide [MP(hh)-3IFMM] in the human
      heart sodium channel were also studied. It was found that the backbone structures
      around the IMF motif of MP-3A, MP(hh)-3A and MP(rb)-3QFMT resemble one another in
      such a manner that the residues Ile(Gln) and Thr are brought so close together
      that they form a unique type of lid to occlude the pore. In contrast, the
      residues between Ile and M1491 of MP(rb)-3IFMM or M1488 of MP(hh)-3IFMM were
      fairly far apart from each other. We conclude that Thr plays an important role in
      forming a structure of the IFM hydrophobic cluster for inactivation.

PMID- 11298923
TI  - Deprotonation of hydrochloride salts of amino acid esters and peptide esters
      using commercial zinc dust.
AB  - The deprotonation of hydrochloride salts of ethyl and methyl esters of amino
      acids and peptides is accomplished using activated zinc dust. The reaction is
      neat and quantitative. Thus, the free amino acid esters and peptide esters have
      been isolated in good yield and purity.

PMID- 11298922
TI  - Structure-activity relationship of [Nphe1]-NC-(1-13)-NH2, a pure and selective
      nociceptin/orphanin FQ receptor antagonist.
AB  - A series of analogs of the ORL1 receptor antagonist [Nphe1]-NC(1-13)-NH2 was
      prepared and tested for agonistic and antagonistic activities in the mouse vas
      deferens, a preparation that shows high sensitivity to nociceptin and related
      peptides. The purpose of this study was to determine the role of the aromatic
      residue at the N-terminal for antagonism and eventually identify compounds with
      improved potency. Results indicated that all 23 compounds are inactive as
      agonists, and the antagonistic potency of the initial template [Nphe1]-NC(1-13)
      NH2 is high (pKB 6.43) compared with those of all other compounds except
      [(S)(betaMe)Nphe1]NC(1-13)-NH2 (pK(B) 6.48). The other 22 compounds can be
      divided into two groups: 10 show antagonistic potencies (pK(B)) ranging from 5.30
      to 5.86, whereas the other 12 compounds are inactive. This study clearly shows
      that the aromatic ring of Nphe is very critical for the interaction with the ORL1
      receptor and can not be enlarged or sterically modified without significant loss
      of antagonistic potency.

PMID- 11298924
TI  - A peptide derived from the C-terminal part of a plant cysteine protease folds
      into a stack of two beta-hairpins, a scaffold present in the emerging family of
      granulin-like growth factors.
AB  - A 35 amino acid residue peptide corresponding to the N-terminal subdomain of the
      granulin-like repeat from rice oryzain beta was synthesized and regioselectively
      oxidized to produce a species with a [1-3, 2-4] disulfide-pairing pattern. The
      resulting peptide was studied in solution using NMR and was shown to adopt the
      tertiary topology of a stack of two beta-hairpins found in the emerging family of
      granulin-like growth factors. Because of the longer second beta-hairpin, the
      overall conformation of the peptide is somewhat more flexible than that of its
      well-structured carp granulin-1 analog. Except for the cysteine alignment, there
      is very little sequence homology between granulin-like growth factors from the
      animal kingdom and the granulin-like repeats at the C-termini of plant cysteine
      proteases. Therefore, the stack of two beta-hairpins may be a conserved three
      dimensional organization of the granulin-like repeats from evolutionary distant
      sources with a significant role in specific protein-protein interactions.

PMID- 11298925
TI  - The leucine zipper motif of the envelope glycoprotein ectodomain of human
      immunodeficiency virus type 1 contains conformationally flexible regions as
      revealed by NMR and circular dichroism studies in different media.
AB  - A 43-mer peptide derived from the coiled coil domain of the transmembrane
      glycoprotein, gp41, of human immunodeficiency virus type 1, was synthesized.
      Light scattering measurements suggested that the peptide molecules likely exist
      in the aqueous solution in trimeric form. Circular dichroism experiments showed a
      moderate helix population enhancement for the peptide in 80% methanol solution
      relative to helicity in sodium dodecyl sulfate micellar suspension. NMR
      spectroscopy indicated that the N-terminal section of the peptide was
      conformationally more sensitive to the medium. The conformationally labile
      regions contain residues implicated in gp41-gp120 association. Our data support
      the idea that the coiled coil region is responsible for oligomerization of the
      gp41 ectodomain and suggest a site of conformational isomerization following
      receptor binding-induced gp120 dissociation from gp41.

PMID- 11298926
TI  - A novel bovine lactoferrin peptide, FKCRRWQWRM, suppresses Candida cell growth
      and activates neutrophils.
AB  - To identify potent new antifungal agents, the Candida cell growth inhibitory
      activities of six lactoferrin (Lf) peptides consisting of 6-25 amino acid
      residues (peptide 1, FKCRRWQWRMKKLGAPSITCVRRAF lactoferricin B; peptide 2,
      FKCRRWQWRM; peptide 2', FKARRWQWRM; peptide 3, GAPSITCVRRAF; peptide 4, RRWQWR;
      and peptide 5, RWQWRM) were examined. Of these, peptide 2 strongly suppressed the
      multiplication of Candida cells, but other peptides showed only weak activities.
      In two strains of C. albicans, the minimum inhibitory concentration 100 of
      peptide 2 (17.3+/-2.2 microM and 17.5+/-2.4 microM) was close to that of
      miconazole (13.0+/-1.7 microM and 13.1+/-1.6 microM) but markedly different from
      that of amphotericin B (0.52+/-0.09 microM and 0.56+/-0.11 microM). The
      suppression of Candida cell growth was additively increased by a combination of
      peptide 2 with amphotericin B and miconazole. Peptides 1, 3, 4 and 5 and Lf
      suppressed iron uptake by Candida cells, inversely correlated with their Candida
      cell growth inhibition activities. However, iron uptake was not inhibited by
      peptide 2. In addition, peptide 2 upregulated Candida cell killing activity of
      polymorphonuclear leukocytes (PMN) increasing their superoxide generation,
      protein kinase C activity, p38 MAPK activity and the expression of p47phox. These
      results indicated that the main antimicrobial activity of the Lf peptides is
      dependent on the N-terminal half of Lf and that the PMN upregulatory activity of
      peptide 2 and additive function of peptide 2 with antifungal drugs are useful for
      prophylaxis and control of candidiasis.

PMID- 11298927
TI  - Preparation of 'side-chain-to-side-chain' cyclic peptides by Allyl and Alloc
      strategy: potential for library synthesis.
AB  - Automated and manual deprotection methods for allyl/allyloxycarbonyl
      (Allyl/Alloc) were evaluated for the preparation of side-chain-to-side-chain
      cyclic peptides. Using a standard Allyl/Alloc deprotection method, a small
      library of cyclic peptides with lactam bridges (with seven amino acids) was
      prepared on an automatic peptide synthesizer. We demonstrate that the Guibe
      method for removing Allyl/Alloc protecting groups under specific neutral
      conditions [Pd(PPh3)4/PhSiH3)/DCM] can be a useful, efficient and reliable method
      for preparing long cyclic peptides on a resin. We have also manually synthesized
      a cyclic glucagon analogue containing 24 amino acid residues. These results
      demonstrated that properly controlled palladium-mediated deprotection of
      Allyl/Alloc protecting groups can be used to prepare cyclic peptides on the resin
      using an automated peptide synthesizer and cyclic peptides with a long chain.

PMID- 11298928
TI  - Temporal temperature gradient gel electrophoresis (TTGE) as a tool for
      identification of Lactobacillus casei, Lactobacillus paracasei, Lactobacillus
      zeae and Lactobacillus rhamnosus.
AB  - AIMS: To develop a tool for rapid and inexpensive identification of the
      Lactobacillus casei complex. METHODS AND RESULTS: Lactobacillus casei,
      Lactobacillus paracasei, Lactobacillus zeae and Lactobacillus rhamnosus were
      identified by PCR-amplification of the segment between the U1 and U2 regions of
      16S rDNA (position 8-357, Escherichia coli numbering) and temporal temperature
      gradient gel electrophoresis (TTGE). Seven tested Lact. paracasei strains were
      divided into three TTGE-subgroups. CONCLUSION: TTGE successfully distinguished
      between the closely-related target species. TTGE is also a powerful method for
      revealing sequence heterogeneities in the 16S rRNA genes. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Due to rapid and easy performance, TTGE of PCR-amplified 16S rDNA
      fragments will be useful for the identification of extended numbers of isolates.

PMID- 11298929
TI  - In vitro activity of propyl gallate-azole drug combination against fluconazole-
      and itraconazole-resistant Candida albicans strains.
AB  - AIMS: The influence of an antioxidant, propyl gallate (PG), on the in vitro
      antifungal activity of itraconazole and fluconazole, was investigated to
      determine whether PG could increase the antifungal activity and reduce strain
      resistance. METHODS AND RESULTS: Susceptibility tests were performed against
      azole-resistant isolates of Candida albicans by the microbroth dilution method in
      the presence of PG at 400 microg ml-1. PG-triazole combination brought about a
      marked reduction of inhibitory azole concentration. In particular, the MIC90 for
      itraconazole and fluconazole dropped from 1 microg ml-1 to 0.125 microg ml-1 and
      from > 64 microg ml-1-8 microg ml-1, respectively. CONCLUSION: It is likely that
      more than one mechanism is involved in the above synergistic interaction,
      including effects of PG on ATP synthesis, thus reducing the ABC transporters
      activity, or an effect on the target of azole, i.e. the P-450 cytochrome.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The PG-triazole combination may have a role
      in future topical antifungal strategies but other studies are warranted.

PMID- 11298930
TI  - Comparison of fermentative capacities of industrial baking and wild-type yeasts
      of the species Saccharomyces cerevisiae in different sugar media.
AB  - AIMS: To compare the fermentative capacity of wild and domesticated isolates of
      the genus Saccharomyces. METHODS AND RESULTS: The fermentative capacity of yeasts
      from a variety of wild and domesticated sources was tested in synthetic dough
      media that mimic major bread dough types. Domesticated yeast strains were found
      to have better maltose-utilizing capacity than wild yeast strains. The capacity
      to ferment sugars under high osmotic stress was randomly distributed amongst wild
      and baking strains of Saccharomyces. CONCLUSION: The domestication of bakers'
      yeast has enhanced the ability of yeasts to ferment maltose, without a similar
      impact on the fermentative capacity under high osmotic conditions. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study, combined with molecular studies of both wild
      and domesticated yeast, showed that domestication of bakers' yeast has resulted
      in improved maltose utilization, apparently via the duplication and mutation of
      the MAL genes.

PMID- 11298931
TI  - In vitro stability and expression of green fluorescent protein under high
      pressure conditions.
AB  - AIMS: The objective of this work was to evaluate the use of wild-type GFP and
      mutant forms thereof as reporter for gene expression under high pressure
      conditions. METHODS AND RESULTS: The intensity of fluorescence after high
      pressure treatment was checked by subjecting cells, crude protein extracts
      containing GFPs and purified GFPs to pressures ranging from 100 MPa to 900 MPa.
      All tested GFP's retained fluorescence up to 600 MPa without loss of intensity.
      Expression of GFP under sublethal conditions was investigated in Escherichia coli
      with plasmid pQBI63, in which rsGFP is placed downstream of the T7 RNA polymerase
      binding site. T7 RNA polymerase is controlled in E. coli BL21 (DE3) pLysS by an
      IPTG inducible lacUV5 promoter. A pressure induced increase of GFP expression was
      monitored at 50 Mpa and 70 MPa. CONCLUSION: Fluorescence of GFPs is not
      influenced at pressures at which protein expression still occurs. We showed that
      the expression system used is inducible by pressurized conditions. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study proved GFP to be a suitable reporter for gene
      expression studies capable to detect pressure induced gene expression.

PMID- 11298932
TI  - Purification and N-terminal amino acid sequence of fructose-6-phosphate
      phosphoketolase from Bifidobacterium longum BB536.
AB  - AIMS: The key enzyme in the fructose-6-phosphate shunt in bifidobacteria,
      Fructose-6-phosphate phosphoketolase (F6PPK; E.C. 4.1.2.22.), was purified to
      electrophoretic homogeneity for the first time from Bifidobacterium longum
      (BB536). METHODS AND RESULTS: A three-step procedure comprising acetone
      fractionation followed by fast protein liquid chromatography (FPLC) resulted in a
      30-fold purification. The purified enzyme had a molecular mass of 300 +/- 5 kDa
      as determined by gel filtration. It is probably a tetramer containing two
      different subunits with molecular masses of 93 +/- 1 kDa and 59 +/- 0.5 kDa, as
      determined by SDS-PAGE. CONCLUSION: The deduced N-terminal amino acid sequences
      of the two subunits revealed no significant similarity between them and other
      proteins when compared to the data bases of EMBL and SWISS-PROT, indicating that
      this could be the first report on N-terminal amino acid sequence of F6PPK.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The data from this study will be used to
      design oligonucleotide probe specific for bifidobacteria and to study the gene
      encoded F6PPK.

PMID- 11298933
TI  - Mycotoxin production from fungi isolated from grapes.
AB  - AIMS: In order to assess the potential for producing mycotoxins, fungi were
      isolated from wine producing grapes. METHODS AND RESULTS: The isolates were
      identified and Penicillium expansum, the most well recognized mycotoxin producer,
      was analysed for mycotoxin production by TLC. Many of the strains produced
      patulin and/or citrinin, often depending on whether they were grown on a grape or
      yeast extract sucrose media. CONCLUSION: Citrinin was produced by all strains
      grown in the yeast extract sucrose medium, but only one strain (from 51) was able
      to produce this compound in grape juice medium. Patulin was produced in the yeast
      extract medium by 20 strains and in grape juice medium by 33 strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of mycotoxins in wine
      producing grapes is discussed. Grapes contamination with patulin seems not to
      contribute to wine contamination, and no ochratoxin producing fungi was
      identified.

PMID- 11298934
TI  - Thuricin 7: a novel bacteriocin produced by Bacillus thuringiensis BMG1.7, a new
      strain isolated from soil.
AB  - AIMS: Detection and identification of new antagonistic activities towards
      Bacillus cereus and relatives. METHODS AND RESULTS: Twenty Bacillus thuringiensis
      strains were screened for their capacity to express bacteriocin-like agents.
      Strain BMG1.7, isolated from soil, showed an antagonistic activity called
      thuricin 7. Thuricin 7 was active against several species of the genus Bacillus,
      including three of the four known B. thuringiensis/B. cereus bacteriocin
      producers, as well as against Streptococcus pyogenes and Listeria monocytogenes
      strains. Antimicrobial activity was lost after treatment with proteinase K. The
      active protein had an apparent molecular weight of 11.6 kDa, and was secreted at
      the end of the exponential growth phase. Thuricin 7 retained 55% of the activity
      after incubation at 98 degrees C for 30 min. The mode of action of thuricin 7 was
      shown to be bactericidal and bacteriolytic. CONCLUSION: Thuricin 7 is a novel
      bacteriocin produced by a newly isolated Bacillus thuringiensis strain BMG1.7.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The characteristics of thuricin 7 indicate
      that it is a new bacteriocin which may have interesting biotechnological
      applications due to its relatively large activity spectrum.

PMID- 11298935
TI  - Improvement of xylitol production by Candida guilliermondii FTI 20037 previously
      adapted to rice straw hemicellulosic hydrolysate.
AB  - AIMS: To evaluate a simple and economical technique to improve xylitol production
      using concentrated xylose solutions prepared from rice straw hemicellulosic
      hydrolysate. METHODS AND RESULTS: Experiments were carried out with rice straw
      hemicellulosic hydrolysate containing 90 g l-1 xylose, with and without the
      addition of nutrients, using the yeast Candida guilliermondii previously grown on
      the hydrolysate (adapted cells) or on semi-defined medium (unadapted cells). By
      this method, the yield of xylitol increased from 17 g l-1 to 50 g l-1, and xylose
      consumption increased from 52% to 83%, after 120 h of fermentation. The xylitol
      production rates were very close to that (0.42 g l-1 h-1) attained in a medium
      simulating hydrolysate sugars. CONCLUSION: Yeast strain adaptation to the
      hydrolysate showed to be a suitable method to alleviate the inhibitory effects of
      the toxic compounds. Adapted cells of Candida guilliermondii can efficiently
      produce xylitol from hydrolysate with high xylose concentrations. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Yeast adaptation helps the bioconversion process in
      hydrolysate made from lignocellulosic materials. This low-cost technique provides
      an alternative to the detoxification methods used for removal of inhibitory
      compounds. In addition, the use of adapted inocula makes it possible to schedule
      a series of batch cultures so that the whole plant can be operated almost
      continuously with a concomitant reduction in the overall operation time.

PMID- 11298936
TI  - Role of batch depletion of broiler houses on the occurrence of Campylobacter spp.
      in chicken flocks.
AB  - AIMS: The effect of batch depletion of broiler houses for campylobacter
      occurrence in broiler flocks was estimated in 10 flocks, each comprising a
      separate female and male batch. METHODS AND RESULTS: The chicks were sampled
      first by cloacal swabs in the broiler houses before the start of the depopulation
      and secondly, on arrival at the abattoir. Females were slaughtered at 5 weeks of
      age, males at 6 weeks. The number of campylobacter-positive batches increased
      from five to seven female batches, and from five to 10 male batches, between the
      two sampling rounds. CONCLUSION: It is concluded that batch depletion of broiler
      houses increased the prevalence of Campylobacter spp.-infected broilers in the
      flocks, that the introduction occurred when catching the first batch, and that
      campylobacter spreads through the entire flock within a week. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The results from this study emphasize the need to manage
      depopulation of broiler houses as quickly as possible and in one batch only.

PMID- 11298937
TI  - Intracellular nickel accumulation by Pseudomonas aeruginosa and its chemical
      nature.
AB  - AIMS: To investigate intracellular localization of nickel and its chemical nature
      in Pseudomonas aeruginosa. METHODS AND RESULTS: Transmission electron micrographs
      of Ni-loaded bacteria exhibited a darkened electron opaque zone throughout the
      cell periphery. Energy dispersive X-ray analysis confirmed the deposition of
      metallic nickel. Cell fractionation revealed that 88% of the accumulated nickel
      was restricted to the periplasm and membrane. X-ray diffraction patterns
      ascertained the chemical nature of cellular Ni as phosphide (Ni5P4, NiP2 and
      Ni12P5) and carbide (Ni3C) crystals. CONCLUSION: Pseudomonas aeruginosa
      accumulated nickel as its phosphide and carbide crystal mostly in the cell
      envelope region, indicating the predominant role of phosphoryl and
      carboxyl/carbonyl groups of cell wall/membrane components in cation
      sequestration. SIGNIFICANCE AND IMPACT OF THE STUDY: The data contribute
      significantly to a better understanding of bacteria-metal interaction and will be
      useful in developing biotechnological strategies for toxic metal bioremediation.

PMID- 11298938
TI  - Shifting the biotransformation pathways of L-phenylalanine into benzaldehyde by
      Trametes suaveolens CBS 334.85 using HP20 resin.
AB  - AIMS: The biotransformation of L-phenylalanine into benzaldehyde (bitter almond
      aroma) was studied in the strain Trametes suaveolens CBS 334.85. METHODS AND
      RESULTS: Cultures of this fungus were carried out in the absence or in the
      presence of HP20 resin, a highly selective adsorbent for aromatic compounds. For
      the identification of the main catabolic pathways of L-phenylalanine, a control
      medium (without L-phenylalanine) was supplemented with each of the aromatic
      compounds, previously detected in the culture broth, as precursors. Trametes
      suaveolens CBS 334.85 was shown to biosynthesize benzyl and p-hydroxybenzyl
      derivatives, particularly benzaldehyde, and large amounts of 3-phenyl-1-propanol,
      benzyl and p-hydroxybenzyl alcohols as the products of both cinnamate and
      phenylpyruvate pathways. CONCLUSION: The addition of HP20 resin, made it possible
      to direct the catabolism of L- phenylalanine to benzaldehyde, the desired target
      compound, and to trap it before its transformation into benzyl alcohol. In these
      conditions, benzaldehyde production was increased 21-fold, from 33 to 710 mg l-1
      corresponding to a molar yield of 31%. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These results showed the good potential of Trametes suaveolens as a
      biotechnological agent to synthesize natural benzaldehyde which is one of the
      most important aromatic aldehydes used in the flavour industry.

PMID- 11298939
TI  - Detection and characterization of filterable heterotrophic bacteria from rural
      groundwater supplies.
AB  - AIMS: The chemical/physical environment of groundwater may contribute to the
      existence of a subpopulation of small-sized bacteria (filterable bacteria) that
      fails to be trapped on conventional 0.45 microm-pore-size membrane filters during
      routine bacteriological water quality analyses. Efforts were directed to
      determining an efficient recovery method for detection of such cells. METHODS AND
      RESULTS: Individual groundwater supplies in a rural setting were examined by a
      double membrane filtration procedure to determine the presence of heterotrophic
      plate count (HPC) bacteria capable of escaping detection on conventional pore
      size (0.45 microm) membrane filters but retained on 0.22 microm-pore-size
      filters. Since optimum cultural conditions for recovery of filterable bacteria
      are not well defined, initial efforts focused on evaluation of various media
      (R2A, m-HPC and NWRI) and incubation temperatures (15, 20, 28 and 35 degrees C)
      for specific recovery of filterable bacteria. Maximum recovery of small-sized HPC
      bacteria occurred on low-nutrient concentration R2A agar incubated for 7 d at 28
      degrees C. Similarly, identical cultural conditions gave enhanced detection of
      the general HPC population on 0.45 microm-pore-size filters. A 17-month survey of
      10 well water supplies conducted with the cultural conditions described above
      resulted in detection of filterable bacteria (ranging in density from 9 to 175
      cfu ml-1) in six of the groundwater sources. The proportion of filterable
      bacteria in any single sample never exceeded 10% of the total HPC population. A
      majority of the colonies appearing on the 0.22 microm membrane filters was
      pigmented (50-90%), whereas the proportion of colonies demonstrating pigmentation
      on the larger porosity filters failed to exceed 50% for any of the samples (19
      49%). CONCLUSION: A reliable recovery method was developed for the detection of
      filterable bacteria from groundwater. During a subsequent survey study using this
      procedure, filterable bacteria were detected in a majority of the groundwater
      supplies examined; however, the density of filterable bacteria in any single
      sample never exceeded 10% of the total HPC population. Identification of randomly
      selected isolates obtained on the 0.22 microm filters indicated that some of
      these filterable bacteria have been implicated as opportunistic pathogens.
      SIGNIFICANCE AND IMPACT OF THE STUDY: We have determined the presence of small
      sized HPC bacteria in ground water that may go undetected when using standard
      porosity membrane filters for water quality analyses. Further study is needed to
      assess the significance and possible health risk associated with presence of
      filterable bacteria in drinking water supplies from groundwater sources.

PMID- 11298940
TI  - A rapid method to screen degradation ability in chlorophenoxyalkanoic acid
      herbicide-degrading bacteria.
AB  - AIMS: An agar medium containing a range of related chlorophenoxyalkanoic acid
      herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D), 2-methyl-4
      chlorophenoxyacetic acid (MCPA), racemic mecoprop, (R)-mecoprop and racemic 2,4
      DP (2-(2,4-dichlorophenoxy) propionic acid) was developed to assess the catabolic
      activity of a range of degradative strains. METHODS AND RESULTS: The medium was
      previously developed containing 2,4-D as a carbon source to visualise degradation
      by the production of dark violet bacterial colonies. Strains isolated on mecoprop
      were able to degrade 2,4-D, MCPA, racemic mecoprop, (R)-mecoprop and racemic 2,4
      DP, whereas the 2,4-D-enriched strains were limited to 2,4-D and MCPA as carbon
      sources. Sphingomonas sp. TFD44 solely degraded the dichlorinated compounds, 2,4
      D, racemic 2,4-DP and 2,4-DB (2,4-dichlorophenoxybutyric acid). However,
      Sphingomonas sp. AW5, originally isolated on 2,4,5-T, was the only strain to
      degrade the phenoxybutyric compound MCPB (4-chloro-2-methylphenoxybutyric acid).
      CONCLUSION: This medium has proved to be a very effective and rapid method for
      screening herbicide degradation by bacterial strains. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This method reduces the problem of assessing the biodegradability of
      this family of compounds to an achievable level.

PMID- 11298941
TI  - Inhibitory effect of acetosyringone on two aflatoxin biosynthetic genes.
AB  - AIMS: The objective of this study was to determine if acetosyringone affected the
      expression of aflatoxin biosynthetic genes. METHODS AND RESULTS: Two genes, nor1
      and ver1, representing genes whose products are involved in early and late steps
      in aflatoxin biosynthesis, were examined. Two GUS (beta-glucuronidase) reporter
      constructs, nor1:GUS (pGAP12) and ver1:GUS (pGAP13), were used to study the
      effect of acetosyringone on expression of aflatoxin biosynthetic (AF) genes, nor1
      and ver1. The product of nor1 is involved in the formation of norsolorinic acid,
      the first stable intermediate in the aflatoxin pathway. The ver1 gene codes for
      the enzyme catalyzing the formation of demethylsterigmatocystin, an intermediate
      late in the AF pathway. GUS activities of these two reporter constructs were
      inhibited by 80% in the presence of 2 m mol l-1 acetosyringone. CONCLUSION:
      Aflatoxin production in a toxigenic strain 42-12 was also shown to be inhibited
      by acetosyringone to the same level. The levels of inhibition in aflatoxin
      production and gene transcription are congruous in these three strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Recent studies have indicated that some
      phenolics act as signal molecules in plant microbial interactions. Concentration
      of acetosyringone is shown to increase about ten fold when certain metabolically
      active plant tissues are wounded. The knowledge gained can be applied to develop
      strategies in plant breeding programs. The compound may be useful for studying
      molecular mechanism of modulating aflatoxin biosynthesis.

PMID- 11298942
TI  - The role of L-carnitine and glycine betaine in the survival and sub-lethal injury
      of non-growing Listeria monocytogenes cells during chilled storage.
AB  - AIMS: To determine the role played by previous growth in the presence of
      osmolytes on the subsequent survival and sub-lethal injury of L. monocytogenes
      during long-term chilled storage in a model buffer system. METHODS AND RESULTS:
      Four Listeria monocytogenes strains were grown separately to stationary phase in
      Listeria minimal medium (DM) alone or in DM with 4% NaCl alone, or both these
      media supplemented with 1 mM L-carnitine and/or 1 mM glycine betaine. Cells were
      resuspended in phosphate buffered saline (pH 5.5) and stored for four weeks at 4
      degrees C. Initially, and at weekly intervals, samples were plated on both
      Tryptic Soy Agar and Tryptic Soy Agar with 4% NaCl to determine total numbers and
      degree of sub-lethal injury in the populations. The numbers of cells within all
      strains after growth to stationary phase, except one which increased (
      approximately 2 log cfu ml-1, P < 0.05) in the presence of NaCl, were not
      influenced significantly by previous growth conditions (P > 0.05). During
      subsequent chilled storage, however, numbers of all strains grown in the presence
      of NaCl remained constant while those grown in its absence decreased. The rate
      and magnitude of the decrease in cell numbers was strain dependent. The initial
      percentage of sub-lethal injury increased significantly in all strains when grown
      previously in the presence of L-carnitine (P < 0.05). During subsequent chilled
      storage sub-lethal injury increased for all strains in a manner that was strain
      dependent, but not related to the previous growth conditions. CONCLUSION:
      Previous growth in the presence of osmolytes of NaCl, but not osmolytes alone,
      increases the subsequent survival, but not percentage sub-lethal injury, of L.
      monocytogenes during subsequent chilled storage in buffer. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study shows that risks associated with L. monocytogenes
      in chilled food may be influenced by the individual life histories of the cells.

PMID- 11298943
TI  - Anti-proliferative effect of two lactic acid bacteria strains of human origin on
      the growth of a myeloma cell line.
AB  - AIMS: Twenty lactic acid bacteria strains were isolated from human faeces and
      tested by MTT assay for stimulation or inhibition of the proliferation of Vero
      and myeloma cells. METHODS AND RESULTS: None of the strains significantly
      affected the proliferation of Vero cells. However, two isolates (HN1 and HA8)
      showed a strong inhibition of myeloma cell proliferation (16.7 and 5.0%,
      respectively) by MTT assay. CONCLUSION: Both strains have an anti-proliferative
      effect on a tumoral cell line. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      beneficial effect of LAB cancer therapy has been linked to their ability for
      immunomodulation.

PMID- 11298944
TI  - Molecular ecology of social behaviour: analyses of breeding systems and genetic
      structure.
AB  - Molecular genetic studies of group kin composition and local genetic structure in
      social organisms are becoming increasingly common. A conceptual and mathematical
      framework that links attributes of the breeding system to group composition and
      genetic structure is presented here, and recent empirical studies are reviewed in
      the context of this framework. Breeding system properties, including the number
      of breeders in a social group, their genetic relatedness, and skew in their
      parentage, determine group composition and the distribution of genetic variation
      within and between social units. This group genetic structure in turn influences
      the opportunities for conflict and cooperation to evolve within groups and for
      selection to occur among groups or clusters of groups. Thus, molecular studies of
      social groups provide the starting point for analyses of the selective forces
      involved in social evolution, as well as for analyses of other fundamental
      evolutionary problems related to sex allocation, reproductive skew, life history
      evolution, and the nature of selection in hierarchically structured populations.
      The framework presented here provides a standard system for interpreting and
      integrating genetic and natural history data from social organisms for
      application to a broad range of evolutionary questions.

PMID- 11298945
TI  - Differences in population structure of the anther smut fungus Microbotryum
      violaceum on two closely related host species, Silene latifolia and S. dioica.
AB  - We investigated the genetic population structure of the sexually transmitted
      plant pathogen, the fungus Microbotryum violaceum, on the two closely related
      host species Silene latifolia and S. dioica using microsatellite markers. We
      found strong deviations from Hardy-Weinberg expectations, with significant
      heterozygote deficiency in almost all populations. Fungal strains from the two
      host species were differentiated, and these host races differed in amount of
      variation within populations and differentiation among populations. Anther smut
      from S. latifolia harboured significantly less microsatellite diversity and were
      more genetically differentiated from each other than those from S. dioica. Small
      effective population sizes, rapid population turnover, and less gene flow among
      populations could lead to this higher population differentiation and lower within
      population genetic diversity for anther smut populations on S. latifolia than on
      S. dioica. These results are in concordance with host ecology because S.
      latifolia grows in more disturbed habitats than S. dioica and may provide a
      shorter-lived host environment.

PMID- 11298946
TI  - Population genetic structure of the lemon shark (Negaprion brevirostris) in the
      western Atlantic: DNA microsatellite variation.
AB  - DNA microsatellite markers were used to characterize the population genetic
      structure of the lemon shark, Negaprion brevirostris, in the western Atlantic.
      This study demonstrates for the first time the usefulness of microsatellites to
      study population genetic structure and mating systems in the Chondricthyes. Lemon
      sharks (mostly juveniles) were sampled non-destructively from four locations,
      Gullivan Bay and Marquesas Key in Florida, Bimini, Bahamas, and Atol das Rocas,
      Brazil. At least 545 individuals were genotyped at each of four dinucleotide
      loci. The number of alleles per locus ranged from 19 to 43, and expected
      heterozygosities ranged from 0.69 to 0.90. Relatively little genetic structure
      was found in the western Atlantic, with small but significant values for
      estimators of F(ST) and R(ST) among populations, theta (0.016) and rho (0.026),
      respectively. No sharp discontinuities were found between the Caribbean sites and
      Brazil, and most alleles were found at all four sites, indicating that gene flow
      occurs throughout the western Atlantic with no evidence for distinct stocks.

PMID- 11298947
TI  - Detection of reduction in population size using data from microsatellite loci.
AB  - We demonstrate that the mean ratio of the number of alleles to the range in
      allele size, which we term M, calculated from a population sample of
      microsatellite loci, can be used to detect reductions in population size. Using
      simulations, we show that, for a general class of mutation models, the value of M
      decreases when a population is reduced in size. The magnitude of the decrease is
      positively correlated with the severity and duration of the reduction in size. We
      also find that the rate of recovery of M following a reduction in size is
      positively correlated with post-reduction population size, but that recovery
      occurs in both small and large populations. This indicates that M can distinguish
      between populations that have been recently reduced in size and those which have
      been small for a long time. We employ M to develop a statistical test for recent
      reductions in population size that can detect such changes for more than 100
      generations with the post-reduction demographic scenarios we examine. We also
      compute M for a variety of populations and species using microsatellite data
      collected from the literature. We find that the value of M consistently predicts
      the reported demographic history for these populations. This method, and others
      like it, promises to be an important tool for the conservation and management of
      populations that are in need of intervention or recovery.

PMID- 11298948
TI  - Genetic diversity and introgression in the Scottish wildcat.
AB  - This paper describes a genetic analysis of wild-living cats in Scotland. Samples
      from 230 wild-living Scottish cats (including 13 museum skins) and 74 house cats
      from England and Scotland were surveyed for nine microsatellite loci. Pelage
      characteristics of the wild-living cats were recorded, and the cats were then
      grouped into five separate categories depending on the degree to which they
      conformed to the characteristics attributed to Felis silvestris Schreber, 1775.
      Allele frequency differences between the morphological groups are greater than
      those among the three house cat samples. Analysis of genetic distances suggests
      that more of the differences between individuals can be explained by pelage than
      geographical proximity, and that pelage and geographical location are not
      confounded. Ordination of the genetic distances suggests two main groups of wild
      living cats, with intermediates, and one group is genetically very similar to the
      house cats, while the other group contains all cats taxonomically identified as
      wildcat based on morphology. A genetic mixture analysis gives similar results to
      the ordination, but also suggests that the genotypes of a substantial number of
      cats in the wildcat group are drawn from a gene pool with genotypes in
      approximately equilibrium proportions. We argue that this is evidence that these
      cats do not have very recent domestic ancestry. However, from the morphological
      data it is highly likely that this gene pool also contains a contribution from
      earlier introgression of domestic cat genes.

PMID- 11298949
TI  - Genetic structure of North American wolverine (Gulo gulo) populations.
AB  - Wolverines (Gulo gulo) are found in low densities throughout their circumpolar
      distribution. They are also potentially susceptible to human-caused population
      fragmentation (development, recreation and fur harvesting). The combination of
      these factors has contributed to this species being listed as having either
      vulnerable or endangered status across much of its current range. The effects of
      inherently low densities and anthropogenic pressures on the genetic structure and
      variation of wolverine populations are, as yet, unknown. In this study, 461
      individuals were typed at 12 microsatellite loci to investigate the population
      genetic structure of wolverines from north-western Alaska to eastern Manitoba.
      Levels of gene flow and population differentiation among the sampled regions were
      estimated via a genotype assignment test, pairwise F(ST), and two genetic
      distance measures. Our results suggest that wolverine populations from
      southernmost regions, in which anthropogenic factors are strongest, revealed more
      genetic structuring than did northern populations. Furthermore, these results
      suggest that reductions in this species' range may have led to population
      fragmentation in the extreme reaches of its southern distribution. The continued
      reduction of suitable habitat for this species may lead to more populations
      becoming isolated remnants of a larger distribution of northern wolverines, as
      documented in other North American carnivore species.

PMID- 11298950
TI  - Population genetic structure of the endangered tropical tree species Caryocar
      brasiliense, based on variability at microsatellite loci.
AB  - We report the population genetic structure of the endangered tropical tree
      species Caryocar brasiliense, based on variability at 10 microsatellite loci.
      Additionally, we compare heterozygosity and inbreeding estimates for continuous
      and fragmented populations and discuss the consequences for conservation. For a
      total of 314 individuals over 10 populations, the number of alleles per locus
      ranged from 20 to 27 and expected and observed heterozygosity varied from 0.129
      to 0.924 and 0.067 to 1.000, respectively. Significant values of theta and R(ST)
      showed important genetic differentiation among populations. theta was much lower
      than R(ST), suggesting that identity by state and identity by descent have
      diverged in these populations. Although a significant amount of inbreeding was
      found under the identity by descent model (f = 0.11), an estimate of inbreeding
      for microsatellite markers based on a more adequate stepwise mutation model
      showed no evidence of nonrandom mating (R(IS) = 0.04). Differentiation (pairwise
      F(ST)) was positively correlated with geographical distance, as expected under
      the isolation by distance model. No effect of fragmentation on heterozygosity or
      inbreeding could be detected. This is most likely due to the fact that Cerrado
      fragmentation is a relatively recent event (approximately 60 years) compared to
      the species life cycle. Also, the populations surveyed from both fragmented and
      disturbed areas were composed mainly of adult individuals, already present prior
      to ecosystem fragmentation. Adequate hypothesis testing of the effect of habitat
      fragmentation will require the recurrent analysis of juveniles across generations
      in both fragmented and nonfragmented areas.

PMID- 11298951
TI  - Resistance or emigration: response of the high-alpine plant Eritrichium nanum
      (L.) Gaudin to the ice age within the Central Alps.
AB  - Two main possibilities regarding glacial survival of the mountain flora of the
      Alps during the Quaternary have been discussed: the tabula rasa and the nunatak
      hypotheses. Eritrichium nanum (L.) Gaudin (Boraginaceae) is a perennial cushion
      plant, occurring at high elevations of the Central Alps and having a preference
      for extreme habitats. It belongs to a group of high-alpine plants, for which in
      situ glacial survival on nunataks is ecologically possible. By investigating 20
      populations of E. nanum of potential nunatak and peripheral refugial regions
      using amplified fragment length polymorphism, considerable genetic differences
      between populations from the Central Alps and populations from peripheral refugia
      were detected; hence, the latter probably did not serve as potential sources for
      the re-colonization of the Central Alps after glaciation. Genetic variation was
      hierarchically structured (AMOVA), and three genetically distinct regions could
      be identified in the Central Alps. Two of these, the Penninic and Rhaetic Alps,
      correspond to nunatak regions proposed in the biogeographic literature.
      Populations from the Lepontic Alps formed a third genetic group. Genetic
      correlation (Mantel statistics) was highest within populations, with a modest
      decline among populations within specific nunatak regions and a negative
      correlation outside the genetic influence of specific nunatak regions. In situ
      glacial survival in E. nanum could be a model for the Quaternary history of other
      alpine plants, especially those that also occur at high elevations and in similar
      habitats.

PMID- 11298952
TI  - Colonization, extinction, and phylogeographic patterning in a freshwater
      crustacean.
AB  - Phylogeographic analyses have revealed the importance of Pleistocene vicariance
      events in shaping the distribution of genetic diversity in freshwater fishes.
      However, few studies have examined the patterning of variation in freshwater
      organisms with differing dispersal syndromes and life histories. The present
      investigation addresses this gap, examining the phylogeography of Sida
      crystallina, a species whose production of diapausing eggs capable of passive
      dispersal was thought to constrain its regional genetic differentiation. By
      contrast, the present analysis has revealed deep allozyme and cytochrome oxidase
      I mitochondrial DNA divergence between populations from North America and Europe.
      Moreover, North American populations are separated into four allopatric
      assemblages, whose distribution suggests their derivation from different
      Pleistocene refugia. These lineages show higher haplotype diversity and deeper
      sequence divergence than those of any fish from temperate North America. Its
      distinctive life history traits have evidently sheltered lineages of Sida from
      extinction, contributing to a remarkably comprehensive and high resolution
      phylogeographic record.

PMID- 11298953
TI  - The root rot fungus Armillaria mellea introduced into South Africa by early Dutch
      settlers.
AB  - Dead and dying oak (Quercus) and numerous other woody ornamental trees and shrubs
      showing signs and symptoms of Armillaria root rot were identified in the Company
      Gardens, Cape Town, South Africa, which were established in the mid-1600s by the
      Dutch East Indies Trading Company. Nineteen isolates from dying trees or from
      mushrooms were collected and analysed to identify and characterize the Armillaria
      sp. responsible for the disease. The AluI digestion of the amplified product of
      the first intergenic spacer region (IGS-1) of the rRNA operon of 19 isolates from
      the Company Gardens was identical to that of some of the European isolates of A.
      mellea s. s. The IGS-1 region and the internal transcribed spacers (ITS) were
      sequenced for some of the Cape Town isolates. Phylogenetic analyses placed the
      Cape Town isolates in the European clade of A. mellea, which is distinct from the
      Asian and North American clades of this species. Identification based on sexual
      compatibility was conducted using A. mellea tester strains in diploid-haploid
      pairings, which showed some compatibility between the Cape Town isolates and
      testers from Europe. Somatic compatibility tests (diploid-diploid pairings) and
      DNA fingerprinting with multilocus, microsatellite probes indicated that the Cape
      Town isolates were genetically identical and may have resulted from vegetative
      (clonal) spread from a single focus in the centre of the original Company Gardens
      (c. 1652). The colonized area is at least 345 m in diameter. Assuming a linear
      spread rate underground of 0.3 m/year to 1.6 m/year, the genet (clone) was
      estimated to be between 108 and 575 years old. These data suggest that A. mellea
      was introduced into Cape Town from Europe, perhaps on potted plants, such as
      grapes or citrus, planted in the Company Gardens more than 300 years ago.

PMID- 11298954
TI  - Testing models of diversification in mice in the Abrothrix olivaceus/xanthorhinus
      complex in Chile and Argentina.
AB  - Samples of the forest-dwelling mouse Abrothrix olivaceus and the steppe-dwelling
      A. xanthorhinus across a transect between 45 and 47 degrees S in southern Chile
      were analysed using the mitochondrial cytochrome b (cyt b) sequence,
      substantially adding to the data presented previously for these taxa from
      Argentina and Chile. The level of variation in the cyt b sequence throughout the
      entire olivaceus/xanthorhinus complex is comparable to that seen within a single
      species in many South American sigmodontine rodents, consistent with a previous
      conclusion that both taxa are sub-species of A. olivaceus. Haplotypes of
      xanthorhinus have not yet achieved reciprocal monophyly relative to those of
      olivaceus. We evaluate competing hypotheses for the morphological divergence of
      xanthorhinus and olivaceus by allopatry in Pleistocene refuges versus postglacial
      diversification across ecological gradients. Two contrasting patterns are
      predicted for plots of the distribution of pairwise genetic differences,
      depending on whether the taxa diverged in allopatric refuges or through selection
      across a gradient. Examples of both modes of diversification are found in this
      complex.

PMID- 11298956
TI  - The use of amplified fragment length polymorphism in determining species trees at
      fine taxonomic levels: analysis of a medically important snake, Trimeresurus
      albolabris.
AB  - There are a huge number of phylogenetic studies based on mitochondrial DNA
      (mtDNA); however, these may represent gene trees that may not be congruent with
      the species tree. A solution to this problem is to include additional,
      independent, loci from the nuclear genome. At fine taxonomic levels, i.e. between
      populations and closely related species, previously suggested nuclear markers
      such as intron sequence data may not be appropriate. In this study we investigate
      the use of amplified fragment length polymorphisms (AFLP) to aid determination of
      the species tree for 24 specimens of a medically important snake, Trimeresurus
      albolabris. This is of particular importance for many venomous snakes as venom
      often varies intraspecifically. Five different primer combinations produced 434
      bands and were analysed by constructing a phylogenetic tree using neighbour
      joining and principal component analysis. Results were similar across all methods
      and found distinct groupings. The results were compared with mtDNA data and a
      reconciled tree was constructed in order to determine the species tree for T.
      albolabris. We found that T. albolabris (sensu lato) is not monophyletic.
      Specimens from the Indonesian islands (except West Java) form a distinct clade
      and we propose elevation to species level. A specimen from Nepal is also distinct
      and suggests that this population also deserves specific status. We suggest that
      AFLPs may prove a valuable aid in determining species trees as opposed to gene
      trees at fine taxonomic levels and this should facilitate the incorporation of
      molecular data into such activities as antivenom production and conservation
      management.

PMID- 11298955
TI  - Population structure and biogeography of migratory freshwater fishes
      (Prochilodus: Characiformes) in major South American rivers.
AB  - Mitochondrial DNA (mtDNA) sequences were used to infer the phylogenetic
      relationships of Prochilodus species in the Parana, Amazonas, Orinoco, and
      Magdalena basins. Sequences of ATPase subunits 6 and 8 (total 840 bp) were
      obtained for 21 Prochilodus specimens from the four river systems. Using
      Semaprochilodus as an outgroup, phylogenetic analyses showed that: (i) each river
      basin contains a monophyletic group of mtDNA lineages; and (ii) the branching
      order places Magdalena in a basal position with subsequent branching of Orinoco,
      Amazon and Parana. The mitochondrial control region was sequenced for 26 P.
      lineatus (from the Parana basin) and six other Prochilodus specimens from the
      Magdalena, Orinoco and Amazon. All 26 control region haplotypes were unique with
      sequence divergence ranging from 0.3 to 3.6%. The control region phylogeny is
      well resolved but phylogenetic structure is not associated with geography. For
      example, mtDNA haplotypes from the upper Parana (Mogui Guassu) and the upper
      Bermejo, separated by at least 2600 km, have close genealogical ties.
      Phylogeographic analyses, including nested clade analysis, suggest high levels of
      gene flow within this basin.

PMID- 11298957
TI  - Mitochondrial DNA, ecology and morphology: interpreting the phylogeography of the
      Nesotes (Coleoptera: Tenebrionidae) of Gran Canaria (Canary Islands).
AB  - The genus Nesotes (Coleoptera: Tenebrionidae) is represented in the Canary
      Islands by 19 endemic species, the majority of which are single island endemics.
      Nesotes conformis and N. fusculus are described on four and three islands,
      respectively, but each forms a paraphyletic assemblage between Gran Canaria and
      the other islands. The other described species for Gran Canaria are N. quadratus,
      N. lindbergi and N. piliger. Thirty-six individuals representing the five species
      on Gran Canaria have been sequenced for 675 bp of the mitochondrial DNA (mtDNA)
      cytochrome oxidase II gene. Neighbour-joining analysis of maximum likelihood
      distances resulted in five distinct mtDNA lineages for N. quadratus, two of which
      also include mitotypes of N. conformis. Each of the other three species is found
      on only one mtDNA lineage. We propose from the molecular data that
      differentiation in a widespread N. quadratus-type ancestor was followed by
      morphological adaptation to coastal, pine and laurel forest habitats.

PMID- 11298959
TI  - Low reproductive success in territorial male Antarctic fur seals (Arctocephalus
      gazella) suggests the existence of alternative mating strategies.
AB  - Microsatellites were used to conduct an analysis of paternity of Antarctic fur
      seals (Arctocephalus gazella) from Bird Island, South Georgia. At most, only 28%
      of pups at our study site could be assigned a father, even though the majority
      (approximately 90%) of candidate males within this colony were sampled. The
      behavioural and genetic evidence from this study suggests that a number of
      alternative mating strategies may exist within this fur seal population. Holding
      a land-based territory conferred an advantage to male reproductive success.
      However, this advantage was much smaller than expected from behavioural
      observations. At least 70% of fur seal pups born at our study site in a given
      year are not fathered by males who held a territory or were observed copulating
      with females in the previous year, implying that there exists a pool of males
      that seldom venture ashore at this site. To explain this discrepancy we suggest
      that female choice is an integral component of the Antarctic fur seal mating
      system and that aquatic mating may play a much larger role in the Antarctic fur
      seal than previously thought.

PMID- 11298958
TI  - A comparison of nuclear and mitochondrial cline shapes in a hybrid zone in the
      Sceloporus grammicus complex (Squamata; Phrynosomatidae).
AB  - The F5 and FM2 chromosome races of the Sceloporus grammicus complex form a hybrid
      zone in the Mexican state of Hidalgo. Previous studies of this zone have assessed
      genetic structure by averaging estimates of shape and width across three
      diagnostic chromosome markers. This approach is likely to mask subtle differences
      in cline shape among loci (e.g. selected vs. neutral), and obscure any
      displacement of cline centres (if present). Here we use maximum likelihood
      methods to construct the best fitting individual clines for three chromosomal
      markers, and also add two new markers; the mitochondrial DNA (mtDNA) locus, and
      the nuclear ribosomal DNA (rDNA) repeat. For each locus, hybrid zone models were
      fitted by cline shape and width, and the position and number of segments
      describing the centre of the zone. Pairwise comparisons between all clines
      revealed concordance between chromosomes 2 and 6, but significant discordance in
      cline structure among all other paired combinations. The concordance of
      chromosomes 2 and 6 suggests that these clines are maintained by genome-wide
      forces. The discordance of the chromosome 1 cline suggests an influence of
      asymmetric introgression, while the mtDNA cline is probably influenced by
      selection and drift. The rDNA locus reveals a pattern best explained by either
      extreme asymmetric introgression or gene conversion. The structure of zone
      indicates that genome-wide processes and locus specific selective forces as well
      as drift, are operating to different degrees on different loci. The locus-by
      locus approach used here permits a finer discrimination among possible mechanisms
      responsible for the maintenance of the individual clines.

PMID- 11298960
TI  - Surprising similarity of sneaking rates and genetic mating patterns in two
      populations of sand goby experiencing disparate sexual selection regimes.
AB  - Molecular markers have proved extremely useful in resolving mating patterns
      within individual populations of a number of species, but little is known about
      how genetic mating systems might vary geographically within a species. Here we
      use microsatellite markers to compare patterns of sneaked fertilization and
      mating success in two populations of sand goby (Pomatoschistus minutus) that
      differ dramatically with respect to nest-site density and the documented nature
      and intensity of sexual selection. At the Tvarminne site in the Baltic Sea, the
      microsatellite genotypes of 17 nest-tending males and mean samples of more than
      50 progeny per nest indicated that approximately 35% of the nests contained eggs
      that had been fertilized by sneaker males. Successful nest holders mated with an
      average of 3.0 females, and the distribution of mate numbers for these males did
      not differ significantly from the Poisson expectation. These genetically deduced
      mating-system parameters in the Tvarminne population are remarkably similar to
      those in sand gobies at a distant site adjoining the North Sea. Thus, pronounced
      differences in the ecological setting and sexual selection regimes in these two
      populations have not translated into evident differences in cuckoldry rates or
      other monitored patterns of male mating success. In this case, the ecological
      setting appears not to be predictive of alternative male mating strategies, a
      finding of relevance to sexual selection theory.

PMID- 11298962
TI  - Spatial structure of lemming populations (Dicrostonyx groenlandicus) fluctuating
      in density.
AB  - The pattern and scale of the genetic structure of populations provides valuable
      information for the understanding of the spatial ecology of populations,
      including the spatial aspects of density fluctuations. In the present paper, the
      genetic structure of periodically fluctuating lemmings (Dicrostonyx
      groenlandicus) in the Canadian Arctic was analysed using mitochondrial DNA
      (mtDNA) control region sequences and four nuclear microsatellite loci. Low
      genetic variability was found in mtDNA, while microsatellite loci were highly
      variable in all localities, including localities on isolated small islands. For
      both genetic markers the genetic differentiation was clear among geographical
      regions but weaker among localities within regions. Such a pattern implies gene
      flow within regions. Based on theoretical calculations and population census data
      from a snap-trapping survey, we argue that the observed genetic variability on
      small islands and the low level of differentiation among these islands cannot be
      explained without invoking long distance dispersal of lemmings over the sea ice.
      Such dispersal is unlikely to occur only during population density peaks.

PMID- 11298961
TI  - Abundance and diversity of Schizophyllum commune spore clouds in the Caribbean
      detected by selective sampling.
AB  - Selective spore trapping and molecular genotyping methods were employed to
      examine potential long-distance gene flow among Caribbean populations of the
      common mushroom Schizophyllum commune. Spore-trap samples from five locations
      were analysed using restriction fragment polymorphisms of five enzymatically
      amplified gene regions. Successful trappings suggested S. commune spores to be
      abundant in the air, with an estimated sedimentation rate of approximately 18
      spores/m2/h. High levels of genetic diversity characterized the spore-trap
      samples, with as many as 12 alleles observed at a single locus (chitin synthase)
      over all samples. In addition, spore-trap samples showed significant among sample
      heterogeneity including geographical population substructure. The ribosomal DNA
      (rDNA) intergenic spacer displayed the greatest allele frequency differences
      among samples, clearly separating the samples into those possessing only a South
      American-type allele and those segregating for both North and South American-type
      alleles. The molecular variation provided no clear evidence for dispersal over
      large, aquatic barriers within the Caribbean region, and instead suggested that
      spore-trapping experiments are primarily reflective of the local, established
      population.

PMID- 11298963
TI  - Genetic variation and clonal diversity in four clonal sedges (Carex) along the
      Arctic coast of Eurasia.
AB  - We studied the structure of genetic variation (at both ramet- and genet-level)
      and clonal diversity within and among populations in the four closely related
      arctic clonal sedges Carex bigelowii, C. ensifolia, C. lugens and C. stans by use
      of allozyme markers. Compared to other sedges and arctic plants, the studied taxa
      all had high levels of genetic variation, both within populations and taxa. These
      taxa contained most of the total gene diversity (H(T)) within populations and a
      small part of the diversity among populations (G(ST) ranged 0.05--0.43). Carex
      bigelowii had genetic variation (H(S) = 0.173, mean for populations) at a
      comparable level to other outbreeding arctic plants and to other widespread,
      rhizomatous and mainly outbreeding Carex species. In contrast, C. ensifolia (H(S)
      = 0.335), C. lugens (H(S) = 0.339) and C. stans (H(S) = 0.294) had within
      population variations that were higher than in most other studied Carex species
      and for arctic plants in general. Genetic variation was not related to any tested
      environmental variable, but it was lower in areas deglaciated only 10,000 years
      BP compared to areas deglaciated 60,000 years BP or not glaciated at all during
      the Weichselian. All the populations were multiclonal, except for two populations
      of C. stans that were monoclonal. In contrast to genetic variation, clonal
      diversity decreased with latitude and did not differ between areas with different
      times of deglaciation. In accordance with previous studies, C. bigelowii and C.
      lugens were found to be outbreeding, while C. ensifolia and C. stans had mixed
      mating systems.

PMID- 11298964
TI  - Genetic polymorphism in Gymnodinium galatheanum chloroplast DNA sequences and
      development of a molecular detection assay.
AB  - Nuclear and chloroplast-encoded small subunit ribosomal DNA sequences were
      obtained from several strains of the toxic dinoflagellate Gymnodinium
      galatheanum. Phylogenetic analyses and comparison of sequences indicate that the
      chloroplast sequences show a higher degree of sequence divergence than the
      nuclear homologue. The chloroplast sequences were chosen as targets for the
      development of a 5'--3' exonuclease assay for detection of the organism. The
      assay has a very high degree of specificity and has been used to screen
      environmental water samples from a fish farm where the presence of this
      dinoflagellate species has previously been associated with fish kills. Various
      hypotheses for the derived nature of the chloroplast sequences are discussed, as
      well as what is known about the toxicity of the species.

PMID- 11298965
TI  - Immunological analysis of phloem sap of Bacillus thuringiensis corn and of the
      nontarget herbivore Rhopalosiphum padi (Homoptera: Aphididae) for the presence of
      Cry1Ab.
AB  - Phloem sap of transgenic Bacillus thuringiensis (Bt) corn expressing a truncated
      form of the B. thuringiensis delta-endotoxin Cry1Ab, sap sucking aphids feeding
      on Bt corn and their honeydew were analysed for presence of Cry1Ab using ELISA.
      Phloem sap of Bt and non-Bt corn was collected using a newly developed technique
      with a microcapillary being directly inserted into the phloem tubes. Using this
      technique, no Cry1Ab was detected in the phloem sap. In contrast, measurable
      concentrations of Cry1Ab in the range of 1 ppb were detected when phloem sap of
      pooled leaf samples was extracted using EDTA buffer. This was probably because of
      Cry1Ab toxin released from damaged cells. When analysing apterous adults of
      Rhopalosiphum padi L. and their honeydew, no Cry1Ab could be detected. In
      contrast, Cry1Ab was clearly detected in both larvae of the leaf chewing
      herbivore Spodoptera littoralis (Boisduval) and their faeces, showing that Cry1Ab
      is detectable after ingestion and excretion by herbivores. These results suggest
      that R. padi ingests or contains no or only very low concentrations of Cry1Ab in
      the range of the detection limit. In consequence it is hypothesized that R. padi
      as an important prey for beneficial insects in corn is unlikely to cause any harm
      to its antagonists due to mediating Bt toxin.

PMID- 11298967
TI  - Speciation, hybrid zones and phylogeography - or seeing genes in space and time.
AB  - The origins and development of the study of speciation, hybrid zones and
      phylogeography are outlined using evolutionary iconography. This traces the ideas
      in this field from Lamarck and Darwin through to the present as represented in
      diagrams and figures. A 'tree of trees' summarizes this growth and current
      vitality. The new facility to use various DNA sequences from nuclear,
      mitochondrial and chloroplast genomes to determine genetic variation throughout a
      species range is examined particularly. There is great genomic subdivision across
      species distributions, which can be interpreted in the light of the recent
      demonstrations of severe palaeoclimatic oscillations. Refugia and postglacial
      colonization routes are proposed for several organisms across Europe. The role of
      geography in speciation through the Pleistocene is considered. These emerging
      principles and analyses are applied to data available on a variety of organisms
      in other regions of the world, such as the Arctic, North America and the Tropics,
      and including the progress of Homo sapiens through the last ice age. Some
      suggestions are made for future research directions.

PMID- 11298968
TI  - The role of hybridization in evolution.
AB  - Hybridization may influence evolution in a variety of ways. If hybrids are less
      fit, the geographical range of ecologically divergent populations may be limited,
      and prezygotic reproductive isolation may be reinforced. If some hybrid genotypes
      are fitter than one or both parents, at least in some environments, then
      hybridization could make a positive contribution. Single alleles that are at an
      advantage in the alternative environment and genetic background will introgress
      readily, although such introgression may be hard to detect. 'Hybrid speciation',
      in which fit combinations of alleles are established, is more problematic; its
      likelihood depends on how divergent populations meet, and on the structure of
      epistasis. These issues are illustrated using Fisher's model of stabilizing
      selection on multiple traits, under which reproductive isolation evolves as a
      side-effect of adaptation in allopatry. This confirms a priori arguments that
      while recombinant hybrids are less fit on average, some gene combinations may be
      fitter than the parents, even in the parental environment. Fisher's model does
      predict heterosis in diploid F1s, asymmetric incompatibility in reciprocal
      backcrosses, and (when dominance is included) Haldane's Rule. However, heterosis
      arises only when traits are additive, whereas the latter two patterns require
      dominance. Moreover, because adaptation is via substitutions of small effect,
      Fisher's model does not generate the strong effects of single chromosome regions
      often observed in species crosses.

PMID- 11298969
TI  - Genetic population structure and introgression in Anopheles dirus mosquitoes in
      South-east Asia.
AB  - Genetic structure and species relationships were studied in three closely related
      mosquito species, Anopheles dirus A, C and D in Thailand using 11 microsatellite
      loci and compared with previous mitochondrial DNA (mtDNA) data on the same
      populations. All three species were well differentiated from each other at the
      microsatellite loci. Given the almost complete absence of mtDNA differentiation
      between An. dirus A and D, this endorses the previous suggestion of mtDNA
      introgression between these species. The high degree of differentiation between
      the northern and southern population of An. dirus C (RST = 0.401), in agreement
      with mtDNA data, is suggestive of incipient species. The lack of genetic
      structure indicated by microsatellites in four populations of An. dirus A across
      northern Thailand also concurs with mtDNA data. However, in An. dirus D a limited
      but significant level of structure was detected by microsatellites over ~400 km
      in northern Thailand, whereas the mtDNA detected no population differentiation
      over a much larger area (>1200 km). There is prior evidence for population
      expansion in the mtDNA. If this is due to a selective sweep originating in An.
      dirus D, the microsatellite data may indicate greater barriers to gene flow
      within An. dirus D than in species A. Alternatively, there may have been
      historical introgression of mtDNA and subsequent demographic expansion which
      occurred first in An. dirus D so enabling it to accumulate some population
      differentiation. In the latter case the lack of migration-drift equilibrium
      precludes the inference of absolute or relative values of gene flow in An. dirus
      A and D.

PMID- 11298970
TI  - Plague dynamics and population genetics of the desert locust: can turnover during
      recession maintain population genetic structure?
AB  - The desert locust (Schistocerca gregaria) undergoes crowding-induced phase
      transformation from solitary form to gregarious form. The transformations
      involves changes in behaviour, colour, development, morphometry, fecundity and
      endocrine physiology. Recession populations of the desert locust exist primarily
      in the solitary phase as small populations in patchy environments and are prone
      to extinction because of climatic events. Significant genetic differentiation
      among recession populations along the Red Sea coast of Eritrea was previously
      reported. It was hypothesized that despite the mixing effect of recurrent swarms,
      metapopulation dynamics could have produced genetic divergence among these highly
      scattered recession populations. A Monte Carlo simulation of the population
      dynamics of the desert locust in a metapopulation setting, with a realistic range
      of parameter values clearly demonstrated that this is possible. Population growth
      was represented by a discrete-time logistic equation. The duration of recessions
      and swarms was sampled from normal distributions whose means and standard
      deviations were varied based on reported estimates. An average recession duration
      of 10 +/- 3 generations and swarm periods half as long but almost twice as
      variable produced a partitioning of the total genetic variance most similar to
      that in the empirical study. In conventional metapopulation analysis, whether
      turnover leads to increased or reduced divergence is dependent on the number of
      colonists relative to the number of recurrent migrants, and on whether the
      colonists arise from a single patch or many patches. In the case of locusts, the
      stochastic boom and bust cycle is the overriding factor. Divergence between
      patches during recession due to founder effect and recurrent drift is balanced by
      the high rate of mixing during plagues.

PMID- 11298971
TI  - Sustaining genetic variation in a small population: evidence from the Mauritius
      kestrel.
AB  - We obtained measures of genetic diversity in 10 kestrel species at a suite of 12
      microsatellite loci. We estimated the relative effective size (Ne) of the species
      using a Markov chain Monte Carlo (MCMC) approach, which jointly estimated the
      locus specific mutation rates as nuisance parameters. There was surprisingly high
      genetic diversity found in museum specimens of the Mauritius kestrel. Being an
      endemic species on a small island, it is known to have a long history of small
      population size. Conversely, kestrels with a continental distribution had Ne
      estimates that were only one order of magnitude larger and similar to each other,
      despite having current population sizes that were between one and three orders of
      magnitude larger than the Mauritius kestrel. We show how many of the theoretical
      results describing the effective size of a subdivided population can be captured
      in terms of three rates which describe the branching pattern of the gene
      genealogy, and that they are useful in estimating the time to migration-drift and
      mutation-drift equilibrium. We use this approach to argue that population
      subdivision has helped retain genetic diversity in the Mauritius kestrel, and
      that the continental species' genetic diversity has yet to reach equilibrium
      after the range changes following the last ice age. We draw parallels with
      Hewitt's observation that genetic variation seems to survive species' range
      compression and is rather vulnerable to range expansion.

PMID- 11298972
TI  - Mitochondrial DNA variation and GIS analysis confirm a secondary origin of
      geographical variation in the bushcricket Ephippiger ephippiger (Orthoptera:
      Tettigonioidea), and resurrect two subspecies.
AB  - Geographic variation within species can originate through selection and drift in
      situ (primary variation) or from vicariant episodes (secondary variation). Most
      patterns of subspecific variation within European flora and fauna are thought to
      have secondary origins, reflecting isolation in refugia during Quaternary ice
      ages. The bushcricket Ephippiger ephippiger has an unusual pattern of
      geographical variability in morphology, behaviour and allozymes in southern
      France, which has been interpreted as reflecting recent primary origins rather
      than historical isolation. Re-analysis of this variation using Geographical
      Information Systems (GIS) suggests a possible zone of hybridization within a
      complex pattern of geographical variation. Here we produce a genetic distance
      matrix from restriction fragment length polymorphism (RFLP) bandsharing of an
      approximately 4.5 kb fragment of mitochondrial DNA (mtDNA), and compare this with
      predictions resulting from the GIS analysis. The mtDNA variation supports a
      postglacial origin of geographical variation. Partial Mantel test comparisons of
      genetic distances with matrices of geographical distance, relevant environmental
      characteristics and possible refugia show refugia to be the best predictors of
      genetic distance. There is no evidence to support isolation by distance. However,
      environmental contrasts do explain significant variation in genetic distance
      after allowing for the effect of refugial origin. Also, a neighbour-joining tree
      has a major division separating eastern and western forms. We conclude that the
      major source of variation within the species is historical isolation in glacial
      refugia, but that dispersal, hybridization and selection associated with
      environmental features has influenced patterns of mtDNA introgression. At least
      two valid subspecies can be defined.

PMID- 11298973
TI  - Raciation and speciation in house mice from the Alps: the role of chromosomes.
AB  - There are at least 24 different karyotypic races of house mouse in the central
      Alps, each characterized by a different complement of ancestral acrocentric and
      derived metacentric chromosomes; altogether 55 different metacentric chromosomes
      have been described from the region. We argue that this chromosome variation
      largely arose in situ. If these races were to make contact, in most cases they
      would produce F1 hybrids with substantial infertility (sometimes complete
      sterility), due to nondisjunction and germ cell death associated with the
      formation of long-chain and/or ring configurations at meiosis. We present
      fertility estimates to confirm this for two particular hybrid types, one of which
      demonstrates male-limited sterility (in accordance with Haldane's Rule). As well
      as a model for speciation in allopatry, the Alpine mouse populations are of
      interest with regards speciation in parapatry: we discuss a possible
      reinforcement event. Raciation of house mice appears to have happened on numerous
      occasions within the central Alps. To investigate one possible source of new
      karyotypic races, we use a two-dimensional stepping stone model to examine the
      generation of recombinant races within chromosomal hybrid zones. Using field
      derived ecological data and laboratory-derived fertility estimates, we show that
      hybrid karyotypic races can be generated at a reasonable frequency in
      simulations. Our model complements others developed for flowering plants that
      also emphasize the potential of chromosomal hybrid zones in generating new stable
      karyotypic forms.

PMID- 11298974
TI  - Spatio-temporal dynamics of the Allonemobius fasciatus- A. socius mosaic hybrid
      zone: a 14-year perspective.
AB  - Long-term studies of hybrid zones can provide valuable insight into a number of
      questions that have long attracted the attention of evolutionists. These
      questions range from the stability and fate of hybrid zones to the relative
      fitness of hybrids. In this paper we report the results of a 14-year survey of
      the Allonemobius fasciatus-Allonemobius socius hybrid zone. Populations were
      collected intensively in 1986 and 1987 and then more sporadically through the end
      of the 1980s and throughout the 1990s. By documenting changes in the genetic
      composition of populations near and within the zone during this period of time we
      assessed: the strength of the reproductive isolation between the two species; the
      relative growth rates (which can be considered a surrogate of relative fitness)
      of genotype classes corresponding to hybrids and to pure species individuals;
      and, the power of single-year and multi-year measurements of relative growth
      rates to predict changes in the genetic composition of mixed populations through
      time. In brief, we found very large year-to-year variation in the relative growth
      rates of pure species and hybrid individuals. This variation may reflect the fact
      that both species are at the edge of their range and perhaps at the limits of
      their ability to deal with environmental perturbations. As a consequence of the
      variation, even multi-year estimates of relative growth rates often provided
      imprecise predictions regarding the future genotypic composition of mixed
      populations. Despite our limited ability to predict the dynamics of individual
      populations, some trends are apparent. A. socius, the southern species, has
      clearly increased in frequency along a transect through the Appalachian
      Mountains, indicating that the zone is moving north in this region. In contrast,
      the zone appeared to be more stable along the East Coast transect. Within mixed
      populations, character-index profiles are often bimodal and stable through time,
      indicating relatively strong reproductive isolation between the two species that
      is not being reinforced, nor is it breaking down.

PMID- 11298975
TI  - Temporal and spatial dynamics of a parapatric boundary between two Australian
      reptile ticks.
AB  - Two tick species Aponomma hydrosauri and Amblyomma limbatum that infest large
      reptiles have an abrupt parapatric boundary near Mt Mary in South Australia. A
      previous model has suggested that the boundary is maintained at population
      density troughs resulting from habitat heterogeneity along a gradual
      environmental gradient. This paper describes the dynamics of the boundary on
      three transects over 17 years, 1982-98. Over the last seven years of that period
      there has been a significant increase in rainfall. At the same time, the boundary
      position has moved 1-2 km on the transects, with the more mesic adapted Ap.
      hydrosauri advancing into the distribution of the more xeric adapted Amb.
      limbatum. Also over the same time the density of ticks on lizards in regions
      flanking the boundary zone has increased for Ap. hydrosauri and decreased for
      Amb. limbatum. These results suggest that the environmental gradient has been
      altered, perhaps by increased rainfall, to favour Ap. hydrosauri, which has been
      able to colonize more successfully across the density troughs and extend its
      distribution.

PMID- 11298976
TI  - Divergence between Drosophila santomea and allopatric or sympatric populations of
      D. yakuba using paralogous amylase genes and migration scenarios along the
      Cameroon volcanic line.
AB  - We have used two paralogous genes (Amyrel and Amy) of the amylase multigene
      family to reconstruct the phylogeny of the nine Drosophila melanogaster subgroup
      sister species, including D. santomea, the newly discovered endemic from Sao Tome
      island. The evolutionary divergence of these genes is of special interest as it
      is suspected to result from physiological evolution via gene duplication. This
      paper describes the relationship between the geographical origin of the various
      strains and the patterns of mating and phylogeny, focusing on the evolution of D.
      santomea and its relationship to other species and their niches. The Amyrel and
      Amy data indicate that, contrary to expectations, the sympatric insular D. yakuba
      population is less closely related to D. santomea than allopatric mainland ones,
      suggesting that the extant insular D. yakuba population on Sao Tome results from
      a recent secondary colonization. Data for sympatric and allopatric D. yakuba
      suggest that D. santomea arose from a mainland D. yakuba parental stock when
      montane habitats of the Cameroon volcanic line extended to lower altitudes during
      colder and less humid periods. Despite their different modes of evolution and
      different functions, the Amyrel and Amy genes provide remarkably consistent
      topologies and hence reflect the same history, that of the species.

PMID- 11298977
TI  - Allochronic speciation, secondary contact, and reproductive character
      displacement in periodical cicadas (Hemiptera: Magicicada spp.): genetic,
      morphological, and behavioural evidence.
AB  - Periodical cicadas have proven useful in testing a variety of ecological and
      evolutionary hypotheses because of their unusual life history, extraordinary
      abundance, and wide geographical range. Periodical cicadas provide the best
      examples of synchronous periodicity and predator satiation in the animal kingdom,
      and are excellent illustrations of habitat partitioning (by the three
      morphologically distinct species groups), incipient species (the year classes or
      broods), and cryptic species (a newly discovered 13-year species, Magicicada
      neotredecim). They are particularly useful for exploring questions regarding
      speciation via temporal isolation, or allochronic speciation. Recently, data were
      presented that provided strong support for an instance of allochronic speciation
      by life-cycle switching. This speciation event resulted in the formation of a new
      13-year species from a 17-year species and led to secondary contact between two
      formerly separated lineages, one represented by the new 13-year cicadas (and
      their 17-year ancestors), and the other represented by the pre-existing 13-year
      cicadas. Allozyme frequency data, mitochondrial DNA (mtDNA), and abdominal colour
      were shown to be correlated genetic markers supporting the life-cycle
      switching/allochronic speciation hypothesis. In addition, a striking pattern of
      reproductive character displacement in male call pitch and female pitch
      preference between the two 13-year species was discovered. In this paper we
      report a strong association between calling song pitch and mtDNA haplotype for
      101 individuals from a single locality within the M. tredecim/M. neotredecim
      contact zone and a strong association between abdomen colour and mtDNA haplotype.
      We conclude by reviewing proposed mechanisms for allochronic speciation and
      reproductive character displacement.

PMID- 11298978
TI  - Intimately linked or hardly speaking? The relationship between genotype and
      environmental gradients in a Louisiana Iris hybrid population.
AB  - Several models of hybrid zone evolution predict the same spatial patterns of
      genotypic distribution whether or not structuring is due to environment-dependent
      or -independent selection. In this study, we tested for evidence of environment
      dependent selection in an Iris fulva x Iris brevicaulis hybrid population by
      examining the distribution of genotypes in relation to environmental gradients.
      We selected 201 Louisiana Iris plants from within a known hybrid population (80 m
      x 80 m) and placed them in four different genotypic classes (I. fulva, I. fulva
      like hybrid, I. brevicaulis-like hybrid and I. brevicaulis) based on seven
      species-specific random amplified polymorphic DNA (RAPD) markers and two
      chloroplast DNA haplotypes. Environmental variables were then measured. These
      variables included percentage cover by tree canopy, elevation from the high water
      mark, soil pH and percentage soil organic matter. Each variable was sampled for
      all 201 plants. Canonical discriminant analysis (CDA) was used to infer the
      environmental factors most strongly associated with the different genotypic
      groups. Slight differences in elevation (-0.5 m to +0.4 m) were important for
      distinguishing habitat distributions described by CDA, even though there were no
      statistical differences between mean elevations alone. I. brevicaulis occurred in
      a broad range of habitats, while I. fulva had a narrower distribution. Of all the
      possible combinations, I. fulva-like hybrids and I. brevicaulis-like hybrids
      occurred in the most distinct habitat types relative to one another. Each hybrid
      class was not significantly different from its closest parent with regard to
      habitat occupied, but was statistically unique from its more distant parental
      species. Within the hybrid genotypes, most, but not all, RAPD loci were
      individually correlated with environmental variables. This study suggests that,
      at a very fine spatial scale, environment-dependent selection contributed to the
      genetic structuring of this hybrid zone.

PMID- 11298979
TI  - The contribution of epistasis to species differences in annual sunflowers.
AB  - The contribution of epistasis to 15 morphological traits differentiating two
      annual sunflowers (Helianthus annuus and H. debilis ssp. cucumerifolius) and to
      hybrid pollen sterility was estimated in a first generation backcross (BC1)
      mapping population. Analysis of digenic interactions among quantitative trait
      loci (QTLs) with significant main effects revealed significant interaction
      effects for six of the 15 morphological traits and for pollen sterility.
      Likewise, a genome-wide scan of all possible two-locus combinations detected
      additional significant interactions for three of the traits with significant
      epistasis in the original analysis: stem pigmentation, phyllary pubescence, and
      pollen viability. However, these were the only traits of the 16 examined in which
      detected interactions explained more than 5% of phenotypic variance. The
      implications of these findings for adaptive evolution and for the introgression
      of advantageous morphological QTLs across a natural hybrid zone between these
      taxa are discussed.

PMID- 11298980
TI  - Did the pleistocene glaciations promote divergence? Tests of explicit refugial
      models in montane grasshopprers.
AB  - There is a long-standing debate over whether or not the Pleistocene glaciations
      promoted speciation. While some models predict that extensive mixing of
      populations during interglacial expansion would have inhibited divergence, others
      postulate that divergence among allopatric glacial refuges or founder events
      during recolonization of previously glaciated areas would have promoted
      differentiation. Using a combination of traditional and coalescent based
      population genetic approaches, this study finds that the glaciations did not
      inhibit divergence among populations of the grasshopper Melanoplus oregonensis.
      Instead, drift associated with recolonization of previously glaciated areas, as
      well as divergence among multiple allopatric glacial refugia, have both
      contributed to differentiation in this montane grasshopper from the 'sky islands'
      of the northern Rocky Mountains. Significant population structure was detected by
      phylogenetic and FST analyses, including significant FST values among individual
      pairs of sky-island populations. In addition to clustering of haplotypes within
      populations, there is some evidence of regional phylogeographic structure,
      although none of the 'regional groups' form a monophyletic clade and there is a
      lack of concordance between the genealogical and geographical positions of some
      haplotypes. However, coalescent simulations confirm there is significant regional
      phylogeographic structure that most likely reflects divergence among multiple
      ancestral refugial populations, and indicate that it is very unlikely that the
      observed gene tree could have been produced by the fragmentation of a single
      widespread ancestral population. Thus, rather than inhibiting differentiation,
      the glaciations appear to have promoted population divergence in M. oregonensis,
      suggesting that they may have contributed to the radiation of Melanoplus species
      during the Pleistocene.

PMID- 11298981
TI  - Do Wolbachia infections play a role in unidirectional incompatibilities in a
      field cricket hybrid zone?
AB  - Two closely related field crickets, Gryllus firmus and G. pennsylvanicus,
      hybridize along an extensive north-south zone in the eastern United States.
      Crosses between G. firmus males and G. pennsylvanicus females produce viable and
      fertile F1, but the reciprocal cross consistently fails to produce offspring.
      Wolbachia, a bacterial parasite of arthropods that causes unidirectional
      incompatibilities in a variety of insect species, has been suggested as the cause
      of the observed incompatibility between G. pennsylvanicus and G. firmus. We
      examine the presence/absence of Wolbachia strains, defined by sequencing the ftsZ
      gene, in four cricket populations from the north-eastern United States. Most G.
      firmus individuals are infected (100% in Guilford, Connecticut; 65% in Seaside
      Park, New Jersey) and > 95% of those infected harbour a single strain of
      Wolbachia. All individuals in G. pennsylvanicus populations (Ithaca, New York;
      Sharon, Connecticut) are infected; the majority of individuals carry a second
      strain of Wolbachia, but a significant fraction carry the same strain found
      commonly in G. firmus. The presence of an apparently identical Wolbachia strain
      in crickets of both species means that some crosses between G. pennsylvanicus
      males and G. firmus females should be compatible. We have no evidence of such
      compatibility. Furthermore, if Wolbachia infections are responsible for the
      observed incompatibility between species, then incompatibilities must also exist
      within G. pennsylvanicus, because this species harbours both Wolbachia strains.
      Although some single pair crosses within G. pennsylvanicus do fail to produce
      offspring, the proportion is lower than expected if Wolbachia were responsible.
      Therefore, Wolbachia is unlikely to be involved in reproductive isolation between
      the two cricket species.

PMID- 11298982
TI  - Phylogeography and conservation of impala and greater kudu.
AB  - The phylogeography of the bush habituated African bovid species impala (Aepyceros
      melampus) and greater kudu (Tragelaphus strepsiceros) is investigated using
      mitochondrial DNA (mtDNA) markers. Combined analysis of individual lineages,
      relationships and population genetics suggest a colonization process from
      Southern Africa toward Eastern regions in the greater kudu. Results are less
      clear for the impala, although remaining consistent with a similar pattern of
      historical dispersion. The study reveals a similar pattern, that is a marked
      divergence of lineages from South-western Africa relative to other regions. This
      pattern is opposed to previously published findings in other African bovid
      species. In the impala, the genetically isolated region is consistent with
      morphology because it is recognized as the subspecies A. m. petersi, the black
      faced impala. In contrast, the similar split of South-western mitochondrial
      lineages was not expected in the greater kudu on the basis of morphology. Both
      species show a significant population genetic differentiation. Beyond their
      phylogeographical value, our results should raise conservation concerns about
      South-western populations of both species. The black-faced impala is categorized
      as vulnerable and our data show indications of hybridization with common impala
      A. m. melampus. The previously unrecognized genetic status of the South-western
      kudus could also imply conservation regulations.

PMID- 11298983
TI  - The effect of habitat type on speciation rates and range movements in aquatic
      beetles: inferences from species-level phylogenies.
AB  - Most aquatic beetles in the family Dytiscidae are tightly associated either with
      running (lotic) or stagnant (lentic) water bodies. The range size of lotic
      species is known to be, on average, much smaller than that of lentic species,
      presumably as a result of differences in dispersal strategies in each habitat
      type. We explored possible effects of these differences on clade evolution and
      speciation rates by comparing species-level phylogenies based on cytochrome
      oxidase I (COI) and 16S rRNA mitochondrial genes for two genera, the lentic
      Ilybius and the lotic Deronectes. The expectation that species turnover is higher
      in lotic lineages due to their lower dispersal propensity compared to lentic
      species was not strongly supported. Deronectes displays a higher frequency of
      recent splits than Ilybius, consistent with the hypothesis, but the difference
      was not significant compared to expected patterns under a constant speciation
      rate null model. Similarly, when the degree of sympatry was plotted against
      relative node age, more allopatric splits were evident in the lentic Deronectes,
      suggesting a slower rate of range movement since speciation, but the differences
      were not significant. We discuss two explanations for our failure to detect
      differences between the two clades. First, current methods for analysing species
      level phylogenies may be sensitive to taxonomic and sampling artefacts. Second,
      lentic and lotic clades may indeed display similar levels of species turnover
      despite occupying very different habitats at different spatial scales. More work
      is needed to investigate the effects of population level processes and spatial
      scale on macroevolutionary dynamics.

PMID- 11298985
TI  - Mating asymmetry and the direction of evolution in the Hawaiian cricket genus
      Laupala.
AB  - Based on studies from native Hawaiian Drosophila, a model was proposed to explain
      sexual isolation and mating asymmetry, from which one could potentially infer the
      'direction of evolution'. We examined sexual isolation between allopatric cricket
      species of the genus Laupala, another endemic Hawaiian insect with an elaborate
      mating system, to begin to explore the nature of sexual isolation and mating
      asymmetry in closely related Hawaiian organisms. We studied sexual isolation and
      mating asymmetry in two contrasts. First, an inter-island comparison, including
      L. makaio from the older island of Maui and L. paranigra from the younger island
      of Hawaii, and second, an intra-island (Hawaii) comparison, including L. nigra
      from the older volcano of Mauna Kea and L. paranigra with a primary distribution
      on the younger volcanoes of Mauna Loa and Kilauea. We used a 'no-choice'
      experimental design, pairing individual males and females in homospecific or
      heterospecific combinations. Several behavioural aspects of courtship (proportion
      of male singing, latency to male singing, production of spermatophores and
      courtship initiation speed) were quantified as well as the success or failure of
      matings. We demonstrate asymmetry in sexual isolation between reciprocal
      combinations of L. makaio and L. paranigra. This result is examined in light of
      the differences in courtship behaviour manifest in the experiments with these two
      species. We did not find evidence of asymmetry in sexual isolation between L.
      nigra and L. paranigra, although differences in courtship initiation speed were
      evident between reciprocal combinations of these two species. In addition to the
      geological argument that species on older islands and older volcanoes give rise
      to species on younger islands and younger volcanoes, we discuss phylogenetic
      evidence consistent with these biogeographic hypotheses of relationships among
      the focal taxa. The patterns of asymmetrical sexual isolation and mating
      asymmetry are consistent with those found in the native Hawaiian Drosophila.

PMID- 11298984
TI  - Speciation, introgressive hybridization and nonlinear rate of molecular evolution
      in flycatchers.
AB  - Evolutionary history of Muscicapidae flycatchers is inferred from nuclear and
      mitochondrial DNA (mtDNA) sequence comparisons and population genetic analysis of
      nuclear and mtDNA markers. Phylogenetic reconstruction based on sequences from
      the two genomes yielded similar trees with respect to the order at which the
      species split off. However, the genetic distances fitted a nonlinear, polynomial
      model reflecting diminishing divergence rate of the mtDNA sequences compared to
      the nuclear DNA sequences. This could be explained by Haldane's rule because
      genetic isolation might evolve more rapidly on the mitochondrial rather than the
      nuclear genome in birds. This is because hybrid sterility of the heterogametic
      sex (females) would predate that of the homogametic sex (males), leading to sex
      biased introgression of nuclear genes. Analyses of present hybrid zones of pied
      (Ficedula hypoleuca) and collared flycatchers (F. albicollis) may indicate a
      slight sexual bias in rate of introgression, but the introgression rates were too
      low to allow proper statistical analyses. It is suggested, however, that the
      observed deviation from linearity can be explained by a more rapid mutational
      saturation of the mtDNA sequences than of the nuclear DNA sequences, as supported
      by analyses of third codon position transversions at two protein coding mtDNA
      genes. A phylogeographic scenario for the black and white flycatcher species is
      suggested based on interpretation of the genetic data obtained. Four species
      appear to have diverged from a common ancestor relatively simultaneously during
      the Pleistocene. After the last glaciation period, pied and collared flycatchers
      expanded their breeding ranges and eventually came into secondary contact in
      Central and Eastern Europe and on the Baltic Isles.

PMID- 11298986
TI  - Differential success in northwards range expansion between ecotypes of the marble
      gallwasp Andricus kollari: a tale of two lifecycles.
AB  - The Marble gallwasp Andricus kollari has a native range divided into two
      geographically separated lifecycles. In Eastern Europe and Turkey, the lifecycle
      involves a sexual generation on Turkey oak, Quercus cerris, while in Iberia and
      North Africa the sexual generation host is cork oak, Q. suber. Over the last 500
      years, A. kollari has expanded its range into northern Europe, following human
      planting of Q. cerris from Italy and the Balkans. We ask: (i) what is the genetic
      relationship between eastern and western distributions of Andricus kollari? Can
      we determine which lifecycle is ancestral, and how long ago they diverged? (ii)
      To what extent have eastern and western native ranges contributed to northwards
      range expansion? (iii) Is there any evidence for hybridization between the two
      life cycle types? We present analyses of allozyme data for 13 polymorphic loci
      and of sequence variation for a 433 bp fragment of the mitochondrial cytochrome b
      gene. These show: (i) that four haplotype lineages (one in Spain, two in
      Hungary/Italy and one in Turkey) diverged more or less simultaneously between 1
      and 2 million years ago, suggesting the existence of at least four refuges
      through recent ice age cycles. Our data cannot resolve which lifecycle type is
      ancestral. (ii) Populations north of putative refuges are divided into two sets.
      Populations in south-west France are allied to Spain, while all remaining
      populations in northern Europe have been colonized from Italy and the Balkans.
      (iii) The transition from one race to another in south-west France is marked by
      abrupt transitions in the frequency of refuge-specific private alleles and
      corresponds closely to the northern limit of the distribution of cork oak.
      Although hybrids were detected in north-west France, none were detected where the
      two lifecycles meet in south-western France. The biology of oak gallwasps
      predicts that any hybrid zone will be narrow, and limited to regions where Q.
      cerris and Q. suber meet. Our data suggest that eastern and western A. kollari
      are effectively separate species.

PMID- 11298987
TI  - Using phylogeographic analyses of gene trees to test species status and
      processes.
AB  - A gene tree is an evolutionary reconstruction of the genealogical history of the
      genetic variation found in a sample of homologous genes or DNA regions that have
      experienced little or no recombination. Gene trees have the potential of
      straddling the interface between intra- and interspecific evolution. It is
      precisely at this interface that the process of speciation occurs, and gene trees
      can therefore be used as a powerful tool to probe this interface. One application
      is to infer species status. The cohesion species is defined as an evolutionary
      lineage or set of lineages with genetic exchangeability and/or ecological
      interchangeability. This species concept can be phrased in terms of null
      hypotheses that can be tested rigorously and objectively by using gene trees.
      First, an overlay of geography upon the gene tree is used to test the null
      hypothesis that the sample is from a single evolutionary lineage. This phase of
      testing can indicate that the sampled organisms are indeed from a single lineage
      and therefore a single cohesion species. In other cases, this null hypothesis is
      not rejected due to a lack of power or inadequate sampling. Alternatively, this
      null hypothesis can be rejected because two or more lineages are in the sample.
      The test can identify lineages even when hybridization and lineage sorting occur.
      Only when this null hypothesis is rejected is there the potential for more than
      one cohesion species. Although all cohesion species are evolutionary lineages,
      not all evolutionary lineages are cohesion species. Therefore, if the first null
      hypothesis is rejected, a second null hypothesis is tested that all lineages are
      genetically exchangeable and/or ecologically interchangeable. This second test is
      accomplished by direct contrasts of previously identified lineages or by
      overlaying reproductive and/or ecological data upon the gene tree and testing for
      significant transitions that are concordant with the previously identified
      lineages. Only when this second null hypothesis is rejected is a lineage elevated
      to the status of cohesion species. By using gene trees in this manner, species
      can be identified with objective, a priori criteria with an inference procedure
      that automatically yields much insight into the process of speciation. When one
      or more of the null hypotheses cannot be rejected, this procedure also provides
      specific guidance for future work that will be needed to judge species status.

PMID- 11298988
TI  - How many species of cichlid fishes are there in African lakes?
AB  - The endemic cichlid fishes of Lakes Malawi, Tanganyika and Victoria are textbook
      examples of explosive speciation and adaptive radiation, and their study promises
      to yield important insights into these processes. Accurate estimates of species
      richness of lineages in these lakes, and elsewhere, will be a necessary
      prerequisite for a thorough comparative analysis of the intrinsic and extrinsic
      factors influencing rates of diversification. This review presents recent
      findings on the discoveries of new species and species flocks and critically
      appraises the relevant evidence on species richness from recent studies of
      polymorphism and assortative mating, generally using behavioural and molecular
      methods. Within the haplochromines, the most species-rich lineage, there are few
      reported cases of postzygotic isolation, and these are generally among allopatric
      taxa that are likely to have diverged a relatively long time in the past.
      However, many taxa, including many which occur sympatrically and do not
      interbreed in nature, produce viable, fertile hybrids. Prezygotic barriers are
      more important, and persist in laboratory conditions in which environmental
      factors have been controlled, indicating the primary importance of direct mate
      preferences. Studies to date indicate that estimates of alpha (within-site)
      diversity appear to be robust. Although within-species colour polymorphisms are
      common, these have been taken into account in previous estimates of species
      richness. However, overall estimates of species richness in Lakes Malawi and
      Victoria are heavily dependent on the assignation of species status to allopatric
      populations differing in male colour. Appropriate methods for testing the
      specific status of allopatric cichlid taxa are reviewed and preliminary results
      presented.

PMID- 11298989
TI  - Prolonged recording of oesophageal and lower oesophageal sphincter pressure using
      a portable water-perfused manometric system.
AB  - The aim of our study was to investigate the recording fidelity of a water
      perfused micromanometric catheter with incorporated sleeve combined with a newly
      developed portable water-perfused manometric system for pharyngeal, oesophageal
      and lower oesophageal sphincter (LOS) pressure recording. The system's
      performance was assessed in prolonged recordings in ambulant gastro-oesophageal
      reflux disease (GORD) patients. Eighty 24-h studies in GORD patients, carried out
      with the perfused portable manometric system, were evaluated. Twelve of these
      recordings were analysed in detail in order to compare oesophageal and LOS motor
      patterns with those described previously. Paired 2-h manometric recordings of the
      pharynx, oesophagus, LOS and stomach, using the new system and a conventional
      perfused stationary manometric system, were performed in eight healthy subjects.
      With the portable manometric system oesophageal contractions, transient LOS
      relaxations, swallow-associated prolonged LOS relaxations and LOS pressures were
      recorded with equal fidelity to the conventional manometric system. Recordings
      obtained with the portable system showed meal-related and diurnal variations in
      oesophageal and LOS variables that were similar to these found in studies using
      conventional equipment. The new manometric system, consisting of a perfused
      micromanometric catheter with incorporated sleeve and a portable perfusion
      system, enables prolonged studies on oesophageal and LOS motor patterns in
      ambulant subjects.

PMID- 11298991
TI  - Reproducibility of antroduodenal motility during prolonged ambulatory recording.
AB  - Ambulatory recording of antroduodenal manometry is a novel technique with several
      advantages over standard stationary manometry recording. Although the feasibility
      of this technique in clinical practice has been demonstrated, reproducibility of
      antroduodenal motility recorded by means of ambulatory manometry has not been
      investigated. To test whether antroduodenal motility recorded by ambulatory
      manometry is reproducible, we performed two 24-h ambulatory antroduodenal
      manometry recordings in 18 healthy subjects according to an identical protocol
      with a 1-week interval. Motility was recorded with a five-channel solid-state
      catheter. Postprandial motility was recorded after consumption of two test meals
      and interdigestive motility was recorded nocturnally. Postprandial antroduodenal
      motor characteristics were identical between the separate recordings. The number
      and duration of nocturnal cycles of the interdigestive migrating motor complex
      were also in the same range. Phase III characteristics in general were not
      different between the two recordings. Only minor alterations were observed in the
      duration of phase III motor fronts with duodenal onset and in the number of
      interdigestive cycles concluded by duodenal onset phase III. Parameters obtained
      by qualitative analysis were comparable between the two recordings. The
      antroduodenal motility pattern, when measured by ambulatory recording with solid
      state catheters under standardized conditions, is very reproducible.

PMID- 11298990
TI  - Haem oxygenase in enteric nervous system of human stomach and jejunum and co
      localization with nitric oxide synthase.
AB  - Recent evidence suggests that carbon monoxide (CO) may be a neurotransmitter,
      similar to nitric oxide (NO) in the enteric nervous system. The distribution of
      haem oxygenase (HO), the biosynthetic enzyme for CO, has been determined in the
      enteric nervous system of animals, but little is known about the distribution of
      HO in human gastrointestinal tract. The present study investigated the expression
      of HO and its colocalization with NO synthase (NOS), the biosynthetic enzyme for
      NO, in human antrum and jejunum. HO isoforms were identified using
      immunohistochemistry and NOS was identified by immunohistochemistry or NADPH-d
      histochemistry. HO-2 immunoreactive (IR) cell bodies in enteric ganglia and nerve
      fibres in longitudinal and circular muscle were found in both antrum and jejunum.
      Co-localization of HO-2 and NOS was about 40% in HO-2 containing cell bodies of
      myenteric ganglia and only 10% or less in cell bodies of submucous ganglia. HO-1
      immunoreactivity was not detected in antrum or jejunum. The results suggest that
      CO is produced in human enteric ganglion neurones and indicate a possible role of
      CO as a neurotransmitter and possible interaction between HO and NOS pathways in
      inhibitory neurotransmission in the human gastrointestinal tract.

PMID- 11298992
TI  - Manometric artefacts suggesting compression of the duodenum by the superior
      mesenteric artery in healthy humans.
AB  - Multi-channel manometry offers the opportunity to study intestinal motor activity
      with high spatiotemporal resolution. We report tonic and phasic intraluminal
      pressure changes in the mid-portion of the horizontal part of the duodenum. In 10
      healthy volunteers, we recorded 2 h of interdigestive duodenal motility using a
      water-perfused catheter. The assembly incorporated 12 duodenal sideholes at 1.5
      cm intervals (D1-D12). Measurement of the antral and duodenal transmucosal
      potential difference (TMPD) was used to maintain a correct position of the
      catheter. The incidence of pressure waves (PWs) increased gradually from proximal
      (D1) to distal (D12) (P < 0.0001), while the mean amplitude of PWs decreased (P <
      0.0001). In eight of 10 subjects, the signals recorded from D9 showed tonic
      pressure elevations with superimposed phasic pressure changes at heart-rate
      frequency, comprising 13.8% of total recording time. In the other two subjects,
      this phenomenon occurred in D8 (9.9% of time). D10 showed a lower incidence of
      PWs compared with neighbouring sideholes (D6-D9/D11-D12) (P < 0.035), with normal
      amplitudes. Fluoroscopy was performed in three subjects and showed that D9 was
      located at the midline. In healthy subjects manometric signals recorded from the
      horizontal part of the duodenum showed localized artefacts, presumably caused by
      compression by the superior mesenteric artery. In addition, a 'silent' region was
      present just distal to this site, the origin of which is uncertain.

PMID- 11298993
TI  - The stomach's response to unappetizing food: cephalic-vagal effects on gastric
      myoelectric activity.
AB  - The aim of this investigation was to determine the effects of sham feeding food
      that was perceived as unappetizing on the cephalic-vagal reflex as measured by
      changes in gastric myoelectric activity. Thirty-eight healthy human participants
      experienced one of two conditions: (i) an appetizing sham feeding condition in
      which participants chewed and expectorated two cooked frankfurters, and (ii) an
      unappetizing sham-feeding condition in which participants chewed and expectorated
      two cold tofu frankfurters. All participants were asked to chew each mouth-full
      of food 6-7 times and to be very careful not to swallow any of the food.
      Electrogastrograms (EGGs) were recorded for 10 min prior to, during, and for 15
      min after sham feeding. A questionnaire was given to each participant after the
      procedure as a manipulation check and to assess food palatability. Results from
      the questionnaire showed, as expected, that the cooked frankfurters were
      significantly more appetizing than the cold tofu frankfurters (P < 0.01). In the
      group sham fed appetizing food, 3 cycles per minute (cpm) power increased during
      sham feeding, but the change was not significant; however, 3 cpm power decreased
      in the group sham fed unappetizing food. This difference was significant (P <
      0.05). In conclusion, we have demonstrated that the cephalic-vagal reflex, as
      measured by power in the 3 cpm frequency region of the EGG, is sensitive to the
      subjective palatability of the food.

PMID- 11298994
TI  - Enhanced intestinal motor response to cholecystokinin in post-Nippostrongylus
      brasiliensis-infected rats: modulation by CCK receptors and the vagus nerve.
AB  - The jejunal inflammation induced in rats by the nematode Nippostrongylus
      brasiliensis is followed by intestinal neuroimmune alterations including mast
      cell hyperplasia and nerve remodelling. On the other hand, cholecystokinin (CCK)
      plays a pivotal role in the regulation of intestinal motility. The aim of this
      study was to determine whether the intestinal motor response to CCK is altered 30
      days after infection by N. brasiliensis. Thus, CCK-8 (50 microg kg(-1)
      intraperitoneally) disrupted the pattern of jejunal migrating myoelectric
      complexes for a longer time in postinfected rats (95.5 +/- 3.5 min) than in
      controls (48.1 +/- 5.1 min). This enhanced jejunal response was also found after
      oral administration of the potent releaser of endogenous CCK, soybean trypsin
      inhibitor. In contrast, no alteration of the inhibition of colonic motility by
      CCK administration was observed. The increased responsiveness of jejunal motility
      to CCK persisted after mast cell stabilisation or depletion but was prevented by
      atropine, devazepide and L-365260 (CCK-A and CCK-B receptor antagonists,
      respectively) and vagotomy. These results indicate that neuroimmune alterations
      after N. brasiliensis infection lead to an increased intestinal motility response
      to CCK that involves a cholinergic mediation, a vagal pathway and alterations in
      intestinal CCK-A and CCK-B receptors.

PMID- 11298995
TI  - Differential gene expression in the small intestines of wildtype and W/W(V) mice.
AB  - Much of the evidence demonstrating the role of interstitial cells of Cajal (ICC)
      in pacemaking and neurotransmission in the gastrointestinal tract comes from
      studies of W/W(V) mice. These animals have few pacemaker ICC in the small bowel
      due to reduced functional Kit protein. We examined gene expression in the small
      intestines of wildtype and W/W(V) mice. RNA expression in the jejunums of
      wildtype and W/W(V) mutants was studied using a differential gene expression
      METHOD: Seven known genes were differentially expressed in wildtype and W/W(V)
      mice. COX7B (cytochrome c oxidase, subunit VIIb) and SORCIN (encoding multidrug
      resistance complex, class 4) were suppressed in both fed and fasted W/W(V) mice.
      Expression of another five genes was increased in W/W(V) mice: ADA (adenosine
      deaminase), MDH1 (malate dehydrogenase), RPL-8 (ribosomal protein L8), SPTB2
      (spectrin, nonerythroid, beta subunit), and p6-5 (encoding phosphorylcholine [PC]
      T-cell suppressor factor [TsF]). Differential expression was the same in fasted
      and fed animals, suggesting that the differences were independent of the dietetic
      state. We conclude that several genes are differentially expressed in the small
      intestines of W/W(V) mice where the major lesion is loss of pacemaker ICC.
      Differential gene display may help develop a molecular profile of motility
      disorders in which ICC are lost.

PMID- 11298996
TI  - Altered electrical activity in colonic smooth muscle cells from dystrophic (mdx)
      mice.
AB  - Because the colon from dystrophic (mdx) mice shows an altered motor pattern,
      probably due to neural disorders, our aim was to examine the electrophysiological
      properties of muscle cells and the functionality of nitrergic transmission in
      circular muscle from normal and mdx colon. Normal colonic cells (resting membrane
      potential [RMP] about -50 mV) showed spontaneous hyperpolarizations (inhibitory
      junction potentials; IJPs) and cyclic slow depolarizations were sometimes
      recorded. Mdx colon had a depolarized RMP (about -36 mV) and spontaneous IJPs,
      but the cyclic activity was never observed. In the normal colon, Nomega-nitro-L
      arginine methyl ester (L-NAME) induced depolarization and abolished the cyclic
      activity. In the mdx colon, L-NAME caused a slight depolarization. Both
      preparations displayed the same value of RMP in the presence of L-NAME. In
      normals, neural stimulation induced nonadrenergic, noncholinergic IJPs composed
      of fast hyperpolarizations followed by a nitrergic slow hyperpolarization,
      selectively abolished by L-NAME. In the mdx colon the evoked IJPs were composed
      only of the initial fast hyperpolarization, the nitrergic component being absent.
      The hyperpolarization to sodium nitroprusside was not significantly different in
      both preparations. We conclude that the colon from animals lacking in dystrophin
      displays different electrophysiological features because of an impairment of
      nitric oxide function.

PMID- 11298997
TI  - The selective vulnerability of nerve cells in Huntington's disease.
AB  - It is now more than 7 years since the genetic mutation causing Huntington's
      disease (HD) was first identified. Unstable CAG expansion in the IT15 gene,
      responsible for disease, is translated into an abnormally long polyglutamine
      (polyQ) tract near the N-terminus of the huntingtin protein. The presence of
      expanded polyQ in the mutant protein leads to its abnormal proteolytic cleavage
      with liberation of toxic N-terminal fragments that tend to aggregate, probably
      first in the cytoplasm. Subsequent nuclear translocation of the cleaved mutant
      huntingtin is associated with formation of intranuclear protein aggregates and
      neurotoxicity, probably involving apoptotic cascades. These processes, which can
      be experimentally modelled in cultured neuronal and non-neuronal cells, seem to
      underlie neurodegeneration in HD, and also other polyQ disorders, such as
      dentatorubro-pallidoluysian degeneration, spinal and bulbar muscular atrophy and
      the spinocerebellar ataxias. They do not, however, explain why within the corpus
      striatum and cerebral cortex certain nerve cells are susceptible to disease and
      others are not. In the human HD brain, vulnerable pyramidal neurones within the
      deeper layers of the cerebral cortex frequently contain large intranuclear
      inclusions composed of N-terminal fragments of huntingtin. Such inclusions are,
      however, rare within neurones of the striatum, even in the medium spiny neurones
      preferentially lost from this region. While inclusions per se do not seem to be
      neurotoxic, they may provide a surrogate marker of molecular pathology. Recent
      studies indicate that the nuclear accumulation of mutant huntingtin interferes
      with transcriptional events. Of particular importance may be the effect on the
      genes encoding neurotransmitter receptor proteins, especially those involved with
      glutamatergic neurotransmission. Such changes may trigger or facilitate a low
      grade, chronic excitotoxicity of the glutamatergic cortical projection neurones
      on their target cells in the striatum, already partly compromised by the toxic
      effects of the HD mutation. This combination of insults, for anatomical reasons
      experienced predominantly by striatal projection neurones, would eventually cause
      their selective demise.

PMID- 11298998
TI  - Cell migration and cerebral cortical development.
AB  - This annotation describes the clinical and pathological features of several
      conditions believed to result from a primary defect in cell migration which
      include the lissencephalies, pachygria, polymicrogyrias, and focal cortical
      dysplasia. A variety of factors must be considered in pathogeneses, including
      cellular proliferation, cell death, post-migrational intracortical growth and
      development, axonogenesis and dendritogenesis. At least two distinct types of
      lissencephaly exist. Classic (also known as Type I) lissencephaly is the
      prototypic pattern being seen in autosomal dominant Miller-Dieker syndrome, in
      addition to autosomal recessive and X-linked forms. The Miller-Dieker syndrome
      locus (LIS-1) encodes the platelet activating factor acetylhydrolase-1, beta1
      subunit. The gene for an X-linked form of lissencephaly (XLIS) encodes a protein
      called doublecortin. Cobblestone (type II) lissencephaly is most commonly seen in
      patients with the Walker-Warburg syndrome, and also occurs in a group of
      disorders associated with congenital muscular dystrophy, including Finnish
      'muscle-eye-brain' disease and Fukuyama muscular dystrophy. Controversy exits as
      to whether polymicrogyria is a malformation or a disruption of development. The
      answer is likely both. Polymicrogyria is believed to arise from defects occurring
      between 17 and 25 or 26 weeks gestation. Heterotopia can be sporadic, inherited
      as a simple Mendelian trait, or may be part of a more complex syndrome being
      characterized by collections of disorganized grey matter in inappropriate places.
      X-linked periventricular heterotopia syndrome is caused by mutations in filamin
      1. In addition to those described above, many other syndromes show lissencephaly,
      pachygyria and polymicrogyria and many cases are not easily classified into any
      particular syndrome.

PMID- 11299000
TI  - Evaluation of the effects of swainsonine, captopril, tangeretin and nobiletin on
      the biological behaviour of brain tumour cells in vitro.
AB  - Although intrinsic tumours of the brain seldom metastasize to distant sites,
      their diffuse, infiltrative-invasive growth within the brain generally precludes
      successful surgical and adjuvant therapy. Hence, attention has now focused on
      novel therapeutic approaches to combat brain tumours that include the use of anti
      invasive and anti-proliferative agents. The effect of four anti-invasive agents,
      swainsonine (a locoweed alkaloid), captopril (an anti-hypertensive drug),
      tangeretin and nobiletin (both citrus flavonoids), were investigated on various
      parameters of brain tumour invasion such as matrix metalloproteinase (MMP)
      secretion, migration, invasion and adhesion. A standard cytotoxicity assay was
      used to optimize working concentrations of the drugs on seven human brain tumour
      derived cell lines of various histological type and grade of malignancy. A
      qualitative assessment by gelatin zymography revealed that the effect of these
      agents varied between the seven cell lines such that the low grade pilocytic
      astrocytoma was unaffected by three of the agents. In contrast, downregulation of
      the two gelatinases, MMP-2 and MMP-9 was seen in the grade 3 astrocytoma
      irrespective of which agent was used. Generally, swainsonine was the least
      effective whereas the citrus flavonoids, particularly nobiletin, showed the
      greatest downregulation of secretion of the MMPs. Furthermore, captopril and
      nobiletin were most efficient at inhibiting invasion, migration and adhesion in
      four representative cell lines (an ependymoma, a grade II oligoastrocytoma, an
      anaplastic astrocytoma and a glioblastoma multiforme). Yet again, the effects of
      the four agents varied between the four cell lines. Nobiletin was, nevertheless,
      the most effective agent used in these assays. In conclusion, the differential
      effects seen on the various parameters studied by these putative anti-invasive
      agents may be the result of interference with MMPs and other mechanisms
      underlying the invasive phenotype. From these pilot studies, it is possible that
      these agents, especially the citrus flavonoids, could be of future therapeutic
      value. However, further work is needed to validate this in a larger study.

PMID- 11299001
TI  - Elevated p53 expression in benign meningiomas protects against recurrence and may
      be indicative of senescence.
AB  - Prediction of recurrence after resection of benign meningiomas represents a
      significant clinical problem. A prospective study commenced in 1984 aimed to
      elucidate the molecular mechanisms involved in the development of abnormal
      karyotype and tumour recurrence in meningiomas. Expression of key cell cycle
      regulators p53, p21, mdm2 and proliferating cell nuclear antigen (PCNA) were
      studied by immunohistochemistry in 85 tumours for which follow-up data was
      available. It was found that most tumours expressed p53, p21 and PCNA, with
      significant correlations between expression of p53 and both p21 and PCNA. As PCNA
      fulfils a multifunctional role its expression may be an unreliable indicator of
      proliferation in benign tumours. The degree of tumour excision remains the best
      prognostic indicator while p53 is the main predictor of abnormal karyotype.
      Karyotype is not however, related to prognosis. Incompletely excised tumours
      which expressed high levels of p53 and p21 did not recur. It is suggested that
      this is indicative of a fully functional p53-mediated DNA damage response
      mechanism. Rather than contributing to tumour progression, p53 is fulfilling its
      role as guardian of the genome in benign meningiomas. This study shows that
      induction of senescence may be an important tumour suppressor mechanism in benign
      tumours.

PMID- 11299002
TI  - Episodic demyelination and subsequent remyelination within the murine central
      nervous system: changes in axonal calibre.
AB  - Exposure of young adult C57BL/6 mice to cuprizone in the diet initiated profound
      and synchronous demyelination of the corpus callosum, which was virtually
      complete by 4 weeks of exposure. Interestingly, even in the face of a continued
      exposure to cuprizone, there was spontaneous remyelination 2 weeks later. This
      remyelination preferentially involved smaller calibre axons. There was a
      suggestion of yet another cycle of demyelination (at 10 weeks) and remyelination
      (at 12 weeks), but by 16 weeks of exposure, the regenerative capacity was
      exhausted and the animals were near death. The relapsing-remitting pattern
      suggests this may be a useful model for certain human demyelinating disorders. In
      contrast to the above chronic model, the corpus callosum from mice exposed to
      cuprizone for only 6 weeks continued to remyelinate, with 67% of the axons being
      myelinated or remyelinated at 10 weeks. Interestingly, a significant reduction in
      the mean value for axonal diameter was observed during acute demyelination. Upon
      remyelination, however, the axonal calibre distribution returned to near-normal.
      In contrast, when mice were maintained on a cuprizone diet for 16 weeks, the mean
      value for axonal diameter was reduced to 60% of normal. These results provide
      further evidence that the interactions between oligodendrocytes and axons alter
      axonal calibre.

PMID- 11299003
TI  - Depletion of endogenous oligodendrocyte progenitors rather than increased
      availability of survival factors is a likely explanation for enhanced survival of
      transplanted oligodendrocyte progenitors in X-irradiated compared to normal CNS.
AB  - Oligodendrocyte progenitors (OPs) survive and migrate following transplantation
      into adult rat central nervous system (CNS) exposed to high levels of X
      irradiation but fail to do so if they are transplanted into normal adult rat CNS.
      In the context of developing OP transplantation as a potential therapy for
      repairing demyelinating diseases it is clearly of some importance to understand
      what changes have occurred in X-irradiated CNS that permit OP survival. This
      study addressed two alternative hypotheses. Firstly, X-irradiation causes an
      increase in the availability of OP survival factors, allowing the CNS to support
      a greater number of progenitors. Secondly, X-irradiation depletes the endogenous
      OP population thereby providing vacant niches that can be occupied by
      transplanted OPs. In situ hybridization was used to examine whether X-irradiation
      causes an increase in mRNA expression of five known OP survival factors, CNTF,
      IGF-I, PDGF-A, NT-3 and GGF-2. The levels of expression of these factors at 4 and
      10 days following exposure of the adult rat spinal cord to X-irradiation remain
      the same as the expression levels in normal tissue. Using intravenous injection
      of horseradish peroxidase, no evidence was found of X-irradiation-induced change
      in blood-brain barrier permeability that might have exposed X-irradiated tissue
      to serum-derived survival factors. However, in support of the second hypothesis,
      a profound X-irradiation-induced decrease in the number of OPs was noted. These
      data suggest that the increased survival of transplanted OPs in X-irradiated CNS
      is not a result of the increases in the availability of the OP survival factors
      examined in this study but rather the depletion of endogenous OPs creating
      'space' for transplanted OPs to integrate into the host tissue.

PMID- 11299004
TI  - The mitochondrial toxin 3-nitropropionic acid induces differential expression
      patterns of apoptosis-related markers in rat striatum.
AB  - The mitochondrial toxin 3-nitropropionic acid (3-NP) causes selective striatal
      lesions in rats and serves as an experimental model for the neurodegenerative
      disorder Huntington's disease (HD). Apoptotic cell death has been implicated for
      the neuronal degeneration that occurs in HD brains. The present study was
      designed to investigate whether the 3-NP-induced cell death in rats involves
      apoptosis and an altered expression of Bcl-2 family proteins. Systemic
      administration of 3-NP via subcutaneous Alzet pumps resulted in lesions of
      variable severity with neuronal loss and gliosis in the striatum. Using the
      terminal transferase-mediated biotinylated-UTP nick end-labelling (TUNEL) of DNA,
      TUNEL-positive cells exhibiting typical apoptotic morphology were detected only
      in the striatum of rats with a severe lesion. Furthermore, the neuronal
      expression of the pro-apoptotic protein Bax was strongly increased in the core of
      the severe lesion. Expression of the anti-apoptotic marker Bcl-2 was unchanged in
      this location, but was enhanced in the margins of the lesions. A moderately
      increased expression of both Bax and Bcl-2 was observed in dark neurones in the
      mild lesion and in the subtle lesion. The presence of nuclear DNA fragmentation,
      strong granular Bax expression and an increased Bax/Bcl-2 ratio in the centre of
      severe lesions suggests the occurrence of apoptotic cell death following 3-NP
      administration. In contrast, the dark compromised neurones observed in 3-NP
      treated animals revealed an equally enhanced expression of both Bax and Bcl-2,
      but lacked TUNEL-labelling, and are therefore not apoptotic.

PMID- 11299006
TI  - Plant acquisition of organic nitrogen in boreal forests.
AB  - Research on plant nitrogen (N) uptake and metabolism has more or less exclusively
      concerned inorganic N, particularly nitrate. Nevertheless, recent as well as
      older studies indicate that plants may have access to organic N sources.
      Laboratory studies have shown that ectomycorrhizal and ericoid mycorrhizal plants
      can degrade polymeric N and absorb the resulting products. Recent studies have
      also shown that some non-mycorrhizal plants are able to absorb amino acids.
      Moreover, amino acid transporters have been shown to be present in both plant
      roots and in mycorrhizal hyphae. Although both mycorrhizal and non-mycorrhizal
      plants appear to have a capacity for absorbing a range of organic N compounds, is
      this capacity realized in the field? Several lines of evidence show that plants
      are outcompeted by microorganisms for organic N sources. Such studies, however,
      have not addressed the issue of spatial and temporal separation between plants
      and microorganisms. Moreover, competition studies have not been able to separate
      uptake by symbiotic and non-symbiotic microorganisms. Qualitative assessment of
      organic N uptake by plants has been performed with dual-labelled glycine in
      several studies. These studies arrive at different conclusions: some indicate
      that plants do not absorb this organic N source when competing with other
      organisms in soil, while others conclude that significant fractions of amino acid
      N are absorbed as intact amino acid. These variable results may reflect species
      differences in the ability to absorb glycine as well as differences in
      experimental conditions and analytical techniques. Although theoretical
      calculations indicate that organic N might add significant amounts of N to plant
      N uptake, direct quantitative assessment of the fraction of plant N derived from
      uptake by organic N sources is a challenge for future research.

PMID- 11299005
TI  - Trypanosoma brucei brucei crosses the blood-brain barrier while tight junction
      proteins are preserved in a rat chronic disease model.
AB  - African trypanosomiasis, sleeping sickness in humans, is caused by the systemic
      infection of the host by the extracellular parasite, the African trypanosome. The
      pathogenetic mechanisms of the severe symptoms of central nervous system
      involvement are still not well understood. The present study examined the routes
      of haematogenous spread of Trypanosoma brucei brucei (Tbb) to the brain, in
      particular on the question whether parasites can cross the blood-brain barrier,
      as well as their effect on tight junction proteins. Rats were infected with Tbb
      and at various times post-infection, the location of the parasite in the central
      nervous system was examined in relation to the brain vascular endothelium,
      visualized with an anti-glucose transporter-1 antibody. The tight junction
      specific proteins occludin and zonula occludens 1, and the possible activation of
      the endothelial cell adhesion molecules ICAM-1 and VCAM-1 were also studied. At
      12 and 22 days post-infection, the large majority of parasites were confined
      within blood vessels. At this stage, however, some parasites were also clearly
      observed in the brain parenchyma. This was accompanied by an upregulation of ICAM
      1/VCAM-1. At later stages, 42, 45 and 55 days post-infection, parasites could
      still be detected within or in association with blood vessels. In addition, the
      parasite was now frequently found in the brain parenchyma and the extravasation
      of parasites was more prominent in the white matter than the cerebral cortex. A
      marked penetration of parasites was seen in the septal nuclei. In spite of this,
      occludin and zonula occludens 1 staining of the vessels was preserved. The
      results indicate that the Tbb parasite is able to cross the blood-brain barrier
      in vivo, without a generalized loss of tight junction proteins.

PMID- 11299007
TI  - The role of photorespiration in redox and energy balance of photosynthetic plant
      cells: A study with a barley mutant deficient in glycine decarboxylase.
AB  - Protoplasts and mitochondria were isolated from leaves of homozygous barley
      (Hordeum vulgare L.) mutant deficient in glycine decarboxylase complex (GDC, EC
      2.1.2.10) and wild-type plants. The photosynthetic rates of isolated protoplasts
      from the mutant and wild-type plants under saturating CO2 were similar, but the
      respiratory rate of the mutant was two-fold higher. Respiration in the mutant
      plants was much more strongly inhibited by antimycin A than in wild-type plants
      and a low level of the alternative oxidase protein was found in mitochondria. The
      activities of NADP- and NAD-dependent malate dehydrogenases were also increased
      in mutant plants, suggesting an activation of the malate-oxaloacetate exchange
      for redox transfer between organelles. Mutant plants had elevated activities of
      NADH- and NADPH-dependent glyoxylate/hydroxypyruvate reductases, which may be
      involved in oxidizing excess NAD(P)H and the scavenging of glyoxylate. We
      estimated distribution of pools of adenylates, NAD(H) and NADP(H) between
      chloroplasts, cytosol and mitochondria. Under photorespiratory conditions,
      ATP/ADP and NADPH/NADP ratios in the mutant were higher in chloroplasts as
      compared to wild-type plants. The cytosolic NADH/NAD ratio was increased, whereas
      the ratio in mitochondria decreased. It is concluded that photorespiration serves
      as an effective redox transfer mechanism from the chloroplast. Plants with a
      lowered GDC content are deficient in this mechanism, which leads to over
      reduction and over-energization of the chloroplasts.

PMID- 11299008
TI  - Effect of ripening on texture, microstructure and cell wall polysaccharide
      composition of olive fruit (Olea europaea).
AB  - Olive fruits at the green, cherry and black stages were used to investigate the
      structural and microstructural changes in tissues during ripening. Scanning
      electron microscopy (SEM) tissue fracture of green olives resulted in cell wall
      breakage of epicarp and mesocarp cells. Tissue fracture resulted in fewer broken
      cells in cherry than in green olives and even less in black olive tissues. Cell
      separation occurred in the middle lamella region in some of the cells of the
      cherry fruit and in most of the black olive cells. Solubilization and loss of
      pectic polysaccharides, mainly the arabinan moiety, and glucuronoxylans occurred
      in the green to cherry stages. The pulp cell wall constituent polysaccharides,
      pectic polysaccharides, cellulose, glucuronoxylans and xyloglucans, were degraded
      and/or solubilized at the cherry to black ripening stages. The resultant
      depolymerization of the pectic polymers, especially those of the middle lamella
      region, was consistent with the progressive cell separation at the different
      ripening stages by SEM. This showed that partial solubilization of pectic,
      hemicellulosic and cellulosic polysaccharides within the cell wall matrix
      weakened the cell wall structures, preventing the breaking of cells when the
      tissues were fractured.

PMID- 11299009
TI  - Involvement of matrix NADP turnover in the oxidation of NAD-linked substrates by
      pea leaf mitochondria.
AB  - The involvement of the internal rotenone-insensitive NADPH dehydrogenase on the
      inner surface of the inner mitochondrial membrane [NDin(NADPH)] in the oxidation
      of strictly NAD+-linked substrates by pea (Pisum sativum L.) leaf mitochondria
      was measured. As estimated by the inhibition caused by 5 uM diphenyleneiodonium
      (DPI) in the presence of rotenone to inhibit complex I, the activity of
      NDin(NADPH) during glycine oxidation (measured both as O2 uptake and as CO2
      release) was 40-50 nmol mg-1 protein min-1. No significant activity of
      NDin(NADPH) could be detected during the oxidation of 2-oxoglutarate, another
      strictly NAD+-linked substrate; this was possibly due to its relatively low
      oxidation rate. Control experiments showed that, even at 125 uM, DPI had no
      effect on the activity of glycine decarboxylase complex (GDC) and lipoamide
      dehydrogenase. The relative activity of complex I, NDin(NADPH), and NDin(NADH)
      during glycine oxidation, estimated using rotenone and DPI, differed depending on
      the pyridine nucleotide supply in the mitochondrial matrix. This was shown by
      loading the mitochondria with NAD+ and NADP+, both of which were taken up by the
      organelle. We conclude that the involvement of NADP turnover during glycine
      oxidation is not due to the direct production of NADPH by GDC but is an indirect
      result of this process. It probably occurs via the interconversion of NADH to
      NADPH by the two non-energy-linked transhydrogenase activities recently
      identified in plant mitochondria.

PMID- 11299010
TI  - Is the infiltration-centrifugation technique appropriate for the isolation of
      apoplastic fluid? A critical evaluation with different plant species.
AB  - The suitability of the infiltration-centrifugation method for collection of
      apoplastic fluid from intact leaves was evaluated for different plant species.
      Large differences with respect to infiltrability of the leaves, which correlated
      inversely with stomatal and mesophyll resistance, became apparent. Osmolality of
      infiltration medium (deionised water, 0.2 mM CaCl2, 10 mM KCl, 180 mM 2-[N
      morpholino]ethane-sulphonic acid) and incubation time, time passed between onset
      of infiltration and end of centrifugation, revealed relatively little influence
      on the composition of the apoplastic washing fluid (AWF). In contrast, the pH of
      the infiltrated solution highly influenced the concentration of sucrose and
      hexoses. With increasing centrifugation force, hexosephosphate isomerase (HPI)
      activity in the AWF, which was taken as an indication for cytoplasmic
      contamination, increased. At the same time, Ca2+ concentration in the AWF
      increased even more. Since Ca2+ cannot originate from the cytoplasm, the
      suitability of HPI as marker for cytoplasmic contamination is questioned. From
      the composition of the AWF, it is concluded that, if centrifugation force does
      not exceed 1 000 g, cytoplasmic contamination is negligible and that the
      infiltration-centrifugation technique reveals an easy and inexpensive way to
      study apoplastic solutes. The infiltration-centrifugation method was also
      suitable to determine apoplastic air volume (Vair) and apoplastic water volume
      (Vwater), which are necessary for the calculation of the ion concentration in the
      leaf apoplast. It could be shown that the leaves of different species and the
      apical and basal leaves of single plants differ in Vair and Vwater.

PMID- 11299011
TI  - Subcellular localization of beta-glucosidase in rye, maize and wheat seedlings.
AB  - The subcellular compartmentation of beta-glucosidase was studied in rye, maize
      and wheat seedlings by immunocytochemical methods. For detection, we used a 10 nm
      gold-labeled secondary antibody, and results were observed using transmission
      electron microscopy. In all three species, beta-glucosidase was found in
      plastids, cytoplasm and cell walls. In rye, gold particles were seen on cell
      walls and cytoplasm in epidermal cells of the root tip and shoot, in bundle
      sheath cells of the shoot and in all cells, except the vascular bundle cells of
      the coleoptile. Gold labeling was also observed in plastids of the bundle sheath
      cells of rye shoot tips and in cortical cells of root tips. In wheat, gold
      labeling was observed on cell walls and cytoplasm of epidermal cells in the shoot
      base and coleoptile, and on cell walls and plastids in epidermal cells of the
      root tip. In maize, gold labeling was mainly found in plastids or proplastids in
      vascular bundle cells and bundle sheath cells of the shoot, in bundle sheath
      cells of the coleoptile and in epidermal cells of the root. Some gold particles
      were also found in cell walls and cytoplasm of stomatal guard cells of the shoot
      base and vascular bundle cells of the shoot tip and in the cell walls of bundle
      sheath cells of the shoot tip and root tip epidermal cells. Results are discussed
      in relation to the role of beta-glucosidase in hydroxamic acid release and
      overall defense mechanism of monocotyledons.

PMID- 11299012
TI  - Osmoconditioning reduces physiological and biochemical damage induced by chilling
      in soybean seeds.
AB  - The aim of the present work was to investigate the effects of osmoconditioning on
      chilling injury in soybean (Glycine max (L.) Merr.) seeds during imbibition.
      Soybean seeds germinated readily over a large range of temperatures (10-35
      degrees C), the thermal optimum being 25-30 degrees C. Low temperatures reduced
      the germination rate and no seed germinated at 1 degrees C. Pre-treatment of
      seeds at 1 degrees C reduced further germination at the optimal temperature (25
      degrees C). This deleterious effect of chilling increased with duration of the
      treatment, and was maximal after 4 days. Osmoconditioning of seeds at 20 degrees
      C with a polyethylene glycol-8000 solution at -1.5 MPa for at least 24 h followed
      by drying back the seeds to their initial moisture content reduced their chilling
      sensitivity and even allowed germination at 1 degrees C. Chilling of control
      seeds resulted in a sharp decline in in vivo ACC-dependent ethylene production
      and in an increase in electrolyte leakage in the medium, which indicated
      deterioration of membrane properties. Osmoconditioned seeds placed at 1 degrees C
      did not show any reduction in their ability to convert ACC to ethylene nor any
      strong increase in electrolyte leakage. Imbibition of both control and
      osmoconditioned seeds at 1 degrees C resulted in a marked increase in ATP level
      (more than 50% of the total nucleotides) and energy charge; however, the latter
      cannot be considered as an indicator of chilling since it remained high (0.74
      0.88) throughout the cold treatment. Chilling treatment longer than 6 days
      induced accumulation of malondialdehyde in the embryonic axis, which was more
      marked in control seeds than in osmoconditioned seeds, suggesting that chilling
      sensitivity was associated with lipid peroxidation. Imbibition of seeds at 1
      degrees C resulted in an increase in superoxide dismutase, catalase and
      glutathione reductase activity, which was generally higher in osmoconditioned
      seeds than in control ones. This stimulation of the antioxidant defence systems
      occurred during the 4 first days of chilling and decreased then in control seeds
      while it remained high in osmoconditioned ones. Re-warming seeds at 25 degrees C
      resulted in an increase in all enzyme activity involved in antioxidant defence.
      However this effect of re-warming decreased in control seeds after 4 days of
      chilling, whereas it was maintained in osmoconditioned seeds.

PMID- 11299013
TI  - Plasma membrane H-ATPase activity is involved in adaptation of tomato calli to
      NaCl.
AB  - A tomato (Lycopersicon esculentum Mill. cv. Pera) callus culture tolerant to NaCl
      was obtained by successive subcultures of NaCl-sensitive calli in medium
      supplemented with 50 mM NaCl. NaCl-tolerant calli grew better than NaCl-sensitive
      calli in media supplemented with 50 and 100 mM NaCl. Analysis of callus ion
      content showed a strong increase in Na+ and Cl- both in NaCl-tolerant and 
      sensitive calli grown in media containing NaCl for one subculture. Cells from
      NaCl-tolerant calli showed a higher H+ extrusion activity than those from NaCl
      sensitive calli grown for one subculture in the presence of NaCl. The inhibition
      of H+ extrusion by NaCl-sensitive cells was correlated with an inhibition of
      microsomal vanadate-sensitive H+-ATPase (EC 3.6.1.35) and ATP-dependent H+
      transport, while the stimulation of H+ extrusion by cells tolerant to 50 mM NaCl
      was correlated with an increase in plasma membrane ATP-dependent H+ transport.
      The increase of ATP-dependent H+ extrusion in plasma membranes isolated from 50
      mM NaCl-tolerant calli was not a result of stimulation of a vanadate-sensitive
      ATP hydrolytic activity or an increase in passive permeability to H+. Relative to
      NaCl-sensitive calli, plasma membrane H+-ATPase from calli tolerant to 50 mM NaCl
      showed a lower Km for Mg2+-ATP. Our results indicate that tolerance of tomato
      calli to 50 mM NaCl increases the affinity of plasma membrane H+-ATPase for the
      substrate ATP and stimulates the H+-pumping activity of this enzyme without
      modifying its phosphohydrolytic activity.

PMID- 11299014
TI  - Seasonal fluctuations in the concentration of UV-absorbing compounds in the
      leaves of some Mediterranean plants under field conditions.
AB  - Leaves of 14 representative Mediterranean plant species were collected on a
      monthly basis and assayed for UV-absorbing compounds concentration, either on an
      area or a dry mass basis, from 1995 to 1997. Strong seasonal fluctuations were
      observed in eight species (all evergreens, two phrygana, one deciduous, one
      summer perennial and one winter perennial). Two different patterns of changing
      concentrations of UV-absorbing compounds were observed. In the first,
      concentration of these compounds was higher in young developing leaves and
      concentration declined during maturation, whereas in other plants, the opposite
      trend was observed. These differences could be attributed to the particular leaf
      surface morphology of each plant. The observed seasonal fluctuations of UV
      absorbing compounds seem to be more correlated to developmental processes, than
      to seasonal fluctuations of the naturally occurring UV-B radiation. Most of the
      winter perennials did not show strong fluctuations during the period of
      development. The concentration of these compounds varied not only on a seasonal
      basis among the examined plants, but between different life forms as well: during
      winter, examination of the leaves of 13 species showed that evergreen
      sclerophylls and phrygana had at least two-fold higher concentration of UV-B
      absorbing compounds on a leaf area basis than winter perennials. In addition,
      during the same season and irrespective of life form and species, the absorbance
      at 300 nm per unit of mature leaf area followed an asymptotic exponential
      decrease when specific leaf area increased. The UV-B radiation screening capacity
      of the leaves of these plants is discussed in relation to each adaptive strategy.

PMID- 11299015
TI  - Does elevated CO2 ameliorate the impact of O3 on chlorophyll content and
      photosynthesis in potato (Solanum tuberosum)?
AB  - This study examined the impact of season-long exposure to elevated carbon dioxide
      (CO2) and ozone (O3), individually and in combination, on leaf chlorophyll
      content and gas exchange characteristics in potato (Solanum tuberosum L. cv.
      Bintje). Plants grown in open-top chambers were exposed to three CO2 (ambient,
      550 and 680 umol mol-1) and two O3 treatments (ambient and elevated; 25 and 65
      nmol mol-1, 8 h day-1 means, respectively) between crop emergence and maturity;
      plants were also grown in unchambered field plots. Non-destructive measurements
      of chlorophyll content and visible foliar injury were made for all treatments at
      2-week intervals between 43 and 95 days after emergence. Gas exchange
      measurements were made for all except the intermediate 550 umol mol-1 CO2
      treatment. Season-long exposure to elevated O3 under ambient CO2 reduced
      chlorophyll content and induced extensive visible foliar damage, but had little
      effect on net assimilation rate or stomatal conductance. Elevated CO2 had no
      significant effect on chlorophyll content, but greatly reduced the damaging
      impact of O3 on chlorophyll content and visible foliar damage. Light-saturated
      assimilation rates for leaves grown under elevated CO2 were consistently lower
      when measured under either elevated or ambient CO2 than in equivalent leaves
      grown under ambient CO2. Analysis of CO2 response curves revealed that CO2
      saturated assimilation rate, maximum rates of carboxylation and electron
      transport and respiration decreased with time. CO2-saturated assimilation rate
      was reduced by elevated O3 during the early stages of the season, while
      respiration was significantly greater under elevated CO2 as the crop approached
      maturity. The physiological origins of these responses and their implications for
      the performance of potato in a changing climate are discussed.

PMID- 11299016
TI  - Correlation of resistance and H2O2 production in Ulmus pumila and Ulmus
      campestris cell suspension cultures inoculated with Ophiostoma novo-ulmi.
AB  - The Dutch elm disease (DED) pathogen Ophiostoma novo-ulmi Buissm. elicited the
      production of H2O2 in cell suspension cultures of the resistant species Ulmus
      pumila L. This response was not observed in suspensions of the susceptible elm U.
      campestris Mill. H2O2 production started after a lag time of 30-40 min following
      inoculation, peaked between 4 and 6 h and lasted up to 24 h. Treatment of the
      suspensions with exogenously added H2O2 did not cause accumulation of the
      sesquiterpene phytoalexins mansonones nor of the coumarin scopoletin. Spore
      germination and growth of O. novo-ulmi were significantly delayed with different
      amounts of H2O2 (0.1-1 mM). These results suggest that H2O2 production is an
      inducible defence response which may contribute to DED resistance by delaying the
      growth of the pathogen at the earliest stages of infection. Whether H2O2 is
      involved in other elm defence responses to the pathogen is presently unknown, but
      its production seems to be an independent event from phytoalexin formation.

PMID- 11299017
TI  - Partial characterization of H-translocating inorganic pyrophosphatase from 3
      citrus varieties differing in vacuolar pH.
AB  - Vacuolar pyrophosphatase (V-PPase) from juice cells of 3 citrus varieties
      (differing in their vacuolar pH) were partially characterized using purified
      tonoplast vesicles. Total V-PPase activity was highest in vesicle samples from
      sweet limes with vacuolar pH of 5.0, while samples from acid limes (with lowest
      vacuolar pH of 2.0) had the minimal total V-PPase activity. Samples from
      'Valencia' orange had intermediate V-PPase levels. When assayed at equal V-PPase
      activity (measured as Pi production), V-PPase was not able to generate a pH
      gradient (DeltapH) in vesicles from acid lime, despite its capacity to form a
      DeltapH in the presence of ATP. Vesicles from sweet lime and 'Valencia' orange
      were able to form similar DeltapHs in the presence of PPi and ATP supplied
      together or separately. Antibodies raised against a peptide corresponding to the
      catalytic site of mung bean V-PPase reacted with samples from all varieties,
      coinciding with their capacity to hydrolyze PPi. However, antibodies raised
      against the entire V-PPase polypeptide from mung bean recognized V-PPase from
      sweet lime and 'Valencia' orange, but did not recognize acid lime samples even at
      elevated protein concentrations. The structural differences highlighted by
      antibody recognition, substrate affinity and proton-pumping reactions of V-PPase
      presented here may reflect evolutionary adaptations related to its reduced
      function under in vivo conditions and are in agreement with our understanding of
      acid, sugar accumulation and vacuolar pH changes during the development and
      maturation of citrus fruits.

PMID- 11299018
TI  - The inhibition of the carbon concentrating mechanism of the green alga Chlorella
      saccharophila by acetazolamide.
AB  - The effects of the carbonic anhydrase (CA) inhibitors acetazolamide (AZ) and
      dextran-bound sulfonamide (DBS) on HCO3--dependent O2 evolution in Chlorella
      saccharophila were evaluated. Addition of 4 uM AZ or 0.4 mg ml-1 DBS to
      photosynthesizing cells reduced the O2 evolution rate at low dissolved inorganic
      carbon (DIC) concentration, decreased the size of the intracellular acid-labile
      carbon pool, and decreased the apparent affinity of the cells for DIC.
      Measurement of the whole-cell affinity of cells for CO2 and HCO3- in the presence
      and absence of inhibitors indicated that active HCO3- transport was inhibited by
      AZ and DBS. The inhibition of HCO3- transport was independent of the inhibition
      of external and internal CA. These results suggest that the active uptake of HCO3
      occurs initially by the interaction of HCO3- and a CA-like transporter.

PMID- 11299019
TI  - Regulation of alcohol dehydrogenase gene expression in barley aleurone by
      gibberellin and abscisic acid.
AB  - The expression of the Adh1 gene (alcohol dehydrogenase, EC 1.1.1.1) was studied
      in the aleurone layer of barley (Hordeum vulgare cv. Himalaya). Expression
      increased markedly during grain development at the levels of activity, enzyme
      protein and mRNA. mRNA content, but not enzyme activity, could be increased
      further by exogenous abscisic acid (ABA) when isolated, de-embryonated developing
      grains were pre-treated with gibberellic acid (GA3) or fluridone. In isolated
      mature aleurone layers incubated with exogenous hormones, ADH mRNA was strongly
      up-regulated by ABA and down-regulated by GA3 within 6 h. With ABA, this increase
      in mRNA was followed by an increase in ADH protein and activity, peaking at 18 h.
      With GA3, the decrease in mRNA was accompanied by simultaneous decreases in
      protein and activity. In general, GA3 counteracted the effect of ABA and vice
      versa. In the aleurone of germinating grain, ADH activity decayed in a distal
      direction from the embryo, consistent with down-regulation by gibberellin(s)
      diffusing from it. It was concluded that ADH gene expression in the aleurone of
      the intact grain is regulated by an ABA/gibberellin interaction.

PMID- 11299020
TI  - Leaf senescence in a non-yellowing cultivar of chrysanthemum (Dendranthema
      grandiflora).
AB  - Chlorophyll (Chl) and total soluble protein decreased and proteolytic activity
      increased over a 12-day period during dark-induced senescence in detached leaves
      of Tara, a yellowing cultivar (Y) of Dendranthema grandiflora. In Boaldi, a non
      yellowing cultivar (NY), Chl and soluble protein remained near initial levels and
      little change in proteolytic activity was observed. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of soluble proteins showed no major
      differences in banding patterns between the two cultivars at day 0; however, all
      of the resolved proteins were diminished in Tara by day 12. On the other hand, in
      NY Boaldi, the intensity of the protein bands did not change over the 12-day
      period. Attached and detached leaves exhibited similar senescence patterns for
      each cultivar. Ethylene (100 ul l-1) accelerated the rate of Chl loss in detached
      leaves of Tara, but had no effect on Boaldi. These observations suggest that
      Boaldi is a stay-green genotype, possibly a functional type. The results are
      discussed in relation to the role of ethylene in chrysanthemum leaf senescence.

PMID- 11299021
TI  - Role of gibberellins in parthenocarpic fruit development induced by the genetic
      system pat-3/pat-4 in tomato.
AB  - The role of gibberellins (GAs) in the induction of parthenocarpic fruit-set and
      growth by the pat-3/pat-4 genetic system in tomato (Lycopersicon esculentum
      Mill.) was investigated using wild type (WT; Cuarenteno) and a near-isogenic line
      derived from the German line RP75/59 (the source of pat-3/pat-4 parthenocarpy).
      Unpollinated WT ovaries degenerated but GA3 application induced parthenocarpic
      fruit growth. On the contrary, parthenocarpic growth of pat-3/pat-4 fruits, which
      occurs in the absence of pollination and hormone treatment, was not affected by
      applied GA3. Unpollinated pat-3/pat-4 fruit growth was negated by paclobutrazol,
      an inhibitor of ent-kaurene oxidase, and this inhibitory effect was negated by
      GA3. The quantification of the main GAs of the early 13-hydroxylation pathway
      (GA1, GA8, GA19, GA20, GA29 and GA44) in unpollinated ovaries at 3 developmental
      stages (flower bud, FB; pre-anthesis, PR; and anthesis, AN), by gas
      chromatography-selected ion monitoring, showed that the concentration of most of
      them was higher in pat-3/pat-4 than in WT ovaries at PR and AN stages. The
      concentration of GA1, suggested previously to be the active GA in tomate, was 2-4
      times higher. Unpollinated pat-3/pat-4 ovaries at FB, PR and AN stages also
      contained relatively high amounts (5-12 ng g-1) of GA3, a GA found at less than
      0.5 ng g-1 in WT ovaries. It is concluded that the mutations pat-3/pat-4 may
      induce natural facultative parthenocarpy capacity in tomato by increasing the
      concentration of GA1 and GA3 in the ovaries before pollination.

PMID- 11299022
TI  - Intravenous immunoglobulin: regulatory perspectives on use and supply.
AB  - Technological advancements in the fractionation of plasma in the early 1970s led
      to the production of immunoglobulin preparations which could be administered
      intravenously. The ability to deliver larger doses than was possible with
      intramuscular products was accompanied by clinical studies demonstrating the
      efficacy of immunoglobulin treatment in a number of autoimmune and inflammatory
      conditions. This has led to a continuing increase in the usage of this product
      such that, currently, it is considered to be the driving force for plasma
      procurement. In recent years, difficulties have been experienced in the supply of
      this product in various markets. While intravenous immunoglobulins (IVIG) have
      undoubted clinical superiority over intramuscular products for the majority of
      indications, their use should be tempered with caution. Early clinical studies
      revealed that the risk of viral transmission from these products was higher than
      that of the traditional intramuscular presentation. This has had a profound
      impact on blood transfusion science as it has provided a major impetus for
      nucleic acid testing (NAT) for viral agents in blood donations. Perhaps less
      widely appreciated are the pressures which may be felt in blood services as the
      traditional drivers for plasma procurement - factor VIII and albumin - become
      secondary to IVIG. This review discusses the factors affecting the supply and
      safety of IVIG and the implications of recent global regulatory decisions on the
      delivery of this product and other therapeutic products derived from human
      plasma.

PMID- 11299023
TI  - The reduction of HIV transfusion risk in southern Brazil in the 1990s.
AB  - A retrospective study of blood donor records was undertaken to obtain risk
      estimates for transfusing HIV-contaminated blood due to an infectious window
      period in a large blood bank in the south of Brazil in the 1990s. An
      incidence/window period model was used to estimate HIV incidence and risk of
      seroconversion among 11 286 repeat donors with 8917 person-years of follow-up.
      Separate estimates were calculated for the periods of 1991-94, 1995-96 and 1997
      99. Although the residual risk of HIV-positive transfusion decreased from 1 :
      5000 in 1991-94 and 1 : 3794 in 1995-96 to 1 : 48 777 in 1997-99, this is still
      almost 10 times higher than in developed countries. The risk reduction is likely
      to have resulted from improved donor selection. Despite a 10-fold reduction in
      the risk of transfusing HIV-contaminated blood because of the screening test's
      failure to detect the virus during the infectious window period in the 1990s,
      additional measures are urgently needed to reduce the risk further. To this end,
      PCR screening of pooled blood donations might be considered in areas of high HIV
      prevalence when justified by cost-effectiveness calculations.

PMID- 11299024
TI  - Utilization of technologies to reduce allogeneic blood transfusion in the United
      States.
AB  - Concern over safety of the blood supply has led to the use of technologies to
      reduce allogeneic blood transfusion. The objective of this research was to
      determine the utilization of these technologies in the United States. We
      evaluated the following techniques: preoperative autologous donation (PAD), cell
      salvage (CS) and acute normovolemic haemodilution (ANH); and the following
      pharmaceuticals: aprotinin (APR), epsilon-aminocaproic acid (EACA), tranexamic
      acid (TXA), desmopressin (DDAVP) and recombinant human erythropoietin (EPO). In
      1997, we conducted a cross-sectional mail survey of service chiefs at 1000 US
      hospitals randomly selected and stratified by status as a provider of open-heart
      surgery, geographical location and hospital bed size. Sixty-nine per cent (690)
      of hospitals responded to at least one of the four surveys sent to each hospital.
      Hospitals reported use of techniques more than pharmaceuticals (P < 0.001); PAD
      (83%, n = 206) and CS (82% n = 420) were used most frequently. Lack of
      familiarity was the most common reason cited for infrequent use of
      pharmaceuticals. Organizational characteristics (e.g. provision of open-heart
      surgery, size, geographical location, teaching status and type of hospital) were
      differentially associated with technology use. There is greater use of techniques
      than pharmaceuticals in US hospitals to reduce the need for allogeneic blood in
      the peri-operative setting. Providing open-heart surgery is strongly associated
      with the utilization of these technologies.

PMID- 11299025
TI  - Transfusion practice in elective orthopaedic surgery.
AB  - . The transfusion requirements of 2233 patients who underwent total hip or knee
      joint arthroplasty procedures at nine Canadian hospitals during 1995-1996 were
      evaluated. Although 64% of patients were eligible for participation in an
      autologous blood donation (ABD) programme, only 8% predonated blood. Patients who
      were eligible for ABD were younger (62 years vs. 70 years) and had fewer medical
      illnesses (18% vs. 44%) than those who did not predonate. The rate of allogeneic
      transfusion was 9.0% (95% confidence interval 4.9-13.1%) in patients who
      predonated as compared with 24.1% (95% confidence interval 22.2-25.9%) in those
      who did not. Risk factors for the occurrence of an allogeneic transfusion were
      type of procedure (primary or revision hip arthroplasty), lower baseline
      haemoglobin, lower body weight, older age and presence of rheumatoid arthritis (P
      < 0.001). Only patients without risk factors were predicted to have a less than
      10% risk of receiving an allogeneic transfusion. Use of preventive strategies was
      minimal. Two models designed to predict the occurrence of an allogeneic
      transfusion were evaluated. If allogeneic transfusion rates are to be reduced,
      eligible patients should be encouraged to participate in ABD programmes. For
      patients who are ineligible, other preventative strategies should be introduced.

PMID- 11299026
TI  - Endogenous glutathione and platelet function in platelet concentrates stored in
      plasma or platelet additive solution.
AB  - Platelet function was studied in platelet concentrates by assay of the thrombin
      induced release of endogenous serotonin and presence of the swirling phenomenon
      in relation to endogenous glutathione (GSH) and cysteine. In platelets stored in
      plasma, addition of cysteamine resulted in only a moderate fall in GSH after 5
      days of storage, from an average of 14.91 to 11.46 nmol per 109 platelets.
      Exogenously added GSH had no effect, and addition of buthionine sulfoximine (BSO)
      resulted in almost complete depletion of GSH, to an average of 0.65 nmol per 109
      platelets. Addition of cysteamine or GSH resulted in increased endogenous
      cysteine whereas BSO had no effect. In platelets stored in a platelet additive
      solution (T-sol), complete depletion of GSH was found in the presence of
      cysteamine, GSH and BSO. Endogenous serotonin was unchanged during storage both
      in plasma and in additive solution (2.8 nmol per 109 platelets). Despite almost
      total depletion of endogenous GSH, the thrombin-induced release of serotonin
      after 5 days' storage was significantly affected only in the presence of BSO in
      platelets stored in additive solution (mean values 72.3% vs. 63.3% of endogeneous
      serotonin, P < 0.05). Similarly, addition of cysteamine or GSH had no significant
      effect on swirling but BSO reduced the swirling score after 5 days' storage in
      platelet additive solution compared with plasma. After 10 days' storage, there
      was a significant reduction in swirling in the concentrates where BSO was added
      (P < 0.05).

PMID- 11299027
TI  - Platelet storage in PAS-2 or autologous plasma: impact on functional parameters.
AB  - Currently, several platelet additive solutions for long-term platelet storage
      have been introduced. The aim of this study was to compare the deterioration of
      functional status of platelets stored for up to 5 days in autologous plasma (AP)
      only, with platelet stored in PAS-2, a salt solution containing acetate, citrate
      and sodium chloride. Change in platelet adhesion, aggregation and activation was
      measured by flow cytometric technique. In addition, beta-Thromboglobulin (beta
      TG), lactate and glucose were determined. After 5 days of storage, the expression
      of P-Selectin was significantly higher, the production of lactate and the
      consumption of glucose were significantly lower, in platelets stored in PAS-2
      than in autologous plasma. No significant differences were detected on day 5
      between the two groups with regard to fibrinogen, von Willebrand factor binding
      capacity, or to beta-TG release. It can be concluded that neither storage medium
      was consistently better for the parameters tested. However, it must be emphasized
      that platelets stored in autologous plasma exhibited less lesion, in terms of P
      Selectin expression compared with platelets stored in PAS-2.

PMID- 11299028
TI  - Isoimmune neonatal neutropenia due to anti-Fc(gamma) RIIIb antibody in a mother
      with an Fc(gamma) RIIIb deficiency.
AB  - A rare case of neutropenia in a newborn due to anti-Fc(gamma) RIIIb antibody is
      described. The newborn, born from the 5th pregnancy, had severe infection and no
      neutrophils. Full clinical and neutrophil count recovery was observed when the
      child was 5 weeks old. In maternal serum, panreactive granulocyte alloantibodies
      were detected. The mother's and her two sisters' granulocytes appeared to be
      Fc(gamma) RIIIb deficient as found using pheno- and genotyping methods. All of
      them were healthy. The anti-Fc(gamma) RIIIb specificity of antibodies was
      identified by the monoclonal antibody immunobilization of neutrophil antigen
      assay. Such antibodies were not found in both sisters with the Fc(gamma) RIIIb
      deficiency, although they were pregnant, one of them on the seventh occasion.

PMID- 11299029
TI  - Universal leukodepletion of blood and febrile transfusion reactions.

PMID- 11299030
TI  - HCV-RNA screening in a medium size Italian transfusion service using a commercial
      PCR method: one year's experience.

PMID- 11299031
TI  - Safeguarding developing countries' rights to affordable medicines for HIV/AIDS:
      how effective are international trade rules?

PMID- 11299032
TI  - The unreliability of the Kato-Katz technique limits its usefulness for evaluating
      S. mansoni infections.
AB  - The Kato-Katz technique, a (semi) quantitative stool examination technique, is
      generally recommended for diagnosis and evaluation of Schistosoma mansoni
      infection by schistosome experts. However, egg counts are subject to important
      variability. In order to quantify the reproducibility of egg counts using the
      Kato-Katz technique, field data of 1255 observations on 299 subjects infected
      with Schistosoma mansoni were analysed. Agreement between repeated observations
      was assessed both categorically (kappa statistic) and continuously (analysis of
      variance). The day-to-day variation of egg counts was much greater than the
      variation due to different observers or different slides. The quantitative
      reproducibility was low: the weighted kappa statistic was 0.39 between specimens
      of different days, 0.62 between slides of the same specimen and 0.81 between
      observers of the same slide. Therefore the classification of individual patients
      into groups based on egg counts, used as a measure of morbidity, must be
      interpreted with great care, especially in longitudinal studies. Usefulness of
      the Kato-Katz technique appears limited. Its reproducibility is low. It cannot be
      recommended as a routine test in a primary health care setting or in a hospital
      laboratory because safety and detection of other parasites are better assured by
      other techniques. It can be used in epidemiological studies and evaluation of
      schistosomiasis control programmes, but here too, other techniques might be
      preferred.

PMID- 11299033
TI  - Dengue transmission risk maps of Argentina.
AB  - Dengue is an emerging disease that has become important in Argentina because of
      its vector's presence (Aedes aegypti) and its endemicity in neighbouring
      countries. Thematic maps were built for Argentina considering four main factors:
      population susceptibility to dengue virus infection (population density);
      entrance of the virus from endemic countries (main roads and airports);
      conditions for the vector (urbanization, altitude, minimum, maximum and mean
      daily temperatures) and virus extrinsic incubation period (EIP) completion in the
      mosquito before its death. EIP duration was modelled with a temperature-dependent
      function and considering life expectancies of 10, 15 and 20 days for the adult
      mosquito. The results show maximum risk of dengue transmission in the northern
      and north-eastern part of the country year-round and in the centre during the
      summer. Although life expectancy of the adult mosquito has a considerable
      influence on EIP completion, the north-east to south-west decreasing gradient is
      maintained. Assuming 20-day life expectancy, the EIP would be completed in almost
      any region of the country; whereas with 15-day life expectancy it would be
      limited to vector distribution area, and at 10 days it would be restricted to the
      northern extreme of the country.

PMID- 11299034
TI  - Intestinal parasitic diseases in Riyadh, Saudi Arabia: prevalence,
      sociodemographic and environmental associates.
AB  - Our objectives were to assess the prevalence of intestinal parasitic infections
      in Riyadh and to determine associated sociodemographic and environmental factors.
      The study was conducted through a household survey. Three health centres were
      chosen from each of the five Riyadh urban regions and 15 from rural areas. Based
      on the average family size, a random sample of households were chosen. All
      household members were asked to participate in the study. Data were collected
      using a pre-designed questionnaire eliciting data on sociodemographic and
      environmental factors. A stool specimen of each individual was examined
      microscopically for the presence of trophozoites and cysts. Six thousand and
      twelve participants with a mean age of 23.3 +/- 17.4 (median 19 years, 48.6%
      males) were studied and 32.2% were infected. The infection rate was high in urban
      areas (33.3%), among children < 12 years (34.4%), non-Saudis (42.2%), single
      persons (34.9%), illiterate individuals (33.8%), those who obtained drinking
      water from tankers (36.1%) and those who disposed of sewage in open channels
      (47.1%). Stratified analysis showed that for Saudis <12 years parasitic
      infections were significantly higher among tanker users (39.5%) and septic tank
      users (36.8%). For Saudis> or =12 years low education, water storage and open
      sewage disposal were statistically associated with parasitic infections (P <
      0.05). Among expatriates, infections were high among males (47.6%), urban
      residents (48.3%), single persons (46.9%), tanker users (39.5%) and septic tank
      users (78.6%). Multivariate logistic regression analysis showed that age < 12
      years, non-Saudi nationalities, educational level below secondary school, tanker
      as source of water and open sewage disposal were independently associated with
      high intestinal parasitic infection.

PMID- 11299035
TI  - The impact of 34 years of massive DEC chemotherapy on Wuchereria bancrofti
      infection and transmission: the Maupiti cohort.
AB  - Semi-annual mass DEC chemotherapy combined with vector control at the beginning
      of the programme, has been administered on the remote island of Maupiti (French
      Polynesia) since 1955 (except two periods in 1960-67 and 1970-74). The results of
      two surveys in 1985 and 1989, reporting 0% microfilaraemia, led to the hope that
      the eradication of lymphatic filariasis had been achieved. We combined
      parasitological criteria (microfilaraemia by membrane filtration), immunological
      (antigenaemia and serum levels of specific IgG antibodies) and molecular (PCR
      based evaluation of infection in mosquitoes) techniques and found only good
      control of the parasite: We found residual microfilaraemia in 0.4% of the sample
      (mean level in carriers: 101.2 mf/ml), antigenaemia in 4.6% (mean level in
      positive persons: 714.4 units/ml) and specific IgG in 21.6% (including in one
      very young child). In addition, an infection rate of 1.4% was calculated in the
      Aedes polynesiensis vector population. These data, obtained in 1997 just before a
      hurricane, were partially confirmed in 1999 (0.1% of infection rate in the
      vector). Together with the possibility of some resistance to DEC, various
      epidemiological factors critical for the eradication of lymphatic filariasis are
      discussed.

PMID- 11299036
TI  - Rapid therapeutic response onset of a new pharmaceutical form of chloroquine
      phosphate 300 mg: effervescent tablets.
AB  - OBJECTIVE: To compare the efficiency, safety and taste of two pharmaceutical
      forms of chloroquine phosphate 300 mg: effervescent tablets against uncoated
      tablets. METHOD: An open randomized study with 60 adults who suffered from acute
      uncomplicated Plasmodium falciparum malaria in three health centres in Nkongsamba
      health district, Cameroon. RESULTS: Mean times to fever clearance, symptoms
      clearance and asexual parasites clearance were longer in the uncoated tablets
      group: 36 h (range 24-48 h, SD = 16.8) vs. 60 h (range 24-96 h, SD = 31.2, P =
      0.001) for fever clearance, 36 h (24-48 h, SD = 16.8) vs. 48 h (24-72, SD = 24, P
      = 0.001) for symptoms clearance and 48 h (24-72, SD = 1) vs. 72 h (48-96, SD =
      24, P = 0.001) for parasitaemia clearance. Uncoated tablets took significantly
      longer to achieve 50% reduction of the initial asexual parasite density:
      (mean/SD) 19.2 h/7 vs. 52.8 h/16.8, P < 0.00001. The adverse effects in the two
      groups were similar, P > 0.05. The cure rate at day 7 in the two groups was
      similar, P > 0.05. There was no chloroquine resistance in the effervescent
      tablets group but one RI and one RII resistance in the uncoated tablets group.
      The taste of the two pharmaceutical forms was significantly different, P <
      0.00001. Effervescent tablets tasted sweet (score = 7.93), whereas uncoated
      tablets were bitter (score = 2.07). CONCLUSION: Effervescent tablets of
      chloroquine phosphate 300 mg work faster than uncoated tablets and because of
      their safe use and sweet taste achieve good therapeutic compliance.

PMID- 11299037
TI  - Sexually transmitted infections and associated socio-demographic and behavioural
      factors in women seeking primary care suggest Madagascar's vulnerability to rapid
      HIV spread.
AB  - OBJECTIVES: To examine sexually transmitted infections (STIs) and associated
      socio-demographic and behavioural factors in women seeking care for genital
      discharge syndrome in Antananarivo, Madagascar. METHODS: One thousand and sixty
      six consecutive symptomatic women were interviewed and examined; bacterial
      vaginosis (BV), vulvovaginal candidiasis, trichomoniasis (TV), cervical infection
      (CI) due to chlamydial or gonococcal infections, and syphilis seroreactivity were
      determined by laboratory diagnosis. Associations between STIs and individual
      characteristics were evaluated using bivariate and logistic regression analyses.
      RESULTS: The prevalence of BV, TV, CI, and syphilis seroreactivity was,
      respectively, 85%, 16%, 49%, 16% in 94 prostitutes; 70%, 18%, 30%, 13% in 96
      occasional sex traders; and 53%, 24%, 17%, and 4% in 876 general women. CI was
      independently and positively associated with a symptomatic partner, new sex
      partner in last 3 months, unfaithful partner, prostitution, joblessness and being
      < 25 years old. Syphilis was associated with low schooling, young age at coital
      debut, sex trading, and > 1 sex partner in the previous 3 months. CONCLUSIONS:
      These high STI rates and associated characteristics suggest the local
      vulnerability to rapid HIV spread and show the need for prevention efforts that
      involve youth, prostitutes, occasional sex traders, sex clients, and men who have
      concurrent sexual partnerships.

PMID- 11299038
TI  - Epidemiological and ecological characteristics of past dengue virus infection in
      Santa Clara, Peru.
AB  - To determine risk factors associated with dengue (DEN) virus infection among
      residents of Santa Clara, Peru, a rural Amazonian village near Iquitos, a cross
      sectional serological, epidemiological and environmental survey was conducted.
      Demographic, social and behavioural information was obtained by standardized
      questionnaire from 1225 Santa Clara residents (61.3%) aged 5 years or older.
      Additional data were obtained on the environmental variables and immature
      mosquito species and abundance surrounding each household (n = 248). Sera that
      had been collected previously by the Peruvian Ministry of Health from residents
      were tested by an enzyme-linked immunosorbent assay (ELISA) for DEN virus IgG
      antibody. Antibody identity was verified as DEN by plaque reduction
      neutralization test. Data on individuals were analysed by univariate and
      multivariable methods, and independent sample t-tests. Spatial clustering was
      evaluated by comparing distances among DEN positive households. Overall, antibody
      prevalence was 29.4 % and more than doubled from the youngest to the oldest age
      groups, but did not differ by sex. Curiously, length of residence in Santa Clara
      was negatively associated with DEN virus antibodies. More frequent travel to
      Iquitos was positively associated with seroprevalence. Residents who obtained
      water from a river source rather than a local well also had significantly higher
      antibody prevalence. None of the environmental variables measured at each
      household corresponded to the patterns of antibody distribution. Of the larval
      mosquitoes found around residences, all were determined to be species other than
      Aedes. No evidence of spatial autocorrelation among antibody-positive households
      was detected. These results strongly suggested that recent DEN virus transmission
      did not occur in the village and that most infections of residents of this rural
      village were acquired while visiting the city of Iquitos.

PMID- 11299039
TI  - Detection of IgG in cerebrospinal fluid for diagnosis of neurocysticercosis:
      evaluation of saline and SDS extracts from Taenia solium and Taenia crassiceps
      metacestodes by ELISA and immunoblot assay.
AB  - We compared saline (S) and sodium dodecyl sulphate (SDS) extracts from Taenia
      solium (homologous species - HO) and Taenia crassiceps (heterologous species -
      HE) metacestodes in order to detect IgG by ELISA and immunoblot assay (IBA) in
      cerebrospinal fluid (CSF) for the diagnosis of human neurocysticercosis (NC). CSF
      samples were obtained from 93 patients. Of these, 40 had NC, five had a diagnosis
      of probable NC, nine had central nervous system schistosomiasis or
      strongyloidiasis and 39 had other neurological alterations. Samples were analysed
      by ELISA and the results were compared with IBA in all samples with confirmed and
      probable NC diagnosis, in all samples with other central nervous system parasitic
      infection, and in 10 of those with another neurological alterations. ELISA
      sensitivity was 100%, 85%, 95% and 87.5% for the S-HO, S-HE, SDS-HO and SDS-HE
      extracts, respectively, and ELISA specificity was 100% for S-HO, S-HE, SDS-HO
      extracts and 97.9% for SDS-HE antigen. Immunodominant peptides detected by IBA
      were, by decreasing percentage of recognition: 64-68 and 45 kDa for S-HO; 108
      114, 92-95, 64-68, 83 and 88 kDa for S-HE; 64-68, 108-114, 77 and 86 kDa for SDS
      HO; and 108-114, 88 and 92-95 kDa for SDS-HE. Overall the homologous antigenic
      extracts showed higher sensitivity than the heterologous extracts in the
      diagnosis of NC in CSF samples. The heterologous extracts contained most of the
      immunodominant peptides presented in the homologous extracts, which are
      recognized by IgG antibodies in CSF samples.

PMID- 11299040
TI  - School enrollment in Zanzibar linked to children's age and helminth infections.
AB  - School health programmes have been identified as a cost-effective strategy to
      reduce morbidity due to soil-transmitted helminths in the school-age population,
      but the low rate of school enrollment in developing countries is a major factor
      limiting their success. OBJECTIVE: The present study was conducted to identify
      reasons for non-enrollment and to evaluate differences in the occurrence of
      helminth infection between enrolled and non-enrolled children in Zanzibar, United
      Republic of Tanzania. METHOD: A questionnaire was submitted to 520 households to
      obtain information about enrollment and other socio-economic indicators. In
      addition, one school-age child was randomly selected in each household and
      investigated for soil-transmitted helminth infection. RESULTS: Overall, 71% of
      school-age children were enrolled. Enrollment increased with age. Only 41% of
      children under 9 years of age were enrolled compared to 91% in children older
      than 12 years. Enrollment is delayed because of an insufficient number of
      schools. Among non-enrolled school-age children, the proportion of heavy
      intensity infections was twice that of enrolled school-age children. CONCLUSIONS:
      Most of the non-enrolled school-age children live together with enrolled siblings
      in the same household, thereby representing an important opportunity for
      effective outreach activities. The effectiveness of the school-based helminth
      control programme in reducing the intensity of infection was confirmed. The
      significant gains achieved by enrolled school-age children in this study must be
      viewed as an attainable goal for the important numbers of non-enrolled school-age
      children in endemic areas. Decision-makers must ensure that outreach activities
      are included in helminth control programmes targeted to school-age children.

PMID- 11299041
TI  - Community-directed treatment of onchocerciasis with ivermectin in Takum, Nigeria.
AB  - A study to identify factors within the community that can ensure sustainable
      community-directed treatment (ComDT) with ivermectin compared the effectiveness
      of programme-designed (PD) and community-designed (CD) strategies in 37 villages
      in the Takum area of Nigeria. In a subset of PD villages, designated PD1,
      communities were asked to use the village heads as community-directed
      distributors (CDD), and the other communities (PD2) were asked to select female
      distributors, and both were instructed to use the house-to-house method of
      distribution. Community-designed communities, on the other hand, were asked to
      design their own approach. All study communities received health education,
      treatment guidelines, and training enabling them to determine appropriate dosage.
      A total of 1744 people were interviewed about their experiences after two
      treatment cycles. Communities preferred honest, reliable community members as
      CDDs, but few women were selected. The results show striking similarity between
      PD and CD villages in many respects. In the PD1 villages, where the programme
      designated the village head as CDD, the mode of distribution was changed from
      house-to-house to central point, and distribution took place in the compound of
      the village head. In the PD2 villages, where the programme specified distributors
      should be women, the women who were selected were replaced by their male
      children. These changes to the original design were consistent with the local
      cultural norms and made the arrangement for distribution more acceptable to the
      people. Programme-designed villages that used the village head as distributors
      performed better than those that used women, and the coverage in the former group
      compares well with that of CD villages. Only five villages achieved coverage >
      60%, but dosage was correct in most cases (87.4%). Drug shortage was the most
      frequent reason for non-treatment. Communities devised means for ensuring equity
      and fairness in sharing their limited supply and freely altered the original
      designs to fit local norms and values. These changes to the original design were
      consistent with local norms and were acceptable to the people. The success of
      this strategy should be tested in other parts of Nigeria. Long-term success of
      ComDT, however, requires a reliable drug supply and inputs from professionals in
      the health system for minimal supervision. The core issues that determine
      sustainability of ComDT appear to be not so much in the structure, but in the
      process by which they are introduced. Communities will only sustain a programme
      where the process of implementation fits well with local norms and where
      communities are free to alter PD procedures that are inconsistent with local
      customs.

PMID- 11299042
TI  - Cre reporter strains produced by targeted insertion of EYFP and ECFP into the
      ROSA26 locus.
AB  - BACKGROUND: Several Cre reporter strains of mice have been described, in which a
      lacZ gene is turned on in cells expressing Cre recombinase, as well as their
      daughter cells, following Cre-mediated excision of a loxP-flanked transcriptional
      "stop" sequence. These mice are useful for cell lineage tracing experiments as
      well as for monitoring the expression of Cre transgenes. The green fluorescent
      protein (GFP) and variants such as EYFP and ECFP offer an advantage over lacZ as
      a reporter, in that they can be easily visualized without recourse to the vital
      substrates required to visualize beta-gal in living tissue. RESULTS: In view of
      the general utility of targeting the ubiquitously expressed ROSA26 locus, we
      constructed a generic ROSA26 targeting vector. We then generated two reporter
      lines of mice by inserting EYFP or ECFP cDNAs into the ROSA26 locus, preceded by
      a loxP-flanked stop sequence. These strains were tested by crossing them with
      transgenic strains expressing Cre in a ubiquitous (beta-actin-Cre) or a cell
      specific (Isl1-Cre and En1-Cre) pattern. The resulting EYFP or ECFP expression
      patterns indicated that the reporter strains function as faithful monitors of Cre
      activity. CONCLUSIONS: In contrast to existing lacZ reporter lines, where lacZ
      expression cannot easily be detected in living tissue, the EYFP and ECFP reporter
      strains are useful for monitoring the expression of Cre and tracing the lineage
      of these cells and their descendants in cultured embryos or organs. The non
      overlapping emission spectra of EYFP and ECFP make them ideal for double labeling
      studies in living tissues.

PMID- 11299043
TI  - The A54T polymorphism at the intestinal fatty acid binding protein 2 is
      associated with insulin resistance in glucose tolerant Caucasians.
AB  - BACKGROUND: An A54T polymorphism at the fatty acid binding protein 2 (FABP2)
      locus was found to be associated with insulin resistance in non-diabetic Pima
      Indians. To see whether this association is present in other populations, we
      performed a cross sectional study to examine the role of this polymorphism on
      insulin resistance in 55 healthy and normotensive Caucasian subjects with normal
      glucose tolerance. Insulin sensitivity (%S) and beta cell function (%B) were
      assessed using the Homeostasis Model Assessment (HOMA). Their genotypes were
      determined using a polymerase chain reaction-restriction fragment length
      polymorphism assay. The relationship between the genotypes and the phenotypes was
      examined. RESULTS: After genotyping, we identified 24 AA, 27 AT and 4 TT
      subjects. The TT subjects were combined with the AT subjects during the analysis
      due to its small sample size. No differences were noted in gender distribution,
      clinical features, and fasting lipid profile between the two genotypic groups (AA
      vs. AT/TT). The AT/TT group had a higher fasting plasma insulin concentration and
      a lower %S than the AA group (p = 0.0444 and p = 0.0461, respectively). However,
      no differences were noted in plasma glucose concentrations and %B. Univariate
      analysis revealed that this polymorphism explained 7.3% of the variation in %S.
      Multivariate analysis revealed that the polymorphism was an independent
      determinant for %S (p = 0.0434) and with body mass index accounted for 28.7% of
      the variation in %S. In contrast, this polymorphism had no impact on %B.
      CONCLUSIONS: The A54T polymorphism at the FABP2 locus is a risk factor for
      insulin resistance in a Caucasian population.

PMID- 11299044
TI  - A tandem repeats database for bacterial genomes: application to the genotyping of
      Yersinia pestis and Bacillus anthracis.
AB  - BACKGROUND: Some pathogenic bacteria are genetically very homogeneous, making
      strain discrimination difficult. In the last few years, tandem repeats have been
      increasingly recognized as markers of choice for genotyping a number of
      pathogens. The rapid evolution of these structures appears to contribute to the
      phenotypic flexibility of pathogens. The availability of whole-genome sequences
      has opened the way to the systematic evaluation of tandem repeats diversity and
      application to epidemiological studies. RESULTS: This report presents a database
      (http://minisatellites.u-psud.fr) of tandem repeats from publicly available
      bacterial genomes which facilitates the identification and selection of tandem
      repeats. We illustrate the use of this database by the characterization of
      minisatellites from two important human pathogens, Yersinia pestis and Bacillus
      anthracis. In order to avoid simple sequence contingency loci which may be of
      limited value as epidemiological markers, and to provide genotyping tools
      amenable to ordinary agarose gel electrophoresis, only tandem repeats with repeat
      units at least 9 bp long were evaluated. Yersinia pestis contains 64 such
      minisatellites in which the unit is repeated at least 7 times. An additional
      collection of 12 loci with at least 6 units, and a high internal conservation
      were also evaluated. Forty-nine are polymorphic among five Yersinia strains
      (twenty-five among three Y. pestis strains). Bacillus anthracis contains 30
      comparable structures in which the unit is repeated at least 10 times. Half of
      these tandem repeats show polymorphism among the strains tested. CONCLUSIONS:
      Analysis of the currently available bacterial genome sequences classifies
      Bacillus anthracis and Yersinia pestis as having an average (approximately 30 per
      Mb) density of tandem repeat arrays longer than 100 bp when compared to the other
      bacterial genomes analysed to date. In both cases, testing a fraction of these
      sequences for polymorphism was sufficient to quickly develop a set of more than
      fifteen informative markers, some of which show a very high degree of
      polymorphism. In one instance, the polymorphism information content index reaches
      0.82 with allele length covering a wide size range (600-1950 bp), and nine
      alleles resolved in the small number of independent Bacillus anthracis strains
      typed here.

PMID- 11299045
TI  - Flow cytometry analysis of the effect of allopurinol and the dinitroaniline
      compound (Chloralin) on the viability and proliferation of Leishmania infantum
      promastigotes.
AB  - BACKGROUND: Leishmaniasis is a major parasitic disease in the tropical regions.
      However, Leishmania infantum has recently emerged as a very important cause of
      opportunistic infections for individuals positive for human immunodeficiency
      virus (HIV). However, there is a lack of in vitro tests for assessing the effect
      of anti-parasitic drugs on the viability and proliferation of Leishmania
      infantum. The aim of this study is to assess the efficacy of anti-parasitic drugs
      like allopurinol and Chloralin on the viability and proliferation of L. infantum
      promastigotes by utilizing two complementary flow cytometric approaches after
      exposure of the promastigotes to various concentrations of the drugs. RESULTS:
      The density of the cultures in the presence and absence of allopurinol was
      determined by haemocytometer enumeration. The two flow cytometric approaches used
      to monitor the drug effect were: (i) a quantitative method to measure cell
      division using 5-,6-carboxyfluorescein diacetate succinimidyl ester (CFSE)
      staining and (ii) evaluation of cell viability by dual-staining with the membrane
      permeable nuclear stain, SBRY-14 and propidium iodide. It was found that
      concentrations of allopurinol above 50 microg/ml yielded a clear decrease in the
      proliferation rate of the promastigotes. However, the viability results showed
      that about 46.8% of the promastigotes incubated in the presence of 800 microg/ml
      of allopurinol were still alive after 96 hours. In sharp contrast, more than 90%
      of promastigotes treated with Chloralin 10 microM (2.7 microg/ml) were dead after
      48 hours of treatment. These flow cytometric findings suggest that allopurinol
      has a leishmaniostatic effect while the dinitroaniline compound (Chloralin) has a
      leishmaniocidal effect against promastigotes. CONCLUSIONS: The flow cytometric
      data on proliferation and viability were consistent with results obtained from
      haemocytometer counts and allowed us to develop a model for assessing in vitro
      the effects of medicaments like allopurinol and chloralin on L. infantum
      promastigotes on a cellular level.

PMID- 11299046
TI  - Practice and professional development plans (PPDPs): results of a feasibility
      study.
AB  - BACKGROUND: Dissatisfaction with uniprofessional education structures as a means
      of improving the quality of healthcare has led to proposals to develop ways of
      integrating professional learning and organisational development. AIMS: Test the
      feasibility of introducing practice and professional development plans using a
      centrally sponsored project in Wales. DESIGN: Qualitative observational study.
      STUDY SAMPLE: All 541 practices in Wales were alerted to the project and invited
      to apply. A selection process was suggested to Health Authorities but not always
      efficiently conducted: 23 practices were selected and 18 participated in the
      process. METHOD: Central funding was made available to health authorities. The
      project framework was designed by an educational department and conceptualised as
      the development of personal portfolios linked to one key organisation change in
      each practice, facilitated by external consultants who would typically hold
      workshops or other events. An independent researcher using non-participant
      observation techniques at workshops and practices undertook documentary analysis
      and fieldwork in four health authorities. RESULTS: Difficulties were encountered
      with the process of implementing the project: marketing and practice selection
      inconsistencies delayed the work and it was difficult to recruit practices into
      the project. The lack of experienced individuals to do the work and practitioner
      suspicion about perceived 'management' agendas were significant problems. After
      initial hesitancies most practices appreciated the value of developing wider
      ownership and commitment to proposed practice changes. Organisations found it
      difficult to support individual completion of the personal portfolio component of
      the plans. The ability to develop systems for clinical services was dependent on
      having already established a culture of effective teamwork in the organisation.
      CONCLUSIONS: This work supports the view that organisational development has
      considerable potential for bringing about effective change, and individual
      contributions could form a valuable component of personal portfolios. We believe
      that the existing structures in education and management in the health service
      are not yet able to support these processes. Evidence from the fields of risk
      management and quality improvement all point to the need to develop effective
      organisational systems and the results of this feasibility study indicate that
      alternative models of sustaining organisational development need careful
      evaluation.

PMID- 11299047
TI  - Polymorphisms in the Mn-SOD and EC-SOD genes and their relationship to diabetic
      neuropathy in type 1 diabetes mellitus.
AB  - BACKGROUND: Oxidative stress, resulting in a marked increase in the level of
      oxygen free radicals (OFR), has been implicated in the etiology of diabetic
      neuropathy (DN). Antioxidant enzymes may protect against the rapid onset and
      progression of DN, by reducing the excess of OFR and peroxide. Mutations and
      polymorphisms in the genes encoding such enzymes may therefore result in
      predisposition to DN. We investigated the role of genes encoding two antioxidant
      enzymes, mitochondrial (Mn-SOD) and extracellular (EC-SOD) superoxide dismutase,
      in DN pathogenesis in a Russian population. We studied Ala(-9)Val and Ile58Thr
      polymorphisms of the Mn-SOD gene and Arg213Gly dimorphism of the EC-SOD gene in
      type 1 diabetic patients with (n = 82) and without DN (n = 84). RESULTS: We
      developed and used a new polymerase chain reaction (PCR) assays for rapid
      detection of polymorphisms. These assays involved the use of mismatch PCR primers
      to create restriction sites in the amplified product only in presence of the
      polymorphic base. The PCR product was than digested with BshTI, Eco32I or Eco52I
      to detect Ala(-9)Val, Ile58Thr or Arg213Gly polymorphic site respectively. The
      frequencies of the Ala allele (50.6% vs. 68.5%, p < 0.002) and the Ala/Ala
      genotype (17.1% vs. 39.3%, p < 0.005) of the Mn-SOD gene were significantly lower
      in DN patients than in diabetic subjects without DN. In contrast, the Val allele
      (49.4% vs. 31.5%, p < 0.002) and the Val/Val genotype (15.9% vs. 2.4%, p < 0.01)
      were significantly more frequent in the DN patients than in the control group.
      CONCLUSIONS: Ala(-9)Val substitution in the Mn-SOD gene was associated with DN in
      a Russian population

PMID- 11299048
TI  - Genetic studies of the Roma (Gypsies): a review.
AB  - BACKGROUND: Data provided by the social sciences as well as genetic research
      suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best
      described as a conglomerate of genetically isolated founder populations. The
      relationship between the traditional social structure observed by the Roma, where
      the Group is the primary unit, and the boundaries, demographic history and
      biological relatedness of the diverse founder populations appears complex and has
      not been addressed by population genetic studies. RESULTS: Recent medical genetic
      research has identified a number of novel, or previously known but rare
      conditions, caused by private founder mutations. A summary of the findings,
      provided in this review, should assist diagnosis and counselling in affected
      families, and promote future collaborative research. The available incomplete
      epidemiological data suggest a non-random distribution of disease-causing
      mutations among Romani groups. CONCLUSION: Although far from systematic, the
      published information indicates that medical genetics has an important role to
      play in improving the health of this underprivileged and forgotten people of
      Europe. Reported carrier rates for some Mendelian disorders are in the range of 5
      15%, sufficient to justify newborn screening and early treatment, or community
      based education and carrier testing programs for disorders where no therapy is
      currently available. To be most productive, future studies of the epidemiology of
      single gene disorders should take social organisation and cultural anthropology
      into consideration, thus allowing the targeting of public health programs and
      contributing to the understanding of population structure and demographic history
      of the Roma.

PMID- 11299049
TI  - Osmotic stress-dependent serine phosphorylation of the histidine kinase homologue
      DokA.
AB  - BACKGROUND: Two-component systems consisting of histidine kinases and their
      corresponding receivers are widespread in bacterial signal transduction. In the
      past few years, genes coding for homologues of two-component systems were also
      discovered in eukaryotic organisms. DokA, a homologue of bacterial histidine
      kinases, is an element of the osmoregulatory pathway in the amoeba Dictyostelium.
      The work described here addresses the question whether DokA is phosphorylated in
      vivo in response to osmotic stress. RESULTS: We have endogenously overexpressed
      individual domains of DokA to investigate post-translational modification of the
      protein in response to osmotic shock in vivo. Dictyostelium cells were labeled
      with [32P]-orthophosphate, exposed to osmotic stress and DokA fragments were
      subsequently isolated by immunoprecipitation. Thus, a stress-dependent
      phosphorylation could be demonstrated, with the site of phosphorylation being
      located in the kinase domain. We demonstrate biochemically that the
      phosphorylated amino acid is serine, and by mutational analysis that the
      phosphorylation reaction is not due to an autophosphorylation of DokA.
      Furthermore, mutation of the conserved histidine did not affect the osmostress
      dependent phosphorylation reaction. CONCLUSIONS: A stimulus-dependent serine
      phosphorylation of a eukaryotic histidine kinase homologue was demonstrated for
      the first time in vivo. That implies that DokA, although showing typical
      structural features of a bacterial two-component system, might be part of a
      eukaryotic signal transduction pathway that involves serine/threonine kinases.

PMID- 11299050
TI  - The beginning of the research stream in family medicine residency program at
      McMaster University.
AB  - BACKGROUND: To examine research background, attitudes, knowledge and skills of
      family medicine residents with regard to primary care research and to compare
      residents who elected to participate in the research stream with those who did
      not. METHODS: Mailed survey of Family Medicine residents at McMaster University
      in 1998, 70% (52/74) of whom responded. The main outcome measures consisted of
      research background; attitudes towards primary care research and research
      activities during residency program; knowledge and skills in applying it in
      biostatistics, epidemiology, and research design. RESULTS: The vast majority of
      the residents reported previous research experience and/or some training in
      epidemiology and biostatistics. Residents in the research stream were more likely
      to be female and were positive towards primary care research: they were more
      interested in research, more interested in obtaining more research training while
      a resident, and placed more importance on developing research early in medical
      education. The research stream residents had stronger views regarding perceived
      lack of support staff and lack of time for research. There were no statistically
      significant differences between the research stream and other residents in terms
      of research knowledge and skills in applying it. CONCLUSIONS: Attitudes towards
      research rather than research knowledge or skills seemed to distinguish those
      selecting to be in our new research stream at the inception.

PMID- 11299051
TI  - Estimates of complications of medical care in the adult US population.
AB  - BACKGROUND: Total US population estimates of complications of medical care have
      relied on extrapolations of state-specific estimates. Generalizability is suspect
      because findings are limited by geographical location or time. We describe the
      relationship between the annual prevalence of complications of medical care (CM)
      and socio-demographic characteristics in the adult US population. METHODS: We
      used data from the National Health Interview Surveys, annual nationwide surveys
      of the resident, civilian, noninstitutionalized population of the United States.
      The main outcome of interest was self-reported conditions from CMs (ICD-9 996
      999) and activity limitations that arise from such events. Univariate estimates
      and multivariably adjusted models accounting for selected socio-demographic
      characteristics and health status were derived. RESULTS: A total of 618,167
      reports of conditions from 313,438 subjects 18 years and older from 1987 to 1994
      were examined. In 1987, 830,386 adults reported complications of medical care,
      increasing by about 40% to 1,174,089 adults in 1994. Based on an extrapolation to
      the US adult population, rates increased by 25% from 558 to 678 per 100,000
      during the same period. One-third reported onset a year prior to the interview;
      two-thirds visited a doctor six months prior; half experienced limitation in
      major activities; a quarter reported limitation in personal care activities. In
      the two weeks preceding the interview, complications of medical care caused an
      average of 1.72 days of restricted activity, 0.79 days spent in bed, and 0.58
      days of work lost. Race modified the age-specific risk of these complications.
      CONCLUSIONS: Complications of medical care impose heavier morbidity than
      previously considered with some indication that socio-demographic variables
      modify the risk for injuries.

PMID- 11299052
TI  - T-cell-mediated control of autoimmunity.
AB  - Inflammatory responses provoked by pathogens are antigen-specific in their
      induction but are nonspecific in their effects. Consequently, they are
      potentially damaging to the host that produces them. In addition, the immune
      system can respond specifically to self antigens, thereby giving rise to
      autoimmune diseases. A number of regulatory mechanisms have evolved to prevent
      such adverse effects. One of these has been shown to depend on a particular
      subset of CD4+ T cells that appears to have evolved specifically for this
      protective role. These cells are termed regulatory T cells. This review
      summarises what is known about them.

PMID- 11299053
TI  - The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2
      paradigm in autoimmunity.
AB  - The classification of T helper cells into type 1 (Th1) and type 2 (Th2) led to
      the hypothesis that Th1 cells and their cytokines (interleukin [IL]-2, interferon
      [IFN]-gamma) are involved in cell-mediated autoimmune diseases, and that Th2
      cells and their cytokines (IL-4, IL-5, IL-10, IL-13) are involved in
      autoantibody(humoral)-mediated autoimmune diseases. However, this paradigm has
      been refuted by recent studies in several induced and spontaneous mouse models of
      systemic lupus erythematosus, which showed that IFN-gamma is a major effector
      molecule in this disease. These and additional findings, reviewed here, suggest
      that these two cross-talking classes of cytokines can exert autoimmune disease
      promoting or disease-inhibiting effects without predictability or strict
      adherence to the Th1-versus-Th2 dualism.

PMID- 11299054
TI  - Future of adenoviruses in the gene therapy of arthritis.
AB  - Recombinant adenoviruses are straightforward to produce at high titres, have a
      promiscuous host-range, and, because of their ability to infect nondividing
      cells, lend themselves to in vivo gene delivery. Such advantages have led to
      their widespread and successful use in preclinical studies of arthritis gene
      therapy. While adenoviral vectors are well suited to 'proof of principle'
      experiments in laboratory animals, there are several barriers to their use in
      human studies at this time. Transient transgene expression limits their
      application to strategies, such as synovial ablation, which do not require
      extended periods of gene expression. Moreover, there are strong immunological
      barriers to repeat dosing. In addition, safety concerns predicate local, rather
      than systemic, delivery of the virus. Continued engineering of the adenoviral
      genome is producing vectors with improved properties, which may eventually
      overcome these issues. Promising avenues include the development of 'gutted'
      vectors encoding no endogenous viral genes and of adenovirus-AAV chimeras.
      Whether these will offer advantages over existing vectors, which may already
      provide safe, long-term gene expression following in vivo delivery, remains to be
      seen.

PMID- 11299055
TI  - Angiogenesis in the pathogenesis of inflammatory joint and lung diseases.
AB  - This paper reviews hypotheses about roles of angiogenesis in the pathogenesis of
      inflammatory disease in two organs, the synovial joint and the lung.
      Neovascularisation is a fundamental process for growth and tissue repair after
      injury. Nevertheless, it may contribute to a variety of chronic inflammatory
      diseases, including rheumatoid arthritis, osteoarthritis, asthma, and pulmonary
      fibrosis. Inflammation can promote angiogenesis, and new vessels may enhance
      tissue inflammation. Angiogenesis in inflammatory disease may also contribute to
      tissue growth, disordered tissue perfusion, abnormal ossification, and enhanced
      responses to normal or pathological stimuli. Angiogenesis inhibitors may reduce
      inflammation and may also help to restore appropriate tissue structure and
      function.

PMID- 11299056
TI  - Genetic epidemiology. Giant cell arteritis and polymyalgia rheumatica.
AB  - Giant cell arteritis (GCA) (temporal arteritis) and polymyalgia rheumatica (PMR)
      are common, frequently related conditions in people generally over 50 years of
      age. Most studies have shown an association of GCA with HLA-DRB1 *04 alleles. As
      regards isolated PMR, however, the HLA class II genetic susceptibility varies
      from one population to another. Besides associations with HLA, tumor necrosis
      factor appears to influence susceptibility to both conditions. Genetic
      polymorphisms have also been considered to be important candidates as factors of
      susceptibility to GCA and PMR. In this regard, gene polymorphisms for ICAM-1
      (intercellular adhesion molecule 1), RANTES (regulated upon activation, normal T
      cell expressed, and presumably secreted), and interleukin (IL)-1 receptor
      antagonist seem to play a role in the pathogenesis of GCA and PMR in some
      populations. However, additional studies are required to clarify the genetic
      influence on susceptibility to these conditions.

PMID- 11299057
TI  - IL-17 derived from juxta-articular bone and synovium contributes to joint
      degradation in rheumatoid arthritis.
AB  - The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone
      destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex
      vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction,
      and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL
      17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA
      bone explants, IL-17 also increased bone resorption and decreased formation.
      Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of
      bone-derived endogenous IL-17 with specific inhibitors resulted in a protective
      inhibition of bone destruction. Conversely, intra-articular administration of IL
      17 into a normal mouse joint induced cartilage degradation. In conclusion, the
      contribution of IL-17 derived from synovium and bone marrow T cells to joint
      destruction suggests the control of IL-17 for the treatment of RA.

PMID- 11299058
TI  - Von Willebrand factor propeptide as a marker of disease activity in systemic
      sclerosis (scleroderma).
AB  - In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations
      of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but
      the propeptide showed less variability within patient subgroups. Higher values of
      the propeptide were observed in patients with early pulmonary involvement. A
      closer correlation of the propeptide than of vWf to biochemical markers of
      activity was also evident. Our results suggest that the propeptide, despite a
      shorter circulating half-time and lower plasma concentrations than vWf, is more
      useful in the assessment of disease activity in SSc.

PMID- 11299059
TI  - Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its
      relation to clinical variables in inflammatory arthritis.
AB  - Hypothalamic-pituitary-adrenal underactivity has been reported in rheumatoid
      arthritis (RA). This phenomenon has implications with regard to the pathogenesis
      and treatment of the disease. The present study was designed to evaluate the
      secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) and its
      relation to clinical variables in RA, spondyloarthropathy (Spa), and
      undifferentiated inflammatory arthritis (UIA). Eighty-seven patients (38 with RA,
      29 with Spa, and 20 with UIA) were studied, of whom 54 were women. Only 12
      patients (14%) had taken glucocorticoids previously. Age-matched, healthy women
      (134) and men (149) served as controls. Fasting blood samples were taken for
      determination of the erythrocyte sedimentation rate (ESR), serum DHEAS and
      insulin, and plasma glucose. Insulin resistance was estimated by the homeostasis
      model assessment (HOMAIR). DHEAS concentrations were significantly decreased in
      both women and men with inflammatory arthritis (IA) (P < 0.001). In 24 patients
      (28%), DHEAS levels were below the lower extreme ranges found for controls.
      Multiple intergroup comparisons revealed similarly decreased concentrations in
      each disease subset in both women and men. After the ESR, previous glucocorticoid
      usage, current treatment with nonsteroidal anti-inflammatory drugs, duration of
      disease and HOMAIR were controlled for, the differences in DHEAS levels between
      patients and controls were markedly attenuated in women (P = 0.050) and were no
      longer present in men (P = 0.133). We concluded that low DHEAS concentrations are
      commonly encountered in IA and, in women, this may not be fully explainable by
      disease-related parameters. The role of hypoadrenalism in the pathophysiology of
      IA deserves further elucidation. DHEA replacement may be indicated in many
      patients with IA, even in those not taking glucocorticoids.

PMID- 11299060
TI  - B lymphocyte involvement in ankylosing spondylitis: the heavy chain variable
      segment gene repertoire of B lymphocytes from germinal center-like foci in the
      synovial membrane indicates antigen selection.
AB  - The synovial membrane (SM) of affected joints in ankylosing spondylitis (AS) is
      infiltrated by germinal center-like aggregates (foci) of lymphocytes similar to
      rheumatoid arthritis (RA). We characterized the rearranged heavy chain variable
      segment (VH) genes in the SM for gene usage and the mutational pattern to
      elucidate the B lymphocyte involvement in AS. Cryosections from an AS-derived SM
      were stained for B and T lymphocytes. B cells were isolated from different areas
      of a focus. The rearranged VH genes were amplified by semi-nested polymerase
      chain reaction (PCR) using oligonucleotides specific for the six different VH
      families and heavy chain joining segments (JHs). PCR products were cloned and
      sequenced.Fifty-nine of 70 different heavy chain gene rearrangements were
      potentially functional. Most of the rearranged genes were mutated (range, 1-15%).
      Thirty of 70 products had a mutational pattern typical for antigen selection.
      Most of the rearranged VH genes belonged to the VH3 family (54%), consistent with
      data from healthy donors and patients with RA, while VH4 genes, in contrast to
      RA, were identified less frequently (10%) and VH5 genes were over-represented
      (11%). In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34
      were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used
      (11%). One VH1-derived and one VH3-derived B cell clone were expanded. CDR3 were
      shorter and more variable in length than in RA. Comparable with RA and reactive
      arthritis, there is a biased repertoire of selected VH genes, whereas the panel
      of represented genes is different and less clonal expansion was observed.

PMID- 11299061
TI  - Superantigen antagonist peptides.
AB  - The production of superantigenic exotoxins by Gram positive bacteria underlies
      the pathology of toxic shock syndrome. Future treatment strategies for
      superantigen-mediated diseases are likely to be directed at blocking the three
      way interaction between superantigen, T cell receptor and major
      histocompatibility class II molecule, which inititates an excessive and
      disordered inflammatory response. In this article, we review the first published
      data to address one such strategy in the context of other recognised and
      experimental treatments.

PMID- 11299062
TI  - Debate: transfusing to normal haemoglobin levels will not improve outcome.
AB  - Recent evidence suggests that critically ill patients are able to tolerate lower
      levels of haemoglobin than was previously believed. It is our goal to show that
      transfusing to a level of 100 g/l does not improve mortality and other clinically
      important outcomes in a critical care setting. Although many questions remain,
      many laboratory and clinical studies, including a recent randomized controlled
      trial (RCT), have established that transfusing to normal haemoglobin
      concentrations does not improve organ failure and mortality in the critically ill
      patient. In addition, a restrictive transfusion strategy will reduce exposure to
      allogeneic transfusions, result in more efficient use of red blood cells (RBCs),
      save blood overall, and decrease health care costs.

PMID- 11299063
TI  - Debate: Transfusing to normal hemoglobin levels improves outcome.
AB  - Red cells are uniquely designed to transport oxygen and facilitate oxygen uptake
      by systemic tissues. Blood transfusions are thus logical therapeutic choices in
      patients who exhibit signs of oxygen debt. A small number of studies that have
      addressed patients with metabolic or physiologic signs of oxygen debt or regional
      ischaemia suggest that liberal blood transfusion strategies improve outcome.
      Therefore, armed with an understanding of the variety of clinical presentations
      characterising oxygen debt, as well as an appreciation of the risks involved,
      blood transfusions should be considered in all critically ill patients. This
      includes the consideration of liberalized hemoglobin triggers and hemoglobin
      thresholds in normal ranges.

PMID- 11299065
TI  - Blending science and compassion: the 30th educational symposium of the Society of
      Critical Care Medicine, San Francisco, USA, 10-14 February 2001.

PMID- 11299064
TI  - Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in
      maintaining arterial oxygenation during acute respiratory failure.
AB  - Hypoxic pulmonary vasoconstriction continues to attract interest more than half a
      century after its original report because of persistent mystery about its
      biochemical mechanism and its exact physiological function. Recent work suggests
      an important role for pulmonary arteriolar smooth muscle cell oxygen-sensitive
      voltage-dependent potassium channels. Inhibition of these channels by decreased
      PO2 inhibits outward potassium current, causing membrane depolarization, and
      calcium entry through voltage-dependent calcium channels. Endothelium-derived
      vasoconstricting and vasodilating mediators modulate this intrinsic smooth muscle
      cell reactivity to hypoxia. However, refined modeling of hypoxic pulmonary
      vasoconstriction operating as a feedback mechanism in inhomogeneous lungs, using
      more realistic stimulus-response curves and confronted with direct measurements
      of regional blood flow distribution, shows a more effective than previously
      assessed ability of this remarkable intrapulmonary reflex to improve gas exchange
      and arterial oxygenation. Further studies could show clinical benefit of
      pharmacological manipulation of hypoxic pulmonary vasoconstriction, in
      circumstances of life-threatening hypoxemia.

PMID- 11299066
TI  - The acute effects of body position strategies and respiratory therapy in
      paralyzed patients with acute lung injury.
AB  - BACKGROUND: Routine turning of critically ill patients is a standard of care. In
      recent years, specialized beds that provide automated turning have been
      introduced. These beds have been reported to improve lung function, reduce
      hospital-acquired pneumonia, and facilitate secretion removal. This trial was
      designed to measure the physiological effects of routine turning and respiratory
      therapy in comparison with continuous lateral rotation (CLR). METHODS: The study
      was a prospective, quasi-experimental, random assignment, trial with patients
      serving as their own controls. Paralyzed, sedated patients with acute respiratory
      distress syndrome were eligible for study. Patients were randomized to receive
      four turning and secretion management regimens in random sequence for 6 h each
      over a period of 24 h: (1) routine turning every 2 h from the left to right
      lateral position; (2) routine turning every 2 h from the left to right lateral
      position including a 15-min period of manual percussion and postural drainage
      (P&PD); (3) CLR with a specialized bed that turned patients from left to right
      lateral position, pausing at each position for 2 min; and (4) CLR with a
      specialized bed that turned patients from left to right lateral position pausing
      at each position for 2 min, and a 15-min period of percussion provided by the
      pneumatic cushions of the bed every 2 h. RESULTS: Nineteen patients were entered
      into the study. There were no statistically significant differences in the
      measured cardiorespiratory variables. There was a tendency for the ratio of
      partial pressure of arterial oxygen to fractional inspired oxygen concentration
      (PaO2/FIO2) to increase (174 +/- 31 versus 188 +/- 36; P = 0.068) and for the
      ratio of deadspace to tidal volume (Vd/Vt) to decrease (0.62 +/- 0.18 versus 0.59
      +/- 0.18; P = 0.19) during periods of CLR, but these differences did not achieve
      statistical significance. There were statistically significant increases in
      sputum volume during the periods of CLR. The addition of P&PD did not increase
      sputum volume for the group as a whole. However, in the four patients producing
      more than 40 ml of sputum per day, P&PD increased sputum volume significantly.
      The number of patient turns increased from one every 2 h to one every 10 min
      during CLR. CONCLUSION: The acute effects of CLR are undoubtedly different in
      other patient populations (spinal cord injury and unilateral lung injury). The
      link between acute physiological changes and improved outcomes associated with
      CLR remain to be determined.

PMID- 11299067
TI  - Close relationship of tissue plasminogen activator-plasminogen activator
      inhibitor-1 complex with multiple organ dysfunction syndrome investigated by
      means of the artificial pancreas.
AB  - BACKGROUND: Glucose tolerance (GT) has not been taken into consideration in
      investigations concerning relationships between coagulopathy and multiple organ
      dysfunction syndrome (MODS), and endothelial cell activation/endothelial cell
      injury (ECA/ECI) in septic patients, although coagulopathy is known to be
      influenced by blood glucose level. We investigated those relationships under
      strict blood glucose control and evaluation of GT with the glucose clamp method
      by means of the artificial pancreas in nine septic patients with glucose
      intolerance. The relationships between GT and blood stress related hormone levels
      (SRH) were also investigated. METHODS: The amount of metabolized glucose (M
      value), as the parameter of GT, was measured by the euglycemic hyperinsulinemic
      glucose clamp method, in which the blood glucose level was clamped at 80 mg/dl
      under a continuous insulin infusion rate of 1.12 mU/kg per min, using the
      artificial pancreas, STG-22. Multiple organ failure (MOF) score was calculated
      using the MOF criteria of Japanese Association for Critical Care Medicine.
      Regarding coagulopathy, the following parameters were used: disseminated
      intravascular coagulation (DIC) score (calculated from the DIC criteria of the
      Ministry of Health and Welfare of Japan) and the parameters used for calculating
      DIC score, protein-C, protein-S, plasminogen, antithrombin III (AT-III),
      plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator-PAI-1
      (tPA-PAI-1) complex. Thrombomodulin (TM) was measured as the indicator of ECI.
      RESULTS: There were no significant correlations between M value and SRH,
      parameters indicating coagulopathy and the MOF score. The MOF score and blood TM
      levels were positively correlated with DIC score, thrombin-AT-III complex and tPA
      PAI-1 complex, and negatively correlated with blood platelet count. CONCLUSIONS:
      GT was not significantly related to SRH, coagulopathy and MODS under strict blood
      glucose control. Hypercoagulability was closely related to MODS and ECI. Among
      the parameters indicating coagulopathy, tPA-PAI-1 complex, which is considered to
      originate from ECA, seemed to be a sensitive parameter of MODS and ECI, and might
      be a predictive marker of MODS. The treatment for reducing hypercoagulability and
      ECA/ECI were thought to be justified as one of the therapies for acutely ill
      septic patients.

PMID- 11299068
TI  - Survival of patients transferred to tertiary intensive care from rural community
      hospitals.
AB  - BACKGROUND: Accessibility to tertiary intensive care resources differs among
      hospitals within a rural region. Determining whether accessibility is associated
      with outcome is important for understanding the role of regionalization when
      providing critical care to a rural population. METHODS: In a prospective design,
      we identified and recorded the mortality ratio, percentage of unanticipated
      deaths, length of stay in the intensive care unit (ICU), and survival time of 147
      patients transferred directly from other hospitals and 178 transferred from the
      wards within a rural tertiary-care hospital. RESULTS: The two groups did not
      differ significantly in the characteristics measured. Differences in access to
      tertiary critical care in this rural region did not affect survival or length of
      stay after admission to this tertiary ICU. The odds ratio (1.14; 95% confidence
      interval 0.72-1.83) for mortality associated with transfer from a rural community
      hospital was not statistically significant. CONCLUSIONS: Patients at community
      hospitals in this area who develop need for tertiary critical care are just as
      likely to survive as patients who develop ICU needs on the wards of this rural
      tertiary-care hospital, despite different accessibility to tertiary intensive
      care services.

PMID- 11299071
TI  - More on trans fatty acids.

PMID- 11299072
TI  - Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and
      related disorders.
AB  - The generation of reactive oxygen species (free radicals) is an important factor
      in the development and maintenance of rheumatoid arthritis in humans and animal
      models. One source of free radicals is nitric oxide produced within the
      synoviocytes and chondrocytes and giving rise to the highly toxic radical
      peroxynitrite. Several cytokines, including tumour necrosis factor-alpha
      (TNFalpha) are involved in the formation of free radicals, partly by increasing
      the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of
      the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines,
      steroids and methotrexate can suppress nitric oxide synthase. Dietary
      antioxidants include ascorbate and the tocopherols and beneficial effects of high
      doses have been reported especially in osteoarthritis. There is also evidence for
      beneficial effects of beta-carotene and selenium, the latter being a component of
      the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids
      (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid
      synthesis, and the n-6 group which can increase formation of the pro-inflammatory
      cytokines TNFalpha and interleukin-6, and of reactive oxygen species. Some
      prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often
      oppose the inflammatory effects of some n-6-PUFA. gamma-linolenic acid (GLA) is a
      precursor of prostaglandin E1, a fact which may account for its reported ability
      to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as
      eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis,
      possibly by suppression of the immune system and its cytokine repertoire. Some
      other oils of marine origin (e.g. from the green-lipped mussel) and a range of
      vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti
      inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a
      growing scientific rationale for the use of dietary supplements as adjuncts in
      the treatment of inflammatory disorders such as rheumatoid arthritis and
      osteoarthritis.

PMID- 11299073
TI  - A perspective on food energy standards for nutrition labelling.
AB  - Food energy values used for nutrition labelling and other purposes are
      traditionally based on the metabolisable energy (ME) standard, which has recent
      support from. By reference to current practices and published data, the present
      review critically examines the ME standard and support for it. Theoretical and
      experimental evidence on the validity of ME and alternatives are considered. ME
      and alternatives are applied to 1189 foods to assess outcomes. The potential
      impact of implementing a better standard in food labelling, documentation of
      energy requirements and food tables, and its impact on users including consumers,
      trade and professionals, are also examined. Since 1987 twenty-two expert reviews,
      reports and regulatory documents have fully or partly dropped the ME standard.
      The principal reason given is that ME only approximates energy supply by
      nutrients, particularly fermentable carbohydrates. ME has been replaced by net
      metabolisable energy (NME), which accounts for the efficiency of fuel utilisation
      in metabolism. Data collated from modern indirect calorimetry studies in human
      subjects show NME to be valid and applicable to each source of food energy, not
      just carbohydrates. NME is robust; two independent approaches give almost
      identical results (human calorimetry and calculation of free energy or net ATP
      yield) and these approaches are well supported by studies in animals. By
      contrast, the theoretical basis of ME is totally flawed. ME incompletely
      represents the energy balance equation, with substantial energy losses in a
      missing term. In using NME factors an account is made of frequent over
      approximations by the ME system, up to 25 % of the NME for individual foods among
      1189 foods in British tables, particularly low-energy-density traditional foods.
      A new simple general factor system is possible based on NME, yet the minimal
      experimental methodology is no more than that required for ME. By accounting for
      unavailable carbohydrate the new factor system appears as specific to foods as
      the USA's food-specific Atwater system, while it is more representative of energy
      supply from food components. The NME content of foods is readily calculable as
      the sum from fat (37 kJ/g), protein (13 kJ/g), available carbohydrate (16 kJ/g),
      fully-fermentable carbohydrate (8 kJ/g), alcohol (26 kJ/g) and other components.
      Obstacles to the implementation of NME appear to be subjective and minor. In
      conclusion, the ME standard is at best an approximate surrogate for NME, and
      inadequately approximates food energy values for the purpose of informing the
      consumer about the impact on energy balance of the energy supply for equal intake
      of individual foods. NME is superior to ME for nutrition labelling and other
      purposes.

PMID- 11299074
TI  - Influence of vitamin A status on the regulation of uridine (5'-)diphosphate
      glucuronosyltransferase (UGT) 1A1 and UGT1A6 expression by L-triiodothyronine.
AB  - The uridine (5'-)diphosphate-glucuronosyltransferases (UGT) are involved in the
      phase II of various xenobiotics and endogenous compounds. They are responsible
      for glucuronidation of many substrates, especially including bilirubin (UGT1A1)
      and phenolic compounds (UGT1A6). We previously showed that the expression of both
      isoforms is regulated at the transcriptional level by thyroid hormone in rat
      liver. In this present study, effects of vitamin A dietary intake (0, 1.72, 69
      microg retinol acetate/g food) on the regulation of UGT1A1 and UGT1A6 activity
      and expression by 3,5,3' triiodo-l-thyronine (l-T3) were examined in the same
      organ. Activities were determined toward bilirubin and 4-nitrophenol. UGT mRNA
      were analysed by reverse transcription and amplification methods (reverse
      transcription-polymerase chain reaction) and quantified by capillary
      electrophoresis. In rats fed a vitamin A-balanced diet, a single injection of l
      T3 (500 microg/kg body weight) increased UGT1A6 mRNA expression whereas this
      hormone decreased UGT1A1 mRNA expression. In addition we observed that the
      specific effect of l-T3 on UGT1A1 and UGT1A6 was reduced in animals receiving a
      vitamin A-enriched diet and disappeared in those fed a vitamin A-free diet. The
      modulations observed in mRNA expression are concomitant with those found for UGT
      activities. Our results demonstrate for the first time the existence of a strong
      interaction between vitamin A and thyroid hormone on the regulation of genes
      encoding cellular detoxification enzymes, in this case the UGT.

PMID- 11299075
TI  - Effects of photoperiod and feeding level on adipose tissue and muscle lipoprotein
      lipase activity and mRNA level in dry non-pregnant sheep.
AB  - The aim of the present study was to investigate the effects of photoperiod and
      feeding level on lipid metabolism in ovine perirenal and subcutaneous adipose
      tissues (AT) and in skeletal and cardiac muscles. Twenty dry non-pregnant
      ovariectomised ewes were divided into two groups and subjected to either 8 h or
      16 h light/d, and underfed at 22 % energy requirements for 7 d. Half of the ewes
      in each group were slaughtered and the remaining ewes were refed at 190 % energy
      requirements for 14 d, until slaughtering. Refeeding increased (2.6-4.3-fold)
      malic enzyme (ME), fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase
      (G6PDH) and glycerol-3-phosphate dehydrogenase (G3PDH) activities in subcutaneous
      AT as well as lipoprotein lipase (LPL) activity in perirenal (3.5-fold) and
      subcutaneous (10-fold) AT and to a lesser extent (1.4-fold) in the skeletal
      longissimus thoracis and cardiac muscles. Moreover, variations of LPL mRNA level
      followed variations of LPL activity: refeeding increased perirenal AT- and
      cardiac muscle-mRNA levels (7.4- and 2-fold respectively). The main finding of
      this study is that, for a given level of food intake, long days (compared with
      short days) increased the LPL activity in the longissimus thoracis muscle and, in
      refed ewes, the activities of LPL and ME in subcutaneous AT. Furthermore, long
      days increased LPL mRNA level in cardiac muscle and perirenal AT. Thus, our
      results show that there are direct effects of photoperiod on sheep AT lipogenic
      potential, as well as on muscle LPL activity, which are not caused by changes in
      nutrient availability.

PMID- 11299076
TI  - Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised
      rat.
AB  - The dose-dependent bone-sparing effects of dietary isoflavones (IF) were
      investigated in adult (7-month-old) Wistar rats. Forty animals were
      ovariectomised, allocated into four groups of ten rats each, and immediately
      treated orally with IF at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) microg/g
      body weight per d for 91 d; ten sham-operated (SH) controls received the same
      diet without added IF. Animals were killed on day 91. Both femoral failure load
      and total femoral, diaphyseal or metaphyseal bone mineral densities (BMD) were
      lower in OVX animals than in SH animals. Urinary deoxypyridinoline (DPD)
      excretion, a marker of bone resorption, and plasma osteocalcin (OC) levels, a
      marker of osteoblast activity, were higher in OVX animals than in SH animals.
      Total femoral and diaphyseal BMD and femoral failure load were similar in IF
      treated rats and SH rats. Although metaphyseal BMD in IF40 or IF80 rats was
      similar to that in SH rats, its value was lower in IF20 rats than in controls.
      The day 91 urinary DPD excretion in IF40 and IF80 rats, but not in IF20 rats, was
      similar to that in SH rats. Day 91 plasma OC concentrations in IF-treated rats
      were similar to day 45 values, but were decreased in OVX and SH rats. Thus, daily
      IF consumption prevented ovariectomy-induced bone loss, both by depressing bone
      resorption and stimulating osteoblast activity. Moreover, as only the highest IF
      level induced a weak uterotrophic activity, the optimal IF dose which preserves
      both cancellous and cortical bone, but exhibits no oestrogen-like effects on the
      uterus, was 40 microg/g body weight per d.

PMID- 11299078
TI  - Effects of an exogenous enzyme preparation on microbial protein synthesis, enzyme
      activity and attachment to feed in the Rumen Simulation Technique (Rusitec).
AB  - The effects of an exogenous enzyme preparation, the application method and feed
      type on ruminal fermentation and microbial protein synthesis were investigated
      using the rumen simulation technique (Rusitec). Steam-rolled barley grain and
      chopped alfalfa hay were sprayed with water (control, C), an enzyme preparation
      with a predominant xylanase activity (EF), or autoclaved enzyme (AEF) 24 h prior
      to feeding, or the enzyme was supplied in the buffer infused into the Rusitec
      (EI). Microbial N incorporation was measured using (15NH4)2SO4 in the buffer.
      Spent feed bags were pummelled mechanically in buffer to segregate the feed
      particle-associated (FPA) and feed particle-bound (FPB) bacterial fractions.
      Enzymes applied to feed reduced neutral-detergent fibre content, and increased
      the concentration of reducing sugars in barley grain, but not alfalfa hay.
      Ruminal cellulolytic bacteria were more numerous with EF than with C.
      Disappearance of DM from barley grain was higher with EF than with C, but alfalfa
      was unaffected by EF. Treatment EF increased incorporation of 15N into FPA and
      FPB fractions at 24 and 48 h. In contrast, AEF reduced the 24 h values, relative
      to C; AEF and C were similar at 48 h. Infused enzyme (EI) did not affect 15N
      incorporation. Xylanase activity in effluent was increased by EF and EI, compared
      to C, but not by AEF. Xylanase activity in FPA was higher at 48 h than at 24 h
      with all treatments; it was higher with EF than C at 24 and 48 h, but was not
      altered by AEF or EI. Applying enzymes onto feeds before feeding was more
      effective than dosing directly into the artificial rumen for increasing ruminal
      fibrolytic activity.

PMID- 11299077
TI  - Comparative gastrointestinal and plasma cholesterol responses of rats fed on
      cholesterol-free diets supplemented with guar gum and sodium alginate.
AB  - The present study investigated the digestion and cholesterol-lowering effects of
      the water-soluble NSP guar gum (GG) and sodium alginate (SA) in laboratory
      animals. Groups of five male Wistar strain rats were fed semi-purified
      cholesterol-free diets containing 0, 50 or 100 g NSP source/kg for 21 d which
      comprised a 14-d adaptation period followed by a 7-d balance period. Weight gain
      over the balance period and food conversion ratio decreased linearly with
      increasing NSP intake ( and respectively). DM digestibility decreased with
      increasing NSP intake and this effect was greater for SA-containing diets
      compared with GG-containing diets At the lower inclusion rate, 0.9-1.0 of the
      additional NSP was digested, but this value fell to 0.8 for both NSP sources at
      the 100 g/kg inclusion rate, implying that the capacity for near complete
      digestion of the test NSP had been exceeded. Intestinal tissue mass was increased
      in response to inclusion of both NSP sources. Caecal digesta pH decreased
      linearly with additional GG, but increased slightly with consumption of SA. Total
      caecal short-chain fatty acid concentrations (micromol/g caecal contents)
      increased markedly with 50 g GG/kg but did not increase further with 100 g GG/kg,
      and were slightly lower than control values in rats consuming SA. Plasma
      cholesterol concentration fell linearly with increasing NSP in the diet and the
      effect was similar for both GG and SA. Total output of faecal bile acids rose in
      rats fed 50 g GG/kg and 50 g SA/kg (59 micromol/7 d v. 24 micromol/7 d for
      control rats) with no further increase at the higher inclusion rate. These
      results show that SA has a strong hypocholesterolaemic effect in rats which is
      similar to that of GG, and that this effect is most likely to be mediated through
      an interruption in the entero-hepatic circulation of bile acids and not through
      increased hepatic supply of propionate from fermentation of the NSP in the large
      bowel.

PMID- 11299079
TI  - Dietary fat intake in healthy adolescents: inverse relationships between the
      estimated intake of saturated fatty acids and serum cholesterol.
AB  - The objective of the present study was to describe the intake of dietary fatty
      acids among healthy 15-year-old boys and girls and to relate the intake of
      specific fatty acids and the fatty acid composition of the serum cholesterol
      esters to serum lipid, apolipoprotein (Apo) and insulin concentrations
      respectively. Fifty-two girls and forty-two boys were randomly selected from the
      official population register. Unexpectedly, significant inverse associations were
      found between the dietary content of saturated fatty acids with a chain length of
      four to fifteen C atoms, mainly derived from milk fat, as well as the
      corresponding fatty acids in the serum cholesterol esters, on the one hand and
      the serum concentrations of cholesterol and ApoB on the other. The estimated
      dietary intake of 4:0-10:0, 12:0 and 14:0 respectively, were all significantly
      inversely related to the serum cholesterol (r -0.32, r -0.31, r -0.30, all and
      ApoB (r -0.42, r -0.42, and r -0.40, all concentrations in girls and 12:0 to the
      ApoB concentration (r -0.55, in boys. The proportions of 12:0 and 15:0 in the
      serum cholesterol esters were negatively correlated with the serum cholesterol
      concentrations in both girls (r -0.34, r -0.32, and boys (r -0.53, r -0.32, and
      with the ApoB concentrations among boys (r -0.61, r -0.43, It is conceivable that
      milk fat contains or is associated with some component in the diet, or some other
      characteristics of the food intake, which counterbalances the expected positive
      relationships between saturated fat intake and lipid levels.

PMID- 11299080
TI  - Changes in intragastric meal distribution are better predictors of gastric
      emptying rate in conscious pigs than are meal viscosity or dietary fibre
      concentration.
AB  - The effect of dietary fibre on the gastric emptying rate of solids is
      controversial. Similarly, the mechanisms by which it modulates food intake are
      partially unknown. Gastric emptying and proximal v. distal stomach filling were
      evaluated in triplicate on four conscious pigs using scintigraphic imaging. Each
      animal received in an isoenergetic manner a concentrate low-fibre diet enriched
      in starch (S) and two high-fibre diets based on sugar beet pulp (BP) or wheat
      bran (WB). All meals had the same viscosity before ingestion (100.0-100.5 Pa.s).
      Viscosity of the gastric contents was measured in four additional animals fitted
      with a gastric cannula. The gastric emptying rate of BP diet was significantly
      slower than S and WB diets (t1/2 78.4 (sem 5.68), 62.8 (sem 10.01) and 111.6 (sem
      10.82) min for S, WB and BP diets respectively, P<0.05). For BP diet only, rate
      of distal stomach filling was steady during the first 120 min after the meal
      whereas that of S and WB diets decreased in an exponential manner. Numerous
      backflow episodes from the distal into the proximal stomach were observed for BP
      diet that generated the larger intragastric viscosity (0.26 (sem 0.03), 0.3 (sem
      0.02) and 0.52 (sem 0.002) Pa.s for S, WB and BP respectively). In conclusion,
      viscosity of the meal or the percentage total fibre, unlike viscosity of the
      gastric contents, are poor predictors for emptying. The reduced emptying rate
      observed with BP is associated with major changes in intragastric distribution of
      the meal absent with WB and S diets.

PMID- 11299081
TI  - Analysis of energy density of food in relation to energy intake regulation in
      human subjects.
AB  - The relationship between energy density (ED) of food and drink consumption ad
      libitum and energy intake (EI) was analysed. EI was taken as average daily EI
      over the long term, and as EI during a single meal. Moreover, the distribution of
      EI over three ED categories was analysed. Average daily EI was related to ED of
      the food and drinks when ED was strongly influenced by specific macronutrients.
      When ED was strongly influenced by the weight of water, it was not related to EI.
      During a meal subjects monitored mainly weight, and to a lesser extent, the
      energy content of the food ingested. Therefore, covertly manipulated ED of a meal
      affected EI directly. The impact of ED on EI was modulated by dietary behaviours
      such as restraint. Overt manipulation of ED for 6 months showed that EI was
      adjusted to a decreased but not to an increased ED in dietary-unrestrained
      subjects, and that EI was adjusted to an increased but not to a decreased ED in
      dietary-restrained subjects. Knowledge of ED was shown to lead to an inverse
      relationship between portion sizes and ED during a meal. Average daily EI
      consisted of a distribution of EI over the three different categories of ED, so
      that obese women ate more of foods with a high ED and less of foods with a low ED
      compared with normal weight women (and nutritional guidelines). In conclusion, ED
      affected daily EI by means of macronutrient specific effects. EI from a meal with
      an unknown ED can become inversely related to EI through learning or
      conditioning. Therefore, the effect of ED on EI during a single meal observation
      cannot be extrapolated directly to the 24 h effect on EI. With regard to the
      treatment of obesity, a conscious decreased consumption of foods high in ED and
      an increase in consumption of low-ED food is necessary to decrease and
      subsequently maintain body weight, particularly in subjects with a sedentary
      lifestyle.

PMID- 11299082
TI  - Dietary patterns and their association with food and nutrient intake in the
      European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam
      study.
AB  - Dietary pattern analysis has recently received growing attention, as it might be
      more appropriate in studies of diet-disease associations than the single food or
      nutrient approach that has dominated past epidemiological research. Factor
      analysis is a technique which is commonly used to identify dietary patterns
      within study populations. However, the ability of factor solutions to account for
      variance of food and nutrient intake has so far remained unclear. The present
      study therefore explored the statistical properties of dietary patterns with
      regard to the explained variance. Food intake of 8975 men and 13 379 women,
      assessed by a food-frequency questionnaire, was aggregated into forty-seven
      separate food groups. Dietary patterns were identified by principal component
      analysis and subsequent varimax rotation. Seven factors were retained for both
      men and women, which accounted for about 31 % of the total variance. The
      explained variance was relatively high (>40 %) for cooked vegetables, sauce,
      meat, dessert, cake, bread other than wholemeal, raw vegetables, processed meat,
      high-fat cheese, butter and margarine. Factor scores were used to investigate
      associations between the factors and nutrient intake. The patterns accounted for
      relatively large proportions of variance of energy and macronutrient intake, but
      for less variance of alcohol and micronutrient intake, especially of retinol,
      beta-carotene, vitamin E, Ca and ascorbic acid. In addition, factors were related
      to age, BMI, physical activity, education, smoking and vitamin and mineral
      supplement use.

PMID- 11299083
TI  - Longitudinal trends in and tracking of energy and nutrient intake over 20 years
      in a Dutch cohort of men and women between 13 and 33 years of age: The Amsterdam
      growth and health longitudinal study.
AB  - The purpose of the present study was to describe the longitudinal development of
      nutrient intake and to determine the stability of this intake from adolescence
      into adulthood. Longitudinal data of the Amsterdam Growth and Health Longitudinal
      Study were analysed; the dietary intake of 200 subjects (males and females) was
      repeatedly measured (eight times) over a period of 20 years, covering the age
      period of 13-33 years. Dietary intake was determined with the detailed crosscheck
      dietary history interview. With use of multivariate ANOVA for repeated
      measurements, trends in macro- and micronutrients over time and differences
      between genders were analysed. Furthermore, stability coefficients, corrected for
      time-dependent (biological age) and time-independent covariates (gender) were
      calculated, taking into account all the measurements. The results showed
      significant time and gender effects for energy intake (kJ) and the following
      macronutrients: protein (g and % total energy supply), fat (g) and carbohydrate
      (g). Interaction effects between time and gender diminished when the
      macronutrients were calculated as a percentage of total energy intake. The
      micronutrients Ca, Fe and vitamins changed significantly over time and showed an
      interaction effect with gender, with the exception of cholesterol intake (mg/MJ),
      which did not show an interaction effect of time and gender. The tracking of the
      nutrient intake showed relatively low but significant stability coefficients for
      all macro- and micronutrients (0.28-0.52). In conclusion, dietary intake does
      change considerably over time, with the exception of polyunsaturated fat intake
      (% total energy supply) for both males and females and fat intake in females.
      Furthermore, stability coefficients for nutrients appeared to be low to moderate.
      Although these coefficients may be somewhat attenuated as a result of the
      relatively large measurement error of the dietary intake measurement, they
      suggest moderate stability of diet over time. These findings may imply that
      dietary intake is changeable and suggest that disease prevention measures can be
      implemented in adulthood.

PMID- 11299084
TI  - Dietary trans alpha-linolenic acid from deodorised rapeseed oil and plasma lipids
      and lipoproteins in healthy men: the TransLinE Study.
AB  - TRANS: isomers of alpha-linolenic acid, which are formed by deodorization of
      refined vegetable oils, can be found in significant amounts in edible oils.
      Effects of trans alpha-linolenic acid on plasma lipoproteins are unknown. We
      therefore investigated the effects of trans alpha-linolenic acid on plasma lipids
      and lipoproteins in healthy European men. Eighty-eight healthy men from three
      European countries (France, Scotland, UK and the Netherlands) first consumed for
      6 weeks a diet with experimental oils 'free' of trans fatty acids (run-in
      period). For the next 6 weeks, they were randomly allocated to a diet with
      experimental oils 'high' or 'low' in trans alpha-linolenic acid. Daily total
      trans alpha-linolenic acid intake in the high trans group was 1410 (range 583
      2642) mg. Experimental oils were provided as such, or incorporated into
      margarines, cheeses, muffins and biscuits. The high trans alpha-linolenic acid
      diet significantly increased the plasma LDL-:HDL-cholesterol ratio by 8.1 % (95 %
      CI 1.4, 15.3; and the total cholesterol:HDL-cholesterol ratio by 5.1 % (95 % CI
      0.4, 9.9; compared with the low-trans diet. This was largely explained by an
      increase in LDL-cholesterol on the high-trans diet, while no change was observed
      in the low-trans group (mean treatment effect of 4.7 % (95 % CI -0.8, 10.5; No
      effects were found on total cholesterol and HDL-cholesterol, triacylglycerols,
      apolipoprotein B and A-1, and lipoprotein(a) concentrations. In conclusion, trans
      alpha-linolenic acid may increase plasma LDL-:HDL-cholesterol and total
      cholesterol:HDL-cholesterol ratios. Whether diet-induced changes in these ratios
      truly affects the risk for CHD remains to be established.

PMID- 11299085
TI  - Cognitive performance and its relationship with postprandial metabolic changes
      after ingestion of different macronutrients in the morning.
AB  - The effect of carbohydrate, protein and fat ingestion on simple as well as
      complex cognitive functions and the relationship between the respective
      postprandial metabolic changes and changes in cognitive performance were studied
      in fifteen healthy male students. Subjects were tested in three sessions,
      separated by 1 week, for short-term changes in blood variables, indirect
      calorimetry, subjective performance and different objective performance tasks
      using a repeated-measures counterbalanced cross-over design. Measurements were
      made after an overnight fast before and hourly during 3 h after test meal
      ingestion. Test meals consisted of either pure carbohydrates, protein or fat and
      were served as isoenergetic (1670 kJ) spoonable creams with similar sensory
      properties. Most aspects of subjective performance did not differ between test
      meals. For all objective tasks, however, postprandial cognitive performance was
      best after fat ingestion concomitant with an almost constant glucose metabolism
      and constant metabolic activation state measured by glucagon:insulin (G:I). In
      contrast, carbohydrate as well as protein ingestion resulted in lower overall
      cognitive performance, both together with partly marked changes in glucose
      metabolism and metabolic activation. They also differently affected specific
      cognitive functions in relation to their specific effect on metabolism.
      Carbohydrate ingestion resulted in relatively better short-term memory and
      accuracy of tasks concomitant with low metabolic activation, whereas protein
      ingestion resulted in better attention and efficiency of tasks concomitant with
      higher metabolic activation. Our findings support the concept that good and
      stable cognitive performance is related to a balanced glucose metabolism and
      metabolic activation state.

PMID- 11299086
TI  - Exclusive breast-feeding is rarely practised in rural and urban Morogoro,
      Tanzania.
AB  - OBJECTIVE: To investigate and compare feeding practices among infants of less
      than 7 months of age in a rural and an urban area in Tanzania. DESIGN: Cross
      sectional, questionnaire-based interview of mothers and focus group discussions
      with extension workers and community leaders. SETTING: Eleven villages in a rural
      district and 10 wards in an urban district in the Morogoro region, Tanzania, west
      of Dar es Salaam. SUBJECTS: Probability samples of mothers with infants of less
      than 7 months of age from each area). RESULTS: Exclusive breast-feeding was
      rarely practised in either the rural or urban areas investigated. However, the
      urban mothers initiated breast-feeding earlier, discarded colostrum less
      frequently, breast-fed exclusively for a longer period, gave breast milk as the
      first feed more often and delayed the introduction of solid foods for longer than
      their rural counterparts. The rural mothers, on the other hand, breast-fed their
      previous infants slightly longer than the urban mothers. CONCLUSIONS: The better
      performance of urban mothers could be partly due to sustained breast-feeding
      support in hospital settings and other campaigns which may not have reached the
      rural areas. In both the rural and urban areas more efforts are needed to
      encourage exclusive breast-feeding, to avoid premature complementation and, in
      the case of the urban areas, to protect extended breast-feeding.

PMID- 11299087
TI  - Dietary inadequacies observed in homeless men visiting an emergency night shelter
      in Paris.
AB  - OBJECTIVE: To assess the dietary intake and the nutritional status of homeless
      men. SETTING: A night emergency shelter in Paris, France. DESIGN: Dietary survey
      (48-h) including alcohol intake and a questionnaire on age, duration of
      homelessness, smoking habits. Subjects were also weighed and measured. SUBJECTS:
      Ninety-seven men aged 18-72 years (mean 43.3), of whom 54% were homeless for more
      than 18 months, 82% were smokers and 53% were regular and/or excessive drinkers.
      RESULTS: The BMI distribution was shifted towards low values, the percentage of
      wasted persons being four times higher than in the reference population. The mean
      total energy intake was 2376 kcal and included a high and highly variable
      percentage of energy derived from alcohol (12.0% Among drinkers, the mean ethanol
      intake was 90 g and there was a significant negative correlation between ethanol
      and non-alcoholic energy intakes. The median intakes of potassium, calcium, zinc,
      vitamins B1, B2, and niacin were lower than European Population Reference Intakes
      but only the mean intake of vitamin B1 was significantly lower. Eighty percent of
      non-alcoholic energy was provided by charitable organisations. For most
      nutrients, the nutritional density of the shelter ration was not significantly
      different from the density of the foods purchased by the homeless. CONCLUSIONS:
      These data suggest that the content of some nutrients should be increased in
      existing food assistance programs for homeless people in France.

PMID- 11299088
TI  - An overview of the health status of migrants in France, in relation to their
      dietary practices.
AB  - OBJECTIVE: To review studies on the morbidity, mortality and nutrition of migrant
      populations in France. DESIGN: A systematic search of the bibliographic database
      Medline, and direct contact with associations and institutions concerned with
      migrants' health. RESULTS: In France, as in other host countries, migrants belong
      to the lowest socio-economic strata. They have on average better health and lower
      mortality than the local-born population. Health benefits are particularly
      noticeable in Mediterranean men, especially for affluence-related diseases such
      as cancer and cardiovascular diseases. North African men smoke as heavily as the
      local-born of the same occupational categories, and yet their mortality rates
      from lung cancer are notably lower. Such a paradox may be the result of a synergy
      between different phenomena such as the selection of the fittest applicants for
      immigration and the maintenance of healthy lifestyles from the countries of
      origin. In contrast, migrant women do not enjoy the same health advantages,
      possibly because they are less likely to be selected on the basis of their health
      and because they are often non-working. Adult migrants from southern Europe and
      North Africa report dietary practices consistent with the typical Mediterranean
      diet, which is renowned for its positive effects on health. CONCLUSIONS: The diet
      of Mediterranean adults living in France may partly explain the low rates of
      chronic diseases and high adult life expectancy observed in migrant men from
      northern Africa. Information about their diets might provide clues for the design
      of nutritional education campaigns aimed at low-income people.

PMID- 11299089
TI  - Diet profiles in a population sample from Mediterranean southern France.
AB  - OBJECTIVE: A Mediterranean diet quality index (MDQI) was devised to give an
      overall assessment of dietary habits and to identify groups at risk. DESIGN: The
      MDQI was based on scores given for selected levels of consumption of selected
      nutrients and foods. SETTING: Mediterranean southern France. SUBJECTS: The sample
      included 473 men and 491 women in three age classes recruited at random. RESULTS:
      Only 9.5% of men, 9.0% of women, 4.7% of 20-34 year old subjects, 6.6% of 35-54
      year old subjects and 14.0% of 55-76 year old subjects were shown to have a
      healthy diet. However, 10.1% of men, 8.6% of women, 19.4% of 20-34 year old
      subjects, 10.2% of 35-54 year old subjects and 4.6% of 55-76 year old subjects
      were shown to have a poor diet. There were significantly fewer smokers among
      subjects with a good diet but the distribution of moderate wine drinkers was
      comparable between those with a good diet and those with a poor diet.
      Correspondence analysis associated a healthy diet with 55-76 year old men and
      women living in rural areas, who had received primary schooling only and who were
      manual workers. Both men and women with a poor MDQI score tended to be young and
      smokers. In addition, women with a poor MDQI tended to be heavy drinkers and
      obese. CONCLUSIONS: This study showed that the Mediterranean model, which is
      generally recognized as a healthy diet, appears restricted to older people and to
      rural areas, whereas urbanized young people depart from it. A nutritional
      prevention policy targeted at young adults is required to encourage them to
      adhere to the Mediterranean model. Smoking and drinking showed different
      distribution patterns in the sample under study.

PMID- 11299090
TI  - Maternal cured meat consumption during pregnancy and risk of paediatric brain
      tumour in offspring: potentially harmful levels of intake.
AB  - OBJECTIVE: To describe the relationship between specific levels of nitrite intake
      from cured meat consumption during pregnancy and the relative risk of paediatric
      brain tumours in the offspring. DESIGN: Exposure data were previously collected
      for a population-based case-control study of paediatric brain tumours; data on
      nitrite content were obtained by a comprehensive literature review of surveys of
      residual nitrite content in cured meats published in the USA and Canada. The
      level of nitrite intake for each mother was predicted by year of pregnancy based
      on survey results. Dose-response was evaluated both categorically and
      continuously using polynomial and quadratic spline regression. SETTING: The US
      west coast: Los Angeles County, the San Francisco-Oakland Bay Area and the
      Seattle-Puget Sound area. SUBJECTS: There were 540 cases diagnosed between 1984
      and 1990 at ages varying from 0 to 19 years, and 801 controls frequency-matched
      by geographic area, age and birth year. RESULTS: In general, survey results
      suggest a trend of decreasing nitrite levels in cured meats over time. We
      observed a moderate increase in brain tumour risk in the offspring of mothers
      with relatively low levels of nitrite consumption from cured meats during
      pregnancy, and a two- to three-fold risk increase in offspring of mothers who
      consumed 3 mg day-1 nitrite from cured meats (about 125 g day-1 of cured meat
      consumption throughout the pregnancy). CONCLUSIONS: A substantial risk of
      paediatric brain tumour appears to be associated with relatively high levels of
      maternal cured meat consumption during pregnancy. A more scientifically valid
      approach than a literature review to estimate nitrite intake from cured meats and
      data from a large group of highly exposed subjects would be useful in determining
      potentially harmful levels.

PMID- 11299091
TI  - Dietary intake of soybean protein and menstrual cycle length in pre-menopausal
      Singapore Chinese women.
AB  - BACKGROUND: Intake of soybean protein was associated with a reduced risk of
      breast cancer in a case-control study. It has also been demonstrated to increase
      menstrual cycle length in an experimental setting. OBJECTIVE: To ascertain
      whether the association of soybean protein intakes with menstrual cycle length
      persists in an uncontrolled community setting. DESIGN: Cross-sectional food
      frequency dietary survey, menstrual cycle survey and prospective collection of
      menstrual cycle data. SETTING: A hospital clinic and a nursing college. SUBJECTS:
      Two hundred menstruating women. RESULTS: An association (P = 0.034) of higher
      intakes of soybean protein with increased menstrual cycle length, as recorded by
      self report and by prospectively recording three consecutive cycles, was
      observed. The risk of menstrual cycle length being greater than the median, when
      comparing the upper quartile (8.7-35.2 g x day(-1)) of soybean intake and the
      lowest quartile (0.1-3.3 g x day(-1)) was double, and this approached statistical
      significance (OR = 2.02, 95% CI = 0.88-4.64 and OR = 1.93, 95% CI = 0.82-4.56 for
      self-reported cycle length and cycle length as recorded by diary, respectively).
      In terms of the absolute association with cycle length, subjects in the upper
      quartile of soybean intake demonstrated a cycle length 1-2 days longer than did
      subjects in the lowest quartile. CONCLUSIONS: It is likely that the association
      between dietary intake of soybean protein and length of menstrual cycle prevails
      in the community setting. This is shown using both self-reported cycle length and
      cycle length as recorded in a prospective diary.

PMID- 11299092
TI  - The role of blood loss and diet in the aetiology of mild iron deficiency in
      premenopausal adult New Zealand women.
AB  - OBJECTIVE: To investigate the role of blood loss and diet in the aetiology of
      mild iron deficiency (MID) in premenopausal New Zealand women. Mild iron
      deficiency was defined as low, but not necessarily exhausted, iron stores (i.e.
      serum ferritin <20 microg/L) in the absence of anaemia (i.e. haemoglobin > or
      =120 g/L). DESIGN: Cross-sectional study of a volunteer sample of premenopausal
      adult women. Information on habitual dietary intakes (using a specially designed
      and validated computerised iron food frequency questionnaire), health and
      demographic status, sources of blood loss (including menstrual blood loss
      estimated using a validated menstrual recall method), contraceptive use, height
      and weight, haemoglobin, serum ferritin and C-reactive protein were collected.
      SETTING: Dunedin, New Zealand during 1996/1997. PARTICIPANTS: Three hundred and
      eighty-four women aged 18-40 years. RESULTS: The characteristics that were
      associated with an increased risk of MID were: low meat/fish/poultry intake, high
      menstrual blood loss, recent blood donation, nose bleeds, and low body mass
      index. The protective factors included shorter duration of menstrual bleeding,
      and multivitamin-mineral supplement use in the past year. CONCLUSIONS: There are
      a number of potentially modifiable factors that appear to influence risk of MID.
      Women with low menstrual blood loss may be able to decrease their risk of MID by
      increasing their meat/fish/poultry intake, while those with a higher menstrual
      blood loss may be able to decrease their risk by decreasing their menstrual blood
      loss, perhaps by changing their method of contraception. Women should be
      encouraged to maintain a healthy body weight, and those who choose to donate
      blood, or who experience nose bleeds, should have their iron stores monitored.

PMID- 11299093
TI  - Healthy eating in Ukraine: attitudes, barriers and information sources.
AB  - OBJECTIVE: To identify the major perceived influences on food choice, to examine
      the use of and trust in information sources concerning healthy eating, and to
      assess attitudes towards and barriers to adopting healthy eating practices in a
      post-USSR country (Ukraine). DESIGN: A survey of an urban adult population. The
      questions were adopted from the Pan-European Union (EU) Survey of Consumer
      Attitudes to Food, Nutrition and Health (1995-1996). SETTING: Lviv city, Ukraine.
      SUBJECTS: The survey included 296 adults (84 males, 212 females) aged 18-55
      years; they were primarily college students and subjects with tertiary education-
      the groups most likely to be both interested in healthy eating and affected by
      current socioeconomic downturns. RESULTS: The major factors in food choice were:
      'quality/freshness' (cited by 80%), 'price' (58%) and 'taste' (47%); only 34%
      cited 'trying to eat healthily'. More older people cited 'price' than
      'quality/freshness', and men were more likely than women to cite 'taste'. Sources
      of healthy eating information included: 'relatives/friends' (cited by 65%,
      trusted by 85%) and health professionals (trusted by 92%, but used by only 35%);
      while advertising was the least trusted source (cited by 28%). Fifty-three per
      cent of respondents considered their diet to be healthy enough without further
      changes; 50% thought of the nutritional aspects of the food they ate; fewer women
      than men considered their diet healthy, and more women than men thought about
      nutrition. Barriers to healthy eating included: 'cost' (cited by 65%), 'lack of
      time' (55%), 'self-control' (54%), 'selection influences' (41%), 'lack of
      knowledge' (32%), 'unpleasant foods' and 'resistance to change' (both 30%).
      CONCLUSIONS: Strategies to encourage healthy eating in this population should
      involve word-of-mouth nutrition education concerning low-cost healthy
      alternatives.

PMID- 11299095
TI  - What do users of reduced-fat dairy products know about the fat in their diets?
AB  - OBJECTIVES: To assess the fat intake and knowledge about the fat content of foods
      consumed by a sample of self reported users of reduced-fat dairy products.
      DESIGN: Cross-sectional study of a population-based sample of women shoppers.
      SETTING: A small, rural town (population approximately 6000) in central Victoria,
      Australia. SUBJECTS: Seventy-eight women aged 25-50 years, who regularly used at
      least one reduced-fat dairy product. RESULTS: Mean reported intake of total fat
      was lower while intake of dairy fat was similar to that of a national sample of
      women of the same age both in the whole sample and when under-reporters were
      excluded. The ability to identify major sources of fat in the diet as reported
      appeared to be limited. Less than half of the subjects were able to correctly
      estimate the fat content of reduced-fat dairy products relative to regular
      products and about one quarter of subjects reported replacing one kind of oil or
      fat with another as a strategy to reduce fat intake. Subjects were generally
      aware of the need to 'eat less fat' but few could articulate specific
      recommendations. A number of subjects reported using low fat diets to control
      their weight but few subjects appeared to understand the connection between fat
      intake and energy intake. CONCLUSIONS: The findings of this study raise important
      questions about how nutrition advice is understood and implemented by consumers,
      particularly the message to reduce fat intake and the role of energy balance in
      weight management. They also highlight the difficulty of interpreting information
      on food intake, in subjects who have modified their diet by reducing intake of
      specific foods.

PMID- 11299096
TI  - Comparison of two frequency questionnaires for quantifying fruit and vegetable
      intake.
AB  - OBJECTIVE: The effect on individual rankings and total intakes of nutrients of
      correcting total fruit and vegetable frequencies from a long food frequency
      questionnaire (FFQ) using the responses to two summary questions was examined in
      a group of women. METHODS: The performance of a self-administered FFQ in ranking
      individual levels of intake and estimating absolute levels of nutrient and energy
      intake was compared with the performance of the questionnaire when it was
      corrected for fruit and vegetable intake reported using the Block summary
      questions. SUBJECTS: The study population included 123 women, aged between 18 and
      54 years, who were recruited from the Family Planning Association Colposcopy
      Clinic in Sydney. RESULTS: Substantial and significant differences (P < 0.001)
      were found in fruit and vegetable intakes between the FFQ and the summary
      questions. Intake frequency by the FFQ was more than double that by the summary
      questions. When the FFQ was corrected for fruit and vegetable intakes using the
      summary questions, the intakes of beta-carotene, vitamins A and C, and dietary
      fibre were more than 20% lower (p < 0.001) than the uncorrected results. However,
      this had little effect on ranking individuals. This study also examined seasonal
      differences in vegetable intakes and differences in nutrient intakes when either
      summer or winter vegetable consumption was substituted for seasonal vegetable
      intake in the FFQ. Although there were seasonal differences for some foods, the
      substitution had little effect on intake of nutrients. CONCLUSION: These results
      indicate that important differences in intakes are observed when two methods,
      which appear to yield the same results, are used. Further work is needed to
      determine which, if either, of the two methods yields intakes that can be
      compared quantitatively with national references for assessing the adequacy of
      population intakes.

PMID- 11299094
TI  - Dietary beliefs in the Baltic republics.
AB  - OBJECTIVES: As beliefs and knowledge about the possible effects of foods on
      health can influence food behaviours, this study examined selected dietary
      beliefs in the Baltic countries and the association of beliefs related to salt
      intake and to types of fat with food behaviours. DESIGN: A cross-sectional study.
      SETTING: Data from three surveys conducted in Estonia, Latvia and Lithuania in
      the summer of 1997 were used to describe the prevalence of dietary beliefs in
      these countries and to investigate the association between beliefs and behaviours
      (using logistic regression). SUBJECTS: Representative national samples of adults
      were selected in each country (Estonia, n = 2018; Latvia, n = 2308; Lithuania, n
      = 2153). RESULTS: Misunderstood concepts (myths) related to dietary salt, types
      of fat, meat consumption and bread and potatoes were observed in high proportions
      of the population. Education level was an important correlate of beliefs related
      to salt intake and types of fat, people with a higher education level being more
      likely to be familiar with these issues. Correct beliefs were not consistently
      associated with healthier behaviours (e.g. less frequent use of salt at the table
      and use of non-animal fats for cooking), except for salt intake in Estonia.
      CONCLUSIONS: Several misunderstood dietary concepts (myths) are still prevalent
      in the Baltic countries. Correct beliefs related to salt intake and types of fat
      were not consistent predictors of healthier food behaviours. In-depth qualitative
      investigations are needed to better describe and understand dietary beliefs and
      attitudes in the Baltic countries, and to identify barriers to the adoption of
      healthy food habits.

PMID- 11299097
TI  - A household food inventory for North American Chinese.
AB  - OBJECTIVE: To determine whether a short set of questions about foods in the
      household can provide information about the fat-related dietary behaviour of
      individual household members in less-acculturated Chinese populations. DESIGN:
      Cross-sectional survey. PARTICIPANTS: The study population included 244 adult
      females of Chinese ethnicity in Seattle, WA, and Vancouver, BC, Canada. SETTING:
      Bilingual interviewers collected information on the presence of 14 high-fat foods
      and seven reduced-fat foods in the household. Respondents were also asked about
      the consumption of foods and behaviour reflective of adoption of Western dietary
      practices, fat-related dietary behaviour, changes in consumption of high-fat
      foods since immigration, and sociodemographic characteristics. RESULTS: Although
      this was a less-acculturated sample, many households had Western foods such as
      butter (58%), lunchmeats (36%), snack chips (43%), and 1% or skim milk (48%).
      Households with respondents who were younger, married, employed outside the home,
      and lived with young children had significantly more high-fat foods, while high
      education and longer percentage of life in North America were significantly
      associated with having more reduced-fat foods (P , or = 0.05). Participants
      living in households with more high-fat foods had higher-fat dietary behaviour
      than those with fewer high-fat foods (fat-related dietary behaviour score, 1.54
      versus 1.28; P < 0.001). Women in households with more reduced-fat foods had a
      significantly decreased consumption of high-fat foods since immigration compared
      with those in households with fewer reduced-fat foods (P < 0.001). Western
      dietary acculturation was higher among women in households both with more high
      fat foods and more reduced-fat food counterparts (P < or = 0.05). CONCLUSIONS:
      Our inventory of household foods was strongly associated with current dietary
      behaviour, changes in food consumption, and westernization of dietary patterns.
      This simple, practical measure may be a useful alternative dietary assessment
      tool in less-acculturated Chinese populations.

PMID- 11299098
TI  - PrimeScreen, a brief dietary screening tool: reproducibility and comparability
      with both a longer food frequency questionnaire and biomarkers.
AB  - OBJECTIVE: Diet is an important determinant of health outcomes, but physicians
      have few ways to identify persons with suboptimal diets. The purposes of this
      study were to examine the reproducibility of a short dietary assessment
      questionnaire (PrimeScreen) and to compare its results with those of a longer
      food frequency questionnaire and with plasma levels of selected nutrients.
      DESIGN: Each subject completed two PrimeScreen questionnaires at an interval of 2
      weeks and one full length, 131-item, semiquantitative food frequency
      questionnaire (SFFQ), and had a sample of blood drawn. We compared the
      PrimeScreen with two reference standards, the SFFQ and plasma levels of selected
      nutrients. SETTING: A large managed care organization in New England. SUBJECTS: A
      total of 160 men and women, aged 19-65 years, participated. RESULTS: For foods
      and food groups, the mean correlation coefficient (r) was 0.70 for
      reproducibility and 0.61 for comparability with the SFFQ. For nutrients, the mean
      r was 0.74 for reproducibility and 0.60 for comparability with the SFFQ. No
      substantial differences were evident by sex, race, body mass index, occupation or
      education. Correlation coefficients for the comparison of vitamin E, beta
      carotene and lutein/zeaxanthin intakes from the PrimeScreen with plasma levels
      were 0.33, 0.43 and 0.43, respectively. These values were similar to those
      comparing the SFFQ with plasma levels. The median time to complete PrimeScreen
      was 5 min; 87% of participants required fewer than 10 min. CONCLUSIONS: A quick
      way to assess quality of diet among adults, PrimeScreen has adequate
      reproducibility and its results compare well with a longer food frequency
      questionnaire and biomarkers.

PMID- 11299100
TI  - "I never go to bed with a girl on the first date, but that's more of a guideline
      than a rule"

PMID- 11299099
TI  - Agreement between a brief food frequency questionnaire and diet records using two
      statistical methods.
AB  - OBJECTIVE: To compare intra- and inter-method reliability of a semi-quantitative
      food frequency questionnaire (FFQ) designed specifically to measure beta carotene
      (BC) and retinol intake, using two methods - the limits of agreement (LOA) and
      the correlation coefficient. DESIGN: A cross-sectional study of dietary intake.
      SETTING: A randomized trial of vitamin A supplements in 2769 subjects with past
      asbestos exposure. SUBJECTS: Data from 57 men and 26 women, aged 28-72 years,
      living in Western Australia. METHODS: The FFQ was administered at baseline (FFQ1)
      and repeated 1 year later (FFQ2). Four 1-week diet records (DRs) were completed
      during the year. RESULTS: Mean agreement between FFQ2 and FFQ1 was 120% for BC
      and 98% for retinol. LOA were 47-306% and 21-459%, respectively. Mean agreement
      between FFQ2 and the DR was 149% for BC and 63% for retinol; LOA were 50-447% and
      11-349%, respectively. Mean agreement and LOA varied across energy intakes.
      Between the DR and FFQ2, correlation coefficients were 0.36 for BC and 0.51 for
      retinol. These varied considerably across age, gender and energy intakes and were
      not in accordance with limits of agreement findings. CONCLUSION: Although
      correlation coefficients were positive and significant, there was less than ideal
      intra-method and inter-method reliability shown by the limits of agreement
      method. Bias was uneven across the range of intakes, the LOA were wide and,
      compared with the DR, the FFQ significantly over-estimated BC and under-estimated
      retinol. This shows the limitations of calculating correlation coefficients
      alone, for assessing reliability and validity.

PMID- 11299101
TI  - Urinary tract infection associated with ureteral stents in renal transplantation.
AB  - OBJECTIVES: In the mid 1980s, ureteral stents were used in renal transplantation
      when ureteral injury had occurred. Subsequently, it was shown that routine
      ureteral stent placement at the time of transplantation reduced urological
      complications. We carried out a chart review on renal transplant patients and
      noted which patients developed urinary tract infections (UTIs) with stents in
      place, and whether these infections ultimately affected transplant outcome. We
      sought to distinguish subgroups of patients who were more likely to develop
      infection and to identify the optimum time for stent removal. PATIENTS AND
      METHODS: We performed a retrospective chart review of 213 patients who underwent
      renal transplantation in 1994 and 1995. Adequate follow-up information was
      available on 167 patients with intraoperative stent placement. Of these 167
      patients, 4 patients expired and 8 required transplant nephrectomy due to
      complications unrelated to the stent. RESULTS: In total, 35 patients (22.6%)
      developed a post-operative UTI. One infection occurred during the first week
      following transplant, 3 developed within 2 weeks, and importantly, the remaining
      32 infections occurred more than 2 weeks after transplant. An increase in
      infections in diabetics (25.7%) as compared to other transplant recipients
      (20.2%) was noted. Patients with cadaveric renal transplants are also at higher
      risk of UTI (24%) compared to those with living related donors (15%). CONCLUSION:
      The use of ureteral stents is safe, but is associated with a UTI rate of 22.6%.
      To reduce infection rates, we recommend stent removal within 14 days and earlier
      if possible, particularly in diabetic patients who have received a cadaveric
      renal transplant.

PMID- 11299102
TI  - Urinary tract infection associated with ureteral stents in renal transplantation.

PMID- 11299104
TI  - Feasibility of radiation and chemotherapy following cystectomy and orthotopic
      neobladder for invasive bladder cancer.

PMID- 11299103
TI  - Feasibility of radiation and chemotherapy following cystectomy and orthotopic
      neobladder for invasive bladder cancer.
AB  - Orthotopic neobladder has become the standard of care in the selected patient
      undergoing cystectomy for invasive bladder cancer. It satisfies all the criteria
      for an ideal urinary alternative without compromising the delivery of needed
      adjuvant therapy or treatment for recurrent disease. Forty patients underwent
      orthotopic neobladder formation. Five patients received full course adjuvant
      chemotherapy without change in the dose, schedule, type or timing of the protocol
      because of the neobladder. Three patients received full dose XRT to recurrent
      pelvic masses without compromising the neobladder function. Systemic chemotherapy
      was given to 8 patients as per standard protocol for metastatic disease with no
      changes due to the presence of the neobladder.

PMID- 11299106
TI  - Role of conservative surgery for invasive penile carcinoma.

PMID- 11299105
TI  - Role of conservative surgery for invasive penile carcinoma.
AB  - OBJECTIVES: Most penile tumors are suitable for standard partial or total penile
      amputation. We attempted to identify whether occasional patients with
      anatomically suitable penile carcinoma can be safely managed with unconventional
      techniques that preserve uninvolved penile structures. PATIENTS AND METHODS:
      Records of personal patients with anatomically suitable invasive penile carcinoma
      managed by unconventional surgical resections between 1979 and 1995 were
      reviewed. RESULTS: Fifteen patients who had conservative surgical resections were
      followed for 6-80 months. Eleven patients had no recurrence and were alive with
      no evidence of disease at 6-80 months (mean 45 months). Two patients developed 3
      local recurrences that were excised by further conservative resections and were
      alive with no evidence of disease at last follow up. One patient died of
      metastatic disease and 1 died of myocardial infarction. CONCLUSIONS: Variable
      preservation of function can be obtained while accomplishing acceptable survival
      and local control. We believe that these conservative surgical modalities for
      managing primary penile carcinoma warrant consideration in appropriately selected
      patients.

PMID- 11299107
TI  - Bacille Calmette-Guerin (BCG) associated epididymitis: a case report and review.
AB  - A case of Bacille Calmette-Guerin (BCG)-associated epididymitis that was non
      responsive to 6 months of antituberculous therapy, but stable after 2 years, is
      reported. We review the clinical and pathological features of previously reported
      cases of pathologically diagnosed BCG-associated epididymitis. Surgery has been
      the primary treatment for BCG-associated epididymitis in all previous cases.

PMID- 11299108
TI  - Urinary retention secondary to mullerian duct remnant in an infant.
AB  - To date only 2 cases of urinary retention secondary to a mullerian duct cyst have
      been reported in infancy. We report a third case of bladder outlet obstruction
      caused by massive dilatation of persistent mullerian remnant in a 2 month old
      boy, the youngest to date. Surgical intervention was done because patient
      continued to have retention following conservative management. The cyst was
      large, located in the midline, and was associated with an absent left kidney.

PMID- 11299109
TI  - Bilateral testicular microlithiasis: case report and review of the literature.
AB  - Testicular microlithiasis is a rare diagnostic entity of unknown etiology and
      clinical significance. We hereby describe a case of bilateral testicular
      microlithiasis in a 10 year-old boy with a past history of mumps. Diagnosis was
      made by ultrasonography. Serum testicular tumor markers (alpha fetoprotein and
      beta human chorionic gonadotropin) were negative. Although the clinical
      significance of testicular microlithiasis remains obscure, in view of its
      association with testicular tumor and other pathology, we advocate regular self
      examination and clinical follow-up with ultrasonography as an adjunct on a
      regular and long-term basis.

PMID- 11299110
TI  - Suction electrocautery device: an aid to decreasing localized air contamination.
AB  - Airborne contaminants have been documented as a source of contamination for
      operating room personnel. Although electrocautery and LASER evaporation of
      venereal warts have been proven to release into the immediate environment, human
      papilloma virus DNA,(1) actual shedding and infectivity of viral particles has
      not been demonstrated. Surgical masks do remove viral particles. The unanswered
      question is whether they are effective filters of larger volumes of contaminated
      operating room air. Devices have been reported to aid in removal of such
      particles from the working operative environment.(2) Some of these techniques
      require purchase of new and expensive equipment. We describe our technique for
      suction-assisted cautery, at no added cost compared with standard operative
      setup.

PMID- 11299111
TI  - EDITORIAL.

PMID- 11299112
TI  - Pathological T3 and/or margin positive prostate adenocarcinoma with undetectable
      postoperative PSA - to irradiate or not?: analysis of freedom from PSA failure.
AB  - We retrospectively analyzed 48 patients with pathological T3 (PT3) and/or margin
      positive disease who had undetectable or unknown postoperative serum prostate
      specific antigen (PSA) following radical prostatectomy. Twenty-nine patients
      received postoperative adjuvant radiotherapy (RT) while 19 did not. Follow-up
      ranged from 0.5 to 6.9 years with a median of 3.4 years for the irradiated group
      and 2.9 years for the surgery alone group. PSA outcome was available on all
      patients. Freedom from failure was defined as the maintenance of a serum PSA
      level of < 0.2 ng/ml and the absence of clinical local recurrence and distant
      metastasis. Actuarial overall survival was 92% for the entire group and showed no
      difference between the irradiated and non-irradiated groups. However, the 5-year
      actuarial disease free survival including freedom from PSA failure was
      statistically better in those treated with adjuvant RT than that in the surgery
      alone group (88% vs 46%, p=0.0035). The morbidity of adjuvant RT was acceptable
      with only 2 patients developing Grade 3 genitourinary complication.

PMID- 11299113
TI  - Alpha-blocker therapy for benign prostatic hyperplasia: a comparative review.
AB  - In the past decade there has been a shift in the primary approach to therapy for
      BPH, from surgical intervention to pharmacotherapy. Therapies with alpha
      blockers, particularly long-acting selective alpha1-adrenoreceptor antagonists,
      has proven effective, and hence has become a popular treatment option. In
      randomized controlled trials, 3 alpha-adrenoreceptor antagonists -terazosin,
      doxazosin, and tamsulosin -have been shown to significantly improve both the mean
      peak urinary flow and the severity of BPH-related symptoms. There are no
      currently published trials comparing the clinical efficacy of these drugs.
      Reports from non-comparative trials suggest that the effects on symptoms and flow
      rates are similar. However, side effects, such as postural hypotension, asthenia,
      and dizziness may be less with tamsulosin. Use of tamsulosin is associated with
      loss of ejaculation in 4.5% of men. Until differences in efficacy are
      demonstrated, the choice of alpha-blocker will depend on tolerance for side
      effects and convenience of administration.

PMID- 11299114
TI  - Scrotal cancer: deja vu.
AB  - Carcinoma of the scrotum is a rare disease. Two recent cases are briefly
      described and the condition reviewed from a historical perspective. Case 1: A 55
      year old man on minimal doses of immunosuppressives 10 years after renal
      transplantation developed 2 squamous cell carcinomas, one on the forehead, the
      other and larger was a 1.5 cm raised and thickened lesion of the scrotum. Both
      were excised, and a year later, he has had no recurrences; he continues his
      immunosuppressive-suppressive therapy. Case 2: A 38 year old man with an 8 year
      history of slowly progressing Acquired Immune Deficiency syndrome, presented with
      a 1 cm ulcerated slightly pigmented lesion of the scrotum. Excisional biopsy
      showed this to be Squamous cell carcinoma, not Kaposi's sarcoma as anticipated.
      He died of Aids, with no recurrence 9 months after excision.

PMID- 11299115
TI  - Post transurethral resection of prostate incontinence in previously radiated
      prostate cancer patients.
AB  - OBJECTIVES: This is a retrospective review evaluating the incidence of
      incontinence post transurethral resection of prostate (TURP) in patients who have
      had previous external beam radiation (XRT) for prostate cancer (PCA). MATERIALS
      AND METHODS: 1,230 patients underwent XRT for PCA between January 1985 and April
      1996. From this group, 16 patients mean age of 67.8 years (range 48-84) at the
      time of XRT had a subsequent TURP for obstructive symptoms a median of 3.25 years
      later (range 3 months to 10.2 years). Patients have been followed post TURP for a
      median of 5.0 months (range 1 to 81 months). RESULTS: Nineteen percent (3)
      patients developed incontinence post TURP. An additional patient remained in
      retention and continued to suffer overflow incontinence. Incontinence was
      associated with a shorter time interval between XRT and TURP (13 months versus
      55.3 months) and with a greater amount of prostatic resection (19 grams versus
      11.4 grams) when compared to the continent group, but did not meet statistical
      significance. CONCLUSION: A high risk of incontinence post TURP in previously
      radiated patients was demonstrated. The association with a shorter time interval
      between procedures and the larger resection suggests that a conservative approach
      is warranted. Studies with the use of preop and post TURP urodynamics would be
      useful in further defining risk factors in this population.

PMID- 11299116
TI  - Paratesticular tumor of Mullerian duct origin.
AB  - A 65 year old Caucasian male presented with a 4 year history of persistent right
      epididymal discomfort. There was no history of urinary tract infection, dysuria
      urethral discharge or trauma. Despite several courses of antibiotics and
      prolonged use of anti-inflammatory medications, his symptoms were unrelenting and
      had become unbearable. Past history revealed that he had undergone an
      uncomplicated transurethral prostatectomy for obstructive benign prostatic
      hyperplasia 6 years previously and a left inguinal herniorrhaphy 15 years ago.
      There was no history of estrogen use. Physical examination revealed a normal
      penis, penile urethra, urethral meatus, testes and left epididymis. There was
      induration of the right epididymis and the caput was exquisitely tender. Complete
      blood count and urinalysis were normal and urine culture was negative. A scrotal
      ultrasound failed to show any abnormality. The patient underwent scrotal
      exploration and a right epididymectomy. An incidental, soft, 2 cm mass was
      discovered within the spermatic cord adjacent to the superior aspect of the
      testicle and this was excised. Histologic examination of the epididymis was
      unremarkable and the other lesion was shown to be a cystic paratesticular
      mullerian tumor (Figure 1). The epididymalgia resolved post operatively and he
      has been asymptomatic with no evidence of recurrence for 4 years.

PMID- 11299117
TI  - Appendicovesical fistula: case report and review.
AB  - Appendicovesical fistulae are rare and occur secondary to acute or missed acute
      appendicitis. A 15 year old boy presented with urinary symptoms and a pelvic
      abscess on imaging studies. At laparotomy an appendicovesical fistula was
      encountered and was successfully managed by a right colectomy and ileal
      transverse colon anastomosis. The presentation and management of appendicovesical
      fistula is discussed.

PMID- 11299118
TI  - Critical review of the uroflowmetry.
AB  - Uroflowmetry is the measurement of a urinary flow rate by using the flow meter. A
      urine flow rate is the volume of urine (millilitres) expelled from the bladder
      via the urethra per unit of time (second). It is expressed in ml/s.(1) Urine flow
      curve is the plot of velocity of the voided urine against time. The urine stream
      is affected by voiding pressure (detrusor power) and bladder outlet resistance.
      Therefore, uroflowmetry evaluates the interaction of the urinary bladder
      expelling strength and bladder outlet resistance. This is the initial, non
      invasive urodynamic investigation for evaluation of patients with lower urinary
      tract symptoms (LUTS). Although, it is very simple and widely used urodynamic
      test, the results are nonspecific and required caution interpretations. In the
      next few pages we will review some aspects of this test, i.e. brief history,
      equipment, indications, procedure itself and interpretation of the results.

PMID- 11299119
TI  - Geographical patterns of allelic diversity in the Plasmodium falciparum malaria
      vaccine candidate, merozoite surface protein-2.
AB  - The polymorphic merozoite surface protein-2 (MSP-2) of Plasmodium falciparum is a
      major malaria-vaccine candidate. In the present study, PCR and hybridization with
      allelic-specific probes were used to type the Msp-2 gene from isolates from hypo
      endemic Brazil (N = 113), meso-endemic Vietnam (N = 208) and holo-endemic
      Tanzania (N = 67). The typing methods were designed to group isolates into the
      dimorphic allelic families FC27 and IC1 and to detect possible between-family
      recombination events. The analysis was complemented by a comparison of 156 Msp-2
      sequences from the GenBank database with 12 additional sequences obtained during
      the present study. Statistically significant differences were detected in pair
      wise comparisons of the distribution of Msp-2 allelic types in Brazil and
      Vietnam, and in Brazil and Tanzania, but not in Vietnam and Tanzania. The extent
      of allelic diversity in the Msp-2 gene, as estimated by the total number of
      different alleles found in a given parasite population and the mean multiplicity
      of infections, clearly paralleled the levels of malaria endemicity in the study
      areas. However, no correlation between age and multiplicity of infections was
      found in the subjects. The patterns of Msp-2 diversity in Brazil appeared to be
      temporally stable, since no significant difference was observed in the
      distribution of Msp-2 allelic types among isolates collected, 10--13 years apart,
      in the same area of Rondonia. Despite the extensive sequence diversity found in
      Msp-2 alleles, especially in the central repetitive region of the molecule,
      several instances of identical or nearly identical alleles were found among
      isolates from different countries and regions, possibly as a result of extensive
      homoplasy. No recombinant allele was detected by molecular typing in any of the
      study sites, and the GenBank database included only 12 recombinant sequences
      (representing 7% of all reported Msp-2 sequences), all of them with an IC1-type
      5' end and an FC27-type 3' end. A single, putative, crossover site was
      characterised for all recombinant alleles. Most of the allelic diversity observed
      was therefore attributable to variation in the repetitive region of the gene,
      instead of recombination between alleles of dimorphic families (as commonly
      found, for example, in the Msp-1 gene). The implications of these findings for
      studies on the genetic and antigenic diversity of malarial parasites are
      discussed.

PMID- 11299120
TI  - Low incidence of the severe complications of malaria and absence of malaria
      specific mortality, in Tensa, Sundergarh district, Orissa state, India, an area
      hyper-endemic for malaria.
AB  - The incidence of severe malaria and malaria-specific mortality were investigated
      in a hospital, for miners and their families, at Tensa in the Sundergarh district
      of Orissa state in India. Tensa lies in area where malaria (predominantly caused
      by Plasmodium falciparum) is hyper-endemic. The hospital records for 1995--1999
      showed that, although annual admissions for malaria increased over the study
      period, there were very few admissions for severe, complicated malaria and no
      reports of malaria-specific deaths. Most of the patients who had been admitted
      with cerebral malaria either came from areas around but not within the town of
      Tensa or were recent arrivals in the town. It appears that the outcome of malaria
      is influenced not only by the intensity of local transmission (which affects the
      immunological status of the human hosts) but also by social factors such as the
      education and health-seeking behaviour of the local population and the health
      care facilities available. The low incidence of severe malaria observed in Tensa
      was probably the result of patients presenting early in the course of their
      illness and taking antimalarial treatment, iron supplementation and supportive
      therapy at the appropriate times.

PMID- 11299121
TI  - The analysis of the cross-reactions occurring in antibody-ELISA for the detection
      of trypanosomes can improve identification of the parasite species involved.
AB  - In Africa, the main pathogenic trypanosomes of livestock are Trypanosoma vivax,
      T. congolense and T. brucei. The geographical distributions and hosts of these
      three species are very similar. As they differ markedly in pathogenicity and
      epidemiology, however, a species-specific serological test for infection would be
      very useful for epidemiological studies. The antibody-ELISA (Ab-ELISA) that have
      been developed for detecting the Trypanosoma spp. most commonly infecting
      livestock give satisfactory sensitivity and genus specificity. Unfortunately,
      they are not species-specific because of strong cross-reactions between the
      pathogenic Trypanosoma spp. In the present study, carried out in Burkina Faso,
      the results of standardized Ab-ELISA for T. vivax, T. brucei or T. congolense
      were compared using 1288 plasma samples from sheep experimentally infected with
      T. vivax, T. evansi and/or T. congolense. If the results were interpreted, as
      usual, only using a positivity threshold (PT), the strong cross-reactions
      observed led to a mean species-specificity of < 30%. However, analysis of the
      reactions observed in the three types of Ab-ELISA revealed that the homologous
      reactions were stronger than the heterologous for almost all of the single and
      mixed infections (98.3% and 99.0%, respectively). In monospecific infections
      exceeding the PT study of the positivity score produced in each of the three
      types of Ab-ELISA increased species-specificity to > 96%. It therefore appears
      that comparison of the strengths of the reactions seen in Ab-ELISA could greatly
      improve sero-epidemiological surveys of trypanosome infections in domestic
      ruminants, although the technique remains to be evaluated in experimentally
      infected cattle.

PMID- 11299122
TI  - Trypanosomatidae from wild mammals in the neotropical rainforest of French
      Guiana.
AB  - The initial filling of the reservoir behind the Petit Saut hydro-electric dam, on
      the Sinnamary River in French Guiana, threatened the terrestrial and arboreal
      animals living in the neotropical rainforest being flooded. During a rescue
      programme between 24 October and 12 November in 1994, many of these animals were
      checked for infection with trypanosomatids. Overall, 45 blood samples and 54 skin
      biopsies were collected from 53 mammals (of 13 species representing five orders)
      and blood samples were also taken from each of nine reptiles (six species from
      four families). When the skin biopsies and the buffy-coats from the blood samples
      were cultured in NNN medium, 10 of the cultures, each initiated with mammalian
      blood, were found to be positive for trypanosomatids. Multilocus enzyme
      electrophoresis (MLEE) on cellulose acetate plates, with 20 enzyme systems, was
      then used to investigate each of the positive cultures. The results were analysed
      by clustering from a genetic distance matrix, using the unweighted pair group
      method with arithmetic averages (UPGMA), and applying a bootstrap procedure to
      Wagner parsimony trees. A stock obtained from Didelphis marsupialis was
      identified as a zymodeme of Trypanosoma cruzi (Miles' zymodeme 1) known to cause
      Chagas disease in French Guiana. Five stocks (one each from Bradypus tridactylus,
      Tamandua tetradactyla and Alouatta seniculus and two from Saguinus midas) were of
      a single zymodeme close to Trypanosoma rangeli reference stock RGB. This is the
      first confirmation of the presence of Tr. rangeli in French Guiana, and the first
      time that it has been identified, by iso-enzyme analysis, in the neotropical
      primates A. seniculus and S. midas. Two other stocks, isolated from Choloepus
      didactylus, were related to Endotrypanum schaudinni reference stock LEM 2790.
      Although the remaining stocks, one from C. didactylus and the other from A.
      seniculus, clustered together on UPGMA and in a Wagner tree, they did not appear
      to be related to any of the reference stocks included in the UPGMA dendrogram.

PMID- 11299123
TI  - An epidemiological study of epilepsy and epileptic seizures in two rural
      Guatemalan communities.
AB  - A cross-sectional epidemiological study of two communities in Guatemala, El
      Jocote and Quesada, was conducted to determine the prevalence of epilepsy and
      epileptic seizures. An initial screening questionnaire was applied to detect
      individuals who had possibly suffered seizures in the past. These individuals
      were then examined more thoroughly by a neurologist, to confirm or reject them as
      cases of epilepsy. The crude prevalences of epilepsy so revealed were 28
      cases/1000 in El Jocote and 29 cases/1000 in Quesada. The prevalence of active
      epilepsy in each community was approximately 18 cases/thousand. The most common
      type of seizure suffered was of the generalised tonic--clonic type. Seventy-six
      of the individuals who had a history of epileptic seizures and 51 individuals
      from the same communities with no such history were then given brain scans, using
      computerized axial tomography. These neuro-imaging studies revealed some form of
      abnormal image in 33% (17) of the subjects with no history of seizures and 70%
      (53) of those with a history of seizures (chi(2) = 12.2; P < 0.00006). The
      frequency of detected brain abnormalities in the individuals who had suffered a
      single episode of seizures was similar to that in those who were classified as
      epileptic. The most commonly observed type of abnormality was punctate
      calcification, followed by cerebral oedema and hypodensities. The reasons for the
      high prevalences of epilepsy, epileptic seizures and abnormal neuro-images
      observed in the present study merit further investigation. Although
      neurocysticercosis caused by Taenia solium was thought to be a significant cause
      of the epilepsy occurring in the study communities, many apparently non-epileptic
      individuals have brain lesions indicative of this disease.

PMID- 11299124
TI  - Estimating the economic effects of cystic echinococcosis. Part 2: an endemic
      region in the United Kingdom, a wealthy, industrialized economy.
AB  - The economic costs of cystic echinococcosis (CE) in Wales, which is part of one
      of the most highly developed, industrialized countries in the World, were
      evaluated. In this region, the disease in both sheep and humans causes financial
      losses. The sheep-related costs in the most highly endemic area, of southern and
      mid Wales, were estimated from recently published prevalences of the disease in
      local sheep. No relevant and recent data were available on the sheep in the rest
      of Wales but these animals were assumed to have lower prevalences, in line with
      historical data, and were ignored in the economic analysis. The costs of the
      disease in humans were based on published incidences of human cases treated
      surgically and the costs of surgery as estimated from hospital records and by
      costing out the procedures each patient received whilst undergoing treatment. The
      quality of life of patients treated for CE was also determined and compared with
      that of healthy, case-matched controls, using a standard health-survey
      questionnaire (SF-36). The results indicated that the treated patients suffered
      some long-term morbidity, caused by the disease itself, its treatment or both.
      Although accurate monetary values were not calculated for this decreased quality
      of life, the results indicate that the economic effects of human CE are greater
      than simply the cost of treatment. Assuming that the long-term morbidity
      demonstrated does have an economic effect, each year CE in Wales is probably
      costing the U.K. economy more than U.S.$1 million, and perhaps as much as
      U.S.$7.9 million.

PMID- 11299125
TI  - Prevalence of infection with hepatitis C virus in Venezuela, as assessed with an
      immuno-assay based on synthetic peptides.
AB  - Information on infection with hepatitis C virus (HCV) in South America is scarce.
      The seroprevalences of antibodies to HCV among urban, rural and Amerindian
      populations from Venezuela, and the genotypes of the HCV isolates recovered, were
      therefore determined. A total of 2592 sera were tested with an immuno-assay which
      was developed in-house and based on synthetic peptides. Each reactive sample was
      then re-tested, using other enzyme immuno-assays and a reverse-transcription,
      nested PCR, and any sample confirmed positive (in any test) was considered HCV
      positive. Genotypes were determined by analysis of RFLP. Overall, 39 (1.5%) of
      the samples were found HCV positive. The results of the immuno-assays indicated
      that the seroprevalence of HCV markers among the Amerindians investigated
      (23/1082, or 2.1%) was significantly higher than that among the other subjects
      (16/1510, or 1.1%; P = 0.02). No such difference was observed in the numbers of
      subjects confirmed positive by PCR, however (6/1082 v. 10/1510), and some of the
      anti-HCV reactivity observed among Amerindians may have been the result of cross
      reactivity with parasitic infections. The relative low prevalence of active HCV
      infection (16/2582, or 0.6%) and the HCV genotypes observed (mainly genotype 1)
      are in agreement with the results of previous studies indicating that HCV is not
      autochthonous to South America. However, it is clear that the virus may now be
      found even in isolated Amerindian populations. The in-house, synthetic-peptide
      based immuno-assay seems to be a valuable tool for epidemiological studies.

PMID- 11299126
TI  - Seasonal and nocturnal landing/biting behaviour of Phlebotomus argentipes
      (Diptera: Psychodidae).
AB  - The nocturnal activity of Phlebotomus argentipes (Diptera: Psychodidae), the main
      vector of Leishmania donovani in India, was studied throughout a year, with
      monthly collections, between 18.00 and 06.00 hours, of the sandflies landing on
      15 humans and 15 cows in the village of Bahapur, Patna district. The cattle
      appeared to be better as bait, since more than five female P. argentipes were
      caught on them for each one caught on the human bait. Overall, although P.
      argentipes were caught during each collection hour from 18.00--06.00 hours, the
      numbers caught landing/biting peaked at 23.00--24.00 hours. There were, however,
      slight seasonal variations in the timing of this peak in activity. The numbers of
      P. argentipes caught/collection night also varied with season, being
      significantly higher during the summer than during the rainy season or winter (P
      < 0.01 for each), and apparently inversely correlated with rainfall. Male P.
      argentipes were caught in much higher numbers than the females of this species,
      with female:male ratios of 1:8 for the flies caught on human bait and of 1:13 for
      those collected from cattle. If the probability of a female P. argentipes being
      infected with L. donovani does not vary with season, peak transmission of this
      parasite to humans probably occurs between February and May, at the middle of
      night.

PMID- 11299127
TI  - Population genetics of the schistosome intermediate host Biomphalaria pfeifferi
      in the Zimbabwean highveld: implications for co-evolutionary theory.
AB  - Co-evolutionary theory proposes that polymorphisms in co-evolved traits may be
      maintained through differential selection in spatially heterogeneous
      environments. Spatial heterogeneity of the schistosome intermediate host,
      Biomphalaria pfeifferi, was investigated here, using RAPD markers. Overall, 256
      individuals, collected at 32 sites on 13 rivers in the Chiweshe region of
      Zimbabwe, were analysed. Significant genetic differentiation was demonstrated,
      both between populations from the different rivers and between populations
      collected at different sites on each of several of the rivers investigated.
      However, the presence of spatial differentiation between populations from
      individual rivers varied with river type. It was not apparent in permanent, deep,
      fast-flowing rivers, where high levels of migration, through passive dispersal
      along the rivers, are likely. The snails collected from shallow, semi-permanent
      rivers not only showed relatively high levels of population subdivision but also
      high levels of within-site genetic diversity, consistent with the existence of
      'co-evolutionary hot-spots' where schistosome infection may be prevalent. These
      results are discussed with reference to the population biology of B. pfeifferi
      and to host-parasite co-evolution.

PMID- 11299128
TI  - Brainstem dysfunction: another manifestation of post-malaria neurological
      syndrome?

PMID- 11299130
TI  - Neuropsychological functioning during the year following severe traumatic brain
      injury.
AB  - The neuropsychological functioning of a group of 65 adults with severe traumatic
      brain injury was assessed at 6 months and 1 year post-injury. The cognitive
      domains assessed were pre-morbid intellectual level, current level of general
      intellectual functioning, simple and complex attention, verbal memory, executive
      functioning, and perceptual functioning. At least 40%, and up to 74%, of the TBI
      patients displayed some degree of impairment on tests administered at 6 months.
      Improvement was found to occur in all areas of cognitive functioning over the
      first year following injury. Despite this improvement at least 31%, and up to
      63%, of TBI patients displayed some degree of impairment on tests administered at
      1 year post-injury. The various types of neuropsychological functioning were
      affected to different degrees, indicating that different aspects of cognition are
      more susceptible to injury, and that recovery takes place at a differential rate
      across functions. The implications of these findings for the appropriate planning
      and allocation of treatment and rehabilitation resources, and the development of
      effective rehabilitation interventions are outlined.

PMID- 11299131
TI  - Subjective symptomatology after traumatic head injury.
AB  - BACKGROUND: Controversy persists regarding the reasons for persistent subjective
      complaints after mild traumatic head injury (THI). STATEMENT OF PURPOSE: To
      evaluate the influence of injury severity, psychological factors, and financial
      contingencies on symptomatology after THI. METHODS: Subjective complaints about
      cognitive, emotional, and somatic symptoms, as assessed by a standardized self
      report inventory (Minnesota Multiphasic Personality Inventory-2; MMPI-2) were
      evaluated in 150 patients with THI. RESULTS: Individuals with mild THI
      demonstrated paradoxically greater symptomatology on the MMPI-2 than patients
      with moderate-to-severe THI. Furthermore, specific actuarial criteria for
      possible symptom magnification (Fake Bad Scale) were met about twice as often in
      patients with mild THI who were seeking financial compensation for alleged
      acquired dysfunction than in patients with mild THI without such external
      contingencies. CONCLUSION: The evaluation of persistent subjective complaints
      after THI should consider injury severity in concert with psychological and
      financial/motivational factors. Great caution should be taken in attributing
      persistent symptomatology after mild THI to cerebral dysfunction.

PMID- 11299132
TI  - Mobile phones as a new memory aid: a preliminary investigation using case
      studies.
AB  - Memory impairment is one of the most common concerns following a brain injury of
      any severity. The use of effective external memory aids can help minimize the
      devastating effects such memory impairment can have on an individual's everyday
      life. Reviewed in this report are case studies of five individuals suffering
      significant everyday memory problems that were given a new memory aid that
      utilizes standard mobile phones. Measurements included diary-format observations
      and qualitative feedback. The results of the study show promising outcomes for
      all of the cases, and have led to recent adaptations to allow for wider and more
      effective use of this memory aid.

PMID- 11299133
TI  - Sertraline to improve arousal and alertness in severe traumatic brain injury
      secondary to motor vehicle crashes.
AB  - OBJECTIVE: To establish whether or not the serotonin reuptake inhibitor (SSRI)
      sertraline can improve arousal and alertness of patients with traumatic brain
      injury (TBI) and associated diffuse axonal injury (DAI). Serotonin is a major
      inhibitory as well an excitatory neurotransmitter, and serotonergic neurons
      modulate the activity of brain regions responsible for motor control, arousal,
      attention, and emotional regulation. SETTING: Tertiary care inpatient
      rehabilitation centre directly attached to a university hospital level-one trauma
      centre. DESIGN: Prospective placebo-controlled randomized trial utilizing
      sertraline on admission to acute rehabilitation. DATA SET: Eleven subjects, post
      high speed motor vehicle crash and post-severe TBI (GCS < or = 8) with presumed
      DAI randomized to receive either sertraline 100mg per day or placebo for 2 weeks.
      All subjects were within 2 weeks of acute injury. Outcome measures recorded were
      the Orientation Log (daily), Agitated Behaviour Scale (daily), and the Galveston
      Orientation and Amnesia Test (weekly). RESULTS: Both placebo and active
      medication groups demonstrated similar rates of improvement on all three scales.
      There was no difference in the rates of recovery for either study group (p >
      0.05, ANOVA with repeated measures). The groups did not demonstrate a
      statistically significant negative effect on recovery either, although the size
      is too small for a statistically reliable beta-effect. CONCLUSION: This pilot
      study fails to establish whether the early use of sertraline may improve
      alertness, decrease agitation or improve cognitive recall of material. This may
      be due to the small size of the study group, the brief duration of treatment or
      by a skewed placebo group. Larger studies will be required to prove any efficacy.
      There were no complications with its use and sertraline did not demonstrate a
      detrimental effect on recovery. This indicates that sertraline may be safe to use
      in the treatment of psychiatric or behavioural complications attributable to TBI.

PMID- 11299134
TI  - Training brain injury rehabilitation therapists to use generalized teaching and
      interaction skills.
AB  - Persons sustaining a brain injury often exhibit aberrant response patterns and
      skill deficits that require remediation. To promote recovery, rehabilitation
      staff must be competent in use of therapeutic teaching and interaction skills.
      This study focused on teaching 13 direct-care rehabilitation therapists these
      skills in a multiple baseline design across skill dimensions. Performance-based
      approaches were used to promote acquisition of therapist skills, and the 'general
      case' strategy was used to enhance generalization. The general case approach
      involved use of multiple examples of teaching and interaction situations selected
      to sample the range of variability in the rehabilitation setting. Therapists were
      videotaped in simulations of various teaching and interaction situations before
      and after staff training. These observations were coded for correct use of
      teaching and interaction skills. Therapists demonstrated mean increases of
      approximately 30 percentage points in correct skill use after training. The
      present training format appears to provide an efficient strategy for training
      staff to promote rehabilitation efforts.

PMID- 11299135
TI  - Head injury and alexithymia: implications for family practice care.
AB  - BACKGROUND: Alexithymia, a deficit in emotional information processing, and a
      history of head injury have both been found to be related to high rates of
      psychosomatic illness, substance abuse, depression, and utilization of primary
      care services. To date, no study has examined the potential comorbidity of
      alexithymia and head injury in a family practice setting, a necessary step in
      evaluating the aetiologic role of head injury in the development of alexithymia.
      The goals of this study are to establish prevalence of head injury and
      alexithymia in a family practice setting and to evaluate the relation, if
      present, between the two. METHODS: Patients (n =135) of a family practice
      residency facility were screened using the Traumatic Brain Injury Questionnaire
      and the Toronto Alexithymia Scale-20. RESULTS: Forty-nine per cent of the
      participants reported a history of head injury and 18% were alexithymic. Those
      with a history of head injury had significantly higher scores of alexithymia. Chi
      square analysis indicated a relation between head injury and alexithymia.
      CONCLUSIONS: The high rates of self-reported history of head injury in family
      practice settings, particularly in the context of alexithymia, may adversely
      affect a physician's ability to care for these patients. Increasing physicians'
      awareness of head injury and the potential mediating role of alexithymia in
      medical and psychological illness may facilitate effective diagnosis and patient
      physician communication.

PMID- 11299136
TI  - Establishing minimum recommended standards for post-acute brain injury
      rehabilitation.
AB  - Brain injury is the biggest cause of disability for men under the age of 60 in
      the UK, and yet there are no nationally set minimum standards of care. This
      article describes the process undertaken by the South Thames Brain Injury
      Association (STBIRA) in setting out minimum standards for post-acute brain injury
      rehabilitation in inpatient facilities. These standards cover just one aspect of
      the patient's journey from coma to community. It is hoped that other groups will
      take up the challenge to set standards for other parts of the integrated care
      pathway, in order to ensure appropriate treatment for individuals with acquired
      brain injury.

PMID- 11299137
TI  - Altitudinal neglect in a patient with occipital infarction.
AB  - Visual neglect has been frequently described in a horizontal direction.
      Altitudinal neglect, however, has rarely been described and has been associated
      with bilateral lesions in the parieto-occipital or temporo-occipital region. The
      following case report presents a patient with marked altitudinal neglect of the
      inferior space which was elicited using a line bisection test. The previously
      healthy patient had well-defined lesions solely in the occipital cortex following
      an embolic infarction. The present case report underlines the possibility that
      bioccipital lesions themselves can be responsible for altitudinal neglect.

PMID- 11299138
TI  - Unilateral spatial neglect associated with chronic subdural haematoma: a case
      report.
AB  - A 69-year-old right-handed man who exhibited unilateral spatial neglect in
      association with a chronic subdural haematoma, presented with mild left arm and
      leg weakness first noted 4 weeks prior to admission. Neurologic examination on
      admission revealed a mild left hemiparesis, including the face. Neuropsychologic
      examination revealed left unilateral spatial neglect, but no language
      disturbance. Minimal support was necessary to maintain activities of daily
      living. Computed tomography revealed a large right temporoparietal, extraaxial
      hypodense fluid collection containing scattered hypodense foci. The haematoma was
      evacuated via a right parietal burr hole. Following surgery, the patient
      dramatically improved neurologically and neuropsychologically, as well as in
      independent performance of daily activities. It is suggested that the improvement
      in ADL provides a behavioural correlate of improvement in the latter, represented
      a behavioural correlate of improved cerebral function, and that either direct
      compression by the chronic subdural haematoma or an interhemispheric pressure
      difference had caused unilateral spatial neglect. Such neglect is an unusual
      consequence of chronic subdural haematoma.

PMID- 11299139
TI  - Dancing with a dream: the folly of pursuing alternative medicine.

PMID- 11299140
TI  - Preparing for the future: a 2020 vision for American health care.

PMID- 11299141
TI  - Enhancing the clinical research pipeline: training approaches for a new century.
AB  - There is growing concern that the numbers of physician-scientists being trained
      in U.S. academic health centers will not be sufficient to continue the rate of
      current progress in biomedical research. The authors believe that the needs of
      current trainees and junior faculty must be addressed immediately, and that
      programs to train the next generation of patient-oriented researchers must be
      established without delay. The authors describe a two-pronged approach to this
      looming crisis. First is a description of innovative educational programs
      implemented at one academic health center from the K-12 level through the medical
      school curriculum. Second, programs are discussed that have been developed to
      facilitate the recruitment, training, and retention of physician-scientists in
      the early parts of their professional careers. Four models of training
      "translational" investigators are presented, along with case studies of how these
      models have been implemented in real-life productive and professionally
      satisfying collaborations within one academic health center. The authors conclude
      by stating that to be prepared for the effects of future knowledge on human
      disease and preventive health, academic health centers must enhance training
      opportunities for physician-scientists.

PMID- 11299142
TI  - Marketplace reforms and primary care career decisions.
AB  - A dramatic shift in the postgraduate career choices of medical school graduates
      toward primary care occurred during the mid-1990s. While some attributed this
      shift to changes in medical school curricula, perceptions stemming from
      marketplace reforms were probably responsible. For the most part, these
      perceptions were probably generated through informal communications among medical
      students and through the media. More recently, additional marketplace influences,
      such as the consumer backlash toward managed care and unrealized gains in primary
      care physicians' personal incomes, may have fostered contrasting perceptions
      among medical students, leading to career choices away from primary care,
      particularly family practice. The authors offer two recommendations for enhancing
      the knowledge of medical students concerning workforce supply and career
      opportunities: an educational seminar in the second or third year of medical
      school, and a public-private partnership between the Bureau of Health Professions
      and the Association of American Medical Colleges to create a national database
      about the shape of the primary care and specialty workforces, accessible through
      the Internet for educators, students, and policymakers. The authors conclude that
      appropriate career counseling through these efficient methods could avoid future
      abrupt swings in specialty choices of medical school graduates and may facilitate
      a more predictable physician workforce supply.

PMID- 11299143
TI  - Implications of the hospitalist model for medical students' education.
AB  - At many academic health centers, medical students in internal medicine, family
      medicine, and pediatrics are working with a new form of attending physician, the
      hospitalist. Although a growing literature demonstrates the benefits of
      hospitalists for patients and housestaff, the influence of hospitalists on
      students has been underemphasized. Advantages of the hospitalist model for
      students can include hospitalists' expertise in general inpatient medicine, their
      availability to teach throughout the day, and their role-modeling of the
      provision of high-quality and efficient care. However, the change in the ward
      attending workforce from non-hospitalist generalists, subspecialists, and
      biomedical researchers to generalist-hospitalists potentially limits students'
      exposure to the broad range of career opportunities the former group represents.
      The authors propose a research agenda to investigate the educational impact of
      the hospitalist model, suggest strategies to mitigate the limitations in
      students' exposures to subspecialty faculty, and recommend professional
      development in teaching for hospitalists to ensure that student education thrives
      in this new environment of inpatient medicine.

PMID- 11299144
TI  - Implementation of a college-wide GME core curriculum.
AB  - As health care delivery and its associated costs have been scrutinized carefully
      over the past decade, educational institutions have been expected to demonstrate
      how a particular educational requirement such as residency training brings
      benefit to the purchasers and users of their health care services. As part of
      this trend, the Accreditation Council for Graduate Medical Education recently
      enacted new accreditation standards mandating the inclusion of curricular
      elements that expose residents to basic concepts and principles of the non
      technical areas of health care across a variety of topics, including ethics, cost
      containment, socioeconomics, medical-legal issues, communication skills, research
      design, statistics, and critical review of the medical literature. The authors
      report the efforts at the Medical University of South Carolina to overcome
      obstacles and successfully implement an institution-wide core curriculum program,
      dealing with the kinds of topics mentioned above, across 47 specialty and
      subspecialty programs with over 500 residents and fellows. The seminal events and
      critical strategies are described, along with lessons learned along the way. The
      following were key elements to success: (1) adhering to a strategic plan
      assigning oversight of residency education to the graduate medical education
      (GME) office; (2) gaining strong support from the dean and other college
      officials; (3) creating a stepwise centralization of residencies in college via
      the GME committee; (5) making the first core curriculum element one that had an
      excellent chance to succeed; (6) having core curriculum sessions begin in
      evenings and weekends to not interfere with regular curriculum, but later, when
      the value of the curriculum became evident to departments, moving the sessions to
      be within the week; (7) having the philosophy of the GME office be to maintain a
      flexible approach and serve departments.

PMID- 11299146
TI  - Rethinking the residency matching process and questioning the value of
      competition in medicine.

PMID- 11299145
TI  - Conflict resolution at the University of Ottawa Faculty of Medicine: The Pelican
      and the sign of the triangle.
AB  - In 1997 the University of Ottawa Medical School adopted a conflict-resolution
      policy for informally dealing with complaints of abuse, harassment and
      intimidation, sexual harassment, and scientific misconduct or misappropriation of
      intellectual property. In collaboration with the university's Faculty of Law,
      general conflict-resolution workshops were given for faculty and administration
      and mediation training was provided to medical faculty designated "complaint
      officers" under the policy. In this article, the authors describe the policy and
      training and then analyze the first major incident arising after the policy's
      implementation: the publication of disrespectful misogynist material in The
      Pelican, a medical student society newsletter. The Pelican incident is used as a
      "lessons learned" case study both in terms of its multiple outcomes and as an
      opportunity to pinpoint some important policy and practical considerations that
      emerged in implementing a conflict-resolution policy. The article also describes
      the results of a learning environment survey conducted after the Pelican
      incident.

PMID- 11299147
TI  - Putting a comprehensive violence curriculum on the fast track.

PMID- 11299151
TI  - The effect of medical education on primary care orientation: results of two
      national surveys of students' and residents' perspectives.
AB  - PURPOSE: To examine changes among a nationally representative sample of students
      and residents in their orientations toward primary care as reflected in their
      attitudes toward the psychosocial and technical aspects of medicine and their
      perceptions of the academic environment for primary care. METHOD: Confidential
      telephone interviews of stratified national probability samples of first- and
      fourth-year medical students and residents were conducted in 1994 and 1997. The
      1997 survey included 219 students and 241 residents who had also been interviewed
      in 1994. Participants were asked about their attitudes toward addressing
      psychosocial issues in medicine and their perceptions of faculty and peer
      attitudes toward primary care. Responses were compared over time and across
      groups. RESULTS: Between the first and fourth years of medical school, there was
      a decline over time in students' reported orientations to socioemotional aspects
      of patient care (61.6% versus 42.7%, p =.001) and their perceptions that working
      with psychosocial issues of patients made primary care more attractive (56.3%
      versus 43.5%, p =.01). This pattern continued for 1997 residents (PGY-3), who
      were even less likely to say that addressing psychosocial issues made primary
      care more attractive (26.9%). For fourth-year students in 1994 who became PGY-3
      residents in 1997, there was an increased perception that non-primary-care house
      officers and specialty faculty had positive attitudes toward primary care (20.8%
      versus 33.0%, p =.005; 28.3% versus 45.7%, p <.0001; respectively). CONCLUSIONS:
      Between 1994 and 1997 students and residents perceived a positive shift in the
      attitudes of peers and faculty toward primary care. During the course of their
      education and training, however, the students experienced an erosion of their
      orientations to primary care as they progressed through medical school into
      residency.

PMID- 11299153
TI  - A randomized trial of a problem-based learning approach for teaching
      epidemiology.
AB  - PURPOSE: To conduct a controlled trial of traditional and problem-based learning
      (PBL) methods of teaching epidemiology. METHOD: All second-year medical students
      (n = 136) at The University of Western Australia Medical School were offered the
      chance to participate in a randomized controlled trial of teaching methods for an
      epidemiology course. Students who consented to participate (n = 80) were randomly
      assigned to either a PBL or a traditional course. Students who did not consent or
      did not return the consent form (n = 56) were assigned to the traditional course.
      Students in both streams took identical quizzes and exams. These scores, a
      collection of semi-quantitative feedback from all students, and a qualitative
      analysis of interviews with a convenience sample of six students from each stream
      were compared. RESULTS: There was no significant difference in performances on
      quizzes or exams between PBL and traditional students. Students using PBL
      reported a stronger grasp of epidemiologic principles, enjoyed working with a
      group, and, at the end of the course, were more enthusiastic about epidemiology
      and its professional relevance to them than were students in the traditional
      course. PBL students worked more steadily during the semester but spent only
      marginally more time on the epidemiology course overall. Interviews corroborated
      these findings. Non-consenting students were older (p < 0.02) and more likely to
      come from non-English-speaking backgrounds (p < 0.005). CONCLUSIONS: PBL provides
      an academically equivalent but personally far richer learning experience. The
      adoption of PBL approaches to medical education makes it important to study
      whether PBL presents particular challenges for students whose first language is
      not the language of instruction.

PMID- 11299152
TI  - Fellowship training and career outcomes for primary care physician-faculty.
AB  - PURPOSE: To examine associations between fellowship training and career outcomes
      among primary care physician-faculty. METHOD: A total of 821 full-time primary
      care physician-faculty from 24 representative U.S. medical schools were surveyed
      using a self-administered questionnaire. Primary outcomes were recent grant
      submissions and funding, career referred publications, rank, and salary. Findings
      were adjusted for demographic and professional characteristics. RESULTS: Of the
      500 respondents, 234 of the physician-faculty had completed a fellowship and 266
      had not. Fellowship-trained physician-faculty were more than four times as likely
      to have submitted a grant proposal and to have had a grant funded (both p <
      0.0001) than were physician-faculty without fellowship training. They were also
      more likely to have had any refereed publications (OR 3.8, p < 0.0001) and to
      have achieved senior academic rank (OR = 1.9, p = 0.02). Among those with
      fellowship experience, the amount of research training was important. Those with
      at least one year of research experience in their fellowship program had more
      grant proposal submissions (OR = 1.9, p = 0.02), more grants funded (OR = 2.9, p
      = 0.0003), more publications (OR = 2.4, p = 0.02), and higher academic ranks (OR
      2.3, p = 0.03) than did those with less research training. Salaries were similar
      in every comparison. CONCLUSION: Fellowship-trained primary care physician
      faculty were more productive researchers and were more likely to have achieved
      senior academic rank than were their no-fellowship-trained peers. Even among
      physician-faculty with fellowship experience, more research training was
      associated with higher productivity and rank. Salaries were not affected by
      training experience.

PMID- 11299154
TI  - When do medical students identify career-influencing physician role models?
AB  - PURPOSE: To identify when medical students gain physician role models relative to
      when they make their specialty choices. METHOD: The 1998 graduating class of one
      medical school was surveyed about when and where they had made contact with their
      role models and whether they had made contact before or after making their
      specialty choices. Students also provided data about their demographics,
      curriculum pathways (problem-based or traditional), and specialty choices at
      matriculation and graduation. RESULTS: Of the 89 graduating seniors who responded
      (62%), 21 had role models they had known prior to matriculation, 51 had
      encountered their role models in medical school, and 51 had met their role models
      before making their specialty choices. Of the 51 students who had encountered
      their role models in medical school, 33 (65%) had done so before making their
      specialty choices. The mean time from matriculation to meeting a role model was
      24.9 +/- 11.6 months, and students on the problem-based learning pathway had met
      their role models earlier than had students on the traditional pathway.
      CONCLUSIONS: Most medical students have physician role models at graduation, and
      many of these students identify their physician role models at a point when the
      interactions can influence their specialty choices.

PMID- 11299155
TI  - Physical diagnosis findings among persons applying to work as standardized
      patients.
AB  - Sixty-six applicants for work as standardized patients (SPs) at a clinical skills
      assessment program underwent a physical examination. Murmurs, wheezes,
      hypertension, and goiter were found, which, if unaccounted for, could have
      influenced examinees' performances and diagnostic thinking.

PMID- 11299156
TI  - Effect of training location on students' clinical skills.
AB  - The clinical skills of second-year medical students trained in a hospital-based
      setting were compared with those of students trained in a community setting using
      an objective structured clinical exam. No statistically significant difference
      was found.

PMID- 11299157
TI  - Mechanistic case diagramming: a tool for problem-based learning.
AB  - Without appropriate learning tools to guide the application of knowledge to
      clinical situations, medical students in a problem-based learning (PBL)
      curriculum may revert to traditional modes of learning and hence deprive
      themselves of PBL's educational benefits. The author describes a technique
      involving the stepwise diagramming of pathophysiologic mechanisms leading from
      underlying causes to the symptoms and findings presented in a PBL case. This
      technique can guide clinical reasoning during an initial problem encounter, the
      identification of pertinent learning issues, and the subsequent integration of
      knowledge as relevant to the patient's case. The author suggests that training
      students and tutors to use this technique may allow the former to fully realize
      the benefits of PBL, including the ability to organize information for use in
      clinical contexts and the ability to critically reflect upon their own learning.

PMID- 11299158
TI  - Essential elements of communication in medical encounters: the Kalamazoo
      consensus statement.
AB  - In May 1999, 21 leaders and representatives from major medical education and
      professional organizations attended an invitational conference jointly sponsored
      by the Bayer Institute for Health Care Communication and the Fetzer INSTITUTE:
      The participants focused on delineating a coherent set of essential elements in
      physician-patient communication to: (1) facilitate the development,
      implementation, and evaluation of communication-oriented curricula in medical
      education and (2) inform the development of specific standards in this domain.
      Since the group included architects and representatives of five currently used
      models of doctor-patient communication, participants agreed that the goals might
      best be achieved through review and synthesis of the models. Presentations about
      the five models encompassed their research base, overarching views of the medical
      encounter, and current applications. All attendees participated in discussion of
      the models and common elements. Written proceedings generated during the
      conference were posted on an electronic listserv for review and comment by the
      entire group. A three-person writing committee synthesized suggestions, resolved
      questions, and posted a succession of drafts on a listserv. The current document
      was circulated to the entire group for final approval before it was submitted for
      publication. The group identified seven essential sets of communication tasks:
      (1) build the doctor-patient relationship; (2) open the discussion; (3) gather
      information; (4) understand the patient's perspective; (5) share information; (6)
      reach agreement on problems and plans; and (7) provide closure. These broadly
      supported elements provide a useful framework for communication-oriented
      curricula and standards.

PMID- 11299159
TI  - Using a WWW-based module for problem-based learning in a cardiovascular
      pharmacology course.
AB  - The authors have constructed a problem-based learning (PBL) computer program that
      makes full use of Internet facilities, and is aimed at providing a stimulating
      supplement to standard teaching practices. The authors report on students'
      reactions to this new method of teaching.

PMID- 11299161
TI  - The Interdisciplinary Generalist Curriculum Project.

PMID- 11299160
TI  - Using simulated patients in education about alcohol misuse.
AB  - It is important to educate medical students about alcohol misuse, but this
      process is hampered by negative attitudes and the unavailability of typical
      patients. However, simulated patients can describe full longitudinal histories in
      a characteristically defensive style and can provide direct feedback to student
      interviewers.

PMID- 11299162
TI  - With conviction, commitment, and creativity: promoting generalism and the
      preparation of the generalist physician.

PMID- 11299164
TI  - The Interdisciplinary Generalist Curriculum (IGC) project: an overview of its
      experience and outcomes.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project was a competitive,
      seven-year demonstration project funded by the Health Resources and Services
      Administration (HRSA). It was established to determine whether specific
      interdisciplinary innovations in preclinical medical school curricula could
      affect students' selection of careers in family medicine, general internal
      medicine, or general pediatrics. Through collaboration among the three generalist
      disciplines, the IGC innovation exposed all preclinical students in ten
      demonstration schools to a new or significantly enhanced preclinical curriculum
      that included a direct supervised clinical experience with a generalist physician
      preceptor. The project was managed by an interdisciplinary executive committee
      that was codirected by one representative each from family medicine, general
      internal medicine, and general pediatrics. A national advisory committee with
      representation from the academic and professional organizations of family
      medicine, internal medicine, pediatrics, and osteopathy provided input to the
      executive committee in guiding the project. The project was externally evaluated.
      Major outcomes of the IGC Project include sustained curricular changes in ten
      institutions, prompted by relatively few dollars and demonstration of models for
      collaboration at institutional and national levels. This supplement describes the
      IGC Project's experience and outcomes so that others may draw pertinent
      information to apply to their own efforts in medical education.

PMID- 11299165
TI  - From the primary care organizations consortium's proposal to the
      Interdisciplinary Generalist Curriculum Project.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project was one element of an
      overall federal government strategy designed to promote primary care education.
      This project, undertaken by the Division of Medicine and Dentistry (DMD), Bureau
      of Health Professions, Health Resources and Services Administration, U.S.
      Department of Health and Human Services, was the first large-scale medical
      education contract initiated by DMD. The IGC Project was based on a model
      proposed by the Primary Care Organizations Consortium (PCOC). The PCOC thesis was
      that "if students are to decide to pursue a generalist career they must have the
      opportunity to be taught by generalists." The PCOC Program required an explicit
      curriculum focusing on generalist knowledge and skills with an emphasis on
      technology, in the context of education that required training in ambulatory
      office-based settings. The PCOC Program specified that responsibility for the
      program's planning, implementation, and evaluation be shared by the three
      generalist physician faculties of family medicine, general internal medicine, and
      general pediatrics. In implementation of this demonstration project in ten
      medical schools across the nation, several lessons have been learned relative to
      enhancement of generalist education. Among these lessons is that seed money
      targeted to initiate modest change can act as a catalyst and improve the
      knowledge and skills afforded medical students concerning generalist practice.
      Limited funds provided over a sufficient period of time can induce schools to
      undertake significant curricular change.

PMID- 11299166
TI  - Implementation of the Interdisciplinary Generalist Curriculum Project:
      considerations of structure, funding, and design.
AB  - Implementation of the Interdisciplinary Generalist Curriculum (IGC) Project
      involved complex processes that reflect structural, funding, and intervention
      design considerations. Among structural considerations, the IGC Project benefited
      from a national structure above the level of the demonstration schools.
      Governance by committee was highly effective because it harnessed and balanced
      power. At the national level, governance by committee was enhanced by strong
      central coordination, and it had a role-modeling effect for governance at the
      school level. The IGC experience over the seven-year course of the project
      suggests that it is important to revisit the role of a national advisory
      committee over time and to revise that role as warranted. Funding considerations,
      including the importance of funding evaluation for a period of time long enough
      to measure intended impacts and the length and amount of funding to demonstration
      schools, are discussed. Prescription of the IGC intervention and the focus on
      years one and two of medical education are critical design considerations. The
      authors conclude that the IGC Project used relatively few federal dollars to
      demonstrate a highly prescribed intervention in a limited number of medical
      schools toward a clear and limited goal. IGC lessons apply to programs
      specifically targeting primary care education, but also to other medical school
      curricular innovations, and perhaps, to a larger framework of multi-site
      educational interventions.

PMID- 11299167
TI  - How did we make the Interdisciplinary Generalist Curriculum Project work?
      National efforts to facilitate success.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project created curricular
      changes at the participating schools with very little direct financial support. A
      reconsideration of the process of this national effort reveals many intangible
      elements that were as critical to the project's successes as were the direct
      dollars. Those factors included careful attention to the criteria for school
      selection, specific project requirements that allowed institutional flexibility
      in project evolution, national assistance in program implementation, early and
      ongoing national recognition for project schools, and a highly organized,
      involved, and goal-oriented national organization. This national initiative
      provides a successful model for future funding of projects in this era of
      dwindling financial support for medical education innovation.

PMID- 11299168
TI  - How did we make the Interdisciplinary Generalist Curriculum Project work? School
      level efforts to facilitate success.
AB  - This article examines how the schools funded by the Interdisciplinary Generalist
      Curriculum (IGC) Project handled the process of planning and implementing their
      proposals; incorporated the IGC requirements as templates for changes in
      educational programs and organizational infrastructures; and identified key
      educational and management issues that emerged over time. How collaboration
      flourished at each IGC school was the central functional ingredient for
      successful implementation. Shared power and support from the dean were essential
      for success. The need for excellent channels of communication among all
      constituencies in the process of curricular change cannot be overemphasized. The
      most common approach was the addition of the new interdisciplinary clinical
      curriculum to the existing, usually discipline-based, curriculum, with attempts
      to establish integrative horizontal connections among concurrent courses in years
      one and two. The integration, sequencing, and correlating of basic science and
      clinical material occupied much of the IGC course directors' time in the early
      stages. Several approaches were used to help ensure a beneficial initial clinical
      experience for medical students, while accepting that a uniform experience for
      all students was not attainable or necessary. Encouraging active learning on the
      part of students was a goal of IGC schools' planning in and of itself. The splash
      of establishing interdisciplinary communication structures and greater melding of
      disciplinary cultures that occurred at and among the IGC schools appeared to lead
      to ripple effects that were recognized within the first year of planning and
      early implementation.

PMID- 11299169
TI  - What did we learn about national organizational collaboration at the advisory
      committee level?
AB  - This article provides an overview of the typical roles and tasks of advisory
      groups in general, followed by a discussion of the roles and tasks the
      Interdisciplinary Generalist Curriculum (IGC) Project Advisory Committee was
      asked to assume and how these were fulfilled. It analyzes the lessons learned
      about advisory committees as a result of the IGC Project experience. Key elements
      of success in fulfilling advisory committee obligations include well-defined
      expectations, periodic evaluations, and clear communication between project
      leadership and the members of the advisory committee. In the spirit of lessons
      learned from the IGC Project, this critique identifies several philosophical and
      logistic issues that might be considered in the design and implementation of
      future projects, such as the need to choose committed, high-energy advisory
      committee members who are willing to perform many complex, time-consuming tasks.

PMID- 11299170
TI  - What did we learn about early clinical experience?
AB  - This article explores the lessons learned by ten demonstration schools regarding
      the early clinical experience (ECE) component of the Interdisciplinary Generalist
      Curriculum (IGC) PROJECT: Students in ECE at these schools participated in
      longitudinal, one-to-one or two-on-one preceptorships with primary care physician
      preceptors in outpatient settings. Development of an ECE was a key component of
      curricular change at each of the IGC Project schools. Shattering the traditional
      barrier between preclinical and clinical years of the 2 + 2 medical curriculum
      model helped create a leading edge for innovation at each of the schools. In this
      article, the authors incorporated evaluation information from several sources,
      including the external evaluation reports of the IGC Project, final annual
      reports from demonstration schools, and curriculum evaluations from the
      coauthors' schools (the University of Colorado School of Medicine, Nova
      Southeastern University College of Osteopathic Medicine, and the University of
      California, San Francisco School of Medicine).

PMID- 11299171
TI  - What did we learn about interdisciplinary collaboration in institutions?
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project significantly advanced
      collaboration in the development of medical school curricula. As primary care
      faculty began to work together they encountered and overcame many challenges
      inherent in this new process. Inclusion of other faculty and departments, as well
      as dedicated support from the deans' offices, became necessary to the success of
      the projects. The continuation of successful collaborative projects in the
      medical school environment requires a common commitment of faculty, students,
      department chairs, and the dean's office; protected time; and involvement of
      faculty from other disciplines. This article outlines initial models of
      collaboration implemented in the IGC Project, followed by a description of the
      expected and unexpected outcomes of these collaborative efforts, and a discussion
      of the emergence of new ways of collaborating, with recommendations for
      successful collaborative efforts.

PMID- 11299172
TI  - What did we learn about student and faculty "backlash" to the Interdisciplinary
      Generalist Curriculum Project?
AB  - There was student and faculty backlash against the Interdisciplinary Generalist
      Curriculum (IGC) Project innovations at all ten schools involved. Students may
      react strongly to requirements and experiences they find onerous, and often
      reacted to being "preached at" and being told what they should value and believe.
      Backlash was not limited to students. A complaint heard in virtually all schools
      was that the basic science faculty barely had enough time to adequately cover
      their topics as it was, and now they were being asked to give up time for
      clinical experiences and topics. Despite the backlash, the authors point out that
      the vast majority of students endorsed the value of the preceptorship experience
      and that reaction to the IGC Project did not necessarily translate into negative
      perceptions of primary care medicine. Each IGC Project school made strategic
      decisions in response to backlash. Among the various efforts undertaken were
      enhanced communication and clarification, persistence and "watchful waiting,"
      programmatic changes, and elimination of program components that were not
      working. These various efforts appear to have paid off, as most schools reported
      that backlash diminished over time. Lessons learned about backlash against new
      curricular innovations were that (1) backlash, however defined, is inevitable;
      (2) communication, coordination, and cooperation are essential; (3) flexibility,
      compromise, and willingness to change are essential; and (4) "watchful waiting"
      can be an effective response to some forms of backlash.

PMID- 11299173
TI  - What did we learn about the impact on students' clinical education?
AB  - Analysis of the impact of the Interdisciplinary Generalist Curriculum (IGC)
      Project would be incomplete without discussion of how it affected students'
      clinical education. This article explores the impact of the IGC Project on
      medical students' clinical education at the ten IGC schools. The schools
      typically lacked pre-IGC Project baseline data for comparison, although they all
      collected data on the impact of the new curriculum on the clinical education of
      students. Measures included some objective indicators and various subjective
      measures of the perceptions of the students, faculty, and community preceptors.
      The impact of curricular innovations at the IGC Project schools on students was
      immediate as they began to see patients early and continuously as part of their
      medical education. Students, faculty, and community preceptors who interacted
      with these students during their third year believed they were "different"
      because of their participation in the IGC. Not only did the IGC students approach
      patients with better integrated basic science knowledge, but also a different
      kind of student arrived at the third year, the traditional beginning of clinical
      experiences in medical education.

PMID- 11299174
TI  - What did we learn about the impact on university-based faculty?
AB  - Meeting the objectives and requirements of the Interdisciplinary Generalist
      Curriculum (IGC) Project had positive and negative effects on the university
      based basic science and clinical faculty, which have been divided into four
      categories: boundary issues, collaboration, teaching, and development. The
      specific experiences of two schools, the University of California, San Francisco,
      School of Medicine and the Joan C. Edwards School of Medicine at Marshall
      University, are compared against the experiences of the ten schools as documented
      in the IGC Project external evaluation team's final report. Boundary issues
      regarded as negative effects of the IGC Project included perceived encroachment
      on the time devoted to basic science education, loss of the unique identity of
      the university-based faculty as academicians, and reduced prominence of
      subspecialist clinical faculty. Effects of the IGC Project in the other areas
      were, for the most part, positive. The increased collaboration yielded a net
      benefit to the university-based faculty at large. The clinical faculty
      experienced more opportunities to teach. Introduction of teacher development
      programs were of benefit to both clinical and basic science faculty. The other
      arm of development, professional development, was evidenced by increased stature
      and promotions of IGC faculty directors. In conclusion, changes within the
      university-based faculty occurred in stages as faculty realized that the design
      of the IGC Project enhanced the educational experience of the students.

PMID- 11299175
TI  - What did we learn about the impact on community-based faculty? Recommendations
      for recruitment, retention, and rewards.
AB  - All ten schools participating in the Interdisciplinary Generalist Curriculum
      (IGC) Project were required to offer students significant generalist longitudinal
      preceptorship experiences during the first two years of medical school. Each
      school needed to recruit and then retain many new preceptors to meet the
      continued large demand. Effective recruitment was usually carried out by
      established community physicians and/or qualified staff coordinators. Retention
      of preceptors required establishing regular and succinct communications, quick
      response to problems, and flexible faculty development programs. For rewards,
      preceptors primarily requested acknowledgment and appreciation, along with
      tangible rewards such as decreased fees for continuing medical education and
      library or e-mail access. Preceptors continue to state that they teach because of
      the "joys of teaching" even in the current environment with increased demands for
      productivity. This article describes what has been learned about recruitment,
      retention, and rewards for community preceptors and how to maximize the positive
      impacts and minimize the negative impacts of teaching for community preceptors.

PMID- 11299176
TI  - What did we learn about leadership in medical education? Effecting institutional
      change through the Interdisciplinary Generalist Curriculum Project.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project required significant
      collaboration and cooperation at many levels of leadership to accommodate early
      clinical experiences in the curriculum. Three elements of institutional change
      are discussed: the context for desired early clinical experiences in medical
      education, structural elements required of the IGC Project schools, and
      leadership within the demonstration schools. Lessons learned from these
      interdisciplinary projects include the importance of supportive leadership from
      the top levels, establishing broad buy-in across sectors of the school, creating
      a team administrative structure that fosters participation by all groups, and
      central (rather than departmental) administration. The processes needed to
      establish collaborative leadership and full participation by the generalist
      departments and cooperation of diverse constituencies, such as basic science
      faculty, were labor-intensive and required more time to ensure successful program
      implementation. Uniformly, strong support at the highest levels of the
      organization, especially the medical schools' deans, was cited as a key element
      in the success of the IGC Project. An interesting unanticipated outcome of the
      project was the movement of the interdisciplinary course administration into a
      central location (dean's office) by the end of the project for all schools. This
      change may reflect a practical advantage for administration of interdisciplinary
      programs located at the level of the school or college, rather than housed within
      departments.

PMID- 11299177
TI  - The Interdisciplinary Generalist Curriculum Project at Eastern Virginia Medical
      School.
AB  - The proposed Interdisciplinary Generalist Curriculum (IGC) Project at Eastern
      Virginia Medical School (hereafter Eastern Virginia) intended to encourage
      students to select generalist disciplines by featuring generalist role models,
      focusing on patients' perspectives, teaching generalist skills early, providing
      care to indigent and other populations, and emphasizing students' personal and
      professional development. To do so, Eastern Virginia proposed that collaborative
      interdisciplinary groups of faculty plan and oversee the implementation of first-
      and second-year students' early clinical experiences in generalists' offices as
      integrated with new and revised first- and second-year courses, the coordination
      of generalist curricula longitudinally from year one through year four, and the
      provision of appropriate faculty development. With minor exceptions described,
      the project was implemented as proposed. The project did have desirable effects,
      both intended and unexpected. The curricular changes made in the project will
      remain.

PMID- 11299178
TI  - The Interdisciplinary Generalist Curriculum Project at Joan C. Edwards School of
      Medicine at Marshall University.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project was designed to enhance
      interest in and support of generalism during the first two years of medical
      education. The original goals at Joan C. Edwards School of Medicine at Marshall
      University included the design and implementation of a core curriculum,
      Introduction to Patient Care (IPC), and enhancement of teaching excellence
      through faculty development. The core curriculum facilitated integration with the
      basic sciences and early introduction of physical examination skills, which were
      further developed in longitudinal clinical experiences with mentors. Although it
      was not originally intended to include basic scientists in the preceptor groups,
      they became important additions and created additional opportunities for
      interdisciplinary teaching and reciprocal learning. The mentor program, another
      well-received and intended curriculum change, evolved from a structured
      experience to a more flexible component of the curriculum. The program met the
      requirements of the IGC Project but 53% of the originally intended mentor time
      was achievable, due to curriculum constraints. Faculty development, another
      success, was originally intended to target IPC faculty but ultimately became a
      university-wide effort. The changes implemented as a result of the IGC Project
      continue to flourish beyond the funding period and have become integral aspects
      of the curriculum and the medical school.

PMID- 11299179
TI  - The Interdisciplinary Generalist Curriculum Project at the Medical College of
      Ohio.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project at the Medical College
      of Ohio sought to develop and introduce a new required preclinical community
      based ambulatory experience and to incorporate existing clinically oriented
      courses in the first two years into one specific curriculum. The major portion of
      the IGC was the Introduction to Primary Care (IPC), which consisted of 180 hours
      of new and restructured curriculum time in the first and second years. It
      included a community-based ambulatory care experience involving students spending
      time with community-based preceptors, problem-based group discussions with two
      generalists of different backgrounds, patient-centered workshops in primary care
      during both first and second years, an in-depth experience in the first year for
      students who worked with preceptors for two full days, and the development of a
      two-day clinical assessment and feedback session just prior to entry into the
      third clinical year. The IGC Project progressed as planned with two major
      exceptions. The problem-based group discussions were difficult to coordinate with
      schedules of two physicians as well as the busy schedules of four students, and
      were adapted after the initial experience so that at least one preceptor attended
      each meeting. The second difficulty involved coordinating with other clinical
      departments to effect a true change in the culture of the institution.
      Nonetheless, as a result of having the IGC Project at the Medical College of
      Ohio, the curriculum has been revised to incorporate all of the basic IGC
      concepts and principles. Other results are the development of objective
      structured clinical examinations that are held at the end of the first and second
      years and institution of the primary care block in the third year, which have
      provided the impetus for the establishment of a clinical skills assessment
      center.

PMID- 11299180
TI  - The Interdisciplinary Generalist Curriculum Project at Nova Southeastern
      University College of Osteopathic Medicine.
AB  - Nova Southeastern University College of Osteopathic Medicine (Nova Southeastern)
      proposed for its IGC Project to match students with community-based generalist
      physician role models through partnership with a managed care organization (MCO).
      An unanticipated corporate merger between the initial managed care partner and
      another health plan resulted in Nova Southeastern's negotiating training
      partnerships with multiple MCOS: Other program elements that differed from what
      was originally proposed include provision of an interactive utilization
      management session at a hospital or skilled nursing facility, rather than a
      headquarters-based utilization management rotation; combining multiple learning
      experiences for students within a single MCO session; having a portion of the
      training take place at field-based sites outside MCO headquarters or after normal
      business hours (i.e., MCO physician committee meetings); and recruitment of
      physician mentors through a variety of means and not just through MCOS: The
      current goals emphasize preparing students to have a working knowledge of managed
      care principles and practice that can be applied in any medical field and
      setting. This goal contrasts with the original goal of preparing students for
      jobs "within" managed care. The IGC Project is viewed at Nova Southeastern as the
      flagship of interdisciplinary curricular changes in the training of tomorrow's
      physicians.

PMID- 11299181
TI  - The Interdisciplinary Generalist Curriculum Project at the University of
      California, San Francisco.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project came at a pivotal time
      in curriculum development at the University of California, San Francisco, School
      of MEDICINE: In the three years prior to the project, the curriculum committee
      had considered implementation of early longitudinal clinical experiences. This
      had not been proposed as a primary care experience. Introduction of generalist
      skills, with the goal of increasing numbers of students choosing generalist
      residencies, presented significant challenges at this tertiary care and research
      oriented medical school. The new IGC course, Foundations of Patient Care,
      consists of on-campus lectures, small-group sessions, physical examination skills
      instruction, and a six-quarter preceptorship. As proposed, the school increased
      teaching of generalist skills and competencies and developed a large pool of
      primary care preceptors. There was no change in the number of graduates choosing
      primary care. The strong collaboration that resulted from the development of this
      new course served as a catalyst for major curricular reform now under way at this
      medical school.

PMID- 11299182
TI  - The Interdisciplinary Generalist Curriculum Project at the University of Colorado
      School of Medicine.
AB  - The University of Colorado School of Medicine first considered a longitudinal
      primary care preceptorship in 1992, when the dean formed the dean's Ad Hoc
      Committee to launch the "generalist initiative," to include a three-year required
      longitudinal generalist preceptorship. Being awarded an Interdisciplinary
      Generalist Curriculum (IGC) Project contract provided the dean's Ad Hoc Committee
      with the momentum it needed to enact the curriculum. This article describes the
      IGC Project at the University of Colorado as it was originally proposed and the
      intended and unintended outcomes over time. Intended outcomes included
      establishing early continuous clinical experiences as a vital part of the
      curriculum and increased exposure to primary care, while examples of unintended
      outcomes were the development of a longitudinal skill and behavior evaluation
      process and the integration of problem-based learning in the curriculum. The
      article concludes with a description of what is ahead for the curriculum.

PMID- 11299183
TI  - The Interdisciplinary Generalist Curriculum Project at the University of Illinois
      at Chicago College of Medicine.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project was initiated at the
      University of Illinois at Chicago (UI-Chicago) College of Medicine to link an
      ongoing longitudinal primary care experience with a didactic curriculum
      emphasizing generalism. The result of this educational initiative was a more
      extensive reform of the preclinical curriculum than originally had been planned.
      The IGC Project catalyzed a critical analysis of the first- and second-year
      curriculum that continues and that has resulted in the integration of all of the
      early clinical course work under a single longitudinal curriculum. The IGC
      Project also established a model for interdisciplinary collaboration in course
      and curriculum design and expanded the walls of the university to include greater
      numbers of community-based generalist preceptors. This modestly funded and
      focused educational initiative had unanticipated and far-reaching implications
      for educational activities throughout the College of Medicine at UI-Chicago.

PMID- 11299184
TI  - The Interdisciplinary Generalist Project at the University of Nebraska Medical
      Center.
AB  - The Interdisciplinary Generalist Curriculum (IGC) Project at the University of
      Nebraska College of Medicine (Nebraska) had three goals: (1) to increase first-
      and second-year students' exposure to primary care practice in the community; (2)
      to develop specific educational programs introducing these students to the
      principles and practices of primary care medicine; and (3) to establish a
      generalist coordinating council to provide leadership and to nurture generalist
      educational initiatives in the College of MEDICINE: Students at Nebraska were
      already required to spend three half-days a semester in a longitudinal clinical
      experience (LCE) and to complete a three-week primary care block experience in
      the summer between the first and second years. IGC Project funds were used
      increase the number of required LCE visits to five a semester and to develop
      curricular enhancements that would maximize the educational potential of
      community-based clinical experiences for first- and second-year students.
      Curricular elements developed included a focus on faculty development for
      preceptors and development of the Primary Care Introduction to Medicine
      Curriculum, an eight-week, interdisciplinary module scheduled late in the first
      year to help prepare students for intensive summer rotations. Other developments
      were the implementation of a pediatric physical examination experience for first
      year students and the implementation of instruction in community-oriented primary
      care in the second year. Lessons learned are related to: (1) the value and power
      of early clinical experiences; and (2) the enhancing effect of a holistic,
      longitudinal view of the curriculum on the planning of early clinical
      experiences.

PMID- 11299185
TI  - The Interdisciplinary Generalist Curriculum Project at the University of Vermont
      College of Medicine: The Vermont Generalist Curriculum (VGC) Experience.
AB  - The University of Vermont College of Medicine received its Vermont Generalist
      Curriculum (VGC) subcontract as one of the second-cycle Interdisciplinary
      Generalist Curriculum (IGC) Project schools from 1995 to 1998. The Vermont
      program was jointly codirected by the chairs of family practice and pediatrics
      and the program director for internal medicine on a rotating basis and was
      overseen by a multidisciplinary steering committee that included generalists,
      basic scientists, specialists, and students. This committee provided guidance and
      support in recruitment of preceptors, continuous assessment and improvement of
      the courses, development of a clinical correlation manual for students in
      clinical offices, and cooperation around a jointly sponsored annual primary care
      meeting that included a joint scientific program, a research forum, and a faculty
      development workshop. The VGC has provided a pilot for many innovative curricular
      changes that have served as models for the school-wide curriculum redesign
      process currently under way at VERMONT: While the funding for this project ended
      in 1998, the changes, innovations, and collaboration born out of the project are
      valuable enough for the dean's office to maintain the VGC's funding and its
      steering committee for the future.

PMID- 11299186
TI  - The Interdisciplinary Generalist Curriculum Project at the University of
      Wisconsin Medical School: the Generalist Partners Program.
AB  - The Generalist Partners Program (GPP) provides all University of Wisconsin
      Medical School students with a comprehensive generalist core curriculum through
      early clinical experiences, interactive faculty presentations, and small-group
      discussions during the first two years of medical school. The GPP is the first
      component of a comprehensive, longitudinal generalist curriculum offered during
      all four years of medical education. Faculty members from family medicine,
      general internal medicine, and general pediatrics work together to develop the
      learning goals and provide the curriculum for the GPP courses. Each of the 145
      entering first-year medical students is matched with a community-based physician,
      the generalist practice partner, and the students participate in early clinical
      experiences at this site throughout their first two years of medical education.
      Students' clinical experiences are presented and discussed in case-based small
      group sessions led by the school's generalist faculty. A core lecture series on
      professionalism, communication skills, evidence-based medicine, and the
      organization of the health care system supplements the early clinical
      experiences.

PMID- 11299187
TI  - Recommendations to institutions.
AB  - Results from the Interdisciplinary Generalist Curriculum (IGC) Project support
      current ideas of management within a chaotic environment. Important aspects of
      building support for educational innovation included the following. The trend
      toward primary care and request for proposal process were important catalysts for
      change. Buy-in from the dean and key opinion leaders was essential. Early
      identification of champions for the proposal and ability to achieve broad
      consensus helped shape coherent projects. Being able to read the culture of the
      institution and accede to pragmatic changes were important for bridging the
      initial implementation and maintenance of the change. IGC Project leaders were
      quick to identify key leverage points, both internal and external. The
      recommendations of key school committees and licensing bodies were used to foster
      ongoing change. A respected home for the project on neutral ground was sought.
      Dedicated coordinators helped sustain daily details, while developing rewards and
      recognition for collaboration supported faculty involvement. New relationships
      fostered new systems, which the projects used to continue after funding lapsed
      and to successfully apply for other grants and contracts.

PMID- 11299188
TI  - Curricular change: recommendations from a national perspective.
AB  - Recommendations on future directions, funding, and organizational and curricular
      issues have emerged from the complexity of the Interdisciplinary Generalist
      Curriculum (IGC) Project. For example, future demonstration projects aimed at
      innovations in medical education that are funded through the contracting
      mechanism are recommended, and funding intended to serve as institutional
      leverage for demonstrating desired curricular innovations in medical education is
      encouraged. Funding provided to entities that can maximize influence within the
      institutions is recommended. Also, the period of time over which funds are
      provided needs to take into consideration the breadth of the impact of the funded
      program on the larger curriculum and the length of time needed to measure desired
      outcomes. Organizational findings are that multi-site projects with
      administrative oversight bodies should be governed by representatives of
      concerned disciplines who have stakes in the demonstration of the innovations in
      medical education, and roles of the executive and advisory committees involved in
      the effort need to be made explicit at the onset and revisited over time.
      Similarly, the role of the funder needs to be explicit. Curricular
      recommendations are that medical schools are encouraged to develop longitudinal
      generalist preceptorship experiences early in medical education for all students,
      regardless of their eventual career choices. Schools should anticipate that
      curricular innovations in the preclinical years may require modifications of the
      educational process in the clinical years.

PMID- 11299191
TI  - Therapeutic coronary angiogenesis: a fronte praecipitium a tergo lupi?

PMID- 11299192
TI  - Cardiac excitation-contraction coupling: role of membrane potential in regulation
      of contraction.
AB  - The steps that couple depolarization of the cardiac cell membrane to initiation
      of contraction remain controversial. Depolarization triggers a rise in
      intracellular free Ca(2+) which activates contractile myofilaments. Most of this
      Ca(2+) is released from the sarcoplasmic reticulum (SR). Two fundamentally
      different mechanisms have been proposed for SR Ca(2+) release: Ca(2+)-induced
      Ca(2+) release (CICR) and a voltage-sensitive release mechanism (VSRM). Both
      mechanisms operate in the same cell and may contribute to contraction. CICR
      couples the release of SR Ca(2+) closely to the magnitude of the L-type Ca(2+)
      current. In contrast, the VSRM is graded by membrane potential rather than Ca(2+)
      current. The electrophysiological and pharmacological characteristics of the VSRM
      are strikingly different from CICR. Furthermore, the VSRM is strongly modulated
      by phosphorylation and provides a new regulatory mechanism for cardiac
      contraction. The VSRM is depressed in heart failure and may play an important
      role in contractile dysfunction. This review explores the operation and
      characteristics of the VSRM and CICR and discusses the impact of the VSRM on our
      understanding of cardiac excitation-contraction coupling.

PMID- 11299193
TI  - Progressive loss of perfusion-contraction matching during sustained moderate
      ischemia in pigs.
AB  - It is unclear whether perfusion-contraction matching (PCM) is maintained during
      prolonged myocardial ischemia. In 27 anesthetized pigs, left anterior descending
      coronary arterial inflow was reduced to decrease an anterior work index (WI) at 5
      min of hypoperfusion by 40% and then maintained at this level for 12 or 24 h.
      With 12 h of hypoperfusion, the myocardium remained viable in 6 of 7 pigs (with
      triphenyltetrazolium chloride; TTC) and with 24 h of hypoperfusion in 5 of 11
      pigs (TTC, histology). The reduction in WI to 62 +/- 4 and 62 +/- 3% of baseline
      in the two groups was matched to the reduction of transmural blood flow (TBF;
      microspheres) at 5 min of hypoperfusion, averaging 59 +/- 4 and 60 +/- 2% of
      baseline. With prolonged hypoperfusion, WI decreased to 30 +/- 5% at 12 h and 18
      +/- 3% at 24 h; TBF remained unchanged (53 +/- 4 and 54 +/- 4%). The added
      calcium concentration required for the half-maximal increase in WI increased from
      121 +/- 25 microg/ml blood at baseline to 192 +/- 26 microg/ml blood at 12 h of
      hypoperfusion. Thus, with hypoperfusion for 24 h, PCM is progressively lost, and
      calcium responsiveness is reduced.

PMID- 11299194
TI  - Accuracy of echocardiographic estimates of left ventricular mass in mice.
AB  - Genetically modified mice have created the need for accurate noninvasive left
      ventricular mass (LVM) measurements. Recent technical advances provide two
      dimensional images adequate for LVM calculation using the area-length method,
      which in humans is more accurate than M-mode methods. We compared the standard M
      mode and area-length methods in mice over a wide range of LV sizes and weights
      (62-210 mg). Ninety-one CD-1 mice (38 normal, 44 aortic banded, and 9 inherited
      dilated cardiomyopathy) were imaged transthoracically (15 MHz linear transducer,
      120 Hz). Compared with necropsy weights, area-length measurements showed higher
      correlation than the M-mode method (r = 0.92 vs. 0.81), increased accuracy (bias
      +/- SD: 1.4 +/- 27.1% vs. 36.7 +/- 51.6%), and improved reproducibility. There
      was no significant difference between end-systolic and end-diastolic estimates.
      The truncated ellipsoid estimation produced results similar in accuracy to the
      area-length method. Whereas current echocardiographic technology can accurately
      and reproducibly estimate LVM with the two-dimensional, area-length formula in a
      variety of mouse models, additional technological improvements, rather than
      refinement of geometric models, will likely improve the accuracy of this
      methodology.

PMID- 11299195
TI  - Leukocyte-type 12-lipoxygenase-deficient mice show impaired ischemic
      preconditioning-induced cardioprotection.
AB  - To investigate the role of 12-lipoxygenase in preconditioning, we examined
      whether hearts lacking the "leukocyte-type" 12-lipoxygenase (12-LOKO) would be
      protected by preconditioning. In hearts from wild-type (WT) and 12-LOKO mice,
      left ventricular developed pressure (LVDP) and (31)P NMR were monitored during
      treatment (+/-preconditioning) and during global ischemia and reperfusion.
      Postischemic function (rate-pressure product, percentage of initial value)
      measured after 20 min of ischemia and 40 min of reperfusion was significantly
      improved by preconditioning in WT hearts (78 +/- 12% in preconditioned vs. 44 +/-
      7% in nonpreconditioned hearts) but not in 12-LOKO hearts (47 +/- 7% in
      preconditioned vs. 33 +/- 10% in nonpreconditioned hearts). Postischemic recovery
      of phosphocreatine was significantly better in WT preconditioned hearts than in
      12-LOKO preconditioned hearts. Preconditioning significantly reduced the fall in
      intracellular pH during sustained ischemia in both WT and 12-LOKO hearts,
      suggesting that attenuation of the fall in pH during ischemia can be dissociated
      from preconditioning-induced protection. Necrosis was assessed after 25 min of
      ischemia and 2 h of reperfusion using 2,3,5-triphenyltetrazolium chloride. In WT
      hearts, preconditioning significantly reduced the area of necrosis (26 +/- 4%)
      compared with nonpreconditioned hearts (62 +/- 10%) but not in 12-LOKO hearts (85
      +/- 3% in preconditioned vs. 63 +/- 11% in nonpreconditioned hearts).
      Preconditioning resulted in a significant increase in 12(S)
      hydroxyeicosatetraenoic acid in WT but not in 12-LOKO hearts. These data
      demonstrate that 12-lipoxygenase is important in preconditioning.

PMID- 11299196
TI  - Role of p38 mitogen-activated protein kinase in cardiac myocyte secretion of the
      inflammatory cytokine TNF-alpha.
AB  - This study examined the hypothesis that burn trauma promotes cardiac myocyte
      secretion of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and
      produces cardiac contractile dysfunction via the p38 mitogen-activated protein
      kinase (MAPK) pathway. Sprague-Dawley rats were divided into four groups: 1) sham
      burn rats given anesthesia alone, 2) sham burn rats given the p38 MAPK inhibitor
      SB203580 (6 mg/kg po, 15 min; 6- and 22-h postburn), 3) rats given third-degree
      burns over 40% total body surface area and treated with vehicle (1 ml of saline)
      plus lactated Ringer solution for resuscitation (4 ml x kg(-1). percent burn(
      1)), and 4) burn rats given injury and fluid resuscitation plus SB203580. Rats
      from each group were killed at several times postburn to examine p38 MAPK
      activity (by Western blot analysis or in vitro kinase assay); myocardial function
      and myocyte secretion of TNF-alpha were examined at 24-h postburn. These studies
      showed significant activation of p38 MAPK at 1-, 2-, and 4-h postburn compared
      with time-matched shams. Burn trauma impaired cardiac mechanical performance and
      promoted myocyte secretion of TNF-alpha. SB203580 inhibited p38 MAPK activity,
      reduced myocyte secretion of TNF-alpha, and prevented burn-mediated cardiac
      deficits. These data suggest p38 MAPK activation is one aspect of the signaling
      cascade that culminates in postburn secretion of TNF-alpha and contributes to
      postburn cardiac dysfunction.

PMID- 11299197
TI  - Parameters of red blood cell aggregation as correlates of the inflammatory state.
AB  - To identify clinically relevant parameters of red blood cell (RBC) aggregation,
      we examined correlations of aggregation parameters with C-reactive protein and
      fibrinogen in unstable angina (UA), acute myocardial infarction (AMI), and
      bacterial infection (BI). Aggregation parameters were derived from the
      distribution of RBC population into aggregate sizes (cells per aggregate) and
      changing of the distribution by flow-derived shear stress. Increased aggregation
      was observed in the following order: UA, AMI, and BI. The best correlation was
      obtained by integration of large aggregate fraction as a function of shear
      stress. To differentiate plasmatic from cellular factors in RBC aggregation, we
      determined the aggregation in the presence and absence of plasma and formulated a
      "plasma factor" (PF) ranging from 0 to 1. In AMI the enhanced aggregation was
      entirely due to PF (PF = 1), whereas in UA and BI it was due to both plasmatic
      and cellular factors (0 < or = PF < or = 1). It is proposed that clinically
      relevant parameters of RBC aggregation should express both RBC aggregate size
      distribution and aggregate resistance to disaggregation and distinguish between
      plasmatic and cellular factors.

PMID- 11299198
TI  - Lack of muscarinic regulation of Ca(2+) channels in G(i2)alpha gene knockout
      mouse hearts.
AB  - The purpose of the present study was to examine the role of G(i2)alpha in Ca(2+)
      channel regulation using G(i2)alpha gene knockout mouse ventricular myocytes. The
      whole cell voltage-clamp technique was used to study the effects of the
      muscarinic agonist carbachol (CCh) and the beta-adrenergic agonist isoproterenol
      (Iso) on cardiac L-type Ca(2+) currents in both 129Sv wild-type (WT) and
      G(i2)alpha gene knockout (G(i2)alpha-/-) mice. Perfusion with CCh significantly
      inhibited the Ca(2+) current in WT cells, and this effect was reversed by adding
      atropine to the CCh-containing solution. In contrast, CCh did not affect Ca(2+)
      currents in G(i2)alpha-/- ventricular myocytes. Addition of CCh to Iso-containing
      solutions attenuated the Iso-stimulated Ca(2+) current in WT cardiomyocytes but
      not in G(i2)alpha-/- cells. These findings demonstrate that, whereas the Iso
      G(s)alpha signal pathway is intact in G(i2)alpha gene knockout mouse hearts,
      these cells lack the inhibitory regulation of Ca(2+) channels by CCh. Therefore,
      G(i2)alpha is necessary for the muscarinic regulation of Ca(2+) channels in the
      mouse heart. Further studies are needed to delineate the possible interaction of
      G(i) and other cell signaling proteins and to clarify the level of interaction of
      G protein-coupled regulation of L-type Ca(2+) current in the heart.

PMID- 11299199
TI  - AT1 receptor block does not affect arterial baroreflex during pregnancy in
      rabbits.
AB  - The role of ANG II in the arterial baroreflex control of renal sympathetic nerve
      activity (RSNA) in eight term-pregnant (P) and eight nonpregnant (NP) conscious
      rabbits was assessed using sequential intracerebroventricular and intravenous
      infusions of losartan, an AT1 receptor antagonist. The blood pressure (BP)-RSNA
      relationship was generated by sequential inflations of aortic and vena caval
      perivascular occluders. Pregnant rabbits exhibited a lower maximal RSNA reflex
      gain (-44%) that was primarily due to a reduction in the maximal sympathetic
      response to hypotension (P, 248 +/- 20% vs. NP, 357 +/- 41% of rest RSNA, P <
      0.05). Intracerebroventricular losartan decreased resting BP in P (by 9 +/- 3
      mmHg, P < 0.05) but not NP rabbits, and had no effect on the RSNA baroreflex in
      either group. Subsequent intravenous losartan decreased resting BP in NP and
      further decreased BP in P rabbits, but had no significant effect on the maximal
      RSNA reflex gain. ANG II may have an enhanced role in the tonic support of BP in
      pregnancy, but does not mediate the gestational depression in the arterial
      baroreflex control of RSNA in rabbits.

PMID- 11299200
TI  - Direct biologically based biosensing of dynamic physiological function.
AB  - Dynamic regulation of biological systems requires real-time assessment of
      relevant physiological needs. Biosensors, which transduce biological actions or
      reactions into signals amenable to processing, are well suited for such
      monitoring. Typically, in vivo biosensors approximate physiological function via
      the measurement of surrogate signals. The alternative approach presented here
      would be to use biologically based biosensors for the direct measurement of
      physiological activity via functional integration of relevant governing inputs.
      We show that an implanted excitable-tissue biosensor (excitable cardiac tissue)
      can be used as a real-time, integrated bioprocessor to analyze the complex inputs
      regulating a dynamic physiological variable (heart rate). This approach offers
      the potential for long-term biologically tuned quantification of endogenous
      physiological function.

PMID- 11299201
TI  - Effects of luminal shear stress on cerebral arteries and arterioles.
AB  - The effect of luminal shear stress was studied in cerebral arteries and
      arterioles. Middle cerebral arteries (MCA) and penetrating arterioles (PA) were
      isolated from male Long-Evans rats, mounted in a tissue bath, and pressurized.
      After the development of spontaneous tone, inside diameters were 186 +/- 5 microm
      (n = 28) for MCA and 65 +/- 3 microm (n = 37) for PA. MCA and PA constricted
      approximately 20% with increasing flow. Flow-induced constriction persisted in
      MCA and PA after removal of the endothelium. After removal of the endothelium,
      the luminal application of a polypeptide containing the Arg-Gly-Asp amino acid
      sequence (inhibitor of integrin attachment) abolished the flow-induced
      constriction. Similarly, an antibody specific for the beta(3)-chain of the
      integrin complex significantly inhibited the flow-induced constriction. The shear
      stress-induced constriction was accompanied by an increase in vascular smooth
      muscle Ca(2+). For example, a shear stress of 20 dyn/cm(2) constricted MCA 8% (n
      = 5) and increased Ca(2+) from 209 +/- 17 to 262 +/- 29 nM (n = 5). We conclude
      that isolated cerebral arteries and arterioles from the rat constrict to
      increased shear stress. Because the endothelium is not necessary for the
      response, the shear forces must be transmitted across the endothelium, presumably
      by the cytoskeletal matrix, to elicit constriction. Integrins containing the
      beta(3)-chain are involved with the shear stress-induced constrictions.

PMID- 11299202
TI  - COX-2-dependent delayed dilatation of cerebral arterioles in response to
      bradykinin.
AB  - Bradykinin (BK) is released in the brain during injury and inflammation.
      Activation of endothelial BK receptors produces acute dilatation of cerebral
      arterioles that is mediated by reactive oxygen species (ROS). ROS can also
      modulate gene expression, including expression of the inducible isoform of
      cyclooxygenase (COX-2). We hypothesized that exposure of the brain to BK would
      produce acute dilatation, which would be followed by a delayed dilatation
      mediated by COX-2. To test this hypothesis in anesthetized rats, BK was placed
      twice in cranial windows for 7 min, after which the windows were flushed to
      remove residual BK. The two BK exposures were separated by 30 min. Each BK
      exposure produced acute dilatation of cerebral arterioles, after which diameter
      rapidly returned to baseline. Over the subsequent 4.5 h after the second BK
      exposure, arterioles dilated 48 +/- 8%. Treatment of the cranial window with NS
      398, a selective COX-2 inhibitor, or dexamethasone, significantly attenuated the
      delayed dilatation. Aminoguanidine, a selective inhibitor of inducible nitric
      oxide synthase, did not alter the delayed dilatation. Cotreatment of cranial
      windows with BK, superoxide dismutase, and catalase also prevented the delayed
      dilatation. In separate experiments, exposure of the cortical surface to BK
      upregulated leptomeningeal expression of COX-2 mRNA. Our results suggest that
      acute, time-limited exposure of the brain to BK produces delayed dilatation of
      cerebral arterioles dependent on expression and activity of COX-2.

PMID- 11299203
TI  - Oxygen supply and oxidative phosphorylation limitation in rat myocardium in situ.
AB  - The 1H-NMR signal of the proximal histidyl-N(delta)H of deoxymyoglobin is
      detectable in the in situ rat myocardium and can reflect the intracellular PO2.
      Under basal normoxic conditions, the cellular PO2 is sufficient to saturate
      myoglobin (Mb). No proximal histidyl signal of Mb is detectable. On ligation of
      the left anterior descending coronary artery, the Mb signal at 78 parts/million
      (ppm) appears, along with a peak shoulder assigned to the corresponding signal of
      Hb. During dopamine infusion up to 80 microg. kg(-1) x min(-1), both the heart
      rate-pressure product (RPP) and myocardial oxygen consumption (MVO2) increase by
      about a factor of 2. Coronary flow increases by 84%, and O2 extraction
      (arteriovenous O2 difference) rises by 31%. Despite the increased respiration and
      work, no deoxymyoglobin signal is detected, implying that the intracellular O2
      level still saturates MbO2, well above the PO2 at 50% saturation of Mb. The
      phosphocreatine (PCr) level decreases, however, during dopamine stimulation, and
      the ratio of the change in P(i) over PCr (DeltaP(i)/PCr) increases by 0.19.
      Infusion of either pyruvate, as the primary substrate, or dichloroacetate, a
      pyruvate dehydrogenase activator, abolishes the change in DeltaP(i)/PCr.
      Intracellular O2 supply does not limit MVO2, and the role of ADP in regulating
      respiration in rat myocardium in vivo remains an open question.

PMID- 11299204
TI  - AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1/IsK channel complex.
AB  - In cardiac myocytes, the slow component of the delayed rectifier K(+) current
      (I(Ks)) is regulated by cAMP. Elevated cAMP increases I(Ks) amplitude, slows its
      deactivation kinetics, and shifts its activation curve. At the molecular level,
      I(Ks) channels are composed of KvLQT1/IsK complexes. In a variety of mammalian
      heterologous expression systems maintained at physiological temperature, we
      explored cAMP regulation of recombinant KvLQT1/IsK complexes. In these systems,
      KvLQT1/IsK complexes were totally insensitive to cAMP regulation. cAMP regulation
      was not restored by coexpression with the dominant negative isoform of KvLQT1 or
      with the cystic fibrosis transmembrane regulator. In contrast, coexpression of
      the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP
      (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes
      inasmuch as cAMP stimulation increased the I(Ks) amplitude, increased its
      deactivation time constant, and negatively shifted its activation curve. However,
      in cells expressing an AKAP, the effects of cAMP stimulation on the I(Ks)
      amplitude remained modest compared with those previously reported in cardiac
      myocytes. The effects of cAMP stimulation were fully prevented by including the
      Ht31 peptide (a global disruptor of protein kinase A anchoring) in the
      intracellular medium. We concluded that cAMP regulation of I(Ks) requires protein
      kinase A anchoring by AKAPs, which therefore participate with the channel protein
      complex underlying I(Ks).

PMID- 11299205
TI  - Impaired sarcoplasmic reticulum function leads to contractile dysfunction and
      cardiac hypertrophy.
AB  - Sarcoplasmic reticulum (SR)-mediated Ca(2+) sequestration and release are
      important determinants of cardiac contractility. In end-stage heart failure SR
      dysfunction has been proposed to contribute to the impaired cardiac performance.
      In this study we tested the hypothesis that a targeted interference with SR
      function can be a primary cause of contractile impairment that in turn might
      alter cardiac gene expression and induce cardiac hypertrophy. To study this we
      developed a novel animal model in which ryanodine, a substance that alters SR
      Ca(2+) release, was added to the drinking water of mice. After 1 wk of treatment,
      in vivo hemodynamic measurements showed a 28% reduction in the maximum speed of
      contraction (+dP/dt(max)) and a 24% reduction in the maximum speed of relaxation
      (-dP/dt(max)). The slowing of cardiac relaxation was confirmed in isolated
      papillary muscles. The late phase of relaxation expressed as the time from 50% to
      90% relaxation was prolonged by 22%. After 4 wk of ryanodine administration the
      animals had developed a significant cardiac hypertrophy that was most prominent
      in both atria (right atrium +115%, left atrium +100%, right ventricle +23%, and
      left ventricle +13%). This was accompanied by molecular changes including a
      threefold increase in atrial natriuretic factor mRNA and a sixfold increase in
      beta-myosin heavy chain mRNA. Sarcoplasmic endoplasmic reticulum Ca(2+) mRNA was
      reduced by 18%. These data suggest that selective impairment of SR function in
      vivo can induce changes in cardiac gene expression and promote cardiac growth.

PMID- 11299206
TI  - Mapping action potentials and calcium transients simultaneously from the intact
      heart.
AB  - Intracellular calcium handling plays an important role in cardiac
      electrophysiology. Using two fluorescent indicators, we developed an optical
      mapping system that is capable of measuring calcium transients and action
      potentials at 256 recording sites simultaneously from the intact guinea pig
      heart. On the basis of in vitro measurements of dye excitation and emission
      spectra, excitation and emission filters at 515 +/- 5 and >695 nm, respectively,
      were used to measure action potentials with di-4-ANEPPS, and excitation and
      emission filters at 365 +/- 25 and 485 +/- 5 nm, respectively, were used to
      measure calcium transients with indo 1. The percent error due to spectral overlap
      was small when action potentials were measured (1.7 +/- 1.0%, n = 3) and
      negligible when calcium transients were measured (0%, n = 3). Recordings of
      calcium transients, action potentials, and isochrone maps of depolarization time
      and the time of calcium transient onset indicated negligible error due to
      fluorescence emission overlap. These data demonstrate that the error due to
      spectral overlap of indo 1 and di-4-ANEPPS is sufficiently small, such that
      optical mapping techniques can be used to measure calcium transients and action
      potentials simultaneously in the intact heart.

PMID- 11299207
TI  - Thyroid status influences baroreflex function and autonomic contributions to
      arterial pressure and heart rate.
AB  - The effect of thyroid status on arterial baroreflex function and autonomic
      contributions to resting blood pressure and heart rate (HR) were evaluated in
      conscious rats. Rats were rendered hyperthyroid (Hyper) or hypothyroid (Hypo)
      with triiodothyronine and propylthiouracil treatments, respectively. Euthyroid
      (Eut), Hyper, and Hypo rats were chronically instrumented to measure mean
      arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA).
      Baroreflex function was evaluated with the use of a logistic function that
      relates LSNA or HR to MAP during infusion of phenylephrine and sodium
      nitroprusside. Contributions of the autonomic nervous system to resting MAP and
      HR were assessed by blocking autonomic outflow with trimethaphan. In Hypo rats,
      the arterial baroreflex curve for both LSNA and HR was shifted downward. Hypo
      animals exhibited blunted sympathoexcitatory and tachycardic responses to
      decreases in MAP. Furthermore, the data suggest that in Hypo rats, the
      sympathetic influence on HR was predominant and the autonomic contribution to
      resting MAP was greater than in Eut rats. In Hyper rats, arterial baroreflex
      function generally was similar to that in Eut rats. The autonomic contribution to
      resting MAP was not different between Hyper and Eut rats, but predominant
      parasympathetic influence on HR was exhibited in Hyper rats. The results
      demonstrate baroreflex control of LSNA and HR is attenuated in Hypo but not Hyper
      rats. Thyroid status alters the balance of sympathetic to parasympathetic tone in
      the heart, and the Hypo state increases the autonomic contributions to resting
      blood pressure.

PMID- 11299208
TI  - Pregnancy enhances G protein activation and nitric oxide release from uterine
      arteries.
AB  - We hypothesized that pregnancy modulates receptor-mediated responses of the
      uterine artery (UA) by altering G protein activation or coupling. Relaxation and
      contraction to NaF (0.5-11.5 mM), acetylcholine (10(-9)-10(-5) M), and bradykinin
      (10(-12)-3 x 10(-5) M) were measured in isolated UA of pregnant and nonpregnant
      guinea pigs. Responses were measured in the presence and absence of either
      cholera toxin (2 microg/ml) or pertussis toxin (Galpha(s) and Galpha(i)
      inhibitors, respectively). NaF relaxation was endothelium dependent and nitro-L
      arginine sensitive (a nitric oxide synthase inhibitor). Relaxation to NaF,
      acetylcholine, and bradykinin were potentiated by pregnancy. Cholera but not
      pertussis toxin increased relaxation to acetylcholine and bradykinin in UA from
      nonpregnant animals, had no effect in UA from pregnant animals, and abolished the
      pregnancy-induced differences in acetylcholine relaxation. Cholera toxin
      potentiated the bradykinin-induced contraction of UA of both pregnant and
      nonpregnant animals, whereas pertussis toxin inhibited contraction of UA from
      pregnant animals only. Therefore, pregnancy may enhance agonist-stimulated
      endothelium-dependent relaxation and bradykinin-induced contraction of UA by
      inhibiting GTPase activity or enhancing Galpha(s) but not Galpha(i) activation in
      pregnant animals. Thus the diverse effects of pregnancy on UA responsiveness may
      result from hormonal modulation of G proteins coupled to their specific
      receptors.

PMID- 11299209
TI  - Modeling of the Norwood circulation: effects of shunt size, vascular resistances,
      and heart rate.
AB  - Hypoplastic left heart syndrome is the most common lethal cardiac malformation of
      the newborn. Its treatment, apart from heart transplantation, is the Norwood
      operation. The initial procedure for this staged repair consists of
      reconstructing a circulation where a single outlet from the heart provides
      systemic perfusion and an interpositioning shunt contributes blood flow to the
      lungs. To better understand this unique physiology, a computational model of the
      Norwood circulation was constructed on the basis of compartmental analysis.
      Influences of shunt diameter, systemic and pulmonary vascular resistance, and
      heart rate on the cardiovascular dynamics and oxygenation were studied.
      Simulations showed that 1) larger shunts diverted an increased proportion of
      cardiac output to the lungs, away from systemic perfusion, resulting in poorer O2
      delivery, 2) systemic vascular resistance exerted more effect on hemodynamics
      than pulmonary vascular resistance, 3) systemic arterial oxygenation was
      minimally influenced by heart rate changes, 4) there was a better correlation
      between venous O2 saturation and O2 delivery than between arterial O2 saturation
      and O2 delivery, and 5) a pulmonary-to-systemic blood flow ratio of 1 resulted in
      optimal O2 delivery in all physiological states and shunt sizes.

PMID- 11299210
TI  - Endothelial microtubule disruption blocks flow-dependent dilation of arterioles.
AB  - The cytoskeleton is believed to have an important role in the structural and
      functional integrity of endothelial cells. The role of the endothelial
      cytoskeleton, specifically microtubules, in the mediation of flow-induced
      dilation of arterioles has not yet been studied. Thus the aim of our study was to
      investigate the role of microtubules in the endothelial mechanotransduction of
      flow-induced dilation of isolated gracilis arterioles of the rat. The active
      diameter of arterioles at a constant perfusion pressure (80 mmHg) was
      approximately 63 microm, whereas their passive diameter (Ca(2+)-free solution)
      was approximately 119 microm. At a constant pressure, increases in flow of the
      perfusate solution (from 0 to 10 and from 10 to 20 microl/min) elicited increases
      in diameter up to approximately 95 microm (approximately a 53% increase).
      Intraluminal administration of nocodazole at concentrations of 5 x 10(-9) and 5 x
      10(-8) M had no discernible effects on the structure of endothelial microtubules
      or on flow-induced dilation, whereas it disassembled microtubules and eliminated
      flow-induced dilation at a concentration of 5 x 10(-7) M. At this higher
      concentration, however, the basal diameter and dilations to acetylcholine (10(-8)
      M), sodium nitroprusside (10(-7) M), arachidonic acid (5 x 10(-6) M), and
      prostaglandin E2 (10(-8) M) were unaffected. Colchicine (5 x 10(-7) M) also
      disassembled microtubules and eliminated flow-induced dilation. We concluded
      that, in isolated arterioles, the integrity of the endothelial cytoskeleton is
      essential for the transduction of the shear stress signal that results in the
      release of endothelial factors evoking dilation.

PMID- 11299211
TI  - Calorie restriction attenuates inflammatory responses to myocardial ischemia
      reperfusion injury.
AB  - The life-prolonging effects of calorie restriction (CR) may be due to reduced
      damage from cumulative oxidative stress. Our goal was to determine the long-term
      effects of moderate dietary CR on the myocardial response to reperfusion after a
      single episode of sublethal ischemia. Male Fisher 344 rats were fed either an ad
      libitum (AL) or CR (40% less calories) diet. At age 12 mo the animals were
      anaesthetized and subjected to thoracotomy and a 15-min left-anterior descending
      coronary artery occlusion. The hearts were reperfused for various periods. GSH
      and GSSG levels, nuclear factor-kappaB (NF-kappaB) DNA binding activity,
      cytokine, and antioxidant enzyme expression were assessed in the ischemic zones.
      Sham-operated animals served as controls. Compared with the AL diet, chronic CR
      limited oxidative stress as seen by rapid recovery in GSH levels in previously
      ischemic myocardium. CR reduced DNA binding activity of NF-kappaB. The kappaB
      responsive cytokines interleukin-1beta and tumor necrosis factor-alpha were
      transiently expressed in the CR group but persisted longer in the AL group.
      Furthermore, expression of manganese superoxide dismutase, a key antioxidant
      enzyme, was significantly delayed in the AL group. Collectively these data
      indicate that CR significantly attenuates myocardial oxidative stress and the
      postischemic inflammatory response.

PMID- 11299212
TI  - Gap junctions in the rabbit sinoatrial node.
AB  - In comparison to the cellular basis of pacemaking, the electrical interactions
      mediating synchronization and conduction in the sinoatrial node are poorly
      understood. Therefore, we have taken a combined immunohistochemical and
      electrophysiological approach to characterize gap junctions in the nodal area. We
      report that the pacemaker myocytes in the center of the rabbit sinoatrial node
      express the gap junction proteins connexin (Cx)40 and Cx46. In the periphery of
      the node, strands of pacemaker myocytes expressing Cx43 intermingle with strands
      expressing Cx40 and Cx46. Biophysical properties of gap junctions in isolated
      pairs of pacemaker myocytes were recorded under dual voltage clamp with the use
      of the perforated-patch method. Macroscopic junctional conductance ranged between
      0.6 and 25 nS with a mean value of 7.5 nS. The junctional conductance did not
      show a pronounced sensitivity to the transjunctional potential difference. Single
      channel recordings from pairs of pacemaker myocytes revealed populations of
      single-channel conductances at 133, 202, and 241 pS. With these single-channel
      conductances, the observed average macroscopic junctional conductance, 7.5 nS,
      would require only 30-60 open gap junction channels.

PMID- 11299213
TI  - In vivo chemotactic properties and spatial expression of PDGF in developing
      mesenteric microvascular networks.
AB  - The recruitment of perivascular cells to developing microvessels is a key
      component of microvessel assembly. Whereas platelet-derived growth factor (PDGF)
      signaling is critical for this process during embryonic development, its role
      from the postnatal stages through adulthood remains unclear. We investigated the
      potential role of PDGF signaling during microvessel assembly by measuring in vivo
      the migration of labeled fibroblasts to PDGF in mesenteric connective tissue and
      by examining PDGF-B and PDGF receptor-beta (PGDFR-beta) expression in
      microvascular networks during normal maturation. PDGF-B homodimer (PDGF-BB; 30
      ng/ml) application elicited a significant (P < 0.05) increase (7.8 +/- 4.1 cells)
      in labeled fibroblasts within 100 microm of the source micropipette after 2 h.
      PDGF-A homodimer (30 ng/ml) application and control solution did not elicit
      directed migration. PDGF-B was expressed in microvessel endothelium and smooth
      muscle, whereas PDGFR-beta was expressed in endothelium, smooth muscle, and
      interstitial fibroblasts. Given that PDGF-BB elicits fibroblast migration in the
      mesentery and that PDGF-B and PDGFR-beta are expressed in a pattern that
      indicates paracrine signaling from microvessels to the interstitium, the results
      are consistent with a role for PDGF-B in perivascular cell recruitment to
      microvessels.

PMID- 11299214
TI  - Oxidative burst and NO generation as initial response to ischemia in flow-adapted
      endothelial cells.
AB  - Shear stress modulates endothelial physiology, yet the effect(s) of flow
      cessation is poorly understood. The initial metabolic responses of flow-adapted
      bovine pulmonary artery endothelial cells to the abrupt cessation of flow
      (simulated ischemia) was evaluated using a perfusion chamber designed for
      continuous spectroscopy. Plasma membrane potential, production of reactive O2
      species (ROS), and intracellular Ca(2+) and nitric oxide (NO) levels were
      measured with fluorescent probes. Within 15 s after flow cessation, flow-adapted
      cells, but not cells cultured under static conditions, showed plasma membrane
      depolarization and an oxidative burst with generation of ROS that was inhibited
      by diphenyleneiodonium. EGTA-inhibitable elevation of intracellular Ca(2+) and NO
      were observed at approximately 30 and 60 s after flow cessation, respectively. NO
      generation was decreased in the presence of inhibitors of NO synthase and
      calmodulin. Thus flow-adapted endothelial cells sense the altered hemodynamics
      associated with flow cessation and respond by plasma membrane depolarization,
      activation of NADPH oxidase, Ca(2+) influx, and activation of Ca(2+)/calmodulin
      dependent NO synthase. This signaling response is unrelated to cellular anoxia.

PMID- 11299215
TI  - Heart rate modulates the slow enhancement of contraction due to sudden left
      ventricular dilation.
AB  - In isovolumic blood-perfused dog hearts, left ventricular developed pressure (DP)
      was recorded while a sudden ventricular dilation was promoted at three heart rate
      (HR) levels: low (L: 52 +/- 1.7 beats/min), intermediate (M: 82 +/- 2.2
      beats/min), and high (H: 117 +/- 3.5 beats/min). DP increased instantaneously
      with chamber expansion (Delta(1)DP), and another continuous increase occurred for
      several minutes (Delta(2)DP). HR elevation did not alter Delta(1)DP (32.8 +/-
      1.6, 33.6 +/- 1.5, and 34.3 +/- 1.2 mmHg for L, M, and H, respectively), even
      though it intensified Delta(2)DP (17.3 +/- 0.9, 20.7 +/- 1.0, and 26.8 +/- 1.2
      mmHg for L, M, and H, respectively), meaning that the treppe phenomenon enhances
      the length dependence of the contraction component related to changes in
      intracellular Ca(2+) concentration. Frequency increments reduced the half time of
      the slow response (82 +/- 3.6, 67 +/- 2.6, and 53 +/- 2.0 s for L, M, and H,
      respectively), while the number of beats included in half time increased (72 +/-
      2.9, 95 +/- 2.9, and 111 +/- 3.2 beats for L, M, and H, respectively). HR
      modulation of the slow response suggests that L-type Ca(2+) channel currents
      and/or the Na(+)/Ca(2+) exchanger plays a relevant role in the stretch-triggered
      Ca(2+) gain when HR increases in the canine heart.

PMID- 11299216
TI  - Importance of PKC and PI3Ks in ethanol-induced contraction of cerebral arterial
      smooth muscle.
AB  - We investigated the relationships of two potential intracellular signaling
      pathways, protein kinase C (PKC) and phosphatidylinositol 3-kinases (PI3Ks), to
      ethanol-induced contractions in cerebral arteries. Ethanol (20-200 mM) induces
      concentration-dependent constriction in isolated canine basilar arteries that is
      inhibited in a concentration-dependent manner by pretreatment of these vessels
      with 10(-9)-10(-3) M Go-6976 (an antagonist selective for PKC-alpha and PKC
      betaI), 10(-10)-10(-4) M bisindolylmaleimide I (a specific antagonist of PKC),
      and 10(-10)-10(-4) M wortmannin or 10(-8)-10(-2) M LY-294002 (selective
      antagonists of PI3Ks). Ethanol-induced increases in intracellular Ca(2+)
      concentration (from approximately 100 to approximately 500 nM) in canine basilar
      smooth muscle cells are also suppressed markedly (approximately 20-70%) in the
      presence of a similar concentration range of Go-6976, bisindolymaleimide I,
      wortmannin, or LY-294002. This study suggests that activation of PKC isoforms and
      PI3Ks appears to be an important signaling pathway in ethanol-induced
      vasoconstriction of cerebral blood vessels.

PMID- 11299217
TI  - Gadolinium attenuates exercise pressor reflex in cats.
AB  - The exercise pressor reflex, which arises from the contraction-induced
      stimulation of group III and IV muscle afferents, is widely believed to be evoked
      by metabolic stimuli signaling a mismatch between blood/oxygen demand and supply
      in the working muscles. Nevertheless, mechanical stimuli may also play a role in
      evoking the exercise pressor reflex. To determine this role, we examined the
      effect of gadolinium, which blocks mechanosensitive channels, on the exercise
      pressor reflex in both decerebrate and alpha-chloralose-anesthetized cats. We
      found that gadolinium (10 mM; 1 ml) injected into the femoral artery
      significantly attenuated the reflex pressor responses to static contraction of
      the triceps surae muscles and to stretch of the calcaneal (Achilles) tendon. In
      contrast, gadolinium had no effect on the reflex pressor response to femoral
      arterial injection of capsaicin (5 microg). In addition, gadolinium significantly
      attenuated the responses of group III muscle afferents, many of which are
      mechanically sensitive, to both static contraction and to tendon stretch.
      Gadolinium, however, had no effect on the responses of group IV muscle afferents,
      many of which are metabolically sensitive, to either static contraction or to
      capsaicin injection. We conclude that mechanical stimuli arising in contracting
      skeletal muscles contribute to the elicitation of the exercise pressor reflex.

PMID- 11299218
TI  - Cerebral blood flow velocity response to induced and spontaneous sudden changes
      in arterial blood pressure.
AB  - The influence of different types of maneuvers that can induce sudden changes of
      arterial blood pressure (ABP) on the cerebral blood flow velocity (CBFV) response
      was studied in 56 normal subjects (mean age 62 yr, range 23-80). ABP was recorded
      in the finger with a Finapres device, and bilateral recordings of CBFV were
      performed with Doppler ultrasound of the middle cerebral arteries. Recordings
      were performed at rest (baseline) and during the thigh cuff test, lower body
      negative pressure, cold pressor test, hand grip, and Valsalva maneuver. From
      baseline recordings, positive and negative spontaneous transients were also
      selected. Stability of PCO2 was monitored with transcutaneous measurements.
      Dynamic autoregulatory index (ARI), impulse, and step responses were obtained for
      1-min segments of data for the eight conditions by fitting a mathematical model
      to the ABP-CBFV baseline and transient data (Aaslid's model) and by the Wiener
      Laguerre moving-average method. Impulse responses were similar for the right- and
      left-side recordings, and their temporal pattern was not influenced by type of
      maneuver. Step responses showed a sudden rise at time 0 and then started to fall
      back to their original level, indicating an active autoregulation. ARI was also
      independent of the type of maneuver, giving an overall mean of 4.7 +/- 2.9 (n =
      602 recordings). Amplitudes of the impulse and step responses, however, were
      significantly influenced by type of maneuver and were highly correlated with the
      resistance-area product before the sudden change in ABP (r = -0.93, P < 0.0004).
      These results suggest that amplitude of the CBFV step response is sensitive to
      the point of operation of the instantaneous ABP-CBFV relationship, which can be
      shifted by different maneuvers. Various degrees of sympathetic nervous system
      activation resulting from different ABP-stimulating maneuvers were not reflected
      by CBFV dynamic autoregulatory responses within the physiological range of ABP.

PMID- 11299219
TI  - Role of endogenous opioids in ischemic preconditioning but not in short-term
      hibernation in pigs.
AB  - Endogenous opioids are involved in ischemic preconditioning (IP) in several
      species. Whether or not opioids are important for IP and short-term myocardial
      hibernation (STMH) in pigs is currently unknown. In 34 enflurane-anesthetized
      pigs, the left anterior descending coronary artery was flow constantly perfused.
      Subendocardial blood flow (Endo), infarct size (IS; percent area at risk), and
      the free energy change of ATP hydrolysis (DeltaG) were determined. After 90-min
      severe ischemia and 120-min reperfusion, IS averaged 28.3 +/- 5.4% (means +/- SE)
      (n = 8; Endo: 0.047 +/- 0.009 ml. min(-1) x g(-1)). IP by 10-min ischemia and 15
      min reperfusion reduced IS to 9.9 +/- 3.8% (P < 0.05, n = 8; Endo: 0.044 +/-
      0.009 ml. min(-1) x g(-1)). After naloxone (1 mg/kg iv followed by 2 microg x kg(
      1) x min(-1)), IS averaged 25.8 +/- 7.0% (n = 6; Endo: 0.039 +/- 0.008 ml x min(
      1) x g(-1)) without and 24.7 +/- 4.7% (n = 6; Endo: 0.044 +/- 0.006 ml x min(-1)
      x g(-1)) with IP. At 5-min moderate ischemia in the presence of naloxone, Endo
      decreased from 0.90 +/- 0.07 to 0.28 +/- 0.03 ml x min(-1) x g(-1)and DeltaG
      decreased from -58.6 +/- 1.0 to -52.6 +/- 0.4 kJ/mol. Prolongation of ischemia to
      90 min did not alter Endo, but DeltaG recovered toward control values (57.7 +/-
      1.1 kJ/mol), and the myocardium remained viable. These responses are identical to
      those of nonnaloxone-treated pigs. Endogenous opioids are involved in IP but not
      in STMH in pigs.

PMID- 11299220
TI  - Pathways of bradykinin degradation in blood and plasma of normotensive and
      hypertensive rats.
AB  - Kinins are vasoactive peptide hormones that can confer protection against the
      development of hypertension. Because their efficacy is greatly influenced by the
      rate of enzymatic degradation, the activities of various kininases in plasma and
      blood of spontaneously hypertensive rats (SHR) were compared with those in
      normotensive Wistar-Kyoto rats (WKY) to identify pathogenic alterations. Either
      plasma or whole blood was incubated with bradykinin (10 microM). Bradykinin and
      kinin metabolites were measured by high-performance liquid chromatography.
      Kininase activities were determined by cumulative inhibition of angiotensin I
      converting enzyme (ACE), carboxypeptidase N (CPN), and aminopeptidase P (APP),
      using selective inhibitors. Plasma of WKY rats degraded bradykinin at a rate of
      13.3 +/- 0.94 micromol x min(-1) x l(-1). The enzymes ACE, APP, and CPN
      represented 92% of this kininase activity, with relative contributions of 52, 25,
      and 16%, respectively. Inclusion of blood cells at physiological concentrations
      did not extend the activities of these plasma kininases further. No differences
      of kinin degradation were found between WKY and SHR. The identical conditions of
      kinin degradation in WKY and SHR suggest no pathogenic role of kininases in the
      SHR model of genetic hypertension.

PMID- 11299221
TI  - Postischemic Na(+)-K(+)-ATPase reactivation is delayed in the absence of
      glycolytic ATP in isolated rat hearts.
AB  - Normalization of intracellular sodium (Na) after postischemic reperfusion depends
      on reactivation of the sarcolemmal Na(+)-K(+)-ATPase. To evaluate the requirement
      of glycolytic ATP for Na(+)-K(+)-ATPase function during postischemic reperfusion,
      5-s time-resolution 23Na NMR was performed in isolated perfused rat hearts.
      During 20 min of ischemia, Na increased approximately twofold. In glucose
      reperfused hearts with or without prior preischemic glycogen depletion, Na
      decreased immediately upon postischemic reperfusion. In glycogen-depleted
      pyruvate-reperfused hearts, however, the decrease of Na was delayed by
      approximately 25 s, and application of the pyruvate dehydrogenase (PDH) activator
      dichloroacetate (DA) did not shorten this delay. After 30 min of reperfusion, Na
      had almost normalized in all groups and contractile recovery was highest in the
      DA-treated hearts. In conclusion, some degree of functional coupling of
      glycolytic ATP and Na(+)-K(+)-ATPase activity exists, but glycolysis is not
      essential for recovery of Na homeostasis and contractility after prolonged
      reperfusion. Furthermore, the delayed Na(+)-K(+)-ATPase reactivation observed in
      pyruvate-reperfused hearts is not due to inhibition of PDH.

PMID- 11299223
TI  - Phenylarsine oxide induces mitochondrial permeability transition,
      hypercontracture, and cardiac cell death.
AB  - The mitochondrial permeability transition (MPT) is implicated in cardiac
      reperfusion/reoxygenation injury. In isolated ventricular myocytes, the
      sulfhydryl (SH) group modifier and MPT inducer phenylarsine oxide (PAO) caused
      MPT, severe hypercontracture, and irreversible membrane injury associated with
      increased cytoplasmic free [Ca(2+)]. Removal of extracellular Ca(2+) or depletion
      of nonmitochondrial Ca(2+) pools did not prevent these effects, whereas the MPT
      inhibitor cyclosporin A was partially protective and the SH-reducing agent
      dithiothreitol fully protective. In permeabilized myocytes, PAO caused
      hypercontracture at much lower free [Ca(2+)] than in its absence. Thus PAO
      induced hypercontracture by both increasing myofibrillar Ca(2+) sensitivity and
      promoting mitochondrial Ca(2+) efflux during MPT. Hypercontracture did not
      directly cause irreversible membrane injury because lactate dehydrogenase (LDH)
      release was not prevented by abolishing hypercontracture with 2,3-butanedione
      monoxime. However, loading myocytes with the membrane-permeable Ca(2+) chelator
      1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester
      (BAPTA-AM) prevented PAO-induced LDH release, thus implicating the PAO-induced
      rise in cytoplasmic [Ca(2+)] as obligatory for irreversible membrane injury. In
      conclusion, PAO induces MPT and enhanced susceptibility to hypercontracture in
      isolated cardiac myocytes, both key features also implicated in cardiac
      reperfusion and reoxygenation injury.

PMID- 11299222
TI  - Angiotensin II AT1 receptors preserve vasodilator reactivity in skeletal muscle
      resistance arteries.
AB  - Resistance arteries (100-150 microm) were isolated from the gracilis muscle of
      normotensive Sprague-Dawley rats placed on a high-salt (HS) diet (4.0% NaCl) for
      3-7 days. Exposure to the HS diet eliminated vascular relaxation in response to
      hypoxia (PO2 reduction to 35-40 Torr) and iloprost, a stable analog of
      prostacyclin. Vasodilator responses were restored in arteries isolated from
      chronically instrumented HS rats receiving a continuous intravenous infusion of
      either angiotensin II (ANG II; 5-6 ng x kg(-1) x min(-1)) or ANG II plus the AT2
      receptor blocker PD-123319 (5 microg x kg(-1) x min(-1)) for 3 days before the
      isolated vessel studies. In contrast, coinfusion of the AT1 receptor blocker
      losartan (20 microg x kg(-1) x min(-1)) or coinfusion of both receptor blockers
      with ANG II eliminated the protective effect of ANG II to restore dilator
      responses to hypoxia and iloprost. Neither a HS diet nor ANG II infusion affected
      the dilation of gracilis arteries in response to direct activation of adenylyl
      cyclase by forskolin, suggesting that the effect of both the HS diet and the ANG
      II on the vasculature is mediated upstream from second messenger systems. These
      findings indicate that the protective effect of ANG II to maintain vasodilator
      reactivity in resistance arteries of rats on a HS diet is mediated via the AT1
      receptor subtype.

PMID- 11299224
TI  - Sp1-mediated downregulation of P2X4 receptor gene transcription in endothelial
      cells exposed to shear stress.
AB  - Endothelial purinoceptors play an important role in vascular responses to
      extracellular adenine nucleotides and hemodynamic forces. Here we report that
      P2X4 purinoceptor expression in human umbilical vein endothelial cells is
      transcriptionally downregulated by fluid shear stress. When human umbilical vein
      endothelial cells were subjected to a laminar shear stress of 15 dyn/cm(2), P2X4
      mRNA levels began to decrease within 1 h and further decreased with time,
      reaching 60% at 24 h. Functional analysis of the 1.9-kb P2X4 5'-promoter
      indicated that a 131-bp segment (-112 to +19 bp relative to the transcription
      start site) containing a consensus binding site for the Sp1 transcription factor
      was critical for the shear stress responsiveness. Mutations of the Sp1 site
      decreased the basal level of transcription and abolished the response of the P2X4
      promoter to shear stress. Electrophoretic mobility shift assays showed a marked
      decrease in binding of Sp1 to the Sp1 consensus element in shear-stressed cells,
      suggesting that Sp1 mediates the shear stress-induced downregulation of P2X4 gene
      transcription.

PMID- 11299225
TI  - Relating myocardial laminar architecture to shear strain and muscle fiber
      orientation.
AB  - Cardiac myofibers are organized into laminar sheets about four cells thick.
      Recently, it has been suggested that these layers coincide with the plane of
      maximum shear during systole. In general, there are two such planes, which are
      oriented at +/-45 degrees to the main principal strain axes. These planes do not
      necessarily contain the fiber axis. In the present study, we explicitly added the
      constraint that the sheet planes should also contain the muscle fiber axis. In a
      mathematical analysis of previously measured three-dimensional transmural
      systolic strain distributions in six dogs, we computed the planes of maximum
      shear, adding the latter constraint by using the also-measured muscle fiber axis.
      Generally, for such planes two solutions were found, suggesting that two
      populations of sheet orientation may exist. The angles at which the predicted
      sheets intersected transmural tissue slices, cut along left ventricular short- or
      long-axis planes, were strikingly similar to experimentally measured values. In
      conclusion, sheets coincide with planes of maximum systolic shear subject to the
      constraint that the muscle fiber axis is contained in this plane. Sheet
      orientation is not a unique function of the transmural location but occurs in two
      distinct populations.

PMID- 11299226
TI  - Regulation of muscle sympathetic nerve activity after bed rest deconditioning.
AB  - Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether
      changes in autonomic function might produce this effect, we developed stimulus
      response curves relating limb vascular resistance, muscle sympathetic nerve
      activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven
      subjects before and after 18 days of -6 degrees head-down bed rest. Both lower
      body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and
      30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic
      tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP
      tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P =
      0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any
      stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest
      deconditioning produced hypovolemia, causing a shift in operating point on the
      stimulus-response curve. The relationship between limb vascular resistance and
      MSNA was not significantly altered after bed rest. We conclude that bed rest
      deconditioning does not alter reflex control of MSNA, but may produce orthostatic
      intolerance through a combination of hypovolemia and cardiac atrophy.

PMID- 11299227
TI  - Effects of VEGF(165) and VEGF(121) on vasculogenesis and angiogenesis in cultured
      embryonic quail hearts.
AB  - It has been documented that hypoxia enhances coronary vasculogenesis and
      angiogenesis in cultured embryonic quail hearts via the upregulation of vascular
      endothelial growth factor (VEGF). In this study, we compared the functions of two
      VEGF splice variants. Ventricles from 6-day-old embryonic quail hearts were
      cultured on three-dimensional collagen gels. Recombinant human VEGF(121) or
      VEGF(165) were added to the culture medium for 48 h, and vascular growth was
      visualized by immunostaining with a quail-specific endothelial cell (EC) marker,
      QH1. VEGF(165) enhanced vascular growth in a dose-dependent manner: 5 ng/ml of
      VEGF(165) slightly increased the number of ECs, 10 ng/ml of VEGF(165) increased
      the incorporation of ECs into tubular structures, and at 20 ng/ml of VEGF(165)
      wider tubes were formed. This pattern plateaued at the 50 ng/ml dose. In
      contrast, VEGF(121) did not enhance either the number of ECs or tube formation at
      these or higher dosages. Combined effects of hypoxia and exogenous VEGF(165) were
      then compared. Tube formation from the heart explants treated with both hypoxia
      and 50 ng/ml of VEGF(165) had a morphology intermediate to those treated with
      hypoxia or VEGF(165) alone. Immunocytochemistry study revealed EC lumenization
      under all culture conditions. However, the addition of VEGF(165) stimulated the
      coalescence of ECs to form larger vessels. We conclude the following: 1)
      VEGF(121) and VEGF(165) induced by hypoxia have different functions on coronary
      vascular growth, 2) unknown factors induced by hypoxia can modify the effect of
      VEGF(165), and 3) EC lumenization observed in the heart explant culture closely
      mimics in vivo coronary vasculogenesis.

PMID- 11299228
TI  - Endothelial function during stimulation of renin-angiotensin system by low-sodium
      diet in humans.
AB  - We examined whether physiological stimulation of the endogenous renin-angiotensin
      system results in impaired endothelium-dependent vasodilatation in forearm
      resistance vessels of healthy subjects and whether this impairment can be
      prevented by angiotensin II type 1 receptor blockade. A low-sodium diet was
      administered to 27 volunteers who were randomized to concomitant treatment with
      losartan (100 mg once daily) or matched placebo in a double-blind fashion.
      Forearm blood flow was assessed by venous occlusion plethysmography at baseline
      and after 5 days. Endothelium-dependent and -independent vasodilation was
      assessed by intra-arterial infusion of methacholine and verapamil, respectively.
      The low-sodium diet resulted in significantly decreased urine sodium excretion
      (placebo: 146 +/- 64 vs. 10 +/- 9 meq/24 h, P < 0.001; losartan: 141 +/- 56 vs.
      14 +/- 14 meq/24 h, P < 0.001) and increased plasma renin activity (placebo: 1.0
      +/- 0.5 vs. 5.0 +/- 2.5 ng x ml(-1) x h(-1), P < 0.001; losartan: 3.8 +/- 7.2 vs.
      19.1 +/- 11.2 ng x ml(-1) x h(-1), P = 0.006) in both the losartan and placebo
      groups. With the baseline study as the reference, the diet intervention was not
      associated with any significant change in endothelium-dependent vasodilation to
      methacholine in either the placebo (P = 0.74) or losartan (P = 0.40) group. We
      conclude that short-term physiological stimulation of the renin-angiotensin
      system does not cause clinically significant endothelial dysfunction. Losartan
      did not influence endothelium-dependent vasodilation in humans with a stimulated
      renin-angiotensin system.

PMID- 11299229
TI  - Nitric oxide modulates arterial baroreflex control of heart rate in conscious
      lambs in an age-dependent manner.
AB  - Experiments were carried out in conscious chronically instrumented lambs aged 1
      (n = 6) and 6 wk (n = 5) to evaluate the arterial baroreflex control of heart
      rate (HR) during postnatal maturation and to investigate any modulatory role of
      endogenously produced nitric oxide (NO). Before and after intravenous
      administration of 20 mg/kg of the L-arginine analog N(G)-nitro-L-arginine methyl
      ester (L-NAME), the arterial baroreflex was assessed by measuring HR responses to
      increases and decreases in systolic arterial pressure achieved by intravenous
      administration of phenylephrine and sodium nitroprusside. The HR range over which
      the baroreflex operates and minimum HR as well as maximum gain were greater at 1
      than at 6 wk of age. These age differences were abolished in the presence of L
      NAME, which decreased the HR range and gain of the arterial baroreflex control of
      HR at 1 but not at 6 wk of age. These data provide new information that age
      dependent effects of the arterial baroreflex appear to result from effects of
      endogenously produced NO.

PMID- 11299230
TI  - PKC-beta is not necessary for cardiac hypertrophy.
AB  - Studies in human and rodent models have shown that activation of protein kinase C
      beta (PKC-beta) is associated with the development of pathological hypertrophy,
      suggesting that ablation of the PKC-beta pathway might prevent or reverse cardiac
      hypertrophy. To explore this, we studied mice with targeted disruption of the PKC
      beta gene (knockout, KO). There were no detectable differences in expression or
      distribution of other PKC isoforms between the KO and control hearts as
      determined by Western blot analysis. Baseline hemodynamics were measured using a
      closed-chest preparation and there were no differences in heart rate and arterial
      or left ventricular pressure. Mice were subjected to two independent hypertrophic
      stimuli: phenylephrine (Phe) at 20 mg x kg(-1) x day(-1) sq infusion for 3 days,
      and aortic banding (AoB) for 7 days. KO animals demonstrated an increase in heart
      weight-to-body weight ratio (Phe, 4.3 +/- 0.6 to 6.1 +/- 0.4; AoB, 4.0 +/- 0.1 to
      5.8 +/- 0.7) as well as ventricular upregulation of atrial natriuretic factor
      mRNA analogous to those seen in control animals. These results demonstrate that
      PKC-beta expression is not necessary for the development of cardiac hypertrophy
      nor does its absence attenuate the hypertrophic response.

PMID- 11299231
TI  - Effects of body temperature during exercise training on myocardial adaptations.
AB  - This study determined the role of body temperature during chronic exercise on
      myocardial stress proteins and antioxidant enzymes as well as functional recovery
      after an ischemic insult. Male Sprague-Dawley rats were exercised for 3, 6, or 9
      wk in a 23 degrees C room (3WK, 6WK, and 9WK, respectively) or in a 4-8 degrees C
      environment with wetted fur (3WKC, 6WKC, and 9WKC, respectively). The colder room
      prevented elevations in core temperature. During weeks 3-9 the animals ran 5
      days/wk up a 6% grade at 20 m/min for 60 min. Myocardial heat shock protein 70
      (HSP 70) increased 12.3-fold (P < 0.05) in 9WK versus sedentary (SED) rats but
      was unchanged in the cold-room runners. Compared with SED rats, alphaB-crystallin
      was 90% higher in 9WKC animals, HSP 90 was 50% higher in 3WKC and 6WKC animals,
      and catalase was 23% higher in 3WK animals (P < 0.05 for all). Cytosolic
      superoxide dismutase increased and mitochondrial SOD decreased (P < 0.05) in 3WK
      and 6WK rats compared with 3WKC and 6WKC rats. Antioxidant enzymes returned to
      SED values in all runners by 9 wk. No differences were observed among any of the
      groups for glucose-regulated protein 75, heme oxygenase-1, or glutathione
      peroxidase. Mechanical recovery of isolated working hearts after 22.5 min of
      global ischemia was enhanced in 9WK (P < 0.05) but not in 9WKC rats. We conclude
      that exercise training results in dynamic changes in cardioprotective proteins
      over time which are influenced by core temperature. In addition, cardioprotection
      resulting from chronic exercise appears to be due to increased HSP 70.

PMID- 11299232
TI  - Effects of soluble TNF receptor treatment on lipopolysaccharide-induced
      myocardial cytokine expression.
AB  - Tumor necrosis factor (TNF)-alpha plays a key role in the pathogenesis of septic
      shock syndrome, and myocardial TNF-alpha expression may contribute to this
      pathophysiology. We examined the myocardial expression of TNF-alpha-related
      cytokines and chemokines in mice exposed to lipopolysaccharide (LPS) and tested
      the effects of anti-TNF therapy on myocardial cytokine expression. Cytokine mRNA
      levels were measured by RNase protection assay, and protein levels in the plasma
      and myocardium were assessed by enzyme-linked immunosorbent assays. LPS (4
      microg/g body wt ip) induced marked cytokine expression, including TNF-alpha,
      interleukin (IL)-1beta, IL-6, and monocyte chemotactic protein (MCP)-1, in both
      the plasma and myocardium. Pretreatment with adenovirus-mediated TNF receptor
      fusion protein (AdTNFR1; 10(9) plaque-forming units iv) decreased plasma cytokine
      levels. In contrast, whereas myocardial IL-1beta expression was also suppressed,
      expression of IL-6 and MCP-1 was not inhibited by AdTNFR1. In summary, anti-TNF
      treatment differentially altered the cytokine expression in the plasma and
      myocardium during endotoxemia. Inability to block myocardial expression of IL-6
      and MCP-1 suggests a possible mechanism for the failure of anti-TNF therapies in
      the treatment of endotoxin shock.

PMID- 11299234
TI  - Systolic axial artery length reduction: an overlooked phenomenon in vivo.
AB  - To demonstrate axial artery motion during the cardiac cycle, the common carotid
      arteries (CCA) of 10 pigs were exposed and equipped with piezoelectric crystals
      sutured onto the artery as axial position detectors. An echo-tracking system was
      used to simultaneously measure the CCA diameter. For each animal, data for
      pressure, length, and diameter were collected at a frequency of 457 Hz. At a mean
      pulse pressure of 33 +/- 8 mmHg, the mean systolodiastolic length difference was
      0.3 +/- 0.01 mm for a mean arterial segment of 11.35 +/- 1.25 mm. Systolic and
      diastolic diameters were 4.1 +/- 0.3 and 3.9 +/- 0.2 mm, respectively. The
      examined CCA segment displayed a mean axial systolic shortening of 2.7%. This
      study clearly demonstrates, for the first time, that the length of a segment of
      the CCA changes during the cardiac cycle and that this movement is inversely
      correlated with pulse pressure. It is also apparent that the segmental axial
      strain is significantly smaller than the diameter variation during the cardiac
      cycle and that the impact of the axial strain for compliance computation should
      be further evaluated.

PMID- 11299233
TI  - Inhibition of hypoxia/reoxygenation-induced apoptosis in metallothionein
      overexpressing cardiomyocytes.
AB  - To study possible mechanisms for metallothionein (MT) inhibition of ischemia
      reperfusion-induced myocardial injury, cardiomyocytes isolated from MT
      overexpressing transgenic neonatal mouse hearts and nontransgenic controls were
      subjected to 4 h of hypoxia (5% CO2-95% N2, glucose-free modified Tyrode's
      solution) followed by 1 h of reoxygenation in MEM + 20% fetal bovine serum (FBS)
      (5% CO2-95% air), and cytochrome c-mediated caspase-3 activation apoptotic
      pathway was determined. Hypoxia/reoxygenation-induced apoptosis was significantly
      suppressed in MT-overexpressing cardiomyocytes, as measured by both terminal
      deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end
      labeling and annexin V-FITC binding. In association with apoptosis, mitochondrial
      cytochrome c release, as determined by Western blot, was observed to occur in
      nontransgenic cardiomyocytes. Correspondingly, caspase-3 was activated as
      determined by laser confocal microscopic examination with the use of FITC
      conjugated antibody against active caspase-3 and by enzymatic assay. The
      activation of this apoptotic pathway was significantly inhibited in MT
      overexpressing cells, as evidenced by both suppression of cytochrome c release
      and inhibition of caspase-3 activation. The results demonstrate that MT
      suppresses hypoxia/reoxygenation-induced cardiomyocyte apoptosis through, at
      least in part, inhibition of cytochrome c-mediated caspase-3 activation.

PMID- 11299235
TI  - Regression by ACE inhibition of arteriosclerotic changes induced by chronic
      blockade of NO synthesis in rats.
AB  - We previously reported that chronic inhibition of nitric oxide (NO) synthesis
      with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces vascular
      inflammation at week 1 and produces subsequent arteriosclerosis at week 4 and
      that cotreatment with an angiotensin-converting enzyme (ACE) inhibitor prevents
      such changes. In the present study, we tested the hypothesis that treatment with
      an ACE inhibitor after development of vascular inflammation could inhibit
      arteriosclerosis in rats. Wistar-Kyoto rats were randomized to four groups: the
      control group received no drugs, the 4wL-NAME group received L-NAME (100 mg x kg(
      1) x day(-1)) for 4 wk, the 1wL + 3wNT group received L-NAME for 1 wk and no
      treatment for the subsequent 3 wk, and the 1wL + 3wACEI group received L-NAME for
      1 wk and the ACE inhibitor imidapril (20 mg x kg(-1) x day(-1)) for the
      subsequent 3 wk. After 4 wk, we observed significant arteriosclerosis of the
      coronary artery (medial thickening and fibrosis) and increased cardiac ACE
      activity in the 1wL + 3wNT group as well as in the 4wL-NAME group, but not in the
      1wL + 3wACEI group. In a separate study, we examined apoptosis formation and
      found that posttreatment with imidapril (20 mg x kg(-1) x day(-1)) or an ANG II
      AT1-receptor antagonist, CS-866 (5 mg x kg(-1) x day(-1)), induced apoptosis (TdT
      mediated nick end-labeling) in monocytes and myofibroblasts appearing in the
      inflammatory lesions associated with a clear degradation in the heart (DNA
      electrophoresis). In conclusion, treatment with the ACE inhibitor after 1 wk of L
      NAME administration inhibited arteriosclerosis by inducing apoptosis in the cells
      with inflammatory lesions in this study, suggesting that increased ANG II
      activity inhibited apoptosis of the cells with inflammatory lesions and thus
      contributed to the development of arteriosclerosis.

PMID- 11299236
TI  - Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R
      injury in transgenic mice.
AB  - To test whether the antiapoptotic protein Bcl-2 prevents apoptosis and injury of
      cardiomyocytes after ischemia-reperfusion (I/R), we generated a line of
      transgenic mice that carried a human Bcl-2 transgene under the control of a mouse
      alpha-myosin heavy chain promoter. High levels of human Bcl-2 transcripts and 26
      kDa Bcl-2 protein were expressed in the hearts of transgenic mice. Functional
      recovery of the transgenic hearts significantly improved when they were perfused
      as Langendorff preparations. This protection was accompanied by a threefold
      decrease in lactate dehydrogenase (LDH) released from the transgenic hearts. The
      transgenic mice were subjected to 50 min of ligation of the left descending
      anterior coronary artery followed by reperfusion. The infarct sizes, expressed as
      a percentage of the area at risk, were significantly smaller in the transgenic
      mice than in the nontransgenic mice (36.6 +/- 5 vs 69.9 +/- 7.3%, respectively).
      In hearts subjected to 30 min of coronary artery occlusion followed by 3 h of
      reperfusion, Bcl-2 transgenic hearts had significantly fewer terminal
      deoxynucleodidyl-transferase nick-end labeling-positive or in situ oligo ligation
      positive myocytes and a less prominent DNA fragmentation pattern. Our results
      demonstrate that overexpression of Bcl-2 renders the heart more resistant to
      apoptosis and I/R injury.

PMID- 11299237
TI  - Preconditioning limits mitochondrial Ca(2+) during ischemia in rat hearts: role
      of K(ATP) channels.
AB  - Prolonged myocardial ischemia results in an increase in intracellular calcium
      concentration ([Ca(2+)]i), which is thought to play a critical role in ischemia
      reperfusion injury. Ischemic preconditioning (PC) improves myocardial function
      during ischemia-reperfusion, a process that may involve opening mitochondrial ATP
      sensitive potassium (K(ATP)) channels. Because pharmacological limitation of
      mitochondrial calcium concentration ([Ca(2+)]m) overload during ischemia
      reperfusion has been shown to improve myocardial function, we hypothesized that
      PC would reduce [Ca(2+)]m during ischemia-reperfusion and that this effect was
      mediated by opening mitochondrial K(ATP) channels. Isolated rat hearts were
      subjected to 25 min of global ischemia and 30 min of reperfusion with or without
      PC in the presence of mitochondrial K(ATP) channel opening (diazoxide, 100
      microM) and blockade [5-hydroxydecanoic acid (5-HD), 100 microM]. Contracture
      during ischemia (end-diastolic pressure) and functional recovery on reperfusion
      (developed pressure) were assessed. Total [Ca(2+)]i and [Ca(2+)]m were measured
      using indo 1 fluorescence. Both PC and diazoxide limited the increase in end
      diastolic pressure and resulted in greater functional recovery after 30 min of
      reperfusion, functional effects that were partially or completely abolished by 5
      HD. PC and diazoxide also significantly limited the increase in [Ca(2+)]m during
      ischemia-reperfusion. In addition, PC lowered [Ca(2+)]i during reperfusion,
      whereas diazoxide paradoxically resulted in increased [Ca(2+)]i during
      reperfusion. There was an inverse linear relationship between [Ca(2+)]m and
      developed pressure during reperfusion. PC limits the ischemia-induced increase in
      mitochondrial, but not total, [Ca(2+)]i, an effect mediated by opening
      mitochondrial K(ATP) channels. These data suggest that the lowering of
      mitochondrial calcium overload is a mechanism of cardioprotection in PC.

PMID- 11299239
TI  - Augmentation of respiratory sinus arrhythmia in response to progressive
      hypercapnia in conscious dogs.
AB  - Respiratory sinus arrhythmia (RSA) may serve to enhance pulmonary gas exchange
      efficiency by matching pulmonary blood flow with lung volume within each
      respiratory cycle. We examined the hypothesis that RSA is augmented as an active
      physiological response to hypercapnia. We measured electrocardiograms and
      arterial blood pressure during progressive hypercapnia in conscious dogs that
      were prepared with a permanent tracheostomy and an implanted blood pressure
      telemetry unit. The intensity of RSA was assessed continuously as the amplitude
      of respiratory fluctuation of heart rate using complex demodulation. In a total
      of 39 runs of hypercapnia in 3 dogs, RSA increased by 38 and 43% of the control
      level when minute ventilation reached 10 and 15 l/min, respectively (P < 0.0001
      for both), and heart rate and mean arterial pressure showed no significant
      change. The increases in RSA were significant even after adjustment for the
      effects of increased tidal volume, respiratory rate, and respiratory fluctuation
      of arterial blood pressure (P < 0.001). These observations indicate that
      increased RSA during hypercapnia is not the consequence of altered autonomic
      balance or respiratory patterns and support the hypothesis that RSA is augmented
      as an active physiological response to hypercapnia.

PMID- 11299238
TI  - Receptor subtypes mediating adenosine-induced dilation of cerebral arterioles.
AB  - The purpose of this study was to investigate the receptor subtypes that mediate
      the dilation of rat intracerebral arterioles elicited by adenosine. Penetrating
      arterioles were isolated from the rat brain, cannulated with the use of a
      micropipette system, and luminally pressurized to 60 mmHg. Both adenosine and the
      A2A receptor-selective agonist CGS-21680 induced dose-dependent vasodilation (
      logEC(50): 6.5 +/- 0.2 and 8.6 +/- 0.3, respectively). However, adenosine, which
      is capable of activating both A2A and A2B receptors, caused a greater maximal
      dilation than CGS-21680. The A2A receptor-selective antagonist ZM-241385 (0.1
      microM) only partially inhibited the dilation induced by adenosine but almost
      completely blocked CGS-21680-induced dilation. Neither 8-cyclopentyl-1,3
      dipropylxanthine (0.1 microM), an A1 receptor-selective antagonist, nor MRS-1191
      (0.1 microM), an A3 receptor-selective antagonist, attenuated adenosine dose
      responses. Moreover, ZM-241385 had no effect on the dilation induced by ATP (10
      microM) or acidic (pH 6.8) buffer. We concluded that the A2A receptor subtype
      mediates adenosine-induced dilation of intracerebral arterioles in the rat brain.
      Furthermore, our results suggest that A2B receptors may also participate in the
      dilation response to adenosine.

PMID- 11299240
TI  - Characterization of PGE2 receptors in fetal and newborn lamb ductus arteriosus.
AB  - Although the role of PGE2 in maintaining ductus arteriosus (DA) patency is well
      established, the specific PGE2 receptor subtype(s) (EP) involved have not been
      clearly identified. We used late gestation fetal and neonatal lambs to study
      developmental regulation of EP receptors. In the fetal DA, radioligand binding
      and RT-PCR assays virtually failed to detect EP1 but detected EP2, EP3D, and EP4
      receptors in equivalent proportions. In the newborn lamb, DA total density was
      one-third of that found in the fetus and only EP2 was detected. Stimulation of
      EP2 and EP4 increased cAMP formation and was associated with DA relaxation.
      Though stimulation of EP3 inhibited cAMP formation, it surprisingly relaxed the
      fetal DA both in vitro and in vivo. This EP3-induced relaxation was specifically
      diminished by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide. In
      conclusion, PGE2 dilates the late gestation fetal DA through pathways that
      involve either cAMP (EP2 and EP4) or K(ATP) channels (EP3). The loss of EP3 and
      EP4 receptors in the newborn DA is consistent with its decreased responsiveness
      to PGE2.

PMID- 11299241
TI  - Nitric oxide reduces energy supply by direct action on the respiratory chain in
      isolated cardiomyocytes.
AB  - To investigate the effect of nitric oxide (NO) on cardiac energy metabolism,
      isolated cardiomyocytes of Wistar rats were incubated in an Oxystat system at a
      constant ambient PO2 (25 mmHg) and oxygen consumption (VO2); free intracellular
      Ca(2+) (fura 2), free cytosolic adenosine [S-adenosylhomocysteine (SAH) method],
      and mitochondrial NADH (autofluorescence) were measured after application of the
      NO donor morpholinosydnonimine (SIN-1). In Na(+)-free medium (contracting
      cardiomyocytes), VO2 increased from 7.9 +/- 1.2 to 26.4 +/- 3.1 nmol x min(-1) x
      mg protein(-1). SIN-1 (100 micromol/l) decreased VO2 in contracting (-21 +/- 3%)
      and in quiescent cells (-24 +/- 7%) by the same extent. Inhibition of VO2 was
      dose dependent (EC(50): 10(-7) mol/l). S-nitroso-N-acetyl-penicillamine, another
      NO donor, also inhibited VO2, whereas SIN-1C (100 micromol/l), the degradation
      product of SIN-1, displayed no inhibitory effect. Intracellular Ca(2+) remained
      unchanged, and inhibition of protein kinases G, A, or C did not antagonize the
      effect of NO. Mitochondrial NADH increased with NO, indicating a reduced flux
      through the respiratory chain. In quiescent but not in contracting
      cardiomyocytes, NO significantly increased adenosine, indicating a reduced energy
      status. These data suggest the following. 1) NO decreases cardiac respiration,
      most likely via direct inhibition of the respiratory chain. 2) Whereas in
      quiescent cardiomyocytes the inhibition of aerobic ATP formation by NO causes
      reduction in energy status, contracting cells are able to compensate for the NO
      induced inhibition of oxidative phosphorylation, maintaining energy status
      constant.

PMID- 11299242
TI  - Hydrogen peroxide stimulates macrophage vascular endothelial growth factor
      release.
AB  - Neutrophils gather at the wound site shortly after trauma and release
      bactericidal reactive oxygen species (ROS) and H2O2 to kill bacteria and prevent
      infection. Macrophages arrive at the wound in response to environmental stimuli,
      phagocytose foreign particles, and release vascular endothelial growth factor
      (VEGF), an angiogenic factor crucial for wound healing. Because oxidants are
      released early in inflammation and have been found to regulate transcription
      factors, we investigated a possible role of H2O2 in VEGF stimulation. Human U937
      macrophages exposed to H2O2 and allowed to recover in H2O2-free medium rapidly
      showed an increase in VEGF mRNA. The H2O2-mediated mRNA increase was dose
      dependent, blocked by catalase, and associated with elevated VEGF in conditioned
      media. The increase in VEGF was also found in primary rat peritoneal macrophages
      and the RAW 264.7 murine macrophage cell line. Transcriptional inhibition with
      actinomycin D revealed no significant difference in mRNA half-life. Transient
      transfections with a 1.6-kb VEGF promoter-luciferase construct (Shima DT, Kuroki
      M, Deutsch U, Ng YS, Adamis AP, and D'Amore PA. J Biol Chem 271: 3877-3883, 1996)
      showed a ninefold stimulation of VEGF gene promoter activity. We concluded that
      H2O2 increases macrophage VEGF through an oxidant induction of VEGF promoter.
      This oxidant stimulation can be mediated by activated neutrophils.

PMID- 11299243
TI  - Anesthetic inhibition in ischemic and nonischemic murine heart: comparison with
      conscious echocardiographic approach.
AB  - It is well known that the level of anesthesia obtained by intraperitoneal
      injection is variable and may alter cardiac function. In this study, we compared
      the effects of different anesthetics on cardiac function with the conscious state
      using high-resolution two-dimensional echocardiography in nonischemic and
      ischemic mice. Eighty-four mice were tested before and after surgery with
      ligation of the coronary artery. All 84 mice were studied in the conscious state
      and under high-dose intraperitoneal anesthesia. Twenty-two of 84 mice were
      studied under low-dose intraperitoneal anesthesia. Another 22 mice were also
      studied under gas anesthesia and spontaneous breathing. Experiments in the
      conscious state were performed by two investigators before the administration of
      anesthesia: one investigator held the animal and the transducer and the other
      operated the ultrasound equipment. Left ventricular systolic function was
      measured, and measurements obtained after surgery were compared with infarcted
      areas assessed by histological staining. Results showed that both high- and low
      dose intraperitoneal anesthesia significantly reduced heart rates and left
      ventricular contractility in both pre- and postsurgical mice as opposed to
      conscious mice (P < 0.01). There were significantly higher correlation
      coefficients between mean fractional area change (FAC) and infarcted area in
      conscious state compared with high-dose intraperitoneal anesthesia (P < 0.05).
      The correlation coefficient between FAC and infarcted area during gas anesthesia
      was also significantly higher compared with high-dose intraperitoneal anesthesia
      (P < 0.05). In conclusion, conscious experiments or the use of gas anesthesia is
      preferred for echocardiographic assessment of cardiac function in mice because
      intraperitoneal injection significantly induces a significant reduction in heart
      rate and left ventricular systolic function.

PMID- 11299244
TI  - NO formation in nucleus tractus solitarii attenuates pressor response evoked by
      skeletal muscle afferents.
AB  - We have previously shown that static muscle contraction induces the expression of
      c-Fos protein in neurons of the nucleus tractus solitarii (NTS) and that some of
      these cells were codistributed with neuronal NADPH-diaphorase [nitric oxide (NO)
      synthase]-positive fibers. In the present study, we sought to determine the role
      of NO in the NTS in mediating the cardiovascular responses elicited by skeletal
      muscle afferent fibers. Static contraction of the triceps surae muscle was
      induced by electrical stimulation of the L7 and S1 ventral roots in anesthetized
      cats. Muscle contraction during microdialysis of artificial extracellular fluid
      increased mean arterial pressure (MAP) and heart rate (HR) 51 +/- 9 mmHg and 18
      +/- 3 beats/min, respectively. Microdialysis of L-arginine (10 mM) into the NTS
      to locally increase NO formation attenuated the increases in MAP (30 +/- 7 mmHg,
      P < 0.05) and HR (14 +/- 2 beats/min, P > 0.05) during contraction. Microdialysis
      of D-arginine (10 mM) did not alter the cardiovascular responses evoked by muscle
      contraction. Microdialysis of N(G)-nitro-L-arginine methyl ester (2 mM) during
      contraction attenuated the effects of L-arginine on the reflex cardiovascular
      responses. These findings demonstrate that an increase in NO formation in the NTS
      attenuates the pressor response to static muscle contraction, indicating that the
      NO system plays a role in mediating the cardiovascular responses to static muscle
      contraction in the NTS.

PMID- 11299245
TI  - Age-related changes in adenosine-mediated relaxation of coronary and aortic
      smooth muscle.
AB  - We tested whether adenosine mediates nitric oxide (NO)-dependent and NO
      independent dilation in coronary and aortic smooth muscle and whether age
      selectively impairs NO-dependent adenosine relaxation. Responses to adenosine and
      the relatively nonselective analog 5'-N-ethylcarboxamidoadenosine (NECA) were
      studied in coronary vessels and aortas from immature (1-2 mo), mature (3-4 mo),
      and moderately aged (12-18 mo) Wistar and Sprague-Dawley rats. Adenosine and NECA
      induced biphasic concentration-dependent coronary vasodilation, with data
      supporting high-sensitivity (pEC(50) = 5.2-5.8) and low-sensitivity (pEC(50) =
      2.3-2.4) adenosine sites. Although sensitivity to adenosine and NECA was
      unaltered by age, response magnitude declined significantly. Treatment with 50
      microM N(G)-nitro-L-arginine methyl ester (L-NAME) markedly inhibited the high
      sensitivity site, although response magnitude still declined with age. Aortic
      sensitivity to adenosine declined with age (pEC(50) = 4.7 +/- 0.2, 3.5 +/- 0.2,
      and 2.9 +/- 0.1 in immature, mature, and moderately aged aortas, respectively),
      and the adenosine receptor transduction maximum also decreased (16.1 +/- 0.8,
      12.9 +/- 0.7, and 9.6 +/- 0.7 mN/mm(2) in immature, mature, and moderately aged
      aortas, respectively). L-NAME decreased aortic sensitivity to adenosine in
      immature and mature tissues but was ineffective in the moderately aged aorta.
      Data collectively indicate that 1) adenosine mediates NO-dependent and NO
      independent coronary and aortic relaxation, 2) maturation and aging reduce NO
      independent and NO-dependent adenosine responses, and 3) the age-related decline
      in aortic response also involves a reduction in the adenosine receptor
      transduction maximum.

PMID- 11299246
TI  - Anatomical and functional characteristics of carotid sinus stimulation in humans.
AB  - Transmission characteristics of pneumatic pressure to the carotid sinus were
      evaluated in 19 subjects at rest and during exercise. Either a percutaneous fluid
      filled (n = 12) or balloon-tipped catheter (n = 7) was placed at the carotid
      bifurcation to record internal transmission of external neck pressure/neck
      suction (NP/NS). Sustained, 5-s pulses, and rapid ramping pulse protocols (+40 to
      -80 Torr) were recorded. Transmission of pressure stimuli was less with the fluid
      filled catheter compared with that of the balloon-tipped catheter (65% vs. 82%
      negative pressure, 83% vs. 89% positive pressure; P < 0.05). Anatomical location
      of the carotid sinus averaged 3.2 cm (left) and 3.6 cm (right) from the gonion of
      the mandible with a range of 0-7.5 cm. Transmission was not altered by exercise
      or Valsalva maneuver, but did vary depending on the position of the carotid sinus
      locus beneath the sealed chamber. These data indicate that transmission of
      external NP/NS was higher than previously recorded in humans, and anatomical
      variation of carotid sinus location and equipment design can affect transmission
      results.

PMID- 11299247
TI  - Adrenergic stimulation of rat resistance arteries affects Ca(2+) sparks, Ca(2+)
      waves, and Ca(2+) oscillations.
AB  - Confocal laser scanning microscopy and fluo 4 were used to visualize local and
      whole cell Ca(2+) transients within individual smooth muscle cells (SMC) of
      intact, pressurized rat mesenteric small arteries during activation of alpha1
      adrenoceptors. A method was developed to record the Ca(2+) transients within
      individual SMC during the changes in arterial diameter. Three distinct types of
      "Ca(2+) signals" were influenced by adrenergic activation (agonist:
      phenylephrine). First, asynchronous Ca(2+) transients were elicited by low levels
      of adrenergic stimulation. These propagated from a point of origin and then
      filled the cell. Second, synchronous, spatially uniform Ca(2+) transients, not
      reported previously, occurred at higher levels of adrenergic stimulation and
      continued for long periods during oscillatory vasomotion. Finally, Ca(2+) sparks
      slowly decreased in frequency of occurrence during exposure to adrenergic
      agonists. Thus adrenergic activation causes a decrease in the frequency of Ca(2+)
      sparks and an increase in the frequency of asynchronous wavelike Ca(2+)
      transients, both of which should tend to decrease arterial diameter. Oscillatory
      vasomotion is associated with spatially uniform synchronous oscillations of
      cellular [Ca(2+)] and may have a different mechanism than the asynchronous,
      propagating Ca(2+) transients.

PMID- 11299248
TI  - Chemical preconditioning with 3-nitropropionic acid in hearts: role of
      mitochondrial K(ATP) channel.
AB  - We investigated the cardioprotective effect of 3-nitropropionic acid (3-NPA), an
      inhibitior of mitochondrial succinate dehydrogenase, and we wanted to show
      whether this protection is mediated by of opening mitochondrial ATP-sensitive
      potassium (K(ATP)) channels. Adult rabbits were treated with either 3-NPA (3
      mg/kg iv) or saline (n = 6 rabbits/group). After 30 min (for early phase) or 24 h
      (for late phase) of the treatment, the animals were subjected to 30 min of
      ischemia and 3 h of reperfusion (ischemia-reperfusion). 5-Hydroxydecanoate (5-HD,
      5 mg/kg iv),the mitochondrial K(ATP) channel blocker, was administered 10 min
      before ischemia-reperfusion in the saline- and 3-NPA-treated rabbits. 3-NPA
      caused a decrease in the infarct size from 27.8 +/- 4.2% in the saline group to
      16.5 +/- 1.0% in the 3-NPA-treated rabbits during early phase and from 30.4 +/-
      4.2% in the saline group to 17.6 +/- 1.05 in the 3-NPA group during delayed phase
      (P < 0.05, % of risk area). The anti-infarct effect of 3-NPA was blocked by 5-HD
      as shown by an increase in infarct size to 33 +/- 2.7% (early phase) and 31 +/-
      2.4% (delayed phase) (P < 0.05 vs. 3-NPA groups). 5-HD had no proischemic effect
      in control animals. Also, 3-NPA had no effect on systemic hemodynamics. We
      conclude that 3-NPA induces long-lasting anti-ischemic effects via opening of
      mitochondrial K(ATP) channels.

PMID- 11299249
TI  - Respiratory mechanics and lung development in the rat from early age to
      adulthood.
AB  - The purpose of the present study was to establish how the dependence of
      respiratory mechanics on lung inflation changes during development. We studied
      seven groups of rats from 10 days to 3 mo of age at five levels of positive end
      expiratory pressure (PEEP) from 0 to 7 hPa (1 hPa = 0.1 kPa approximately 1
      cmH(2)O). At each PEEP level, we measured respiratory system resistance and
      elastance at both 0.9 and 4.8 Hz to partition the mechanical properties into its
      airway and tissue components. Elastance increased more rapidly with PEEP in the
      younger animals, which we interpret as reflecting a more pronounced strain
      stiffening of the younger parenchyma. However, the decrease in airway resistance
      with PEEP was more pronounced in the older animals. Morphometric analysis showed
      that mean tissue density decreased and total alveolar surface area increased with
      age. Our data suggest that the mechanical interdependence between airways and
      parenchyma is weaker in very young animals compared with mature animals. This may
      play a role in the hyperresponsiveness of immaturity.

PMID- 11299250
TI  - Effect of combined recompression and air, oxygen, or heliox breathing on air
      bubbles in rat tissues.
AB  - The fate of bubbles formed in tissues during the ascent from a real or simulated
      air dive and subjected to therapeutic recompression has only been indirectly
      inferred from theoretical modeling and clinical observations. We visually
      followed the resolution of micro air bubbles injected into adipose tissue, spinal
      white matter, muscle, and tendon of anesthetized rats recompressed to and held at
      284 kPa while rats breathed air, oxygen, heliox 80:20, or heliox 50:50. The rats
      underwent a prolonged hyperbaric air exposure before bubble injection and
      recompression. In all tissues, bubbles disappeared faster during breathing of
      oxygen or heliox mixtures than during air breathing. In some of the experiments,
      oxygen breathing caused a transient growth of the bubbles. In spinal white
      matter, heliox 50:50 or oxygen breathing resulted in significantly faster bubble
      resolution than did heliox 80:20 breathing. In conclusion, air bubbles in lipid
      and aqueous tissues shrink and disappear faster during recompression during
      breathing of heliox mixtures or oxygen compared with air breathing. The clinical
      implication of these findings might be that heliox 50:50 is the mixture of choice
      for the treatment of decompression sickness.

PMID- 11299251
TI  - Biventricular cardiac dysfunction after acute massive pulmonary embolism in the
      rat.
AB  - Cardiac dysfunction has been documented in vivo after acute massive pulmonary
      embolism (AMPE). The present study tests whether intrinsic ventricular
      dysfunction occurs in rat hearts isolated after AMPE. AMPE was induced in
      spontaneously breathing ketamine-xylazine-anesthetized rats by thrombus infusion
      until mean arterial blood pressure (MAP) was approximately 40% of basal
      measurement. A hypotensive control group underwent controlled blood withdrawal to
      produce MAP approximately 40% of basal levels. Shams underwent identical surgical
      and anesthesia preparation but without pulmonary embolization. Hearts were
      perfused in isovolumetric mode, and simultaneous right ventricular (RV) and left
      ventricular (LV) pressures were measured. AMPE caused arterial hypotension with
      hypoxemia (PO(2) = 50 +/- 14 Torr), acidemia (pH = 7.26 +/- 0.11), and high
      lactate concentration (6.9 +/- 1.7 mM). Starling curves from both ventricles
      demonstrated that AMPE significantly reduced ex vivo systolic contractile
      function in the RV (P = 0.031) and LV (P = 0.008) compared with both the
      hypotensive control and sham hearts. AMPE did not alter coronary flow or
      compliance in either ventricle. Soluble tumor necrosis factor-alpha decreased in
      the RV (P = 0.043) and LV (P = 0.005) tissue. These data support the hypothesis
      that AMPE produces intrinsic biventricular dysfunction and suggest that arterial
      hypotension is not the principal mechanism of this dysfunction.

PMID- 11299252
TI  - Interpretation of near-infrared spectroscopy signals: a study with a newly
      developed perfused rat brain model.
AB  - Using a newly developed perfused rat brain model, we examined direct effects of
      each change in cerebral blood flow (CBF) and oxygen metabolic rate on cerebral
      hemoglobin oxygenation to interpret near-infrared spectroscopy signals. Changes
      in CBF and total hemoglobin (tHb) were in parallel, although tHb showed no change
      when changes in CBF were small (< or =10%). Increasing CBF caused an increase in
      oxygenated hemoglobin (HbO(2)) and a decrease in deoxygenated hemoglobin (deoxy
      Hb). Decreasing CBF was accompanied by a decrease in HbO(2), whereas changes in
      direction of deoxy-Hb were various. Cerebral blood congestion caused increases in
      HbO(2), deoxy-Hb, and tHb. Administration of pentylenetetrazole without
      increasing the flow rate caused increases in HbO(2) and tHb with a decrease in
      deoxy-Hb. There were no significant differences in venous oxygen saturation
      before vs. during seizure. These results suggest that, in activation studies with
      near-infrared spectroscopy, HbO(2) is the most sensitive indicator of changes in
      CBF, and the direction of changes in deoxy-Hb is determined by the degree of
      changes in venous blood oxygenation and volume.

PMID- 11299253
TI  - Large energetic adaptations of elderly muscle to resistance and endurance
      training.
AB  - This study determined the cellular energetic and structural adaptations of
      elderly muscle to exercise training. Forty male and female subjects (69.2 +/- 0.6
      yr) were assigned to a control group or 6 mo of endurance (ET) or resistance
      training (RT). We used magnetic resonance spectroscopy and imaging to
      characterize energetic properties and size of the quadriceps femoris muscle. The
      phosphocreatine and pH changes during exercise yielded the muscle oxidative
      properties, glycolytic ATP synthesis, and contractile ATP demand. Muscle biopsies
      taken from the same site as the magnetic resonance measurements were used to
      determine myosin heavy chain isoforms, metabolite concentrations, and
      mitochondrial volume densities. The ET group showed changes in all energetic
      pathways: oxidative capacity (+31%), contractile ATP demand (-21%), and
      glycolytic ATP supply (-56%). The RT group had a large increase in oxidative
      capacity (57%). Only the RT group exhibited change in structural properties: a
      rise in mitochondrial volume density (31%) and muscle size (10%). These results
      demonstrate large energetic, but smaller structural, adaptations by elderly
      muscle with exercise training. The rise in oxidative properties with both ET and
      RT suggests that the aerobic pathway is particularly sensitive to exercise
      training in elderly muscle. Thus elderly muscle remains adaptable to chronic
      exercise, with large energetic changes accompanying both ET and RT.

PMID- 11299254
TI  - Mechanical properties of tendon and aponeurosis of human gastrocnemius muscle in
      vivo.
AB  - Load-strain characteristics of tendinous tissues (Achilles tendon and
      aponeurosis) were determined in vivo for human medial gastrocnemius (MG) muscle.
      Seven male subjects exerted isometric plantar flexion torque while the elongation
      of tendinous tissues of MG was determined from the tendinous movements by using
      ultrasonography. The maximal strain of the Achilles tendon and aponeurosis,
      estimated separately from the elongation data, was 5.1 +/- 1.1 and 5.9 +/- 1.6%,
      respectively. There was no significant difference in strain between the Achilles
      tendon and aponeurosis. In addition, no significant difference in strain was
      observed between the proximal and distal regions of the aponeurosis. The results
      indicate that tendinous tissues of the MG are homogeneously stretched along their
      lengths by muscle contraction, which has functional implications for the
      operation of the human MG muscle-tendon unit in vivo.

PMID- 11299255
TI  - Oxygen binding by single red blood cells from the red-eared turtle Trachemys
      scripta.
AB  - Oxygen-binding properties of single red blood cells from the red-eared turtle
      Trachemys scripta were measured by microspectrophotometry to describe the
      variation in oxygen affinity of red blood cells and to gain insight into the
      distribution of functionally different hemoglobins among red blood cells.
      Methodologically, this study represents the first report on the cell-to-cell
      variation in oxygen-binding properties based on oxygen-binding curves of single
      vertebrate red blood cells. The cells differed significantly with respect to
      oxygen affinity. Mean oxygen pressure at half saturation of the cells in a blood
      sample was found to be 20.1 +/- 3.3 (SD) Torr. The distribution of oxygen
      affinities among red blood cells is unimodal, indicating that the two hemoglobins
      found in turtle blood are not segregated in distinct cells. Therefore, the
      functional interaction shown by these hemoglobins in vitro is likely to take
      place in vivo. The considerable variation in oxygen affinity between individual
      red blood cells calls for its incorporation in models of tissue oxygenation.

PMID- 11299256
TI  - Oxidation of [(13)C]glycerol ingested along with glucose during prolonged
      exercise.
AB  - The respective oxidation of glycerol and glucose (0.36 g/kg each) ingested
      simultaneously immediately before exercise (120 min at 68 +/- 2% maximal oxygen
      uptake) was measured in six subjects using (13)C labeling. Indirect respiratory
      calorimetry corrected for protein and glycerol oxidation was used to evaluate the
      effect of glucose + glycerol ingestion on the oxidation of glucose and fat. Over
      the last 80 min of exercise, 10.0 +/- 0.8 g of exogenous glycerol were oxidized
      (43% of the load), while exogenous glucose oxidation was 21% higher (12.1 +/- 0.7
      g or 52% of the load). However, because the energy potential of glycerol is 18%
      higher than that of glucose (4.57 vs. 3.87 kcal/g), the contribution of both
      exogenous substrates to the energy yield was similar (4.0-4.1%). Total glucose
      and fat oxidation were similar in the placebo (144.4 +/- 13.0 and 60.5 +/- 4.2 g,
      respectively) and the glucose + glycerol (135.2 +/- 12.0 and 59.4 +/- 6.5 g,
      respectively) trials, whereas endogenous glucose oxidation was significantly
      lower than in the placebo trial (123.7 +/- 11.7 vs. 144.4 +/- 13.0 g). These
      results indicate that exogenous glycerol can be oxidized during prolonged
      exercise, presumably following conversion into glucose in the liver, although
      direct oxidation in peripheral tissues cannot be ruled out.

PMID- 11299257
TI  - Effect of diaphragm fatigue on neural respiratory drive.
AB  - To test the hypothesis that diaphragm fatigue leads to an increase in neural
      respiratory drive, we measured the esophageal diaphragm electromyogram (EMG)
      during CO(2) rebreathing before and after diaphragm fatigue in six normal
      subjects. The electrode catheter was positioned on the basis of the amplitude and
      polarity of the diaphragm compound muscle action potential recorded
      simultaneously from four pairs of electrodes during bilateral anterior magnetic
      phrenic nerve stimulation (BAMPS) at functional residual capacity. Two minutes of
      maximum isocapnic voluntary ventilation (MIVV) were performed in six subjects to
      induce diaphragm fatigue. A maximal voluntary breathing against an inspiratory
      resistive loading (IRL) was also performed in four subjects. The reduction of
      transdiaphragmatic pressure elicited by BAMPS was 22% (range 13-27%) after 2 min
      of MIVV and was similar, 20% (range 13-26%), after IRL. There was a linear
      relationship between minute ventilation (VE) and the root mean square (RMS) of
      the EMG during CO(2) rebreathing before and after fatigue. The mean slope of the
      linear regression of RMS on VE was similar before and after diaphragm fatigue:
      2.80 +/- 1.31 vs. 3.29 +/- 1.40 for MIVV and 1.51 +/- 0.31 vs 1.55 +/- 0.31 for
      IRL, respectively. We conclude that the esophageal diaphragm EMG can be used to
      assess neural drive and that diaphragm fatigue of the intensity observed in this
      study does not affect respiratory drive.

PMID- 11299258
TI  - Oxygen uptake kinetics during treadmill running in boys and men.
AB  - The purpose of this study was to compare the kinetics of the oxygen uptake
      (VO(2)) response of boys to men during treadmill running using a three-phase
      exponential modeling procedure. Eight boys (11-12 yr) and eight men (21-36 yr)
      completed an incremental treadmill test to determine lactate threshold (LT) and
      maximum VO(2). Subsequently, the subjects exercised for 6 min at two different
      running speeds corresponding to 80% of VO(2) at LT (moderate exercise) and 50% of
      the difference between VO(2) at LT and maximum VO(2) (heavy exercise). For
      moderate exercise, the time constant for the primary response was not
      significantly different between boys [10.2 +/- 1.0 (SE) s] and men (14.7 +/- 2.8
      s). The gain of the primary response was significantly greater in boys than men
      (239.1 +/- 7.5 vs. 167.7 +/- 5.4 ml. kg(-1). km(-1); P < 0.05). For heavy
      exercise, the VO(2) on-kinetics were significantly faster in boys than men
      (primary response time constant = 14.9 +/- 1.1 vs. 19.0 +/- 1.6 s; P < 0.05), and
      the primary gain was significantly greater in boys than men (209.8 +/- 4.3 vs.
      167.2 +/- 4.6 ml. kg(-1). km(-1); P < 0.05). The amplitude of the VO(2) slow
      component was significantly smaller in boys than men (19 +/- 19 vs. 289 +/- 40
      ml/min; P < 0.05). The VO(2) responses at the onset of moderate and heavy
      treadmill exercise are different between boys and men, with a tendency for boys
      to have faster on-kinetics and a greater initial increase in VO(2) for a given
      increase in running speed.

PMID- 11299259
TI  - GABAergic modulation of ventilation and peak oxygen consumption in obese Zucker
      rats.
AB  - Obesity is often associated with a reduced ventilatory response and a decreased
      maximal exercise capacity. GABA is a major inhibitory neurotransmitter in the
      mammalian central nervous system. Altered GABAergic mechanisms have been detected
      in obese Zucker rats and implicated in their hyperphagic response. Whether
      altered GABAergic mechanisms also contribute to regulate ventilation and
      influence exercise capacity in obese Zucker rats is unknown and formed the basis
      of the present study. Eight lean [317 +/- 18 (SD) g] and eight obese (450 +/- 27
      g) Zucker rats were studied at 12 wk of age. Ventilation at rest and ventilation
      during hypoxic (10% O(2)) and hypercapnic (4% CO(2)) challenges were measured by
      the barometric method. Peak O(2) consumption (VO(2 peak)) in response to a
      progressive treadmill test to exhaustion was measured in a metabolic treadmill.
      Ventilation and VO(2 peak) were assessed after administration of equal volumes of
      DMSO (vehicle) and the GABA(A) receptor antagonist bicuculline (1 mg/kg). In lean
      animals, bicuculline administration had no effect on ventilation and VO(2 peak).
      In obese rats, bicuculline administration significantly (P < 0.05) increased
      resting ventilation (465 +/- 53 and 542 +/- 72 ml. kg(-1). min(-1) for control
      and bicuculline, respectively), ventilation during exposure to hypoxia (899 +/-
      148 and 1,038 +/- 83 ml. kg(-1). min(-1) for control and bicuculline,
      respectively), and VO(2 peak) (62 +/- 3.7 and 67 +/- 3.5 ml. kg(-0.75). min(-1)
      for control and bicuculline, respectively). However, in obese Zucker rats,
      ventilation in response to hypercapnia did not change after bicuculline
      administration (608 +/- 96 vs. 580 +/- 69 ml. kg(-1). min(-1)). Our findings
      indicate that endogenous GABA depresses ventilation and limits exercise
      performance in obese Zucker rats.

PMID- 11299260
TI  - Exaggerated muscle mechanoreflex control of reflex renal vasoconstriction in
      heart failure.
AB  - In heart failure (HF) patients, reflex renal vasoconstriction during exercise is
      exaggerated. We hypothesized that muscle mechanoreceptor control of renal
      vasoconstriction is exaggerated in HF. Nineteen HF patients and nineteen controls
      were enrolled in two exercise protocols: 1) low-level rhythmic handgrip
      (mechanoreceptors and central command) and 2) involuntary biceps contractions
      (mechanoreceptors). Renal cortical blood flow was measured by positron emission
      tomography, and renal cortical vascular resistance (RCVR) was calculated. During
      rhythmic handgrip, peak RCVR was greater in HF patients compared with controls
      (37 +/- 1 vs. 27 +/- 1 units; P < 0.01). Change in (Delta) RCVR tended to be
      greater as well but did not reach statistical significance (10 +/- 1 vs. 7 +/-
      0.9 units; P = 0.13). RCVR was returned to baseline at 2-3 min postexercise in
      controls but remained significantly elevated in HF patients. During involuntary
      muscle contractions, peak RCVR was greater in HF patients compared with controls
      (36 +/- 0.7 vs. 24 +/- 0.5 units; P < 0.0001). The Delta RCVR was also
      significantly greater in HF patients compared with controls (6 +/- 1 vs. 4 +/-
      0.6 units; P = 0.05). The data suggest that reflex renal vasoconstriction is
      exaggerated in both magnitude and duration during dynamic exercise in HF
      patients. Given that the exaggerated response was elicited in both the presence
      and absence of central command, it is clear that intact muscle mechanoreceptor
      sensitivity contributes to this augmented reflex renal vasoconstriction.

PMID- 11299261
TI  - Sprint training shortens prolonged action potential duration in postinfarction
      rat myocyte: mechanisms.
AB  - Two electrophysiological manifestations of myocardial infarction (MI)-induced
      myocyte hypertrophy are prolongation of action potential duration (APD) and
      reduction of transient outward current (I(to)) density. Because high-intensity
      sprint training (HIST) ameliorated myocyte hypertrophy and improved myocyte
      Ca(2+) homeostasis and contractility after MI, the present study evaluated
      whether 6-8 wk of HIST would shorten the prolonged APD and improve the depressed
      I(to) in post-MI myocytes. There were no differences in resting membrane
      potential and action potential amplitude (APA) measured in myocytes isolated from
      sham-sedentary (Sed), MI-Sed, and MI-HIST groups. Times required for
      repolarization to 50 and 90% APA were significantly (P < 0.001) prolonged in MI
      Sed myocytes. HIST reduced times required for repolarization to 50 and 90% APA to
      values observed in Sham-Sed myocytes. The fast and slow components of I(to) were
      significantly (P < 0.0001) reduced in MI-Sed myocytes. HIST significantly (P <
      0.001) enhanced the fast and slow components of I(to) in MI myocytes, although
      not to levels observed in Sham-Sed myocytes. There were no significant
      differences in steady-state I(to) inactivation and activation parameters among
      Sham-Sed, MI-Sed, and MI-HIST myocytes. Likewise, recovery from time-dependent
      inactivation was also similar among the three groups. We suggest that
      normalization of APD after MI by HIST may be mediated by restoration of I(to)
      toward normal levels.

PMID- 11299262
TI  - Stress-induced attenuation of the hypercapnic ventilatory response in awake rats.
AB  - To test the hypothesis that stress alters the performance of the respiratory
      control system, we compared the acute (20 min) responses to moderate hypoxia and
      hypercapnia of rats previously subjected to immobilization stress (90 min/day)
      with responses of control animals. Ventilatory measurements were performed on
      awake rats using whole body plethysmography. Under baseline conditions, there
      were no differences in minute ventilation between stressed and unstressed groups.
      Rats previously exposed to immobilization stress had a 45% lower ventilatory
      response to hypercapnia (inspiratory CO(2) fraction = 0.05) than controls. In
      contrast, stress exposure had no statistically significant effect on the
      ventilatory response to hypoxia (inspiratory O(2) fraction = 0.12). Stress
      induced attenuation of the hypercapnic response was associated with reduced tidal
      volume and inspiratory flow increases; the frequency and timing components of the
      response were not different between groups. We conclude that previous exposure to
      a stressful condition that does not constitute a direct challenge to respiratory
      homeostasis can elicit persistent (> or =24 h) functional plasticity in the
      ventilatory control system.

PMID- 11299263
TI  - Simulated microgravity, psychic stress, and immune cells in men: observations
      during 120-day 6 degrees HDT.
AB  - Because 6 degrees head-down tilt (HDT) is an established method to mimic low
      gravity on earth, the aim of the present study was to determine the effects of
      120-day HDT on psychic stress and peripheral blood immune cells in six healthy
      male volunteers. Psychological state was assessed by a current stress test, and
      cortisol was measured in saliva. During HDT, all volunteers developed psychic
      stress, and the diurnal rhythm of cortisol secretion was significantly altered.
      In addition, urine excretion of dopamine and norepinephrine increased. The innate
      part of the immune response was activated, as evidenced by the increase in the
      expression of beta(2)-integrins on polymorphonuclear leukocytes and a rise in the
      number of circulating natural killer (NK) cell lymphocytes. The ratio of T-helper
      to T-cytotoxic and T-suppressor cells decreased, whereas no changes in T and B
      lymphocytes were observed. Plasma levels of interleukin-6 increased significantly
      and returned to basal levels after the end of the HDT period. Thus 6 degrees HDT
      appears to be a valid model to induce psychic stress and neuroendocrine-related
      changes in the immune system, changes that might also be encountered by
      astronauts and cosmonauts during long-duration spaceflights.

PMID- 11299264
TI  - Mechanisms of recruitment in oleic acid-injured lungs.
AB  - Lung recruitment strategies, such as the application of positive end-expiratory
      pressure (PEEP), are thought to protect the lungs from ventilator-associated
      injury by reducing the shear stress associated with the repeated opening of
      collapsed peripheral units. Using the parenchymal marker technique, we measured
      regional lung deformations in 13 oleic acid (OA)-injured dogs during mechanical
      ventilation in different postures. Whereas OA injury caused a marked decrease in
      the oscillation amplitude of dependent lung regions, even the most dependent
      regions maintained normal end-expiratory dimensions. This is because dependent
      lung is flooded as opposed to collapsed. PEEP restored oscillation amplitudes
      only at pressures that raised regional volumes above preinjury levels. Because
      the amount of PEEP necessary to promote dependent lung recruitment increased the
      end-expiratory dimensions of all lung regions (nondependent AND dependent ones)
      compared with their preinjury baseline, the "price" for recruitment is a
      universal increase in parenchymal stress. We conclude that the mechanics of the
      OA-injured lung might be more appropriately viewed as a partial liquid
      ventilation problem and not a shear stress and airway collapse problem and that
      the mechanisms of PEEP-related lung protection might have to be rethought.

PMID- 11299265
TI  - Saline aerosol bolus dispersion. I. The effect of acinar airway alteration.
AB  - We explored the possibility of using a saline aerosol for bolus dispersion
      measurements to detect peripheral airway alterations in smokers. Indexes of
      ventilation inhomogeneity in conductive (S(cond)) and acinar (S(acin)) lung
      zones, as derived from the multiple-breath N(2) washout (Verbanck S, Schuermans
      D, Van Muylem A, Noppen M, Paiva M, and Vincken W, J Appl Physiol 83: 1807-1816,
      1997), were also measured. The saline bolus test consisted of inhaling 60-ml
      saline aerosol boluses to different volumetric lung depths (VLD) in the 1.1 liter
      volume above functional residual capacity. In the never-smoker group (n = 12),
      saline boluses showed bolus dispersion values consistent with normal values
      reported in the literature for 0.5- to 1-microm aerosols. In the smoker group (n
      = 12; 28 +/- 9 pack years, mean +/- SD), significant increases were seen on
      dispersion and skew of the most peripherally inhaled saline boluses (VLD = 800
      ml; P < 0.05) as well as on S(acin) (P = 0.007) with respect to never-smokers.
      Shallow inhaled boluses (VLD = 200 ml) and S(cond) did not reveal any significant
      differences between smokers and never-smokers. This study shows the consistent
      response of two conceptually independent tests, in which both saline aerosol and
      gas-derived indexes point to a heterogeneous distribution of smoking-induced
      structural alterations in the lung periphery.

PMID- 11299266
TI  - Saline aerosol bolus dispersion. II. The effect of conductive airway alteration.
AB  - In a companion study (Verbanck S, Schuermans D, Vincken W, and Paiva M, J Appl
      Physiol 90: 1754-1762, 2001), we investigated whether saline aerosol bolus tests
      could also be used to detect proximal, as opposed to peripheral, airway
      alterations. We studied 10 never-smokers before and after histamine challenge,
      obtaining, for various volumetric lung depths (VLD), saline bolus-derived indexes
      computed by discarding aerosol concentrations below either 50% of the exhaled
      bolus maximum (half-width, H) or below cutoffs ranging from 5 to 25% (standard
      deviation, sigma(5%)-sigma(25%)) and skew (sk(5)-sk(25%)). Multiple-breath N(2)
      washout-derived indexes of conductive (S(cond)) and acinar (S(acin)) ventilation
      inhomogeneity were also determined. After histamine, S(cond) significantly
      increased (P = 0.008) whereas S(acin) remained unaffected, indicating purely
      conductive airway alteration. Consistent with this observation, sk(5%) (or
      sk(25%)) was increased to the same extent at all VLD, and sigma(5%) was increased
      preferentially at low VLD. By contrast, H and sigma(25%) displayed preferential
      increases at high VLD, a pattern similar to that induced by peripheral
      alterations. The present work shows that proximal airway alteration can be
      reliably identified by saline bolus tests only if these include measurements at
      low and high VLD and if bolus dispersion is quantified as a standard deviation
      with a low cutoff.

PMID- 11299267
TI  - Age, sex, race, initial fitness, and response to training: the HERITAGE Family
      Study.
AB  - Effects of age, sex, race, and initial fitness on training responses of maximal
      O(2) uptake (VO(2 max)) are unclear. Data were available on 435 whites and 198
      blacks (287 men and 346 women), aged 17-65 yr, before and after standardized
      cycle ergometer training. Individual responses varied widely, but VO(2 max)
      increased significantly for all groups. Responses by men and women and by blacks
      and whites of all ages varied widely. There was no sex difference for change
      (Delta) in VO(2 max) (ml. kg(-1). min(-1)); women had lower initial values and
      greater relative (%) increases. Blacks began with lower values but had similar
      responses. Older subjects had a lower Delta but a similar percent change.
      Baseline VO(2 max) correlated nonsignificantly with DeltaVO(2 max) but
      significantly with percent change. There were high, medium, and low responders in
      all age groups, both sexes, both races, and all levels of initial fitness. Age,
      sex, race, and initial fitness have little influence on VO(2 max) response to
      standardized training in a large heterogeneous sample of sedentary black and
      white men and women.

PMID- 11299268
TI  - Genomic scan for genes affecting body composition before and after training in
      Caucasians from HERITAGE.
AB  - An autosomal genomewide search for genes related to body composition and its
      changes after a 20-wk endurance-exercise training program has been completed in
      the HERITAGE Family Study. Phenotypes included body mass index (BMI), sum of
      eight skinfold thicknesses, fat mass (FM), fat-free mass, percent body fat
      (%Fat), and plasma leptin levels. A maximum of 364 sib-pairs from 99 Caucasian
      families was studied with the use of 344 markers with single-point and multipoint
      linkage analyses. Evidence of significant linkage was observed for changes in fat
      free mass with the S100A and the insulin-like growth factor I genes (P = 0.0001).
      Suggestive evidence (2.0 < or = Lod < 3.0; 0.0001 < P < or = 0.001) was also
      observed for the changes in FM and %Fat at 1q31 and 18q21-q23, in %Fat with the
      uncoupling protein 2 and 3 genes, and in BMI at 5q14-q21. At baseline, suggestive
      evidence was observed for BMI at 8q23-q24, 10p15, and 14q11; for FM at 14q11; and
      for plasma leptin levels with the low-density lipoprotein receptor gene. This is
      the first genomic scan on genes involved in exercise-training-induced changes in
      body composition that could provide information on the determinants of weight
      loss.

PMID- 11299269
TI  - Detergent inhibits 70-90% of responses to intravenous endotoxin in awake sheep.
AB  - Sheep have reactive pulmonary intravascular macrophages, which are essential for
      the marked pulmonary vascular response to infusions of small quantities of
      endotoxin. In another species with reactive pulmonary intravascular macrophages,
      horses, our laboratory found that an intravenous biosafe detergent, tyloxapol,
      inhibited some systemic and pulmonary responses to endotoxin (Longworth KE, Smith
      BL, Staub NC, Steffey EP, and Serikov V. Am J Vet Res 57: 1063-1066, 1996). We
      determined whether the same detergent would inhibit endotoxin responses in awake
      sheep. In 10 awake, instrumented sheep with chronic lung lymph fistulas, we did a
      control experiment by intravenously infusing 1 microg/kg Escherichia coli
      endotoxin. One week later, we gave 40 micromol/kg tyloxapol intravenously 1-4 h
      before infusing the same dose of endotoxin. In these paired studies, we compared
      pulmonary hemodynamics, lung lymph dynamics, body temperature, circulating
      leukocyte concentrations, and circulating tumor necrosis factor for 6 h. In all
      10 sheep, tyloxapol blocked 80-90% of the pulmonary responses and 70-90% of the
      systemic responses. Tyloxapol is safe, inexpensive, easy to use, and effective
      immediately. It may be a clinically useful approach to contravening many of the
      effects of endotoxemia, in humans as well as animals.

PMID- 11299270
TI  - Carbon dioxide pressure-concentration relationship in arterial and mixed venous
      blood during exercise.
AB  - To calculate cardiac output by the indirect Fick principle, CO(2) concentrations
      (CCO(2)) of mixed venous (Cv(CO(2))) and arterial blood are commonly estimated
      from PCO(2), based on the assumption that the CO(2) pressure-concentration
      relationship (PCO(2)-CCO(2)) is influenced more by changes in Hb concentration
      and blood oxyhemoglobin saturation than by changes in pH. The purpose of the
      study was to measure and assess the relative importance of these variables, both
      in arterial and mixed venous blood, during rest and increasing levels of exercise
      to maximum (Max) in five healthy men. Although the mean mixed venous PCO(2) rose
      from 47 Torr at rest to 59 Torr at the lactic acidosis threshold (LAT) and
      further to 78 Torr at Max, the Cv(CO(2)) rose from 22.8 mM at rest to 25.5 mM at
      LAT but then fell to 23.9 mM at Max. Meanwhile, the mixed venous pH fell from
      7.36 at rest to 7.30 at LAT and to 7.13 at Max. Thus, as work rate increases
      above the LAT, changes in pH, reflecting changes in buffer base, account for the
      major changes in the PCO(2)-CCO(2) relationship, causing Cv(CO(2)) to decrease,
      despite increasing mixed venous PCO(2). Furthermore, whereas the increase in the
      arteriovenous CCO(2) difference of 2.2 mM below LAT is mainly due to the increase
      in Cv(CO(2)), the further increase in the arteriovenous CCO(2) difference of 4.6
      mM above LAT is due to a striking fall in arterial CCO(2) from 21.4 to 15.2 mM.
      We conclude that changes in buffer base and pH dominate the PCO(2)-CCO(2)
      relationship during exercise, with changes in Hb and blood oxyhemoglobin
      saturation exerting much less influence.

PMID- 11299271
TI  - Myosin thick filament lability induced by mechanical strain in airway smooth
      muscle.
AB  - Airway smooth muscle adapts to different lengths with functional changes that
      suggest plastic alterations in the filament lattice. To look for structural
      changes that might be associated with this plasticity, we studied the
      relationship between isometric force generation and myosin thick filament density
      in cell cross sections, measured by electron microscope, after length
      oscillations applied to the relaxed porcine trachealis muscle. Muscles were
      stimulated regularly for 12 s every 5 min. Between two stimulations, the muscles
      were submitted to repeated passive +/- 30% length changes. This caused tetanic
      force and thick-filament density to fall by 21 and 27%, respectively. However, in
      subsequent tetani, both force and filament density recovered to preoscillation
      levels. These findings indicate that thick filaments in airway smooth muscle are
      labile, depolymerization of the myosin filaments can be induced by mechanical
      strain, and repolymerization of the thick filaments underlies force recovery
      after the oscillation. This thick-filament lability would greatly facilitate
      plastic changes of lattice length and explain why airway smooth muscle is able to
      function over a large length range.

PMID- 11299272
TI  - Assessment of respiratory system mechanics by artificial neural networks: an
      exploratory study.
AB  - We evaluated 1) the performance of an artificial neural network (ANN)-based
      technology in assessing the respiratory system resistance (Rrs) and compliance
      (Crs) in a porcine model of acute lung injury and 2) the possibility of using,
      for ANN training, signals coming from an electrical analog (EA) of the lung. Two
      differently experienced ANNs were compared. One ANN (ANN(BIO)) was trained on
      tracings recorded at different time points after the administration of oleic acid
      in 10 anesthetized and paralyzed pigs during constant-flow mechanical
      ventilation. A second ANN (ANN(MOD)) was trained on EA simulations. Both ANNs
      were evaluated prospectively on data coming from four different pigs. Linear
      regression between ANN output and manually computed mechanics showed a regression
      coefficient (R) of 0.98 for both ANNs in assessing Crs. On Rrs, ANN(BIO) showed a
      performance expressed by R = 0.40 and ANN(MOD) by R = 0.61. These results suggest
      that ANNs can learn to assess the respiratory system mechanics during mechanical
      ventilation but that the assessment of resistance and compliance by ANNs may
      require different approaches.

PMID- 11299273
TI  - Plasticity of monkey triceps muscle fibers in microgravity conditions.
AB  - We examined the changes in functional properties of triceps brachii skinned
      fibers from monkeys flown aboard the BION 11 satellite for 14 days and after
      ground-based arm immobilization. The composition of myosin heavy chain (MHC)
      isoforms allowed the identification of pure fibers containing type I (slow) or
      type IIa (fast) MHC isoforms or hybrid fibers coexpressing predominantly slow
      (hybrid slow; HS) or fast (hybrid fast) MHC isoforms. The ratio of HS fibers to
      the whole slow population was higher after flight (28%) than in the control
      population (7%), and the number of fast fibers was increased (up to 86% in flight
      vs. 12% in control). Diameters and maximal tensions of slow fibers were decreased
      after flight. The tension-pCa curves of slow and fast fibers were modified, with
      a decrease in pCa threshold and an increase in steepness. The proper effect of
      microgravity was distinguishable from that of immobilization, which induced less
      marked slow-to-fast transitions (only 59% of fast fibers) and changed the tension
      pCa relationships.

PMID- 11299274
TI  - Inspiratory lung impedance in COPD: effects of PEEP and immediate impact of lung
      volume reduction surgery.
AB  - Frequency-dependent characteristics of lung resistance (RL) and elastance (EL)
      are sensitive to different patterns of airway obstruction. We used an enhanced
      ventilator waveform (EVW) to measure inspiratory RL and EL spectra in ventilated
      patients during thoracic surgery. The EVW delivers an inspiratory flow waveform
      with enhanced spectral excitation from 0.156 to 8.1 Hz. Estimates of the
      coefficients in a trigonometric approximation of the EVW flow and transpulmonary
      pressure inspirations yielded inspiratory RL and EL spectra. We applied the EVW
      in a group with mild obstruction undergoing various thoracoscopic procedures (n =
      6), and another group with severe chronic obstructive pulmonary disease
      undergoing lung volume reduction surgery (n = 8). Measurements were made at
      positive end-expiratory pressure (PEEP) of 0, 3, and 6 cmH(2)O. Inspiratory RL
      was similar in both groups despite marked differences in spirometry. The chronic
      obstructive pulmonary disease patients demonstrated a pronounced frequency
      dependent increase in inspiratory EL consistent with severe heterogeneous
      peripheral airway obstruction. PEEP appears to have beneficial effects by
      reducing peripheral airway resistance. Lung volume reduction surgery resulted in
      increased inspiratory RL and EL at all frequencies and PEEPs, possibly due to
      loss of diseased lung tissue, pulmonary edema, increased mechanical
      heterogeneity, and/or an improvement in airway tethering.

PMID- 11299275
TI  - Evidence that the renin decrease during hypoxia is adenosine mediated in
      conscious dogs.
AB  - This study investigated whether adenosine mediates the decrease in plasma renin
      activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious
      beagle dogs were kept under standardized environmental conditions and received a
      low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the
      dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia
      (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10%
      inspiratory concentration of O(2)). Each of the eight dogs was studied twice in
      randomized order in control and theophylline experiments. In theophylline
      experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously
      during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1).
      h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1))
      and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during
      hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to
      132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/-
      0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II
      decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone
      concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus
      infusion of the adenosine receptor antagonist theophylline inhibited the
      suppression of the renin-angiotensin system during acute hypoxia. The decrease in
      aldosterone occurred independently and is apparently directly related to hypoxia.
      In conclusion, it is likely that adenosine mediates the decrease in PRA during
      acute hypoxia in conscious dogs.

PMID- 11299276
TI  - Osteoblasts respond to pulsatile fluid flow with short-term increases in PGE(2)
      but no change in mineralization.
AB  - Although there is no consensus as to the precise nature of the mechanostimulatory
      signals imparted to the bone cells during remodeling, it has been postulated that
      deformation-induced fluid flow plays a role in the mechanotransduction pathway.
      In vitro, osteoblasts respond to fluid shear stress with an increase in PGE(2)
      production; however, the long-term effects of fluid shear stress on cell
      proliferation and differentiation have not been examined. The goal of this study
      was to apply continuous pulsatile fluid shear stresses to osteoblasts and
      determine whether the initial production of PGE(2) is associated with long-term
      biochemical changes. The acute response of bone cells to a pulsatile fluid shear
      stress (0.6 +/- 0.5 Pa, 3.0 Hz) was characterized by a transient fourfold
      increase in PGE(2) production. After 7 days of static culture (0 dyn/cm(2)) or
      low (0.06 +/- 0.05 Pa, 0.3 Hz) or high (0.6 +/- 0.5 Pa, 3.0 Hz) levels of
      pulsatile fluid shear stress, the bone cells responded with an 83% average
      increase in cell number, but no statistical difference (P > 0.53) between the
      groups was observed. Alkaline phosphatase activity per cell decreased in the
      static cultures but not in the low- or high-flow groups. Mineralization was also
      unaffected by the different levels of applied shear stress. Our results indicate
      that short-term changes in PGE(2) levels caused by pulsatile fluid flow are not
      associated with long-term changes in proliferation or mineralization of bone
      cells.

PMID- 11299277
TI  - beta-Receptor agonist activity of phenylephrine in the human forearm.
AB  - Phenylephrine is generally regarded as a "pure" alpha(1)-agonist. However, after
      treatment of the forearm with the alpha-adrenergic-blocking drug phentolamine,
      brachial artery infusion of phenylephrine can cause transient forearm
      vasodilation. To determine whether this response was beta-receptor mediated,
      phenylephrine, phentolamine, and propranolol were infused into the brachial
      arteries of six healthy volunteers. Forearm vascular conductance (FVC) was also
      calculated and expressed as arbitrary units (units). Infusion of phenylephrine by
      itself (0.5 microg. dl forearm volume(-1). min(-1)) caused a sustained decrease
      (P < 0.05) in FVC from 3.5 +/- 0.7 to 0.9 +/- 0.2 units (P < 0.05). Infusion of
      the alpha-blocker phentolamine increased (P < 0.05) baseline FVC to 5.7 +/- 1.3
      units. Subsequent infusion of phenylephrine after alpha-blockade caused FVC to
      increase (P < 0.05) for ~1 min from 5.7 +/- 1.3 to a peak of 13.1 +/- 1.8 units.
      Propranolol had no effect on baseline flow, and subsequent phenylephrine infusion
      after alpha- and beta-blockade caused a small, but significant, sustained
      decrease in FVC from 5.1 +/- 1.0 to 3.6 +/- 0.8 units. There were no systemic
      effects from the infusions, and saline infusion at the same rate (1-2 ml/min) had
      no forearm vasoconstrictor or dilator effects. These data indicate that in humans
      phenylephrine can exert transient beta(2)-vasodilator activity when its
      predominant alpha-constrictor effects are blocked.

PMID- 11299278
TI  - Reflex control of the cutaneous circulation after acute and chronic local
      capsaicin.
AB  - To investigate whether local activity of capsaicin-sensitive sensory afferents in
      the skin has a modulatory role in the reflex cutaneous vasodilator response to
      hyperthermia in humans, experiments were conducted in two parts. First, low-dose
      topical capsaicin (0.025%) was administered acutely to stimulate local activity
      of these afferents. Second, we temporarily desensitized these nerves in a small
      area of skin using chronic capsaicin treatment (0.075% for 7 days). Each
      intervention was followed by whole body heating using water-perfused suits and
      then by local warming to 42 degrees C for assessment of maximum cutaneous
      vascular conductance. Skin blood flow was measured by laser-Doppler flowmetry and
      divided by mean arterial pressure (Finapres) for assessment of cutaneous vascular
      conductance. Maximum vascular conductance was not influenced by either acute or
      chronic capsaicin treatment (P > 0.10). After acute capsaicin, baseline cutaneous
      vascular conductance was elevated above that at control sites (25.34 +/- 6.25 vs.
      10.57 +/- 2.42%max; P < 0.05). However, internal temperature thresholds for
      vasodilation were not affected by either acute or chronic capsaicin (P > 0.10).
      Furthermore, neither acute (control: 112.74 +/- 36.83 vs. acute capsaicin: 96.92
      +/- 28.92%max/ degrees C; P > 0.10) nor chronic (control: 142.45 +/- 61.89 vs.
      chronic capsaicin: 132.12 +/- 52.60%max/ degrees C; P > 0.10) capsaicin
      administration influenced the sensitivity of the reflex cutaneous vasodilator
      response. We conclude that local activity of capsaicin-sensitive afferents in the
      skin does not modify reflex cutaneous vasodilation during hyperthermia.

PMID- 11299279
TI  - In vivo pressure-flow curve in unilateral rat lung ischemia-reperfusion injury.
AB  - The pressure-flow (P-Q) curve has been widely used in many studies to describe
      the effects of various factors on vascular hemodynamics. It is not clear,
      however, whether unilateral ischemia-reperfusion (IR) alters the P-Q curve of the
      rat lung. In this study, we developed an in vivo P-Q curve using the unilateral
      (left) rat lung before and after IR. Animals were divided into two groups: sham
      and IR. The protocol of the IR group consisted of three periods: baseline,
      ischemia, and reperfusion. P-Q curves were obtained by altering blood flow of the
      left lung during the baseline and the reperfusion periods. The sham group
      received the same operation without IR procedure. An additional group was used to
      compare pulmonary blood flow measured by the microsphere and the ultrasonic
      methods. IR treatment rotated the P-Q curve toward the left, indicating an
      increase in resistance in the left lung. However, this rotation was not found in
      the sham group. A significant correlation (r = 0.87, P < 0.01) between
      percentages of blood flow obtained by the microsphere and ultrasonic methods in
      both right and left lungs was demonstrated. Therefore, we demonstrated a simple
      and useful technique to evaluate changes in the P-Q curves caused by IR in the
      unilateral rat lung model.

PMID- 11299280
TI  - Fall in intracellular PO(2) at the onset of contractions in Xenopus single
      skeletal muscle fibers.
AB  - It remains uncertain whether the delayed onset of mitochondrial respiration on
      initiation of muscle contractions is related to O(2) availability. The purpose of
      this research was to measure the kinetics of the fall in intracellular PO(2) at
      the onset of a contractile work period in rested and previously worked single
      skeletal muscle fibers. Intact single skeletal muscle fibers (n = 11) from
      Xenopus laevis were dissected from the lumbrical muscle, injected with an O(2)
      sensitive probe, mounted in a glass chamber, and perfused with Ringer solution
      (PO(2) = 32 +/- 4 Torr and pH = 7.0) at 20 degrees C. Intracellular PO(2) was
      measured in each fiber during a protocol consisting sequentially of 1-min rest; 3
      min of tetanic contractions (1 contraction/2 s); 5-min rest; and, finally, a
      second 3-min contractile period identical to the first. Maximal force development
      and the fall in force (to 83 +/- 2 vs. 86 +/- 3% of maximal force development) in
      contractile periods 1 and 2, respectively, were not significantly different. The
      time delay (time before intracellular PO(2) began to decrease after the onset of
      contractions) was significantly greater (P < 0.01) in the first contractile
      period (13 +/- 3 s) compared with the second (5 +/- 2 s), as was the time to
      reach 50% of the contractile steady-state intracellular PO(2) (28 +/- 5 vs. 18 +/
      4 s, respectively). In Xenopus single skeletal muscle fibers, 1) the lengthy
      response time for the fall in intracellular PO(2) at the onset of contractions
      suggests that intracellular factors other than O(2) availability determine the on
      kinetics of oxidative phosphorylation and 2) a prior contractile period results
      in more rapid on-kinetics.

PMID- 11299281
TI  - Function of human eccrine sweat glands during dynamic exercise and passive heat
      stress.
AB  - The purpose of this study was to identify the pattern of change in the density of
      activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic
      constant-workload exercise and passive heat stress. Eight male subjects (22.8 +/-
      0.9 yr) exercised at a constant workload (117.5 +/- 4.8 W) and were also
      passively heated by lower-leg immersion into hot water of 42 degrees C under an
      ambient temperature of 25 degrees C and relative humidity of 50%. Esophageal
      temperature, mean skin temperature, sweating rate (SR), and heart rate were
      measured continuously during both trials. The number of ASG was determined every
      4 min after the onset of sweating, whereas SGO was calculated by dividing SR by
      ASG. During both exercise and passive heating, SR increased abruptly during the
      first 8 min after onset of sweating, followed by a slower increase. Similarly for
      both protocols, the number of ASG increased rapidly during the first 8 min after
      the onset of sweating and then ceased to increase further (P > 0.05). Conversely,
      SGO increased linearly throughout both perturbations. Our results suggest that
      changes in forearm sweating rate rely on both ASG and SGO during the initial
      period of exercise and passive heating, whereas further increases in SR are
      dependent on increases in SGO.

PMID- 11299282
TI  - Placental compliance during fetal extracorporeal circulation.
AB  - The fetus requires large amounts of volume when weaning from cardiac bypass. This
      suggests that placental vasculature can act as a large capacitor in the fetal
      circulation. To assess placental compliance of fetal lambs, seven isolated in
      situ lamb placentas were placed on extracorporeal circulation. Umbilical artery
      blood flow was varied from 0 to 350 ml. min(-1). kg fetal wt(-1). Because the
      extracorporeal circuit is a closed system, volume changes in the placenta induced
      by umbilical artery pressure changes were measured from reciprocal volume changes
      in the reservoir. There was a wide range of change in absolute volume of blood
      within the fetal placental compartment (216.4 +/- 29.3 ml). Placental compliance
      was linear over the entire range of pressure changes exerted on the placental
      vasculature (r(2) = 0.83, P = 0.0001). This indicates that the placenta is a
      unique and sensitive capacitor in the fetal circulation. This information is
      important clinically because it establishes that aggressive resuscitation of the
      fetus using volume may be necessary when weaning the fetus from cardiac bypass.

PMID- 11299283
TI  - Oxygen measurements in brain stem slices exposed to normobaric hyperoxia and
      hyperbaric oxygen.
AB  - We previously reported (J Appl Physiol 89: 807-822, 2000) that < or =10 min of
      hyperbaric oxygen (HBO(2); < or = 2,468 Torr) stimulates solitary complex
      neurons. To better define the hyperoxic stimulus, we measured PO(2) in the
      solitary complex of 300-microm-thick rat medullary slices, using polarographic
      carbon fiber microelectrodes, during perfusion with media having PO(2) values
      ranging from 156 to 2,468 Torr. Under control conditions, slices equilibrated
      with 95% O(2) at barometric pressure of 1 atmospheres absolute had minimum PO(2)
      values at their centers (291 +/- 20 Torr) that were approximately 10-fold greater
      than PO(2) values measured in the intact central nervous system (10-34 Torr).
      During HBO(2), PO(2) increased at the center of the slice from 616 +/- 16 to
      1,517 +/- 15 Torr. Tissue oxygen consumption tended to decrease at medium PO(2)
      or = 1,675 Torr to levels not different from values measured at PO(2) found in
      all media in metabolically poisoned slices (2-deoxy-D-glucose and antimycin A).
      We conclude that control medium used in most brain slice studies is hyperoxic at
      normobaric pressure. During HBO(2), slice PO(2) increases to levels that appear
      to reduce metabolism.

PMID- 11299284
TI  - Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse.
AB  - In this paper, we describe the effects of voluntary cage wheel exercise on mouse
      cardiac and skeletal muscle. Inbred male C57/Bl6 mice (age 6-8 wk; n = 12)
      [corrected] ran an average of 4.3 h/24 h, for an average distance of 6.8 km/24 h,
      and at an average speed of 26.4 m/min. A significant increase in the ratio of
      heart mass to body mass (mg/g) was evident after 2 wk of voluntary exercise, and
      cardiac atrial natriuretic factor and brain natriuretic peptide mRNA levels were
      significantly increased in the ventricles after 4 wk of voluntary exercise. A
      significant increase in the percentage of fibers expressing myosin heavy chain
      (MHC) IIa was observed in both the gastrocnemius and the tibialis anterior (TA)
      by 2 wk, and a significant decrease in the percentage of fibers expressing IIb
      MHC was evident in both muscles after 4 wk of voluntary exercise. The TA muscle
      showed a greater increase in the percentage of IIa MHC-expressing fibers than did
      the gastrocnemius muscle (40 and 20%, respectively, compared with 10% for
      nonexercised). Finally, the number of oxidative fibers as revealed by NADH
      tetrazolium reductase histochemical staining was increased in the TA but not the
      gastrocnemius after 4 wk of voluntary exercise. All results are relative to age
      matched mice housed without access to running wheels. Together these data
      demonstrate that voluntary exercise in mice results in cardiac and skeletal
      muscle adaptations consistent with endurance exercise.

PMID- 11299285
TI  - Induction of a fatigue-resistant phenotype in rabbit fast muscle by small daily
      amounts of stimulation.
AB  - We have shown that fatigue resistance can be induced in rabbit tibialis anterior
      (TA) muscles without excessive power loss by continuous stimulation at low
      frequencies, such as 5 Hz, and that the same result is obtained by delivering a
      10-Hz pattern in equal on/off periods. Here we ask whether the same phenotype
      could be produced with daily amounts of stimulation that would be more
      appropriate for clinical use. We stimulated rabbit TA muscles for 6 wk,
      alternating fixed 30-min on periods of stimulation at 10 Hz with off periods of
      different duration. All patterns transformed fast-glycolytic fibers into fast
      oxidative fibers. The muscles had fatigue-resistant properties but retained a
      higher contractile speed and power production than muscles transformed completely
      to the slow-oxidative type. We conclude that in the rabbit as little as one 30
      min period of stimulation in 24 h can result in a substantial increase in the
      resistance of the muscle to fatigue.

PMID- 11299286
TI  - Muscle capillary supply in harbor seals.
AB  - The purpose of this study was to examine muscle capillary supply in harbor seals.
      Locomotory and nonlocomotory muscles of four harbor seals (mass = 17.5-41 kg)
      were glutaraldehyde-perfusion fixed and samples processed for electron microscopy
      and analyzed by morphometry. Capillary-to-fiber number and surface ratios were
      0.81 +/- 0.05 and 0.16 +/- 0.01, respectively. Capillary length and surface area
      per volume of muscle fiber were 1,495 +/- 83 mm/mm(3) and 22.4 +/- 1.6
      mm(2)/mm(3), respectively. In the locomotory muscles, we measured capillary
      length and surface area per volume mitochondria (20.1 +/- 1.7 km/ml and 2,531 +/-
      440 cm(2)/ml). All these values are 1.5-3 times lower than in muscles with
      similar or lower volume densities of mitochondria in dogs of comparable size.
      Compared with terrestrial mammals, the skeletal muscles of harbor seals do not
      match their increased aerobic enzyme capacities and mitochondrial volume
      densities with greater muscle capillary supply. They have a smaller capillary-to
      fiber interface and capillary supply per fiber mitochondrial volume than
      terrestrial mammals of comparable size.

PMID- 11299288
TI  - Intracellular signaling specificity in skeletal muscle in response to different
      modes of exercise.
AB  - The aim of this study was to understand better the specific signaling events
      resulting from different modes of exercise. Three different exercise protocols
      were employed based on their well-characterized, long-term training effects on
      either muscle hypertrophy or endurance phenotypes. Rats were subjected to a
      single bout of either a high-frequency electrical stimulation, a low-frequency
      electrical stimulation, or a running exercise protocol. Postexercise
      intracellular signaling was analyzed in the tibialis anterior and soleus muscles
      at 0, 3, and 6 h. A prolonged increase in p70(S6k) and a transient increase in
      protein kinase B phosphorylation were only observed in response to a growth
      inducing stimulus (e.g., tibialis anterior in high-frequency electrical
      stimulation). In contrast, extracellular regulated kinase and 38-kDa stress
      activated protein kinase were activated in response to all forms of exercise at 0
      h, but only extracellular regulated kinase phosphorylation was found
      significantly elevated at 6 h after running exercise. These results demonstrate
      that different exercise protocols resulted in the selective activation of
      specific intracellular signaling pathways, which may determine the specific
      adaptations induced by different forms of exercise.

PMID- 11299287
TI  - Quantitative electrophoretic analysis of myosin heavy chains in single muscle
      fibers.
AB  - To better understand the molecular basis of the large variation in mechanical
      properties of different fiber types, there has been an intense effort to relate
      the mechanical and energetic properties measured in skinned single fibers to
      those of their constituent cross bridges. There is a significant technical
      obstacle, however, in estimating the number of cross bridges in a single fiber.
      In this study, we have developed a procedure for extraction and quantification of
      myosin heavy chains (MHCs) that permits the routine and direct measurement of the
      myosin content in single muscle fibers. To validate this method, we also compared
      MHC concentration measured in single fibers with the MHC concentration in whole
      fast-twitch (psoas and gracilis) and slow-twitch (soleus) muscles of rabbit. We
      found that the MHC concentration in intact psoas (184 microM) was larger than
      that in soleus (144 microM), as would be expected from their differing
      mitochondrial content and volume of myofibrils. We obtained excellent agreement
      between MHC concentration measured at the single fiber level with that measured
      at the whole muscle level. This not only verifies the efficacy of our procedure
      but also shows that the difference in concentration at the whole muscle level
      simply reflects the concentration differences in the constituent fiber types.
      This new procedure should be of considerable help in future attempts to determine
      kinetic differences in cross bridges from different fiber types.

PMID- 11299289
TI  - Individualized model of human thermoregulation for the simulation of heat stress
      response.
AB  - A population-based dynamic model of human thermoregulation was expanded with
      control equations incorporating the individual person's characteristics (body
      surface area, mass, fat%, maximal O(2) uptake, acclimation). These affect both
      the passive (heat capacity, insulation) and active systems (sweating and skin
      blood flow function). Model parameters were estimated from literature data. Other
      data, collected for the study of individual differences (working at relative or
      absolute workloads in hot-dry [45 degrees C, 20% relative humidity (rh)], warm
      humid [35 degrees C, 80% rh], and cool [21 degrees C, 50% rh] environments), were
      used for validation. The individualized model provides an improved prediction
      [mean core temperature error, -0.21 --> -0.07 degrees C (P < 0.001); mean squared
      error, 0.40 --> 0.16 degrees C, (P < 0.001)]. The magnitude of improvement varies
      substantially with the climate and work type. Relative to an empirical multiple
      regression model derived from these specific data sets, the analytical simulation
      model has between 54 and 89% of its predictive power, except for the cool
      climate, in which this ratio is zero. In conclusion, individualization of the
      model allows improved prediction of heat strain, although a substantial error
      remains.

PMID- 11299290
TI  - A rat lung model of instilled liquid transport in the pulmonary airways.
AB  - When a liquid is instilled in the pulmonary airways during medical therapy, the
      method of instillation affects the liquid distribution throughout the lung. To
      investigate the fluid transport dynamics, exogenous surfactant (Survanta) mixed
      with a radiopaque tracer is instilled into tracheae of vertical, excised rat
      lungs (ventilation 40 breaths/min, 4 ml tidal volume). Two methods are compared:
      For case A, the liquid drains by gravity into the upper airways followed by
      inspiration; for case B, the liquid initially forms a plug in the trachea,
      followed by inspiration. Experiments are continuously recorded using a microfocal
      X-ray source and an image-intensifier, charge-coupled device image train. Video
      images recorded at 30 images/s are digitized and analyzed. Transport dynamics
      during the first few breaths are quantified statistically and follow trends for
      liquid plug propagation theory. A plug of liquid driven by forced air can reach
      alveolar regions within the first few breaths. Homogeneity of distribution
      measured at end inspiration for several breaths demonstrates that case B is twice
      as homogeneous as case A. The formation of a liquid plug in the trachea, before
      inspiration, is important in creating a more uniform liquid distribution
      throughout the lungs.

PMID- 11299291
TI  - Threshold levels of maternal nicotine impairing protective responses of newborn
      rats to intermittent hypoxia.
AB  - Experiments were carried out to determine the threshold level of maternal
      nicotine that impairs protective responses of rat pups to hypoxia. From days 6 or
      7 of gestation, pregnant rats received either vehicle or nicotine (1.50, 3.00, or
      6.00 mg of nicotine tartrate. kg body wt(-1).day(-1)) or vehicle continuously via
      a subcutaneous osmotic minipump. On postnatal days 5 or 6, pups were exposed to a
      single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2) or
      3% CO(2)) and their time to last gasp was determined, or they were exposed to
      intermittent hypoxia and their ability to autoresuscitate from hypoxic-induced
      primary apnea was determined. Perinatal exposure to nicotine did not alter the
      time to last gasp or the total number of gasps when the pups were exposed to a
      single period of hypoxia. The number of successful autoresuscitations on repeated
      exposure to hypoxia was, however, decreased in pups whose dams had received
      either 3.00 or 6.00 mg of nicotine tartrate/kg body wt; these dosage regimens
      produced maternal serum nicotine concentrations of 19 +/- 6 and 35 +/- 8 ng/ml,
      respectively. Thus our experiments define the threshold level of maternal
      nicotine that significantly impairs protective responses of 5- to 6-day-old rat
      pups to intermittent hypoxia such as may occur in human infants during episodes
      of prolonged sleep apnea or positional asphyxia.

PMID- 11299292
TI  - Method for measuring long-term function of muscle-powered implants via
      radiotelemetry.
AB  - Long-term remote monitoring of muscle-powered implants has been made possible
      with development of an adjustable workload that can be remotely monitored to
      assess device function. This technique obviates the need for percutaneous access
      lines and allows test animals to remain untethered, eliminating deleterious
      effects caused by infection, sedation, or animal stress. Hardware components
      include a latex bladder fixed within a hermetically sealed canister, multichannel
      implantable telemetry unit, and subcutaneous access port (for pressure charge
      adjustment). To validate this method, in vitro tests were performed by using a
      third-generation muscle energy converter designed to function as an implantable
      hydraulic pump. Two channels of telemetered pressure data were collected and used
      to calculate six indexes of device function. Calculated parameters were then
      compared with measured values to determine accuracy. Correlation between measured
      and calculated parameters was high in all instances, with most estimates yielding
      errors of <3%. These results demonstrate the utility of this approach and support
      its use as a means to monitor muscle-powered devices during long-term animal
      trials.

PMID- 11299293
TI  - Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms.
AB  - To the majority of the population, recurrent episodes of hypoxia are more likely
      encountered in life than sustained hypoxia. Until recently, much of the
      information on the long-term effects of intermittent hypoxia has come from
      studies on human subjects experiencing chronic recurrent apneas. Recent
      development of animal models of intermittent hypoxia and techniques for exposing
      cell cultures to alternating cycles of hypoxia have led to new information on the
      effects of episodic hypoxia on oxygen-sensing mechanisms in the carotid body
      chemoreceptors and regulation of gene expression. The purpose of this review is
      to highlight some recent studies on the effects of intermittent hypoxia on oxygen
      sensing at the carotid bodies and regulation of gene expression. In a rodent
      model, chronic intermittent hypoxia selectively enhances hypoxic sensitivity of
      the carotid body chemoreceptors. More interestingly, chronic intermittent hypoxia
      also induces a novel form of plasticity in the carotid body, leading to long-term
      facilitation in the sensory discharge. Studies on cell cultures reveal that
      intermittent hypoxia is more potent in activating activator protein-1 and hypoxia
      inducible factor-1 transcription factors than sustained hypoxia. Moreover, some
      evidence suggests that intermittent hypoxia utilizes intracellular signaling
      pathways distinct from sustained hypoxia. Reactive oxygen species generated
      during the reoxygenation phase of intermittent hypoxia might play a key role in
      the effects of intermittent hypoxia on carotid body function and gene expression.
      Global gene profile analysis in cell cultures suggests that certain genes are
      selectively affected by intermittent hypoxia, some upregulated and some
      downregulated. It is suggested that, in intact animals, coordinated gene
      regulation of gene expression might be critical for eliciting phenotypic changes
      in the cardiorespiratory systems in response to intermittent hypoxia. It is hoped
      that future studies will unravel new mechanisms that are unique to intermittent
      hypoxia that may lead to a better understanding of the changes in the
      cardiorespiratory systems and new therapies for diseases associated with chronic
      recurrent episodes of hypoxia.

PMID- 11299294
TI  - Respiratory plasticity following intermittent hypoxia: developmental
      interactions.
AB  - Intermittent hypoxia (IH) is the most frequent form of hypoxia occurring in the
      developing mammal. On one hand, the maturational process of neural, mechanical,
      pulmonary, and sleep state-dependent factors will favor the occurrence of IH
      during early postnatal life. On the other hand, it has also become clear that
      hypoxia, even when short lasting, can modify subsequent respiratory responses to
      hypoxia and induce a variety of genes whose consequences will persist for much
      longer periods than the duration of the hypoxic stimulus itself, i.e., functional
      and adaptive plasticities. The dynamic interactions between the overall duration
      and recurring frequency of IH, the severity of IH, and the level of neural
      maturity at the time of IH will modify the ventilatory, metabolic, and
      cardiovascular responses to hypoxia. We propose that the earlier IH will occur in
      the developmental course the more likely that the physiological responses to an
      ulterior hypoxic challenge will be altered even into adulthood. At this point in
      time, a critical examination of the field would suggest that the short-term
      alterations of the hypoxic ventilatory response (HVR) of the developing mammal to
      IH are qualitatively similar to those of the adult and display a biphasic
      pattern, namely, initial enhancement of the HVR followed by a reduction in HVR.
      However, the short- and long-term effects of IH on the modulation of
      neurotransmitter release, receptor binding and expression, intracellular
      signaling cascades, transcriptional regulation, and gene expression as a function
      of animal maturity are almost completely unknown. Further delineation of such
      complex responses to IH may permit the formulation of interventional strategies
      aiming at reducing the overall vulnerability of the young infant and child to
      apnea and sudden death.

PMID- 11299296
TI  - Phrenic long-term facilitation requires 5-HT receptor activation during but not
      following episodic hypoxia.
AB  - Episodic hypoxia evokes a sustained augmentation of respiratory motor output
      known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment
      with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the
      hypothesis that 5-HT receptor activation is necessary for the induction but not
      maintenance of phrenic LTF. Peak integrated phrenic nerve activity (integralPhr)
      was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial
      PO(2) = 40 +/- 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized,
      vagotomized, paralyzed, and ventilated Sprague-Dawley rats [1) control (n = 11),
      2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45
      min after episodic hypoxia (n = 7 each)]. Ketanserin transiently decreased
      integralPhr, but it returned to baseline levels within 10 min. One hour after
      episodic hypoxia, integralPhr was significantly elevated from baseline in control
      and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin
      pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is
      necessary to initiate (during hypoxia) but not maintain (following hypoxia)
      phrenic LTF.

PMID- 11299297
TI  - Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats.
AB  - Recurrent episodic hypoxia (EH) is a feature of sleep apnea that may be
      responsible for some chronic cardiovascular sequelae such as systemic
      hypertension. Chronic EH (8 h/day for 35 days) causes elevation of diurnal
      resting (unstimulated) mean arterial blood pressure (MAP) in the rat. We used in
      vivo video microscopy to examine arteriolar reactivity in the cremaster muscle of
      male Sprague-Dawley rats subjected to 35 days of EH. Cremaster muscles of EH (n =
      6) and control (n = 6) rats were exposed to varying doses of norepinephrine (NE)
      (10(-10) to 10(-5) M), ACh (10(-9) to 10(-5) M), and endothelin-1 (10(-12) to 10(
      8) M). In a separate experiment, EH (n = 5) and control (n = 6) rats were given
      one dose of a nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl
      ester (L-NAME; 10(-5) M). We also examined endothelial NOS mRNA from the kidneys
      of EH-stimulated and control (unstimulated) rats. Telemetry-monitored EH rats
      showed a 16-mmHg increase in MAP over 35 days, whereas control rats showed no
      change. The response to NE and endothelin-1 were similar for EH and control rats.
      ACh vasodilatation of arterioles in EH rats was significantly attenuated compared
      with that of controls. The degree of vasoconstriction in response to blockade of
      the nitric oxide system by L-NAME was significantly less (83% of baseline
      diameter with L-NAME) for arterioles of EH rats compared with that for controls
      (61% of baseline diameter), implying lower basal resting nitric oxide release in
      the EH rats. Whole kidney mRNA endothelial NOS levels were not different between
      groups. These data support the hypothesis that chronic elevation of blood
      pressure associated with EH involves increased peripheral resistance from
      decreased basal release or production of nitric oxide after 35 days of EH.

PMID- 11299298
TI  - gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia.
AB  - In this review, we present evidence for the role of gamma-aminobutyric acid
      (GABA) neurotransmission in cerebral ischemia-induced neuronal death. While
      glutamate neurotransmission has received widespread attention in this area of
      study, relatively few investigators have focused on the ischemia-induced
      alterations in inhibitory neurotransmission. We present a review of the effects
      of cerebral ischemia on pre and postsynaptic targets within the GABAergic
      synapse. Both in vitro and in vivo models of ischemia have been used to measure
      changes in GABA synthesis, release, reuptake, GABA(A) receptor expression and
      activity. Cellular events generated by ischemia that have been shown to alter
      GABA neurotransmission include changes in the Cl(-) gradient, reduction in ATP,
      increase in intracellular Ca(2+), generation of reactive oxygen species, and
      accumulation of arachidonic acid and eicosanoids. Neuroprotective strategies to
      increase GABA neurotransmission target both sides of the synapse as well, by
      preventing GABA reuptake and metabolism and increasing GABA(A) receptor activity
      with agonists and allosteric modulators. Some of these strategies are quite
      efficacious in animal models of cerebral ischemia, with sedation as the only
      unwanted side-effect. Based on promising animal data, clinical trials with
      GABAergic drugs are in progress for specific types of stroke. This review
      attempts to provide an understanding of the mechanisms by which GABA
      neurotransmission is sensitive to cerebral ischemia. Furthermore, we discuss how
      dysfunction of GABA neurotransmission may contribute to neuronal death and how
      neuronal death can be prevented by GABAergic drugs.

PMID- 11299299
TI  - Adjuvant-induced joint inflammation causes very rapid transcription of beta
      preprotachykinin and alpha-CGRP genes in innervating sensory ganglia.
AB  - Neuropeptides synthesized in dorsal root ganglia (DRG) have been implicated in
      neurogenic inflammation and nociception in experimental and clinical inflammatory
      arthritis. We examined the very early changes in response to adjuvant injection
      in a rat model of unilateral tibio-tarsal joint inflammation and subsequent
      monoarthritis. Within 30 min of adjuvant injection ipsilateral swelling and
      hyperalgesia were apparent, and marked increases in beta-preprotachykinin-A (beta
      PPT-A) and alpha-calcitonin gene-related peptide (CGRP)-encoding mRNAs were
      observed in small-diameter L5 DRG neurones innervating the affected joint. This
      response was augmented by recruitment of additional small-diameter DRG neurones
      expressing beta-PPT-A and CGRP transcripts. The increased mRNA was paralleled by
      initial increases in L5 DRG content of the protein products, substance P and
      calcitonin gene-related peptide. Within 15 min of adjuvant injection there were
      increases in electrical activity in sensory nerves innervating a joint. Blockade
      of this activity prevented the rapid induction in beta-PPT-A and CGRP mRNA
      expression in DRG neurones. Increased expression of heteronuclear (intron E) beta
      PPT-A RNA suggests that increases in beta-PPT-A mRNA levels were, at least in
      part, due to transcription. Pre-treatment with the protein synthesis inhibitor
      cycloheximide had no effect upon the early rise in neuropeptide mRNAS: This and
      the rapid time course of these changes suggest that increased sensory neural
      discharge and activation of a latent modulator of transcription are involved.

PMID- 11299300
TI  - Increases in cortical glutamate concentrations in transgenic amyotrophic lateral
      sclerosis mice are attenuated by creatine supplementation.
AB  - Several lines of evidence implicate excitotoxic mechanisms in the pathogenesis of
      amyotrophic lateral sclerosis (ALS). Transgenic mice with a superoxide dismutase
      mutation (G93A) have been utilized as an animal model of familial ALS (FALS). We
      examined the cortical concentrations of glutamate using in vivo microdialysis and
      in vivo nuclear magnetic resonance (NMR) spectroscopy, and the effect of long
      term creatine supplementation. NMDA-stimulated and Ltrans-pyrrolidine-2,4
      dicarboxylate (LTPD)-induced increases in glutamate were significantly higher in
      G93A mice compared with littermate wild-type mice at 115 days of age. At this
      age, the tissue concentrations of glutamate were also significantly increased as
      measured with NMR spectroscopy. Creatine significantly increased longevity and
      motor performance of the G93A mice, and significantly attenuated the increases in
      glutamate measured with spectroscopy at 75 days of age, but had no effect at 115
      days of age. These results are consistent with impaired glutamate transport in
      G93A transgenic mice. The beneficial effect of creatine may be partially mediated
      by improved function of the glutamate transporter, which has a high demand for
      energy and is susceptible to oxidative stress.

PMID- 11299301
TI  - Activation of nuclear transcription factor kappa B (NF-kappaB) is essential for
      dopamine-induced apoptosis in PC12 cells.
AB  - The etiology of Parkinson's disease is still unknown, though current
      investigations support the notion of the pivotal involvement of oxidative stress
      in the process of neurodegeneration in the substantia nigra (SN). In the present
      study, we investigated the molecular mechanisms underlying cellular response to a
      challenge by dopamine, one of the local oxidative stressors in the SN. Based on
      studies showing that nuclear factor kappa B (NF-kappaB) is activated by oxidative
      stress, we studied the involvement of NF-kappaB in the toxicity of PC12 cells
      following dopamine exposure. We found that dopamine (0.1-0.5 m M) treatment
      increased the phosphorylation of the IkappaB protein, the inhibitory subunit of
      NF-kappaB in the cytoplasm. Immunoblot analysis demonstrated the presence of NF
      kappaB-p65 protein in the nuclear fraction and its disappearance from the
      cytoplasmic fraction after 2 h of dopamine exposure. Dopamine-induced NF-kappaB
      activation was also evidenced by electromobility shift assay using radioactive
      labeled NF-kappaB consensus DNA sequence. Cell-permeable NF-kappaB inhibitor SN
      50 rescued the cells from dopamine-induced apoptosis and showed the importance of
      NF-kappaB activation to the induction of apoptosis. Furthermore, flow cytometry
      assay demonstrated a higher level of translocated NF-kappaB-p65 in the apoptotic
      nuclei than in the unaffected nuclei. In conclusion, our findings suggest that NF
      kappaB activation is essential to dopamine-induced apoptosis in PC12 cells and it
      may be involved in nigral neurodegeneration in patients with Parkinson's disease.

PMID- 11299302
TI  - Human immunodeficiency virus type 1 Tat protein decreases cyclic AMP synthesis in
      rat microglia cultures.
AB  - We have studied the modulation of cyclic AMP (cAMP) accumulation by the human
      immunodeficiency virus type 1 (HIV 1) protein Tat in microglia and astrocyte
      cultures obtained from neonatal rat brain. Pretreatment of microglia with
      recombinant Tat resulted in a dose- and time-dependent decrease of cAMP
      accumulation induced by subsequent exposure to isoproterenol (1 microM). The
      inhibitory action of 100 ng/mL Tat approached 50% after 4 h of preincubation and
      reached a maximum of 70% after 24 h. The Tat-induced time- and dose-dependent
      decrease of cAMP accumulation was observed also when microglial cultures were
      stimulated with the adenylyl cyclase activator forskolin (100 microM). In both
      cases, Tat inhibitory action was 70% reverted by a specific monoclonal anti-Tat
      antibody, but was not prevented either by the phosphodiesterase inhibitor 3
      isobutyl-1-methyl-xantine (100 microM) or by a 16-h pretreatment of microglial
      cultures with the Gi protein inhibitor pertussis toxin (10 ng/mL). All these
      results suggested that the viral protein acts at a step of the cAMP transduction
      pathway other than receptors, G proteins and phosphodiesterases. The target of
      Tat appeared to be adenylyl cyclase, whose activity was markedly reduced (up to
      60%) in membranes prepared from Tat-treated microglial cells, both in basal
      conditions and after stimulation with isoproterenol and forskolin. The inability
      of the competitive inhibitor of nitric oxide synthase N(G)-monometyl- L-arginine
      (20 and 200 microM) to revert Tat action on forskolin-induced cAMP accumulation,
      and of two potent nitric oxide donors, PAPA and DETA (0.1-2 m M), to alter
      forskolin-induced cAMP accumulation, excluded an involvement of nitric oxide in
      Tat-induced adenylyl cyclase inhibition. On the contrary, two inhibitors of
      nuclear factor kappaB activation, N-tosyl-( L)-phenylalanine chloromethyl ketone
      (10 microM) and SN50 (25 microM), markedly prevented the reduction of forskolin
      evoked cAMP accumulation by Tat, suggesting a possible role for this nuclear
      transcriptional factor in the regulation of adenylyl cyclase by Tat in microglia.
      This assumption was strengthened by the ability of lipopolysaccharide (100 ng/mL,
      4 h) to mimic the inhibitory effect of the viral protein. Conversely, astrocyte
      cAMP accumulation was unaffected by the viral protein, as tested at various
      concentrations and time points. Finally, Tat inhibition of microglial adenylyl
      cyclase was not due to non-specific cytotoxicity. As cAMP has been reported to
      exert a neuroprotective role in several in vivo and in vitro models of brain
      pathologies, and microglia is believed to mediate Tat-induced neurotoxicity,
      these results suggest that the ability of Tat to inhibit cAMP synthesis in
      microglia may contribute to neuronal degeneration and cell death associated with
      HIV infection.

PMID- 11299303
TI  - N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its
      relevance to studies of acute brain injury.
AB  - To evaluate the contribution of cellular dysfunction and neuronal loss to brain N
      acetylaspartate (NAA) depletion, NAA was measured in brain tissue by HPLC and UV
      detection in rats subjected to cerebral injury, associated or not with cell
      death. When lesion was induced by intracarotid injection of microspheres, the
      fall in NAA was related to the degree of embolization and to the severity of
      brain oedema. When striatal lesion was induced by local injection of malonate,
      the larger the lesion volume, the higher the NAA depletion. However, reduction of
      brain oedema and striatal lesion by treatment with the lipophilic iron chelator
      dipyridyl (20 mg/kg, 1 h before and every 8 h after embolization) and the
      inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg given 1 h
      before malonate and then every 9 h), respectively, failed to ameliorate the fall
      in NAA. Moreover, after systemic administration of 3-nitropropionic acid, a
      marked reversible fall in NAA striatal content was observed despite the lack of
      tissue necrosis. Overall results show that cellular dysfunction can cause higher
      reductions in NAA level than neuronal loss, thus making of NAA quantification a
      potential tool for visualizing the penumbra area in stroke patients.

PMID- 11299305
TI  - Protein kinase C delta regulates neural cell adhesion molecule polysialylation
      state in the rat brain.
AB  - Polysialylation of neural cell adhesion molecule (NCAM PSA) modulates cell-cell
      homophilic binding and signalling during brain development and the remodelling of
      discrete brain regions in the adult. Following learning, a transient increase in
      the frequency of polysialylated neurones occurs in the dentate gyrus of the
      hippocampal formation, and this has been correlated with the selective retention
      and/or elimination of synapses that are transiently overproduced during memory
      consolidation. We now demonstrate that protein kinase C delta (PKCdelta)
      negatively regulates polysialyltransferase activity in the rat brain during
      development and also in the hippocampus during memory consolidation, where its
      down-regulation in the Golgi membrane fraction coincides with the transient
      increase in NCAM PSA expression. Decreased expression of PKCdelta was also
      observed in the hippocampus of rats reared in a complex environment and this
      directly contrasted the significant increase in frequency of hippocampal
      polysialylated neurones observed in these animals. These effects were isoform
      specific as no change in total PKC enzyme activity was detected during memory
      consolidation and complex environment rearing had no effect on the hippocampal
      expression of PKCalpha, beta, gamma or epsilon. By sequential immunoprecipitation
      and immunoblot analysis, phosphorylation of polysialyltransferase protein(s) was
      (were) demonstrated to occur on both serine and tyrosine residues and this was
      associated with decreased enzyme activity. Moreover, a similar experimental
      approach revealed the degree of PKCdelta co-precipitation with
      polysialyltransferase protein(s) to be inversely correlated with
      polysialyltransferase activity. These findings support in vitro evidence
      indicating PKCdelta to regulate polysialyltransferase activity and NCAM
      polysialylation state.

PMID- 11299304
TI  - Up-regulation of cyclooxygenase-1 in neuroblastoma cell lines by retinoic acid
      and corticosteroids.
AB  - Cyclooxygenases-1 and -2 are both expressed in neuronal cells in vivo. In the
      neuroblastoma cell lines NG108 and N2a, however, only cyclooxygenase-1 was
      detectable. Differentiation of the cells with retinoic acid increased
      cyclooxygenase-1 mRNA and protein expression within 24 and 48 h, respectively. A
      further increase was observed when the cells were concomitantly treated with the
      glucocorticoid dexamethasone (a 2-3-fold increase compared with retinoic acid
      alone). In the absence of retinoic acid, dexamethasone only slightly up-regulated
      cyclooxygenase-1 expression. The inhibitor of protein synthesis cycloheximide
      abrogated the effect of dexamethasone, indicating the involvement of newly
      synthesised proteins. Retinoic acid increased the transcription of cyclooxygenase
      1 mRNA, determined with a luciferase-coupled promoter construct. Dexamethasone
      only slightly augmented cyclooxygenase-1-promoter activity but increased
      cyclooxygenase-1 mRNA stability. Other corticosteroids, hydrocortisone and
      aldosterone, also up-regulated cyclooxygenase-1 whereas neurosteroids or
      oestrogen were ineffective. Up-regulation was mediated primarily by the
      glucocorticoid receptor, because the receptor antagonist RU486 strongly reduced
      the effects of all corticosteroids. This indicated that in NG108 cells, the
      mineralocorticoid aldosterone may bind to the glucocorticoid receptor. Treatment
      of NG108 or N2a cells with corticosteroids did not alter the morphological
      phenotype obtained during differentiation. We thus show that corticosteroids,
      which down-regulate cyclooxygenase expression in most cell types, up-regulate
      cyclooxygenase-1 during neuronal differentiation.

PMID- 11299306
TI  - G protein-coupled receptor kinase 2 mediates mu-opioid receptor desensitization
      in GABAergic neurons of the nucleus raphe magnus.
AB  - Nucleus raphe magnus (NRM) sends the projection to spinal dorsal horn and
      inhibits nociceptive transmission. Analgesic effect produced by mu-opioid
      receptor agonists including morphine partially results from activating the NRM
      spinal cord pathway. It is generally believed that mu-opioid receptor agonists
      disinhibit spinally projecting neurons of the NRM and produce analgesia by
      hyperpolarizing GABAergic interneurons. In the present study, whole-cell patch
      clamp recordings combined with single-cell RT-PCR analysis were used to test the
      hypothesis that DAMGO ([D-Ala(2),N-methyl-Phe(4),Gly-ol(5)]enkephalin), a
      specific mu-opioid receptor agonist, selectively hyperpolarizes NRM neurons
      expressing mRNA of glutamate decarboxylase (GAD(67)). Homologous desensitization
      of mu-opioid receptors in NRM neurons could result in the development of morphine
      induced tolerance. G protein-coupled receptor kinase (GRK) is believed to mediate
      mu-opioid receptor desensitization in vivo. Therefore, we also investigated the
      involvement of GRK in mediating homologous desensitization of DAMAMGO-induced
      electrophysiological effects on NRM neurons by using two experimental strategies.
      First, single-cell RT-PCR assay was used to study the expression of GRK2 and GRK3
      mRNAs in individual DAMGO-responsive NRM neurons. Whole-cell recording was also
      performed with an internal solution containing the synthetic peptide, which
      corresponds to G(betagamma)-binding domain of GRK and inhibits G(betagamma)
      activation of GRK. Our results suggest that DAMGO selectively hyperpolarizes NRM
      GABAergic neurons by opening inwardly rectifying K(+) channels and that GRK2
      mediates short-term homologous desensitization of mu-opioid receptors in NRM
      GABAergic neurons.

PMID- 11299307
TI  - Identification of amino acid residues responsible for the alpha5 subunit binding
      selectivity of L-655,708, a benzodiazepine binding site ligand at the GABA(A)
      receptor.
AB  - L-655,708 is a ligand for the benzodiazepine site of the gamma-aminobutyric acid
      type A (GABA(A)) receptor that exhibits a 100-fold higher affinity for alpha5
      containing receptors compared with alpha1-containing receptors. Molecular biology
      approaches have been used to determine which residues in the alpha5 subunit are
      responsible for this selectivity. Two amino acids have been identified,
      alpha5Thr208 and alpha5Ile215, each of which individually confer approximately 10
      fold binding selectivity for the ligand and which together account for the 100
      fold higher affinity of this ligand at alpha5-containing receptors. L-655,708 is
      a partial inverse agonist at the GABA(A) receptor which exhibited no functional
      selectivity between alpha1- and alpha5-containing receptors and showed no change
      in efficacy at receptors containing alpha1 subunits where amino acids at both of
      the sites had been altered to their alpha5 counterparts (alpha1Ser205-Thr,Val212
      Ile). In addition to determining the binding selectivity of L-655,708, these
      amino acid residues also influence the binding affinities of a number of other
      benzodiazepine (BZ) site ligands. They are thus important elements of the BZ site
      of the GABA(A) receptor, and further delineate a region just N-terminal to the
      first transmembrane domain of the receptor alpha subunit that contributes to this
      binding site.

PMID- 11299308
TI  - Group I metabotropic glutamate receptors are expressed in the chicken retina and
      by cultured retinal amacrine cells.
AB  - Glutamate is well established as an excitatory neurotransmitter in the vertebrate
      retina. Its role as a modulator of retinal function, however, is poorly
      understood. We used immunocytochemistry and calcium imaging techniques to
      investigate whether metabotropic glutamate receptors are expressed in the chicken
      retina and by identified GABAergic amacrine cells in culture. Antibody labeling
      for both metabotropic glutamate receptors 1 and 5 in the retina was consistent
      with their expression by amacrine cells as well as by other retinal cell types.
      In double-labeling experiments, most metabotropic glutamate receptor 1-positive
      cell bodies in the inner nuclear layer also label with anti-GABA antibodies.
      GABAergic amacrine cells in culture were also labeled by metabotropic glutamate
      receptor 1 and 5 antibodies. Metabotropic glutamate receptor agonists elicited
      Ca(2+) elevations in cultured amacrine cells, indicating that these receptors
      were functionally expressed. Cytosolic Ca(2+) elevations were enhanced by
      metabotropic glutamate receptor 1-selective antagonists, suggesting that
      metabotropic glutamate receptor 1 activity might normally inhibit the Ca(2+)
      signaling activity of metabotropic glutamate receptor 5. These results
      demonstrate expression of group I metabotropic glutamate receptors in the avian
      retina and suggest that glutamate released from bipolar cells onto amacrine cells
      might act to modulate the function of these cells.

PMID- 11299310
TI  - Visualizing differences in ligand-induced beta-arrestin-GFP interactions and
      trafficking between three recently characterized G protein-coupled receptors.
AB  - beta-Arrestin 1-GFP or beta-arrestin 2-GFP were coexpressed transiently with G
      protein-coupled receptor kinase 2 within cells stably expressing the orexin-1,
      apelin or melanin-concentrating hormone (MCH), receptors. In response to agonist
      ligands both the orexin-1 and apelin receptors were able to rapidly translocate
      both beta-arrestin 1-GFP and beta-arrestin 2-GFP from cytoplasm to the plasma
      membrane. For the MCH receptor this was only observed for beta-arrestin 2-GFP.
      beta-Arrestin 1-GFP translocated by the apelin receptor remained at the plasma
      membrane during prolonged exposure to ligand even though the receptor became
      internalized. By contrast, for the orexin-1 receptor, internalization of beta
      arrestin 1-GFP within punctate vesicles could be observed for over 60 min in the
      continued presence of agonist. Co-internalization of the orexin-1 receptor was
      observed by monitoring the binding and trafficking of TAMRA-(5- and 6
      carboxytetramethylrhodamine) labelled orexin-A. Subsequent addition of an orexin
      1 receptor antagonist resulted in cessation of incorporation of beta-arrestin 1
      GFP into vesicles at the plasma membrane and a gradual clearance of beta-arrestin
      1-GFP from intracellular vesicles. For the melanin-concentrating hormone receptor
      the bulk of translocated beta-arrestin 2-GFP was maintained at concentrated foci
      close to, or at, the plasma membrane. These results demonstrate very distinct
      features of beta-arrestin-GFP interactions and trafficking for three G protein
      coupled receptors for which the natural ligands have only recently been
      identified and which were thus previously considered as orphan receptors.

PMID- 11299309
TI  - Cell-specific caspase expression by different neuronal phenotypes in transient
      retinal ischemia.
AB  - Emerging evidence supports an important role for caspases in neuronal death
      following ischemia-reperfusion injury. This study assessed whether cell specific
      caspases participate in neuronal degeneration and whether caspase inhibition
      provides neuroprotection following transient retinal ischemia. We utilized a
      model of transient global retinal ischemia. The spatial and temporal pattern of
      the active forms of caspase 1, 2 and 3 expression was determined in retinal
      neurons following ischemic injury. Double-labeling with cell-specific markers
      identified which cells were expressing different caspases. In separate
      experiments, animals received various caspase inhibitors before the induction of
      ischemia. Sixty minutes of ischemia resulted in a delayed, selective neuronal
      death of the inner retinal layers at 7 days. Expression of caspase 1 was not
      detected at any time point. Maximal expression of caspase 2 was found at 24 h
      primarily in the inner nuclear and ganglion cell layers of the retina and
      localized to ganglion and amacrine neurons. Caspase 3 also peaked at 24 h in both
      the inner nuclear and outer nuclear layers and was predominantly expressed in
      photoreceptor cells and to a lesser extent in amacrine neurons. The pan caspase
      inhibitor, Boc-aspartyl fmk, or an antisense oligonucleotide inhibitor of caspase
      2 led to significant histopathologic and functional improvement
      (electroretinogram) at 7 days. No protection was found with the caspase 1
      selective inhibitor, Y-vad fmk. These observations suggest that ischemia
      reperfusion injury activates different caspases depending on the neuronal
      phenotype in the retina and caspase inhibition leads to both histologic
      preservation and functional improvement. Caspases 2 and 3 may act in parallel in
      amacrine neurons following ischemia-reperfusion. These results in the retina may
      shed light on differential caspase specificity in global cerebral ischemia.

PMID- 11299311
TI  - Changes in the expression of G protein-coupled receptor kinases and beta-arrestin
      2 in rat brain during opioid tolerance and supersensitivity.
AB  - We previously demonstrated that chronic treatment of rats with the mu-opioid
      receptor agonist sufentanil induced pharmacological tolerance associated with mu
      opioid receptor desensitization and down-regulation. Administration of the
      calcium channel blocker nimodipine during chronic treatment with sufentanil
      prevented mu-opioid receptor down-regulation, induced down-stream
      supersensitization, and produced supersensitivity to the opioid effects. The
      focus of the present study was to determine a role for G protein-coupled receptor
      kinases (GRKs) and beta-arrestin 2 in agonist-induced mu-opioid receptor
      signalling modulation during chronic opioid tolerance and supersensitivity.
      Tolerance was induced by 7-day chronic infusion of sufentanil (2 microgram/h).
      Supersensitivity was induced by concurrent infusion of sufentanil (2 microgram/h)
      and nimodipine (1 microgram/h) for 7 days. Antinociception was evaluated by the
      tail-flick test. GRK2, GRK3, GRK6 and beta-arrestin 2 immunoreactivity levels
      were determined by western blot in brain cortices. Acute and chronic treatment
      with sufentanil induced analgesic tolerance, associated with up-regulation of
      GRK2, GRK6, and beta-arrestin 2. GRK3 expression only was increased in the
      acutely treated group. When nimodipine was associated to the chronic opioid
      treatment, tolerance expression was prevented, and immunoreactivity levels of
      GRK2, GRK6 and beta-arrestin 2 recovered the control values. These data indicate
      that GRK2, GRK3, GRK6 and beta-arrestin 2 are involved in the short- and long
      term adaptive changes in mu-opioid receptor activity, contributing to tolerance
      development in living animals. These observations also suggest that GRKs and beta
      arrestin 2 could constitute pharmacological targets to prevent opioid tolerance
      development, and to improve the analgesic efficacy of opioid drugs.

PMID- 11299312
TI  - Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine
      receptor: use of a mutant D(2) dopamine receptor that adopts the activated
      conformation.
AB  - The antipsychotic drugs have been shown to be inverse agonists at the D(2)
      dopamine receptor. We have examined the mechanism of this inverse agonism by
      making mutations in residue T343 in the base of the sixth transmembrane spanning
      region of the receptor. T343R, T343S and T343K mutant D(2) dopamine receptors
      were made and the T343R mutant characterized in detail. The T343R mutant D(2)
      dopamine receptor exhibits properties of a receptor that resides more in the
      activated state, namely increased agonist binding affinity (independent of G
      protein coupling and dependent on agonist efficacy), increased agonist potency in
      functional tests (adenylyl cyclase inhibition) and increased inverse agonist
      effects. The binding of agonists to the mutant receptor also shows sensitivity to
      sodium ions, unlike the native receptor, so that isomerization of the receptor to
      its inactive state may be driven by sodium ions. The binding of inverse agonists
      to the receptor is, however, unaffected by the mutation. We conclude that inverse
      agonism at this receptor is not achieved by the inverse agonist binding
      preferentially to the non-activated state of the receptor over the activated
      state. Rather the inverse agonist appears to bind to all forms of the receptor
      but then renders the receptor inactive.

PMID- 11299313
TI  - [(35)S]GTPgammaS autoradiography reveals a wide distribution of G(i/o)-linked ADP
      receptors in the nervous system: close similarities with the platelet P2Y(ADP)
      receptor.
AB  - No G(i)-linked P2Y receptors have been cloned to date but the presence of such
      receptors is thought to be restricted to platelets and certain clonal cell lines.
      Using the functional approach of [(35)S]guanosine 5'-[gamma-thio]-triphosphate
      autoradiography, we uncovered the widespread presence of such receptors in the
      CNS. Under conditions in which the prominent signal due to tonic adenosine
      receptor activity is masked, ADP and ATP stimulated G-protein activity in
      multiple grey and white matter regions. Localization in the grey matter suggests
      inhibitory auto-/heteroreceptor function. In the white matter, activated G
      proteins appeared as 'hot spots' (presumed oligodendrocyte progenitors) with
      scattered distribution along the main fibre tracts. Responses to ATP were
      diminished under conditions that inhibited degradation, suggesting that prior
      conversion to ADP explained agonist action. Uracil nucleotides were ineffective
      but 2-methylthio-ADP activated G proteins approximately 500-fold more potently
      than ADP, although both were similarly degraded. Throughout the brain, ADP
      dependent G-protein activity was reversed by 2-hexylthio-AdoOC(O)Asp(2), a non
      phosphate ATP analogue, whereas selective P2Y(1) receptor antagonists proved
      ineffective. A similar receptor was also disclosed from the adrenal medulla.
      These data witness a hitherto unrecognized abundance of G(i/o)-linked ADP
      receptors in the nervous system. Biochemical and pharmacological behaviour
      suggests striking similarities to the elusive platelet P2Y(ADP) receptor.

PMID- 11299314
TI  - Copper neurotoxicity is dependent on dopamine-mediated copper uptake and one
      electron reduction of aminochrome in a rat substantia nigra neuronal cell line.
AB  - The mechanism of copper (Cu) neurotoxicity was studied in the RCSN-3 neuronal
      dopaminergic cell line, derived from substantia nigra of an adult rat. The
      formation of a Cu-dopamine complex was accompanied by oxidation of dopamine to
      aminochrome. We found that the Cu-dopamine complex mediates the uptake of
      (64)CuSO(4) into the Raul Caviedes substantia nigra-clone 3 (RCSN3) cells, and it
      is inhibited by the addition of excess dopamine (2 m M) (63%, p < 0.001) and
      nomifensine (2 microM) (77%, p < 0.001). Copper sulfate (1 m M) alone was not
      toxic to RCSN-3 cells, but was when combined with dopamine or with dicoumarol
      (95% toxicity; p < 0.001) which inhibits DPNH and TPNH (DT)-diaphorase. Electron
      spin resonance (ESR) spectrum of the 5,5-dimethylpyrroline-N-oxide (DMPO) spin
      trap adducts showed the presence of a C-centered radical when incubating cells
      with dopamine, CuSO(4) and dicoumarol. A decrease in the expression of CuZn
      superoxide dismutase and glutathione peroxidase mRNA was observed when RCSN-3
      cells were treated with CuSO(4), dopamine, or CuSO(4) and dopamine. However, the
      mRNA expression of glutathione peroxidase remained at control levels when the
      cells were treated with CuSO(4), dopamine and dicoumarol. The regulation of
      catalase was different since all the treatments with CuSO(4) increased the
      expression of catalase mRNA. Our results suggest that copper neurotoxicity is
      dependent on: (i) the formation of Cu-dopamine complexes with concomitant
      dopamine oxidation to aminochrome; (ii) dopamine-dependent Cu uptake; and (iii)
      one-electron reduction of aminochrome.

PMID- 11299315
TI  - Developmental expression of metabotropic P2Y(1) and P2Y(2) receptors in freshly
      isolated astrocytes from rat hippocampus.
AB  - There are at least three subtypes of cloned metabotropic P2 receptors linked to
      intracellular Ca(2+) rises in rat brain cells, namely, P2Y(1), P2Y(2) and P2Y(4).
      In this study we explore the subtypes of the metabotropic P2 receptors seen in
      freshly isolated astrocytes (FIAs) from P8-P25 rats. We found by single cell RT
      PCR that in process-bearing FIAs from hippocampi of P8-P12 rats, 31% of the glial
      fibrillary acidic protein (GFAP) mRNA (+) cells expressed P2Y(1) mRNA while only
      5% of the cells tested expressed P2Y(2) mRNA. The expression of P2Y(1) receptor
      mRNA was not changed in FIAs from the hippocampi of P18-P25 rats, but 38% of the
      GFAP mRNA (+) cells in the P18-P25 age group then showed P2Y(2) mRNA. We also
      studied whether the mRNA was expressing functional receptor protein by measuring
      Ca(2+) responses to specific agonists for P2Y(1) and P2Y(2). We found that
      similar proportions of GFAP mRNA (+) FIAs responded to ATP or UTP as showed mRNAs
      for P2Y (1) and P2Y(2,) respectively. Total tissue RNA from P9 and P24 rat
      hippocampus showed a 2.8-fold increase in P2Y(2) mRNA levels from P9 to P24 with
      a decrease in P2Y(1) mRNA. Thus, this study shows a marked up-regulation of mRNA
      for P2Y(2) from 9 to 24 days in rat hippocampus, and some of this increase is
      likely due to the protoplasmic astrocytes which is being translated into
      functional receptor protein in these cells.

PMID- 11299316
TI  - Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene
      expression.
AB  - Chronic cocaine use elicits changes in the pattern of gene expression within
      reinforcement-related, dopaminergic regions. cDNA hybridization arrays were used
      to illuminate cocaine-regulated genes in the nucleus accumbens (NAcc) of non
      human primates (Macaca fascicularis; cynomolgus macaque), treated daily with
      escalating doses of cocaine over one year. Changes seen in mRNA levels by
      hybridization array analysis were confirmed at the level of protein (via specific
      immunoblots). Significantly up-regulated genes included: protein kinase A alpha
      catalytic subunit (PKA(calpha)); cell adhesion tyrosine kinase beta (PYK2);
      mitogen activated protein kinase kinase 1 (MEK1); and beta-catenin. While some of
      these changes exist in previously described cocaine-responsive models, others are
      novel to any model of cocaine use. All of these adaptive responses coexist within
      a signaling scheme that could account for known inductions of genes(e.g. fos and
      jun proteins, and cyclic AMP response element binding protein) previously shown
      to be relevant to cocaine's behavioral actions. The complete data set from this
      experiment has been posted to the newly created Drug and Alcohol Abuse Array Data
      Consortium (http://www.arraydata.org) for mining by the general research
      community.

PMID- 11299317
TI  - Pharmacological characterization of threo-3-methylglutamic acid with excitatory
      amino acid transporters in native and recombinant systems.
AB  - The glutamate analog (+/-) threo-3-methylglutamate (T3MG) has recently been
      reported to inhibit the EAAT2 but not EAAT1 subtype of high-affinity, Na(+)
      dependent excitatory amino acid transporter (EAAT). We have examined the effects
      of T3MG on glutamate-elicited currents mediated by EAATs 1-4 expressed in Xenopus
      oocytes and on the transport of radiolabeled substrate in mammalian cell lines
      expressing EAATs 1-3. T3MG was found to be an inhibitor of EAAT2 and EAAT4 but a
      weak inhibitor of EAAT1 and EAAT3. T3MG competitively inhibited uptake of D
      [(3)H]-aspartate into both cortical and cerebellar synaptosomes with a similar
      potency, consistent with its inhibitory activity on the cloned EAAT2 and EAAT4
      subtypes. In addition, T3MG produced substrate-like currents in oocytes
      expressing EAAT4 but not EAAT2. However, T3MG was unable to elicit heteroexchange
      of preloaded D-[(3)H]-aspartate in cerebellar synaptosomes, inconsistent with the
      behavior of a substrate inhibitor. Finally, T3MG acts as a poor ionotropic
      glutamate receptor agonist in cultured hippocampal neurons: concentrations
      greater than 100 microM T3MG were required to elicit significant NMDA receptor
      mediated currents. Thus, T3MG represents a pharmacological tool for the study of
      not only the predominant EAAT2 subtype but also the EAAT4 subtype highly
      expressed in cerebellum.

PMID- 11299318
TI  - Pitx3 activates mouse tyrosine hydroxylase promoter via a high-affinity binding
      site.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine and
      (nor)adrenaline biosynthesis. Regulation of its gene expression is complex and
      different regulatory mechanisms appear to be operative in various neuronal
      lineages. Pitx3, a homeodomain-containing transcription factor, has been cloned
      from neuronal tissues and, in the CNS, mouse Pitx3 is exclusively expressed in
      midbrain dopaminergic (MesDA) neurons from embryonic day 11 (E11). TH appears in
      these neurons at E11.5, consistent with a putative role of Pitx3 in TH
      transcription. We show that Pitx3 activates the TH promoter through direct
      interaction with a single high-affinity binding site within the promoter and that
      this site is sufficient for Pitx3 responsiveness. In contrast, we did not observe
      an effect of Nurr1, an orphan nuclear receptor essential for normal development
      of MesDA neurons, on TH promoter activity. Pitx3 activation of TH promoter
      activity appears to be cell-dependent suggesting that Pitx3 action may be
      modulated by other(s) regulatory mechanism(s) and factor(s).

PMID- 11299319
TI  - The heat shock response reduces myelin oligodendrocyte glycoprotein-induced
      experimental autoimmune encephalomyelitis in mice.
AB  - The stress response (SR) can block inflammatory gene expression by preventing
      activation of transcription factor nuclear factor-kappa B (NF-kappaB). As
      inflammatory gene expression contributes to the pathogenesis of demyelinating
      diseases, we tested the effects of the SR on the progression of the demyelinating
      disease experimental autoimmune encephalomyelitis (EAE). EAE was actively induced
      in C57BL/6 mice using an encephalitogenic myelin oligodendrocyte glycoprotein
      (MOG(35-55)) peptide. Whole body hyperthermia was used to induce a heat shock
      response (HSR) in immunized mice 2 days after the booster MOG(35-55) peptide
      injection. The HSR reduced the incidence of EAE by 70%, delayed disease onset by
      6 days, and attenuated disease severity. The HSR attenuated leukocyte
      infiltration into CNS assessed by quantitation of perivascular infiltrates, and
      by reduced staining for CD4 and CD25 immunopositive T-cells. T-cell activation,
      assessed by the production of interferon gamma (IFNgamma) in response to MOG(35
      55), was also decreased by the HSR. The HSR reduced inflammatory gene expression
      in the brain that normally occurs during EAE, including the early increase in
      RANTES (regulated on activation of normal T-cell expressed and secreted)
      expression, and the later expression of the inducible form of nitric oxide
      synthase. The early activation of transcription factor NF-kappaB was also blocked
      by the HSR. The finding that the SR reduces inflammation in the brain and the
      clinical severity of EAE opens a novel therapeutic approach for prevention of
      autoimmune diseases.

PMID- 11299320
TI  - Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites
      phosphorylated by coexpression with v-Src.
AB  - The protein tyrosine kinase Src is known to regulate NMDA receptors in native
      neurons. While NR2A, NR2B and NR2D are known to be phosphorylated on tyrosine
      residues, the exact sites have remained unidentified. Immunoprecipitation of NMDA
      receptor subunits followed by western blotting was used to analyze the state of
      tyrosine phosphorylation of recombinant NMDA receptor subunits expressed in
      HEK293 cells. Using antiphosphotyrosine antibody PY20, we find that on expression
      in HEK cells, v-Src and Fyn cause detectable tyrosine phosphorylation only of
      NR2A. Because a stronger signal was produced by the constitutively active v-Src,
      the general region of v-Src phosphorylation was delimited by expression of a
      series of truncation mutants of NR2A. Site-directed mutagenesis on candidate
      sites within the likely region allowed identification of three sites, Y1292,
      Y1325, and Y1387 that account for a significant fraction of the total PY20
      signal. Two of these sites, Y1292 and Y1387, were suggested to control current
      modulation by Src in previous studies of HEK cells expressing NR1/NR2A. One of
      these sites, Y1325, has not yet been evaluated for effects on receptor current. A
      unique tyrosine site, Y1267, was shown not to be a site of detectable
      phosphorylation, in accordance with its Src-independent regulation of receptor
      currents.

PMID- 11299321
TI  - The role of protein kinase C in the regulation of serotonin-2A receptor
      expression.
AB  - We have investigated in C6 glioma cells the involvement of protein kinase C (PKC)
      in the regulation of serotonin-(2A) receptor (5-HT(2A) receptor) expression by
      agonist treatment. Comparison of the time-courses of agonist-induced
      downregulation of receptor number and mRNA indicate that a decrease in the number
      of 5-HT(2A) receptor binding sites in response to serotonin (5-HT) treatment is
      preceded by a decrease in 5-HT(2A) receptor mRNA. This decrease in 5-HT(2A)
      receptor mRNA as a result of agonist exposure was not due to a change in the
      stability or half-life of the transcript. Pretreatment of cells with the PKC
      inhibitor bisindolylmaleimide blocked the decrease in 5-HT(2A) receptor mRNA
      levels, and attenuated the down-regulation of 5-HT(2A) receptor binding sites
      induced by treatment with 5-HT. Experiments performed with the PKC inhibitors
      calphostin C and Go 6976 confirmed that PKC was involved in the regulation of 5
      HT(2A) receptor mRNA by agonist and implicate the conventional subgroup of PKC
      isoforms. Western blot analysis, using isoform-specific anti-PKC antibodies
      showed that under our culture conditions C6 glioma cells express the conventional
      isoforms PKC alpha, PKC gamma, as well as the novel isoforms PKC delta, PKC
      epsilon, and the atypical isoforms PKC lambda and PKC iota. Upon treatment with 5
      HT for 10 min levels of the conventional isoforms PKC alpha and PKC gamma
      increased in the nuclear fraction. Taken together, our results implicate PKC
      alpha and/or PKC gamma in the regulation of 5-HT(2A) mRNA receptor and binding
      sites in response to agonist treatment.

PMID- 11299322
TI  - Enhanced neuronal protection from oxidative stress by coculture with glutamic
      acid decarboxylase-expressing astrocytes.
AB  - Astrocytes expressing glutamic acid decarboxylase GAD67 directed by the glial
      fibrillary acidic protein promoter were shown to provide enhanced protection of
      PC12 cells from H(2)O(2) treatment and serum deprivation in the presence of
      glutamate. In addition, they protected non-differentiated, but not
      differentiated, embryonic rat cortical neurons from glutamate toxicity. Glutamic
      acid decarboxylase (GAD)-expressing astrocytes showed increased glutathione
      synthesis and release compared to control astrocytes. These changes were due to
      GAD transgene expression, as transient expression of a GAD antisense plasmid
      resulted in partial suppression of the increase in glutathione release. In
      addition to the previously demonstrated increases in NADH and ATP levels and
      lactate release, GAD-expressing astrocytes show increased antioxidant activity,
      explaining their ability to protect neurons from various injuries.

PMID- 11299323
TI  - 5-HT(1A) receptor mutant mice exhibit enhanced tonic, stress-induced and
      fluoxetine-induced serotonergic neurotransmission.
AB  - Mutant mice that lack serotonin(1A) receptors exhibit enhanced anxiety-related
      behaviors, a phenotype that is hypothesized to result from impaired
      autoinhibitory control of midbrain serotonergic neuronal firing. Here we examined
      the impact of serotonin(1A) receptor deletion on forebrain serotonin
      neurotransmission using in vivo microdialysis in the frontal cortex and ventral
      hippocampus of serotonin(1A) receptor mutant and wild-type mice. Baseline
      dialysate serotonin levels were significantly elevated in mutant animals as
      compared with wild-types both in frontal cortex (mutant = 0.44 +/- 0.05 n M; wild
      type = 0.28 +/- 0.03 n M) and hippocampus (mutant = 0.46 +/- 0.07 n M; wild-type
      = 0.27 +/- 0.04 n M). A stressor known to elicit enhanced anxiety-like behaviors
      in serotonin(1A) receptor mutants increased dialysate 5-HT levels in the frontal
      cortex of mutant mice by 144% while producing no alteration in cortical 5-HT in
      wild-type mice. There was no phenotypic difference in the effect of this stressor
      on serotonin levels in the hippocampus. Fluoxetine produced significantly greater
      increases in dialysate 5-HT content in serotonin(1A) receptor mutants as compared
      with wild-types, with two- and three-fold greater responses being observed in the
      hippocampus and frontal cortex, respectively. This phenotypic effect was mimicked
      in wild-types by pretreatment with the serotonin(1A) antagonist 4-iodo-N-[2-[4
      (methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (p-MPPI). These
      results indicate that deletion of central serotonin(1A) receptors results in a
      tonic disinhibition of central serotonin neurotransmission, with a greater
      dysregulation of serotonin release in the frontal cortex than ventral hippocampus
      under conditions of stress or increased interstitial serotonin levels.

PMID- 11299324
TI  - Involvement of calcium-calmodulin protein kinase but not mitogen-activated
      protein kinase in light-induced phase delays and Per gene expression in the
      suprachiasmatic nucleus of the hamster.
AB  - It is known that Ca(2+)-dependent phosphorylation of cAMP response element
      binding protein (CREB) and the rapid induction of mPer1 and mPer2, mouse period
      genes in the suprachiasmatic nucleus (SCN) are associated with light-induced
      phase shifting. The CREB/CRE transcriptional pathway has been shown to be
      activated by calcium/calmodulin dependent kinase II (CaMKII) and mitogen
      activated protein kinase (MAPK); however, there is a lack of evidence concerning
      whether the activation of CaMKII and/or MAPK elicited by photic stimuli are
      associated with the change in Per gene expression and behavioral phase shifting.
      In this experiment, we found there was an inhibitory effect by KN93, CaMKII
      inhibitor, on hamster Per1 and Per2 expression in the SCN and on phase delays in
      wheel running rhythm induced by light pulses. PD98059 and U0126, MAPK kinase
      inhibitors, however, affected neither light-induced Per1 and Per2 expression nor
      behavioral phase delays, even though PD98059 attenuated the light-induced
      phosphorylation of MAPK in the SCN. The present findings demonstrate that the
      light-induced activation of CaMKII plays an important role in the induction of
      Per1 and Per2 mRNA in the hamster SCN as well as phase shifting. These results
      suggest that gated induction of Per1 and/or Per2 genes through CaMKII-CREB/CRE
      accompanied with photic stimuli may be a critical step in phase shifting.

PMID- 11299325
TI  - Distinct properties of wild-type and the amyloidogenic human cystatin C variant
      of hereditary cerebral hemorrhage with amyloidosis, Icelandic type.
AB  - Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the
      cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy,
      leading to stroke. Wild-type and variant cystatin C are cysteine proteinase
      inhibitors which form concentration dependent inactive dimers; however, variant
      cystatin C dimerizes at lower concentrations and has an increased susceptibility
      to a serine protease. We studied the effect of the L68Q amino acid substitution
      on cystatin C properties, utilizing full length cystatin C purified in mild
      conditions from media of cells stably transfected with either the wild-type or
      variant cystatin C genes. The variant cystatin C forms fibrils in vitro
      detectable by electron microscopy in conditions in which the wild-type protein
      forms amorphous aggregates. We also show by circular dichroism, steady-state
      fluorescence and Fourier-transformed infrared spectroscopy that the amino acid
      substitution modifies cystatin C structure by destabilizing alpha-helical
      structures and exposing the tryptophan residue to a more polar environment,
      yielding a more unfolded molecule. These spectral changes demonstrate that
      variant cystatin C has a three-dimensional structure different from that of the
      wild-type protein. The structural differences between variant and wild-type
      cystatin C account for the susceptibility of the variant protein to unfolding,
      proteolysis and fibrillogenesis.

PMID- 11299326
TI  - Compensatory mechanisms enhance hippocampal acetylcholine release in transgenic
      mice expressing human acetylcholinesterase.
AB  - Central cholinergic neurotransmission was studied in learning-impaired transgenic
      mice expressing human acetylcholinesterase (hAChE-Tg). Total catalytic activity
      of AChE was approximately twofold higher in synaptosomes from hippocampus,
      striatum and cortex of hAChE-Tg mice as compared with controls (FVB/N mice).
      Extracellular acetylcholine (ACh) levels in the hippocampus, monitored by
      microdialysis in the absence or presence of 10(-8)-10(-3) M neostigmine in the
      perfusion fluid, were indistinguishable in freely moving control and hAChE-Tg
      mice. Muscarinic receptor functions were unchanged as indicated by similar
      effects of scopolamine on ACh release and of carbachol on inositol phosphate
      formation. However, when the mice were anaesthetized with halothane (0.8 vol. %),
      hippocampal ACh reached significantly lower levels in AChE-Tg mice as compared
      with controls. Also, the high-affinity choline uptake (HACU) in hippocampal
      synaptosomes from awake hAChE-Tg mice was accelerated but was reduced by
      halothane anaesthesia. Moreover, hAChE-Tg mice displayed increased motor activity
      in novel but not in familiar environment and presented reduced anxiety in the
      elevated plus-maze test. Systemic application of a low dose of physostigmine (100
      microgram/kg i.p.) normalized all of the enhanced parameters in hAChE-Tg mice:
      spontaneous motor activity, hippocampal ACh efflux and hippocampal HACU,
      attributing these parameters to the hypocholinergic state due to excessive AChE
      activity. We conclude that, in hAChE-Tg mice, hippocampal ACh release is up
      regulated in response to external stimuli thereby facilitating cholinergic
      neurotransmission. Such compensatory phenomena most likely play important roles
      in counteracting functional deficits in mammals with central cholinergic
      dysfunctions.

PMID- 11299328
TI  - Walker-256 tumor growth causes oxidative stress in rat brain.
AB  - The elevated rate of oxygen consumption and high amount of polyunsaturated fatty
      acids make the central nervous system vulnerable to oxidative stress. The effect
      of Walker-256 tumor growth on oxi-reduction indexes in the hypothalamus (HT),
      cortex (CT), hippocampus (HC) and cerebellum (CB) of male Wistar rats was
      investigated. The presence of the tumor caused an increase in thiobarbituric acid
      reactant substances (TBARs) in the HT, CB and HC. Due to tumor growth, the
      activity of glucose-6-phosphate dehydrogenase increased in the HT and CB, whereas
      citrate synthase activity was reduced in the HT, CT and CB. Therefore, the
      potential for generation of reducing power is increased in the cytosol and
      decreased in the mitochondria of various brain regions of Walker-256 tumor
      bearing rats. These changes occurred concomitantly with an unbalance in the brain
      enzymatic antioxidant system. The tumor decreased the activities of catalase in
      the HT and CB and of glutathione peroxidase in the HT, CB and HC, and raised the
      CuZn-superoxide dismutase activity in the HT, CB and HC. These combined findings
      indicate that Walker-256 tumor growth causes oxidative stress in the brain.

PMID- 11299327
TI  - Enhancement of 3,4-methylenedioxymethamphetamine neurotoxicity by the energy
      inhibitor malonate.
AB  - The acute and long-term effects of the local perfusion of 3,4
      methylenedioxymethamphetamine (MDMA) and the interaction with the mitochondrial
      inhibitor malonate (MAL) were examined in the rat striatum. MDMA, MAL or the
      combination of MAL with MDMA was reverse dialyzed into the striatum for 8 h via a
      microdialysis probe while extracellular dopamine (DA) and serotonin (5-HT) were
      measured. One week later, tissue immediately surrounding the probe was assayed
      for DA and 5-HT tissue content. Local perfusion of MDMA increased DA and 5-HT
      release but did not produce long-term depletion of DA or 5-HT in tissue. Malonate
      also increased both DA and 5-HT release but, in contrast to MDMA, produced only
      long-term depletion of DA. The combined perfusion of MDMA/MAL synergistically
      increased the release of DA and 5-HT and produced long-term depletion of both DA
      and 5-HT in tissue. These results support the conclusion that DA, compared with 5
      HT, neurons are more susceptible to mitochondrial inhibition. Moreover, MDMA,
      which does not normally produce DA depletion in the rat, exacerbated MAL-induced
      DA depletions. The effect of MDMA in combination with MAL to produce 5-HT
      depletion suggests a role for bio-energetic stress in MDMA-induced toxicity to 5
      HT neurons. Overall, these results highlight the importance of energy balance to
      the function of DA and 5-HT neurons and to the toxic effects of MDMA.

PMID- 11299329
TI  - ATP stimulates calcium-dependent glutamate release from cultured astrocytes.
AB  - ATP caused a dose-dependent, receptor-mediated increase in the release of
      glutamate and aspartate from cultured astrocytes. Using calcium imaging in
      combination HPLC we found that the increase in intracellular calcium coincided
      with an increase in glutamate and aspartate release. Competitive antagonists of
      P(2) receptors blocked the response to ATP. The increase in intracellular calcium
      and release of glutamate evoked by ATP were not abolished in low Ca(2+)-EGTA
      saline, suggesting the involvement of intracellular calcium stores. Pre-treatment
      of glial cultures with an intracellular Ca(2+) chelator abolished the stimulatory
      effects of ATP. Thapsigargin (1 microM), an inhibitor of Ca(2+)-ATPase from the
      Ca(2+) pump of internal stores, significantly reduced the calcium transients and
      the release of aspartate and glutamate evoked by ATP. U73122 (10 microM, a
      phospholipase C inhibitor, attenuated the ATP-stimulatory effect on calcium
      transients and blocked ATP-evoked glutamate release in astrocytes. Replacement of
      extracellular sodium with choline failed to influence ATP-induced glutamate
      release. Furthermore, inhibition of the glutamate transporters p-chloromercuri
      phenylsulfonic acid and Ltrans-pyrolidine-2,4-dicarboxylate failed to impair the
      ability of ATP to stimulate glutamate release from astrocytes. However, an anion
      transport inhibitor, furosemide, and a potent Cl(-) channel blocker, 5-nitro-2(3
      phenylpropylamino)-benzoate, reduced ATP-induced glutamate release. These results
      suggest that ATP stimulates excitatory amino acid release from astrocytes via a
      calcium-dependent anion-transport sensitive mechanism.

PMID- 11299330
TI  - A transient inhibition of mitochondrial ATP synthesis by nitric oxide synthase
      activation triggered apoptosis in primary cortical neurons.
AB  - In order to investigate the relationship between nitric oxide-mediated regulation
      of mitochondrial function and excitotoxicity, the role of mitochondrial ATP
      synthesis and intracellular redox status on the mode of neuronal cell death was
      studied. Brief (5 min) glutamate (100 microM) receptor stimulation in primary
      cortical neurons collapsed the mitochondrial membrane potential (psi(m)) and
      transiently (30 min) inhibited mitochondrial ATP synthesis, causing early (1 h)
      necrosis or delayed (24 h) apoptosis. The transient inhibition of ATP synthesis
      was paralleled to a loss of NADH, which was fully recovered shortly after the
      insult. In contrast, NADPH and the GSH/GSSG ratio were maintained, but
      progressively decreased thereafter. Twenty-four hours after glutamate treatment,
      ATP was depleted, a phenomenon associated with a persistent inhibition of
      mitochondrial succinate-cytochrome c reductase activity and delayed necrosis.
      Blockade of either nitric oxide synthase (NOS) activity or the mitochondrial
      permeability transition (MPT) pore prevented psi(m) collapse, the transient
      inhibition of mitochondrial ATP synthesis, early necrosis and delayed apoptosis.
      However, blockade of NOS activity, but not the MPT pore, prevented the inhibition
      of succinate-cytochrome c reductase activity and delayed ATP depletion and
      necrosis. From these results, we suggest that glutamate receptor-mediated NOS
      activation would trigger MPT pore opening and transient inhibition of ATP
      synthesis leading to apoptosis in a neuronal subpopulation, whereas other groups
      of neurons would undergo oxidative stress and persistent inhibition of ATP
      synthesis leading to necrosis.

PMID- 11299331
TI  - Bone morphogenetic proteins (BMP6 and BMP7) enhance the protective effect of
      neurotrophins on cultured septal cholinergic neurons during hypoglycemia.
AB  - The effects of two bone morphogenetic proteins (BMP6, BMP7), alone and in
      combination with neurotrophins, were tested on cultures of embryonic day 15 rat
      septum. A week-long exposure to BMP6 or BMP7 in the optimal concentration range
      of 2-5 n M increased the activity of choline acetyltransferase (ChAT) by 1.6-2
      fold, in both septal and combined septal-hippocampal cultures. The increase in
      ChAT activity reached significance after 4 days and continued to increase over an
      11-day exposure. Under control culture conditions neither BMP significantly
      altered the number of cholinergic neurons, and BMP effects on ChAT activity were
      less than linearly additive with those of nerve growth factor. The effects of
      BMPs and BMP + neurotrophin combinations were also assayed under two stress
      conditions: low-density culture and hypoglycemia. In low-density cultures BMPs
      and BMP + neurotrophin combinations preserved ChAT activity more effectively than
      neurotrophins alone. During 24 h hypoglycemic stress, BMPs alone did not preserve
      ChAT activity, but BMP + neurotrophin combinations preserved ChAT activity much
      more effectively than neurotrophins alone. These results demonstrate that BMP6
      and BMP7 enhance ChAT activity under control and low-density stress conditions,
      and that during a hypoglycemic stress their trophic effect requires and
      complements that exerted by neurotrophins.

PMID- 11299332
TI  - Inhibition of Ras extracellular-signal-regulated kinase (ERK) mediated signaling
      promotes ciliary neurotrophic factor (CNTF) expression in Schwann cells.
AB  - Ciliary neurotrophic factor (CNTF) can prevent injury-induced motor neuron death.
      However, it is also evident that expression of CNTF in Schwann cells is
      suppressed during nerve regeneration. In this report, we have addressed the
      mechanism underlying the down-regulation of CNTF expression in injured nerves
      using a mouse Schwann cell line IMS32 and mouse sciatic nerve. In IMS32 cells,
      activation of the Ras extracellular-signal-regulated kinase (ERK) pathway by
      adenoviral vector-mediated expression of dominant active MEK1 did not alter a
      basal level of CNTF expression, whereas inhibition of the Ras-ERK pathway by
      using adenoviral vectors resulted in a marked increase in CNTF expression. This
      inverse relation between before and after axotomy was also observed in mouse
      sciatic nerve. In the axotomized sciatic nerve, the phosphorylated ERK was
      markedly increased; in contrast, the expression of CNTF was markedly decreased.
      These findings suggest that an inactive state of ERK is crucial for the CNTF
      expression in Schwann cells, and that activation of ERK following nerve injury
      critically influences the expression of CNTF. This might well explain why CNTF is
      highly expressed in quiescent Schwann cells in the peripheral nervous system, and
      also why CNTF is not abundant in axotomized nerves or cultured Schwann cells in
      which the proliferation signal is obviously active.

PMID- 11299333
TI  - When transgenes wander, should we worry?

PMID- 11299334
TI  - Tribute to Folke Skoog.

PMID- 11299335
TI  - Characterization of a tobacco Bright Yellow 2 cell line expressing the
      tetracycline repressor at a high level for strict regulation of transgene
      expression.
AB  - Manipulating the expression of a transgene in transient and stable transformed
      cells is a requirement for many functional analyses. We have investigated the use
      of the tetracycline-dependent gene expression system developed by Gatz et al.
      (1992) in tobacco (Nicotiana tabacum L. cv Bright Yellow 2 [BY2]) cells, the most
      widely used plant cell culture. We have selected a BY2 cell line, named BY2
      tetracycline repressor (tetR) 17, which expresses the tetR at a high level, and
      have evaluated the capacity of this cell line to suppress the expression of a
      green fluorescent protein reporter gene under the control of the "Triple-Op"
      promoter in the absence of tetracycline in a large number of independent
      transformants. The ability to induce the expression of green fluorescent protein
      after treatment by anhydrotetracycline in the same transformants was also
      analyzed. BY2-tetR17 cells were demonstrated to be excellent recipient cells for
      recovery of clonal cell lines with a highly controlled regulation of the
      introduced transgene.

PMID- 11299336
TI  - The nitrate reductase circadian system. The central clock dogma contra multiple
      oscillatory feedback loops.

PMID- 11299337
TI  - Non-photochemical quenching. A response to excess light energy.

PMID- 11299339
TI  - Guard cell volume and pressure measured concurrently by confocal microscopy and
      the cell pressure probe.
AB  - Guard cell turgor pressures in epidermal peels of broad bean (Vicia faba) were
      measured and controlled with a pressure probe. At the same time, images of the
      guard cell were acquired using confocal microscopy. To obtain a clear image of
      guard cell volume, a fluorescent dye that labels the plasma membrane was added to
      the solution bathing the epidermal peel. At each pressure, 17 to 20 optical
      sections (each 2 microm thick) were acquired. Out-of-focus light in these images
      was removed using blind deconvolution, and volume was estimated using direct
      linear integration. As pressure was increased from as low as 0.3 MPa to as high
      as 5.0 MPa, guard cell volume increased in a saturating fashion. The elastic
      modulus was calculated from these data and was found to range from approximately
      2 to 40 MPa. The data allow inference of guard cell osmotic content from stomatal
      aperture and facilitate accurate mechanistic modeling of epidermal water
      relations and stomatal functioning.

PMID- 11299338
TI  - Arabidopsis genes encoding components of the chloroplastic protein import
      apparatus.
AB  - The process of protein import into plastids has been studied extensively using
      isolated pea (Pisum sativum) chloroplasts. As a consequence, virtually all of the
      known components of the proteinaceous apparatus that mediates import were
      originally cloned from pea. With the recent completion of the Arabidopsis genome
      sequencing project, it is now possible to identify putative homologs of the
      import components in this species. Our analysis has revealed that Arabidopsis
      homologs with high sequence similarity exist for all of the pea import complex
      subunits, making Arabidopsis a valid model for further study of this system.
      Multiple homologs can be identified for over one-half of the components. In all
      but one case it is known that more than one of the putative isoforms for a
      particular subunit are expressed. Thus, it is possible that multiple types of
      import complexes are present within the same cell, each having a unique affinity
      for different chloroplastic precursor proteins, depending upon the exact mix of
      isoforms it contains. Sequence analysis of the putative Arabidopsis homologs for
      the chloroplast protein import apparatus has revealed many questions concerning
      subunit function and evolution. It should now be possible to use the genetic
      tools available in Arabidopsis, including the generation of knockout mutants and
      antisense technology, to address these questions and learn more about the
      molecular functions of each of the components during the import process.

PMID- 11299340
TI  - Expression of bar in the plastid genome confers herbicide resistance.
AB  - Phosphinothricin (PPT) is the active component of a family of environmentally
      safe, nonselective herbicides. Resistance to PPT in transgenic crops has been
      reported by nuclear expression of a bar transgene encoding phosphinothricin
      acetyltransferase, a detoxifying enzyme. We report here expression of a bacterial
      bar gene (b-bar1) in tobacco (Nicotiana tabacum cv Petit Havana) plastids that
      confers field-level tolerance to Liberty, an herbicide containing PPT. We also
      describe a second bacterial bar gene (b-bar2) and a codon-optimized synthetic bar
      (s-bar) gene with significantly elevated levels of expression in plastids (>7% of
      total soluble cellular protein). Although these genes are expressed at a high
      level, direct selection thus far did not yield transplastomic clones, indicating
      that subcellular localization rather than the absolute amount of the enzyme is
      critical for direct selection of transgenic clones. The codon-modified s-bar gene
      is poorly expressed in Escherichia coli, a common enteric bacterium, due to
      differences in codon use. We propose to use codon usage differences as a
      precautionary measure to prevent expression of marker genes in the unlikely event
      of horizontal gene transfer from plastids to bacteria. Localization of the bar
      gene in the plastid genome is an attractive alternative to incorporation in the
      nuclear genome since there is no transmission of plastid-encoded genes via
      pollen.

PMID- 11299341
TI  - Release of reactive oxygen intermediates (superoxide radicals, hydrogen peroxide,
      and hydroxyl radicals) and peroxidase in germinating radish seeds controlled by
      light, gibberellin, and abscisic acid.
AB  - Germination of radish (Raphanus sativus cv Eterna) seeds can be inhibited by far
      red light (high-irradiance reaction of phytochrome) or abscisic acid (ABA).
      Gibberellic acid (GA3) restores full germination under far-red light. This
      experimental system was used to investigate the release of reactive oxygen
      intermediates (ROI) by seed coats and embryos during germination, utilizing the
      apoplastic oxidation of 2',7'-dichlorofluorescin to fluorescent 2',7'
      dichlorofluorescein as an in vivo assay. Germination in darkness is accompanied
      by a steep rise in ROI release originating from the seed coat (living aleurone
      layer) as well as the embryo. At the same time as the inhibition of germination,
      far-red light and ABA inhibit ROI release in both seed parts and GA3 reverses
      this inhibition when initiating germination under far-red light. During the later
      stage of germination the seed coat also releases peroxidase with a time course
      affected by far-red light, ABA, and GA3. The participation of superoxide
      radicals, hydrogen peroxide, and hydroxyl radicals in ROI metabolism was
      demonstrated with specific in vivo assays. ROI production by germinating seeds
      represents an active, developmentally controlled physiological function,
      presumably for protecting the emerging seedling against attack by pathogens.

PMID- 11299342
TI  - Cell-type-specific expression of plant cytochrome c mRNA in developing flowers
      and roots.
AB  - We have used RNA in situ hybridization to analyze the expression of transcripts
      encoding cytochrome c in different tissues and organs of sunflower (Helianthus
      annuus). Although northern-blot hybridization experiments indicate that the
      relative abundance of transcripts does not vary greatly, we have detected
      important changes in localization during flower development. Enhanced expression
      is observed in floral meristems as soon as they are discernible from the central
      portion of the capitulum containing the inflorescence meristem. As flowers
      develop, labeling is observed in all developing floral organ primordia. Later in
      development, expression in petals is reduced, and only the central portion of the
      flower becomes labeled. During the process of stamen formation, hybridization
      signals were obtained mainly in anthers. Less developed flowers at this stage
      showed expression through the archesporial tissue. During meiosis, the label was
      observed mainly in tapetal cells. Specific expression patterns, similar to those
      obtained for sunflower, were observed when Arabidopsis flowers were analyzed with
      a homologous cytochrome c probe. Specific patterns of expression were also
      observed in young sunflower roots. In this case, enhanced expression was detected
      in developing endodermis and pericycle and in protoxylem initials. We conclude
      that cell-specific mechanisms operate to regulate the abundance of cytochrome c
      encoding transcripts in different plant tissues. The overlap between the
      expression patterns of the nuclear encoded cytochrome c gene and some
      mitochondrial genes suggests the existence of coordinated mechanisms of
      expression.

PMID- 11299343
TI  - Association of spectrin-like proteins with the actin-organized aggregate of
      endoplasmic reticulum in the Spitzenkorper of gravitropically tip-growing plant
      cells.
AB  - Spectrin-like epitopes were immunochemically detected and immunofluorescently
      localized in gravitropically tip-growing rhizoids and protonemata of characean
      algae. Antiserum against spectrin from chicken erythrocytes showed cross
      reactivity with rhizoid proteins at molecular masses of about 170 and 195 kD.
      Confocal microscopy revealed a distinct spherical labeling of spectrin-like
      proteins in the apices of both cell types tightly associated with an apical actin
      array and a specific subdomain of endoplasmic reticulum (ER), the ER aggregate.
      The presence of spectrin-like epitopes, the ER aggregate, and the actin
      cytoskeleton are strictly correlated with active tip growth. Application of
      cytochalasin D and A23187 has shown that interfering with actin or with the
      calcium gradient, which cause the disintegration of the ER aggregate and abolish
      tip growth, inhibits labeling of spectrin-like proteins. At the beginning of the
      graviresponse in rhizoids the labeling of spectrin-like proteins remained in its
      symmetrical position at the cell tip, but was clearly displaced to the upper
      flank in gravistimulated protonemata. These findings support the hypothesis that
      a displacement of the Spitzenkorper is required for the negative gravitropic
      response in protonemata, but not for the positive gravitropic response in
      rhizoids. It is evident that the actin/spectrin system plays a role in
      maintaining the organization of the ER aggregate and represents an essential part
      in the mechanism of gravitropic tip growth.

PMID- 11299344
TI  - Carrier-mediated uptake and phloem systemy of a 350-Dalton chlorinated xenobiotic
      with an alpha-amino acid function.
AB  - In a previous paper we have shown that epsilon-(phenoxyalkanecarboxylyl)-L-Lys
      conjugates are potent inhibitors of amino acid transport systems and that it is
      possible to modulate the uptake inhibition by hydrophobic or hydrophilic
      additions in the 4-position of the aromatic ring (J.F. Chollet, C. Deletage, M.
      Faucher, L. Miginiac, J.L. Bonnemain [1997] Biochem Biophys Acta 1336: 331-341).
      In this report we demonstrate that epsilon-(2,4-dichlorophenoxyacetyl)-L-Lys
      (2,4D-Lys), one of the largest molecules of the series and one of the most potent
      inhibitors, is a highly permeant conjugate. Uptake of 2,4D-Lys by broad bean
      (Vicia faba) leaf discs is mediated by an active carrier system (Km1 = 0.2 mM;
      Vmax1 = 2.4 nmol x cm(-2) x h(-1) at pH 5.0) complemented by an important
      diffusive component. Among the compounds tested (neutral, basic, and acidic amino
      acids, auxin, glutathione, and sugars), only the aromatic amino acids clearly
      compete with 2,4D-Lys. The conjugate accumulates in the vein network, is exported
      toward the growing organs, and exhibits a distribution pattern different from
      that of the herbicide moiety. However, over time 2,4D-Lys progressively splits
      into 2,4D and lysine. Analyses by high-performance liquid chromatography and
      liquid scintillation spectrometry of the phloem sap collected from the castor
      bean system, used as a systemy test, indicate decreasing capacities of 2,4D, 2,4D
      Lys, and glyphosate, respectively, to move from the epidermis cell wall to the
      sieve element. Our results show that it is possible to design synthesis of large
      size xenobiotics (approximately 350 D) with a lipophilic pole, exhibiting high
      mobility within the vascular system.

PMID- 11299345
TI  - Evidence for non-circadian light/dark-regulated expression of Hsp70s in spinach
      leaves.
AB  - Expression of six Hsp70s in spinach (Spinacia oleracea cv Longstanding
      Bloomsdale) leaves grown under isothermal conditions is regulated by a light/dark
      (L/D) mechanism distinctly different from the light-regulated mechanism for the
      chlorophyll a/b-binding protein (cab) or small subunit of ribulose-1,5
      bisphosphate carboxylase oxygenase (rbcS). Subjecting entrained plants to two or
      three L/D cycles within a 24-h period resulted in an equal number of oscillations
      in expression for five out of six 70-kD heat shock proteins (Hsp70s). Three
      cycles appear to be the maximum, as shorter L/D treatments do not consistently
      increase the number of cycles in a 24-h period. The expression response of Hsp70s
      to L/D is overridden by heat shock. Protein disulfide isomerase, a second
      molecular chaperone of the endoplasmic reticulum, has an expression pattern in
      entrained plants that is similar to hsc70-2, the endoplasmic reticulum luminal
      Hsp70 binding protein. The parallel expression patterns for the various Hsp70s
      and protein disulfide isomerase indicate a likely general coordinate L/D
      regulation for molecular chaperones in plants. Multiple inductions in response to
      successive L/D treatments within a 24-h period in entrained plants for five of
      six Hsp70s support the conclusion that expression is not a consequence of
      circadian control, but instead is independently cued by non-circadian-mediated
      L/D signals where peak Hsp70 expression precedes the daily thermoperiod maximum.

PMID- 11299346
TI  - Salt-induced expression of the vacuolar H+-ATPase in the common ice plant is
      developmentally controlled and tissue specific.
AB  - For salinity stress tolerance in plants, the vacuolar type H+-ATPase (V-ATPase)
      is of prime importance in energizing sodium sequestration into the central
      vacuole and it is known to respond to salt stress with increased expression and
      enzyme activity. In this work we provide information that the expressional
      response to salinity of the V-ATPase is regulated tissue and cell specifically
      under developmental control in the facultative halophyte common ice plant
      (Mesembryanthemum crystallinum). By transcript analysis of subunit E of the V
      ATPase, amounts did not change in response to salinity stress in juvenile plants
      that are not salt-tolerant. In a converse manner, in halotolerant mature plants
      the transcript levels increased in leaves, but not in roots when salt stressed
      for 72 h. By in situ hybridizations and immunocytological protein analysis,
      subunit E was shown to be synthesized in all cell types. During salt stress,
      signal intensity declined in root cortex cells and in the cells of the root
      vascular cylinder. In salt-stressed leaves of mature plants, the strongest
      signals were localized surrounding the vasculature. Within control cells and with
      highest abundance in mesophyll cells of salt-treated leaves, accumulation of
      subunit E protein was observed in the cytoplasm, indicating its presence not only
      in the tonoplast, but also in other endoplasmic compartments.

PMID- 11299347
TI  - Developmental and stress regulation of RCI2A and RCI2B, two cold-inducible genes
      of arabidopsis encoding highly conserved hydrophobic proteins.
AB  - The capability of most higher plants to tolerate environmental conditions
      strongly depends on their developmental stage. In addition, environmental factors
      have pleiotropic effects on many developmental processes. The interaction between
      plant development and environmental conditions implies that some genes must be
      regulated by both environmental factors and developmental cues. To understand
      their developmental regulation and obtain possible clues on their functions, we
      have isolated genomic clones for RCI2A and RCI2B, two genes from Arabidopsis
      ecotype Columbia (Col), whose expression is induced in response to low
      temperature, dehydration, salt stress, and abscisic acid. The promoters of RCI2A
      and RCI2B were fused to the uidA (GUS)-coding sequence and the resulting
      constructs used to transform Arabidopsis. GUS activity was analyzed in transgenic
      plants during development under both stressed and unstressed conditions.
      Transgenic plants with either the RCI2A or RCI2B promoter showed strong GUS
      expression during the first stages of seed development and germination, in
      vascular bundles, pollen, and most interestingly in guard cells. When transgenic
      plants were exposed to low temperature, dehydration, salt stress, or abscisic
      acid, reporter gene expression was induced in most tissues. These results
      indicate that RCI2A and RCI2B are regulated at transcriptional level during plant
      development and in response to different environmental stimuli and treatments.
      The potential role of RCI2A and RCI2B in plant development and stress response is
      discussed.

PMID- 11299348
TI  - Tuber physiology and properties of starch from tubers of transgenic potato plants
      with altered plastidic adenylate transporter activity.
AB  - We showed recently that antisense plants with decreased activity of the plastidic
      ATP/ADP-transporter protein exhibit drastically reduced levels of starch and a
      decreased amylose/amylopectin ratio, whereas sense plants with increased activity
      of the transporter possessed more starch than wild-type plants and an increased
      amylose/amylopectin ratio. In this paper we investigate the effect of altered
      plastidic ATP/ADP-transporter protein expression on primary metabolism and
      granule morphology in more detail. Tuber tissues from antisense and sense plants
      exhibited substantially increased respiratory activity compared with the wild
      type. Tubers from antisense plants contained markedly increased levels of free
      sugars, UDP-Glc, and hexose phosphates, whereas phosphoenolpyruvate, isocitrate,
      ATP, ADP, AMP, UTP, UDP, and inorganic pyrophosphate levels were slightly
      decreased. In contrast, tubers from sense plants revealed a slight increase in
      adenine and uridine nucleotides and in the levels of inorganic pyrophosphate,
      whereas no significant changes in the levels of soluble sugars and metabolites
      were observed. Antisense tubers contained 50% reduced levels of ADP-Glc, whereas
      sense tubers contained up to 2-fold increased levels of this sole precursor for
      starch biosynthesis. Microscopic examination of starch grain morphology revealed
      that the size of starch grains from antisense tubers was substantially smaller
      (50%) compared with the wild type. The large starch grains from sense tubers
      appeared of a more angular morphology, which differed to the more ellipsoid shape
      of wild type grains. The results suggest a close interaction between plastidial
      adenylate transport and starch biosynthesis, indicating that ADP-Glc
      pyrophosphorylase is ATP-limited in vivo and that changes in ADP-Glc
      concentration determine starch yield, as well as granule morphology. Possible
      factors linking starch synthesis and respiration are discussed.

PMID- 11299349
TI  - Iron stress-induced changes in root epidermal cell fate are regulated
      independently from physiological responses to low iron availability.
AB  - Iron-overaccumulating mutants were investigated with respect to changes in
      epidermal cell patterning and root reductase activity in response to iron
      starvation. In all mutants under investigation, ferric chelate reductase activity
      was up-regulated both in the presence and absence of iron in the growth medium.
      The induction of transfer cells in the rhizodermis appeared to be iron regulated
      in the pea (Pisum sativum L. cv Dippes Gelbe Viktoria and cv Sparkle) mutants
      bronze and degenerated leaflets, but not in roots of the tomato (Lycopersicon
      esculentum Mill. cv Bonner Beste) mutant chloronerva, suggesting that in
      chloronerva iron cannot be recognized by putative sensor proteins. Experiments
      with split-root plants supports the hypothesis that Fe(III) chelate reductase is
      regulated by a shoot-borne signal molecule, communicating the iron status of the
      shoot to the roots. In contrast, the formation of transfer cells was dependent on
      the local concentration of iron, implying that this shoot signal does not affect
      their formation. Different repression curves of the two responses imply that the
      induction of transfer cells occurs after the enhancement of electron transfer
      across the plasma membrane rather than being causally linked. Similar to transfer
      cells, the formation of extra root hairs in the Arabidopsis mutant man1 was
      regulated by the iron concentration of the growth medium and was unaffected by
      interorgan signaling.

PMID- 11299351
TI  - Xylem cavitation in the leaf of Prunus laurocerasus and its impact on leaf
      hydraulics.
AB  - This paper reports how water stress correlates with changes in hydraulic
      conductivity of stems, leaf midrib, and whole leaves of Prunus laurocerasus.
      Water stress caused cavitation-induced dysfunction in vessels of P. laurocerasus.
      Cavitation was detected acoustically by counts of ultrasonic acoustic emissions
      and by the loss of hydraulic conductivity measured by a vacuum chamber method.
      Stems and midribs were approximately equally vulnerable to cavitations. Although
      midribs suffered a 70% loss of hydraulic conductance at leaf water potentials of 
      1.5 MPa, there was less than a 10% loss of hydraulic conductance in whole leaves.
      Cutting and sealing the midrib 20 mm from the leaf base caused only a 30% loss of
      conduction of the whole leaf. A high-pressure flow meter was used to measure
      conductance of whole leaves and as the leaf was progressively cut back from tip
      to base. These data were fitted to a model of hydraulic conductance of leaves
      that explained the above results, i.e. redundancy in hydraulic pathways whereby
      water can flow around embolized regions in the leaf, makes whole leaves
      relatively insensitive to significant changes in conductance of the midrib. The
      onset of cavitation events in P. laurocerasus leaves correlated with the onset of
      stomatal closure as found recently in studies of other species in our laboratory.

PMID- 11299350
TI  - Study of the role of antimicrobial glucosinolate-derived isothiocyanates in
      resistance of Arabidopsis to microbial pathogens.
AB  - Crude aqueous extracts from Arabidopsis leaves were subjected to chromatographic
      separations, after which the different fractions were monitored for antimicrobial
      activity using the fungus Neurospora crassa as a test organism. Two major
      fractions were obtained that appeared to have the same abundance in leaves from
      untreated plants versus leaves from plants challenge inoculated with the fungus
      Alternaria brassicicola. One of both major antimicrobial fractions was purified
      to homogeneity and identified by 1H nuclear magnetic resonance, gas
      chromatography/electron impact mass spectrometry, and gas chromatography/chemical
      ionization mass spectrometry as 4-methylsulphinylbutyl isothiocyanate (ITC). This
      compound has previously been described as a product of myrosinase-mediated
      breakdown of glucoraphanin, the predominant glucosinolate in Arabidopsis leaves.
      4-Methylsulphinylbutyl ITC was found to be inhibitory to a wide range of fungi
      and bacteria, producing 50% growth inhibition in vitro at concentrations of 28
      microM for the most sensitive organism tested (Pseudomonas syringae). A
      previously identified glucosinolate biosynthesis mutant, gsm1-1, was found to be
      largely deficient in either of the two major antimicrobial compounds, including 4
      methylsulphinylbutyl ITC. The resistance of gsm1-1 was compared with that of wild
      type plants after challenge with the fungi A. brassicicola, Plectosphaerella
      cucumerina, Botrytis cinerea, Fusarium oxysporum, or Peronospora parasitica, or
      the bacteria Erwinia carotovora or P. syringae. Of the tested pathogens, only F.
      oxysporum was found to be significantly more aggressive on gsm1-1 than on wild
      type plants. Taken together, our data suggest that glucosinolate-derived
      antimicrobial ITCs can play a role in the protection of Arabidopsis against
      particular pathogens.

PMID- 11299352
TI  - Two loci control phytoglycogen production in the monocellular green alga
      Chlamydomonas reinhardtii.
AB  - The STA8 locus of Chlamydomonas reinhardtii was identified in a genetic screen as
      a factor that controls starch biosynthesis. Mutations of STA8 cause a significant
      reduction in the amount of granular starch produced during nutrient limitation
      and accumulate phytoglycogen. The granules remaining in sta8 mutants are
      misshapen, and the abundance of amylose and long chains in amylopectin is
      altered. Mutations of the STA7 locus, which completely lack isoamylase activity,
      also cause accumulation of phytoglycogen, although sta8 and sta7 mutants differ
      in that there is a complete loss of granular starch in the latter. This is the
      first instance in which mutations of two different genetic elements in one plant
      species have been shown to cause phytoglycogen accumulation. An analytical
      procedure that allows assay of isoamylase in total extracts was developed and
      used to show that sta8 mutations cause a 65% reduction in the level of this
      activity. All other enzymes known to be involved in starch biosynthesis were
      shown to be unaffected in sta8 mutants. The same amount of total isoamylase
      activity (approximately) as that present in sta8 mutants was observed in
      heterozygous triploids containing two sta7 mutant alleles and one wild-type
      allele. This strain, however, accumulates normal levels of starch granules and
      lacks phytoglycogen. The total level of isoamylase activity, therefore, is not
      the major determinant of whether granule production is reduced and phytoglycogen
      accumulates. Instead, a qualitative property of the isoamylase that is affected
      by the sta8 mutation is likely to be the critical factor in phytoglycogen
      production.

PMID- 11299353
TI  - Biochemical characterization of wild-type and mutant isoamylases of Chlamydomonas
      reinhardtii supports a function of the multimeric enzyme organization in
      amylopectin maturation.
AB  - Chlamydomonas reinhardtii mutants of the STA8 gene produce reduced amounts of
      high amylose starch and phytoglycogen. In contrast to the previously described
      phytoglycogen-producing mutants of C. reinhardtii that contain no residual
      isoamylase activity, the sta8 mutants still contained 35% of the normal amount of
      enzyme activity. We have purified this residual isoamylase and compared it with
      the wild-type C. reinhardtii enzyme. We have found that the high-mass multimeric
      enzyme has reduced its average mass at least by one-half. This coincides with the
      disappearance of two out of the three activity bands that can be seen on zymogram
      gels. Wild-type and mutant enzymes are shown to be located within the plastid. In
      addition, they both act by cleaving off the outer branches of polysaccharides
      with no consistent difference in enzyme specificity. Because the mutant enzyme
      was demonstrated to digest phytoglycogen to completion in vitro, we propose that
      its inability to do so in vivo supports a function of the enzyme complex
      architecture in the processing of pre-amylopectin chains.

PMID- 11299354
TI  - Pea legumin overexpressed in wheat endosperm assembles into an ordered
      paracrystalline matrix.
AB  - Legumin, a major component of pea seed storage vacuoles, is synthesized by a
      number of paralogous genes. The polypeptides are cleaved posttranslationally and
      can form mixed hexamers. This heterogeneity hampers structural studies, based on
      the production of hexamer crystals in vitro. To study a single type of homogenous
      legumin we produced pea legumin A in transgenic wheat (Triticum aestivum)
      endosperm where prolamins are predominant and only small amounts of globulins
      accumulate in separate inclusions. We demonstrated that the legumin precursor was
      cleaved posttranslationally and we confirmed assembly into 11S hexamers. Legumin
      was deposited within specific regions of the inclusion bodies. Angular legumin
      crystals extended from the inclusion bodies into the vacuole, correlating with
      the high legumin content. This suggests that the high-level production of a
      single type of legumin polypeptide resulted in the spontaneous formation of
      crystals in vivo. The use of a heterologous cereal system such as wheat endosperm
      to produce, isolate, and recrystallize homogenous 11S legume globulins offers
      exciting possibilities for structural analysis and characterization of these
      important seed storage proteins.

PMID- 11299355
TI  - Real time visualization of 13N-translocation in rice under different
      environmental conditions using positron emitting Ttacer imaging system.
AB  - The ammonium ion is an indispensable nitrogen source for crops, especially paddy
      rice (Oryza sativa L. cv Nipponbare). Until now, it has been impossible to
      measure ammonium uptake and nitrogen movement in plants in real time. Using the
      new technologies of PETIS (positron emitting tracer imaging system) and PMPS
      (positron multi-probe system), we were able to visualize the real time
      translocation of nitrogen and water in rice plants. We used positron-emitting 13N
      labeled ammonium (13NH4+) and 15O-water to monitor the movement. In plants
      cultured under normal conditions, 13NH4+ supplied to roots was taken up, and a
      13N signal was detected at the discrimination center, the basal part of the
      shoots, within 2 minutes. This rapid translocation of (13)N was almost completely
      inhibited by a glutamine synthetase inhibitor, methionine sulfoximine. In
      general, nitrogen deficiency enhanced 13N translocation to the discrimination
      center. In the dark, 13N translocation to the discrimination center was
      suppressed to 40% of control levels, whereas 15O-water flow from the root to the
      discrimination center stopped completely in the dark. In abscisic acid-treated
      rice, 13N translocation to the discrimination center was doubled, whereas
      translocation to leaves decreased to 40% of control levels. Pretreatment with NO3
      for 36 hours increased 13N translocation from the roots to the discrimination
      center to 5 times of control levels. These results suggest that ammonium
      assimilation (from the roots to the discrimination center) depends passively on
      water flow, but actively on NH4+-transporter(s) or glutamine synthetase(s).

PMID- 11299356
TI  - The cyclization of farnesyl diphosphate and nerolidyl diphosphate by a purified
      recombinant delta-cadinene synthase.
AB  - The first step in the conversion of the isoprenoid intermediate, farnesyl
      diphosphate (FDP), to sesquiterpene phytoalexins in cotton (Gossypium barbadense)
      plants is catalyzed by delta-cadinene (CDN) synthase. CDN is the precursor of
      desoxyhemigossypol and hemigossypol defense sesquiterpenes. In this paper we have
      studied the mechanism for the cyclization of FDP and the putative intermediate,
      nerolidyl diphosphate, to CDN. A purified recombinant CDN synthase (CDN1-C1)
      expressed in Escherichia coli from CDN1-C1 cDNA isolated from Gossypium arboreum
      cyclizes (1RS)-[1-2H](E, E)-FDP to >98% [5-2H]and [11-2H]CDN. Enzyme reaction
      mixtures cyclize (3RS)-[4,4,13,13,13-2H5]-nerolidyl diphosphate to 62.1%
      [8,8,15,15,15-2H5]-CDN, 15.8% [6,6,15,15,15-2H5]-alpha-bisabolol, 8.1%
      [6,6,15,15,15-2H5]-(beta)-bisabolene, 9.8% [4,4,13,13-2H4]-(E)-beta-farnesene,
      and 4.2% unknowns. Competitive studies show that (3R)-nerolidyl diphosphate is
      the active enantiomer of (3RS)-nerolidyl diphosphate that cyclized to CDN. The
      kcat/Km values demonstrate that the synthase uses (E,E)-FDP as effectively as
      (3R)-nerolidyl diphosphate in the formation of CDN. Cyclization studies with (3R)
      nerolidyl diphosphate show that the formation of CDN, (E)-beta-farnesene, and
      beta-bisabolene are enzyme dependent, but the formation of alpha-bisabolol in the
      reaction mixtures was a Mg2+-dependent solvolysis of nerolidyl diphosphate.
      Enzyme mechanisms are proposed for the formation of CDN from (E,E)-FDP and for
      the formation of CDN, (E)-beta-farnesene, and beta-bisabolene from (3RS)
      nerolidyl diphosphate. The primary structures of cotton CDN synthase and tobacco
      epi-aristolochene synthase show 48% identity, suggesting similar three
      dimensional structures. We used the SWISS-MODEL to test this. The two enzymes
      have the same overall structure consisting of two alpha-helical domains and epi
      aristolochene synthase is a good model for the structure of CDN synthase. Several
      amino acids in the primary structures of both synthases superimpose. The amino
      acids having catalytic roles in epi-aristochene synthase are substituted in the
      CDN synthase and may be related to differences in catalytic properties.

PMID- 11299357
TI  - Genetic analysis of amino acid accumulation in opaque-2 maize endosperm.
AB  - The opaque-2 mutation in maize (Zea mays) is associated with an increased level
      of free amino acids (FAA) in the mature endosperm. In particular, there is a high
      concentration of lysine, the most limiting essential amino acid. To investigate
      the basis for the high-FAA phenotype of opaque-2 maize, we characterized amino
      acid accumulation during endosperm development of several wild-type and opaque-2
      inbreds. Oh545o2 was found to have an exceptionally high level of FAA, in
      particular those derived from aspartate (Asp) and intermediates of glycolysis.
      The FAA content in Oh545o2 is 12 times greater than its wild-type counterpart,
      and three and 10 times greater than in Oh51Ao2 and W64Ao2, respectively. We
      crossed Oh545o2 to Oh51Ao2 and analyzed the F(2:3) progeny to identify genetic
      loci linked with the high FAA level in these mutants. Quantitative trait locus
      mapping identified four significant loci that account for about 46% of the
      phenotypic variance. One locus on the long arm of chromosome 2 is coincident with
      genes encoding a monofunctional Asp kinase 2 and a bifunctional Asp kinase-homo
      Ser dehydrogenase-2, whereas another locus on the short arm of chromosome 3 is
      linked with a cytosolic triose phosphate isomerase 4. The results suggest an
      alternation of amino acid and carbon metabolism leads to overproduction and
      accumulation of FAA in opaque-2 mutants.

PMID- 11299358
TI  - Aspartate kinase 2. A candidate gene of a quantitative trait locus influencing
      free amino acid content in maize endosperm.
AB  - The maize (Zea mays) Oh545o2 inbred accumulates an exceptionally high level of
      free amino acids, especially lysine (Lys), threonine (Thr), methionine, and iso
      leucine. In a cross between Oh545o2 and Oh51Ao2, we identified several
      quantitative trait loci linked with this phenotype. One of these is on the long
      arm of chromosome 2 and is linked with loci encoding aspartate (Asp) kinase 2 and
      Asp kinase (AK)-homoserine dehydrogenase (HSDH) 2. To investigate whether these
      enzymes can contribute to the high levels of Asp family amino acids, we measured
      their specific activity and feedback inhibition properties, as well as activities
      of several other key enzymes involved in Lys metabolism. We did not find a
      significant difference in total activity of dihydrodipicolinate synthase, HSDH,
      and Lys ketoglutarate reductase between these inbreds, and the feedback
      inhibition properties of HSDH and dihyrodipicolinate synthase by Lys and/or Thr
      were similar. The most significant difference we found between Oh545o2 and
      Oh51Ao2 is feedback inhibition of AK by Lys but not Thr. AK activity in Oh545o2
      is less sensitive to Lys inhibition than that in Oh51Ao2, with a Lys I50 twice
      that of Oh51Ao2. AK activity in Oh545o2 endosperm is also higher than in Oh51Ao2
      at 15 d after pollination, but not 20 d after pollination. The results indicate
      that the Lys-sensitive Asp kinase 2, rather than the Thr-sensitive AK-HSDH2, is
      the best candidate gene for the quantitative trait locus affecting free amino
      acid content in Oh545o2.

PMID- 11299359
TI  - Evolution of floral meristem identity genes. Analysis of Lolium temulentum genes
      related to APETALA1 and LEAFY of Arabidopsis.
AB  - Flowering (inflorescence formation) of the grass Lolium temulentum is strictly
      regulated, occurring rapidly on exposure to a single long day (LD). During floral
      induction, L. temulentum differs significantly from dicot species such as
      Arabidopsis in the expression, at the shoot apex, of two APETALA1 (AP1)-like
      genes, LtMADS1 and LtMADS2, and of L. temulentum LEAFY (LtLFY). As shown by in
      situ hybridization, LtMADS1 and LtMADS2 are expressed in the vegetative shoot
      apical meristem, but expression increases strongly within 30 h of LD floral
      induction. Later in floral development, LtMADS1 and LtMADS2 are expressed within
      spikelet and floret meristems and in the glume and lemma primordia. It is
      interesting that LtLFY is detected quite late (about 12 d after LD induction)
      within the spikelet meristems, glumes, and lemma primordia. These patterns
      contrast with Arabidopsis, where LFY and AP1 are consecutively activated early
      during flower formation. LtMADS2, when expressed in transgenic Arabidopsis plants
      under the control of the AP1 promoter, could partially complement the organ
      number defect of the severe ap1-15 mutant allele, confirming a close relationship
      between LtMADS2 and AP1.

PMID- 11299360
TI  - Non-targeted and targeted protein movement through plasmodesmata in leaves in
      different developmental and physiological states.
AB  - Plant cells rely on plasmodesmata for intercellular transport of small signaling
      molecules as well as larger informational macromolecules such as proteins. A
      green fluorescent protein (GFP) reporter and low-pressure microprojectile
      bombardment were used to quantify the degree of symplastic continuity between
      cells of the leaf at different developmental stages and under different growth
      conditions. Plasmodesmata were observed to be closed to the transport of GFP or
      dilated to allow the traffic of GFP. In sink leaves, between 34% and 67% of the
      cells transport GFP (27 kD), and between 30% and 46% of the cells transport
      double GFP (54 kD). In leaves in transition transport was reduced; between 21%
      and 46% and between 2% and 9% of cells transport single and double GFP,
      respectively. Thus, leaf age dramatically affects the ability of cells to
      exchange proteins nonselectively. Further, the number of cells allowing GFP or
      double GFP movement was sensitive to growth conditions because greenhouse-grown
      plants exhibited higher diffusion rates than culture-grown plants. These studies
      reveal that leaf cell plasmodesmata are dynamic and do not have a set size
      exclusion limit. We also examined targeted movement of the movement protein of
      tobacco mosaic virus fused to GFP, P30::GFP. This 58-kD fusion protein localizes
      to plasmodesmata, consistently transits from up to 78% of transfected cells, and
      was not sensitive to developmental age or growth conditions. The relative number
      of cells containing dilated plasmodesmata varies between different species of
      tobacco, with Nicotiana clevelandii exhibiting greater diffusion of proteins than
      Nicotiana tabacum.

PMID- 11299361
TI  - ANT1, an aromatic and neutral amino acid transporter in Arabidopsis.
AB  - A new amino acid transporter was identified from the Arabidopsis expressed
      sequence tag cDNAs by expressing the cDNA in a yeast amino acid transport mutant.
      Transport analysis of the expressed protein in yeast showed that it transports
      aromatic and neutral amino acids, as well as arginine. This transporter (ANT1,
      aromatic and neutral transporter) also transports indole-3-acetic acid and 2,4
      dichlorophenoxyacetic acid. The cDNA is 1.6 kb in length with an open reading
      frame that codes for a protein with 432 amino acids and a calculated molecular
      mass of 50 kD. Hydropathy analysis showed ANT1 is an integral membrane protein
      with 11 putative membrane-spanning domains. Southern analysis and a BLAST search
      of the Arabidopsis genome database suggests that ANT1 is part of a small gene
      family containing at least five members. Phylogenetic comparisons with other
      known amino acid transporters in plants suggests that ANT1 represents a new class
      of amino acid transporter. RNA gel-blot analysis showed that this transporter is
      expressed in all organs with highest abundance in flowers and cauline leaves.

PMID- 11299362
TI  - Isolation of a CONSTANS ortholog from Pharbitis nil and its role in flowering.
AB  - The short-day plant Pharbitis nil is a model plant for the study of photoperiodic
      control of floral initiation. Flower formation can be induced at the cotyledon
      stage by a single long night of at least 14 h in duration. Using differential
      display of mRNA we identified a P. nil ortholog of the Arabidopsis CONSTANS (CO)
      gene, which will be referred to as PnCO. Expression of PnCO was high after a 14-h
      night, but low when the dark period was 12 h or less. Our results indicate that
      the level of the PnCO transcript is photoperiodically regulated. After transfer
      from continuous light to darkness, PnCO showed a circadian pattern of expression.
      Expression of the CAB gene, which is a molecular marker for the circadian clock,
      exhibited a different pattern of expression than did PnCO and was not subject to
      the same photoperiodic control. A major portion of the PnCO transcripts contained
      an unspliced intron. Only the intron-free PnCO was able to complement the co
      mutant of Arabidopsis by shortening the time to flower.

PMID- 11299363
TI  - A novel dark-inducible protein, LeDI-2, and its involvement in root-specific
      secondary metabolism in Lithospermum erythrorhizon.
AB  - Lithospermum erythrorhizon produces red naphthoquinone pigments that are shikonin
      derivatives. They are accumulated exclusively in the roots of this plant. The
      biosynthesis of shikonin is strongly inhibited by light, even though other
      environmental conditions are optimized. Thus, L. erythrorhizon dark-inducible
      genes (LeDIs) were isolated to investigate the regulatory mechanism of shikonin
      biosynthesis. LeDI-2, showing the strict dark-specific expression, was further
      characterized by use of cell suspension cultures and hairy root cultures as model
      systems. Its mRNA accumulation showed a similar pattern with that of shikonin. In
      the intact plants LeDI-2 expression was observed solely in the root, and the
      longitudinal distribution of its mRNA was also in accordance to that of shikonin.
      LeDI-2 encoded a very hydrophobic polypeptide of 114 amino acids that shared
      significant similarities with some root-specific polypeptides such as ZRP3
      (maize) and RcC3 (rice). Reduction of LeDI-2 expression by its antisense DNA in
      hairy roots of L. erythrorhizon decreased the shikonin accumulation, whereas
      other biosynthetic enzymes, e.g. p-hydroxybenzoic acid:geranyltransferase, which
      catalyzed a critical biosynthetic step, showed similar activity as the wild-type
      clone. This is the first report of the gene that is involved in production of
      secondary metabolites without affecting biosynthetic enzyme activities.

PMID- 11299364
TI  - Unsaturated fatty acids in membrane lipids protect the photosynthetic machinery
      against salt-induced damage in Synechococcus.
AB  - In this study, the tolerance to salt stress of the photosynthetic machinery was
      examined in relation to the effects of the genetic enhancement of the
      unsaturation of fatty acids in membrane lipids in wild-type and desA+ cells of
      Synechococcus sp. PCC 7942. Wild-type cells synthesized saturated and mono
      unsaturated fatty acids, whereas desA+ cells, which had been transformed with the
      desA gene for the Delta12 acyl-lipid desaturase of Synechocystis sp. PCC 6803,
      also synthesized di-unsaturated fatty acids. Incubation of wild-type and desA+
      cells with 0.5 M NaCl resulted in the rapid loss of the activities of photosystem
      I, photosystem II, and the Na+/H+ antiport system both in light and in darkness.
      However, desA+ cells were more tolerant to salt stress and osmotic stress than
      the wild-type cells. The extent of the recovery of the various photosynthetic
      activities from the effects of 0.5 M NaCl was much greater in desA+ cells than in
      wild-type cells. The photosystem II activity of thylakoid membranes from desA+
      cells was more resistant to 0.5 M NaCl than that of membranes from wild-type
      cells. These results demonstrated that the genetically engineered increase in
      unsaturation of fatty acids in membrane lipids significantly enhanced the
      tolerance of the photosynthetic machinery to salt stress. The enhanced tolerance
      was due both to the increased resistance of the photosynthetic machinery to the
      salt-induced damage and to the increased ability of desA+ cells to repair the
      photosynthetic and Na+/H+ antiport systems.

PMID- 11299365
TI  - Light-dependent osmoregulation in pea stem protoplasts. photoreceptors, tissue
      specificity, ion relationships, and physiological implications.
AB  - Light-induced changes in the volume of protoplasts bathed in a medium of constant
      osmolarity are useful indications of light-dependent cellular osmoregulation.
      With this in mind, we investigated the effect of light on the volume of
      protoplasts isolated from the elongating stems of pea (Pisum sativum) seedlings
      raised under red light. The protoplasts were isolated separately from epidermal
      peels and the remaining peeled stems. Under continuous red light, the protoplasts
      of peeled stems swelled steadily, but those of epidermal peels maintained a
      constant volume. Experiments employing far-red light and phytochrome-deficient
      mutants revealed that the observed swelling is a light-induced response mediated
      mainly by phytochromes A and B with a little greater contribution by phytochrome
      A. Protoplasts of epidermal peels and peeled stems shrank transiently in response
      to a pulse of blue light. The blue light responsiveness in this shrinking
      response, which itself is probably mediated by cryptochrome, is under the strict
      control of phytochromes A and B with equal contributions by these phytochromes.
      We suggest that the swelling response participates in the maintenance of high
      tissue tension of elongating stems and that the shrinking response is involved in
      stem growth inhibition. Other findings include the following: The swelling is
      caused by uptake of K+ and Cl-. The presence of Ca2+ in the bathing medium is
      required for phytochrome signaling in the swelling response, but not in the
      response establishing blue light responsiveness. Phytochrome A mediates the two
      responses in a totally red/far-red light reversible manner, as does phytochrome
      B.

PMID- 11299366
TI  - Heritable variation in quinone-induced haustorium development in the parasitic
      plant Triphysaria.
AB  - We are using the facultative hemiparasite, Triphysaria, as a model for studying
      host-parasite signaling in the Scrophulariaceae. Parasitic members of this family
      form subterranean connections, or haustoria, on neighboring host roots to access
      host water and nutrients. These parasitic organs develop in response to
      haustorial-inducing factors contained in host root exudates. A well-characterized
      inducing factor, 2, 6-dimethoxy-p-benzoquinone (DMBQ), can be used to trigger in
      vitro haustorium formation in the roots of Triphysaria. We have assayed three
      species, Triphysaria eriantha (Benth.) Chuang and Heckard, Triphysaria pusilla
      (Benth.) Chuang and Heckard, and Triphysaria versicolor Fischer and C. Meyer, for
      haustorium development in response to DMBQ. There were significant differences
      between the species in their ability to recognize and respond to this quinone.
      Ninety percent of T. versicolor individuals responded, whereas only 40% of T.
      pusilla and less than 10% of T. eriantha formed haustoria. Within field
      collections of self-pollinating T. pusilla, differential responsiveness to DMBQ
      was seen in distinct maternal families. Assaying haustorium development in
      subsequent generations of self-pollinated T. pusilla showed that DMBQ
      responsiveness was heritable. Reciprocal crosses between T. eriantha and T.
      versicolor demonstrated that DMBQ responsiveness was influenced by maternal
      factors. These results demonstrate heritable, natural variation in the
      recognition of a haustorial-inducing factor by a parasitic member of the
      Scrophulariaceae.

PMID- 11299367
TI  - N-acetylglucosamine and glucosamine-containing arabinogalactan proteins control
      somatic embryogenesis.
AB  - In plants, complete embryos can develop not only from the zygote, but also from
      somatic cells in tissue culture. How somatic cells undergo the change in fate to
      become embryogenic is largely unknown. Proteins, secreted into the culture medium
      such as endochitinases and arabinogalactan proteins (AGPs) are required for
      somatic embryogenesis. Here we show that carrot (Daucus carota) AGPs can contain
      glucosamine and N-acetyl-D-glucosaminyl and are sensitive to endochitinase
      cleavage. To determine the relevance of this observation for embryogenesis, an
      assay was developed based on the enzymatic removal of the cell wall from cultured
      cells. The resulting protoplasts had a reduced capacity for somatic
      embryogenesis, which could be partially restored by adding endochitinases to the
      protoplasts. AGPs from culture medium or from immature seeds could fully restore
      or even increase embryogenesis. AGPs pretreated with chitinases were more active
      than untreated molecules and required an intact carbohydrate constituent for
      activity. AGPs were only capable of promoting embryogenesis from protoplasts in a
      short period preceding cell wall reformation. Apart from the increase in
      embryogenesis, AGPs can reinitiate cell division in a subpopulation of otherwise
      non-dividing protoplasts. These results show that chitinase-modified AGPs are
      extracellular matrix molecules able to control or maintain plant cell fate.

PMID- 11299368
TI  - Molecular characterization of tomato 3-dehydroquinate dehydratase-shikimate:NADP
      oxidoreductase.
AB  - Analysis of cDNAs encoding the bifunctional 3-dehydroquinate dehydratase
      shikimate:NADP oxidoreductase (DHQase-SORase) from tomato (Lycopersicon
      esculentum) revealed two classes of cDNAs that differed by 57 bp within the
      coding regions, but were otherwise identical. Comparison of these cDNA sequences
      with the sequence of the corresponding single gene unequivocally proved that the
      primary transcript is differentially spliced, potentially giving rise to two
      polypeptides that differ by 19 amino acids. Quantitative real-time polymerase
      chain reaction revealed that the longer transcript constitutes at most 1% to 2%
      of DHQase-SORase transcripts. Expression of the respective polypeptides in
      Escherichia coli mutants lacking the DHQase or the SORase activity gave
      functional complementation only in case of the shorter polypeptide, indicating
      that skipping of a potential exon is a prerequisite for the production of an
      enzymatically active protein. The deduced amino acid sequence revealed that the
      DHQase-SORase is most likely synthesized as a precursor with a very short (13
      amino acid) plastid-specific transit peptide. Like other genes encoding enzymes
      of the prechorismate pathway in tomato, this gene is elicitor-inducible. Tissue
      specific expression resembles the patterns obtained for 3-deoxy-D-arabino
      heptulosonate 7-phosphate synthase 2 and dehydroquinate synthase genes. This work
      completes our studies of the prechorismate pathway in that cDNAs for all seven
      enzymes (including isozymes) of the prechorismate pathway from tomato have now
      been characterized.

PMID- 11299369
TI  - Induction of a major leaf acid phosphatase does not confer adaptation to low
      phosphorus availability in common bean.
AB  - Acid phosphatase is believed to be important for phosphorus scavenging and
      remobilization in plants, but its role in plant adaptation to low phosphorus
      availability has not been critically evaluated. To address this issue, we
      compared acid phosphatase activity (APA) in leaves of common bean (Phaseolus
      vulgaris) in a phosphorus-inefficient genotype (DOR364), a phosphorus-efficient
      genotype (G19833), and their F(5.10) recombinant inbred lines (RILs). Phosphorus
      deficiency substantially increased leaf APA, but APA was much higher and more
      responsive to phosphorus availability in DOR364 than in G19833. Leaf APA
      segregated in the RILs, with two discrete groups having either high (mean = 1.71
      micromol/mg protein/min) or low (0.36 micromol/mg protein/min) activity. A chi
      square test indicated that the observed difference might be controlled by a
      single gene. Non-denaturing protein electrophoresis revealed that there are four
      visible isoforms responsible for total APA in common bean, and that the
      difference in APA between contrasting genotypes could be attributed to the
      existence of a single major isoform. Qualitative mapping of the APA trait and
      quantitative trait loci analysis with molecular markers indicated that a major
      gene contributing to APA is located on linkage group B03 of the unified common
      bean map. This locus was not associated with loci conferring phosphorus
      acquisition efficiency or phosphorus use efficiency. RILs contrasting for APA had
      similar phosphorus pools in old and young leaves under phosphorus stress, arguing
      against a role for APA in phosphorus remobilization. Our results do not support a
      major role for leaf APA induction in regulating plant adaptation to phosphorus
      deficiency.

PMID- 11299370
TI  - Chloroplast and mitochondrial proteases in Arabidopsis. A proposed nomenclature.
AB  - The identity and scope of chloroplast and mitochondrial proteases in higher
      plants has only started to become apparent in recent years. Biochemical and
      molecular studies suggested the existence of Clp, FtsH, and DegP proteases in
      chloroplasts, and a Lon protease in mitochondria, although currently the full
      extent of their role in organellar biogenesis and function remains poorly
      understood. Rapidly accumulating DNA sequence data, especially from Arabidopsis,
      has revealed that these proteolytic enzymes are found in plant cells in multiple
      isomeric forms. As a consequence, a systematic approach was taken to catalog all
      these isomers, to predict their intracellular location and putative processing
      sites, and to propose a standard nomenclature to avoid confusion and facilitate
      scientific communication. For the Clp protease most of the ClpP isomers are found
      in chloroplasts, whereas one is mitochondrial. Of the ATPase subunits, the one
      ClpD and two ClpC isomers are located in chloroplasts, whereas both ClpX isomers
      are present in mitochondria. Isomers of the Lon protease are predicted in both
      compartments, as are the different forms of FtsH protease. DegP, the least
      characterized protease in plant cells, has the most number of isomers and they
      are predicted to localize in several cell compartments. These predictions, along
      with the proposed nomenclature, will serve as a framework for future studies of
      all four families of proteases and their individual isomers.

PMID- 11299372
TI  - Biosynthesis of germacrene A carboxylic acid in chicory roots. Demonstration of a
      cytochrome P450 (+)-germacrene a hydroxylase and NADP+-dependent sesquiterpenoid
      dehydrogenase(s) involved in sesquiterpene lactone biosynthesis.
AB  - Sprouts of chicory (Cichorium intybus), a vegetable grown in the dark, have a
      slightly bitter taste associated with the presence of guaianolides,
      eudesmanolides, and germacranolides. The committed step in the biosynthesis of
      these compounds is catalyzed by a (+)-germacrene A synthase. Formation of the
      lactone ring is the postulated next step in biosynthesis of the germacrene
      derived sesquiterpene lactones. The present study confirms this hypothesis by
      isolation of enzyme activities from chicory roots that introduce a carboxylic
      acid function in the germacrene A isopropenyl side chain, which is necessary for
      lactone ring formation. (+)-germacrene A is hydroxylated to germacra
      1(10),4,11(13)-trien-12-ol by a cytochrome P450 enzyme, and is subsequently
      oxidized to germacra-1(10),4,11(13)-trien-12-oic acid by NADP+-dependent
      dehydrogenase(s). Both oxidized germacrenes were detected as their Cope
      rearrangement products elema-1,3,11(13)-trien-12-ol and elema-1,3,11(13)-trien-12
      oic acid, respectively. The cyclization products of germacra-1(10),4,11(13)-trien
      12-ol, i.e. costol, were also observed. The (+)-germacrene A hydroxylase is
      inhibited by carbon monoxide (blue-light reversible), has an optimum pH at 8.0,
      and hydroxylates beta-elemene with a modest degree of enantioselectivity.

PMID- 11299371
TI  - Increased sensitivity of photosynthesis to antimycin A induced by inactivation of
      the chloroplast ndhB gene. Evidence for a participation of the NADH-dehydrogenase
      complex to cyclic electron flow around photosystem I.
AB  - Tobacco (Nicotiana tabacum var Petit Havana) ndhB-inactivated mutants (ndhB-)
      obtained by plastid transformation (E.M. Horvath, S.O. Peter, T. Joet, D. Rumeau,
      L. Cournac, G.V. Horvath, T.A. Kavanagh, C. Schafer, G. Peltier, P.
      MedgyesyHorvath [2000] Plant Physiol 123: 1337-1350) were used to study the role
      of the NADH-dehydrogenase complex (NDH) during photosynthesis and particularly
      the involvement of this complex in cyclic electron flow around photosystem I
      (PSI). Photosynthetic activity was determined on leaf discs by measuring CO2
      exchange and chlorophyll fluorescence quenchings during a dark-to-light
      transition. In the absence of treatment, both non-photochemical and photochemical
      fluorescence quenchings were similar in ndhB- and wild type (WT). When leaf discs
      were treated with 5 microM antimycin A, an inhibitor of cyclic electron flow
      around PSI, both quenchings were strongly affected. At steady state, maximum
      photosynthetic electron transport activity was inhibited by 20% in WT and by 50%
      in ndhB-. Under non-photorespiratory conditions (2% O2, 2,500 microL x L(-1)
      CO2), antimycin A had no effect on photosynthetic activity of WT, whereas a 30%
      inhibition was observed both on quantum yield of photosynthesis assayed by
      chlorophyll fluorescence and on CO2 assimilation in ndhB-. The effect of
      antimycin A on ndhB- could not be mimicked by myxothiazol, an inhibitor of the
      mitochondrial cytochrome bc1 complex, therefore showing that it is not related to
      an inhibition of the mitochondrial electron transport chain but rather to an
      inhibition of cyclic electron flow around PSI. We conclude to the existence of
      two different pathways of cyclic electron flow operating around PSI in higher
      plant chloroplasts. One of these pathways, sensitive to antimycin A, probably
      involves ferredoxin plastoquinone reductase, whereas the other involves the NDH
      complex. The absence of visible phenotype in ndhB- plants under normal conditions
      is explained by the complement of these two pathways in the supply of extra-ATP
      for photosynthesis.

PMID- 11299373
TI  - Expression of D-myo-inositol-3-phosphate synthase in soybean. Implications for
      phytic acid biosynthesis.
AB  - Phytic acid, a phosphorylated derivative of myo-inositol, functions as the major
      storage form of phosphorus in plant seeds. Myo-inositol phosphates, including
      phytic acid, play diverse roles in plants as signal transduction molecules,
      osmoprotectants, and cell wall constituents. D-myo-inositol-3-phosphate synthase
      (MIPS EC 5.5.1.4) catalyzes the first step in de novo synthesis of myo-inositol.
      A soybean (Glycine max) MIPS cDNA (GmMIPS1) was isolated by reverse transcriptase
      PCR using consensus primers designed from highly conserved regions in other plant
      MIPS sequences. Southern-blot analysis and database searches indicated the
      presence of at least four MIPS genes in the soybean genome. Northern-blot and
      immunoblot analyses indicated higher MIPS expression and accumulation in immature
      seeds than in other soybean tissues. MIPS was expressed early in the cotyledonary
      stage of seed development. The GmMIPS1 expression pattern suggested that it
      encodes a MIPS isoform that functions in seeds to generate D-myo-inositol-3
      phosphate as a substrate for phytic acid biosynthesis.

PMID- 11299374
TI  - A new protein phosphatase 2C (FsPP2C1) induced by abscisic acid is specifically
      expressed in dormant beechnut seeds.
AB  - An abscisic acid (ABA)-induced cDNA fragment encoding a putative protein
      phosphatase 2C (PP2C) was obtained by means of differential reverse transcriptase
      polymerase chain reaction approach. The full-length clone was isolated from a
      cDNA library constructed using mRNA from ABA-treated beechnut (Fagus sylvatica)
      seeds. This clone presents all the features of plant type PP2C and exhibits
      homology to members of this family such as AthPP2CA (61%), ABI1 (48%), or ABI2
      (47%), therefore it was named FsPP2C1. The expression of FsPP2C1 is detected in
      dormant seeds and increases after ABA treatment, when seeds are maintained
      dormant, but it decreases and tends to disappear when dormancy is being released
      by stratification or under gibberellic acid treatment. Moreover, drought stress
      seems to have no effect on FsPP2C1 transcript accumulation. The FsPP2C1
      transcript expression is tissue specific and was found to accumulate in ABA
      treated seeds rather than in other ABA-treated vegetative tissues examined. These
      results suggest that the corresponding protein could be related to ABA-induced
      seed dormancy. By expressing FsPP2C1 in Escherichia coli as a histidine tag
      fusion protein, we have obtained direct biochemical evidence supporting Mg2+
      dependent phosphatase activity of this protein.

PMID- 11299375
TI  - Phytochrome A mediates blue light and UV-A-dependent chloroplast gene
      transcription in green leaves.
AB  - We characterized the photobiology of light-activated chloroplast transcription
      and transcript abundance in mature primary leaves by using the following two
      systems: transplastomic promoter-reporter gene fusions in tobacco (Nicotiana
      tabacum), and phytochrome (phyA, phyB, and hy2) and cryptochrome (cry1) mutants
      of Arabidopsis. In both dicots, blue light and UV-A radiation were the major
      signals that activated total chloroplast and psbA, rbcL, and 16S rrn
      transcription. In contrast, transcription activities in plants exposed to red and
      far-red light were 30% to 85% less than in blue light/UV-A, depending on the gene
      and plant species. Total chloroplast, psbA, and 16S rrn transcription were 60% to
      80% less in the Arabidopsis phyA mutant exposed to blue light/UV-A relative to
      wild type, thus definitively linking phyA signaling to these photoresponses. To
      our knowledge, the major role of phyA in mediating the blue light/UV-A
      photoresponses is a new function for phyA in chloroplast biogenesis at this stage
      of leaf development. Although rbcL expression in plants exposed to UV-A was 50%
      less in the phyA mutant relative to wild type, blue light-induced rbcL expression
      was not significantly affected in the phyA, phyB, and cry1 mutants. However, rbcL
      expression in blue light was 60% less in the phytochrome chromophore mutant, hy2,
      relative to wild type, indicating that another phytochrome species (phyC, D, or
      E) was involved in blue light-induced rbcL transcription. Therefore, at least two
      different phytochromes, as well as phytochrome-independent photosensory pathways,
      mediated blue light/UV-A-induced transcription of chloroplast genes in mature
      leaves.

PMID- 11299376
TI  - The sucrose analog palatinose leads to a stimulation of sucrose degradation and
      starch synthesis when supplied to discs of growing potato tubers.
AB  - In the present paper we investigated the effect of the sucrose (Suc) analog
      palatinose on potato (Solanum tuberosum) tuber metabolism. In freshly cut discs
      of growing potato tubers, addition of 5 mM palatinose altered the metabolism of
      exogenously supplied [U-14C]Suc. There was slight inhibition of the rate of 14C
      Suc uptake, a 1.5-fold increase in the rate at which 14C-Suc was subsequently
      metabolized, and a shift in the allocation of the metabolized label in favor of
      starch synthesis. The sum result of these changes was a 2-fold increase in the
      absolute rate of starch synthesis. The increased rate of starch synthesis was
      accompanied by a 3-fold increase in inorganic pyrophosphate, a 2-fold increase in
      UDP, decreased UTP/UDP, ATP/ADP, and ATP/AMP ratios, and decreased adenylate
      energy charge, whereas glycolytic and Krebs cycle intermediates were unchanged.
      In addition, feeding palatinose to potato discs also stimulated the metabolism of
      exogenous 14C-glucose in favor of starch synthesis. In vitro studies revealed
      that palatinose is not metabolized by Suc synthases or invertases within potato
      tuber extracts. Enzyme kinetics revealed different effects of palatinose on Suc
      synthase and invertase activities, implicating palatinose as an allosteric
      effector leading to an inhibition of Suc synthase and (surprisingly) to an
      activation of invertase in vitro. However, measurement of tissue palatinose
      levels revealed that these were too low to have significant effects on Suc
      degrading activities in vivo. These results suggest that supplying palatinose to
      potato tubers represents a novel way to increase starch synthesis.

PMID- 11299377
TI  - Possible role of root border cells in detection and avoidance of aluminum
      toxicity.
AB  - Root border cells are living cells that surround root apices of most plant
      species and are involved in production of root exudates. We tested predictions of
      the hypothesis that they participate in detection and avoidance of aluminum (Al)
      toxicity by comparing responses of two snapbean (Phaseolus vulgaris) cultivars
      (cv Dade and cv Romano) known to differ in Al resistance at the whole-root level.
      Root border cells of these cultivars were killed by excess Al in agarose gels or
      in simple salt solutions. Percent viability of Al-sensitive cv Romano border
      cells exposed in situ for 96 h to 200 microM total Al in an agarose gel was
      significantly less than that of cv Dade border cells; similarly, relative
      viability of harvested cv Romano border cells was significantly less than that of
      cv Dade cells after 24 h in 25 microM total Al in a simple salt solution. These
      results indicate that Al-resistance mechanisms that operate at the level of whole
      roots also operate at the cellular level in border cells. Al induced a thicker
      mucilage layer around detached border cells of both cultivars. Cultivar Dade
      border cells produced a thicker mucilage layer in response to 25 microM Al
      compared with that of cv Romano cells after 8 h of treatment and this phenomenon
      preceded that of observed cultivar differences in relative cell viability.
      Release of an Al-binding mucilage by border cells could play a role in protecting
      root tips from Al-induced cellular damage.

PMID- 11299378
TI  - Regulation of psbA and psaE expression by light quality in Synechocystis species
      PCC 6803. A redox control mechanism.
AB  - We investigated the influence of light of different wavelengths on the expression
      of the psbA gene, which encodes the D1 protein of the photosystem II and the psaE
      gene, which encodes the subunit Psa-E of the photosystem I, in Synechocystis sp
      PCC 6803. In an attempt to differentiate between a light-sensory and a redox
      sensory signaling processes, the effect of orange, blue, and far-red light was
      studied in the wild-type and in a phycobilisome-less mutant. Transferring wild
      type cells from one type of illumination to another induced changes in the redox
      state of the electron transport chain and in psbA and psaE expression. Blue and
      far-red lights (which are preferentially absorbed by the photosystem I) induced
      an accumulation of psbA transcripts and a decrease of the psaE mRNA level. In
      contrast, orange light (which is preferentially absorbed by the photosystem II)
      induced a large accumulation of psaE transcripts and a decrease of psbA mRNA
      level. Transferring mutant cells from blue to orange light (or vice versa) had no
      effect either on the redox state of the electron transport chain or on the levels
      of psbA and psaE mRNAs. Thus, light quality seems to regulate expression of these
      genes via a redox sensory mechanism in Synechocystis sp PCC 6803 cells. Our data
      suggest that the redox state of one of the electron carriers between the
      plastoquinone pool and the photosystem I has opposite influences on psbA and psaE
      expression. Its reduction induces accumulation of psaE transcripts, and its
      oxidation induces accumulation of psbA mRNAs.

PMID- 11299379
TI  - Isoprene increases thermotolerance of fosmidomycin-fed leaves.
AB  - Isoprene is synthesized and emitted in large amounts by a number of plant
      species, especially oak (Quercus sp.) and aspen (Populus sp.) trees. It has been
      suggested that isoprene improves thermotolerance by helping photosynthesis cope
      with high temperature. However, the evidence for the thermotolerance hypothesis
      is indirect and one of three methods used to support this hypothesis has recently
      been called into question. More direct evidence required new methods of
      controlling endogenous isoprene. An inhibitor of the deoxyxylulose 5-phosphate
      pathway, the alternative pathway to the mevalonic acid pathway and the pathway by
      which isoprene is made, is now available. Fosmidomycin eliminates isoprene
      emission without affecting photosynthesis for several hours after feeding to
      detached leaves. Photosynthesis of fosmidomycin-fed leaves recovered less
      following a 2-min high-temperature treatment at 46 degrees C than did
      photosynthesis of leaves fed water or fosmidomycin-fed leaves in air supplemented
      with isoprene. Photosynthesis of Phaseolus vulgaris leaves, which do not make
      isoprene, exhibited increased thermotolerance when isoprene was supplied in the
      airstream flowing over the leaf. Other short-chain alkenes also improved
      thermotolerance, whereas alkanes reduced thermotolerance. It is concluded that
      thermotolerance of photosynthesis is a substantial benefit to plants that make
      isoprene and that this benefit explains why plants make isoprene. The effect may
      be a general hydrocarbon effect and related to the double bonds in the isoprene
      molecule.

PMID- 11299380
TI  - Active oxygen produced during selective excitation of photosystem I is damaging
      not only to photosystem I, but also to photosystem II.
AB  - With the aim to specifically study the molecular mechanisms behind
      photoinhibition of photosystem I, stacked spinach (Spinacia oleracea) thylakoids
      were irradiated at 4 degrees C with far-red light (>715 nm) exciting photosystem
      I, but not photosystem II. Selective excitation of photosystem I by far-red light
      for 130 min resulted in a 40% inactivation of photosystem I. It is surprising
      that this treatment also caused up to 90% damage to photosystem II. This suggests
      that active oxygen produced at the reducing side of photosystem I is highly
      damaging to photosystem II. Only a small pool of the D1-protein was degraded.
      However, most of the D1-protein was modified to a slightly higher molecular mass,
      indicative of a damage-induced conformational change. The far-red illumination
      was also performed using destacked and randomized thylakoids in which the
      distance between the photosystems is shorter. Upon 130 min of illumination,
      photosystem I showed an approximate 40% inactivation as in stacked thylakoids. In
      contrast, photosystem II only showed 40% inactivation in destacked and randomized
      thylakoids, less than one-half of the inactivation observed using stacked
      thylakoids. In accordance with this, photosystem II, but not photosystem I is
      more protected from photoinhibition in destacked thylakoids. Addition of active
      oxygen scavengers during the far-red photosystem I illumination demonstrated
      superoxide to be a major cause of damage to photosystem I, whereas photosystem II
      was damaged mainly by superoxide and hydrogen peroxide.

PMID- 11299381
TI  - Brassicaceae express multiple isoforms of biotin carboxyl carrier protein in a
      tissue-specific manner.
AB  - Plastidial acetyl-coenzyme A carboxylase from most plants is a multi-enzyme
      complex comprised of four different subunits. One of these subunits, the biotin
      carboxyl carrier protein (BCCP), was previously proposed to be encoded by a
      single gene in Arabidopsis. We report and characterize here a second Arabidopsis
      BCCP (AtBCCP2) cDNA with 42% amino acid identity to AtBCCP1 and 75% identity to a
      class of oilseed rape (Brassica napus) BCCPs. Both Arabidopsis BCCP isoforms were
      expressed in Escherichia coli and found to be biotinylated and supported
      carboxylation activity when reconstituted with purified, recombinant Arabidopsis
      biotin carboxylase. In vitro translated AtBCCP2 was competent for import into pea
      (Pisum sativum) chloroplasts and processed to a 25-kD polypeptide. Extracts of
      Arabidopsis seeds contained biotinylated polypeptides of 35 and 25 kD, in
      agreement with the masses of recombinant AtBCCP1 and 2, respectively. AtBCCP1
      protein was present in developing tissues from roots, leaves, flowers, siliques,
      and seeds, whereas AtBCCP2 protein was primarily expressed in 7 to 10 d-after
      flowering seeds at levels approximately 2-fold less abundant than AtBCCP1.
      AtBCCP1 transcript reflected these protein expression profiles present in all
      developing organs and highest in 14-d leaves and siliques, whereas AtBCCP2
      transcript was present in flowers and siliques. In protein blots, four different
      BCCP isoforms were detected in developing seeds from oilseed rape. Of these, a 35
      kD BCCP was detected in immature leaves and developing seeds, whereas developing
      seeds also contained 22-, 25-, and 37-kD isoforms highly expressed 21 d after
      flowering. These data indicate that oilseed plants in the family Brassicaceae
      contain at least one to three seed-up-regulated BCCP isoforms, depending upon
      genome complexity.

PMID- 11299382
TI  - Function and dynamics of auxin and carbohydrates during earlywood/latewood
      transition in scots pine.
AB  - In temperate regions the annual pattern of wood development is characterized by
      the formation of radially narrow and thick walled latewood cells. This takes
      place at the later part of the growing season when cambial cell division
      declines. To gain new insight into the regulation of this process, micro
      analytical techniques were used to visualize the distribution of indole-3-acetic
      acid (IAA), soluble carbohydrates, and activities of sucrose (Suc)-metabolizing
      enzymes across the cambial region tissues in Scots pine (Pinus sylvestris). The
      total amount of IAA in the cambial region did not change with latewood
      initiation. But its radial distribution pattern was altered, resulting in an
      increased concentration in the cambial meristem and its recent derivatives. Thus,
      initiation of latewood formation and cessation of cambial cell division is not a
      consequence of decreased IAA concentrations in dividing and expanding cells.
      Rather, IAA most likely has a role in defining the altered developmental pattern
      associated with latewood formation. Carbohydrates and enzyme activities showed
      distinctive radial distribution patterns. Suc peaked in the phloem and decreased
      sharply to low levels across the cambial zone, whereas fructose and glucose
      reached their highest levels in the maturing tracheids. Suc synthase was the
      dominating Suc cleaving enzyme with a peak in the secondary wall-forming
      tracheids and in the phloem. Soluble acid invertase peaked in dividing and
      expanding cells. Suc-phosphate synthase had its highest activities in the phloem.
      Activities of cell wall bound invertase were low. The absence of major seasonal
      variations indicates that carbohydrate availability is not a trigger for latewood
      initiation. However, steep concentration gradients of the sugars suggest a role
      for sugar signaling in vascular development.

PMID- 11299383
TI  - Pollen tubes of Nicotiana alata express two genes from different beta-glucan
      synthase families.
AB  - The walls deposited by growing pollen tubes contain two types of beta-glucan, the
      (1,3)-beta-glucan callose and the (1,4)-beta-glucan cellulose, as well as various
      alpha-linked pectic polysaccharides. Pollen tubes of Nicotiana alata Link et
      Otto, an ornamental tobacco, were therefore used to identify genes potentially
      encoding catalytic subunits of the callose synthase and cellulose synthase
      enzymes. Reverse transcriptase-polymerase chain reactions (RT-PCR) with pollen
      tube RNA and primers designed to conserved regions of bacterial and plant
      cellulose synthase (CesA) genes amplified a fragment that corresponded to an
      abundantly expressed cellulose-synthase-like gene named NaCslD1. A fragment from
      a true CesA gene (NaCesA1) was also amplified, but corresponding cDNAs could not
      be identified in a pollen-tube library, consistent with the very low level of
      expression of the NaCesA1 gene. RT-PCR with pollen-tube RNA and primers designed
      to regions conserved between the fungal FKS genes [that encode (1,3)-beta-glucan
      synthases] and their presumed plant homologs (the Gsl or glucan-synthase-like
      genes) amplified a fragment that corresponded to an abundantly expressed gene
      named NaGsl1. A second Gsl gene detected by RT-PCR (NaGsl2) was expressed at low
      levels in immature floral organs. The structure of full-length cDNAs of NaCslD1,
      NaCesA1, and NaGsl1 are presented. Both NaCslD1 and NaGsl1 are predominantly
      expressed in the male gametophyte (developing and mature pollen and growing
      pollen tubes), and we propose that they encode the catalytic subunits of two beta
      glucan synthases involved in pollen-tube wall synthesis. Different beta-glucans
      deposited in one cell type may therefore be synthesized by enzymes from different
      gene families.

PMID- 11299384
TI  - Azospirillum brasilense and Azospirillum lipoferum hydrolyze conjugates of GA20
      and metabolize the resultant aglycones to GA1 in seedlings of rice dwarf mutants.
AB  - Azospirillum species are plant growth-promotive bacteria whose beneficial effects
      have been postulated to be partially due to production of phytohormones,
      including gibberellins (GAs). In this work, Azospirillum brasilense strain Cd and
      Azospirillum lipoferum strain USA 5b promoted sheath elongation growth of two
      single gene GA-deficient dwarf rice (Oryza sativa) mutants, dy and dx, when the
      inoculated seedlings were supplied with [17,17-2H2]GA20-glucosyl ester or [17,17-
      2H2]GA20-glucosyl ether. Results of capillary gas chromatography-mass
      spectrometry analysis show that this growth was due primarily to release of the
      aglycone [17,17-2H2]GA20 and its subsequent 3beta-hydroxylation to [17,17-2H2]GA1
      by the microorganism for the dy mutant, and by both the rice plant and
      microorganism for the dx mutant.

PMID- 11299385
TI  - Expression of a Pseudomonas aeruginosa citrate synthase gene in tobacco is not
      associated with either enhanced citrate accumulation or efflux.
AB  - Aluminum (Al) toxicity and poor phosphorus (P) availability are factors that
      limit plant growth on many agricultural soils. Previous work reported that
      expression of a Pseudomonas aeruginosa citrate synthase gene in tobacco
      (Nicotiana tabacum; CSb lines) resulted in improved Al tolerance (J.M. de la
      Fuente, V. Ramirez-Rodriguez, J.L. Cabrera-Ponce, L. Herrera-Estrella [1997]
      Science 276: 1566-1568) and an enhanced ability to acquire P from alkaline soils
      (J. Lopez-Bucio, O. Martinez de la Vega, A. Guevara-Garcia, L. Herrera-Estrella
      [2000] Nat Biotechnol 18: 450-453). These effects were attributed to the P.
      aeruginosa citrate synthase increasing the biosynthesis and efflux of citrate
      from roots. To verify these findings we: (a) characterized citrate efflux from
      roots of wild-type tobacco; (b) generated tobacco lines expressing the citrate
      synthase gene from P. aeruginosa; and (c) analyzed selected CSb lines described
      above. Al stimulated citrate efflux from intact roots of wild-type tobacco and
      root apices were found to be responsible for most of the efflux. Despite
      generating transgenic tobacco lines that expressed the citrate synthase protein
      at up to a 100-fold greater level than the previously described CSb lines, these
      lines did not show increased accumulation of citrate in roots or increased Al
      activated efflux of citrate from roots. Selected CSb lines, similarly, failed to
      show differences compared with controls in either citrate accumulation or efflux.
      We conclude that expression of the P. aeruginosa citrate synthase gene in plants
      is unlikely to be a robust and easily reproducible strategy for enhancing the Al
      tolerance and P-nutrition of crop and pasture species.

PMID- 11299386
TI  - Induction of vacuolar ATPase and mitochondrial ATP synthase by aluminum in an
      aluminum-resistant cultivar of wheat.
AB  - Two 51-kD aluminum (Al)-induced proteins (RMP51, root membrane proteins of 51 kD)
      were recently discovered in an aluminum-resistant cultivar of wheat (Triticum
      aestivum) cv PT741 (Basu et al., 1994a). These proteins segregate with the
      aluminum resistance phenotype in a segregating population arising from a cross
      between Al-resistant cv PT741 and Al-sensitive cv Katepwa (Taylor et al., 1997).
      The proteins have been purified by continuous elution electrophoresis and
      analyzed by peptide microsequencing. Sequence analysis of the purified peptides
      revealed that they are homologous to the B subunit of the vacuolar H+-ATPase (V
      ATPase) and the alpha- and beta-subunits of the mitochondrial ATP synthase (F1F0
      ATPase). To confirm that these ATPases are induced by Al, ATPase activity and
      transcript levels were analyzed under Al stress. Both V-ATPase and F1F0-ATPase
      activities were induced by Al and responded in a dose-dependent manner to 0 to
      150 microM Al. In contrast, plasma membrane H+-ATPase (P-ATPase) activity
      decreased to 0.5x control levels, even when plants were exposed to 25 microM Al.
      Northern analysis showed that the transcript encoding the B subunit of V-ATPase
      increased by 2.2x in a dose-dependent manner, whereas levels of the transcript
      encoding the alpha-subunit of F1F0-ATPase remained constant. The effect of Al on
      ATPase activity in other cultivars was also examined. The Al-resistant cultivar,
      cv PT741, was the only cultivar to show induction of V- and F1F0-ATPases. These
      results suggest that the V-ATPase in cv PT741 is responding specifically to Al
      stress with the ATP required for its activity supplied by ATP synthase to
      maintain energy balance within the cell.

PMID- 11299387
TI  - Different pathways are involved in phosphate and iron stress-induced alterations
      of root epidermal cell development.
AB  - Low bioavailability of phosphorus (P) and iron (Fe) induces morphogenetic changes
      in roots that lead to a higher surface-to-volume ratio. In Arabidopsis, an
      enlargement in the absorptive surface area is achieved by an increase in the
      length and frequency of hairs in roots of Fe- and P-deficient plants. The extra
      root hairs are often located in positions that are occupied with non-hair cells
      under normal conditions, i.e. over a tangential wall of underlying cortical
      cells. An involvement of auxin and ethylene in root epidermis cell development of
      Fe- and P-deficient plants was inferred from phenotypical analysis of hormone
      related Arabidopsis mutants and from the application of substances that interfere
      with either synthesis, transport, or perception of the hormones. Application of
      the ethylene precursor 1-aminocyclopropane-1-carboxylic acid or the auxin analog
      2,4-D caused a marked increase in root hair density in plants of all growth types
      and confers a phenotype characteristic of ethylene-overproducing mutants. Hormone
      insensitivity and application of hormone antagonists inhibited the initiation of
      extranumerary root hairs induced by Fe deficiency, but did not counteract the
      formation of extra hairs in response to P deprivation. A model is presented
      summarizing putative pathways for alterations in root epidermal cell patterning
      induced by environmental stress.

PMID- 11299388
TI  - Amyloplasts that sediment in protonemata of the moss Ceratodon purpureus are
      nonrandomly distributed in microgravity.
AB  - Little is known about whether or how plant cells regulate the position of heavy
      organelles that sediment toward gravity. Dark-grown protonemata of the moss
      Ceratodon purpureus displays a complex plastid zonation in that only some
      amyloplasts sediment along the length of the tip cell. If gravity is the major
      force determining the position of amyloplasts that sediment, then these plastids
      should be randomly distributed in space. Instead, amyloplasts were clustered in
      the subapical region in microgravity. Cells rotated on a clinostat on earth had a
      roughly similar non-random plastid distribution. Subapical clusters were also
      found in ground controls that were inverted and kept stationary, but the
      distribution profile differed considerably due to amyloplast sedimentation. These
      findings indicate the existence of as yet unknown endogenous forces and
      mechanisms that influence amyloplast position and that are normally masked in
      stationary cells grown on earth. It is hypothesized that a microtubule-based
      mechanism normally compensates for g-induced drag while still allowing for
      regulated amyloplast sedimentation.

PMID- 11299389
TI  - A pollen coat protein, SP11/SCR, determines the pollen S-specificity in the self
      incompatibility of Brassica species.
AB  - Many flowering plants have evolved self-incompatibility (SI) systems to prevent
      inbreeding. In the Brassicaceae, SI is genetically controlled by a single
      polymorphic locus, termed the S-locus. Pollen rejection occurs when stigma and
      pollen share the same S-haplotype. Recognition of S-haplotype specificity has
      recently been shown to involve at least two S-locus genes, S-receptor kinase
      (SRK) and S-locus protein 11 or S-locus Cys-rich (SP11/SCR). SRK encodes a
      polymorphic membrane-spanning protein kinase, which is the sole female
      determinant of the S-haplotype specificity. SP11/SCR encodes a highly polymorphic
      Cys-rich small basic protein specifically expressed in the anther tapetum and in
      pollen. In cauliflower (B. oleracea), the gain-of-function approach has
      demonstrated that an allele of SP11/SCR encodes the male determinant of S
      specificity. Here we examined the function of two alleles of SP11/SCR of B. rapa
      by the same approach and further established that SP11/SCR is the sole male
      determinant of SI in the genus Brassica sp. Our results also suggested that the
      522-bp 5'-upstream region of the S9-SP11 gene used to drive the transgene
      contained all the regulatory elements required for the unique
      sporophytic/gametophytic expression observed for the native SP11 gene. Promoter
      deletion analyses suggested that the highly conserved 192-bp upstream region was
      sufficient for driving this unique expression. Furthermore, immunohistochemical
      analyses revealed that the protein product of the SP11 transgene was present in
      the tapetum and pollen, and that in pollen of late developmental stages, the SP11
      protein was mainly localized in the pollen coat, a finding consistent with its
      expected biological role.

PMID- 11299390
TI  - Differential regulation of a family of apyrase genes from Medicago truncatula.
AB  - Four putative apyrase genes were identified from the model legume Medicago
      truncatula. Two of the genes identified from M. truncatula (Mtapy1 and Mtapy4)
      are expressed in roots and are inducible within 3 h after inoculation with
      Sinorhizobium meliloti. The level of mRNA expression of the other two putative
      apyrases, Mtapy2 and Mtapy3, was unaffected by rhizobial inoculation. Screening
      of a bacterial artificial chromosome library of M. truncatula genomic DNA showed
      that Mtapy1, Mtapy3, and Mtapy4 are present on a single bacterial artificial
      chromosome clone. This apyrase cluster was mapped to linkage group seven. A
      syntenic region on soybean linkage group J was found to contain at least two
      apyrase genes. Screening of nodulation deficient mutants of M. truncatula
      revealed that two such mutants do not express apyrases to any detectable level.
      The data suggest a role for apyrases early in the nodulation response before the
      involvement of root cortical cell division leading to the nodule structure.

PMID- 11299391
TI  - Abscisic acid-induced actin reorganization in guard cells of dayflower is
      mediated by cytosolic calcium levels and by protein kinase and protein
      phosphatase activities.
AB  - In guard cells of open stomata under daylight, long actin filaments are arranged
      at the cortex, radiating out from the stomatal pore. Abscisic acid (ABA), a
      signal for stomatal closure, induces rapid depolymerization of cortical actin
      filaments and the slower formation of a new type of actin that is randomly
      oriented throughout the cell. This change in actin organization has been
      suggested to be important in signaling pathways involved in stomatal closing
      movement, since actin antagonists interfere with normal stomatal closing
      responses to ABA. Here we present evidence that the actin changes induced by ABA
      in guard cells of dayflower (Commelina communis) are mediated by cytosolic
      calcium levels and by protein phosphatase and protein kinase activities.
      Treatment of guard cells with CaCl2 induced changes in actin organization similar
      to those induced by ABA. Removal of extracellular calcium with EGTA inhibited ABA
      induced actin changes. These results suggest that Ca2+ acts as a signal mediator
      in actin reorganization during guard cell response to ABA. A protein kinase
      inhibitor, staurosporine, inhibited actin reorganization in guard cells treated
      with ABA or CaCl2, and also increased the population of cells with long radial
      cortical actin filaments in untreated control cells. A protein phosphatase
      inhibitor, calyculin A, induced fragmentation of actin filaments in ABA- or CaCl2
      treated cells and in control cells, and inhibited the formation of randomly
      oriented long actin filaments induced by ABA or CaCl2. These results suggest that
      protein kinase(s) and phosphatase(s) participate in actin remodeling in guard
      cells during ABA-induced stomatal closure.

PMID- 11299392
TI  - Mobilization of Ca2+ by cyclic ADP-ribose from the endoplasmic reticulum of
      cauliflower florets.
AB  - The NAD+ metabolite cADP-Rib (cADPR) elevates cytosolic free Ca2+ in plants and
      thereby plays a central role in signal transduction pathways evoked by the
      drought and stress hormone abscisic acid. cADPR is known to mobilize Ca2+ from
      the large vacuole of mature cells. To determine whether additional sites for
      cADPR-gated Ca2+ release reside in plant cells, microsomes from cauliflower
      (Brassica oleracea) inflorescences were subfractionated on sucrose density
      gradients, and the distribution of cADPR-elicited Ca2+ release was monitored.
      cADPR-gated Ca2+ release was detected in the heavy-density fractions associated
      with rough endoplasmic reticulum (ER). cADPR-dependent Ca2+ release co-migrated
      with two ER markers, calnexin and antimycin A-insensitive NADH-cytochrome c
      reductase activity. To investigate the possibility that contaminating plasma
      membrane in the ER-rich fractions was responsible for the observed release,
      plasma membrane vesicles were purified by aqueous two-phase partitioning, everted
      with Brij-58, and loaded with Ca2+: These vesicles failed to respond to cADPR.
      Ca2+ release evoked by cADPR at the ER was fully inhibited by ruthenium red and 8
      NH2-cADPR, a specific antagonist of cADPR-gated Ca2+ release in animal cells. The
      presence of a Ca2+ release pathway activated by cADPR at higher plant ER
      reinforces the notion that, alongside the vacuole, the ER participates in Ca2+
      signaling.

PMID- 11299393
TI  - Transgenic manipulation of the metabolism of polyamines in poplar cells.
AB  - The metabolism of polyamines (putrescine, spermidine, and spermine) has become
      the target of genetic manipulation because of their significance in plant
      development and possibly stress tolerance. We studied the polyamine metabolism in
      non-transgenic (NT) and transgenic cells of poplar (Populus nigra x maximowiczii)
      expressing a mouse Orn decarboxylase (odc) cDNA. The transgenic cells showed
      elevated levels of mouse ODC enzyme activity, severalfold higher amounts of
      putrescine, a small increase in spermidine, and a small reduction in spermine as
      compared with NT cells. The conversion of labeled ornithine (Orn) into putrescine
      was significantly higher in the transgenic than the NT cells. Whereas exogenously
      supplied Orn caused an increase in cellular putrescine in both cell lines,
      arginine at high concentrations was inhibitory to putrescine accumulation. The
      addition of urea and glutamine had no effect on polyamines in either of the cell
      lines. Inhibition of glutamine synthetase by methionine sulfoximine led to a
      substantial reduction in putrescine and spermidine in both cell lines. The
      results show that: (a) Transgenic expression of a heterologous odc gene can be
      used to modulate putrescine metabolism in plant cells, (b) accumulation of
      putrescine in high amounts does not affect the native arginine decarboxylase
      activity, (c) Orn biosynthesis occurs primarily from glutamine/glutamate and not
      from catabolic breakdown of arginine, (d) Orn biosynthesis may become a limiting
      factor for putrescine production in the odc transgenic cells, and (e)
      assimilation of nitrogen into glutamine keeps pace with an increased demand for
      its use for putrescine production.

PMID- 11299394
TI  - Maize non-photosynthetic ferredoxin precursor is mis-sorted to the intermembrane
      space of chloroplasts in the presence of light.
AB  - Preprotein translocation across the outer and inner envelope membranes of
      chloroplasts is an energy-dependent process requiring ATP hydrolysis. Several
      precursor proteins analyzed so far have been found to be imported into isolated
      chloroplasts equally well in the dark in the presence of ATP as in the light
      where ATP is supplied by photophosphorylation in the chloroplasts themselves. We
      demonstrate here that precursors of two maize (Zea mays L. cv Golden Cross
      Bantam) ferredoxin isoproteins, pFdI and pFdIII, show distinct characteristics of
      import into maize chloroplasts. pFdI, a photosynthetic ferredoxin precursor, was
      efficiently imported into the stroma of isolated maize chloroplasts both in the
      light and in the dark. In contrast pFdIII, a non-photosynthetic ferredoxin
      precursor, was mostly mis-sorted to the intermembrane space of chloroplastic
      envelopes as an unprocessed precursor form in the light but was efficiently
      imported into the stroma and processed to its mature form in the dark. The mis
      sorted pFdIII, which accumulated in the intermembrane space in the light, could
      not undergo subsequent import into the stroma in the dark, even in the presence
      of ATP. However, when the mis-sorted pFdIII was recovered and used for a separate
      import reaction, pFdIII was capable of import into the chloroplasts in the dark.
      pFNRII, a ferredoxin-NADP+ reductase isoprotein precursor, showed import
      characteristics similar to those of pFdIII. Moreover, pFdIII exhibited similar
      import characteristics with chloroplasts isolated from wheat (Pennisetum
      americanum) and pea (Pisum sativum cv Alaska). These findings suggest that the
      translocation of precursor proteins across the envelope membranes of chloroplasts
      may involve substrate-dependent light-regulated mechanisms.

PMID- 11299395
TI  - Evidence for the involvement of an oxidative stress in the initiation of
      infection of pear by Erwinia amylovora.
AB  - Involvement of an oxidative burst, usually related to incompatible plant/pathogen
      interactions leading to hypersensitive reactions, was investigated with Erwinia
      amylovora, the causal agent of fire blight of Maloideae subfamily of Rosaceae, in
      interaction with pear (Pyrus communis; compatible situation) and tobacco
      (Nicotiana tabacum; incompatible situation). As expected, this necrogenic
      bacterium induced in tobacco a sustained production of superoxide anion, lipid
      peroxidation, electrolyte leakage, and concomitant increases of several
      antioxidative enzymes (ascorbate peroxidases, glutathion reductases, glutathion-S
      transferases, and peroxidases), in contrast to the compatible pathogen
      Pseudomonas syringae pv tabaci, which did not cause such reactions. In pear
      leaves, however, inoculations with both the disease- and the hypersensitive
      reaction-inducing bacteria (E. amylovora and P. syringae pv tabaci, respectively)
      resulted in superoxide accumulation, lipid peroxidation, electrolyte leakage, and
      enzyme induction at similar rates and according to equivalent time courses. The
      unexpected ability of E. amylovora to generate an oxidative stress even in
      compatible situation was linked to its functional hrp (for hypersensitive
      reaction and pathogenicity) cluster because an Hrp secretion mutant of the
      bacteria did not induce any plant response. It is suggested that E. amylovora
      uses the production of reactive oxygen species as a tool to provoke host cell
      death during pathogenesis to invade plant tissues. The bacterial
      exopolysaccharide could protect this pathogen against the toxic effects of oxygen
      species since a non-capsular mutant of E. amylovora induced locally the same
      responses than the wild type but was unable to further colonize the plant.

PMID- 11299396
TI  - Does growth correlate with turgor-induced elastic strain in stems? A re
      evaluation of de Vries' classical experiments.
AB  - The correlation between growth and turgor-induced elastic expansion was studied
      in hypocotyls of sunflower (Helianthus annuus) seedlings under various growth
      conditions. Turgor-induced elastic cell wall strain was greater in hypocotyls of
      faster growing seedlings, i.e. in etiolated versus light-grown ones. It also was
      higher in rapidly growing young seedlings as compared with nongrowing mature
      ones. However, analysis of the spatial distribution of elastic strain and growth
      demonstrated that their correspondence was only apparent. Profiles of elastic
      strain declined steadily from the top of the hypocotyls toward the basis, whereas
      the profiles of relative elemental growth rate along the hypocotyls showed maxima
      within the growing zones. In contrast to earlier hypotheses, we conclude that
      turgor-induced elastic cell wall strain and growth do not correlate precisely in
      growing hypocotyls.

PMID- 11299397
TI  - Class III pistil-specific extensin-like proteins from tobacco have
      characteristics of arabinogalactan proteins.
AB  - Class III pistil-specific extensin-like proteins (PELPIII) are specifically
      localized in the intercellular matrix of tobacco (Nicotiana tabacum) styles.
      After pollination the majority of PELPIII are translocated into the callosic
      layer and the callose plugs of the pollen tubes, which could suggest a function
      of PELPIII in pollen tube growth. PELPIII may represent one of the chemical
      and/or physical factors from the female sporophytic tissue that contributes to
      the difference between in vivo and in vitro pollen tube growth. PELPIII
      glycoproteins were purified and biochemically characterized. Because of their
      high proline (Pro) and hydroxy-Pro (Hyp) content, PELPIII proteins belong to the
      class of Pro/Hyp-rich glycoproteins. The carbohydrate moiety of PELPIII is
      attached through O-glycosidic linkages and comprises more than one-half the total
      glycoprotein. Deglycosylation of PELPIII revealed two backbones, both reacting
      with PELPIII-specific antibodies. N-terminal amino acid sequencing of these
      backbones showed that PELPIII is encoded by the MG14 and MG15 genes. Two
      heterogeneous N-terminal sequences of MG14 and MG15, both starting downstream of
      the predicted signal peptide cleavage site, seem to be present, which indicates a
      novel N-terminal processing. Monosaccharide analysis showed that the carbohydrate
      moiety of PELPIII almost completely consists of arabinose and galactose in an
      equal molar ratio. Carbohydrate linkage analysis showed terminal and 2-linked
      arabinofuranosyl residues, as well as terminal and 6-, 3-, and 3,6-linked
      galactopyranosyl residues to be present, indicating the presence of both extensin
      like and Type II arabinogalactan oligosaccharide units. The ability of beta
      glucosyl Yariv reagent to bind with PELPIII confirmed the arabinogalactan protein
      like characteristics of these proteins.

PMID- 11299398
TI  - Molecular interactions between the specialist herbivore Manduca sexta
      (Lepidoptera, Sphingidae) and its natural host Nicotiana attenuata. IV. Insect
      Induced ethylene reduces jasmonate-induced nicotine accumulation by regulating
      putrescine N-methyltransferase transcripts.
AB  - Attack by the specialist herbivore, Manduca sexta, on its native host Nicotiana
      attenuata Torr. ex Wats. produces a dramatic ethylene release, a jasmonate burst,
      and a suppression of the nicotine accumulation that results from careful
      simulations of the herbivore's damage. Methyl-jasmonate (MeJA) treatment induces
      nicotine biosynthesis. However, this induction can be suppressed by ethylene as
      pretreatment of plants with 1-methylcyclopropene (1-MCP), a competitive inhibitor
      of ethylene receptors, restores the full MeJA-induced nicotine response in
      herbivore attacked plants (J. Kahl, D.H. Siemens, R.J. Aerts, R. Gabler, F.
      Kuhnemann, C.A. Preston, I.T. Baldwin [2000] Planta 210: 336-342). To understand
      whether this herbivore-induced signal cross-talk occurs at the level of
      transcript accumulation, we cloned the putrescine methyltransferase genes (NaPMT1
      and NaPMT2) of N. attenuata, which are thought to represent the rate limiting
      step in nicotine biosynthesis, and measured transcript accumulations by northern
      analysis after various jasmonate, 1-MCP, ethephon, and herbivory treatments.
      Transcripts of both root putrescine N-methyltransferase (PMT) genes and nicotine
      accumulation increased dramatically within 10 h of shoot MeJA treatment and
      immediately after root treatments. Root ethephon treatments suppressed this
      response, which could be reversed by 1-MCP pretreatment. Moreover, 1-MCP
      pretreatment dramatically amplified the transcript accumulation resulting from
      both wounding and M. sexta herbivory. We conclude that attack from this nicotine
      tolerant specialist insect causes N. attenuata to produce ethylene, which
      directly suppresses the nitrogen-intensive biosynthesis of nicotine.

PMID- 11299399
TI  - Laparoscopic colectomy. Where do we stand?
AB  - Laparoscopy has changed our approach to surgery, instrumentation and training.
      The techniques are evolving for a wide range of surgical procedures outside the
      biliary tree. Currently available data suggests that laparoscopic colectomy can
      be completed safely in most cases. It is feasible and offers patient-related
      benefits similar to those described for other laparoscopic procedures. The
      advisability of performing laparoscopy for cure of colorectal malignancy has been
      challenged because the recurrence rates and overall cure rates remain unknown.
      Until prospective randomized trials resolve these issues neoplastic colon
      laparoscopic surgery must be the prerogative of selected and specialized centers.

PMID- 11299400
TI  - Familial Mediterranean Fever.
AB  - Familial Mediterranean Fever is a genetic disorder frequently diagnosed among the
      Arabs. It is also prevalent among Jews, Armenians and Turks. The clinical picture
      consists of febrile and painful attacks that differ in quality across patients
      and even within the same patient. There may be accompanying joint pain, chest
      pain, skin manifestations and other findings, and amyloidosis may occur in some
      patients as a complication. The primary treatment is Colchicine, which decreases
      the frequency of the attacks and prevents the occurrence of amyloidosis. The gene
      responsible for Familial Mediterranean Fever, MEFV, has been mapped and cloned
      and mutations were identified within its coding sequence. It encodes a protein
      that is expected to be a down regulator of inflammation. The spectrum of
      mutations in the Arabic population is partially studied. There are still several
      issues to be solved before we fully understand the disorder, and to enable us to
      confront it and decrease the morbidity and mortality inflicted by it.

PMID- 11299401
TI  - Pattern of breast diseases in a teaching hospital in Jeddah, Saudi Arabia.
AB  - OBJECTIVE: The aim of this case series study is to evaluate the outline and
      pattern of male and female breast diseases in Saudi Arabia. Also to compare 8
      studies of literature discussing the profile of malignant and benign female
      breast diseases in the Kingdom. We hope that this study will assist us to
      appreciate the prototype breast diseases in our region. METHODS: Our study
      consisted of 1084 consecutive male and female breast lesions. Data on these
      specimens, received in the time frame of 15 years between January 1984 and March
      2000, was retrieved from the records of the laboratory. The outline of breast
      lesions were tabulated and classified into inflammatory, benign and malignant
      lesions. RESULTS: In female breasts, benign lesions comprised 57% of all lesions
      (mean age 28.5), most commonly reported being fibroadenoma 47%, fibrocystic
      disease 22% and fibroadenosis 14%. Malignant lesions comprised 32.5% of all
      lesions (mean age 48.49), most commonly reported being ductal carcinoma 88% and
      lobular carcinoma 4.5%. Inflammatory lesions comprised 11% of all lesions (mean
      age 35.0), most commonly reported lesion being chronic mastitis 31% and
      ductectasia 19%. Male benign lesions comprised 55 cases (87%). Eight cases (13%)
      of malignant lesions, 6 ductal carcinomas and 2 metastatic adenocarcinomas, were
      also identified. CONCLUSION: The rates for female breast lesions varied in
      different studies but benign fibroadenoma constituted the most common breast
      lesion and secondly ductal carcinoma. The mean age for malignant lesion in 7
      different studies came to be 44.05. In the male breast, carcinomas constituted 3%
      of all breast carcinomas. Gynecomastia being the most common male breast lesion
      constituting 54%.

PMID- 11299402
TI  - Surgical treatment of anal fissures under local anesthesia.
AB  - OBJECTIVE: To evaluate lateral sphincterotomy under a mixture of local anesthesia
      versus general anesthesia in the treatment of anal fissures. METHODS: A
      randomized clinical trial of 62 consecutive patients requiring lateral
      sphincterotomy was carried out at Princess Haya Al-Hussein Hospital in Jordan.
      One group underwent lateral sphincterotomy under general anesthesia, while the
      2nd group had topical anesthetic cream (xylocaine 2%) applied followed by local
      anesthesia. RESULTS: There were no differences between the 2 groups in terms of
      operating time, postoperative pain, nausea or vomiting, pain-free interval after
      operation, analgesia requirements or patients satisfaction with the method of
      anesthesia. CONCLUSION: Topical anesthetics and local anesthesia can be used
      effectively for lateral sphincterotomy and provides an alternative to general
      anesthesia.

PMID- 11299403
TI  - Pediatric thoracic trauma.
AB  - OBJECTIVE: A retrospective analysis of the medical records of children up to 12
      years of age inclusive, who sustained thoracic injuries during a 6-year period.
      METHODS: Ninety-one children were treated at King Fahad National Guard Hospital,
      Riyadh from January 1993 through December 1998. The clinical data included age,
      sex, mechanism of injury, associated injuries, pediatric trauma score, treatment
      and mortality. RESULTS: Eighty-seven children (96%) had injuries from blunt
      trauma and 4 from penetrating injuries. Of the blunt trauma cases, 82 children
      sustained motor vehicle accident related injuries, 62 as pedestrians and 20 as
      passengers. Penetrating thoracic injuries occurred in 4 children: 1 stab wound
      and 3 gunshots. The most frequent thoracic injuries were pulmonary contusion
      (70), pneumothorax (32), fractured rib (20) and fractured clavicle (18).
      Extrathoracic injuries included head (45), abdominal (41) and skeletal (26).
      Thoracotomy was required in only 1 child, laparotomy being necessary in 9
      children for intraabdominal injuries. Tube thoracostomy was required in 33
      children. Nine children died from motor vehicle accident related fatal head and
      neck injuries, 8 as pedestrians all with a pediatric trauma score < or = 6.
      CONCLUSION: Thoracic injuries in children below 12 years of age are usually from
      motor vehicle accident related blunt trauma. Pulmonary contusion and pneumothorax
      are the most common thoracic injuries. Most thoracic injuries can be managed
      either conservatively or by tube thoracostomy. Thoracic trauma in children is an
      indicator of multisystem injury with head injury being the most common cause of
      mortality.

PMID- 11299404
TI  - Comparative study of diclofenac sodium and paracetamol for treatment of pain
      after adenotonsillectomy in children.
AB  - OBJECTIVE: To compare the analgesic efficacy of diclofenac sodium and paracetamol
      on post adenotonsillectomy postoperative pain and oral intake. METHODS: Between
      January 1999 and July 2000, 80 children aged 3-14 years, underwent tonsillectomy
      and adenoidectomy for either recurrent tonsillitis or adenotonsillar hypertrophy
      in Prince Zeid Ben Al-Hussein Hospital and Prince Rashid Ben Al-Hussein Hospital.
      Forty-one children received diclofenac sodium suppositories (1-3mg/kg)
      postoperatively, whereas 39 children received only paracetamol syrup (10-15
      mg/kg) in 4 divided doses. All children were observed for postoperative pain,
      oral intake, vomiting, temperature and complications. RESULTS: Children who
      received diclofenac sodium had significantly less pain, less elevation of
      temperature, more oral intake, and started drinking significantly sooner than the
      paracetamol group. Two children in the diclofenac group experienced nausea and
      vomiting compared to 12 children in the paracetamol group in the first day. The
      time to first solid intake was significantly earlier in the diclofenac sodium
      group (p < 0.0001). With regard to complications, one patient in each group
      developed secondary hemorrhage, one child developed otitis media in the 2nd
      group. Each group had one readmission, and 2 children from the paracetamol group
      had an emergency department visit for pain and dehydration. CONCLUSION:
      Diclofenac sodium has a significant effect on decreasing the pain associated with
      swallowing postoperatively and on the general condition of the patient. Improved
      oral intake resulted in a lower incidence of nausea and vomiting and allowed
      safer and earlier hospital discharge.

PMID- 11299405
TI  - Physician's perceptions of fever in children. Facts and myths.
AB  - OBJECTIVE: To ascertain the knowledge and attitude of physicians, regarding fever
      in children. METHODS: A self-administered questionnaire was mailed to 600
      randomly selected pediatricians, family practice physicians, emergency medicine
      physicians and general practitioners, who practice in Saudi Arabia.
      Appropriateness of responses to questions was determined on the basis of current
      medical literature. A rectal temperature of 38.0 degrees C is generally accepted
      as indicative of fever in children. RESULTS: Of the 600 physicians surveyed, 419
      (70%) completed and returned the questionnaire; 17% of the physicians were
      consultants, 28% specialists and 55% general practitioners. Fifty-eight percent
      of the physicians had 10 years or more of experience. A rectal temperature of
      less than 38.0 degrees C was considered to indicate fever by 38% of physicians.
      Nearly 84% of physicians would initiate antipyretic therapy at a temperature of
      38.5 degrees C or less and 56% cited a temperature of 40.0 degrees C or less to
      be dangerous. Only 5% believed that fever was not dangerous, while the remaining
      cited the principal danger of fever to be convulsions (69%), brain damage (35%),
      or death (8%). The responses to the main purpose of antipyretic treatment were to
      prevent convulsions (70%), to make the child comfortable (55%) and to prevent
      brain damage (29%). Approximately 53% of physicians reported that the most
      serious consequences of febrile convulsions were brain damage, learning
      disability, epilepsy, or death. Only 26% of physicians agreed that a sleeping
      child with fever should be left undisturbed. Approximately 25% advised
      inappropriate dosage or administration intervals of paracetamol. Almost all
      physicians recommended sponging or bathing to reduce fever. All respondents try
      to educate parents regarding fever and its management. CONCLUSION: A significant
      number of the surveyed physicians have demonstrated a serious lack of knowledge
      of the nature, dangers and management of an extremely common health problem.
      Physicians differ substantially in their knowledge of, and attitude toward fever
      in children, which is perhaps attributed to their different background in medical
      education and clinical training.

PMID- 11299406
TI  - Serogroups and antimicrobial susceptibility of non-typhoidal salmonellas in
      children.
AB  - OBJECTIVE: To update knowledge regarding the pattern of Serogroups and
      antimicrobial susceptibility of Salmonellas causing gastroenteritis in children
      at the King Khalid University Hospital in Riyadh, Saudi Arabia during the period
      of 1st April 1996 to 30th September 1999. METHODS: The case records of 416
      children, from whom Salmonella species were isolated from stool cultures between
      April 1996 and September 1999 were reviewed. The isolates and susceptibility of
      these Salmonella were carried out accordingly to standard microbiological
      methods. RESULTS: During a period of 3 and 1/2 years a total of 412 non-typhoidal
      Salmonellas were isolated from stool cultures of 416 children who presented to
      King Khalid University Hospital complaining of gastroenteritis. The majority of
      these children (70%) belonged to the age group 0-4 years. Eighty seven percent of
      the Salmonella isolates were Serogroup D1, B and C1. The Serogroups and
      antimicrobial susceptibility of these Salmonellas differed from those previously
      reported from this country and other parts of the world. CONCLUSION: Salmonella
      gastroenteritis is an important clinical condition in infants and children in the
      Kingdom of Saudi Arabia. Salmonella Serogroups D1, B and C predominate as
      causative agents of this condition. Most of the salmonella serogroups isolated in
      this study were highly susceptible to commonly used antimicrobial agents but
      ampicillin showed a rising resistance pattern. This may make it unsuitable
      therapy for Salmonella gastroenteritis.

PMID- 11299407
TI  - Epidemiological profile of malaria in a university hospital in the eastern region
      of Saudi Arabia.
AB  - OBJECTIVE: To study the epidemiological, clinical and hematological profile of
      laboratory-diagnosed malaria cases at King Fahd Hospital of the University, Al
      Khobar, Saudi Arabia, during the period from January 1990 to December 1999, and
      to provide suitable recommendations accordingly. METHODS: This was a clinical
      case series study of confirmed cases presenting to King Fahd Hospital of the
      University during the period from January 1990 to December 1999. A specially
      designed form was used for data collection and 602, laboratory-confirmed cases of
      malaria were retrospectively analyzed. RESULTS: There were 602 cases with a mean
      age of 25.8 + 14.3 and a male to female ratio of 2.9:1. Less than half the cases
      were Saudis (42%), most of whom (93%) reported a history of travel to the
      Southwestern part of the Kingdom. The highest frequency of cases was observed in
      the years 1992, 1994 and 1998 and 40% of the cases were diagnosed during the
      months of February, March and September. Plasmodium falciparum was the most
      common species among Saudi (83%), Sudanese (72%) and Yemeni (64%) patients, while
      Plasmodium vivax was predominant among others. Most of these cases (75%) had a
      history of travel to their home countries (endemic areas). The most common
      clinical presentation was fever (97%), while the most common clinical signs were
      splenomegaly (9%) and jaundice (8%). Anemia (60%) and thrombocytopenia (53%) were
      the most common hematological findings. CONCLUSION: Although it appears that the
      Eastern Province is still free of indigenous malaria transmission, this could not
      be confirmed by the data. Imported cases, however represent a continuous threat
      due to the existence of such vectors as Anopheles stephensi, Anopheles
      fluviatilis, Anopheles sergentii and Anopheles superpictus and a large number of
      non-immune persons. It is recommended that malaria be always considered in the
      differential diagnosis of all acute fevers, especially among those with a history
      of travel to an endemic area. Prompt diagnosis and treatment is necessary.
      Chemoprophylaxis, when traveling to endemic areas is mandatory, as well as the
      use of other primary preventive measures to protect against mosquito bites.

PMID- 11299408
TI  - Is hypertension common in hospitalized type 2 diabetic patients?
AB  - OBJECTIVE: To report on the prevalence and implications of hypertension in
      hospitalized type 2 diabetic patients at King Abdulaziz University Hospital.
      METHODS: Relevant data was retrieved from the medical charts of type 2 diabetic
      patients admitted to the medical unit of King Abdulaziz University Hospital in
      the period between January 1998 and September 1999. Patients' age, sex, body mass
      index, presence of hypertension and hyperlipidemia, degree of glycemic control,
      reason for admission, duration of hospital stay and mortality were recorded.
      RESULTS: A total of 427 patients were studied, 46% of whom were hypertensive.
      Hypertensive diabetics tend to be older, more likely to have a higher body mass
      index and hyperlipidemia, to develop cardiovascular complications and renal
      failure, to stay longer in hospital and to have higher mortality compared to
      normotensive diabetics. CONCLUSION: Hypertension is common in diabetics, early
      treatment of which is important to prevent cardiovascular complications, to
      minimize the progression of microvascular complications and to decrease
      mortality.

PMID- 11299409
TI  - Diabetic neuroarthropathy.
AB  - OBJECTIVE: This study was undertaken to assess the incidence of diabetic
      neuroarthropathy and its related morbidity. METHODS: The medical records of 296
      diabetic patients were analyzed retrospectively between June of 1998 and July of
      1999. The patients with long standing, poorly controlled diabetes mellitus and
      associated peripheral neuropathy were evaluated clinically and radiographically
      for the presence of arthropathic changes in the feet. Clinically, neuropathy was
      considered if there was absence of ankle jerk or glove and stocking sensory loss,
      or both. Radiographically, the presence of stress fractures,
      dislocation/subluxation, lytic or arthritic lesions of the bone and joints were
      taken as indicative of the disease. They were treated conservatively by total
      contact casting or surgically in the form of ray excision, amputation and skin
      grafting. They were followed up for an average period of 13 months. Results were
      evaluated clinically and radiographically. RESULTS: The maximum incidence of
      diabetes mellitus was in the age group of 41-80 years. Diabetic neuropathy was
      present in 37 patients (12.5%). Male to female ratio was 23:14 with an average
      age of 70.42 years. The mean duration of diabetes mellitus was 14.2 years.
      Seventeen feet in 11 patients (4%) were found to have diabetic neuroarthropathy.
      The joints involved were tarsometatarsal (76%), metatarsophalangeal (59%),
      subtalar (47%) and interphalangeal joints (41%). Two patients underwent foot
      amputations. Patients treated with total contact casting resulted in satisfactory
      progress. CONCLUSION: Diabetic neuroarthropathy, a less recognized complication
      of diabetes mellitus needs greater attention in Saudi Arabia. High-risk feet
      should be subjected to routine radiographs or preferably a computerized
      tomography examination. The timely detection of this problem can save many
      patients from disastrous complications.

PMID- 11299410
TI  - Endemic goitre in schoolchildren in high and low altitude areas of Asir region,
      Saudi Arabia.
AB  - OBJECTIVE: A deficiency of iodine is characteristic of mountainous regions of the
      world, and the frequency of goitre in such areas has been recognized for
      centuries. The aim of the present study was to estimate the prevalence of goitre
      among schoolchildren in high and low altitude areas of Asir Region. METHODS: The
      study was carried out upon 940 male students randomly selected from 12 schools at
      2 high altitude areas (Tamnia and Al-Soda) 3150 meters above sea level and one
      low altitude area (Marabah) 500 meters above sea level. All students were
      subjected to clinical examination of the thyroid and classification of goitre
      grading was based on the criteria endorsed by the World Health
      Organization/United Nations Children's Fund/International Council for the Control
      of Iodine Deficiency Disorders. RESULTS: An overall prevalence of goitre of 24%
      was estimated in the areas studied (24% in elementary, 24% in intermediate and
      23% in secondary education). This prevalence was significantly higher (p <
      0.0001) in high altitude (27%, 95% confidence interval: 24%-30%) than in low
      altitude areas (13%, 95% confidence interval: 8%-18%). Children of high altitudes
      were 2.5 times more likely to develop goitre as compared to their counterparts in
      low altitudes (odds ratio = 2.5, 95% confidence interval 1.6-3.8). However,
      comparison between the 2 high altitude areas revealed that children of Tamnia
      area were nearly 2 times more likely to develop goitre than their counterparts in
      Al-Soda (odds ratio = 1.9, 95% confidence interval: 1.3-2.6). CONCLUSION: Endemic
      goitre is more prevalent in mountainous, high altitude areas of Asir Region.
      However, the distribution of goitre in these areas is patchy and differs from
      area to area. Well water might have been a contributing factor for the high
      prevalence in Tamnia.

PMID- 11299411
TI  - Reproductive health of male radiographers.
AB  - OBJECTIVE: To compare certain reproductive health problems reported in 2 groups
      of males, one of which was exposed to x-ray radiation (radiographers) and the
      other group that was not exposed to x-ray radiation. The reproductive health
      problems were miscarriage, congenital anomalies, still births and infertility.
      METHODS: Two groups of men were selected (90 in each group). The first group
      consisted of radiographers and the other groups consisted of men not exposed to x
      ray radiation. The 2 groups were matched for age and source. Relative risk,
      attributable risk percentage and level of significance were calculated. RESULTS:
      Incidence rate of reproductive health problems was increasing with the increase
      in duration of exposure to x-ray radiation ranging between 17% (for those exposed
      for 1-5 years) to 91% (for those exposed for more than 15 years). There were
      significant associations between exposure to radiation and miscarriage (relative
      risk = 1.67, attributable risk percentage = 40%), congenital anomalies (relative
      risk = 10, attributable risk percentage = 90%), still birth (relative risk = 7,
      attributable risk percentage = 86%), and infertility (relative risk = 4.5,
      attributable risk = 78%). CONCLUSION: The incidence rates of reproductive health
      problems reported by male radiographers were significantly higher than that
      reported by the non exposed group and higher than the incidence rates reported in
      community-based studies in Jordan. The incidence rates of fetal death
      (miscarriage and stillbirth together) and infertility reported by our
      radiographers were higher than had been reported by the British radiographers. An
      immediate plan of action is needed to protect our radiographers. Further studies
      are needed in this field taking into account all extraneous variables that may
      affect the reproductive health of radiographers.

PMID- 11299412
TI  - Abnormal uterine bleeding. Diagnostic value of hysteroscopy.
AB  - OBJECTIVE: To determine the specificity, sensitivity and predictive value of
      hysteroscopic impression versus histological diagnosis of endometrial curettings
      in evaluating patients with abnormal uterine bleeding. In addition, to determine
      whether office hysteroscopy can eliminate hospital diagnostic dilatation and
      curettage for patients with abnormal uterine bleeding. METHODS: A retrospective
      study of 556 patients who underwent hysteroscopy and dilatation and curettage for
      abnormal uterine bleeding between January 1995 and December 1998 at the Salmaniya
      Medical Complex in Bahrain. A comparison was made between hysteroscopic
      impression and histological examination. RESULTS: Out of 556 patients who were
      included in the study, 53 were diagnosed to have endometrial polyps
      hysteroscopically, however only 13 patients (24.5%) were confirmed to have polyps
      histologically. Hysteroscopy had revealed submucous leiomyoma in 33 women but
      none of these were diagnosed histologically. Hysteroscopy was highly specific for
      diagnosis of both endometrial hyperplasia and endometrial carcinoma (specificity
      was 85% for endometrial hyperplasia and 99.5% for endometrial carcinoma), however
      the sensitivity of hysteroscopy for diagnosing endometrial cancer was 40% and 30%
      for endometrial hyperplasia. CONCLUSION: Hysteroscopy was more sensitive than
      curettage in detecting endometrial polyps and submucous fibroids, but less
      sensitive than curettage in detecting endometrial hyperplasia and endometrial
      carcinoma. Hysteroscopy should be carried out in conjunction with curettage for
      evaluating women with abnormal uterine bleeding. Office hysteroscopy with
      directed biopsies could be carried out, to reduce hospital diagnostic dilatation
      and curettage.

PMID- 11299413
TI  - Effect of modified tumor antigen on experimentally induced sarcomas.
AB  - OBJECTIVE: To explore the possibility of controlling established tumors by active
      immunization through specific and nonspecific methods. METHODS: By subcutaneous
      methylcholanthrene, a fibrosarcoma was produced in adult Swiss male mice. The
      fibrosarcoma was transplanted into the isogenic strain. The cleared tumor cells
      were injected subcutaneous into the hind leg of the 1st sarcoma group. The 2nd
      group received intraperitoneally sensitized spleen cells. One section of the
      irradiated 3rd tumor group received intraperitoneally sensitized spleen cells and
      subsequently a mild dose of modified tumor antigen. The 2nd section of the 3rd
      group was irradiated in between the administration of modified tumor antigen. In
      both the groups, liver of normal and transplanted tumor bearing mice was
      processed and intraperitoneally injected into the isogenic tumor bearing mice.
      Histopathology and tumor size by calipers was assessed. RESULTS: The first group
      showed enhancement of tumor growth in all its 3 fractions injected at different
      intervals. In the 2nd group, the average survival period was prolonged. In the
      first section of the 3rd group a decrease in tumor size and protracted survival
      was noted. In the transplanted tumor bearing mice, complete suppression of tumor
      growth was observed. In the 2nd fraction of the 3rd group, long survival period
      with regression of tumor was observed. In the 4th group, attenuated tumor and one
      mouse was observed to become tumor free after 60 days. CONCLUSION: Active
      immunosuppression by sensitized spleen cells and vaccines from transplanted
      sarcomas enabled regression of tumor size and longevity in tumor bearing mice.
      The modified tumor antigens, processed isogenic liver cells attenuated to zero
      level in tumor size in isogenic transplanted tumor bearing mice. The results show
      vaccines from allogenic and syngeneic sources bear the potential to regress tumor
      and enhance survival period.

PMID- 11299414
TI  - Lucigenin chemiluminesence. A new approach to study the redox activity of Ehrlich
      ascetic tumor cells.
AB  - OBJECTIVE: To study the mechanism and to measure the oxygenation/reduction
      activity of Ehrlich ascetic tumor cells in an isotonic solution by means of
      lucigenin dependent chemiluminescence. METHODS: All the measurements of the
      chemiluminescence redox activity of Ehrlich ascetic tumor cell samples in
      suspension medium, were carried out using a photon counting system especially
      designed to the purpose. The areas under the chemiluminescence kinetic curves
      were measured at different cell physiological conditions and at different agents
      concentrations effect. RESULTS: The rates of lucigenin chemiluminescence redox
      functional activity of Ehrlich ascetic tumor cells were significantly different
      from normal oxygenation/reduction activity at different physiological
      environments of Ehrlich ascetic tumor cells suspension conditions (i.e. cell
      membrane permeability changes, presence and absence of oxidative or reductive
      agents at different concentrations and oxy/hydroxy free radical protective
      agents). CONCLUSION: The results explain more fully the mechanism and the value
      of a lucigenin dependent chemiluminescence probe of the redox functional activity
      of Ehrlich ascetic tumor cells (at different physiological conditions of
      suspension).

PMID- 11299416
TI  - Male variant of cloacal extrophy.

PMID- 11299415
TI  - A calculus within an anal fistula tract in a diabetic patient.
AB  - A non-insulin dependent diabetic patient with a chronic anal fistula underwent
      fistulectomy. At operation a calculus was discovered. The patient had an
      uneventful recovery and healing of the wound in 4 weeks duration. The only case
      reported previously was in a nondiabetic patient and interestingly from this
      department.

PMID- 11299417
TI  - Tufted hair folliculitis.

PMID- 11299418
TI  - An experience of rigid esophagoscopy in 294 cases.

PMID- 11299419
TI  - Changing trends and etiology of bacteremia in a referral hospital in Saudi
      Arabia.

PMID- 11299421
TI  - Brucellosis and thrombocytopenia.

PMID- 11299420
TI  - Temporomandibular joint osteo-arthrosis-histopathological study of the effects of
      intra-articular injection of triamcinolone acetonide.

PMID- 11299422
TI  - Is the number of microembolic signals related to neurologic outcome in coronary
      bypass surgery?
AB  - Coronary artery bypass surgery (CABG) without cardiopulmonary bypass (CPB) may
      potentially reduce the number of microembolic signals (MES) associated with
      aortic manipulation or generated by the pump circuit, resulting in a better
      neurologic outcome after surgery. Our aim was to compare the frequency of MES and
      neurologic complications in CABG with and without CPB. Twenty patients eligible
      to routine CABG without CPB were randomized to surgery with CPB and without CPB
      and continuously monitored by transcranial Doppler. Neurologic examination was
      performed in all patients before and after surgery. The two groups were similar
      with respect to demographics, risk factors, grade of aortic atheromatous disease
      and number of grafts. The frequency of MES in the nonCPB group was considerably
      lower than in CPB patients, however, we did not observe any change in the
      neurologic examination during the early postoperative period. Neurologic
      complications after CABG may be related to the size and composition of MES rather
      than to their absolute numbers. A large prospective multicentric randomized trial
      may help to elucidate this complex issue.

PMID- 11299423
TI  - Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected
      members.
AB  - Depressed natural killer (NK) cell activity has been showed in family members of
      patients with different types of cancer. The present work aimed to evaluate T
      cell subsets and NK cell cytotoxic activity in 15 members of a family with high
      incidence of tumors, such as glioblastoma, gastric, pancreas and colon rectal
      carcinoma, chronic myelocitic leukemia, melanoma and osteoblastoma. As controls,
      19 healthy subjects with the age range equivalent were studied. The enumeration
      of CD3+ lymphocytes and their CD4+ and CD8+ subsets were defined by monoclonal
      antibodies and NK cell cytotoxicity towards K562 target cells were evaluated by
      single cell-assay. The results showed in family members low percentage of total T
      cells (CD3+), and their CD4+ subset and impairment of CD4/CD8 ratio in relation
      to control group. All family members presented percentage of NK-target cell
      conjugate formation below the minimum value observed in control group. Thirteen
      people were examined and followed up during five years, in order to assure that
      there was no undiagnosed or unsuspected disease at the moment of evaluation. One
      of them developed osteoblastoma and other malignant melanoma. Two cancer
      patients, with glioblastoma and chronic myelocytic leukemia were studied during
      illness. All the corresponding values were comparable. The persistence of low
      percentage of conjugate formation may be related to a defect on adhesion
      molecules expression in the surface of NK cells that was probably responsible for
      the low activity of these cells presented by the family group. Thus, the
      inheritance mechanism of low adherence of NK cells should have a prognostic value
      in determining the risk of developing tumors.

PMID- 11299424
TI  - APOE epsilon4 and Alzheimer's disease: positive association in a Colombian
      clinical series and review of the Latin-American studies.
AB  - OBJECTIVE: As the strength of the association between the APOE epsilon4 allele
      and Alzheimer's disease (AD) varies across ethnic groups, we studied if there was
      such an association in Colombian patients. METHOD: We performed apolipoprotein E
      (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly
      late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53)
      diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary
      team. Control subjects (n = 44) had no significant cognitive impairment by
      medical interview and neuro-psychological testing. RESULTS: We found a high
      association (OR= 5.1 95%CI 1.9 -13.6) between APOE epsilon4 and AD, in this
      series with predominantly late-onset cases with familial aggregation in 24 cases
      (28.9%). A significant negative association was found between epsilon2 and AD
      (OR= 0.2 95% CI 0.05-0.75). CONCLUSION: Further population-based surveys in
      Colombia are warranted to precise a possible dose effect of APOE epsilon4.

PMID- 11299425
TI  - Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and
      serum levels in a population of Brazilian patients with relapsing-remitting
      multiple sclerosis.
AB  - Cytokines and adhesion molecules have been implicated in the pathogenesis of
      multiple sclerosis (MS), a chronic inflammatory disease of the central nervous
      system. In this study we analyzed intrathecal (CSF) and serum levels of soluble
      intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients
      with clinically definite MS during acute relapse or stable disease. Comparing to
      control groups of healthy individuals and patients with intervertebral herniated
      disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in
      both serum and CSF samples. Regardless stage of disease there was no significant
      difference in the levels of sICAM-1 during acute relapse (657+/-124.9 ng/ml) or
      remission (627+/-36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum
      and CSF, indicate the existence of a continuous inflammatory process within the
      brain tissue of MS patients despite absence of clinical signs of disease
      activity.

PMID- 11299427
TI  - Hemiparetic cerebral palsy: etiological risk factors and neuroimaging.
AB  - The purpose of this paper, which was conducted on 175 children with hemiparetic
      cerebral palsy (H-CP), was to verify the etiological risk period for this
      disease. Etiological risk factors (ERF) were detected through anamnesis: 23% in
      the prenatal period, 18% in the perinatal period and 59% of the patients the
      period was undefined (ERF in the prenatal and perinatal period was 41% and no ERF
      was 18% of the cases. The computerized tomographic scan (CT) and MRI were
      performed on all the patients, who were then classified according to their
      etiopathogenic data: CT1= normal (18%); CT 2= unilateral ventricular enlargement
      (25%); CT 3= cortical/ subcortical cavities (28%); CT4= hemispheric atrophy and
      other findings (14%); CT 5= malformations (15%). CT 5 was associated with
      physical malformations beyond the central nervous system and with prenatal ERF's,
      while CT 2 was associated with the perinatal ERF's, mainly in premature births.
      Magnetic resonance imaging was performed on 57 patients and demonstrated a good
      degree of concordance with the CT. Etiology remained undefined in only 37% of the
      cases after neuroimaging was related to ERF. A high perinatal RF frequency (59%)
      was observed and emphasized the need for special care during this period.

PMID- 11299426
TI  - Interictal hyposexuality in male patients with epilepsy.
AB  - The purpose of this study was to compare the serum levels of androgens between
      hyposexual and non-hyposexual patients with epilepsy. Adult male patients with
      epilepsy were investigated. Serum levels of testosterone (T) and free-T,
      estradiol, and sex hormone binding globulin (SHBG) were measured and the free
      androgen index (FAI) was calculated. While there were no differences between
      hyposexual and non-hyposexual patients in the serum levels of T, free-T, and
      estradiol, or to the FAI, the serum levels of SHBG were significantly higher in
      hyposexual patients than in non-hyposexual patients. Thus, the effects of
      increased SHBG upon serum levels of testosterone biologically active in patients
      with epilepsy and hyposexuality were not detected by the methods used in this
      study. Four (44%) of nine hyposexual patients who were re-evaluated after two
      years follow-up improved sexual performance. Thus, clinical treatment that
      results in good seizure control may improve sexual performance in some patients
      with epilepsy.

PMID- 11299428
TI  - Epilepsy in children with cerebral palsy.
AB  - OBJECTIVE: To describe the prevalence and characteristics of epilepsy in patients
      with cerebral palsy in a tertiary center. METHODS: a total of 100 consecutive
      patients with cerebral palsy were retrospectively studied. Criteria for inclusion
      were follow-up period for at least 2 years. Types and incidence of epilepsy were
      correlated with the different forms of cerebral palsy. Other factors associated
      with epilepsy such as age of first seizure, neonatal seizures and family history
      of epilepsy were also analysed. RESULTS: follow-up ranged between 24 and 151
      months (mean 57 months). The overall prevalence of epilepsy was 62%. Incidence of
      epilepsy was predominant in patients with hemiplegic and tetraplegic palsies:
      70.6% and 66.1%, respectively. First seizure occurred during the first year of
      life in 74.2% of patients with epilepsy. Generalized and partial were the
      predominant types of epilepsy (61.3% and 27.4%, respectively). Thirty-three
      (53.2%) of 62 patients were seizure free for at least 1 year. Neonatal seizures
      and family history of epilepsy were associated with a higher incidence of
      epilepsy. CONCLUSIONS: epilepsy in cerebral palsy can be predicted if seizures
      occur in the first year of life, in neonatal period and if there is family
      history of epilepsy.

PMID- 11299429
TI  - Sudden unexpected, unexplained death in epilepsy autopsied patients.
AB  - Sudden unexpected, unexplained death in epilepsy (SUDEP) has been reported to be
      responsible for 2 to 17% of all deaths in patients with epilepsy. This study was
      conducted to determine the circumstances of SUDEP and the autopsy findings in
      these patients. Fifty-three individuals whose cause of death was related to
      epilepsy were identified and in 30 cases relatives or friends were interviewed
      about the circumstances of death and other information which allowed to classify
      the patients as SUDEP or not. The death certificates were also reviewed. We found
      20 cases of SUDEP. Most of them were found dead lying on the bed with no evidence
      of seizure event, and most of them had pulmonary and/or cerebral edema as the
      cause of death. The incidence and the risk of SUDEP can only be fully ascertained
      if all sudden deaths had postmortem examination. Consensus in certifying SUDEP
      cases would allow better accuracy in national mortality rate.

PMID- 11299430
TI  - Oral lysine clonixinate in the acute treatment of migraine: a double-blind
      placebo-controlled study.
AB  - Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat
      migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid
      that has proven to be effective in various pain syndromes such as renal colic and
      muscular pain. The aim of this double-blind, placebo-controlled study was to
      evaluate the efficacy of oral LC compared to placebo in the acute treatment of
      migraine. Sixty four patients with the diagnosis of migraine, according to the
      IHS criteria, were studied prospectively. Patients received LC or placebo once
      the headache reached moderate or severe intensity for 6 consecutive attacks. With
      regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4
      hours. The consumption of other rescue medications after 4 hours was
      significantly higher in the placebo group. With regard to the severe attacks,
      there was no difference between the active drug group and the placebo group
      concerning headache intensity and consumption of other rescue medications. We
      conclude that the NSAID lysine clonixinate is effective in treating moderately
      severe migraine attacks. It is not superior than placebo in treating severe
      migraine attacks.

PMID- 11299431
TI  - Quantitative study of the myenteric plexus of the stomach of rats with
      streptozotocin-induced diabetes.
AB  - The purpose of the present study was to investigate the morphological and
      quantitative alterations of the myenteric plexus neurons of the stomach of rats
      with streptozotocin-induced chronic diabetes and compare them to those of non
      diabetic animals. Samples from the body of the stomach were used for whole-mount
      preparations stained with NADH-diaphorase and for histological sections stained
      with hematoxylin-eosin. It was observed that diabetes cause a significant
      decrease on the number of neurons.

PMID- 11299432
TI  - Regional differences in the number and type of myenteric neurons of the ileum of
      rats: a comparison of techniques of the neuronal evidentiation.
AB  - We carried out this study with the purpose of analyzing the density of neurons of
      the myenteric plexus in the mesenteric, intermediate and antimesenteric regions
      of the ileum of rats. Whole-mounts stained with four different techniques were
      employed. Through countings under optic microscope in an area of 8.96 mm2 we
      found the following neuronal means with the techniques of Giemsa, NADH-diaphorase
      histochemistry, NADPH-diaphorase and acetylcholinesterase, respectively:
      mesenteric region 2144.40+/-161.05, 1657.80+/-88.23, 473.80+/-19.62, 905.25+/
      22.40; intermediate region 1790.60+/-128.24, 1265.20+/-141.17, 371.30+/-27.84,
      770.25+/-33.12; antimesenteric region 1647.0+/-76.67, 981.80+/-68.04, 298.50+/
      22.75, 704.50+/-69.38. We conclude that there is a variation of neuronal density
      around the intestinal circumference and this fact independs on the technique used
      to stain the neurons, and that in a single region the neuronal density varies
      with the technique employed. We also call attention for the identification of the
      site were countings were carried out, so that the results of research in this
      area are not compromised.

PMID- 11299433
TI  - [Cranioencephalic relationships between Trolard and Labbe veins: neurosurgical
      applications].
AB  - We accomplished an anatomic study of the anastomotic veins of Trolard and Labbe
      in seven human cephalic segments with the objective to accurate its stretch and
      references to facilitate its preservation during surgical procedure. The
      relationship between the Trolard vein and motor cortex was also studied.

PMID- 11299434
TI  - [The sulci and gyri localization of the brain superolateral surface in computed
      tomography and magnetic resonance imaging].
AB  - The knowledge of the superolateral surface brain anatomy is fundamental to
      localize and to approach the cerebral lesions. A literature review of the signs
      and landmarks for the identification of its sulci and gyri in computed tomography
      and magnetic resonance imaging had been done. The combined use of these several
      signs makes possible the sulci and gyri identification and its cerebral lesions
      localization in almost all cases.

PMID- 11299435
TI  - [Central nervous system tuberculosis in children: 1. Clinical and laboratorial
      presentation].
AB  - Tuberculosis still occupies a remarkable place as a worldwide health problem,
      chiefly in emerging countries, like Brazil. The central nervous system (CNS)
      involvement by Mycobacterium tuberculosis is one of the most feared features of
      disease, because of its high morbidity and mortality. This study aimed to
      describe some epidemiological, clinical and laboratorial aspects of 52 children
      in a tertiary pediatric hospital with CNS tuberculosis. At diagnosis, the
      majority of patients showed low age, compromised nutritional status, previous
      contact with bacillary individuals, delayed or absent immunization, advanced
      neurological signs and compatible abnormalities in cerebrospinal fluid (CSF)
      analysis and in radiological findings. The etiologic agent was identified by
      staining methods or CSF and other fluids culturing in 40% of patients. In most
      cases, despite of suggestive clinical, epidemiological and laboratorial picture
      and feasibility of patients access to health care centres, therapy was started
      late.

PMID- 11299436
TI  - [Central nervous system tuberculosis in children: 2. Treatment and outcome].
AB  - Neurologic damage is usual after central nervous system (CSN) tuberculosis
      recovery. Treatment is long, difficult and prone to complications. Many factors
      are enrolled as prognostic determinants. This study aimed to describe the
      treatment and outcome of 52 children with CNS tuberculosis of a tertiary
      pediatric hospital. All of them received standard triple drug regimen, and 41
      (78.8%) received corticosteroids as adjunctive therapy. Hydrocephalus was common
      (28 of 41 tested), but only 8 (15.4%) patients underwent ventricular shunt
      surgery. Hepatotoxicity to anti tuberculosis drugs occurred in 32 (61.5%) cases,
      but in only 3 (9.4%) drug substitution was necessary. There were 8 (15.4%) deaths
      and 24 (46.1%) cases developed neurologic damage after therapy. Patients who did
      not receive steroids during treatment and those with advanced neurological
      involvement at diagnosis showed a tendency to worse prognosis.

PMID- 11299437
TI  - [Fragile X syndrome confirmed by molecular analysis: a case-control study with
      pre and post-puberal patients].
AB  - The fragile X syndrome (FRAXA) is the most common cause of inherited mental
      retardation. However, it has been frequently underdiagnosed in pediatric
      population. The characterization of the most significant pre and post-puberal
      clinical features observed among patients that are positive for the FMR-1
      mutation, is useful as a screening tool for ordering the DNA test. Therefore, a
      screening program for FRAXA has been conducted in a sample of 104 mentally
      retarded individuals (92 males and 12 females), comprehending familial history
      and physical examination in order to determine the clinical characteristics. The
      molecular test for the disease was performed in all individuals. Seventeen
      patients (14 males) were positive for the FMR-1 mutation. Familial mental
      retardation and poor eye contact were the most common clinical findings with
      statistical significance (p<0.05) in FRAXA pre and post-puberal patients. The
      post-puberal patients presented, as opposed to the control group, large ears,
      broad forehead and macroorchidism.

PMID- 11299438
TI  - [Multiple sclerosis: clinical and laboratorial correlation].
AB  - The clinical and demographic characteristics of 86 Brazilian patients with
      clinically definite multiple sclerosis (MS) were compared to the cerebrospinal
      fluid (CSF) findings. The disease course was relapsing-remitting in 71% and
      chronic progressive in 29% of the cases. The IgG index was increased in 76% in
      the chronic progressive status and 46% and 49% during the bout and remission,
      respectively (p < 0.005). Only 36% of the MS patients using corticosteroids had
      increased IgG index, in comparison to the 64% of the patients without
      immunosupressive treatment. Oligoclonal IgG bands were detected in the CSF of 77%
      and 88% of the MS corticosteroids users and non-users, respectively. The
      quantitative study of intrathecal synthesis of IgG contributes to demonstrate the
      immunological differences between the two forms of MS, the relapsing-remitting
      and the chronic progressive. The treatment with corticosteroids decreases
      quantitatively the intrathecal synthesis of IgG but not the presence of
      oligoclonal bands.

PMID- 11299439
TI  - [Using algometry of pressure measuring the threshold of trigeminal pain
      perception in normal volunteers: a new protocol of studies].
AB  - Algometry of pressure is a technique that measures the physiology of the
      nociceptive system. Acting directly on the responsive peripheral nociceptors to
      pressure stimuli, this technique allows the study on nociceptive integrity in
      normal subjects or having different algic syndromes. Utilizing 29 asymptomatic
      volunteers, the threshold of the painful perception was studied, measuring them
      in a direct way over the emergence of the supra-orbital, infra-orbital and mental
      nerves. The following algometric average were recorded: right mental nerve 46.2
      Kg/cm2 and left 48.6 Kg/cm2; right supra-orbital nerve 47.7 Kg/cm2 and left 45.2
      Kg/cm2; right infra-orbital nerve 53.9 Kg/cm2 and left 55.4 Kg/cm2. After
      reviewing the principles of the algometry utilization, we have validated this
      protocol, showing the average values obtained by measuring the trigeminal system,
      afterwards comparing them with an inervated region by cervical branches (major
      occipital nerve) and the temporal muscle.

PMID- 11299441
TI  - [Rathke's pouch cysts: diagnosis and treatment].
AB  - We studied retrospectively a series of four patients with Rathke pouch cysts and
      pointed out to their clinical presentation and treatment. They all occurred with
      female patients. Predominant symptoms were amenorrhea, headache and visual
      disorders. We present a revision of the literature concerning various series of
      Rathke's pouch cysts. We conclude that surgery is the best therapeutical
      procedure and transsphenoidal approach is the best surgical technique.

PMID- 11299440
TI  - [Use of botulinum toxin in the treatment of laryngeal dystonia (spasmodic
      dysphonia): preliminary study of twelve patients].
AB  - Laryngeal dystonia (spasmodic dysphonia) is a movement disorder characterized by
      involuntary contractions of laryngeal muscles involved with vocalization. The
      introduction of botulinum toxin in the treatment of laryngeal dystonia had a
      major clinical impact due to the striking improvement of symptoms. We report the
      preliminary results of therapeutical use of botulinum toxin in the treatment of
      twelve patients with laryngeal dystonia. After an extensive clinical evaluation,
      the patients underwent a videostroboscopic exam for diagnostic confirmation.
      Botulinum toxin was injected in the cricothyreoid membrane, directed towards the
      thyreoaritenoid muscle, with the aid of eletromyography needles. Most of patients
      who underwent botulinum toxin injection had a significant improvement of their
      symptoms (83%), with effects lasting for four months in average and without
      important side effects.

PMID- 11299442
TI  - Surgical management of Guyon's canal syndrome, an ulnar nerve entrapment at the
      wrist: report of two cases.
AB  - Guyon's canal syndrome, an ulnar nerve entrapment at the wrist, is a well
      recognized entity. The most common causes that involve the ulnar nerve at the
      wrist are compression from a ganglion, occupational traumatic neuritis, a
      musculotendinous arch and disease of the ulnar artery. We describe two cases of
      Guyon's canal syndrome and discuss the anatomy, aetiology, clinical features,
      anatomical classification, diagnostic criteria and treatment. It is emphasized
      that the knowledge of both the surgical technique and anatomy is very important
      for a satisfactory surgical result.

PMID- 11299443
TI  - A rare case of intramedullary lipoma associated with cyst.
AB  - Intramedullary lipomas are benign tumours of the spinal cord corresponding to 1%
      of all primitive intramedullary tumours. We report a rare case of "true"
      intramedullary lipoma associated with cyst. The patient underwent subtotal
      resection and the diagnosis was made by histopathological examination. There was
      postoperative neurological improvement.

PMID- 11299444
TI  - Cerebral aneurysmal dilatation in an infant with perinatally acquired HIV
      infection and HSV encephalitis.
AB  - Although most children with human immunodeficiency virus (HIV) infection have
      neurological dysfunction, in childhood the incidence of symptomatic
      cerebrovascular disease is low. Cerebral aneurysmal arteriopathy in childhood
      AIDS has been reported in the past and considered to have a relatively long
      latency following the primary infection. We report a 1 month-old infant with
      congenitally acquired HIV infection, and herpes encephalitis; she presented a
      sudden cardiorespiratory arrest followed by coma and was found to have a giant
      saccular aneurysm of the left basilar artery. Literature review showed that
      cerebral aneurysmal artheriopathy is an unusual manifestation in newborns and
      infants and this case is possibly the youngest patient reported with aneurysma,
      herpes encephalitis and AIDS. The role of HIV and herpes simplex infections in
      the pathogenesis of this lesion is discussed.

PMID- 11299445
TI  - Inflammatory myopathy on HTLV-I infection: case report.
AB  - We describe a 41 years old woman who 17 years ago presented hypotonia and
      proximal muscular weakness in the upper and lower limbs. On neurological
      examination, the biceps, triceps and Achilles reflexes were absent; the
      brachioradialis reflexes were decreased and the patellar reflexes were normal.
      There was bilateral Babinski sign. The remainder of the neurological examination
      was unremarkable. In the investigation a myopathic pattern was found in the
      electromyography. The nerve-conduction study was normal; a ELISA method for HTLV
      I antibodies was positive in the blood and in the cerebral spinal fluid. The
      muscle biopsy showed inflammatory myopathy, compatible with polymyositis. This
      paper focuses the polymyositis in the beginning of an HTLV-I infection case.

PMID- 11299446
TI  - Worsening of Parkinsonism after the use of veralipride for treatment of
      menopause: case report.
AB  - We describe a female patient with stable Parkinson's disease who has shown a
      marked worsening of her motor functions following therapy of menopause related
      symptoms with veralipride, as well as the improvement of her symptoms back to
      baseline after discontinuation of the drug. We emphasize the anti-dopaminergic
      effect of veralipride.

PMID- 11299447
TI  - Menkes disease: case report of an uncommon presentation with white matter
      lesions.
AB  - Menkes disease is a rare X-linked disorder related to a defect in the copper
      metabolism. According to the current literature, the most frequent neuroimaging
      findings are cortical atrophy, chronic subdural effusion or hygroma, and vascular
      abnormalities. White matter lesions may be present before other features of the
      disease and may evolve into atrophy. We hereby report a case of Menkes disease
      with typical history and progression, and an early phase imaging study with
      important white matter abnormalities, which could have lead to diagnostic
      difficulties.

PMID- 11299449
TI  - [Surgical treatment of the occipital condyle fracture: case report].
AB  - We present a case of fracture of the occipital condyle showing neck pain, lesion
      of IX, X and XII cranial nerves and pyramidal syndrome of the four members. A
      review of the literature about the surgical treatment of the occipital condyle
      fracture is done.

PMID- 11299448
TI  - Classic Pick's disease type with ubiquitin-positive and tau-negative inclusions:
      case report.
AB  - We report on a patient presenting Pick's disease similar to the one reported by
      Pick in 1892, with ubiquitin-positive and tau-negative inclusions. His diagnosis
      was made on the basis of clinical (language disturbance and behavioural
      disorders), neuropsychological (progressive aphasia of the expression type and
      late mutism), neuroimaging with magnetic resonance (bilateral frontal and
      temporal lobes atrophy) and brain single photon emission computed tomography
      (frontal and temporal lobes hypoperfusion) studies. Macroscopic examination
      showed atrophy on the frontal and temporal lobes. The left hippocampus displayed
      a major circumscribed atrophy. The diagnostic confirmation was made by the
      neuropathological findings of the autopsy that showed neuronal loss with gliosis
      of the adjacent white matter and apearance of status spongiosus in the middle
      frontal and especially in the upper temporal lobes. There were also neuronal
      swelling (ballooned cell) and argyrophilic inclusions (Pick's bodies) in the left
      and right hippocampi. Anti-ubiquitin reaction tested positive and anti-tau tested
      negative.

PMID- 11299450
TI  - [Saphenous vein graft bypass from the external carotid artery to the supraclinoid
      internal carotid artery to treat a giant aneurysm of the cavernous internal
      carotid: case report].
AB  - Alternative surgical procedures to treat unclippable aneurysms of the
      intracavernous carotid artery include proximal vessel occlusion and trapping.
      Those techniques, even in patients with rich collateral vessels, are associated
      with risk of hemodynamic compromise and ischemic complications. Therefore, a safe
      treatment requires revascularization to maintain blood flow to the involved
      territories. We report the case of a 47-year-old female, with ischemic signs and
      symptoms and a right third nerve palsy caused by a giant aneurysm, partially
      trombosed, of the intracavernous carotid artery. The patient was submitted to
      trapping after a saphenous vein graft bypass from the external carotid artery to
      the supraclinoid internal carotid artery. The surgical result was good without
      complications.

PMID- 11299451
TI  - [Continuing education in in neurology through the INTERNET].

PMID- 11299470
TI  - [The organization of health care for stroke. The stroke units make the
      difference].
AB  - INTRODUCTION: The advantages of care in stroke units (UI) are known, as are those
      of being in neurology wards as compared with the general medical wards, although
      to date there are no studies which make a comparative evaluation of the stroke
      team (EI) as compared with the UI with regard to benefits in care obtained by the
      patients. PATIENTS AND METHODS: We made a sequential analysis from the stroke
      register comparing three groups of patients attended during the years 1994-1996.
      During 1994 the patients were attended in the neurology ward by the EI. In 1995
      an acute UI was set up. The criteria for inclusion or exclusion, health staff and
      technical resources were similar. We analysed the average stay, complications,
      mortality, hospital costs, functional state and destination on discharge.
      RESULTS: We included 1,491 patients: 435 (1994), 529 (1995) and 527 (1996).
      Comparing UI with EI we observed a reduced average stay (29.5%; p<0.001), fewer
      complications (47.8%; p<0.001), better functional state on discharge (Rankin 1 +/
      2 against 2 +/- 2; p<0.0001), increased transference to rehabilitation units
      (78%; p<0.001) with less long-term hospitalisation (22%; VS) and a reduction in
      costs ( up to 14.2%). There was no difference in mortality. CONCLUSIONS: The UI
      is a better system of attendance than EI for the management of strokes, since it
      reduces the average stay, hospital complications and health costs, as well as
      permitting a better functional state on discharge. Therefore treatment in the UI
      makes the difference in prognosis for these patients and the institutional
      expenses.

PMID- 11299471
TI  - [Variables associated with cognitive deterioration in Parkinson's disease].
AB  - INTRODUCTION: The relation between Parkinson s disease (EP) and dementia is both
      complex and controversial in definition, epidemiology and pathology. Data on the
      prevalence of dementia in EP vary widely owing to the different populations
      studied and differences in the definitions used. However, the large population
      studies (> 200,000 persons), with details of the clinical features of the cases
      reviewed, show a prevalence of nearly 30%. OBJECTIVES: We wished to investigate
      whether certain clinical variables in patients with Parkinson s disease, with or
      without cognitive deterioration might affect the development of neurodegenerative
      conditions in these patients. PATIENTS AND METHODS: The 23 patients with
      Parkinson s disease included in this study were selected on the clinico
      diagnostic criteria of idiopathic Parkinson s disease, namely on the following
      clinical characteristics: resting tremor, bradykinesia, rigidity and postural
      instability; we considered that the patients had cognitive deterioration when
      they obtained scores below 28 points on the cognitive mini-examination, a Spanish
      adaptation of the Mini Mental State Examination, which has a maximum possible
      score of 35 points. RESULTS: The results show significant differences in some of
      the variables studied. CONCLUSION: We wished to show which variables, such as the
      age of onset of symptoms and degree of severity of the extrapyramidal disorder in
      patients with EP, are risk factors for development of neurodegenerative
      conditions in these patients.

PMID- 11299472
TI  - [Electrophysiological study of the anomalous innervation of the hand].
AB  - INTRODUCTION: The innervation of the hand frequently differs from the usual
      description that we can find in text books. The most frequent anomalies consist
      on communications among the median and cubital nerves at level of either forearm
      (Martin-Gruber anastomosis) or to more distal level (Richie-Cannieu anastomosis),
      although they are not the only possibilities. OBJECTIVE: To study from a
      electrophysiological point of view or the variants of the normality in the
      innervation of the hand and to define their functional characteristics. PATIENTS
      AND METHODS: We performed an electromyographic and electroneurographic studies on
      patients that suffered wounded (fundamentally) or other pathologies in the
      forearm. RESULTS: The presence of double innervation in abductor pollicis brevis
      and opponens pollicis muscles has been verified in 2.48% of the patients.
      Although, it has not been possible to determine the prevalence of other
      anomalies, the presence of several types of anastomosis has been observed: Martin
      Gruber types I and III, as well as the incomplete innervation on the part of the
      cubital nerve of the muscles of the tenar muscles (only of the opponens
      pollicis). The correct methodology is fundamental in the electrophysiological
      study, so several pitfalls can take place. It would be desirable to employ
      techniques that minimize the problems of dispersion of the current, by means of
      needles. CONCLUSION: It is very important to keep in mind these variations of the
      normality in the innervation of the hand, specially when pronostic and surgical
      treatment are considered.

PMID- 11299473
TI  - [Cases of symptomatic epilepsy at a regional reference neuropediatric unit].
AB  - OBJECTIVE: The objective of this study was to analyze, from an aetiological
      angle, the cases seen with symptomatic epilepsy by the Seccion de Neuropaediatria
      del Hospital Miguel Servet de Zaragoza. PATIENTS AND METHODS: We studied the
      cases diagnosed as having symptomatic epilepsy between May 1990 and November
      1999. RESULTS: Of a total of 4,466 children assessed during the study period, the
      diagnosis of epilepsy was established in 461 children (10.3% of the total). This
      included idiopathic epilepsy in 110 cases (23.9%), cryptogenic epilepsy in 119
      cases (25.8%) and symptomatic epilepsy in 232 cases (50.3%). The aetiologies of
      the symptomatic epilepsies were: prenatal encephalopathies in 137 cases (59%),
      perinatal encephalopathies in 33 (14.3%), postnatal encephalopathies (due to
      accidents, acquired infections and postnatal cerebrovascular accidents) in 20
      (9%), tumours ( including the post-operative period) in 14 (6%), neurocutaneous
      syndromes in 13 (5.6%), metabolic and degenerative disorders in 13 (5.6%) and one
      case of vascular malformation. CONCLUSIONS: The symptomatic epilepsies make up
      half the epilepsies evaluated by the department of neuropaediatrics. In 59% the
      cause was prenatal. Other causes of symptomatic epilepsy were also represented in
      the series. A detailed study of these should help us to understand and manage
      them better. We consider aetiological aspects to be very important in the study
      of epilepsy, since the aetiology is one of the most important factors in
      prognosis.

PMID- 11299474
TI  - [Diagnosis of peripheral neuropathies: a clinical and neurophysiological study].
AB  - INTRODUCTION: The diagnosis of peripheral neuropathy is based on clinical and
      neurophysiological features. This study aims to establish the diagnostic validity
      of different symptoms and clinical signs, as well as its correlation with
      electroneurography (ENG), to determine its sensitivity (SE), specificity (SP),
      positive (PLR) and negative likelihood ratio (NLR) for every peripheral
      neuropathies type. PATIENTS AND METHODS: A sample of 108 patients with clinical
      suspicion of peripheral neuropathy (pain, paresthesias, loss of strength,
      areflexia) was studied. ENG (nerve conduction velocity and response amplitude
      values in 208 nerves [Median and Posterior Tibial]) was used to confirm the
      diagnosis, classifying the sample in axonal group (A), demyelinating (D) and
      normal (N). It was made descriptive statistics of this sample, studies of SE, SP,
      PLR and NLR of symptoms, and association (contingency tables [Chi square] and
      Odds Ratio) between symptoms and clinical features. RESULTS: The patients with
      paresthesias, loss of strength or pathologic reflexes have larger motor latency
      (p< 0.01). Those with paresthesias, areflexia or pain have fewer sensitive
      conduction velocity (p< 0.05). Symptoms's value for sensory damage's diagnosis is
      (SE= 0.92, SP= 0.48, PLR= 1.78, NLR= 0.14). For motor damage (SE= 0.72, SP= 0.68,
      PLR= 2.25, NLR= 0.41). For axonal damage (SE= 0.83, SP= 0.44, PLR= 1.49, NLR=
      0.37). And for demyelinating damage (SE= 0.92, SP= 0.44, PLR= 1.66, NLR= 0.16).
      CONCLUSIONS: The symptoms's combination is much more sensitive and has fewer NLR
      than each isolated symptom in all neuropathic damage's types. Paresthesias's
      presence is more indicative of sensory damage and loss of strength of motor
      damage. Pain is the only symptom that can aim for axonal damage than
      demyelinating.

PMID- 11299476
TI  - [Differentiation between cerebral abscesses and necrotic or cystic tumours by
      means of diffusion sequences].
AB  - INTRODUCTION: The diagnosis of a cerebral abscess is a real challenge since the
      clinical and radiological findings are often non-specific and undistinguishable
      from those seen with cystic or necrotic tumours. Recently it has been suggested
      that diffusion sequences may be useful in the differential diagnosis of a
      necrotic or cystic mass. PATIENTS AND METHODS: Nine patients with cystic or
      necrotic intracranial masses were studied. The diagnoses were: three pyogenic
      abscesses, three metastases and three high grade gliomas. The diffusion images
      were evaluated visually and by means of maps based on the apparent diffusion
      coefficient (CDA). RESULTS: All lesions showed fine iso-intense or slightly
      hyperintense walls in T1 potentiated sequences, and isointense or slightly
      hypointense walls in T2 potentiated sequences. In all cases the wall took up
      gadolinium intensity, with a well-defined smooth edge (ring uptake). In the
      diffusion sequences the abscesses showed a very strong central signal, as
      compared with the low signal of other lesions. The CDA were significantly lower
      in the abscesses than in the tumours. CONCLUSIONS: Since cerebral abscesses are
      potentially curable, early diagnosis should be made. A cerebral abscess should be
      suspected in all cases of cystic or necrotic masses with hypersignals in
      diffusion sequences and low CDA.

PMID- 11299475
TI  - [Cerebral mapping and attention-deficit hyperactivity syndrome].
AB  - INTRODUCTION: The clinical features of the attention-deficit hyperactivity
      disorder are characterized by attention deficit, an impulsive style of behavior
      and cognition and excessive motor activity. The incidence is estimated to be
      between 3 and 5% of the school population, and it is considered that there are
      one or two children with attention deficit in all children s classes during the
      early years of schooling. OBJECTIVE: Electroencephalogram measurements using
      spectral analysis gives fresh information about the cerebral electrogenesis of
      children with attention-deficit hyperactivity disorder. PATIENTS AND METHODS: In
      this study we diagnosed 21 children as having attention-deficit hyperactivity
      disorder and compared them with a control group of 13 healthy children of the
      same average age, at rest and whilst carrying out various tasks. RESULTS AND
      CONCLUSIONS: Greater values of delta relative amplitude were found in the
      attention-deficit hyperactivity disorder group in their basal EEG at the F7, F8,
      FP1, FP2, F3, F4 and C3 sites. During visual testing differences were observed in
      the alpha band, also in the frontal region (F7, FP1, FP2 and F4) with the
      children of the control group showing the higher values. The level of
      significance used was 0.05. The cortical distribution of the dominant frequencies
      was different also. In addition, we present a method for cerebral mapping by
      means of spline functions developed by Duchon, which allow cerebral bioelectrical
      activity to be mapped in three dimensions.

PMID- 11299477
TI  - [Cerebral SPECT in mitochondrial encephalomyopathy. A case report and a review of
      the literature].
AB  - INTRODUCTION: We report a case of mitochondrial encephalomyopathy with a complex
      clinical picture followed-up in the Neurology Department, and fully investigated
      using different techniques, in whom the definite diagnosis was essentially based
      on finding ragged red fibres on muscle biopsy. CLINICAL CASE: The patient was 60
      years old when the definite diagnosis was made. The illness had started in his
      youth and affected different systems and parts of the body. On laboratory
      investigation the serum lactic acid and lactic acid curve were normal, as were
      those of the cerebrospinal fluid. Further complementary tests were done,
      including imaging techniques (cerebral CAT, MR and SPECT). SPECT was done using
      99Tc-HMPAO. Since it was a single case, we can affirm that the diagnosis of
      mitochondrial encephalomyopathy was made on muscle biopsy, supported by other
      complementary investigations, but without being able to classify the case among
      the various mitochondrial encephalopathies since the clinical features were
      common to several of them. CONCLUSION: More sequential studies are needed with
      different imaging techniques, in the same patient, carefully taking into account
      any slight modification in his clinical state, during the time elapsed between
      two consecutive serial follow-up studies.

PMID- 11299479
TI  - [Diagnostic and therapeutic approaches in oculomotor paralyses].
AB  - OBJECTIVES: We wish to unify current criteria regarding oculomotor paralysis
      (POM). Based on our experience, we have designed a diagnostic-therapeutic
      protocol which permits an early approach, especially since botulinum toxin has
      been used for treatment. DEVELOPMENT: To make things easier to understand, we
      start with the concept of POM, including the physiopathogenic description of
      phenomena secondary to eye movements. Then we consider the aetiological
      topographical incidence and assess the overall causes of POM and the relative
      frequency of the involvement of the different cranial oculomotor nerves. Finally,
      we consider each cranial nerve more fully from two different angles: the
      aetiologic-topographic diagnosis and therapeutic attitudes. CONCLUSIONS: The
      current approach to POM should include a systematic study to classify the
      disorder as isolated, associated with other neurological causes or of some other
      type (metabolic, auto-immune, etc). Satisfactory early treatment should include
      consideration of infilbration with botulinum toxin in all paresis or paralysis
      presenting with contractures. In cases of total paralysis the contractures may
      occur within a week of onset of the condition. In partial paralyses close follow
      up of three parameters   evolution of the degree of ocular deviation, limitation
      of movement and exploration of passive movements   makes it possible to determine
      the best moment to treat the contracture by injection of botulinum toxin: This
      treatment resolves or improves the diplopia, with recovery of oculomotor
      equilibrium, when it is given during the acute phase.

PMID- 11299480
TI  - [Molecular genetics of hereditary neuropathies].
AB  - INTRODUCTION: Significant progress in the understanding of the molecular genetics
      and pathophysiology of inherited neuropathies has been achieved during the last
      years. DEVELOPMENT: The causative genetic defects of most of the demyelinating
      forms are known and different chromosomal loci have been identified for the rarer
      axonal forms. Mutations in genes encoding the myelin proteins peripheral myelin
      protein 22, myelin protein zero and connection 32 are associated with hereditary
      motor and sensory neuropathy type I and II and hereditary neuropathy with
      liability to pressure palsies. Transgenic animals have been generated allowing
      new insights in the pathophysiology of the diseases. CONCLUSION: The
      understanding of the cellular mechanisms leading to hereditary neuropathies will
      contribute to the development of effective therapeutic strategies.

PMID- 11299482
TI  - [Controversies about new drugs for the treatment of dementia. An unfavourable
      view].
AB  - Currently, the important part played by the senile plaque and neurofibrillary
      tangles puts amyloid protein and tau hyperphosphorylation at the centre of a new
      direction in the investigation of the molecular biology and treatment of
      Alzheimer s disease. OBJECTIVE. To consider the scientific evidence regarding the
      limitations of anticholinesterase treatment. DEVELOPMENT. Most of the clinical
      trials with anticholinesterase inhibitor drugs have been too short (3-6 months in
      a disease lasting an average of 8.5 years). There is slight clinical improvement
      with a definite therapeutic ceiling. A small proportion of patients respond, but
      there is no way of knowing who these will be. Improvement occurs during the early
      stages of the illness. This means that when the illness is advanced or does not
      respond initially, treatment should be reconsidered. It is necessary for
      consensus to be reached to obtain uniformity of objectives and methodology in
      clinical trials, which have been heterogeneous until now, incorporating the
      results of epidemiological studies. CONCLUSION. Initial expectations of an
      analogy between the cholinergic deficit of Alzheimer s disease and the
      dopaminergic deficit of Parkinson s disease, with the effects on treatment
      implied by this, has been proved false with the passage of time and clinical,
      therapeutic and scientific experience.

PMID- 11299483
TI  - [Are the new drugs for treatment of Alzheimer's disease useful?].
AB  - In recent years several acetylcholinesterase inhibitor drugs have been developed
      for the treatment of Alzheimer s disease. These are expensive and their
      usefulness is doubtful. OBJECTIVE. We wish to review the evidence available with
      regard to the efficacy and effectiveness of the anticholinesterase drugs
      permitted in Spain. DEVELOPMENT. We review the controlled clinical trials,
      systematic reviews and meta-analysis published on the anticholinesterases
      permitted in Spain (tacrine, donepezil and rivastingmine), and also the
      publications on their effectiveness and efficacy. CONCLUSIONS. The evidence
      available seems to show that these drugs are effective in producing modest but
      real cognitive improvement in persons with mild and moderate Alzheimer s disease
      (Type 1 evidence). Cognitive improvement has also been observed in everyday
      clinical practice. Use of these drugs may be associated with a reduction in the
      costs associated with this disease. These drugs are useful and should be used in
      persons with mild or moderate Alzheimer s disease, without any contra-indication.

PMID- 11299481
TI  - [Controversies about the new anti-epileptic drugs].
AB  - OBJECTIVE: The search for the ideal anti-epileptic drug (FAE) which is a drug to
      control all types of seizures, with no side-effects and a good pharmacokinetic
      profile, has been the incentive to carry out research into the development of the
      new FAE for the past ten years. As a result, a total of six new FAES have reached
      the market in Spain in the recent years: viagbatrin (VGB) lamotrigine (LTG),
      gabapentin (GBP), felbamate (FBM), tiagabine (TGB) and topiramate (TPM).
      DEVELOPMENT: The authors describe the available scientific evidence regarding
      efficacy, safety, tolerance, cost and effect on the quality of life of epileptic
      patients with these drugs. CONCLUSIONS: Inclusion of these new FAE has increased
      the therapeutic arsenal available for the treatment of epilepsy, a heterogeneous
      condition, and in general guaranteed comparable efficacy and better tolerance
      than the classical FAE. Besides, some of these FAE have shown selective actions
      in specific epileptic syndromes. However, the safety profile is still not
      completely clear, the direct cost is considerably higher than that of classical
      FAE and they have had only a modest effect on the long-term prognosis of
      epilepsy. Initial expectations of their use have still not been fulfilled.

PMID- 11299478
TI  - [Chronic myasthenia gravis mimicking muscular dystrophy, in eastern Colombia].
AB  - INTRODUCTION. Myasthenia gravis is an apparently well-defined neuromuscular
      disease with some variants, including one recently described as chronic
      myasthenia gravis. CASE REPORT. We present a 22 year old Columbian woman who
      complained of progressive weakness for the previous four years, affecting her
      pelvic and shoulder girdles but with no clinical involvement of the extra-ocular
      muscles. Repetitive stimulation of the neuro-muscular junction of the abductor
      digiti quinti muscle was negative, but positive for myasthenia gravis in the
      trapezius muscle and the right orbital eye muscles. Her symptoms improved and the
      clinical neurophysiological studies were normal again after treatment with
      pyridostigimine, which confirmed the diagnosis.

PMID- 11299484
TI  - [The enigma of diaschisis].

PMID- 11299485
TI  - [Moyamoya disease and primary intraventricular haemorrhage in an adult patient. A
      case report].

PMID- 11299486
TI  - [Puerperal deep cerebral venous thrombosis].

PMID- 11299489
TI  - [The role of nitric oxide synthase, and of granulocytes, in endotoxin-induced
      early myocardial depression].
AB  - The aim of our study was to investigate the role of endothelial and inducible
      nitric oxide synthase (eNOS and iNOS) and granulocytes during hyperdynamic
      endotoxemia, and to study the cardiovascular effects of the non-selective NOS
      inhibitor N-omega-nitro L-arginine methylester (L-NAME) and the selective iNOS
      inhibitor mercaptoethylguanidine (MEG) in the early myocardial depression.
      METHODS: Endotoxemia was induced in anesthetized dogs. Mean arterial pressure,
      cardiac output and peripheral vascular resistance was monitored, left ventricular
      contractility was calculated. Myocardial eNOS and iNOS activities and
      myeloperoxidase (MPO) activity, as the marker of granulocyte infiltration were
      determined from tissue biopsy samples. RESULTS: Endotoxemia was accompanied by a
      short hyperdynamic circulatory reaction, hypotension and myocardial depression.
      We observed an early increase in eNOS and a late increase in iNOS activity. MPO
      activity increased significantly after 8 hr endotoxemia, suggesting considerable
      granulocyte-extravasation. Non-selective NOS-inhibition prevented hypotension,
      exerted positive inotropic effect, but induced a rise in peripheral vascular
      resistance and a further increase in myocardial MPO activity. MEG treatment
      stabilized myocardial contractility on the control level, increased cardiac
      output and attenuated tissue granulocyte infiltration. CONCLUSIONS: The increased
      activity of eNOS and granulocyte infiltration may be responsible for the early
      cardiac depression during endotoxemia. Non-selective NOS-inhibition has
      beneficial effects, but is also induces side-effects by disturbing
      vasoregulation. Selective iNOS-inhibition has no significant hemodynamic effects
      during early endotoxemia, but restores cardiac efficacy probably through
      attenuating granulocyte-associated myocardial dysfunction.

PMID- 11299487
TI  - [Multiple organ failure in experimental pancreatitis].
AB  - BACKGROUND: Multiple organ failure (MOF) is the most severe complication and the
      most frequent cause of death in acute necrotizing pancreatitis (ANP). OBJECTIVE:
      To evaluate the components and the time course of MOF in an experimental model of
      ANP. METHOD: Induction of ANP in rats by a standardised bile-salt infusion into
      the pancreatic duct and i.v. cerulein hyperstimulation. Six hours after AP
      induction animals were randomised into 4 groups to receive (I) no therapy; (II.)
      4 ml/kg/h Ringer lactate (R.L) i.v.; (III) 8 ml/kg/h RL i.v.; or (IV) 4 ml/kg/h
      RL plus an endothelin receptor antagonist. Animals were observed for 24 hours and
      vital parameters were investigated. RESULTS: After 6 hrs all animals presented
      with severe haemoconcentration (hematokcrit > 57%) and oliguria (< 0.5 ml/6 hrs).
      Until 12 hrs following AP-induction in animals without therapy increased
      hematocrit and oliguria was observed. Animals receiving fluid resuscitation had a
      significant drop in hematocrit and kept their blood gas values compensated.
      Between 12 and 24 hrs urine production significantly increased with fluid
      resuscitation and respiratory parameters stabilised except for animals treated
      with 8 ml/kg/h RL. These animals developed arterial hypoxia and hypercapnia.
      CONCLUSIONS: (1) In the early phase of ANP in our model renal failure developed.
      (2) Massive fluid resuscitation that is necessary to increase urine output may
      lead to respiratory distress. (3) Reduction of intravascular fluid loss by
      endothelin receptor blockade is associated with improved renal and respiratory
      function.

PMID- 11299488
TI  - [Feasibility and accuracy of the combined radioisotope and blue-dye guided
      sentinel lymph node biopsy in breast cancer].
AB  - Sentinel lymph node biopsy is a minimally invasive operation for staging regional
      lymph nodes in breast cancer. This method was introduced in the last decade.
      However there are some remaining questions regarding labelling, surgical
      technique, indications, and the pathological examination of the removed sentinel
      lymph nodes which have to be answered before can be introduced as the routine
      clinical practice. 98 patients with primary breast cancer underwent double guided
      (radioisotope and blue-dye) sentinel lymph node biopsy in our department during a
      surgical feasibility study between December 1997 and February 2000. The operation
      was successful in 92 patients (94%). False negative rate, sensitivity and
      accuracy were 15%, 85% and 95% retrospectively. During the learning curve the
      success rate improved from 83% to 99%, the sensitivity from 79% to 89% and the
      accuracy from 88% to 97% and the false negative rate decreased from 21% to 11%.
      In T1 tumors the false negative rate and accuracy were 6% and 98%, while in T2
      tumors these were 24% and 86%. Application of a larger particle sized colloid
      (200-600 nm), subareolar injection and next day operation technique had no
      effects on the results. Double guided sentinel lymph node biopsy is a sensitive
      surgical staging procedure which accurately predicts the lymph node status in T1
      breast tumors. The technique used by us is easy to reproduce, and learn and is
      beneficial in technical and radiation protection aspects.

PMID- 11299492
TI  - [Treatment of anal fistulas].
AB  - The authors describe the traditional operative technique for correction of anal
      fistulae and analyse the outcome of surgical treatment. During a 5-years period
      between 1994 and 1998, 286 patients underwent surgery for anal fistula in the
      department--more than one--third of this population presented with recurrent
      disease. During the operation, the extrasphincteric segment of the anal fistula
      is excised and the margin of the sinus is marsupialized. Introducing a rubber
      band through the sinus tract eliminates lesions that penetrate the sphincter. As
      the tied band shears through the encircled sphincter muscle, the rate of
      transsection is controlled individually, by adjusting the tightness of the rubber
      band as necessary. The inner opening of the fistula is often difficult to
      identify and consequently, excision may be incomplete. This is a serious pitfall
      that commonly leads to recurrence. According to the authors' experience, flushing
      the fistula tract with hydrogen peroxide is the most effective methods for
      pinpointing the inner meatus. Using this technique, postoperative recurrence was
      detected in 30 patients (10%). Moderate impairment of anal continence had been
      observed in 57 patients (20%); however, this never progressed to permanent
      incontinence.

PMID- 11299491
TI  - [Results of surgical treatment of liver abscess, with special emphasis of
      percutaneous puncture and drainage].
AB  - Authors present 5 cases of liver abscess treated with US or CT guided
      percutaneous puncture and/or drainage performed in cooperation of the 2nd
      Surgical Department and the Radiological Department of the University of
      Debrecen. They analyse the indications and results of this method. They also
      include the results of twelve liver abscesses treated surgically. For one or a
      small number of liver abscesses (Bigger than 5 cm) they prefer percutaneous
      drainage combined with systematic antibiotic treatment if the condition is not
      complicated by other surgical diseases, and if the abscesses are accessible for
      radiological intervention. All patients recovered without recurrence during a one
      year follow-up period. The main advantages of this method are smaller trauma and
      fewer complications.

PMID- 11299490
TI  - [Role of surgery, its results and complications, in the combined treatment of
      primary gastric non-Hodgkin lymphoma].
AB  - During ten years 580 patients have been treated for gastric tumour in our
      department, 510 of them were operated on. Resection could be performed in 296
      cases. 17 resections, 5.7 per cent of all were performed because of primary non
      Hodgkin gastric lymphoma. No gastric lymphoma was found among the non-resected
      patients. The preoperative histological diagnosis was correct only in 8 cases.
      MALT origin could be proved in 5 patients. Synchronous adenocarcinoma and
      lymphoma was diagnosed in 2 patients. Staging was decided according to Lugano
      classification. There were six stage I, four stage II, and seven stage IV
      patients. 8 subtotal and 9 total gastrectomy was performed, 5 were extended and 2
      were combined. R0 resection could be carried out in five stage I, two stage II
      and in one stage IV patient. We lost 2 patients in the postoperative period.
      Patients were treated with adjuvant chemotherapy (VEP, CHOP) except for 2
      patients with low grade MALT lymphoma. The likelihood of one-year survival is 73
      per cent, average two-year survival is 63 per cent. When the tumour is operable
      by total gastrectomy we suggest to perform splenectomy as well, despite of the
      fact that some postoperative complications can be related to it. We think it is
      reasonable to perform palliative resection in cases of locally extended stage IV
      tumours, which affect the patient's quality of life: to cease the pain, passage
      troubles, bleeding and to improve the conditions for adjuvant treatment.

PMID- 11299495
TI  - [Acute gastrointestinal bleeding caused by a rare, benign tumor of the duodenum
      (gangliocytic paraganglioma)].
AB  - Diagnosis and treatment of massive gastrointestinal bleeding is sometimes very
      difficult problem in a surgical unit. Authors present a case of a 40 years old
      female with an atypical source of upper gastrointestinal bleeding. The origin of
      the bleeding was detected only by intraoperative enteroscopy. The source of the
      bleeding was a very rare benign tumour of the duodenum (Gangliocytic
      paraganglioma) which involved the papilla of Vater. During the operation
      resection of the pedunculated tumour was carried out, with choledochal--and
      Wirsungoplastyc, associated with external drainage of these ducts. According to
      the literature in preoperative diagnosis of this rare tumour endoscopy,
      angiography, and EUS are very useful. In case of malignancy, metastases radical
      operation-pancreatoduodenectomy--is indicated.

PMID- 11299493
TI  - [Laparoscopic ileo-cecal resection: case report and review of current issues in
      laparoscopic colorectal surgery].
AB  - A successful case of laparoscopic ileocecal resection is presented. The
      laparoscopic surgical techniques are described. Advantages, disadvantages and
      controversial issues surrounding laparoscopic or laparoscopically assisted
      colorectal surgery are discussed. Reviewing the current literature and the
      authors' collective clinical experience, the conclusion is that laparoscopic or
      laparoscopically assisted procedures are clear indications for benign colorectal
      diseases. The authors believe that these approaches can be employed as palliative
      measures in malignant diseases or as curative procedures in prospective
      randomised trials.

PMID- 11299494
TI  - [Necrosis of the galea as rare complication of infection of a traumatic temporal
      hematoma].
AB  - Authors report a case of infective traumatic temporal haematoma causing septic
      focus. The suppurative inflammation developed two weeks after the trauma causing
      necrosis of an extensive part of the galea on a big area of the crown of head. A
      septic process increased producing necrotic alteration of the affected periosteum
      of the cranial bone and plegmon in the tissue of the neck. Authors report the
      surgical plastic procedures that were used to establish a granulating layer and
      to cover the surface in the area of the removed necrotic part of the galea.
      Authors emphasize the significance of the danger of the inflammatory infiltration
      and report the effect of the Curiosin solution on the wound-healing.

PMID- 11299496
TI  - [To the Editors: Sentinel lymph node biopsy for staging early breast cancer].

PMID- 11299499
TI  - [Reexcision and perioperative brachytherapy in the treatment of local relapse
      after breast conservation: a possible alternative to mastectomy].
AB  - Breast conserving surgery and postoperative radiotherapy became widely accepted
      in the last two decades for the treatment of early invasive breast cancer. In
      spite of adequate surgery and radiotherapy, the rate of ipsilateral breast tumor
      recurrence is approximately 10%. In such cases salvage mastectomy is the standard
      treatment, however wide reexcision of the recurrent tumor is also a reasonable
      option for selected patients. The risk of second local relapse is higher
      following further breast conservation compared to mastectomy. The authors report
      the technique of tumor reexcision combined with intraoperative implantation and
      perioperative high dose rate (HDR) bracytherapy of the tumor bed for the salvage
      of recurrence in a previously irradiated breast. One can perform two operative
      interventions at the same time with this method. Irradiation can be started
      safely within 48 hours after surgery. A review of the literature is also
      performed by the authors to demonstrate the role and indication of perioperative
      brachytherapy in the treatment of breast tumor relapse and other cancer
      recurrences. Reexcision is a practicable alternative to mastectomy for solitary,
      parenchymal breast tumor relapse measured 2 cm or less in diameter. Perioperative
      brachytherapy may decrease the risk of second relapse without increasing
      radiation side effects. Further prospective study is required to define the value
      of the prescribed method in comparison with salvage mastectomy.

PMID- 11299498
TI  - [Inguinal hernia repair with mesh plug technique (initial experiences with a new,
      tension-free surgical method)].
AB  - Majority of inguinal hernia repair are performed in Hungary by traditional
      surgical techniques, reconstruction under tension (Bassini, Kirschner,
      Shouldice). Hernia surgery underwent a revolutionary change from the 80's. Set
      out from the United States, tension-free methodologies (Lichtenstein,
      laparoscopy, mesh plug) have spread worldwide, of which early and late results-
      especially recurrence rate--are significantly better than the formerly used
      techniques. Authors introduce the surgical technique of mesh plug hernioplasty
      and their promising experiences after the first 80 operations.

PMID- 11299497
TI  - [Antibiotic prophylaxis for high risk patients undergoing cholecystectomy].
AB  - An open, randomised clinical trial was performed on 435 high risk patients who
      underwent open cholecystectomy between 1 = January 1993. and 31. December 1995.
      The patients were divided into three groups. Group 1 (AMOX/CLAV, N = 179) was
      treated with 1.2 g i.v. amoxicillin/clavulanic acid, the patients in Group 2
      (COMPARATOR, N = 164) were given other antibiotics commonly used for prophylaxis
      in biliary surgery (cefamandole, cefuroxime, cefotaxim). Group 3 (CONTROL, N =
      92) contained patients without any risk factors for infectious complication. In
      this group we did not use antibiotic prophylaxis. The results were analysed with
      Student t, and x2 methods. The wound infection rate in Group 1 was 2.76% versus
      5.48% in Group 2. The difference was significant if the patients were older than
      65 years or the preoperative hospitalisation was longer than 5 days. The
      concentration of amoxycillin/calavulanic acid was measured in the serum, in the
      wall of the gall bladder, in the bile obtained both from the gall bladder and the
      major bile duct. The observed levels were higher than the therapeutic
      concentration in the serum and in the bile gained from the major bile duct,
      whereas lower in the gall bladder wall, and in the bile gained from the gall
      bladder. Systemic antibiotic prophylaxis is required for open cholecystectomy in
      high risk patients.

PMID- 11299501
TI  - [Unusually large stromal tumor of the rectum causing obstruction].
AB  - A male, 74 years old patient with perineal, sacral pain and with defecation
      disorders attended the outpatient clinic of HIETE. The origine of the complains
      was a retrorectal, fist like, rectum narrowing tumor. The tumor was covered by
      normal mucosa from rectal side. Preoperative examinations--endoscopy, CT, MRI
      transrectal US--detected a tumor with size 7 x 6 x 5 cm, growing from the
      muscular wall of the rectum, with no connection with the surrounding tissues.
      Deep biopsy revealed malignant mesenchymal tumor. After preoperative irradiation
      abdominoperineal rectum amputation was performed. The recovery was uneventful.
      The definitive hystological examination proved a gastrointestinal stromal tumor
      (GIST). This type of tumor rarely occurs in the large intestine or in the rectum,
      that why the publishing can be interesting.

PMID- 11299503
TI  - [Treatment of critical lower limb ischemia--where are we standing at the turn of
      the Millennium?].
AB  - The treatment of chronic critical limb ischaemia (CLI) is a very important and
      constantly developing field of vascular surgery. The high incidence of CLI (50
      100/100,000 inhabitants [10]) means that vascular surgeons at a district general
      hospital/county hospital, providing care for 250-300,000 people, see about 120
      150 cases in a year, 70-75% of them needing elective or acute intervention. We
      have witnessed many important changes over the last 1-2 decades in the management
      of this substantial field of vascular surgery. The in situ technique,
      angioscopically assisted valvulotomy, venous cuffs and A-V fistulae at the distal
      anastomosis of an infrainguinal bypass, the intraluminal and subintimal
      angioplasty-technique in hand, graft-surveillance programmes and the more
      aggressive treatment of graft-infection all provide a potentially better chance
      for limb salvage. Do we follow the trends and seize them?

PMID- 11299506
TI  - How to cope with the media after a mistake.
AB  - When a bad outcome occurs in your ED due to a mistake made by staff, be proactive
      in addressing media inquiries. Don't answer questions about a patient's condition
      or treatment without permission. State your point clearly regardless of what
      reporters are asking. Contact patients after a misdiagnosis occurs.

PMID- 11299500
TI  - [Successful surgical treatment of a multiple ruptured true saphenous vein
      aneurysm after an anterior femoro-tibial bypass].
AB  - Despite the fact, that we have been using the saphena magna as an autolog
      transplantatum for femoro-popliteal bypass since more than 50 years, the true
      aneurysma of the saphena graft is rare. Generally the aneurysma formations are
      detectable years after the primary operation, often in a life or limb threatening
      form. In our publication we report a successfully operated case of ruptured true
      saphena aneurysma. The multiplex aneurysma was operated on after a femoro-tibial
      anterior bypass operation, performed seven years earlier. The patient was
      normotensiv, without any laboratory sign of hyperlipidaemia. For the
      reconstruction we used autolog vein, from the upper limb.

PMID- 11299502
TI  - [To the Editors: Zoltan Szabolcs Memorial Meeting].

PMID- 11299505
TI  - New regs up EMTALA ante: it's your job to help staff at 'remote sites' comply.
AB  - As of Jan. 10, 2001, Emergency Medical Treatment and Active Labor Act regulations
      apply to hospital outpatient facilities. Staff at these locations must provide
      anyone with a potential emergency condition with a medical screening exam and
      stabilization, and, if necessary, must transfer the patient. The ED is
      responsible for helping remote site staff provide good patient care and comply
      with EMTALA. Remote sites cannot delay treatment for an EMTALA-related service by
      collecting copays.

PMID- 11299504
TI  - [Abdominal catastrophes and limb arterial occlusions caused by acute aortic
      dissection. Experiences of a longitudinal population-based study of 28 years].
AB  - The authors pursue longitudinal studies since 1972 on a defined population of
      106,000 relating to several questions of the aortic dissection. Till now, in 90
      patients 93 cases of the aortic dissection were found. In seven patients, the
      aortic dissection was complicated with the clinical and pathological symptoms of
      surgical diseases. The vascular complications of the aortic dissection caused
      obstruction of coecomesenteric arteries with severe ischemic signs in four
      patients, obstruction of iliac arteries in two patients and the left sublavian
      artery in one another. In an additional patient with a chronic recurrent
      pancreatitis, the acute aortic dissection as an acute exacerbation of chronic
      pancreatitis was considered. It makes known in a short report of cases the
      clinicopathological features of vascular complications of the thoracoabdominal
      aortic dissections. Their pathomechanisms as well as the possibilities of their
      diagnosis and treatment are reviewing in detail.

PMID- 11299510
TI  - Ornish approach to treating CAD attracts fresh interest.

PMID- 11299507
TI  - Know ED's role in these 3 scenarios.

PMID- 11299514
TI  - Behavioral intervention shows promise in helping teen diabetics achieve metabolic
      control.
AB  - Help teen diabetics get their disease under control. How? New research suggests
      that a behavioral intervention typically used to deal with psychosocial issues
      can have a measurable impact when applied to teens with diabetes.

PMID- 11299509
TI  - New needlestick law means take steps now.
AB  - To comply with requirements from the Occupational Safety and Health
      Administration and a new federal law, you'll need to take steps to prevent and
      track needlestick injuries: The Needlestick Safety and Prevention Act requires
      you to keep a sharps injury log listing where and how the injury occurred, and
      the type and brand of device used. Review data to spot trends in needlestick
      injuries caused by equipment design flaws and behavior patterns. ED staff must be
      trained annually in needlestick injury prevention, including proper disposal of
      sharps, universal precautions, and what to do if a needlestick occurs. To enforce
      universal precautions, give staff verbal and written warnings and role-model
      appropriate behavior.

PMID- 11299511
TI  - Low-cost intervention produces dramatic results in managing LDL cholesterol.
AB  - Boost cholesterol management efforts with a simple, systematic approach. A simple
      tool backed by a straightforward quality improvement effort can not only help
      providers meet recommended cholesterol targets, but also ease physician burdens
      in the process.

PMID- 11299513
TI  - Seniors with CHF embrace monitoring system based on automatic voice technology.
AB  - Senior CHF patients grow accustomed to automated voice technology. Internet-based
      tools may have a lot to offer, but they don't necessarily get the best results
      when used with a mostly elderly population. However, a telephonic system that
      uses automated voice technology has consistently produced first-rate compliance
      rates while slashing hospitalization in a population of CHF patients. See how the
      system works to boost patient education while enhancing access to "knowledge
      experts".

PMID- 11299515
TI  - Molecular evaluation of the gonadotropin-releasing hormone receptor.
AB  - The gonadotropin-releasing hormone receptor (GnRHR) is a guanine nucleotide
      binding protein-coupled receptor with a characteristic seven transmembrane domain
      motif. It transduces the hypothalamic message carried by the decapeptide
      gonadotropin-releasing hormone. At the gonadotrope cell surface the hormone binds
      to the receptor, leading to pituitary synthesis and secretion of gonadotropins.
      These glycoprotein hormones, in turn, modulate folliculogenesis and ovulation in
      the ovary. Failure of the GnRHR to respond appropriately to its cognate ligand
      has been demonstrated in humans. These patients have genomic mutations in the
      gene for the GnRHR and represent the first individuals with hypogonadotropic
      hypogonadism of autosomal inheritance. The mutant receptors are poorly expressed
      at the cell surface and have a diminished capacity to transduce the hypothalamic
      message efficiently. To date, no mutations have been identified that lead to
      constitutively active receptors and autonomous gonadotropin function. This
      article identifies the mutations in the GnRHR reported to date and reviews how
      these abnormal receptors help us to better understand the biology of this
      interesting molecule.

PMID- 11299508
TI  - Be an 'internal consultant' for your facility.

PMID- 11299512
TI  - Experts urge casting a wider net in cholesterol DM efforts.
AB  - For best results, experts urge providers to broaden cholesterol-lowering efforts.
      Cholesterol management programs that focus exclusively on lowering LDL levels may
      be missing out on the opportunity to prevent adverse events in a significant
      number of people. New research shows that efforts to increase HDL levels and to
      decrease triglycerides may be just as important as focusing on LDL.

PMID- 11299516
TI  - Naturally occurring mutations of the luteinizing hormone receptor gene affecting
      reproduction.
AB  - The luteinizing hormone receptor (LHR) plays a critical role in reproductive
      physiology in both males and females. Naturally occurring mutations in this
      receptor can cause genetically transmitted disorders by producing either gain or
      loss of receptor function. The clinical phenotype of the heterozygous activating
      mutations of the LHR gene has been exclusively described in males, who present
      familial or sporadic pseudoprecocious puberty. Affected boys were usually fertile
      at an adult age. In contrast, homozygous inactivating mutations of the LHR gene
      can cause a distinct spectrum of phenotypes. Severe inactivating mutations of the
      LHR have been recognized as the cause of Leydig cell hypoplasia, a rare form of
      male pseudohermaphroditism, in genetic males and as a novel cause of amenorrhea
      and infertility in genetic females. In addition, inactivating mutations that
      partially inactivate LH signaling can cause micropenis, sometimes accompanied by
      hypospadias and cryptorchidism. Both males and females with homozygous
      inactivating mutations of the LHR gene have suppression of fertility, which can
      represent the chief complaint of these patients.

PMID- 11299517
TI  - Pituitary gene mutations and the growth hormone pathway.
AB  - Hereditary forms of pituitary insufficiency not associated with anatomic defects
      of the central nervous system, hypothalamus, or pituitary are a heterogeneous
      group of disorders that result from interruptions at different points in the
      hypothalamic-pituitary-somatomedin-peripheral tissue axis. These different types
      of pituitary dwarfism can be classified on the level of the defect; mode of
      inheritance; whether the phenotype is isolated growth hormone deficiency (IGHD)
      or combined pituitary hormone deficiency (CPHD); whether the hormone is absent,
      deficient, or abnormal; and, in patients with GH resistance, whether insulin-like
      growth factor 1 (IGF1) is deficient due to GH receptor or IGF1 defects.
      Information on each disorder is summarized. More detailed information can be
      obtained through the electronic database Online Mendelian Inheritance in Man
      which is available at http://www3.ncbi.nlm.nih.gov/Omim/.

PMID- 11299518
TI  - Sexual differentiation.
AB  - Sexual differentiation in humans is genetically and hormonally controlled. In
      response to a signal from a dominant-acting gene on the Y chromosome, primordial
      cells in the embryonic gonad ridge differentiate into Sertoli cells and affect
      newly migrated germ cells to differentiate as spermatogonia, thus creating a
      testis. The cells of the embryonic testis secrete hormones that lead to the
      development of most, if not all, male secondary sexual characteristics. The
      Sertoli cells secrete mullerian inhibitory factor (MIF), causing regression of
      the mullerian ducts and of stray oogonia. The Leydig cells secrete testosterone,
      causing differentiation and growth of the wolffian duct structures.
      Dihydrotestosterone, created by metabolism of testosterone, causes growth of the
      prostate and phallus and fusion of the labioscrotal folds. In the absence of SRY,
      Sertoli cell differentiation does not occur. Rather germ cells migrating into the
      primordial gonad differentiate as oogonia and cause interstitial cells to
      differentiate as granulosa cells. In the absence of MIF and testosterone, the
      mullerian ducts differentiate and grow as female internal genitalia and the
      external genitalia are feminized. Several genes have been identified that control
      testis determination. These include SRY, WT1, SOX9, SF1, XH2, and DAX1. Most of
      these genes were discovered by analysis of rare cases of sex reversal (genetic
      sex of one type, gonadal sex of the other type).

PMID- 11299522
TI  - The Y chromosome and its role in testis differentiation and spermatogenesis.
AB  - The Y chromosome contains genes and gene families that play critical roles in the
      processes of testis determination and testis differentiation. Great strides have
      been made toward defining the genetic pathways associated with the determination
      of gender. The data are summarized and discussed and clinical ramifications are
      considered.

PMID- 11299520
TI  - X chromosome genes and premature ovarian failure.
AB  - Premature ovarian failure (POF) is a disorder characterized by lack of ovulation
      and elevated levels of serum gonadotropins before the age of 40. The etiology of
      POF is not known but different environmental and genetic factors are involved,
      suggesting high heterogeneity of the disorder. The involvement of X-linked genes
      in the etiology of POF was hypothesized on the basis of its frequent association
      with chromosomal rearrangements and monosomies. In recent years a number of genes
      were described. Two genes, FRAXA and POF1B, have been formally demonstrated to be
      responsible for POF. Other genes have been proposed as candidates, but their role
      remains to be demonstrated.

PMID- 11299519
TI  - Mutations in the follicle-stimulating hormone-beta (FSH beta) and FSH receptor
      genes in mice and humans.
AB  - Follicle-stimulating hormone (FSH), a dimeric glycoprotein synthesized in the
      anterior pituitary gland, is important for the production of sex steroids and
      gametes. FSH-beta (FSH beta) and FSH receptor (FSHR) knockout mice display
      impaired ovarian follicular development and infertility in females and small
      testes, oligospermia, and fertility in males. Humans with FSH beta gene mutations
      tend to have a more severe phenotype than those with FSHR gene mutations,
      although infertility and varying degrees of impaired sex steroid production occur
      in both types of mutations. Data from human and mouse mutations in the FSH beta
      and FSHR genes suggest that FSH is necessary for normal pubertal development and
      fertility in males and females.

PMID- 11299521
TI  - Premature ovarian failure and the FMR1 gene.
AB  - FMR1 is an X-linked gene that codes for an RNA binding protein. Expansion of a
      triplet repeat within exon 1 of the gene causes the fragile X syndrome, which is
      characterized by mental retardation and various physical anomalies. The triplet
      repeat in FMR1 can expand to varying degrees. Only the very large expansions in
      which there is concomitant methylation of the gene cause the fragile X syndrome.
      Expansions of between 50 and 200 repeats are premutations. Although premutations
      were originally perceived to be without phenotypic effect, there is now
      substantial evidence that female carriers of premutations are at increased risk
      of having early menopause. The FMR1 premutation is also associated with a
      significant number of cases ascertained because of idiopathic premature ovarian
      failure, particularly when ovarian failure is a familial trait. The molecular
      mechanism to explain the association between ovarian failure and premutations is
      unknown.

PMID- 11299524
TI  - Molecular analysis of implantation.
AB  - The great frontier in reproductive medicine is implantation biology. The
      scientific understanding of normal implantation lags behind what is known in
      areas such as fertilization. For obvious reasons this process is difficult to
      analyze. Recent investigations utilizing molecular biology approaches have
      scratched the surface of the interaction between the developing trophoblast and
      the receptive endometrium. This article describes these approaches with
      techniques such as serial analysis of gene expression (SAGE) and complementary
      DNA array hybridization, which will soon reveal the key mediators of normal
      implantation and result in an understanding of failed implantation.

PMID- 11299526
TI  - Getting started in evidence-based health care: a guide to resources.
AB  - In response to the growing interest in evidence-based health care resources,
      available in print and electronically, a number of new "evidence-based" products
      have been developed to aid the busy clinician. This paper discusses resources
      that will assist the librarian in beginning the educational process about
      evidence-based health care, as well as building a network of informational links
      that will assist clinicians in evidence-based practice.

PMID- 11299527
TI  - What every medical librarian should know about MEDLINEplus.
AB  - Developed in response to a growing need for consumer health information and to
      extend awareness of quality health information resources available on the
      Internet, MEDLINEplus was introduced by the National Library of Medicine (NLM) in
      October 1998. This article gives a brief history and overview of MEDLINEplus and
      describes the content of this full-text consumer health information resource.

PMID- 11299525
TI  - X chromosome defects as an etiology of recurrent spontaneous abortion.
AB  - Recurrent spontaneous abortion is a significant problem in women's health, yet it
      remains a poorly understood phenomenon. Many cases of recurrent spontaneous
      abortion defy diagnosis, and we predict that a subset of these unexplained cases
      are caused by previously unknown, recessively inherited genetic causes. Here, we
      provide background on known genetic factors that contribute to spontaneous
      abortion and describe a novel X chromosome-based genetic mechanism that may be an
      important cause of recurrent spontaneous abortion. Recessively inherited defects
      on the human X chromosome would cause no symptoms in carrier females but would be
      lethal in utero to male conceptions that receive the defective X. Through
      investigation of the basic biology of the X chromosome, we propose that the
      female carriers of such traits can be identified through the molecular finding of
      skewed X chromosome inactivation. Furthermore, we have observed an association
      between skewed X chromosome inactivation and recurrent pregnancy loss, supporting
      the hypothesis that X chromosome defects may be an important, previously unknown
      cause of recurrent pregnancy loss.

PMID- 11299529
TI  - The Community of Science, Inc., Part 2.

PMID- 11299528
TI  - HIV/AIDS-related electronic queries and responses: a three-year analysis.
AB  - Although information about HIV and AIDS has become abundant and accessible,
      questions from health care providers and consumers alike continue to persist. As
      part of an HIV/AIDS outreach program begun in 1995, a Web-based model was created
      to facilitate access to relevant information. The model includes an interactive
      component whereby individuals can pose questions to HIV specialists. Web-based
      queries and responses have been captured and recorded since the project's
      inception. A total of 192 query encounters were collected, sorted, and analyzed
      with descriptive statistics.

PMID- 11299523
TI  - The role of HOX genes in the development and function of the female reproductive
      tract.
AB  - HOX genes are a family of regulatory genes that encode transcription factors and
      are essential during embryonic development. These genes are highly conserved
      between species such that all metazoans possess a common genetic system for
      embryonic patterning. This system is conserved in the reproductive tract, where
      HOX genes are involved in the development of the mullerian system. The
      reproductive tract is unusual in that HOX genes continue to be expressed in the
      adult. HOX genes are essential both for appropriate reproductive tract
      development and for adult function. This article reviews the role of HOX genes in
      the development of the reproductive tract and the effect of HOX gene mutations on
      the development of the reproductive tract in both mice and humans. It then
      reviews the role and regulation of HOX genes in the adult function of the
      reproductive tract, specifically evidence that HOX genes are important for human
      endometrial development and receptivity.

PMID- 11299530
TI  - Herbal resources on the Internet.

PMID- 11299532
TI  - Educational needs assessment: revitalizing a user education program.

PMID- 11299534
TI  - [Effectiveness of radiochemotherapy in esophageal cancers].
AB  - AIM: Simultaneous radio-chemotherapy of the inoperable or irresectable oesophagus
      cancer. METHOD: Thirteen patients with inoperable oesophagus cancer were treated
      between 1995-98. The therapy was started with intraluminal HDR AL irradiation for
      the recanalisation of the oesophagus (Dose 8 Gy in 0.5 cm deep, two-three times,
      one week interval repeated) followed by the percutem megavolt irradiation one
      week after the last HDR AL session (50 Gy total dose, 5 x 2 Gy/week fractions in
      5 week). The chemotherapy was started simultaneously with the percutem megavolt
      irradiation (three courses Cisplatin-5-Fluorouracil combination, repeated in four
      weeks intervals). RESULTS: The swallow function has been improved in 7/13
      patients with 1-3 Units (Deutsche Gesellschaft fur Radio-Onkologie Dysphagical
      Classification) remained unchanged in 4/13 and it got worse in 2/13 patients 1
      and 3 Units, respectively. Side effects: Oesophagitis of different degree
      occurred in all patients, consecutive transitory dysphagia developed in 9/27
      (33.3%) patients. Follow up time: average 14 month (minimum 3 months, maximum 39
      month). The duration of the swallow function improvement: average 13 month
      (minimum 3 month, maximum 39 month). CONCLUSION: The initial results refer to the
      favourable effect of the palliative radio-chemotherapy at the inoperable
      oesophageal cancer.

PMID- 11299531
TI  - MAVEN at the Mayo Clinic.

PMID- 11299533
TI  - [Larynx-preserving pharyngoesophagectomy in the treatment of cancer of the
      pharyngoesophageal junction].
AB  - Pharyngo-laryngo-esophagectomy has been the sole surgical option in the
      management of advanced tumors arising from the pharyngoesophageal junction. This
      operation is associated with high morbidity, mortality and poor quality of life
      due to loss of larynx. The aim of the author was to achieve a reduction in tumor
      size by means of neoadjuvant chemoradiotherapy and so to make the tumor amenable
      to a larynx preserving operation avoiding pharyngo-laryngo-esophagectomy. Between
      1. January 1998 and 31. December 1999, 11 consecutive patients with advanced
      cancer of pharyngo-esophageal junction were treated with neoadjuvant
      chemoradiotherapy (carboplatin, 5-fluorouracil, 30-35 Gy telecobalt irradiation).
      The tumor regressed in all cases and moreover, in 6 patients a larynx preserving
      pharyngo-esophagectomy could be carried out. This operation consists of total
      esophagectomy, resection of posterior pharynx wall and Akiyama-type gastric pull
      up with side-to-side pharyngo-gastrostomy. All 6 patients recovered. In 2 cases
      after neoadjuvant therapy the tumor disappeared from the cervical esophagus and
      so that a pharyngo-laryngectomy and free jejunum transfer could be performed. 3
      other patients remained irresectable due to lymph node metastases. CONCLUSION:
      Larynx preserving pharyngo-esophagectomy is a safe operation by means of which
      the larynx can be preserved even in those patients whose tumor is located at the
      level of pharyngo-esophageal junction, on the posterior wall of the pharynx.

PMID- 11299535
TI  - [Early results of various reconstructions of abdominal incisional hernias with
      Prolene mesh].
AB  - Authors report on the early results of 127 operations performed for incisional
      hernias without selection in the last two years. Prolene mesh (in 8 patients with
      sublay, in 5 with inlay and in 27 with onlay technique) was implanted into the
      abdominal wall. They examined the wound healing influenced by the various methods
      of mesh placement. The time of operation, drainage and postoperative stay was
      shorter, the volume of liquid drained from the wound was less in reconstructions
      of incisional hernias without mesh. In the group without mesh (n = 87) 4 patients
      were lost, and wound complications developed in 8.1%. After mesh implantations (n
      = 40) wound complications occurred in 12.5% of the patients. In 2 patients the
      mesh had to be removed, then a new one reimplanted. There was no difference in
      results of various methods of mesh placements. According to their good
      experiences obtained in operations for incisional hernias, if indicated, the use
      of a mesh in recommended to avoid recurrences.

PMID- 11299536
TI  - [Causes of recurrence after laparoscopic hiatal reconstruction].
AB  - The authors report our recurrent hiatal hernias occurred after laparoscopic
      hiatal reconstruction. The situation found during laparoscopic re-operations are
      illustrated on pictures. The show the methods against the recurrence.

PMID- 11299537
TI  - [Laparoscopic repair of abdominal wall hernias using an intraperitoneal onlay
      prosthetic patch of expanded polytetrafluoroethylene (eptfe)].
AB  - The surgical treatment of ventral abdominal wall hernias is still an unsolved
      problem despite considerable number of conventional methods. Mesh to replace or
      reinforce the defect by anterior approach has marginally reduced the recurrence
      rate, but not the infection rate. The authors describe the technique of
      laparoscopic repair of abdominal wall hernias using an intraperitoneal onlay
      prosthetic patch of expanded polytetrafluoroethylene (ePTFE) in two cases.
      Postoperative complications and the advantages of this technique and other
      published laparoscopic procedures are discussed and compared to the open ventral
      repairs. It is concluded that laparoscopic prosthetic ventral hernioplasty is a
      feasible and safe method. It appears to have less morbidity, especially with
      regard to the infection rate and recurrences, when compared to the open approach.
      However, authors believe that prospective randomized trials will be needed for
      further evaluation.

PMID- 11299538
TI  - [Initial experiences in drainage operation for refractory ascites with saphenous
      valves].
AB  - Authors explains his operational procedure for the treatment of refractory
      ascites to replace generally used shunt types (LeVeen, Denver, Agishi). It means
      leading ascites fluid from the abdominal cavity into the venous system with the
      help of a silicone drain. For maintaining one-way flow they he used the double
      saphenous valve before the sapheno-femoral junction. They gives a step by step
      description of the procedures applied during the operation and also explains the
      first results. The method well deserves attention and further examination because
      it is simple, cheap and reliable due to the use of saphenous valves coming from
      the body itself.

PMID- 11299539
TI  - [Cardiac tamponade caused by intrathoracic pancreatic pseudocyst].
AB  - Authors report on a clinical case of a 41 year old chronic alcoholic male patient
      who was hospitalized due to dominantly chest complaints and mild abdominal
      discomfort. Bilateral pleural and pericardial effusions were detected by
      performed examinations. A large multilocular pancreatic pseudocyst expanded into
      the thoracic cavity was verified in the background of his symptoms. To resolve
      cardiac tamponade developed repeatedly successful operation was performed and the
      patient healed. Authors give a brief summary for the diagnosis and treatment of
      cardiac tamponade with pancreatic origin.

PMID- 11299540
TI  - [Chylothorax as a rare complication of pancreatitis].
AB  - The authors of this study report an extraordinary case which is rather rare even
      in the medical literature. The patient who suffered from recurrence pancreatitis
      was taken to hospital in septic condition. In the background of the septic
      condition lied the acut exacerbate of pancreatitis. Besides, in the right side of
      the thoracic cavity as well as in the peritoneal cavity fistulas of pancreal
      tail's pseudocyst was found. It was proved by clinical, laboratory and imaging
      procedure examinations. During the operation external drainage of the pseudocyst
      was carried out. After several thoracocentesis chylothorax was developed which
      was cured by permanent chest tube drainage.

PMID- 11299542
TI  - [Thoracic surgery and related disciplines in Hungary].

PMID- 11299541
TI  - [Malignant eccrine poroma presenting as a breast tumor].
AB  - Malignant eccrine poroma is a rare malignoma of the skin. Number of the
      publicated cases less than a hundred. Authors detected a case of rapid
      progression malignant eccrine poroma on a young female following a short onset of
      symptoms. According to the case survey of literature is reported.

PMID- 11299543
TI  - [To the Editors: Regarding "Abdominal catastrophes and limb arterial occlusions
      caused by acute aortic dissections"].

PMID- 11299544
TI  - Battling complacency, advancing commitment in 2000.

PMID- 11299545
TI  - Syringe exchange programs: why won't US leaders do the right thing?

PMID- 11299546
TI  - Lipodystrophy remains a troublesome mystery.

PMID- 11299548
TI  - Risk assessment. A five step process.
AB  - Risk assessment is a process which involves identifying hazards in the workplace
      and assessing the risk of them causing harm (Croner's Health Service Risks 1997).
      This step by step approach to risk assessment should make the whole process seem
      less daunting and encourage active participation in this effective method of
      proactive risk management.

PMID- 11299547
TI  - ICAAC eyes PIs, NNRTIs, and STIs.

PMID- 11299549
TI  - The past as prologue to the future.

PMID- 11299550
TI  - Antiseptic skin preparation revisited.
AB  - Preparing the operation site by painting a solution of something onto the skin is
      one of the best preserved rituals in surgery. There appears to be something
      really satisfying about this precursor to the main event, and if the solution
      used is brightly coloured, or stains the skin, then so much the better--you can
      actually see where you've been! I hope than no-one is under the illusion that
      because the whole leg (or arm, or abdomen or anywhere else) is now a sickly shade
      of brown or alarmingly pink, that no pathogenic organisms can possibly have
      survived the onslaught. In this comprehensive review of the literature and
      practice audit, Sally Kent revisits the reasons for skin preparation, and
      recommends the use of well proven research to determine correct practice.

PMID- 11299551
TI  - The view from the other side....
AB  - Continuing our political series, this article brings you the Opposition's views
      on the present day NHS. Remembering that they had 17 years in office in which to
      get it right, this should prove interesting reading. As with the article by Alan
      Milburn in the May issue, this article contains extracts from a keynote speech
      made by Liam Fox at the Conservative party conference last October. There have
      been some changes since then of course, with Frank Dobson no longer the Secretary
      of State for Health, and the budget announcement of extra spending. As with the
      Government, the Conservatives believe that nurses have a vital role to play in
      improving the NHS, so read on and compare these views with the others already
      published. If you're tempted to add your own views, they will be very welcome in
      Open Forum.

PMID- 11299552
TI  - Chaos, cosmology and evolution. The key to understanding practice development in
      perioperative nursing?
AB  - This article looks at the challenges facing practice development today and uses
      key topics in the natural sciences as metaphors to try and stimulate fresh ways
      of thinking about the way forward. The fundamental challenge we face is one of
      borders and boundaries, and this is a theme I will keep returning to in this
      paper.

PMID- 11299556
TI  - Anatomy and physiology: games we play.

PMID- 11299553
TI  - Supportive pharmacology.
AB  - We continue to explore the basics of anaesthesia with another article from
      Rachelle Griffiths, this month looking at supportive pharmacology. If you think
      this looks too complicated for a Back to Basics piece, read it in small chunks-
      and be grateful that you are not my spelling checker, which has gone berserk!
      This Back to Basics series is drawing to a close soon. However, if you have
      suggestions for any more articles, or perhaps an article itself, then do contact
      me via Headquarters.

PMID- 11299554
TI  - Use of pop quizzes as an innovative strategy to promote critical thinking in
      nursing students.

PMID- 11299557
TI  - Fostering sensitivity in clinical conferencing.

PMID- 11299558
TI  - Authoring software for courses delivered on the Web, Part 4:
      Dreamweaver/CourseBuilder.

PMID- 11299555
TI  - Progressive involvement of baccalaureate nursing students in research.

PMID- 11299559
TI  - Need help with your scholarly work? Create a community of passionate scholars.

PMID- 11299560
TI  - Mandating university-based nursing education: Turkey's experience.

PMID- 11299561
TI  - Spotlight on.... Teaching health assessment in advanced practice nursing
      programs.

PMID- 11299562
TI  - Community health assessment using computerized geographic mapping.

PMID- 11299564
TI  - Preparing to retake the NCLEX-RN. The experience of graduates who fail.
AB  - Many schools of nursing counsel and provide practice sessions to their students
      in initial preparation for the National Council Licensure Examination (NCLEX).
      What then of the graduates who fail and are now outside of the educational and
      often supportive environments of schools of nursing? Graduates cannot be employed
      to practice what they have learned, nor do schools of nursing have the programs
      to assist graduates who have failed. How can these graduates be enabled to
      succeed? The authors discuss the stories of 10 graduates who failed the
      examination and their preparation to retake it. Data from their study reveal
      important ways that nurse educators can help graduate nurses during this
      stressful period in their lives.

PMID- 11299565
TI  - Testing leadership and management concepts. The relevancy factor.
AB  - To assist registered nurses returning for their baccalaureate degrees in learning
      concepts presented in a leadership and management course, a relevant take-home
      final examination was developed. The examination incorporated concepts presented
      in the course within a nursing process framework and was to be completed within
      the context of the individual student's place of employment. The development of
      the examination, an evaluation by the faculty and students, and recommendations
      for future use are described.

PMID- 11299563
TI  - Strategies for enhancing student learning by managing ambiguities in clinical
      settings.
AB  - Have you ever watched as care providers, be they student nurses or staff nurses,
      display behaviors that seem to indicate that they are becoming overwhelmed by
      situations in the acute care setting? Have you also observed other providers who
      seem to thrive on the "challenges" presented by these same situations? The same
      situation stimulates responses that reflect opposite ends of a continuum, the
      continuum of tolerance of ambiguity. The nurse educator needs to develop a
      greater understanding of the elements in the clinical situation (the ambiguities)
      that have stimulated the behavioral responses, and how an individual's level of
      tolerance of ambiguity influences reactions to the ambiguous situations. These
      understandings provide the nurse educator with the foundation for developing
      teaching strategies to facilitate effective management of ambiguous situations in
      clinical settings.

PMID- 11299569
TI  - Pressure sores--demographic perspectives.

PMID- 11299566
TI  - Evaluation strategy for essay questions and academic papers.

PMID- 11299570
TI  - The last mystery in physiology?

PMID- 11299568
TI  - Writing for Health Care Publications. A partnership between service and
      education.
AB  - A collaborative partnership between a school of nursing and hospital provided a
      foundation on which to promote writing for publication skills of health care
      professionals from both organizations. The implementation of an interdisciplinary
      graduate course, Writing for Health Care Publications, resulted in publishable
      manuscripts and positive outcomes related to the strategic plans of both service
      and educational settings.

PMID- 11299571
TI  - Sugar for wounds.
AB  - Sugar in its pure form, or incorporated into a paste containing an adhesive
      hydropolymer (gum), is a non-toxic treatment for a variety of wounds. Not only
      does it provide a suitable clean environment for angiogenesis to take place, but
      it will debride the wound surface and reduce odour. The presence of an adhesive
      hydropolymer seems to prevent hypergranulation, scarring and contraction.

PMID- 11299567
TI  - Ethics content in community health nursing textbooks.
AB  - Nurses learn ethics content and ethical decision-making strategies through
      textbooks, basic curricula, continuing education, and professional experience.
      The author describes an ethics content analysis of community health nursing
      textbooks, offers suggestions for the improvement of ethics content for
      textbooks, and raises awareness of the need for more emphasis on public health
      ethics in nursing and public health professional education.

PMID- 11299573
TI  - Examination of the lower limb in high risk patients.
AB  - When 'at risk' patients say that their feet are killing them, they may be right.
      Diabetes mellitus accounts for 50 to 70% of all nontraumatic amputations with a
      three year survival rate of those who undergo a lower limb amputation of 50%.
      Furthermore, when compared to the 'normal' foot, the 'at risk' foot is more
      likely to develop complications, thus it is vital to identify such 'at risk'
      individuals in an attempt to prevent the risk of deformity, ulceration, infection
      and/or necrosis/gangrene. The assessment involves history taking, the examination
      and further investigations, providing the necessary information to make a
      clinical diagnosis and identify 'at risk' groups. During the examination the foot
      wear should be checked, nails and skin condition should be closely inspected and
      tests should be carried out for signs of peripheral neuropathy, ischaemia and
      venous/lymphatic deficiency. Other complications like deformity and increases in
      foot pressure may cause ulceration. Where ulcers are present, an in-depth
      systematic inspection is necessary. A thorough lower limb examination of high
      risk patients provides the necessary information to make a clinical diagnosis and
      plan preventative measures to avoid future complications.

PMID- 11299574
TI  - The effect of a dynamic pressure-redistributing bed support surface upon systemic
      lymph flow and composition.
AB  - INTRODUCTION: It has been postulated that lymphatic insufficiency may have a key
      role in pressure ulcer development. Our hypothesis is that the particular dynamic
      action of the Airwave mattress directly improves lymphatic circulation compared
      to conventional hospital mattresses. METHODS: Seven anesthetized sheep (40-48 kg)
      prepared with chronic prefemoral lymph fistulas and vascular catheters were first
      placed on a standard hospital mattress. Following 30 minutes of equilibration, a
      2 hr control period was started measuring lymph flow and vascular pressures. The
      standard mattress was then exchanged for an active Airwave mattress (Pegasus
      Egerton, Ltd.) and after 30 minutes of equilibration monitored as above. After
      2.5 hr, the support surface was then switched back to the standard mattress and
      monitored as before. Data are mean +/- sem. RESULTS: Initially, on the standard
      mattress, lymph flow was 1.0 +/- 0.2 ml/30 min and increased significantly more
      than 3 fold on the Aireave mattress to 3.7 +/- 0.7 ml/30 min. Upon return to the
      standard mattress, lymph flow decreased to 1.2 +/- 0.2 ml/30 min. Hemodynamic
      variables and arterial blood gases were constant. Lymphatic protein transport
      increased significantly from 1.3 +/- 0.3 micrograms/min to 4.3 +/- 1.0
      micrograms/min when placed on the test mattress and decreased when returned to
      the standard mattress to 1.3 +/- 0.2 micrograms/min. Similar rates of lymph flow
      were seen upon a variant of the Airwave mattress (Cairwave Therapy System).
      CONCLUSIONS: Results support the hypothesis that the Airwave's action increased
      the lymph flow compared to a standard hospital mattress. The dynamic cycle may
      act to aid the pumping action of lymphatics by reducing pressure which would
      otherwise collapse and compress lymphatics leading to local edema and tissue
      swelling.

PMID- 11299575
TI  - Cost-effective strategy for managing pressure ulcers in critical care: a
      prospective, non-randomised, cohort study.
AB  - A prospective, clinical outcome study was undertaken in a critical care
      environment to provide evidence of the effectiveness of a unique pressure
      relieving (PR) alternating mattress system in both the prevention and treatment
      of pressure ulcers in an extremely vulnerable population. In total, 160 critical
      care patients were recruited across five facilities within the United Kingdom.
      Despite the severity of the patients' condition (mean stay 8 days, mortality rate
      24.7%) the incidence of new tissue damage was low (n = 6, 3.75%), predominantly
      superficial and occurring near to death, while 80% (n = 16/20) of pre-existing
      superficial ulcers healed. The study highlights the complexity of assessing
      differing levels of risk in this vulnerable population, where 87.5% of patients
      were ventilated and 93.1% were totally immobile. No correlation was found between
      the occurrence of pressure damage and Waterlow score, serum albumin, hypotension
      and the use of inotropic agents. Cost-effective patient management includes the
      allocation of effective resources to those patients who will benefit most.
      However, if complex risk assessment precludes the accurate assignment of
      resources, an alternative approach may be to provide a minimum, yet effective,
      standard of care to all patients. This strategy also avoids recourse to more
      costly interventions especially where there is little evidence of improved
      patient outcome.

PMID- 11299572
TI  - The cost effectiveness of larval therapy in venous ulcers.
AB  - The treatment of necrotic ulcers involves considerable nursing time and expense.
      The current standard treatment involves repeated application of hydrogels. Larval
      debridement therapy (LDT) has been shown anecdotally to clear ulcers of necrotic
      slough but has never been compared directly with 'modern' therapies. The aim of
      this study has been to compare LDT with hydrogel dressings in the treatment of
      necrotic venous ulcers. 12 patients with sloughy venous ulcers were randomised to
      receive either LDT or the control therapy--a hydrogel. Effective debridement
      occurred with a maximum of one larval application in 6/6 patients. 4/6 patients
      [corrected] in the hydrogel group still required dressings at one month. The
      median cost of treatment of the larval group was 78.64 Pounds compared with
      136.23 Pounds for the control treatment group (p < 0.05). The study confirms both
      the clinical efficacy and cost effectiveness of larval therapy in the debridement
      of sloughy venous ulcers.

PMID- 11299576
TI  - Should weaker study designs ever be preferred over randomised controlled trials.
AB  - Randomised controlled trials are typically cited as the 'best' form of study
      design to be used when comparing the efficacy or effectiveness of different
      devices such as pressure-redistributing beds and mattresses. This article
      presents a RCT that compared two forms of alternating pressure air mattress. No
      statistically significant differences were found between the incidence of sores
      upon the two mattresses. However the study was under-powered, and so was unlikely
      to identify differences in efficacy should they have existed. In discussion it is
      suggested that randomised controlled trials may be less useful to those
      purchasing mattresses than 'weaker' study designs that capture the experience of
      the users of such devices.

PMID- 11299578
TI  - Levels of data: the whys and hows of selection and analysis.
AB  - There are many challenges in selecting the level of a variable for data
      collection and analysis. Meeting these challenges is labor intensive and requires
      considerable skill; however, if a performance improvement project is to produce
      sound results, shortcuts cannot be taken. Studies that purport to show the impact
      of important variables on care influence the allocation of resources. The choice
      of a working unit level of analysis may be highly useful in meeting project goals
      and statistical requirements, but familiarity with multilevel techniques remains
      essential. If all or some of the variables must be aggregated, information about
      individual response rate, the extent and treatment of missing data, and tests of
      the collinearity of the aggregate data need to be made before proceeding with the
      analysis.

PMID- 11299577
TI  - Time: the forgotten outcome.

PMID- 11299580
TI  - Outcomes of a brief inpatient treatment program for mood and anxiety disorders.
AB  - Findings are reported from a study on outcomes of a brief psychiatric inpatient
      treatment program (7-day average) for 67 patients with mood and anxiety
      disorders. Multiple outcomes measures were completed by patients, family members,
      and clinicians at admission, discharge, and 3 months after discharge. Findings
      included significant improvement from admission to discharge, with maintenance of
      gains 3 months later and few readmissions. Implications for psychiatric nursing
      practice in today's health care environment are discussed.

PMID- 11299579
TI  - Cardiovascular outcomes initiative: case studies in performance improvement.
AB  - Multidisciplinary health care teams are trying to change practice in ways that
      will improve patient outcomes. Three case studies are presented that demonstrate
      such practice changes. The practice changes involved a multidisciplinary team
      working toward commonly defined goals over an 18-month period. Several goals were
      attained, and lessons learned are presented. Nursing staff played a significant
      role in identifying and implementing the recommended changes.

PMID- 11299582
TI  - Prevalence of errors in a pediatric hospital medication system: implications for
      error proofing.
AB  - The purpose of this study was to determine the prevalence of errors in the
      medication system of a pediatric teaching hospital. Error was defined broadly to
      capture all deviations in the process from medication order through
      administration of the dose. The long-term goal was to provide direction to
      efforts to error-proof the system. The sample was 3,312 medication orders written
      during 669 patient-days for which a total of 11,978 doses were passed. Errors
      were categorized as intercepted errors (intercepted through the normal processes
      of the medication system) or administration errors (errors that involve the
      patient with or without adverse sequelae). Errors were also categorized as errors
      in primary activities (e.g., prescribing or preparing the medication for
      administration) or supporting activity (e.g., transferring the order to another
      record). A total of 784 errors were identified; 98% were intercepted and 2% were
      administration errors. More errors (71%) occurred in supporting activities than
      in primary activities. Medication systems are complex processes. Errors are
      imbedded in the medication system and are typically intercepted before patients
      are involved. Intercepting errors involves additional work that adds to an
      already cumbersome process. Error proofing will be different for errors in
      primary activities and for supporting activities.

PMID- 11299584
TI  - Comparing two nursing outcomes reporting initiatives.
AB  - Nursing has increasingly found itself in the position of having to show that it
      makes a positive and important impact on health care. Two initiatives have
      surfaced that have potential for indicating the contribution of nursing to health
      care. One of these is the American Nurses Association's Report Card for Acute
      Care. The other is the Nursing Intervention Project's information system model.
      In this article, these initiatives are analyzed in terms of their content and
      potential for providing a framework for the assessment and evaluation of the
      quality of nursing care services. Recommendations for policy changes are made for
      the collection of data to ensure that standards of excellence are met during this
      most challenging era of accountability.

PMID- 11299581
TI  - Survival of nurse-managed centers: the importance of cost analysis.
AB  - Despite the explosive growth in nurse-managed centers (NMC) in the past 20 years,
      most have been unable to achieve financial self-sufficiency, and many have
      closed. Combining costing techniques with outcome measures provides essential
      information needed by NMC for making operating decisions and for marketing NMC
      performance. These outcome data can be persuasive to policy makers and
      institutional decision makers and are crucial for NMC to improve their
      competitiveness in the health care market place.

PMID- 11299583
TI  - Quality pain management outcomes: the power of place.
AB  - This study explores how an organization, as the context of care, influences
      nursing practice and a nursing-sensitive, quality health outcome-pain management.
      The results provide important insights into organizational patterns associated
      with favorable pain management-related outcomes as well as the congruence between
      and among subunits within the organization. Outcomes were most favorable on units
      where nurses had attitudes supportive of aggressive pain management and higher
      levels of coordination and discretion.

PMID- 11299586
TI  - [Popliteal artery entrapment syndrome].
AB  - Popliteal Artery Entrapment Syndrome (PAES) is an uncommon congenital anomaly. It
      arises due to compression of the popliteal artery by tendomuscular structures
      often combined with an anomalous position of the artery. Mostly young men are
      suffering of this disease. There are four common variations of this anomaly. We
      report on a 14 year old patient who had an acute 24 hours duration right leg
      ischemia caused by PAES. Using a posterior approach to the popliteal artery,
      following division of the accessory slip of gastrocnemius muscle we performed an
      arteriotomy and a floating thrombus was removed. The artery was reconstructed by
      direct continuous suture. One year postoperatively the boy has no complaints,
      peripheral pulse is palpable.

PMID- 11299587
TI  - [Primary leiomyosarcoma of vascular origin in the groin causing lower extremity
      venous compression].
AB  - A soft tissue tumor causing left lower extremity swelling in a 43 years old
      female was detected in the left inguinal region and resection was performed at
      the Department of Cardiovascular Surgery of Semmelweis University of Medicine,
      Budapest. Histologic examination revealed primary leiomyosarcoma of vascular
      origin. On the base of this case attention is called to this rare disease, which
      has poor prognosis. Early diagnosis and complete resection plays key role in the
      treatment of leiomyosarcoma and may improve survival.

PMID- 11299591
TI  - [Report from a trip: Laparoscopic surgery for cancer and health care delivery in
      Belgium].

PMID- 11299589
TI  - [As a surgeon for one and a half year in Japan ...].

PMID- 11299585
TI  - [Long-term follow-up results of surgery for chronic pancreatitis].
AB  - Authors evaluate the late results of 51 operated patients by decompression or
      resection procedure for chronic pancreatitis between 1990-94, based on a follow
      up period of 86 months. Only 34% of the 47 investigated patients could be
      classified as "good" results group--it is the half part of the good results of
      their former study based on 20 months follow-up period. The incidence of late
      deaths was very high--27.6%. Eighty-five percent of all the lost patients (11
      pts) died after the seventh postoperative year. The most threatened group seems
      to be the alcoholic and insulin-dependent diabetic patients. This combination was
      the cause of death in third part of the cases. IDDM developed altogether in 9
      patients, on average 3.7 years after the operation, namely it was the consequence
      of the irreversible progressive natural history of disease. The rate of
      disability is 44%, and it is significantly higher in the resected group than
      after decompression, just like the late mortality rat. Based on their results
      authors emphasise that in chronic pancreatitis the short-term (20-36 months)
      follow-up results may be deceptive, real outcome of the surgical treatment could
      be expected only after 5 years postoperatively.

PMID- 11299592
TI  - [To the Editor: Laparoscopic hernia repair].

PMID- 11299588
TI  - [Postoperative insufficiency of duodenal stump sutures caused by Ascaris
      lumbricoides].
AB  - A 43 years old female patient suffered ventricular resection (Billroth II)
      because of tumor. On the 11. postoperative day an Ascaris lumbricoides (with the
      length  of 20 cm) was creeping out of the site of the draining tube onto the
      abdominal wall. Enteral parasites are very rare and strange reasons for
      postoperative duodenal suture insufficience but our case may deserve some
      attention considering the well known spreading of Ascaris infections.

PMID- 11299595
TI  - Digital information evolution: the AIDS Library experience.
AB  - The AIDS Library evolved out of consumer health activism in response to the need
      for the latest HIV information, materials, and technology. In 1998, staff
      implemented a microcomputer-based integrated automated library system with Web
      publishing capability to link catalogs, databases of Philadelphia regional
      services, online publications, and fact sheets. The Web site, <www.ain.org>,
      became "live" December 1, 1998. History leading to its development and future
      plans are presented.

PMID- 11299596
TI  - MD consult: one-stop Web-based clinical information.
AB  - MD Consult is the latest one-stop shop for clinical information. It has assembled
      MEDLINE, full-text journals and textbooks, clinical practice guidelines, patient
      information, and CME courses for the clinician in one location on the Web. This
      service is reviewed from the perspective of the clinician and for use at the
      reference desk. For the clinician, MD Consult is an authoritative, convenient,
      easy-to-use, and inexpensive service. For the librarian, it is important to
      become familiar with its features in order to form an opinion about the product.
      Features and pricing are discussed.

PMID- 11299599
TI  - Prospecting research on the Web: a fund-raiser's primer.

PMID- 11299601
TI  - The evolution of medical student instruction in use of the WWW.

PMID- 11299603
TI  - 'Stepping forward'.

PMID- 11299598
TI  - The Community of Science, Inc.

PMID- 11299600
TI  - Psychiatric resources: a core list for the small psychiatric hospital library.
AB  - There is a dearth of core lists for the mental health librarian and materials
      must be selected from several sources. This list is described as "basic," but it
      does provide a core collection of books, journals and Web sites which can be used
      by mental health librarians to build or evaluate collections. "Classics" not
      contained in this list should also be included in library collections as well as
      a comprehensive handbook, Tasman's Psychiatry, to which mental health
      practitioners can refer for a quick answer to a question. Most importantly, the
      library collection should reflect the purposes and philosophy of the medical
      staff and institution it supports.

PMID- 11299605
TI  - Malignancy mirages.

PMID- 11299597
TI  - Web sites for midwives.
AB  - With increasingly more useful information becoming available on the World Wide
      Web and with the Internet becoming accessible to everyone, an organized and
      annotated review of sites beneficial to midwives is an important tool. In
      addition to being useful to midwifery professionals, this listing will be helpful
      to nursing and midwifery educators and students, to pregnant women and their
      families, and to the reference librarian providing assistance to these
      individuals. This article provides individuals interested in midwifery with the
      ability to choose from evaluated Web sites.

PMID- 11299602
TI  - IAPAC opens regional office in South Africa.

PMID- 11299593
TI  - [Early jejunal feeding in acute pancreatitis: prevention of septic complications
      and multiorgan failure].
AB  - Authors evaluate the effect of early jejunal feeding on septic complications and
      mortality in acute pancreatitis, based on the results of a two-phase,
      prospective, randomized study. In the first part of the study they compared the
      conventional parenteral nutrition with early (started within 24 hours) enteral
      nutrition in a prospective, randomized trial on 89 patients. Forty-eight patients
      were randomized into the parenteral group "A" (Rindex 10, Infusamin S, Intralipid
      10%: 30 kcal/kg) and 41 patients into the enteral group "B" (fed by nasogastric
      jejunal tube Survimed OPD, 30 kcal/kg). The rate of septic complications
      (infected necrosis, abscess, infected pseudocyst) were significantly lower in the
      enteral group (p = 0.08 chi-square test). In the second phase of the study early
      jejunal feeding was combined with imipenem prophylaxis (Tienam, 2 x 500 mg i.v.)
      in the necrotizing cases detected by CT scan. According to the results of 92
      patients the rate of septic complications (p = 0.03), multiple organ failure (p =
      0.14), and mortality (p = 0.13) were further reduced in this group. Authors
      believe that combination of early enteral nutrition and a selective, adequate
      antibiotic therapy may give a chance for prevention of multiple organ failure.

PMID- 11299590
TI  - [Correlation of alcohol consumption and pancreatitis in Hungary].
AB  - Alcoholic etiology of acute pancreatitis is outstanding high in Hungary. The aim
      of this retrospective study was to analyse the etiology of patients of 5 years.
      Between 1990 and 1994 altogether 374 patients were admitted with acute
      pancreatitis, which is three and half times higher than between 1970 and 1974.
      From the 374 cases 220 had alcoholic and only 115 had biliary etiology.
      Altogether in 127 patients developed necrosis, the rate of alcoholic etiology was
      80% in this subgroup. During the last two decades the trend of alcohol
      consumption became one of the most burning question in Hungary. Based on the
      Jellinek's formula alcohologists estimate the number of alcoholics more than one
      million. The number of pancreatitis related death multiplied almost four times
      between 1970 and 1994. The doubling of alcohol consumption was practically
      simultaneous with the increase of morbidity and mortality of pancreatitis.
      Hungary shows the most disfavourable distribution of drink varieties among the
      high-consuming countries in Europe.

PMID- 11299594
TI  - Ovid's evidence-based medicine reviews: a review of a clinical information
      product.
AB  - Evidence-Based Medicine Reviews (EBMR) is a new full-text product from Ovid
      Technologies. EBMR supports the practice of evidence-based medicine (EBM) by
      providing access to two premiere EBM resources: the Cochrane Database of
      Systematic Reviews from the international Cochrane Collaboration, and Best
      Evidence from the American College of Physicians-American Society of Internal
      Medicine. Both resources alert health care professionals, researchers, and
      librarians to clinically relevant and methodologically sound studies by providing
      access to full-text reviews and meta-analyses of clinical literature. Value-added
      features include links to EBMR from MEDLINE, alerting MEDLINE users to available
      reviews. An "EBM Reviews" limit within MEDLINE facilitates access to the EBMR
      database contents.

PMID- 11299604
TI  - Revisiting resistance (this isn't getting any easier).

PMID- 11299607
TI  - The initiation of distance learning at Thomas Jefferson University: the library
      as integral partner.
AB  - In 1998 Thomas Jefferson University offered its first entirely online course.
      Librarians and library staff were integral in the development, support,
      evaluation, and refinement of this course. While staff members may have taken non
      traditional roles in this effort, their roles generally fell within the broad
      guidelines of assisting University faculty with information and knowledge
      management. The development and support of distance course offerings will
      continue to be a focus at Scott Memorial Library.

PMID- 11299609
TI  - Experienced reference librarians--the long view.

PMID- 11299608
TI  - Information needs and information-seeking behaviors of HIV positive men and
      women.
AB  - Although a portion of the HIV/AIDS population has long been active in seeking out
      information in support of self-care, little work has been done to examine closely
      the information needs and information-seeking behaviors of this community
      relative to the provision of medical reference. This exploratory study provides
      insight into the types of information HIV positive individuals seek and the
      resources they consult in gathering information to bolster health and well-being.
      Having a better understanding of the information needs and information-seeking
      behaviors of individuals with HIV/AIDS will facilitate information intervention
      for this community.

PMID- 11299610
TI  - Searching Medscape <http://www.medscape.com>.

PMID- 11299606
TI  - Evidence-based librarianship: searching for the needed EBL evidence.
AB  - This paper discusses the challenges of finding evidence needed to implement
      Evidence-Based Librarianship (EBL). Focusing first on database coverage for three
      health sciences librarianship journals, the article examines the information
      contents of different databases. Strategies are needed to search for relevant
      evidence in the library literature via these databases, and the problems
      associated with searching the grey literature of librarianship. Database
      coverage, plausible search strategies, and the grey literature of library science
      all pose challenges to finding the needed research evidence for practicing EBL.
      Health sciences librarians need to ensure that systems are designed that can
      track and provide access to needed research evidence to support Evidence-Based
      Librarianship (EBL).

PMID- 11299615
TI  - How will the next US president combat the global AIDS crisis?

PMID- 11299612
TI  - Shopping for health information.
AB  - In this time of ongoing health care changes, consumers need to become better
      informed to actively participate in their health care decisions. As a result,
      hospital libraries are being challenged to address this need. Scottsdale
      Healthcare's Health Sciences Libraries have responded to this challenge by
      establishing a Health Information Center at the premiere shopping mall in the
      area. Implementing a Health Information Center at a mall is a unique way to bring
      medical information to the community. The purpose of this paper is to describe
      the planning process, the implementation, and the future vision of the Health
      Information Center at Scottsdale Fashion Square.

PMID- 11299611
TI  - Free MEDLINE and implications for library operations.
AB  - The widespread availability of free MEDLINE systems on the Internet raises issues
      about the continued need to allocate library funds for commercial, fee-for
      service MEDLINE vendors. This paper explores the evolution and acceptance of free
      MEDLINE, looking in particular at NLM's PubMed system. Results of a survey on
      librarian perceptions of PubMed are discussed. The new generation of PubMed
      software is evaluated in the context of end-user needs and educational goals of
      medical libraries.

PMID- 11299614
TI  - Durban: the beginning of one world.

PMID- 11299613
TI  - Food for thought: recipes for the new century.

PMID- 11299616
TI  - 'History will judge us harshly if we fail'.

PMID- 11299617
TI  - AIDS pilgrims ply the vortex (or, the winter's tale).

PMID- 11299618
TI  - [Laparoscopic cardiomyotomy in the treatment of achalasia].
AB  - The laparoscopic cardiomyotomy (Heller) with Dor type anterior fundoplication is
      accepted for treatment of esophageal achalasia. Between December 1994 and
      December 1998, 21 patients with esophageal achalasia underwent laparoscopic
      Heller's operation with Dor's antireflux procedures after preoperative assessment
      which involved radiological, endoscopic and manometric investigations. Results
      were evaluated on the basis of our experiences and postoperative investigations.
      There were no intraoperative complications. Operating time was 40-90' (mean 65').
      Conversion to laparotomy was not required. One patient had postoperative
      stenosis, and another had esophageal perforation which was treated. Postoperative
      manometry in all patients showed a decreased lower esophageal sphincter pressure.
      Based on the obtained results it could be concluded that cardiomyotomy with Dor
      fundoplication through a laparoscopic approach leeds to good functional results
      and seems effective and safe procedure in the treatment of esophageal achalasia.

PMID- 11299619
TI  - [Surgical treatment of duodenal perforation].
AB  - Duodenal ulcer can be cured successfully by the eradication of Helicobacter
      pylori (H. p.) and administration of anti-acid secretory drugs, however, from
      among the complications of duodenal ulcer, perforation with unchanged incidence
      continues to need an urgent operation. The authors examined the case histories,
      results of preoperative examinations, data of operations, and postoperative
      events of 175 patients hospitalized for perforation of duodenal ulcer in the past
      five years. The average age of the 38 women was more than 20 years greater than
      that of the 137 men. The time between the appearance of the serious symptoms and
      the operation exceeds 24 hours in 31 patients. There was serious preoperative
      general condition (ASA IV. and V.) in 13.7% of the cases. In the last year
      infection with H. p. was proved with Pylori Screen II (Orion Diagnostica)
      serological examination in 22 patients. Closure of the perforation was made in
      open fashion in 155 (average operative time: 54.1 min.), laparoscopically in 7
      (average operative time: 117.9 min.) and gastric resection was necessary in 12
      patients (average operative time: 154.6 min.). In 20.4% of the survivors a
      complication was observed. All of the 18 non-survivors (10.3%) were operated on
      in poor condition and beyond recovery. Seven patients operated on
      laparoscopically experienced undisturbed recovery, and stayed in the hospital the
      shortest time (average: 5.4 days). In the authors opinion the preoperative
      knowledge of H. p. infection influences the method of the operation of choice,
      and they recommend the laparoscopic access in elected cases.

PMID- 11299620
TI  - [Changes in the treatment of choledocholithiasis].
AB  - The therapeutic approaches to gallstone disease and bile duct stone changed
      dramatically in the last decade by spreading of endoscopic and laparoscopic
      methods. The authors have reviewed the most frequent curing methods of bile duct
      stone recently. They examined patients treated for gallstone and common bile duct
      stone in Surgical Department and Gastroenterological Department of their
      hospital. Retrospective study was performed to evaluate the issue of treatment
      for gallstone disease in addition to common bile duct stone (CBDS) and papillary
      stenosis in the last six years from 1993 to 1998, in the era of laparoscopic
      cholecystectomy (LC). There was formed a control group from similar patients of
      these two departments, between 1986-1991, in the six-year period before the
      laparoscopic era. The postoperative complications and perioperative mortality
      were analysed in present period compared with the outcome of control group.
      RESULTS: 734 patients were treated by sequential endoscopic laparoscopic approach
      or open operation between 1993-1998: 632 endoscopic sphincterotomy (EST), from
      which 236 LC followed the preoperative EST, 102 open choledochotomy were
      performed. Overall complications were 4.4% and mortality was 0.9% (EST plus LC
      plus open operations.) The control group made up of 534 patients underwent a
      treatment of choledocholithiasis: 196 EST and 338 open choledochotomy were
      achieved. Complications were 10.6% and mortality was 1.9%. The authors
      statistically evaluate the retrospective results. They conclude that there is a
      significant difference in the complications rate between the two groups, but the
      decrease of mortality is not significant. The mean hospital stay is 6.5 days in
      the recent group and this value was 13.4 days in the control group. Saving of
      hospital cost is 62,100 Ft for one patients. The authors think that this
      sequential approach results in a safer and more effective treatment of cholecysto
      choledocholithiasis than the former period's.

PMID- 11299621
TI  - [Initial experiences with sentinel lymph node biopsy in malignant melanoma].
AB  - Elective versus therapeutic lymph node dissection has been a controversial field
      of the surgical treatment of cutaneous malignant melanoma for more than two
      decades. The identification and biopsy of the sentinel lymph node in different
      solid malignancies has become feasible by the method described by Morton in 1992.
      The sentinel lymph node is the first tumor draining lymph node in the regional
      lymph node basin. If metastasis is not proven in the sentinel node by detailed
      histological study those are unlikely in other regional lymph nodes and formal
      lymph node dissection can be omitted. Patients undergoing surgery for primary
      cutaneous (intermediate or high risk) melanoma have been initiated in this
      feasibility study. Of the 40 patients the sentinel lymph node biopsy was
      unsuccessful in two and at least one positive sentinel lymph node was found in
      nine patients. The duration of the procedure is between five and 15 minutes.
      After this feasibility study further prospective and randomized studies are
      projected.

PMID- 11299622
TI  - [A new method of tension-free inguinal hernia repair: "PROLENE hernia system"
      (PHS) (pilot study)].
AB  - Authors report 10 case of tension free inguinal hernia repair with PHS double
      mesh grafts, used for the first time in Hungary. The operative technique is
      described in details. The first results are promising. Patients had minimal
      postoperative pain and recovery time was small. On the base of the results, the
      procedure is suitable for day surgery.

PMID- 11299623
TI  - [Ruptured aneurysm of the common hepatic artery].
AB  - The rupture of aneurysm of the common hepatic artery is a rare disease with high
      mortality. Differential diagnosis and surgical treatment is difficult, which is
      often worsened by the condition of the seriously ill patient and the lack of
      time. The authors report a successfully treated case summarizing the diagnostic
      and therapeutic options and point out the recent changes in etiology.

PMID- 11299624
TI  - [Splenic rupture: a rare complication of colonoscopy].
AB  - Splenic rupture due to colonoscopy is very rare. Only a few cases have been
      reported previously in the English literature. Authors present their own case and
      they call attention to the mechanism of this complication. They conclude
      consequences from the literature.

PMID- 11299625
TI  - [Acute abdominal signs of B-cell non-Hodgkin lymphoma at a young age].
AB  - In this report the authors present the case of a highly malignant non-Hodgkin
      lymphoma in a young operated patient. They call attention to the gastrointestinal
      form which is difficult to diagnose. In this case the lymphoma was detected only
      by laparotomy. The prognosis of secondary generalized lymphoma is poor. In most
      cases just like in the on described above--it ends with sepsis and death.

PMID- 11299626
TI  - [Effect of regional hypothermia on cerebrospinal fluid parameters during
      thoracoabdominal aorta clamping in dogs].
AB  - The most feared complication of thoracoabdominal clamping is the paraplegia or
      paraparesis following ischemic injury of the spinal cord. Early intraoperative
      recognition of this complication has not been solved yet. In our earlier
      experiment we found significant alterations of CSF glucose, lactate, pCO2 and
      Neuron Specific Enolase (NSE) levels during 60 minutes thoracoabdominal aortic
      clamping in dogs. The analysis of these parameters proved to be proper to follow
      metabolism of the spinal cord during this type of surgery. In our present paper
      we studied protective effect of regional hypothermia using peridural cooling by
      registration of above parameters. Statistical analysis of our data showed
      prevention of production of anaerobe metabolites in animals with icy peridural
      irrigation. The biochemical approach is appropriate for monitoring effectiveness
      of regional hypothermia of the spinal cord during aortic surgery.

PMID- 11299627
TI  - [To the Editors: Surgical treatment of hernias].

PMID- 11299628
TI  - Medicare to cover MNT services.

PMID- 11299629
TI  - HACCP and enteral feedings. The blue dye controversy.

PMID- 11299630
TI  - Random unannounced surveys. What you can expect.

PMID- 11299631
TI  - Diabetes in the United States. It is still on the rise, according to the CDC's
      latest report.

PMID- 11299632
TI  - Developing easy-to-read materials.

PMID- 11299633
TI  - Determining price structure.

PMID- 11299634
TI  - Crackdown on a virus.

PMID- 11299635
TI  - Missing memories.

PMID- 11299636
TI  - Deconstructing dyslexia. Blame it on the written word.

PMID- 11299637
TI  - When a coma isn't one.

PMID- 11299638
TI  - Guardian angels.

PMID- 11299639
TI  - The past, present, and future of direct contracting.

PMID- 11299640
TI  - How to sidestep legal landmines in risk contracts.
AB  - While you may have a sound clinical and financial infrastructure in place, do you
      have the legal structure you need to be well-protected when operating under risk
      agreements? An attorney tells how to avoid legal booby-traps that could create a
      disaster.

PMID- 11299641
TI  - Use the Internet to enhance disease management and reduce costs under capitation.
AB  - Risk-based providers have long known that disease management programs reduce
      costs and utilization, and now they are tapping into the Internet to help enhance
      the effectiveness of DM programs by increasing patient contact.

PMID- 11299642
TI  - Health-based risk assessment levels the playing field.
AB  - Although many capitated organizations have used demographic information to assess
      and adjust for health risk, the results have been less than satisfactory. Health
      based risk assessment goes an important step further and shows promise as a
      better predictor of future costs.

PMID- 11299643
TI  - Physician reimbursement rises more from HCFA than plans.
AB  - Data Insight: Data collected from HMOs by Milliman & Robertson indicate that
      physicians aren't seeing much of the premium increases their MCO "partners" have
      been collecting.

PMID- 11299645
TI  - Sources of information on postgraduate medical training programs--2000 update.
AB  - This is the biennial update listing directories, journal articles, Web sites, and
      general books that aid the librarian, house officer, or medical student in
      finding information on medical residency and fellowship programs. The World Wide
      Web has surpassed print resources as the most current and complete location of
      information about postgraduate training programs and specialties.

PMID- 11299644
TI  - Policy makers set sights on regulating risk-bearing groups.
AB  - Can you look to your state government for help if your health plan suffers a
      financial collapse? Don't count on it.

PMID- 11299646
TI  - The use of Ovid local holdings messages: one library's experience.
AB  - The Ovid local holdings feature can be very beneficial to library patrons. This
      article describes the use of the feature for one academic health sciences
      library. Topics covered include how the function works, how it was implemented,
      how it is updated, the impact of electronic journals, and benefits and drawbacks
      of use. Also included are suggested enhancements to the system.

PMID- 11299648
TI  - Library directors--the broad view.

PMID- 11299647
TI  - Health care providers' information seeking: recent research.
AB  - Recent research studies describe typical information-seeking behavior of doctors,
      nurses, and other health care providers. This review identifies and analyzes
      thirty-nine studies and nine reviews published since 1990. The researchers are
      from many disciplines and often work in multi-disciplinary teams. They have used
      both quantitative and qualitative methods to gather self-report and observational
      data. In spite of the increased availability of online bibliographic and full
      text sources in this decade, health care providers are using the same sources
      they used twenty years ago. Self-report studies usually show a higher use of
      published literature than of advice from colleagues; observational studies
      usually show the opposite.

PMID- 11299649
TI  - Resources from the Toxicology and Environmental Health Information Program
      (TEHIP).

PMID- 11299650
TI  - Clinical practice guidelines resources on the Web.

PMID- 11299651
TI  - Hospital library support of Navy medical operational readiness.
AB  - Hospital librarians in Naval Medical Centers and Naval Hospitals provide
      information to support the physicians, nurses, psychologists, chaplains,
      dentists, and corpsmen on ships and on Navy bases worldwide.  The concept of
      "operational readiness" refers to the training required by Navy personnel during
      peacetime to perform war-time missons.  Navy medical librarians receive
      challenging requests.  Providing information electronically through full text,
      electronic main, and fax, is part of the routine when preparing staff to deploy
      to other countries and when supporting them in the field and on ships. 
      Librarians at Naval Medical Center, San Diego help prepare Navy Healthcare
      providers for operations during combat, humanitarian, and peacekeeper missions. 
      This paper describes several Navy medical field operations with brief
      explanations of medical librarians' support.

PMID- 11299652
TI  - Establishing a Medical Informatics Curriculum Committee in the school of
      medicine.

PMID- 11299653
TI  - Health sciences librarianship in the new millennium.
AB  - Is the millennium really a critical point in time or just part of a continuum, in
      which health sciences librarians have always been innovators? Librarians have
      always had special knowledge that enabled them to identify, collect, organize,
      and distribute information. They have always embraced new technology, from the
      printing press to the Internet. As a profession, we must continue to promote how
      our particular skills can reinforce our role in the health care field.

PMID- 11299654
TI  - One small community hospital library's successful outsourcing of document
      delivery: an ongoing study.
AB  - When DOCLINE was implemented in 1985, community hospital librarians were
      beginning to feel the economic pressures of the changing health care arena.
      However, staff and resources were often sufficient or plentiful. Now, fifteen
      years after the creation of DOCLINE, many existing small hospitals either no
      longer have a librarian, an assistant is managing the library, the librarian is
      managing one or more libraries of an integrated system, or the number of
      librarians has been reduced. A system that is heavily staff dependent is no
      longer feasible. In addition, as the role of the community hospital librarian
      evolves into one of instructor and patient education liaison, a system that does
      not permit the librarian to expand such services will be detrimental to the
      entire library program. Following is a discussion of one small community
      hospital's decision to outsource document delivery services as a result of
      staffing changes and the expansion of additional library programs.

PMID- 11299655
TI  - Evolution in the body of HIV nursing knowledge.
AB  - The role nurses occupy in the care of the HIV/AIDS affected has evolved over
      time. This evolution is exhibited in the body of nursing knowledge and is
      recorded in the published literature. The purpose of this study was to describe
      landmarks in the evolution of nursing's involvement in the provision of care to
      HIV/AIDS patients and to examine the body of nursing knowledge relative to
      HIV/AIDS, employing bibliometric analytic techniques. It was expected that the
      literature would grow in both breadth and depth concurrent with nursing's
      increased role in caring for those infected, or at risk for infection, with HIV.

PMID- 11299656
TI  - Where is medical reference Librarianship going in the new millennium?

PMID- 11299657
TI  - A new source of herbal information on the Web: the IBIDS database.

PMID- 11299658
TI  - An introduction to minority health resources on the World Wide Web.
AB  - Health care professionals and consumers often need information about, or targeted
      to, non-White or non-English speaking populations. Minority health resources
      sponsored by a variety of organizations are increasingly being made available on
      the World Wide Web. This information is easily accessible to providers, patients,
      and families, and community service agencies. The heterogeneity of sponsors,
      ranging from federal agencies to consumer advocacy and support groups- and their
      agendas-results in differences of quality, depth of content, and suitability for
      different information seekers. Taking a conservative approach, this article
      presents a collection of starting points whose roots are in established agencies,
      institutions, and organizations already familiar to most health care information
      professionals.

PMID- 11299659
TI  - Challenges for the millennium.
AB  - Health sciences librarians will face many new challenges in the new millennium.
      Some we can predict and some we cannot. The Hospital Information Services columns
      will explore some of these challenges in this and subsequent issues.

PMID- 11299660
TI  - IP/TV PC desktop videoconferencing for nursing preceptoring and evaluation.

PMID- 11299661
TI  - Through the looking glass: finding Internet sites to mirror your collection.
AB  - Many libraries are grappling with the new freedom to link to the Internet
      directly from a Web-based catalog. A conservative approach that locates only Web
      sites replicating a library's print holdings is described. Methods for locating
      URLs include reviewing front matter in reference materials, scouring the Internet
      for material produced both in print and full text on the Web, electronic mailing
      lists, publishers' promotional materials, conferences, and journal articles.
      Readers are encouraged to make links from the catalog to any original material
      produced in Web-readable form by the university, including dissertations and
      conference proceedings.

PMID- 11299662
TI  - [Questions of ethics in nursing: infants nutrition at the intensive neonatal care
      unit--nursing between care and autonomy].
AB  - As comparatively new field of applied ethics, nursing ethics aims at drawing
      attention to ethical issues in nursing and at reflecting these issues. With a
      case study, the potential problems comprised in nursing procedures in the
      nutrition of premature new-borns will be demonstrated. Questions of patient
      autonomy and care, which are relevant also to other instances of nursing, will be
      discussed in relation to this concrete case. The article at hand contributes to a
      definition of what issues nursing ethics addresses.

PMID- 11299663
TI  - [Ethics, applied ethics, professional ethics].
AB  - This study is concerned with "The Familiarity of Basic Rules in Professional
      Ethics Amongst Nursing Staff Members". Here the codification of norms in
      professional ethics is understood to be a necessary step on the way to individual
      nursing ethics. A survey on the study topic showed that there is a lack of
      familiarity in Germany. Therefore the authors conclude that German nursing has
      not yet reached this level of individual ethics. As it became clear in the survey
      that there is a general request for more information, the authors feel bound to
      demand better coverage of the topic in both basic and further training. The
      ethics of nursing, however, are applied ethics. In the following discourse first
      of all the authors will define the term "ethics" and explain the characteristics
      which are of importance in the present day situation. Secondly, they will ask
      what "applied ethics" can be against this background. Finally, the authors will
      discuss what "norms" are as regards professional ethics, how and why they develop
      and of what relevance they may be with respect to the corresponding ethics
      applied.

PMID- 11299664
TI  - [Autonomy, privacy and the implementation of the principle of "informed consent"
      with regard to nursing intervention from the view point of the aged].
AB  - The aim of this study was to describe patient autonomy, privacy and the
      implementation of the principle of informed consent in the care of elderly
      patients in facilities experienced by themselves. This study is part of the
      BIOMED 2 project "Patients' autonomy and privacy in nursing interventions"
      supported by the European Commission. Interview data (n = 95) were collected
      among elderly people in German facilities for geriatrics and in nursing homes.
      The results showed there was a lack of opportunity by the elderly people to make
      self-determined decisions. The principle of "informed consent" was hardly
      realised. The participants felt their privacy was not respected in multi-bedded
      rooms and in situations of dressing and eliminating. One can proceed on the
      assumption that the lack of information, the need of help and the fixed
      organizing structures of the facilities are the reasons why elderly people play a
      rather passive role as patients. It might be possible to improve the autonomy of
      elderly people if the nurses as an advocate supported them to make self
      determined decisions. The implementation of the principle of informed consent
      with regard to nursing interventions would promote both autonomy and respect of
      privacy. Furthermore, one can assume that the autonomy and quality of life of
      elderly people could be promoted if the organizing structures of the facilities
      were more flexible.

PMID- 11299665
TI  - [The quality of nursing care].

PMID- 11299666
TI  - [Quality of nurse-patient relationship: requirements].
AB  - The nursing philosophy of a Swiss hospital describes the nurse-patient
      relationship in terms of mutual respect, support, accompaniment and information.
      With these keywords a literature review has been made. Nine concepts have been
      identified: caring, interpersonal competence, autonomy, confidence, support,
      advocacy, empowerment, reassurance and patient participation. The empirical
      studies and concept descriptions were analyzed for criteria of the nurse-patient
      relationship. In the end 27 quality criteria are stated, which can be used for
      validation of standards assuring quality of care. Using these criteria can be
      seen as a step to an evidence-based practice.

PMID- 11299667
TI  - [Scientific examination of a risk-assessment scale for the evaluation of risk for
      thrombosis].
AB  - Is it possible to measure the risk that a patient develops thrombosis in a valid
      and reliable way? Is the "Messskala zur Festlegung der Thrombosegefahrdung" by
      Peter Kumpel an appropriate instrument to assess such a risk? These questions
      were traced with a convenience sample of 281 patients in the departments of
      Neurosurgery, Neurology and Obstetrics of the University Hospital Freiburg in
      Germany. The "Messskala zur Festlegung der Thrombosegefahrdung" by Peter Kumpel
      was tested for validity, reliability and practicability in a nonexperimental,
      explorative study. The results show a high consensus in the interrater-agreement,
      a rather accidental agreement with the clinical view of the medical doctor and
      the clinical view of the registered nurse and an only statistical measurable
      sensitivity and specificity of the scale. The instrument "directs" the nurses'
      view to a number of risk factors. It supports the pupils and the beginners in
      nursing in a complete assessment and gives the expert nurse a possibility to
      control her assessment of a patient. An organisation has to decide whether and
      why such an instrument should be used.

PMID- 11299668
TI  - [Consultation in pediatric nursing].
AB  - Consultation in nursing is not only a question of technique and method. For
      nursing personnel to qualify as consultants they are compelled to confront its
      goals and its significance. Moreover, the part of the nurses within consultation
      must be clarified and the question of the particularities of consultation in
      nursing should be dealt with. The following article covers this subject with
      particular attention to the area of Pediatric Nursing. Long ago, job requirements
      for nursing staff in this area have involved looking not only after the sick
      child but after its entire family, too. Consultation in nursing is considered an
      independent plan designed to support the family in coping both with wellness and
      sickness and the latter's consequences. The adequate education and training will
      help nursing staff to perform these duties.

PMID- 11299669
TI  - [Scientific basis of measuring instruments in public health: on the example of
      LEP progress in the achievements of nursing].
AB  - The need for data of professional interventions in public health in general and
      in nursing in particular has risen sharply over the last years. When it comes to
      the development and the use of respective measuring instruments, their scientific
      foundation is normally called into question. The article deals with this problem
      using as an example the LEP method. The focus lies on questions of methodology
      and philosophy of science rather than questions concerning the sociology of
      organization, profession or knowledge. At first the basic problem of measurement
      in social sciences is outlined using the distinction of first and second order
      measurements. Then we introduce the construction process of LEP and show, in
      which way it links the two levels of measurement. In the following paragraphs
      questions of validity and reliability are addressed as well as the decision to
      use time as a yardstick. We then show that LEP is not a measuring method to test
      scientific hypotheses but a valid instrument constructed with the help of social
      sciences that instructs management decisions. As an information system it
      combines elements of science, practice and bureaucracy and integrates them at the
      same time. As a boundary object it provides the basis for a constructive dialogue
      between the various stakeholder groups.

PMID- 11299670
TI  - [Osteoporosis and climacteric].
AB  - The climacteric period, menopause, constitutes a physiological process in a
      woman's life which can modify her health and increase the occurrence of some
      diseases which are related to estrogen deprivation; among these, osteoporosis
      stands out. After analyzing its etiology and risk factors, the author provides a
      detailed description of various preventive measures against this disease:
      nutrition, physical exercise, healthy living habits, etc.

PMID- 11299671
TI  - [Autotransfusion with previously deposited blood units].
AB  - This article analyzes the results obtained in the development of a Prior
      Deposited Self-Transfusion Program among patients who plan to have orthopedic or
      kidney surgery. The 69 patients in this program deposited 183 blood unit, 2.6
      units/patients with a range of 1 to 5, of which 153 were transfused. The initial
      hemoglobin and hematocrit levels were 14.3 g/dl (range 11.4-16.8) and 43.3%
      (range 36-50) respectively; at the end of this self-transfusion program, these
      values were 12.4 g/dl (range 10.0-15.6) and 37.7% (range 31-48). A homologous
      transfusion was avoided in 88.4% of the cases. This Self-Transfusion Program is
      safe and effective, easy to implement, well-tolerated and can be carried out with
      an acceptable risk level for patients.

PMID- 11299672
TI  - [Physical restraint in geriatric psychology].
AB  - The use of physical restraint is a fact which we confront in everyday practice.
      The objective of this article is to establish some basic operating guidelines in
      order to prevent the use of physical restraint and which procedures to follow
      when its use is unavoidable. The authors describe some adequate instances when
      use of physical restraint may be required and they identify different methods and
      their procedures. Its use may cause a series of complications, specific risks and
      general risks, which one needs be aware of in order to prevent them. Considering
      the importance of having protocols for all these aspects in each center, the
      authors propose the contents on a clinical report sheet to facilitate a good
      control of the restraint used for each patient. This article was submitted as an
      oral report at the 8th Congress of the Catalonian-Balearic Geriatrics and
      Gerontology Association and at the 4th Conference of Current Practices in Psycho
      Geriatrics.

PMID- 11299673
TI  - PubMed, Internet Grateful Med, and Ovid: a comparison of three MEDLINE Internet
      interfaces.
AB  - Three MEDLINE Internet interfaces are compared: PubMed, Internet Grateful Med,
      and Ovid MEDLINE. Although these interfaces all search MEDLINE, significant
      differences exist in terms of their search interfaces, presentation of results,
      and special features. This paper examines these variations and explores some of
      the advantages and disadvantages of the three interfaces.

PMID- 11299674
TI  - History of medicine on the Internet: resources for librarians.
AB  - This paper offers an inventory of Internet resources on the history of medicine.
      Some sites are bibliographic; they supply book and journal citations. Some
      provide leads (or links) to more specific information, and some include full-text
      articles or historical essays. Because this material is intended to furnish
      librarians with reference direction, more attention is given to bibliographic and
      "linked" sites. This paper updates a previous version published in Medical
      Reference Services Quarterly in Spring 1998.

PMID- 11299675
TI  - HIV/AIDS and nutrition: a bibliometric analysis.
AB  - Diet and nutrition are directly involved in patient care protocols that reflect a
      shift in the treatment of HIV/AIDS as a chronic disease, with an emphasis on
      quality of life and expanded life trajectory. Research concerning HIV/AIDS and
      nutrition is multidisciplinary, yielding study results that appear in a wide
      variety of scholarly journals. The purpose of this research was to employ
      bibliometric techniques to evaluate the body of literature specific to HIV/AIDS
      and nutrition as well as to determine content overlap among major bibliographic
      citation databases.

PMID- 11299676
TI  - Toxicology and risk assessment information resources for librarians.
AB  - Many librarians work with toxicologists and risk assessors seeking information
      about chemicals and hazardous substances of concern to human health and the
      environment. Therefore, this article reviews reliable, accurate, readily
      accessible, and user-friendly sources of toxicological and risk assessment
      information. A summary and description of pertinent toxicological data,
      literature, and profile sources is presented. The majority of the resources are
      available online; however, descriptions of several important print sources are
      included.

PMID- 11299677
TI  - New reference librarians--a fresh view.

PMID- 11299678
TI  - The Cochrane Library and Cochrane Collaboration.

PMID- 11299679
TI  - Controversial issues: female genital mutilation.
AB  - As immigrant women from African countries enter the U.S., Canada, Australia, and
      Western Europe, western health care providers are beginning to see patients
      affected by the cultural practice of Female Genital Mutilation (FGM). Unfamiliar
      with the practice, either medically or culturally, these providers are turning to
      medical librarians for information. Complicating the issue are the strong
      negative feelings most western health care workers have about FGM, which appears
      to them to be both barbaric and cruel. These feelings may conflict strongly with
      those of their immigrant patients, who regard the practice as normal and
      desirable. Both medical and cultural information are needed for the professional
      to provide treatment of medical conditions, while also establishing a good
      relationship with the FGM affected patient. This article identifies and describes
      the most important refereed journal article databases, available now over the
      Internet, providing both medical and cultural information on FGM, and the most
      useful Web sites for health professionals, librarians, and interested laypersons
      who need information about this difficult multicultural issue.

PMID- 11299680
TI  - Current environment of hospital library reference: Part 1--Transition to
      technology.

PMID- 11299681
TI  - Core competencies.

PMID- 11299682
TI  - Anatomy of a stutter.

PMID- 11299683
TI  - Fortified eggs offer new reasons to shell out.

PMID- 11299684
TI  - The pill has company: the patch, the ring, the shot.

PMID- 11299685
TI  - The chemicals we harbor show that prevention pays.

PMID- 11299686
TI  - Faith and fitness meet at religious workout clubs.

PMID- 11299687
TI  - The kinesthetic speaker. Putting action into words.
AB  - Speeches and presentations offer an interesting catch-22: executives don't want
      to spend long hours creating them, and people don't want to sit for long hours
      listening to them. Ultimately, though, executives can't live without them. That's
      because a good speech or presentation has the power to inspire people to act on
      the speaker's behalf and create change. Author Nick Morgan, a longtime speech
      writer and speaking coach, says what's most often lacking in today's speeches and
      presentations is what he calls the "kinesthetic connection." Many good speakers
      connect aurally with their audiences, telling dramatic stories and effectively
      pacing their speeches to hold people's attention. Others connect visually, with a
      vivid film clip or a killer slide. Some people do both, but not many also connect
      kinesthetically. Morgan says the kinesthetic speaker feeds an audience's primal
      hunger to experience a presentation on a physical, as well as an intellectual,
      level. Through awareness of their own physical presence--gestures, posture,
      movements--and through the effective use of the space in which they present,
      kinesthetic speakers can create potent nonverbal messages that reinforce their
      verbal ones. In this article, Morgan describes techniques for harnessing
      kinesthetic power and creating a sense of intimacy with an audience--a closeness
      that is more widely expected from speakers since the advent of television. For
      instance, kinesthetic speakers should make use of audience proxies--individuals
      in the crowd who serve as representatives for the others. Ultimately, the author
      says, a speech or presentation offers something of great value to business
      executives: it's the best vehicle for winning trust from large groups of people-
      be they employees, colleagues, or share-holders.

PMID- 11299688
TI  - The 2001 HBR list. Breakthrough ideas for today's business agenda.
AB  - Business is shaped by ideas. But how do you separate enduring ideas from passing
      fancies? In this, the first edition of the annual HBR List, our editors spotlight
      five break-through ideas that are truly shaping the future of business. EVEN A
      GREAT BUSINESS MODEL IS NOT ENOUGH: The rise and fall of dot-coms left markets
      reeling and CEOs scratching their heads. The most important lesson of the
      debacle: squishy thinking about "business models" is no substitute for a
      distinctive strategy. CHANGE IS CHANGING: In recent years, pundits have urged
      executives to incite revolutions within their companies. But a growing group of
      experts now suggests that the best companies actually evolve through incremental
      change--change that builds on rather than subverts their heritage. EGO MAKES THE
      LEADER: By looking deeply into executives' psyches, we are beginning to unlock
      the enigma of leadership. While there will never be a single recipe for
      successful corporate stewardship, an understanding of the human ego can shed
      light on leadership's most fundamental components. ONLY CONNECT: In business
      organizations, what's really important about people is not their individual
      skills but the relationships they form with one another. By investing in "social
      capital," companies can often push their performance to a whole new level. THE
      BIOLOGY CENTURY DAWNS: In the twentieth century, product innovations tended to
      spring from physics. But in the new century, biology may be the central source of
      innovation. From genomics to biomimicry, the study of life promises to change
      what companies sell and even how they operate.

PMID- 11299689
TI  - The old pillars of new retailing.
AB  - Despite the harsh realities of retailing, the illusion persists that magical
      tools can help companies overcome the problems of fickle consumers, price
      slashing competitors, and mood swings in the economy. Such wishful thinking holds
      that retailers will thrive if only they communicate better with customers through
      e-mail, employ hidden cameras to learn how customers make purchase decisions, and
      analyze scanner data to tailor special offers and manage inventory. But the truth
      is, there are no quick fixes. In the course of his extensive research on dozens
      of retailers, Leonard Berry found that the best companies create value for their
      customers in five interlocking ways. Whether you're running a physical store, a
      catalog business, an e-commerce site, or a combination of the three, you have to
      offer your customers superior solutions to their needs, treat them with respect,
      and connect with them on an emotional level. You also have to set prices fairly
      and make it easy for people to find what they need, pay for it quickly, and then
      move on. None of these pillars is new, and each sounds exceedingly simple, but
      don't be fooled--implementing these axioms in the real world is surprisingly
      difficult. The author illustrates how some retailers have built successful
      operations by attending to these commonsense ways of dealing with their customers
      and how others have failed to do so.

PMID- 11299690
TI  - Is a share buyback right for your company?
AB  - Contrary to popular wisdom, buybacks don't create value by raising earnings per
      share. But they do indeed create value, and in two very different ways. First, a
      buyback sends signals about the company's prospects to the market--hopefully,
      that prospects are so good that the best investment managers can make right now
      is in their own company. But investors won't see it that way if other, negative,
      signals are coming from the company, and it's rarely a good idea for companies in
      high-growth industries, where investors expect that money to be spent pursuing
      new opportunities. Second, when financed as a debt issue, a buyback is
      essentially an exchange of equity for debt, conferring the traditional benefits
      of leverage--a tax shield and a discipline for managers. For such a buyback to
      make sense, a company would need to have taxable profits in need of shielding, of
      course, and be able to predict its future cash flows fairly accurately. Justin
      Pettit has found that managers routinely underestimate how many shares they need
      to buy to send a credible signal to the markets, and he offers a way to calculate
      that number. He also goes through the iterative steps involved in working out how
      many shares must be purchased to reach a target level of debt. Then he takes a
      look at the advantages and disadvantages of the three most common ways that
      companies make the actual purchases--open-market purchases, fixed-price tender
      offers, and auction-based tender offers. When a company's performance is lagging,
      a share buyback can look attractive. Unfortunately, a buyback can backfire-
      unless executives understand why, when, and how to use this powerful and risky
      tool.

PMID- 11299691
TI  - Future space. A new blueprint for business architecture.
AB  - Although the Internet is an essential conduit for many business activities, it
      isn't rendering the physical world any less important, as the failures of many
      Web merchants demonstrate. People need social and sensual contact. The companies
      that succeed will be those best able to integrate the physical and the virtual.
      But that requires a new kind of business architecture--a new approach to
      designing stores, offices, factories, and other spaces where business is
      conducted. The author, a faculty member at Harvard Graduate School of Design,
      provides practical guidelines to help managers and entrepreneurs think creatively
      about the structures in which their businesses operate. He outlines four
      challenges facing designers of such "convergent" structures, so-called because
      they function in both physical and virtual space: matching form to function,
      allowing visitors to visualize the presence of others, personalizing spaces, and
      choreographing connectivity. Using numerous examples, from a fashion retailer
      that wants to sell in stores as well as through a Web site to a radically new
      kind of consulate, the author shows how businesses can meet each challenge. For
      instance, allowing customers to visualize the presence of others means that
      visitors to a Web site should be given a sense of other site visitors.
      Personalizing physical and virtual spaces involves using databases to enable
      those spaces to adapt quickly to user preferences. The success of companies
      attempting to merge on-line and traditional operations will depend on many
      factors. But without a well-designed convergent architecture, no company will
      fully reap the synergies of physical space and Internet technology.

PMID- 11299692
TI  - When no news is good news.
AB  - For as long as can be remembered, BestBaby Corporation, a manufacturer of baby
      equipment and furniture, has enjoyed a solid reputation with retailers, a good
      track record with consumers, and a supportive relationship with stockholders. But
      then the child of a celebrity is injured when her stroller tips over because its
      brakes failed. The media go wild, and CEO Greg James finds himself in uncharted
      territory. The morning after the accident, Greg calls an emergency meeting of his
      executive staff. As he searches his memory to prepare for it, he thinks about
      Arzep Enterprises, BestBaby's main provider of parts and materials. He remembers
      his COO, Keith Sigismund, telling him that Arzep had switched suppliers at some
      point in order to cut its own costs. Nevertheless, Keith had assured Greg that
      the new material, although not quite as sturdy, hadn't affected the quality of
      Arzep's components. By the time the meeting is set to begin, several employees
      have threatened to quit, and stories are surfacing in the press and on the Web
      about other consumers who have had problems with their strollers. Then in the
      meeting, Keith drops a bombshell: he reads from a year-old memo sent to him by an
      employee in manufacturing stating that the new brake fittings delivered by Arzep
      don't grab the front brakes as well as the ones previously supplied. The same
      employee, and others, had complained in the past that Keith hadn't adequately
      attended to concerns they brought up to him. In this fictional case study, four
      commentators offer advice to Greg on how BestBaby should respond to the victim's
      family, the media, the public, and the company's own employees during this PR
      crisis.

PMID- 11299693
TI  - A simpler way to pay.
AB  - There have been many changes in professional services since Egon Zehnder founded
      his executive search firm nearly four decades ago--not the least of which has
      been a shift in the way professionals pay themselves. When he started,
      compensation everywhere was strongly tied to seniority. Today, partners at most
      professional services firms are paid according to the size of their client
      billings and their ability to bring in new clients. But Egon Zehnder
      International, which now has 57 offices worldwide, has stuck with the old
      fashioned way to pay. In addition to giving partners base salaries and equal
      shares in a percentage of the profit, the firm apportions another fraction of the
      profit based only on length of tenure as partner. Yet the firm attracts
      outstanding consultants, and its turnover rate is low. The reasons, the author
      says, are simple: the firm's approach to compensation forces it to hire team
      players--consultants who get more pleasure from the group's success than from
      their own advancement. And the seniority-based system requires the firm to find
      people who want to stay for the long haul. Call the system a relic, says Zehnder,
      but don't call it nonsense. It works. In this article, the author describes the
      extremely intensive interview process used to hire the right kind of people. By
      the time the interviews are over, he says, potential hires know that people in
      the firm's Boston office think and act the same way as people in its Brazil
      offices--and that they themselves must think and act that way if they are to
      succeed at the firm.

PMID- 11299694
TI  - No ordinary boot camp.
AB  - Many companies now run boot camps--comprehensive orientation programs designed to
      help new hires hit the ground running. They're intense and intimidating, and new
      employees emerge from them with strong bonds to other recruits and to the
      organization. But at Trilogy, organizational consultant Noel Tichy discovered one
      program that's a breed apart. In this article, Tichy gives us a detailed tour of
      Trilogy's boot camp, Trilogy University, to demonstrate why it's so different-
      and so effective. Like the best boot camps, it serves as an immersion in both the
      technical skills new recruits will need for their jobs and Trilogy's corporate
      culture, which emphasizes risk-taking, teamwork, humility, and a strong customer
      focus. But this is a new-employee orientation session that's so fundamental to
      the company as a whole that it's presided over by the CEO and top corporate
      executives for fully six months of the year. Why? In two three-month sessions,
      these top executives hone their own strategic thinking about the company as they
      decide what to teach the new recruits each session. They also find the company's
      next generation of new products as they judge the innovative ideas the recruits
      are tasked with developing--making the program Trilogy's main R&D engine. And
      they pull the company's rising technical stars into mentoring roles for the new
      recruits, helping to build the next generation of top leadership. After spending
      months on-site studying Trilogy University, Tichy came away highly impressed by
      the power of the virtuous teaching cycle the program has set in motion. Leaders
      of the organization are learning from recruits at the same time that the recruits
      are learning from the leaders. It's a model, he argues, that other companies
      would do well to emulate.

PMID- 11299695
TI  - Conquering a culture of indecision.
AB  - The single greatest cause of corporate underperformance is the failure to
      execute. Author Ram Charan, drawing on a quarter century of observing
      organizational behavior, perceives that such failures of execution share a family
      resemblance: a misfire in the personal interactions that are supposed to produce
      results. Faulty interactions rarely occur in isolation, Charan says. Far more
      often, they're typical of the way large and small decisions are made or not made
      throughout the organization. The inability to take decisive action is rooted in a
      company's culture. But, Charan notes, leaders create a culture of indecisiveness,
      and leaders can break it. Breaking it requires them to take three actions. First,
      they must engender intellectual honesty in the connections between people.
      Second, they must see to it that the organization's "social operating mechanisms"
      -the meetings, reviews, and other situations through which people in the
      corporation do business--have honest dialogue at their cores. And third, leaders
      must ensure that feedback and follow-through are used to reward high achievers,
      coach those who are struggling, and discourage those whose behaviors are blocking
      the organization's progress. By taking these three approaches and using every
      encounter as an opportunity to model open and honest dialogue, a leader can set
      the tone for an organization, moving it from paralysis to action.

PMID- 11299696
TI  - Six habits of merely effective negotiators.
AB  - Most executives know the basics of negotiation; some are spectacularly adept. Yet
      even experienced negotiators routinely leave money on the table, end up in
      deadlock, damage relationships, or allow conflicts to spiral. They fall prey to
      common mistakes that keep them from solving the right negotiation problem. In any
      negotiation, each side ultimately chooses between two options: accepting a deal
      or taking its best no-deal option--that is, the course of action if a deal were
      not possible. As a negotiator, you seek to advance your interests by persuading
      the other side to say yes to a proposal that meets your interests better than
      your best no-deal option. Because the other side will say yes only to a proposal
      that meets its own interests better than its best no-deal option, you must
      understand and shape your counterpart's decision so that it chooses in its own
      interest what you want. Far from being exercises in manipulation, understanding
      your counterpart's interests and shaping the decision so that the other side
      agrees to a proposal for its own reasons are the keys to jointly creating and
      claiming sustainable value from a negotiation. In this article, James Sebenius
      compares good negotiating practice with bad, providing examples from the business
      world and insights from 50 years of research and analysis on negotiation. The
      author describes six common mistakes that result in merely effective negotiation:
      neglecting your counterpart's problem, letting price bulldoze other interests,
      letting positions drive out interests, searching too hard for common ground,
      neglecting no-deal alternatives, and failing to correct for skewed vision.

PMID- 11299697
TI  - The truth about mentoring minorities. Race matters.
AB  - Diversity has become a top priority in corporate America. Despite corporations'
      best intentions, however, many have failed to achieve a racial mix at the top
      levels of management. Some have revolving doors for talented minorities,
      recruiting the best and brightest, only to see them leave, frustrated by their
      experiences. Others are able to retain high-potential professionals of color but
      find them mired in middle management. To understand the different career
      trajectories of whites and minorities, David Thomas studied the progression of
      racial minorities at three large U.S. corporations. Here, he explains the three
      career stages that all professionals advance through, and he discusses why
      promising white professionals tend to enter fast tracks early in their careers,
      whereas high-potential minorities typically take off after they have reached
      middle management. Thomas's research shows that minorities who advance the
      furthest share one characteristic: a strong network of mentors and corporate
      sponsors. He found that minorities who plateaued in middle management received
      mentoring that was basically instructional; it helped them to develop skills. By
      contrast, minorities who became executives enjoyed fuller developmental
      relationships with their mentors. Thomas explains the types of support mentors
      provide for their proteges and outlines the challenges of mentoring across racial
      lines. Specifically, he addresses negative stereotypes, public scrutiny,
      difficulty with role modeling, and peer resentment. Finally, Thomas challenges
      the notion that the job of mentors begins and ends with their one-on-one
      relationships with their proteges. He offers concrete advice on how mentors can
      support broader initiatives at their organizations to create and enhance
      conditions that foster the upward mobility of professionals of color.

PMID- 11299698
TI  - Who should pay? State committee discusses Georgia's growing indigent care
      problem.

PMID- 11299699
TI  - Pleading for help with indigent care.

PMID- 11299700
TI  - Teamwork key to our journey.

PMID- 11299701
TI  - Gainsharing arrangements revived in narrow Advisory Opinion.

PMID- 11299702
TI  - The effect of genomics on health services management: ethical and legal
      perspectives.
AB  - The growing use of genetic testing for diagnostic and predictive purposes, and
      for the purpose of selecting therapeutic regimens with better risk-benefit ratios
      for patients, raises numerous legal and ethical challenges. Researchers and
      institutional review boards must pay careful attention to the need to obtain
      informed consent from subjects. The FDA will face increased pressure to more
      carefully regulate the accuracy of genetic testing. Clinicians will need to
      safeguard the privacy and confidentiality of sensitive patient information,
      especially when testing is performed in settings in which the information may be
      readily accessible to insurers and employers. Novel genomic treatments may
      increase liability for drug manufacturers, but physicians and other healthcare
      providers, including health plans' drug formularies, will bear the primary
      liability risk. Difficult questions of distributive justice also must be faced if
      third-party payers resist covering genomic services because of their cost. Down
      the road, more aggressive gene therapy techniques and the ability to test for non
      disease traits will tax our notions of fairness, equality, and the limits of
      professional authority.

PMID- 11299703
TI  - A healthcare systems leadership perspective on organizational challenges posed by
      genomics.

PMID- 11299704
TI  - Genomics: implications for health systems.
AB  - In anticipation of and following the announcement of the completion of the
      mapping of the human genome, numerous articles have appeared in scientific,
      industry, and consumer journals and magazines on the topic of genomics. Building
      off the excitement surrounding this scientific milestone, many of these articles-
      irrespective of the audience--look to the future and anticipate how this
      knowledge breakthrough will change the way classes of diseases are diagnosed,
      treated, and even prevented over the next several generations. However,
      literature that explores the potential effect of genomics on health system care
      delivery is virtually nonexistent. As such, this article begins to prepare health
      system executives for the future by speculating how genomics may affect their
      organizations and suggesting strategies for future success.

PMID- 11299705
TI  - The economics of genomics.

PMID- 11299706
TI  - A call for fundamental change in the American healthcare system.

PMID- 11299707
TI  - Mix-up causes HIPAA data privacy rules to be re-examined.

PMID- 11299708
TI  - Speed demons.

PMID- 11299709
TI  - Let bullies beware. Politicians are going after them. But what works best?
      banishing them--or changing the culture?

PMID- 11299710
TI  - Phobias. For millions of sufferers, science is offering new treatments--and new
      hope.

PMID- 11299711
TI  - The "gang" hits again. Those famed leakey fossil hunters add a new limb to our
      family tree.

PMID- 11299712
TI  - Hormone hazards. Long-term estrogen use may double the risk of ovarian cancer.
      But look beyond the numbers.

PMID- 11299713
TI  - The new animal farm.

PMID- 11299714
TI  - The new old man.

PMID- 11299715
TI  - [Interdisciplinary cooperation in health care].

PMID- 11299716
TI  - [Interdisciplinary advanced education].

PMID- 11299717
TI  - [Full bladder and residual urine determination by ultrasound].

PMID- 11299718
TI  - [Barriers in pain relieve therapy].

PMID- 11299719
TI  - [Definition of standards, guidelines and standard nursing plans].

PMID- 11299720
TI  - Transcriptional regulation of the androgen signaling pathway by the Wilms' tumor
      suppressor gene WT1.
AB  - The androgen-signaling pathway plays a critical role in prostate cancer
      development and progression. We have recently demonstrated that the Wilms' tumor
      suppressor gene product, WT1, binds to multiple sites in the androgen receptor
      (AR) promoter and transcriptionally represses the AR gene promoter in vitro. We
      asked whether WT1 repression of the endogenous AR gene interferes in the androgen
      signal transduction cascade and modifies AR target gene expression. We analyzed
      the effect of WT1 (-/-) overexpression on an AR target gene reporter construct
      that contains the luciferase gene, the ElB TATA box, and two copies of the
      androgen-response element (ARE), the dimeric AR binding site. Luciferase activity
      was determined in 293 kidney and TM4 Sertoli cells, two nontumorigenic cell lines
      that express both AR and WT1. Cells were cotransfected by lipofectamine in the
      presence or absence of the synthetic androgen R1881. Results showed that
      overexpression of WT1 downregulates ARE-reporter gene transcription in both cell
      lines tested. The inhibitory effect of WT1 on the AR target gene construct was
      dose-dependent and androgen-independent in 293 cells, whereas in TM4 cells it was
      androgen-dependent. Additionally, a zinc-finger mutant WT1 (-/-) expression
      construct, R394W, failed to decrease luciferase activity, suggesting that WT1
      downregulates the ARE-reporter gene construct activity by directly repressing the
      endogenous AR gene promoter. Furthermore, we analyzed the expression of WT1 and
      AR mRNA in several prostate cancer cell lines in order to understand the role WT1
      may play in prostate cancer development and progression. Gel analysis of cDNA
      amplified by RT-PCR of AR and WT1 RNA from prostate cancer and non-prostatic cell
      lines showed that LNCaP and MDAPCa2b, two metastatic prostate cancer cell lines
      which are androgen-sensitive, expressed AR but not WT1. Du145 and PC3, two cell
      lines from advanced metastatic prostate cancer, which are characterized as
      androgen-independent and -insensitive, did not express AR but expressed a high
      level of WT1. Two non-prostatic cell lines, T47D and 293, weakly co-expressed AR
      and WT1. This inverse relationship between AR and WT1 expression in prostate
      cancer cell lines, together with WT1 repression of the AR promoter, suggest a
      role for WT1 in the androgen signaling pathway and in prostate cancer development
      and progression.

PMID- 11299721
TI  - The overexpression of cyclin-dependent kinase (CDK) 2 in laryngeal squamous cell
      carcinomas.
AB  - We examined the expression of CDK2 using immunohistochemistry in 102 cases of
      laryngeal squamous cell carcinomas (LSCCs). The results showed that a total of
      63.73% (65/102) patients revealed a CDK2 overexpression pattern and the CDK2
      overexpression was correlated significantly with the tumor site, tumor size and
      advanced stage. A positive correlation between the CDK2 expression and
      proliferative activity of tumor cells measured by proliferating cell nuclear
      antigen was found (r = 0.894, p < 0.0001). The Kaplan-Meier's analysis showed
      that shorter disease-free survival was significantly associated with tumor grade,
      tumor size, lymph node metastasis and advanced stage. Overall survival was
      significantly associated with tumor grade, tumor size, lymph node metastasis,
      advanced stage and CDK2 overexpression. When CDK2 and PCNA were combined, the
      patients with both CDK2 overexpression and PCNA overexpression had a poorer
      overall survival. We concluded that the CDK2 overexpression may be associated
      with the malignant biological behavior of LSCCs.

PMID- 11299722
TI  - Immunohistochemical detection of cytokeratin 18 and its neo-epitope in Warthin's
      tumor (adenolymphoma) of the parotid glands.
AB  - An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which
      reacts with the product released by cleavage of cytokeratin 18 (CK18) by
      activated caspase, was used to investigate the presence and extent of apoptosis
      in 36 cases of Warthin's tumor (WT) of the parotid glands. The distribution of
      CK18 in WT was also determined and compared with that of the product detected by
      MAb M30. In WT, CK18 was observed mainly in the tumor cells of duct-like
      structures, but not in the cells of lymphatic tissues. Positive MAb M30 reaction
      products were found in luminal contents, duct-like structures and the cytoplasm
      of some macrophages in lymphatic areas near the duct-like structures in WT. These
      findings indicated that apoptotic cells are phagocytosed and eliminated as waste
      by macrophages. It is suggested that a mechanism which regulates the balance of
      proliferative activity and apoptosis may be closely linked to the growth of WT.

PMID- 11299723
TI  - Development of a double-drug-resistant human leukemia model to cytosine
      arabinoside and L-asparaginase: evaluation of cross-resistance to other treatment
      modalities.
AB  - We have developed an in vitro model of 38 T-lymphoblastic leukemia lines
      resistant to cytosine arabinoside (ara-C) and L-asparaginase (ASNase). Of these,
      26 cell lines resistant to both drugs, 6 resistant to ara-C, and 6 resistant to
      ASNase were isolated. In 18 of these cell lines, all randomly selected,
      resistance to ara-C, ASNase and gamma radiation was documented by the MTT and
      trypan blue assays, as well as flow cytometry with Annexin V and propidium iodide
      (PI) staining. In these lines, p53, p21WAF1, and bcl-2 levels were measured by
      ELISA. Results show that P21WAF1 upregulation following p53 induction did not
      occur, suggesting that p53 function may be lost. Moreover, the data imply that
      upregulation of bcl-2 is critical in the development of resistance to ara-C and
      ASNase in these leukemic lines. In the CEM/0 parent line, p53 maintained its
      ability to interact with its DNA binding site as documented by the
      electrophoretic mobility shift assay (EMSA). But in one single- and one double
      resistant leukemic cell line examined, p53 was not shown to maintain this
      ability. We conclude that double-resistant clones to ara-C and ASNase are
      refractory to both drugs, providing an excellent leukemic model to investigate
      the multiple-drug resistance.

PMID- 11299724
TI  - Maintained CD40 and loss of polarised CD40 ligand expression in oral squamous
      cell carcinoma.
AB  - BACKGROUND: CD40 and its ligand (CD40L) are involved in immune response and
      inhibition or induction of apoptosis in different tissues. Little is known about
      CD40 and CD40L in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS:
      CD40 and CD40L were immunohistochemically evaluated in fresh-frozen samples of
      OSCC (n = 24) and normal oral epithelium (OE, n = 10). RESULTS: A high proportion
      of OE-cells expressed CD40 (> 80%) and CD40L (> 90%) in the basal compartment
      compared to less than 1% CD40-positive and 1% CD40L-positive cells in the
      suprabasal cell layer, reflecting a zonal distribution. In well-differentiated
      and moderately-differentiated OSCC, there was a less pronounced zonal
      distribution of CD40 and a marked loss of CD40L compared to OE (p < 0.05). Poorly
      differentiated OSCC maintained CD40 and markedly lost CD40L compared to OE (p <
      0.05). Double immunostaining for CD40L and laminin in OE showed a basement
      membrane associated localisation of CD40L. CONCLUSION: In OSCC, loss of polarised
      expression of CD40L and maintained expression of CD40 might be involved in
      tumourigenesis and immune evasion.

PMID- 11299725
TI  - P-glycoprotein and MRP1 expression in axillary lymph node metastases of breast
      cancer patients.
AB  - BACKGROUND: Only little information on the expression of P-glycoprotein (P-gp)
      and MRP1 in metastases of breast carcinomas is currently available. The aim of
      the present study was to investigate the expression of these two proteins in
      axillary lymph node metastases of breast cancer patients. MATERIALS AND METHODS:
      We determined the expression of P-gp and MRP1 in axillary lymph node metastases
      of 63 breast cancer patients and, in 32 patients, compared this expression to the
      expression of corresponding primary tumors. P-gp was detected by means of C219
      and Ab-2 monoclonal antibodies, and MRP1 by means of the MRPr1 monoclonal
      antibody. RESULTS: In lymph node metastases, P-gp expression was positive,
      usually at low levels, in 28 (44%) specimens whilst MRP1 expression was positive
      in all specimens with low, intermediate and high levels in 3 (5%), 46 (73%) and
      14 (22%) specimens, respectively. The percentage of P-gp expression was slightly
      lower in lymph nodes than in primary tumors while MRP1 expression showed a higher
      staining intensity in lymph nodes than in their corresponding primary tumors.
      CONCLUSION: These data indicate that both P-gp and MRP1 are frequently expressed
      in lymph node metastases of breast cancer patients and that MRP1 expression is
      more pronounced in lymph node metastases than in corresponding primary tumors.

PMID- 11299726
TI  - Induction of apoptosis by a Newcastle disease virus vaccine (MTH-68/H) in PC12
      rat phaeochromocytoma cells.
AB  - The attenuated Newcastle Disease Virus (NDV) vaccine MTH-68/H has been found to
      cause regression of various tumors including certain types of human neoplasms
      (See Table 1 and References 86-88). The mechanism of its oncolytic action is
      poorly understood, but it appears to affect specific signaling pathways in the
      target cell. We studied the cellular effects of NDV employing PC12 rat
      phaeochromocytoma cells, a widely used model system to analyze differentiation,
      proliferation and apoptosis. The MTH-68/H vaccine was found to be cytotoxic on
      PC12 cells. It caused internucleosomal DNA fragmentation, the most characteristic
      feature of programmed cell death (PCD). A brief exposure (30 min) of P12 cells to
      the virus was sufficient to produce a full-blown apoptotic response. Major
      mitogen-activated protein kinase pathways (including the stress inducible c-Jun N
      terminal kinase pathway and p38 pathway) or mechanisms regulated by reactive
      oxygen species appear to have no role in virus-induced cell death. The PCD
      inducing effect of MTH-68/H could not be prevented by simultaneous treatment of
      the P12 cells with growth factors or second messenger analogs stimulating protein
      kinase C or Ca(++)-mediated pathways. In contrast, treatment with a cyclic AMP
      analog partially protected the them from virus-induced apoptosis. These
      experimental results suggests that MTH-68/H might disrupt a growth factor
      stimulated survival pathway and that direct stimulation of protein kinase A
      catalyzed phosphorylation events bypass this NDV-induced block.

PMID- 11299727
TI  - Upregulated expression of angiogenesis genes and down regulation of cell cycle
      genes in human colorectal cancer tissue determined by cDNA macroarray.
AB  - The differential expression of hundreds of tightly, transcriptionally controlled
      genes in isolated human colorectal cancer and respective normal mucosa from two
      patients was analyzed by the cDNA macroarray technique. mRNA prepared from the
      colorectal cancer tumors was compared with 588 genes spotted onto the filter.
      Case A showed down-regulation of the expression of cell-cycle-related genes
      including cyclins, cyclin-dependent kinase (CDK) 2, and CDK-activating kinase, as
      compared with normal mucosa from the same patient. The tumors showed up
      regulation of expression of angiogenesis-related genes such as type II
      cytoskeletal 8 keratin, metalloproteinase subtypes, VEGF, and bFGF, to over 5
      fold the levels in normal mucosa. Thus, colorectal carcinoma tissues are
      characterized by the upregulation of molecules related with angiogenesis. These
      results suggest that angiogenesis-related molecules are suitable candidates for
      target-based therapies for colorectal cancer patients. In case B, the largest
      difference in expression between the tumor and mucosal tissues was observed in
      the MMP-1 gene. In contrast to the first case, there was no increase in
      expression of angiogenesis-related molecules or decrease in expression of cell
      cycle-regulatory molecules. The expression profile was quite different between
      these two patients. This approach may eventually provide a mean of selecting
      target-based drugs in individual colon cancer patients.

PMID- 11299728
TI  - Matrix proteinase inhibition by AE-941, a multifunctional antiangiogenic
      compound.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) play an important role in tissue
      remodeling under normal physiological and pathological conditions and are thus
      attractive targets for both diagnostic and therapeutic purposes. Here, we
      examined the effect of AE-941, an orally bioavailable standardized extract made
      of cartilage that shows significant antiangiogenic and antimetastatic properties
      in vivo, on the activity of various members of the MMP family. MATERIALS AND
      METHODS: The effect of AE-941 on the activity of MMPs was assessed by
      fluorimetric assays and by substrate gel zymography. RESULTS: AE-941 markedly
      inhibits the gelatinolytic activity of MMP-2 and to a lesser extent those of MMP
      1, MMP-7, MMP-9 and MMP-13. AE-941 also inhibited the elastinolytic activities of
      MMP-2 and MMP-9 as well as MMP-12 (metalloelastase), porcine pancreatic elastase
      (PPE), and human leukocyte elastase (HLE). Western blot analysis revealed the
      presence within AE-941 of immunoreactive TIMP-like proteins, suggesting that
      these proteins may be at least partly responsible for the observed MMP
      inhibition. CONCLUSIONS: Taken together, these results demonstrate that AE-941
      contains TIMP-like proteins that could be responsible for the specific inhibition
      of MMPs. Given the recent studies suggesting the presence within this compound of
      specific inhibitor(s) of endothelial cell proliferation, AE-941 appears as a
      pleotropic agent able to interfere with several biochemical steps leading to
      angiogenesis and to other physiopathological conditions. Since AE-941 is
      currently under Phase III clinical investigations, these findings are also of
      considerable importance for our understanding of its anticancer properties.

PMID- 11299729
TI  - The cytotoxicity of 1-(1-phenylalkylideneamino)-2,4-azetidinediones and their
      mode of action in human and murine tumor cells.
AB  - The 1-(1-phenylalkylideneamino)-2,4-azetidinediones are potent cytotoxic agents
      against the growth of human and murine leukemias, lymphoma, and suspended HeLa
      uterine carcinoma. In cell lines cultured from solid human tumors, the agents
      were more selective with only a few agents demonstrating significant activity
      against the growth of HCT-8 ileum adenocarcinoma, Saos-2 osteosarcoma, KB
      nasopharynx, MCF-7 breast effusion, and ovary 1-A9 carcinoma A mode of action
      study in murine L1210 lymphoid leukemia cells showed that the agents inhibited
      DNA and RNA syntheses after 60 min. The compounds were potent inhibitors of the
      de novo purine synthesis suppressing the activity of both regulatory enzymes of
      the pathway, i.e., PRPP-amido transferase and IMP dehydrogenase. In addition, the
      agents reduced the activity of ribonucleotide reductase, dihydrofolate reductase,
      RNA polymerases, and thymidine kinases as well as the reduction of d[NTP] pools.
      All of these effects would contribute to the overall reduction of DNA and RNA
      syntheses. The DNA molecule itself was not a target for the agents in that
      alkylation of nucleoide bases, intercalation between base pairs, and cross
      linking of DNA strands did not occur.

PMID- 11299730
TI  - MEK and p38MAPK inhibitors potentiate TNF-alpha induced apoptosis in U937 cells.
AB  - BACKGROUND: TNF-alpha is one of the key inflammatory cytokines and it modulates
      various events through several pathways. U937 myelomonocytic leukemia cells are
      sensitive to TNF-alpha and about 20% of these cells undergo apoptosis within 6
      hours after treatment. Co-treatment of these cells with actinomycin D or
      cycloheximide enhances TNF-alpha induced apoptosis, suggesting that some TNF
      alpha-derived signals can augment apoptosis. We investigated whether mitosis
      activating protein kinases (MAPKs) had an influence on TNF-alpha induced
      apoptosis. MATERIALS AND METHODS: U937 cells were treated by TNF-alpha with or
      without MEK or p38MAPK inhibitors. Apoptosis was assessed morphologically by
      fluorescence microscopy and caspase-3 was studied by immunoblotting. Expression
      of apoptosis-inhibitory proteins was studied by RT-PCR whilst the activation of
      JNKs was investigated by detecting their phosphorylation. RESULTS: TNF-alpha
      treatment induced apoptosis in about 23% of the cells, while pretreatment with a
      MEK inhibitor (PD98059) caused 69% of the cells to undergo apoptosis. The
      inhibition of p38MAPK by SB203580 scarcely enhanced apoptosis, although another
      p38MAPK inhibitor (PD169316) induced apoptosis in 37% of the cells. Simultaneous
      pretreatment of cells with PD98059 and PD169316 resulted in the highest level of
      TNF-alpha induced apoptosis and 90% of the cells underwent apoptosis after 6
      hours. In cells pretreated with PD98059 plus PD169316, caspase-3 was completely
      cleaved at 6 hours and early induction of c-IAP2/HIAP 1 mRNA was not observed.
      JNKs showed rapid and extensive phosphorylation in these cells. CONCLUSION: TNF
      alpha induced apoptosis was potentiated by the inhibition of either MEK alone, or
      MEK plus p38MAPK, suggesting that the MAPK pathway may be a promising target for
      cancer therapy.

PMID- 11299731
TI  - Increased sensitivity to sodium salicylate-induced apoptosis in drug-resistant
      leukemia L1210 cells.
AB  - Mouse leukemia L1210 cells selected for resistance to deoxyadenosine contain
      ribonucleotide reductase that is not feedback inhibited by dATP. These
      deoxyadenosine-resistant cells (Y8) also do not express p53 protein but do have
      WAF1 and Gadd45 mRNA and protein. The Y8 cells show increased sensitivity to DNA
      damaging agents and kinase inhibitors. In these studies we show that in the
      presence of sodium salicylate (NaSal), the parental wild-type (WT) cells block in
      G2/M phase of the cell cycle while the Y8 cells show a marked increased in the
      G0/G1 population of cells. The Y8 cells are more sensitive to apoptosis induced
      by NaSal than the WT cells. NaSal treatment causes the induction of caspase-3
      like activity in Y8 cells but no induction of caspase-3 activity in the WT cells.
      The caspase inhibitor, Ac-DEVD-CHO, decreased the percentage of Y8 cells in the
      early apoptotic fraction, but this decrease was reflected by an increase in the
      percent of cells in the late apoptotic/necrotic fraction. SB20358, a p38-MAP
      kinase inhibitor did not protect the Y8 cells from NaSal-induced apoptosis
      indicating that the p38-MAP kinase pathway was not involved in the NaSal-induced
      apoptotic pathway in the p53-independent Y8 cells.

PMID- 11299732
TI  - Expression of calretinin in human mesothelioma cell lines and cell cycle analysis
      by flow cytometry.
AB  - Human mesothelioma cell lines were studied concerning the expression of the
      calcium-binding protein calretinin (CR), and the relation of the DNA index to
      their cell cycle. The results obtained for cell lines with different
      morphological characteristics, were compared to those from human mesothelial
      cells transfected with SV40 to escape senescence. Immunocytochemical expression
      of calretinin (confirmed by immunoblot) was observed in all mesothelioma cell
      lines but not in the control cells. It is suggested that calretinin is active in
      the first steps of carcinogenesis in all human mesotheliomas and during several
      stages in the evolution towards malignancy.

PMID- 11299733
TI  - Overexpression of deletion-mutant epidermal growth factor receptor is associated
      with altered genotoxic stress-provoked p53 mRNA induction in a human glioblastoma
      cell line.
AB  - A distinct 801-bp deletion mutation of the epidermal growth factor receptor
      (EGFR) gene is frequently present in primary glioblastoma multiforme (GBM),
      confers enhanced tumorigenicity in vivo and is prognostic of a shorter interval
      to clinical relapse. This study sought to investigate whether overexpression of
      deletion-mutant (delta) EGFR affects genotoxic stress-provoked mRNA inductions of
      p53 and murine double minute 2 (MDM2), two other genes strongly involved in the
      pathogenesis of GBM. In a set of human wild-type (wt) p53 GBM cell lines (U-87MG
      and U-87MG.delta EGFR) that exclusively differ in EGFR expression (endogenous wt
      EGFR expression and exogenous delta EGFR overexpression, respectively),
      ultraviolet (UV) light irradiation-mediated EGFR, p53 and MDM2 genotoxic stress
      provoked mRNA inductions were assessed by semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) and densitometry of electrophoretically
      separated and stained RT-PCR products. Although baseline (at 0 J/m2) p53 mRNA
      expression in U-87MG.delta EGFR was 42-fold reduced, maximum p53 induction (at 8
      J/m2) amounted to 130% compared to U-87MG. Thus, ultimate UV light-mediated p53
      mRNA induction was 131.5-fold in U-87MG.delta EGFR and 2.8-fold in U-87MG. In
      contrast, neither wt/delta EGFR nor MDM2 mRNA expressions were significantly
      inducible, and MDM2 mRNA profiles were essentially the same among U-87MG and U
      87MG.delta EGFR. These data suggest that in human GBM overexpression of delta
      EGFR is associated with differential genotoxic stress-provoked p53 mRNA induction
      whereas MDM2 mRNA expression is apparently not directly affected by EGFR status.

PMID- 11299734
TI  - Novel polymorphisms in prostate specific antigen gene and its association with
      prostate cancer.
AB  - Prostate-specific antigen (PSA) is now used widely for the diagnosis and
      monitoring of patients with prostate cancer. The PSA gene is a target of the
      androgen receptor (AR) which interacts with androgen response elements (AREs) in
      the PSA gene promoter. Recently, we identified two novel polymorphisms in the PSA
      promoter ARE2 region in breast cancer. We hypothesized that some genetic
      variations might also exist in the AREs of prostate cancer, and that feature
      might correlate with cancer development and/or progression. To test this
      hypothesis, three AREs of the PSA gene promoter were characterized for 47
      prostate cancer cases and 105 controls from the Japanese population. We
      demonstrated the presence of two polymorphisms at positions -252 (G or A) and 
      205 (A or AA), which were the same as those we have found in breast cancer.
      Interestingly, the -252 A was linked with the presence of -205 AA, and the -252 G
      was always linked with the presence of -205 A. Therefore, only A-AA and G-A (-252
      -205) alleles were present in the Japanese population. The proportion of patients
      who were either heterozygotes or homozygotes for the A-AA allele was not
      significantly different from that observed among 105 individuals without cancer
      (p = 0.726). However, comparing with G-A allele homozygotes, prostate cancer
      patients carrying at least 1 A-AA alleles tended to exhibit high serum PSA levels
      (p = 0.0002), poor differentiation (p = 0.0149) and advanced clinical stage (p =
      0.0077). These results suggest that the novel polymorphisms identified in the PSA
      gene promoter may affect transcriptional activity of the PSA gene, and an excess
      of PSA production may enhance rapid progression of prostate cancer.

PMID- 11299735
TI  - Expression of the lung resistance protein in primary colorectal carcinomas.
AB  - To assess whether the lung resistance protein (LRP) is of clinical significance
      in colorectal carcinomas, we immunohistochemically determined LRP expression of
      colorectal carcinoma specimens (n = 68) by means of the monoclonal antibody LRP
      56 and compared this expression with clinical parameters. LRP expression was
      negative in 7 (10%), low in 36 (52%) and high in 25 (38%) carcinomas. LRP
      expression was independent of histological grade, tumor size, lymph node
      involvement and distant metastasis. Survival of the patients with LRP-positive
      tumors was similar to the survival of patients with LRP-negative tumors. However,
      patients with high LRP expression in their carcinomas had a prolonged survival.
      Thus LRP is frequently expressed in colorectal carcinomas and high expression
      might indicate improved survival.

PMID- 11299736
TI  - Functional suppression of integrin beta 4-mediated adhesion caused by in vivo
      sequential selection for cancer cell intravasation.
AB  - Intravasation is essential for hematogenous metastasis in cancer cells, but its
      cellular determinants have not been well elucidated because of a lack of suitable
      experimental cell systems. Int-3LL was originally developed by in vivo sequential
      selection for intravasation from Lewis lung carcinoma (3LL) cells. Here, we found
      that these variant cells showed a highly penetrating ability in vitro as well as
      an augmented intravasating potential in vivo. In three-dimensional collagen-gel,
      Int-3LL cells formed diffusive colonies with less plating efficiency than their
      parental cells. Despite these properties, Int-3LL cells showed an ability of
      invasive migration in vitro similar to parental cells. On the other hand, a
      reduced adhesiveness and less spreading on extracellular matrices were revealed
      in Int-3LL cells. Analyses using anti-integrin antibodies indicated that the
      dysadhesion phenotype in Int-3LL cells was associated with integrin beta 4
      dysfunction, which is known to produce epithelial detachment. Also, the types and
      the levels of integrins were not indistinguishable between Int-3LL and parental
      3LL cells. Thus, the impaired function of integrin beta 4-mediated adhesion is
      considered to be an important factor in intravasation during metastasis.

PMID- 11299737
TI  - Inhibitory effect of N-acetylcysteine on invasion and MMP-9 production of T24
      human bladder cancer cells.
AB  - BACKGROUND: MMPs play a crucial role in the process of cancer invasion and
      metastasis. METHODS: The influence of NAC on invasion and MMP-9 production of
      human bladder cancer cell line T24 was investigated using an in vitro invasion
      assay, gelatin zymography, Western and Northern blot analyses and RT-PCR assays.
      RESULTS: TPA increased the number of invading T24 cells through reconstituted
      basement membrane more than 10-fold compared to basal condition. NAC inhibited
      TPA-enhanced invasion dose-dependently. TPA increased the MMP-9 production by T24
      cells without altering expression of TIMP-1 gene, while NAC suppressed TPA
      enhanced production of MMP-9. Neither TPA nor NAC altered TIMP-1 mRNA level in
      T24 cells. In vitro experiments demonstrated that MMP-9 was directly inhibited by
      NAC but was not influenced by TPA. CONCLUSION: NAC limits invasion of T24 human
      bladder cancer cells by inhibiting the MMP-9 production in addition to a direct
      inhibition of MMP-9 activity.

PMID- 11299738
TI  - Apoptosis of human leukemia cells induced by Artepillin C, an active ingredient
      of Brazilian propolis.
AB  - Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is an active ingredient of
      Brazilian propolis that possesses anti-tumor activity. When Artepillin C was
      applied to human leukemia cell lines of different phenotypes, namely, lymphocytic
      leukemia (7 cell lines of T-cell, 5 cell lines of B-cell), myeloid and monocytic
      leukemia and non-lymphoid non-myeloid leukemia cell lines in vitro, Artepillin C
      exhibited potent cytocidal effects and induced marked levels of apoptosis in all
      the cell lines. The most potent effects were observed in the T-cell lines.
      Apoptotic bodies and DNA fragmentation were induced in the cell lines after
      exposure to Artepillin C. DNA synthesis in the leukemia cells was clearly
      inhibited and disintegration of the cells was confirmed microscopically.
      Apoptosis of the leukemia cells may be partially associated with enhanced Fas
      antigen expression and loss of mitochondrial membrane potential. In contrast,
      although Artepillin C inhibited the growth of pokeweed mitogen (PWM)-stimulated
      normal blood lymphocytes, it was not cytocidal to normal unstimulated
      lymphocytes. These results suggested that Artepillin C, an active ingredient of
      Brazilian propolis, has anti-leukemic effects with limited inhibitory effects on
      normal lymphocytes.

PMID- 11299740
TI  - Abrogation of G2 checkpoint specifically sensitize p53 defective cells to cancer
      chemotherapeutic agents.
AB  - BACKGROUND: Chkl is a checkpoint gene that is activated after DNA damage. It
      phosphorylates and inactivates Cdc25C at the late G2 phase. The inactivation of
      Cdc25C and consequently, the inactivation of Cdc2, are required for the G2 arrest
      induced by DNA damage. METHODS: We treated 184B5 cell line and its E6 transformed
      cell lines with adriamycin in the presence of staurosporine or UCNO1 and examined
      G2 arrest and cell death. RESULTS: We found that adriamycin induced a p53 and p21
      response as well as a G1 arrest in 184B5 cells, but not in its E6 transformed
      cells. Staurosporine or UCNO1 abrogated the G2 arrest induced by adriamycin in
      both cell lines. In addition, staurosporine or UCNO1 specifically sensitized p53
      incompetent cells to adriamycin. CONCLUSION: G2/M checkpoint abrogators can
      potentially enhance the cytotoxic effect of conventional chemotherapeutic
      reagents specifically to tumor cells.

PMID- 11299739
TI  - Correlation of immunohistochemical p53 labeling index with inhibition rate in
      chemosensitivity test in gastric and colon cancer.
AB  - To determine whether the expression of p53, p21, bcl-2 or Ki-67 in cancer cells
      is predictive of chemosensitivity, immunohistochemical examination of these
      factors and chemosensitivity assays were performed on colon and gastric cancer
      specimens. Chemosensitivity tests were performed using CDDP, 5-FU, MMC, or ADR
      and inhibition rate (IR) was calculated by MTT assay. Before exposure to
      anticancer drugs, the samples were investigated immunohistochemically for
      expression of the above factors and after anticancer drug exposure by TUNNEL
      staining, for the presence of apoptotic cells. With 5-FU and MMC, the apoptotic
      index was well correlated with IR, so their effects were related to apoptosis.
      Moreover, with these two agents, the p53 labeling index (LI) was inversely
      correlated with IR and p21-LI showed a good correlation with IR. We therefore
      concluded that immunohistochemical studies for p53 and p21 were useful for
      predicting the chemosensitivities of colon and gastric cancer to MMC and 5-FU.

PMID- 11299741
TI  - Antioxidant and free radical scavenging effects of the tannins of Terminalia
      catappa L.
AB  - Reactive oxygen species (ROS) react with biological molecules and destroy the
      structure of cells and eventually cause free radical-induced disease such as
      inflammation and cancer. Previous studies showed that an aqueus extract of
      Terminalia catappa L. exhibited superoxide radical scavenger activity and
      modification of mitomycin C-induced clasto-genicity. In order to investigate the
      multiple antioxidant effect of the tannin components of T. catappa L., their
      ability to prevent lipid peroxidation, superoxide formation and their free
      radical scavenging activity were evaluated. The results indicated that all of
      these components showed potent antioxidant activity. Punicalagin and punicalin
      were the most abundant components and had the strongest anti-oxidative effects of
      this group of tannins.

PMID- 11299742
TI  - Antitumor effects of a new lipophilic platinum compound, trans-bis(n
      valerato)(1R,2R-cyclohexanediamine)(oxalato)platinum(IV), in mice.
AB  - A new lipophilic platinum (Pt) compound, trans-bis(n-valerato)(1R,2R
      cyclohexanediamine)(oxalato)Pt(lV) (C5-OHP), was compared with cisplatin (CDDP)
      by intraperitoneal injection for antitumor activities against 3 different mouse
      models, L1210 leukemia, LMFS sarcoma with high metastatic potential and
      spontaneous mammary tumor. C5-OHP cured both CDDP-sensitive and -resistant L1210
      leukemia frequently. CDDP did not cure the leukemia, although it prolonged the
      survival of diseased mice significantly. C5-OHP cured early and advanced LMFS
      sarcomas more frequently than CDDP. Cured mice had acquired antitumor immunity,
      indicating the pivotal role of the immune system in induction of the cure of
      tumors. It is likely tllat C5-OHP can eradicate tumor cells more effectively than
      CDDP by virtue of its weaker suppressive effects on the immune system. C5-OHP but
      not CDDP could cure mammary tumors. C5-OHP manifested a curative effect against
      LMFS tumors by oral route. These results indicate that C5-OHP is a promising
      anticancer agent worthy of clinical trial.

PMID- 11299743
TI  - Bax protein expression in colorectal cancer: association with p53, bcl-2 and
      patterns of relapse.
AB  - This study evaluated the frequency and the prognostic significance of bax, bcl-2
      and p53 proteins in stage B and C adenocarcinomas of the colon and rectum.
      Paraffin-embedded specimens from 268 patients with colorectal adenocarcinomas,
      treated with surgery, were assessed; of these 160 cases were Duke's stage B and
      108 cases were Duke's stage C disease. Adjuvant chemotherapy was given to all
      stage C and to 108 out of 160 stage B cancer patients, while those having rectal
      malignancy also received pelvic radiotherapy. Duke's stage B patients were
      treated either with surgery alone or with surgery and radiotherapy. The follow-up
      period at the time of analysis ranged from 12-72 months (median 32 months).
      Immunohistochemical expression of bax, bcl-2 and mutant p53 proteins was detected
      with a frequency of 42%, 37% and 48%, respectively. However, the expression was
      strong only in 17% of tumours, on average. A strong bcl-2 expression was
      significantly associated with a strong bax expression (p < 0.0001) and with
      absence of p53 nuclear accumulation (p < 0.005). There was, however, no
      correlation between bax and p53 proteins. Furthermore, bcl-2 expression was
      significantly more frequent in grade I and 2 adenocarcinomas compared to grade 3
      disease (p = 0.01). In stage B (but not C) adenocarcinomas, bax expression was
      directly associated with higher risk of local relapse (p = 0.04). By contrast,
      cases with p53 nuclear accumulation, when they had received adjuvant
      radiotherapy, were significantly associated with a lower incidence of local
      relapse (p = 0.01), but a higher rate of distant metastasis (p = 0.06).
      Multivariate analysis for disease free and overall survival showed that bax
      expression and high Duke's stage were independent prognostic parameters
      associated with an unfavourable outcome (p = 0.009 and p = 0.0001, respectively).
      It was concluded that the immunohistochemical expression of bax is a marker of
      poor prognosis and of a higher risk of local relapse in patients with colorectal
      adenocarcinomas. p53 nuclear accumulation is associated with a better local
      control, following radiotherapy and with a metastatic phenotype. The development
      of novel monoclonal antibodies recognising specifically the mutated versus the
      wild type form of proteins would apparently improve the prognostic and predictive
      value of the immunohistochemically detected apoptotic proteins.

PMID- 11299744
TI  - Transactivation of AP-1 in AP-1-luciferase reporter transgenic mice by arsenite
      and arsenate.
AB  - Arsenic is a recognized carcinogen, which acts as a tumor promoter rather than as
      an initiator. Signal transduction pathways leading to activation of AP-1 and
      mitogen-activated protein kinases are proposed to be responsible for the tumor
      promotion activity by arsenic. Induction of AP-1 DNA binding activity and c-jun
      and c-fos expression was reported to be only observed in cells responding to
      arsenite, but not to arsenate. However, in this study, we found that both
      arsenite and arsenate could induce transactivation of AP-1 in mouse epidermal JB6
      AP-1-luciferase reporter stable transfectants, P+1-1. This induction of AP-1
      activity by arsenic appears to be through activation of mitogen-activated protein
      kinases and protein kinase C because increased AP-1 activity by arsenite could be
      blocked by either treatment of cells with PD98059 or overexpression of dominant
      negative protein kinase Ca. Furthermore, both arsenite and arsenate could induce
      transactivation of AP-1 in AP-1-luciferase reporter transgenic mice.

PMID- 11299745
TI  - Enhanced antibacterial effect of erythromycin in the presence of 3,5-dibenzoyl
      1,4-dihydropyridines.
AB  - Fifteen 3,5-dibenzoyl-1,4-dihydropyridines (BzDHP, GB1-GB15) (nifedipine (NP)
      analogs) were tested on three different E. coli strains. The compounds had
      relatively high MIC values on these strains. In combination with erythromycin
      (Er), compounds (G1,3,4,6,7,10,12) reduced MIC values of Er. When the BzDHPs were
      tested on E. coli Gy-1/Apsen.Erres strain isolated from a clinical specimen, the
      reduction of MIC values were similar to the previous strains, but not identical.
      In the polyresistant clinically isolated E. coli Gy-2/Apres.Erres strain, the MIC
      values of Er were slightly reduced in the presence of GB1-GB7. Compound GB12 was
      the most effective in enhancing the activity of Er, and was selected for plasmid
      elimination studies. However, GB12 itself had no antiplasmid effect and did not
      alter the promethazine induced plasmid elimination.

PMID- 11299746
TI  - In vitro biological activity of prenylflavanones.
AB  - The biological activity of ten prenylflavanones purified from Sophora tomentosa
      L., and Sophora moorcroftiana Benth. ex Baker (Leguminosae) was investigated. The
      flavanones with prenyl-, lavandulyl- or geranyl groups on A ring, and two
      bioactive flavonostilbenes on ring B and stilbene (resveratrol) showed tumor
      specific cytotoxic activity, antimicrobial activity, and anti-HIV activity,
      radical generation, and O2- scavenging activity. There was a positive
      relationship between radical generation and O2- scavenging activity in these
      prenylflavanones. These data suggest the medicinal significance of
      prenylflavanones.

PMID- 11299747
TI  - Tumor-specific action of sodium 5,6-benzylidene-L-ascorbate in N
      nitrosodiethylamine-administered mouse model.
AB  - In order to elucidate the mechanisms of antitumor action of sodium 5,6
      benzylidene-L-ascorbate (SBA), we established a mouse hepatocellular carcinoma
      model by oral administration of N-nitrosodiethylamine (NDA) and examined the
      ascorbate radical intensity and putrescine content in the liver. The oral intake
      of NDA induced precancerous lesion and a significant increase in putrescine
      content among three major polyamines. When the oral intake of NDA was stopped,
      morphological changes were reversed. ESR spectroscopy showed that the homogenate
      of precancerous tissues produced greater amounts of ascorbate radical than that
      of normal liver tissue. Intravenous administration of SBA 30 minutes before
      removal of the liver prolonged the higher level of ascorbate radical generation
      in the homogenate of precancerous tissue. The antitumor activity of SBA might be
      due to the long-term production of radicals in tumor tissues by its prooxidant
      action.

PMID- 11299749
TI  - Cell-specific enhancement of doxorubicin toxicity in human tumour cells by
      docosahexaenoic acid.
AB  - We examined the cytotoxicity of doxorubicin alone, or in combination with
      docosahexaenoic acid (22:6 n-3), in glioblastoma cell lines A-172 and U-87 MG and
      bronchial carcinoma cell lines A-427 and SK-LU-1. For both glioblastoma cell
      lines we found an enhanced cytotoxicity of doxorubicin when given with
      concentrations of docosahexaenoic acid that alone are non-toxic. In SK-LU-1 cells
      no such enhancement was observed, whereas a small increase was observed for A-427
      cells. The enhanced cytotoxicity in glioblastoma cells was not caused by lipid
      peroxidation products. In A-427 cells, however, the modest potentiation could be
      explained by the formation of cytotoxic lipid peroxidation products. Se
      glutathione peroxidase activity increased after doxorubicin exposure and even
      more after addition of Na-selenite, but this did not reduce the cytotoxicity of
      doxorubicin. These results demonstrated that the mechanisms of enhancement of
      cytotoxicity by docosahexaenoic acid are complex and cell-specific and do not
      require increased lipid peroxidation.

PMID- 11299748
TI  - Methylenetetrahydrofolate reductase polymorphism is associated with folate pool
      in gastrointestinal cancer tissue.
AB  - The folate pool in cancer tissue is a critical factor for the effect of 5-FU
      based chemotherapy. Methylenetetrahydrofolate reductase (MTHFR) plays a role in
      the metabolism of folate. The gene of MTHFR is polymorphic (C667T, alanine-to
      valine), and this is related to the activity of the enzyme. We analyzed the
      association between MTHFR genotype and the folate pool in gastrointestinal cancer
      tissues. MTHFR genotypes were determined in 67 surgically-resected
      gastrointestinal cancer tissues by PCR-RFLP analysis. Forty-five patients
      received no treatment and 22 patients received oral administration of UFT, a
      combination of Uridine and Tegafur, before surgery. 5,10
      Methylenetetrahydrofolate (CH2FH4) and tetrahydrofolate (FH4) were measured by
      fluoro-dUMP (FdUMP) binding assay as representative values of the folate pool.
      The number of FdUMP binding sites on Thymidylate synthase (TS) was quantified in
      the samples from UFT-administered patients. The incidences of MTHFR genotype were
      as follows: Ala/Ala, 27; Ala/Val, 30; Val/Val, 10. In the UFT(-) group, the
      amount of FH4 in Ala/Val-type cancer tissue was higher than that in Ala/Ala-type
      (1.50 +/- 1.13 versus 0.72 +/- 0.64, p < 0.05). This relationship was also
      observed on the sum of CH2FH4 and FH4 (2.88 +/- 1.85 versus 1.75 +/- 1.06, p <
      0.05). Val/Val-type cancer tissue had higher amount of either CH2FH4 and FH4 than
      Ala/Ala-type, although this finding did not reach statistical significance. In
      the UFT(+) group, no relationship between MTHFR genotype and the free folate pool
      was observed, presumably due to the influence of the amounts of FdUMP and TS in
      the tissue. The calculation of total CH2FH4 from the value of free CH2FH4, free
      TS and total TS showed a weak genotype-dependent difference in total CH2FH4. The
      TS inhibition rate also showed a weak genotype-dependent difference. These
      results suggest a link between MTHFR genotype and the folate pool in
      gastrointestinal cancer, leading to the association of MTHFR genotype with TS
      inhibition rate upon 5-FU exposure. The MTHFR genotype might be considered in the
      design of 5-FU-based chemotherapy, especially in patient-specific strategies with
      leucovorin supplementation.

PMID- 11299750
TI  - Neuron specific enolase promoter for suicide gene therapy in small cell lung
      carcinoma.
AB  - To investigate the specific transduction of a suicide gene into human small cell
      lung carcinoma (SCLC) cells, we explored the promoter region of the neuron
      specific enolase (NSE) gene as a tumor-specific promoter. In Northern blot
      analysis, NSE mRNA was expressed more abundantly in the SBC3 human SCLC cell line
      than in the RERF human SCLC cell line, the A549 human lung adenocarcinoma cell
      line and the HeLa human uterine cervix epitheloid carcinoma cell line. A
      reporting vector containing the NSE promoter (pNSE-LUC) exhibited higher
      luciferase activity in SBC3 than in the other three cell lines. After
      transfecting an expression vector containing the NSE promoter-bound HSV-TK gene
      (pNSE-TK) into the cells, we measured their sensitivity to ganciclovir (GCV). In
      SBC3, pNSE-TK transfected cells showed about the same sensitivity to GCV as non
      transfected (parental) cells. Though the NSE promoter itself is not optimal for
      use in suicide gene transfer to SCLC cells, it might be applied as a tumor
      specific promoter after enhancement of its activity.

PMID- 11299751
TI  - Heat treatment of hepatocellular carcinoma cells: increased levels of heat shock
      proteins 70 and 90 correlate with cellular necrosis.
AB  - Immunotherapy, i.e. stimulation of the body's immune response against tumor
      cells, is a promising approach in cancer treatment. In this context, heat shock
      proteins (HSP) have been shown to function in tumor antigen chaperoning. HSP are
      evolutionarily conserved and show increased expression in response to chemical
      and physical stress. Two members of the HSP family, HSP 70 and 90, seem to
      further act as immunostimulating agents because of their possible involvement in
      tumor antigen presentation. We cultured the human hepatocellular carcinoma cell
      line HepG2 and investigated its HSP content under normal and hyperthermic
      conditions. Flow cytometry showed increased levels of HSP 70 and 90 after heat
      shock at 41.8 degrees C for 60 minutes, measured after a subsequent incubation
      time of five hours, as compared to untreated cells in vitro. We further observed
      a clear correlation between the HSP 70 and 90 levels and the necrotic cell
      subpopulation in heat shocked tumor cells. We conclude that HSP expression in
      HepG2 cells can be enhanced by heat shock treatment in vitro. We suggest that
      this mechanism can be exploited in increasing tumor immunogenicity.

PMID- 11299752
TI  - Regulation of the expression of HMG1, a co-activator of the estrogen receptor.
AB  - HMG1 is a protein of high clinical significance. Besides shielding of DNA adducts
      against repair enzymes making cells more sensitive to cisplatin therapy, it is
      also a co-modulator of the activity of steroid hormone-regulated genes. Although
      HMG1 is regulated by various factors, including steroid hormone estrogen, nothing
      was known about regulatory sequences. Also the sequence of parts of HMG1
      including its promoter remains still unknown. We have completed the genomic
      organization of human HMG1 and characterized its regulatory region by luciferase
      assay for promoter activity. Insights into the regulation of HMG1 expression are
      given by the promoter analysis showing a strong functional promoter, enhancing
      and negative regulatory regions together with a CpG island in intron 1 and
      several transcription factor binding sites. Furthermore, the finding of two
      estrogen responsive elements within intron 1 is relevant as they indicate a
      direct mechanism of HMG1 up-regulation by estrogen making the presence of an
      estrogen receptor a significant marker for a combined treatment of special tumor
      types with estrogen and the anticancer drugs cisplatin or carboplatin.

PMID- 11299753
TI  - Combined use of gemcitabine and radiation in mice.
AB  - The aim of this study was to explore, in a murine tumor, if the effectiveness of
      radiation, in doses and schedules commonly used in clinical practice is
      potentiated by the combined use of the recently developed drug gemcitabine.
      Gemcitabine (30-360 mg/kg b.w.) was administered i.p. in female C3D2F1 mice
      bearing a mammary adenocarcinoma alone or combined with X-rays. Firstly,
      gemcitabine (single administration) was administered alone or at 20 min, 4 h, and
      24 h before X-ray treatments. The significant effect observed only at 24 h time
      interval, depended on the X-ray dose and not on the gemcitabine dose. Secondly, 4
      gemcitabine administrations every 3 days were used in fractionated combined
      schedules (overall treatment time of 10 days). We studied the relationship among
      different doses of gemcitabine, alone or combined with 10 daily X-ray treatments
      (2 Gy/fraction). We observed an interactive effect of gemcitabine up to its
      threshold dose of 60 mg/kg/fraction. Furthermore, 10 X-ray daily treatments and 4
      X-ray treatments every 3 days (total doses 20-40 Gy) were performed with
      gemcitabine 60 mg/kg/fraction to study the effect of different doses and
      schedules of X-rays. Tumor growth delays increase with higher X-ray doses, and
      this occurs more with 4 X-ray treatments than with 10 X-ray treatments. Our
      results re-affirm the uselessness of high gemcitabine doses, and indicate the
      effectiveness of combined gemcitabine-radiation fractionated protocols.

PMID- 11299754
TI  - Digitonin enhances the anti-tumor effect of cisplatin against methylcholanthrene
      induced rat sarcoma cells in vitro.
AB  - BACKGROUND: This study was designed to evaluate cellular uptake and cytotoxicity
      of cisplatin in methylcholanthrene (MCA)-induced rat sarcoma cells when used in
      combination with a detergent, digitonin. MATERIALS AND METHODS: In the cellular
      intake study, after MCA sarcoma cells (10(7)) were treated with cisplatin alone
      (50 micrograms/ml) and with cisplatin (50 micrograms/ml) in combination with
      digitonin at 20 microM and 50 microM, the cells were washed twice with PBS and
      the platinum levels were measured by flameless atomic spectrometry. For the anti
      tumor effect MCA sarcoma cells (10(3)) were seeded in cell culture dishes and
      loaded for 10 minutes with PBS, digitonin (5 microM), cisplatin (5 micrograms/ml)
      or a combination of cisplatin (5 micrograms/ml) and digitonin (5 microM). The
      cells were then washed and incubated for 72 hours. Bromodeoxyuridine uptake was
      measured with an ELISA system for determining viable cells counts. RESULTS: Cell
      platinum levels were significantly elevated in proportion to the increase of
      digitonin (p < 0.0001). The number of viable cells was significantly decreased
      with, the combined cisplatin (5 micrograms/ml)--digitonin (5 microM) treatment (p
      < 0.0001 CONCLUSION: Digitonin enhances the antitumor effect of cisplatin against
      methylcholanthrene-induced rat sarcoma in vitro.

PMID- 11299755
TI  - Drug resistance modification using pulsing electromagnetic field stimulation for
      multidrug resistant mouse osteosarcoma cell line.
AB  - Multidrug resistance (MDR) is one of the major problems in osteosarcoma
      chemotherapy. Therefore, methods of overcoming MDR are urgently needed. In this
      study, we investigated the effects of pulsing electromagnetic field stimulation
      (PEMFs) on a MDR murine osteosarcoma cell line which strongly expresses P
      glycoprotein (P-gp). To assess the reversal effects of PEMFs on doxorubicin (DOX)
      resistance, MTT assay was applied. Viable cells were assessed by the trypan blue
      exclusion test. Fluorescence intensity of DOX binding to nuclear DNA of each cell
      was measured using a cytofluorometer. Changes in P-gp expression in each cell
      were detected by the indirect immunofluorescence method using an antibody to Pgp.
      PEMFs increased DOX binding ability to nuclear DNA and inhibited cell growth,
      although it had no significant effect on P-gp expression. These findings
      indicated that PEMFs reversed the DOX resistance of the MOS/ADR1 cells by
      inhibiting P-gp function. The results suggested that PEMFs may be useful as a
      local treatment for MDR osteosarcoma.

PMID- 11299756
TI  - Oral administration of 1 alpha hydroxyvitamin D3 inhibits tumor growth and
      metastasis of a murine osteosarcoma model.
AB  - We studied the effect of oral administration of 1 alpha hydroxyvitamin D3 (1-D3)
      on the growth and metastatic ability of Dunn murine osteosarcoma model. A
      solution of 1-D3 or vehicle alone was administered daily for 2 weeks to tumor
      bearing mice using an esophageal tube and tumor size was serially monitored. In 1
      D3-treated mice, the growth of Dunn osteosarcoma was significantly suppressed in
      a dose-dependent manner. Histologically, tumor cells in the control mice
      proliferated in marginal regions of the tumor with wide central necrosis, whereas
      in the 1-D3-treated mice, tumor cells were distributed as scattered islands among
      extensive necrotic tissue. The mean tumor necrosis area was 55.7% in the control
      tumors and 94.6% in 1-D3-treated tumors (p < 0.001). There were no substantial
      differences in the cytofluorometric cell cycle distribution or the histological
      mitotic index between control and 1-D3-treated tumors. When 1-D3 was administered
      to mice from 2 days before to 2 weeks after transplantation of the tumor, there
      were significantly fewer metastatic foci in the lungs in 1-D3-treated mice than
      in control mice. We also tested the effect of coadministration of 1-D3 and
      doxorubicin on the growth of Dunn osteosarcoma and found that these two drugs act
      additively to suppress tumor growth. These results indicated that 1-D3 given
      orally inhibits tumor growth and metastases in a Dunn osteosarcoma model.
      Although the mechanism remains unknown, oral administration of 1-D3 might be
      promising as a new method of treating human osteosarcoma.

PMID- 11299757
TI  - Effect of combined treatment with radiation and low dose etoposide on cell
      survival.
AB  - BACKGROUND: To improve the radiotherapy results, we evaluated etoposide as an
      effective radiosensitizer by using cultured cell-lines. MATERIALS AND METHODS:
      Four cell lines having different doubling times (DT) were used: V79 (Chinese
      hamster fibroblasts, DT = 9 hours), (1), T24 (human bladder cancer, DT = 19
      hours) (2), MDA-MB231 (human breast cancer, DT = 25-30 hours) (3) and RMG1 (human
      ovarian cancer, DT = 50 hours) (4). Cell survival was determined by colony assay
      and cell cycle analysis was performed by flow-cytometry. RESULTS: The survival
      curves showed RMG1 to be the most radiosensitive, followed by MDA-MB231, T24, and
      V79. V79 was most chemosensitive to etoposide, followed by T24, MDA-MB231 and
      RMG1. Neither 24-hours exposure to etoposide (< or = 0.05 microgram/ml) or 0.5-h
      exposure (< or = 1.0 microgram/ml) had any cell killing effect on any of the cell
      lines used. When the cells were irradiated after exposure to 1 microgram/ml of
      etoposide for 0.5 hours, no radiosensitization was observed in any of the cell
      lines except V79. Enhanced radiosensitivity was observed in V79 and T24 cells
      (which have a relatively short DT) when they were incubated with 0.05
      microgram/ml etoposide for 24 hours but no enhanced effect was seen in MDA-MB231
      or RMG1 cells (which have a relatively long DT). CONCLUSION: It is suggested that
      a combination of radiation and etoposide may be useful in the treatment of
      rapidly growing cancer.

PMID- 11299758
TI  - Adenovirus-mediated suicide gene transfer to small cell lung carcinoma using a
      tumor-specific promoter.
AB  - The gastrin-releasing peptide (GRP) is expressed in most types of small cell lung
      carcinoma (SCLC) and the GRP promoter is thought to be potentially useful for
      tumor-specific expression of the suicide gene in SCLC. We constructed an
      adenovirus containing the herpes simplex thymidine kinase suicide gene driven by
      the GRP promoter (AdGRP-TK) and transfected it into GRP-expressing SCLC cells
      (SBC5) to confer sensitivity to ganciclovir (GCV). After infection with AdGRP-TK,
      SBC5 cells became more sensitive to GCV in vitro. In nude mice, a subcutaneously
      inoculated tumor of SBC5 cells infected with AdGRP-TK in advance regressed
      completely after intraperitoneal administration of GCV. These results suggest
      that adenovirus-mediated gene transfer of the suicide gene followed by pro-drug
      treatment may be applicable to SCLC.

PMID- 11299759
TI  - Cyclin-dependent kinase-inhibitor 1 (CDKN1A) in the squamous epithelium of the
      oropharynx: possible implications of molecular biology and compartmentation.
AB  - The cdknlA gene encodes CDKN1A, a protein that regulates cell cycle progression,
      terminal differentiation, and apoptosis. Polymorphisms or loss of heterozygosity
      of this usually biallelically expressed gene have no major impact on
      carcinogenesis. The prevalence of somatic mutations in malignancies is low. Gene
      rearrangements involving cdknlA are scarce. CDKN1A is expressed in both
      premalignant and malignant lesions. While the prognostic value of nuclear CDKN1A
      expression is controversial, the prognostic value of its recently discovered
      cytoplasmic accumulation is simply unknown. CDKN1A translocates from the nucleus
      to the cytoplasm when cleaved by caspase-like activities during early apoptosis.
      The presence of cytoplasmic catabolites (e.g.: p14) might therefore indicate
      apoptosis. We found no correlation between nuclear and cytoplasmic anti-CDKN1A
      immunoreactivity in our samples of oropharyngeal squamous cell carcinoma. CDKN1A
      Cap20, CDKN1, CDKN1A, CDKNA1, Cip-1, Mda-6, P21, Pic1, Sdi-1, Waf-1.

PMID- 11299760
TI  - Different effects of valproic acid on proliferation and migration of malignant
      glioma cells in vitro.
AB  - Valproic acid (VPA) has been considered as a possible treatment agent for
      malignant gliomas. In order to characterise the possibilities of VPA, we
      investigated the effects on cell migration and proliferation. Human cell lines
      T98G, A172, 85HG66 and 86HG39 were treated with VPA or left untreated, afterwards
      Boyden chamber assay was used for measuring vertical migration. In a second assay
      cells were stimulated to create spheroids and spheroid migration was measured.
      Proliferation was assessed using a cell counter. VPA decreased proliferation of
      86HG39 > A172 > 85HG66 cells, whereas T98G remained uninfluenced. The influence
      of VPA on migration was different; whereas VPA dose-dependently stimulated
      migration of 86HG39 cells, migration of T98G and 85HG66 decreased, whereas A172
      cells remained uninfluenced. Only 86HG39 and A172 cells created spheroids. In
      both cell lines Boyden-chamber-findings were confirmed by analysing the influence
      of VPA on spheroid migration. These non-uniform data demonstrate that the benefit
      of VPA in glioma treatment is not clear and needs further investigation.

PMID- 11299761
TI  - Differences in thermostability of thymidine kinase isoenzymes in normal ovary and
      ovarian carcinoma.
AB  - Thymidine kinase 1 (TK 1 EC. 2.7.1.21) the most specific and cell-cycle regulated
      salvage enzyme for pyrimidine nucleoside supply of DNA synthesis is a promising
      target to rationally designed chemo- and other therapies. The present study was
      undertaken to compare the heat stability of TK isoenzymes of both normal ovarian
      and epithelial ovarian cancer cells. Tissue extracts of epithelial ovarian
      carcinomas (N = 7) and normal ovaries (N = 9) were analyzed for thymidine kinase
      activity using the polyethyleneimine-cellulose disc radioassay. The TK activity
      in extracts of ovarian carcinomas was 12-fold higher than in extracts of normal
      ovaries. The TK activity of ovarian carcinomas decreased significantly even after
      30 minutes incubation at 37 degrees C while, the enzyme activity of normal
      ovarian extracts was more stable and decreased to the same extent after 120
      minutes. The half-life time of the enzyme activity was 82 min in the normal but
      only 36 minutes in the cancer tissue extract at 37 degrees C. CONCLUSION: The TK
      activity of malignant ovarian cells was much higher but more unstable (t1/2 = 36
      minutes) than the enzyme isolated from healthy ovaries (t1/2 = 82 minutes). This
      profound difference in thermostability might provide the molecular background for
      hyperthermia combined with chemotherapy as a promising treatment for ovarian
      malignancies.

PMID- 11299762
TI  - IGF-II down regulation associated cell cycle arrest in colon cancer cells exposed
      to phenolic antioxidant ellagic acid.
AB  - Altered cell and tissue differentiation is characteristic of premalignant lesions
      long before they become invasive and metastatic. One approach to controlling
      preneoplastic lesions is to block their expansion with non-toxic agents that
      suppress cell proliferation and induce apoptosis. Here, we show that ellagic
      acid, a natural, dietary phenolic antioxidant when given at 10(-5) M for 48 hours
      to colon cancer cells (SW 480), induced down regulation of insulin like growth
      factor IGF-II, activated p21(waf1/Cip1), mediated a cumulative effect on G1/S
      transition phase and caused apoptotic cell death. SW480 colon cancer cells
      expressed significant mRNA levels for the mitogenic insulin like growth factor
      (IGF-II). Collectively, these observations suggest that growth inhibition by
      ellagic acid is mediated by signaling pathways that mediate DNA damage, triggers
      p53, which in turn activates p21 and at the same time alters the growth factor
      expression, resulting in the down regulation of IGF-II.

PMID- 11299763
TI  - Construction of an expression cassette with hTNF-alpha gene for transient
      expression of the gene in mammalian cells.
AB  - BACKGROUND: Tumor vaccines, which are created by the insertion of cDNA encoding
      different cytokines into the tumor cells, are capable of inducing a very complex
      immune reaction including activation of CD8 T cells, granulocytes, macrophages,
      the triggering of cytokine cascades and antibody production. Aiming to create
      genetically modified tumor cells which could produce and secrete Human Tumor
      Necrosis Factor-alpha (hTNF-alpha), we constructed the expression cassette
      containing hTNF-alpha gene in pcDNA3 plasmid vector. MATERIALS AND METHODS: The
      successful ligation of cDNA encoding for hTNF-alpha into pcDNA3 plasmid vector
      was confirmed by PCR, restriction mapping and sequence determination. The
      constructed expression cassette in pcDNA3 vector was than transferred in vitro
      into malignant melanoma B16 tumor cells by the method of Receptor Mediated Gene
      Transfer (RMGT). RESULTS: Measurable amounts of hTNF-alpha protein detected in
      the medium of transfected cells proved that tumor cells modified in this manner
      became producers of hTNF-alpha protein. CONCLUSION: The expression of the
      transferred gene was transient and the produced protein was biologically active.
      Furthermore, the production of hTNF-alpha protein was also observed in sub
      lethally irradiated tumor cells, showing that the expression cassette was
      preserved during the irradiation and that the cells were potentially applicable
      as a tumor vaccine.

PMID- 11299764
TI  - Breast carcinoma cell uptake and biodistribution of technetium-99m-carboxymethyl
      benzylamide dextran.
AB  - Carboxymethyl Benzylamide Dextran (CMDB7) displayed an in vitro growth inhibitory
      activity on breast tumor cells. CMDB7 is able to disrupt the interaction of
      angiogenic growth factors (FGF2, TGF beta and PDGF) with their membrane
      receptors. This compound blocks the angiogenesis of MDA-MB435 carcinoma
      xenografted in mammary fat pad and their lung metastases in nude mice. In this
      work, we studied the uptake of CMDB7 labeled with 99mTc in cultured human breast
      cancer MCF-7 cell line and the highly tumorigenic MCF-7ras cell line (Ha-ras
      transfected MCF-7 cells) and the in vivo distribution in MCF-7ras tumor-bearing
      mice. The 99mTc-CMDB7 are stable and the intracellular concentration is time
      dependent and reaches a plateau at 180 minutes. 99mTc CMDB7 uptake is much higher
      in MCF-7ras cells than MCF-7 cells. Since CMDB7 is internalized and could also
      inhibit cell proliferation by acting at nuclear sites, we investigated the MCF
      7ras nuclear localization after cell fractionation. Cell fractionation revealed a
      cytoplasmic and nuclear internalization of CMDB7. The tumor uptakes of 99mTc
      CMDB7 were 0.34%, 0.72% and 0.62% of the administrated doses per gram of tumor
      tissue at 1 hour, 3 hour and 5 hours respectively after their injection. The
      blood clearance of 99mTc CMDB7 was very rapid and the liver, spleen and kidney
      uptakes were very weak. These results confirm the absence of toxicity of CMDB7
      and the usefulness of CMDB7 in cancer therapy by targeting breast tumors.

PMID- 11299765
TI  - Immunolocalization of p53, glutathione S-tranferase pi and CD57 antigens in oral
      leukoplakia.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the relationship
      between histological epithelial dysplasia, the immunolocalization of p53 and
      glutathione S-transferase pi on the immunolocalization of the CD57 antigen.
      MATERIALS AND METHODS: Seventy biopsies were included in the study and the
      streptavidin-biotin-peroxidase method was used to detect the antigens. RESULTS:
      The results demonstrated a significant relationship between p53, GST-pi positive
      staining with moderate/severe epithelial dysplasia. There was no relationship
      between p53 and GST-pi. The mean number of CD57+ lymphoid cells was higher in the
      lesions with increased epithelial dysplasia and positive for GST-pi. No
      difference was found regarding CD57 immunolocalization in leukoplakias positive
      and negative for p53. CONCLUSIONS: As the presence of CD57+ lymphoid cells are
      indicative of immunosuppression, our study suggests that the severity of
      epithelial dysplasia and positive immunolabelling for GST-pi are associated with
      local immune response alterations in oral leukoplakias. Our data also give
      support to the idea that GST-pi and p53 are not time-point related during oral
      cancer development.

PMID- 11299766
TI  - Expression of the RB protein, allelic imbalance of the RB gene and amplification
      of the CDK4 gene in metaplasias, dysplasias and carcinomas in Barrett's
      oesophagus.
AB  - In the present study, the role of allelic loss at the retinoblastoma gene (RB),
      expression of the retinoblastoma protein (pRb) and amplification at the CDK4 gene
      in the metaplasia--dysplasia--carcinoma sequence in Barrett's oesophagus (BO) was
      investigated. Samples of metaplastic specialised epithelium (SE; n = 28), low
      grade dysplasia (LGD; n = 21), high-grade dysplasia (HGD; n = 19) and invasive
      adenocarcinoma (CA; n = 35) derived from 36 oesophagectomy specimens were
      included. Of the cases that were informative for the RB gene (n = 27), loss of
      heterozygosity (LOH) was found in none of the 22 SE, in none of the 14 LGD, in 1
      of the 12 HGD (8.3%) and in 5 of the 27 CA (18.5%). Immunohistochemically, an
      enhanced expression of pRb protein in LGD, HGD and CA as compared with SE was
      found in most cases. In 4 carcinoma samples, however, a marked reduction (3
      cases) or complete absence (1 case) of pRb protein expression was found. Two out
      of these 4 CA samples showed LOH in the RB gene whilst one case was heterozygous
      and one case was homozygous. In contrast to the positive controls used, CDK4
      amplification was not detectable by means of differential PCR in any of the
      samples under investigation. The present study indicated that allelic loss of the
      RB gene occurs late in the metaplasia--dysplasia--carcinoma sequence in BO.
      Immunohistochemically determined loss of pRb protein expression may indicate LOH
      of the RB gene. CDK4 gene amplification does not seem to play a role in the
      development of oesophageal adenocarcinoma.

PMID- 11299767
TI  - Inhibition of NF-kappa B with proteasome inhibitors enhances apoptosis in human
      lung adenocarcinoma cells in vitro.
AB  - BACKGROUND: Nuclear factor-kappa B (NF-kappa B) nuclear translocation has an
      important role in preventing apoptotic cell death in some cancers. However,
      little is known about the role of NF-kB in non-small cell carcinoma. MATERIALS
      AND METHODS: Human lung adenocarcinoma cells were stimulated with tumor necrosis
      factor (TNF) alone or TNF with proteasome inhibitors to block NF-kappa B
      translocation. Cytotoxicity assays, histone-associated DNA-fragmentation ELISA,
      immunoblots of poly-(ADP ribose)-polymerase (PARP) and electron microscopy were
      used to evaluate apoptosis. RESULTS: TNF induced I kappa B proteolysis and NF
      kappa B nuclear translocation; however, this was blocked by pretreatment with
      proteasome inhibitors. TNF alone was not cytotoxic, but when NF-kappa B was
      blocked TNF induced cell death. Specifically, the cytotoxicity was due to
      apoptosis as noted by increased DNA-fragmentation, degradation of PARP and
      characteristic morphology. CONCLUSIONS: Proteasome inhibition was an effective
      method to inhibit NF-kappa B activation in lung adenocarcinoma cells. TNF in
      conjunction with. NF-kappa B inhibition was a potent stimulus for apoptosis.

PMID- 11299768
TI  - Effects of selenium supplementation on malignant lymphoproliferative pathologies
      associated with OF1 mouse ageing.
AB  - Low plasma selenium (Se) levels have been shown to correlate with increased
      cancer incidence in humans and in mice. This study was undertaken to investigate
      the ability of Se to decrease mortality rate and tumor production in ageing mice.
      Se (2.5 ppm) given as sodium selenite in drinking water to 8 months old OF1 mice,
      for 4 consecutive months, reduced significantly the mortality of mice with 6% and
      50% mortality rate for Se and control groups, respectively. In addition 80% of
      control deaths resulted from a lymphoid cell neoplasma, while no one of Se
      supplemented mice produced tumor. Evaluation of parameters of free radical
      metabolism showed highly significant reduction of the antioxidant defence system
      in the liver of cancer mice, with a 78% decrease in GSH-Px activity, a 65%
      decrease in superoxide dismutase (SOD) activity, a 75% decrease in the GSH/GSSG
      ratio and a 62% decrease of plasma Se level, as compared to healthy old mice.
      Nevertheless in the conditions of our experiment, Se didn't really improve the
      endogenous antioxidant status of ageing mice.

PMID- 11299769
TI  - Mechanism of differential sensitivity to cisplatin in nasopharyngeal carcinoma
      cells.
AB  - Cisplatin is used in the treatment of many tumours, including nasopharyngeal
      carcinoma (NPC). In this study, we studied two nasopharyngeal cancer cell lines
      with a four-fold difference in sensitivity to cisplatin. Following exposure to
      cisplatin, the sensitive SUNE1 cell line underwent apoptosis while the relatively
      resistant CNE1 line died through mitotic cell death. No differences were seen in
      telomere length or in the cell cycle distribution after cisplatin treatment.
      However, there was an increase in Bax levels in the sensitive cell line SUNE1,
      while in the resistant line CNE1 that did not undergo apoptosis, Bax levels fell.
      Our results suggest that upregulation of Bax is associated with the sensitivity
      of these NPC cells to cisplatin.

PMID- 11299770
TI  - Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal
      antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer.
AB  - The purpose of the present study was to compare the therapeutic efficacy of the
      alpha-emitter Astatine-211 with the beta-emitter Iodine-131 bound to the specific
      monoclonal antibody MOv18. The measurements were performed in an ovarian cancer
      cell line (NIH:OVCAR 3) growing intraperitoneally in nude mice. Two weeks after
      the intraperitoneal inoculation of 1 x 10(7) cells of the human ovarian cancer
      cell line NIH:OVCAR-3 twenty mice were treated intraperitoneally with the
      specific monoclonal antibody MOv-18 labelled with either 211At (310-400 kBq) or
      131I (5100-6200 kBq). The pharmacokinetics and biodistribution of labelled
      antibody in tumour-free animals were studied and the resulting bone marrow dose
      was estimated. When the mice were treated with 211At-labelled antibody 9 out of
      10 mice were free of macro- and microscopic tumour compared to 3 out of 10 when
      Iodine-131 was used. The equivalent dose to the bone marrow was 2.4-3.1 Sv from
      211At- and 3.4-4.1 Sv from 131I-irradiation. The therapeutic efficacy of 211At
      labelled specific antibody is very good and, at approximately equivalent bone
      marrow doses, better than that of 131I.

PMID- 11299771
TI  - Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK
      regulators and ERK MAP kinase activation in breast carcinoma cells.
AB  - We have previously reported that apigenin inhibits the growth of thyroid cancer
      cells by attenuating epidermal growth factor receptor (EGF-R) tyrosine
      phosphorylation and phosphorylation of ERK mitogen-activated protein (MAP)
      kinase. In this study, we assessed the growth inhibitory effect of apigenin on
      MCF-7 breast carcinoma cells that express two key cell cycle regulators, wild
      type p53 and the retinoblastoma tumor suppressor protein (Rb), and MDA-MB-468
      breast carcinoma cells that are mutant for p53 and Rb negative. We found that
      apigenin potently inhibited growth of both MCF-7 and MDA-MB-468 breast carcinoma
      cells. The approximate IC50 values determined after 3 days incubation, were 7.8
      micrograms/ml for MCF-7 cells, and 8.9 micrograms/ml for MDA-MB-468 cells,
      respectively. Because the cell cycle studies using FACS showed that both MCF-7
      and MDA-MB-468 cells were arrested in G2/M phase after apigenin treatment, we
      studied the effects of apigenin on cell cycle regulatory molecules. We observed
      that G2/M arrest by apigenin involved a significant decrease in cyclin B1 and
      CDK1 protein levels, resulting in a marked inhibition of CDK1 kinase activity.
      Apigenin reduced the protein levels of CDK4, cyclins D1 and A, but did not affect
      cyclin E, CDK2 and CDK6 protein expression. In MCF-7 cells, apigenin markedly
      reduced Rb phosphorylation after 12 h. We also found that apigenin treatment
      resulted in a dose- and time-dependent inhibition of ERK MAP kinase
      phosphorylation and activation in MDA-MB-468 cells. These results suggest that
      apigenin is a promising antibreast cancer agent and its growth inhibitory effects
      are mediated by targeting different signal transduction pathways in MCF-7 and MDA
      MB-468 breast carcinoma cells.

PMID- 11299772
TI  - Detection of circulating breast cancer cells with multiple-marker RT-PCR assay.
AB  - RT-PCR assay for multiple markers has been shown to increase the detection rate
      of circulating tumor cells. This assay targeted against cytokeratin 19 (CK19),
      cytokeratin 20 (CK20) and beta-subunit of human chorionic gonadotropin (beta-hCG)
      was used to detect circulating breast cancer cells. 5 ml of peripheral blood was
      drawn before any surgical procedures from 72 breast cancer patients and 30 cases
      with benign breast disease. Total RNA was extracted from peripheral blood
      mononuclear cells, reverse-transcripted and amplified. For the benign cases, 10%
      (3/30) were positive for CK19 and all were negative for CK20 and beta-hCG,
      whereas 9.72% (7/72), 2.78% (2/72) and 12.5% (9/72) of the malignant cases were
      positive for CK19, CK20 and beta-hCG respectively. The detection rate of
      circulating breast cancer cells was unchanged when CK19 was combined with CK20,
      but it increased to 18.1% (13/72) when the marker was combined with beta-hCG. A
      significant difference was observed for beta-hCG between benign cases and
      affected patients with stage II, III and IV disease (p = 0.026). In conclusion,
      positive RT-PCR signals in blood samples of affected patients correlated with
      stage, in particular for beta-hCG. CK19/beta-hCG was a promising marker
      combination.

PMID- 11299773
TI  - Correlation between mRNA levels of IL-6 and TNF alpha and progression rate in
      anal squamous epithelial lesions from HIV-positive men.
AB  - BACKGROUND: The incidence of anal high-grade intraepithelial lesions (HSILs) and
      progression of anal low-grade intraepithelial lesions (LSILs) to HSIL are high in
      HIV-positive men. Endogenous cytokines might support the pathogenesis of this
      progression. MATERIALS AND METHODS: Accordingly, we determined mRNA levels of IL
      6 and TNF alpha and their receptors together with viral genes (HIV-gag and HPV
      E7) in biopsies of anal condylomas, LSILs and HSILs from HIV-positive individuals
      by a semiquantitative RT-PCR method. RESULTS: We found that HSIL significantly
      differs in expression of these genes from LSIL and condylomas, and the latter two
      lesions were virtually undistinguishable from each other. A correlation between
      cytokine levels and HIV as well as HPV E7 transcripts suggests that changes might
      be associated with each other. CONCLUSIONS: These findings reveal important
      molecular events associated with progression of anal intraepithelial lesions
      (ASILs) in HIV-infected men.

PMID- 11299774
TI  - Low density lipoprotein receptor and mRNA expression in human colorectal cancer.
AB  - BACKGROUND: We have previously show that, 63.3% of colorectal cancers did not
      express the Low Density Lipoprotein Receptor (LDLR). We now report the findings
      of a study on the expression of LDLR and its mRNA in neoplastic tissue specimens
      of human colorectal cancer (CRC), carried out to verify whether the absence of
      the LDLR in these tumours is reflected by the absence of its transcript.
      MATERIALS AND METHODS: 32 patients (10 females and 22 males) operated for CRC
      were included in the study. The LDLR levels were evaluated by immunoenzymatic
      assay. The LDLR-mRNA, reverse-transcribed and then amplified by polymerase chain
      reaction, was detected by chromatography. RESULTS: The LDLR protein was present
      in 12 out of the 32 patients. LDLR-mRNA expression was detected in 17 out of the
      32 patients. The absence of the LDLR protein was reflected by the absence of its
      transcript in 13 out of the 20 tumours; The LDLR mRNA levels were significantly
      higher in the tumours that did not expres LDLR. CONCLUSION: The variable
      expression of the LDLR protein and LDLR mRNA in CRC detected in this study
      suggests the possibility that different therapeutic strategies may be indicated
      for these tumours.

PMID- 11299775
TI  - v-FBR-fos oncogene fails to rescue mammalian cells from growth arrest but affects
      the responses of human fibroblasts to heparin.
AB  - The effects of v-fos oncogene on the proliferation of mammalian cells were
      studied using several approaches. Constitutive overexpression of v-FBR-fos in
      normal human fibroblasts (MRC-5) and of v-FBR-fos in human chondrocytes (HAC21)
      failed to immortalise them, extend their in vitro lifespan, increase their growth
      rates or induce cellular transformation. Further, v-FBR-fos did not render MRC-5
      growth factor-independent or alter their responsivenness to serum, but it
      markedly suppressed their heparin-induced proliferation. A conditionally
      immortalized, temperature-sensitive rat embryo fibroblast cell line (tsa14) which
      undergoes growth arrest upon inactivation of a thermolabile SV40 large T antigen
      by a temperature shift producing a phenotype that mimmicks the senescent
      phenotype, was also used to study the effects of v-FBR-fos on cell proliferation.
      Whereas a wild-type SV40 large T antigen rescued tsa14 from a temperature
      dependent growth arrest, v-FBR-fos failed to do so. Hence, v-FBR-fos was not
      sufficient to, at least, complement the tsa14 growth defect. There was no change
      in the expression of c-jun and junB, members of the AP-1 transcriptional complex
      in MRC-5v-fos cells. These data show that v-FBR-fos is not sufficient to rescue
      mammalian cells from senescence but it can affect the responses of human
      fibroblasts to heparin suggesting a role of fos in cell proliferation.

PMID- 11299776
TI  - Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or
      intralipid.
AB  - Clinical applications of the first-generation multidrug resistance (MDR)
      modulators, such as cyclosporin A (CsA) have been hampered because of their
      severe side effects in vivo. In this study, we utilized liposomes and Intralipid
      to provide selective delivery of CsA to tumor cells as well as to circumvent
      toxicities associated with CsA by altering the pharmacodistribution properties of
      encapsulated CsA. The MDR reversing effect of CsA in free, liposomal or
      Intralipid formulations on the uptake and transport of epirubicin in Caco-2 cells
      and rat intestines was evaluated. The results showed that CsA in free or
      liposomal formulations significantly enhanced the intracellular accumulation of
      epirubicin in a dose-related fashion in Caco-2 cells, with the highest
      enhancement at 2 microM: These formulations substantially ameliorated the apical
      to basolateral absorption of epirubicin in Caco-2 cells and markedly increased
      mucosal to serosal absorption of epirubicin in rat jejunum and ileum. CsA in
      free, liposomal or Intralipid formulations all significantly reduced basolateral
      to apical efflux of epirubicin across Caco-2 monolayers. CsA encapsulated in
      liposomes showed greater enhancement than other formulations. In conclusion,
      liposomal preparations of CsA may circumvent MDR and have the advantage of
      diminishing side effects, thus providing a useful alternative dosage form for
      intravenous administration of CsA to be combined with cytotoxic agents for the
      treatment of resistant tumors.

PMID- 11299777
TI  - Expression of neutrophil collagenase (MMP-8) in Jurkat T leukemia cells and its
      role in invasion.
AB  - BACKGROUND: Previous studies have shown that MMP-8, the neutrophil collagenase,
      was expressed in neutrophils, chondrocytes and rheumatoid synovial fibroblasts.
      MATERIALS AND METHODS: We used semi-quantitative RT-PCR analysis, Western
      blotting, and immunofluorescence assays to determine the expression of MMP-8 in
      Jurkat T cells. RESULTS: We have determined the expression of MMP-8 from Jurkat
      cells and the down-regulation of its expression by genistein, a principal soy
      isoflavone. Genistein inhibited the invasion of Jurkat cells through a model
      basement membrane by about 75%, similar to the inhibition by BB-94, a synthetic
      MMP inhibitor. Genistein also down-regulated the expression of MMP-13, but
      slightly up-regulated the expression of TIMP-1 and TIMP-2. CONCLUSIONS: Our
      findings documented for the first time the expression of the neutrophil
      collagenase by a T-cell line. We also determined the inhibition of Jurkat cell
      invasion by genistein, which was in part mediated through the regulation of the
      expression of MMPs and TIMPs.

PMID- 11299778
TI  - Expression of tenascin and fibronectin in benign epithelial hyperplastic lesions
      and squamous carcinoma of the larynx.
AB  - BACKGROUND: Tenascin (T) and fibronectin (FN) are glycoprotein components of the
      extracellular matrix presumably involved in cancer progression. We analyzed their
      expression in epithelial hyperplastic lesions (EHL) and squamous carcinoma (SC)
      of the larynx. MATERIALS AND METHODS: Samples from resected larynges of 30
      patients with SC, and laryngeal biopsies of 28 patients with EHL, SC or benign
      reactive conditions were included. Immunohistochemistry was performed with
      antibodies against T and FN. RESULTS: T and FN gradually increased with the grade
      of EHL and were markedly increased in the majority of SC. In SC, expression of T
      and FN correlated with the degree of desmoplasia but was inversely related to the
      density of lymphocytic stromal infiltration and the differentiation of SC. T and
      FN were also positive in benign reactive conditions. CONCLUSION: T and FN
      immunostaining provides useful information on epithelial-stromal interaction in
      laryngeal EHL and SC but should not be regarded as a reliable stromal marker of
      malignancy. Our results supported the postulated diversified nature of the tumor
      stroma.

PMID- 11299779
TI  - Correlation of in vitro cytotoxicity and clinical response to chemotherapy in
      ovarian and breast cancer patients.
AB  - During the last years, a number of assays have been developed aiming at
      predicting the most effective chemotherapy regimen for each individual, avoiding
      possible toxicity of ineffective drugs. In the present study we have used an in
      vitro chemosensitivity/chemoresistance assay in order to evaluate cytotoxic
      treatment in ovarian and breast cancer patients. The assay was applied in 77
      ovarian and breast cancer samples and the observed in vitro responses to various
      chemotherapeutic drugs or combinations of drugs were then correlated to the in
      vivo responses and the overall clinical data of the examined patients. Direct
      comparison was possible for 25 cases. The overall positive predictive value of
      the assay was 50% and the negative predictive value was 57%. However, it was
      observed that the positive predictive value for ovarian patients was 69% and that
      the negative predictive value for breast patients was 100%. Therefore this study
      indicates that although in vitro chemosensitivity/chemoresistance is a valuable
      assay, further analysis and implications of other factors are required for a
      general evaluation of cytotoxic treatment for patients with ovarian and breast
      cancer.

PMID- 11299780
TI  - Micronucleus formation in human lymphocytes and in the metabolically competent
      human hepatoma cell line Hep-G2: results with 15 naturally occurring substances.
AB  - To examine the concordance of two metabolizing systems for use in genotoxocity
      testing with the micronucleus test, 15 naturally occurring substances (arecoline,
      the plant extract aristolochic acid, beta-asarone, benzyl acetate, coumarin,
      emodine, isatidine dihydrate, monocrotaline, psoralen, reserpine, retrorsine,
      safrole, sanguinarine chloride, tannin and thiourea) were tested for their
      genotoxicity in the cytokinesis-block micronucleus test in vitro with human
      lymphocytes and in the presence and the absence of an exogenous metabolizing
      system from rat liver S9-mix and the metabolically competent human hepatoma cell
      line Hep-G2. Arecoline, the plant extract aristolochic acid, psoralen and tannin
      caused a significant increase in the number of micronuclei in human lymphocytes
      in the presence and the absence of an exogenous metabolising system from rat
      liver S9-mix and the metabolically competent human hepatoma cell line Hep-G2. A
      significant increase in the number of micronuclei with beta-asarone, coumarin,
      monocrotaline and retrorsine could be detected in the presence of S9-mix and the
      cell line Hep-G2. Benzyl acetate, emodine, isatidine dihydrate, reserpine,
      safrole, sanguinarine chloride and thiourea did not reveal any micronucleus
      inducing activity in either human lymphocytes or in Hep-G2. In addition to the
      other Hep-G2 results in the literature, this human hepatoma cell line could have
      a useful potential in the in vitro micronucleus test.

PMID- 11299781
TI  - Topoisomerase I-DNA covalent complexes in human colorectal cancer xenografts with
      different p53 and microsatellite instability status: relation with their
      sensitivity to CTP-11.
AB  - The topoisomerase I poison CPT-11 has proved efficient for the treatment of
      untreated metastatic colorectal cancers (CRC) and those refractory to
      fluoropyrimidines. However, the interpatient variability is important. A previous
      in vitro study suggested that measurements of the level of topoisomerase I-DNA
      intermediates trapped by camptothecin may be useful to estimate the
      chemosensitivity of colon carcinoma cell lines. To verify this hypothesis, we
      developed an immuno-assay to detect covalent topoisomerase I-DNA complexes in a
      series of human colorectal cancers xenografted in nude mice. Six human CRCs were
      selected for their distinctive p53 and microsatellite instability (MSI) status.
      Tumour lysates, prepared from mice untreated or treated with CPT-11, were
      fractionated onto CsCl gradients to separate free and DNA-bound topoisomerase I
      by centrifugation. Interestingly, significant levels of DNA-topoisomerase I
      complexes were detected in the tumours most responsive to the treatment with CPT
      11, irrespective of their MSI and p53 phenotypes. Our in vivo study fully agrees
      with the predictions from the in vitro data indicating that evaluation of
      topoisomerase I-DNA complexes would be useful to predict the response of CRC to a
      treatment with CPT-11.

PMID- 11299782
TI  - Apoptosis-induction and phosphorylation state in human pancreatic carcinoma
      xenografts following octreotide treatment.
AB  - BACKGROUND: Some exocrine pancreatic carcinomas are responsive to hormonal
      manipulations, but the mechanism is not fully understood. MATERIALS AND METHODS:
      Human pancreatic cancer xenografts (PZX-15/F4) grown in immunosuppressed mice
      were treated with Sandostatin (2 x 100 micrograms/b.w. s.c.) for 4 weeks. Mitotic
      and apoptotic activities were assessed and supplemented with immunohistochemical
      detection of phosphotyrosine and bcl-2 protein. RESULTS: In the treated group
      5/16 tumors exhibited a 20-68% volume reduction, and the number of apoptotic
      cells was significantly increased (18.1 +/- 3.1/mm2 vs. 6.2 +/- 1.1/mm2 in
      controls, P < 0.0012). At the same time, a highly significant reduction in the
      number of the phosphotyrosine-positive tumor cells was observed (40.9% from
      64.9%; P < 0.0001). The mitotic activity did not change significantly. Both the
      untreated and the treated tumors proved to be bcl-2 negative. CONCLUSIONS: The
      results indicated that the octreotide triggered an apoptosis-induction in a human
      pancreatic cancer xenograft, coupled with the increased dephosphorylation state
      in the tumors, but the mitotic activity was not affected and bcl-2 expression has
      not been induced.

PMID- 11299783
TI  - Drug-resistant human laryngeal carcinoma cells have increased levels of cathepsin
      B.
AB  - In our previous work we showed that the drug-resistance of cervical carcinoma,
      laryngeal carcinoma and glioblastoma cells may be accompanied by increased levels
      of tumor markers for invasion and metastasis (i.e. urokinase-type plasminogen
      activator, plasminogen activator inhibitor type 1, and/or cathepsin D). In the
      present study we examined the concentration of cathepsins B, L and H in three
      drug-resistant clones isolated from human laryngeal carcinoma (HEp2). The basal
      levels of cathepsins B, L and H were determined by enzyme linked immunoabsorbent
      assay (ELISA). Our results showed that all three clones had an increased level of
      cathepsin B (in two clones an almost 4-fold increase was determined). The level
      of cathepsin L was altered (increased) only in VK2 clone, while the levels of
      cathepsin H were similar in parental cells and drug-resistant clones. Thus, our
      results suggest that drug-resistance may be accompanied by an increased level of
      cathepsin B, i.e. tumor associated protease, involved in invasion and metastasis.

PMID- 11299784
TI  - Time-dependent influence of procaine hydrochloride on cisplatin antitumor
      activity in P388 tumor bearing mice.
AB  - In previous papers (1,2) we demonstrated that procaine hydrochloride may increase
      the therapeutic index of cisplatin by an improvement of its antitumor activity
      and a reduction of its nephrotoxicity. In the present study we investigated the
      relationship between the antitumor activity obtained by cisplatin associated with
      procaine hydrochloride and the relative time of administration of these two
      agents. When procaine hydrochloride (40 mg/Kg body wt) was administered 30 or 120
      minutes before cisplatin (16 mg/kg) diluted in normal saline (i.e. clinical
      condition) it increased, although not significantly, its percent increase in life
      span (%ILS) and cure rate (%ILS: +292 and +217 vs +150; cure rate: 46.2% and
      42.3% vs 23%, respectively), compared to cisplatin alone treatment. These results
      became statistically significant when procaine hydrochloride was given either
      simultaneously with cisplatin or 30 and 120 minutes thereafter (%ILS: > 400 vs
      +150; cure rate: 65.4%, 73.1% and 68% vs 23%, respectively). In conclusion
      procaine hydrochloride increased the antitumor activity of cisplatin
      independently from its timing of administration, although it seemed to be a
      better potentiating agent when administered after cisplatin.

PMID- 11299785
TI  - Advanced colorectal cancer in elderly patients: tolerance and efficacy of
      leucovorin and fluorouracil bolus plus continuous infusion.
AB  - BACKGROUND: Colorectal cancer (CRC) incidence increases sharply with age. In this
      study we assessed activity, toxicity and both the activity of daily living (ADL)
      and instrumental activity of daily living (IADL) of the De Gramont schedule in a
      series of advanced CRC patients aged > or = 70 years. PATIENTS AND METHODS: Sixty
      two previously untreated advanced CRC patients entered the study. Median age was
      75 (range 70-88). RESULTS: 447 courses were delivered. All of the 62 patients
      were evaluable for toxicity, 55 for response and ADL-IADL indexes. We recorded 2
      complete and 9 partial responses, for an overall response rate of 20%. ADL and
      IADL indexes improved in 33%, remained stable in 49% and worsened in 18% of
      evaluable patients. Treatment was very well-tolerated with no serious
      hematological or non-hematological toxicities. CONCLUSIONS: The De Gramont
      schedule was very well tolerated in advanced CRC elderly patients, although our
      work could not confirm the original reported activity. ADL and IADL indexes
      improved or remained stable in 82% of evaluable patients.

PMID- 11299786
TI  - Alteration of nuclear matrix protein composition of neuroblastoma cells after
      arsenic trioxide treatment.
AB  - The aims of the present study were to assess the effects of arsenic trioxide on
      the nuclear matrix protein profiles of mouse neuroblastoma cells. Arsenic
      trioxide induces apoptosis of acute promyelocytic leukemia cells. Our results
      demonstrated that 2 microM As2O3 could significantly inhibit the growth of Neuro
      2a cells. As early as 24 hours after As2O3 treatment, we began to observe the
      alteration of nuclear matrix proteins and apoptosis in tumor cells by TUNEL assay
      but not by DNA ladder. An increase expression of Hsc in nuclear matrix proteins
      of 2 microM As2O3 treated cells was also noted. Our results also showed that
      before a mass range of apoptosis occurred, the composition of nuclear matrix
      proteins had altered. Hence the alteration of nuclear matrix proteins, such as
      increased expression of Hsc, may be a sensitive indicator for the detection of
      early apoptosis.

PMID- 11299787
TI  - Evidence that activation of MEK1,2/erk1,2 signal transduction pathway is
      necessary for calcitriol-induced differentiation of HL-60 cells.
AB  - Calcitriol (1,25-dihydroxyvitamin D3) induces differentiation and inhibits
      proliferation of human promyelocytic leukemia cells. The mechanisms involved in
      the regulation of these processes are not clearly understood. Previous studies
      have shown that calcitriol mediates cell differentiation not only by interaction
      with nuclear vitamin D receptor, but also by numerous rapid, membrane--mediated
      effects. Since in the light of past studies, involvement of raf/MEK1,2/erk1,2
      signal transduction pathway in calcitriol-induced cell differentiation was
      questionable, another attempt was undertaken in this study in order to
      investigate the problem. PD 98059, the specific inhibitor of MEK1 and MEK2 was
      found to inhibit calcitriol-induced monocytic differentiation of HL-60 cells.
      This finding proves that activation of the raf/MEK1,2/erk1,2 signal transduction
      pathway is essential for monocytic differentiation of human leukemia cells. The
      results reported in this paper suggest that inhibition of protein kinase C, which
      upstream regulates activation of erk1 and erk2, may be bypassed during the
      process of calcitriol-induced leukemia cell differentiation.

PMID- 11299788
TI  - Expression of laminin in metastatic melanoma cell lines with different metastatic
      potential.
AB  - Cancer metastasis is a complex multi-step process in which tumor cells leave the
      primary site and develop a secondary tumor in distant organs. Laminin plays an
      important role in this process. The expression of laminin in four melanoma cell
      lines with different metastatic potentials was investigated by
      immunohistochemistry, immunogold electron microscopy and Western blotting. Our
      results showed that the expression of endogenous laminin and the percentage of
      the positive cells are higher with increased metastatic potentials. It is, thus,
      suggested that endogenous laminin may contribute to the different metastatic
      properties in the melanoma cell line.

PMID- 11299789
TI  - DNA damage in buccal epithelial cells from individuals chronically exposed to
      arsenic via drinking water in Inner Mongolia, China.
AB  - The purpose of this pilot study was to assess DNA damage in buccal cells from
      individuals chronically exposed to arsenic via drinking water in Ba Men, Inner
      Mongolia. Buccal cells were collected from 19 Ba Men residents exposed to arsenic
      at 527.5 +/- 23.7 micrograms/L (mean +/- SEM) and 13 controls exposed to arsenic
      at 4.4 +/- 1.0 micrograms/L. DNA fragmentation by the DNA ladder and TUNEL assay
      were used to detect DNA damage in buccal cells. In the DNA ladder assay, 89%
      (17/19) of the arsenic-exposed group showed < 100 bp DNA fragments, in contrast
      to 15% (2/13) of the controls (p < 0.0001). For the TUNEL assay, the mean
      frequencies of positive cells were higher in the exposed group (15.1%) than in
      the controls (2.0%) (p < 0.0001). This study showed that high arsenic exposure
      via drinking water resulted in DNA damage and DNA fragmentation in buccal cells
      thus may be an appropriate biomarker for assessing chronic effects of arsenic in
      humans. A study investigating DNA fragmentation from the individuals with low
      levels of arsenic exposure in this population is in progress.

PMID- 11299791
TI  - Higher levels of soluble E-cadherin in cyst fluid from malignant ovarian tumours
      than in benign cysts.
AB  - A major diagnostic dilemma in the clinical gynaecological oncology setting is to
      preoperatively determine whether a complex ovarian mass is benign or malignant.
      The cell-cell adhesion molecule E-cadherin has previously been localised in
      biopsies from both benign and malignant epithelial ovarian tumours. In this
      study, soluble E-cadherin levels was measured with ELISA-technique in peripheral
      blood, ascites and cystic fluids from patients (n = 33) undergoing surgery for
      ovarian cystic masses. The levels of soluble E-cadherin were significantly higher
      in cystic fluid from cystadenocarcinomas (p < 0.001) and borderline tumours (p <
      0.05) as compared to cystic fluid from cystadenomas. In ascites fluid and
      peripheral blood no significant differences were seen. However, ratios of cystic
      fluid/peripheral blood levels were significantly higher in cystadenocarcinoma (p
      < 0.001) and borderline tumours (p < 0.05) as compared to benign tumours. In
      conclusion, measurements of soluble E-cadherin in cystic fluid from patients
      presenting with complex ovarian masses may be beneficial in increasing the
      accuracy of preoperative diagnosis.

PMID- 11299790
TI  - Tissue distribution and penetration of 5-ALA induced fluorescence in an
      amelanotic melanoma after topical application.
AB  - BACKGROUND: Photodynamic therapy (PDT) following topical application of 5
      aminolevulinic acid (ALA) is increasingly employed for several types of
      malignancies. However, data with respect to tissue penetration and distribution
      of ALA-induced porphyrins after topical application are scarce. Therefore, it was
      our aim to study tissue distribution and the penetration potency of topically
      applied ALA. MATERIAL AND METHODS: We used Syrian golden hamsters implanted with
      the amelanotic melanoma A-Mel-3 growing in a transparent dorsal skinfold chamber.
      ALA was topically applied in aqueous solution at a concentration of 3% for 4
      hours. The fluorescence pattern was quantified by fluorescence microscopy and
      digital image analysis from cryosections and given as percentage of a reference
      standard in medians (25%, 75% quartiles). RESULTS: Fluorescence intensities in
      tumors were 90.8% (56.2%, 115.2% of a reference standard, p < 0.01 vs. normal
      tissue) significantly exceeding normal surrounding host tissue yielding
      fluorescence intensities of 12.1% (9.1%, 16.1%). The tumor selectivity, that is
      the ratio of fluorescence intensities between tumor and normal tissue, was 7.3
      (6.1, 9.1). For superficial tumors with a thickness of approximately 1 mm no
      fluorescence gradients after topical application of ALA could be observed.
      CONCLUSION: In superficial cancerous lesions the fluorescence distribution of ALA
      induced porphyrins is tumor selective without significant fluorescence gradients
      throughout the tumor. Thus, by optimising the treatment modalities for topical
      ALA-PDT an enhanced efficacy and selectivity will be reached.

PMID- 11299792
TI  - Antiproliferative efficacy of the somatostatin analogue TT-232 in human melanoma
      cells and tumours.
AB  - BACKGROUND: TT-232, a somatostatin analogue, induces apoptosis in various
      tumours. The aim of our study was to characterise its effect on human melanoma
      cells and tumours. MATERIALS AND METHODS: Proliferation of seven melanoma cell
      lines was tested in vitro with the methylene blue test. D10 and 205 cells were
      also implanted into CB17-scid mice which received 30-150-750 micrograms/kg/day of
      TT-232 or saline. Animals with 205 cells received twice-daily subcutaneous
      injections whereas animals with D10 cells were treated with osmotic mini-pumps.
      In addition, TT-232 metabolites were generated with tissue homogenates and tested
      in vitro. RESULTS: TT-232 strongly inhibited proliferation of all cell lines in
      vitro and tumour growth in vivo. Two out of 8 animals (30-150 micrograms/kg) in
      the 205 model and one out of 8(150 micrograms/kg) in the D10 model became
      completely tumour-free at the 11th and 9th day of treatment, respectively. TT-232
      was degraded only by liver homogenate whilst its metabolite had no
      antiproliferative effect in vitro. CONCLUSIONS: TT-232 is a promising drug
      candidate for melanoma.

PMID- 11299793
TI  - The expression of basic fibroblast growth factor and vascular endothelial growth
      factor in prostatic adenocarcinoma: correlation with neovascularization.
AB  - BACKGROUND: Neovascularization associated with tumor invasion and metastasis may
      be stimulated by factors which are released from tumor cells, tumor-associated
      inflammatory cells or extracellular matrix. Although basic fibroblast growth
      factor (bFGF) and vascular endothelial growth factor (VEGF) have been
      characterized as promoters of angiogenesis, their precise localization in
      prostatic adenocarcinoma remains unclear. MATERIALS AND METHODS: In this study,
      the immunohistochemical expression of the growth factors and their receptors were
      studied using paraffin-embedded archival tissues before and after neoadjuvant
      hormonal therapy. The mRNA expression of the growth factors was also examined
      using an in situ hybridization (ISH) technique. RESULTS: The ISH study
      demonstrated that bFGF mRNA was present only in the stromal cells whilst that
      VEGF mRNA was present only in the adenocarcinoma cells. In contrast, the
      immunohistochemical study showed that bFGF, FGF receptor, VEGF and VEGF receptor
      proteins were expressed in adenocarcinoma cells and in endothelial cells. We also
      observed that microvessel density in prostatic adenocarcinoma was correlated with
      the degree of the expression of growth factors in the cases without neoadjuvant
      hormonal therapy. Additionally, the expression of those receptor proteins were
      much frequently identified in the cases with neoadjuvant hormonal therapy than
      those without it, while virtually no change in the expression of ligands was
      observed between the cases without and with neoadjuvant therapies. CONCLUSIONS:
      In prostatic adenocarcinoma, bFGF and VEGF may correlate with neovascularization
      through each characteristic pathway. In addition, we assumed that neoadjuvant
      hormonal therapy may have minimal inhibitory effects on bFGF, VEGF and their
      receptors.

PMID- 11299794
TI  - The cytogenetic view of standard comparative genomic hybridization (CGH):
      deletions of 20q in human leukemia as a measure of the sensitivity of the
      technique.
AB  - BACKGROUND: The limits of the resolving power of comparative genomic
      hybridization (CGH) have been given as 10-20 Mbp if at least 50% of the studied
      neoplastic cell population carried the corresponding aberration. MATERIAL AND
      METHODS: Genomic DNA of five cases of hematologic neoplasias, in all of which-
      among other anomalies--deletions of different size of chromosome 20q were found
      by GTG banding and confirmed by FISH analyses, was subjected to CGH. RESULTS: CGH
      revealed four types of del(20q), and, in addition, detected a tiny terminal
      del(3p) in one of the cases. The size of the smallest deleted segment, clearly
      visible by eye on the CGH metaphase image, was estimated to range between 5 and 7
      Mbp. CONCLUSION: Visual determination was shown to have a stronger resolving
      power in CGH than software used for the analysis in one case, while in another
      one, the results obtained from the ratio profiles would have been considered
      insignificant without the knowledge of the hybridization pattern on the
      corresponding CGH metaphase images. The potential of the standard CGH technique
      not only to detect, but visualize small segmental aneusomies as well, suggests
      that its resolution actually mirrors the resolution of banding techniques.

PMID- 11299795
TI  - Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro
      and relationship to tumour vascular targeting activity in vivo.
AB  - BACKGROUND: Combretastatin A4 Phosphate (CA4P) is a tubulin binding agent which
      causes rapid tumour vascular shutdown. It has anti-proliferative and apoptotic
      effects on dividing endothelial cells after prolonged exposure, but these effects
      occur on a much longer time scale than the reduction in tumour blood flow. This
      study compared the time course of CA4P effects on endothelial cell shape and
      reduction in red cell velocity. METHODS: Endothelial cell area and form factor (1
      4 pi x area x perimeter-2) were measured for proliferating and confluent HUVECs
      after CA4P treatment. Recovery of shape after CA4P and colchicine was compared.
      Window chamber studies of tumours were used to measure red cell velocity. Results
      70% reduction in red cell velocity and 44% reduction in HUVEC form factor
      occurred by 10 minutes. Proliferating HUVECs underwent greater cell shape change
      after CA4P, which occurred at lower doses than for confluent cells. Cell shape
      recovered 24 hours after 30 minutes exposure to CA4P, but not after colchicine.
      CONCLUSIONS: The similar time course of cell shape change and red cell velocity
      reduction suggests endothelial cell shape change may be involved early in the in
      vivo events leading to vascular shutdown. Differences in the recovery from the
      shape changes induced by CA4P and colchicine could underlie the different
      toxicity profiles of these drugs.

PMID- 11299796
TI  - Laminin-5 as a predictor of invasiveness in cancer in situ lesions of the larynx.
AB  - Squamous epithelial cancer in situ (CIS) of the upper aerodigestive tract is a
      histopathologically well-defined condition. There is yet no reliable way to
      predict whether a CIS lesion will progress to invasive cancer, remain stable or
      regress. In the search for markers able to foretell clinical outcome, we
      performed immunohistochemical staining with a polyclonal antibody against
      recombinant gamma 2 chain of laminin-5 in 33 laryngeal CIS lesions. All six CIS
      lesions which progressed to invasive cancer, within a follow-up time of 5 years,
      were laminin-5 positive (100%), whereas only 10 out of 27 lesions which did not
      progress were positive (37%) (p < 0.01). Our data showed that a positive laminin
      5 laryngeal CIS lesion indicates a high risk for progression to invasive cancer.

PMID- 11299797
TI  - Mutations of p53 gene in gastric carcinoma in Taiwan.
AB  - BACKGROUND: p53 gene mutation and p53 protein accumulation is the most common
      event in human cancers. The present study was conducted to investigate the
      occurrence of p53 mutations in patients with gastric carcinoma in Taiwan.
      MATERIALS AND METHODS: Tumor samples from 36 patients with primary gastric
      carcinoma undergoing radical gastrectomy were evaluated. The mutational status of
      the p53 (exons 5 to 8) was screened by polymerase chain reaction/single strand
      conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing.
      These results were compared with p53 protein expression as assessed by
      immunohistochemical staining. RESULTS: Of all 36 gastric carcinomas, mutations of
      the p53 gene were found in 7 cases (19.4%). These results from direct sequencing
      indicated that mutations consisted of five missence mutations, one silent
      mutation and one mutation within the splice donor site of intron 5. Mutations
      were found at codon 145 in exon 5 (1 case), intron 5 (1 case), codon 248 in exon
      7 (1 case), codon 251 in exon 7 (2 cases), codon 285 in exon 8 (1 case) and codon
      287 in exon 8 (1 case). The mutation hot spot at codon 251 in gastric cancer has
      not been observed previously. Over-expression of p53 oncoprotein was observed in
      10 patients (27.8%) immunohistochemically. CONCLUSIONS: p53 gene mutation might
      contribute to the pathogenesis of human gastric carcinoma. However, the
      suggestion awaits further investigation for confirmation.

PMID- 11299798
TI  - p53, p21 and p27 protein expression in head and neck cancer and their prognostic
      value.
AB  - Histological specimens from 62 laryngeal and 31 oral carcinomas were
      immunohistochemically assessed for p53, p21 and p27 proteins; cases with > 10%
      labelled nuclei were considered as positive. p21 showed higher expression in
      patients > 65-years-old (P = 0.04), in chemotherapy responders (P = 0.02), and in
      stage III patients with longer overall survival (P = 0.02), representing the only
      independent prognostic factor in the multivariate analysis. In addition, stage
      III patients with p53-/p21+ showed the longest survival whereas those with
      p53+/p21- tumors showed the shortest overall survival (P = 0.02). A significant
      influence on the survival of stage III patients was also found for the
      combinations of p21 and p27 proteins with p21+/p27- imparting the best and p21
      /p27+ the worst prognosis (P = 0.04). p27 expression was significantly related to
      oral cancer specimens (P = 0.04) and to moderate and high tumor grade (P = 0.01).
      p53 expression was not significantly related to any of the examined
      clinicopathological characteristics. Our findings indicated that, by functionally
      promoting apoptosis, p21 seems to play a key role in the successful response to
      chemotherapy and may be considered as a predictive factor of a better prognosis
      in stage III patients with head and neck cancers.

PMID- 11299799
TI  - Human papilloma virus (HPV) and p53 immunostaining in advanced tonsillar
      carcinoma--relation to radiotherapy response and survival.
AB  - BACKGROUND: Human papilloma virus (HPV), which is frequently present in tonsillar
      carcinoma seems to be a prognostically favourable factor for patient survival and
      also for low risk of relapse. Since HPV may abrogate the function of wild type
      p53 and hence influence radiosensitivity we attempted to analyse if HPV and p53
      status in tonsillar carcinoma affected tumour response to radiotherapy (RT) and
      patient survival. MATERIALS AND METHODS: Pre-treatment primary tonsillar
      carcinoma specimens were obtained retrospectively from 40 patients, 21 complete
      responders (CR) and 19 non-complete responders (non-CR) of which 38/40 were stage
      III and IV tumours. The paraffin-embedded biopsies were analysed for presence of
      HPV DNA, by general and type specific PCR, and for p53 overexpression by
      immunohistochemical staining with the murine Mab DO-1. RESULTS: It was possible
      to analyse HPV in 34 and p53 in 39 patients. Presence of HPV DNA (HPV+) and p53
      immunostaining (p53+) were not correlated with response to RT, since 8/18 CR
      patients and 6/16 non-CR patients were HPV+ and 11/21 CR patients and 8/18 non-CR
      patients were p53+. A tendency towards a survival benefit in patients with HPV+
      tumours was observed and this tendency was significant for patients with stage IV
      HPV + tumours (p = .0431), and in particular HPV+/p53- cancers (p = .0195). A
      difference in survival between patients with p53+ cancer as compared to patients
      with p53- lesions was not demonstrated. In conclusion, although presence of HPV
      and p53 immunoreactivity in tonsillar carcinoma could not be related to RT
      response, determination of HPV and p53 status may still prove useful as
      predictive/prognostic markers.

PMID- 11299800
TI  - Reduced HIC-1 gene expression in non-small cell lung cancer and its clinical
      significance.
AB  - BACKGROUND: HIC-1 (hypermethylated in cancer-1) is a candidate tumor suppressor
      gene, identified in a region of frequent loss of heterozygosity on chromosome
      17p13.3, which is telomeric from TP53 and often deleted in surgically resected
      lung cancers. To determine the significance of HIC-1 in lung cancer, we assessed
      its expression status and prognostic association in 47 adenocarcinomas and
      squamous cell carcinomas. MATERIALS AND METHODS: RNA was extracted from tumors
      and corresponding normal tissues of surgically resected lungs, and the amount of
      HIC-1 mRNA was determined by means of semi-quantitative reverse transcriptase
      polymerase chain reaction. RESULTS: HIC-1 expression in tumors was less than that
      in normal lung tissues in 40 of 47 patients (85%), indicating frequent partial
      silencing. Median tumor/normal lung tissue (T/L) ratios for HIC-1 expression were
      0.51 and 0.75 for adenocarcinomas and squamous cell carcinomas, respectively. No
      significant difference of median T/L ratio was observed between the two
      histological types, or among clinical stages of the patients. However, the
      reduced expression of HIC-1 gene in the tumor had a direct link with the clinical
      outcome: lower T/L ratios (< 0.5) were significantly associated with short
      survival (P = 0.034), an association also observed in cases restricted to stage I
      (P = 0.047). CONCLUSIONS: The results suggest that low HIC-1 expression is
      involved in malignant progression of non-small cell lung cancer.

PMID- 11299801
TI  - Expression of transferrin receptor and ferritin H-chain mRNA are associated with
      clinical and histopathological prognostic indicators in breast cancer.
AB  - It is well known that iron plays an essential role in many biochemical reactions
      and that rapidly growing cells require more iron for their growth and metabolism
      than resting cells. Transferrin and its receptor are required for entry of iron
      into the cell. In contrast, ferritin is a cellular storage protein whose main
      function is to sequester excess ferric iron and thus prevent high concentrations
      of soluble ferric iron from becoming toxic to the cell. However, the clinical
      significance of both transferrin receptor and ferritin mRNA levels have not
      previously been described in tumors from breast cancer patients. In this study,
      tumor tissue mRNA levels of transferrin receptor and ferritin were quantitated on
      forty-two breast cancer patients. A highly sensitive non-radioisotopic cDNA
      polymerase chain reaction assay was used to quantitate expression of mRNA. The
      expression of glyceraldehyde-3-phosphate dehydrogenase served as the control. In
      the tumor tissue from the 42 breast cancer patients the transferrin receptor mRNA
      levels were significantly correlated to the ferritin H-chain mRNA levels
      (Spearman correlation r = 0.5433, p = 0.0002; Pearson correlation r = 0.6276, p <
      0.0001). The level of amplified transferrin receptor complementary DNA was
      related to differentiation (ANOVA, p = 0.042) with poorly differentiated tumors
      having high levels of transferrin receptor mRNA. Further, the levels of amplified
      gene for ferritin heavy chain complementary DNA was directly related to axillary
      lymph nodes status (Student's t-test, p = 0.044), presence of metastatic disease
      (Student's t-test, p = 0.046) and clinical stage (stage I + stage II versus stage
      III + stage IV; Student's t-test, p = 0.0181). These results demonstrate that non
      radioisotopic RT-PCR is a very sensitive method for determining mRNA levels in
      tumor tissue. Additionally, the quantitation of expression of transferrin
      receptor and ferritin heavy chain mRNA may be useful for assessing prognosis and
      guiding therapeutic decisions in breast cancer patients.

PMID- 11299802
TI  - Levels of alpha 2 macroglobulin can predict bone metastases in prostate cancer.
AB  - BACKGROUND: In prostate cancer, we previously reported that a marked decrease of
      serum alpha 2 macroglobulin (alpha 2M) to less than approximately 50 mg/dl was
      associated with the presence of bone metastases. In order to investigate the
      relationship between bone metastases and alpha 2M, we assessed these two
      parameters in 128 patients with prostatic diseases. MATERIALS AND METHODS: 66
      patients with untreated benign prostatic hypertrophy and 62 with untreated
      prostate cancer were included in the study. Measurement of alpha 2M concentration
      was performed by Laser-Nephelometry, prostate-specific antigen (PSA) by EIA.
      RESULTS: The serum alpha 2M levels in prostate cancer with bone metastases showed
      a significantly lower level compared with the group without bone metastases (p <
      0.01). Cases with serum alpha 2M levels of less than 50 mg/dl all had bone
      metastases. Serum alpha 2M levels were inversely related to PSA levels in stage
      M1b disease. CONCLUSIONS: Measurement of serum alpha 2M levels may be useful for
      the diagnosis and follow up of bone metastases in prostate cancer.

PMID- 11299803
TI  - Evaluation of total PSA assay on vitros ECi and correlation with Kryptor-PSA
      assay.
AB  - BACKGROUND: An increasing number of multiparametric immuno-analysers for PSA
      assays are available. As different immuno-assays may vary in their analytical
      quality and their accuracy for the follow-up of patients, expertise is necessary
      for each new assay. METHODS: The PSA assay on the Vitros-ECi analyser has been
      evaluated and compared with the PSA assay from the Kryptor analyser. RESULTS:
      Variation coefficients were 0.91 to 1.98% for within-run assays, and 4.2% to 5.4%
      for interassay (PSA levels = 0.8 microgram/L to 33.6 micrograms/L). Dilution
      tests showed 93 to 136% recovery until 70 micrograms/L PSA. Functional
      sensitivity was estimated at 0.03 microgram/L. Equimolarity of the test was
      confirmed. Correlation of PSA levels measured with Vitros-ECi and Kryptor
      analysers displayed a correlation coefficient r2 of 0.9716. The half-lives and
      doubling times of PSA were similar using both methods. CONCLUSION: Vitros-ECi PSA
      assay meets the major criteria for the management of prostate cancer patients.

PMID- 11299804
TI  - Malignant bronchial Abrikossoff's tumor and small cell lung cancer: a case report
      and review.
AB  - A 61-year-old male Caucasian smoker patient underwent chest radiography and CT
      scan for persistent non-inflammatory cough, which showed a left bronchial
      unresectable mass. Bronchoscopy showed an endobronchial mass; washing cytology
      was negative and histology findings suggested diagnosis of granular cell tumor
      (GCT), also called Abrikossoff's tumor. After 3 weeks a new washing cytology test
      revealed the presence of small cell lung cancer (SCLC). A CT-scan and chest
      radiography showed a 30% increase in the maximum diameter of the lesion,
      clinically defining the primary neoplasm as malignant. The patient was referred
      to our institution and started chemotherapy with cisplatin and etoposide. After 6
      cycles of treatment, the CT scan showed complete, disappearance of the neoplasm
      and bronchoscopy examination showed no endobronchial lesion, defining the mucosal
      surface as normal. We have reviewed and summarized the international literature
      with regard to bronchial localization of malignant granular cell tumor and its
      association with SCLC, therefore concluding that our case is the first malignant
      endobronchial GCT linked to SCLC.

PMID- 11299805
TI  - Collecting duct carcinoma mixed with common renal cell carcinoma: analysis of
      morphological characteristics using lectin histochemistry.
AB  - Recently, cases of collecting duct carcinoma have been reported which were
      thought to have arisen from the renal collecting ducts or distal tubuli. We
      present here a rare case of collecting duct carcinoma mixed with common
      (conventional) renal cell carcinoma. A 51-year-old man underwent right
      nephrectomy under the diagnosis of renal tumor. Histochemically, markers for the
      collecting ducts/distal tubuli, such as peanut agglutinin (PNA) and soybean
      agglutinin (SBA), were identified in the collecting duct carcinoma as well as on
      several luminar surfaces of the common renal cell carcinoma. Based on the results
      of histological, histochemical and chromosomal examinations, we speculated on the
      histogenesis of this collecting duct carcinoma.

PMID- 11299807
TI  - Glut 1 expression in transitional cell carcinoma of the urinary bladder is
      associated with poor patient survival.
AB  - Cancer cells show increased glucose uptake compared to normal cells. Glut1 has
      been shown to be expressed in many human cancers, including transitional cell
      carcinoma of the urinary bladder (TCCB). The aim of this study was to determine
      the biologic significance of Glut1 expression, as determined by
      immunohistochemistry, in TCCB. Using the polyclonal anti-Glut1 antibody MYM,
      microwave-aided antigen retrieval, and standard immunoperoxidase ABC technique,
      we immunostained sections of formalin-fixed and paraffin-embedded tissue from
      cystectomy specimens from 40 patients with TCCB, who received no adjuvant
      therapy. The percent of positive cancer cells was scored on a semiquantitative
      scale as 1) 0%, 2) 1-10%, 3) 11-25%, 4) 26-50%, 5) 5.1-75%, and 6) > 75%.
      Statistical analysis was performed using the Kaplan-Meier survival method, the
      Log rank test, and Fisher's exact test. Glut1 immunoreactivity was detected in
      58% of the cases. Glut1 expression in > 10% of cancer cells was associated with
      worse patient survival than expression in < 10% of the cancer cells (p = 0.0064).
      Tumors with > 10% Glut1-positive cancer cells were more likely to be of pT2 stage
      or higher than tumors with < 10% Glut1-positive cells (100% vs 68%, respectively,
      p = 0.0109), but showed no significant difference in the incidence of nodal
      metastasis (p = 0.4258). Our results suggest that Glut1 expression in TCCB is a
      marker of aggressive biologic potential in patients undergoing cystectomy.

PMID- 11299806
TI  - Treatment of classical type Kaposi's sarcoma with paclitaxel.
AB  - Paclitaxel has recently been shown to be effective in treating acquired
      immunodeficiency syndrome-associated Kaposi's sarcoma. We report good therapeutic
      effects of paclitaxel in two patients with classical form Kaposi's sarcoma (KS)
      which had poor or partial response to chemotherapy (vincristine, vinblastine,
      oncovin, bleomycin, epirubicin, dactinomycin, decarbazine) and interferon alpha
      2b. Paclitaxel appears to be active against Kaposi's sarcoma as a single agent.
      The experience suggests that paclitaxel is an effective alternative in the
      treatment of classical form Kaposi's sarcoma.

PMID- 11299808
TI  - Evaluation of genital human papillomavirus infections by polymerase chain
      reaction among Croatian women.
AB  - Infection with specific human papillomavirus (HPV) types is the strongest risk
      factor in cervical carcinogenesis. In this study we analysed, by means of
      polymerase chain reaction (PCR), cervical specimens obtained from consenting
      women with abnormal Pap smears collected from 1996 to 1998. Consensus- and type
      specific-primers directed PCR were used in order to detect the presence and to
      determine the most common HPV types: 6, 11, 16, 18, 31 and 33. Out of 1874
      specimens, 1207 (64%) contained one or more HPV types. Approximately half HPVs
      were typed (621 out of 1207) and the others remained untyped (586 out of 1207),
      51% and 49%, respectively. Beside low-risk HPV 6/11 (5%), the most frequently
      observed HPVs were high-risk HPV types, especially type 16 (12%), while HPV types
      18 (2%), 31 (5%) and 33 (3%) were less frequent. The HPV positivity rate declined
      with age, although all HPV types were equally distributed in different age
      groups. The presence of HPV DNA significantly increased from 55% to 78% along
      with the severity of the cervical lesions, i.e. low- and high-grade squamous
      intraepithelial lesions (LSIL, HSIL). Undetermined HPV types, other than 6/11,
      16, 18, 31 and 33 were equally distributed in LSIL and HSIL which indicates that
      they represent low- as well as high-risk HPV types. Our results indicated that
      HPV infections, especially those with HPV 16, represent a significant public
      health concern in Croatia.

PMID- 11299809
TI  - Effect of tamoxifen on GH and IGF-1 serum level in stage I-II breast cancer
      patients.
AB  - OBJECTIVE: Tamoxifen suppresses insulin-like growth factor-1 (IGF-1) plasma
      levels in early and advanced breast cancer patients. Relationships between
      tamoxifen (GH) and IGF-1 are complex and not completely described yet. The
      present investigation was performed to evaluate the effect of acute and chronic
      tamoxifen administration on GH response to growth hormone-releasing hormone
      (GHRH), as well as on IGF-1 serum levels. MATERIALS AND METHODS: Evaluation of GH
      after administration of GHRH was performed (a) at baseline, (b) 3 hours after 20
      mg oral administration of tamoxifen and (c) after 12 weeks of 20 mg a day oral
      tamoxifen treatment, in fifteen postmenopausal stage I-II breast cancer patients.
      IGF-I was measured at baseline and after chronic tamoxifen administration.
      RESULTS: The GH response to GHRH was significantly reduced after 12 weeks of
      tamoxifen 10 mg administered twice a day orally (mean peak 3.2 +/- 0.2
      micrograms/l, mean AUC 261.3 +/- 18.2 micrograms/minute p < 0.01 versus basal
      AUC). A concomitant significant reduction of IGF-1 was observed after 3 months of
      tamoxifen treatment. Basal pretreatment levels of 113.2 +/- 15.5 micrograms/l
      were suppressed to 70 +/- 7.9 micrograms/l (p < 0.01). CONCLUSION: Our study
      confirm the inhibitory effect of tamoxifen on IGF-I and suggested, as shown in
      previous in vitro data, that its suppression could be directly related to GH
      reduction in response to GHRH stimulation.

PMID- 11299810
TI  - Re-evaluation of prognostic mitotic figure counting in breast cancer: results of
      a prospective clinical follow-up study.
AB  - Some years ago we were able to confirm reports on the prognostic meaning of
      mitotic figure counting in breast cancer on a retrospective series of 104 breast
      cancer cases (Hum Pathol 26: 47-52, 1995). An independent influence of mitotic
      figure counting on prognosis could be proven in stage I and stage II tumors.
      Using the same methodological approach, the investigation has been repeated
      recently on a prospectively collected series of breast cancer patients (n = 108).
      A strong benefit for the patients' outcome was found for patients with stage II
      tumors (p = 0.0093), but not for patients with stage I tumors (p > 0.05).
      Regarding the differences between the two studies, most probably the effects of
      therapeutic changes between the late 1970s and the late 1980s and aspects of the
      patients' selection may be responsible.

PMID- 11299812
TI  - Hematopoietic progenitor cell counts performed by the Sysmex SE-9000 analyzer can
      guide timing of peripheral blood stem cell harvest.
AB  - BACKGROUND: We studied whether the hematopoietic progenitor cell (HPC) count in
      peripheral blood as evaluated by an automated counter, the Sysmex SE-9000,
      correlated with CD34 positive (+) cell count and therefore could guide the timing
      of peripheral blood stem cell (PBSC) harvest. MATERIALS AND METHODS: HPC count
      and flow cytometric CD34+ cell count were measured in 90 peripheral blood samples
      and 30PBSC samples. The correlation between HPC count and apheretic CD34+ cell
      yield was examined in 19 patients. RESULTS: HPC count showed good correlations
      with CD34+ cell count in peripheral blood (r = 0.699) and PBSC (r = 0.892). The
      correlation between peripheral blood HPC count and apheretic CD34+ cell yield
      also was good (r = 0.789). CONCLUSION: Automated HPC counting can be used as a
      screening test to guide the timing of PBSC harvest.

PMID- 11299811
TI  - Quantitative analysis of the anti-apoptotic gene survivin expression in malignant
      haematopoietic cells.
AB  - BACKGROUND: In this study we investigated expression profiles of the anti
      apoptotic gene survivin in malignant human haematopoietic cells. MATERIALS AND
      METHODS: Using a quantitative TaqMan reverse transcription-polymerase chain
      reaction, survivin and bcl-2 mRNA expression were examined in 12 malignant
      haematopoietic cell lines, in 21 patients with haematopoietic malignancies and in
      normal leukocyte fractions. RESULTS: Survivin mRNA levels, demonstrable in all 12
      malignant cell lines, differed but showed no relationship to the cell of origin.
      Conversely, no survivin mRNA expression was detected in normal leukocyte
      fractions. Further, survivin mRNA was expressed in 16 out of 21 patients with
      malignancies. Five days after treatment of HL-60 cells with a combination of all
      trans retinoic acid and tumor necrosis factor, survivin expression decreased to
      14.1% of that in untreated cells. Further, survivin mRNA expression in K-562/ADR
      cells with acquired resistance to adriamycin was 1.7 times that in parent K-562
      cells. CONCLUSION: Our results indicated the possibility that quantitation of
      survivin mRNA expression is a useful tool for the detection of haematopoietic
      tumor cells in clinical laboratory test and that survivin could be a target for
      treatment of haematopoietic malignancies.

PMID- 11299813
TI  - Rater agreement and utility of the mutagen-induced chromosome damage assay.
AB  - Chromosomal damage in peripheral blood lymphocytes induced by short-term in vitro
      exposure to the cytotoxic antibiotic bleomycin was first described in 1983 and
      proposed as a phenotypic assay for chromosome instability. This assay was
      subsequently described as potentially useful in assessing an individual's risk to
      environmental carcinogens in 1989. Since 1995 numerous published studies have
      used this assay to assess risk for cancer in the aerodigestive tract,
      particularly lung cancer, in various ethnic populations. Odds ratios up to 8.5
      have been reported for individuals deemed "mutagen sensitive" (defined as > or =
      1 chromatid break per metaphase averaged in 50 metaphases analyzed). While this
      phenotypic assay is appealing for lung cancer risk assessment it has not been
      reproduced by other investigators. Because of our interest in lung cancer
      biology, epidemiology, and genetics, we sought to independently assess the rater
      agreement of this assay. We found that 1) the assay is laborious to conduct (8
      hours of labor) and relatively expensive (> $100), yet reducing the number of
      metaphases from 50 to 20 produced a reliable, less expensive, and less laborious
      test; and 2) the rater agreement of individual metaphase readings is poor, but
      agreement for a summary measure is high.

PMID- 11299814
TI  - Prognostic status of p53 gene mutation in canine mammary carcinoma.
AB  - BACKGROUND: The p53 gene mutations have been associated with the development of
      human breast and canine mammary neoplasms; breast carcinoma patients with
      alterations of p53 gene are considered to have a poor prognosis. Mammary
      carcinoma represents the most common malignant tumor in female dogs. However, the
      prognostic significance of p53 gene mutation in the dog has been unclear. STUDY
      DESIGN: The alteration in exons 5-8 of p53 gene in 69 canine mammary carcinomas
      were investigated by PCR-SSCP with direct sequence analysis and statistically
      analyzed to compare with other clinicopathological parameters including age,
      neuter, tumor size, stage, histology, p53 expression, recurrence and death from
      carcinoma. RESULTS: 12 out of 69 (17%) carcinomas showed p53 gene mutations.
      After a follow-up period of 30 months, multivariate regression analysis revealed
      that p53 gene mutation was only an independent risk factor for increased risk of
      the recurrence and death from mammary carcinoma. CONCLUSION: The p53 gene
      alterations might contribute to the prognostic status in canine mammary
      carcinomas, in a way comparable to that of human tumors.

PMID- 11299815
TI  - Histological grading in gastric cancer by Goseki classification: correlation with
      histopathological subtypes and prognosis.
AB  - BACKGROUND: Many different classification systems have been proposed for the
      histological classification and grading of gastric cancer. In 1992 Goseki
      described a novel classification system for gastric cancer based on tubular
      differentiation and mucus in the cytoplasm. The aim of the study was to compare
      the Goseki classification with the currently used classification systems and to
      define the prognostic significance of the Goseki classification system. PATIENTS
      AND METHODS: The present study analyzed material from 200 gastric carcinoma
      patients who underwent gastrectomy with curative intention. All specimens were
      categorized to UICC-classification, WHO-classification, Lauren classification,
      tumor differentiation and Goseki classification. The median follow-up for
      surviving patients was 3.75 years (range, 0.14-11.52). RESULTS: According to the
      Goseki classification 32% of patients were classified as group I, 11.5% as group
      II, 9.5% as group III and 48% as group IV. The Goseki classification was found to
      correlate with the WHO and Lauren classification as well as with conventional
      grading. Goseki classification as well as tumor differentiation, Lauren and WHO
      classification did not have prognostic value for survival. Only the UICC system
      presented as an independent prognostic factor in multivariate analysis (p <
      0.000001). CONCLUSION: In our series Goseki classification correlated with
      conventional classification systems, but not with survival.

PMID- 11299817
TI  - Serum ceruloplasmin in melanoma patients.
AB  - We have studied the serum ceruloplasmin levels as a possible diagnostic factor or
      marker for detection, diagnosis and follow-up of patients with melanoma.
      Ceruloplasmin concentration was determined in 64 melanoma patients (MP) and in 37
      healthy persons (HP) by nephelometry. We found a mean value of 29.85 +/- 5.47
      mg/dl in MP and 26.10 +/- 5.22 mg/dl in HP. A significant increase in the levels
      of serum ceruloplasmin was observed in MP in comparison to those in HP (P =
      0.0011). In order to check whether this test could discriminate between MP and
      HP, a complete statistical Receiver Operating Characteristic (ROC) curve analysis
      was performed. The cut-off value was 25.10 mg/dl. The area under the curve was
      0.689. According to these results, the test could discriminate adequately between
      the two groups.

PMID- 11299816
TI  - Immunotherapy for recurrent colorectal cancers with human monoclonal antibody SK
      1.
AB  - BACKGROUND: The human monoclonal antibody SK-1 recognizes a glycoprotein
      expressed on the majority of colon cancer tissues. In the current study, we
      evaluated the safety, toxicity and preliminary efficacy of escalating dosages of
      SK-1 in patients with advanced colon cancer. PATIENTS AND METHODS: SK-1 was
      administered intravenously at 2, 4 or 10 mg three times to three groups of
      patients with recurrent colon cancer. The clinical outcome and the induction of
      serum anti-idiotypic antibody (Ab2) were assessed periodically. RESULTS: The mean
      rate of serum CEA level increase declined significantly during the eight weeks
      following the treatment. In four patients, serum titer of anti-idiotypic IgG
      antibodies to SK-1 (Ab2) continued to increase following the treatment.
      CONCLUSION: HuMAb SK-1 was well-tolerated and can be safely administered. It was
      suggested that SK-1 natural antibody not only possessed direct cytostatic
      activity against colon carcinoma, but may also have induced carcinoma-related,
      anti-idiotypic antibody responses.

PMID- 11299818
TI  - Quantitation of multiple myeloma oncogene 1/interferon-regulatory factor 4 gene
      expression in malignant B-cell proliferations and normal leukocytes.
AB  - BACKGROUND: We studied multiple myeloma oncogene 1/interferon-regulatory factor 4
      (MUM1/IRF4) mRNA expression in various malignant human hematopoietic cell lines
      and normal leukocyte fractions. MATERIALS AND METHODS: A quantitative reverse
      transcription-polymerase chain reaction was used to assess expression and
      chromosomes were examined for anomalies by fluorescent in situ hybridization.
      RESULTS: Among 12 cell lines examined, mRNA transcripts were expressed only in B
      lymphoblastic and myeloma cell lines. Myeloma cells and malignant cell lines
      derived from mature B cells expressed more transcript than cell lines derived
      from immature B cells. Transcript levels, however, showed no association with
      chromosomal translocations. Expression in B-cell fractions from healthy donors
      was much less than in the malignant cells. In addition, MUM1/IRF4 mRNA expressed
      in samples from patients with acute lymphoblastic leukemia derived from B cells
      but not T cells. CONCLUSION: Our results suggested that MUM1/IRF4 gene expression
      is related to stage of differentiation of malignant B cells and they indicated
      the possibility that the quantitative analysis of MUM1/IRF4 gene is a useful tool
      for detection of malignant B-cell proliferations in clinical laboratory tests.

PMID- 11299819
TI  - Overexpression of placental tissue protein 17b/TIP47 in cervical dysplasias and
      cervical carcinoma.
AB  - In our previous Western- and Northern-blot investigations, high over-expression
      of placental protein 17b/TIP47 was detected in extracts of human cervical
      carcinoma tissues compared to normal conditions of the cervical tissue. PP17b
      serum levels were also elevated in untreated cervical carcinoma patients compared
      to healthy controls. In the present study, the expression pattern of PP17
      proteins was investigated in various cervical dysplasias and in cervical
      carcinoma tissue specimens by the streptavidin-biotin immunoperoxidase technique
      using PP17-specific antiserum. In normal third-trimester human placentas, which
      served as positive controls, mainly cytoplasmic PP17 immunostaining of
      syncytiotrophoblasts and chorionic trophoblasts was observed. Normal human
      uterine cervical squamous and glandular epithelia were negative or weakly
      positive, while in low grade dysplasias (CIN I-II) only the cytoplasms of
      dysplastic cells were weakly positive or positive; in high grade dysplasias (CIN
      III/ISC) cytoplasms of the dysplastic cells were strongly positive. Normal and
      superficial cells in the differentiated zones were negative in all tissue
      specimens. In cases of invasive epithelial cervical carcinomas, small basal-type
      tumour cells were mostly negative whilst cells with squamous differentiation were
      strongly positive for PP17. Our hypotheses for this newly detected phenomenon are
      briefly discussed.

PMID- 11299820
TI  - Vascular integrin beta 3 and its relation to pulmonary metastasis of colorectal
      carcinoma.
AB  - Integrin alpha v-beta 3 is involved in tumor angiogenesis while the clinical
      significance of beta 3 integrin expression in colorectal cancer and lung
      metastases. Analysis was performed on 51 colorectal cancer patients (22 with
      subsequent lung metastasis and 29 without lung metastasis). Fifty-one primary
      tumors and 22 lung metastases were examined for immunohistochemical detection of
      integrin beta 3. We found that the antibody VNR 5 to integrin beta 3 prefentially
      stains the blood vessels of small caliber. Indeed, vascular integrin beta 3 index
      was significantly higher in tumors of patients with lung metastasis than in those
      without lung metastasis. In the patients with lung metastases, vascular integrin
      beta 3 index was significantly lower in lung metastases than in primary tumors.
      It was immunohistochemically proved that integrin beta 3 is an important vascular
      endothelial cell market for lung metastasis.

PMID- 11299821
TI  - Elevation of serum alkaline phosphatase in clear cell chondrosarcoma of bone.
AB  - BACKGROUND: Clear cell chondrosarcoma is a rare bone tumor, which is sometimes
      misdiagnosed as a different bone neoplasm. MATERIALS AND METHODS: The files of 6
      patients with clear cell chondrosarcomas were reviewed. Histological slides,
      radiographic studies, and pre- and post-operative serum alkaline phosphatase
      (ALP) levels were evaluated. Molecular and histochemical analyses of ALP were
      documented in one case of clear cell chondrosarcoma. RESULTS: Pre-operative serum
      ALP levels were elevated in 3 patients, and were normal in another 3 patients.
      After removal of the tumors, the enzyme levels decreased in all patients and
      returned to normal in 3 patients, who had pre-operative high ALP levels. Enzyme
      histochemical and molecular analyses demonstrated that the tumor produced ALP.
      CONCLUSION: Clear cell chondrosarcoma produces ALP, which can be used as a tumor
      marker in diagnosis and follow-up.

PMID- 11299822
TI  - Enhanced expression of cyclin E and cyclin A in human hepatocellular carcinomas.
AB  - BACKGROUND: Disruption of the G1/S check point leads to uncontrolled cell growth,
      resulting in the development of cancers. MATERIALS AND METHODS: Cell cycle
      regulatory molecules were investigated in 33 surgically resected hepatocellular
      carcinoma (HCC) samples from 30 patients by Western blotting. RESULTS: Enhanced
      expressions of cyclin E and cyclin A were detected at frequencies of 18/33 and
      26/33 in HCCs, respectively, as compared with their neighboring noncancerous
      tissues. The enhanced expression of cyclin E, but not that of cyclin A,
      correlated with hyperphosphorylation of pRb and high frequency of Ki-67-positive
      cells. Thus, the HCCs with enhanced cyclin E expression probably contain a
      relatively large number of proliferating cancer cells. CONCLUSIONS: The degree of
      cyclin E expression can be used as a prognostic parameter of HCC. In addition,
      cyclin E may become a molecular target in the treatment of HCCs.

PMID- 11299823
TI  - Clinical and experimental evidence of Bcl-2 involvement in the response to
      photodynamic therapy.
AB  - PURPOSE: The role of apoptosis related proteins in the response of human
      malignancies to photodynamic therapy (PDT) is under investigation. The aim of the
      study was to examine the role of p53 and of bcl-2 protein expression in the
      response to PDT. MATERIALS AND METHODS: Paraffin-embedded material from 37
      patients with early esophageal cancer treated with PDT (argon dye laser after
      intravenous injection of hematoporphyrine derivative) was studied
      immunohistochemically for p53 protein nuclear accumulation and bcl-2 cytoplasmic
      expression. Patients with residual disease after two rounds of PDT received
      definitive radiotherapy. In a subsequent in vitro study, W138 human lung
      fibroblasts and W138-SV-40 virus transformed were assessed for their sensitivity
      to PDT. The constitutive bcl-2 overexpression of the transformed cells vs. normal
      cells (assessed with RT-PCR) was 16-fold. RESULTS: Positive bcl-2 and p53
      expression was noted in 10 out of 36 (27%) and 14 out of 36 (39%) patients,
      respectively. Seven out of 11 tumors (63%) with bcl-2 expression responded
      completely to PDT vs. 6 out of 26 (23%) of cases with no bcl-2 expression (p =
      0.02). No association of p53, T-stage and of histology grade with response to PDT
      or PDT/RT was noted. The sensitivity to PDT of transformed human fibroblasts
      compared to normal ones was 4 times more at a fluence of 4.3 J/cm2 (4% vs. 1%
      cell kill) as well as at a fluence of 5.4 J/cm2 (8% vs. 2% cell kill).
      CONCLUSION: Bcl-2 protein expression is associated with favorable response to PDT
      and can be used as a predictor of cancer response to PDT. This finding can be
      explained by experimental studies showing that PDT induces selective degradation
      of the bcl-2 protein, leading to apoptosis by decreasing the bcl-2/bax ratio.
      Studies on PDT combination with agents targeting bcl-2 (i.e. taxanes) are on
      going to eventually assess a super-additive effect.

PMID- 11299824
TI  - Generation of cytotoxic effector lymphocytes by MLTC using tumor cells
      genetically modified to secrete interleukin-2.
AB  - The in vitro generation of effector lymphocytes cytotoxic to cancer cells, was
      investigated with a mixed lymphocyte-tumor culture (MLTC) system using
      genetically modified human cancer cells, followed by stimulation with the
      interleukin (IL)-2 plus immobilized anti-CD3 antibody (IL-2/CD3) system. A
      gastric cancer cell line, GC022588 (HLA-A2, 24, B35, 55, C1,3), was retrovirally
      transduced with the human interleukin (IL)-2 gene (GC/IL-2) or the neomycin
      resistance gene (GC/Neo). The secretion of biologically active IL-2 was
      detectable in GC/IL-2 cells but not in GC/Neo or parental GC022588 cells. The
      cytotoxic activity against the parental GC022588 cells of peripheral blood
      mononuclear cells (PBMC) was greater among PBMC activated with MLTC using GC/IL-2
      than among those activated with MLTC using GC/Neo or without MLTC. The IL-2/CD3
      stimulation could efficiently expand the effector lymphocytes without any
      reduction of the cytotoxic activity generated. The cytotoxic activity generated
      by this system was reproducible in several HLA-A2- or A24-positive donors. The
      effector lymphocytes could kill the other adenocarcinoma cells expressing HLA-A2
      or A24. The phenotypes of the effector lymphocytes generated with the system were
      40% CD4+ and 70% CD8+. Both phenotypes may have been responsible for the
      cytotoxicity. The removal of adherent cells from PBMC before the MLTC did not
      affect the generation of cytotoxicity, whereas neutralization of tumor-derived IL
      2 with a specific antibody during the MLTC significantly inhibited the generation
      of cytotoxicity. These results suggest that IL-2 gene-transduction augments the
      immunogenicity of the tumor cells that efficiently stimulate lymphocytes to be
      cytotoxic, and that the IL-2/CD3 system may be practical for the expansion of
      effector lymphocytes for use in adoptive immunotherapy for cancer. The mechanism
      by which IL-2 gene-modified tumor cells stimulate immune reactivity was
      discussed.

PMID- 11299825
TI  - Clinical application of low dose-rate brachytherapy combined with simultaneous
      mild temperature hyperthermia.
AB  - BACKGROUND: Recent biological research has shown that mild temperature
      hyperthermia (MTH) around 41 degrees C simultaneously combined with low dose-rate
      irradiation (LDRI) is an effective treatment modality for cancer. The aim of the
      study was to assess the clinical usefulness of a combination of MTH and
      simultaneous low dose-rate brachytherapy. MATERIALS AND METHODS: Seven
      superficial and 8 deep-seated tumors were included in this protocol. Two tumors
      had no previous treatment and the remainder were recurrent tumors which had
      arisen from previously treated sites. The average major diameters of superficial
      and deep tumors were 8.6 and 7.0 cm, respectively. The average values for Tmin in
      superficial and deep tumors were 41.5 and 40.7 degrees C, respectively.
      Brachytherapy was delivered by 137Cs and/or 192Ir LDRI sources. RESULTS: For
      superficial tumors, six of the seven tumors responded to the treatment (4
      achieved CR, 2 PR, 1 NC) and four tumors did not recur within the follow-up
      period of 5-15 months. All of the deep tumors responded and 5 achieved CR, 3 PR.
      Four tumors recurred 4-17 months after the treatment and the remainder showed no
      local recurrence within the follow-up period of 4-31 months. CONCLUSION: MTH
      simultaneously combined with LDRI was an effective method for treating
      progressive and bulky tumors with a previous treatment history.

PMID- 11299826
TI  - Technetium-99m-tetrofosmin scintigraphy in the prediction of chemotherapy
      response of untreated malignant lymphomas and comparison with other prognostic
      factors.
AB  - The aim of this study was to retrospectively predict the chemotherapy response of
      untreated malignant lymphomas using technetium-99m tetrofosmin (Tc-TF)
      scintigraphy and to compare the technique with other prognostic factors. In this
      study, before any chemotherapy, 25 patients with malignant lymphomas (ML)
      underwent Tc-TF scintigraphy. Scintigraphy was performed 10 minutes after
      intravenous injection of 20 mCi Tc-TF to calculate the tumor-to-normal (T/N)
      uptake ratio. In the first 1-2 years after complete chemotherapy, the response
      was evaluated by clinical and radiological methods. Compared with the 10 ML
      patients with poor chemotherapy response, the 15 ML patients with good response
      had a significantly higher mean T/N uptake ratio (3.23 +/- 0.56) versus 1.18 +/-
      0.11). All of the 15 patients with good response had positive scintigraphic
      results whilst the 10 patients with poor response had negative scintigraphic
      results. When compared with other prognostic factors, Tc-TF scintigraphy was the
      tool to predict the chemotherapy response of ML patients.

PMID- 11299827
TI  - Microvessel density (MVD) and vascular endothelial growth factor expression
      (VEGF) in human oral squamous cell carcinoma.
AB  - BACKGROUND: Carcinogenesis is thought to be dependent on neovascularization.
      Vascular endothelial growth factor (VEGF) is a glycoprotein that has the
      capability of increasing vascular proliferation and permeability. VEGF has been
      found to be expressed in several different types of tumours and it may contribute
      to the progression of malignant tumours. Increased microvessel density (MVD) has
      been described in oral squamous cell carcinoma (OSCC) and seems to be related to
      patient prognosis. MATERIALS AND METHODS: Fifty-two cases of OSCC were evaluated
      in the present study. Immunostaining for VEGF and Factor-VIII was performed. The
      MVD was evaluated in G1, G2 and G3 tumours. RESULTS: The differences between
      these 3 groups were statistically significant (p = 0.0331). MVD was also
      evaluated in lymph-node negative and lymph-node positive cases: the differences
      between these two groups were statistically significant (p < 0.0001). VEGF
      expression was evaluated in G1, G2 and G3 tumours. The differences between the 3
      groups were not statistically significant (p = 0.289), even if an increasing
      trend in the VEGF positivity was evident from G1 to G3. The difference of VEGF
      expression between tumours with and without lymph node metastases was not
      significant (p = 0.196). No correlation was present between intensity of VEGF
      positivity and histological grading or lymph-node status and between VEGF and
      MVD. CONCLUSION: Our data showed that MVD was correlated with grading and lymph
      node status, while no similar correlation was found for VEGF.

PMID- 11299828
TI  - Immunohistochemical detection of lymph node metastases in node-negative breast
      cancer patients.
AB  - BACKGROUND: Axillary lymph node metastases in breast cancer patients are one of
      the most important prognostic factors. Many previous studies have shown that in
      the detection of occult micrometastases immunohistochemical methods are superior
      when compared to routine hematoxylin-eosin staining. The aim of the study was to
      document the rate of missed occult micrometastases on routine hematoxylin-eosin
      staining in our department, in a retrospective study. PATIENTS AND METHODS: One
      hundred and one tumors of patients with breast cancer were included in this
      study. Immunohistochemical staining was performed using Pan-Cytokeratin AE1/AE3
      antibody. The number of nodes examined was 1301 (mean per patient: 12.9; range:
      one to 26). RESULTS: Of the 101 tumors studied, eleven had occult lymph node
      metastases detected by immunohistochemical methods. After repeated review by two
      independent pathologists, in two out of eleven patients lymph node metastases
      were confirmed even on hematoxylin-eosin staining. In nine out of eleven patients
      hematoxylin-eosin staining was not sufficient to detect occult micrometastases.
      CONCLUSION: Immunohistochemical methods enhance the detection rate of occult
      micrometastases in axillary lymph nodes of breast cancer patients and are
      recommended for routine diagnostic use in patients who have been diagnosed node
      negative on routine hematoxylin-eosin staining.

PMID- 11299829
TI  - Characterization of hilar lymph node by 18F-fluoro-2-deoxyglucose positron
      emission tomography in healthy subjects.
AB  - One hundred and seventy-nine images were collected from healthy subjects who
      underwent whole-body 18F-fluoro-2-d-deosyglucose positron emission tomography
      (FDG-PET) for health examination. Images showing visually increased FDG uptake
      based on a five-point visual scale in the hilar regions were included for
      analyses. We evaluated the sizes, standard uptake values (SUV), and lesion-to
      background (L/B) ratios of the hilar lymph nodes (HLN). Fifty of 179 (28%)
      subjects had visually increased FDG uptake in the hilar regions with a total of
      84 HLN. By a five-point visual scale, 67 out of 84 (79.8%) HLN were grade 2, 16
      out of 87 (19%) were grade 3, and 1 out of 84 (1.2%) was grade 4. The average
      size of the HLN was 1.55 x 1.46 cm. SUV of the HLN ranged from 1.132-2.975 with
      an average of 1.8 +/- 0.44. L/B ratio of the HLN ranged from 1.05-2.63 with an
      average of 1.52 +/- 0.39. Twenty-eight % of healthy subjects who underwent whole
      body FDG-PET demonstrated visually increased FDG uptake in the HLN. However, all
      of the 84 HLN had a size < 2 x 2 cm, SUV < 3.0 and L/B ratios < 3.

PMID- 11299830
TI  - C-myc amplification and cluster analysis in human gastric carcinoma.
AB  - The tumour samples ot 23 patients (9 male, 14 female, aged 28-85) were randomly
      selected for the study. DNA was isolated from paraffin embedded tissue for
      quantitative dot-blot hybridization, in order to determine the amplification
      values for the c-myc and K-ras oncogenes. The clinical and histological
      parameters studied were as follows: grade, TNM staging system, Lauren's
      histological type, localization and the severity of the disease. Amplified c-myc
      was found in 6 cases. Amplification was concomitant with c-myc overexpression
      detected with immunohistochemical staining. The amplification--9.1-fold on the
      average (ranging from 2.12 to 18.2) was significantly associated with the
      presence of distant metastasis (corr. coeff.: 0.5623, p < 0.01), but with none of
      the other parameters. No case with K-ras amplification was recorded. The result
      of the multivariate cluster analysis proved that age was the decisive factor in
      the segregation process. This age-related distribution (69 vs. 40, p < 0.001),
      however, did not coincide with either the incidence of distant metastasis or c
      myc amplification.

PMID- 11299832
TI  - Knee rotation-plasty for malignant musculoskeletal tumors occurring around the
      knee joint.
AB  - BACKGROUND: In addition to the wide excision of malignant musculoskeletal tumor
      around the knee joint, surgical methods, such as total knee arthroplasty and knee
      rotation-plasty are available. Therefore, this study was undertaken to clarify
      the usefulness of knee rotation-plasty. MATERIALS AND METHODS: At the Chiba
      Cancer Center, knee rotation-plasty was performed in 27 patients with malignant
      musculoskeletal tumor around the knee joint. Patients were divided into two
      groups: Group S, in which operations were performed as salvage surgery (8
      patients), and Group I, in which operations were performed as initial surgery (19
      patients). The lower limb function was investigated in 17 patients (7 patients in
      Group S and 10 patients in Group I). The lower limb function was assessed by the
      Knee Evaluation System of International Symposium on Limb Salvage and the Knahr's
      assessment. RESULTS: Lower limb function in Group S measured an average of 25.7
      points (85.6%), while the lower limb function in Group I measured an average of
      23.6 points (78.7%). The majority of patients in both groups were capable of
      walking without a cane or doing light exercise with below-the-knee prosthesis,
      revealing good lower limb function. CONCLUSION: Whether it is performed as
      salvage or initial surgery, knee rotation-plasty can be useful method for
      reconstruction of the knee after wide excision of malignant musculoskeletal tumor
      around the knee joint.

PMID- 11299831
TI  - Combination chemotherapy of cisplatin, methotrexate, vinblastine, and high-dose
      tamoxifen for transitional cell carcinoma.
AB  - BACKGROUND: We have previously demonstrated that tamoxifen enhanced the
      chemosensitivity of bladder cancer cells in vitro. In this pilot study, we tested
      the modulating effect of high-dose tamoxifen to conventional cisplatin,
      methotrexate, and vinblastine combination chemotherapy (CMV-T) for transitional
      cell carcinoma (TCC). PATIENTS AND METHODS: Between Nov. 1994 and Mar. 1999, 30
      TCC patients were enrolled. Nine patients had muscle-invasive bladder TCC; 21
      patients had either unresectable locally advanced diseases or distant metastases.
      CMV-T consisted of cisplatin 50 mg/m2/day, day 1 & 2; methotrexate 30 mg/m2/day,
      day 1 & 8; vinblastine 3 mg/m2/day, day 1 & 8; and tamoxifen 200 mg/m2/day, days
      1 through 4. RESULTS: A total of 98 courses had been given with an average of
      3.27 courses per patient (range: 1-7). Grade III/IV leukopenia and
      thrombocytopenia occurred in 18% and 21% of total courses, respectively. There
      were 7 episodes of neutropenic fever, and 3 patients died of sepsis. Non
      haematologic toxicities were generally mild. There was no venous thrombosis. Out
      of 26 patients eligible for evaluation of response, 1 complete and 14 partial
      responses with an overall response rate of 58% (95% confidence interval: 38-75%)
      were observed. The mean survival of all patients was 8 months. CONCLUSIONS: The
      toxicity of CMV-T chemotherapy is moderate, but generally manageable. The
      response rate of CMV-T for patients with advanced TCC seems to be only comparable
      to most conventional cisplatin-based combinations. The possible benefit of
      tamoxifen to enhance chemosensitivity of TCC needs further investigation.

PMID- 11299833
TI  - Detection of cervical lymph node metastases of nasopharyngeal carcinomas with
      technetium-99m tetrofosmin single photon emission computed tomography and
      comparison with computed tomography.
AB  - The purpose of this study was to evaluate the usefulness of technetium-99m
      tetrofosmin (Tc-99m TF) single photon emission computed tomography (SPECT) in the
      detection of cervical lymph node (LN) metastasis in nasopharyngeal carcinomas
      (NPC), and to compare Tc-99m TF SPECT results with computed tomography (CT)
      findings. Fifty patients with biopsy-proven NPC and suspected cervical LN
      metastases underwent head and neck Tc-99m TF SPECT and CT to detect cervical LN
      metastases. Cervical LN metastases of 40 patients were confirmed by
      histopathological examination of biopsy samples. For 22 LN lesions with
      discordant results between Tc-99m TF SPECT and CT, Tc-99m TF SPECT could
      correctly detect 4 metastatic and 7 benign LN lesions while CT could correctly
      detect 5 metastatic and 6 benign LN lesions. Agreement positive results of Tc-99m
      TF SPECT and CT could correctly detect all of the 18 metastatic LN lesions. Tc
      99m TF SPECT has a better specificity but a lower sensitivity for detecting
      cervical LN metastases in NPC when compared with CT. The combined use of Tc-99m
      TF SPECT and CT could significantly increase the accuracy of detect cervical LN
      metastases in NPC compared with the single use of either Tc-99m TF SPECT or CT.

PMID- 11299834
TI  - Nuclear volume and breast cancer prognosis.
AB  - BACKGROUND: In breast cancer, nuclear volume estimates can be expected to be
      better prognosticators than nuclear profile areas because biological variation is
      wider in volume estimates than in area measurements. MATERIALS AND METHODS: 191
      invasive breast cancer samples were available for nuclear volume measurements. To
      estimate the volume weighted mean nuclear volume, point-sampled linear intercepts
      were used on micrographs. The nuclear profile area was measured from 148 cases
      matching volume measurements and run by the Prodit morphometry program.
      Measurements were compared as prognosticators after a follow-up of 5 years. A
      computerized method on a randomly selected large number of nuclei was also
      applied in 17 cases. Bcl-2 immunostaining was compared with nuclear measurements.
      RESULTS: The correlation of volume and area measurements was statistically
      significant, but the correlation coefficients were low. The nuclear area showed a
      significant difference in survival at the 75 percentile cut-point but the volume
      weighted mean nuclear volume did not allow distinction of different prognostic
      groups. Computerized volume measurements based on a large number of nuclei and
      measurements based on the simpler method did not show statistically significant
      correlation. Bcl-2 staining did not show any correlation with volume or area
      measurements. CONCLUSIONS: Although the prognostic value of nuclear area was
      shown in our study, the volume-weighted mean nuclear volume did not show
      prognostic significance. Improvement of the methodology which could decrease
      method variation and increase reproducibility of measurements is urgent for
      verification of the prognostic value of nuclear volume measurements. Bcl-2
      immunostaining and nuclear area measurements were independent prognostic
      variables.

PMID- 11299835
TI  - Syndecan-1 expression in different soft tissue tumours.
AB  - BACKGROUND: In vitro studies have suggested that expression of syndecan-1 (CD138)
      is correlated with morphologic phenotype (epithelioid or spindle) of cultured
      tumour cells. MATERIALS AND METHODS: Fifty-seven different soft tissue tumours
      were selected to analyse their syndecan-1 (CD138) reactivity. Immunohistochemical
      staining of paraffin sections, following a high temperature unmasking technique,
      was performed. The intensity and the pattern of staining was studied. RESULTS:
      Cell membrane positivity was observed in epithelioid sarcomas and epithelial
      elements of synovial sarcomas. GISTs, some malignant epithelioid schwannoma and
      some fibromatosis showed intracytoplasmatic reaction, while pyogenic granuloma,
      Kaposi's sarcoma, fibrosarcoma and dermatofibrosarcoma protuberans were negative.
      CONCLUSION: At first it seemed that the cell membrane positivity of syndecan-1
      accompanied true epithelial differentiation in soft tissue sarcomas, but the
      results further highlighted the non specific nature of this expression. Therefore
      the heterogeneity in the appearance of syndecan-1 in various soft tissue tumours
      is not simply associated with the phenotype, suggesting more complex functions.

PMID- 11299836
TI  - Percutaneous US-guided radiofrequency ablation of hepatocellular carcinomas:
      results in 15 patients.
AB  - BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) cannot
      undergo surgery because of multifocality, location or advanced cirrhosis. Our
      experience with percutaneous radiofrequency ablation for treatment of patients
      suffering from unresectable hepatocellular carcinoma is described here. PATIENTS
      AND METHODS: Fifteen patients (ten men and five women) with eighteen primary
      hepatocellular tumors underwent percutaneous radiofrequency ablation. The mean
      diameter of the HCCs was 32 mm (ranging from 15 mm to 62 mm). The patients were
      treated under ultrasound guidance using either a 18-gauge internally cooled
      electrode or a 14-gauge electrode with four expandable hooks. RESULTS: Complete
      necrosis was achieved in 15 lesions after one session of RF ablation. The
      persistence of a small portion of viable tissue was seen in two lesions. One
      lesion was not evaluable. After a mean follow-up period of 9.2 months (range 3-24
      months), eleven patients (76%) showed no sign of local or distant recurrence, one
      patient developed a new lesion and one of two patients with persistence of viable
      tissue obtained a complete necrosis after the injection of percutaneous ethanol.
      Moreover, a major complication (intraperitoneal bleeding requiring surgical
      treatment) and three minor complications (1 pleuric effusion and 2 perihepatic
      fluid collections that resolved spontaneously) were observed. CONCLUSION: RF
      ablation is a simple, well-tolerated and effective procedure for the treatment of
      unresectable hepatocellular carcinomas.

PMID- 11299837
TI  - Immunohistochemical detection of p53 protein expression in breast cancer in young
      Kuwaiti women.
AB  - The mutation of the p53 gene is a common phenomenon in numerous human tumors
      including breast cancer. It leads to an accumulation of nonfunctioning p53
      protein in the cell nuclei, which can be detected by immunohistochemical
      techniques. In breast cancer overexpression of mutated p53 protein has been
      correlated to a poor prognosis. Our study is an immunohistochemical analysis of
      p53 in 82 cases of breast cancer in young (< or = 30 years old) Kuwaiti women,
      correlating it with histopathological grade, lymph node status, estrogen (ER) and
      progesterone receptor (PgR) content, tumor cell proliferation (immunostaining for
      Ki-67) and expression of c-erbB-2 oncoprotein. p53 immunostaining was found in 47
      (57.32%) of the carcinomas. 65% of them displayed positive immunostaining for c
      erbB-2. 63.7% of tumors with p53 overexpression were aneuploid. 64.8% of the p53
      positive tumors were node positive. 93.5% of the p53 immunopositive carcinomas
      were ER-negative, and in 95.7% of this subclass of patients no PgR could be
      detected. The vast majority of p53 positive carcinomas were grade III (76.6%),
      21.3% were grade II and 2.1% grade I, but neither tumor grade or tumor size
      showed a correlation with p53 expression. A significant negative correlation
      between ER- and PgR-content (p = 0.006) and immunostaining for p53 was observed.
      Our study provided evidence that the association of negative hormone receptor
      status and positivity for p53 immunostaining points to a greater tumor
      aggressiveness.

PMID- 11299838
TI  - Characteristics of cystic breast disease with special regard to breast cancer
      development.
AB  - BACKGROUND: This prospective study compares the characteristics of cystic disease
      of the breast (CDB) of patients who developed breast cancer (BCa) during the
      follow-up (1.25-4 years) period with those who did not. MATERIALS AND METHODS:
      K+, Na+, albumin, dehydroepiandrosterone (DHA), DHA-sulphate, oestrone,
      oestradiol, testosterone and progesterone levels were determined in breast cyst
      fluid (BCF). Patients presented data about their menstrual status, reproductive
      history, lactation period, date of first and the number of BCF aspirations,
      gynaecological interventions, use of oral contraceptives, family history of
      cancer, smoking habits and coffee consumption. The BCa incidence of patients was
      compared with the expected number of BCas in an age-matched group of 5143 women.
      RESULTS: Out of 147 patients 6 developed BCa. The standardized incidence rate was
      6.29. There were significant differences in testosterone, oestrone and
      progesterone levels and also reproductive history of patients who developed BCa
      compared with patients without BCa. CONCLUSION: The above markers outline a
      subgroup of patients with the highest BCa risk.

PMID- 11299839
TI  - Anti-p53 and anti-heat shock proteins antibodies in patients with malignant or
      pre-malignant lesions of the oral cavity.
AB  - BACKGROUND: Evaluation of circulating anti-p53 antibodies is an easy-to-perform,
      widely employed, procedure to assess the p53 status in cancer patients. MATERIALS
      AND METHODS: Levels of circulating anti-p53 antibodies in patients affected
      either by oral SCC or by pre- malignant oral lesions were assayed using a
      commercial ELISA kit. Autoantibody titers to Hsp60 and Hsp72 were determined by
      conventional ELISA. RESULTS: Anti-p53 antibodies were detected in 3 out of 16 SCC
      bearing patients (18.7%) and in 9 out of 13 patients suffering from pre-malignant
      oral lesions (69.2%). High titers of anti-Hsp60 autoantibodies were detected in 3
      out of 29 patients (10.3%), while in all patients anti-Hsp72 titers were in the
      normal range. CONCLUSION: The presence of anti-p53 antibodies in both SCC-bearing
      patients and in patients with pre-malignant lesions support the notion that p53
      gene mutation is an early event in oral tumorigenesis and suggest that this assay
      could be useful for diagnostic screening of pre-neoplastic lesions at high risk
      of recurrence and/or transition towards overt malignancy.

PMID- 11299840
TI  - Invading basal cell carcinoma of the jaw: an under-evaluated complex entity.
AB  - Basal cell carcinoma (BCC) is a locally invasive neoplasm, rarely metastatic, yet
      capable of significant local destruction and disfigurement. Invasion into the
      bone is uncommon and only a few cases of invasion into facial bones, but never to
      the mandible or maxilla, have been described. We report three patients with BCC
      lesions invading their jaws, as a consequence of which either their mandible or
      maxilla had to be partially resected. This resulted in facial mutilation which
      required comprehensive multi-disciplinary therapy to restore function and
      esthetics. Such therapy requires a combination of modalities offered by both
      plastic and maxillofacial surgeons, as well as oral and dental rehabilitators.

PMID- 11299841
TI  - Impact of intravesical chemotherapy on recurrence rate of recurrent superficial
      transitional cell carcinoma of the bladder: results of a meta-analysis.
AB  - BACKGROUND: The impact of in tranvesical chemotherapy on preventing recurrence of
      superficial transitional cell carcinoma of the bladder is controversial. The
      objective of this report is to present a meta-analysis of the available clinical
      trial data to quantify the effect of intravesical chemotherapy on tumor
      recurrence following trans-urethral resection (TURB) in patients with recurrent
      superficial bladder cancer. METHODS: A prospective study protocol outlining a
      meta-analysis was developed followed by a thorough search of the existing
      published literature using strict eligibility criteria. Eight randomized trials
      were found which met protocol specifications. These studies contained data on
      1,609 patients which were statistically combined using a fixed effects model
      (Peto). The outcome of interest was the proportion of patients with tumor
      recurrence at one, two and three years post-TURB. RESULTS: Combining all 8
      studies using 1 year recurrence as the outcome measure yielded a Peto odds ratio
      (ORp) of 0.62, demonstrating a 38% reduction in one year recurrence among
      patients treated with intravesical chemotherapy versus TURB alone. Using 2 and 3
      year recurrence as the outcome measure yielded ORp's of 0.46 and 0.35
      respectively, favoring TURB + intravesical chemotherapy versus TURB alone. A
      statistical test for heterogeneity (Q) showed the 2 and 3 year outcome data to be
      heterogeneous (i.e. the studies are not measuring an effect of the same
      magnitude). Sensitivity analyses showed that drug type appeared to account for
      the observed heterogeneity with a stratified analysis demonstrating that
      adriamycin is less effective in reducing subsequent tumor recurrences than all
      other drugs studied. CONCLUSION: Intravesical chemotherapy appears to have a
      major impact on decreasing the chance of recurrence of recurrent superficial
      bladder cancer. Three year recurrence is decreased by as much as 70% when
      compared with TURB alone. These data are in contrast to prior analyses suggesting
      only modest efficacy of such treatment in this clinical setting.

PMID- 11299842
TI  - Differential expression of the drug resistance markers DNA topoisomerase II alpha
      and glutathione S-transferase-pi in the histological compartments of Wilms'
      tumors.
AB  - More than 80% of the patients presenting with Wilms' tumor can be cured today.
      Some patients, however, fail to respond to chemotherapy. The objective of this
      study was to analyze the immunohistochemical distribution of two markers of
      cytostatic drug resistance, e.g. DNA topoisomerase II alpha (Topo II alpha) and
      glutathione S-transferase-pi (GST-pi) in 23 Wilms' tumor patients who had
      undergone an operation between 1984 and 1997. Eight patients had stage I disease,
      seven stage II, three stage III, four stage IV, and one stage V disease. Five
      tumors showed high malignancy histology. Investigations were carried out on
      formalin-fixed and paraffin-embedded tissue sections using the indirect
      immunoperoxidase method. Topo II alpha was predominantly present in the
      epithelial components of the specimens. It was more frequently found in
      anaplastic tumors. There was no difference in the presence of Topo II alpha in
      the epithelial components between specimens derived from treated and untreated
      patients. Topo II alpha was, however, less expressed in the blastemal and stromal
      elements of specimens after preoperative treatment. If GST-pi was present, it was
      confined to the epithelial components except for one case. While no expression of
      GST-pi was found in preoperatively untreated Wilms' tumors, it was present in
      epithelial compartments in 57% of tumors after chemotherapy. In conclusion,
      preoperative chemotherapy led to compartment-specific alterations in the
      expression levels of both markers indicating a contribution to treatment response
      of Wilms' tumors.

PMID- 11299843
TI  - A phase II study of subcutaneous low-dose interleukin-2 plus erythropoietin in
      metastatic renal cell carcinoma progressing on interleukin-2 alone.
AB  - OBJECTIVE: The activation of angiogenesis has been proven to suppress the anti
      cancer immunity. The evidence of abnormally high pretreatment blood levels of
      vascular endothelial growth factor (VEGF), which is the main angiogenic factor,
      has appeared to predict resistance to IL-2 immunotherapy of metastatic renal cell
      carcinoma (RCC). Therefore, the control of VEGF secretion could influence the
      efficacy of IL-2. Recent data suggest that erythropoietin (EPO) may modulate VEGF
      secretion and IL-2 biological activity. On this basis, a study was planned with
      subcutaneous (s.c.) low-dose IL-2 plus EPO in metastatic RCC, which had
      progressed on IL-2 alone (6 million IU/day for 6 days/week for 4 weeks). METHODS:
      Patients received IL-2 at the same dose as the previous cycle, plus EPO (10,000 3
      times/week until the end of IL-2 therapy. Serum levels of VEGF were measured by
      enzyme immunoassay on venous blood samples collected at weekly intervals. The
      study included 12 evaluable metastatic RCC patients. RESULTS: The treatment was
      well-tolerated and most patients referred a relief of IL-2-induced asthenia. A
      partial response (PR) and 4 stable diseases (SD) were achieved on IL-2 plus EPO,
      whereas the other 7 patients had a progressive disease (PD). Hemoglobin mean
      levels were significantly higher on IL-2 plus EPO than during the previous
      therapy with IL-2 alone in the same patients. In the same way, mean lymphocyte
      increase was higher on IL-2 plus EPO than on IL-2 alone, even though this
      difference was not significant. Finally, VEGF increase was significantly lower on
      IL-2 plus EPO than during IL-2 alone. CONCLUSION: This preliminary study shows
      that the concomitant administration of EPO may allow a control of the neoplastic
      growth in advanced cancer patients progressing on IL-2 alone, reduce the
      subjective toxicity, prevent hemoglobin decrease and counteract IL-2-related VEGF
      increase.

PMID- 11299844
TI  - Goserelin (Zoladex) or orchiectomy in metastatic prostate cancer? A quality of
      life and cost-effectiveness analysis.
AB  - BACKGROUND: We have today two treatment alternatives (orchiectomy or LHRH
      analogue) in metastatic prostate cancer offering the same expectations of
      survival. This study documents the quality of life (QoL) and cost-effectiveness
      of these alternatives. PATIENTS AND METHODS: 65 consecutive patients treated at
      the University Hospital of Tromso (UHT), Norway, between 1994 and 1999 were
      registered. At evaluation, 45 patients (LHRH-analogue--15 patients, orchiectomy-
      30 patients) were alive and included in the QoL-study (EORTC QLQ C-30, QoL 15D).
      45 patients were followed-up at the UHT and included in the cost-analysis. Costs
      were calculated for a 36-month interval and converted to British pounds (1 Pound
      = 13 NOK). A 5% d.r. was employed. RESULTS: The mean QoL (15D) was 76.4
      (orchiectomy) and 72 (LHRH) (0-100 scale). Constipation, urinating problems,
      fatigue, pain and loss of sexual functioning were the dominant symptoms. The
      treatment costs per patient treated were 8,895 Pounds (orchiectomy) and 10,937
      Pounds (LHRH-analogue). The crossover in cost was located at 25 months. A
      sensitivity analysis varying discount rate (0-10%), drug charges (25-50% off) and
      treatment time (12-18 months) did not alter the conclusion. CONCLUSION:
      Orchiectomy is the treatment of choice when life expectancy is more than two
      years.

PMID- 11299845
TI  - Doxorubicin followed by docetaxel versus docetaxel followed by doxorubicin in the
      adjuvant treatment of node positive breast cancer: results of a feasibility
      study.
AB  - BACKGROUND: Doxorubicin (A) and Docetaxel (T) are amongst the most active agents
      in breast cancer treatment. The impact of drug sequencing is an issue still under
      evaluation. OBJECTIVE: To evaluate the feasibility and tolerability of two A and
      T-based sequential regimens, in which the sequence of drug administration was
      reversed. METHODS: The study included patients pts aged < or = 70 years, with
      operable node positive breast cancer. Two consecutive groups of patients received
      one of the following regimens: 1) Sequential A-->T-->CMF: Doxorubicin 75 mg/m2,
      i.v., day 1, q3wks x 3 cycles, followed by Docetaxel 100 mg/m2, i.v., day 1,
      q3wks x 3 cycles, followed by i.v. CMF days 1 and 8 q4wks x 3 cycles. 2)
      Sequential T-->A-->CMF: same doses for Doxorubicin and Docetaxel but reverse
      sequence of administration, followed by oral CMF (CPA 100 mg/m2, oral, days 1-14
      + MTX 40 mg/m2, i.v., days 1 and 8 + 5FU 600 mg/m2, i.v., days 1 and 8, q4wks).
      An analysis of treatment administration and toxicity was performed for the first
      six cycles of CT, in the two treatment groups. RESULTS: Group 1 with 20 patients
      and group 2 with 14 patients were balanced in terms of patient and tumour
      characteristics. There was one early treatment discontinuation in each group due
      to toxicity (one allergic and one skin reaction to docetaxel). Median relative
      dose intensity was 100% for both drugs in both groups. The most relevant side
      effects were (overall incidence, group 1 vs group 2): Myalgia: 45% vs 72%;
      Arthralgia: 15% vs 57%; Skin: 35% vs 57%; Neurosensory: 55% vs 64%; Stomatitis
      65% vs 36%; conjunctivitis 25% vs 57%; Neutropenic Fever 20% vs 21% and Fatigue
      80% vs 93%. Grade 3/4 adverse events' rate was low in the two groups.
      CONCLUSIONS: 1) Both sequences were estimated feasible due to the optimal
      treatment administration and limited incidence of G3-G4 side effects. 2) The
      concomitant use of lenograstin might partially explain the reported incidence of
      myalgia and arthralgia. 3) No conclusion can be drawn on the most tolerable
      regimen due to the limited number of patients.

PMID- 11299846
TI  - Papilloma virus and c-erbB-2 expression in diseases of the mammary nipple.
AB  - PURPOSE: The detection of low/intermediate/high risk genital groups of human
      papillomavirus (HPV) in correlation with a growth-factor receptor c-erbB-2 in
      benign tumors of the mammary nipple. MATERIALS AND METHODS: Ten nipple duct
      adenomas (NDAs) and twenty papillomas, all embedded in paraffin and taken from
      the breast, were analyzed for HPV DNA of the low- and high/intermediate-risk
      groups. Polymerase chain reaction (PCR) with HPV consensus primers (types
      6/11/16/18/33) and dot-blot hybridization with type-specific primers were used
      for the detection of these HPV-DNA sequences. Indirect in situ PCR (ISPCR) was
      also used in one case of an HPV-DNA-positive papilloma. In addition, we examined
      c-erbB-2 oncogene expression in NDAs and central carcinomas of the mamma from an
      immunohistochemical perspective. RESULTS: Using PCR and dot-blot hybridization we
      could not detect the gene sequences that are specific for the low- and
      high/intermediate-risk groups in any of the ten NDAs. Regarding the 20 cases of
      papilloma, a positive result for HPV types 6/11 was detected by indirect ISPCR;
      in one case in combination with a condyloma of the skin around the mammary
      nipple. The oncogene expression of c-erbB-2 displayed a strong signal in the
      papilloma cells and in the NDAs of the breast. CONCLUSION: Our results showed
      that the HPV-DNA types of the low- and high/intermediate-risk groups are without
      relevance for the pathogenesis of benign diseases of the nipple. It was,
      therefore, not possible to establish a correlation between the oncogene
      expression of c-erbB-2 and the HPV-DNA types.

PMID- 11299847
TI  - Paclitaxel-carboplatin chemotherapy does not cause encephalopathy in patients
      with ovarian cancer: a prospective EEG mapping study in 28 patients.
AB  - BACKGROUND: The objective of this study was to evaluate possible effects of a
      paclitaxel containing chemotherapy, on the central nervous system (CNS) in women
      with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with
      histologically documented epithelial ovarian carcinoma and treated with a
      combination chemotherapy consisting of paclitaxel and carboplatin entered the
      study. Patients were tested with resting EEG (R-EEG) before and after
      chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy
      (71%). Eleven patients (39%) developed peripheral neurotoxicity. A decrease of
      beta power and an increase of delta and theta power as well as a deceleration of
      the total centroid frequency clearly demonstrated a reduced vigilance in patients
      with ovarian cancer compared to healthy controls. On the other hand, the observed
      increase of beta power, a decrease of delta and theta power, and an acceleration
      of the total centroid from pre- to post-treatment demonstrated an improvement of
      vigilance in patients with ovarian cancer after treatment with
      paclitaxel/carboplatin. CONCLUSIONS: The results of this study suggest that
      chemotherapy consisting of paclitaxel and carboplatin does not cause adverse
      effects on the central nervous system. Improved vigilance was measured in
      patients with ovarian cancer after chemotherapy.

PMID- 11299848
TI  - Serum levels of angiogenin (ANG) in invasive cervical cancer and in cervical
      intraepithelial neoplasia (CIN).
AB  - BACKGROUND: The propensity of malignant tumors to increase in size, to invade
      locally and to metastasize is dependent on angiogenesis, which is induced by a
      variety of proteins including the family of fibroblast growth factors, vascular
      endothelial growth factor and angiogenin (ANG). The aim of the present study was
      to measure the serum levels of ANG in patients with CIN and invasive cervical
      cancer and to evaluate a possible correlation between ANG and various
      clinicopathologic parameters. MATERIALS AND METHODS: Blood was collected from 62
      patients with invasive cervical cancer and 47 patients with CIN. Serum samples of
      30 age-matched healthy women acting as a control group were obtained.
      Determination of serum levels of ANG was performed using a quantitative human ANG
      immunoassay. RESULTS: The overall median ANG serum level was 272.0 pg/ml (range
      101.6-869.2). The median serum levels of ANG were 248.9 (range 101.6-307.2) for
      healthy female controls, 246.8 (range 169.7-468.1) for patients with CIN and
      308.1 pg/ml (range 180.1-869.2) for patients with invasive cervical cancer. Serum
      levels of ANG were significantly elevated in patients with invasive cervical
      cancer compared with patients with CIN (p < 0.05) as well as healthy female
      controls (p < 0.05). No difference was found between ANG serum levels in women
      with CIN, and healthy controls (p < 0.05). No correlations were found between
      serum levels of ANG and clinico-pathologic parameters (p > 0.05). CONCLUSIONS:
      Our data indicate the important role of ANG in tumor angiogenesis in invasive
      cervical cancer as ANG serum levels were significantly elevated in these
      patients. However, elevated ANG serum levels seem to occur only after the
      transformation from pre-invasive to invasive lesions.

PMID- 11299849
TI  - Gastric carcinomas of intestinal type concur with distant changes in the gastric
      mucosa. A multicenter study in the Atlantic basin.
AB  - Population studies in the Pacific Basin showed that gastric carcinomas of
      intestinal type often concur with distant mucosal changes (DMCs). In the present
      work, the presence of DMCs was investigated in populations dwelling in the
      Atlantic Basin. A total of 1737 gastrectomy specimens were reviewed: 627 in New
      York, 435 in Reykjavik, 198 in Buenos Aires, 186 in Florence, 174 in London and
      the remaining 117 in Stockholm. A total of 17,282 sections were carefully
      scrutinized. The following DMCs were investigated: intramucosal glandular cysts,
      gastric cells with ciliated metaplasia, with large or small mucus negative
      vacuoles, and extensive intestinal metaplasia (IM). The highest frequencies of
      DMCs were found in Florence for specimens with intestinal type carcinoma: 41.3%
      had intramucosal cysts, 22.4% had cells with ciliated metaplasia, 12.9% cells
      with large vacuoles, and 50.9% had high IM. The highest frequency of gastric
      cells with small vacuoles was recorded in New York (9.1%), also in specimens with
      intestinal type carcinoma. Significantly lower DMCs percentages were found in
      specimens with carcinomas of diffuse type, and miscellaneous gastric diseases.
      The occurrence of DMCs was not influenced to a significant degree by the number
      of sections available per gastrectomy. Since environmental factors trigger the
      evolution of intestinal type carcinomas and as DMCs also occurred in specimens
      without carcinoma-although at a significantly lower rate--it is conceivable that
      DMCs are also evoked by environmental factors (before a gastric carcinoma
      ensues). DMCs were found in specimens having intestinal carcinomas either in the
      cardia, the corpus or the antrum. Thus, DMCs seem to provide the adequate "soil"
      for the development of gastric carcinomas of intestinal type, independently of
      the future localization of that tumor in the stomach.

PMID- 11299851
TI  - [Nursing in community-based psychiatric institutions].

PMID- 11299850
TI  - Expression of metastasis associated proteins, CD44v6 and NM23-H1, in pediatric
      acute lymphoblastic leukemia.
AB  - Two metastasis-associated proteins, CD44v6 and NM23-H1, are expressed by normal
      lymphoid cells, the former serving as activation marker and the latter as a
      constitutive protein. CD44v6 is considered as a marker of poor prognosis of
      various hematological cancers but its expression was not demonstrated in
      childhood acute lymphoblastic leukaemia (ALL). On the other hand, NM23-H1 is
      considered as a differentiation inhibitory factor in various hematological
      cancers and as a marker of poor prognosis. Therefore we analyzed the expression
      of CD44v6 and NM23-H1 in the bone marrow of sixteen pediatric ALL patients using
      immunocytochemistry. For the first time, we have demonstrated the expression of
      CD44v6 protein epitopes on leukemic cells in a proportion of ALL cases (6 out of
      16), primarily in the medium/high risk group (except one case), suggesting a
      possible association to an unfavourable outcome. On the other hand, NM23-H1
      protein expression was maintained in leukaemic cells in 50% of both low and
      medium/high risk ALL cases. The majority of the pediatric ALL cases expressed
      only one of the metastasis-associated proteins (10 out of 16). This feature is
      similar to the observations made in several adult solid cancers. The potential of
      CD44v6 expression in leukaemic cells as prognosticator in pediatric ALL should be
      evaluated in a larger clinical trial.

PMID- 11299852
TI  - [Ambulatory sociotherapy--a new task for psychiatric nursing].

PMID- 11299853
TI  - [Health promotion--changes in prospectives of psychiatry].

PMID- 11299854
TI  - [From top to toe: guidelines for color and style].

PMID- 11299855
TI  - [Therapeutic possibilities in Alzheimer disease. I--Drug therapy].

PMID- 11299856
TI  - [Mobbing in hospital and nursing].

PMID- 11299857
TI  - [CT-guided percutaneous drainage in the treatment of acute necrotizing
      pancreatitis].
AB  - The authors analysed the results of the treatment of 24 patients with acute
      necrotizing pancreatitis. Besides intensive and operative treatment prophylactic
      antibiotics, early naso-jejunal feeding, CT guided percutaneous peripancreatic
      drainage are favourable to avoid septic complications and to postpone the first
      operation. In 11 patients percutaneous drainage was performed. Using percutaneous
      drainage three patients (33.3%) recovered without operation, the mean drainage
      time was 23.4 days. The first operation could be postponed in the other 8
      patients after percutaneous drainage. No complications occurred as result of the
      interventions, although in one patient the drain slipped out spontaneously. Due
      to the complex treatment the total mortality rate was 12.5%.

PMID- 11299858
TI  - [The role of percutaneous radiologic interventions in the treatment of pancreatic
      pseudocysts].
AB  - Authors evaluate the indications and results of percutaneous puncture and
      drainage of pancreatic pseudocysts. The interventions were performed in 20
      patients. The first line treatment is usually surgical. Percutaneous drainage or
      aspiration is suggested if the patient is symptomatic, the size of pseudocyst is
      between 3 and 6 cms and when it can be punctured using radiological procedures,
      without the risk of damaging other organs. Previous peripancreatic operation,
      high-risk surgical intervention and the refusal of the operation by the patient
      should also be considered. Percutaneous drainage is an alternative method for the
      treatment of pancreatic pseudocysts. The advantages of this procedure are: It is
      minimally invasive, complications are rare and reintervention is possible.
      Disadvantage is high risk of recurrence.

PMID- 11299859
TI  - [Clinical value of "zero-hour" biopsy in kidney transplantation].
AB  - We have performed 115 "zero-hour" biopsies of transplanted kidneys since 1994.
      Donor kidneys were divided into five groups, based on the morphological findings
      of "zero-hour" biopsies. No morphological abnormalities were found in 38.26% of
      the cases (group 1). Arteriolosclerosis was present in 22.61% of donor kidneys
      (group 2). Specific morphological alterations, i.e. acute tubular necrosis
      (24.35%), tubulointerstitial nephritis (5.22%) or glomerulonephritis (9.56%) were
      detectable in the remaining cases (groups 3-5). During an average of 644 days
      after transplantation clinical and histological follow-up were performed.
      According to our observations: 1. Higher creatinine was found in patients with
      grafts with arteriolosclerosis (group 2). 2. There were more non-viable grafts
      and longer periods of delayed graft function in patients with acute tubular
      necrosis (group 3). 3. Higher serum creatinine, more frequent rejections with the
      need of secondary hemodialysis were observed in patients who received a kidney
      with "zero-hour" biopsy of tubulointerstitial nephritis (group 4). 4. The only
      complication observed in patients with glomerulonephritis donor kidneys was
      delayed functioning of the graft (group 5). Biopsies did not cause complication
      in any of our patients. In conclusion, "zero-hour" biopsies can be useful and
      safe tools to predict early graft function. Besides, "zero-hour" biopsies help
      histological interpretation of consecutive graft re-biopsies.

PMID- 11299860
TI  - [Cholestasis caused by chronic pancreatitis in childhood. Surgical treatment and
      genetic analysis].
AB  - Authors report two cases of childhood chronic pancreatitis, causing severe
      symptoms and common bile duct stenosis with cholestasis. Both patients had to be
      operated on. Chronic pancreatitis with calcification led to significant common
      bile duct stenosis in a 13 years old girl. After ERCP a double bypass procedure
      was performed (Wirsungo-jejunostomy and hepatico-jejunostomy). During 42 months
      follow-up the patient remained pain- and symptom-free gaining 16 kilograms. In a
      9 years old girl severe stenosis of the intrapancreatic common bile duct and a
      small duct type chronic pancreatitis with extensive fibrosis was found. Treatment
      was Roux-en-Y hepatico-jejunostomy. Thirty-four months after the operation she is
      symptom-free with normal enzyme parameters. Authors report results of genetic
      investigations performed on registered chronic pancreatitis children and their
      families in Hungary, including the two operated cases. Two of the 5 patients were
      hereditary type, despite negative family history. Cationic trypsinogen gene R122H
      (R117H) mutation were detected in both patients. Chronic non-hereditary
      pancreatitis is a very rare disease in childhood but may cause severe secondary
      conditions requiring surgery.

PMID- 11299861
TI  - [Experience with the surgical management of Vater's ampulla tumors].
AB  - The article reviews our experience about tumours of the papilla of Vater. 30
      patients were operated on between 1996-1999. The mean age was 58 years, the
      leading symptom (73%) was jaundice. In 23 patients preoperative ERCP was
      successful and was completed in 15 cases with EST, in 8 cases with biliary
      drainage. In 3 patients--despite benign endoscopic histology--intraoperative
      frozen section, and in one patient final histology confirmed malignancy.
      Altogether in 27 patients was malignant transformation of the papilla observed.
      In 15 cases pylorus-preserving pancreatoduodenectomy (PPPD), in 2 cases local
      excision (LE), while in 10 patients palliative procedures were performed.
      Resection rate (PPPD + LE) was 63%, while radical resection (PPPD) was performed
      in 55.5% of all cases. During 26 months mean follow-up survival rate was
      altogether 74%, and 80% in radically resected patients. We review the literature,
      describe the difficulty of histological and describe our experience and practice
      in the treatment of this rare tumour.

PMID- 11299862
TI  - [What to take into consideration in surgery of patients with artificial valve or
      pacemaker?].

PMID- 11299863
TI  - [Arterial thrombolysis in peripheral arterial occlusions--where are the limits of
      the realm and what are the responsibilities of a vascular surgeon?].
AB  - Arterial thrombolysis is a well established treatment for acute myocardial
      ischaemia, with respectable results. It is gaining ground in peripheral vascular
      surgery as well, particularly in the treatment of acute ischaemia due to
      occlusion of a sclerotic artery or an arterial graft. However, in case of
      myocardial ischaemia diagnosis (coronary angiogram), treatment (thrombolysis,
      PTCA or revascularisation) and recognition for the need for acute surgical
      treatment are in the same hands in cardiology, in case of peripheral arterial
      occlusions diagnostics (and therapy in some extent) are provided by radiologists,
      while patients are usually referred to vascular surgeons. They can provide
      limited diagnostics (intraoperative angiogram) and can treat patients by non
      surgical means (i.e. intraoperative thrombolysis). Although co-operation between
      radiology and vascular surgical services is crucial and can save limbs and lives,
      in everyday practice we frequently have to decide whether the ischaemic limb can
      be treated by thrombolysis only (carried out by radiologists) or the extent and
      stage of ischaemia are such that they require the faster surgical reconstruction,
      often completed with intraoperative angiogram and thrombolysis. Whose decision
      should it be? Should vascular surgeons force thrombolysis, should they do it
      themselves? What are the cost implications of the successful and unsuccessful
      thrombolysis?

PMID- 11299864
TI  - [Infection register at a surgical department in Hungary].
AB  - An infection register processing 905 surgical site infections followed after
      33,426 operative interventions in a 20-year period between 1977 and 1996 is
      described. The preliminaries of modern infection surveillance both abroad and in
      Hungary are outlined. The method of registration and evaluation used by the
      authors are also outlined in details. The results divided into two 10-year and a
      20-year groups. They are documented in several tables and linear regression
      diagrams. The infection rates are the following: 1977-1986: Category "A": 0.4%,
      Category "B": 1.9%, Category "C": 4.0%, Category "D": 19.3%; 1986-1996: Category
      "A": 0.6%, Category "B": 2.5%, Category "C": 0.9%, Category "D": 4.4%. There were
      slight increases in the categories "A" and "B" during the second decade, but they
      were not significant. On the other hand during the same period significant
      decrease in the infection rates was observed in groups "C" and "D". Rates of the
      superficial, deep and regional infections were also separately investigated. The
      same tendencies could be observed as above. The data had been compared with the
      recommendations of the Advisory Board of the Infectious and Tropical Diseases
      dated in 1994, and against the Hungarian HELICS study in 1995. Infection rates
      analysed in the register were lower in every categories. Based on the experience
      the authors have the opinion, that until one of the multicentric surveillance
      system (e.g. HELICS) will be broadly accepted, the prospective registration
      method used by the authors, though it is less complex, can also be effective in
      preventing surgical infections.

PMID- 11299865
TI  - [Gastric pouch with preserved duodenal passage: attempt to optimize
      reconstruction after total gastrectomy].
AB  - A new method--aboral pouch with preserved duodenal passage--has been introduced
      for reconstruction after total gastrectomy. After excising the stomach,
      preparation of the Roux loop and construction of an end-to-side esophago
      jejunostomy, the Roux loop is anastomosed to the duodenal stump side-to-end
      approximately 40-50 cm distal from the esophago-jejunostomy. Right beneath this
      second anastomosis the Roux limb is closed with a stapler to provide
      unidirectional passage through the duodenum. An aboral pouch is constructed by a
      15 cm long side-to-side anastomosis between the Roux limb under the stapled
      segment and the aboral end of the Y limb. The advantages of both the reservoir
      constructing and the interposition methods (duodenal passage preserved) are
      combined with this new form of reconstruction. The additional benefit is that the
      reservoir is constructed in aboral position, as previously suggested by the
      authors.

PMID- 11299867
TI  - [Oncocytic carcinoid tumor of the lung].
AB  - An elderly female patient was admitted and operated on for a lesion in the upper
      lobe of the right lung. After lobectomy the patient has recovered without
      complications. Histology proved oncocyter carcinoid tumour. This neuro-endocrine
      tumour is a rarity in the lungs with less than forty cases reported in the
      reviewed literature. This is the first case reported in Hungary.

PMID- 11299866
TI  - [New surgical method in the treatment of severe hemorrhoidal bleeding caused by
      decompensated liver cirrhosis].
AB  - Authors used a new technique for haemorrhoid surgery performed with PPH
      (Procedure for Prolapse and Haemorrhoids) instrument to cure bleeding
      haemorrhoids caused by vascularly decompensated liver cirrhosis. Longo developed
      the special circular stapler in 1993. The 69 years old female patient underwent
      continuous medical treatment during the last 10 years due to liver cirrhosis
      developed as a result of chronic alcoholism. There were two haemorrhoidectomies
      in her previous history. Haemorrhoidal bleed was in the background of severe
      haematochesia in July 1999. She was transfused with 38 units of blood at
      Department of internal medicine. Because no result was expected by further
      conventional surgery, this new procedure was performed. After uneventful
      postoperative period the patient was discharged without any complaints. During
      six months follow-up there was no further bleeding and her quality of life is
      better.

PMID- 11299868
TI  - [Paraesophageal hiatal hernia complicated with stomach cancer].
AB  - The authors present the history of a 79 years old female patient who had to be
      operated on with paraesophageal hiatal hernia causing cahexia, hematemesis,
      dysphagia and pain. They found an upside down stomach with cancer inside. They
      emphasize that endoscopy is very important in the diagnostic process and that
      cancer can develop even if the stomach is located in the chest.

PMID- 11299870
TI  - [Angiomorphologic indications for emergency carotid reconstruction].
AB  - The authors examine, whether urgent carotid reconstruction is indicated, when a
      patient is neurologically in stable condition, but unstable angiomorphologically.
      PROCEDURE: The authors examined data about 101 patients (out of 720 carotid
      reconstructions). These patients had surgery for bigger than 90% stenosis on one
      of their internal carotid arteries, in 1998 at the Cardiovascular Department of
      the Semmelweis University Budapest. Nowadays reconstruction on the internal
      carotid artery is a routine procedure, but the indication for emergency operation
      is still controversial. We re-examined our emergency carotid operations in a
      retrospective study, in which surgery was based on angiomorphological
      indications. 74 patients were operated electively and 27 patients urgently. The
      first group waited for the operation 1-5 days, and they received preventative
      medical treatment. There were no preoperative TIAs. In both groups 1
      perioperative TIA occurred. The authors conclude, that emergency carotid
      endarterectomy is not necessary based only on angiomorphological indication.
      Careful preoperative preparation is suggested, and until surgery anticoagulation
      or antiaggregation treatment is necessary. The preoperative stroke incidence at
      emergency carotid reconstruction is higher than is at electively operated
      patients.

PMID- 11299869
TI  - [Monitoring of oxidative stress after experimental small bowel
      autotransplantation].
AB  - The difficulty at transplanting the small bowel mainly is caused by the biology
      of the intestine. It is highly immunogenic, is one of the most sensitive tissues
      to ischemia-reperfusion injury. Our aims were to investigate changes of oxygen
      free radical mediated reactions after autotransplantation at different
      preservation times and perfusion fluids. Our results prove that this model is
      feasible to examine ischemia-reperfusion injury in the small intestine. Euro
      Collins (EC) is a suitable preserving solution for small bowel transplantation.
      There was no significant lipid peroxidation within the first 6 hours of graft
      preservation. However superoxide dismutase (SOD) activity was dramatically
      reduced during reperfusion in the tissues samples. Significant increase of
      reduced glutathione at the same time can be explained by compensatory mechanism
      to neutralize increased free radical production.

PMID- 11299871
TI  - Promoting community-based research ventures.

PMID- 11299872
TI  - Catholic hospital's website is an award-winner.

PMID- 11299873
TI  - Ministry and postmodernism. The new age has both positive and negative
      implications for Catholic health care.

PMID- 11299874
TI  - Returning to revenue growth. A new series examines five revenue growth strategies
      in a difficult health care market.

PMID- 11299875
TI  - Genetics and ethics. Issues and implications of the Human Genome Project.

PMID- 11299877
TI  - Genetics and ethics. Is the ministry prepared to answer ethical questions raised
      by the Human Genome Project?

PMID- 11299876
TI  - The Human Genome Project. Recent genetic advances will have far-reaching
      implications for Catholic health care.

PMID- 11299878
TI  - Prenatal genetic testing. The potential loss of human dignity will demand a
      consistent ethical response from Catholic health care.

PMID- 11299879
TI  - Personal privacy and the common good. Genetic testing raises ethical
      considerations for both patients and clinicians.

PMID- 11299880
TI  - Jurisprudence and genetics. Law governing the new technologies should be grounded
      in a moral vision.

PMID- 11299881
TI  - Genetic testing and discrimination. How can we protect job and insurance policy
      applicants from negative test consequences?

PMID- 11299882
TI  - Genetic testing's "soft underbelly". Christian vision and bio-utopia.

PMID- 11299883
TI  - The challenge of genetics.

PMID- 11299884
TI  - The dignity and vocation of the human person. A Christian bioethical vision.

PMID- 11299885
TI  - Community networks. Partnerships between Catholic charities and Catholic health
      care organizations. Mercy Brown Bag Program, Oakland, CA.

PMID- 11299886
TI  - Glossary of common terms in genetics.

PMID- 11299887
TI  - The continuing need for ministry leadership development.

PMID- 11299888
TI  - Patients think you're a miracle worker? Watch out!

PMID- 11299889
TI  - Elbow-to-elbow with my NP "roommate".

PMID- 11299890
TI  - How patients' emotions can unlock a diagnosis.

PMID- 11299891
TI  - Snappy comebacks to sneaky lawyer questions.

PMID- 11299892
TI  - Where do you stand on the pay scale?

PMID- 11299893
TI  - Who'll be calling the shots on health care?

PMID- 11299894
TI  - The HIPAA rules change once more.

PMID- 11299895
TI  - Doctor discipline--or "medical McCarthyism"?

PMID- 11299896
TI  - My malpractice case was literally a trial by fire.

PMID- 11299897
TI  - Want to boost revenue? Mount a collections campaign.

PMID- 11299898
TI  - Will primary care lead the way to universal coverage?

PMID- 11299899
TI  - When form follows function in laboratory design, operational savings follow.

PMID- 11299901
TI  - Conflict in the laboratory II.

PMID- 11299900
TI  - What to watch for in the next three years as the Internet transforms the health
      care landscape.

PMID- 11299902
TI  - Employee conscientious objection.

PMID- 11299903
TI  - Dollar$ & $en$e. Part V: What is your added value?
AB  - In Part I of this series, I introduced the concept of memes (1). Memes are ideas
      or concepts--the information world equivalent of genes. The goal of this series
      of articles is to infect you with memes, so that you will assimilate, translate,
      and express them. No matter what our area of expertise or "-ology," we all are in
      the information business. Our goal is to be in the wisdom business. In the
      previous papers in this series, I showed that when we convert raw data into
      wisdom we are moving along a value chain. Each step in the chain adds a different
      amount of value to the final product: timely, relevant, accurate, and precise
      knowledge that can be applied to create the ultimate product in the value chain:
      wisdom. In Part II of this series, I introduced a set of memes for measuring the
      cost of adding value (2). In Part III of this series, I presented a new set of
      memes for measuring the added value of knowledge, i.e., intellectual capital (3).
      In Part IV of this series, I discussed practical knowledge management tools for
      measuring the value of people, structural, and customer capital (4). In Part V of
      this series, I will apply intellectual capital and knowledge management concepts
      at the individual level, to help answer a fundamental question: What is my added
      value?

PMID- 11299904
TI  - Managing knowledge workers in clinical systems.
AB  - In Future Work, Coates and colleagues cite seven forces that are reshaping work
      and the workforce. One is the advent of "knowledge workers," who gather,
      distribute, and add value to information. In health care, the transition to
      integrated delivery systems, replete with care plans, critical paths, and
      assessment of clinical outcomes supported by information technology, is driving
      the need to reeducate for a knowledge-based workforce. Managers of clinical
      systems need to be familiar with the characteristics of knowledge workers
      affecting the delivery environment, organizational structure, and culture of an
      organization. These same managers will be expected to develop strategies to
      manage the transition to a knowledge-based workforce.

PMID- 11299905
TI  - Calculating costs.

PMID- 11299906
TI  - Surviving staff reductions.

PMID- 11299907
TI  - Setting an example: are you keeping up with developments in your field?

PMID- 11299908
TI  - Sales skills for health-care professionals: the emotional side of sales.
AB  - Health-care sales continues to be an area of opportunity for many laboratory
      professionals. For those who possess the necessary skills and the desire to
      enthusiastically embrace the unique challenges of a sales career, a new CLMA
      publication by CLMR contributor Donna L. Nigon, MT(ASCP), titled Sales Skills for
      Health-Care Professionals, will provide the knowledge of sales structure and
      techniques needed to succeed. This Sales Skills excerpt, "The Emotional Side of
      Sales," describes many of the emotional aspects of sales and selling, including
      how to handle the transition from a technical or medical role to that of sales
      representative, relationship building, maintaining personal and professional
      support systems, dealing with rejection, avoiding burnout, time management, and
      customer concerns. For more information about this book, please see the order
      form that accompanies this excerpt, or visit www.clma.org.

PMID- 11299909
TI  - When an employee leaves: the effectiveness of clinician exit interviews and
      surveys.
AB  - As an organizational diagnostic tool, exit interviews or surveys (EIS) are a
      primary means of determining how exiting employees perceive strengths and
      weaknesses within the organization. This human resource management device should
      be evaluated, as any other, to determine effectiveness. In this article, various
      issues in assessing satisfaction with EIS are examined. Suggestions are made for
      improving organizational satisfaction with the EIS in health-care settings.

PMID- 11299910
TI  - Utilization management and information technology: adapting to the new era.
AB  - Overuse of clinical laboratory services has been written about for many years
      (1), but remedies that easily could be implemented and effective over the long
      term have been in short supply. This issue has been acute for CLS, Inc., which is
      wholly owned by a managed care organization (HIP Health Plan of New York).
      Because CLS is assessing the possibility of acquiring a new laboratory
      information system, we reviewed past reports on approaches to utilization
      management (UM) and considered how developments in information technology (IT)
      may affect the latter. We feel there is a distinct possibility for implementation
      of UM in real time, and we propose this as a new paradigm whose realization has
      implications for choice of IT and for how clinical laboratories operate in the
      future.

PMID- 11299911
TI  - Virtual automation.
AB  - Total laboratory automation (TLA) can be substituted in mid-size laboratories by
      a computer sample workflow control (virtual automation). Such a solution has been
      implemented in our laboratory using PSM, software developed in cooperation with
      Roche Diagnostics (Barcelona, Spain), to this purpose. This software is connected
      to the online analyzers and to the laboratory information system and is able to
      control and direct the samples working as an intermediate station. The only
      difference with TLA is the replacement of transport belts by personnel of the
      laboratory. The implementation of this virtual automation system has allowed us
      the achievement of the main advantages of TLA: workload increase (64%) with
      reduction in the cost per test (43%), significant reduction in the number of
      biochemistry primary tubes (from 8 to 2), less aliquoting (from 600 to 100
      samples/day), automation of functional testing, drastic reduction of
      preanalytical errors (from 11.7 to 0.4% of the tubes) and better total response
      time for both inpatients (from up to 48 hours to up to 4 hours) and outpatients
      (from up to 10 days to up to 48 hours). As an additional advantage, virtual
      automation could be implemented without hardware investment and significant
      headcount reduction (15% in our lab).

PMID- 11299912
TI  - Rebuilding morale after downsizing.
AB  - Motivating employees is one of a manager's most important roles, but it is a
      challenge in today's shifting health-care market. Decreasing funding and a
      changing patient population are forcing hospitals to either cut costs or go out
      of business. In such a tense environment, the possibility of layoffs continually
      looms over our heads. Whether your laboratory is contemplating job cuts or you
      already have been through them, you know there is no worse threat to employee
      morale. A March 1996 Strategic Management survey reported that poor morale is the
      worst human resource problem among 81% of 691 U.S. hospitals. Ronald Henkoff said
      it best in the January 1994 issue of Fortune Magazine: "A distressing 80% of
      downsizers admit that the morale of the remaining employees has been mugged.
      These sullen, dispirited, hunkered-down folks, lest we forget, are the very
      people who are supposed to revitalize our enterprise and delight our customers."
      Many times, when we focus on cost constraints and customer service, we overlook
      what we might do to improve trust among our staff. Rather than letting bad
      feelings run their course after 1999 job cuts, we decided to intervene. We
      developed new management tools and recovery interventions at Children's Medical
      Center to ward off discontent after the changes.

PMID- 11299914
TI  - HIPAA, HIPAA, hurrah! A chance to achieve efficiencies sooner rather than later.

PMID- 11299913
TI  - Washington Clinical Laboratory Initiative: a vision for collaboration and
      strategic planning for an integrated laboratory system.
AB  - This article addresses the importance of public health, hospital, and clinical
      laboratories in the role of patient care, disease prevention, and surveillance.
      It also focuses on the coordination and planning that needs to take place between
      these institutions in order to develop a more cost-effective and responsive
      laboratory delivery system. The Washington Clinical Laboratory Initiative is an
      innovative state initiative illustrating that coordinated and integrated
      strategic planning of public and private sector laboratories can be accomplished
      within a state. It also has increased interaction, collaboration, and
      communication between health practitioners, health plans, hospitals,
      laboratories, government agencies, and academicians. This accomplishment has
      enabled the establishment of public policy concerning laboratory reimbursement
      and development of standards of laboratory practice.

PMID- 11299915
TI  - Evolution of best practice.

PMID- 11299916
TI  - 100 top hospitals. Getting wired.

PMID- 11299917
TI  - GM and DM--a winning team.

PMID- 11299918
TI  - Fight illness with information.

PMID- 11299919
TI  - Promises to keep.

PMID- 11299920
TI  - One team's journey into wireless.

PMID- 11299921
TI  - From gee-whiz to must-have.

PMID- 11299922
TI  - Caring for healthcare.

PMID- 11299923
TI  - Take-home lessons.

PMID- 11299924
TI  - Unlocking the power of your EMPI.

PMID- 11299925
TI  - Standards of practice for nursing informatics.

PMID- 11299926
TI  - What works. Productivity minus paper.

PMID- 11299927
TI  - Decision support hotlist.

PMID- 11299928
TI  - Evolution and revolution in the practice of medicine.

PMID- 11299929
TI  - Why can't Dr. Johnny lead? Cultivating shared physician leadership.

PMID- 11299930
TI  - A holiday gift from Health & Human Services: final HIPAA privacy regulations
      contain significant changes.

PMID- 11299931
TI  - Cardiology trends 2001: reimbursement and cost reduction strategies.
AB  - In summary, the profitability of many cardiology programs across the country has
      declined due to changes in reimbursement, practice patterns and new technology.
      Hospitals are being challenged to find ways to improve reimbursement and reduce
      cost without compromising quality of care. These goals can be accomplished by
      analyzing service line specific data to identify opportunities to partner with
      physicians to provide high quality, low cost care.

PMID- 11299933
TI  - Will consumerism lead to more price-sensitive patients?

PMID- 11299932
TI  - A pharmacoeconomic evaluation of amlodipine usage in patients undergoing PTCA in
      the US using results from the Coronary Angioplasty Amlodipine Restenosis Study
      (CAPARES).

PMID- 11299934
TI  - Creating a sustainable physician compensation plan. Serving both fee-for-service
      and capitated populations.
AB  - A large, integrated health system in St. Louis acquired a primary care, health
      maintenance organization staff model group practice with 55 physicians. Health
      system leadership positioned the acquired physician group to diversify and expand
      its fee-for-service patient base to increase revenue and support the expansive
      fixed cost structure of the health centers. With interim managers, the leaders
      developed a new physician compensation plan that put a greater portion of the
      physicians' compensation at risk and provided incentives for enhanced
      productivity in both the capitated and fee-for-service lines of business. This
      article explores the key characteristics, benefits and potential areas for
      improvement associated with the new incentive compensation model and describes
      the centers' improved operating performance and gains in physician productivity.

PMID- 11299935
TI  - Physician group practice turnaround. Focus on physician behavior.
AB  - Physician behavior is an important driver in a group practice turnaround. A
      strong leadership team, giving physicians ownership, governance and proper
      incentives, creates the necessary behavior changes. It's also critical to have
      budget discipline, identify and make the hard decisions, provide effective care
      management, employ a sound business infrastructure and good contracting, and
      attend to physician morale.

PMID- 11299936
TI  - Can academic group practices survive in managed care environments?
AB  - Managed care environments have proven difficult for most health care
      organizations. Academic medical group practices--also called faculty practice
      plans--in particular have faced enormous challenges in making strategic
      adaptations to rapidly evolving health care markets. Recent evidence suggests
      that academic practices have been less than successful in implementing strategies
      focused on cost leadership and affiliations with primary care physicians. This
      article asserts that academic group practices cannot succeed by copying
      strategies implemented by other medical group practices because they have
      dissimilar missions, organizational capabilities and environmental constraints.
      The authors use the TOWS matrix--an acronym for threats, opportunities,
      weaknesses and strengths--a decision analysis framework that integrates both
      organizational and environmental factors, to assist executives in strategically
      positioning academic group practices.

PMID- 11299937
TI  - Case study: unionization of a newly acquired satellite practice.
AB  - In March 1997, a 24-physician primary care medical group in upstate New York
      acquired an occupational medicine practice. Shortly after the merger, motivated
      primarily by job security concerns, the employees of the occupational medicine
      group voted to unionize for the purpose of collective bargaining. The author--the
      practice manager for the merged medical group--describes the events that ensued
      as practice management and union employees struggled toward an agreement.

PMID- 11299939
TI  - Dot-com meltdown.

PMID- 11299938
TI  - Stop playing pinball with your patients.

PMID- 11299940
TI  - Banned in Boston. Medical mercury is on the way out.

PMID- 11299942
TI  - On the lookout! Employee safety means seeing beyond OSHA regs.

PMID- 11299941
TI  - A quest for the obscure.

PMID- 11299943
TI  - The costly price of splash exposures.

PMID- 11299944
TI  - What price patient privacy? HIPAA compliance hits hospital budgets hard.

PMID- 11299945
TI  - Stats. Declining health care costs (the headline you never thought you'd see).

PMID- 11299946
TI  - No agreement on nurse staffing.

PMID- 11299947
TI  - WellPoint to absorb Blues plan. Georgia insurance official approves acquisition,
      ending three-year battle.

PMID- 11299948
TI  - Transplant trouble. Program throttled by lack of organs; HHS in national bid to
      tout donations.

PMID- 11299949
TI  - United we do quite well, thank you. Survey: physicians say practicing in groups
      is a better way to provide care.

PMID- 11299950
TI  - Soft landing. PMH exec may benefit from takeover strategy.

PMID- 11299951
TI  - Headin to court. Bankruptcy court, that is, the new route even for big hospitals
      burdened by big bills.

PMID- 11299952
TI  - Walking the walk. IRS seeks proof of charity care at not-for-profits.

PMID- 11299953
TI  - The magic potion. Three bipartisan bills could be part of chemistry to reduce the
      number of uninsured.

PMID- 11299954
TI  - Do you know this company? Troubled firms try new names, but proof of change will
      come from behavior.

PMID- 11299956
TI  - Web survey. February survey results: alternative medicine.

PMID- 11299955
TI  - The rough and tumble of it. Hospitals flexing their muscles in contract disputes
      with insurers.

PMID- 11299957
TI  - Roots of trouble run deep. U.S. alleges Medicare fraud started in 1987; HCA says
      charges are 'nothing new'.

PMID- 11299959
TI  - Checkmate. Computer 'second reads' of mammograms get a lift from Congress.

PMID- 11299958
TI  - Trash talk. A scanner recovers surgical instruments workers so casually toss
      away.

PMID- 11299960
TI  - The conversion blues. Groups at odds over proceeds from Wis. Blues' change to for
      profit status.

PMID- 11299961
TI  - Comments flood HHS. Hospital groups push for further delay of patient-privacy
      regulations.

PMID- 11299962
TI  - Endometrial receptivity: changes in cell-surface morphology.
AB  - Ovulation and fertilization trigger embryonic development and endometrial
      differentiation by corpus luteum progesterone production. These two synchronous
      processes couple about 1 week later, when the blastocyst begins to implant in the
      now receptive endometrium (implantation window). Receptivity is a state of
      endometrial differentiation marked by a change in epithelial morphology: the
      hairy-like cell microvilli fuse to a single flower-like membrane projection
      called the "pinopode." Scanning electron microscopy of sequential endometrial
      biopsies shows that pinopodes form briefly (1-2 days), and their numbers
      correlate with implantation. On average, the formation of pinopodes is earlier in
      stimulated (days 19-20) and later in artificial (days 21-22) compared with
      natural cycles (days 20-21). There is, however, a wide (up to 5 days) variation
      between women in the cycle days on which pinopodes form. These results suggest
      the existence of a narrow and discrete implantation window in humans. Detection
      of pinopodes is a potential clinical marker to assess endometrial receptivity.

PMID- 11299963
TI  - Molecular interactions at the maternal-embryonic interface during the early phase
      of implantation.
AB  - In mammals the embryo must implant in the uterus and develop a placenta to gain
      nutrition and facilitate gas exchange. In this article, the earliest events in
      this process are reviewed. The embryo can implant only when it has reached the
      blastocyst stage. The blastocyst is composed of an inner clump of cells, the
      inner cell mass, that gives rise to the fetus and an outer layer of trophectoderm
      (TE), the precursor of the placenta. Both blastocyst and uterus must
      differentiate in parallel to reach the appropriate state of maturity (activated
      blastocyst and receptive uterus) at which implantation can occur. Interaction
      between TE and the luminal epithelium (LE) lining the uterus initiates
      implantation, and both soluble signals and association between molecules on
      apposed surfaces appear to be involved. A number of cell surface molecules have
      been implicated in the initial attachment between TE and LE. These include HSPG,
      Le-y and the H-type-1 antigen, HB-EGF, trophinin-tastin-bystin complex,
      integrins, and extracellular matrix molecules such as osteopontin and laminin.
      Others, such as mucins, may need to be removed or modified to allow adhesion to
      proceed. Evidence for the role of these components is discussed.

PMID- 11299964
TI  - Trophoblast-uterine interactions in the first days of implantation: models for
      the study of implantation events in the human.
AB  - The most profound changes in the relationship of the trophoblast to endometrial
      tissues occur in the first 5 days after the initiation of implantation. Not only
      have the earliest stages--adhesion and epithelial penetration--never been seen in
      the human, but also the trophoblastic plate and lacunar stages that follow are
      not available for modern investigative methods. Studies of appropriately timed
      endometrium and of trophoblast- and endometrium-derived cell lines have important
      implications for aspects of implantation. Use of nonhuman primates and other
      animal models for appropriate stages in implantation could further our
      understanding of direct trophoblast-uterine interactions. The mechanisms involved
      in epithelial penetration by infiltration of the syncytial trophoblast into the
      uterine luminal epithelium could be studied profitably using the marmoset or the
      ferret. Drawing of the blastocyst into an interstitial location might be
      investigated in the guinea pig. Formation of trophoblastic lacunae can be
      investigated in the cynomolgus monkey. By using such animal models of events of
      implantation in situ, implications concerning the molecules involved in adhesion,
      penetration of junctional complexes, and uterine vessel invasion that have been
      derived from in vitro or murine studies may be placed in context.

PMID- 11299965
TI  - Recent molecular approaches to elucidate the mechanism of embryo implantation:
      trophinin, bystin, and tastin as molecules involved in the initial attachment of
      blastocysts to the uterus in humans.
AB  - Elucidation of the implantation mechanism in humans at the molecular level has
      been difficult because of methodological restrictions. Instead of using human
      materials during the implantation period, two human tumor cell lines that
      respectively mimic the biological behaviors of a blastocyst and uterine luminal
      epithelial cells were utilized successfully to identify three novel adhesion
      molecules named trophinin, bystin, and tastin. Trophinin is a membrane protein
      strongly expressed both on the apical surface of the trophectoderm of a simian
      blastocyst and at a putative implantation site of the human endometrium. Bystin
      and tastin are cytoplasmic proteins that associate with trophinin by presumably
      forming an active adhesion machinery. The expression patterns of these molecules
      are suggestive of their involvement in the initial blastocyst attachment to the
      uterus as well as in the subsequent placental development. Future perspectives in
      molecular implantation research are also discussed in relation to breakthroughs
      in assisted reproduction.

PMID- 11299966
TI  - Intracellular signaling in the developing blastocyst as a consequence of the
      maternal-embryonic dialogue.
AB  - The success of blastocyst implantation is dependent on signaling between the
      embryo and the receptive endometrium. Intercellular signaling molecules, which
      include hormones, growth factors, and cytokines, have been identified that
      participate in the maternal-embryonic dialogue. These biologically active
      molecules may target uterine and/or embryonic tissues in a biochemical cascade
      that coordinates the two developmental programs during implantation. Two notable
      uterine products are calcitonin and heparin-binding epidermal growth factor-like
      growth factor, which are both expressed during the receptive phase of the
      endometrium in humans and in rodent models. We review data that demonstrate the
      ability of these molecules to accelerate blastocyst differentiation and delineate
      the respective intracellular signaling pathways that advance the embryonic
      developmental program. An understanding of the mediators regulating embryonic
      development in utero and their biochemical mechanisms of the action may provide
      insights for improvement of embryo culture in vitro prior to blastocyst transfer.

PMID- 11299967
TI  - Glycodelin: a pane in the implantation window.
AB  - Glycodelin is an endometrial protein with proposed immunomodulatory activity
      during human embryonic nidation. In this review we describe the effects of
      ovarian hormones on glycodelin transcription, synthesis, and secretion by human
      epithelial cells and focus on the importance of glycodelin in implantation. We
      demonstrate that glycodelin transcription, synthesis, and secretion by human
      epithelial cells are stimulated by progestins and antiprogestins but not by
      estrogen. Sequences localized within a 403-base-pair region flanking the 5' human
      glycodelin gene promoter appear to be responsible for transcriptional activation
      of this gene mediated by progesterone receptor-ligand complexes. Relaxin,
      purported to enhance glycodelin production in vivo and in prior in vitro studies,
      had no stimulatory effect on the expression of this gene in vitro in our models.

PMID- 11299968
TI  - Cytokines in implantation.
AB  - The endometrium of most species is now recognized as an important site of
      production of cytokines and their receptors. The cellular origin of the cytokines
      varies but many predominate in the uterine glandular or luminal epithelium or in
      the decidualized stromal cells. From studies in genetically modified mice it is
      clear that implantation of the blastocyst can proceed in the absence of most
      individual cytokines, although leukemia inhibitory factor and interleukin-11 have
      indisputable roles in this process. In other cases, such as CSF-1, GM-CSF, IL-1,
      and IL-6, the numbers of implantation sites or litter sizes are reduced when the
      cytokine is absent. The same cytokines that are implicated in implantation in
      mice are generally maximally expressed in human endometrium with maximal
      production in the secretory phase, particularly during the "window of
      implantation," but functional studies of their role in implantation in women and
      other primates are still required.

PMID- 11299969
TI  - Implantation in the human: the role of HOX genes.
AB  - HOX genes are transcription factors that are essential for the proper development
      of the mullerian tract in the embryonic period. It has been discovered that HOX
      genes are expressed in the adult uterus. Two of them, Hoxa10 and Hoxa11, have
      been demonstrated to be necessary for uterine receptivity and implantation in
      mice. Recent evidence also suggests such a role for HOX genes in humans. They are
      likely to be essential regulators of endometrial development in preparation for
      implantation. This article reviews the role of the HOX genes in the reproductive
      tract, their patterns of expression and regulation, the outcome of deficient HOX
      gene expression, and their potential mechanisms of action. The process of
      implantation is complex, and many molecular markers have been found expressed at
      high levels in the endometrium in the peri-implantation window. Targeted
      disruption has revealed that most of these molecules are redundant and not
      essential for implantation. The importance of Hox genes in this process has been
      well documented, and they remain one of the few well-characterized molecules
      necessary for implantation.

PMID- 11299970
TI  - The placenta dilemma.
AB  - Despite the critical role the placenta plays in governing the outcome of
      pregnancy, a great deal remains to be learned about this transient organ. Several
      factors have contributed to our relative lack of knowledge. For example, most of
      the placenta's development, which precedes that of the embryo or fetus, occurs
      during the first half of pregnancy in humans. Thus, it is difficult to obtain the
      tissue samples that are required to study relevant time points. In addition,
      placental anatomy is complex; one of the most interesting parts can be obtained
      only by biopsy of the uterine wall. Recent analyses of these biopsies, combined
      with information from cell culture models, revealed the unexpected finding that
      placental cells that invade the uterus phenocopy many endothelial cell
      characteristics. This finding has several interesting implications for normal
      pregnancy and for pregnancy complications that could be related, either directly
      or indirectly, to this phenomenon, such as preeclampsia and cytomegalovirus
      transmission.

PMID- 11299971
TI  - Acute necrotizing encephalopathy of childhood.
AB  - Symmetric change of the entire area of the bilateral thalami, as with panthalamic
      lesions, plus involvement of other regions in the brain rarely occurs to
      previously healthy children. The term, acute necrotizing encephalopathy of
      childhood, has recently been proposed. Its clinical, radiological, and
      pathological features are described. This disease predominantly affects infants
      and young children living in Taiwan and Japan, and manifests itself as acute
      encephalopathy following 2 to 4 days of fever and minor symptoms of the
      respiratory and/or gastrointestinal systems. The hallmark of this encephalopathy
      consists of multifocal, symmetric brain lesions affecting the bilateral thalami,
      and/or cerebral periventricular white matter, brainstem tegmentum, or cerebellar
      medulla, which can be documented by ultrasonography, computed tomography, and
      magnetic resonance imaging of the brain. The prognosis is usually poor. Less than
      10% of patients recover completely. Cases with good outcome were reported to have
      reversible imaging changes. Focal neurologic deficits are common sequelae. The
      pathogenesis of acute necrotizing encephalopathy of childhood is still not known.
      Some diseases, such as Reye's syndrome, vascular occlusion, tumor, hemorrhage of
      the thalamus, Sandhoff disease, or Leigh and Wernicke encephalopathies must be
      differentiated clinically, radiologically, or pathologically. By excluding other
      disease entities, acute necrotizing encephalopathy of childhood can be diagnosed.

PMID- 11299972
TI  - Hyperinsulinemia and insulin resistance related metabolic syndrome.
AB  - BACKGROUND: A cross-sectional study in northern Taiwan was conducted to
      investigate the role of serum insulin level on the development of hyperglycemia,
      hypertension, obesity and hyperlipidemia. METHODS: Demographic data (age,
      gender), body mass index, blood pressure, and laboratory blood tests (uric acid,
      total cholesterol, triglycerides, glucose and immunoreactive insulin when fasting
      and two hours after loading 75 gm glucose) were collected. A logistic model or
      polychotomous model, treating each chronic disease (hyperglycemia, hypertension,
      obesity and hyperlipidemia) as a dependent variable, were fitted to study the
      effect of serum insulin level. RESULTS: Four hundred and twenty one volunteers
      (women:men = 237:184) were recruited from 1991 to 1993. Women were more obese and
      had more hyperglycemia, while the frequency of hyperuricemia was lower than of
      men. Women with a higher level of the sum of fasting and 2-hour post glucose load
      insulin (SIRI) levels had higher frequencies of glucose intolerance,
      hypertension, obesity and hyperlipidemia, whereas SIRI was related to only
      obesity and hyperlipidemia in men. The high plasma SIRI was a risk factor for
      both impaired glucose tolerance (IGT) and obesity in women. Men with a high
      plasma SIRI showed a more than three-fold risk of obesity. CONCLUSIONS: We have
      observed that a higher serum insulin level was significantly associated with the
      development of metabolic manifestations (glycemic status and obesity) in a
      suburban community in northern Taiwan. Men and women with a higher serum insulin
      level probably had a greater chance of developing obesity, and women had a
      greater chance of developing IGT.

PMID- 11299973
TI  - Keratometric astigmatism after cataract surgery using small self-sealing scleral
      incision.
AB  - BACKGROUND: To evaluate the corneal refractive changes after a small self-sealing
      scleral wound. METHODS: A 4 mm self-sealing scleral tunnel incision and
      implantation of a foldable intraocular lens were adopted during
      phacoemulsification. A retrospective review of 48 consecutive isolated eyes in 48
      patients was performed to assess the postoperative corneal refractive change.
      Keratometric readings were recorded for 3 months following surgery. RESULTS: At
      one week postoperatively there was a -0.29 +/- 1.02 (standard deviation) change
      of Naeser's polar value (against-the-rule shift) in the cylinder keratometry. The
      cylinder had with-the-rule shift and recovered to the preoperative state at one
      month postoperatively. The change of Naeser's polar value at the third
      postoperative month was 0.05 +/- 0.80 (with-the-rule shift) compared with the
      preoperative polar value. The change of astigmatism at the third postoperative
      month was -0.38 +/- 0.74 (Diopters) using simple subtraction and -1.01 +/- 0.58
      (Diopters) using the Jaffe vector analysis. The axis of astigmatism exhibited a
      mild against-the-wound shift at 1 week and a gradual with-the-wound shift
      afterwards. CONCLUSION: The low induced astigmatism, early recovery of corneal
      curvature and no direct damage to the cornea support the concept and justify the
      use of a small self-sealing scleral tunnel incision during cataract surgery.

PMID- 11299974
TI  - Clinical features and outcome of appendicitis in children younger than three
      years of age.
AB  - BACKGROUND: Acute appendicitis is the most common surgically amenable cause of
      acute abdominal pain in children. We analyzed our past experience of
      appendectomies in children and present the clinical characteristics of
      appendicitis in children younger than 3 years of age. A better understanding of
      appendicitis in early childhood would allow us to achieve an earlier diagnosis.
      METHODS: A group of 475 children from 4 months to 15 years of age who underwent
      appendectomy for appendicitis was studied over a 5-year period from July 1994 to
      June 1999. Excluding cases with negative pathological findings (n = 34), they
      were divided into 2 age groups: group I (< or = 3 years old) and group II (> 3
      years old). Medical records were reviewed and comparisons between clinical
      findings, laboratory data, pathology findings, and complications were made.
      RESULTS: Of 441 cases enrolled in our study, 24 (5.4%) were 3 years of age or
      younger. Of all children older than 3 years of age, 32 (7.1%) had negative
      pathological findings compared to children younger than 3 years of age (7.7%).
      The duration of symptoms prior to diagnosis in group I was 3.6 days compared to
      group II at 2.0 days. Children from group I frequently showed a higher incidence
      of fever (90% vs. 53.4%), abdominal distention (50% vs. 9.8%), perforation (50%
      vs. 40.1%), and missed first impression (29% vs. 2.4%) than those from group II.
      Children of group I also had a higher complication rate (41.7% vs. 11.5%).
      CONCLUSIONS: In early childhood the symptoms and signs of appendicitis usually
      are nonspecific. There is a longer duration before diagnosis, more instances of
      fever and abdominal distention, less right lower quadrant pain, less local
      tenderness and rebounding pain, and no obturator sign. Close observation and on
      going evaluation of patients are essential.

PMID- 11299975
TI  - Predictors of readmission to a medical-psychiatric unit among patients with minor
      mental disorders.
AB  - BACKGROUND: Most studies on readmission have focused on patients with severe
      mental disorders such as schizophrenia and subjects were mostly collected in
      traditional psychiatric settings. This study investigated the predictors of
      readmission to a medical-psychiatric unit among patients with minor mental
      disorders in a general hospital. METHODS: All 164 patients admitted to a stress
      ward within a one-year period were recruited into this study. Data were
      retrospectively obtained by reviewing medical charts. Variables used to analyze
      and compare between patients who were and were not readmitted included patient
      characteristics, clinical features and multiple axes diagnoses of DSM-IV.
      RESULTS: Of 164 patients recruited, 135 were hospitalized only one time. The
      remaining 29 patients accounted for 61 admissions. The readmission rate was 17.7%
      (29/164). The significant predictors for readmission included Global Assessment
      of Functioning scores lower than 50 at admission, age under 40 years, previous
      psychiatric admission, alcohol dependence/abuse, dysthymia and comorbidity of
      borderline personality disorder. Using logistic regression to predict readmission
      within one year, we found the first four variables accurately differentiated
      84.15% of patients who were readmitted from those who were not. CONCLUSIONS: Our
      results indicated the incidence of relapse in certain minor mental disorders is
      similar to that of severe mental disorders. By identifying predictors of
      readmission and intervening appropriately, unnecessary readmission may be
      prevented.

PMID- 11299976
TI  - Effects of fluoride chewing gum on stimulated salivary flow rate and fluoride
      content.
AB  - BACKGROUND: The purposes of this study were to measure the stimulated salivary
      flow rates generated by sorbitol gum, fluoride gum and paraffin wax control, and
      to assess the salivary fluoride clearance pattern in fluoride chewing gum.
      METHOD: Six healthy subjects were instructed to chew paraffin wax control and
      sorbitol gum and fluoride gum (0.1 mg F/stick) 5 times per day for the
      experimental periods--21 days. Stimulated saliva samples were collected for each
      subject at 7, 14, 21 days at 3 pm after chewing of the gum. The saliva was
      collected at 1, 3, 5, and 8 minutes after the subject started chewing the wax or
      gum. Flow rates for each group and salivary fluoride content of the fluoride
      chewing gum were measured. RESULTS: The overall mean salivary flow rates for the
      control, sorbitol gum and fluoride gum were 1.7 +/- 0.6, 2.0 +/- 0.6, and 2.1 +/-
      0.7 ml/min respectively. The mean stimulated flow rate for fluoride gum was found
      significantly higher than that of the control (p = 0.002). However, no
      significant differences appeared between the control and sorbitol gum (p =
      0.104), and sorbitol gum and fluoride gum (p = 0.563). The mean fluoride
      concentrations at different intervals during eight minutes of chewing fluoride
      gum were between 1.8 and 4.2 ppm. CONCLUSION: Chewing fluoride-containing chewing
      gum releases fluoride at a low concentration in saliva. Fluoride chewing gum
      combining a salivary stimulator and caries prevention agent is a perspective
      method of caries prevention.

PMID- 11299977
TI  - Acute jejunogastric intussusception: report of five cases.
AB  - The purpose of this study was to investigate the clinical manifestations and
      diagnosis of patients with acute jejunogastric intussusception. From May 1986 to
      June 1999, a total of 5 men (54-76 years old) were collected. Their initial
      presentations included epigastralgia (4), coffee-ground vomitus (3), frank
      hematemesis (1), and tarry stool (1). All patients had gastric surgeries 10-30
      years previously. Radiograph of the abdomen showed a soft tissue density at the
      left upper quadrant in one patient. Panendoscopies were done in 4 patients. An
      obstructed efferent loop with a distended hyperemic small bowel protruding into
      the remnant of stomach was found in 3 cases, gangrenous change of the bowel wall
      in one of them. Stump cancer was diagnosed initially in the other patient. Barium
      study (3/5) showed efferent loop obstruction with "coil spring sing" and a
      central defect in the stomach. All 5 patients underwent segmental resection and
      end-to-end anastomosis between the 2nd to 6th hospital day. Operative findings
      were type II jejunogastric intussusception with retrograde invagination of a
      segment of efferent loop (30-100 cm in length) into the stomach. In conclusion,
      acute jejunogastric intussusception is an emergent condition. Early and accurate
      diagnosis is important. A high susception must be kept in mind in patients having
      a history of gastrojejunostomy with severe abdominal pain or upper
      gastrointestinal bleeding.

PMID- 11299978
TI  - Prenatal diagnosis of persistent fetal bradycardia: report of four cases.
AB  - Persistent fetal bradycardia is infrequent in prenatal life and difficult to
      manage optimally. It is generally attributable to sinus bradycardia due to fetal
      distress, blocked atrial extrasystoles, and congenital complete heart block. We
      reported four cases of persistent fetal bradycardia from 1995 to 1999 in our
      hospital. The first, second, and third cases of sustained fetal bradycardia had
      congenital complete heart block with positive titers for anti-Ro/SSA antibodies
      in both mothers and fetuses. Because of progressive fetal hydrops in the second
      case, the pregnancy was terminated. The first and third cases were isolated
      congenital complete heart block without structural anomaly. After prenatal
      examination the babies were followed up closely until term and both had a good
      prognosis without any implantation of pacemaker. In the fourth case there was no
      clinically known etiology associated with sustained fetal bradycardia. The fetal
      heart rate returned to normal after 6 weeks of follow-up and the baby was
      delivered without any cardiac problems. Congenital complete heart block is the
      most common cause of persistent fetal bradycardia. Prenatal detailed monitoring
      until delivery is necessary before heart failure develops. Treatment strategies
      (corticosteroids, ritodrine, and plasmapheresis) are debatable and may include
      prophylactic therapy for high-risk pregnant women.

PMID- 11299979
TI  - Pyeloureteritis cystica: case report.
AB  - Pyeloureteritis cystica, characterized by multiple bubbly filling defects on
      urography and caused by inflammatory stimuli, is a rare disorder of the ureter.
      It commonly affects older people. Diagnosis is established by radiological
      studies. Antibiotics should be given if urinary tract infection is present. Up to
      now, no other specific treatment can be used to cure this disorder. We report a
      case of pyeloureteritis cystica associated with urinary tract infection and a
      ureteral stone in a young woman who presented with hematuria and bilateral flank
      pain. The pyeloureteritis cystica had a bead-like appearance on intravenous
      pyelogram and retrograde pyelogram as well as in magnetic resonance urography.
      The diagnosis and treatment of this disorder are discussed. Magnetic resonance
      urography can provide high-resolution of coronal images of the entire urinary
      tract without the use of contrast agents or ionizing radiation. However, the cost
      of the procedure is a major concern.

PMID- 11299980
TI  - Pancreatitis with gallbladder ascariasis in a child: case report.
AB  - A 10-year-old girl was admitted for abdominal pain for 1 week. Morning vomiting
      with 5 Ascaris and diarrhea with Ascaris were found. Radiograph of the abdomen
      disclosed no significant abnormality. Abdominal sonogram revealed a normal
      biliary tree; but mildly enlarged pancreatic thickness, and thickened gallbladder
      wall. Within the thickened gallbladder wall a linear echogenic structure with
      worm-like movement suspected of being Ascaris was found. We report this case
      because pediatric pancreatitis and a gallbladder wall thickened with worm
      movement have rarely been reported. Urgent treatment and surgery are required for
      the very ill child with a tensely distended abdomen or signs of peritoneal
      irritation. Early diagnosis is very important to prevent further complications.
      We emphasize the role of sonography in the diagnosis of this case and the
      prevention of progressive deterioration.

PMID- 11299981
TI  - Clinical pathways set to experience 'technological rebirth'.
AB  - The state of the art in case management care plans is automation. Larger hospital
      systems are at the beginning of a technological rebirth, and that includes acute
      care clinical pathways, according to case managers at New York University Medical
      Center in New York City and Emory University Hospital in Atlanta. Despite some
      minor glitches, and the perennial issue of getting physician support for
      pathways, the systems are up and running. Users are hopeful that pathway
      technology will continue to improve and someday be linked electronically to
      outcomes software.

PMID- 11299982
TI  - How to build a pathway program from scratch.
AB  - Starting a pathway program from the ground up requires specific building blocks
      and certain personality traits: persistence, flexibility, and the ability to work
      with others. Carol Freeborn, RN, started a pathway program in the early 1990s at
      Mercy Hospital in Toledo, OH. She shares her experience and advice for others who
      are starting pathway programs in their own facilities.

PMID- 11299983
TI  - CM cooperation skills help doctors to 'buy in'.
AB  - Physicians play a key role in making your care pathways successful, says Maria
      Brillant, RN, coordinator of case management at NYU Medical Center. Case managers
      at her facility have a philosophy of cooperation that encourages the right
      doctors to champion the right pathways. Using a step-by-step pathway for getting
      buy-in can help case managers and physicians foster cooperation.

PMID- 11299984
TI  - Pediatric simple open heart surgery critical pathway.
AB  - In 1997, administrators discovered that DRG 108 (other major cardiothoracic
      procedures), which includes many of the surgical repairs for congenital heart
      disease, was one of the biggest money losers for Vanderbilt Children's Hospital,
      resulting in a loss of approximately $1 million dollars per year. Time for
      action.

PMID- 11299985
TI  - Initiative cuts ED visits, hospital admissions.
AB  - When Sutter Health Central in Sacramento, CA, got involved in managed care and
      global capitation several years ago, it made sense to identify the patients
      likely to use the system a lot and do interventions to prevent them from getting
      to that point, says Jan Van der Mei, RN, continuum case management director.

PMID- 11299986
TI  - Referrals ensure continuum of care.

PMID- 11299987
TI  - Enhance pathways to make patient central focus.
AB  - With the use of electronic pathway software, case managers at Vanderbilt
      University Medical Center in Nashville, TN, have been able to add unique order
      sets to their standard diagnosis pathways, says Irene Hatcher, MSN, RNC,
      coordinator of case management and clinical pathway development. "A nursing
      diagnosis of 'spiritual distress' is rarely, if ever, seen on a care plan, even
      though it may be the most frequently seen problem," she says in a report on the
      subject. Her facility has begun including spiritual needs order sets to its
      pathways.

PMID- 11299988
TI  - JCAHO patient safety standards stress leadership.

PMID- 11299989
TI  - Medication study may bolster compliance.

PMID- 11299990
TI  - Personal fortune. Would you like cheese with that?

PMID- 11299991
TI  - If you're feeling a little pinched....

PMID- 11299992
TI  - The winds of change.

PMID- 11299993
TI  - Losing sight of HIV prevention.

PMID- 11299994
TI  - Breakfast with Laurie. Interview by Bob Roehr.

PMID- 11299997
TI  - The financial manager's role in preventing medical errors.

PMID- 11299996
TI  - Shifty fat and bad bones (or, in vivo veritas).

PMID- 11299995
TI  - Historic IAPAC event honors AIDS pioneers.

PMID- 11299998
TI  - Will President Bush keep his promises?

PMID- 11299999
TI  - Penton: strong expense controls, good clinical outcomes mean success.

PMID- 11300000
TI  - Merger failure: a five-year journey examined.
AB  - In 1994, Catholic Medical Center and Elliot Hospital in Manchester, New
      Hampshire, merged to form Optima Health, a full-ownership, not-for-profit IDS.
      Initially, Optima Health was an economic success. A number of strategic
      miscalculations, however, led to the IDS's demise. First, Optima Health's leaders
      failed to fully consider the divergent cultures of the two hospitals,
      particularly with respect to their religious differences. Second, Optima Health's
      leaders did not anticipate the public's response to the organization's
      consolidation plan. And third, the consolidation was found to have changed the
      charitable missions of the two tax-exempt hospitals in violation of Federal laws
      regarding charitable trusts. The issues combined to undermine the commitment of
      the organization's leaders to the consolidation strategy, and Optima Health was
      dissolved.

PMID- 11300001
TI  - Capitation: a strategy that could have a future.
AB  - Capitation can be successful if hospitals, physicians, and payers share risk to
      align financial incentives to control costs. Payers need to help hospitals that
      accept risk to achieve success under managed care agreements. Many failures in
      hospital capitation might be preventable if hospitals improve internal operations
      and commit themselves to making the changes necessary for successful risk-based
      payment.

PMID- 11300002
TI  - The top ten pitfalls in managed care contracts.
AB  - Managed care contracts may contain clauses that either have no purpose or have a
      purpose that the provider does not fully understand. Such clauses may go
      unrecognized by providers until they are invoked by payers during a contract
      dispute, often to the detriment of providers. Providers should attempt to exclude
      or modify such clauses. Providers also should define basic concepts, such as
      identifying the terms of the contract, determining how disputes might arise over
      these terms, documenting the agreement struck with the payer, selecting an
      appropriate dispute-resolution mechanism, and developing a strategy for speedy
      dispute resolution.

PMID- 11300003
TI  - Strategies for navigating the healthcare credit market.
AB  - Not-for-profit healthcare organizations are experiencing a tightened credit
      market due to financial stresses on the healthcare industry such as declining
      payments, effects of the Balanced Budget Act of 1997, and the shift to outpatient
      care. In the future, healthcare organizations wanting to access the capital
      market will be expected to preserve cash as an "insurance policy," offer greater
      security and stricter covenants, and report financial information on a quarterly
      basis. To meet these requirements and navigate today's tighter credit market,
      healthcare financial managers will need to focus on the organization's most
      reliably profitable areas of business, link strategic and financial issues, and
      carefully monitor the balance sheet.

PMID- 11300004
TI  - HIPAA standards offer more accuracy and eventual cost savings.
AB  - More than four years after passage of the Health Insurance Portability and
      Accountability Act (HIPAA), HHS has yet to issue final rules regarding
      implementation of many of the statute's provisions. Of immediate concern to the
      healthcare industry are the final rules regarding electronic transactions and
      privacy and the proposed rule regarding security. The electronic transactions
      final rule addresses seven transaction types covered by HIPAA. The final rule
      mandates the use of standard implementation guides developed by the American
      National Standards Institute and specifies which code sets are to be used with
      each type of transaction. Under the security proposed rule, covered entities
      would be required to develop a security plan addressing four specific areas.
      Under the privacy final rule, covered entities must meet specific requirements
      regarding patients rights, including obtaining consent or, in some instances,
      authorization to use and disclose patients' personal health information.

PMID- 11300005
TI  - Cost segregation of assets offers tax benefits.
AB  - A cost-segregation study is an asset-reclassification strategy that accelerates
      tax-depreciation deductions. By using this strategy, healthcare facility owners
      can lower their current income-tax liability and increase current cash flow.
      Simply put, certain real estate is reclassified from long-lived real property to
      shorter-lived personal property for depreciation purposes. Depreciation
      deductions for the personal property then can be greatly accelerated, thereby
      producing greater present-value tax savings. An analysis of costs can be
      conducted from either detailed construction records, when such records are
      available, or by using qualified appraisers, architects, or engineers to perform
      the allocation analysis.

PMID- 11300006
TI  - Court rules EMTALA covers patients not physically on a hospital campus.

PMID- 11300007
TI  - ASC X12 standards improve claims tracking.

PMID- 11300008
TI  - Medical expenses can be a valuable income-tax deduction.

PMID- 11300009
TI  - HIPAA standardization signals new, streamlined PFS processes and organizational
      structure.

PMID- 11300010
TI  - Data trends. Hospital financial indicators continue to show little improvement.

PMID- 11300011
TI  - Molecular biology and the clinical management of patients with hereditary
      colorectal cancer syndromes.

PMID- 11300012
TI  - [Diagnostic strategies for the early detection of colorectal tumors: a critical
      analysis].

PMID- 11300013
TI  - [The value of endoscopy in the diagnosis of colorectal cancer].

PMID- 11300014
TI  - [Radiology in colorectal cancer].

PMID- 11300015
TI  - [Radioisotope technics in clinical staging of colorectal cancer].

PMID- 11300016
TI  - [Surgical treatment of rectal tumors].

PMID- 11300017
TI  - [New drugs in the therapy of colorectal cancer].

PMID- 11300018
TI  - [Combined therapy of rectal tumors: the chemotherapy].

PMID- 11300019
TI  - [Follow-up of radically resected colorectal cancer].

PMID- 11300020
TI  - [Follow-up in colorectal cancer].

PMID- 11300021
TI  - [Rational and methods of using antiemetics in the treatment of colorectal
      cancer].

PMID- 11300022
TI  - [Continuous versus intermittent infusion in chemotherapy of colorectal cancer].

PMID- 11300023
TI  - [Irinotecan in colorectal cancer].

PMID- 11300024
TI  - [Radiochemotherapy of rectal tumors].

PMID- 11300025
TI  - [Oxaliplatin in colorectal cancer].

PMID- 11300026
TI  - [Raltitrexed in colorectal cancer].

PMID- 11300027
TI  - [Capecitabine in the treatment of colorectal cancer].

PMID- 11300028
TI  - [New drugs for colorectal cancer: UFT].

PMID- 11300029
TI  - [Costs, disease management and DRG].

PMID- 11300030
TI  - Endpoints of medical treatment of colorectal cancer.

PMID- 11300031
TI  - [Surgical treatment of hepatic metastasis in colorectal cancer].

PMID- 11300032
TI  - [Percutaneous treatment: radiofrequency ablation of hepatic metastases in
      colorectal cancer].

PMID- 11300033
TI  - [Locoregional therapy in hepatic metastases of colorectal cancer].

PMID- 11300034
TI  - [Colorectal cancer: at the crossroads of histopathology and molecular pathology].

PMID- 11300035
TI  - [Phenotypic markers in colorectal cancer].

PMID- 11300036
TI  - [Molecular factors predictive of response to chemotherapy in advanced stages of
      colorectal cancer].

PMID- 11300037
TI  - [Functional tumor markers in colorectal cancer].

PMID- 11300038
TI  - [Colonic cancer. Adjuvant therapy: the Italian experience].

PMID- 11300039
TI  - Adjuvant therapy for colon cancer: the European experience.

PMID- 11300040
TI  - Adjuvant chemotherapy for colon cancer: the US experience.

PMID- 11300041
TI  - Novel agents in colorectal cancer.

PMID- 11300042
TI  - [Prematurity, network: focus in the year 2001].

PMID- 11300043
TI  - [Plasma insulin, IGF-I and breast cancer].
AB  - Several recent epidemiological studies have shown an increase in breast cancer
      risk among women who have elevated plasma levels of testosterone, reduced levels
      of sex hormone-binding globulin (SHBG), and hence elevated levels of bioavailable
      androgens and estrogens not bound to SHBG. This endocrine profile is generally
      associated with obesity and chronic hyperinsulinemia, of which it is most likely
      a result. Lack of physical activity, obesity, and a diet rich in rapidly
      digestible carbohydrates and poor in fibre favour the development of insulin
      resistance and hyperinsulinemia. The elevated insulin levels, in turn are related
      to decreases in plasma and tissue levels of IGFBP-1 and IGFBP-2 (insulin-like
      growth factor-binding proteins), and this may increase the availability of
      insulin-like growth factor-I (IGF-I) to its receptors. Like insulin, IGF-I also
      inhibits the hepatic synthesis of SHBG, whereas both hormones stimulate the
      ovarian synthesis of sex steroids. Moreover, insulin and IGF-I can both enhance
      the development of breast tumours, through their cognate receptors within the
      mammary tissue. Taken together, these observations lead to the hypothesis that
      breast cancer risk may be increased in women with elevated plasma insulin levels,
      and/or with elevated levels of bioactive IGF-I. Hyperinsulinemia and an increased
      IGF-I bioactivity could thus be an important physiological link between a western
      lifestyle, overnutrition, a hyperandrogenic sex steroid profile, and increased
      breast cancer risk. Prospective cohort studies will be needed to test this
      hypothesis, and to study in greater detail the possible relationships of breast
      cancer risk with plasma levels of IGF-I and IGFBPs. Confirmation of a
      relationship of breast cancer risk with plasma insulin levels, on the one hand,
      or with total plasma IGF-I, on the other hand, could open up new perspectives for
      breast cancer prevention, either by changes in dietary intake patterns and
      physical activity, or by the use of certain chemopreventive drugs.

PMID- 11300044
TI  - [Comparison of 2 therapeutic strategies in severe endometriosis, in young women
      consulting for sterility or pain. II. In the case of infertility, value of
      ovarian stimulation with intrauterine insemination after surgery].
AB  - AIM OF THE STUDY: Define the best medico surgical strategy in infertile women
      with stage III-IV endometriosis. MATERIAL AND METHODS: Two groups, A (N26) and B
      (N 37), treated for infertility associated or not with pelvic pain, due to stage
      AFS III or IV endometriosis, were compared. They had similar surgical procedure:
      operative laparoscopy including resection of endometriotic lesions, more
      particularly endometriomas and rectovaginal septum nodules. Associated medical
      strategy was different: group A, operative laparoscopy without preoperative
      treatment and in 40% a second laparoscopy taking place after 2-3 months of LHRH
      analogues; no post operative treatment; group B, operative laparoscopy taking
      place after ovarian blockage with 3-6 weeks of Diane (Androcur + ethinyl
      estradiol), then 2-3 months of analogue postoperative treatment immediately
      followed by ovarian stimulation (OS) + intrauterine insemination (IUI) in women
      more than 30 years old with operative tubes (N 22), no treatment for six months
      in similar cases less than 30 (N 5), and IVF in women with damaged tubes (N 5) or
      after OS + IUI failure (N 4). One patient refused two patients with high FSH
      level had oocyte donation. RESULTS: Two years evolutive pregnancy rate was
      significantly higher (p < 0.01) in group B (59%) versus group A (23%) and was
      higher after OS + IUI (68%) than after IVF (55%) or without any treatment in
      women < 30 (43%). The difference is equally significant by age (p < 0.05), for
      endometriomas (p < 0.01) and for recurrences (p < 0.01). CONCLUSION: Similar
      results obtained for pelvic pain (see chapter I) suggest that both strategies are
      similarly successful in treating endometriosis. These results confirm the
      interest of an ART after surgery for stage III-IV endometriosis and show that OS
      + IUI, a less costly than IVF technique, can be used successfully in selected
      cases with operative tubes.

PMID- 11300045
TI  - [Voluntary interruption of pregnancy: comparative study between 1982 and 1996 in
      the main center of Cote d'Or. Study of women having repeat voluntary interruption
      of pregnancy].
AB  - Since the egal use of induced abortion (1975), all the studies have shown a
      relative stability of the abortion rate related to delivery. Otherwise since 1985
      we have noted an increase of repeat abortions. OBJECTIVE: We compared in same
      center two populations of aborters with a fifteen year's interval. Then we
      analysed the psyco-social conditions of patients who had more than one abortion
      (R). METHODS: It was a comparative study between 1982 and 1996 in the main center
      of Cote d'Or (France). A representative sample of patients coming for abortion
      was retrospectively compared, (348 for 1982 and 343 for 1996). RESULTS: There
      were more not married patients (p = 0.0003), more nulliparous women (p = 0.0017)
      and more nulligestities' one (p = 0.03) in 1996 than 1982. The interval between
      the previous pregnancy and in 1996 (p = 0.03). Repeat abortions (R) represented
      15.8% in 1982 and 21.6% in 1996. Women who have had two or more abortions had
      increased significantly between 1982 (1.4%) and 1996 (5.2%) (p = 0.013). The R
      patients had more living children than patients who accessed for the first time
      at abortion (noR) in the two periods (p = 0.0003) and there were more women less
      thirty years old in the R group in 1996 than in 1992 (p < 0.05). The R mean age
      for the first abortion and for the first pregnancy were lower than the noR group
      in 1996: respectively 23.7 years versus 27.4% years (p = 0.00009) and 20.8 years
      versus 23.7 years (p = 0.0001). There were no significant difference between R
      and noR groups with regards of contraceptive failing, the reasons of abortion and
      the socio-professional categories. CONCLUSIONS: There were no difference in the
      number of abortion between 1982 and 1996. However we noted an increase of repeat
      abortion. This group was characterised by great socio-economic problems, unstable
      couples and ambivalence with wish of pregnancy and no wish of children. It seemed
      exist a real psycho-social precariousness. Actually, this population was
      perfectly aware of contraceptive methods.

PMID- 11300046
TI  - [Management of pregnant women infected with HIV at Bichat Hospital between 1990
      and 1998: analysis of 202 pregnancies].
AB  - OBJECTIVE: To describe medical and obstetrical prenatal care of pregnant women
      infected by HIV-1 emphasizing the role of cesarean section. DESIGN: A
      retrospective study of 202 pregnancies followed between 1990 and 1998 in a french
      hospital in Paris. RESULTS: 56.9% of the women were born in subsaharian Africa;
      80.2% were infected by sexual intercourse and the seropositivity was discovered
      during the pregnancy in 51% of the cases. Viral coinfections by hepatitis B
      virus, hepatitis C virus and Human papillomavirus were found respectively in
      14.7%, 16.5% and 13% of the pregnancies. Prematurity occurred in 15% of the
      deliveries. Efficacy of antiretroviral therapy was confirmed in this study: 5.7%
      of the children were infected despite the antiretrovial treatment versus 19.3%
      without treatment (p < 0.03). Prophylactic cesarean section was proposed to the
      patients since 1994; the morbidity of cesarean was 8.8% (69 cesarean sections).
      CONCLUSION: The policy of the association of prophylactic cesarean section and
      monotherapy by Zidovudine is validated by recent studies. The extension of
      prophylatic cesarean section to all the pregnant women infected by HIV is
      proposed. However the evaluation of the morbidity of the cesarean section in HIV
      infected women needs a prospective case-control study.

PMID- 11300047
TI  - [Parental sexuality and intimate relations of parental couples:
      conceptualizations of children aged 10 and 11 years].
AB  - This qualitative study explores the intimate relationship between parents as
      conceived by ten and 11 years old children. In a semi-structured interview and a
      semi-projective test, twelve children (6B/6G) were as to "imagine" the
      motivations that make parents want to be alone together. The content analysis of
      the children's stories showed at an affective level some indications of a: 1)
      capacity to recognize the exclusivity of the parental intimacy; 2) reluctance to
      recognize the sexual dimension of the parental intimacy. At a cognitive level,
      the content analysis indicates that 10 and 11 year old boys and girls have the
      capacity for decentralization, that is, to take the point of view of their
      parents. These results were discussed in light of the literature data.
      Educational implications were considered.

PMID- 11300048
TI  - [Chronic pelvic pain. Another diagnostic and therapeutic approach].
AB  - Chronic pelvic pain (CPP) is a frequent and difficult problem because despite the
      quality and diversity of diagnostic procedures no relevant etiology will be found
      in 30 to 40% of all cases. Psychologic and psychotherapeutic counselling is than
      usually proposed and usually not well accepted. A different approach can now be
      proposed according to a new semeiologic overall. In many cases the pain dominant
      is not visceral but parietal. The pelvic envelope is actually more painfull than
      the pelvic content. In these cases one can evoke the diagnosis of pelvic
      fibromyalgia and this is quite similar to classic fibromyalgia. This
      pelvifibromyalgia can be quantified with an algometric index. This form of pain
      actually is the somatisation of a past and difficult issue which will be very
      slowly and progressively revealed in the realm of a multidisciplinary and
      simultaneous physical and psychological approach. In the majority of cases these
      women have occurred physical, moral or sexual trauma inflicted by family members
      or a third party. Taking in account the physical dimension of body pain at the
      same time as psychotherapy will considerably enhance the efficiency of treatment.
      In our experience 70% of all women will be cured using this new approach.

PMID- 11300049
TI  - [Managing Varicella in the pregnant woman].

PMID- 11300050
TI  - [Breast magnetic resonance imaging and breast cancer].

PMID- 11300051
TI  - [ITwin pregnancy after treatment for infertility: failure or success? A failure].

PMID- 11300052
TI  - [Twin pregnancy after treatment for infertility: failure or success? A success].

PMID- 11300053
TI  - Resisting totalitarian responses to HIV.

PMID- 11300054
TI  - . . . a tapestry of women's experiences. XIII International AIDS Conference
      presents vital information about women and HIV/AIDS.

PMID- 11300055
TI  - Researchers struggle with complex nature of mother-to-child transmission of HIV.

PMID- 11300056
TI  - [Cholecystectomy with microlaparotomy and innovation of the ROMICRO R-set].
AB  - Gallstone disease is a major health problem, 10-15% of the adult population of
      Hungary are afflicted, and each year about 20,000 cholecystectomies are
      undertaken. There are two essential and widely accepted methods for the removal
      of gallbladder: conventional open cholecystectomy and laparoscopic
      cholecystectomy. Since 1988 the authors worked on a new surgical technique and
      equipment (ROMICRO R-set) for cholecystectomy using a single 2-4 cm
      microlaparotomy inside the infrasternal triangle. They demonstrate the
      innovation's phases of this new technique and ROMICRO R-set. Till 1999 more than
      7000 microlaparotomy cholecystectomy were undertaken in Hungary. The benefits of
      laparoscopic cholecystectomy can be achieved with less expense and risk by
      microlaparotomy cholecystectomy. Most patients are often not willing to accept
      conventional open cholecystectomy, but the microlaparotomy cholecystectomy
      alternative is unknown to the public and to most physicians. All countries have
      experienced a fast growth in their health care expenses over the last decades
      which will continue in the future. But spending an ever larger share of our
      nation's resources on health care cannot be afforded. As a consequence, making
      choices will became more and more unavoidable, also in galltree surgery.
      Therefore economic evaluation compares the different techniques of
      cholecystectomy necessary not only in terms on surgical and on patients aspect,
      but also in term of costs.

PMID- 11300057
TI  - [Technical difficulties of microlaparotomy for cholecystectomy].
AB  - Microlaparotomy cholecystectomy (MLC) is an alternative for minimal invasive
      surgical interventions of the biliary tract. In Hungary over 7000 operations were
      performed in 21 surgical departments as at December 31. 1998 and numerous
      additional departments have indicated their demand for the initiation of the
      method. Every new surgical procedure requires a "learning curve" during the
      application of MLC, difficulties encountered with the surgical solution occurred
      in a 14-15% range. We studied difficulties noticed during micro-, minilaparotomy
      cholecystectomy in 2400 unselected cases from the adoption of the surgical method
      in our department until December 31, 1998. We grouped our findings into
      avoidable, and unavoidable difficulties. Circumstances that can present
      unavoidable difficulties include: the patient's abnormal change in build,
      surgical interventions that have to be performed on patients 8-10 days after
      obstructive cholecystitis, abnormal gallbladder not indicated during preoperative
      examination, as well as biliary tract variations. A considerable part of the
      difficulties can be avoided by MLC-desirable positioning of the patient on the
      operating table, appropriate choice of surgical incision site and method,
      satisfactory anaesthesia, the use of necessary instruments suitable for exposure
      and unobjectionable illumination of the surgical area, as well as the performance
      of cholecystectomy with required modifications per given circumstances. The
      concomitant 2.5-16% alternating conversion rate after minicholecystectomy is
      indicative of the importance of the use of instruments assuring adequate exposure
      and excellent illumination of the surgical area. During the practice in our
      department this occurrence was recorded in 0.29% with the use of the ROMICRO R
      set.

PMID- 11300058
TI  - [Results of parathyroidectomy for primary hyperparathyroidism].
AB  - We have performed 16 operations on 14 patients with primary hyperparathyoidism
      caused by a solitary parathyroid adenoma in our department between 1st jan. 1990
      31 dec. 1999. In each case bilateral neck exploration was carried out. As in one
      case it was located in ectopic neck position, in the other case papillocarcinoma
      of the thyroid gland and ectopic parathyroid adenoma in mediastinal position were
      present, primary hyperparathyroidism persisted, so reoperation was needed.
      Histological examination proved the presence of adenomin all cases. Diffuse
      hyperplasia and parathyroid cancer did not occur. Before operation all patients
      underwent US and seven of them had radionuclide scintigraphy. CT scan aided in
      its localization with four patients. We did not make use of invasive methods,
      after the first operation 12 patients showed normal S-Ca levels very quickly. In
      two cases this level was too high after the operation and reoperation was
      necessary which resulted in normal Ca levels. Even though the number of our cases
      is rather modest, all the patients recovered. This may prove that we can
      successfully cure our patients of modern methods of diagnostics used for
      meticulous examination alongside with careful preparation of the patients by
      internal specialists are followed by the standard operative techniques available.

PMID- 11300059
TI  - [Local antibiotic treatment of chronic thoracic empyema].
AB  - The authors present their indications, aims and method for the local antibiotic
      treatment of chronic empyema thoracis. They analyse the sensitivity and resistant
      conditions of the most often occurring bacteria, Pseudomonas spp., in an open
      window treatment of empyema thoracis. 338 patients were treated for intrathoracic
      suppuration between January 1, 1987 and December 31, 1998. The youngest patient
      was 13, the oldest one was 90 (the average age was 53.2. Of these 11 died,
      representing a mortality rate of 3.2%. Of these 11 patients, 7 suffered from
      chronic intrathoracal suppuration. 82 patients had chronic empyema. 44 patients
      (13%) were treated by the open window procedure, 6 females and 38 males. The
      average age was 62.1. Of them 7 died, the mortality rate of chronic empyema
      thoracis was 8.5% in our department. Of 164 pus samples taken from suppurative
      pleura cavity bacteria, Pseudomonas spp., were bred in 148 cases during
      bacteriological examinations. Their bacteriological examinations confirm that
      local and aimed treatment by Polimyxin, Amikacin, Meronpenem, Ceftadizim,
      Imipenem, Tobramycin, Ciprofloxacin and Piperacillin proved to be the better
      medicine against Pseudomonas infection.

PMID- 11300060
TI  - [Regional chemotherapy in thoracic surgery].
AB  - The authors introduce their experiences on intracavital chemotherapy of mainly
      secondary pleural and pericardial malignant effusions based on a 5 years term of
      routinely used practise. In the cases of patients proper to the indicational
      conditions palliative regional cytostatic treatment was applied through
      transthoracal and intraopericardial (inserted by modified Fontenelle method)
      drains in order to cessate definitively the exsudation to improve the quality of
      life.

PMID- 11300061
TI  - [Primary manifestation of monophasic synovial sarcoma in the lung].
AB  - The authors introduce a case of a 41 years old male patient who was examined
      first on pulmonology department due to thoracic pain, haemoptoe and fever. In the
      background of symptoms a 10 cms diameter formation was found in the right thorax
      side joined to the hilus. Even a through row of examination was unable to
      determine the histologic type. After the patient's admittance to the authors'
      thoracic surgery department the tumor occupying the central part of the right
      upper pulmonary lobe was resected by lobectomy via right thoracotomy. The
      histologic result was monophasic synovial sarcoma of which primary pulmonary
      appearance is very rare. The authors consider the rarity of this tumor type worth
      to publish.

PMID- 11300062
TI  - [Surgical treatment of an extremely large sternum protrusion (pectus carinatum)].
AB  - The authors present their special surgical treatment by telling the medical
      history of one of their patients. Cessation of sternum protrusio was achieved by
      a "H" shape resection of the anterior cortical plate of the sternum.

PMID- 11300063
TI  - [Experiences with the modified Fontenelle operation for pericardial effusion].
AB  - The authors summarize their experiences on the surgical treatment of pericardial
      effusions by surveying the clinical data of patients in the last 4 years. They
      call attention on the advantages of subxyphoideal pericardium fenestration, the
      modified Fontenelle operation, which method is routinely used by them.

PMID- 11300064
TI  - [Successfully resected carotid glomus tumor].
AB  - A 76-years old man with carotid body tumor on the left carotid bifurcation was
      operated on, in August 1999. The rare tumor of the paraganglionic tissue was
      detected by ultrasonography and arteriography. Although these tumors have a very
      low incidence of malignancy, extirpation should be carried out. In this case, the
      tumor was removable by blunt and sharp dissection without resecting the fork of
      the carotid artery. The postoperative course was uneventful. They discussed the
      diagnostic and therapeutic steps of solution of this tumors.

PMID- 11300065
TI  - [Late detection of vascular injuries].
AB  - Generally recognizing of traumatical vascular injuries isn't difficult since
      clinical signs and symptoms show them unambiguously. For some time-mainly in case
      of blunt and shot wounds-lacking unanimous signs the vascular injuries can't be
      diagnosed. Later on appearing symptoms as complications raise the chance of
      existence of an earlier vascular injury. In case of three patients the elapsing
      time between the vascular injury and its diagnosis was 4 weeks, 3 years and more
      than 50 years.

PMID- 11300066
TI  - [The use of muscle flaps in the surgical treatment of infected vascular
      prosthesis].
AB  - The solutions for graft infection and its complications in vascular surgery are
      well known. However, publications dealing with this topic do not, or just
      occasionally mention muscular flap plast, which is already quite widely used in
      other fields of surgery. The authors first used pedicled muscular flap plasty in
      1996, to cover grafts that had been exposed as a result of infection. Later, this
      method was also applied in covering subinguinal suturelines and anastomoses
      respectively, to ward off impending haemorrhage. Between 1996 and 1999, 32
      patients presenting with septic complications after vascular surgery were
      treated. Muscular flap plasty was performed in 12 of these cases. In 7 patients
      the exposed graftsere covered, while in 5 patients the subinguinal suture-lines
      and anastomoses were covered respectively with muscle flaps, 5 of the graft
      covering procedures were successful. In two cases of superinfection and septic
      progression respectively the graft had to be removed without amputation of the
      extremity. 3 successful operations were recorded in the cases where the covering
      of the subinguinal suturelines and anastomoses were the aim. 2 patients presented
      with erosive haemorrhage, which led to ligation of the femoral artery and
      consequent amputation, in view of the absence of further possibilities for
      reconstruction.

PMID- 11300068
TI  - [Foreign bodies in the rectum at our department during the last ten years].
AB  - During the past 10 years the authors have treated 17 patients on their department
      because of got stuck or injury-causing rectal foreign bodies. In 12 cases
      swallowed, in 3 cases "per anum"-placed up foreign bodies were observed, in 2
      cases penetrating anorectal injury caused by the foreign body. In 9 cases after
      successful Recamier-dilatation the foreign bodies were removed per anum in 5
      cases they were removed in short time narcosis by rectoscope. At 2 patients they
      had to compose colostoma. All their patients recovered. They stress the
      importance of the removing of the foreign bodies as soon as possible.

PMID- 11300067
TI  - [Intussusception in adults].
AB  - The authors report eight cases of intussusception of small and large intestine in
      adults during five years. 3 of the intussusception caused by simple tumors in
      five cases by malignant. In three cases were chronic presented long term signs
      and symptoms. Ileo-ileal invagination was diagnostised at 3 patients, ileo-caecal
      in one case and ileocolic intussusception also in one case. In 2 cases developed
      caeco-colic, in one case colo-colic invagination. Resection was strongly
      indicated in seven cases and wedge resection was done at the last patient. One
      patient has died of cerebral multiple embilization. They review the etiology and
      pathology, the signs and symptoms as well as the difficulties during diagnosis
      and treatment of the intussusceptions according to their own experience and
      literary datas. The authors draw the attention to the importance of the modern
      iconographic, tools, particularly the ultrasonography in the diagnosis of
      intussusception.

PMID- 11300069
TI  - Public health training and research collaboration in South Eastern Europe.
AB  - The health care systems in South Eastern Europe are characterized by a
      predominantly curative orientation. During the last decade public health became
      insufficient due to war as well as economic and political changes. Today there is
      a lack of competence in public health above all in health management and strategy
      development, but also in the fields of health surveillance and prevention. The
      great need for a sustainable collaboration and support in advanced training and
      continuous education of qualified professionals to reach required conditions was
      recognized. Therefore, the project for the development of training modules and
      research capabilities in public health in South Eastern European countries (SEE)
      was proposed to the Stability Pact (PH-SEE Project). The project is to support
      the reconstruction of postgraduate public health training through development of
      teaching materials in English for the Internet. A regional network of lecturers
      in the health sciences will be established. The up to date texts should be of
      international standard but also be of regional specificity.

PMID- 11300070
TI  - Health care time of crisis, crises in health care--current reality in B&H Health
      Care System.
AB  - In the period from 1945 till 1992 the health protection had constant growth of
      coverage, availability and quality of protection in the promotion of health care
      of the inhabitants, and the health care activity noticed spreading of the network
      of health care institutions, evidently staff improving of all profiles of health
      care workers, and supplying of equipment so said in the accordance with the
      movements in for developed countries. The detaching for health care in 1990
      amounted 6.9 per cent of that time BDP. The period from 1991 till 1955 is
      difficulty to analyze, because of the disturbances which appear in all sphere of
      life and work, and the period from 1996 till 1999 can be analyzed, from the
      already known reasons, only for the area of the Federation. The correct amount of
      the means of payment spent for health care in the postwar period is impossible
      incorrectly to confirm, except detaching from BDP (1999 3.7 per cent) arrived the
      donations in equipment, drugs, sanitary material, training of staff, free of
      charge experts, means for the reconstruction of objects, to this in the future
      cannot be considered. Besides that the rate of detaching for the health care from
      BDP is less than before the war, BDP by it self is far lesser what means that the
      means of payment detached are far lesser. It is necessary the URGENT reform of
      health care financing system, evaluation strategy of the reform of health care
      which up-to-now did not show shifts, the bringing of instruments of planning in
      the health care, instruments of quality control, the legislator must define
      clearly the relations between the private practice, patients and state funds.

PMID- 11300071
TI  - Health condition of the inhabitants of the Federation of Bosnia and Herzegovina
      in 1999.
AB  - In this paper is being presented the health condition of the inhabitants in F
      Bosnia and Herzegovina on the basis of the available negative indicators of
      health as follows: morbidity and mortality. The morbidity is being presented the
      review of the leading diseases of the adult inhabitants old 19 and more years, of
      preschool and school age children. The mortality, as better indicator of health
      condition of the inhabitants, is presented by leading causes of death, according
      the sex and age. These data we compared with those from 1991 and noticed that are
      not recorded great deviations.

PMID- 11300072
TI  - Medical education quality evaluation.
AB  - The scientific-technological dropping back in Bosnia and Herzegovina in the
      postwar period tries to exceed in the different forms of education. The medical
      education represents mostly the transfer of the new informations, and does not
      contain the evaluation of their quality. In the paper is proposed the model of
      quality evaluation of medical education, from the aspect of successfulness and
      achieved degree of new acquired knowledge. The evaluation contains the assessment
      of the structural, processed and original elements. The structural elements
      evaluate the organization and used staff and material resources. The processing
      elements are evaluating the organization and used staff and material resources.
      The processing elements evaluate the applied methodology and contents of the
      subject. The original elements evaluate the organization and used staff and
      material resources. The processing elements evaluate the applied methodology and
      contents of the subject. The original elements evaluate the degree of the
      education goals realization and the level of new aquired knowledge of the
      students in the education. The achieved results of evaluation of quality
      education for the organizers of the seminar will serve as road sign for the
      improvement and achieving of higher degree of the successfulness and quality in
      every phase of education.

PMID- 11300073
TI  - Tobacco smoking, alcohol and drug consumption among youngsters in the Republic of
      Macedonia.
AB  - OBJECTIVE: To evaluate students attitude and behaviour (16 years old) towards
      their lifestyle in consumption of tobacco, alcohol and illegal drugs; drugs'
      availability and the problems related; as well as some social and financial
      aspects; social relations of students etc. MATERIAL AND METHODS: A survey was
      conveyed with students from different ethnic groups--16 years old from every
      school in the country. ESPAD 99 unified questionnaire was used. RESULTS: TOBACCO:
      42% persons responded that they have never taken tobacco in their life. 17% has
      taken a cigarette 1-2 times and 20% have used tobacco over 40 times/occasions
      (Macedonians 22%, Albanians 11% (12 = 24.92 for p < 0.05). During the last month,
      37% youngsters in Macedonia have taken tobacco (in Ireland-41%, Finland 37%,
      Italy 36%, Croatia 32% and Slovenia 19%). ALCOHOL: 31% persons responded that
      they have never tried alcohol in their life (Macedonians 20%, Albanians 77% and
      Turks 76%). Ti is the similar situation for not-taking alcohol during the last
      year (Macedonians 30%, Albanians 83%, Turks 76%) and in the last month (54%
      Macedonians, 88% Albanians and 85% Turks). 33% responded they have been drunk at
      least once in their life 51% Macedonians, 11% Albanians and 14% Turks), and
      during the last month 20%. Most frequent used alcohol drink is wine (4.4% have
      used it over 40 times during the last month). Asked if they think they will take
      alcohol when they will have 25 years, 33% Macedonians, 73% Albanians and 77%
      Turks responded negative. ILLEGAL DRUGS: Around 1/4 stated that their friends are
      taking marijuana. 2.5% stated that most of their friends take marijuana. 8%
      stated that their friend take ecstasy, 3.6% stated that some of their friends
      take heroin. 5% responded they have taken tranquilizers-sedatives in the period
      less than 3 weeks. In average, 2.8% respondents wanted to try illegal drug--Serbs
      (20.6%), Roma (21%) and Macedonians (14.3%), Albanians (6.5) and Turks (6.9%).
      1.28% stated they have smoked heroin 1-2 times. Intravenous heroin used over 40
      times 0.4% respondents. Ecstasy tried 1-2 times 0.64%, alcohol + tablets took
      2.9% respondents. Alcohol and marijuana in the same time tried 1-2 times in life
      time 2.37% or in total 4.13%. Asked if they feel themselves lonely, positively
      responded 28% or 26% Macedonians, 37% Albanians, 35% Turks and 30% Serbs. Asked
      if they are satisfied with the finance situation in their home 32.4% responded
      very satisfied. There is significant difference among different ethnic groups
      (Macedonians 23%, Albanians 71%, Turks 54%, Serbs 27% and Roma 47%). Not
      satisfactory situation is at 8.36% Macedonians, 0.7% Albanians, 2.3% Turks, 5.9%
      Serbs and 5.2% Roma. CONCLUSION: 58% persons responded taken tobacco in their
      life. There are significant differences in alcohol consumption among different
      ethnic groups--Albanians and Turks take alcohol more rarely than Macedonians, due
      to the cultural/religious circumstances. Experimenting with drugs is Ok for males
      more than females. However, youngsters are pretty lonely (1/3 have stated that
      they are lonely most of the time). There is a need for realization of health
      promotional curricula in schools, that will include life skills education and
      strengthening of personality, self esteem development and care for their own
      health to prevent drug addiction.

PMID- 11300075
TI  - Fifty five years of Medical Archives.

PMID- 11300074
TI  - Program of oral health as a part of the public health program in Republic Serbia.
AB  - Special attention is given by the health legislation for protection of vulnerable
      groups and those who are exposed to high risk. The system of health care service
      is restructured and expanded in the way that accessibility, efficiency and
      effectiveness are improved. Public health insurance programme has priority and
      funds are ensured from the budget and the national health service for its
      execution. The programme of oral dental health is the component of the Public
      Health programm. This Programme has been continually implemented for more than 5
      years. This Programme defines particular aims which are realized through
      following: systematical health educations, fluor protection, oral hygiene, proper
      nutrition, systematical sanitation. It is realized in the whole Republic but with
      different success. Regional and communal health centers are included in executing
      this Programme, particularly dentistry as the bearer of these activities, then
      pediatrics, gynaecology, community-health service, etc. One part of the Programme
      is directed to include other society segments to give it support (education,
      water supply, food producers, mass media, etc.). The results show that the
      Programme is effective and that the oral dental health of the inhabitants in
      Serbia has been considerably improved for the last 5 years.

PMID- 11300076
TI  - Medicine ethics as a public problem.
AB  - Ethics, especially medical ethics, is of a great importance in medical
      informatics field ethical principles have great importance in confidentiality,
      security, and access to patient records. This is not as simple problem as it
      looks in the first sight, and--in that context--it is significant that many
      jurisdictions have drafted laws in this regard. As medical informatics has been
      developed, this ethical problem is becoming very important for medical
      informatics. Many efforts to make fundamental principles "according to which data
      protection and access to official information could be reconciled" are made. The
      principles described in this paper are independent of any process, as they are
      based on ethical principles. It avoids any kind of conflict or misunderstandings.
      They can be a base for making of an ethical code for informatics in health care
      delivery. These principles are independent of any particular "laws", and they can
      serve as to establish uniformity of standards in medical informatics.

PMID- 11300077
TI  - Development of community psychiatry in Bosnia-Herzegovina with focus on support
      from Sweden.
AB  - The mental health reform basically means a movement of patients from the former
      institutions into the society. The driving forces have been human rights and
      economical reasons. In Bosnia-Hercegovina the war became a starting point for the
      mental health reform. With support from major international organisations such as
      WHO, The World Bank and Unicef and minor NGOs such as SweBiH, and HNI Bosnia
      Hercegovina has done a remarkable progress in a few years time. SweBiH has co
      operated with HNI and focused on training of personnel from different professions
      during four years and examples are given. The future support might be a Training
      Centre for Community Psychiatry in Sarajevo. SweBiH plans to continue with
      support of sustainable research activities.

PMID- 11300078
TI  - Health inequality in Slovenia.
AB  - The aim of this study was to correlate some socio-economic factors (gender,
      income, education, social position) with some health indicators (life expectancy,
      death rate by selected causes of death, self-evaluation of one's own health,
      absence from work due to illness or injuries) with a purpose to define the
      ineqaulity in health across Slovenian municipalities. In our study two sources of
      data for the population of Slovenia in 1996 were used: from the Statistical
      Office of the Republic of Slovenia (aggregated data across Slovenian
      municipalities) and Public Opinion Research (individual data). Statistical
      analysis was performed by correlation and factor analysis. The correlation
      coefficient between education and life expectancy is 0.712. The correlation
      between income base and life expectancy is also significant (0.707). In the
      eastern part of the country (mostly rural population) women in average live 2
      years and men 3 years less than their counterparts in the western part of the
      country. Five causes of death across Slovenian municipalities are significantly
      related to the population's education and incomes, of which only death due to
      neoplasm is positively correlated to income while all other causes are negatively
      correlated not only with income but also with education. Health (self-evaluation)
      is closely related to an individual's education and social position. The factor
      analysis of pressures at work showed groups of two factors as being the most
      significant: pressures related to leadership positions (positive correlation with
      health), and physical labour or work in inferior positions (negative correlation
      with health). We can conclude that the results of our study showed the crucial
      effect of investigated socio-economic factors on people's health across Slovenian
      municipalities. During the present socio-economic transition period we are trying
      to establish new sources of data and looking for possibilities to connect and
      refine them for further investigation.

PMID- 11300079
TI  - Public health in Bosnia and Herzegovina.
AB  - It has been presented flow of socio-medical development and implementation on
      former Yougoslavia and Bosnia and Herzegovina territory in last thirty years. The
      names of those who are deserved for socio-medical development and its
      insufficiency on the organization on health system and some specific parts of it.
      Doubtlessly, the social medicine, as science and profession, and specially that
      one in Bosnia and Herzegovina, had high level among other disciplines, but also
      as profession per se, specially at the International level. There is huge
      evidence of numerous projects, congress papers, recognized by indigenous and
      international audience.

PMID- 11300080
TI  - Population and health.
AB  - Population and health ecology as subsystems of the health system are of special
      interest for public health. The population as a financer and beneficiary of
      health care determines various needs and possibilities of their realization. In
      order to establish solid socio-medical diagnosis of population, it is the key
      parameter, which is being realized through population statistics considering the
      number and distribution of population according to biological, socio-economic and
      cultural characteristics, as well as through vital and migration statistics.
      Health ecology as a subsystem represents the interest of public health from the
      aspect of monitoring of ecology expositions and the state of other contents of
      ecology and their impact on health. The establishment of sustainable development
      of human environment represents a philosophy, which is based on inter-generation
      equality meaning that present generation should give the future generation an
      environment in which is possible to live healthy life and realise any other
      progress. Population and health ecology are subsystems within which is necessary
      to seek needs that have to be met with the aim of improvement of population in
      terms of health.

PMID- 11300081
TI  - [Hydrodynamic properties of exopolysaccharide-acrylamide copolymer].
AB  - The method for producing copolymer EPAA of exopolysaccharide (EPS)-
      polyacrylamide (PAA) has been presented which was based on microbial
      exopolysaccharides (enposane, xampane), their mixture and model EPS (xanthane
      sigma, rodopol P-23). The copolymer was produced by acrylamide polymerization in
      1-2% water solutions of polysaccharides, the concentration of acrylamide in the
      reaction mixture being 4.7-2% and that of polysaccharides 0.1-1% of the weight.
      Hydrodynamic parameters of the studied polymers have been determined, their
      heterogenity as to molecular-weight characteristics has been demonstrated.
      Molecular-weight distribution of copolymers showed that the content of low
      molecular fractions decreased, thus the Mw values were (0.08-0.2) x 10(6) Da in
      contrast to that of exopolysaccharides possessing Mw (1.2-0.4) x 10(6) Da and of
      polyacrylamide possessing Mw within (2-30) x 10(6) Da. The value of efficient
      viscosity of copolymers ranged from 120 to 131 mPa.s that was lower than that of
      polyacrylamide (500 mPa.s), and higher than that of exopolysaccharides (42
      mPa.s), and it depended on the sample, raw material, production conditions. A
      possibility has been shown to produce a new copolymer based on microbial
      polysaccharides enposane and xampane in the process of acrylamide polymerization.
      It has been found out that the studied copolymers EPAA differ from initial ones
      as to their hydrodynamical properties, which determines their preference: better
      solubility, good glueing properties, prolonged term of preservation, resistance
      to bacterial pollution.

PMID- 11300082
TI  - [Effect of microelements on accumulation of biomass and exopolysaccharides in
      Bacillus subtilis strains].
AB  - Different trace elements in the composition of nine synthesized complex compounds
      of N-oxides of pyridine derivatives have been studied. It has been shown that the
      effect of trace elements included in the composition of nutrient media on
      accumulation of cells and exopolysaccharides (EPS) by the strains of B. subtilis
      is sufficiently expressed; it is also diverse and depends on the element nature,
      concentration as well as on peculiarities of the bacillus cultures. The studied
      trace elements are separated into the conditional groups: the elements
      intensifying the above processes (manganese and lithium); elements repressing the
      processes (copper and cadmium); those retarding the accumulation of biomass but
      activating the secretion of EPS (nickel, boron, cobalt, zinc, iron).
      Concentrations of trace elements optimal for the studied productivity indices of
      strains have been established. Peculiarities of the trace element effect in
      paired and ternary combinations on the growth and biosynthesis of EPS during
      cultivation of strains in liquid media have been revealed.

PMID- 11300083
TI  - [Activity of tricarboxylic acid cycle enzymes in cyanobacteria Spirulina
      platensis].
AB  - The activity level and some physico-chemical properties of enzymes of the
      tricarboxylic acid cycle (TCA cycle) and the associated enzymes isocitrate lyase
      and glutamate dehydrogenase of cyanobacterium Spirulina platensis grown under
      illumination of 5000 lk in batch conditions, have been studied. High activities
      of most of the studied enzymes except for alpha-ketoglutarate dehydrogenase
      (alpha-KGDH) and succinate dehydrogenase have been estimated. In some cases the
      activities were by an order higher than that of similar enzymes in other
      cyanobacteria. This reflects the microorganism ability to synthesize intensively
      organic substances and first of all protein. Absence of alpha-KGDH activity
      proves that TCA cycle of spirulina has a limited value for energy generation and
      mainly performs the biosynthetic function.

PMID- 11300084
TI  - [Alternative mechanisms of detoxication of formaldehyde, formate, and hydrogen
      peroxide in methylotrophic yeasts].
AB  - A new concept based on own experimental results and published data and concerning
      the involvement under extreme conditions of additional (nontraditional)
      mechanisms of formaldehyde, formate and hydrogen peroxide detoxification in
      methylotrophic yeast has been proposed. It has been shown that neutralization of
      toxic effect of formaldehyde and formate, except the known ways, includes a
      system of energy-dependent extrusion of formic acid into extracellular space.
      Detoxification of hydrogen peroxide, besides of catalase way, can be realized by
      means of cytochrome c peroxidase reaction. The proposed concept has been built on
      the basis of physiological and biochemical analysis of specially constructed
      mutants strains of methylotrophic yeast with certain metabolic damages. The
      selected mutants, used as the instrument in fundamental studies of detoxification
      processes, also have been successfully used for practical purposes in
      construction of cell biosensors and creation of enzymatic kits.

PMID- 11300085
TI  - [Unique properties of highly radioresistant bacteria].
AB  - In connection with the Chernobyl Nuclear Power Plant (ChNPP) accident and the
      negative ecological after-effects for biota in this zone the interest has arisen
      to radioresistant bacteria, as to the most dynamic model of the given ecosystem,
      and to mechanisms which provide resistance of bacteria to ionizing radiation. The
      analysis of published data has shown that the radioresistant bacteria are not
      interrelated taxonomically and phylogenetically. The extreme radioresistant
      bacteria are represented by the Deinococcus species, which form a group
      phylogenetically close to the line Thermus-Meiothermus. Other radioresistant
      bacteria are the representatives of the genera Rubrobacter, Methylobacterium,
      Kocuria, Bacillus and some archebacteria. Data on natural habitats, of
      radioresistant bacteria are not numerous. In a number of cases it is difficult to
      distinguish their natural habitats, as they were isolated from the samples which
      were previously exposed to X-ray or gamma-irradiation, or from the ecosystems
      with the naturally raised radioactivity. To understand the strategy of survival
      of radioresistant bacteria, we briefly reviewed the mechanism of action of
      various species of radiation on cells and macromolecules; physiological signs of
      the cell damage caused by radiation; mechanisms eliminating (repairing) these
      damages. More details on mechanisms of the DNA repair in D. radiodurans are
      described. The extreme resistance of D. radiodurans to the DNA damaging factors
      is defined by 1) repair mechanisms which fundamentally differ from those in other
      procaryotes; 2) ability to increase the efficiency of a standard set of the DNA
      repairing proteins. Literary and own data on the effect of radiation on survival
      of various groups of bacteria in natural ecosystems are summarized. The
      ecological consequences of the ChNPP accident for soil bacteria in this region
      were estimated. The reduction of the number of soil bacteria and recession of
      microbial diversity under the effect of anthropogenic radiation was shown.

PMID- 11300086
TI  - [Immunosuppressive properties of virulent Shigella strains].
AB  - The review presents data which show the existence of significant difference
      between the virulent and avirulent Shigella species. This difference is displayed
      in the virulent Shigella's ability to inhibit immune memory and secondary immune
      response. The existance of immunosuppressive activity in virulent Shigella has
      been demonstrated in the case of experimental Shigella infection in animals as
      well as natural infection in humans. The immunosuppressive property of Shigella
      sonnei is determined by the invasiveness genes of the virulence plasmid.
      Lipopolysaccharide (LPS) from virulent Shigella sonnei differs from the avirulent
      Shigella sonnei LPS. It possesses the property to induce in avirulent bacteria
      the ability to inhibit secondary immune response. This inductive
      immunosuppressive property of LPS is also encoded by invasiveness genes. Thus,
      literature data suggest that the ability to inhibit immune memory, secondary
      immune response and the existence of inductive immunosuppressive property in LPS
      are Shigella's signs of virulence as well as its ability to invade epithelial
      cells.

PMID- 11300087
TI  - [Application and development of information technologies in the multidisciplinary
      hospital].

PMID- 11300088
TI  - [From education for the life time--to education through the life time].

PMID- 11300089
TI  - [Contribution of military medicine to creation of Strategic Missile Troops].

PMID- 11300090
TI  - [A case of sparganosis].

PMID- 11300091
TI  - Pleuropulmonary blastoma: report of a case presenting with spontaneous
      pneumothorax.

PMID- 11300092
TI  - Long-term efficacy of epicardial radiofrequency ablation of chronic atrial
      fibrillation during mitral valve surgery.

PMID- 11300093
TI  - Arterial flow determined with half Fourier echo-planar imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has become a powerful imaging
      modality to quantify blood flow. To gain insight of the hemodynamics of the human
      cardiovascular system, acquisition time of MR images must be reduced. It is
      necessary to produce faster imaging methods to avoid motion artifacts, such as
      blurring and ghosting, which alter the image quality. To solve this problem a
      flow-encoded Echo-Planar Imaging (EPI) sequence combined with a Half Fourier
      method is proposed to determine blood flow in the cardiovascular system. METHODS:
      This imaging modality was used to quantify blood flow in large vessels such as
      the human aorta. We acquired transaxial 128x128 images, with a slice of 1-cm
      thickness and 2.5 mm in-plane resolution. All these images were used to measure
      blood flow in the ascending aorta and descending aorta of nine healthy male
      volunteers and one female volunteer, ages 22-35 years. RESULTS: Velocity profiles
      and blood flow maps were obtained from healthy volunteers and compared with other
      imaging techniques. CONCLUSIONS: It has been demonstrated that Half Fourier EPI
      flow sequence can become a suitable flow measurement technique for real-time
      magnetic resonance angiography. It provides us with morphological and functional
      information of the cardiovascular system.

PMID- 11300094
TI  - ECNP Consensus Meeting March 2000 Nice: guidelines for investigating efficacy in
      bipolar disorder. European College of Neuropsychopharmacology.

PMID- 11300095
TI  - Oral dietary supplements before and after surgery.

PMID- 11300097
TI  - ECG of the month: ectopic and junctional rhythms.

PMID- 11300096
TI  - Homocysteine, folate, and dysplasia: who is the enemy?

PMID- 11300098
TI  - The ten most commonly asked questions about hormone replacement therapy.

PMID- 11300099
TI  - Periumbilical contact vitiligo appearing after allergic contact dermatitis to
      nickel.

PMID- 11300100
TI  - Current and future technologies for breast cancer imaging.

PMID- 11300101
TI  - Application of magnetic resonance imaging to early detection of breast cancer.
AB  - Since its introduction approximately 10 years ago, there has been extensive
      progress in the application of magnetic resonance imaging (MRI) to the detection
      and diagnosis of breast cancer. Contrast-enhanced MRI has been shown to have
      value in the diagnostic work-up of women who present with mammogram or clinical
      abnormalities. In addition, it has been demonstrated that MRI can detect
      mammogram occult multifocal cancer in patients who present with unifocal disease.
      Advances in risk stratification and limitations in mammography have stimulated
      interest in the use of MRI to screen high-risk women for cancer. Several studies
      of MRI high-risk screening are ongoing. Preliminary results are encouraging.

PMID- 11300102
TI  - Application of magnetic resonance imaging to angiogenesis in breast cancer.
AB  - Magnetic resonance imaging (MRI) techniques enable vascular function to be mapped
      with high spatial resolution. Current methods for imaging in breast cancer are
      described, and a review of recent studies that compared dynamic contrast-enhanced
      MRI with histopathological indicators of tumour vascular status is provided.
      These studies show correlation between in vivo dynamic contrast measurements and
      in vitro histopathology. Dynamic contrast-enhanced MRI is also being applied to
      assessment of the response of breast tumours to treatment.

PMID- 11300103
TI  - A transient dysfunction of the neuromuscular junction due to carbendazim
      intoxication.

PMID- 11300104
TI  - Refsum's disease in an Arabian family.

PMID- 11300105
TI  - A case of malignant lymphoma exhibiting multiple cranial nerve enhancement:
      leptomeningeal metastasis? Or another lymphoma associated event?

PMID- 11300106
TI  - The Glu298Asp polymorphism in the NOS3 gene is not associated with sporadic
      Alzheimer's disease.

PMID- 11300107
TI  - How well does the Oxfordshire Community Stroke Project classification predict the
      site and size of infarct of brain imaging?

PMID- 11300108
TI  - [Multiple carcinoid tumors of the small intestine and associated tumors].

PMID- 11300109
TI  - [Hypersensitivity to mesalazine after severe allergic reaction to sulfasalazine].

PMID- 11300110
TI  - [Severe retroperitoneal hemorrhage due to erosion of the left renal artery by a
      pancreatic pseudocyst].

PMID- 11300111
TI  - [Transnasal percutaneous endoscopic gastrostomy ].

PMID- 11300112
TI  - [Peritoneal granulocytic sarcoma: a differential diagnosis of peritoneal cancer].

PMID- 11300113
TI  - [Progression of a hepatic hemangioma under progestins].

PMID- 11300114
TI  - [Liver transplantation with an intrafamilial living donor in the French context].

PMID- 11300115
TI  - [Cancer of the rectum: progress contributed by total excision of the mesorectum.
      The example of a county in Stockholm: history of success in the apprenticeship
      method].

PMID- 11300116
TI  - [Artificial nutrition: indications, methods, results].

PMID- 11300117
TI  - [Diarrhea from enteral nutrition].

PMID- 11300118
TI  - [Artificial nutrition. Bibliographic review].

PMID- 11300119
TI  - [Questions for Professor Eric Lerebours].

PMID- 11300120
TI  - Francis Hancock Balkwill.

PMID- 11300121
TI  - Methods for obtaining and analyzing unattended polysomnography data for a
      multicenter study. Sleep Heart Health Research Group.
AB  - This paper reviews the data collection, processing, and analysis approaches
      developed to obtain comprehensive unattended polysomnographic data for the Sleep
      Heart Health Study, a multicenter study of the cardiovascular consequences of
      sleep-disordered breathing. Protocols were developed and implemented to
      standardize in-home data collection procedures and to perform centralized sleep
      scoring. Of 7027 studies performed on 6697 participants, 5534 studies were
      determined to be technically acceptable (failure rate 5.3%). Quality grades
      varied over time, reflecting the influences of variable technician experience,
      and equipment aging and modifications. Eighty-seven percent of studies were
      judged to be of "good" quality or better, and 75% were judged to be of sufficient
      quality to provide reliable sleep staging and arousal data. Poor submental EMG
      (electromyogram) accounted for the largest proportion of poor signal grades (9%
      of studies had <2 hours artifact free EMG signal). These data suggest that with
      rigorous training and clear protocols for data collection and processing, good
      quality multichannel polysomnography data can be obtained for a majority of
      unattended studies performed in a research setting. Data most susceptible to poor
      signal quality are sleep staging and arousal data that require clear EEG
      (electroencephalograph) and EMG signals.

PMID- 11300122
TI  - [Underlying cause of death from external causes: validation of official data in
      Recife, Pernambuco, Brazil].
AB  - OBJECTIVE: To validate the underlying cause of death recorded on the death
      certificates for individuals under 20 years of age who died from external causes
      in 1995 in Recife, Pernambuco, Brazil. METHODS: We divided the study into two
      stages, coding and validation. In both stages we compared the official data
      concerning causes of death to the data we obtained during our study. We grouped
      the death certificates into 5 broad categories according to the cause of death;
      we later subdivided them into 14 categories. We also individually compared the
      death certificates applying the four-digit system of the International
      Classification of Diseases, Ninth Revision (ICD-9). We assessed the agreement
      between the official data and our data in terms of sensitivity and the kappa
      coefficient. We took as the standard the categorization of the cause of death
      that we had made during our investigation. RESULTS: In the coding stage,
      considering all the external causes of death, the overall agreement between the
      official data and our study data was 94% for the 5 categories, 92% for the 14
      categories, and 81% for the four-digit ICD-9 system. In the validation stage the
      overall agreement was 94% for the 5 categories, 91% for the 14 categories, and
      73% for the four-digit ICD-9 system. CONCLUSIONS: Our results suggest that for
      the death certificates to be reliable, the Institute of Legal Medicine must fill
      them out following recommended standards. In addition, hospitals and police
      departments must use greater care in completing the transfer slips that accompany
      the bodies that are sent to the Institute. More accurate data need to be
      generated and disseminated for a society to better understand its patterns of
      violence.

PMID- 11300123
TI  - CCR5 and beta-chemokines in HIV-1 infected children.
AB  - The duration from initial infection with HIV-1 to CD4 lymphocyte depletion and
      progression to AIDS varies among infected individuals. Despite treatment with
      highly active antiretroviral therapy (HAART), patients still show different
      stages of disease progression. We examined the role of beta-chemokines and its
      receptor, CCR5 in HIV-1 infected children in order to define determinants of HIV
      progression among treated individuals. Population was divided in two groups:
      Group 1--Long Term Non Progressors (LTNP) includes 10 patients with B1-B2 CDC
      disease classification and with a less aggressive therapy (only 2 in HAART);
      Group 2--Rapid Progressors (RP) includes 9 patients with C3 disease
      classification. All the patients had a CCR5 wild type (wt) genotype indicating
      that they do not have the 32 base-pair deletion associated with slower
      progression. There was an increased production of MIP 1-beta in 8/10 LTNP but
      only in 4/9 Progressors (Paired t-test/Wilcoxon Sign test, p-value < 0.05). The
      change in the levels of MIP-1 beta after PHA stimulation was statistically
      significant in both groups. The levels of RANTES increased in LTNP and RP and the
      change of the levels after mitogen stimulation was statistically significant for
      both groups included. The production of RANTES and MIP-1 beta in response to
      stimulation between both groups was not statistically significant. The production
      of MIP-1 alpha was variable in both groups and the difference in the levels after
      mitogen stimulation between the groups was not statistically significant. These
      results suggest that beta-chemokines do not play an important role in HIV-1
      progression in children undergoing HAART.

PMID- 11300124
TI  - [Constitutional syndrome with loss of functional capacity of the lower left limb
      in a 76 year-old man].

PMID- 11300126
TI  - Attitude.

PMID- 11300125
TI  - [New strategies for treatment of chronic hepatitis C].

PMID- 11300127
TI  - Distal biceps tendon ruptures: a historical perspective and current concepts.
AB  - Distal biceps tendon rupture is a relatively rare injury most commonly seen in
      the dominant extremity of men between 40 and 60 years of age. It occurs when an
      eccentric extension force is applied to a contracting biceps muscle. The hallmark
      finding is a palpable defect in the distal biceps, which is accentuated by elbow
      flexion. Radiographic evaluation is usually not necessary. Acute surgical repair
      is advocated for optimal return of function by either a one-incision or a
      modified two-incision muscle-splitting technique. The arm is protected for 6 to 8
      eight weeks after surgery. Unrestricted range of motion and gentle strengthening
      may begin after the 6 - 8 week protection period. Return to unrestricted activity
      is usually allowed by 5 months after surgery.

PMID- 11300128
TI  - Abduction-and-horizontal-adduction technique for reduction of acute anterior
      shoulder dislocations: a simple technique evaluated with radiographs.
AB  - Forty-five acute anterior shoulder dislocations were reduced by an abduction-and
      horizontal-adduction technique performed in the supine position. Forty-one (91%)
      of the 45 dislocations were reduced successfully on the first attempt using this
      technique, without anesthesia or assistance. There were no complications
      attributed to the technique. To clarify the reduction maneuver using this
      technique, the procedure was evaluated with radiographs. With horizontal
      adduction and gentle traction applied at 90 degrees of abduction, the scapula
      maximally shifted anteriorly with superior rotation, allowing the dislocated
      humeral head to be reduced. The long head of the biceps tendon seems to have an
      important role in this reduction technique, along with the musculotendinous units
      of the rotator cuff.

PMID- 11300129
TI  - Foraminal stenosis of the lumbar spine: a review of 65 surgical cases.
AB  - This study provides clinical and radiographic information and characteristics
      that may best define the presence of significant lumbar foraminal stenosis and
      reports on the outcome of surgical intervention. Although anatomy of the lumbar
      intervertebral foramen (including static and dynamic pathologic compression of
      the exiting nerve root) has been described, few studies have focused on the
      clinical and radiographic features of foraminal stenosis requiring surgical
      intervention. We retrospectively studied 65 patients with lumbar foraminal
      stenosis for presenting clinical and radiographic features and intraoperative
      findings. Symptoms included leg and back pain (100%), paresthesias (45%), and
      subjective weakness (31%). Examination revealed lumbar tenderness (71%), limited
      lumbar extension (57%), focal motor weakness (48%), and positive tension signs
      (42%). The L5 nerve root was most often involved (75%). Almost 50% of patients
      had already undergone spinal decompression surgery. Surgical procedures included
      laminectomy and foraminotomy (52 patients) and laminotomy and foraminotomy (23
      patients). A concomitant arthrodesis was performed in 63 patients. There were 29
      excellent, 25 good, 6 fair, and 5 poor results based on a modified outcome scale
      at 32.5-month follow-up. Findings suggest that foraminal stenosis is a frequent
      cause of persistent symptoms after surgery, is most common at the lumbosacral
      junction, is best identified on parasagittal magnetic resonance images or on
      images reconstructed with computed tomography, and may be static or dynamic in
      etiology.

PMID- 11300130
TI  - Exterior carpi radialis longus tendinoplasty for thumb basal joint arthritis.
AB  - Thumb carpometacarpal arthritis has been successfully treated with a combination
      of trapezium excision, ligament reconstruction, and tendon interposition (most
      commonly with the flexor carpi radialis [FCR] tendon). We describe a technique
      using the extensor carpi radialis longus (ECRL) tendon and show, through
      dissection of 36 cadaver hands, the close relationship between this tendon and
      the intermetacarpal ligament. Of 16 patients (19 hands) managed with this
      technique, 95% were satisfied at a mean follow-up of 42 months. We conclude that
      ligament reconstruction and ECRL tendon interposition constitute a viable
      treatment option for carpometacarpal joint arthritis, especially when the FCR
      tendon is unavailable or its use is undesirable.

PMID- 11300131
TI  - Synovial chondromatosis of the elbow.
AB  - Synovial chondromatosis is an uncommon disorder with rare occurrence in the
      elbow. Case reports in the literature for elbow synovial chondromatosis have
      described presenting symptoms secondary to peripheral nerve compressions or
      localized bursitis. We discuss a case of synovial chondromatosis of the elbow
      that presented as an isolated soft-tissue mass over the radial head-more
      suggestive of a soft-tissue tumor than of synovial chondromatosis.

PMID- 11300132
TI  - Isolated fracture of the trapezoid.
AB  - We describe a case of an isolated trapezoid fracture that was managed
      nonoperatively with a favorable clinical outcome. To our knowledge and based on a
      literature review, this is the first report of a true isolated trapezoid fracture
      without accompanying dislocation and without associated metacarpal, carpal, or
      distal radial fractures. We present our findings in this case and review the
      clinical presentation, diagnostic workup, and treatment of trapezoid fractures in
      general.

PMID- 11300133
TI  - Trigger wrist caused by a tumor of the tendon sheath in a teenager.
AB  - Triggering of the flexor tendons at the wrist is a rare phenomenon. It usually
      occurs in adult patients, and the manifestations and etiology can vary. We
      present a teenager with triggering and symptoms of carpal tunnel syndrome caused
      by a fibroma of the tendon sheath originating from the flexor tendons in the
      carpal canal.

PMID- 11300134
TI  - Distal third fibular aneurysmal bone cyst: en bloc resection and proximal third
      fibular reconstruction.
AB  - Treatment of aneurysmal bone cysts (ABCs) located in the distal third fibula
      adjacent to the growth plate, can be problematic. The first choice of treatment
      for these lesions has been cyst curettage and bone graft. Complications include
      the high recurrence rate, possible growth-plate injury, and possible ankle
      instability associated with that treatment led to the development of other
      surgical options. We used en bloc resection and proximal third fibular bone
      reconstruction to treat an 8-year-old female patient with a distal third fibular
      ABC close to the growth plate. There was no recurrence, growth-plate injury, or
      ankle instability at 30-month follow-up.

PMID- 11300135
TI  - Assessment of distal radial articular surface by angled radiography.
AB  - A common complication of surgical management of fractures of the lower radius
      involves hardware penetration of the articular surface. If neglected, this
      complication will lead to wrist joint degeneration. The authors of this study
      describe a plain roentgenographic angled view of the wrist that provides
      visualization of the distal radial articular surface to detect any hardware
      penetration. This view can also be used during surgery by means of an image
      intensifier.

PMID- 11300136
TI  - Importance of correlating static and dynamic imaging studies in diagnosing
      degenerative lumbar spondylolisthesis.
AB  - Degenerative spondylolisthesis in the lumbar spine is due to long-standing
      segmental instability. A standing plain radiograph is commonly the only imaging
      study needed to establish the diagnosis. Translatory motion in spondylolisthesis
      is traditionally assessed with lateral flexion and extension radiographs. These
      dynamic studies often demonstrate a decrease in the slip percentage between the
      vertebral segments with extension and an increase with forward flexion. Some low
      grade spondylolisthetic deformities reduce anatomically on the operating table
      after the administration of an anesthetic. We encountered one case in which there
      was complete reduction of an L4-5 grade I degenerative spondylolisthesis with
      positioning of a non-anesthetized patient in the supine position during a
      lumbosacral magnetic resonance imaging (MRI) scan. The patient's condition was
      originally misdiagnosed, as the spondylolisthesis was not identified on recumbent
      plain radiographs or on lumbosacral MRI. This case stresses the importance of
      correlating static and dynamic imaging studies in developing a treatment plan for
      patients with degenerative spondylolisthesis.

PMID- 11300137
TI  - Elbow aspiration and arthrogram: an alternative method.
AB  - We describe a posterior elbow-aspiration approach that is safe, easy, and
      effective in all settings, including trauma.

PMID- 11300138
TI  - Rotator cuff injury.

PMID- 11300139
TI  - Estrogen therapy in a male patient with chronic hepatitis C and irradiation
      induced testicular dysfunction.
AB  - We report an 18-year-old male patient who developed chronic hepatitis C after
      blood transfusion and had testicular dysfunction after irradiation for a
      testicular relapse of childhood acute lymphocytic leukemia after cessation of
      maintenance therapy, and the initiation of testosterone replacement therapy at
      puberty. Concomitant administration of estradiol resulted in a reduction in serum
      alanine aminotransferase and ferritin levels and hepatic iron concentration and
      staining after 2 years of estrogen therapy, although interferon therapy was
      withdrawn because of adverse effects. This observation suggests that endogenous
      estradiol may play a beneficial role in male patients with chronic hepatitis C.

PMID- 11300140
TI  - Giant negative T waves during interferon therapy in a patient with chronic
      hepatitis C.
AB  - Interferon-alpha (IFN-alpha) has been widely used for treatment of chronic
      hepatitis C in Japan. In general, cardiovascular adverse reactions are rare in
      association with IFN-alpha therapy. Here, a 64-year-old man with chronic active
      hepatitis C complained of fatigue, palpitation and depression, and developed
      atrial fibrillation with prominent negative T waves during IFN-alpha therapy.
      Echocardiogram showed septal and apical hypertrophy. Three days after
      discontinuation of IFN-alpha, subjective symptoms and atrial fibrillation
      subsided. It is unclear whether or not IFN-alpha induced the giant negative T
      waves with apical hypertrophy. We might observe the developing course of
      hepatitis C virus (HCV)-related myocardial hypertrophy by chance. Cardiovascular
      toxicity should be carefully monitored during IFN-alpha therapy even in patients
      with minor cardiac disease, such as premature ventricular contracture (PVC) and
      mild hypertension.

PMID- 11300141
TI  - Familial idiopathic hypoparathyroidism, sensorineural deafness and renal
      dysplasia.
AB  - We describe a 27-year-old woman with familial idiopathic hypoparathyroidism,
      bilateral sensorineural deafness and right renal aplasia. There was a family
      history of deafness in her father and two other family members with sensorineural
      deafness, one of whom had hypoparathyroidism. To our knowledge, there have been
      four previous reports of idiopathic hypoparathyroidism associated with
      sensorineural deafness and renal dysplasia. The clinical features were not
      identical to any of the four previous reports. Although no chromosome
      abnormalities were present in the patient using standard trypsin G-banding
      analysis, we speculate that some common genetic mutation caused
      hypoparathyroidism, sensorineural deafness and renal dysplasia.

PMID- 11300142
TI  - Successful steroid therapy for cefdinir-induced acute tubulointerstitial
      nephritis with progressive renal failure.
AB  - A 58-year-old woman was admitted to our hospital because of renal dysfunction
      that continued to progress even after withdrawal of cefdinir, the presumed cause
      of acute renal failure. Renal histologic findings included interstitial fibrosis
      accompanied by moderate lymphocytic infiltration, and tubular atrophy with
      reduced numbers of epithelial cells. Mesangial cells and glomerular basement
      membranes were nearly normal. Scintigraphy with 67gallium disclosed diffuse
      abnormal accumulation in both kidneys. A lymphocyte stimulation test with
      cefdinir was positive. The patient was diagnosed with acute tubulointerstitial
      nephritis caused by cefdinir. Serum creatinine concentrations continued to rise
      after withdrawal of the drug, but steroid therapy was effective in normalizing
      renal function.

PMID- 11300143
TI  - Fulminant pneumonia due to Aeromonas hydrophila in a man with chronic renal
      failure and liver cirrhosis.
AB  - A 40-year-old man on hemodialysis was admitted due to dyspnea and chest pain and
      was diagnosed with pneumonia and pericarditis. Ampicillin was administered, but
      thereafter severe septic shock developed. The fulminant type of pneumonia
      progressed rapidly, and he died only 48 hours after the onset of symptoms. The
      autopsy and sputa culture revealed pneumonia due to Aeromonas hydrophila. The
      source of this infection remained unkown. Interestingly, there were two types of
      A. hydrophila found during such a short period. The physician should suspect this
      disease by questioning the patient's history. Early treatment with adequate
      antibiotics is the only means of saving such a patient's life.

PMID- 11300144
TI  - Analgesic-induced asthma caused by 2.0% ketoprofen adhesive agents, but not by
      0.3% agents.
AB  - A 74-year-old woman was admitted with an asthma attack. She had a 40-year history
      of sinusitis, nasal polyp and analgesic-induced asthma; however, asthma had never
      occurred when she used a 0.3% ketoprofen adhesive patch (Mohrus) for stiff
      shoulder or lumbago. In the hospital, a life-threatening asthma attack suddenly
      occurred two and a half hours after application of a 2.0% ketoprofen adhesive
      tape (Mohrus tape) to her shoulder. She was treated with bronchodilator and
      glucocorticoid and extubated after 20 hours. A drug lymphocyte stimulating test
      (DLST) was strongly positive for ketoprofen. We suspected that drug-induced
      hypersensitivity coexisted in the present case, but it was not clear whether or
      not the hypersensitivity was related to the pathogenesis of analgesic-induced
      asthma.

PMID- 11300145
TI  - Sarcoid reaction in primary tumor of bronchogenic large cell carcinoma
      accompanied with massive necrosis.
AB  - A 49-year-old woman consulted our hospital for evaluation of a tumor with
      cavitation in the S6 segment of the right lung. She was given a diagnosis of
      pulmonary tuberculoma because percutaneous needle aspiration cytology revealed
      epithelioid cells with a background of necrosis. However, a diagnosis of large
      cell carcinoma with central necrosis (p-T2NOM0) was established by thoracoscopic
      lung biopsy six months later. Pathological findings of surgical resection
      specimens showed that epithelioid cell granulomas adjacent to the neoplasm had a
      sarcoid reaction and the necrosis was related to the rapidly growing tumor
      because there was no clinical evidence of systemic sarcoidosis and pulmonary
      mycobacterial or fungal infection. This is the first report in which sarcoid
      reactions were recognized in a primary large cell carcinoma.

PMID- 11300146
TI  - Rhabdomyolysis triggered by an asthmatic attack in a patient with McArdle
      disease.
AB  - We describe a patient with McArdle disease who developed rhabdomyolysis triggered
      by a bronchial asthmatic attack. A 64-year-old man had chronic pulmonary
      emphysema with asthma, and an asthmatic attack led to severe rhabdomyolysis that
      required continuous hemodiafiltration. After 2 years, a physical examination
      revealed atrophy of the extremities compared with previous examinations,
      especially of the intercostal muscles. During that time, he suffered two severe
      bronchial asthmatic attacks. His serum level of creatinine kinase remained
      between 4,000 and 7,000 IU/l when he did not suffer from asthmatic attacks and
      rhabdomyolysis had abated. Therefore, we suspected that his recent muscle atrophy
      was caused by asthmatic attacks, and discussed the possibility of his respiratory
      muscle weakness due to McArdle disease in relation to his severe bronchial
      asthmatic attacks as well as chronic obstructive pulmonary disease.

PMID- 11300147
TI  - Susac's syndrome: beneficial effects of corticosteroid therapy in a Japanese
      case.
AB  - Susac's syndrome is a rare disorder characterized by the triad of microangiopathy
      of the brain and retina with hearing loss. More than 50 affected individuals have
      been reported worldwide, all Caucasians. We herein identify the first Japanese
      patient with Susac's syndrome. A 36-year-old man developed recurrent subacute
      encephalopathy, bi- a lateral sensorineural hearing loss, and retinal arteriolar
      occlusions, caused by microangiopathy from a year previously. T2-weighted MRI
      showed multiple high-signal lesions ti predominantly in the periventricular white
      matter. During the exacerbated phase both high-dose intravenous methyl
      prednisolone and oral prednisone therapy produced beneficial effects. He showed
      definite remission within 2 years from the disease onset.

PMID- 11300148
TI  - A patient with severe palindromic rheumatism and frequent episodes of pain.
AB  - A 44-year-old man began to experience episodes of joint pain with erythema in his
      knees, elbows, shoulders, and hands in April 1996. He was diagnosed as having
      palindromic rheumatism. Due to the increasing frequency and severity of these
      episodes, he was admitted to our hospital in May 1999. Heat therapy to the
      affected area produced a rapid improvement in symptoms. In addition, the
      continued use of physical therapy during symptom-free periods tended to reduce
      the frequency and severity of pain attacks. We present this case and discuss
      treatment options in patients with palindromic rheumatism.

PMID- 11300149
TI  - Symposium on the etiology of hypertension--summarizing studies in 20th century.
      1. Hypertension and genes.
AB  - Under classical strategy, scientists have tried first to find a physiological
      phenomenon specific for essential hypertension, then to identify the protein
      underlying the physiological abnormality, and finally to clarify the causative
      gene which encoded the protein. On the other hand, under the reverse genetic
      approach, the correlation between hypertension and genetic abnormality is
      identified first, and then the pathogenesis is clarified-in reverse order.
      Therefore, it is not extraordinary for unexpected results to be obtained in the
      correlation between a gene and a disease, suggesting that this approach has a
      possibility to be a breakthrough in the chaos of hypertension research.

PMID- 11300150
TI  - Symposium on the etiology of hypertension--summarizing studies in 20th century.
      2. Genetic engineering in hypertension research.

PMID- 11300151
TI  - Symposium on the etiology of hypertension--summarizing studies in 20th century.
      3. The sympathetic nervous system in essential hypertension: pathophysiological
      significance.

PMID- 11300152
TI  - Symposium on the etiology of hypertension--summarizing studies in 20th century.
      4. Pathogenesis of hypertension--kidney as a pathogenetic organ of hypertension.

PMID- 11300153
TI  - Symposium on the etiology of hypertension--summarizing studies in 20th century.
      5. Renin-angiotensin system and hypertension.

PMID- 11300155
TI  - Symposium on molecular pathogenesis of respiratory diseases and its clinical
      implication. 2. Obstructive lung disease.

PMID- 11300154
TI  - Symposium on molecular pathogenesis of respiratory diseases and its clinical
      implication. 1. Diffuse infiltrative lung disease--new clinical biomarker in
      diffuse interstitial pneumonia.

PMID- 11300156
TI  - Symposium on molecular pathogenesis of respiratory diseases and its clinical
      implication. 3. Immunological lung disease--recent advances in the pathogenesis
      of hypersensitivity pneumonitis.

PMID- 11300157
TI  - Symposium on molecular pathogenesis of respiratory diseases and its clinical
      implication. 4. Molecular pathogenesis of lung cancer and its molecular targeted
      therapy.

PMID- 11300158
TI  - Symposium on molecular pathogenesis of respiratory diseases and its clinical
      implication. 5. Respiratory tract infection.

PMID- 11300159
TI  - Symposium on clinical aspects in hepatitis virus infection. 1. Hepatitis viruses
      update.

PMID- 11300160
TI  - Symposium on clinical aspects in hepatitis virus infection. 2. Recent advances in
      acute and fulminant hepatitis in Japan.

PMID- 11300161
TI  - Symposium on clinical aspects in hepatitis virus infection. 3. Update of liver
      disease related to chronic hepatitis B virus infection.

PMID- 11300162
TI  - Symposium on clinical aspects in hepatitis virus infection. 4. Topics of type C
      chronic liver disease.

PMID- 11300163
TI  - Symposium on clinical aspects in hepatitis virus infection. 5. Clinical practice
      of hepatitis: myocardial diseases, nephritis, and vasculitis associated with
      hepatitis virus.

PMID- 11300164
TI  - Symposium on clinical aspects in hepatitis virus infection. 6. Hepatitis virus
      and extrahepatic manifestions--skin, mucosa, muscle, and hematopoietic organs.

PMID- 11300165
TI  - Allergy and angiitis: two aspects of Churg-Strauss syndrome.

PMID- 11300166
TI  - Hepatitis C virus and cardiomyopathy.

PMID- 11300167
TI  - Retroviruses and autoimmunity.
AB  - The investigation of human retroviruses has shown dramatic progress since the
      discovery of human immunodeficiency virus (HIV). These studies have also
      contributed to the exploration of the role of retroviruses, including endogenous
      retroviruses, in the induction of autoimmune diseases such as systemic lupus
      erythematosus (SLE). This review describes the potential role of retroviruses in
      autoimmunity, based on recent findings including our own results.

PMID- 11300168
TI  - Current status and future of lung transplantation.
AB  - Lung transplantation has been performed successfully outside Japan since 1983 in
      patients with end-stage lung disease. More than 9,000 lung transplants have been
      reported in The Registry of the International Society for Heart and Lung
      Transplantation. In contrast, a transplant law became effective in Japan only
      recently, and four universities were designated as official lung transplant
      centers (Okayama, Osaka, Kyoto and Tohoku Universities). In October 1998, the
      first successful living-donor lobar lung transplantation was performed at Okayama
      University. Since then, seven lung transplants (four from living donors and three
      from cadaveric donors) have been successfully performed in Japan. Although lung
      transplantation offers acceptable prospects for 5-year survival, chronic
      rejection and donor shortage remain to be major problems. In an effort to address
      the donor shortage issue, living-donor lobar lung transplantations have been
      performed with satisfactory intermediate survival and functional results.

PMID- 11300169
TI  - Epstein-Barr virus-associated gastric cancer in a patient with dermatomyositis.
AB  - A 59-year-old man was admitted presenting systemic rash and muscle weakness. He
      was diagnosed to have dermatomyositis and a check was made for internal
      malignancy. Gastrointestinal endoscopy revealed a Borrmann type II tumor on the
      middle body of the stomach. Biopsy specimens showed a well differentiated
      adenocarcinoma, and total gastrectomy was performed. The final diagnosis was
      moderately differentiated adenocarcinoma invading into the proper muscular layer,
      with metastases to regional lymph nodes. Most of the neoplastic cells were shown
      to be positive for Epstein-Barr virus by means of EBV-encoded RNA in situ
      hybridization. The symptoms of dermatomyositis disappeared completely after
      surgery.

PMID- 11300170
TI  - Acculturation and dental health among Vietnamese living in Melbourne, Australia.
AB  - OBJECTIVES: To describe the relationship between acculturation and oral health
      status, oral health knowledge and frequency of dental visits in subjects of
      Vietnamese background, 18 years or older, living in Melbourne, Australia.
      METHODS: Oral health status was measured using the DMFS index. Oral health
      knowledge was estimated by responses to six specific oral preventive measures:
      brushing, flossing, use of fluorides, diet, and dental visits. Dental visits was
      measured by the number of visits in the 12 months prior to the survey.
      Acculturation was measured along two dimensions, psychological and behavioural,
      using the Psychological-Behavioural Acculturation Scale. Data were analysed using
      multivariate analysis to identify the combined effect of eight predictors (age,
      gender, occupational status, education, reason for migration, proportion of life
      in the host country, behavioural acculturation and psychological acculturation)
      against the dependent variables. RESULTS: The analysis was conducted on a sample
      of 147 subjects and showed significant interactions between the acculturation
      variables and three outcome measures: dental caries, knowledge of preventive
      measures and dental visits. Results indicated that acculturation was an important
      intervening variable. Psychological acculturation was strongly related to the
      three oral health outcomes, although the effect of behavioural acculturation was
      also apparent regarding dental status. CONCLUSIONS: This study offers several
      insights for understanding the mechanisms by which acculturation impacts oral
      health status. Interventions that simplify the cultural influence of immigrant
      groups by focusing on socio-demographic differences and even immigration
      variables to define risk groups might not produce predicted changes in oral
      health status.

PMID- 11300171
TI  - Quantifying the diffused benefit from water fluoridation in the United States.
AB  - OBJECTIVE: To estimate the total contribution of water fluoridation to caries
      reduction by including the benefit from the diffusion of fluoride from
      fluoridated communities to surrounding nonfluoridated communities via the export
      of bottled beverages and processed foods. METHODS: We analyzed data from the 1986
      87 NIDR Children's Survey for 18,507 school children aged 6-17 years who had at
      least one permanent tooth and for whom a complete fluoride exposure history could
      be created. To measure water fluoridation exposure, we generated continuous and
      categorical exposure variables. Years of fluoridation exposure (YFE-continuous)
      measured the number of years the child lived at residences receiving fluoridated
      water. Lifetime fluoridation exposure (LFE-categorical) was high if the child
      lived at residences receiving fluoridated water more than 50% of his life and
      low, otherwise. We summed the proportion of state population receiving
      fluoridated water times the number of years the child had lived in each state and
      then divided this value by the child's age to measure diffusion exposure (DE). We
      grouped DE into three levels: low (DE<=0.25), medium (0.25<DE<0.55), and high
      (DE>=0.55). For each level of DE, we compared the age-adjusted mean DMFS for high
      and low LFE. In addition we used linear regression to measure the association
      between DMFS and YFE while controlling for DE, age, exposures to other fluoride
      sources, and sociodemographic variables. Reported results are significant at
      P<0.05. RESULTS: Comparison of mean DMFS scores found that the direct benefit of
      water fluoridation (DMFS(LFE=low) - DMFS(LFE=high)) was 1.44 surfaces among low
      DE children and 0 among high DE children. The diffused benefit (DMFS(LFE=low,
      DE=low) - DMFS(LFE=low, DE=high)) was 1.23 surfaces. The regression results were
      similar and indicated that the direct benefit would be 1.44 fewer DMFS for low DE
      children and the indirect benefit would be 1.09 fewer DMFS for high DE children.
      CONCLUSION: Failure to account for the diffusion effect may result in an
      underestimation of the total benefit of water fluoridation, especially in high
      diffusion exposure regions.

PMID- 11300172
TI  - Smoking in adolescence as a predictor of early loss of periodontal attachment.
AB  - OBJECTIVES: On the basis of information from studies of older adults, smoking is
      considered to be an important risk factor for periodontal disease. Examining
      periodontal loss of attachment among younger adults means a lower contribution
      from cumulative exposure to other environmental risk factors. The aim of this
      study was to examine the role of chronic exposure to cigarette smoking as a risk
      factor for greater prevalence and extent of periodontal loss of attachment among
      26-year-old participants in a longstanding prospective cohort study. METHODS:
      Loss of attachment (LOA) was measured at three sites per tooth in two randomly
      selected contralateral quadrants (one upper, one lower). Cigarette smoking
      history was obtained at ages 15, 18, 21 and 26, and used to categorise
      participants as "never-smokers", "ever-smokers", "long-term smokers" or "very
      longterm smokers". RESULTS: Periodontal data were available for 914 Study
      members, among whom the prevalence of LOA of 4+mm was 19.4%. Among those who
      smoked at ages 15, 18, 21 and 26, it was 33.6%, and, after controlling for sex,
      selfcare and dental visiting, they were nearly three times as likely to have one
      or more sites with 4+mm LOA. CONCLUSIONS: Chronic exposure to smoking is a strong
      predictor of periodontal disease prevalence in young adults.

PMID- 11300173
TI  - A prospective study on sucrose consumption, visible plaque and caries in children
      from 3 to 6 years of age.
AB  - OBJECTIVES: As data on the association of sugar consumption and dental caries in
      the industrialized countries give mixed results, we prospectively studied this
      association in 135 healthy Finnish children (71 boys, 64 girls). METHODS: The
      dental health and oral hygiene of the children was first examined at the mean age
      (+/-SD) of 37.4 (+/-2.1) months and again at 73.7 (+/-2.6) months. On both
      occasions the parents were interviewed about the child's sweet intake and
      toothbrushing habits, and sucrose consumption was analyzed using 4-day food
      diaries. RESULTS: The proportion of children with caries experience, enamel and
      dentin lesions combined, increased from 16% to 40%. Daily sucrose intake of
      children who developed caries by 6 years of age, whether expressed as absolute
      (g) or as relative (E%) amounts, was already higher at 3 years of age than that
      of children who stayed caries-free (P<0.05 and P<0.03, respectively).
      Furthermore, children who used sweets more than once a week at 3 years of age,
      consumed more sucrose 3 years later (P<0.01) than those who used sweets once a
      week or less. The proportion of children with a combination of a sweet intake
      more than once a week and visible plaque, increased (P<0.05) during the follow
      up. The risk ratio of children with the combined risk habit at 3 years of age to
      develop carious lesions by 6 years of age was 1.7 compared to the rest of the
      children (95% confidence interval 0.9-3.0). CONCLUSIONS: We conclude that the
      manifestation of dental caries at 6 years of age seemed to be associated with a
      higher daily sucrose intake that had started already at 3 years of age. Moreover,
      a combination of sweet intake more than once a week and visible plaque at 3 years
      of age may be predictive of dental health 3 years later.

PMID- 11300174
TI  - Effectiveness of the school dental screening programme in stimulating dental
      attendance for children in need of treatment in Northern Ireland.
AB  - The school dental screening programme has been in existence from the beginning of
      the 20th century yet its value in encouraging attendance among children with a
      dental health need is not fully established. OBJECTIVE: To evaluate the
      effectiveness of school dental screening in promoting dental attendance among
      children with a treatment need and to examine the relative importance of
      screening, social class and other factors in dental attendance. METHODS: Sixty
      four participating schools were assigned to study and control groups using a
      stratified, blocked randomisation technique. The study group children received
      the standard school dental screening and the dental attendance of those with a
      positive screening result was assessed after 2 months by means of a questionnaire
      issued to the children's parents. The control group children were not, at this
      stage, screened, yet their parents received the same questionnaire assessing
      dental attendance over the 2-month period. However, only questionnaires from
      control group children who had a positive result at a subsequent screening were
      retained for analysis. RESULTS: A total of 2,321 children were screened, with 980
      having a positive result. The mean dmft of those screening positive was 4.85. In
      all, 664 completed questionnaires were returned, giving a response rate of 67.8%.
      Dental attendance was reported among 45.5% of the study group (n=352) in the 2
      months following screening. In the same period, 27.6% of the control group
      (n=312) claimed attendance. The effect was found to be significant among the high
      employed group (P<0.01) and the unemployed group (P<0.05). CONCLUSION: School
      dental screening was capable of stimulating dental attendance. The strong effect
      among the lowest socio-economic group shows that school dental screening may be
      used to decrease dental health inequalities.

PMID- 11300175
TI  - Direct and indirect costs of dental trauma in Sweden: a 2-year prospective study
      of children and adolescents.
AB  - OBJECTIVES: To study total costs, including direct costs (health care service,
      loss of personal property, medicine and transport) and indirect costs (loss of
      production or leisure) of dental trauma to children and adolescents with special
      reference to predictors. METHODS: The study was based on a random sample of 192
      children and adolescents with a dental trauma reported to an insurance company
      and prospectively followed up by telephone interviews over a period of 2 years.
      RESULTS: On average, health care service costs represented 2,955 SEK (SD=3,818)
      and total costs 4,569 SEK (SD=3,053) for dental trauma to permanent teeth, and
      837 SEK (SD=898) and 1,746 SEK (SD=1,183) for trauma to primary teeth. The most
      extensive type of indirect cost was loss of production or leisure, which averaged
      1,286 SEK (SD=1,830) for injuries to permanent teeth and 699 SEK (SD=1,239) for
      injuries to primary teeth. Multiple regression analysis of demographic and dental
      injury variables showed that complicated trauma was of special importance to
      costs for permanent and primary teeth injuries. The average relative increase in
      total costs to patients and companions for complicated injury to permanent teeth
      was 140% (95% confidence interval [CI], 66-248%) for patients and 132% (95% CI,
      54-249%) for companions. Lack of access to a dental clinic near the place of
      residence could increase the average total costs of injuries to permanent teeth
      by 91% for companions (95% CI, 20-204%) and for primary teeth by 134% (95% CI, 38
      296%). CONCLUSIONS: Dental traumas result in both direct and indirect costs, with
      a predominance of direct costs. The direct costs primarily depend on degree of
      severity, while indirect costs are mostly due to compromised access to health
      care service. Traumas to permanent teeth are especially costly and, due to
      additional maintenance, the care may continue for several years. This study has
      drawn attention to the significant implications of dental trauma to patient and
      companion, a new area where further studies are warranted.

PMID- 11300176
TI  - A proposed method for assessing the quality of sealants--the CCC Sealant
      Evaluation System.
AB  - OBJECTIVES: The aim of this paper is to introduce the C (colour) C (coverage) C
      (caries) Sealant Evaluation System and to present results of its use on a sample
      of adolescent patients in Scotland. METHODS: Baseline data are presented from a 3
      year prospective study in general dental practices across Scotland. Subjects were
      examined under standardised conditions by one trained and calibrated examiner.
      RESULTS: 78.6% of the subjects had one or more sealed teeth, over half of these
      sealants being judged inadequate. There was a low prevalence of dentine caries
      associated with the sealed teeth (2.8%). The CCC sealant Evaluation System proved
      practical as demonstrated by its use during the project and had substantial intra
      examiner reproducibility. CONCLUSIONS: There was a high level of sealant
      provision; however, this provision may not be optimal in terms of both targeting
      of provision and sealant maintenance. The CCC sealant Evaluation System appeared
      to be a useful assessment tool for assessing sealed surfaces.

PMID- 11300177
TI  - Use of a national database for strategic management of municipal oral health
      services for Danish children and adolescents.
AB  - OBJECTIVE: To evaluate the use of a national register for strategic management of
      dental health services for 0-17-year-old Danish children and to identify
      determinants for their use of the system as a strategic tool in management of the
      services. METHODS: During the period December 1997 to January 1998, the leaders
      of 268 private and public dental services were mailed a self-administered postal
      questionnaire on their use of the dental health reporting system of the Danish
      National Board of Health, the so-called SCOR-system. Ninety-six percent
      responded. The questionnaire contained questions about the use of SCOR (dependent
      variable) and the following independent variables: 1) the dental service in the
      municipality; and 2) the leader of the dental service, including his/her
      assessment of and knowledge related to the SCOR-system. Information concerning
      other independent variables such as: 1) the population and the socio-economic,
      cultural and political environment of the municipality; and 2) dental morbidity
      was collected as antecedent data from various official sources. RESULTS: Seventy
      seven percent of municipalities with public clinics and 68% of municipalities
      without public clinics used SCOR-tables for planning purposes and preventive
      intervention. Forty percent reported data for all age groups to the SCOR-system
      and 36% used non-obligatory special codes in order to monitor more specific
      questions. Use of SCOR data was positively associated with the dental health
      services being organized in public clinics, with a high number of public clinics
      in the municipality, and with a positive assessment among the dental leaders of
      the reporting system as a planning tool. Special codes for precavitated lesions
      and/or fissure sealants were used more frequently in municipalities where DMFS in
      15-year-olds had decreased from 1995 to 1996. Otherwise no associations between
      dental health and use of the system could be demonstrated. CONCLUSIONS: SCOR is
      widely used as a strategic planning instrument concerning the Danish dental
      services for children and adolescents. The predictors associated with its use are
      partly structural characteristics of the municipality and its dental service and
      factors partly related to a leader's knowledge about and assessment of the
      system. These factors might be amenable to change through training of the users
      of the system.

PMID- 11300178
TI  - Self-perceived oral health among three subgroups of Asian-Americans in New York
      City: a preliminary study.
AB  - OBJECTIVES: The aim of this preliminary study was to compare the perception of
      oral health among subgroups of Asian-American residents of New York City, USA.
      METHODS: A close-ended questionnaire was administered to 255 Chinese, 134 Indian
      and 84 Pakistani adults, aged 18-65 years, during 1994-95. A comprehensive dental
      and oral examination was also performed. The associations of demographic and oral
      health variables with perceived oral health were evaluated using multivariate
      ordinal regression models. RESULTS: When data were analyzed in a multivariate
      context, only ethnicity and income were significant predictors of perceived oral
      health, after adjusting for DMFT. The within-group multivariate analysis of the
      three ethnic subgroups' results were as follows: Among the Chinese there were no
      significant predictors, only income was strongly suggestive; among the Indians,
      number of missing teeth and number of years in the USA were significant
      predictors; and within the Pakistani group, DMFT was the only significant
      predictor. CONCLUSIONS: Results suggest that there are ethnic differences in the
      perception of oral health status even after adjusting for clinical variables as
      well as for demographic variables in this particular group of Asian-American
      residents of New York City. Predictors associated with the perception of oral
      health are different for each ethnic group. When designing oral health promotion
      activities to diverse ethnic groups, the cultural characteristics of each
      subgroup should be considered.

PMID- 11300179
TI  - Trends in community violence in England and Wales 1995-1998: an accident and
      emergency department perspective.
AB  - OBJECTIVES: To identify overall, seasonal, sex and age specific national trends
      in community violence from an accident and emergency (A&E) department
      perspective. DESIGN AND SETTING: Prospective collection of national violence data
      from a stratified random sample of 33 A&E departments in England and Wales.
      METHODS: Data were analysed for the three years from May 1995 to April 1998. Time
      series statistical methods were used to detect trends among those aged 0-10, 11
      17, 18-30, 31-50 and 51 + years. RESULTS: 121475 assaults were identified: 89533
      (74%) men sustained injury. Forty five per cent were aged 18-30. The significant
      trends were an increase in injured women and those aged 31-50. Significant
      seasonal trends were identified for both sexes and all age groups: peaks were
      found in July to September and troughs in February to April. CONCLUSIONS: There
      was no overall significant change in levels of violence between 1995-1998 from an
      A&E department perspective. Numbers of women injured and those aged 31-50
      increased significantly. The incidence of injury sustained in community violence
      is biphasic: is highest during July to September and lowest during February to
      April. National A&E department violence surveillance provides a unique
      perspective.

PMID- 11300180
TI  - The association between deprivation levels, attendance rate and triage category
      of children attending a children's accident and emergency department.
AB  - OBJECTIVE: To determine the relation between deprivation category, triage score
      and accident and emergency (A&E) attendance for children under the age of 13.
      DESIGN: Retrospective study of all children attending an A&E department over one
      year. SETTING: A paediatric teaching hospital in Edinburgh. SUBJECTS: All
      children attending the A&E department who had a postcode and a triage score
      documented on attendance. The postcode was used to determine the deprivation
      category and the triage scored the severity of illness or injury. MAIN OUTCOME
      MEASURE: The relation between deprivation category, triage score and frequency of
      attendance. RESULTS: There is a trend towards increased attendance in all triage
      categories for deprivation categories 6 and 7. CONCLUSIONS: Attendance at A&E is
      not only related to severity of injury but also to deprivation category. The
      reason why people from disadvantaged areas attend more frequently needs further
      evaluation.

PMID- 11300181
TI  - Comparing two different methods of identifying alcohol related problems in the
      emergency department: a real chance to intervene?
AB  - OBJECTIVES: To examine the feasibility of screening for alcohol problems in a
      representative flow sample of patients attending a busy UK emergency department.
      To compare two methods of identifying alcohol related problems in the emergency
      department. METHODS: Brief interview administered by the same interviewer to a
      representative flow sample of 429 patients attending a single accident and
      emergency department over a six week period. Measures included a CAGE
      questionnaire and assessments by the patient and staff as to whether the
      attendance was alcohol related. RESULTS: 413 patients (96%) were successfully
      screened. Of these, 115 (28%) patients were considered to have an alcohol related
      attendance on the basis of the CAGE questionnaire or the staff assessment. Head
      injuries and psychiatric presentations were particularly likely to be associated
      with alcohol misuse. Compared with those identified by staff, patients scoring
      above threshold on the CAGE were more likely to attend during routine working
      hours and recognise they had an alcohol problem. CONCLUSIONS: Emergency
      departments may provide an opportunity for the early prevention of alcohol
      related difficulties. However, patients with alcohol problems who present to the
      emergency department are not a homogenous group. Different screening methods
      identify different groups of patients, who in turn may respond to different forms
      of intervention. Further research examining the efficacy and feasibility of
      different alcohol treatment approaches is needed to enable us to target specific
      interventions to those patients who might most benefit.

PMID- 11300182
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Lorazepam or diazepam for generalised convulsions in adults.

PMID- 11300183
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Capillary blood gases in COPD.

PMID- 11300184
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Salbutamol and ipratropium in COPD.

PMID- 11300185
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Nebulised epinephrine or corticosteroids in croup.

PMID- 11300186
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Prophylactic magnesium in myocardial infarction.

PMID- 11300187
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. SimpliRed and diagnosis of deep venous thrombosis.

PMID- 11300188
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Monophasic or biphasic defibrillation.

PMID- 11300189
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Antibiotics for otitis media.

PMID- 11300190
TI  - Article 6. An introduction to hypothesis testing. Parametric comparison of two
      groups--1.

PMID- 11300191
TI  - Article 1. Introduction--St Jude's, the "virtual" A&E department.
AB  - Management is part of everyday life in emergency care. This project will
      hopefully bring alive management issues, give a "real" framework to assist the
      discussion of management theory and hopefully to entertain. We look forward to
      your feedback on the tasks and welcome ideas on how the St Jude's should go
      forward.

PMID- 11300192
TI  - Clostridium novyi infection: a fatal association with injecting drug users.
AB  - Injecting drug users frequently use accident and emergency (A&E) departments to
      access emergency care for local and systemic infections. Clostridium novyi type A
      is a bacterium that has recently been associated with a number of fatalities
      among drug injecting addicts. The clinical course is described of a patient who
      attended an A&E department with septicaemia who was found at postmortem
      examination to have been infected with Clostridium novyi type A. Doctors working
      in A&E departments should be aware of the existence of this infection and be
      vigilant when treating injecting drug users with localised infection.

PMID- 11300193
TI  - An uncommon cause of foot ulcer: tuberculosis osteomyelitis.
AB  - Tuberculous osteomyelitis is an uncommon infection that usually involves the
      vertebrae. An otherwise healthy young man with a chronic discharging sinus on his
      right foot caused by tuberculous osteomyelitis is described. The risk factors,
      clinical features, radiological findings, and investigations of tuberculous
      osteomyelitis are briefly reviewed. Tuberculous osteomyelitis usually runs an
      insidious course; emergency physicians should be aware of the possibility of
      tuberculous osteomyelitis especially when patients present with chronic
      unexplained musculoskeletal symptoms.

PMID- 11300194
TI  - Emergency presentation of oesophageal carcinoma. An unusual case.

PMID- 11300195
TI  - Acute myelogenous leukaemia presenting with mid-foot pain after an inversion
      injury.
AB  - The case is presented of a 5 year old boy who attended after an inversion injury.
      He had persistent pain despite treatment and was subsequently diagnosed with
      acute myelogenous leukaemia. It is well recognised that acute leukaemia commonly
      presents as non-traumatic limb pain. This case highlights the need to consider
      acute leukaemia in the differential diagnosis of any persisting bone or joint
      pain, even in the context of recent injury.

PMID- 11300196
TI  - Bilateral spontaneous pneumothorax--the case for prompt chest radiography.

PMID- 11300197
TI  - A misdiagnosed fracture of the calcaneum.

PMID- 11300198
TI  - Pancreatic trauma in a child.

PMID- 11300199
TI  - Toxicological screening in trauma.

PMID- 11300201
TI  - Chest pain observation units.

PMID- 11300200
TI  - The Ottawa ankle rule.

PMID- 11300202
TI  - Chest pain observation units.

PMID- 11300203
TI  - Three generations of recurrent dislocated shoulders.

PMID- 11300204
TI  - Emergency medicine terminology in the United Kingdom--time to follow the trend?
AB  - OBJECTIVE: To determine the frequency of use of the terms "accident and
      emergency" and "emergency medicine" and their derivatives in original articles in
      the Journal of Accident and Emergency Medicine. METHODS: Hand search of all
      articles in the Journal of Accident and Emergency Medicine from September 1995 to
      July 2000, categorising the first use of terminology in each original article to
      describe the specialty, its departments, or their staff into either accident and
      emergency or emergency medicine groups. RESULTS: There is a clear trend towards
      increasing use of the terms emergency medicine, emergency physician and emergency
      department, with decreasing use of the terms accident and emergency medicine,
      accident and emergency department and accident and emergency doctor, although the
      latter group still constitutes the majority. CONCLUSION: The use of emergency
      medicine to describe the specialty in the United Kingdom is increasing, although
      this may reflect the Journal's growing international standing. This trend should
      be taken into account in the debate over the specialty's name in this country.

PMID- 11300206
TI  - Emergency airway management by non-anaesthesia house officers--a comparison of
      three strategies.
AB  - OBJECTIVES: The purpose of this study was to determine effects of different
      airway devices and tidal volumes on lung ventilation and gastric inflation in an
      unprotected airway. METHODS: Thirty one non-anaesthesia house officers
      volunteered for the study, and ventilated a bench model simulating an unintubated
      respiratory arrest patient with bag-valve-facemask, laryngeal mask airway, and
      combitube using paediatric and adult self inflating bags. RESULTS: The paediatric
      versus adult self inflating bag resulted with the laryngeal mask airway and
      combitube in significantly (p<0.001) lower mean (SEM) lung tidal volumes (376
      (30) v 653 (47) ml, and 368 (28) v 727 (53) ml, respectively). Gastric inflation
      was zero with the combitube; and 0 (0) v 8 (3) ml with the laryngeal mask airway
      with low versus large tidal volumes. The paediatric versus adult self inflating
      bag with the bag-valve-facemask resulted in comparable lung tidal volumes (245
      (19) v 271 (33) ml; p=NS); but significantly (p<0.001) lower gastric tidal volume
      (149 (11) v 272 (24) ml). CONCLUSIONS: The paediatric self inflating bag may be
      an option to reduce the risk of gastric inflation when using the laryngeal mask
      airway, and especially, the bag-valve-facemask. Both the laryngeal mask airway
      and combitube proved to be valid alternatives for the bag-valve-facemask in this
      experimental model.

PMID- 11300205
TI  - The therapeutic potential of regulated hypothermia.
AB  - Reducing body temperature of rodents has been found to improve their survival to
      ischaemia, hypoxia, chemical toxicants, and many other types of insults. Larger
      species, including humans, may also benefit from a lower body temperature when
      recovering from CNS ischaemia and other traumatic insults. Rodents subjected to
      these insults undergo a regulated hypothermic response (that is, decrease in set
      point temperature) characterised by preference for cooler ambient temperatures,
      peripheral vasodilatation, and reduced metabolic rate. However, forced
      hypothermia (that is, body temperature forced below set point) is the only method
      used in the study and treatment of human pathological insults. The therapeutic
      efficacy of the hypothermic treatment is likely to be influenced by the nature of
      the reduction in body temperature (that is, forced versus regulated). Homeostatic
      mechanisms counter forced reductions in body temperature resulting in
      physiological stress and decreased efficacy of the hypothermic treatment. On the
      other hand, regulated hypothermia would seem to be the best means of achieving a
      therapeutic benefit because thermal homeostatic systems mediate a controlled
      reduction in core temperature.

PMID- 11300207
TI  - Carbon monoxide poisoning: correlation of neurological findings between accident
      and emergency departments and a hyperbaric unit.
AB  - OBJECTIVES: To investigate and quantify the differences in neurological
      examination findings in patients acutely poisoned with carbon monoxide, between
      initial assessment at accident and emergency (A&E) departments and subsequently
      at a hyperbaric unit. METHODS: Retrospective case note review of all patients
      referred to the Hull Hyperbaric Unit for treatment of acute carbon monoxide
      poisoning between August 1998 and August 1999. Patients who were ventilated or
      less than 16 years old were excluded because of difficulty in assessing their
      neurological status. RESULTS: Thirty patients were included for analysis. The
      mean duration from exposure to assessment in A&E was four hours while patients
      were reviewed on average three hours later at the hyperbaric unit. Referrals came
      from 14 different hospitals. A history of loss of consciousness accounted for 70%
      of referrals. A mean of 3.2 neurological signs per patient was documented in A&E
      compared with 9.2 at the hyperbaric unit. Seventy nine per cent of abnormal
      neurological signs were not detected at A&E departments compared with 3% at the
      hyperbaric unit. The major source of discrepancy was in sharpened Rhomberg's test
      and heel-toe gait, in 13% of patients examined in A&E departments these signs
      were recorded as abnormal compared with 90% at the hyperbaric unit. CONCLUSION:
      There is a large discrepancy in neurological findings between assessment in A&E
      departments and the Hull Hyperbaric Unit. A number of factors may account for
      this including interobserver variation, patient deterioration during transfer,
      poor documentation, lack of understanding of the sequelae of carbon monoxide
      poisoning and inadequate examinations. Further research is required to quantify
      the impact of the various factors that may contribute to the differences in
      neurological findings.

PMID- 11300209
TI  - Agents acting and moving in healthcare scenario--a paradigm for telemedical
      collaboration.
AB  - This communications describes a novel approach to the analysis and development of
      telemedicine systems, based on the multiagent paradigm. An agent is an
      autonomous, social, reactive, and proactive entity, sometimes also mobile. Since
      telemedicine is grounded on communication and sharing of resources, agents are
      suitable for its analysis and implementation, and we adopted them for developing
      a prototype telemedical agent.

PMID- 11300210
TI  - Design of a telemedicine system using a mobile telephone.
AB  - This paper describes the design of a prototype integrated mobile telemedicine
      system that is compatible with existing mobile telecommunications networks and
      upgradable for use with third-generation networks. The system, when fully
      developed, will enable a doctor to monitor remotely a patient who is free to move
      around for sports medicine and for emergency situations.

PMID- 11300208
TI  - Improving detection of alcohol misuse in patients presenting to an accident and
      emergency department.
AB  - OBJECTIVES: To assess and improve deployment of a brief test for alcohol misuse:
      the Paddington Alcohol Test (PAT). Design-Prospective study of the effects of
      audit feedback. SETTING: An urban accident and emergency department. SUBJECTS:
      Senior house officers (SHO) (n = 13). OUTCOME MEASUREMENTS: PAT use and
      categorisation of patients for each SHO; observational analysis of presenting
      complaints according to PAT. RESULTS: 1062 of 1737 patients (61.1%) were defined
      as PAT possible-that is, presented with > or = one complaint listed on the PAT
      test proforma. In month 1, PAT uptake was poor. PAT use improved significantly
      when feedback was instituted (p<0.0001). The response to audit and feedback
      showed marked inter-SHO variation. When feedback was withdrawn (month 4), there
      was a significant reduction in PAT use (p=0.003). Three other indices of
      detection followed this trend: (a) number of PAT positive patients identified,
      (b) proportion of PAT possible patients identified as PAT positive, and (c)
      number of PAT positive patients referred to the alcoholic health worker. The 10
      most common PAT positive categories, accounting for 77% of all PAT positive
      complaints were: fall > collapse (including "fit", "blackout") > head injury
      (including "facial injury") > assault (including "domestic violence" and 'other')
      > nonspecific gastrointestinal problem > "unwell" > psychiatric (including
      "depression", "overdose", "confusion") > cardiac (including "chest pain" and
      "palpitations") > self neglect > repeat attendance. CONCLUSIONS: Ongoing audit
      with feedback improves both PAT use and detection of alcohol misuse. The PAT is
      now simpler including only 10 conditions, which should further aid its use.

PMID- 11300211
TI  - A telematic system for oncology based on electronic health and patient records.

PMID- 11300212
TI  - A 3-D marker-free system for the analysis of movement disabilities--an
      application to the legs.
AB  - The aim of this paper is to describe an approach allowing the analysis of human
      motion in three-dimensional (3-D) space. The system that we developed is composed
      of three charge-coupled-device cameras that capture synchronized image sequences
      of a human body in motion without the use of markers. Characteristic points
      belonging to the boundaries of the body in motion are first extracted from the
      initial images. Two-dimensional superquadrics are then adjusted on these points
      by a fuzzy clustering process. After that, the position of a 3-D model based on a
      set of articulated superquadrics, each of them describing a part of the human
      body, is reconstructed. An optical flow process allows the prediction of the
      position of the model from its position at the previous time, and gives initial
      values for the fuzzy classification. The results that we present concern more
      specifically the analysis of movement disabilities of a human leg during gait.
      They are improved by using articulation-based constraints. The methodology can be
      used in human motion analysis for clinical applications.

PMID- 11300213
TI  - Telemedicine system using computed tomography van of high-speed telecommunication
      vehicle.
AB  - The current medical system provides medical services to patients who visit
      hospitals. However, medical services can be provided at or close to the home of
      the patient using fully equipped mobile telemedicine systems. Such a system can
      identify the disease at an early stage, improve quality of life and prognosis
      through early diagnosis and treatment, and reduce the costs of medical service.
      Furthermore, the unit can provide mass screenings of the population, as well as
      full medical service to remote areas. The Telecommunications Advanced
      Organization of Japan, Matsumoto, Japan, and Shinshu University Hospital,
      Matsumoto, Japan, established a research center for a unique telemedicine project
      using a mobile system. The mobile unit consists of a van that houses a spiral
      computed-tomography (CT) machine and various telecommunications equipment. The
      unit allows medical examination, CT scanning, and on-line two-way transfer of
      image data/teleconferencing to a medical center for consultation with various
      specialists. We have used the system thus far for the early detection of lung
      cancer through mass screenings over a four-year period in 29 administrative
      districts. Mass screenings of 19117 residents resulted in the identification of
      75 cases of early lung cancer who were later treated by partial pneumonectomy at
      Shinshu University Hospital and affiliated hospitals. We have also used the
      system to provide medical services to rural areas, as telemedicine support at
      remote areas, wintertime telemedicine support to an international sports
      competition, and various medical services to a home-care facility.

PMID- 11300214
TI  - Abstracting human control strategy in projecting light source.
AB  - In this paper, we present a method of modeling human strategy in controlling a
      light source in a dynamic environment. We take a simple example of how to control
      the light source to avoid a shadow and maintain appropriate illumination
      conditions on the target area of attention to illustrate the procedure and
      method. This work is valuable to various applications of automatic light control
      from surgical room and space applications to inspections.

PMID- 11300215
TI  - A knowledge-based system for patient image pre-fetching in heterogeneous database
      environments--modeling, design, and evaluation.
AB  - When performing primary reading on a newly taken radiological examination, a
      radiologist often needs to reference relevant prior images of the same patient
      for confirmation or comparison purposes. Support of such image references is of
      clinical importance and may have significant effects on radiologists' examination
      reading efficiency, service quality, and work satisfaction. To effectively
      support such image reference needs, we proposed and developed a knowledge-based
      patient image pre-fetching system, addressing several challenging requirements of
      the application that include representation and learning of image reference
      heuristics and management of data-intensive knowledge inferencing. Moreover, the
      system demands an extensible and maintainable architecture design capable of
      effectively adapting to a dynamic environment characterized by heterogeneous and
      autonomous data source systems. In this paper, we developed a synthesized object
      oriented entity- relationship model, a conceptual model appropriate for
      representing radiologists' prior image reference heuristics that are heuristic
      oriented and data intensive. We detailed the system architecture and design of
      the knowledge-based patient image pre-fetching system. Our architecture design is
      based on a client-mediator-server framework, capable of coping with a dynamic
      environment characterized by distributed, heterogeneous, and highly autonomous
      data source systems. To adapt to changes in radiologists' patient prior image
      reference heuristics, ID3-based multidecision-tree induction and CN2-based
      multidecision induction learning techniques were developed and evaluated.
      Experimentally, we examined effects of the pre-fetching system we created on
      radiologists' examination readings. Preliminary results show that the knowledge
      based patient image pre-fetching system more accurately supports radiologists'
      patient prior image reference needs than the current practice adopted at the
      study site and that radiologists may become more efficient, consultatively
      effective, and better satisfied when supported by the pre-fetching system than
      when relying on the study site's pre-fetching practice.

PMID- 11300216
TI  - A computer-aided diagnosis system for digital mammograms based on fuzzy-neural
      and feature extraction techniques.
AB  - An intelligent computer-aided diagnosis system can be very helpful for
      radiologist in detecting and diagnosing microcalcifications' patterns earlier and
      faster than typical screening programs. In this paper, we present a system based
      on fuzzy-neural and feature extraction techniques for detecting and diagnosing
      microcalcifications' patterns in digital mammograms. We have investigated and
      analyzed a number of feature extraction techniques and found that a combination
      of three features, such as entropy, standard deviation, and number of pixels, is
      the best combination to distinguish a benign microcalcification pattern from one
      that is malignant. A fuzzy technique in conjunction with three features was used
      to detect a microcalcification pattern and a neural network to classify it into
      benign/malignant. The system was developed on a Windows platform. It is an easy
      to use intelligent system that gives the user options to diagnose, detect,
      enlarge, zoom, and measure distances of areas in digital mammograms.

PMID- 11300217
TI  - A new concept toward computer-aided medical diagnosis--a prototype implementation
      addressing pulmonary diseases.
AB  - The original concept that led to the structuring of a computer-based medical
      decision support system (DSS) that is able to support a physician's diagnosis is
      introduced in this paper. The concept's implementation modeled a generic DSS, the
      core of which are an integrated knowledge/information base (KIB) along with the
      inference properties of a data evaluator. The KIB encapsulates the necessary
      medical knowledge and experience in the form of rules and constraints, preemptive
      tasks, and actual patients' clinical data. The data evaluator handles approved
      medical subjective and objective criteria for assessing the KIB's data. The data
      evaluator incorporates a medical standard data gathering and decision process,
      structured upon the principles of the clinical differential diagnosis methodology
      and has been integrated in the system by means of both algorithmic and artificial
      intelligence techniques. The novel model and the resulted computer-based package
      have been extensively tested under the Pulmonary Department, University Regional
      Hospital Patras, Patras, Greece.

PMID- 11300218
TI  - Simultaneous estimation of physiological parameters and the input function--in
      vivo PET data.
AB  - Dynamic imaging with positron emission tomography (PET) is widely used for the in
      vivo measurement of regional cerebral metabolic rate for glucose (rCMRGlc) with
      [18F]fluorodeoxy-D-glucose (FDG) and is used for the clinical evaluation of
      neurological disease. However, in addition to the acquisition of dynamic images,
      continuous arterial blood sampling is the conventional method to obtain the
      tracer time-activity curve in blood (or plasma) for the numeric estimation of
      rCMRGlc in mg glucose/100-g tissue/min. The insertion of arterial lines and the
      subsequent collection and processing of multiple blood samples are impractical
      for clinical PET studies because it is invasive, has the remote, but real
      potential for producing limb ischemia, and it exposes personnel to additional
      radiation and risks associated with handling blood. In this paper, based on our
      previously proposed method for extracting kinetic parameters from dynamic PET
      images, we developed a modified version (post-estimation method) to improve the
      numerical identifiability of the parameter estimates when we deal with data
      obtained from clinical studies. We applied both methods to dynamic neurologic FDG
      PET studies in three adults. We found that the input function and parameter
      estimates obtained with our noninvasive methods agreed well with those estimated
      from the gold standard method of arterial blood sampling and that rCMRGlc
      estimates were highly correlated (r = 0.973). More importantly, no significant
      difference was found between rCMRGlc estimated by our methods and the gold
      standard method (P > 0.16). We suggest that our proposed noninvasive methods may
      offer an advance over existing methods.

PMID- 11300219
TI  - Optimal scheduling of tracing computations for real-time vascular landmark
      extraction from retinal fundus images.
AB  - Recently, this group published fast algorithms for automatic tracing
      (vectorization) of the vasculature in live retinal angiograms, and for the
      extraction of visual landmarks formed by vascular bifurcations and crossings.
      These landmarks are used for feature-based image matching for controlling a
      computer-assisted laser retinal surgery instrument currently under development.
      This paper describes methods to schedule the vascular tracing computations to
      maximize the rate of growth of quality of the partial tracing results within a
      frame cycle. There are two main advantages. First, progressive image matching
      from partially extracted landmark sets can be faster, and provide an earlier
      indication of matching failure. Second, the likelihood of successful image
      matching is greatly improved since the extracted landmarks are of the highest
      quality for the given computational budget. The scheduling method is based on
      quantitative measures for the computational work and the quality of landmarks. A
      coarse grid-based analysis of the image is used to generate seed points for the
      tracing computations, along with estimates of local edge strengths, orientations,
      and vessel thickness. These estimates are used to define criteria for real-time
      preemptive scheduling of the tracing computations. It is shown that the optimal
      schedule can only be achieved in perfect hindsight, and is thus unrealizable.
      This leads to scheduling heuristics that approximate the behavior of the optimal
      algorithm. One such approximation produced approximately 400% improvement in the
      quality of the partial results at a defined milestone, as compared to random
      scheduling. The resulting algorithm can be readily implemented on conventional
      and multiple-processor systems, and is being applied to computer-assisted laser
      retinal surgery.

PMID- 11300220
TI  - Atherogenic lipoprotein profile in families with and without history of early
      myocardial infarction.
AB  - In this study we compared several parameters characterizing differences in the
      lipoprotein profile between members of families with a positive or negative
      family history of coronary artery disease (CAD). In addition to regular
      parameters such as the body mass index (BMI), total plasma cholesterol (TC), low
      density (LDL-C) and high density (HDL-C) cholesterol and triglycerides (TG) we
      estimated the fractional esterification rate of cholesterol in apoB lipoprotein
      depleted plasma (FER(HDL)) which reflects HDL and LDL particle size distribution.
      A prevalence of smaller particles for the atherogenic profile of plasma
      lipoproteins is typical. Log (TG/HDL-C) as a newly established atherogenic index
      of plasma (AIP) was calculated and correlated with other parameters. The cohort
      in the study consisted of 29 young (< 54 years old) male survivors of myocardial
      infarction (MI), their spouses and at least one offspring (MI group; n=116). The
      control group consisted of 29 apparently healthy men with no family history of
      premature CAD in three generations, their spouses and at least one offspring
      (control group; n=124). MI families had significantly higher BMI than the
      controls, with the exception of spouses. Plasma TC did not significantly differ
      between MI and the controls. MI spouses had significantly higher TG. Higher LDL-C
      had MI survivors only, while lower HDL-C had both MI survivors and their spouses
      compared to the controls. FER(HDL) was significantly higher in all the MI
      subgroups (probands 25.85+/-1.22, spouses 21.55+/-2.05, their daughters 16.93+/
      1.18 and sons 19.05+/-1.33 %/h) compared to their respective controls (men
      20.80+/-1.52, spouses 14.70+/-0.98, daughters 13.23+/-0.74, sons 15.7+/-0.76 %/h,
      p<0.01 to p<0.05). Log(TG/HDL-C) ranged from negative values in control subjects
      to positive values in MI probands. High correlation between FER(HDL) and Log
      (TG/HDL-C) (r=0.80, p<0.0001) confirmed close interactions among TG, HDL-C and
      cholesterol esterification rate. The finding of significantly higher values of
      FER(HDL) and Log (TG/HDL-C) indicate higher incidence of atherogenic lipoprotein
      phenotype in members of MI families. The possibility that, in addition to genetic
      factors, a shared environment likely contributes to the familial aggregation of
      CAD risk factors is supported by a significant correlation of the FER(HDL) values
      within spousal pairs (control pairs: r=0.51 p<0.01, MI pairs: r=0.41 p<0.05).

PMID- 11300221
TI  - Activities of superoxide dismutase and catalase in erythrocytes and plasma
      transaminases of goldfish (Carassius auratus gibelio Bloch.) exposed to cadmium.
AB  - Four groups of goldfish were exposed to cadmium in a concentration of 20 mg Cd/l
      water under aquarium conditions. The duration of exposure was 1, 4, 7 and 15
      days. It was shown that the activity of superoxide dismutase (SOD) in the red
      blood cells (RBC) significantly decreased after the first day of cadmium
      exposure. However, the SOD activity increased after 7 and 15 days of cadmium
      treatment. Elevated activity of catalase (CAT) was found in erythrocytes of
      cadmium-treated fishes after 15 days, whereas plasma GOT levels was increased
      after 7 and 15 days and GPT levels after 1, 4, 7 and 15 days of cadmium
      treatment. This was accompanied by a significant decrease of blood hemoglobin
      concentrations (after 15 days) and hematocrit values (after 7 and 15 days).
      However, the concentration of blood glucose significantly increased after 1, 4, 7
      and 15 days of cadmium exposure. These results indicate that cadmium causes
      oxidative stress and tissue damage in the exposed fishes.

PMID- 11300222
TI  - Satellite nucleoli in the megakaryocytic lineage of rats.
AB  - The present study was undertaken to provide more information on the incidence of
      satellite nucleoli in developmental stages of the megakaryocytic lineage.
      Satellite nucleoli representing solitary silver stained nucleolus organizer
      regions (AgNORs) present in nuclei in addition to other nucleolar types were
      observed in all stages of megakaryocytic development. However, the incidence of
      satellite nucleoli was more frequent in mature megakaryocytes than in less
      differentiated immature megakaryoblasts and naked megakaryocytic nuclei
      representing the terminal stages of megakaryocytic development after loss of the
      cytoplasm transformed to thrombocytes. There is a possibility that the increased
      incidence of satellite nucleoli in mature megakaryocytes might be due to the loss
      of AgNORs from active nucleoli characteristic for immature cells. The decreased
      incidence of satellite nucleoli in naked megakaryocytic nuclei might reflect
      their disintegration in the terminal stages of the megakaryocytic development.

PMID- 11300223
TI  - Effect of starvation on branched-chain alpha-keto acid dehydrogenase activity in
      rat heart and skeletal muscle.
AB  - The aim of the present study was to investigate changes in the activity of
      branched-chain alpha-keto acid dehydrogenase (BCKAD) in skeletal muscle and the
      heart during brief and prolonged starvation. Fed control rats and rats starved
      for 2, 4 and 6 days were anesthetized with pentobarbital sodium before heart and
      hindlimb muscles were frozen in situ by liquid nitrogen. Basal (an estimate of in
      vivo activity) and total (an estimate of enzyme amount) BCKAD activities were
      determined by measuring the release of 14CO2 from alpha-keto[1-(14)C]isocaproate.
      The activity state of BCKAD complex was calculated as basal activity in
      percentages of total activity. Both basal and total activities and the activity
      state of the BCKAD were lower in skeletal muscles than in the heart. In both
      tissues, starvation for 2 or 4 days caused a decrease in the basal activity and
      activity state of BCKAD. On the contrary, in the heart and muscles of animals
      starved for 6 days a marked increase in basal activity and activity state of
      BCKAD was observed. The total BCKAD activity was increasing gradually during
      starvation both in muscles and the heart. The increase was significant in muscles
      on the 4th and 6th day of starvation. The demonstrated changes in BCKAD activity
      indicate significant alterations in branched-chain amino acid (BCAA) and protein
      metabolism during starvation. The decreased BCKAD activity in skeletal muscle and
      heart observed on the 2nd and 4th day of starvation prevents the loss of
      essential BCAA and is an important factor involved in protein sparing. The
      increased activity of BCKAD on the 6th day of starvation indicates activated
      oxidation of BCAA and accelerated protein breakdown.

PMID- 11300224
TI  - Metabolism of branched-chain amino acids in starved rats: the role of hepatic
      tissue.
AB  - Parameters of branched-chain amino acids (BCAA; leucine, isoleucine and valine)
      and protein metabolism were evaluated using L-[1-(14)C]leucine and alpha-keto[1
      (14)C]isocaproate (KIC) in the whole body and in isolated perfused liver (IPL) of
      rats fed ad libitum or starved for 3 days. Starvation caused a significant
      increase in plasma BCAA levels and a decrease in leucine appearance from
      proteolysis, leucine incorporation into body proteins, leucine oxidation, leucine
      oxidized fraction, and leucine clearance. Protein synthesis decreased
      significantly in skeletal muscle and the liver. There were no significant
      differences in leucine and KIC oxidation by IPL. In starved animals, a
      significant increase in net release of BCAA and tyrosine by IPL was observed,
      while the effect on other amino acids was non-significant. We conclude that the
      protein-sparing phase of uncomplicated starvation is associated with decreased
      whole-body proteolysis, protein synthesis, branched-chain amino acid (BCAA)
      oxidation, and BCAA clearance. The increase in plasma BCAA levels in starved
      animals results in part from decreased BCAA catabolism, particularly in heart and
      skeletal muscles, and from a net release of BCAA by the hepatic tissue.

PMID- 11300225
TI  - Different expression of renin-angiotensin system components in hearts of
      normotensive and hypertensive rats.
AB  - Tissue renin-angiotensin systems are known to behave differently from the
      circulating renin-angiotensin system (RAS). It has already been proposed that not
      only the circulating RAS, but also RAS localized in the cardiac tissue plays an
      important role in the heart failure. The objective of this study was to compare
      the gene expression of individual components of the renin-angiotensin system in
      hearts of normotensive and hypertensive rats. Two genetically hypertensive rat
      strains--spontaneously hypertensive rats (SHR) and hereditary
      hypertriglyceridemic rats (HTG)--were compared with Wistar-Kyoto (WKY) and Lewis
      (LEW) normotensive controls. In addition, developmental changes in gene
      expression of individual components of cardiac RAS were studied in 20-day-old
      fetuses, 2-day-old newborns and 3-month-old HTG and LEW rats. In our study, the
      angiotensinogen gene expression did not differ either among adult normotensive
      and hypertensive strains, or during development. In contrast, the renin gene
      expression was significantly increased in hearts of hypertensive compared to
      normotensive rats. Moreover, a 5-fold increase of renin mRNA was observed in
      hearts of HTG rats between day 2 and the third month of age. There was also an
      age-dependent increase of ACE gene expression in both HTG and LEW rats which was
      substantially delayed in HTG hearts. In conclusion, the results of our study
      suggest that overexpression of the cardiac renin gene in hypertensive strains
      could participate in the structural and functional changes of the heart during
      the development of hypertension.

PMID- 11300226
TI  - The association study of DRD2, ACE and AGT gene polymorphisms and metamphetamine
      dependence.
AB  - We investigated the association between metamphetamine dependence and TaqI A
      polymorphism of the dopamine receptor D2 gene (DRD2), I/D polymorphism in
      angiotensin-converting enzyme (ACE) and M235T polymorphism of the angiotensinogen
      gene (AGT) in 93 unrelated metamphetamine-dependent subjects and 131 controls.
      Our results did not prove any association of TaqI A polymorphism of the DRD2
      gene, I/D polymorphism of ACE gene, and M235T polymorphism of AGT gene with the
      metamphetamine dependence in Caucasians of Czech origin. However, a significant
      difference in allele I frequency between male and female control groups for the
      I/D ACE polymorphism (p<0.03) was found.

PMID- 11300227
TI  - Twenty-Four hour blood pressure profile in subjects with different subtypes of
      primary aldosteronism.
AB  - The aim of our study was to evaluate the potential differences in blood pressure
      (BP) profile in subjects with different forms of primary aldosteronism (PA).
      Simultaneously, we studied the effects of PA treatment on BP curve. We therefore
      monitored 24-hour ambulatory blood pressure values in 22 subjects with
      aldosterone-producing adenoma (APA), 22 subjects with idiopathic
      hyperaldosteronism (IHA) and 33 subjects with essential hypertension (EH) as
      controls. We found a significantly attenuated nighttime systolic BP decline in
      the APA group (P=0.02). Patients with IHA had lower nighttime systolic BP values
      (P=0.01) and also a diastolic BP decline (P=0.02) during the night in comparison
      with EH. We did not detect any significant differences in BP profile
      characteristics between APA and IHA. Specific treatment of primary aldosteronism
      (adrenalectomy, treatment with spironolactone) led to the normalization of the BP
      curve with a marked BP decline. Our study thus demonstrates a blunted diurnal BP
      variability in patients with primary aldosteronism the specific treatment of
      which normalized previously attenuated nocturnal BP fall.

PMID- 11300228
TI  - Short-term dynamics of relative coordination between respiratory movements, heart
      rate and arterial pressure fluctuations within the respiratory frequency range.
AB  - The possible linear short-term coordination between respiratory movements (RESP),
      heart rate fluctuations (HRF), and arterial blood pressure fluctuations (BPF) in
      conscious human beings has not yet been investigated because of the restricted
      time resolution of conventional time series analysis. At present, this short-term
      dynamics as an expression of relative coordination can be quantified by newly
      developed adaptive autoregressive modeling of time series using Kalman filtering.
      Thus, in 6 conscious healthy volunteers, RESP, HRF, and BPF were recorded during
      10 min in the supine position, at rest and during paced breathing. A considerable
      part of calculated ordinary and partial coherence sequences of short-term
      resolution between RESP and HRF, RESP and BPF, and partially between HRF and BPF
      showed patterns varying in time that could be correlated to changes between
      gradual coordinations (coherence changing between 0.40 and 0.95). They were more
      seldom complete or absent. There were mostly opposite changes between partial
      coherence sequences RESP-HRF/BPF and RESP-BPF/HRF demonstrating competitive
      behavior between these coordinations. Paced breathing did not essentially affect
      any observed characteristics. Therefore, these coherence dynamics are not
      essentially dependent on voluntary breathing movements. We conclude that to a
      different extent these linear and changing couplings between RESP, HRF, and BPF
      in conscious human beings exhibit properties of short-term complete and more
      frequently gradual coordinations showing dynamics that can not be determined by
      conventional methods.

PMID- 11300229
TI  - Cardiovascular and hormonal changes with different angles of head-up tilt in men.
AB  - The purpose of this study was to assess the endocrine status, thoracic impedance,
      blood concentration, and hemodynamic dose-responses using different angles of
      passive head-up tilt (HUT) ranging from 12 degrees to 70 degrees in the same
      subjects. Measurements were performed during 20 min supine position (pre-HUT), 30
      min upright (HUT12, HUT30, HUT53, or HUT70), and 20 min supine (post-HUT);
      subjects 70 min in the supine position only (HUT0) served as resting controls.
      Norepinephrine increased above resting control values by 19, 44, 80, and 102%;
      epinephrine by 30, 41, 64, and 68%; aldosterone by 29, 62, 139, and 165%; plasma
      renin activity n. s., 41, 91, and 89%; vasopressin n.s., 27, 47, and 59%;
      thoracic bioimpedance n. s., 8, 13, and 16%; heart rate n. s., 5, 26, and 45%,
      and mean arterial pressure n. s., 5, 7, and 10%; at min 27 of HUT12, HUT30,
      HUT53, and HUT70, respectively. Pulse pressure decreased with HUT53 and HUT70 by
      4 and 10%. Hematocrit increased by 0.2, 1.7, 6.3, and 7.2%, respectively. Blood
      density increased by 2.3 and 3.0 g/l, plasma density by 1.7 and 1.8 g/l with
      HUT53 and HUT70. After finishing HUT, heart rate fell to values which stayed
      below pre-HUT, and also below resting control levels for > or = 5 min ("post
      orthostatic bradycardia") even after the lowest orthostatic load (HUT12).
      Thoracic impedance and arterial pressure remained increased after terminating
      HUT30, HUT53, and HUT70. In conclusion, passive orthostatic loading of different
      extent produces specific dose-responses of different magnitude in the endocrine
      system, blood composition, thoracic impedance, and hemodynamic variables. The
      heart rate is depressed even after HUT12, while arterial blood pressure and
      thoracic impedance exceed pre-stimulus levels after greater head-up tilt,
      indicating altered cardiovascular response after passive orthostasis.

PMID- 11300230
TI  - Permanent depression of plasma cGMP during long-term space flight.
AB  - The purpose of this study was to investigate plasma concentrations of cyclic
      guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP) during and
      after real and simulated space flight. Venous blood was obtained 3 min after the
      beginning and 2 min after the lower body negative pressure maneuver in two
      cosmonauts preflight (supine), inflight, and postflight (supine) and in five
      other subjects before, at the end, and 4 days after a 5-day head-down tilt (-6
      degrees) bed rest. In cosmonaut 1 (10 days in space), plasma cGMP fell from
      preflight 4.3 to 1.4 nM on flight day 6, and was 3.0 nM on the fourth day after
      landing. In cosmonaut 2 (438 days in space), it fell from preflight 4.9 to 0.5 nM
      on on flight day 3, and stayed <0.1 nM with 5, 9, and 14 months in space, as well
      as on the fourth day after landing. Three months after the flight his plasma cGMP
      was back to normal (6.3 nM). Cosmonaut 2 also displayed relatively low inflight
      ANP values but returned to preflight level immediately after landing. In a ground
      based simulation on five other persons, supine plasma cGMP was reduced by an
      average of 30% within 5 days of 6 degrees head-down tilt bed rest. The data
      consistently demonstrate lowered plasma cGMP with real and simulated
      weightlessness, and a complete disappearance of cGMP from plasma during, and
      shortly after long-duration space flight.

PMID- 11300231
TI  - Effects of transdermal application of 7-oxo-DHEA on the levels of steroid
      hormones, gonadotropins and lipids in healthy men.
AB  - The aim of this study was to investigate the effect of 7-oxo-DHEA
      (dehydroepiandrosterone) on the serum levels of steroid sexual hormones,
      gonadotropins, lipids and lipoproteins in men. 7-oxo-DHEA was applied onto the
      skin as a gel to 10 volunteers aged 27 to 72 years for 5 consecutive days. The
      single dose contained 25 mg 7-oxo-DHEA. Serum concentrations of testosterone,
      estradiol, cortisol, androstenedione, luteinizing hormone (LH), follicle
      stimulating hormone (FSH), sex hormone binding globulin (SHBG), total
      cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoprotein A-I and B
      and lipoprotein(a) were measured before the beginning and shortly after the end
      of the steroid application. After the treatment, we noted the following
      significant changes: a decline of testosterone and estradiol levels, increase of
      LH, HDL-cholesterol and apolipoprotein A-I levels. The decrease of total
      cholesterol levels was of the borderline significance. A slight but significant
      increase was found in apolipoprotein B and lipoprotein(a). The most expressive
      was the fall of the atherogenic index. We suggest that the gel containing 7-oxo
      DHEA might be a suitable drug for improving the composition of the steroid and
      lipid parameters in elderly men.

PMID- 11300232
TI  - Biphasic ventilatory response to hypoxia in unanesthetized rats.
AB  - To determine the role of postinspiratory inspiratory activity of the diaphragm in
      the biphasic ventilatory response to hypoxia in unanesthetized rats, we examined
      diaphragmatic activity at its peak (DI), at the end of expiration (DE), and
      ventilation in adult unanesthetized rats during poikilocapnic hypoxia (10 % O2)
      sustained for 20 min. Hypoxia induced an initial increase in ventilation followed
      by a consistent decline. Tidal volume (VT), frequency of breathing (fR), DI and
      DE at first increased, then VT and DE decreased, while fR and DI remained
      enhanced. Phasic activation of the diaphragm (DI-DE) increased significantly at
      10, 15 and 20 min of hypoxia. These results indicate that 1) the ventilatory
      response of unanesthetized rats to sustained hypoxia has a typical biphasic
      character and 2) the increased end-expiratory activity of the diaphragm limits
      its phasic inspiratory activation, but this increase cannot explain the secondary
      decline in tidal volume and ventilation.

PMID- 11300233
TI  - Effects of estradiol benzoate and progesterone on superoxide dismutase activity
      in the thymus of rats.
AB  - The activity of mitochondrial superoxide dismutase (MnSOD) and cytosol superoxide
      dismutase (CuZnSOD) was measured in corresponding subcellular fractions prepared
      from the thymi of intact and chronically gonadectomized (GX) rats of both sexes,
      as well as of GX male and female rats injected subcutaneously with a single dose
      of 5 microg estradiol benzoate (EB) and/or 2 mg progesterone (P). Animals were
      sacrificed 2 h or 24 h following hormone treatment. In the females, the activity
      of MnSOD in the thymus was stable during the estrous cycle and did not change
      after ovariectomy. Treatment of GX females with estradiol benzoate resulted 2 h
      later in a significant elevation of MnSOD activity, whereas 24 h later the
      activity returned back to control values. On the other hand, treatment of GX
      females with progesterone had no effect on the MnSOD activity. However, combined
      hormone treatment, in which EB injection preceded progesterone injection by one
      hour, enhanced the effect on MnSOD activity similar to that of estradiol benzoate
      alone. The activity of CuZnSOD in cycling rats was increased in proestrus,
      whereas removal of the ovaries kept the values at low diestrus and estrus levels.
      Contrary to MnSOD, CuZnSOD activity did not change after EB treatment of GX
      females, while progesterone increased the enzyme activity at 2 h and 24 h after
      hormone treatment. However, combined EB+P treatment proved to be ineffective. In
      the males, neither MnSOD nor CuZnSOD activity was affected by the removal of
      testes or by progesterone treatment of GX animals. Only EB injection to GX rats
      significantly increased CuZnSOD activity 24 h later.

PMID- 11300234
TI  - Insulin action after resistive training in insulin resistant older men and women.
AB  - OBJECTIVES: To determine the effects of resistive training (RT) on insulin action
      and assess the determinants of the changes in insulin action. DESIGN:
      Longitudinal study. SETTING: Outpatient setting. PARTICIPANTS: Eighteen older men
      and older postmenopausal women (65-74 years) with normal (6 men and 5 women) or
      impaired glucose tolerance (4 men and 3 women). INTERVENTION: Six months of
      progressive whole-body RT. MEASUREMENTS: Upper and lower body strength was
      assessed by the one repetition maximum test. Total body fat and fat-free mass
      (FFM) were determined by dual-energy x-ray absorptiometry before and after 6
      months of RT. Insulin sensitivity was estimated from the relationship of glucose
      utilization (M) to the concentration of insulin (I) during the last 30 minutes of
      3-hour hyperinsulinemic-euglycenic clamps (240 pmol x min(-2) x min(-1)) (M/I)
      before and after RT. RESULTS: RT significantly improved upper- and lower-body
      muscular strength (P < .005). FFM increased after RT in the entire group (P <
      .01) with no significant change in body fat. Although the change in M was larger
      in men (13%) than women (3%), the difference was not significant. The change in M
      was a function of initial M (r = -0.53, P < .05). There was a trend (0.060+/
      0.006 vs 0.066+/-0.006 micromol x kg(-1) x min(-1)/pmol/l, n = 18) for M/I to
      increase after RT in the combined group of men and women (P = .06). There were no
      significant relationships between changes in M or M/I with changes in body
      composition or strength. CONCLUSION: A 6-month RT program tends to improve
      insulin action in insulin-resistant older adults. These results suggest that RT
      may be useful in ameliorating insulin resistance that often occurs with physical
      inactivity, obesity, and loss of muscular strength in older insulin resistant men
      and women.

PMID- 11300235
TI  - Factors associated with healthy aging: the cardiovascular health study.
AB  - OBJECTIVES: To identify factors associated with remaining healthy in older
      adults. DESIGN: Longitudinal cohort study. SETTING: Data were collected at the
      four Cardiovascular Health Study field centers. PARTICIPANTS: 5,888 participants
      age 65 years and older in the Cardiovascular Health Study. MEASUREMENTS: Presence
      of chronic disease was assessed at baseline and over a maximum 7-year follow-up
      period. Participants who were free of chronic disease (no cardiovascular disease
      (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except
      nonmelanoma skin cancer) at the baseline examination were then monitored for the
      onset of incident cancer, cardiovascular disease, and fatal outcomes. RESULTS: A
      high proportion of these older adults was healthy at the initial examination and
      remained healthy over the follow-up period. Numerous behavioral factors were
      associated with continued health, including physical activity, refraining from
      cigarette smoking, wine consumption (women), higher educational status, and lower
      waist circumference. A number of CVD risk factors and subclinical disease
      measures were associated with continued health, including higher high-density
      lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal
      nmedial thickness, lower blood pressure, lower C-reactive protein, and higher
      ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not
      smoking, and not taking aspirin remained significant predictors of health even
      after controlling for CVD risk factors and subclinical disease in older adults.
      CONCLUSIONS: These data suggest that a number of modifiable behavioral factors
      (physical activity, smoking, and obesity) and cardiovascular risk factors
      (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance
      of good health in older adults.

PMID- 11300236
TI  - Vascular risk and cognitive impairment in an older, British, African-Caribbean
      population.
AB  - OBJECTIVES: In an older, British, African-Caribbean population with high
      prevalence rates of hypertension and diabetes mellitus, we ascertained clinical
      vascular disease (stroke or ischemic heart disease) and vascular risk (including
      hypertension, diabetes, and lipid profile) and investigated their associations
      with cognitive impairment. DESIGN: Cross-sectional community-based study.
      SETTING: The sample was drawn from registration lists for seven primary care
      services in south London, United Kingdom. PARTICIPANTS: 278 individuals, age 55
      to 75, who were born in a Caribbean nation. MEASUREMENTS: Participants were
      interviewed and examined for cardiovascular risk factors, including a blood test
      for lipid profile and fibrinogen. A battery of 11 psychometric tests was
      administered blind to medical status. Cognitive impairment was defined on the
      basis of a composite measure derived from individual test scores. RESULTS:
      Seventy-nine (28%) subjects were classified as having relative cognitive
      impairment and were compared with the remainder of the sample. Marked differences
      were seen between low and normal/high educational levels in the strength of
      associations between measures of vascular risk and cognitive impairment.
      Hypertension, diabetes, and raised triglycerides were significant factors in
      those with lower levels of education. Low fibrinogen (negatively associated),
      high cholesterol, and manual occupation were significant factors in those with
      normal/high levels of education. Physical exercise was negatively associated with
      cognitive impairment: an association that persisted after adjustment for age,
      occupation, depression, and physical disability and after excluding subjects with
      the most severe imipairment. CONCLUSION: Measures of vascular risk were
      associated with relative cognitive impairment in this population. These
      associations were modified by previous educational attainment. Physical activity
      was negatively associated with cognitive impairment.

PMID- 11300237
TI  - Colonization of skilled-care facility residents with antimicrobial-resistant
      pathogens.
AB  - OBJECTIVES: To determine the frequency of and risk factors for colonization of
      skilled-care unit residents by several antimicrobial-resistant bacterial species,
      methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
      enterococcus (VRE), or extended-spectrum-beta-lactamase-producing (ESBL
      producing) (ceftazidime resistant) Klebsiella pneumoniae or Escherichia coli.
      DESIGN: Point-prevalence survey and medical record review. SETTING: The skilled
      care units in one healthcare facility. PARTICIPANTS: 120 skilled-care unit
      residents. MEASUREMENTS: Colonization by each of the four antimicrobial-resistant
      pathogens during a point-prevalence survey, using rectal, nasal, gastrostomy-tube
      site, wound, and axillary cultures, June 1-3, 1998; 117 (98%) had at least one
      swab collected and 114 (95%) had a rectal swab collected. Demographic and
      clinical characteristics were evaluated as risk factors for colonization. All
      isolates were strain typed by pulsed-field gel electrophoresis of total genomic
      deoxyribonucleic acid. RESULTS: Of 117 participants, 50 (43%) were culture
      positive for > or =1 antimicrobial-resistant pathogen: MRSA (24%), ESBL-producing
      K. pneumoniae (18%) or E. coli (15%), and VRE (3.5%). Of 50 residents culture
      positive for any of these four antimicrobial-resistant species, 13 (26%) were
      colonized by more than one resistant species; only three (6%) were on contact
      isolation precautions at the time of the prevalence survey. Risk factors for
      colonization varied by pathogen: total dependence on healthcare workers (HCWs)
      for activities of daily living (ADLs) and antimicrobial receipt for MRSA, total
      dependence on HCWs for ADLs for ESBL-producing K. pneumoniae, and antimicrobial
      receipt for VRE. No significant risk factors were identified for colonization by
      ESBL-producing E. coli. Among colonized patients, there was a limited number of
      strain types for MRSA (24 patients, 4 strain types) and ESBL-producing K.
      pneumoniae (21 patients, 3 strain types), and a high proportion of unique strain
      types for VRE (4 patients, 4 strain types) and FSBL-producing E. coli (17
      patients, 10 strain types). CONCLUSION: A large unrecognized reservoir of skilled
      care-unit residents was colonized by antimicrobial-resistant pathogens, and co
      colonization by more than one target species was common. To prevent transmission
      of antimicrobial-resistant pathogens in long-term care facilities in which
      residents have high rates of colonization, infection-control strategies may need
      to be modified. Potential modifications include enhanced infection-control
      strategies, such as universal gloving for all or high-risk residents, or
      screening of high-risk residents, such as those with total dependence on HCWs for
      ADLs or recent antimicrobial receipt, and initiation of contact-isolation
      precautions for colonized residents.

PMID- 11300238
TI  - The appropriateness of drug use in an older nondemented and demented population.
AB  - OBJECTIVE: To assess the extent of inappropriateness of drug use in an older
      nondemented and demented population. DESIGN: Descriptive analysis based on data
      from a sample of older subjects age 81 years and older. Data were collected from
      the second follow-up conducted in 1994-1996. SETTING: A population-based study of
      the Kungsholmen project in Stockholm, Sweden. PARTICIPANTS: Drug information was
      obtained from 681 subjects with a mean age of 86.9 years. The subjects were
      predominantly women (78%). Thirteen percent resided in institutions and 27.6%
      were diagnosed with dementia. MEASUREMENTS: Dementia diagnosis based on DSM III
      R. Criteria for inappropriateness of drug use: use of drugs with potent
      anticholinergic properties, drug duplication, potential drug-drug and drug
      disease interactions, and inappropriate drug dosage. RESULTS: The mean number of
      drugs used was 4.6: 4.5 drugs for nondemented and 4.8 for demented subjects.
      Nondemented subjects more commonly used cardiovascular-system drugs and demented
      subjects used nervous-system drugs. Demented subjects were more commonly exposed
      to drug duplication and to drugs with potent anticholinergic properties, both
      involving the use of psychotropic drugs. Nondemented subjects were more commonly
      exposed to potential drug-disease interactions, mostly with the use of
      cardiovascular drugs. The most common drug combination leading to a potential
      interaction was the use of digoxin with furosemide, occurring more frequently
      among nondemented subjects. The most common drug-disease interaction was the use
      of beta-blockers and calcium antagonists in subjects with congestive heart
      failure. The doses of drugs taken by both nondemented and demented subjects were
      mostly lower than the defined daily dose. CONCLUSION: There was substantial
      exposure to presumptive inappropriateness of drug use in this very old
      nondemented and demented population. The exposure of demented subjects to
      psychotropic drugs and nondemented subjects to cardiovascular drugs reflect the
      high frequency of prescribing these drugs in this population.

PMID- 11300239
TI  - Illness representations according to age and effects on health behaviors
      following coronary artery bypass graft surgery.
AB  - OBJECTIVES: To determine if illness representations differ as a function of age
      and how these representations, in conjunction with age, predict postoperative
      health behaviors. DESIGN: Prospective study of patients undergoing coronary
      artery bypass graft (CABG) surgery. SETTING: A large metropolitan hospital
      providing regional cardiac care for patients in a tri-state area, located in
      Pittsburgh, Pennsylvania. PARTICIPANTS: All consenting patients (N = 309) from a
      consecutive series of patients scheduled for CABG surgery between January 1992
      and January 1994. To be eligible for participation, patients could not be
      scheduled for any other coincidental surgery (e.g., valve replacement), and could
      not be in cardiac intensive care or experiencing angina at the time of the
      referral. Participants were predominantly male (70%) and married (80%), and
      averaged 62.8 years of age. MEASUREMENTS: Postoperative self-reported health
      behaviors. RESULTS: Older participants awaiting CABG surgery were significantly
      more likely to believe old age to be the cause of their coronary heart disease
      (CHD) and significantly less likely to believe genetics, health-damaging
      behaviors, health-protective behaviors, and emotions to be the cause of their CHD
      than were younger participants awaiting surgery. Furthermore, the older
      participants were significantly more likely to believe they had no control over
      the disease and that the disease would be gone after surgery, and reported fewer
      postoperative health behavior changes than did younger participants. CONCLUSION:
      These findings demonstrate significant differences in illness representations as
      a function of age. Furthermore, differences in postoperative health behaviors
      were consistent with differing illness representations.

PMID- 11300240
TI  - Depressive disorder as a predictor of physical disability in old age.
AB  - OBJECTIVES: To determine whether the occurrence of depression predicts physical
      disability in older people. DESIGN: A longitudinal epidemiological study with a
      follow-up of 5 years. SETTING: A comparison between depressed and nondepressed
      participants. PARTICIPANTS: The series consisted of the persons who participated
      in the longitudinal epidemiological study on depression in old age performed in
      Ahtari, Finland. The first round of interviews and examinations was performed in
      1984/1985 and the second round in 1989/1990. The study series (N = 786) was
      composed of persons functionally independent in activities of daily living (ADLs)
      during the first round and alive and participating in both rounds. MEASUREMENTS:
      Depression was determined according to DSM-III criteria. Physical functional
      abilities were measured with self-assessments of ability to manage ADLs. RESULTS:
      In bivariate analyses, depression at the baseline did not predict lowering of
      functional abilities during follow-up, but the occurrence of depression with a
      long-term or relapsing course during follow-up and the onset of depression during
      follow-up in persons not depressed at the baseline predicted lowering of
      functional abilities during follow-up. The logistic regression analyses showed
      the presence of the following variables measured during the first round--older
      age, low basic education, poor self-perceived health, and occurrence of a
      physical disease--and the onset of the following diseases during follow-up--any
      physical disease, neurological disease, cerebrovascular disease, or depressive
      symptoms (in persons nondepressed at the baseline)--predicted lowered functional
      abilities after a follow-up of 5 years. CONCLUSION: Depression that developed
      during the follow-up in previously nondepressed persons was associated with an
      increased risk for lowering of functional abilities, even when controlling for
      age, sociodemographic factors, physical diseases, and baseline disabilities.
      Depressed older people are at high risk for physical disability, and an
      individually planned program to maintain their functional abilities by training
      in ADLs and instrumental activities of daily living (IADLs) and physical exercise
      should be included in their treatment.

PMID- 11300241
TI  - Racial differences in the cost of treating men with early-stage prostate cancer.
AB  - OBJECTIVE: To compare the cost and resource utilization in the evaluation,
      treatment, and 6-month follow-up of African-American and White men undergoing
      either external beam radiation therapy (XRT) or radical prostatectomy (RP) for
      early-stage prostate cancer. DESIGN: Retrospective analysis of cost and resource
      utilization data from encrypted patient-specific hospital inpatient, hospital
      outpatient, and physician/supplier data files. SETTING: National Medicare claims
      data from 1993 through 1996. PARTICIPANTS: A random 5% national sample of
      Medicare beneficiaries from the Health Care Financing Administration Public Use
      Files for 1993 through 1996. MEASUREMENTS: Inpatient, outpatient, and
      physician/supplier Medicare costs. RESULTS: African-American men undergoing RP
      for early-stage prostate cancer had significantly higher costs ($21,878 vs
      $18,786, P < .0001) than did White men. Most of the difference occurred in the
      inpatient setting. African-American men undergoing XRT had significantly greater
      costs ($18,131 vs $15,734, P < .0001) than did White men. Most of this difference
      was generated by longer duration of XRT treatments. CONCLUSIONS: In early-stage
      prostate cancer, charges for RP and XRT in African-American men are higher when
      compared with those for White men.

PMID- 11300242
TI  - Outbreak of campylobacteriosis at a senior center.
AB  - OBJECTIVES: In August 1997, campylobacteriosis was diagnosed in four older
      persons in one Connecticut town. We investigated this outbreak to determine its
      cause and to identify appropriate preventive measures. We also analyzed
      surveillance data to assess the impact of campylobacteriosis among persons age 65
      years and older in Connecticut. DESIGN: The outbreak was investigated through a
      case-control study and an environmental investigation. Surveillance data were
      from population-based, active foodborne disease surveillance. SETTING: The
      outbreak and environmental studies were conducted at a senior center identified
      as the one eating place common to all four patients. Active surveillance data
      were from three Connecticut counties during 1996/1997. PARTICIPANTS: We
      administered a questionnaire to senior center attendees. A case was defined as
      onset of diarrhea with fever or abdominal cramps during August 20-25 in a person
      who ate at the senior center during August 18-20. Respondents without illness
      meeting the case definition who ate at the senior center during August 18-20 were
      controls. MEASUREMENTS: Case-control study participants were asked about symptoms
      of gastrointestinal illness and meals and foods eaten at the center. The
      environmental investigation gathered information about food preparation
      procedures and facilities. Active surveillance data were analyzed to determine
      age-specific annual campylobacteriosis incidence rates and proportions of cases
      involving hospitalization. RESULTS: For the case-control study, there were 66
      respondents (16 case patients, 50 controls), representing approximately 52% of
      August 18-20 attendees. Case patients were more likely than controls to have
      eaten at a Hawaiian luau at the center. The most strongly implicated food was
      sweet potatoes. Review of food preparation procedures identified multiple
      opportunities for cross-contamination from raw meats to other foods. In
      Connecticut's active surveillance area during 1996/1997, the annual
      campylobacteriosis incidence rate was highest among young adults, but the
      proportion of hospitalized cases was highest among persons age 70 years and
      older. CONCLUSION: Campylobacter transmission occurred at the luau, likely
      because of cross-contamination in the kitchen. This investigation emphasizes the
      importance of strict separation of raw meats from other foods during preparation.
      Careful attention to these measures is particularly important when an older
      population is served.

PMID- 11300243
TI  - Predicting stroke recovery: three- and six-month rates of patient-centered
      functional outcomes based on the orpington prognostic scale.
AB  - OBJECTIVE: To provide recovery rates after stroke for specific functions using
      the Orpington Prognostic Scale (OPS). DESIGN: Prospective cohort. SETTING:
      Hospital and community. PARTICIPANTS: 413 stroke survivors entered the study 3 to
      14 days after suffering a stroke. MEASUREMENTS: A cohort of hospitalized stroke
      survivors were recruited 3 to 14 days after stroke and assessed at 1, 3, and 6
      months poststroke for neurological, functional, and health status. Baseline OPS
      score was used to predict five functional outcomes at 3 and 6 months using
      development and validation datasets and receiver operating characteristic (ROC)
      curves. RESULTS: In 413 stroke survivors, functional recovery rates at 3 and 6
      months were similar. Baseline OPS predicted significant differences in recovery
      rates for all five outcomes (P < .0001 for all five outcomes at 3 and 6 months).
      Personal care dependence was present at 3 months in only 3% of persons with
      baseline OPS scores of 3.2 or less compared with over 50% with OPS of 4.8 or
      higher. Independent personal care, meal preparation, and self-administration of
      medication were achieved by 80% who had baseline OPS scores of 2.4 or lower
      compared with less than 20% when OPS scores were 4.4 or higher. Independent
      community mobility was achieved in 50% of those who had OPS scores of 2.4 or
      lower but only 3% of those with OPS scores of 4.4 or higher. The area under ROC
      curves assessing OPS scores against each of the five outcomes ranged from 0.805
      to 0.863 at 3 months and 0.74 to 0.806 at 6 months. CONCLUSION: OPS scores can
      predict widely differing rates of functional recovery in five important
      functional abilities. These estimates can be useful to survivors, families,
      providers, and healthcare systems who need to plan for the future.

PMID- 11300244
TI  - A decision aid for long-term tube feeding in cognitively impaired older persons.
AB  - OBJECTIVE: To describe the development and evaluation of a decision aid for long
      term tube feeding in cognitively impaired older people. DESIGN: Before-and-after
      study. SETTING: Acute care hospitals in Ottawa, Canada. PARTICIPANTS: Substitute
      decision makers for 15 cognitively impaired inpatients 65 years and older being
      considered for placement of a percutaneous endoscopic gastrostomy tube.
      MEASUREMENTS: Questionnaires were used to compare the substitute decision makers'
      knowledge, decisional conflict, and predisposition regarding feeding tube
      placement before and after exposure to the decision aid. The acceptability of the
      decision aid was also assessed. RESULTS: Substitute decision makers significantly
      increased their knowledge (P = .004) and decreased their decisional conflict (P =
      .004) regarding long-term tube feeding after using the decision aid. The impact
      of the decision aid on predisposition toward the intervention was greatest for
      those who were unsure of their preferences at baseline. All substitute decision
      makers found the decision aid helpful and acceptable despite very difficult and
      emotional circumstances. CONCLUSIONS: A decision aid improves the decision-making
      process for long-term tube feeding in cognitively impaired older patients by
      decreasing decisional conflict and by promoting decisions that are informed and
      consistent with personal values. There are particular challenges for developing
      and evaluating these tools in the context of end-of-life decisions.

PMID- 11300245
TI  - Low vision in the geriatric population: rehabilitation and management.
AB  - Older persons represent the fastest growing segment of individuals with visual
      impairments in industrialized countries. This population is expected to grow
      dramatically in the coming years. This article discusses the common age-related
      changes in vision and the most prevalent visual impairments associated with
      aging, and the resulting functional implications. It includes information for
      health care professionals about preparing an older person to benefit from low
      vision rehabilitation services, environmental evaluations and modifications, and
      orientation to the environment. The importance of functional assessment and
      instruction in the use of visual skills and vision devices is stressed. The
      article also emphasizes the need for teamwork to provide a full scope of
      rehabilitation services to older adults with low vision, and the importance of
      support by family members and caregivers to maximize coping, adjustment,
      independence and quality of life.

PMID- 11300246
TI  - Effect of beta blockers on mortality and morbidity in persons treated for
      congestive heart failure.

PMID- 11300247
TI  - In re HMO versus fee-for-service systems.

PMID- 11300248
TI  - In re alcohol use in older adults.

PMID- 11300249
TI  - Patients with urinary incontinence and falls.

PMID- 11300250
TI  - Aneurysm of the left ventricle: a two-decade silent history.

PMID- 11300251
TI  - Contribution of glutathione S-transferase M1 to longevity.

PMID- 11300252
TI  - In re Megestrol acetate treatment.

PMID- 11300253
TI  - Testosterone use for rehabilitation of older men.

PMID- 11300254
TI  - Pain management in nursing homes.

PMID- 11300255
TI  - The hypothesis of age-associated neovasculopathy with recurrent bleeding.

PMID- 11300256
TI  - What is an author?

PMID- 11300257
TI  - The incidence of facial nerve dehiscence at surgery for cholesteatoma.
AB  - OBJECTIVE: Facial paralysis can occur after surgery for cholesteatoma. The risk
      of facial nerve injury is great when the nerve is not covered by its normal bony
      Fallopian canal. The objective of this study was to identify the incidence of
      facial nerve dehiscence in patients undergoing surgery for cholesteatoma. STUDY
      DESIGN: Retrospective chart review. SETTING: Tertiary referral hospital. PATIENT
      POPULATION: An assessment of all cases performed by the senior author from 1991
      to 1999 revealed 59 patients with adequate data available for analysis. These
      patients ranged in age from 3 to 92 years. In all, 67 surgical procedures.
      INTERVENTION: Surgery for cholesteatoma, including tympanoplasty and
      mastoidectomy. MAIN OUTCOME MEASURE: The presence of facial nerve bony dehiscence
      after exenteration of disease, and postoperative facial nerve function. RESULTS:
      In 33% of the total procedures analyzed, 30% of the initial procedures, and 35%
      of the revision procedures, the patients were found to have facial nerve bony
      dehiscence. The dehiscence was present in the tympanic portion of the facial
      nerve in the vast majority of patients. Of the 97% of patients with normal
      preoperative facial nerve function, all retained normal function postoperatively.
      CONCLUSIONS: Facial nerve dehiscence in our series was far greater than that
      reported in the literature, underscoring the fact that this is an under
      appreciated condition. These findings suggest that surgeons should be highly
      vigilant when dissecting near the facial nerve. Intraoperative facial nerve
      monitoring has been shown to be of value in facial nerve preservation during
      acoustic neuroma resections, and may have a role during surgery for
      cholesteatoma.

PMID- 11300258
TI  - Hyperectasis: the hyperinflated tympanic membrane: the middle ear as an actively
      controlled system.
AB  - OBJECTIVE: To describe and analyze a middle ear condition in which the steady
      state of the middle ear pressure is elevated above the atmospheric pressure.
      SETTING AND STUDY DESIGN: This is a long-term survey of 59 patients from a
      private clinic who were observed on routine examination to have a ballooned out
      (hyperinflated) tympanic membrane. INTERVENTION: All patients underwent hearing
      tests, tympanometry, and Shullers (lateral) mastoid radiography. MAIN OUTCOME
      MEASURES: A hyperinflated tympanic membrane indicates a middle ear pressure that
      is higher than atmospheric pressure. The ballooned tympanic membrane returns to
      its physiological level after being punctured. This pressure situation is the
      reverse or opposite of atelectasis and is therefore termed hyperectasis.
      Hyperectasis, like atelectasis, is associated with a poorly pneumatized mastoid.
      RESULTS: Fifty-nine hyperectatic ears persisted in their hyperinflated state for
      weeks, months, or even years. The hyperectasis was preceded by atelectasis, and
      both conditions occasionally changed one into the other. The ballooned part of
      the tympanic membrane is usually thin and "scarred." Hyperectasis is not a rare
      situation and, once recognized, can be readily encountered in an otologic clinic.
      CONCLUSIONS: Like most biologic systems (e.g., blood pressure, temperature), the
      middle ear's central feature, i.e., pressure, also has a dynamic character
      vacillating up and down. It is conceivable that middle ear pressure is also
      actively regulated and controlled with the aid of a feedback mechanism. Passage
      of gas through the eustachian tube or absorption by diffusion-perfusion is also
      at least partly an active process. The up and down middle ear pressure
      vacillations are usually clinically benign and do not lead to any pathologic
      features as long as they are buffered by an accompanying normal mastoid
      pneumatization. It is the ear with a nonpneumatized mastoid that has limited
      ability to buffer pressure changes and that will present as an atelectasis, a
      retraction pocket, or (eventually a cholesteatoma) or their reverse, a
      hyperectatic tympanic membrane.

PMID- 11300259
TI  - Hearing results of ossiculoplasty in Austin-Kartush group A patients.
AB  - OBJECTIVE: To compare hearing results in patients who underwent ossiculoplasty
      for Austin-Kartush group A impairments (incus erosion, malleus handle present,
      stapes superstructure present) with the results in patients with an intact
      ossicular chain who required only myringoplasty. The literature on hearing
      results of ossiculoplasty with different types of prostheses and different
      techniques is reviewed. PATIENTS AND STUDY DESIGN: This study retrospectively
      reviews a series of 181 consecutive ossiculoplasties and 204 consecutive
      myringoplasties. SETTING: The study was carried out partly at a private practice
      and partly in an academic tertiary referral center. MAIN OUTCOME MEASURES: This
      study complies with levels 1 and 2 of the guidelines recommended by the American
      Academy of Otolaryngology--Head and Neck Surgery (1995). RESULTS: When success
      was defined as a postoperative air-bone gap within 10 dB, the success rate was
      higher for myringoplasty (81%) than for ossiculoplasty (55%). When success was
      defined as a postoperative air-bone gap within 20 dB, the success rate was 97% in
      myringoplasties and 85% in ossiculoplasties. There was no significant
      deterioration over time of the mean postoperative air-bone gap for any frequency.
      CONCLUSION: Cumulative data from several authors show that -50% of patients
      undergoing partial ossiculoplasty have a postoperative air-bone gap of 0 to 10
      dB, and 80% have a postoperative air-bone gap of 0 to 20 dB. Equally good results
      may be achieved with autograft (no difference was found between interposition of
      the incus or the head of the malleus), homograft, or alloplastic partial
      prostheses. With alloplastic total prostheses, 36% of patients have a
      postoperative air-bone gap of 0 to 10 dB, and 74% have a postoperative air-bone
      gap of 0 to 20 dB.

PMID- 11300260
TI  - Current use of implants in middle ear surgery.
AB  - OBJECTIVE: The authors report the results of a survey of members of the American
      Otological Society (AOS) and the American Neurotology Society (ANS) regarding
      their use of prostheses currently available for ossiculoplasty and stapedectomy.
      These findings are compared with a similar study presented by one of the authors
      in 1989. METHODS: Questionnaires were sent to the entire membership of the AOS
      and ANS with questions regarding biomaterial and prosthesis usage for stapes and
      chronic ear surgery, as well as satisfaction with each type of prosthesis used.
      Of the 575 questionnaires mailed, 274 (47%) were returned. Only 248 of the
      respondents performed middle ear surgery (43%), and their responses constitute
      the database for this study. RESULTS: For those respondents performing stapes
      surgery in both 1989 and 1999, the mean number of cases per year has increased
      from 32 to 37 (p < or = 0.004). The mean number of chronic ear cases has also
      increased from 95 in 1989 to 110 in 1999 (p < or = 0.001). As a biomaterial,
      hydroxyapatite prostheses are used by most surgeons (82%), followed by autograft
      and homograft bone (72%), autograft and homograft cartilage (62%), and Plastipore
      (59%). (Although 62% of respondents use cartilage, only 4.4% ranked it first in
      preference.) In 1989, bone was used most (93%), followed by cartilage (78%) and
      Plastipore (81%). Hydroxyapatite, which had just been introduced as a
      biomaterial, was used by only 9% of respondents. For stapes prostheses in 1999,
      the majority of respondents used stainless steel/platinum (71%), bucket handle
      (69%), or partial fluoroplastic (56%) prostheses. There was a high overall
      satisfaction rate in the use of most of these prostheses (> 85%), with several
      exceptions. The lowest satisfaction rate was 71% for Plastipore partial ossicular
      replacement prosthesis and total ossicular replacement prosthesis. Usage and
      satisfaction rates are presented for specific types of implants and compared with
      the earlier survey findings. CONCLUSION: The current use of implants in middle
      ear surgery demonstrates a specific pattern with a high degree of user
      satisfaction. The preference for implants by respondents has remained stable over
      the past 10 years; there has been a decrease in the percentage of use of bone,
      cartilage, and Plastipore with a corresponding increase in the use of
      hydroxyapatite.

PMID- 11300261
TI  - Recent outcome of tympanoplasty in the elderly.
AB  - OBJECTIVE: To investigate the outcome of tympanoplasty in the elderly (patients
      older than 60 years) compared with younger patients. PATIENTS AND STUDY DESIGN:
      Retrospective review of 87 (28.3%) older patients among a total of 307 patients
      with chronic otitis media with or without cholesteatoma who were surgically
      treated at a university hospital by the senior author. Follow-up was
      systematically provided at the same institution. INTERVENTIONS: Surgery included
      tympanoplasty with mastoidectomy performed as the primary procedure in 358 ears.
      Tympanoplasty was performed with canal-wall-up or canal-wall-down with canal wall
      reconstruction, ossiculoplasty with autologous or homologous ossicle
      interposition or columella. Mean follow-up was 30 months (range, 12-70 months).
      MAIN OUTCOME MEASURES: Pre- and postoperative air- and bone-conduction thresholds
      were calculated as an average of three speech frequencies (0.5, 1, and 2 kHz).
      Analysis was subsequently carried out on the postoperative air-bone gap, hearing
      gain, and postoperative problems such as elevation of the bone-conduction
      threshold, delayed epithelialization, and reperforation of the eardrum.
      Statistical analysis was performed by chi-square or Student's t-test. A p value
      less than 0.05 was considered significant. RESULTS: Compared with results from
      younger patients, there was no particular disadvantage in postoperative hearing
      results and complications in the elderly, although preoperative bone-conduction
      thresholds were gradually worsened with age. CONCLUSIONS: There is no
      contraindication for tympanoplasty in older patients if their physical status is
      the same or better than what is normal for their chronological age.

PMID- 11300262
TI  - Middle ear prosthesis displacement in high-strength magnetic fields.
AB  - HYPOTHESIS: Middle ear prostheses made from nonmagnetic, magnetic resonance (MR)
      compatible metals reportedly displace ex vivo in the presence of high magnetic
      fields used in MR imaging (MRI). The authors postulate that the prosthesis
      displacement seen with "nonmagnetic" MR-compatible prostheses ex vivo may not be
      clinically significant in vivo. METHODS: Middle ear prostheses made from
      ferromagnetic (420F stainless steel) and nonmagnetic MR-compatible metals (316L
      stainless steel and platinum) were examined for magnetic field interactions at
      4.7 Tesla (T). Ex vivo testing consisted of measurements of the translational and
      rotational motion of the prosthesis induced by the static magnetic field. In vivo
      testing was assessed by implanting prostheses in cadaveric temporal bones and
      performing clinical MRI sequences. Prosthesis displacement was measured
      semiquantitatively. RESULTS: Angular deflection was observed in all samples made
      from nonmagnetic stainless steel. The negative control (platinum) demonstrated no
      deflection, and the positive controls (ferromagnetic stainless steel) deflected
      >90 degrees. Torque analysis showed movement in five of five nonmagnetic
      stainless steel prostheses. Prostheses made from nonmagnetic stainless steel
      remained in place without appreciable loosening in vivo after MRI. Prostheses
      made with known ferromagnetic properties were displaced at 4.7 T but not at 1.5
      T. CONCLUSION: Middle ear prostheses made from low-magnetic stainless steel do
      move in the presence of high magnetic fields ex vivo; however, this does not
      appear to be clinically or statistically significant in vivo at 4.7 T. Magnetic
      resonance imaging should be undertaken with caution in individuals with
      prostheses made from stainless steel with strong ferromagnetic properties.

PMID- 11300263
TI  - Histopathology of residual and recurrent conductive hearing loss after
      stapedectomy.
AB  - HYPOTHESIS: Histopathologic examination of temporal bones from patients who had
      undergone stapedectomy may provide information concerning the causes of both
      residual and recurrent conductive hearing loss (CHL). BACKGROUND: Although
      closure of the air-bone gap to within 10 dB occurs in approximately 90% of
      primary stapedectomies, a residual CHL occurs in approximately 10% and recurrent
      CHL may occur in up to 35% of cases. Putative causes of failure of surgery as
      determined during revision include erosion of the incus, bony regrowth at the
      oval window, and displacement of the prosthesis. Most reports on the
      histopathologic findings of temporal bones from such patients have focused on
      complications of surgery, with little attempt to correlate postoperative air-bone
      gap with the observed histopathology. METHODS: A retrospective review of the
      author's collection of temporal bones ascertained 22 cases with postoperative CHL
      of 10 dB or greater (air-bone gap averaged at 500, 1,000, 2,000, 3,000, and 4,000
      Hz, using postoperative air- and bone-conduction levels) after stapedectomy.
      These temporal bones were prepared by standard methodology for light microscopy.
      RESULTS: Of the 22 cases with postoperative CHL equal to or greater than 10 dB,
      there were 19 with residual CHL, 2 with recurrent CHL, and 1 with both residual
      and recurrent CHL. The most common histopathologic correlates of residual and
      recurrent hearing loss included resorptive osteitis of the incus (64%);
      obliteration of the round window by otosclerosis (23%); the prosthesis lying on a
      residual footplate fragment (23%); the prosthesis abutting the bony margin of the
      oval window (18%); adhesions in the middle ear (14%); and new bone formation in
      the oval window (14%). CONCLUSIONS: Histopathologic examination of temporal bones
      from patients who in life had undergone stapedectomy provides useful information
      concerning causes of both residual and recurrent CHL. These data provide a basis
      for improving both surgical technique and prosthesis design.

PMID- 11300264
TI  - Cerebro-oculo-facio-skeletal syndrome as a human example for accelerated cochlear
      nerve degeneration.
AB  - BACKGROUND: Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare autosomal
      recessive disorder that includes microcephaly, severe mental retardation, and
      multiple congenital anomalies. Otologic findings are usually limited to
      descriptions of the auricles. PATIENT AND METHODS: The authors report inner ear
      histopathologic findings of a deceased 13-year-old patient with COFS. A
      histologic study of the inner ear in COFS syndrome has not yet been described.
      This patient was documented as having a profound bilateral sensorineural hearing
      loss at the age of 2 years. RESULTS: Histologic evaluation revealed accelerated
      neural and neuronal degeneration at the cochlear and retrocochlear levels.
      Remaining myelinated nerve fibers, counted in the spiral lamina, had degenerated
      by up to 97% when compared with normal innervation densities. Afferent nerve
      fibers innervating inner hair cells were completely absent, whereas medial
      efferent fibers to outer hair cells were found. Vestibular nerve fibers were less
      affected. CONCLUSION: The authors report inner ear findings that differ from
      animal models of primary cochlear neural degeneration and that resemble the
      pattern of hereditary cochlear nerve degeneration reported in Friedreich's
      ataxia.

PMID- 11300266
TI  - Reliability of manometric eustachian tube function tests in children.
AB  - OBJECTIVE: To assess the reliability of manometric eustachian tube function tests
      in children with ventilation tubes in situ. STUDY DESIGN: Repeated manometric
      eustachian tube function tests during one session. SETTING: The study took place
      at a secondary referral hospital and a tertiary referral hospital. PATIENTS:
      Ninety-nine children with ventilation tubes in situ because of persistent otitis
      media with effusion. MAIN OUTCOME MEASURES: Opening pressure (Po), closing
      pressure (Pc), and tubal function group. RESULTS: Analysis of Po and Pc showed a
      decrease with repeated measurement (p = 0.0001 and p = 0.001, respectively). The
      effect of repeated measurement on Po was more pronounced than the effect on Pc.
      The results of the first and second pressure equilibration tests showed 99%
      agreement. CONCLUSIONS: This study showed good reproducibility of the categorized
      results of the pressure equilibration test, whereas the results of the forced
      response test seemed to be less reproducible and showed a downward shift with
      repeated measurement. A single measurement using wet swallowing and starting
      pressures of 100 and -100 daPa and the mean of the first three measurements of
      the Po and Pc are sufficient to determine tubal function. Further studies are
      needed to determine the discriminative power of these tests in children with
      different degrees of middle ear disease.

PMID- 11300265
TI  - Computer-aided virtual surgery for congenital aural atresia.
AB  - HYPOTHESIS: Computer-enhanced three-dimensional (3D) computed tomography (CT)
      provides accurate spatial representation of the complex surgical anatomy of
      congenitally atretic ears, and is superior to conventional CT for surgical
      planning. BACKGROUND: The surgical repair of congenital aural atresia is
      challenging. Conventional CT, routinely used for surgical planning, is limited in
      its ability to represent spatial relationships between important structures.
      Because of the lack of density differences between bony structures in the ear, 3D
      CT has thus far been useful for representing surface contour but not internal
      anatomy. METHODS: A two-level segmentation scheme was developed to distinguish
      structures in the temporal bone. 3D CT reconstructions of congenital ears were
      produced with a high-resolution helical scanner. An interactive tool was used to
      mark the ossicles and facial nerve. The segmentation scheme was used to color
      enhance the ossicles and otic capsule, and render the surrounding bone
      translucent. "Virtual surgery" was then performed by subtracting a cylindrical
      volume of bone lateral to the atresia plate. The enhanced 3D CT reconstructions
      were correlated with intraoperative video recordings. RESULTS: In four congenital
      ears, computer-enhanced 3D CT was highly predictive of the actual anatomy.
      Surgery was avoided in two anatomically unfavorable cases. CONCLUSION: Computer
      enhanced 3D CT is a major advance over conventional CT for demonstrating the
      complex spatial relationships in congenitally atretic ears.

PMID- 11300268
TI  - Comparison of pediatric Clarion recipients with and without the electrode
      positioner.
AB  - OBJECTIVE: To compare surgical experience and measures of electrode and patient
      performance of children who were implanted with the Clarion (Advanced Bionics,
      Sylmar, CA, U.S.A.) device with and without the new electrode positioner (EP).
      STUDY DESIGN: Prospectively and retrospectively collected data were compared
      between two independent groups. SETTING: Tertiary care children's hospital.
      PATIENTS: Twenty-four children (mean age, 3.0 years) implanted during the
      original Food and Drug Administration (FDA) clinical trial required for
      commercial approval of the Clarion and 15 children (mean age, 3.4 years)
      implanted with the EP as part of an ongoing FDA trial. INTERVENTION: Cochlear
      implant with and without EP. MAIN OUTCOME MEASURES: Electrical psychophysical
      threshold, most comfortable loudness level (MCL), electrode impedance, and speech
      perception measures were compared at 3 and 6 months after initial stimulation.
      RESULTS AND CONCLUSION: All children had complete insertion of electrodes. No
      difficulty inserting the EP occurred nor did subsequent related complications.
      Subjects with the EP had significantly lower threshold and MCL levels. Electrode
      impedance declined on stimulated electrodes in both groups. Meaningful Auditory
      Integration Scale scores significantly improved in both groups; the EP group
      appeared to receive as much benefit as the non-EP group.

PMID- 11300267
TI  - A vestibular phenotype for Waardenburg syndrome?
AB  - OBJECTIVE: To investigate vestibular abnormalities in subjects with Waardenburg
      syndrome. STUDY DESIGN: Retrospective record review. SETTING: Tertiary referral
      neurotology clinic. SUBJECTS: Twenty-two adult white subjects with clinical
      diagnosis of Waardenburg syndrome (10 type I and 12 type II). INTERVENTIONS:
      Evaluation for Waardenburg phenotype, history of vestibular and auditory
      symptoms, tests of vestibular and auditory function. MAIN OUTCOME MEASURES:
      Results of phenotyping, results of vestibular and auditory symptom review
      (history), results of vestibular and auditory function testing. RESULTS:
      Seventeen subjects were women, and 5 were men. Their ages ranged from 21 to 58
      years (mean, 38 years). Sixteen of the 22 subjects sought treatment for vertigo,
      dizziness, or imbalance. For subjects with vestibular symptoms, the results of
      vestibuloocular tests (calorics, vestibular autorotation, and/or pseudorandom
      rotation) were abnormal in 77%, and the results of vestibulospinal function tests
      (computerized dynamic posturography, EquiTest) were abnormal in 57%, but there
      were no specific patterns of abnormality. Six had objective sensorineural hearing
      loss. Thirteen had an elevated summating/action potential (>0.40) on
      electrocochleography. All subjects except those with severe hearing loss (n = 3)
      had normal auditory brainstem response results. CONCLUSION: Patients with
      Waardenburg syndrome may experience primarily vestibular symptoms without hearing
      loss. Electrocochleography and vestibular function tests appear to be the most
      sensitive measures of otologic abnormalities in such patients.

PMID- 11300269
TI  - Tinnitus suppression in patients with cochlear implants.
AB  - OBJECTIVE: To determine the degree of tinnitus suppression provided by currently
      available multichannel cochlear implants and to determine factors that can
      influence this process. STUDY DESIGN: Prospective cohort. SETTING: Tertiary-care
      referral center. PATIENTS: Thirty-eight adult patients (18 years of age or older)
      with severe-to-profound hearing loss and tinnitus who met criteria for cochlear
      implantation. INTERVENTION: Cochlear implantation with a multichannel cochlear
      implant device. MAIN OUTCOME MEASURES: Patients rated the intensity of their
      tinnitus using a semiquantitative scale before and after cochlear implantation.
      These data were analyzed to determine the significance of the reduction of
      tinnitus after implantation. Tinnitus levels after implantation were also
      analyzed to determine whether the level of speech recognition, patient gender, or
      the implant type influenced the degree of tinnitus reduction. RESULTS:
      Statistical analysis revealed a significant reduction in tinnitus intensity in
      patients using cochlear implants, with 35 of 38 patients (92%) experiencing a
      reduction in tinnitus intensity. All multichannel implants studied afforded
      similar degrees of tinnitus suppression. The degree of tinnitus reduction was not
      correlated with speech recognition, as measured by CID Everyday Sentence scores.
      Female patients had significantly greater degrees of tinnitus before
      implantation, but both male and female patients demonstrated similar levels of
      tinnitus after implantation. No patient experienced greater levels of tinnitus
      after implantation. CONCLUSION: All currently available multichannel cochlear
      implant devices provide effective and similar levels of tinnitus suppression when
      activated. Exacerbation of tinnitus as a result of cochlear implantation does not
      represent a significant risk. The mechanisms by which cochlear implants exert
      tinnitus suppression are, as yet, unclear.

PMID- 11300270
TI  - Mastoid oscillation in canalith repositioning for paroxysmal positional vertigo.
AB  - OBJECTIVE: The canalith repositioning procedure (CRP) was developed to treat
      paroxysmal positional vertigo (PPV). Successful CRP results in cessation of PPV
      and positional nystagmus. Mastoid oscillation (MO) has been advocated to enhance
      the efficacy of CRP. The authors sought to objectively determine the effect of MO
      on CRP. STUDY DESIGN: Retrospective review. SETTING: Ambulatory referral center.
      PATIENTS: Patients with PPV seen from 1993 through 1999 (N = 168). INTERVENTIONS:
      Canalith repositioning procedure performed without MO (n = 104) and performed
      with MO (n = 64). MAIN OUTCOME MEASURE: Presence or absence of nystagmus on Dix
      Hallpike testing 6 weeks after CRP. RESULTS: Eighty-four percent of patients
      treated with MO had resolution, and 16% had persistent nystagmus. Seventy-three
      percent of patients without MO had resolution, and 27% had persistent nystagmus.
      Although suggesting a trend, the difference did not reach the level of
      significance (p = 0.151). CONCLUSIONS: Mastoid oscillation does not significantly
      enhance the efficacy of the CRP.

PMID- 11300271
TI  - Long-term follow-up of transtympanic gentamicin for Meniere's syndrome.
AB  - OBJECTIVE: Recent studies have shown that transtympanic gentamicin for Meniere's
      syndrome is effective. Current treatment protocols vary. One concept has been to
      perform a chemical ablation; the other has been to perform a chemical alteration.
      Ablation requires multiple injections and is effective in controlling the
      vertigo, but it is associated with a significant incidence of hearing loss.
      Chemical alteration uses a minimal dose to reduce vestibular function without
      affecting cochlear function. STUDY DESIGN: Prospective. SETTING: Tertiary medical
      center. PATIENTS: Patients had classic unilateral Meniere's syndrome that was
      unresponsive to medical therapy. INTERVENTION: A single injection of gentamicin
      is given, and the patient is seen 1 month after injection. If indicated, the
      patient receives another injection and is reevaluated 1 month later. MAIN OUTCOME
      MEASURES: Control of vertigo and maintenance of hearing using the American
      Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines (1995).
      RESULTS: Fifty-six patients have documented follow-up for 2 years or more, and 21
      have 4 years or more of follow-up. This article presents the 4-year results as
      outlined by the AAO-HNS guidelines. Vertigo classes A and B were seen in 82% of
      patients. The patients followed 2 to 4 years had 86% vertigo class A and B
      results. Those followed 4 years or more show 76% with a vertigo class A or B
      result. In this study there has been minimal cochlear loss. There was vestibular
      change clinically, which was documented by electronystagmography. CONCLUSIONS: It
      appears that a single transtympanic gentamicin injection is effective in
      controlling the vertigo of Meniere's syndrome. Cochlear impact has been minimal.
      It is most useful for those patients who have failed medical management and are
      severely affected but not totally incapacitated by the disease.

PMID- 11300272
TI  - Acoustic neuroma: predominance of Antoni type B cells in tumors of patients with
      vestibular paresis.
AB  - OBJECTIVE: This study aimed to investigate whether in patients with acoustic
      neuroma (AN), the presence or absence of vestibular symptoms is related to the
      histologic characteristics of the tumor. STUDY DESIGN: The study design was a
      retrospective clinical study. SETTING: The study was conducted at a tertiary
      referral center. PATIENTS: A group of eight patients with unilateral AN and
      normal vestibular function was compared with a group of AN patients, matched for
      tumor size, with vestibular paresis. METHODS: The methods were vestibular
      examination of the patients and morphometric analysis of the histologic specimens
      of their tumors. MAIN OUTCOME MEASURES: The outcomes were measured by vestibular
      function and by the relative quantity of Antoni type A or type B cell tissue.
      RESULTS: The tumors of patients with vestibular paresis appeared to contain
      significantly more Antoni B cells and fewer Antoni A cells than did the tumors of
      patients with normal vestibular function. CONCLUSIONS: Besides morphologic
      differences, type B cells may display a distinct behavior compared with type A
      cells. Presumably, in AN patients the development of a vestibular paresis appears
      to be related to the biologic activity of type B cells in the tumor.

PMID- 11300273
TI  - Primary malignant melanoma of the cerebellopontine angle.
AB  - BACKGROUND: Malignant tumors of the cerebellopontine angle are very rare,
      accounting for less than 1% of lesions at this site. These may be primary or
      secondary tumors of the temporal bone, central nervous system (CNS), or
      leptomeninges. Malignant melanoma is uncommon, accounting for 1.5% of all types
      of malignant tumors. Metastatic melanoma is a frequent cause of CNS metastasis,
      often with leptomeningeal spread. Primary leptomeningeal melanoma is, however,
      rare and even more so at the cerebellopontine angle. The prognosis for CNS
      malignant melanoma is generally very poor. PATIENT: The authors describe the case
      of a 29-year-old woman with unilateral hearing loss and facial paresis. Magnetic
      resonance imaging (MRI) demonstrated a mass that was thought to be an acoustic
      neuroma but was seen to involve the cochlea as well as the internal auditory
      meatus and cerebellopontine angle. The lesion was subsequently excised completely
      by a trans-labyrinthine approach, with facial nerve preservation, and was shown
      on histologic examination to be a malignant melanoma. Further comprehensive
      investigation did not reveal a primary extracranial site or any sign of CNS
      spread. The clinical features of this case, including the radiologic and
      histologic findings, are described, and literature concerning management is
      reviewed.

PMID- 11300274
TI  - Enlarged middle fossa vestibular schwannoma surgery: experience with 735 cases.
AB  - OBJECTIVE: To show the clinical outcome in patients with sporadic vestibular
      schwannoma (VS) operated on by the enlarged middle cranial fossa approach (EMFA).
      STUDY DESIGN: Retrospective case review. SETTING: A tertiary referral center with
      four neurotologists experienced in EMFA surgery. PATIENTS: There were 376 women
      and 359 men, with a mean age of 51.1 years (range, 12-77). INTERVENTION: Enlarged
      middle cranial fossa approach surgery. MAIN OUTCOME MEASURES: Magnetic resonance
      imaging and computed tomography scans were used for follow-up and re-evaluation
      of the operative sites. Facial nerve function and hearing were tested. RESULTS:
      Overall complete VS removal was achieved in 97.1% of patients. There were two
      recurrences (0.3%) after microscopically complete tumor removal. Depending on the
      tumor size, postoperative normal and near-normal facial outcome ranged from 83%
      to 99% (average, 92%), and hearing at or near the preoperative level (+/-15 dB
      pure-tone average or +/-15% speech discrimination) was preserved in 60.2%, 48.2%,
      23.9%, and 17.6%, respectively. CONCLUSIONS: The EMFA is an excellent low
      morbidity approach for VS removal with limited cerebellopontine angle extension
      (2 cm). Specific advantages of the EMFA are the superior internal auditory canal
      exposure, resulting in an extremely low tumor recurrence rate; best capability
      for hearing preservation; and minimal incidence of cerebrospinal fluid leaks.
      Postoperative facial function outcome compares with that of other surgical
      approaches. The best results are achieved in subjects with small tumors and good
      hearing, advocating early diagnosis and treatment.

PMID- 11300275
TI  - Long-term control of surgically treated glomus tympanicum tumors.
AB  - OBJECTIVE: The glomus tumor is an enigmatic middle ear neoplasm commonly delayed
      in diagnosis. Frequently grouped with its skull base counterpart, surgery and
      radiation are often recommended as therapy. The objective of this report is to
      highlight the diagnosis and surgical treatment of this neoplasm in a large
      series. Tumor control in the long term is defined. STUDY DESIGN: Retrospective
      case review. SETTING: Private practice-tertiary referral center. PATIENTS: All
      patients surgically treated for glomus tympanicum tumors from May 25, 1972 to
      July 3, 1998 (N = 80). INTERVENTIONS: Surgical excision of glomus tympanicum
      tumors. MAIN OUTCOME MEASURE: Total tumor control in the long term. RESULTS:
      Surgical treatment resulted in long-term tumor control for the vast majority of
      the patients studied. CONCLUSIONS: Surgery provides excellent control of glomus
      tympanicum tumors. It is safe and well tolerated, with minimal morbidity.

PMID- 11300276
TI  - Effect of chemical sympathectomy with 6-hydroxydopamine on osteoclast activity in
      the gerbilline middle ear bulla.
AB  - HYPOTHESIS: Chemical sympathectomy with 6-hydroxydopamine (HDA) increases middle
      ear bulla bone resorption in the Mongolian gerbil. BACKGROUND: Many diseases of
      the middle ear have pathologic processes linked to abnormal bone remodeling.
      Numerous factors controlling bone remodeling have been identified. An
      understanding of these factors and their role in pathologic remodeling is
      therefore essential. Sympathectomy, induced both surgically and pharmaceutically,
      is known to increase middle ear bone resorption, suggesting a role for the
      central nervous system in bone metabolism. This effect, however, may be
      confounded by hemodynamic changes induced by hemicranial surgical sympathectomy
      or by uncertainty in the action of pharmaceutical agents on the sympathetic
      nervous system. In this experiment, a third modality with unique properties,
      chemical sympathectomy with HDA, was used to quantify further the effect of
      sympathectomy on middle ear bone remodeling. METHODS: Eight gerbils designated
      experimental received intraperitoneal injections of HDA (75 mg/kg) for 1 week,
      whereas eight animals designated control received similar injections of saline.
      One week after injections, the animals were euthanized and bulla bone samples
      were analyzed histomorphometrically to determine osteoclastic activity. In
      addition, to assess for any direct effects on bone metabolism, the activity of
      HDA was determined in vitro using the calvarial calcium release assay. RESULTS:
      The in vitro study found HDA to have no direct stimulatory activity on calcium
      release. The in vivo study showed HDA to increase osteoclastic activity
      significantly in middle ear bone. CONCLUSION: HDA-induced sympathectomy increases
      bone resorption in gerbilline middle ear bone.

PMID- 11300277
TI  - Local vestibular blood flow and systemic vascular responses to natural vestibular
      stimulation in the Mongolian gerbil.
AB  - HYPOTHESIS: Natural stimulation of the vestibular end organs will produce
      alterations in the local vestibular microvascular blood flow. BACKGROUND: The
      vestibular and cardiovascular systems require a coordinated interaction to
      maintain organ perfusion during rapid positional and postural changes. However,
      the detailed relationship of these systems is not well understood. There have
      been no previous descriptions of local vestibular blood flow (VBF) during natural
      stimulation (NS) conditions. METHODS: In vivo VBF and systemic blood pressure
      (BP) in the Mongolian gerbil during natural stimulation. Using laser Doppler
      flowmetry, the authors obtained continuous measures of local VBF in both
      anesthetized and alert gerbils during sinusoidal rotational stimuli. Simultaneous
      recordings of systemic BP were collected from the contralateral common carotid
      artery. RESULTS: The anesthetized gerbils showed stable VBF and BP during all
      vestibular stimuli. By contrast, alert subjects demonstrated a significant
      response to natural stimulation. The VBF increased 28% over baseline, and
      systemic BP increased 8% during a 45-second, 0.133-Hz sinusoid. Decreases in BP
      of 8% and 5%, respectively, were seen with a 0.10 and 0.20 Hz, 360-second
      stimulus. A corresponding determination of VBF during the extended stimulus
      conditions was not technically possible. CONCLUSIONS: To the authors' knowledge,
      these are the first in vivo descriptions of vestibular blood flow during natural
      stimulation. In the alert animals, VBF increased in response to NS. This increase
      in flow does not appear to be directly dependent on systemic blood pressure
      changes and indicates that the vestibular microvasculature is closely regulated.

PMID- 11300278
TI  - Pathophysiology of otosclerosis.
AB  - OBJECTIVE: To review current knowledge of the pathophysiology of otosclerosis and
      to review hypotheses for the amelioration of this disease. DATA SOURCES: Review
      of the literature and experimental observations by the authors. CONCLUSIONS:
      Otosclerosis is a localized disease of bone remodeling within the otic capsule of
      the human temporal bone. Unlike other similar bone diseases, it does not occur
      outside of the temporal bone. These lesions seem to begin by resorption of stable
      otic capsule bone in adults, followed by a reparative phase with bone deposition.
      There are clearly genetic factors that lead to this disease, but measles virus
      infection and autoimmunity also may play contributing roles. Surgical correction
      of the conductive hearing loss is highly effective, but nonsurgical intervention
      has not yet been shown to prevent or slow the disease. Of the factors that may
      inhibit this process, fluorides, cytokine inhibitors, and bisphosphonates, third
      generation bisphosphonates appear to hold the most promise.

PMID- 11300279
TI  - The origin of eponyms used in cochlear anatomy.
AB  - The anatomy of the cochlea, one of the most complicated parts of the inner ear,
      is associated with numerous eponyms, mostly originating from German anatomists of
      the 19th century. In addition to the organ of Corti and Reissner's membrane,
      which are the best known, nine other eponymic anatomic terms are associated with
      the cochlea: Deiters' cells, Hensen's cells, Hensen's strip, Claudius' cells,
      Boettscher's cells, Rosenthal's canal, Hardesty's membrane, Huschke's teeth, and
      Nuel's space. All of these anatomic eponyms are described, with their original
      references.

PMID- 11300280
TI  - Acquired external auditory canal occlusion.

PMID- 11300281
TI  - Aminoglycoside ototoxicity.

PMID- 11300283
TI  - Volunteerism: a new focus.

PMID- 11300282
TI  - Surgery for malleus and incus fixation.

PMID- 11300284
TI  - Intraosseous lipoma of the calcaneus.

PMID- 11300285
TI  - Bracing after revision THA: essential, expedient, and economical.

PMID- 11300286
TI  - Bracing after revision THA: unnecessary, expensive, and cruel.

PMID- 11300287
TI  - Laparoscopic transperitoneal anterior lumbar interbody fusion with cylindrical
      threaded cortical allograft bone dowels.

PMID- 11300288
TI  - Postoperative pain control in total joint arthroplasty: a prospective, randomized
      study of a fixed-dose, around-the-clock, oral regimen.
AB  - This randomized, prospective study assessed postoperative pain control in 119
      patients undergoing total joint arthroplasty. Group 1 (59 patients) received
      scheduled, around-the-clock, oral opioids and group 2 (60 patients) received oral
      opioids on an as-needed basis. Both groups had parenteral opioids available for
      breakthrough pain. The average scores for group 1 were lower than group 2.
      Differences were significant in sensory scores (AM day 1; AM and PM day 2),
      affective scores (PM day 2), total pain (PM day 2), visual analog scale (PM day
      2), and present pain intensity index (AM day 1; PM day 2). Group 1 averaged 2.05
      breakthrough pain doses and group 2 averaged 3.47 doses (P=.003), an average
      savings of 17.2% of the cost of pain medications during the first 2 postoperative
      days. The results indicate that scheduled, around-the-clock, oral opioids are an
      effective treatment regimen for postoperative pain control in total joint
      arthroplasty patients.

PMID- 11300289
TI  - Osteosynthesis and allogeneic bone grafting in complex osteoporotic fractures.
AB  - Thirty patients with osteoporotic fractures were treated operatively. An
      allogeneic bone transplant was used in combination with a conventional
      osteosynthesis in each patient. The bone graft was pulverized in a bone mill and
      used as a substitute graft to fill the bone defect, add stability, and enhance
      bone union. Fractures healed without complications in 20 patients. The
      osteosynthesis failed in 4 patients. The fracture failed to unite in an
      additional 3 patients. One deep infection occurred. A biopsy taken from the
      allogeneic bone at plate removal after fracture union demonstrated mature bone
      and new bone formation. The use of pulverized allograft bone for large bone
      defects in patients with osteoporotic fractures yields acceptable results with no
      adverse effects.

PMID- 11300290
TI  - Evaluation of intermittent pneumatic compression devices.
AB  - Venous blood flow rate in the lower extremity after applying different pneumatic
      compression devices was evaluated. Five healthy individuals, aged 21-35, were
      recruited for this study. The ability of six different pneumatic compression
      devices to increase femoral venous blood flow velocity was analyzed and compared
      to that of active and passive foot dorsiflexion. Baseline venous blood flow
      velocity was measured using an ATL Duplex Doppler before leg compression. Venous
      blood flow velocity was then monitored before, during, and after each compression
      cycle. Average peak venous velocity increased >200% on dorsiflexion of the ankle.
      Among the investigated devices, the increase in venous velocity varied
      significantly. Design of compression chambers enabling compression on the lateral
      and medial aspects of the calf produced an increase in venous velocity closest to
      active foot dorsiflexion. Foot compression devices produced the smallest increase
      in venous velocity. The relative effectiveness of pneumatic compression devices,
      particularly with respect to increasing venous blood flow in the lower extremity,
      may correlate well with how closely the device simulates the physiologic
      contraction of the calf muscles. Clinical trials are needed to further compare
      the effectiveness of these devices, as other less readily measured factors play a
      role in thromboprophylaxis.

PMID- 11300291
TI  - Effect of rotation on frontal plane deformity in idiopathic scoliosis.
AB  - To analyze the effect of rotation on frontal plane deformity in idiopathic
      scoliosis, 44 patients with idiopathic scoliosis aged 11 to 18 years were
      examined using standing anteroposterior and true AP radiographs. Axial rotation
      was measured by computed tomography. Patients were divided into two groups
      according to Cobb angle: patients with angles <30 degrees comprised group 1 and
      patients with angles >30 degrees comprised group 2. Cobb angle increased with
      true-AP projection a mean of 21.2% in group 1 and 16.7% in group 2. Rotation
      degree was significantly correlated with increasing degree of frontal plane
      deformity (P<.01) in group 1 but not in group 2 (P>.05). These results
      demonstrate the influence of rotation over frontal plane deformity and is more
      apparent at curves >30 degrees.

PMID- 11300292
TI  - Osteonecrosis in protease inhibitor-treated patients.
AB  - The introduction of protease inhibitors has proven a watershed in human
      immunodeficiency virus infection therapy and has initiated an era of highly
      active antiretroviral therapy. However, the numerous data on the effectiveness of
      these therapeutic regimens have been cited with an ever-growing number of
      communications concerning adverse reactions. In particular, the widescale use of
      protease inhibitors has underlined a series of events not evidenced in the
      controlled clinical studies that permitted the registration of these drugs. We
      are conducting a cohort multicenter study to evaluate the incidence of adverse
      events during treatment with protease inhibitors. To date, 4 cases of bilateral
      osteonecrosis of the femoral head have been reported out of 1073 person-years.
      While the pathogenesis of this event is unclear, it may be a long-term
      complication of protease inhibitor treatment.

PMID- 11300293
TI  - Histopathological characterization of melorheostosis.
AB  - Melorheostotic bone was examined histopathologically. In the severely affected
      areas, an abundance of osteoid and increased angiogenesis was observed. Increased
      osteoid without mineralization indicated the overproduction of bone matrix. Bone
      resorption also appeared to increase because osteoclasts were numerous in
      melorheostotic bone, thus suggesting a high rate of bone turnover. In addition,
      transforming growth factor-beta was immunolocalized in the periosteal
      fibroblasts, mesenchymal cells surrounding vessels, endothelial cells, and
      osteoblasts, while basic fibroblast growth factor was found in endothelial cells
      and mast cells near vessels. These cytokines may have some association with the
      exuberant bone matrix production and angiogenesis in melorheostosis.

PMID- 11300294
TI  - Lengthening of the humerus in a patient with an essential bone cyst.

PMID- 11300295
TI  - Leukemia presenting as purulent septic arthritis.

PMID- 11300296
TI  - Closed femoral shortening following Syme's amputation.

PMID- 11300297
TI  - Prophylaxis against staphylococcal infection before tertiary knee joint
      replacement.

PMID- 11300298
TI  - Solitary osteochondroma of the lower cervical spine.

PMID- 11300299
TI  - Knee dislocations.

PMID- 11300300
TI  - It's time to "think different" about the art and science of midwifery.

PMID- 11300301
TI  - Serving women in need: nurse-midwifery practice in the United States.
AB  - OBJECTIVE: Nurse-midwifery practices in the United States were examined to study
      the relationship between certified nurse-midwives' (CNMs) demographic, work
      setting, and practice characteristics in terms of clientele, practice size, and
      practice type. Factors that might influence the ability of CNMs to serve
      populations at risk for poor outcomes were given particular attention.
      METHODOLOGY: A total of 2,405 responses to a 1998 mailed survey of 6,365 nurse
      midwives ever-certified by the American College of Nurse-Midwives were analyzed.
      RESULTS: Study results indicated that CNMs continue to serve a population who
      are, based on a social risk profile, disproportionately at risk for poor
      pregnancy outcomes, including women who are uninsured (16%), immigrant (27%),
      adolescent (29%), and women of color (50%). It was also found that clientele
      varied according to practice settings: CNMs working in non-hospital, nonprofit
      settings served a clientele that was 65% nonwhite, 44% immigrant, 40% adolescent,
      and 29% uninsured; these CNMs received 61% of their client payments from
      Medicaid. CNMs working in private offices or for managed care organizations were
      less likely to serve women with these characteristics. CONCLUSION: Study results,
      taken in conjunction with research that documents the safety of nurse-midwifery
      practice, reinforce policy recommendations that support expanded access to nurse
      midwifery services. Findings also indicate a need for further research in the
      areas of CNM workload and productivity in managed care settings and the
      association between CNM race and ethnicity and the race and ethnicity of their
      clients.

PMID- 11300302
TI  - Group B streptococcal (GBS) disease screening and treatment during pregnancy:
      nurse-midwives' consistency with 1996 CDC recommendations.
AB  - OBJECTIVE: In 1998, the screening and treatment practices of certified nurse
      midwives (CNMs) for group B streptococcal (GBS) infection during pregnancy were
      studied and evaluated for their consistency with the 1996 perinatal GBS
      prevention guidelines of the Centers for Disease Control and Prevention (CDC).
      METHODOLOGY: Five hundred thirty-nine surveys were completed by CNMs attending
      the 1998 American College of Nurse-Midwives' Convention. Of these, 502 (94.7%)
      reported a practice policy for GBS prophylaxis. RESULTS: The Culture-Based
      Approach was used by 66.7% and the Obstetrical Risk Factor Approach by 28%. Most
      (69%) reported using multiple culture sites, most commonly the proximal vagina
      and anorectal area (33.2%), followed by the distal vagina and anorectal area
      (26.7%), and the anorectal area and proximal and distal vagina (7.1%). Most CNMs
      (92.5%) reported treating GBS intrapartally, with penicillin the most frequently
      reported antimicrobial (55.0%) used, and most (94.2%) reporting treatment through
      labor until birth. CONCLUSION: Overall, GBS prophylaxis practices among survey
      respondents comply with 1996 CDC recommendations; however, GBS screening
      practices show room for improvement and the need for continuing education that
      emphasizes the CDC guidelines, updates as they become available, and other new
      literature about the topic. In addition, heightened awareness among all perinatal
      providers is needed with respect to CDC guidelines, especially as they pertain to
      variations in culture sites, identification of risk categories, and the selection
      of appropriate antimicrobial treatment agents.

PMID- 11300303
TI  - Weaving the art and science of midwifery: "Oh, had I a golden thread...".

PMID- 11300304
TI  - Findings from the American College of Nurse-Midwives' annual membership survey,
      1995-1999.
AB  - American College of Nurse-Midwives (ACNM) membership data collected from 1995
      1999 offer a description of the evolution of the profession of midwifery, as
      shown in the characteristics of certified nurse-midwives and certified midwives,
      including basic demographics, practice characteristics, and employment
      components. During the period studied, slight increases were noted in age, number
      of years in practice, salary, and education level. Although the overall
      proportion of midwives of color did not change appreciably during the 5-year
      period, the absolute numbers of culturally diverse midwives increased. Student
      midwives were found to be younger and more culturally diverse than they were in
      the early 1990s. Data about midwifery practice provide valuable information to
      health care managers, educators, policy makers, legislators, and professional
      organizations, which may guide allocation of resources and reflect how members of
      the professions can influence access to health care for women and their families.

PMID- 11300305
TI  - Have we overlooked the most common cause of maternal mortality in the United
      States?

PMID- 11300306
TI  - Midwifery in Northern Belize.
AB  - During several volunteer experiences in the Corozal District in Northern Belize,
      the authors worked with and interviewed traditional midwives, midwife educators,
      administrators, and professional midwives, who practice in public health clinics,
      rural health outposts, and a government hospital. One interview with a
      traditional midwife from a rural Mayan village, garnered interesting information
      about her 63-year practice, which is compared with the practice of professional
      midwives. Issues important to midwifery and health care in Belize are discussed.
      The interviews and the authors' own experiences reveal changing birthing
      practices, as well as the continued importance of midwives in the care of
      childbearing women in Northern Belize.

PMID- 11300307
TI  - Hidden from view: violent deaths among pregnant women in the District of
      Columbia, 1988-1996.
AB  - OBJECTIVE: Maternal mortality is underreported in the United States in part
      because traumatic deaths are not included in nationally reported maternal
      mortality ratios. The overall study goal was to compare women whose deaths had
      been reported to and investigated by a medical examiner and who had evidence of
      pregnancy to women without evidence of pregnancy in terms of socio-demographic
      information, toxicology results, and manner and cause of death. A secondary goal
      was to compare the pregnancy status and gestational age of women with evidence of
      pregnancy at the time of death in relation to the manner of death, with
      particular focus on women who died as a result of violent death. METHODOLOGY:
      Autopsy charts from 1988-1996 for 651 women aged 15 to 50 from the District of
      Columbia Office of the Chief Medical Examiner whose autopsies included
      examination of the uterus were reviewed. Medical examiners' classification of
      manner and specific causes of death were used as the main outcome measures.
      Overall, the sample reflected demographic characteristics of women of
      childbearing age in the District of Columbia, with 82% black, 74.6% unmarried,
      and 46.5% aged 20 to 34. RESULTS: Among the 651 autopsy charts evaluated, 30
      (4.6%) documented evidence of pregnancy; 43.3% of the women who died due to
      homicide with evidence of pregnancy were not included in the 21 pregnancy-related
      deaths officially reported by the District of Columbia State Center for Health
      Statistics during the study period, and therefore, were also not included in
      national maternal mortality ratios. Although not statistically significant, 11%
      more homicides occurred among women with evidence of pregnancy as compared to non
      pregnant women. Pregnant women who died a violent death were significantly more
      likely than non-pregnant women to have died due to gunshot trauma. A significant
      proportion of pregnant women were < 21 weeks gestation at the time of their
      death. Additionally, women in this sample with evidence of pregnancy were over 3
      times more likely to have been teenagers compared to non-pregnant women.
      CONCLUSION: Medical examiner autopsy records identify violent pregnancy
      associated deaths, many of which occur early in pregnancy and are missed by other
      enhanced case-finding techniques that require a record of a birth or fetal death.
      These deaths are usually excluded from reported maternal mortality ratios. Few
      studies have evaluated the prevalence of homicide in women of childbearing age,
      yet understanding the extent of less commonly associated causes of death during
      pregnancy such as homicide, may lead to improved identification of preventable
      problems that contribute to maternal morbidity and mortality. This study, which
      sheds new light on the identifying and reporting of maternal mortality, and
      specifically on homicide as a form of violence toward pregnant women, should be
      of particular interest for all women's health providers, as well as public health
      professionals, researchers, and advocates who are interested in the design,
      development, and evaluation of prevention programs, especially those directed
      toward preventable problems such as domestic violence.

PMID- 11300308
TI  - To be a midwife in this millennium.

PMID- 11300309
TI  - "Who among us will listen?".

PMID- 11300310
TI  - "Who among us will listen?".

PMID- 11300311
TI  - "Who among us will listen?".

PMID- 11300312
TI  - Medical oncology in Europe: more efforts needed.

PMID- 11300313
TI  - "You've come a long way, baby".

PMID- 11300314
TI  - Nokia, Ericsson and others are happier...

PMID- 11300315
TI  - Cancer information under threat: the case for legislation.

PMID- 11300316
TI  - Neuro-oncology clinical trials: promise and pitfalls.

PMID- 11300317
TI  - Microsatellite instability: application in hereditary non-polyposis colorectal
      cancer.
AB  - Colorectal cancer (CRC) is a significant cause of mortality in Western
      populations. About 15% of CRC patients report a family history of the disease.
      Studies on individuals with a genetic predisposition to CRC have been responsible
      for significant advances in the understanding of this disease. Thus, although
      developments in molecular biology have been mainly restricted to a minority of
      individuals with a hereditary background, information obtained from this group
      may affect the diagnosis and therapy of sporadic CRCs as well. Deficiency in the
      DNA mismatch repair (MMR) system results in microsatellite instability (MSI).
      Individuals from hereditary non-polyposis colorectal cancer (HNPCC) kindreds with
      germline mutations in genes involved in MMR may benefit from clinical screening
      programs. The higher frequency of MSI in HNPCC than in sporadic tumours suggests
      that involvement of MMR genes in sporadic adenomas may be uncommon. Consequently

PMID- 11300318
TI  - Hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the sixth most common cancer of men and
      eleventh most common cancer of women world-wide. However, because almost every
      individual who develops liver cancer dies of the disease, HCC is the third most
      common cause of the cancer deaths in men and seventh most common in women. The
      treatment of choice for hepatocellular carcinoma remains surgical resection or
      liver transplantation, in carefully selected cases. In patients with
      hepatocellular carcinoma not amenable to surgical intervention a variety of
      different therapeutic interventions have been investigated. These include direct
      ablation of the tumour using agents such as ethanol or acetic acid, transcatheter
      arterial chemoembolization, or systemic chemotherapy. The evaluation of their
      efficacy is compromised by the paucity of adequately powered randomised clinical
      trials. The main challenge facing the research community over the next decade is
      to prioritise the most promising treatments and take these forward into
      multicentre controlled trials. Even if these fail to improve results, they will
      help reduce the variation in clinical practice by eliminating anecdotal
      treatment.

PMID- 11300319
TI  - Dietary glycemic load and colorectal cancer risk.
AB  - BACKGROUND: Insulin and insulin-like growth factors can stimulate proliferation
      of colorectal cells. High intake of refined carbohydrates and markers of insulin
      resistance are associated with colorectal cancer. To test the insulin/colon
      cancer hypothesis, we determined whether the dietary glycemic index and the
      glycemic load are associated with colorectal cancer risk. DESIGN: A case-control
      study on colorectal cancer conducted in Italy. Cases included 1125 men and 828
      women with histologically confirmed incident cancer of the colon or rectum.
      Controls were 2073 men and 2081 women hospitalized for acute conditions. We
      calculated average daily dietary glycemic index and glycemic load, and fiber
      intake from a validated food frequency questionnaire. RESULTS: Direct
      associations with colorectal cancer risk emerged for glycemic index (odds ratio
      (OR) in highest vs. lowest quintile = 1.7; 95% confidence interval (CI): 1.4-2.0)
      and glycemic load (OR = 1.8; 95% CI: 1.5-2.2), after allowance for
      sociodemographic factors, physical activity, number of daily meals, and intakes
      of fiber, alcohol and energy. ORs were more elevated for cancer of the colon than
      rectum. Overweight and low intake of fiber from vegetables and fruit appeared to
      amplify the adverse consequences of high glycemic load. CONCLUSIONS: The positive
      associations of glycemic index and load with colorectal cancer suggest a
      detrimental role of refined carbohydrates in the etiology of the disease.

PMID- 11300320
TI  - Single-agent oxaliplatin in pretreated advanced breast cancer patients: a phase
      II study.
AB  - PURPOSE: Oxaliplatin (L-OHP), a new platinum analogue, is an active drug in
      colorectal and ovarian cancer. In this phase II study we explored tolerability
      and activity of oxaliplatin as a single agent in metastatic breast carcinoma
      patients. PATIENTS AND METHODS: Fourteen anthracycline pretreated advanced breast
      cancer patients were enrolled. Oxaliplatin was given at 130 mg/m2 on day 1 and
      repeated every three weeks. Analysis of toxicity, response rate and survival was
      performed. RESULTS: The median number of courses per patient was four (range 2
      6). The median administered dose-intensity was 43.3 mg/m2/week (range 32.5-43.3)
      which represents 100% of projected dose-intensity. No severe toxicity was
      encountered. Three patients developed acute transient laryngeal symptoms. Three
      patients displayed a partial response (21%), (95% confidence interval (CI): 0%
      43%), two stable disease (14%) and nine progressed (64%). Response lasted five,
      four and five months respectively. Median survival was 12 months. CONCLUSIONS: In
      this limited experience, oxaliplatin appeared to be well tolerated and moderately
      active in advanced anthracycline-pretreated breast cancer patients. Combination
      chemotherapy with other active drugs such as 5-fluorouracil (5-FU),
      anthracyclines and taxanes should represent the next step of development of this
      new drug.

PMID- 11300321
TI  - Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract
      cancer.
AB  - BACKGROUND: Patients with advanced biliary tract carcinoma face a dismal
      prognosis as no effective palliative therapy has been defined. The aim of the
      present phase II investigation was to evaluate the therapeutic efficacy and
      tolerance of a two-weekly high-dose gemcitabine regimen in this patient
      population. PATIENTS AND METHODS: Thirty-two consecutive patients with locally
      unresectable or metastatic biliary tract cancer were enrolled in this multicenter
      phase II trial. Treatment consisted of gemcitabine 2200 mg/m2 given as a 30-min
      intravenous infusion every two weeks for a duration of six months unless there
      was prior evidence of progressive disease. RESULTS: After a median number of 12
      treatment courses, 7 of 32 (22%) patients had a partial response that lasted for
      a median duration of 6.0 months (range 3.5-10.0). Fourteen additional patients
      (44%) had stable disease, whereas eleven patients (34%) progressed despite
      therapy. The median time to progression was 5.6 months (range 1.8-13.0); median
      survival time was 11.5 months (range 3.0-24.0), and the probability of surviving
      beyond 12 months was 44%. The tolerance of treatment was remarkable with only two
      patients each experiencing grade 3 leukocytopenia, granulocytopenia and/or
      thrombocytopenia, and one patient had grade 3 anaemia. Similarly, nonhaematologic
      side effects were infrequent, and generally mild to moderate. CONCLUSIONS: Two
      weekly high-dose gemcitabine seems to represent a potentially effective, safe and
      well-tolerated regimen for the palliative treatment of patients with advanced
      biliary tract cancer.

PMID- 11300322
TI  - Use of the ratio of time to progression following first- and second-line therapy
      to document the activity of the combination of oxaliplatin with 5-fluorouracil in
      the treatment of colorectal carcinoma.
AB  - BACKGROUND: It has been proposed that the activity of a second-line treatment
      regimen can be documented by showing that the time to progression (TTP) following
      second-line therapy is longer than the TTP following first-line therapy in the
      same patients. PATIENTS AND METHODS: The ratio of TTP during first and second
      line therapy, identified as the growth modulation index (GMI), was determined in
      34 patients with advanced colorectal cancer. First-line chemotherapy consisted of
      one of several schedules of leucovorin (LV)-modulated 5-fluorouracil (5-FU) or
      raltitrexed. Second-line therapy consisted of the combination of LV-modulated 5
      FU and oxaliplatin (1-OHP). Patients were switched to second-line therapy upon
      evidence of progressive disease following first-line therapy. RESULTS: Median TTP
      following first-line therapy was 13 weeks (95% confidence interval (CI): 7.6
      18.7), while median TTP following second-line therapy was 31 weeks (95% CI: 21.3
      41.0). Sixteen patients (47%; 95% CI: 35%-59%), showed a GMI > or = 1.33, while
      the remaining 18 patients (53%; 95% CI: 40%-66%) had a GMI < 1.33. Log-rank
      analysis of the Kaplan-Meier curves of TTP following first- versus second-line
      therapy demonstrated a statistically significant difference in favour of second
      line therapy (P = 0.0081). CONCLUSIONS: This study demonstrates the utility of
      the GMI as a tool for assessing the activity of novel second-line therapeutic
      programs.

PMID- 11300323
TI  - Paclitaxel in combination with carboplatin as salvage treatment in refractory
      small-cell lung cancer (SCLC): a multicenter phase II study.
AB  - PURPOSE: The activity and toxicity of paclitaxel plus carboplatin combination in
      patients with disease progression after initial chemotherapy for small-cell lung
      cancer (SCLC) was investigated in a multicenter phase II study. PATIENTS AND
      METHODS: Thirty-two patients (twenty-seven men) with extensive stage refractory
      SCLC after EP or CAV front-line chemotherapy were treated with paclitaxel 200
      mg/m2 on day 1 and carboplatin 6 AUC on day 2 in a four-week schedule. The
      patients' median age was 60 years and the performance status (WHO) was 0 for 9, 1
      for 20 and 2 for 3 patients. All patients were evaluable for toxicity and 29 for
      response. RESULTS: Complete response was observed in one (3%) and partial
      response in seven (22%) for an overall response rate of 25% (95% confidence
      interval (CI): 10%-40%). Seven (22%) patients had stable disease and seventeen
      (53%) progressive disease. All but one of the responders had been previously
      treated with EP combination and three of them had failed to respond. The median
      duration of response and the median TTP were 3 and 5.5 months, respectively. The
      median overall survival was seven months. Grade 3-4 neutropenia was observed in
      12 (37%) patients and in 2 of these it was associated with infection. There were
      no toxic deaths. Grade 4 anaemia was observed in one (3%) patient and grade 3
      thrombocytopenia in three (9.4%). Non-hematologic toxicity was very mild with
      grade 2-3 asthenia occurring in 10 (25%) patients; asthenia was the reason for
      treatment discontinuation in 3 patients. CONCLUSIONS: The combination of
      paclitaxel and carboplatin is a relatively active and well-tolerated regimen as
      salvage treatment in patients with refractory SCLC.

PMID- 11300324
TI  - Docetaxel and cisplatin in locally advanced or metastatic squamous-cell carcinoma
      of the head and neck: a phase II study of the Southern Italy Cooperative Oncology
      Group (SICOG).
AB  - BACKGROUND: Docetaxel is one of the most promising new drugs against squamous
      cell carcinoma of the head and neck (SCCHN), while cisplatin is one of the most
      active single agents. A phase I study has shown the feasibility of the
      combination of the two drugs, and activity in SCCHN has been seen. PATIENTS AND
      METHODS: Patients with locally advanced, inoperable, or metastatic SCCHN, never
      pretreated with radiotherapy or chemotherapy, received three courses of docetaxel
      75 mg/m2 and cisplatin 100 mg/m2, every three weeks. Thereafter, responsive
      metastatic patients received additional chemotherapy, while patients with locally
      advanced disease underwent radiation therapy. RESULTS: Forty-six patients (forty
      five with locally advanced, one with metastatic disease) were entered into the
      study. Ten patients did not complete three courses of chemotherapy because of
      early death; one patient discontinued treatment after one course. Twenty-one
      objective responses were observed (46%, 95% confidence interval (CI): 31%-60%),
      including five complete responses (11%) and sixteen partial responses (35%).
      Following induction chemotherapy plus radiation therapy, 9 of 21 evaluable
      patients were rendered disease free, while 8 additional patients had a partial
      response. After a median follow-up of 18 months, the median duration of response
      was 12 months, (range 3-25+), and the median overall survival was 11 months. Six
      early deaths were considered possibly treatment-related (sepsis following grade 4
      neutropenia in two cases, hypovolemic shock following severe diarrhea in four
      cases). Neutropenia was the most severe toxicity (grade 3-4 in 28 patients,
      median duration 4 days); diarrhea and vomiting were the most troublesome non
      haematologic toxicities (grade 4 in 4 and 3 patients, respectively). CONCLUSIONS:
      The combination of docetaxel and cisplatin is active in SCCHN, but toxicity is
      substantial. This schedule does not appear to offer any advantage compared with
      conventional regimens.

PMID- 11300325
TI  - Acute myeloid leukemia in patients previously diagnosed with breast cancer:
      experience of the GIMEMA group.
AB  - OBJECTIVE: To evaluate in a multicenter retrospective study, the clinical and
      laboratory characteristics and the outcome of patients with acute myeloid
      leukemia (sAML) previously diagnosed with breast cancer (BC) among an adult acute
      leukemia population. PATIENTS AND METHODS: Between June 1992 and July 1996, 3934
      new cases of adults with acute leukemia were recorded in GIMEMA Archive of Adult
      Acute Leukemia (2964 AML, 901 ALL, 69 acute leukemia expressing both myeloid and
      lymphoid surface markers). RESULTS: Two hundred patients (5.1%) presented with a
      history of previous malignancy (21 of them were affected by ALL and 179 by AML).
      Among sAML, 37 patients (29%) had a previous breast cancer. They consisted of 36
      females and 1 male, median age 56 years, range 34-87. The median latency between
      the 2 malignancies was 54 months (range 5-379). Twenty-seven patients received
      chemo- and/or radiotherapy for breast cancer (7 only chemotherapy, 6 only
      radiotherapy, and 14 combined treatment). All patients were surgically treated
      but in 10 patients surgical debridement was the sole therapy for breast cancer.
      The drugs most frequently employed were alkylating agents (18 patients),
      topoisomerase II inhibitors (9 patients), antimetabolites (20 patients) (CMF, CEF
      and MMM combinations). At onset of sAML the median WBC count was 7.7 x 10(9)/l
      (0.8-153) and the median platelet count was 33.5 x 10(9)/l (3-305). Considering
      morphological features, FAB subtypes were 4 M0, 5 M1, 11 M2, 5 M3, 8 M4, 3 M5,
      and 1 M6. Cytogenetic study was performed on 28 patients and 12 of them presented
      abnormalities. It is noteworthy that chromosome 5 or 7 abnormalities (typically
      observed in those patients treated with alkylating agents) were present only in
      three cases. Thirty-four patients received chemotherapy for sAML, and twenty-five
      of them achieved a CR (74%), with a median duration of twenty-eight weeks (5
      280+). The overall survival was 8 months (1-80+). DISCUSSION: The high number of
      sAML we observed in patients with a previous breast cancer, may be due to the
      fact that this malignancy is the most frequent neoplasm in women and by the high
      probability of cure with a consequent long disease-free survival. Our results
      suggest that the risk of sAML after recovery from breast cancer is increasing due
      to the rise in the number of patients cured from breast cancer, and in the future
      could be a relevant problem for haematologists.

PMID- 11300326
TI  - 5-Fluorouracil induced Fas upregulation associated with apoptosis in liver
      metastases of colorectal cancer patients.
AB  - BACKGROUND: In vitro, thymidylate synthase (TS) inhibition by 5-fluorouracil (5
      FU) induces thymineless apoptosis possibly via Fas receptor Fas ligand
      interactions and cell-cycle arrest. In colorectal cancer patients we evaluated
      whether 5-FU administration also resulted in apoptosis and cell-cycle arrest and
      which proteins might be involved. PATIENTS AND METHODS: Biopsy specimens were
      taken from 36 patients 2, 22 or 46 hours after administration of 500 mg/m2 5-FU,
      and from 12 control patients who did not receive 5-FU. In frozen tissue-sections
      from liver metastases immunohistochemistry was performed with antibodies directed
      against p53, p21, E2F2, Rb, Ki67 and TS (cell-cycle related) and bax, BCL-2, BCL
      x, mcl-1, PARP, caspase-3, Fas receptor and Fas ligand (apoptosis related).
      Apoptosis was determined by M30 immunostaining, which recognises a cleavage
      product of cytokeratin 18. RESULTS: Fas receptor expression was 50% higher (P =
      0.036) 46 hours after 5-FU administration compared to the control group. This was
      associated with a 12% increase (P < 0.02) in M30 positive tumour cells and with
      elevation of caspase-3 and PARP expression. The expression of Ki67 and E2F2 was
      30% lower after 46 hours compared to the control group, whereas TS was 56% lower
      after 2 hours and 32% higher again after 46 hours. No differences in the
      expression of the other proteins were found. CONCLUSIONS: These results suggest
      that 5-FU decreases proliferation status and induces apoptosis possibly via the
      Fas pathway. Since Fas mediated cell killing is important for cytotoxic T cells
      this indicates that clinical studies combining immunotherapy for activation of T
      cells and chemotherapy using 5-FU might be very effective.

PMID- 11300327
TI  - Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of
      haematologic toxicity.
AB  - BACKGROUND: The incidence of haematologic toxicity of valproate (VPA) ranges from
      1% to 32% and consists mainly of asymptomatic, dose-dependent thrombopenia. We
      describe a potentiation of haematologic side-effects of nitroso-urea (NU) when
      prescribed in association with VPA. PATIENTS AND METHODS: We followed a cohort of
      70 patients (58 men, 22 women, mean age: 56 years, range 20-75 years). Patients
      with high-grade gliomas were treated with up-front chemotherapy regimen
      consisting of fotemustine (d3: 100 mg/m2), cisplatin (d1-3: 33 mg/m2) and
      etoposide (d1-3: 75 mg/m2) followed by whole brain radiotherapy at progression.
      Sixty patients required anti-epileptic drugs (AED) for either a single, well
      documented epileptic seizure, or immediatly initiated after neurosurgical
      procedures. AED included VPA (35 of 60), phenobarbital (PB) (17 of 60),
      carbamazepine (CBZ) (2 of 60) and phenytoin (PHT) (3 of 60). Two patients had
      both PB and CBZ and one PB and PHT. RESULTS: Haematologic toxicity (grade 3-4
      thrombopenia, neutropenia or both) was observed in 37 of 70 (52.85%) patients.
      Among them 24 (65%) had VPA. Group C were patients treated with fotemustine alone
      with or without VPA (23 patients). CONCLUSION: When prescribed in association
      with a fotemustine-cisplatin regimen, VPA treatment results in a three-fold
      higher incidence of reversible thrombopenia, neutropenia or both. Haematologic
      side-effects decrease after AED modification during the continued chemotherapy.
      This adverse event should be managed with caution.

PMID- 11300328
TI  - CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal
      cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour
      infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).
AB  - BACKGROUND: There have been contradictory reports on the benefit of CEA and CA 19
      9 measurements in patients with metastatic colorectal cancer using palliative
      chemotherapy. The object of this study was to examine the diagnostic accuracy of
      monitoring of palliative chemotherapy by means of CEA and CA 19-9. PATIENTS AND
      METHODS: The tumour markers CEA and CA 19-9 were subjected to serial measurement
      in patients with metastatic colorectal cancer (n = 90) using palliative first
      line chemotherapy with weekly 24-hour infusion of high-dose 5-FU with FA and were
      compared with objective response according to WHO criteria. 85 patients could be
      evaluated. 43 patients (51%) initially had elevated CEA (> or = 10 ng/ml) and 33
      patients (39%) elevated CA19-9 (> or = 50 IE/ml). In 24 patients (28%), both
      markers were initially increased. With CEA positive patients, 143 cycles of
      chemotherapy were carried out, which showed the following response in the various
      cycles: 21 episodes with progressions (ePD), 69 episodes with no change (eNC), 53
      episodes with partial/complete remission (ePR/eCR). With CA 19-9 positive
      patients, 100 cycles of chemotherapy were carried out with the following results:
      21 episodes with progressions (ePD), 48 episodes with eNC, and 31 episodes with
      ePR/eCR. RESULTS: A CEA rise by at least 50% differentiated between ePD versus
      eNC/ePR/eCR with a sensitivity of 76% and specificity of 90%. With CEA decreases
      of at least 30% in 99% of these patient episodes (78 of 79), a tumour progression
      could be excluded. Patients with an initial drop in CEA after the first cycle of
      chemotherapy of at least 50% of the initial level had a significantly higher
      probability of achieving an ePR/eCR in further therapy (relative risk 2.9; P =
      0.002). With an CA 19-9 increase of at least 30%, a sensitivity progression of
      62% and a specifity of 90% could be calculated. A CA 19-9 decrease of at least
      60% excludes a progression in 95% of the patient episodes. CONCLUSIONS: A CEA or
      CA 19-9 rise is only conditionally appropriate for recording progressions. A
      progression however, can be excluded with falling levels with high diagnostic
      accuracy, in which CEA offers a greater degree of certainty than CA 19-9. With a
      drop in CEA 79 of 143 (= 55%) of the CT scans could be saved, in which case 78 of
      79 patient episodes (99%) were correctly assessed as 'no progression'. In
      patients with an increased CEA and CA 19-9 the CEA determination is sufficient
      for the further monitoring. A confirmation of these results by multicenter trials
      can result in a considerable decrease of monitoring costs for palliative
      treatment.

PMID- 11300329
TI  - Octreotide in the treatment of severe chemotherapy-induced diarrhea.
AB  - BACKGROUND: Chemotherapy-induced diarrhea (CID) is a common side effect of a
      number of chemotherapeutic agents. Conventional therapy for severe CID with
      opioids or loperamide is moderately effective. A prospective trial was conducted
      using octreotide acetate for treatment of severe CID refractory to loperamide.
      PATIENTS AND METHODS: Thirty-two patients with grade 2 and 3 CID refractory to
      loperamide were treated with octreotide at a dosage of 100 microg subcutaneously
      3x/day for three days followed by 50 microg 3x/day for three days. Previous
      chemotherapy consisted of regimens containing fluorouracil, leucovorin, CPT-11,
      cyclophosphamide, methotrexate and cisplatin. Primary tumors were colorectal (n =
      23), gastric (n = 3), and other cancers (n = 6). RESULTS: Complete resolution of
      diarrhea was obtained in 30 of 32 patients (94%); 5 within 24 hours, 14 within 48
      hours, and 11 within 72 hours of treatment. Nineteen patients were treated as
      outpatients. Thirteen were hospitalized for a median of three days. Response was
      unaffected by age, gender, performance status, previous chemotherapy or primary
      tumor site. No side effects related to octreotide were observed. CONCLUSIONS:
      Octreotide 100 microg subcutaneously 3x/day for three days is an effective, safe
      treatment for CID given primarily or as a second-line therapy after loperamide
      failure.

PMID- 11300330
TI  - Response to chemotherapy is a major parameter-influencing long-term survival of
      metastatic breast cancer patients.
AB  - BACKGROUND: In cancer patients, correlation between response to chemotherapy and
      gain in survival remains debated. We addressed this question in a multivariate
      analysis evaluating response to chemotherapy as a factor influencing survival of
      patients with metastatic breast cancer. PATIENTS AND METHODS: From 1977 to 1992,
      1430 patients included in eight consecutive prospective trials of anthracycline
      based first-line chemotherapy in metastatic breast cancer, were available for
      assessment. Median follow-up was 155 months. RESULTS: Median survival from the
      date of randomisation was 24 months. Objective response rate was 63.6%. A
      complete response (CR) was achieved in 17% (249 patients). In a stepwise forward
      progression analysis objective response was the first independent prognostic
      factor for survival. Median survival time was 43 months for complete responders
      (CR), 29 months for partial responders (PR), 18 months for stable disease (SD), 5
      months for progressive disease (PD). The probability of survival at 5 and 10
      years was 35% and 15% for CR's and decreased to 18% and 6% for PR's. The timing
      of best response (at 4 or 8 months) was not related to outcome. CONCLUSIONS:
      Response to an anthracycline-based chemotherapy is a major independent prognostic
      factor in metastatic breast cancer. The use of this factor to investigate new
      drugs seems to be pertinent. The good prognosis of complete responders justifies
      further evaluation of new treatment strategies for this patient population.

PMID- 11300331
TI  - Vascular endothelial growth factor expression, S-phase fraction and thymidylate
      synthase quantitation in node-positive colon cancer: relationships with tumor
      recurrence and resistance to adjuvant chemotherapy.
AB  - BACKGROUND: The behaviour of colorectal carcinomas may depend on molecular
      properties of tumors. In node-positive colon cancer, we assessed the S-phase
      fraction (SPF) index, the vascular endothelial growth factor (VEGF) expression
      and the TS levels. The combined analysis of SPF/VEGF was studied for predictivity
      of recurrent disease, the TS quantitation was related to the efficacy of
      fluorouracil-based adjuvant chemotherapy. PATIENTS AND METHODS: Consecutive
      patients with surgically-resected, node-positive colon cancer were studied. Flow
      cytometry for the SPF and immunohistochemistries for the TS and the VEGF
      expression were carried out on the primary tumor. Recurrences had to be proven by
      biopsy or surgery, and they were categorized as early, if occurred within 12
      months after surgery, or late if occured 13 months or more. RESULTS: Of 150
      evaluable patients, 100 had received fluorouracil-based adjuvant chemotherapy and
      50 control patients were untreated. The combined analysis of the VEGF and the SPF
      showed a strong association between the two markers; 48 patients (32%) had high
      SPF/VEGF positive tumors and 69 patients (46%) had low SPF/VEGF negative tumors
      (P < 0.0001). The majority of disease-free patients (73.4%) showed VEGF
      negative/low SPF tumors (P < 0.0001). Early recurrences occurred more frequently
      in patients with VEGF positive/high SPF tumors (P < 0.001). In the 100 patients
      treated with adjuvant chemotherapy, 86% of relapsed patients had TS
      overexpressing tumors and 69% of disease-free patients had TS negative tumors (P
      < 0.001). Also, early recurrences occurred more frequently in TS overexpressing
      tumors (P < 0.0001). CONCLUSIONS: Evidence is supported that node-positive colon
      cancer constitutes a heterogenous disease. Patients with VEGF positive/high SPF
      tumors showed an unfavourable outcome compared to patients with VEGF negative/low
      SPF tumors. The efficacy of fluorouracil-based adjuvant chemotherapy may depend
      on the TS status.

PMID- 11300332
TI  - Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin.
AB  - BACKGROUND: Quercetin is a naturally occurring flavonoid with many biological
      activities including inhibition of a number of tyrosine kinases. A phase I, dose
      escalation trial of quercetin defined the maximum tolerated dose (MTD) as 1700
      mg/m2 three weekly, but the vehicle, dimethyl sulphoxide (DMSO) is unsuitable for
      further clinical development of quercetin. PATIENTS AND METHODS: A water-soluble,
      pro-drug of quercetin (3'(N-carboxymethyl)carbomyl-3,4',5,7-tetrahydroxyflavone),
      QC12 has been synthesised. Six cancer patients received 400 mg of QC12
      (equivalent to 298 mg of quercetin), orally on day 1 and intravenously (i.v.) in
      normal saline on day 14. RESULTS: Following oral administration of QC12 we were
      unable to detect QC12 or quercetin in plasma. After i.v. administration, we
      detected peak plasma concentrations of QC12 of 108.7 +/- 41.67 microMolar
      (microM). A two-compartment model with mean t(1/2)alpha of 0.31 +/- 0.27 hours
      and mean t(1/2)beta of 0.86 +/- 0.78 hours best described the concentration-time
      curves for QC12. The mean AUC was 44.54 +/- 13.0 microM.hour and mean volume of
      distribution (Vd) of 10.0 +/- 6.2 litres (l). Quercetin was found in all patients
      following i.v. infusion of QC12, with peak levels of quercetin 19.9 +/- 11.8
      microM. The relative bioavailability of quercetin was estimated to be 20%-25%
      quercetin released from QC12. CONCLUSIONS: QC12 is not orally bioavailable. This
      water-soluble pro-drug warrants further clinical investigation; starting with a
      formal phase I, IV, dose-escalation study.

PMID- 11300333
TI  - Phase II study of temozolomide in heavily pretreated cancer patients with brain
      metastases.
AB  - PURPOSE: To determine the efficacy, tolerability, and safety of temozolomide in
      heavily pretreated patients with solid tumors and brain metastases. PATIENTS AND
      METHODS: Twenty-seven of twenty-eight enrolled patients with brain metastases
      from solid tumors received temozolomide (150 mg/m2/day for five days every 28
      days). Twelve patients had non-small-cell lung cancer, five patients had small
      cell lung cancer, four patients had breast cancer, and seven patients had other
      solid tumors. The majority of the patients had multiple metastatic sites, a poor
      performance status, and had been heavily pretreated. The primary end points were
      objective response rate, time to progression, and overall survival. Secondary end
      points included safety and tolerability, and neurologic performance status.
      RESULTS: A partial response was achieved in 1 (4%) of 24 evaluable patients.
      Disease stabilization was observed in four (17%) patients. Overall median
      survival was 4.5 months and median time to progression was 3 months. Improvements
      in clinical neurologic status were achieved in 10 (37%) patients. Treatment with
      temozolomide was well tolerated. Four patients had grade 3 nausea and vomiting.
      No grade 4 toxicity or treatment-related deaths were observed. CONCLUSIONS:
      Temozolomide demonstrated encouraging activity in the treatment of brain
      metastases in heavily pretreated patients with solid tumors, and was safe and
      well tolerated.

PMID- 11300334
TI  - Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a
      phase II study.
AB  - BACKGROUND: To investigate the efficacy of temozolomide in relation to response
      rate, toxicity, time to progression. and median survival time, a phase II study
      was conducted in patients with recurrent high-grade glioma following surgery plus
      radiotherapy and first-line chemotherapy based on nitrosourea, procarbazine and
      vincristine. PATIENTS AND METHODS: Forty-one patients with high-grade glioma, at
      second recurrence or progression, of which twenty-two (54%) had glioblastoma
      multiforme, ten (24%) anaplastic astrocytoma, and nine (22%) anaplastic
      oligodendroglioma were administered temozolomide, 150 mg/m2/daily for five days
      every four weeks. RESULTS: Response was assessed in 40 patients. The overall
      response rate (complete + partial response) was 22.5% (95% confidence interval
      (CI): 9.5%-35%). The median time to progression for all 41 patients was 22.3
      weeks; progression-free survival at 6 and 12 months was 48.5% and 34.7%,
      respectively. Median survival time was 37.1 weeks with 80.2% at 6 and 34.9%
      survival at 12 months. CONCLUSIONS: On multivariate analysis, response to
      previous treatment was significant (P = 0.03) for time to progression and
      Karnofsky performance score for overall survivall (P = 0.002). Temozolomide gave
      a moderate response rate with acceptable toxicity as second-line chemotherapy in
      patients with recurrent high-grade glioma.

PMID- 11300336
TI  - Myeloid metaplasia of the breast.
AB  - Hereby, we present the case of a 50-year-old woman with 5-year history of chronic
      idiopathic myelofibrosis who was referred to our institution after she had noted
      a lump in the breast. Histological examination of the lesion removed from her
      left breast yielded the diagnosis of extramedullary hematopoiesis in the breast.
      On the basis of our experience in this particular patient and on the basis of the
      data in the literature, we discuss the value of different more or less invasive
      diagnostic procedures, such as sonography, mammography, fine needle aspiration
      biopsy and surgical excision with histological examination of removed tissue in
      obtaining the diagnosis of myeloid metaplasia in breast.

PMID- 11300335
TI  - Multicenter phase II trial of temozolomide in patients with glioblastoma
      multiforme at first relapse.
AB  - BACKGROUND: Recurrent glioblastoma multiforme (GBM) is resistant to most
      therapeutic endeavors, with low response rates and survival rarely exceeding six
      months. There are no clearly established chemotherapeutic regimens and the aim of
      treatment is palliation with improvement in the quality of life. PATIENTS AND
      METHODS: We report an open-label, uncontrolled, multicenter phase II trial of
      temozolomide in 138 patients (intent-to-treat [ITT] population) with glioblastoma
      multiforme at first relapse and a Karnofsky performance status (KPS) > or = 70.
      One hundred twenty-eight patients were histologically confirmed with GBM or
      gliosarcoma (GS) by independent central review. Chemotherapy-naive patients were
      treated with temozolomide 200 mg/m2/day orally for the first five days of a 28
      day cycle. Patients previously treated with nitrosourea-containing adjuvant
      chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle. In
      the absence of grade 3 or 4 toxicity, patients on the 150 mg/m2 dose schedule
      were eligible for a 200 mg/m2 dose on the next cycle. RESULTS: The primary
      endpoint was six-month progression-free survival assessed with strict
      radiological and clinical criteria. Secondary endpoints included radiological
      response and Health-related Quality of Life (HQL). Progression-free survival at
      six months was 18% (95% confidence interval (CI): 11%-26%) for the eligible
      histology population. Median progression-free survival and median overall
      survival were 2.1 months and 5.4 months, respectively. The six-month survival
      rate was 46%. The objective response rate (complete response and partial
      response) determined by independent central review of gadolinium-enhanced
      magnetic resonance imaging (MRI) scans was 8% for both the ITT and eligible
      histology populations, with an additional 43% and 45% of patients, respectively,
      having stable disease (SD). Objectively assessed response and maintenance of a
      progression-free status were both associated with HQL benefits (characterized by
      improvements over baseline in HQL domains). Temozolomide had an acceptable safety
      profile, with only 9% of therapy cycles requiring a dose reduction due to
      thrombocytopenia. There was no evidence of cumulative hematologic toxicity.
      CONCLUSIONS: Temozolomide demonstrated modest clinical efficacy, with an
      acceptable safety profile and measurable improvement in quality of life in
      patients with recurrent GBM. The use of this drug should be explored further in
      an adjuvant setting and in combination with other agents.

PMID- 11300337
TI  - Sustained response of sarcomatoid renal-cell carcinoma to MAID chemotherapy: case
      report and review of the literature.
AB  - The sarcomatoid variant of renal-cell carcinoma (SRCC), a clinically aggressive
      subtype of renal parenchymal tumors, is typically resistant to systemic
      treatments and carries a poor prognosis. The authors report a case of a 57-year
      old male with advanced SRCC who had a durable complete response after MAID
      (mesna, adriamycin, ifosfamide and dacarbazine) chemotherapy, and remains free of
      disease four years after completing treatment. To the authors' knowledge, this is
      the first report of a remission from MAID chemotherapy in SRCC. A review of
      published literature revealed occasional responses after systemic chemotherapy.
      Notably, all responses were seen with doxorubicin containing regimens, suggesting
      that doxorubicin is a critical component in chemotherapy regimens for SRCC.

PMID- 11300338
TI  - Complete response of an HIV negative gastric Kaposi's sarcoma (KS) patient with
      peritoneal carcinomatosis by liposomal daunorubicin treatment.
AB  - We report the first case of an HIV negative patient with gastric Kaposi's sarcoma
      (KS) and peritoneal carcinomatosis in whom a complete response (CR) was obtained
      after liposomal daunorubicin administration. The patient presented with
      epigastric pain and hematemesis. Upper gastric endoscopy with multiple biopsies
      showed gastric involvement by KS. The whole physical examination and the thoraco
      abdomino-pelvic CT scans showed no other localization. A total gastrectomy was
      performed. Histological examination confirmed the diagnosis of KS with
      involvement of regional lymph nodes and peritoneal lesions. Six cycles of
      liposomal daunorubicin were given. Post-treatment coelioscopic control was
      normal. The patient received another six adjuvant cycles of liposomal
      daunorubicin. The patient is in complete remission six months after the end of
      treatment. Liposomal daunorubicin is a promising treatment in the non HIV patient
      with visceral KS.

PMID- 11300339
TI  - Severe prognosis of signet-ring cell adenocarcinoma occurring in Meckel's
      diverticulum.

PMID- 11300340
TI  - Representation on International Scientific Committees.

PMID- 11300341
TI  - Combination chemotherapy for colon cancer: de gustibus non est disputandum.

PMID- 11300342
TI  - Hydroxyurea promotes the reduction of spontaneous BFU-e to normal levels in SS
      and S/beta thalassemic patients.
AB  - We have studied the effects of hydroxyurea on growth and differentiation of early
      erythroid progenitor cells (BFU-e) from peripheral blood of sickle cell disease
      patients (five SS and two Hb S/beta-thalassemia) in the presence or absence of
      exogenous stimulating factors. When the mononuclear cells from the sickle cell
      disease patients were cultured at diagnosis (before hydroxyurea treatment), there
      was an increased number of BFU-e in relation to controls (p < 0.05, Wilcoxon
      test) when cells were grown in the presence or absence of 5637 conditioned medium
      and erythropoietin. Colonies that developed in the absence of added growth
      factors were considered "spontaneous". A significant difference was observed
      after hydroxyurea treatment in the number of BFU-e obtained in the presence and
      absence of stimulus, with a higher reduction in the spontaneous BFU-e number. As
      expected, there was an increased Hb F level in these patients when compared with
      their pretreatment levels. There was no correlation between spontaneous BFU-e and
      hemoglobin levels in all patients studied.

PMID- 11300343
TI  - Novel beta-thalassemia mutation in a beta-thalassemia intermedia patient.

PMID- 11300344
TI  - Hb Tsukumi [beta117(G19)His-->Tyr] found in a Moroccan woman.

PMID- 11300345
TI  - A rare case of osteomyelitis of the sternum in an adult with sickle cell disease.

PMID- 11300347
TI  - Hematological and molecular analysis of beta-thalassemia and Hb Lepore in
      Campania, Italy.
AB  - This epidemiological study was based on a hematological and a molecular analysis
      of 310 heterozygous beta thalassemic and 75 carriers of Hb Lepore out of 3,000
      microcythemic subjects from the Campania region of Italy. The molecular analysis
      of beta chains and the deltabeta hybrid gene has shown different beta chain
      defects, but only the Hb Lepore-Boston-Washington type in association with
      haplotypes I and V. The prevalence and distribution of these molecular defects in
      Campania show that they are linked to historical events and to the geographical
      characteristics of this region.

PMID- 11300346
TI  - Prenatal diagnosis of beta-thalassemia major by high-performance liquid
      chromatography analysis of hemoglobins in fetal blood samples.
AB  - In Thailand and adjacent countries, most of the beta-thalassemia genes are
      beta(0)-thalassemia mutations that prevent the production of Hb A. We propose the
      quantitation of the Hb A fraction in fetal blood in the mid-trimester of
      pregnancy by automated high performance liquid chromatography as a reasonable
      prenatal diagnostic method to be applied in areas with limited laboratory
      facilities. Forty pregnant women at risk of delivering a child with beta
      thalassemia major were identified using an erythrocyte osmotic fragility test and
      quantitation of Hb A2. Cordocentesis was performed at the gestational age of 18
      22 weeks and fetal blood was analyzed for hemoglobin fractions by automated high
      performance liquid chromatography. The beta-globin gene mutations were
      characterized by beta-globin gene sequencing. The 4 bp deletion at codons 41/42 (
      TTCT) was the most frequent of the 40 beta-thalassemia mutations observed (20/40
      = 50%), followed by the splice site mutation IVS-I-1 (G-->T) (7/40 = 17.5%), the
      nonsense mutation at codon 17 (A-->T) (7/40 = 17.5%), the nonsense mutation at
      codon 35 (C-->A) (3/40 = 7.5%), and the beta(+)-thalassemia promoter mutation at 
      28 (A-->G) (3/40 = 7.5%). High performance liquid chromatography revealed nine
      fetuses which had only Hb F and no Hb A. All were homozygotes or compound
      heterozygotes for beta(0)-thalassemia mutations. In the remaining 31 fetuses, a
      Hb A peak was present in the chromatograms. One fetus with 0.5% Hb A was a
      compound heterozygote for the -28 (A-->G) and codons 41/42 (-TTCT) mutations. In
      the remaining 30 fetuses, the Hb A values ranged between 0.8 and 7.4%. Twenty of
      these, with a Hb A concentration of 1.82 +/- 0.49% (range 0.8-2.8%), were beta
      thalassemia heterozygotes. The remaining 10 fetuses had Hb A values of 4.89 +/-
      1.47% (range 2.9-7.4%) and normal beta-globin genes. The absence of Hb A in
      homozygotes or compound heterozygotes for beta(0)-thalassemia mutations and the
      presence of measurable amounts of Hb A in heterozygotes and normal homozygotes,
      permits the diagnosis of fetuses expected to develop postnatal beta-thalassemia
      major.

PMID- 11300348
TI  - Molecular spectrum of beta-thalassemia in the Iranian Province of Hormozgan.
AB  - Prevention of beta-thalassemia implies knowledge of the molecular spectrum
      occurring in the population at risk. This knowledge is necessary, especially when
      a prevention protocol is applied to a multiethnic population. For this purpose,
      we have recently analyzed a large population of Iranian patients living in the
      Province of Hormozgan in Iran, and a small group of Iranian patients living in
      The Netherlands. We have found a different mutation spectrum in both populations
      as compared to the data obtained by other authors for the Iranian regions of
      Tehran, Fars, Sistan Balouchestan, Bushehr, and Khouzestan. The IVS-I-5 (G-->C)
      is the most frequent mutant in the province of Hormozgan (69%), followed by the
      IVS-II-1 (G-->A) (9.6%), while the IVS-I-1 (G-->A) was the most frequent defect
      found in the Iranian population sample in The Netherlands. The IVS-II-745 (C-->G)
      mutation in cis with the 5'UTR (untranslated region) +20 (C-->T) transition was
      observed in two unrelated, transfusion-dependent homozygotes, living in the
      Hormozgan Province where, in contrast with populations living in other provinces
      of Iran, no IVS-I-110 (G-->A) or IVS-I-1 (G-->A) mutations were found. We report
      the molecular spectra of our population samples and compare them with the
      mutation spectra observed in the Iranian populations by other authors. We discuss
      the severe phenotype of the patients homozygous for the IVS-II-745 (C-->G)
      mutation, linked in cis to the 5'UTR +20 (C-->T) transition. Molecular analysis
      using commercial kits is briefly compared with denaturing gradient gel
      electrophoresis, emphasizing the value of a rapid method of detection for
      molecular defects in areas where many mutations occur.

PMID- 11300349
TI  - Hb Sitia [beta128(H6)Ala-->Val]: an unstable variant with a substitution in the
      alpha1beta1 interface.
AB  - Hb Sitia [beta128(H6)Ala-->Val] was found in a Greek female with slightly reduced
      red blood cell indices. The abnormal hemoglobin was indistinguishable from Hb A
      by electrophoresis but eluted after Hb A on cation exchange high performance
      liquid chromatography. DNA sequence analysis revealed a GCT-->GTT mutation at
      codon 128, which is predicted to encode an Ala-->Val substitution. This was
      confirmed by mass spectrometry analyses of the beta-globin chain. Since alanine
      at beta128(H6) interacts with several amino acids of the alpha1beta1 contact, its
      replacement by a larger residue results in a mild instability of the molecule and
      slight modifications of the oxygen binding properties.

PMID- 11300350
TI  - Hb Mont Saint Aignan [beta128(H6)Ala-->Pro]: a new unstable variant leading to
      chronic microcytic anemia.
AB  - Hb Mont Saint-Aignan [beta128(H6)Ala-->Pro] is a mildly unstable variant,
      associated with hemolytic anemia, marked microcytosis and increased alpha/beta
      biosynthetic ratio (1.55 versus 1.1 +/- 0.1 in the control). The abnormal chain
      was isolated by selective precipitation with isopropanol and the structural
      modification determined by protein chemistry methods (reversed phase high
      performance liquid chromatography and mass spectrometry). Possible mechanisms
      underlying the beta(+)-thalassemia-like expression of this variant are discussed.

PMID- 11300351
TI  - Identification of Hb Villejuif [beta123(H1)Thr-->Ile] in Southern Italy.
AB  - Hb Villejuif [beta123(H1)Thr-->Ile] is a silent and asymptomatic variant
      described in 1989 in an 87-year-old woman of French origin suffering from
      coincidental polycythemia vera. This paper reports the second observation of Hb
      Villejuif in three related subjects from Montesarchio, Southern Italy. All
      routine techniques for hemoglobin analysis yielded normal results with the
      exception of a slight increase in the Hb A2 value. The occurrence of a variant
      beta-globin was rapidly assessed by liquid chromatography mass spectrometric
      analysis and the abnormal chain purified by high performance liquid
      chromatography. The amino acid replacement Thr-->Ile at beta123 was determined by
      tandem electrospray mass spectrometric analysis of the tryptic digest of the
      variant beta chain. The corresponding DNA mutation was established as C-->T at
      the second position of codon 123 (ACC-->ATC) by polymerase chain reaction
      amplification techniques.

PMID- 11300352
TI  - A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham
      N.C./Brescia.
AB  - We describe the molecular and the hematological characteristics of a Korean
      family with a dominantly inherited beta-thalassemia. Carriers were characterized
      by moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F levels,
      and splenomegaly. DNA analysis revealed a CTG (Leu) to CCG (Pro) substitution at
      codon 114 of the beta-globin gene, that leads to a highly unstable hemoglobin
      variant, Hb Durham-N.C./Brescia, and this was linked to the beta haplotype V, [+-
      --+-], and framework 2. RNA analysis showed that the proband had comparable
      levels of mutant and normal beta-mRNA. Translation of the mutant mRNA would give
      rise to non-functional hyperunstable beta-globin chains, and their degradation
      would, by placing an additional burden on the proteolytic process of the red
      blood cell precursors, result in a more severe phenotype.

PMID- 11300353
TI  - Clinical and hematological responses to hydroxyurea in Sicilian patients with Hb
      S/beta-thalassemia.
AB  - Although, several reports have detailed that hydroxyurea can ameliorate the
      clinical course of adult and pediatric patients with sickle cell anemia (Hb S or
      beta(S)), few clinical studies have been carried out in patients with
      beta(S)/beta-thalassemia. In a two-year clinical study, we evaluated the efficacy
      of hydroxyurea in a group of 22 adult Sicilian patients with beta(S)/beta
      thalassemia with severe phenotypes. Among the 20 patients evaluated during 2
      years of treatment, we observed a very good clinical response with a 93%
      reduction of the annual number of crises (median 7 versus 0.5 crises per year; P
      < 0.001) and of days in hospital (mean 22+/- 21.9 versus 1.2 +/- 2.3; P < 0.001),
      a significant increase in Hb F (7.5 +/- 5.3% versus 25.2 +/- 5.2%; P < 0.001) and
      in MCV (73.1 +/- 4.8 fL versus 96.4 +/- 7.2 fL; P < 0.001), and no significant
      modifications in Hb (9.6 +/- 1.3 g/dL versus 10.0 +/- 1.5 g/dL; P > 0.05) and in
      WBC (11.4 +/- 3.9 x 10(9)/L versus 10.2 +/- 3.9 x 10(9)/L; P > 0.05). Twelve
      patients had no crises from the first month of treatment; 16 patients showed a 2
      3-fold increase over baseline in Hb F. During the study no severe complications
      and no important side effects of hydroxyurea were observed. Our data suggest that
      hydroxyurea efficacy in patients with beta(S)/beta-thalassemial may be greater
      than that described in patients with sickle cell disease. This pattern and
      durability of response will need to be confirmed in a larger, randomized,
      clinical trial.

PMID- 11300354
TI  - Thalassemia intermedia and extramedullary hematopoiesis associated with compound
      heterozygosity for the 532 bp deletion of the beta-globin gene and gene deletion
      hereditary persistence of fetal hemoglobin.

PMID- 11300355
TI  - Hb Yaounde [beta134(H12)Val-->Ala], a new neutral variant found in association
      with Hb Kenitra.

PMID- 11300356
TI  - Myocardial protection during acute myocardial infarction: the need for a simple
      large randomized trial with GIK.

PMID- 11300357
TI  - Role of beta-adrenergic receptor subtypes in lipolysis.
AB  - In vitro lipolysis stimulated by low (-)-isoprenaline concentrations (< or =30
      nM) in epididymal white adipocytes from Sprague-Dawley rats was inhibited at
      least 60-80% by the specific beta1-antagonists LK 204-545 and CGP 20712A (1
      microM), suggesting that at these low (10 nM) concentrations of (-)-isoprenaline
      lipolysis was primarily (80%) but not solely mediated via beta1-adrenergic
      receptors. Low concentrations (100 nM) of (-)-noradrenaline and formoterol also
      confirmed a role for beta1-adrenergic receptors in mediating lipolysis at low
      concentrations of these agonists. At higher agonist concentrations, beta3
      adrenergic receptors were fully activated and were the dominant beta-adrenergic
      receptor subtype mediating the maximum lipolytic response, and the maximum
      response was not affected by the beta1-antagonists, demonstrating that the beta3
      receptor is capable of inducing maximum lipolysis on its own. Studies of
      lipolysis induced by the relatively beta2-selective agonist formoterol in the
      presence of beta1-blockade (1 microM CGP 20712A) demonstrated the inability of
      the beta2-selective antagonist ICI 118-551 to inhibit the residual lipolysis at
      concentrations of ICI 118-551 < or = 1 microM. Higher concentrations of ICI 118
      551 inhibited the residual formoterol-induced lipolysis competetively, but with
      low affinity (approximately 500-fold lower than its beta2-adrenergic receptor
      pA2, 7.80 +/- 0.21), suggesting that formoterol was not acting via beta2
      adrenergic receptors. These data are consistent with beta1-adrenergic receptors
      playing an important role in lipolysis at physiological but not pharmacological
      concentrations of catecholamines and that beta2-adrenergic receptors play no
      obvious direct role in mediating beta-adrenergic receptor agonist-induced
      lipolysis in vitro. Finally, racemic-SR 59230A, unlike the pure (S, S)-isomer (a
      beta3-selective antagonist), was found to be a nonselective antagonist at the
      three beta-adrenergic receptor subtypes, showing that the other enantiomers have
      different selectivity.

PMID- 11300358
TI  - Endothelin-A receptor antagonism during acute myocardial infarction in rats.
AB  - Endothelin levels are increased in rats with experimentally induced myocardial
      infarction. The purpose of this study was to determine whether endothelin-A
      (ET(A)) receptor antagonism alters ventricular remodeling and the development of
      heart failure after myocardial infarction (MI). We administered 10 mg/kg/day of A
      127722 to rats post-MI for 6 weeks. A hemodynamic study was performed and passive
      pressure-volume curves obtained. In rats without infarcts, ET(A) receptor
      antagonist (n = 8; vehicle, n = 5) had no effect. However, in rats with infarcts
      ET(A) antagonism (n=14, MI = 35%; vehicle: n = 19, MI = 32%) reduced systemic
      arterial and LV systolic (but not end-diastolic) pressures and shifted the
      pressure-volume relationship to the right. Because LV mass was not changed, the
      volume-to-mass ratio was increased and was correlated inversely with the ability
      of the LV to maximally develop pressure. This increase in volume at low
      distending pressures was also coupled with a tendency (P < 0.06) for reduced scar
      thickness, suggesting that early initiation of an ET(A) receptor antagonism
      increased infarct expansion. The reduction in blood pressure offset the increase
      in volume such that wall stresses were unchanged, as was LV mass. The early use
      of ET(A) receptor antagonism in the rat model of myocardial infarction did not
      beneficially alter LV remodeling.

PMID- 11300359
TI  - Long-term mortality after acute myocardial infarction in relation to prescribed
      dosages of a beta-blocker at hospital discharge.
AB  - This study was designed to describe the 5-year mortality rate in relation to the
      dose of metoprolol prescribed at hospital discharge after hospitalisation for
      acute myocardial infarction (AMI). All patients discharged alive after being
      hospitalized for AMI at Sahlgrenska Hospital (covering half of the community of
      Goteborg, with 500,000 inhabitants) during 1986-1987 (period I) and all patients
      discharged alive after hospitalization for AMI at Sahlgrenska Hospital and Ostra
      Hospital (covering the whole area of the community of Goteborg) in 1990-1991
      (period II) were included. Overall mortality was retrospectively evaluated over 5
      years of follow-up. In all there were 2161 patients who were discharged after
      AMI. Seventy-three percent of these patients were prescribed a beta-blocker and
      59% were prescribed metoprolol. Of the patients prescribed metoprolol, 34% were
      on 200 mg, 46% on 100 mg, and 20% on 50 mg or less. Information on 5-year
      mortality was available for 2142 of the 2161 patients (99.1%). The 5-year
      mortality was 24% among patients prescribed 200 mg, 33% among patients prescribed
      100 mg, and 43% among patients prescribed 50 mg (P < 0.0001). Patients prescribed
      another beta-blocker had a 5-year mortality of 39%, and patients prescribed no
      beta-blocker at all had a 5-year mortality of 61%. When correcting for
      dissimilarities at baseline, patients who were prescribed < or =100 mg had an
      adjusted risk ratio for death of 0.79 (95% confidence limit 0.64-0.96; P = 0.021)
      as compared with patients not prescribed a beta blocker. The corresponding figure
      for patients prescribed >100 mg was 0.63 (95% confidence limit 0.48-0.84; P =
      0.001). Both patients prescribed high and low doses of metoprolol after AMI
      appeared to benefit from treatment. There was a trend indicating more benefit
      when larger doses were prescribed.

PMID- 11300360
TI  - Combined treatment with ramipril and metoprolol prevents changes in the creatine
      kinase isoenzyme system and improves hemodynamic function in rat hearts after
      myocardial infarction.
AB  - Beneficial effects of monotherapy with ACE inhibitors or beta-blockers on
      hemodynamic function after myocardial infarction are well known. Until now, the
      effects of combined treatment on cardiac function and energy metabolism have been
      poorly described. This study examines the effects of combined ramipril and
      metoprolol treatment on the creatine kinase (CK) system and hemodynamic function
      in rats after infarction. Wistar rats with experimental infarction were
      randomized for treatment with ramipril (R), metoprolol (M), combined treatment
      (MR), or placebo (P). Sham-operated (SO) animals served as controls. After 6
      weeks, we assayed for CK isoenzymes and performed hemodynamic measurements. In P
      versus SO, left ventricular systolic pressures (dp/dt(max) and dp/dt(min))
      diminished, whereas left ventricular end-diastolic pressure (LVEDP) increased.
      Decreased total CK activity and mitochondrial CK isoenzyme, increased CK-MB, and
      increased CK-BB isoenzymes were measured in P versus SO. With infarct size < or
      =45%, mitochondrial CK increased in M and R versus P. Combined treatment had an
      additional enhancing effect on mitochondrial CK isoenzyme level versus M and R,
      decreased LVEDP versus P, as well as increased dp/dt(max) and dp/dt(min) versus
      R. These results provide evidence of an interaction between normalization of
      energy metabolism and improvement in cardiac function due to a combination of ACE
      inhibition and beta blockade after myocardial infarction.

PMID- 11300361
TI  - Adenosine A1 agonist at reperfusion trial (AART): results of a three-center,
      blinded, randomized, controlled experimental infarct study.
AB  - Adenosine A1 receptor agonists given prior to myocardial ischemia limit ischemic
      injury in several species. However, the ability of adenosine receptor agonists to
      limit infarct size when given at reperfusion has proved controversial. We
      designed a three-center experimental study using a blinded, randomized treatment
      protocol to test the hypothesis that adenosine A1 receptor activation during
      early reperfusion can attenuate lethal reperfusion injury, thereby reducing
      infarct size. Sixty anesthetized rabbits (20 in each laboratory) underwent 30
      minutes coronary artery occlusion followed by 120 minutes reperfusion. The
      selective adenosine A1 receptor agonist GR79236 (10.5 microg/kg, a dose shown to
      limit infarction in this model when given before ischemia) or vehicle were
      administered IV 10 minutes before reperfusion. Infarct size was assessed by
      tetrazolium staining and, after the randomization code was revealed, data from
      the three laboratories were pooled for statistical analysis. Infarct size was not
      modified by administration of GR79236. In the vehicle-treated group, the infarct
      to-risk ratio was 28.9 +/- 2.7% (n = 24) compared with 31.9 +/- 2.6% (n = 26) in
      the GR79236-treated group (not significant). Risk zone volume was similar in the
      two groups (1.06 +/- 0.05 cm3 vs 1.00 +/- 0.05 cm3, respectively). A modest
      reduction in rate-pressure product was noted following the administration of
      GR79236, but this effect was transient. The same dose of GR79236 was found to
      limit infarct size when given prior to coronary artery occlusion. We conclude
      that A1 receptor activation does not modify lethal reperfusion injury in
      myocardium.

PMID- 11300362
TI  - Glucose-insulin-potassium reduces infarct size when administered during
      reperfusion.
AB  - Coronary reperfusion improves ventricular function and survival after infarction,
      but the metabolic conditions at this time may not be optimal to protect the
      heart. The objective of this study was to evaluate if metabolic support with
      glucose-insulin-potassium (GIK) administered at the time of coronary reperfusion
      could elicit the same cardioprotection as GIK infusion during the entire
      ischemia/reperfusion period. Three groups of anesthetized, open-chest rats were
      subjected to 30 minutes of regional ischemia and 180 minutes of reperfusion.
      Groups 1 (controls) and 2 (GIK(IR)) received saline or GIK, respectively,
      throughout the whole experimental period, whereas a third group (GIK(R)) received
      GIK from the onset of reperfusion only. Infarct size was significantly reduced in
      the GIK-treated groups, compared with controls (GIK(IR) 44 +/- 5% and GIK(R) 45
      +/- 5% vs. control 66 +/- 4%; P < 0.05). Postischemic recovery of cardiac
      function improved when GIK was only administered during the reperfusion phase.
      Furthermore, infusion of GIK resulted in reduced plasma concentrations of free
      fatty acids and increased plasma glucose (both P < 0.05) compared with controls.
      This study demonstrates that glucose-insulin-potassium administration at the
      onset of the postischemic reperfusion period is as cardioprotective as
      administration of GIK during the entire ischemia/reperfusion period.

PMID- 11300363
TI  - Effects of magnesium and its mechanism on the incidence of reperfusion
      arrhythmias following severe ischemia in isolated rat hearts.
AB  - Magnesium sulfate (Mg) has been widely used for the treatment of ventricular
      arrhythmias (VF) in patients with coronary artery disease. However, the
      mechanisms of prevention on the incidence of VF have not been defined. The aim of
      study was to investigate the role of Mg in the prevention of VF and the mechanism
      of those effects. Series 1 studied antiarrhythmic effects on VF. Isolated rat
      hearts were perfused in the working heart mode with Krebs'-Henseleit bicarbonate
      buffer (KHB). Whole heart ischemia was induced by a one-way ball valve with 300
      beats/min electrical pacing for 10 minutes followed by 20 minutes of aerobic
      reperfusion. After control perfusion, Mg was added from 5 minutes before ischemia
      and was continued to the end of ischemia (1.2 mM for the control group and 2.4,
      3.6, 4.8, and 9.6 mM for the study animals) or during reperfusion (3.6 mM). Left
      ventricular pressure, aortic flow, and ECG were monitored. Series 2 studied the
      effect of Mg on [Ca2+]i. Hearts were perfused by the Langendorff mode and were
      loaded with 4 microM of Fura 2/AM as a [Ca2+]i indicator. Ca2+ was monitored
      using the ratio of Fura-2 fluorescence intensity at excitation wavelengths of 340
      and 380 nm. The hearts were subjected to a 20 minutes of low-flow ischemia
      followed by 20 minutes of aerobic reperfusion. Then 3.6 mM Mg was added to the
      KHB medium during ischemia. The duration of VF was significantly suppressed in
      the 2.4, 3.6, and 4.8 mM/L Mg-added groups (472 +/- 173, 779 +/- 159, and 525 +/-
      202 second, respectively) when compared with the control group (1200 seconds).
      Magnesium sulfate suppressed the fluorescence ratio of the diastolic Ca2+ level
      at the end of 20 minutes of ischemia from 40.5 +/- 3.6% to 9.0 +/- 1.0% (P < 0.05
      vs. control hearts). These results suggested that Mg had a beneficial effect on
      VF and that the optimal Mg concentration was between 2.4 and 4.8 mM. The
      mechanism of the prevention of VF by Mg could be through the inhibition of
      [Ca2+]i retention during ischemia.

PMID- 11300364
TI  - Early experience with intravascular ultrasound in evaluating the effect of
      statins on femoropopliteal arterial disease: hypothesis-generating observations
      in humans.
AB  - The purpose of this study was to compare the vascular response seen with
      intravascular ultrasound (IVUS) at 1-year follow-up between statin-treated and
      non-statin-treated patients. Patients (n = 10) undergoing percutaneous
      transluminal angioplasty (PTA) of the femoropopliteal artery were studied with
      IVUS immediately after PTA and at 1-year follow-up. In nondilated matched
      vascular segments, the change in lumen, vessel, and plaque volume was assessed.
      In balloon-dilated matched vascular segments, the change in lumen, vessel, and
      plaque area was assessed. A comparison was made between statintreated (n = 5) and
      non-statin-treated patients (n = 5) in lumen, vessel, and plaque changes. At
      follow-up, both statin-treated and non-statin-treated patients showed a similar
      increase in plaque volume at the nondilated segment (+4% and +2%, respectively).
      In statin-treated patients the plaque volume increase was compensated by an
      increase in vessel volume (+2%), resulting in an increase in lumen volume (+1%).
      In non-statin-treated patients, on the other hand, the increase in plaque volume
      was associated with a decrease in vessel volume (-2%), resulting in a decrease in
      lumen volume (-4%). At the balloon-dilated segment a similar trend in changes of
      lumen, vessel, and plaque was encountered. Differences between both groups of
      patients were not statistically significant. Despite the nonsignificant nature of
      the observation, this small retrospective IVUS study may generate the hypothesis
      that statin therapy may contribute to superior long-term lumen dimensions by
      inducing positive vascular remodeling both in nondilated and balloon-dilated
      vascular segments.

PMID- 11300365
TI  - Comparison of the effect of verapamil and propranolol on response of coronary
      vasomotion to cold pressor test in symptomatic patients with hypertrophic
      cardiomyopathy.
AB  - Impaired endothelium-dependent vasodilatation of coronary resistance vessels has
      been demonstrated in patients with hypertrophic cardiomyopathy (HC). The aim of
      this study was to compare the effect of verapamil and propranolol on the response
      of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance
      index to the cold pressor test (CPT) in symptomatic HC patients. In 15 patients
      with HC, the CBFV was measured in the distal portion of the left anterior
      descending coronary artery using high-sensitivity transthoracic Doppler
      echocardiography. Peak diastolic CBFV and coronary vascular resistance index
      (calculated as ratio of mean aortic pressure/CBFV ratio) were measured at
      baseline and after CPT. Changes of these parameters induced by the CPT (expressed
      as percentage of baseline values) were compared after verapamil and propranolol
      treatment in a crossover study. The same measurements were obtained in nine
      healthy control subjects. CPT induced an increasing pattern of CBFV during
      verapamil therapy, which was absent in CPT after propranolol administration (10.1
      +/- 5.6% vs. -0.9 +/- 4.1%, P < 0.01). In healthy controls CBFV increased in
      response to CPT more than in HC patients receiving verapamil or propranolol
      (23.1+/- 12.8% P < 0.01 and P < 0.05, respectively). The coronary vascular
      resistance index increased during the CPT significantly less on verapamil than on
      propranolol treatment (3.5 +/- 9.2% vs. 18.1 +/- 13.5%, P < 0.01). In healthy
      controls the coronary vascular resistance index decreased during CPT -4.5 +/-
      8.5% (P < 0.05 vs. verapamil and P < 0.01 vs. propranolol). Verapamil improved
      the coronary vasomotor response to CPT in relation to propranolol. Verapamil
      blunted the increase of the coronary vascular resistance index to the CPT in
      comparison with its change at CPT after propranolol. Thus, coronary endothelial
      dysfunction in symptomatic HC patients may be partially reduced by verapamil in
      comparison with propranolol treatment.

PMID- 11300366
TI  - Dose-dependent effects of intracoronary verapamil on systemic and coronary
      hemodynamics.
AB  - Calcium antagonists are used in interventional cardiology to prevent coronary
      vasoconstriction or to overcome the no-reflow phenomenon. The aim of the current
      study was to evaluate the dose-dependent effects of intracoronary verapamil on
      systemic and coronary hemodynamics. In 20 patients scheduled for routine coronary
      angiography, heart rate, blood pressure, and ECG recordings were recorded
      continuously and intracoronary flow velocity was obtained by intracoronary
      Doppler measurements in angiographically normal vessels. The cross-sectional
      area, measured by quantitative coronary angiography, allowed the calculation of
      coronary blood flow (CBF) and the coronary vascular resistance index (CVRI).
      Without premedication, increasing dosages of verapamil (0.01 mg, 0.1 mg, 1.0 mg,
      and 2.0 mg) were injected into the left coronary artery. Intracoronary verapamil
      administration led to a decrease in systemic blood pressure only after
      administration of 1.0 mg or 2.0 mg (change in mean arterial pressure: from 87.6
      +/-14.6 mmHg to 80.1 +/- 14.9 mmHg and 78.5 +/- 13.9 mmHg, respectively; both P <
      0.05) without a change in heart rate. Epicardial diameters of the left coronary
      artery increased only at dosages of 1.0 mg and 2.0 mg (from 2.14 +/- 0.4 mm to
      2.22 +/- 0.3 mm, P < 0.01), whereas the coronary blood flow velocity increased
      significantly at the smallest dosage of 0.01 mg (from 19.9 +/- 8.7 cm/s to 33.2
      +/- 14.9 cm/s, P < 0.001) and was further enhanced with increasing dosages. CBF
      increased and CVRI decreased at every dosage of verapamil compared with baseline
      values. CBF increased also after 0.1 mg (from 13.5 +/- 6.5 mL/min to 19.5 +/- 9.3
      mL/min; P < 0.05), reaching a maximal effect after administration of 1.0 mg
      verapamil (26.3 +/- 16.1 mL/min, P < 0.05). Application of 2.0 mg did not further
      increase CBF compared with 1.0 mg. Intracoronary application of verapamil leads
      to a decrease in systemic blood pressure at higher dosages, whereas heart rate
      remains unchanged at any dosage. The maximal increase in coronary blood flow and
      decrease in vascular resistance can be reached by administration of 1.0 mg
      verapamil into the left coronary artery.

PMID- 11300367
TI  - Quinaprilat-induced vasodilatation in forearm vasculature of patients with
      essential hypertension: comparison with enalaprilat.
AB  - The aim of the present study was to assess the possible differences in
      hemodynamic and neurohumoral responses to local ACE inhibition in the human
      forearm of patients with essential hypertension with either quinaprilat or
      enalaprilat. Forearm vascular responses to infusion of quinaprilat or enalaprilat
      (0.5 microg/dL/min) into the brachial artery were studied in 12 male patients
      with essential hypertension. The experiments were performed in a randomized,
      double-blind, crossover fashion. Before and during ACE inhibition, the
      vasoconstrictor response to four cumulative doses of angiotensin I (Ang I) was
      studied. Forearm blood flow was assessed using venous occlusion plethysmography.
      Local quinaprilat infusion induced a more rapid (even after 15 minutes; median
      vasodilation quinaprilat 29% vs. enalaprilat --1%, P < 0.02) and longer lasting
      forearm vasodilation as compared with enalaprilat. After 15 minutes of local ACE
      inhibition, the vasoconstrictor response to Ang I was completely blocked by both
      ACE inhibitors. We conclude that in patients with essential hypertension
      quinaprilat induces a more rapid and longer lasting vasodilatation than
      enalaprilat. These effects of quinaprilat are possibly related to its higher
      affinity for vascular ACE. On the other hand, the fact that these effects of
      quinaprilat were observed despite a similar degree of ACE inhibition as during
      enalaprilat may suggest that quinaprilat directly stimulates another
      vasodilatating mechanism.

PMID- 11300368
TI  - Hypoglycemic effect of cibenzoline in patients with abnormal glucose tolerance
      and frequent ventricular arrhythmias.
AB  - While some antiarrhythmic agents have potential hypoglycemic effects and indeed
      some reports of hypoglycemic adverse effect of those drugs, no systematic reports
      have been issued. We studied the hypoglycemic effects of cibenzoline, a class I
      antiarrhythmic agent. Cibenzoline succinate (150-300 mg/day) was given orally for
      12 weeks to 10 patients who had ventricular premature complexes (VPCs) of >1000
      per 24 hours and abnormal glucose tolerance before treatment with cibenzoline.
      Abnormal glucose tolerance, judged by a 75-g oral glucose tolerance test (OGTT),
      was defined as the response designated as "diabetic" or "borderline" type
      according to the criteria specified by the Japan Diabetes Society. In OGTT, the
      insulinogenic index (defined as the ratio of the increment of IRI [immunoreactive
      insulin] to that of plasma glucose at 30 minutes after a glucose load) and the
      sum of IRI (sigma IRI) were also determined. Holter ECG recordings, OGTT, and
      measurements of fasting plasma glucose IRI, and HbA(1c) were performed before and
      during cibenzoline treatment. Cibenzoline caused VPC reduction of >70% in 6 of
      the 10 patients. The drug significantly decreased fasting plasma glucose and
      HbA(1c) (mean +/- SD) 12 weeks after treatment, from 6.18 +/-0.92 mM/L to 5.54 +/
      1.08 mM/L and from 6.17 +/- 1.03% to 5.83 +/- 0.96%, respectively (P < 0.05).
      While it significantly increased fasting IRI from 4.99 +/- 1.50 to 6.51 +/- 1.47
      microU/mL (P < 0.01), the insulinogenic index from 0.33 +/- 0.26 to 0.65 +/- 0.38
      (P < 0.05), and sigma IRI from 168 +/- 67 microU/mL to 199 +/-46 (P < 0.05).
      Cibenzoline exerted a hypoglycemic effect, facilitating insulin secretion in
      patients with abnormal glucose tolerance and ventricular arrhythmias.

PMID- 11300369
TI  - PREAMI: Perindopril and Remodelling in Elderly with Acute Myocardial Infarction:
      study rationale and design.
AB  - Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, the development
      of remodeling, left ventricular (LV) dysfunction, and ischemic events, both when
      administered alone as long-term treatment in patients with impaired LV function
      and/or heart failure (HF) and as short-term treatment, early after acute
      myocardial infarction (AMI) and/or HF. The few data available on the use of ACE
      inhibitors in the elderly after AMI are conflicting. Nothing is known about the
      effects of ACE inhibitors in elderly postinfarction patients with preserved LV
      function: these patients have a remarkable medium- to long-term mortality and HF
      incidence after infarction. The aim of this study is to evaluate, in patients
      with AMI aged > or =65 years, the effects of Perindopril on the combined outcome
      of death, hospitalization for HF, and heart remodeling, considered to be a > or
      =8% increase in LV end-diastolic volume (LVEDV). Secondary objectives include the
      same factors listed in the primary end points but considered separately. In
      addition, safety of the drug, ventricular remodeling, and adaptation are being
      evaluated. A total of 1100 patients with AMI (first episode or reinfarction),
      aged > or =65 years, and preserved or only moderately depressed LV (LV ejection
      fraction > or =40%), are to be enrolled and randomly assigned to treatment (8 mg
      for 12 months of Perindopril or placebo, in double-blind conditions). Clinical
      assessment is performed at fixed times, and periodic evaluations of (1)
      ventricular shape, dimensions, and function by quantitative 2-D echocardiography,
      and (2) heart rate variability and arrhythmias by ambulatory electrocardiographic
      monitoring are anticipated. The results and conclusions will be available by 2002
      year.

PMID- 11300370
TI  - Drug interactions with colesevelam hydrochloride, a novel, potent lipid-lowering
      agent.
AB  - Colesevelam hydrochloride (colesevelam) is a novel, potent, bile acid-binding
      agent that has been shown to lower LDL cholesterol a mean of 19% at a dose of 3.8
      g/d. We studied the pharmacokinetics of colesevelam coadministered with six
      drugs: digoxin and warfarin, agents with narrow therapeutic indices; sustained
      release verapamil and metoprolol; quinidine, an antiarrhythmic with a narrow
      therapeutic index; and valproic acid, an antiseizure medication. Six individual
      studies were single-dose, crossover, with or without a 4.5-g dose of colesevelam.
      Plasma levels were determined using validated analytical methods. Values for the
      ratio of ln[AUC(0-t)] with and without colesevelam were 107% for quinidine, 102%
      for valproic acid, 89% for digoxin, 102% for warfarin, 82% for verapamil, and
      112% for metoprolol. Values for the ratio of ln[Cmax] with and without
      colesevelam were 107% for quinidine, 92% for valproic acid, 96% for digoxin, 99%
      for warfarin, 69% for verapamil, and 112% for metoprolol. The 90% confidence
      intervals for these ratios and for values of ln[AUC(0-inf)] that could be
      determined were within the 80-125% range, with the exception of verapamil. In
      this study, verapamil had great interindividual variability, with a 28-fold range
      in Cmax and an 11-fold range in AUC(0-t). In summary, pharmacokinetic studies
      with colesevelam did not show clinically significant effects on absorption of six
      other coadministered drugs.

PMID- 11300371
TI  - Calcium-dependent vasorelaxant capacity of levosimendan in porcine and human
      epicardial coronary artery preparations.

PMID- 11300372
TI  - Intravascular radiation and stenting: absence of efficacy on intimal
      proliferation in a rabbit model.

PMID- 11300373
TI  - Statin therapy and plasma C-reactive protein levels in primary prevention.

PMID- 11300374
TI  - Aspirin therapy: need to develop individulized approach.

PMID- 11300375
TI  - The Lund concept for treatment of head injuries--faith or science?

PMID- 11300376
TI  - An outcome study of severe traumatic head injury using the "Lund therapy" with
      low-dose prostacyclin.
AB  - BACKGROUND: There are two independent head injury outcome studies using the "Lund
      concept", and both showed a mortality rate of about 10%, and a favourable outcome
      (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at
      controlling intracranial pressure, and improving microcirculation around
      contusions. Intracranial pressure is controlled by maintaining a normal colloid
      osmotic pressure and reducing the hydrostatic capillary pressure.
      Microcirculation is improved by ensuring strict normovolaemia and reducing
      sympathetic discharge. The endogenous substance prostacyclin with its
      antiaggregatory/antiadhesive effects may further improve microcirculation, which
      finds support from a microdialysis-based clinical study and an experimental brain
      trauma study. The present clinical outcome study aims at evaluating whether the
      previously obtained good outcome with the Lund therapy can be reproduced, and
      whether the addition of prostacyclin has any adverse side-effects. METHODS: All
      31 consecutive patients with severe head injury, Glasgow coma scale (GCS) < or =
      8, admitted to the University Hospital of Umea during 1998 were included. The
      Lund therapy including prostacyclin infusion for the first three days at a dose
      of 0.5 ng kg(-1) min(-1). Outcome was evaluated according to the GOS >10 months
      after the injury. RESULTS: One patient died, another suffered vegetative state
      and 7 severe disability. Of the 22 patients with favourable outcome, 19 showed
      good recovery and 3 moderate disability. No adverse side-effects of prostacyclin
      were observed. CONCLUSION: The outcome results from previous studies using the
      Lund therapy were reproduced, and no adverse side-effects of low-dose
      prostacyclin were observed.

PMID- 11300377
TI  - Cardiopulmonary bypass elicits a pro- and anti-inflammatory cytokine response and
      impaired neutrophil chemotaxis in neonatal pigs.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response
      and organ dysfunction, especially in children. Plasma concentration of
      inflammatory markers are increased in response to the trauma of cardiac surgery
      and CPB. The aim of the present study was to investigate whether the CPB
      procedure in itself elicits increased levels of inflammatory markers in neonatal
      pigs. METHODS: The inflammatory response was measured in piglets undergoing
      sternotomy alone (sham group, n=13) or sternotomy and CPB (n=14). Inflammatory
      mediators were measured at baseline and at fixed time-points during and after
      CPB. IL-8, IL-10 and TNF-alpha levels and C-reactive protein (CRP) concentrations
      were measured in plasma samples. Polymorphonuclear neutrophils (PMN) chemotaxis
      was measured ex vivo, and CD-18 expression using an immunofluorescence technique.
      RESULTS: Immediately after the CPB procedure increased IL-8 levels were found in
      the CPB group, but not in sham operated animals (P=0.005). Simultaneously, a
      marked IL-10 response was measured in the CPB group. Concurrently, PMN chemotaxis
      decreased in CPB animals but not in the sham group (P=0.04). CD-18 expression and
      CRP levels were not significantly different between groups and TNF-alpha showed
      no changes in either group. The chemotactic response did not correlate with
      plasma IL-8 or IL-10, nor with CD-18 expression. CONCLUSION: The CPB procedure
      elicited a systemic inflammatory response in terms of significantly elevated
      plasma levels of IL-8 and IL-10. Furthermore, a temporary and simultaneous
      decrease in PMN chemotaxis was observed immediately after CPB.

PMID- 11300378
TI  - Changes in circulating blood volume after infusion of hydroxyethyl starch 6% in
      critically ill patients.
AB  - BACKGROUND: The cardiovascular response to a volume challenge with hydroxyethyl
      starch (HES) (200/0.5) 6% depends on the relation between the volume of HES 6%
      infused and the expansion of the blood volume in critically ill patients.
      However, only relatively limited data exist on the plasma expanding effect of
      infusion of HES 6% in critically ill patients. The purpose of the study was to
      evaluate the variation in the expansion of the circulating blood volume (CBV) in
      critically ill patients after infusion of 500 ml of colloid (HES (200/0.5) 6%)
      using the carbon monoxide method. METHODS: In 20 consecutive patients admitted to
      the ICU requiring mechanical ventilation and volume expansion, 500 ml of HES
      (200/0.5) 6% was infused. The CBV was measured immediately before the infusion,
      10 min after completing the infusion and then hourly for 8 h. RESULTS: The median
      volume expansion immediately after infusion was 470 ml (range 270 ml to 840 ml).
      The corresponding values after 4 h and 8 h were 265 ml (range -30 ml to 460 ml)
      and 120 ml (range -210 ml to 360 ml), respectively. The increase in CBV was only
      statistically significant for 4 h. The coefficient of variation of the method for
      estimation of CBV was 3.6%. CONCLUSIONS: The large interindividual variation of
      the volume expansion after infusion of HES 6% in critically ill patients
      illustrates one of the difficulties in optimizing colloid therapy and
      interpretating the changes in hemodynamic variables after a colloid challenge.

PMID- 11300379
TI  - Effects of dopamine on porcine myocardial action potentials and contractions at
      37 degrees C and 32 degrees C.
AB  - BACKGROUND: Little information exists on the effects of drugs with cardiovascular
      action in hypothermia, and some findings have indicated paradoxic effects of
      dopamine in this setting. As we have not found any data on the electrophysiologic
      and contractile effects of dopamine on the heart in hypothermia, we decided to
      study this in pig myocardium, since pigs have a cardiovascular system more
      similar to that of humans than other animals. METHODS: Excised muscle strips from
      pig ventricular septum were mounted in an organ bath. After 45 min of
      equilibration at 37 degrees C or 32 degrees C, resting and action potentials,
      time to peak contraction and contractile force were recorded during pacing with a
      frequency of 60/min. Dopamine at 4 microM or 8 microM was added and new
      recordings were made after 15 min. RESULTS: Cooling to 32 degrees C caused a
      prolongation of contraction by 48% and the contractile force increased by 39%.
      The membrane action potential duration at 50% and 90% repolarization levels
      increased at 32 degrees C by 28% and 16% respectively. Dopamine significantly
      (P<0.05) increased the contractile force and membrane action potential duration
      at 50% and 90% repolarization levels both in normothermia and in hypothermia,
      whereas the duration of the contraction was not significantly changed.
      CONCLUSION: Cooling to 32 degrees C significantly prolongs the myocardial action
      potential and the contraction duration. Dopamine increases the contractile force
      and prolongs the action potential both at 37 degrees C and at 32 degrees C.

PMID- 11300380
TI  - Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal
      acidosis and systemic inflammatory responses following hypothermic
      cardiopulmonary bypass.
AB  - BACKGROUND: Phosphodiesterase (PDE) III inhibitors have both an inotropic and a
      peripheral vasodilatory effect, and also inhibit the activation of macrophages.
      Thus a newly developed PDE III inhibitor, olprinone, could modify gastric
      intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory
      responses in patients undergoing cardiac surgery with cardiopulmonary bypass
      (CPB). METHODS: We studied 23 patients. In 15 patients, olprinone (0.1 or 0.2
      microg x kg(-1) x min(-1)) was administered from the commencement of CPB until
      their admission to the ICU. The other 8 patients received placebo. The pHi and
      regional CO2 tension (PrCO2) were assessed by a capnometric air tonometry.
      Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6), IL
      10, and leucocyte counts. RESULTS: The pHi and PCO2-gap, the difference between
      PrCO2 and arterial CO2 tension (PaCO2), showed a transient decrease and an
      increase after CPB, respectively. Although olprinone did not affect pHi,
      olprinone at 0.2 microg x kg(-1) x min(-1) significantly lessened post-CPB
      increase in PCO2-gap. Olprinone at 0.2 microg x kg(-1) x min(-1) significantly
      increased IL-10 and reduced the extent of leucocytosis, while it did not affect
      IL-6 levels. At the same dosage, olprinone also lessened the surge in systemic
      oxygen uptake index (VO2) and augmented the increase in mixed oxygen saturation
      (SvO2) both of which occurred after CPB. At 0.1 microg x kg(-1) x min(-1),
      however, olprinone did not show any significant effect. CONCLUSION: Our results
      suggest that olprinone at 0.2 microg x kg(-1) x min(-1) suppresses gastric
      intramucosal acidosis and systemic inflammation following CPB.

PMID- 11300381
TI  - Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary
      hypertension and bronchoconstriction in dogs.
AB  - BACKGROUND: Magnesium (Mg2+) has relaxant effects on histamine-induced
      bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular
      smooth muscle tone and be clinically useful for treatment of persistent pulmonary
      hypertension of the newborn. In this study, we evaluated the relaxant effect of
      Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension.
      METHODS: Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1)
      + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)).
      Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg
      x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in
      bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by
      a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension
      was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR
      were expressed as per cent of the basal level. Thirty minutes after start of 5HT
      infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x
      kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level
      of Mg2+ and catecholamines. RESULTS: 5HT increased %PVR to 163+/-25% and
      decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000
      micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose
      producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and
      1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction,
      respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol
      x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x
      kg(-1) i.v.. CONCLUSION: In dogs, 5HT-induced pulmonary hypertension but not
      bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting
      in a plasma concentration within the assumed therapeutic level.

PMID- 11300382
TI  - No effect of L-arginine supplementation on pulmonary endothelial dysfunction
      after cardiopulmonary bypass.
AB  - BACKGROUND: Acetylcholine is an endothelium-dependent vasodilator through the L
      arginine-nitric oxide pathway. After ischemia-reperfusion this effect is
      attenuated, also demonstrated in the pulmonary circulation after cardiopulmonary
      bypass. Administration of L-arginine has been shown to have a protective effect
      on endothelial function in reperfusion injury. The aim of the current study was
      to test the possible effect of L-arginine on the acetylcholine reactivity in the
      pulmonary circulation after cardiopulmonary bypass. METHODS: Thirty-five patients
      with ischemic and/or valvular heart disease were investigated in a randomized,
      double-blinded, placebo-controlled study. The patients were divided into three
      groups. Group 1: high dose L-arginine (n=10), group 2: low dose L-arginine
      (n=10), group 3: placebo, no L-arginine, (n=15). The acetylcholine reactivity was
      tested with measurements of pulmonary vascular resistance before surgery and 1, 2
      and 3-4 h after cardiopulmonary bypass. RESULTS: After cardiopulmonary bypass an
      attenuation of the acetylcholine reactivity over time was observed in all groups,
      with no differences between groups. CONCLUSION: In the current study L-arginine
      had no protective effect on the pulmonary endothelium after cardiopulmonary
      bypass, measured as reactivity to an infusion of acetylcholine.

PMID- 11300383
TI  - Etomidate and thiopental inhibit platelet function in patients undergoing
      infrainguinal vascular surgery.
AB  - BACKGROUND: Postoperative platelet hyperaggregability following general
      anesthesia has been reported in patients undergoing major vascular surgery. In
      contrast, since anesthetic agents inhibited platelet function both in vitro and
      in vivo, an increased risk for postoperative bleedings due to prolonged platelet
      dysfunction has been discussed. Nevertheless, data describing platelet-affecting
      properties of induction agents such as etomidate and thiopental in patients
      undergoing major vascular surgery are lacking. METHODS: Platelet function was
      determined at 0, 2, 20, and 200 microg/ml thiopental and at 0, 0.2, 2, 20
      microg/ml etomidate in vitro in blood samples drawn from 16 patients suffering
      from severe occlusive arterial disease. In addition, 30 patients undergoing
      vascular surgery were investigated before (PRE) and after anesthesia induction
      (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14),
      and 2 h after the beginning of surgery (T2). Platelet function was determined
      according to platelet aggregation, in vitro bleeding time, and flow cytometric
      measurements. RESULTS: In vitro, P-selectin expression was inhibited by etomidate
      at 2 and 20 microg/ml (-28% and -38%, respectively) and also by thiopental at 200
      microg/ml (-27%). In patients undergoing vascular surgery, anesthesia induction
      in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and
      an inhibition of ADP- and collagen-induced platelet aggregation (-30% and -17%,
      respectively) and of P-selectin expression (-25%) at T0. In the THIO group, only
      ADP-induced platelet aggregation was affected (-16%). At T2, all parameters had
      reached PRE level again in both groups. Furthermore, in comparison with the THIO
      group, operation time was significantly prolonged and transfusion volume was
      significantly increased in the ETO group. In addition, platelet count and
      hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1,
      fibrinogen and antithrombin III and partial thromboplastin time remained
      unchanged in both groups during the study period. CONCLUSIONS: In the present
      study, etomidate and, to a minor extent, thiopental offered significant platelet
      inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher
      transfusion rates and prolonged operation times. Therefore, anesthetic-related
      platelet inhibitory properties should be considered when searching for the
      anesthetic agent of choice, especially in patients with compromised hemostasis
      and co-existing bleeding disorders.

PMID- 11300384
TI  - Price development in important anesthesia and critical care medicine journals in
      comparison to journals of other disciplines.
AB  - BACKGROUND: In today's climate of financial restrictions, libraries and
      individual subscribers complain about the price increase of scientific journals.
      The development in prices of anesthesia/critical care journals was analysed over
      the past 6 years and compared to prices of some journals of other disciplines.
      METHODS: Important journals in the categories Anesthesiology, Emergency Medicine
      & Critical Care, Surgery, Medicine (General), and Cardiac & Cardiovascular
      Systems listed in the 1999 Science Citation Index of Journal Citation Report were
      included and prices for the years 1995 to 2000 were analysed. RESULTS: Increase
      in prices ranged from +13% to +199%. The mean increase in journal prices was
      lowest in the category Anesthesiology (+61%), higher in the category Critical
      Care (+73%), and highest in the category Medicine, General (+101%). Changes in
      the impact factor (IF) varied widely, ranging from a decrease (Lancet: -43%; J
      Neurosurg Anesth: -44%) to a tremendous increase (e.g. Reg Anesth +165%; Ann
      Emerg Med +149%). The journals' size (number of articles or pages) did not
      increase proportionally with the increase in prices. CONCLUSION: A
      disproportionate rise in journal prices was seen over the past 6 years. The large
      increase in cost may have multiple reasons. The rapidly increasing cost of
      research journals may affect research quality because economic pressure may
      result in reduction in availibility of information due to cancellation of
      subscriptions to journals.

PMID- 11300385
TI  - Management of postoperative pain in Spain.
AB  - BACKGROUND: The management of postoperative pain is suboptimal world-wide. This
      survey was carried out to determine current management in Spanish hospitals.
      METHODS: Spanish hospitals were divided into two groups: <200 beds (n=346) and
      >200 beds (n=186). A structured questionnaire was mailed to the heads of the
      anaesthesiology services of a random sample of 150 of hospitals of <200 beds, and
      all larger hospitals. RESULTS: Only 19% of hospitals with <200 beds responded and
      further analysis of this group was not possible; 53% of hospitals with >200 beds
      responded. In this sample (>200 beds), 45% of patients receive information on
      postoperative pain, given by the anaesthesiologist in 78% of cases. Over 70% of
      the hospitals do not have an acute pain unit and responsibility for postoperative
      pain lies with the anaesthesiology team in 71%, with the surgical team in 40% and
      with nursing in 33%, with an overlap of pain caretakers. Pain is measured on the
      surgical wards in 36% and recorded with the vital signs in 34%. On post
      anaesthetic recovery wards, analgesia is most frequently given by intravenous
      (83%), epidural (78%) and continuous intravenous (66%) administration. On
      surgical wards, the most frequent routes that are available are epidural (72%),
      intravenous (69%) and intramuscular (58%). Only 28% of the anaesthesiology
      services are satisfied with the pain treatment carried out in their hospitals. No
      significant differences on postoperative pain management were observed between
      teaching and non-teaching institutions. CONCLUSION: The survey shows that the
      management of postoperative pain in hospitals with >200 beds in Spain is
      suboptimal and this is associated with dissatisfaction among many
      anaesthesiologists.

PMID- 11300386
TI  - Patient-controlled epidural analgesia versus continuous epidural analgesia after
      total knee arthroplasty.
AB  - BACKGROUND: Patient-controlled epidural analgesia (PCEA) has been found to be an
      effective method for pain relief during labour and after surgery. The goal of
      this study was to compare the efficacy of bupivacaine-fentanyl PCEA and
      continuous epidural infusion with the same mixture for treatment of pain after
      total knee arthroplasty. METHODS: Fifty-four patients under spinal anaesthesia
      were allocated to two groups in this randomized, double-blind study: the PCEA
      group could demand a bolus of 0.05 ml/kg of the bupivacaine 1.1 mg/ml and
      fentanyl 5 microg/ml solution, with a lockout interval of 10 min and total dose
      limit of three bolus doses per hour. The EPI group received a continuous infusion
      of 0.1 ml kg(-1) h(-1) of the same bupivacaine-fentanyl solution, and only a
      minimal extra bolus dose of 0.2 ml with the same lockout interval. All the
      patients received also paracetamol 1 g, orally, three times a day. In addition to
      pain scores at rest and during leg lifting, the 20-h analgesic consumption and
      the incidence of side effects were recorded. RESULTS: Forty-nine patients
      completed the study. The bupivacaine and fentanyl consumption during 20 h was
      smaller in the PCEA group (P<0.001). Analgesia and the need for rescue-opioid
      medication were similar in both groups. There were no differences between the
      PCEA and EPI groups regarding the incidence of side effects. Five patients were
      confused about how to operate the PCEA apparatus. CONCLUSION: The amount of
      bupivacaine-fentanyl solution consumed was significantly less with PCEA than with
      continuous infusion of bupivacaine-fentanyl solution without affecting the
      quality of postoperative analgesia after total knee arthroplasty. Several of the
      elderly patients had difficulties in operating the PCEA apparatus.

PMID- 11300387
TI  - Total knee replacement: a comparison of ropivacaine and bupivacaine in combined
      femoral and sciatic block.
AB  - BACKGROUND: Femoral and sciatic nerve block may improve post-operative analgesia
      following total knee replacement. OBJECTIVES: To compare the post-operative
      analgesia following primary total knee replacement provided by spinal anaesthesia
      alone or in combination with femoral and sciatic nerve block with bupivacaine or
      ropivacaine. METHODS: Seventy-five patients were randomised into one of three
      groups: spinal anaesthesia only; spinal anaesthesia and combined femoral and
      sciatic nerve block with 1 mg x kg(-1) bupivacaine 7.5 mg x ml(-1) to each nerve;
      spinal anaesthesia and combined femoral and sciatic nerve block with 1 mg x kg(
      1) ropivacaine 7.5 mg x ml(-1) to each nerve. RESULTS: The mean (SD) time to
      first morphine request was significantly prolonged for both groups receiving
      combined femoral and sciatic block, 912 (489) min for the bupivacaine group and
      781 (394) min for the ropivacaine group (P<0.001) compared with 413 (208) min for
      the group receiving spinal anaesthesia alone. Morphine consumption was
      significantly reduced in both groups receiving combined femoral and sciatic
      block. There were no systemic or neurological sequelae in any of the groups.
      CONCLUSIONS: Femoral and sciatic blockade following intrathecal
      bupivacaine/diamorphine provided superior analgesia when compared with
      intrathecal bupivacaine/diamorphine alone. There were no significant clinical
      differences between the group receiving bupivacaine 7.5 mg x ml(-1) and the group
      receiving ropivacaine 7.5 mg x ml(-1).

PMID- 11300388
TI  - Postoperative epidural analgesia in children after major orthopaedic surgery. A
      randomised study of the effect on PONV of two anaesthetic techniques: low and
      high dose i.v. fentanyl and epidural infusions with and without fentanyl.
AB  - BACKGROUND: The study was performed in order to improve postoperative pain
      management in children after major orthopaedic surgery. Two different anaesthetic
      techniques (sevoflurane-low fentanyl and propofol-higher fentanyl) and two
      different epidural mixtures (bupivacaine 1.5 mg ml(-1) and adrenaline 2 microg
      ml(-1) compared with bupivacaine 1 mg ml(-1), adrenaline 2 microg ml(-1) and
      fentanyl 2 microg ml(-1)) were investigated with regard to postoperative
      analgesia and side effects, primarily postoperative nausea and vomiting (PONV).
      METHODS: Forty-two children were randomised into one of three groups: sevoflurane
      anaesthesia and epidural solution with fentanyl (SBAF); sevoflurane anaesthesia
      and epidural solution without fentanyl (SBA); propofol anaesthesia and epidural
      solution without fentanyl (PBA). RESULTS: Including fentanyl in the epidural
      mixture resulted in excellent postoperative analgesia without any need of i.v.
      opioids. However, 7 out of 16 children were nauseated and needed antiemetic
      drugs. On average, a 55-75% higher dose of bupivacaine was necessary to assure
      adequate analgesia when an epidural mixture without fentanyl was used. In
      addition, significantly more children needed i.v. opioids. Under these conditions
      there was no significant difference in pain scoring between the groups. There was
      significantly less nausea and less use of antiemetic drugs in children having
      epidurals without fentanyl in the sevoflurane groups. The same tendency, although
      not significant, was observed in the whole material. Sevoflurane anaesthesia
      resulted in less PONV than propofol anaesthesia, probably due to the higher
      amount of intravenous fentanyl used with the latter. This difference was not
      significant due to the small number of children included. Incidence of pruritus
      related significantly to epidural fentanyl. CONCLUSION: A satisfactory
      postoperative analgesia can be achieved with both epidural mixtures used in the
      study. Epidural fentanyl results in better analgesia, but significantly more PONV
      and greater use of antiemetic drugs. Omitting epidural fentanyl results in less
      PONV, but significantly less profound analgesia and a need for additional
      treatment with i.v. opioids, in addition to a 55-75% higher epidural bupivacaine
      infusion. Both epidural treatments result in high and similar patient
      satisfaction and no serious complications. The study could not show any
      significant difference between the effect of sevoflurane and propofol anaesthesia
      on PONV.

PMID- 11300389
TI  - Ropivacaine 1 mg x ml(-1) does not decrease the need for epidural fentanyl after
      hip replacement surgery.
AB  - BACKGROUND: Ropivacaine is a new long-acting local anesthetic. Laboratory trials
      have demonstrated a synergistic analgesic effect between intrathecal opioids and
      local anesthetics. We tested the hypothesis that addition of ropivacaine 1 mg x
      ml(-1) to epidural fentanyl (10 microg x ml(-1)) postoperatively decreases the
      need for fentanyl, improves the quality of analgesia and decreases the side
      effects of fentanyl. METHODS: Forty patients were enrolled in this double-blind,
      randomized study to receive either fentanyl 10 microg x ml(-1) (group F) alone or
      fentanyl combined with ropivacaine 1 mg x ml(-1) (group R) for 20 h as an
      epidural infusion at TH12-L1 or L1-L2 for analgesia after hip replacement
      surgery. The patients were free to use a patient-controlled epidural analgesia
      device, which was programmed to infuse 3 ml of the study medication hourly and to
      allow a 3-ml bolus when needed (maximal hourly dose of fentanyl was 150 microg).
      The consumption of medication, visual pain scores at rest and on movement,
      hemodynamic and respiratory parameters, motor and sensory block, nausea, pruritus
      and sedation were recorded. RESULTS: There were no significant differences
      between the groups in the total mean fentanyl consumption (1.10+/-0.18 mg in
      group F, 1.08+/-0.31 mg in group R, 95% CI: -0.14 to 0.19, P = 0.774). The pain
      scores were similar at rest (median scores < or = 1) and on movement (median
      scores < or = 3). The adverse effects were similar and of a minor nature,
      consisting mostly of pruritus and nausea. CONCLUSION: Addition of ropivacaine 1
      mg x ml(-1) to epidural fentanyl 10 microg x ml(-1) did not significantly
      decrease the requirement for fentanyl administered for pain relief after hip
      replacement surgery.

PMID- 11300390
TI  - Neostigmine 50 microg kg(-1) with glycopyrrolate increases postoperative nausea
      in women after laparoscopic gynaecological surgery.
AB  - BACKGROUND: Neostigmine, used for reversal of neuromuscular block, has been
      implicated in the development of postoperative nausea and vomiting (PONV). The
      use of mivacurium, which does not require neostigmine reversal due to its
      metabolism by plasma cholinesterase, has made it possible to study the effect of
      neostigmine on PONV in a randomised, double-blind, placebo-controlled manner.
      METHODS: Ninety healthy women scheduled for laparoscopic gynaecological surgery
      were randomly allocated to two groups in a double-blind manner. One group was
      given neostigmine (50 microg kg(-1)) and glycopyrrolate (10 microg kg(-1)) (group
      NG), the other NaCl i.v. as placebo (group P) at the end of surgery when all the
      patients were spontaneously reversed to at least 75% of full muscle power. The
      risk of PONV was reduced by using low doses of opioids and ondansetron
      prophylaxis. All the patients were monitored and assessed for 24 h with regard to
      pain, nausea, vomiting and overall satisfaction. RESULTS: There was a
      statistically significant difference (P=0.03) in the occurrence of nausea during
      the first 6 h postoperatively between NG group (30%) and P group (11%), resulting
      in the more extensive use of antiemetic drugs in the NG group (28%) than in P
      group (7%) (P=0.01) in this period. There was no difference between the groups in
      the frequency of vomiting; seven nauseated patients had vomiting, four in group
      NG, three in group P. Total number of patients with PONV during the observation
      period of 24 h, usage of antiemetic rescue medication and overall patient
      satisfaction did not differ significantly between the groups. CONCLUSION: The
      results suggest that antagonism of neuromuscular block with a high dose of
      neostigmine increases postoperative nausea and the use of antiemetic drugs during
      the first 6 h after administration.

PMID- 11300391
TI  - A small dose of droperidol decreases postoperative nausea and vomiting in adults
      but cannot improve an already excellent patient satisfaction.
AB  - BACKGROUND: We evaluated whether or not 1) a routine prophylaxis with 20 microg x
      kg(-1) body weight of droperidol would efficiently prevent postoperative nausea
      and vomiting (PONV) after elective surgery in adults and 2) an efficient
      prophylaxis would improve patient satisfaction. METHODS: With approval of the
      local ethics committe and after having obtained informed written consent, 1334
      patients in a randomised, single-blinded fashion either received droperidol
      (group 1, n=665) or saline intravenously (group 2, n=669) 20 min before the end
      of a standard O2/N2O/fentanyl/isoflurane anaesthesia of at least 30 min duration.
      END POINTS: incidence of PONV during the first 24 h; individual episodes of
      nausea or vomiting, overall patient satisfaction with the procedure. RESULTS:
      Compared to saline, intravenous injection of droperidol substantially and
      significantly reduced the incidence of PONV from 30% to 20% (P<0.0001). Women
      suffered three times more frequently from PONV (10.5% vs. 30%, P<0.0001).
      Droperidol significantly reduced the incidence of PONV from 35.4% to 24.4% in
      women (relative risk reduction: 31%, P=0.0002), but not in men (13.1% vs. 8.2%,
      relative risk reduction: 37%, P=0.159)--without impact on overall patient
      satisfaction (98.8% vs. 97.1%, P=0.439). Distribution of surgical procedures,
      sex, age, height, weight and anaesthetic duration were not different between
      groups. To prevent one woman from suffering PONV, nine had to be treated
      prophylactically at an individual drug cost (German prices) of about Euro0.80 per
      woman. CONCLUSION: Routine PONV prophylaxis with 20 microg x kg(-1) body weight
      of droperidol is cost-efficient and appropriate in women but not in men.

PMID- 11300392
TI  - One way to ventilate patients during fibreoptic intubation.
AB  - Occasionally anaesthesiologists find themselves in situations where ventilation
      during intubation with a fibreoptic bronchoscope (FOB) is desirable. In order to
      ventilate the patient during the FOB intubation, we used a 90 degree angle swivel
      connector, normally used for fibreoptic bronchoscopia in an intubated patient.
      After a nasotracheal tube is placed with the tip in the oropharynx, ventilation
      of the patient is possible via this tube by closing the mouth and other nostril.
      The fibrescopic procedure is done through the right-angle connector with suction
      port and the tube is used to guide the tip of the FOB to the aditus laryngis. The
      method has been used in 7 patients who were impossible to intubate with a
      conventional procedure. In all patients ventilation was possible and intubation
      was performed in 5 min (range 1-15).

PMID- 11300393
TI  - Use of olprinone, a phosphodiesterase III inhibitor, in an asthmatic patient.
AB  - Phosphodiesterase (PDE) III exists in airway smooth muscles. In addition, PDEIII
      inhibitors have been suggested to relax airway smooth muscle by increasing
      intracellular cAMP concentrations. We report a successful use of olprinone, a
      PDEIII inhibitor, for treatment of an asthmatic attack. A 15-year-old male
      patient treated with oral theophylline 400 mg x d(-1) was anesthetized with
      propofol, fentanyl and ketamine for knee joint surgery. Immediately after
      tracheal intubation, an asthma attack occurred with peak airway pressure (Paw)>40
      cmH2O. Thus, propofol 20 mg was additionally given to increase anesthetic depth,
      and Paw gradually decreased to 30 cmH2O. In addition, we started monitoring
      bronchial cross-sectional area using a superfine fiberoptic bronchoscopic method
      previously reported. However, as Paw did not further decrease for 30 min,
      olprinone was intravenously infused (10 microg x kg(-1) x 10 min(-1) + 0.3 microg
      x kg(-1) x min(-1), total 5 mg). Olprinone infusion rapidly decreased peak Paw
      from 30 cmH2O to 24 cmH2O and increased bronchial cross-sectional area by 50%.
      These findings suggest that olprinone produced bronchodilation.

PMID- 11300394
TI  - Orthotopic liver transplantation in a patient with severe portopulmonary
      hypertension.
AB  - Liver transplantation in patients with severe portopulmonary hypertension (PPH)
      has been associated with mortality rates in the range of 70% to 80%. Preoperative
      long-term epoprostenol therapy reverses pulmonary hypertension and may be a
      valuable possibility to reduce mortality in patients with severe PPH undergoing
      orthotopic liver transplantation. We want to report a patient with severe PPH,
      who was treated with intravenous epoprostenol for an 8-month period, after which
      pulmonary vascular resistance had decreased from 12 to 3 Wood units.
      Nevertheless, the patient developed intractable perioperative right heart failure
      necessitating transient mechanical circulatory support. The patient was weaned
      from mechanical circulatory support, but died from another episode of acute right
      heart failure after 28 days. Complicated liver transplantation associated with
      major cardiovascular stress is obviously not tolerated in patients with severe
      portopulmonary hypertension even after preoperative long-term epoprostenol
      therapy.

PMID- 11300395
TI  - Rectal and oral acetaminophen.

PMID- 11300396
TI  - Oops--wrong dose of epidural clonidine in children!

PMID- 11300397
TI  - Acute dystonic reaction following general anaesthesia.

PMID- 11300398
TI  - Different approaches to brachial plexus block.

PMID- 11300399
TI  - Stability of biodegradable radioactive rhenium (Re-186 and Re-188) microspheres
      after neutron-activation.
AB  - Our objective was to determine if microspheres made from the biodegradable
      polymer poly(lactic acid) that contained rhenium could withstand the conditions
      of direct neutron activation necessary to produce therapeutic amounts of
      radioactive rhenium. The radiation damage of the polymer produced by gamma-doses
      of up to 1.05 MGy from Re-186 and Re-188 was examined by scanning electron
      microscopy and size exclusion chromatography. At a thermal neutron flux of 1.5 x
      10(13)n/cm2/s the microspheres melted after 3 h in the nuclear reactor, but
      suffered little damage after 1 h of radiation and released less than 5% of the
      radioactivity during incubation in buffer at 37 degrees C. The radioactive
      microspheres produced in this manner have a specific activity too low for
      radioembolization for treatment of liver tumors, but could be injected directly
      into tumors or applied topically to the wound bed of partially resected tumors.

PMID- 11300400
TI  - Application of X-ray fluorescence spectrometry in multielement analysis of rubber
      samples.
AB  - Elemental analysis of rubber samples is rather difficult, but XRF spectrometry
      offers some advantages relative to other more popular chemical instrumental
      techniques due to relatively simple sample preparation. For the excitation
      annular radionuclide photon sources of 55Fe and 109Cd were used. The analyses of
      metal content in samples of natural latex have been performed in order to
      investigate the relation between the low specific resistivity of the latex and
      the respective metal content. The results are presented and discussed.

PMID- 11300401
TI  - EPR investigation of the gamma-ray irradiated natural and tanned collagen.
AB  - Free radicals produced in natural and tanned collagen by gamma-ray irradiation
      within 1-15 kGy absorbed dose ranges were investigated by EPR spectroscopy.
      Tanned collagen was prepared using formaldehyde as well as aluminum basic salts
      [Al(OH)SO4] tanning processes. Both natural and formaldehyde-tanned irradiated
      collagen show the same kind of EPR spectrum consisting of a single broad,
      slightly asymmetric line. Irradiated collagen tanned by aluminum basic salts
      process displayed a complex EPR spectrum consisting of a superposition of broad
      and narrow lines. A computer simulation of this spectrum allowed to evidence the
      presence of seven different kinds of paramagnetic centers, including those
      observed in the irradiated natural collagen. Corresponding Spin Hamiltonian
      parameters (g-factor, hyperfine splitting constant) as well as relative
      concentrations of these centers were calculated. Experimentally determined
      relative concentrations display a positive correlation with the absorbed dose
      described by a linear-type dependence. After three weeks of storage at room
      temperature, the concentration of some centers diminished by about 50%. The
      possible nature of these centers is discussed in connection with the local
      structure of the tanned collagen.

PMID- 11300402
TI  - Preliminary studies on combining the K and L XRF methods for in vivo bone lead
      measurement.
AB  - Lead is a toxic material that invokes irreversible neurological problems. Once
      ingested, lead accumulates in the bones. To study detailed lead poisoning effects
      it is essential to have an in vivo bone lead measurement tool with a small
      minimum detectable concentration (MDC). Both K- and L-based XRF methods for the
      tibia bone have been suggested and developed in the past and are presently in
      use. In this work a combined K and L XRF method for the tibia bone is proposed.
      The proposed system consists of a 109Cd point source and Ge and Si(Li) detectors
      for optimum detection of the K and L X-rays, respectively. Experimental and Monte
      Carlo simulated results are given here for a prototype combined K and L XRF
      system. This system promises to yield a better MDC and the possibility of
      obtaining information on the near-surface bone lead content as well as the
      average lead content throughout the bone.

PMID- 11300403
TI  - The natBr(p,x) (73,75)Se nuclear processes: a convenient route for the production
      of radioselenium tracers relevant to amino acid labelling.
AB  - A possible route for the production of no-carrier-added (n.c.a.) 73Se (T(1/2) =
      7.1 h) and 75Se (120 d) is introduced. D,L-2-Amino-4-([73Se]methyl-seleno)
      butanoic acid (D,L-[73Se]selenomethionine) with an overall radiochemical yield of
      > 40% could be prepared via a 3-step polymer-supported synthesis after successful
      separation of 73Se from KBr targets. Excitation functions for the natBr(p,x)
      (72,73,75)Se processes were measured from threshold up to 100 MeV utilizing
      pellets of pressed KBr. Targets were irradiated at the NAC cyclotron with proton
      beams having primary energies of 40.4, 66.8 and 100.9 MeV. The calculated 73Se
      yield (EOB) for 1 h irradiation in 1 microA of beam at the optimum proton energy
      range of 62-->42 MeV is 81.4 MBq (2.2 mCi), and the calculated 75Se yield (EOB)
      for the overall range 62 MeV-->threshold for the same irradiation conditions is
      0.97 MBq (0.026 mCi).

PMID- 11300404
TI  - Cyclotron production of 67Ga(III) with a tandem natGe-natZn target.
AB  - Production of 67Ga(III) at the National Accelerator Centre is by proton
      bombardment of a natZn target, and uses 15-20 h of cyclotron beam time per
      production. A study was undertaken to use a tandem natGe-natZn target to produce
      the same amount of 67Ga, but using less beam time (7-8 h). 67Ga(III) was
      separated from the tandem target material by a method based on acid dissolution
      of the target and chromatography on an organic polymer resin (Amberchrom CG-71cd)
      containing no ion exchange groups. The separated 67Ga(III) has high radionuclidic
      purity and complies with the British and US Pharmacopoeia requirements for
      chemical purity.

PMID- 11300405
TI  - Extraction of cadmium and iodocadmat species by di(2-ethylhexyl) phosphoric acid
      from perchloric and phosphoric media.
AB  - We have investigated the extraction of cadmium with di(2-ethylhexyl) phosphoric
      acid (HDEHP) in various solvents from perchloric and phosphoric solutions. The
      distribution coefficient D obtained is not very dependent on the nature and the
      polarity of the diluent used. The extraction of Cd(II) by HDEHP dissolved in
      benzene, from sulfophosphoric solutions shows the absence of sulfuric or mixed
      sulfophosphoric complexes of the metal. However, the presence of iodide anions in
      aqueous perchloric or phosphoric media results in enhanced extraction coefficient
      of cadmium with HDEHP (HX) in benzene. The extracted species were found to be
      CdIX,3(HX)2 and CdI2,3(HX)2 and their formation constants are 0.033 and 0.036,
      respectively. The recovery of cadmium from phosphoric medium by tributylphosphate
      (TBP), trioctyl phosphine oxide (TOPO), triphenyl phosphine oxide (TPPO),
      diphenylamine or their mixtures with HDEHP is lesser than with HDEHP alone.

PMID- 11300406
TI  - Automated synthesis and purification of [18F]bromofluoromethane at high specific
      radioactivity.
AB  - [18F]Bromofluoromethane was synthesised from dibromomethane by substitution of
      bromine with [18F]fluoride. The synthesis and separation of the
      [18F]bromofluoromethane were automated. [18F]Bromofluoromethane was used to
      convert a phenolic and a thiophenolic precursor into a labelled ether and
      thioether, respectively. The specific radioactivity of these labelled products
      was determined with both high-performance liquid chromatography (with UV
      absorbance detection) and liquid chromatography (with mass spectrometric
      detection). The median for the specific radioactivity, corrected at the end of
      radionuclide production, was 934GBq/micromol (range 40-9900 GBq/micromol; n =
      83).

PMID- 11300407
TI  - [11C]Formaldehyde revisited: considerable concurrent [11C]formic acid formation
      in the low-temperature conversion of.
AB  - The reduction of [11C]carbon dioxide with lithium aluminium hydride in diethyl
      ether at temperatures ranging from -56 degrees C to 19 degrees C was studied. In
      contrast to what others have reported, considerable amounts of [11C]formic acid
      were found at all studied temperatures.

PMID- 11300408
TI  - Rapid non-destructive quantitative estimation of urania/thoria in mixed thorium
      uranium di-oxide pellets by high-resolution gamma-ray spectrometry.
AB  - A non-destructive technique using high-resolution gamma-ray spectrometry has been
      standardised for quantitative estimation of uranium/thorium in mixed (ThO2-UO2)
      fuel pellets of varying composition. Four gamma energies were selected; two each
      from the uranium and thorium series and the time of counting has been optimised.
      This technique can be used for rapid estimation of U/Th percentage in a large
      number of mixed fuel pellets from a production campaign.

PMID- 11300409
TI  - Transfer coefficient measurements of uranium to the organs of Wistar rats, as a
      function of the uranium content in the food.
AB  - Groups of animals (Wistar rats) were fed with rations doped with uranyl nitrate
      at concentrations ranging from 0.5 to 100 ppm. The uranium content in the ashes
      of the organs was measured by the neutron-fission track counting technique. The
      most striking result is that the transfer coefficients, as a function of the
      uranium concentration, exhibit a concave shape with a minimum around 20 ppm-U for
      all organs. Explanations to interpret this finding are tentatively given.

PMID- 11300410
TI  - TL response study of the CaSO4:Dy pellets with graphite for dosimetry in beta
      radiation and low-energy photons fields.
AB  - The CaSO4:Dy is a good thermoluminescent dosimeter because of its high
      sensitivity and low cost. With graphite in the pellets it is possible to reduce
      the energy dependence. The sensitivity and energy dependence of the different
      thicknesses of CaSO4:Dy pellets was studied with different amounts of graphite.
      The results have shown the optimal quantity of the graphite and the appropriate
      thickness of the pellets that can be used in dosimetry of beta field, photons or
      both simultaneously.

PMID- 11300412
TI  - Investigations on neutron-induced prompt gamma ray analysis of bulk samples.
AB  - A systematic investigation was carried out for the improvement of the prompt
      gamma interrogation method used for contraband detection by the pulsed
      fast/thermal neutron analysis (PFTNA) technique. Optimizations of source detector
      shielding and geometry, role of the type and dimension of the gamma detector,
      attenuation of neutrons and gamma rays in bulky samples were also studied.
      Results obtained for both the shielding materials and elemental content of
      cocaine simulants have been compared with the values calculated by the MCNP-4A
      code.

PMID- 11300411
TI  - Theoretical foundation for a simple method for simultaneous measurements of the
      unattached fraction and activity median diameter of attached radon progeny.
AB  - Calculation of lung dose from established lung dosimetry models requires use of
      the unattached fraction of potential alpha energy concentration (PAEC) of radon
      progeny and the activity median diameter (AMD) of attached radon progeny, in
      addition to the total PAEC. In the present work, for indoor environments without
      the nucleation mode of aerosols, a method based on the wire screen penetration
      theory using two wire screens and a filter is proposed for simultaneous
      measurements of these two parameters. It is shown that the traditional wire
      screen method can overestimate or sometimes underestimate the unattached
      fraction, depending on the properties of the wire screen and the true unattached
      fraction. The present method eliminates such uncertainties.

PMID- 11300413
TI  - Attenuation coefficients of soils and some building materials of Bangladesh in
      the energy range 276-1332 keV.
AB  - The linear and mass attenuation coefficients of different types of soil, sand,
      building materials and heavy beach mineral samples from the Chittagong and Cox's
      Bazar area of Bangladesh were measured using a high-resolution HPGe detector and
      the gamma-ray energies 276.1, 302.8, 356.0, 383.8, 661.6 and 1173.2 and 1332.5
      keV emitted from point sources of 133Ba, 137Cs and 60Co, respectively. The linear
      attenuation coefficients show a linear relationship with the corresponding
      densities of the samples studied. The variations of the mass attenuation
      coefficient with gamma-ray energy were exponential in nature. The measured mass
      attenuation coefficient values were compared with measurements made in other
      countries for similar kinds of materials. The values are in good agreement with
      each other in most cases.

PMID- 11300414
TI  - A laboratory study of the transfer of 234U and 238U during water-rock
      interactions in the Carnmenellis granite (Cornwall, England) and implications for
      the interpretation of field data.
AB  - Laboratory time-scale experiments were conducted on gravels from the Carnmenellis
      granite, Cornwall, England, with the purpose of evaluating the release of natural
      uranium isotopes to the water phase. The implications of these results for the
      production of enhanced 234U/235U activity ratios in Cornish groundwaters are
      discussed. It is suggested that the 234U/238U lab data can be used to interpret
      activity ratios from Cornwall, even when the observed inverse relationship
      between dissolved U and 234U/235U in leachates/etchates is taken into account.

PMID- 11300415
TI  - An analytical model for the SO2- centre, ESR signal at g = 2.0057 in carbonates.
AB  - Detailed experiments were conducted to test the behaviour of the ESR signal at
      the g-value of 2.0057 in corals after irradiation and heating. On the basis of
      the results an analytical model for this signal was developed. We assume the
      existence of a precursor to the SO2- radical. On irradiation traps are produced,
      some in the precursor state and some in the radical state. Heating then causes
      transfer of electrons into the precursor state, from the precursor state into the
      radical state and out of the radical state into a base state. On the base of this
      model, we suggest that the signal at g = 2.0057 can be applied for dating. Our
      first dating attempts on corals delivered promising results for the suggested
      procedure.

PMID- 11300416
TI  - Care of the adult with congenital heart disease: introduction.

PMID- 11300417
TI  - Summary of recommendations--care of the adult with congenital heart disease.

PMID- 11300418
TI  - Task force 1: the changing profile of congenital heart disease in adult life.

PMID- 11300419
TI  - Task force 2: special health care needs of adults with congenital heart disease.

PMID- 11300420
TI  - Task force 3: workforce description and educational requirements for the care of
      adults with congenital heart disease.

PMID- 11300421
TI  - Task force 4: organization of delivery systems for adults with congenital heart
      disease.

PMID- 11300422
TI  - Task force 5: adults with congenital heart disease: access to care.

PMID- 11300423
TI  - Surgical anterior ventricular endocardial restoration (SAVER) in the dilated
      remodeled ventricle after anterior myocardial infarction. RESTORE group.
      Reconstructive Endoventricular Surgery, returning Torsion Original Radius
      Elliptical Shape to the LV.
AB  - OBJECTIVES: The goal of this study was to evaluate the safety and efficacy of
      surgical anterior ventricular endocardial restoration (SAVER). The procedure
      excludes noncontracting segments in the dilated remodeled ventricle after
      anterior myocardial infarction. BACKGROUND: Anterior infarction leads to change
      in ventricular shape and volume. In the absence of reperfusion, dyskinesia
      develops. Reperfusion by thrombolysis or angioplasty leads to akinesia. Both lead
      to congestive heart failure by dysfunction of the remote muscle. The akinetic
      heart rarely undergoes surgical repair. METHODS: A new international group of
      cardiologists and surgeons from 11 centers (RESTORE group) investigated the role
      of SAVER in patients after anterior myocardial infarction. From January 1998 to
      July 1999, 439 patients underwent operation and were followed for 18 months.
      Early outcomes of the procedure and risk factors were investigated. RESULTS:
      Concomitant procedure included coronary artery bypass grafting in 89%, mitral
      valve (MV) repair in 22% and MV replacement in 4%. Hospital mortality was 6.6%,
      and few patients required mechanical support devices such as intraaortic balloon
      counterpulsation (7.7%), left ventricular assist device (0.5%) or extracorporeal
      membrane oxygenation (1.3%). Postoperatively, ejection fraction increased from 29
      +/- 10.4 to 39 +/- 12.4%, and left ventricular end systolic volume index
      decreased from 109 +/- 71 to 69 +/- 42 ml/m2 (p < 0.005). At 18 months, survival
      was 89.2%. Time related survival at 18 months was 84% in the overall group and
      88% among the 421 patients who had coronary artery bypass grafting or MV repair.
      Freedom from readmission to hospital for congestive heart failure at 18 months
      was 85%. Risk factors for death at any time after the operation included older
      age, MV replacement and lower postoperative ejection fraction. CONCLUSIONS:
      Surgical anterior ventricular endocardial restoration is a safe and effective
      operation in the treatment of the remodeled dilated anterior ventricle after
      anterior myocardial infarction.

PMID- 11300424
TI  - Is it time for a randomized trial of surgical treatment of ischemic heart
      failure?

PMID- 11300425
TI  - Beneficial effects of ramipril on left ventricular end-diastolic and end-systolic
      volume indexes after uncomplicated invasive revascularization are associated with
      a reduction in cardiac events in patients with moderately impaired left
      ventricular function and no clinical heart failure.
AB  - OBJECTIVES We sought to assess the effect of ramipril on left ventricular (LV)
      volumes, and the clinical significance thereof, in patients with moderate LV
      dysfunction and no clinical heart failure undergoing invasive revascularization
      for chronic stable angina. BACKGROUND: It is unsettled whether treatment with an
      angiotensin-converting enzyme inhibitor has an impact on LV volumes in this
      patient group, and, if so, whether this is associated with the clinical outcome.
      METHODS: A total of 133 patients with a left ventricular ejection fraction (LVEF)
      between 0.30 and 0.50 and no clinical heart failure undergoing invasive
      revascularization for chronic stable angina were randomized to receive ramipril
      10 mg once daily or placebo and were followed for a median of 33 months with
      echocardiography at baseline and 3, 12 and 24 months postoperatively. RESULTS:
      Repeated measures analysis of all time points showed that ramipril significantly
      reduced the end-diastolic volume index (EDVI) (p = 0.032) and end-systolic volume
      index (ESVI) (p = 0.006) as compared with placebo. Ramipril also reduced the
      incidence of the triple composite end point of cardiac death, acute myocardial
      infarction or development of heart failure (p = 0.046). Cox regression analysis,
      controlling for baseline LVEF and assignment to ramipril, revealed: 1) that
      increases in EDVI and ESVI up to three months predicted an increasing risk of a
      future adverse clinical outcome; and 2) that the benefit with ramipril on
      clinical outcome was partly dependent on a reduction in LV volumes. CONCLUSIONS:
      Even in this patient group, LV dilation may supervene and lead to an adverse
      clinical outcome. Ramipril reduces the postoperative increase in LV volumes and
      may thereby improve clinical outcome.

PMID- 11300426
TI  - Effects of intravenous brain natriuretic peptide on regional sympathetic activity
      in patients with chronic heart failure as compared with healthy control subjects.
AB  - OBJECTIVES: We sought to assess the effects of brain natriuretic peptide (BNP) on
      systemic and regional sympathetic nervous activity (SNA) in both patients with
      congestive heart failure (CHF) and healthy control subjects. BACKGROUND: Although
      the response of SNA to atrial natriuretic peptide (ANP) has been well documented,
      the response of SNA to BNP is largely unknown. METHODS: We assessed cardiac and
      whole-body SNA using the norepinephrine (NE) tracer dilution method before and
      after infusion of two doses of BNP (3 and 15 ng/kg body weight per min) in 11
      patients with stable CHF (ejection fraction 24 +/- 2%) and 12 age-matched healthy
      control subjects. In addition, renal SNA and hemodynamic variables were assessed
      at baseline and after the higher BNP dose. RESULTS: Low dose BNP did not change
      blood pressure or whole-body NE spillover, but reduced cardiac NE spillover in
      both groups by 32 +/- 13 pmol/min (p < 0.05). In both groups, high dose BNP
      reduced pulmonary capillary pressure by 5 +/- 1 mm Hg (p < 0.001) and mean
      arterial pressure by 6 +/- 3 mm Hg (p < 0.05), without a concomitant increase in
      whole-body NE spillover; however, cardiac NE spillover returned to baseline
      levels. Renal NE spillover remained virtually unchanged in healthy control
      subjects (501 +/- 120 to 564 +/- 115 pmol/min), but was reduced in patients with
      CHF (976 +/- 133 to 656 +/- 127 pmol/min, p < 0.01). CONCLUSIONS: Our results
      demonstrate a sympathoinhibitory effect of BNP. Cardiac sympathetic inhibition
      was observed at BNP concentrations within the physiologic range, whereas high
      dose BNP, when arterial and filling pressures fell and reflex sympathetic
      stimulation was expected, systemic and cardiac SNA equated to baseline values.
      There was inhibition of renal SNA in patients with CHF, but not in healthy
      control subjects. Whether this effect is specific to BNP or related to reduced
      filling pressure remains to be determined.

PMID- 11300427
TI  - Effect of spironolactone on plasma brain natriuretic peptide and left ventricular
      remodeling in patients with congestive heart failure.
AB  - OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral
      factors and left ventricular remodeling in patients with congestive heart failure
      (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural
      remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported
      to reduce mortality in patients with CHF, but its influence on left ventricular
      remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to
      moderate nonischemic CHF were randomly divided into two groups that received
      treatment with spironolactone (n = 20) or placebo (n = 17). We measured left
      ventricular volume and mass before treatment and after four months of treatment.
      We also measured the plasma levels of neurohumoral factors, such as atrial
      natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma
      procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial
      fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased
      and ejection fraction was significantly increased in the spironolactone group,
      while there were no changes in the placebo group. Plasma levels of ANP, BNP and
      PIIINP were significantly decreased after spironolactone treatment, but were
      unchanged in the placebo group. There was a significant positive correlation
      between the changes of PIIINP and changes of the left ventricular volume index (r
      = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p =
      0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that
      four months of treatment with spironolactone improved the left ventricular volume
      and mass, as well as decreased plasma level of BNP, a biochemical marker of
      prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone
      has an important role in the process of left ventricular remodeling in
      nonischemic patients with CHF.

PMID- 11300429
TI  - Postinfarctional remodeling: increased dye intensity in the myocardial risk area
      after angioplasty of infarct-related coronary artery is associated with reduction
      of ventricular volumes.
AB  - OBJECTIVES: We sought to evaluate if angiographic dye videointensity of the risk
      area during percutaneous transluminal coronary angioplasty (PTCA) of the infarct
      related artery (IRA) relates to remodeling. BACKGROUND: Poor reflow after
      myocardial infarction (MI) predicts worse ventricular remodeling. METHODS: Fifty
      three patients with a first anterior MI and isolated disease of the left anterior
      descending (LAD), who underwent "primary" (n = 14), "rescue" (n = 7) or "late"
      (after 10 +/- 4 days, n = 32) PTCA, were retrospectively selected. In 10 patients
      prospectively collected, we assessed Doppler flow velocities and Doppler flow
      reserve (DFR), relating them to the videointensity technique. Coronary stenosis
      and TIMI flow were determined, and echocardiographic volumes (end-diastolic and
      end-systolic volume indexes) and regional asynergy were computed before hospital
      discharge (baseline) and at six months. Assuming higher peak videointensity
      reflects greater myocardial blood volume, a 1- to 5-point (poor-optimal)
      perfusion scale was devised. RESULTS: The correlation of Doppler peak velocity
      and DFR with videointensity was significant (r = 0.58, p = 0.007 and r = 0.71, p
      < 0.001, respectively). Patients were subdivided into group A (increased
      videointensity post-PTCA > or = 1.5 points, n = 29) and group B (unchanged
      videointensity, n = 24). Analysis of variance showed a time-group interaction for
      end-diastolic volume index (-4.6 +/- 23% vs. +22 +/- 22%, p = 0.003) and end
      systolic volume index (-3.05 +/- 11.1% vs. +4.1 +/- 12.5%, p = 0.027). There was
      no interaction for changes in LAD stenosis (p = 0.39) and TIMI flow after PTCA (p
      = 0.27), or regional asynergy at six months (p = 0.31). CONCLUSIONS: Angiographic
      dye videointensity in the risk area correlates with Doppler peak velocity and
      DFR, and its increase after PTCA of IRA has a limiting effect on ventricular
      volumes, independent of coronary stenosis resolution, changes in Thrombolysis In
      Myocardial Infarction (TIMI) flow or extent of regional asynergy.

PMID- 11300428
TI  - Aspirin inhibits the acute venodilator response to furosemide in patients with
      chronic heart failure.
AB  - OBJECTIVES: We sought to determine the effect of aspirin on the venodilator
      effect of furosemide in patients with chronic heart failure (CHF) BACKGROUND:
      Furosemide has an acute venodilator effect preceding its diuretic action, which
      is blocked by nonsteroidal anti-inflammatory, drugs. The ability of therapeutic
      doses of aspirin to block this effect of furosemide in patients with CHF has not
      been studied. For comparison, the venodilator response to nitroglycerin (NTG) was
      also studied. METHODS: Eleven patients with CHF were randomized to receive
      placebo, aspirin at 75 mg/day or aspirin at 300 mg/day for 14 days in a double
      blind, crossover study. The effect of these pretreatments on the change in
      forearm venous capacitance (FVC) after 20 mg of intravenous furosemide was
      measured over 20 min by using venous occlusion plethysmography. In a second
      study, the effect of 400 microg of sublingual NTG on FVC was documented in 11
      similar patients (nine participated in the first study). RESULTS: Mean arterial
      pressure, heart rate and forearm blood flow did not change in response to
      furosemide. After placebo pretreatment, furosemide caused an increase in FVC of
      2.2% (95% confidence interval [CI] -0.9% to 5.2%; mean response over 20 min). By
      comparison, FVC fell by -1.1% (95% CI -4.2% to 1.9%) after pretreatment with
      aspirin at 75 mg/day, and by -3.7% (95% CI -6.8% to -0.7%) after aspirin at 300
      mg/day (p = 0.020). In the second study, NTG increased FVC by 2.1% (95% CI -1.6%
      to 5.8%) (p = 0.95 vs. furosemide). CONCLUSIONS: In patients with CHF,
      venodilation occurs within minutes of the administration of intravenous dose of
      furosemide. Our observation that aspirin inhibits this effect further questions
      the use of aspirin in patients with CHF.

PMID- 11300430
TI  - Evidence for functional presynaptic alpha-2 adrenoceptors and their down
      regulation in human heart failure.
AB  - OBJECTIVES: The aim of this study was to investigate the role of peripheral
      presynaptic alpha-2 adrenergic receptors in modulating norepinephrine (NE)
      release in congestive heart failure (CHF). BACKGROUND: Activation of the
      sympathetic nervous system is a hallmark of CHF. Clonidine, an imidazoline and
      adrenergic agonist with high selectivity for the alpha-2 adrenoceptor, has been
      shown to reduce generalized sympathetic activity in heart failure after
      parenteral administration. If it could be shown that peripheral presynaptic alpha
      2 adrenoceptors are inhibitory to NE release, then they could be targeted for
      future therapy, and as a corollary, potentially circumvent unwanted side effects
      arising from stimulation of alpha-2 adrenoceptors in the brain. Additionally, it
      could be concluded that these receptors form the basis for an auto-inhibitory
      feedback to further NE release. METHODS: Fifteen healthy volunteers and 10
      patients with heart failure received intra-arterial clonidine via the brachial
      artery (0.05 microg and 0.48 microg/100 ml forearm/min). Radio-tracer techniques
      were employed for studying NE kinetics. RESULTS: Intra-arterial clonidine caused
      a dose-dependent decrease in forearm spillover of NE in healthy individuals (low
      dose, high dose: 26%, 49%: p < 0.05, p < 0.001, respectively). In the patient
      group, no decrease in forearm spillover was demonstrated after local
      administration. The difference in response between the two groups was
      statistically significant (p = 0.004). CONCLUSIONS: Peripheral sympathoneural
      alpha-2 adrenoceptors are functionally important in inhibiting NE release in the
      healthy human. In heart failure, this function is lost. This finding offers
      further insights into the mechanisms responsible for high circulating levels of
      NE in patients with heart failure. In addition, it suggests that selective
      targeting of peripheral presynaptic alpha-2 adrenoceptors will not achieve
      sympathoinhibition in heart failure.

PMID- 11300431
TI  - Angiography of potential cardiac donors.
AB  - OBJECTIVES: This retrospective review of organ donor records was designed to
      evaluate the practice of donor angiography in one organ procurement organization
      and determine the outcomes of angiography and its impact on the timing of the
      organ donation process. BACKGROUND: Concerns about transmission of
      atherosclerosis from donor to recipient have been heightened by the increasing
      prevalence of older donors. Guidelines that advocate the use of angiography in
      specific settings have been published, but no formal large-scale review has been
      performed. METHODS: For the period January 1993 through June 1997, we reviewed
      all New England Organ Bank records of donors between the ages of 40 and 65
      including any from whom at least one solid organ was procured. Data abstracted
      included the presence of risk factors, timing of the evaluation process and
      angiographic findings. RESULTS: Coronary angiography was performed in 119 donors
      aged 40 and older; 64.7% of these hearts were transplanted. Thirty-eight hearts
      were transplanted from donors not subjected to angiography and outcomes were
      poorer compared with donors who underwent angiography. Advanced donor age was the
      only significant predictor of coronary artery disease. The duration of the
      procurement process was not prolonged by the performance of angiography.
      CONCLUSIONS: Donor coronary angiography does not complicate the donation process.
      Older donor age is the most powerful predictor of coronary artery disease and may
      explain prior observations of poorer outcome with older donor hearts. These
      factors should be considered when angiography is performed as part of the heart
      donor evaluation.

PMID- 11300432
TI  - Ticlopidine versus aspirin after myocardial infarction (STAMI) trial.
AB  - OBJECTIVES: We sought to compare the efficacy of aspirin and ticlopidine in
      survivors of acute myocardial infarction (AMI) treated with thrombolysis.
      BACKGROUND: The role of ticlopidine in secondary prevention after AMI has not yet
      been explored. METHODS: Of 4,696 patients with AMI treated with thrombolysis who
      were screened, 261 died in the hospital (5.6%) and 1,470 were enrolled in this
      randomized, double-blind, multicenter trial and allocated to treatment with
      either aspirin (160 mg/day) or ticlopidine (500 mg/day). The most frequent
      reasons for exclusion were refusal to give informed consent, planned myocardial
      revascularization, risk of noncompliance with study procedures, need for
      anticoagulant therapy and contraindications to the study treatments. The primary
      end point was the first occurrence of any of the following events during the six
      month follow-up: fatal and nonfatal AMI, fatal and nonfatal stroke, angina with
      objective evidence of myocardial ischemia, vascular death or death due to any
      other cause. RESULTS: The primary end point was recorded in 59 (8.0%) of the 736
      aspirin-treated and 59 (8.0%) of the 734 ticlopidine-treated patients (p =
      0.966). Vascular death was the first event in five patients taking aspirin and in
      six patients taking ticlopidine (0.7% vs. 0.8%; p = NS); nonfatal AMI in 18 and 8
      (2.4% vs. 1.1%; p = 0.049); nonfatal stroke in 3 and 4 (0.4% vs. 0.5%; p = NS);
      and angina in 33 and 40 (4.5% vs. 5.4%; p = NS), respectively. The frequency of
      adverse reactions was not significantly different between the two groups.
      CONCLUSIONS: No difference was found between the ticlopidine and aspirin groups
      in the rate of the primary combined end point of death, recurrent AMI, stroke and
      angina.

PMID- 11300433
TI  - The effect of aspirin on C-reactive protein as a marker of risk in unstable
      angina.
AB  - OBJECTIVES: This study was designed to assess the interaction between aspirin and
      C-reactive protein (CRP) release in unstable angina. BACKGROUND: C-reactive
      protein release in acute coronary syndromes may be a response to myocardial
      necrosis or may reflect the inflammatory process that drives atherogenesis.
      Aspirin has the potential to influence CRP release, either by its anti
      inflammatory activity or by reducing myocardial necrosis. The clinical
      significance of this potential interaction has not previously been tested.
      METHODS: We conducted a prospective cohort study of 304 consecutive patients
      admitted with non-ST-elevation acute coronary syndromes. Serial blood samples
      were obtained for CRP and troponin I assay. End points were cardiac death and
      nonfatal myocardial infarction during follow-up for 12 months. RESULTS: A total
      of 174 patients (57%) were taking aspirin before admission. Patients taking
      aspirin had lower troponin I concentrations throughout the sampling period, only
      45 (26.0%) having concentrations >0.1 mg/l compared with 48 (37.8%) patients not
      taking aspirin (p = 0.03). Maximum CRP concentrations were also lower in patients
      taking aspirin (8.16 mg/l [3.24 to 24.5]) than in patients not taking aspirin
      (11.3 mg/l [4.15 to 26.1]), although the difference was not significant. However,
      there was significant interaction (p = 0.04) between prior aspirin therapy and
      the predictive value of CRP concentrations for death and myocardial infarction at
      12 months. Thus, odds ratios (95% confidence intervals) for events associated
      with an increase of 1 standard deviation in maximum CRP concentration were 2.64
      (1.22-5.72) in patients not pretreated with aspirin compared with 0.98 (0.60
      1.62) in patients pretreated with aspirin. CONCLUSIONS: The association between
      CRP and cardiac events in patients with unstable angina is influenced by
      pretreatment with aspirin. Modification of the acute-phase inflammatory responses
      to myocardial injury is the major mechanism of this interaction.

PMID- 11300434
TI  - Recurrent unstable angina after directional coronary atherectomy is related to
      the extent of initial coronary plaque inflammation.
AB  - OBJECTIVES: This study was performed to evaluate the relationship between plaque
      inflammation of the initial culprit lesion and the incidence of recurrent angina
      for one year after directional coronary atherectomy (DCA). BACKGROUND: A positive
      correlation between coronary plaque inflammation and angiographic restenosis has
      been reported. METHODS: A total of 110 patients underwent DCA. Cryostat sections
      were immunohistochemically stained with monoclonal antibodies CD68 (macrophages),
      CD-3 (T lymphocytes) and alpha-actin (smooth muscle cells [SMCs]). The SMC and
      macrophage contents were planimetrically quantified as a percentage of the total
      tissue area. T lymphocytes were counted as the number of cells/mm2. The patients
      were followed for one year to document recurrent unstable angina pectoris (UAP)
      or stable angina pectoris (SAP). RESULTS: Recurrent UAP developed in 16 patients,
      whereas recurrent SAP developed in 17 patients. The percent macrophage areas were
      larger in patients with recurrent UAP (27 +/- 12%) than in patients with
      recurrent SAP (8 +/- 4%; p = 0.0001) and those without recurrent angina (18 +/-
      14%; p = 0.03). The number of T lymphocytes was also greater in patients with
      recurrent UAP (25 +/- 14 cells/mm2) than in patients with recurrent SAP (14 +/- 8
      cells/mm2; p = 0.02) and those without recurrent angina (14 +/- 12 cells/mm2; p =
      0.002). Multiple stepwise logistic regression analysis identified macrophage
      areas and T lymphocytes as independent predictors for recurrent UAP. CONCLUSIONS:
      There is a positive association between the extent of initial coronary plaque
      inflammation and the recurrence of unstable angina during long-term follow-up
      after DCA. These results underline the role of ongoing smoldering plaque
      inflammation in the recurrence of unstable angina after coronary interventions.

PMID- 11300435
TI  - Increased local temperature in human coronary atherosclerotic plaques: an
      independent predictor of clinical outcome in patients undergoing a percutaneous
      coronary intervention.
AB  - OBJECTIVES: We investigated the midterm clinical significance of human coronary
      atherosclerotic plaques temperature after a successful percutaneous coronary
      intervention. BACKGROUND: Previous studies have shown an increased temperature in
      human atherosclerotic plaques. However, the prognostic significance of
      atherosclerotic plaque temperature in patients undergoing a successful
      percutaneous intervention is unknown. METHODS: We prospectively investigated the
      relation between the temperature difference (deltaT) between the atherosclerotic
      plaque and the healthy vessel wall and event-free survival among 86 patients
      undergoing a successful percutaneous intervention. Temperature was measured by a
      thermography catheter, as previously validated. The study group consisted of
      patients with effort angina (EA) (34.5%), unstable angina (UA) (34.5%) and acute
      myocardial infarction (AMI) (30%). RESULTS: The deltaT increased progressively
      from EA to AMI (0.132 +/- 0.18 degrees C in EA, 0.637 +/- 0.26 degrees C in UA
      and 0.942 +/- 0.58 degrees C in AMI). The median clinical follow-up period was
      17.88 +/- 7.16 months. The deltaT was greater in patients with adverse cardiac
      events than in patients without events (deltaT: 0.939 +/- 0.49 degrees C vs.
      0.428 +/- 0.42 degrees C; p < 0.0001). The deltaT was a strong predictor of
      adverse cardiac events during the follow-up period (odds ratio 2.14, p = 0.043).
      The threshold of the deltaT value, above which the risk for an adverse cardiac
      event was significantly increased, was 0.5 degrees C. The incidence of adverse
      cardiac events in patients with deltaT > or = 0.5 degrees C was 41%, as compared
      with 7% in patients with deltaT < 0.5 degrees C (p < 0.001). CONCLUSIONS:
      Increased local temperature in atherosclerotic plaques is a strong predictor of
      an unfavorable clinical outcome in patients with coronary artery disease
      undergoing percutaneous interventions.

PMID- 11300436
TI  - Extensive development of vulnerable plaques as a pan-coronary process in patients
      with myocardial infarction: an angioscopic study.
AB  - OBJECTIVES: To test our hypothesis that the development of vulnerable plaques is
      not limited to the culprit lesions, but is a pan-coronary process, we directly
      observed all three major coronary arteries by angioscopy and evaluated the
      prevalence of yellow plaques in patients with myocardial infarction (MI).
      BACKGROUND: Although pathologic studies have suggested that the disruption of
      atheromatous plaque plays a major role in the development of acute MI, the
      prevalence of yellow plaques in the whole coronary arteries of patients with MI
      has not been clarified. METHODS: Thirty-two patients undergoing follow-up
      catheterization one month after the onset of MI were prospectively and
      consecutively enrolled in this study. The prevalence of yellow plaques and
      thrombus in the major coronary arteries was successfully evaluated in 20 patients
      (58 coronary arteries, 21 culprit lesions) by coronary angioscopy. The diameter
      stenosis (DS) of the culprit lesions and the maximal diameter stenosis (maxDS) of
      nonculprit segments were angiographically measured for each coronary artery.
      RESULTS: The DS of the culprit lesions and maxDS were 27 +/- 17% and 19 +/- 13%,
      respectively. Yellow plaques and thrombus were detected in 19 (90%) and 17 (81%)
      of 21 culprit lesions, respectively. Yellow plaques were equally prevalent in the
      infarct-related and non-infarct-related coronary arteries (3.7 +/- 1.6 vs. 3.4 +/
      1.8 plaques/artery). However, thrombus was only detected in the nonculprit
      segments of one (2%) coronary artery. CONCLUSIONS: In patients with MI, all three
      major coronary arteries are widely diseased and have multiple yellow though
      nondisrupted plaques. Acute MI may represent the pan-coronary process of
      vulnerable plaque development.

PMID- 11300437
TI  - Randomized trial of a noninvasive strategy to reduce hospital stay for patients
      with low-risk myocardial infarction.
AB  - OBJECTIVES: This study evaluated the feasibility, pertinence and psychosocial
      repercussions of a noninvasive reduced hospital stay strategy (three days) for
      low-risk patients with acute myocardial infarction using simple clinical criteria
      and predischarge 24-h ambulatory ST-segment ischemic monitoring. BACKGROUND:
      Previous studies evaluating shorter stays for uncomplicated myocardial infarction
      have been limited by retrospective or nonrandomized design and overdependence on
      invasive cardiac procedures. METHODS: One-hundred twenty consecutive patients
      admitted with an acute myocardial infarction fulfilling low-risk criteria were
      randomized 2:1 to a short hospital stay (80 patients) or standard stay (40
      patients). Short-stay patients with no ischemia on ST-segment monitoring were
      discharged on day 3, returning for exercise testing a week later. All analyses
      were on an intention-to-treat basis. RESULTS: Forty-one percent of all screened
      patients with acute myocardial infarction would have been medically eligible for
      the short-stay strategy. Seventeen patients (21%) were not discharged early
      because of ischemia on ST-monitoring or angina. Median initial hospital stay was
      halved from 6.9 days in the standard stay to 3.5 days in the short-stay group. At
      six months, median total days hospitalized were 7.5 in the standard stay and 3.6
      in the short-stay group (p < 0.0001). Adverse events and readmissions were low
      and not significantly different, and there were 25% fewer invasive cardiac
      procedures in the short-stay group. Psychosocial outcomes, risk factor changes
      and exercise test results were similar in the two groups. CONCLUSIONS: This
      reduced hospital stay strategy for low-risk patients with acute myocardial
      infarction is feasible and worthwhile, resulting in a substantial and sustained
      reduction in days hospitalized. It is without unfavorable psychosocial
      consequences, appears safe and does not increase the number of invasive cardiac
      procedures.

PMID- 11300438
TI  - Risk of acute first myocardial infarction and use of nicotine patches in a
      general population.
AB  - OBJECTIVES: To determine if nicotine patches, both as prescribed and used over
      the-counter, increase the risk of first myocardial infarction (MI). BACKGROUND:
      Although nicotine patches improve smoking cessation rates, case reports have
      raised the hypothesis that they may increase the risk of MI. METHODS: A
      population-based case-control study among 68 hospitals in an eight-county region
      surrounding Philadelphia was performed to determine if nicotine patches increase
      the risk of first MI. Cases were smokers (current or within the prior year)
      admitted to all hospitals in the region with a first MI. Controls were smokers
      (current or within the prior year) without prior MI selected from the same region
      using random-digit dialing. Data were collected by telephone interviews and chart
      reviews. The study had 80% power to detect an odds ratio (OR) of 2.5. RESULTS: A
      total of 653 cases and 2,990 controls were interviewed. There was no association
      between nicotine patches and MI (OR 0.46; 95% CI: 0.09, 1.47), and the confidence
      interval (CI) excluded an effect from nicotine patches equal to that from
      cigarette smoking itself (OR < 2.5). Among those who abstained from smoking, the
      OR for use of nicotine patches was 0.25 (95% CI: 0.01, 1.67); among those who
      smoked concomitantly, the OR for patch use was 0.83 (95% CI: 0.09, 3.81).
      Adjustment for confounding did not alter the study's findings (OR adjusted for
      confounders that could mask a harmful effect of patches: 0.70; 95% CI: 0.20,
      2.46). CONCLUSIONS: Nicotine patches, as used in actual practice, do not appear
      to be associated with an increased risk of MI.

PMID- 11300439
TI  - Real-time three-dimensional dobutamine stress echocardiography in assessment
      stress echocardiography in assessment of ischemia: comparison with two
      dimensional dobutamine stress echocardiography.
AB  - OBJECTIVES: This study was designed to test the feasibility and efficacy of using
      real-time three-dimensional echocardiography (RT-3D) to detect ischemia during
      dobutamine-induced stress (DSE) and compares the results with conventional two
      dimensional echocardiography (2D). BACKGROUND: Real-time three-dimensional
      echocardiography, a novel imaging technique, offers rapid acquisition with
      multiple simultaneous views of the left ventricle (LV). These features make it
      attractive for application during stress. METHODS: Of 279 consecutive patients
      screened for image quality by 2D, 253 patients with adequate images underwent RT
      3D and 2D within 30 s of each other at baseline and at peak DSE. RESULTS: Real
      time three-dimensional echocardiography and 2D showed good concordance in
      detection of abnormal LV wall motion at baseline (84%: Kappa = 0.59) and at peak
      DSE (88.9%: Kappa = 0.72). Left ventricular wall motion scores were similar at
      baseline and peak DSE using both techniques. Interobserver agreements for
      detection of ischemia at peak DSE were superior for RT-3D, 92.7% compared with
      84.6% for 2D (p < 0.05). Mean scanning time at peak stress by RT-3D in 50
      randomly selected patients was shorter, 27.4 +/- 10.7 s compared with 62.4 +/-
      20.1 s by 2D (p < 0.0001). In 90 patients with coronary angiograms, RT-3D had a
      sensitivity of 87.9% in the detection of coronary artery disease (CAD) compared
      with 79.3% by 2D. CONCLUSIONS: Real-time three-dimensional dobutamine stress
      echocardiography is feasible and sensitive in the detection of CAD. The procedure
      offers shorter scanning time, superior interobserver agreements and unique new
      views of the LV.

PMID- 11300440
TI  - Physiologic assessment of coronary artery stenosis by coronary flow reserve
      measurements with transthoracic Doppler echocardiography: comparison with
      exercise thallium-201 single piston emission computed tomography.
AB  - OBJECTIVES: We evaluated the value of coronary flow reserve (CFR), as determined
      by transthoracic Doppler echocardiography (TTDE), for physiologic assessment of
      coronary artery stenosis severity, and we compared TTDE measurements with those
      obtained by exercise thallium-201 (Tl-201) single-photon emission computed
      tomography (SPECT). BACKGROUND: Coronary flow reserve measurements by TTDE have
      been reported to be useful for assessing angiographic left anterior descending
      coronary artery (LAD) stenosis. However, discrepancies exist between angiographic
      and physiologic estimates of coronary lesion severity. METHODS: We studied 36
      patients suspected of having coronary artery disease. The flow velocity in the
      distal LAD was measured by TTDE both at rest and during intravenous infusion of
      adenosine. Coronary flow reserve was calculated as the ratio of hyperemic to
      basal peak (peak CFR) and mean (mean CFR) diastolic flow velocities. The CFR
      measurements by TTDE were compared with the results of Tl-201-SPECT. RESULTS:
      Complete TTDE data were acquired for 33 of 36 study patients. Of these 33
      patients, Tl-201-SPECT confirmed reversible perfusion defects in the LAD
      territories in 12 patients (group A). Twenty-one patients had normal perfusion in
      the LAD territories (group B). Peak CFR and mean CFR (mean value +/- SD) were 1.5
      +/- 0.6 and 1.5 +/- 0.7 in group A and 2.8 +/- 0.8 and 2.7 +/- 0.7 in group B,
      respectively. Both peak and mean CFR < or = 2.0 predicted reversible perfusion
      defects, with a sensitivity and specificity of 92% and 90%, respectively.
      CONCLUSIONS: Noninvasive measurement of CFR by TTDE provides data equivalent to
      those obtained by Tl-201-SPECT for physiologic estimation of the severity of LAD
      stenosis.

PMID- 11300441
TI  - Fractional flow reserve, absolute and relative coronary blood flow velocity
      reserve in relation to the results of technetium-99m sestamibi single-photon
      emission computed tomography in patients with two-vessel coronary artery disease.
AB  - OBJECTIVES: We sought to perform a direct comparison between perfusion
      scintigraphic results and intracoronary-derived hemodynamic variables (fractional
      flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR
      and rCFVR, respectively]) in patients with two-vessel disease. BACKGROUND: There
      is limited information on the diagnostic accuracy of intracoronary-derived
      variables (CFVR, FFR and rCFVR) in patients with multivessel disease. METHODS:
      Dipyridamole technetium-99m sestamibi (MIBI) single-photon emission computed
      tomography (SPECT) was performed in 127 patients. The presence of reversible
      perfusion defects in the region of interest was determined. Within one week,
      angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary
      lesions after intracoronary administration of adenosine. The predictive value for
      the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR
      was evaluated by the area under the curve (AUC) of the receiver operating
      characteristics curves. RESULTS: The mean percentage diameter stenosis was 57%
      (range 35% to 85%), as measured by quantitative coronary angiography. Using per
      patient analysis, the AUCs for CFVR (0.70 +/- 0.052), rCFVR (0.72 +/- 0.051) and
      FFR (0.76 +/- 0.050) were not significantly different (p = NS). The percentages
      of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR
      and FFR, respectively. Per-lesion analysis, using all 161 measured lesions,
      yielded similar results. CONCLUSIONS: The diagnostic accuracy of three
      intracoronary-derived hemodynamic variables, as compared with the results of
      perfusion scintigraphy, is similar in patients with two-vessel coronary artery
      disease. Cut-offvalues of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be
      used for clinical decision-making in this patient cohort. Discordant results were
      obtained in 23% of the cases that require prospective evaluation for appropriate
      patient management.

PMID- 11300442
TI  - Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients
      undergoing coronary stenting.
AB  - OBJECTIVES: We sought to investigate whether abciximab, tirofiban and
      eptifibatide achieve comparable antiplatelet effects with coronary stenting.
      BACKGROUND: The glycoprotein (GP) IIb/IIIa antagonists abciximab, tirofiban and
      eptifibatide differ in chemical structure, binding site and pharmacokinetics.
      METHODS: Sixty patients undergoing coronary stenting were randomly assigned to
      abciximab (bolus 0.25 mg/kg body weight, infusion 10 microg per min for 12 h),
      tirofiban (bolus 10 microg/kg, infusion 0.15 microg/kg per min for 72 h) or
      eptifibatide (bolus 180 microg/kg, infusion 2 microg/kg per min for 72 h). We
      took serial blood samples to analyze platelet function by using flow cytometry,
      turbidimetric aggregometry and the rapid platelet-function assay (RPFA). RESULTS:
      As assessed by RPFA, platelet aggregation after 2 h of infusion was reduced to
      5.9 +/- 7.8% (mean +/- SD) of baseline by abciximab, to 5.0 +/- 5.4% by tirofiban
      and to 7.8 +/- 7.1% by eptifibatide (p = 0.42). Turbidimetric aggregometry with
      adenosine diphosphate stimulation yielded similar results, whereas percent
      inhibition of platelet aggregation after thrombin receptor stimulation was 45.8
      +/- 16.8% with abciximab, 51.3 +/- 17.6% with tirofiban and 52.9 +/- 14.8% with
      eptifibatide (p = 0.37). Tirofiban and eptifibatide maintained their level of
      platelet inhibition during infusion. Flow cytometry revealed that the reduction
      in the monocyte-platelet interaction by abciximab, tirofiban and eptifibatide was
      not significantly different (20.0 +/- 21.9%, 23.8 +/- 18.2% and 21.0 +/- 19.8%,
      respectively; p = 0.87). CONCLUSIONS: Abciximab, tirofiban and eptifibatide, at
      currently recommended doses, achieved similar levels of inhibition of platelet
      aggregation and a similar reduction in the platelet-monocyte interaction.

PMID- 11300443
TI  - Long-term vessel response to a self-expanding coronary stent: a serial volumetric
      intravascular ultrasound analysis from the ASSURE Trial.A Stent vs. Stent
      Ultrasound Remodeling Evaluation.
AB  - OBJECTIVES: We sought to investigate the in vivo mechanical properties of a new
      self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel
      response over time. BACKGROUND: Preclinical studies have suggested that self
      expanding stents may produce less vessel wall injury at initial deployment,
      leading to larger follow-up lumens than with balloon-expandable stents. However,
      the influence of the chronic stimulus from self-expanding stents on the vessel
      wall remains unknown. METHODS: Sixty-two patients were randomly assigned to
      either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz
      balloon-expandable stent group (n = 30). Intravascular ultrasound was performed
      after stent deployment and at six-month follow-up. RESULTS: At follow-up, the
      RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz
      stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/-
      1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant
      difference in net late lumen loss was observed between the two groups. On the
      other hand, analysis at the peristent margins demonstrated that mean late loss
      was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz
      group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS: Serial
      volumetric IVUS revealed that the RADIUS stents continued to enlarge during the
      follow-up period. In this stent implantation protocol, this expansion was
      accompanied by a greater amount of neointima than the Palmaz-Schatz stents,
      resulting in similar late lumen loss in both configurations. In the peristent
      margins, however, late lumen loss was minimized with the RADIUS stents.

PMID- 11300444
TI  - Treatment of no-reflow and impaired flow with the nitric oxide donor
      nitroprusside following percutaneous coronary interventions: initial human
      clinical experience.
AB  - OBJECTIVES: The objective of this study was to test the hypothesis that the
      intracoronary administration of a direct donor of nitric oxide is a safe and
      effective method to treat impaired blood flow (no-reflow phenomenon) that occurs
      during percutaneous transluminal coronary interventions (PTCI). BACKGROUND: The
      absence of blood flow or decreased blood flow in a coronary artery following PTCI
      despite the presence of a patent epicardial vessel or graft is designated "no
      reflow" or "impaired flow." This alteration in blood flow is a serious
      complication of percutaneous revascularization strategies that results in an
      increased incidence of morbidity, myocardial infarction and mortality. METHODS:
      Nineteen consecutive patients undergoing standard percutaneous revascularization
      procedures complicated by either no-reflow or impaired flow that received
      intracoronary nitroprusside treatment were studied. One patient had two
      procedures performed on two separate grafts on two successive days. Interventions
      were performed on either saphenous vein grafts or native vessels and utilized
      angioplasty, stent deployment or rotational atherectomy strategies. Following
      interventions that were associated with impaired flow, varying total doses (of
      nitroprusside 50 to 1,000 microg) were administered into the coronary artery or
      saphenous vein graft. The angiographic archives before and after intracoronary
      administration of nitroprusside were analyzed for TIMI grade flow and a frame
      count method was used to quantitate blood flow velocity. RESULTS: Following a
      PTCI that resulted in either no-reflow or impaired flow, nitroprusside (median
      dose 200 microg) was found to lead to a highly significant and rapid improvement
      in both angiographic flow (p < 0.01 compared with pretreatment angiogram) and
      blood flow velocity (p < 0.01 compared with pretreatment angiogram). No
      significant hypotension or other adverse clinical events were associated with
      nitroprusside administration. CONCLUSIONS: The direct nitric oxide donor
      nitroprusside is an effective, safe treatment of impaired blood flow and no
      reflow associated with PTCI. The use of nitroprusside to treat syndromes
      secondary to microvascular dysfunction may provide a novel therapeutic strategy
      for treating no-reflow or impaired blood flow following percutaneous
      interventions.

PMID- 11300445
TI  - Improved endothelial function with metformin in type 2 diabetes mellitus.
AB  - OBJECTIVES: This study was designed to assess the effect of metformin on impaired
      endothelial function in type 2 diabetes mellitus. BACKGROUND: Abnormalities in
      vascular endothelial function are well recognized among patients with type 2
      (insulin-resistant) diabetes mellitus. Insulin resistance itself may be central
      to the pathogenesis of endothelial dysfunction. The effects of metformin, an
      antidiabetic agent that improves insulin sensitivity, on endothelial function
      have not been reported. METHODS: Subjects with diet-treated type 2 diabetes but
      without the confounding collection of cardiovascular risk factors seen in the
      metabolic syndrome were treated with metformin 500 mg twice daily (n = 29) or
      placebo (n = 15) for 12 weeks. Before and after treatment, blood flow responses
      to intraarterial administration of endothelium-dependent (acetylcholine),
      endothelium-independent (sodium nitroprusside) and nitrate-independent
      (verapamil) vasodilators were measured using forearm plethysmography. Whole-body
      insulin resistance was assessed on both occasions using the homeostasis model
      (HOMA-IR). RESULTS: Subjects who received metformin demonstrated statistically
      significant improvement in acetylcholine-stimulated flows compared with those
      treated with placebo (p = 0.0027 by 2-way analysis of variance), whereas no
      significant effect was seen on nitroprusside-stimulated (p = 0.27) or verapamil
      stimulated (p = 0.40) flows. There was a significant improvement in insulin
      resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise
      multivariate analysis insulin resistance was the sole predictor of endothelium
      dependent blood flow following treatment (r = -0.659, p = 0.0012). CONCLUSIONS:
      Metformin treatment improved both insulin resistance and endothelial function,
      with a strong statistical link between these variables. This supports the concept
      of the central role of insulin resistance in the pathogenesis of endothelial
      dysfunction in type 2 diabetes mellitus. This has important implications for the
      investigation and treatment of vascular disease in patients with type 2 diabetes
      mellitus.

PMID- 11300446
TI  - Rapid improvement of nitric oxide bioavailability after lipid-lowering therapy
      with cerivastatin within two weeks.
AB  - OBJECTIVES: We investigated whether improvement of endothelial dysfunction in
      hypercholesterolemia can be achieved with short-term lipid-lowering therapy.
      BACKGROUND: Impaired endothelium-dependent vasodilation plays a pivotal role in
      the pathogenesis of atherosclerosis and acute coronary syndromes. METHODS: In a
      randomized, double-blind, placebo-controlled trial, we studied 37 patients (52 +/
      11 yrs) with low density lipoprotein cholesterol > or = 160 mg/dl (196 +/- 44
      mg/dl) randomly assigned to either cerivastatin (0.4 mg/d) or placebo.
      Endothelium-dependent vasodilation of the forearm vasculature was measured by
      plethysmography and intra-arterial infusion of acetylcholine (ACh 12, 48
      microg/min) and endothelium-independent vasodilation by intra-arterial infusion
      of nitroprusside (3.2, 12.8 microg/min). RESULTS: Low density lipoprotein
      cholesterol decreased after two weeks of treatment (cerivastatin -33 +/- 4% vs.
      placebo + 2 +/- 4%, x +/- SEM, p < 0.001). Endothelium-dependent vasodilation
      improved after two weeks of therapy with cerivastatin compared with baseline (ACh
      12 microg/min: + 22.3 +/- 5.2 vs. + 11.2 +/- 1.9 ml/min/100 ml, p < 0.01; ACh 48
      microg/min: +31.2 +/- 6.3 vs. +19.1 +/- 3.1 ml/min/100 ml, p < 0.05). In
      contrast, changes in forearm blood flow to ACh were similar before and after
      therapy in the placebo group (ACh 12 microg/min: + 12.9 +/- 3.6 vs. + 9.0 +/- 1.9
      ml/min/100 ml, NS; ACh 48 microg/min: +20.7 +/- 3.7 vs. 19.4 +/- 2.9 ml/min/100
      ml, NS). Endothelium-dependent vasodilation improved in comparison with placebo
      (ACh 48 microg/min: +203 +/- 85% [cerivastatin] vs. -26 +/- 71% [placebo], p <
      0.05). This improvement in endothelium-dependent vasodilation was no longer
      observed when the nitric oxide-synthase inhibitor N(G)-monomethyl-L-arginine was
      coinfused (ACh 48 microg/min + N(G)-monomethyl-L-arginine 4 micromol/min -48 +/-
      85% [cerivastatin]). CONCLUSIONS: Short-term lipid-lowering therapy with
      cerivastatin can improve endothelial function and NO bioavailability after two
      weeks in patients with hypercholesterolemia.

PMID- 11300447
TI  - Effects of mental stress on coronary epicardial vasomotion and flow velocity in
      coronary artery disease: relationship with hemodynamic stress responses.
AB  - OBJECTIVES: This study examines the prevalence and hemodynamic determinants of
      mental stress-induced coronary vasoconstriction in patients undergoing diagnostic
      coronary angiography. BACKGROUND: Decreased myocardial supply is involved in
      myocardial ischemia triggered by mental stress, but the determinants of stress
      induced coronary constriction and flow velocity responses are not well
      understood. METHODS: Coronary vasomotion was assessed in 76 patients (average age
      59.9 +/- 10.4 years; eight women). Coronary flow velocity responses were assessed
      in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms
      were obtained after a baseline control period, a 3-min mental arithmetic task and
      administration of 200 microg intracoronary nitroglycerin. Arterial blood pressure
      (BP) and heart rate assessments were made throughout the procedure. RESULTS:
      Mental stress resulted in significant BP and heart rate increases (p < 0.001).
      Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary
      artery disease (CAD) (18.6%). Higher mental stress pressor responses were
      associated with more constriction in diseased segments (rdeltaSBP = -0.26,
      rdeltaDBP = -0.30, rdeltaMAP = -0.29; p's < 0.05) but not with responses in
      nonstenotic segments. The overall constriction of diseased segments was not
      significant (p > 0.10), whereas a small but significant constriction occurred in
      nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients
      without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns).
      Cardiovascular risk factors were not predictive of stress-induced vasomotion in
      patients with CAD. CONCLUSIONS: Coronary vasoconstriction in angiographically
      diseased arteries varies with hemodynamic responses to mental arousal. Coronary
      flow responses are attenuated in CAD patients. Thus, combined increases in
      cardiac demand and concomitant reduced myocardial blood supply may contribute to
      myocardial ischemia with mental stress.

PMID- 11300448
TI  - Attenuation of endothelin-1 induced vasoconstriction by 17beta estradiol is not
      sustained during long-term therapy in postmenopausal women with coronary heart
      disease.
AB  - OBJECTIVES: The goal of this study was to determine the long-term effects of
      estrogen replacement therapy on the response to endothelin-1 (ET-1) in
      postmenopausal women with coronary heart disease. BACKGROUND: It is thought that
      the vasoconstrictor ET-1 is involved in the development and progression of
      atherosclerosis. Estrogen replacement may slow the development of atherosclerosis
      in postmenopausal women. METHODS: Nineteen of 20 postmenopausal women randomized
      to either three months of 2 mg oral estradiol or placebo completed the double
      blind placebo-controlled protocol. Change in forearm blood flow (FBF) in response
      to a 60 min brachial arterial infusion of ET-1 (5 pmol/min) was measured before
      randomization, after one month of randomized therapy and after three months of
      therapy using venous occlusion plethysmography. RESULTS: Estrogen treatment had
      no effect on baseline FBF. Systolic and diastolic blood pressure and heart rate
      did not change in response to estrogen therapy or ET-1. Before randomization, in
      response to ET-1, FBF was reduced by -21.9% (mean response over 60 min) in the
      placebo group and -19.0% in the estradiol group (p = 0.67). After one month of
      therapy, the response was attenuated in the estrogen group, -10.0%, compared with
      the placebo group, -23.6 (difference in means 13.6%, 95% confidence interval
      [0.7%, 26.6%], p = 0.041). After three months of therapy, there was no difference
      in response between the placebo group, -27.0%, and estrogen group, -30.2% (p =
      0.65). CONCLUSIONS: In postmenopausal women with coronary heart disease, estrogen
      therapy inhibits the vasoconstrictor response to ET-1 after one month of therapy.
      This effect is lost after three months of therapy, suggesting that tachyphylaxis
      to one potentially beneficial action of estradiol develops during chronic
      treatment.

PMID- 11300449
TI  - Comparative effects of aging in men and women on the properties of the arterial
      tree.
AB  - OBJECTIVES: We measured the properties of the arterial tree, seeking differences
      between men and women as they aged. BACKGROUND: There are many differences
      between men and women, besides menopause, which might account for such
      disparities. These include body height, heart rate, stroke volume and smaller
      arterial diameters. Any gender differences in arterial stiffness could influence
      pulse pressure (PP), now recognized as a cardiovascular risk factor. METHODS: A
      total of 530 patients (347 men and 183 women) were classified by age into
      quartiles: < or = 40, 41-47, 48-54 and > or = 55 years. The middle groups
      represented the menopausal years. Studies included brachial artery blood pressure
      (BP), aortic pulse wave velocity (PWV), B-mode ultrasonography and wave form
      analysis of the common carotid artery (CCA), with its conversion to the aortic
      wave formin. Standard echocardiography provided left ventricular dimensions and
      flows. Calculated values included CCA compliance and distensibility, systemic
      compliance, stroke volume and peripheral resistance. RESULTS: At all ages, women
      had higher heart rates but lower BP than men. Pulse pressure, however, was lower
      in young women and higher in older women. Measurements influenced by body size,
      such as CCA diameter, compliance and systemic compliance, were lower in women.
      Those related to arterial wall properties, such as CCA and aortic distensibility,
      were the same. Although aortic PWV rose similarly with aging, PWV had more of an
      influence on PP in women than did mean BP. The reverse was true in men.
      CONCLUSIONS: Despite lower mean BP and similar arterial distensibilitvy, women
      develop a higher degree of pulsatility with aging, as compared with men. This is
      mainly due to their smaller physical characteristics, independent of the role of
      menopause and its related hormonal changes.

PMID- 11300450
TI  - Intermittent claudication: an objective office-based assessment.
AB  - OBJECTIVES: We sought to compare standard lower extremity vascular laboratory
      treadmill exercise with the office-based active pedal plantarflexion technique.
      BACKGROUND: Intermittent claudication is relatively common in elderly patients
      and is an important predictor of cardiovascular morbidity and mortality.
      Noninvasive testing using resting and posttreadmill exercise ankle:brachial
      systolic blood pressure indices is often required to confirm the diagnosis and
      objectively assess the severity of lower extremity arterial occlusive disease.
      This is traditionally performed in a formal vascular laboratory setting. METHODS:
      Fifty consecutive patients (100 lower extremities) with known or suspected
      intermittent claudication referred for lower extremity treadmill exercise testing
      were also tested with active pedal plantarflexion using a prospective, randomized
      crossover design. Supine ankle:brachial systolic blood pressure indices were
      measured immediately before and after each form of exercise. RESULTS: There was
      an excellent correlation (r = 0.95, 95% confidence interval 0.93 to 0.97) between
      mean postexercise ankle:brachial systolic blood pressure indices for treadmill
      exercise and active pedal plantarflexion. There was no significant difference in
      outcome based on the order of testing or the severity of arterial occlusive
      disease. Symptoms of angina or dyspnea occurred in 11 patients (22%) with
      treadmill exercise versus zero patients with active pedal plantarflexion.
      CONCLUSIONS: Active pedal plantarflexion is an office-based test that compares
      favorably with treadmill exercise for the noninvasive, safe, objective and
      economical assessment of lower extremity arterial occlusive disease.

PMID- 11300451
TI  - The N + 1 difference: a new measure for entrainment mapping.
AB  - OBJECTIVES: The purpose of this study was to develop and test a new entrainment
      mapping measurement, the N + 1 difference. BACKGROUND: Entrainment mapping is
      useful for identifying re-entry circuit sites but is often limited by difficulty
      in assessing: 1) changes in QRS complexes or P-waves that indicate fusion, and 2)
      the postpacing interval (PPI) recorded directly from the stimulation site.
      METHODS: In computer simulations of re-entry circuits, the interval from a
      stimulus that reset tachycardia to a timing reference during the second beat
      after the stimulus was compared with the timing of local activation at the site
      during tachycardia to define an interval designated the N + 1 difference. The N +
      1 difference was compared with the PPI-tachycardia cycle length (TCL) difference
      in simulations and at 65 sites in 10 consecutive patients with ventricular
      tachycardia (VT) after myocardial infarction and at 45 sites in 10 consecutive
      patients with atrial flutter. RESULTS: In simulations, the N + 1 difference was
      equal to the PPI-TCL difference. During mapping of VT and atrial flutter, the N +
      1 difference correlated well with the PPI-TCL difference (r > or = 0.91, p <
      0.0001), identifying re-entry circuit sites with sensitivity of > or = 86% and
      specificity of > or = 90%. Accuracy was similar using either the surface
      electrocardiogram or an intracardiac electrogram (Eg) as the timing reference.
      CONCLUSIONS: The N + 1 difference allows entrainment mapping to be used to
      identify re-entry circuit sites when it is difficult to evaluate Egs at the
      mapping site or fusion in the surface electrocardiogram.

PMID- 11300452
TI  - Prediction of sudden cardiac death by fractal analysis of heart rate variability
      in elderly subjects.
AB  - OBJECTIVES: The aim of this study was to test the hypothesis that abnormal
      scaling characteristics of heart rate (HR) predict sudden cardiac death in a
      random population of elderly subjects. BACKGROUND: An abnormality in the short
      term fractal scaling properties of HR has been observed to be related to a risk
      of life-threatening arrhythmias among patients with advanced heart diseases. The
      predictive power of altered short-term scaling properties of HR in general
      populations is unknown. METHODS: A random sample of 325 subjects, age 65 years or
      older, who had a comprehensive risk profiling from clinical evaluation,
      laboratory tests and 24-h Holter recordings were followed up for 10 years. Heart
      rate dynamics, including conventional and fractal scaling measures of HR
      variability, were analyzed. RESULTS: At 10 years of follow-up, 164 subjects had
      died. Seventy-one subjects had died of a cardiac cause, and 29 deaths were
      defined as sudden cardiac deaths. By univariate analysis, a reduced short-term
      fractal scaling exponent predicted the occurrence of cardiac death (relative risk
      [RR] 2.5, 95% confidence interval [CI], 1.9 to 3.2, p < 0.001) and provided even
      stronger prediction of sudden cardiac death (RR 4.1, 95% CI, 2.5 to 6.6, p <
      0.001). After adjusting for other predictive variables in a multivariate
      analysis, reduced exponent value remained as an independent predictor of sudden
      cardiac death (RR 4.3, 95% CI, 2.0 to 9.2, p < 0.001). CONCLUSIONS: Altered short
      term fractal scaling properties of HR indicate an increased risk for cardiac
      mortality, particularly sudden cardiac death, in the random population of elderly
      subjects.

PMID- 11300453
TI  - Increased dispersion and shortened refractoriness caused by verapamil in chronic
      atrial fibrillation.
AB  - OBJECTIVES: The objective was to assess the effect ofverapamil on atrial
      fibrillation (AF) cycle length and spatial dispersion of refractoriness in
      patients with chronic AF. BACKGROUND: Previous studies have suggested that
      verapamil prevents acute remodeling by AF. The effects of verapamil in chronic AF
      are unknown. METHODS: During electrophysiologic study in 15 patients with chronic
      AF (duration >1 year), 12 unipolar electrograms were recorded from right atrial
      free wall, right atrial appendage and coronary sinus, along with monophasic
      action potential recordings from the right atrial appendage. The mean
      fibrillatory interval at each atrial recording site was used as an index for
      local refractoriness. Dispersion of refractoriness was calculated as the standard
      deviation of all local mean fibrillatory intervals expressed as a percentage of
      the overall mean fibrillatory interval. After baseline measurements, verapamil
      (0.075 mg/kg intravenous in 10 min) was infused and the measurements were
      repeated. RESULTS: After administration ofverapamil, mean fibrillatory intervals
      shortened by a mean of 16.6 +/- 3.3 ms (p < 0.001) at the right free wall, 15.0
      +/- 3.5 ms (p < 0.001) at the appendage and 17.1 +/- 3.2 ms (p < 0.01) in the
      coronary sinus. Monophasic action potential duration decreased by 15.9 +/- 4.0 ms
      (p < 0.01). Dispersion of refractoriness increased in all patients from 3.8 +/-
      0.8 to 5.1 +/- 1.8 (p < 0.001). A strong correlation between mean fibrillatory
      intervals and action potential duration was found, both before and after
      verapamil. CONCLUSIONS: Verapamil caused shortening of refractoriness and
      increase in spatial dispersion of refractoriness in patients with chronic AF.
      This implies that verapamil is not useful in reversing the remodeling process in
      these patients.

PMID- 11300454
TI  - Ventricular tachycardias arising from the aortic sinus of valsalva: an under
      recognized variant of left outflow tract ventricular tachycardia.
AB  - OBJECTIVES: To describe a normal heart left bundle branch block, inferior axis
      ventricular tachycardia (VT), that could not be ablated from the right or left
      ventricular outflow tracts. BACKGROUND: Whether these VTs are epicardial and can
      be identified by a specific electrocardiographic pattern is unclear. METHODS:
      Twelve patients with normal heart left bundle branch block, inferior axis VT and
      previously failed ablation were included in this study. Together with mapping in
      the right and left ventricular outflow tracts, we obtained percutaneous
      epicardial mapping in the first five patients and performed aortic sinus of
      Valsalva mapping in all patients. RESULTS: No adequate pace mapping was observed
      in the right and left ventricular outflow tracts. Earliest ventricular activation
      was noted in the epicardium and the aortic cusps. All patients were successfully
      ablated from the aortic sinuses of Valsalva (95% CI 0% to 18%). The
      electrocardiographic pattern associated with this VT was left bundle branch
      block, inferior axis and early precordial transition with Rs or R in V2 or V3.
      Ventricular tachycardia from the left sinus had rS pattern in lead I, and VT from
      the noncoronary sinus had a notched R wave in lead I. None of the patients had
      complications and all remained arrhythmia-free at a mean follow-up of 8 +/- 2.6
      months. CONCLUSIONS: Normal heart VT with left bundle branch block, inferior axis
      and early precordial transition can be ablated in the majority of patients from
      either the left or the noncoronary aortic sinus of Valsalva.

PMID- 11300455
TI  - Effects of verapamil and lidocaine on two components of the re-entry circuit of
      verapamil-senstitive idiopathic left ventricular tachycardia.
AB  - OBJECTIVES: We characterized pharmacologically the slow conduction zone of
      verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) with regard to
      the late diastolic potential (LDP). BACKGROUND: We showed that the slow
      conduction zone of ILVT could be divided into two components by LDP; that is, the
      distal component with a tachycardia-dependent conduction delay property and the
      proximal one without it. METHODS: Electrophysiologic studies were performed in
      eight consecutive patients. The LDP was recorded during left ventricular (LV)
      mapping during ILVT. Entrainment was performed from the right ventricular outflow
      tract while recording LDP. The effects of lidocaine (1 mg/kg body weight) and
      verapamil (0.5 or 1.0 mg) were examined during entrainment. RESULTS: The LDPs
      preceding the Purkinje potential (PP) were serially recorded from the upper third
      to the middle of the LV septum along the narrow longitudinal line. The
      ventricular tachycardia (VT) cycle length increased after lidocaine (p < 0.05),
      and further after verapamil (p < 0.05). The increments in the VT cycle length
      after administration of the drugs strongly correlated with those in LDP-PP (r >
      0.9 for both drugs). The interval from the ventricular potential to LDP was
      unchanged after administration of the drugs. In one patient, verapamil terminated
      VT by local conduction block between LDP and PP. The LDP-PP measured during
      entrainment increased after lidocaine, and further after verapamil, whereas the
      interval from the stimulus to LDP remained unchanged. CONCLUSIONS: The component
      distal to LDP is mainly calcium channel-dependent and partly depressed sodium
      channel-dependent. The proximal component is considered to be sodium channel
      dependent (normal).

PMID- 11300456
TI  - Detection of subclinical coronary atherosclerosis using two-dimensional, high
      resolution transthoracic echocardiography.
AB  - OBJECTIVES: We evaluated whether two-dimensional high-resolution transthoracic
      echocardiography (HR-2DTTE) can detect changes in arterial wall thickness and
      size associated with subclinical coronary artery disease (CAD). BACKGROUND:
      Arterial wall thickening, compensatory arterial enlargement and a preserved
      arterial lumen characterize subclinical atherosclerosis. Detection of these
      changes during the asymptomatic stage of CAD may allow early treatment and
      prevention of acute coronary events. METHODS: Twenty-six patients with
      angiographically proven CAD and 29 normal volunteers underwent HR-2DTTE
      evaluation of the left anterior descending coronary artery (LAD) using an ATL
      5000 echograph (Advanced Technology Laboratories, Bothell, Washington) with a 4
      to 7 MHz transducer. Significant (>70%) LAD stenosis was present in 15 patients
      (mean 82%); 11 patients did not have significant LAD stenosis (mean 26%) and
      represented a surrogate for subclinical LAD disease. Wall thickness, maximal
      luminal diameter and external diameter of the LAD were measured. RESULTS: Left
      anterior descending coronary artery wall thickness was larger in patients (1.9 +/
      0.4 mm) than it was in volunteers (0.9 +/- 0.1 mm, p < 0.001). The external
      diameter of the LAD was (6.0 +/- 1.1 mm) in patients and (3.9 +/- 0.7 mm) in
      volunteers (p < 0.001). Luminal diameter was 2.2 +/- 0.5 mm in patients and 2.1
      +/- 0.6 mm in volunteers (p = NS). There was no difference in wall thickness (1.9
      +/- 0.4 mm vs. 2.0 +/- 0.4 mm), luminal diameter (2.2 +/- 0.5 mm vs. 2.2 +/- 0.4
      mm) and external diameter (5.9 +/- 1.0 mm vs. 6.2 +/- 1.2 mm) between the
      patients with <70% and >70% LAD stenosis. CONCLUSIONS: Left anterior descending
      coronary artery wall thickness and external diameter are significantly increased
      in patients with CAD as compared with normal subjects, and HR-2DTTE is sensitive
      enough to detect these differences. Wall thickness and external diameter are
      increased to the same extent in patients with obstructive and subclinical LAD
      disease.

PMID- 11300457
TI  - Noninvasive detection and evaluation of atherosclerotic coronary plaques with
      multislice computed tomography.
AB  - OBJECTIVES: The aim of the present study was to evaluate the accuracy in
      determining coronary lesion configuration by multislice computed tomography
      (MSCT). The results were compared with the findings of intracoronary ultrasound
      (ICUS). BACKGROUND: The risk of acute coronary syndromes caused by plaque
      disruption and thrombosis depends on plaque composition rather than stenosis
      severity. Thus, the reliable noninvasive assessment of plaque configuration would
      constitute an important step forward for risk stratification in patients with
      known or suspected coronary artery disease. Just recently, MSCT scanners became
      available for general purpose scanning. Due to improved spatial and temporal
      resolution, this new technology holds promise to allow for differentiation of
      coronary lesion configuration. METHODS: The ICUS and MSCT scans (Somatom Volume
      Zoom, Siemens, Forchheim, Germany) were performed in 15 patients. Plaque
      composition was analyzed according to ICUS (plaque echogenity: soft,
      intermediate, calcified) and MSCT criteria (plaque density expressed by
      Hounsfield units [HU]). RESULTS: Thirty-four plaques were analyzed. With ICUS,
      the plaques were classified as soft (n = 12), intermediate (n = 5) and calcified
      (n = 17). Using MSCT, soft plaques had a density of 14 +/- 26 HU (range -42 to
      +47 HU), intermediate plaques of 91 +/- 21 HU (61 to 112 HU) and calcified
      plaques of 419 +/- 194 HU (126 to 736 HU). Nonparametric Kruskal-Wallis test
      revealed a significant difference of plaque density among the three groups (p <
      0.0001). CONCLUSIONS: Our results indicate that coronary lesion configuration
      might be correctly differentiated by MSCT. Since also rupture-prone soft plaques
      can be detected by MSCT, this noninvasive method might become an important
      diagnostic tool for risk stratification in the near future.

PMID- 11300458
TI  - Increased von Willebrand factor in the endocardium as a local predisposing factor
      for thrombogenesis in overloaded human atrial appendage.
AB  - OBJECTIVES: We investigated immunoreactive von Willebrand factor (vWF), a
      platelet adhesion molecule, in the endocardial endothelium and its relationship
      to thrombogenesis in the human atrial appendage. BACKGROUND: Intra-atrial
      thrombogenesis is generally thought to be induced by blood stasis in the atrial
      appendage involved with atrial fibrillation (AF). Little attention has been paid
      to alterations of the endocardial endothelium on which the thrombus develops.
      METHODS: Atrial appendage tissue was obtained at heart surgery or at autopsy from
      AF and non-AF cardiac patients and from noncardiac patients. Immunohistochemistry
      for endothelial cell markers including vWF, CD31, CD34 and endothelial nitric
      oxide synthase (eNOS) and platelet glycoprotein Ib/IX or IIb/IIIa was performed
      and semiquantitatively graded. RESULTS: In contrast to the apparent
      immunostaining for CD31, CD34 and eNOS, only focal or little immunoreactive vWF
      was seen in the endocardium of noncardiac patients. Immunoreactive vWF in the
      endocardial endothelium was increased in most cardiac patients, particularly in
      the left, but not in the right, atrial appendage of patients with mitral valvular
      disease, irrespective of whether AF was present. Platelet adhesion/thrombus
      formation in the endocardium was found in limited sites in which the overlying
      endothelium was deficient in eNOS and CD34. When warfarin-treated cases were
      excluded, there was a significant correlation between the immunohistochemical
      grade for vWF and the degree of platelet adhesion/thrombus formation in the
      endocardium. CONCLUSIONS: Immunoreactive vWF in the endocardial endothelium was
      increased in overloaded human atrial appendage, which may be a local predisposing
      factor for intraatrial thrombogenesis.

PMID- 11300459
TI  - Activation of the cardiac renin-angiotensin system and increased myocardial
      collagen expression in human aortic valve disease.
AB  - OBJECTIVES: We sought to determine whether the cardiac renin-angiotensin system
      (RAS) is activated in human aortic valve disease depending on left ventricular
      function, and we analyzed the concomitant regulation of the extracellular matrix
      components. BACKGROUND: In animal models with pressure or volume load, activation
      of the cardiac RAS increases fibrosis. In human aortic valve disease, the
      ventricular collagen protein content is increased, but only scarce data on the
      activation state of the cardiac RAS and its effects on collagen and fibronectin
      messenger ribonucleic acid (mRNA) are available. METHODS: In left ventricular
      biopsies from patients with aortic valve stenosis (AS) and aortic valve
      regurgitation and from control subjects, we quantitated mRNAs for angiotensin
      converting enzyme (ACE), chymase, transforming growth factor-beta1 (TGF-beta1),
      collagen I, collagen III and fibronectin by reverse-transcription polymerase
      chain reaction. Proteins were localized by immunohistochemistry; ACE activity was
      determined by high performance liquid chromatography; and TGF-beta protein by
      quantitative enzyme immunoassay. RESULTS: Protein, ACE and TGF-beta1 mRNA were
      significantly increased in patients with AS and AR (1.5- to 2.1-fold) and
      correlated with each other. The increase occurred also in patients with normal
      systolic function. Collagen I and III and fibronectin mRNAs were both upregulated
      about twofold in patients with AS and AR. In AS, collagen and fibronectin mRNA
      expression levels were positively correlated with left ventricular end-diastolic
      pressure and inversely with left ventricular ejection fraction (LVEF).
      CONCLUSIONS: In human hearts, pressure and volume overload increases cardiac ACE
      and TGF-beta1 in the early stages. This activation of the cardiac RAS may
      contribute to the observed increase in collagen I and III and fibronectin mRNA
      expression. The increase in extracellular matrix already exists in patients with
      a normal LVEF, and it increases with functional impairment.

PMID- 11300460
TI  - Assessment of aortic regurgitation by transesophageal color Doppler imaging of
      the vena contracta: validation against an intraoperative aortic flow probe.
AB  - OBJECTIVES: This study was performed to validate the accuracy of color flow vena
      contracta (VC) measurements of aortic regurgitation (AR) severity by comparing
      them to simultaneous intraoperative flow probe measurements of regurgitant
      fraction (RgF) and regurgitant volume (RgV). BACKGROUND: Color Doppler imaging of
      the vena contracta has emerged as a simple and reliable measure of the severity
      of valvular regurgitation. This study evaluated the accuracy of VC imaging of AR
      by transesophageal echocardiography (TEE). METHODS: A transit-time flow probe was
      placed on the ascending aorta during cardiac surgery in 24 patients with AR. The
      flow probe was used to measure RgF and RgV simultaneously during VC imaging by
      TEE. Flow probe and VC imaging were interpreted separately and in blinded
      fashion. RESULTS: A good correlation was found between VC width and RgF (r =
      0.85) and RgV (r = 0.79). All six patients with VC width >6 mm had a RgF >0.50.
      All 18 patients with VC width <5 mm had a RgF <0.50. Vena contracta area also
      correlated well with both RgF (r = 0.81) and RgV (r = 0.84). All six patients
      with VC area >7.5 mm2 had a RgF >0.50, and all 18 patients with a VC area <7.5
      mm2 had a RgF <0.50. In a subset of nine patients who underwent afterload
      manipulation to increase diastolic blood pressure, RgV increased significantly
      (34 +/- 26 ml to 41 +/- 27 ml, p = 0.042) while VC width remained unchanged (5.4
      +/- 2.8 mm to 5.4 +/- 2.8 mm, p = 0.41). CONCLUSIONS: Vena contracta imaging by
      TEE color flow mapping is an accurate marker of AR severity. Vena contracta width
      and VC area correlate well with RgF and RgV obtained by intraoperative flow
      probe. Vena contracta width appears to be less afterload-dependent than RgV.

PMID- 11300461
TI  - Are all angiotensin-converting enzyme inhibitors interchangeable?
AB  - In the treatment of most medical conditions, there are many choices. A critical
      question for practicing clinicians is: "Are all drugs within a class
      interchangeable?" In the past decade, the market has seen a proliferation of
      drugs within popular drug classes. The original drugs within a class typically
      have better scientific documentation than the newer ones, which are often
      referred to as "me-too" drugs. Due to a lesser financial investment, the latter
      may be available at a lower cost. Good reasons exist for grouping drugs, however,
      there is no accepted definition of the term "class effect." Although members of a
      drug class share main actions, they may have clinically important differences in
      terms of efficacy and safety. There are many such examples in the literature.
      This article reviews the class effect concept as it applies to the angiotensin
      converting enzyme (ACE) inhibitors. Only half of the 10 ACE inhibitors available
      in the U.S. have been shown to improve survival and reduce morbidity in patients
      with heart failure or myocardial infarction. It is unknown whether the other five
      have the same safety and efficacy profiles or what their optimal doses are. Thus,
      we do not know whether all ACE inhibitors are fully interchangeable. The practice
      of medicine ought to be based on solid scientific evidence, not on assumptions or
      extrapolations. For our patients, such practice is a legitimate expectation.
      Therefore, it seems prudent to recommend that patients requiring ACE inhibitor
      therapy be prescribed one that has been proven effective and safe.

PMID- 11300462
TI  - Modulation of oxidative stress by a selective inhibition of angiotensin II type 1
      receptors in MI rats.
AB  - OBJECTIVES: To examine whether blocking of the renin-angiotensin system (RAS) at
      the angiotensin II type 1 (AT1) receptor site is accompanied by changes in the
      oxidative stress parameters. BACKGROUND: Congestive heart failure in rats after
      myocardial infarction (MI) has been shown to correlate with a decrease in
      antioxidant enzyme activities and an increase in oxidative stress. Inhibition of
      the RAS with captopril improves cardiac function and survival in MI rats with a
      reduction in oxidative stress. METHODS: Myocardial infarction in rats was
      produced by ligation of the left coronary artery. At four weeks after surgery,
      animals from the sham as well as MI groups were treated with losartan (2 mg/ml in
      drinking water daily). At 16 weeks after surgery, the animals were examined for
      hemodynamic function and the hearts were analyzed for antioxidant enzyme
      activities (superoxide dismutase, glutathione peroxidase and catalase) and
      oxidative stress (lipid hydroperoxides, reduced and oxidized glutathione and
      redox ratio). RESULTS: Congestive heart failure was characterized by dyspnea,
      depressed hemodynamic function and presence of lung and liver congestion. This
      was also associated with a decrease in the myocardial catalase (-25%),
      glutathione peroxidase (-38%) and superoxide dismutase (-42%) activities. An
      increase in oxidative stress in these hearts was indicated by an increase in
      lipid hydroperoxides (+67%) and reduction in the redox ratio (-75%). Hemodynamic
      function was better maintained and there were no indications of dyspnea or lung
      or liver congestion in the losartan-treated MI rats. In these animals, myocardial
      oxidative stress was markedly reduced and glutathione peroxidase and catalase
      activities were significantly improved compared with the untreated MI group.
      CONCLUSIONS: Blocking of RAS at the AT1 receptor site without the inhibition of
      angiotensin-converting enzymes modulates heart failure after MI, and this
      beneficial effect is associated with a decrease in oxidative stress. This study
      suggests a newer role for losartan in the treatment of heart failure.

PMID- 11300463
TI  - President's page: convocation address "treat each day as your last and each
      patient as your first: a personal promise to the profession".

PMID- 11300464
TI  - Redefinition of myocardial infarction by a consensus dissenter.

PMID- 11300465
TI  - Benefit of aspirin plus angiotensin-converting enzyme inhibitor.

PMID- 11300466
TI  - Papillary muscle hypothesis of idiopathic left ventricular tachycardia.

PMID- 11300467
TI  - The enigma of primary pulmonary hypertension.

PMID- 11300468
TI  - American College of Cardiology Clinical Expert Consensus Document on Standards
      for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies
      (IVUS). A report of the American College of Cardiology Task Force on Clinical
      Expert Consensus Documents.

PMID- 11300469
TI  - A decade in the life of tumor immunology.

PMID- 11300470
TI  - WT1-specific serum antibodies in patients with leukemia.
AB  - WT1 is an oncogenic protein expressed by the Wilms' tumor gene and overexpressed
      in the majority of acute myelogenous leukemias (AMLs) and chronic myelogenous
      leukemias (CMLs). The current study analyzed the sera of patients with AML and
      CML for the presence of antibodies to full-length and truncated WT1 proteins.
      Sixteen of 63 patients (25%) with AML had serum antibodies reactive with WT1/full
      length protein. Serum antibodies from all 16 were also reactive with WT1/NH2
      terminal protein. By marked contrast, only 2 had reactivity to WT1/COOH-terminal
      protein. Thus, the level of immunological tolerance to the COOH terminus may be
      higher than to the NH2 terminus. The WT1/COOH-terminal protein contains four zinc
      finger domains with homology to other self-proteins. By implication, these
      homologies may be related to the increased immunological tolerance. Results in
      patients with CML were similar with antibodies reactive to WT1/full-length
      protein detectable in serum of 15 of 81 patients (19%). Antibodies reactive with
      WT1/NH2-terminal protein were present in the serum of all 15, whereas antibodies
      reactive with WT1/COOH-terminal protein were present in only 3. By contrast to
      results in leukemia patients, antibodies reactive with WT1/full-length protein
      were detected in only 2 of 96 normal individuals. The greater incidence of
      antibody in leukemia patients provides strong evidence that immunization to the
      WT1 protein occurred as a result of patients bearing malignancy that expresses
      WT1. These data provide further stimulus to test therapeutic vaccines directed
      against WT1 with increased expectation that the vaccines will be able to elicit
      and/or boost an immune response to WT1.

PMID- 11300471
TI  - CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro
      immunogenicity of natural and analogue sequences.
AB  - We have shown previously that HLA-A*0201 melanoma patients can frequently develop
      a CTL response to the cancer testis antigen NY-ESO-1. In the present study, we
      have analyzed in detail the relative antigenicity and in vitro immunogenicity of
      natural and modified NY-ESO-1 peptide sequences. The results of this analysis
      revealed that, although suboptimal for binding to the HLA-A*0201 molecule,
      peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized
      by specific CTL clones derived from three melanoma patients. In contrast,
      peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA
      A*0201, are recognized less efficiently. In agreement with previous data,
      substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino
      acids resulted in a significantly increased binding to HLA-A*0201 molecules as
      well as in an increased CTL recognition, although variable at the clonal level.
      Among natural peptides, NY-ESO-1 157-165 and NY-ESO-1 157-167 exhibited good in
      vitro immunogenicity, whereas peptide NY-ESO-1 155-163 was poorly immunogenic.
      The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201,
      and T-cell receptor was analyzed at the molecular level using a series of variant
      peptides containing single alanine substitutions. The findings reported here have
      significant implications for the formulation of NY-ESO-1-based vaccines as well
      as for the monitoring of either natural or vaccine-induced NY-ESO-1-specific CTL
      responses in cancer patients.

PMID- 11300472
TI  - A new strategy for tumor antigen discovery based on in vitro priming of naive T
      cells with dendritic cells.
AB  - We describe a method for discovery of new tumor antigens that uses dendritic
      cells (DCs) as antigen-presenting cells to prime autologous naive CD4+ and CD8+ T
      cells from healthy donors against tumor proteins and peptides. For the
      identification of HLA class I-restricted tumor antigens, peptides were extracted
      from tumor HLA class I molecules, fractionated by reverse phase-high performance
      liquid chromatography, and loaded onto in vitro-generated DCs to prime naive CD8+
      T cells. Our results show that we were able to prime naive CD8+ T cells in vitro
      to several peptide fractions and generate specificity for the tumor. Electrospray
      ionization mass spectrometry was used to confirm that these fractions contained
      peptides derived from MHC class I molecules, and the primed CD8+ T cells were
      used to further analyze the immunostimulatory peptide fractions. For the
      identification of HLA class II-restricted tumor antigens, we fractionated tumor
      protein extracts using reverse phase-high performance liquid chromatography and
      loaded individual fractions onto DCs to prime naive CD4+ T cells. Our results
      show that we were also able to prime naive CD4+ T cells to several protein
      fractions and generate specificity for the tumor. These results illustrate the
      potential of this method to identify new immunostimulatory MHC class I- and class
      II-restricted tumor antigens.

PMID- 11300473
TI  - Biochemical characterization of the soluble form of tumor antigen MUC1 isolated
      from sera and ascites fluid of breast and pancreatic cancer patients.
AB  - Transmembrane glycoprotein tumor antigen MUC1 that is overexpressed on pancreatic
      and breast tumor cells can be found in large amounts in soluble form in serum and
      ascites fluid. MUC1 has been identified as a target of human antitumor antibody
      and CTL responses that are generated in the absence of helper T cells. The
      soluble form of MUC1 should support generation of helper T cells, but we have
      found recently that this form, although effectively endocytosed by dendritic
      cells, remains trapped in early endosomes and is not trafficked to antigen
      processing compartments. The exact biochemical structure of this form of MUC1 has
      not been elucidated to date, and it is thus not clear what structural
      characteristics may be responsible for its retention in early endosomes. We have
      purified soluble MUC1 from ascites fluid of breast/pancreatic cancer patients
      (ASC-MUC1) and quantitated O-linked carbohydrates. We have altered ASC-MUC1 by
      enzymatic treatment: trypsin or clostripain digestion, desialylation, and further
      in vitro glycosylation. We have found that desialylated ASC-MUC1 was further
      glycosylated by peptidyl N-acetylgalactosamine transferases and was not when
      sialic acid was present. These alterations created new forms of ASC-MUC1 that
      might be handled more efficiently by antigen-presenting cells to generate better
      tumor-specific immunity and used to identify structures that are directly
      involved in retention of this antigen in early endosomes.

PMID- 11300474
TI  - Human T-cell responses to HLA-A-restricted high binding affinity peptides of
      human papillomavirus type 18 proteins E6 and E7.
AB  - Human Papillomaviruses (HPVs) are sexually transmitted pathogens, which are
      implicated in the etiology of cervical cancer. The early proteins E6 and E7 of
      HPV have transforming capacity and interfere with the cell cycle control of
      infected host cells and are essential for the maintenance of the transformed
      state. Identification of MHC class I-restricted, immunogenic peptides derived
      from either the E6 or the E7 protein is essential for the design of vaccines as
      well as the monitoring of clinical trials and immunotherapeutic approaches for
      the treatment of HPV-18-induced carcinomas. We have determined the binding
      affinities for all possible 9-mer peptides spanning the entire E6 and E7 amino
      acid sequence for the HLA-A*0101, HLA-A*0201, HLA-A*0302, HLA-A*1102, and HLA
      A*2402101 molecules by a competition assay with reference peptides, thereby
      establishing the binding peptides as potential cytotoxic T-cell epitopes. From
      the HLA-A*0201 binding peptides, we selected five E6-derived and one E7-derived
      peptide with high affinities for HLA-A*0201. These six peptides were tested for
      their immunogenicity by in vitro immunization assays with purified human CD8+ T
      cells. We identified three HPV-18 E6-derived peptides (ELTEVFEFA, KTVLELTEV, and
      KLPDLCTEL) and the E7-derived peptide TLQDIVLHL to be highly immunogenic.
      Overall, these results will help to design vaccines for the prevention or
      treatment of HPV-18-induced cervical cancer.

PMID- 11300475
TI  - Expansion and functional maturation of human tumor antigen-specific CD8+ T cells
      after vaccination with antigenic peptide.
AB  - Peptide-based vaccines are currently being tested for their ability to induce or
      augment tumor antigen (Ag)-specific CD8+ T-cell responses in cancer patients.
      Here we report that the frequency of circulating CD8+ T cells directed against
      the Melan-A/MART-1 Ag increased >20-fold in an HLA-A2 melanoma patient immunized
      repeatedly with the corresponding antigenic peptide, as assessed by staining with
      HLA-A2/peptide tetramers. Multiparameter flow cytometric analysis demonstrated
      that the increase in total Melan-A-specific cell number was accompanied by a
      marked increase in the proportion of the cells that expressed an activated/memory
      surface phenotype. As assessed by ELISPOT assays and intracellular staining, the
      absolute number of Melan-A-specific cells able to secrete IFN-gamma increased >50
      fold upon vaccination. When tested directly after cell sorting on the basis of
      tetramer staining, Melan-A-specific cells were weakly cytolytic but became highly
      active after in vitro restimulation. Altogether, these results indicate that
      large numbers of functionally active tumor Ag-specific CD8+ T cells can be
      obtained and maintained at high levels after in vivo activation by repeated
      peptide-based vaccination.

PMID- 11300476
TI  - Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T
      lymphocytes correlates with increased intracellular perforin expression and
      enhanced cytotoxicity against HLA-A2-matched cervical tumor cells.
AB  - Human papillomavirus (HPV) infection represents the most important risk factor
      for developing cervical cancer. In this study, we examine the potential of full
      length E7-pulsed autologous dendritic cells (DCs) to induce antigen-specific CTL
      responses from the peripheral blood of healthy individuals against HLA-A2-matched
      HPV-16 and HPV-18-positive tumor target cells in vitro. We show that DCs pulsed
      with E7 oncoprotein can consistently stimulate antigen-specific CTL responses
      that recognize and lyse HPV-16 or HPV-18-positive naturally infected cervical
      cancer cell lines. HPV-negative, EBV-transformed lymphoblastoid cell lines (LCLs)
      sharing the HLA haplotype of the target tumor cells, as well as autologous donor
      LCLs, were not significantly killed by E7-specific CTLs. Cytotoxicity against HLA
      A2-matched HPV-16 and HPV-18 tumor target cells could be significantly inhibited
      by anti-HLA class I and by anti-HLA-A2 monoclonal antibodies. CD8+ CTLs expressed
      variable levels of CD56 and showed a strongly polarized Type 1 cytokine profile.
      Sorting of the CD8+ T cells on the basis of CD56 expression demonstrated that the
      most highly cytotoxic CTLs were CD56+ and expressed higher levels of perforin and
      IFN-gamma, compared with the CD8+/CD56- population. Taken together, these data
      demonstrate that full-length, E7-pulsed DCs can consistently induce E7-specific
      CD8+ CTL responses in healthy individuals that are able to kill naturally HPV-16
      and HPV-18-infected cancer cells, and that CD56 expression defines a subset of
      CD8+ CTLs with high cytolytic activity against tumor cells.

PMID- 11300477
TI  - Lack of ignorance to tumor antigens: evaluation using nominal antigen
      transfection and T-cell receptor transgenic lymphocytes in Lyons-Parish analysis-
      implications for tumor tolerance.
AB  - A substantial body of literature has described weak antitumor CTL responses in
      tumor-bearing hosts, and a number of authors have suggested that tumor tissue in
      some way sequesters antigen from the immune system, a failure of the tumor
      specific immune response largely attributable to "ignorance." To evaluate this in
      a tumor model, we stably transfected murine tumor cell lines with genes coding
      for the nominal antigens influenza hemagglutinin (HA) or ovalbumin (OVA) and
      adoptively transferred HA- or OVA-specific T-cell receptor-transgenic, CD8
      positive T cells into mice-bearing these tumors. Tumor antigen cross-presentation
      within draining lymph nodes (LNs) was then examined using Lyons-Parish analysis,
      detection of a proliferative response of 5,6-carboxyfluorescein diacetate
      succinimidyl ester-labeled CD8 T cells from T-cell receptor mice using flow
      cytometric analysis. Our studies demonstrate clearly that tumor antigens are
      constitutively presented in LNs draining tumors and can stimulate a T-cell
      proliferative response. This lack of ignorance was not simply attributable to the
      model chosen, because it was seen with three different cell lines, two different
      antigens, and two different mouse strains. Furthermore, it occurred regardless of
      whether these tumor antigens were expressed as cytoplasmic, transmembrane, or
      secreted proteins. When tumor antigens were present in low concentrations,
      antigen cross-presentation was not absent but simply delayed. Interestingly,
      tumor antigen cross-presentation remained localized to the LNs draining the tumor
      throughout the period of tumor growth. Curiously, in animals where tumors failed
      to grow, evidence of continued cross-presentation of the tumor antigen was seen
      up to 6 months after tumor inoculation. These data suggest that ignorance is not
      an explanation for the failure of the host immune system to respond to tumor
      antigens.

PMID- 11300478
TI  - Surrogate markers of antitumor responses: in vitro activation of T cells by
      autologous tumor peptides.
AB  - The increasing ability to augment antitumor immunity in model systems has led to
      increased numbers of clinical trials. However, progress in detecting immune
      responses by patients against autologous tumors has been slow. Although a
      considerable number of tumor antigens, as well as peptides derived from them, and
      the MHC determinants together with which they are presented have been identified
      for melanoma, this is not so for the majority of solid tumors. Furthermore, tumor
      cells themselves are poor stimulators of immunity. Thus, approaches that do not
      depend upon defined antigens or using tumor cells as stimulators would be
      desirable. To attempt to measure immune responses in these situations, we tested
      whether total peptides, prepared from autologous tumor tissue, stimulated
      cytokine release by T cells. Peripheral blood mononuclear cells (PBMCs) were
      mixed with antigen-presenting cells (APCs), pulsed with tumor peptides, and
      tested in the ELISPOT assay for IFN-gamma secretion. Few spots were obtained when
      PBMCs were cultured with unpulsed APCs or in wells with peptide-pulsed APC alone.
      In contrast, a strong response was seen when PBMCs were cultured with APCs that
      had been pulsed with autologous total tumor peptides. This system should help to
      identify those immunotherapeutic approaches that induce responses against tumor
      cells in vivo. Because different cytokine profiles are associated with distinct
      arms of the immune response, testing in the ELISPOT assay may also help us
      understand the mechanisms responsible.

PMID- 11300479
TI  - Genetic approach to insight into the immunobiology of human dendritic cells and
      identification of CD84-H1, a novel CD84 homologue.
AB  - To better understand the immunobiology of dendritic cells (DCs), we took the
      expressed sequence tag (EST) approach to describe their transcript profile and
      discovered novel genes. ESTs (n = 25,668) were generated from monocyte-derived
      DCs, and 15,863 ESTs (61.8%) represented unique genes in GenBank. Integration of
      ESTs allowed for the generation of a profile of 4,367 known genes and
      identification of > 100 novel genes. HLA-DR invariant chain p33, cathepsin D, HLA
      DR alpha chain, beta2-microglobulin, HLA-DP beta chain, CD11a, and mannose
      receptor were in the top 30 transcripts, and 451 known genes were potentially
      associated with the immunobiology of DCs. This transcript profile was consistent
      with the unique antigen-presenting capacity of DCs and provided invaluable
      information to better understand the immunobiology of DCs. On the basis of the
      EST database, a full-length novel gene was identified that exhibited close
      homology with CD84; it was designated CD84-H1. The full-length cDNA of CD84-H1
      contained an open reading frame of 870 bp encoding a type I transmembrane protein
      of 289 amino acids. Consistent with the structural feature of the CD2 family, the
      predicted 270-amino acid mature protein of CD84-H1 contained two extracellular
      immunoglobulin-like domains that shared homology with CD2 family members, e.g.,
      CD84, Ly-9, CD48, and signaling lymphocyte activation molecule. Its intracellular
      domain was short and contained no putative signaling structure. Northern blot
      analysis revealed that CD84-H1 expression was predominantly restricted in
      hematopoietic tissues. Reverse transcription-PCR analysis showed that it was
      widely expressed in the immune cells, including monocytes, DCs, B cells, and T
      cells. These data indicate that CD84-H1 may be relevant to immune responses.

PMID- 11300480
TI  - Inhibition of mammary carcinogenesis by systemic interleukin 12 or p185neu DNA
      vaccination in Her-2/neu transgenic BALB/c mice.
AB  - Because BALB/c mice transgenic for the rat Her-2/neu oncogene develop multifocal
      carcinomas in all mammary glands by week 33, they constitute an aggressive model
      for investigation of treatments designed to oppose mammary carcinogenesis.
      Nonspecific immune reaction elicited by systemic interleukin (IL)-12 both delayed
      the appearance of the first tumor and reduced the number of glands affected.
      However, only 5% of mice were tumor free at week 33. On the other hand, specific
      vaccination with plasmids encoding for the rat p185neu resulted in a further
      delay, so much so that 58% of mice were tumor free at week 33. No CTL response
      was evoked in either IL-12-treated or DNA-vaccinated mice, whereas an anti-rat
      p185neu antibody response was evident in the latter. Pathological examinations
      showed that in both IL-12-treated and DNA-vaccinated mice, the tumor growth area
      was infiltrated by reactive cells associated with expression of endothelial
      adhesion molecules and antiangiogenic proinflammatory cytokines. In the
      vaccinated mice, reduction of the number of cells expressing rat p185neu was
      combined with down-regulation of its membrane expression and even a marked
      inhibition in development of the terminal ductal lobular units. The reactive
      infiltrate in vaccinated mice contained numerous granulocytes that likely played
      an antiangiogenic and angiodestructive role and also joined other cells in the
      antibody-mediated killing of the r-p185neu+ cells. These results suggest that the
      elicitation of nonspecific and specific immunity could be beneficially used in
      individuals with a high risk of developing tumors.

PMID- 11300481
TI  - Recombinant human papillomavirus type 16 E7 protein as a model antigen to study
      the vaccine potential in control and E7 transgenic mice.
AB  - The early genes E6 and E7 of human papillomavirus type 16 (HPV16) are
      consistently and exclusively expressed in HPV16-induced cancer lesions and play
      major roles in the development and maintenance of the malignant phenotype.
      Because this protein is a good example of a tumor-associated antigen, we have
      used E7 as a model antigen to test the potential of an experimental vaccine as an
      immunotherapeutic approach. In this study, we used a murine E7-expressing tumor
      model (TC1 cells) to assess effects of an E7-based vaccine on tumor growth. We
      show that vaccination with the E7 protein, formulated in the SmithKline Beecham
      Biologicals proprietary adjuvants (SBAS 1 and SBAS 2), leads to the rejection of
      pre-established tumors. Tumor rejection was associated with the induction of a
      strong systemic T helper 1 response, including CTLs, and the presence of an
      inflammatory infiltrate within the regressing tumor. Because most identified
      tumor-associated antigens are self antigens rather viral antigens, we used E7
      transgenic mice to evaluate the E7-based vaccine in conditions where E7 is a self
      antigen. Transgenic mice, which constitutively and specifically express the E7
      HPV16 gene in the thyroid epithelium, rapidly develop thyroid goiters and, after
      several months, thyroid carcinomas. We show that E7-specific antibodies and CD4 T
      helper responses can be obtained by vaccinating E7 transgenic mice, although a
      CTL response was not detected. Despite the absence of measurable CTL responses,
      vaccination still reduced the growth of pre-established TC1 tumors, although less
      efficiently than in nontransgenic animals, but was unable to suppress or delay
      the development of the spontaneous thyroid pathology.

PMID- 11300482
TI  - MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively
      transferred in vivo.
AB  - We have reported previously that MUC1 transgenic mice with spontaneous tumors of
      the pancreas (designated MET) naturally develop MHC class I-restricted, MUC1
      specific CTLs as tumors progress (P. Mukherjee et al., J. Immunol., 165: 3451
      3460, 2000). From these MET mice, we have isolated, expanded, and cloned
      naturally occurring MUC1-specific CTLs in vitro. In this report, we show that the
      CTL line is predominantly CD8+ T cells and expresses T-cell receptor Vbeta chains
      5.1/5.2, 11, 13, and 2 and Valpha chains 2, 8.3, 3.2, and 11.1/11.2. These CTLs
      recognize several epitopes on the MUC1 tandem repeat with highest affinity to
      APGSTAPPA. The CTL clone, on the other hand, is 100% CD8+ cells and expresses a
      single Vbeta chain of 5.1/5.2 and Valpha2. It recognizes only the H-2Db class I
      restricted epitope of MUC1, APGSTAPPA. When adoptively transferred, the CTLs were
      effective in eradicating MUC1-expressing injected tumor cells including mammary
      gland cells (C57mg) and B16 melanomas. These results suggest that MUC1-specific
      CTLs are capable of possibly preventing, or at least substantially delaying, MUC1
      expressing tumor formation. To our knowledge, this is the first evidence that
      demonstrates that the naturally occurring MUC1-specific CTLs isolated from one
      tumor model has antitumor effects on other MUC1-expressing tumors in vivo.
      Therefore, our data confirm that MUC1 is an important tumor rejection antigen and
      can serve as a target for immunotherapy.

PMID- 11300483
TI  - Protective immunity against human carcinoembryonic antigen (CEA) induced by an
      oral DNA vaccine in CEA-transgenic mice.
AB  - Peripheral T-cell tolerance toward human carcinoembryonic self-antigen (CEA) was
      broken in CEA-transgenic C57BL/6J mice by an oral CEA-based DNA vaccine. This
      vaccine, delivered by the live, attenuated AroA- strain of Salmonella typhimurium
      (SL7207), induced tumor-protective immunity mediated by MHC class I-restricted
      CD8+ T cells. Activation of these T cells was indicated by increased secretion of
      proinflammatory cytokines IFN-gamma, interleukin (IL)-12 and
      granulocyte/macrophage-colony stimulating factor, as well as specific tumor
      rejection and growth suppression in vaccinated CEA-transgenic mice after a lethal
      challenge with murine MC38 colon carcinoma cells. These tumor cells were double
      transfected with CEA and the human epithelial cell adhesion molecule (Ep-CAM)/KSA
      and consequently served as a docking site for a recombinant antibody-IL2 fusion
      protein (KS1/4-IL2) recognizing KSA. Importantly, the efficacy of the tumor
      protective immune response was markedly increased by boosts with this antibody
      IL2 fusion protein, resulting in more effective tumor rejection coupled with
      increased expression of costimulatory molecules B7.2/B7.2 and intercellular
      adhesion molecule 1 (ICAM-1) on dendritic cells and intensified release of
      proinflammatory cytokines IFN-gamma, IL-12, and granulocyte/macrophage-colony
      stimulating factor from T cells of successfully vaccinated CEA-transgenic
      C57BL/6J mice. Increased T-cell activation mediated by boosts with KS1/4-IL2
      fusion protein after tumor cell challenge was further indicated by expanded
      expression of T-cell activation markers CD25, CD28, CD69, and LFA-1. The
      application of such CEA-based DNA vaccines and its further improved versions may
      ultimately prove useful in combination therapies directed against human
      carcinomas expressing CEA self-antigens.

PMID- 11300484
TI  - Dendritic cells, loaded with recombinant bacteria expressing tumor antigens,
      induce a protective tumor-specific response.
AB  - Dendritic cells (DCs) are considered the most potent antigen-presenting cells and
      probably the only ones able to prime naive T cells. Indeed, DCs are distributed
      in tissues that interface the external environment, where they act as sentinels
      for incoming bacteria, viruses, and fungi. We have previously analyzed the
      capacity of DCs to interact with bacteria, and we have shown that bacteria can
      act as "Trojan horses," delivering heterologous proteins to DCs in a processed
      form that allows extremely efficient loading of both MHC class I and class II
      molecules. In this study, we have optimized the usage of recombinant bacteria as
      an antigen delivery system for DCs, with the aim to develop a new DC vaccination
      strategy in antitumor immunity. We have focused on a low immunogenic antigen, the
      tyrosinase-related protein-2 (Trp-2), a self-antigen expressed in mouse and human
      melanoma for which induction of antitumor immunity has proven to be very
      ineffective. We have given mice injections of either Trp-2/recombinant bacteria
      loaded DCs or with bacteria alone engineered to express the Trp-2 melanoma
      antigen. We have shown that only DCs loaded with recombinant bacteria, but not
      with wild-type bacteria, were able to induce Trp-2-specific CTLs and immunity
      against the B16 tumor. Immunity was obtained in experiments of tumor vaccination
      as well as in experiments of tumor therapy. When therapy with bacteria-loaded DCs
      was performed in B16 tumor-bearing mice, 60% of the treated mice were tumor free
      2 months after the initial tumor growth.

PMID- 11300485
TI  - Tracking the common ancestry of antigenically distinct cancer variants.
AB  - In the months and years after first diagnosis, cancers often show an increase in
      their malignancy such as faster growth, resistance to chemo- and/or hormonal
      therapy, and loss of antigens targeted by immunotherapy. Our objective was to
      develop a model in which one can track the changes occurring as a result of in
      vivo immune selection, such as the loss of antigen, the emergence of previously
      hidden antigens, or the acquisition of new tumor-specific antigens. In this
      study, we used the primary UV-induced murine tumor 8101, which consists
      predominantly of regressor tumor cells that express the immunodominant mutant p68
      antigen, but this tumor also contains progressor variants that have lost this
      antigen. To search for tumor-specific antigens on the immune escape progressors,
      we raised CD8+ T cells specific for these variants. We found that one of the
      escape variants expressed a previously unrecognized, unique tumor-specific
      antigen. However, this unique antigen was not readily detectable on any of the
      other 8101 lines we tested. To prove that these antigenically distinct cancer
      variants had indeed been derived from the same tumor and neither represented new
      tumors nor contaminations by other cell lines, we used unique tumor-specific p53
      mutations as a lineage-specific marker to demonstrate that these antigenically
      distinct progressor variants were derived from the 8101 tumor. Because p53
      mutations occur very early during UV carcinogenesis and vary from tumor to tumor,
      they provide convenient reliable markers for tracking the origin of cancers
      arising after immune selection or immunotherapy.

PMID- 11300486
TI  - A murine model for the effects of pelvic radiation and cisplatin chemotherapy on
      human papillomavirus vaccine efficacy.
AB  - Therapeutic human papillomavirus (HPV) vaccines for cervical cancer depend on a
      competent immune system to be effective. However, cancer patients are often found
      to be immunosuppressed, which could be attributable to prior radiation,
      chemotherapy, or the tumor burden itself. This study investigated whether pelvic
      radiation or cisplatin treatment affected the efficacy of an HPV vaccine and how
      long these effects lasted. Mice were given pelvic radiation, 2 Gy/day to a total
      dose of 45 Gy, or 5 mg/kg/week of cisplatin for 3 weeks. Mice were then immunized
      with an HPV-16 peptide vaccine between 0 and 16 weeks after their treatment. An
      ELISPOT analysis revealed that a reduced level of peptide-specific, IFNgamma
      producing spleen cells was present in immunized mice treated previously with
      pelvic radiation or cisplatin compared with immunized mice that had not been
      treated. However, when mice were challenged with HPV-16-expressing tumor cells,
      immunized mice developed no tumors, regardless of prior treatment, whereas
      nonimmunized mice did develop tumors. Our results suggest that pretreatment with
      pelvic radiation or cisplatin alone does not prevent the induction of an
      effective immune response by a peptide vaccine. These data will have important
      implications for immunotherapeutic treatment of pretreated cancer patients,
      especially in the adjuvant setting when immunosuppression by tumor burden would
      be low.

PMID- 11300487
TI  - Engineering enhancement of immune responses to DNA-based vaccines in a prostate
      cancer model in rhesus macaques through the use of cytokine gene adjuvants.
AB  - DNA immunization is an important vaccination technique that is being explored as
      an immunotherapeutic strategy against a variety of infectious diseases as well as
      cancer. We have been investigating the utility of DNA-based vaccine strategy
      against prostate cancer. We have developed a DNA vaccine construct that encodes
      for the human prostate specific antigen (PSA) gene. PSA expression is limited to
      prostate cells, and the level of PSA expression is substantially increased in
      prostate cancer cells. This tissue specificity makes PSA a potential target for
      the development of immunotherapies against prostate cancer. A DNA-based PSA
      vaccine was used to elicit PSA-specific host immune responses in rodent and
      nonhuman primate models. In an effort to enhance the clinical utility of the DNA
      based PSA vaccine, we also examined the use of cytokine gene adjuvants to
      modulate vaccine-induced immune responses in these animal models. We observed
      that pCPSA vaccine-induced humoral and cellular immune responses can be modulated
      through the coimmunization with cytokine genes in mice, and these enhancement
      effects on the PSA-specific cellular responses were extended in macaques. More
      specifically, coimmunization with interleukin (IL)-2 cDNA construct resulted in a
      significant enhancement of PSA-specific antibody responses in both mice and
      macaque models. In contrast, coinjection of IL-12 resulted in reduction of
      antibody responses in both models. In mice, the groups coimmunized with IL-2, IL
      12, or IL-18 showed a dramatic increase in T helper cell proliferation over the
      results with pCPSA alone. These results support that further evaluation of this
      vaccination strategy to treat prostate cancer is warranted.

PMID- 11300488
TI  - Visualization of immunotoxin-mediated tumor cell death in vivo.
AB  - We present a novel methodology to visualize tumor cells directly in a whole
      mouse. This technique combines immunohistochemistry with whole mouse sectioning.
      It lets one see the exact distribution of tumor cells throughout an animal and
      how effectively these cells are eliminated by cancer therapeutics. We used this
      technique to assess the efficacy of a T cell-specific immunotoxin in a severe
      combined immunodeficient mouse model of human T-cell leukemia. Severe combined
      immunodeficient mice were injected with one of two human T-cell acute
      lymphoblastic leukemia cell lines (Molt 3 and Molt 13) and were either left
      untreated or were treated with DA7, an immunotoxin specific for the T cell
      associated antigen CD7. Mice were sacrificed after tumor cell injection and
      immunotoxin therapy, whole mouse cross-sections were prepared, and tumor cells in
      the sections were visualized by immunohistochemistry. No tumor cells were
      detected in DA7-treated mice injected with Molt 3, consistent with the long-term
      survival of this group and the sensitivity of Molt 3 to DA7 in vitro. In
      contrast, DA7 treatment did not visibly eliminate tumor cells in mice challenged
      with Molt 13, nor did it result in their long-term survival. Furthermore, tumor
      cells were detected in areas that may have otherwise been overlooked, and their
      distribution differed from that of mice injected with Molt 13 alone. These
      analyses indicate that whole mouse sectioning will be a valuable tool for
      assessing residual disease in the preclinical evaluation of cancer therapeutics.

PMID- 11300489
TI  - Immunization of HLA-A2+ melanoma patients with MAGE-3 or MelanA peptide-pulsed
      autologous peripheral blood mononuclear cells plus recombinant human interleukin
      12.
AB  - Vaccination with dendritic cells (DCs) pulsed with tumor antigen peptides has
      shown promise in the treatment of melanoma. Interleukin (IL)-12 production by DCs
      is a key component for their efficacy. Murine studies have shown that IL-12
      promotes potent antitumor immunization when coadministered with peptides loaded
      onto other class I MHC+ cells, thus bypassing the need to use DCs. The easiest
      cell source to obtain in large quantity from human patients is peripheral blood
      mononuclear cells (PBMCs). A Phase I clinical trial was thus performed in
      patients with metastatic melanoma using immunization with autologous PBMCs pulsed
      with a MAGE-3 or a MelanA peptide, coadministered with various doses of
      recombinant human (rh)IL-12. Patients receiving low-to-moderate doses of rhIL-12
      developed increased specific CD8+ T-cell responses. Of the eight patients showing
      increased immunity, six had evidence of clinical activity, with one complete, one
      partial, one minor, and three mixed responses observed. In two patients with
      mixed responses, growing tumors were found to lack expression of the antigen used
      to immunize. Thus, vaccination with peptide-pulsed PBMCs plus rhIL-12 induces
      specific immunity and has clinical activity, without the need to generate DCs.
      Outgrowth of antigen-negative tumors argues for the future development of
      polyepitope vaccines.

PMID- 11300490
TI  - Detection of CD4 T-cell responses to a tumor vaccine by cytokine flow cytometry.
AB  - Cytokine flow cytometry (CFC) is a simple and powerful method for measuring
      antigen-specific T-cell responses by detection of intracellular cytokine
      staining. We applied this method to the detection of CD4 T-cell responses to
      tumor vaccines. Patients with multiple myeloma were immunized against their
      autologous tumor immunoglobulin idiotype, using antigen-pulsed dendritic cell
      vaccination. Blood samples were drawn before and after vaccination, and CFC and
      proliferation assays were performed. For CFC, whole blood was incubated overnight
      with antigen in the presence of costimulatory antibodies to CD28 and CD49d. The
      blood was then treated with EDTA, erythrocytes were lysed, and leukocytes were
      fixed, permeabilized, and stained for intracellular cytokines [tumor necrosis
      factor-alpha (TNF-alpha) or IFN-gamma], CD4, and CD69. Cells were analyzed by
      flow cytometry and cytokine-producing CD69+ cells enumerated as a percentage of
      CD4 cells. Of nine patients analyzed, three demonstrated detectable CFC responses
      to tumor immunoglobulin and/or keyhole limpet hemocyanin (KLH) after vaccination.
      One of these patients responded only to KLH, whereas the other two responded to
      both tumor immunoglobulin and KLH. Most responses were detected with both TNF
      alpha and IFN-gamma, but one patient's KLH response was detected only with TNF
      alpha. There was a positive, but not strong, correlation of cytokine responses
      with proliferative responses to KLH. Although further follow-up and correlation
      with clinical outcome is needed, CFC may represent a simple yet detailed
      assessment of T-cell frequencies and subsets responding to cancer vaccines.

PMID- 11300491
TI  - Analysis of a natural immune response against tumor antigens in a melanoma
      survivor: lessons applicable to clinical trial evaluations.
AB  - The long-term survival of some patients with metastatic melanoma may be
      attributable in part to cellular immune responses to melanoma antigens. However,
      little is known about the level of CTL reactivity in vivo that is required for
      immunological control of tumor progression. In the present report, T-cell
      responses were evaluated with lymphocytes obtained from tumor-involved nodes and
      peripheral blood of a long-term melanoma survivor. Using an ELISPOT assay,
      naturally occurring functional T cells, which recognize the peptide ALLAVGATK
      (gp100(17-25)) plus two other HLA-A3 restricted peptides, were detected in a
      tumor-involved lymph node. The ALLAVGATK-reactive T cells were also evaluated by
      MHC-tetramers staining and were found to be CD8+ CD45RO+ L-selectin(-) CD11a+,
      suggesting that they are antigen experienced and have a memory phenotype.
      Unstimulated peripheral blood lymphocytes from the same patient demonstrated no
      detectable T-cell responses; however, a single stimulation with ALLAVGATK peptide
      in vitro resulted in a dramatic expansion of peptide-reactive CTLs. This patient,
      with evidence of tumor-reactive CTLs targeted to several tumor antigens in a
      tumor-involved lymph node and with evidence of a circulating memory T-cell
      response, has remained disease-free for 6 years, despite prior bulky nodal
      metastasis. In contrast, three HLA-A3+ patients with rapidly progressive
      metastatic melanoma had no detectable T-cell response in tumor-involved nodes or
      peripheral blood lymphocytes, even after peptide stimulation ex vivo. The
      presented data are consistent with a systemic polyvalent immune response against
      tumor in this long-term survivor. These data provide an estimate of the level of
      CTL response that may be associated with protection from tumor recurrence.

PMID- 11300492
TI  - Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal
      melanoma.
AB  - A 49-year-old patient with primary, recurrent melanoma on the lower extremity
      developed metastatic leptomeningeal melanoma that did not respond to treatment
      with radiation therapy or intrathecal interleukin 2 (IL-2). Disease was
      characterized by neurological symptoms, including loss of hearing, loss of short
      term memory, and gait disturbance. CD8+ CTLs were generated in vitro using
      autologous dendritic cells pulsed with peptides from the melanoma-associated
      antigens tyrosinase (145-156), Melan-A/MART-1 (26-35), and gp100/Pmel 17 (209
      217). The CTLs exhibited up to 74% specific lysis against peptide-pulsed
      autologous EBV-transformed B cells, with Melan-A-specific CTLs yielding the
      greatest lytic activity. CD8+ CTLs possessed a type 1 cytokine profile,
      expressing tumor necrosis factor alpha and IFNgamma but not IL-4. Infusions of
      CTLs were supported with systemic low-dose IL-2 administration. 111In labeling
      and computerized gamma imaging were used to monitor the distribution of CTLs up
      to 48 h after infusion. Intra-arterial delivery via the right carotid artery was
      followed by redistribution of the CTLs to the lungs, liver, and spleen within 16
      h. In contrast, delivery via an indwelling Ommaya reservoir resulted in prolonged
      retention of CTLs within the brain for at least 48 h after infusion. Marked but
      transient elevations in tumor necrosis factor alpha, IFN-gamma, and IL-6 in the
      cerebrospinal fluid were observed within 4 h of CTL infusion. There was no
      evidence of tumor progression throughout the treatment period, and clinically the
      patient showed some resolution of neurological symptoms.

PMID- 11300493
TI  - Systemic and local immunosuppression in pancreatic cancer patients.
AB  - Pancreatic cancer is characterized by an extremely poor prognosis. For the
      development of more effective immunotherapies, the systemic and local
      immunological escape mechanisms need to be further elaborated. These mechanisms
      may include the secretion of immunosuppressive cytokines, the local hindrance of
      tumor-infiltrating lymphocytes (TILs), or the loss of the signal transducing CD3
      zeta-chain of TILs. In this study, we have analyzed these parameters in 116
      patients suffering from pancreatic ductal adenocarcinoma. Mean concentrations of
      interleukin (IL)-10 and transforming growth factor-beta1/2 were considerably
      higher than in control sera (P < 0.0001). Disseminated tumor cells were found in
      16 of 39 cases. In 28 of 33 surgical specimens, TILs did not reach tumor cells in
      significant numbers, being "trapped" in the peritumoral tissues. We suggest this
      as a simple but highly effective tumor escape mechanism. In cases of a TIL/tumor
      cell contact, CD3 zeta was mostly lost. Overall, 27 of 33 surgical specimens, 9
      of 19 peritumoral lymph nodes, and 13 of 25 peritoneal lavage specimens showed
      significant loss of CD3 zeta (P < 0.02). Elevated concentrations of IL-10/TGF
      beta1/2 were, in all but one of three cases, correlated with a CD3 zeta loss in
      corresponding specimens. Patients with disseminated tumor cells also showed a CD3
      zeta loss in all but two corresponding tumor specimens. These results present
      strong evidence for an active systemic immunosuppression in pancreatic cancer, as
      shown by elevated IL-10 and TGF-beta1/2 serum levels as well as the presence of
      disseminated tumor cells. Killing of tumor cells by potentially cytotoxic TILs is
      obviously suppressed by the prevention of a direct TIL/tumor cell contact and the
      inactivation of TILs, as shown by a severe loss of CD3 zeta. In addition to
      active immunization strategies, successful immunotherapies have to focus on
      restoring in vivo T-cell function to improve the almost always fatal prognosis of
      pancreatic cancer.

PMID- 11300494
TI  - Suppressed T-cell receptor zeta chain expression and cytokine production in
      pancreatic cancer patients.
AB  - Suppression of various functions of T cells derived from cancer patients has been
      linked previously to changes in the T-cell receptor (TCR)-associated signal
      transduction molecules, in particular the zeta chain of the TCR complex. In this
      study, we have examined the TCRzeta chain expression and cytokine production in
      vivo and in vitro in T cells of patients with metastatic adenocarcinomas of the
      pancreas that participated in a Phase I clinical trial of the MUC1 peptide plus
      bacillus Calmette-Guerin cancer vaccine. A majority of the patients had reduced
      TCRzeta chain expression and interleukin 4 production by T cells, and all of the
      patients showed decreased production of IFN-gamma of their peripheral T cells
      when compared with healthy individuals. Peripheral blood T cells were activated
      with the phorbol ester phorbol myrisate acetate and ionomycin to show that
      although aberrant TCRzeta chain expression and decreased cytokine production were
      often correlated, the reduced cytokine production was not simply a consequence of
      an impaired TCRzeta chain expression. Rather, these are two separate but parallel
      defects in signal transduction in T cells, which are potentially modulated by the
      same mechanisms. Half of the patients showed an improvement for TCRzeta chain or
      IFN-gamma expression after vaccination.

PMID- 11300495
TI  - Tumor-induced sensitivity to apoptosis in T cells from patients with renal cell
      carcinoma: role of nuclear factor-kappaB suppression.
AB  - Antitumor immunity fails to adequately develop in many cancer patients, including
      those with renal cell carcinoma (RCC). A number of different mechanisms have been
      proposed to explain the immune dysfunction observed in cancer patient T cells.
      Here we show that T cells from RCC patients display increased sensitivity to
      apoptosis. Tumor-infiltrating lymphocytes (TILs) display the most profound
      sensitivity, because 10-15% of those cells are apoptotic when assessed by
      terminal deoxynucleotidyltransferase-mediated nick end labeling in situ, and the
      number of apoptotic TILs further increases after 24 h of culture. Peripheral
      blood T cells from RCC patients are not directly apoptotic, although T
      lymphocytes derived from 40% of those individuals undergo activation-induced cell
      death (AICD) upon in vitro stimulation with phorbol myristate acetate and
      ionomycin. This is in contrast to T cells from normal individuals, which are
      resistant to AICD. TILs and peripheral blood T cells from RCC patients also
      exhibit impaired activation of the transcription factor, nuclear factor (NF)
      kappaB. Additional findings presented here indicate that the heightened
      sensitivity of patient T cells to apoptosis may be tumor induced, because
      supernatants from RCC explants sensitize, and in some instances directly induce,
      normal T cells to apoptosis. These same supernatants also inhibit NF-kappaB
      activation. RCC-derived gangliosides may represent one soluble tumor product
      capable of sensitizing T cells to apoptosis. Pretreatment with neuraminidase, but
      not proteinase K, abrogated the suppressive effects of tumor supernatants on both
      NF-kappaB activation and apoptosis. Additionally, gangliosides isolated from
      tumor supernatants not only inhibited NF-kappaB activation but also sensitized T
      cells to AICD. These findings demonstrate that tumor-derived soluble products,
      including gangliosides, may contribute to the immune dysfunction of T cells by
      altering their sensitivity to apoptosis.

PMID- 11300496
TI  - Decreased zeta chain expression and apoptosis in CD3+ peripheral blood T
      lymphocytes of patients with melanoma.
AB  - Expression of T-cell receptor- or Fcgamma receptor III-associated signal
      transducing zeta chain is important for the functional integrity of immune cells.
      We found that significantly higher proportions of circulating CD3+ T cells as
      well as natural killer cells had low or absent expression of the zeta chain in
      patients with advanced melanoma than in normal donors (P < 0.0005). Decreased
      zeta expression was always observed in a small subset of circulating CD3+ T cells
      that were in the process of apoptosis, i.e., bound Annexin V or were terminal
      deoxynucleotidyl transferase-mediated nick end labeling positive. Up to 80% of T
      cells in the peripheral blood of patients with melanoma were Fas+, with the mean
      percentage of Fas+CD3+ cells significantly higher in patients (P < 0.004) than
      normal controls. These Fas+CD3+ T cells were found to preferentially undergo
      apoptosis. Annexin V binding, the loss of Fas expression from the cell surface as
      well as zeta down-regulation, which are associated with early apoptosis, were
      detected in a proportion of circulating Fas+CD3+. In Jurkat cells incubated with
      agonistic anti-Fas antibody (CH-11), a rapid loss of Fas expression from the cell
      surface coincided with Annexin V binding and preceded the loss of zeta chain
      during early apoptosis. In a subset of Jurkat cells coincubated with human
      melanoma cells, Annexin V binding and zeta degradation as well as DNA
      fragmentation were observed, indicating that the tumor induced T-cell death.
      Triggering of death receptors expressed on activated T lymphocytes was
      accompanied by the loss of zeta expression. On the other hand, soluble factors
      secreted by melanoma cells induced down-regulation but no apoptosis in activated
      normal T cells. In the circulation of patients with melanoma, apoptosis of immune
      effector cells may be related to the state of chronic activation, resulting in
      the up-regulation of death receptors and increased susceptibility to apoptosis.

PMID- 11300497
TI  - L-Arginine regulates the expression of the T-cell receptor zeta chain (CD3zeta)
      in Jurkat cells.
AB  - L-Arginine is a versatile amino acid that plays a central role in the normal
      function of several organ systems including the immune system. Its availability
      is tightly controlled and varies significantly in different organs and tissues in
      the body. L-Arginine plays an important role in supporting T-cell proliferation.
      Its depletion in certain disease states results in a diminished T-cell response.
      The main purpose of this study was to determine the effect of the depletion of L
      arginine on the expression of the T-cell receptor (TCR) proteins. When the helper
      T-cell line Jurkat was cultured in arginine-free medium, there was a preferential
      decrease in the expression of the TCR zeta chain (CD3zeta). The reduced
      expression of CD3zeta was observed within 24 h of culture in L-arginine-free
      medium and was completely reversed with the replenishment of L-arginine.
      Furthermore, the absence of L-arginine blocked the normal re-expression of the
      TCR that had been internalized after antigen stimulation. There also was a
      significant decrease in proliferation of Jurkat cells in the absence of L
      arginine; however, L-arginine depletion did not prevent the up-regulation of the
      interleukin 2 receptor chains upon stimulation, nor did it significantly diminish
      the production of interleukin 2. The changes in the expression of CD3zeta chain
      were not induced by apoptosis. Thus, the availability of L-arginine in the
      microenvironment may play a significant role in regulating the expression of the
      TCR.

PMID- 11300498
TI  - Relative resistance of fresh isolates of melanoma to tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
AB  - In previous studies, we have shown that tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) could induce varying degrees of apoptosis in
      approximately two-thirds of human melanoma lines. In the present study, we have
      examined the sensitivity of fresh isolates and early passages of melanoma cells
      to TRAIL-induced apoptosis from eight patients. We found that fresh isolates were
      relatively resistant to TRAIL-induced apoptosis and that this appeared to be
      associated with low TRAIL death receptor (TRAIL-R) expression. TRAIL-R expression
      was also undetectable in tissue sections from the same melanoma. We attempted to
      create a model for these findings by generation of TRAIL-resistant melanoma lines
      from TRAIL-sensitive lines grown for prolonged periods in TRAIL. The resulting
      TRAIL-resistant melanoma cell lines had low TRAIL-R expression, and sensitivity
      to TRAIL was increased rapidly by pretreatment with proteasome inhibitors known
      to inhibit activation of nuclear factor-kappaB. However, the latter treatment had
      no significant effect on the sensitivity of fresh isolates to TRAIL. The levels
      of the inhibitors of apoptosis, Flice-like inhibitory protein and Bcl-2, also did
      not relate to resistance to TRAIL-induced apoptosis. These results suggest that
      down-regulation of TRAIL-R on melanoma cells may be the primary determinant of
      resistance of fresh isolates to TRAIL, and the basis for this requires further
      investigation.

PMID- 11300499
TI  - Tumor necrosis factor-alpha-promoted expression of Bcl-2 and inhibition of
      mitochondrial cytochrome c release mediate resistance of mature dendritic cells
      to melanoma-induced apoptosis.
AB  - Melanoma escapes host defenses through a variety of means, including the
      elimination of immune effector cells within the tumor microenvironment. We have
      reported recently that murine and human tumors including melanoma induce
      premature apoptosis of dendritic cells both in vitro and in vivo. In this study,
      we have demonstrated that overexpression of the Bcl-2 protein family member Bcl
      xL rescued murine dendritic cells (DCs) from melanoma-induced death in vitro.
      Another successful protection approach was tumor necrosis factor (TNF)-alpha
      promoted sustained expression of the antiapoptotic protein Bcl-2 within dendritic
      cells. This effect of TNF-alpha was mediated by inhibition of mitochondrial
      cytochrome c release. Thus, both Bcl-xL and Bcl-2 enhance survival of dendritic
      cells within the tumor microenvironment. In addition, mature DCs were more
      resistant to melanoma-induced apoptosis than immature dendritic cells. This
      finding suggests a stage-dependent sensitivity of DCs to tumor-induced cell
      death. We conclude that: (a) mature DCs might be more suitable for the use of
      cancer vaccination; and (b) Bcl-2 protein family members such as Bcl-xL and Bcl-2
      rescue DCs from tumor-induced premature apoptosis.

PMID- 11300500
TI  - Dendritic cells prolong tumor-specific T-cell survival and effector function
      after interaction with tumor targets.
AB  - Tumor specific CTLs are susceptible to tumor-mediated activated induced cell
      death (AICD) after target engagement. The presence of dendritic cells (DCs) at
      the site of tumors correlates with an improved prognosis in patients with a
      variety of histological tumor types. We examined whether DCs can modify the
      survival of tumor specific CTLs during encounter with tumor targets. HLA-A2+
      gp100-specific CD8+ CTLs were used as effectors against gp100+, A2+ melanoma FEM
      X, and Mel526 (A2-) targets as well as the melanoma target Mel397. Cytolytic
      assays and [3H]DNA fragmentation (JAM) assays were used to evaluate CTL
      specificity and tumor-mediated AICD, respectively. A functional assay, ARK
      (activity of rescued killer cells), was developed to measure cytolytic activity
      of surviving CTLs after a 12-h coincubation with tumor. In JAM assays, the CTLs
      proved more susceptible to apoptosis when exposed to the relevant tumors FEM-X
      and Mel526 than the irrelevant Mel397 (37 and 23% versus 3%; P < .001). The
      addition of human A2+ monocyte-derived immature DCs significantly (P < 0.001)
      limited this tumor-induced death of CTLs. In ARK assays, the presence of DCs
      decreased tumor-mediated suppression of CTLs, with increases in cytolytic
      function of CTLs reaching up to 2-fold. These findings suggest that DCs may play
      an important role during the effector phase of the immune response by enhancing
      the survival and function of CTLs in the tumor microenvironment.

PMID- 11300502
TI  - The effect of swallowing or rinsing alcohol solution on the mouth alcohol effect
      and slope detection of the intoxilyzer 5000.
AB  - Nine female and 21 male alcohol-free subjects introduced 10 mL of diluted gin
      (20% v/v alcohol) into their mouths under two conditions. The subjects either
      rinsed the alcohol for 10 s and then expectorated or immediately swallowed. They
      then provided breath samples into an Intoxilyzer 5000 at 5 and 10 min
      postadministration for both conditions. The mean Intoxilyzer results plus or
      minus one standard deviation (n = 30) were 0.091+/-0.051; 0.036+/-0.027; 0.014+/
      0.011, and 0.004+/-0.006 g/210 L for 5 min after rinsing, 5 min after swallowing,
      10 min after rinsing, and 10 min after swallowing, respectively. The percentages
      of times that mouth alcohol was correctly detected by the Intoxilyzer 5000 were
      90%, 66%, 62% and 30% for these conditions, respectively. Ten minutes after the
      introduction of alcohol into the mouth, 63% of the Intoxilyzer results were >
      0.010 g/210L after rinsing compared with only 7% after swallowing. The mouth
      alcohol effect is greater for rinsing than for swallowing alcohol.

PMID- 11300501
TI  - Acetylcodeine as a marker of illicit heroin in human hair: method validation and
      results of a pilot study.
AB  - Acetylcodeine (AC), which is an impurity of illicit heroin synthesis, was
      suggested as a marker of heroin abuse. A procedure for simultaneous quantitation
      of 6-monoacetylmorphine (6-MAM), which is the major metabolite of heroin,
      morphine, codeine, and AC in hair was developed. Fifty-milligram hair samples
      were incubated in 0.01 M HCl overnight at 60 degrees C. The resulting hydrolyzed
      solutions were extracted by an automated solid-phase extraction procedure and
      drugs were analyzed by gas chromatography-mass spectrometry in selected ion
      monitoring mode (SIM). This required prior derivatization with propionic
      anhydride. Different validation parameters, such as linearity, intra-assay
      accuracy, extraction recoveries, and limit of quantitation, were described.
      Seventy-three hair samples from heroin abusers and 43 hair samples from subjects
      who had completed a heroin-maintenance program were analyzed. AC was detected in
      92% of the first sample group and in only 12% of the second sample group. In the
      two groups, about 98% of AC-positive samples were found. These results prove that
      AC can be considered as a suitable marker of illicit heroin use, along with 6-MAM
      detection.

PMID- 11300503
TI  - Screening method for seventy psychoactive drugs or drug metabolites in serum
      based on high-performance liquid chromatography--electrospray ionization mass
      spectrometry.
AB  - A screening method for 70 psychoactive drugs or drug metabolites in human serum
      by solid-phase extraction with subsequent high-performance liquid chromatography
      and electrospray ionization mass spectrometry was developed. Enhanced selectivity
      of detection was obtained by collision-induced dissociation using two different
      skimmer voltages for the individual scan. The mass spectra and the retention
      times of the compounds were incorporated into a self-generated spectra library
      for identification in screening experiments. The detection limits were found to
      be between 0.1 and 5 ng/mL serum for the majority of the compounds when measured
      in the selected ion mode. Because of the very small serum concentrations and the
      rather low extraction yield, lysergide could not be detected in this way. It was
      demonstrated with 140 serum samples from alcohol-related traffic cases that this
      method is suitable for a routine screening in a forensic laboratory.

PMID- 11300504
TI  - General unknown screening in postmortem tissue and blood samples: a semi
      automatic solid-phase extraction using polystyrene resins followed by liquid
      liquid extraction.
AB  - The identification of general unknown poisons in complex biological materials
      like postmortem blood and tissue is a great challenge for the forensic
      toxicologist. Therefore, a screening procedure utilizing a semi-automatic work-up
      with an ASPEC system was developed. A broad range of different compounds can be
      isolated by using non-selective and generally applicable organic polymeric
      sorbents such as OASIS HLB or Isolute 101. Because colloidal solutions were
      applied to these sorbents, the denaturation of proteins, which can result in an
      irreversible loss of significant compounds by adsorption and occlusion, could be
      avoided. Because of the process of micellar chromatography followed by liquid
      liquid extraction of the crude extract, very clean fractions were obtained from
      such complex matrices as postmortem blood, liver, and brain samples. High
      recoveries (72-100%) and good day-to-day relative standard deviations (1-17%)
      could be achieved with both polymeric sorbents. The procedure paves the way for
      the identification of general unknown poisons in target organs and is therefore a
      useful tool in the field of forensic toxicology.

PMID- 11300505
TI  - Analytical methodology for the detection of benzodiazepine consumption in opioid
      dependent subjects.
AB  - Benzodiazepines are frequently abused by heroin users, but not all compounds have
      shown the same abuse liability. We developed an analytical method that was able
      to detect various benzodiazepine compounds in a single run. Enzymatically
      hydrolyzed urine underwent a liquid-liquid extraction procedure with
      chloroform/isopropanol (9:1) at pH 8-9 followed by a solid-liquid clean-up (Bond
      Elut TCA C18) to obtain appropriate extracts for HPLC analysis. Mobile phase
      composition was optimized by means of the linear solvation energy relationship
      methodology based on Reichardt's normalized solvatochromic parameter (E(T)N). The
      method was validated for the simultaneous detection and quantitation of
      alprazolam, alpha-hydroxyalprazolam, oxazepam, 7-aminoflunitrazepam,
      flunitrazepam, nordiazepam, lorazepam, and diazepam. The prevalence of
      benzodiazepine consumption in 229 opioid-dependent subjects on methadone
      maintenance treatment was 48%. Oxazepam and nordiazepam were the benzodiazepines
      most frequently recoved in urine samples. The prevalence of alprazolam use (40%)
      was higher than that of flunitrazepam (10%).

PMID- 11300506
TI  - Improved solid-phase extraction method for systematic toxicological analysis in
      biological fluids.
AB  - A method for the simultaneous qualitative and quantitative determination of drugs
      of abuse (opiates, cocaine, or amphetamines) and prescribed drugs (tricyclic
      antidepressants, phenotiazines, benzodiazepines, etc.) in biological fluids-
      blood, urine, bile, and gastric contents--was developed. This procedure involves
      solid-phase extraction with Bond-Elut Certify columns followed by analysis by gas
      chromatography-nitrogen-phosphorus detection (GC-NPD) and confirmation by gas
      chromatography-mass spectrometry (GC-MS), after derivatization, when necessary.
      Pretreatment was performed on all samples: sonication for 15 min plus enzymatic
      hydrolysis with beta-glucuronidase in urine. With respect to the internal
      standards, nalorphine and trihexylamine were used for basic substances,
      allobarbital for acidic drugs, and prazepam for benzodiazepines. Acidic and basic
      compounds were extracted from different aliquots of samples at different pH
      levels: 6-6.5 for the acidic and neutral and 8-8.5 for the basic and the
      benzodiazepines. Several areas of experimental design were considered in the
      process of method optimization. These included internal standards, pH,
      sonication, flow rate and washing solvents. It was found that systematic analysis
      could be reliably performed using optimized extraction conditions. The recovery
      rates for the compounds tested were always higher than 61.02%.

PMID- 11300507
TI  - Sweat testing of MDMA with the Drugwipe analytical device: a controlled study
      with two volunteers.
AB  - Rapid on-site tests for the analysis of drugs of abuse in unconventional
      specimens (e.g., sweat) have recently been developed. Two healthy volunteers
      familiar with the effects of methylenedioxymethamphetamine (MDMA) were given 100
      mg of the drug as a single oral dose. MDMA and its main metabolite 4-hydroxy-3
      methoxymethamphetamine (HMMA) were determined in plasma and urine by gas
      chromatography-mass spectrometry (GC-MS). MDMA was also investigated in sweat
      with the Drugwipe (an immunochemical strip test). Subjects' armpits were swabbed
      for 10 s at 0 time (predose) and at 2, 6, 8, 12, and 24 h after MDMA
      administration. MDMA consumption could be detected using Drugwipe at 2 h and for
      as long as 12 h after drug administration. However, in one of the volunteers, a
      faint color change appeared at 0 time, when plasma and urine tested negative for
      MDMA and did not disappear even 48 h later. Plasma concentrations of MDMA and
      HMMA measured by GC-MS peaked at 2-4 h, and values greater than 20 ng/mL for MDMA
      and of 40 ng/mL for HMMA were still detected at 24 h. Urine tested positive by GC
      MS for MDMA and HMMA in the 48-h collection period. These findings preliminarily
      support sweat testing with Drugwipe for monitoring MDMA use.

PMID- 11300508
TI  - A fatal case of serotonin syndrome after combined moclobemide-citalopram
      intoxication.
AB  - We present a case involving a fatality due to the combined ingestion of two
      different types of antidepressants. A 41-year-old Caucasian male, with a history
      of depression and suicide attempts, was found deceased at home. Multiple
      containers of medication, the MAO-inhibitor moclobemide (Aurorix), the SSRI
      citalopram (Cipramil), and the benzodiazepine lormetazepam (Noctamid) as active
      substance, as well as a bottle of whiskey were present at the scene. The autopsy
      findings were unremarkable, but systematic toxicological analysis (EMIT,
      radioimmunoassay, high-performance liquid chromatography-diode-array detection
      [HPLC-DAD], gas chromatography-nitrogen-phosphorus detection, and gas
      chromatography-mass spectrometry) revealed the following: ethanol (0.23 g/L
      blood, 0.67 g/L urine), lormetazepam (1.65 microg/mL urine), cotinine (0.63
      microg/mL blood, 5.08 microg/mL urine), caffeine (1.20 microg/mL urine),
      moclobemide (and metabolites), and citalopram (and metabolite). There upon, we
      developed a new liquid chromatographic separation with optimized DAD, preceded by
      an automated solid-phase extraction, for the quantitation of the previously
      mentioned antidepressive drugs. The results obtained for blood and urine,
      respectively, were as follows: Ro 12-5637 (moclobemide N'-oxide) not detected and
      424 microg/mL; Ro 12-8095 (3-keto-moclobemide) 2.26 microg/mL and 49.7 microg/mL;
      moclobemide 5.62 microg/mL and 204 microg/mL; desmethylcitalopram 0.42 microg/mL
      and 1.22 microg/mL; and citalopram 4.47 microg/mL and 19.7 microg/mL. The cause
      of death was attributed to the synergistic toxicity of moclobemide and
      citalopram, both antidepressants, which, by intentional or accidental combined
      ingestion, can produce a potentially lethal hyperserotoninergic state. Based on
      the history of the case and pharmacology of the drugs involved, the forensic
      pathologists ruled that the cause of death was multiple drug intoxication,
      resulting in a fatal "serotonin syndrome," and that the manner of death was
      suicide.

PMID- 11300509
TI  - The presence of gamma-hydroxybutyric acid (GHB) in postmortem biological fluids.

PMID- 11300510
TI  - Cobas Mira S endpoint enzymatic assay for plasma formate.
AB  - In methanol intoxication, increased levels of the metabolite formate are
      associated with metabolic acidosis and an increased risk for ocular and
      neurological dysfunction. A simple method for plasma formate measurement by
      adaptation of a manual enzymatic assay to a Cobas Mira S analyzer is presented.
      Six microliters of sample is incubated for 5 min with buffer containing
      nicotinamide-adenine dinucleotide. Fifteen microliters of a suspension of formate
      dehydrogenase is then added. Absorbance at 340 nm is measured every 25 s. The
      NADH produced when formate is oxidized is stoichiometric to the amount of
      formate. The method is sensitive, reproducible, and specific and has a broad
      measurement range. The frozen reagents are stable for at least six months, so the
      described method can be applied to irregular and semi-urgent requests. A recent
      case is reported.

PMID- 11300511
TI  - Quantitation of morphine and codeine in human urine using high-filed asymmetric
      waveform ion mobility spectrometry (FAIMS) with mass spectrometric detection.
AB  - Morphine and codeine have been identified and measured in a human urine matrix
      using high-field asymmetric waveform ion mobility spectrometry (FAIMS) in a
      tandem combination with electrospray ionization (ESI) and mass spectrometric (MS)
      detection. The addition of helium to the nitrogen carrier gas resulted in a
      substantial improvement in the sensitivity of the ESI-FAIMS-MS instrument for the
      determination of morphine and codeine. Limits of detection in human urine were 60
      ng/mL for morphine and 20 ng/mL for codeine with no clean-up, derivatization, or
      chromatographic separation of the sample prior to analysis.

PMID- 11300512
TI  - In vitro reaction of formaldehyde with fenfluramine: conversion to N-methyl
      fenfluramine.
AB  - Embalming is common, and it can create problems for the forensic scientist if a
      drug has been the cause death and this drug is also reactive toward the embalming
      fluid. Previous studies have focused on the tricyclic amines nortriptyline and
      desipramine. In the presence of formaldehyde, a typical component of embalming
      fluid, either of these two compounds can be rapidly converted to their methylated
      derivatives amitriptyline and imipramine, respectively. We have begun a larger
      project designed to determine the reactivity and reactions of a wide range of
      drugs with formaldehyde. We report here our results from fenfluramine, which,
      like the tricyclic amines, is reactive towards formaldehyde and is converted into
      its N-methyl derivative. The rate of conversion is dependent upon pH and
      formaldehyde concentration. Up to 100% conversion in 24 h was observed. In
      addition, we have also devised a simplified procedure for monitoring this process
      that may be useful for others working in this area. Finally, we note that the
      reactions of fenfluramine studied here and of amines in general with formaldehyde
      need to be considered when performing postmortem/postembalming forensic analysis.

PMID- 11300513
TI  - GC-MS determination of heroin metabolites in meconium: evaluation of four solid
      phase extraction cartridges.
AB  - A procedure for extraction of heroin and metabolites for gas chromatography-mass
      spectrometry (GC-MS) analysis of meconium specimens that would allow detection of
      these analytes at low levels was needed. Solid-phase extraction (SPE) cartridges
      were therefore evaluated for their effectiveness in sample preparation. Four
      different types of commercially available extraction cartridges were used.
      Heroin, 6-monoacetylmorphine (6-MAM), morphine, and codeine were extracted from
      meconium samples using these SPE cartridges and then simultaneously analyzed
      using GC-MS. In each case, the extraction efficiency, linearity range, limit of
      detection (LOD), limit of quantitation (LOQ), between-run precision, and within
      run precision were determined. Although satisfactory results were obtained with
      the four different types of SPE cartridges, best overall performance was observed
      using Clean Screen columns following the procedures outlined here. LODs as low as
      20 ng/g for codeine, 10 ng/g for morphine, and 2.5 ng/g for 6-MAM were obtained,
      and LOQs as low as 20 ng/g for codeine, 10 ng/g for morphine, and 5 ng/g for 6
      MAM were obtained. In all cases linearities were observed (r = > 0.99) for
      codeine, morphine, and 6-MAM over a wide concentration range (100-2000, 100-2000,
      and 5-100, respectively). At 50 ng/g codeine and morphine and 10 ng/g 6-MAM, the
      precision of analysis using these cartridges showed coefficients of variation
      ranging from 4.75% to 15.5%.

PMID- 11300514
TI  - Analysis of amphetamine and congeners in illicit samples by liquid chromatography
      and capillary electrophoresis.
AB  - Screening methods based on liquid chromatography (HPLC) and capillary
      electrophoresis (CE) have been developed for the identification and determination
      of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4
      methylenedioxymethamphetamine, and 3,4-methylenedioxyethylamphetamine in illicit
      tablets. Diethylpropione, (-)-ephedrine, and 3-amino-1-phenylbutane were also
      included in the study as amphetamino-related compounds. The HPLC-diode-array
      detection method involved on-line photochemical derivatization to enhance the
      selectivity of detection allowing amphetamines to be distinguished from related
      compounds such as diethylpropione (amfepramone). When the CE approach was
      adopted, two identification parameters (UV spectra and migration index) were used
      and the enantioresolution of the racemic amphetamines was achieved using
      hydroxypropyl-beta-cyclodextrin as chiral selector.

PMID- 11300515
TI  - Assessing the efficacy of perioperative carprofen administration in dogs
      undergoing surgical repair of a ruptured cranial cruciate ligament.

PMID- 11300516
TI  - Why automated differentials fall short.

PMID- 11300517
TI  - Chronic idiopathic pulmonary fibrosis in five dogs.
AB  - Five dogs presented with chronic and progressive pulmonary illness characterized
      by progressive dyspnea, exercise intolerance, and significant inspiratory
      crackles on auscultation. Radiographically, there was a widespread and diffuse
      interstitial lung pattern with varying degrees of bronchial involvement.
      Histopathological changes included thickened alveolar septa, interstitial
      fibrosis, and pneumocyte hyperplasia. Based on the clinical, radiographic, and
      histopathological changes, a diagnosis of idiopathic pulmonary fibrosis was made.
      Idiopathic pulmonary fibrosis is a chronic disease characterized by inflammation
      and fibrosis of the pulmonary interstitium and peripheral airspaces, which has
      been poorly characterized in the dog.

PMID- 11300518
TI  - Spontaneous lung lobe torsion in two pugs.
AB  - Two, young adult, male pugs presented for spontaneous left-cranial lung lobe
      torsions. Clinical signs associated with these two cases included increased
      weakness, increased respiratory effort, tachypnea, acute collapse, lethargy,
      anorexia, and cyanosis. The torsed lung lobes were excised using a
      thoracoabdominal stapling device without detorsing the lobes. Both dogs recovered
      uneventfully, and at least one year postoperatively, no clinical abnormalities
      were noted by their owners. Results of this report suggest that spontaneous lung
      lobe torsion in pugs occurs and should be a differential diagnosis for pugs with
      increased respiratory effort, tachypnea, nonproductive cough, acute collapse,
      cyanosis, and lethargy. Surgical excision may be curative.

PMID- 11300519
TI  - Neutropenia in dogs and cats: a retrospective study of 261 cases.
AB  - Case records of 232 dogs and 29 cats with neutropenia were reviewed to examine
      the spectrum of underlying etiologies causing the neutropenia. Six etiological
      categories included nonbacterial infectious disease; increased demand due to
      marked inflammation, bacterial sepsis, or endotoxemia; drug-associated
      neutropenia; primary bone-marrow disease; immune-mediated neutropenia; and
      diseases of unclear etiology. The largest single category associated with the
      development of neutropenia was nonbacterial infectious disease (e.g., feline
      leukemia virus [FeLV], feline immunodeficiency virus [FIV], histoplasmosis,
      cryptococcosis, and parvovirus), with parvovirus infection accounting for 47.1%
      of all cases. The least common (0.38%) cause was naturally occurring immune
      mediated neutropenia.

PMID- 11300520
TI  - A new technique for insertion of esophagostomy tubes in cats.
AB  - A new percutaneous insertion technique for esophageal feeding tubes in cats is
      presented. The technique has been successfully applied in 12 feline patients. The
      placement technique is relatively simple, takes approximately five minutes to
      perform, and requires a scalpel blade, a curved hemostat, and an applicator for
      the insertion of the feeding tube. In contrast to other esophageal tube placement
      techniques, the tube is inserted into the definitive aboral position in a one
      step procedure. Because of its shoehorn shape, the applicator allows the tube to
      be inserted into the esophagus safely and precisely. Placement of the tube in the
      midcervical area does not interfere with the function of the pharynx and avoids
      having the animal irritated by the presence of the tube. The chosen diameter of
      the tube is large enough to permit feeding of diluted, blended, commercial canned
      food. For the patients of this study, feeding was started after recovery from
      anesthesia, and tubes were removed without complications once the animals had
      started to eat voluntarily.

PMID- 11300521
TI  - Successful treatment of feline pancreatitis using an endoscopically placed
      gastrojejunostomy tube.
AB  - A cat with pancreatitis, diagnosed using abdominal ultrasonography, fine-needle
      aspirate cytopathology, and increased concentration of serum trypsin-like
      immunoreactive substance, was treated successfully using jejunal alimentation
      provided through a percutaneous gastrojejunostomy tube. This method of jejunal
      feeding is less technically difficult, less stressful for the patient, and has
      fewer complications than surgically placed jejunostomy tubes. Nutritional support
      with jejunal feeding is superior to total parenteral nutrition, as it maintains
      gut integrity, decreases septic complications, and may reduce exogenous insulin
      requirements. The methods of tube insertion and maintenance, and the
      physiological advantages over other feeding methods are described.

PMID- 11300522
TI  - Serum alpha 1-acid glycoprotein concentration in cats with lymphoma.
AB  - Serum alpha 1-acid glycoprotein (AGP) concentrations were evaluated in nine cats
      with lymphoma. Twenty-five healthy cats were used as controls. Blood samples were
      obtained from cats with lymphoma prior to induction chemotherapy, one week
      following induction, at complete response, and at monthly intervals. The median
      pretreatment AGP concentration for the nine cats with lymphoma was significantly
      higher than the median AGP concentration for the 25 control cats. Remission serum
      AGP concentration was not significantly different from the pretreatment AGP
      concentration in the cats with lymphoma. Serum AGP concentrations provided no
      useful information regarding response or survival in cats with lymphoma.

PMID- 11300523
TI  - Primary cardiac rhabdomyosarcoma in a cat.
AB  - A seven-year-old domestic shorthair (DSH) cat was presented with anorexia and
      dyspnea. Pleural-pericardial effusion was detected with thoracic radiographs and
      echocardiography. Echocardiography demonstrated a large, soft-tissue mass in the
      right ventricular wall, protruding both into the pericardial space and into the
      right ventricle. Postmortem examination findings included a large mass in the
      right ventricular wall and multiple smaller masses on the external surface of the
      left ventricle and on the internal surface of the pericardium. Results of the
      histopathological and immunohistochemical examinations of the masses were
      consistent with rhabdomyosarcoma. This is the first reported case of primary
      cardiac rhabdomyosarcoma in the cat.

PMID- 11300524
TI  - Clinical assessment of a chemosensitivity assay as a treatment planning tool for
      dogs with cancer.
AB  - This study evaluated the clinical utility of a commercially available
      chemosensitivity assay. In the first part of the study, tumor tissues from dogs
      with various malignancies were tested, and the dogs were treated with a
      mitoxantrone/cyclophosphamide combination protocol. Tumor response was evaluated
      and compared to the predicted response. Assay results were not a significant
      predictor of clinical response to chemotherapy or of survival time. In the second
      part of the study, assay results were used to direct therapy in dogs with
      refractory lymphoma. There was no significant correlation (p equals 0.323)
      between predicted response and case outcome.

PMID- 11300525
TI  - Radial carpal bone fracture in dogs.
AB  - In a retrospective study, 11 radial carpal bone (RCB) fractures in nine dogs were
      studied. Chronic lameness was reported in all dogs. Reduced range of motion and
      soft-tissue swelling of the carpal joints were clinical signs seen most
      frequently. Three common fracture patterns were identified: oblique fracture with
      a large medial fragment, sagittal fracture with a small medial fragment, and
      comminuted fracture. Radial carpal bone sclerosis and carpal osteoarthritis were
      identified in all dogs. Pancarpal arthrodesis was used to manage 55% of the RCB
      fractures in this report. Although RCB fracture is not associated with obvious
      trauma, the fracture mechanism is unknown.

PMID- 11300526
TI  - Alveolar mucosal approach to the canine nasal cavity.
AB  - A nine-year-old, intact female Afghan hound was presented for evaluation of an
      intermittent, mucopurulent, unilateral nasal discharge with a three-year
      duration. Radiographs showed the ipsilateral canine tooth within the rostral
      nasal cavity. The tooth was removed through an alveolar mucosal rhinotomy. There
      has been no recurrence of the nasal discharge or complications associated with
      the surgical procedure during the 20-month follow-up period.

PMID- 11300527
TI  - Bilateral overlapping mucosal single-pedicle flaps for correction of soft palate
      defects.
AB  - The clinical outcomes of bilateral overlapping single-pedicle flaps used for
      repair of congenital cleft of the soft palate in 10 animals (nine dogs and one
      cat) are reported. Six animals had concurrent cleft of the hard palate repaired
      using a previously described mucoperiosteal flap technique. Animals ranged from
      one to 13 months of age at surgery, with follow-up ranging from two to 12 months.
      Healing was uncomplicated in all cases and provided excellent functional results.

PMID- 11300528
TI  - Surgical correction of a congenital preputial and penile deformity in a dog.
AB  - An 11-month-old, intact male Great Pyrenees was presented for recurrent,
      nonpainful accumulation of suppurative fluid within the prepuce. Surgical
      exploration revealed a continuation of the urethral mucosa with the cutaneous
      epidermis of the prepuce, thus creating a closed preputial cavity surrounding the
      penis where fluid could accumulate. A persistent frenulum and a previously
      undescribed tissue remnant connecting the dorsal and distal aspects of the penis
      to the dorsal wall of the prepuce were also present. Surgical correction of the
      preputial and penile deformity, along with correction of the resulting
      paraphimosis and pendulous prepuce that became apparent following the initial
      surgery, are discussed.

PMID- 11300529
TI  - Limited approach to the right flank for placement of a duodenostomy tube.
AB  - A new enterostomy tube placement technique is described for provision of
      nutrients into the duodenum. Placement of the duodenostomy tube (d-tube) is
      performed through a limited right flank approach under sedation and local
      anesthesia. Seven client-owned animals (three dogs and four cats) requiring
      enteral nutritional support were selected for d-tube placement. Patients were fed
      via the d-tube for two to 28 days. Complications included discomfort when
      manipulating and exteriorizing the duodenum, discomfort with bolus feedings,
      local cellulitis, and tube site infection. All complications resolved without
      further incident. This technique should be considered in patients that are not
      good candidates for prolonged general anesthesia or esophageal or gastric
      feeding, or patients being mechanically ventilated.

PMID- 11300530
TI  - Effective contaminant detection networks in uncertain groundwater flow fields.
AB  - A mass transport simulation model tested seven contaminant detection-monitoring
      networks under a 40 degrees range of groundwater flow directions. Each monitoring
      network contained five wells located 40 m from a rectangular landfill. The 40-m
      distance (lag) was measured in different directions, depending upon the strategy
      used to design a particular monitoring network. Lagging the wells parallel to the
      central flow path was more effective than alternative design strategies. Other
      strategies allowed higher percentages of leaks to migrate between monitoring
      wells. Results of this study suggest that centrally lagged groundwater monitoring
      networks perform most effectively in uncertain groundwater-flow fields.

PMID- 11300531
TI  - Stabilization/solidification of MSW incineration residues from facilities with
      different air pollution control systems. Durability of matrices versus
      carbonation.
AB  - This paper discusses the stabilisation/solidification process with Portland
      cement applied to municipal solid waste incineration residues. Two types of
      residues were considered: fly ash (FA) produced in an electrostatic precipitator,
      and air pollution control (APC) residues from a semi-dry scrubber process. Cement
      pastes with different percentages of FA and APC residues were characterised
      according to their physical properties, the effect of the hydration products and
      their leaching behaviour. Portland pastes prepared with APC residues showed a
      rapid setting velocity in comparison with setting time for those pastes
      substituted with FA residues. Portland cement hydration was retarded in FA
      pastes. Leaching test results showed that heavy metals (such as Zn, Pb and Cd)
      and sulphates are immobilised within the paste, whereas chlorides are only
      partially retained. The carbonation process increases the leachability of S04(2-)
      and heavy metals such as Zn and Cr.

PMID- 11300532
TI  - Leaching characteristics of paraffin waste forms generated from Korean nuclear
      power plants.
AB  - Leaching tests of paraffin waste forms including boric acid, cobalt, strontium
      and cesium were performed to investigate the leaching characteristics of paraffin
      waste forms which had been generated in Korean nuclear power plants. The leaching
      tests were conducted according to ANSI/ANS-16.1 test procedure and the cumulative
      fractions leached (CFLs) of boric acid, cobalt, strontium and cesium were
      obtained. The compressive strength before and after the leaching test was
      measured for various waste forms with different mixing ratios of boric acid to
      paraffin. It was observed that boric acid and other nuclides immobilized within
      paraffin waste forms were congruently released and the leaching rates were
      influenced by reacted layer depth as the dissolution reaction progressed. A
      shrinking core model based on the diffusion-controlled dissolution kinetics was
      developed in order to simulate the test results. The CFLs and the leaching rates
      were well expressed by the shrinking core model and the cross-sectional view of
      specimen after the test demonstrated the applicability of this model with the
      shrinking dissolution front to the leaching analysis of paraffin waste forms.

PMID- 11300533
TI  - A study of the corrosion products of mild steel in high ionic strength brines.
AB  - The corrosion layer on steel surfaces that formed after exposure to waste
      isolation pilot plant (WIPP) brines under anoxic conditions was characterized for
      chemical composition, thickness and phase composition. The chemical composition
      of the corrosion layer was determined both by X-ray photoelectron spectroscopy
      (XPS) and by chemical analysis of acid solutions used to remove the corrosion
      layer. Atomic force microscopic (AFM) images indicated that the brine-corroded
      surface layer shows extensive granulation along the contours of the steel surface
      that is characteristic of sharp polishing marks. The corrosion layer seemed to be
      porous and could be dissolved and detached in dilute hydrochloric acid. The
      corrosion layer appears to be composed of iron oxides with some ionic
      substitutions from the brines. The 77 K Mossbauer spectrum recorded for iron
      powder leached under similar conditions indicated the corrosion layer was
      comprised principally of green rust.

PMID- 11300534
TI  - Decomposition of hazardous organic materials in the solidification/stabilization
      process using catalytic-activated carbon.
AB  - The application of a catalytic-activated carbon to the
      solidification/stabilization (S/S) process for immobilization of phenol and 2
      chlorophenol and catalytic decomposition was investigated. The effect of the
      catalytic-activated carbon, in amounts of 0.25-1% (by dry sand wt.), on the
      leaching of phenol and 2-chlorophenol was studied. H2O2 was added as a source of
      oxygen in the amounts of 1 or 5%, with respect to liquid solution weight.
      Toxicity characteristic leaching procedure (TCLP) leaching tests showed that
      adding the catalytic-activated carbon to the S/S matrix significantly reduced the
      leachability of both phenol and 2-chlorophenol. Only trace amounts of phenol were
      found in the leaching solution, while the concentration of 2-chlorophenol was
      below the detection limit of the gas chromatography (GC). Without addition of the
      catalytic-activated carbon, 87% of the phenol and 92% of the 2-chlorophenol
      leached. Additional tests on TCLP leachate solutions using GC-mass spectrometry
      indicated the existence of simple, less hazardous, hydrocarbons, including
      alcohol. Catalytic-activated carbons treated with phenol in the presence of H2O2
      were also analyzed using time of flight-secondary ion mass spectroscopy (TOF
      SIMS). Results indicate that the phenol aromatic ring was broken by the catalytic
      reaction.

PMID- 11300535
TI  - Description and identification of difficulties arising from the application of a
      cleaning process in operating conditions for the treatment of components used on
      liquid metal fast reactors (LMFR). A technical designed approach to avoid these
      situations.
AB  - The cleaning process is one of the major maintenance operation for liquid metal
      fast reactors (LMFRs), both in operation and in their decommissioning stage.
      Russian and French cleaning processes are briefly described, including problems
      which have arisen during the processes. It appears that the cause of these
      problems is always connected to bad draining of the component, resulting in a
      vigorous reaction between vapour or liquid water and the bulk of sodium. From
      this discussion, the paper makes major recommendations for the efficient and safe
      cleaning of sodium wetted components, and proposes several processes which should
      be developed in order to deal with difficult situations, for example the removal
      of large amounts of undrainable sodium.

PMID- 11300536
TI  - Development and application of a sorption data base for the performance
      assessment of a radwaste repository.
AB  - A sorption data base (SDB) provides readily available data for the performance
      assessment of a radwaste repository when site-specific and/or reference data are
      needed. The software developed at KAERI, SDB-21C, is a graphic user interface
      (GUI) program that provides efficient and user-friendly tools for evaluating
      large amount of sorption data. In addition, the most comprehensive sorption data
      base that contains about 11,000 NEA data and 2,000 KAERI data was compiled in the
      program. Besides the simple Kd approach, a parametric model and its compiled data
      sets are also included in the SDB-21C. In order to evaluate the versatility of
      SDB-21C, several applications were performed for relevant hypothetical
      situations.

PMID- 11300537
TI  - Solvent cleaning of pole transformers containing PCB contaminated insulating oil.
AB  - In 1989, it was discovered that the recycled insulation oil in pole transformers
      for electric power supply was contaminated with trace amounts of polychlorinated
      biphenyls (PCBs; maximum 50 mg-PCB/kg-insulation oil). In order to remove the
      PCBs from transformer components using n-hexane as a solvent, we investigated the
      relationship between progressive stages of dismantling and cleaning results. The
      results are summarized as follows: (1) Based on the cleaning test results, we
      made an estimate of the residual PCB amount on iron and copper components. By
      dismantling the test pole transformers into the "iron core and coil portion" and
      cleaning the components, we achieved a residual PCB amount that was below the
      limit of detection (0.05 mg-PCB/kg-material). To achieve a residual PCB amount
      below the limit of detection for the transformer paper component, it was
      necessary to cut the paper into pieces smaller than 5 mm. We were unable to
      achieve a residual PCB amount below the limit of detection for the wood
      component. (2) Compared to Japan's stipulated limited concentration standard
      values for PCBs, the results of the cleaning test show that cleaning iron or
      copper components with PCBs only on their surface with the solvent n-hexane will
      satisfy the limited concentration standard values when care is taken to ensure
      the component surfaces have adequate contact with the cleaning solvent.

PMID- 11300538
TI  - Uptake of dyes by a promising locally available agricultural solid waste: coir
      pith.
AB  - The adsorption of rhodamine-B and acid violet by coir pith carbon was carried out
      by varying the parameters such as agitation time, dye concentration, adsorbent
      dose and pH. The adsorption followed both Langmuir and Freundlich isotherms. The
      adsorption capacity was found to be 2.56 mg and 8.06 mg dye per g of the
      adsorbent for rhodamine-B and acid violet, respectively. Adsorption of dyes
      followed first order rate kinetics. Acidic pH was favorable for the adsorption of
      acid violet and alkaline pH was favorable to rhodamine-B. Desorption studies
      showed that alkaline pH was favorable for the desorption of acid violet and
      acidic pH was favorable for the desorption of rhodamine-B.

PMID- 11300539
TI  - An analysis of UK waste minimization clubs: key requirements for future cost
      effective developments.
AB  - The UK waste strategy is based upon use of the best practicable environmental
      option (BPEO), by those making waste management decisions. BPEO is supported by
      the use of the waste hierarchy, with its range of preferable options for dealing
      with waste, and the proximity principle, where waste is treated/disposed of as
      close to its point of origin as possible. The national waste strategy emphasizes
      the key role of waste minimization and encourages industry, commerce and the
      public to move towards sustainable waste management practice for economic and
      environmental reasons. Waste minimization clubs have been used, since the early
      1990s, to demonstrate to industry/commerce that reducing waste production can
      lead to significant financial savings. There have been around 75 such clubs in
      the UK and they receive support from a wide range of agencies, including the
      Environmental Technology Best Practice Program. The early Demonstration Clubs had
      significant savings to cost ratios, e.g. Aire and Calder at 8.4, but had very
      high costs, e.g. Aire and Calder at 400,000 pounds. It is acknowledged that the
      number of clubs will have to be approximately doubled in the next few years so as
      to have an adequate coverage of the UK. There are at present, marked regional
      variations in club development and cognizance needs to be taken, by facilitators,
      of the need for extensive coverage of the UK. Future clubs will probably have to
      operate in a financially constrained climate and they need to be designed to
      deliver significant savings and waste reduction at low cost. To aid future club
      design, final reports of all projects should report in a standard manner so that
      cost benefit analysis can be used to inform facilitators about the most effective
      club type. rights reserved.

PMID- 11300540
TI  - Thermal behaviour of chromium electroplating sludge.
AB  - Galvanic sludge is classified as a hazardous waste and incineration is one of the
      techniques used for its treatment. The aim of this work is to study the thermal
      behavior of a galvanic sludge which contains only chromium as a restriction
      metal. Simultaneous DTA/TG coupled with mass spectrometer tests were performed to
      characterize the thermal behavior of the sludge. Besides thermal analysis, sludge
      samples were heated in a specially designed furnace and these samples were
      submitted to X-ray diffraction. Vapor from the heated sludge was condensed and
      the particles were analyzed by EDS microprobe coupled in a scanning electron
      microscope. The slag formed after the calcination of the galvanic sludge was
      mainly composed of a mixture of calcium phosphate and fluoride. and minor
      concentrations of metals. A total weight loss of 34% was observed. The greatest
      part of this weight loss corresponds to CO2, H2O and SO2. H2O is liberated in the
      temperature range of 500-1,250 degrees C. CO2 in the range of 500-750 degrees C
      and SO2 near 1,000 degrees C. Chromium evaporation was not observed in relevant
      quantities, about 99.6% of the Cr remained incorporated in the slag.

PMID- 11300542
TI  - The role of global negative self-evaluations in the influence of body weight on
      weight and eating concerns.
AB  - The aim of this study was to test a model based on the assumption that a social
      comparison-process of body mass index could lead to weight and eating concerns by
      lowering self-evaluation. Three hundred and ninety-five girls from five age
      cohorts (in grades five through nine at the time of data collection) participated
      in a questionnaire-based study. Support for a model where global negative self
      evaluations played a mediating role was found among the oldest girls who
      perceived slimness norms among their peers. Among girls not perceiving a norm of
      thinness, and among younger girls perceiving such a norm, the model found no
      support. The proposed model gives an explanation of how the dynamic process of
      social norms of thinness, body weight and self-evaluation, can cause some girls
      to become concerned about their body weight.

PMID- 11300544
TI  - Letter writing as a therapeutic tool.
AB  - A novel method of family therapy for persons suffering from eating disorders,
      therapeutic letter writing (TLR), is presented. The protocol used for letter
      writing, its advantages and limitations, and a variety of applications are
      reviewed. The concept of TLR grew out of the study of narrative therapy, and was
      strongly influenced by ideas of Lorraine Wright and Maureeen Leahey about nurses
      and families, as well as the work of W.R. Miller around stages of change. This
      article will review: the process of TLR; therapeutic uses of eating disorders
      linked to TLR, including those relevant to families divided by distance or
      understanding; and the advantanges and disadvantages of TLR. Finally, a case
      study is discussed.

PMID- 11300543
TI  - Exercise and eating disorder symptoms among young females.
AB  - BACKGROUND: In various settings, eating disorder symptoms have been linked to
      physical activity. METHODS: A random sample of 726 females, aged 17-23 years,
      responded on a self-administered questionnaire. "High level exercisers" (HiEx)
      were defined as subjects exercising > or =6 sessions/week, > or =1 h/session.
      "Exercisers with obligatory attitudes" (ObEx) were those obtaining a result above
      the 95th percentile on a composite score of obligatory exercise items. These
      groups were compared to controls regarding composite scores of eating disorder
      symptoms and other symptoms. RESULTS: While HiEx did not, ObEx obtained a
      significant result at the p<0.001 level regarding the score for body image
      problems, recurrent weight-reducing attempts, bingeing and post-prandial impulses
      to vomit. ObEx was also associated with symptoms related to stress and in
      particular with a high level of general activity coupled with perfectionistic
      ambitions. CONCLUSIONS: Eating disorder symptoms in young females seem to be
      associated with obligatory attitudes to exercise rather than with exercise
      quantity.

PMID- 11300545
TI  - Prevention: a psychoanalytic viewpoint.
AB  - Psychoanalysis teaches that a symptom should not be regarded as an accident
      occurring during the development of one individual or another, but basically the
      effect of his or her "predisposition" to a disorder before any interaction with
      the environment takes place. Prevention seems to assume the form of a scientific
      and technical expedient aimed at the optimisation of life and the repression of
      pain. If it is not possible to prevent dreams, slips of the tongue and other
      parapraxes, in the same way we cannot prevent the other inventions of the
      unconscious from which a psychic illness, such as anorexia, bulimia, distortion
      of or obsession with the body image etc., emerges. The ethics of the unconscious
      subject does not surrender to the perverse mirages of illness, nor, however, to
      the normalising appearances of health. It simply claims the right not to be
      distorted, to be understood, but not made uniform. What could be the form of
      prevention that those who have chosen to work with the psyche are destined for?

PMID- 11300541
TI  - The eating attitudes test: twenty-five years later.
AB  - This manuscript reviews the literature involved with the Eating Attitudes Test
      (EAT), first developed in the late 1970s as a self-report, indicative of the
      symptoms of eating disorders. The EAT has good psychometric properties of
      reliability and validity, and reasonable sensitivity and specificity for the
      eating disorders, but very low positive predictive value because eating disorders
      are relatively uncommon. In addition they exist on a continuum, because of denial
      and social desirability, the results of a self-report instrument may be affected.
      A very large literature has documented the use of the EAT in a variety of
      cultures. It is used to screen eating disturbances in general as the first part
      of a two-part diagnostic screen, as an ability to compare across groups and to
      measure change between groups and over time.

PMID- 11300546
TI  - Heat in the treatment of patients with anorexia nervosa.
AB  - The paper presents the results of heat treatment in three cases of anorexia
      nervosa (AN), in which marked overactivity and/or strenuous exercising were
      prominent clinical features. Heat was supplied in three ways: continuous exposure
      to a warm environment, wearing a thermal waistcoat, and sauna baths in an
      infrared cabin. The outcomes went far beyond what had been expected, as the
      disappearance of hyperactivity was followed by progressive recovery.

PMID- 11300547
TI  - Subtyping women with bulimia nervosa along dietary and negative affect
      dimensions: a replication in a treatment-seeking sample.
AB  - Recent cluster-analysis studies of women with bulimia nervosa (BN) have suggested
      two subtypes, a pure dietary subtype and a mixed dietary-negative affect. We
      aimed to replicate the subtyping findings in a clinical study group of 48 adult
      women with BN. Cluster analyses revealed a dietary-negative affect subtype (56%
      of cases) and a pure dietary subtype (44% of cases). The dietary-negative affect
      subtype was characterized by significantly greater eating-related attitudinal
      psychopathology and associated psychological disturbance. Our findings suggest
      that severe restraint is a central feature of BN and that affective disturbance,
      which occurs in roughly half of cases, is associated with greater eating-related
      attitudinal psychopathology and psychological symptomatology.

PMID- 11300548
TI  - Oral cavity and oropharynx.
AB  - Cross-sectional imaging has become an essential element in the evaluation of
      disease processes involving the oral cavity and oropharynx. This article is an
      overview of the anatomy and typical pathology of the these areas. The
      radiologist, working in conjunction with the physical examination and the
      clinical evaluation of a careful head and neck surgeon, can provide information
      that is critical to the treatment of patients with oral cavity and oropharyngeal
      disease.

PMID- 11300549
TI  - The squaric acid aggregate in mordenite investigated by Raman spectroscopy.
AB  - A more detailed investigation of the squaric acid aggregate within mordenite was
      undertaken with the use of Raman spectroscopy. The previous reported
      investigation was limited to the carbonyl stretching region in the IR. In the
      present work the entire region from 500 to 2000 cm(-1) was investigated,
      revealing rather substantial vibrational shifts of the oxocarbon ring modes in
      the aggregate. Comparison of such shifts with those observed for the squaric acid
      (H2Sq)/4,4'-bipyridine (Bipy) charge transfer (CT) complex reveals that the
      interaction is much stronger in the aggregate, a clear effect of the restrict
      geometry. On the other hand, the shifts observed for the CO stretching modes are
      rather modest. The comparison of the ring modes present in the Raman spectra of
      squaric acid, potassium hydrogen squarate, potassium squarate, H2Sq/Bipy and
      squaric acid aggregate in mordenite strongly suggests that in the latter hydrogen
      bonded species are present.

PMID- 11300550
TI  - A study of the possible and preferred site of protonation in 7-methyl-1,5,7
      triazabicyclo[4,4,0]dec-5-ene by vibrational spectroscopic methods.
AB  - The normal co-ordinate analysis have been carried out for 7-methyl-1,5,7
      triazabicyclo[4,4,0]dec-5-ene (MTBD) and its three possible protonated tautomeric
      forms. The calculations and measured infrared (IR) spectra are consistent with a
      tautomeric species in which the proton is attached to an imine nitrogen atom.

PMID- 11300551
TI  - Structural chemistry of some new azo complexes.
AB  - The preparation of 2-thiouracil (H2L) and its 5-(2-thiazolylazo)thiouracil (H2L')
      complexes with CoII, NiII, CuII, ZnII and CdII are reported. The new complexes
      have been characterized by elemental analyses, solid reflectance, infrared
      spectra and magnetic susceptibilities. These measurements suggest that, the
      ligand is bound to the metal ion through nitrogen and/or sulphur atom behaving as
      mono- or bidentate ligand. Thermal decomposition studies of these metal complexes
      are explained to give more information on the structure of the investigated
      chelates. On the basis of the v(OH) bending frequencies and the insolubility of
      the complexes in common organic solvents, polymeric structures have been
      proposed.

PMID- 11300552
TI  - Photophysical process of hexadecyl 4-biphenylamino benzoate.
AB  - The photophysical properties of hexadecyl 4-biphenylamino benzoate (HBAB), the
      molecule of which possesses a polar end composed of donor (triphenylamino group)
      and acceptor (ester group) and a long non-polar alkyl tail, have been carefully
      studied in different conditions. The results show that the twisted intramolecular
      charge transfer (TICT) emission is given in polar solvents at room temperature
      and intramolecular charge transfer (ICT) emission is given at 77 K. These can be
      supported by the solvent effect, temperature effect and the quenching process.

PMID- 11300553
TI  - In-situ spectroscopic investigations of the redox behavior of poly(indole-5
      carboxylic-acid) modified electrodes in acidic aqueous solutions.
AB  - The oxidation of electrochemically grown poly(indole-5-carboxylic-acid) (P5CO2H)
      and its spectroscopic properties have been studied by in-situ
      spectroelectrochemical techniques. The purpose of this paper is to characterize
      the different modifications on the P5CO2H backbone, induced by the
      electrochemical oxidation in aqueous acidic solution. We have identified, on the
      basis of Raman spectra, the vibrational modes associated with neutral and
      oxidized segments of polymer. It was shown that at least three chemically and
      optically different species (perhaps other products too) are produced in
      different potential regimes upon oxidation of this polymer. The results obtained
      also indicate that the molecular properties of this conducting polymer are better
      revealed by in-situ resonant spectra than by ex-situ infrared and Raman studies.

PMID- 11300554
TI  - Studies on charge transfer properties from mixture of Schiff base and zinc
      complex in Langmuir-Blodgett film by UV-vis absorption and Fourier transform
      infrared spectroscopy.
AB  - A novel mixed Langmuir Blodgett (LB) film based on a 1:1 (molar ratio) mixture of
      a non-amphiphile complex (Et4N)2[Zn(dmit)2] (H2dmit = 4,5-dimercapto-1,3-dithiole
      2-thione) and Schiff base amphiphile 2,4-dihydroxy-N-octadecylbenzylideneamine
      (SBC18) was constructed and characterized by Fourier transform infrared (FTIR)
      spectra and UV-vis electronic absorption spectra. After iodine was doped in situ,
      magnitude of charge transfer increases, which was demonstrated by FTIR and UV-vis
      absorption spectral analysis.

PMID- 11300555
TI  - EPR of Cu(II)-doped seven-coordinate inclusion compounds, M(stpy)3(NO3)2 x
      1/2stpy (M = Cd(II) and Zn(II), stpy = trans-4-styrylpyridine): low symmetry
      effects in admixture of ground states.
AB  - Single crystal EPR of Cu(II)-doped low symmetry pentagonal bipyramidal Werner
      type clathrate inclusion complexes of Cd(stpy)3(NO3)2 x 1/2stpy(1) and
      Zn(stpy)3(NO3)2 x 1/2stpy(2) (stpy = trans-4-styrylpyridine) is reported. The
      spin Hamiltonian parameters are found to be orthorhombic with g33 = 2.298, g22 =
      2.108, g11 = 2.066, A33 = 107.3, A22 = 54.4 and A11 = 23.1 x 10(-4) cm(-1) for 1
      and g33 = 2.292, g22 = 2.111, g11 = 2.067, A33 = 107.5, A22 = 54.7 and A11 = 22.9
      x 10(-4) cm(-1) for 2. Angular variation studies for both 1 and 2 suggest that
      the Cu(II) ions are substitutionally incorporated in the host lattices. The
      magnitude of Cu(II) hyperfine coupling constant (A33) in both 1 and 2 are found
      to be low, in comparison to those of the pure Cu(II) complex, indicative of low
      symmetry for the substitutional sites in accordance with the crystal data. Such
      large reductions in Cu(II) hyperfine coupling are explicable in terms of a mixed
      d(x2 - y2)/dz2 ground state and delocalization of unpaired spin density onto the
      ligands.

PMID- 11300556
TI  - Spectroscopic studies of metal complexes with redox-active hydrogenated Schiff
      bases.
AB  - Synthesis and spectroscopic (IR, UV-visible, ESR) characterization of metal(II)
      complexes M(Lx')2, (where M = Co(II), NI(II), VO(II), Pd(II), Lx' = L1', L2', L3'
      are monoanion of unsubstituted, 5-Cl and 5-Br substituted-2-hydroxybenzylamine)
      with redox-active N-(3,5-ditert-butyl-4-hydroxyphenyl)-2-hydroxybenzylamine
      ligands as well as radical species generated from these compounds by the
      oxidation with PbO2 are reported. ESR studies indicate that the VO(Lx')2 and
      Ni(Lx')2 complexes, in opposite to their salicylaldimine precursors, are more
      readily oxidized with lead dioxide and results in the formation of the
      indophenoxyl type stable radical. The formed radical species are very similar to
      each other and quite different from those of the salicylaldimine analogous
      according to their g-factors and hyperfine coupling constants. The nine line
      radical spectra observed in the oxidation of Co(Lx')2, on standing under vacuum,
      gradually converted to the signals characteristic of the low-spin Co(II) (g(x,y)
      = 2.276, g(z) = 1.998, A(xy)Co = 122.7 G, A(z)Co = 150 G) and radical containing
      Co(III) intermediate with g(x,y) = 2.015, A(xy)Co = 4.66 G, g(z) = 1.989, A(z)Co
      = 10 G were also observed.

PMID- 11300557
TI  - Description of band wings and band area measurement.
AB  - Applicability of the Gaussian and Lorentzian function to spectral bands is
      analyzed, and some problems of band area determination are discussed.

PMID- 11300558
TI  - Experimental and theoretical vibrational study of isatin, its 5-(NO2, F, Cl, Br,
      I, CH3) analogues and the isatinato anion.
AB  - Effects of 5-R substitution (R = NO2, F, Cl, Br, I, CH3) and N-deprotonation on
      the 4000-400 cm(-1) region of the low temperature FT IR spectrum and the
      molecular structure of solid isatin are investigated. Harmonic IR spectra and
      molecular geometries of the 5-R isatins (except for Br and I analogues) are
      calculated at the HF/6-31G(d, p) level and compared with the experimental solid
      state data. In general, substitution has small effect on the molecular structure
      and the IR spectrum of isatin. The v(CO) triplet in the IR spectra of isatin and
      its 5-substituted analogues is resulted by vibrational splitting of the out-of
      phase CO stretching, v(op)[(CO)2]. While the frequency of the v(op)[(CO)2] mode
      is relatively less affected by 5-substitution and mainly depends on the
      substituent mass, the frequency of the in-phase stretching, v(ip)[(CO)2], is
      strongly sensitive to both mass and electronic properties of the substituent.
      Substitution at C5 has relatively greater influence on the electron density and
      the force constant of the amide than on the ketone carbonyl group. Strong
      electron-donors shorten and stabilize the unusually long alpha-dicarbonyl CC
      bond, while electron-accepting groups tend to stretch this bond further. N
      Deprotonation brings to elongation of the five membered-ring along the N
      C(CO(ketone)) vector and expansion of the bonds within the alpha-dicarbonyl part.
      Theoretical v(CO) frequency of isatin is lowered for about 180 cm(-1) upon
      conversion into isatinato ion. Harmonic vibrational analysis reveals that only
      the highest-frequency v(CO) mode of the isolated isatinato anion can be
      considered good group vibration for empirical assignments in spectra of solid
      isatinates. Owing to the solid-state influences on the v[(CO)2] modes, no
      reliable spectra structure correlations could be established from the present
      experimental spectroscopic data.

PMID- 11300559
TI  - Structure of exciplexes: solvent and temperature dependences of charge transfer
      character.
AB  - The influence of temperature on the efficiency of fluorescence of the encounter
      complex (A- ...D+)* in intermolecular electron transfer starting from neutral
      precursors has been studied. In contrast to what is generally assumed,
      fluorescence emission of the exciplexes is found to be thermally activated. The
      systems studied here consist of N,N-dimethylaniline (DMA), and tributylamine
      (TBA) as electron donors and anthracene (An) as electron acceptor. This study has
      proved that the two exciplexes behave differently with temperature.

PMID- 11300560
TI  - Role of dipole moment of solvents in formation and stabilization of the TICT
      states in Coumarin 445 under nitrogen laser excitation.
AB  - In this paper we report the observation of dual Amplified Spontaneous Emission
      (ASE) from solutions of 7-ethylamino-4-methyl coumarin dye (Coumarin 445) in
      certain solvents such as n-butyl acetate, dioxane etc. when pumped by high power
      nitrogen laser. The two ASE bands appear to be from two different excited species
      (ICT and TICT conformation) one of which is the precursor of the other. The
      spectral characteristics of dye Coumarin 445 depend upon the solvent environment.
      The TICT coumarin photoisomers, which form exciplexes with the solvent molecules,
      have enough gain to produce amplified spontaneous emission even when there is
      apparently no detectable fluorescence. The behaviour of this dye in the excited
      state is studied by measuring the small signal gain and variation of the gain
      slope with temperature in different solvents. It is observed that polarity of the
      solvent plays a more dominant role in formation and stabilization of TICT states.

PMID- 11300561
TI  - Photophysical processes of 1,3-dicarbazolypropane.
AB  - The photophysical processes of 1,3-dicarbazolypropane (DCZP), which possesses two
      fluorogen, carbazoly, and one carbonic chain composed of three carbon atoms, were
      studied. The formation of intermolecular excimer, intramolecular excimer and
      triple exciplexes have been investigated in the system of DCZP and 1,4
      dinitrilebenzene (DNB) with steady state fluorescence spectroscopy. The
      experimental results show that with the addition of DNB into the lower
      concentration solution of DCZP in benzene, the fluorescence of intramolecular
      excimer of DCZP, (D-D)*, is quenched while the ((D-D)A)* type triple exciplex
      (one molecule of DCZP with one molecule of DNB) is formed and with the addition
      of DNB into higher concentration solution of DCZP, the formation of (DDA)* type
      triple exciplex (two molecules of DCZP with one molecule of DNB) is also
      confirmed.

PMID- 11300562
TI  - PM3, AM1, MNDO and MINDO3 semi-empirical IR spectra simulations for compounds of
      interest for Titan's chemistry: diazomethane, methyl azide, methyl isocyanide,
      diacetylene and triacetylene.
AB  - Four semi-empirical methods (PM3, AM1, MNDO and MINDO3) have been tested to find
      the best auxiliary tool for the gas chromatography/Fourier transform IR
      spectroscopy/mass spectrometry (GC/FTIR/MS) identification of five compounds of
      interest for Titan's atmospheric chemistry as test compounds: diacetylene,
      triacetylene, diazomethane, methyl azide, methyl isocyanide. Of the four methods,
      MINDO3 can be considered as the most appropriate method to facilitate the
      identification of such and similar compounds, since (1) the simulated IR spectra
      best match the experimental spectra for four compounds of five studied; and (2)
      MINDO3 provides the best linearity between the calculated and experimental
      frequencies (correlation coefficient of 0.995; a scaling factor of 0.84 can be
      applied to afford better correspondence between the calculated and experimental
      wavenumbers). None of the semi-empirical methods tested is able to predict (even
      approximately) infrared band intensities, and therefore a spectral intensity
      pattern.

PMID- 11300563
TI  - A comparative vibrational and NMR study of cis-cinnamic acid polymorphs and trans
      cinnamic acid.
AB  - The IR and Raman spectra of the two polymorphic forms (58 degree- and 68 degree
      forms) of cis-cinnamic acid were measured, and the spectral differences discussed
      on the basis of the crystal structures of the two forms. The IR bands related to
      the COOH group differ in the frequencies and band shape, reflecting differences
      in the hydrogen bonding between the two modifications. These spectra were
      compared with those of trans-cinnamic acid. The IR, Raman, and NMR spectra of the
      isotopic compounds, including the deuterated and 13C analogs of the cis and trans
      acids, were also recorded in the solid state and in solution to confirm the
      spectral assignments.

PMID- 11300564
TI  - Fragment mode analysis and its application to the vibrational normal modes of
      boron trichloride-ammonia and boron trichloride-pyridine complexes.
AB  - A method for expressing quantitatively the vibrational normal modes of a molecule
      in a basis set consisting of the normal vibrations (plus translations and
      rotations) of its constituent fragments is presented. The method is illustrated
      by describing the vibrational modes of BCl3-NH3 and BCl3-pyridine electron donor
      acceptor complexes in terms of motions of BCl3 and either NH3 or pyridine. These
      complexes show examples of mixing between modes located on different fragments,
      mixing between modes of one fragment due to symmetry lowering, and the
      transformation of six fragment translations/rotations into vibrations of the
      complex. Although perturbation theory has been proposed to explain such examples
      of mode mixing, calculations imply that interactions between fragments of both
      complexes are too strong for perturbation theory to be generally applicable. In
      addition, the transformation of fragment rotations and/or translations into
      vibrations of the composite molecule will always occur and cannot be understood
      in detail by using perturbation theory. For the BCl3-pyridine complex, a band
      observed at 1107 cm(-1) is re-assigned as a combination of C-H in-plane bending
      and a ring-breathing mode of the pyridine fragment.

PMID- 11300565
TI  - Optimization of force constants with an Urey-Bradley force field avoiding normal
      mode crossings.
AB  - We present a method that simplifies the refinement of force constants in normal
      mode calculations and makes the results more reliable. The method avoids normal
      mode crossings by constraining the force constants during refinement. It was
      tested with pyrrole, imidazole, benzene, pyridine, pyrimidine, aniline and
      adenine using a Urey-Bradley force field. The global error of the frequency fit
      for these molecules was 0.61%. The method reproduced with fewer parameters the
      accuracy of similar calculations of the single ring aromatic compounds. It
      improved the accuracy and isotopic shifts of previous empirical calculations of
      adenine by 40%. The C-C and C-N stretchings differed by less than 7% from the
      values of force constant-bond length empirical relations.

PMID- 11300566
TI  - Electron transfer compatible molecular design of benzothiophene-acetophenone
      bichromophores: a theoretical approach.
AB  - Computational work has been done for a bichromophore (4MBA) comprising a donor 4
      methoxy-benzo[b]thiophene (4MBT) and an acceptor molecule p-chloro-acetophenone
      (pclA) linked together by a HC=CH bond which shows large hyperpolarizability. The
      charge transfer in this bichromophoric system is computed by semiemperical
      theoretical calculation. Ground state and excited state dipole moment difference
      of the bichromophore 4MBA indicates a large electron transfer probability.

PMID- 11300567
TI  - Surface-enhanced Raman spectra study of metal complexes of N-D-glucosamine beta
      naphthaldehyde and glycine and their interaction with DNA.
AB  - Copper(II), zinc(II), cobalt(II) and cobalt(III) complexes of N-D-glucosamine
      beta-naphthaldehyde (C17H19O6N, NG) and glycine were synthesized. The four novel
      metal complexes, Cu(II)C19H28O11N2(CuGNG), Zn(II)C19H24O9N2 (ZnGNG),
      Co(II)C19H28O11N2(Co(II)GNG) and Co(III)C21H29O12N2(Co(III)GNG) were
      characterized by means of infrared (IR), electronic absorption spectroscopy and
      NMR etc. The surface-enhanced Raman spectra of the four complexes and their
      interaction with DNA were studied. By comparison of the surface-enhanced Raman
      spectra (SERS), the information of the four complexes' SER active sites and
      adsorption orientation were obtained. Combined with fluorescence spectra of
      Ethidium bromide (EthBr) DNA system, we concluded that none of the four complexes
      intercalate into DNA and that the presence of the glycine ligand lowered the
      anticancer activity of NG series complexes.

PMID- 11300568
TI  - Spectroscopy and predissociation of the 3A2 electronic state of ozone 16O3 and
      18O3 by high resolution Fourier transform spectrometry.
AB  - A high resolution Fourier transform spectrometry analysis of the rotational
      structure of the 2(0)1 absorption bands of the 3A2<--X1A1 Wulf transition for the
      isotopomers 16O3 and 18O3 of the ozone molecule is presented. These bands are
      very intense compared to the 0(0)0 bands but the predissociation is so strong
      that the main sub-bands appear as continuous contours. Isolated lines and band
      contour methods are used together to analyse these two rovibrational bands. The
      lines corresponding to the F2 component are generally the most intense and
      isolated. Our data sets for the (0 1 0) level of the 3A2 state are limited to
      about 102 weakly or unperturbed rotational lines for the 2(0)1 of 16O3 in the
      range 9620-10,140 cm(-1) and 123 weakly or unperturbed rotational lines for the
      same band of 18O3. Using for each of them the well-defined ground state
      parameters, we obtained a standard deviation of about 0.035 cm(-1) in the fit to
      the lines for 16O3 and 0.027 cm(-1) in the case of 18O3. The rotational constants
      A, B and C, the three rotational distortion terms deltaK, deltaJK and deltaJ, the
      spin-rotation constants a0, a and b have been successfully calculated for 16O3
      and 18O3 while the spin-spin constants were fixed to their respective values
      obtained for the origin bands. As is the case for the 0(0)0 band, we have a
      partial agreement with the isotopic laws for the rotational constants. The
      geometrical parameters of the (0 1 0) level of 3A2 state for the two isotopomers
      are close, r = 1.357 A, theta = 100.7 degrees for 18O3 and r = 1.352 A and theta
      = 100.0 degrees for 16O3. The origin of the 2(0)1 band of 18O3 is red shifted by
      7.06(4) cm(-1) with respect to 16O3 2(0)1 band and the two bending mode quanta
      are, respectively, 528.99(9) and 501.34(7) cm(-1). A preliminary qualitative
      analysis of the predissociation is given in the particular case of the F2 spin
      component of 16O3 for 0(0)0 and 2(0)1 bands by the measurement of shifts of
      positions of some rovibrational levels and the evolution of predissociation
      broadenings in (Q)Q2 branches. We justify the existence of perturbations in the
      rovibrational levels of 3A2 state through different interaction types: with the
      dissociation continuum of the same electronic state or with high vibrational
      repulsive or weakly bound levels of the ground state.

PMID- 11300569
TI  - Vibrational analysis of iron and zinc phosphate conversion coating constituents.
AB  - The FT-MIR/FT-FIR and NIR-FT-Raman spectra of orthorhombic alpha-Zn3(PO4)2 x 4H2O
      (alpha-hopeite) and monoclinic Zn2Fe(PO4)2 x 4H2O (phosphophyllite), including
      deuterated samples, have been measured in the polycrystalline state at room
      temperature and below. The distribution of vibrational levels was related to the
      results of complete unit-cell group analyses. The number of uncoupled OD
      stretching modes of alpha-hopeite (isotopically dilute samples) strongly exceeds
      that expected from the number of hydrogen positions of the structure reported. In
      contrast, unequivocal assignment of the four hydrogen bonds of phosphophyllite
      has been performed. The distortion of the phosphate tetrahedra, as revealed from
      both site group and unit-cell group splitting of the PO stretching modes, is
      found to be almost equal in both compounds, in accordance with the identical
      tetrahedral linkage scheme.

PMID- 11300570
TI  - Complexes of Al(III) with 3'4'-dihydroxy-flavone: characterization, theoretical
      and spectroscopic study.
AB  - Complex formation between aluminium chloride and 3'4'-dihydroxyflavone
      (3'4'diOHF) in methanol has been studied by UV-visible and Raman spectroscopies
      combined with quantum chemical calculations. Job's method of continuous variation
      and the molar ratio method were applied to ascertain the stoichiometry
      composition of the chelate in pure methanol. A 1:1 complex was indicated by both
      the methods. Geometry optimizations of free and complexed molecules by AMI and
      DFT methods show that structural modifications of the ligand, induced by
      complexation, are minor, and are localized on the chelating site. The good
      agreement between experimental and theoretical electronic spectra of both
      3'4'diOHF and complex confirm the structural models. The great similarities
      between Raman spectra of the free and complexed form constitute an another proof
      of the absence of pronounced electronic and geometric changes, and notably
      demonstrate that the quinoidal form induced by the deprotonation of the two
      hydroxyl groups does not participate in the 3'4'diOHF complex structure. Whereas
      no complexation occurs in acidic medium, complexes of high stoichiometry are
      formed in alkaline medium. (Al(3'4'diOHF)2)- and (Al(3'4'diOHF)3)3- species are
      observed in methanol in the presence of sodium acetate or sodium methanoate.

PMID- 11300571
TI  - Raman spectroscopy of potassium acetate-intercalated kaolinites at liquid
      nitrogen temperature.
AB  - Raman microscopy has been used to study low and high defect kaolinites and their
      potassium acetate intercalated complexes at 298 and 77 K. Raman spectroscopy
      shows significant differences in the spectra of the hydroxyl-stretching region of
      the two types of kaolinites, which is also reflected in the spectroscopy of the
      hydroxyl-stretching region of the intercalation complexes. Additional bands to
      the normally observed kaolinite hydroxyl stretching frequencies are observed for
      the low and high defect kaolinites at 3605 and 3602 cm(-1) at 298 K. Upon cooling
      to liquid nitrogen temperature, these bands are observed at 3607 and 3604 cm(-1),
      thus indicating a weakening of the hydrogen bond formed between the inner surface
      hydroxyls and the acetate ion. Upon cooling to liquid nitrogen temperature, the
      frequency of the inner hydroxyls shifted to lower frequencies. Collection of
      Raman spectra at liquid nitrogen temperature did not give better band separation
      compared to the room temperature spectra as the bands increased in width and
      shifted closer together.

PMID- 11300573
TI  - The face in the crowd revisited: a threat advantage with schematic stimuli.
AB  - Schematic threatening, friendly, and neutral faces were used to test the
      hypothesis that humans preferentially orient their attention toward threat. Using
      a visual search paradigm, participants searched for discrepant faces in matrices
      of otherwise identical faces. Across 5 experiments, results consistently showed
      faster and more accurate detection of threatening than friendly targets. The
      threat advantage was obvious regardless of whether the conditions favored
      parallel or serial search (i.e., involved neutral or emotional distractors), and
      it was valid for inverted faces. Threatening angry faces were more quickly and
      accurately detected than were other negative faces (sad or "scheming"), which
      suggests that the threat advantage can be attributed to threat rather than to the
      negative valence or the uniqueness of the target display.

PMID- 11300572
TI  - Chronic and temporary distinct expectancies as comparison standards: automatic
      contrast in dispositional judgments.
AB  - In 4 studies, the authors examined whether making outcome expectancies distinct
      resulted in their use as comparison standards and, consequently, in contrastive
      dispositional inferences for a target's behaviors. The expectancies examined were
      based on either chronic future-event expectancies (Study 1) or temporary,
      manipulated expectancy standards (Studies 2-4). Analyses revealed that when
      contextual expectancies were distinct or separable from target information,
      participants' dispositional judgments were contrasted from them under cognitive
      load and overcorrected (assimilated to them) under no load. These effects were
      mediated by participants' behavior categorizations. Evidence suggestive of a
      proceduralized form of correction for task difficulty and an effortful awareness
      based correction for the effects of expectancies also were found. Results are
      examined in light of recent models of the dispositional inference process.

PMID- 11300574
TI  - The semantic--procedural interface model of the self: the role of self-knowledge
      for context-dependent versus context-independent modes of thinking.
AB  - How do independent and interdependent self-construals affect cognition? The
      authors proposed the semantic-procedural interface model, which distinguishes 2
      such mechanisms. In addition to semantic differences, different procedural modes
      of thinking are associated with independent and interdependent self-construals.
      Independent self-definitions coincide with the tendency to process stimuli
      unaffected by the context in which they appear. Interdependent self-construals
      facilitate context-bounded thinking (i.e., processing stimuli by paying attention
      to their relation to the given context). With semantic-free dependent variables,
      4 experiments showed independence-primed participants to exhibit higher degrees
      of context independence than did interdependence-primed participants. The results
      are discussed with reference to their potential explanations for cross-cultural
      differences.

PMID- 11300575
TI  - Abstract and concrete self-evaluative goals.
AB  - Assuming that people often hold the abstract goal of acquiring accurate feedback
      but recognize that acquiring favorable feedback can make the self-evaluative
      process more comfortable, the authors posited that low-level construals (of how
      action is performed) would elicit greater self-enhancement motivation than would
      high-level construals (of why action is performed). Individuals chronically using
      low-level construals had greater interest in downward social comparison (DSC) and
      less interest in negative feedback (NF; Studies 1 and 3). Decreases in temporal
      distance (which foster low-level construals) also elicited greater interest in
      DSC and less interest in NF (Studies 2 and 4). The latter effect was explained by
      participants' aversion to inconvenience (Study 5) and not by approach-avoidance
      conflict (Study 6). These results suggest that the level of abstraction at which
      people construe self-evaluative situations can influence their feedback
      preferences.

PMID- 11300576
TI  - The role of attachment in responses to victims of life crises.
AB  - Attachment effects on affect, cognitions, and behavior during an interaction with
      a confederate who purportedly had cancer and whose attachment orientation had
      been manipulated in a prior context were examined among 241 participants. Results
      supported theoretically derived predictions: Participant anxious attachment
      predicted anxiety, participant avoidant attachment predicted supportiveness, and
      participant avoidant attachment interacted with confederate avoidant attachment
      to predict rejection. Results suggest (a) the importance of attachment in
      predicting interpersonal responses in a nonromantic stressful context, (b) that
      anxious attachment is an important predictor of anxiety in a situation with
      implicit support demands, (c) that avoidant attachment is a potentially important
      predictor of the likelihood of supportive responses to victims, and (d) that
      attachment orientation can be successfully manipulated in experimental studies of
      attachment.

PMID- 11300577
TI  - Accuracy and bias in the perception of the partner in a close relationship.
AB  - Partners in close relationships can be both accurate and biased in their
      perceptions of each other. Moreover, sometimes a bias can lead to accuracy. The
      authors describe a paradigm for the simultaneous measurement of accuracy and bias
      in 2-person relationships. One prevalent bias in close relationships is assumed
      similarity: Does the person think that his or her partner sees the world as he or
      she does? In a study of 238 dating and married heterosexual couples, the authors
      found evidence for both bias and accuracy: the bias effects were considerably
      stronger, especially when the measure was linked to the relationship. They found
      little or no evidence for gender differences in accuracy and bias.

PMID- 11300578
TI  - Bad news transmission as a function of the definitiveness of consequences and the
      relationship between communicator and recipient.
AB  - There is ample evidence suggesting (e.g., A. Tesser & S. Rosen, 1975) that people
      are reluctant to transmit bad news. Research on rumors, on the other hand,
      suggests that people sometimes are less reluctant to transmit bad news. It is
      argued that differences between the 2 lines of research include the
      definitiveness of the consequences of the news and the relationship between
      communicator and recipient. The influence of these 2 factors on news transmission
      was investigated in 3 experiments. Results showed that bad news with indefinite
      consequences was transmitted more often than bad news with definite consequences
      and that both kinds of bad news were transmitted more often if the recipient was
      a friend rather than a stranger. Differences in feelings of moral responsibility
      to transmit the news largely accounted for both effects. The 2 factors did not
      affect the likelihood of good news transmission.

PMID- 11300579
TI  - Can one ever be too wealthy or too chaste? Searching for nonlinearities in mate
      judgment.
AB  - In 3 studies, the authors searched for nonlinearities as possible clues to
      context-sensitive mechanisms involved in mating decisions. Participants judged
      targets' sexual desirability, marital desirability, or social status on the basis
      of information about income or number of past sexual partners. Because one cannot
      know in advance where nonlinearities occur or measure all values of independent
      variables, a "zoom and focus" method was used. The authors began by sampling a
      wide range of values, followed by successively more focused examination of
      potentially interesting regions. Across studies, income and desirability were
      linked exponentially, particularly for male targets and marriage partners. Sexual
      partners and desirability were sometimes linked nonmonotonically, with more
      partners first increasing, then decreasing, desirability. The authors discuss how
      nonmonotonic functions may suggest competing underlying processes.

PMID- 11300580
TI  - Compensatory conviction in the face of personal uncertainty: going to extremes
      and being oneself.
AB  - Study 1 participants' self-integrity (C. M. Steele. 1988) was threatened by
      deliberative mind-set (S. E. Taylor & P. M. Gollwitzer, 1995) induced
      uncertainty. They masked the uncertainty with more extreme conviction about
      social issues. An integrity-repair exercise after the threat, however, eliminated
      uncertainty and the conviction response. In Study 2, the same threat caused
      clarified values and more self-consistent personal goals. Two other uncertainty
      related threats, mortality salience and temporal discontinuity, caused similar
      responses: more extreme intergroup bias in Study 3, and more self-consistent
      personal goals and identifications in Study 4. Going to extremes and being
      oneself are seen as 2 modes of compensatory conviction used to defend against
      personal uncertainty. Relevance to cognitive dissonance and authoritarianism
      theories is discussed, and a new perspective on terror managenment theory (J.
      Greenberg, S. Solomom, & T. Pyszczynski, 1997) is proposed.

PMID- 11300581
TI  - Daily interpersonal experiences, context, and alcohol consumption: crying in your
      beer and toasting good times.
AB  - The authors explored a multidimensional view of drinking, whereby social and
      solitary drinking represent distinct behaviors associated with positive and
      negative experiences, respectively. Using daily diary methodology and multilevel
      analytic strategy, the authors examined, over 30 days, the within-person
      association of negative and positive experiences and alcohol consumption in
      different contexts and focused on interpersonal experiences. On days with more
      negative interpersonal experiences, participants engaged in more solitary
      drinking (i.e., drinking at home and alone), whereas on days with more positive
      interpersonal experiences they drank more in social contexts. The authors also
      demonstrated that individuals high on neuroticism drank more in solitary contexts
      on days with more negative interpersonal experiences, relative to those with
      lower neuroticism. These findings lend support to models linking daily drinking
      motivation and context-dependent drinking behavior.

PMID- 11300582
TI  - A 2 X 2 achievement goal framework.
AB  - A 2 x 2 achievement goal framework comprising mastery-approach, mastery
      avoidance, performance-approach, and performance-avoidance goals was proposed and
      tested in 3 studies. Factor analytic results supported the independence of the 4
      achievement goal constructs. The goals were examined with respect to several
      important antecedents (e.g., motive dispositions, implicit theories,
      socialization histories) and consequences (e.g., anticipatory test anxiety, exam
      performance, health center visits), with particular attention allocated to the
      new mastery-avoidance goal construct. The results revealed distinct empirical
      profiles for each of the achievement goals; the pattern for mastery-avoidance
      goals was, as anticipated, more negative than that for mastery-approach goals and
      more positive than that for performance-avoidance goals. Implications of the
      present work for future theoretical development in the achievement goal
      literature are discussed.

PMID- 11300583
TI  - Tissue harmonic imaging techniques: physical principles and clinical
      applications.
AB  - Tissue harmonic imaging (THI) is a new gray-scale sonographic technique that
      improves image clarity. Harmonics form within the insonated tissue as a
      consequence of nonlinear sound propagation. Imaging with endogenously formed
      harmonics means that the distorting layer of the body wall is traversed only once
      by the harmonic beam--during echo reception. Both image contrast and lateral
      resolution are improved in harmonic mode compared with conventional (fundamental
      mode) sonography. This article summarizes the physics and various implementations
      of harmonic imaging mode, and reviews the clinical applications that have emerged
      to date.

PMID- 11300584
TI  - Ultrasound contrast harmonic imaging of abdominal organs.
AB  - Ultrasound contrast agents consist of microbubbles, which are the most effective
      acoustic backscatters. The interaction between the insonating ultrasound beam and
      the microbubbles is very complex and basic understanding of their behavior under
      various sound fields has been fundamental to the development of improved methods
      of visualizing and displaying the contrast agents. Although echo enhancers have
      been under development for a long time, their clinical applications have been
      limited to enhancing the Doppler signals in difficult cases. However, recent
      advances in harmonic imaging and the development of new tissue-specific contrast
      agents stand to broaden the scope of ultrasound diagnostic potential beyond
      simply rescuing failed Doppler examinations. This article reviews the current and
      potential applications of ultrasound contrast harmonic imaging in the abdomen.

PMID- 11300585
TI  - Sonographic contrast agents in vascular imaging.
AB  - The use of ultrasound contrast agents for peripheral vascular imaging has not
      been adapted widely worldwide and remains experimental in the United States.
      Nevertheless, there is considerable interest in contrast agents, because they
      potentially might offer substantial benefits for peripheral vascular imaging.
      This article reviews the status of ultrasound contrast agents. It includes a
      thorough discussion of the types of agents that are available or are under
      development and an assessment of the desirable properties of an ideal contrast
      agent. The interaction of these agents with ultrasound is considered next,
      including consideration of the advantages of harmonic imaging with contrast.
      Finally, the potential clinical benefits of contrast, as revealed by the authors
      experience and published data, are reviewed for a variety of cerebral,
      peripheral, and abdominal vascular applications. These include the carotid
      arteries, transcranial Doppler, extremity arteries and veins, the renal arteries,
      and hepatic vessels.

PMID- 11300586
TI  - New developments in the sonographic assessment of ovarian, uterine, and breast
      vascularity.
AB  - Recent developments in ultrasound have presented new opportunities for assessing
      tissue vascularity and blood flow with ultrasound. These new methods include 3D
      imaging, power Doppler sonography, a variety of harmonic imaging techniques,
      ultrasound contrast agents, electronic compounding, and pulse sequencing methods
      that improve the signal-to-noise relationship as well as structural conspicuity.
      By using these technological advances, it is now possible to assess macroscopic
      blood flow in organs and tumors, and to assess changes in flow and vascularity
      that occur in response to therapeutic efforts. This review article describes and
      illustrates the concepts and methods used to evaluate vascularity and blood flow
      in tissues with ultrasound. It describes some of the potential clinical
      applications of these new techniques in the ovary, uterus, endometrium, adnexal
      vessels, and breast.

PMID- 11300587
TI  - Real-time spatial compound imaging: application to breast, vascular, and
      musculoskeletal ultrasound.
AB  - Real-time spatial compound imaging (SonoCT) is an ultrasound technique that uses
      electronic beam steering of a transducer array to rapidly acquire several (three
      to nine) overlapping scans of an object from different view angles. These single
      angle scans are averaged to form a multiangle compound image that is updated in
      real time with each subsequent scan. Compound imaging shows improved image
      quality compared with conventional ultrasound, primarily because of reduction of
      speckle, clutter, and other acoustic artifacts. Early clinical experience
      suggests that real-time spatial compound imaging can provide improved contrast
      resolution and tissue differentiation that is beneficial for imaging the breast,
      peripheral blood vessels, and musculoskeletal injuries. Future development of
      real-time spatial compound imaging will help address the bulk of general imaging
      applications by extending this technology to curved array transducers, tissue
      harmonics, panoramic imaging, and three-dimensional sonography.

PMID- 11300588
TI  - Extended field-of-view ultrasound.
AB  - When ultrasound became a clinical reality in the 1970s, extended field of view
      was the only form of imaging available because all ultrasound images were created
      with articulated arm scanners that encompassed the area of interest in its
      entirety. With the advent of high-quality real-time imaging in the 1980s, the
      extended field of view was lost, and with it went an important diagnostic
      component as well as an important means of communicating diagnostic findings to
      referring clinicians. Through the magic of computer technology, extended field of
      view imaging is back! Extended field of view images can now be created very
      easily and conveniently, in real time. The convenience and accuracy of real-time
      imaging is maintained while important anatomical perspectives are added. This
      article reviews the status of real-time extended field of view sonography. The
      technical details as well as the clinical relevance of this method are
      summarized. The day-to-day clinical utility of extended field of view imaging is
      liberally illustrated.

PMID- 11300589
TI  - Ultrasound virtual endoscopic imaging.
AB  - Volume data acquisition, three dimensional (3D) imaging, and multiplanar
      reformatting have become widely used for computed tomography (CT) and magnetic
      resonance imaging (MRI). As an extension of this technology, virtual endoscopic
      visualization of hollow organs has become a reality that is now finding its way
      into clinical CT practice. The same methods of computer processing as are used
      for CT and MRI can be applied to an ultrasound (US) volume image data set with
      the same potential output; namely, 3D, multiplanar, and virtual endoscopic
      images. The use of this image processing technology for US applications has
      lagged behind the CT and MRI applications, but considerable progress in applying
      these methods to US has occurred in recent years. As a result, US virtual
      endoscopic imaging now can be performed on a clinical basis by using standard US
      instruments and commercially available computer software. The use of newer US
      imaging methods, such as tissue harmonic and power Doppler imaging, has enhanced
      the potential for US virtual endoscopy. This article reviews the technology of US
      virtual endoscopy. In addition, our preliminary experience of using this method
      for abdominal and vascular diagnosis is described. Finally, we speculate on
      technical improvements and potential applications that are likely in the future.

PMID- 11300590
TI  - Ultrasound imaging in three and four dimensions.
AB  - Three-dimensional (3D) reconstruction of ultrasound images was first demonstrated
      nearly 15 years ago, but only now is becoming a clinical reality. In the
      meantime, methods for 3D reconstruction of CT and MRI images have achieved an
      advanced state of development, and 3D imaging with these modalities has been
      applied widely in clinical practice. 3D applications in ultrasound have lagged
      behind CT and MRI, because ultrasound data is much more difficult to render in
      3D, for a variety of technical reasons, than either CT or MRI data. Only in the
      past few years has the computing power of ultrasound equipment reached a level
      adequate enough for the complex signal processing tasks needed to render
      ultrasound data in three dimensions. At this point in time, the clinical
      application of 3D ultrasound is likely to advance rapidly, as improved 3D
      rendering technology becomes more widely available. This article is a review of
      the present status of 3D ultrasound imaging. It begins by comparing the
      characteristics of CT, MRI, and ultrasound image data that either make these data
      amenable or not amenable to 3D reconstruction. The article then considers the
      technical features involved with acquiring an ultrasound 3D data set and the
      mechanisms for reconstructing the images. Finally, the article reviews the
      literature that is available regarding clinical application of 3D ultrasound in
      obstetrics, ultrasound, the abdomen, and blood vessels.

PMID- 11300591
TI  - Pathogenesis of single right coronary artery and pulmonic stenosis in English
      Bulldogs.
AB  - English Bulldogs are the most common breed to have pulmonic stenosis. Previous
      studies showed that this congenital heart abnormality in Bulldogs frequently is
      caused by a circumpulmonary left coronary artery originating from a single right
      coronary artery. Fetal anasarca also occurs often in Bulldogs and might represent
      congestive heart failure, but the cause is unknown. To determine if fetal
      anasarca is associated with a coronary anomaly and pulmonic stenosis, major
      coronary arteries were studied in 6 bulldog puppies with fetal anasarca. Five of
      the puppies had normal coronary arteries, and this led to the conclusion that
      fetal anasarca usually is not associated with major coronary abnormalities or
      pulmonic stenosis. The 6th puppy had single right coronary artery with
      circumpulmonary left coronary artery and moderate subvalvular pulmonic stenosis.
      Serial section histology suggests that the underlying cause of this syndrome is
      malformation of the left aortic sinus (of Valsalva) and inversion of the proximal
      segment of the left main coronary artery.

PMID- 11300592
TI  - Efficacy of a single oral dose of isorsorbide 5-mononitrate in normal dogs and in
      dogs with congestive heart failure.
AB  - Isosorbide 5-mononitrate (5-ISMN) was evaluated in normal dogs and dogs with
      congestive heart failure (CHF) in a randomized, blinded, and placebo-controlled
      study. Equilibrium blood pool imaging was used to detect changes in regional
      blood volume distribution. Six normal dogs were administered placebo, 2, 3, and 4
      mg/kg 5-ISMN PO on separate days with a 1-week washout period between randomized
      dosings. Six dogs with CHF were administered placebo or 4 mg/kg 5-ISMN on
      separate days with a 1-week washout period between randomized dosings. Data were
      collected at baseline and at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240
      minutes after dosing. Measured variables included indirect arterial blood
      pressure (BP), heart rate (HR), packed cell volume (PCV), scintigraphic count
      rates for normal dogs, and scintigraphic count rates for CHF dogs. Blood for
      plasma 5-ISMN concentration determination was collected at 60 minutes.
      Scintigraphic counts were corrected for decay and expressed as a percentage of
      the whole. No differences were detected in BP, HR, PCV, thoracic blood volume
      percentage (TBVP), or abdominal blood volume percentage (ABVP) between placebo
      and 5-ISMN in normal dogs at any dose. No differences were detected in TBVP or
      ABVP between placebo and 5-ISMN in dogs with CHF Plasma 5-ISMN concentration
      exceeded the minimum therapeutic concentration in all dogs and at all doses 60
      minutes after drug administration. Equilibrium blood pool imaging failed to
      detect a shift in blood volume with oral 5-ISMN administration at any dose tested
      in normal dogs and dogs with CHF, despite adequate drug absorption. On the basis
      of the results of this study, 5-ISMN may not be beneficial in the treatment of
      dogs with CHF.

PMID- 11300593
TI  - Canine motor neuron disease: clinicopathologic features and selected indicators
      of oxidative stress.
AB  - Hereditary canine spinal muscular atrophy (HCSMA) is an inherited motor neuron
      disease affecting a kindred of Brittanies. We have examined the clinicopathologic
      abnormalities in 57 animals with HCSMA, including 43 affected adult dogs and 14
      homozygote pups. We also measured selected biochemical indices of oxidative
      stress: serum vitamin E (alpha-tocopherol) and Se concentrations; serum
      concentrations of Cu, Zn, Mg, and Fe; and total superoxide dismutase and
      glutathione peroxidase activities in red blood cells. Dogs with HCSMA had the
      following abnormalities: regenerative anemia, hypoglobulinemia, hypochloremia,
      and abnormally high creatine kinase and liver alkaline phosphatase activities.
      Serum Cu concentration was significantly (P = .01) increased in adult dogs with
      HCSMA compared to control dogs. Serum vitamin E concentrations tended to be lower
      in adult dogs with HCSMA compared to controls, and were significantly (P = .01)
      lower in homozygote pups compared to control pups.

PMID- 11300594
TI  - Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs.
AB  - Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the
      axial skeleton were reviewed to determine prevalence of metastasis and survival
      associated with this neoplasm. All dogs were treated with more than 1 mode of
      therapy including palliative radiation (n = 12), definitive radiation (n = 8),
      surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies.
      Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all
      dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed
      (retriever versus purebred versus mixed-breed survival was 100, 182, and 264
      days, respectively) and radiation therapy protocol (survival in dogs treated with
      palliative radiation therapy versus those treated with definitive radiation
      therapy was 79 and 265 days, respectively) were significantly related to survival
      (P < .05). Prevalence of metastasis and median survival for large-breed dogs with
      axial skeleton OSA seems to be similar to that reported for large-breed dogs with
      appendicular skeleton OSA. Definitive radiation therapy may have a role in the
      treatment of axial skeleton osteosarcoma.

PMID- 11300595
TI  - Single agent chemotherapy with doxorubicin for feline lymphoma: a retrospective
      study of 19 cases (1994-1997).
AB  - Medical records of 21 cats with confirmed lymphoma treated with single-agent
      doxorubicin were reviewed. Nineteen cats met the inclusion criteria for this
      retrospective study. Doxorubicin was given at a dosage of 25 mg/m2 (n = 8) or 1
      mg/kg (n = 11) IV, every 3 weeks for a total of 5 treatments. Four of 16 tested
      cats were positive for feline leukemia virus (FeLV) and all 16 cats tested
      negative for feline immunodeficiency virus. Eight of the 19 cats (42%) responded
      to doxorubicin for a median duration of 64 days (range, 35-575 days). Five cats
      (26%) achieved a complete response (CR) to doxorubicin for a median duration of
      92 days (range, 54-575 days). Partial response was observed in 3 cats.
      Institution was the only significant prognostic indicator for response, with cats
      treated at Colorado State University being more likely to achieve CR than cats
      treated at Tufts University. Cats that achieved CR to doxorubicin and FeLV
      negative cats had significantly longer survival times. Loss of appetite was the
      most common toxicity, observed in 9 cats (47%), and was severe in 5 cats (26%).
      Other toxicoses were less frequent and included vomiting, diarrhea, and
      myelosuppression. Doxorubicin was not very effective at inducing and maintaining
      remission in the cats in this study. Therefore, if doxorubicin is used for the
      treatment of feline lymphoma, it should be combined with other effective
      chemotherapeutic drugs in a combination protocol.

PMID- 11300596
TI  - Plasma vascular endothelial growth factor concentrations in healthy dogs and dogs
      with hemangiosarcoma.
AB  - Vascular endothelial growth factor (VEGF) is a dimeric glycosylated polypeptide
      growth factor with potent angiogenic, mitogenic, and vascular permeability
      enhancing properties specific for endothelial cells. In humans, VEGF seems to
      play a major role in tumor growth, and plasma concentrations correlate with tumor
      burden, response to therapy, and disease progression. This study compared plasma
      VEGF concentrations in healthy client-owned dogs (n = 17) to dogs with
      hemangiosarcoma (HSA; n 16). Dogs with HSA were significantly more likely to have
      detectable concentrations of plasma VEGF (13/17) compared to healthy dogs (1/17;
      P < .001). The median plasma VEGF concentration for dogs with HSA was 17.2 pg/mL
      (range, < 1.0-66.7 pg/mL). Plasma VEGF concentrations in dogs with HSA did not
      correlate with stage of disease or tumor burden, but 1 dog had undetectable VEGF
      during chemotherapy that subsequently increased with disease progression.

PMID- 11300597
TI  - Renal tubular acidosis in horses (1980-1999).
AB  - Renal tubular acidosis (RTA) is characterized by altered renal tubular function
      resulting in hyperchloremic metabolic acidosis. The purpose of the study was to
      describe RTA in 16 horses. No breed or sex predilection was found. The mean age
      at onset of the disease was 7 years of age. The type of diet had no apparent
      effect on development of RTA. The most common clinical signs were depression,
      poor performance, weight loss, and anorexia. Initial blood work revealed a marked
      hyperchloremic metabolic acidosis in all horses and a compensatory respiratory
      response in most horses. Sixty-three percent (10/16) of the horses had some
      evidence of renal damage or disease. Initial treatment consisted of large amounts
      of sodium bicarbonate given intravenously and orally for the prompt correction of
      the acidosis. Response to treatment was largely dependent on the rate of sodium
      bicarbonate administration. Long-term oral supplementation with NaHCO3 was
      required for the maintenance of normal acid-base status in individual horses.
      Recurrence of RTA was noted in 56% (9/16) of the horses. Horses with evidence of
      renal disease had multiple relapses. RTA should be considered as a differential
      diagnosis in horses with vague signs of depression, weight loss, and anorexia.
      The pathogenesis of RTA in horses remains uncertain, but prompt recognition and
      early aggressive intravenous sodium bicarbonate therapy followed by long-term
      oral supplementation seem to be important to successful management.

PMID- 11300598
TI  - Immunophenotypic classification of leukemia in 3 horses.

PMID- 11300599
TI  - Hemolysis associated with patent ductus arteriosus coil embolization in a dog.

PMID- 11300600
TI  - Streptococcal meningoencephalomyelitis in 3 dogs.

PMID- 11300601
TI  - Idiopathic hypereosinophilic syndrome in 3 Rottweilers.
AB  - Three Rottweilers with marked peripheral eosinophilia and infiltration of the
      liver, spleen, lungs, and bone marrow with eosinophils were diagnosed with
      idiopathic hypereosinophilic syndrome (IHES). Mean serum immunoglobulin E
      concentrations were markedly high. On cytogenetic analysis, no evidence of
      karyotypic abnormalities was found in bone marrow aspirates. Despite an extensive
      search, no underlying cause for the eosinophilia could be identified. In this
      study, cytogenetic analysis and measurement of serum IgE concentrations were used
      to differentiate IHES and eosinophilic leukemia.

PMID- 11300602
TI  - Thyroid function tests--what do they really tell us?

PMID- 11300603
TI  - Thyrotropin-releasing hormone stimulation test to assess thyroid function in
      severely sick cats.
AB  - Basal serum thyroxine (T4) concentration and the thyrotropin-releasing hormone
      (TRH) stimulation test were used to assess thyroid function in 36 critically ill
      cats examined between July 1996 and October 1998. Of the 36 cats. hyperthyroidism
      (as underlying or complicating disease) was suspected in 22 based on clinical
      signs, palpable thyroid nodules, and abnormal thyroid gland histology (study
      group). Hyperthyroidism was not suspected in the remaining 14 cats, which served
      as the control group. Based on serum T4 concentrations, suppression of thyroid
      function was documented in 14 (64%) cats of the study group and in 10 (71%) cats
      of the control group. The TRH stimulation test revealed an increase in serum T4
      of less than 50% of the baseline concentration in 18 (82%) cats of the study
      group, and in 6 (43%) cats of the control group. In conclusion, based on the
      results of serum T4 determinations and the TRH stimulation tests, it was not
      possible to differentiate between cats with clinical and histologic evidence of
      thyroid dysfunction (hyperthyroidism) and cats with severe nonthyroidal
      illnesses.

PMID- 11300604
TI  - Evaluation of urinary carnitine and taurine excretion in 5 cystinuric dogs with
      carnitine and taurine deficiency.
AB  - Five client owned dogs with cystinuria were diagnosed with carnitine and taurine
      deficiency while participating in a clinical trial that used dietary management
      of their urolithiasis. Stored 24-hour urine samples collected from the cystinuric
      dogs before enrollment in the clinical diet trial were quantitatively evaluated
      for carnitine and taurine. These results were compared to those obtained from 18
      healthy Beagles. Both groups of dogs were fed the same maintenance diet for a
      minimum of 2 weeks before 24-hour urine collection. The protocol used for 24-hour
      urine collections was the same for cystinuric dogs and healthy Beagles except
      that cystinuric dogs were catheterized at baseline, 8 hours, 12 hours, and at the
      end of the collection, whereas Beagles were catheterized at baseline, 8 hours,
      and at the end of the collection. Three of 5 dogs with cystinuria had increased
      renal excretion of carnitine. None of the cystinuric dogs had increased renal
      excretion of taurine, but cystinuric dogs excreted significantly less (P < .05)
      taurine in their urine than the healthy Beagles. Carnitinuria has not been
      recognized previously in either humans or dogs with cystinuria, and it may be 1
      risk factor for developing carnitine deficiency. Cystinuric dogs in this study
      were not taurinuric; however, cystine is a precursor amino acid for taurine
      synthesis. Therefore, cystinuria may be 1 risk factor for developing taurine
      deficiency in dogs. We suggest that dogs with cystinuria be monitored for
      carnitine and taurine deficiency or supplemented with carnitine and taurine.

PMID- 11300605
TI  - Plasma cholesteryl ester transfer and hepatic lipase activity are related to high
      density lipoprotein cholesterol in association with insulin resistance in type 2
      diabetic and non-diabetic subjects.
AB  - We evaluated the hypothesis that plasma cholesteryl ester transfer (CET) and
      lipase activities are influenced by insulin sensitivity and contribute to the low
      high-density lipoprotein (HDL) cholesterol observed in type 2 diabetic patients
      and insulin-resistant non-diabetic subjects. Sixteen type 2 diabetic and 16 non
      diabetic subjects participated. Diabetic and non-diabetic subjects were divided
      in equal groups of eight subjects with low or high insulin sensitivity, which was
      documented as the glucose infusion rate (M-value) during the last hour of a 3-h
      euglycaemic hyperinsulinaemic clamp (150 mU kg(-1) h(-1), blood glucose target
      4.6 mmol L(-1)). Post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase
      (HL) activities were measured in samples obtained 1-2 weeks before the clamp.
      Plasma CET was measured by a radioisotope method. Compared to non-diabetic men
      with high insulin sensitivity (n = 8) HDL cholesterol was lower in type 2
      diabetic men (n=8, p<0.01) and non-diabetic men (n=8, p <0.05) with low insulin
      sensitivity, and the HDL cholesterylester content was lower in type 2 diabetic
      men with high insulin sensitivity (n=8, p<0.05). In non-diabetic subjects with
      high insulin sensitivity, plasma CET was lower than in the other groups (p<0.05
      for all). Multiple regression analysis showed that plasma CET (p=0.001) and HL
      activity (p=0.02) were independently and negatively associated with the M-value.
      No association between the M-value and LPL activity was observed. Independent
      negative relationships of HDL cholesterol with plasma CET (p = 0.04) and HL
      activity (p=0.03) were observed. This study supports the hypothesis that a low
      HDL cholesterol associated with insulin resistance in type 2 diabetic and non
      diabetic subjects is related to a high plasma CET and a high HL activity.

PMID- 11300606
TI  - Scavenger treatment of free radical injury in familial amyloidotic
      polyneuropathy: a study on Swedish transplanted and non-transplanted patients.
AB  - Since oxidative stress has been implicated in amyloid diseases, a study of
      scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23
      familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a
      liver transplantation for the disease. Twenty patients completed the 6-month
      study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin
      E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They
      were evaluated clinically and by immunohistochemical measurement of
      hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For
      non-transplanted patients, no improvement was found for HNE in relation to the
      amyloid content in biopsy specimens, whereas a tendency to a decreased amount was
      noted for transplanted patients. Clinically, no differences were found for non
      transplanted patients, but an increased nutritional status, measured by a
      modified body mass index (mBMI) was noted for transplanted patients. In summary,
      scavenger treatment with the drugs and doses used in the present study appears to
      be unable to decrease lipid peroxidation in amyloid-rich tissue in non
      transplanted FAP patients. For transplanted patients, lipid peroxidation tended
      to decrease, and the nutritional status measured by mBMI improved, even though
      the findings may be explained by liver transplantation alone, scavenger treatment
      may facilitate recovery after transplantation.

PMID- 11300607
TI  - Evaluation of features of syndrome X in offspring of Caribbean patients with Type
      2 diabetes.
AB  - OBJECTIVE: To determine whether the features of metabolic syndrome X are more
      common in offspring of patients with Type 2 diabetes than in control subjects
      without immediate family history of diabetes. MATERIALS AND METHODS: Thirty-four
      young offspring of patients with Type 2 diabetes and 27 healthy control subjects
      underwent a standard oral glucose tolerance tests (OGTT; 75 g glucose in 300 ml
      water). Anthropometric indices, blood pressure, plasma glucose, serum lipids and
      insulin levels were measured. Homeostasis model assessment (HOMA) was used to
      assess basal insulin resistance (IR) and sensitivity (%S). RESULTS: The offspring
      had significantly higher mean+/-SD BMI (p<0.01) and basal serum triglyceride
      (p<0.05), insulin (p<0.05), insulin/glucose ratio (p<0.01), and lower %S
      (p<0.001) than the control subjects, in spite of similar fasting plasma glucose
      concentrations. Multiple linear regression analysis showed that these differences
      were independent of BMI. Although, the two groups of subjects had similar serum
      HDL-Cholesterol, LDL-cholesterol and blood pressure levels, %S was significantly
      related to diastolic BP (p<0.01) and serum triglyceride levels (p<0.01).
      CONCLUSIONS: In comparison with the healthy control subjects, the insulin
      resistant offspring have higher levels of the identified syndrome X features
      independent of obesity. These features were quantitatively lower than the values
      reported in offspring of white Caucasian and African-American patients.

PMID- 11300608
TI  - Correlations between biochemical markers of bone resorption and creatinine
      excretion.
AB  - There were two reasons for doing this study. The first was to assess whether
      expressing biochemical markers of bone resorption as a ratio to creatinine
      excretion influences the correlations between them. The second was to assess
      whether biochemical markers of bone resorption are correlated with creatinine
      excretion, which is a biomarker of muscle mass. Three biochemical markers of bone
      resorption, free deoxypyridinoline (DPD), N-telopeptides (NTx) and C-telopeptides
      (CTx), together with creatinine (cr), were measured in 24-h urine samples of 45
      healthy people (26 women and 19 men). The urinary concentrations of DPD, NTx and
      CTx were highly correlated with each other. These relationships were weakened, or
      no longer statistically significant, when the markers were expressed as a ratio
      to cr excretion. The 24-h excretion of each of the markers was correlated with 24
      h cr excretion in men, but only 24-h DPD was correlated with 24-h cr excretion in
      the women. The men had significantly higher 24-h excretion rates of each of the
      markers than the women did. Since muscle mass is related to skeletal mass, these
      data suggest that in healthy people the rate of bone resorption may be a function
      of skeletal size as well as the rate of bone turnover. For small human studies 24
      h urine sampling is recommended in preference to untimed sampling. However, for
      clinical purposes, or for large clinical trials, this may not be practical.

PMID- 11300609
TI  - Radioimmunoassay for N-terminal probrain natriuretic peptide in human plasma.
AB  - Measurement of plasma levels of natriuretic peptides has been used to assess left
      ventricular dysfunction and prognosis. Recently levels of the N-terminal peptide
      fragment of the precursor of brain natriuretic peptide have been reported to be
      present in peripheral plasma and to be increased in chronic heart failure
      patients. Our aim in this study was to develop a radioimmunoassay for N-terminal
      proBNP, to compare its plasma concentrations in control subjects and in patients
      with end-stage heart failure and to define its relation to brain natriuretic
      peptide (BNP). A polyclonal antibody was raised in rabbits against human N
      terminal proBNP fragment (amino acid 1-21). The plasma N-terminal proBNP
      concentrations were assayed directly without extraction. No detectable cross
      reactivity existed with other natriuretic peptides: BNP, ANP or N-terminal
      proANP. The assay had a detection limit (2 SD from zero) of 9.7 pmol/L. Plasma N
      terminal proBNP was 29 (13-75) (median (range)) pmol/L in the control group.
      There were no gender difference, male: 28 (13-61) vs. female 33 (13-75) pmol/L,
      p= NS, but there was a positive correlation to age (r=0.52, p<0.0001). In
      patients with end-stage heart failure the median N-terminal proBNP levels were
      increased significantly 616 (114-2781) pmol/L (p<0.001) and in pooled data N
      terminal proBNP showed a close correlation to BNP (r=0.96, p<0.0001). Size
      exclusion of plasma extracts indicated that proBNP (1-108) may circulate both as
      intact prohormone and as split products, N-terminal proBNP (1-76) and BNP (77
      108). Our results support the concept that N-terminal proBNP measurement could be
      a valuable tool in the biochemical indication of increased cardiac wall stress.

PMID- 11300610
TI  - The impact of glycaemic control on autoregulation of glomerular filtration rate
      in patients with non-insulin dependent diabetes.
AB  - The ability of the kidney to maintain constancy of glomerular filtration rate
      (GFR) over a wide range of renal perfusion pressures is termed autoregulation.
      Defective autoregulation of GFR has been demonstrated in patients with diabetic
      and non-diabetic nephropathy and in streptozotocin diabetic rats during
      hyperglycaemia. Information on the potential impact of acute changes in glycaemic
      control on autoregulation of GFR in diabetic patients is lacking. Therefore the
      aim of our study was to evaluate the effect of acute lowering of blood pressure
      (BP) on GFR during normoglycaemia and hyperglycaemia. We investigated 14 (12m/2f)
      normoalbuminuric patients with non-insulin dependent diabetes (NIDDM). The
      patients were examined in random order on two separate days with blood glucose
      (BG)<10 mmol/L or with BG>15 mmol/L. GFR (single shot [51Cr] EDTA plasma
      clearance technique) was measured twice each day; first without clonidine
      (baseline) followed by intravenous injection of clonidine 100-150 microg. We
      measured BG (One Touch 2), and BP (Takeda TM2420) several times during each GFR
      measurement. Clonidine reduced mean arterial blood pressure with 20 (1.4) vs. 16
      (1.2) mmHg (mean (SE)) with BG<10mmol/L and with BG>15 mmol/L, respectively
      (p=0.053). GFR diminished in average from 92 (3.1) to 86 (3.7) ml/min/1.73m2 with
      BG<10 mmol/L (p<0.05), and from 102 (4.1) to 98 (4.2) ml/min/1.73 m2 with BG> 15
      mmol/L, NS. Mean difference between changes in GFR (95% confidence interval)
      between the examination with BG<10 mmol/L and with BG>15 mmol/L were 2.3 (-1.3 to
      5.9) ml/min/1.73 m2 (NS). The mean BG during normoglycaemia was 6.9 (0.3) vs.16.9
      (0.4) during hyperglycaemia. CONCLUSION: Our study suggests that acute changes in
      glycaemic control have no detectable effect on autoregulation of GFR in NIDDM
      patients. Hyperglycaemia enhances GFR.

PMID- 11300611
TI  - Analysis of preformed xenoreactive antibodies in the discordant guinea pig to rat
      model using a guinea pig fibroblast-like cell line.
AB  - In the discordant guinea pig (gp) to rat model of xenotransplantation,
      circulating xenoreactive natural antibodies (XNA) recognizing gp antigens are
      usually determined by an ELISA using membrane extracts of gp platelets. We
      analysed the lung-derived, fibroblast-like cell line JH 4 to detect XNA by ELISA
      or immunoblot, which was compared to primary gp cells, i.e. platelets, liver- and
      spleen cells. All membrane extracts proved to be useful to detect rat XNA
      directed against gp antigens by ELISA. In general, IgM responses of Lewis or C6
      deficient PVG rats (PVG/C6-) were higher as compared to IgG responses. However,
      we observed great inter-individual variabilities. The strongest IgM response of
      Lewis rat sera was observed when the JH 4 cell line or gp liver cells were used
      as antigen. JH 4 cells also showed the strongest xenoreactivity with sera from
      PVG/C6- rats. These data demonstrate that JH 4 cells prove useful as antigen
      source for XNA ELISA. In immunoblot, individual sera of the two different rat
      strains showed the same antigen patterns using a gp membrane extract of one
      particular cell type. However, the different gp cell types showed a distinct
      pattern of antigen expression. Whereas the JH 4 cells, platelets and spleen cells
      express xenoreactive proteins of the same size, a unique pattern of proteins was
      detected in liver cells.

PMID- 11300612
TI  - Turnover of 125I-labelled tissue kallikrein following intraduodenal or
      intravenous administration.
AB  - Tissue kallikrein is released in the body both physiologically and in many
      inflammatory disorders. Little is, however, known about the turnover of released
      tissue kallikrein in humans. Approximately 1 mg of tissue kallikrein (mol wt
      43,000 Da) was purified from 85 L human urine by: (1) ultracentrifugation, (2)
      filtration through an aprotinin-coupled Sepharose 4B column, followed by (3) gel
      filtration over a Sephadex G-75 column. The elimination, after intraduodenal or
      intravenous administration of purified tissue kallikrein radiolabelled with 125I,
      was followed by collecting serial samples of plasma, urine and faeces from three
      volunteers. Within 72 h, about 96% of the intraduodenally administered
      radioactivity had been excreted in urine, and approximately 5.4% in faeces,
      mainly as 125I. No intact 125I-tissue kallikrein was found in plasma, urine or
      faeces after the intraduodenal instillation of the protein. The plasma half-life
      of 125I-tissue kallikrein up to 3 h after intravenous injection was 9 min and,
      thereafter, 20 h. The 125I-tissue kallikrein was quickly bound to a plasma
      protein with a mol wt of about 67 kDa, but some of the radioiodinated tissue
      kallikrein was still unbound 15 min after injection, judged by gel filtration on
      Sephadex G-200 columns. Most of the radioactivity was excreted in the urine as
      125I, but about 4-6% was recovered as free 125I-tissue kallikrein. CONCLUSION:
      The use of tissue kallikrein as an oral drug appears, therefore, to be useless.
      Tissue kallikrein released into plasma seems to be quickly bound to a protein
      with a mol wt of 67 kDa, probably kallistatin or Protein C inhibitor, but some
      tissue kallikrein seems to be unbound and may have some physiological or
      pathophysiological action. The unbound tissue kallikrein is, at least partly,
      cleared from the circulation by the kidneys, and tissue kallikrein in the urine
      may partly be derived from plasma.

PMID- 11300613
TI  - Role of phospholipid transfer protein and prebeta-high density lipoproteins in
      maintaining cholesterol efflux from Fu5AH cells to plasma from insulin-resistant
      subjects.
AB  - Plasma phospholipid transfer protein (PLTP) enhances the generation of prebeta
      high density lipoproteins (HDL) that may act as initial acceptors of cellular
      cholesterol, and are likely to play an important role in the antiatherogenic
      process of reverse cholesterol transport. We examined the interrelationships
      between insulin resistance, the ability of plasma to stimulate cellular
      cholesterol efflux, HDL cholesterol, plasma PLTP activity and prebeta-HDL in 12
      non-diabetic, non-smoking, normotriglyceridaemic men. Cholesterol efflux from
      Fu5AH cells to plasma, plasma lipoproteins, PLTP activity and prebeta-HDL
      formation as measured in incubated plasma were determined after a 12-h fast.
      Insulin sensitivity was assessed by a euglycaemic, hyperinsulinaemic clamp (M
      value). HDL cholesterol was positively correlated with the M-value (r=0.65, p<
      0.05), whereas plasma PLTP activity (r= -0.59, p <0.05) and prebeta-HDL in
      incubated plasma (r= -0.66, p<0.05) were negatively correlated with the M-value.
      Thus, the lower the insulin sensitivity, the lower was HDL cholesterol and the
      higher were plasma PLTP activity and prebeta-HDL. Cellular cholesterol efflux
      tended to be correlated with HDL cholesterol (r=0.55, p < 0.10) as well as with
      plasma PLTP activity (r=0.56, p<0.10) and was positively correlated with prebeta
      HDL in incubated plasma (r=0.74, p<0.01). No positive correlation between the M
      value and cellular cholesterol efflux was found (r= -0.34, ns). These preliminary
      results support the hypothesis that, despite a lower HDL cholesterol, the ability
      of plasma from insulin-resistant subjects to promote cellular cholesterol efflux
      is not impaired, as a consequence of a higher plasma PLTP activity and enhanced
      prebeta-HDL formation.

PMID- 11300614
TI  - A standardized method of oleic acid infusion in experimental acute respiratory
      failure.
AB  - Commonly, acute respiratory failure (ARF) in laboratory animals is induced
      through the intravenous infusion of oleic acid (OA). The methods by which OA is
      infused, and the methods by which droplets are generated, differ greatly among
      investigators. The resulting ARF, and the distribution of the underlying
      pulmonary pathology, are not highly reproducible. A method was developed that
      generated a reproducible, known spectrum of OA microdroplets. This method was
      applied to infuse a known volume of OA into the vena cava superior (VCS) in
      sheep, to induce ARF. In vitro studies were conducted in an observation chamber
      filled with saline or plasma. The distal end was cut off a 7F Swan Ganz catheter.
      The catheter was immersed in an observation chamber. Through one of the channels
      OA was infused at a low flow rate while saline was infused at variable high flow
      rates through a second channel. The size and the distribution spectrum of the so
      generated OA droplets were determined from flash photographic studies. The
      distribution and the size of the microdroplets depended on the media in the
      observation chamber, and on the saline infusion rate. In vivo studies were
      conducted in six anesthetized and ventilated sheep. We chose in our in vivo
      studies a saline flow rate of 126 mL/min and at an OA flow rate of 3 mL/min, that
      generated OA microdroplets 125 +/- 32 microm SD in size. OA microdroplets were
      generated in situ in the VCS and where then embolized into small pulmonary
      vessels. A total dose of 0.06 mL/kg of OA was administered in three separate
      doses of 0.02 mL/kg, each 10 min apart. The evolving ARF was manifested by a
      progressive deterioration in arterial blood gases, and a uniform opacification of
      all lung fields on chest X-ray films. At autopsy the lungs were diffusely
      consolidated. CONCLUSION: A method was developed to standardize the infusion of
      OA in laboratory animals that resulted in diffuse involvement of the all lungs,
      with a predictable and reproducible severe acute respiratory failure.

PMID- 11300615
TI  - Measured fraction of carboxyhaemoglobin depends on oxygen saturation of
      haemoglobin.
AB  - The use of the OSM3 oximeter for measurement of the fraction of
      carboxyhaemoglobin (FCOHb) in blood allows for estimation of total circulating
      haemoglobin mass (Hb(tot)) by using the carbon monoxide rebreathing method. To
      ensure high accuracy of Hb(tot) estimation, potential sources of analytical
      errors should be identified and adjusted for. Based on observed differences in
      results of measured FCOHb between simultaneously sampled, arterialized and venous
      blood samples we investigated the influence of haemoglobin oxygen saturation
      (sO2) on results of measured FCOHb. Blood from nine healthy non-smokers was
      tonometered with gas mixtures containing 94% N2 or air and 6% CO2. The resulting
      oxygenated and deoxygenated specimens were mixed in different proportions to
      obtain varying sO2 values in the same blood. sO2, fractions of dyshaemoglobins,
      pO2, pCO2 and pH were measured at each step. FCOHb was significantly (p<0.001)
      higher in oxygenated (median, range: 0.6%, 0.4-0.9%) compared to deoxygenated (
      0.2%, -0.5-0.0%) blood. Regression analysis identified the sO2 as the most
      important factor explaining 86% of the variance in observed changes in FCOHb. The
      observed sO2 effect has important implications on calibration procedure of OSM3,
      accuracy of measured FCOHb, and FCOHb dependent calculations such as estimation
      of Hb(tot) and related quantities. If the highest accuracy of FCOHb measurement
      is needed, an sO2 effect on results of measured FCOHb has to be considered and
      adjusted for.

PMID- 11300616
TI  - Magnesium regulation of Ca2+ channels in smooth muscle and endothelial cells of
      human allantochorial placental vessels.
AB  - In human allantochorial placental vessels, the vascular tone is regulated by
      membrane potential controlled by the ion flux through K+ and Ca2+ channels. The
      effects of MgCl2 and MgSO4 were studied on the membrane potential of vascular
      smooth muscle cells (VSMCs) and of endothelial cells (VECs). The membrane
      potential was the main factor of the excitation-contraction coupling of placental
      vessels. The VSMCs and VECs were predepolarized by high external K+, which
      blocked voltage-sensitive K+ channels, and depolarized by serotonin addition
      which activated Ca2+ influx through voltage-gated Ca2+ channels. Addition of
      MgCl2 or MgSO4 in the external medium induced a depolarization level lower than
      the previous level, as nifedipine a Ca2+ blocker, corresponding to a Ca2+ influx
      reduction in VSMCs and VECs and inducing relaxation of the cells. The effect of
      MgCl2 and MgSO4 was the same on VSMCs and VECs, but the depolarization level
      reduction was more important with MgCl2 than MgSO4 on VSMCs. These data suggested
      that Mg salts regulated the Ca2+ influx through voltage-gated Ca2+ channels in
      VSMCs and VECs and consequently the tonus of human allantochorial placental
      vessels and that there was a difference between Mg salts.

PMID- 11300617
TI  - In vivo and in vitro effects of magnesium deficiency on hepatic haptoglobin mRNA
      levels.
AB  - We previously showed that haptoglobin (Hp) was increased in the plasma of dietary
      magnesium (Mg)-deficient rats. The present study was performed to examine the
      effects of dietary Mg-deficiency and Mg2+ deficit in culture medium on Hp mRNA
      levels in liver and isolated hepatocytes, respectively. The Hp mRNA level in the
      liver increased significantly from day 10 to day 30 in rats on a Mg-deficient
      diet (Mg; 0.001 per cent). In the cultured hepatocytes, lowering the Mg2+ level
      in the culture medium from 0.92 mM to 0.46 mM did not affect the Hp mRNA level of
      hepatocytes. When IL-1beta or IL-6 was added to the culture medium, the Hp mRNA
      level increased much more in the hepatocytes cultured in low Mg2+ medium (Mg2+;
      0.46 mM) than in those cultured in the control Mg2+ medium (Mg2+; 0.92 mM). These
      results suggest that the increase in plasma Hp level during dietary Mg deficiency
      depends on the increase in Hp mRNA level in the liver, and that this increase in
      mRNA is not only directly correlated with a low Mg level in plasma, but also
      indirectly correlated with cytokines.

PMID- 11300618
TI  - Magnesium and some psychological features in two groups of pupils (magnesium and
      psychic features).
AB  - The aim of our study was to compare Mg levels and psychological features in two
      pupils groups with different conditions. It also ascertained the relationship
      between Mg levels and some aspects of intellectual development (attention, memory
      and intelligence) and personality features (psychoticism, neuroticism and
      extraversion). 103 pupils from an orphanage and 100 pupils from a secondary
      school were investigated. Serum and erythrocyte magnesium levels were determined
      and psychological examinations were accomplished with specific tests. The study
      indicated a difference between the two groups as regards magnesium level and the
      investigated psychological features. A direct correlation between magnesium level
      and neuroticism was demonstrated.

PMID- 11300619
TI  - Effect of external magnesium on intracellular free sodium: Na+ flux via Na+/Mg2+
      antiport is masked by other Na+ transport systems in rat cardiac myocytes.
AB  - Mg2+ efflux from heart cells on a Na+/Mg2+ antiport has been postulated, but the
      Na+ flux component of the antiport has not been demonstrated. The study aimed to
      establish if the Na+ flux component could be measured by following changes in
      [Na+]i with SBFI during conditions known to reverse the antiport (5 mmol/L
      Mg2+(o), Na+(o)- & Ca2+(o)-free): and after minimising the activity of other Na+
      transport pathways. Resting [Na+]i was 8 +/- 0.7 mmol/L (mean +/- S.E., n = 39
      cells) in normal Tyrode's solution. [Na+]i decreased below the normal level in
      all cells (a decline of 4-5 mmol/L, n = 21) during perfusion with 5 mmol/L
      Mg2+(o) (Na+(o)- & Ca2+(o)-free). Controls using 1 mmol/L Mg2+(o) showed similar
      declines in [Na+]i, but the fall was greatest when Na+(o) was replaced by K+(o)
      (decline of 6 mmol/L) rather than the tetramethylammonium ion (TMA+). The rate of
      decrease in [Na+]i during perfusion with 5 mmol/L Mg2+(o) (Na+(o)- & Ca2+(o)
      free) was slowed by 20 microM ouabain (n = 5) or by elevation of pHo to pH 9 (n =
      7) so that [Na+]i remained close to the initial value. The decrease of [Na+]i was
      not affected by 10 microM imipramine (n = 15). These data suggest that the Na+
      efflux component of the Na+/Mg2+ antiport is masked in Na+(o)- and Ca2+(o)-free
      conditions by other Na+(i) efflux pathways.

PMID- 11300620
TI  - The influence of magnesium supplementation on magnesium and calcium
      concentrations in hair of children with magnesium shortage.
AB  - 46 children, aged 2-6 years, with decreased magnesium concentrations in hair,
      were studied. Magnesium supplementation consisted of Asmag preparation for 3
      months and multivitamin Multi-tabs preparation (containing magnesium, but without
      calcium) for the following 4 months. Control studies were performed again after 7
      months of treatment, i.e. 12 months after the initial measurements (the same
      season of the year--early spring). The results proved increases of both magnesium
      (from 7.74 microg/g dry mass to 11.03 microg/g dry mass) and calcium (from 159.82
      mg/g dry mass to 191.60 mg/g dry mass) concentrations in hair. Increased
      magnesium concentrations were observed in 40 studied children (86.95 per cent).
      Post supplementation magnesium deficiency was found in 22 children (47.83 per
      cent), and four children (8.70 per cent) showed further worsening of
      hypomagnesemia. Increased calcium concentrations were found in 42 children (91.30
      per cent), while decreased Ca levels were found in 4 children (8.70 percent). The
      achieved results indicate a positive influence of that form of compensation of
      magnesium deficiency, and suggest the need of individual selection of doses and
      period of Mg supplementation. The initial level of hypomagnesemia, presence of
      factors that might inhibit intestinal absorption, accompanying diseases that
      might cause decrease in magnesium concentration and other factors that might
      influence the total body magnesium concentration should be taken into account
      while designing the supplementation therapy.

PMID- 11300621
TI  - Magnesium deficiency promotes muscle weakness, contributing to the risk of sudden
      infant death (SIDS) in infants sleeping prone.
AB  - A review was published (1991) of 19 retrospective case-control studies that had
      investigated the relationship between prone sleeping position (on the stomach)
      and the sudden infant death syndrome (SIDS). These studies, which had been
      conducted between 1965 and 1990 in New Zealand, Australia, England, France and
      the Netherlands, showed an overall higher rate of SIDS in infants who usually
      slept prone. In those countries, vigorous community intervention to change
      babies' sleep position away from the prone has resulted in marked declines of 50
      per cent or more in the rate of SIDS. Such encouraging reports from many
      countries prompted the American Academy of Pediatrics to recommend that infants
      be placed to sleep on their backs to reduce the risk of SIDS. This was followed
      by a successful campaign in the United States between mid-1994 and 1998. Despite
      the decreased incidence, SIDS remains the leading cause of death in infants 1
      month to 1 year of age of industrialized nations of the world. Studies have been
      conducted in human infants, mechanical models and animal models to learn the role
      of risk factors in prone sleeping infants. Soft bedding, thermal stress and
      biologic risk factors such as impaired ventilatory and arousal responsiveness are
      among many factors that have been investigated. Hunt states that there is not a
      single unifying factor that explains increased SIDS in prone sleeping infants.
      Two major studies conducted in the 1970s showed: (1) muscle weakness in the upper
      half of the body in infants who subsequently died of SIDS, and (2) shoulder
      hypotonia in near-miss for SIDS infants. An infant sleeping face-down in the
      prone position could be jeopardized if he lacked the muscle strength to shift his
      position or turn his head to rescue himself from a life-threatening situation. In
      contrast, recent studies in neonates sleeping in the prone position report that
      normal infants can spontaneously arouse and turn their heads. Some data support
      the hypothesis that magnesium deficiency contributes to SIDS. Muscle strength is
      seriously impaired in the young magnesium deficient subject, while magnesium
      rapidly reverses muscle weakness. In rats, marginal deprivation in dietary
      magnesium reduces exercise capacity, an early effect of magnesium deficiency
      which is preventable by consuming magnesium-enriched mineral water. It is
      concluded that magnesium deficiency is at least one major unifying factor that
      explains increased SIDS in prone sleeping infants.

PMID- 11300622
TI  - The behavioral and anatomical effects of MgCl2 therapy in an electrolytic lesion
      model of cortical injury in the rat.
AB  - Magnesium has been shown to be involved with the processes associated with brain
      injury and its use in animal models of brain injury has received considerable
      attention. The present paper reviews the use of MgCl2 therapy to facilitate
      behavioral recovery and to reduce subcortical degeneration in an electrolytic
      lesion model of cortical injury in the rat. Several studies were performed which
      compared the effectiveness of MgCl2 to other established neuroprotective agents,
      examined the preoperative administration of MgCl2, and examined the effectiveness
      of MgCl2 in a lesion model that produces chronic behavioral impairments. The
      results from these studies indicate that MgCl2 therapy is effective in
      facilitating recovery of function and limiting subcortical degeneration, is as
      effective as other neuroprotective agents, and can induce recovery of function in
      a chronic lesion model. These results suggest that MgCl2 therapy is effective in
      facilitating recovery of function in an electrolytic lesion model of cortical
      injury.

PMID- 11300623
TI  - A possible advance in arterial gene therapy for aortic complications in the
      Marfan syndrome by local transfer of an antisense Mg-dependent hammerhead
      ribozyme.
AB  - Aortic dissection and rupture make the Marfan Syndrome (MFS), one of the most
      highly lethal genetic condition, but these events are preceded by simple aortic
      root dilatation over a long period. A hydrogel coated angioplasty balloon might
      constitute a possible aortic vector to locally deliver an antisense Mg-dependent
      hammerhead ribozyme capable to control specifically the genetic alteration of
      fibrillin 1 responsible for the connective tissue disorder of MFS.

PMID- 11300624
TI  - New insights from cDNA array techniques in magnesium biology research.

PMID- 11300625
TI  - Experimental design of an optimal phase duration control strategy used in batch
      biological wastewater treatment.
AB  - The paper presents the design of an algorithm used in control of a sequencing
      batch reactor (SBR) for wastewater treatment. The algorithm is used for the on
      line optimization of the batch phases duration which should be applied due to the
      variable input wastewater. Compared to an operation with fixed times of batch
      phases, this kind of a control strategy improves the treatment quality and
      reduces energy consumption. The designed control algorithm is based on following
      the course of some simple indirect process variables (i.e. redox potential,
      dissolved oxygen concentration and pH), and automatic recognition of the
      characteristic patterns in their time profile. The algorithm acts on filtered on
      line signals and is based on heuristic rules. The control strategy was developed
      and tested on a laboratory pilot plant. To facilitate the experimentation, the
      pilot plant was superimposed by a computer-supported experimental environment
      that enabled: (i) easy access to all data (on-line signals, laboratory
      measurements, batch parameters) needed for the design of the algorithm, (ii) the
      immediate application of the algorithm designed off-line in the Matlab package
      also in real-time control. When testing on the pilot plant, the control strategy
      demonstrated good agreement between the proposed completion times and actual
      terminations of the desired biodegradation processes.

PMID- 11300626
TI  - Update: assessment of risk for meningococcal disease associated with the Hajj
      2001.
AB  - During late March and early April 2000, four cases of meningococcal disease
      caused by Neisseria meningitidis serogroup W-135 were identified among U.S.
      pilgrims returning from the Hajj in Saudi Arabia, their close contacts, and
      communities. These cases occurred as part of a larger epidemic in which
      approximately 400 cases caused by a similar and unusual strain were identified
      worldwide. The Hajj, an annual pilgrimage to the major holy places of Islam, is
      attended by approximately two million persons from approximately 140 countries,
      including an estimated 15,000 from the United States.

PMID- 11300627
TI  - Apparent global interruption of wild poliovirus type 2 transmission.
AB  - In 1988, the World Health Assembly of the World Health Organization (WHO)
      resolved to eradicate poliomyelitis by 2000. Since then, the WHO Region of the
      Americas and Western Pacific Region have been certified free of polio, and the
      European Region is approaching 3 years since the last confirmed case of polio.
      Transmission of wild poliovirus types 1 and 3 continues to decline in the other
      WHO regions. This report summarizes the evidence, obtained through surveillance
      for acute flaccid paralysis (AFP), supporting the global interruption of wild
      poliovirus type 2 transmission.

PMID- 11300628
TI  - Severe malnutrition among young children--Georgia, January 1997-June 1999.
AB  - In October 1999, the Georgia Department of Human Resources (GDHR) was notified of
      two cases of severe malnutrition in toddlers. Both cases were associated with the
      use of commercial alternative milk. In response, GDHR and CDC reviewed Georgia
      hospital records to assess the frequency and cause of hospitalized cases of
      rickets and protein energy malnutrition (PEM). The findings of this review
      indicated that, although no new cases were associated with milk alternatives,
      three children had PEM and six had vitamin D deficiency rickets. The children
      with rickets had been breast fed for approximately 6 months while receiving no
      vitamin D supplementation. Rickets is preventable through the adequate intake of
      vitamin D. The American Academy of Pediatrics (AAP) is examining vitamin D
      supplementation among breast-fed infants.

PMID- 11300629
TI  - Outbreak of community-acquired pneumonia caused by Mycoplasma pneumoniae-
      Colorado, 2000.
AB  - On May 18, 2000, the Colorado Department of Public Health and Environment (CDPHE)
      was contacted by a family physician in Moffat County, Colorado (1998 population:
      12,700), about a large number (>50) of community-acquired pneumonia cases
      diagnosed by chest radiograph in a group practice over several months. An
      investigation by state public health officials and CDC implicated Mycoplasma
      pneumoniae as the cause of illness. This report summarizes the results of the
      investigation and underscores the importance of investigating outbreaks of severe
      unexplained respiratory illness to enable implementation of appropriate treatment
      and control measures.

PMID- 11300630
TI  - Diode laser cyclophotocoagulation in refractory glaucoma: comparison between
      pediatric and adult glaucomas.
AB  - OBJECTIVE: To evaluate the outcome of contact transscleral diode laser
      cyclophotocoagulation (CTDC) in eyes with advanced glaucoma and to compare the
      efficacy in pediatric and adult patients. PATIENTS AND METHODS: Included in the
      study were 41 eyes (39 patients) with advanced glaucoma (15 eyes of 13 pediatric
      patients and 26 eyes of 26 adult patients). The patients were followed at least
      for six months or until failure of the procedure, if shorter than 6 months. The
      mean follow-up of all patients was 10 months (median 8 months, range 3-24
      months); the mean pretreatment intraocular pressure (IOP) was 34.5+/-10.9 mm Hg
      for all cases, 36.2+/-12.6 mm Hg in adult cases and 31.6+/-6.5 mm Hg in pediatric
      cases. RESULTS: At last follow-up after first treatment, there was significant
      decrease in IOP and the mean reduction in IOP was 12.11+/-10.5 mm Hg for all
      eyes. The mean reduction in IOP adult (13.6+/-11.8 mm Hg) and (9.9+/-6.8 mm Hg)
      patients. While the success rate after the first diode laser therapy was 59%, it
      increased to 75% after retreatments. The most common complications were
      conjunctival hyperemia and anterior chamber reaction. There was no difference in
      the complication rate between the pediatric and adult cases. CONCLUSION: CTDC is
      a safe and effective therapy in eyes with advanced refractory glaucoma in the
      short term. But multiple applications may be needed in the long term. The results
      in adult and pediatric patients were found to be similar in efficacy and safety.

PMID- 11300631
TI  - The outcome of the functioning filter after subsequent cataract extraction.
AB  - OBJECTIVE: To evaluate and compare the outcome of functioning filtration surgery
      followed by cataract surgery with posterior intraocular lens implantation by both
      phacoemulsification and extracapsular cataract extraction (ECCE) techniques in
      glaucomatous eyes. PATIENTS AND METHODS: We retrospectively evaluated the
      clinical course of 77 eyes (68 patients) that after successful trabeculectomy,
      underwent cataract surgery by either phacoemulsification or ECCE techniques. We
      determined the frequency of partial and absolute failure following cataract
      surgery by either phacoemulsification or ECCE in eyes with functioning
      trabeculectomies. Partial failure of intraocular pressure (IOP), control after
      cataract extraction was defined as the need for an increased number of
      antiglaucoma medications or argon laser trabeculoplasty to maintain IOP < or
      =21mm Hg. Complete failure of IOP control after cataract surgery was defined as
      an IOP >21 mm Hg on at least two consecutive measurements one or more weeks apart
      or the performance of additional filtration surgery. Failure rates were
      calculated using the Kaplan-Meier actuarial method. Failure rates between
      phacoemulsification and ECCE subgroups were compared using the log rank test.
      RESULTS: The probability of partial failure by the third postoperative year after
      cataract surgery was 39.5% in the phacoemulsification subgroup and 37.3% in the
      ECCE subgroup. This small difference is not statistically significant (P = 0.48).
      The probability of complete failure by the fourth postoperative year after
      cataract surgery was 12.0% in the phacoemulsification subgroup and 12.5% in the
      ECCE subgroup. This difference is also not statistically significant (P = 0.77).
      At the 6-month follow-up visit, visual acuity of both groups improved one or more
      lines in 87.0% of patients, and worsened one or more lines in 3.9% of patients.
      Sixty-one percent achieved visual acuity of 20/40 or better. The most frequent
      complication was posterior capsular opacification requiring laser capsulotomy
      that occurred in 31.2% of patients. CONCLUSION: Cataract extraction by either
      phacoemulsification or ECCE following trabeculectomy surgery may be associated
      with a partial loss of the previously functioning filter and the need for more
      antiglaucoma medications to control IOP.

PMID- 11300632
TI  - Long-term results of various anterior capsulotomies and radial tears on
      intraocular lens centration.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the long-term effects of various anterior
      capsulotomies and radial tears on intraocular lens (IOL) centration. MATERIALS
      AND METHODS: Ninety-five eyes of 87 senile cataract patients operated with
      extracapsular technique were evaluated in IOL tilt and decentration with a new
      method of measurement. According to the type of anterior capsulotomy and number
      of radial tears, five groups were constituted as, can opener, envelope, continous
      curvilinear capsulorrhexis (CCC), CCC with one radial tear (relaxing incision at
      quadrant 12), and CCC with two relaxing incisions (relaxing incisions at
      quadrants 6 and 12), respectively. RESULTS: Early decentration and tilt in groups
      CCC and CCC with one radial tear were significantly lower than the other groups
      (P < 0.05). Late decentration and tilt in the CCC group were significantly lower
      than the other groups (P < 0.01). Highest values of tilt and decentration were
      determined in envelope capsulotomy. Additional symmetric relaxing incision at
      quadrant 6 revealed no effect on the prevention of decentration and tilt compared
      to one relaxing incision. CONCLUSION: CCC with one radial tear is not ideal but
      sufficient for IOL centration. All other anterior capsulotomy techniques, other
      than intact CCC, do not guarantee the IOL centration.

PMID- 11300633
TI  - Hollow bandage contact lens.
AB  - OBJECTIVE: To report on the use of a new bandage contact lens (BCL) for a leaking
      filtering bleb. PATIENTS AND METHODS: A hollow BCL, with an internal central
      opening of 6 mm, has been applied on three eyes that had leaking blebs shortly
      after either trabeculectomy or combined cataract extraction and trabeculectomy,
      each with a fornix-based conjunctival flap. RESULTS: The treatment with this lens
      was found beneficial: the leakage subsided and the patients were comfortable with
      the lens. The internal hollow of the BCL enabled us to monitor the intraocular
      pressure throughout the entire follow-up period without transient and repeated
      removal of the BCL. CONCLUSION: The new hollow BCL was found efficacious. The
      study suggests that this lens may have advantages over the commonly used BCLs
      that are related to the elimination of the need for its frequent removal and
      reinsertion for tonometry. This decreases the risk of both the exposure of the
      lens and the filtering bleb to contamination and the interference with the
      continuity of the process of conjunctival epithelial closure.

PMID- 11300634
TI  - Use of Erbium:YAG laser in the treatment of palpebral xanthelasmas.
AB  - OBJECTIVE: In light of the research and the use of lasers in the therapy of
      xanthelasmas, the authors report their experience in the treatment of this
      pathology with Erbium:YAG laser. MATERIALS AND METHODS: In 30 patients, all
      female, 70 xanthelasmas were treated with Erbium:YAG laser, 65 (93%) of which
      were on the upper eyelid and 5 (7%) on the lower eyelid, varying from 1 x 1.5 mm
      to 11 X 20 mm in size. Spots with a diameter of 1.6 mm, energy of 300 mJ,
      frequency of 1-5 Hz and in a number varying were used in relation to the extent
      of the pathology. RESULTS: In all cases, the appearance and functional results
      were good, without leaving scars and/or dyschromia. CONCLUSIONS: Erbium:YAG
      laser, in the treatment of xanthelasmas, is a parasurgical method that is simple
      to perform and because of the successful aesthetic and functional results, is a
      valid alternative to the more traditional treatment methods.

PMID- 11300636
TI  - Sclerotomy using needle puncture and subconjunctival injection of mitomycin C.
AB  - OBJECTIVE: To explore the possibilty of creating a temporary sclerotomy using a
      26-gauge needle and sustaining its patency by injectiong 0.1 mL of 0.1 mg/mL of
      mitomycin C (MMC). ANIMALS AND METHODS: Twenty-four New Zealand white rabbits
      were randomized into 3 groups. In the test group, puncture was performed using 26
      gauge needle penetrating the anterior chamber at the limbus, and 0.1 mg/mL MMC
      were injected subconjunctivally. In the control group, a puncture was performed
      in the same fashion and in the MMC group, MMC only was injected
      subconjunctivally. Intraocular pressure (IOP) was measured prior to surgery and
      at days 1, 3, 7, 10, 14, 21, and 28. RESULTS: The mean intraocular pressure in
      eyes that underwent puncture with application of MMC was significantly lower than
      the IOP in the eye at all measurements up to and including day 21. In the
      puncture group, pressure was significantly lower than in the fellow eye only at
      day 3. No significant pressure reduction was observed at any measurement interval
      in eyes treated with MMC only. CONCLUSION: This simple technique of
      subconjunctival puncture of the limbus combined with application of MMC was
      effective in lowering IOP in rabbits. This may serve to attain a temporary filter
      in patients who need strict short-term pressure control.

PMID- 11300635
TI  - GGRGDSPCA peptide: a new antiscarring agent on glaucoma filtration surgery.
AB  - BACKGROUND AND OBJECTIVE: GGRGDSPCA synthetic peptide competes for integrin
      receptor in scar formation after glaucoma filtering surgery in a rabbit model.
      The purpose of this study was to evaluate the use of this peptide and compare it
      with mitomycin on glaucoma filtering surgery. MATERIALS AND METHODS: Posterior
      sclerectomy was performed in both eyes of 17 rabbits. The right eye received
      GGRGDSPCA (p605) at 0, 4, 8, 12, and 16 days after. Nine left eyes received
      saline as a control; the remaining 8 eyes received mitomycin C at 0.5 mg/mL
      intraoperative. Intraocular pressures and biomicroscopy were evaluated as well as
      bleb function. RESULTS: Intraocular pressure decreased significantly in both the
      peptide and mitomycin treated eyes in comparison with the saline group (P =
      0.0003). Pressure was similar in both groups. The blebs showed filtrating
      function in a functional analysis at day 21 and 41 in the mitomycin cases as well
      as in the peptide group. Histologic analysis performed in both peptide and
      mitomycin groups showed inhibitory effect in fibrocellular and collagen
      organization with bleb formation. CONCLUSIONS: The p605 peptide showed to be
      similar to mitomycin C in controlling and improving glaucoma filtering surgery in
      rabbits. This alternative may potentially be useful for similar purposes in
      humans for the control of glaucoma and improvement of filtering surgery.

PMID- 11300637
TI  - Open-angle glaucoma secondary to blood clot in the Schlemm's canal following
      scleral buckle surgery and its treatment with tPA.
AB  - Obstruction of the episceral venous system can present with glaucoma. We present
      two patients who were referred to us for management of acute glaucoma with
      presumed episceral venous compression. The first patient had open-angle glaucoma
      with probable elevated episcleral venous pressure and blood in the Schlemm's
      canal, following a 360 degrees scleral buckle surgery. The second patient had
      open-angle glaucoma from delayed peribulbar hemorrhage following uncomplicated
      cataract surgery with blood in the Schlemm's canal. Both patients were
      successfully treated with intracameral injection with tissue plasminogen
      activator (tPA).

PMID- 11300638
TI  - The association of unilateral congenital glaucoma and congenital lower lid
      entropion: causal or casual?
AB  - This case documents unilateral congenital glaucoma associated with congenital
      lower lid entropion. A 2-year-old female infant was referred for evaluation and
      treatment of right-side buphthalmos caused by congenital glaucoma associated with
      bilateral congenital lower lid entropion that was prominent on the right side and
      present at birth. Examination disclosed a lower eyelid entropion of the right
      side that was treated surgically by reinserting the disinserted retractor
      aponeurosis to anterior inferior tarsal border. After three weeks, the patient
      was successfully treated with primary combined trabeculotomy-trabeculectomy for
      congenital glaucoma. The entropion of the left lower lid was asymptomatic and did
      not require any surgery. Buphthalmos caused by congenital glaucoma may be
      associated with congenital lower lid entropion and the association may be causal
      or coincidental.

PMID- 11300639
TI  - Chorioretinitis sclopetaria from BB ex memoria.
AB  - Chorioretinitis sclopetaria presents a characteristic pattern of choroidal and
      retinal changes caused by a high velocity projectile passing into the orbit, in
      close proximity to the globe. While it is unlikely that a patient should
      completely forget the trauma causing such damage, preserved or compensated visual
      function may blur the patient's memory of these events over time. Characteristic
      physical findings help to clarify the antecedent history. Despite the lack of an
      acknowledged history of ocular trauma or surgery, in our case, the characteristic
      ocular findings discovered at presentation allowed for recognition of the
      underlying etiology. Because of good visual function, the patient had completely
      forgotten about the trauma that occurred 12 years earlier. Strabismus surgery was
      performed for treatment of the presenting symptomatic diplopia. The pathognomonic
      findings in chorioretinitis sclopetaria are invaluable in correctly diagnosing
      this condition, especially when a history of ocular trauma is unavailable.

PMID- 11300640
TI  - Persistent indocyanine green angiographic findings in multiple evanescent white
      dot syndrome.
AB  - This report describes unique findings of persistent peripapillary and posterior
      pole hypofluorescence on indocyanine green angiography (ICGA) in multiple
      evanescent white dot syndrome (MEWDS). A 38-year-old woman experienced a sudden
      decrease of visual acuity in the left eye. Multiple white lesions were seen on
      fundus examination. Fluorescein angiography, indocyanine green angiography, and
      automated perimetry were performed. Fundus appearance and fluorescein angiography
      were consistent with the diagnosis of MEWDS. Automated perimetry revealed an
      enlarged blind spot. ICGA revealed a zone of hypofluorescence surrounding the
      optic disc and throughout the posterior pole. The enlarged blind spot resolved
      after seven weeks along with the signs and symptoms of MEWDS. Nine months after
      initial presentation, ICGA revealed persistent peripapillary and posterior pole
      hypofluorescence. Resolution of the enlarged blind spot and return of vision does
      not completely correlate with the disappearance of hypofluorescent areas on ICGA.
      These findings suggest that MEWDS may result in persistent abnormalities in
      choroidal circulation even after clinical symptoms resolve.

PMID- 11300641
TI  - Retrocorneal membrane after penetrating keratoplasty.
AB  - Retrocorneal membranes after penetrating keratoplasty (PKP) is a well known
      complications, resulting from unintentional retention of the host Descemet's
      membrane (DM), or donor DM detachment. We describe for the first time the
      formation of a retrocorneal inflammatory membrane that mimics donor DM detachment
      or retained recipient DM, and discuss the differential diagnosis of a
      retrocorneal membrane after PKP. Two patients who underwent PKP and subsequently
      developed a retrocorneal membrane are described. In both patients' eyes a
      retrocorneal membrane was observed immediately following penetrating
      keratoplasty. While the first patient's membrane persisted for 33 months in the
      presence of a clear graft, the second patient's membrane disintegrated and
      dissolved within two weeks following treatment with topical steroids. The first
      case describes a patient with retained Descemet's membrane, while in the second
      case, it turned out that the retrocorneal membrane was actually an inflammatory
      membrane.

PMID- 11300642
TI  - Using the eye fixation speculum as an adjunct to pterygium surgery.
AB  - A technique is described that overcomes the two biggest problems facing the
      surgeon when dissecting a pterygium from the cornea-bleeding and eye movement.
      Our technique however, requires only minimal anesthesia (topical and
      subconjunctival) and the use of a disposable speculum and suction ring. An added
      advantage is this particular speculum gives good exposure of the superior bulbar
      conjunctiva; this facilitates harvesting a conjunctival autograft.

PMID- 11300643
TI  - A novel approach for the fixation of enucleated eyes during microsurgical
      procedures using common household plumbing accessories.
AB  - The authors describe a novel approach for the fixation of enucleated eyes during
      microsurgical procedures using common household plumbing accessories. The device
      consists of a ring adaptor with 4 round-ended screws placed horizontally at its
      sides and a plastic hose connector. The enucleated globe is secured in the center
      of the ring adaptor by gently tightening the screws. The hose connector supports
      the posterior pole of the globe and is secured onto a styrofoam board that
      provides a platform for resting the surgeon's hands. The device proved very
      satisfactory to residents during the teaching of cataract surgery and
      trabeculectomy on porcine eyes. Our globe fixation device is simple, inexpensive,
      effective, and readily available. It may be especially useful in developing
      countries.

PMID- 11300644
TI  - Corneal topography changes after vitreoretinal surgery.
AB  - The authors report the results of a prospective study to assess corneal
      topography changes after vitreoretinal surgery procedures. Computer-assisted
      videokeratography using a Topographic Modeling System-1 (TMS-1) were
      prospectively performed before and after vitreoretinal surgery (vitrectomy with
      or without scleral buckling) in 12 eyes (patients) with varied vitreoretinal
      pathology, including cytomegalovirus (CMV) retinitis, CMV-related retinal
      detachment, retinal detachment with and without proliferative vitreoretinopathy,
      trauma, acute retinal necrosis, and macular hole. Preoperative and postoperative
      surface regularity index (SRI), surface asymmetry index (SAI), and induced
      astigmatism were determined. Patients were followed for an average of 6 months
      (range: 2-15 months). Mean preoperative SRI was 0.52 (0.05-1.06) and
      postoperative SRI was 0.73 (0.25-1.36). Mean preoperative SAI was 0.43 (0.22
      0.93) and postoperative SAI was 0.56 (0.21-0.99). Mean induced astigmatism was
      0.7 diopters. Our study suggests that the central corneal optical quality (SRI)
      and the asymmetricity of the anterior corneal curvature (SAI) deteriorates after
      vitreoretinal surgery.

PMID- 11300645
TI  - The superior and inferior components of Whitnall's ligament.
AB  - During an orbital dissection in a 60-year-old white male, we came across a very
      well defined superior and inferior component of Whitnall's ligament (Figure 1).
      The superior component of Whitnall's ligament is well described and well known to
      ophthalmologists performing eyelid surgery. The inferior component, however, is
      not well recognized or described. This cadaver dissection illustrates both
      Whitnall's components well.

PMID- 11300646
TI  - Three-dimensional analysis of macular diseases with a scanning retinal thickness
      analyzer and a confocal scanning laser ophthalmoscope.
AB  - OBJECTIVE: To compare three-dimensional analysis of macular diseases obtained
      using the scanning retinal thickness analyzer (RTA) with that obtained using the
      confocal scanning laser ophthalmoscope, Heidelberg Retina Tomograph (HRT).
      PATIENTS AND METHODS: Both the RTA and the HRT were used to examine 50 eyes of 36
      patients with diabetic macular edema, macular edema following branch retinal vein
      occlusion, age-related macular degeneration, and idiopathic macular holes.
      RESULTS: In most macular diseases, the retinal thickness map constructed using
      the RTA agreed with the image obtained with the HRT. The two maps were not
      consistent with each other, however, in patients with dense retinal hemorrhages
      and with extrafoveal fixation. CONCLUSIONS: Although both the RTA and the HRT
      give additional information to clinically evaluate macular diseases, they do have
      limitations. The discrepancy between these two analyses in some specific macular
      pathologies might be caused by the different wavelengths of the laser beam and
      the different methodologies used to scan the retina.

PMID- 11300647
TI  - Comparison of cardiac and regional hemodynamic responses to N-methyl-L-arginine
      and aminoguanidine infusions in conscious pigs.
AB  - The aim of this study was to elucidate cardiac and regional hemodynamics using a
      nonspecific inhibitor of the constitutive and inducible nitric oxide synthase
      (NOS), N-methyl-L-arginine (L-NMA), and a specific inhibitor of the inducible
      NOS, aminoguanidine, in conscious pigs. Animals were divided into two groups.
      After hemodynamics were stabilized, animals in group 1 (n = 5) received an
      infusion of L-NMA at 300 microg/kg per min, i.v., over 60 min, and group 2 (n =
      5) received an infusion of aminoguanidine, infused at 1 mg/kg per min over 60
      min. Hemodynamic parameters including arterial blood pressure, heart rate,
      cardiac output, dP/dt, and carotid, coronary, hepatic, portal, mesenteric, and
      renal blood flows were continuously recorded before and 5, 15, 30, 45, 60, and
      120 min after L-NMA infusion or aminoguanidine infusion, or both. The L-NMA
      vasopressor response (20%) was associated with a significant increase in systemic
      vascular resistance (45%). Carotid, hepatic, and renal vascular resistance
      increased significantly by 95%, 110%, and 20%, respectively, at 60 min after L
      NMA infusion. Finally, heart rate, cardiac output, dP/dt, and portal and
      mesenteric blood flows remained unchanged after L-NMA infusion. In contrast,
      aminoguanidine infused at 1 mg/kg per min over 60 min did not change systemic
      arterial blood pressure or regional blood flow in conscious pigs. Furthermore,
      aminoguanidine had no effect on acetylcholine vasodilator effects. In conclusion,
      the lack of pressor effects and of agonist-stimulated NO production induced by
      aminoguanidine suggests that aminoguanidine is a weak inhibitor of the
      constitutive NOS. Compared with L-NMA, the selectivity of aminoguanidine may
      decrease possible side effects that could occur as a result of inhibition of
      constitutive NOS.

PMID- 11300648
TI  - Comparison of a vasopeptidase inhibitor with neutral endopeptidase and
      angiotensin-converting enzyme inhibitors on bradykinin metabolism in the rat
      coronary bed.
AB  - The in vitro effects of omapatrilat, a dual vasopeptidase inhibitor that
      simultaneously inhibits neutral endopeptidase (NEP) and angiotensin-converting
      enzyme (ACE), on exogenous bradykinin metabolism after a single passage through
      the coronary bed were compared with that of a NEP inhibitor (retrothiorphan, 25
      nM), an ACE inhibitor (enalaprilat, 130 nM), and omapatrilat (25 nM). Bradykinin
      and inhibitors were infused into isolated Langendorff rat hearts perfused at 1
      ml/min followed by reperfusion at 10 ml/min. Residual bradykinin was quantified
      in the coronary effluent by enzyme-linked immunosorbent assay to calculate
      bradykinin recovery and its kinetic parameters (Vmax/Km). Bradykinin degradation
      rate at 1 ml/min was 4.56 +/- 0.39 1/min per gram without inhibitors and was
      significantly reduced to 2.57 +/- 0.19 1/min per gram in the presence of
      enalaprilat, to 2.97 +/- 0.38 1/min per gram with retrothiorphan, to 1.82 +/-
      0.17 1/min per gram with both enalaprilat and retrothiorphan, and to 1.14 +/-
      0.35 1/min per gram with omapatrilat. In a second set of experiments, the effect
      of a 14-day treatment of rats with either ACE inhibitors (enalapril, quinapril,
      and ramipril), a NEP inhibitor (candoxatril), or omapatrilat on exogenous
      bradykinin metabolism was studied in Langendorff perfused hearts isolated from
      these long-term treated rats. In untreated rats, bradykinin degradation at a
      coronary perfusion of 1 ml/min was 4.35 +/- 0.41 1/min per gram. This value was
      reduced by 30% for the NEP inhibitor, by 50% for all ACE inhibitors, and by 75%
      for omapatrilat. All inhibitors administered either short term or long term
      significantly reduced bradykinin degradation during a single passage through the
      coronary bed. However, omapatrilat administration resulted in the greatest
      protection from bradykinin breakdown than ACE or NEP inhibitors alone.

PMID- 11300649
TI  - Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by
      opening ATP-sensitive potassium channels.
AB  - Levosimendan, a novel calcium sensitizer developed for the treatment of acute
      heart failure, is an inodilator that increases coronary flow. Because it was
      recently shown that levosimendan stimulates potassium current through K(ATP)
      channels in isolated rat arterial cells, our aim was to assess whether the
      levosimendan-induced increase in coronary flow is due to the opening of the
      K(ATP) channels in coronary smooth muscle. The effect of levosimendan on the
      diastolic coronary flow velocity (DCFV) was measured in the Langendorff perfused
      spontaneously beating guinea-pig heart in the absence and presence of
      glibenclamide. Pinacidil was used as a reference compound, and the protein kinase
      C inhibitor bisindolylmaleimide was used to study the dilatory effect of
      levosimendan when the K(ATP) channels in smooth muscle are not inhibited by PKC
      dependent phosphorylation. Levosimendan (0.01-1 microM) increased DCFV
      concentration-dependently and was noncompetitively antagonized by 0.1 microM
      glibenclamide, whereas pinacidil was inhibited competitively by glibenclamide. In
      the presence of glibenclamide the positive inotropic and chronotropic effects of
      levosimendan were unaltered. The effect of bisindolylmaleimide and levosimendan
      on DCFV was additive. The results indicate that levosimendan induced coronary
      vasodilation through the opening of the K(ATP) channels. Levosimendan and
      pinacidil probably have different binding sites on the K(ATP) channels. The
      additive effect of bisindolylmaleimide and levosimendan on the increase of DCFV
      suggests that the latter binds to the unphosphorylated form of the channel.

PMID- 11300650
TI  - Effects of olprinone, a phosphodiesterase 3 inhibitor, on regional cerebral blood
      flow of cerebral cortex in stroke patients.
AB  - The effects of olprinone (0.2 microg/kg per minute, i.v.) on cerebral blood flow
      were examined using technetium-99m-ethyl cysteinate dimer (99mTc-ECD) brain
      single-photon emission computed tomography in 14 stroke patients (69.0 +/- 5.6
      years) and 12 normal subjects (68.1 +/- 6.2 years). The regional cerebral blood
      flow of the cerebral cortex was measured at six sites for each stroke patient
      (stroke group: n = 68, excluding 16 infarct areas confirmed on computed
      tomography image) and for each normal subject (normal group: n = 72). 99mTc-ECD
      brain single-photon emission computed tomography was repeated as the baseline 7
      days after olprinone treatment study. The percent increment of the rCBF was 14.4
      +/- 9.8% in the normal group and 10.7 +/- 11.7% in the stroke group (p = 0.002).
      The baseline value of the regional cerebral blood flow had a significant negative
      correlation with the increase of the regional cerebral blood flow in the normal
      group (r = -0.73, p < 0.0001) and in the stroke group (r = -0.43, p < 0.001).
      Although olprinone could dilate the cerebral vessels of stroke patients as well
      as those of normal subjects, smooth muscle dysfunction of the cerebral vessels
      due to advanced arteriosclerosis may reduce this effect.

PMID- 11300651
TI  - Effects of radiation therapy on vascular responsiveness.
AB  - The use of radiation therapy to inhibit vascular proliferative diseases has
      produced encouraging results in several clinical trials. However, little is known
      about the possible side effects of radiation on vascular responsiveness. Our goal
      was to study the in vitro vascular responses of the rabbit aorta to various
      agonists immediately after several regimens of radiation therapy administered at
      doses prescribed in clinical protocols and at two different dose rates. High-dose
      rate radiation was administered either by brachytherapy, using a gamma source,
      iridium 192, or an external electron beam producing beta radiation. Low-dose-rate
      radiation was administered by brachytherapy using a liquid-filled balloon with
      the beta emitter 32P. Vascular reactivity after the various regimens of
      irradiation was determined using the organ bath pharmacology assay. Various
      agonists were applied to the rabbit aorta to produce full cumulative
      concentration-response curves. Radiation, administered using an external electron
      beam, did not alter endothelium-dependent relaxation of the aorta induced by
      acetylcholine. However, the use of a catheter-based system to deliver radiation
      disrupted the endothelial cell lining of the vessel, causing a lack of relaxation
      by acetylcholine. Therefore, to compare all modalities of radiation therapy on
      vascular responsiveness, the agonists used in this study are known to act
      directly on the smooth muscle. Radiation therapy had no effect on the contractile
      responses induced by the following agonists: phenylephrine and potassium
      chloride. Vascular dilatation induced by nitroglycerin, a nitric oxide donor, was
      unaffected by radiation therapy. The contractile response induced by des-Arg9
      bradykinin, a kinin B1 receptor agonist, was significantly increased twofold to
      threefold by all types of irradiation under study. This enhanced response is
      attributable to an increase of mRNA levels coding for this receptor. In all
      cases, radiation therapy did not alter the effective concentration producing 50%
      of maximal responsiveness (EC50) and did not reduce the vascular responsiveness
      induced by agonists. Taken together, we conclude that radiation therapy does not
      hinder endothelium-independent vascular responsiveness and increases the kinin B1
      receptor-mediated vasoconstriction.

PMID- 11300652
TI  - Effect of the blood substitute diaspirin crosslinked hemoglobin in rat mesenteric
      and human radial collateral arteries.
AB  - The actions of the blood substitute diaspirin crosslinked hemoglobin (DCLHb) were
      investigated in rat (small mesenteric artery) and human (radial collateral
      artery) resistance vessels mounted in a wire myograph for isometric tension
      recording. DCLHb did not contract resting vessels from rats, but vasoconstrictor
      responses were observed in isolated arteries and perfused mesenteric beds
      prestimulated with threshold concentrations of methoxamine. The DCLHb contractile
      responses were greatly attenuated by N(G)-nitro-L-arginine methyl ester
      hydrochloride (L-NAME) or endothelial removal, whereas BQ-123 (endothelin A
      receptor antagonist), prazosin (alpha1-adrenoceptor antagonist), or indomethacin
      (cyclooxygenase inhibitor) had no effect. Endothelium-dependent relaxations to
      carbachol in both rat mesenteric and human radial collateral artery were
      inhibited by DCLHb. Relaxations to carbachol were studied in the presence of L
      NAME or 25 mM KCl to investigate the effect of DCLHb on endothelium-derived
      hyperpolarizing factor (EDHF) and nitric oxide, respectively. In both rat and
      human vessels, EDHF-mediated relaxations were not affected by DCLHb
      preincubation, whereas the nitric oxide component of carbachol-induced
      relaxations was practically abolished. In conclusion, inhibition of the effects
      of basal nitric oxide release underpins the vasoconstrictor effects of DCLHb.
      DCLHb effectively abolishes the nitric oxide component of carbachol-induced
      relaxation, with no effect on the EDHF-mediated component in both isolated rat
      mesenteric and human radial collateral arteries.

PMID- 11300654
TI  - Modulation of human platelet aggregation by the phosphodiesterase type 5
      inhibitor sildenafil.
AB  - The aim of this study was to investigate if the phospodiesterase type 5 inhibitor
      sildenafil inhibits collagen- or ADP-induced human platelet aggregation and
      bleeding time. To investigate this, two studies were designed. In the first, a
      single oral dose of sildenafil, 100 mg, was administered to healthy men. Bleeding
      time was determined and agonist (ADP and collagen)-induced platelet aggregation
      (ex vivo in platelet rich plasma) was measured 0, 1, and 4 h after application.
      In the second, a single oral dose of sildenafil, 50 mg, was administered and, in
      addition to the parameters in the first study, we also determined the platelet
      aggregation after 24 h and measured the effect of a nitric oxide donor (S-nitroso
      N-acetylpenicillamine [SNAP]) in combination to mimic a physiologic nitric oxide
      release from the endothelium. The bleeding time of 1 h after sildenafil
      medication (100 mg) was significantly prolonged but recovered toward control
      values after 4 h, whereas application of sildenafil at a lower dose (50 mg) did
      not alter the bleeding time. Sildenafil (100 and 50 mg) did not inhibit the ADP
      induced aggregation, whereas the collagen-induced aggregation (100 mg) was
      markedly reduced after 1 h and significantly inhibited 4 h after application.
      This inhibitory effect was overcome by higher concentrations of collagen. SNAP
      (0.5 microM) induced an inhibition of platelet aggregation that was potentiated
      after taking sildenafil (50 mg, 1 and 4 h afterward) and abrogated after 24 h.
      These data indicates that sildenafil may inhibit collagen-induced platelet
      aggregation ex vivo. After co-administration of nitric oxide, collagen- and ADP
      induced platelet aggregation was significantly inhibited, which may reflect
      physiologic conditions of an in vivo system.

PMID- 11300653
TI  - Inhibition of platelet activation in stroke-prone spontaneously hypertensive
      rats: comparison of losartan, candesartan, and valsartan.
AB  - In vitro studies have suggested that losartan interacts with the thromboxane
      (TxA2)/ prostaglandin H2 (PGH2) receptor in human platelets, reducing TxA2
      dependent platelet activation. The aim of this study was to evaluate the effect
      of different angiotensin II type 1 receptor antagonists in stroke-prone
      spontaneously hypertensive rats (SHRSP). The level of platelet activation was
      assessed by determining P-selectin expression in platelets by flow cytometry. The
      ex vivo adhesion of platelets was also analyzed. The number of platelets that
      expressed P-selectin in SPSHR was significantly increased (% P-selectin
      expression: WKY 4 +/- 0, 4%; SHRSP 15.5 +/- 0, 8% [n = 8], p < 0.05). In SHRSP
      receiving losartan (20 mg/kg body weight per day) the percentage of platelets
      expressing P-selectin fell to levels close to that observed in WKY. The number of
      platelets from SHRSP treated with valsartan and candesartan (20 mg/kg body weight
      per day for 14 days) that expressed P-selectin was not significantly different
      from those from untreated SPRHR. Only losartan treatment reduced ex vivo platelet
      adhesion to a synthetic surface. The antiplatelet effect of losartan does not
      appear to be related to the level of blood pressure reduction. In ex vivo
      experiments, losartan significantly reduced the binding of the radiolabeled TxA2
      agonist U46619 to platelets obtained from SHRSP in a dose-dependent manner.
      Treatment with losartan reduced the number of activated platelets in SHRSP
      independently of its blood pressure effects. TxA2-receptor blockade is proposed
      as a mechanism by which losartan can prevent platelet activation.

PMID- 11300655
TI  - Prevention of cerebral thromboembolism by low-dose anticoagulant therapy in
      atrial fibrillation with mitral regurgitation.
AB  - Controversy exists regarding the influence of mitral regurgitation (MR) on
      thromboembolic risk in patients with atrial fibrillation. We aimed to investigate
      retrospectively a reduction of risk for stroke due to MR in atrial fibrillation
      and to evaluate the effectiveness of low-intensity anticoagulation therapy. In
      313 patients with atrial fibrillation, transthoracic echocardiography was
      performed and MR was graded. Between the groups with no or mild MR (n = 209) and
      with moderate or severe MR (n = 104), age, sex, treatment, history of diabetes,
      hypertension, hyperlipemia and mitral stenosis, and previous stroke were
      compared. No significant differences in clinical characteristics, treatment, or
      history were observed between the two groups. The incidence of thromboembolism
      was significantly higher in the group with no MR (48 patients [23%]) than in the
      group with MR (14 patients [13%], p < 0.05). In the MR group, previous stroke was
      frequently observed in patients without warfarin treatment (11 of 51 patients)
      compared with patients with low-dose warfarin treatment (international normalized
      ratio of 1.6-1.8) (3 of 53 patients, p < 0.05). Consequently, the thromboembolic
      event was markedly prevented by low-dose warfarin treatment.

PMID- 11300656
TI  - KT3-671, an angiotensin AT1 receptor antagonist, attenuates vascular but not
      cardiac responses to sympathetic nerve stimulation in pithed rats.
AB  - Effects of KT3-671 on vascular and cardiac sympathetic neurotransmission were
      investigated in pithed rats. The pressor response to spinal stimulation (5 Hz) of
      the pithed rat without the adrenals was approximately 75% of that with the
      adrenals. Guanethidine (8 mg/kg, i.v.) decreased by about 76% the pressor
      response to sympathetic stimulation in the pithed rat with intact adrenals and
      the guanethidine-resistant response was almost completely abolished by bilateral
      adrenalectomy. Therefore, the following experiments were done using the pithed
      rat without the adrenals. KT3-671 (1-10 mg/kg, i.v.) as well as losartan (1-10
      mg/kg, i.v.) inhibited dose-dependently the pressor response to sympathetic
      stimulation. KT3-671 was approximately four times more potent than losartan in
      inhibiting the pressor response. The two angiotensin II subtype 1 receptor
      antagonists (10 mg/kg, i.v.) did not affect the pressor response to exogenously
      administered norepinephrine. Neither KT3-671 nor losartan influenced the
      tachycardia induced by spinal stimulation and isoprenaline. Intravenous infusion
      of angiotensin II (100 ng/kg/min) did not affect both pressor and tachycardic
      responses to sympathetic stimulation. In conclusion, KT3-671 as well as losartan
      inhibits vascular but not cardiac sympathetic neurotransmission of the pithed
      rats, which may contribute to its overall antihypertensive efficacy.

PMID- 11300657
TI  - Downregulation of the AT1A receptor by pharmacologic concentrations of
      Angiotensin-(1-7).
AB  - Angiotensin (Ang)-(1-7), the amino terminal heptapeptide fragment of Ang II, is
      an endogenous Ang peptide with vasodilatory and antiproliferative actions.
      Because Ang II causes vasoconstriction and promotes growth through activation of
      Ang type 1 (AT1) receptors, we investigated whether the actions of Ang-(1-7) are
      due to its regulation of these receptors. Studies were performed in CHO cells
      stably transfected with the AT1A receptor. Ang-(1-7) competed poorly with [125I]
      Ang II for the AT1A binding site and was ineffective at shifting the IC50 for Ang
      II competition with [125I]-Ang II for binding to the AT1A receptor. However, if
      CHO-AT1A cells were pretreated with Ang-(1-7) and then treated with acidic
      glycine to remove surface-bound ligand, the heptapeptide caused a concentration
      dependent reduction in Ang II binding, with a maximal inhibition to 67.8 +/- 4.6%
      of total (p < 0.05) at 1 microM Ang-(1-7) compared with a reduction to 24% of
      total by 10 nM Ang II. Ang-(1-7) pretreatment caused a small but significant
      decrease in the affinity of [125I]-Ang II for the AT1A receptor and a significant
      reduction in the total number of binding sites. The Ang-(1-7)-induced reduction
      in binding was rapid (occurring as early as 5 min after exposure to the peptide),
      was maintained for 30 min during continued exposure of the cells to Ang-(1-7),
      and rapidly recovered after removal of the heptapeptide. The AT1 receptor
      antagonist L-158,809 reduced the Ang-(1-7)-induced downregulation of the AT1A
      receptor, suggesting that interactions with AT1A receptors mediate the regulatory
      events. Pretreatment with 1 microM or 10 microM Ang-(1-7) significantly reduced
      inositol phosphate production in response to 10 nM Ang II. The decrease in
      binding and responsiveness of the AT1A receptor after exposure to micromolar
      concentrations of Ang-(1-7) suggests that the heptapeptide downregulates the AT1A
      receptor to reduce responses to Ang II. Because downregulation of the receptor
      only occurred at micromolar concentrations of the heptapeptide, our findings
      suggest that Ang-(1-7) is not a potent antagonist at the AT1A receptor. However,
      when the balance between Ang II and Ang-(1-7) is shifted in favor of Ang-(1-7),
      such as during inhibition of Ang-converting enzyme, some contribution of this
      mechanism may come into play.

PMID- 11300658
TI  - Inhibition of the acute effects of angiotensin II by the receptor antagonist
      irbesartan in normotensive men.
AB  - Irbesartan (SR 47436, BMS 186295) is an imidazole derivative that specifically
      binds to the angiotensin type 1 receptor. The purpose of this study was to assess
      the inhibitory effect of irbesartan on the pressor action of exogenous
      angiotensin II in healthy subjects, to evaluate the dose dependency and duration
      of this inhibition, and to determine the effect of irbesartan on plasma
      components of the renin-angiotensin system. Forty-two healthy male volunteers
      maintained on ad libitum sodium intake were enrolled in a randomized, double
      blind, placebo-controlled, parallel-design, dose-ranging study. On 2 study days 1
      week apart, volunteers were given either a placebo or the active drug at one of
      the chosen doses (5, 25, 50, 75, 100, 150, or 300 mg). The pressor effects of an
      individually titrated test dose of exogenous angiotensin II as well as plasma
      levels of angiotensin II, active renin, aldosterone, and treatment drug were
      determined before and throughout the 24 h after drug administration. The
      inhibitory effect of irbesartan on the pressor response to angiotensin II was
      observed within 1 h after dosing, peaked between 2 and 4 h, and lasted more than
      24 h for doses of 25 mg and more. The effect was clearly dose related. Two and 24
      h after administration of irbesartan, 300 mg, the response of arterial blood
      pressure (systolic and diastolic) to a given dose of angiotensin II was reduced
      by approximately 100% and 60%, respectively. Plasma concentrations of angiotensin
      II and active renin increased markedly after irbesartan administration, whereas
      plasma concentrations of aldosterone decreased. No evidence was found that the
      high levels of circulating angiotensin II observed after irbesartan
      administration could override the inhibitory effect of irbesartan on any of the
      measured parameters up to 24 h after dose. In conclusion, irbesartan appears to
      be a well-tolerated, orally active, potent antagonist of the renin-angiotensin
      system in men.

PMID- 11300659
TI  - Effects of bradykinin on renal nerve stimulation-induced antidiuresis and
      norepinephrine overflow in anesthetized dogs.
AB  - We examined effects of bradykinin on antidiuresis and norepinephrine overflow
      induced by renal nerve stimulation (RNS) in anesthetized dogs, with or without
      blockade of the B2 receptor by Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7,
      Oic8]bradykinin) or the endogenous nitric oxide generation by N(G)nitro-L
      arginine (NOARG), a nitric oxide synthase inhibitor. RNS (0.5-2.0 Hz) produced
      significant decreases in urine flow, urinary and fractional excretions of sodium,
      and increases in norepinephrine secretion rate (NESR), without affecting systemic
      and renal hemodynamics. Intrarenal arterial infusion of bradykinin (5 ng/kg per
      minute) significantly suppressed the RNS-induced antidiuresis and increase in
      NESR. Hoe 140 (100 ng/kg per minute) did not affect the RNS-induced renal
      actions, but in the presence of Hoe 140, bradykinin-induced suppressive actions
      on reductions in urine formation and increases in NESR in response to RNS were
      abolished. RNS during intrarenal arterial infusion of NOARG (40 microg/kg per
      minute) led to potent reductions in urine formation and decreased renal blood
      flow and glomerular filtration rate. Simultaneously, NESR was markedly increased.
      During NOARG infusion, bradykinin-induced decreases in renal actions elicited by
      RNS were markedly attenuated. These findings suggest that bradykinin suppresses
      the RNS-induced norepinephrine overflow and renal actions via nitric oxide
      production mediated by activation of B2 receptor. Renal noradrenergic
      neurotransmission may be inhibited by bradykinin at the prejunctional level, when
      its local production in the kidney is enhanced.

PMID- 11300660
TI  - Pharmacologic characterization of S-1255, a highly potent and orally active
      endothelin A receptor antagonist.
AB  - The pharmacologic properties of a novel nonpeptide endothelin (ET) receptor
      antagonist, S-1255 ([R]-[+]-2-[benzo(1,3)dioxol-5-yl]-6-isopropyl-4-[4
      methoxyphenyl]-2H-chromene-3-carboxylic acid), was studied. [3H]S-1255
      specifically bound to porcine aortic smooth muscle membranes expressing only
      ET(A) receptors with a Kd value of 0.39 nM. [3H]S-1255 binding was potently
      inhibited by ET-1 and selective ET(A) or ET(A)/ET(B) receptor antagonists, such
      as L-749329, SB209670, bosentan, and BQ-123, but the inhibitory effect of ET-3
      and the selective ET(B) receptor antagonist, BQ-788, on the binding was weak.
      These inhibitory effects on [3H]S-1255 binding correlated well with those on
      [125I]ET-1 binding. S-1255 inhibited ET(A) receptor- and ET(B) receptor-mediated
      contractions in isolated rabbit femoral and pulmonary arteries with pA2 values of
      8.8 and 6.3, respectively. The pA2 value of S-1255 for ET(B) receptor-mediated
      relaxation in isolated rabbit mesenteric artery was 7.4. Oral administration of S
      1255 (0.3-10 mg/kg) caused dose-dependent inhibition of the pressor response to
      exogenous ET-1 (0.1 nmol/kg) in conscious normotensive rats, which was similar to
      that produced by intravenous administration (1 and 3 mg/kg). S-1255 (10 and 30
      mg/kg, p.o.) significantly reduced blood pressure in deoxycorticosterone acetate
      salt hypertensive rats from 6 h after administration, and the hypotensive effects
      were sustained up to 24-48 h. These results suggest that S-1255 is a highly
      potent and orally active ET(A) receptor antagonist.

PMID- 11300661
TI  - Therapeutic administration of an endothelin-A receptor antagonist after acute
      ischemic renal failure dose-dependently improves recovery of renal function.
AB  - Endothelin (ET) is known to reduce glomerular filtration rate and renal blood
      flow and is a possible mediator of acute renal failure (ARF). We recently
      demonstrated that the administration of a very high dose of the ET(A)-receptor
      antagonist LU 135252 (LU) accelerates recovery from postischemic acute renal
      failure by an improvement of renal perfusion in a rat model. The aim of this
      study was to investigate whether this effect of LU is dose dependent. ARF was
      induced in rats by clamping both renal arteries. Serum creatinine was measured
      and endogenous creatinine clearance and fractional sodium excretion were
      calculated up to 4 days after acute ischemia. Rats were treated either with the
      selective ET(A)-receptor antagonist LU or with vehicle only after reperfusion. LU
      in doses of 0.5, 1, or 5 mg/kg per day was infused via a femoral vein using an
      osmotic minipump. Serum creatinine was increased approximately eightfold after
      induction of ARF. Creatinine clearance decreased from 4.35 +/- 0.26 ml/min before
      acute renal failure to 0.15 +/- 0.02, 0.54 +/- 0.1, and 1.49 +/- 0.19 ml/min on
      days 1, 2, and 4 after ischemia (p < 0.05). Fractional sodium excretion increased
      from baseline 0.77 +/- 0.05% to 7.5 +/- 1.21 % on day 1 and 8.53 +/- 1.34% on day
      2 (p < 0.05). Treatment with LU improved kidney function dose relatedly. There
      was no significant change in creatinine clearance, but compared with controls,
      with doses of 0.5 mg/kg per day and 1 mg/kg per day (0.28 +/- 0.1, 0.88 +/- 0.22,
      and 1.93 +/- 0.24 ml/min on days 1, 2, and 4), we noted a significant increase
      under 5 mg/kg per day (day 1: 0.62 +/- 0.17 ml/min; day 2: 1.38 +/- 0.26 ml/min;
      and day 4: 2.45 +/- 0.21 ml/min; p < 0.05). Fractional sodium excretion decreased
      dose-relatedly to a maximally 2.48 +/- 0.58% on day 1 and 2.25 +/- 0.71 % on day
      2 after treatment with the highest dose when compared with untreated control rats
      (p < 0.05). Our data support the hypothesis that ET plays a major role in ARF. It
      can be concluded from these results that recovery from ischemic ARF is
      significantly and dose-dependently enhanced by treatment with a selective ET(A)
      receptor antagonist.

PMID- 11300662
TI  - Plasma levels of asymmetrical dimethyl-L-arginine in patients with congenital
      heart disease and pulmonary hypertension.
AB  - Asymmetrical dimethyl-L-arginine (ADMA) is an endogenous inhibitor of nitric
      oxide synthase. We hypothesized that plasma levels of ADMA could be increased in
      patients with congenital heart disease and pulmonary hypertension. Cardiac
      catheterization was performed in 20 children and young adults with congenital
      heart disease with a median age of 10 years (range, 4 months to 33 years). The
      patients were assigned to group I (high flow, low pressure; n = 14) when Qp/Qs
      was 1.5 or greater and the mean PAP was less than 25 mm Hg or to group II (high
      pressure, high resistance; n = 6) when the mean PAP was greater than 25 mm Hg and
      Rp/Rs was greater than 0.3. Blood samples were taken from pulmonary vein or left
      ventricle. ADMA was measured by high-performance liquid chromatography. In
      addition, levels of ADMA were measured in peripheral venous blood obtained from
      eight control patients. Levels of ADMA in control patients (median, 0.21
      microM/l; range, 0.08-0.27 microM/l) did not differ from levels obtained in group
      I (median, 0.30 microM/l; range, 0.06-0.49) microM/l). Patients in group II
      showed increased plasma levels of ADMA (median, 0.55; range, 0.25-0.79) (p <
      0.01). Inhibition of nitric oxide synthase by increased levels of ADMA might
      contribute to pulmonary hypertension in patients with congenital heart disease.

PMID- 11300663
TI  - Predictors of depression in a sample of African-American homeless men:
      identifying effective coping strategies given varying levels of daily stressors.
AB  - In a sample of African-American, homeless or insecurely sheltered men, the
      occurrence of discrete stressors in the prior week contributed to the experience
      of depressive symptoms among this generally stressed population. Reliance on
      active, problem-focused coping strategies as opposed to emotion-coping strategies
      was associated with lower levels of depressive symptoms contradicting the
      hypothesis that active coping is counter-productive for African-American men.
      However, depressive symptoms increased, with added uncontrollable stress, even
      for active copers, contradicting a stress-buffering hypothesis. Under conditions
      of high uncontrollable stress, problem-focused coping was associated with lower
      levels of depressive symptoms than emotion-focused coping, however, additional
      discrete stressors exerted less impact on the level of depressive symptoms among
      the emotion-focused copers than the active, problem-focused copers.

PMID- 11300664
TI  - The use and misuse of some positively valenced community concepts.
AB  - Considers the usage of four somewhat amorphous, but positively valenced,
      community mental health terms: primary prevention in mental health (and closely
      related notions such as wellness enhancement and positive psychology);
      resilience; charter schools; and empowerment. Use of these concepts often
      reflects a need to align with currently popular, "in"-terminology, rather than an
      intrinsic connection between what is being written about and a tight definition
      of the concept in question. Usages built primarily around a concept's positive
      valence and glitter tend to: (a) break down communication; (b) confuse rather
      than clarify; and (c) ultimately retard a field's growth and progress.

PMID- 11300665
TI  - Diagnosing depression in African Americans.
AB  - Since the 1970s, articles have noted the increased presence of psychotic symptoms
      among depressed African Americans, the presence of diagnostic bias identified
      when structured clinical interviews are used, and the identification of
      misdiagnosis of affective illness among chronically, mentally ill, African
      Americans. This paper reviews this literature and describes three alternative
      presentations of depressive illness among African Americans that differ from the
      DSM IV criteria for Major Depressive Disorder: "the stoic believer," "the angry,
      'evil' one" with a personality change, and "the John Henry doer." Clinicians are
      encouraged to recall these presentations of depression when evaluating African
      American patients.

PMID- 11300666
TI  - Moderators of stress in parents of children with autism.
AB  - Parents of children with autism experience more stress and are more susceptible
      to negative outcomes than parents of children with other disabilities. The
      present work examines the relationship between stressors, social support, locus
      of control, coping styles, and negative outcomes (depression, social isolation,
      and spousal relationship problems) among parents of children with autism. Fifty
      eight parents completed surveys. Results indicated that several coping styles
      corresponded to negative outcomes. Furthermore, the relationship between
      stressors and negative outcomes was moderated by social support and coping style.
      Results are discussed in relation to applications for clinical practice.

PMID- 11300667
TI  - Determinants of service placements for youth with serious emotional and
      behavioral disturbances.
AB  - This paper examines the association between race and type of service placement
      for youth with serious emotional and behavioral disturbances. Placements were
      reviewed for 2,803 black and white youth served in the community mental health
      system. Differences were found between black and white youth in the type of out
      of-home placements they received after controlling for sociodemographic variables
      and presenting problems. Black youth were more likely than whites to be placed in
      correctional facilities and foster care while white youth were more likely than
      blacks to be hospitalized (p < .001). This variation in placement may not be
      clinically warranted. Placement criteria and outcome assessments are needed.

PMID- 11300668
TI  - Compliance and costs in a case management model.
AB  - Case management (CM) team models are a well-established mode for delivery of
      mental health services to individuals with serious and persistent mental
      illnesses. Although numerous aspects of CM models have been investigated, a
      neglected component is compliance to outpatient appointments. This pilot, quality
      assurance study examined the relationship between compliance to psychiatric
      outpatient appointments and costs in an integrated service delivery system using
      CM for treating seriously and persistently mentally ill individuals. Two groups
      of participants were randomly selected based on a single compliance data point
      and examined using cross-sectional and longitudinal methods. Results revealed
      relatively high compliance rates that were significantly different between groups
      over time. However, no differences in costs for services over time, and no
      demographic variables predictive of noncompliance (i.e., age, miles from
      residence to site, ethnicity, diagnostic group, level of functioning) were
      identified. Implications for CM in public mental health integrated service
      delivery systems, and quality assurance studies are discussed.

PMID- 11300669
TI  - The use of radiotelemetry in small laboratory animals: recent advances.
AB  - Radiotelemetry provides an alternative means of obtaining physiological
      measurements from awake and freely moving laboratory animals, without introducing
      stress artifacts. For researchers, especially those in the fields of pharmacology
      and toxicology, the technique may provide a valuable tool for predicting the
      effectiveness and safety of new compounds in humans. In light of studies
      described in the literature, it is concluded that there is ample evidence that
      the use of radiotelemetry for measuring blood pressure, cardiac activity, heart
      rate, body temperature, and locomotor activity in rodents has been validated
      sufficiently. Today, this technology is an important tool for the stress-free
      collection of these physiologic data in small rodents, including mice.

PMID- 11300670
TI  - The effects of routine cage-changing on cardiovascular and behavioral parameters
      in male Sprague-Dawley rats.
AB  - The objective of this study was to determine whether the blood pressure and heart
      rate of adult male Sprague-Dawley rats are affected by the routine animal
      husbandry procedure of moving animals to clean cages. Cardiovascular parameters
      were obtained by using radiotelemetry; behavior in the home cage also was
      evaluated. Each rat had a radiotelemetry transmitter implanted in the peritoneal
      cavity, with the attached catheter placed in the femoral artery. After a 7- to 9
      day recovery period, half of the rats were moved to clean cages with fresh wood
      chip bedding; the other animals were left undisturbed. Systolic, diastolic, and
      mean arterial blood pressures; heart rate; and cage behavior (movement, rearing,
      grooming) increased promptly and significantly when animals were placed in clean
      cages. These cardiovascular and behavioral responses lasted for 45 to 60 min.
      Those animals not moved to clean cages but present in the animal room when this
      procedure was done did not show significant increases in blood pressure, heart
      rate, or activity. When rats were moved to clean cages that contained new bedding
      plus a small quantity of the soiled bedding from their previous cage, the
      cardiovascular and behavioral responses were similar to those of animals exposed
      to completely fresh bedding. The responses of rats being moved to new cages did
      not diminish between the first and fourth weekly cage change. Rats whose cages
      were not changed for 2 weeks showed small, but significant, increases in
      cardiovascular and behavioral responses above the responses in animals with
      weekly cage changes. We conclude that ordinary animal husbandry procedures such
      as moving rats to a clean cage can induce transient, but significant,
      cardiovascular and behavioral changes. Investigators and animal care staff should
      recognize that such routine procedures could confound experiments conducted
      shortly thereafter.

PMID- 11300671
TI  - A comparison of two opioid analgesics for relief of visceral pain induced by
      intestinal resection in rats.
AB  - While developing a rat model for human short bowel syndrome, we noted that
      untreated rats as well as rats administered buprenorphine after intestinal
      resection exhibited behavior and appearance consistent with visceral pain and
      distress. To provide appropriate analgesics, we developed criteria to assess pain
      related behavioral changes and conducted an experiment to evaluate the
      effectiveness of buprenorphine versus oxymorphone to alleviate the pain induced
      by intestinal resection. Rats underwent either small-bowel resection or
      transection surgery; in addition, animals received jugular catheterization for
      the delivery of total parenteral nutrition (TPN). Rats treated with buprenorphine
      received 0.5 mg/kg every 6 h subcutaneously, and rats treated with oxymorphone
      received 0.03 mg/kg hourly for 32 h via continuous intravenous (i.v.) infusion
      with TPN solution. Rats treated with buprenorphine exhibited behavior and
      appearance consistent with pain and distress for as long as 32 h postoperatively,
      whereas animals treated with oxymorphone exhibited behavior and appearance
      similar to their preoperative state. Thus, oxymorphone alleviated the pain
      related behavioral changes after intestinal resection far better than did
      buprenorphine. Of interest, we observed that the buprenorphine was associated
      with a decrease in the volume of urine collected, whereas oxymorphone was
      associated with urine volumes similar to those of nonresected rats maintained
      with TPN. Because oxymorphone appeared to be a superior analgesic, we also
      evaluated three routes for administering this drug. Pain-related behavior changes
      were alleviated by the administration of oxymorphone by either Alzet mini-pump,
      bolus i.v. injection, or continuous i.v. infusion. We conclude that compared with
      buprenorphine, oxymorphone is a superior analgesic for the alleviation of
      visceral pain due to intestinal resection.

PMID- 11300672
TI  - Evaluation of objects and food for environmental enrichment of NZW rabbits.
AB  - The Guide for the Care and Use of Laboratory Animals states that both structural
      and social environments should be considered when addressing the husbandry needs
      of laboratory animals. The purpose of this study was to investigate environmental
      enrichment strategies that could potentially enhance the well-being of rabbits.
      Male and female 6-week old New Zealand White rabbits were divided into three
      groups: food-enriched (Bunny Stix, Bunny Blocks, or celery), non-food enriched
      (Jingle Ball, Kong toy, or Nylabone), and not enriched. Animals were given a
      particular enrichment for 1 h daily for 15 days. Home cages were fitted with
      specially designed plexiglass doors, which allowed the animals' interactions with
      the objects to be videotaped. The amount of time the animal interacted with each
      object and the total activity during the 1-h taped session were recorded for each
      rabbit. Rabbits were weighed weekly. Rabbits spent significantly more time
      interacting with the Bunny Stix than any other food item or non-food object. In
      addition, total activity time was significantly greater for all rabbits enriched
      with food versus any of the non-food items. Weight gains after 15 days did not
      differ significantly, but there was a trend towards increased weight gains in
      food-enriched rabbits. In this study, food was a stronger, more sustained
      enrichment device than were non-food objects.

PMID- 11300673
TI  - Enrichment-toy trauma in a New Zealand White rabbit.
AB  - An injury was caused by an enrichment toy (a whiffle ball, which is a perforated
      hollow ball made of hard plastic) that led to its removal from the rabbit
      enrichment program. Manipulata and food treats form the basis of the Yale rabbit
      enrichment program. All singly housed rabbits are given toys such as balls,
      chains, wood blocks, PVC tubing, Nylabones, and corrugated plastic tunnels.
      Before they are used, all potential enrichment devices are reviewed for safety
      and potential veterinary problems. The whiffle ball had been considered safe
      because it was made of hard non-toxic plastic, had no sharp edges, was too large
      to be swallowed or inhaled, and was judged too sturdy to be broken by the
      rabbits. However, the ball became lodged in the incisors of an adult female New
      Zealand White rabbit, preventing her from eating or drinking for 12 h and causing
      marked trauma to her gums. Removal of the ball necessitated anesthetizing the
      rabbit and using bone cutters to cut away the ball. Ideally, environmental
      enrichment should increase species-specific normal behavior and minimize
      stereotypies and self- and conspecific-directed abusive behavior. This case
      illustrates that safety assessments for an enrichment device must include both
      the inherent properties of the device and the risks if the toy is misused or
      damaged. Considerations for safety assessment are discussed.

PMID- 11300675
TI  - Restoration of fertility by transplantation of mouse ovary obtained postmortem.
AB  - During the course of breeding mice, deaths sometimes occur because of sudden
      onset disease or accident. In the case of valuable mutant or transgenic mice, it
      is of interest to know whether ovarian tissue taken after death can be grafted
      successfully into ovariectomized female recipients. Such a procedure would be
      helpful in the maintenance of rare mouse strains. In this study, we examined
      whether recipient mice became fertile after receiving ovaries taken from
      transgenic mice at various intervals after death. The transgenic mice used as
      donors were euthanized by cervical dislocation and left for 1, 2, 4, 6, 12, or 24
      h after death at constant temperature (22 +/- 2 degrees C) and humidity (55 +/-
      5%). The recipient mice were nontransgenic littermates of the donor mice, and
      they were mated with proven-fertile males after ovary transplantation. It was
      confirmed that the progeny carried the transgene by means of polymerase chain
      reaction analysis. Ovaries taken at 1 or 2 h after death could maintain
      fertility. However, mice receiving ovaries taken at 4, 6, 12, or 24 h after death
      failed to conceive. We have shown here that ovaries taken from dead mice within 2
      h after death can be transplanted successfully.

PMID- 11300674
TI  - Iatrogenic Horner's syndrome in an experimental pig.
AB  - An adult domestic female pig (Sus scrofa) exhibited clinical signs of right-sided
      Horner's syndrome after experimental placement of a woven aortic stent followed
      by aortic catheterization. The clinical signs included a miotic pupil, ptosis of
      the upper eyelid, prolapse of the nictitating membrane, and enophthalmos.
      Necropsy revealed a large mass in the right midcervical region that encased or
      was in contact with the carotid artery, internal jugular vein, and vagus nerve.
      Closer evaluation of the mass revealed that it was a small piece of surgical
      suture material that was embedded within the lumen of the carotid artery. This
      extrinsic material served as a nidus for an inflammatory reaction involving the
      vagus nerve.

PMID- 11300676
TI  - Elevated glycemia and local inflammation after injecting N-methyl-2-pyrrolidone
      (NMP) into the marginal ear vein of rabbits.
AB  - The objective of this pilot study was to evaluate glycemia in rabbits by
      administering various vehicles for solubilizing poorly soluble candidate drugs
      used for the treatment of diabetes. Groups of three New Zealand White rabbits
      received intravenously: saline; 2.0 IU/kg insulin; 23 to 45% dimethyl acetamide
      (DMA)/10% cremophor (v:v) in water; or N-methyl-2-pyrrolidone (NMP). For the
      determination of glycemia, blood was collected just before and 0.25, 0.5, 1, 2,
      4, and 24 h after injection. Glycemia after saline and DMA/cremophor injections
      remained stable and within the normal range (3.6 to 5.0 mmol/l). In insulin
      injected rabbits, glycemia decreased (1 to 2 mmol/l) as expected. With NMP,
      glycemia was elevated (7.8 mmol/l), and animals were hyperactive upon injections.
      Injected ears gradually became bluish; 48 h after injection, they were edematous
      and necrotic. In conclusion, DMA/cremophor seems to be an acceptable vehicle.
      However, NMP may cause stress and local ear irritation when injected
      intravenously in rabbits.

PMID- 11300677
TI  - Hepatocystosis in a baboon (Papio anubis).
AB  - A 26-lb wild-caught adult female baboon was obtained from a commercial vendor.
      Routine tests for parasites, pathogenic bacteria, and tuberculosis were negative
      throughout the 10-week quarantine. However, routine radiographs performed at the
      end of the quarantine period detected multiple small radioopaque nodules evenly
      dispersed throughout the liver. A hepatic biopsy was obtained during routine
      ovariectomy of the baboon, and a diagnosis of granulomatous hepatitis made.
      Approximately 1 year after her arrival, the baboon was euthanized for reasons
      unrelated to the hepatitis. The liver contained multiple (40 to 50) white foci
      that were 1 to 3 mm in diameter; these foci were visible on the surface as well
      as throughout the parenchyma. There was multifocal, moderate capsular fibrosis,
      with adhesions between the hepatic lobes and between the diaphragm and liver.
      Histologic examination revealed multiple degenerate Hepatocystis sp. merocysts.
      H. kochi and H. simiae are malarial-type nonpathogenic protozoa endemic to Old
      World nonhuman primates, including baboons. Infected animals are asymptomatic and
      do not experience hemolysis. Transmission requires an insect vector, therefore
      infection with Hepatocystis sp. has minimal implications for colony health. There
      is no known danger of transmission to humans.

PMID- 11300678
TI  - Unusual immunophenotype of a soft tissue sarcoma in a European polecat (Mustela
      putorius).
AB  - The most commonly reported tumors in ferrets are carcinomas, followed by round
      cell tumors. Soft tissue sarcomas are reported and characterized much less
      frequently. Because domesticated ferrets (Mustela putorius furo) are direct
      descendants of European polecats (Mustela putorius), the types and prevalence of
      tumors are expected to be similar in the two species. Presented here is a case
      report of unusual immunohistochemical staining characteristics of an abdominal
      wall leiomyosarcoma in a close relative of domestic ferrets, the European
      polecat. Sections of tissue were preserved in 10% buffered formalin, embedded in
      paraffin, and sectioned at 5 mm. Routine staining with hematoxylin and eosin and
      several immunohistochemical tests were performed to identify the tumor tissue of
      origin. Although the tumor did not stain with antibody to desmin, further
      staining for smooth muscle actin was consistent with a smooth muscle origin. To
      the authors' knowledge, this report is the first description of a leiomyosarcoma
      in the European polecat. This report emphasizes the importance of using
      additional secondary markers to accurately diagnose anaplastic tumors.

PMID- 11300679
TI  - Ribonuclease protection assay.

PMID- 11300680
TI  - The effect of brief halothane anesthesia during daily gavage on complications and
      body weight in rats.
AB  - We examined retrospectively the effects of brief halothane anesthesia during
      daily gavage administration of vehicle on gavage-related complications and body
      weight in ovariectomized female Wistar rats. The number of gavage-related deaths
      or animals requiring euthanasia due to gavage problems was dramatically reduced,
      but the occurrence of incomplete vehicle retention during gavage was increased
      appreciably in halothane-anesthetized animals. Halothane-anesthetized rats
      maintained daily body weight for a longer period than did awake animals. Our
      observations suggest that the use of brief inhalational anesthesia reduces gavage
      associated death and euthanasia due to esophageal trauma and minimizes stress
      related weight loss.

PMID- 11300681
TI  - Standardization of the Whitten Effect to induce susceptibility to Neisseria
      gonorrhoeae in female mice.
AB  - Female mice (Mus musculus) frequently are used to study hormonally related
      differences in susceptibility to infectious organisms or response to
      pharmaceutical agents. Cyclical variation in hormone levels within a group of
      mice, however, challenges the experimental design of such studies in that it is
      often difficult to obtain sufficient numbers of mice in the desired phase of the
      estrous cycle at the time of treatment. The purpose of this work is to provide
      investigators with a standardized protocol for inducing estrus in mice through
      exposure to male urine (Whitten Effect). In addition, we demonstrate how the
      Whitten Effect can be used to induce susceptibility of mice to Neisseria
      gonorrhoeae infection. Female BALB/c mice were exposed to male urine via soiled
      bedding for 0, 24, 48, 72, or 96 h. The effect of exposure on the reproductive
      cycle was monitored by cytologic examination of vaginal smears and measurement of
      serum 17-b estradiol levels by using a nonradioactive immunoassay kit. In a
      separate experiment, mice were exposed to male-urine-soaked bedding for 0, 24,
      72, or 96 h prior to intravaginal inoculation with Neisseria gonorrhoeae.
      Infection was monitored by using vaginal culture for 5 consecutive days. We found
      that the highest percentage of mice in estrus occurred among mice that were
      exposed to male-urine-soaked bedding for 96 h. Consistent with this finding was
      the demonstration that mice were more susceptible to gonococcal infection after
      exposure to male urine for 3 to 4 days. We conclude that exploitation of this
      natural murine behavioral response is a simple and inexpensive method by which
      estrus can be synchronized in a group of mice within a defined period of time. In
      addition, this protocol can be used to increase mouse susceptibility to
      experimental gonococcal infection.

PMID- 11300682
TI  - Suspected hypovitaminosis A in a colony of captive green anoles (Anolis
      carolinensis).
AB  - In a colony of 18 green anoles (Anolis carolinensis), 3 animals experienced
      focally thickened lips, ulcerative cheilitis, lethargy, depression, and weight
      loss over a 5-month period. In addition to crickets fed fresh fruit and leafy
      green vegetables, the diet of the green anoles consisted of a supply of mealworms
      that had been dusted with a commercial liquid vitamin supplement. The history,
      clinical findings, and histopathologic lesions were suggestive of hypovitaminosis
      A, which is known to cause squamous metaplasia of the mucus secreting glands and
      epithelial surfaces in many species.

PMID- 11300683
TI  - Helminth fauna of the golden hamster Mesocricetus auratus in Brazil.
AB  - Helminth fauna of conventionally maintained hamsters from institutional animal
      houses that supply the research community with laboratory animals and from an
      openly kept control group, randomly purchased in a pet shop in the State of Rio
      de Janeiro, were evaluated and compared. Necropsied animals from institutional
      suppliers were infected with the oxyurid nematodes Syphacia criceti and S.
      mesocriceti and with the cestode Rodentolepis nana; those from the pet shop were
      infected with S. mesocriceti and R. nana. These are the first morphometric data
      that are based on Brazilian samples of these species parasitizing hamsters.
      Mesocricetus auratus is a newly recorded host for S. criceti, previously
      recovered from Oryzomys subflavus and Calomys callosus in Brazil. The potential
      of pet and laboratory hamsters in the spreading of helminth infections to humans
      is also considered.

PMID- 11300684
TI  - A simplified method to prepare PCR template DNA for screening of transgenic and
      knockout mice.
AB  - Polymerase chain reaction (PCR) amplification of DNA is the most widely used
      technique for screening of large numbers of genetically engineered transgenic or
      knockout mice (Mus musculus). In this report, we present a new DNA preparation
      procedure for running diagnostic PCR. In this procedure, mouse ear tissue was
      used directly for PCR after the tissue underwent brief digestion in a solution
      containing only proteinase K. Using this method, we have successfully screened
      several lines of single, double, and triple transgenic and knockout mice. The
      results are reliable and reproducible. The advantage of this new method is that
      DNA purification by organic extraction or isolation kit was omitted. DNA
      purification is the limiting factor in terms of time and money when screening
      transgenic and knockout mice by PCR. In addition, using ear instead of tail
      tissue can reduce distress of animals because the samples can be obtained when
      the mice are labeled by ear punch.

PMID- 11300685
TI  - Application of the piezo-micromanipulator for injection of embryonic stem cells
      into mouse blastocysts.
AB  - Microinjection of embryonic stem (ES) cells into mouse blastocysts is one of the
      most important techniques for production of knockout or transgenic mice. However,
      skillful manipulation techniques and tremendous effort are required for this
      method. To overcome this difficulty, we applied a piezo-micromanipulator (PMM),
      which has been used for intracytoplasmic sperm injection in mice and production
      of cloned mice, for the injection of ES cells into blastocysts. When ES cells
      were injected by using a conventional method, 91% of the blastocysts were
      manipulated successfully. Using the PMM significantly (P < 0.01) increased the
      success rate of ES injection to 97%. The number of embryos manipulated in an hour
      increased from 9.7 embryos with the conventional method to 27.0 embryos with the
      PMM method. The injected ES cells did not show any detrimental effects due to a
      pulse from the PMM. After embryo transfer of the manipulated blastocysts, 39% of
      the newborns were chimeric mice with the conventional method, whereas 42% of the
      neonates were chimeric after the PMM method. These results indicate that
      microinjection of the ES cells into blastocysts is more efficient by the PMM
      method than the conventional method.

PMID- 11300686
TI  - A topical mixture for preventing, abolishing, and treating autophagia and self
      mutilation in laboratory rats.
AB  - The dysesthesia and paresthesia that occurs in laboratory rats after spinal cord
      injury and peripheral nerve injury results in autophagia and self-mutilation.
      This self-destructive behavior interferes with functional assessments in designed
      studies and jeopardizes the health of the injured rat. We developed a topical
      mixture that prevents, abolishes, and treats autophagia and self-mutilation. When
      the mixture is applied to the limb, its bitterness effectively prevents the rat
      from licking and biting the limb. In addition, the mixture has antiseptic
      properties.

PMID- 11300687
TI  - Nonendoscopic placement and use of percutaneous gastrostomy tubes in pigs (Sus
      scrofa domestica).
AB  - Swine have supplanted dogs and other large animal species in many biomedical
      applications and have become the model of choice for numerous areas of research.
      Anatomic, behavioral, and handling concerns often require pigs to be surgically
      instrumented for many procedures. Oral dosing in pigs can be accomplished by
      feeding substances in a palatable substrate, temporarily placing an oral or nasal
      gastric tube, or permanent surgical placement of an esophagostomy or gastrostomy
      tube. Oral and nasal gastric tube placement is difficult in conscious,
      unrestrained animals and is suitable only for short-term enteral access. Placing
      esophagostomy and gastrostomy tubes is suitable for long-term enteral access and
      allows easy and rapid administration of substances directly into the stomach.
      However, these methods frequently require major surgical manipulation for
      placement. Nonendoscopic percutaneous gastrostomy tube placement is used in
      companion animals to establish permanent or temporary enteral access. We
      successfully have adapted this procedure in swine as a method for short-term
      enteral access. This technique has several advantages over the traditional
      surgical method for gastrostomy tube placement. It is minimally invasive, results
      in less animal pain and distress, requires less procedural and recovery time, and
      is inexpensive. Disadvantages include the potential for splenic entrapment,
      splenic penetration, perforation of the esophagus, and other complications
      related to misplacement of the tube or applicator. This paper describes the
      equipment, technique, and potential complications for placing a nonendoscopic
      percutaneous gastrostomy tube in swine.

PMID- 11300688
TI  - Design and use of a protective jacket to prevent self-inflicted injury following
      cervical laminoplasty in the goat (Capra hircus).
AB  - A group of dairy goats underwent cervical laminoplasty procedures as part of a
      biomechanics project. Although most animals had minimal incisional complications,
      several developed excoriations exacerbated by scratching at the incision site 6
      to 8 weeks after the surgery. Local and systemic treatment was instituted as
      indicated. Bandages were inadequate to protect the neck from self-trauma, and the
      potential existed for serious injury to or infection of the old surgical site. We
      designed and made custom padded jackets for these animals. Treatment continued.
      While allowing the animals to exercise their scratching behavior, the jackets
      protected the traumatized area until healing was complete and the pruritus
      resolved. This jacket or modifications of it may be useful in other goat, sheep,
      or calf projects in which protection of the neck, shoulders, and thorax is
      needed.

PMID- 11300689
TI  - Cysticercosis in laboratory rabbits.
AB  - There are no data on the current incidence of Taenia pisiformis in laboratory
      rabbits. Two cases of cysticercosis most likely due to T. pisiformis in
      laboratory rabbits (intermediate host) are presented. Both rabbits had no contact
      with dogs (final host); their caretakers did not work with dogs, and these
      caretakers changed into facility scrubs and wore gloves when working with the
      rabbits. Rabbit 1 may have been infected after being fed hay at our facility. In
      light of the life cycle of the parasite and the history of rabbit 2, it
      potentially could have been infected prior to arrival at our facility. There have
      been only three cases of tapeworm cysts in rabbits in our facility (average daily
      census, 250) during the last 10 years (incidence, < 1%). This report indicates
      that although cysticercosis is rare in laboratory rabbits, one should always be
      aware of such incidental findings. Although it may not produce overt illness in
      the rabbit, hepatic migration could adversely affect the outcome of some
      experimental procedures

PMID- 11300690
TI  - The multiple functions of coenzyme Q.
AB  - The coenzyme function of ubiquinone was subject of extensive studies in
      mitochondria since more than 40 years. The catalytic activity of ubiquinone (UQ)
      in electron transfer and proton translocation in cooperation with mitochondrial
      dehydrogenases and cytochromes contributes essentially to the bioenergetic
      activity of ATP synthesis. In the past two decades UQ was recognized to exert
      activities which differ from coenzyme functions in mitochondria. From
      extraction/reincorporation experiments B. Chance has drawn the conclusion that
      redox-cycling of mitochondrial ubiquinone supplies electrons for univalent
      reduction of dioxygen. The likelihood of O2(.-) release as normal byproduct of
      respiration was based on the existence of mitochondrial SOD and the fact that
      mitochondrial oxygen turnover accounts for more than 90% of total cellular oxygen
      consumption. Arguments disproving this concept are based on results obtained from
      a novel noninvasive, more sensitive detection method of activated oxygen species
      and novel experimental approaches, which threw light into the underlying
      mechanism of UQ-mediated oxygen activation. Single electrons for O2(.-) formation
      are exclusively provided by deprotonated ubisemiquinones. Impediment of redox
      interaction with the bc1 complex in mitochondria or the lack of stabilizing
      interactions with redox-partners are promotors of autoxidation. The latter
      accounts for autoxidation of antioxidant-derived ubisemiquinones in biomembranes,
      which do not recycle oxidized ubiquinols. Also O2(.-)-derived H2O2 was found to
      interact with ubisemiquinones both in mitochondria and nonrecycling biomembranes
      when ubiquinol was active as antioxidant. The catalysis of reductive homolytic
      cleavage of H2O2, which contributes to HO. formation in biological systems was
      confirmed under defined chemical conditions in a homogenous reduction system.
      Apart from dioxygen and hydrogen peroxide we will provide evidence that also
      nitrite may chemically interact with the ubiquinol/bc1 redox couple in
      mitochondria. The reaction product NO was reported elsewhere to be a significant
      bioregulator of the mitochondrial respiration and O2 activation. Another novel
      finding documents the bioenergetic role of UQ in lysosomal proton intransport. A
      lysosomal chain of redox couples will be presented, which includes UQ and which
      requires oxygen as the terminal electron acceptor.

PMID- 11300691
TI  - Stereoselective reduction with NADH model BNAH through chiral induction in
      cyclodextrins.
AB  - Stereoselective reductive debromination-cyclopropanation of 2-bromo-1
      phenylethylidene-malononitrile and 2-bromo-1-beta-naphthylethylidenemalononitrile
      by coenzyme NADH model BNAH through chiral induction in cyclodextrins is
      reported. The matching between substrates and cyclodextrins, the substituent
      effect, and the effect of cyclodextrin concentration on the optical yields have
      been investigated.

PMID- 11300692
TI  - Fluorometric studies on inclusion complexation of L/D-tryptophan by beta
      cyclodextrin 6-O-pyridinecarboxylates.
AB  - Novel beta-cyclodextrin (beta-CD) derivatives, bearing a nicotinic or
      isonicotinic moiety, have been synthesized by a convenient method in 21 and 25%
      yields, respectively. The stability constants (K) and Gibbs free energy changes (
      DeltaG degrees ) for the inclusion complexation of beta-cyclodextrin 6-O-mono(3
      pyridinecarboxylate) (1), 6-O-mono(4-pyridinecarboxylate) (2), and 6-O
      monobenzoate (3) with L- and D-tryptophan have been determined by spectrofluorome
      try in aqueous buffer solution (pH = 7.20) at 25.0 degrees C. All of the
      modifications dramatically enhanced the original K for beta-CD by a factor of 30
      280 and interestingly switched the original enantiomer preference for L- to D
      tryptophan, thus affording the inverted enantio-selectivities of K(L)/K(D) = 2.5
      for beta-CD and K(D)/K(L) = 1.2-2.1 for the modified CDs 1-3. These results are
      discussed from the viewpoints of the size-fit and geometrical complementary
      relationship between the host and guest.

PMID- 11300693
TI  - Stereochemical specificity of organophosphorus acid anhydrolase toward p
      nitrophenyl analogs of soman and sarin.
AB  - Organophosphorus acid anhydrolase (OPAA) catalyzes the hydrolysis of p
      nitrophenyl analogs of the organophosphonate nerve agents, sarin and soman. The
      enzyme is stereoselective toward the chiral phosphorus center by displaying a
      preference for the R(P)-configuration of these analogs. OPAA also exhibits an
      additional preference for the stereochemical configuration at the chiral carbon
      center of the soman analog. The preferred configuration of the chiral carbon
      center is dependent upon the configuration at the phosphorus center. The enzyme
      displays a two- to four-fold preference for the R(P)-enantiomer of the sarin
      analog. The k(cat)/K(m) of the R(P)-enantiomer is 250 M(-1) s(-1), while that of
      the S(P)-enantiomer is 110 M(-1) s(-1). The order of preference for the
      stereoisomers of the soman analog is R(P)S(C) > R(P)R(C) > S(P)R(C) > S(P)S(C).
      The k(cat)/K(m) values are 36,300 M(-1)s(-1), 1250 M(-1) s(-1), 80 M(-1) s(-1)
      and 5 M(-1) s(-1), respectively. The R(P)S(C)-isomer of the soman analog is
      therefore preferred by a factor of 7000 over the S(P)S(C)-isomer.

PMID- 11300695
TI  - Bioactive four-membered heterocyclic compounds: the anti --> syn interconversion
      in dithietane-1,3-dioxide.
AB  - The anti-dithietane-1,3-dioxide --> syn-dithietane-1,3-dioxide isomerization
      reaction has been theoretically studied on the frame of MO theory both in the gas
      phase and in solution. In the gas phase the anti (II(a)) <--> syn (II(s))
      equilibrium is slightly displaced to the anti isomer formation. The syn
      concentration ([Syn]) is ca. 36% in the gas phase, whereas in low polarity
      solvent, such as carbon tetrachloride, [Syn] is ca. 63%. In medium-high polarity
      solvents like acetonitrile and dimethyl-sulfoxide the [ anti]/[ syn ] ratio is
      ca. 0.37.

PMID- 11300694
TI  - Inhibition of human telomerase by 7-deaza-2'-deoxyguanosine nucleoside
      triphosphate analogs: potent inhibition by 6-thio-7-deaza-2'-deoxyguanosine 5'
      triphosphate.
AB  - We have examined analogs of the previously reported 7-deaza-2'-deoxypurine
      nucleoside triphosphate series of human telomerase inhibitors. Two new telomerase
      inhibiting nucleotides are reported: 6-methoxy-7-deaza-2'-deoxyguanosine 5'
      triphosphate (OMDG-TP) and 6-thio-7-deaza-2'-deoxyguanosine 5'-triphosphate (TDG
      TP). In particular, TDG-TP is a very potent inhibitor of human telomerase with an
      IC(50) of 60 nM. TDG-TP can substitute for dGTP as a substrate for telomerase,
      but only at relatively high concentrations. Under conditions in which TDG-TP is
      the only available guanosine substrate, telomerase becomes nonprocessive,
      synthesizing short products that appear to contain only one to three TDG
      residues. Similarly, the less potent telomerase inhibitor OMDG-TP gives rise to
      short telomerase products, but less efficiently than TDG-TP. We show here that
      TDG-TP, and to a lesser extent OMDG-TP, can serve as substrates for both
      templated (Klenow exo) and nontemplated (terminal transferase) DNA polymerases.
      For either polymerase, the products arising from TDG-TP are relatively short, and
      give rise to bands of unusual mobility under PAGE conditions. These anomalous
      bands revert, under treatment with DTT, to normal mobility bands, indicating that
      these products may contain thiol-labile disulfide linkages involving the
      incorporated TDG residues. This observation of potential TDG-crosslinks may have
      bearing on the mechanism of telomerase inhibition by this nucleotide analog.

PMID- 11300696
TI  - Effects of substituent and temperature on enantioselectivity for lipase-catalyzed
      esterification of 2-(4-substituted phenoxy) propionic acids in organic solvents.
AB  - Substituent effects on the enantioselectivity for the lipase-catalyzed
      esterifications in organic solvents were studied by use of 2-(4-substituted
      phenoxy)propionic acids as the substrates with various substituents of H, F, Cl,
      CF(3), CH(3), CH(3)CH(2), and CH(3)O. The distinction in the behavior of their
      enantioselectivity was primarily responsible for the size effects of the
      substituents, although the substituents are far away from the stereocenter of the
      substrates. For the similar substituents in size, CH(3) and CF(3), however, their
      electronic effects played an important role in controlling the
      enantioselectivity. This variation of the enantioselectivity due to the
      electronic effects is also supported by the discussion based on the value of the
      Michaelis constant (K(m)) obtained. In addition, by raising the reaction
      temperature with enough water added to isopropyl ether as the reaction medium,
      the enantioselectivity is found to be dramatically enhanced for the substrate
      bearing CH(3)O group due to the strong electron-donating effect.

PMID- 11300697
TI  - The relative catalytic efficiency of beta-lactamase catalyzed acyl and phosphyl
      transfer.
AB  - Phosphonamidates which bear a simple resemblance to penicillin type structures
      have been synthesised as potential inhibitors of beta-lactamases: -ethyl N
      (benzyloxycarbonyl) amidomethyl phosphonyl amides,
      PhCH(2)OCONHCH(2)P(O)(OEt)NR(2), the amines HNR(2) being l-proline, d-proline, l
      thiazolidine, and o-anthranilic acid. The proline derivatives completely and
      irreversibly inactivated the class C beta-lactamase from Enterobacter cloacae
      P99, in a time-dependent manner, indicative of covalent inhibition. The
      inactivation was found to be exclusive to the class C enzyme and no significant
      inhibition was observed with any other class of beta-lactamase. The anthranilic
      acid derivative exhibited no appreciable inactivation of the beta-lactamases. The
      phosphonyl proline and phosphonyl thioproline derivatives were separated into
      their diastereoisomers and their individual second order rate constants for
      inhibition were found to be 7.72 +/- 0.37 and 8.3 x 10(-2) +/- 0.004 M(-1) s(-1)
      for the l-proline derivatives, at pH 7.0. The products of the inhibition reaction
      of each individual diastereoisomer, analyzed by electrospray mass spectroscopy,
      indicate that the more reactive diastereoisomers phosphonylate the enzyme by P-N
      bond fission with the elimination of proline. Conversely, gas chromatographic
      detection of ethanol release by the less reactive proline diastereoisomer
      suggests phosphonylation occurs by P-O bond fission. The enzyme enhances the rate
      of phosphonylation with P-N fission by at least 10(6) compared with that effected
      by hydroxide-ion. The pH dependence of the rate of inhibition of the beta
      lactamase by the more reactive diasteroisomer is consistent with the reaction of
      the diprotonated form of the enzyme, EH(2), with the inhibitor, I (or its kinetic
      equivalents EH with IH). This pH dependence and the rate enhancement indicate
      that the enzyme appears to use the same catalytic apparatus for phosphonylation
      as that used for hydrolysis of beta-lactams. The stereochemical consequences of
      nucleophilic displacement at the phosphonyl centre are discussed.

PMID- 11300698
TI  - A reexamination of the substrate utilization of 2-thioorotidine-5'-monophosphate
      by yeast orotidine-5'-monophosphate decarboxylase.
AB  - A potential alternate substrate for orotidine-5'-monophosphate decarboxylase, 2-
      thio-orotidine-5'-monophosphate, was synthesized enzymatically and purified by a
      modification of a previous account (K. Shostak, and M. E. Jones 1992,
      Biochemistry 31, 12155-12161). Characterization of the product was confirmed by
      mass spectrometry, (31)P NMR, and utilization by orotate
      phosphoribosyltransferase in the direction of pyrophosphorolysis. The previous
      work probably did not result in the purification of the desired compound, as
      evidenced by our observation of 2-thioOMP's sensitivity to high temperature, as
      used previously. Using a very sensitive HPLC assay for the potential
      decarboxylated product 2-thioUMP, no measurable activity of ODCase toward the
      alternate substrate was observed, representing a decarboxylation rate decreased
      by 10(-7) from the k(cat) for ODCase toward OMP. Additionally, 2-thioOMP effects
      no inhibition of ODCase decarboxylation of OMP at a concentration of 50 microM,
      indicating a poor ability to bind to the ODCase active site. The results bear
      implications for proposed mechanisms for catalysis by ODCase.

PMID- 11300699
TI  - Targeting telomerase via its key RNA/DNA heteroduplex.
AB  - Telomerase is a promising "universal" anticancer target. It has been demonstrated
      that inhibition of telomerase leads to mortalization and death of previously
      immortal cell lines. We are interested in targeting telomerase by binding to the
      RNA/DNA duplex that forms during its catalytic cycle. The RNA strand of this
      duplex is a component of telomerase and acts as a template to direct the
      synthesis of the single-stranded DNA telomere. We have hypothesized that
      molecules that bind to this duplex will inhibit the enzyme by either preventing
      strand dissociation or by sufficiently distorting the substrate, thereby causing
      a misalignment of key catalytic residues. To test this hypothesis we have
      examined the activity of telomerase in the presence of a range of intercalating
      molecules, known for their broad duplex binding properties. Of the nine compounds
      we examined, four show promising lead activity in the low micromolar range. A
      kinetic analysis of the telomeric products suggests that these compounds do not
      act by stabilizing G-quartets, thereby supporting the telomeric RNA/DNA
      heteroduplex as the site of action. We anticipate using these lead compounds as
      the basis for combinatorial variation to increase the affinity and specificity
      for the target telomerase.

PMID- 11300700
TI  - Cerebral laterality for famous proper nouns: visual recognition by normal
      subjects.
AB  - Lexical processing has long been associated with left-hemisphere function,
      especially for infrequently occurring words. Recently, however, persons with
      severe aphasia, including word-recognition deficits, were observed to recognize
      familiar proper nouns. Further, some patients suffering right-hemisphere damage
      were poorer at identifying famous names than left-hemisphere-damaged subjects.
      These observations point to the possibility that some property of the right
      hemisphere provides an advantage for the processing of familiar or personally
      relevant stimuli. To investigate this possibility, we conducted split-visual
      field studies in which we manipulated stimulus sets, recognition task, and
      exposure duration. Greater accuracy in the right visual field was found for
      common nouns and unknown proper nouns, and famous proper nouns were overall more
      accurately recognized. Performance for famous nouns in the two visual fields was
      not significantly different when the task required categorization into famous or
      nonfamous and when stimuli most highly rated as familiar were used. These
      findings support our proposals that (1) both hemispheres can process famous
      proper nouns and (2) the right hemisphere is specialized for personal relevance.

PMID- 11300701
TI  - Two different dysgraphic syndromes in a regular orthography, spanish.
AB  - In opaque orthographies, such as English and French, three central dysgraphic
      syndromes have been described: surface dysgraphia, phonological dysgraphia, and
      deep dysgraphia. Writing breakdown patterns reveal that spelling can proceed by
      phoneme-to-grapheme conversion, or by a more direct or lexical approach. Ardila
      et al. (1989, 1991) claim that for Spanish speakers a lexical strategy for
      reading and writing is not an option due to the regularity of the orthography of
      this language. In this study we report two clear cases of dysgraphia in Spanish,
      one of surface dysgraphia and another of phonological dysgraphia, where a
      dissociation between lexical and sublexical writing can be observed, thus
      contradicting Ardila's position.

PMID- 11300702
TI  - Are semantic errors actually semantic?: Evidence from alzheimer's disease.
AB  - Patients with Alzheimer's disease (AD) produce a high rate of semantic errors
      when naming to confrontation. This is considered to be one of the many
      consequences of their semantic memory deficit. However, it has been shown, in
      aphasic patients with focal lesions, that semantic errors could arise from
      impairment to any one of the levels in the naming process. To check this
      hypothesis in AD, we assessed in 15 patients the capacity to name and access
      semantic knowledge (by multiple-choice probe questions) about 14 objects
      presented successively in the visual, tactile, auditory, and verbal modalities.
      In the visual naming task, 33 errors were recorded: 26 (78.8%) were semantic and
      7 (21.2%) were unrelated errors. Of the 26 semantic errors, 8 were related to a
      deficit of the semantic knowledge related to the item and 17 to a deficit in the
      retrieval of the phonological form of the word. One was associated with a deficit
      of access to semantic knowledge in the visual modality. The 7 unrelated errors
      were associated with a loss of semantic knowledge for 4 and deficit of access to
      the phonological form for 3. In conclusion, this study shows that semantic errors
      do not systematically reflect a deficit of semantic knowledge in Alzheimer's
      disease. It also seems that unrelated errors are more frequently related to
      semantic deficits than semantic errors in this population.

PMID- 11300703
TI  - Wine descriptive language supports cognitive specificity of chemical senses.
AB  - In order to understand wine perception we analyzed tasting notes of four expert
      wine tasters. The analysis is based on co-occurrence calculations of words within
      the tasting notes using ALCESTE software. The results of such an analysis of one
      subject's notes give us word classes reflecting main text ideas and organization
      of the text. In the present paper we interpret these "results" as follows: (1)
      Class number and organization are different among experts so that each expert has
      his own discourse strategy. (2) Wine language is based on prototypes and not on
      detailed analytical description. (3) Prototypes include not only sensory but also
      idealistic and hedonistic information. These results are in agreement with recent
      neurophysiological data.

PMID- 11300704
TI  - Ethanol reduces rCFB activation of left dorsolateral prefrontal cortex during a
      verbal fluency task.
AB  - In a previous study in normal subjects (Wendt et al., 1994), using a reversing
      checkerboard as activation stimulus, we found that the coupling between local
      neuronal activity and regional cerebral blood flow was preserved following
      ethanol, and that a right-sided occipital activation response seen during
      sobriety became symmetrical during inebriation. In the present study we
      investigated if ethanol has a detrimental effect also on the activation of the
      left dorsolateral prefrontal cortex found in normals during verbal fluency.
      Measurements of regional cerebral blood flow in 20 healthy, young, male, right
      handed volunteers during rest and verbal fluency were made during sobriety and
      inebriation (0.06% blood alcohol concentration) with a 1-week interval. We found
      a decrease in word production during inebriation. The normal activation within
      the frontotemporal part of the left dorsolateral prefrontal cortext was preserved
      during inebriation. The activation of this region seems thus to be robust to the
      effects of ethanol. During inebriation no activation response to the word fluency
      test was found in the anterior prefrontal part of the dorsolateral prefrontal
      cortex. This region is important for working, temporal, and short-term memory
      functions, processes that are affected by ethanol. Hemispheric functioning and
      specialization seem to be adversely affected by ethanol, regardless of which
      hemisphere is most involved while sober.

PMID- 11300705
TI  - Communicative abilities in autism: evidence for attentional deficits.
AB  - Although there are many theories about autism, something all of them agree upon
      is that autistics are impaired in the ability to communicate. The explanation is
      either their incapacity to attribute mental states to others or the interference
      of irrelevant stimuli with the access and processing of the communication (low).
      Our study on mute autistic children aims to investigate their communicative
      ability in order to bring some new evidence on the debate. We used an
      experimental technique that allows autistic children to access and process the
      communicative acts in a familiar context for as long as needed. The experimental
      results show that our sample of autistic children performs as well as the control
      group of normal children in dealing with directs, indirects, ironies, deceits,
      and recoveries of failure. Independent of their respective difficulty, the
      felicitous outcome of any of these acts requires the capacity to attribute an
      adequate communicative intention to the actor. Moreover, our results show that,
      contrary to the established findings in the literature, autistics' performance in
      the standard false belief task, a task that requires one to understand the mental
      states of other people, is equivalent to the performance of normal subjects. We
      argue that an attentional deficit affects the communicative performance of
      autistics in experiments where classic methodologies are used; with the proper
      methodology, we can access the unexplored world where mute autistic children also
      communicate. As far as we know, this is the first systematic experiment on
      pragmatic abilities in mute autistic children. Indeed, our work shows that tests
      and methodologies which help to focus on the communicative task improve the
      autistics' performance with respect to those used in the literature. We conclude
      that the autistic communicative deficit is at the performance level and that it
      has an attentional nature.

PMID- 11300706
TI  - Phonologically related lexical repetition disorder: a case study.
AB  - Errors of repetition in aphasia are most often nonword substitutions.
      Phonologically related lexical errors, or formal errors, are real-word
      substitutions that overlap with target words in sound. In the present research we
      present the case of an aphasic patient, MMB, who produced an unusually high rate
      of formal paraphasias in repetition. Six experiments were conducted to
      investigate the combination of impairments contributing to MMB's pattern of
      repetition and to test the predictions made by two theories of formal errors.
      MMB's formal errors in repetition were influenced by target frequency, but not by
      target length or imageability. Formal errors tended to be more frequent than
      their targets and showed greatest phonological overlap with targets at initial
      consonant. These findings provided partial support for Martin and Saffran's fully
      interactive spreading activation account of formal errors and did not support
      Blanken's phonological interactive encoding account. In Experiment 6, the effect
      on repetition of increasing auditory verbal short-term memory (AVSTM) demands was
      examined using a paired word repetition experiment. Under these conditions, MMB
      produced semantic paraphasias for the first time, providing strong support for
      the Martin-Saffran hypothesis that phonologically related, and semantic, lexical
      repetition disorders lie on a continuum of severity moderated by the degree of
      AVSTM impairment.

PMID- 11300708
TI  - Changes in the secondary sexual adornments of male mandrills (Mandrillus sphinx)
      are associated with gain and loss of alpha status.
AB  - Two semifree-ranging mandrill groups, inhabiting large, naturally rainforested
      enclosures in Gabon, were studied to measure morphological, endocrine, and
      behavioral changes that occurred when adult males rose, or fell, in dominance
      rank. Gaining alpha rank (N = 4 males) resulted in increased testicular size and
      circulating testosterone, reddening of the sexual skin on the face and genitalia,
      and heightened secretion from the sternal cutaneous gland. Blue sexual skin
      coloration was unaffected. New alpha males increased in rump "fattedness," but
      not in body mass, and spent more time associated with other group members, rather
      than ranging alone. Loss of alpha position (N = 4 males) resulted in less
      pronounced effects than those that occurred after males had risen to alpha
      positions. Deposed alpha males showed decreased testicular volume, decreased body
      mass, a reduction in the extent of red (but not blue) sexual skin coloration, and
      decreased sternal gland activity. Deposed males did not decrease in the
      brightness of sex skin coloration. These results demonstrate that male-male
      competition and rank reversals have remarkable effects upon testicular function,
      secondary sexual traits, and behavior in the adult male mandrill. Secondary
      sexual traits respond to changes in male social status and therefore may be
      important as intrasexual signals of dominance rank.

PMID- 11300709
TI  - The influence of testosterone on territorial defence and parental behavior in
      male free-living rufous whistlers, Pachycephala rufiventris.
AB  - We studied a population of rufous whistlers, Pachycephala rufiventris, throughout
      a single breeding season in central New South Wales, Australia. We evaluated the
      relation between plasma testosterone (T) and reproductive behaviors using both
      simulated territorial intrusions (STIs) and subcutaneous T implants. We compared
      circulating T values to aggression levels of males (using STI) during pair bond
      and territory establishment and again during incubation. Although plasma T levels
      were significantly lower in the latter period, male responsiveness to STI, in
      terms of proximity to decoy, call rate, and number of attacks on the decoy, was
      indistinguishable between the two breeding stages. T levels of males exposed to
      STI were not different from the levels of unexposed free-living males at the same
      breeding stage. The effect of exogenous T on parental behavior was examined by
      comparing duration of incubation bouts of males and their mates prior to and
      after T treatment. T males significantly reduced the amount of time they
      incubated following implantation, whereas Control males maintained their
      incubation effort. After cessation of breeding activities, T males displayed
      significantly higher call rates due to increased use of the primary intersexual
      advertisement call in this species. The reduction of incubation behavior
      following T implantation emphasises the functional significance of the rapid
      decline in T in free-living males during incubation. The results from both
      experiments suggest that intersexual advertisement, rather than territorial
      aggression, may be dependent on high T levels in this species.

PMID- 11300710
TI  - Rapid changes in monoamine levels following administration of corticotropin
      releasing factor or corticosterone are localized in the dorsomedial hypothalamus.
AB  - Monoaminergic systems are important modulators of the neuroendocrine, autonomic,
      and behavioral responses to stress-related stimuli. The male roughskin newt
      (Taricha granulosa) was used as a model system to investigate the effects of
      corticotropin-releasing factor (CRF) or corticosterone administration on tissue
      concentrations of norepinephrine, epinephrine, dopamine, 3,4
      dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) in
      microdissected brain areas. Intracerebroventricular infusion of 25 or 50 ng of
      CRF increased locomotor activity and site-specifically increased dopamine
      concentrations within the dorsomedial hypothalamus 30 min after treatment when
      compared to vehicle-treated controls. In further studies, male newts were treated
      as follows: (1) no injection, no handling, (2) saline injection, or (3) 10 microg
      corticosterone and then placed in a novel environment. Monoamine and monoamine
      metabolite concentrations were similar in the unhandled and saline-injected
      controls 20 min after treatment. In contrast, corticosterone-injected newts had
      elevated concentrations of dopamine, serotonin, and 5-HIAA in the dorsomedial
      hypothalamus (a region that contains dopamine- and serotonin-accumulating
      neuronal cell bodies in representatives of all vertebrate classes) but not in
      several other regions studied. These site-specific neurochemical effects parallel
      neurochemical changes observed in the dorsomedial hypothalamic nucleus of mammals
      following exposure to a variety of physical and psychological stress-related
      stimuli. Therefore, these changes may reflect highly conserved, site-specific
      neurochemical responses to stress and stress-related neurochemicals in
      vertebrates. Given the important role of the dorsomedial hypothalamus in
      neuroendocrine, autonomic, and behavioral responses to stress, and a proposed
      role for this region in fast-feedback effects of glucocorticoids on the
      hypothalamo-pituitary-adrenal axis, these stress-related monoaminergic changes
      are likely to have important physiological or behavioral consequences.

PMID- 11300711
TI  - Effects of prostaglandin F2alpha treatment of pseudopregnant pigs on nest
      building and interactions with newborn piglets.
AB  - Previous studies showed that prostaglandin (PG)F2alpha treatment stimulated nest
      building behaviors in prepartum and pseudopregnant pigs. This experiment studied
      behaviors of PGF2alpha-treated pseudopregnant nulliparous pigs (gilts) exposed to
      newborn piglets. Penned pseudopregnant gilts (days 46-53) were injected with
      either 10 mg PGF2alpha (n = 8) or saline (n = 8) im, and behavior was recorded
      for 2 h (period A). Between 2 and 6 h (period B), gilts were given two male
      piglets (< 12 h old) and a novelty object (house brick) and recordings continued.
      During period A, PGF2alpha animals showed greater frequencies of standing,
      pawing, rooting, lifting, and carrying straw (indices of nest building) and
      scratching than saline treated animals. During period B, one PGF2alpha- and two
      saline-treated gilts attacked piglets, which were removed from the pen and the
      gilts excluded from further analysis. There were no treatment differences in
      period B in gilt posture, nest building behavior, or interactions with piglets or
      novelty object, except for a reduced frequency to trap piglets beneath their
      bodies and an increased frequency to attempt to escape from the pen in PGF2alpha
      treated animals. Piglet position relative to the gilts' head and udder was
      unaffected by treatment. Gilts in both groups approached and nosed piglets more
      within the first 30 min of period B than subsequently. PGF2alpha-induced nest
      building had only a weak impact upon subsequent interactions between gilts and
      piglets, suggesting that mechanisms controlling porcine nest building and
      maternal behavior in this model were not directly linked.

PMID- 11300712
TI  - Testosterone restoration of copulatory behavior correlates with medial preoptic
      dopamine release in castrated male rats.
AB  - The medial preoptic area (MPOA) is an important integrative site for male sexual
      behavior. We have reported an increase in dopamine (DA) release in the MPOA of
      male rats shortly before and during copulation. Postcastration loss of copulatory
      ability mirrored the loss of the precopulatory DA response to an estrous female.
      The present study investigated the time courses of restoration, rather than loss,
      of the MPOA DA response to a receptive female and of copulation in long-term
      castrates. Male rats were castrated and tested for loss of copulatory ability 21
      days later. They then received 2, 5, or 10 daily subcutaneous injections of
      testosterone propionate (TP, 500 microg) or oil. Microdialysate samples were
      collected from the MPOA during baseline, exposure to a female behind a barrier,
      and copulation. Extracellular DA was measured using HPLC-EC. None of the six 2
      day-TP-treated animals copulated, nor did they show elevated DA release in the
      MPOA in the presence of a receptive female. Five of the nine 5-day-TP-treated
      animals ejaculated; three intromitted without ejaculating; and one failed to
      copulate, with all but the noncopulating animal showing elevated DA release. All
      of the six 10-day-TP-treated animals copulated and also demonstrated an increase
      in MPOA DA. None of the oil controls copulated or showed an increase in DA
      release. Therefore, a consistent relationship between MPOA DA release during
      exposure to a receptive female and the subsequent ability of the male to copulate
      was observed.

PMID- 11300713
TI  - Angiotensin II elicits water seeking behavior and the water absorption response
      in the toad Bufo bufo.
AB  - Fully hydrated toads, Bufo bufo were acclimated to a simulated terrestrial
      habitat, with access to shelters and water. To get from the shelters to the
      water, the toads had to walk across the pan of an Ohaus balance and the body
      weights were recorded on a computer. Toads were placed inside shelters
      immediately following injection of human angiotensin II (A II), Thr(8)-saralasin,
      or Ringer's in the dorsal lymph sac, and their behavior was recorded continuously
      by video surveillance. The injection doses were 1-100 microg/100 g body weight A
      II and 100 microg/100 g body weight saralasin dissolved in 0.1 ml Ringer's;
      control animals received the same volume of Ringer's. The latency from injection
      to the initiation of water absorption behavior (WR) was significantly shorter in
      both A-II- and saralasin-injected toads, compared to controls. A-II- and
      saralasin-injected toads also spent significantly more time in the water than
      controls. The bladder depots when WR was terminated were significantly larger in
      A-II- or saralasin-injected toads than in controls. The stimulatory action of
      Thr(8)-saralasin, an antagonist of A II in mammals, on WR behavior in B. bufo
      suggests differences in receptor structure and/or receptor distribution between
      amphibians and mammals.

PMID- 11300714
TI  - Dominance, cortisol, and behavior in small groups of female cynomolgus monkeys
      (Macaca fascicularis).
AB  - The relationships among social rank, basal cortisol concentrations, and social
      behavior were assessed in adult female cynomolgus monkeys (Macaca fascicularis).
      Subjects were 157 unrelated, reproductively intact animals housed in 30 small
      groups. Rank determinations were made monthly. Blood samples were collected on
      two occasions, 4.5 and 7.5 months following initial group formation. Regular
      behavioral observations were conducted on a subset of animals over a period of 4
      weeks, 9 months following group formation. Analyses revealed that serum cortisol
      values were significantly correlated across the two sampling periods, with no
      significant change in absolute values. While social rank was positively
      correlated across both samples, there was no relationship between rank and
      cortisol. However, dominant and subordinate animals did differ in the rates of
      performance of aggressive and submissive behaviors. These data suggest that
      social rank does not influence baseline serum cortisol in adult female cynomolgus
      monkeys, despite stability in measures of rank and cortisol and the presence of
      the usual behavioral differences between dominants and subordinates.

PMID- 11300715
TI  - Social behavior and hormonal correlates during the perinatal period in Japanese
      macaques.
AB  - This work assessed the changes in both social interactions and estrogen
      metabolite excreted in feces in eight group-living Japanese macaques (Macaca
      fuscata). We tested the hypothesis that the social behavior of pregnant females
      shows significant changes during the late prepartum and early postpartum period.
      We also tested the hypothesis that the marked fluctuation in estrogen levels
      during the perinatal period is associated with the changes in social behavior. We
      found that pregnant females withdrew from the social life of their group in
      preparation for parturition and only slowly regained their normal social activity
      after delivery. These changes were correlated with the fluctuation in estrogen
      conjugate excreted in feces, giving further evidence that hormones can enhance
      responsiveness to the infant and may predict maternal competence in macaques. We
      also found that the high frequency of self-grooming by pregnant females during
      the perinatal period may be a functional way to improve the quality of care
      toward an infant by a simple shifting from the care for oneself to the care for
      the infant after parturition.

PMID- 11300716
TI  - Microarray applications in neuroscience.
AB  - Advances in all facets of technology from molecular biology to imaging and
      computational biology offer unprecedented opportunities for improving our
      understanding of the brain in health and disease. Oligonucleotide and cDNA
      microarray analysis, using a variety of "DNA chips," is a recently developed high
      throughput technique that allows for tour-de-force analysis of gene expression.
      We review this powerful technique, developed in genetics laboratories, with
      reference to applications in neurologic diseases in humans and the use of animal
      models. The typical microarray experiment is multistaged and includes preparation
      or purchase of arrays, preparation of target DNA and probe, target DNA
      hybridization, microarray scanning, and image analysis. The power and pitfalls of
      this technology are discussed in the context of neuroscience paradigms. Since
      unprecedented amounts of data are produced from microarray experiments,
      bioinformatics and modeling expertise are increasingly becoming critical
      components of this approach.

PMID- 11300717
TI  - Caspase-mediated suppression of glutamate (AMPA) receptor channel activity in
      hippocampal neurons in response to DNA damage promotes apoptosis and prevents
      necrosis: implications for neurological side effects of cancer therapy and
      neurodegenerative disorders.
AB  - DNA damage in neurons is implicated in the pathogenesis of several
      neurodegenerative disorders and may also contribute to the often severe
      neurological complications in cancer patients treated with chemotherapeutic
      agents. DNA damage can trigger apoptosis, a form of controlled cell death that
      involves activation of cysteine proteases called caspases. The excitatory
      neurotransmitter glutamate plays central roles in the activation of neurons and
      in processes such as learning and memory, but overactivation of ionotropic
      glutamate receptors can induce either apoptosis or necrosis. Glutamate receptors
      of the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) type mediate
      such physiological and pathological processes in most neurons. We now report that
      DNA damage can alter glutamate receptor channel activity by a mechanism involving
      activation of caspases. Whole-cell patch clamp analyses revealed a marked
      decrease in AMPA-induced currents after exposure of neurons to camptothecin, a
      topoisomerase inhibitor that induces DNA damage; N-methyl-d-aspartate (NMDA)
      induced currents were unaffected by camptothecin. The decrease in AMPA-induced
      current was accompanied by a decreased calcium response to AMPA. Pharmacological
      inhibition of caspases abolished the effects of camptothecin on AMPA-induced
      current and calcium responses, and promoted excitotoxic necrosis. Combined
      treatment with glutamate receptor antagonists and a caspase inhibitor prevented
      camptothecin-induced neuronal death. Caspase-mediated suppression of AMPA
      currents may allow neurons with damaged DNA to withdraw their participation in
      excitatory circuits and undergo apoptosis, thereby avoiding widespread necrosis.
      These findings have important implications for treatment of patients with cancer
      and neurodegenerative disorders.

PMID- 11300718
TI  - Early Neurodegeneration after Hypoxia-Ischemia in Neonatal Rat Is Necrosis while
      Delayed Neuronal Death Is Apoptosis.
AB  - We used silver staining to demonstrate neuronal cell body, axonal, and terminal
      degeneration in brains from p7 rat pups recovered for 0, 1.5, 3, 6, 24, 48, 72 h,
      and 6 days following hypoxia-ischemia. We found that initial injury is evident in
      ipsilateral forebrain by 3 h following hypoxia-ischemia, while injury in ventral
      basal thalamus develops at 24 h. A secondary phase of injury occurs at 48 h in
      ipsilateral cortex, but not until 6 days in basal ganglia. Initial injury in
      striatum and cortex is necrosis, but in thalamus the neurodegeneration is
      primarily apoptosis. Degeneration also occurs in bilateral white matter tracts,
      and in synaptic terminal fields associated with apoptosis in regions remote from
      the primary injury. These results show that hypoxia-ischemia in the developing
      brain causes both early and delayed neurodegeneration in specific systems in
      which the morphology of neuronal death is determined by time, region, and
      potentially by patterns of neuronal connectivity.

PMID- 11300720
TI  - Death of motoneurons induced by trophic deprivation or by excitotoxicity is not
      prevented by overexpression of SMN.
AB  - The telomeric copy of the survival motor neuron gene (SMN1) is deleted or mutated
      in all spinal muscular atrophy (SMA) patients and these patients present mainly a
      loss in spinal motoneurons. Although studies performed in HeLa cells suggest that
      SMN may be involved in the biogenesis and possibly in recycling of spliceosomal
      small nuclear ribonucleoproteins (snRNPs), no link has been established between
      this function and the consequence of the absence of SMN in the specific loss of
      motoneurons. We attempted to answer the question of whether SMN plays a direct
      role in motoneuron survival by transducing cultured motoneurons with lentiviral
      vectors coding either for an antisense Smn mRNA or for full-length or truncated
      forms of SMN. We studied their effect on survival under different anti- or
      proapoptotic culture conditions. Our results show that increased levels of SMN
      are unable to protect motoneurons from death induced by trophic deprivation or by
      excitotoxicity. These results suggest that SMN is not a survival factor per se
      for motoneurons. In addition, overexpression of a truncated form of SMN shown to
      induce a modified subcellular localization and to exert a dominant-negative
      effect on snRNP biogenesis and RNA splicing in HeLa cells was ineffective in
      modifying both localization and survival in motoneurons.

PMID- 11300719
TI  - Alterations in cortical and basal ganglia levels of opioid receptor binding in a
      rat model of l-DOPA-induced dyskinesia.
AB  - Opioid receptor-binding autoradiography was used as a way to map sites of altered
      opioid transmission in a rat model of l-DOPA-induced dyskinesia. Rats with
      unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3
      week treatment with l-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide),
      causing about half of them to develop dyskinetic-like movements on the side of
      the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-,
      and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the
      globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the
      premotor-cingulate cortex. The dopamine-denervating lesion alone caused an
      ipsilateral reduction in opioid radioligand binding in the CPu, GP, and SN, but
      not in the cerebral cortex. Chronic l-DOPA treatment affected opioid receptor
      binding in both the basal ganglia and the cerebral cortex, producing changes that
      were both structure- and receptor-type specific, and closely related to the motor
      response elicited by the treatment. In the basal ganglia, the most clear-cut
      differences between dyskinetic and nondyskinetic rats pertained to kappa opioid
      sites. On the lesioned side, both striatal and nigral levels of kappa binding
      densities were significantly lower in the dyskinetic group, showing a negative
      correlation with the rats' dyskinesia scores on one hand and with the striatal
      expression of opioid precursor mRNAs on the other hand. In the cerebral cortex,
      levels of mu and delta binding site densities were bilaterally elevated in the
      dyskinetic group, whereas kappa radioligand binding was specifically increased in
      the nondyskinetic cases and showed a negative correlation with the rats'
      dyskinesia scores. These data demonstrate that bilateral changes in cortical
      opioid transmission are closely associated with l-DOPA-induced dyskinesia in the
      rat. Moreover, the fact that dyskinetic and nondyskinetic animals often show
      opposite changes in opioid radioligand binding suggests that the motor response
      to l-DOPA is determined, at least in part, by compensatory adjustments of brain
      opioid receptors.

PMID- 11300721
TI  - Complement association with neurons and beta-amyloid deposition in the brains of
      aged individuals with Down Syndrome.
AB  - To study the link between beta-amyloid (Abeta) and neuroinflammation, we examined
      the levels of complement as a function of age and extent of Abeta deposition in
      Down Syndrome (DS) brain. C1q, the first component of the complement cascade, was
      visualized using immunohistochemistry in the frontal, entorhinal cortex, and
      hippocampus of 12 DS ranging from 31 to 69 years of age. C1q was consistently
      associated with thioflavine-S positive Abeta plaques in DS brain and increased
      with more extensive age-dependent Abeta deposition. In contrast, little or no C1q
      labeling was associated with diffuse or thioflavine-S negative Abeta deposits.
      Neurons in the hippocampus and entorhinal cortex, but less frequently in frontal
      cortex, were C1q positive in DS cases with sufficient neuropathology to have a
      diagnosis of Alzheimer's disease. C1q-positive neurons were associated with
      activated microglia. These results provide evidence for Abeta-mediated
      inflammatory factors contributing to the rapid accumulation of neuropathology in
      DS brain.

PMID- 11300722
TI  - The protein 4.1 tumor suppressor, DAL-1, impairs cell motility, but regulates
      proliferation in a cell-type-specific fashion.
AB  - The neurofibromatosis 2 (NF2) tumor suppressor belongs to the Protein 4.1 family
      of molecules that link the actin cytoskeleton to cell surface glycoproteins. We
      have previously demonstrated that the NF2 protein, merlin, can suppress cell
      growth in vitro and in vivo as well as impair actin cytoskeleton-associated
      processes, such as cell spreading, attachment, and motility. Recently, we
      determined that expression of a second Protein 4.1 tumor suppressor, DAL-1, was
      lost in 60% of sporadic meningiomas, but not schwannomas. In this report, we
      demonstrate that DAL-1 suppresses cell proliferation in meningioma, but not
      schwannoma cells. Similar to merlin, DAL-1 interacts with other ERM proteins and
      betaII-spectrin, but not the merlin interactor protein, SCHIP-1. In addition, we
      report the identification of the full-length DAL-1 tumor suppressor, termed
      KIAA0987. Collectively, these results suggest that the two Protein 4.1 meningioma
      tumor suppressors, merlin and DAL-1, may be functionally distinct proteins with
      different mechanisms of action.

PMID- 11300723
TI  - Primary myopathy and accumulation of PrPSc-like molecules in peripheral tissues
      of transgenic mice expressing a prion protein insertional mutation.
AB  - A nine-octapeptide insertional mutation in the prion protein (PrP) gene is
      associated with an inherited variant of Creutzfeldt-Jakob disease in humans.
      Transgenic mice that express the mouse PrP homologue of this mutation (designated
      PG14) under control of a PrP promoter display a progressive neurological disorder
      characterized by ataxia, apoptosis of cerebellar granule cells, and accumulation
      in the brain of mutant PrP molecules that display the biochemical hallmarks of
      PrP(Sc), the pathogenic isoform of PrP. In this report, we have investigated the
      expression of PG14 PrP in the peripheral tissues of these mice. We found highest
      levels of mutant PrP in the brain and spinal cord, intermediate levels in
      skeletal muscle, heart, and testis and low levels in kidney, lung, spleen,
      intestine, and stomach. Up to 70% of the PG14 PrP expressed in peripheral tissues
      was detergent-insoluble, and digestion with low concentrations of proteinase K
      yielded a PrP 27-30 fragment. These results suggest that the mutant protein was
      converted to a physical state reminiscent of PrP(Sc), although its infectivity
      remains to be determined. Histological analysis of skeletal muscle, one of the
      peripheral tissues with the highest level of PG14 PrP, revealed features
      indicative of a progressive, primary myopathy, including central nuclei, necrotic
      and regenerating fibers, and variable fiber size. These results indicate that the
      PG14 mutation structurally alters the protein in a way that promotes conversion
      to a PrP(Sc)-like state, regardless of the tissue context, and suggest that
      accumulation of PrP(Sc) can have deleterious effects on skeletal muscle cells as
      well as on neurons.

PMID- 11300724
TI  - Enhanced proliferation of lymphoblasts from patients with Alzheimer dementia
      associated with calmodulin-dependent activation of the na+/H+ exchanger.
AB  - We have recently reported that lymphoblasts from late onset Alzheimer's disease
      (AD) patients show distinct intracellular pH homeostatic features than those
      obtained from age-matched healthy donors. Here we report that another distinct
      feature of AD lymphoblasts is their increased rate of proliferation in serum
      containing medium, suggesting a different responsiveness of AD cells to serum
      activators. The increased proliferation of AD cells was accompanied by
      intracellular alkalinization and was prevented by blockers of the plasma membrane
      Na+/H+ antiporter (NHE), indicating that the exchanger had to be activated to
      elicit the cellular responses. The activity of this exchanger can be controlled
      through several signaling pathways, but only the inhibition of calmodulin
      activity impeded the serum-induced intracellular alkalinization and enhanced
      proliferation of AD cells. In contrast, the inhibition of calmodulin did not
      alter the rate of proliferation of normal cells. Thus, it seems plausible to
      conclude that the enhanced proliferation of AD cells is the result of a surface
      receptor-mediated activation of the Ca(2+)-calmodulin signaling pathway. Our
      observations add further support in favor that AD may be considered a systemic
      disease which underlying etiopathogenic mechanism may be an altered
      responsiveness to cell activating agents. Thus, the use of lymphoblastoid cells
      from AD patients may be a useful model to investigate cell biochemical aspects of
      this disease.

PMID- 11300725
TI  - Sublethal concentrations of prion peptide PrP106-126 or the amyloid beta peptide
      of Alzheimer's disease activates expression of proapoptotic markers in primary
      cortical neurons.
AB  - Neurodegenerative disorders such as prion diseases and Alzheimer's disease (AD)
      are characterized by neuronal dysfunction and accumulation of amyloidogenic
      protein. In vitro studies have demonstrated that these amyloidogenic proteins can
      induce cellular oxidative stress and therefore may contribute to the neuronal
      dysfunction observed in these illnesses. Although the neurotoxic pathways are not
      fully elucidated, recent studies in AD have demonstrated up-regulation of
      caspases in neurons treated with amyloid beta (Abeta) peptide, suggesting
      involvement of apoptotic processes. To examine the role of proapoptotic pathways
      in prion diseases we treated primary mouse cortical neurons with the toxic prion
      protein peptide PrP106-126 and measured caspase activation and annexin V binding.
      We found that PrP106-126 induced a rapid and marked elevation in caspase 3, 6,
      and 8-like activity in neuronal cultures. Increased annexin V binding was
      observed predominantly on cortical cell neurites in peptide-treated cultures.
      Interestingly, these effects were induced by sublethal (5-50 microM) or lethal
      (100-200 microM) concentrations of PrP106-126. Sublethal concentrations of PrP106
      126 maintained elevated caspase activation for at least 10 days with no loss of
      cell viability. Abeta1-40 also up-regulated caspase 3 activity and annexin V
      binding at both sublethal (5 microM) and lethal (25 microM) concentrations. There
      were no changes to proapoptotic marker expression in cultures treated with
      scrambled PrP106-126 (200 microM) or Abeta1-28 (25 microM) peptides. These
      studies demonstrate that amyloidogenic peptides can induce prolonged activation
      of proapoptotic marker expression in cultured neurons even at sublethal
      concentrations. These effects could contribute to chronic neuronal dysfunction
      and increase susceptibility to additional metabolic insults in neurodegenerative
      disorders. If so, targeting of therapeutic strategies against neuronal caspase
      activation early in the disease course could be beneficial in AD and prion
      diseases.

PMID- 11300726
TI  - Genetic analysis of synphilin-1 in familial Parkinson's disease.
AB  - alpha-Synuclein is present in Lewy bodies of patients with both sporadic and
      familial Parkinson's disease. However, pathogenic mutations Ala30Pro and Ala53Thr
      in alpha-synuclein are rare causes of disease. Synphilin-1 has been demonstrated
      to associate with alpha-synuclein and promote the formation of cytosolic
      inclusions in vitro. Two-point genetic linkage analysis of a dinucleotide repeat
      within the synphilin-1 gene initially implicated this locus as a cause of
      Parkinson's disease in three of nine families. However, subsequent haplotype,
      sequencing, and association analyses in these three families and an independent
      case-control series suggest that variability within the locus does not confer
      susceptibility to Parkinson's disease.

PMID- 11300727
TI  - Prion protein affects Ca2+-activated K+ currents in cerebellar purkinje cells.
AB  - The prion protein (PrPC) has a primary role in the pathogenesis of transmissible
      spongiform encephalopathies. Its physiological function is not known yet. Altered
      late afterhyperpolarization has been observed in hippocampal CA1 pyramidal cells
      of prion protein-deficient mice (Prnp(0/0) mice) presumably caused by a
      disruption of Ca2+-activated K+ currents. An alteration of these currents has
      been recently described in scrapie-infected animals, and loss of function of PrPC
      has been put forward as one possible pathophysiological mechanism in prion
      diseases. This work focuses on patch-clamp studies of Ca2+-activated K+ currents
      in cerebellar Purkinje cells in the slice preparation of Prnp(0/0) mice as well
      as of transgenic mice. A significant correlation between PrPC expression in
      Purkinje cells and the maximal amplitude of TEA-insensitive Ca2+-activated K+
      currents was observed, with reduced current amplitudes in Prnp(0/0) mice and a
      rescue of the phenotype in transgenic mice where PrPC had been reintroduced.
      Further studies of the intracellular free calcium concentration revealed an
      alteration of the maximal increase of intracellular calcium concentration with
      depolarization in the Prnp(0/0) mouse Purkinje cells. These data provide strong
      evidence that Ca2+-activated K+ currents in Prnp(0/0) mice are reduced due to an
      alteration of intracellular calcium homeostasis.

PMID- 11300728
TI  - Alzheimer's disease-like alterations in peripheral cells from presenilin-1
      transgenic mice.
AB  - Many cases of early-onset inherited Alzheimer's disease (AD) are caused by
      mutations in the presenilin-1 (PS1) gene. Expression of PS1 mutations in cell
      culture systems and in primary neurons from transgenic mice increases their
      vulnerability to cell death. Interestingly, enhanced vulnerability to cell death
      has also been demonstrated for peripheral lymphocytes from AD patients. We now
      report that lymphocytes from PS1 mutant transgenic mice show a similar
      hypersensitivity to cell death as do peripheral cells from AD patients and
      several cell culture systems expressing PS1 mutations. The cell death-enhancing
      action of mutant PS1 was associated with increased production of reactive oxygen
      species and altered calcium regulation, but not with changes of mitochondrial
      cytochrome c. Our study further emphasizes the pathogenic role of mutant PS1 and
      may provide the fundamental basis for new efforts to close the gap between
      studies using neuronal cell lines transfected with mutant PS1, neurons from
      transgenic animals, and peripheral cells from AD patients.

PMID- 11300729
TI  - Upregulation of striatal preproenkephalin gene expression occurs before the
      appearance of parkinsonian signs in 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine
      monkeys.
AB  - GABA and enkephalin-utilizing efferents from the striatum to the external segment
      of the pallidal complex (GPe) are thought to be overactive in Parkinson's disease
      (PD). This overactivity is generally held to play a major role in the genesis of
      parkinsonian symptoms, which are thought to appear when dopaminergic neuronal
      death exceeds a critical threshold. Little is known, however, regarding the
      activity of this pathway during disease progression and more particularly, prior
      to the emergence of parkinsonian symptoms. In order to test the hypothesis that
      an upregulation of striatal preproenkephalin-A (PPE-A) mRNA levels occurs before
      the appearance of parkinsonian motor disabilities, the present study assessed PPE
      A mRNA expression and striatal dopamine (DA) content following a chronic 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration protocol in monkeys
      that produces a progressive parkinsonian state. Groups ranged from normal to full
      parkinsonian through asymptomatic lesioned monkeys. The key finding of this study
      is that PPE-A expression is already upregulated in asymptomatic-lesioned monkeys
      showing a marked DA depletion (56%). Importantly, this up-regulation is
      restricted to motor regions of the basal ganglia circuitry. The increased PPE-A
      mRNA expression observed in asymptomatic, but DA-depleted animals, supports our
      initial hypothesis of such an upregulation occurring before the appearance of
      parkinsonian motor disabilities. Furthermore, when considered with recent
      electrophysiological and histochemical data, these findings question the
      functional significance of upregulated enkephalin transmission in the indirect
      striatopallidal pathway.

PMID- 11300730
TI  - Seasonal affective disorder and serotonin-related polymorphisms.
AB  - Disturbances in central serotonergic systems have been hypothesized to be
      involved in seasonal affective disorder (SAD). Association between SAD and the
      shorter allele of the serotonin transporter promoter repeat length polymorphism
      (5-HTTLPR) has been reported in an American sample. We have genotyped 82 SAD
      patients and 82 healthy controls from Sweden, Finland, and Germany for this and
      five other polymorphisms in the genes coding for serotonin receptors 5-HT2A and 5
      HT2C, tryptophan hydroxylase and white. No associations with SAD or seasonality
      (seasonal variations in mood and behavior) were detected. Although minor effects
      cannot be excluded, our results suggest that these polymorphisms do not play a
      major role in the pathogenesis of SAD in the northern European population.

PMID- 11300731
TI  - Intrahippocampal scopolamine impairs both acquisition and consolidation of
      contextual fear conditioning.
AB  - Lesions of the dorsal hippocampus have been shown to disrupt both the acquisition
      and the consolidation of memories associated with contextual fear (fear of the
      place of conditioning), but do not affect fear conditioning to discrete cues
      (e.g., a tone). Blockade of central muscarinic cholinergic receptor activation
      results in selective acquisition deficits of contextual fear conditioning, but
      reportedly has little effect on consolidation. Here we show for the first time
      that direct infusion of the muscarinic cholinergic receptor antagonist,
      scopolamine, into the dorsal hippocampus produces a dose-dependent deficit in
      both acquisition and consolidation of contextual fear conditioning, while having
      no impact on simple tone conditioning.

PMID- 11300732
TI  - CAMKII inhibition in the parabrachial nuclei elicits conditioned taste aversion
      in rats.
AB  - The conditioned taste aversion (CTA) paradigm was used to assess the role of
      Ca(2+)/calmodulin-dependent protein kinase (CAMKII) in associative learning.
      KN62, a specific inhibitor of CAMKII, was injected into the parabrachial nuclei
      (PBN) either immediately after saccharin drinking (CS) or after saccharin
      drinking and i.p. injection of LiCl (US). Injection of KN62 into the PBN after
      saccharin drinking elicited clear CTA (Exp. 1). This effect was dosage-dependent
      and site-specific (Exp. 2). The results are discussed in relation with an earlier
      report showing that CTA acquisition is disrupted by injection of
      Ca(2+)/phospholipid-dependent protein kinase (PKC) inhibitor chelerythrine into
      the PBN during CS-US interval. It is suggested that the principal
      serine/threonine kinases play different roles in CTA learning: whereas PKC
      activity is necessary for the gustatory short-term memory formation, CAMKII acts
      similarly to the US itself-an unexpected role of CAMKII in associative learning.

PMID- 11300733
TI  - Emotionally arousing pictures increase blood glucose levels and enhance recall.
AB  - Arousal enhances memory in human participants and this enhancing effect is likely
      due to the release of peripheral epinephrine. As epinephrine does not readily
      enter the brain, one way that peripheral epinephrine may enhance memory is by
      increasing circulating blood glucose levels. The present study investigated the
      possibility that emotionally arousing color pictures would improve memory and
      elevate blood glucose levels in human participants. Blood glucose levels were
      measured before, 15 min, and 30 min after male university students viewed 60
      emotionally arousing or relatively neutral pictures. Participants viewed each
      picture for 6 s and then had 10 s to rate the arousal (emotional intensity) and
      valence (pleasantness) of each picture. A free-recall memory test was given 30
      min after the last picture was viewed. Although the emotionally arousing and
      neutral picture sets were given comparable valence ratings, participants who
      viewed the emotionally arousing pictures rated the pictures as being more
      arousing, recalled more pictures, and had higher blood glucose levels after
      viewing the pictures than did participants who viewed the neutral pictures. These
      findings indicate that emotionally arousing pictures increase blood glucose
      levels and enhance memory, and that this effect is not due to differences in the
      degree of pleasantness of the stimuli. These findings support the possibility
      that increases in circulating blood glucose levels in response to emotional
      arousal may be part of the biological mechanism that allows emotional arousal to
      enhance memory.

PMID- 11300734
TI  - Functional recovery of skilled forelimb use in rats obliged to use the impaired
      limb after grafting of the frontal cortex lesion with homotopic fetal cortex.
AB  - The long-term effect of transplanting embryonic frontal cortex into a unilateral
      frontal cortex lesion has been studied in adult rats. Before surgery, activity in
      an open field, muscular strength of both forelimbs, and performance in a paw
      reaching-for-food task were scored in 26 rats. In 21 animals a unilateral cortex
      lesion was then made in the forelimb motor area of the hemisphere contralateral
      to the preferred paw in the paw-reaching-for-food task, while the other 5 animals
      were sham-operated. On retesting, the lesion animals changed the preferred paw. A
      solid homotopic transplant of embryonic tissue (embryonic day 17) was then placed
      in the lesion cavity in 11 of the lesion rats. Three months later neither lesion
      alone nor lesion plus transplantation affected open field behavior and muscular
      strength, but the lesion permanently affected performance in the paw-reaching-for
      food task, as shown by a change of preferred paw and a functional deficit in the
      paw contralateral to the lesion. Transplantation ameliorated the deficits caused
      by the lesion, but this was only evident when animals were forced to reach with
      the paw contralateral to the lesion plus transplant. The behavioral results were
      independent of the size of the lesion and graft. Connections between graft and
      host tissue were studied by means of the fluorescent tracer 1,1'-dioctadecyl
      3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI). A dense array of labeled
      fibers was found in the host cortex adjacent to the transplant. The results
      suggest that functional recovery depends on grafting but is only evident when the
      animal is obliged to use the affected limb.

PMID- 11300735
TI  - Long-term memory formation in the chick requires mobilization of ryanodine
      sensitive intracellular calcium stores.
AB  - Training chicks (Gallus domesticus) on a one-trial passive avoidance task results
      in transient and time-dependent enhanced increases in N-methyl-d-aspartate- or
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-stimulated intracellular
      calcium concentration in synaptoneurosomes isolated from a specific forebrain
      region, the intermediate medial hyperstriatum ventrale. This increase could
      result from either calcium entry from the extracellular medium or from
      mobilization of intracellular calcium stores. We have therefore examined the
      effects of dantrolene, an inhibitor of calcium release from the intracellular
      ryanodine-sensitive store, on these processes. Dantrolene, 50 nmol per hemisphere
      injected intracerebrally 30 min pre- or 30 min posttraining, blocked longer term
      memory for the passive avoidance task, whereas memory for the task was unaffected
      when dantrolene was injected at earlier or later times. Preincubation of
      synaptoneurosomes, isolated from the intermediate hyperstriatum ventrale 10 min
      after training, with 100 nM dantrolene abolished the enhanced training-induced
      increase in intracellular calcium concentration elicited by 0.5 mM N-methyl-d
      aspartate. By contrast, the training-induced enhancement of the alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate-stimulated increase in intracellular
      calcium concentration in synaptoneurosomes prepared 6 h posttraining was
      unaffected by preincubation with dantrolene, which was not amnestic at this time.
      Calcium release from ryanodine-sensitive intracellular stores may thus be a
      necessary stage in the early phase of the molecular cascade leading to the
      synaptic modulation required for long-term memory storage.

PMID- 11300736
TI  - The moving fire hydrant experiment: movement of objects to a new location
      reelicits marking in rats.
AB  - Three experiments were carried out to investigate the influence of object
      relocation on object marking in an open field by hooded and albino rats. Object
      marking was reelicited when an object was moved to a new location in the second
      half of an open field test. Control conditions revealed that an object briefly
      moved and returned to the original location elicited no more marking than a
      stationary object. The higher level of marking of the relocated object suggests
      that object marking may provide an index of spatial knowledge. The implication of
      spatial knowledge in controlling marking behavior is congruent with observations
      that rats with hippocampal damage show increased marking.

PMID- 11300737
TI  - Differential interaction of platelet-activating factor and NMDA receptor function
      in hippocampal and dorsal striatal memory processes.
AB  - The interaction between platelet activating factor (PAF) and NMDA receptor
      function in hippocampal and dorsal striatal memory processes was examined. In
      both a hidden and a visible platform water maze task, peripheral post-training
      injection of MK-801 (0.05 mg/kg) impaired memory. Post-training intrahippocampal
      infusions of PAF (1.0 microg/0.5 microl) enhanced memory in the hidden platform
      task, while intradorsal striatal infusion of PAF (1.0 microg/0.5 microl) enhanced
      memory in the visible platform task. The memory impairing effects of post
      training injection of MK-801 was blocked by concurrent intrahippocampal infusion
      of PAF. In contrast, post-training injection of MK-801 blocked the memory
      enhancing effects of concurrent intradorsal striatal infusion of PAF. The results
      suggest that (1) the memory enhancing effects of intracerebral PAF infusion
      involve an interaction with NMDA receptor function, and (2) the nature of this
      interaction may represent a differential mechanism mediating the distinct roles
      of the hippocampus and dorsal striatum in cognitive memory and stimulus-response
      habit formation, respectively.

PMID- 11300738
TI  - Fluctuations in brain glucose concentration during behavioral testing:
      dissociations between brain areas and between brain and blood.
AB  - Traditional beliefs about two aspects of glucose regulation in the brain have
      been challenged by recent findings. First, the absolute level of glucose in the
      brain's extracellular fluid appears to be lower than previously thought. Second,
      the level of glucose in brain extracellular fluid is less stable than previously
      believed. In vivo brain microdialysis was used, according to the method of zero
      net flux, to determine the basal concentration of glucose in the extracellular
      fluid of the striatum in awake, freely moving rats for comparison with recent
      hippocampal measurements. In addition, extracellular glucose levels in both the
      hippocampus and the striatum were measured before, during, and after behavioral
      testing in a hippocampus-dependent spontaneous alternation task. In the striatum,
      the resting extracellular glucose level was 0.71 mM, approximately 70% of the
      concentration measured previously in the hippocampus. Consistent with past
      findings, the hippocampal extracellular glucose level decreased by up to 30 +/-
      4% during testing; no decrease, and in fact a small increase (9 +/- 3%), was seen
      in the striatum. Blood glucose measurements obtained during the same testing
      procedure and following administration of systemic glucose at a dose known to
      enhance memory in this task revealed a dissociation in glucose level fluctuations
      between the blood and both striatal and hippocampal extracellular fluid. These
      findings suggest, first, that glucose is compartmentalized within the brain and,
      second, that one mechanism by which administration of glucose enhances memory
      performance is via provision of increased glucose supply from the blood
      specifically to those brain areas involved in mediating that performance.

PMID- 11300739
TI  - Chronic amphetamine exposure during the preweanling period does not affect
      avoidance learning or novelty-seeking of adult rats.
AB  - The purpose of the present study was to determine whether exposure to amphetamine
      during the preweanling period would impact the learning or reward processes of
      rats tested in adulthood. In three experiments we examined whether amphetamine
      treatment (0-10 mg/kg per day) on postnatal days 11-17 altered the subsequent
      performance of adult Sprague-Dawley rats on a step-down passive avoidance, active
      avoidance, or novelty-seeking task. There was no evidence that postnatal
      amphetamine exposure affected performance on any of these tasks. These results
      suggest that the long-term impact of pre- and postnatal psychostimulant exposure
      differs, because in utero stimulant treatment is known to produce learning
      deficits and decrease reinforcement efficacy of rats tested in adulthood.

PMID- 11300740
TI  - Involvement of the sigma receptor in passive-avoidance learning in the day-old
      chick during the second wave of neuronal activity.
AB  - The specific sigma-receptor agonist (+)-SKF 10047 and antagonist BD 1047 were
      used to investigate whether this receptor was involved in passive-avoidance
      training in the day-old chick. We found 300 microM (+)-SKF 10047 to be amnesic
      when injected into the lobus parolfactorius 5 h after training (p < .01). Higher
      or lower concentrations of (+)-SKF 10047 did not disrupt memory formation. The
      amnesia produced by the efficacious dose of (+)-SKF 10047 was reversed by the
      specific antagonist, BD 1047. It is suggested that the sigma-receptor may exert
      its effect on passive-avoidance memory consolidation during the later stages of
      long-term memory formation by modulation of memory-related neurotransmission.

PMID- 11300741
TI  - Transforming growth factor beta-1 stimulates articular chondrocyte elaboration of
      matrix vesicles capable of greater calcium pyrophosphate precipitation.
AB  - Objective To determine the role of transforming growth factor beta1 (TGFbeta) in
      early calcium pyrophosphate formation by measuring its effects on articular
      chondrocyte matrix vesicle (MV) formation, specific activity of the inorganic
      pyrophosphate(PPi)-generating enzyme nucleoside triphosphate pyrophospho
      hydrolase (NTPPPH) and biomineralization capacity. Methods MV elaborated from
      mature porcine chondrocyte monolayers+/-TGFbeta were compared for protein
      content, NTPPPH activity, and ATP-dependent biomineralization. Precipitation of
      calcium pyrophosphate mineral phases by MV was determined by a radiometric assay
      and by Fourier transform infrared spectroscopy (FTIR). Results MV from monolayers
      exposed to TGFbeta were enriched in NTPPPH activity compared to MV from control
      monolayers (P< 0.01) and precipitated more calcium/mg MV protein than controls
      (P</= 0.01). FTIR spectra of mineral generated by monolayer-elaborated MV were
      consistent with poorly crystalline CPPD. Conclusions TGFbeta is capable of
      increasing the capacity of articular chondrocyte-derived MV to generate PPi via
      NTPPPH and precipitate calcium in the form of CPPD mineral. These data support
      the concept that this growth factor plays a key role in cartilage matrix CPPD
      deposition.

PMID- 11300742
TI  - TGF-beta1 as a prognostic factor in the process of early osteoarthrosis in the
      rabbit knee.
AB  - OBJECTIVE: To assess changes in knee joint fluid concentrations of transforming
      growth factor-beta1 (TGF-beta1) and proteoglycan (PG) fragments during the early
      course of post-traumatic osteoarthrosis (OA) after meniscectomy in the rabbit
      knee, and to ascertain whether the concentrations of these substances shortly
      after operation could be used as prognostic markers for the OA process. DESIGN:
      In 15 rabbits with medial meniscectomy in one knee and a sham operation in the
      other knee, synovial lavage fluid samples were taken repeatedly, before
      operation, every third week post-operatively until 12 weeks, thereafter every
      sixth week, and at death. Five rabbits each were killed at 13, 25 and 40 weeks.
      Synovial lavage fluid samples from five non-operated rabbits served as controls.
      At death, two histological scores were formed that characterized the highest
      (MAX) and the overall (ALL) degree of OA changes in each joint. RESULTS: TGF
      beta1 and PG fragment concentrations in synovial lavage fluid correlated highly
      (R=0.81, P< 0.001). Both OA scores were higher in meniscectomized than controls
      (P< 0.05). The synovial lavage fluid concentration of TGF-beta1 at 3 weeks, but
      no other time point, correlated to the histological scores (ALL, R=0.58; MAX,
      R=0.52;P< 0.001). CONCLUSION: Higher concentrations of TGF-beta1 in synovial
      lavage fluid early after surgery seemed indicative for the later development of
      more severe OA changes in contrast to lower concentrations. The association
      between TGF-beta1 and the changes found later in the cartilage was underlined by
      the high correlations between this substance and PG fragment concentrations in
      synovial lavage fluid at all time points.

PMID- 11300743
TI  - Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and
      osteoarthritis. Involvement of YKL-40 in the joint pathology.
AB  - OBJECTIVE: The presence of YKL-40 (human cartilage glycoprotein 39) in synovium,
      cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid
      arthritis and osteoarthritis (OA) were related to histopathological changes in
      synovium and cartilage and to serum YKL-40 and other biochemical markers.
      METHODS: The localization of YKL-40 in synovium and cartilage was determined by
      immunohistochemistry. Synovial inflammation was estimated histologically and by
      magnetic resonance imaging (MRI). Biochemical markers of inflammation, neutrophil
      activation and cartilage metabolism were analysed. YKL-40 concentrations in serum
      and SF were determined by RIA and ELISA. RESULTS: In the synovium YKL-40 positive
      cells were found in lining and stromal cells (macrophages) and the number of YKL
      40 positive cells was related to the degree of synovitis. In arthritic cartilage,
      YKL-40 was located to chondrocytes. YKL-40 levels in SF were higher in RA
      patients with moderate/severe or none/slight synovitis of the knee joint compared
      to OA patients with moderate/severe or none/slight synovitis. SF YKL-40
      correlated with the synovial membrane and the joint effusion volumes determined
      by magnetic resonance imaging (MRI) and with other biochemical markers of
      intercellular matrix metabolism. SF YKL-40 was higher than serum YKL-40, and a
      relationship existed between the YKL-40 levels in SF and serum. Intraarticular
      glucocorticoid injection was followed by clinical remission and a decrease in
      serum YKL-40, which increased again at clinical relapse. CONCLUSIONS: YKL-40 in
      SF is derived from cells in the inflamed synovium, chondrocytes and SF
      neutrophils. Joint derived YKL-40 influences serum YKL-40. YKL-40 may be involved
      in the pathophysiology of the arthritic processes and reflect local disease
      activity.

PMID- 11300744
TI  - Localization of chondrocyte precursors in periosteum.
AB  - OBJECTIVE: Periosteal chondrogenesis is relevant to cartilage repair and fracture
      healing. Periosteum contains two distinct layers: a thick, outer fibrous layer
      and a thin, inner cambium layer which is adjacent to the bone. Specific
      chondrocyte precursors are known to exist in periosteum but have not yet been
      identified. In this study, the location of the chondrocyte precursors in
      periosteum was determined. METHOD: One hundred and twenty periosteal explants
      from 30 2-month-old NZ rabbits were cultured for up to 42 days.
      Histomorphological changes and spatio-temporal localization of Col. II mRNA and
      protein were analysed. RESULTS: On day 7, chondrocyte differentiation appeared in
      the most juxtaosseous region in the cambium layer. Col. II mRNA and protein were
      also evident in the same region. By day 14, chondrocyte differentiation
      progressed further into the juxtaosseous cambium layer, as did Col. II mRNA and
      protein. With growth of the neocartilage, the cambium layer gradually diminished
      to the extent that by 21-28 days it was no longer evident. Cartilage growth was
      significant and followed an appositional pattern, growing away from the fibrous
      layer. The fibrous layer remained essentially unchanged from 0-42 days, without
      evidence of hypertrophy or atrophy. Col. II mRNA expression was never seen in the
      fibrous layer. CONCLUSION: From these data, three conclusions can be drawn
      concerning chondrogenesis from periosteum: (1) the chondrocyte precursors are
      located in the cambium layer of periosteum; (2) chondrogenesis commences in the
      juxtaosseous area in the cambium layer and progresses from the juxtaosseous
      region to the juxtafibrous region of the cambium layer; (3) neocartilage growth
      is appositional, which displaces the fibrous layer away from the cartilage
      already formed, as new cartilage is formed between these two layers. These
      findings suggest that the least differentiated (stem or reserve) cells are
      located in the cambium layer furthest from the bone. CLINICAL RELEVANCE: These
      findings show that the chondrocyte precursors are located in the cambium layer of
      periosteum. Preservation of this layer is essential for chondrogenesis. As
      neocartilage growth is appositional, away from the fibrous layer, it can be
      expected that the new cartilage deposited in and adjacent to a periosteal graft
      would be expected to be located on the side of the cambium layer, rather than on
      the side of the fibrous layer of the graft.

PMID- 11300745
TI  - An analysis of 14 molecular markers for monitoring osteoarthritis. Relationship
      of the markers to clinical end-points.
AB  - OBJECTIVE: To investigate whether any of 14 serum and urine molecular markers
      (MMs) used to monitor osteoarthritis (OA) would be associated with particular
      clinical end-points. DESIGN: Thirty-nine OA patients were bled and urine
      collected at five time points: at baseline visit and at visits 1, 3, 6 and 12
      months later. Twelve clinical measurements were made and the concentrations of
      each of 14 MMs were determined. Principal component analysis, stepwise linear
      regression with backward elimination, and logistic regression were used to
      determine the correlations between MMs and clinical measures. RESULTS: Principal
      component analysis was used to reduce the 12 clinical measurements into three
      independent clinical clusters: baseline clinical assessments, changes in clinical
      assessments and signal joint measurements. The 14 MMs were similarly reduced to
      five MM clusters. Each of the three clinical clusters was correlated with a
      single but different MM cluster. Baseline clinical assessments were correlated
      with bone markers typified by hydroxylysyl pyridinoline (HP) crosslinks, swelling
      of the signal joint was correlated with inflammation markers, especially CRP, and
      the change in clinical assessments over the 1 year evaluation was correlated with
      TGFbeta1. There was no correlation between any of the skeletal markers and the
      clinical measures, a situation which draws attention to the need for a direct
      assessment of cartilage damage in OA to validate the use of cartilage markers.
      CONCLUSIONS: This study demonstrates statistical methodology for analysis of
      clinical trials using multiple MMs and clinical end-points. The patient numbers
      are sufficient to test hypotheses of relationships of single MMs such as CRP,
      TGFbeta1 and HP to clinical measures, but larger clinical trials are needed to
      validate hypotheses.

PMID- 11300746
TI  - Involvement of nitric oxide in chondrocyte cell death in chondro-osteophyte
      formation.
AB  - OBJECTIVE: To examine the nitric oxide (NO) production relevant to chondrocyte
      cell death in order to elucidate the mechanism of chondro-osteophyte formation in
      osteoarthrotic joints. DESIGN: Human chondro-osteophytes were obtained during
      total hip arthroplasty. Expression of inducible nitric oxide synthase (iNOS) mRNA
      was determined by in-situ hybridization. Localization of iNOS and nitrotyrosine
      at protein level were examined by immunohistochemistry. Cell death of
      chondrocytes were confirmed by both TUNEL method and transmission electron
      microscopy. RESULTS: The various populations of proliferative and hypertrophic
      chondrocytes expressed iNOS mRNA and iNOS as well as nitrotyrosine protein.
      Approximately 30% of hypertrophic chondrocytes forming chondro-osteophyte showed
      positive reaction to TUNEL staining. Electron microscopy confirmed both
      disintegrated and apoptotic chondrocytes in these zones. In the deep hypertrophic
      zone calcification was seen around each of the matrix vesicles and some masses of
      cell debris. CONCLUSION: Chondro-osteophyte formation involves NO production by
      chondrocytes. The expression and localization of iNOS and nitrotyrosine in
      chondro-osteophytes suggest the significant role of NO in chondrocyte hypertrophy
      and apoptosis.

PMID- 11300747
TI  - A novel microassay for the quantitation of the sulfated glycosaminoglycan content
      of histological sections: its application to determine the effects of Diacerhein
      on cartilage in an ovine model of osteoarthritis.
AB  - OBJECTIVE: A new micro-histological method of assessing the sulfated
      glycosaminoglycan (S-GAG) content in unstained histological sections of articular
      cartilage was developed and used to study the effects of orally administered
      Diacerhein (DIA) on joint cartilage in an ovine model of osteoarthritis (OA).
      METHODS: Twenty adult, age-matched Merino wethers were subjected to bilateral
      lateral meniscectomy, while 10 served as non-operated controls (NOC groups). Half
      of the operated sheep (N=10) remained untreated (MEN groups), while the other 10
      animals were given DIA (25 mg/kg orally) daily for 3 months, then 50 mg/kg daily
      for a further 6 months (DIA groups). Five animals each of the DIA, MEN and NOC
      groups, respectively, were sacrificed at 3 months post-operatively, and the
      remainder 6 months later. For the present study only one knee joint of each
      animal was used for histological processing. The tissues studied were from the
      lateral femoral condyles (LFC) and lateral tibial plateaux (LTP). Each of these
      joint regions was further subdivided into inner (I), middle (M), and outer (O)
      zones. Unstained histological sections from these AC regions and zones were then
      analysed for S-GAG content using the following procedure. Images of each section
      of 6 microm thickness were acquired using a flatbed scanner and the area
      determined with an image analysis software program. The sections were then
      transferred to wells of a microtiter plate, digested with papain and the S-GAG
      content quantitated using a modification of the 1,9-dimethylmethylene blue dye
      binding assay. The data was represented as microg S-GAG/mm(3)of each tissue
      section. These data were also compared with toluidine blue stained sections from
      the same paraffin blocks. RESULTS: The results obtained showed that the area of
      histological sections could be very accurately determined by computer assisted
      image analysis using a 10 mmx10 mm calibration grid. Cartilage sections of areas
      ranging from 1 mm(2)up to 25 mm(2)were analysed for S-GAG content with this
      simple technique. There was a linear relationship between section thickness (2-10
      microm) and S-GAG content per unit area (R(2)=0.993). Sections of 6 microm
      thickness were found to be optimal. S-GAG analyses of serial sections from tibial
      and femoral articular cartilage (I, M and O zones) revealed an average
      coefficient of variation of 7.0+/-2.3% (range 4.9-10.2%) confirming the accuracy
      and reproducibility of this assay method. A separate experiment showed that no
      significant losses of S-GAG occurred during the histological sample processing.
      The different regions and zones of the knee joint AC in the six experimental
      groups revealed variable levels of S-GAG which did not necessarily correlate with
      the histochemical distribution of toluidine blue staining. The major S-GAG
      changes occurred in the middle (lesion zone) and outer zones (hypertrophic zone)
      of both the LFC and LTP of the MEN groups. In the lesion (M) zone the S-GAG
      content was reduced while in the O zone levels were increased at both 3 and 6
      months post-surgery. In animals receiving Diacerhein S-GAG levels in the M zone
      were lower than or equivalent to those of non-drug treated OA or non-operated
      controls for both joint regions at 3 and 6 months. While the hypertrophic
      response in the outer zone of the LFC, as assessed by S-GAG content, was enhanced
      by drug treatment, the cartilage of the outer zones of the LTP was not affected
      by drug treatment. CONCLUSION: The results of this study have demonstrated that
      the S-GAG (and therefore proteoglycan [PG]) content in different cartilage zones
      of OA joints can be readily quantitated by direct biochemical analysis of
      unstained histological sections. By this means subtle changes in PG distribution
      in different cartilage zones, which were not evident using traditional
      histochemical staining methods, could be readily detected.

PMID- 11300748
TI  - High-efficiency non-viral transfection of primary chondrocytes and perichondrial
      cells for ex-vivo gene therapy to repair articular cartilage defects.
AB  - BACKGROUND: Primary perichondrial cells and chondrocytes have been used to repair
      articular cartilage defects in tissue engineering studies involving various
      animal models. Transfection of these cells with a gene that induces chondrocytic
      phenotype may form an ideal method to affect tissue engineering of articular
      cartilage. DESIGN: A protocol for high-efficiency transfection of primary
      perichondrial and cartilage cells was optimized. Plasmids carrying the marker
      beta-galactosidase (beta-gal), PTHrP and TGF-beta1 genes driven by a strong
      mammalian promoter were transfected into primary perichondrial cells and
      chondrocytes. A three-step method was used to achieve high efficiency of
      transfection: (1) permeabilization of primary cells using a mild detergent, (2)
      association of plasmid DNAs with a polycationic (poly-l-lysine) core covalently
      linked to a receptor ligand (transferrin), (3) introduction of cationic liposomes
      to form the quaternary complex. For in-vivo assessment, polylactic acid (PLA)
      scaffolds seeded with beta-gal transfected perichondrial cells were implanted
      into experimentally created osteochondral defects in rabbit knees for 1 week.
      RESULTS: The efficiency of transfection was determined to be over 70%in vitro.
      The transformed cells continued to express beta-gal, in vivo for the entire test
      period of 7 days. Furthermore, primary perichondrial cells transfected with TGF
      beta1 and PTHrP over-expressed their cognate gene products. CONCLUSION: The
      ability to transfect autologous primary perichondrial cells and chondrocytes with
      high efficiency using a non-viral system may form a first step towards tissue
      engineering with these transformed cells to repair articular cartilage defects.

PMID- 11300749
TI  - Rhein, an active metabolite of diacerein, down-regulates the production of pro
      matrix metalloproteinases-1, -3, -9 and -13 and up-regulates the production of
      tissue inhibitor of metalloproteinase-1 in cultured rabbit articular
      chondrocytes.
AB  - OBJECTIVE: Diacerein has proved to be effective in the treatment of
      osteoarthritis (OA). However, the precise action mechanism of diacerein on OA is
      not yet fully understood. Therefore, we investigated the effects of rhein, an
      active metabolite of diacerein, on the production of promatrix metalloproteinases
      (MMPs) and tissue inhibitors of metalloproteinase-1 (TIMP-1) in rabbit articular
      chondrocytes. DESIGN: Confluent rabbit chondrocytes were treated for 24 or 48 h
      with rhein, naproxen or dexamethasone in the presence of recombinant human IL
      1alpha (rhIL-1alpha). ProMMP-9/progelatinase B in the culture medium was
      monitored by gelatin zymography, and proMMP-1/procollagenase 1, proMMP
      3/prostromelysin 1, proMMP-13/procollagenase 3 and TIMP-1 were analysed by
      Western blot analysis. The steady-state levels of proMMP mRNAs were examined by
      Northern blot analysis. Total MMPs activity was also determined using FITC
      labeled casein. RESULTS: Rhein suppressed the rhIL-1alpha-induced production of
      proMMPs-1, -3, -9 and -13 in a dose-dependent manner (0.1-30 microM). The
      suppressed production of proMMPs-1 and -3 was accompanied by a decrease in the
      steady-state levels of their mRNAs. Interestingly, rhein increased the production
      of TIMP-1. These observations were further supported by the fact that rhein
      decreased the apparent total activity of MMPs in the culture medium. CONCLUSION:
      We have demonstrated that rhein, an active metabolite of diacerein down-regulates
      the gene-expression and production of proMMPs and up-regulates the TIMP-1
      production. The therapeutic effects of diacerein on OA may be due, at least in
      part, to the chondroprotective effect of rhein, its active metabolite.

PMID- 11300750
TI  - Ankle images digital analysis (AIDA): digital measurement of joint space width
      and subchondral sclerosis on standard radiographs.
AB  - OBJECTIVE: Reliable evaluation of joint space width and subchondral sclerosis of
      osteoarthritic joints is difficult. The present study describes a new digital
      method to analyse standard radiographs of the ankle. DESIGN: Standardized
      radiographs were taken of the ankle of 12 patients with severe osteoarthritis
      (OA) under full weight-bearing conditions, before treatment and 1 year after
      initiation of treatment. Treatment consisted of 3 months distraction of the tibio
      talar joint, for which clinical benefit has been shown previously. The width of
      the joint space was measured on digitized images of the radiographs by means of
      the newly developed semi-automatic digital technique called AIDA (Ankle Images
      Digital Analysis) and by means of the most widely used conventional analogue
      measurements. In addition, AIDA was used to assess subchondral sclerosis by
      measuring the intensity of the radiograph at fixed positions at the bone
      cartilage interface. RESULTS: AIDA appeared to be a reliable method for measuring
      small changes in joint space width and subchondral sclerosis because the intra-
      and interobserver variation was small. Mean JSW for two observers was 1.96 and
      2.00 mm, with mean differences between two observations of 0.05 and -0.01,
      respectively. Mean subchondral sclerosis in the tibia was 1.52 and 1.61 with mean
      differences between two observations of, respectively, 0.00 and 0.03. In addition
      to conventional measurements, AIDA could demonstrate a decrease in subchondral
      sclerosis as a result of joint distraction of 71% and 69% after 1 year for talus
      and tibia, respectively. CONCLUSION: The use of AIDA is preferable to the
      conventional analogue method for evaluating the severity of ankle OA, because the
      method provides quantitative data not only for the joint space width but also for
      subchondral sclerosis.

PMID- 11300751
TI  - Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis.
AB  - OBJECTIVE: A double-blind, placebo-controlled dose-finding study was performed in
      237 patients with predominantly unilateral knee osteoarthritis (OA) evaluating
      efficacy and safety of a new topical NSAID. DESIGN: The patients applied 3 g tid
      eltenac gel 0.1%, 0.3%, 1% or placebo gel over a period of 4 weeks. The patients
      were supplied with paracetamol tablets as an escape analgesic. Primary efficacy
      end-point was mean global pain in the week preceding the examinatio ns, evaluated
      on a visual analog scale (VAS). Secondary criteria were Lequesne's score ISK,
      Jezek score, muscle strength and dolorimeter measurements, walking time, clinical
      examination results of the knee joint and patient's and investigator's overall
      efficacy estimates. RESULTS: The graphical depiction of VAS and ISK suggested a
      dose-related efficacy, but the pre-planned statistical analysis did not show
      significant differences between treatments. In the patient subgroup with a higher
      degree of baseline severity of knee OA the ISK showed significant and relevant
      advantages of eltenac gel 1% to placebo at different examination times. Two
      patients each of the eltenac gel 1% group and the placebo group showed local
      intolerance reactions which subsided spontaneously. CONCLUSION: This study did
      not provide confirmatory proof of an efficacy of topical eltenac in patients with
      knee OA. Methodological pitfalls and possible responder subgroups are described.
      Despite the difficulties, dose-finding studies seem to be feasible even with
      topical NSAIDs.

PMID- 11300752
TI  - Measurement of the radiological hip joint space width. An evaluation of various
      methods of measurement.
AB  - OBJECTIVE: To determine the most relevant method of measurement of the
      radiographic hip joint space width (JSW). DESIGN: Seventy hips were examined from
      36 patients of the ECHODIAH study having had one to four X-rays of the pelvis
      during the 3-year course of the study. Minimum interbone distance (MIDc), mean
      width of both the whole joint space (MJSWL) and a region of interest of the joint
      space (MJSWroi) were measured using computerized analysis of digitized
      radiographs. MID was also measured using a graduated eyepiece (MIDge).
      Reproducibility of the measurement was assessed by the intraclass coefficient of
      correlation. Sensitivity to change was evaluated by the standardized response
      mean. RESULTS: The intraobserver intraclass coefficient of correlation of MIDc
      and MJSWroi was 0.98 and 0.94, respectively. The mean value degrees S.D. of
      MJSWL, MJSWroi, MIDc and MIDge was 3.3 degrees 0.9, 2.6 degrees 0.9, 2.4 degrees
      0.9 and 2.6 degrees 1.2 mm, respectively. MIDge was significantly larger than
      MIDc (mean difference: 0.21 degrees 0.62 mm, P<0.001), in both normal and
      osteoarthritic hips. However, the difference between MIDge and MIDc varied
      largely when considering topography of femoral head migration. Whatever the
      method was, a significant (P<0.001) mean decrease of nearly 0.5 mm was found in
      osteoarthritic hips over the 3 year follow-up. The standardized response mean for
      MJSWL, MJSWroi, MIDge and MIDc was 0.73, 0.75, 0.79 and 0.85, respectively.
      Superiority of MIDc, in term of sensitivity to change, was mainly seen in
      osteoarthritic hips showing a superomedial or a concentric migration of the
      femoral head. CONCLUSION: Minimum interbone distance measured with a computer
      assisted method is suggested as the most suitable method for the evaluation of
      hip osteoarthritis (OA) progression.

PMID- 11300753
TI  - Re: Pavelka K, Gatterova J, Gallerova V, Urbanova Z, Sedlackova M, Altman R. A 5
      year randomized controlled double-bling study of glycosaminoglycan polysulfuric
      acid complex (Rumalon) as a structure-modifying therapy in osteoarthritis of the
      hip and knee. Oseoarthritis Cart 2000;8:335-342.

PMID- 11300755
TI  - Prion glycoprotein: structure, dynamics, and roles for the sugars.
AB  - The prion protein contains two N-linked glycosylation sites and a
      glycosylphosphatidylinositol (GPI) anchor. The large size of the N-linked sugars,
      together with their dynamic properties, enables them to shield two orthogonal
      faces of the protein almost completely. Thus, the sugars can protect large
      regions of the protein surface from proteases and from nonspecific protein
      protein interactions. Immunoprecipitation of prion protein with calnexin suggests
      that in the ER the oligosaccharides may provide a route for protein folding via
      the calnexin pathway. Major questions relate to the relevance of the glycoform
      distribution (as defined by glycan site occupancy) to strain type and disease
      transmission. Glycan analysis has shown that prion protein contains at least 52
      different sugars, that these consist of a subset of brain sugars, and that there
      is site specific glycan processing. PrP(Sc) from the brains of Syrian hamsters
      contains the same set of glycans as PrP(C), but a higher proportion of tri- and
      tetra-antennary sugars. This may be attributed to a decrease in the activity of
      GnTIII. The GPI anchor, which is modified with sialic acid, may allow the prion
      protein to be mobile in the lipid bilayer. Potentially, this provides a possible
      means for translocating the prions from one cell to another.

PMID- 11300756
TI  - Dynamics of protein ligand binding on multiple time scales: NADH binding to
      lactate dehydrogenase.
AB  - Although the importance of atomic motion to how proteins function has been
      conjectured for several decades, the characterization of protein dynamics on
      multiple time scales is scant. This is because of severe experimental and
      theoretical difficulties, particularly characterizing the nanosecond to
      millisecond time scales. Here, we apply advanced laser-induced temperature-jump
      relaxation spectroscopic techniques to examine the kinetics of NADH binding to
      lactate dehydrogenase over this time scale. The bimolecular rate process, at
      about 290 micros, is easily observed as are multiple faster events (with
      relaxation times of 200 ns, 3.5 micros, and 24 micros), revealing a rich
      dynamical nature of the binding step. The results show that there are multiple
      structures of bound enzyme-ligand complexes, some of which are likely to be far
      from the catalytically productive structure. The results have important
      implications for interpretations of the binding thermodynamics of ligands to LDH
      and, by extension, to other proteins. The observed processes likely play a role
      in the dynamics of the chemistry that is catalyzed by lactate dehydrogenase.

PMID- 11300757
TI  - Analysis of enzyme kinetics using electrospray ionization mass spectrometry and
      multiple reaction monitoring: fucosyltransferase V.
AB  - An accurate, rapid, and versatile method for the analysis of enzyme kinetics
      using electrospray ionization mass spectrometry (ESI-MS) has been developed and
      demonstrated using fucosyltransferase V. Reactions performed in primary or
      secondary amine-containing buffers were diluted in an ESI solvent and directly
      analyzed without purification of the reaction products. Decreased mass resolution
      was used to maximize instrument sensitivity, and multiple reaction monitoring
      (MRM), in the tandem mass spectrometric mode, was used to enhance selectivity of
      detection. The approach allowed simultaneous monitoring of multiple processes,
      including substrate consumption, product formation, and the intensity of an
      internal standard. MRM gave an apparent K(m) for GDP-L-fucose (GDP-Fuc) of 50.4
      +/- 5.5 microM and a k(cat) of 1.46 +/- 0.044 s(-1). Under the same conditions,
      the conventional radioactivity-based assay using GDP-[U-(14)C]Fuc as substrate
      gave virtually identical results: K(m) = 54.3 +/- 4.6 microM and k(cat) = 1.49 +/
      0.039 s(-1). The close correlation of the data showed that ESI-MS coupled to MRM
      is a valid approach for the analysis of enzyme kinetics. Consequently, this
      method represents a valuable alternative to existing analytic methods because of
      the option of simultaneously monitoring multiple species, the high degree of
      specificity, and rapid analysis times and because it does not rely on the
      availability of radioactive or chromogenic substrates.

PMID- 11300758
TI  - Distal ligand reactivity and quaternary structure studies of proximally detached
      hemoglobins.
AB  - The linkage between the proximal histidines and the proximal polypeptide in
      normal adult human hemoglobin (Hb A) has been proposed to play a major role in
      transmitting allosteric effects between oxygen binding sites [Perutz, M. F.
      (1970) Nature 228, 726-734]. Here we present circular dichroism (CD), (1)H NMR,
      analytical ultracentrifugation, and stopped-flow kinetic data to better define
      the quaternary structure of hemoglobins in which the linkage between the proximal
      histidines and the polypeptide backbone has been broken [Barrick et al. Nat.
      Struct. Biol. 4, 78-83 (1997)] and to characterize the distal ligand binding
      properties of these proximally detached Hbs. CD spectroscopy indicates that rHb
      (alphaH87G) and rHb (alphaH87G/betaH92G) retain at least partial T-quaternary
      structure with distal ligand bound, whereas rHb (betaH92G) does not, consistent
      with (1)H NMR spectra. Analytical ultracentrifugation reveals significant
      tetramer dissociation in rHb (betaH92G) to be the likely cause of loss of T-state
      markers. These quaternary structure studies indicate that in distally liganded
      Hb, the T-state is compatible with proximal linkages in the beta- but not the
      alpha-chains. (1)H NMR titrations of rHb (alphaH87G) with n-butyl isocyanide
      demonstrate the alpha-chains to be of high affinity as compared with the beta
      chains. Comparing ligand association and dissociation rates between the rHb
      (alphaH87G) variant with the T- and R-states of wild-type Hb A indicates that at
      the alpha-chains, carbon monoxide affinity is modulated entirely by the proximal
      linkage, rather than from distal interactions. Some residual allosteric
      interactions may remain operative at the beta-chains of rHb (alphaH87G).

PMID- 11300759
TI  - The power stroke causes changes in the orientation and mobility of the termini of
      essential light chain 1 of myosin.
AB  - Binding of ATP to the catalytic domain of myosin induces a local conformational
      change which is believed to cause a major rotation of an 8.5 nm alpha-helix that
      is stabilized by the regulatory and essential light chains. Here we attempt to
      follow this rotation by measuring the mobility and orientation of a fluorescent
      probe attached near the C- or N-terminus of essential light chain 1 (LC1).
      Cysteine 178 of wild-type LC1, or Cys engineered near the N-terminus of mutant
      LC1, was labeled with tetramethylrhodamine and exchanged into skeletal
      subfragment-1 (S1) or into striated muscle fibers. In the absence of ATP, the
      fluorescence anisotropy (r) and the rotational correlation time (rho) of S1
      reconstituted with LC1 labeled near the C-terminus were 0.195 and 66.6 ns,
      respectively. In the presence of ATP, r and rho increased to 0.233 and 233 ns,
      indicating considerable immobilization of the probe. A related parameter
      indicating the degree of order of cross-bridges in muscle fibers, Deltar, was
      small in rigor fibers (-0.009) and increased in relaxed fibers (0.030). For S1
      reconstituted with LC1 labeled near the N-terminus, the steady-state anisotropy
      was 0.168 in rigor, and increased to 0.223 in relaxed state. In fibers, the
      difference in rigor was large (Deltar = 0.080), because of binding to the thin
      filaments, and decreased to 0.037 in relaxed fibers. These results suggest that
      before the power stroke, in the presence of ATP or its products of hydrolysis,
      the termini of LC1 are immobilized and ordered, and after the stroke, they become
      more mobile and partially disordered. The results are consistent with
      crystallographic structures that show that the level of putative stabilizing
      interactions of LC1 with the heavy chain of S1 in the transition state is reduced
      as the regulatory domain rotates to its post-power stroke position.

PMID- 11300760
TI  - Intermolecular interactions between cholecystokinin-8 and the third extracellular
      loop of the cholecystokinin A receptor.
AB  - The interaction of the C-terminal octapeptide of cholecystokinin, CCK-8, with the
      third extracellular loop of human cholecystokinin-A receptor, CCK(A)-R(329-357),
      has been probed by high-resolution NMR and extensive computer simulations. The
      structure of CCK(A)-R(329-357) in the presence of dodecylphosphocholine micelles
      consists of three alpha-helices, with the first and third corresponding to the
      extracellular ends of transmembrane (TM) helices 6 and 7. The central helix,
      residues W335-R345, is found to lie on the zwitterionic surface. Titration with
      CCK-8 produces a stable complex with a number of intermolecular NOEs between the
      C-terminus of the ligand (Trp(30), Met(31), Asp(32)) and the interface of TM6 and
      the third extracellular loop (N333, A334, Y338) of the receptor fragment. The
      mode of ligand binding based on these intermolecular NOEs is in agreement with a
      number of published findings from receptor mutagenesis and photoaffinity cross
      linking. Utilizing these ligand/receptor points of interaction, the structural
      features of CCK(A)-R(329-357), and also the structures of CCK-8 and CCK(A)-R(1
      47) previously determined, extensive molecular dynamics simulations of the CCK
      8/CCK(A)-R complex were carried out. The results provide unique insight into the
      molecular interactions and forces important for the binding of CCK-8 to CCK(A)-R.

PMID- 11300761
TI  - The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment.
AB  - Human beta-defensin-2 (HBD-2) is a member of the defensin family of antimicrobial
      peptides. HBD-2 was first isolated from inflamed skin where it is posited to
      participate in the killing of invasive bacteria and in the recruitment of cells
      of the adaptive immune response. Static light scattering and two-dimensional
      proton nuclear magnetic resonance spectroscopy have been used to assess the
      physical state and structure of HBD-2 in solution. At concentrations of < or =
      2.4 mM, HBD-2 is monomeric. The structure is amphiphilic with a nonuniform
      surface distribution of positive charge and contains several key structural
      elements, including a triple-stranded, antiparallel beta-sheet with strands 2 and
      3 in a beta-hairpin conformation. A beta-bulge in the second strand occurs at
      Gly28, a position conserved in the entire defensin family. In solution, HBD-2
      exhibits an alpha-helical segment near the N-terminus that has not been
      previously ascribed to solution structures of alpha-defensins or to the beta
      defensin BNBD-12. This novel structural element may be a factor contributing to
      the specific microbicidal or chemokine-like properties of HBD-2.

PMID- 11300762
TI  - Thermodynamics of denaturation of hisactophilin, a beta-trefoil protein.
AB  - Hisactophilin is a histidine-rich pH-dependent actin-binding protein from
      Dictyostelium discoideum. The structure of hisactophilin is typical of the beta
      trefoil fold, a common structure adopted by diverse proteins with unrelated
      primary sequences and functions. The thermodynamics of denaturation of
      hisactophilin have been measured using fluorescence- and CD-monitored equilibrium
      urea denaturation curves, pH-denaturation, and thermal denaturation curves, as
      well as differential scanning calorimetry. Urea denaturation is reversible from
      pH 5.7 to pH 9.7; however, thermal denaturation is highly reversible only below
      pH approximately 6.2. Reversible denaturation by urea and heat is well fit using
      a two-state transition between the native and the denatured states. Urea
      denaturation curves are best fit using a quadratic dependence of the Gibbs free
      energy of unfolding upon urea concentration. Hisactophilin has moderate, roughly
      constant stability from pH 7.7 to pH 9.7; however, below pH 7.7, stability
      decreases markedly, most likely due to protonation of histidine residues.
      Enthalpic effects of histidine ionization upon unfolding also appear to be
      involved in the occurrence of cold unfolding of hisactophilin under relatively
      mild solution conditions. The stability data for hisactophilin are compared with
      data on hisactophilin function, and with data for two other beta-trefoil
      proteins, human interleukin-1beta, and basic fibroblast growth factor.

PMID- 11300763
TI  - Molecular motion of spin labeled side chains in alpha-helices: analysis by
      variation of side chain structure.
AB  - Two single cysteine substitution mutants at helix surface sites in T4 lysozyme
      (D72C and V131C) have been modified with a series of nitroxide
      methanethiosulfonate reagents to investigate the structural and dynamical origins
      of their electron paramagnetic resonance spectra. The novel reagents include 4
      substituted derivatives of either the pyrroline or pyrrolidine series of
      nitroxides. The spectral line shapes were analyzed as a function of side chain
      structure and temperature using a simulation method with a single order parameter
      and diffusion rates about three orthogonal axes as parameters. Taken together,
      the results provide strong support for an anisotropic motional model of the side
      chain, which was previously proposed from qualitative features of the spectra and
      crystal structures of spin labeled T4 lysozyme. Site-specific differences in
      apparent order parameter are interpreted in terms of backbone dynamics modes with
      characteristic correlation times in the nanosecond or faster time scale. The
      saturated 4-substituted pyrrolidine nitroxides are shown to be a suitable
      template for novel "functionalized" side chains designed to mimic salient
      features of the native side chains they replace.

PMID- 11300764
TI  - Protein-DNA binding correlates with structural thermostability for the full
      length human p53 protein.
AB  - Full-length p53 protein purified from Escherichia coli in the unmodified,
      "latent" form was examined by several methods to correlate thermal stability of
      structure with functional DNA binding. Structure prediction algorithms indicate
      that the majority of beta-sheet structure occurs in the p53 core DNA binding
      domain. Circular dichroism spectra demonstrate that the intact protein is
      surprisingly stable with a midpoint for the irreversible unfolding transition at
      approximately 73 degrees C. Significant beta-sheet structural signal remains even
      to 100 degrees C. The persistent beta-sheet CD signal correlates with significant
      DNA binding (K(d) approximately nM range) to temperatures as high as 50 degrees
      C. These data confirm the ability of the DNA binding domain in the full-length
      "latent" protein to bind consensus dsDNA targets effectively in the absence of
      activators over a broad temperature range. In addition, we demonstrate that
      Ab1620 reactivity is not directly correlated with the functional activity of the
      full-length protein since loss of this epitope occurs at temperatures at which
      significant specific DNA binding can still be measured.

PMID- 11300765
TI  - 15-mer DNA duplexes containing an abasic site are thermodynamically more stable
      with adjacent purines than with pyrimidines.
AB  - Abasic site (AP)-containing duplexes, with flanking adenine (A) or cytosine (C)
      bases, were shown to be more stable with flanking A than with C bases [Sagi, J.,
      Hang, B., and Singer, B. (1999) Chem. Res. Toxicol. 12, 917-923]. We investigated
      whether the lower-magnitude destabilization by an AP site, with A neighbors, is a
      general effect of the purine versus the pyrimidine neighbors. Duplex stability,
      as compared to that of the corresponding control duplexes, was markedly decreased
      by the incorporation of the AP site (x) opposite any of the four bases. However,
      for the duplexes containing T, A, or C opposite the AP site, replacement of the
      symmetric doublet flanking pyrimidine bases with purines resulted in a smaller
      destabilization effect. The average stabilizing effect of the symmetric doublet
      purine neighbors of an AP site opposite T, A, or C bases was 3.2 degrees C
      (DeltaT(m)) and 1.3 kcal/mol (DeltaDeltaG degrees (37)) compared to those of
      pyrimidine neighbors. In contrast, a G.AP pair reduced or eliminated the
      differential effect of the neighbors. Using unrestrained molecular dynamics, it
      was shown that for the duplexes containing T opposite the AP site, with doublet
      pyrimidine neighbors, there was a larger magnitude of curvature around the lesion
      site than for the duplexes with the purines flanking the AP site. Purines
      flanking the AP site tend to shift toward each other, creating overlap, in
      contrast to the flanking pyrimidines. This indicates the possibility of stacking
      between purine bases at the AP site and can be the reason for the observed
      smaller thermodynamic destabilization of the duplexes with the AAxAA and GGxGG
      central sequences, as compared to those with TTxTT and CCxCC sequences. This work
      showed that for an AP site the GC content is not the only determinant of duplex
      stability, but rather is influenced more by whether purines or pyrimidines flank
      the AP site.

PMID- 11300766
TI  - Isolation and characterization of the UGT2B28 cDNA encoding a novel human steroid
      conjugating UDP-glucuronosyltransferase.
AB  - UDP-glucuronosyltransferase (UGT) enzymes belonging to the UGT2B subfamily
      catalyze the transfer of glucuronic acid to a large number of endogenous
      compounds, particularly steroids, to facilitate their elimination from target
      cells. A novel human UGT2B cDNA of 1666 bp was isolated and encodes a 529-amino
      acid protein named UGT2B28 type I. Glucuronidation assays demonstrated that
      UGT2B28 type I catalyzes the conjugation of endogenous and exogenous compounds.
      The tissue distribution of UGT2B28 revealed the expression of the type I
      transcript in the liver, breast, and LNCaP cells. Two other UGT2B cDNAs were
      isolated, and sequence analysis led to the identification of two truncated
      UGT2B28 species. UGT2B28 type II differs from type I by a deletion of 308 bp in
      the cofactor binding domain, whereas UGT2B28 type III lacks 351 bp in the
      putative substrate binding domain. All UGT2B28 isoforms are encoded by a single
      UGT2B28 gene which has a genomic organization similar to that of the other UGT2B
      genes characterized thus far. Although no substrates could be identified for the
      shorter isoforms, the three subtypes were shown to be located in the endoplasmic
      reticulum and the perinuclear membrane, demonstrating that the missing domains
      are not required for the subcellular localization of these UGT2B proteins.
      However, all the domains remain necessary for observing glucuronidation activity.
      The expression of UGT2B28 type I in the breast and liver suggests a role of this
      enzyme in the androgen and estrogen metabolism in these tissues.

PMID- 11300767
TI  - The T7 RNA polymerase intercalating hairpin is important for promoter opening
      during initiation but not for RNA displacement or transcription bubble stability
      during elongation.
AB  - The recently described crystal structures of a T7RNAP-promoter complex and an
      initial transcription complex reveal a beta-hairpin which inserts between the
      template and nontemplate strands of the promoter [Cheetham, G. M., et al. (1999)
      Nature 399, 80; Cheetham, G. M., et al. (1999) Science 286, 2305]. A stacking
      interaction between the exposed DNA bases and a valine at the tip of this hairpin
      may be especially important for stabilizing the opened promoter during
      initiation. It has been suggested that this hairpin may also be important for
      holding the transcription bubble open during transcript elongation, and a
      proposed model for how the RNA exits the transcription complex implies that this
      hairpin may also help displace the RNA from the template strand. To test these
      hypotheses, we have characterized both point and deletion mutants of this
      element. We find that these mutants exhibit reduced activity on linear, double
      stranded templates but not on supercoiled or partially single-stranded templates.
      Probing of promoter-polymerase complexes, initial transcription complexes, and
      elongation complexes with KMnO(4) and a single-strand specific endonuclease
      reveals that the mutants have greatly reduced promoter unwinding activity during
      initiation. However, the structure and stability of the transcription bubble
      during elongation are not altered in the mutant enzymes, and RNA displacement
      activity is also normal. Thus, the T7RNAP intercalating hairpin is important,
      though not essential, for stabilizing the opened promoter during initiation, but
      is not important for RNA displacement or for transcription bubble structure or
      stability during elongation.

PMID- 11300768
TI  - Protein dynamics control proton transfers to the substrate on the His72Asn mutant
      of p-hydroxybenzoate hydroxylase.
AB  - p-Hydroxybenzoate hydroxylase (PHBH) hydroxylates activated benzoates using NADPH
      as a reductant and O(2) as an oxygenating substrate. Because the flavin, when
      reduced, will quickly react with oxygen in either the presence or absence of a
      phenolic substrate, it is important to regulate flavin reduction to prevent the
      uncontrolled reaction of NADPH and oxygen to form H(2)O(2). Reduction is
      controlled by the protonation state of the aromatic substrate p-hydroxybenzoate
      (pOHB), which when ionized to the phenolate facilitates the movement of flavin
      between two conformations, termed "in" and "out". When the hydrogen bond network
      that provides communication between the substrate and solvent is disrupted by
      changing its terminal residue, His72, to Asn, protons from solution no longer
      equilibrate rapidly with pOHB bound to the active site [Palfey, B. A., Moran, G.
      R., Entsch, B., Ballou, D. P., and Massey, V. (1999) Biochemistry 38, 1153-1158].
      Thus, one population of the His72Asn enzyme reduces rapidly and has the phenolate
      form of pOHB bound at the active site and the flavin in the out conformation. The
      remaining population of the His72Asn enzyme reduces slowly and has the phenolic
      form of pOHB bound and the flavin in the in conformation. We have investigated
      the mechanisms of proton transfer between solvent and pOHB bound to the His72Asn
      form of the enzyme by double-mixing and single-mixing stopped-flow experiments.
      We find that, depending on the initial ionization state of bound pOHB and the new
      pH of the solution, the ionization/protonation of pOHB proceeds through the
      direct reaction of hydronium or hydroxide with the enzyme-ligand complex and
      leads to the conversion of one flavin conformation to the other. Our kinetic data
      indicate that the enzyme with the flavin in the in conformation reacts in two
      steps. Inspection of crystal structures suggests that the hydroxide ion would
      react at the re-face of the flavin, and its reaction with pOHB is limited by the
      movement of Pro293, a conserved residue in similar flavoprotein hydroxylases. We
      hypothesize that this type of breathing mode by the protein may have been used to
      compensate for the lack of an efficient proton-transfer network in ancestral
      hydroxylases, permitting useful catalysis prior to the emergence of specialized
      proton-transfer mechanisms.

PMID- 11300769
TI  - Structure of intact AhpF reveals a mirrored thioredoxin-like active site and
      implies large domain rotations during catalysis.
AB  - AhpF, a homodimer of 57 kDa subunits, is a flavoenzyme which catalyzes the NADH
      dependent reduction of redox-active disulfide bonds in the peroxidase AhpC, a
      member of the recently identified peroxiredoxin class of antioxidant enzymes. The
      structure of AhpF from Salmonella typhimurium at 2.0 A resolution, determined
      using multiwavelength anomalous dispersion, shows that the C-terminal portion of
      AhpF (residues 210-521) is structurally like Escherichia coli thioredoxin
      reductase. In addition, AhpF has an N-terminal domain (residues 1-196) formed
      from two contiguous thioredoxin folds, but containing just a single redox-active
      disulfide (Cys129-Cys132). A flexible linker (residues 197-209) connects the
      domains, consistent with experiments showing that the N-terminal domain acts as
      an appended substrate, first being reduced by the C-terminal portion of AhpF, and
      subsequently reducing AhpC. Modeling studies imply that an intrasubunit electron
      transfer accounts for the reduction of the N-terminal domain in dimeric AhpF.
      Furthermore, comparing the N-terminal domain with protein disulfide
      oxidoreductase from Pyrococcus furiosis, we describe a new class of protein
      disulfide oxidoreductases based on a novel mirror-image active site arrangement,
      with a distinct carboxylate (Glu86) being functionally equivalent to the key acid
      (Asp26) of E. coli thioredoxin. A final fortuitous result is that the N-terminal
      redox center is reduced and provides a high-resolution view of the thiol-thiolate
      hydrogen bond that has been predicted to stabilize the attacking thiolate in
      thioredoxin-like proteins.

PMID- 11300770
TI  - Activity of one of two engineered heterodimers of AhpF, the NADH:peroxiredoxin
      oxidoreductase from Salmonella typhimurium, reveals intrasubunit electron
      transfer between domains.
AB  - AhpF, the flavoprotein reductase component of the Salmonella typhimurium alkyl
      hydroperoxide reductase system, catalyzes the reduction of an intersubunit
      disulfide bond in the peroxidatic active site of the system's other component,
      AhpC, a member of the peroxiredoxin family. Previous studies have shown that AhpF
      can be dissected into two functional units, a thioredoxin reductase-like C
      terminus (containing FAD and a redox-active disulfide, Cys345-Cys348) and an N
      terminal domain containing a second redox-active disulfide center (Cys129
      Cys132). The role of the N-terminal domain as the direct reductant of AhpC,
      mediating electron transfer from the C-terminal redox centers of AhpF, has been
      firmly established by several approaches. Not known, however, was whether the
      transfer of electrons between the C-terminal and N-terminal disulfide centers
      occurred as an inter- or intrasubunit process in dimeric AhpF. Two heterodimeric
      AhpF species were therefore created in which one of the two pathways was
      completely disrupted while the other was left partially intact in each construct.
      Only the heterodimer containing one monomer of wild type AhpF and a monomer of
      mutated (and truncated) AhpF exhibited peroxidase activity with AhpC indicating
      that electron transfer between domains of AhpF is an intrasubunit process.

PMID- 11300771
TI  - Stereochemical analysis of the reaction catalyzed by human protein geranylgeranyl
      transferase.
AB  - Protein geranylgeranyltransferase type I (PGGTase-I) catalyzes the nucleophilic
      substitution reaction between the C(20) geranylgeranyl diphosphate (GGPP) and a
      protein-derived thiol to form a thioether linkage. Here, we describe the
      stereochemical outcome, at the isoprenoid C1, of the reaction catalyzed by human
      PGGTase-I. To accomplish this, the pentapeptide N-dansyl-GCVLL was first
      enzymatically prenylated by human PGGTase-I with either (S)-[1-(2)H]farnesyl
      diphosphate or (S)-[1-(2)H]GGPP. The prenylated products were then degraded to
      dipeptides using carboxypeptidase Y. After HPLC purification, the prenylated
      dipeptide products were analyzed by (1)H NMR spectroscopy. The final spectra were
      compared with the spectra from the same product obtained via chemical synthesis
      to deduce the stereochemistry of the PGGTase-I-catalyzed reaction. This
      comparison showed that the reaction proceeds with inversion of configuration with
      no detectable (< 6%) racemization. These results are more consistent with an
      associative-type mechanism, but they cannot be used to rule out a dissociative
      mechanism involving a rigid, solvent-sequestered, tight ion pair.

PMID- 11300772
TI  - Evidence for an essential histidine residue in the ascorbate-binding site of
      cytochrome b561.
AB  - Cytochrome b(561) mediates equilibration of the ascorbate/semidehydroascorbate
      redox couple across the membranes of secretory vesicles. The cytochrome is
      reduced by ascorbic acid and oxidized by semidehydroascorbate on either side of
      the membrane. Treatment with diethyl pyrocarbonate (DEPC) inhibits reduction of
      the cytochrome by ascorbate, but this activity can be restored by subsequent
      treatment with hydroxylamine, suggesting the involvement of an essential
      histidine residue. Moreover, DEPC inactivates cytochrome b(561) more rapidly at
      alkaline pH, consistent with modification of a histidine residue. DEPC does not
      affect the absorption spectrum of cytochrome b(561) nor does it change the
      midpoint reduction potential, confirming that histidine modification does not
      affect the heme. Ascorbate protects the cytochrome from inactivation by DEPC,
      indicating that the essential histidine is in the ascorbate-binding site. Further
      evidence for this is that DEPC treatment inhibits oxidation of the cytochrome by
      semidehydroascorbate but not by ferricyanide. This supports a reaction mechanism
      in which ascorbate loses a hydrogen atom by donating a proton to histidine and
      transferring an electron to the heme.

PMID- 11300773
TI  - Reaction path of phosphofructo-1-kinase is altered by mutagenesis and alternative
      substrates.
AB  - Escherichia coli phosphofructokinase (PFK) has been proposed to have a random,
      nonrapid equilibrium mechanism that produces nonallosteric ATP inhibition as a
      result of substrate antagonism. The consequences of such a mechanism have been
      investigated by employing alternative substrates and mutants of the enzyme that
      produce a variety of nonallosteric kinetic patterns demonstrating substrate
      inhibition and sigmoid velocity curves. Mutations of a methionine residue in the
      sugar phosphate binding site produced apparent cooperativity in the interaction
      of fructose 6-phosphate. Cooperativity could also be seen with native enzyme
      using a poorly binding substrate, fructose 1-phosphate. With an alternative
      nucleotide, 1-carboxymethyl-ATP, coupled with a mutation that introduced a
      negative charge in the nucleotide binding site, one could observe substrate
      inhibition by fructose 6-phosphate and apparent cooperativity in the interaction
      with nucleotide. Furthermore, the use of a phosphoryl donor, gamma-thiol-ATP,
      which greatly reduced the catalytic rate, apparently facilitated the
      equilibration of all binding reactions and eliminated ATP inhibition. These
      unusual kinetic patterns could be interpreted within the random, steady-state
      model as reflecting changes in the rates of particular binding and catalytic
      events.

PMID- 11300774
TI  - Site-directed mutagenesis of human nucleoside triphosphate diphosphohydrolase 3:
      the importance of residues in the apyrase conserved regions.
AB  - Ecto-nucleoside triphosphate diphosphohydrolase 3 (eNTPDase-3, also known as HB6
      and CD39L3) is a membrane-associated ecto-apyrase. Only a few functionally
      significant residues have been elucidated for this enzyme, as well as for the
      whole family of eNTPDase enzymes. Four highly conserved regions (apyrase
      conserved regions, ACRs) have been identified in all the members of eNTPDase
      family, suggesting their importance for biological activity. In an effort to
      identify those amino acids important for the catalytic activity of the eNTPDase
      family, as well as those residues mediating substrate specificity, 11 point
      mutations of 7 amino acid residues in ACR1-4 of eNTPDase-3 were constructed by
      site-directed mutagenesis. Mutagenesis of asparagine 191 to alanine (N191A),
      glutamine 226 to alanine (Q226A), and arginine 67 to glycine (R67G) resulted in
      an increase in the rates of hydrolysis of nucleoside diphosphates relative to
      triphosphates. Mutagenesis of arginine 146 to proline (R146P) essentially
      converted the eNTPDase-3 ecto-apyrase to an ecto-ATPase (eNTPDase-2), mainly by
      decreasing the hydrolysis rates for nucleoside diphosphates. The Q226A mutant
      exhibited a change in the divalent cation requirement for nucleotidase activity
      relative to the wild-type and the other mutants. Mutation of glutamate 182 to
      aspartate (E182D) or glutamine (E182Q), and mutation of serine 224 to alanine
      (S224A) completely abolished enzymatic activity. We conclude that the residues
      corresponding to eNTPDase-3 glutamate 182 in ACR3 and serine 224 in ACR4 are
      essential for the enzymatic activity of eNTPDases in general, and that arginine
      67, arginine 146, asparagine 191, and glutamine 226 are important for determining
      substrate specificity for human ecto-nucleoside triphosphate diphosphohydrolase
      3.

PMID- 11300775
TI  - Shikimate-3-phosphate binds to the isolated N-terminal domain of 5
      enolpyruvylshikimate-3-phosphate synthase.
AB  - 5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase catalyzes the transfer of the
      enolpyruvyl moiety from phosphoenolpyruvate (PEP) to shikimate-3-phosphate (S3P).
      Mutagenesis and X-ray crystallography data suggest that the active site of the
      enzyme is in the cleft between its two globular domains; however, they have not
      defined which residues are responsible for substrate binding and catalysis. Here
      we attempt to establish the binding of the substrate S3P to the isolated N
      terminal domain of EPSP synthase using a combination of NMR spectroscopy and
      isothermal titration calorimetry. Our experimental results indicate that there is
      a saturable and stable conformational change in the isolated N-terminal domain
      upon S3P binding and that the chemical environment of the S3P phosphorus when
      bound to the isolated domain is very similar to that of S3P bound to EPSP
      synthase. We also conclude that most of the free energy of S3P binding to EPSP
      synthase is contributed by the N-terminal domain.

PMID- 11300776
TI  - Characterization of the denatured states distribution of neocarzinostatin by
      small-angle neutron scattering and differential scanning calorimetry.
AB  - The denatured states of a small globular protein, apo-neocarzinostatin (NCS),
      have been characterized using several techniques. Structural properties were
      investigated by optical spectroscopy techniques and small-angle neutron
      scattering (SANS), as a function of guanidinium chloride (GdmCl) concentration.
      SANS experiments show that in heavy water, the protein keeps its native size at
      GdmCl concentrations below 2.5 M. A sharp transition occurs at about 3.6 M GdmCl,
      and NCS behaves like an excluded volume chain above 5 M. The same behavior is
      observed in deuterated buffer by fluorescence and circular dichroism
      measurements. For the H(2)O buffer, the transition occurs with lower
      concentration of denaturant, the shift being about 0.6 M. 8-Anilino-1
      naphthalenesulfonate (ANS) was used as a hydrophobic fluorescent probe for
      studying the early stages of protein unfolding. Protein denaturation modifies the
      fluorescence intensity of ANS, a maximum of intensity being detected close to 2 M
      GdmCl in hydrogenated buffer, which shows the existence of at least one
      intermediate state populated at the beginning of the unfolding pathway.
      Differential scanning calorimetry (DSC) was used to obtain thermodynamic values
      for NCS denaturation. The melting curves recorded between 20 and 90 degrees C in
      the presence of various GdmCl concentrations (0-3 M) cannot be explained by a
      simple two-state model. Altogether, the data presented in this paper suggest that
      before unfolding the protein explores a distribution of states which is centered
      around compact states at denaturant concentrations below 2 M in H(2)O, and then
      shifts to less structured states by increasing denaturant concentrations.

PMID- 11300777
TI  - 15N NMR relaxation studies of backbone dynamics in free and steroid-bound Delta 5
      3-ketosteroid isomerase from Pseudomonas testosteroni.
AB  - The backbone dynamics of Delta(5)-3-ketosteroid isomerase (KSI) from Pseudomonas
      testosteroni has been studied in free enzyme and its complex with a steroid
      ligand, 19-nortestosterone hemisuccinate (19-NTHS), by (15)N relaxation
      measurements. The relaxation data were analyzed using the model-free formalism to
      extract the model-free parameters (S(2), tau(e), and R(ex)) and the overall
      rotational correlation time (tau(m)). The rotational correlation times were 19.23
      +/- 0.08 and 17.08 +/- 0.07 ns with the diffusion anisotropies (D( parallel)/D(
      perpendicular)) of 1.26 +/- 0.03 and 1.25 +/- 0.03 for the free and steroid-bound
      KSI, respectively. The binding of 19-NTHS to free KSI causes a slight increase in
      the order parameters (S(2)) for a number of residues, which are located mainly in
      helix A1 and strand B4. However, the majority of the residues exhibit reduced
      order parameters upon ligand binding. In particular, strands B3, B5, and B6,
      which have most of the residues involved in the dimer interaction, have the
      reduced order parameters in the steroid-bound KSI, indicating the increased high
      frequency (pico- to nanosecond) motions in the intersubunit region of this
      homodimeric enzyme. Our results differ from those of previous studies on the
      backbone dynamics of monomeric proteins, in which high-frequency internal motions
      are typically restricted upon ligand binding.

PMID- 11300778
TI  - Free energies of urea and of thermal unfolding show that two tandem repeats of
      spectrin are thermodynamically more stable than a single repeat.
AB  - Free energies of both urea and thermal denaturation have been measured for three
      pairs of one- and two-repeat fragments, cloned in tandem from the cytoskeletal
      protein, alpha-spectrin, from chicken brain to ascertain whether one- and two
      repeat fragments are equally stable. One- and two-repeat fragments of each pair
      were designed with the same N-terminus, whereas the C-terminus of the two-repeat
      fragment was 106 residues or the length of one repeat downstream from that of the
      one-repeat fragment. The averaged free energies of urea and thermal denaturation
      of the paired fragments, (R16)(00) and (R16R17)(00), (R16)(0+3) and
      (R16R17)(0+3), and (R16)(+8-4) and (R16R17)(+8-4) [subscripts represent the N-
      and C-terminal positions with "00" referring to the N- and C-termini defining a
      repeat according to X-ray crystal structures of two repeat fragments [Grum, V.
      L., Li, D., MacDonald, R. I., and Mondragon, A. (1999) Cell 98, 523-535] and "+"
      and "-" referring to positions upstream and downstream therefrom, respectively],
      increased from 3.7 +/- 0.4 kcal/mol for (R16)(00), 3.7 +/- 0.5 kcal/mol for
      (R16)(0+3), 4.4 +/- 0.4 kcal/mol for (R16)(+8-4), 6.2 +/- 0.6 kcal/mol for
      (R16R17)(+8-4), 8.3 +/- 0.4 kcal/mol for (R16R17)(00) to 9.9 +/- 1.0 kcal/mol for
      (R16R17)(0+3). Thus, the two-repeat fragment of each pair was significantly more
      thermodynamically stable than the single repeat by both urea and thermal
      denaturation. Differences in phasing among single repeats did not have the same
      effect as the same differences in phasing among two-repeat fragments. Addition of
      nine residues to the C-terminus of (R16R17)(00) yielded a free energy of
      unfolding of 7.9 +/- 0.8 kcal/mol, whereas addition of seven residues to the C
      terminus of (R16)(+8-4) yielded a free energy of unfolding of 5.9 +/- 0.3
      kcal/mol.

PMID- 11300779
TI  - Backbone dynamics of receptor binding and antigenic regions of a Pseudomonas
      aeruginosa pilin monomer.
AB  - Pilin is the major structural protein that forms type IV pili of various
      pathogenic bacteria, including Pseudomonas aeruginosa. Pilin is involved in
      attachment of the bacterium to host cells during infection, in the initiation of
      immune response, and serves as a receptor for a variety of bacteriophage. We have
      used (15)N nuclear magnetic resonance relaxation measurements to probe the
      backbone dynamics of an N-terminally truncated monomeric pilin from P. aeruginosa
      strain K122-4. (15)N-T(1), -T(2), and [(1)H]-(15)N nuclear Overhauser enhancement
      measurements were carried out at three magnetic field strengths. The measurements
      were interpreted using the Lipari-Szabo model-free analysis, which reveals the
      amplitude of spatial restriction for backbone N-NH bond vectors with respect to
      nano- to picosecond time-scale motions. Regions of well-defined secondary
      structure exhibited consistently low-amplitude spatial fluctuations, while the
      terminal and loop regions showed larger amplitude motions in the subnano- to
      picosecond time-scale. Interestingly, the C-terminal disulfide loop region that
      contains the receptor binding domain was found to be relatively rigid on the pico
      to nanosecond time-scale but exhibited motion in the micro- to millisecond time
      scale. It is notable that this disulfide loop displays a conserved antigenic
      epitope and mediates binding to the asialo-GM(1) cell surface receptor. The
      present study suggests that a rigid backbone scaffold mediates attachment to the
      host cell receptor, and also maintains the conformation of the conserved
      antigenic epitope for antibody recognition. In addition, slower millisecond time
      scale motions are likely to be crucial for conferring a range of specificity for
      these interactions. Characterization of pilin dynamics will aid in developing a
      detailed understanding of infection, and will facilitate the design of more
      efficient anti-adhesin synthetic vaccines and therapeutics against pathogenic
      bacteria containing type IV pili.

PMID- 11300780
TI  - Insight into the catalysis of hydrolysis of four newly synthesized substrates by
      papain: a proton inventory study.
AB  - We synthesized the following four new peptide substrates, Suc-Phe-Leu-pNA, Suc
      Phe-Leu-NMec, Suc-Phe-Leu-ONPh, and Pht-Phe-Leu-pNA, and we applied the proton
      inventory method to their hydrolysis by papain. Useful relationships between the
      rate constants of the catalytic reaction have been established and contributed to
      the elucidation of the hydrolytic mechanism of papain. For all amide substrates,
      the parameter K(S) and the rate constants k(1), k(-)(1), and k(2) were estimated.
      Moreover, it was found that k(cat)/K(m) = k(1) for all four substrates, while two
      exchangeable hydrogenic sites, one in the ground state and another in the
      transition state, generate an inverse isotope effect during the reaction governed
      by this parameter. The proton inventories of both k(2) and k(3) are essentially
      linear, whatever the acyl moiety and/or the leaving group of the substrate. The
      proton inventories of K(S) are also essentially linear for all amide substrates,
      while the observed large isotope effect of about 3 to 9 originates from a single
      hydrogenic site in the product state. This latter, in agreement to both the small
      transition state fractionation factors found for k(cat)/K(m) (or k(1)) and the
      unit ground-state fractionation factors found for k(2), argues for the formation
      of a tetrahedral adduct during the reaction governed by the k(1) parameter.
      Furthermore, papain acts as a one-proton catalyst during acylation or
      deacylation, both of which proceed through similar concerted reaction pathways,
      where a nucleophilic attack is accompanied by the movement of one proton.

PMID- 11300781
TI  - Profiling serine hydrolase activities in complex proteomes.
AB  - Serine hydrolases represent one of the largest and most diverse families of
      enzymes in higher eukaryotes, comprising numerous proteases, lipases, esterases,
      and amidases. The activities of many serine hydrolases are tightly regulated by
      posttranslational mechanisms, limiting the suitability of standard genomics and
      proteomics methods for the functional characterization of these enzymes. To
      facilitate the global analysis of serine hydrolase activities in complex
      proteomes, a biotinylated fluorophosphonate (FP-biotin) was recently synthesized
      and shown to serve as an activity-based probe for several members of this enzyme
      family. However, the extent to which FP-biotin reacts with the complete
      repertoire of active serine hydrolases present in a given proteome remains
      largely unexplored. Herein, we describe the synthesis and utility of a variant of
      FP-biotin in which the agent's hydrophobic alkyl chain linker was replaced by a
      more hydrophilic poly(ethylene glycol) moiety (FP-peg-biotin). When incubated
      with both soluble and membrane proteomes for extended reaction times, FP-biotin
      and FP-peg-biotin generated similar "maximal coverage" serine hydrolase activity
      profiles. However, kinetic analyses revealed that several serine hydrolases
      reacted at different rates with each FP agent. These rate differences were
      exploited in studies that used the biotinylated FPs to examine the target
      selectivity of reversible serine hydrolase inhibitors directly in complex
      proteomes. Finally, a general method for the avidin-based affinity isolation of
      FP-biotinylated proteins was developed, permitting the rapid and simultaneous
      identification of multiple serine peptidases, lipases, and esterases.
      Collectively, these studies demonstrate that chemical probes such as the
      biotinylated FPs can greatly accelerate both the functional characterization and
      molecular identification of active enzymes in complex proteomes.

PMID- 11300782
TI  - Spontaneous phosphorylation of the receptor with high affinity for IgE in
      transfected fibroblasts.
AB  - Receptors with high affinity for IgE, FcepsilonRI, which had been transfected
      into Chinese hamster ovary fibroblasts exhibit an over 20-fold greater
      spontaneous phosphorylation at physiological temperatures than the same receptors
      on the widely studied rat mucosal mast cell line, RBL-2H3. This enhanced
      phosphorylation was not accounted for either by changes in the src-family kinase
      responsible for the phosphorylation, by reduced activity of phosphatases, or by
      spontaneous association of the receptors with microdomains. A variety of
      approaches failed to detect evidence for stable spontaneous aggregates of the
      receptor. Whereas the altered posttranslational glycosylation of the receptor's
      principal ectodomain we detected could promote transient spontaneous aggregation
      and explain the observed effect, other changes in the membrane milieu cannot be
      excluded. The functional consequences of such spontaneous phosphorylation are
      considered.

PMID- 11300783
TI  - Relationship between excitation energy transfer, trapping, and antenna size in
      photosystem II.
AB  - We present a systematic study of the effect of antenna size on energy transfer
      and trapping in photosystem II. Time-resolved fluorescence experiments have been
      used to probe a range of particles isolated from both higher plants and the
      cyanobacterium Synechocystis 6803. The isolated reaction center dynamics are
      represented by a quasi-phenomenological model that fits the extensive time
      resolved data from photosystem II reaction centers and reaction center mutants.
      This representation of the photosystem II "trapping engine" is found to correctly
      predict the extent of, and time scale for, charge separation in a range of
      photosystem II particles of varying antenna size (8-250 chlorins). This work
      shows that the presence of the shallow trap and slow charge separation kinetics,
      observed in isolated D1/D2/cyt b559 reaction centers, are indeed retained in
      larger particles and that these properties are reflected in the trapping dynamics
      of all larger photosystem II preparations. A shallow equilibrium between the
      antennae and reaction center in photosystem II will certainly facilitate
      regulation via nonphotochemical quenching, and one possible interpretation of
      these findings is therefore that photosystem II is optimized for regulation
      rather than for efficiency.

PMID- 11300784
TI  - Vibrational structure of GDP and GTP bound to RAS: an isotope-edited FTIR study.
AB  - A complete vibrational description of the bonding of a ligand to a protein
      requires the assignment of both symmetric and antisymmetric vibrational modes.
      The symmetric modes of isotopically enriched enzyme-bound ligands can be obtained
      by Raman difference spectroscopy, but until now, the antisymmetric modes, which
      require IR difference spectroscopy, have not been generally accessible. We have
      developed the methodology needed to perform IR difference spectroscopy, assign
      the antisymmetric modes, and accurately describe bonding. The method is used to
      assess the bonding changes that occur as Mg.GDP and Mg.GTP move from solution
      into the active site of RAS. Binding to RAS opens the nonbridging, O--P--O angle
      of the gamma-phosphate of GTP by 2.7 degrees, yet the angular freedom (dispersion
      of the O--P--O angle) of the gamma-phosphate is comparable to that in solution.
      In contrast, the motion of the beta-phosphate of GDP is highly restricted,
      suggesting that it positions the gamma-phosphate for nucleophilic attack. The
      beta,gamma-bridging O-P bond of bound GTP is slightly weakened, being lengthened
      by 0.005 A in the active site, corresponding to a bond order decrease of 0.012
      valence unit (vu). The observed binding changes are consistent with a RAS
      mediated hydrolysis mechanism that parallels that for solution hydrolysis.

PMID- 11300785
TI  - Iron coordination in photosystem II: interaction between bicarbonate and the QB
      pocket studied by Fourier transform infrared spectroscopy.
AB  - The non heme iron environment of photosystem II is studied by light-induced
      infrared spectroscopy. A conclusion of previous work [Hienerwadel, R., and
      Berthomieu, C. (1995) Biochemistry 34, 16288-16297] is that bicarbonate is a
      bidendate ligand of the reduced iron and a monodentate ligand in the Fe(3+)
      state. In this work, the effects of bicarbonate replacement with lactate,
      glycolate, and glyoxylate, and of o-phenanthroline binding are investigated to
      determine the specific interactions of bicarbonate with the protein.
      Fe(2+)/Fe(3+) FTIR spectra recorded with (12)C- and (13)C(1)-labeled lactate
      indicate that lactate displaces bicarbonate by direct binding to the iron through
      one carboxylate oxygen and the hydroxyl group in both the Fe(2+) and Fe(3+)
      states. This different binding mode with respect to bicarbonate could explain the
      lower midpoint of the iron couple observed in the presence of this anion
      [Deligiannakis, Y., Petrouleas, V., and Diner, B. A. (1994) Biochim. Biophys.
      Acta 1188, 260-270]. In agreement with the -60 mV/pH unit dependence of the iron
      midpoint potential in the presence of bicarbonate, the proton release upon iron
      oxidation by photosystem II is directly measured to 0.95 +/- 0.05 by the
      comparison of infrared signals of phosphate buffer and ferrocyanide modes. This
      accurate method may be applied to the study of other redox reactions in proteins.
      The pH dependence of the iron couple is proposed to reflect the deprotonation of
      D1His215, a putative iron ligand located at the Q(B) pocket, since the signal at
      1094 cm(-1) assigned to the nu(C-N) mode of a histidinate ligand in the Fe(3+)
      state is not observed in the presence of o-phenanthroline. Specific regulation of
      the pK(a) of D1His215 by bicarbonate is inferred from the absence of the band at
      1094 cm(-1) in Fe(2+)/Fe(3+) spectra recorded with glycolate, glyoxylate, or
      lactate. A broad positive continuum, maximum at approximately 2550 cm(-1),
      observed in the presence of bicarbonate, but absent with o-phenanthroline or
      lactate, glycolate, and glyoxylate, indicates a hydrogen bond network from the
      non heme iron toward the Q(B) pocket involving bicarbonate and His D1-215. Proton
      release of about 1, measured upon iron oxidation at pH 6 with the latter anions,
      points to a proton release mechanism different from that involved in the presence
      of bicarbonate.

PMID- 11300786
TI  - Site-specific phosphorylation of human p53 protein determined by mass
      spectrometry.
AB  - Human recombinant p53 (r-p53) protein was studied by mass spectrometry (MS) to
      determine site-specific posttranslational differences between basal and
      hyperphosphorylated r-p53. Wild-type p53 was basally expressed after baculovirus
      infection while a parallel preparation was treated with the phosphatase inhibitor
      okadaic acid during the terminal stages of expression to create a
      hyperphosphorylated form of p53 known for its higher DNA binding and
      transcriptional activation. After immunoaffinity and HPLC purification, MALDI/MS
      measured a higher molecular mass for r-p53 from okadaic acid treatment relative
      to control, suggesting a higher phosphorylation state. This was supported by an
      acidic shift of r-p53 isoforms separated by gel isoelectric focusing. Employing a
      variety of mass spectrometric analyses combined with separation and affinity
      techniques, six specific phosphorylation sites of p53 were identified. The MS
      data indicated that hyperphosphorylated p53 showed a higher degree of
      phosphorylation than basal p53 at specific amino- and carboxy-terminal sites. In
      particular, ESI-MS demonstrated that Ser(315) was entirely phosphorylated after
      okadaic acid treatment, as confirmed biochemically by CDK2 kinase assay and by
      isoelectric focusing. In summary, MS analysis uniquely revealed increased, site
      specific phosphorylations on p53 after phosphatase inhibition, particularly at
      Ser(315), which may be critical molecular events in defining p53 activity.

PMID- 11300787
TI  - Ascorbate inhibits the carbethoxylation of two histidyl and one tyrosyl residues
      indispensable for the transmembrane electron transfer reaction of cytochrome
      b561.
AB  - Cytochrome b(561) from bovine adrenal chromaffin vesicles contains two heme B
      prosthetic groups and transports electron equivalents across the vesicle
      membranes to convert intravesicular monodehydroascorbate radical to ascorbate. We
      found previously that treatment of oxidized cytochrome b(561) with diethyl
      pyrocarbonate caused specific N-carbethoxylation of three fully conserved
      residues (His88, His161, and Lys85) located at the extravesicular side. The
      modification lead to a selective loss of the electron-accepting ability from
      ascorbate without affecting the electron donation to monodehydroascorbate radical
      [Tsubaki, M., Kobayashi, K., Ichise, T., Takeuchi, F., and Tagawa, S. (2000)
      Biochemistry 39, 3276-3284]. In the present study, we found that these
      modifications lead to a drastic decrease of the midpoint potential of heme b at
      the extravesicular side from +60 to -30 mV. We found further that the O
      carbethoxylation of one tyrosyl residue (Tyr218) located at the extravesicular
      side was significantly enhanced under alkaline conditions, leading to a very slow
      reduction process of the oxidized heme b with ascorbate. On the other hand, the
      presence of ascorbate during the treatment with diethyl pyrocarbonate was found
      to suppress the carbethoxylation of His88, His161, and Tyr218, whereas the
      modification level of Lys85 was not affected. Concomitantly, the final reduction
      level of heme b with ascorbate was protected, although the fast reduction phase
      was not fully restored. These results suggest that the two heme-coordinating
      histidyl residues (His88 and His161) are also a part of the ascorbate binding
      site. Tyr218 and Lys85 may have a role in the recognition/binding process for
      ascorbate and are indispensable for the fast electron transfer reaction.

PMID- 11300788
TI  - Functional proteomics: examining the effects of hypoxia on the cytotrophoblast
      protein repertoire.
AB  - The outcome of human pregnancy depends on the differentiation of
      cytotrophoblasts, specialized placental cells that physically connect the
      embryo/fetus to the mother. As cytotrophoblasts differentiate, they acquire tumor
      like characteristics that enable them to invade the uterus. In a novel feedback
      loop, the increasingly higher levels of oxygen they encounter within the uterine
      wall influence their differentiation into vascular-like cells. Together, the
      invasive and cell surface properties of cytotrophoblasts enable them to form
      vascular connections with uterine blood vessels that divert maternal blood flow
      to the placenta, a critical hurdle in pregnancy. It is therefore important to
      understand how cytotrophoblasts respond to changes in oxygen tension. Here we
      used a proteomics approach, two-dimensional polyacrylamide gel electrophoresis (2
      D PAGE) combined with mass spectrometry, to characterize the protein repertoire
      of first trimester human cytotrophoblasts that were maintained under standard
      tissue culture conditions (20% O(2)). 2-D PAGE showed a unique protein map as
      compared to placental fibroblasts and human JEG-3 choriocarcinoma cells. Mass
      spectrometry allowed the identification of 43 spots on the cytotrophoblast map.
      Enzymes involved in glycolysis and responses to oxidative stress, as well as the
      14-3-3 signaling/adapter proteins, were particularly abundant. Hypoxia in vitro
      (2% O(2)) produced discrete changes in the expression of a subset of proteins in
      all the aforementioned functional categories. Together, these data offer new
      information about the early gestation cytotrophoblast protein repertoire and the
      generalized mechanisms the cells use to respond to changes in oxygen tension at
      the maternal-fetal interface.

PMID- 11300789
TI  - The Y181C mutant of HIV-1 reverse transcriptase resistant to nonnucleoside
      reverse transcriptase inhibitors alters the size distribution of RNase H
      cleavages.
AB  - We investigated the effects of the nonnucleoside reverse transcriptase inhibitor
      resistant mutant Y181C on RNA 5'-end-directed RNase H cleavage by HIV-1 reverse
      transcriptase, using an RNA.DNA hybrid in which a radiolabeled RNA 5' end was
      recessed. Y181C produced a higher ratio of secondary (9 nucleotide long) to
      primary (18 nucleotide long) products than wild type. When the RNA was 3'-end
      labeled, Y181C generated a long product, which results when secondary cleavage
      precedes the primary. When using an RNA.DNA hybrid in which the labeled RNA 5'
      end and DNA 3' end were flush, formation of secondary product by both enzymes was
      inhibited. Under these conditions, Y181C cleaved closer to the RNA 5' end than
      wild type. Studies with this substrate labeled at the RNA 3' end showed that
      Y181C is no more likely than wild type to cleave toward the RNA 3' end. Thus,
      Y181C RT has a strong preference to cleave in the direction of the RNA 5' end
      even when secondary cleavage is prevented, resulting in a disruption of the
      normal sequence of primary followed by secondary cleavages.

PMID- 11300790
TI  - Mapping psoralen cross-links at the nucleotide level in mammalian cells:
      suppression of cross-linking at transcription factor- or nucleosome-binding
      sites.
AB  - We have developed a new genomic sequencing method for detecting, with resolution
      at the nucleotide level, the interstrand DNA cross-links induced by 4,5',8
      trimethylpsoralen along single-copy genes in mammalian cells. The cross-links
      (diadducts) initially formed are converted into monoadducts by alkali reversal
      prior to the use of terminal transferase-dependent PCR (TD-PCR). After alkali
      reversal, but not before, the DNA strands can be separated and used as templates
      for gene-specific primer extension, which is the first step in the TD-PCR
      procedure. The converted psoralen adducts block primer extension, and the
      prematurely terminated single-stranded products are then amplified by TD-PCR and
      visualized on a sequencing gel. Adducts formed by angelicin, a psoralen
      derivative that forms only monoadducts, were also investigated by use of TD-PCR.
      Comparison of the adduct distribution patterns of in vivo-treated DNA with those
      of in vitro-treated DNA revealed that the binding of transcription factors
      inhibited both psoralen cross-linking and angelicin monoadduct formation in the c
      JUN and c-FOS promoters in living human cells. Adduct formation was also
      inhibited in the region of a putative positioned nucleosome in the c-FOS
      promoter. These methods should be of general use for study of in vivo protein-DNA
      interactions and DNA repair.

PMID- 11300791
TI  - Miscoding potential of the N2-ethyl-2'-deoxyguanosine DNA adduct by the
      exonuclease-free Klenow fragment of Escherichia coli DNA polymerase I.
AB  - Acetaldehyde, a major metabolite of ethanol, reacts with dG residues in DNA,
      resulting in the formation of the N(2)-ethyl-2'-deoxyguanosine (N(2)-Et-dG)
      adduct. This adduct has been detected in lymphocyte DNA of alcohol abusers. To
      explore the miscoding property of the N(2)-Et-dG DNA adduct, phosphoramidite
      chemical synthesis was used to prepare site-specifically modified
      oligodeoxynucleotides containing a single N(2)-Et-dG. These N(2)-Et-dG-modified
      oligodeoxynucleotides were used as templates for primer extension reactions
      catalyzed by the 3' --> 5' exonuclease-free (exo(-)) Klenow fragment of
      Escherichia coli DNA polymerase I. The primer extension was retarded one base
      prior to the N(2)-Et-dG lesion and opposite the lesion; however, when the enzyme
      was incubated for a longer time or with increased amounts of this enzyme, full
      extension occurred. Quantitative analysis of the fully extended products showed
      the preferential incorporation of dGMP and dCMP opposite the N(2)-Et-dG lesion,
      accompanied by a small amounts of dAMP and dTMP incorporation and one- and two
      base deletions. Steady-state kinetic studies were also performed to determine the
      frequency of nucleotide insertion opposite the N(2)-Et-dG lesion and chain
      extension from the 3' terminus from the dN.N(2)-Et-dG (N is C, A, G, or T) pairs.
      These results indicate that the N(2)-Et-dG DNA adduct may generate G --> C
      transversions in living cells. Such a mutational spectrum has not been detected
      with other methylated dG adducts, including 8-methyl-2'-deoxyguanosine, O(6)
      methyl-2'-deoxyguanosine, and N(2)-methyl-2'-deoxyguanosine. In addition, N(2)
      ethyl-2'-deoxyguanosine triphosphate (N(2)-Et-dGTP) was efficiently incorporated
      opposite a template dC during DNA synthesis catalyzed by the exo(-) Klenow
      fragment. The utilization of N(2)-Et-dGTP was also determined by steady-state
      kinetic studies. N(2)-Et-dG DNA adducts are also formed by the incorporation of
      N(2)-Et-dGTP into DNA and may cause mutations, leading to the development of
      alcohol- and acetaldehyde-induced human cancers.

PMID- 11300792
TI  - Resonance Raman studies of cytochrome c' support the binding of NO and CO to
      opposite sides of the heme: implications for ligand discrimination in heme-based
      sensors.
AB  - Resonance Raman (RR) studies have been conducted on Alcaligenes xylosoxidans
      cytochrome c', a mono-His ligated hemoprotein which reversibly binds NO and CO
      but not O(2). Recent crystallographic characterization of this protein has
      revealed the first example of a hemoprotein which can utilize both sides of its
      heme (distal and proximal) for binding exogenous ligands to its Fe center. The
      present RR investigation of the Fe coordination and heme pocket environments of
      ferrous, carbonyl, and nitrosyl forms of cytochrome c' in solution fully supports
      the structures determined by X-ray crystallography and offers insights into
      mechanisms of ligand discrimination in heme-based sensors. Ferrous cytochrome c'
      reacts with CO to form a six-coordinate heme-CO complex, whereas reaction with NO
      results in cleavage of the proximal linkage to give a five-coordinate heme-NO
      adduct, despite the relatively high stretching frequency (231 cm(-1)) of the
      ferrous Fe-N(His) bond. RR spectra of the six-coordinate CO adduct indicate that
      CO binds to the Fe in a nonpolar environment in line with its location in the
      hydrophobic distal heme pocket. On the other hand, RR data for the five
      coordinate NO adduct suggest a positively polarized environment for the NO
      ligand, consistent with its binding close to Arg 124 on the opposite (proximal)
      side of the heme. Parallels between certain physicochemical properties of
      cytochrome c' and those of heme-based sensor proteins raise the possibility that
      the latter may also utilize both sides of their hemes to discriminate between NO
      and CO binding.

PMID- 11300793
TI  - Inactivation of pyruvate formate-lyase by dioxygen: defining the mechanistic
      interplay of glycine 734 and cysteine 419 by rapid freeze-quench EPR.
AB  - Pyruvate formate-lyase from Escherichia coli (EC 2.3.1.54; PFL) catalyzes the
      reversible anaerobic conversion of pyruvate and CoA into acetyl-CoA and formate.
      Active PFL contains a novel alpha-carbon centered glycyl radical at G734 that is
      required for its catalytic activity. Two adjacent cysteine residues, C418 and
      C419, are essential for PFL activity according to site-directed mutagenesis
      studies. Upon exposure to air, active PFL loses its activity with the concomitant
      loss of the glycyl radical. Previous EPR studies of dioxygen inactivation of PFL
      revealed protein-based peroxyl and sulfinyl radicals during the manual mixing and
      quenching process [Reddy et al. (1998) Biochemistry 37, 558-563]. To probe the
      mechanism of this process, we carried out experiments using rapid freeze-quench
      EPR spectroscopy. Upon mixing of active wild type or C418A PFL with oxygenated
      solution, a short-lived radical intermediate appears at the earliest time point
      (10 ms), followed by the appearance of a long-lived sulfinyl radical. The axial
      EPR spectrum of this short-lived radical (g = 2.034, 2.007) is characteristic of
      a peroxyl radical. When C419A PFL or the double mutant [C418A/C419A] PFL was
      mixed with oxygenated solution, the peroxyl radical was also observed at 10 ms
      but in this case persisted over 12 s. These observations provide compelling
      evidence to support a proposed mechanism in which dioxygen quenches the glycyl
      radical in the active enzyme and the resulting peroxyl radical may react further
      with the sulfhydryl group of the C419 residue to form the sulfinyl radical.

PMID- 11300794
TI  - Functional analysis of combinatorial mutants with changes in the C-terminus of
      the CD loop of the D2 protein in photosystem II of Synechocystis sp. PCC 6803.
AB  - Photosystem II properties were investigated in a set of combinatorial mutants
      containing changes in the C-terminal end of the CD lumenal loop (Gly187-Asn194)
      in the D2 protein of Synechocystis sp. PCC 6803. Initial screening of variable
      fluorescence (F(v)) induction and decay in the presence of DCMU showed that all
      but one of the combinatorial strains tested had an increased rate of Q(A)(-)
      reoxidation. Two strains showed an increase in the amplitude of constant
      fluorescence (F(o)). Examination of the primary sequence of the combinatorial
      strains combined with results obtained from analysis of site-directed mutants
      suggested that alterations in residue 191 of D2 increased the rate of charge
      recombination. Indeed, reintroduction of Trp191, the residue present in wild
      type, slowed the Q(A)(-) reoxidation rate in the presence of DCMU by 2-3-fold.
      However, the nature of other residues, in particular at codon 192, was also
      important in determining charge recombination rates. The increase in F(o) yield
      was due to an increased fluorescence lifetime of open reaction centers in intact
      cells and may reflect a decreased excitation trapping rate in the reaction
      center. This change was reversed by reintroduction of Trp191 even though a mutant
      lacking just Trp191 was normal in this respect. Trapping efficiency therefore was
      decreased only when multiple changes were present at the same time. We interpret
      Trp191 and neighboring residues to influence the midpoint redox potential of
      P680/P680(+) and in certain sequence contexts to affect the energy trapping
      efficiency by P680. The stability or environment of Y(D)(ox) was essentially
      unaffected in the mutants. Interestingly, many combinatorial mutants displayed an
      increased requirement for chloride for photoautotrophic growth, and two mutants,
      C8-10 and C8-23, also required more calcium. This indicates that this CD loop
      region of D2 not only affects properties of P680 but also affects properties of
      the oxygen-evolving complex.

PMID- 11300795
TI  - Persistent binding of MgADP to the E187A mutant of Escherichia coli
      phosphofructokinase in the absence of allosteric effects.
AB  - MgADP binding to the allosteric site enhances the affinity of Escherichia coli
      phosphofructokinase (PFK) for fructose 6-phosphate (Fru-6-P). X-ray
      crystallographic data indicate that MgADP interacts with the conserved glutamate
      at position 187 within the allosteric site through an octahedrally coordinated
      Mg(2+) ion [Shirakihara, Y., and Evans, P. R. (1988) J. Mol. Biol. 204, 973-994].
      Lau and Fersht reported that substituting an alanine for this glutamate within
      the allosteric site of PFK (i.e., mutant E187A) causes MgADP to lose its
      allosteric effect upon Fru-6-P binding [Lau, F. T.-K., and Fersht, A. R. (1987)
      Nature 326, 811-812]. However, these authors later reported that MgADP inhibits
      Fru-6-P binding in the E187A mutant. The inhibition presumably occurs by
      preferential binding to the inactive (T) state complex of the Monod-Wyman
      Changeux two-state model [Lau, F. T.-K., and Fersht, A. R. (1989) Biochemistry
      28, 6841-6847]. The present study provides an alternative explanation of the role
      of MgADP in the E187A mutant. Using enzyme kinetics, steady-state fluorescence
      emission, and anisotropy, we performed a systematic linkage analysis of the three
      ligand interaction between MgADP, Fru-6-P, and MgATP. We found that MgADP at low
      concentrations did not enhance or inhibit substrate binding. Anisotropy shows
      that MgADP binding at the allosteric site occurred even when MgADP produced no
      allosteric effect. However, as in the wild-type enzyme, the binding of MgADP to
      the active site in the mutant competitively inhibited MgATP binding and
      noncompetitively inhibited Fru-6-P binding. These results clarified the mechanism
      of a three-ligand interaction and offered a nontraditional perspective on
      allosteric mechanism.

PMID- 11300796
TI  - MgATP-dependent activation by phosphoenolpyruvate of the E187A mutant of
      Escherichia coli phosphofructokinase.
AB  - Using enzymatic assays and steady-state fluorescence emission, we performed a
      linkage analysis of the three-ligand interaction of fructose 6-phosphate (Fru-6
      P), phosphoenolpyruvate (PEP), and MgATP on E187A mutant Escherichia coli
      phosphofructokinase (PFK). PEP allosterically inhibits Fru-6-P binding to E. coli
      PFK. The magnitude of antagonism is 90-fold in the absence and 60-fold in the
      presence of a saturating concentration of MgATP [Johnson, J. J., and Reinhart, G.
      D. (1997) Biochemistry 36, 12814-12822]. Substituting an alanine for the
      glutamate at position 187, located in the allosteric site (i.e., mutant E187A),
      activates Fru-6-P binding and inhibits the maximal rate of enzyme turnover [Lau,
      F. T.-K., and Fersht, A. R. (1987) Nature 326, 811-812]. The allosteric action of
      PEP appears to depend on the presence of the cosubstrate MgATP. In the presence
      of a saturating concentration of MgATP, PEP enhances the binding of Fru-6-P to
      the enzyme by a modest 2-fold. Decreasing the concentration of MgATP mitigates
      the extent of activation. At MgATP concentrations approaching 25 microM, PEP
      becomes insensitive to the binding of Fru-6-P. At MgATP concentrations < 25
      microM, PEP "crosses over" and becomes antagonistic toward substrate binding. The
      present study examines the role of Glu 187 at the allosteric site in the binding
      of Fru-6-P and offers a more complex explanation of the mechanism than that
      described by traditional allosteric mechanistic models.

PMID- 11300797
TI  - Functional reassembly of ATP-dependent xenobiotic transport by the N- and C
      terminal domains of RLIP76 and identification of ATP binding sequences.
AB  - We have recently shown that RLIP76, a Ral-binding, GTPase-activating protein, is
      an ATP-dependent transporter of doxorubicin (DOX) as well as glutathione
      conjugates [Awasthi, S., et al. (2000) Biochemistry 39, 9327-9334]. RLIP76
      overexpressed in human cells or transformed E. coli undergoes proteolysis to
      yield several fragments, including two prominent peptides, N-RLIP76(1-367) and C
      RLIP76(410-655), from the N- and C-terminal domains, respectively. To investigate
      whether the fragmentation of RLIP76 has any relevance to its transport function,
      we have studied the characteristics of these two peptide fragments. Recombinant N
      RLIP76(1-367) and C-RLIP76(410-655) were purified from overexpressing transformed
      E. coli. While N-RLIP76(1-367) readily underwent proteolysis, showing SDS-gel
      patterns similar to those of RLIP76, C-RLIP76(410-655) was resistant to such
      degradation. Both N-RLIP76(1-367) and C-RLIP76(410-655) had ATPase activity (K(m)
      for ATP, 2.5 and 2.0 mM, respectively) which was stimulated by DNP-SG, DOX, and
      colchicine (COL). ATP binding to both peptides was confirmed by photoaffinity
      labeling with 8-azido-ATP that was increased in the presence of compounds that
      stimulated their ATPase activity. Photoaffinity labeling was also increased in
      the presence of vanadate, indicating trapping of a reaction intermediate in the
      ATP binding site. The ATP binding sites in N-RLIP76(1-367) and C-RLIP76(410-655)
      were identified to be (69)GKKKGK(74) and (418)GGIKDLSK(425), respectively.
      Mutation of K(74) and K(425) to M residues, in N-RLIP76(1-367) and C-RLIP76(410
      655), respectively, abrogated their ATPase activity as well as azido-ATP
      labeling. Proteoliposomes reconstituted with either N-RLIP76(1-367) or C
      RLIP76(410-655) alone did not catalyze ATP-dependent transport of DOX or COL.
      However, proteoliposomes reconstituted with a mixture of N-RLIP76(1-367) and C
      RLIP76(410-655) mediated such transport. Proteoliposomes reconstituted with the
      mixture of mutant peptides lacking ATPase activity did not exhibit transport
      activity. Present studies have identified the ATP binding sites in RLIP76, and
      show that DOX and COL transport can be reconstituted by two fragments of RLIP76.

PMID- 11300798
TI  - Membrane interactions of a novel viral enterotoxin: rotavirus nonstructural
      glycoprotein NSP4.
AB  - The rotavirus enterotoxin, NSP4, is a novel secretory agonist that also plays a
      role in the unique rotavirus morphogenesis that involves a transient budding of
      newly made immature viral particles into the endoplasmic reticulum. NSP4 and an
      active peptide corresponding to NSP4 residues 114 to 135 (NSP4(114-135)) mobilize
      intracellular calcium and induce secretory chloride currents when added
      exogenously to intestinal cells or mucosa. Membrane-NSP4 interactions may
      contribute to these alterations; however, details of a lipid-binding domain are
      unresolved. Therefore, circular dichroism was used to determine (i) the
      interaction(s) of NSP4 and NSP4(114-135) with model membranes, (ii) the
      conformational changes elicited in NSP4 upon interacting with membranes, (iii) if
      NSP4(114-135) is a membrane interacting domain, and (iv) the molar dissociation
      constant (K(d)) of NSP4(114-135) with defined lipid vesicles. Circular dichroism
      revealed for the first time that NSP4 and NSP4(114-135) undergo secondary
      structural changes upon interaction with membrane vesicles. This interaction was
      highly dependent on both the membrane surface curvature and the lipid
      composition. NSP4 and NSP4(114-135) preferentially interacted with highly curved,
      small unilamellar vesicle membranes (SUV), but significantly less with low
      curvature, large unilamellar vesicle membranes (LUV). Binding to SUV, but not
      LUV, was greatly enhanced by negatively charged phospholipids. Increasing the SUV
      cholesterol content, concomitant with the presence of negatively charged
      phospholipids, further potentiated the interaction of NSP4(114-135) with the SUV
      membrane. The K(d) of NSP4(114-135) was determined as well as partitioning of
      NSP4(114-135) with SUVs in a filtration-binding assay. These data confirmed NSP4
      and its active peptide interact with model membranes that mimic caveolae.

PMID- 11300799
TI  - Domain formation in a fluid mixed lipid bilayer modulated through binding of the
      C2 protein motif.
AB  - The role and mechanism of formation of lipid domains in a functional membrane
      have generally received limited attention. Our approach, based on the hypothesis
      that thermodynamic coupling between lipid-lipid and protein-lipid interactions
      can lead to domain formation, uses a combination of an experimental lipid bilayer
      model system and Monte Carlo computer simulations of a simple model of that
      system. The experimental system is a fluid bilayer composed of a binary mixture
      of phosphatidylcholine (PC) and phosphatidylserine (PS), containing 4% of a
      pyrene-labeled anionic phospholipid. Addition of the C2 protein motif (a
      structural domain found in proteins implicated in eukaryotic signal transduction
      and cellular trafficking processes) to the bilayer first increases and then
      decreases the excimer/monomer ratio of the pyrene fluorescence. We interpret this
      to mean that protein binding induces anionic lipid domain formation until the
      anionic lipid becomes saturated with protein. Monte Carlo simulations were
      performed on a lattice representing the lipid bilayer to which proteins were
      added. The important parameters are an unlike lipid-lipid interaction term and an
      experimentally derived preferential protein-lipid interaction term. The
      simulations support the experimental conclusion and indicate the existence of a
      maximum in PS domain size as a function of protein concentration. Thus, lipid
      protein coupling is a possible mechanism for both lipid and protein clustering on
      a fluid bilayer. Such domains could be precursors of larger lipid-protein
      clusters ('rafts'), which could be important in various biological processes such
      as signal transduction at the level of the cell membrane.

PMID- 11300800
TI  - Phosphorylation mutants elucidate the mechanism of annexin IV-mediated membrane
      aggregation.
AB  - Site-directed mutagenesis, electron microscopy, and X-ray crystallography were
      used to probe the structural basis of annexin IV-induced membrane aggregation and
      the inhibition of this property by protein kinase C phosphorylation. Site
      directed mutants that either mimic (Thr6Asp, T6D) or prevent (Thr6Ala, T6A)
      phosphorylation of threonine 6 were produced for these studies and compared with
      wild-type annexin IV. In vitro assays showed that unmodified wild-type annexin IV
      and the T6A mutant, but not PKC-phosphorylated wild-type or the T6D mutant,
      promote vesicle aggregation. Electron crystallographic data of wild-type and T6D
      annexin IV revealed that, similar to annexin V, the annexin IV proteins form 2D
      trimer-based ordered arrays on phospholipid monolayers. Cryo-electron microscopic
      images of junctions formed between lipid vesicles in the presence of wild-type
      annexin IV indicated a separation distance corresponding to the thickness of two
      layers of membrane-bound annexin IV. In this orientation, a single layer of WT
      annexin IV, attached to the outer leaflet of one vesicle, would undergo face-to
      face self-association with the annexin layer of a second vesicle. The 2.0-A
      resolution crystal structure of the T6D mutant showed that the mutation causes
      release of the N-terminal tail from the protein core. This change would preclude
      the face-to-face annexin self-association required to aggregate vesicles. The
      data suggest that reversible complex formation through phosphorylation and
      dephosphorylation could occur in vivo and play a role in the regulation of
      vesicle trafficking following changes in physiological states.

PMID- 11300802
TI  - Organic soluble silicophosphonate [RSi(OH)(OP(O)(H)(OH))](2)O (R=(2,6-i
      Pr(2)C(6)H(3)NSiMe(3)): the first silicophosphonate containing free Si--OH and P-
      OH groups..

PMID- 11300803
TI  - Diverse solid-state and solution structures within a series of hexaamine
      dicopper(II) complexes.
AB  - Mono- and dicopper(II) complexes of a series of potentially bridging hexaamine
      ligands have been prepared and characterized in the solid state by X-ray
      crystallography. The crystal structures of the following Cu(II) complexes are
      reported: [Cu(HL3)](ClO4)(3), C11H31Cl3CuN6O12, monoclinic, P2(1)/n, a = 8.294(2)
      A, b = 18.364(3) A, c = 15.674(3) A, beta = 94.73(2) degrees, Z = 4;
      ([Cu2(L4)(CO3)](2))(ClO4)(4).4H2O, C40H100Cl4Cu4N12O26, triclinic, P1, a =
      9.4888(8) A, b = 13.353(1) A, c = 15.329(1) A, alpha = 111.250(7) degrees, beta =
      90.068(8) degrees, gamma = 105.081(8) degrees, Z = 1; [Cu2(L5)(OH2)(2)](ClO4)(4),
      C13H36Cl4Cu2N6O18, monoclinic, P2(1)/c, a = 7.225(2) A, b = 8.5555(5) A, c =
      23.134(8) A, beta = 92.37(1) degrees, Z = 2; [Cu2(L6)(OH2)(2)](ClO4)(4).3H2O,
      C14H44Cl4Cu2N6O21, monoclinic, P2(1)/a, a = 15.204(5) A, b = 7.6810(7) A, c =
      29.370(1) A, beta = 100.42(2) degrees, Z = 4. Solution spectroscopic properties
      of the bimetallic complexes indicate that significant conformational changes
      occur upon dissolution, and this has been probed with EPR spectroscopy and
      molecular mechanics calculations.

PMID- 11300804
TI  - Novel dinuclear luminescent compounds based on iridium(III) cyclometalated
      chromophores and containing bridging ligands with ester-linked chelating sites.
AB  - The syntheses and study of the spectroscopic, redox, and photophysical properties
      of a new set of species based on Ir(III) cyclometalated building blocks are
      reported. This set includes three dinuclear complexes, that is, the symmetric
      (with respect to the bridging ligand) diiridium species [(ppy)(2)Ir(mu-L-OC(O)
      C(O)O-L)Ir(ppy)(2)][PF(6)](2) (5; ppy = 2-phenylpyridine anion; L-OC(O)-C(O)O-L =
      bis[4-(6'-phenyl-2,2'-bipyridine-4'-yl)phenyl]-benzene-1,4-dicarboxylate), the
      asymmetric diiridium species [(ppy)(2)Ir(mu-L-OC(O)-L)Ir(ppy)(2)][PF(6)](2) (3; L
      OC(O)-L = 4-([(6'-phenyl-2,2'-bipyridine-4'-yl)benzoyloxy]phenyl)-6'-phenyl-2,2'
      bipyridine), and the mixed-metal Ir-Re species [(ppy)(2)Ir(mu-L-OC(O)
      L)Re(CO)(3)Br][PF(6)] (4). Syntheses, characterization, and spectroscopic,
      photophysical, and redox properties of the model mononuclear compounds
      [Ir(ppy)(2)(L-OC(O)-L)][PF(6)] (2) and [Re(CO)(3)(L-COOH)Br] (6; L-COOH = 4'-(4
      carboxyphenyl)-6'-phenyl-2,2'-bipyridine) are also reported, together with the
      syntheses of the new bridging ligands L-OC(O)-L and L-OC(O)-C(O)O-L. The
      absorption spectra of all the complexes are dominated by intense spin-allowed
      ligand-centered (LC) bands and by moderately intense spin-allowed metal-to-ligand
      charge-transfer (MLCT) bands. Spin-forbidden MLCT absorption bands are also
      visible as low-energy tails at around 470 nm for all the complexes. All the new
      species exhibit metal-based irreversible oxidation and bipyridine-based
      reversible reduction processes in the potential window investigated (between
      +1.80 and -1.70 V vs SCE). The redox behavior indicates that the metal-based
      orbitals are only weakly interacting in dinuclear systems, whereas the two
      chelating halves of the bridging ligands exhibit noticeable electronic
      interactions. All the complexes are luminescent both at 77 K and at room
      temperature, with emission originating from triplet MLCT states. The luminescence
      properties are temperature- and solvent-dependent, in accord with general
      theories: emission lifetimes and quantum yields increase on passing from
      acetonitrile to dichloromethane fluid solution and from room-temperature fluid
      solution to 77 K rigid matrix. In the dinuclear mixed-chromophore species 3 and
      4, photoinduced energy transfer across the ester-linked bridging ligands seems to
      occur with low efficiency.

PMID- 11300805
TI  - Reaction of 2,4,6-triazido-1,3,5-triazine with triphenylphosphane. syntheses and
      characterization of the novel 2-triphenylphosphanimino-4-azidotetrazolo[5,1-a]
      [1,3,5]triazine and 2,4,6,-tris(triphenylphosphanimino)-1,3,5-triazine.
AB  - 2-Triphenylphosphanimino-4-azidotetrazolo[5,1-a]-[1,3,5]triazine (6) was obtained
      by reaction of 2,4,6-triazido-1,3,5-triazine (1) with 1 equiv of
      triphenylphosphane. Raman and X-ray data revealed that only one azide group
      formed a tetrazole ring system whereas the second azide group did not undergo
      ring closure. To investigate the equilibrium between the tetrazole isomer and the
      open-chain azide structure for these and related species, (31)P NMR studies were
      carried out. The obtained spectra displayed an equilibrium between the tetrazole
      and the open-chain azide isomers. 2,4,6-Tris(triphenylphosphanimino)-1,3,5
      triazine (4) was prepared by treatment of 1 with 3 equiv of triphenylphosphane,
      and its X-ray structure is discussed. On the basis of PM3 semiempirical and
      density functional calculations, the reaction of 1 with triphenylphosphane was
      studied. The thermodynamics of different isomerization reactions and the
      activation barriers to cyclization were estimated.

PMID- 11300806
TI  - Optical, magnetic, and electronic properties of peripherally fused macrocycles:
      molybdocene porphyrazines.
AB  - Metal-free and copper porphyrazines, [H(2)pz] and [Cu pz], have been fused at the
      periphery with molybdocene dithiolene, [Cp(2)Mo]. The optical, magnetic, and
      electronic properties of the resulting neutral and cationic complexes are
      studied, using first-principles density functional theory implemented by the
      discrete variational method. Analysis of the charge and spin distribution shows
      that the porphyrazine core is strongly coupled with the peripheral complex. The
      calculated optical absorption is found to be in reasonable agreement with
      experimental spectra, lending support to our theoretical model. Under appropriate
      circumstances one observes interaction of unpaired spins localized in the
      vicinity of both metal sites. The calculated spin distribution shows that
      [Cp(2)Mo][Cu pz] and [Cp(2)Mo][H(2)pz](+) have a magnetic moment of 1 micro(B)
      while [Cp(2)Mo][Cu pz](+) and [Cp(2)Mo][H(2)pz] have no moment, in good agreement
      with the results of X-band EPR spectra. The Cu-Mo magnetic interaction is
      antiferromagnetic, being mediated by pyrrol nitrogens, meso nitrogens, carbons,
      and sulfurs.

PMID- 11300807
TI  - Solid-state structure and solution behavior of eight-coordinate Sm(III)
      poly(pyrazolyl)borate compounds.
AB  - [Sm(Tp(Me2)(2)(kappa(2)-S(2)CNR(2))] compounds (R = Et (1), Me (2); Tp(Me2) =
      HB(3,5-Me2pz)(3)) have been isolated from reaction of (R(2)NC(S)S)(2) with 2
      equiv of [Sm(Tp(Me2)(2)]. Reductive cleavage of 2,2'-dipyridyl disulfide or 2,2'
      dipyridyl diselenide by [Sm(Tp(Me2)(2)] afforded good yields of
      [Sm(Tp(Me2)(2)(kappa(2)-Y)] compounds (Y = 2-SC(5)H(4)N (3), 2-SeC(5)H(4)N (4)).
      4 is the first selenopyridine complex of an f-block element. Sm(Tp(Me2)(2)(2
      OC(5)H(4)N) (5) has been synthesized by salt metathesis of [Sm(Tp(Me2)(2)Cl] with
      the sodium salt of the 2-hydroxypyridine. The solid-state structures of 1, 3, 4,
      and 5 were determined by single-crystal X-ray diffraction analysis and revealed
      that the compounds are all eight-coordinate with dodecahedral geometry. The
      samarium atoms are bound in tridentate fashion to two pyrazolylborate ligands and
      in bidentate fashion by the third ligand. The solution behavior of the compounds
      was studied by (1)H NMR techniques. (1)H-(1)H exchange spectroscopy experiments
      give evidence for two distinct dynamic regimes occurring in solution.

PMID- 11300808
TI  - Chemical control on the coordination mode of benzaldehyde semicarbazone ligands.
      synthesis, structure, and redox properties of ruthenium complexes.
AB  - Reaction of benzaldehyde semicarbazone (HL-R, where H is a dissociable proton and
      R is a substituent (R = OMe, Me, H, Cl, NO(2)) at the para position of the phenyl
      ring) with [Ru(PPh(3))(3)Cl(2)] and [Ru(PPh(3))(2)(CO2)Cl2] has afforded
      complexes of different types. When HL-NO(2) and [Ru(PPh(3))(3)Cl2] react in
      solution at ambient temperature, trans-[Ru(PPh(3))(2)(L-NO2Cl] is obtained. Its
      structure determination by X-ray crystallography shows that L-NO2 is coordinated
      as a tridentate C,N,O-donor ligand. When reaction between HL-NO2 and
      [Ru(PPh(3))(3)Cl2] is carried out in refluxing ethanol, a more stable cis isomer
      of [Ru(PPh(3))(2)(L-NO2)Cl] is obtained. The trans isomer can be converted to the
      cis isomer simply by providing appropriate thermal energy. Slow reaction of HL-R
      with [Ru(PPh(3))(2)(CO2)Cl2] in solution at ambient temperature yields 5
      [Ru(PPh(3))(2)(L-R)(CO)Cl] complexes. A structure determination of 5
      [Ru(PPh(3))(2)(L-NO2)(CO)Cl] shows that the semicarbazone ligand is coordinated
      as a bidentate N,O-donor, forming a five-membered chelate ring. When reaction
      between HL-R and [Ru(PPh(3))(2)(CO2Cl2] is carried out in refluxing ethanol, the
      4-[Ru(PPh(3))(2)(L-R)(CO)Cl] complexes are obtained. A structure determination of
      4-[Ru(PPh(3))(2)(L-NO2)(CO)Cl] shows that a semicarbazone ligand is bound to
      ruthenium as a bidentate N,O-donor, forming a four-membered chelate ring. All the
      complexes are diamagnetic (low-spin d(6), S = 0). The trans- and cis
      [Ru(PPh(3))(2)(L-NO2)Cl] complexes undergo chemical transformation in solution.
      The 5- and 4-[Ru(PPh(3))(2)(L-R)(CO)Cl] complexes show sharp NMR signals and
      intense MLCT transitions in the visible region. Cyclic voltammetry of the 5
      [Ru(PPh(3))(2)(L-R)(CO)Cl] and 4-[Ru(PPh(3))(2)(L-R)(CO)Cl] complexes show the
      Ru(II)-Ru(III) oxidation to be within 0.66-1.07 V. This oxidation potential is
      found to linearly correlate with the Hammett constant of the substituent R.

PMID- 11300809
TI  - Azametallacycles from Ag(I)- or Cu(II)-promoted coupling reactions of
      dialkylcyanamides with oximes at Pt(II).
AB  - The dialkylcyanamide complexes cis-[PtCl(NCNR(2))(PPh(3))(2)][BF(4)] 1 and cis
      [Pt(NCNR(2))(2)(PPh(3))(2)][BF(4)](2) 2 (R = Me or Et) have been prepared by
      treatment of a CH(2)Cl(2) solution of cis-[PtCl(2)(PPh(3))(2)] with the
      appropriate dialkylcyanamide and one or two equivalents of Ag[BF(4)],
      respectively. Compounds 2 can also be obtained from 1 by a similar procedure.
      Their reaction with oximes, HON=CR'R' ' (R'R' ' = Me(2) or C(4)H(8)), in
      CH(2)Cl(2) and in the presence of Ag[BF(4)] or Cu(CH(3)COO)(2), leads to the
      novel type of azametallacycles cis-[Pt(NH=C(ON=CR'R")-NR2)(PPh3)2][BF4]2 4 upon
      an unprecedented coupling of the organocyanamides with oximes, in a process that
      proceeds via the mixed oxime-organocyanamide species cis-[Pt(NCNR(2))(HON=CR'R'
      ')(PPh(3))(2)][BF(4)](2) 3, and is catalyzed by either Ag(+) or Cu(2+) which
      activate the ligating organocyanamide by Lewis acid addition to the amide group.
      In contrast, in the organonitrile complexes cis-[Pt(NCR)(2)(PPh(3))(2)][BF(4)](2)
      5 (R = C(6)H(4)OMe-4 or Et), obtained in a similar way as 2 (but by using NCR
      instead of the cyanamide), the ligating NCR is not activated by the Lewis acid
      and does not couple with the oximes. The spectroscopic properties of those
      complexes are reported along with the molecular structures of 2b (R = Et), 4a1 (R
      = Me, R'R' ' = Me(2)), and 4b1 (R = Et, R'R' ' = Me(2)), as established by X-ray
      crystallography which indicates that in the former complex the amide-N-atoms are
      trigonal planar, whereas in the latter (4a1 and 4b1) the five-membered rings are
      planar with a localized N=C double bond (imine group derived from the cyanamide)
      and the exocyclic amide and alkylidene groups (in 4b1) are involved in two
      intramolecular H-bonds to the oxygen atom of the ring.

PMID- 11300810
TI  - Electronic relaxation phenomena following (57)Co(EC)(57)Fe nuclear decay in
      [Mn(II)(terpy)2](ClO4)2.(1/2)H2O and in the spin crossover complexes
      [Co(II)(terpy)2]X2.nH2O (X = Cl and ClO4): a Mossbauer emission spectroscopic
      study.
AB  - The valence states of the nucleogenic (57)Fe arising from the nuclear
      disintegration of radioactive (57)Co by electron capture decay, (57)Co(EC)(57)Fe,
      have been studied by Mossbauer emission spectroscopy (MES) in the (57)Co-labeled
      systems: [(57)Co/Co(terpy)(2)]Cl(2).5H(2)O (1),
      [(57)Co/Co(terpy)(2)](ClO(4))(2).(1)/(2)H(2)O (2), and
      [(57)Co/Mn(terpy)(2)](ClO(4))(2). (1)/(2)H(2)O (3) (terpy = 2,2':6',2' '
      terpyridine). The compounds 1, 2, and 3 were labeled with ca. 1 mCi of (57)Co and
      were used as the Mossbauer sources at variable temperatures between 300 K and ca.
      4 K. [Fe(terpy)(2)]X(2) is a diamagnetic low-spin (LS) complex, independent of
      the nature of the anion X, while [Co(terpy)(2)]X(2) complexes show gradual spin
      transition as the temperature is varied. The Co(II) ion in 1 "feels" a somewhat
      stronger ligand field than that in 2; as a result, 83% of 1 stays in the LS state
      at 321 K, while in 2 the high-spin (HS) state dominates at 320 K and converts
      gradually to the LS state with a transition temperature of T(1/2) approximately
      180 K. Variable-temperature Mossbauer emission spectra for 1, 2, and 3 showed
      only LS-(57)Fe(II) species at 295 K. On lowering the temperature, metastable HS
      Fe(II) species generated by the (57)Co(EC)(57)Fe process start to grow at ca. 100
      K in 1, at ca. 200 K in 2, and at ca. 250 K in 3, reaching maximum values of 0.3
      at 20 K in 1, 0.8 at 50 K in 2, and 0.86 at 100 K in 3, respectively. The
      lifetime of the metastable HS states correlates with the local ligand field
      strength, and this is in line with the "inverse energy gap law" already
      successfully applied in LIESST relaxation studies.

PMID- 11300811
TI  - Structural and photomagnetic studies of two compounds in the system
      Cu(2+)/Mo(CN8)(4-): from trinuclear molecule to infinite network.
AB  - The syntheses and structural and physical characterization of the compounds
      [Cu(bipy)(2)](2)[Mo(CN)(8)].5H(2)O. CH(3)OH (1) with bipy = 2,2'-bipyridine and
      M(II)(2)[Mo(IV)(CN)(8)].xH(2)O (2 with M = Cu, x = 7.5; 3 with M = Mn, x = 9.5)
      are presented. 1 crystallizes in the triclinic space group P1; (a = 11.3006(4) A,
      b = 12.0886(5) A, c = 22.9589(9) A, alpha = 81.799(2) degrees, beta = 79.787(2)
      degrees, gamma = 62.873(2) degrees, Z = 2). The structure of 1 consists of
      neutral trinuclear molecules in which a central [Mo(CN8)](4-) anion is linked to
      two [Cu(bipy)2](2+) cations through two cyanide bridges. 2 crystallizes poorly,
      and hence, structural information has been obtained from the wide-angle X-ray
      scattering (WAXS) technique, by comparison with 3 and
      Fe(II)(2)(H(2)O)(4)[Mo(IV)(CN)(8)].4H(2)O whose X-ray structure has been
      previously solved. 2, 3, and Fe(II)(2)(H(2)O)(4)[Mo(IV)(CN)(8)].4H(2)O form
      extended networks with all the cyano groups acting as bridges. The magnetic
      properties have shown that 1 and 2 behave as paramagnets. Under irradiation with
      light, they exhibit important modifications of their magnetic properties, with
      the appearance at low temperature of magnetic interactions. For 1 the
      modifications are irreversible, whereas they are reversible for 2 after cycling
      in temperature. These photomagnetic effects are thought to be caused by the
      conversion of Mo(IV) (diamagnetic) to Mo(V)(paramagnetic) through a
      photooxidation mechanism for 1 and a photoinduced electron transfer in 2. These
      results have been correlated with the structural features.

PMID- 11300812
TI  - Long-range exchange interactions and integer-spin S(t) = 2 EPR spectra of a
      Cr(III)Zn(II)Cr(III) species with multiplet mixing.
AB  - Synthesis, structural, and spectroscopic characterization of the linear cationic
      complex [LCr(III)(mu-[dmg)(3)Zn(II))Cr(III)L](2+) (1) in which L = 1,4,7
      trimethyl-1,4,7-triazacyclononane and dmg is the dimethylglyoximato anion are
      reported. The Cr...Cr distance of 1 is 7 A. SQUID magnetic susceptibility
      measurements reveal the presence of long-range exchange interaction of the
      Cr(III) terminal ions, mediated by the diamagnetic Zn(II)(dmg)(3) "bridging
      ligand" (J(0) = -4.4 cm(-1), H(ex) = -2J(0)S(1)S(2), S(i) = 3/2). Multifrequency
      EPR measurements (S-, X-, Q-band) on frozen solutions were used to establish the
      intramolecular nature of the exchange coupling and to determine the zero-field
      splitting (ZFS) parameters and the anisotropic contributions of spin coupling. An
      effective spin Hamiltonian description was applied for interpretation of the
      spectra originating from the S(t) = 2 total spin manifold which included up to
      fourth-order terms for the ZFS. By the help of alternative simulations with the
      full coupling matrix for two spins S(i) = 3/2 (16 x 16) it could be shown that
      the higher-order terms in the effective description owe their origin to multiplet
      mixing due to competing single-ion ZFS (the absolute value of D(i) = 0.2 cm(-1))
      and isotropic exchange interaction. The magnetic anisotropy related to dimer
      properties could be readily explained by dipolar coupling (j(z) = -0.012 cm(-1)).
      Implications for the interpretation of other integer-spin EPR spectra are
      discussed.

PMID- 11300813
TI  - An ab initio MO study on the structures and electronic states of hydrogen-bonded
      O3- HF and SO2-HF complexes.
AB  - Ab initio molecular orbital (MO) calculations have been carried out for base
      hydrogen fluoride (HF) complexes (base = O3 and SO2) in order to elucidate the
      structures and energetics of the complexes. The ab initio calculations were
      performed up to the QCISD(T)/6-311++G(d,p) level of theory. In both complexes,
      hydrogen-bonded structures where the hydrogen of HF orients toward one of the
      oxygen atoms of bases were obtained as stable forms. The calculations showed that
      cis and trans isomers exist in both complexes. All calculations for the SO2-HF
      complex indicated that the cis form is more stable in energy than the trans form.
      On the other hand, in O3-HF complexes, the stable structures are changed by the
      ab initio levels of theory used, and the energies of the cis and trans forms are
      close to each other. From the most sophisticated calculations (QCISD(T)/6
      311++G(d,p)//QCISD/6-311+G(d) level), it was predicted that the complex formation
      energies for cis SO2-HF, trans SO2-HF, cis O3-HF, and trans O3-HF are 6.1, 5.7,
      3.4, and 3.6 kcal/mol, respectively, indicating that the binding energy of HF to
      SO2 is larger than that of O3. The harmonic vibrational frequencies calculated
      for cis O3-HF and cis SO2-HF complexes were in good agreement with the
      experimental values measured by Andrews et al. Also, the calculated rotation
      constants for cis SO2-HF agreed with the experiment.

PMID- 11300814
TI  - Synthesis and characterization of non-centrosymmetric TeSeO4.
AB  - The synthesis, crystal structure, and characterization of a non-centrosymmetric
      oxide, TeSeO4, are reported. The material was synthesized by combining TeO2 and
      SeO2 in a quartz tube and heating at 370 degrees C. TeSeO4 has a three
      dimensional structure containing [SeO(3/2)](+) cations linked to [TeO(5/2)](-)
      anions. Both the Se(4+) and the Te(4+) atoms are in asymmetric environments owing
      to their nonbonded electron pair. The material is SHG active, with a SHG
      intensity of 400 times SiO(2). Crystal data: monoclinic, space group Ia (No. 9,
      cell choice 3), with a = 4.3568(8) A, b = 12.465(3) A, c = 6.7176(15) A, beta =
      90.825(4) degrees, and Z = 4.

PMID- 11300815
TI  - Local structure and tunneling kinetics of ammonium aluminum alum by infrared hole
      burning.
AB  - The title compound, crystallized with a few percent of deuterium, contains some
      NH(3)D(+) and HOD. At low temperatures, five N-D stretch bands are observed.
      These belong to two ammonium sites with apparent C(s) symmetry in the low
      temperature phase. The N-D bands can be hole-burned with an infrared laser.
      Burning bands belonging to the A-sites transforms some of them to the higher
      energy B-sites. The A- and B-sites probably differ from each other by the
      arrangement of water and sulfate about the ammonium.

PMID- 11300816
TI  - Syntheses and structural characterization of luminescent platinum(II) complexes
      containing di-tert-butylbipyridine and new 1,1-dithiolate ligands.
AB  - Three new di-tert-butylbipyridine (dbbpy) complexes of platinum(II) (1-3)
      containing 1,1-dithiolate ligands have been synthesized and characterized. The
      1,1-dithiolates are 2,2-diacetylethylene-1,1-dithiolate (S(2)C=C(C(O)Me)2) (1), 2
      cyano-2-p-bromophenylethylene-1,1-dithiolate (S(2)C=C(CN)(p-C(6)H(4)Br)) (2), and
      p-bromophenyl-2-cyano-3,3-dithiolatoacrylate (S(2)C=C(CN)(COO-p-C(6)H(4)Br)) (3).
      Complex 1 exhibits a solvatochromic charge-transfer absorption in the 430-488 nm
      region of the spectrum and a luminescence around 635 nm in ambient temperature
      CH(2)Cl(2) solution. These observations are consistent with what has been seen
      previously in related Pt diimine 1,1-dithiolate complexes. The nature of the
      emissive state is assigned as a (3)(mixed metal/dithiolate-to-diimine) charge
      transfer, while the solvatochromic absorption band corresponds to the singlet
      transition of similar orbital character. The other complexes also exhibit a low
      energy solvatochromic absorption. The crystal structures of two of the complexes
      have been determined, representing the first time that Pt(diimine)(1,1
      dithiolate) complexes have been crystallographically studied. The structures
      confirm the expected square planar coordination geometry with distortions in bond
      angles dictated by the constraints of the chelating ligands. The Pt-S and Pt-N
      bond lengths and S-Pt-S and N-Pt-N bond angles for the two structures are
      identical within experimental error (2.283(2) and 2.278(2) A; 2.053(6) and
      2.050(8) A; 75.01(8) degrees and 75.40(8) degrees; 79.2(2) degrees and 79.0(2)
      degrees, respectively). Crystal data for 1: monoclinic, space group P2(1)/n (No.
      14), with a = 7.20480(10) A, b = 20.53880(10) A, c = 19.1072(2) A, beta = 93.83
      degrees, V = A(3), Z = 4, R1 = 3.34% (I > 2sigma(I)), wR2 = 9.88% (I > 2sigma(I))
      for 3922 unique reflections. Crystal data for 2: monoclinic, space group P2(1)/n
      (No. 14), with a = 15.0940(5) A, b = 9.5182(3) A, c = 20.4772(7) A, beta =
      111.151(1) degrees, V = A(3), Z = 4, R1 = 4.07% (I > 2sigma(I)), wR2 = 8.64% (I >
      2sigma(I)) for 3859 unique reflections.

PMID- 11300817
TI  - A donor--acceptor--donor bridging ligand in a class III mixed-valence complex.
AB  - The novel mononuclear and dinuclear complexes [Ru(trpy)(bpy)(apc)][PF(6)] and
      [(Ru(trpy)(bpy))(2)(mu-adpc)][PF(6)](2) (bpy = 2,2'-bipyridine, trpy = 2,2':6',2'
      '-terpyridine, apc(-) = 4-azo(phenylcyanamido)benzene, and adpc(2)(-) = 4,4'
      azodi(phenylcyanamido)) were synthesized and characterized by (1)H NMR, UV-vis,
      and cyclic voltammetry. Crystallography showed that the dinuclear Ru(II) complex
      crystallizes from diethyl ether/acetonitrile solution as [(Ru(trpy)(bpy))(2)(mu
      adpc)][PF(6)](2).2(acetonitrile).2(diethyl ether). Crystal structure data are as
      follows: crystal system triclinic, space group P1, with a, b, and c = 12.480(2),
      13.090(3) and 14.147(3) A, respectively, alpha, beta, and gamma = 79.792(3),
      68.027(3), and 64.447(3) degrees, respectively, V = 1933.3(6) A(3), and Z = 1.
      The structure was refined to a final R factor of 0.0421. The mixed-valence
      complex with metal ions, separated by a through-space distance of 19.5 A, is a
      class III system, having the comproportionation constant K(c) = 1.3 x 10(13) and
      an intervalence band at 1920 nm (epsilon(max) = 10 000 M(-1) cm(-1)), in
      dimethylformamide solution. The results of this study strongly suggest that the
      bridging ligand adpc(2-) can mediate metal-metal coupling through both hole
      transfer and electron-transfer superexchange mechanisms.

PMID- 11300818
TI  - Crystal structure analysis and chiral recognition study of Delta
      [Ru(bpy)2(py)2][(+)-O,O'-dibenzoylD-tartrate].12H2O and Lambda-[Ru(bpy)2(py)2][(
      )-O,O'-dibenzoyl-L-tartrate].12H2O.
AB  - The molecular structure and crystal-packing mode of the enantiopure chiral
      building blocks Delta-[Ru(bpy)(2)(py)(2)][(+)-O,O'-dibenzoyl-D-tartrate].12H(2)O
      (I) and Lambda-[Ru(bpy)(2)(py)(2)][(-)-O,O'-dibenzoyl-L-tartrate].12H(2)O (II)
      have been determined by single-crystal X-ray diffraction data. This study
      proposes a model of how the L- and D-dibenzoyltartrate anions recognize the
      chirality of the hydrophobic [Ru(bpy)(2)(py)(2)](2+) complex. The monoclinic unit
      cell contains four complex cations, four tartrate anions, and 48 water molecules.
      Since there are no possibilities to form hydrogen bonds between the cations and
      anions, chiral recognition is due to crystal packing. Two benzoyl rings of two
      different tartrate anions are gripping the two bpy-planes of the Ru-complex.
      Further a third benzoyl ring from a tartrate anion is packed between the two
      pyridine rings, favoring one enantiomeric form to crystallize from aqueous
      solution. Crystal structure data for I at 153 K: a = 15.342(3) A, b = 19.200(4)
      A, c = 18.872(4) A, beta = 104.841(3) degrees, monoclinic space group C(2), R(1)=
      0.0239 (I > 2sigma(I)), R(2) = 0.0606, Flack parameter = 0.0115 (with esd
      0.0166). For II at 293 K: a = 15.376(4) A, b = 19.388(11) A, c = 19.085(7) A,
      beta = 105.11(2) degrees, monoclinic space group C121, R(1)= 0.0686 (I >
      2sigma(I)), R(2) = 0.1819, Flack parameter = -0.0100 (with esd 0.0521).

PMID- 11300819
TI  - Structures of a tetradentate ferrocenyl ligand and its oxorhenium(V) complex in
      solution and in the solid state.
AB  - The novel ferrocenyl ligand rac-1,6-diferrocenyl-N,N'-bis(2-hydroxypropyl)-2,5
      diazahexane (1, H(2)L) was synthesized from ferrocenylcarboxaldehyde and
      ethylenediamine followed by the reduction of the Schiff base with LiAlH(4) and
      subsequent N-alkylation with 1,2-propyleneoxide. The dianion of H(2)L reacted
      with [ReO(PPh(3))(2)Cl(3)], and the product was treated with NH(4)PF(6) to afford
      the complex [ReO(L-N(2)O(2))PPh(3)]PF(6) (2). Both the ferrocenyl ligand and the
      complex were characterized in solution by NMR spectroscopy and in the solid state
      by single-crystal X-ray diffraction studies. NMR investigations reveal two
      solvent-dependent isomers for the ferrocenyl ligand in solution of which the
      major form is the more ordered one. The cation of 2 displays a nonsymmetrically
      coordinated N(2)O(2) ligand.

PMID- 11300820
TI  - Syntheses of chromium pentacarbonyl derivatives of arsenic(V) and antimony(V).
      contrasting chemical reactivity with organic halogen derivatives.
AB  - We have synthesized a new series of chromium-group 15 dihydride and hydride
      complexes [H(2)As(Cr(CO)(5))(2)](-) (1) and [HE(Cr(CO)(5))(3)](2)(-) (E = As, 2a;
      E = Sb, 2b), which represent the first examples of group 6 complexes containing E
      H fragments. The contrasting chemical reactivity of 2a and 2b with organic
      halogen derivatives is demonstrated. The reaction of 2a with RBr (R = PhCH(2), HC
      triple bond CCH(2)) produces the RX addition products [(R)(Br)As(Cr(CO)(5))(2)](
      ) (R = PhCH(2), 3; R = C(3)H(3), 4), while the treatment of 2b with RX (RX =
      PhCH(2)Br or HC triple bond CCH(2)Br, CH(3)(CH(2))(5)C(O)Cl) forms the halo
      substituted complexes [XSb(Cr(CO)(5))(3)](2-) (X = Br, 5; X = Cl, 6). Moreover,
      the dihaloantimony complexes [XX'Sb(Cr(CO)(5))(2)](-) can be obtained from the
      reaction of 2b with the appropriate organic halides. In this study, a series of
      organoarsenic and antimony chromium carbonyl complexes have been synthesized and
      structurally characterized and the role of the main group on the formation of the
      resultant complexes is also discussed.

PMID- 11300822
TI  - Unusual spin state equilibrium of azide metmyoglobin induced by ferric
      corrphycene.
AB  - Myoglobin was reconstituted with the ferric complex of corrphycene, a novel
      porphyrin isomer with a rearranged tetrapyrrole array, to investigate the
      influence of porphyrin deformation on the equilibrium between high-spin (S = 5/2)
      and low-spin (S = 1/2) states in the azide derivative. The azide affinity, 2.5 x
      10(4) M(-1), was 1 order of magnitude lower than the corresponding values of a
      reference myoglobin containing an electron-deficient diformylheme similar to the
      corrphycene. Analysis of the visible absorption spectrum over a range of 0-40
      degrees C reveals that the population of high-spin iron is 76-82% at room
      temperature for azide metmyoglobin complexed with ferric corrphycene. The unusual
      predominance of the high-spin state was verified from the infrared spectrum of
      coordinating azide, where the high-spin peak at 2046 cm(-1) is 4-fold larger in
      intensity than the 2023 cm(-1) low-spin band. Electron paramagnetic resonance at
      15 K further indicated that the iron-histidine bond is cleaved to form a five
      coordinate derivative in some fraction of the myoglobin. The remarkable high-spin
      bias of the spin equilibrium at room temperature and cleavage of the iron
      histidine bond at 15 K could be explained in terms of the contracted and
      trapezoidal metallo core that weakens the iron-histidine bond of azide
      metmyoglobin bearing corrphycene.

PMID- 11300821
TI  - Photochemical generation of cyclopentadienyliron dicarbonyl anion by a
      nicotinamide adenine dinucleotide dimer analogue.
AB  - Irradiation of the absorption band of an NAD (nicotinamide adenine dinucleotide)
      dimer analogue, 1-benzyl-1,4-dihydronicotinamide dimer, (BNA)(2), in acetonitrile
      containing a cyclopentadienyliron dicarbonyl dimer, [CpFe(CO)(2)](2), results in
      generation of 2 equiv of the cyclopentadienyliron dicarbonyl anion,
      [CpFe(CO)(2)](-), accompanied by the oxidation of (BNA)(2) to yield 2 equiv of
      BNA(+). The studies on the quantum yields, the electrochemistry, and the
      transient absorption spectra have revealed that the photochemical generation of
      [CpFe(CO)(2)](-) by (BNA)(2) proceeds via photoinduced electron transfer from the
      triplet excited state of (BNA)(2) to [CpFe(CO)(2)](2).

PMID- 11300823
TI  - Hydrogen impurity effects. A(5)Tt(3)Z intermetallic compounds between A = Ca, Sr,
      Ba, Eu, Yb and Tt = Sn, Pb with Cr(5)B(3)-like structures that are stabilized by
      hydride or fluoride (Z).
AB  - The binary systems Ca-Sn, Ba-Sn, Eu-Sn, Yb-Sn, Sr-Pb, Ba-Pb, and Eu-Pb do not
      contain Cr(5)B(3)-like A(5)Tt(3) phases when care is taken to exclude hydrogen
      from the reactions (Tt = tetrel, Si-Pb). All form ternary A(5)Tt(3)H(x)() phases
      (x < or = 1) with "stuffed" Cr(5)B(3)-like structures instead, and all of those
      tested, Ca-Sn, Ba-Sn, Sr-Pb, and Ba-Pb, also yield the isostructural A(5)Tt(3)F.
      The structures and compositions of Ca(5)Sn(3)H(x), Ca(5)Sn(3)F(0.89),
      Eu(5)Sn(3)H(x), and Sr(5)Pb(3)F have been refined from single-crystal X-ray
      diffraction data and of Ca(5)Sn(3)D from powder neutron data. The interstitial H,
      F atoms are bound in a tetrahedral (A(2+))(4) cavity in a Cr(5)B(3)-type metal
      atom structure. Nine previous reports of binary "Ba(5)Sn(3)", "Yb(5)Sn(3)",
      "Sr(5)Pb(3)", and "Ba(5)Pb(3)" compounds were wrong and presumably concerned the
      hydrides. The new ternary phases are generally Pauli-paramagnetic, evidently with
      pi electrons from the characteristic tetrelide dimers in this structure type at
      least partially delocalized into the conduction band. The Sn-Sn bonds appear
      correspondingly shortened on oxidation. Other new phases reported are CaSn (CrB
      type), Yb(5)Sn(4)H(x) (Sm(5)Ge(4)), YbSn ( approximately TlTe), Ba(5)Pb(3) (
      approximately W(5)Si(3)), and Yb(31)Pb(20) (Ca(31)Sn(20)).

PMID- 11300824
TI  - The simplest supramolecular complexes containing pairs of Mo(2)(formamidinate)(3)
      units linked with various dicarboxylates: preparative methods, structures, and
      electrochemistry.
AB  - Twelve compounds containing two quadruply bonded Mo(2)(DAniF)(3) (DAniF = N,N'-di
      p-anisylformamidinate) units linked by dicarboxylate anions have been prepared in
      high purity and good yields. All of these compounds have been characterized by
      crystallography and NMR. The dinuclear pairs display electrochemical behavior
      which is controlled by the nature of the bridging dicarboxylate group. As
      described by the linkers, the compounds are oxalate, 1; acetylene dicarboxylate,
      2; fumarate, 3; tetrafluorophthalate, 4; carborane dicarboxylate, 5; ferrocene
      dicarboxylate, 6; malonate, 7; succinate, 8; propane-1,3-dicarboxylate, 9;
      tetrafluorosuccinate, 10; bicyclo[1.1.1]pentane-1,3-dicarboxylate, 11; and trans
      1,4-cyclohexanedicarboxylate, 12.

PMID- 11300825
TI  - Nmr study of the solution structures of TcO(2)F(3) and ReO(2)F(3).
AB  - Both TcO(2)F(3) and ReO(2)F(3) are infinite chain, fluorine-bridged polymers in
      the solid state. Their solution structures have been studied by (19)F and (99)Tc
      NMR spectroscopy in SO(2)ClF solution and shown to exhibit cyclic (MO(2)F(3))(3)
      (M = Tc, Re) and (ReO(2)F(3))(4) structures that have been confirmed by
      simulation of the (19)F NMR spectra. The trimers dominate in both the technetium
      and rhenium systems, with both the tetramer and trimer existing in equilibrium in
      the rhenium system. A low concentration of a higher, possibly pentameric, cyclic
      rhenium polymorph is also present in equilibrium with the trimer and tetramer.

PMID- 11300826
TI  - Decomposition of alkyl-substituted urea molecules at a hydroxide-bridged dinickel
      center.
AB  - The interactions between N-methylurea, N,N'-dimethylurea, N,N-dimethylurea,
      tetramethylurea, and thiourea and the hydroxide-bridged dinickel complex
      [Ni(2)(mu-OH)(mu-H2O)(bdptz)(H2O2](OTs)(3) were investigated. Structural
      characterization of [Ni(2)(mu-OH)(mu-H2O)(bdptz)(Me-urea)(CH3CN)](ClO4)(3) (1)
      and [Ni(2)(mu-OH)(mu-H2O)(bdptz)(thiourea)(CH3CN)](ClO4)(3) (2) provided insight
      into the interactions of the substrates with the dinickel center. In 1, the
      methylurea molecule coordinates to the dinickel complex through its carbonyl
      oxygen atom. Complex 2 has a similar geometry, with the thiourea molecule bound
      to a nickel ion through its sulfur atom. When the urea substrates are heated in
      the presence of the hydroxide-bridged dinickel complex, N-methylurea and N,N
      dimethylurea react to form methylammonium cyanate and dimethylammonium cyanate,
      respectively. After long reaction times, thiourea reacts similarly, producing
      ammonium thiocyanate. The other substrates are unreactive. These results indicate
      that the dinickel complex promotes the elimination of alkylamines from urea
      substrates to form cyanate but cannot effect the direct hydrolysis of such
      substrates.

PMID- 11300827
TI  - Tuning the metal-metal bonds in the linear tricobalt compound Co3(dpa)(4)Cl2:
      bond-stretch and spin-state isomers.
AB  - Sixteen crystal structures have been determined for the Co3(dpa)(4)Cl2 (1)
      molecule in the following five crystalline solvates: 1.0.85(C2H5)(2)O.0.15CH2Cl2
      (at 120, 213, 296 K); 1.C(4)H(8)O (at 120, 295 K); 1.C(6)H(6) (at 170, 213, 260,
      316 K); 1.C(6)H(12) (at 120, 213, 295 K); and 1.1.75C(7)H(8).0.5C(6)H(14) (at 90,
      110, 170, 298 K). For 1.0.85(C(2)H(5))(2)O.0.15CH2Cl2 the molecule of 1 is almost
      symmetrical at 120 K (Co-Co distances of 2.3191(3) and 2.3304(3) A) and remains
      so at 296 K (2.2320(3) and 2.3667(4) A). For 1.C(4)H(8)O the Co(3) chain is
      precisely symmetric at both 120 and 295 K though the Co-Co distances increase
      from 2.3111(4) to 2.3484(4) A as the temperature rises. Compound 1.C(6)H(6) is
      isomorphous with 1.C(4)H(8)O at 213 and 295 K and has rigorously symmetrical
      molecules at these two temperatures. Between 213 and 120 K the space group
      changes from Pccn to P2(1)/c, so that a symmetrical arrangement is no longer
      required and the two Co-Co distances then differ slightly (by 0.013 A). For
      1.C(6)H(6) there is a phase change between 316 K (Pca2(1)) and 260 K (Pna2(1)).
      At all four temperatures, however, the molecule is almost symmetrical, with the
      two independent Co-Co distances never differing by more than 0.026 A.
      1.1.75C(7)H(8).0.5C(6)H(14) contains, at all temperatures between 90 and 298 K,
      two crystallographically independent molecules, each of which is distinctly
      unsymmetrical at 298 K (Co-Co distances of 2.312(2) and 2.442(2) A for one and
      2.310(2) and 2.471(2) for the other). In the first of these the distances
      converge to a much smaller separation (0.056 A) at 90 K while in the second the
      difference decreases to only 0.006 A at 90 K. Magnetic susceptibility
      measurements from 1.8 to 350 K indicate in each case that a gradual spin
      crossover, from a doublet to a quartet state, occurs over this temperature range.

PMID- 11300828
TI  - Compounds with symmetrical tricobalt chains wrapped by dipyridylamide ligands and
      cyanide or isothiocyanate ions as terminal ligands.
AB  - Three new linear compounds of the type Co(3)(dpa)(4)X(2), where dpa is the anion
      of di(2-pyridyl)amine and X is NCS(-) (5), CN(-) (6), and N(CN)(2)(-) (7), have
      been prepared, and their structures and magnetic behavior have been studied. In
      all of them, including three different solvates of 5, the Co(3) chains are
      symmetrical with Co-Co distances of ca. 2.31-2.32 A. The appearance of four lines
      in the (1)H NMR spectra of the three compounds is also consistent with a
      symmetrical structure in solution. For all compounds, the magnetic behavior is
      quite similar with mu(eff) of ca. 1.9-2.0 micro(B) at temperatures between 1.8
      and 200 K. As the temperature increases, the effective moments increase
      gradually, but since saturation is not reached, even at 400 K, the high-spin
      state cannot be assigned.

PMID- 11300829
TI  - The effect of pH on the dimensionality of coordination polymers.
AB  - Hydrothermal reactions of simple alkaline salts or their hydroxides with 3,5
      pyrazoledicarboxylic acid (H(3)pdc) yielded seven new compounds. At a lower pH
      level three one-dimensional structures [Ca(Hpdc)(H(2)O)(4)].2H(2)O (1),
      [Ca(Hpdc)(H(2)O)(4)].H(2)O (2), and [Ba(H(2)pdc)(2)(H(2)O)(4)].2H(2)O (6) were
      obtained by evaporation of the solutions resulting from hydro(solvo)thermal
      reactions of MCl(2) (M = Ca, Ba) with H(3)pdc in water (1, 6) or in water/Et(3)N
      (2) at 150 degrees C for 3 days. Crystal structures of 1 and 2 contain zigzag
      chains of metal centers bridged by a single Hpdc(2-) ligand, whereas structure 6
      consists of linear chains of metal centers bridged by two H(2)pdc(-) ligands. A
      dimer molecule [Sr(H(3)pdc)(H(2)pdc)(2)(H(2)O)(3)](2).2(H(3)pdc).4H(2)O (4) was
      obtained from a similar hydrothermal reaction using Sr(ClO(4))(2).6H(2)O instead
      of MCl(2). This compound contains [2+2] metallomacrocycles. At higher pH levels
      (pH = 4-6), the three-dimensional polymers [M(Hpdc)(H(2)O)] (Ca 3, Sr 5, Ba 7 )
      were isolated by reactions of MCl(2) (M = Ca, Sr, Ba) with H(3)pdc in
      water/Et(3)N or in M(OH)(2) (M = Ca, Sr, Ba) with H(3)pdc in water under
      hydro(solvo)thermal conditions (150 degrees C, 3 days). Calcium and strontium are
      seven- and nine-coordinated in 3 and 5, respectively; barium is nine- and ten
      coordinated in 7. It was observed that the increase in pH resulted in a higher
      connectivity level of ligands, which in turn leads to a higher dimensionality of
      the crystal structures. The correlation between the structures and pH values will
      be discussed. Crystal data: for 1, monoclinic, space group P2(1)/n (No. 14), with
      a = 8.382(2), b = 12.621(3), c = 11.767(2) A, beta = 98.91(3) degrees, Z = 4; for
      2, 3, and 5, monoclinic, space group P2(1)/c (No. 14), Z = 4, a = 7.711(2), b =
      15.574(3), c = 9.341(2) A, beta = 96.73(3) degrees, Z = 4 (2), a = 6.616(1), b =
      12.654(3), c = 8.782(2) A, beta = 103.65(3) degrees, Z = 4 (3), a = 9.213(2), b =
      12.088(3), c = 6.196(2) A, beta = 98.96(3) degrees (5); for 4 and 7, triclinic,
      space group P1 (No. 2), with a = 11.263(2), b = 11.460(3), c = 12.904(2) A, alpha
      = 71.54(3), beta = 98.96(3), gamma = 89.03(3) degrees, Z = 1 (4), a = 7.107(1), b
      = 9.780(2), c = 11.431(2) A, alpha = 74.69(3), beta = 73.39(3), gamma = 85.29(3)
      degrees, Z = 2 (7); for 6, monoclinic, space group C2/c (No. 15), with a =
      20.493(4), b = 6.708(1), c = 15.939(3) A, beta = 123.56(3) degrees, Z = 4.

PMID- 11300830
TI  - NMR studies of heteropolyanion [P(2)W(20)O(70)(H2O)2](-10) complexes with metal
      cations.
AB  - We have used multinuclear NMR and IR spectroscopy to study the interaction of a
      number of metal cations with monovacant heteropolyanion
      [P(2)W(20)O(7)(0)(H(2)O)(2)](10)(-) (P(2)W(20)) in aqueous solutions starting
      from its K salt. We have also prepared and studied P(2)W(20) in an Na-only
      medium. The observed differences in the NMR spectra of NaP(2)W(20)and
      KP(2)W(20)solutions and the importance of K(+) and Na(+) for the formation of
      P(2)W(20) suggest that this polyanion exists only as a complex with the alkaline
      cations. When both cations were simultaneously present in solution, we observed
      the broadening of the NMR signals of P(2)W(20)due to the Na-K exchange. Li(+)
      does not replace K(+) or Na(+) in such complexes, and in an Li-only medium
      P(2)W(20) does not form. Of all the M(n)(+) cations studied (Pd(2+), Bi(3+),
      Sn(4+), Zr(4+), Ce(4+), Ti(4+), V(5+), and Mo(6+)) only Bi(3+), Sn(4+), and
      Ce(4+) form complexes with P(2)W(20) in strongly acidic solutions. The (183)W and
      (119)Sn NMR data suggest that Sn(4+) forms in solution two mutually
      interconvertable P(2)W(20)Sn complexes of the composition
      P(2)W(20)O(70)(H(2)O)(3)SnOH(7)(-) and (P(2)W(20)O(70)(H(2)O)(3)Sn)(2)O(14)(-)
      while Bi(3+) forms one complex of the proposed composition
      P(2)W(20)O(70)(H(2)O)(2)Bi.(7)(-) We obtained complexes with Bi and Sn as free
      heteropoly acids and studied their thermostability in the solid state.

PMID- 11300831
TI  - Dodecamethyl-closo-dodecaborate(2-).
AB  - Bis(tetraethylammonium) dodecamethyl-closo-dodecaborate(2-), [NEt(4)](2)[closo
      B(12)Me(12)], [NEt(4)](2)2, was prepared employing modified Friedel-Crafts
      reaction conditions from [NEt(4)](2)[closo-B(12)H(12)], [NEt(4)](2)1,
      trimethylaluminum, and methyl iodide. The [NEt(4)](2)2 salt provides sufficient
      solubility in water to allow the synthesis of the important alkali metal salts
      A(2)2 (A = Li, Na, K, Rb, Cs) using cation-exchange procedures. The solid state
      structure of colorless [AsPh(4)](2)2 reveals a nearly perfect icosahedral B(12)
      cluster with B-B bonds ranging from 1.785(3) to 1.807(3) A and B-C bonds of
      1.597(3)-1.625(3) A. In contrast, the crystal structure of dark-red [Py(2)CH(2)]2
      (obtained from [NEt(4)](2)2 and [Py(2)CH(2)]Br(2)) contains a distorted
      icosahedral dianion [B-B = 1.740(13)-1.811(14) A, B-C = 1.591(13)-1.704(13) A].
      In the [Py(2)CH(2)]2 salt, the dianion 2(2-) and its dipositive
      dipyridiniomethane counterion form a red charge-transfer complex. One-electron
      oxidation of 2(2)(-) by ceric(IV) ammonium nitrate affords the blue, air-stable
      radical [hypercloso-B(12)Me(12)](*-), dodecamethyl-hypercloso-dodecaborate(1-),
      2(*-), isolated as the PPN salt. X-ray crystallography reveals that the
      geometries of the B(12) clusters observed in hypercloso-[PPN]2 and closo
      [AsPh(4)](2)2 are identical and essentially undistorted icosahedra. The anion in
      the [PPN]2 structure contains B-B bonds ranging from 1.784(8) to 1.806(7) A and a
      range of B-C bonds from 1.596(7) to 1.616(7) A.

PMID- 11300832
TI  - Determination of the structures of antiinflammatory copper(II) dimers of
      indomethacin by multiple-scattering analyses of X-ray absorption fine structure
      data.
AB  - Copper K-edge X-ray absorption spectroscopic (XAS) measurements were recorded for
      the veterinary antiinflammatory Cu(II) complexes of indomethacin (1-(4
      chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid = IndoH), of the
      general formula [Cu(2)(Indo)(4)L(2)] (L = N,N-dimethylformamide (DMF), N,N
      dimethylacetamide (DMA), N-methylpyrrolidone (NMP), and water), and
      [Cu(2)(OAc)(4)(OH(2))(2)] at room temperature and 10 K. The bond lengths and
      bridging O-C-O angles of the dimeric Cu(II) cage (Cu(2)O(10)C(8)) obtained from
      the multiple-scattering (MS) fitting of the X-ray absorption fine structure
      (XAFS) using a centrosymmetric model of [Cu(2)(Indo)(4)(DMF)(2)] gave Cu.Cu =
      2.62(2) A, mean Cu-O(Ac) = 1.95(2) A, Cu-O(L) = 2.15(2) A, bridging O-C-O =
      125(1) degrees, Cu displacement from plane 0.19 A compared with the XRD data
      Cu.Cu = 2.630(1) A, mean Cu-O(Ac) = 1.959 A, Cu-O(L) = 2.143(5) A, bridging O-C-O
      angles = 123.2(5) degrees, Cu displacement from plane 0.20 A. The excellent
      agreement between the XAFS- and XRD-derived data allowed the structures of
      related [Cu(2)(Indo)(4)L(2)] (L = DMA, NMP) complexes to be determined. All
      display a similar Cu(2)O(10)C(8) coordination geometry, which is independent of
      the nature of the axial ligand. While XAFS analysis of [Cu(2)(Indo)(4)(OH(2))(2)]
      and [Cu(2)(OAc)(4)(OH(2))(2)] indicates a coordination geometry similar to that
      of [Cu(2)(Indo)(4)L(2)] (L = DMF, DMA, NMP), removal of symmetry restraints in
      the MS model is required to obtain axial bond lengths comparable to those derived
      in the XRD structures of the acetate complex. For the Indo complex, the fitted
      bond lengths with the lower symmetry model give a mean Cu-L(OH2) bond distance
      within experimental errors of the value for [Cu(2)(Indo)(4)(DMSO)(2)] (2.16(2) A)
      (XRD). The difficulty in refining the Cu-O(OH2) distance of
      [Cu(2)(OAc)(4)(OH(2))(2)] and [Cu(2)(Indo)(4)(OH(2))(2)] using a centrosymmetric
      MS model is attributed to a symmetry reduction due to hydrogen-bonding effects
      characteristic of the aqua adducts, as is observed in the XRD structure of the
      acetate complex.

PMID- 11300833
TI  - Structure of the SO(2)F(-) anion, a problem case.
AB  - Recently, room-temperature crystal structures of SO(2)F(-) in its K(+) and Rb(+)
      salts were published in Z. Anorg. Allg. Chem. 1999, 625, 385 and claimed to
      represent the first reliable geometries for SO(2)F(-). However, their almost
      identical S-O and S-F bond lengths and O-S-O and O-S-F bond angles are in sharp
      contrast to the results from theoretical calculations. To clarify this
      discrepancy, the new [(CH(3))(2)N](3)SO(+) and the known [N(CH(3))(4)(+)],
      [(CH(3))(2)N](3)S(+), and K(+) salts of SO(2)F(-) were prepared and their crystal
      structures studied at low temperatures. Furthermore, the results from previous
      RHF and MP2 calculations were confirmed at the RHF, B3LYP, and CCSD(T) levels of
      theory using different basis sets. It is shown that all the SO(2)F(-) salts
      studied so far exhibit varying degrees of oxygen/fluorine and, in some cases,
      oxygen-site disorders, with [(CH(3))(2)N](3)SO(+)SO(2)F(-) at 113 K showing the
      least disorder with r(S-F) - r(S-O) = 17 pm and angle(O-S-O) - angle(F-S-O) = 6
      degrees. Refinement of the disorder occupancy factors and extrapolation of the
      observed bond distances for zero disorder resulted in a geometry very close to
      that predicted by theory. The correctness of the theoretical predictions for
      SO(2)F(-) is further supported by the good agreement between the calculated and
      the experimentally observed vibrational frequencies and their comparison with
      those of isoelectronic ClO(2)F. A normal coordinate analysis of SO(2)F(-)
      confirms the weakness of the S-F bond with a stretching force constant of only
      1.63 mdyn/A and shows that there is no highly characteristic S-F stretching mode.
      The S-F stretch strongly couples with the SO(2) deformation modes and is
      concentrated in the two lowest a' frequencies.

PMID- 11300834
TI  - Electron transfer. 147. Reductions with gallium(I).
AB  - Solutions 0.03-0.05 M in gallium(I) can be generated by treatment of the "mixed"
      halide Ga(I)Ga(III)Cl(4) with cold water under argon and then removing the
      precipitated metallic gallium and Ga(OH)(3) by centrifugation. Ga(I) is lost from
      such preparations with a half-life of about 3 h at 0 degrees C. These solutions,
      which may be handled by conventional techniques, readily reduce I(3)(-),
      IrCl(6)(2)(-), Fe(bipy)(3)(3+), Fe(NCS)(2+), aquacob(III)alamin, and a group of
      ring-substituted derivatives of Ru(NH(3))(5)(py)(3+) but are inert to
      (NH(3))(5)CoCl(2+) and (NH(3))(5)CoBr(2+). All reactions give Ga(III). Reduction
      of HCrO(4)(-) in 2-ethyl-2-hydroxybutanoate buffers (pH 3.6) yields a Cr(IV)
      chelate of the buffering anion but forms Cr(III) when carried out in 0.01 M H(+).
      Reactions of le(-) oxidants proceed via successive single changes with the
      conversion Ga(II) --> Ga(III) much more rapid than Ga(I) --> Ga(II). Only for the
      reactions of I(3)(-) and Fe(NCS)(2+) is there evidence for redox bridging.

PMID- 11300835
TI  - Novel aluminum hydride derivatives from the reaction of H(3)Al.NMe(3) with the
      cyclosilazanes.
AB  - The amine hydrogen atoms of the cyclic trimeric silazane [Me(2)SiNH](3) are
      readily replaced by the H(2)Al. NMe(3) group in a simple aminolyis reaction of
      [Me(2)SiNH](3) with H(3)Al.NMe(3) to afford the aluminum amides
      (Me(2)SiNAlH(2).NMe(3))(n)(Me(2)SiNH)(3-n) (1, n = 3; 2, n = 1; 4, n = 2). The
      monosubstituted amide 2 could not be isolated, because it undergoes condensation
      to the tricyclic compound 1,1',2,2'-(HAlNMe(3))(2) (3). Contrary to these results
      the analogous reactions of the more flexible cyclic tetrameric silazane
      [Me(2)SiNH](4) with H(3)Al.NMe(3) did not give simple aluminum amides, but
      complicated mixtures were obtained from which the interesting polycyclic species
      Al(5)C(22)H(73)N(10)Si(8).C(6)H(6) (5) and Al(6)C(22)H(76)N(10)Si(8).1/4
      C(6)H(14) (6) could be isolated in low yields. A key step in the formation of 5
      and 6 is a low-temperature dehydrosilylation reaction which leads to cleavage of
      the silazane ring. Compounds 1, 3, and 4 were characterized spectroscopically
      ((1)H, (13)C, (27)Al NMR and FTIR) and by single crystal X-ray diffraction,
      whereas 5 and 6 were characterized by X-ray diffraction only. Thermolysis
      experiments involving 1 and 3 indicate that the onset of Al-N bond formation via
      dehydrosilylation is accompanied by loss of trimethylamine and formation of
      larger aggregates, which are stable to further silane elimination to at least 620
      degrees C.

PMID- 11300836
TI  - Kinetics and mechanism of phosphine autoxidation catalyzed by imidorhenium(V)
      complexes.
AB  - The relative binding abilities of PY(3) (PMe(3), PMe(2)Ph, PMePh(2), PPh(3),
      P(OMe)(3), P(OMe)(2)Ph, PEt(3), P(OEt)(3), P(OEt)Ph(2), and dmpe) toward Re(V)
      were evaluated. The equilibrium constants for the reactions,
      MeRe(NAr)(2)[P(OMe)(3)](2) + PY(3) = MeRe(NAr)(2)(PY(3))(2) (1) + P(OMe)(3),
      decrease in the order PMe(3) > dmpe > PMe(2)Ph > P(OMe)(2)Ph approximately PEt(3)
      > P(OEt)(3) > PMePh(2) > P(OEt)Ph(2) > PPh(3). Both electronic and steric factors
      contribute to this trend. The equilibrium constant increases as the basicity of
      PY(3) increases when the steric demand is the same. However, steric effects play
      a major role in the coordination, and this is the reason that the affinity of
      PEt(3) toward Re(V) is less than that of PMe(2)Ph. A mixed-ligand complex,
      MeRe(NAr)(2)[P(OMe)(3)](PY(3)), was also observed in the course of the stepwise
      formation of 1. The large coupling constant, (2)J(PP) > or = 491 Hz, between the
      two phosphorus atoms suggests a trans geometry for the phosphines. Compound 1
      catalyzes the oxidation of PY(3) by molecular oxygen. Kinetic studies suggest
      that the reaction of 1 with O(2) is first-order with respect to [O(2)] and
      inverse-first-order with respect to [PY(3)]. A mechanism involving a
      peroxorhenium intermediate MeRe(NAr)(2)(eta(2)-O(2)) is proposed for the
      catalytic processes. The reactivity of MeRe(NAr)(2)(eta(2)-O(2)) toward triaryl
      phosphines parallels that of the known compound MeReO(2)(eta(2)-O(2)).

PMID- 11300837
TI  - Schiff base complexes of vanadium(III, IV, V) as catalysts for the
      electroreduction of O2 to H2O in acetonitrile.
AB  - Fifteen Schiff base ligands were synthesized and used to form complexes with
      vanadium in oxidation states III, IV, and V. Electrochemical and spectral
      characteristics of the complexes were evaluated and compared. In acidified
      solutions in acetonitrile the vanadium(IV) complexes undergo reversible
      disproportionation to form V(III) and V(V) complexes. With several of the ligands
      the V(III) complexes are much more stable in the presence of acid than is the
      previously studied complex with salen, an unelaborated Schiff base ligand (H(2)
      salen = N,N'-ethylenebis(salicylideneamine)). Equilibrium constants for the
      disproportionation were evaluated. The vanadium(III) complexes reduce dioxygen to
      form two oxo ligands. The reaction is stoichiometric in the absence of acid, and
      second-order rate constants were evaluated. In the presence of acid some of the
      complexes investigated participate in a catalytic electroreduction of dioxygen.

PMID- 11300838
TI  - Highly energetic tetraazidoborate anion and boron triazide adducts.
AB  - The first crystal structures of the highly energetic tetraazidoborate anion and
      boron triazide adducts with quinoline and pyrazine as well as of
      tetramethylpiperidinium azide have been determined. Synthesis procedures and
      thorough characterization by spectroscopic methods of these hazardous materials
      are given. Quantum chemical calculations were carried out for B(N(3))(4)(-),
      B(N(3))(3), C(5)H(5)N.B(N(3))(3), (N(3))(3)B.NC(4)H(4)N.B(N(3))(3), and the
      hypothetical C(3)H(3)N(3).[B(N(3))(3)](3) at HF, MP2, and B3-LYP levels of
      theory. The structure of tetraazidoborate was optimized to S(4) symmetry and
      confirmed the results obtained from the X-ray diffraction analysis. The
      dissociation enthalpies for the pyridine (model for quinoline) as well as for the
      pyrazine adduct were calculated. For pyridine-boron triazide a value of 10.0 kcal
      mol(-1) (for pyrazine-bis(boron triazide) an average of 2.35 kcal mol(-1) per BN
      unit) was obtained.

PMID- 11300839
TI  - Rb(4)Hg(5)(Te(2))(2)(Te(3))(2)Te(3), [Zn(en)3](4)In(16)(Te2)4(Te3)Te22, and
      K2Cu2(Te2)(Te3): novel metal polytellurides with unusual metal-tellurium
      coordination.
AB  - Three novel metal polytellurides Rb(4)Hg(5)(Te(2))(2)(Te(3))(2)Te(3) (I),
      [Zn(en)(3)](4)In(16)(Te(2))(4)(Te(3))Te(22) (II), and K(2)Cu(2)(Te(2))(Te(3))
      (III) have been prepared by solvothermal reactions in superheated ethylenediamine
      at 160 degrees C. Their crystal structures have been determined by single-crystal
      X-ray diffraction techniques. Crystal data for I: space group Pnma, a = 9.803(2)
      A, b = 9.124(2) A, c = 34.714(7) A, Z = 4. Crystal data for II: space group C2/c,
      a = 36.814(7) A, b = 16.908(3) A, c = 25.302(5) A, beta = 128.46(3) degrees, Z =
      4. Crystal data for III: space group Cmcm, a = 11.386(2) A, b = 7.756(2) A, c =
      11.985(2) A, Z = 4. The crystal structure of I consists of 1D infinite ribbons of
      [Hg(5)(Te(2))(2)(Te(3))(2)Te(3)](4-), which are composed of tetrahedral HgTe(4)
      and trigonal HgTe(3) units connected through the bridging Te(2-), (Te(2))(2-),
      and (Te(3))(2-) ligands. II is a layered compound containing InTe(4) tetrahedra
      that share corners and edges via Te, Te(2), and Te(3) units to form a 2D slab
      that contains relatively large voids. The [Zn(en)(3)](2+) template cations are
      filled in these voids and between the slabs. The primary building blocks of III
      are CuTe(4) tetrahedra that are linked by intralayer (Te(3))(2-) and interlayer
      (Te(2))(2-) units to form a 3D network with open channels that are occupied by
      the K(+) cations. All three compounds are rare polytelluride products of
      solvothermal reactions that contain both Te(2) and Te(3) fragments with unusual
      metal-tellurium coordination.

PMID- 11300840
TI  - Building unit and topological evolution in the hydrothermal DABCO-U-F system.
AB  - Compounds NDUF-1 ([C(6)H(14)N(2)](UO(2))(2)F(6); P2(1)/c, a = 6.9797(15) A, b =
      8.3767(15) A, c = 23.760(5) A, beta = 91.068(4) degrees, V = 1388.9(5) A(3), Z =
      4), NDUF-2 ([C(6)H(14)N(2)](2)(UO(2))(2)F(5)UF(7).H(2)O), NDUF-3
      ((NH(4))(7)U(6)F(31); R3, a = 15.4106(8) A, c = 10.8142(8) A, V = 2224.1(2) A(3),
      Z = 3), and NDUF-4 ([NH(4)]U(3)F(13)) have been synthesized hydrothermally from
      fixed composition reactant mixtures over variable time periods [DABCO
      (C(6)H(12)N(2)), UO(2)(NO(3))(2).6H(2)O, HF, and H(2)O; 2-14 days]. Observed is a
      systematic evolution of the structural building units within these materials from
      the UO(2)F(5) pentagonal bipyramid in NDUF-1 and -2 to the UF(8) trigonal prism
      in NDUF-2 and finally to the UF(9) polyhedron in NDUF-3 and -4 as a function of
      reaction time. Coupled to this coordination change is a reduction of U(VI) to
      U(IV) as well as a breakdown of the organic structure-directing agent from DABCO
      to NH(4)(+). These processes contribute to a structural transition from layered
      topologies (NDUF-1) to chain (NDUF-2), back to layered (NDUF-3), and ultimately
      to framework (NDUF-4) connectivities. The synthesis conditions, crystal
      structures, and possible transformation mechanisms within this system are
      presented.

PMID- 11300841
TI  - Formation of gallium dimers in the intermetallic compounds R(5)Ga(3) (R = Sc, Y,
      Ho, Er, Tm, Lu). Deformation of the Mn(5)Si(3)-type structure.
AB  - The R(5)Ga(3) (R = Sc, Y, Ho, Er, Tm, Lu) phases were prepared by high
      temperature solid-state techniques. The structure of monoclinic Sc(5)Ga(3) was
      determined by single-crystal X-ray diffraction means (C2/m, No. 12, Z = 4, a =
      8.0793(5) A, b = 14.003(1) A, c = 5.9297(3) A, beta = 90.994(5) degrees ), and
      those of the isotypic R(5)Ga(3), R = Y, Ho, Er, Tm, Lu, were determined by
      Guinier powder diffraction. The new Sc(5)Ga(3) structure is a deformation of the
      hexagonal Mn(5)Si(3) type (P6(3)/mcm) and contains two types of gallium dimers
      with d(Ga-Ga) = 2.91 and 3.14 A. The closely spaced Sc1 chains in the parent
      Mn(5)Si(3) type transform to zigzag chains in concert with displacements of the
      uniformly spaced gallium atoms to form dimers within distorted confacial square
      antiprisms of Sc. Matrix effects appear important in the different Ga(2) bond
      lengths. Electronic calculations reveal that the transformation from the
      hypothetical Mn(5)Si(3) to the Sc(5)Ga(3) type is aided by antibonding Ga-Ga
      interactions between the dimers that are pushed above E(F) and Ga-Ga and Ga-Sc
      bonding states just below E(F) that are stabilized. Sc(5)Ga(3) is appropriately
      metallic. Except for R = Sc, Lu, the arc-melted R(5)Ga(3) compounds above slowly
      transform on annealing at 1150 degrees C and below into tetragonal Ba(5)Si(3)
      type structures.

PMID- 11300842
TI  - Iron pentacarbonyl: are the axial or the equatorial iron-carbon bonds longer in
      the gaseous molecule?
AB  - The structure of iron pentacarbonyl, Fe(CO)(5), was reinvestigated by gas-phase
      electron diffraction using an experimental rotational constant available from the
      literature as a constraint on the structural parameters. The study utilized a
      B3LYP/6-311+G(d) ab initio quadratic force field, scaled to fit observed infrared
      wavenumbers, from which were calculated corrections for the effects of
      vibrational averaging on distances and certain other quantities useful for the
      structural analysis. The results confirm that the equatorial Fe-C bonds are
      longer than the axial ones, an important difference with the structure in the
      crystal where the equatorial Fe-C bonds are the shorter. Some distance (r(g)/A)
      and vibrational amplitude (l(alpha)/A) parameter values with estimated 2sigma
      uncertainties based on assumption of D(3h) symmetry are [r(Fe-C)] = 1.829(2),
      r(Fe-C)(eq) - r(Fe-C)(ax) = 0.032(20), [r(C=O)] = 1.146(2), r(C=O)(eq) -
      r(C=O)(ax) = 0.006(27), r(Fe-C)(ax) = 1.810(16), r(Fe-C)(eq) = 1.842(11),
      r(C=O)(ax) = 1.142(23), r(C=O)(eq) = 1.149(16), l(Fe-C)(ax) = l(Fe-C)(eq) =
      0.047(5), and l(C=O)(ax) = l(C=O)(eq) = 0.036(3).

PMID- 11300843
TI  - Crystal chemistry and physical properties of superconducting and semiconducting
      charge transfer salts of the type (BEDT-TTF)(4)[A(I)M(III)(C2O4)3]*PhCN (A(I) =
      H30,NH4,K; M(III) = Cr, Fe, Co, Al; BEDT-TTF =
      bis(ethylenedithio)tetrathiafulvalene.
AB  - Synthesis, structure determination by single-crystal X-ray diffraction, and
      physical properties are reported and compared for superconducting and
      semiconducting molecular charge-transfer salts with stoichiometry (BEDT
      TTF)(4)[A(I)M(III)(C(2)O(4))(3)].PhCN, where A(I) = H(3)O, NH(4), K; M(III) = Cr,
      Fe, Co, Al; BEDT-TTF = bis(ethylenedithio) tetrathiafulvalene. Attempts to
      substitute M(III) with Ti, Ru, Rh, or Gd are also described. New compounds with M
      = Co and Al are prepared and detailed structural comparisons are made across the
      whole series. Compounds with A = H(3)O(+) and M = Cr, Fe are monoclinic (space
      group C2/c), at 150, 120 K a = 10.240(1) A, 10.232(12) A; b = 19.965(1) A,
      20.04(3) A; c = 34.905(1) A, 34.97(2) A; beta = 93.69(1) degrees, 93.25(11)
      degrees, respectively, both with Z = 4. These salts are metallic at room
      temperature, becoming superconducting at 5.5(5) or 8.5(5) K, respectively. A
      polymorph with A = H(3)O(+) and M = Cr is orthorhombic (Pbcn) with a = 10.371(2)
      A, b = 19.518(3) A, c = 35.646(3) A, and Z = 4 at 150 K. When A = NH(4)(+), M =
      Fe, Co, Al, the compounds are also orthorhombic (Pbcn), with a = 10.370(5) A,
      10.340(1) A, 10.318(7) A; b = 19.588(12) A, 19.502(1) A, 19.460(4) A; c =
      35.790(8) A, 35.768(1) A, 35.808(8) A at 150 K, respectively, with Z = 4. All of
      the Pbcn phases are semiconducting with activation energies between 0.15 and 0.22
      eV. For those compounds which are thought to contain H(3)O(+), Raman spectroscopy
      or C=C and C-S bond lengths of the BEDT-TTF molecules confirm the presence of
      H(3)O(+) rather than H(2)O. In the monoclinic compounds the BEDT-TTF molecules
      adopt a beta' ' packing motif while in the orthorhombic phases (BEDT-TTF)(2)
      dimers are surrounded by monomers. Raman spectra and bond length analysis for the
      latter confirm that each molecule of the dimer has a charge of +1 while the
      remaining donors are neutral. All of the compounds contain approximately
      hexagonal honeycomb layers of [AM(C(2)O(4))(3)] and PhCN, with the solvent
      occupying a cavity bounded by [M(C(2)O(4))(3)](3-) and A. In the monoclinic
      series each layer contains one enantiomeric conformation of the chiral
      [M(C(2)O(4))(3)](3-) anions with alternate layers having opposite chirality,
      whereas in the orthorhombic series the enantiomers form chains within each layer.
      Analysis of the supramolecular organization at the interface between the cation
      and anion layers shows that this difference is responsible for the two different
      BEDT-TTF packing motifs, as a consequence of weak H-bonding interactions between
      the terminal ethylene groups in the donor and the [M(C(2)O(4))(3)](3-) oxygen
      atoms.

PMID- 11300844
TI  - Syntheses and characterization of the metal maleonitrilediselenolates [K([2.2.2]
      cryptand)]2[M(Se2C2(CN)2)2] (M = Ni, Pd, Pt) and
      [Ni(dmf)(5)Cl]2[Ni(Se2C2(CN)2)2].
AB  - Reaction of KNH(2), K(2)Se, Se, [2.2.2]-cryptand, and a metal source yields the
      metal bis(maleonitrilediselenolates) [K([2.2.2]
      cryptand)](2)[M(Se(2)C(2)(CN)(2))(2)] (M = Ni, 1; Pd, 2, Pt, 3). These compounds
      are isostructural and crystallize with four formula units in the monoclinic space
      group P2(1)/c in cells at T = 153 K with parameters (a (A), b (A), c (A), beta
      (deg), V (A(3))) of 12.220(1), 15.860(2), 15.306(1), 107.64(2), 2827(1) for 1;
      12.291(1), 15.669(1), 15.548(1), 108.55(1), 2839(1) for 2; and 12.292(3),
      15.671(3), 15.569(3), 108.59(3), 2842(1) for 3. The cation of 1 has been
      substituted to yield [Ni(dmf)(5)Cl](2)[Ni(Se(2)C(2)(CN)(2))(2)] (4).
      [Ni(dmf)(5)Cl](2)[Ni(Se(2)C(2)(CN)(2))(2)] (4) crystallizes with one molecule in
      the triclinic space group P1 in a cell with parameters (T = 153 K) of a =
      8.842(2) A, b =13.161(3) A, c = 13.831(3) A, alpha = 110.08(3) degrees, beta =
      95.23(3) degrees, gamma = 93.72(3) degrees, V = 1484(1) A(3). The electronic
      absorption and infrared spectra are characteristic of metal
      maleonitrilediselenolates. Cyclic voltammetry shows that the
      maleonitrilediselenolate (mns) complexes are more easily oxidized than their
      maleonitriledithiolate (mnt) analogues.

PMID- 11300845
TI  - Excited-state properties of Rh(2)(O(2)CCH(3))(4)(L)(2) (L = CH(3)OH, THF, PPh(3),
      py).
AB  - The photophysical properties of Rh(2)(O(2)CCH(3))(4)(L)(2) (L = CH(3)OH, THF =
      tetrahydrofuran, PPh(3) = triphenylphosphine, py = pyridine) were explored upon
      excitation with visible light. Time-resolved absorption shows that all the
      complexes possess a long-lived transient (3.5-5.0 micros) assigned as an
      electronic excited state of the molecules, and they exhibit an optical transition
      at approximately 760 nm whose position is independent of axial ligand. No
      emission from the Rh(2)(O(2)CCH(3))(4)(L)(2) (L = CH(3)OH, THF, PPh(3), py)
      systems was detected, but energy transfer from Rh(2)(O(2)CCH(3))(4)(PPh(3))(2) to
      the (3)pipi excited state of perylene is observed. Electron transfer from
      Rh(2)(O(2)CCH(3))(4)(PPh(3))(2) to 4,4'-dimethyl viologen (MV(2+)) and chloro-p
      benzoquinone (Cl-BQ) takes place with quenching rate constants (k(q)) of 8.0 x
      10(6) and 1.2 x 10(6) M(-1) s(-1) in methanol, respectively. A k(q) value of 2 x
      10(8) M(-1) s(-1) was measured for the quenching of the excited state of
      Rh(2)(O(2)CCH(3))(4)(PPh(3))(2) by O(2) in methanol. The observations are
      consistent with the production of an excited state with excited-state energy,
      E(00), between 1.34 and 1.77 eV.

PMID- 11300846
TI  - Anion-directed crystallization of coordination polymers: syntheses and
      characterization of Cu(4)(2-pzc)(4)(H(2)O)(8)(Mo(8)O(26)).2H(2)O and Cu(3)(2
      pzc)(4)(H(2)O)(2)(V(10)O(28)H(4)).6.5H(2)O (2-pzc = 2-pyrazinecarboxylate).
AB  - Two new copper 2-pyrazinecarboxylate (2-pzc) coordination polymers incorporating
      [Mo(8)O(26)](4-) and [V(10)O(28)H(4)](2-) anions were synthesized and
      structurally characterized: Cu(4)(2-pzc)(4))(H(2)O)(8)(Mo(8)O(26)).2H(2)O (1) and
      Cu(3)(2-pzc)(4)(H(2)O)(2)(V(10)O(28)H(4)).6.5H(2)O (2). Crystal data: 1,
      monoclinic, space group P2(1)/n, a = 11.1547(5) A, b = 13.4149(6) A, c =
      15.9633(7) A, beta = 90.816(1) degrees; 2, triclinic, space group P1, a =
      10.5896(10) A, b = 10.7921(10) A, c = 13.5168(13) A, alpha = 104.689(2) degrees,
      beta = 99.103(2) degrees, gamma = 113.419(2) degrees. Compound 1 contains [Cu(2
      pzc)(H(2)O)(2)] chains charge-balanced by [Mo(8)O(26)](4-) anions. In compound 2,
      layers of [Cu(3)(2-pzc)(4)(H(2)O)(2)] form cavities that are filled with
      [V(10)O(28)H(4)](2-) anions. The magnetic properties of both compounds are
      described.

PMID- 11300848
TI  - Synthesis and characterization of a tetranuclear cyclopentadienyl molybdenum
      compound with a mu(4)-sulfido ligand.

PMID- 11300847
TI  - Bimetallic reactivity. On the use of oxadiazoles as binucleating ligands.
AB  - Two (1,3,4)-oxadiazole ligands have been prepared. In one case the oxadiazole
      ring is flanked by two o-aniline groups, and in the other case it is an extension
      of the first where the amines are condensed with 2-picolyl groups. A monometallic
      copper(II) complex of the former has been prepared, and its crystal structure was
      determined. A number of bimetallic copper(II), cobalt(II), and nickel(II)
      complexes of the di-deprotonated latter ligand were prepared and isolated. The
      crystal structure of the cobalt(II) complex bearing two acetate bridges is
      reported. The work demonstrates that the seldom-employed oxadiazole ring can be
      used effectively for generating bimetallic complexes.

PMID- 11300849
TI  - Synthesis, characterization, and crystal structure of the water soluble copper(I)
      complex with trisulfonated triphenylphosphine.

PMID- 11300850
TI  - Syntheses and structures of LiAuS and Li(3)AuS(2).

PMID- 11300851
TI  - Insensitivity of the Nb-Nb distance in a paddle-wheel compound to bond
      multiplicity and axial ligation.

PMID- 11300852
TI  - Solution- and solid-phase strategies for the design, synthesis, and screening of
      libraries based on natural product templates: a comprehensive survey.

PMID- 11300854
TI  - Williamson ether synthesis on solid support: substitution versus elimination.

PMID- 11300853
TI  - Solid-phase synthesis of C-terminal peptide hydroxamic acids.

PMID- 11300855
TI  - Chemography: the art of navigating in chemical space.
AB  - Combinatorial chemistry needs focused molecular diversity applied to the druglike
      chemical space (drugspace). A drugspace map can be obtained by systematically
      applying the same conventions when examining the chemical space, in a manner
      similar to the Mercator convention in geography: Rules are equivalent to
      dimensions (e.g., longitude and latitude), while structures are equivalent to
      objects (e.g., cities and countries). Selected rules include size, lipophilicity,
      polarizability, charge, flexibility, rigidity, and hydrogen bond capacity. For
      these, extreme values were set, e.g., maximum molecular weight 1500, calculated
      negative logarithm of the octanol/water partition between -10 and 20, and up to
      30 nonterminal rotatable bonds. Only S, N, O, P, and halogens were considered as
      elements besides C and H. Selected objects include a set of "satellite"
      structures and a set of representative drugs ("core" structures). Satellites,
      intentionally placed outside drugspace, have extreme values in one or several of
      the desired properties, while containing druglike chemical fragments. ChemGPS
      (chemical global positioning system) is a tool that combines these predefined
      rules and objects to provide a global drugspace map. The ChemGPS drugspace map
      coordinates are t-scores extracted via principal component analysis (PCA) from 72
      descriptors that evaluate the above-mentioned rules on a total set of 423
      satellite and core structures. Global ChemGPS scores describe well the latent
      structures extracted with PCA for a set of 8599 monocarboxylates, a set of 45
      heteroaromatic compounds, and for 87 alpha-amino acids. ChemGPS positions novel
      structures in drugspace via PCA-score prediction, providing a unique mapping
      device for the druglike chemical space. ChemGPS scores are comparable across a
      large number of chemicals and do not change as new structures are predicted,
      making this tool a well-suited reference system for comparing multiple libraries
      and for keeping track of previously explored regions of the chemical space.

PMID- 11300856
TI  - Polymer-supported triazole and benzotriazole leaving groups. Three new examples
      and a comparison of their efficiency.
AB  - Three polymer-supported heterocyclic (triazole 4 and benzotriazoles 2, 8) leaving
      groups are described. The loading of 8 was clearly superior to those of 2 and 4.
      The efficiency of 8 was higher than those of previously reported benzotriazole
      resins 9a,b in the C-acylation of ketones.

PMID- 11300858
TI  - Synthesis of a new fluoro-Wang resin for solid-phase reaction monitoring by 19F
      NMR spectroscopy.
AB  - A new fluoro-Wang resin is presented which facilitates solid-phase reaction
      monitoring using 19F NMR. The resin is easily synthesized and amenable to scale
      up. The method described herein compliments single-bead FT-IR and 13C NMR
      techniques. This method allows monitoring of solid-phase reactions even if the
      resin bound intermediate is unstable to the cleavage conditions. In addition,
      this is a useful tool to study reaction kinetics on the solid phase.

PMID- 11300857
TI  - Preparation of a 990-member chemical compound library of hydantoin- and
      isoxazoline-containing heterocycles using multipin technology.
AB  - The development of a useful chemistry for the construction of polyfunctional
      heterocycles--first through solution and solid phase (resins) and then library
      production via SynPhase crowns--is reported. Bead-based synthetic work was done
      on Merrifield resin where treatment with benzylamine in the presence of DBU
      followed by reaction with 4-chloromethylbenzoyl chloride afforded amide-linked
      resin 9. Finally, TFA.NH2-polystyrene macro crowns were derivatized with 4
      (hydroxymethyl)benzoic acid to afford pin 14 which was coupled with Boc-protected
      amino acid 2 in the presence of DIC to deliver pin 15. Deprotection and reaction
      with phenyl isocyanate afforded urea functionalized pin 17 which underwent 1,3
      dipolar cycloaddition reaction to give pin 19. Finally, compound 20 was obtained
      with moderate diastereoselectivity (20:21::8:1) by the reaction of pin 19 with a
      catalytic amount of Et3N.

PMID- 11300859
TI  - A versatile and inexpensive apparatus for rapid parallel synthesis on solid
      support: description and synthesis illustration.
AB  - A new inexpensive and practical apparatus for solid-phase chemistry and parallel
      synthesis is described. This new apparatus fills an important void in the
      availability of portable tools for the synthesis of libraries of compounds in
      multi-milligram amounts. Individual reaction tube capacities range in size from 4
      mL to 500 mL of operating liquid volume. Reaction blocks of 36 tubes x 4 mL or 24
      tubes x 150 mL allow flexibility of operation. Insert tubes with frit ends
      function as filter sticks for resin wash and for maintenance of inert atmosphere.
      An electronic controller device connects to the reaction tubes for programmable
      entry of pulses of inert gas for resin mixing or vacuum for resin wash. The
      utility of this apparatus is illustrated by the synthesis of libraries based on 4
      methaneamine imidazoles.

PMID- 11300860
TI  - Tethered libraries: solid-phase synthesis of substituted urea-linked bicyclic
      guanidines.
AB  - The general concept of tethered combinatorial libraries of compounds in which two
      pharmacophores are found is described. In particular, an improved method for the
      solid-phase synthesis of bicyclic guanidines from reduced N-acylated dipeptides,
      and its use in the synthesis of urea-linked bicyclic guanidines, is described.
      The exhaustive reduction of glutamine-containing resin-bound N-acylated
      dipeptides, using borane-THF, generated compounds containing three secondary
      amines and one primary amine. Following selective trityl protection of the
      primary amine, treatment of the three secondary amines with
      thiocarbonyldiimidazole (CSIm2) and mercuric acetate (Hg(OAc)2) generated the
      resin-bound bicyclic guanidines. Following trityl deprotection, an Fmoc-amino
      acid was coupled. Upon removal of the Fmoc protecting group, the resulting
      primary amine was treated with hexyl isocyanate to generate the urea-linked
      bicyclic guanidines. The desired products were cleaved from the resin using
      hydrogen fluoride. The selection of building blocks and characterization of
      controls for the synthesis of a combinatorial library is discussed.

PMID- 11300861
TI  - Polymer-supported glyoxylate and alpha-imino acetates. Versatile reagents for the
      synthesis of alpha-hydroxycarboxylic acid and alpha-amino acid libraries.
AB  - Polymer-supported glyoxylate.monohydrate (3) and alpha-imino acetates (7) have
      been readily prepared from chloromethylated resin via two or three steps. The ene
      reactions of 3 with alkenes were successfully performed in the presence of
      Yb(OTf)3 (50 mol %) to afford, after cleavage from the polymer support, the
      corresponding alpha-hydroxycarboxylic acid esters in good yields. The reactions
      of 7 with silyl enolates, Danishefsky's diene, and alkenes also proceeded
      smoothly in the presence of Sc(OTf)3 (20 mol %) to give the corresponding alpha
      amino acid, pyridone, and tetrahydroquinoline derivatives, respectively, in good
      yields.

PMID- 11300862
TI  - Solid phase extraction purification of carboxylic acid products from 96-well
      format solution phase synthesis with DOWEX 1x8-400 formate anion exchange resin.
AB  - The anion exchange resin DOWEX 1x8-400 formate has been developed for the
      isolation or resin capture of carboxylic acids from solution phase reactions in a
      96-well format using a batchwise solid phase extraction technique. Eleven
      different anion exchange resins (formate forms) were evaluated for their
      efficiency at scavenging aryl and aliphatic carboxylic acids from solution. The
      model carboxylic acids had pK(a)s ranging from 3.40 to 4.89. Exchange efficiency
      onto the resin was pK(a) dependent with the carboxylic acids but not with their
      diisopropylethylammonium salts. Exchange off of the resin also showed pK(a)
      dependence with the stronger acids requiring more concentrated solvent acid for
      exchange. DOWEX 1x8-400 formate was determined to have superior capacity and the
      fastest exchange rate. Solvents suitable for exchanging the acids onto the resin
      were CH2Cl2, methanol, and various solvent/water mixtures. Solvents suitable for
      exchanging the carboxylic acids off of the resin were TFA/solvent or
      HCO2H/solvent mixtures. The resin was found to swell best in CH2Cl2 and in polar
      protic solvents such as water, alcohols, and acids. Application of this technique
      to the crude product mixtures from an arrayed reductive amination and an arrayed
      Stille reaction provided product carboxylic acids in yields averaging 57% and
      purities averaging 89%.

PMID- 11300863
TI  - Grafted macroporous polymer monolithic disks: a new format of scavengers for
      solution-phase combinatorial chemistry.
AB  - Polyethylene encased porous poly(chloromethylstyrene-co-divinylbenzene) disks
      have been prepared by polymerization in a cylindrical glass mold and cut to a
      disk format. Following attachment of a free radical azo initiator 4,4'-azobis(4
      cyanovaleric acid) to available functionalities at the surface of the pores, the
      polymerization of 2-vinyl-4,4-dimethylazlactone was initiated from the surface.
      To avoid an undesirable increase in flow resistance and to improve the yield of
      grafting, divinylbenzene was added to the polymerization mixture in order to form
      a layer of swellable reactive polymer gel within the pores. The use of these
      disks as scavenging filters to remove various amines from solutions in flow
      through operations was demonstrated by effective removal of amines in a very
      short period of time from their solutions in a variety of solvents, even
      including alcohols and water.

PMID- 11300864
TI  - A combinatorial approach to [1,5]benzothiazepine derivates as potential
      antibacterial agents.
AB  - [1,5]Benzothiazepines are widely used in a number of different therapeutic areas
      and therefore represent an interesting scaffold for de novo exploration. Recent
      literature reports suggest their value as antibacterial agents. The present paper
      reports the exploration of this scaffold for the generation of combinatorial
      libraries both in solution and on solid phase.

PMID- 11300865
TI  - Combinatorial liquid-phase synthesis of structurally diverse benzimidazole
      libraries.

PMID- 11300866
TI  - A novel series of highly potent benzimidazole-based microsomal triglyceride
      transfer protein inhibitors.
AB  - A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038
      were discovered. Incorporation of an unsubstituted benzimidazole moiety in place
      of a piperidine group afforded potent inhibitors of MTP in vitro which were
      weakly active in vivo. Appropriate substitution on the benzimidazole ring,
      especially with small alkyl groups, led to dramatic increases in potency, both in
      a cellular assay of apoB secretion and especially in animal models of cholesterol
      lowering. The most potent in this series, 3g (BMS-212122), was significantly more
      potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in
      both hamsters and cynomolgus monkeys.

PMID- 11300867
TI  - Investigation of the selectivity of oxymorphone- and naltrexone-derived ligands
      via site-directed mutagenesis of opioid receptors: exploring the "address"
      recognition locus.
AB  - The delta-selective opioid antagonist naltrindole (NTI), as well as the kappa
      selective opioid antagonists norbinaltorphimine (norBNI) and 5'
      guanidinonaltrindole (GNTI), are derived from naltrexone, a universal opioid
      antagonist. Previous studies have indicated that extracellular loop III is the
      key region for discrimination by naltrexone-derived selective ligands between the
      delta, mu, and kappa opioid receptor types. It has been proposed that selective
      ligands could bind to all three receptor types if the appropriate portions of the
      extracellular loops were eliminated. To investigate this possibility, several
      single-point mutant opioid receptors have been generated with the aim of
      conferring enhanced affinity of selective ligands for their nonpreferred receptor
      types. Mutations were made in all three types of opioid receptors with the focus
      on two positions at the extracellular end of transmembrane regions (TM) VI and
      VII. It was found that the delta-selective NTI could bind both mu and kappa
      receptors with significantly enhanced affinity when an aromatic residue in TM VII
      was replaced with alanine (mu[W318A] and kappa[Y312A]). Similarly, kappa
      selective antagonists, norBNI and GNTI, showed enhanced affinity for the
      mu[W318A] mutant and for both mu and delta receptors when a glutamate residue was
      incorporated into the extracellular end of TM VI (mu[K303E] and delta[W284E]).
      These results demonstrate that naltrexone-derived selective ligands achieve their
      selectivity via a combination of enhanced affinity of the address for a
      particular subsite along with loss of affinity due to steric interference at
      nonpreferred types. The results reveal key residues in the "address" recognition
      locus that contribute to the selectivity of opioid ligands and support the
      hypothesis that recognition of the naltrexone moiety is essentially the same for
      all three receptor types.

PMID- 11300868
TI  - Alpha(2) adrenoceptor agonists as potential analgesic agents. 3.
      Imidazolylmethylthiophenes.
AB  - A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands
      for the alpha(2) adrenoceptor. These compounds were tested in two animal models
      that are predictive of analgesic activity in humans. The 3-thienyl compounds were
      generally the most potent, particularly those with substitution in the 4
      position. A subset of the most active compounds was further evaluated for adverse
      cardiovascular effects in the anesthetized rat model. In addition to excellent
      binding at the alpha(2D) adrenoceptor, the 4-bromo analogues 20e and 21e were
      very active in the rat abdominal irritant test (RAIT) with ED(50) doses of 0.38
      and 0.31 mg/kg, respectively. We constructed a pharmacophore model based on the
      biological activity of the present series, dexmedetomidine (1), and
      conformationally restrained analogues 3 and 4.

PMID- 11300869
TI  - Inhibition of heme detoxification processes underlies the antimalarial activity
      of terpene isonitrile compounds from marine sponges.
AB  - A series of terpene isonitriles, isolated from marine sponges, have previously
      been shown to exhibit antimalarial activities. Molecular modeling studies
      employing 3D-QSAR with receptor modeling methodologies performed with these
      isonitriles showed that the modeled molecules could be used to generate a
      pharmacophore hypothesis consistent with the experimentally derived biological
      activities. It was also shown that one of the modeled compounds,
      diisocyanoadociane (4), as well as axisonitrile-3 (2), both of which have potent
      antimalarial activity, interacts with heme (FP) by forming a coordination complex
      with the FP iron. Furthermore, these compounds were shown to inhibit
      sequestration of FP into beta-hematin and to prevent both the peroxidative and
      glutathione-mediated destruction of FP under conditions designed to mimic the
      environment within the malaria parasite. By contrast, two of the modeled
      diterpene isonitriles, 7-isocyanoamphilecta-11(20),15-diene (12) and 7-isocyano
      15-isothiocyanatoamphilecta-11(20)-ene (13), that displayed little antimalarial
      activity also showed little inhibitory activity in these FP detoxification
      assays. These studies suggest that the active isonitrile compounds, like the
      quinoline antimalarials, exert their antiplasmodial activity by preventing FP
      detoxification. Molecular dynamics simulations performed with diisocyanoadociane
      (4) and axisonitrile-3 (2) allowed their different binding to FP to be
      distinguished.

PMID- 11300870
TI  - Pharmacophore analysis of the nuclear oxysterol receptor LXRalpha.
AB  - A cell-free assay was developed for the orphan nuclear receptor LXRalpha that
      measures the ligand-dependent recruitment of a peptide from the steroid receptor
      coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay
      (LiSA), the structural requirements for activation of the receptor by oxysterols
      and related compounds were studied. The minimal pharmacophore for receptor
      activation was shown to be a sterol with a hydrogen bond acceptor at C24.
      24(S),25-Epoxycholesterol (1), which meets this criterion, is among the most
      efficacious of the oxysterols and is an attractive candidate as the LXRalpha
      natural hormone. Cholenic acid dimethylamide (14) showed increased efficacy
      compared to 1, whereas the unnatural oxysterol 22(S)-hydroxycholesterol (4) was
      shown to be an antagonist of 1 in the LiSA. The structural requirements for SRC1
      recruitment in the LiSA correlated with the transcriptional activity of compounds
      in a cell-based reporter assay employing LXRalpha-GAL4 chimeric receptors. Site
      directed mutagenesis identified Trp(443) as an amino acid critical for activation
      of LXRalpha by oxysterol ligands. This information was combined with the
      structure-activity relationship developed from the LiSA to develop a 3D homology
      model of LXRalpha. This model may aid the design of synthetic drugs targeted at
      this transcriptional regulator of cholesterol homeostasis.

PMID- 11300871
TI  - Molecular modeling studies of the Akt PH domain and its interaction with
      phosphoinositides.
AB  - The serine-threonine protein kinase Akt is a direct downstream target of
      phosphatidylinositol 3-kinase (PI3-K). The PI3-K-generated phospholipids regulate
      Akt activity via directly binding to the Akt PH domain. The binding of PI3-K
      generated phospholipids is critical to the relocalization of Akt to the plasma
      membrane, which plays an important role in the process of Akt activation.
      Activation of the PI3-K/Akt signaling pathway promotes cell survival. To
      elucidate the structural basis of the interaction of PI3-K-generated
      phospholipids with the Akt PH domain with the objective of carrying out structure
      based drug design, we modeled the three-dimensional structure of the Akt PH
      domain. Comparative modeling-based methods were employed, and the modeled Akt
      structure was used in turn to construct structural models of Akt in complex with
      selected PI3-K-generated phospholipids using the computational docking approach.
      The model of the Akt PH domain consists of seven beta-strands forming two
      antiparallel beta-sheets capped by a C-terminal alpha-helix. The beta1-beta2,
      beta3-beta4, and beta6-beta7 loops form a positively charged pocket that can
      accommodate the PI3-K-generated phospholipids in a complementary fashion through
      specific hydrogen-bonding interactions. The residues Lys14, Arg25, Tyr38, Arg48,
      and Arg86 form the bottom of the binding pocket and specifically interact with
      the 3- and 4-phophate groups of the phospholipids, while residues Thr21 and Arg23
      are situated at the wall of the binding pocket and bind to the 1-phosphate group.
      The predicted binding mode is consistent with known site-directed mutagenesis
      data, which reveal that mutation of these crucial residues leads to the loss of
      Akt activity. Moreover, our model can be used to predict the binding affinity of
      PI3-K-generated phospholipids and rationalize the specificity of the Akt PH
      domain for PI(3,4)P2, as opposed to other phospholipids such as PI(3)P and
      PI(3,4,5)P3. Taken together, our modeling studies provide an improved
      understanding of the molecular interactions present between the Akt PH domain and
      the PI3-K-generated phospholipids, thereby providing a solid structural basis for
      the design of novel, high-affinity ligands useful in modulating the activity of
      Akt.

PMID- 11300872
TI  - Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi,
      Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential
      route to chemotherapy.
AB  - We have investigated the effects in vitro of a series of bisphosphonates on the
      proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania
      donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that
      nitrogen-containing bisphosphonates of the type used in bone resorption therapy
      have significant activity against parasites, with the aromatic species having in
      some cases nanomolar or low-micromolar IC(50) activity values against parasite
      replication (e.g. o-risedronate, IC(50) = 220 nM for T. brucei rhodesiense;
      risedronate, IC(50) = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing
      bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre
      squalene level, most likely by inhibiting farnesylpyrophosphate synthase.
      Bisphosphonates therefore appear to have potential in treating parasitic
      protozoan diseases.

PMID- 11300873
TI  - A potent, nonpeptidyl 1H-quinolone antagonist for the gonadotropin-releasing
      hormone receptor.
AB  - Extensive development of the structure-activity relationships of a screening lead
      determined three important pharmacophores for gonadotropin-releasing hormone
      (GnRH) receptor antagonist activity. Incorporation of the 3,4,5-trimethylphenyl
      group at the 3-position, 2-(2(S)-azetidinyl)ethoxy group at the 4-position, and N
      4-pyrimidinylcarboxamide at the 6-position of the quinolone core resulted in the
      identification of 4-(2-(azetidin-2(S)-yl)ethoxy)-7-chloro-2-oxo-3-(3,4,5
      trimethylphenyl)-1,2-dihydroquinoline-6-carboxylic acid pyrimidin-4-ylamide (1)
      as a potent antagonist of the GnRH receptor. A 10(4)-fold increase in in vitro
      binding affinity is observed for the GnRH receptor as compared to the initial
      screening lead. Compound 1 exhibits nanomolar binding activity and functional
      antagonism at the human receptor and is 7-fold less active at the rhesus
      receptor. Intravenous administration of compound 1 to rhesus monkeys results in a
      significant decrease of the serum levels of downstream hormones, luteinizing
      hormone (79% decrease in area under the curve) and testosterone (92% decrease in
      area under the curve), at a dose of 3 mg/kg. Quinolone 1 is a potent nonpeptidyl
      antagonist for the human GnRH receptor that is efficacious for the suppression of
      luteinizing hormone and testosterone in primates.

PMID- 11300874
TI  - High-throughput permeability pH profile and high-throughput alkane/water log P
      with artificial membranes.
AB  - This study reports on a novel, high-throughput assay, designed to predict
      passive, transcellular permeability in early drug discovery. The assay is carried
      out in 96-well microtiterplates and measures the ability of compounds to diffuse
      from a donor to an acceptor compartment which are separated by a 9-10 microm
      hexadecane liquid layer. A set of 32 well-characterized, chemically diverse drugs
      was used to validate the method. The permeability values derived from the flux
      factors between donor and acceptor compartments show a good correlation with
      gastrointestinal absorption in humans. For comparison, correlations based on
      experimental or calculated octanol/water distribution coefficients (log
      D(o/w,6.8)) were significantly lower. In addition, this simple and robust assay
      allows determination of pH permeability profiles, critical information to predict
      gastrointestinal absorption of ionizable drugs and difficult to obtain from cell
      culture experiments. Correction for the unstirred water layer effect allows to
      differentiate between effective and intrinsic membrane permeability and opens up
      the dynamic range of the method. In addition, alkane/water partition coefficients
      can be derived from intrinsic membrane permeabilities, making this assay the
      first high-throughput method able to measure alkane/water log P in the
      microtiterplate format.

PMID- 11300875
TI  - Synthesis of 2-amino-5-sulfanyl-1,3,4-thiadiazole derivatives and evaluation of
      their antidepressant and anxiolytic activity.
AB  - Recently a series of 2-amino-5-sulfanyl-1,3,4-thiadiazole derivatives bearing
      different substituents were synthesized and screened pharmacologically in order
      to evaluate their central nervous system activity. The purpose of this study was
      to evaluate the effects of the title compounds on CNS activity by varying the
      substituents in the thiadiazole moiety. It was found that some of these compounds
      possess marked antidepressant and anxiolytic properties comparable in efficiency
      to the reference drugs Imipramine and Diazepam. The most potent compound 3k was
      further investigated to complete its pharmacological profile with respect to
      undesired side effects. Behavioral results showed that 3k is a very promising
      compound, characterized by a mixed antidepressant-anxiolytic activity accompanied
      by a therapeutic dose range that is essentially 2 orders of magnitude less than
      that at which side effects such as sedation and amnesia are evident.

PMID- 11300876
TI  - Structure-activity relationship studies of 4-[2-(diphenylmethoxy)ethyl]-1
      benzylpiperidine derivatives and their N-analogues: evaluation of O-and N
      analogues and their binding to monoamine transporters.
AB  - In our effort to develop a pharmacotherapy for the treatment of cocaine
      addiction, we embarked on synthesizing novel molecules targeting the dopamine
      transporter (DAT) molecule in the brain as DAT has been implicated strongly in
      the reinforcing effect of cocaine. Our previously developed DAT-selective
      piperidine analogue, 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, was the
      basis for our current structure-activity relationship (SAR) studies exploring the
      significance of the contribution of the benzhydryl O- and N-atoms in these
      molecules in interacting with the DAT. Thus, we replaced the benzhydryl O-atom
      with an N-atom, altered the location of the benzhydryl N-atom to an adjacent
      position, and in one other occasion converted the benzhydryl O-ether linkage into
      an oxime-type derivative. Furthermore, we also evaluated the important
      contribution of the piperidine N-atom to binding by altering its pK(a) value
      chemically. Novel analogues were tested for potency in inhibiting [3H]WIN 35,428,
      [3H]citalopram, and [3H]nisoxetine binding at the DAT, serotonin transporter
      (SERT), and norepinepherine transporter (NET). [3H]DA was used to measure DA
      reuptake inhibition. The results indicated that the benzhydryl O- and N-atoms are
      exchangeable for the most part. On the other hand, an enhanced interaction with
      the SERT was observed when the benzhydryl N-atom moved to an adjacent position
      (21a; DAT (IC(50)) = 19.7, SERT (IC(50)) = 137 nM, NET (IC(50)) = 1111 nM). In
      either cases, further alkylation of the N-atom reduced the activity for the
      transporter. The presence of a powerful electron-withdrawing cyano group in
      compound 5d expectedly produced the most potent and selective ligand for the DAT
      (DAT (IC(50)) = 3.7 nM, DAT/SERT = 615). Selected compounds were further analyzed
      in the dopamine reuptake inhibition assay. Preliminary behavioral assessment of
      some of the selected compounds in mice indicated that these compounds are much
      less stimulating when compared with cocaine at comparable doses. In drug
      discrimination studies these selected compounds incompletely generalized from the
      cocaine stimulus in mice trained to discriminate 10 mg/kg cocaine from vehicle.

PMID- 11300877
TI  - New synthesis of benzo-delta-carbolines, cryptolepines, and their salts: in vitro
      cytotoxic, antiplasmodial, and antitrypanosomal activities of delta-carbolines,
      benzo-delta-carbolines, and cryptolepines.
AB  - The paper describes, in its first part, a new synthesis of benzo-delta
      carbolines, cryptolepines, and their salts. The strategy is based on the
      association between halogen-dance and hetero-ring cross-coupling. It is fully
      convergent and regioselective with interesting overall yields from 27% to 70%. A
      halogen-dance mechanism in quinoline series is also proposed. The formal
      synthesis of potential antimalarial compounds and the first total synthesis of 11
      isopropylcryptolepine are also described. In the second part, cytotoxic activity
      against mammalian cells and activities against Plasmodium falciparum and
      Trypanosoma cruzi of benzo-delta-carbolines and delta-carbolines were evaluated
      in vitro to study the structure-activity relationships. For benzo-delta
      carbolines, methylation at N-5 increases the cytotoxic and antiparasitic
      activities. A further alkylation on C-11 generally increases the cytotoxic
      activity but not the antiparasitic activity, cryptolepine and 11
      methylcryptolepine being the most active on both parasites. Taking advantage of
      the fluorescence of the indoloquinoline chromophore, cryptolepine was localized
      by fluorescence microscopy in parasite DNA-containing structures suggesting that
      these compounds act through interaction with parasite DNA as proposed for
      cryptolepine on melanoma cells. For delta-carbolines, methylation at N-1 is
      essential for the antimalarial activity. 1-Methyl-delta-carboline specifically
      accumulates in the intracellular parasite. It has weak cytotoxic activity and can
      be considered as a potential antimalarial compound.

PMID- 11300878
TI  - Comparative binding energy (COMBINE) analysis of influenza neuraminidase
      inhibitor complexes.
AB  - Neuraminidase is a surface glycoprotein of influenza viruses that cleaves
      terminal sialic acids from carbohydrates. It is critical for viral release from
      infected cells and facilitates viral spread in the respiratory tract. The
      catalytic active site of neuraminidase is highly conserved in all type A and B
      influenza viruses, making it an excellent target for antiinfluenza drug design.
      Indeed, neuraminidase inhibitors have recently become available in the clinic for
      the treatment of influenza. Here, we describe the use of 3D structures of
      neuraminidase-inhibitor complexes to derive quantitative structure-activity
      relationships (QSARs) to aid understanding of the mechanism of inhibition and the
      discovery of new inhibitors. Crystal structures of neuraminidase-inhibitor
      complexes were used alongside modeled complexes to derive QSAR models by
      COMparative BINding Energy (COMBINE) analysis (Ortiz, A. R.; Pisabarro, M. T.;
      Gago, F.; Wade, R. C. J. Med. Chem. 1995, 38, 2681-2691). The neuraminidase
      proteins studied include type A subtypes N2 and N9 (which have ca. 50% sequence
      identity) and an active site mutant of the N9 subtype. The inhibitors include
      sialic acid and benzoic acid analogues with diverse frameworks and substitution
      groups. By considering the contributions of the protein residues and a key water
      molecule to the electrostatic and van der Waals intermolecular interaction
      energies, a predictive and robust QSAR model for binding to type A neuraminidase
      was obtained. In this QSAR model, 12 protein residues and 1 bound water molecule
      are highlighted as particularly important for inhibitory activity. This QSAR
      model provides guidelines for structural modification of current inhibitors and
      the design of novel inhibitors in order to optimize inhibitory activity.

PMID- 11300879
TI  - Factors influencing agonist potency and selectivity for the opioid delta receptor
      are revealed in structure-activity relationship studies of the 4-[(N-substituted
      4-piperidinyl)arylamino]-N,N-diethylbenzamides.
AB  - A study of the effect of transposition of the internal nitrogen atom for the
      adjacent benzylic carbon atom in delta-selective agonists such as BW373U86 (1)
      and SNC-80 (2) has been undertaken. It was shown that high-affinity, fully
      efficacious, and delta opioid receptor-selective compounds can be obtained from
      this transposition. In addition to the N,N-diethylamido group needed as the delta
      address, the structural features identified to promote delta receptor affinity in
      the set of compounds studied included a cis relative stereochemistry between the
      3- and 4-substituents in the piperidine ring, a trans-crotyl or allyl substituent
      on the basic nitrogen, the lack of a 2-methyl group in the piperidine ring, and
      either no substitution or hydroxyl substitution in the aryl ring not substituted
      with the N,N-diethylamido group. Structural features found to be important for mu
      affinity include hydroxyl substitution in the aryl ring, the presence of a 2
      methyl group in a cis relative relationship to the 4-amino group as well as N
      substituents such as cyclopropylmethyl. It was also determined that mu receptor
      affinity could be increased while maintaining delta receptor affinity, especially
      when hydroxyl-substituted compounds are considered. Additionally, it was
      discovered that the somewhat lower mu/delta selectivities observed for the
      piperidine compounds relative to the piperazine-based ligands appear to arise as
      a consequence of the carbon-nitrogen transposition which imparts an overall lower
      delta and higher mu affinity to the piperidine-based ligands. This higher
      affinity for the mu receptor, apparently intrinsic to the piperidine-based
      compounds, suggests that ligands of this class will more easily be converted to
      mu/delta combination agonists compared to the piperazine ligands such as 1. This
      is particularly important since analogues of 1, which show both mu- and delta
      type activity, are now recognized as important for their strong analgesia and
      cross-canceling of many of the side effects found in agonists operating
      exclusively from either the delta or mu opioid receptor.

PMID- 11300880
TI  - Discovery of inhibitors of cell adhesion molecule expression in human endothelial
      cells. 1. Selective inhibition of ICAM-1 and E-selectin expression.
AB  - A critical early event in the inflammatory cascade is the induced expression of
      cell adhesion molecules on the lumenal surface of vascular endothelial cells.
      These adhesion molecules include E-selectin, ICAM-1, and VCAM-1, which serve to
      recruit circulating leukocytes to the site of the inflammation. These adhesive
      interactions allow the leukocytes to firmly adhere to and cross the vascular
      endothelium and migrate to the site of tissue injury. Pharmaceutical agents which
      would prevent the induced expression of one or more of the cell adhesion
      molecules on the endothelium might be expected to provide a novel mechanism to
      attenuate the inflammatory responses associated with chronic inflammatory
      diseases. A thieno[2,3-d]pyrimidine, A-155918, was identified from a whole-cell
      high-throughput assay for compounds which inhibited the tumor necrosis factor
      alpha (TNFalpha)-induced expression of E-selectin, ICAM-1, or VCAM-1 on human
      vascular endothelial cells. Traditional medicinal chemistry methods were applied
      to this low-micromolar inhibitor, resulting in the 2,4-disubstituted thieno[2,3
      c]pyridine A-205804, a potent and selective lead inhibitor of E-selectin and ICAM
      1 expression (IC(50) = 20 and 25 nM, respectively). The relative position of the
      nitrogen atom in the thienopyridine isomer was shown to be critical for activity,
      as was a small amide 2-substituent.

PMID- 11300881
TI  - Enantiospecific synthesis and pharmacological evaluation of a series of super
      potent, conformationally restricted 5-HT(2A/2C) receptor agonists.
AB  - The affinity of ligands for either the 5-HT(2A) or 5-HT(2C) agonist binding site
      was enhanced by modification of the 2,5-oxygen substituents that are found in
      typical hallucinogenic amphetamines such as 4b (DOB). Restriction of the
      conformationally flexible 2,5-dimethoxy substituents into fused dihydrofuran
      rings generally resulted in increased potency relative to the parent 2,5
      dimethoxy compounds. The pure enantiomers of these arylalkylamines were obtained
      by enantiospecific synthesis that involved acylation of the heterocyclic nucleus
      7 with N-trifluoroacetyl-protected D- or L-alanyl chloride, followed by ketone
      reduction and N-deprotection. The enantiomers demonstrated modest
      stereoselectivity at the two receptors. Several general trends within these
      classes of new compounds were observed during their pharmacological
      investigation. For most pairs of optical isomers tested, the R-enantiomers of the
      compounds containing heterocycle 7 bound with only slightly higher affinity than
      their S-antipodes at the 5-HT(2A) and 5-HT(2C) receptors. Likewise, functional
      studies indicated that the R-enantiomers generally displayed increased potency
      compared to the S-enantiomers. Aromatization of the dihydrofuran rings of these
      arylalkylamines further increased affinity and potency. Only a few compounds were
      full agonists with most of them possessing intrinsic activities in the range of
      60-80%. These compounds with a fully aromatic linear tricyclic nucleus are some
      of the highest-affinity ligands for the 5-HT(2A) receptor reported to date.

PMID- 11300882
TI  - Solid-phase synthesis and inhibitory effects of some pyrido[1,2-c]pyrimidine
      derivatives on leukocyte formations and experimental inflammation.
AB  - A number of pyrido[1,2-c]pyrimidines bearing a nitrogen, oxygen, or sulfur
      functionality at C-1 were synthesized on solid-phase using the iminophosphorane
      methodology and tested for their effects on leukocyte functions in vitro and
      antiinflammatory activity. Compound 5c was found to be a strong scavenger of
      superoxide anion and an inhibitor of chemiluminescence induced by 12-O
      tetradecanoylphorbol 13-acetate in human neutrophils. These pyrido[1,2
      c]pyrimidines inhibited the generation of PGE(2) by COX-2 in RAW 264.7
      macrophages stimulated with lipopolysaccharide. Compounds 7, 5f, 6, and 8
      inhibited enzyme activity, whereas the remaining compounds also acted on the
      induction phase. In addition, 5a-f, 6, and 7 administered p.o. at a dose of 20
      mg/kg showed antiinflammatory activity in the carrageenan mouse paw edema model,
      where they inhibited PGE(2) levels in inflamed paws without affecting the content
      of this eicosanoid in stomachs. Inhibition of PGE(2) production and superoxide
      scavenging may participate in the mechanism of the antiinflammatory action of
      these pyrido[1,2-c]pyrimidine derivatives.

PMID- 11300883
TI  - Temporary inactivation of plasma amine oxidase by alkylhydrazines. A combined
      enzyme/model study implicates cofactor reduction/reoxidation but cofactor
      deoxygenation and subsequent reoxygenation in the case of hydrazine itself.
AB  - It has been known for some time that hydrazine and its methyl and 1,1-dimethyl
      analogues induce inactivation of the copper-containing quinone-dependent plasma
      amine oxidase but that the activity recovers over time, suggesting metabolism of
      all three inhibitors. However, the mechanism responsible for loss and regain of
      activity has not been investigated. In this study a combination of enzyme studies
      under a controlled atmosphere along with model studies using 5-tert-butyl-2
      hydroxy-1,4-benzoquinone to mimic the 2,4,5-trihydroxyphenylalanine quinone (TPQ)
      cofactor of the enzyme suggest that regain of enzyme activity represents two
      different O(2)-dependent processes. In the case of methylhydrazine and 1,1
      dimethylhydrazine, we propose that the inactive methylhydrazone/azo form of the
      enzyme slowly rehydrates and eliminates MeN=NH to give the triol cofactor form,
      which instantly reoxidizes to the catalytically active quinone form in the
      presence of O(2). Metabolism of methylhydrazine represents its conversion to
      CH(4) and N(2), and of 1,1-dimethylhydrazine to CH(2)=O, CH(4), and N(2). In the
      case of hydrazine itself, however, we propose that the inactive hydrazone/azo
      form of the enzyme instead undergoes a slow decomposition, probably facilitated
      by the active-site copper, to give N(2) and a novel 5-desoxy resorcinol form of
      the cofactor. The latter undergoes a rapid, but noninstantaneous reoxygenation at
      C5 to restore the active cofactor form, also probably mediated by the active-site
      copper.

PMID- 11300884
TI  - Origins of stereoselectivity in intramolecular Diels-Alder cycloadditions of
      dienes and dienophiles linked by ester and amide tethers.
AB  - B3LYP/6-31+G(d) calculations of structures and relative energies for competing
      transition states for intramolecular Diels-Alder reactions of substituted 3,5
      hexadienyl acrylates and acrylamides show that boatlike conformations are
      sometimes favored in the forming ring that includes the tether.

PMID- 11300885
TI  - Mixed organofluorine-organosilicon chemistry. 13. One-pot synthesis of
      difluoroaldols from acylsilanes and trifluoromethyltrimethylsilane. application
      to the synthesis of a difluoro analogue of egomaketone.
AB  - Difluoroaldol compounds 3 were synthesized in a one-pot procedure involving an
      acylsilane 1, trifluoromethyltrimethylsilane (TFMTMS), and an aldehyde. The key
      intermediate of this reaction is a difluoroenoxysilane 2. Ytterbium triflate
      proved to be a very efficient catalyst for promoting the aldol type reaction
      under very mild conditions. The potential of this reaction for the convergent
      synthesis of difluorinated compounds was illustrated by the synthesis of
      difluoroegomaketone 7d through dehydration of the corresponding aldol compound
      3d.

PMID- 11300886
TI  - Microwave-mediated selective monotetrahydropyranylation of symmetrical diols
      catalyzed by iodine.
AB  - Selective protection of one hydroxyl group as its tetrahydropyranyl ether in 1,n
      symmetrical diol is achieved by iodine-catalyzed reaction of the diol with
      dihydropyranyl ether under microwave irradiation.

PMID- 11300887
TI  - Lifting of the degeneracy in semibullvalenes by remote and direct substituents: a
      quantitative study using variable-temperature carbon-13 NMR spectroscopy.
AB  - A series of six 1,5-(ethylmethyl)semibullvalenes (1a <==> 1a', 2 <==> 2', 3
      <==>3') and two 4(2)-substituted semibullvalenes (4 <==> 4'), each undergoing
      Cope equilibria between nondegenerate valence tautomers, was investigated by
      carbon-13 NMR spectroscopy at a range of temperatures in several different
      solvents. Gompper's treatment of substituent perturbation was extended,
      specifically accounting for the effects of the substituents on chemical shifts,
      to allow the determination of the thermodynamic parameters for these skewed
      equilibria. These new treatments were used to determine the population difference
      (f - f ') between the valence tautomers and the perturbation thermodynamic
      quantities DeltaH(P), DeltaS(P), and DeltaG(P). The slow-exchange limit was
      reached for the parent 1,5-(ethylmethyl)semibullvalenes 3a <==> 3a' from which it
      was established that the preferred valence tautomer is 3a with the ethyl group on
      the cyclopropane ring. Despite considerable effort, the slow-exchange limit could
      not be reached in any of our other remotely substituted semibullvalenes. Provided
      that the ethyl group always prefers the cyclopropyl position as in 3a, the 1
      ethyl-5-methylsemibullvalenes 1a, 2, and 3 are more stable by DeltaH(P) = 0.7-1.7
      kJ mol(-1) than their valence tautomers 1a', 2', and 3'. In the directly
      substituted semibullvalenes (4 left harpoon ovet right harpoon 4'), the preferred
      valence tautomers 4a and 4b have the bromine atom or the nitrile group on the
      vinyl position (C(4)) rather than on the cyclopropane ring (C(2)) and are more
      stable than 4a' and 4b' by DeltaH(P) = 4.8 and 7.0 kJ mol(-1), respectively.

PMID- 11300888
TI  - Regiospecific and stereoselective synthesis of functionalized and differently
      metalated alkenes by silyl- or stannylcupration of metalated acetylenes.
AB  - Differently metalated vinylcuprate intermediates resulting from silyl- or
      stannylcupration of silyl- and tin-containing acetylenes reacted with a range of
      electrophiles, including chlorosilanes and chlorostannanes, affording regio- and
      stereodefined differently metalated vic and gem silyl- and tin-trisubstituted
      alkenes. Some of these functionalized polymetalated olefins are interesting
      synthons in organic chemistry.

PMID- 11300889
TI  - Preparation of polycyclic systems by sequential 5-exo-digonal radical
      cyclization, 1,5-hydrogen transfer from silicon, and 5-endo-trigonal cyclization.
AB  - Radicals of type 1 undergo 5-exo diagonal cyclization, and the resulting vinyl
      radical abstracts hydrogen from silicon to afford a silicon-centered radical.
      This radical closes in a 5-endo trigonal manner to generate radicals of type 4,
      which are reduced (4 --> 5) by stannane, except when the starting acetylene
      carries a terminal trimethylstannyl group. In this case, radicals 4 expel
      trimethylstannyl radical to afford vinyl silanes 6. The stereochemical outcome of
      the radical cascade 1 --> 5 is controlled by the stereochemistry of the oxygen
      bearing carbon in 1 (see starred atom). The sequence can be initiated by carbon-,
      alpha-substituted carbon-, oxyacyl-, and carbamoyl radicals and generates a
      silicon-containing ring fused onto a carbocycle or heterocycle. Numerous examples
      are described, as well as a number of transformations of the final cyclization
      products, especially their response to n-Bu(4)NF and to BF(3).OEt(2), reagents
      that cleave the newly formed carbon-silicon bond.

PMID- 11300890
TI  - An improved and easy method for the preparation of 2,2-disubstituted 1
      nitroalkenes.
AB  - Reactions of ketones 1, nitromethane 2, and catalytic amount of piperidine 3 in
      the presence of mercaptan 6 generate beta-nitroalkyl sulfides 7-9. At 0 degrees C
      and by the use of dichloromethane as solvent, beta-nitroalkyl sulfides 7-9 can be
      oxidized by m-chloroperoxybenzoic acid (m-CPBA) 10 to generate beta-nitroalkyl
      sulfoxides 11-13 and undergo elimination in carbon tetrachloride solution to
      produce medium to high yield of 2,2-disubstituted 1-nitroalkenes 5. The
      irreversibility of the synthetic mechanism not only can overcome the
      reversibility of the Henry reaction in the synthesis of 2,2-disubstituted 1
      nitroalkenes 5 but also can generate the major products "exo-nitro olefins"5c-e
      when cyclic ketones 1c-e were used. Under similar conditions, medium to high
      yield of 5-substituted-2-nitromethyl-2-phenylthioadamantane 17 also can be
      prepared from the reaction of 5-substituted-2-adamantanones 15, nitromethane 2,
      piperidine 3, thiophenol 6a. The intermediate17 can be oxidized by m-CPBA 10 in
      dichloromethane solution and then undergo elimination at room temperature or can
      be dissolved in solvent, coated on silica gel, and then heated at 90-100 degrees
      C to generate 5-substituted-2-nitromethyleneadamantane 16.

PMID- 11300891
TI  - Condensation of laterally lithiated o-methyl and o-ethyl benzamides with imines
      mediated by (-)-sparteine. Enantioselective synthesis of tetrahydroisoquinolin-1
      ones.
AB  - The first asymmetric synthesis of tetrahydroisoquinolin-1-ones using a (-)
      sparteine-mediated lateral metalation-imine addition sequence to furnish 3-phenyl
      tetrahydroisoquinolinones 3a with enantioselectivities up to 81% ee is described
      (Scheme 4). For amide 7b, imine addition products 10 and 11 have been obtained
      with high diastereoselectivities (91-97% de) and enantioselectivities (91-98% ee)
      (Scheme 8).

PMID- 11300892
TI  - Aminoborohydrides. 12. Novel tandem S(N)Ar amination-reduction reactions of 2
      halobenzonitriles with lithium N,N-dialkylaminoborohydrides.
AB  - A novel tandem amination-reduction reaction has been developed in which 2-(N,N
      dialkylamino)benzylamines are generated from 2-halobenzonitriles and lithium N,N
      dialkylaminoborohydride (LAB) reagents. These reactions are believed to occur
      through a tandem S(N)Ar amination-reduction mechanism wherein the LAB reagent
      promotes halide displacement by the N,N-dialkylamino group, and the nitrile is
      subsequently reduced. This one-pot procedure is complimentary to existing
      synthetic methods and is an attractive synthetic tool for the nucleophilic
      aromatic substitution of halobenzenes with less nucleophilic amines. The (N,N
      dialkylamino)benzylamine products of this reaction are easily isolated after a
      simple aqueous workup procedure in very good to excellent yields.

PMID- 11300893
TI  - Theoretical study of nucleophilic substitution at two-coordinate sulfur.
AB  - A series of nucleophilic substitution reactions involving simple species
      (chloride, phosphide, methoxide, hydroxide, and amide) as nucleophile and leaving
      group in methylsulfenyl derivatives were examined at B3LYP/aug-cc-pVDZ. The
      reactions involving hydroxide and amide correspond to deprotonation and not
      substitution. The substitution reactions follow an addition-elimination pathway,
      possessing a triple-well potential energy surface. The intermediate along this
      pathway is of trigonal bipyramid geometry with the nucleophile and leaving group
      occupying apical positions.

PMID- 11300894
TI  - Furan ring oxidation strategy for the synthesis of macrosphelides A and B.
AB  - By using the convenient protocol for conversion of 2-substituted furans into 4
      oxo-2-alkenoic acids ((i) NBS, (ii) NaClO(2)), macrosphelide B (2) was
      synthesized from furyl alcohol 5 (>98% ee) and acid 6 (99% ee). The protocol was
      first applied to the PMB ether of 5 to afford acid 13b. On the other hand, DCC
      condensation of acid 6 with 5 gave 16 after deprotection of the TBS group.
      Condensation was again carried out between 13b and 16 to furnish the key ketone
      17, which upon reduction with Zn(BH(4))(2) afforded anti alcohol 18
      stereoselectively (15:1). After protection/deprotection steps, the furan 18 was
      converted to seco acid 3 by using the furan oxidation protocol mentioned above,
      and lactonization of 3 with Cl(3)C(6)H(2)COCl, Et(3)N, and DMAP afforded 22 (MOM
      ether of 2), which upon deprotection with TFA produced 2. Transformation of 22 to
      macrosphelide A (1) was then investigated. Although the chelation-controlled
      reduction of 22 should afford the desired anti alcohol 24, Zn(BH(4))(2) at <-90
      degrees C gave a 2 approximately 1:1 mixture of anti/syn alcohols. On the
      contrary, reduction with NaBH(4) in MeOH at -15 degrees C produced the syn isomer
      23 with >10:1 diastereoselectivity. Mitsunobu inversion of the resulting C(14)
      hydroxyl group and deprotection of the MOM group with TFA afforded 1. Similarly,
      reduction of 2 with NaBH(4) afforded the C(14)-epimer of 1 stereoselectively. The
      observed stereoselectivity in the reductions of 22 and 2 could be explained on
      the basis of computer-assisted calculation, which showed presence of the low
      energy conformers responsible for the stereoselective reduction. In addition,
      conversion of 2 to 1 was established, for the first time.

PMID- 11300895
TI  - alpha-thiocyanation of carbonyl and beta-dicarbonyl compounds using
      (dichloroiodo)benzene-lead(II) thiocyanate.
AB  - The combination reagent (dichloroiodo)benzene and lead(II) thiocyanate in
      dichloromethane effects oxidation of various enol silyl ethers, ketene silyl
      acetals, and beta-dicarbonyl compounds, thereby providing an efficient and
      convenient method for alpha-thiocyanation of carbonyl and beta-dicarbonyl
      compounds.

PMID- 11300896
TI  - Cyclization strategies for the synthesis of macrocyclic bisindolylmaleimides.
AB  - Three new approaches to the synthesis of macrocyclic bisindolylmaleimides 1-4
      have been identified. Two strategies afford 8, the penultimate intermediate for
      the synthesis of 1-4, in 73% and 32% yield by intramolecular cyclization of 31
      and 40, respectively. The optimum synthesis of 1 was achieved in nine steps and
      15% yield by intramolecular formation of the macrocycle and maleimide in one step
      by reaction of the sodium indolate of 12 with methyl indole-3-glyoxylate 47. The
      mechanism of this reaction has been elucidated, using the trityl-protected
      derivative, to involve initial formation of the tricarbonyl imide 48, followed by
      irreversible alkylation of the indole nitrogen to generate the 17-membered
      macrocycle 49. Cyclization of 49 to hydroxymaleimide 50 and subsequent
      dehydration afforded 8a. This approach eliminated the problem of dimerization
      observed in the intramolecular cyclization reactions.

PMID- 11300897
TI  - Influence of alkyl substitution on the gas-phase stability of 1-adamantyl cation
      and on the solvent effects in the solvolysis of 1-bromoadamantane.
AB  - 1-Adamantyl cations having three methyl groups or one, two, or three isopropyl
      groups on the 3-, 5-, and 7-positions were found by FT ICR to be more stable than
      the 1-adamantyl cation and that the stability increases with the number of
      isopropyl group. The relative stabilities calculated by PM3 were in good
      agreement with the experimental results. In contrast, the sequence of the rates
      for the solvolysis in nonaqueous solvents are 3,5,7-(Me)(3)-1-AdBr < 1
      bromoadamantane (1-AdBr) < 3,5,7-(n-Pr)(3)-1-AdBr < 3,5,7-(i-Pr)(3)-1-AdBr. The
      rates of solvolysis of 3,5,7-(i-Pr)(3)-1-AdBr and 3,5,7-(n-Pr)(3)-1-AdBr relative
      to 1-AdBr at 25 degrees C are 15 and 3.8 in EtOH, respectively, but markedly
      decreases with the increase in the amount of added water, reaching 0.84 and 0.15,
      respectively, in 60% EtOH. Reflecting these effects of water, the Grunwald
      Winstein (GW) relationship for 3,5,7-(i-Pr)(3)-1-AdBr and 3,5,7-(n-Pr)(3)-1-AdBr
      against Y(Br) is linear for nonaqueous alcohols (EtOH, MeOH, TFE-EtOH, TFE, 97%
      HFIP), but marked downward deviations are observed for aqueous organic solvents,
      in particular, aqueous ethanol and aqueous acetone. The effect of the alkyl
      substituents to diminish relative solvolytic reactivity in EtOH-H(2)O mixtures
      may be ascribed to a blend of steric hindrance to Betarphinsted base-type
      hydration to the beta-hydrogens and hydrophobic interaction of the alkyl groups
      with ethanol to make the primary solvation shell less ionizing. The introduction
      of one nonyl group to the 3-position showed much smaller deviations in the GW
      relationship than the case of 3,5,7-(n-Pr)(3)-1-AdBr. The markedly decelerated
      solvolysis of alkylated 1-bromoadamantanes in aqueous organic solvents is a
      kinetic version of anomalously diminished dissociation of alkylbenzoic acids in
      aqueous ethanol and aqueous tert-butyl alcohol that was demonstrated by Wepster
      and co-workers a decade ago and ascribed to hydrophobic effects.

PMID- 11300898
TI  - New, azide-free transformation of epoxides into 1,2-diamino compounds: synthesis
      of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu).
AB  - A new, azide-free transformation of the key precursor epoxide 6 to the influenza
      neuraminidase inhibitor prodrug oseltamivir phosphate (1, Tamiflu) is described.
      This sequence represents a new and efficient transformation of an epoxide into a
      1,2-diamino compound devoid of potentially toxic and hazardous azide reagents and
      intermediates and avoids reduction and hydrogenation conditions. Using catalytic
      MgBr(2).OEt(2) as a new, inexpensive Lewis acid, the introduction of the first
      amino function was accomplished by opening of the oxirane ring with allylamine
      followed by Pd/C-catalyzed deallylation to the amino alcohol 16. The introduction
      of the second amino group was then accomplished via an efficient reaction cascade
      involving a domino sequence preferably utilizing a transient imino protection.
      Selective acetylation of the resulting diamine 17 was achieved under acidic
      conditions providing the crystalline 4-acetamido-5-N-allylamino-derivative 18,
      which upon deallylation over Pd/C and phosphate salt formation afforded drug
      substance 1. The overall yield of this route from 6 of 35-38% exceeds the yield
      of the azide-based process (27-29%) and does not require any chromatographic
      purification.

PMID- 11300899
TI  - Synthesis of 2-substituted (+/-)-(2r,3r,5r)-tetrahydrofuran-3,5-dicarboxylic acid
      derivatives.
AB  - An efficient synthesis of 2-substituted (+/-)-(2R,3R,5R)-tetrahydrofuran-3,5
      dicarboxylic acid derivatives has been developed. Starting from 5-norborne-2-ol,
      the key intermediate (+/-)-methyl 5,6-exo,exo-(isopropylidenedioxy)-2
      oxabicyclo[2.2.1]heptane-3-exo-carboxylate (15) was synthesized in an efficient
      six-step sequence. The key transformation is the base-catalyzed methanolysis
      rearrangement of (+/-)-6,7-exo,exo-(isopropylidenedioxy)-4-exo-iodo-2
      oxabicyclo[3.2.1]octan-3-one (14). Further manipulation of the 3-substituent of
      (+/-)-methyl 5,6-exo,exo-(isopropylidenedioxy)-2-oxabicyclo[2.2.1]heptane-3-exo
      carboxylate (15) followed by deprotection of the diol moiety and ring opening
      catalyzed by RuCl(3)/NaIO(4) gave the title compounds in good yield.

PMID- 11300900
TI  - Solid-state photodimerization of cholest-4-en-3-one.
AB  - Crystalline cholest-4-en-3-one undergoes solid-state dimerization by UV radiation
      to give two ring A - ring A connected dimers. No dimerization occurs in solution.
      The first dimer, characterized by a cyclobutane ring, is formed by connection of
      C-2 and C-3 of a moiety with C-5' and C-6' of another moiety, respectively. The
      latter dimer has a six-membered ketal ring formed by connection of C-2 with C-5'
      and of O, linked to C-3, with C-3'. The structures have been determined by
      spectroscopic means. X-ray analysis of title compound evidences the proximity of
      the axial H-2 of a molecule to the C-4' of a molecule in the upper layer. The
      transfer of the hydrogen and the connection between C-2 and C-5' might be the
      driving force of dimerization.

PMID- 11300901
TI  - Synthesis of Fmoc-protected trans-4-methylproline.
AB  - Fmoc-protected trans-4-methylproline was synthesized starting from D-serine. The
      chiral scaffold of serine in the form of olefinated Garner's aldehyde 3 was used
      to control the diastereoselective formation of the new stereocenter on the
      hydrogenation of allylic alcohol 4. The diastereoselectivity (syn/anti ratio) of
      the process was 86:14, attained with Raney nickel. Hydrogen migration seems not
      to be the sole factor lowering the diastereoselectivity, as nickel is known not
      to promote double-bond migration. Instead, the moderate stereocontrol is
      attributed to the mobility of the side chain of 4, which allows the attack of
      hydrogen on both faces of the olefin (open transition state). A series of
      transformations led to ring precursor 8, which after recrystallization afforded
      the syn diastereoisomer in dr = 95:5. Protected trans-4-methylproline 11 was
      obtained from 8 in a straightforward fashion.

PMID- 11300902
TI  - A universal, photocleavable DNA base: nitropiperonyl 2'-deoxyriboside.
AB  - A universal, photochemically cleavable DNA base analogue would add desirable
      versatility to a number of methods in molecular biology. A novel C-nucleoside,
      nitropiperonyl deoxyriboside (NPdR, P), has been investigated for this purpose.
      NPdR can be converted to its 5'-DMTr-3'-CE-phosphoramidite and was incorporated
      into pentacosanucleotides by conventional synthesis techniques. The destabilizing
      effect on hybrid formation with a complementary strand when this P base opposes
      A, T, and G was found to be 3-5 kcal/mol, but 9 kcal/mol when it opposes C. Brief
      irradiation (lambda > 360 nm, 20 min) of DNA containing the P base and piperidine
      treatment causes strand cleavage giving the 3'- and 5'-phosphates. Two
      significant recent interests, universal/non-hydrogen-bonding base analogues and
      photochemical backbone cleavage, have thus been combined in a single molecule
      that serves as a light-based DNA scissors.

PMID- 11300903
TI  - Synthesis of novel cage oxaheterocycles.
AB  - m-CPBA-promoted Baeyer-Villiger oxidation of
      pentacyclo[6.3.0.0(2,6).0(3,10).0(5,9)]undecan-4-one (1) afforded the
      corresponding lactone 2 in 93% yield. Lithium aluminum hydride promoted reduction
      of lactones 2, 6, and 9, performed in the presence of BF(3).OEt(2) reagent,
      afforded the corresponding cage ethers, i.e., 4, 7, and 10, respectively. Two
      methods that can be used to replace a cage C=O group by ether oxygen without
      concomitant rearrangement are delineated. A key step in the first of these
      methods employs m-CPBA promoted "double Criegee rearrangement", which was used to
      convert pentacyclo[6.3.0.0(2,6).0(3,10).0(5,9)]undecan-4-one diethyl acetal (11)
      into 7,9-dioxapentacyclo-[8.3.0.0(2,6).0(3,12).0(5,11)]tridecan-8-one (12).
      Subsequently, 12 was converted into 4
      oxapentacyclo[6.3.0.0(2,6).0(3,10).0(5,9)]undecane (14) via a two-step reduction
      dehydration reaction sequence. The second method utilized PhI(OAc)(2)-I(2)
      reagent to convert cage lactols 15 and 17 into the corresponding cage ethers,
      i.e., 14 and 2-oxaadamantane (18), respectively.

PMID- 11300904
TI  - Synthesis of a fluorinated analogue of anticancer active ether lipids.
AB  - The synthesis of racemic 2'-(trimethylammonium)ethyl-3-hexadecyloxy-2-fluoro-2
      (methoxymethyl)prop-1-yl-phosphate (6), a fluorinated analogue of an anticancer
      active ether lipid 5 was realized with 3% overall yield in a nine-step synthesis
      starting from 2-methylene-1,3-propanediol (7) using a bromofluorination as the
      key step. Both enantiomers of the precursor 8 of the ether lipid 6 were
      synthesized by lipase-catalyzed desymmetrization of the diacetate 17, either by
      hydrolysis (83% ee) or by lipase-catalyzed acetylation of the diol 22 (82% ee).
      The antitumor activity of 6 has been found in an in vivo model of the
      methylcholanthrene-induced fibrosarcoma of mice.

PMID- 11300905
TI  - Evidence for intermolecular interaction between sulfonium and sulfide sulfur
      atoms and its application to synthesis of cyclic bis(disulfide) dimer.
AB  - On the basis of the remote Pummerer reaction of p-bis(alkylthio)-aromatic S
      oxides, the intermolecular interaction between the sulfonium and sulfide sulfur
      atoms is described. (1) In marked contrast to the Pummerer reaction of 1b-d(3)
      with (CF(3)CO)(2)O (J. Org. Chem. 1999, 64, 3190-3195), the reaction of 3,3',5,5'
      tetramesityl-4-(trideuteriomethylsulfinyl)-4'-(methylthio)biphenyl (1a-d(3)) as a
      sterically hindered analogue of 1b gave only 2a-d(2). (2) Both reactions of the
      two unsymmetrical regioisomers of 1-(ethylthio)-4-(methylthio)benzene S-oxide (5a
      and 5b) with (CF(3)CO)(2)O afforded a mixture of the mono-Pummerer products 6a
      and 6b, the bis-Pummerer product 7, and the bis-sulfide 8 in a similar ratio. The
      quenching at the initial stage of both reactions produced 5a, 5b, 8, and the bis
      sulfoxide 10 in a similar ratio. These results indicate the equilibrium in the
      intermolecular interaction between the sulfur atoms. (3) The reaction of the p
      bis(benzylthio)-aromatic S-oxide 16 with (CF(3)SO(2))(2)O gave the cyclic
      bis(disulfide) dimer 17 for the diphenyl sulfide and diphenylmethane spacers or
      the cyclic tetrakis(disulfide) tetramer 19 for the benzene and biphenyl spacers
      via the debenzylation of an intermolecular dithia dication. The cyclic bis(dithia
      dication) dimer A resulting from the intermolecular interaction between the
      sulfonium and sulfide sulfur atoms is proposed as an intermediate throughout the
      present reactions.

PMID- 11300906
TI  - A solvolytic C-C cleavage reaction of 6-acetoxycyclohexa-2,4-dienones:
      mechanistic implications for the intradiol catechol dioxygenases.
AB  - 6-Acetoxycyclohexa-2,4-dienones are found to undergo a rapid reaction in
      methanol/water under mildly basic conditions to give an acyclic ketoester as the
      major product for 6-phenyl and 6-methyl substrates. Reaction monitoring by UV
      spectroscopy indicates the formation of an unsaturated ketone reaction
      intermediate (lambda(max) 275 nm, R = Ph) and the transient appearance of a
      highly conjugated species. Reaction of the 6-phenyl substrate (4.95 x 10(-6) s(
      1)) is 2-fold faster than the 6-methyl substrate (2.47 x 10(-6) s(-1)). The
      reaction rate is first order with respect to substrate concentration, and the
      final step in the reaction is pH-dependent. No cleavage was observed for a
      substrate lacking an acetyl substituent. A reaction mechanism for C-C cleavage is
      proposed involving a benzene oxide-oxepin interconversion. The possible relevance
      to the catalytic mechanism of the intradiol catechol dioxygenases is discussed.

PMID- 11300907
TI  - 1-Trifluoromethyl epoxy ethers. Effect of hexafluoro-2-propanol on reactions with
      secondary aromatic amines: synthesis of 3-trifluoromethyl indole derivatives.
AB  - Trifluoromethyl epoxy ethers 1 and 2 reacted with aromatic amines in hexafluoro-2
      propanol at room temperature providing trifluoromethyl indolinols 3 and 4 in
      excellent isolated yields. 3-Trifluoromethyl indoles 9 and 10 could be prepared
      by treatment of indolinols with SOCl(2).

PMID- 11300908
TI  - Synthesis of functional aromatic multisulfonyl chlorides and their masked
      precursors.
AB  - The synthesis of functional aromatic bis(sulfonyl chlorides) containing an
      acetophenone and two sulfonyl chloride groups, i.e., 3,5-bis[4
      (chlorosulfonyl)phenyl]-1-acetophenone (16), 3,5-bis(chlorosulfonyl)-1
      acetophenone (17), and 3,5-bis(4-(chlorosulfonyl)phenyloxy)-1-acetophenone (18)
      via a sequence of reactions, involving in the last step the quantitative
      oxidative chlorination of S-(aryl)- N,N'-diethylthiocarbamate, alkyl- or benzyl
      thiophenyl groups as masked nonreactive precursors to sulfonyl chlorides is
      described. A related sequence of reactions was used for the synthesis of the
      aromatic trisulfonyl chloride 1,1,1-tris(4-chlorosulfonylphenyl)ethane (24). 4
      (Chlorosulfonyl)phenoxyacetic acid, 2,2-bis[[[4
      (chlorosulfonyl)phenoxyacetyl]oxy]methyl]-1,3-propanediyl ester (27), 5,11,17,23
      tetrakis(chlorosulfonyl)-25,26,27,28-tetrakis(ethoxycarbonylmethoxy)calix[4]arene
      (38), 5,11,17,23,29,35-hexakis(chlorosulfonyl)-37,38,39,40,41,42
      hexakis(ethoxycarbonylmethoxy)calix[6]arene (39), 5,11,17,23,29,35,41,47
      octakis(chlorosulfonyl)-49,50,51,52,53,54,55,56
      octakis(ethoxycarbonylmethoxy)calix[8]arene (40), 5,11,17,23-tetrakis(tert-butyl)
      25,26,27,28-tetrakis(chlorosulfonyl phenoxyacetoxy)calix[4]arene (44),
      5,11,17,23,29,35-hexakis(tert-butyl)-37,38,39,40,41,42
      hexakis(chlorosulfonylphenoxyacetoxy)calix[6]arene (45), and
      5,11,17,23,29,35,41,47-octakis(tert-butyl)-49,40,51,52,53,54,55,56
      octakis(chlorosulfonylphenoxyacetoxy)calix[8]arene (46) were synthesized by two
      different multistep reaction procedures, the last step of both methods consisting
      of the chlorosulfonation of compounds containing suitable activated aromatic
      positions. 2,4,6-Tris(chlorosulfonyl)aniline (47) was obtained by the
      chlorosulfonation of aniline. The conformation of two series of multisulfonyl
      chlorides i.e., 38, 39, 40 and 44, 45, 46, was investigated by (1)H NMR
      spectroscopy. The masked nonreactive precursor states of the functional aromatic
      multisulfonyl chlorides and the aromatic multisulfonyl chlorides reported here
      represent the main starting building blocks required in a new synthetic strategy
      elaborated for the preparation of dendritic and other complex organic molecules.

PMID- 11300909
TI  - Total syntheses of bengamides B and E.
AB  - Total syntheses of the cytotoxic marine natural products bengamides B and E are
      described. Both bengamides are prepared via amide coupling of a protected
      polyhydroxylated lactone intermediate 9 with a suitably substituted
      aminocaprolactam intermediate. Lactone 9 is prepared in five steps from
      commercially available alpha-D-glucoheptonic gamma-lactone. The key reactions are
      a selective deprotection of a 1,2-acetonide in the presence of a 1,3-acetonide
      and an (E)-selective olefination of an unstable aldehyde using a gem-dichromium
      reagent. The bengamide B lactam intermediate 10 is prepared in seven steps from
      commercially available (5R)-5-hydroxy-L-lysine (12). The desired S-configuration
      at the gamma-OH lactam position is established using the Mitsunobu reaction.

PMID- 11300910
TI  - Changes in the relative contribution of specific and general base catalysis in
      cationic micelles. The cyclization of substituted ethyl hydantoates.
AB  - The rate-surfactant profiles for the HO(-)- and AcO(-)-catalyzed ring closure of
      two ethyl hydantoates, E2 and E3, to hydantoins with three cetyltrimethylammonium
      salts (CTAX, X = Br(-), Cl(-), or AcO(-)) are measured in 0.02 and 0.2 M acetate
      buffers 50% base with starting pH 4.65. Marked accelerations associated with
      large pH increases are found in 0.02 M buffered CTAOAc. Smaller accelerations and
      smaller pH changes are observed in 0.2 M buffered CTAOAc and CTACl. From these
      profiles, the micellar rate constants for the specific base- and general base
      catalyzed reactions, and, respectively, of E2 and E3 are obtained separately. The
      resulting values of k(2,m)/k(w), E2/E3 rate constant ratios, and kinetic solvent
      isotope effects, KSIEs, are consistent with a strong predominance of the HO(-)
      reaction in the dilute buffer, while in the more concentrated buffer, specific
      and general catalysis compete for the two substrates. This result is in sharp
      contrast with that observed in water in which the reaction of E2 is almost
      exclusively specifically catalyzed. The increase in the general base-catalyzed
      pathway for E2 is attributed not to an increase in the rate constant for this
      pathway in micelles but to a smaller decrease than that for the specific
      catalysis (k(2,m)/k(w) = 0.2 and 0.4 for the specific and general catalysis,
      respectively). The different responses of the rate constants to the micellar
      media are interpreted as a larger effect of the interfacial polarity on the
      specific than on the general catalysis. The apparent contradiction between the
      rate constant decreases and the marked accelerations in micellar media is
      discussed in terms of pH changes, i.e., [HO(-)] changes, and of acetate inclusion
      via ion exchanges at micellar interfaces.

PMID- 11300911
TI  - Reactions of PhSCH(2)Li and NCCH(2)Li with benzaldehyde and benzophenone: when
      does the mechanism change from ET to polar?
AB  - The carbonyl-carbon kinetic isotope effect (KIE) and the substituent effect were
      measured for the reaction of phenylthiomethyllithium (PhSCH(2)Li, 1) with
      benzaldehyde and benzophenone, and cyanomethyllithium (NCCH(2)Li, 2) with
      benzaldehyde, and the results were compared with those for other lithium reagents
      such as MeLi, PhLi, CH(2)=CHCH(2)Li, and CH(2)=C(OLi)C(CH(3))(3). It was
      previously shown that the reactions of MeLi, PhLi, and CH(2)=CHCH(2)Li proceed
      via a rate-determining electron transfer (ET) process whereas the reaction of
      lithium pinacolone enolate goes through the polar (PL) mechanism. The reaction of
      1 with benzaldehyde gave no carbonyl-carbon KIE ((12)k/(13)k = 0.999 +/- 0.004),
      similar to that measured previously for the MeLi reaction with benzophenone
      ((12)k/(14)k = 1.000). The effect of substituents of the aromatic ring of
      benzaldehyde and benzophenone on the reactivity gave very small Hammett rho
      values of 0.17 +/- 0.03 and 0.26 +/- 0.05, respectively. These small rho values
      are again similar to that observed for the reaction of MeLi. Likewise the
      reactions of 2 with benzaldehydes gave small KIE and the rho value ((12)k/(13)k =
      0.996 +/- 0.004, rho = 0.14 +/- 0.02). Dehalogenation and enone-isomerization
      probe experiments for 2 showed no evidence for the presence of radical-ion pair
      of sufficient lifetime during the course of the reaction. It is concluded that
      the reactions of 1 and 2 with the aromatic carbonyl compounds proceed via the
      electron transfer-radical coupling mechanism with rate-determining ET as in the
      reactions of MeLi, PhLi, and CH(2)=CHCH(2)Li.

PMID- 11300912
TI  - Synthesis and properties of new thiourea-functionalized poly(propylene imine)
      dendrimers and their role as hosts for urea functionalized guests.
AB  - Five generations of poly(propylene imine) dendrimers have been modified by
      palmityl and adamantyl endgroups via a thiourea linkage. The synthesis of the
      thiourea dendrimers DAB-dendr-(NHCSNHAd)(n) and DAB-dendr-(NHCSNHC(16)H(33))(n)
      (n = 4, 8, 16, 32, 64) proceeds smoothly via the amino-terminated DAB dendrimer
      and the adamantyl and palmityl isothiocyanates, respectively. The properties of
      the thiourea dendrimers have been studied by IR and (1)H NMR, including
      relaxation (T1, T2) measurements. The thiourea dendrimers are used as multivalent
      hosts for a number of guest molecules containing a terminal urea-glycine unit in
      organic solvents. The host-guest interactions have been investigated using 1D-
      and NOESY-NMR. These investigations show that the guest molecules bind to the
      dendritic host via thiourea (host)-urea (guest) hydrogen bonding, and ionic
      bonding between the terminal guest carboxylate moiety and the outer shell
      tertiary amines of the dendrimer. The ability to bind guest molecules of the
      adamantyl- and palmitylthiourea dendrimers has been compared with their
      respective urea containing dendrimer analogues, by NMR-titration, and competition
      experiments. Upon complexation, the thiourea dendrimer hosts show a larger
      downfield NH shift than the corresponding urea dendrimer hosts, indicative of
      stronger hydrogen bonding in the complexed state. Furthermore, microcalorimetry
      has been used to determine binding constants for formation of the host-guest
      complexes; the binding constants are typically in the order of 10(4) M(-1). Both
      NMR and microcalorimetric studies show that the thiourea dendrimers bind the urea
      containing guests with somewhat higher affinity than the corresponding urea
      dendrimers.

PMID- 11300913
TI  - A very concise and stereoselective synthesis of 3-substituted cis-hex-3-ene-1,5
      diyne and corresponding epoxydiyne.

PMID- 11300914
TI  - Benzotriazole-mediated synthesis of 2,3-disubstituted allylic alcohols.

PMID- 11300915
TI  - Organic synthesis methodology. Preparation and diastereoselective birch reduction
      alkylation of 3-substituted 2-methyl-2,3-dihydroisoindol-1-ones.

PMID- 11300916
TI  - Inhibition of quinone-imine dye deamination by complexation with para-sulfonated
      calixarenes.

PMID- 11300917
TI  - Solid-phase synthesis of N-acyl-N'-alkyl/aryl disubstituted guanidines.

PMID- 11300918
TI  - Littoralisone, a novel neuritogenic iridolactone having an unprecedented
      heptacyclic skeleton including four- and nine-membered rings consisting of
      glucose from Verbena littoralis.

PMID- 11300919
TI  - Preparation of a resin-bound ruthenium phosphine complex and assessment of its
      use in transfer hydrogenation and hydrocarbon oxidation.

PMID- 11300921
TI  - Synthesis of 3-methoxycarbonylmethyl derivatives of dihydroquinolone and
      dihydrochromenone.

PMID- 11300920
TI  - Hydroxylated alpha,beta-unsaturated nitriles: stereoselective synthesis.

PMID- 11300922
TI  - Mitsunobu reaction using triphenylphosphine linked to non-cross-linked
      polystyrene.

PMID- 11300923
TI  - Reduction of N-acyl-2,3-dihydro-4-pyridones to N-acyl-4-piperidones using
      zinc/acetic acid.

PMID- 11300924
TI  - Imidoyl radicals as synthons of unstable acyl radicals.

PMID- 11300930
TI  - Reference laboratory telephone service quality.
AB  - OBJECTIVES: To establish the rates with which reference laboratories resolve
      inquiries telephoned to them from primary laboratories and to identify reference
      laboratory practices associated with higher rates of inquiry resolution. DESIGN
      AND PARTICIPANTS: For 2 months, or until 50 contacts had occurred, 545 primary
      laboratories participating in the College of American Pathologists Q-Probes
      laboratory quality improvement program prospectively documented and characterized
      telephone inquiries they made to a reference laboratory of their choice.
      Participants also cataloged their own laboratory's demographic and practice
      characteristics and their reference laboratory's customer service
      characteristics. MAIN OUTCOME MEASURE: Rates with which reference laboratories
      resolved telephone inquiries. RESULTS: Participants characterized 11 031 (78.7%)
      of 14 017 telephone inquiries as resolved by the reference laboratories. Ranked
      according to inquiry resolution rates, primary laboratories in the 90th
      percentile characterized reference laboratories as resolving 100% of their
      inquiries; those in the 10th percentile characterized reference laboratories as
      resolving only 54.2% of their inquiries. The rate of resolved inquiries was
      significantly higher (P =.0047) for participants using reference laboratories
      with 24-hour customer service than it was for participants using reference
      laboratories with less than 24-hour service. Most primary laboratories (80.9%)
      chose to monitor 1 of 11 national reference laboratories; in this subset, median
      rates of inquiry resolution ranged from 90.2% to 55.0% (P <.0001), despite no
      significant variation in other measured customer service characteristics.
      CONCLUSIONS: Primary laboratories experience significant differences in the rates
      with which reference laboratories resolve telephone inquiries. The performance
      benchmark for reference laboratories is resolution of at least 90% of telephone
      inquiries from primary laboratory customers.

PMID- 11300931
TI  - Aberrant localization of the neuronal class III beta-tubulin in astrocytomas.
AB  - BACKGROUND: The class III beta-tubulin isotype (betaIII) is widely regarded as a
      neuronal marker in development and neoplasia. In previous work, we have shown
      that the expression of betaIII in neuronal/neuroblastic tumors is differentiation
      dependent. In contrast, the aberrant localization of this isotype in certain
      nonneuronal neoplasms, such as epithelial neuroendocrine lung tumors, is
      associated with anaplastic potential. OBJECTIVE: To test the generality of this
      observation, we investigated the immunoreactivity profile of betaIII in
      astrocytomas. DESIGN: Sixty archival, surgically excised astrocytomas (8
      pilocytic astrocytomas, WHO grade 1; 18 diffuse fibrillary astrocytomas, WHO
      grade 2; 4 anaplastic astrocytomas, WHO grade 3; and 30 glioblastomas, WHO grade
      4), were studied by immunohistochemistry using anti-betaIII monoclonal (TuJ1) and
      polyclonal antibodies. A monoclonal antibody to Ki-67 nuclear antigen (NC-MM1)
      was used as a marker for cell proliferation. Antibodies to glial fibrillary
      acidic protein (GFAP) and BM89 synaptic vesicle antigen/synaptophysin were used
      as glial and neuronal markers, respectively. RESULTS: The betaIII
      immunoreactivity was significantly greater in high-grade astrocytomas (anaplastic
      astrocytomas and glioblastomas; median labeling index [MLI], 35%; interquartile
      range [IQR], 20%-47%) as compared with diffuse fibrillary astrocytomas (MLI, 4%;
      IQR, 0.2%-21%) (P <.0001) and was rarely detectable in pilocytic astrocytomas
      (MLI, 0%; IQR, 0%-0.5%) (P <.0001 vs high-grade astrocytomas; P <.01 vs diffuse
      fibrillary astrocytomas). A highly significant, grade-dependent relationship was
      observed between betaIII and Ki-67 labeling and malignancy, but this association
      was stronger for Ki-67 than for betaIII (betaIII, P <.006; Ki-67, P <.0001).
      There was co-localization of betaIII and GFAP in neoplastic astrocytes, but no
      BM89 synaptic vesicle antigen/synaptophysin staining was detected. CONCLUSIONS:
      In the context of astrocytic gliomas, betaIII immunoreactivity is associated with
      an ascending gradient of malignancy and thus may be a useful ancillary diagnostic
      marker. However, the significance of betaIII-positive phenotypes in diffuse
      fibrillary astrocytomas with respect to prognostic and predictive value requires
      further evaluation. Under certain neoplastic conditions, betaIII expression is
      not neuron specific, calling for a cautious interpretation of betaIII-positive
      phenotypes in brain tumors.

PMID- 11300932
TI  - Ebola virus glycoprotein demonstrates differential cellular localization in
      infected cell types of nonhuman primates and guinea pigs.
AB  - BACKGROUND: In vitro studies have previously shown that Ebola virus glycoprotein
      (GP) is rapidly processed and largely released from infected cells, whereas other
      viral proteins, such as VP40, accumulate within cells. OBJECTIVE: To determine
      infected cell types in which Ebola virus GP and VP40, individually, localize in
      vivo. METHODS: Immunohistochemistry and in situ hybridization using GP- and VP40
      specific antibodies and genetic probes were used to analyze archived tissues of
      experimentally infected nonhuman primates and guinea pigs and Vero E6 and 293
      cells infected in vitro. RESULTS: The GP antigen was consistently present in
      hepatocytes, adrenal cortical cells, fibroblasts, fibroblastic reticular cells,
      ovarian thecal cells, and several types of epithelial cells, but was not detected
      in macrophages and blood monocytes of animals, nor in Vero cells and 293 cells.
      All GP-positive and GP-negative cell types analyzed contained VP40 antigen and
      both GP and VP40 RNAs. CONCLUSIONS: Ebola virus GP appears to selectively
      accumulate in many cell types infected in vivo, but not in macrophages and
      monocytes. This finding suggests that many cell types may have a GP-processing
      pathway that differs from the pathway described by previous in vitro studies.
      Differential cellular localization of GP could be relevant to the pathogenesis of
      Ebola hemorrhagic fever.

PMID- 11300933
TI  - Approach to the diagnosis of thin basement membrane nephropathy in females with
      the use of antibodies to type IV collagen.
AB  - CONTEXT: Thin basement membrane nephropathy is recognized by a diffusely thin
      glomerular basement membrane (GBM) ultrastructurally. In contrast to Alport
      syndrome (AS), there is no GBM thickening, lamellation, or granular inclusions.
      Morphologically, there is overlap between thin basement membrane nephropathy and
      AS in female patients in whom there might be only thin GBM and no pathognomonic
      findings of AS. OBJECTIVE: To determine if the use of antibodies to collagen IV
      is helpful in making the distinction between thin basement membrane nephropathy
      and AS in female patients with primarily thin GBMs. DESIGN: We examined renal
      biopsies from 9 adult female patients with thin GBMs for the presence of alpha1,
      alpha3, alpha4, and alpha5 chains of type IV collagen by immunofluorescence.
      RESULTS: In 2 patients with segmental GBM staining, no suggestion for AS was
      found on physical examination or in their family history. In the remaining 7
      patients with normal GBM staining, 4 had family members with end-stage renal
      disease of unknown etiology, raising the suspicion of X-linked or autosomal
      recessive AS. Three patients were presumed to have thin basement membrane
      nephropathy. CONCLUSION: Segmental GBM staining for alpha3, alpha4, and alpha5
      chains of type IV collagen raises the suspicion of AS in the presence of adequate
      controls and other supporting evidence. Normal GBM staining for alpha3, alpha4,
      and alpha5 chains of type IV collagen, however, does not exclude AS.

PMID- 11300934
TI  - Ham56-immunoreactive macrophages in untreated infiltrating gliomas.
AB  - CONTEXT: Classic diagnostic neuropathologic teachings have cautioned against
      making the diagnosis of neoplasia in the presence of a macrophage population. The
      knowledge of macrophage distribution should prove useful when confronted with an
      infiltrating glioma containing macrophages. OBJECTIVE: To identify macrophages in
      untreated, infiltrating gliomas using the monoclonal antibody HAM56, and to
      confirm their presence in an untreated glioblastoma multiforme (GBM) with the
      serial analysis of gene expression (SAGE) method. METHODS: We evaluated the
      presence of macrophages in 16 cases of untreated, supratentorial infiltrating
      gliomas with the macrophage monoclonal antibody HAM56. We performed SAGE for one
      case of GBM and for normal brain tissue. RESULTS: In World Health Organization
      (WHO) grade II well-differentiated astrocytoma and oligodendroglioma, HAM56
      reactivity was noted only in endothelial cells, and unequivocal macrophages were
      not identified. In WHO grade III anaplastic astrocytoma and anaplastic
      oligodendroglioma, rare HAM56-positive macrophages were noted in solid areas of
      tumor. In WHO grade IV GBM, HAM56-positive macrophages were identified in areas
      of solid tumor (mean labeling index, 8.6%). In all cases of GBM, nonquantitated
      HAM56-positive macrophages were identified in foci of pseudopalisading cells
      abutting necrosis and in foci of microvascular proliferations. In none of the
      cases were granulomas or microglial nodules found, and there was no prior history
      of surgical intervention, radiation therapy, chemotherapy, or head trauma in
      these cases. By SAGE, the macrophage-related proteins osteopontin and macrophage
      capping protein were overexpressed 12-fold and eightfold, respectively, in one
      untreated GBM compared with normal brain tissue. In this case, numerous HAM56
      positive macrophages (labeling index, 24.5%) were present in the solid portion of
      tumor, and abundant nonquantified macrophages were identified in foci of
      pseudopalisading cells abutting necrosis and in foci of microvascular
      proliferations. CONCLUSIONS: This study confirms the utility of the monoclonal
      antibody HAM56 in identifying macrophages within untreated infiltrating gliomas.
      The overexpression of macrophage-related proteins in one case of GBM as detected
      by SAGE signifies that macrophages may be present in untreated GBMs.

PMID- 11300935
TI  - GEWF solution.
AB  - BACKGROUND: Lymph node status is an important prognostic factor in the staging of
      colorectal carcinoma. Several adjunctive solutions have been used to increase the
      yield of pericolic lymph nodes from colorectal cancer resection specimens.
      METHODS: During 1998 at the Grey Bruce Regional Health Centre (Owen Sound,
      Ontario), 67 colonic resections were performed for colorectal cancer. Lymph nodes
      were identified using GEWF solution (glacial acetic acid, ethanol, distilled
      water, and formaldehyde) in 35 cases, and by the conventional method of
      sectioning, inspection, and palpation in 32 cases. RESULTS: There were no
      significant differences between GEWF and non-GEWF cases with respect to patient
      age, length of resection, size of tumor, tumor histologic type, tumor
      differentiation, or depth of tumor penetration into the bowel wall. Use of GEWF
      led to a significant increase in the number of lymph nodes found (10.2 +/- 4.9
      per case) compared with non-GEWF cases (6.8 +/- 3.9 per case) (P =.002). In GEWF
      cases 358 lymph nodes were identified, 82 with metastases, whereas in the non
      GEWF cases 218 lymph nodes were found, 41 with metastases. The size of positive
      lymph nodes in the GEWF group (0.5 +/- 0.2 cm) was significantly smaller than in
      the non-GEWF group (0.7 +/- 0.4 cm) (P =.046). A greater percentage of positive
      lymph nodes in the GEWF cases (49/82, 60%) were 0.5 cm or smaller compared with
      the non-GEWF cases (17/41, 41%). CONCLUSIONS: GEWF increases the yield of lymph
      nodes recovered from colorectal cancer specimens and may lead to improved staging
      of this cancer; it is inexpensive and simple to use.

PMID- 11300936
TI  - Correlation of Ki-67 and p53 with the new World Health Organization/International
      Society of Urological Pathology Classification System for Urothelial Neoplasia.
AB  - OBJECTIVE: The present study examines p53 and Ki-67 staining patterns of the
      diagnostic entities included within the new World Health
      Organization/International Society of Urological Pathology (WHO/ISUP)
      classification of urothelial neoplasms. DESIGN: We retrospectively studied 151
      bladder biopsies from 81 patients with the following neoplasms: normal urothelium
      (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high
      grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4);
      papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12);
      low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n =
      31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67
      (MIB-1). Two hundred cells from each lesion were visually counted, and the
      percentage of positive cells was tabulated without knowledge of the WHO/ISUP
      diagnosis. RESULTS: In flat lesions, p53 positivity was of limited diagnostic
      utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and
      10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder,
      29% of the benign urothelial cells were p53 positive. In papillary lesions, p53
      positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3
      papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low
      grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling
      index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary
      carcinomas. In flat lesions, an increased Ki-67 LI separated out benign
      urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI,
      11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary
      hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI,
      2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma
      (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high
      grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary
      neoplasm of LMP. CONCLUSIONS: An increased proliferative index as demonstrated by
      immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary
      carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma
      but may be seen in benign-appearing urothelium, suggesting a "field effect" with
      occult molecular aberration.

PMID- 11300937
TI  - Morphometry and histology of gonads from 13 children with dysgenetic male
      pseudohermaphroditism.
AB  - BACKGROUND: Dysgenetic male pseudohermaphroditism (DMP) is a sexual
      differentiation disorder characterized by bilateral dysgenetic testes, persistent
      mullerian structures, and cryptorchidism in individuals with a 46,XY karyotype.
      However, the histologic criteria for the diagnosis of DMP are poorly established.
      OBJECTIVE: To determine gonadal histology in children with DMP. PATIENTS AND
      METHODS: Between 1996 and 1998, 13 patients with DMP were evaluated on our
      service. The clinical diagnosis of DMP was based on a 46,XY karyotype, sex
      ambiguity, high levels of follicle-stimulating hormone and low levels of
      antimullerian hormone, a decreased testosterone response to human chorionic
      gonadotropin stimulation without accumulation of testosterone precursors, and the
      presence of mullerian structures. Molecular sequencing the HMGbox region of the
      SRY gene did not reveal any mutations. Biopsies were performed for 22 of 26
      gonads (patient age at the time of biopsy, 16 months to 10 years). Conventional
      microscopy was used to evaluate mean tubular diameter, tubular fertility index,
      and number of Sertoli cells per tubular profile. RESULTS: All 26 gonads were
      located outside of the labioscrotal folds. Their histologic features varied from
      only a reduction in tubular size to features of a streak gonad. Five of the 22
      gonads grossly resembled a streak gonad. The mean tubular diameter was severely
      reduced (>30% reduction relative to the normal tubular diameter for the patient's
      age) in 4 gonads, markedly reduced (10%-30%) in 11 gonads, slightly reduced
      (<10%) in one gonad, and normal in one gonad. The tubular fertililty index,
      expressed as the percentage of tubular profiles containing germ cells, was
      severely reduced (<30% of normal values) in 9 gonads, markedly reduced (50%-30%)
      in 2 gonads, and normal in 6 gonads. The number of Sertoli cells per tubular
      profile was elevated in 16 gonads and normal in one gonad. Thin tubules
      surrounded by fibrous tissue were occasionally observed. CONCLUSION: The
      histologic findings confirmed the clinical diagnosis of DMP in every patient in
      the present series. However, gonadal histology was variable, and careful
      morphometric evaluation may be necessary to establish the diagnosis.

PMID- 11300938
TI  - Chronic myelomonocytic leukemia revealed by uncontrollable hematuria.
AB  - Nephrectomy was performed for uncontrollable unilateral hematuria in an
      apparently healthy 72-year-old man. The suburothelial connective tissue of the
      kidney was infiltrated by primitive myeloid cells with associated acute
      vasculitis and foci of extramedullary hematopoiesis. Subsequently, the patient
      was shown to have chronic myelomonocytic leukemia. Although renal involvement and
      vasculitis have been recorded previously in chronic myelomonocytic leukemia, this
      is the first occasion, to our knowledge, where their concurrence resulted in such
      a spectacular presentation.

PMID- 11300939
TI  - Nasal natural killer lymphoma associated with Epstein-Barr virus in a patient
      infected with human immunodeficiency virus.
AB  - Nasal natural killer (NK) lymphoma associated with Epstein-Barr virus (EBV) is a
      rare lymphoma that has not yet been reported in patients with human
      immunodeficiency virus (HIV). This report describes the first case, to our
      knowledge, of nasal NK cell lymphoma in an HIV-positive patient. A 50-year-old
      African man presented with an obstructive nasopharyngeal tumor, leading to the
      diagnosis of HIV infection. Nasal biopsy specimens showed NK cell lymphoma,
      confirmed on nasal tissues by morphologic, immunohistochemical, and polymerase
      chain reaction studies using a denaturing gradient gel electrophoresis technique
      that showed no T-cell receptor gamma rearrangement. The EBV was detected by in
      situ hybridization. The patient received chemotherapy but died from infection. To
      our knowledge, this is the first reported case of nasal NK cell lymphoma
      associated with EBV in an HIV patient. Involvement of EBV in HIV non-B-cell
      lymphomas may represent a further manifestation of opportunistic EBV infection
      arising in these patients.

PMID- 11300940
TI  - Blastomyces dermatitidis with large yeast forms.
AB  - Yeast forms of Blastomyces dermatitidis typically range from 8 to 20 microm in
      largest diameter. We report a rare case of primary pulmonary blastomycosis with
      an unusual morphology, in which we found significant numbers of large yeast forms
      ranging from 30 to 35 microm in diameter. To our knowledge, this is only the
      second reported case of giant forms of B dermatitidis. We also review the
      literature and discuss the possible association of this unusual morphology with
      immunosuppression in general and glucocorticoid use in particular.

PMID- 11300941
TI  - Malignant gastrointestinal stromal tumor showing remarkable whorl formations.
AB  - A case of malignant gastrointestinal stromal tumor (GIST) is reported.
      Histologically, spindle cell proliferation with remarkable whorl formations was
      predominant in the tumor. Immunohistochemically, the tumor cells were diffusely
      positive for CD117 (c-Kit) and vimentin and partially positive for CD34.
      Ultrastructurally, the desmosome-like structures and interdigitations occurred
      much more frequently in the areas with whorl formations. These organelles were
      considered to be closely associated with the whorl formations. Various kinds of
      cellular arrangements are revealed in GISTs, but remarkable whorl formations,
      such as in our case, are a rare variant pattern. Herein, we discuss the
      histopathologic differences between this and other tumors showing whorl
      formations and describe the meaning of this unique arrangement. GISTs are thought
      to be immature tumors, and, therefore, variations in histopathologic findings are
      recognized. Finally, the ultrastructural study of GISTs is useful for
      understanding the mechanisms forming whorl formations and the differentiation or
      pathogenesis of GISTs.

PMID- 11300942
TI  - Lymphoepithelioma-like carcinoma of the breast with associated sclerosing
      lymphocytic lobulitis.
AB  - The purpose of this article is to highlight an unusual form of breast carcinoma
      and discuss its differential diagnosis. A 50-year-old woman underwent wide local
      excision of a breast lump. Microscopic examination revealed features of a
      lymphoepithelioma-like carcinoma. Individual tumor cells were present within an
      abundant lymphoid stroma. Immunohistochemistry revealed the epithelial nature of
      the cells and excluded a diagnosis of lymphoma. In addition, surrounding
      nontumorous breast tissue displayed the histologic features of sclerosing
      lymphocytic lobulitis or lymphocytic mastopathy. This is the second report of a
      lymphoepithelioma-like carcinoma of the breast, but to the best of our knowledge,
      it is the first description of coexistent sclerosing lymphocytic lobulitis.

PMID- 11300943
TI  - Aneurysmal bone cyst of the larynx presenting with hypoglottic obstruction.
AB  - We report a new case of aneurysmal bone cyst of the larynx occurring in a 22-year
      old man. The lesion manifested with progressive breathing discomfort and appeared
      as a polypoid pedunculated mass attached to the subglottic mucosa.
      Microscopically, it featured numerous mononuclear and multinucleated giant cells
      surrounding cavernous spaces filled with blood. Foci of proliferating spindle
      cells and mature osteoid tissue could be recognized. There was no apparent
      relationship with the cricoid perichondrium. Clinical follow-up was negative for
      local recurrence. Based on this report and a review of the literature, we
      conclude that aneurysmal bone cyst of the larynx is phenotypically comparable to
      its bone homologue; however, its microscopic recognition may be difficult,
      especially on small biopsy fragments. Since it can be confused with several
      lesions, including telangiectatic osteosarcoma, awareness of this rare appearance
      of aneurysmal bone cyst is important to avoid unnecessary radical surgery.

PMID- 11300944
TI  - Extranodal lymphoplasmacytoid lymphoma (immunocytoma) presenting as small
      intestinal obstruction.
AB  - A 57-year-old woman presented with intermittent symptoms of intestinal
      obstruction. Workup provided nondiagnostic radiologic studies. An exploratory
      laparotomy revealed a segmental dilatation in the proximal ileum, which showed
      diffuse thickening of the intestinal wall. Microscopic examination of the
      affected area disclosed a diffuse transmural infiltrate composed of small
      lymphocytes, mature plasma cells, and lymphoplasmacytoid cells in different
      stages of maturation associated with extracellular periodic acid-Schiff-positive
      material. In addition, serum protein electrophoresis showed a monoclonal
      immunoglobulin M kappa paraprotein. Postoperative workup did not demonstrate
      evidence of systemic involvement. The morphologic features and
      immunohistochemical and molecular analyses were consistent with
      lymphoplasmacytoid lymphoma (immunocytoma). We report an unusual case of primary
      extranodal immunocytoma involving the small intestine and discuss its
      clinicopathologic features.

PMID- 11300945
TI  - Pigmented cardiac paraganglioma.
AB  - A pigmented left atrial paraganglioma was found at autopsy in a 40-year-old black
      man who died unexpectedly. The cause of death was ascribed to coronary artery
      disease. The atrial mass was sharply demarcated and polypoid, measured 4 cm in
      greatest dimension, and had a cut surface that revealed dark red-brown soft tumor
      tissue. Histopathologically, the neoplasm exhibited a classic organoid clustering
      of cells (zellballen) with a prominent capillary network. The chief cells
      contained a brown-black pigment with histochemical characteristics of melanin. We
      report a case of pigmented cardiac paraganglioma because of its rarity. To our
      knowledge, no mention has been made of the presence of pigment in previously
      reported cases of cardiac paragangliomas.

PMID- 11300946
TI  - Bilateral renal oncocytosis with renal failure.
AB  - Oncocytosis is a term recently used to describe diffuse renal involvement by
      numerous oncocytic nodules. We report herein a case of a 53-year-old man with end
      stage renal disease requiring hemodialysis. His kidneys were involved by numerous
      tumors. Histologic examination revealed more than 100 oncocytomas and an
      associated papillary renal cell carcinoma in the right kidney.

PMID- 11300947
TI  - True hemangiopericytoma of the nasal cavity.
AB  - Two cases of nasal tumors with pericytic myoid differentiation are reported. The
      tumors occurred in a 77-year-old woman and a 60-year-old man as polypoid lesions
      covered by normal mucosa. Histologically, the tumors were composed of uniform
      short spindle or stellate cells with indistinct cell borders arranged in narrow
      and short fascicles. Numerous blood vessels of various sizes were common in both
      cases. The tumor cells of both cases stained intensely with anti-vimentin and
      anti-actin antibodies, but not with anti-desmin, CD34, or anti-high-molecular
      weight caldesmon antibodies. Ultrastructural examination revealed well-developed
      actin thin filaments with dense bodies, subplasmalemmal plaques, intercellular
      junctions, and irregular discontinuous basement membranes. These histopathologic
      features suggest true pericytic differentiation of the tumors (true
      hemangiopericytoma), unlike soft tissue-type hemangiopericytoma. Generally,
      sinonasal hemangiopericytomas are subdivided into soft tissue-type
      hemangiopericytomas and true hemangiopericytomas identical to the cases presented
      here. Soft tissue-type hemangiopericytomas are frequently highly aggressive,
      whereas true hemangiopericytomas show localized benign behavior. Sinonasal true
      hemangiopericytomas should be strictly differentiated from soft tissue-type
      hemangiopericytomas.

PMID- 11300948
TI  - Retroperitoneal mucinous cystadenoma.
AB  - Primary retroperitoneal mucinous cystadenoma is an uncommon tumor found
      exclusively in women. Herein, we describe a patient who had resection of a large
      retroperitoneal cystic mass. Histologic, immunohistochemical, and electron
      microscopic examination of the lining epithelial cells showed features of
      mesothelial cells in addition to ovarian mucinous cystadenoma. These findings
      suggest that these tumors arise from inclusions of mesothelial cells and
      subsequent mucinous metaplasia of the lining cells to form a cystadenoma.
      Estrogen receptors may be implicated in tumor promotion, explaining the
      occurrence exclusively in women.

PMID- 11300949
TI  - Pathologic quiz case. A 49-year-old white man with a nodular mass in the liver.

PMID- 11300950
TI  - Pathologic quiz case. A human immunodeficiency virus-infected man with
      splenomegaly and radiologic evidence suggestive of rupture.

PMID- 11300951
TI  - Pathologic quiz case. Colon biopsy in a patient with diarrhea--Possible etiologic
      agent.

PMID- 11300952
TI  - Pathologic quiz case. Patient with duodenal strictures and a mass at the head of
      the pancreas.

PMID- 11300953
TI  - Pathologic quiz case. A pelvic mass with abdominal dissemination.

PMID- 11300954
TI  - Pathologic quiz case. Crystal deposition disease of the knee joint.

PMID- 11300955
TI  - Toxoplasmosis in a bone marrow transplant patient.

PMID- 11300956
TI  - The International Society of Addiction Journal Editors (ISAJE) has become
      established.

PMID- 11300957
TI  - Harm reduction: quo vadis?

PMID- 11300958
TI  - Injectable opiate maintenance in the UK: Is it good clinical practice?
AB  - This paper reviews the current practice of injectable opiate treatment (IOT) in
      the United Kingdom, i.e. the "British system" of prescribing injectable heroin
      and methadone, and considers some of the clinical and ethical issues it raises.
      There is very limited research evidence supporting either the safety or
      effectiveness of IOT as practised in Britain. In particular there is almost no
      evaluation of long-term outcomes of IOT, which is of potential concern given the
      possibility of some patients remaining indefinitely in IOT, the risk of vascular
      complications, and its higher cost compared with oral maintenance. It would be
      easy to assess this controversial intervention as in need of further research.
      However, striving towards best practice in IOT involves more than generating
      evidence. The likelihood of a patient receiving IOT in the United Kingdom appears
      to be influenced more by the personal inclinations of prescribers than by outcome
      data (if any), or identified community needs for access to IOT. The author asks
      is this good clinical practice and is it sustainable? The "British system" needs
      to modernise itself consistent with international paradigms of continuous quality
      improvement, and the NHS's own agenda of clinical governance.

PMID- 11300959
TI  - Injectable opiate maintenance in the United Kingdom--within a Medicines Act
      perspective.

PMID- 11300960
TI  - Methadone prescribing to opiate addicts by private doctors: comparison with NHS
      practice in south east England.
AB  - AIMS: To compare National Health Service (NHS) and private practice in
      prescribing methadone to opiate addicts. DESIGN AND PARTICIPANTS: Survey of
      community pharmacies during 1995 (one in four random sample) and during 1997 (one
      in two random sample) in which data were collected on all methadone prescriptions
      currently being dispensed to opiate addicts. SETTING: Dispensing community
      pharmacies in south east England. UNITS MEASURED: 829 methadone prescriptions
      (785 NHS and 44 private) from 1995, and 761 (703 NHS and 58 private) from 1997.
      MEASUREMENTS: (i) The prescribed daily dose of methadone; (ii) the form (oral
      mixture, tablets or ampoules); and (iii) the pick-up duration (daily collection
      of prescribed dose, through to weekly or fortnightly collection in a single pick
      up). FINDINGS: Private methadone prescriptions issued to addicts typically give
      twice the daily dose, are more than four times as likely to give the methadone in
      injectable form, and most commonly give prescriptions to be collected in a single
      large weekly or fortnightly installment instead of through daily dispensing,
      compared with NHS methadone prescriptions. CONCLUSIONS: The disparity between
      private and NHS methadone prescriptions is striking. The much higher doses, the
      lack of arrangements for installment collection and the frequent choice of
      injectable forms of methadone increase greatly the risk of abuse and diversion to
      the black market. Regulatory scrutiny of this private practice in the United
      Kingdom is currently minimal. Independent research is required to explore more
      fully the different nature of such private methadone prescribing.

PMID- 11300961
TI  - Street-level drug law enforcement and entry into methadone maintenance treatment.
AB  - AIMS: To test the hypothesis that drug law enforcement encourages entry into
      methadone maintenance treatment. DESIGN: Survey conducted as face-to-face
      interviews in methadone clinics, at needle exchange centres and on the street, in
      areas of widespread heroin dealing and use. SETTING: Sydney, Australia.
      PARTICIPANTS: Heroin users. MEASUREMENTS: Self-reported data on personal
      characteristics, and experience of drug law enforcement and methadone maintenance
      treatment. FINDINGS: Although keeping their relationship/family together emerged
      as the most important reason given by respondents for entering treatment,
      avoiding more trouble with police/courts was also rated by the majority of
      respondents as an important or very important reason for entering treatment. The
      results of logistic regression analysis show that, after controlling for other
      factors, heroin users who have had a friend or family member imprisoned are more
      likely to have tried methadone maintenance treatment. A heroin user's own
      experience of arrest and imprisonment was also found to increase the likelihood
      of having tried treatment but only when age and length of time as a regular user
      (which were related to the user's experience of arrest and imprisonment) were
      excluded from the set of control variables. Despite having extensive histories of
      contact with the police and criminal justice system, however, Asian, Middle
      Eastern and Aboriginal respondents showed less proclivity to enter treatment than
      Caucasian respondents. CONCLUSION: Drug law enforcement may have a role to play
      in heroin demand reduction but its effects are not evident for all ethnic groups
      and the separate effects of contact with police, age and time spent in the heroin
      market remain unclear.

PMID- 11300962
TI  - Prevalence of HIV and hepatitis B and self-reported injection risk behavior
      during detention among street-recruited injection drug users in Los Angeles
      County, 1994-1996.
AB  - AIMS: To describe injection risk behaviors while in detention in a sample of
      injection drug users (IDUs) in Los Angeles County. DESIGN AND SETTING: Cross
      sectional, interviewer-administered, face-to-face risk survey, and serological
      screening for HIV and hepatitis B conducted at four street locations in Los
      Angeles County between 1994 and 1996. All interviews were conducted in a non
      institutionalized setting. MEASUREMENTS: Ascertainment of self-reported risk
      behavior during detention and screening for HIV and hepatitis B surface antigen
      (HBsAg) and antibody to the core (HBcAb) seromarkers. PARTICIPANTS: Six hundred
      and forty-two participants were street-recruited during the study period. Seventy
      one per cent of the sample was male, the median age was 43 years, 61% were
      African-American, 27% were Latino, 8% were white and 36% considered themselves
      homeless. FINDINGS: Overall HIV prevalence was 3.0%; 3.1% tested positive for the
      hepatitis B surface antigen marker (HBsAg), and 80.3% for antibody to hepatitis B
      core antigen (HBcAb). After adjustment for length of injection drug use and
      recency of release from detention, HIV seroreactivity was significantly
      associated with history of detention due to possession of IDU paraphernalia (OR =
      1.9). The presence of the hepatitis B HBcAb seromarker was associated with
      injection drug use while in detention, (OR = 1.7), and having been ever arrested
      for possession of IDU paraphernalia (OR = 1.8). CONCLUSIONS: IDU detainees
      constitute a high risk group for blood-borne infections. Comprehensive prevention
      and health promotion efforts in the community need to include correctional
      facilities.

PMID- 11300963
TI  - Unsafe injecting practices among attendees of syringe exchange programmes in
      France.
AB  - AIMS: To describe syringe exchange programme attendees and their injection
      practices. DESIGN: Cross-sectional study (one week in 1998). Data were collected
      through a standardized questionnaire. SETTING: 60/74 syringe exchange programmes
      (SEPs) in France. PARTICIPANTS: Clients requesting syringes in 60 SEPs.
      MEASUREMENTS: Self-reports of drug use, injecting behaviour, sexual behaviour,
      serological status (HIV, HBV, HCV). Prevalence of unsafe injecting practices in
      the previous month such as: syringe sharing; and sharing other injection
      paraphernalia. FINDINGS: 1004 questionnaires were collected (response rate: 50%).
      The mean age of respondents was 30 years, and 70% were males. Among individuals
      tested, HIV reported prevalence was 19.2%, HCV 58.4% and HBV 20.8%. The mean
      duration of drug use was 11 years. Eighty-five percent were polydrug users and
      buprenorphine high-dosage was the substance most used (73%). In the previous
      month, 45% of the participants had re-used a syringe, 93% injected at least daily
      (mean 3.6 injections per day), 18% shared a syringe and 71% shared injection
      paraphernalia. In multivariate analyses, unsafe injecting practices were
      associated with heroin and cocaine use and with living in a couple. The cluster
      analysis identified five categories of IDUs: users of buprenorphine-HD (45% of
      the responders), morphine-sulphate (17%), benzodiazepines and other legal drugs
      (13%), methadone associated with other legal drugs (13%) and crack-cocaine (13%).
      The buprenorphine-HD group had better social status and safer injection
      practices. CONCLUSIONS: In France, despite an increase in the accessibility to
      syringes and substitution treatments, unsafe injecting practices persist among
      SEP attenders. Interventions should stress the importance of using sterile
      material for each injection, even with a steady sex partner.

PMID- 11300964
TI  - The association between substance use, unplanned sexual intercourse and other
      sexual behaviours among adolescent students.
AB  - AIMS: To determine the prevalence of high-risk sexual behaviours and the
      influence of substance use and unplanned sexual intercourse on multiple sexual
      partners, inconsistent condom use and reasons for not always using condoms among
      adolescent students. DESIGN: A standardized self-reported anonymous questionnaire
      administered to a representative sample of students. SETTING: The Canadian
      provinces of Nova Scotia, New Brunswick, Newfoundland and Labrador, and Prince
      Edward Island in 1998. PARTICIPANTS: 9997 students in grades 9, 10 and 12 in the
      public school system. MEASUREMENTS: Items on sexual intercourse, unplanned sexual
      intercourse, number of sexual partners, condom use, alcohol use, episodes of
      binge drinking and drunkenness, cigarette smoking and cannabis use. FINDINGS:
      About 37.5% of males and 39.7% of females reported having engaged in sexual
      intercourse in the 12 months prior to the survey. Of those, 68.0% of males and
      61.5% of females reported having engaged in unplanned sexual intercourse, 40.9%
      of males and 32.1% of females reported having more than one sexual partner, and
      49.9% of males and 64.1% of females reported inconsistent condom use. Unplanned
      sexual intercourse under the influence of alcohol or other drug was found to be
      an independent risk factor for multiple sexual partners and inconsistent condom
      use. CONCLUSION: The demonstration of an association between substance use,
      unplanned sexual intercourse and other sexual behaviours lends support to a harm
      minimization approach, including the provision of non-judgemental information and
      interventions addressing unplanned sexual intercourse under the influence of a
      substance.

PMID- 11300965
TI  - Closure of an open drug scene--a case register-based analysis of the impact on
      the demand for methadone maintenance treatment.
AB  - AIMS: To assess the impact of the closure of an open drug scene on the demand for
      methadone maintenance treatment (MMT). DESIGN: Interrupted time series analysis
      of case register-based data of all MMTs performed in the canton of Zurich
      (Switzerland) between June 16 1992 and July 7 1997. SETTING: Five private and 14
      state-controlled institutions as well as 330 general practitioners, 35
      psychiatrists, and 79 other specialists offering outpatient MMT. PARTICIPANTS:
      5210 opiate users with 9042 MMT episodes. MEASUREMENTS: Monthly number of entries
      into MMT before, during and after the closure of the Letten scene in February
      1995, MMT retention rates, participants' socio-demographic and drug-related data.
      FINDINGS: ARIMA modelling revealed 68 (95% CI = 31-105; p < 0.001) additional MMT
      admissions due to the dispersion of the open drug scene without a decrease in MMT
      retention rates. Socio-demographic and drug-related characteristics of patients
      entering MMT in the month of the closure did not significantly differ from other
      admissions. CONCLUSIONS: Law enforcement strategies to eliminate open drug scenes
      may increase the demand for MMT. Sufficient treatment facilities for opioid
      dependence should be provided when law enforcement activities against open drug
      scenes are planned.

PMID- 11300967
TI  - The prevalence of alcohol, cigarette and illicit drug use in a stratified sample
      of English adolescents.
AB  - OBJECTIVES: The aim of this study was to assess current levels of regular
      cigarette, alcohol and illicit drug use in adolescents in light of reported
      research by Goddard & Higgins (1999). DESIGN, SETTING, SUBJECTS: Survey of 9742
      pupils (aged 11-16) in a stratified sample of 28 schools in four Local Education
      Authority areas in Northern England, the Midlands and London. Data were collected
      during the latter part of 1999 and the first 3 months of 2000. MEASURES:
      Respondents were asked confidentially about their use, and extent of use, of
      psychotropic substances (cigarettes, alcohol and illicit drugs). RESULTS: The
      prevalence of reported daily cigarette use rose from 4.8% at age 11 to 24.1% at
      age 16. More girls than boys smoked (13.7%, 9.5%, chi(2) = 39.1, p < 0.0001).
      Reported monthly use of alcohol rose from 5.1% at age 11 to 36% at 16. Alcohol
      was drunk more by boys than girls (16.4% and 12.8% respectively, chi(2) = 23.0, p
      < 0.0001) Reported monthly illicit drug use rose from 0.9% at age 11 to 14.5% at
      age 16. No overall differences were found between boys and girls. CONCLUSIONS:
      The results confirm that rates of cigarette smoking, alcohol and illicit drug use
      rise rapidly in the early teenage years, with higher rates of smoking in girls
      and drinking in boys.

PMID- 11300966
TI  - Risk domains associated with an adolescent alcohol dependence diagnosis.
AB  - AIMS: To determine the contribution of familial, interpersonal, academic and
      early substance use factors to relative risk for an alcohol dependence (AD)
      diagnosis in adolescents. METHODS: Information on 619 adolescents and their 390
      sets of biological parents was obtained using the adolescent version of the Child
      Semi-Structured Assessment for the Genetics of Alcoholism (C-SSAGA) and the adult
      counterpart of this instrument, the Semi-Structured Assessment for the Genetics
      of Alcoholism (SSAGA). The C-SSAGA elicits a wide range of environmental, social,
      and psychiatric diagnostic information. Specific domain scale scores associated
      with an adolescent AD were computed, and generalized estimating equations (GEE)
      modeling was used to determine the odds ratio (relative risk) of the specified
      risk domains for an alcohol dependence diagnosis. FINDINGS: Risk factors for a
      DSM-III-R AD diagnosis included being at least 16 years of age, as well as
      negative parent-child interactions, school and personal-related difficulties
      (including the presence of an externalizing or internalizing DSM-III-R non
      alcohol-related diagnosis), and early experimentations with a variety of
      substances. CONCLUSIONS: An array of familial, interpersonal, academic and early
      substance use factors were strongly associated with adolescent AD. Given the
      findings of this study, further research to determine temporal relationships that
      might influence the onset of adolescent alcohol dependence is warranted.

PMID- 11300968
TI  - Public opinion on the health benefits of moderate drinking: results from a
      Canadian National Population Health Survey.
AB  - AIMS: To explore beliefs about the health benefits of drinking alcohol in the
      Canadian population. DESIGN: Secondary analysis of data from a national
      population health survey. PARTICIPANTS: Canadians age 12 or older (weighted n =
      72375) in all provinces but Alberta excluding those living in remote regions,
      native reserves and armed forces bases. MEASURES: Responses to questions
      concerning the definition of moderate drinking and the belief that moderate
      drinking can be good for health. Self-reports of age, gender, province of
      residence, quantity and frequency of drinking, health problems and indicators of
      alcohol dependence. FINDINGS: Fifty-seven per cent of respondents believed that
      moderate drinking has health benefits. Forty-seven per cent defined moderate
      drinking as drinking less than one drink a day and believed this to be good for
      health. Twelve per cent defined moderate drinking as one or more drinks a day and
      believed this is good for health. Belief in the health benefits of moderate
      drinking was more common among men, those age 45 or older, residents of Ontario
      and Quebec, more frequent drinkers and those with ischaemic heart disease. Those
      who believed in the health benefits of at least one drink a day were more often
      males, older persons and frequent, heavy drinkers. CONCLUSIONS: Belief in the
      health benefits of moderate drinking is generally associated with a conservative
      definition of moderate drinking. However, some drinkers at risk for alcohol
      problems may be influenced to drink by the belief that this can have health
      benefits or use this belief as an excuse for drinking.

PMID- 11300969
TI  - Drug liaison midwives.

PMID- 11300975
TI  - Does lipid lowering increase nonillness mortality?

PMID- 11300976
TI  - Is an extract of the fruit of agnus castus (chaste tree or chasteberry) effective
      for prevention of symptoms of premenstrual syndrome (PMS)?

PMID- 11300978
TI  - When are stool cultures indicated for hospitalized patients with diarrhea not
      caused by Clostridium difficile (C-diff)?

PMID- 11300977
TI  - Are angiotensin-converting enzyme (ACE) inhibitors effective in preventing
      migraine in nonhypertensive patients?

PMID- 11300979
TI  - Clinical inquiries. How can I improve patient adherence to prescribed medication?

PMID- 11300980
TI  - Clinical inquiries. What medications are safe and effective for heartburn during
      pregnancy?

PMID- 11300981
TI  - Validation of a single screening question for problem drinking.
AB  - OBJECTIVE: The researchers hoped to confirm the sensitivity and specificity of a
      single screening question for problem drinking: "When was the last time you had
      more than X drinks in 1 day?", where X=4 for women and X=5 for men. STUDY DESIGN:
      Cross-sectional study. POPULATION: Adult patients presenting to 3 emergency
      departments in Boone County, Missouri, for care within 48 hours of an injury.
      OUTCOMES MEASURED: The answers to the question were coded as never, more than 12
      months ago, 3 to 12 months ago, and within the past 3 months. Problematic
      drinking was defined as either hazardous drinking (identified by a 29-day
      retrospective interview) or a past-year alcohol use disorder (defined by
      questions from the Diagnostic Interview Schedule). RESULTS: There was a 70%
      participation rate. Of 2517 interviewed patients: 29% were hazardous drinkers;
      20% had a past-year alcohol use disorder; and 35% had either or both. Considering
      "within the last 3 months" as positive, the sensitivity of the single question
      was 86%, and the specificity was 86%. In men (n=1432), sensitivity and
      specificity were 88% and 81%; in women, 83% and 91%. Using the 4 answer options
      for the question, the area under the receiver-operating characteristic curve was
      0.90. Controlling for age, sex, tobacco use, injury severity, and breath alcohol
      level in logistic regression models changed the findings minimally. CONCLUSIONS:
      A single question about the last episode of heavy drinking has clinically useful
      sensitivity and specificity in detecting hazardous drinking and alcohol use
      disorders.

PMID- 11300982
TI  - Three questions can detect hazardous drinkers.
AB  - OBJECTIVE: The researchers evaluated the Alcohol Use Disorders Identification
      Test (AUDIT), the first 3 questions of the AUDIT (AUDIT-C), the third AUDIT
      question (AUDIT-3), and quantity-frequency questions for identifying hazardous
      drinkers in a large primary care sample. STUDY DESIGN: Cross-sectional survey.
      POPULATION: Patients waiting for care at 12 primary care sites in western
      Pennsylvania from October 1995 to December 1997. OUTCOMES MEASURED: Sensitivity,
      specificity, likelihood ratios, and predictive values for the AUDIT, AUDIT-C, and
      AUDIT-3. RESULTS: A total of 13,438 patients were surveyed. Compared with a
      quantity-frequency definition of hazardous drinking (> or =16 drinks/week for men
      and > or =12 drinks/week for women), the AUDIT, AUDIT-C, and AUDIT-3 had areas
      under the receiver-operating characteristic curves (AUROC) of 0.940, 0.949, and
      0.871, respectively. The AUROCs of the AUDIT and AUDIT-C were significantly
      different (P=.004). The AUROCs of the AUDIT-C (P<.001) and AUDIT (P <.001) were
      significantly larger than the AUDIT-3. When compared with a positive AUDIT score
      of 8 or higher, the AUDIT-C (score > or =3) and the AUDIT-3 (score > or =1) were
      94.9% and 99.6% sensitive and 68.8% and 51.1% specific in detecting individuals
      as hazardous drinkers. CONCLUSIONS: In a large primary care sample, a 3-question
      version of the AUDIT identified hazardous drinkers as well as the full AUDIT when
      such drinkers were defined by quantity-frequency criterion. This version of the
      AUDIT may be useful as an initial screen for assessing hazardous drinking
      behavior.

PMID- 11300983
TI  - In search of the Holy Grail for the detection of hazardous drinking.

PMID- 11300984
TI  - Physician behaviors that predict patient trust.
AB  - OBJECTIVE: The goal for this study was to assess the relative strength of the
      association between physician behaviors and patient trust. STUDY DESIGN AND
      POPULATION: Patients (N=414) enrolled from 20 community-based family practices
      rated 18 physician behaviors and completed the Trust in Physician Scale
      immediately after their visits. Trust was also measured at 1 and 6 months after
      the visit. The association between physician behaviors and trust was examined in
      regard to patient sex, age, and length of relationship with the physician.
      RESULTS: All behaviors were significantly associated with trust (P<.0001), with
      Pearson correlation coefficients (r) ranging from 0.46 to 0.64. Being comforting
      and caring, demonstrating competency, encouraging and answering questions, and
      explaining were associated with trust among all groups. However, referring to a
      specialist if needed was strongly associated with trust only among women
      (r=0.61), more established patients (r=0.62), and younger patients (r=0.63). The
      behaviors least important for trust were gentleness during the examination,
      discussing options/asking opinions, looking in the eye, and treating as an equal.
      CONCLUSIONS: Caring and comfort, technical competency, and communication are the
      physician behaviors most strongly associated with patient trust. Further research
      is needed to test the hypothesis that changes in identified physician behaviors
      can lead to changes in the level of patient trust.

PMID- 11300985
TI  - The benefits of a trusting physician-patient relationship.

PMID- 11300986
TI  - The association between perineal trauma and spontaneous perineal tears.
AB  - OBJECTIVE: We assessed whether women who had a perineal trauma (episiotomy or
      spontaneous tear of the second degree or higher) at the first delivery were at
      increased risk for spontaneous perineal tears at the next delivery, and whether
      the risk increases with the severity of previous perineal trauma. DESIGN:
      Retrospective cohort study. POPULATION: We included data from 1895 women who had
      their first and second deliveries at Saint-Sacrement Hospital, Quebec City,
      Canada, between 1985 and 1994. Our study was restricted to women who gave birth
      vaginally to a single living neonate at their first 2 deliveries and who did not
      have an episiotomy at the second delivery. We extracted the data from the
      Department of Obstetrics computerized database. OUTCOMES MEASURED: Spontaneous
      perineal tears (of second degree or higher) at the second delivery. RESULTS:
      Having a perineal trauma at the first delivery more than tripled the risk
      (relative risk=3.3; 95% confidence interval, 2.6-4.2) of spontaneous perineal
      tears at the second delivery. The risk of spontaneous perineal tears at the
      second delivery increased with the severity of previous perineal trauma at birth.
      CONCLUSIONS: Our results show that the risk of spontaneous perineal tears at
      subsequent deliveries increases with the presence and the severity of perineal
      trauma at the first delivery.

PMID- 11300987
TI  - Conducting the Direct Observation of Primary Care Study.
AB  - PURPOSE: This paper shares insights from the process of conducting the Direct
      Observation of Primary Care (DOPC) Study. That study involved a multimethod
      approach for evaluating the structure, process, and health system context of
      family practice. CONSENSUS PROCESS: The study participants (academic
      investigators, clinicians, and research nurses) met in groups. By reflecting on
      the study process, these groups identified insights that may be useful to other
      investigators planning or conducting primary care research. LESSONS: The story of
      the DOPC study is one of collaboration leading to innovation and the development
      of ongoing relationships and a persistent research trajectory. Six factors were
      identified as important to the success of the primary care research process: (1)
      A generalist perspective; (2) involvement of community practices and practicing
      clinicians as research partners; (3) commitment to a transdisciplinary team
      process; (4) a multimethod approach; (5) openness to emerging insights; and (6)
      thinking big, but starting small. CONCLUSIONS: A multimethod research process
      that involves collaboration between practicing clinicians, methodologists, and
      content experts can simultaneously test a priori hypotheses and discover
      important new insights about primary care practice.

PMID- 11300988
TI  - Management of the patient with otitis externa.

PMID- 11300989
TI  - Which patients with ulcer- or reflux-like dyspepsia will respond favorably to
      omeprazole?

PMID- 11300990
TI  - Does prophylactic mastectomy in women at high risk for breast cancer provide a
      psychological benefit?

PMID- 11300991
TI  - Are biannual Papanicolaou (Pap) tests useful in postmenopausal women? Does
      hormone replacement therapy (HRT) affect the development of cervical cytology
      abnormalities?

PMID- 11300992
TI  - Is low-dose dopamine effective in preventing renal dysfunction in patients in the
      intensive care unit (ICU)?

PMID- 11300993
TI  - Diabetes and foot ulcers.

PMID- 11300994
TI  - URI and antibiotics.

PMID- 11300995
TI  - URI and antibiotics.

PMID- 11300996
TI  - Silencing the siren: guidance cue hierarchies at the CNS midline.

PMID- 11300997
TI  - Virus evolution: how does an enveloped virus make a regular structure?

PMID- 11300998
TI  - Reinventing a common strategy for patterning the eye.

PMID- 11300999
TI  - Are complex behaviors specified by dedicated regulatory genes? Reasoning from
      Drosophila.

PMID- 11301000
TI  - Chimera analysis of the Clock mutation in mice shows that complex cellular
      integration determines circadian behavior.
AB  - The Clock mutation lengthens periodicity and reduces amplitude of circadian
      rhythms in mice. The effects of Clock are cell intrinsic and can be observed at
      the level of single neurons in the suprachiasmatic nucleus. To address how cells
      of contrasting genotype functionally interact in vivo to control circadian
      behavior, we have analyzed a series of Clock mutant mouse aggregation chimeras.
      Circadian behavior in Clock/Clock <--> wild-type chimeric individuals was
      determined by the proportion of mutant versus normal cells. Significantly, a
      number of intermediate phenotypes, including Clock/+ phenocopies and novel
      combinations of the parental behavioral characteristics, were seen in balanced
      chimeras. Multivariate statistical techniques were used to quantitatively analyze
      relationships among circadian period, amplitude, and suprachiasmatic nucleus
      composition. Together, our results demonstrate that complex integration of
      cellular phenotypes determines the generation and expression of coherent
      circadian rhythms at the organismal level.

PMID- 11301001
TI  - Pax6 is required for the multipotent state of retinal progenitor cells.
AB  - The molecular mechanisms mediating the retinogenic potential of multipotent
      retinal progenitor cells (RPCs) are poorly defined. Prior to initiating
      retinogenesis, RPCs express a limited set of transcription factors implicated in
      the evolutionary ancient genetic network that initiates eye development. We
      elucidated the function of one of these factors, Pax6, in the RPCs of the intact
      developing eye by conditional gene targeting. Upon Pax6 inactivation, the
      potential of RPCs becomes entirely restricted to only one of the cell fates
      normally available to RPCs, resulting in the exclusive generation of amacrine
      interneurons. Our findings demonstrate furthermore that Pax6 directly controls
      the transcriptional activation of retinogenic bHLH factors that bias subsets of
      RPCs toward the different retinal cell fates, thereby mediating the full
      retinogenic potential of RPCs.

PMID- 11301002
TI  - sidestep encodes a target-derived attractant essential for motor axon guidance in
      Drosophila.
AB  - At specific choice points in the periphery, subsets of motor axons defasciculate
      from other axons in the motor nerves and steer into their muscle target regions.
      Using a large-scale genetic screen in Drosophila, we identified the sidestep
      (side) gene as essential for motor axons to leave the motor nerves and enter
      their muscle targets. side encodes a target-derived transmembrane protein (Side)
      that is a novel member of the immunoglobulin superfamily (IgSF). Side is
      expressed on embryonic muscles during the period when motor axons leave their
      nerves and extend onto these muscles. In side mutant embryos, motor axons fail to
      extend onto muscles and instead continue to extend along their motor nerves.
      Ectopic expression of Side results in extensive and prolonged motor axon contact
      with inappropriate tissues expressing Side.

PMID- 11301003
TI  - Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively
      inhibits G protein-coupled chemoattraction.
AB  - Transmembrane B ephrins and their Eph receptors signal bidirectionally. However,
      neither the cell biological effects nor signal transduction mechanisms of the
      reverse signal are well understood. We describe a cytoplasmic protein, PDZ-RGS3,
      which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric
      G protein signaling (RGS) domain. PDZ-RGS3 can mediate signaling from the ephrin
      B cytoplasmic tail. SDF-1, a chemokine with a G protein-coupled receptor, or
      BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action
      being selectively inhibited by soluble EphB receptor. This study reveals a
      pathway that links reverse signaling to cellular guidance, uncovers a novel mode
      of control for G proteins, and demonstrates a mechanism for selective regulation
      of responsiveness to neuronal guidance cues.

PMID- 11301004
TI  - Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell
      polarity signaling to the actin cytoskeleton.
AB  - Frizzled (Fz) and Dishevelled (Dsh) are components of an evolutionarily conserved
      signaling pathway that regulates planar cell polarity. How this signaling pathway
      directs asymmetric cytoskeletal reorganization and polarized cell morphology
      remains unknown. Here, we show that Drosophila Rho-associated kinase (Drok) works
      downstream of Fz/Dsh to mediate a branch of the planar polarity pathway involved
      in ommatidial rotation in the eye and in restricting actin bundle formation to a
      single site in developing wing cells. The primary output of Drok signaling is
      regulating the phosphorylation of nonmuscle myosin regulatory light chain, and
      hence the activity of myosin II. Drosophila myosin VIIA, the homolog of the human
      Usher Syndrome 1B gene, also functions in conjunction with this newly defined
      portion of the Fz/Dsh signaling pathway to regulate the actin cytoskeleton.

PMID- 11301005
TI  - The GGAs promote ARF-dependent recruitment of clathrin to the TGN.
AB  - The GGAs constitute a family of modular adaptor-related proteins that bind ADP
      ribosylation factors (ARFs) and localize to the trans-Golgi network (TGN) via
      their GAT domains. Here, we show that binding of the GAT domain stabilizes
      membrane-bound ARF1.GTP due to interference with the action of GTPase-activating
      proteins. We also show that the hinge and ear domains of the GGAs interact with
      clathrin in vitro, and that the GGAs promote recruitment of clathrin to liposomes
      in vitro and to TGN membranes in vivo. These observations suggest that the GGAs
      could function to link clathrin to membrane-bound ARF.GTP.

PMID- 11301006
TI  - Structural basis of the redox switch in the OxyR transcription factor.
AB  - The Escherichia coli OxyR transcription factor senses H2O2 and is activated
      through the formation of an intramolecular disulfide bond. Here we present the
      crystal structures of the regulatory domain of OxyR in its reduced and oxidized
      forms, determined at 2.7 A and 2.3 A resolutions, respectively. In the reduced
      form, the two redox-active cysteines are separated by approximately 17 A.
      Disulfide bond formation in the oxidized form results in a significant structural
      change in the regulatory domain. The structural remodeling, which leads to
      different oligomeric associations, accounts for the redox-dependent switch in
      OxyR and provides a novel example of protein regulation by "fold editing" through
      a reversible disulfide bond formation within a folded domain.

PMID- 11301007
TI  - Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their
      inactivation by C-terminal tyrosine phosphorylation.
AB  - The effect of C-terminal tyrosine phosphorylation on molecular motions in the Src
      kinases Hck and c-Src is investigated by molecular dynamics simulations. The SH2
      and SH3 domains of the inactive kinases are seen to be tightly coupled by the
      connector between them, impeding activation. Dephosphorylation of the tail
      reduces the coupling between the SH2 and SH3 domains in the simulations, as does
      replacement of connector residues with glycine. A mutational analysis of c-Src
      expressed in Schizosaccharomyces pombe demonstrates that replacement of residues
      in the SH2-SH3 connector with glycine activates c-Src. The SH2-SH3 connector
      appears to be an inducible "snap lock" that clamps the SH2 and SH3 domains upon
      tail phosphorylation, but which allows flexibility when the tail is released.

PMID- 11301009
TI  - The Fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly
      primed for fusogenic activation at endosomal pH.
AB  - Semliki Forest virus (SFV) has been extensively studied as a model for analyzing
      entry of enveloped viruses into target cells. Here we describe the trace of the
      polypeptide chain of the SFV fusion glycoprotein, E1, derived from an electron
      density map at 3.5 A resolution and describe its interactions at the surface of
      the virus. E1 is unexpectedly similar to the flavivirus envelope protein, with
      three structural domains disposed in the same primary sequence arrangement. These
      results introduce a new class of membrane fusion proteins which display lateral
      interactions to induce the necessary curvature and direct budding of closed
      particles. The resulting surface protein lattice is primed to cause membrane
      fusion when exposed to the acidic environment of the endosome.

PMID- 11301008
TI  - Locations of carbohydrate sites on alphavirus glycoproteins show that E1 forms an
      icosahedral scaffold.
AB  - There are 80 spikes on the surface of Sindbis virus arranged as an icosahedral
      surface lattice. Each spike consists of three copies of each of the glycoproteins
      E1 and E2. There are two glycosylation sites on E1 and two on E2. These four
      sites have been located by removal of the glycosylation recognition motifs using
      site-specific mutagenesis, followed by cryoelectron microscopy. The positions of
      these sites have demonstrated that E2 forms the protruding spikes and that E1
      must be long and narrow, lying flat on the viral surface, forming an icosahedral
      scaffold analogous to the arrangement of the E glycoprotein in flaviviruses. This
      arrangement of E1 leads to both dimeric and trimeric intermolecular contacts,
      consistent with the observed structural changes that occur on fusion with host
      cell membranes, suggesting a similar fusion mechanism for alpha- and
      flaviviruses.

PMID- 11301010
TI  - BACH1, a novel helicase-like protein, interacts directly with BRCA1 and
      contributes to its DNA repair function.
AB  - BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH
      helicase family. BACH1 binds directly to the BRCT repeats of BRCA1. A BACH1
      derivative, bearing a mutation in a residue that was essential for catalytic
      function in other helicases, interfered with normal double-strand break repair in
      a manner that was dependent on its BRCA1 binding function. Thus, BACH1/BRCA1
      complex formation contributes to a key BRCA1 activity. In addition, germline
      BACH1 mutations affecting the helicase domain were detected in two early-onset
      breast cancer patients and not in 200 matched controls. Thus, it is conceivable
      that, like BRCA1, BACH1 is a target of germline cancer-inducing mutations.

PMID- 11301011
TI  - Structure that opens the gate and opens the door.

PMID- 11301012
TI  - Shifting receptive fields.

PMID- 11301013
TI  - Drosophila gustation: a question of taste.

PMID- 11301014
TI  - The circadian clocks of mice and men.

PMID- 11301015
TI  - A turn of the helix: preventing the glial fate.

PMID- 11301016
TI  - A convoluted way to die.

PMID- 11301017
TI  - The grass roots of synapse suppression.

PMID- 11301018
TI  - The LDL receptor gene family: (un)expected signal transducers in the brain.

PMID- 11301019
TI  - Single-cell electroporation for gene transfer in vivo.
AB  - We report an electroporation technique for targeting gene transfer to individual
      cells in intact tissue. Electrical stimulation through a micropipette filled with
      DNA or other macromolecules electroporates a single cell at the tip of the
      micropipette. Electroporation of a plasmid encoding enhanced green fluorescent
      protein (GFP) into the brain of intact Xenopus tadpoles or rat hippocampal slices
      resulted in GFP expression in single neurons and glia. In vivo imaging showed
      morphologies, dendritic arbor dynamics, and growth rates characteristic of
      healthy cells. Coelectroporation of two plasmids resulted in expression of both
      proteins, while electroporation of fluorescent dextrans allowed direct
      visualization of transfer of molecules into cells. This technique will allow
      unprecedented spatial and temporal control over gene delivery and protein
      expression.

PMID- 11301020
TI  - Structure of the RCK domain from the E. coli K+ channel and demonstration of its
      presence in the human BK channel.
AB  - The intracellular C-terminal domain structure of a six-transmembrane K+ channel
      from Escherichia coli has been solved by X-ray crystallography at 2.4 A
      resolution. The structure is representative of a broad class of domains/proteins
      that regulate the conductance of K+ (here referred to as RCK domains) in
      prokaryotic K+ transporters and K+ channels. The RCK domain has a Rossmann-fold
      topology with unique positions, not commonly conserved among Rossmann-fold
      proteins, composing a well-conserved salt bridge and a hydrophobic dimer
      interface. Structure-based amino acid sequence alignments and mutational analysis
      are used to demonstrate that an RCK domain is also present and is an important
      component of the gating machinery in eukaryotic large-conductance Ca2+ activated
      K+ channels.

PMID- 11301021
TI  - A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte
      development.
AB  - Compared to neurons, the intracellular mechanisms that control glial
      differentiation are still poorly understood. We show here that oligodendrocyte
      lineage cells express the helix-loop-helix proteins Mash1 and Id2. Although Mash1
      has been found to regulate neuronal development, we found that in the absence of
      Mash1 oligodendrocyte differentiation occurs normally. In contrast, we found that
      overexpression of Id2 powerfully inhibits oligodendrocyte differentiation, that
      Id2 normally translocates out of the nucleus at the onset of differentiation, and
      that absence of Id2 induces premature oligodendrocyte differentiation in vitro.
      These findings demonstrate that Id2 is a component of the intracellular mechanism
      that times oligodendrocyte differentiation and point to the existence of an as
      yet unidentified MyoD-like bHLH protein necessary for oligodendrocyte
      differentiation.

PMID- 11301022
TI  - Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for
      neuronal apoptosis.
AB  - Sympathetic neuronal death induced by nerve growth factor (NGF) deprivation
      requires the macromolecular synthesis-dependent translocation of BAX from the
      cytosol to mitochondria and its subsequent integration into the mitochondrial
      outer membrane, followed by BAX-mediated cytochrome c (cyt c) release. The gene
      products triggering this process remain unknown. Here, we report that BIM, a
      member of the BH3-only proapoptotic subfamily of the BCL-2 protein family, is one
      such molecule. NGF withdrawal induced expression of BIM(EL), an integral
      mitochondrial membrane protein that functions upstream of (or in parallel with)
      the BAX/BCL-2 and caspase checkpoints. Bim deletion conferred protection against
      developmental and induced neuronal apoptosis in both central and peripheral
      populations, but only transiently, suggesting that BIM--and perhaps other BH3
      only proteins--serve partially redundant functions upstream of BAX-mediated cyt c
      release.

PMID- 11301023
TI  - Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and
      inhibiting mitochondrial cytochrome c release.
AB  - Sympathetic neurons require nerve growth factor for survival and die by apoptosis
      in its absence. Key steps in the death pathway include c-Jun activation,
      mitochondrial cytochrome c release, and caspase activation. Here, we show that
      neurons rescued from NGF withdrawal-induced apoptosis by expression of dominant
      negative c-Jun do not release cytochrome c from their mitochondria. Furthermore,
      we find that the mRNA for BIM(EL), a proapoptotic BCL-2 family member, increases
      in level after NGF withdrawal and that this is reduced by dominant-negative c
      Jun. Finally, overexpression of BIM(EL) in neurons induces cytochrome c
      redistribution and apoptosis in the presence of NGF, and neurons injected with
      Bim antisense oligonucleotides or isolated from Bim(-/-) knockout mice die more
      slowly after NGF withdrawal.

PMID- 11301024
TI  - TRPC1 and TRPC5 form a novel cation channel in mammalian brain.
AB  - TRP proteins are cation channels responding to receptor-dependent activation of
      phospholipase C. Mammalian (TRPC) channels can form hetero-oligomeric channels in
      vitro, but native TRPC channel complexes have not been identified to date. We
      demonstrate here that TRPC1 and TRPC5 are subunits of a heteromeric neuronal
      channel. Both TRPC proteins have overlapping distributions in the hippocampus.
      Coexpression of TRPC1 and TRPC5 in HEK293 cells resulted in a novel nonselective
      cation channel with a voltage dependence similar to NMDA receptor channels, but
      unlike that of any reported TRPC channel. TRPC1/TRPC5 heteromers were activated
      by G(q)-coupled receptors but not by depletion of intracellular Ca(2+) stores. In
      contrast to the more common view of the TRP family as comprising store-operated
      channels, we propose that many TRPC heteromers form diverse receptor-regulated
      nonselective cation channels in the mammalian brain.

PMID- 11301025
TI  - Yeast screen for constitutively active mutant G protein-activated potassium
      channels.
AB  - GIRK2 is a major contributor to G protein-activated inward rectifier potassium
      channels in the mammalian brain. How GIRK channels open upon contact with
      Gbetagamma remains unknown. Using a yeast genetic screen to select constitutively
      active mutants from a randomly mutagenized GIRK2 library, we identified five
      gating mutations at four residues in the transmembrane domain. Further
      mutagenesis indicates that GIRK channel opening involves a rotation of the
      transmembrane segments, bringing one of these residues (V188) to a pore-lining
      position in the open conformation. Combined with double-mutant studies, these
      findings suggest that GIRK channels gate by moving from the open conformation
      inferred from our yeast study of Kir2.1 to a closed conformation perhaps
      resembling the known KcsA structure.

PMID- 11301026
TI  - Coupling Gbetagamma-dependent activation to channel opening via pore elements in
      inwardly rectifying potassium channels.
AB  - G protein-coupled inwardly rectifying potassium channels, GIRK/Kir3.x, are gated
      by the Gbetagamma subunits of the G protein. The molecular mechanism of gating
      was investigated by employing a novel yeast-based random mutagenesis approach
      that selected for channel mutants that are active in the absence of Gbetagamma.
      Mutations in TM2 were found that mimicked the Gbetagamma-activated state. The
      activity of these channel mutants was independent of receptor stimulation and of
      the availability of heterologously expressed Gbetagamma subunits but depended on
      PtdIns(4,5)P(2). The results suggest that the TM2 region plays a key role in
      channel gating following Gbetagamma binding in a phospholipid-dependent manner.
      This mechanism of gating in inwardly rectifying K+ channels may be similar to the
      involvement of the homologous region in prokaryotic KcsA potassium channel and,
      thus, suggests evolutionary conservation of the gating structure.

PMID- 11301027
TI  - Calcium dependence of exocytosis and endocytosis at the cochlear inner hair cell
      afferent synapse.
AB  - Release of neurotransmitter at the inner hair cell (IHC) afferent synapse is a
      fundamental step in translating sound into auditory nerve excitation. To study
      the Ca2+ dependence of the underlying vesicle fusion and subsequent endocytosis,
      we combined Ca2+ uncaging with membrane capacitance measurements in mouse IHCs.
      Rapid elevations in [Ca2+]i above 8 microM caused a biphasic capacitance increase
      corresponding to the fusion of approximately 40,000 vesicles. The kinetics of
      exocytosis displayed a fifth-order Ca2+ dependence reaching maximal rates of >3 x
      10(7) vesicle/s. Exocytosis was always followed by slow, compensatory endocytosis
      (tau congruent with 15 s). Higher [Ca2+]i increased the contribution of a faster
      mode of endocytosis with a Ca2+ independent time constant of approximately 300
      ms. These properties provide for rapid and sustained transmitter release from
      this large presynaptic terminal.

PMID- 11301028
TI  - Pair recordings reveal all-silent synaptic connections and the postsynaptic
      expression of long-term potentiation.
AB  - The activation of silent synapses is a proposed mechanism to account for rapid
      increases in synaptic efficacy such as long-term potentiation (LTP). Using
      simultaneous recordings from individual pre- and postsynaptic neurons in
      organotypic hippocampal slices, we show that two CA3 neurons can be connected
      entirely by silent synapses. Increasing release probability or application of
      cyclothiazide does not produce responses from these silent synapses. Direct
      measurement of NMDAR-mediated postsynaptic responses in all-silent synaptic
      connections before and after LTP induction show no change in failure rate,
      amplitude, or area. These data do not support hypotheses that synapse silent
      results from presynaptic factors or that LTP results from increases in
      presynaptic glutamate release. LTP is also associated with an increase in
      postsynaptic responsiveness to exogenous AMPA. We conclude that synapse silence,
      activation, and expression of LTP are postsynaptic.

PMID- 11301029
TI  - Monosynaptic GABAergic signaling from dentate to CA3 with a pharmacological and
      physiological profile typical of mossy fiber synapses.
AB  - Mossy fibers are the sole excitatory projection from dentate gyrus granule cells
      to the hippocampus, where they release glutamate, dynorphin, and zinc. In
      addition, mossy fiber terminals show intense immunoreactivity for the inhibitory
      neurotransmitter GABA. Fast inhibitory transmission at mossy fiber synapses,
      however, has not previously been reported. Here, we show that electrical or
      chemical stimuli that recruit dentate granule cells elicit monosynaptic GABA(A)
      receptor-mediated synaptic signals in CA3 pyramidal neurons. These inhibitory
      signals satisfy the criteria that distinguish mossy fiber-CA3 synapses: high
      sensitivity to metabotropic glutamate receptor agonists, facilitation during
      repetitive stimulation, and NMDA receptor-independent long-term potentiation.
      GABAergic transmission from the dentate gyrus to CA3 has major implications not
      only for information flow into the hippocampus but also for developmental and
      pathological processes involving the hippocampus.

PMID- 11301030
TI  - Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at
      excitatory synapses onto Purkinje cells.
AB  - Brief depolarization of cerebellar Purkinje cells was found to inhibit parallel
      fiber and climbing fiber EPSCs for tens of seconds. This depolarization-induced
      suppression of excitation (DSE) is accompanied by altered paired-pulse
      plasticity, suggesting a presynaptic locus. Fluorometric imaging revealed that
      postsynaptic depolarization also reduces presynaptic calcium influx. The
      inhibition of both presynaptic calcium influx and EPSCs is eliminated by
      buffering postsynaptic calcium with BAPTA. The cannabinoid CB1 receptor
      antagonist AM251 prevents DSE, and the agonist WIN 55,212-2 occludes DSE. These
      findings suggest that Purkinje cells release endogenous cannabinoids in response
      to elevated calcium, thereby inhibiting presynaptic calcium entry and suppressing
      transmitter release. DSE may provide a way for cells to use their firing rate to
      dynamically regulate synaptic inputs. Together with previous studies, these
      findings suggest a widespread role for endogenous cannabinoids in retrograde
      synaptic inhibition.

PMID- 11301031
TI  - Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic
      neurons to presynaptic terminals.
AB  - Endogenous cannabinoids are considered to function as diffusible and short-lived
      modulators that may transmit signals retrogradely from postsynaptic to
      presynaptic neurons. To evaluate this possibility, we have made a paired whole
      cell recording from cultured hippocampal neurons with inhibitory synaptic
      connections. In about 60% of pairs, a cannabinoid agonist greatly reduced the
      release of the inhibitory neurotransmitter GABA from presynaptic terminals. In
      most of such pairs but not in those insensitive to the agonist, depolarization of
      postsynaptic neurons and the resultant elevation of intracellular Ca2+
      concentration caused transient suppression of inhibitory synaptic currents, which
      is mainly due to reduction of GABA release. This depolarization-induced
      suppression was completely blocked by selective cannabinoid antagonists. Our
      results reveal that endogenous cannabinoids mediate retrograde signals from
      depolarized postsynaptic neurons to presynaptic terminals to cause the reduction
      of transmitter release.

PMID- 11301032
TI  - Visual cycle impairment in cellular retinaldehyde binding protein (CRALBP)
      knockout mice results in delayed dark adaptation.
AB  - Mutations in the human CRALBP gene cause retinal pathology and delayed dark
      adaptation. Biochemical studies have not identified the primary physiological
      function of CRALBP. To resolve this, we generated and characterized mice with a
      non-functional CRALBP gene (Rlbp1(-/-) mice). The photosensitivity of Rlbp1(-/-)
      mice is normal but rhodopsin regeneration, 11-cis-retinal production, and dark
      adaptation after illumination are delayed by >10-fold. All-trans-retinyl esters
      accumulate during the delay indicating that isomerization of all-trans- to 11-cis
      retinol is impaired. No evidence of photoreceptor degeneration was observed in
      animals raised in cyclic light/dark conditions for up to 1 year. Albino Rlbp(-/-)
      mice are protected from light damage relative to the wild type. These findings
      support a role for CRALBP as an acceptor of 11-cis-retinol in the isomerization
      reaction of the visual cycle.

PMID- 11301033
TI  - Role of noncovalent binding of 11-cis-retinal to opsin in dark adaptation of rod
      and cone photoreceptors.
AB  - Regeneration of visual pigments of vertebrate rod and cone photoreceptors occurs
      by the initial noncovalent binding of 11-cis-retinal to opsin, followed by the
      formation of a covalent bond between the ligand and the protein. Here, we show
      that the noncovalent interaction between 11-cis-retinal and opsin affects the
      rate of dark adaptation. In rods, 11-cis-retinal produces a transient activation
      of the phototransduction cascade that precedes sensitivity recovery, thus slowing
      dark adaptation. In cones, 11-cis-retinal immediately deactivates
      phototransduction. Thus, the initial binding of the same ligand to two very
      similar G protein receptors, the rod and cone opsins, activates one and
      deactivates the other, contributing to the remarkable difference in the rates of
      rod and cone dark adaptation.

PMID- 11301034
TI  - Eye movements modulate visual receptive fields of V4 neurons.
AB  - The receptive field, defined as the spatiotemporal selectivity of neurons to
      sensory stimuli, is central to our understanding of the neuronal mechanisms of
      perception. However, despite the fact that eye movements are critical during
      normal vision, the influence of eye movements on the structure of receptive
      fields has never been characterized. Here, we map the receptive fields of macaque
      area V4 neurons during saccadic eye movements and find that receptive fields are
      remarkably dynamic. Specifically, before the initiation of a saccadic eye
      movement, receptive fields shrink and shift towards the saccade target. These
      spatiotemporal dynamics may enhance information processing of relevant stimuli
      during the scanning of a visual scene, thereby assisting the selection of saccade
      targets and accelerating the analysis of the visual scene during free viewing.

PMID- 11301035
TI  - The role of spike timing in the coding of stimulus location in rat somatosensory
      cortex.
AB  - Although the timing of single spikes is known to code for time-varying features
      of a sensory stimulus, it remains unclear whether time is also exploited in the
      neuronal coding of the spatial structure of the environment, where nontemporal
      stimulus features are fundamental. This report demonstrates that, in the whisker
      representation of rat cortex, precise spike timing of single neurons increases
      the information transmitted about stimulus location by 44%, compared to that
      transmitted only by the total number of spikes. Crucial to this code is the
      timing of the first spike after whisker movement. Complex, single neuron spike
      patterns play a smaller, synergistic role. Timing permits very few spikes to
      transmit high quantities of information about a behaviorally significant, spatial
      stimulus.

PMID- 11301036
TI  - Impact of active dendrites and structural plasticity on the memory capacity of
      neural tissue.
AB  - We consider the combined effects of active dendrites and structural plasticity on
      the storage capacity of neural tissue. We compare capacity for two different
      modes of dendritic integration: (1) linear, where synaptic inputs are summed
      across the entire dendritic arbor, and (2) nonlinear, where each dendritic
      compartment functions as a separately thresholded neuron-like summing unit. We
      calculate much larger storage capacities for cells with nonlinear subunits and
      show that this capacity is accessible to a structural learning rule that combines
      random synapse formation with activity-dependent stabilization/elimination. In a
      departure from the common view that memories are encoded in the overall
      connection strengths between neurons, our results suggest that long-term
      information storage in neural tissue could reside primarily in the selective
      addressing of synaptic contacts onto dendritic subunits.

PMID- 11301037
TI  - A unified theory of enzyme kinetics based upon the systematic analysis of the
      variations of k(cat), K(M), and k(cat)/K(M) and the relevant DeltaG(0 not equal)
      values-possible implications in chemotherapy and biotechnology.
AB  - To elucidate the kinetic properties of critical enzymatic situations that have
      previously escaped classification, we performed a systematic analysis of all the
      possible variations of the kinetic constants k(cat,) K(M,) and k(sp) =
      k(cat)/K(M,) encompassing all aspects of enzymology. The equation gives a total
      of thirteen theoretically possible cases, comprising the reference case plus 12
      different sets of variations, which can be divided into six principal cases and
      six specular ones. The six relevant cases are examined individually in the
      context of each of the main chapters of enzymology, i.e. as regards mechanism of
      action, specificity of substrate and isoenzyme, reversible and irreversible
      inhibition, and mutation of residues (enzyme evolution and enzyme engineering).
      Some critical cases where k(sp) does not hold as a specificity index are
      classified for the first time. Interestingly, the six possible cases correspond
      to the five known cases of reversible inhibition (competitive, non-competitive,
      incompetitive, mixed competitive/non-competitive, and mixed incompetitive/non
      competitive) plus an additional case of biphasic nature (activation-inhibition),
      which is crucial for a full understanding of specificity and which leads us to
      propose some modification to the definition of enzyme specificity. The systematic
      approach to enzymology outlined herein could find practical applications in
      various sectors of biotechnology, including chemotherapy.

PMID- 11301038
TI  - Suppression of hepatocyte nuclear factor-4alpha by acyl-CoA thioesters of
      hypolipidemic peroxisome proliferators.
AB  - Hepatocyte nuclear factor-4alpha (HNF-4alpha) modulates the expression of liver
      specific genes that control the production (e.g. apolipoprotein [apo] A-I and apo
      B) and clearance (e.g. apo C-III) of plasma lipoproteins. We reported that the
      CoA thioesters of amphipathic carboxylic hypolipidemic drugs (e.g. clofibric acid
      analogues currently used for treating hyperlipidemia in humans and substituted
      long-chain dicarboxylic acids) were formed in vivo, bound to HNF-4alpha,
      inhibited its transcriptional activity, and suppressed the expression of HNF
      4alpha-responsive genes. Hypolipidemic PPARalpha (peroxisome proliferator
      activated receptor alpha) activators that were not endogenously thioesterified
      into their respective acyl-CoAs were shown to be effective in rats but not in
      humans, implying that the hypolipidemic activity transduced by PPARalpha in rats
      was PPARalpha-independent in humans. The suppressed acyl-CoA synthase of
      PPARalpha knockout mice left unresolved the contribution made by the acyl-CoA/HNF
      4alpha pathway to the hypolipidemic effect of PPARalpha agonists in rodents.
      Hence, suppression of HNF-4alpha activity by the CoA thioesters of hypolipidemic
      "peroxisome proliferators" may account for their hypolipidemic activity
      independently of PPARalpha activation by their respective free carboxylates. The
      hypolipidemic activity of peroxisome proliferators is mediated in rats and humans
      by the PPARalpha and HNF-4alpha pathways, respectively.

PMID- 11301039
TI  - Structure-function relationship in the interaction of mastoparan analogs with
      neutrophil NADPH oxidase.
AB  - Mastoparan, an amphiphilic cationic tetradecapeptide was previously shown to
      block activation of the NADPH oxidase in the cell-free system presumably by
      association with a cytosolic component/s of the enzyme. Blockade of oxidase
      activation was now demonstrated in the semirecombinant NADPH oxidase system. The
      structural basis of the inhibitory effect of MP on oxidase assembly was explored
      employing a variety of truncated and specifically substituted synthetic peptide
      analogs. The data indicated that an alpha helical fold, positive net charge,
      hydrophobicity and amphiphilicity were essential for the inhibitory potency and
      that peptide analogs below eleven residues were inactive. To identify the MP
      binding oxidase subunit three different binding assays were carried out utilizing
      free or immobilized recombinant p47-phox, p67-phox, p40-phox and Rac1 in
      conjunction with immobilized MP or soluble (125)I-tyr-MP, respectively. The data
      implicated p67-phox as the main MP-binding component. The binding site on the p67
      phox was localized to the 1-238 aminoterminal fragment of the molecule. NADPH
      oxidase activation supported by this fragment was inhibitable by MP. In addition,
      SH3 domains of p47-phox and p40-phox and the carboxyterminal SH3 domain of p67
      phox exhibited a low affinity towards MP.

PMID- 11301040
TI  - Hydroxypropyl-beta-cyclodextrin as delivery system for thyroid hormones,
      regulating glutathione S-transferase expression in rat hepatocyte co-cultures.
AB  - Thyroid hormones play a role in the regulation of glutathione S-transferase (GST)
      expression. Here, co-cultures of rat hepatocytes with bile duct epithelial cells
      have been used to study the direct effects of both triiodothyronine (T3) and
      thyroxine (T4) on GST activities and proteins. Because T3 and T4 are poorly water
      soluble and organic solvents used to dissolve them often interfere with
      biotransformation pathways, an alternative delivery system namely hydroxypropyl
      beta-cyclodextrin (HPBC) has been applied. Appropriate control cultures contained
      either 0.02 or 0.10% (w/v) HPBC, the concentrations necessary to supply T3 and T4
      (10(-9) to 10(-5) M) to the cells, respectively. No effect of the vehicle HPBC on
      the different GST isoenzyme activities and proteins could be observed. On the
      contrary, after 10 days of co-culture, T3 and T4 decreased GST protein
      concentrations as well as GST activities measured by 1-chloro-2,4-dinitrobenzene
      (broad spectrum), 1,2-dichloro-4-nitrobenzene (Mu class M1/M2-specific) and 7
      chloro-4-nitrobenzo-2-oxa-1,3-diazole (Alpha class A1/2-specific) in a
      concentration-dependent manner. The Alpha class subunits A1/2 and A3, and the Mu
      class subunit M2 were mostly affected. No effect was observed on the Pi class
      enzyme. These findings indicate that a combination of co-cultured hepatocytes
      with an HPBC-based delivery system for hydrophobic compounds represents a
      powerful in vitro tool in drug development.

PMID- 11301041
TI  - Modulation of ligand responses by coupling of alpha(2A)-adrenoceptors to diverse
      G(alpha)-proteins.
AB  - The hypothesis that different signalling may be mediated via a single alpha(2A)
      adrenoceptor (alpha(2A) AR) subtype was investigated by challenging alpha(2) AR
      ligands in combination with diverse recombinant wt, mutant, and chimeric G(alpha)
      proteins. Possible coupling of alpha(2A) AR to endogenous G(alphai/o)-proteins in
      CHO-K1 cells was excluded by measuring pertussis toxin (PTX)-resistant
      [(35)S]GTPgammaS-binding responses as a common functional response to alpha(2A)
      AR activation. (-)-Adrenaline (10 microM) displayed the highest magnitude of
      [(35)S]GTPgammaS-binding response in the co-presence of a PTX-resistant
      G(alphao)Cys(351)Ile protein, whereas a decreased response was obtained with the
      mutant G(alphai1/2)-proteins. Replacement of the last six amino acids at the C
      terminal portion of the G(alphao)-protein by the corresponding amino acid region
      of either the G(alphaz)-, G(alphas)-, G(alphaq)-, or G(alpha15)-protein and co
      expression with the alpha(2A) AR resulted in similar maximal (-)-adrenaline
      mediated [(35)S]GTPgammaS-binding responses with these chimeric G(alphao)
      proteins. The ligands D-medetomidine, BHT 920 (6-allyl-5,6,7,8-tetrahydro-4H
      thiazolo[4,5-d]azepin-2-ylamine) and (+)-RX 811059 (2-(2-ethoxy-2,3-dihydro
      benzo[1,4]dioxin-2-yl)-4,5-dihydro-1H-imidazole) were weakly active or virtually
      inactive at the chimeric G(alphao/s)-, G(alphao/q)-, and G(alphao/15)-proteins in
      contrast to the G(alphao/z)-protein. Furthermore, combining the constitutively
      active mutant Thr(373)Lys alpha(2A) AR with these chimeric G(alphao)-proteins
      enhanced the apparent intrinsic activity of d-medetomidine and BHT 920. A similar
      observation was made using the corresponding fusion proteins, where the
      stoichiometry of the mutant alpha(2A) AR to the chimeric G(alphao)-protein was
      fixed at 1.0. These data indicate that a single ligand may display different
      magnitudes of activation at the alpha(2A) AR subtype coupled to chimeric
      G(alphao) proteins under controlled conditions of alpha(2A) AR: G(alphao)-protein
      expression.

PMID- 11301042
TI  - Stimulation of protein kinase C-dependent and -independent signaling pathways by
      bistratene A in intestinal epithelial cells.
AB  - The marine toxin bistratene A (BisA) potently induces cytostasis and
      differentiation in a variety of systems. Evidence that BisA is a selective
      activator of protein kinase C (PKC) delta implicates PKC delta signaling in the
      negative growth-regulatory effects of this agent. The current study further
      investigates the signaling pathways activated by BisA by comparing its effects
      with those of the PKC agonist phorbol 12-myristate 13-acetate (PMA) in the IEC-18
      intestinal crypt cell line. Both BisA and PMA induced cell cycle arrest in these
      cells, albeit with different kinetics. While BisA produced sustained cell cycle
      arrest in G(0)/G(1) and G(2)/M, the effects of PMA were transient and involved
      mainly a G(0)/G(1) blockade. BisA also produced apoptosis in a proportion of the
      population, an effect not seen with PMA. Both agents induced membrane
      translocation/activation of PKC, with BisA translocating only PKC delta and PMA
      translocating PKC alpha, delta, and epsilon in these cells. Notably, while
      depletion of PKC alpha, delta, and epsilon abrogated the cell cycle-specific
      effects of PMA in IEC-18 cells, the absence of these PKC isozymes failed to
      inhibit BisA-induced G(0)/G(1) and G(2)/M arrest or apoptosis. The cell cycle
      inhibitory and apoptotic effects of BisA, therefore, appear to be PKC-independent
      in IEC-18 cells. On the other hand, BisA and PMA both promoted PKC-dependent
      activation of Erk 1 and 2 in this system. Thus, intestinal epithelial cells
      respond to BisA through activation of at least two signaling pathways: a PKC
      delta-dependent pathway, which leads to activation of mitogen-activated protein
      kinase and possibly cytostasis in the appropriate context, and a PKC-independent
      pathway, which induces both cell cycle arrest in G(0)/G(1) and G(2)/M and
      apoptosis through as yet unknown mechanisms.

PMID- 11301043
TI  - Effects of phorbol ester and dexamethasone treatment on histidine decarboxylase
      and ornithine decarboxylase in basophilic cells.
AB  - Both histamine and polyamines are important for maintaining basophilic cell
      function and viability. The synthesis of these biogenic amines is regulated by
      histidine decarboxylase and ornithine decarboxylase, respectively. In other
      mammalian tissues, an interplay between histamine and polyamine metabolisms has
      been suspected. In this report, the interplay between histamine and ornithine
      derived polyamines was studied in a non-transformed mouse mast cell line (C57.1)
      treated with phorbol ester and dexamethasone, a treatment previously used to
      increase histidine decarboxylase expression in mastocytoma and basophilic
      leukemia. Treatment with phorbol ester and dexamethasone increased histidine
      decarboxylase expression and intracellular histamine levels in C57.1 mast cells
      to a greater extent than those found for other transformed basophilic models. The
      treatment also induced a reduction in ornithine decarboxylase expression,
      intracellular polyamine contents, and cell proliferation. These results indicate
      that the treatment induces a co-ordinate response of polyamine metabolism and
      proliferation in mast cells and other immune-related cells. The decrease in the
      proliferative capacity of mast cells caused by phorbol ester and dexamethasone
      was simultaneous to an increase in histamine production. Our results, together
      with those reported by other groups working with polyamine-treated mast cells,
      indicate an antagonism between histamine and polyamines in basophilic cells.

PMID- 11301044
TI  - Influence of culture system and medium enrichment on sulfotransferase and
      sulfatase expression in male rat hepatocyte cultures.
AB  - The expression of sulfotransferase and steroid sulfatase was studied in rat liver
      using the most promising culture models of hepatocytes, including monolayer
      culture with a pyruvate (30 mM) enriched medium, co-culture with rat epithelial
      cells from primitive biliary origin and collagengel sandwich culture. In the
      latter, addition of dexamethasone (1 microM) to the medium was examined. Phenol
      sulfotransferase enzymes (SULT1) were studied by measuring activities towards 4
      methylphenol and estradiol, hydroxysteroid sulfotransferase (SULT2A) activity was
      determined towards dehydroepiandrosterone (DHEA). Microsomal steroid sulfatase
      activity was measured towards estrone sulfate. Western blot analysis was carried
      out using polyclonal antibodies raised against rat phenol sulfotransferase
      SULT1A1 (ASTIV), estrogen sulfotransferase SULT1E1 (EST) and hydroxysteroid
      sulfotransferase (HST). SULT2A activity towards DHEA was maintained at a high
      level during the whole culture time. In the co-culture it even reached the level
      of freshly isolated cells. Addition of pyruvate had no positive effect on the
      activity measured in monolayer cultures. High SULT1A1 activity towards 4
      methylphenol was found in the co-culture system. In the monolayer culture, the
      activity initially decreased with 35% but was then kept at a constant level,
      while in the sandwich culture low activities were measured. For dexamethasone, an
      inducing effect on the various SULT activities could not be detected.
      Independently of the culture model used, the SULT1E1 activity towards estradiol
      decreased to 20% and 5% of the initial activity after four and seven days of
      culture, respectively. Microsomal steroid sulfatase activity was best maintained
      in collagengel sandwich cultures. During the first four days in culture it
      retained 73% of the initial activity, afterwards it decreased to 40% of the
      activity found in freshly isolated hepatocytes, irrespective of the culture
      conditions. High expectations exist for collagengel sandwich cultures, however,
      in our study the results were rather disappointing. Monolayer is a suitable
      culture model for short-term purposes. For long-term in vitro biotransformation
      studies, co-culture is preferred but is rather complex.

PMID- 11301045
TI  - Inhibition of liver methionine adenosyltransferase gene expression by 3
      methylcolanthrene: protective effect of S-adenosylmethionine.
AB  - Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the
      synthesis of S-adenosylmethionine (AdoMet), the most important biological methyl
      donor. Liver MAT I/III is the product of the MAT1A gene. Hepatic MAT I/III
      activity and MAT1A expression are compromised under pathological conditions such
      as alcoholic liver disease and hepatic cirrhosis, and this gene is silenced upon
      neoplastic transformation of the liver. In the present work, we evaluated whether
      MAT1A expression could be targeted by the polycyclic arylhydrocarbon (PAH) 3
      methylcholanthrene (3-MC) in rat liver and cultured hepatocytes. MAT1A mRNA
      levels were reduced by 50% following in vivo administration of 3-MC to adult male
      rats (100 mg/kg, p.o., 4 days' treatment). This effect was reproduced in a time-
      and dose-dependent fashion in cultured rat hepatocytes, and was accompanied by
      the induction of cytochrome P450 1A1 gene expression. This action of 3-MC was
      mimicked by other PAHs such as benzo[a]pyrene and benzo[e]pyrene, but not by the
      model arylhydrocarbon receptor (AhR) activator 2,3,7,8-tetrachlorodibenzo-p
      dioxin. 3-MC inhibited transcription driven by a MAT1A promoter-reporter
      construct transfected into rat hepatocytes, but MAT1A mRNA stability was not
      affected. We recently showed that liver MAT1A expression is induced by AdoMet in
      cultured hepatocytes. Here, we observed that exogenously added AdoMet prevented
      the negative effects of 3-MC on MAT1A expression. Taken together, our data
      demonstrate that liver MAT1A gene expression is targeted by PAHs, independently
      of AhR activation. The effect of AdoMet may be part of the protective action of
      this molecule in liver damage.

PMID- 11301046
TI  - Inhibition of the preferential binding of actin to the N-terminal hydratase
      domain of the 78-kDa gastrin-binding protein by non-steroidal anti-inflammatory
      drugs and gastrin receptor antagonists.
AB  - The 78 kDa gastrin-binding protein (GBP) is a likely target for the
      antiproliferative effects of gastrin receptor antagonists and non-steroidal anti
      inflammatory drugs (NSAIDs) on colorectal carcinoma cells (Baldwin GS, Murphy VJ,
      Yang Z, and Hashimoto T. J Pharmacol Exp Ther 1998;286:1110-14). This study
      tested the hypotheses that the GBP bound actin, and that the interaction could be
      disrupted by gastrin receptor antagonists and NSAIDs. Binding of actin to the GBP
      was assessed by competition with (125)I-[Nle(15)]-gastrin(2,17) in a covalent
      cross-linking assay, and by comparison of (125)I-actin binding to the N- and C
      terminal GBP domains, which had been expressed independently in E. coli as
      glutathione-S-transferase (GST) fusion proteins. The ability of gastrin receptor
      antagonists and NSAIDs to interfere with the actin-GBP interaction was measured
      by release of (125)I-actin from preformed complexes with the N- and C-terminal
      domain-GST fusion proteins. Actin purified from skeletal muscle or from gastric
      mucosal cytosol competed with (125)I-[Nle(15)]-gastrin(2,17) for binding to the
      GBP with IC(50) values of 2.6 +/- 0.7 microM, and 2.1 +/- 0.7 microM,
      respectively. The amount of (125)I-actin from either source bound to the N
      terminal GBP domain was 8.2 times greater than the amount bound to the C-terminal
      domain. Binding of actin to both domains was inhibited by the gastrin receptor
      antagonists proglumide and benzotript, and by NSAIDs. We conclude that the GBP
      may associate with the cytoskeleton via an interaction between its N-terminal
      domain and actin, and that the association may be disrupted either by gastrin
      receptor antagonists or by NSAIDs.

PMID- 11301047
TI  - Differential effects of pentoxifylline on the hepatic inflammatory response in
      porcine liver cell cultures. Increase in inducible nitric oxide synthase
      expression.
AB  - Pentoxifylline (PTX) has been shown to exert hepatoprotective effects in various
      liver injury models. However, little information is available about the effect of
      PTX on the hepatic acute phase response. In the present study, the effect of PTX
      on a lipopolysaccharide (LPS)-induced acute phase response in primary porcine
      liver cell cultures was examined. During 72 hr of incubation with or without LPS,
      the ability of PTX to influence the secretion of tumour necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6), acute phase proteins, and nitric oxide (NO)
      was assessed. PTX completely inhibited LPS-induced TNF-alpha production and
      attenuated IL-6 only after 48 hr of incubation. In contrast, PTX potentiated NO
      production and the expression of inducible nitric oxide synthase (iNOS) in
      hepatocytes after stimulation with LPS. The increased expression of iNOS and
      concurrent production of NO was also observed when liver cell cultures were
      incubated with dibutyryl cyclic adenosine monophosphate. No effect of PTX on
      acute phase protein secretion was observed during 72 hr of incubation. The
      present results show that PTX differentially affects the endotoxin-induced
      inflammatory response in primary porcine liver cell cultures by suppressing TNF
      alpha and IL-6 while potentiating NO production.

PMID- 11301048
TI  - Kappa-opioid receptor agonist suppression of HIV-1 expression in CD4+
      lymphocytes.
AB  - Synthetic kappa-opioid receptor (KOR) agonists have been shown to suppress HIV-1
      expression in acutely infected macrophages. In the present study, we examined the
      effects of the KOR ligand trans-3,4-dichloro-N-methyl-N[2-(1
      pyrolidinyl)cyclohexyl]benzeneaceamide methanesulfonate (U50,488) on HIV-1
      expression in CD4+ lymphocytes, the main target cell of this virus. When U50,488
      was added to activated CD4+ lymphocytes, HIV-1 expression was inhibited in a
      concentration- and time-dependent manner with maximal suppression (approximately
      60%) at 10(-7) M U50,488. The KOR selective antagonist nor-binaltorphimine (nor
      BNI) had no effect by itself on viral expression but blocked the antiviral
      property of U50,488, suggesting that U50,488 was acting via a KOR-related
      mechanism. Support for the involvement of KOR was provided by the findings that
      34% of activated CD4+ lymphocytes were positive for KOR, using an
      immunofluorescence technique, and that seven additional synthetic KOR ligands
      also inhibited HIV-1 expression. The results of this study broaden understanding
      of the antiviral properties of KOR ligands to include cells outside of the
      nervous system and suggest a potential role for these agents in the treatment of
      HIV-1 infection.

PMID- 11301049
TI  - Regulation of TNFalpha and interleukin-10 production by prostaglandins I(2) and
      E(2): studies with prostaglandin receptor-deficient mice and prostaglandin E
      receptor subtype-selective synthetic agonists.
AB  - To know which receptors of prostaglandins are involved in the regulation of
      TNFalpha and interleukin 10 (IL-10) production, we examined the production of
      these cytokines in murine peritoneal macrophages stimulated with zymosan. The
      presence of PGE(2) or the PGI(2) analog carbacyclin in the medium reduced the
      TNFalpha production to one-half, whereas IL-10 production increased several fold;
      and indomethacin caused the reverse effects, suggesting that endogenous
      prostaglandins may have a regulatory effect on the cytokine production. Among
      prostaglandin E (EP) receptor-selective synthetic agonists, EP2 and EP4 agonists
      caused down-regulation of the zymosan-induced TNFalpha production, but up
      regulation on the IL-10 production; while EP1 and EP3 agonists showed no effect.
      Macrophages harvested from prostaglandin I (IP) receptor-deficient mice showed
      the up- and down-regulatory effects on the cytokine production by the EP2 and EP4
      agonists or PGE(2), but no effect was obtained by carbacyclin. On the contrary,
      macrophages from EP2-deficient mice showed the effect by PGE(2), carbacyclin, and
      the EP4 agonist, but not by the EP2 agonist; and the cells from EP4-deficient
      mice showed the effect by PGE(2), carbacyclin, and EP2 agonist, but not by the
      EP4 agonist. These functional effects of prostaglandins well accorded with the
      mRNA expression of TNFalpha and IL-10 when such expression was examined by the RT
      PCR method. The peritoneal macrophages from normal mice expressed IP, EP2, and
      EP4 receptors, but not EP1 and EP3, when examined by RT-PCR. Thus the results
      suggest that PGI(2) and PGE(2) generated simultaneously with cytokines by
      macrophages treated with zymosan may influence the cytokine production through
      IP, EP2, and EP4 receptors.

PMID- 11301050
TI  - Inhibition of ATP-induced surfactant exocytosis by dihydropyridine (DHP)
      derivatives: a non-stereospecific, photoactivated effect and independent of L
      type Ca2+ channels.
AB  - Purinergic stimulation of surfactant secretion via exocytosis of lamellar bodies
      is mediated by an elevation of the intracellular Ca2+ concentration ([Ca2+](i)).
      We tested the dihydropyridine (DHP) analogues isradipine (+/-enantiomers),
      nifedipine and Bay K 8644 (racemic forms) on ATP-induced surfactant secretion and
      [Ca2+](i) in single type II cells, using FM1-43 and fura-2 fluorescence. None of
      the DHPs (2 microM) had an effect on ATP-induced surfactant secretion in the
      dark. They did, however, inhibit secretion in a concentration-dependent manner
      during illumination, particularly with UV light. This effect was not
      stereospecific, because it was mimicked by (-)-isradipine. In addition, (+)- or (
      )-isradipine, but not nifedipine or Bay K 8644, elicited a slow increase of
      [Ca2+](i) during illumination with UV light, which was reversible by exposure to
      dark. None of the DHPs inhibited the ATP-induced Ca2+ signal. In perforated patch
      clamp experiments, depolarizing voltage steps did not induce L-type Ca2+ (Sr(2+))
      currents, even in the presence of the agonist Bay K 8644 (1 microM). We conclude
      that impairment of ATP-induced surfactant secretion by all tested DHPs and
      alterations of Ca2+ homeostasis by isradipine are photoactivated effects,
      independent of L-type Ca2+ channels.

PMID- 11301051
TI  - Role of G(i)-proteins in norepinephrine-mediated vasoconstriction in rat tail
      artery smooth muscle.
AB  - We showed, in rat de-endothelialised tail artery, that pertussis toxin (PTX) (1
      microg/mL, 2 hr) attenuated norepinephrine (NE)-induced vasoconstriction without
      modifying intracellular calcium concentration [Ca2+](i) mobilisation. We
      suggested the existence of two NE-induced intracellular pathways: a first, which
      would be insensitive to PTX and lead to [Ca2+](i) mobilisation, and a second
      sensitive to PTX and involved in the [Ca2+](i) sensitivity of NE-induced
      contraction. The aim of this study was to demonstrate the existence of the second
      intracellular pathway. PTX-sensitive G(i/o)-proteins in rat tail artery SMC
      membrane were identified by immunoblot and ADP-ribosylation. [(32)P]ADP
      ribosylation of alpha(i/o)-subunits was demonstrated in situ by perfusing rat de
      endothelialised tail artery segments with PTX (1 microg/mL, 2 hr), which
      suggested that G(i/o)-protein inactivation was involved in the reduction by PTX
      of the [Ca2+](i) sensitivity of NE-induced contraction. Coupling between G(i/o)
      proteins and NE receptors was confirmed by the NE-induced increase in G(i/o)
      specific GTPase activity (24.1 +/- 1.9 vs 8.8 +/- 0.4 pmol P(i)/mg protein at 5
      min; P < 0.05 vs basal). [(3)H]Prazosin-binding data showed the presence of a
      heterogeneous alpha(1)-AR population in rat tail artery smooth muscle cells. We
      demonstrated the in vitro coupling between alpha(1A)-AR subtype and alpha(i)
      subunits. In conclusion, we identified, in rat de-endothelialised tail artery, a
      PTX-sensitive G(i/o)-protein-modulated pathway that is coupled to NE receptors
      via alpha(1A)-AR. We suggest that NE stimulates two alpha(1)-AR-mediated
      intracellular pathways: a first, which is mediated by a G(q)-protein and leads to
      [Ca2+](i) mobilisation and contraction, and a second, which is mediated by a G(i)
      protein and is involved in the amplification of the [Ca2+](i) sensitivity of NE
      induced tension.

PMID- 11301052
TI  - The suppression of ornithine decarboxylase expression and cell proliferation at
      the promotion stage of lung tumorigenesis in mice by alpha-tocopheryloxybutyric
      acid.
AB  - It is known that vitamin E inhibits tumor cell growth in vitro irrespective of
      its antioxidative effect. However, it is unclear whether the effect in vitro can
      be applied to the in vivo situation. In order to address this question, we
      estimated if alpha-tocopheryloxybutyric acid (TSE), a non-antioxidative vitamin E
      derivative in vivo, could inhibit cell proliferation during the tumorigenic
      process of lung in mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK), the most potent carcinogen among tobacco-specific nitrosamines.
      TSE administration suppressed the labeling index of the proliferating cell
      nuclear antigen, a marker of cell proliferation at a promotion phase of NNK
      induced lung tumorigenesis in mice. Similarly, TSE administration inhibited the
      elevation of ornithine decarboxylase (ODC) activity and its mRNA at the promotion
      phase. Of four transcription factors contributing to ODC induction, the change in
      the level of the c-Myc/Max-consensus oligonucleotide complex was only
      proportional to the change in ODC mRNA level. These results suggest that vitamin
      E can inhibit cell proliferation linked with ODC induction at the promotion phase
      of lung tumorigenesis irrespective of its antioxidative effect and that
      modulation of the transactivation of the c-Myc/Max complex for the ODC gene by
      TSE in part contributes to the suppression of ODC induction.

PMID- 11301053
TI  - Are we ready for pharmacogenomics in heart failure?
AB  - Heart failure is a major health problem and is associated with a high mortality
      and morbidity. Recently, the role of the genetic background in the onset and
      development of the disease has been evidenced in both heart failure with and
      without systolic dysfunction, and in familial and non-familial forms of this
      condition. Familial forms of dilated cardiomyopathy are more frequent than
      previously thought. Various modes of inheritance and phenotypes have been
      reported and this condition appears genetically highly heterogenous. Five genes
      (dystrophin, cardiac actin, desmin, lamin A/C and delta-sarcoglycan), and
      additional loci, have been identified in families in which dilated cardiomyopathy
      is isolated or associated with other cardiac or non-cardiac symptoms. It has been
      postulated that the molecular defect involved could lead to abnormal interactions
      between cytoskeletal proteins, responsible either for defect in force
      transmission or for membrane disruption. More recently, the identification of
      mutations in genes encoding sarcomeric proteins has led to a second hypothesis in
      which the disease might also result from a force generation defect. In non
      monogenic dilated cardiomyopathy, susceptibility genes (role in the development
      of the disease) and modifier genes (role in the evolution/prognosis of the
      disease) have so far been identified. Some data suggest that the efficacy of
      angiotensin converting enzyme inhibitors, and side-effects, might be related to
      some genetic polymorphisms, such as the I/D polymorphism of the angiotensin
      converting enzyme gene. Although preliminary, these data are promising and might
      be the first step towards application of phamacogenetics in heart failure. This
      is of paramount importance as the medical treatment of heart failure is
      characterized by the need for polypharmacy. One of the major challenges of the
      next millenium, therefore, will be to identify genetic factors which might help
      define responders to major treatment classes, including angiotensin converting
      enzyme inhibitors, beta-adrenoreceptor antagonists, angiotensin AT1 receptor
      antagonists, spironolactone, vasopeptidase inhibitors and endothelin receptor
      antagonists.

PMID- 11301054
TI  - Requirement of additional adenylate cyclase activation for the inhibition of
      human eosinophil degranulation by phosphodiesterase IV inhibitors.
AB  - Human eosinophils contain predominantly phosphodiesterase type IV, but selective
      inhibitors of this isoenzyme fail to inhibit certain eosinophil responses such as
      degranulation. In this study, the effect of activation of adenylate cyclase on
      the ability of several highly selective PDE IV inhibitors to inhibit complement
      C5a-induced O2- release and degranulation of human eosinophils in vitro was
      investigated. All four selective PDE IV inhibitors, N-(3,5-dichloropyrid-4-yl)-3
      cyclopentyl-oxy-4-methoxybenzamide (RP 73401), rolipram, N-(3,5-dichloropyrid-4
      yl)-[1-(4-fluorobenzyl)-5-hydroxy-indol-3-yl]glyoxylacidamide (AWD 12-281) and c
      4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl-r-1-cyclohexane carboxylic acid) (SB
      207499) potently inhibited C5a-induced O2- generation (IC50 = 0.03, 0.42, 0.55
      and 0.86 microM, respectively), but generally failed to inhibit degranulation.
      The only exception was AWD 12-281, which inhibited degranulation (IC50 = 16.2
      microM). In the presence of different AC activators (histamine, salbutamol,
      prostaglandin E2 and forskolin), the PDE IV inhibitors became potent inhibitors
      of degranulation. The interaction between the PDE IV inhibitors and the AC
      activators resulted in a synergistic increase in intracellular levels of
      adenosine 3', 5'-monophosphate (cAMP). These results show that PDE IV inhibitors
      generally require an additional cAMP signal to be able to inhibit eosinophil
      degranulation, and that this signal can be generated via both membrane receptors
      and direct AC activation. This may be relevant to the in vivo effectiveness of
      PDE IV inhibitors in eosinophilic inflammation.

PMID- 11301055
TI  - Enhancement of arachidonic acid release and prostaglandin F(2alpha) formation by
      Na3VO4 in PC12 cells and GH3 cells.
AB  - Both activation of phospholipase A2 causing arachidonic acid release and tyrosine
      phosphorylation have been proposed to be involved in neuronal functions.
      Previously, we reported that orthovanadate (Na3VO4), an inhibitor of tyrosine
      phosphatases, stimulated tyrosine phosphorylation in proteins and enhanced Ca2+
      induced noradrenaline release in rat pheochromocytoma PC12 cells. However, the
      role of tyrosine phosphorylation on phospholipase A2 activity and/or arachidonic
      acid release in neuronal cells has not been well established. The effects of
      Na3VO4 on arachidonic acid release and prostaglandin F(2alpha) formation were
      investigated in two types of neuronal cell lines. In PC12 cells, addition of
      Na3VO4 stimulated [3H]arachidonic acid release and prostaglandin F(2alpha)
      formation in a concentration-dependent manner. Co-addition of 5 mM Na3VO4
      enhanced ionomycin-stimulated [3H]arachidonic acid release. Na3VO4 also enhanced
      ionomycin-stimulated [3H]arachidonic acid release from GH3 cells, a clonal strain
      from rat anterior pituitary. These findings suggest that the tyrosine
      phosphorylation pathway regulates arachidonic acid release by phospholipase A2
      and prostaglandin F(2alpha) formation in neuronal cells.

PMID- 11301056
TI  - Angiotensin receptor in the heart of Bothrops jararaca snake.
AB  - Angiotensin II interacts with specific cell surface angiotensin AT1 and AT2
      receptors and, in some vertebrates, with an atypical angiotensin AT receptor.
      This study was designed to characterize the angiotensin receptor in the heart of
      Bothrops jararaca snake. A specific and saturable angiotensin II binding site was
      detected in cardiac membranes and yielded Kd=7.34+/-1.41 nM and B(max)=72.49+/-18
      fmol/mg protein. Competition-binding studies showed an angiotensin receptor with
      low affinity to both angiotensin receptor antagonists, losartan (2-n-butyl-4
      chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole)
      and PD123319 ((s)-1-(4-[dimethylamino]-3-methylphenyl)methyl-5-(diphenylacetyl)
      4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylate). Studies on the
      intracellular signaling pathways showed that phospholipase C/inositol phosphate
      breakdown and adenylylcyclase/cyclic AMP generation were not coupled with this
      angiotensin receptor. An adenylylcyclase enzyme sensitive to forskolin was
      detected. The results indicate the presence of an angiotensin receptor in the
      heart of B. jararaca snake pharmacologically distinct from angiotensin AT1 and
      AT2 receptors. It seems to belong to a new class of angiotensin receptors, like
      some other atypical angiotensin AT receptors that have already been described.

PMID- 11301057
TI  - Inhibition of the myeloperoxidase chlorinating activity by non-steroidal anti
      inflammatory drugs investigated with a human recombinant enzyme.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) were investigated for their
      ability to affect the chlorinating activity of human myeloperoxidase and to
      scavenge HOCl, the main myeloperoxidase system product. Fourteen drugs
      representative of various NSAIDs families were tested with the chlorination of
      taurine used as a detection system. All were unable to inhibit taurine
      chlorination in a system without myeloperoxidase. In contrast, most of them
      induced a dose-dependent inhibition of the taurine chlorination mediated by a
      myeloperoxidase/H2O2/Cl- system. This took place at variable drug concentrations
      and IC50 were calculated. The inhibitory effect was therefore due to a direct
      interaction with the enzyme rather than to HOCl scavenging. A spectroscopic
      method used to measure the myeloperoxidase compound II lifetime in presence of
      the different drugs showed that all the drugs, which inhibited chlorination
      activity were able to induce accumulation of compound II. The extent of
      chlorinating activity inhibition (IC50) was inversely related to the duration of
      the block of enzyme in compound II form. This further demonstrates that
      myeloperoxidase is an interesting target for anti-inflammatory therapy. The
      recombinant myeloperoxidase used for the first time in this kind of study was as
      convenient for pharmacological purposes as the purified one.

PMID- 11301058
TI  - Neuropeptide FF receptors couple to a cholera toxin-sensitive G-protein in rat
      dorsal raphe neurones.
AB  - In rat dorsal raphe neurones, nociceptin (300 nM) reduced the peak [Ca(2+)](i)
      transient, triggered by depolarization, by 36.7+/-1.8% (n=46). This effect of
      nociceptin decreased to 16.7+/-2.9% (n=18) after pre-treatment of the neurones
      with pertussis toxin (5 microg/ml, 2-6 h) but was unchanged (37.4+/-2.1%, n=44)
      after pre-incubation with cholera toxin (5 microg/ml, 2-6 h). This suggests that,
      in dorsal raphe neurones, the ORL1 receptor couples to inhibitory (G(i/o)) G
      proteins. The neuropeptide FF analogue, [D-Tyr1, (N-Me)Phe(3)]neuropeptide FF
      (10, 100, 1000 nM), acted as an anti-opioid and reduced the effect of nociceptin
      (300 nM, 30 s) by 62.0+/-3.3% (n=28). Following pre-incubation with cholera toxin
      (5 microg/ml, 2-6 h) [D-Tyr1, (N-Me)Phe3] neuropeptide FF was unable, at the
      three concentrations tested, to block nociceptin activity. We conclude that, in
      rat dorsal raphe neurones, neuropeptide FF receptors couple to stimulatory G
      proteins (Gs).

PMID- 11301059
TI  - Characterisation using FLIPR of human vanilloid VR1 receptor pharmacology.
AB  - A full pharmacological characterisation of the recently cloned human vanilloid
      VR1 receptor was undertaken. In whole-cell patch clamp studies, capsaicin (10
      microM) elicited a slowly activating/deactivating inward current in human
      embryonic kidney (HEK293) cells stably expressing human vanilloid VR1 receptor,
      which exhibited pronounced outward rectification (reversal potential -2.1+/-0.2
      mV) and was abolished by capsazepine (10 microM). In FLIPR-based Ca(2+) imaging
      studies the rank order of potency was
      resiniferatoxin>olvanil>capsaicin>anandamide, and all were full agonists.
      Isovelleral and scutigeral were inactive (1 nM-30 microM). The potencies of
      capsaicin, olvanil and resiniferatoxin, but not anandamide, were enhanced 2- to 7
      fold at pH 6.4. Capsazepine, isovelleral and ruthenium red inhibited the
      capsaicin (100 nM)-induced Ca(2+) response (pK(B)=6.58+/-0.02, 5.33+/-0.03 and
      7.64+/-0.03, respectively). In conclusion, the recombinant human vanilloid VR1
      receptor stably expressed in HEK293 cells acted as a ligand-gated, Ca(2+)
      permeable channel with similar agonist and antagonist pharmacology to rat
      vanilloid VR1 receptor, although there were some subtle differences.

PMID- 11301060
TI  - Release and aggregation of cytochrome c and alpha-synuclein are inhibited by the
      antiparkinsonian drugs, talipexole and pramipexole.
AB  - Recently, it has been shown that release of cytochrome c from the mitochondria to
      the cytosol is required for activation of the caspase-3-dependent cascade in
      apoptosis, and also for alpha-synuclein aggregation. In the present study, we
      examined the effects of talipexole and pramipexole on the release of cytochrome c
      and alpha-synuclein, their aggregations, and activation of caspases. Treatment of
      human neuroblastoma SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP(+), 1 mM)
      induced the first event, which was the release of cytochrome c from the
      organellar fraction to the cytosolic fraction, then came the DNA fragmentation,
      and caused the last event, which was the accumulation of alpha-synuclein protein
      in the cytosolic fraction. Talipexole and pramipexole at low concentration (0.1-1
      mM) significantly inhibited the accumulation of cytochrome c or alpha-synuclein
      in the cytosolic fraction. These drugs at high concentration (3-10 mM) inhibited
      in vitro aggregation of cytochrome c by hydrogen peroxide or that of alpha
      synuclein by cytochrome c and hydrogen peroxide. In addition, in vitro activation
      of caspase-3 induced by cytochrome c and/or dATP was also inhibited by drugs at
      high concentration (5-10 mM). These results suggest that talipexole and
      pramipexole may have protective effects against the neurodegeneration, which is
      induced by intracellular accumulation of cytochrome c and alpha-synuclein.

PMID- 11301061
TI  - Regulation of serotonin transporter gene expression in human glial cells by
      growth factors.
AB  - The aims of this study were to identify monoamine transporters expressed in human
      glial cells, and to examine the regulation of their expression by stress-related
      growth factors. The expression of serotonin transporter mRNA was detected by
      reverse transcriptase-polymerase chain reaction in normal human astrocytes,
      whereas the dopamine transporter (DAT) and the norepinephrine transporter (NET)
      were not detected. The cDNA sequence of the "glial" serotonin transporter in
      astrocytes was consistent with that reported for the "neuronal" serotonin
      transporter (SERT). Moreover, we also demonstrated SERT expression in glial
      fibrillary acidic protein-positive cells by immunocytochemical staining in normal
      human astrocytes. Serotonin transporter gene expression was also detected in
      glioma-derived cell lines (A172, KG-1-C and KGK). Addition of basic fibroblast
      growth factor (bFGF) or epidermal growth factor (EGF) for 2 days increased
      serotonin transporter gene expression in astrocytes and JAR (human
      choriocarcinoma cell line). Basic fibroblast growth factor, but not epidermal
      growth factor, increased specific [3H]serotonin uptake in astrocytes in a time (1
      4 days)- and concentration (20-100 ng/ml)-dependent manner. The expression of
      genes for basic fibroblast growth factor and epidermal growth factor receptors
      was detected in astrocytes. These findings suggest that the expression of the
      serotonin transporter in human glial cells is positively regulated by basic
      fibroblast growth factor.

PMID- 11301062
TI  - Binding of prostaglandins to human PPARgamma: tool assessment and new natural
      ligands.
AB  - The peroxisome proliferator-activated receptors (PPAR) form a family of nuclear
      receptors with a wide variety of biological roles from adipogenesis to
      carcinogenesis. More ligands (agonist and antagonist) are needed to explore the
      multiple functions of PPAR, particularly PPARgamma. In order to complete such
      ligand screening, a binding test should be assessed versus the classical
      transactivation reporter gene assay. In the present work, the full-length human
      PPARgamma protein as well as its ligand binding domain portion were expressed in
      Escherichia coli. Bacterial membrane preparations expressing those constructs
      were characterized using a classical binding competition assay [3H]rosiglitazone
      as the radioligand. When the receptor preparations were soluble, binding had to
      be measured with a new alternative method. The systems were assessed using a
      series of reference PPAR (alpha, beta and gamma) ligands. The full-length human
      PPARgamma fused to glutathione-S-transferase, expressed in E. coli and tested as
      a bacterial membrane-bound protein led to the most accurate results when compared
      to the literature. Furthermore, in an attempt to complete the panel of natural
      PPARgamma ligands, 29 commercially available prostaglandins were screened in the
      binding assay. Prostaglandins H(1) and H(2) were found to be modest ligands,
      however as potent as 15Delta(12-14 )prostaglandin J(2). These results were
      confirmed in the classical transactivation assay. The fact that these three
      prostaglandins were equally potent, suggests new pathways of PPARgamma-linked
      gene activation.

PMID- 11301063
TI  - The role of minoxidil on endogenous opioid peptides in the spinal cord: a
      putative co-agonist relationship between K-ATP openers and opioids.
AB  - ATP-gated K(+) channel openers produce antinociception that is attenuated by
      opioid receptor antagonists, indicating K-ATP openers produce antinociception, in
      part, via the release of endogenous opioid peptides. Utilizing the spinal
      perfusion method, male Sprague-Dawley rats were administered minoxidil
      intrathecally (i.t.) at doses ranging from 12.5 to 200 microg/rat for 3 min,
      tested for antinociception using the tail-flick test, and perfused with
      artificial cerebrospinal fluid (aCSF) to collect endogenous opioid peptides.
      Endogenous opioid peptide levels were measured by radioimmunoassay. Naltrindole,
      a delta-opioid receptor antagonist, at 4 mg/kg, subcutaneously (s.c.), blocked
      minoxidil-induced antinociception. beta-Funaltrexamine, a mu-opioid receptor
      antagonist, at 100 microg/rat, partially blocked minoxidil, whereas the kappa
      opioid receptor antagonist nor-binaltorphimine, at a dose of 100 microg/rat, did
      not attenuate minoxidil. Although antagonists of the mu- and delta-opioid
      receptor attenuated minoxidil-induced antinociception, there was no increase in
      beta-endorphin, an endogenous ligand with affinity for both micro- and delta
      opioid receptors or [Leu(5)]enkephalin, an endogenous ligand with affinity for
      delta-opioid receptors.

PMID- 11301064
TI  - Blockade by agmatine of catecholamine release from chromaffin cells is unrelated
      to imidazoline receptors.
AB  - The blockade of exocytosis induced by the putative endogenous ligand for
      imidazoline receptors, agmatine, was studied by using on-line measurement of
      catecholamine release in bovine adrenal medullary chromaffin cells. Agmatine
      inhibited the acetylcholine-evoked release of catecholamines in a concentration
      dependent manner (IC(50)=366 microM); the K(+)-evoked release of catecholamines
      was unaffected. Clonidine (100 microM) and moxonidine (100 microM) also inhibited
      by 75% and 50%, respectively, the acetylcholine-evoked response. In cells voltage
      clamped at -80 mV, the intermittent application of acetylcholine pulses elicited
      whole-cell inward currents (I(ACh)) that were blocked 63% by 1 mM agmatine. The
      onset of blockade was very fast (tau(on) = 31 ms); the recovery of the current
      after washout of agmatine also occurred very rapidly (tau(off = 39 ms). Efaroxan
      (10 microM) did not affect the inhibition of I(ACh) elicited by 1 mM agmatine.
      I(ACh) was blocked 90% by 100 microM clonidine and 50% by 100 microM moxonidine.
      The concentration-response curve for acetylcholine to elicit inward currents was
      shifted to the right in a non-parallel manner by 300 microM agmatine. The
      blockade of I(ACh) caused by agmatine (100 microM) was similar at various holding
      potentials, around 50%. When intracellularly applied, agmatine did not block
      I(ACh). At 1 mM, agmatine blocked I(Na) by 23%, I(Ba) by 14%, I(K(Ca)) by 16%,
      and I(K(VD)) by 18%. In conclusion, agmatine blocks exocytosis in chromaffin
      cells by blocking nicotinic acetylcholine receptor currents. In contrast to
      previous views, these effects seem to be unrelated to imidazoline receptors.

PMID- 11301065
TI  - The anxiolytic effect of allopregnanolone is associated with gonadal hormonal
      status in female rats.
AB  - The behavioural display in the plus-maze, an established experimental model of
      anxiety, was studied in rats injected into the lateral brain ventricle (i.c.v.)
      with the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone).
      Female rats under different gonadal hormonal status were chosen. Allopregnanolone
      enhanced exploration of the open arms in both estrous rats and ovariectomized
      estrogen and progesterone primed rats. No effect was observed in diestrous 1 and
      ovariectomized not-primed rats. In all cases, the plus-maze locomotor-exploratory
      behaviour was not affected by allopregnanolone. The GABA(A) receptor antagonist,
      bicuculline (9.8 microM i.c.v.) reversed the allopregnanolone action in the
      ovariectomized primed rats. When bicuculline was injected i.c.v. in conjunction
      with allopregnanolone, the anxiogenic effect of bicuculline was reversed by the
      highest dose (25 microM) of allopregnanolone only. These results suggest that
      allopregnanolone exerts an anxiolytic action interacting with the GABA(A)
      receptor in an estrogen-dependent manner.

PMID- 11301066
TI  - Nicotine-induced behavioral disinhibition and ethanol preference correlate after
      repeated nicotine treatment.
AB  - This study investigated the effects of repeated daily nicotine (0.35 mg/kg; 15
      days) treatment on behavioral inhibition and locomotor activity in the elevated
      plus-maze and on voluntary ethanol consumption. When challenged with nicotine
      before the test, rats pretreated with repeated nicotine spent more time on and
      made more entries onto the open arms of an elevated plus-maze than did vehicle
      pretreated animals. The ethanol preference and intake, measured during 3 h after
      a nicotine injection, was also higher in the nicotine-pretreated animals. In
      ethanol consumption experiments, there was a positive correlation between the %
      time and % entries made onto open arms vs. the ethanol preference and intake.
      However, no correlation between the total number of entries made in the elevated
      plus-maze and the measures of ethanol consumption was observed. These findings
      suggest that the ability of repeated nicotine administration to increase ethanol
      consumption is related to development of a nicotine-induced reduction of
      inhibitory control rather than development of locomotor sensitization.

PMID- 11301067
TI  - Weak vasoconstrictor activity of melatonin in human umbilical artery: relation to
      nitric oxide-scavenging action.
AB  - We evaluated the nitric oxide (NO)-scavenging property of melatonin, demonstrated
      in a recent in vitro study, on vascular reactivity in the human umbilical artery.
      Helical sections of human umbilical artery were prepared following elective
      Cesarean deliveries near term. Changes in maximal tension induced by
      prostaglandin F(2 alpha)(5 x 10(-5) M) were measured in artery sections with an
      intact endothelium. Melatonin at concentrations higher than 10(-6) M increased
      prostaglandin F(2 alpha)-induced vascular tension. The vasospastic effect of
      melatonin was much less than that of L-N(G)-monomethylarginine (L-NMA, 2 x 10(-4)
      M), an inhibitor of NO synthesis (2.8+/-1.4%, 9.1+/-1.7%, 16.5+/-2.5%, and 29.6+/
      5.9% of the L-NMA effect at melatonin concentrations of 10(-8), 10(-7), 10(-6),
      and 10(-5) M, respectively). Removal of the endothelium significantly reduced the
      vasoconstrictive effect of melatonin. Treatment with L-NMA (2 x 10(-4) M) prior
      to addition of prostaglandin F(2 alpha) also significantly reduced the
      vasoconstrictive effect of melatonin (10(-5) M). Treatments with melatonin (10(
      5) M) did not affect calcium ionophore A 23187-induced relaxation or 5
      hydroxytryptamine-induced constriction. The findings indicate that melatonin may
      potentiate vascular tension in human umbilical artery by scavenging endogenous
      endothelial NO, but not by inhibiting NO synthesis. However, the NO-scavenging
      vasoconstrictive effect of melatonin may be negligible at physiologic
      concentrations and very weak at pharmacologic concentrations below 10(-7) M.

PMID- 11301068
TI  - The effects of tubulin-binding agents on stretch-induced ventricular arrhythmias.
AB  - Stretch-activated ion channels have been identified as transducers of
      mechanoelectric coupling in the heart, where they may play a role in
      arrhythmogenesis. The role of the cytoskeleton in ion channel control has been a
      topic of recent study and the transmission of mechanical stresses to stretch
      activated channels by cytoskeletal attachment has been hypothesized. We studied
      the arrhythmogenic effects of stretch in 16 Langendorff-perfused rabbit hearts in
      which we pharmacologically manipulated the microtubular network of the cardiac
      myocytes. Group 1 (n=5) was treated with colchicine, which depolymerizes
      microtubules, and Group 2 (n=6) was treated with taxol, which polymerizes
      microtubules. Stretch-induced arrhythmias were produced by transiently increasing
      the volume of a fluid-filled left ventricular balloon with a volume pump driven
      by a computer-controlled stepper motor. Electrical events were recorded by a
      contact electrode which provided high-fidelity recordings of monophasic action
      potentials and stretch-induced depolarizations. The probability of eliciting a
      stretch-induced arrhythmia increased (0.22+/-0.11 to 0.62+/-0.19, p=0.001) in
      hearts treated with taxol (5 microM), whereas hearts treated with colchicine (100
      microM) showed no statistically significant change. We conclude that
      proliferation of microtubules increased the arrhythmogenic effect of transient
      left ventricle diastolic stretch. This result indicates a possible mode of
      arrhythmogenesis in chemotherapeutic patients and patients exhibiting
      uncompensated ventricular hypertrophy. The data would indicate that the
      cytoskeleton represents a possible target for antiarrhythmic therapies.

PMID- 11301069
TI  - Effects of phosphodiesterase inhibitors on hypoxic pulmonary vasoconstriction.
      Influence of K(+) channels and nitric oxide.
AB  - We studied the relaxant effects of the cyclic nucleotide phosphodiesterase
      inhibitors theophylline (non-selective), rolipram (type IV, 3',5'-cyclic
      monophosphate (cAMP)-specific) and zaprinast (type V, 3',5'-cyclic monophosphate
      (cGMP)-specific) on the hypoxic vasoconstriction in the isolated perfused rat
      lung and the involvement of K(+) channels and nitric oxide (NO) in these effects.
      K(+) channels were inhibited by glibenclamide, charybdotoxin, apamin and 4
      aminopyridine and nitric oxide synthase by L-N(G)-nitroarginine methyl ester (L
      NAME). Hypoxic ventilation produced a significant pressure response. L-NAME and 4
      aminopyridine increased this response. Rolipram, zaprinast and theophylline
      shared the ability to oppose the hypoxic pulmonary vasoconstriction. The order of
      potency was zaprinast>rolipram>theophylline. Glibenclamide partially inhibited
      the relaxant effects of rolipram and theophylline. Charybdotoxin inhibited the
      dilator response to rolipram. Apamin inhibited partially the vasodilation induced
      by rolipram and zaprinast. 4-Aminopyridine inhibited partially the relaxant
      effects of theophylline. L-NAME failed to block the effects of the three
      compounds. These data illustrate different pharmacological profiles according to
      the phosphodiesterase inhibitors and support the potential interest of selective
      inhibitors as relaxant agents in pulmonary vessels.

PMID- 11301070
TI  - Clozapine-induced Fos-protein expression in rat forebrain regions: differential
      effects of adrenalectomy and corticosterone supplement.
AB  - Unlike classical antipsychotic drugs, clozapine activates the hypothalamo
      pituitary-adrenal axis and induces a specific regional pattern of Fos-protein
      expression in the rat forebrain. Whether corticosterone plays a role in the
      clozapine-induced Fos response is the subject of this study. Some rats were
      adrenalectomized and in a number, including intact animals, a corticosterone
      pellet (100 mg s.c.) was implanted; after 1 week, a single dose of clozapine (20
      mg kg(-1) i.p.) was administered. The clozapine-induced Fos response was not
      affected by adrenalectomy, apart from the nucleus accumbens shell, the
      subfornical organ and the supraoptic nucleus; there was an increased response in
      the nucleus accumbens shell, while other regions showed less Fos
      immunoreactivity. Implantation of the corticosterone pellet in both sham-operated
      and adrenalectomized animals, reduced the clozapine-induced Fos responses
      strongly in the hypothalamic paraventricular nucleus, the subfornical organ and
      possibly in the prefrontal cortex; in the supraoptic nucleus, this effect was
      seen only in intact animals. The effect of clozapine on plasma corticosterone
      levels was also diminished by supplemental corticosterone treatment. These
      results imply that the effects of clozapine are partially dependent upon
      hypothalamo-pituitary-adrenal axis integrity and activation. The efficacy of
      clozapine in the treatment of polydipsia and hyponatremia in chronic psychiatric
      patients may involve clozapine-mediated activation of the cellular activity in
      the subfornical organ.

PMID- 11301071
TI  - (+/-)-SM 21 attenuates the convulsive and locomotor stimulatory effects of
      cocaine in mice.
AB  - Cocaine interacts with sigma receptors at physiologically relevant
      concentrations. While earlier studies demonstrate that antagonism of sigma(1)
      receptors attenuates the behavioral actions of cocaine, the contribution of
      sigma(2) receptors is unclear. Therefore, in the present study, 3 alpha-tropanyl
      2-(4-chlorophenoxy)butyrate ((+/-)-SM 21), a compound with high and preferential
      affinity for sigma(2) receptors, was tested for its ability to attenuate cocaine
      induced behaviors. Pre-treatment of Swiss Webster mice with (+/-)-SM 21
      significantly attenuated cocaine-induced convulsions and locomotor activity.

PMID- 11301072
TI  - Gradient refractive index of the crystalline lens of the Black Oreo Dory
      (Allocyttus Niger): comparison of magnetic resonance imaging (MRI) and laser ray
      trace methods.
AB  - The gradient refractive index of the crystalline lens in the Black Oreo Dory
      (Allocyttus Niger) was determined using two methods; an optimisation program
      based on finite ray-tracing and the path of laser beams through the lens, and
      magnetic resonance imaging (MRI) and the linear relationship between refractive
      index and nuclear transverse relaxation rates. The methods showed good agreement
      in the cortical zone of the lens, but the lack of free water in the core of the
      lens made MRI measurement impossible in this region. The laser-optimisation
      method gave mean values of 1.368 and 1.543 for the surface and core refractive
      indices respectively, with a radial distribution for the gradient refractive
      index given by n(r)=1.543-0.121r2-0.033r4-0.021r6.

PMID- 11301073
TI  - A transition between eye and object rivalry determined by stimulus coherence.
AB  - Two orthogonal patterns presented to the two eyes, respectively, are perceived as
      alternating in time, a phenomenon often assumed to reflect competition between
      neuronal activities corresponding to the two eyes, presumably in the primary
      visual cortex. Recent evidence supports a competition between neuronal activities
      corresponding to the two patterns (objects) at some higher cortical processing
      stage after inputs from the two eyes have converged. Here, using textures made of
      Gabor signals, we present psychophysical data showing that the level of visual
      processing at which competition takes place and is resolved, is determined by the
      degree of stimulus coherence. Moreover, depending on stimulus parameters,
      competition may occur at several levels of processing at the same time.

PMID- 11301074
TI  - Detecting shape deformation of moving patterns.
AB  - This study measured thresholds for the discrimination of rigidly and nonridgidly
      rotating patterns in two dimensions. The stimuli employed were closed contours
      created by the sum of two 'radial frequency' components and sensitivity to their
      deformation was measured as a function of the difference in the angular
      velocities of the components. Results show that thresholds do not depend on the
      specific shape of the pattern. To quantify the influence of local computations
      versus global pooling, thresholds were measured with parts of the pattern covered
      by (invisible) pie-shaped apertures. One finds thresholds are not simply a
      function of the total amount of pattern visible but exhibit a dependence on the
      number of apertures. Moreover, sensitivity to deformation could neither be fully
      explained on the basis of local computations nor by linear global summation. A
      simultaneous masking paradigm was employed to elucidate potential mechanisms
      involved in the computation of deformation. While 1D masks (horizontal gratings
      and translating random dots) only marginally elevate thresholds, rotating and
      expanding motion significantly impairs sensitivity. This indicates that detectors
      tuned to radial and circular motion are involved in the computation of shape
      deformation.

PMID- 11301075
TI  - The role of spatial frequency in color induction.
AB  - Color induction was measured for test and inducing chromaticities presented in
      spatial square-wave alternation, with spatial frequencies of 0.7, 4.0, 6.0 and
      9.0 cpd. Observers matched the test chromaticities to a rectangular matching
      field using haploscopic presentation. Data were collected and analyzed within the
      framework of a cone chromaticity space, allowing analysis of spatial frequency
      effects on post-receptoral spectral opponent pathways. Assimilation, a shift of
      chromaticity toward the inducing chromaticity, was found at the highest spatial
      frequency (9.0 cpd). Contrast, a shift of chromaticity away from the inducing
      chromaticity, occurred at the lowest spatial frequency (0.7 cpd). The spatial
      frequency at the transition point from assimilation to contrast was near 4 cpd,
      independent of the cone axis. Assimilation was unaffected by the presence of a
      neutral surround and could be described by a spread light model. Contrast was
      reduced in the presence of a neutral surround. The data suggested that retinal
      contrast signals are important determinants in the perception of chromatic
      contrast.

PMID- 11301076
TI  - Dynamics of contour integration.
AB  - To determine the dynamics of contour integration the temporal properties of the
      individual contour elements were varied as well as those of the contour they
      form. A temporal version of a contour integration paradigm (Field, D. J., Hayes,
      A., & Hess, R. F. (1993) Vision Research, 33, 173-193) was used to assess these
      two temporal dynamics as a function of the contrast of individual elements and
      the curvature of the contour. The results show that the dynamics of contour
      integration are good when the contrast of the individual elements is modulated in
      time (10-30 Hz), but are poor when contour linking per se is temporally modulated
      (1-12 Hz). The dynamics of contour linking is not dependent on the absolute
      contrast of the linking elements, so long as they are visible, but does vary with
      the curvature of the contour. For straight contours, temporal resolution is
      around 6-12 Hz but falls to around 1-2 Hz for curved contours.

PMID- 11301077
TI  - Dependency of reaction times to motion onset on luminance and chromatic contrast.
AB  - We measured reaction times for detecting the onset of motion of sinusoidal
      gratings of 1 c/deg, modulated in either luminance or chromatic contrast, caused
      to move abruptly at speeds ranging from 0.25 to 10 deg/s (0.25-10 Hz). At any
      given luminance or chromatic contrast, RTs varied linearly with temporal
      periodicity (r2 congruent with 0.97), yielding a Weber fraction of period. The
      value of the Weber fraction varied inversely with contrast, differently for
      luminance and chromatic contrast. The results were well simulated with a simple
      model that accumulated change in contrast over time until a critical threshold
      had been reached. Two crucial aspects of the model are a second-stage temporal
      integration mechanism, capable of accumulating information for periods of up to 2
      s, and contrast gain control, different for luminance than for chromatic stimuli.
      The contrast response for luminance shows very low semi-saturating contrasts and
      high gain, similar to LGN M-cells and cells in MT; that for colour shows high
      semi-saturating contrasts and low gain, similar to LGN P-cells. The results
      suggest that motion onset for luminance and chromatic gratings are detected by
      different mechanisms, probably by the magno- and parvo-cellular systems.

PMID- 11301078
TI  - Infant direction discrimination thresholds.
AB  - Although adults can detect direction differences as small as 1 arc degree, the
      ability of infants to discriminate direction of motion is less clear. This study
      measures the precision with which 6-, 12-, and 18-week-old infants discriminate
      direction of motion. Infants viewed random dot kinematograms in which a direction
      difference between the target and background dots defined a circular target. The
      target was then placed into continuous motion. An FPL paradigm was used to assess
      infants' preference for the target as a function of the direction difference
      between the target and background dots. Direction discrimination thresholds with
      a moving target were indeterminate at 6 weeks of age, 22 degrees at 12 weeks of
      age and 17 degrees at 18 weeks of age. This precision was maintained across
      different testing conditions. However, performance dropped markedly when dot
      motion was presented within a flickering stationary target. It was concluded that
      infants can make relatively fine discriminations of motion direction if given an
      engaging stimulus.

PMID- 11301079
TI  - Interaction between first- and second-order orientation channels revealed by the
      tilt illusion: psychophysics and computational modelling.
AB  - This paper examines the interaction between first- and second-order contours in
      the orientation domain. Using the simultaneous tilt illusion (TI), we show that
      the apparent rotation of a vertical test grating away from that of a surrounding
      inducing grating (repulsion effect) occurs when both the inducing and test
      grating are either first- or second-order. Furthermore, a significant repulsion
      effect is obtained when a first-order inducing grating surrounds a second-order
      test. If lateral inhibitory interactions between populations of orientation
      selective neurons provides a plausible explanation for orientation repulsion
      effects [Blakemore, C. B. Carpenter, R. H. S. & Georgeson, M. A. (1970) Nature,
      228, 37-39], it is likely that the cue-invariant mechanisms that encodes the
      orientation of first- and second-order contours also exhibit inhibitory
      interactions. A two-channel computational model of orientation encoding is
      presented where one channel encodes only first-order stimuli while the second
      channel encodes both first- and second-order contours. In addition to predicting
      the orientation repulsion effects we observed, the model also provides a
      functional account of orientation attraction effects in terms of the responses of
      populations of orientation-tuned neurons.

PMID- 11301080
TI  - Multifocal pupillary light response fields in normal subjects and patients with
      visual field defects.
AB  - The optimal conditions for recording focal pupillary light responses with a
      multifocal stimulation technique were determined, and the technique was applied
      to normal subjects and patients with visual field defects. Thirty-seven hexagonal
      stimuli were presented on a TV monitor with a visual field of 40 degrees diameter
      under a constant background illumination. Using a slow (4.7 Hz) m-sequence,
      reliable focal responses were obtained in both normal subjects and patients. The
      pupillary field and visual field were well correlated in patients with retinal
      diseases, but the correlation was not strong in patients with optic-nerve
      diseases. Pupillary light responses were reduced in the blind hemifield in
      patients with post-geniculate lesions. These results indicate that the multifocal
      stimulation technique can be used clinically to obtain a pupillary field for
      objective visual field testing.

PMID- 11301081
TI  - Response characteristics of the normal retino-cortical pathways as determined
      with simultaneous recordings of pattern visual evoked potentials and simple motor
      reaction times.
AB  - PURPOSE: In an attempt to explain the existing discrepancies regarding the
      relationship between electrophysiological and psychophysical measurements of
      visual transmission time we compared, in humans, the response characteristics of
      the normal retino-cortical pathways with simultaneously obtained pattern visual
      evoked potentials (PVEP) and simple motor reaction times (RT). METHODS: PVEPs and
      manual RTs were recorded simultaneously using a reversing checkerboard with
      different spatial frequency and contrast combinations chosen to elicit responses
      favoring the magnocellular or parvocellular pathways. The amplitude and peak time
      of the P1 wave of the PVEP were compared to the mean RT. Other parameters of the
      RT, such as mode and standard deviation were also considered. RESULTS: The RT is
      not modified in the same fashion as the peak time of the P1 wave of the PVEP, the
      peak time of the PVEP demonstrating a spatial frequency selectivity, while the RT
      does not. Further comparative analysis of the PVEP and RT shows that the RT is
      faster for stimuli of lower contrast and spatial frequency, while the PVEP
      amplitude is larger and its peak time shorter for higher contrast and spatial
      frequency stimuli. CONCLUSIONS: Our findings suggest that PVEP and RT measures
      recruit distinct physiological characteristics and appear to be differently
      modulated while travelling along the retino-cortical pathway. Our results also
      show the importance of obtaining electrophysiological and psychophysical measures
      concomitantly to insure elimination of combined inter-stimulus and inter-session
      variability.

PMID- 11301082
TI  - On-bipolar cells and depolarising third-order neurons as the origin of the ERG-b
      wave in the RCS rat.
AB  - In the retinas of Royal College of Surgeons (RCS) rats light induces an increase
      in distal extracellular potassium irrespective of the age, between days 19-24 and
      days 29-35 postpartum, but by days 29-35 the ERG b-wave has become reduced. The
      synaptic blocker 2-amino-4-phosphonobutyric acid (APB) causes the abolition of
      both the b-wave and the potassium increase at any age. MgCl2 greatly reduces the
      b-wave at all ages and abolishes the potassium increase in older rats, but in
      younger rats the potassium increase is enlarged. Since this increase occurs in
      the absence of the b-wave it is unlikely that the on-bipolar cells are the only
      sources of the b-wave. Because the NMDA receptor blocker ketamine reduces the b
      wave, third order neurons, which possess NMDA receptors, could contribute to the
      b-wave.

PMID- 11301084
TI  - Neuroendoscopic third ventriculostomy for hydrocephalus in adults: report of a
      single unit's experience with 63 cases.
AB  - BACKGROUND: Neuroendoscopic third ventriculostomy (NTV) is becoming a first line
      treatment for hydrocephalus in this center. Its use in a consecutive series of
      adults is reported. METHOD: Initially a retrospective data collection after 7
      months becoming prospective studying all patients who underwent NTV in this
      center. The adults (17 years or older) have been studied. RESULTS: Sixty-three
      patients met the criteria for inclusion: 38 male, 25 female. Mean age at first
      NTV 37.5 years. There was an 80% success rate (i.e., no further therapy for the
      hydrocephalus required). Follow-up was for a mean of 3.1 years. The largest
      subgroup were patients with third ventricular tumours (35%), of whom 86% were
      successfully treated. Mean time to failure for the whole series was 8.5 months
      (range immediate--30 months). Complications occurred in 17.5%; those deemed
      serious in 11%. There were three deaths (4.7%) within 30 days of the procedure.
      There were six other deaths during follow-up, five because of tumour progression
      and one because of pneumonia. CONCLUSIONS: This procedure lends itself to the
      treatment of hydrocephalus in adults and appears to be more successful than in
      young children. It is efficacious in both previously shunted and non shunted
      patients. It is now the first-line treatment for noncommunicating hydrocephalus
      in this center and also for patients with shunt failure who are anatomically
      suitable, having cerebrospinal fluid spaces large enough to admit the endoscope.
      The complication and mortality rates compare favorably with those for shunts.

PMID- 11301086
TI  - Continuous intrathecal morphine treatment for chronic pain of nonmalignant
      etiology: long-term benefits and efficacy.
AB  - BACKGROUND: To analyze, prospectively, the long-term effects of continuous
      intrathecal morphine infusion therapy in 16 patients with chronic nonmalignant
      pain syndromes. METHODS: Twenty-five patients with severe, chronic, nonmalignant
      pain that had proven refractory to conservative management were considered
      candidates for trial of intrathecal spinal morphine. Sixteen patients achieved
      more than 50% pain relief after a trial period of intrathecal morphine infusion.
      They were implanted with fully implantable and programmable pumps through which
      morphine was delivered intrathecally on a continuous basis. These patients were
      followed prospectively and underwent careful evaluation of their functional and
      mental status, and pain intensity measurements using standardized techniques
      before treatment and every 6 months thereafter in the follow-up period. The
      follow-up period ranged from 13 months to 49 months (mean 29.14 months +/- 12.44
      months) for the patients who had implanted morphine pumps. RESULTS: The mean
      morphine dosage initially administered was 1.11 mg/day (range 0.2--6.5 mg/day);
      after 6 months, it was 3.1 mg/day (range 0.4--8.75 mg/day). In long-term
      observation, no patient had a constant dosage history. The patients who received
      intrathecal morphine for longer than 2 years all showed an increase in morphine
      dosage to more than 10 mg/day. The best long-term results were seen with
      deafferentation pain and mixed pain, with 75% and 61% pain reduction (visual
      analog scale), respectively. Nociceptive pain patients had best pain relief
      initially (78% pain reduction) but it tended to decrease over the follow-up
      period to 57% pain reduction at final follow-up. The average pain reduction for
      all groups after 6 months was 67.5% and at last follow-up, it was 57.5%. Ten
      patients were satisfied with the delivery system and eleven reported improvement
      in their quality of life. In two patients, morphine was not able to adequately
      control the pain without producing undesirable side effects requiring the
      addition of clonidine to their infusion medication. In this series, 12 patients
      were considered successes and 4 patients were considered failures. In two
      patients, the intrathecal opioid therapy was unable to produce satisfactory pain
      relief and in the other two patients the pumps had to be explanted because of
      intolerable side effects. CONCLUSIONS: In our experience, the administration of
      intrathecal opioid medications for nonmalignant pain is justified in carefully
      selected patients.

PMID- 11301090
TI  - Progress in the diagnosis and treatment of patients with meningiomas. Part I:
      diagnostic imaging, preoperative embolization.
AB  - BACKGROUND: The clinical management of patients with meningiomas has changed over
      the past decade. Change has occurred because of a variety of factors including
      improved diagnostic imaging, better results with surgery and interventional
      neuroradiology, and the advent of radiosurgery. Recent clinical studies from
      several disciplines have provided new information on topics germane to the
      management of patients with meningiomas. Collecting this information into a
      series of review articles would have significant value, primarily for
      neurosurgeons. OBJECTIVE: The purpose of this first paper is to bring together
      and evaluate the available data on: 1) noninvasive diagnostic imaging of
      meningiomas, including magnetic resonance imaging (MRI), computed tomography (CT)
      scanning, and MR angiography, venography and spectroscopy; 2) the present role of
      cerebral angiography in patients with meningiomas; and 3) the current status of
      preoperative embolization for these tumors. RESULTS: With the advent of MR
      technology, the quality of diagnostic imaging for meningiomas has improved
      dramatically, and this is reflected in more sophisticated preoperative planning.
      MR imaging provides improved delineation of dura and sinus involvement, and even
      information about a tumor's consistency. Meningiomas have characteristic
      neuroimaging features, yet other lesions can still mimic a meningioma. MR
      venography can be used to demonstrate sinus patency, but intra-arterial cerebral
      angiography gives the most precise information concerning the degree of tumor
      involvement of critical vascular structures, and the anatomy of arterial feeders.
      In trained hands, superselective catheterization for preoperative embolization of
      meningiomas is feasible, and seems to be reasonably safe. CONCLUSIONS: MR
      imaging, CT scans, and cerebral angiography can currently be used in a
      complementary fashion to diagnose, evaluate, and treat patients with meningiomas,
      with a high degree of clinical certainty. Angiography is used to determine the
      sites of blood supply to the tumor, which can then be attacked first
      intraoperatively, making tumor removal easier. Preoperative embolization
      continues to have value in selected patients, including those in whom the blood
      supply to the tumor is difficult to access at the time of surgery.

PMID- 11301091
TI  - Warning signs along the road.

PMID- 11301092
TI  - Single incision for implanting a vagal nerve stimulator system (VNSS): technical
      note.
AB  - BACKGROUND: A technique for implanting the vagal nerve stimulator system through
      a single incision is described. METHOD: A transverse incision is made in the
      lower part of the neck. Subcutaneous (s.c.) dissection is then done over the
      clavicle into the infraclavicular area to create a pocket. The vagus nerve is
      exposed and the electrodes are wrapped around it through the neck incision. The
      distal ends of the lead are connected to the pulse generator, and latter is then
      placed in the infraclavicular pocket through the neck incision. RESULTS: Thirty
      eight implants were conducted with this technique. The pulse generator could be
      implanted and anchored to the underlying tissue without any difficulty. Except
      for wound infections in two patients there was no other complication. CONCLUSION:
      A single incision is an alternate to the double incision procedure. This
      procedure can be performed safely.

PMID- 11301094
TI  - Acetylcholinesterase and butyrylcholinesterase histochemical activities and tumor
      cell growth in several brain tumors.
AB  - BACKGROUND: The hydrolysis enzymes of the acetylcholine, acetylcholinesterase,
      and butyrylcholinesterase are involved in non-cholinergic functions such as
      proliferation processes and cellular adhesion. These enzymes have been found in
      several tumors other from brain tumors. METHODS: Thirty fresh brain tumor
      specimens were obtained from biopsies taken during neurosurgical procedures. The
      specimens were cut in two parts, one designated for routine histopathological
      control and the other for histochemical and growth studies. The formalin fixed
      specimens were serially cut at 10 microm in a freezing cryostat, mounted in
      gelatin-coated slides, and processed for sensitive histochemical detection of
      acetylcholinesterase and butyrylcholinesterase. The other specimens were
      processed for a HMEM cell growth culture. RESULTS: The results show the
      coexistence of acetylcholinesterase and butyrylcholinesterase in all tumors
      studied. Type II and III gliomas and oligodendrogliomas show moderate activity of
      both cholinesterases, whereas in type IV glioma and meningiomas the labeling of
      both cholinesterases was high. In the craniopharyngiomas a high
      acetylcholinesterase activity was observed and low level of butyrylcholinesterase
      labeling. The cell growth was high only in the cases in which
      butyrylcholinesterase activity was high, such as type IV glioma. In type II and
      III gliomas, oligodendroglioma, and craniopharyngioma the growth rate was slow.
      CONCLUSIONS: These results could indicate a possible relationship between the
      presence of butyrylcholinesterase and acetylcholinesterase in brain tumor tissue
      and cellular proliferation in tumorigenesis.

PMID- 11301095
TI  - Sellar hemangiopericytoma mimicking pituitary adenoma.

PMID- 11301098
TI  - Re-evaluation of cellulose acetate polymer: angiographic findings and
      histological studies.
AB  - BACKGROUND: Cellulose acetate polymer (CAP) is a new liquid embolic material that
      has been used experimentally in intravascular treatment of intracranial
      aneurysms. But this compound is still controversial in some aspects such as
      safety, efficiency, and histological changes. In this study, we re-evaluated the
      material with regard to intravascular treatment of aneurysms. METHODS: The
      carotid arteries of rats and experimental aneurysms in canines were embolized
      with CAP. The effects of CAP were evaluated according to angiographic and
      histological results. RESULTS: A strong chemo-corrosive effect was observed. This
      led to severe damage to vessels and rupture of two thrombosed canine aneurysm
      models. There were significant technical difficulties including out-flow of CAP
      and a high rate of occlusion of the parent arteries. CONCLUSIONS: We conclude
      that currently CAP is not an ideal embolic material for intracranial aneurysms.
      Further tests and improvements are needed before it can be widely used
      clinically.

PMID- 11301100
TI  - Ruptured middle cerebral artery aneurysm and bilateral chronic subdural
      hematomas.
AB  - BACKGROUND: While rupture of a cerebral aneurysm into the subdural space is rare,
      aneurysmal subarachnoid hemorrhage in the presence of subdural hematoma(s) is
      much more uncommon. Such a patient requires changes in routine perioperative
      management. CASE DESCRIPTION: A patient with a ruptured middle cerebral artery
      bifurcation aneurysm and bilateral subdural hematomas is presented. He underwent
      successful aneurysm clipping and subdural hematoma evacuations. At the time of
      surgery, measures commonly used to obtain brain relaxation were avoided. The
      patient was kept normovolemic, normocarbic, and normotensive. He recovered
      completely and resumed his prior occupation. CONCLUSIONS: Changes in standard
      techniques for a patient undergoing a pterional craniotomy for a ruptured
      cerebral aneurysm are required when bilateral extra-axial mass lesions are
      present.

PMID- 11301101
TI  - Why academic health centers are failing.

PMID- 11301102
TI  - "Don't wait to become a great man--be a great boy!".

PMID- 11301104
TI  - Recent progress in the pathogenesis and management of essential thrombocythemia.
AB  - In the last decade, the diagnosis of essential thrombocythemia (ET) has been
      refined by appreciation of the occurrence of karyotypically occult but
      molecularly evident chronic myelogenous leukemia and morphologically subtle
      myelodysplastic syndrome (MDS) and cellular-phase agnogenic myeloid metaplasia
      (AMM). Although ET continues to be defined by the presence of nonreactive
      thrombocythemia that is not accounted for by another chronic myeloid disorder,
      recent studies of clonality and other laboratory parameters have suggested
      clinically relevant biologic heterogeneity among affected patients. Furthermore,
      randomized, prospective, and controlled retrospective data have provided
      additional clinical information that has resulted in the development of risk
      categories and risk-adjusted treatment recommendations.

PMID- 11301103
TI  - Therapeutic advances in the treatment of hairy cell leukemia.

PMID- 11301105
TI  - Allogenic stem cell transplantation as salvage therapy for patients relapsing
      after autologous transplantation: experience from a single institution.
AB  - The prognosis of patients relapsing after an autologous transplant (autoSCT) is
      very poor. Allogenic stem cell transplantation (alloSCT) offers the possibility
      of curing some of these patients, at the cost, however, of a high transplant
      related mortality (TRM). The aim of this study was to analyze the outcome of 14
      consecutive patients with hematologic malignancies, from a single institution,
      who underwent alloSCT for progressive disease after autoSCT. Patients had
      relapsed at a median of 11.5 months (range 2-72) after autoSCT and they underwent
      alloSCT at a median of 25.5 months (range 7-73) from the first transplant. Ten
      patients received HLA-identical related peripheral blood progenitor cells, three
      patients underwent matched-unrelated donor marrow transplants, and one patient
      received a mismatched related transplant. Conditioning regimens consisted of
      total body irradiation plus cyclophosphamide (n=5) or melphalan (n=1), or high
      dose combination chemotherapy (n=8). Cyclosporin A and methotrexate were
      administered as graft-versus-host disease (GVHD) prophylaxis. Eight patients
      (57%) developed grade II-IV acute GVHD. All evaluable patients (n=6) presented
      extensive chronic GVHD. Overall survival at 1 year was 16% (median 3.5 months,
      95% CI 0.7-10.3). Ten patients (71%) died from transplant related complications
      at a median of 3.5 months (range 0.7-11). Only one patient died of recurrent
      disease. Three patients remain alive and in complete remission at the time of
      this report (4, 20 and 20 months, respectively). In conclusion, alloSCT offers
      the possibility of a sustained control of the disease in some patients who
      relapse after an autoSCT. However, the procedure is associated with a high
      transplant-related mortality. Better results might be obtained by carefully
      selecting patients and by reducing the intensity of the preparative regimen.

PMID- 11301106
TI  - Mitochondrial disruption and limited apoptosis of erythroblasts are associated
      with high risk myelodysplasia. An ultrastructural analysis.
AB  - AIMS: To investigate the ultrastructural characteristics of erythroblasts in
      myelodysplasia (MDS) which might be of additional importance in understanding its
      pathogenesis. METHODS AND RESULTS: 22 patients were classified according to FAB
      (French-American-British classification), IPSS (international prognostic score
      system), cytogenetic risk factors and transfusion dependency. Using electron
      microscopy, in 77% of the cases, nuclear abnormalities consisting of disrupted
      membranes and cystic/dilated perinuclear spaces were noted. In a limited number
      of patients (n=7), a low percentage of apoptosis in the erythroid lineage (mean
      3.1+/-1.6%; median 3%: range 1-6) (normal controls: <0.5%) could be noted,
      primarily in mature erythroblasts and significantly associated with spongiform
      nuclear features. In all patients extensive cytoplasmic vacuolization and myelin
      figures in erythroblasts were demonstrated. In 55% of the cases, enlarged and
      abnormal mitochondria were observed, significantly associated with iron
      accumulation. A significant inverse relation existed between the absence of
      apoptosis and more advanced, or high risk disease and cytogenetic risk factors.
      Mitochondrial abnormalities were significantly correlated with high risk disease
      as well with an increase in transfusion dependency. CONCLUSIONS: These data
      indicate that in MDS apoptosis may play a role in early stages of disease. The
      overall prominent defects in mitochondria might be an additional defect that is
      involved in ineffective erythropoiesis.

PMID- 11301107
TI  - Intracellular P-gp contributes to functional drug efflux and resistance in acute
      myeloid leukaemia.
AB  - Drug compartmentalization as well as drug efflux can contribute to drug
      resistance. We demonstrate the presence of P-gp in intracellular vesicles in
      certain AML cell lines and show localization of DNR to a similar subcellular
      compartment(s) that can be altered in the presence of P-gp inhibitors. Analysis
      of leukaemic cell lines and 50 AML patient samples showed that the level of P-gp
      mRNA or total P-gp protein correlated better with drug efflux than surface P-gp
      protein, suggesting that intracellular P-gp may contribute to MDR in AML.
      Therefore, the level of total P-gp protein or mRNA may be a better indicator of
      MDR than surface P-gp protein. In addition, we provide evidence for a novel
      mechanism of drug sequestration in K562 myeloid leukaemic cells.

PMID- 11301108
TI  - ATRA, NF-kappaB and ATL.

PMID- 11301109
TI  - Minimal residual disease detection by flow cytometry: Can it serve as a predictor
      of future relapse?

PMID- 11301110
TI  - Soluble Kit receptor blocks stem cell factor bioactivity in vitro.
AB  - Stem cell factor (SCF) is a growth factor that promotes the survival,
      proliferation, and differentiation of hematopoietic cells. SCF and its receptor,
      Kit, are normally present in both cell surface and soluble forms. Both forms of
      Kit can bind SCF. However, the function of soluble Kit is unknown. In order to
      determine if soluble Kit can modulate SCF activity, we produced a fusion protein,
      Kit-Fc, comprised of the extracellular domain of murine Kit and the Fc portion of
      human IgG(1) and investigated its ability to bind 125I-SCF and to inhibit SCF
      stimulated hematopoietic colony growth in vitro. Stable cell lines expressing Kit
      Fc were generated and Kit-Fc was purified to greater than 95% purity. Scatchard
      analysis demonstrated that Kit-Fc binds iodinated SCF with high affinity (Kd 570
      pM). Kit-Fc also bound to transmembrane SCF displayed on the surface of
      fibroblasts. The murine mast cell line IC2 was engineered to express murine Kit
      on the cell surface and was demonstrated to proliferate in the presence of SCF.
      Kit-Fc completely blocked SCF-stimulated proliferation of IC2-Kit cells, but not
      IL-3-stimulated growth of IC2-Kit cells, demonstrating the specificity of Kit-Fc.
      We investigated the ability of Kit-Fc to block SCF-stimulated murine
      hematopoietic colony growth. Kit-Fc blocked SCF-stimulated erythroid colony
      growth as effectively as a neutralizing anti-Kit monoclonal antibody, ACK2, but
      did not block erythropoietin-stimulated erythroid colony growth. Likewise, Kit-Fc
      blocked SCF-stimulated myeloid colony growth as effectively as ACK2 antibody, but
      did not block IL-3- or GM-CSF-stimulated myeloid colony growth. These results
      indicate that a form of soluble Kit binds SCF with high affinity, and can
      specifically block the ability of SCF to stimulate hematopoietic colony growth,
      suggesting that one function of soluble Kit may be to modulate SCF bioactivity.

PMID- 11301114
TI  - How the Hepatitis C virus replicates.

PMID- 11301111
TI  - 8-Cl-adenosine mediated cytotoxicity and sensitization of T-lymphoblastic
      leukemia cells to TNFalpha-induced apoptosis is via inactivation of NF-kappaB.
AB  - These data show that 8-Cl-cAMP is cytotoxic to the lymphoblastic leukemia cell
      line CEM and its vinblastine selected multidrug resistant derivative, CEM/VLB100
      although PKA was not involved in these effects. The cytotoxic effects of 8-Cl
      cAMP was abrogated by cotreatment with either ADA or IBMX which indicated a
      degradation form of 8-Cl-cAMP was needed for this cytotoxicity. CEM and
      CEM/VLB100 cells displayed a notable sensitivity to 8-Cl-adenosine-induced growth
      inhibition and apoptosis. 8-Cl-adenosine increased the cytosolic levels of
      IkappaBalpha which prevented NF-kappaB nuclear translocation. 8-Cl-adenosine also
      prevented TNFalpha-induced IkB decay and NF-kappaB activation in CEM and
      CEM/VLB100 cells.

PMID- 11301115
TI  - SOral gene therapy.

PMID- 11301116
TI  - A mouse with a memory like an elephant.

PMID- 11301117
TI  - The heart of the matter.

PMID- 11301118
TI  - Fluorescent cancer detection.

PMID- 11301119
TI  - Blocking Alzheimer's [correction of Altzheimer's].

PMID- 11301120
TI  - Nano-sequencers.

PMID- 11301121
TI  - Genomics joint venture 1.

PMID- 11301122
TI  - Adenosine nerve growth factors.

PMID- 11301124
TI  - Genomics joint venture 2.

PMID- 11301123
TI  - Influenza virus replication blocked.

PMID- 11301125
TI  - Nano-electricians.

PMID- 11301126
TI  - Life is sweet for superbeads.

PMID- 11301127
TI  - Bacteriophage versus bacteria.

PMID- 11301128
TI  - The Icelandic genome debate.
AB  - Three of the central issues in contemporary debates about the commodification of
      the human body are those of property, ownership, and access. This article uses
      the case of the central medical database on Icelanders to discuss contesting
      claims about the ownership of the human genome, with respect to the rapid
      development of biotechnology, human genome projects and DNA collections. We
      emphasize the contrast between commercial and communitarian perspectives and to
      illustrate our argument we explore debates about the Icelandic database. These
      debates have been intense, focusing on a range of issues, including ethics,
      academic freedom, public health and, last but not least, the control and
      ownership of medical records, genetic information and genealogical data. This
      article should be seen primarily as an anthropological commentary on ongoing
      developments.

PMID- 11301129
TI  - Biotechnology and the utilization of biowaste as a resource for bioproduct
      development.
AB  - There is widespread concern that increasing concentrations of carbon dioxide and
      other greenhouse gases in the earth's atmosphere will ultimately lead to climate
      changes. Recognizing the important role that fossil fuels have in the economies
      and lifestyles of people throughout the world, it is reasonable to ask if the
      global economy can be powered in ways that might have less impact on the
      environment because they discharge less carbon dioxide. A way of addressing this
      sensitive issue could be through the biodevelopment of biowaste as an alternative
      and renewable energy resource. Landfilling and incineration are popular ways to
      deal with biowaste but both cause negative environmental effects such as the use
      of valuable land and production of dangerous gases. The structural components of
      cells, cellulose and hemicellulose, make biowaste very susceptible for bioproduct
      development and biowaste offers biotechnology an opportunity to assist in
      maintaining environmental quality.

PMID- 11301130
TI  - The human proteomics initiative (HPI).
AB  - The availability of the human genome sequence has enabled the exploration and
      exploitation of the human genome and proteome to begin. Research has now focussed
      on the annotation of the genome and in particular of the proteome. With expert
      annotation extracted from the literature by biologists as the foundation, it has
      been possible to expand into the areas of data mining and automatic annotation.
      With further development and integration of pattern recognition methods and the
      application of alignments clustering, proteome analysis can now be provided in a
      meaningful way. These various approaches have been integrated to attach, extract
      and combine as much relevant information as possible to the proteome. This
      resource should be valuable to users from both research and industry.

PMID- 11301131
TI  - Antibacterial vaccine design using genomics and proteomics.
AB  - After 200 years of practice, vaccinology has proved to be very effective in
      preventing infectious diseases. However, several human and animal pathogens exist
      for which vaccines have not yet been discovered. As for other fields of medical
      sciences, it is expected that vaccinology will greatly benefit from the emerging
      genomics technologies such as bioinformatics, proteomics and DNA microarrays. In
      this article the potential of these technologies applied to bacterial pathogens
      is analyzed, taking into account the few existing examples of their application
      in vaccine discovery.

PMID- 11301132
TI  - Basic microarray analysis: grouping and feature reduction.
AB  - DNA microarray technologies are useful for addressing a broad range of biological
      problems - including the measurement of mRNA expression levels in target cells.
      These studies typically produce large data sets that contain measurements on
      thousands of genes under hundreds of conditions. There is a critical need to
      summarize this data and to pick out the important details. The most common
      activities, therefore, are to group together microarray data and to reduce the
      number of features. Both of these activities can be done using only the raw
      microarray data (unsupervised methods) or using external information that
      provides labels for the microarray data (supervised methods). We briefly review
      supervised and unsupervised methods for grouping and reducing data in the context
      of a publicly available suite of tools called CLEAVER, and illustrate their
      application on a representative data set collected to study lymphoma.

PMID- 11301133
TI  - Decision making under the Cartagena Protocol on Biosafety.

PMID- 11301137
TI  - How strong is natural selection?
AB  - The strength of selection in nature has long been a controversial subject, partly
      because there were few quantitative measurements of phenotypic selection
      available until recently. In a new paper, Kingsolver and colleagues reviewed 63
      studies and found that the median standardized directional selection gradient (a
      measure of the strength of phenotypic selection) was 0.16. Whether this means
      selection in nature is strong or weak depends both on one's point of view and on
      the error in selection estimates.

PMID- 11301138
TI  - Paving the way to the future of Amazonia.
AB  - The fate of the Brazilian Amazon is threatened by a new wave of frontier
      expansion following new infrastructure commitments worth US$40 bn from the
      federal Government. In a recent paper, alarming rates of deforestation and forest
      degradation have been predicted, which could be either pessimistic or optimistic
      depending on the scale of forest disturbance being considered. A more decisive
      preventative approach is needed to prevent further impoverishment of both the
      biota and rural population of Amazonia.

PMID- 11301140
TI  - Vicious fig wasps in viscous populations.

PMID- 11301139
TI  - The use and abuse of population viability analysis.
AB  - A recent study by Brook et al. empirically tested the performance of population
      viability analysis (PVA) using data from 21 populations across a wide range of
      species. The study concluded that PVAs are good at predicting the future dynamics
      of populations. We suggest that this conclusion is a result of a bias in the
      studies that Brook et al. included in their analyses. We present arguments that
      PVAs can only be accurate at predicting extinction probabilities if data are
      extensive and reliable, and if the distribution of vital rates between
      individuals and years can be assumed stationary in the future, or if any changes
      can be accurately predicted. In particular, we note that although catastrophes
      are likely to have precipitated many extinctions, estimates of the probability of
      catastrophes are unreliable.

PMID- 11301141
TI  - Faecal pellets and energy flow in rivers.

PMID- 11301142
TI  - Inbreeding in nature: brothers and sisters, do not unite!

PMID- 11301143
TI  - Landscape dynamics can accelerate metapopulation extinction.

PMID- 11301145
TI  - The first ever global ecosystem assessment.

PMID- 11301144
TI  - MPAs receive strong endorsement.

PMID- 11301146
TI  - Is science saving endangered species?

PMID- 11301147
TI  - Ecoinformatics: facilitating access to existing data sets.

PMID- 11301148
TI  - Blue-ribbon panel examines salmon conservation.

PMID- 11301149
TI  - Assessing viability of forest species.

PMID- 11301150
TI  - Entire encyclopedia devoted to biodiversity.

PMID- 11301151
TI  - An invitation to ecological economics.
AB  - The emerging interdisciplinary field of ecological economics should be a
      recognized research priority. Only through a combination of sound ecology and
      good economics can we hope to manage our exploitation of the biosphere in a
      manner that is both sustainable and efficient. This article is an invitation to
      ecologists to use economic tools and to participate in ecological economic
      debate. To this end, we review basic ecological economic concepts and discuss how
      the field has arisen, what benefits it offers, and what challenges it must
      overcome.

PMID- 11301152
TI  - Genome sequences and evolutionary biology, a two-way interaction.
AB  - Complete genome sequences are accumulating rapidly, culminating with the
      announcement of the human genome sequence in February 2001. In addition to
      cataloguing the diversity of genes and other sequences, genome sequences will
      provide the first detailed and complete data on gene families and genome
      organization, including data on evolutionary changes. Reciprocally, evolutionary
      biology will make important contributions to the efforts to understand functions
      of genes and other sequences in genomes. Large-scale, detailed and unbiased
      comparisons between species will illuminate the evolution of genes and genomes,
      and population genetics methods will enable detection of functionally important
      genes or sequences, including sequences that have been involved in adaptive
      changes.

PMID- 11301153
TI  - Design of reserve networks and the persistence of biodiversity.
AB  - Sophisticated computational methods have been developed to help us to identify
      sets of nature reserves that maximize the representation of regional diversity,
      but, until recently, the methods have not dealt explicitly and directly with the
      main goal of reserve networks, that of the long-term maintenance of biodiversity.
      Furthermore, the successful application of current methods requires reliable
      information about species distributions, which is not always available. Recent
      results show that data quality, as well as the choice of surrogates for
      biodiversity, could be critical for successful reserve design. Because of these
      problems and a lack of communication between scientists and managers, the impact
      of computational site-selection tools in applied conservation planning has been
      minimal.

PMID- 11301154
TI  - Linking plants to rocks: ectomycorrhizal fungi mobilize nutrients from minerals.
AB  - Plant nutrients, with the exception of nitrogen, are ultimately derived from
      weathering of primary minerals. Traditional theories about the role of
      ectomycorrhizal fungi in plant nutrition have emphasized quantitative effects on
      uptake and transport of dissolved nutrients. Qualitative effects of the symbiosis
      on the ability of plants to access organic nitrogen and phosphorus sources have
      also become increasingly apparent. Recent research suggests that ectomycorrhizal
      fungi mobilize other essential plant nutrients directly from minerals through
      excretion of organic acids. This enables ectomycorrhizal plants to utilize
      essential nutrients from insoluble mineral sources and affects nutrient cycling
      in forest systems.

PMID- 11301156
TI  - Policy making within ecological uncertainty: lessons from badgers and GM crops.

PMID- 11301155
TI  - Compensation for a bad start: grow now, pay later?
AB  - Nutritional conditions during key periods of development, when the architecture
      and modus operandi of the body become established, are of profound importance in
      determining the subsequent life-history trajectory of an organism. If developing
      individuals experience a period of nutritional deficit, they can subsequently
      show accelerated growth should conditions improve, apparently compensating for
      the initial setback. However, recent research suggests that, although
      compensatory growth can bring quick benefits, it is also associated with a
      surprising variety of costs that are often not evident until much later in adult
      life. Clearly, the nature of these costs, the timescale over which they are
      incurred and the mechanisms underlying them will play a crucial role in
      determining compensatory strategies. Nonetheless, such effects remain poorly
      understood and largely neglected by ecologists and evolutionary biologists.

PMID- 11301157
TI  - Light after dark: the partnership for enhancing expertise in taxonomy.

PMID- 11301159
TI  - Uterine electrical activity as predictor of preterm birth in women with preterm
      contractions.
AB  - OBJECTIVE: To estimate the risk of preterm birth in women admitted to the
      tertiary maternity hospital for preterm contractions by measuring electrical
      uterine activity. STUDY DESIGN: The study included 47 patients with contractions
      between the 25th and 35th week of gestation and additional risk factors for
      preterm delivery. Uterine electrical activity was recorded using bipolar
      electrodes placed on the abdominal surface. A logistic model with the
      electromyographic and obstetric data was built, preterm delivery before 37th week
      of gestation being the outcome measure. RESULTS: Seventeen patients (36%)
      delivered before term. Logistic regression model suggested only the intensity of
      electrical uterine activity and woman's body weight to be significant predictors
      of preterm delivery, with high values related to preterm birth. They predict
      preterm delivery with the sensitivity of 47% and specificity of 90%. CONCLUSION:
      We propose uterine EMG as a simple, non-invasive means to estimate the risk of
      preterm birth in a high-risk population with multiple risk factors present.

PMID- 11301158
TI  - Non-synaptic ion channels in insects--basic properties of currents and their
      modulation in neurons and skeletal muscles.
AB  - Insects are favoured objects for studying information processing in restricted
      neuronal networks, e.g. motor pattern generation or sensory perception. The
      analysis of the underlying processes requires knowledge of the electrical
      properties of the cells involved. These properties are determined by the
      expression pattern of ionic channels and by the regulation of their function,
      e.g. by neuromodulators. We here review the presently available knowledge on
      insect non-synaptic ion channels and ionic currents in neurons and skeletal
      muscles. The first part of this article covers genetic and structural
      informations, the localization of channels, their electrophysiological and
      pharmacological properties, and known effects of second messengers and modulators
      such as neuropeptides or biogenic amines. In a second part we describe in detail
      modulation of ionic currents in three particularly well investigated
      preparations, i.e. Drosophila photoreceptor, cockroach DUM (dorsal unpaired
      median) neuron and locust jumping muscle. Ion channel structures are almost
      exclusively known for the fruitfly Drosophila, and most of the information on
      their function has also been obtained in this animal, mainly based on mutational
      analysis and investigation of heterologously expressed channels. Now the entire
      genome of Drosophila has been sequenced, it seems almost completely known which
      types of channel genes--and how many of them--exist in this animal. There is much
      knowledge of the various types of channels formed by 6-transmembrane--spanning
      segments (6TM channels) including those where four 6TM domains are joined within
      one large protein (e.g. classical Na+ channel). In comparison, two TM channels
      and 4TM (or tandem) channels so far have hardly been explored. There are,
      however, various well characterized ionic conductances, e.g. for Ca2+, Cl- or K+,
      in other insect preparations for which the channels are not yet known. In some of
      the larger insects, i.e. bee, cockroach, locust and moth, rather detailed
      information has been established on the role of ionic currents in certain
      physiological or behavioural contexts. On the whole, however, knowledge of non
      synaptic ion channels in such insects is still fragmentary. Modulation of ion
      currents usually involves activation of more or less elaborate signal
      transduction cascades. The three detailed examples for modulation presented in
      the second part indicate, amongst other things, that one type of modulator
      usually leads to concerted changes of several ion currents and that the effects
      of different modulators in one type of cell may overlap. Modulators participate
      in the adaptive changes of the various cells responsible for different
      physiological or behavioural states. Further study of their effects on the single
      cell level should help to understand how small sets of cells cooperate in order
      to produce the appropriate output.

PMID- 11301160
TI  - Predicting preterm delivery: comparison of cervicovaginal interleukin (IL)-1beta,
      IL-6 and IL-8 with fetal fibronectin and cervical dilatation.
AB  - OBJECTIVE: To compare the cervicovaginal cytokines IL-1beta, IL-6 and IL-8 with
      fetal fibronectin (fFN) and cervical dilatation in the prediction of preterm
      delivery. STUDY DESIGN: Cervicovaginal cytokine concentration and fFN status were
      measured in 104 women with symptoms of preterm labour and intact membranes
      between 24(0) and 33(6) weeks and related to delivery within 2 and 7 days.
      RESULTS: A group of 18% had cervical dilatation > or = 1cm and 18% were positive
      for fFN. Preterm delivery within 2 and 7 days occurred in 5 and 12%,
      respectively. Only IL-6 demonstrated any ability to predict delivery within 2 and
      7 days (area under the ROC curve = 0.63 and 0.75, respectively). Using 35pg/ml
      (75th centile) as a cut-off, IL-6 had a sensitivity and specificity of 60 and 77%
      for predicting delivery within 2 days, and 62 and 80% for predicting delivery
      within 7 days. This is similar to the performance of cervical dilatation or fFN
      status. CONCLUSIONS: Measurement of cervicovaginal cytokines has limited ability
      to predict imminent delivery apart from cervicovaginal IL-6 concentrations,
      which, in this population, is equivalent to that of fFN status and cervical
      dilatation > or = 1cm.

PMID- 11301161
TI  - Effect of reactive oxygen species on fetal lung maturation.
AB  - OBJECTIVES: Fetal lung maturation in preterm infants with chorioamnionitis is
      known to be accelerated. However, the molecular basis of this pathological
      acceleration has not been elucidated. We investigated whether reactive oxygen
      species play a role in the acceleration of fetal lung maturation. STUDY DESIGN:
      On the 16th day of gestation, xanthine (1mM) and xanthine oxidase solution (0.1
      100mU/ml) were injected into the intrauterine cavity of pregnant rats. On the
      19th day of gestation, we examined the expression of the mRNA of surfactant
      associated proteins A, B and C (sp-A, sp-B and sp-C) by reverse transcription
      polymerase chain reaction. RESULTS: sp-A, sp-B and sp-C mRNAs were observed in
      lung tissue from fetal rats stimulated by xanthine-xanthine oxidase in contrast
      to the control. CONCLUSION: Reactive oxygen species in amniotic fluid might be an
      important factor in accelerated fetal lung maturation associated with
      chorioamnionitis in the rat experimental model.

PMID- 11301162
TI  - Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in amniotic fluid
      and blood plasma: implications for the mechanism of amniotic fluid embolism.
AB  - Tissue factor (TF) is known to be present in a high concentration in amniotic
      fluid. The main question of this study is whether tissue factor pathway inhibitor
      (TFPI), a natural inhibitor of TF, is present in amniotic fluid. The study group
      consisted of 28 women with normal pregnancy course, and at the first stage of
      termed labour. Fifteen non-pregnant women were the control group. TF and TFPI
      were studied by an immunoenzymatic method (ELISA). The level of TFPI in amniotic
      fluid was 38.7% of that in blood plasma (16.81+/-5.34ng/ml versus 43.41+/
      18.70ng/ml, P<0.001), while the level of TF in amniotic fluid was 44.8 times
      higher than in blood plasma (9995.93+/-8533.11pg/ml versus 252.66+/-28.84pg/ml,
      P<0.001). CONCLUSIONS: (i) It was found, for the first time, that amniotic fluid
      contains TFPI (ii) It is reasonable to assume that the intrusion of amniotic
      fluid into the blood-stream may influence the plasmatic TFPI-TF equilibrium
      resulting in intravascular blood coagulation.

PMID- 11301163
TI  - Regulation of matrix metalloproteinases and their inhibitors in uterine
      endometrial cells of patients with and without endometriosis.
AB  - OBJECTIVE: To determine whether alterations in the secretion and regulation of
      matrix metalloproteinases (MMPs) and their inhibitors are present in uterine
      endometrial cells from endometriosis patients. STUDY DESIGN: In an in vitro
      study, uterine endometrial cells from 19 regularly cycling women with and 32
      without endometriosis were treated with diethyl stilbestrol, promegestone
      (R5020), interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha). Culture
      supernatants were assayed for MMPs 1, 2, 3, and 9, and for tissue inhibitors of
      MMP (TIMP-1 and TIMP-2) by ELISA. RESULTS: MMP-3 was secreted in high
      concentrations, moderate concentrations were seen for MMP-1 and MMP-2, and very
      low concentrations for MMP-9. Substantially more TIMP-1 than TIMP-2 was secreted.
      MMP-1 and MMP-3 were uniformly attenuated by R5020, while MMP-2 was not
      influenced by hormone treatment. MMP-3 was upregulated by TNF-alpha in all
      samples while IL-1 only increased secretion in cells from endometriosis patients.
      CONCLUSION: The upregulation of MMP-3 by IL-1 may contribute to an increased
      invasiveness of uterine endometrial fragments in endometriosis patients.

PMID- 11301164
TI  - Treatment of CIN after menopause.
AB  - OBJECTIVES: To characterise cervical neoplasia after the menopause. MATERIAL AND
      METHODS: We studied our computerized files of CIN from 1993-1999. Of the 738
      cases, 78 were after menopause (11%). RESULTS: We made a report of the
      specificities of cytological and colposcopical diagnosis and the treatment given.
      Cytological results are the same after and before menopause. On the other hand,
      colposcopical patterns are significantly different because of a particular
      topography of the lesion. The majority of CIN after menopause are localized in
      the canal and are 44% versus 12. Incomplete conization is no more frequent after
      menopause than before. However, stenosis is higher: 73% unseen junction against
      15%. Therefore, at this age, a total hysterectomy could possibly be preferable.
      In this study, we will outline the positive and the negative aspects of this form
      of treatment.

PMID- 11301165
TI  - Recurrent myotonic crisis in a pregnant woman with myotonic dystrophy.

PMID- 11301166
TI  - An intracranial tumour--an uncommon cause of hyperemesis in pregnancy.
AB  - Brain tumours in pregnancy are rare. In this case vomiting and headache were the
      only signs. An assessment of the patient with vomiting in pregnancy to help reach
      a diagnosis when faced with vomiting in pregnancy is given. Following the
      diagnosis of a brain tumour during pregnancy, management should be tailored to
      the individual patient.

PMID- 11301167
TI  - Severe congenital cytomegalovirus infection with fetal hydrops in a
      cytomegalovirus-seropositive healthy woman.
AB  - We report the case of a woman whose two consecutive pregnancies resulted in
      intrauterine fetal death due to severe congenital cytomegalovirus infection. In
      both pregnancies, congenital cytomegalovirus infection was prenatally diagnosed
      on the basis of detection of cytomegalovirus DNA and specific IgM in cord blood.
      This case suggests that severe congenital cytomegalovirus infection can occur
      even in seropositive healthy women.

PMID- 11301169
TI  - Genetic aspects of venous thrombosis.

PMID- 11301171
TI  - The endothelium: vascular control of haemostasis.
AB  - Within many general functions the endothelium is equipped with a number of
      mechanisms that prevent thrombus formation in the circulatory system. It harbours
      factors that interrupt the coagulation cascade, such as antithrombin III, the
      protein C receptor thrombomodulin, and tissue factor pathway inhibitor. It
      prevents platelet activation by the production of nitric oxide and prostacyclin,
      exonucleotidases and surface heparan sulphates. Furthermore, it can trigger and
      control fibrinolysis by the synthesis and release of tissue-type plasminogen
      activator and its inhibitor PAI-1. The general properties of the endothelium are
      subject to adaptation by environmental factors, such as inflammatory mediators
      and shear forces. Interleukin-1 and tumour necrosis factor-alpha reduce the
      antithrombotic properties of the endothelium. Furthermore, local variation exists
      between different vascular beds and vessel types, such as in the endometrium.
      While the endothelium controls blood fluidity on its apical side, adaptation of
      the endothelium also prepares its involvement in tissue repair upon inflammation
      or damage. The fibrin matrix, which is formed after damage of the vascular
      system, not only acts as a sealing of the wound, but also facilitates the repair
      process by providing a scaffolding for cell invasion and angiogenesis.

PMID- 11301170
TI  - Oral contraceptives, thrombosis and haemostasis.
AB  - The use of oral contraceptives is a well-established acquired risk factor for
      venous thrombosis. In 1995, a number of epidemiological studies were published
      which suggested that women who use third generation oral contraceptives that
      contain desogestrel or gestodene as progestagen are exposed to a two- to
      threefold higher risk for venous thrombosis than women using second generation
      oral contraceptives which contain levonorgestrel. In this paper, the effects of
      oral contraceptives on the haemostatic system are discussed. It appears that
      plasma from oral contraceptive users is resistant to the anticoagulant action of
      activated protein C (APC). This phenomenon, called acquired APC resistance, is
      more pronounced in users of desogestrel or gestodene-containing oral
      contraceptives than in women who use oral contraceptive pills with
      levonorgestrel. On the basis of these observations, it was proposed that acquired
      APC resistance may be the mechanistic basis of the increased risk for venous
      thrombosis during oral contraceptive use and for the further increased thrombotic
      risk of third generation oral contraceptive users. Furthermore, the results of a
      recent cross-over study are discussed. This study indicated that a large number
      of other haemostatic parameters were changed during oral contraceptive use. Some
      of these changes were more pronounced on desogestrel-containing oral
      contraceptives. The cross-over study also showed that the increased fibrinolytic
      activity during OC use is counterbalanced by an enhanced activity of thrombin
      activatable fibrinolysis inhibitor (TAFI), a protein that participates in the
      inhibition of fibrinolysis.

PMID- 11301172
TI  - Thrombophilia and fetal growth restriction.

PMID- 11301173
TI  - Clotting disorders and placental abruption: homocysteine--a new risk factor.
AB  - Placental abruption is due to the rupture of the uterine spiral artery. The
      placenta separates totally or partially from the uterine wall during pregnancy.
      This serious syndrome has a great risk for the mother (shock and disseminated
      intravascular coagulation) and her child (mortality or morbidity). To the known
      risk factors like hypertension, the use of cocaine and smoking, homocysteine is
      recognized as an independent risk factor for vascular disease and endothelial
      dysfunction. In contrast to normal pregnancy where the spiral artery endothelium
      is replaced by trophoblast, the endothelium persists in case of placental
      abruption. In 165 women with placental vasculopathy and 139 matched controls
      hyperhomocysteinemia resulted in an odds ratio of 4.7 (95% CI: 1.6-14.0). The
      C677T mutation gave a risk of 2.5 (95% CI: 1.0-6.0). Even up to 2 or 3 years post
      partum evidence could be found of endothelial dysfunction. The combination of
      hyperhomocysteinemia and thrombotic factors like APC resistance, Protein-C,
      Protein-S, antithrombin and factor V Leiden increases the risk of placental
      abruption 3-7 times. The common denominator of the effect of homocysteine on
      blood vessels could be sited in the process of proliferation of cells that need
      proper methyl groups for proper function (DNA synthesis and expression). These
      methyl groups are delivered by D-adenosylmethionine formed from methionine after
      remethylation of homocysteine. The coagulation factors and plasma homocysteine
      values can be modulated by vitamins, folic acid and folates in particular. To
      prove the clinical value of folate supplementation placebo-randomized trials are
      urgently needed: for placebo to be started after the period of neural tube
      closure.

PMID- 11301174
TI  - Pre-eclampsia and the inflammatory response.

PMID- 11301175
TI  - Non-pregnant circulatory volume status predicts subsequent pregnancy outcome in
      normotensive thrombophilic formerly preeclamptic women.
AB  - BACKGROUND: Preeclampsia seems to be superimposed upon a preexisting hemodynamic,
      hemostatic, autoimmune or metabolic disorder. We tested the hypothesis that in
      normotensive thrombophilic formerly preeclamptic subjects, the non-pregnant
      circulatory volume status predicts the development of subsequent hypertensive
      pregnancy and/or fetal growth restriction. METHODS: In 250 non-diabetic formerly
      preeclamptic women and 15 normal parous controls, we measured and calculated the
      following variables at least 5 months postpartum at day 5 (+/-2) of the menstrual
      cycle: mean arterial pressure, body mass index, plasma volume and the clotting
      function. In the subsequent pregnancy we determined, birth weight, birth-weight
      centile and the incidence of preterm birth, fetal growth restriction, pregnancy
      induced hypertension, preeclampsia and HELLP-syndrome. We only included in the
      final analysis normotensive subjects with a thrombophilic phenotype at the time
      of the pre-pregnant screening, who had a subsequent singleton pregnancy, ongoing
      beyond 16 weeks gestation within 1 year after pre-pregnant evaluation. As a
      consequence, 23 formerly preeclamptic women and 12 controls were eligible for
      final analysis. The thrombophilic formerly preeclamptic participants received
      aspirin in combination with low-molecular-weight heparin throughout pregnancy. If
      thrombophilia was diagnosed on the basis of hyperhomocysteinemia, the treatment
      consisted of aspirin, pyridoxine and folic acid, instead. RESULTS: Among 250
      formerly preeclamptic 131/250 (52%) had a normotensive thrombophilic phenotype.
      Only 23 (18%) of these 131 participants had an ongoing pregnancy within 1 year.
      They were allocated to subgroup THROMB. None of the controls had hypertension or
      thrombophilia. In contrast, 12/15 (80%) controls had an ongoing pregnancy within
      a year. The observations in the THROMB subgroup were compared with those in the
      control group. None of the baseline demographic and blood pressure variables
      differed between THROMB and controls. With respect to pregnancy outcome, the
      incidence of the following pregnancy complications were observed in THROMB
      subjects: preterm birth: 9%, pregnancy-induced hypertension: 44%, preeclampsia:
      13%, HELLP-syndrome: 13%, and fetal growth restriction: 30%. A low non-pregnant
      plasma volume was found to predispose for hypertensive complications in a
      subsequent pregnancy. CONCLUSION: Pre-pregnant plasma volume in normotensive
      thrombophilic formerly preeclamptic women have predictive value with respect to
      hypertensive complications in the subsequent pregnancy.

PMID- 11301176
TI  - Activated protein C resistance during in vitro fertilization treatment.
AB  - Acquired resistance to the anticoagulant action of activated protein C (APC) has
      been proposed to explain the increased risk of venous thrombosis associated with
      pregnancy, hormone replacement therapy and the use of oral contraceptives. In
      this study, we have investigated whether the hormonal changes induced during in
      vitro fertilization (IVF) treatment are also associated with acquired APC
      resistance. Twenty-nine women, who were planned for an IVF cycle, donated blood
      at four time points during treatment, i.e. at baseline, down-regulation,
      hyperstimulation and luteal support. In the plasma samples, APC sensitivity
      ratios (APCsr) and the levels of progesterone and estradiol were measured. The
      changes in plasma concentrations of hormones were in accordance with literature.
      The APCsr increased significantly during hyperstimulation and remained high
      during luteal support. The extent of APC resistance occurring during IVF
      treatment was comparable to that observed during the use of second generation OC
      and was less pronounced than that occurring during pregnancy. The change in
      estradiol between baseline and hyperstimulation correlated with the change in
      APCsr. Although this suggests that plasma estrogen levels are an important
      determinant for acquired APC resistance, it remains to be established which
      plasma proteins are responsible for estrogen-induced APC resistance.

PMID- 11301177
TI  - The effect of factor V Leiden, oral contraceptive use, type of oral
      contraceptives and pregnancy on APC-r levels in women with or without a history
      of pre-eclampsia.

PMID- 11301178
TI  - Hyperhomocysteinaemia: a risk factor for preeclampsia?
AB  - Preeclampsia represents one of the most frequent complications of pregnancy,
      however, little is known about its aetiology. Damage of the endothelial layer
      lining the blood vessel wall is thought to play an important role in the
      pathophysiology of preeclampsia, accordingly, mild hyperhomocysteinaemia has been
      reported to be more prevalent among preeclamptic women. Therefore, we
      investigated the role of hyperhomocysteinaemia in preeclampsia by measuring
      plasma levels of homocysteine and studying the prevalence of the 677(C-->T)
      polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which
      may lead to reduced MTHFR enzyme activity and subsequently to higher plasma
      homocysteine levels. Plasma samples of 10 healthy non-pregnant women, 10
      normotensive pregnant women, and 20 women with preeclampsia were analysed for
      total homocysteine levels by high performance liquid chromatography. Furthermore,
      167 Dutch non-pregnant women previously hospitalised for preeclampsia and 403
      population-based controls were analysed for the 677(C-->T) polymorphism by
      polymerase chain reaction followed by restriction fragment length polymorphism
      analysis (PCR/RFLP). In normotensive pregnancy homocysteine levels were lower
      compared with levels in healthy non-pregnant controls (8.4 versus 13.7micromol/l,
      P<0.001). Women with preeclampsia showed higher concentrations than women during
      normotensive pregnancy (13.3 versus 8.4micromol/l, P<0.02). However, levels of
      homocysteine in preeclampsia were comparable to those found in healthy non
      pregnant women. PCR/RFLP showed no significant difference in the incidence of the
      677(C-->T) polymorphism in the MTHFR gene between preeclamptic women with or
      without HELLP syndrome and controls (13 and 9% homozygous for the less common T
      allele, respectively; OR 1.5, 95% CI 0.8-2.6, P=0.17). In contrast with previous
      reports, we cannot confirm that mild hyperhomocysteinaemia is a risk factor for
      preeclampsia. Pregnancy induced hyperhomocysteinaemia found in preeclampsia might
      better be explained by fluctuations in plasma volume than by the presence of the
      677(C-->T) polymorphism in the MTHFR gene.

PMID- 11301179
TI  - The distribution of PIG-A gene abnormalities in paroxysmal nocturnal
      hemoglobinuria granulocytes and cultured erythroblasts.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia that is
      characterized by a deficiency of glycosylphosphatidylinositol-anchored membrane
      proteins due to phosphatidylinositol glycan-class A (PIG-A) gene abnormalities in
      various lineages of peripheral blood cells and hematopoietic precursors. The
      purpose of our study was to clarify the distribution of PIG-A gene abnormalities
      among various cell lineages during differentiation and maturation in PNH
      patients. The expression of CD16b or CD59 in peripheral blood granulocytes or
      cultured erythroblasts from three Japanese PNH patients was analyzed using flow
      cytometry. PIG-A gene abnormalities in both cell types, including glycophorin
      A(+) bone marrow erythroblasts, were examined using nucleotide sequence analysis.
      The expression study of PIG-A genes from each patient was also performed using JY
      5 cells.Flow cytometry revealed that the erythroblasts consisted of negative,
      intermediate, and positive populations in Cases 1 and 3 and negative and
      intermediate populations in Case 2. The granulocytes consisted of negative and
      positive populations in all three cases. DNA sequence analysis indicated that all
      the PNH cases had two or three types of PIG-A gene abnormalities, and that a
      predominant clone with an abnormal PIG-A gene was different in granulocytes and
      erythroblasts from Cases 2 and 3. Expression studies showed that all the
      mutations from the patients were responsible for the null phenotype.PIG-A gene
      abnormalities result in deficiencies of glycosylphosphatidylinositol-anchored
      proteins in PNH erythroblasts and granulocytes. The distribution of predominant
      PNH clones with PIG-A gene abnormalities is often heterogeneous between the cell
      types, suggesting that a clonal selection of PIG-A gene abnormalities occurs
      independently among various cell lineages during differentiation and maturation.

PMID- 11301180
TI  - T-cell apoptosis induced by granulocyte colony-stimulating factor is associated
      with retinoblastoma protein phosphorylation and reduced expression of cyclin
      dependent kinase inhibitors.
AB  - Peripheral blood progenitor cells (PBPC) mobilized by granulocyte colony
      stimulating factor (G-CSF) promptly engraft allogeneic recipients after
      myeloablative chemotherapy for hematologic malignancies. Surprisingly, no
      exacerbation of acute graft-vs-host disease has been observed despite a 10-fold
      higher T-cell content in PBPC compared with bone marrow allografts. Because G-CSF
      can suppress T-cell proliferation in response to mitogens and enhance their
      activation-induced apoptosis, we examined the molecular mechanisms underlying G
      CSF-induced immune dysfunction. Normal allogeneic lymphocytes were challenged
      with phytohemagglutinin in the presence of serum collected after G-CSF
      administration (postG) to healthy PBPC donors, and the expression of key
      components of the cell cycle and apoptotic machineries was investigated by flow
      cytometry and Western blotting. Lymphocyte stimulation was associated with
      collapse of mitochondrial transmembrane potential, hypergeneration of reactive
      oxygen intermediates, and activation of caspase-3 and DNA fragmentation.
      Lymphocytes were arrested in a G(1)-like phase of the cell cycle, as measured by
      G(1)-phase cyclin expression and bromodeoxyuridine (BrdUrd) incorporation. Cell
      tracking experiments confirmed the occurrence of a lower number of population
      doublings in postG compared with preG cultures. Unexpectedly, the phosphorylation
      state of the protein encoded by the retinoblastoma susceptibility gene (pRB) was
      unaltered in postG cultures, and the inhibition of cell cycle progression
      occurred without the recruitment of the cyclin-dependent kinase inhibitors
      p15(INK4B), p16(INK4A), and p27(Kip1). We eventually evaluated the ability of
      antioxidant/cytoprotectant agents to prevent the G-CSF-induced mitochondrial
      dysfunction and inhibition of cell cycle progression. Of interest, both N
      acetylcysteine and amifostine reduced apoptotic cell death by 45% on average,
      inhibited the activation/processing of caspase-3, and increased BrdUrd
      incorporation in postG cultures. Based on these experimental findings, a model is
      proposed in which T-cell activation in the presence of serum immunoregulatory
      factor(s) induced by G-CSF is associated with a molecular phenotype mimicking the
      G(1)-S transition and consisting of pRB phosphorylation, lack of CDKI
      recruitment, and reduced cyclin-E expression. The putative relationship between
      lymphocyte mitogenic unresponsiveness and apoptosis induction would occur at the
      level of key molecules shared by the cell cycle and apoptotic machineries.
      Whether the G-CSF-mediated modulation of lymphocyte functions in vitro is
      beneficial in transplantation medicine remains to be determined.

PMID- 11301181
TI  - Bivalent binding and signaling characteristics of Leridistim, a novel chimeric
      dual agonist of interleukin-3 and granulocyte colony-stimulating factor
      receptors.
AB  - Leridistim is a member of a novel family of engineered chimeric cytokines,
      myelopoietins, that contain agonists of both interleukin-3 (IL-3) receptors (IL
      3R) and granulocyte colony-stimulating factor (G-CSF) receptors (G-CSFR). To more
      clearly understand Leridistim's function at the molecular level, binding to both
      IL-3R and G-CSFR and subsequent signaling characteristics have been delineated.
      The affinity of Leridistim for the human G-CSFR was found to be comparable to
      that of native G-CSF (IC(50) = 0.96 nM and 1.0 nM, respectively). Both Leridistim
      and G-CSF induced receptor tyrosine phosphorylation to a similar maximal level.
      Compared with native recombinant human IL-3 (rhIL-3), Leridistim was found to
      possess higher affinity for the IL-3R alpha chain (IL-3Ralpha) (IC(50) = 85 nM
      and 162 nM, respectively). However, the increase in Leridistim binding affinity
      to the functional, high-affinity heterodimeric IL-3Ralphabeta(c) receptor is
      lower than that observed with rhIL-3 (85 nM and 14 nM vs 162 nM and 3.5 nM,
      respectively). Leridistim induced tyrosine phosphorylation of beta(c) to a level
      comparable to native IL-3, and the level of JAK2 tyrosine phosphorylation in
      cells expressing both IL-3R and G-CSFR was comparable to that observed with IL-3
      or G-CSF alone. The ability of Leridistim to interact with IL-3R and G-CSFR
      simultaneously was demonstrated using surface plasmon resonance analysis. These
      studies were extended to demonstrate that Leridistim exhibited a higher affinity
      for the IL-3R on cells that express both the IL-3Ralphabeta(c) and the G-CSFR
      (IC(50) = 2 nM) compared with cells that contain the IL-3Ralphabeta(c) alone
      (IC(50) = 14 nM). Leridistim binds to both IL-3R and G-CSFR simultaneously and
      has been shown to activate both receptors. The bivalent avidity may explain the
      unique biologic effects and unexpected potency of Leridistim in hematopoietic
      cells compared with rhIL-3 or G-CSF alone or in combination.

PMID- 11301182
TI  - Receptor-based model accounts for phlebotomy-induced changes in erythropoietin
      pharmacokinetics.
AB  - Previous clinical studies have demonstrated two distinctive pharmacokinetic
      behaviors of erythropoietin (EPO): changes in pharmacokinetics (PK) after a
      period of rhEPO treatment and nonlinear pharmacokinetics. The objective of this
      work was to study the temporal changes in EPO's PK following phlebotomy in order
      to propose possible mechanisms for this behavior. Five healthy adult sheep were
      phlebotomized on two separate occasions 4-6 weeks apart to hemoglobin levels of
      PK 3-4 g/dL. PK parameters were estimated from the concentration-time profiles
      obtained following repeated intravenous bolus PK studies using tracer doses of
      biologically active 125I-rhEPO. Based on the changes in clearances, a PK model
      was derived to provide a mechanistic receptor-based description of the observed
      phenomena. Phlebotomy resulted in a rapid increase in the EPO plasma
      concentration, which peaked at 760 +/- 430 mU/mL (mean +/- SD) at 1.8 +/- 0.65
      days, and which coincided with a transient reduction in EPO clearance from
      prephlebotomy values, i.e., from 45.6 +/- 11.2 mL/hr/kg to 24.3 +/- 9.7 mL/hr/kg.
      As plasma EPO levels returned toward baseline levels in the next few days, a
      subsequent increase in EPO clearance was noted. EPO clearance peaked at 90.2 +/-
      26.2 mL/hr/kg at 8.5 +/- 3.3 days and returned to baseline by 4-5 weeks
      postphlebotomy. The proposed model derived from these data includes positive
      feedback control of the EPO receptor (EPOR) pool. The model predicts that: 1) the
      initial reduction in EPO plasma clearance is due to a transient saturation of
      EPORs resulting from the phlebotomy-induced high EPO concentration; and 2) the
      EPOR pool is expandable not only to compensate for EPOR loss but also to adjust
      to a greater need for EPORs/progenitor cells to restore hemoglobin (Hb)
      concentration to normal levels.

PMID- 11301183
TI  - A minimal cytoplasmic subdomain of the erythropoietin receptor mediates p70 S6
      kinase phosphorylation.
AB  - Erythropoietin (EPO) is a lineage-restricted growth factor that is required for
      erythroid proliferation and differentiation. EPO stimulates the phosphorylation
      and activation of p70 S6 kinase (p70 S6K), which is required for cell cycle
      progression. Here, the minimal cytoplasmic domains of the EPO receptor (EPO-R)
      required for p70 S6K activation were determined.Ba/F3 cells were stably
      transfected with wild-type (WT) EPO-R or EPO-R carboxyl-terminal deletion
      mutants, designated by the number of amino acids deleted from the cytoplasmic
      tail (-99, -131, -221). Transfected cells were growth factor deprived and then
      stimulated with EPO. p70 S6K, JAK2, IRS-2, and ERK1/2 phosphorylation/activation
      were examined. The ability of transfected 3-phosphoinositide-dependent protein
      kinase 1 (PDK1) to reconstitute p70 S6K phosphorylation in EPO-R mutants also was
      determined. Phosphorylation and activation of p70 S6K, JAK2, IRS-2, and ERK1/2 in
      Ba/F3 cells transfected with EPO-R-99 or EPO-R-99Y343F were similar to WT EPO-R.
      In contrast, EPO-dependent p70 S6K phosphorylation/activation, as well as IRS-2
      and ERK1/2 phosphorylation, were minimal or absent in cells transfected with EPO
      R-131 or EPO-R-221. JAK2 phosphorylation was reduced significantly in cells
      transfected with EPO-R-131 and abolished with EPO-R-221. To examine the role of
      PDK1, a kinase known to phosphorylate p70 S6K, Ba/F3 EPO-R-131 cells were
      transiently transfected with PDK1. WT constitutively active PDK1 restored p70 S6K
      phosphorylation in Ba/F3 EPO-R-131 cells but not in Ba/F3 EPO-R-221 cells. The
      results demonstrate that a minimal cytoplasmic subdomain of the EPO-R extending
      between -99 and -131 is required for p70 S6K phosphorylation and activation. The
      results also demonstrate that PDK1 is a critical component in this signaling
      pathway, which requires the presence of domains between -131 and -221 for its
      activation of p70 S6K.

PMID- 11301184
TI  - Ibandronate decreases bone disease development and osteoclast stimulatory
      activity in an in vivo model of human myeloma.
AB  - The benefits of bisphosphonate therapy for multiple myeloma bone disease have
      been clearly documented. However, the effects of bisphosphonates on the
      osteoclast stimulatory activity (OSA) that is present in the marrow of patients
      with multiple myeloma, even before the bone disease is detectable, are unknown.
      Therefore, we examined the effects of ibandronate (IB) treatment prior to the
      development of bone disease in a murine model of human myeloma. Sublethally
      irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH
      77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous
      injections of IB started before or at different times after tumor injection as
      follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7;
      group 4 on day +14 after IB administration; and group 5 (control) received no IB.
      Mice were sacrificed after they developed paraplegia. The onset of paraplegia was
      delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The
      number of lytic lesions and the bone surface area of resorption (mm(2)) were
      significantly decreased in groups 1, 2, and 3, which were treated early with IB,
      when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as
      measured by the capacity of bone marrow plasma from ARH-77 mice to induce
      osteoclast (OCL) formation in human bone marrow cultures, was decreased
      proportionally to the length of IB treatment. Group 1 had the lowest OSA compared
      with the other groups (p = 0.003). However, all mice eventually developed
      paraplegia, and at time of sacrifice, tumor burden was not grossly different
      among the groups. Interestingly, macroscopic abdominal tumors were more frequent
      in mice treated with IB. These data demonstrate that early treatment of ARH-77
      mice with IB prior to development of myeloma bone disease decreases OSA and
      possibly retards the development of lytic lesions, but not eventual tumor burden.

PMID- 11301185
TI  - Acute myeloid leukemia cells are protected from spontaneous and drug-induced
      apoptosis by direct contact with a human bone marrow stromal cell line (HS-5).
AB  - In vitro culture systems that parallel in vivo growth conditions are needed to
      study leukemia biology and to accurately test therapeutic efficacies. We
      investigated the effects of the HS-5 human bone marrow stromal cell line on
      cultured primary leukemia cell survival and chemosensitivity.A total of 30 bone
      marrow (BM) samples from untreated acute myeloid leukemia (AML) patients were
      cultured for 96 hours with serum and growth factors, without HS-5, or in direct
      contact with HS-5 monolayers, or with HS-5 separated from AML cells by transwell
      inserts. In some experiments, cytosine arabinoside or daunomycin was added for
      the last 18 hours of culture. Apoptosis frequencies, bcl-2 protein expression,
      proliferating cell nuclear antigen expression, and cell cycle distributions were
      determined in four-color flow cytometry analyses of CD45(+) leukemia cells. In
      comparison to control growth conditions, direct contact with HS-5 significantly
      inhibited culture-induced and drug-induced apoptosis of AML cells. Direct contact
      of AML cells with HS-5 significantly increased short-term proliferation and
      viability, and colony formation of primary AML cells. HS-5-mediated apoptosis
      inhibition was not consistently associated with increased bcl-2 protein in AML
      cells. Noncontact conditions inhibited drug-induced apoptosis significantly less
      than direct contact with HS-5. Coculture of AML cells on HS-5 monolayers improved
      in vitro leukemia cell survival and attenuated chemotherapy-induced leukemia cell
      killing. This has practical significance, increasing the fraction of primary AML
      samples that can be analyzed in vitro, and allows drug sensitivity testing in
      growth conditions more similar to the bone marrow microenvironment.

PMID- 11301186
TI  - Effect of granulocyte colony-stimulating factor mobilization on phenotypical and
      functional properties of immune cells.
AB  - Some phenotypic and functional properties of lymphocytes from bone marrow or
      peripheral blood stem cell donors were compared in a randomized study. Lymphocyte
      subsets were analyzed by immunocytometry in blood harvested from bone marrow
      donors (n = 27) and from peripheral blood stem cell donors before and after
      granulocyte colony-stimulating factor mobilization (n = 23) and in bone marrow
      and peripheral blood stem cell grafts. Granulocyte colony-stimulating factor
      mobilization increased the blood T and B, but not NK, lymphocyte counts. All
      lymphocyte counts were approximately 10-fold higher in peripheral blood stem cell
      grafts than in bone marrow grafts. Analysis of CD25, CD95, HLA-DR, and CD45RA
      expression shows that T-cell activation level was lower after granulocyte colony
      stimulating factor mobilization. Similarly, granulocyte colony-stimulating factor
      reduced by twofold to threefold the percentage of interferon-gamma, interleukin
      2, and tumor necrosis factor-alpha-secreting cells within the NK, NK-T, and T
      cell subsets and severely impaired the potential for interferon-gamma production
      at the single-cell level. mRNA levels of both type 1 (interferon-gamma,
      interleukin-2) and type 2 (interleukin-4, interleukin-13) cytokines were
      approximately 10-fold lower in peripheral blood stem cell grafts than in bone
      marrow grafts. This reduced potential of cytokine production was not associated
      with a preferential mobilization of so-called "suppressive" cells (CD3+CD4-CD8-,
      CD3+CD8+CD56+, or CD3+TCRVA24+CD161+), nor with a modulation of killer cell
      receptors CD161, NKB1, and CD94 expression by NK, NK-T, or T cells. Our data
      demonstrate in a randomized setting that quantitative as well as qualitative
      differences exist between a bone marrow and a peripheral blood stem cell graft,
      whose ability to produce type 1 and type 2 cytokines is impaired.

PMID- 11301187
TI  - Identification of T-cell clones showing expansion associated with graft-vs
      leukemia effect on chronic myelogenous leukemia in vivo and in vitro.
AB  - Although the graft-vs-leukemia (GVL) effect induced by donor leukocyte infusion
      (DLI) is thought to be mediated by T cells, their features, as well as target
      molecules, remain unknown. To characterize T cells that mediate the GVL effect on
      chronic myelogenous leukemia (CML), we studied T-cell repertoire in peripheral
      blood (PB) of two patients treated with DLI for relapsed CML after allogeneic
      bone marrow transplantation. Peripheral blood mononuclear cells (PBMCs) were
      obtained at 2-week intervals following DLI and examined for the presence of
      antigen-driven T-cell proliferation using complementarity-determining region
      (CDR) 3 size spectratyping of T-cell receptor beta chain subfamilies. Both
      patients exhibited transient proliferation of a limited number of T cells at a
      certain point in time (day 132 for patient 1 and day 75 for patient 2) after DLI
      in association with a decrease in the proportion of Philadelphia chromosome (Ph)
      positive cells. In patient 2, who showed expansion of a BV16(+) T cell in PB,
      expansion of BV16(+) T cells with a similar CDR3 motif containing QDR to that of
      PB was demonstrated in the bone marrow (BM) sampled on day 33 and in the buccal
      mucosal tissue, showing chronic graft-vs-host disease (GVHD) on day 138 after
      DLI. When PBMCs obtained from patient 2 in remission were cultured with
      cryopreserved CML cells for 2 weeks, proliferation of a BV16(+) T cell with a
      CDR3 motif of QIR was induced in vitro. These findings indicate that transient
      proliferation of a limited number of T cells detected in PB 3-5 months after DLI
      probably reflects the GVL response against CML cells and may serve as a marker
      for the appearance of the GVL effect induced by DLI.

PMID- 11301188
TI  - Pro-apoptotic and anti-apoptotic effects of transferrin and transferrin-derived
      glycans on hematopoietic cells and lymphocytes.
AB  - The aim of this study was to test the hypothesis that transferrin (Tf) has anti
      apoptotic properties and thereby exerts a cytoprotective effect against tissue
      damage induced by irradiation and other cytotoxic modalities. This hypothesis was
      tested in several models, including in vitro human short-term marrow cultures,
      subpopulations of marrow cells, particularly, CD56(+) natural killer cells (and
      natural killer cell lines), and in vivo radioprotection of murine marrow cells.
      Reverse transcriptase polymerase chain reaction analysis was used for
      determination of cytokine mRNA. Preincubation of human marrow with Tf protected
      cells (except for a CD56(+) subpopulation) against cell death induced by gamma
      irradiation, tumor necrosis factor-alpha (TNF-alpha), and agonistic anti-Fas
      monoclonal antibody. Deglycosylation of Tf abrogated this action of Tf;
      conversely, Tf-derived glycans (Tf-Gly) (but not glycans isolated from other
      proteins) mimicked the effects of the intact Tf molecule on apoptosis. Antibodies
      specific for the Tf receptor (CD71) did not block the effects of Tf or Tf-Gly on
      apoptosis. Determination of cytokine mRNA in the course of Fas-mediated apoptosis
      in the presence of Tf or Tf-Gly showed upregulation of mRNA for Fas ligand and
      TNF-alpha in CD56(+) and downregulation of these transcripts along with
      upregulation of mRNA for interleukin-10 in CD3(+) marrow cells. Under these
      conditions, a distinct increase in Fas-associated phosphatase-1 message was
      observed in CD3(+) cells that were protected by Tf or Tf-Gly against apoptosis.
      The in vitro data were confirmed in a murine in vivo model in which pretreatment
      of mice with Tf protected marrow cells against gamma-irradiation-induced cell
      death. These data suggest a role for Tf and particularly Tf-Gly in the regulation
      of programmed cell death, apparently via alterations in cytokine expression, and
      provide a basis for additional studies on the use of Tf in cytoprotective
      protocols.

PMID- 11301189
TI  - Novel expression of cyclin-dependent kinase inhibitors in human B-cell
      precursors.
AB  - Eukaryotic cell division is regulated by cyclins, cyclin-dependent kinases (CDK),
      and cyclin-dependent kinase inhibitors (CKI). Genes encoding these proteins are
      mutated or deleted in many types of cancer. For example, 20%-30% of B-lineage
      acute lymphoblastic leukemias (ALL) have deletions in the CKI known as INK4a. The
      contribution of INK4a deletions to the progression of B-lineage ALL is uncertain,
      partially due to a paucity of data on expression in normal B-cell precursors. We
      therefore conducted a comparative analysis of normal and leukemic human B-cell
      development for the expression of cyclins, CDK, and CKI. Specific stages of human
      B-cell development from normal bone marrow were purified by fluorescence
      activated cell sorting. The sorted populations and B-lineage ALL cell lines (BLIN
      1, 2, 3, 4) were examined for expression of cyclins, CDK, and CKI by reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blotting.RT-PCR
      analysis showed that cyclin D2, cyclin D3, CDK4, and CDK6 were ubiquitously
      expressed in normal B-cell development and in the BLIN ALL cell lines. The
      p19(INK4d) CKI was the most commonly expressed member of the INK4 family, whereas
      p16(INK4a) was more weakly and variably expressed. Expression of the p57(KIP2)
      CKI varied as a function of the stage of B-cell development. Analysis of normal B
      cell precursors by Western blotting indicated that CDK4, CDK6, p19(INK4d), and
      p57(KIP2) were expressed, whereas p16(INK4a) was not detected. Cyclin D/CDK
      expression in normal and leukemic human B-cell precursors is similar to
      expression of these proteins in human and murine mature B cells. In contrast, the
      ubiquitous expression of p19(INK4d) has not been previously described in human or
      murine B-lineage cells. Our results suggest that loss of INK4a may only minimally
      contribute to tumor cell progression in B-lineage ALL, since expression of INK4d
      could provide a compensatory function as a cyclin-dependent kinase inhibitor.

PMID- 11301190
TI  - T-cell factor-1 expression during human natural killer cell development and in
      circulating CD56(+) bright natural killer cells.
AB  - Transcription factors are essential to govern differentiation along the lymphoid
      lineage from uncommitted hematopoietic stem cells. Although many of these
      transcription factors have putative roles based on murine knockout experiments,
      their function in human lymphoid development is less known and was studied
      further. Transcription factor expression in fresh and cultured adult human bone
      marrow and umbilical cord blood progenitors was evaluated. We found that fresh
      CD34(+)Lin(-) cells that are human leukocyte antigen (HLA)-DR(-) or CD38(-)
      constitutively express GATA-3 but not T-cell factor-1 (TCF-1) or Id-3. Culture
      with the murine fetal liver cell line AFT024 and defined cytokines was capable of
      inducing TCF-1 mRNA. However, no T-cell receptor gene rearrangement was
      identified in cultured progeny. Id-3, a basic helix loop helix factor with
      dominant negative function for T-cell differentiation transcription factors, also
      was upregulated and may explain unsuccessful T-cell maturation. To better
      understand the developmental link between natural killer (NK) cells derived from
      progenitors, we studied NK cell subsets circulating in blood. CD56(+bright), but
      not CD56(+dim), NK cells constitutively express TCF-1 by reverse transcriptase
      polymerase chain reaction and Western blot analysis. The TCF-1 isoform found in
      CD56(+bright) cells, which express lectin but not immunoglobulin class I
      recognizing inhibitory receptors, was identical to that induced in NK cell
      differentiation culture and was distinctly different from isoforms in T cells.
      These results suggest that TCF-1 does not target human killer immunoglobulin
      receptor genes, TCF-1 is uniquely expressed in circulating CD56(+bright) NK
      cells, and specific TCF-1 isoforms may play an important role in regulating NK
      differentiation from a common NK/T-cell progenitor.

PMID- 11301191
TI  - A role of jumonji gene in proliferation but not differentiation of megakaryocyte
      lineage cells.
AB  - In this study, megakaryocytopoiesis was investigated in the recessive mutant
      mouse, jumonji, obtained by a gene-trap strategy. We investigated the number of
      megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood of
      jumonji homozygous embryos by in vitro colony forming assay and monitored colony
      formation from single megakaryocyte progenitors. We also investigated the
      differentiation of jumonji-deficient megakaryocytes in terms of the expression of
      megakaryocyte differentiation markers PF4, CD62P, and GATA-1, proplatelet
      formation, cytoplasmic maturation, and endomitosis. We found that the population
      of megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood
      of jumonji homozygotes increased. A fraction of megakaryocyte progenitors derived
      from the fetal liver of jumonji homozygotes formed larger colonies in vitro when
      compared with controls. This abnormality is caused by delayed growth arrest in
      the progeny. Immature megakaryocyte progenitors showed this abnormality. The
      megakaryocytes of jumonji homozygotes expressed PF4, CD62P, and GATA-1, obtained
      cytoplasmic maturation, extended proplatelet-like processes, and underwent
      endomitosis. The loss of the jumonji gene causes an increase in the number of
      megakaryocyte lineage cells. Our data suggest that the jumonji gene regulates
      proliferation but not differentiation of megakaryocyte lineage cells.

PMID- 11301192
TI  - Cell cycle activation of hematopoietic progenitor cells increases very late
      antigen-5-mediated adhesion to fibronectin.
AB  - Recent studies suggested that trafficking of hematopoietic progenitor cells is
      related to cell cycle status. We studied whether adhesion of progenitor cells to
      extracellular matrix proteins was modulated by cell cycle transit. Mobilized
      peripheral blood CD34+ cells were stimulated ex vivo for 48 hours with stem cell
      factor, flt-3 ligand, and thrombopoietin and fractionated by adhesion to
      fibronectin or vascular cell adhesion molecule-1 (VCAM-1). Adherent and
      nonadherent cells were assayed for cell cycle status, long-term culture
      initiating cell frequency, and integrin function. Binding to fibronectin, but not
      to VCAM-1, displayed a cell cycle selectivity as the adherent fraction to
      fibronectin was enriched in cycling CD34+ cells and in cycling long-term culture
      initiating cells compared to the nonadherent fraction. Combined cell cycle and
      phenotypic analysis showed that the expression of VLA-5 was upregulated during
      S/G2+M but that of VLA-4 remained constant. The selective binding of cycling
      CD34+ cells to fibronectin was reverted by anti-VLA-5 but not by anti-VLA-4
      blocking antibodies. Also, cycling CD34+ cells preferentially adhered to the VLA
      5 binding domain but not to the VLA-4 binding domain of fibronectin. Adhesion of
      cycling CD34+ cells to fibronectin was a reversible process modulated by cell
      cycle progression, because adherent cells could exit the cell cycle and return to
      a nonadhesive state within an additional 48-hour culture period. The results
      indicate that the enhanced binding capacity of cycling progenitor cells to
      fibronectin is mediated by VLA-5.

PMID- 11301193
TI  - Differences in cell cycle kinetics of candidate engrafting cells in human bone
      marrow and mobilized peripheral blood.
AB  - Patients undergoing hematopoietic stem cell transplantation (HSCT) with mobilized
      peripheral blood (MPB) engraft quicker than those receiving bone marrow (BM). Our
      objective was to determine whether candidate engrafting cells--primitive
      hematopoietic progenitors (PHPs)--from MPB and BM exhibit different responses to
      cytokines that could explain this observation. We compared the cell cycle
      kinetics and ex vivo expansion of PHP-enriched cells obtained from MPB (n = 12)
      and BM (n = 10) by fluorescence-activated sorting of CD90+, AC133+ or CD38(dull)
      subsets of pre-selected CD34(+) cells. Cell cycle status, before and after 40
      hours of serum-free culture with a cytokine cocktail, was assessed by
      multiparameter flow cytometry following incubation with Hoechst 33342 and pyronin
      Y. We found that 0.2% +/- 0.3% of MPB CD34(+)CD90(+) cells were in S/G(2)/M
      phases at hour 0, compared with 5% +/- 2.5% of those from BM (p = 0.0001), and
      86.3% +/- 9.7% were in G(0), compared with 65.3% +/- 10% of those in BM (p =
      0.0001). After 40 hours of culture, CD34(+)CD90(+) cells from MPB were more
      mitotically active than those from BM, with 29% +/- 4.9% in S/G(2)/M and 20% +/-
      11.4% in G(0), compared to 19% +/- 6.5% (p = 0.001) and 39.2% +/- 22% (p = 0.027)
      of cells from BM. There was greater expansion of both total CD34(+) cells and the
      CD90(+) subset from MPB samples (p = 0.001 and 0.0001, respectively). Results
      from PHPs defined on the basis of AC133 expression correlated well with results
      obtained in CD90(+) subsets (r(2) = 0.81; p = 0.014).MPB PHPs appear to be primed
      for a greater acceleration in mitotic activity upon cytokine exposure. This
      qualitative difference may contribute to the earlier engraftment seen after HSCT
      using MPB grafts.

PMID- 11301194
TI  - Combined host-conditioning with CTLA4-Ig, tacrolimus, anti-lymphocyte serum, and
      low-dose radiation leads to stable mixed hematopoietic chimerism.
AB  - The toxic dose of irradiation required to achieve stable mixed hematopoietic
      chimerism is the major limitation to its clinical application in transplantation
      and other nonmalignant conditions such as hemoglobinopathies. This study examines
      the additive effect of costimulatory blockage, to our previously described
      tacrolimus-based conditioning regimen, in further reducing the dose of total-body
      irradiation to achieve stable mixed chimerism in rats. Fully mismatched, 4- to 6
      week-old ACI and Wistar Furth rats were used as donors and recipients,
      respectively. Recipients were administered CTLA4-Ig 2mg/kg/day (alternate days)
      in combination with tacrolimus 1 mg/kg/day (daily) from day 0 through day +10,
      anti-lymphocyte serum 10 mg at day +10 (single dose), and total-body irradiation
      ranging from 100-600 cGy, prior to bone marrow transplantation (day 0) with 100 x
      10(6) of T-cell-depleted bone marrow cells. Levels of donor chimerism were
      determined over a period of 12 months. The short course of CTLA4-Ig, tacrolimus,
      and ALS led to dramatic engraftments at reduced doses of irradiation: 100% (5/5)
      and 93% (13/14) of the animals developed mixed chimerism at 400 cGy and 300 cGy,
      respectively. At 300 cGy, recipients exhibited durable, multilineage mixed
      chimerism at 365 days with donor cells ranging from 19-42% (mean 23.4%) with no
      evidence of graft-vs-host disease. These mixed chimeras exhibited in vitro (mixed
      lymphocyte reaction) and in vivo (skin grafts) donor-specific tolerance. This
      study suggests that addition of costimulatory blockade to a tacrolimus-based
      conditioning regimen reduces the dose of irradiation required to achieve stable
      multilineage chimerism in rats.

PMID- 11301195
TI  - Evolution tunes the excitability of individual neurons.
AB  - The relationship between the genome and the evolution of the nervous system may
      differ between an animal like C. elegans with 302 neurons, and mammals with tens
      of billions of neurons. Here we report that a class of nonconserved potassium
      channels highly expanded in C. elegans may play a special role in the evolution
      of its nervous system. The C. elegans genome contains an extended gene family of
      potassium channels whose members fall into two evolutionary divergent classes.
      One class constitutes an ancient conserved "set" of K+ channels with orthologues
      in both humans and Drosophila and a second larger class made up of rapidly
      evolving genes unique to C. elegans. Chief among this second class are novel
      potassium channels having four transmembrane domains per subunit that function as
      regulated leak conductances to modulate cell electrical excitability. This
      inventory of novel potassium channels is far larger in C. elegans than in humans
      or Drosophila. We found that, unlike conserved channel genes, the majority of
      these genes are expressed in very few cells. We also identified DNA enhancer
      elements associated with these genes that direct gene expression to individual
      neurons. We conclude that C. elegans may maintain an exceptionally large
      inventory of these channels (as well as ligand-gated channels) as an adaptive
      mechanism to "fine tune" individual neurons, making the most of its limited
      circuitry.

PMID- 11301196
TI  - Recognition of Mother's voice evokes metabolic activation in the medial
      prefrontal cortex and lateral thalamus of Octodon degus pups.
AB  - In a variety of animal species, including primates, vocal communication is an
      essential part to establish and maintain social interactions, including the
      emotional bond between the newborn, its parents and siblings. The aim of this
      study in pups of the trumpet-tailed rat, Octodon degus, was to identify cortical
      and subcortical brain regions, which are involved in the perception of
      vocalizations uttered by the mother. In this species, which is characterized by
      an elaborated vocal repertoire, the (14C)-2-fluoro-deoxyglucose autoradiography
      was applied to measure region-specific metabolic activation in response to the
      presentation of a learned emotionally relevant acoustic stimulus, the maternal
      calls. Already at the age of eight days the precentral medial cortex, anterior
      cingulate cortex and the lateral thalamus could be identified by their enhanced
      metabolic activation in response to the presentation of the emotionally relevant
      maternal nursing calls, whereas other brain areas, such as the hippocampus and
      amygdala did not show stimulus-induced activation. Since in humans changes of
      activity patterns in relation to the emotional content of spoken language have
      been observed in similar brain regions, e.g. in the anterior cingulate cortex,
      Octodon degus may provide a suitable animal model to study the cellular and
      synaptic mechanisms underlying perception, production and processing of
      conspecific vocalizations.

PMID- 11301197
TI  - Efficient in utero gene transfer system to the developing mouse brain using
      electroporation: visualization of neuronal migration in the developing cortex.
AB  - We report a novel gene transfer system using electroporation. We used this
      technique to introduce a marker gene plasmid containing enhanced green
      fluorescent protein into mouse brains at embryonic day 12-17 without removing the
      embryos from the uterus. The embryos were allowed to continue to develop in
      utero, and more than 80% were born normally expressing the exogenous gene.
      Enhanced green fluorescent protein driven by the cytomegalovirus promoter was
      strongly expressed in the ventricular zone, radial fibers and migrating
      neuroblasts, but not in mature neurons, suggesting that the cytomegalovirus
      promoter is silenced after the cells differentiate into mature neurons. Since
      there is still no convenient way of visualizing the migrating neuroblasts,
      especially of distinguishing them from the surrounding mature neurons in the
      cortical plate, this system should provide a good tool for analysing neuronal
      migration. In the postnatal lateral cortex, neuroblasts migrated almost
      "tangentially" along the obliquely running "radial" fibers beneath the cortical
      plate, and after entering the cortical plate, turned towards the marginal zone
      and migrated radially. Neurons with primitive dendrites were observed only along
      the border between the marginal zone and the cortical plate, and never at other
      sites, such as in the middle of the cortical plate. These results imply that the
      neuroblasts do terminate migration and start differentiation to mature neurons
      when they encounter the marginal zone, as has long been suggested. By contrast,
      when elongation factor 1alpha promoter was used, prominent fluorescence allowed
      visualization of the entire mature neurons as well. The labeled neurons were
      observed to send axons to the contralateral cortex where they arborized
      extensively.Thus, this system is much easier and more efficient than virus
      mediated gene transfer, and is useful for gain-of-function analysis of neural
      cell fate determination, migration, positioning and axon path-finding in mouse
      embryos.

PMID- 11301198
TI  - The dynamics of blood-brain barrier breakdown in an experimental model of glial
      cell degeneration.
AB  - This study was undertaken to investigate the dynamics of blood-brain barrier
      breakdown in an in vivo rat model of selective CNS vulnerability. 1,3
      Dinitrobenzene was used to induce rapid glial degeneration in highly defined
      areas of the brainstem. Leakage of fluorescent dextran was used to demonstrate
      the breakdown of the blood-brain barrier, and antibodies to glial and neuronal
      specific proteins to assess the accompanying cell changes. Beginning 18 h after a
      toxic dose of dinitrobenzene and before loss of glial ensheathment, a sub
      population of blood vessels became permeable to fluorescent dextrans below
      500,000 mol. wt in size. By 24h most macroglial cells had been lost from within
      susceptible areas and vascular leakage had reached peak levels. Macrophage
      invasion was detected three days following dinitrobenzene. Vessels continued to
      leak up to four days after the lesion was formed, but by six days blood-brain
      barrier integrity was largely re-established. Multiple tracer injections over
      time demonstrated that a single sub-population of vessels was leaking during the
      experimental period. From these findings we conclude that blood-brain barrier
      breakdown in this model system is highly selective, graded in extent and
      molecular weight specificity and not a direct consequence of astrocyte
      degeneration or microglial activation. This system could be useful in modeling
      human CNS pathological processes with a vascular component and for understanding
      in vivo glial blood-brain barrier interactions.

PMID- 11301199
TI  - Expression of presenilin-1 and Notch-1 receptor in human embryonic CNS.
AB  - In vitro studies have shown that the Alzheimer's disease-related presenilin-1
      protein can mediate Notch-1 receptor cleavage during signalling. In the present
      study, we compared the distribution of presenilin-1 and Notch-1 receptor
      immunoreactivities in human embryonic CNS tissue during the first trimester of
      development. Our aim was to gain insight into whether these proteins are likely
      to interact functionally during human fetal brain development. CNS material was
      obtained from routine abortions, cryosectioned and studied by means of
      immunohistochemistry with antibodies to presenilin-1 and Notch-1. At very early
      stages of embryonic development (four to five gestational weeks) intensive
      presenilin-1 immunoreactivity could be seen predominantly in neurites in the
      ventral horn of the spinal cord, where it overlapped with 200-kDa neurofilament
      immunoreactivity. Presenilin-1 immunoreactivity was also seen in neuroblasts of
      the ventricular zone of the tel- and mesencephalon, as well as of the brainstem.
      Notch-1 receptor appeared in neuronal and ependymal cells throughout the CNS.
      Seven- to eight-week CNS tissue showed similar patterns of presenilin-1 and Notch
      1 receptor expression in the spinal cord and cerebral cortex as was seen at five
      weeks. Both proteins were localised in the neuroepithelial cell layer lining the
      ventricles, as well as in the cortical plate layer, where immunoreactivity was
      seen in the cell bodies. In addition, presenilin-1 immunoreactivity was seen in
      thin neurites in the subplate of the developing cortex. At 10 weeks, presenilin-1
      immunoreactivity was reduced in the spinal cord. These results show that,
      although presenilin-1 and Notch-1 receptor are localised to the same
      differentiating cell populations in the human cerebral cortex, making a direct
      interaction possible, these proteins are otherwise confined to different neurons
      or neuronal compartments, suggesting a role for presenilin-1 during early CNS
      differentiation that does not involve Notch-1 receptor processing. Double
      staining for presenilin-1 in the endoplasmic reticulum and presenilin-1 in the
      Golgi showed overlap to some extent in investigated CNS regions, but not in
      neurites. This suggests that presenilin-1 function during neurogenesis is not
      exclusively correlated to protein processing within the endoplasmic reticulum and
      Golgi, but that presenilin-1 may also be involved in other processes, such as
      axonal and dendritic outgrowth or synaptic formation. In summary, our findings
      provide supportive evidence that the presenilin-1 protein is involved in the
      development and maturation of the human fetal CNS. The presence of presenilin-1
      immunoreactivity in both the cell bodies and neurites of developing neurons
      strongly suggests divergent mechanisms of function for presenilin-1 during human
      brain development. These may include interactions with any of the Notch receptor
      proteins, as well as Notch-independent mechanisms.

PMID- 11301200
TI  - Distribution and expression of TREK-1, a two-pore-domain potassium channel, in
      the adult rat CNS.
AB  - TREK-1 is a member of the two-pore-domain potassium channel family which is
      expressed predominantly in the CNS. Using an anti-peptide polyclonal antiserum,
      we have determined the distribution of TREK-1 in the brain and spinal cord of
      adult rats. Specificity of the antiserum was tested using a TREK-1-transfected
      cell line and confirmed with c-myc-tagged TREK-1. In thin tissue sections,
      immunoreactivity was widespread throughout the rat brain and spinal cord. TREK-1
      like signals were observed in the cerebral cortex, basal ganglia, hippocampus,
      and various other subcortical nuclei in the hypothalamus, thalamus, mesencephalon
      and rhombencephalon. TREK-1 labelling appeared to be over the entire cell
      membrane, including the cell body and processes. Cells that morphologically
      resembled projection neurones and interneurones but not glial cells were
      labelled. As interneurones and known GABAergic projection neurones were the
      predominant population labelled, we investigated the possibility that TREK-1 is
      expressed in GABA-containing neurones using a specific anti-GABA antiserum.
      Expression of TREK-1 in GABA-containing neurones was observed in a number of
      areas, including the isocortex, hippocampus and thalamus. Thus, TREK-1 expression
      defines a unique and specific subset of interneurones and principal cells. These
      studies indicate a widespread distribution of TREK-1 potassium channels
      throughout the rat brain and spinal cord, with expression in a number of areas
      being demonstrated to be present on GABA-containing neurones.

PMID- 11301201
TI  - Evidence of altered inhibition in layer V pyramidal neurons from neocortex of
      Kcna1-null mice.
AB  - Mice lacking the potassium channel subunit KCNA1 exhibit a severe epileptic
      phenotype beginning at an early postnatal age. The precise cellular physiological
      substrates for these seizures are unclear, as is the site of origin. Since KCNA1
      mRNA in normal mice is expressed in the neocortex, we asked whether neurons in
      the neocortex of three to four week-old Kcna1-null mutants exhibit evidence of
      hyperexcitability. Layer V pyramidal neurons were directly visualized in brain
      slices with infrared differential-interference contrast microscopy and evaluated
      with cellular electrophysiological techniques. There were no significant
      differences in intrinsic membrane properties and action potential shape between
      Kcna1-null and wild-type mice, consistent with previous findings in hippocampal
      slice recordings. However, the frequency of spontaneous post-synaptic currents
      was significantly higher in Kcna1-null compared to wild-type mice. The frequency
      of spontaneous inhibitory post-synaptic currents and miniature (action-potential
      independent) inhibitory post-synaptic currents was also significantly higher in
      Kcna1-null compared to wild-type mice. However, the frequency of spontaneous and
      miniature excitatory post-synaptic currents was not different in these two groups
      of animals. Comparison of the amplitude and kinetics of miniature inhibitory and
      excitatory post-synaptic currents revealed differences in amplitude, rise time
      and half-width between Kcna1-null and wild-type mice. Our data indicate that the
      inhibitory drive onto layer V pyramidal neurons is increased in Kcna1 knockout
      mice, either directly through an increased spontaneous release of GABA from
      presynaptic terminals contacting layer V pyramidal neurons, or an enhanced
      excitatory synaptic input to inhibitory interneurons.

PMID- 11301202
TI  - Unilateral induced neocortical malformation and the formation of ipsilateral and
      contralateral barrel fields.
AB  - Freezing lesions to the developing cortical plate of rodents results in a focal
      malformation resembling human 4-layered microgyria, and this malformation has
      been shown to result in local and widespread disruptions of neuronal
      architecture, connectivity, and physiology. Because we had previously
      demonstrated that microgyria caused disruptions in callosal connections, we
      hypothesized that freeze lesions to the postero-medial barrel sub-field (PMBSF)
      in one hemisphere would affect the organization of this barrel field
      contralaterally. We placed freeze lesions in the presumptive PMBSF of neonatal
      rats and, in adulthood, assessed the architecture of the ipsilateral and
      contralateral barrel fields. Malformations in the PMBSF resulted in a substantial
      decrease in the number of barrels as identified by cytochrome oxidase activity.
      More importantly, we found an increase in the total area of the contralateral
      PMBSF, although there was no difference in individual barrel cross-sectional
      areas, indicating an increase in the area of inter-barrel septae. This increase
      in the septal area of the contralateral PMBSF is consistent with changes in
      callosal and/or thalamic connectivity in the contralateral hemisphere. These
      results are another example of both local and widespread disruption of
      connectional architecture following induction of focal microgyria.

PMID- 11301203
TI  - Interactive effects of nicotine and alcohol co-administration on expression of
      inducible transcription factors in mouse brain.
AB  - Nicotine and alcohol are abused substances that are often used concurrently.
      Despite their combined usage, little is known about how they interact to produce
      changes in behavior and neural activity. Two experiments were conducted to
      identify interactions on both behavior and neural targets resulting from the co
      administration of nicotine and alcohol. In Experiment 1, male C57BL/6J mice were
      administered saline, alcohol (2.4 g/kg, i.p.), nicotine (0.5 mg/kg, i.p.) or an
      alcohol/nicotine mixture and returned to their home cage. In Experiment 2, a
      higher dose of nicotine (1.0 mg/kg, i.p.) was included and animals were exposed
      to a novel environment. Several behavioral measures were analysed during novelty
      exposure. Immunohistochemical detection of inducible transcription factors (c-Fos
      and Egr1) was used in both experiments to identify changes in neural activation.
      Behavioral results suggested that the drugs were interacting in the production of
      behaviors. In particular, alcohol produced locomotor stimulation while it
      suppressed counts of rearing and leaning. When co-administered, nicotine appeared
      to counteract the alcohol-enhanced locomotor activity. Several brain regions were
      observed to have altered transcription factor expression in response to the
      different drug treatments, including amygdalar, hippocampal and cortical
      subregions. In a subset of these brain areas, nicotine and alcohol counteracted
      one another in the expression of transcription factors. These results identify
      several interactive target sites within the hippocampus, extended amygdala and
      cortical regions. The interactions appear to be a result of antagonizing actions
      of nicotine and alcohol. Finally, the results suggest that the combined use of
      nicotine and alcohol may offset the effects of the drug administered
      independently.

PMID- 11301204
TI  - Long-lasting induction of brain-derived neurotrophic factor is restricted to
      resistant cell populations in an animal model of status epilepticus.
AB  - We have recently characterized an animal model of status epilepticus induced by a
      single intraseptal injection of kainate. Under these conditions, there is a
      delayed expanding apoptotic hippocampal and amygdalar cell death. In order to
      further characterize this animal model, we have performed a detailed time-course
      analysis of the appearance of cell death, brain-derived neurotrophic factor
      messenger RNA expression and astroglial and microglial response in different
      brain areas related to the limbic system. We found a long-lasting delayed
      apoptotic cell death in the hippocampal formation, amygdala, medial thalamus,
      dorsal endopiriform nucleus and multiple cortical areas from two to 21 days post
      injection. There was a spatiotemporal correlation between the appearance of cell
      death and induction of brain-derived neurotrophic factor messenger RNA expression
      in the areas studied, and interestingly this induction was found in non
      degenerating cells. We conclude that our animal model of status epilepticus
      exhibits remarkable features of recurrent seizure activity and provides evidence
      for a neuroprotective role of brain-derived neurotrophic factor against seizure
      induced apoptotic cell death.

PMID- 11301205
TI  - Effects of ion channel blockade on the distribution of Na, K, Ca and other
      elements in oxygen-glucose deprived CA1 hippocampal neurons.
AB  - The pathophysiology of brain ischemia and reperfusion injury involves
      perturbation of intraneuronal ion homeostasis. To identify relevant routes of ion
      flux, rat hippocampal slices were perfused with selective voltage- or ligand
      gated ion channel blockers during experimental oxygen-glucose deprivation and
      subsequent reperfusion. Electron probe X-ray microanalysis was used to quantitate
      water content and concentrations of Na, K, Ca and other elements in morphological
      compartments (cytoplasm, mitochondria and nuclei) of individual CA1 pyramidal
      cell bodies. Blockade of voltage-gated channel-mediated Na+ entry with
      tetrodotoxin (1 microM) or lidocaine (200 microM) significantly reduced excess
      intraneuronal Na and Ca accumulation in all compartments and decreased respective
      K loss. Voltage-gated Ca2+ channel blockade with the L-type antagonist
      nitrendipine (10 microM) decreased Ca entry and modestly preserved CA1 cell
      elemental composition and water content. However, a lower concentration of
      nitrendipine (1 microM) and the N-, P-subtype Ca2+ channel blocker omega
      conotoxin MVIIC (3 microM) were ineffective. Glutamate receptor blockade with the
      N-methyl-D-aspartate (NMDA) receptor-subtype antagonist 3-(2-carboxypiperazin-4
      yl) propyl-1-phosphonic acid (CPP; 100 microM) or the alpha-amino-3-hydroxy-5
      methyl-4-isoazole propionic acid (AMPA) receptor subtype blocker 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX; 10 microM/100 microM glycine) completely
      prevented Na and Ca accumulation and partially preserved intraneuronal K
      concentrations. Finally, the increase in neuronal water content normally
      associated with oxygen-glucose deprivation/reperfusion was prevented by Na+
      channel or glutamate receptor blockade. Results of the present study demonstrate
      that antagonism of either postsynaptic NMDA or AMPA glutaminergic receptor
      subtypes provided nearly complete protection against ion and water deregulation
      in nerve cells subjected to experimental ischemia followed by reperfusion. This
      suggests activation of ionophoric glutaminergic receptors is involved in loss of
      neuronal osmoregulation and ion homeostasis. Na+ channel blockade also
      effectively diminished neuronal ion and water derangement during oxygen-glucose
      deprivation and reperfusion. Prevention of elevated Nai+ levels is likely to
      provide neuroprotection by decreasing presynaptic glutamate release and by
      improving cellular osmoregulation, adenosine triphosphate utilization and Ca2+
      clearance. Thus, we suggest that voltage-gated tetrodotoxin-sensitive Na+
      channels and glutamate-gated ionotropic NMDA or AMPA receptors are important
      routes of ion flux during nerve cell injury induced by oxygen-glucose
      deprivation/reperfusion.

PMID- 11301206
TI  - Selective destruction of medial septal cholinergic neurons attenuates pyramidal
      cell suppression, but not excitation in dorsal hippocampus field CA1 induced by
      subcutaneous injection of formalin.
AB  - Using extracellular recording techniques in urethane- (1g/kg, i.p.) anaesthetized
      rats, we investigated the influence exercised by medial septal cholinergic
      neurons on dorsal hippocampus field CA1 neural responses to a hind paw injection
      of formalin (5%, 0.05 ml, s.c.). Cholinergic neurons of the medial septal region
      were destroyed by local microinjection of the immunotoxin 192 IgG-saporin.
      Compared to control vehicle microinjected animals, immunotoxin-treatment
      attenuated the amplitude, but not frequency, of CA1 theta induced by intraseptal
      injection of carbachol. This suggested a selective destruction of medial septal
      cholinergic neurons by the immunotoxin. Such destruction also abolished; (i)
      intraseptal carbachol-induced suppression of CA1 population spike, and (ii)
      stimulation-intensity dependent increase in amplitude, but not frequency, of
      theta evoked on electrical stimulation in the region of oral part of pontine
      reticular nucleus. Further, in comparison to vehicle-treated animals, selective
      cholinergic destruction attenuated formalin-induced; (i) theta activation, (ii)
      suppression of CA1 pyramidal cell population spike and dendritic field excitatory
      post-synaptic potential, (iii) inhibition of complex spike cell extracellular
      activity, and (iv) excitation and theta-rhythmicity of local putative GABAergic
      interneurons. However, pretreatment with the immunotoxin did not alter the
      strength and proportion of complex spike cells excited following injection of
      formalin. From these findings we suggest that medial septal cholinergic neurons
      mediate, at least partly, the amplitude of theta and pyramidal cell suppression
      via an inhibitory network involving CA1 interneurons. The data also indicates
      that during formalin theta, the cholinergic-mediated inhibitory processing does
      not modulate the strength and selectivity of complex spike cell excitation. This
      points to formalin-induced, non-overlapping inhibitory and excitatory processes
      that might have different functional relevance.

PMID- 11301207
TI  - Developmental restriction of the LIM homeodomain transcription factor Islet-1
      expression to cholinergic neurons in the rat striatum.
AB  - LIM homeodomain transcription factors play crucial roles in determining diverse
      aspects of neuronal development both in vertebrates and invertebrates. In the
      present study, we studied the expression pattern of Islet-1 (Isl-1), a member of
      the LIM homeodomain protein family, in the rat striatum during development. The
      developmental expression of Isl-1 in the striatum is highly dynamic and complex
      in terms of spatial and temporal regulation. The reverse transcription-polymerase
      chain reaction and ribonuclease protection assays demonstrated that Isl-1
      messenger RNA was expressed in the developing striatum. The immunocytochemical
      study of Isl-1 protein expression showed that there were prominent mediolateral
      and caudorostral Isl-1 gradients in the developing striatum. Numerous Isl-1
      positive cells appeared in the medial mantle zone of the developing striatal
      proper, and they co-expressed the postmitotic neuronal marker, microtubule
      associated protein 2. The numbers of Isl-1-positive cells were decreased from the
      medial to the lateral regions, so that there were only a few Isl-1-positive cells
      scattered in the lateral striatum. These scattered Isl-1-positive cells were
      doubly labeled with tyrosine kinase receptor A and choline acetyltransferase,
      which indicated that they were cholinergic neurons. The Isl-1 gradients were most
      prominent in the embryonic day 18 and 20 striatum. With increases of time, the
      Isl-1 gradients were gradually reduced, and the gradients disappeared by
      postnatal day 7. Despite the general down-regulation of striatal Isl-1, a few Isl
      1-positive cells were sustained into the adult striatum in which Isl-1 was nearly
      exclusively expressed by all cholinergic neurons and vice versa. Our study
      suggests that Isl-1 is likely to be initially expressed by postmitotic
      cholinergic precursors and some, if not all, non-cholinergic precursors in the
      developing striatum. During the progression of striatal differentiation, Isl-1 is
      down-regulated in non-cholinergic cells, but is sustained in cholinergic cells.
      The developmental restriction of Isl-1 to cholinergic neurons in the striatum may
      represent a novel mechanism by which LIM homeodomain proteins specify specific
      cell types in the striatum during development.

PMID- 11301208
TI  - Coordinated expression of muscarinic receptor messenger RNAs in striatal medium
      spiny neurons.
AB  - The postsynaptic effects of acetylcholine in the striatum are largely mediated by
      muscarinic receptors. Two of the five cloned muscarinic receptors (M1 and M4) are
      expressed at high levels by the medium spiny neurons-the principal projection
      neurons of the striatum. Previous studies have suggested that M4 muscarinic
      receptors are found primarily in medium spiny neurons that express substance P
      and participate in the "direct" striatonigral pathway. This view is difficult to
      reconcile with electrophysiological studies suggesting that nearly all medium
      spiny neurons exhibit responses characteristic of M4 receptors. To explore this
      apparent discrepancy, the coordinated expression of M1-M5 receptor messenger RNAs
      in identified medium spiny neurons was assayed using single-cell reverse
      transcription-polymerase chain reaction techniques. Nearly all medium spiny
      neurons had detectable levels of M1 receptor messenger RNA. Although M4 receptor
      messenger RNA was detected more frequently in substance P-expressing neurons
      (70%), it was readily seen in a substantial population of enkephalin-expressing
      neurons (50%). To provide a quantitative estimate of transcript abundance,
      quantitative reverse transcription-polymerase chain reaction experiments were
      performed. These studies revealed that M4 messenger RNA was expressed by both
      substance P and enkephalin neurons, but was roughly five-fold higher in abundance
      in substance P-expressing neurons. This quantitative difference provides a means
      of reconciling previous estimates of M4 receptor distribution and function.

PMID- 11301209
TI  - Sex steroids modulate luteinizing hormone-releasing hormone secretion in a
      cholinergic cell line from the basal forebrain.
AB  - The function of a particular neuronal population is in part determined by its
      neurotransmitter phenotype. We have found that a neuronal-derived septal cell
      line (SN56), known for its cholinergic properties, also synthesizes and releases
      luteinizing hormone-releasing hormone. In addition, these cells express the
      messenger RNAs encoding estrogen and progesterone receptors. The activation of
      these receptors by their respective ligands cooperatively modulates the
      depolarization-induced release of luteinizing hormone-releasing hormone in these
      cells. We have also found that a number of septal neurons in postnatal (1-week
      old) mice are immunoreactive to both choline acetyltransferase and luteinizing
      hormone-releasing hormone. These results indicate that both neurotransmitters,
      acetylcholine and luteinizing hormone-releasing hormone, may co-exist in septal
      neurons of the CNS and that they could be modulated by gonadal hormones, and
      suggest that luteinizing hormone-releasing hormone could be involved in some of
      the actions of sex steroids on cholinergic neurotransmission.

PMID- 11301210
TI  - Dopamine transporter-immunoreactive axons in the mediodorsal thalamic nucleus of
      the macaque monkey.
AB  - The reciprocal connections between the mediodorsal thalamic nucleus and the
      prefrontal cortex participate in a circuit that is essential to a number of
      higher cognitive processes. Projections from the dopamine-containing cells of the
      ventral mesencephalon to the prefrontal cortex are also critical for these
      cognitive abilities. It is unclear, however, whether dopamine axons innervate the
      mediodorsal thalamic nucleus in primates. In order to address this question, we
      examined the distribution of dopamine transporter-immunoreactive axons in the
      mediodorsal thalamic nucleus of macaque monkeys. Labeled axons were distributed
      quite heterogeneously in this nucleus, and did not strictly follow
      cytoarchitectonic subdivision boundaries. The ventral and lateral portions of the
      mediodorsal thalamic nucleus, which include parts of the parvicellular and
      multiform subdivisions, had the highest density of dopamine transporter
      immunoreactive axons. In contrast, the dorsomedial portion, which included
      primarily the magnocellular subdivision, had the lowest density of labeled axons.
      In both lightly and densely innervated portions of the nucleus, small, dense
      clusters of dopamine transporter-immunoreactive axons were present. Axons
      immunoreactive for tyrosine hydroxylase were distributed in a pattern very
      similar to that of dopamine transporter-labeled axons. In contrast, noradrenergic
      axons, as revealed by dopamine beta-hydroxylase immunoreactivity, were present in
      higher density and were more evenly distributed throughout the mediodorsal
      thalamic nucleus. This dopamine innervation of the mediodorsal thalamic nucleus
      reveals another possible anatomical substrate through which dopamine may
      influence the cognitive functions mediated by thalamo-prefrontal circuitry.

PMID- 11301211
TI  - Fragile X mice develop sensory hyperreactivity to auditory stimuli.
AB  - Fragile X syndrome is the most prevalent cause of mental retardation. It is
      usually caused by the transcriptional inactivation of the FMR-1 gene. Although
      the cognitive defect is the most recognized symptom of fragile X syndrome,
      patients also show behavioral problems such as hyperarousal, hyperactivity,
      autism, aggression, anxiety and increased sensitivity to sensory stimuli. Here we
      investigated whether fragile X mice (fmr-1 gene knockout mice) exhibit abnormal
      sensitivity to sensory stimuli. First, hyperreactivity of fragile X mice to
      auditory stimulus was indicated in the prepulse inhibition paradigm. A moderately
      intense prepulse tone, that suppresses startle response to a strong auditory
      stimulus, elicited a significantly stronger effect in fragile X than in control
      mice. Second, sensory hyperreactivity of fragile X mice was demonstrated by a
      high seizure susceptibility to auditory stimulation. Selective induction of c
      Fos, an early-immediate gene product, indicated that seizures involve auditory
      brainstem and thalamic nuclei. Audiogenic seizures were not due to a general
      increase in brain excitability because three different chemical convulsants
      (kainic acid, bicuculline and pentylenetetrazole) elicited similar effects in
      fragile X and wild-type mice. These data are consistent with the increased
      responsiveness of fragile X patients to auditory stimuli. The auditory
      hypersensitivity suggests an abnormal processing in the auditory system of
      fragile X mice, which could provide a useful model to study the molecular and
      cellular changes underlying fragile X syndrome.

PMID- 11301212
TI  - GABA B receptor-mediated effects on expression of c-Fos in rat trigeminal nucleus
      following high- and low-intensity afferent stimulation.
AB  - We examined the effects of systemic administration of a GABA(B) receptor agonist,
      baclofen, or antagonist, phaclofen, on the expression of c-Fos protein induced 3h
      after electrical stimulation of the trigeminal ganglion at low (0.1 mA) or high
      intensities (1.0 mA) in the urethane-anesthetized rat. In saline-treated rats, 10
      min stimulation of the trigeminal ganglion induced c-Fos-immunopositive neurons
      throughout the full extent of the ipsilateral superficial layers of the
      trigeminal nucleus caudalis, and dorsal or dorsomedial part of the nuclei rostral
      to obex (trigeminal nucleus principalis, dorsomedial nucleus of trigeminal
      nucleus oralis and dorsomedial nucleus of trigeminal nucleus interpolaris).
      Animals stimulated at 1.0 mA induced a significantly higher number of labeled
      neurons in all the trigeminal sensory nuclei than animals stimulated at 0.1 mA.
      In rats treated with 20mg/kg i.p. baclofen and stimulated at 0.1 mA, the numbers
      of Fos-positive neurons in all the trigeminal sensory nuclei were significantly
      decreased compared to saline-treated controls. After stimulation at 1.0 mA in
      rats treated with baclofen, the numbers of Fos-positive neurons in all the
      trigeminal sensory nuclei were also significantly decreased. In rats treated with
      2mg/kg i.p. phaclofen and stimulated at 1.0 mA, the numbers of Fos-positive
      neurons were significantly increased in all the trigeminal sensory nuclei.
      However, after stimulation at 0.1 mA in rats treated with phaclofen, the numbers
      of Fos-positive neurons were significantly decreased in the superficial layers
      and magnocellular zone of trigeminal nucleus caudalis and dorsomedial nucleus of
      trigeminal nucleus oralis. These results indicate that the expression of c-Fos in
      the trigeminal sensory nucleus is differentially regulated through GABAB
      receptors in a manner that is dependent on the nucleus and the type of primary
      afferents that are activated by different stimulus intensities. Systemic
      administration of baclofen could inhibit both nociceptive and non-nociceptive
      sensory activity in the trigeminal sensory nucleus. Systemic administration of
      phaclofen could enhance nociceptive sensory activity but not non-nociceptive
      activity.

PMID- 11301213
TI  - Long-term changes in the distribution of galanin in dorsal root ganglia after
      sciatic or spinal nerve transection in rats.
AB  - The neuropeptide galanin is upregulated in primary afferent and sympathetic
      neurones and might be involved in the development of sympathetic perineuronal
      baskets ("rings") following nerve injury. Galanin, calcitonin gene-related
      peptide and tyrosine hydroxylase have been examined immunohistochemically in
      dorsal root ganglia and associated roots at times up to one year after
      transection of either sciatic or L5 spinal nerves in adult rats. Small diameter
      somata containing calcitonin gene-related peptide (with or without galanin) were
      reduced in number, whereas galanin (and, at later times, calcitonin gene-related
      peptide) appeared in medium to large diameter cells after both types of lesion.
      Galanin also appeared in axons in grey rami and somata in lumbar paravertebral
      ganglia. Within dorsal root ganglia, galanin-positive axons formed perineuronal
      rings of two types: (i) smooth coiled axons surrounded small (< 30 microm
      diameter) somata from which they probably arose; these were rare after 12 weeks,
      particularly after a spinal nerve lesion; and (ii) varicose terminals encircled
      medium to large galanin-positive somata; some arose from brightly
      immunofluorescent somata nearby and took nearly a year to disappear. About 30% of
      varicose galanin-positive rings had associated calcitonin gene-related peptide
      positive terminals (partly colocalized) whereas nearly 45% had associated
      tyrosine hydroxylase-positive terminals (partly colocalized). Synaptophysin was
      present in swollen axons and in some varicosities of all types. We conclude that,
      after peripheral nerve lesions, varicose perineuronal rings around large diameter
      dorsal root ganglion cells may be formed by axotomized primary afferent neurones
      (some containing calcitonin gene-related peptide) and sympathetic neurones, both
      of which contain upregulated galanin. Exocytosis from the varicosities may modify
      the excitability of mechanosensitive somata. Small galanin-positive somata
      disappear over several months after both lesions as calcitonin gene-related
      peptide reappears in medium to large neurones.

PMID- 11301214
TI  - Met-enkephalin is preferentially transported into the peripheral processes of
      primary afferent fibres in both control and HSV1-driven proenkephalin A
      overexpressing rats.
AB  - The demonstration of preproenkephalin A gene expression in rat dorsal root
      ganglia has raised the question of the physiological role of met-enkephalin
      containing primary afferent fibres. Recently, we showed that systemic infection
      with a recombinant Herpes simplex virus encoding preproenkephalin A (HSVLatEnk1)
      yielded a marked increase in the density of met-enkephalin-like material
      synthesising neurons in rat dorsal root ganglia. This study further investigated
      the synthesis, transport and release of met-enkephalin-like material in the
      central and/or peripheral processes of primary afferent fibres in HSVLatEnk1
      infected and control rats. In controls, dorsal root ganglia neurons containing
      met-enkephalin-like material were scarce and only a few positively labelled
      processes were seen at the peripheral output of the dorsal root ganglia. Met
      enkephalin-like material accumulated at the proximal side of ligatured sciatic
      nerve, but not in ligatured L4-L5 dorsal roots. In HSVLatEnk1-infected rats with
      numerous somas and fibres stained for met-enkephalin-like material in dorsal root
      ganglia, met-enkephalin immunoreactive material largely accumulated at the
      proximal side of the ligatured sciatic nerve and few positively stained fibres
      were also observed in ligatured dorsal roots. Electrical stimulation of L4-L5
      dorsal roots attached to a dorsal slice of the lumbar enlargement produced an
      overflow of met-enkephalin-like material which was approximately 70% higher in
      HSVLatEnk1-infected rats compared to controls. At the periphery, subcutaneous
      microdialysis showed higher basal levels of met-enkephalin-like material in the
      interstitial fluid of hindpaw plantar area in HSVLatEnk1-infected rats, and
      electrical stimulation of the ipsilateral sciatic nerve resulted in an
      approximately three-fold-higher overflow of this material than in control rats.
      These data demonstrated that met-enkephalin synthesised in dorsal root ganglion
      of both control and preproenkephalin A overexpressing rats is preferentially
      transported into the peripheral processes of primary afferent fibres where the
      peptide reaches a releasable compartment, thus providing a neuronal source of
      peripheral met-enkephalin.

PMID- 11301215
TI  - Bi-directional modulation of 5-hydroxytryptamine-induced plasma extravasation in
      the rat knee joint by nociceptin.
AB  - The role of nociceptin, the endogenous ligand for the opioid receptor-like (ORL1)
      receptor, in nociceptive processing is controversial. Most studies demonstrate
      hyperalgesia following supraspinal administration, analgesia following
      intrathecal and peripheral administration at higher doses, and hyperalgesia
      following intrathecal and peripheral application at lower doses. The present
      study investigates the effect of nociceptin on synovial plasma extravasation and
      its ability to modulate 5-hydroxytryptamine-induced synovial plasma extravasation
      using the rat knee joint model of inflammation. Nociceptin alone does not alter
      synovial plasma extravasation from baseline. Nociceptin at concentrations up to 1
      nM enhances 5-hydroxytryptamine-induced synovial plasma extravasation (up to 50%)
      and nociceptin at concentrations above 100 nM inhibits 5-hydroxytryptamine
      induced synovial plasma extravasation (down to 45%). The novel, selective ORL1
      receptor antagonist J-113397 potently inhibits the pro-inflammatory effect of
      nociceptin, but only partly inhibits, at higher concentrations, the anti
      inflammatory effects of nociceptin.These findings demonstrate a dose-dependent bi
      directional effect of nociceptin on inflammatory processes and may indicate a
      target for novel therapeutics.

PMID- 11301216
TI  - Polysialylated neural cell adhesion molecule is involved in the neuroplasticity
      induced by axonal injury in the avian ciliary ganglion.
AB  - We demonstrated previously in the quail ciliary ganglion, that the
      immunoreactivity for the neural cell adhesion molecule labeling the postsynaptic
      specializations of intraganglionic synapses decreases when synaptic remodeling is
      induced by crushing the postganglionic ciliary nerves. Here we show, in the same
      experimental conditions, that the immunolabeling for its polysialylated non
      stabilizing isoform, which promotes cell plasticity, increases at these
      subcellular compartments. In control ganglia, poor immunolabeling for the
      polysialylated neural cell adhesion molecule was occasionally observed
      surrounding the soma of the ciliary neurons, in correspondence with the
      calyciform presynaptic ending and the perineuronal satellite cells sheath. At the
      electron microscope, several neuronal compartments, including some postsynaptic
      specializations, somatic spines and multivesicular bodies, were immunopositive.
      Three to six days after ciliary nerve crush, both the number of ciliary neurons
      labeled for the polysialylated neural cell adhesion molecule and the intensity of
      their immunolabeling increased markedly. Electron microscopy revealed that, in
      parallel to the injury-induced detachment of the preganglionic boutons, numerous
      postsynaptic specializations were found to be immunopositive. Twenty days later,
      when intraganglionic connections were re-established, polysialylated neural cell
      adhesion molecule immunoreactivity was comparable to that observed in control
      ganglia. The increase in immunolabeling also involved the other neuronal
      compartments mentioned above, the perineuronal satellite cells and the
      intercellular space between these and the ciliary neurons. From these results we
      suggest that the switch, at the postsynaptic specializations, between the neural
      cell adhesion molecule and its polysialylated form may be among the molecular
      changes occurring in axotomized neurons leading to injury-induced synaptic
      remodeling. Moreover, from the increase in polysialylated neural cell adhesion
      molecule immunolabeling, observed at the somatic spines and at the interface
      between neurons and perineuronal satellite cells, we suggest that this molecule
      may be involved not only in synaptic remodeling, but also in other more general
      aspects of injury-induced neuronal plasticity.

PMID- 11301217
TI  - Chronic inflammatory demyelinating polyneuropathy in childhood.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) in children is
      relatively rare. However, it has been recognized for many years. In patients
      presenting with this disease, subacute onset of weakness usually develops over at
      least 2 months and often progresses to a loss of ambulation. Some children's
      initial presentations may mimic Guillain-Barre syndrome. Dysasthesias are common.
      Males are affected more than females, and antecedent illnesses or vaccinations
      occur in approximately half of patients. Physical examination reveals diffuse,
      proximal greater than distal weakness, with an absence or depression of muscle
      stretch reflexes. Electrophysiology confirms demyelination, and spinal fluid
      examination demonstrates albuminocytologic dissociation. The clinical
      presentation, diagnosis, and prognosis of childhood CIDP are reviewed. Treatment
      and immunologic features are also discussed in this article.

PMID- 11301218
TI  - Language regression in childhood.
AB  - Language regression is observed both in autistic regression and as part of
      acquired epileptic aphasia (Landau-Kleffner Syndrome). We prospectively
      identified 177 children with language regression at four major medical centers,
      and their clinical characteristics were recorded. Their mean age at regression
      was 22.8 months. The mean time-to-specialist referral was 38 months of age. Most
      children (88%) met criteria for autism or manifested autistic features. Males (P
      = 0.02) and children less than 3 years of age who regressed (P = 0.016) had a
      higher probability of developing autistic behaviors. Seizures were more common in
      children who regressed after they reached 3 years of age (P < 0.001), and
      children with seizures were less likely to have associated autistic regression (P
      < 0.001). Electroencephalogram abnormalities were reported in 37% of patients and
      were more common in children with seizures (P < 0.001). At last follow-up,
      language function was impaired in 88% of the children, although some improvement
      was noted in 57%. We conclude that the loss of previously acquired language at
      any age, even if that language only includes a few words or communicative
      gestures, is often associated with a more global regression in cognition and/or
      behavior and has serious implications for future function. Early identification
      and referral of these children is necessary to allow for diagnosis and
      intervention.

PMID- 11301219
TI  - Carbamyl phosphate synthetase 1 deficiency: a destructive encephalopathy.
AB  - Carbamyl phosphate synthetase I is a urea cycle enzyme. Severe deficiency of
      carbamyl phosphate synthetase I presents in the neonatal period as hyperammonemic
      encephalopathy with altered consciousness and occasional seizures after feeding
      begins. Episodes of altered consciousness with or without seizures and focal
      neurologic deficits are seen later with patients of partial carbamyl phosphate
      synthetase I deficiency. Fatal cerebral edema with brain herniation may develop
      on occasion. Three patients presenting with carbamyl phosphate synthetase I
      deficiency are reported with neuroimaging and pathologic findings illustrating
      the destructive encephalopathy with acute cerebral edema, followed by diffuse
      cerebral atrophy and occasional cystic encephalomalacia. The deterioration in
      carbamyl phosphate synthetase I deficiency occurs during the hyperammonemic
      crises. This deficiency may be difficult to treat despite the current advances in
      treatment strategies, especially in neonatal-onset patients with low carbamyl
      phosphate synthetase I activity.

PMID- 11301220
TI  - Ocular motor dysfunction in Lesch-Nyhan disease.
AB  - Eye movements were assessed in 22 patients with varying degrees of hypoxanthine
      guanine phosphoribosyltransferase deficiency. Ocular motility was clinically
      normal in seven patients with moderate enzyme deficiency but grossly abnormal in
      15 patients with severe enzyme deficiency. In patients with severe deficiency,
      fixation was interrupted by frequent unwanted saccades toward minor visual
      distractions. Voluntary saccades were associated with an initial head movement
      and/or eyeblink in all of these patients. When head motion was prevented,
      voluntary saccades were often delayed and sometimes absent. In contrast, saccade
      speed, reflexive saccades, and other reflexive eye movements appeared clinically
      normal. Four patients with severe enzyme deficiency also experienced mild
      blepharospasm, and two had ocular tics. These disturbances of ocular motility are
      consistent with dysfunction of the basal ganglia or its connections with ocular
      motor centers in the prefrontal cortex or midbrain.

PMID- 11301221
TI  - Brainstem auditory-evoked potentials in iron-deficiency anemia.
AB  - Slight-to-moderate impairments may be observed in mental and motor developments
      of infants with iron- deficiency anemia. Brainstem auditory-evoked potentials
      provide a noninvasive means of examining the auditory aspect of the central
      nervous system functions. In this study the effect of iron-deficiency anemia on
      auditory functions was investigated by using brainstem auditory-evoked
      potentials. Brainstem auditory-evoked potentials of the 20 iron-deficient infants
      were not significantly different from those of the control group that included 20
      healthy age-matched infants. Furthermore, there was not a statistically
      significant difference between the brainstem auditory-evoked potentials of the
      study group performed before and 3 months after oral iron therapy. Although we
      could not demonstrate a hearing loss in infants with moderate iron-deficiency
      anemia in this study, the relationship between severe iron-deficiency anemia and
      hearing loss or auditory dysfunction remains to be determined.

PMID- 11301222
TI  - Predictors and underlying causes of medically intractable localization-related
      epilepsy in childhood.
AB  - The goal of this study is to clarify the prognostic factors in childhood
      localization-related epilepsy in a tertiary medical center. Children (n = 113)
      with symptomatic and cryptogenic localization-related epilepsy were divided into
      groups of intractable patients (average seizure frequency: one or more per month
      during the 6 months before the last follow-up; n = 40) and well-controlled
      patients (no seizures for at least 1 year before the last follow-up; n = 73).
      Clinical and electroencephalogram (EEG) factors were examined to elucidate
      prognostic factors. The subtypes of epilepsies and causes were also investigated.
      Univariate analyses indicated that the following factors were correlated with
      seizure outcome: (1) seizure type at the first visit; (2) seizure frequency; (3)
      underlying cause; (4) age at onset of epilepsy; (5) status epilepticus occurring
      as the first seizure and before the first visit; and (6) diffuse epileptic
      discharges on first visit interictal EEGs. Multivariate analyses revealed that
      seizure type at the first visit, seizure frequency, status epilepticus before the
      first visit, and underlying causes were significant independent predictive
      factors. The rate of intractable patients was highest in multilobar epilepsy,
      followed by frontal-lobe epilepsy. Regarding etiologies, the intractable group
      contained nine patients with encephalitis of unknown origin and three each with
      localized cortical malformation and mesial temporal sclerosis.

PMID- 11301223
TI  - Do antiepileptic drugs differ in suppressing interictal epileptiform activity in
      children?
AB  - Antiepileptic drugs may suppress interictal epileptiform activity in addition to
      suppressing seizures, although the comparative rates of suppression of interictal
      epileptiform activity for phenobarbital (PHB), carbamazepine (CBZ), and valproate
      (VPA) in children are unknown. Electroencephalogram (EEG) pairs were identified
      in which the first tracing illustrated interictal epileptiform activity before
      antiepileptic drug treatment; the rate of clearance of such activity in the
      subsequent tracing was assessed according to the drug introduced. EEG pairs (n =
      213) were identified for CBZ, PHB, and VPA. Overall suppression rates of
      epileptiform activity in the second EEG were 12/55 (22%) for PHB, 27/81 (33%) for
      CBZ, and 35/77 (46%) for VPA (P = 0.005 for VPA vs PHB). When suppression rates
      were assessed comparing sleep-state pairs, suppression rates were 24/80 (30%) for
      PHB, 51/129 (40%) for CBZ, and 60/120 (50%) for VPA (P = 0.005 for PHB vs VPA). A
      subanalysis for focal discharges yielded suppression rates of 10/43 (23%) for
      PHB, 19/60 (32%) for CBZ, and 8/19 (42%) for VPA; for generalized discharges,
      2/12 (17%) for PHB, 8/21 (38%) for CBZ, and 27/58 (47%) for VPA. VPA, and to a
      lesser extent CBZ, appeared superior to PHB in suppressing interictal
      epileptiform activity, including both focal and generalized epileptiform
      activity.

PMID- 11301224
TI  - Fosphenytoin in infants of extremely low birth weight.
AB  - Fosphenytoin, a phosphorylated prodrug of phenytoin, is useful for acute
      seizures, is given by parenteral administration, and has few cardiac and local
      irritation adverse effects. There is limited experience in the administration of
      this new agent to newborns, and concern has been raised regarding the conversion
      of the prodrug to phenytoin. In two low--birth-weight infants, it was observed
      that fosphenytoin was converted adequately with varying effects on seizure
      control.

PMID- 11301225
TI  - Congenital CMV with callosal lipoma and agenesis.
AB  - An infant with symptomatic congenital Cytomegalovirus infection is reported.
      After the detection of abnormalities on cranial ultrasound scanning, magnetic
      resonance imaging of the brain revealed a complete absence of corpus callosum
      with a midline anterior tubulonodular lipoma. A proposed causative link between
      early in utero Cytomegalovirus infection and lipoma with agenesis of corpus
      callosum is discussed.

PMID- 11301226
TI  - Ictal (99m)Tc ECD SPECT in paroxysmal kinesigenic choreoathetosis.
AB  - Paroxysmal kinesigenic choreoathetosis is a rare neurologic disorder
      characterized by sudden attacks of brief involuntary dyskinetic movement that are
      precipitated by voluntary movement. A 14-year-old male who presented with
      frequent brief attacks of hemidystonia triggered by sudden movement is reported.
      Investigations, including video electroencephalogram and magnetic resonance
      imaging of brain, were normal. There was excellent and sustained response to
      carbamazepine. Ictal single-photon emission computed tomography using (99m)Tc
      ethyl cysteinate dimer revealed increased perfusion of the contralateral basal
      ganglia, which is associated with onset of choreoathetosis attacks. Our findings
      provide evidence that hyperactivity of the basal ganglia is associated with the
      dyskinetic attacks in paroxysmal kinesigenic choreoathetosis.

PMID- 11301227
TI  - IFAP syndrome "plus" seizures, mental retardation, and callosal hypoplasia.
AB  - Ichthyosis follicularis, congenital alopecia, and photophobia are typical
      features of a rare X-linked recessive disorder termed ichthyosis follicularis
      with atrichia and photophobia syndrome. A 3-year-old male with these findings and
      severe growth failure, mental retardation, generalized seizures, vascularizing
      keratitis, nail anomalies, inguinal hernia, and a normal chromosome constitution
      is presented. Two maternal male relatives were affected by the same condition.
      Magnetic resonance imaging revealed corpus callosum hypoplasia not described at
      present. Syndromes with alopecia, seizures, and mental retardation are analyzed
      on the basis of genetic and clinical results.

PMID- 11301228
TI  - Ocular dominance in anterior visual cortex in a child demonstrated by the use of
      fMRI.
AB  - Negative signal changes in the visual cortex have been observed during visual
      stimulation when performing functional magnetic resonance imaging (fMRI) in
      children. This report investigated whether the ocular dominance, which has been
      demonstrated in the contralateral anterior visual cortex in adults, could be
      observed in a child by the use of fMRI. A 5-year-old child was studied using fMRI
      at 1.5 T during alternating monocular visual stimulation under sedation with
      morphine and pentobarbital. The functional images were motion corrected, and
      statistical parametric maps were made by contrasting the left or right eye
      stimulation conditions vs the right or left eye stimulation conditions,
      respectively, at each voxel. Areas with negative signal changes were found on the
      left anterior visual cortex during monocular visual stimulation of the right eye
      and vice versa. There was no area with negative or positive signal change on the
      ipsilateral visual cortex to the stimulated eye and no area with positive signal
      change on the contralateral visual cortex. Contralateral ocular dominance of
      anterior visual cortex similar to that of adults was demonstrated in this child
      with a negative correlation with the visual stimulus. This finding suggests that
      peripheral visual fields are represented in the anterior visual cortex of 5-year
      old children.

PMID- 11301230
TI  - Cerebral vascular events associated with ulcerative colitis in children.
AB  - Although peripheral vascular thrombic events are recognized as a serious extra
      intestinal complication of inflammatory bowel disease, the occurrence of cerebral
      vascular events in association with acute exacerbations of this group of diseases
      is rare. In this article, relevant literature is reviewed and three children, 5,
      12, and 13 years of age, who presented with clinical and magnetic resonance
      imaging evidence of an acute cerebrovascular event in association with an acute
      exacerbation of their inflammatory bowel disease are described. Except for the
      presence of anemia, hematologic and coagulation studies were unremarkable, and a
      search for evidence of a systemic vasculitis proved negative.

PMID- 11301229
TI  - Limb girdle muscular dystrophy type 2A presenting with cardiac arrest.
AB  - The occurrence of respiratory failure in progressive neuromuscular disorders is
      well recognized. This failure is observed most commonly in Duchenne dystrophy but
      sometimes occurs in Becker's, limb-girdle, and facioscapulohumeral dystrophies.
      Patients usually present acutely or subacutely with cyanosis and cor pulmonale,
      with severe decompensation often being precipitated by an acute intercurrent
      infection. However, cardiopulmonary arrest is an uncommon presentation. A male
      diagnosed with limb-girdle muscular dystrophy type 2A who presented with
      cardiopulmonary arrest that was precipitated by an upper respiratory tract
      infection is presented. The nocturnal application of noninvasive intermittent
      positive pressure ventilation with a bilevel positive airway pressure (Bi-PAP)
      device improved his symptoms and quality of life without resorting to more
      invasive and more-restrictive forms of support. This report demonstrates an
      unusual presentation of limb-girdle muscular dystrophy and documents that
      nocturnal nasal administration of continuous airway pressure using the Bi-PAP
      device may be sufficient to maintain adequate ventilation in such patients.

PMID- 11301232
TI  - Cognitive neuroscience at the turn of the millennium [correction of millenium].

PMID- 11301233
TI  - Neuroimaging of visual awareness in patients and normal subjects.
AB  - The immediacy and directness of our visual experience belies the complexity of
      the underlying neural mechanisms, which remain incompletely understood. Recent
      neuroimaging studies suggest that activity in ventral visual cortex is necessary
      but not sufficient for visual awareness. Experiments in both patients and normal
      subjects indicate that parietal and frontal areas make an important contribution
      to visual awareness, suggesting that reciprocal interactions between dorsal
      frontoparietal areas and ventral visual cortex may provide a fundamental neural
      substrate for conscious visual experience.

PMID- 11301234
TI  - Neuroimaging of cognitive functions in human parietal cortex.
AB  - Functional neuroimaging has proven highly valuable in mapping human sensory
      regions, particularly visual areas in occipital cortex. Recent evidence suggests
      that human parietal cortex may also consist of numerous specialized subregions
      similar to those reported in neurophysiological studies of non-human primates.
      However, parietal activation generalizes across a wide variety of cognitive tasks
      and the extension of human brain mapping into higher-order "association cortex"
      may prove to be a challenge.

PMID- 11301235
TI  - Behavioral planning in the prefrontal cortex.
AB  - Recent studies have presented evidence that the prefrontal cortex plays a crucial
      role in every aspect of the cognitive processes necessary for behavioral
      planning: processing and integration of perceived or memorized information,
      associative learning, reward-based behavioral control, behavioral
      selection/decision-making and behavioral guidance. We propose that the creation
      of novel information is the means by which the prefrontal cortex operates to
      achieve executive control over behavioral planning. The prefrontal cortex is the
      site of operation of nodal points, where neural circuits integrate currently
      available or memorized information to generate the information that is necessary
      to perform an action. The prefrontal cortex also regulates the flow of
      information through multiple nodes to meet behavioral demands.

PMID- 11301236
TI  - Object-based vision and attention in primates.
AB  - In forming a representation of a visible object, the brain must analyze the
      visual scene pre-attentively, select an object through active attention, and form
      representations of the multiple attributes of the selected object. During the
      past two years, progress has been made in understanding the neural underpinnings
      of these processes by means of single-neuron recording in monkeys.

PMID- 11301237
TI  - Molecular mechanisms of memory acquisition, consolidation and retrieval.
AB  - Memory is often considered to be a process that has several stages, including
      acquisition, consolidation and retrieval. Memory can be modified further through
      reconsolidation and performance can change during extinction trials while the
      original memory remains intact. Recent studies of the molecular basis of these
      processes have found that many signaling molecules are involved in several stages
      of memory but, in some cases, molecular pathways may be selectively recruited
      only during certain stages of memory.

PMID- 11301238
TI  - Role of perirhinal cortex in object perception, memory, and associations.
AB  - The perirhinal cortex plays a key role in acquiring knowledge about objects. It
      contributes to at least four cognitive functions, and recent findings provide new
      insights into how the perirhinal cortex contributes to each: first, it
      contributes to recognition memory in an automatic fashion; second, it probably
      contributes to perception as well as memory; third, it helps identify objects by
      associating together the different sensory features of an object; and fourth, it
      associates objects with other objects and with abstractions.

PMID- 11301239
TI  - Semantic memory and the brain: structure and processes.
AB  - Recent functional brain imaging studies suggest that object concepts may be
      represented, in part, by distributed networks of discrete cortical regions that
      parallel the organization of sensory and motor systems. In addition, different
      regions of the left lateral prefrontal cortex, and perhaps anterior temporal
      cortex, may have distinct roles in retrieving, maintaining and selecting semantic
      information.

PMID- 11301240
TI  - Spatiotemporal mapping of brain activity by integration of multiple imaging
      modalities.
AB  - Functional magnetic resonance imaging (fMRI) and positron emission tomography
      measure local changes in brain hemodynamics induced by cognitive or perceptual
      tasks. These measures have a uniformly high spatial resolution of millimeters or
      less, but poor temporal resolution (about 1s). Conversely, electroencephalography
      (EEG) and magnetoencephalography (MEG) measure instantaneously the current flows
      induced by synaptic activity, but the accurate localization of these current
      flows based on EEG and MEG data alone remains an unsolved problem. Recently,
      techniques have been developed that, in the context of brain anatomy visualized
      with structural MRI, use both hemodynamic and electromagnetic measures to arrive
      at estimates of brain activation with high spatial and temporal resolution. These
      methods range from simple juxtaposition to simultaneous integrated techniques.
      Their application has already led to advances in our understanding of the neural
      bases of perception, attention, memory and language. Further advances in multi
      modality integration will require an improved understanding of the coupling
      between the physiological phenomena underlying the different signal modalities.

PMID- 11301241
TI  - Spatial localization and resolution of BOLD fMRI.
AB  - It has been demonstrated that the blood-oxygenation-level-dependent (BOLD) fMRI
      initial dip allows us to resolve (without differential subtraction) structures of
      the order of 0.5 mm. However, recent results support the proposition that even
      the later, positive BOLD fMRI signal component can allow us to resolve structures
      less than 1 mm in size by using differential subtraction when the signal-to-noise
      ratio is high. So, with a sufficient signal-to-noise ratio, the later, positive
      component should be useable as a probe for testing cognitive neuroscientific
      hypotheses that predict neuroanatomical dissociations of less than 1mm.

PMID- 11301242
TI  - Cognitive and perceptual development during infancy.
AB  - Over the past seven years, the main advances in our understanding of infant
      development have involved the application of cognitive neuroscience methods such
      as neuroimaging and computer modelling. Results obtained using these methods have
      illuminated further the complex interactions between nature and nurture that
      underlie early postnatal development.

PMID- 11301243
TI  - The development of face expertise.
AB  - Recent neuroimaging studies in adults indicate that visual areas selective for
      recognition of faces can be recruited through expertise for nonface objects. This
      reflects a new emphasis on experience in theories of visual specialization. In
      addition, novel work infers differences between categories of nonface objects,
      allowing a re-interpretation of differences seen between recognition of faces and
      objects. Whether there are experience-independent precursors of face expertise
      remains unclear; indeed, parallels between literature for infants and adults
      suggest that methodological issues need to be addressed before strong conclusions
      can be drawn regarding the origins of face recognition.

PMID- 11301244
TI  - Evolutionary psychology and the brain.
AB  - The human brain is a set of computational machines, each of which was designed by
      natural selection to solve adaptive problems faced by our hunter-gatherer
      ancestors. These machines are adaptive specializations: systems equipped with
      design features that are organized such that they solve an ancestral problem
      reliably, economically and efficiently. The search for functionally specialized
      computational adaptations has now begun in earnest. A host of specialized systems
      have recently been found, including ones designed for sexual motivation, social
      inference, judgment under uncertainty and conditioning, as well as content-rich
      systems for visual recognition and knowledge acquisition.

PMID- 11301245
TI  - The neurobiology of social cognition.
AB  - Recent studies have begun to elucidate the roles played in social cognition by
      specific neural structures, genes, and neurotransmitter systems. Cortical regions
      in the temporal lobe participate in perceiving socially relevant stimuli, whereas
      the amygdala, right somatosensory cortices, orbitofrontal cortices, and cingulate
      cortices all participate in linking perception of such stimuli to motivation,
      emotion, and cognition. Open questions remain about the domain-specificity of
      social cognition, about its overlap with emotion and with communication, and
      about the methods best suited for its investigation.

PMID- 11301246
TI  - Neuroimaging and neuropathological studies of depression: implications for the
      cognitive-emotional features of mood disorders.
AB  - Neuroimaging technology has provided unprecedented opportunities for elucidating
      the anatomical correlates of major depression. The knowledge gained from imaging
      research and from the postmortem studies that have been guided by imaging data is
      catalyzing a paradigm shift in which primary mood disorders are conceptualized as
      illnesses that involve abnormalities of brain structure, as well as of brain
      function. These data suggest specific hypotheses regarding the neural mechanisms
      underlying pathological emotional processing in mood disorders. They particularly
      support a role for dysfunction within the prefrontal cortical and striatal
      systems that normally modulate limbic and brainstem structures involved in
      mediating emotional behavior in the pathogenesis of depressive symptoms.

PMID- 11301247
TI  - Investigating the neurocognitive deficits associated with chronic drug misuse.
AB  - Cognitive deficits associated with the chronic abuse of drugs have important
      theoretical and clinical significance: such deficits reflect changes to the
      underlying cortical, sub-cortical and neuromodulatory mechanisms that underpin
      cognition, and also interfere directly with rehabilitative programs. Recent
      investigations have been made into the neuropsychology of chronic abuse of
      cannabis, stimulants and opiates. It is suggested that future progress in this
      area, involving developing advances in brain-imaging and neuropharmacology, will
      capitalize on experimental demonstrations of specific patterns of impairments in
      decision-making, attention and memory function.

PMID- 11301248
TI  - Notch signaling targets the Wingless responsiveness of a Ubx visceral mesoderm
      enhancer in Drosophila.
AB  - BACKGROUND: Members of the Notch family of receptors mediate a process known as
      lateral inhibition that plays a prominent role in the suppression of cell fates
      during development. This function is triggered by a ligand, Delta, and is
      implemented by the release of the intracellular domain of Notch from the membrane
      and by its interaction with the protein Suppressor of Hairless [Su(H)] in the
      nucleus. There is evidence that Notch can also signal independently of Su(H). In
      particular, in Drosophila, there is evidence that a Su(H)-independent activity of
      Notch is associated with Wingless signaling. RESULTS: We report that Ubx(VM)B, a
      visceral mesoderm-specific enhancer of the Ubx gene of Drosophila, is sensitive
      to Notch signaling. In the absence of Notch, but not of Su(H), the enhancer
      becomes activated earlier and over a wider domain than in the wild type.
      Furthermore, the removal of Notch reduces the requirement for Disheveled-mediated
      Wingless signaling to activate this enhancer. This response to Notch is likely to
      be mediated by the dTcf binding sites in the Ubx(VM)B enhancer. CONCLUSIONS: Our
      results show that, in Drosophila, an activity of Notch that is likely to be
      independent of Su(H) inhibits Wingless signaling on Ubx(VM)B. A possible target
      of this activity is dTcf. As dTcf has been shown to be capable of repressing
      Wingless targets, our results suggest that this repressive activity may be
      regulated by Notch. Finally, we suggest that Wingless signaling is composed of
      two steps, a down-regulation of a Su(H)-independent Notch activity that modulates
      the activity of dTcf and a canonical Wingless signaling event that regulates the
      activity of Armadillo and its interaction with dTcf.

PMID- 11301249
TI  - A novel pathway of cellular phosphatidylinositol(3,4,5)-trisphosphate synthesis
      is regulated by oxidative stress.
AB  - BACKGROUND: Phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] is a key
      second messenger found ubiquitously in higher eukaryotic cells. The activation of
      Class I phosphoinositide 3-kinases and the subsequent production of
      PtdIns(3,4,5)P(3) is an important cell signaling event that has been causally
      linked to the activation of a variety of downstream cellular processes, such as
      cell migration and proliferation. Although numerous proteins regulating a variety
      of biological pathways have been shown to bind PtdIns(3,4,5)P(3), there are no
      data to demonstrate multiple mechanisms for PtdIns(3,4,5)P(3) synthesis in vivo.
      RESULTS: In this study, we demonstrate an alternative pathway for the in vivo
      production of PtdIns(3,4,5)P(3) mediated by the action of murine Type Ialpha
      phosphatidylinositol 4-phosphate 5-kinase (Type Ialpha PIPkinase), an enzyme best
      characterized as regulating cellular PtdIns(4,5)P(2) levels. Analysis of this
      novel pathway of PtdIns(3,4,5)P(3) synthesis in cellular membranes leads us to
      conclude that in vivo, Type Ialpha PIPkinase also acts as a PtdIns(3,4)P(2) 5
      kinase. We demonstrate for the first time that cells actually contain an
      endogenous PtdIns(3,4)P(2) 5-kinase, and that during oxidative stress, this
      enzyme is responsible for PtdIns(3,4,5)P(3) synthesis. Furthermore, we
      demonstrate that by upregulating the H(2)O(2)-induced PtdIns(3,4,5)P(3) levels
      using overexpression studies, the endogenous PtdIns(3,4)P(2) 5-kinase is likely
      to be Type Ialpha PIPkinase. CONCLUSIONS: We describe for the first time a novel
      in vivo activity for Type Ialpha PIPkinase, and a novel pathway for the in vivo
      synthesis of functional PtdIns(3,4,5)P(3), a key lipid second messenger
      regulating a number of diverse cellular processes.

PMID- 11301250
TI  - A primary role for the epidermal growth factor receptor in ommatidial spacing in
      the Drosophila eye.
AB  - BACKGROUND: The differentiation of regularly spaced structures within an
      epithelium is a common feature of developmental pattern formation. The regular
      spacing of ommatidia in the Drosophila eye imaginal disc provides a good model
      for this phenomenon. The correct spacing of ommatidia is a central event in
      establishing the precise hexagonal pattern of ommatidia in the Drosophila
      compound eye. The R8 photoreceptors are the founder cells of each of the
      ommatidia that comprise the adult eye and are specified by a bHLH transcription
      factor, Atonal. RESULTS: We find that the epidermal growth factor receptor (Egfr)
      has a primary function in regulating R8 spacing. The receptor's activation within
      nascent ommatidia induces the expression of a secreted inhibitor that blocks
      atonal expression, and therefore ommatidial initiation, in nearby cells. The
      identity of the secreted inhibitor remains elusive but, contrary to previous
      suggestions, we show that it is not Argos. This Egfr-dependent inhibition acts in
      parallel to the inhibition of atonal by the secreted protein Scabrous. The
      activation of the Egfr pathway is dependent on Atonal function via the expression
      of Rhomboid-1. Our results also allow us to conclude that Egfr's role in
      promoting cell survival is largely independent of its role in photoreceptor
      recruitment; even when cell death is blocked, most photoreceptors fail to form.
      CONCLUSIONS: Based on our data and those of others, we propose a model for R8
      spacing that comprises a self-organizing network of signaling molecules. This
      model describes how successive rows of ommatidia form out of phase with each
      other, leading to the hexagonal array of facets in the compound eye.

PMID- 11301251
TI  - Regulation of Xenopus oocyte meiosis arrest by G protein betagamma subunits.
AB  - BACKGROUND: Progesterone induces the resumption of meiosis (maturation) in
      Xenopus oocytes through a nongenomic mechanism involving inhibition of an oocyte
      adenylyl cyclase and reduction of intracellular cAMP. However, progesterone
      action in Xenopus oocytes is not blocked by pertussis toxin, and this finding
      indicates that the inhibition of the oocyte adenylyl cyclase is not mediated by
      the alpha subunits of classical G(i)-type G proteins. RESULTS: To investigate the
      possibility that G protein betagamma subunits, rather than alpha subunits, play a
      key role in regulating oocyte maturation, we have employed two structurally
      distinct G protein betagamma scavengers (G(t)alpha and betaARK-C(CAAX)) to
      sequester free Gbetagamma dimers. We demonstrated that the injection of mRNA
      encoding either of these Gbetagamma scavengers induced oocyte maturation. The
      Gbetagamma scavengers bound an endogenous, membrane-associated Gbeta subunit,
      indistinguishable from Xenopus Gbeta1 derived from mRNA injection. The injection
      of Xenopus Gbeta1 mRNA, together with bovine Ggamma2 mRNA, elevated oocyte cAMP
      levels and inhibited progesterone-induced oocyte maturation. CONCLUSION: An
      endogenous G protein betagamma dimer, likely including Xenopus Gbeta1, is
      responsible for maintaining oocyte meiosis arrest. Resumption of meiosis is
      induced by Gbetagamma scavengers in vitro or, naturally, by progesterone via a
      mechanism that suppresses the release of Gbetagamma.

PMID- 11301252
TI  - A gain-of-function screen for genes controlling motor axon guidance and
      synaptogenesis in Drosophila.
AB  - BACKGROUND: The neuromuscular system of the Drosophila larva contains a small
      number of identified motor neurons that make genetically defined synaptic
      connections with muscle fibers. We drove high-level expression of genes in these
      motor neurons by crossing 2293 GAL4-driven EP element lines with known insertion
      site sequences to lines containing a pan-neuronal GAL4 source and UAS-green
      fluorescent protein elements. This allowed visualization of every synapse in the
      neuromuscular system in live larvae. RESULTS: We identified 114 EPs that generate
      axon guidance and/or synaptogenesis phenotypes in F1 EP x driver larvae. Analysis
      of genomic regions adjacent to these EPs defined 76 genes that exhibit
      neuromuscular gain-of-function phenotypes. Forty-one of these (known genes) have
      published mutant alleles; the other 35 (new genes) have not yet been
      characterized genetically. To assess the roles of the known genes, we surveyed
      published data on their phenotypes and expression patterns. We also examined loss
      of-function mutants ourselves, identifying new guidance and synaptogenesis
      phenotypes for eight genes. At least three quarters of the known genes are
      important for nervous system development and/or function in wild-type flies.
      CONCLUSIONS: Known genes, new genes, and a set of previously analyzed genes with
      phenotypes in the Adh region display similar patterns of homology to sequences in
      other species and have equivalent EST representations. We infer from these
      results that most new genes will also have nervous system loss-of-function
      phenotypes. The proteins encoded by the 76 identified genes include GTPase
      regulators, vesicle trafficking proteins, kinases, and RNA binding proteins.

PMID- 11301253
TI  - Recombination in Wolbachia.
AB  - Wolbachia are widely distributed intracellular bacteria that cause a number of
      reproductive alterations in their eukaryotic hosts. Such alterations include the
      induction of parthenogenesis, feminization, cytoplasmic incompatibility, and male
      killing [1-11]. These important bacteria may play a role in rapid speciation in
      insects [12-14], and there is growing interest in their potential uses as tools
      for biological control and genetic manipulation of pests and disease vectors [15
      16]. Here, we show recombination in the Wolbachia outer surface protein gene
      (wsp) between strains of Wolbachia. In addition, we find a possible ecological
      context for this recombination. Evidence indicates either genetic exchange
      between Wolbachia in a parasitoid wasp and in the fly that it parasitizes or
      horizontal transfer of Wolbachia between the parasitoid and the fly, followed by
      a recombination event. Results have important implications for the evolution of
      these bacteria and the potential use of Wolbachia in biological control.

PMID- 11301254
TI  - Transcriptional and posttranscriptional gene silencing are mechanistically
      related.
AB  - Two distinct gene-silencing phenomena are observed in plants: transcriptional
      gene silencing (TGS), which involves decreased RNA synthesis because of promoter
      methylation, and posttranscriptional gene silencing (PTGS), which involves
      sequence-specific RNA degradation. PTGS is induced by deliberate [1-4] or
      fortuitous production (R.v.B., unpublished data) of double-stranded RNA (dsRNA).
      TGS could be the result of DNA pairing [5], but could also be the result of
      dsRNA, as was shown by the dsRNA-induced inactivation of a transgenic promoter
      [6]. Here, we show that when targeting flower pigmentation genes in Petunia,
      transgenes expressing dsRNA can induce PTGS when coding sequences are used and
      TGS when promoter sequences are taken. For both types of silencing, small RNA
      species are found, which are thought to be dsRNA decay products [7] and determine
      the sequence specificity of the silencing process [8, 9]. Furthermore, silencing
      is accompanied by the methylation of DNA sequences that are homologous to dsRNA.
      DNA methylation is assumed to be essential for regulating TGS and important for
      reinforcing PTGS [10]. Therefore, we conclude that TGS and PTGS are
      mechanistically related. In addition, we show that dsRNA-induced TGS provides an
      efficient tool to generate gene knockouts, because not only does the TGS of a
      PTGS-inducing transgene fully revert the PTGS phenotype, but also an endogenous
      gene can be transcriptionally silenced by dsRNA corresponding to its promoter.

PMID- 11301255
TI  - Late mitotic failure in mice lacking Sak, a polo-like kinase.
AB  - Polo-like kinases in yeast, flies, and mammals regulate key events in mitosis.
      Such events include spindle formation at G2/M, the anaphase-promoting complex
      (APC) at the exit from mitosis, the cleavage structure at cytokinesis, and DNA
      damage checkpoints in G2/M. Polo-like kinases are distinguished by two C-terminal
      polo box (pb) motifs, which localize the enzymes to mitotic structures. We
      previously identified Sak, a novel polo-like kinase found in Drosophila and
      mammals. Here, we demonstrate that the Sak kinase has a functional pb domain that
      localizes the enzyme to the nucleolus during G2, to the centrosomes in G2/M, and
      to the cleavage furrow during cytokinesis. To study the role of Sak in embryo
      development, we generated a Sak null allele, the first polo-like kinase to be
      mutated in mice. Sak(-/-) embryos arrested after gastrulation at E7.5, with a
      marked increase in mitotic and apoptotic cells. Sak(-/-) embryos displayed cells
      in late anaphase or telophase that continued to express cyclin B1 and
      phosphorylated histone H3. Our results suggest that Sak is required for the APC
      dependent destruction of cyclin B1 and for exit from mitosis in the
      postgastrulation embryo.

PMID- 11301256
TI  - Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi,
      inhibits class II MHC-restricted antigen processing.
AB  - While interference with the class I MHC pathway by pathogen-encoded gene
      products, especially those of viruses, has been well documented, few examples of
      specific interference with the MHC class II pathway have been reported. Potential
      targets for such interference are the proteases that remove the invariant chain
      chaperone and generate antigenic peptides. Indeed, recent studies indicate that
      immature dendritic cells express cystatin C to modulate cysteine protease
      activity and the expression of class II MHC molecules [1]. Here, we show that Bm
      CPI-2, a recently discovered cystatin homolog produced by the filarial nematode
      parasite Brugia malayi (W. F. Gregory et al., submitted), inhibits multiple
      cysteine protease activities found in the endosomes/lysosomes of human B
      lymphocyte lines. CPI-2 blocked the hydrolysis of synthetic substrates favored by
      two different families of lysosomal cysteine proteases and blocked the in vitro
      processing of the tetanus toxin antigen by purified lysosome fractions. Moreover,
      CPI-2 substantially inhibited the presentation of selected T cell epitopes from
      tetanus toxin by living antigen-presenting cells. Our studies provide the first
      example of a product from a eukaryotic parasite that can directly interfere with
      antigen presentation, which, in turn, may suggest how filarial parasites might
      inactivate the host immune response to a helminth invader.

PMID- 11301257
TI  - Archaeal primase: bridging the gap between RNA and DNA polymerases.
AB  - In the evolution of life, DNA replication is a fundamental process, by which
      species transfer their genetic information to their offspring. DNA polymerases,
      including bacterial and eukaryotic replicases, are incapable of de novo DNA
      synthesis. DNA primases are required for this function, which is sine qua non to
      DNA replication. In Escherichia coli, the DNA primase (DnaG) exists as a monomer
      and synthesizes a short RNA primer. In Eukarya, however, the primase activity
      resides within the DNA polymerase alpha-primase complex (Pol alpha-pri) on the
      p48 subunit, which synthesizes the short RNA segment of a hybrid RNA-DNA primer.
      To date, very little information is available regarding the priming of DNA
      replication in organisms in Archaea. Available sequenced genomes indicate that
      the archaeal DNA primase is a homolog of the eukaryotic p48 subunit. Here, we
      report investigations of a p48-like DNA primase from Pyrococcus furiosus, a
      hyperthermophilic euryarchaeote. P. furiosus p48-like protein (Pfup41), unlike
      hitherto-reported primases, does not catalyze by itself the synthesis of short
      RNA primers but preferentially utilizes deoxynucleotides to synthesize DNA
      fragments up to several kilobases in length. Pfup41 is the first DNA polymerase
      that does not require primers for the synthesis of long DNA strands.

PMID- 11301258
TI  - An autosomal recessive polycystic kidney disease gene homolog is involved in
      intraflagellar transport in C. elegans ciliated sensory neurons.
AB  - In this report, we show that the Caenorhabditis elegans gene osm-5 is homologous
      to the Chlamydomonas gene IFT88 and the mouse autosomal recessive polycystic
      kidney disease (ARPKD) gene, Tg737. The function of this ARPKD gene may be
      evolutionarily conserved: mutations result in defective ciliogenesis in worms
      [1], algae [2], and mice [2, 3]. Intraflagellar transport (IFT) is essential for
      the development and maintenance of motile and sensory cilia [4]. The
      biochemically isolated IFT particle from Chlamydomonas flagella is composed of 16
      polypeptides in one of two Complexes (A and B) [5, 6] whose movement is powered
      by kinesin II (anterograde) and cytoplasmic dynein (retrograde) [7-9]. We
      demonstrate that OSM-5 (a Complex B polypeptide), DAF-10 and CHE-11 (two Complex
      A polypeptides), and CHE-2 [10], a previously uncategorized IFT polypeptide, all
      move at the same rate in C. elegans sensory cilia. In the absence of osm-5, the
      C. elegans autosomal dominant PKD (ADPKD) gene products [11] accumulate in
      stunted cilia, suggesting that abnormal or lack of cilia or defects in IFT may
      result in diseases such as polycystic kidney disease (PKD).

PMID- 11301259
TI  - Europe opens the door to GM crops.

PMID- 11301260
TI  - GM crops under new US scrutiny.

PMID- 11301261
TI  - Genome jousting enlivens a sporting lull.

PMID- 11301262
TI  - Meagre numbers raise genome questions.

PMID- 11301263
TI  - Structural and functional features of the intracellular amino terminus of
      DEG/ENaC ion channels.

PMID- 11301264
TI  - Growth control: invertebrate insulin surprises!
AB  - Recent work on Drosophila has provided new insights into how insulin signalling -
      conserved in mammals, flies and worms - regulates growth and cell division during
      development. Invertebrates have been found to possess more insulin-like ligands
      than predicted, some of which behave as receptor antagonists.

PMID- 11301265
TI  - Cellulose: how many cellulose synthases to make a plant?
AB  - Many questions remain about the biosynthesis of cellulose, the major plant cell
      wall component, not least of which is why plants have so many genes for the
      cellulose synthase catalytic subunit. Perhaps multiple isoforms of cellulose
      synthase are needed in the same cell for the formation of functional dimeric
      complexes.

PMID- 11301266
TI  - Notch pathway: making sense of suppressor of hairless.
AB  - Suppressor of Hairless (Su(H)) is a DNA-binding protein component of the Notch
      signalling pathway, thought to be required, with a fragment of the Notch
      receptor, for target gene activation. Recent studies show that this is only one
      side of the story: target gene enhancers may be regulated by Su(H) in a variety
      of different ways.

PMID- 11301267
TI  - Bacterial cell cycle: seeing the big picture with microarrays.
AB  - Global assays of gene expression and protein stability during the Caulobacter
      crescentus cell cycle reveal that a surprisingly large fraction of the genome and
      proteome is affected as cells grow and divide. These studies are an important
      step toward understanding how the cell cycle is controlled in prokaryotes.

PMID- 11301268
TI  - Potassium channels: the importance of transport signals.
AB  - The number, type and distribution of ion channels on a neuron's surface determine
      its electrical response to stimulation. One way that a cell determines how many
      molecules of each channel type are sent to the surface has been eludicated in a
      recent study of intrinsic protein transport signals within potassium channels.

PMID- 11301269
TI  - DNA repair: spot(light)s on chromatin.
AB  - Chromatin modifications regulate many nuclear processes. Recent studies on the
      phosphorylation of a histone 2A variant have revealed that this chromatin
      modification is a general and evolutionarily conserved cellular response to DNA
      double-strand breaks.

PMID- 11301270
TI  - Asymmetric cell division: plane but not simple.
AB  - The polarity of sensory bristles on the thorax of Drosophila is linked to the
      orientation of the asymmetric cell divisions that partition cell fate
      determinants in this lineage. The orientation of these divisions is under the
      control of the Frizzled pathway that generates planar polarity in a number of
      cell types.

PMID- 11301271
TI  - Muscle development: reversal of the differentiated state.
AB  - Cell fate selection and cell cycle exit are fundamental features of
      differentiation during animal development. Accumulating data suggest that these
      processes are more readily reversible than previously supposed and are beginning
      to point at the underlying molecular mechanisms.

PMID- 11301273
TI  - BBB-Genomics: creating new openings for brain-drug targeting.

PMID- 11301272
TI  - Functional anatomy: from molecule to memory.
AB  - The Drosophila memory gene amnesiac is expressed in neurons that project to
      mushroom body axons. Blockade of synaptic transmission in the amnesiac-expressing
      cells disrupts memory, but not learning, suggesting presynaptic and postsynaptic
      sites for memory formation.

PMID- 11301274
TI  - Holy Grail of drug delivery caught using novel fishnet technology.

PMID- 11301275
TI  - Sixth sense could avoid the blood-brain barrier.

PMID- 11301276
TI  - Drugs with a magnetic attraction to tumours.

PMID- 11301280
TI  - Too many targets, not enough target validation.

PMID- 11301279
TI  - Crystal gazing - seeking that elusive polymorph.

PMID- 11301281
TI  - Drug discoverers -you need us!

PMID- 11301282
TI  - Education: the chemistry between academia and industry - Reply.

PMID- 11301283
TI  - Look out: here come the proteins.

PMID- 11301284
TI  - Biocomputing: impact of the genomic revolution.

PMID- 11301285
TI  - Microwave-assisted high-speed chemistry: a new technique in drug discovery.
AB  - In both lead identification and lead optimization processes there is an acute
      need for new organic small molecules. Traditional methods of organic synthesis
      are orders of magnitude too slow to satisfy the demand for these compounds. The
      fields of combinatorial and automated medicinal chemistry have been developed to
      meet the increasing requirement of new compounds for drug discovery; within these
      fields, speed is of the essence. The efficiency of microwave flash-heating
      chemistry in dramatically reducing reaction times (reduced from days and hours to
      minutes and seconds) has recently been proven in several different fields of
      organic chemistry. We believe that the time saved by using focused microwaves is
      potentially important in traditional organic synthesis but could be of even
      greater importance in high-speed combinatorial and medicinal chemistry.

PMID- 11301286
TI  - TACE and other ADAM proteases as targets for drug discovery.
AB  - Tumor necrosis factor (TNF)-converting enzyme (TACE) and other ADAM proteases
      (those that contain a disintegrin and a metalloprotease domain) have emerged as
      potential therapeutic targets in the areas of arthritis, cancer, diabetes and HIV
      cachexia. TACE is the first ADAM protease to process the known physiological
      substrate and inflammatory cytokine, membrane-bound precursor-TNF-alpha, to its
      mature soluble form. Subsequently, TACE was shown to be required for several
      different processing events such as tumor growth factor-alpha (TGF-alpha)
      precursor and amyloid precursor protein (APP) cleavage. With the recent
      discoveries of the proteolytic specificities of other ADAM family members, the
      information surrounding these metalloproteases is expanding at an exponential
      rate. This review focuses on TACE and other family members with known proteolytic
      function as well as the inhibitors of this class of enzyme.

PMID- 11301287
TI  - Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and
      biomedical applications.
AB  - Poly(amidoamine) (PAMAM) dendrimers are the first complete dendrimer family to be
      synthesized, characterized and commercialized. Based on this extensive activity,
      they are recognized as a unique new class of synthetic nanostructures. Dendrimers
      allow the precise control of size, shape and placement of functional groups that
      is desirable for many life science applications. From this perspective, this
      review focuses on crucial properties of biomimetic dendrimers that will broaden
      the potential for their use as macromolecular vectors in novel drug delivery and
      biomedical applications.

PMID- 11301288
TI  - NF-kappaB and AP-1 gene expression inhibitors.

PMID- 11301289
TI  - HIV-1 protease inhibitors.

PMID- 11301290
TI  - Influence of different essential and non-essential metals on MTLP levels in the
      Copepod Tigriopus brevicornis.
AB  - Because of their wide geographic distribution, position in the trophic chain,
      rapid turnover, huge biomass and role in ocean biogeochemical cycles, copepods
      are regarded as important marine test species. Tigriopus brevicornis Muller, 1776
      is a shallow water benthic marine species (Crustacea, Copepoda Harpacticoida).
      The toxicity of essential and non-essential metals (Ag, Cd, Cu, Hg, Ni and Zn) to
      Tigriopus brevicornis was determined by 96-h LC(50) testing. Comparative
      crustacean 96-h LC(50) data in the literature show that Tigriopus brevicornis is
      a sensitive species suggesting that copepods are good indicators of minimal
      lethal concentrations of metals. Groups of 1000 to 1500 adult copepods were
      exposed for 1 to 14 days to metals at concentrations in water, 3 for each metal,
      considered realistic in comparison with those encountered in polluted
      environments and far below lethal concentrations, in order to avoid protein
      metabolism disturbance. The response of Tigriopus brevicornis in terms of MT
      induction has been examined in specimens exposed to metals. The induction of
      these proteins and their implication in detoxificatory mechanisms and trophic
      transfer are discussed.

PMID- 11301291
TI  - Effects of endothelin-1 and nitric oxide on proliferation of cultured guinea pig
      bronchial smooth muscle cells.
AB  - The proliferative effects of endothelin-1 (ET-1), both alone and in combination
      with epidermal growth factor (EGF), and the effect of nitric oxide (NO) on the
      cell proliferation were investigated in cultured guinea pig bronchial smooth
      muscle cells. ET-1 (10-100 nM) alone augmented cell proliferation, and was
      additive to the effect of EGF (0.48 nM) in a concentration-dependent manner. An
      ET(A) antagonist, BQ-123 (10 microM), reduced the cell-proliferative effect of ET
      1, whereas an ET(B) antagonist, BQ-788 (10 microM), did not influence the effect.
      A NO donor, SIN-1 (10 nM-1 microM), reduced the cell-proliferative effect of ET-1
      in a concentration-dependent manner. The effect of SIN-1 (1 microM) was partly,
      but significantly, reversed by a soluble guanylyl cyclase inhibitor, ODQ (1
      microM). These results suggest that ET-1 acts not only as a co-mitogen with EGF
      but also as a mitogen alone, and that its action is mediated through activation
      of ET(A) receptors. Therefore, ET-1 may contribute to airway remodeling, a
      pathophysiological hallmark of asthma. In addition, NO, which is produced mainly
      in the airway epithelium and is partly mediated through cGMP-dependent pathway,
      may reduce the phenomenon.

PMID- 11301292
TI  - Oxidative stress, microsomal and peroxisomal fatty acid oxidation in the liver of
      rats treated with acetone.
AB  - Parameters of oxidative stress, microsomal cytochrome P450 activity and
      peroxisomal fatty acid oxidation were studied in liver of rats following acetone
      (1% v/v) consumption for 7 days. Acetone treatment increased the activity of
      catalase and decreased the activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GTPx), but did not significantly modify the liver content
      of malondialdehyde (MDA) and reduced glutathione. Also, acetone increased the
      total content of cytochrome P450, the microsomal lauric acid hydroxylation,
      aminopyrine N-demethylation and the peroxisomal beta-oxidation of palmitoyl CoA.
      These effects were similar to those found previously in starved and ethanol
      treated rats, supporting the hypothesis that ketone bodies would be the common
      inducer of microsomal and peroxisomal fatty acid oxidation in these metabolic
      states.

PMID- 11301293
TI  - Ouabain-sensitive and insensitive acetylcholine receptors on the membrane of the
      same neuron in Helix pomatia.
AB  - Using internally dialyzed neurons of Helix pomatia as a model, the effect of
      structural analogs of acetylcholine (ACh) were investigated for their
      cholinomimetic properties on A- and B-types of ACh-responses. Specifically we
      analyzed choline esters of N-para- and ortho-alkoxybenzoyl-beta-alanines, (CH(3)O
      , C(2)H(5)O-, C(3)H(7)O-, iso-C(3)H(7)O-, C(4)H(9)O-, iso-C(4)H(9)O-, C(5)H(11)O
      , iso-C(5)H(11)O-), (in all, 16 combinations). The compounds evoked differing
      sensitivities of response to factors de-activating the Na-K-pump (ouabain and K
      free solution). Most compounds resembled ACh: ionic currents caused by these
      compounds were inhibited by Na-K pump blockers in the case of A-type responses -
      B-type responses were insensitive to these factors. Ionic currents induced by
      choline esters of p-, o-propoxy- and iso-propoxybenzoyl-beta-alanines were
      insensitive to ouabain and K-free solution in the case of A- and B-type
      responses. Ionic currents induced by the choline ester of p-butoxybenzoyl-beta
      alanine were inhibited by ouabain and K-free solution on both types of neuron.
      The results allow us to classify choline esters of p-, o-propoxy- and iso
      propoxybenzoyl-beta-alanines as N-cholinomimetics, while the choline ester of p
      butoxybenzoyl-beta-alanine can be considered as M-cholinomimetic. We conclude
      that both M- and N-type ACh receptors exist on the membrane of the same neurons.

PMID- 11301294
TI  - Chemotactic selection with insulin, di-iodotyrosine and histamine alters the
      phagocytotic responsiveness of Tetrahymena.
AB  - Chemotactic selection is a method by which populations of cells exposed to
      ligands can be isolated and subsequently cultivated. We used Tetrahymena
      pyriformis GL cultures selected by chemotactic selection to insulin (10 nM),
      histamine (0.1 nM) and di-iodotyrosine (T2, 10 nM) to study the phagocytotic
      capacity under the induction of selector hormones. Our results show a long
      lasting link between chemotactically selected cultures and phagocytotic activity.
      Cells selected to histamine produced the highest phagocytotic activity upon a
      second exposure to the selector hormone. T2 selection was also strongly
      effective, however, the phagocytosis stimulation was not specific to the hormone
      given later. Insulin selected sub-populations had different phagocytotic
      responses to the control substance itself, whereas histamine selected sub
      populations seem to be heterogeneous in the phagocytotic response to histamine.
      For insulin, the increased endocytotic or metabolic activity was demonstrated by
      the lack of non-phagocytotic cells. These experiments call attention to the
      evolutionary role of selection in the later developing receptor-hormone
      relationship.

PMID- 11301295
TI  - Halenaquinol, a natural cardioactive pentacyclic hydroquinone, interacts with
      sulfhydryls on rat brain Na(+),K(+)-ATPase.
AB  - Halenaquinol inhibited the partial reactions of ATP hydrolysis by rat brain
      cortex Na(+),K(+)-ATPase, such as [3H]ATP binding to the enzyme, Na(+)-dependent
      front-door phosphorylation from [gamma-(33)P]ATP, and also Na(+)- and K(+)
      dependent E(1)<-->E(2) conformational transitions of the enzyme. Halenaquinol
      abolished the positive cooperativity between the Na(+)- and K(+)-binding sites on
      the enzyme. ATP and sulfhydryl-containing reagents (cysteine and dithiothreitol)
      protected the Na(+),K(+)-ATPase against inhibition. Halenaquinol can react with
      additional vital groups in the enzyme after blockage of certain sulfhydryl groups
      with 5,5'-dithio-bis-nitrobenzoic acid. Halenaquinol inhibited [3H]ouabain
      binding to Na(+),K(+)-ATPase under phosphorylating and non-phosphorylating
      conditions. Binding of fluorescein 5'-isothiocyanate to Na(+),K(+)-ATPase and
      intensity of fluorescence of enzyme tryptophanyl residues were decreased by
      halenaquinol. We suggest that interaction of halenaquinol with the essential
      sulfhydryls in/or near the ATP-binding site of Na(+),K(+)-ATPase resulted in a
      change of protein conformation and subsequent alteration of overall and partial
      enzymatic reactions.

PMID- 11301297
TI  - Time to defend what we have won.

PMID- 11301296
TI  - Possible effects of counterions on biological activities of anionic surfactants.
AB  - The aggressiveness in terms of apogenic and necrotic activities of lysine-derived
      anionic surfactants towards a mammalian cell line (U937) were studied. We used
      N(alpha)N(epsilon)-dioctanoyl lysine as the model surfactant with lysine, tris,
      Na(+) or Li(+) as counterions. The aggressiveness of the different surfactants
      was assessed as the concentrations leading to apoptosis or necrosis after the
      cells were incubated in the presence of surfactants and then cultivated in their
      absence. Used in the same conditions, acetates associated with the same cations,
      had no effects on the cells. Our results show that the aggressiveness of the
      surfactants depended on the nature of the counterions: it was high when
      surfactants were associated with small counterions, and low with large
      counterions.

PMID- 11301298
TI  - A relational schema for both array-based and SAGE gene expression experiments.
AB  - MOTIVATION AND RESULTS: A relational schema is described for capturing highly
      parallel gene expression experiments using different technologies. This schema
      grew out of efforts to build a database for collaborators working on different
      biological systems and using different types of platforms in their gene
      expression experiments as well as different types of image quantification
      software. The tables are conceptually organized into three categories of
      information: Platform, Experiment (which includes image scanning and
      quantification), and Data. The strengths of the schema are: (i) integrating
      information on array elements using a gene index; (ii) describing samples using
      ontologies; (iii) reducing an experiment to a single RNA source for precise
      descriptions yet not losing the relationships between experiments done at the
      same time or for the same project; and (iv) maintaining both raw and processed
      (e.g. cleansed and normalized) data and recording how the data is processed. The
      result is a novel schema, which can hold both array and non-array data, is
      extensible for detailed experimental descriptions that are precise and
      consistent, and allows for meaningful comparisons of genes between experiments.

PMID- 11301299
TI  - Validating clustering for gene expression data.
AB  - MOTIVATION: Many clustering algorithms have been proposed for the analysis of
      gene expression data, but little guidance is available to help choose among them.
      We provide a systematic framework for assessing the results of clustering
      algorithms. Clustering algorithms attempt to partition the genes into groups
      exhibiting similar patterns of variation in expression level. Our methodology is
      to apply a clustering algorithm to the data from all but one experimental
      condition. The remaining condition is used to assess the predictive power of the
      resulting clusters-meaningful clusters should exhibit less variation in the
      remaining condition than clusters formed by chance. RESULTS: We successfully
      applied our methodology to compare six clustering algorithms on four gene
      expression data sets. We found our quantitative measures of cluster quality to be
      positively correlated with external standards of cluster quality.

PMID- 11301300
TI  - Use of keyword hierarchies to interpret gene expression patterns.
AB  - MOTIVATION: High-density microarray technology permits the quantitative and
      simultaneous monitoring of thousands of genes. The interpretation challenge is to
      extract relevant information from this large amount of data. A growing variety of
      statistical analysis approaches are available to identify clusters of genes that
      share common expression characteristics, but provide no information regarding the
      biological similarities of genes within clusters. The published literature
      provides a potential source of information to assist in interpretation of
      clustering results. RESULTS: We describe a data mining method that uses indexing
      terms ('keywords') from the published literature linked to specific genes to
      present a view of the conceptual similarity of genes within a cluster or group of
      interest. The method takes advantage of the hierarchical nature of Medical
      Subject Headings used to index citations in the MEDLINE database, and the
      registry numbers applied to enzymes.

PMID- 11301301
TI  - A new approach to sequence comparison: normalized sequence alignment.
AB  - The Smith-Waterman algorithm for local sequence alignment is one of the most
      important techniques in computational molecular biology. This ingenious dynamic
      programming approach was designed to reveal the highly conserved fragments by
      discarding poorly conserved initial and terminal segments. However, the existing
      notion of local similarity has a serious flaw: it does not discard poorly
      conserved intermediate segments. The Smith-Waterman algorithm finds the local
      alignment with maximal score but it is unable to find local alignment with
      maximum degree of similarity (e.g. maximal percent of matches). Moreover, there
      is still no efficient algorithm that answers the following natural question: do
      two sequences share a (sufficiently long) fragment with more than 70% of
      similarity? As a result, the local alignment sometimes produces a mosaic of well
      conserved fragments artificially connected by poorly-conserved or even unrelated
      fragments. This may lead to problems in comparison of long genomic sequences and
      comparative gene prediction as recently pointed out by Zhang et al.
      (Bioinformatics, 15, 1012-1019, 1999). In this paper we propose a new sequence
      comparison algorithm (normalized local alignment ) that reports the regions with
      maximum degree of similarity. The algorithm is based on fractional programming
      and its running time is O(n2log n). In practice, normalized local alignment is
      only 3-5 times slower than the standard Smith-Waterman algorithm.

PMID- 11301302
TI  - Limits of homology detection by pairwise sequence comparison.
AB  - MOTIVATION: Noise in database searches resulting from random sequence
      similarities increases as the databases expand rapidly. The noise problems are
      not a technical shortcoming of the database search programs, but a logical
      consequence of the idea of homology searches. The effect can be observed in
      simulation experiments. RESULTS: We have investigated noise levels in pairwise
      alignment based database searches. The noise levels of 38 releases of the
      SwissProt database, display perfect logarithmic growth with the total length of
      the databases. Clustering of real biological sequences reduces noise levels, but
      the effect is marginal.

PMID- 11301303
TI  - NIFAS: visual analysis of domain evolution in proteins.
AB  - MOTIVATION: Multi-domain proteins have evolved by insertions or deletions of
      distinct protein domains. Tracing the history of a certain domain combination can
      be important for functional annotation of multi-domain proteins, and for
      understanding the function of individual domains. In order to analyze the
      evolutionary history of the domains in modular proteins it is desirable to
      inspect a phylogenetic tree based on sequence divergence with the modular
      architecture of the sequences superimposed on the tree. RESULT: A Java applet,
      NIFAS, that integrates graphical domain schematics for each sequence in an
      evolutionary tree was developed. NIFAS retrieves domain information from the Pfam
      database and uses CLUSTAL W to calculate a tree for a given Pfam domain. The tree
      can be displayed with symbolic bootstrap values, and to allow the user to focus
      on a part of the tree, the layout can be altered by swapping nodes, changing the
      outgroup, and showing/collapsing subtrees. NIFAS is integrated with the Pfam
      database and is accessible over the internet (http://www.cgr.ki.se/Pfam). As an
      example, we use NIFAS to analyze the evolution of domains in Protein Kinases C.

PMID- 11301304
TI  - Multi-class protein fold recognition using support vector machines and neural
      networks.
AB  - MOTIVATION: Protein fold recognition is an important approach to structure
      discovery without relying on sequence similarity. We study this approach with new
      multi-class classification methods and examined many issues important for a
      practical recognition system. RESULTS: Most current discriminative methods for
      protein fold prediction use the one-against-others method, which has the well
      known 'False Positives' problem. We investigated two new methods: the unique one
      against-others and the all-against-all methods. Both improve prediction accuracy
      by 14-110% on a dataset containing 27 SCOP folds. We used the Support Vector
      Machine (SVM) and the Neural Network (NN) learning methods as base classifiers.
      SVMs converges fast and leads to high accuracy. When scores of multiple parameter
      datasets are combined, majority voting reduces noise and increases recognition
      accuracy. We examined many issues involved with large number of classes,
      including dependencies of prediction accuracy on the number of folds and on the
      number of representatives in a fold. Overall, recognition systems achieve 56%
      fold prediction accuracy on a protein test dataset, where most of the proteins
      have below 25% sequence identity with the proteins used in training.

PMID- 11301305
TI  - Mining literature for protein-protein interactions.
AB  - MOTIVATION: A central problem in bioinformatics is how to capture information
      from the vast current scientific literature in a form suitable for analysis by
      computer. We address the special case of information on protein-protein
      interactions, and show that the frequencies of words in Medline abstracts can be
      used to determine whether or not a given paper discusses protein-protein
      interactions. For those papers determined to discuss this topic, the relevant
      information can be captured for the Database of Interacting PROTEINS:
      Furthermore, suitable gene annotations can also be captured. RESULTS: Our
      Bayesian approach scores Medline abstracts for probability of discussing the
      topic of interest according to the frequencies of discriminating words found in
      the abstract. More than 80 discriminating words (e.g. complex, interaction, two
      hybrid) were determined from a training set of 260 Medline abstracts
      corresponding to previously validated entries in the Database of Interacting
      Proteins. Using these words and a log likelihood scoring function, approximately
      2000 Medline abstracts were identified as describing interactions between yeast
      proteins. This approach now forms the basis for the rapid expansion of the
      Database of Interacting Proteins.

PMID- 11301306
TI  - Strategies for the development of a peptide computer.
AB  - MOTIVATION: We devise a computational model using protein-protein interactions.
      RESULTS: Peptide-antibody interactions can be used to perform a large number of
      small logical operations in parallel. We show for example how a sequence of
      operations can be used to compare the number of occurrences of an element in two
      sets and how to estimate the number of occurrences of an element in a set.
      Similar to DNA-computing, these techniques could in principle be extended to
      solve instances of NP-complete problems. We give as an example a procedure to
      solve examples of the satisfiability problem.

PMID- 11301307
TI  - J-Express: exploring gene expression data using Java.
AB  - J-Express is a Java application that allows the user to analyze gene expression
      (microarray) data in a flexible way giving access to multidimensional scaling,
      clustering, and visualization methods in an integrated manner. Specifically, J
      Express includes implementations of hierarchical clustering, k-means, principal
      component analysis, and self-organizing maps. At present, it does not include
      methods for comparing two or more experiments for differentially expressed genes.
      The application is completely portable and requires only that a Java runtime
      environment 1.2 is installed on the system. Its efficiency allows interactive
      clustering of thousands of expression profiles on standard personal computers.

PMID- 11301308
TI  - DeFries-Fulker multiple regression analysis of sibship QTL data: a SAS macro.
AB  - A SAS macro package for performing multipoint QTL mapping using the DeFries
      Fulker multiple regression method is presented.

PMID- 11301309
TI  - Mocca: semi-automatic method for domain hunting.
AB  - MOTIVATION: Multiple OCCurrences Analysis (Mocca) is a new method for repeat
      extraction. It is based on the T-Coffee package (Notredame et al., JMB, 302, 205
      217, 2000). Given a sequence or a set of sequences, and a library of local
      alignments, Mocca extracts every segment of sequence homologous to a pre
      specified master. The implementation is meant for domain hunting and makes it
      fast and easy to test for new boundaries or extend known repeats in an
      interactive manner. Mocca is designed to deal with highly divergent protein
      repeats (less than 30% amino acid identity) of more than 30 amino acids.

PMID- 11301310
TI  - PALI: a database of alignments and phylogeny of homologous protein structures.
AB  - PALI is a database of structure-based sequence alignments and phylogenetic
      relationships derived on the basis of three-dimensional structures of homologous
      proteins. This database enables grouping of pairs of homologous protein
      structures on the basis of their sequence identity calculated from the structure
      based alignment and PALI also enables association of a new sequence to a family
      and automatic generation of a dendrogram combining the query sequence and
      homologous protein structures.

PMID- 11301311
TI  - STRAP: editor for STRuctural Alignments of Proteins.
AB  - STRAP is a comfortable and extensible tool for the generation and refinement of
      multiple alignments of protein sequences. Various sequence ordered input file
      formats are supported. These are the SwissProt-,GenBank-, EMBL-, DSSP- PDB-, MSF
      , and plain ASCII text format. The special feature of STRAP is the simple
      visualization of spatial distances C(alpha)-atoms within the alignment. Thus
      structural information can easily be incorporated into the sequence alignment and
      can guide the alignment process in cases of low sequence similarities. Further
      STRAP is able to manage huge alignments comprising a lot of sequences. The
      protein viewers and modeling programs INSIGHT, RASMOL and WEBMOL are embedded
      into STRAP. STRAP is written in JAVA: The well-documented source code can be
      adapted easily to special requirements. STRAP may become the basis for complex
      alignment tools in the future.

PMID- 11301312
TI  - ProDDO: a database of disordered proteins from the Protein Data Bank (PDB).
AB  - ProDDO represents a 'pre-screened' database that denotes disorder (or possible
      disorder) in proteins from the PDB.

PMID- 11301313
TI  - MutaProt: a web interface for structural analysis of point mutations.
AB  - A web-based tool, termed 'MutaProt', is described which analyses pairs of PDB
      files whose members differ in one, or two, amino acids. MutaProt examines the
      micro environment surrounding the exchanged residue(s) and can be searched by
      specifying a PDB ID, keywords, or any pair of amino acids. Detailed information
      about accessibility of the exchanged residue(s) and its atomic contacts are
      provided based on CSU software (Sobolev et al., Bioinformatics, 15, 327-332,
      1999). An interactive 3D presentation of the superimposed regions around the
      mutation(s) is included. MutaProt is updated weekly.

PMID- 11301314
TI  - ATV: display and manipulation of annotated phylogenetic trees.
AB  - A Tree Viewer (ATV) is a Java tool for the display and manipulation of annotated
      phylogenetic trees. It can be utilized both as a standalone application and as an
      applet in a web browser.

PMID- 11301315
TI  - PhyloBLAST: facilitating phylogenetic analysis of BLAST results.
AB  - PhyloBLAST is an internet-accessed application based on CGI/Perl programming that
      compares a users protein sequence to a SwissProt/TREMBL database using BLAST2 and
      then allows phylogenetic analyses to be performed on selected sequences from the
      BLAST output. Flexible features such as ability to input your own multiple
      sequence alignment and use PHYLIP program options provide additional web-based
      phylogenetic analysis functionality beyond the analysis of a BLAST result.

PMID- 11301316
TI  - A novel protein interacts with the Werner's syndrome gene product physically and
      functionally.
AB  - Werner's syndrome (WS) is a rare autosomal recessive disorder characterized by
      premature aging. The gene responsible for WS encodes a protein homologous to
      Escherichia coli RecQ. Here we describe a novel Werner helicase interacting
      protein (WHIP), which interacts with the N-terminal portion of Werner protein
      (WRN), containing the exonuclease domain. WHIP, which shows homology to
      replication factor C family proteins, is conserved from E. coli to human.
      Ectopically expressed WHIP and WRN co-localized in granular structures in the
      nucleus. The functional relationship between WHIP and WRN was indicated by
      genetic analysis of yeast cells. Disruptants of the SGS1 gene of Saccharomyces
      cerevisiae, which is the WRN homologue in yeast, show an accelerated aging
      phenotype and high sensitivity to methyl methanesulfonate as compared with wild
      type cells. Disruption of the yeast WHIP (yWHIP) gene in wild-type cells and sgs1
      disruptants resulted in slightly accelerated aging and enhancement of the
      premature aging phenotype of sgs1 disruptants, respectively. In contrast,
      disruption of the yWHIP gene partially alleviated the sensitivity to methyl
      methanesulfonate of sgs1 disruptants.

PMID- 11301317
TI  - Identification of a dominant negative homeodomain mutation in Rieger syndrome.
AB  - Mutations in the PITX2 bicoid-like homeobox gene cause Rieger syndrome. Rieger
      syndrome is an autosomal-dominant human disorder characterized by glaucoma as
      well as dental hypoplasia, mild craniofacial dysmorphism, and umbilical stump
      abnormalities. PITX2 has also been implicated in the development of multiple
      organs and left-right asymmetry in the body plan. The PITX2 homeodomain has a
      lysine at position 50, which has been shown to impart the bicoid-type (TAATCC)
      DNA binding specificity to other homeodomain proteins. A mutation (K88E), found
      in a Rieger syndrome patient, changes this lysine to glutamic acid. We were
      intrigued by the relatively pronounced phenotypic consequences of this K88E
      mutation. In the initial analyses, the mutant protein appeared to simply be
      inactive, with essentially no DNA binding and transactivation activities and,
      unlike the wild type protein, with an inability to synergize with another
      transcription factor, Pit-1. However, when the K88E DNA was cotransfected with
      wild type PITX2, analogous to the patient genotype, the K88E mutant suppressed
      the synergism of wild type PITX2 with Pit-1. In contrast, a different PITX2
      homeodomain mutant, T68P, which is also defective in DNA binding,
      transactivation, and Pit-1 synergism activities, did not suppress the wild type
      synergism with Pit-1. These results describe the first dominant negative missense
      mutation in a homeodomain and support a model that may partially explain the
      phenotypic variation within Rieger syndrome.

PMID- 11301318
TI  - EWS/FLI alters 5'-splice site selection.
AB  - The chimeric gene EWS/FLI is present in at least 85% of Ewing's sarcomas as a
      result of chromosomal translocations. The resulting fusion protein contains the N
      terminus of the RNA-binding protein EWS and the ETS DNA-binding domain of the
      transcription factor FLI-1. Although EWS/FLI binds DNA and activates
      transcription, both EWS and EWS/FLI also interact with SF1 and U1C, essential
      components of the splicing machinery. Therefore, we tested the ability of EWS and
      EWS/FLI to alter 5'-splice site selection using an E1A gene in vivo splicing
      assay. We found that EWS/FLI, but not EWS, interfered with heterogeneous nuclear
      ribonucleoprotein A1-dependent splice site selection of E1A. Mutational analysis
      of EWS/FLI revealed that the ability to affect pre-mRNA splicing coincided with
      transforming activity. Therefore, EWS/FLI has the ability to influence splicing
      as well as transcription.

PMID- 11301319
TI  - The effect of substrate, dihydrobiopterin, and dopamine on the EPR spectroscopic
      properties and the midpoint potential of the catalytic iron in recombinant human
      phenylalanine hydroxylase.
AB  - Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin (BH(4)) and non-heme
      iron-dependent enzyme that hydroxylates L-Phe to L-Tyr. The paramagnetic ferric
      iron at the active site of recombinant human PAH (hPAH) and its midpoint
      potential at pH 7.25 (E(m)(Fe(III)/Fe(II))) were studied by EPR spectroscopy.
      Similar EPR spectra were obtained for the tetrameric wild-type (wt-hPAH) and the
      dimeric truncated hPAH(Gly(103)-Gln(428)) corresponding to the "catalytic
      domain." A rhombic high spin Fe(III) signal with a g value of 4.3 dominates the
      EPR spectra at 3.6 K of both enzyme forms. An E(m) = +207 +/- 10 mV was measured
      for the iron in wt-hPAH, which seems to be adequate for a thermodynamically
      feasible electron transfer from BH(4) (E(m) (quinonoid-BH(2)/BH(4)) = +174 mV).
      The broad EPR features from g = 9.7-4.3 in the spectra of the ligand-free enzyme
      decreased in intensity upon the addition of L-Phe, whereas more axial type
      signals were observed upon binding of 7,8-dihydrobiopterin (BH(2)), the stable
      oxidized form of BH(4), and of dopamine. All three ligands induced a decrease in
      the E(m) value of the iron to +123 +/- 4 mV (L-Phe), +110 +/- 20 mV (BH(2)), and 
      8 +/- 9 mV (dopamine). On the basis of these data we have calculated that the
      binding affinities of L-Phe, BH(2), and dopamine decrease by 28-, 47-, and 5040
      fold, respectively, for the reduced ferrous form of the enzyme, with respect to
      the ferric form. Interestingly, an E(m) value comparable with that of the ligand
      free, resting form of wt-hPAH, i.e. +191 +/- 11 mV, was measured upon the
      simultaneous binding of both L-Phe and BH(2), representing an inactive model for
      the iron environment under turnover conditions. Our findings provide new
      information on the redox properties of the active site iron relevant for the
      understanding of the reductive activation of the enzyme and the catalytic
      mechanism.

PMID- 11301320
TI  - Growth factors signal to steroid receptors through mitogen-activated protein
      kinase regulation of p160 coactivator activity.
AB  - Promoter-bound steroid receptors activate gene expression by recruiting members
      of the p160 family of coactivators. Many steroid receptors, most notably the
      progesterone and estrogen receptors, are regulated both by cognate hormone and
      independently by growth factors. Here we show that epidermal growth factor
      regulates the activities of the p160 GRIP1 through the extracellular signal
      regulated kinase (ERK) family of mitogen-activated protein kinases. ERKs
      phosphorylate GRIP1 at a specific site, Ser-736, the integrity of which is
      required for full growth factor induction of GRIP1 transcriptional activation and
      coactivator function. We propose that growth factors signal to nuclear receptors
      in part by targeting the p160 coactivators.

PMID- 11301321
TI  - Intracellular chelation of iron by bipyridyl inhibits DNA virus replication:
      ribonucleotide reductase maturation as a probe of intracellular iron pools.
AB  - The efficient replication of large DNA viruses requires dNTPs supplied by a viral
      ribonucleotide reductase. Viral ribonucleotide reductase is an early gene product
      of both vaccinia and herpes simplex virus. For productive infection, the
      apoprotein must scavenge iron from the endogenous, labile iron pool(s). The
      membrane-permeant, intracellular Fe(2+) chelator, 2,2'-bipyridine (bipyridyl,
      BIP), is known to sequester iron from this pool. We show here that BIP strongly
      inhibits the replication of both vaccinia and herpes simplex virus, type 1. In a
      standard plaque assay, 50 microm BIP caused a 50% reduction in plaque-forming
      units with either virus. Strong inhibition was observed only when BIP was added
      within 3 h post-infection. This time dependence was observed also in regards to
      inhibition of viral late protein and DNA synthesis by BIP. BIP did not inhibit
      the activity of vaccinia ribonucleotide reductase (RR), its synthesis, nor its
      stability indicating that BIP blocked the activation of the apoprotein. In
      parallel with its inhibition of vaccinia RR activation, BIP treatment increased
      the RNA binding activity of the endogenous iron-response protein, IRP1, by 1.9
      fold. The data indicate that the diiron prosthetic group in vaccinia RR is
      assembled from iron taken from the BIP-accessible, labile iron pool that is
      sampled also by ferritin and the iron-regulated protein found in the cytosol of
      mammalian cells.

PMID- 11301322
TI  - PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and
      promyelocytic leukemia (PML)-RA receptor alpha in acute promyelocytic leukemia
      cells.
AB  - The t(15;17) translocation, found in 95% of acute promyelocytic leukemia, encodes
      a promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARalpha) fusion
      protein. Complete remission of acute promyelocytic leukemia can be obtained by
      treating patients with all-trans retinoic acid, and PML-RARalpha plays a major
      role in mediating retinoic acid effects in leukemia cells. A main model proposed
      for acute promyelocytic leukemia is that PML-RARalpha exerts its oncogenic
      effects by repressing the expression of retinoic acid-inducible genes critical to
      myeloid differentiation. By applying subtraction cloning to acute promyelocytic
      leukemia cells, we identified a retinoic acid-induced gene, PRAM-1 (PML-RARalpha
      target gene encoding an Adaptor Molecule-1), which encodes a novel adaptor
      protein sharing structural homologies with the SLAP-130/fyb adaptor. PRAM-1 is
      expressed and regulated during normal human myelopoiesis. In U937 myeloid
      precursor cells, PRAM-1 expression is inhibited by expression of PML-RARalpha in
      the absence of ligand and de novo superinduced by retinoic acid. PRAM-1
      associates with other adaptors, SLP-76 and SKAP-55HOM, in myeloid cell lines and
      with protein tyrosine kinase lyn. By providing the first evidence that PML
      RARalpha dysregulates expression of an adaptor protein, our data open new
      insights into signaling events that are disrupted during transformation by PML
      RARalpha and induced by retinoic acid during de novo differentiation of acute
      promyelocytic leukemia cells.

PMID- 11301323
TI  - The WD motif-containing protein receptor for activated protein kinase C (RACK1)
      is required for recruitment and activation of signal transducer and activator of
      transcription 1 through the type I interferon receptor.
AB  - An obligatory step in the activation of Signal Transducers and Activators of
      Transcription (STATs) by cytokines is their docking to specific receptors via
      phosphotyrosines. However, this model does not address whether STATs pre
      associate with their corresponding receptor or exist free in the cytoplasm before
      receptor activation. In this report, we demonstrate that pre-association of STAT1
      with the receptor is required for type I interferon (IFN) signaling.
      Interestingly, the interaction between the human type I IFN receptor and STAT1 is
      not direct but mediated by the adapter protein receptor for activated protein
      kinase C (RACK1). Disruption of the IFNalpha receptor-RACK1 interaction abolishes
      not only IFNalpha-induced tyrosine phosphorylation of STAT1 but also activation
      of STAT2, indicating that RACK1 plays a central role in early signaling through
      the Jak-STAT pathway. These findings demonstrate the involvement of RACK1 in
      STAT1 activation and raise the possibility that other STATs may pre-associate
      with cytokine receptors through similar adapter-STAT-mediated interactions.

PMID- 11301324
TI  - Calcium transients in 1B5 myotubes lacking ryanodine receptors are related to
      inositol trisphosphate receptors.
AB  - Potassium depolarization of skeletal myotubes evokes slow calcium waves that are
      unrelated to contraction and involve the cell nucleus (Jaimovich, E., Reyes, R.,
      Liberona, J. L., and Powell, J. A. (2000) Am. J. Physiol. 278, C998-C1010).
      Studies were done in both the 1B5 (Ry53-/-) murine "dyspedic" myoblast cell line,
      which does not express any ryanodine receptor isoforms (Moore, R. A., Nguyen, H.,
      Galceran, J., Pessah, I. N., and Allen, P. D. (1998) J. Cell Biol. 140, 843-851),
      and C(2)C(12) cells, a myoblast cell line that expresses all three isoforms.
      Although 1B5 cells lack ryanodine binding, they bind tritiated inositol (1,4,5)
      trisphosphate. Both type 1 and type 3 inositol trisphosphate receptors were
      immuno-located in the nuclei of both cell types and were visualized by Western
      blot analysis. After stimulation with 47 mm K(+), inositol trisphosphate mass
      raised transiently in both cell types. Both fast calcium increase and slow
      propagated calcium signals were seen in C(2)C(12) myotubes. However, 1B5 myotubes
      (as well as ryanodine-treated C(2)C(12) myotubes) displayed only a long-lasting,
      non-propagating calcium increase, particularly evident in the nuclei. Calcium
      signals in 1B5 myotubes were almost completely blocked by inhibitors of the
      inositol trisphosphate pathway: U73122, 2-aminoethoxydiphenyl borate, or
      xestospongin C. Results support the hypothesis that inositol trisphosphate
      mediates slow calcium signals in muscle cell ryanodine receptors, having a role
      in their time course and propagation.

PMID- 11301325
TI  - Resting (basal) secretion of proteins is provided by the minor regulated and
      constitutive-like pathways and not granule exocytosis in parotid acinar cells.
AB  - Resting secretion of salivary proteins by the parotid gland is sustained in situ
      between periods of eating by parasympathetic stimulation and has been assumed to
      involve low level granule exocytosis. By using parotid lobules from ad libitum
      fed rats stimulated with low doses of carbachol as an in vitro analog of resting
      secretion, we deduce from the composition of discharged proteins that secretion
      does not involve granule exocytosis. Rather, it derives from two other acinar
      export routes, the constitutive-like (stimulus-independent) pathway and the minor
      regulated pathway, which responds to low doses of cholinergic or beta-adrenergic
      agonists (Castle, J. D., and Castle, A. M. (1996) J. Cell Sci. 109, 2591-2599).
      The protein composition collected in vitro mimics that collected from cannulated
      ducts of glands given low level stimulation in situ. Analysis of secretory
      trafficking along the two pathways of resting secretion has indicated that the
      constitutive-like pathway may pass through endosomes after diverging from the
      minor regulated pathway at a brefeldin A-sensitive branch point. The branch point
      is deduced to be distal to a common vesicular budding event by which both
      pathways originate from immature granules. Detectable perturbation of neither
      pathway in lobules was observed by wortmannin addition, and neither serves as a
      significant export route for lysosomal procathepsin B. These findings show that
      parotid acinar cells use low capacity, high sensitivity secretory pathways for
      resting secretion and reserve granule exocytosis, a high capacity, low
      sensitivity pathway, for massive salivary protein export during meals. An
      analogous strategy may be employed in other secretory cell types.

PMID- 11301326
TI  - ADP binding induces an asymmetry between the heads of unphosphorylated myosin.
AB  - Light chain phosphorylation is the key event that regulates smooth and non-muscle
      myosin II ATPase activity. Here we show that both heads of smooth muscle heavy
      meromyosin (HMM) bind tightly to actin in the absence of nucleotide, irrespective
      of the state of light chain phosphorylation. In striking contrast, only one of
      the two heads of unphosphorylated HMM binds to actin in the presence of ADP, and
      the heads have different affinities for ADP. This asymmetry suggests that
      phosphorylation alters the mechanical coupling between the heads of HMM. A model
      that incorporates strain between the two heads is proposed to explain the data,
      which have implications for how one head of a motor protein can gate the response
      of the other.

PMID- 11301327
TI  - Biosynthesis of riboflavin: studies on the mechanism of GTP cyclohydrolase II.
AB  - GTP cyclohydrolase II catalyzes the first committed reaction in the biosynthesis
      of the vitamin riboflavin. The recombinant enzyme from Escherichia coli is shown
      to produce 2,5-diamino-6-beta-ribosylamino-4(3H)-pyrimidinone 5'-phosphate and
      GMP at an approximate molar ratio of 10:1. The main product is subject to
      spontaneous isomerization affording the alpha-anomer. (18)O from solvent water is
      incorporated by the enzyme into the phosphate group of the 5-aminopyrimidine
      derivative as well as GMP. These data are consistent with the transient formation
      of a covalent phosphoguanosyl derivative of the enzyme. Subsequent ring opening
      of the covalently bound nucleotide followed by hydrolysis of the phosphodiester
      bond could then afford the pyrimidine type product. The hydrolysis of the
      phosphodiester bond without prior ring opening could afford GMP. The enzyme
      reaction is cooperative with a Hill coefficient of 1.3. Inhibition by
      pyrophosphate is competitive. Inhibition by orthophosphate is partially
      uncompetitive at low concentration and competitive at concentrations above 6 mm.

PMID- 11301328
TI  - Dual topology of the hepatitis B virus large envelope protein: determinants
      influencing post-translational pre-S translocation.
AB  - The large (L) envelope protein of the hepatitis B virus (HBV) has the peculiar
      capacity to form two transmembrane topologies via an as yet uncharacterized
      process of partial post-translational translocation of its pre-S domain across
      membranes. In view of a current model that predicts an HBV-specific channel
      generated during virion envelope assembly to enable pre-S translocation, we have
      examined parameters influencing L topogenesis by using protease protection
      analysis of wild-type and mutant L proteins synthesized in transfected cells. We
      demonstrate that contrary to expectation, all determinants, thought to be
      responsible for channel formation, are dispensable for pre-S reorientation. In
      particular, we observed that this process does not require (i) the helper
      function of the HBV S (small) and M (middle) envelope proteins, (ii) covalent
      dimer formation of envelope chains, or (iii) either of the three amphipathic
      transmembrane segments of L. Rather, the most hydrophobic transmembrane segment 2
      of L was identified as a vital topogenic determinant, essential and sufficient
      for post-translational pre-S translocation. Cell fractionation studies revealed
      that pre-S refolding and thus the dual topology of L is established at the
      endoplasmic reticulum (ER) membrane rather than at a post-ER compartment as
      originally supposed. Together our data provide evidence to suggest that the
      topological reorientation of L is facilitated by a host cell transmembrane
      transport machinery such as the ER translocon.

PMID- 11301329
TI  - Effect of ectopic expression of rat trefoil factor family 3 (intestinal trefoil
      factor) in the jejunum of transgenic mice.
AB  - To further examine the function of the trefoil factor family (TFF), the
      expression of which is up-regulated at sites of injury, we have produced
      transgenic mice that chronically express rat TFF3 within the jejunum (using a rat
      fatty acid-binding protein promoter). The expression of rat TFF3 was limited to
      the villi of the jejunum and had no effect on base-line morphology. Rat TFF3
      expression did result, however, in a reduced sensitivity to indomethacin (85
      mg/kg subcutaneously), which only caused a 29% reduction in villus height in
      transgenics versus 51% reduction in controls (p < 0.01). Indomethacin increased
      initial intestinal epithelial cell proliferation and migration, but the presence
      of rat TFF3 caused no additional change in proliferation (bromodeoxyuridine),
      cell migration ([(3)H]thymidine and bromodeoxyuridine), apoptosis (terminal
      deoxyuridine nucleotidyl nick end labeling), or E-cadherin immunostaining. In
      vitro studies following changes in resistance of intestinal strips in Ussing
      chambers (voltage-clamp technique) showed increased base-line resistance in the
      rat TFF3-expressing region (326 +/- 60 versus 195 +/- 48 ohm.cm(2) in controls, p
      < 0.05) and reduced the fall in resistance following HCl exposure by about 40% (p
      < 0.01). Overexpression of TFF3 stabilizes the mucosa against noxious agents,
      supporting its role in mucosal protection/repair. It may therefore provide a
      novel approach to the prevention and/or treatment of intestinal ulceration.

PMID- 11301330
TI  - Reactive chlorinating species produced by myeloperoxidase target the vinyl ether
      bond of plasmalogens: identification of 2-chlorohexadecanal.
AB  - Plasmalogens contain a vinyl ether bond linking the sn-1 aliphatic chain to the
      glycerol backbone of this predominant phospholipid molecular subclass, which is
      found in many mammalian tissues. The present study demonstrates that the vinyl
      ether bond of plasmalogens is a molecular target of the reactive chlorinating
      species produced by myeloperoxidase. Analysis by thin layer chromatography
      revealed that reactive chlorinating species produced by myeloperoxidase target
      the vinyl ether bond of the plasmalogen, lysoplasmenylcholine (1-O-hexadec-1'
      enyl-sn-glycero-3-phosphorylcholine), resulting in the production of a neutral
      lipid. Capillary gas chromatographic analyses demonstrated that the neutral lipid
      generated from lysoplasmenylcholine was neither hexadecanal nor did it contain
      masked hexadecanal (i.e. the vinyl ether) because the dimethyl acetal of
      hexadecanal produced by acid methanolysis derivatization was no longer present.
      Electrospray ionization mass spectrometry of the myeloperoxidase-generated
      neutral lipid product was consistent with the production of a 16-carbon fatty
      aldehyde containing one chlorine atom. Furthermore, proton NMR analysis indicated
      that this neutral lipid product was a 2-chloro-fatty aldehyde. Additional
      structural analysis of this neutral lipid by gas chromatography-mass spectrometry
      of the underivatized product as well as its pentafluorobenzyl oxime-derivative
      product was consistent with the neutral lipid being 2-chlorohexadecanal. The
      reactive chlorinating species, hypochlorous acid and chlorine gas, both attacked
      the vinyl ether bond of lysoplasmenylcholine resulting in the production of 2
      chlorohexadecanal. The production of 2-chlorohexadecanal was dependent on the
      presence of the plasmalogen masked aldehyde (i.e. the vinyl ether) in the
      substrate because the free fatty aldehyde, hexadecanal, was not converted to 2
      chlorohexadecanal by the reactive chlorinating species generated by
      myeloperoxidase. Taken together, the present studies demonstrate for the first
      time the targeting of the vinyl ether bond of plasmalogens by the reactive
      chlorinating species produced by myeloperoxidase resulting in the production of
      novel chlorinated fatty aldehydes.

PMID- 11301331
TI  - Trehalose accumulation during cellular stress protects cells and cellular
      proteins from damage by oxygen radicals.
AB  - The disaccharide trehalose, which accumulates dramatically during heat shock and
      stationary phase in many organisms, enhances thermotolerance and reduces
      aggregation of denatured proteins. Here we report a new role for trehalose in
      protecting cells against oxygen radicals. Exposure of Saccharomyces cerevisiae to
      a mild heat shock (38 degrees C) or to a proteasome inhibitor (MG132) induced
      trehalose accumulation and markedly increased the viability of the cells upon
      exposure to a free radical-generating system (H(2)O(2)/iron). When cells were
      returned to normal growth temperature (28 degrees C) or MG132 was removed from
      the medium, the trehalose content and resistance to oxygen radicals decreased
      rapidly. Furthermore, a mutant unable to synthesize trehalose was much more
      sensitive to killing by oxygen radicals than wild-type cells. Providing trehalose
      exogenously enhanced the resistance of mutant cells to H(2)O(2). Exposure of
      cells to H(2)O(2) caused oxidative damage to amino acids in cellular proteins,
      and trehalose accumulation was found to reduce such damage. After even brief
      exposure to H(2)O(2), the trehalose-deficient mutant exhibited a much higher
      content of oxidatively damaged proteins than wild-type cells. Trehalose
      accumulation decreased the initial appearance of damaged proteins, presumably by
      acting as a free radical scavenger. Therefore, trehalose accumulation in stressed
      cells plays a major role in protecting cellular constituents from oxidative
      damage.

PMID- 11301332
TI  - Glutathione-dependent binding of a photoaffinity analog of agosterol A to the C
      terminal half of human multidrug resistance protein.
AB  - MRP1 is a 190-kDa membrane glycoprotein that confers multidrug resistance (MDR)
      to tumor cells. MRP1 is characterized by an N-terminal transmembrane domain
      (TMD(0)), which is connected to a P-glycoprotein-like core region (DeltaMRP) by a
      cytoplasmic linker domain zero (L(0)). It has been demonstrated that GSH plays an
      important role in MRP1-mediated MDR. However, the mechanism by which GSH mediates
      MDR and the precise roles of TMD(0) and L(0) are not known. We synthesized
      [(125)I]11-azidophenyl agosterol A ([(125)I]azidoAG-A), a photoaffinity analog of
      the MDR-reversing agent, agosterol A (AG-A), to photolabel MRP1, and found that
      the analog photolabeled the C-proximal molecule of MRP1 (C(932-1531)) in a manner
      that was GSH-dependent. The photolabeling was inhibited by anticancer agents,
      reversing agents and leukotriene C(4). Based on photolabeling studies in the
      presence and absence of GSH using membrane vesicles expressing various truncated,
      co-expressed, and mutated MRP1s, we found that L(0) is the site on MRP1 that
      interacts with GSH. This study demonstrated that GSH is required for the binding
      of an unconjugated agent to MRP1 and suggested that GSH interacts with L(0) of
      MRP1. The photoanalog of AG-A will be useful for identifying the drug binding
      site within MRP1, and the role of GSH in transporting substrates by MRP1.

PMID- 11301333
TI  - High density lipoprotein (HDL) particle uptake mediated by scavenger receptor
      class B type 1 results in selective sorting of HDL cholesterol from protein and
      polarized cholesterol secretion.
AB  - High density lipoprotein (HDL) mediates reverse transport of cholesterol from
      atheroma foam cells to the liver, but the mechanisms of hepatic uptake and
      trafficking of HDL particles are poorly understood. In contrast to its accepted
      role as a cell surface receptor, scavenger receptor class B type 1 (SR-BI) is
      shown to be an endocytic receptor that mediates HDL particle uptake and
      recycling, but not degradation, in both transfected Chinese hamster ovary cells
      and hepatocytes. Confocal microscopy of polarized primary hepatocytes shows that
      HDL particles enter both the endocytic recycling compartment and the apical
      canalicular region paralleling the movement of SR-BI. In polarized epithelial
      cells (Madin-Darby canine kidney) expressing SR-BI, HDL protein and cholesterol
      undergo selective sorting with recycling of HDL protein from the basolateral
      membrane and secretion of HDL-derived cholesterol through the apical membrane.
      Thus, HDL particles, internalized via SR-BI, undergo a novel process of selective
      transcytosis, leading to polarized cholesterol transport. A distinct process not
      mediated by SR-BI is involved in uptake and degradation of apoE-free HDL in
      hepatocytes.

PMID- 11301334
TI  - The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia
      cells.
AB  - The ZIP superfamily of transporters plays important roles in metal ion uptake in
      diverse organisms. There are 12 ZIP-encoding genes in humans, and we hypothesize
      that many of these proteins are zinc transporters. In this study, we addressed
      the role of one human ZIP gene, hZIP1, in zinc transport. First, we examined
      (65)Zn uptake activity in K562 erythroleukemia cells overexpressing hZIP1. These
      cells accumulated more zinc than control cells because of increased zinc influx.
      Moreover, consistent with its role in zinc uptake, hZIP1 protein was localized to
      the plasma membrane. Our results also demonstrated that hZIP1 is responsible for
      the endogenous zinc uptake activity in K562 cells. hZIP1 is expressed in
      untransfected K562 cells, and the increase in mRNA levels found in hZIP1
      overexpressing cells correlated with the increased zinc uptake activity.
      Furthermore, hZIP1-dependent (65)Zn uptake was biochemically indistinguishable
      from the endogenous activity. Finally, inhibition of endogenous hZIP1 expression
      with antisense oligonucleotides caused a marked decrease in endogenous (65)Zn
      uptake activity. The observation that hZIP1 is the major zinc transporter in K562
      cells, coupled with its expression in many normal cell types, indicates that
      hZIP1 plays an important role in zinc uptake in human tissues.

PMID- 11301335
TI  - De-epoxidation of violaxanthin after reconstitution into different carotenoid
      binding sites of light-harvesting complex II.
AB  - In higher plants, the de-epoxidation of violaxanthin (Vx) to antheraxanthin and
      zeaxanthin is required for the pH-dependent dissipation of excess light energy as
      heat and by that process plays an important role in the protection against photo
      oxidative damage. The de-epoxidation reaction was investigated in an in vitro
      system using reconstituted light-harvesting complex II (LHCII) and a thylakoid
      raw extract enriched in the enzyme Vx de-epoxidase. Reconstitution of LHCII with
      varying carotenoids was performed to replace lutein and/or neoxanthin, which are
      bound to the native complex, by Vx. Recombinant LHCII containing either 2 lutein
      and 1 Vx or 1.6 Vx and 1.1 neoxanthin or 2.8 Vx per monomer were studied. Vx de
      epoxidation was inducible for all complexes after the addition of Vx de-epoxidase
      but to different extents and with different kinetics in each complex. Analysis of
      the kinetics indicated that the three possible Vx binding sites have at least
      two, and perhaps three, specific rate constants for de-epoxidation. In
      particular, Vx bound to one of the two lutein binding sites of the native
      complex, most likely L1, was not at all or only at a slow rate convertible to Zx.
      In reisolated LHCII, newly formed Zx almost stoichiometrically replaced the
      transformed Vx, indicating that LHCII and Vx de-epoxidase stayed in close contact
      during the de-epoxidation reactions and that no release of carotenoids occurred.

PMID- 11301336
TI  - Functional analysis of the chimpanzee and human apo(a) promoter sequences:
      identification of sequence variations responsible for elevated transcriptional
      activity in chimpanzee.
AB  - Lp(a) concentrations vary considerably among individuals and are primarily
      determined by the apo(a) gene locus. We have previously shown that mean plasma
      Lp(a) levels in the chimpanzee are significantly higher than those observed in
      humans (Doucet, C., Huby, T., Chapman, J., and Thillet, J. (1994) J. Lipid Res
      35, 263-270). To evaluate the possibility that this difference may result from a
      high level of expression of chimpanzee apo(a), we cloned and sequenced 1.4
      kilobase (kb) of the 5'-flanking region of the gene and compared promoter
      activity to that of its human counterpart. Sequence analysis revealed 98%
      homology between chimpanzee and human apo(a) 5' sequences; among the differences
      observed, two involved polymorphic sites associated with Lp(a) levels in humans.
      The TTTTA repeat located 1.3 kb 5' of the apo(a) gene, present in a variable
      number of copies (n = 5-12) in humans, is uniquely present as four copies in the
      chimpanzee sequence. The second position concerns the +93 C>T polymorphism that
      creates an additional ATG start codon in the human apo(a) gene, thereby impairing
      translation efficiency. In chimpanzee, this position did not appear polymorphic,
      and a base difference at position +94 precluded the presence of an additional
      ATG. In transient transfection assays, the chimpanzee apo(a) promoter exhibited a
      5-fold elevation in transcriptional activity as compared with its human
      counterpart. This marked difference in activity was maintained with either 1.4 kb
      of 5' sequence or the minimal promoter region -98 to +141 of the human and
      chimpanzee apo(a) genes. Using point mutational analyses, nucleotides present at
      positions -3, -2, and +8 (relative to the start site of transcription) were found
      to be essential for the high transcription efficiency of the chimpanzee apo(a)
      promoter. High transcriptional activity of the chimpanzee apo(a) gene may
      therefore represent a key factor in the elevated plasma Lp(a) levels
      characteristic of this non-human primate.

PMID- 11301337
TI  - XRCC2 is a nuclear RAD51-like protein required for damage-dependent RAD51 focus
      formation without the need for ATP binding.
AB  - The human XRCC2 gene was recently identified by its ability to complement a
      hamster cell line, irs1, which is sensitive to DNA-damaging agents and shows
      genetic instability. The XRCC2 protein is highly conserved in mammalian species
      and has structural features, including a putative ATP-binding domain (P-loop),
      consistent with membership of the RecA/RAD51 family of recombination-repair
      proteins. We show that a hybrid XRCC2-green fluorescent protein, which was found
      to be functional by complementation, localizes to the nucleus. We have
      established a functional link between XRCC2 and RAD51 by looking at damage
      dependent RAD51 focus formation in the irs1 cell line. Little or no formation of
      RAD51 foci occurred in irs1. This effect was specific to the loss of XRCC2
      because transfection of the gene into irs1 restored normal levels of focus
      formation. Surprisingly, XRCC2 genes carrying site-specific mutations in P-loop
      residues were found to be able to complement the XRCC2-deficient irs1 line for a
      number of different end points. We conclude that XRCC2 is important in the early
      stages of homologous recombination in mammalian cells to facilitate RAD51
      dependent recombination repair but that it does not make use of ATP binding to
      promote this function.

PMID- 11301338
TI  - Trihelix DNA-binding protein with specificities for two distinct cis-elements:
      both important for light down-regulated and dark-inducible gene expression in
      higher plants.
AB  - The DE1 sequence is a cis-regulatory element necessary and sufficient for light
      down-regulated and dark-inducible expression of the pea GTPase pra2 gene. This
      sequence does not show any sequence similarity to the previously reported ones
      involved in light-regulated gene expression. A one-hybrid screen isolated a cDNA
      encoding a DNA-binding protein, named DF1, with specificity for the DE1 sequence
      5'-TACAGT. DF1 has domains similar to the trihelix DNA-binding domain found in
      the GT-1 and GT-2 proteins, which are plant transcription factors. The DE1
      binding domain of DF1 is most similar to the carboxyl-terminal trihelix domain of
      the rice GT-2 protein with specificity for the GT2 sequence 5'-GGTAATT, which is
      also necessary for dark-inducible expression of the rice phyA gene. An
      electrophoretic mobility shift assay showed that this DNA-binding domain
      specifically binds to two types of DNA sequences, DE1 and GT2. Additionally,
      using DF1/GT-1 chimeras, we show that the second and third helices of the
      trihelix DNA-binding domain of DF1 are responsible for this dual DNA binding
      specificity. Our results show that DF1 has specificity for the two distinct cis
      regulatory elements, both important for light down-regulated and dark-inducible
      gene expression in higher plants.

PMID- 11301339
TI  - Multimeric structure of the secreted meprin A metalloproteinase and
      characterization of the functional protomer.
AB  - Meprin A secreted from kidney and intestinal epithelial cells is capable of
      cleaving growth factors, extracellular matrix proteins, and biologically active
      peptides. The secreted form of meprin A is a homo-oligomer composed of alpha
      subunits, a multidomain protease of 582 amino acids coded for near the major
      histocompatibility complex of the mouse and human genome. Analyses of the
      recombinant homo-oligomeric form of mouse meprin A by gel filtration,
      nondenaturing gel electrophoresis, and cross-linking (with disuccinimidyl
      suberate or N-(4-azido-2,3,5,6-tetraflourobenzyl)-3-maleimidylpropionamide)
      indicate that the secreted enzyme forms high molecular weight multimers, with a
      predominance of decamers. The multimers are composed of disulfide-linked dimers
      attached noncovalently by interactions involving the meprin, A5 protein, receptor
      protein-tyrosine phosphatase mu (MAM) domain. The active protomer is the
      noncovalently linked dimer. Linkage of active protomers by disulfide-bonds
      results in an oligomer of approximately 900 kDa, which is unique among proteases
      and distinguishes meprin A as the largest known secreted protease. Electron
      microscopy revealed that the protein was present in two states, a crescent-shaped
      structure and a closed ring. It is concluded from this and other data that the
      covalent attachment of the protomers enables noncovalent associations of the
      native enzyme to form higher oligomers that are critical for hydrolysis of
      protein substrates.

PMID- 11301340
TI  - Unraveling the mechanism of the vesicle transport ATPase NSF, the N
      ethylmaleimide-sensitive factor.

PMID- 11301341
TI  - Comparison of the WHO/ISUP classification and cytokeratin 20 expression in
      predicting the behavior of low-grade papillary urothelial tumors. World/Health
      Organization/Internattional Society of Urologic Pathology.
AB  - It has not been possible to identify those low-grade papillary transitional cell
      bladder tumors that will recur based on conventional histopathologic assessment.
      Both the new World Health Organization/International Society of Urologic
      Pathology (WHO/ISUP) classification of transitional cell papillary neoplasms and
      the pattern of tumor cytokeratin 20 (CK20) immunostaining have been suggested as
      means of improving prognostication in low-grade transitional cell tumors. Forty
      nine low-grade, noninvasive papillary transitional cell tumors were identified
      for the period between 1984 and 1993. The recently described WHO/ISUP
      classification was applied, and the tumors were classified histologically as
      papilloma, papillary neoplasm of low malignant potential (LMP) or low-grade
      papillary carcinoma. After CK20 immunostaining, the expression pattern in the
      tumor was classified as normal (superficial) or abnormal. Of 49 tumors, 20 were
      classified as papillary neoplasms of LMP and five of these patients (25%)
      experienced a recurrence. Of 29 tumors classified as low-grade papillary
      carcinoma, 14 (48.2%) recurred. In 46 of 49 cases, the CK20 immunostaining could
      be evaluated. Sixteen tumors showed normal (superficial) pattern of CK20
      expression, and four (25%) of these patients experienced a recurrence. In
      contrast, of 30 patients with abnormal CK20 staining of their tumors, 15 (50%)
      patients had one or more recurrences. In this study, papillary neoplasms of LMP
      (as per the WHO/ISUP classification system) had a lower recurrence rate than low
      grade papillary transitional cell carcinoma. Similarly low-grade urothelial
      tumors showing a normal CK20 expression pattern recurred less frequently than
      tumors with an abnormal pattern of CK20 staining. Neither of these differences
      was statistically significant, and recurrences were observed in 20% of patients
      whose tumors were both classified as papillary neoplasms of LMP and showed normal
      CK20 immunostaining; thus they do not allow a change in our current management of
      patients with low-grade papillary urothelial tumors, with close follow-up for all
      patients.

PMID- 11301342
TI  - Frequent loss of heterozygosity at 1p36.3 and p73 abnormality in parathyroid
      adenomas.
AB  - Although 1p is one of the most common loci showing loss of heterozygosity (LOH)
      in primary parathyroid adenoma, fine mapping has not been previously examined. In
      this study, we analyzed LOH in 32 primary parathyroid adenomas using five
      microsatellite markers at 1p36 (proximal-D1S507-D1S450-D1S2893-D1S468-D1S243
      distal). All cases were heterozygous for at least one marker. The frequency of
      LOH varied from 41.2% (D1S468) to 7.1% (D1S507) among the different markers. LOH
      was detected consistently in a group of nine adenomas (28.1%, 9/32). A single
      region (7 cM) showing a consistent LOH at 1p36.3 was obtained that was flanked
      distally by D1S468 and proximally by D1S2893. Because the p73 gene is localized
      within this region and acts as a tumor suppressor gene, we examined the possible
      involvement of p73 in the development of parathyroid tumor. Allelic loss of p73
      was identified in four adenomas (25%, 4/16 informative cases) that were all from
      the group of the nine adenomas with LOH, but somatic mutation was not detected in
      the remaining allele. At the StyI polymorphism of Exon 2, four of the six
      adenomas with LOH at 1p36 were heterozygous and expressed the GC allele. Of the
      six heterozygous adenomas without LOH, 4 showed biallelic and 2 monoallelic
      expressions (GC allele). All adenomas mainly expressed the p73alpha isoform. p73
      protein was observed in five of the six adenomas with LOH and in two of the six
      adenomas without LOH. There were no differences in p73 protein levels between the
      samples with and without LOH. In conclusion, a candidate gene for parathyroid
      tumorigenesis is present within a 7-cM region at 1p36.3, however p73 is unlikely
      to be the target of the LOH at 1p36.3.

PMID- 11301343
TI  - Human papillomavirus infection, centrosome aberration, and genetic stability in
      cervical lesions.
AB  - DNA replication and centrosome duplication have to be strictly synchronized to
      guarantee genomic stability. p53, pRb, cyclin E, and cyclin A are reported to be
      involved in the synchronizing process. We investigated the relationship between
      papillomavirus infection, centrosome aberration and aneuploidy during genesis of
      cervical carcinoma. The number of centrosomes found in cells from normal cervical
      epithelium (n = 5), condyloma acuminata (n = 5), cervical intraepithelial
      neoplasia (CIN) I, II, and III (n = 14) and invasive cervical carcinoma (n = 5)
      was analyzed by gamma tubulin immunofluorescence staining. The nuclear DNA
      content was investigated by image cytometry and human papillomavirus (HPV)
      infection was determined by polymerase chain reaction. Normal epithelia and
      condyloma acuminata showed cells with one or two centrosomes, whereas CIN lesions
      showed cells with an increasing number of centrosomes. This abnormality was found
      to be lowest in CIN I lesions, increased with advancing grade of CIN and was
      highest in lesions of invasive carcinomas. In parallel, an increasing number of
      cells with aberrant DNA content was seen. All carcinomas and all except one of
      the CIN III lesions showed aneuploidy. Three CIN II cases were aneuploid and two
      cases with CIN I were tetraploid. Normal epithelia and condyloma acuminata showed
      diploidy. All invasive carcinomas and lesions with CIN were positive for high
      risk HPV types 16, 18, or 31, except one invasive carcinoma and one CIN II lesion
      positive for universal primers only. Three condyloma acuminata were HPV 16
      positive and one HPV 6-positive. The results suggest that high-risk HPV infection
      is correlated to a progressive numerical disturbance of centrosome replication
      followed by progressive chromosomal aberrations in CIN lesions and invasive
      carcinomas.

PMID- 11301344
TI  - Reassessment of lymphocytic atypia in the diagnosis of mycosis fungoides.
AB  - The manifestations of mycosis fungoides in its early stage may mimic clinically
      and histologically those of many benign inflammatory dermatoses. Therefore, the
      diagnosis of mycosis fungoides remains a major challenge for dermatologists and
      dermatopathologists. For many years, it has been proposed that atypical
      lymphocytes within the epidermis constitute one of the diagnostic features in
      mycosis fungoides. Presence of dermal atypical lymphocytes remains controversial
      as a diagnostic criterion. We reassessed the feasibility of applying lymphocytic
      atypia within epidermis and dermis as diagnostic criteria discriminating between
      mycosis fungoides and spongiotic dermatitis. Thirty cases of mycosis fungoides
      and 30 cases of spongiotic dermatitis were retrieved from archival hematoxylin
      and eosin-stained histologic sections. Punch biopsy sections were examined by
      light microscopy; epidermal and dermal lymphocytes were photographed at 1000x
      (oil immersion). A total of 92 ektachrome slides (35 mM) were developed, coded,
      and ordered randomly. For each slide, cells were interpreted as typical or
      atypical lymphocytes by seven pathologists. Atypical epidermal lymphocytes were
      judged to be present in 9 +/- 2 out of 16 (56%) cases of mycosis fungoides
      photographed as compared with 8 +/- 3 out of 16 (50%) in spongiotic dermatitis.
      Dermal lymphocytic atypia was thought to be present in 14 +/- 6 out of 30 (47%)
      patients with mycosis fungoides. Thirteen +/- 6 out of 30 (43%) patients with non
      mycosis fungoides also displayed dermal lymphocytic atypia. No statistical
      significance was observed in these comparisons (t test, P >.05). Furthermore,
      atypia of lymphocytes was deemed to be present in 41, 38, 59, 70, 23, 47, and 40
      out of 92 slides examined by the investigators, suggesting that observer
      variation is a very significant factor in our present study. We conclude that it
      is not possible to distinguish mycosis fungoides from spongiotic dermatitis
      merely based on lymphocytic atypia within epidermis or dermis.

PMID- 11301345
TI  - Expression of the sodium iodide symporter and thyroglobulin genes are reduced in
      papillary thyroid cancer.
AB  - Altered expression of the gene encoding the sodium iodine symporter (NIS) may be
      an important factor that leads to the reduced iodine accumulation characteristic
      of most benign and malignant thyroid nodules. Both up- and down-regulation of NIS
      gene expression have been reported in thyroid cancer using several different
      methods. The goal of the present study was to accurately identify alterations in
      NIS gene expression in benign and malignant thyroid nodules using an accurate
      real-time quantitative RT-PCR assay system. Total RNA was prepared from 18 benign
      thyroid nodules, 20 papillary thyroid cancers, and 23 normal thyroid samples from
      38 subjects. Quantitative RT-PCR was used to measure NIS and thyroglobulin (TG)
      mRNA expression in normal thyroid tissue and in each nodular tissue sample.
      Papillary thyroid cancer samples had significantly lower NIS mRNA expression (72
      +/- 41 picogram equivalents [pg Eq]), than did benign nodules (829 +/- 385 pg
      Eq), or normal tissues (1907 +/- 868 pg Eq, P = 0.04). Most important, in the
      paired samples, NIS gene expression was decreased in each papillary thyroid
      cancer compared with normal tissue (69% median decrease; range, 40-96%; P =
      .013). Eleven of the 12 benign nodules also demonstrated lower NIS gene
      expression than the normal tissue (49% decrease; range, 2-96%; P = .04). Analysis
      of the paired samples demonstrated that Tg mRNA expression was significantly
      lower in each of the thyroid cancer samples than in corresponding normal tissue
      (759 +/- 245 pg Eq vs. 1854 +/- 542 pg Eq, P = .03). We have demonstrated a
      significant decrement in NIS gene expression in all papillary thyroid cancers and
      in over 90% of benign nodules examined compared with adjacent normal thyroid
      tissue, using a highly accurate quantitative RT-PCR technique. Similarly, thyroid
      cancers demonstrated significantly lower TG mRNA expression than corresponding
      normal thyroid. Reduced NIS expression may be an important factor in the
      impairment of iodine-concentrating ability of neoplastic thyroid tissues.

PMID- 11301346
TI  - Characterization of NF-kappaB expression in Hodgkin's disease: inhibition of
      constitutively expressed NF-kappaB results in spontaneous caspase-independent
      apoptosis in Hodgkin and Reed-Sternberg cells.
AB  - Although the neoplastic cells of classical Hodgkin's disease (CHD) demonstrate
      high levels of constitutively active nuclear NF-kappaB, the precise physiologic
      and clinical significance of NF-kappaB expression is currently undefined.
      Expression of active NF-kappaB p65(Rel A) was evaluated in patient samples of CHD
      and nodular lymphocyte predominance Hodgkin's disease. The action of the chemical
      NF-kappaB inhibitors gliotoxin and MG132 and the effect of NF-kappaB inhibition
      utilizing an adenovirus vector carrying a dominant-negative IkappaBalpha mutant
      (Ad5IkappaB) were then demonstrated in CHD cell lines (L428, KMH2, and HS445).
      Hodgkin and Reed-Sternberg (HRS) cells from all patient and cell line specimens
      showed strong immunopositivity for active p65(Rel A). Expression was also seen in
      lymphocytic/histiocytic cells from all cases of nodular lymphocyte predominance
      Hodgkin's disease. After chemical NF-kappaB inhibition, p65(Rel A) was
      significantly reduced in nuclear extracts from cultured HRS cells as revealed by
      electrophoretic mobility shift assays. Furthermore, chemical NF-kappaB inhibition
      resulted in time- and concentration-dependent apoptosis in HRS cells. With the
      exception of MG132-induced apoptosis in HS445, apoptosis by chemical NF-kappaB
      inhibition was not significantly altered by preincubation with various caspase
      inhibitors (z-DQMD-FMK, z-DEVD-FMK, z-VAD-FMK, z-VEID-FMK, and z-IETD-FMK).
      Regardless of the chemical inhibitor used, no significant change in caspase-3
      functional activity was found in CHD cell lines. HRS cells infected with
      Ad5IkappaB also showed a marked increase in spontaneous apoptosis compared with
      wild type adenovirus-infected and control cells. Overall, the inhibition of
      active NF-kappaB in HRS cells resulting in spontaneous caspase-independent
      apoptosis demonstrates a critical role for NF-kappaB in HRS cell survival and
      resistance to apoptosis.

PMID- 11301347
TI  - The tumor-associated gene HMGIC is expressed in normal and osteoarthritis
      affected synovia.
AB  - Chromosomal rearrangements involving chromosome bands 12q13-15 are very frequent
      findings in benign solid tumors, and recently, the primary molecular target for
      these aberrations was identified as the gene HMGIC. However, mutations in this
      gene have also been observed in nonneoplastic tissues. In a previous study, we
      reported breakpoints within HMGIC of synovia affected by osteoarthritis (OA) in
      two cases with 12q15 aberrations. To analyze further the role of HMGIC in this
      disease, we have performed cytogenetic, fluorescent in situ hybridization (FISH),
      RNA, and protein expression analyses on synovial samples from patients with OA
      and individuals without signs of the disorder. Cytogenetic analysis of short-term
      cultured cells revealed clonal 12q13-15 aberrations in 2/36 cases of OA synovia
      and no rearrangement in any of the five controls. With FISH analysis, it was
      shown that the chromosomal breakpoints in the two aberrant cases were located
      outside the HMGIC locus. In contrast, at RNA and protein expression analyses, OA
      affected as well as normal synovia displayed transcription and translation of the
      gene. We also analyzed whether immunoreactivity for HMGIC was associated with the
      proliferation-specific antigen Ki-67, but no correlation between the staining
      patterns of these proteins was observed. From the results of the present study,
      it is evident that expression of HMGIC cannot simply be considered a sign of
      neoplasia or an effect of proliferation.

PMID- 11301348
TI  - Expression of cysteine proteinases cathepsins B and K and of cysteine proteinase
      inhibitor cystatin C in giant cell tumor of tendon sheath.
AB  - The expression of cysteine proteinases cathepsins B and K and of the endogenous
      inhibitor of cysteine proteinases, cystatin C, was investigated in tissue
      specimens of patients with giant cell tumor of tendon sheath (GCTTS). Expression
      of both enzymes was examined by immunohistochemistry in tissue specimens of 14
      patients with GCTTS. Applying double-labeling techniques, the coexpression of
      cathepsin B and its major endogenous inhibitor cystatin C was additionally
      studied. Cells expressing the respective proteins were further characterized with
      the macrophage markers HAM56 and anti-CD68 (clone PG-M1). Cathepsin B could be
      detected in numerous HAM56-positive mononuclear cells (MC), but only in very few
      giant cells (GC). In contrast, cathepsin K was predominantly identified in GC
      that were also strongly immunoreactive for cystatin C and CD68. Coexpression of
      cathepsin B and cystatin C occurred only in a few MC. The strong expression of
      both cathepsin B and K suggests that in GCTTS, bone erosion might be mediated not
      only by pressure of the proliferative tissue, but also by matrix-degrading
      cysteine proteinases. Because previous studies showed that osteoclasts express
      high levels of CD68, cathepsin K, and cystatin C but not of cathepsin B, our
      study contributes to the view that GC of GCTTS and osteoclasts are closely
      associated.

PMID- 11301349
TI  - Highly proliferative fibroblasts forming fibrotic focus govern metastasis of
      invasive ductal carcinoma of the breast.
AB  - We have already reported that invasive ductal carcinomas (IDCs) with fibrotic
      focus (FF) have more aggressive characteristics than those without FF. FF is
      composed of a mixture of fibroblasts and various amounts of collagen fibers,
      suggesting that highly proliferative fibroblasts forming FF increase the
      malignant potential of IDCs with FF. The purpose of this study was to examine
      whether there is a difference of proliferative activity of fibroblasts forming
      and not forming FF, which plays an important role in the tumor progression of
      IDCS: Two hundred three consecutive cases of IDC of the breast surgically treated
      at the National Cancer Center Hospital East formed the basis for this study. The
      proliferative activity of the fibroblasts forming the FF was
      immunohistochemically evaluated by using mouse MIB-1 monoclonal antibody against
      Ki-67 antigen. The MIB-1 labeling index (LI) is the percentage of fibroblasts
      forming FF that have positively stained nuclei, and 300 fibroblasts were counted
      in each FF. The significance of the proliferative activity of fibroblasts forming
      FF with regard to lymph node metastasis (LNM) or distant-organ metastasis (DOM)
      was compared with well-known prognostic parameters. Multivariate analysis
      demonstrated that high MIB-1 LI of fibroblasts forming FF significantly increased
      the relative risk of LNM and the hazard rate of DOM (P < .001 and P = .009). The
      present study indicated that the metastatic ability of IDCs with FF is highly
      dependent on the proliferative activity of the fibroblasts forming FF.

PMID- 11301350
TI  - Immunohistochemical diagnosis of papillary thyroid carcinoma.
AB  - In thyroid, the diagnosis of papillary carcinoma (PC) is based on nuclear
      features; however, identification of these features is inconsistent and
      controversial. Proposed markers of PC include HBME-1, specific cytokeratins (CK)
      such as CK19, and ret, the latter reflecting a ret/PTC rearrangement. We applied
      immunohistochemical stains to determine the diagnostic accuracy of these three
      markers. Formalin-fixed, paraffin-embedded tissue from 232 surgically resected
      thyroid nodules included 40 hyperplastic nodules (NH), 35 follicular adenomas
      (FA), 138 papillary carcinomas (PC; 54 classical papillary tumors and 84
      follicular variant papillary carcinomas [FVPC]), 4 follicular carcinomas (FC), 6
      insular carcinomas (IC), 7 Hurthle cell carcinomas (HCC), and 2 anaplastic
      carcinomas (AC). HBME-1 and ret were negative in all NH and FA; some of these
      exhibited focal CK19 reactivity in areas of degeneration. Half of the FC and AC
      exhibited HBME-1 staining but no positivity for CK19 or ret. In PC, 20% of cases
      stained for all three markers. Classical PC had the highest positivity with
      staining for HBME-1 in 70%, CK19 in 80%, and ret in 78%. FVPC were positive for
      HBME-1 in 45%, for CK19 in 57%, and for ret in 63%; only 7 FVPC were negative for
      all three markers. The six IC exhibited 67% staining for HBME-1 and 50%
      positivity for CK19 and ret. The seven HCC had 29% positivity for HBME-1 and
      CK19, and 57% positivity for ret. This panel of three immunohistochemical markers
      provides a useful means of diagnosing PC. Focal CK19 staining may be found in
      benign lesions, but diffuse positivity is characteristic of PC. HBME-1 positivity
      indicates malignancy but not papillary differentiation. Only rarely are all three
      markers negative in PC; this panel therefore provides an objective and
      reproducible tool for the analysis of difficult thyroid nodules.

PMID- 11301351
TI  - H-ras oncogene mutation in dedifferentiated chondrosarcoma: polymerase chain
      reaction-restriction fragment length polymorphism analysis.
AB  - Dedifferentiated chondrosarcomas, which are known for their poor prognosis, are
      characterized by conventional chondrosarcoma with high-grade anaplastic
      components. Activating mutations in ras genes are a common genetic abnormality in
      human malignancies. The presence of point mutations at codons 12 and 13 of the H
      ras gene was studied in 20 formalin-fixed paraffin-embedded chondrosarcomas,
      comprising 11 cases of conventional chondrosarcoma (six Grade 1 cases and five
      Grade 2 cases) and nine cases of dedifferentiated chondrosarcoma, using
      polymerase chain reaction-restriction fragment length polymorphism and direct
      sequencing analysis. H-ras mutations were only seen in two out of the nine cases
      of dedifferentiated chondrosarcoma (2/9, 22%) and they were not seen in any of
      the cases of conventional chondrosarcoma (0/11, 0%). Dedifferentiated
      chondrosarcomas had a worse prognosis than conventional chondrosarcomas (P <
      .01); among the patients with dedifferentiated chondrosarcomas, those with H-ras
      mutation (n = 2) tended to have a worse prognosis than those without (n = 7),
      although the difference was not statistically significant (P = 0.068). Our
      results would seem to suggest that H-ras mutation may occur during the course of
      dedifferentiation and may also have some effect on malignant potential.

PMID- 11301352
TI  - Does exhaustive search for microcalcifications improve diagnostic yield in
      stereotactic core needle breast biopsies?
AB  - Stereotactic core needle biopsy (SCNB) of the breast is a cost-effective
      alternative to needle localization biopsy for the diagnosis of mammographic
      calcifications. We questioned whether an exhaustive search for calcium in the
      small samples obtained in SCNB yields more diagnostic information than that
      obtained with examination of a standard number of sections. We retrospectively
      reviewed 168 specimens from 123 patients with mammographic calcifications,
      including cases in which radiographic suspicion ranged from low to high.
      Microcalcifications were identified on three initial levels in 112 specimens.
      Additional sections were examined in 50 specimens. The final diagnosis differed
      from the diagnosis based on three levels in 11/50 cases (22%). In 6/50 (12%),
      complete sectioning yielded a specific diagnosis. The increase in technical cost
      associated with the additional levels was 414% per case. We conclude that
      exhaustive searching for microcalcifications in SCNB yields a small increase in
      specific diagnostic information and a high technical cost. In individual cases,
      the additional information may be critical for appropriate patient management.

PMID- 11301353
TI  - Follicular dendritic cell tumor of the liver: a clinicopathologic and Epstein
      Barr virus study of two cases.
AB  - Two cases of hepatic follicular dendritic cell (FDC) tumor are described. Both
      patients were female, aged 57 and 51 years. They presented with epigastralgia or
      abdominal fullness and weight loss. The first patient refused surgical resection.
      She developed progressive polyclonal gammopathy and then bilateral purpura over
      the legs. Skin biopsy revealed leukocytoclastic vasculitis with granular vascular
      deposits of IgA and C3. The second patient had marked peripheral blood and tissue
      eosinophilia. The histological diagnosis was confirmed by positive staining for
      CD21 and CD23. The stromal lymphocytes were predominantly composed of CD3(+)and
      CD8(+) cells. In situ hybridization for EBER showed a positive nuclear signal in
      tumor cells but not in inflammatory cells. Polymerase chain reaction
      amplification for Exon 3 of the latent membrane protein-1 (LMP-1) gene showed a
      characteristic 30-bp deletion between nucleotides 168282 and 168253,
      corresponding to the B95-8 sequence. The unique clinicopathological features of
      our cases have not been reported for FDC tumors before. The clinical significance
      of the 30-bp deletion in Exon 3 of the LMP-1 gene in FDC tumor of the liver
      warrants further investigation.

PMID- 11301354
TI  - Aspiration cytopathology of metastatic mucinous papillary thyroid carcinoma.
AB  - The light microscopic histopathology and cytopathology of papillary thyroid
      carcinoma (PTC) and its variants is amply depicted in reviews, books, and book
      chapters. One of the changes in PTC, however, that is infrequently discussed or
      illustrated in the literature is that of mucinous metaplasia. In the aspiration
      cytopathology literature, we are aware of only a rare report of PTC exhibiting
      extensive mucinous metaplasia. We present an example correlating the
      histopathology and fine needle aspiration cytopathology of a PTC that had
      metastasized on several separate occasions to cervical lymph nodes, and in the
      process demonstrated mucinous transformation. Without a prior history of PTC, the
      aspirate smears and tissue sections could have been mistaken easily for
      metastatic clear cell carcinoma of non-thyroidal origin. Mucinous metaplasia
      represents an extremely uncommon, but nonetheless potential, pitfall in the
      aspiration cytopathology and histopathology of metastatic PTC.

PMID- 11301356
TI  - Good News/Bad News.

PMID- 11301355
TI  - Correspondence Re: Demarchi LMMF, Reis MM, Palomina SAP, Farhat C, Takagaki TY,
      Beyruti R, et al. Prognostic values of stromal proportion and PCNA, Ki-67, and
      p53 proteins in patients with resected adenocarcinoma of the lung. MOD Pathol
      2000; 13:511-20.

PMID- 11301357
TI  - [3D-ct angiography of cerebral arteriovenous malformation in children].

PMID- 11301358
TI  - [Spinal cord function and ischmic injury].

PMID- 11301359
TI  - [Abnormalities of the p53, N-ras, DCC and FLT-3 genes in myelodysplastic
      syndromes].
AB  - The molecular mechanism of carcinogenesis is a multistep process that is
      characterized by both activation of oncogenes and inactivation of tumor
      suppressor genes. In the present study, mutations of N-ras, p53 and FMS-like
      tyrosine kinase 3 (FLT-3) genes and loss of expression of the deleted in
      colorectal carcinoma (DCC) gene were analyzed in 59 patients with myelodysplastic
      syndromes (MDS). Mutations of N-ras, p53, and FLT-3 genes were detected in 7, 7,
      1 of the 59 patients with MDS, respectively. Loss of DCC expression was detected
      in 16 patients. Type of MDS patients with N-ras mutation were all refractory
      anemia with excess of blasts in transformation (RAEB-T). Abnormalities of p53 and
      DCC genes were significantly associated with survival time (p< 0.02, p< 0.004,
      respectively).

PMID- 11301360
TI  - The efficacy of ununited tibial fracture treatment using pulsing electromagnetic
      fields: relation to biological activity on nonunion bone ends.
AB  - Thirty ununited tibial fractures with a median time since injury of 18+/-9 months
      were treated by electrical stimulation using pulsing electromagnetic field
      therapy. Union was achieved in 25 cases (83.3%) in a median interval of 8.6+/-3.2
      months. Patient age and gender, the presence of surgical hardware, length of
      disability, and the number of surgical procedures did not affect the outcome.
      Ununited fractures that appeared to be hypertrophic or sclerotic type
      radiographically, indicating a good blood supply to the bone ends, all healed.
      Treatment failures occurred only among lesions with a poor blood supply, and in
      necrotic or defective radiopraphic types. Pulsing electromagnetic field therapy
      is an effective treatment for ununited tibial fractures with good blood supply to
      the bone ends.

PMID- 11301361
TI  - [The protective effect of hepatocyte growth-promoting factor (pHGF) against
      carbon tetrachloride-induced acute liver injury in rats. II. Protective effects
      on cell membrane injury].
AB  - To examine the protective effects of hepatocyte growth-promoting factor (pHGF)
      against carbon tetrachloride (CCl4) -induced acute liver injury in rats, the
      pathological changes were observed by light and electron microcopy, and the serum
      GOT and GPT levels were measured. Acute liver injury was produced by the
      injection of CCl4 (2ml/kg BW) in two groups of animals, of which one received
      pHGF (300 microg/kg BW) via the tail vein after 4 hrs. In the group treated with
      CCl4 alone, serum GOT and GPT were significantly elevated (1280+/-228 and 187+/
      73 IU/l, respectively) 6 hrs after injection, indicating the induction of liver
      injury by CCl4. They reached a peak (3836+/-654 and 1022+/-230 IU/l,
      respectively) at 48 hrs and declined thereafter, but did not completely recover
      after 72 hrs. PAS-negative cells were observed around the central veins after 6
      hrs and most of the hepatocytes were PAS-negative at 12 hrs. PAS-positive cells
      began to appear and increased in number after 24 hrs. There were scarcely any PAS
      negative cells remaining in the lobules after 72 hrs. In the group treated with
      CCl4 followed by pHGF, serum GOT and GPT levels were significantly lower than in
      the CCl4-treated group, and abundant PAS-positive hepatocytes were observed.
      Also, all hepatocytes were PAS-positive (as in normal liver) after 72 hrs.
      Administration of pHGF resulted in a decrease in the ultrastructural changes in
      rats with CCl4-induced liver injury such as vacuolation, cisternae formation and
      dilatation of the rough endoplasmic reticulum. These results suggest that pHGF
      acts to stabilize cell membranes, thereby providing protection against CCl4
      induced hepatic injury.

PMID- 11301362
TI  - Serum and synovial fluid levels of chondroitin sulfate in patients with
      osteoarthritis of the knee joint.
AB  - We measured serum and synovial fluid levels of chondroitin sulfate (CS) in
      patients with osteoarthritis (OA) of the knee joint to clarify whether CS levels
      differ in various stages of OA, and whether measurement of CS levels is useful in
      evaluating the pathology of OA. The study population was 117 OA patients and 23
      healthy young volunteers. Synovial fluid was obtained from 69 of 117 OA patients.
      The mean serum level of C4S in all of the OA patients was significantly higher
      than that in the controls (p< 0.05). However, there was little difference between
      respective OA stages. A small amount of serum C6S (0.2 to 0.6 nmol/ml) was
      detected in 31.6% of the OA patients and in 26.1%of the control subjects. The
      mean serum C0S level in all OA patients was significantly higher than that in the
      controls (p< 0.01). However no significant difference was found between
      respective OA stages. As for synovial fluid CS, the C4S level in the early stage
      of OA tended to be higher than that in the advanced stage. C6S levels showed a
      markedly decreasing trend with advancing OA stage. C0S was not detected in
      synovial fluid. The present study demonstrated that serum levels of C4S and C0S
      in OA patients are elevated compared with normal subjects, and that synovial
      fluid levels of C4S and C6S may provide useful in assessing the pathology of OA.

PMID- 11301363
TI  - [Blood vessels in normal and abnormal mitral valve leaflets].
AB  - The incidence and the distribution of blood vessels were examined in normal and
      abnormal mitral valve leaflets. MATERIALS AND METHODS: Normal valves were
      obtained from 12 autopsy cases without cardiovascular disease (8 men, 4 women, 33
      to 93 years of age). Twenty-one abnormal valves were obtained at the time of
      mitral valve replacement (12 men, 9 women, 16 to 78 years of age). Clinical and
      pathological diagnoses were rheumatic valvular disease (RVD: n=8), floppy mitral
      valve (FMV: n=9), and healed infective endocarditis (HIE: n=4, 1 with RVD, 3 with
      FMV). The number of vessels was counted at the surgical excision line of the
      valvular rings by immunohistochemical study using Factor VIII related antigen and
      CD34. Histologic studies were also made at the 5 mm distal line from the ring in
      normal valves, and at the vertical line to the ring in abnormal valves. RESULTS:
      In normal valves, the number of vessels at the ring area, except in myocardial
      tissues that extended from the left atrium to the auricularis, ranged from 3 to
      184. Vessels were also found at the 5 mm distal area from the ring in 6 valves
      out of 12. Vessels were mainly distributed near the commissure areas of the
      auricularis and/or the spongiosa and were extended with myocardial tissues. There
      was no difference in the number of vessels related to age or sex. In RVD, the
      number of vessels at the ring area ranged from 22 to 517 in 8 anterior leaflets
      (AML) and 2 to 151 in 5 posterior leaflets (PML). Many vessels also appeared in
      the distal spongiosa of the leaflets, and arterioles were frequently found in
      these areas. In FMV, a few (3 and 6) vessels were found in 2 leaflets (AML: 2/8,
      PML: 0/4). In HIE, the number of vessels was 216 in the case with RVD, and 3 to
      110 in cases with FMV. CONCLUSION: At the ring area, normal mitral valve leaflets
      were supplied with nutrition from blood vessels that mainly extended from the
      left atrium with myocardial tissues. In RVD, the vessels branched from previously
      existing capillaries, extending to the distal area, and increased in number.
      Mechanical stress during opening and closing of the leaflets contributes to the
      arterialization of these vessels. In FMV, the number of capillaries, which is
      smaller than in normal valves, might be related to the progression of this
      disorder. In HIE with valvular disease, the number of vessels is related to the
      preexisting disease.

PMID- 11301364
TI  - The short-term effects of terazosin in Japanese men with benign prostatic
      hyperplasia.
AB  - We evaluated the short-term efficacy of terazosin for treating symptomatic benign
      prostatic hyperplasia (BPH). Thirty men, aged 52 to 83 years (mean: 69.2 years)
      complaining of obstructive urinary symptoms due to BPH who had not received any
      prior treatment for their symptoms were orally administered 2 mg/day of
      terazosin. Symptoms (the total IPSS and the obstructive and irritative symptom
      scores) and objective parameters (peak flow rate [Qmax] and prostatic volume)
      were evaluated before treatment and after 1, 2, and 4 weeks of treatment. The
      mean total IPSS and the mean symptom scores for weak stream and nocturia were
      significantly decreased after only 1 week of treatment, while the mean scores for
      emptying, frequency, and urgency were significantly decreased after 2 weeks of
      treatment. However, the mean scores for intermittency and hesitancy did not
      decrease significantly at any time during treatment. Regarding objective
      parameters, the mean Qmax was significantly improved after 1 week of treatment,
      but the mean prostatic volume remained almost unchanged after 4 weeks. In
      conclusion, short-term terazosin therapy not only improved Qmax but also
      alleviated symptoms including irritative symptoms.

PMID- 11301365
TI  - A case report of spondyloepiphyseal dysplasia congenita.
AB  - Spondyloepiphyseal dysplasia congenita (SED) is a rare form of skeletal systemic
      disease, characterized by congenital dwarfism with a short trunk and epiphysial
      dysplasia in the long bones and vertebral bodies. Patients also frequently suffer
      from atlanto-axial instability due to os odontoideum. Compression of the spinal
      cord caused by atlanto-axial instability is a common, serious complication in SED
      patients, and causes severe spinal cord symptoms or occasionally sudden death. We
      present an SED patient who underwent a posterior fusion of the occiput to the
      cervical spine for severe spinal cord symptoms due to atlanto-axial instability.

PMID- 11301366
TI  - [Lifestyle related diseases in children and adolescents].

PMID- 11301367
TI  - [Hyperlipidemia in life style disease].

PMID- 11301368
TI  - [A case of normal sized ovarian carcinoma with positive endometrial smear].

PMID- 11301369
TI  - New adjuvant strategies for breast cancer: meeting the challenge of integrating
      chemotherapy and trastuzumab (Herceptin).
AB  - Improvements in breast cancer treatment will arrive with better understanding of
      its biology and through biologically oriented therapeutic interventions as well
      as better identification of patient populations susceptible to benefit from
      classical therapies (endocrine and chemotherapy). Among the new chemotherapies,
      the taxanes have emerged as powerful agents in the treatment of metastatic breast
      cancer and a strong emphasis has been pursued into their development in the
      adjuvant setting. Two generations of adjuvant pivotal trials with taxanes have
      been developed. The first generation compared taxane/anthracycline regimens to
      nontaxane combinations or sequence regimens. The second generation of trials is
      presently being performed and contains taxanes in both arms, comparing their use
      in combination or in sequence. Trastuzumab (Herceptin; Genentech, Inc, South San
      Francisco, CA) is the first biologic modifier with significant activity in
      advanced breast cancer patients amplifying the HER2 gene. As a consequence of
      these results, including improved survival in the metastatic setting, this agent
      has been very quickly considered for adjuvant development. However, the
      significant cardiac toxicity observed with trastuzumab/anthracycline combinations
      has led to two main strategies for integrating trastuzumab in the adjuvant
      setting: (1) addition of trastuzumab to mostly anthracycline-based programs
      (sequential approach); and (2) biology-oriented strategy based on synergism
      between trastuzumab and chemotherapy agents. Large-scale clinical research
      programs are presently being developed and will create a challenge for clinical
      researchers. The adequate scientific hypothesis, related to the pivotal studies
      of trastuzumab in the adjuvant setting, require large sample sizes (several
      thousand patients) and a very strict selection of the patient population (tumors
      amplifying the HER2 gene). Success in a timely fashion requires global
      collaboration, dedication to high-standard clinical research, and awareness of
      all available protocols by oncologists and patients with breast cancer.

PMID- 11301370
TI  - Rationale for trastuzumab (Herceptin) in adjuvant breast cancer trials.
AB  - The discovery of the HER2/neu proto-oncogene and its role in the pathogenesis of
      breast cancer tumors, and the development of the anti-HER2 monoclonal antibody,
      trastuzumab (Herceptin; Genentech, South San Francisco, CA), directed against the
      HER2 receptor represent major milestones in the research developments in breast
      cancer, making trastuzumab the first monoclonal antibody available for treatment
      of this disease. Clinical trials in HER2-positive patients have demonstrated that
      the combined use of targeted therapy with trastuzumab in conjunction with
      cytotoxic chemotherapy is associated with improved time to disease progression
      and overall survival. Unfortunately, findings also demonstrate an increased risk
      for cardiotoxicity when trastuzumab is combined with anthracyclines. For HER2/neu
      overexpressing breast cancer patients, the adjuvant use of trastuzumab will
      become paramount; therefore, it must be evaluated in a randomized controlled
      trial. There is disagreement regarding the design of such a trial, largely
      because of the ubiquitous use of anthracyclines in the adjuvant setting and the
      opposing necessity of avoiding anthracycline plus trastuzumab combinations.
      Combination index values for various chemotherapeutic drugs in combination with
      trastuzumab demonstrate dramatic synergistic interactions with the platinum
      agents and with docetaxel (Taxotere; Aventis Pharmaceuticals, Inc, Parsippany,
      NJ). The greatest level of synergy has been demonstrated with the triple-drug
      combination of docetaxel, platinum, and trastuzumab in which synergy is
      demonstrated, even at low doses. The adjuvant trial design for the Breast Cancer
      International Research Group uses a control arm of doxorubicin/cyclophosphamide
      for four cycles followed by docetaxel for four cycles and the second arm contains
      the addition of trastuzumab to the taxane sequence. The third arm, a non
      anthracycline-containing regimen, contains docetaxel, a platinum agent (either
      cisplatin or carboplatin), and trastuzumab. The rationale for the selection of
      this three-drug regimen is based on the biology of the system and preclinical and
      clinical findings that demonstrate a high potential for clinical synergy.

PMID- 11301371
TI  - Cardiac toxicity of trastuzumab (Herceptin): implications for the design of
      adjuvant trials.
AB  - Trastuzumab (Herceptin; Genentech, South San Francisco, CA) is a humanized
      version of the murine monoclonal antibody 4D5 that was recently approved for the
      treatment of advanced breast cancer that overexpresses the HER2/neu oncogene.
      Cardiac toxicity was an unexpected side effect of trastuzumab treatment in the
      pivotal trials that led to its approval. The incidence of cardiac dysfunction was
      highly dependent on prior or concurrent doxorubicin exposure. For patients with
      minimal prior anthracycline exposure, the risk of cardiac dysfunction was 1%. For
      patients with more extensive prior doxorubicin exposure, the risk of cardiac
      dysfunction was 7% for trastuzumab monotherapy and 12% for trastuzumab plus
      paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ). For patients
      treated with trastuzumab concurrently with doxorubicin, the risk of cardiac
      dysfunction was 29%. The etiology of trastuzumab-associated cardiac dysfunction
      is unknown, although its dependence on concurrent or prior doxorubicin exposure
      suggests a common pathophysiologic basis with anthracycline-induced myocardial
      injury. A number of trials are in progress to evaluate the efficacy and safety of
      trastuzumab in patients with early stage disease and that will investigate novel
      strategies to circumvent this serious toxicity.

PMID- 11301372
TI  - The platinum agents: a role in breast cancer treatment?
AB  - Metastatic breast cancer is a partially chemotherapy-sensitive neoplasm. Most
      chemotherapy groups have activity in this disease, and the most active single
      drugs are the taxanes, especially docetaxel (Taxotere; Aventis Pharmaceuticals,
      Inc, Parsippany, NJ), and the anthracyclines. The alkylating agents,
      antimetabolites, and vinca alkaloids are also widely used. The platinum
      coordination complexes, which are widely used in oncology, are also active in
      metastatic breast cancer, but the availability of other drugs that are less toxic
      and easier to administer has resulted in their having a strictly limited use in
      this setting. Cisplatin appears to be somewhat more active than carboplatin, but
      direct comparative studies are lacking. The identification of the prominent
      activity of the taxanes has led to the investigation of wholly novel non
      anthracycline-containing combination regimens, and platinum/taxane doublets
      appear to be particularly active. More recently, reports that trastuzumab
      (Herceptin, Genentech, South San Francisco, CA), a novel monoclonal antibody
      directed against the protein product of the HER2/(neu) oncogene, has a powerful
      synergistic interaction with docetaxel and with platinum agents have prompted
      evaluation of the triplet docetaxel/platinum/trastuzumab in the therapy of
      metastatic breast cancer.

PMID- 11301373
TI  - Docetaxel (Taxotere) plus trastuzumab (Herceptin) in breast cancer.
AB  - The rationale for the combined use of docetaxel (Taxotere; Aventis
      Pharmaceuticals, Inc, Parsippany, NJ) and trastuzumab (Herceptin; Genentech,
      South San Francisco, CA) in HER2/neu-overexpressing breast cancer patients are
      several-fold. Docetaxel is a highly active chemotherapeutic agent in metastatic
      breast cancer. Response rates, time to progression, and survival are improved
      when trastuzumab is combined with chemotherapy. Finally, preclinical findings
      demonstrate synergistic cytotoxic activity when docetaxel and trastuzumab are
      combined. In addition, their different mechanisms of action and a nonoverlapping
      toxicity profile suggest the potential for a highly useful combination while
      minimizing potential cardiotoxicity. An ongoing pilot phase II evaluation is
      being conducted with every-3-week docetaxel plus weekly trastuzumab. Preliminary
      findings suggest an active and well-tolerated regimen. Efficacy data indicate an
      encouraging overall major response rate of 45% in first- and second-line
      metastatic breast cancer patients. Preliminary results from a second phase II
      trial of weekly docetaxel and trastuzumab have been reported. In 14 patients
      treated to date, grade (3/4) toxicities are infrequent. An overall response rate
      of 54% is reported thus far with 26 cycles (156 weeks) of therapy delivered. The
      preliminary data for the docetaxel and trastuzumab combinations look favorable
      from both a safety and an efficacy perspective. The lack of cardiac function
      changes despite frequent cardiac monitoring is promising. For the adjuvant
      therapy of HER2/neu-overexpressing breast cancer, the high level of efficacy of
      docetaxel and the need to identify nonanthracycline agents for combined use with
      trastuzumab place a high emphasis on the potential utility of docetaxel and
      trastuzumab-based regimens.

PMID- 11301375
TI  - Will our planet be able to cope with the cancer burden in the next decade?

PMID- 11301376
TI  - Lung cancer in Brazil.
AB  - Lung cancer is the second leading cause of death in Brazil, after exclusion of
      external causes. Registries in the country are not reliable because of under
      registration and limited coverage. Incidence rates for Brazil are less then half
      those for selected areas with good registries. Crude and adjusted incidence and
      mortality rates for lung cancer are rising, particularly among women. The main
      reason is the acceleration in tobacco consumption and the spread of smoking among
      women. At present, approximately 40% of men and 25% of women, 15 years of age or
      older, are current smokers. In the state of Rio Grande do Sul, where registries
      are reliable, incidence and mortality for males are similar to US data and the
      figures for women are rapidly approaching those for men. Occupations associated
      with risks of exposure to respiratory carcinogens show a rise in the incidence of
      lung cancer in the industrialized area of Sao Paulo. The main occupational risk
      in Brazil is exposure to mineral dusts, silica, or asbestos. Although about 15
      million Brazilians are exposed to pesticides, agricultural workers were not a
      risk group for lung cancer in a case-control study. Pesticides containing arsenic
      and dichlorodiphenyltrichloroethane (DDT) are banned. In recent years, a trend
      towards a decrease in male smoking has been noted, but there is still a high
      tobacco exposure burden in both males and females, with a forecast of a further
      increase in rates of lung cancer incidence and deaths. Control of respiratory
      carcinogens at work continues to be a problem, particularly in the present
      scenario of economic and political pressures on Brazil and other developing
      nations. Semin Oncol 28:143-152.

PMID- 11301377
TI  - Esophageal cancer in Iran.
AB  - Esophageal cancer is among the 10 most frequent cancers in the world. Iran is one
      of the known areas with a high incidence of esophageal cancer. Most of the
      patients in Iran have been reported from the north and northeast regions of the
      country. In one survey by the Iran Cancer Institute, 9% of all cancers and 27% of
      gastrointestinal cancers were esophageal carcinoma. The male to female ratio was
      1.7/1. The distal portion of the esophagus is involved more often than other
      parts. Consumption of wheat flour, exposure to residues from opium pipes,
      drinking hot tea, and chewing nass (a mixture of tobacco, lime, ash, and other
      ingredients) are the suspect etiologic agents for esophageal cancer in Iran.
      Dysphagia, weight loss, anorexia, abdominal pain, and odynophagia are the common
      symptoms and signs of Iranian patients with esophageal cancer. For clinical
      staging, chest computed tomographic scanning is performed. Adenocarcinoma of the
      esophagus is not as common in Iran as in western countries. Public education,
      nutritional support, and eradication of opium addiction may decrease the
      morbidity and mortality that result from esophageal cancer. Surgery has
      traditionally been the mainstay of esophageal cancer treatment in Iran.
      Radiotherapy is mainly used postoperatively. The usual combination chemotherapy
      regimen is cisplatin plus flurouracil (5-Fu). Semin Oncol 28:153-157.

PMID- 11301378
TI  - The burden of mouth cancer in Latin America and the Caribbean: epidemiologic
      issues.
AB  - The incidence rates of mouth cancer vary from low to high among the countries of
      Latin America and the Caribbean. This review will examine incidence and mortality
      rates according to risk factors for the disease. Studies of local populations are
      reviewed and common patterns established. Although the incidence rate of mouth
      cancer is decreasing in some countries, a large increase is observed in southern
      South America. This trend will probably be maintained over the next few decades.
      Specific risk factors have been identified: high tobacco smoking and alcohol
      drinking prevalence, high intake of charcoal-grilled red meat, and mate drinking.
      The increase in tobacco smoking among females will have a strong impact on the
      incidence of mouth cancer in the future. In some Latin American and Caribbean
      countries, lay educational information on cancer is scant. The importance of
      improving information systems on cancer and the development of tobacco smoking
      and alcohol control programs are stressed. The training of health practitioners
      in the early detection and treatment of mouth lesions is a public health goal
      that could improve survival, but the difficulties encountered by people from the
      lowest socioeconomic strata in obtaining access to primary health care could
      hinder this objective. Semin Oncol 28:158-168.

PMID- 11301379
TI  - Oral cancers in India.
AB  - Oral cancers in India constitute a major portion of all cancers. With a
      population of 1,000 million, this cancer poses many challenges. More than 90% of
      cases are tobacco-related, and hence eminently amenable to primary prevention.
      The progress made in these cancers is helping us to address the problem in a
      better way, bringing hope to overcome the misery. Semin Oncol 28:169-173.

PMID- 11301380
TI  - Bladder cancer in Africa: update.
AB  - Carcinoma of the bladder is the most prevalent cancer in Egypt and in most
      African countries. At the National Cancer Institute (NCI), Cairo, it constitutes
      30.3% of all cancers. The median age at diagnosis is 46 years, with a male
      preponderance of 5:1. Whether in Egypt or other African countries such as Sudan,
      Kenya, Uganda, Gold Coast, and Senegal, it is mostly of the squamous cell type,
      and arises in a background of schistosomiasis or bilharziasis. Tumors are usually
      advanced at the time of presentation. Bladder carcinogenesis is probably related
      to bacterial and human papilloma virus (HPV) infections, usually associated with
      bilharzial infestation. Management is mainly surgery, with 5-year survival rates
      after radical cystectomy increasing from 35% in the 1970s to 48% in the 1990s.
      The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to surgery
      since 1976 significantly improved both disease-free and overall survival rates.
      Molecular genetic studies concerning potential prognostic markers, tumorigenesis,
      and tumor progression in bilharzial bladder cancer are limited. However, a
      comprehensive detailed analysis of these factors is underway. Bilharzial bladder
      cancer is a preventable malignant disease. Primary prevention could be possible
      if the parasite is eliminated nationwide. Chemoprevention using retinoids or
      cyclooxygenase 2 (COX-2) inhibitors is a possible alternative. Semin Oncol 28:174
      178.

PMID- 11301381
TI  - Hepatocellular carcinoma in the developing world.
AB  - There has recently been an observable increase in some forms of cancer the world
      over. This is attributable in large part to the introduction of acquired
      immunodeficiency syndrome (AIDS)-related malignancies into the world of medicine
      and it is interesting that most of these cases are seen in the developing world,
      which proportionately leads with the number of AIDS cases. Despite this, some
      more traditional cancers remain the big killers in these areas of the world,
      except that in some countries definitive interventions have yielded excellent
      results in reducing disease burden. In Africa and the developing world,
      hepatocellular carcinoma (HCC) is the leading cause of cancer death, having some
      clearly established etiologic factors. This review describes the current status
      of each of these known etiologic factors in the various areas and, using
      available evidence, suggests options that may be employed to further stem the
      incidence of HCC and improve on survival in these populations. Semin Oncol 28:179
      187.

PMID- 11301382
TI  - Cervical cancer in Latin America.
AB  - Cervical cancer is a common cause of morbidity and mortality in developing
      countries. In Latin America, the incidence rates in several cities are among the
      highest worldwide, probably due to a high frequency of risk factors and/or a low
      screening coverage for cervical cancer. Epidemiologic studies conducted in Latin
      America (and some in the Caribbean), that have investigated the main risk factors
      for the disease, as well as screening coverage by Papanicolaou (Pap) smear, were
      reviewed. The prevalence of human papillomavirus (HPV) infection among women with
      negative Pap smears does not seem to explain the risk observed in Latin American
      countries. Results of some studies have suggested that reproductive factors and
      male sexual behavior might be responsible, at least partially, for the high
      occurrence of cervical cancer in Latin America. Concerning cytology screening,
      many women have a smear taken regularly (some every year). However, a significant
      proportion of women, probably those with a high risk of cancer of the cervix,
      have never had a Pap test. To reduce cervical cancer in these countries,
      screening programs in Latin America should have a wider coverage, especially
      reaching those women at higher risk. Semin Oncol 28:188-197.

PMID- 11301383
TI  - Acquired immunodeficiency syndrome-associated cancers in Sub-Saharan Africa.
AB  - Sub-Saharan Africa is considered home to more than 60% of all human
      immunodeficiency virus (HIV) infected cases, with an estimated adult prevalence
      of 8.0%. It is stated that this region has contributed more than 90% of childhood
      deaths related to HIV infection and about 93% of childhood acquired
      immunodeficiency syndrome (AIDS)-related deaths. Although no country in Africa is
      spared of the infection, the bulk is seen in East and South Africa, with the
      highest recorded rates of 20% to 50% in Zimbabwe. On the other hand, West Africa
      is less affected, while countries in Central Africa have relatively stable
      infection rates. Although infections, especially tuberculosis, have emerged as
      the most important HIV/AIDS-associated killers in recent times, AIDS-associated
      malignancies are increasingly identified in the late stages. As a result of
      incomplete data from African countries, it is unclear whether the epidemiology
      and risks of these cancers are the same as observed in the developed countries.
      Since the advent of AIDS, epidemic Kaposi's sarcoma (KS) has become more common
      in both sexes in Africa, with a dramatic lowering of the male to female ratio
      from 19:1 to 1.7:1, especially in East Africa. Although there has been a rising
      trend of AIDS-associated non-Hodgkin's lymphoma (NHL) worldwide, there is an
      apparently lower risk in Africa compared with that in the developing world. At
      present, there is no strong evidence linking increased incidence of invasive
      cervical cancer to the HIV epidemic; however, some studies have demonstrated an
      association between HIV and the increased prevalence of human papilloma virus
      (HPV) and cervical intraepithelial neoplasia (CIN). On the other hand, HIV
      infection is now established as a risk factor for the development of squamous
      cell neoplasia of the conjunctiva based on studies from Rwanda, Malawi, and
      Uganda. Despite the problems and limitations of information from sub-Saharan
      Africa, interesting trends of HIV/AIDS-related cancers have emerged from
      comparison of available data. Semin Oncol 28:198-206.

PMID- 11301384
TI  - Inequalities in cancer risks.
AB  - Inequalities in health reflect social inequalities in society. The incapacity of
      our society to eliminate poverty is indeed one of the most blatant examples of
      failure in prevention. Every individual's health history is characterized by life
      long influences and superimposed short-term factors, but health biographies of
      the rich and the poor show divergences that are the result of the accumulation
      and interaction of a series of events that may be quantitatively and
      qualitatively different. Schematically this could, for example, mean that certain
      individuals, or certain segments of the populations, are exposed more frequently
      and to more hazardous agents than others and/or less frequently to protective
      agents. Sanitary conditions are worse, mortality higher, survival rates of cancer
      patients lower, and life expectancy shorter in developing countries than in
      industrialized countries. The projection of the total number of cancer cases in
      the next decades indicates a general increase, proportionally greater in
      developing than in industrialized countries. Semin Oncol 28:207-209.

PMID- 11301385
TI  - Cancer: a reality in the emerging world.
AB  - World societies have changed significantly in the last decades. The main
      characteristics of these changes are reciprocal connections and
      interdependencies. It has been thus realized that a major part of the world
      population still lives in poverty. Due to specific health care interventions and
      consequent demographic changes, it is expected that the population in general,
      and of the older people in particular, will increase significantly in the future.
      The annual number of new cases of cancer is expected to double from 10 million at
      present to 20 million in the next 20 years. Considering the increases in life
      expectancy and in tobacco abuse worldwide, and the existence of viral diseases
      leading to cancer in less developed countries besides other factors, the majority
      of new cases will probably occur in the emerging world. The number of new cases
      of cancer could in the future be reduced with the enhancement of education on
      vertical and horizontal levels in less developed countries. On the vertical arm,
      the education would concentrate on physicians, nurses, and other health care
      workers, while on the horizontal arm, it would be provided to government
      officials, politicians, and other decision-makers. It should be accepted that the
      world is one and that the problems associated with cancer in less developed
      countries are global problems. Semin Oncol 28:210-216.

PMID- 11301386
TI  - Detection of Kaposi sarcoma-associated herpesvirus in bone marrow biopsy samples
      from patients with multiple myeloma.
AB  - BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) recently has been
      identified in the bone marrow (BM) dendritic cell of multiple myeloma (MM)
      patients. However, whether or not KSHV is associated with MM remains
      controversial because many studies have failed to detect the presence of KSHV DNA
      sequences in the BM of their MM patients. METHODS: We have assayed for KSHV DNA
      sequences in the BM biopsy samples from 49 patients with MM and from 8 patients
      with normal BM, using nested polymerase chain reaction and dot blot analysis. The
      polymerase chain reaction product of KSHV was further determined by single-strand
      conformation polymorphism and sequence analyses. RESULTS: KSHV DNA was detectable
      in 22 of 49 patients (44.9%) with MM but was not detectable in normal BM cells.
      Single-strand conformation polymorphism and sequence analyses showed that there
      were interpatient specific mutations. Sixteen out of 22 KSHV DNA sequences
      belonged to a previously defined subgroup, and the other 6 remain unclassified
      and may represent distinct strains of KSHV in Taiwan. CONCLUSIONS: Data strongly
      supported that KSHV infection did exist in the BM of the current study patients
      with MM. However, the role of KSHV in the pathogenesis of multiple myeloma
      remains to be determined.

PMID- 11301387
TI  - Analysis of clinicopathologic factors predicting outcome after radical
      prostatectomy.
AB  - BACKGROUND: A variable biochemical failure rate has been reported for patients
      undergoing radical prostatectomy. The authors analyzed their 1987-1993
      prostatectomy experience retrospectively to stratify the risk of failure in order
      to appropriately select patients who potentially may benefit from adjuvant
      therapy. METHODS: A stepwise logistic regression was used to identify variables
      associated with biochemical failure in 265 patients who underwent radical
      prostatectomy only. Prostate tumors were examined by one pathologist using 4-mm
      step sections. Numerous clinicopathologic variables were evaluated, and the
      neoplasms were subclassified into five pathologic categories based on tumor
      extent and margin status. Actuarial projections of biochemical failure were
      created using the Kaplan-Meier method. RESULTS: Pathologically, 56.2% of the
      tumors were organ-confined with negative margins, 12.8% had a positive surgical
      margin without evidence of extraprostatic extension (EPE), 24.2% had EPE (17%
      with negative margins and 7.2% with positive margins), and 6.8% had seminal
      vesicle involvement. The Gleason score was > or = 7 in 86.4% of the total
      population. Values for the preoperative prostate specific antigen assay were < or
      = 4.0 ng/mL in 23.4% of the men and > 10 ng/mL in 27.7%. The overall observed
      biochemical failure rate in this patient group with a minimum 48 months of follow
      up was 15.5%. Overall, stepwise logistic regression analysis revealed that
      pathologic category was the variable most strongly associated with biochemical
      failure and that vascular invasion was the only other examined variable
      associated with failure. CONCLUSIONS: The combination of pathologic category and
      the prostatectomy Gleason score can stratify a patient's probability of
      biochemical failure into three distinct groups and can identify the appropriate
      patients who may benefit from novel adjuvant therapeutic strategies.

PMID- 11301388
TI  - Anti-Ri-associated paraneoplastic opsoclonus-ataxia syndrome in a man with
      transitional cell carcinoma.
AB  - BACKGROUND: There are several case reports describing paraneoplastic syndromes in
      patients with various forms of bladder carcinoma. Current immunologic analyses
      have enabled the identification of the antineuronal autoantibodies associated
      with specific syndromes. METHODS: A patient with a history of bladder carcinoma
      presented with opsoclonus and myoclonus. RESULTS: Workup confirmed the presence
      of anti-Ri antibodies in the patient's serum and cerebrospinal fluid. The target
      Ri antigen was found to be expressed by the tumor. CONCLUSIONS: To the authors'
      knowledge, there are few reports in the literature describing the long-term
      clinical follow-up and postmortem evaluation in a patient with this form of
      paraneoplastic syndrome. More important, the authors believe the current study
      represents the first time that the presence of anti-Ri antibodies has been noted
      in a paraneoplastic syndrome associated with transitional cell carcinoma of the
      bladder.

PMID- 11301389
TI  - Regulation of vascular endothelial growth factor transcription by endothelial PAS
      domain protein 1 (EPAS1) and possible involvement of EPAS1 in the angiogenesis of
      renal cell carcinoma.
AB  - BACKGROUND: Endothelial PAS domain protein 1 (EPAS1) is a basic helix-loop
      helix/PAS domain transcription factor that expressed most abundantly in highly
      vascularized organs. The authors examined the effect of transfection of EPAS1
      cDNA on the endogenous expression of vascular endothelial growth factor (VEGF) in
      the 293 Tet-Off cell line and the possible involvement of EPAS1 in the
      angiogenesis of renal cell carcinoma (RCC). METHODS: Complete cDNA of EPAS1 was
      cloned and transfected to cells from the 293 Tet-Off fetal kidney cell line, in
      which the expression of EPAS1 can be inhibited by doxycycline. The subsequent
      changes in expression pattern of VEGF and transferrin receptor (TfR), a target
      gene of hypoxia-inducible factor 1alpha (HIF-1alpha), were examined by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and
      enzyme-linked immunosorbent assay. In addition, expression of EPAS1, HIF-1alpha,
      and VEGF were analyzed by semiquantitative RT-PCR in five RCC cell lines and in
      13 RCC tissue samples. In situ hybridization was performed on 7 of the 13 RCC
      tissue samples. RESULTS: Endogenous VEGF was increased significantly by the
      introduction of EPAS1 cDNA at both the mRNA level and the protein level. With the
      inhibition of EPAS1 by doxycycline treatment, the expression of VEGF was
      significantly decreased accordingly, whereas the expression of TfR was not
      affected. EPAS1 was detected in all of the RCC cell lines examined. In RCC tissue
      samples, EPAS1 mRNA and VEGF mRNA were increased significantly in tumor tissues
      compared with normal adjacent kidney tissues. In situ hybridization showed that
      EPAS1 and VEGF were coexpressed topographically in tumor tissues. CONCLUSIONS:
      These results suggest that endogenous VEGF can be up-regulated transcriptionally
      by EPAS1, and EPAS1 may be involved in the angiogenesis of RCC.

PMID- 11301390
TI  - Multimodality therapy for patients with clinical Stage I and II malignant mixed
      Mullerian tumors of the uterus.
AB  - BACKGROUND: The role of adjuvant therapy in the management of patients with
      malignant mixed Mullerian tumors (MMMT) of the uterus has not been defined. The
      outcome of planned multimodality therapy for patients with apparent early stage
      disease was assessed. METHODS: A pilot study was performed on 38 patients with
      clinical Stage I or II MMMTs of the uterus who were offered treatment according
      to a standard protocol. The protocol consisted of removal of the uterus,
      fallopian tubes, and ovaries and surgical staging followed by tailored radiation
      therapy and chemotherapy, consisting of cisplatin and epirubicin. RESULTS: The
      overall survival was 74% (28 of 38 patients), with a mean duration of follow-up
      for survivors of 55 months (range, 17-121 months). The mean time to death from
      disease was 26 months (range, 7-87 months). The survival rate for those patients
      who completed treatment according to the multimodality protocol was 95% (20 of 21
      patients), with a disease free survival rate of 90% (19 of 21 patients). The
      overall survival of patients who did not receive the recommended treatment
      protocol for various reasons was 47% (8 of 17 patients). An analysis of survival
      curves demonstrated that there was a significant survival advantage for those
      patients who completed the treatment according to the multimodality protocol (P =
      0.01). CONCLUSIONS: In this pilot study, patients with clinical Stage I or II
      MMMTs who underwent surgical staging and aggressive adjuvant radiation and
      chemotherapy had an excellent survival rate. The results justify a randomized
      prospective study of this approach.

PMID- 11301391
TI  - Duration of symptoms prior to diagnosis is related inversely to presenting
      disease stage in children with medulloblastoma.
AB  - BACKGROUND: The authors tested the hypothesis that children with a longer
      duration of symptoms prior to diagnosis of medulloblastoma have more advanced
      disease. In addition, they evaluated whether there are correlations between
      gender, duration of presenting symptoms, and disease stage. METHODS: The study
      population consisted of 122 patients with medulloblastoma who were evaluated
      between 1974 and 1999. The data abstracted from each chart included the date of
      diagnosis, date of birth, gender, race, presenting symptoms, duration of symptoms
      in weeks, and disease stage. RESULTS: There were 70 males (57%) and 52 females
      (43%); 105 Caucasians (86%), 16 non-Caucasians (13%), and 1 patient of unknown
      race. Eighteen percent of the patients were age < or = 3 years, 59% were ages 4
      16 years, and 23% were age > or = 17 years. The presenting stage was determined
      in 108 patients. Thirty-eight patients (35%) had high stage disease (T1-T4 M1
      M4), and 70 patients (65%) had low stage disease (T1-T4 M0). The most common
      presenting symptoms were emesis (68%), headache (66%), nausea (40%), and ataxia
      (40%). The median symptom durations for patients ages 0-3 years were 4 weeks and
      8 weeks for both those ages 4-16 years and those age > or = 17 years,
      respectively (P > 0.11). The median symptom duration for males (8 weeks) was
      longer than for females (5 weeks; P = 0.08). Patients with low stage disease had
      a median duration of symptoms (8 weeks) that was significantly greater compared
      with patients with high stage disease (4 weeks; P = 0.01). Relating patient age
      to disease stage, 47% of patients ages 0-3 years had high stage disease; 36% of
      patients ages 4-16 years had high stage disease; and 24% of patients age > or =
      17 years had high stage disease (P = 0.20). Relating disease stage to gender, 40%
      of males had high stage disease compared with 28% of females (P = 0.20). Of the
      factors age, gender, race, and duration of symptoms, only the later was
      correlated significantly with disease stage at the time of presentation in both
      univariate and multivariate analyses. CONCLUSIONS: Contrary to expectations, the
      duration of presenting symptoms was correlated inversely with disease state at
      the time of presentation. This finding has implications for lawsuits alleging
      that a "delay in diagnosis" leads to more advanced disease. There is weak
      evidence (P = 0.08) that males have a longer duration of symptoms than females.
      This may be related to gender-associated behavior expectations.

PMID- 11301392
TI  - Microsatellite instability and hMLH1/hMSH2 expression in Barrett esophagus
      associated adenocarcinoma.
AB  - BACKGROUND: Microsatellite instability (MSI) has been documented in malignancies
      associated with hereditary nonpolyposis colon carcinoma and in sporadic
      malignancies of the colon, stomach, and endometrium. In these malignancies, MSI
      is associated with defects in the DNA mismatch repair enzymes hMSH2 and hMLH1.
      Defects in these enzymes result in a phenotype characterized by instability of
      multiple microsatellite repeat sequences throughout the genome. This study sought
      to determine the prevalence of MSI in 80 primary Barrett esophagus-associated
      adenocarcinomas (BEAd) and to examine the relation of MSI with the clinical and
      pathologic features of the tumors. METHODS: Eighty BEAd were evaluated for the
      presence of MSI by using the microsatellite markers BAT25, BAT26, D10S219,
      D10S541, and D10S551. These tumors also were evaluated for immunohistochemical
      expression of hMSH2 and hMLH1. RESULTS: High levels of MSI were not found in any
      of the tumors examined. Furthermore, immunohistochemical expression of hMSH2 and
      hMLH1 was retained in all cases evaluated. Evidence of low level MSI was found in
      16% of tumors. In none of these tumors, however, was MSI present in more than two
      of five loci. The presence of MSI did not correlate with patient age, tumor
      stage, degree of differentiation, or with patient survival. CONCLUSIONS: High
      level MSI and loss of hMLH1/hMSH2 expression is uncommon in BEAd. A subset of
      BEAd demonstrate low level MSI. The presence of low level MSI was not associated
      with the clinicopathologic features of the tumors examined.

PMID- 11301393
TI  - Aspects of intracranial and spinal tumors in patients with Down syndrome and
      report of a rapidly progressing Grade 2 astrocytoma.
AB  - BACKGROUND: Brain tumors in patients with Down syndrome (DS) rarely are reported,
      and their behavior is not well known. METHODS: The authors report on a male
      patient age 19 years who had DS with diffuse astrocytoma (World Health
      Organization Grade 2) that recurred twice despite treatment, leading to a
      glioblastoma and, finally, to death in just over 2 years. The literature on brain
      tumors in patients with DS is reviewed. RESULTS: Although brain neoplasms were
      suspected to be in excess in patients with DS, the authors found only 36 patients
      with brain neoplasms and 2 spinal tumors. An unusual distribution of histologic
      tumor types, with an over-representation of germ cell and mesenchymal tumors and
      a lack of embryonal tumors, was observed, in agreement with what is known
      currently about the tumor profile of patients with DS. CONCLUSIONS: Cerebral
      tumors in patients with DS have a specific distribution and may behave
      differently compared with the general population. These features may be related
      to the gene dosage effect of oncogenes, antioncogenes, and genes involved in
      cerebral development due to the supernumerary chromosome 21.

PMID- 11301394
TI  - Comparison of prognostic models in patients with advanced Hodgkin disease.
      Promising results from integration of the best three systems.
AB  - BACKGROUND: Several prognostic systems have been elaborated for patients with
      Hodgkin disease (HD) over the last 12 years, but early identification of a
      reasonably large group of both low and high risk, advanced stage patients remains
      unsatisfactory. METHODS: Seven well known models were applied to 516 patients
      with advanced HD, with 315 patients used for the study sample and 201 patients
      used for the test sample. Individual performances as well as joint performances
      were analyzed univariately and multivariately in relation to overall survival,
      recurrence free survival, and time to treatment failure by means of a
      proportional hazards model. RESULTS: None of the models identified a group
      containing > 10% of patients from the total population who had a failure risk of
      either < or = 10% or > or = 50%. The systems of the International Database on
      Hodgkin Disease, the Memorial Sloan-Kettering Cancer Center, and the
      International Prognostic Factor Project showed the best prognostic power; only
      these three, when analyzed together, predicted clinical outcome with a
      statistically significant fit to the clinical data. Integration of the three
      systems in a linear model dramatically improved their individual discriminatory
      capacity by identifying patients with 10% and 50% failure risks, respectively, in
      23% and 24% of the study patient population and in 19% and 25% of the test
      population, respectively. CONCLUSIONS: As powerful and simple new prognostic
      factors are awaited that may improve our predictive ability, this integrated
      index is probably the best way to exploit the significance of those presently
      available. The program required for the calculations can be downloaded from the
      Internet at the web site http://www.unimo.it/gisl/default.htm.

PMID- 11301395
TI  - Experience of 1000 patients who underwent hepatectomy for small hepatocellular
      carcinoma.
AB  - BACKGROUND: Recently, the implementation of screening programs using alpha
      fetoprotein (AFP) and ultrasonography in high risk populations has identified
      increasing numbers of patients with small hepatocellular carcinoma (small HCC).
      The aim of this study was to summarize the authors' experience in patients who
      underwent hepatectomy for small HCC and the factors that influence or improve
      long term survival. METHODS: The study included 1000 patients who underwent
      hepatectomy for small HCC (< or = 5 cm) and compared them with 1366 patients who
      underwent hepatectomy for large HCC (> 5 cm) during the same period. A Cox
      proportional-hazards model was used for multivariate analysis of prognostic
      factors. RESULTS: Comparison between patients with small HCC (n = 1000 patients)
      and patients with large HCC (n = 1366 patients) revealed that those with small
      HCC had a higher resection rate (93.6% [1000 of 1068 patients] vs. 55.7% [1366 of
      2451 patients]; P < 0.01), a higher curative resection rate (80.5% [805 of 1000
      patients] vs. 60.7% [829 of 1366 patients]; P < 0.01), a lower operative
      mortality rate (1.5% [15 of 1000 patients] vs. 3.7% [50 of 1366 patients]; P <
      0.01), better differentiation of tumor cells (Edmondson Grade 3-4; 14.9% vs.
      20.1%; P < 0.01), a higher incidence of single nodule tumors (82.6% vs. 64.4%; P
      < 0.01), a higher proportion of well encapsulated tumors (73.3% vs. 46.3%; P <
      0.01), a lower incidence of tumor emboli in the portal vein (4.9% vs. 20.8%; P <
      0.01), and higher survival rates after undergoing resection (5 years: 62.7% vs.
      37.1%; P < 0.01; 10 years: 46.3% vs. 29.2%; P < 0.01). No significant difference
      was found between survival after undergoing minor resection (n = 949 patients) or
      lobectomy (n = 51 patients) in patients with small HCC (P > 0.05). Reresection
      for subclinical recurrence or solitary pulmonary metastasis after small HCC
      resection was undertaken in 84 patients. CONCLUSIONS: Resection is still the
      modality of first choice for the treatment of patients with small HCC. Minor
      resection instead of lobectomy was the key to increasing resectability and
      decreasing operative mortality, and reresection for subclinical recurrence or
      solitary pulmonary metastasis was important approach to prolonging survival
      further.

PMID- 11301396
TI  - Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases
      in patients with lung carcinoma.
AB  - BACKGROUND: Several biochemical markers of bone formation and bone resorption
      have been developed recently. The authors evaluated the usefulness of new
      biomarkers, such as urinary deoxypyridinoline (D-PYD), serum pyridinoline cross
      linked C-telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross
      linked N-telopeptides of Type I collagen (NTx), in the assessment of bone
      metastases in patients with lung carcinoma. METHODS: The serum concentrations of
      1CTP and the urinary concentrations of D-PYD and NTx were measured in 100 lung
      carcinoma patients, of whom 20 patients had bone metastases and 80 patients did
      not. Receiver operating characteristic (ROC) curves were drawn for these markers
      to compare their usefulness in detecting bone metastases originating in lung
      carcinoma. RESULTS: Urinary concentrations of NTx in patients with bone
      metastases were significantly greater than in patients without bone metastases
      (147.1 +/- 129.3 pmol bone collagen equivalents [BCE]/micromol Cr vs. 47.2 +/-
      29.9 pmol BCE/micromol Cr; P < 0.0001). Urinary concentrations of D-PYD in
      patients with bone metastases also were significantly greater than in patients
      without bone metastases (10.0 +/- 3.6 BCE/micromol Cr vs. 6.6 +/- 2.2 pmol
      BCE/micromol Cr; P = 0.0001). No significant difference was observed in serum
      concentrations of 1CTP between patients with and without bone metastases. A
      moderate but significant correlation was seen between NTx and D-PYD (correlation
      coefficient [R] = 0.435; P < 0.0001) and between D-PYD and 1CTP (R = 0.525; P <
      0.0001). NTx had a better ROC curve than D-PYD and 1CTP (the areas under the ROC
      curve were 0.84, 0.79, and 0.62, respectively). Using the threshold of 62.5 pmol
      BCE/micromol Cr for NTx, sensitivity, specificity, and accuracy were 0.800,
      0.737, and 0.750, respectively. CONCLUSIONS: In the current study, the
      measurement of NTx appeared to be most useful as a marker of bone metastases in
      patients with lung carcinoma.

PMID- 11301397
TI  - Oncoprotein 18 overexpression increases the sensitivity to vindesine in the human
      lung carcinoma cells.
AB  - BACKGROUND: Oncoprotein 18 (op18) was first isolated as a molecule overexpressed
      in several malignant cells, suggesting a function of op18 in malignant processes,
      such as differentiation in hematologic malignancies, op18 also was found to
      enhance microtubule deassembly in the cells. Antimitotic agents that bind to
      tubulin have been used for chemotherapy to treat solid tumors, such as lung
      carcinoma. Vinca alkaloids, such as vindesine and vincristine, have commonly been
      used for chemotherapy of nonsmall cell lung carcinoma. The authors examined the
      role of op18 in the sensitivity of human lung carcinoma cells to antimitotic
      agents. METHODS: Expression of op18 mRNA was detected in all 17 lung carcinoma
      cell lines tested by Northern blotting. Oncoprotein 18 cDNA was transfected to
      SBC-3 human lung carcinoma cells, and the stable transfectants, SBC-3/op1-3, were
      isolated. The sensitivity of these transfectants against antimitotic agents were
      examined by the MTT assay in vitro. Cell cycle distribution of the transfectants
      on DNA histogram was analyzed by flow cytometry. RESULTS: Oncoprotein 18
      transfected cells showed higher sensitivity to vindesine and vincristine, but not
      to taxanes. Vindesine-exposure increased the G2/M population of the cell cycle in
      the Mock transfectants, but not in SBC-3/op1, suggesting that the cell cycle
      dynamics were altered by op18 expression in SBC-3/op1. CONCLUSION: Oncoprotein 18
      expression is associated with lung carcinoma cell sensitivity to vindesine and
      may be able to serve as a surrogate marker for the chemosensitivity to Vinca
      alkaloids in human lung carcinomas.

PMID- 11301398
TI  - Patterns of angiogenesis in nonsmall-cell lung carcinoma.
AB  - BACKGROUND: Tumor angiogenesis plays a pivotal role in tumor growth, maintenance,
      and metastasis. The objective of the current study was to evaluate the prognostic
      value of estimates of tumor angiogenesis and vascular endothelial growth factor
      (VEGF) status in 143 primary tumors from patients who underwent radical surgery
      for nonsmall-cell lung carcinoma (NSCLC). METHODS: Tumor sections were stained by
      immunohistochemistry for CD34 and VEGF. Angiogenesis was estimated both by a
      modification of the method described by Weidner and by the use of a 25-point
      Chalkley eyepiece graticule. VEGF intensity was evaluated semiquantitatively in
      three groups of patients. The vascular data were correlated with histopathologic
      tumor type and grade, TNM classification, patient age, and the endpoint (death).
      RESULTS: The estimates of vascular score did not reveal any prognostic
      information. In 35 patients (24%), invasive tumor growth was identified with a
      highly ordered alveolar microvessel pattern. In parallel sections, the intensity
      of VEGF staining was weak in tumors that exhibited an alveolar microvessel
      pattern only, and it was more intense in tumors that demonstrated a mixed
      alveolar and diffuse angiogenic pattern. The 35 patients with alveolar
      microvessel pattern had a significantly better survival (P = 0.007). In a Cox
      multivariate analysis, the results demonstrated an independent bad prognostic
      value of high disease stage (P < 0.0001), adenocarcinoma (P = 0.004), greater age
      (P = 0.01), and angiogenic microvessel pattern (P = 0.01). CONCLUSIONS: The
      authors believe that the alveolar vascular pattern represented preexisting
      alveolar vessels, that is, the alveoli were filled up by tumor cells that
      exploited the existing highly vascular bed of the lungs. Therefore, this subgroup
      was characterized by tumor progression without the induction of angiogenesis. The
      current data do not support a significant prognostic role for tumor angiogenesis
      in patients who are diagnosed with NSCLC. This may have implications for therapy
      aimed at inhibiting tumor growth by the inhibition of angiogenesis.

PMID- 11301399
TI  - Neuroblastoma metastatic to the central nervous system. The Memorial Sloan
      kettering Cancer Center Experience and A Literature Review.
AB  - BACKGROUND: The central nervous system (CNS) can be a sanctuary site for cancer
      cells, because the blood-brain barrier impedes penetration of most
      chemotherapeutic agents. The authors hypothesized that, with improved survival
      from childhood metastatic neuroblastoma (NB), the incidence of CNS
      (intraparenchymal and leptomeningeal) spread may increase. They undertook this
      study to assess the frequency of CNS NB, to analyze risk factors and treatment
      options, and to review the literature. METHODS: The authors retrospectively
      analyzed all patients with metastatic NB who were treated on protocols N4, N5,
      N6, and N7 from 1980 to 1999 at Memorial Sloan-Kettering Cancer Center (MSKCC),
      during which time there was an increase in the overall survival rate. RESULTS:
      Two hundred fifty-one patients with Stage 4 NB (Group 251) were studied, of which
      127 (Group 127) were newly diagnosed patients who were treated initially at
      MSKCC. None had CNS NB at the time of diagnosis. Eleven patients developed
      documented CNS disease; 8 of these 11 recurrences were isolated in the CNS. For
      Group 127, the overall incidence rate of CNS NB was 6.3%, with an increase in
      incidence from N4-N5 to N6-N7 of from 1.7% to 11.7%. Seven patients had isolated
      CNS disease recurrences. Only lumbar punctures (LP) performed near the time of
      diagnosis in patients with known bone marrow involvement were associated with
      subsequent development of CNS disease. For the entire group of 251 patients,
      lumbar puncture at the time of diagnosis and elevated serum lactic dehydrogenase
      levels were prognostic. Among the larger series reported in the literature, CNS
      involvement from metastatic lesions was rare at the time of diagnosis and
      remained an uncommon complication. CONCLUSIONS: The incidence of CNS NB may be
      increasing. Because it is the sole site of disease recurrence in 64% of patients,
      the CNS may represent a sanctuary site for NB. CNS NB is associated with
      diagnostic lumbar punctures in patients with known bone marrow disease, raising
      the possibility that circulating or epidural microscopic tumor cells may seed the
      craniospinal axis.

PMID- 11301400
TI  - Earlier diagnosis of second primary melanoma confirms the benefits of patient
      education and routine postoperative follow-up.
AB  - BACKGROUND: Rising health care costs have caused providers to question the
      benefit of regular follow-up after treatment for patients with early stage
      cutaneous melanoma. The authors hypothesized that routine reassessment and
      careful education of these patients would facilitate earlier diagnosis of a
      subsequent second primary melanoma, as reflected by reduced thickness of that
      lesion. METHODS: A prospective melanoma data base was used to identify patients
      who developed a second primary melanoma after treatment for American Joint
      Committee on Cancer (AJCC) Stage I or II cutaneous melanoma. After excision of
      the initial primary melanoma, all patients underwent routine biannual follow-up
      for new primary lesions. Follow-up consisted of a questionnaire and a complete
      skin examination by a physician. In addition, patients were regularly educated
      regarding the increased risk of developing a second melanoma. A paired t test was
      used to examine AJCC stage, thickness, and level of invasion of the initial
      melanoma compared with the second primary melanoma. RESULTS: Of 3310 patients
      with AJCC Stage I or II melanoma, 114 patients (3.4%) developed a second primary
      melanoma. AJCC staging of both first and second melanomas was available in 82
      patients (72%). When the AJCC stages of first and second melanomas were compared,
      39 of 82 patients (48%) had lower stage second primary lesions, and 41 (50%) had
      same-stage second primary lesions. The mean tumor thickness was 1.32 +/- 1.02 mm
      for the initial melanoma, decreasing to 0.63 +/- 0.52 mm for the second melanoma;
      in fact, tumor thickness increased in only 4 of 51 patients (8%) whose records
      contained data for both first and second melanomas. Similarly, the level of
      invasion decreased in 60% of patients, remained the same in 27% of patients, and
      increased in only 13% of patients. By paired t test, the differences in AJCC
      stage, tumor thickness, and level of invasion between first and second melanomas
      were each highly significant (P = 0.0001). CONCLUSIONS: In this study, the second
      primary melanoma in patients with a prior cutaneous melanoma was significantly
      thinner than the initial primary lesion. This is evidence that careful follow-up
      and patient education allow earlier diagnosis. All patients diagnosed with
      cutaneous melanoma should be counseled regarding the risks of second melanoma and
      should undergo lifelong follow-up at biannual intervals.

PMID- 11301401
TI  - Serum endostatin levels are elevated in patients with soft tissue sarcoma.
AB  - BACKGROUND: Solid tumors are angiogenesis dependent, and elevated levels of
      proangiogenic cytokines have been reported in a variety of histologies.
      Endostatin is an antiangiogenic fragment of the basement membrane protein,
      collagen XVIII. Because antiangiogenic protein fragments may be generated by
      tumor-derived proteases, the authors sought to determine whether circulating
      levels of endostatin were elevated in patients with localized soft tissue
      sarcoma. METHODS: The authors analyzed preoperative serum levels of endostatin,
      vascular endothelial growth factor (VEGF), and basic fibroblast growth factor
      (bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with soft
      tissue sarcoma. For each serum sample, two aliquots were assayed in duplicate
      using a competitive enzyme immunoassay. Serum levels were compared with levels
      from 34 age-matched and gender-matched volunteer blood donors. RESULTS:
      Endostatin levels were significantly higher in sera from sarcoma patients than in
      sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, respectively; P = 0.0002;
      Mann-Whitney U test). Significant elevations also were noted in VEGF and bFGF
      levels (P = 0.0002 and P = 0.0001, respectively). Furthermore, endostatin levels
      > 2 standard deviations above the control mean (55 ng/mL) were associated with an
      increased risk of tumor recurrence after resection (P = 0.047; log-rank test).
      CONCLUSIONS: Serum endostatin, VEGF, and bFGF levels are elevated in patients
      with soft tissue sarcoma. Elevated endostatin levels appear to be associated with
      tumor aggressiveness. The role of these cytokines in sarcoma angiogenesis and as
      potential targets for therapy warrants further study.

PMID- 11301402
TI  - Systematic review of the diagnostic accuracy of (18)F-fluorodeoxyglucose positron
      emission tomography in melanoma patients.
AB  - BACKGROUND: Positron emission tomography (PET) with (18)F-fluorodeoxyglucose
      (FDG) is a rapidly developing new imaging technique in the diagnosis and staging
      of melanoma. The objective of the current study was to determine the diagnostic
      accuracy of FDG-PET in patients with melanoma. METHODS: A systematic review and
      meta-analysis of clinical studies regarding FDG-PET and cutaneous melanoma was
      conducted. Studies were identified by a comprehensive search of the MEDLINE,
      EMBASE, and Current Contents databases, without any language restrictions. Eleven
      studies were selected. The methodologic quality of these studies was assessed
      independently by two reviewers. Levels of evidence and grades of recommendation
      were determined for each study. Six studies could be included in the statistical
      pooling. Sources of heterogeneity were studied by meta-regression of the
      diagnostic odds ratio (DOR). A summary receiver operating characteristic curve
      was calculated. RESULTS: The pooled sensitivity and specificity of FDG-PET in the
      detection of melanoma metastases were 0.79 (95% confidence interval [95% CI],
      0.66-0.93) and 0.86 (95% CI, 0.78-0.95), respectively. The pooled DOR of 33.1
      (95% CI, 21.9-54.0) suggests a high diagnostic accuracy for PET. Subgroup
      analysis revealed that PET is more accurate for systemic staging (DOR of 36.4)
      than for regional staging (DOR of 19.5). When used for regional staging, PET
      performed better in patients with American Joint Committee on Cancer Stage III
      disease, compared with patients with Stage I and Stage II disease. However, the
      methodologic quality of the studies was limited. Major problems were
      verification, review, and selection bias. CONCLUSIONS: Due to the poor
      methodologic quality of the available studies, to the authors' knowledge it is
      yet not possible to develop guidelines for the effective use of PET in patients
      with melanoma. Future accuracy studies should meet the methodologic criteria
      outlined in the current review.

PMID- 11301403
TI  - A Phase II study of high-dose paclitaxel in patients with advanced neuroendocrine
      tumors.
AB  - BACKGROUND: New agents with antitumor activity in patients with neuroendocrine
      tumors are sorely needed. A Phase II study of high-dose paclitaxel in patients
      with metastatic carcinoid and islet cell tumors was performed at the Mayo Clinic.
      Granulocyte-colony-stimulating factor (GCSF) also was administered to ameliorate
      neutropenia. METHODS: Twenty-four patients (14 with carcinoid tumors, 9 with
      islet cell tumors, and 1 with an anaplastic tumor) were enrolled on this Phase II
      study of paclitaxel given as a 24-hour continuous infusion at a dose of 250
      mg/m(2) every 3 weeks plus GCSF at a dose of 5 microg/kg/day subcutaneously,
      beginning 24 hours after the completion of the paclitaxel dose and continuing
      until the absolute neutrophil count was > 10,000/microL. RESULTS: All 24 patients
      were evaluable for analysis. The overall response rate was 8% (95% confidence
      interval [95% CI], 0-0.11). At last follow-up all patients except 1 had developed
      disease progression, with an estimated median time to disease progression of 3.2
      months (95% CI, 1.6-6.0 months). The estimated median survival was 1.5 years (95%
      CI, 1.0-1.8 years). Hematologic toxicity was significant with 12 of 24 patients
      developing Grade 4 (according to the National Cancer Institute Common Toxicity
      Criteria scale) neutropenia; however, there were no septic deaths reported. There
      were 17 episodes of Grade 4 neutropenia in these 12 patients and the duration of
      these events ranged from 2-5 days. More common nonhematologic toxicities included
      arthralgia (21 patients), anorexia (15 patients), nausea (15 patients), diarrhea
      (12 patients), and allergic reactions (2 patients). CONCLUSIONS: Given the lack
      of antitumor activity of paclitaxel and the significant hematologic toxicity
      observed despite the use of GCSF support in the current study cohort of patients
      with neuroendocrine tumors, further studies of this combination in this
      particular patient population are not recommended.

PMID- 11301404
TI  - A Phase I study of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-1,3-dioxolane]
      platinum(II) in patients with advanced malignancies.
AB  - BACKGROUND: A Phase I study of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-1,3
      dioxolane] platinum(II) (SKI 2053R), a new platinum derivative, was performed to
      determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLTs),
      and the pharmacokinetic profile of SKI 2053R in patients with advanced,
      refractory malignancies. METHODS: Twenty-one patients were entered into the
      study. SKI 2053R was administered with an intravenous infusion over 1 hour every
      4 weeks. The SKI 2053R dose was escalated from 40 mg/m(2) up to 480 mg/m(2) using
      a modified Fibonacci scheme. Pharmacokinetic analysis was done in all patients to
      determine the total and ultrafiltrable platinum concentrations in both the plasma
      and the urine. RESULTS: All patients were evaluable for toxicity and response.
      There was no significant toxicity with dosages up to 360 mg/m(2). At 480 mg/m(2),
      two of three patients developed Grade 4 hepatotoxicity, Grade 3 leukopenia and
      thrombocytopenia, and Grade 2 azotemia and proteinuria. Other toxicity included
      nausea and emesis, but it was controlled with antiemetics. SKI 2053R did not
      cause significant neurotoxicity or mucositis. There were 4 patients with stable
      disease among the 21 patients. Plasma decay of the total and free platinum
      concentrations was best fitted by using a two-compartment, open model. The
      terminal plasma half-life of the total platinum after SKI 2053R administration
      ranged from 63.4 hours to 114.1 hours in dosages ranging from 40 mg/m(2) to 480
      mg/m(2) without significant dose dependency. However, the terminal plasma half
      life of the free platinum concentration showed a significant dose dependent,
      incremental pattern. The renal excretion of SKI 2053R measured as platinum ranged
      from 49% to 75% of the administered dose. CONCLUSIONS: The MTD of SKI 2053R was
      480 mg/m(2). The major DLTs were hepatotoxicity, nephrotoxicity, and
      myelosuppression. The recommended starting dose for a subsequent Phase II study
      is 360 mg/m(2) once every 4 weeks.

PMID- 11301405
TI  - Prognostic features and outcome in patients with diffuse large B-cell lymphoma
      who do not achieve a complete response to first-line regimens.
AB  - BACKGROUND: The current study was conducted to analyze the outcome and prognostic
      factors of patients with diffuse large B-cell lymphoma (DLCL) who did not achieve
      a complete response (CR) to first-line treatment. METHODS: The current study was
      comprised of 83 patients (43 males and 40 females with a median age of 62 years)
      who did not achieve a CR (58 of whom had primary refractory disease and 25 of
      whom achieved a partial response) with initial treatment (doxorubicin-containing
      regimens in 87% of cases) from a series of 239 patients consecutively diagnosed
      with DLCL at a single institution. Initial variables, response to therapy, and
      salvage treatment were analyzed to predict survival. RESULTS: Compared with
      patients who achieved a CR, nonresponders or partial responders more frequently
      were of advanced age and had a poor performance status (PS), B-symptoms, advanced
      stage of disease, bone marrow infiltration, increased serum lactate
      dehydrogenase, and a high-risk International Prognostic Index. Among the 58
      patients with primary refractory disease, 18 died during initial treatment due to
      toxicity (14 patients) or disease progression (4 patients). The main variables
      predicting early death were a poor PS, age > 60 years, and an immunoblastic DLCL
      subtype. Twenty-five of these 58 patients were able to receive salvage regimens,
      with only 1 of them achieving a CR. The median survival for this group of
      patients was 10 months. With regard to those patients achieving a partial
      response, 18 of the 25 patients received further therapy with 28% of them
      achieving a CR. The median survival was 23 months. The degree of the response was
      found to be the only significant variable with which to predict survival, with 2
      year survival rates of 4% and 40%, respectively, for patients with primary
      refractory disease and patients who achieved a partial response. CONCLUSIONS: The
      prognosis of patients with primarily refractory DLCL is extremely unfavorable,
      whereas that of patients who achieve a partial response is slightly better. The
      inclusion of these patients in experimental trials is limited due to their
      tendency to be of an older age and to have a poor general status.

PMID- 11301406
TI  - Oral ciprofloxacin in the management of children with cancer with lower risk
      febrile neutropenia.
AB  - BACKGROUND: Recent reports and a previous randomized trial conducted at the
      authors' institution suggested that a lower risk subset of children with febrile
      neutropenia under chemotherapy might benefit of an oral antibiotic outpatient
      approach. METHODS: The objective of this study was to test the efficacy of oral
      ciprofloxacin in the treatment of lower risk febrile neutropenia (LRFN) in
      children treated for malignant diseases. From November 1998 to December 1999, 93
      episodes of LRFN in 87 children (median age, 5.5 years; range, 0.9-15.8 years)
      were included in a prospective randomized controlled single institution trial.
      Inclusion criteria included fever (> 38 degrees C), severe neutropenia (absolute
      neutrophil count, < 500/mm(3)), and lower risk features (e.g., absence of severe
      comorbidity factors, good clinical condition, negative blood cultures, control of
      local infection, prediction of a period of neutropenia less than 10 days after
      admission, and compliant parents). After 24 hours of a single intravenous
      ceftriaxone (100 mg/kg) plus amikacin (15 mg/kg) and completed risk assessment
      workup, patients were discharged and randomly allocated to two groups. Group A
      (48 episodes) received ciprofloxacin 20 mg/kg/day orally (p.o.) every 12 hours
      for 6 days. Group B (45 episodes) received intravenous ceftriaxone plus amikacin
      for 2 days more followed by cefixime (8 mg/kg/day p.o.) every 24 hours for 4
      additional days. Failure was defined as the need of a second hospitalization
      during the same episode. RESULTS: Most of the patients (59% in Group A and 52% in
      Group B) were treated for malignant solid tumors. Fifteen (31%) children in Group
      A and 15 (33%) in Group B presented with fever of unknown origin (P value was not
      significant). No significant differences were found in sites of initial infection
      between both groups. Overall results in this study were excellent. Only one
      patient with respiratory failure was detected in Group B, who did well with
      secondary treatment. CONCLUSIONS: In febrile neutropenic children after
      anticancer therapy and lower risk features, oral ciprofloxacin for 6 days after
      24 hours of intravenous ceftraxione plus amikacin appears to be as efficacious as
      intravenous ceftriaxone plus amikacin for 2 days more followed by cefixime for 4
      additional days. These results contribute to strengthen the concept of LRFN.

PMID- 11301407
TI  - Molecular detection of metastatic retinoblastoma cells by reverse transcription
      polymerase reaction for interphotoreceptor retinoid-binding protein mRNA.
AB  - BACKGROUND: In the current study, the authors report a 4 year old girl with
      disseminated retinoblastoma. To find sensitive and specific molecular markers for
      detection of retinoblastoma cells in blood and marrow, the authors evaluated
      three photoreceptor-associated gene transcripts by using reverse transcription
      polymerase chain reaction (RT-PCR). METHOD: Samples of bone marrow and blood were
      obtained from healthy donors and the patient. RT-PCR was performed to detect the
      cone alpha'-subunit of cGMP phosphodiesterase (cone alpha'-PDE), the rod beta
      subunit of cGMP (rod beta-PDE), and the interphotoreceptor retinoid-binding
      protein (IRBP) gene transcript in RNA extracted from the samples. RESULTS: While
      no expression of rod beta-PDE or IRBP was detected in any of the normal samples,
      expression of cone alpha'-PDE was detected in two out of seven normal marrow
      samples. Expression of rod beta-PDE was not detected in the patient samples.
      Expression of IRBP was detected in the patient samples obtained from iliac bone
      marrow before intensive chemotherapy but not thereafter. CONCLUSION: RT-PCR for
      IRBP was a useful method for detecting metastatic retinoblastoma cells as well as
      for evaluating the therapeutic effects of treatment in this particular case.

PMID- 11301408
TI  - Hospital volume and hospital mortality for esophagectomy.
AB  - BACKGROUND: Hospital mortality after esophagectomy has decreased from 29% to 7.5%
      over the last decades because of improved surgical techniques and better
      perioperative care. Suggestions have been made that a further decrease in
      hospital mortality may be achieved by centralization of esophagectomies in high
      volume centers. METHODS: The effect of hospital volume on hospital mortality
      after esophagectomy in the Netherlands was analyzed based on data from the Dutch
      National Medical Registry and the Dutch Network and National Database for
      Pathology over the period 1993-1998. RESULTS: Annually, approximately 310 (range,
      264-321) esophagectomies are performed in the Netherlands. Fifty-two percent are
      performed in 43-55 low volume centers (1-10 resections a year). Six percent are
      performed in 1-3 medium volume centers (11-20 resections a year). The remainder
      (42%) is performed in two high volume centers (> 50 resections a year). Hospital
      mortality is 12.1%, 7.5% and 4.9% respectively (P < 0.001). The high volume
      centers seem to see slightly more advanced tumors than the low and medium volume
      centers. CONCLUSIONS: There is a significant (inverse) relation between hospital
      mortality and hospital volume for esophageal resection in the Netherlands.
      Although hospital mortality is not the only measure for quality of care, these
      data suggest a potential beneficial effect to centralization of esophagectomy in
      the Netherlands.

PMID- 11301409
TI  - Epstein-Barr virus and survival after Hodgkin disease in a population-based
      series of women.
AB  - BACKGROUND: Epstein-Barr virus (EBV) positive Hodgkin disease (HD), as defined by
      the presence of EBV genes or gene products in the malignant cells, differs
      epidemiologically from EBV negative HD. However, survival patterns for EBV
      defined HD have not been well studied. To determine if EBV status influenced
      survival time after HD, the authors investigated a large, population-based series
      of female patients. METHODS: For 311 female patients living in the Greater San
      Francisco Bay Area who were aged 19-79 years with HD diagnosed between mid-1988
      and 1994, histopathologically rereviewed archived biopsy specimens were assayed
      for EBV with immunohistochemistry and in situ hybridization. The 53 subjects with
      EBV positive and the 258 with EBV negative HD were observed for vital status
      through 1998; overall survival was analyzed with Kaplan-Meier and Cox
      proportional hazards regression methods. RESULTS: Epstein-Barr virus positive HD
      patients were older, received diagnosis at a later stage, and were less likely to
      have nodular sclerosis histology than EBV negative patients. Deaths were reported
      for 21 (40%) EBV positive and 37 (14%) EBV negative patients. No survival
      differences were observed between EBV positive and negative women aged 19-44
      years, but survival was significantly poorer in women aged 45-79 years with EBV
      positive HD. Regression analysis confirmed this strong negative effect of EBV
      positive status on survival (hazard ratio for death, 3.0; 95% confidence
      interval, 1.5-6.2) as unrelated to age, stage at diagnosis, or tumor histology.
      CONCLUSIONS: This study found a marked survival disadvantage for EBV positive HD
      in older but not young adult women. These findings suggest influences of both EBV
      status and age on HD survival, as well as pathogenesis.

PMID- 11301410
TI  - Cyclopentenone prostaglandins: new insights on biological activities and cellular
      targets.
AB  - The cyclopentenone prostaglandins PGA2, PGA1, and PGJ2 are formed by dehydration
      within the cyclopentane ring of PGE2, PGE1, and PGD2. PGJ2 is metabolized further
      to yield Delta(12)-PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). Various
      compounds within the cyclopentenone prostaglandin family possess potent anti
      inflammatory, anti-neoplastic, and anti-viral activity. Most actions of the
      cyclopentenone prostaglandins do not appear to be mediated by binding to G
      protein coupled prostanoid receptors. Rather, the bioactivity of these compounds
      results from their interaction with other cellular target proteins. 15-deoxy
      Delta(12,14)-PGJ(2) is a high affinity ligand for the nuclear receptor PPARgamma
      and modulates gene transcription by binding to this receptor. Other activities of
      the cyclopentenone prostaglandins are mediated by the reactive alpha,beta
      unsaturated carbonyl group located in the cyclopentenone ring. The transcription
      factor NF-kappaB and its activating kinase are key targets for the anti
      inflammatory activity of 15d-PGJ2, which inhibits NF-kappaB-mediated
      transcriptional activation by PPARgamma-dependent and independent molecular
      mechanisms. Other cyclopentenone prostaglandins, such as Delta(7)-PGA1 and
      Delta(12)-PGJ2, have strong anti-tumor activity. These compounds induce cell
      cycle arrest or apoptosis of tumor cells depending on the cell type and treatment
      conditions. We review here recent progress in understanding the mechanisms of
      action of the cyclopentenone prostaglandins and their possible use as therapeutic
      agents.

PMID- 11301411
TI  - Orbofiban: an orally active GPIIb/IIIa platelet receptor antagonist.
AB  - A key role has been established for platelet activation and thrombus formation in
      the pathogenesis of acute coronary syndromes, and restenosis after percutaneous
      interventions. Antiplatelet agents that have a wider spectrum of activity than
      aspirin, and clopidogrel would be expected to provide improved antithrombotic
      protection. Preclinical studies were used to predict clinical efficacy of orally
      active GPIIb/IIIa antagonists such as xemilofiban, sibrafiban, lefradafiban, and
      orbofiban. While clinical trials have shown potent and sustained platelet
      inhibition, outcomes of trials with these first generation GPIIb/IIIa compounds
      have been disappointing. The active moiety of orbofiban is a potent and specific
      inhibitor of fibrinogen binding to GPIIb/IIIa, leading to inhibition of platelet
      aggregation to a wide variety of agonists. Studies comparing inhibition of
      aggregation and bleeding suggest that chronic inhibition of platelet aggregation
      can be achieved without major bleeding side effects. Thrombus formation is
      prevented in canine models of thrombosis. Orbofiban is approximately 28%
      bioavailable with a t(1/2) of 18 hr. The high bioavailability, long half-life,
      and potential safety suggest orbofiban would be suitable for chronic oral
      administration. Clinical data demonstrate that orally administered orbofiban has
      the desired pharmacodynamic effect of inhibiting platelet aggregation but does
      not demonstrate clinical benefit when examined in large-scale trials.

PMID- 11301412
TI  - Recent strategies in the development of new human cytomegalovirus inhibitors.
AB  - Human cytomegalovirus (HCMV) is one of the most common opportunistic infections
      in immunucompromised individuals, such as AIDS patients and organ transplant
      recipients, and is the most frequent congenital viral infection in humans.
      Despite a reduction of the incidence of AIDS-related opportunistic infections in
      patients under highly active antiretroviral treatment, attention should be paid
      to the HCMV risk factor in these individuals. Furthermore, HCMV may have an
      important role in atherosclerosis. Existing antiviral treatments for the HCMV
      infection suffer from poor bioavailability, toxicity, and limited effectiveness,
      mainly due to the development of drug resistance. Fortunately there are novel and
      potentially very effective new compounds undergoing pre-clinical and clinical
      evaluation. This review provides an overview in the last five years of new HCMV
      inhibitors (chemical structures, SAR, and new mechanisms of action) with the aim
      to provide new clues for the development of future drugs against this
      opportunistic virus.

PMID- 11301413
TI  - Genotoxicity of di-butyl-phthalate and di-iso-butyl-phthalate in human
      lymphocytes and mucosal cells.
AB  - The genotoxicity of phthalates, widely used plasticizers, has been shown
      previously for di-butyl-phthalate (DBP) and di-iso-butyl-phthalate (DBP) in human
      mucosal cells of the upper aerodigestive tract in a previous study using the
      Comet assay. Furthermore, higher genotoxic sensitivities of patients with
      squamous cell carcinomas of either the larynx or the oropharynx compared to non
      tumor patients were described. Other authors have demonstrated DNA damage by a
      different phthalate in human lymphocytes. It was the aim of the present study to
      determine whether there is a correlation between the genotoxic sensitivities to
      DBP and its isomer DiBP in either mucosal cells or lymphocytes. The single-cell
      microgel electrophoresis assay (Comet assay) was applied to detect DNA strand
      breaks in human epithelial cells of the upper aerodigestive tract (n=132
      specimens). Human mucosa was harvested from the oropharynx in non-tumor patients
      and patients with squamous cell carcinomas of the oropharynx. Laryngeal mucosa of
      patients with laryngeal squamous cell carcinomas was harvested as well.
      Peripheral lymphocytes (n=49 specimens) were separated from peripheral blood.
      Xenobiotics investigated were DBP, DiBP, and N'methyl-N'-nitro-N-nitrosoguanidine
      (MNNG) as positive control, respectively. For statistical analysis, the SPSS
      correlation analysis according to Pearson and the Wilcoxon test were performed.
      Genotoxicity was found for DBP and DiBP in epithelial cells and lymphocytes
      (P<0.001). MNNG caused severe DNA damage. In analyzing DBP and DiBP results,
      genotoxic impacts in mucosal cells showed an intermediate correlation (r=0.570).
      Correlation in lymphocytes was the same (r=0.570). Phthalates have been
      investigated as a potential health hazard for a variety of reasons, including
      possible xenoestrogenic impact, peroxisome proliferation, and membrane
      destabilization. The present investigation suggests a correlated DNA-damaging
      impact of DBP and DiBP in human mucosal cells and in lymphocytes, respectively.

PMID- 11301414
TI  - Embryolethality induced by metronidazole (MTZ) in Rattus norvegicus.
AB  - Parasitic illnesses is increasing all over the world, especially in developing
      countries, and metronidazole (MTZ) is the therapeutic agent usually administered
      to children as well as adults at the reproductive age. In this work, we propose
      an evaluation of MTZ in order to analyze the potential reproductive damage in
      females by using Rattus norvegicus (Sprague-Dawley) as an animal model. Adult
      female rats were mated after MTZ treatments, and they were sacrificed at 21 days
      of gestation. Different types of damage were evaluated by using mortality,
      phenotypic abnormalities and reproductive capacity as parameters, and were
      studied and scored in 70 adult specimens (450 g/bw). They were divided into five
      groups: a) untreated females as a control group; females treated with b) DMSO as
      a solvent control group or c) 500 mg/kg/bw of MTZ per day for 7 days as
      therapeutic dose (TD); d) a half therapeutic dose (HD); and e) a double
      therapeutic dose (DD). Pre-implantation death in MTZ-treated groups was not
      significantly different from controls. However, drug treatments significantly
      increased the frequency of post-implantation deaths and the dominant lethals were
      ranged between 12.0 % and 17.8 %.

PMID- 11301415
TI  - Sister chromatid exchange induced by several types of coffees in Chinese hamster
      ovary cells.
AB  - Different brands of commercial caffeinated and decaffeinated coffees (roasted,
      high roast, blend ground, and instant coffees) were studied. These coffees were
      tested for their ability to induce sister chromatid exchanges (SCE) in CHO-K1
      cells. Tests were performed in the presence and in the absence of a metabolic
      activation system (S-9 mix). Results were compared to the roasting procedure
      because genotoxic products could be formed from these processes. Our results
      indicate that caffeinated instant coffees showed higher genotoxic activity than
      decaffeinated coffees. Non-significant genotoxic activity was detected with the
      green coffee (unroasted). The highest increase of the frequency of SCE occurred
      when the caffeinated instant coffee was tested in the absence of metabolic
      activation system. The repeatability of the test was checked through three assays
      with the same sample.

PMID- 11301416
TI  - Oral administration of clomiphene to neonatal rats causes reproductive tract
      abnormalities.
AB  - Oral administration of clomiphene at 2, 4, or 8 mg/kg to 4-day-old rats caused
      multiple histopathological abnormalities of the reproductive tract in both male
      and female animals. No histopathological abnormalities were observed in 30-day
      old male rats at any dose examined. In contrast, 30-day-old females showed
      hypertrophy of the myometrium at all doses examined, and hypertrophy of the
      luminal or glandular epithelium, and dilatation of the uterine lumen were
      observed in the highest dose group. In post-pubertal rats, histopathologically
      marked changes were observed in the testes and epididymides in males, and in the
      ovaries and uterus in females in the highest dose group. In addition, relative
      weight of male reproductive organs in the highest dose group was decreased as
      compared with that in the controls. These results suggested that early neonatal
      exposure to clomiphene induced marked reproductive tract abnormalities in males
      after puberty, as well as in females.

PMID- 11301417
TI  - Possible prevention by abieslactone of development of diethylnitrosamine
      initiated GST-P positive foci in the rat liver.
AB  - Triterpenoid compounds, isolated from plants of Abies genus (Pinceae), are known
      to exert anti-tumor promotion activities in mouse skin carcinogenesis. In the
      present study, we investigated whether AVB-1 and acid and acid methyl ester
      derivatives have inhibitory effects on rat hepatocarcinogenesis by using a liver
      medium-term bioassay for carcinogens (Ito's test), immunohistochemically
      assessing the numbers and areas per cm(2) of preneoplastic lesions, glutathione S
      transferase placental form (GST-P)-positive foci. In experiment 1, 6-week-old
      male Fisher 344 rats were given a single intraperitoneal injection of
      diethylnitrosamine (200 mg/kg b.w.) and subjected to two-thirds partial
      hepatectomy at week 3. From weeks 2 to 8, the compounds were given three times a
      week at a dose of 1 mg/kg b.w. by i.g. gavage and found to significantly decrease
      the number of GST-P-positive foci in the liver. In experiment 2, AVB-1 was given
      three times a week at doses of 3, 1, or 0.3 mg/kg b.w. by i.g. gavage from weeks
      2 to 8. All doses of AVB-1 significantly decreased the numbers of GST-P-positive
      foci. Thus, our results suggest that AVB-1 is a chemopreventive agent for rat
      hepatocarcinogenesis.

PMID- 11301418
TI  - Assessment of DNA damage in spleen, bone marrow, and peripheral blood from
      malnourished rats by single cell gel electrophoresis assay.
AB  - Severe malnutrition is widely distributed throughout the world and exhibits a
      high prevalence in developing countries. Experimental malnutrition models have
      been useful to study the effects of malnutrition at early ages. The purpose of
      this study was to determine if severe malnutrition induced during lactation in
      rats increases DNA damage in spleen, peripheral blood, and bone marrow cells, as
      well as in isolated lymphocytes or lymphoid cells from the same tissues. These
      cells were obtained from malnourished rats at weaning (21 days of age). DNA
      damage was estimated by using the alkaline single cell electrophoresis assay. The
      results obtained in this study indicate that malnutrition is associated with a
      significant increase in DNA damage in all cell types that were studied in
      malnourished rats. The analysis of the length of DNA migration and dispersion
      coefficient showed that some cell types were more susceptible to DNA damage
      related with malnutrition. The damage observed could be due to the deficiency of
      several essential nutrients required for protein synthesis that are associated
      with DNA integrity, impaired DNA repair mechanisms, and/or to the unavailability
      of molecules necessary to protect the cells against DNA oxidative damage. This
      damage may produce negative effects for the further development of the organism,
      since bone marrow is the main site of hematopoiesis and spleen is an important
      lymphopoietic organ. Also, the increased level of DNA damage in peripheral blood
      lymphocytes and leukocytes could be related to negative effects such as a
      deficient immune response.

PMID- 11301421
TI  - Electrochemical Surface Science This manuscript is based on the Bonhoeffer-Eucken
      Scheibe lectures of the Deutsche Bunsengesellschaft, given by the author at
      Erlangen, Berlin, and Leipzig in 1999/2000. 
AB  - The last 30 years have seen remarkable changes in interfacial electrochemistry,
      particularly in the kind of questions that were addressed in electrochemical
      studies. Ever since classical surface science, traditionally performed under
      ultrahigh vacuum conditions, has succeeded in describing surfaces and surface
      reactions on a molecular level, electrochemists longed for a microscopic
      understanding of the solid/electrolyte interface and, at the same time, searched
      widely for new experimental ways to reach that goal. Herein, studies are
      described concerning the structure and the dynamics of bare and adsorbate-covered
      electrode surfaces and of metal deposition as a simple, yet important,
      electrochemical process. In all these cases, the scanning tunneling microscope
      plays a pivotal role emphasizing the surface-science approach to the problems.

PMID- 11301423
TI  - New Cages and Unusual Guests: Fullerene Chemistry Continues To Excite.

PMID- 11301422
TI  - From the Metal to the Molecule-Ternary Bismuth Subhalides.
AB  - Subvalent compounds, that is, metal-rich substances in which the average
      oxidation state of the cation is smaller than would be expected from the (8-N)
      rule, have proved to be a rich source of unexpected structural and physical
      features. The extraordinary structural chemistry generally observed in subvalent
      compounds is a consequence of the low and often non-integer oxidation states of
      the metal atoms coupled with the low concentration of valence electrons. Both
      factors can lead to a wide-range of bonding types within the same compound. A
      characteristic of these compounds is the interplay between "metallic" regions,
      with delocalized electrons and mainly nonpolar bonds between the metal atoms, and
      "saltlike" regions, which are characterized by strong localization of the
      electrons and heteropolar exchange between the metal and nonmetal atoms. The
      volumes of the different structural regions as well as the extent to which they
      interpenetrate can vary from compound to compound. The ternary subhalides of
      bismuth belong to a new class of substances which cover the whole spectrum from
      partially oxidized "porous" metals, through one- and two-dimensional metals, up
      to semiconducting ionic or molecular cluster compounds. These subvalent compounds
      with their unusually high chemical stabilities provide excellent vehicles for
      further research and their potential is described in the following article.

PMID- 11301424
TI  - Highly Enantioselective or Not?-Chiral Monodentate Monophosphorus Ligands in the
      Asymmetric Hydrogenation.

PMID- 11301425
TI  - Kekule Escapes, Popper As Well.

PMID- 11301426
TI  - Reply.

PMID- 11301427
TI  - Metal Oxide Containing Mesoporous Silica with Bicontinuous "Plumber's Nightmare"
      Morphology from a Block Copolymer-Hybrid Mesophase This work was supported by the
      National Science Foundation (DMR-0072009), the Cornell Center for Materials
      Research (NSF DMR-9632275), and the Department of Energy (DE-FG02-97ER62443). We
      also acknowledge very helpful discussions with G. E. S. Toombes. 

PMID- 11301428
TI  - Solvent-Free, Low-Temperature, Selective Hydrogenation of Polyenes using a
      Bimetallic Nanoparticle Ru-Sn Catalyst We thank Dr. R. G. Bell for assistance
      with the computer graphics, Drs. P. A. Midgeley, V. Keast, and M. Weyland for
      help with STEM, and gratefully acknowledge the support (via a rolling grant to
      J.M.T. and an award to B.F.G.J.) of EPSRC and the award of a research fellowship
      (for G.S.) from the Leverhulme Foundation and a Marie Curie Fellowship within the
      TMR Programme of the European Commission (for S.H.). 

PMID- 11301429
TI  - Slow Shuttling in an Amphiphilic Bistable

PMID- 11301430
TI  - Isolation of an Acid/Base Complex in Solution Puts the Brakes on Nitrogen
      Inversion We are grateful for financial support from the Skaggs Research
      Foundation and the National Institutes of Health. We are pleased to acknowledge
      advice from Professors Stephen Craig and Dmitry Rudkevich.

PMID- 11301431
TI  - Isolation and Structural Characterization of the Endohedral Fullerene
      Sc(3)N@C(78) This work was supported by the US National Science Foundation
      (Grants CHE 9610507 and CHE 0070291 to A.L.B.), LUNA Innovations (H.C.D.), and
      the Gulbenkian Foundation (postdoctoral fellowship to A.d.B.-D.). 

PMID- 11301432
TI  - Antitumor trans Platinum Complexes can Form Cross-Links with Adjacent Purine
      Groups Financial support by the European Commission BIOMED II program (Contract
      BMH4-CT97-2485) and COST (D8/007/97 and D8/012/97) are gratefully acknowledged.
      Thanks are extended to the Norwegian Research Council (Contract 135055/410), the
      University of Bari, the Ministero dell'Universita e della Ricerca Scientifica e
      Tecnologica, MURST (Cofin. 1988 no. 9803021072), and the Consiglio Nazionale
      delle Ricerche, CNR (Roma) for financial support. 

PMID- 11301433
TI  - Molecular Modulation of Surfactant Aggregation in Water: Effect of the
      Incorporation of Multiple Headgroups on Micellar Properties This work was
      supported by a grant from the Inter University Consortium. S. B. is the
      Swarnajayanti Fellow of the Department of Science and Technology. 

PMID- 11301434
TI  - R$?rm{^{{?ast}}_{4}}$Tl(3)Cl and R$?rm{^{{?ast}}_{6}}$Tl(6)Cl(2) (R*=SitBu(3))
      The First Compounds with Larger Clusters Containing Covalently Linked Thallium
      Atoms Compounds of Silicon, Part 143. Supersilyl Compounds of Boron and Its
      Homologues, Part 12. This work was supported by the Deutsche
      Forschungsgemeinschaft and by the Fonds der Chemischen Industrie. Part 42: N.
      Wiberg, W. Niedermayer, J. Organomet. Chem. 2001, in press; Part 11. M. Kehrwald,
      W. Kostler, A. Rodig, G. Linti, T. Blank, N. Wiberg, Organometallics 2001, in
      press. 

PMID- 11301435
TI  - New C(2)-Symmetrical 1,2-Diphosphanes for the Efficient Rhodium-Catalyzed
      Asymmetric Hydroboration of Styrene Derivatives We thank the Deutsche
      Forschungsgemeinschaft (Leibniz program), The Institut de Recherches Servier
      (Suresnes, France), and PPG-SIPSY for financial support. We thank also BASF AG
      (Ludwigshafen), Chemetall GmbH (Frankfurt), and Degussa-Huls AG (Hanau) for the
      generous gift of chemicals. 

PMID- 11301436
TI  - The First Crystallographic Evidence for the Structures of ortho-Lithiated
      Aromatic Tertiary Amides This work was supported by the UK EPSRC (M.A.H.), and
      St. Catharine's (R.P.D.) and Gonville & Caius (A.E.H.W.) Colleges, Cambridge. 

PMID- 11301437
TI  - A Ga(8)R(6) Cluster as an Ideal Model for a Metal-Metal Bond? This work was
      supported by the Deutsche Forschungsgemeinschaft and by the Fonds der Chemischen
      Industrie. 

PMID- 11301438
TI  - Haag-Dessau Catalysts for Ring Opening of Cycloalkanes.

PMID- 11301439
TI  - Tris(azolyl)methylthiolates: Another New Scorpionate Class?

PMID- 11301440
TI  - Dianionic Iron and Ruthenium(2-) Biphosphinine Complexes: A Formal d(10)
      Ruthenium Complex with a Square Planar Geometry This work was supported by the
      CNRS, the Ecole Polytechnique, and University Paris XI Orsay. 

PMID- 11301441
TI  - Stepwise Building of Polyphosphirene Chains.

PMID- 11301442
TI  - Steam-Stable MSU-S Aluminosilicate Mesostructures Assembled from Zeolite ZSM-5
      and Zeolite Beta Seeds The partial support of this research by the National
      Science Foundation through CRG grant 99-03706 is gratefully acknowledged. 

PMID- 11301443
TI  - Strongly Acidic and High-Temperature Hydrothermally Stable Mesoporous
      Aluminosilicates with Ordered Hexagonal Structure This work was supported by the
      National Natural Science Foundation of China (No. 29825108), the State Basic
      Research Project, and the National Advanced Materials Committee of China. We
      thank Prof. Ruren Xu, Dr. Haiping Sun, Prof. Bensan Zou, Prof. Ze Zhang, and
      Professor Osamu Tarasaki for helpful suggestions, discussions, and transmission
      electron microscopy experiments. 

PMID- 11301444
TI  - Synthesis of the FGHI Ring System of Azaspiracid We thank Dr. D. H. Huang and Dr.
      G. Siuzdak for NMR spectroscopic and mass spectrometric assistance, respectively.
      Financial support for this work was provided by The Skaggs Institute for Chemical
      Biology, the National Institutes of Health (USA), a predoctoral fellowship from
      Bristol-Myers Squibb (F.B.), postdoctoral fellowships from the Academy of
      Finland, the Ella and Georg Ehrnrooth Foundation, and the Tauno Tonning
      Foundation (all to P.M.P.), ArrayBiopharma (N.Z.), and Bayer AG (N.D.), and
      grants from Abbott, Amgen, ArrayBiopharma, Boehringer-Ingelheim, Glaxo, Hoffmann
      LaRoche, DuPont, Merck, Novartis, Pfizer, and Schering Plough. 

PMID- 11301445
TI  - Synthesis of a Cp* Complex of Tungsten with Three Different Chalcogenido (O(2-),
      S(2-), and Se(2-)) Ligands We thank Prof. Roger E. Cramer for careful reading of
      the manuscript; Cp=C(5)Me(5). 

PMID- 11301446
TI  - Combination of Electrografting and Ring-Opening Metathesis Polymerization: An
      Efficient Way to Prepare Polynorbornene Brushes on Conducting Substrates The
      authors thank the "Services Federaux des Affaires Scientifiques, Techniques et
      Culturelles" for general support under the auspices of the "Poles d'Attraction
      Interuniversitaires: Supramolecular Catalysis and Supramolecular Chemistry". C.J.
      is "Charge de Recherche" at the "Fonds National pour la Recherche Scientifique"
      (FNRS). 

PMID- 11301447
TI  - The First Quadruple Bond Between Elements of Different Groups This work was
      supported by the National Science Foundation (Grant CHE-9612725) and a Stanford
      Graduate Fellowship (R.B.). We thank Dr. F. Hollander (Berkeley), A. Cole
      (Stanford), and Dr. K. Hubler (Stuttgart) for acquiring or for assistance in the
      initial processing of the X-ray data. 

PMID- 11301448
TI  - Synthesis of the Globo H Hexasaccharide Using the Programmable Reactivity-Based
      One-Pot Strategy This research was supported by the National Institutes of
      Health. F.B. thanks the Deutsche Forschungsgemeinschaft for a fellowship. 

PMID- 11301449
TI  - Synthesis of alpha,beta-Unsaturated Amides by Olefin Cross-Metathesis The authors
      would like to thank the National Institutes of Health for generous support of
      this research, and D. Benitez, C. Bielawski, Dr. S. D. Goldberg, Dr. C. W. Lee,
      J. P. Morgan, and M. S. Sanford for helpful discussions. 

PMID- 11301450
TI  - The First Ce(IV) Metallasilsesquioxane Complex:

PMID- 11301451
TI  - Differential Cleavage of Arylmethyl Ethers: Reactivity of 2,6-Dimethoxybenzyl
      Ethers Financial support was provided by the Robert A. Welch Foundation, NIH
      (GM31278, DK38226), CNRS, Instituts de Recherche Pierre Fabre (to R.B.), and an
      unrestricted grant from Taisho Pharmaceutical Co., Ltd. We thank Dr. Naoya Ono
      for helpful discussions. 

PMID- 11301452
TI  - Indoloparacyclophanes: Synthesis and Dopamine Receptor Binding of a Novel
      Arylbioisostere This work was supported by the Fonds der Chemischen Industrie. 

PMID- 11301453
TI  - Nickel-Catalyzed Highly Regio- and Stereoselective Cyclization of Oxanorbornenes
      with Alkyl Propiolates: A Novel Method for the Synthesis of Benzocoumarin
      Derivatives We thank the National Science Council (NSC 89-2119-M-007-010) and the
      Ministry of Eduction (89-FAO4-AA) of the Republic of China for support of this
      research. 

PMID- 11301454
TI  - Copper(I) Carbenes: The Synthesis of Active Intermediates in Copper-Catalyzed
      Cyclopropanation B.F.S. thanks the Fonds der Chemischen Industrie for a doctoral
      fellowship. 

PMID- 11301455
TI  - Unusual Palladium-Catalyzed Cascade Arylation of alpha,beta-Unsaturated Phenyl
      Sulfones under Heck Reaction Conditions Financial support for this work by the
      Ministerio de Educacion y Cultura (DGES, project PB96-0021), Ministerio de
      Ciencia y Tecnologia (project BQU2000-0226), and Comunidad de Madrid (project
      07B/28/1999) is gratefully acknowledged. 

PMID- 11301456
TI  - Enantioselective Hydrogen Atom Transfer Reactions: Synthesis of N-Acyl-alpha
      Amino Acid Esters This work was supported by the National Institutes of Health
      (NIH-GM-54656). 

PMID- 11301457
TI  - Studies on the Biosynthesis of Paraherquamide: Synthesis and Incorporation of a
      Hexacyclic Indole Derivative as an Advanced Metabolite This work was supported by
      the National Institutes of Health (Grant no. CA70375 to R.M.W.). We wish to
      acknowledge the American Chemical Society Division of Organic Chemistry
      Fellowship (sponsored by SmithKline Beecham) and the Pharmacia-Upjohn Company for
      financial support (to E.M.S.). Mass spectra were obtained on instruments
      supported by the National Institutes of Health Shared Instrumentation Grant (No.
      GM49631). We also wish to thank Professor Dean Crick of the Department of
      Microbiology at Colorado State University for helpful discussions. J.F.S.-C.
      thanks the DGICYT of Spain for a research grant (project no. PB98-1438).

PMID- 11301458
TI  - Novel

PMID- 11301459
TI  - A Seven-Membered Carbon-Ring-Fused Phthalocyanine Analogue in which the pi System
      Changes during Dehydrogenation/Hydrogenation Cycles This research was supported
      by a Grant-in-Aid for Scientific Research (B) No. 11440192, Grant for
      Encouragement of Young Scientists No. 11740368, and Priority Area "Creation of
      Novel Delocalized Electron Systems" Grant No. 12020206 from the Ministry of
      Education, Science, Sports, and Culture, Japan, and the Scandinavia-Japan
      Sasakawa Foundation. 

PMID- 11301460
TI  - A Dense and Efficient Clathrate Hydrate Structure with Unusual Cages NRCC no:
      43877.

PMID- 11301461
TI  - The Oxidative Power of Protonated Hydrogen Peroxide The work was supported by NFR
      (The Norwegian Research Council). The authors thank Drs. Gustav Bojesen and Steen
      Hammerum (University of Copenhagen) for generous cooperation, and Prof. H.
      Bernhard Schlegel (Wayne State University) for computer time and the use of a
      development version of Gaussian 98. Helpful suggestions from Profs. Terry B.
      McMahon (Waterloo University) and Michael T. Bowers (UC, Santa Barbara) are
      acknowledged. 

PMID- 11301462
TI  - Anatomical variations of the extrahepatic biliary tree: review of the world
      literature.
AB  - The anatomy facing a surgeon during cholecystectomy involves complex
      relationships between the hepatic artery, extrahepatic biliary tree, and
      gallbladder. A sound knowledge of the normal anatomy of the extrahepatic biliary
      tract is thus essential in the prevention of operative injury to it. Equally
      important, however, is an understanding of congenital variation of biliary and
      vascular anatomy, as the literature abounds with reports of specific anatomical
      variations, and their operative implications. This article reviews the world
      literature on congenital variation of extrahepatic biliary anatomy.

PMID- 11301463
TI  - Phrenic paresis--a possible additional spinal cord dysfunction induced by neck
      manipulation in cervical spondylotic myelopathy (CSM): a report of two cases with
      anatomical and clinical considerations.
AB  - The clinical records of two male subjects with severe cervical spondylotic
      myelopathy (CSM) who developed respiratory insufficiency after the cervical
      manipulation involved in preoperative anesthetic intubation were examined. Their
      cervical imaging was analyzed with respect to the known anatomic relationships of
      the spinal phrenic nerve nuclei to the spondylotic compressive lesions in an
      attempt to provide the anatomic and pathologic rationales that may explain this
      phrenic paresis as a possible traumatic complication of severe CSM. Perusal of
      extant literature revealed extensive descriptions of CSM symptoms, but none had
      previously reported an associated neuromuscular weakness of the diaphragm.
      Magnetic resonance imaging analyses indicated that the existing degree of upper
      cervical cord compression, when reinforced by the additional posterior and
      anterior pressures consequent to cervical spinal extension and flexion, could
      readily account for the functional impairment of phrenic nerve neuron cells
      and/or their efferent fibers. Thus, the anatomic relations of the phrenic nerve
      nuclear columns and their efferent tracts predispose them to interference by
      compressive lesions found in CSM, and undue manipulation of the cervical spine
      when advanced stenosis is known to be present should be recognized as a possible
      cause of cervical spondylotic myelopathic-phrenic paresis.

PMID- 11301464
TI  - Pretarsal fat compartment in the lower eyelid.
AB  - It is generally accepted that there are three infraorbital fat regions in the
      lower eyelid; medial, central, and lateral compartments. However, removing only
      the fat in the lateral compartment does not remove the bulge just below the
      eyelashes, which is caused by another fat pad. The aim of this study was to
      describe the anatomy of the pretarsal fat compartment and to demonstrate its
      clinical implications in lower lid blepharoplasty. Ten cadavers (total 20 lower
      eyelids) were studied. A skin-muscle flap was reflected to expose the soft
      pretarsal structures. A small stab incision was made on the lateral portion of
      the sac containing fat on the tarsus. Methylene blue dye was injected into the
      sac. Specimens were fixed and sagittal sections in four different planes were
      prepared for histological analysis. The injected dye remained within the sac and
      demarcated it as a pear or cone shaped structure. This encapsulated fat
      compartment sits on the lateral half of the tarsal plate above the lateral
      compartment fat. Auxillary or submuscular fat is well known. This study, however,
      designates the pretarsal fat as "encapsulated" in a compartment instead of being
      unbound. We have named it the "pretarsal fat compartment." Histologically,
      orbital septal fibers separate "pretarsal fat" from lateral infraorbital fat. It
      is recommended that fat in the pretarsal fat compartment be removed during lower
      lid blepharoplasty in order to alleviate the bulge or knoll of the skin just
      below the lower eyelashes.

PMID- 11301465
TI  - Compartment syndrome of the foot.
AB  - The hindfoot compartment syndrome occurs in 10% of cases after calcaneal
      fracture. We analyzed the pathological anatomical reasons for this syndrome using
      the 10 feet from cadavers plastinated and cut into 4-mm thick sequential
      sections. CT scans of patients with calcaneal fractures were then compared with
      the anatomical findings. The key component of this compartment syndrome is the
      quadratus plantae muscle. The sustentacular calcaneal fragment causes bleeding
      from the bone or the medial calcaneal arteries into this compartment. The medial
      and lateral plantar nerves and vessels are then compressed between the quadratus
      plantae muscle and the short flexor digitorum muscle. Relieving pressure by
      surgical decompression of the quadratus plantae compartment via a medial or
      plantar approach is the recommended treatment.

PMID- 11301466
TI  - Anatomic and clinical correlations of the lenticulostriate arteries.
AB  - The authors examined the lenticulostriate (perforating) arteries in the vascular
      casts of 48 middle cerebral arteries (MCA), as well as in the MRI or CT scans of
      32 patients with cerebral infarcts in the MCA territory. The lenticulostriate
      arteries ranged between two and 12 in number, and from 80 microm to 1,400 microm
      in size. They originated from the main trunk, terminal trunks, bifurcation site,
      and/or leptomeningeal branches of the MCA, either separately or from common
      trunks (70.8%). The extreme variations of the supplying region of the perforators
      were noted in seven anatomic specimens. In addition to the basal ganglia, the
      genu, and the anterior limb of the internal capsule, the lenticulostriate
      arteries seemed to supply only the rostral portion of the superior part of the
      posterior limb of the capsule. The patients presented with occlusion of all the
      lenticulostriate arteries, individual arteries, or only their twigs. Complete
      occlusion of these arteries resulted in a huge central hemispheric infarct.
      Occlusion of an individual artery most often caused a large ganglionic-capsular
      infarct. The authors concluded that the lacunar infarcts usually follow occlusion
      of a terminal or a side branch of the lenticulostriate arteries.

PMID- 11301467
TI  - Transverse folds of rectum: anatomic study and clinical implications.
AB  - There are controversies with respect to the location, number, and function of the
      transverse folds of the rectum (TFR), probably because their physioanatomic
      aspects have not been fully investigated. The purpose of this communication was
      to study the anatomic and histologic structure of the TFR aiming at elucidation
      of their function in the light of their structure. The TFR were studied
      morphologically and histologically in 18 cadavers (10 male, 8 female) with a mean
      age of 36.6 +/- 10.4 (SD) years. Barium enema studies were also performed in 36
      volunteers (20 male, 16 female; mean age 38.6 +/- 15.2 [SD] years). The number of
      TFR varied, the commonest findings being two and three. In a few cases, TFR were
      absent or exceeded three in number. Most folds extended beyond the middle of the
      rectal lumen; a few were narrow. They were thick at the base and tapered
      gradually. Microscopically, the TFR contained circular and longitudinal smooth
      muscle fibers; they were rarely purely mucosal. TFR varied in location dividing
      the rectum into compartments; an alternating side-to-side arrangement allows for
      a wavy movement of the stool in the rectum. The wavy movement, compartmental
      division, and the shelving action of the TFR are suggested to retard stool
      movement in the rectum so as to allow time for fecal sampling (stool or gas) and
      for impulses to reach the conscious level to decide whether or not to defecate.
      Further studies are needed to investigate the role of the TFR in clinical
      practice.

PMID- 11301468
TI  - Effects of dexamethasone on tooth eruption in rats: differences in incisor and
      molar eruption.
AB  - A requirement for tooth eruption is the resorption of alveolar bone. Because bone
      resorption is stimulated by dexamethasone both in vivo and in vitro,
      dexamethasone 21-phosphate, a soluble form of dexamethasone, was injected into
      rats to determine its effect on tooth eruption. Such dexamethasone injections
      accelerate the time of intra-osseous eruption in rat incisors but do not
      accelerate the eruption time of rat molars when injected into rats. The
      injections of dexamethasone 21-phosphate also accelerate the time of eyelid
      opening in the postnatal rats, as well as retarding growth, as measured by body
      weight. These effects of dexamethasone 21-phosphate parallel the effects of
      epidermal growth factor injections, including the absence of an effect on molar
      eruption. This suggests that the molecular signals for the initiation of tooth
      eruption (i.e., onset of bone resorption) differ between rat incisors and molars.
      Given that rat incisors are teeth of continuous eruption whereas rat molars are
      teeth of limited eruption, as are human teeth, care must be taken in
      extrapolating results derived from rat incisors to human dentition. In vitro,
      dexamethasone has no effect on the gene expression of either osteoprotegerin or
      epidermal growth factor in dental follicle cells derived from molars. Because
      osteoprotegerin expression during normal tooth eruption is transitorily inhibited
      early postnatally in the molar dental follicle to allow osteoclast formation, the
      absence of inhibition of its expression by dexamethasone could explain why
      dexamethasone does not accelerate eruption in molars.

PMID- 11301469
TI  - William Hunter's casts of the gravid uterus at the University of Glasgow.
AB  - The Hunterian Collection at the University of Glasgow possesses 11 plaster casts
      showing the pregnant uterus. Three correspond to Plates I, IV, and VI of Hunter's
      The Anatomy of the Gravid Uterus Exhibited in Figures (1774), progressive stages
      of dissection of the same specimen. A further three casts show consecutive stages
      of dissection of a uterus containing a fetus presenting by the breech. The other
      specimens show a normal pregnancy at about 6 months, a normal full-term uterus
      with the fetal head becoming engaged, a breech presentation with placenta previa
      and the umbilical cord around the fetal neck, and an obstructed labor with
      distended bladder and colon. The 10 on display show realistic coloring and are
      mounted on black wooden stands. An 11th specimen, amateurishly painted, is not on
      display. The casts differ in their style; some show only the abdomen, pelvis,
      perineum, and thighs, others show the full torso. They also differ in the amount
      of detail shown. The first three casts show the cut femur and muscles at the
      transected ends of the thighs, also shown in some of the plates in the Gravid
      Uterus. Although these features enhance the artistic impact of both the
      engravings and the casts, the authors are unconvinced that Hunter deliberately
      used them to achieve this, as has been claimed.

PMID- 11301470
TI  - Problem in diagnostic imaging: Mediastinal venous anomalies.
AB  - This article presents as a diagnostic problem a rare mediastinal venous anomaly
      detected in a patient with a primary intrathoracic tumor. Its appearance on
      computed tomography (CT) is discussed and compared with that of other
      developmental mediastinal venous anomalies. The individual CT characteristics of
      these anomalies and their clinical significance with respect to the management of
      patients with cancer are also reviewed.

PMID- 11301471
TI  - Dissection: a positive experience.
AB  - First-year medical students were surveyed by questionnaire to assess levels of
      stress and physical symptoms resulting from their experience of the anatomy room.
      There was a 100% response rate from the 188 students. Most students (95%) found
      the prospect of their first visit to the anatomy room exciting. A small number
      initially experienced physical symptoms, but these had improved significantly 10
      weeks later. Most students suffered very little or no stress (80%) on their first
      visit with only 2% of respondents rating their stress levels as high. Ten weeks
      later, 87% experienced little or no stress with only 1% stating that they had
      high stress levels. The anatomy room was rated to be less stressful than workload
      and assessments. Students reported that the anatomy room provoked thoughts of
      mortality, and 27% suggested that there should be more preparation before the
      first visit to the anatomy room. Our findings support previous studies suggesting
      that American/Canadian students in particular find anatomy stressful. However,
      the wisdom of interpreting adverse reactions as symptomatic of post-traumatic
      stress disorder is questioned. This study shows the anatomy room to be a positive
      learning experience for the students of the Royal College of Surgeons in Ireland.

PMID- 11301472
TI  - Student responses to the gross anatomy laboratory in a medical curriculum.
AB  - Working with cadavers, whether through active dissection or by examination of
      prosected specimens, constitutes a potential stressor in medical education
      although there is no consensus on its effect. Some reports have suggested that it
      creates such a strongly negative experience that it warrants special curricular
      attention. To assess the issue for ourselves, we administered surveys to the
      freshman medical students taking the Anatomical Sciences course in the problem
      based Alternative Curriculum (A.C.) at Rush Medical College for four consecutive
      years. We found that although a vast majority of students expressed a positive
      attitude toward the experience, both before and after taking the course, there
      remains a small percentage of students for whom human dissection may initially be
      a traumatic experience. We offer explanations for our findings, comments on
      disparate results from other studies and suggestions for appropriate responses by
      anatomy faculty, who must address these student needs.

PMID- 11301473
TI  - Commentary: is the concept of "tumor promotion" a useful paradigm?
AB  - Since the demonstration of the multistage nature of carcinogenesis in
      experimental work on mouse skin carcinogenesis (and subsequently on various other
      organ systems in other organisms), the concepts of "initiation", "promotion", and
      "progression" were operationally generated from empiric data. Because these early
      observations and concepts had no mechanistic explanations, various hypotheses
      have been generated to explain the unique characteristics of each phase (e.g.,
      initiation, being irreversible, was ascribed as the result of DNA damage leading
      to mutagenesis; promotion, being interruptible or reversible, was believed to be
      caused by epigenetic mechanisms; progression, also being irreversible, was
      believed to be caused by genetic instability that led to mutagenic and epigenetic
      changes). In addition, many of the molecular, biochemical, and cellular
      experiments designed to investigate the mechanistic bases of these phases used
      technologies that did not always lead to unequivocal interpretations, and because
      "real-life" carcinogenesis does not mimic controlled experimental conditions of
      the initiation/promotion/progression experiments, many investigators believe that
      these concepts have lost their usefulness. In this commentary, I explain some of
      the confusion concerning the concept of promotion and suggest that, by
      understanding the limitations of many in vitro assays used to characterize
      mutagens, by integrating other theories of carcinogenesis (i.e., stem cell
      theory), and by recognizing the role of epigenetic agents, specifically,
      modulated gap-junctional intercellular communication, the concept of promotion
      can provide valuable insights into the carcinogenic process. Mol. Carcinog.
      30:131--137, 2001.

PMID- 11301474
TI  - Sequential changes in hepatocarcinogenesis induced by diethylnitrosamine plus
      thioacetamide in Fischer 344 rats: induction of gankyrin expression in liver
      fibrosis, pRB degradation in cirrhosis, and methylation of p16(INK4A) exon 1 in
      hepatocellular carcinoma.
AB  - To clarify the sequential changes in pRB and p16 during different stages of
      hepatocarcinogenesis such as fibrosis, cirrhosis, hepatocellular adenoma (HCA),
      and hepatocellular carcinoma (HCC), male Fischer 344 rats were singly injected
      with diethylnitrosamine (DEN), immediately followed with phenobarbital for 1 wk
      and then thioacetamide (TAA) for 39 wk in drinking water. Rats were killed at 9,
      20, 30, and 40 wk after DEN initiation and changes of pRB level, p16 gene
      hypermethylation, and in vivo gankyrin expression were examined. Histologic
      examination showed stepwise appearances of fibrosis, cirrhosis, HCA, and HCC at
      weeks 9, 20, 30, and 40, respectively. Hypermethylation of p16 exon 1 was not
      found until HCA but appeared in 50% of the rats with HCC accompanied by complete
      loss of its mRNA expression. The amount of glutathione S-transferase--gankyrin
      bound to pRB and pRB degradation in the liver depended on the concentration of
      gankyrin and incubation time. Gankyrin expression preceded pRB degradation in
      liver cirrhosis. In conclusion, gankyrin expression induced in liver fibrosis
      accelerated the degradation of pRB during liver cirrhosis, and inactivation of
      p16 exon 1 by DNA hypermethylation occurred during the progression of tumor cells
      to poorly differentiated HCC. Inactivation of pRB and/or p16 resulted in complete
      loss of regulation in the cell-division cycle during early and late stages,
      respectively, of hepatocarcinogenesis. Mol. Carcinog. 30:138--150, 2001.

PMID- 11301475
TI  - Two consistently deleted regions within chromosome 1p32-pter in human non-small
      cell lung cancer.
AB  - Allelic losses at 1p32-pter have been reported as frequent events in human non
      small cell lung cancer (NSCLC). To further characterize the region of deletions,
      we studied loss of heterozygosity on a panel of 102 microdissected NSCLC samples
      with 20 polymorphic markers spanning 1p32-pter. Two shortest regions of the
      overlap of the deletions (SROs) were found: SRO 2a (D1S417--D1S57) and SRO 2b
      (D1S450--D1S243). Allelic losses at either region correlated independently with
      advanced stage of disease and with postoperative metastasis and relapse (P <
      0.05), suggesting that crucial genes in these regions are involved in NSCLC
      progression. Mol. Carcinog. 30:151--158, 2001.

PMID- 11301476
TI  - Chromosome 3p tumor-suppressor gene alterations in cervical carcinomas.
AB  - Loss of heterozygosity (LOH) on chromosome 3p is a common event in cervical
      cancer and typically occurs in a dispersed pattern involving several loci. This
      implies that more than one resident tumor-suppressor gene is involved in the
      genesis of these tumors; however, specific targets remain to be identified. The
      region of 3p14.2-pter encompasses a region of frequent loss and contains at least
      three tumor-suppressor genes: fragile histidine triad (FHIT), transforming growth
      factor-beta receptor II (T beta R-II), and Von Hippel-Lindau. To identify those
      loci within 3p14.2-pter that are important in cervical cancer, invasive tumors
      were first subjected to high-density LOH analysis. With 25 microsatellite
      markers, LOH was detected in seven of 15 cervical carcinomas (47%). Losses always
      included markers mapping to 3p22, and markers at this location were exclusively
      lost in two tumors, implicating this as a site of a cervical tumor-suppressor
      gene. Because it is a known tumor-suppressor gene located at 3p22 and thus a
      potential target for inactivation in these tumors, the T beta R-II gene was
      subsequently screened for mutation and altered expression levels. Whereas no
      tumor-derived mutations were detected in any of the tumors, six of ten tumors
      showed T beta R-II transcript levels reduced by > or = 50% when compared with
      normal cervical epithelium. Nine of 15 (60%) tumors exhibited LOH at 3p22 or
      reduced expression of T beta R-II, suggesting that reduced T beta R-II levels
      contribute to cervical tumorigenesis. Two cases exhibited silent germline
      polymorphisms of T beta R-II: one corresponding to a C1167T transversion and the
      other to an A1266G transition. The FHIT gene, which is located at 3p14.2, also
      frequently incurred LOH and abnormal transcription in these tumors. LOH of FHIT
      was observed in five of the 15 tumors analyzed. Neither mutations nor homozygous
      deletions of FHIT were detected in the tumors. However, aberrantly short
      transcripts of the FHIT gene were evident in six of nine (67%) tumors. Only one
      of these also displayed LOH, indicating that this gene was altered in at least 10
      of 15 (67%) tumors. These results provide evidence that the inactivation of two
      known tumor-suppressor genes, TbetaR-II and FHIT, on chromosome 3p is involved in
      cervical carcinogenesis. Mol. Carcinog. 30:159--168, 2001.

PMID- 11301477
TI  - Correlation of p27 protein expression with HER-2/neu expression in breast cancer.
AB  - Strong expression of human epidermal growth factor receptor 2 (HER-2)/neu in
      breast cancer has been associated with poor prognosis. Reduced expression of
      p27(Kip1), a cyclin-dependent kinase inhibitor, correlates with poor clinical
      outcome in breast cancer. In this study, we provide a correlation between these
      two important prognostic markers in patients with breast cancer. Breast tumor
      screening using immunohistochemistry indicated that downregulation of p27
      correlated with HER-2/neu overexpression in studying 11 normal breast tissues and
      51 primary breast carcinomas. We found HER-2/neu protein overexpression in 20
      (41%) of 49 breast cancers and low p27 protein expression in 47 (92%) of 51
      breast cancers. All 20 (100%) of the tumors that overexpressed HER-2/neu had low
      levels of p27 protein product; this correlation was statistically significant (P
      = 0.035). Decreasing p27 expression correlated with increasing HER-2/neu
      activity. Our results suggest that one function of the HER-2/neu product is to
      downregulate p27 expression in breast cancer. This study may be significant in
      selecting patients for HER-2/neu antibody therapy in the future. Mol. Carcinog.
      30:169--175, 2001.

PMID- 11301478
TI  - Induction of a bystander effect in HeLa cells by using a bigenic vector carrying
      viral thymidine kinase and connexin32 genes.
AB  - We previously showed that gap junction intercellular communication mediates the
      bystander effect in anticancer gene therapy with the herpes simplex virus
      thymidine kinase (HSV-tk) and ganciclovir. Because most cancer cell lines have
      lost their ability to communicate through gap junctions, we investigated whether
      we could induce such a communication by transferring a gene for a gap junction.
      We transfected a vector carrying the HSV-tk (tk) and gap junction (connexin (Cx)
      32) genes (Cx32(+)tk(+)) into noncommunicating HeLa cells. We compared the
      cytotoxicity of ganciclovir with mixtures of these cells and HeLa cells that
      expressed (Cx32(+)) or did not express (Cx32(-)) the Cx32 gene. The bystander
      effect was strong when the two mixed cell types expressed Cx32 (i.e.,
      Cx32(+)tk(+) cells and Cx32(+)tk(-) cells). Only 25% of cells survived in this
      communicating mixture, even when only 10% of the cells were Cx32(+)tk(+). There
      was also a moderate bystander effect when the Cx32(+)tk(+) cells were mixed with
      noncommunicating HeLa cells in a 50% ratio. These results demonstrated that the
      bystander effect is enhanced by Cx32 and suggested that expression of Cx in only
      one cell type in a mixture can cause a bystander effect. Mol. Carcinog. 30:176-
      180, 2001.

PMID- 11301479
TI  - Interaction of a designed interleukin-10 epitope mimic with an antibody studied
      by isothermal titration microcalorimetry.
AB  - The mechanism of recognition of proteins and peptides by antibodies and the
      factors determining binding affinity and specificity are mediated by essentially
      the same features. However, additional effects of the usually unfolded and
      flexible solution structure of peptide ligands have to be considered. In an
      earlier study we designed and optimized six peptides (pepI to pepVI) mimicking
      the discontinuous binding site of interleukin-10 for the anti-interleukin-10
      monoclonal antibody (mab) CB/RS/1. Three of them were selected for analysis of
      their solution conformation by circular dichroism measurements. The peptides
      differ in the content of alpha-helices and in the inducibility of helical
      secondary structures by trifluoroethanol. These properties, however, do not
      correlate with the binding affinity. PepVI, a 32-mer cyclic epitope mimic, has
      the highest affinity to mab CB/RS/1 identified to date. CD difference
      spectroscopy suggests an increase of the alpha-helix content of pepVI with
      complex formation. Binding of pepVI to mab CB/RS/1 is characterized by a large
      negative, favorable binding enthalpy and a smaller unfavorable loss of entropy
      (DeltaH degrees = -16.4 kcal x mol(-1), TDeltaS degrees = -6.9 kcal x mol(-1))
      resulting in DeltaG degrees = -9.5 kcal x mol(-1) at 25 degrees C as determined
      by isothermal titration calorimetry. Binding of pepVI is enthalpically driven
      over the entire temperature range studied (10-35 degrees C). Complex formation is
      not accompanied by proton uptake or release. A negative heat capacity change
      DeltaC(p) of -0.354 kcal x mol(-1) x K(-1) was determined from the temperature
      dependence of DeltaH degrees. The selection of protein mimics with the observed
      thermodynamic properties is promoted by the applied identification and iterative
      optimization procedure.

PMID- 11301480
TI  - Functional characterization of two anti-estradiol antibodies as deduced from
      modelling and site-directed mutagenesis experiments.
AB  - Monoclonal antibodies are now widely used to measure the concentration of steroid
      hormones in human serum samples. The great development of molecular engineering
      techniques over the past 10 years has made possible the improvement of
      specificity and/or sensitivity of selected antibodies. We have obtained two
      monoclonal antibodies, 17E12E5 and 10G6D6, using estradiol-6-ethyl methoxy
      carbonyl (EMC)-bovine serum albumin (BSA) as immunogen. To tentatively improve
      their affinities for natural estradiol, we have initiated their structural and
      functional studies. For this purpose, we have cloned and sequenced the genes
      encoding the variable fragments of each antibody. Single chain variable fragments
      (scFv) were produced into the periplasmic space of E. coli using the pLIP6
      expression vector. Mapping of the functional structures of both antibodies was
      obtained by combination of modelling and mutational analyses together with cross
      reaction studies. The two binding pockets are described and models of estradiol
      complexed to 17E12E5 and 10G6D6 are proposed.

PMID- 11301481
TI  - Exquisite specificity and peptide epitope recognition promiscuity, properties
      shared by antibodies from sharks to humans.
AB  - This review considers definitions of the specificity of antibodies including the
      development of recent concepts of recognition polyspecificity and epitope
      promiscuity. Using sets of homologous and unrelated peptides derived from the
      sequences of immunoglobulin and T cell receptor chains we offer operational
      definitions of cross-reactivity by investigating correlations of either
      identities in amino acid sequence, or in hydrophobicity/hydrophilicity profiles
      with degree of binding in enzyme-linked immunosorbent assays. Polyreactivity, or
      polyspecificity, are terms used to denote binding of a monoclonal antibody or
      purified antibody preparation to large complex molecules that are structurally
      unrelated, such as thyroglobulin and DNA. As a first approximation, there is a
      linear correlation between degree of sequence identity or
      hydrophobicity/hydrophilicity and antigenic cross-binding. However, catastrophic
      interchanges of amino acids can occur where changing of one amino acid out of 16
      in a synthetic peptide essentially eliminates binding to certain antibodies. An
      operational definition of epitope promiscuity for peptides is the case where two
      peptides show little or no identity in amino acid sequence but bind strongly to
      the same antibody as shown by either direct binding or competitive inhibition.
      Analysis of antibodies of humans and sharks, the two most divergent species in
      evolution to express antibodies and the combinatorial immune response, indicates
      that the capacity for both exquisite specificity and epitope recognition
      promiscuity are essential conserved features of individual vertebrate antibodies.

PMID- 11301482
TI  - Evidence for a DNA triplex in a recombination-like motif: I. Recognition of
      Watson-Crick base pairs by natural bases in a high-stability triplex.
AB  - Data are presented on a triplex type with two parallel homologous strands for
      which triplex formation is almost as strong as duplex formation at least for some
      sequences and even at pH 7 and 0.2 M NaCl. The evidence mainly rests upon
      comparing thermodynamic properties of similar systems. A paperclip
      oligonucleotide d(A12C4T12C4A12) with two linkers C4 obviously can form a triplex
      with parallel back-folded adenine strand regions, because the single melting
      transition of this complex splits in two transitions by introducing mismatches
      only in the third strand region. Respectively, a hairpin duplex d(A12C4T12) and a
      single strand d(A12) form a triplex as a 1:1 complex in which the second adenine
      strand is parallel oriented to the homologous one in the Watson-Crick paired
      duplex. In this system the melting temperature T(m) of the triplex is practically
      the same as that of the duplex d(A12)-d(T12), at least within a complex
      concentration range of 0.2-4.0 microM. The melting behaviour of complexes between
      triplex stabilizing ligand BePI and the system hairpin duplex plus single strand
      supports the triplex model. Non-denaturing gel electrophoresis suggests the
      existence of a triplex for a system in which five of the twelve A-T*A base triads
      are substituted by C-G*C base triads. The recognition between any substituted
      Watson-Crick base pair (X-Y) in the hairpin duplex d(A4XA7C4T7YT4) and the
      correspondingly replaced base (Z) in the third strand d(A4ZA7) is mutually
      selective. All triplexes with matching base substitutions (Z = X) have nearly the
      same stability (T(m) values from 29 to 33.5 degrees C), whereas triplexes with
      non-matching substitutions (Z not equal X) show a clearly reduced stability (T(m)
      values from 15 to 22 degrees C) at 2microM equimolar oligonucleotide
      concentration. Most nucleic acid triple helices hitherto known are limited to
      homopurine-homopyrimidine sequences in the target duplex. A stable triplex
      formation is demonstrated for inhomogeneous sequences tolerating at least 50%
      pyrimidine content in the homologous strands. On the basis of the surprisingly
      similar thermodynamic parameters for duplex and triplex, and of the fact that
      this triplex type seems to be more stable than many other natural DNA triplexes
      known, and on the basis of semiempirical and molecule mechanical calculations, we
      postulate bridging interactions of the third strand with the two other strands in
      the triplex according to the recombination motif. This triplex, denoted by us
      'recombination-like form', tolerates heterogeneous base sequences.

PMID- 11301485
TI  - Nerve fibers innervating the cranial and spinal meninges: morphology of nerve
      fiber terminals and their structural integration.
AB  - Pachymeninx and leptomeninx of cranial cavity and spine are considerably
      different in their collagenous fiber texture, cellular composition,
      vascularization, and innervation. The majority of meningeal nerve fibers
      terminate as free nerve endings whereas encapsulated and lamellated nerve
      terminals additionally occur in higher vertebrates including man. With respect to
      nerve fiber classification, arborization pattern, topography, and organization of
      the microenvironment at the termination site afferent and efferent nerve
      terminals are differentiated. Only the dura mater and the pial subcompartment of
      the leptomeninx possess the morphological prerequisites for neurogenic
      inflammation. In the current review, the results of morphological studies
      regarding the meningeal innervation including the sites of CSF (cerebrospinal
      fluid) production and absorption are discussed with emphasis on their structure
      function relationships.

PMID- 11301486
TI  - Innervation of cerebral blood vessels: morphology, plasticity, age-related, and
      Alzheimer's disease-related neurodegeneration.
AB  - The light microscopical and ultrastructural morphology of the innervation of the
      major cerebral arteries and pial vessels is described, including the origins of
      the different groups of nerve fibres and their characteristic neurotransmitter
      phenotype. Species and region specific variations are described and novel data
      regarding the parasympathetic innervation of cerebral vessels are presented. The
      dynamic nature, or plasticity, of cerebrovascular innervation is emphasized in
      describing changes affecting particular subpopulations of neurons during normal
      ageing and in Alzheimer's disease. The molecular controls on plasticity are
      discussed with particular reference to target-associated factors such as the
      neurotrophins and their neuronal receptors, as well as extracellular matrix
      related factors such as laminin. Hypotheses are presented regarding the principal
      extrinsic and intrinsic influences on plasticity of the cerebrovascular
      innervation.

PMID- 11301487
TI  - Cholinergic-nitrergic transmitter mechanisms in the cerebral circulation.
AB  - Cerebral blood vessels from several species are innervated by vasodilator nerves.
      Acetylcholine (ACh) released from parasympathetic cholinergic nerves was first
      suggested to be the transmitter for vasodilation. Results from pharmacological
      studies in isolated cerebral arterial ring preparations, however, have
      demonstrated that nitric oxide (NO) but not ACh mediates the major component of
      neurogenic vasodilation. More recently, ACh and NO have been shown to co-release
      from the same cholinergic-nitrergic nerves, and that ACh acts as a presynaptic
      transmitter in modulating NO release. In this communication, evidence for the
      neuronal origin of NO and possible role of ACh in modulating NO release in large
      cerebral arteries at the base of the brain will be discussed.

PMID- 11301488
TI  - Meningeal nociception: electrophysiological studies related to headache and
      referred pain.
AB  - Headaches, which are usually referred to characteristic sites of the skull, are
      believed to involve meningeal nociceptors located in the dura mater encephali.
      Animal experiments show that these meningeal nociceptors are polymodal and
      usually highly sensitive to mechanical stimulation. These properties are also
      characteristic for the second order neurons in the spinal trigeminal nucleus,
      most of which receive convergent input from facial receptive sites. Sensitization
      of primary and secondary neurons by chemical irritants to mechanical stimuli may
      be an important mechanism in the generation of headaches. The convergent input
      from extracranial structures, which seems to be differentially organized in
      rodents and man, may explain the typical features of referred headache. Targets
      for analgesics used in the therapy of headaches (non-steroidal antiinflammatory
      drugs, 5-HT(1) receptor agonists) are probably meningeal nociceptors and
      different sites of the central trigeminal nociceptive and antinociceptive
      pathways.

PMID- 11301489
TI  - Physiology of meningeal innervation: aspects and consequences of chemosensitivity
      of meningeal nociceptors.
AB  - Up to now, the cause of most types of headaches is unknown. Why headache starts
      or why it fades away during hours or a few days is still a mystery. This
      phenomenon makes headache unique compared to other pain states. For long it has
      been known that during headache sensory structures in the meninges are activated.
      But it was not until the last two decades that scientists investigated the
      physiology of the sensory innervation of the meninges. Animal models and in vitro
      preparations have been developed to get access to the meninges and to determine
      the response properties of meningeal afferents. Although animals hardly can tell
      their pain, blood pressure measurements and observations of behaviour in two
      models of headache suggest that such animal models are valid and may add
      remarkable information to our understanding of human headache. Since chemicals
      and endogenous inflammatory mediators may alter sensory thresholds and
      responsiveness of neurons, they are putative key molecules in triggering
      pathophysiological sensory processing. This review briefly summarizes what is
      known about the chemosensitivity of meningeal innervation.

PMID- 11301490
TI  - Elemental maps from EFTEM images using two different background subtraction
      models.
AB  - Acquisition of a great number of energy-filtered images in a TEM (EFTEM) around
      the characteristic signal with a low energy-selecting slit allows display of the
      electron energy loss (EEL)-spectrum of regions of interest (ROIs) of a sample.
      These EEL-spectra can be submitted to the different treatments already in use for
      electron energy loss spectroscopy (EELS). In particular, it is possible to fit
      the experimental background with different mathematical models, using images
      acquired below and above a characteristic ionization edge. After this fitting,
      elemental maps can be computed by subtraction of the extrapolated/interpolated
      background from the characteristic images. In this work, we compared two
      mathematical models for background fitting-the Egerton power law and the log
      polynomial law. We studied the low-energy region (40-150 eV) and a higher-energy
      region (350-600 eV) with the aid of software for interactive processing of EFTEM
      image series that we developed. The analyzed elements were the constitutive
      elements: iron, phosphorus, nitrogen, and oxygen in several biological materials.
      Two analytical TEMs, one equipped with a post-column and the other with an in
      column spectrometer, were used. Our experimental results confirm that the power
      law is very sensitive to the value of the energy loss of the pre-edge images when
      the background is computed by extrapolation. The log-polynomial model is less
      sensitive than the power law model to the value of the energy loss of the pre
      edge images in the low energy region. For the oxygen K edge at 535 eV, it gives
      the best fit when it is combined with the interpolation method. The use of
      programs that facilitate the handling of EFTEM image series, and the controlled
      calculation of the background under the characteristic images, represent a step
      forward in the generation of elemental maps.

PMID- 11301491
TI  - Theoretical versus experimental resolution in optical microscopy.
AB  - The aim of this article is to compare experimental resolution under different
      conditions with theoretical resolution predicted using electromagnetic
      diffraction theory. Imaging properties of fluorescent beads of three different
      diameters (0.1 microm, 0.2 microm, and 0.5 microm) as well as imaging properties
      of four different fluorescence-stained DNA targets (ABL gene, BCR gene,
      centromere 6, and centromere 17) are studied. It is shown how the dependence of
      the resolution on object size varies with wavelength (520 nm versus 580 nm), type
      of microscopy (wide-field, confocal using Nipkow disk, confocal laser scanning)
      and basic image processing steps (median and gaussian filters). Furthermore,
      specimen influence on the resolution was studied (the influence of embedding
      medium, coverglass thickness, and depth below the coverglass). Both lateral and
      axial resolutions are presented. The results clearly show that real objects are
      far from being points and that experimental resolution is often much worse than
      the theoretical one. Although the article concentrates on fluorescence imaging
      using high NA objectives, similar dependence can also be expected for other
      optical arrangements.

PMID- 11301492
TI  - Neurogenic inflammation in the context of migraine.
AB  - Despite considerable research into the pathogenesis of idiopathic headaches, such
      as migraine, the pathophysiological mechanisms underlying them remain poorly
      understood. Although it is well established that the trigeminal nerve becomes
      activated during migraine, the consequences of this activation remain
      controversial. One theory, based on preclinical observations, is that activation
      of trigeminal sensory fibers leads to a painful neurogenic inflammation within
      the meningeal (dural) vasculature mediated by neuropeptide release from
      trigeminal sensory fibres and characterized by plasma protein extravasation,
      vasodilation, and mast cell degranulation. Effective antimigraine agents such as
      ergots, triptans, opioids, and valproate inhibit preclinical neurogenic dural
      extravasation, suggesting that this activity may be a predictor of potential
      clinical efficacy of novel agents. However, several clinical trials with other
      agents that inhibit this process preclinically have failed to show efficacy in
      the acute treatment of migraine in man. Alternatively, it has been proposed that
      painful neurogenic vasodilation of meningeal blood vessels could be a key
      component of the inflammatory process during migraine headache. This view is
      supported by the observation that jugular plasma levels of the potent
      vasodilator, calcitonin gene-related peptide (CGRP) are elevated during the
      headache and normalized by successful sumatriptan treatment. Preclinically,
      activation of trigeminal sensory fibers evokes a CGRP-mediated neurogenic dural
      vasodilation, which is blocked by dihydroergotamine, triptans, and opioids but
      unaffected by NK1 receptor antagonists that failed in clinical trials. These
      observations suggest that CGRP release with associated neurogenic dural
      vasodilation may be important in the generation of migraine pain, a theory that
      would ultimately be tested by the clinical testing of a CGRP receptor antagonist.

PMID- 11301493
TI  - Neuroimaging in headache.
AB  - Neuroimaging of primary headache syndromes, such as cluster headache and
      migraine, has begun to provide a glimpse of the neuroanatomical and physiological
      basis of the conditions. Although these headache types have been widely described
      as vascular, there is now considerable imaging and clinical evidence to suggest
      that they are primarily driven from the brain. The shared anatomical and
      physiological substrate for both of these clinical problems is the neural
      innervation of the cranial circulation. Functional imaging with positron emission
      tomography (PET) has shed light on the genesis of both syndromes, documenting
      activation in the midbrain and pons in migraine, and in the hypothalamic grey in
      cluster headache. These areas are involved not simply as a response to first
      division nociceptive pain impulses but specifically in each syndrome, probably in
      some permissive or dysfunctional role. In a recent PET study in cluster headache,
      as well as brain activation, tracer pooled in the region of the major basal
      arteries. This is likely to be due to vasodilatation of these vessels during the
      acute pain-attack and represents the first convincing activation of neural
      vasodilator mechanisms in humans. The author takes the view that the known
      physiology and pathophysiology of the systems involved dictate that these
      disorders should be collectively regarded as neurovascular headaches to place
      emphasis on the interaction between nerves and vessels, which is the underlying
      characteristic of these syndromes. Understanding this neurovascular relationship
      facilitates an understanding of the pain mechanisms, while characterising the CNS
      dysfunction will ultimately allow us to dissect out the basic pathogenesis of
      these disorders.

PMID- 11301494
TI  - The trigeminovascular system in bacterial meningitis.
AB  - Headache as a cardinal symptom of acute meningitis reflects activation of
      trigeminal afferents from the meninges. With their perivascular endings, these
      fibers form the so-called trigeminovascular system (TVS), which releases
      proinflammatory neuropeptides upon nociceptive stimulation. In the present
      article, we review a role of the TVS in enhancing the early inflammatory response
      of bacterial meningitis. Furthermore, we discuss inhibition of neuropeptide
      release from the TVS using 5HT(1B/D) agonists as a potential new anti
      inflammatory treatment strategy for early bacterial meningitis.

PMID- 11301495
TI  - Functional immunohistochemistry of neuropeptides and nitric oxide synthase in the
      nerve fibers of the supratentorial dura mater in an experimental migraine model.
AB  - The supratentorial cerebral dura of the albino rat is equipped with a rich
      sensory innervation both in the connective tissue and around blood vessels, which
      includes nociceptive axons and their terminals; these display intense calcitonin
      gene-related peptide (CGRP) immunoreactivity. Stereotactic electrical stimulation
      of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine
      model, caused marked increase and disintegration of club-like perivascular CGRP
      immunopositive nerve endings in the dura mater and induced an apparent increase
      in the lengths of CGRP-immunoreactive axons. Intravenous administration of
      sumatriptan or eletriptan, prior to electrical stimulation, prevented
      disintegration of perivascular terminals and induced accumulation of CGRP in
      terminal and preterminal portions of peripheral sensory axons. Consequently,
      immunopositive terminals and varicosities increased in size; accumulation of
      axoplasmic organelles resulted in the "hollow" appearence of numerous
      varicosities. Since triptans exert their anti-migraine effect by virtue of
      agonist action on 5-HT(1D/B) receptors, we suggest that these drugs prevent the
      release of CGRP from perivascular nerve terminals in the dura mater by an action
      at 5-HT(1D/B) receptors. Nitroglycerine (NitroPOHL), given subcutaneously to
      rats, induces increased beading of nitric oxide synthase (NOS)-immunoreactive
      nerve fibers in the supratentorial cerebral dura mater, and an apparent increase
      in the number of NOS-immunoreactive nerve fibers in the dural areas supplied by
      the anterior and middle meningeal arteries, and the sinus sagittalis superior.
      Structural alterations of nitroxidergic axons innervating blood vessels of the
      dura mater support the idea that nitric oxide (NO) is involved in the induction
      of headache, a well-known side effect of coronary dilator agents.

PMID- 11301496
TI  - Catecholaminergic and acetylcholine esterase containing nerves of cranial and
      spinal dura mater in humans and rodents.
AB  - The innervation of cranial and spinal dura mater in humans and rodents was
      studied by examining several dural zones (vascular, perivascular, intervascular)
      in different regions. Characterization and distribution of dural
      acetylcholinesterase-positive nerve fibers, catecholaminergic nerve fibers, and
      mast cells are analyzed and discussed. The results of chemical and surgical
      sympathectomy as well as the relationships between catecholaminergic nerve fibers
      and mast cells are studied. Our results are discussed in the light of possible
      implications in the physiopathology of dural algic syndromes including
      cephalalgia and spinal pain.

PMID- 11301497
TI  - Origin and Co-localization of nitric oxide synthase, CGRP, PACAP, and VIP in the
      cerebral circulation of the rat.
AB  - The origin of perivascular nerve fibres storing nitric oxide synthase (NOS) and
      co-localisation with perivascular neuropeptides were examined in the rat middle
      cerebral artery (MCA) by retrograde tracing with True Blue (TB) in combination
      with immunocytochemistry. Application of TB to the proximal part of the middle
      cerebral artery labelled nerve cell bodies ipsilaterally in the trigeminal,
      sphenopalatine, otic, and superior cervical ganglia. A few labelled cell bodies
      were seen contralaterally, suggesting bilateral innervation. In the
      parasympathetic sphenopalatine and otic ganglia, numerous TB-labelled cell bodies
      contained neuronal NOS (C- and N-terminal), vasoactive intestinal peptide (VIP),
      and pituitary adenylate cyclase activating peptide (PACAP). In the trigeminal
      ganglion, almost all TB-labelled cell bodies contained calcitonin gene-related
      peptide (CGRP) but only a few cells contained NOS. In the superior cervical
      ganglion, the majority of the TB-labelled nerve cells contained neuropeptide Y
      (NPY) but none of them contained NOS. Removal of the ipsilateral sphenopalatine
      ganglion caused a slight reduction in the number of perivascular VIP-, PACAP-,
      and NOS-containing fibres after 3 days in the MCA while there was no difference
      at 2 and 4 weeks after the denervation as compared to control. This indicates
      that the parasympathetic VIP-, PACAP-, and NOS-immunoreactive nerve fibres in the
      rat MCA originate from several sources.

PMID- 11301498
TI  - Histological demonstration of increased vascular permeability in the dura mater
      of the rat.
AB  - Neurogenic inflammation of the dura mater encephali has been suggested to play an
      important role in the pathophysiology of headaches. Although functional studies
      using extravasation techniques indicate an enhanced permeability of blood vessels
      after chemical or electrical stimulation of C-fibres supplying the dura mater,
      histological demonstration of leaky blood vessels is still a problem. We used the
      vascular labelling method combined with i.v. injection of colloidal silver
      solution to test the permeability increasing effect of intravenous administration
      of substance P, topical application of mustard oil or acidic phosphate buffer and
      local electrical stimulation of the exposed dura mater. Histological
      characteristics of increased vascular permeability were observed exclusively
      after mustard oil and acidic phosphate buffer. This observation may indicate
      different mechanisms of increased vascular permeability involving pinocytosis and
      formation of interendothelial gaps selectively visualized by the vascular
      labelling method.

PMID- 11301499
TI  - Ultrastructural and permeability features of microvessels in the periventricular
      area of senescence-accelerated mice (SAM).
AB  - Brain transfer of intravenously injected horseradish peroxidase (HRP) and the
      ultrastructural features of the vessels were examined in periventricular areas in
      senescence-accelerated mice (SAMP8), which show age-related deficits in learning
      and memory, and senescence-accelerated resistant mice (SAMR1), which do not show
      age-related deficits. In all mice examined with light microscopy, staining
      reaction for HRP was seen in the periventricular area adjacent to the medial side
      of the lateral ventricle. Electron microscopic examination in the periventricular
      area of young and old mice of both strains showed that the staining reaction for
      HRP appeared in the vesicular profiles of the endothelial cytoplasm, the
      cytoplasm of the perivascular cells, the basal lamina, and the adjoining
      extracellular spaces of the white matter, suggesting an incomplete blood-brain
      barrier (BBB) in the periventricular white matter. In addition, irregularly
      thickened endothelial cell cytoplasm, membranous inclusions within the basal
      lamina, and electron-dense endothelial cell cytoplasm were occasionally seen in
      aged SAMP8 mice. These findings were not observed in 3-month-old SAMP8 mice and 3
      and 13-month-old SAMR1 mice. Perivascular collagen deposits were also frequently
      seen in aged SAMP8 mice. These findings indicate that the endothelial cells and
      pericytes in the periventricular white matter in aged SAMP8 mice have an
      ultrastructure with damaged BBB function. Intravascular substances can easily
      penetrate the periventricular white matter and the BBB of the vessels in the area
      can be deteriorated with aging in SAMP8 mice.

PMID- 11301500
TI  - Cryosectioning distortion reduction using tape support.

PMID- 11301501
TI  - Percutaneous and limited open reduction of intra-articular distal radial
      fractures.
AB  - Fluoroscopy monitors intra-articular distal radial fracture reduction and
      stabilisation. The reduction is guided by traction, ligamentotaxis and
      manipulation, and when necessary, completed by minimally invasive percutaneous or
      limited open instrumentation. Kirschner wires effectively splint the reduction
      until fracture callus is visualised on X-ray. An occasional mini plate is
      required to buttress a displaced volar medial lunate facet (die punch) fragment
      into position. First, major metaphyseal articular fragments are approximated to
      restore the articular surface. Smaller fragments follow their larger counterparts
      into position or may be ignored (the "Rule of the Majority" or "Vassal Rule").
      The repaired metaphysis is then aligned with and stabilised to the diaphysis.
      Cancellous bone may be inserted through small targeted incisions when defects and
      areas of comminution are present. The wrist is splinted in a functional (slightly
      extended) position for three to four weeks in uncomplicated cases. Digital
      elevation and rehabilitation are emphasised during the early stages of fracture
      healing. After callus appears on X-ray, progressive wrist rehabilitation is
      initiated and the patients are weaned from their splints. Minimally invasive
      surgical intervention, good pain control and early rehabilitation maximise
      functional recovery and minimise morbidity, medical costs and lost work time.

PMID- 11301502
TI  - The arthroscopic management of intra-articular distal radius fractures.
AB  - Intra-operative arthroscopy and fluoroscopy provide improved visualisation and
      guide the restoration of intra-articular distal radial fractures while minimising
      the operative dissection required for their stabilisation. Radial styloid
      fractures, distal radial fractures with dorsal, palmar or combined ulnar-sided
      "die punch" fragments, palmar and dorsal Barton's fractures, and various three-
      and four-part intra-articular fractures without significant bone loss or defect
      are especially suited for this technique. The experienced arthroscopist may wish
      to apply the technique to more severely comminuted intra-articular fractures.
      Bone defects may be approached through a limited dorsal incision traversing the
      3rd dorsal wrist compartment. Arthroscopy and fluoroscopy may be used
      adjunctively to assess fracture reduction and fixation. Arthoscopy further
      facilitates initial treatment by allowing direct joint visualisation,
      debridement, the removal of small free intra-articular fragments, and the
      recognition and early treatment of wrist ligament injuries, particularly those
      not appreciated by X-ray evaluation

PMID- 11301503
TI  - The treatment of unstable distal radius fractures with volar fixation.
AB  - Stable internal fixation and early motion has not been routinely available for
      distal radius fractures. Difficulties with the dorsal approach discourage
      surgeons from internally fixing the most common fracture types. The introduction
      of a new volar plate with subchondral support fixation allows the treatment of
      most distal radius fractures with stable internal fixation and early motion while
      avoiding the complications inherent in the dorsal approach.

PMID- 11301504
TI  - Early wrist arthrodesis for irreparable intra-articular distal radial fractures.
AB  - When articular restoration and congruity cannot be accomplished in distal radial
      fractures owing to severe articular bone loss or comminution, early wrist
      arthrodesis should be considered. This procedure rapidly restores wrist alignment
      and stability and controls pain. Arthrodesis is a highly reliable and definitive
      procedure that optimises the opportunity for early functional and occupational
      recovery while minimising the risks of developing stiff digits or chronic pain in
      injuries otherwise doomed from the start of treatment to result in severe wrist
      stiffness and post-traumatic arthritis. Simultaneous proximal row carpectomy or
      the use of ipsilateral local bone graft donor sites, such as the distal radius or
      proximal ulna, decrease both initial treatment and hospital costs and morbidity.
      Wrist arthrodesis is also effective when polytrauma or multiple fractures co
      exist. Successful early treatment may expedite return to work and reduce lost
      time and wages resulting from the injury.

PMID- 11301505
TI  - Hand and distal forearm replantation--immediate and long-term follow-up.
AB  - Six cases of traumatic amputation of hand and/or forearm were treated by
      replantation over the last 20 years at this hospital. Reattachment was successful
      in all of the cases. Success was largely due to proper selection of cases,
      meticulous technique and availability of skilled manpower and technological help.
      Although survival of replanted part was achieved in all cases, functional success
      was not uniform as revealed by subjective and objective criteria used during
      evaluation and follow-up. Tamai method of scoring the functional aspect of a
      replanted part not only indicates the functional ability of a replanted part but
      also creates uniformity in data collection for easier comparison with other
      reported series.

PMID- 11301506
TI  - Metacarpal and proximal phalangeal fractures--fixation with multiple
      intramedullary Kirschner wires.
AB  - The use of intramedullary wires for fixation of fractures of the metacarpal and
      proximal phalanx in our hospital was reviewed. Twenty-six patients with 26
      metacarpal fractures and four proximal phalangeal fractures were treated using
      this technique from 1993 to 1998. After a minimal follow-up of nine months, all
      the patients were assessed clinically and radiologically. All fractures proceeded
      to bony union at an average of 5.7 weeks (range four to eight weeks). With this
      simple and minimally invasive technique, most of these patients required very
      short hospital stay and were able to start mobilisation relatively early. The
      general outcome was good hand function with few complications.

PMID- 11301507
TI  - Fracture of hamate hook--diagnosis by the hamate hook lateral view.
AB  - Ten intact wrist joints were examined to evaluate the hamate hook visualisation
      by a hamate hook lateral radiographic view. Results of the study indicated that
      this 30 degrees -tilted lateral wrist radiographic projection with palmar
      abduction of the thumb clearly revealed the hamate hook from its base to the tip
      in the first web space away from the metacarpal bases and carpal bones. This
      radiographic technique was applied on patients who experienced pain at the
      hypothenar eminence. Fracture can be detected at the hamate hook in two cases and
      bilateral bipartite hamulus in one case. This specific supplementary projection
      is recommended in patients with the relevant physical signs.

PMID- 11301508
TI  - The simple wrist ganglion--more than a minor surgical procedure?
AB  - The operative results of 59 wrist ganglions over a ten-year period are reported.
      The mean follow-up time was 65 months (range: 6-133). The indication for
      operation was pre-operative pain in 68% of cases (40 ganglions) and cosmetic
      deformity in 32% of cases (19 ganglions). There were six recurrences (10%) at a
      mean duration of 40 months post-operatively (range: 5-70). There was no
      statistical differences between recurrences comparing dorsal versus volar
      ganglions using the chi-squared analysis. Two occult recurrences were detected on
      follow-up ultrasound examination giving an overall recurrence rate of 14%.
      Despite 92% of patients being satisfied with the operative procedure, there were
      16 patients (28%) who had either persistent pain, limitation of function, were
      unsatisfied or had a recurrence. These results show that treatment of a simple
      ganglion is more than just a minor operation.

PMID- 11301509
TI  - Conservative treatment of intra-articular fractures of the distal radius--factors
      affecting functional outcome.
AB  - One hundred and eleven intra-articular fractures of the distal radius in young
      adults that were conservatively treated were studied. At two years, 80% of
      fractures were rated as excellent or good by the modified Green and O'Brien
      scoring system. The rate of re-displacement within casts was 28%. Sixty five per
      cent of re-displaced fractures were treated with surgical fixation. Those re
      displaced fractures treated with repeated manipulation had only 33% excellent or
      good result. Moreover, their initial alignment could not be preserved. Axial
      compression (>2 mm) and dorsal angulation (>15 degrees ) were directly related to
      worse functional outcome and diminished range of motion.

PMID- 11301510
TI  - Scaphoid mal-union--current concept and perspectives.

PMID- 11301511
TI  - Proximal radioulnar synostosis treated with a free vascularised fascio-fat graft-
      report of two cases.

PMID- 11301512
TI  - Traumatic rupture of the extensor digitorum communis and extensor digiti minimi
      at the musculotendinous junction associated with volar dislocation of the distal
      radioulnar joint--a case report.

PMID- 11301513
TI  - An unusual hand injury caused by powered woodsplitter--split fingers.
AB  - We present a case of very unusual injury to the right hand of a 14-year-old boy
      who had an accident with a powered woodsplitter. The trauma produced a unique
      hand injury pattern. All fingers except the thumb were split into dorsal and
      volar sections without any bone fractures, mimicking surgically elevated volar
      flaps. We achieved satisfactory hand function using simple surgical and
      conservative management in this unique hand injury case.

PMID- 11301514
TI  - Isolated dorsal dislocation of the 5th carpometacarpal joint.
AB  - Injuries to the carpometacarpal (CMC) joints are uncommon injuries and isolated
      dislocation of these joints occurs very infrequently. The 4th and 5th CMC joints
      are predominantly involved in CMC joint injuries. The detection of CMC joint
      injuries requires a high index of suspicion and often depends on special
      radiographic views. This article present a case report of a mid-shaft fracture of
      the 4th metacarpal which was associated with an isolated dislocation of the 5th
      CMC joint. An overview of the incidence, mechanism of injury, anatomy, clinical
      and radiological assessment of injuries involving dorsal dislocation of the 5th
      carpometacarpal joint is presented.

PMID- 11301515
TI  - Recurrent synovial chondromatosis of the index finger--case report and literature
      review.
AB  - We report a case of synovial chondromatosis of the proximal interphalangeal joint
      of the dominant right index finger with a follow-up of four years. The lesion
      recurred within a year of complete excision of the fibrous sac containing
      cartilaginous nodules. Despite early recurrence and extensive calcification
      around the proximal phalanx, no malignant changes were noted on histological
      examination. The patient remains asymptomatic for two years after the second
      operation.

PMID- 11301516
TI  - Osteoid osteoma of the lunate--a case report.
AB  - We report a rare case of an osteoid osteoma of the lunate bone in a young lady
      who presented to us with chronic wrist pain. She was treated by excision and
      cancellous bone grafting of the lesion with complete resolution of symptoms.

PMID- 11301517
TI  - Is vision continuous with cognition? The case for cognitive impenetrability of
      visual perception.
AB  - Although the study of visual perception has made more progress in the past 40
      years than any other area of cognitive science, there remain major disagreements
      as to how closely vision is tied to cognition. This target article sets out some
      of the arguments for both sides (arguments from computer vision, neuroscience,
      psychophysics, perceptual learning, and other areas of vision science) and
      defends the position that an important part of visual perception, corresponding
      to what some people have called early vision, is prohibited from accessing
      relevant expectations, knowledge, and utilities in determining the function it
      computes--in other words, it is cognitively impenetrable. That part of vision is
      complex and involves top-down interactions that are internal to the early vision
      system. Its function is to provide a structured representation of the 3-D
      surfaces of objects sufficient to serve as an index into memory, with somewhat
      different outputs being made available to other systems such as those dealing
      with motor control. The paper also addresses certain conceptual and
      methodological issues raised by this claim, such as whether signal detection
      theory and event-related potentials can be used to assess cognitive penetration
      of vision. A distinction is made among several stages in visual processing,
      including, in addition to the inflexible early-vision stage, a pre-perceptual
      attention-allocation stage and a post-perceptual evaluation, selection, and
      inference stage, which accesses long-term memory. These two stages provide the
      primary ways in which cognition can affect the outcome of visual perception. The
      paper discusses arguments from computer vision and psychology showing that vision
      is "intelligent" and involves elements of "problem solving." The cases of
      apparently intelligent interpretation sometimes cited in support of this claim do
      not show cognitive penetration; rather, they show that certain natural
      constraints on interpretation, concerned primarily with optical and geometrical
      properties of the world, have been compiled into the visual system. The paper
      also examines a number of examples where instructions and "hints" are alleged to
      affect what is seen. In each case it is concluded that the evidence is more
      readily assimilated to the view that when cognitive effects are found, they have
      a locus outside early vision, in such processes as the allocation of focal
      attention and the identification of the stimulus.

PMID- 11301518
TI  - Episodic memory, amnesia, and the hippocampal-anterior thalamic axis.
AB  - By utilizing new information from both clinical and experimental (lesion,
      electrophysiological, and gene-activation) studies with animals, the anatomy
      underlying anterograde amnesia has been reformulated. The distinction between
      temporal lobe and diencephalic amnesia is of limited value in that a common
      feature of anterograde amnesia is damage to part of an "extended hippocampal
      system" comprising the hippocampus, the fornix, the mamillary bodies, and the
      anterior thalamic nuclei. This view, which can be traced back to Delay and Brion
      (1969), differs from other recent models in placing critical importance on the
      efferents from the hippocampus via the fornix to the diencephalon. These are
      necessary for the encoding and, hence, the effective subsequent recall of
      episodic memory. An additional feature of this hippocampal-anterior thalamic axis
      is the presence of projections back from the diencephalon to the temporal cortex
      and hippocampus that also support episodic memory. In contrast, this hippocampal
      system is not required for tests of item recognition that primarily tax
      familiarity judgements. Familiarity judgements reflect an independent process
      that depends on a distinct system involving the perirhinal cortex of the temporal
      lobe and the medial dorsal nucleus of the thalamus. In the large majority of
      amnesic cases both the hippocampal-anterior thalamic and the perirhinal-medial
      dorsal thalamic systems are compromised, leading to severe deficits in both
      recall and recognition.

PMID- 11301519
TI  - Neurobiology of the structure of personality: dopamine, facilitation of incentive
      motivation, and extraversion.
AB  - Extraversion has two central characteristics: (1) interpersonal engagement, which
      consists of affiliation (enjoying and valuing close interpersonal bonds, being
      warm and affectionate) and agency (being socially dominant, enjoying leadership
      roles, being assertive, being exhibitionistic, and having a sense of potency in
      accomplishing goals) and (2) impulsivity, which emerges from the interaction of
      extraversion and a second, independent trait (constraint). Agency is a more
      general motivational disposition that includes dominance, ambition, mastery,
      efficacy, and achievement. Positive affect (a combination of positive feelings
      and motivation) is closely associated with extraversion. Extraversion is
      accordingly based on positive incentive motivation. Parallels between
      extraversion (particularly its agency component) and a mammalian behavioral
      approach system based on positive incentive motivation implicate a
      neuroanatomical network and modulatory neurotransmitters in the processing of
      incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates
      the salient incentive context in the medial orbital cortex, amygdala, and
      hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit
      composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area
      dopamine projection system; and (3) creates an incentive motivational state that
      can be transmitted to the motor system. Individual differences in the functioning
      of this network arise from functional variation in the ventral tegmental area
      dopamine projections, which are directly involved in coding the intensity of
      incentive motivation. The animal evidence suggests that there are three
      neurodevelopmental sources of individual differences in dopamine: genetic,
      "experience-expectant," and "experience-dependent." Individual differences in
      dopamine promote variation in the heterosynaptic plasticity that enhances the
      connection between incentive context and incentive motivation and behavior. Our
      psychobiological threshold model explains the effects of individual differences
      in dopamine transmission on behavior, and their relation to personality traits is
      discussed.

PMID- 11301520
TI  - A theory of lexical access in speech production.
AB  - Preparing words in speech production is normally a fast and accurate process. We
      generate them two or three per second in fluent conversation; and overtly naming
      a clear picture of an object can easily be initiated within 600 msec after
      picture onset. The underlying process, however, is exceedingly complex. The
      theory reviewed in this target article analyzes this process as staged and feed
      forward. After a first stage of conceptual preparation, word generation proceeds
      through lexical selection, morphological and phonological encoding, phonetic
      encoding, and articulation itself. In addition, the speaker exerts some degree of
      output control, by monitoring of self-produced internal and overt speech. The
      core of the theory, ranging from lexical selection to the initiation of phonetic
      encoding, is captured in a computational model, called WEAVER++. Both the theory
      and the computational model have been developed in interaction with reaction time
      experiments, particularly in picture naming or related word production paradigms,
      with the aim of accounting for the real-time processing in normal word
      production. A comprehensive review of theory, model, and experiments is
      presented. The model can handle some of the main observations in the domain of
      speech errors (the major empirical domain for most other theories of lexical
      access), and the theory opens new ways of approaching the cerebral organization
      of speech production by way of high-temporal-resolution imaging.

PMID- 11301521
TI  - A connectionist theory of phenomenal experience.
AB  - When cognitive scientists apply computational theory to the problem of phenomenal
      consciousness, as many have been doing recently, there are two fundamentally
      distinct approaches available. Consciousness is to be explained either in terms
      of the nature of the representational vehicles the brain deploys or in terms of
      the computational processes defined over these vehicles. We call versions of
      these two approaches vehicle and process theories of consciousness, respectively.
      However, although there may be space for vehicle theories of consciousness in
      cognitive science, they are relatively rare. This is because of the influence
      exerted, on the one hand, by a large body of research that purports to show that
      the explicit representation of information in the brain and conscious experience
      are dissociable, and on the other, by the classical computational theory of mind-
      the theory that takes human cognition to be a species of symbol manipulation. Two
      recent developments in cognitive science combine to suggest that a reappraisal of
      this situation is in order. First, a number of theorists have recently been
      highly critical of the experimental methodologies used in the dissociation
      studies--so critical, in fact, that it is no longer reasonable to assume that the
      dissociability of conscious experience and explicit representation has been
      adequately demonstrated. Second, classicism, as a theory of human cognition, is
      no longer as dominant in cognitive science as it once was. It now has a lively
      competitor in the form of connectionism; and connectionism, unlike classicism,
      does have the computational resources to support a robust vehicle theory of
      consciousness. In this target article we develop and defend this connectionist
      vehicle theory of consciousness. It takes the form of the following simple
      empirical hypothesis: phenomenal experience consists of the explicit
      representation of information in neurally realized parallel distributed
      processing (PDP) networks. This hypothesis leads us to reassess some common
      wisdom about consciousness, but, we argue, in fruitful and ultimately plausible
      ways.

PMID- 11301522
TI  - Verbal working memory and sentence comprehension.
AB  - This target article discusses the verbal working memory system used in sentence
      comprehension. We review the concept of working memory as a short-duration system
      in which small amounts of information are simultaneously stored and manipulated
      in the service of accomplishing a task. We summarize the argument that syntactic
      processing in sentence comprehension requires such a storage and computational
      system. We then ask whether the working memory system used in syntactic
      processing is the same as that used in verbally mediated tasks that involve
      conscious controlled processing. Evidence is brought to bear from various
      sources: the relationship between individual differences in working memory and
      individual differences in the efficiency of syntactic processing; the effect of
      concurrent verbal memory load on syntactic processing; and syntactic processing
      in patients with poor short-term memory, patients with poor working memory, and
      patients with aphasia. Experimental results from these normal subjects and
      patients with various brain lesions converge on the conclusion that there is a
      specialization in the verbal working memory system for assigning the syntactic
      structure of a sentence and using that structure in determining sentence meaning
      that is separate from the working memory system underlying the use of sentence
      meaning to accomplish other functions. We present a theory of the divisions of
      the verbal working memory system and suggestions regarding its neural basis.

PMID- 11301523
TI  - Staying alive: evolution, culture, and women's intrasexual aggression.
AB  - Females' tendency to place a high value on protecting their own lives enhanced
      their reproductive success in the environment of evolutionary adaptation because
      infant survival depended more upon maternal than on paternal care and defence.
      The evolved mechanism by which the costs of aggression (and other forms of risk
      taking) are weighted more heavily for females may be a lower threshold for fear
      in situations which pose a direct threat of bodily injury. Females' concern with
      personal survival also has implications for sex differences in dominance
      hierarchies because the risks associated with hierarchy formation in nonbonded
      exogamous females are not offset by increased reproductive success. Hence among
      females, disputes do not carry implications for status with them as they do among
      males, but are chiefly connected with the acquisition and defence of scarce
      resources. Consequently, female competition is more likely to take the form of
      indirect aggression or low-level direct combat than among males. Under
      patriarchy, men have held the power to propagate images and attributions which
      are favourable to the continuance of their control. Women's aggression has been
      viewed as a gender-incongruent aberration or dismissed as evidence of
      irrationality. These cultural interpretations have "enhanced" evolutionarily
      based sex differences by a process of imposition which stigmatises the expression
      of aggression by females and causes women to offer exculpatory (rather than
      justificatory) accounts of their own aggression.

PMID- 11301524
TI  - Words in the brain's language.
AB  - If the cortex is an associative memory, strongly connected cell assemblies will
      form when neurons in different cortical areas are frequently active at the same
      time. The cortical distributions of these assemblies must be a consequence of
      where in the cortex correlated neuronal activity occurred during learning. An
      assembly can be considered a functional unit exhibiting activity states such as
      full activation ("ignition") after appropriate sensory stimulation (possibly
      related to perception) and continuous reverberation of excitation within the
      assembly (a putative memory process). This has implications for cortical
      topographies and activity dynamics of cell assemblies forming during language
      acquisition, in particular for those representing words. Cortical topographies of
      assemblies should be related to aspects of the meaning of the words they
      represent, and physiological signs of cell assembly ignition should be followed
      by possible indicators of reverberation. The following postulates are discussed
      in detail: (1) assemblies representing phonological word forms are strongly
      lateralized and distributed over perisylvian cortices; (2) assemblies
      representing highly abstract words such as grammatical function words are also
      strongly lateralized and restricted to these perisylvian regions; (3) assemblies
      representing concrete content words include additional neurons in both
      hemispheres; (4) assemblies representing words referring to visual stimuli
      include neurons in visual cortices; and (5) assemblies representing words
      referring to actions include neurons in motor cortices. Two main sources of
      evidence are used to evaluate these proposals: (a) imaging studies focusing on
      localizing word processing in the brain, based on stimulus-triggered event
      related potentials (ERPs), positron emission tomography (PET), and functional
      magnetic resonance imaging (fMRI), and (b) studies of the temporal dynamics of
      fast activity changes in the brain, as revealed by high-frequency responses
      recorded in the electroencephalogram (EEG) and magnetoencephalogram (MEG). These
      data provide evidence for processing differences between words and matched
      meaningless pseudowords, and between word classes, such as concrete content and
      abstract function words, and words evoking visual or motor associations. There is
      evidence for early word class-specific spreading of neuronal activity and for
      equally specific high-frequency responses occurring later. These results support
      a neurobiological model of language in the Hebbian tradition. Competing large
      scale neuronal theories of language are discussed in light of the data
      summarized. Neurobiological perspectives on the problem of serial order of words
      in syntactic strings are considered in closing.

PMID- 11301525
TI  - Perceptual symbol systems.
AB  - Prior to the twentieth century, theories of knowledge were inherently perceptual.
      Since then, developments in logic, statistics, and programming languages have
      inspired amodal theories that rest on principles fundamentally different from
      those underlying perception. In addition, perceptual approaches have become
      widely viewed as untenable because they are assumed to implement recording
      systems, not conceptual systems. A perceptual theory of knowledge is developed
      here in the context of current cognitive science and neuroscience. During
      perceptual experience, association areas in the brain capture bottom-up patterns
      of activation in sensory-motor areas. Later, in a top-down manner, association
      areas partially reactivate sensory-motor areas to implement perceptual symbols.
      The storage and reactivation of perceptual symbols operates at the level of
      perceptual components--not at the level of holistic perceptual experiences.
      Through the use of selective attention, schematic representations of perceptual
      components are extracted from experience and stored in memory (e.g., individual
      memories of green, purr, hot). As memories of the same component become organized
      around a common frame, they implement a simulator that produces limitless
      simulations of the component (e.g., simulations of purr). Not only do such
      simulators develop for aspects of sensory experience, they also develop for
      aspects of proprioception (e.g., lift, run) and introspection (e.g., compare,
      memory, happy, hungry). Once established, these simulators implement a basic
      conceptual system that represents types, supports categorization, and produces
      categorical inferences. These simulators further support productivity,
      propositions, and abstract concepts, thereby implementing a fully functional
      conceptual system. Productivity results from integrating simulators
      combinatorially and recursively to produce complex simulations. Propositions
      result from binding simulators to perceived individuals to represent type-token
      relations. Abstract concepts are grounded in complex simulations of combined
      physical and introspective events. Thus, a perceptual theory of knowledge can
      implement a fully functional conceptual system while avoiding problems associated
      with amodal symbol systems. Implications for cognition, neuroscience, evolution,
      development, and artificial intelligence are explored.

PMID- 11301526
TI  - A model of saccade generation based on parallel processing and competitive
      inhibition.
AB  - During active vision, the eyes continually scan the visual environment using
      saccadic scanning movements. This target article presents an information
      processing model for the control of these movements, with some close parallels to
      established physiological processes in the oculomotor system. Two separate
      pathways are concerned with the spatial and the temporal programming of the
      movement. In the temporal pathway there is spatially distributed coding and the
      saccade target is selected from a "salience map." Both pathways descend through a
      hierarchy of levels, the lower ones operating automatically. Visual onsets have
      automatic access to the eye control system via the lower levels. Various centres
      in each pathway are interconnected via reciprocal inhibition. The model accounts
      for a number of well-established phenomena in target-elicited saccades: the gap
      effect, express saccades, the remote distractor effect, and the global effect.
      High-level control of the pathways in tasks such as visual search and reading is
      discussed; it operates through spatial selection and search selection, which
      generally combine in an automated way. The model is examined in relation to data
      from patients with unilateral neglect.

PMID- 11301527
TI  - Clinical considerations in cement selection for provisional restorations--Part 2.

PMID- 11301528
TI  - Determination and communication of color using the five color dimensions of
      teeth.
AB  - The determination and communication of color in dentistry is based on dated
      concepts that cause difficulty for clinicians and technicians who use their
      personal experiences to interpret this parameter, which is so important in
      aesthetic care. In this article, the author proposes a concept of color that has
      evolved from the observation and study of extracted and in vivo natural
      dentition. This research has been performed with the aim of providing the
      clinician with a predictable method of determining color from clinical evidence.

PMID- 11301529
TI  - Fluorapatite-leucite glass ceramic veneers for aesthetic anterior restorations.

PMID- 11301530
TI  - Seating and cementation of a crown restoration in a crowded anterior mandible.

PMID- 11301531
TI  - Clinical considerations for aesthetic laboratory-fabricated inlay/onlay
      restorations: a review.
AB  - The continued evolution of adhesive technology and materials has increased the
      application of composite materials for the direct and indirect restoration of
      posterior dentition. While these innovations cannot address every restorative
      challenge, such developments do allow clinicians to use conservative preparation
      designs and varying surface treatments in their efforts to achieve functional and
      aesthetic results. This discussion details the comprehensive clinical protocol
      required to use laboratory-fabricated resin systems for inlay/onlay restorations.

PMID- 11301532
TI  - Treatment of gingival recession with a modified "tunnel" technique and an
      acellular dermal connective tissue allograft.
AB  - The treatment of gingival recession through the creation of a "tunnel" beneath
      the buccal mucosa allows coronal repositioning the soft tissue with predictable
      root coverage and aesthetics. Vertical incisions on either side of this tunnel
      preparation enable placement of a connective tissue graft within the tunnel. The
      use of an acellular dermal connective tissue allograft permits grafting of
      multiple sites without the need for a donor tissue surgical site or additional
      visits. This article demonstrates a modified tunnel technique and a case
      presentation that incorporates this procedure.

PMID- 11301533
TI  - Educational dental meetings.

PMID- 11301534
TI  - Clinicopathologic findings, sensitivity to house dust mites and efficacy of
      milbemycin oxime treatment of dogs with Cheyletiella sp. infestation.
AB  - Twenty-three dogs with positive skin scrapings for Cheyletiella sp. were treated
      with milbemycin oxime using a protocol approximating 2 mg kg-1 orally once weekly
      for three weeks. Nineteen of these dogs belonged to a household of 41 dogs and
      two dogs were in households with one other dog. All in-contact dogs were treated.
      Pre-treatment intradermal skin tests showed positive reactions to D. farinae in
      13 dogs and to D. pteronyssinus in 12 dogs; these became negative post-treatment
      in four and seven dogs, respectively. All dogs showed a dramatic reduction in
      clinical signs one week after the third treatment. Eighteen dogs no longer had
      mites on skin scrapings, three had dead mites and two had deformed eggs.
      Recurrence of clinical signs necessitated two additional courses of the protocol
      in the multiple dog household and for a dog receiving immunosuppressive treatment
      for pemphigus foliaceus. Possible adverse reactions to the milbemycin (vomiting,
      lethargy) were noted once in two dogs.

PMID- 11301535
TI  - Ulcerative dermatosis of the Shetland sheepdog and rough collie dog may represent
      a novel vesicular variant of cutaneous lupus erythematosus.
AB  - A syndrome of ulcerative dermatitis (UDSSC) previously has been described as
      unique to the Shetland sheepdog and rough collie dog. The pathogenesis of this
      disease is poorly understood and it has been suggested that it may be a variant
      of canine dermatomyositis (DM) which is also seen in these breeds. Information on
      the clinical presentation and previous medical history was collected from five
      Shetland sheepdogs and three rough collie dogs previously diagnosed with UDSSC.
      Characteristic features of the disease were adult onset in the summer months with
      annular, polycyclic and serpiginous ulcerations distributed over sparsely haired
      areas of the body. Skin biopsies taken from active lesions were compared in a
      blinded fashion with histological sections from seven Shetland sheepdogs and one
      rough collie with DM. Dermatomyositis was characterized histologically as a cell
      poor interface dermatitis associated with follicular atrophy. In contrast, the
      lesional pattern of UDSSC is that of a lymphocyte-rich interface dermatitis and
      folliculitis with vesiculation at the dermal-epidermal junction. The authors
      conclude that these represent two distinct diseases and that UDSSC may be a
      vesicular form of cutaneous lupus erythematosus seen in the adult rough collie
      dog and Shetland sheepdog.

PMID- 11301536
TI  - Clinical and histological evaluation of an analogue of palmitoylethanolamide, PLR
      120 (comicronized Palmidrol INN) in cats with eosinophilic granuloma and
      eosinophilic plaque: a pilot study.
AB  - Fifteen cats with eosinophilic granuloma or eosinophilic plaque were given PLR
      120 at the dosage of 10 mg kg-1 twice daily for one month. PLR-120 down-modulates
      mast cell degranulation via a receptor-mediated mechanism. No other drugs were
      permitted and cats were kept free of parasites throughout the study. A clinical
      evaluation and skin biopsies were performed before and after the treatment.
      Clinical improvement was assessed at 15 and 30 days. Mast cell numbers were
      counted and their granular content was assessed by densitometric analysis on
      toluidine blue-stained sections before and after the treatment. Ten of 15 (67%)
      cats showed clinical improvement of signs and lesions. There was no significant
      difference between mast cell numbers in skin biopsies taken before and after the
      trial, whereas the number of granules was significantly increased (P < 0.009).
      This pilot study suggests that PLR-120 might be a useful drug for the treatment
      of eosinophilic granuloma and eosinophilic plaque.

PMID- 11301537
TI  - Sulphido-leukotriene production from peripheral leukocytes and skin in clinically
      normal dogs and house dust mite positive atopic dogs.
AB  - Pathogenesis of canine atopy has not been completely elucidated. In humans,
      sulphido-leukotrienes (s-LT) play a role in atopy, and increased production of s
      LT occurs in the skin and peripheral leukocytes after allergen challenge. The
      study population included 16 clinically normal and 13 atopic dogs. All atopic
      dogs had in common a positive reaction (4+) to the intradermal injection of house
      dust mite (allergen of reference). Blood samples and skin biopsies were
      collected. Sulphido-LT synthesis by peripheral leukocytes after stimulation was
      measured, and no statistically significant difference was found between
      clinically normal and atopic dogs. Sulphido-LT concentrations in skin samples
      from stimulated and unstimulated sites were measured, and no statistically
      significant difference was detected between clinically normal and atopic dogs or
      between lesional and nonlesional skin within the atopic group. Clinical signs of
      atopic dogs were graded by owners and no correlation was found between their
      severity and cutaneous concentrations of s-LT. In this study there was no
      increase in s-LT synthesis in atopic dogs.

PMID- 11301538
TI  - Rapid identification of tissue micro-organisms in skin biopsy specimens from
      domestic animals using polyclonal BCG antibody.
AB  - Immunostaining with polyclonal anti-Mycobacterium bovis (BCG) was evaluated as a
      single screening method for the histological identification of micro-organisms in
      skin biopsy specimens from various veterinary species. Confirmed archival cases
      infected with Mycobacteria, Nocardia, Actinobacillus, Actinomyces,
      Streptococcus/Staphylococcus, Dermatophilus, spirochetes, Blastomyces,
      Coccidioides, Cryptococcus, Histoplasma, dermatophytes, Malassezia, Sporothrix,
      Leishmania, Pythium, phaeohyphomycetes and Prototheca organisms were selected. A
      total of 70 skin biopsy specimens from the dog, cat, horse, ox and llama were
      evaluated. The anti-BCG immunostain labelled bacteria and fungi with high
      sensitivity and minimal background staining but did not label spirochetes and
      protozoa (Leishmania). Differences were not noted between veterinary species. The
      results indicate that immunostaining with polyclonal anti-BCG is a suitable
      screening technique for the rapid identification of most common bacterial and
      fungal organisms in paraffin-embedded specimens. Also, mycobacterial and
      nocardial organisms were identified more readily with the anti-BCG immunostain in
      comparison to the histochemical stains.

PMID- 11301539
TI  - Characterization of the inflammatory infiltrate during IgE-mediated late phase
      reactions in the skin of normal and atopic dogs.
AB  - In canine and human atopic patients, the intracutaneous injection of offending
      allergens is followed by the development of both immediate and late-phase
      reactions. The present study was performed to expand on the characterization and
      dynamics of inflammatory cell subsets during IgE-mediated late-phase reactions in
      canine skin. Three normal dogs and three Dermatophagoides farinae-allergic dogs
      were selected for this experiment. All dogs were challenged intradermally with
      mite allergen, purified anticanine IgE antibodies (positive control) or phosphate
      buffered saline (negative control). Skin biopsies were obtained before and 6, 12
      and 24 h post-injection. Sections were stained with metachromatic and eosinophil
      specific histological stains. Additionally, we used an immunohistochemical method
      with antibodies specific for canine leukocyte antigens. This study confirmed the
      occurrence of a late-phase reaction in atopic skin following allergen challenge,
      and in normal and atopic canine skin after intradermal injection of IgE-specific
      antibodies. Whereas early emigrating dermal cells were composed chiefly of
      neutrophil and activated eosinophil granulocytes, there was an influx of alpha
      beta T-lymphocytes and dermal dendritic cells in later stages of the late-phase
      reactions. Because IgE-mediated late-phase reactions resemble spontaneous atopic
      canine skin lesions, both at macroscopic and microscopic levels, we propose the
      use of similar challenges to study the anti-inflammatory effects of anti-allergic
      drugs in a pre-clinical setting.

PMID- 11301540
TI  - Dermatophilus-like infection in beluga whales, Delphinapterus leucas, from the
      St. Lawrence estuary.
AB  - Six beluga whales (Delphinapterus leucas) found dead on the shores of the St.
      Lawrence estuary had multiple slightly depressed greyish round areas randomly
      distributed over the whole body. Histologically, the surface of these areas was
      covered with a thick layer of Dermatophilus-like organisms which invaded the
      stratum corneum. The underlying stratum spinosum had marked spongiosis and
      vacuolar degeneration. Minimal neutrophilic infiltration was present within the
      underlying dermal papillae. To the authors' knowledge, dermatophilosis in
      cetaceans has not been reported previously.

PMID- 11301541
TI  - Connectionist modelling in psychology: a localist manifesto.
AB  - Over the last decade, fully distributed models have become dominant in
      connectionist psychological modelling, whereas the virtues of localist models
      have been underestimated. This target article illustrates some of the benefits of
      localist modelling. Localist models are characterized by the presence of localist
      representations rather than the absence of distributed representations. A
      generalized localist model is proposed that exhibits many of the properties of
      fully distributed models. It can be applied to a number of problems that are
      difficult for fully distributed models, and its applicability can be extended
      through comparisons with a number of classic mathematical models of behaviour.
      There are reasons why localist models have been underused, though these often
      misconstrue the localist position. In particular, many conclusions about
      connectionist representation, based on neuroscientific observation, can be called
      into question. There are still some problems inherent in the application of fully
      distributed systems and some inadequacies in proposed solutions to these
      problems. In the domain of psychological modelling, localist modelling is to be
      preferred.

PMID- 11301542
TI  - Precis of Neural organization: structure, function, and dynamics.
AB  - NEURAL ORGANIZATION: Structure, function, and dynamics shows how theory and
      experiment can supplement each other in an integrated, evolving account of the
      brain's structure, function, and dynamics. (1) STRUCTURE: Studies of brain
      function and dynamics build on and contribute to an understanding of many brain
      regions, the neural circuits that constitute them, and their spatial relations.
      We emphasize Szentagothai's modular architectonics principle, but also stress the
      importance of the microcomplexes of cerebellar circuitry and the lamellae of
      hippocampus. (2) FUNCTION: Control of eye movements, reaching and grasping,
      cognitive maps, and the roles of vision receive a functional decomposition in
      terms of schemas. Hypotheses as to how each schema is implemented through the
      interaction of specific brain regions provide the basis for modeling the overall
      function by neural networks constrained by neural data. Synthetic PET integrates
      modeling of primate circuitry with data from human brain imaging. (3) DYNAMICS:
      Dynamic system theory analyzes spatiotemporal neural phenomena, such as
      oscillatory and chaotic activity in both single neurons and (often synchronized)
      neural networks, the self-organizing development and plasticity of ordered neural
      structures, and learning and memory phenomena associated with synaptic
      modification. Rhythm generation involves multiple levels of analysis, from
      intrinsic cellular processes to loops involving multiple brain regions. A variety
      of rhythms are related to memory functions. The Precis presents a multifaceted
      case study of the hippocampus. We conclude with the claim that language and other
      cognitive processes can be fruitfully studied within the framework of neural
      organization that the authors have charted with John Szentagothai.

PMID- 11301543
TI  - The evolution of human mating: trade-offs and strategic pluralism.
AB  - During human evolutionary history, there were "trade-offs" between expending time
      and energy on child-rearing and mating, so both men and women evolved conditional
      mating strategies guided by cues signaling the circumstances. Many short-term
      matings might be successful for some men; others might try to find and keep a
      single mate, investing their effort in rearing her offspring. Recent evidence
      suggests that men with features signaling genetic benefits to offspring should be
      preferred by women as short-term mates, but there are trade-offs between a mate's
      genetic fitness and his willingness to help in child-rearing. It is these
      circumstances and the cues that signal them that underlie the variation in short-
      and long-term mating strategies between and within the sexes.

PMID- 11301544
TI  - Individual differences in reasoning: implications for the rationality debate?
AB  - Much research in the last two decades has demonstrated that human responses
      deviate from the performance deemed normative according to various models of
      decision making and rational judgment (e.g., the basic axioms of utility theory).
      This gap between the normative and the descriptive can be interpreted as
      indicating systematic irrationalities in human cognition. However, four
      alternative interpretations preserve the assumption that human behavior and
      cognition is largely rational. These posit that the gap is due to (1) performance
      errors, (2) computational limitations, (3) the wrong norm being applied by the
      experimenter, and (4) a different construal of the task by the subject. In the
      debates about the viability of these alternative explanations, attention has been
      focused too narrowly on the model response. In a series of experiments involving
      most of the classic tasks in the heuristics and biases literature, we have
      examined the implications of individual differences in performance for each of
      the four explanations of the normative/descriptive gap. Performance errors are a
      minor factor in the gap; computational limitations underlie non-normative
      responding on several tasks, particularly those that involve some type of
      cognitive decontextualization. Unexpected patterns of covariance can suggest when
      the wrong norm is being applied to a task or when an alternative construal of the
      task should be considered appropriate.

PMID- 11301545
TI  - Precis of Simple heuristics that make us smart.
AB  - How can anyone be rational in a world where knowledge is limited, time is
      pressing, and deep thought is often an unattainable luxury? Traditional models of
      unbounded rationality and optimization in cognitive science, economics, and
      animal behavior have tended to view decision-makers as possessing supernatural
      powers of reason, limitless knowledge, and endless time. But understanding
      decisions in the real world requires a more psychologically plausible notion of
      bounded rationality. In Simple heuristics that make us smart (Gigerenzer et al.
      1999), we explore fast and frugal heuristics--simple rules in the mind's adaptive
      toolbox for making decisions with realistic mental resources. These heuristics
      can enable both living organisms and artificial systems to make smart choices
      quickly and with a minimum of information by exploiting the way that information
      is structured in particular environments. In this precis, we show how simple
      building blocks that control information search, stop search, and make decisions
      can be put together to form classes of heuristics, including: ignorance-based and
      one-reason decision making for choice, elimination models for categorization, and
      satisficing heuristics for sequential search. These simple heuristics perform
      comparably to more complex algorithms, particularly when generalizing to new data
      -that is, simplicity leads to robustness. We present evidence regarding when
      people use simple heuristics and describe the challenges to be addressed by this
      research program.

PMID- 11301546
TI  - [Italy, autonomy of nursing in process].

PMID- 11301547
TI  - [Urinary catheterization].

PMID- 11301548
TI  - [Education of the diabetic patient--insulin injection and lipodystrophy].

PMID- 11301549
TI  - [The nurse, the handicapped patient with movement disorders and quality of life].

PMID- 11301550
TI  - [New international classification of disabilities].

PMID- 11301551
TI  - [Nursing care. Esthetic care and well-being].

PMID- 11301552
TI  - [Nursing care: pain, depression and quality of life].

PMID- 11301553
TI  - [Sexologic nursing care at the center of functional reeducation].

PMID- 11301554
TI  - [The "Return" project, quality of life after returning home from
      hospitalization].

PMID- 11301555
TI  - [The first nework of handicapped persons in France].

PMID- 11301556
TI  - [To avoid adding disabilities to disabilities].

PMID- 11301557
TI  - [Nursing care of the sites of implants].

PMID- 11301558
TI  - [Latex allergy].

PMID- 11301559
TI  - Matrix metalloproteinases and abdominal aortic aneurysms: a potential therapeutic
      target.
AB  - Abdominal aortic aneurysm (AAA) is a leading cause of death in the United States,
      and there is no effective treatment in the early course of disease. Therapy to
      retard or reverse aneurysmal growth requires an understanding of the underlying
      vascular pathology. Recent research has indicated that enzymatic degradation of
      structural matrix proteins plays a large role in the formation of AAAs.
      Specifically, many studies have implicated a family of matrix degrading enzymes,
      known as matrix metalloproteinases (MMPs), as vital factors in the disease.
      Although AAA was once thought to be purely secondary to atherosclerosis,
      investigators have demonstrated various differences between the diseases in both
      levels and distribution of MMPs, suggesting independent mechanisms. Experimental
      models have shown that inhibition of these proteinases may slow aortic wall
      matrix breakdown. The purpose of this article is to review the current literature
      regarding the role of individual MMPs in AAA, including their complex regulatory
      mechanisms and possible cellular sources, the importance of MMPs as a potential
      therapeutic target in the prevention and treatment of AAA, and their inhibition
      using novel pharmacologic interventions in animal models.

PMID- 11301560
TI  - Pharmacokinetics and pharmacodynamics of famotidine in infants.
AB  - The pharmacokinetics and pharmacodynamics of intravenous famotidine were
      evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic
      indication for the prophylactic treatment of stress ulceration. After a 0.5-mg/kg
      infusion of famotidine, timed serum (n = 6), urine (24-hour collection), and
      repeated measurements of gastric pH were obtained. The mean +/- standard
      deviation maximum plasma concentration (Cmax) was 640.66 +/- 250.66 ng/mL, the
      elimination half-life (t1/2 beta) was 10.51 +/- 5.43 hours, and the apparent
      volume of distribution at steady state (Vdss) was 0.82 +/- 0.29 L/kg. Plasma
      clearance (Cl) and renal clearance (ClR) were 0.132 +/- 0.061 L/hr/kg and 0.093
      +/- 0.056 L/hr/kg, respectively. No significant correlations were found between
      t1/2 beta, Vdss, Cl, and ClR and age. Six of the nine infants who had
      intragastric pH monitoring maintained a gastric pH > 4 until the final 24-hour
      sampling point. In this study, the t1/2 beta of famotidine was prolonged and the
      Vdss, Cl, ClR were reduced compared with corresponding parameters in previously
      reported studies of children older than one year of age and adults.

PMID- 11301561
TI  - Pharmacokinetic and pharmacodynamic characteristics and safety of inhaled
      albuterol enantiomers in healthy volunteers.
AB  - The pharmacokinetics and pharmacodynamics of inhaled albuterol given as single or
      multiple doses of racemate (RS-) or single enantiomers (R-, S-) were determined.
      In an open-label, three-way crossover, parallel-dose study, 1.25 and 5 mg of (R)-
      and (S)-albuterol and 2.5 and 10 mg of (RS)-albuterol were given via nebulization
      to 15 healthy volunteers. The pharmacokinetic parameters of each enantiomer were
      determined by noncompartmental and model-fitting analyses. Both (R)- and (S)
      albuterol showed rapid absorption and biexponential decline, with half-lives
      (t1/2) averaging 4 and 6 hours, respectively. There were no differences in
      pharmacokinetics of (R)-albuterol when administered as (R)- or (RS)-albuterol at
      the 5-mg dose with equivalent relative bioavailability as seen from maximum
      concentration (Cmax) and area under the concentration-time curve (AUC). The same
      was true for (S)-albuterol at the 1.25-mg and 5-mg doses. The data from 5-mg
      doses were considered to be more reliable due to assay sensitivity limitations,
      and indicated equivalent absorption and disposition of the individual
      enantiomers. There was no evidence of in vivo racemization, and (R)-albuterol did
      not interconvert to (S)-albuterol. Plasma potassium, plasma glucose, heart rate,
      and QTc interval were used in linear and Emax models to assess responses relating
      to (R)-albuterol concentrations. The Emax for potassium change was 1.32 meq/L,
      with an EC50 of 0.59 and 0.94 ng/mL after administration of (R)- and (RS)
      albuterol, respectively. The slopes and intercepts for glucose and heart rate
      changes were similar after administration of (R)- and (RS)-albuterol. No
      concentration-effect relationships were evident for QTc interval or for (S)
      albuterol. The extrapulmonary responses of (R)-albuterol and adverse effects were
      similar for single R-enantiomer or the racemic mixture.

PMID- 11301562
TI  - Lipid and lipoprotein responses to oral combined hormone replacement therapy in
      normolipemic obese women with controlled type 2 diabetes mellitus.
AB  - This study investigated the effects of oral combined hormone replacement therapy
      (OCHRT) on lipid concentrations and subpopulation distribution of lipoproteins in
      nine postmenopausal women with type 2 diabetes mellitus and moderate glycemic
      control. After 16 weeks of continuous daily therapy of conjugated estrogens 0.625
      mg and medroxyprogesterone 2.5 mg, the mean concentration of high-density
      lipoprotein (HDL) cholesterol showed a statistically significant increase of
      16.7%, predominantly in the HDL2 subfraction. No statistically significant
      changes in mean concentrations of total cholesterol, low-density lipoprotein
      (LDL) cholesterol, triglycerides, very low-density lipoprotein (VLDL)
      triglycerides, apolipoprotein A1, or apolipoprotein B were evident. Likewise, no
      changes were found in the average diameter of VLDL, LDL, or HDL particles;
      triglyceride concentrations of VLDL subfractions; cholesterol concentrations of
      LDL subfractions; or chemical composition of plasma LDL. These findings lend
      further support to the use of OCHRT in postmenopausal women with diabetes to
      decrease their risk for coronary artery disease.

PMID- 11301563
TI  - Clinical pharmacokinetics and pharmacodynamics of a new squalene synthase
      inhibitor, BMS-188494, in healthy volunteers.
AB  - A double-blind, placebo-controlled, parallel-group, ascending, multiple-dose
      study was completed in 45 healthy male volunteers to assess the maximum tolerated
      dose, pharmacokinetics, and pharmacodynamics of BMS-187745, a squalene synthase
      inhibitor, administered as multiple oral doses of its prodrug BMS-188494.
      Participants received a daily oral dose of 10 mg for 2 weeks, or a daily oral
      dose of 25, 50, 100, or 200 mg for 4 weeks. The absorption rate constant (ka) and
      bioavailability (F) values were estimated by fitting the plasma BMS-187745
      concentration-time data to a biexponential function with a first-order ka. Values
      for F were similar for all five dose levels, and thus were independent of dose.
      The ka values also were similar for all dose groups except the 50-mg group, for
      which ka values were somewhat higher. The change in urinary excretion rate of
      farnesyl pyrophosphate metabolite (dioic acid) was determined to be a
      pharmacodynamic measure. There was no significant change in dioic acid excretion
      at doses of less than 100 mg given for 4 weeks. An indirect pharmacodynamic
      response model with threshold concentration (CT) and based on inhibition of
      squalene synthase was proposed to describe the effect versus time data. The
      pharmacodynamic data from all dose levels were fitted simultaneously to the
      proposed model and the fitted parameters estimated as CT = 3.9 micrograms/mL,
      kout = 0.47 hr-1, IC50 = 4.1 micrograms/mL, and Imax = 1.0. The proposed indirect
      response model requiring a threshold concentration provides a useful means of
      quantitating responses for a new type of therapeutic agent.

PMID- 11301564
TI  - Absolute bioavailability and dose proportionality of oral ganciclovir after
      ascending multiple doses in human immunodeficiency virus (HIV)-positive patients.
AB  - This study was designed to determine the bioavailability and dose linearity and
      proportionality of ganciclovir after multiple oral administrations of 3,000 mg to
      6,000 mg per day. In an open-label, randomized, four-treatment crossover design,
      24 patients seropositive for human immunodeficiency virus (HIV) and
      cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir
      1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg
      three times a day and a single 5-mg/kg intravenous infusion (over 1 hour) of
      ganciclovir. Blood samples for pharmacokinetic determinations were obtained on
      day 3 of each oral regimen and on the day of the intravenous infusion over a 24
      hour time interval. Mean steady-state average serum concentrations of ganciclovir
      were 0.54, 0.79, and 0.99 microgram/mL, respectively, with the 3, 4, and 6 g/day
      oral regimens. The steady-state area under the concentration-time curve (AUC0-24)
      for the 6,000 mg/day oral regimen approached that of the single-dose intravenous
      regimen. There was a proportional increase in AUC0-24 between the 3 and 4 g/day
      dosage regimens, but not between the 4 and 6 g/day regimens. This suggests
      nonlinear absorption of ganciclovir at higher dosages, although the departure
      from proportionality was less than 11%.

PMID- 11301565
TI  - Pharmacodynamics and pharmacokinetics of a single oral dose of nitrazepam in
      healthy volunteers: an interethnic comparative study between Japanese and
      European volunteers.
AB  - Potential interethnic differences in drug disposition and effects between
      Japanese and white subjects hamper the registration in Japan of medications
      already used in Western countries. This double-blind, placebo-controlled,
      crossover study was conducted to compare the pharmacodynamics and
      pharmacokinetics of a single oral dose of nitrazepam (5 mg) in age- and sex
      matched Japanese (n = 8) and white (n = 8) healthy volunteers. The study was
      performed in centers in Japan and the Netherlands using the same methods and
      study design. Subjects were individually matched for gender, age, and body
      stature. Drug effects were measured by means of saccadic and smooth pursuit eye
      movements and visual analog lines obtained from the scales of Bond and Lader.
      There were no pharmacokinetic differences between the Japanese and white
      subjects. Clearance of nitrazepam was 0.91 +/- 0.165 mL/min/kg and 1.17 +/- 0.492
      mL/min/kg, and half-life (t1/2) was 22.1 +/- 4.96 hours and 21.5 +/- 7.51 hours
      for the Japanese and European groups, respectively. Pharmacokinetic parameters
      showed no significant correlation with age, height, or weight. The average time
      effect curves for the different parameters were comparable between groups.
      Compared with placebo, both groups showed similar significant reductions in
      average peak velocity and increases in saccadic inaccuracy and reaction time.
      Visual analog scores showed clear sedation in the white subjects, but
      insignificant effects in the Japanese subjects. Smooth pursuit did not change
      significantly in either group. Slope and intercept of the concentration-effect
      relationships for saccadic peak velocity showed considerable intersubject
      variability, but no clear differences between groups. The pharmacokinetics and
      pharmacodynamics of nitrazepam were similar in matched healthy Japanese and white
      subjects. Interethnic comparative studies are feasible, and provide meaningful
      information about potential racial differences in disposition and action of
      drugs. Such studies can form a rational basis for comparative clinical trials.

PMID- 11301566
TI  - Preliminary evaluation of progestins as inducers of cytochrome P450 3A4 activity
      in postmenopausal women.
AB  - The effects of intramuscularly and orally administered medroxyprogesterone
      acetate on cytochrome P450 3A4 (CYP3A4) activity were investigated in twelve
      postmenopausal women in a randomized, crossover study. Unbound prednisolone
      clearance and the erythromycin breath test were used as markers of CYP3A4
      activity. After 2 months of intramuscular progestin therapy, unbound prednisolone
      clearance increased by 25% in five of six subjects. Similarly, after
      intramuscular progestin therapy, results from the erythromycin breath test showed
      a 23% mean increase in CYP3A4 activity. In contrast, 2 months of oral progestin
      therapy had no effect on prednisolone pharmacokinetics or erythromycin
      metabolism. These results suggest that parenterally but not orally administered
      progestins may induce or activate the CYP3A4 enzyme system, leading to an
      increased metabolism of many CYP3A4 substrates.

PMID- 11301567
TI  - Laboratory values and vital signs in male smokers and nonsmokers in phase I
      trials: a retrospective comparison.
AB  - In a retrospective analysis of 13 phase I multiple-dose trials, clinical data
      from 100 volunteers who received placebo were investigated for differences in
      routine safety laboratory parameters and vital signs between smokers and
      nonsmokers. Of the 100 subjects, 47 were classified as smokers (cigarettes only)
      and 53 were classified as nonsmokers. Objectives of the analysis were to offer a
      basis for decision whether certain deviations of laboratory values or vital signs
      might be related to smoking rather than to a study drug or some external
      influence, and to explore whether smokers tend to present changes in laboratory
      values or vital signs during a trial that are different from changes that occur
      in nonsmokers. Regarding baseline values, which were defined as the mean of
      values at screening and the first day of the in-house stay, clinically and
      statistically significant differences between smokers and nonsmokers were found
      for total leukocytes and triglycerides (mean greater for smokers than
      nonsmokers), and total bilirubin (mean greater for nonsmokers than smokers).
      Comparison of changes during the study in smokers and nonsmokers showed a
      statistically and clinically significant difference only for triglyceride levels.
      Smokers had a slight decrease in triglyceride levels, whereas nonsmokers showed a
      marked increase in the respective values during the trials. Prospective studies
      with sufficiently large sample sizes are required to confirm the results of this
      retrospective analysis on a wider basis, and to possibly achieve significance for
      further differences between smokers and nonsmokers.

PMID- 11301568
TI  - Randomized, double-blind, placebo-controlled study of the safety and efficacy of
      vitamin B complex in the treatment of nocturnal leg cramps in elderly patients
      with hypertension.
AB  - Nocturnal leg cramps is a common and troublesome problem in elderly individuals,
      and their etiology is unknown. Treatment with quinine is a common practice, but
      the effectiveness of the drug is doubtful and adverse drug effects are common.
      This randomized, double-blind, placebo-controlled study was conducted to evaluate
      the safety and efficacy of vitamin B complex capsules (fursulthiamine 50 mg,
      hydroxocobalamin 250 micrograms, pyridoxal phosphate 30 mg, and riboflavin 5 mg)
      in 28 elderly patients with hypertension who had severe nocturnal leg cramps that
      disturbed their sleep. Self-reported ratings of leg cramp frequency, duration,
      and intensity were used to evaluate severity of nocturnal leg cramps. Both the
      patients taking vitamin B capsules (n = 14) and those taking placebo (n = 14)
      received medications three times daily, and were examined regularly at 2-week
      intervals for 3 months. After 3 months, 86% of the patients taking vitamin B had
      prominent remission of leg cramps, whereas those taking placebo had no
      significant difference from baseline. Treatment with vitamin B complex
      significantly reduced the frequency, intensity, and duration of nocturnal leg
      cramps. Because quinine is not without potential for side effects, and vitamin B
      complex is a relatively safe and effective alternative, clinicians should
      reconsider the treatment of choice for nocturnal leg cramps.

PMID- 11301569
TI  - Onset and duration of analgesia for low-dose ketoprofen in the treatment of
      postoperative dental pain.
AB  - The objective of this single dose, double-blind study was to determine the
      relative analgesic efficacy of low-dose ketoprofen (6.25 mg, 12.5 mg, and 25 mg)
      compared with ibuprofen (200 mg) and placebo in 175 patients with moderate to
      severe postoperative pain secondary to extraction of impacted third molars.
      Analgesia was measured during the 6-hour period after administration based on
      onset of relief, hourly and summary variables, and duration of treatment effect.
      All active treatments were significantly more effective than placebo for many
      hourly measures and for the summary measures sum of pain intensity differences
      (SPID), sum of hourly pain relief values (TOTPAR), time to peak pain relief, and
      patient global assessment of study medication. The three ketoprofen doses were
      significantly more effective than placebo beginning at 30 minutes, whereas
      ibuprofen was significantly better than placebo beginning at 1 hour. A dose
      response relationship was observed for ketoprofen, with the two higher doses
      providing significantly greater analgesia than the lower dose. However, a plateau
      effect was seen between the 12.5-mg and 25-mg dose levels. A significantly
      greater proportion of patients treated with each of the active treatments
      (ranging from 0.83 to 0.88) reported onset of relief compared with placebo
      (0.20). The distribution functions of onset of relief differed significantly
      among treatments, with ketoprofen 12.5 mg and 25 mg having a faster onset than
      ibuprofen 200 mg and ketoprofen 6.25 mg. The duration of effect was generally
      shorter for ketoprofen than for ibuprofen, and these difference were significant.
      This study provides evidence that at the dose levels of 12.5 mg and 25 mg,
      ketoprofen is an effective analgesic in providing relief of postoperative dental
      pain. Ketoprofen 12.5 mg and 25 mg provide significantly greater relief in the
      earlier time period, with a faster onset and shorter duration of effect than
      ibuprofen 200 mg. The two higher doses of ketoprofen provided similar analgesia,
      and no additional benefit was obtained by increasing the dose of ketoprofen to 25
      mg. Therefore, we conclude that ketoprofen 12.5 mg is an appropriate dose for
      over-the-counter use.

PMID- 11301570
TI  - A theory of implicit and explicit knowledge.
AB  - The implicit-explicit distinction is applied to knowledge representations.
      Knowledge is taken to be an attitude towards a proposition which is true. The
      proposition itself predicates a property to some entity. A number of ways in
      which knowledge can be implicit or explicit emerge. If a higher aspect is known
      explicitly then each lower one must also be known explicitly. This partial
      hierarchy reduces the number of ways in which knowledge can be explicit. In the
      most important type of implicit knowledge, representations merely reflect the
      property of objects or events without predicating them of any particular entity.
      The clearest cases of explicit knowledge of a fact are representations of one's
      own attitude of knowing that fact. These distinctions are discussed in their
      relationship to similar distinctions such as procedural-declarative, conscious
      unconscious, verbalizable-nonverbalizable, direct-indirect tests, and automatic
      voluntary control. This is followed by an outline of how these distinctions can
      be used to integrate and relate the often divergent uses of the implicit-explicit
      distinction in different research areas. We illustrate this for visual
      perception, memory, cognitive development, and artificial grammar learning.

PMID- 11301571
TI  - A neuron doctrine in the philosophy of neuroscience.
AB  - Many neuroscientists and philosophers endorse a view about the explanatory reach
      of neuroscience (which we will call the neuron doctrine) to the effect that the
      framework for understanding the mind will be developed by neuroscience; or, as we
      will put it, that a successful theory of the mind will be solely neuroscientific.
      It is a consequence of this view that the sciences of the mind that cannot be
      expressed by means of neuroscientific concepts alone count as indirect sciences
      that will be discarded as neuroscience matures. This consequence is what makes
      the doctrine substantive, indeed, radical. We ask, first, what the neuron
      doctrine means and, second, whether it is true. In answer to the first question,
      we distinguish two versions of the doctrine. One version, the trivial neuron
      doctrine, turns out to be uncontroversial but unsubstantive because it fails to
      have the consequence that the nonneuroscientific sciences of the mind will
      eventually be discarded. A second version, the radical neuron doctrine, does have
      this consequence, but, unlike the first doctrine, is highly controversial. We
      argue that the neuron doctrine appears to be both substantive and uncontroversial
      only as a result of a conflation of these two versions. We then consider whether
      the radical doctrine is true. We present and evaluate three arguments for it,
      based either on general scientific and philosophical considerations or on the
      details of neuroscience itself, arguing that all three fail. We conclude that the
      evidence fails to support the radical neuron doctrine.

PMID- 11301572
TI  - Precis of "Lifelines: biology, freedom, determinism".
AB  - There are many ways of describing and explaining the properties of living
      systems; causal, functional, and reductive accounts are necessary but no one
      account has primacy. The history of biology as a discipline has given excessive
      authority to reductionism, which collapses higher level accounts, such as social
      or behavioural ones, into molecular ones. Such reductionism becomes crudely
      ideological when applied to the human condition, with its claims for genes "for"
      everything from sexual orientation to compulsive shopping. The current enthusiasm
      for genetics and ultra-Darwinist accounts, with their selfish-gene metaphors for
      living processes, misunderstand both the phenomena of development and the
      interactive role that DNA and the fluid genome play in the cellular orchestra.
      DNA is not a blueprint, and the four dimensions of life (three of space, one of
      time) cannot be read off from its one-dimensional strand. Both developmental and
      evolutionary processes are more than merely instructive or selective; the
      organism constructs itself, a process known as autopoiesis, through a lifeline
      trajectory. Because organisms are thermodynamically open systems, living
      processes are homeodynamic, not homeostatic. The self-organising membrane-bound
      and energy-utilising metabolic web of the cell must have evolved prior to
      socalled naked replicators. Evolution is constrained by physics, chemistry, and
      structure; not all change is powered by natural selection, and not all phenotypes
      are adaptive. Finally, therefore, living processes are radically indeterminate;
      like all other living organisms, but to an even greater degree, we make our own
      future, though in circumstances not of our own choosing.

PMID- 11301573
TI  - Color, consciousness, and the isomorphism constraint.
AB  - The relations among consciousness, brain behavior, and scientific explanation are
      explored in the domain of color perception. Current scientific knowledge about
      color similarity, color composition, dimensional structure, unique colors, and
      color categories is used to assess Locke's "inverted spectrum argument" about the
      undetectability of color transformations. A symmetry analysis of color space
      shows that the literal interpretation of this argument--reversing the experience
      of a rainbow--would not work. Three other color to color transformations might
      work, however, depending on the relevance of certain color categories. The
      approach is then generalized to examine behavioral detection of arbitrary
      differences in color experiences, leading to the formulation of a principled
      distinction, called the "isomorphism constraint," between what can and cannot be
      determined about the nature of color experience by objective behavioral means.
      Finally, the prospects for achieving a biologically based explanation of color
      experience below the level of isomorphism are considered in light of the
      limitations of behavioral methods. Within-subject designs using biological
      interventions hold the greatest promise for scientific progress on consciousness,
      but objective knowledge of another person's experience appears impossible. The
      implications of these arguments for functionalism are discussed.

PMID- 11301574
TI  - Lexical entries and rules of language: a multidisciplinary study of German
      inflection.
AB  - Following much work in linguistic theory, it is hypothesized that the language
      faculty has a modular structure and consists of two basic components, a lexicon
      of (structured) entries and a computational system of combinatorial operations to
      form larger linguistic expressions from lexical entries. This target article
      provides evidence for the dual nature of the language faculty by describing
      recent results of a multidisciplinary investigation of German inflection. We have
      examined: (1) its linguistic representation, focussing on noun plurals and verb
      inflection (participles), (2) processes involved in the way adults produce and
      comprehend inflected words, (3) brain potentials generated during the processing
      of inflected words, and (4) the way children acquire and use inflection. It will
      be shown that the evidence from all these sources converges and supports the
      distinction between lexical entries and combinatorial operations. Our
      experimental results indicate that adults have access to two distinct processing
      routes, one accessing (irregularly) inflected entries from the mental lexicon and
      another involving morphological decomposition of (regularly) inflected words into
      stem + affix representations. These two processing routes correspond to the dual
      structure of the linguistic system. Results from event-related potentials confirm
      this linguistic distinction at the level of brain structures. In children's
      language, we have also found these two processes to be clearly dissociated;
      regular and irregular inflection are used under different circumstances, and the
      constraints under which children apply them are identical to those of the adult
      linguistic system. Our findings will be explained in terms of a linguistic model
      that maintains the distinction between the lexicon and the computational system
      but replaces the traditional view of the lexicon as a simple list of
      idiosyncrasies with the notion of internally structured lexical representations.

PMID- 11301575
TI  - Merging information in speech recognition: feedback is never necessary.
AB  - Top-down feedback does not benefit speech recognition; on the contrary, it can
      hinder it. No experimental data imply that feedback loops are required for speech
      recognition. Feedback is accordingly unnecessary and spoken word recognition is
      modular. To defend this thesis, we analyse lexical involvement in phonemic
      decision making. TRACE (McClelland & Elman 1986), a model with feedback from the
      lexicon to prelexical processes, is unable to account for all the available data
      on phonemic decision making. The modular Race model (Cutler & Norris 1979) is
      likewise challenged by some recent results, however. We therefore present a new
      modular model of phonemic decision making, the Merge model. In Merge, information
      flows from prelexical processes to the lexicon without feedback. Because phonemic
      decisions are based on the merging of prelexical and lexical information, Merge
      correctly predicts lexical involvement in phonemic decisions in both words and
      nonwords. Computer simulations show how Merge is able to account for the data
      through a process of competition between lexical hypotheses. We discuss the issue
      of feedback in other areas of language processing and conclude that modular
      models are particularly well suited to the problems and constraints of speech
      recognition.

PMID- 11301576
TI  - Toward a quantitative description of large-scale neocortical dynamic function and
      EEG.
AB  - A general conceptual framework for large-scale neocortical dynamics based on data
      from many laboratories is applied to a variety of experimental designs, spatial
      scales, and brain states. Partly distinct, but interacting local processes (e.g.,
      neural networks) arise from functional segregation. Global processes arise from
      functional integration and can facilitate (top down) synchronous activity in
      remote cell groups that function simultaneously at several different spatial
      scales. Simultaneous local processes may help drive (bottom up) macroscopic
      global dynamics observed with electroencephalography (EEG) or
      magnetoencephalography (MEG). A local/global dynamic theory that is consistent
      with EEG data and the proposed conceptual framework is outlined. This theory is
      neutral about properties of neural networks embedded in macroscopic fields, but
      its global component makes several qualitative and semiquantitative predictions
      about EEG measures of traveling and standing wave phenomena. A more general
      "metatheory" suggests what large-scale quantitative theories of neocortical
      dynamics may be like when more accurate treatment of local and nonlinear effects
      is achieved. The theory describes the dynamics of excitatory and inhibitory
      synaptic action fields. EEG and MEG provide large-scale estimates of modulation
      of these synaptic fields around background levels. Brain states are determined by
      neuromodulatory control parameters. Purely local states are dominated by local
      feedback gains and rise and decay times of postsynaptic potentials. Dominant
      local frequencies vary with brain region. Other states are purely global, with
      moderate to high coherence over large distances. Multiple global mode frequencies
      arise from a combination of delays in corticocortical axons and neocortical
      boundary conditions. Global frequencies are identical in all cortical regions,
      but most states involve dynamic interactions between local networks and the
      global system. EEG frequencies may involve a "matching" of local resonant
      frequencies with one or more of the many, closely spaced global frequencies.

PMID- 11301577
TI  - Precis of The brain and emotion.
AB  - The topics treated in The brain and emotion include the definition, nature, and
      functions of emotion (Ch. 3); the neural bases of emotion (Ch. 4); reward,
      punishment, and emotion in brain design (Ch. 10); a theory of consciousness and
      its application to understanding emotion and pleasure (Ch. 9); and neural
      networks and emotion-related learning (Appendix). The approach is that emotions
      can be considered as states elicited by reinforcers (rewards and punishers). This
      approach helps with understanding the functions of emotion, with classifying
      different emotions, and in understanding what information-processing systems in
      the brain are involved in emotion, and how they are involved. The hypothesis is
      developed that brains are designed around reward- and punishment-evaluation
      systems, because this is the way that genes can build a complex system that will
      produce appropriate but flexible behavior to increase fitness (Ch. 10). By
      specifying goals rather than particular behavioral patterns of responses, genes
      leave much more open the possible behavioral strategies that might be required to
      increase fitness. The importance of reward and punishment systems in brain design
      also provides a basis for understanding the brain mechanisms of motivation, as
      described in Chapters 2 for appetite and feeding, 5 for brain-stimulation reward,
      6 for addiction, 7 for thirst, and 8 for sexual behavior.

PMID- 11301578
TI  - Pavlovian feed-forward mechanisms in the control of social behavior.
AB  - The conceptual and investigative tools for the analysis of social behavior can be
      expanded by integrating biological theory, control systems theory, and Pavlovian
      conditioning. Biological theory has focused on the costs and benefits of social
      behavior from ecological and evolutionary perspectives. In contrast, control
      systems theory is concerned with how machines achieve a particular goal or
      purpose. The accurate operation of a system often requires feed-forward
      mechanisms that adjust system performance in anticipation of future inputs.
      Pavlovian conditioning is ideally suited to subserve this function in behavioral
      systems. Pavlovian mechanisms have been demonstrated in various aspects of sexual
      behavior, maternal lactation, and infant suckling. Pavlovian conditioning of
      agonistic behavior has been also reported, and Pavlovian processes may likewise
      be involved in social play and social grooming. Several further lines of evidence
      indicate that Pavlovian conditioning can increase the efficiency and
      effectiveness of social interactions, thereby improving their cost/benefit ratio.
      We extend Pavlovian concepts beyond the traditional domain of discrete secretory
      and other physiological reflexes to complex real-world behavioral interactions
      and apply abstract laboratory analyses of the mechanisms of associative learning
      to the daily challenges animals face as they interact with one another in their
      natural environments.

PMID- 11301579
TI  - Voluntary CHF pathways cut costs, boost outcomes.

PMID- 11301580
TI  - Predict the future with claims data plus pharmacy information.
AB  - The technology and know-how are out there to give adminstrators a reasonable
      guess at future clinical costs for a given population. All you have to do is ask.

PMID- 11301581
TI  - New strategies available for fast chest pain triaging.
AB  - The credit goes to new technology and a changing relationship among hospital
      based physicians and cardiologists. Sophisticated triaging can save millions, if
      not billions, annually, and improve the quality of care of chest pain patients.

PMID- 11301582
TI  - Telephonic DM approach to maternity management produces solid returns.
AB  - Maternity management can be effective and inexpensive. A Richmond, VA-based
      program is documenting savings for both low- and high-risk pregnancies compared
      to cases in which care is not managed.

PMID- 11301583
TI  - Virginia hospitals join to create data repository for cardiac surgery.
AB  - Initiative shares best practices among 17 hospitals and 10 surgery groups.

PMID- 11301584
TI  - Clinicians pay closer attention to malnutrition in elderly.

PMID- 11301585
TI  - Highlights of human toxocariasis.
AB  - Human toxocariasis is a helminthozoonosis due to the migration of Toxocara
      species larvae through human organism. Humans become infected by ingesting either
      embryonated eggs from soil (geophagia, pica), dirty hands or raw vegetables, or
      larvae from undercooked giblets. The diagnosis relies upon sensitive
      immunological methods (ELISA or western-blot) which use Toxocara excretory
      secretory antigens. Seroprevalence is high in developed countries, especially in
      rural areas, and also in some tropical islands. The clinical spectrum of the
      disease comprises four syndromes, namely visceral larva migrans, ocular larva
      migrans, and the more recently recognized "common" (in adults) and "covert" (in
      children) pictures. Therapy of ocular toxocariasis is primarily based upon
      corticosteroids use, when visceral larva migrans and few cases of common or
      covert toxocariasis can be treated by anthelmintics whose the most efficient
      appeared to be diethylcarbamazine. When diagnosed, all of these syndromes require
      thorough prevention of recontamination (especially by deworming pets) and
      sanitary education.

PMID- 11301586
TI  - Localization of cytoskeletal proteins in Pneumocystis carinii by immuno-electron
      microscopy.
AB  - Pneumocystis carinii causes serious pulmonary infection in immunosuppressed
      patients. This study was undertaken to observe the cytoskeletal proteins of P.
      carinii by immuno-electron microscopy. P. carinii infection was experimentally
      induced by immunosuppression of Sprague-Dawley rats for seven weeks, and their
      lungs were used for the observations of this study. The gold particles localized
      actin, tropomyosin, and tubulin. The actin was irregularly scattered in the
      cytoplasm of the trophic forms but was much more concentrated in the inner space
      of the cell wall of the cystic forms called the inner electron-lucent layer. No
      significant amount of tropomyosin was observed in either trophic forms or cystic
      forms. The tubulin was distributed along the peripheral cytoplasm and filopodia
      of both the trophic and cystic forms rather than in the inner side of the
      cytoplasm. Particularly, in the cystic forms, the amount of tubulin was increased
      and located mainly in the inner electron-lucent layer of the cell wall where the
      actin was concentrated as well. The results of this study showed that the cell
      wall of P. carinii cystic forms is a structure whose inner side is rich in actin
      and tubulin. The location of the actin and tubulin in P. carinii suggests that
      the main role of these proteins is an involvement in the protection of cystic
      forms from the outside environment by maintaining rigidity of the cystic forms.

PMID- 11301587
TI  - A nationwide survey of the prevalence of human Gymnophalloides seoi infection on
      western and southern coastal islands in the Republic of Korea.
AB  - A nationwide survey was performed to know the distribution and prevalence of
      human Gymnophalloides seoi infection on western and southern coastal islands in
      the Republic of Korea. A total of 4,178 fecal specimens were collected from
      residents on 45 (24 western and 21 southern) islands, and examined by Kato-Katz
      and formalin-ether sedimentation techniques. Eggs of G. seoi were detected from
      160 (3.8%) people living on 22 (13 western and 9 southern) islands. The
      prevalence varied by the location of islands; higher on western islands than on
      southern islands. The highest prevalence was found on Amtaedo (25.3%), followed
      by Cheungdo (25.0%), and Anchwado (20.9%) (Shinan-gun). A little lower prevalence
      was observed on Munyodo (13.3%), Shinshido (12.9%), and Sonyudo (10.3%) (Kunsan
      shi). Of the remaining islands, the regions showing the prevalence greater than
      5% included Kohado, Dallido (Mokpo-shi), Pyeongildo, Kogumdo (Wando-gun), and
      Keogumdo (Kohung-gun). A strong age predilection was noted (p < 0.05); 95% of the
      infected people were over 40 years old. Females showed a little higher prevalence
      than males. The results indicate that human G. seoi infection is more widely
      distributed than previously considered. Nine of 11 islands (excluding the 2 known
      areas Munyodo and Sunyudo) that showed greater prevalence than 5% are regarded as
      new endemic foci of G. seoi.

PMID- 11301588
TI  - Intestinal histopathology and in situ postures of Gymnophalloides seoi in
      experimentally infected mice.
AB  - The intestinal histopathology and in situ postures of Gymnophalloides seoi
      (Digenea: Gymnophallidae) were studied using C3H/HeN and C57BL/6 mice as
      experimental hosts; the effects of immunosuppression were also observed. The
      metacercariae isolated from naturally infected oysters, 300 or 1,000 in number,
      were infected orally to each mouse, and the mice were killed at days 3-21 post
      infection (PI). In immunocompetent (IC) mice, only a small number of flukes were
      found in the mucosa of the duodenum and jejunum during days 3-7 PI, with their
      large oral suckers pinching and sucking the root of villi. The intestinal mucosa
      showed mild villous atrophy, crypt hyperplasia, and inflammations in the villous
      stroma and crypt, with remarkable goblet cell hyperplasia. These mucosal changes
      were almost restored after days 14-21 PI. In immunosuppressed (IS) mice,
      displacement as well as complete loss of villi adjacent to the flukes was
      frequently encountered, otherwise the histopathology was generally mild, with
      minimal goblet cell hyperplasia. In these mice, numerous flukes were found, and
      it seemed that they were actively moving and rotating in situ. Several flukes
      were found to have invaded into the submucosa, almost facing the serosa. These
      results indicate that in IC mice the intestinal histopathology caused by G. seoi
      is generally mild, and the flukes do not penetrate beyond the mucosa, however, in
      IS mice, the flukes can cause severe destruction of neighboring villi, and some
      of them invade into the submucosa.

PMID- 11301589
TI  - PCR-RFLP patterns of four isolates of Trichinella for rDNA ITS1 region.
AB  - We have studied the genetic differences among four isolates of Trichinella
      including a new strain of Trichinella spiralis (ISS 623) recently found from a
      human case who took a badger in Korea. Because they have a different host origin
      and came from geographically separated regions, we supposed the genetic pattern
      of the isolates might be different as had been previously reported. It was
      analysed by PCR-RFLP analysis of the rDNA repeat that can readily distinguish a
      species or strain from others. Isolated genomic DNA of each isolate of
      Trichinella larvae was amplified with ITS1 specific primers and digested with
      restriction endonucleases. The PCR product of ITS1 was confirmed using Southern
      blot analysis to be a 910 bp fragment. The restriction fragments of each isolate
      had variable patterns when it was digested with Rsa 1 only. According to the RFLP
      patterns, the estimated genetic divergence between each isolate was different. In
      conclusion, four isolates of Trichinella including a new strain of T. spiralis
      obtained from a Korean patient may have genetic differences in the ITS1 region
      and the Shanghai isolate was genetically more similar to the Japanese unknown
      isolate than others in the ITS1 region.

PMID- 11301590
TI  - Detection and characterization of excretory/secretory proteins from Toxoplasma
      gondii by monoclonal antibodies.
AB  - Excretory/secretory proteins (ESP) from Toxoplasma gondii were analyzed to define
      the function in the penetration process into host cells. Whole ESP obtained at 37
      degrees C were composed of 15 bands with molecular mass of 110, 97, 86, 80, 70,
      60, 54, 42, 40, 36, 30, 28, 26, 22, and 19 kDa. Five ESP of 86, 80, 42, 36, and
      28 kDa were reacted with monoclonal antibodies (mAb), named as Tg386 (microneme),
      Tg485 (surface membrane), Tg786 (rhoptry), Tg378, and Tg556 (both dense
      granules), respectively. The ESP was released by a temperature-dependent/
      independent manner and all at once whenever ready to pour out except Tg786. Each
      ESP was not exhausted within the parasite but the amount was limited. Tg786 was
      released continuously with increment, whereas Tg378 and Tg556 were ceased to
      release after 3 and 4 hr. Dense granular Tg378 and Tg556 were released
      spontaneously and constitutively before the entry into host cells also. The entry
      of T. gondii was inhibited by all the mAbs differentially. And the parasite
      deprived of ESP was inhibited to enter exponentially up to 90.1%. It is suggested
      that ESP play an essential function to provide appropriate environment for the
      entry of the parasite into host cells.

PMID- 11301591
TI  - Molecular cloning and characterization of an antigenic protein with a repeating
      region from Clonorchis sinensis.
AB  - In the course of immunoscreening of Clonorchis sinensis cDNA library, a cDNA
      CsRP12 containing a tandem repeat was isolated. The cDNA CsRP12 encodes two
      putative peptides of open reading frames (ORFs) 1 and 2 (CsRP12-1 and -2). The
      repetitive region is composed of 15 repeats of 10 amino acids. Of the two
      putative peptides, CsRP12-1 was proline-rich and found to have homologues in
      several organisms. Recombinant proteins of the putative peptides were bacterially
      produced and purified by an affinity chromatography. Recombinant CsRP12-1 protein
      was recognized by sera of clonorchiasis patients and experimental rabbits, but
      recombinant CsRP12-2 was not. One of the putative peptide, CsRP12-1, is
      designated CsPRA, proline-rich antigen of C. sinensis. Both the C-termini of
      CsRP12-1 and -2 were bacterially produced and analysed to show no antigenicity.
      Recombinant CsPRA protein showed high sensitivity and specificity. In
      experimental rabbits, IgG antibodies to CsPRA was produced between 4 and 8 weeks
      after the infection and decreased thereafter over one year. These results
      indicate that CsPRA is equivalent to a natural protein and a useful antigenic
      protein for serodiagnosis of human clonorchiasis.

PMID- 11301592
TI  - Toxoplasma gondii: ultrastructural localization of specific antigens and
      inhibition of intracellular multiplication by monoclonal antibodies.
AB  - This experiment was focused on the characterization of anti-Toxoplasma monoclonal
      antibodies (mAbs) and the effect of mAbs on the parasite invasion of mouse
      peritoneal macrophages. Twenty eight mAbs including M110, M556, R7A6 and M621
      were characterized by Ab titer, immunoglobulin isotyping and western blot
      pattern. Antibody titer (optical density) of 4 mAbs, M110, M556, R7A6 and M621,
      were 0.53, 0.67, 0.45 and 0.39 (normal mouse serum; 0.19) with the same IgG1
      isotypes shown by Enzyme-linked immunosorbent assay (ELISA). Western blot
      analysis showed that M110, M556, R7A6 and M621 reacted with the 33 kDa (p30), 31
      kDa (p28), 43 kDa and 36 kDa protein. Immunogold labelling of mAbs M110, M556,
      R7A6 and M621 reacted with the surface membrane, dense granules and
      parasitophorous vacuolar membrane (PVM), rhoptries and cytoplasm of tachyzoite,
      respectively. For in vitro assay, preincubation of tachyzoites with four mAbs,
      M110, M556, R7A6 and M621 resulted in the decrease of the number of infected
      macrophages (p < 0.05) and the suppression of parasite multiplication at 18 h
      post-infection. Four monoclonal antibodies including M110 (SAG1) were found to
      have an important role in the inhibition of macrophage invasion and T. gondii
      multiplication in vitro, and these mAbs may be suitable for vaccine candidates,
      diagnostic kit and for chemotherapy.

PMID- 11301593
TI  - Two imported cases of cutaneous larva migrans.
AB  - Cutaneous larva migrans (CLM) is a rare serpiginous cutaneous eruption caused by
      accidental penetration and migration in the skin with infective larvae of
      nematode that normally do not have the human as their host. Although CLM has a
      worldwide distribution, the infection is most frequent in warmer climates. More
      recently, they have been increasingly imported from the tropics or subtropics by
      travelers. We experienced two patients who had pruritic serpiginous linear
      eruption in their skin for a few weeks after traveling to the endemic areas
      (Brazil and Thailand, respectively). After the treatment with albendazole, the
      skin lesions resolved with post-inflammatory hyperpigmentation. We report herein
      two cases of cutaneous larva migrans successfully treated with albendazole.

PMID- 11301594
TI  - The one-to-four rule and paralogues of sex-determining genes.
AB  - Because of two successive rounds of tetraploidization at their inception, the
      vertebrates contain four times more protein-coding genes in their genome than the
      invertebrates: 60,000 vs. 15,000. Consequently, each invertebrate gene has been
      amplified to the maximum of four paralogous genes in vertebrates: the one-to-four
      rule. When this rule is applied to genes pertinent to gonadal development and
      differentiation, the following emerged: (i) Two closely related zinc-finger
      transcription factor genes in invertebrates have been amplified to two paralogous
      groups in vertebrates. One consisted of EGR1, EGR2, EGR3 and EGR4, whereas the
      only known paralogue of the other is WT1, which controls the developmental fate
      of the entire nephric system, and therefore of gonads. Interestingly, EGR1 and
      WT1 act as antagonists of each other in nephroblastic cells. (ii) SF-1, which
      controls the fate of two steroid hormone-producing organs, adrenals and gonads,
      is descended from the invertebrate Ftz-F1 gene, and its only known paralogue is
      GCNF-1. (iii) The Y-linked SRY, the mammalian testis-determining gene, is a
      paralogue neither of SOX3 (SRX) nor of SOX9. Its ancient origin suggests that SRY
      once became extinct in earlier vertebrates, only to revive itself in the
      mammalian ancestor. (iv) Inasmuch as four paralogues of one invertebrate nuclear
      receptor gene have differentiated to receptors of androgen, mineralocorticoid,
      glucocorticoid and progesterone, there should at most be four paralogous estrogen
      receptor genes in the vertebrate genome. It is likely that one of them plays a
      pivotal role in the estrogen-dependent sex-determining mechanism so commonly
      found among reptiles, amphibians and fish.

PMID- 11301595
TI  - Genes essential for early events in gonadal development.
AB  - The acquisition of a sexually dimorphic phenotype is a critical event in
      mammalian development. The basic underlying principle of sexual development is
      that genetic sex--determined at fertilization by the presence or absence of the Y
      chromosome--directs the embryonic gonads to differentiate into either testes or
      ovaries. Thereafter, hormones produced by the testes direct the developmental
      program that leads to male sexual differentiation. In the absence of testicular
      hormones, the female pathway of sexual differentiation occurs. Recent studies
      have defined key roles in gonadal development for two transcription factors:
      Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF-1). After
      presenting a brief overview of gonadal development and sexual differentiation,
      this chapter reviews the studies that led to the isolation and characterization
      of WT1 and SF-1, and then discusses how interactions between these two genes may
      mediate their key roles in a common developmental pathway.

PMID- 11301596
TI  - Temperature-dependent sex determination and gonadal differentiation in reptiles.
AB  - In many reptile species, sexual differentiation of gonads is sensitive to
      temperature (temperature-dependent sex determination, TSD) during a critical
      period of embryonic development (thermosensitive period, TSP). Experiments
      carried out with different models including turtles, crocodilians and lizards
      have demonstrated the implication of estrogens and the key role played by
      aromatase (the enzyme complex that converts androgens to estrogens) in ovary
      differentiation during TSP and in maintenance of the ovarian structure after TSP.
      In some of these experiments, the occurrence of various degrees of gonadal
      intersexuality is related to weak differences in aromatase activity, suggesting
      subtle regulations of the aromatase gene at the transcription level. Temperature
      could intervene in these regulations. Studies presently under way deal with
      cloning (cDNAs) and expression (mRNAs) of genes that have been shown, or are
      expected, to be involved in gonadal formation and/or differentiation in mammals.
      Preliminary results show that homologues of the WT1, SF1, SOX9, DAX1 and AMH
      genes exist in TSD reptiles. However, the expression patterns of these genes
      during gonadal differentiation may be different between mammals and TSD reptiles
      and also between different reptile species. How these genes could interact with
      aromatase is being examined.

PMID- 11301597
TI  - Sex chromosomes, sex-linked genes, and sex determination in the vertebrate class
      amphibia.
AB  - In this chapter the different categories of homomorphic and heteromorphic sex
      chromosomes, types of sex-determining mechanisms, known sex-linked genes, and
      data about sex-determining genes in the Amphibia have been compiled. Thorough
      cytogenetic analyses have shown that both XY/XX and ZW/ZZ sex chromosomes exist
      in the order Anura and Urodela. In some species quite unusual systems of sex
      determination have evolved (e.g. 0W-females/00-males or the co-existence of XY/XX
      and ZW/ZZ sex chromosomes within the same species). In the third order of the
      Amphibia, the Gymnophiona (or Apoda) there is still no information regarding any
      aspect of sex determination. Whereas most species of Anura and Urodela present
      undifferentiated, homomorphic sex chromosomes, there is also a considerable
      number of species in which an increasing structural complexity of the Y and W
      chromosomes exists. In various cases, the morphological differentiation of the
      sex chromosomes occurred as a result of quantitative and/or qualitative changes
      to the repetitive DNA sequences in the constitutive heterochromatin of the Y and
      W chromosomes. The greater the structural differences between the sex
      chromosomes, the lesser the extent of pairing in meiosis. No dosage compensation
      of the sex-linked genes in the somatic cells of the homogametic (XX or ZZ)
      individuals have been detected. The genes located to date on the amphibian sex
      chromosomes lead to the conclusion that there is no common ancestral or conserved
      sex-linkage group. In all amphibians, genetic sex determination (GSD) seems to
      operate, although environmental factors may influence sex determination and
      differentiation. Despite the accumulated evidence that GSD is operating in Anura
      and Urodela, there is little substantial information about how it functions.
      Although several DNA sequences homologous to the mammalian ZFY, SRY and SOX genes
      have been detected in the Anura or Urodela, none of these genes is an appropriate
      candidate to explain sex determination in these vertebrates.

PMID- 11301598
TI  - Endocrine and environmental aspects of sex differentiation in gonochoristic fish.
AB  - This paper reviews current knowledge concerning the endocrine and environmental
      regulation of gonadal sex differentiation in gonochoristic fish. In gonochoristic
      fish, although potentially active around this period, the hypothalamo-pituitary
      axis is probably not involved in triggering sex differentiation. Although
      steroids and steroidogenic enzymes are probably not the initial triggers of sex
      differentiation, new data, including molecular approaches, have confirmed that
      they are key physiological steps in the regulation of this process. Environmental
      factors can strongly influence sex differentiation in gonochoristic fish. The
      most important environmental determinant of sex would appear to be temperature.
      Interactions between environmental factors and genotype have been suggested for
      gonochoristic fish.

PMID- 11301599
TI  - Sry, Sox9 and mammalian sex determination.
AB  - Sry is the Y-chromosomal gene that acts as a trigger for male development in
      mammalian embryos. This gene encodes a high mobility group (HMG) box
      transcription factor that is known to bind to specific target sequences in DNA
      and to cause a bend in the chromatin. DNA bending appears to be part of the
      mechanism by which Sry influences transcription of genes downstream in a cascade
      of gene regulation leading to maleness, but the factors that cooperate with, and
      the direct targets of, Sry remain to be identified. One gene known to be
      downstream from Sry in this cascade in Sox9, which encodes a transcription factor
      related to Sry by the HMG box. Like Sry, mutations in Sox9 disrupt male
      development, but unlike Sry, the role of Sox9 is not limited to mammals. This
      review focuses on what is known about the two genes and their likely modes of
      action, and draws together recent data relating to how they might interconnect
      with the network of gene activity implicated in testis determination in mammals.

PMID- 11301600
TI  - DAX-1, an "antitestis" gene.
AB  - The DAX-1 gene has been involved in the dosage sensitive sex reversal (DSS)
      phenotype, a male-to-female sex-reversal syndrome due to the duplication of a
      small region of human chromosome Xp21. Dax-1 and Sry have been shown to act
      antagonistically in the mouse system, where increasing expression of the former
      leads to female development and increasing activity of the latter to male
      development. Although these data strongly implicate DAX-1 in sex determination,
      the mouse and human proteins appear to behave differently. Absence of DAX-1 is
      responsible for adrenal hypoplasia congenita, a human inherited disorder
      characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Unlike
      human patients, Dax-1-deficient XY mice have normal levels of corticotropins and
      adrenal hormones but are sterile. Dax-1-deficient females are fertile. The DAX-1
      protein, an unusual member of the nuclear hormone receptor, may act as a
      transcriptional repressor. It has been shown to both repress transcriptional
      activators by direct protein-protein interactions and to bind DNA hairpin
      structures and repress target genes.

PMID- 11301601
TI  - Sex chromosomes and sex-determining genes: insights from marsupials and
      monotremes.
AB  - Comparative studies of the genes involved in sex determination in the three
      extant classes of mammals, and other vertebrates, has allowed us to identify
      genes that are highly conserved in vertebrate sex determination and those that
      have recently evolved roles in one lineage. Analysis of the conservation and
      function of candidate sex determining genes in marsupials and monotremes has been
      crucial to our understanding of their function and positioning in a conserved
      mammalian sex-determining pathway, as well as their evolution. Here we review
      comparisons between genes in the sex-determining pathway in different
      vertebrates, and ask how these comparisons affect our views on the role of each
      gene in vertebrate sex determination.

PMID- 11301602
TI  - An overview of factors influencing sex determination and gonadal development in
      birds.
AB  - The morphological development of the embryonic gonads is very similar in birds
      and mammals, and recent evidence suggests that the genes involved in this process
      are conserved between these classes of vertebrates. The genetic mechanism by
      which sex is determined in birds remains to be elucidated, although recent
      studies have reinforced the contention that steroids may play an important role
      in the structural development of the testes and ovaries in birds. So far, few
      genes have been assigned to the avian sex chromosomes, but it is known that the Z
      and W chromosomes do not share significant homology with the mammalian X and Y
      chromosomes. The commercial importance of poultry breeding has motivated
      considerable investment in developing physical and genetic maps of the chicken
      genome. These efforts, in combination with modern molecular approaches to
      analyzing gene expression, should help to elucidate the sex-determining mechanism
      in birds in the near future.

PMID- 11301603
TI  - Genes and mechanisms in vertebrate sex determination. Introduction.

PMID- 11301604
TI  - [Children are not small adults].

PMID- 11301605
TI  - [Drug information from the producers].

PMID- 11301606
TI  - [Should the society give priority to costly diseases?].

PMID- 11301607
TI  - [Screening for anything?].

PMID- 11301608
TI  - [Urinary problems and prostate-specific antigen in a Norwegian normal
      population].
AB  - BACKGROUND: Measurements of PSA in serum is crucial in the diagnostic work-up of
      prostatic diseases. MATERIAL AND METHODS: We have studied the distribution of PSA
      values in an unselected population of 609 men, and the relation between PSA level
      and urinary symptoms, age and prostate volume. RESULTS: 87 (14%) men had a PSA
      concentration at or above the reference value of 4.0 ng/ml. Prostate cancer was
      verified in 14 (16%) of these men. The probability of having PSA equal to or
      above 4.0 ng/ml was 12 times greater for men with a prostate volume of 40 cm3 or
      less than for men with a prostate volume less than 20 cm3. Mean PSA values were
      higher in men with severe than with mild urinary symptoms, but symptoms were poor
      predictors of PSA levels. Age was not associated with an increase in PSA level
      independent of prostate volume. INTERPRETATION: Absence of urinary symptoms does
      not exclude elevated PSA values and thus not cancer. Most men with PSA equal to
      or above 10.0 ng/ml will have prostate cancer, but enlarged prostate without
      cancer can also give elevated PSA values.

PMID- 11301609
TI  - [Acid-related disease in the population of two Norwegian municipalities-
      diagnosis and drug therapy].
AB  - BACKGROUND: The introduction of acid suppressant, cytoprotective and prokinetic
      drugs represented major progress in the treatment of acid-related diseases. In
      Norway, these drugs were reimbursed by the National Insurance System (NIS) from
      1986. However, even if the distribution of the various diagnostic indications for
      prescribing were lacking, this reimbursement was stopped in 1995. The aim of this
      study was to describe prescriptions for presumed licensed diagnostic indications
      of these drugs for a defined population, and analyse them with regard to patients
      characteristics, verified (endoscopic) diagnoses, and therapeutic guidelines.
      MATERIAL AND METHODS: All prescriptions issued in 1994 to inhabitants of
      Lindesnes and Mandal Municipalities (17,105 inhabitants) were retrospectively
      retrieved from the pharmacies and the NIS. The medical records of the local
      endoscopy units and roentgen laboratories were subsequently searched for
      information on diagnostic procedures and final diagnosis leading to the
      prescriptions for these patients. RESULTS: A total number of 1,128 prescriptions
      (87,905 DDDs) were issued to 441 patients (3% of the population at risk; mean age
      63 years; 55% men), and more commonly for the elderly (for 11% of those aged 80
      years or more). Diagnostic procedures were documented for 93% of the patients
      (upper endoscopy in 404, 92%). Diagnostic indications for prescribing were reflux
      oesophagitis (48%), duodenal ulcer (24%), gastric ulcer (13%), and dyspepsia with
      normal endoscopic findings (12%). The drugs issued were H2-receptor antagonists
      (59%), proton pump inhibitors (31%), and cisapride (10%). 8% of the patients were
      long-term users of an NSAID. Of the 441 patients, drug treatment was issued to 38
      with normal endoscopic findings and to 31 patients in whom we could not document
      examination by endoscopy or X-ray. INTERPRETATION: This study supports that the
      prevalence of dyspeptic complaints calling for drug treatment increases with
      patient age. With minor exceptions we found that the prescribing practice for the
      different diagnoses is in accordance with established therapeutic guidelines.

PMID- 11301611
TI  - [Intraoperative ultrasonography in laparoscopic cholecystectomy].
AB  - BACKGROUND: Laparoscopic ultrasonography has been increasingly used over the last
      several years as a new imaging modality. This study assessed the effectiveness of
      laparoscopic ultrasonography in detecting main biliary duct stones during
      laparoscopic cholecystectomy. MATERIAL AND METHODS: During the eight-year period
      1991-98, 441 patients treated by laparoscopic cholecystectomy were at the same
      time included in laparoscopic ultrasonography. After port placement and
      dissection of the gallbladder, laparoscopic ultrasonography of the extrahepatic
      common bile duct was performed in the longitudinal plane. RESULTS: Laparoscopic
      ultrasonography failed to recognise the intrapancreatic part of the common bile
      duct in 64 cases (14%). The time used for sonography was approximately eight
      minutes. In this study, common bile duct stones were found in 29 cases (7%). One
      false negative result was recognised. INTERPRETATION: Laparoscopic
      ultrasonography is a safe, repeatable, noninvasive and cost-effective procedure,
      but a considerable learning curve is necessary in order to optimise its efficacy.
      Once learned, however, the method can be used as a primary screening procedure
      for bile duct calculi.

PMID- 11301610
TI  - [Diagnosis of primary Sjogren's syndrome].
AB  - BACKGROUND: The diagnosis of primary Sjogren's syndrome largely depends on
      pathological findings at lower lip biopsy, or the presence of anti SSA and/or
      anti SSB antibodies. The present study evaluated which clinical and laboratory
      features among patients with sicca symptoms could predict a positive biopsy.
      MATERIAL AND METHODS: All 217 patients evaluated for sicca symptoms at Aust-Agder
      Central Hospital, Arendal, Norway from 1989 through 1998 were retrospectively
      reviewed. RESULTS: 136 biopsies were performed. 59 patients were diagnosed with
      primary Sjogren's syndrome. A reduced Schirmer I test combined with either an
      elevated ESR, positive ANA or elevated serum gammaglobulin had a high positive
      predictive value for primary Sjogren's syndrome. INTERPRETATION: Among patients
      with sicca symptoms, those with laboratory evidence of inflammation, autoimmunity
      or exocrine dysfunction should be subjected to a lower lip biopsy for a final
      diagnosis of primary Sjogren's syndrome.

PMID- 11301612
TI  - [Transesophageal echocardiography at a small Norwegian district hospital].
AB  - Transoesophageal echocardiography in a routine setting in a small Norwegian
      district hospital (catchment area population 30,000) during a 12-month period is
      presented. The method is relatively new and is seldom used at district hospitals.
      We therefore find it of interest to report our experience with the method. During
      1998 a total of 868 echocardiographies were performed, 167 of which were
      transoesophageal. Our hospital had at that time three people performing the
      investigation, two of which were cardiologists. The mean age of patients was 69.9
      years; men 68.4, women 71.8 years. 60% of the investigations were on inpatients;
      40% of the transoesophageal investigations were performed as emergencies or
      subacutely. The transoesophageal echoes were performed following the usual
      application criteria: 56 were done to evaluate possible cardial source of
      embolism, 32 valve disease, 24 to verify or follow endocarditis, 14 patients were
      seen prior to electroconversion. In six of these, large thrombi in the left-side
      cardiac chambers were found and electroconversion was not performed. All these
      patients had been on well controlled anticoagulant treatment for three or more
      weeks prior to the investigation. Seven patients were studied due to probable
      aortic pathology. Patients with emphysema, chronic lung disease, radiation
      sequelae or others with no parasternal or subxiphoid access had transoesophageal
      echo performed. Intravenous diazepam was only used in four of 167 investigations.
      This was of great importance for including the method in our outpatient clinic
      routine. The frequent observation of intracardiac thrombi has let us to
      incorporate transoesophageal echocardiography into a routine setting for all
      patients prior to electroconversion and for those with stroke in order to
      optimise treatment.

PMID- 11301613
TI  - [Diagnostic transmission electron microscopy].
AB  - BACKGROUND: Transmission electron microscopy (TEM) is an important diagnostic
      tool in surgical pathology. MATERIAL AND METHODS: We give an overview, based on
      our own experience, of the application of TEM in diagnostic pathology. RESULTS:
      In spite of its potential for high-grade resolution, the actual use of TEM in
      diagnostic pathology is rather limited. TEM is mandatory in the examination of
      kidney and muscle biopsies and is often indicated when a metabolic disease is
      suspected. However, in many centres its importance in tumour pathology has
      declined because of the advances in the field of immunohistochemistry. TEM
      requires a great deal of resources and high levels of skills in tissue processing
      and diagnostic interpretation. INTERPRETATION: The TEM diagnosis must be
      integrated with light microscopical and, often, immunohistopathological findings,
      as well as with the clinical data. We therefore recommend close collaboration
      between the clinician and the laboratory with regard to biopsy indication,
      handling of samples, and the final diagnosis.

PMID- 11301614
TI  - [Cluster headache--clinical aspects, pathophysiology and treatment].
AB  - EPIDEMIOLOGY: Cluster headache afflicts somewhat less than one in thousand in the
      general population. The majority of sufferers are men. CLINICAL FEATURES: The
      syndrome is characterized by frequent attacks of intense pain localized in and
      around the eye on one side, characteristically accompanied by conjunctival
      injection and lacrimation in this eye, along with nasal stuffiness on the same
      side and sometimes a Horner's syndrome. All symptoms and signs are strictly
      unilateral and occur during attacks lasting between 15 minutes and three hours.
      The attacks occur from once to eight times daily during a period lasting from
      some weeks to months. After a remission of varying duration, the same pattern
      recurs. PATHOPHYSIOLOGY: Recent findings suggest a pivotal role of the
      hypothalamus in relation to the pathophysiology. TREATMENT: Sumatriptan injection
      or oxygen inhalation aborts pain attacks in most patients. The most frequently
      used prophylactic agents are verapamil, lithium and steroids.

PMID- 11301615
TI  - [One year's written drug information to a general practitioner].
AB  - BACKGROUND: It is a general impression that by far the greater part of drug
      information to general practitioners is provided by drug manufacturers rather
      than by independent sources. However, the extent of such information has not
      previously been quantified in Norway. MATERIAL AND METHODS: All written drug
      information received by a general practitioner in 1999 was registered. RESULTS: A
      total of 5,669 pages of drug information were received. Of these, 5,115 pages
      (90.2%) came from drug manufacturers. On average, 12 pages with drug
      advertisements and information on six different pharmaceutical products were
      received every day. INTERPRETATION: This study verifies that a very high
      proportion of the drug information to a general practitioner is provided by the
      pharmaceutical industry.

PMID- 11301616
TI  - [Depression--socioeconomic perspectives].
AB  - BACKGROUND: Depression is a major health problem, and there is a growing
      awareness of the economic burden imposed by depressive disorders. MATERIAL AND
      METHODS: A review of the literature on the societal cost of depression is
      presented in a comparison of the two major studies on the topic and a discussion
      of the feasibility of reducing costs. RESULTS: Estimating the societal cost of
      depression is complicated and estimates differ a great deal. The costs are,
      however, considerable with morbidity costs constituting the largest component.
      Depression is underdiagnosed and undertreated, but the majority of patients can
      be effectively treated; thus, in theory, cost reductions should be feasible.
      After the controversial Gotland study it was claimed that improving the skills of
      general practitioners in diagnosing and treating the disorder might reduce its
      societal costs considerably. However, these results were not reproduced in the
      randomized controlled Hampshire study. INTERPRETATION: It is uncertain to what
      degree it is possible to reduce the societal costs of depression. Research on the
      health economics of depressive disorders should be given priority.

PMID- 11301617
TI  - [Vertebral fractures--a big health problem for elderly women?].
AB  - BACKGROUND: The term osteoporosis often conjures up an image of deformed spines,-
      small stooping ladies burdened with back pain. Most modern medication against
      osteoporosis has documented effect first and foremost against vertebral
      fractures. However, are vertebral fractures a public health issue, and are they
      frequent and serious enough to warrant aggressive and expensive preventive
      measures? MATERIAL AND METHODS: Through search in Medline with the terms
      "osteoporosis", "vertebral fracture*" and "vertebral deformities", we identified
      and reviewed a total of 222 scientific articles on vertebral fractures. RESULTS:
      Incident vertebral deformities entail temporary complaints, and the consequences
      of prevalent deformities are minute unless there are several deformities. Less
      than 8% of back pain among the elderly can be attributed to vertebral
      deformities. A large double-blind, randomised clinical trial demonstrates that
      treatment that halves the risk of new vertebral deformities barely affects the
      occurrence of back pain or disability. INTERPRETATION: Even if some patients'
      suffering is attributable to vertebral deformities, we conclude that vertebral
      deformities represent a minor public health problem. As a consequence, studies
      exploring predictors of painful vertebral fractures are warranted; furthermore,
      more documentation on prevention of non-vertebral fractures is needed.

PMID- 11301618
TI  - [Olav Egeberg--hereditary antithrombin deficiency and thrombophilia].
AB  - In 1965 Olav Egeberg (1916-77) presented the first report that linked a defined,
      hereditary defect in the control of blood coagulation to thrombotic disease.
      Having examined a family in which several members had sustained venous
      thrombosis, he demonstrated that antithrombin activity was clearly subnormal in
      the affected members. Heparin cofactor activity was also subnormal in these
      persons. This supported the hypothesis that the two activities might reside in a
      single protein. The condition was inherited as an autosomal dominant trait.
      Egeberg's publication initiated thrombophilia as a rewarding research area, and
      also as an important clinical discipline.

PMID- 11301619
TI  - [Treatment of toenail onychomycosis].

PMID- 11301620
TI  - [Approaching the acutely ill child].
AB  - The proper evaluation of the acutely ill infant and child requires a systematic
      approach, and knowledge of normal and pathological clinical findings according to
      age. In this paper guidelines are suggested on how the child may be evaluated
      clinically and by judicious use of supplementary investigations which are readily
      available.

PMID- 11301621
TI  - [Diagnosis and treatment of congenital hyperinsulinism--to Paris at any price?].
AB  - BACKGROUND: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a
      hyperfunctional disorder of pancreatic insulin-producing cells with hypertrophic
      beta-cells present either focally or diffusely. With an estimated frequency of
      1:50,000 live births, Norway will on average have one case per year. It is
      clearly difficult to maintain expertise in diagnostics and treatment with such a
      low incidence. MATERIAL AND METHODS: We report three Norwegian patients with PHHI
      who were successfully treated at Hopital des Enfants Malades in Paris. RESULTS:
      Two patients were shown to have focal hyperinsulinism treated with partial
      pancreas resection. After follow-up of three and a half and two years
      respectively, these patients have normal glucose tolerance and exocrine
      pancreatic function. One patient with diffuse hyperinsulinism was operated with
      subtotal (90%) pancreatectomy. At 2.5-years follow-up this patient has slight
      glucose intolerance whereas her fasting blood glucose is low normal. The exocrine
      pancreatic function is normal. INTERPRETATION: Patients with PHHI should be
      referred to a centre where the possibility of focal hyperinsulinism can be
      thoroughly explored.

PMID- 11301622
TI  - [Screening for osteoporosis in Norway?].

PMID- 11301623
TI  - [Live the wild screening!].

PMID- 11301624
TI  - [Research on impotence and marketing].

PMID- 11301625
TI  - [Small radiation dosages--uncertain effects on human beings].

PMID- 11301626
TI  - [Radiation and health--radiation protection also with low dosage?].

PMID- 11301627
TI  - [Treatment after stroke].

PMID- 11301628
TI  - [Abortion committees and geographical differences].

PMID- 11301629
TI  - [Gestagen supplementation].

PMID- 11301630
TI  - [Statins and muscular adverse effects].

PMID- 11301631
TI  - [Has the family practitioner ceased to examine patients?].

PMID- 11301632
TI  - [Transcendental meditation and the aging process].

PMID- 11301633
TI  - Laboratory safety--coverage of the LS&EM (Laboratory Safety & Environmental
      Management) '99 conference.

PMID- 11301634
TI  - Optical coherence tomography in dermatology: a review.
AB  - BACKGROUND/AIMS: Optical coherence tomography (OCT) is a non-invasive technique
      for morphological investigation of tissue. Since its development in the late
      1980s it is mainly used as a diagnostic tool in ophthalmology. For examination of
      a highly scattering tissue like the skin, it was necessary to modify the method.
      Early studies on the value of OCT for skin diagnosis gave promising results.
      METHODS: The OCT technique is based on the principle of Michelson interferometry.
      The light sources used for OCT are low coherent superluminescent diodes operating
      at a wavelength of about 1300 nm. OCT provides two-dimensional images with a scan
      length of a few millimeters (mm), a resolution of about 15 microns and a maximum
      detection depth of 1.5 mm. The image acquisition can be performed nearly in real
      time. The measurement is non-invasive and with no side effects. RESULTS: The in
      vivo OCT images of human skin show a strong scattering from tissue with a few
      layers and some optical inhomogeneities. The resolution enables the visualization
      of architectural changes, but not of single cells. In palmoplantar skin, the
      thick stratum comeum is visible as a low-scattering superficial well defined
      layer with spiral sweat gland ducts inside. The epidermis can be distinguished
      from the dermis. Adnexal structures and blood vessels are low-scattering regions
      in the upper dermis. Skin tumors show a homogenous signal distribution. In some
      cases, tumor borders to healthy skin are detectable. Inflammatory skin diseases
      lead to changes of the OCT image, such as thickening of the epidermis and
      reduction of the light attenuation in the dermis. A quantification of treatment
      effects, such as swelling of the horny layer due to application of a moisturizer,
      is possible. Repeated measurements allow a monitoring of the changes over time.
      CONCLUSION: OCT is a promising new bioengineering method for investigation of
      skin morphology. In some cases it may be useful for diagnosis of skin diseases.
      Because of its non-invasive character, the technique allows monitoring of
      inflammatory diseases over time. An objective quantification of the efficacy and
      tolerance of topical treatment is also possible. Due to the high resolution and
      simple application, OCT is an interesting addition to other morphological
      techniques in dermatology.

PMID- 11301635
TI  - Surface free energy characterization of vernix caseosa. Potential role in
      waterproofing the newborn infant.
AB  - BACKGROUND/AIMS: Vernix caseosa is a proteolipid biofilm synthesized by the human
      fetus, which progressively covers the fetal skin surface during the last
      trimester of pregnancy. The exact physiological functions of vernix are unclear.
      Hypothetically, it serves a role in "waterproofing" the fetus during the critical
      period of epidermal barrier development before birth. Vernix may also play a role
      in adaptation of the fetal skin surface to the dry, cool extrauterine environment
      after birth. Given the strategic position of vernix on the fetal skin surface and
      the rapidly changing environment encountered by the skin at birth, we proposed
      that investigation of vernix surface characteristics would facilitate
      understanding its putative physiological roles. METHODS: In this paper, we
      focused on the determination of the surface free energy (SFE) of vernix caseosa.
      Different approaches were used to calculate the SFE of vernix from contact angle
      (theta) measurements between vernix and various liquids (benzyl alcohol,
      diiodomethane, glycerol, and water). The critical surface tension (CST) of vernix
      was calculated using Zisman plots. The dispersive and the polar components of
      vernix SFE were calculated using the Owens-Wendt geometric mean method. Vernix
      was contrasted with petrolatum, a commonly used skin protectant. RESULTS: CST of
      fresh vernix was 40.5 dyne/cm while that of petrolatum was 35.8 dyne/cm. Fresh
      vernix polar SFE was 1.5 dyne/cm while petrolatum had almost no polar SFE
      component (0.03 dyne/cm). For all liquids (except the nonpolar diiodomethane)
      there was a significant decrease in contact angle with time. CONCLUSIONS: The CST
      and the total SFE values suggest that vernix has very low surface energy and is
      highly unwettable. These findings are significant insofar as the main component
      in vernix is water, which is highly energetic. Although vernix has a very high
      water content, the major part of its SFE is hydrophobic (dispersive). The limited
      interaction between vernix and hydrophilic liquids supports the hypothesis that
      vernix acts as a natural protectant cream to "waterproof" the fetus in utero
      while submerged in the amniotic fluid.

PMID- 11301636
TI  - Viscoelastic properties of human skin and processed dermis.
AB  - BACKGROUND/AIMS: The purpose of this work is to attempt to determine the elastic
      spring constant for collagen and elastic fibers (elastin) in skin and to
      determine if the values of these elastic constants are similar to those reported
      for other tissues. METHODS: We studied the viscoelastic mechanical properties of
      human skin and dermis by measuring the incremental stress-strain behavior.
      Elastic stress-strain curves were used to obtain the elastic spring constant of
      elastin and collagen while the collagen fibril length was obtained from the slope
      of viscous stress-strain curves. RESULTS: Our results suggest that the elastic
      spring constant for elastin is about 4.0 MPa while that for collagen is about 4.4
      GPa. The former value is similar to that calculated for ligamentum nuchae while
      the latter value is about 70% of the value found for tendon and self-assembled
      type I collagen fibers. The differences between the elastic constants for
      collagen molecules in tendon and skin is hypothesized to reflect the higher
      molecular tilt angle and lower D period found in skin compared to tendon as well
      as a shorter fibril length. CONCLUSION: The differences in the collagen types
      present in skin and tendon may influence collagen self-assembly and the resulting
      viscoelastic properties.

PMID- 11301637
TI  - The Visi-Chroma VC-100: a new imaging colorimeter for dermatocosmetic research.
AB  - BACKGROUND/AIMS: It was the aim of this study to carry out a comparative
      evaluation in vitro on standardized color charts and in vivo on healthy subjects
      using the Visi-Chroma VC-100, a new imaging tristimulus colorimeter and the
      Minolta Chromameter CR-200 as a reference instrument. The Visi-Chroma combines
      tristimulus color analysis with full color visualization of the skin area
      measured. The technical performances of both instruments were compared with the
      purpose of validating the use of this new imaging colorimeter in dermatocosmetic
      research. METHODS: In vitro L*a*b* color parameters were taken with both
      instruments on standardized color charts (Macbeth and RAL charts) in order to
      evaluate accuracy, sensitivity range and repeatability. These measurements were
      completed by in vivo studies on different sites of human skin and studies of
      color changes induced by topical chemical agents on forearm skin. The accuracy,
      sensitivity range and repeatability of measurements of selected distances and
      surfaces in the measuring zone considered and specific color determinations of
      specific skin zones were also determined. RESULTS: The technical performance of
      this imaging colorimeter was rather good, with low coefficients of variation for
      repeatability of in vitro and vivo color measurements. High positive correlations
      were established in vitro and in vivo over a wide range of color measurements.
      The imaging colorimeter was able to measure the L*a*b* color parameters of
      specific chosen parts of the skin area considered and to measure accurately
      selected distances and surfaces in the same skin site considered. CONCLUSION:
      These comparative measurements show that both instruments have very similar
      technical performances and that high levels of correlation were obtained in vitro
      and in vivo using the L*a*b* color parameters. In addition, the Visi-Chroma
      presents the following improvements: 1) direct visualization and recording of the
      skin area considered with concomitant color measurements; 2) determination of the
      specific color parameters of skin areas chosen in the total measuring area; and
      3) accurate determination of selected distances and surfaces in the same skin
      areas chosen.

PMID- 11301638
TI  - The efficiency of humectants as skin moisturizers in the presence of oil.
AB  - BACKGROUND/AIMS: The research on the treatment of "dry skin syndrome" is hampered
      by the lack of a suitable animal model. Formerly, we developed a validated guinea
      pig in vivo model in which the dry skin syndrome persists at least for 1 week. We
      can, therefore, compare the pharmacological effectiveness of known and potential
      moisturizers for the treatment of dry skin syndrome. Our aim is to study whether
      the moisturizing efficiency of humectants depends on the solvents in which they
      are dissolved. METHODS: "Dry skin syndrome" was induced on the shaved skin on one
      side of guinea pigs by daily application of 2% sodium lauryl sulphate in
      deionized water (SLS) for 3 days. The other shaved side was used as control.
      After ascertaining skin dryness, that side was treated for 6 days with glycerol
      or 1,2-hexanediol in different solvents: water, or medium chain triglycerides
      (MCT) or mixtures of MCT with isopropyl alcohol in different proportions.
      Measurement of the in vivo moisturizing effect was carried out by a Comeometer CM
      825; erythema was measured by a Mexameter MX 16. RESULTS: Treatments with
      glycerol (1M) in water reversed the skin dryness shown by both instruments. When
      dissolving glycerol in MCT, no moisturizing effect was found, probably because
      glycerol does not dissolve in the oil. No moisturizing effect was found with
      different combinations of glycerol in the mixtures of MCT and isopropyl alcohol.
      No moisturizing effect was found using another polyol moisturizer: 1,2 hexanediol
      (1M) dissolved in MCT oil. Glycerol or 1,2-hexanediol abolished the erythema only
      when they were dissolved in water alone. CONCLUSION: Polyol moisturizers such as
      glycerol or 1,2-hexanediol do not act in the presence of oils against the sodium
      lauryl sulphate-induced dry skin in our guinea pig model. Since in an oil-in
      water (O/W) emulsion, the water evaporates within several minutes, one has to
      question the ability of moisturizing emulsions to treat dry skin. In such
      instances, one cannot draw conclusions about the moisturizing efficiency of the
      preparation merely from the presence of the humectant. One has to study the
      effect of the finished preparation.

PMID- 11301639
TI  - Sea water or its components alter experimental irritant dermatitis in man.
AB  - BACKGROUND/AIMS: Ocean bathing has been considered "healthy" for skin, but its
      efficacy remains testimonial in nature. Our aim was to evaluate the effects of
      sea water and its main components on experimental irritant contact dermatitis
      induced by sodium lauryl sulphate (SLS) cumulative irritation. METHODS: After
      open application of 2% SLS for 10 min on volar forearm sites, solutions of sea
      water, 500 mM NaCl, 10 mM KCl, 55 mM MgCl2, 10 mM CaCl2, or deionized water were
      separately applied using filter paper discs for 20 min. The procedures were
      repeated daily for 2 weeks. The effects of the treatment were assessed daily
      using measurements of transepidermal water loss (TEWL), as an indicator of
      epidermal barrier function, and capacitance, as a parameter of stratum corneum
      water content. RESULTS: Sea water, NaCl, and KCl significantly inhibited the
      increase of TEWL as compared with deionized water (P < 0.003, P < 0.05, P < 0.05,
      respectively). Sea water and NaCl inhibited the decrease of capacitance as well
      (P < 0.03, P < 0.01). CONCLUSION: The effect of sea water may be attributed to
      skin barrier preservation by NaCl and KCl, and an emollient effect by NaCl.

PMID- 11301640
TI  - Physical and physiological effects of stratum corneum tape stripping.
AB  - BACKGROUND/AIMS: Tape stripping of human stratum corneum has been performed to
      measure stratum corneum mass, barrier function, drug reservoir and percutaneous
      penetration. However, the technique itself requires further development to
      facilitate interpretation. METHODS: In this study we quantified stratum comeum
      (SC) tape stripping and water kinetic parameters utilizing three types of
      adhesive tapes, in an in vivo randomized clinical trial. Stratum corneum was tape
      stripped, and the mass of SC removed by each tape was quantified utilizing a
      protein assay. Transepidermal water loss (TEWL) was measured and barrier
      disruption and SC water kinetics calculated. Three commonly utilized acrylate
      adhesive tapes were utilized and a comparison made between them. RESULTS: Each
      type of tape successfully stripped the stratum corneum, but the rayon tape did
      not induce SC barrier disruption. Neither the type of tape nor the site stripped
      significantly influenced the mass of SC removed. Water kinetic parameters did not
      differ significantly for the tapes that did induce barrier disruption. Individual
      variation in barrier disruption to water following tape stripping was
      demonstrated. CONCLUSION: The tapes utilized removed a similar amount of SC. The
      tapes have a different propensity to cause barrier disruption. Some individuals
      do not demonstrate increased TEWL despite an equivalent mass of SC being removed
      compared to those who do show a response.

PMID- 11301641
TI  - Surfactant irritation: in vitro corneosurfametry and in vivo bioengineering.
AB  - BACKGROUND/AIMS: Irritant reactions to surfactants, cleansing products, soaps and
      detergents are common in clinical and occupational dermatology. Mildness has
      become a major benefit claimed, and testing for mildness now ranks among the
      first concerns of the manufacturing industry. A wealth of publications deals with
      this problem, trying to improve the methodology, reduce the costs of testing and
      facilitate decision-making. Differences in vivo can be measured clinically and/or
      instrumentally. This is difficult, as commercially available products are
      generally safe to use and none are harsh in the absolute sense. METHODS: Nineteen
      different products (syndets, shampoos, personal cleansers), all claiming to be
      mild, were tested in vitro by a newly introduced method, corneosurfametry. For
      evaluating the aggressiveness of the products, the calculation of an index of
      irritation (IOI) was proposed. A concentration-effect curve of sodium lauryl
      sulfate (SLS) as standard and model surfactant was obtained. Some of the products
      were further tested in vivo with a flex wash test and with a soap chamber test
      and compared to SLS. Bioengineering methods (transepidermal water loss TEWL, skin
      color) were used to evaluate the results. RESULTS AND CONCLUSIONS: The results of
      the corneosurfametry allowed us to classify the products in three categories,
      with increasing aggressiveness towards the stratum corneum, according to their
      IOIs. The in vivo tests were not able to discriminate between the products, but
      ranks from the results of the bioengineering measurements showed a good
      correlation between TEWL changes, but not between colour changes, and IOIs from
      corneosurfametry. Corneosurfametry emerged as a simple, low-cost and fast method
      for ranking commercial products according to their mildness. However, the skin
      bioengineering techniques showed that some products could lead to skin reactions,
      such as erythema, that could not be detected by the in vitro technique.

PMID- 11301642
TI  - Reproducibility of repeated measurements on healthy skin with Minolta Chromameter
      CR-300.
AB  - BACKGROUND/AIMS: In this report the reproducibility of measurements with the
      Minolta Chromameter CR-300 on healthy skin was investigated. METHODS: Intra- and
      inter-rater reproducibility, reproducibility with two instruments and repeated
      measurements with a 1 week time lapse were examined on healthy skin of 30
      volunteers by means of intra-class correlation coefficients (ICC) and standard
      error of measurements (SEM). RESULTS: Results showed excellent values for ICC in
      all the four conditions. CONCLUSIONS: On the basis of these results we concluded
      that the instrument provides reliable information and can be used in comparative
      clinical trials.

PMID- 11301643
TI  - Calculation of nail plate and nail matrix parameters by 20 MHz ultrasound in
      healthy volunteers and patients with skin disease.
AB  - BACKGROUND/AIMS: The objective, but noninvasive, assessment of the nail plate and
      nail matrix is of interest in dermatology, and cosmetics as well. These cutaneous
      structures were investigated with 20 MHz ultrasound. This study was performed to
      obtain data on normal nails in adults of different age groups, with a left-right
      comparison, and to investigate nail changes in selected dermatologic diseases.
      METHODS: Healthy controls (n = 34) and patients with dermatologic complaints and
      nail disease (n = 37) were included after informed consent. In the control group,
      18 woman and 16 men with a mean age of 37.2 years (range 15 to 82 years) were
      investigated for age- and gender-related differences. Patients with one of the
      following disorders were investigated: systemic lupus erythematosus (SLE; n =
      11), systemic sclerosis (PSS; n = 8), psoriasis (n = 9), chronic hand eczema (n =
      5), and others (n = 4). Measurements of length and width of the nail plate and
      the lunulae were performed with a micrometer device. Sonography was performed
      with a 20 MHz probe in B-scan mode. RESULTS: The mean nail thickness of healthy
      controls varied between 0.481 mm (right thumb) and 0.397 mm (left fifth finger).
      The nail volume and the matrix volume disclosed a positive, but mostly
      nonsignificant, correlation for all controls. Age-specific differences were
      investigated for both genders. In men and women, the matrix volume increased
      significantly with age. The nail and matrix volume was higher in men than in
      women, independent of age. The left-right comparison disclosed a trend to higher
      nail and matrix volumes on the right hand. In patients with SLE there was an
      increase in nail thickness and in matrix volume. Patients with PSS showed a
      significant decrease in nail thickness and matrix volume. In other diseases the
      measurements disclosed no confident differences to healthy controls. CONCLUSION:
      The 20 MHz ultrasound offers a noninvasive method to calculate nail thickness,
      nail volume and matrix volume in healthy volunteers and in nail disease. Skin
      diseases show characteristic quantitative changes in these parameters.

PMID- 11301645
TI  - Pursuing survey system solutions.

PMID- 11301644
TI  - High-frequency ultrasound imaging of the skin during normal and hypertensive
      pregnancies.
AB  - BACKGROUND/AIMS: Diagnosis of preeclampsia is currently made from blood pressure
      measurements taken at antenatal visits (either at the hospital or in the
      community). The aim of this work was to see whether the presence of underlying
      hypertensive diseases is accompanied by changes in the skin of pregnant women,
      which can be visualized using high-frequency diagnostic ultrasound. METHODS: This
      was a prospective study of pregnant and non-pregnant, hypertensive and non
      hypertensive patients visiting the outpatient department of a central London
      Teaching Hospital. The study group consisted of 93 women, of which 30 were non
      hypertensive in the second trimester of pregnancy, 26 were non-hypertensive in
      the third trimester of pregnancy, 9 were hypertensive in the second trimester of
      pregnancy, and 14 were hypertensive in the third trimester of pregnancy. Fourteen
      non-pregnant women of comparable age were recruited as controls. Changes in
      abdominal skin thickness and also skin structure, as analysed by fractal image
      analysis, was assessed in each patient. RESULTS: In a normal pregnancy, abdominal
      skin gets thinner as pregnancy progresses. In hypertensive patients, the skin
      thickness did not appear to alter. Image analysis of abdominal skin scans showed
      that the skin of non-hypertensive pregnant women and non-pregnant women are
      different. Whereas the analysis of hypertensive pregnant women and non-pregnant
      women showed they were the same. CONCLUSIONS: The data used to compare the groups
      indicates that if the abdominal skin of the patient does not get thinner as the
      pregnancy progresses there is an indication that the patient may be hypertensive.
      The fractal data comparing the groups indicates the following when comparing a
      patient's fractal signature with the non-pregnant control data: If the abdominal
      fractal for a pregnant woman is similar to the control group, there is an
      indication that the patient is hypertensive. It is difficult to predict
      hypertension in patients, and it is possible that a patient could develop severe
      preeclampsia between visits to the antenatal clinics. Therefore, if the high
      frequency ultrasound scanner can pick up potential hypertensives early in
      pregnancy, these women could be identified as potentially high risk.

PMID- 11301646
TI  - Referral arrangements and the law.

PMID- 11301647
TI  - A new look for a changing market.

PMID- 11301649
TI  - [Study on tissue engineering of muscular skeletal system].

PMID- 11301648
TI  - Caregiving. An empathetic approach to dementia.

PMID- 11301650
TI  - [Biomaterial and cells scaffold for tissue engineering uses].

PMID- 11301651
TI  - [Biomemetic surface modification of biomaterials related to tissue engineering].

PMID- 11301652
TI  - [Experiment study of auto-cartilage engineering].
AB  - OBJECTIVE: To engineer diversified shapes of neocartilage from auto-cartilage and
      provide a new method to reconstruct cartilage. METHODS: Cartilage obtained from
      the ear of 5-week-old New Zealand rabbits was cut into pieces of 0.5 mm x 0.5 mm,
      which were seeded onto the three-dimensional polylactic acid foams. The cartilage
      polymer construct was implanted into a subcutaneous pocket of the donor rabbit.
      Animals were sacrificed at 3rd, 6th month after implantation. The retrieved
      implants in each animal were used for gross measurement and histological
      analysis. RESULTS: Gross examinations of the specimens at 6 months after
      implantation revealed that there was neocartilage formation; the maxim size was 8
      mm x 8 mm. The cartilage showed no signs of resorption. Histological evaluation
      confirmed the generation of cartilage. The polymer substrate support cell
      proliferation. The extracellular matrix stained strongly positive for S-GAGs with
      Alcian blue staining. CONCLUSION: Neocartilage can be created using free auto
      cartilage transplantation on appropriate polymer templates.

PMID- 11301653
TI  - [The modification of combined subperiosteal facelift].
AB  - OBJECTIVE: To reposit all the elements of the aging midface more adequately.
      METHODS: We have performed combined facelift on 100 patients using extended
      subperiosteal dissection or sub-SMAS and subcutaneous dissection. In particular,
      the zygomatic arch subperiosteal dissect releases the attachment of the zygomatic
      ligament. RESULTS: In this group of 100 patients, postoperative follow-up showed
      that this technique can restore the initiate anatomical relationship of multiple
      tissue layers of the face, provides the patient with both an excellent nasolabial
      fold and jawline contour without damage of the frontal branch of the facial
      nerve. CONCLUSION: This technique is most suitable for the patients about 40
      years old.

PMID- 11301654
TI  - [Evaluation of derma and fat combined pedicled superficial temporal fascia flap
      for reconstruction of facial depression].
AB  - OBJECTIVE: To evaluate the curative effect of derma and fat combined pedicled
      superficial temporal fascia flap for reconstruction of facial depression. METHOD:
      Postoperative follow-up and comparative study were performed. 10 cases of facial
      depression deformities were involved, in which 5 cases were hemifacial atrophy,
      and 5 cases were branchial arch maldevelopment. RESULTS: Postoperative follow-up
      for 1-3 years showed that the method produced better results in branchial arch
      depression than in hemifacial atrophy. The combined tissue used in plomb of
      branchial arch maldevelopment had a low ratio of anaphase absorption, maintaining
      a satisfactory long-term full contour. In plomb of hemifacial atrophy, the
      anaphase absorption ratio of the was combined tissue approximately 20%-40%.
      CONCLUSIONS: The noxa of depression ought to be noticed when this method is used
      in reconstruction of facial depression. The exorbitant plomb is inadvisable for
      facial depression of branchial arch maldevelopment. However, in facial depression
      of hemifacial atrophy, in considering anaphases absorption, the suitable
      exorbitant plomb is reasonable for better future results.

PMID- 11301655
TI  - [Clinical analysis of 40 patients who were re-operated after prosthetic
      augmentation mammaplasty].
AB  - OBJECTIVE: To summarize the reasons of complications after prosthetic
      augmentation mammaplasty and explore the optimal preventive measures and therapy.
      METHOD: The reasons for 40 patients who were re-operated on after prosthetic
      augmentation mammaplasty were analyzed in as many aspects as possible, such as
      the location of the incision, the type of the prosthesis, etc. Preventive
      measures and therapy of the complications were also summarized. RESULTS: Capsular
      contracture was the most common reason for reoperation. The second was prosthetic
      rupture and translocation. The main reasons resulting in complications included
      impertinent indications, poor quality of the prosthesis and an incompetent
      surgeon. CONCLUSIONS: The key to reduce the complications is proper selection of
      good prosthesis, strict indications, better comprehension of the knowledge about
      prosthetic augmentation mammaplasty and a qualified plastic and aesthetic surgeon
      for the operation. The inareolar incision is the best choice to remedy the
      complications.

PMID- 11301656
TI  - [Abdominoplasty with a combined technique of lipectomy and liposuction].
AB  - OBJECTIVE: To evaluate an abdominoplasty technique combined with lipectomy and
      liposuction. METHODS: Twenty-five patients were undergoing for the abdominoplasty
      with lipectomy and liposuction in the same operation procedure. A public incision
      with W-shape was used for the lower abdominal lipectomy, and the upper abdomen
      was treated with an electronic liposuction technique. After the operation, each
      patient was followed up for evaluation of the results. RESULT: All of the
      patients got good contour of the abdomen without obvious complications. The
      abdominal perimeter was shrunk form 5 cm to 15 cm with over 3 months follow-ups.
      CONCLUSIONS: The combination of lipectomy and liposuction may be a good and safe
      method for abdominoplasty. The abdominal flap during the lipectomy could achieve
      higher survival rate than the traditional technique, due to the less injury on
      the neurovascular structures sustained by the liposuction procedure.

PMID- 11301657
TI  - [Comparison of occlusive dressing and vaseline gauze on the skin graft donor site
      wound healing].
AB  - OBJECTIVE: To observe the effect of occlusive environment on wound healing of the
      skin graft donor site. METHODS: The wound healing of the skin graft donor site in
      adults was studied by clinic observation, histological, histochemical and
      electromicroscopical examinations. RESULTS: The wound under an occlusive moisture
      environment healed faster and the inflammation was more serious at the early
      stage of wound healing while the macrophages appeared more and earlier.
      CONCLUSIONS: The wound of a skin graft donor site in an occlusive moist condition
      would heal faster than that covered with conventional Vaseline gauze. The more
      serious inflammation and the more macrophages may be related to the result.

PMID- 11301658
TI  - [Microwave heating modulation of skin fibrosis in chronic extremity lymphedema].
AB  - OBJECTIVE: To observe the effects of microwave heating on skin fibrosis in
      chronic extremity lymphedema. METHODS: Skin specimens from 8 cases of chronic
      limb lymphedema were tested by in situ hybridization (ISH) combined with avidin
      biotin peroxidase (ABC) immunohistochemistry for detection of TGF-beta,
      procollagen I, procollagen III mRNAs and corresponding peptides expressions.
      RESULTS: It was discovered that expressions of TGF-beta 1 peptide were located at
      the spinous and granular layer of the epidermal cells with a great amount of
      dermal collagen I, III formation in accordance with high expressions of TGF-beta,
      procollagen I, procollagen III mRNAs in the dermal and subcutaneous tissue
      fibroblasts. After microwave heating treatment, the epidermal expression of TGF
      beta 1 and relative TGF-beta, procollagen I, procollagen III mRNAs expressions in
      dermal fibroblasts were greatly reduced. The smaller calibre of collagen fibers
      after microwave heating was also observed. CONCLUSIONS: It is indicated that
      fibrosis in lymphedema is resulted from overexpressions of relevant genes like
      TGF-beta and subsequent extracellular matrixes (ECM) syntheses and deposition.
      Microwave heating can reduce fibroblast expressions of TGF-beta, procollagen I,
      procollagen III mRNAs as well as TGF-beta peptide synthesis, inhibiting ECM
      syntheses and deposition and finally reverse the skin fibrosis process.

PMID- 11301659
TI  - [Suture distraction osteogenesis for closure of cleft palate in the dog: long
      term effect and its influence on facial growth].
AB  - OBJECTIVE: The purpose of the study was to evaluate the long-term effect and its
      influence on facial growth of suture distraction osteogenesis for closure of
      cleft palate. METHOD: 14 Beagle dogs were used in the study. Six of them were in
      the experimental group, eight served as the control. Direct measurements were
      taken on dry skulls of the dogs and the data were analysed statistically.
      RESULTS: The results showed that bony healing at the midline between the two
      horizontal portions of the palatine bones appeared in all the experimental dogs.
      There were no significant differences in the variables of facial length and
      height between the two groups. But the facial width and the distance between the
      two vertical portions of the palatine bones were significantly less in the
      experimental dogs than the control. CONCLUSIONS: It is suggested that bony repair
      of the cleft could be accomplished permanently with the technique of sutural
      distraction. This technique had no influence on facial length and height growth,
      but could led to underdevelopment of the width of the face and the respiratory
      tract of the palatal portion.

PMID- 11301660
TI  - [A long-term study of a small-caliber arterial autograft used for repair of a
      large-caliber arterial defect].
AB  - OBJECTIVE: The long-term fate of a small arterial graft used to repair a large
      diameter artery was studied in this study. METHODS: An end segment of the tail
      artery (0.3-0.4 mm in diameter) was transplanted to the defect of the carotid
      artery (1.0-1.4 mm in diameter) in 50 rats. The vessel grafts were examined
      histologically at 3 weeks and 5, 10 and 12 months after implantation. RESULTS: At
      3 weeks, intimal thickening of the grafts was mild and present only in regions
      adjacent to the anastomosis. At 5 months, severe intimal thickening was seen
      along the entire graft wall. At 10 and 12 months, the intimal thickening reduced.
      Regression of the thickening was uneven within the graft wall. The adventitia
      thickened at the early postoperative period and reduced at the end of this study.
      The patency rate of the grafts at 12 months postoperation was 95% (19/20).
      Angiography indicated that the grafts stopped expanding after 5 months and were
      only slightly smaller than the recipient arteries at 12 months postoperation.
      CONCLUSION: These results suggest that a small, autogenous arterial graft may
      effectively repair a large-calibre arterial defect.

PMID- 11301661
TI  - The role of volunteers in hospice bereavement support in New Zealand.
AB  - The purpose of this study was to assess the role of hospice bereavement
      volunteers in New Zealand. Participants included 34 co-ordinators and 121
      volunteers from 26 hospices. Co-ordinators and volunteers were asked about the
      perceived adequacy of their training, support and deployment. Findings revealed
      that most volunteers were recruited through personal contact and newspapers. They
      reported being strongly motivated to help others (88%) and most had previous
      bereavements (71%). Volunteers provided a wide range of bereavement support
      within the home and/or hospice. They listed twice as many 'satisfying' compared
      to 'least satisfying' (442 vs 207) aspects of their work, although 50% reported
      their work to be emotionally distressing and 28% had problems with 'boundaries'.
      Two-thirds had generic volunteer training, but only a third had specific training
      in bereavement. Volunteers appeared to be largely unaware of the need for
      specialist training, or supervision, which raises issues about the quality of
      services provided.

PMID- 11301662
TI  - The meaning of the lived experience of hope in patients with cancer in palliative
      home care.
AB  - The aim of this study was to illuminate the meaning of the lived experience of
      hope in patients with cancer in palliative home care. Narrative interviews with
      11 patients were interpreted using a phenomenological-hermeneutic method,
      inspired by Ricoeur. The findings revealed a tension between hoping for
      something, that is a hope of getting cured, and living in hope, that is
      reconciliation and comfort with life and death. This tension is highlighted,
      according to the views of the French philosopher Gabriel Marcel, as a state of
      'recollection'. The interviewees told of the hope of living as normally as
      possible and of the experience of confirmative relationships as dimensions of
      their lived experience of hope. These findings show that hope is a dynamic
      experience, important to both a meaningful life and a dignified death, for those
      patients suffering from incurable cancer.

PMID- 11301663
TI  - Spiritual thoughts, coping and 'sense of coherence' in brain tumour patients and
      their spouses.
AB  - When a person is diagnosed with a life-threatening disease, existential questions
      are easily triggered. The aims of this study were to explore to what extent brain
      tumour patients and their next of kin were able to cope, understand and create
      meaning in their situation, to explore whether spirituality could be supportive
      and to analyse whether these concepts are related to Antonovsky's concept of
      sense of coherence. Using a purposive sampling technique, 20 patients and 16 of
      their next of kin took part in tape-recorded interviews. A content and context
      analysis was performed using a hermeneutic approach. We found that
      comprehensibility was to a large extent constructed by the patient's own thoughts
      and theories, despite an insecure situation. Manageability was achieved by active
      information-seeking strategies, by social support and by coping, including
      positive reinterpretation of the situation. Meaningfulness was central for
      quality of life and was created by close relations and faith, as well as by work.
      A crucial factor was whether the person had a 'fighting spirit' that motivated
      him or her to go on. As only three patients were believers, trust in God had
      generally been replaced by a belief and confidence in oneself, in science, in
      positive thinking and by closeness to nature. Sense of coherence as a concept can
      explain how exposed persons handle their situation. In its construction, sence of
      coherence integrates essential parts of the stress/coping model
      (comprehensibility, manageability) and of spirituality (meaning).

PMID- 11301664
TI  - Implementation of the World Health Organization 'analgesic ladder' in Saudi
      Arabia.
AB  - The European School of Oncology recently sponsored a symposium at the King Faisal
      Specialist Hospital in Saudi Arabia entitled 'The modern management of advanced
      cancer: how to help your patients'. During this symposium, a workshop was
      organized in order to address the problem of 'the availability and the
      distribution of narcotics' for patients with advanced symptomatic cancer in the
      Kingdom of Saudi Arabia. Many country-wide problems were identified including the
      lack of specific information, religious acceptance and education for patients,
      health care professionals and government, the availability of medications and
      access to palliative care. It was suggested that clear protocols for the
      acceptance of patients into palliative care programmes, the prescribing and
      delivery of medication, and their availability throughout the country, be
      established. The goal of allowing patients with advanced cancer to die with
      dignity and without pain was identified as a worthy one and one that would be
      appreciated not only by patients themselves but by their relatives, carers,
      religious leaders and government. The workshop discussed some of the ways of
      trying to achieve this goal, and its conclusions are reported here.

PMID- 11301665
TI  - Use of bisphosphonates for the treatment of metastatic bone pain. A survey of
      palliative physicians in the UK.
AB  - A postal survey of palliative physicians in the UK conducted in 1999 demonstrated
      widespread use of bisphosphonates for treatment of bone metastases from a variety
      of tumour types. In the absence of clear guidelines, however, there was found to
      be wide variation in treatment regimes, and opinions about efficacy varied
      greatly between respondents. Pamidronate was the most popular choice of drug, but
      a number of respondents chose to use clodronate, often on the basis of cost
      saving. A high level of uncertainty about how to monitor side-effects and
      efficacy was revealed. As well as acute treatment of severe pain, a significant
      number of respondents reported treating patients prophylactically, and the
      majority thought that their use of bisphosphonates would increase over the next 2
      years. The potential financial consequences of this are considered.

PMID- 11301666
TI  - Drugs and syringe drivers: a survey of adult specialist palliative care practice
      in the United Kingdom and Eire.
AB  - Subcutaneous delivery of drugs using a syringe driver is common practice within
      specialist palliative care units. There is, however, little documented
      information regarding clinical practice. A survey performed in 1992 reported that
      at least 28 drugs were used in combination with others in a single syringe
      driver. The aim of the present study was to reassess practice in this field and
      to enquire more specifically about newer drugs. Postal questionnaires were sent
      to all adult specialist palliative care in-patient units in the UK and Eire (n =
      208). One hundred and sixty-five units (79%) responded. The most common syringe
      driver in use was the Graseby 26 (61% of responding units). Most units delivered
      the contents of the syringe over 24 h, and water was usually used as the diluent
      in 90% of cases. The maximum number of drugs that respondents were prepared to
      mix in a single syringe was usually three (51%) or four (35%). In the UK, all
      units used diamorphine in doses from 2.5 mg/24 h upwards. All respondents also
      used haloperidol, in doses from 0.5 to 60 mg/24 h. A total of 28 different drugs
      were used in syringe drivers. The most common combinations were diamorphine and
      midazolam (37%), diamorphine and levomepromazine (35%), diamorphine and
      haloperidol (33%), and diamorphine and cyclizine (31%). In conclusion, there is
      much in common with regard to the way in which drugs are delivered in syringe
      drivers. However, a wide variety of drugs and drug combinations are still in use.

PMID- 11301667
TI  - Are continuing care beds in private nursing homes the answer to providing care
      for the longer-term dying?

PMID- 11301668
TI  - Interviewing terminally ill people: is it fair to take their time?

PMID- 11301669
TI  - A personal initiative to improve palliative care in India: 10 years on.

PMID- 11301670
TI  - Clinical research in palliative care: patient populations, symptoms,
      interventions and endpoints.
AB  - Clinical trials in palliative care involve multiple issues relating to patient
      populations, interventions and endpoints. Careful data collection and analysis of
      variables are vital for good clinical research in this complex area.

PMID- 11301671
TI  - Paternalism within judgements of futility.

PMID- 11301672
TI  - Paracentesis in a home care setting.

PMID- 11301673
TI  - Research and ethical scrutiny: an editor's dilemma?

PMID- 11301674
TI  - The first year of grief and bereavement in close family members to individuals
      who have died of cancer.
AB  - Using a systematic and standardized method this longitudinal study examines
      changes in grief reactions in a sample of close family members (n = 183) to
      individuals who had died of cancer. The respondents were followed for 1 year
      after the loss. The study sample originated from a cluster randomized trial
      evaluating comprehensive palliative care (intervention) against conventional care
      (control). Hence, we also compared grief reactions among close family members to
      the patients in the intervention and control groups. Overall, the family members'
      grief reactions, as measured by the second part of the Texas Revised Inventory of
      Grief (TRIG), showed a significant decline over the period studied. However, we
      found no significant differences in grief reactions between the family members to
      the intervention and control patients at any point in time, and the pattern of
      change did not differ significantly for the two groups.

PMID- 11301675
TI  - Overdiagnosis and overtreatment.

PMID- 11301676
TI  - Weighing in on certification.

PMID- 11301677
TI  - Lashing out.

PMID- 11301678
TI  - Coronary bypass and dysphagia.

PMID- 11301679
TI  - 'Clean' vs. 'sterile'.

PMID- 11301680
TI  - Breast cancer: risk, prevention, & tamoxifen.

PMID- 11301681
TI  - Another view of tamoxifen.

PMID- 11301682
TI  - Emergency: necrotizing fasciitis.

PMID- 11301683
TI  - Fabry disease.

PMID- 11301684
TI  - Three herbs you should get to know.

PMID- 11301685
TI  - Selective COX-2 inhibitors.

PMID- 11301686
TI  - A decision that defies logic.

PMID- 11301687
TI  - Therapeutic cannabis.

PMID- 11301688
TI  - An apple a day.

PMID- 11301689
TI  - Workplace violence.

PMID- 11301690
TI  - Dot-calm.

PMID- 11301691
TI  - When health care harms.

PMID- 11301692
TI  - [Communicable disease control and politics in the Baltic States].

PMID- 11301693
TI  - [Congenital metabolic diseases--curiosity cabinet or clinical everyday?].

PMID- 11301694
TI  - [Helicobacter pylori--how much a friend and how much an enemy?].

PMID- 11301695
TI  - [Myocardial infarction treated with angioplasty].

PMID- 11301696
TI  - [Hundred patients with acute myocardial infarction treated with primary
      angioplasty].
AB  - BACKGROUND: Much attention has lately been focused on primary angioplasty in the
      treatment of acute myocardial infarction. This report describe our results in 100
      patients. MATERIAL AND METHODS: 100 consecutive patients with acute ST elevation
      myocardial infarction and a history of less than six hours were treated with
      primary angioplasty. The mean time from start of symptoms until establishment of
      reperfusion of the infarct related artery was 224 minutes; "the door-to-balloon"
      time was 69 minutes. RESULTS: Angioplasty was successful in 95% of all patients.
      Mean ejection fraction measured before discharge in 71 patients was 56%. Hospital
      and 30-days' mortality was 1%. New revascularization was needed in 6%. Average
      observation period in the coronary care unit was 1.8 days; no patient needed
      treatment for ventricular arrhythmias after angioplasty. The first 24 hours 24%
      had symptomatic congestive heart failure, reduced to 11% at hospital discharge on
      day 6. Acute rehospitalization within the first 30 days was necessary in 7%, but
      only in 2% for chest pain. INTERPRETATION: Our results are comparable to those of
      other high volume centres and show well preserved ventricular function and low
      hospital and 30-days' morbidity and mortality.

PMID- 11301697
TI  - [Angiographic results of primary angioplasty in acute myocardial infarction].
AB  - BACKGROUND: Percutaneous angioplasty is an alternative to thrombolysis to
      reestablish coronary blood flow in patients with transmural myocardial
      infarction. At present, this treatment option is not widely accepted in Norway.
      MATERIAL AND METHODS: From 1996 to 1998, one hundred consecutive patients were
      treated with angioplasty for acute transmural infarction. The angiography showed
      one-vessel disease in 55%, two-vessel in 25%, and multivessel in 20%. The infarct
      related artery was the LAD in 44%, the CX in 14%, the RCA in 41%, and bypass
      graft in one. 92% had TIMI 0 or 1 flow. Stent was placed in 73%, GPIIb/IIIa was
      used in 11% and temporary pacemaker placed in 5%. RESULTS: Successful angioplasty
      was performed in 95%, 3% was not done, and 2% failed. Peripheral stenoses were
      treated in 15% and stenoses in other arteries in 10%. Complications and events
      within 24 hours related to the angioplasty were seen in 9%. CONCLUSION: Primary
      angioplasty for acute myocardial infarction can be done with high primary
      success, good short-term results and few complications.

PMID- 11301698
TI  - [Serologic screening for neurosyphilis].
AB  - BACKGROUND: Syphilis serology is analysed in all patients admitted as in-patients
      to the Department of Neurology in Tromso. In this study we examined the utility
      of performing routine laboratory testing for syphilis in neurological patients.
      MATERIAL AND METHODS: We registered all in-patients in the Department of
      Neurology with a confirmed diagnosis of syphilis during a ten-year period (1990
      1999). Additionally, we calculated the cost of performing laboratory tests of all
      hospitalised patients in this period. RESULTS: From a total of 8,637 patients, we
      identified five patients with syphilis, one of them with neurosyphilis. This
      patient had impaired cognitive functions at the time of admittance and a broad
      spectrum of neurological deficits suggesting a serious neurological disease. A
      positive syphilis serology confirmed the diagnosis and treatment was initiated.
      The mean cost for Treponema pallidum serological screening in neurological
      patients during 10 years was calculated to be about NOK 17,000 per year.
      INTERPRETATION: Tertiary syphilis is a serious disease with symptoms often
      mimicking other diseases. Although the laboratory tests for syphilis have been
      performed in every in-patient admitted to the neurological ward, a speedier
      diagnosis of neurosyphilis could not be detected in any patient in a ten-year
      hospital material. Routine serological examination for syphilis in neurological
      patients is therefore not recommended in this geographical area.

PMID- 11301699
TI  - [Perforated ulcer].
AB  - BACKGROUND: We wanted to review patients operated for perforated peptic ulcer at
      Ulleval University Hospital, Oslo, Norway in the period 1992-1997. MATERIAL AND
      METHODS: Data from 84 operated patients (43 men) were obtained retrospectively
      from patient and hospital files. Median age was 69 years (range 20-92 years).
      RESULTS: 41 patients had perforated duodenal ulcer and 43 had perforated gastric
      ulcer (pylorus included). Median time from start of symptoms until admission to
      hospital was 5 hours (range 2-24 hours; n = 40) and from admission to start of
      surgery 5 hours (range 1 1/2-48 hours; n = 69). 64 out of 74 patients had
      pneumoperitoneum on preoperative abdominal X-ray examination. 77 patients were
      operated with rafi and/or tegmentation of the perforation; six patients with
      Billroth II or Billroth I; one patient was treated with percutaneous drainage.
      Median duration of surgery was 68 minutes (range 40-240 minutes). Thirteen
      patients died in hospital. Post-operative complications were recorded in 30
      patients. INTERPRETATION: Early surgical intervention is important to reduce
      lethality from ulcus perforatum. A patient with clinical peritonitis and
      suspected perforated peptic ulcer should be operated without time-consuming
      examinations.

PMID- 11301700
TI  - [Severely injured patients after the initial phase--vegetative state or remaining
      cognitive functions?].
AB  - BACKGROUND: We wanted to quantify improvements in the subacute rehabilitation
      phase in patients with severe brain injuries classified as vegetative or minimal
      brain consciousness. MATERIAL AND METHODS: Five patients were studied during a 12
      months period using a method called Coma Recovery Scale (CRS) as described by
      Giacino et al. (1991). The parameters measured included visual and hearing
      functions, motor functioning, oromotor/verbal function, communication, and
      arousal. The observations of the patients and commandos given were standardised
      in a manual, and the responses achieved from the patients were recorded according
      to a scale for each parameter. RESULTS: This procedure for measuring closely the
      progress over time in these severely brain injured patients, was used for
      planning a realistic rehabilitation program. It was found to be very practical in
      communication with relatives of the patients and with the other therapists
      involved. INTERPRETATION: By decomposing the cognitive functions by this method
      using all the available possibilities for inputs, even minimal improvement in the
      cognitive functions mentioned could be uncovered and recorded.

PMID- 11301701
TI  - [Neuromuscular complications of sepsis].
AB  - BACKGROUND: Neuromuscular complications are common in patients treated for sepsis
      and multiple organ dysfunction in critical care units. Failure to wean from the
      ventilator, due to involvement of the respiratory system, and severe muscular
      weakness are typical symptoms. Electrophysiological examination demonstrates
      fibrillation potentials and reduction of compound muscular action potential
      amplitudes. MATERIAL AND METHODS: We report three patients with severe muscular
      weakness during treatment of critical illness. RESULTS: Critical illness
      polyneuropathy was the main cause of weakness in two patients, with a presumed
      superimposed myopathy in one. A third patient had critical illness myopathy.
      INTERPRETATION: Critical illness polyneuropathy and myopathy--either as separate
      or combined entities--are common causes of muscular weakness during treatment of
      critical illness. These disorders are often difficult to distinguish from each
      other, as the clinical and electrophysiological findings may overlap. Sepsis and
      multiple organ dysfunction are the main aetiological factors, but certain drugs
      may contribute in the pathogenesis. No specific treatment exists. In the most
      severe cases long-lasting physiotherapy and rehabilitation is needed.

PMID- 11301702
TI  - [Neuromuscular complications of myxoma].
AB  - BACKGROUND: Myxomas are the most common type of primary cardiac tumours. As they
      are most often located in the left atrium, primary neurological manifestations
      are often multiple embolic infarcts in the central nervous system. MATERIAL AND
      METHODS: We describe a patient with acute aphasia due to left temporal
      haemorrhage. Later he developed acute ataxia due to right cerebellar infarct.
      RESULTS: Magnetic resonance also showed multiple supra- and infratentorial
      infarcts. Echocardiography revealed a myxoma in the left atrium which was treated
      by surgical excision. There were no signs of myxoma recurrence or embolic
      infarcts at follow-up. INTERPRETATION: Echocardiography should be included in the
      diagnostic work-up of patients with cerebrovascular events, especially in young
      patients with multiple infarcts.

PMID- 11301703
TI  - [Human granulocytic ehrlichiosis in Norway].
AB  - BACKGROUND: The bacterium that causes human granulocytic ehrlichiosis may be
      transmitted by ticks. MATERIAL AND METHODS: We describe two patients with human
      granulocytic ehrlichiosis. During the summer of 1998, both patients were bitten
      by ticks. Four to 7 days later they developed influenza-like symptoms with fever,
      headache and myalgia. After 4 and 21 days, respectively, both patients were given
      doxycycline for suspected bacterial respiratory diseases, and recovered. RESULTS:
      Blood samples for human granulocytic ehrlichiosis antibodies showed a fourfold
      increase in titer in one patient and a remaining high titer in the other. Both
      patients had a positive polymerase chain reaction with primers specific for the
      Ehrlichia phagocytophilae genogroup. INTERPRETATION: The two patients fulfill the
      human granulocytic ehrlichiosis diagnostic criteria set by Centers for Disease
      Controls and Prevention, and are the first two human granulocytic ehrlichiosis
      cases described in Norway.

PMID- 11301704
TI  - [Tick-borne encephalitis in Norway].
AB  - BACKGROUND: Tick-borne encephalitis is caused by a virus that is transmitted to
      man by tick-bite. The virus is found in central and eastern parts of Europe and
      also in Sweden. MATERIAL AND METHODS: We report the first two cases of tick-borne
      encephalitis resulting from transmission of virus in Norway. RESULTS: Both
      patients had been to the island of Tromoy on the south coast of Norway. The
      course of the disease was very different in the two patients. One patient had
      significant neurological dysfunction. The other patient had intense headache, but
      no motor dysfunction. Both patients had reduced general health and fever, and
      leukocytosis and increased protein was found in the spinal fluid. The incubation
      period is most often 1 to 2 weeks. The disease may have a bi-phasic course with
      initial fever, headache and muscle pain. One week later symptoms of encephalitis
      follow. Subclinical infection is common, especially in children. One third of
      patients get permanent sequelae after encephalitis. Diagnosis is made by
      demonstration of antibodies in serum. Treatment is symptomatic. INTERPRETATION:
      These two patients indicate that there may be a reservoir of TBE virus in Norway.

PMID- 11301705
TI  - [Abbreviated surgical stay programs--a professional and administrative
      challenge].
AB  - Accelerated surgical stay programs represent a multi-modal, multi-disciplinary
      concept to reduce postoperative morbidity, hospitalisation and convalescence
      based upon recent advantages in surgical pathophysiology and pain treatment.
      Preliminary data from a variety of surgical procedures suggest major improvements
      in quality of surgical care and cost reduction and call for further controlled or
      large-size multicenter studies.

PMID- 11301706
TI  - [Distribution of left ventricular output].
AB  - BACKGROUND: This survey focuses on distribution of cardiac output to various
      organs and on some dynamic changes occurring in cardiac output and its
      distribution. MATERIALS AND METHODS: Data presented are largely related to work
      carried out in our research group, where Doppler ultrasonography is widely used
      for measurement of cardiac output and arterial blood flow. Additional data are
      drawn from relevant literature, in part compiled through search in the PubMed
      database. DATA AND INTERPRETATIONS: The difference in blood flow to various
      organs is emphasised, with e.g. brain and endocrine organs receiving large and
      stable blood supplies, whereas inactive muscles are sparsely perfused. Attention
      is drawn to distribution patterns in situations where cardiac output is markedly
      increased. Such situations are muscular exercise, with a dramatic increase in
      muscle blood flow, the occurrence of bodily heat surplus, with increased skin
      blood flow, and the postprandial situation, with augmented blood flow to the
      gastrointestinal tract. Of particular interest are situations where two or more
      demands for increased blood supply occur simultaneously, such as muscular
      exercise in the period just after a meal. Physically trained persons are
      apparently better than others at maintaining gastrointestinal blood supply during
      exercise.

PMID- 11301707
TI  - [Metabolic errors in newborn infants--diagnosis and treatment].
AB  - Different symptoms and clinical signs of metabolic disease in the neonatal period
      are reviewed. Initial laboratory studies dealing with critically ill neonates are
      recommended. Different biochemical findings are commented and linked towards the
      most probable diseases. Finally, treatment in the acute phase of disease is
      presented.

PMID- 11301708
TI  - [Infections and use of antibiotics in nursing homes].
AB  - BACKGROUND: The number of elderly people is constantly increasing in the western
      world. Many of these elderly spend their last years in a nursing home. Long-term
      care residents frequently have infections. However, there is only limited
      knowledge with regard to the spectrum of infections and the usage of antibiotics
      in nursing homes, in Norway and also in other European countries. MATERIAL AND
      METHODS: Prevalence of infections, risk factors related to infections and
      antibiotic usage were studied in four nursing homes in Baerum county. RESULTS: Of
      all 262 nursing home residents, 8.4% had an infection; 3.4% received antibiotic
      treatment. 66% of residents were more than 80 years old, 98% had a private room.
      Of all residents 3.4% had a urinary tract infections, 1.9% a skin infection, 1.1%
      a respiratory tract infection, and 1.9% an eye infection. 42% of all residents
      were treated with psychopharmacological drugs. 3.9% had an urinary catheter, and
      11% skin ulcers. INTERPRETATION: Our study did not discover any extraordinary
      problems with infections or antibiotic overuse in the nursing homes investigated.
      However, further studies are warranted in order to learn more about this issue in
      these institutions, which may represent an important but frequently
      underestimated source of resistant bacteria in a community.

PMID- 11301709
TI  - [Magnus Haaland--a pioneer in international cancer research].
AB  - Pathologist and bacteriologist Magnus Haaland (1876-1935) was a pioneer in
      European experimental cancer research. For eight years he worked in some of the
      most prominent research institutions in France, Germany and England. He worked
      with Elie Metschnikow and Amedee Borrel at Institut Pasteur in Paris, with Paul
      Ehrlich in Frankfurt am Main and with Erwin Bashford at the Imperial Cancer
      Research Fund in London. From 1911 to his death in 1935, he was the head of the
      Gade Institute in Bergen. He became a pioneer in Norwegian bacteriology research
      and made particular contributions to the eradication of typhoid fever in Norway.
      His main scientific work was on the progression of experimental transplantable
      tumours in mice, patterns of metastasis, and experimental hyperthermia treatment.
      He gave the first description of neoplastic reticuloses in mice.

PMID- 11301710
TI  - [Treatment with antiepileptic agents in patients with mental retardation and
      multiple handicaps].

PMID- 11301711
TI  - [Asthma--a condition of our time, a condition in change?].
AB  - BACKGROUND: This article reviews causative factors for asthma and allergy during
      childhood and describes current trends in prevalence and hospitalisation for
      childhood asthma. MATERIALS AND METHODS: A review of the prevalence of childhood
      asthma in Norway over the last 50 years together with recent trends in
      hospitalisation for childhood asthma, is given. Possible causative factors for
      childhood asthma are reviewed, and recent theories for the current increase in
      prevalence are discussed. RESULTS AND INTERPRETATION: During the last 50 years, a
      steady increase in the prevalence of childhood asthma has been documented through
      published studies from 1948 and onwards. From 1980 and until 1990, an increase in
      hospital admissions due to acute asthma was observed; later, admissions have
      leveled off, particularly as regards readmissions. Smoking during pregnancy and
      childhood decreases lung function. Allergic sensitisation is related to asthma
      development and may occur already during pregnancy. Increased allergic
      sensitisation may occur due to reduced load of infections. However, respiratory
      virus infections, and especially RS virus and rhinovirus infections, are closely
      related to asthma development and symptoms during childhood. A reduction in
      readmissions for asthma may be related to increased use of antiinflammatory
      therapy for asthma.

PMID- 11301712
TI  - [Development of infectious diseases--a consequence of differences?].

PMID- 11301713
TI  - [Reversibility testing with oxis].

PMID- 11301714
TI  - [How big is the editorial freedom?].

PMID- 11301715
TI  - [About virility research and advertising].

PMID- 11301716
TI  - [Criticism of the "blood group diet"--science or rage?].

PMID- 11301717
TI  - [Transcendental meditation and substance addiction].

PMID- 11301718
TI  - Papules near the eye. Yellow-white lesions on the eyelid may indicate an
      underlying clinical condition.

PMID- 11301720
TI  - Our prevention dilemma.

PMID- 11301719
TI  - Peripheral arterial disease. Medical management in primary care practice.
AB  - Peripheral arterial disease (PAD) is caused by atherosclerosis, the leading cause
      of death and disability in patients age 50 and older. PAD progresses gradually
      and silently over many years, occluding the lumen of arteries that supply blood
      to the extremities. Symptoms of peripheral arterial insufficiency include
      intermittent claudication, rest pain, and impotence. Nonoperative management-
      including the control of risk factors such as hypertension, diabetes,
      hyperlipidemia, and smoking--is the most effective method to lower the risk of
      morbidity from PAD. Diagnostic technologies such as color duplex imaging, MRI,
      and MRA complement the clinical assessment of PAD and provide a stronger
      foundation for treatment decisions in the primary care setting.

PMID- 11301721
TI  - Prostatitis. Work-up and treatment of men with telltale symptoms.
AB  - Prostatitis describes a spectrum of disorders involving inflammation of the
      prostate gland. This common yet poorly understood condition produces an array of
      symptoms, the most common of which are urinary obstruction, perineal pain, and
      ejaculatory complications. Although several theories have been proposed regarding
      its etiology, the exact mechanism of disease remains elusive. Definitive
      diagnosis can be hampered by a somewhat cumbersome testing procedure, but
      symptomology tends to be a reliable guide for treatment. Although treatment with
      antibiotics often fails, the fluoroquinolones are among the most effective agents
      for symptom management. Other interventions that may be appropriate include alpha
      1-adrenergic blockers, a 5-alpha reductase inhibitor, or surgery. Chronic
      prostatitis may result in repeated urinary tract infections and chronic pain
      syndromes.

PMID- 11301722
TI  - Preventive medicine. When to screen for disease in older patients.
AB  - Goals for health promotion and disease prevention in older patients include
      reducing premature mortality caused by chronic and acute illnesses, maintaining
      functional independence, extending life expectancy, and maintaining or enhancing
      quality of life. Determining whether a screen or intervention is warranted
      depends upon several key factors: whether the disease or condition will
      significantly impact a patient's quality of life, whether acceptable methods of
      treatment are available, and implications of delaying treatment. Although most
      diseases progress insidiously and undetected, there is a window of opportunity
      for screening and prevention during the asymptomatic phase. Some of the most
      effective interventions involve lifestyle changes such as smoking cessation and
      regular physical activity.

PMID- 11301723
TI  - Creativity with aging: four phases of potential in the second half of life.

PMID- 11301724
TI  - Is it Alzheimer's? Neuropsychological testing helps to clarify diagnostic puzzle.
AB  - This patient displayed a pattern of neuropsychological test results that
      indicated early Alzheimer's dementia. Using neuropsychological testing to make
      the diagnosis provided an answer for the patient, family, and psychiatrist, who
      all recognized a problem, and allowed for future planning. Recommendations for
      the patient included: psychoeducation and support for the patient and family
      assistance with planning for the future, including discussions of advance
      directives and financial management re-evaluation of the patient's ability to
      drive a motor vehicle a trial of a cholinesterase inhibitor such as donepezil or
      rivastigmine ongoing health maintenance, including periodic screening for
      depression and other psychiatric symptoms repeat neuropsychological assessment in
      6 months to 1 year to assess rate of decline and confirm the diagnosis.

PMID- 11301725
TI  - [The influence of visualization of orthography on the recognition of written
      words].
AB  - This paper reviews the main research that has been conducted on the role of
      orthographic neighbourhood in visual word recognition. We focus here on the
      traditionally defined neighbourhood, that is corresponding to the set of words of
      the same length sharing all but one letter with the stimulus. Two major
      theoretical frameworks, namely the activation verification and the interactive
      activation models, assume that orthographic neighbours are activated when a
      written word is presented. Predictions formulated by both models for words and
      pseudowords on the effects of neighbourhood size (N), neighbourhood frequency
      (NF), and neighbourhood distribution (P), are examined in order to assess the
      plausibility of serial versus interactive processes. Findings from 27 empirical
      studies including more than 80 experiments suggest that neighbourhood effects
      depend on the neighbourhood indexes (N, NF, and P), on the particular tasks
      (lexical decision, naming, semantic categorization, perceptual identification,
      and reading), and on the languages (English, French, Spanish, and Dutch) that are
      used. The results for words can be summarized as follows: (1) In the lexical
      decision task, the N effect is facilitatory. The NF effect is rather inhibitory,
      particularly in French and Spanish experiments. The P effect is rather inhibitory
      in English studies, whereas the P effect for higher frequency neighbours is
      facilitatory in French. (2) In the perceptual identification task with a single
      identification response, N and NF effects are inhibitory whatever the language.
      (3) In the naming task, N and NF effects are facilitatory whatever the language.
      (4) In the semantic categorization task, an interaction effect between N and NF
      is found in both English and Spanish. (5) In eye movement studies, the NF effect
      is inhibitory in both English and French. The issue of lexical versus task
      specific processes underlying neighbourhood effects in lexical identification
      tasks is also examined. On the whole, facilitatory N effects are usually
      attributed to nonlexical processes of the lexical decision task and of the naming
      task, whereas inhibitory neighbourhood frequency effects are usually attributed
      to lexical processes, at least in lexical-decision experiments and in eye
      movement studies on normal reading. The distribution of higher frequency
      neighbours which is found to have a facilitatory effect on French words in
      lexical-decision experiments can be attributed to lexical processes in the
      interactive activation framework. The theoretical implications of the data are
      discussed in light of the original activation verification and interactive
      activation models and in recently extended versions of these models. We conclude
      that the lexical inhibition hypothesis which is central in the interactive
      activation framework is the most appropriate to account for the role of
      orthographic neighbourhoods in visual word recognition.

PMID- 11301726
TI  - Negative priming for spatial location?
AB  - The term negative priming has been used to describe the deleterious consequences
      for performance when the current target shares properties with an ignored
      distractor from the previous trial. Location-based negative priming was first
      reported by Tipper, Brehaut, and Driver (1990) who used a prime-probe procedure
      wherein the task was to localize targets defined by their identity (shape).
      Design imbalances in this seminal study, and others, are illustrated and it is
      indicated how these might have contaminated the reported effects. The findings,
      from three experiments using an unbiased design, suggest that negative priming in
      the spatial location procedure may be more closely related to inhibition of
      return (IOR), or to the automatic attraction of attention by new objects, than to
      the concepts of distractor inhibition, episodic retrieval, and feature mismatch,
      which have traditionally been used to explain negative priming for spatial
      location.

PMID- 11301727
TI  - The influence of symbolic literacy on memory: testing Plato's hypothesis.
AB  - The present study examined the influence of the production of external symbols on
      memory strategies. Plato hypothesized that dependency on writing as an external
      memory store would be deterimental to memory. Three experiments were conducted to
      explore this hypothesis. Participants played Concentration, a memory game where
      players must find matching pairs of cards placed face down in an array.
      Participants were allowed to make notes to aid their performance under some
      experimental conditions, while under other conditions they could not. In
      Experiments 1 and 2, the unexpected removal of participants' notes revealed that
      the performance benefit was due to notes acting as a form of external memory
      storage, rather than as an aid to encoding information in memory. Experiment 3
      qualified these findings by demonstrating that the identity of each card was
      retained in memory, while the location of each card tended to be stored in the
      participants' external notations. These data suggest a modified interpretation of
      Plato's hypothesis in that symbolic literacy may change how we remember
      information. Rather than storing all information in memory, we only have to
      retain the information necessary to use the much larger storage capacity of the
      external system. Thus, the introduction of external symbols allows for a change
      in how memory is adaptively distributed.

PMID- 11301728
TI  - Reading both high-coherence and low-coherence texts: effects of text sequence and
      prior knowledge.
AB  - Previous research (e.g., McNamara, Kintsch, Songer, & Kintsch, 1996) has
      demonstrated that high-knowledge readers learn more from low-coherence than high
      coherence texts. This study further examined the assumption that this advantage
      is due to the use of knowledge to fill in the gaps in the text, resulting in an
      integration of the text with prior knowledge. Participants read either a high- or
      low-coherence text twice, or they read both the high- and low-coherence texts in
      one order or the other. Reading the low-coherence text first should force the
      reader to use prior knowledge to fill in the conceptual gaps. However, reading
      the high-coherence text first was predicted to negate the necessity of using
      prior knowledge to understand the low-coherence text when the latter was
      presented second. As predicted, high-knowledge readers benefited from the low
      coherence only text when it was read first. Low-knowledge readers benefited from
      the high-coherence text, regardless of whether it was read first, second, or
      twice.

PMID- 11301729
TI  - Basic processes in reading: semantics affects speeded naming of high-frequency
      words in an alphabetic script.
AB  - Previous work on single-word naming in university-level readers has shown that
      semantic factors affect the naming of low frequency words both in an alphabetic
      script like English, which is often irregular in terms of the spelling-sound
      correspondences, and in the syllabic Japanese Kana script, in which the spelling
      sound correspondences are consistent. The present experiment shows that a
      semantic factor (imageability) affects naming time to both low- and high
      frequency words in an alphabetic script (Persian) when the word is opaque (vowels
      not specified) but not when it is transparent (vowels specified). Other
      characteristics of opaque words that promote the use of semantics are discussed.
      At least in some orthographies, semantics play a larger role in single-word
      naming than previously thought.

PMID- 11301730
TI  - Belief-based and covariation-based cues affect causal discounting.
AB  - Causal discounting occurs when the perceived efficacy of a putative cause is
      reduced by the presence of a stronger causal candidate. Previous studies of
      causal discounting have defined the strength of causal candidates in terms of the
      degree to which the cause and the effect covary (e.g., Baker, Mercier, Vallee
      Tourangeau, Frank, & Pan, 1993). In contrast, in the present study, causal
      strength was defined in terms of both covariation- and belief-based cues. Seventy
      two participants made causality judgments for a fictional causal candidate both
      in isolation and when paired with either a stronger or a weaker cause. The
      results demonstrated that the degree to which a causal candidate is discounted
      depends not only on the degree to which an alternative cause covaries with the
      effect, but also on whether the alternative is a believable or unbelievable
      candidate. Indeed, it was observed that a highly believable alternative will
      produce the discounting effect, even if it is a weaker covariate than the
      original candidate. These findings suggest the need to incorporate both belief
      based and covariation-based cues into models of causal attribution.

PMID- 11301731
TI  - This article provides a brief summary of all voluntary adverse experience reports
      received by the National Registration Authority for Agricultural and Veterinary
      Chemicals (NRA) during 1999.

PMID- 11301732
TI  - Holistic vets must prove their treatments.

PMID- 11301733
TI  - CSIRO shows macropods unlikely hosts for JE.

PMID- 11301734
TI  - Balanced hen debate.

PMID- 11301735
TI  - Where were you when we needed you?

PMID- 11301736
TI  - Proxy hen vote urged.

PMID- 11301737
TI  - No more patients?

PMID- 11301738
TI  - To 'e' or not to 'e'.

PMID- 11301739
TI  - Petline working well.

PMID- 11301740
TI  - Food safety and housing.

PMID- 11301741
TI  - Breeder stops docking!

PMID- 11301742
TI  - Ocular discharge and eyelid swelling in a cat.

PMID- 11301743
TI  - Granulosa cell tumour in two speyed bitches.
AB  - Granulosa cell tumours are uncommon ovarian tumours in the bitch and are rare in
      speyed bitches. This case report describes two cases of granulosa cell tumour in
      bitches that were speyed at less than 1-year-of-age. Both animals presented with
      persistent vulval bleeding. Although the majority of granulosa cell tumours are
      large enough to be palpated by the time of presentation, both tumours were
      relatively small. Granulosa cell tumour is a possible complication of incomplete
      ovarian excision at the time of ovariohysterectomy. In cases of granulosa cell
      tumour in previously speyed bitches, with no evidence of metastases, tumour
      resection should be curative. Ovaries should be double-checked at the initial
      ovariohysterectomy to ensure all normal ovarian tissue has been excised.

PMID- 11301744
TI  - Diagnosis and management of cor triatriatum dexter in a Pyrenean mountain dog and
      an Akita Inu.
AB  - Cor Triatriatum Dexter is a rare, congenital cardiac defect in which the right
      atrium is partitioned into two compartments, effectively creating a triatrial
      heart. The clinical signs exhibited by the patient usually relate to impeded
      venous return via the caudal vena cava. The two dogs in this report both
      displayed ascites from a young age and grew poorly. In both cases the diagnosis
      was made during echocardiographic examination and was confirmed by angiography.
      Both dogs were successfully treated by resection of the partitioning membrane
      within the right atrium, using hypothermia and inflow occlusion to achieve a
      clear surgical field. Both dogs recovered well, their clinical signs resolved and
      they have grown to normal adult size.

PMID- 11301745
TI  - Feline polycystic kidney disease in Persian and other cats: a prospective study
      using ultrasonography.
AB  - OBJECTIVE: To determine the prevalence of feline polycstic kidney disease in
      Persian cats presented to the University of Melbourne Veterinary Clinic and
      Hospital between February and August 1999. DESIGN: A prospective clinical study
      using client owned animals was performed. PROCEDURE: Two hundred and fifty
      Persian cats, ranging in age from 13 weeks to 10 years, were presented to the
      University of Melbourne Veterinary Clinic and Hospital for ultrasound examination
      of both kidneys. The cats were placed in dorsal and lateral recumbency and
      alcohol and ultrasonic coupling gel were applied to the skin. The kidneys were
      examined ultrasonographically in longitudinal, sagittal and transverse planes.
      Results were recorded for each cat at the time of examination as either negative
      or positive for PKD. In addition 14 Exotics (short-haired Persians), 4 Ragdolls
      and 3 British Short-Hair cats were examined. RESULTS: Forty five percent of
      Persian cats examined were found to be positive for feline polycystic kidney
      disease on the basis of presence of anechoic cysts within the renal parenchyma.
      These cats ranged in age from 13 weeks to 10 years. Fifty per cent of the Exotic
      cats were positive for polycystic kidney disease whereas all Ragdolls and British
      Short Hairs were negative for the disease. Only one positive cat was reported to
      be showing clinical signs of renal disease. CONCLUSION: The prevalence of feline
      polycstic disease in Persian cats presented to the University of Melbourne
      between February and August 1999 was 45%. Exotic cats were found to have the
      slightly higher incidence of 50%.

PMID- 11301746
TI  - Calcinosis circumscripta following an injection of proligestone in a Burmese cat.
AB  - A 9-month-old speyed Burmese cat was presented with a cutaneous lesion in the
      dorsal thoracolumbar region. The lesion was characterised by alopecia and whitish
      deposits within the subcutis and had occurred at the site of a previous
      progestogen injection (Covinan; Intervet). Excisional biopsy confirmed the
      diagnosis of calcinosis circumscripta. Recovery of the cat following surgical
      excision was excellent, with no recurrence of the lesion detected 12 months
      later. The classification of tissue calcification and the proposed aetiology of
      calcinosis circumscripta is reviewed. It is concluded that further work is
      required to determine any link between subcutaneous injections, especially of
      progestogens, and calcinosis circumscripta.

PMID- 11301747
TI  - Identification and eradication of Menangle virus from pigs.

PMID- 11301748
TI  - Reproductive disease and congenital malformations caused by Menangle virus in
      pigs.
AB  - OBJECTIVE: To describe a new syndrome characterised by embryonic mortalities,
      stillbirths, mummified foetuses and congenital malformations in a herd of
      intensively farmed pigs. DESIGN: Field observations, laboratory investigations
      and examination of breeding records. PROCEDURE: Pathology examinations were
      performed on mummified and congenitally deformed piglets during an outbreak of
      reproductive disease at a 2600 sow intensive piggery in New South Wales from
      April to October 1997. Reproductive performance was monitored during the outbreak
      and breeding records were examined retrospectively. Serum and tissue samples from
      pigs were tested for evidence of infection with known porcine pathogens and for a
      new virus, Menangle virus, isolated from stillborn piglets with deformities from
      the affected piggery in August 1997. RESULTS: Reproductive disease occurred
      sequentially in all four breeding units at the affected piggery over a period of
      21 weeks. The farrowing percentages in each unit decreased from 80 to 82% before
      the outbreak to 63 to 78% during the outbreak and the number of live piglets per
      litter declined from a mean of 9.6 to 9.8 before the outbreak to 7.2 to 8.9
      during the outbreak. The proportion of affected litters (litters with less than
      six liveborn piglets) was highest (64%) in the sixth week of the outbreak.
      Mummified foetuses, stillborn piglets with arthrogryposis, craniofacial
      deformities and degeneration of the brain and spinal cord, were observed along
      with occasional abortions. Sera from sows that produced affected litters
      contained neutralising antibodies against Menangle virus and there was evidence
      that this virus had been introduced to the piggery in February 1997. CONCLUSIONS:
      Reproductive disease in pigs due to Menangle virus was characterised by
      stillbirths, mummification, embryonic death and infertility, along with
      abortions, skeletal deformities and degeneration of the brain and spinal cord in
      affected foetuses and stillborn piglets.

PMID- 11301749
TI  - Epidemiology and control of Menangle virus in pigs.
AB  - OBJECTIVE: To describe the epidemiology and eradication of Menangle virus
      infection in pigs. DESIGN: Field observations and interventions, structured and
      unstructured serological surveys, prospective and cross-sectional serological
      studies and laboratory investigations. PROCEDURE: Serum samples were collected
      from pigs at a 2600-sow intensive piggery in New South Wales that experienced an
      outbreak of reproductive disease in 1997. Serum samples were also collected from
      piggeries that received pigs from or supplied pigs to the affected piggery and
      from other piggeries in Australia. Serum and tissue samples were collected from
      pigs at piggeries experiencing reproductive disease in New South Wales. Sera and
      faeces were collected from grey-headed flying foxes (Pteropus poliocephalus) in
      the region of the affected piggery. Serum samples were tested for neutralising
      antibodies against Menangle virus. Virus isolation was attempted from faeces.
      RESULTS: Following the outbreak of reproductive disease, sera from 96% of adult
      pigs at the affected piggery, including sows that produced affected litters,
      contained neutralising antibodies against Menangle virus. Neutralising antibodies
      were also detected in sera from 88% of finisher pigs at two piggeries receiving
      weaned pigs from the affected piggery. No evidence of Menangle virus infection
      was found in other piggeries in Australia. In cross-sectional studies at the
      affected piggery, colostral antibodies were undetectable in most pigs by 14 to 15
      weeks of age. By slaughter age or entry to the breeding herd, 95% of pigs
      developed high antibody titres (> or = 128) against Menangle virus in the virus
      neutralisation test. Menangle virus was eradicated from the affected piggery
      following a program of serological testing and segregation. Neutralising
      antibodies against Menangle virus were also detected in P poliocephalus from two
      colonies in the vicinity of the affected piggery. Two piggery workers were
      infected with Menangle virus. There was no evidence of infection in cattle,
      sheep, birds, rodents, feral cats and a dog at the affected piggery. CONCLUSIONS:
      Serological evidence of infection with Menangle virus was detected in pigs at a
      piggery that had experienced reproductive disease, in pigs at two associated
      piggeries and in fruit bats in the region of the piggery. Two humans were
      infected. The mode of transmission between pigs is unknown, but spread by faecal
      or urinary excretion is postulated. This virus can be eradicated by the
      segregation of pigs into discrete age groups.

PMID- 11301750
TI  - Combined xylazine and ketamine as an analgesic regimen in sheep.
AB  - OBJECTIVE: To determine whether low dose xylazine with ketamine reduces the
      concentrations of cortisol and prolactin in sheep postoperatively and to
      characterise the effects of the drugs on behaviour during recovery. DESIGN:
      Analysis of variance was used to compare the effects of anaesthesia, surgery and
      combined ketamine/xylazine treatment on the plasma cortisol and prolactin
      concentrations and on behavioural variables in pregnant ewes subjected to
      abdominal surgery. PROCEDURE: Twelve ewes were randomly assigned to receive
      either ketamine/xylazine or placebo in association with anaesthesia and surgery.
      Both groups of ewes underwent anaesthesia alone followed a week later by
      anaesthesia with laparotomy and hysterotomy. Plasma cortisol and prolactin
      concentrations were assayed during these procedures and for 5 days afterwards.
      Behavioural observations were made remotely during recovery from anaesthesia and
      anaesthesia plus surgery. RESULTS: The concentrations of cortisol in the plasma
      of pregnant ewes undergoing surgery were increased by preoperative handling and
      the onset of thiopentone/halothane anaesthesia, with a further increase during
      surgery (P = 0.033). Cortisol concentrations decreased over the first four
      postoperative hours (P = 0.029) and were normal by 24 h. The drug treatment did
      not affect the immediate responses of ewes to anaesthesia or surgery, although
      treated ewes had lower cortisol concentrations than saline-treated controls over
      the first five postoperative days (P = 0.018). Prolactin concentrations increased
      in response to anaesthesia (P = 0.047), but were not affected by surgery or the
      drug treatment. Drug-treated ewes had prolonged sleeping time after surgery (P =
      0.002), but they took no longer to stand than saline-treated controls and
      required fewer attempts to stand successfully (P = 0.025). CONCLUSION: At the
      doses used, ketamine and xylazine did not mitigate the immediate endocrine
      consequences of surgery but the behavioural data provide a basis for further
      investigations that may lead to improvements in analgesic treatments.

PMID- 11301751
TI  - Algal infection in sheep grazing irrigated pasture.

PMID- 11301752
TI  - The media. More than ethics on trial.

PMID- 11301753
TI  - Is it all black magic?

PMID- 11301754
TI  - Thyroid hormone in depression.

PMID- 11301756
TI  - Managing scaphoid fractures--which one is right?

PMID- 11301758
TI  - Depression in men.
AB  - BACKGROUND: The suicide rate is five times higher for men compared with that for
      women, yet the rate of depression is twice as great in women compared with men.
      Men are less likely than women to present to their doctors with concerns about
      physical and psychological problems. Men seem to be more vulnerable to becoming
      depressed in the context of social and economic change compared with women.
      OBJECTIVE: To raise awareness regarding detection and treatment of depression in
      men in a primary care setting. DISCUSSION: General practitioners are ideally
      suited to diagnose and treat depression early. By increasing GPs' awareness of
      depression, utilising screening instruments in everyday clinical practice, and
      having psychoeducation materials available, GPs can help to destigmatise and
      effectively treat depression in men. Encouraging men to talk about their problems
      with the use of open ended questions and engaging a partner or family member
      helps to encourage treatment adherence.

PMID- 11301759
TI  - Cardiovascular disease & depression.
AB  - BACKGROUND: Risk factor reduction may present a strategy for preventing
      depression. Risk factors for depression include cultural, social and personality
      as well as biochemical and pharmacological factors. Patients with cardiovascular
      disease have a high prevalence of depression. Depressed patients with
      cardiovascular disease have worse outcomes than other patients. OBJECTIVES: To
      review the literature on depression in patients with cardiovascular disease,
      focusing on strategies to reduce the impact of this dual pathology. DISCUSSION:
      Several mechanisms may explain the high prevalence of depression in patients with
      cardiovascular disease, and why these patients experience worse outcomes. There
      is little evidence about the effectiveness of mental health promotion and illness
      prevention strategies for patients with cardiovascular disease. Implementation
      and evaluation of trial programs such as community mental health promotion,
      support groups, individual counselling, and treatment with psychotherapy and
      medication, will demonstrate which strategies are effective.

PMID- 11301760
TI  - Are doctors immune to depression?
AB  - BACKGROUND: Depression is common in the Australian community. Doctors are not
      immune to depression and in fact are at increased risk. OBJECTIVE: To discuss
      specific issues for depressed doctors, barriers to appropriate care and treatment
      and prevention strategies. DISCUSSION: Doctors have specific risks for depression
      related to personality traits, coping styles and work stresses. The stigma of
      mental illness affects doctors as much as other members of the community.
      Appropriate self care, cultural change within the medical profession, training
      for doctors in the care of other doctors and health promotion strategies are
      required.

PMID- 11301761
TI  - Management of deep vein thrombosis.
AB  - BACKGROUND: Deep vein thrombosis is a common condition which may occur
      spontaneously or after surgery. Recently, there has been an increased
      understanding of its causes and risk factors. OBJECTIVE: To outline the aims of
      treatment which are initially to prevent pulmonary embolism and further
      recurrence of the thrombosis. The initial treatment involves administration of
      unfractionated heparin or low molecular weight heparin. DISCUSSION: The
      development of the low molecular weight heparin makes treatment at home a
      possibility. Warfarin is also started within 24-hours and its dose adjusted to an
      international normalised ratio of 2-3. In most patients, the oral anticoagulant
      therapy should continue for 3-6 months, or longer in those with recurrent venous
      thromboembolism and those with acquired or hereditary prothrombotic states.

PMID- 11301762
TI  - Designing a consumer friendly practice.
AB  - BACKGROUND: With the threat of corporate practice looming, smaller private
      general practices need to define their role in order to attract patients
      (consumers) and doctors, to build and maintain a successful practice. OBJECTIVE:
      To outline various means of instituting a consumer friendly practice. DISCUSSION:
      Consider what consumers want. Bearing in mind these aims, build the physical
      aspects of your practice to respond to the needs of consumers, and develop
      practice activity, philosophy and culture which satisfy the desires of consumers
      and those of the doctors and staff who work in your practice. Creating a consumer
      friendly practice attracts patients, Practice Incentive Payments, and prepares
      for accreditation. By developing such a culture, general practitioners can build,
      support and maintain the practice style they prefer, even in the face of
      competition.

PMID- 11301763
TI  - An unusual presentation of fatal invasive meningococcal disease.

PMID- 11301764
TI  - The herbal basis of some gastroenterology therapies.
AB  - This is the fourth in a series of articles discussing herbal therapies. This
      month looks at the herbal basis of gastrointestinal tract therapies. Disorders of
      digestion and bowel movement have troubled mankind throughout recorded time,
      providing a steady workload for herbal and orthodox practitioners. Most of these
      problems are mild and many herbs are used to treat the resulting minor symptoms
      with varying degrees of success.

PMID- 11301765
TI  - A technique for ankle dysfunction.

PMID- 11301766
TI  - Herb-drug interaction guide.
AB  - Herbal medicines now fall into the category of complementary medicines.  With
      their increasing popularity, a new set of circumstances has arisen--the herb-drug
      interaction.  In an effort to streamline the interaction information available,
      the author has designed two charts.  The first lists the 21 most popular herbal
      medicines sold in Australia, sourced from the largest natural supplement
      manufacturer in Australia, Bullivant Natural Health Products.  The second lists
      the 12 commonly prescribed prescription drug classes.  This list was sources from
      F H  Faulding & Co Ltd, together with Austrialian Prescriber.  Specific
      interaction information was collated from a variety of sources-- medical and
      complementary medicine journals, pharmacy practice journals and respected
      phytotherapy tests. These tables are excerpts from these charts.

PMID- 11301767
TI  - Casting acute fractures. Part 6--The Colles slab.
AB  - BACKGROUND: Colles fractures are common in our ageing population. Safety
      maintaining reduction with a fully split encircling cast is time and labour
      intensive. This article explores a near encircling slab as a simpler alternative.
      OBJECTIVE: The specific technique for the application of a strong slab likely to
      safely maintain reduction is demonstrated. Correct moulding techniques and
      position are emphasised. DISCUSSION: Maintenance of reduction of these fractures
      is important for final outcome. Slight rather than marked palmar flexion is a
      significant change in current practice improving outcome. Closure of this slab at
      follow up can convert it quickly and cheaply to a definitive encircling cast.

PMID- 11301768
TI  - Radiology quiz. Right iliac fossa pain.
AB  - A 70 year old woman with a history of severe emphysema presents with a one week
      history of progressively worsening right iliac fossa pain, anorexia and right
      lower quadrant tenderness.

PMID- 11301769
TI  - Deep vein thrombosis and air travel.
AB  - Mary is a 55 year old woman on hormone replacement therapy. She is flying to the
      UK with her husband in a few weeks time, and is concerned about the recent media
      attention given to the 'economy class syndrome'. Mary's sister developed a
      similar problem after surgery some years ago. She is worried that she might be at
      risk of developing a clot during her flight and asks your advice.

PMID- 11301770
TI  - Ethical principles. Conflict or cooperation?

PMID- 11301772
TI  - To err is human....

PMID- 11301771
TI  - Sick doctors. A personal story.

PMID- 11301773
TI  - Assessment of depression in older adult males by general practitioners. Ageism,
      physical problems and treatment.
AB  - BACKGROUND: Depressive symptoms are common among older people. This study
      evaluated whether the combination of age and the presence of a physical illness
      would influence the recognition, treatment and further investigation by general
      practitioners of possible depression in older adult males. METHOD: A 2 x 2
      factorial design involving four vignettes of a male with depression was used. The
      variables involved two age levels and the presence or absence of heart disease.
      The sample consisted of 189 Perth GPs. RESULT: Depression was recognised by up to
      95% of the GPs. Although the recognition of uncomplicated depressive symptoms was
      lower in the 76 year old male compared with the 56 year old, health recognition
      seemed the same for both. There were no effects for recommended treatment,
      prognosis, perceived competency to treat or further investigation. Antidepressant
      medication and counselling by the GP were the recommended treatments. CONCLUSION:
      Depressive symptoms were recognised by more GPs in this study than in the
      existing literature, but with less likelihood of recognition for the older male.

PMID- 11301774
TI  - Making mistakes in practice. Developing a consensus statement.
AB  - OBJECTIVE: To develop a reference statement for the appropriate management of
      mistakes in the general practice training environment. METHOD: The setting was a
      series of focus groups held during workshops with The Royal Australian College of
      General Practitioners Training Program in the Northern Territory (NT). The
      participants included NT supervisors and registrars, and representatives of the
      Consumer Reference Group, Top End Division of General Practice. RESULTS: A
      reference statement and mutually agreed list of duties for registrars, their
      supervisors and patients. CONCLUSION: Mistakes are a part of the practice of
      medicine and can impact on everyone. An appropriate response and the opportunity
      to reflect and learn from the experience are important elements in minimising the
      adverse impact. We recommend that the issue of mistakes be considered a priority
      in the teaching of medicine.

PMID- 11301775
TI  - Changing GPs' clinical behaviour. What can divisions do?
AB  - BACKGROUND: The increasingly complex challenge for medical practitioners to keep
      up to date and use the best available evidence in their clinical decision making
      has led to important studies on the effectiveness of various strategies to change
      clinician behaviour. Divisions of General Practice can develop an evidence based
      framework to support this change. OBJECTIVE: The aims of this paper are to:
      discuss effective interventions to change clinicians' behaviour describe the
      theories which underlie these strategies suggest a framework for Divisions of
      General Practice to design and implement effective programs. DISCUSSION:
      Continuing medical education and guideline implementation serve to highlight the
      impact of various change strategies. The interventions and the theories that
      underlie them, whether they be from a social, behavioural or organisational
      perspective, offer Divisions of General Practice an opportunity to support GPs in
      their ongoing professional need for quality improvement.

PMID- 11301776
TI  - [Injected feces--burned scan--arm constriction. What some patients do to
      themselves (interview by Petra Eiden)].

PMID- 11301777
TI  - [Recurrent headache, without apparent cause. Masked depression].

PMID- 11301778
TI  - [Acute therapy of stroke. With these basic measures prognosis can be improved].
AB  - Up until a few years ago, the acute management of stroke generated a massive
      sense of nihilism. Since then, things have changed drastically. In the first
      place, systemic thrombolysis for infarctions in the anterior cerebral circulation
      is now approved in Germany--although a number of questions still remain
      unanswered. In the second place, the consequences of a stroke can be effectively
      mitigated by the rapid application of apparently commonplace "basic measures".
      These include the maintenance of a "high/normal" blood pressure, control of
      respiratory function with aspiration prophylaxis, securement of normal glycemia,
      optimization of cardiac output and microcirculation, lowering of elevated
      temperatures, and relief of increased intracerebral pressure, if necessary via a
      craniotomy. As required by the stroke unit concept--which is now widely
      established--rapid referral of the patient, and interdisciplinary management by
      an experienced team is of decisive importance for the prognosis.

PMID- 11301780
TI  - [Emergencies in general practice, 6. Acute abdomen].

PMID- 11301779
TI  - [Patient with suspected apoplexy. A case for the stroke unit?].
AB  - Stroke units are monitoring centers providing for acute diagnostic work-up,
      immediate treatment and initial rehabilitation measures in patients suffering a
      stroke. Indications for admission to a stroke unit are, firstly, a suspected
      fresh stroke or a transient ischemic attack, provided the symptoms are not older
      than 24 hours, and, secondly, progressive, unstable symptoms. A major aspect of
      the stroke unit is the establishment of a differential diagnosis, which provides
      the basis for establishing the urgent treatment of an apoplectic attack. The goal
      is to prevent the progression of symptoms, which occurs in one-third of patients
      and leads to permanent sequelae. Using a number of cases, the activities of a
      stroke unit are described. To improve the acute management of such patients, a
      close network of regional and national stroke units needs to be put in place.

PMID- 11301781
TI  - [Acid, abrasion, toxin injection... How facial wrinkles are smoothed out].

PMID- 11301782
TI  - [Compliance in hypertension therapy. What works in "forgetfulness"?].

PMID- 11301783
TI  - [Diagnosis and therapy of post-traumatic stress disorder. Helping to cope with
      memories].

PMID- 11301784
TI  - [The new EBM 2000 plus before the evaluation committee. Table of contents remains
      -but content is missing].

PMID- 11301785
TI  - [Despite ongoing epidemic. Preventive influenza vaccination is still of value].

PMID- 11301786
TI  - [Stress-induced hypertension. The work site--a cardiovascular risk].

PMID- 11301787
TI  - Mixed bag in Medicare trustees' report.

PMID- 11301788
TI  - Frist seeks CAP compromise.

PMID- 11301789
TI  - We're back, says Tauzin.

PMID- 11301790
TI  - Perspectives. Time is money: admin simplification on hold?

PMID- 11301791
TI  - Bolster quality efforts by developing effective PI (performance improvement)
      infrastructure.
AB  - Every hospital in the country today is engaged in performance improvement
      programs in one form or another. But industry consultant Michelle Pelling, RN,
      MBA, president of the Propell Group in Portland, OR, warns that many quality
      improvement directors embark on these projects without first gaining support from
      physicians and staff, and without having in place an effective infrastructure to
      bolster their efforts.

PMID- 11301792
TI  - Learn how to measure PI (performance improvement) across departments.
AB  - While focusing on the overall outcome of a performance improvement initiative is
      important, the involvement of individual departments is critical when it comes to
      how their processes contribute to achieving performance expectations, experts
      say. It is often less a linear process than it is an ongoing cycle.

PMID- 11301793
TI  - 'The rest of the iceberg': IOM looks at quality.
AB  - The Institute of Medicine's Committee on Quality of Healthcare in America
      released a sweeping 300-page report March 1 that claims fundamental changes are
      needed in the American health care system if 'the quality gap' that currently
      exists is to be eliminated. In his introductory remarks, committee chair William
      Richardson said the IOM's previous report on medical errors, the controversial To
      Err Is Human, represented 'the tip of the iceberg. Other defects beyond safety
      are even more widespread'.

PMID- 11301794
TI  - Initiative cuts ED visits, hospital admissions.

PMID- 11301795
TI  - Referrals ensure continuum of care.

PMID- 11301796
TI  - How to apply Y2K lessons to patient confidentiality.
AB  - Despite current debate over the details of implementing the privacy portion of
      the Health Insurance Portability and Accountability Act (HIPAA) of 1996, experts
      say quality managers should continue their planning to comply with the new law.
      One way to prepare for the sweeping new mandates is to apply the lessons of Y2K
      to HIPAA.

PMID- 11301798
TI  - JCAHO patient safety standards stress leadership.

PMID- 11301797
TI  - Equipment-related errors in the workplace.
AB  - Health care practitioners must know how to operate a wide array of machines. With
      the growing number of complex medical devices, equipment-related patient
      incidents are on the rise. Equipment problems are a frequent cause of untoward
      events.

PMID- 11301799
TI  - Medication study may bolster compliance.

PMID- 11301800
TI  - After the "nitroglycerin truck": hospital-physician relations in the "post
      integration" era.

PMID- 11301801
TI  - Back to the fifties: refocus on the medical staff.

PMID- 11301802
TI  - Medical economics in the millennium: working longer, lower take-home pay.

PMID- 11301803
TI  - Hospital-physician relations in the millennium: no more "holding hands and
      jumping off a cliff".

PMID- 11301804
TI  - The return of Darling. Jones v. Chicago HMO Ltd.

PMID- 11301806
TI  - Virginia provision addresses provider panel participation issue.

PMID- 11301805
TI  - Patient wins hollow victory on contract claim. Dingle v. Belin.

PMID- 11301807
TI  - Playing with pain killers.

PMID- 11301808
TI  - How one town got hooked.

PMID- 11301809
TI  - Even my husband never knew.

PMID- 11301810
TI  - Recommended schedules for routine immunization of children and adults.
AB  - Vaccine recommendations continue to evolve as a result of new vaccines, safety
      considerations, changing disease incidence (e.g., polio), and public health
      priorities. The pace of discovery is accelerating and advisory committees will
      need to respond accordingly. Each vaccine, new or old, will be required to earn
      its place in the routine immunization schedule on the basis of public health
      benefit or cost-benefit studies.

PMID- 11301811
TI  - Influenza vaccine: issues and opportunities.
AB  - Several recent developments offer opportunities to improve the diagnosis,
      treatment, and prevention of influenza. Rapid diagnostic tests assist in
      selecting patients for antiviral therapy and avoid some antibiotic use. The
      neuraminidase inhibitors now offer therapeutic options with potentially fewer
      side effects than the traditional drugs, albeit at greater cost. Inactivated
      influenza vaccine is now recommended annually for all persons aged 50 and older
      and younger adults and children (aged 6 months and older) who have underlying
      risk factors for the severe complications of influenza. This includes pregnant
      women who are in their second or third trimesters during influenza season.

PMID- 11301812
TI  - Issues related to the decennial tetanus-diphtheria toxoid booster recommendations
      in adults.
AB  - In terms of disease prevention, reduction of adverse reactions, and cost benefit
      studies, a strong case can be made for a policy that focuses on assuring high
      levels of primary immunization with tetanus and diphtheria (Td) toxoids and
      abandons the decennial Td booster in favor of a single midlife booster at age 50
      65 years. The addition of acellular pertussis antigens to Td for routine use in
      adults has potential problems in terms of schedule, cost, and possible adverse
      reactions. Careful risk/benefit studies are necessary to evaluate its
      effectiveness and priority.

PMID- 11301813
TI  - Meningococcal vaccines.
AB  - Global control and prevention of meningococcal disease depends on the further
      development of vaccines that overcome the limitations of the current
      polysaccharide vaccines. Protein-polysaccharide conjugate vaccines likely will
      address the marginal protective antibody responses and short duration of immunity
      in young children derived from the A, C, Y, and W-135 capsular polysaccharides,
      but they will be expensive to produce and purchase, and may not offer a practical
      solution to the countries with greatest need. In addition, OMP vaccines have been
      tested extensively in humans and hold some promise in the development of a
      serogroup B vaccine, but are limited by the antigenic variability of these
      subcapsular antigens and the resulting strain-specific protection. Elimination of
      meningococcal disease likely will require a novel approach to vaccine
      development, ideally incorporating a safe and effective antigen or antigens
      common to all meningoccocal serogroups. As a solely human pathogen, however, N.
      meningitidis has developed many tools with which to evade the human immune
      system, and likely will pose a formidable challenge for years to come.

PMID- 11301814
TI  - Lyme vaccine: issues and controversies.
AB  - The development of an effective vaccine for Lyme disease represents a major
      advance in the control of the most prevalent vector-borne disease in the United
      States. It has a definite place in the total approach to control of this disease.
      Its use should be restricted to individuals who are at moderate to high risk of
      exposure to infected vector ticks. Vaccinated individuals should not be
      complacent about other personal protection measures, because the vaccine is not
      uniformly effective and protective antibody levels decay rapidly. Booster doses
      will be necessary, but the intervals have not yet been determined. There is a
      theoretical concern about the possible induction of inflammatory arthritis
      through an autoimmune mechanism, but there is no evidence that this condition has
      clinical relevance. The impact of the current lawsuits on vaccine recommendations
      and use remains to be determined. Continued surveillance for rare long-term side
      effects should address the medical risk issue. Alternative primary vaccine
      administration schedules are currently under study, and could lead to regimens
      permitting achievement of protective immunity in 6 months or less. Vaccine is not
      approved for use in children under the age of 15 years.

PMID- 11301815
TI  - Rotavirus vaccine and intussusception. Where do we go from here?
AB  - Since the discovery of rotavirus in 1973, vaccine technology has moved from the
      use of monovalent attenuated animal rotavirus strains to the development of
      multivalent human-animal reassortment vaccines. The first licensed vaccine, a
      rhesus-human tetravalent vaccine, was licensed in 1998. This vaccine was
      withdrawn from the market a year later when it was noted that administration of
      vaccine was associated with an increased risk of intussusception. The future of
      rotavirus vaccine is dependent on the reasons for this association that have yet
      to be discovered.

PMID- 11301816
TI  - Combination vaccines.
AB  - The past decade has shown a marked increase in the number of vaccines currently
      licensed and recommended for use in infants and children. Although most agree
      that it is desirable to combine as many of these vaccines as possible into a
      single injection, safety and efficacy must not be sacrificed. Clearly, a
      resurgence in Hib meningitis or measles (for example) would not be an acceptable
      price for the convenience of a single injection; but it is not clear how large a
      reduction in immunogenicity can be incurred without paying such a price. This
      conundrum has slowed the licensure of useful combination vaccines, despite a
      consensus that parents and practitioners have reached a limit to the number of
      injections they will deliver to young children. We anticipate US licensure for
      infant use of (at least) one DTaP-IPV-Hib vaccine and one DTaP-IPV-HB vaccine
      within the next few years, given the apparent lack of material reduction in
      immunogenicity of these specific combination products. Licensure in the United
      States of some of the other combinations now used in Europe is also possible,
      given supporting national surveillance data or improvements in our understanding
      of the correlates of immunity. Enhanced vaccination tracking systems and
      postmarketing efficacy surveillance should provide confidence that material
      reductions in efficacy could be detected following licensure, and thereby ease
      the approval of combinations that result in moderate, but perhaps immaterial,
      declines in immunogenicity.

PMID- 11301817
TI  - Challenges and controversies in immunization safety.
AB  - No vaccine is perfectly safe or effective. As diseases such as diphtheria and
      polio fade, vaccine safety concerns, especially alleged links between
      vaccinations and several chronic illnesses, have become increasingly prominent in
      the media and to the public. This article reviews the current scientific evidence
      on several recent vaccine safety controversies. It also provides information on
      how various safety research is conducted, some of the concurrent challenges, and
      finally, some guidance on communicating with patients on vaccine risks.

PMID- 11301818
TI  - Travel-related vaccines.
AB  - Travelers are at increased risk for several infections, including familiar
      infections such as measles that are widely distributed but more common in
      developing countries. Vaccines can markedly decrease the risk for many of these
      infections and are an important part of pretravel preparation. Travel provides an
      opportunity to review and update routine vaccines in adults and assess risk from
      unusual infections. Global travel is growing. Persons who are elderly, HIV
      infected, and immunocompromised account for many of the travelers. Studies that
      assess the immunogenicity, efficacy, and adverse effects of some of the special
      vaccines used primarily in travelers generally have been done in young, healthy
      populations. Findings in young adults do not apply to other populations in whom
      immune response can be slower, less effective, and less durable. Recent reports
      of severe adverse events in elderly persons who have received yellow fever
      vaccine are a reminder that widely used, old vaccines can have unexpected side
      effects when used in a new population. It is biologically plausible that adverse
      effects might be more common in the elderly, and epidemiologically plausible that
      occasional instances of similar adverse events in the past could have been
      missed. Studies on special and travel vaccines in the elderly are needed urgently
      to define how these vaccines should be used in older populations and whether
      alternative means for protection are needed.

PMID- 11301819
TI  - Vaccines in pregnancy.
AB  - The concept of maternal immunization to prevent infectious diseases during a
      period of increased vulnerability in the infant is supported by historical
      experience and carefully conducted studies of various viral and bacterial
      vaccines. Candidate vaccines should be minimally reactogenic, immunogenic, and
      safe. Health education and access to immunization should be a priority if
      maternal immunization is to succeed as a disease prevention strategy. The
      potential effect on the incidence of disease in the newborn and young infant can
      only increase as more candidate vaccines that could be administered during
      pregnancy become available. In the future, common infections and other, more
      dreaded diseases, such as herpes simplex virus infection, cytomegalovirus, and
      human immunodeficiency virus infection, could be prevented with this
      intervention. Further research on the safety and efficacy of maternal
      immunization must continue if the occurrence of serious infectious diseases in
      neonates and young infants is to be reduced.

PMID- 11301820
TI  - Vaccines for transplant recipients.
AB  - Immune dysregulation and immunosuppression regimens impact on the ability of
      transplant recipients to respond to immunizations. The distinct challenges of
      immunizations to benefit stem cell transplant recipients and solid organ
      transplant recipients are discussed separately. Recommended vaccines for stem
      cell transplant recipients and solid organ transplant candidates are suggested.
      New approaches to consider to enhance immune responses of transplant recipients
      are discussed.

PMID- 11301821
TI  - Vaccines in the 21st century.
AB  - Steffens was wrong about the Soviet Union, and I may well be wrong about the
      future of vaccines; however, in Table 13, I give my [table: see text] prediction
      of the vaccination schedule of the next century. It is an optimistic vision, so
      let us hope that I am right.

PMID- 11301822
TI  - Poliomyelitis eradication: progress, challenges for the end game, and preparation
      for the post-eradication era.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally
      by the year 2000. Dramatic progress toward this goal has occurred: three of the
      six WHO regions (Region of the Americas, European Region, and Western Pacific
      Region) are now polio free; and the number of polio-endemic countries decreased
      from over 125 in 1988 to 30 in 1999. Intensified efforts currently are underway
      to reach the target as soon as possible after 2000 in the three remaining polio
      endemic WHO regions (African Region, Eastern Mediterranean Region, and South-East
      Asia Region). Even in polio-endemic regions, many countries are already polio
      free as the geographic extent of poliovirus shrinks while others. especially
      those experiencing conflict and war, pose substantial challenges to implementing
      the proven polio eradication strategies. Increasing attention and research now
      are devoted to the certification of polio eradication in the polio-free regions
      (that will include the first phase of implementing the Global Plan of Action for
      the laboratory containment of wild poliovirus) and formulating a policy for
      stopping all polio vaccination once eradication, containment, and global
      certification have been achieved. This report outlines the progress toward polio
      eradication and highlights some of the remaining issues and challenges that must
      be addressed before polio becomes a disease that future generations know only by
      history.

PMID- 11301823
TI  - Live-attenuated varicella vaccine.
AB  - This article reviews the history and development of live attenuated varicella
      vaccine from its early days in Japan to its widespread use throughout the world.
      The vaccine has proven extremely safe after immunization of as many as 10 million
      healthy children and adults in the United States alone. The vaccine is also
      highly immunogenic and offers close to 100% protection from severe chickenpox and
      90% protection from illness. It is expected to have a major impact on the
      epidemiology of varicella and zoster in countries with high vaccine uptake.

PMID- 11301824
TI  - Hepatitis vaccines.
AB  - The development of highly effective and safe inactivated HAV vaccines and highly
      effective and safe recombinant HBsAg subunit HBV vaccines represents major
      advances in the control of viral hepatitis, but many challenges remain. Because
      current HAV immunization recommendations target high-risk groups only, infection
      rates are unlikely to fall dramatically until universal childhood immunization
      programs are implemented. Routine HBV vaccination of infants, children,
      adolescents, and individuals at high risk will reduce the incidence of infection,
      but vaccine nonresponsiveness and escape mutants are important potential
      challenges. Whether either HAV or HBV vaccine provide lifelong protection remains
      to be determined. Vaccines for HDV, HEV, and HCV are not yet available.

PMID- 11301825
TI  - Standards for immunization practice for vaccines in children and adults.
AB  - Administration of vaccines is a continuing challenge. In childhood immunizations,
      many of the goals for national coverage rates by 2000 were achieved and the goal
      of annual influenza immunization for adults 65 years of age and older was
      reached. These successes in childhood immunization rates have led to record low
      numbers of cases of many vaccine-preventable diseases, such as measles and
      Haemophilus influenzae, type b invasive disease. These diseases will recur,
      however, as evidenced by the measles epidemic of 1989-1991, if high immunization
      coverage is not maintained. The development of immunization delivery systems to
      sustain these high rates in young children is essential to ensure that the 11,000
      infants born each day in the United States receive all recommended vaccines, as
      noted in the recent NVAC report on strategies to sustain success in childhood
      immunization. For adults, the total economic burden of treating these vaccine
      preventable diseases is estimated to exceed $10 billion each year, reflecting in
      part widespread underuse of vaccines in adults and resulting missed opportunities
      to prevent diseases such as influenza and pneumococcal infection. The development
      of standards for immunization practices in children and adults has been an
      important component in meeting these challenges and ensuring appropriate delivery
      of vaccines. Periodic review and updating is necessary and revision of the
      standards for adults by the NCAI and NVAC, pediatric standards, and those of the
      IDSA currently are undergoing revision. Most importantly, however, standards for
      immunization practices should be promulgated widely to all health care
      professionals to ensure that all segments of the population benefit from the
      availability of highly effective and safe vaccines.

PMID- 11301826
TI  - The prevention of pneumococcal disease by vaccines: promises and challenges.
AB  - This article reviews the epidemiology of pneumococcal disease and the current
      data on pneumococcal vaccine efficacy, discusses promising new data regarding
      development of new protein-conjugate pneumococcal vaccines, and addresses
      controversies surrounding the widespread population use of these vaccines. Armed
      with these data, physicians, nurses, third party payers, and health care systems
      should develop systems and eliminate unintentional barriers so as to achieve
      widespread use of these life-saving vaccines. As history has demonstrated to us,
      control of pneumococcal disease is highly unlikely to occur from heavy
      investments in newer and ever more expensive antibiotics, as opposed to better
      methods of preventing disease through the rational and widespread population use
      of vaccines.

PMID- 11301827
TI  - Trends in cigarette smoking among high school students--United States, 1991-1999.

PMID- 11301828
TI  - Systemic therapy for older women with breast cancer.
AB  - Breast cancer is a common problem in older women. As the number of medical
      illnesses increases with age and the life expectancy decreases, the benefits of
      systemic therapy for women with breast cancer become questionable. All women over
      age 65 years are at high enough risk of breast cancer to consider the
      risk/benefit ratio of preventive therapy with tamoxifen (Nolvadex) or
      participation in the Study of Tamoxifen and Raloxifene (STAR) trial. Adjuvant
      chemotherapy and hormonal therapies for early breast cancer significantly improve
      disease-free and overall survival; recommendations for their use are based on
      risk of tumor recurrence. Use of tamoxifen in the adjuvant setting in women with
      receptor-positive tumors is a relatively simple decision in light of its
      favorable toxicity profile. The delivery of adjuvant chemotherapy is a more
      complicated decision, and the patient's wishes, estimated life expectancy,
      presence of comorbid conditions, and estimated benefit from treatment should be
      considered. The primary goal of the treatment of metastatic breast cancer is
      palliation. We discuss trials specific to older women and make appropriate
      treatment recommendations. Unfortunately, there is a paucity of data from
      clinical trials in women over age 70 years. However, because the clinical trial
      is the primary scientific mechanism for testing the efficacy of a treatment,
      every effort should be made to enter older women into treatment protocols.

PMID- 11301829
TI  - Gene therapy for head and neck cancers.
AB  - Despite advances in surgery, radiotherapy, and chemotherapy, survival of patients
      with squamous cell carcinoma of the head and neck has not significantly improved
      over the past 30 years. Locally recurrent or refractory disease is particularly
      difficult to treat. Repeat surgical resection and/or radiotherapy are often not
      possible, and long-term results for salvage chemotherapy are poor. Recent
      advances in gene therapy have been applied to recurrent squamous cell carcinoma
      of the head and neck. Many of these techniques are now in clinical trials and
      have shown some efficacy. This article discusses the techniques employed in gene
      therapy and summarizes the ongoing protocols that are currently being evaluated
      in clinical trials.

PMID- 11301830
TI  - Clinical trials referral resource. Current clinical trials in small-cell lung
      cancer.

PMID- 11301831
TI  - Imaging prostate cancer: current and future applications.
AB  - Various treatment options are available for adenocarcinoma of the prostate--the
      most common malignant neoplasm among men in the United States. To select an
      optimum management strategy, we must be able to identify an organ-confined
      disease (in which local therapy such as surgery or radiation may be beneficial)
      vs prostate cancer beyond the confines of the gland (for which other treatment
      approaches may be more appropriate). At present, no standard imaging modality can
      by itself reliably diagnose and/or stage adenocarcinoma of the prostate. Standard
      transrectal ultrasound, magnetic resonance imaging (MRI), computed tomography,
      bone scans, and plain x-ray are not sufficiently reliable when used alone.
      Fortunately, advances in imaging technology have led to the development of
      several promising modalities. These modalities include color and power Doppler
      ultrasonography, ultrasound contrast agents, intermittent and harmonic ultrasound
      imaging, MR contrast imaging, MRI with fat suppression, MRI spectroscopy, three
      dimensional MRI spectroscopy, elastography, and radioimmunoscintigraphy. These
      newer imaging techniques appear to improve the yield of prostate cancer detection
      and staging, but are limited in availability and thus require further validation.
      This article reviews the status of current imaging modalities for prostate cancer
      and identifies emerging imaging technologies that may improve the diagnosis and
      staging of this disease.

PMID- 11301832
TI  - Empiric antifungal therapy for the neutropenic patient.
AB  - One of the major challenges facing oncologists today is invasive fungal
      infection. Difficult to diagnose and deadly when missed, invasive fungal
      infection--primarily by Candida and Aspergillus organisms--is the major
      infectious cause of death associated with chemotherapy-induced myelosuppression.
      In this review, the problem will be described and evidence-based approaches to
      management, including assessment for risk factors and empiric antifungal therapy,
      will be discussed. Finally, the future of diagnostic and therapeutic strategies
      for protecting the immunocompromised patient will be considered.

PMID- 11301833
TI  - Brachytherapy for carcinoma of the lung.

PMID- 11301834
TI  - Update on chemotherapy for advanced colorectal cancer.
AB  - Efforts to improve the length and quality of life, as well as to expand treatment
      options, for patients with metastatic colorectal cancer have only recently become
      more successful. With maximization of dose and schedule schemes for
      fluoropyrimidine therapy, new drugs such as irinotecan (CPT-11, Camptosar) and
      oxaliplatin have also become part of the standard therapy for patients.
      Combination chemotherapy has been established to have superior response rates and
      progression-free survival and--in some instances, for fluorouracil and irinotecan
      combinations--improved overall survival compared to fluorouracil alone. There is
      still much to be learned about the optimal management of patients with colorectal
      cancer, including the role of second- and third-line chemotherapy in the overall
      survival outcome, and the role of salvage therapy in patients with limited
      metastatic disease. Most importantly, the development of a biological marker of
      prognosis and response should help to select appropriate chemotherapy programs
      for patients on a rational and individual basis, not only in the setting of
      metastatic disease, but also in the adjuvant population.

PMID- 11301835
TI  - Current status of oral chemotherapy for colorectal cancer.
AB  - The treatment of advanced colorectal cancer over the past 4 decades has required
      the use of intravenous chemotherapy, most typically fluorouracil (5-FU). The
      possibility of providing an alternative to intravenous delivery while at the same
      time improving the quality of life of patients who require fluorouracil for
      advanced or adjuvant therapy has provided the stimulus for the development of
      oral fluoropyrimidine drugs. Five oral fluoropyrimidine drugs have recently
      entered clinical trials in the United States. These include capecitabine
      (Xeloda), UFT (uracil and tegafur) or UFT/leucovorin (Orzel), eniluracil
      (ethynyluracil), S-1, and BOF A-2. At least two of these drugs have demonstrated
      survival equivalent to the standard intravenous fluorouracil and leucovorin
      regimens used to treat advanced colorectal cancer. This, together with less
      severe toxicity and potential increased quality of life, should lead to approval
      of one or more of these oral agents in the near future. Based on both patient and
      physician acceptance of oral fluoropyrimidines, other oral drugs from classes
      other than fluoropyrimidines will likely be developed in the near future.

PMID- 11301837
TI  - New directions in the treatment of advanced colorectal cancer.
AB  - As the chemotherapy horizons have expanded in colorectal cancer with development
      of oxaliplatin (Eloxatin) and irinotecan (CPT-11, Camptosar), so too have our
      approaches to therapy. Numerous immunotherapy and gene therapy approaches are
      undergoing initial study. These methods are founded on increased knowledge of
      tumor biology. That same knowledge has led to the identification of new molecular
      targets for anticancer chemical therapies. This article highlights some of these
      developments with focus on epidermal growth factor receptor and angiogenesis.

PMID- 11301836
TI  - COX-2 inhibition in clinical cancer prevention.
AB  - Colorectal cancer is an excellent model for studying cancer prevention by means
      of secondary (e.g., polypectomy to remove a precursor adenoma) and primary
      (chemoprevention) strategies. Evidence has shown that regular users of aspirin
      and other nonsteroidal anti-inflammatory drugs (NSAIDs) have a reduction in risk
      of colorectal cancer. A possible mechanism of this benefit is decreased
      prostaglandin production, which is achieved through inhibition of cyclooxygenase
      (COX) activity, and possibly other pathways. Two isoforms of COX--COX-1 and COX-2
      -have been identified. COX-2 is expressed in colorectal adenomas and carcinomas,
      both in humans and rodents. Inhibition of COX-2 has been shown to decrease the
      incidence of carcinogen-induced neoplasia in rats and to lower the incidence of
      adenomas in murine models. Several COX-2 inhibitors, with the potential for less
      toxicity than that associated with traditional NSAIDs, are under development.
      This paper reviews potential chemoprevention of colorectal cancer using COX-2
      inhibitors in patients at increased risk, e.g., patients with familial
      adenomatous polyposis, hereditary nonpolyposis colorectal cancer, and sporadic
      adenomas. Included are the rationale for use of such agents, results of a study
      showing a significant reduction in adenoma burden in familial adenomatous
      polyposis patients who received the selective COX-2 inhibitor celecoxib
      (Celebrex), and the design of other ongoing or planned clinical trials.

PMID- 11301838
TI  - Future directions in adjuvant therapy for stage III colon carcinoma.
AB  - The current recommendation for adjuvant chemotherapy for patients with newly
      diagnosed stage III colon cancer involves 6 months of fluorouracil (5-FU) plus
      low- or high-dose leucovorin. In clinical trials performed throughout the world,
      several drugs have demonstrated either improved toxicity profiles or antitumor
      activity for patients with advanced colorectal carcinoma. Uracil and tegafur
      (UFT) and capecitabine (Xeloda) are two examples of new oral chemotherapy
      compounds with acceptable side-effect profiles in early adjuvant or advanced
      disease trials. Irinotecan (CPT-11, Camptosar) and oxaliplatin, when administered
      intravenously in combination with a 5-FU regimen, have both demonstrated
      significant antitumor effects for patients with advanced-stage disease. Other
      immunotherapies, including monoclonal antibodies and cancer vaccines, are being
      evaluated to help stimulate immune responses in patients with resected colon
      cancer. These agents are just a few examples of the new compounds being tested in
      the next generation of clinical trials for resected stage III colon cancer.
      Future and ongoing investigations will look to integrate these new therapies as
      we attempt to move beyond the era of 5-FU and leucovorin.

PMID- 11301839
TI  - Camptothecin schedule and timing of administration with irradiation.
AB  - The camptothecins are a new class of chemotherapeutic radiation sensitizers.
      Clinical trials with camptothecins alone show higher toxicity than predicted by
      preclinical models, which has created the challenge of finding new ways to widen
      the therapeutic window. Camptothecin dose, schedule, and timing with irradiation
      are important factors that need to be considered in the design of new studies
      with these S-phase agents. Data are reviewed from early phase I and II
      chemoradiation trials, including a multicenter, phase II study planned by the
      Radiation Therapy Oncology Group (RTOG) in operable rectal cancer using
      irinotecan (CPT-11, Camptosar). One novel approach (based on preclinical
      observations) with the potential to widen the therapeutic window may be the use
      of a chronomodulated camptothecin delivery schedule with irradiation.

PMID- 11301840
TI  - Cisplatin and irinotecan in upper gastrointestinal malignancies.
AB  - Irinotecan (CPT-11, Camptosar) a topoisomerase I inhibitor derived from the
      Chinese shrub Camptotheca acuminata, has broad activity in varied
      gastrointestinal malignancies, including pancreatic, biliary, esophageal, and
      stomach cancers. Using cisplatin (Platinol) plus irinotecan as a backbone for
      chemotherapy, a combination for which in vitro synergy and possible sequence
      dependency have been identified, several clinical trials are being conducted
      combining these two drugs with other chemotherapeutic agents and radiation. This
      article reviews a recently reported phase II study of cisplatin and irinotecan in
      esophageal cancer, and provides a preliminary report of two ongoing phase I
      studies of cisplatin/irinotecan/paclitaxel (Taxol); and
      cisplatin/irinotecan/fluorouracil (5-FU) in advanced gastrointestinal
      malignancies. Early results of an ongoing phase I study of cisplatin, irinotecan,
      and radiation in resectable and locally advanced unresectable esophageal cancer
      is also discussed. Preliminary data on all of these combinations suggest
      promising activity in upper gastrointestinal malignancies.

PMID- 11301841
TI  - Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer.
AB  - Gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar) are active cytotoxic
      drugs against pancreatic cancer. Preclinical data evaluating the combination of
      gemcitabine and irinotecan suggest dose-dependent synergistic interactions in
      SCOG small-cell lung cancer and MCF-7 breast cancer cell lines. Two phase I
      trials of this combination have been reported to date: the day 1 and 8 every-3
      week schedule (IrinoGem trial), and the day 1, 8, and 15 every-4-week schedule
      (MSKCC trial). Both trials aimed to determine the maximum tolerated dose of
      irinotecan when administered as a 90-minute i.v. infusion either immediately
      after (IrinoGem) or before or immediately after (MSKCC) gemcitabine at 1,000
      mg/m2 by 30-minute i.v. infusion in patients with solid tumors. The achieved
      maximum tolerated dose of IrinoGem has a higher dose intensity of irinotecan (100
      mg/m2 on days 1 and 8, every-3-week cycle) compared with the MSKCC schedule (60
      mg/m2 on days 1, 8, and 15, every-4-week trial). In IrinoGem, two of three
      previously untreated metastatic pancreas cancer patients had durable radiologic
      partial responses. The third had stable disease with clinical benefit for eight
      cycles. In addition, a patient with metastatic adenocarcinoma of unknown primary-
      potentially pancreatic--has had a durable response and is alive more than 30
      months after the diagnosis. Preliminary results of a 45-patient multicenter phase
      II trial with IrinoGem in advanced and metastatic pancreas cancer were recently
      reported. Toxicity was modest, with no toxic deaths or neutropenic fever.
      Radiologic response rate was 20% of patients (9 out of 45), and a CA 19-9
      decrease of more than 50% from baseline values occurred in 32.5% of patients (13
      out of 40). Median survival was 6 months (range: 0.9 to 12.2+ months) and median
      time to treatment failure was 2.9 months (range: 0.1 to 11.3+ months). A pivotal
      international multicenter phase III trial comparing IrinoGem to single-agent
      gemcitabine in advanced and metastatic pancreas cancer is ongoing.

PMID- 11301842
TI  - Irinotecan plus cisplatin in advanced gastric or gastroesophageal junction
      carcinoma.
AB  - A phase II study was conducted to assess the response rate and toxicity profile
      of the combination of irinotecan (CPT-11, Camptosar) and cisplatin (Platinol)
      administered weekly to patients with untreated advanced adeno-carcinoma of the
      stomach or gastroesophageal junction. Patients with histologic proof of
      adenocarcinoma of the stomach or gastroesophageal junction and with adequate
      liver, kidney, and bone marrow functions were included. Patients were treated
      with 65 mg/m2 of irinotecan plus 30 mg/m2 of cisplatin, both administered
      intravenously 1 day per week for 4 consecutive weeks, followed by a 2-week
      recovery period. Response rate, time to progression, survival, and toxic effects
      were analyzed. Thirty-six (95%) of 38 registered patients were assessable for
      toxicity and response. The median number of 6-week cycles per patient was 2.5
      (range: 1 to 7 cycles). Four patients (11%) achieved a complete response and 17
      (47%) had a partial response for an overall response rate of 58%. Median time to
      progression of carcinoma was 24 weeks, and median survival was 9 months (range: 1
      to 23+ months). There was one treatment-related death. Major toxic effects
      included diarrhea, neutropenia, and fatigue. The combination of irinotecan and
      cisplatin is active against gastric or gastroesophageal adenocarcinoma and should
      undergo further study. The addition of other active drugs or radiation therapy to
      this regimen would be of interest.

PMID- 11301843
TI  - Gemcitabine in combination with new platinum compounds: an update.
AB  - Combinations of gemcitabine (Gemzar) with cisplatin (Platinol) are among the most
      active new chemotherapy regimens developed for advanced non-small-cell lung
      cancer. Carboplatin (Paraplatin) is a platinum analog devoid of many of the
      nonhematologic toxicities associated with cisplatin. Although few direct
      comparisons have been made, when administered by area under the concentration
      time curve (AUC) dosing, carboplatin is probably equivalent to cisplatin in
      advanced non-small-cell lung cancer and provides an improved therapeutic index.
      Based on its favorable toxicity profile, carboplatin has supplanted cisplatin for
      use in combination with paclitaxel in several different tumor types. Initial
      trials combining gemcitabine and carboplatin using standard days 1, 8, and 15
      dosing of gemcitabine suggested that thrombocytopenia was problematic. More
      recently, 21-day schedules in which gemcitabine is administered only on days 1
      and 8 have demonstrated both efficacy and improved toxicity profiles. Here we
      review recent studies investigating gemcitabine plus carboplatin and preliminary
      data regarding combinations of gemcitabine with the new platinum analog
      oxaliplatin.

PMID- 11301844
TI  - Gemcitabine and nonplatinum combinations in non-small-cell lung cancer.
AB  - Gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), and vinorelbine
      (Navelbine) are among the most active agents for the treatment of non-small-cell
      lung cancer and are generally more active than platinum compounds. When combined
      with a platinum compound, these agents have produced the best survival outcomes
      seen to date in non-small-cell lung cancer. More than 100 clinical trials have
      defined and expanded the role of gemcitabine, which has been combined with each
      of these agents to create novel combinations. Several new nonplatinum-based
      combinations compare favorably with platinum-based combinations with respect to
      toxicity and efficacy. Moreover, changing the schedule of gemcitabine
      administration from days 1, 8, 15 every 4 weeks to days 1 and 8 every 3 weeks
      seems to allow greater dose intensity with less severe toxicity and slightly
      greater efficacy. Coadministration of docetaxel, paclitaxel, or vinorelbine with
      gemcitabine on days 1 and 8 every 3 weeks is a promising approach. In addition to
      a lower incidence of severe neutropenia, docetaxel, paclitaxel, and vinorelbine
      protect against gemcitabine-associated thrombocytopenia.

PMID- 11301845
TI  - Triplet combination chemotherapy and targeted therapy regimens.
AB  - Current agents for the treatment of non-small-cell lung cancer include
      gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), vinorelbine
      (Navelbine), and irinotecan (CPT-11, Camptosar). Experimental agents include
      pemetrexed (LY231514, Alimta) and tirapazamine. Molecular and biological
      therapies include angiogenesis inhibitors, epidermal growth factor receptor
      inhibitors, HER2/neu inhibitors, and inhibitors of ras activation and function.
      Doublet chemotherapy is currently the standard treatment for advanced non-small
      cell lung cancer. In the past 2 years, randomized trials have shown that many of
      the new two-drug combinations used to treat non-small-cell lung cancer have
      equivalent efficacy. These combinations produce 1-year survival rates of about
      35% and 2-year survival rates of about 15%. Toxicity rates vary but are
      sufficiently low as to make the development of three-drug combinations feasible.
      Preliminary studies from several phase I and II trials suggest that triplet
      therapy can improve survival beyond that of double therapy regimens.

PMID- 11301846
TI  - Gemcitabine for the treatment of non-small-cell lung cancer.
AB  - Platinum-based chemotherapy regimens have been the mainstay of treatment for non
      small-cell lung cancer because they improve survival. Although there is no
      standard platinum-based regimen, combination regimens with newer agents (e.g.,
      gemcitabine [Gemzar], paclitaxel [Taxol], and vinorelbine [Navelbine]) are
      superior to platinum alone or in combination with older agents (e.g., etoposide).
      Four phase III clinical studies demonstrate the favorable activity and toxicity
      profile of gemcitabine in combination with cisplatin (Platinol) for the treatment
      of patients with stage IIIB or IV non-small-cell lung cancer. These studies show
      overall response rates of approximately 30% to 60% with gemcitabine regimens
      versus overall response rates of 11% with cisplatin alone, 22% with cisplatin
      plus etoposide, 25% with cisplatin plus vinorelbine, and 40% with cisplatin plus
      mitomycin and ifosfamide (Ifex). Median survival time with gemcitabine regimens
      ranged from 8.1 to 9.8 months. Thrombocytopenia and anemia are the principal
      toxicities with gemcitabine regimens. Because of the favorable results with
      gemcitabine regimens, this drug is being evaluated in combination with
      carboplatin (Paraplatin) in newly diagnosed patients with stage IIIB or IV
      disease and good performance status, or as single-agent therapy in patients with
      poor performance status.

PMID- 11301847
TI  - Gemcitabine and cisplatin combination in early-stage non-small-cell lung cancer.
AB  - A number of randomized clinical trials now support the conclusion that the
      combined-modality regimen that includes gemcitabine (Gemzar) and cisplatin
      (Platinol) may improve survival in disseminated non-small-cell lung cancer.
      Cisplatin is considered to be the "backbone" of this combination chemotherapy due
      to its proven activity. The regimen of gemcitabine and cisplatin has been tested
      and is now considered among the most active combinations in the treatment of
      disseminated non-small-cell lung cancer.

PMID- 11301848
TI  - Optimizing chemoradiation in locally advanced non-small-cell lung cancer.
AB  - Gemcitabine (Gemzar) has demonstrated activity in a broad range of solid tumors
      with good tolerance. In combined-modality therapy, gemcitabine has achieved
      response rates ranging between 30% and 60% in patients with non-small-cell lung
      cancer. Initial trials of gemcitabine and radiation showed that the fields and
      volume of radiation as well as the dose of gemcitabine should be managed
      carefully so as to optimize the radiosensitizing properties of this agent. The
      Cancer and Leukemia Group B conducted a phase III trial in patients with
      unresectable stage III non-small-cell lung cancer. A total of 187 patients were
      randomized to one of three cisplatin (Platinol)-based combinations (with
      gemcitabine, paclitaxel [Taxol], or vinorelbine [Navelbine]) as induction therapy
      followed by concomitant chemoradiation. At a median follow-up of 9 months, the
      median survival for all patients was 18 months and the median progression-free
      survival was 10 months. The trial demonstrated that the combination of
      gemcitabine and cisplatin could be administered successfully as induction therapy
      without affecting concurrent administration of gemcitabine/cisplatin with
      radiation.

PMID- 11301849
TI  - Treatment of elderly patients with non-small-cell lung cancer.
AB  - One of the main reasons for the increased acceptance of chemotherapy for both
      early and advanced non-small-cell lung cancer is the clinical availability of
      several new cytotoxic drugs. These less toxic, yet highly effective, new drugs
      not only benefit younger patients, but also offer new treatment opportunities for
      the elderly; advanced age alone should not preclude appropriate cytotoxic
      therapy. Vinorelbine (Navelbine) was the first new agent tested in randomized
      trials with elderly patients having advanced non-small-cell lung cancer. Results
      proved that vinorelbine does indeed have a survival advantage over best
      supportive care for these patients. Gemcitabine (Gemzar) is probably the most
      effective cytotoxic agent in the treatment of non-small-cell lung cancer today,
      showing high antitumor activity as a single agent and in combination. Moreover,
      it has a favorable toxicity profile. Since it can be effectively used for the
      palliation of tumor-related symptoms and can thus positively influence
      performance status, gemcitabine may be of great clinical importance in the
      treatment of elderly and unfit patients. Docetaxel (Taxotere) has recently become
      the first agent to be registered for second-line chemotherapy in non-small-cell
      lung cancer. This decision was based on survival advantages and clinical benefit
      data stemming from two randomized phase III studies. Nonetheless, chemotherapy
      for elderly patients continues to be a major unresolved oncologic problem.
      Clinical research with the new cytotoxic agents should be intensified to further
      define the most appropriate use for these drugs as single agents or in
      combination for the treatment of elderly patients.

PMID- 11301850
TI  - Novel approaches in the treatment of non-small-cell lung cancer.
AB  - A wealth of data indicates that certain genetic abnormalities can target specific
      cytotoxic drugs and intervene at an early step as a mechanism of resistance in
      the treatment of non-small-cell lung cancer. Therefore prescribing certain
      combinations of cytotoxic anticancer agents to a vast majority of these patients
      is futile. Genetic abnormalities have been found to be useful surrogate markers
      for response, particularly in colorectal cancer: thymidylate synthase mRNA and
      ERCC1 mRNA levels. In addition, beta-tubulin mutations may also confer paclitaxel
      resistance in patients. An important target to be explored for gemcitabine
      resistance is the assessment of a particular region in chromosome 11p15.5 wherein
      lies the ribonucleotide reductase gene that could affect gemcitabine metabolism.
      Shedding light on this genetic framework, several proposed customized
      chemotherapy studies could help validate the relevance of these markers.

PMID- 11301851
TI  - State of the art of non-small-cell lung cancer in the new millennium.

PMID- 11301852
TI  - A sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-kappa
      B by targeting I kappa B phosphorylation.
AB  - A sesquiterpene lactone, costunolide (CTN), was identified from Magnolia
      grandiflora together with parthenolide (PTN) by its strong inhibition of LPS
      induced NF-kappa B activation. CTN, which showed more potent inhibition than PTN
      in the NF-kappa B activation, strongly suppressed nitric oxide (NO) production in
      LPS-stimulated RAW 264.7 cells. RT-PCR and Western blot analyses demonstrated
      that CTN suppressed the expression of iNOS mRNA and protein in a dose-dependent
      manner. CTN also significantly inhibited LPS-induced DNA-binding activity of NF
      kappa B as well as the LPS-induced degradation of I kappa B-alpha and -beta.
      Furthermore, CTN inhibited LPS-induced phosphorylation of I kappa B-alpha. These
      findings support that CTN inhibits NO production by down-regulating iNOS
      expression, at least, in part through the inhibition of I kappa Bs'
      phosphorylation and degradation, which are essential for the activation of NF
      kappa B.

PMID- 11301853
TI  - Influence of natural and synthetic compounds on cell surface expression of cell
      adhesion molecules, ICAM-1 and VCAM-1.
AB  - Various natural and synthetic compounds including alkaloids, terpenoids and
      phenolics were tested for inhibition of the cell surface expression of
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1), both of which are crucial in the regulation of immune response and
      inflammation. Of 40 compounds tested, two compounds significantly downregulated
      the expression of VCAM-1 on murine endothelial cells (F-2) and ten compounds that
      of ICAM-1 on mouse myeloid leukemia cells (M1). Sanguinarine chloride (5) and
      isoliquiritigenin (13) were capable of lowering the levels of both ICAM-1 and
      VCAM-1. The structure-activity relationships study on chalcone and flavone
      derivatives related to 13 suggested that the inhibitory activity of the chalcone
      derivatives is attributable to the 4-hydroxy group as well as the possible
      coplanarity between the phenyl ring and the adjacent conjugated ketone.

PMID- 11301854
TI  - Structure-antinociceptive activity studies of incarvillateine, a monoterpene
      alkaloid from Incarvillea sinensis.
AB  - Incarvillateine (1), a new monoterpene alkaloid carrying a characteristic
      cyclobutane ring, has been found to show significant antinociceptive activity in
      a formalin-induced pain model in mice. To investigate the correlation between its
      structure and antinociceptive activity, and especially to study whether a
      cyclobutane ring is necessary or not for expression of activity, we evaluated the
      antinociceptive activity of two constructive units of incarvillateine, such as a
      monoterpene unit (incarvilline, 3) and a phenylpropanoid unit (ferulic acid, 2)
      in the formalin test, and compared activity of the units with that of
      incarvillateine. Furthermore, in order to obtain more information about the
      structure-activity relationships, monoterpene alkaloid derivatives, such as
      incarvine C (5, a precursor of incarvillateine), incarvine A (4, an ester
      compound comprised of two monoterpene alkaloids and a monoterpene) and 3,3'
      demethoxy-4,4'-dehydroxyincarvillateine (6, a synthetic new compound), were
      examined. The antinociceptive effect of 3,3'-demethoxy-4,4'
      dehydroxyincarvillateine was equal to that of incarvillateine. Meanwhile, the
      other compounds exhibited no or weak activity. These results suggested that the
      cyclobutane moiety of incarvillateine plays an important role in expression of
      antinociceptive action.

PMID- 11301855
TI  - Kalopanaxsaponin A is a basic saponin structure for the anti-tumor activity of
      hederagenin monodesmosides.
AB  - Hederagenin, delta-hederin [hederagenin alpha-L-arabinoside], kalopanax-saponin A
      [hederagenin 3-O-alpha-L-rhamnosyl(1-->2)-alpha-L- arabinoside], kalopanaxsaponin
      I [hederagenin 3-O-beta-D-xylosyl(1-->3)-alpha-L- rhamnosyl(1-->2)-alpha-L
      arabinoside], and sapindoside C [hederagenin 3-O-beta-D-glucosyl(1-->4)-beta-D
      xylsyl (1-->3)-alpha-L-rhamnosyl(1-->2)-alpha-L-arabinoside] were isolated from
      stem bark of Kalopanax pictus Nakai (Araliaceae). Among glycosides of
      hederagenin, disaccharide (kalopanaxsaponin A, commonly also called alpha
      hederin), trisaccharide (kalopanaxsaponin I), and tetrasaccharide (sapindoside C)
      showed significant cytotoxicity on several types of tumor cells, while
      hederagenin itself exhibited only weak cytotoxicity and its monosaccharide (delta
      hederin) was non-cytotoxic. From these results, it suggests that the arabinosyl
      moiety at C-3 blocks the activity of hederagenin and the position of the second
      sugar for glycoside linkage is also important for cytotoxicity. In the in vivo
      experiments, kalopanaxsaponin A (15 mg/kg, i.p.) apparently increased the life
      span of mice bearing Colon 26 and 3LL Lewis lung carcinoma, as well as cisplatin
      (3 mg/kg, i.p.). These results indicated that kalopanaxsaponin A has potential
      anti-tumor applications.

PMID- 11301856
TI  - Nitric oxide is involved in the immunomodulating activities of acidic
      polysaccharide from Panax ginseng.
AB  - The effects of an acidic polysaccharide isolated from the ethanol-insoluble and
      water-soluble fraction of Panax ginseng C. A. Meyer on immunomodulating
      activities were investigated. A high output nitric oxide synthase (iNOS) was
      shown in female BALB/c mice administered intraperitoneally with the acidic
      polysaccharide from ginseng. Newly synthesized iNOS protein was also observed in
      peritoneal macrophages cultured with interferon-gamma and the acidic
      polysaccharide. Spleen cells from acidic polysaccharide-treated mice did not
      proliferate in response to concanavalin A, but restored the responsiveness by the
      cotreatment of NG-monomethyl-L-arginine (NMMA) with concanavalin A. The treatment
      of mice with aminoguanidine, a specific iNOS inhibitor, alleviated the acidic
      polysaccharide-induced suppression of antibody response to sheep red blood cells.
      Present results suggest that the immunomodulating activities of the acidic
      polysaccharide were mediated by the production of nitric oxide.

PMID- 11301857
TI  - Mutagenicity of natural anthraquinones from Rubia tinctorum in the Drosophila
      wing spot test.
AB  - Mutagenicity of anthraquinone aglycones from Rubia tinctorum L. (Rubiaceae) was
      examined using the somatic mutation and recombination test in Drosophila
      melanogaster. Larvae heterozygous for recessive wing trichome mutations, multiple
      wing hairs (mwh), and flare (flr3) were exposed to test compounds and wings of
      emerged mwh/flr3 females were inspected for the presence of phenotypically mutant
      mosaic spots. No significant increase in the frequency of mutant spots was
      observed after the treatment of Drosophila larvae with pure alizarin,
      xanthopurpurin, and lucidin, or with the crude mixture of anthraquinone
      aglycones. In contrast, the naphthohydroquinone mollugin induced mainly single
      spots that can originate either from somatic mutation or from mitotic
      recombination. Twin spots, consisting of both the mwh and flr3 subclones and
      originating exclusively from mitotic recombination, were also enhanced, but the
      increase was only marginally significant. We suggest that mollugin exhibits both
      the mutagenic and recombinagenic activities.

PMID- 11301858
TI  - Inhibitory effect of baicalein, a flavonoid in Scutellaria Root, on eotaxin
      production by human dermal fibroblasts.
AB  - Eotaxin is an eosinophil-specific chemokine associated with the recruitment of
      eosinophils to sites of allergic inflammation. "Saiboku-to" (Formula magnoliae et
      bupleuri) is a kampo herbal medicine used for the treatment of bronchial asthma
      in Japan. In this study, we investigated the effects of Scutellaria Root, a major
      herb in Saiboku-to and its components such as baicalein and baicalin on eotaxin
      production by IL-4 plus TNF-alpha-stimulated human fibroblasts. An extract of
      Scutellaria Root markedly inhibited eotaxin production. Four major flavonoids
      from Scutellaria Root were found to show inhibitory activity on eotaxin
      production at a concentration of 10 micrograms/ml in the order of baicalein >
      oroxylin A > baicalin > skullcapflavon II. The inhibitory effect of baicalein was
      expressed in a dose-dependent manner, and almost 50% inhibition was observed at
      1.8 micrograms/ml. Furthermore, baicalein prevented human eotaxin mRNA expression
      in IL-4 plus TNF-alpha-stimulated human fibroblasts. These results help explain
      the pharmacological efficacy of Scutellaria Root in the treatment of bronchial
      asthma since it would suppress eotaxin associated recruitment of eosinophils.

PMID- 11301859
TI  - Anticonvulsant properties and bio-guided isolation of palmitone from leaves of
      Annona diversifolia.
AB  - The activity-guided fractionation of the ethanol extract of leaves of Annona
      diversifolia Saff., led to the isolation of palmitone (16-hentriacontanone) as
      the only anticonvulsant active compound. This aliphatic ketone was highly
      effective to diminish pentylenetetrazole (PTZ)-induced clonic-tonic seizures and
      toxicity. Also, it produced a prolongation of the latency for onset of seizures
      and a reduction of the death rate produced by 4-aminopyridine (4-AP) and
      bicuculline (BIC). However, it was inactive to inhibit the kainic acid (KA)- and
      strychnine (STC)-induced seizures. Palmitone did not produce motor incoordination
      and loss of righting reflex which are used as signs of neurological impairment.
      Palmitone (ED50 = 1.85 mg/kg) proved to be a more potent antiepileptic drug
      against the PTZ-induced seizures than etosuximide (ED50 = 59.6 mg/kg), sodium
      valproate (ED50 = 63 mg/kg), and carbamazepine (ED50 > 300 mg/kg) and it was only
      four-fold less potent than diazepam (ED50 = 0.48 mg/kg). The pharmacological
      profile of palmitone suggests that this compound could be acting on the GABAergic
      inhibitory system.

PMID- 11301860
TI  - Neuroprotective effects in gerbils of spiramine T from Spiraea japonica var.
      acuta.
AB  - The neuroprotective effects of spiramine T, an atisine-type diterpenoid alkaloid
      isolated from the Chinese herbal medicine Spiraea japonica var. acuta
      (Rosaceaee), on cerebral ischemia-reperfusion injury produced by 10-min bilateral
      occlusion of the common carotid arteries followed by 5-day reperfusion in gerbils
      were investigated. Intravenous spiramine T (0.38, 0.75, and 1.5 mg.kg-1) markedly
      reduced the stroke index, enhanced the recovery of EEG amplitude during
      reperfusion and decreased the concentrations of cortex calcium and LPO in a dose
      dependent manner. However, no significant effects on water and sodium contents
      were observed. These results suggested that spiramine T exhibited protective
      effects on cerebral ischemia-reperfusion injury in gerbils, and its mechanism
      might be related to reducing calcium accumulation and lipid peroxidation. This is
      the first report on spiramine T as a natural product with neuroprotective
      effects.

PMID- 11301862
TI  - Growth and production of camptothecin by cell suspension cultures of Nothapodytes
      foetida.
AB  - Callus cultures were initiated from stem parts of Nothapodytes foetida on
      Murashige and Skoog's medium supplemented with different growth regulators.
      Suspension cultures were established and the cell biomass was higher in the
      presence of NAA in comparison with 2,4-D. Culture medium supplemented with NAA
      (10.74 microM) and BA (2.22 microM) attained 31.3 g/l DW during 20 days of
      cultivation in shake flasks. In the presence of NAA, maximum concentrations of
      camptothecin (0.035 mg/ml) and 9-methoxycamptothecin (0.026 mg/ml) were found in
      the medium. Alkaloid production was reduced in presence of 2,4-D in the culture
      medium. Cells contained trace amount of alkaloids. Alkaloids were detected and
      identified by means of TLC and HPLC.

PMID- 11301861
TI  - In vitro propagation of Withania somnifera and isolation of withanolides with
      immunosuppressive activity.
AB  - Withania somnifera plantlets were produced in vitro from the shoot-tip of
      aseptically germinated seedlings. Culture conditions were optimized using
      different plant growth regulators which gave rise to 120 shoots from a single
      bud. The plantlets were then transferred to pots and maintained in greenhouse for
      4 months. 90% of these in vitro propagated plantlets survived and showed normal
      growth. Leaves from these plants were used for isolation of the withanolides.
      Methanolic extract of leaves from plantlets growing in tissue culture and those
      transferred to the greenhouse were evaluated for immunomodulatory activity. While
      the extract from greenhouse samples showed potent immunosuppressive activity,
      those from tissue cultures samples did not show any activity. Fractionation and
      characterization of withanolides, using HPLC, NMR, MS methods revealed the
      presence of withaferin A in the greenhouse samples. Our results indicate that
      Withania species may require longer time and better differentiation and also
      natural environment for the production of withaferin A.

PMID- 11301864
TI  - Pheophorbide A from Solanum diflorum interferes with NF-kappa B activation.
AB  - Continuing our search for biogenic NF-kappa B inhibitors we investigated Solanum
      diflorum, used by the Istmo Sierra Zapotec Indians of Mexico in the treatment of
      inflammatory skin conditions. It became obvious very early that the active
      substance seems to be a degradation product of chlorophyll. Pheophorbide A was
      identified as one of the key compounds responsible for the NF-kappa B inhibitory
      activity. The compound interferes with NF-kappa B activation, was cytotoxic if
      exposed to light, but devoid of any cytotoxic activity in the dark.

PMID- 11301863
TI  - A new diterpenoid with antispasmodic activity from Salvia cinnabarina.
AB  - From the leaf surface exudate of the aerial parts of Salvia cinnabarina a new
      secoisopimarane diterpenoid with a non-specific spasmolytic activity on histamine
      , acetylcholine-, and barium chloride-induced contractions in the isolated guinea
      pig ileum was obtained. The IC50 value obtained was comparable with that obtained
      for papaverine. The structure of 3,4-secoisopimara-4(18),7,15-triene-3-oic acid
      was established by 1D and 2D NMR spectroscopic techniques.

PMID- 11301865
TI  - Inhibition of xanthine and monoamine oxidases by stilbenoids from Veratrum
      taliense.
AB  - The bioassay guided refractionation of the methanol extract of roots and rhizomes
      of Veratrum taliense (Liliaceae) yielded five stilbenoids: veraphenol,
      resveratrol, piceid, isorhapontin, and mulberroside E, all inhibiting xanthine
      oxidase (XO, EC 1.2.3.2.) in vitro in a dose-dependent manner with IC50 values of
      11.0, 96.7, 66.1, 70.0, and 78.4 microM, respectively. Veraphenol and
      mulberroside E were found to be mixed XO inhibitors with the Ki and Ki data of
      the former being 32.8 and 239.3 microM, and those of latter 32.5 and 13.8 microM,
      respectively. However, the inhibition on the enzyme by resveratrol, isorhapontin,
      and piceid was shown to be competitive with their Ki values of 9.7, 19.1, and
      14.3 microM, respectively. Among the five stilbenoids, veraphenol and resveratrol
      were also revealed to inhibit competitively monoamine oxidase A (MAO, EC 1.4.3.4)
      with IC50 values at 38.0 and 26.6 microM, and Ki data 36.4 and 47.3 microM,
      respectively. However, none of the stilbenoids was inhibitory on MAO B in our
      assay. The structure-activity relationship examination showed that glycosylation
      of the stilbenoids could reduce the inhibition on XO and diminish the activity
      against MAO A, indicating that the free phenolic hydroxy group of the compounds
      was most likely essential for these bioactivities.

PMID- 11301866
TI  - In vitro anti-Helicobacter pylori activity of irisolidone isolated from the
      flowers and rhizomes of Pueraria thunbergiana.
AB  - The inhibitory effect of isoflavones isolated from the flowers and rhizomes of
      Pueraria thunbergiana (Leguminosae) on the growth of Helicobacter pylori (HP) was
      investigated. Isoflavone glycosides did not inhibit the growth of HP. However,
      their aglycones, irisolidone, tectorigenin and genistein, inhibited HP growth.
      Among them, irisolidone had the most potent inhibitory activity against HP and
      its MIC was 12.5-25 micrograms/ml. Genistein only weakly inhibited the urease of
      HP and H+/K(+)-ATPase of rat stomach: its IC50 were 0.43 and 0.89 mg/ml,
      respectively.

PMID- 11301867
TI  - In vitro activity of a Solanum tuberosum extract against mammary carcinoma cells.
AB  - We investigated the antitumor properties of a Solanum tuberosum extract (STE) on
      F3II mouse mammary carcinoma cells. STE significantly inhibited adhesion on
      fibronectin-coated surfaces and blocked migration of tumor cells in vitro. A
      major gelatinolytic activity (gelatinase) of 82 kD was identified in STE by
      zymographic analysis and characterized by exposure to different experimental
      conditions. Proteolytic activity of STE may be responsible, at least in part, for
      the in vitro effects on mammary carcinoma cells.

PMID- 11301868
TI  - Lignans as anti-tumor-promoter from the seeds of Hernandia ovigera.
AB  - Seven lignans (2-8) isolated from the seeds of Hernandia ovigera L.
      (Hernandiaceae) were tested for their inhibitory effects on Epstein-Barr virus
      early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji
      cells. Using a primary screening test, all the lignans showed inhibitory activity
      with IC50 470-590 mol ratio/32 pmol TPA. The data demonstrated that these lignans
      might be valuable anti-tumor-promoters.

PMID- 11301869
TI  - Essential oils and hexane extracts from leaves and fruits of Cistus
      monspeliensis. Cytotoxic activity of ent-13-epi-manoyl oxide and its isomers.
AB  - Essential oils and hexane extracts from Cistus monspeliensis L. leaves and fruits
      were analysed by GC-MS. Manoyl oxide and its isomers, 3 beta-hydroxy-manoyl
      oxide, 3 beta-hydroxy-13-epi-manoyl oxide, as well as 3 beta-acetoxy-13-epi
      manoyl oxide were detected for the first time in C. monspeliensis L. Ent-13
      epimanoyl oxide was isolated from the hexane extract of leaves and its structure
      was determined using spectroscopic methods. In vitro cytotoxic activity of ent-13
      epi-manoyl oxide and mixtures of manoyl oxide isomers at 10(-4) M concentrations
      ranged from 11.1 to 32.2% of the activity for a vinblastine control evaluated
      against nine leukemic cell lines. The results showed that the manoyl oxide isomer
      mixtures as well as ent-13-epi-manoyl oxide exhibited a slight growth inhibiting
      activity.

PMID- 11301870
TI  - Cnidicin, a coumarin, from the root of Angelica koreana, inhibits the
      degranulation of mast cell and the NO generation in RAW 264.7 cells.
AB  - Cnidicin (1) and five related coumarins were isolated from the root extract of
      Angelica koreana (Umbelliferae) as active principles responsible for the
      inhibitory effect on the degranulation process of cultured mast cells. Cnidicin
      (1) demonstrated a significant inhibition upon the release of beta-hexosaminidase
      from the cultured RBL-2H3 cells in a dose dependent manner (IC50 value, 25
      microM) and upon the nitric oxide production from the activated RAW264.7 cells
      (IC50 value, 7.5 microM). In agreement with this, cnidicin inhibited the
      expression of nitric oxide synthase in RAW264.7 cells.

PMID- 11301871
TI  - Local anaesthetic activity of (+)- and (-)-menthol.
AB  - In this work we studied the local anaesthetic activity of (+)- and (-)-menthol, a
      substance used after topical application to induce a feeling of coolness. We
      compared its activity to two chemically related compounds thymol and (-)
      menthone. Anaesthetic activity was evaluated in vivo in the rabbit conjunctival
      reflex test and in vitro in a rat phrenic nerve hemidiaphragm preparation. Both
      enatiomers of menthol (10(-4)-1 micrograms/ml), but not thymol and (-)-menthone,
      were able to drastically reduce, in a dose-dependent manner, the electrically
      evoked contractions of rat phrenic hemidiaphragm. In the rabbit conjunctival
      reflex test, treatment with a solution of (+)- and (-)-menthol (30-100
      micrograms/ml) allowed a dose-dependent increase in the number of stimuli
      necessary to provoke the reflex, thus confirming in vivo the local anaesthetic
      activity observed in vitro. Similar to the in vitro results, thymol and (-)
      menthone were ineffective also in the in vivo test. In conclusion, these data
      evidence the local anaesthetic activity of menthol, which appears to be strictly
      dependent on its chemical structure.

PMID- 11301872
TI  - Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice.
AB  - Piperine (1), an alkaloid of black and long peppers, inhibited gastric emptying
      (GE) of solids/liquids in rats and gastrointestinal transit (GT) in mice in a
      dose and time dependent manner. Compound 1 significantly inhibited GE of solids
      and GT at the doses extrapolated from humans (1 mg/kg and 1.3 mg/kg p.o. in rats
      and mice, respectively). However, at the same dose the effect was insignificant
      for GE of liquids. One week oral treatment of 1 mg/kg and 1.3 mg/kg in rats and
      mice, respectively, did not produce a significant change in activity as compared
      to single dose administration. GE inhibitory activity of 1 is independent of
      gastric acid and pepsin secretion.

PMID- 11301873
TI  - Modulatory effect of aliphatic acid amides from Zanthoxylum piperitum on isolated
      gastrointestinal tract.
AB  - beta-Sanshool and gamma-sanshool, unsaturated aliphatic acid amides isolated from
      the pericarpium of Zanthoxylum piperitum De Candolle (Rutaceae), relax the
      circular muscle of the gastric body, as well as contract the longitudinal muscle
      of the ileum and distal colon in an experimental system using the
      gastrointestinal tract isolated from a guinea pig.

PMID- 11301874
TI  - In vitro plantlet regeneration in Panax sikkimensis.
AB  - A three-step procedure for complete plantlet regeneration via somatic
      embryogenesis has been developed in Panax sikkimensis. Somatic embryos (SE) were
      induced in root callus upon lowering the level of 2,4-D from 1.0 mg/l to 0.25
      mg/l in the callusing medium. Maturation of SE occurred on a half-strength MS
      medium with 0.5 mg/l each of BAP and GA3. An exposure for 15 days of cotyledonary
      and heart-shaped SE to 1.0 mg/l IBA in liquid shake 1/2 MS medium significantly
      improved the rate of embryo-to-plantlet conversion and plantlet quality. The
      procedure has now allowed the retention of high regeneration potential of the
      root callus for over three years.

PMID- 11301875
TI  - Authentic identification of stigma Croci (stigma of Crocus sativus) from its
      adulterants by molecular genetic analysis.
AB  - Stigma Croci, stigma of Crocus sativus L., is a precious traditional Chinese
      medicine, which is commonly used to activate blood circulation and to dissipate
      blood stasis. Three plant species, Carthamus tinctorius L., Hemerocallis fulva
      (L.) L. and Hemerocallis citrina Baroni, could carry the name Stigma Croci in the
      commercial markets of South East Asia. However, C. sativus is the only one that
      has proven its effectiveness, while the others could act as adulterants. The
      authentic identification of C. sativus on the market is difficult. By using
      molecular genetic method, the spacer domains of 5S-rRNA were cloned from the
      genomic DNAs that were isolated from C. sativus, C. tinctorius, H. fulva and H.
      citrina. The cDNAs encoding the spacer domains, about 300 to 500 bp, were
      sequenced. The nucleotide sequences of these four species showed great diversity,
      which could serve as markers for authentic identification of Stigma Croci to
      distinguish from its substitution and counterfeit.

PMID- 11301876
TI  - Dihydrochalcones from Piper longicaudatum.
AB  - Bioactivity-guided fractionation of an ethanolic extract of the leaves and twigs
      of Piper longicaudatum Trelease & Yunker (Piperaceae) resulted in the isolation
      of one new (1) and three known (2-4) dihydrochalcones. The known compounds are:
      2',6'-dihydroxy-4'-methoxydihydrochalcone (2), 2',6',4-trihydroxy-4'
      methoxydihydrochalcone (asebogenin) (3), and 2'-hydroxy-4'-methoxy-2'-[1-hydroxy
      1-methylethyl]-2",3"-dihy- drofurano[4",5":5',6"]-3"-[2-hydroxy-5
      methoxycarbonylphe- nyl]dihydrochalcone (piperaduncin B) (4). The new compound is
      2'-hydroxy-4'-methoxy-2"-[2-hydroxy-5-methoxycarbonyl- phenyl]
      furano[4",5":5',6']-dihydrochalcone (longicaudatin) (1). Compounds 1-4 were
      tested for antibacterial activity against S. aureus and methicillin-resistant S.
      aureus (MRSA); only compound 3 showed inhibitory activity (IC50 of 10 and 4.5
      micrograms/ml, respectively).

PMID- 11301877
TI  - Isoquinoline alkaloids from Thalictrum delavayi.
AB  - Two new protoberberine alkaloids, 2,3,9,10-dimethylenedioxy-8-oxoprotoberberine
      (1) and 2,3,9,10-dimethylenedioxy-1,8-dihydroxyprotoberberine (2), together with
      nine known isoquinoline-type alkaloids were isolated from the roots of Thalictrum
      delavayi. Their structures were elucidated by spectral methods. Among these
      compounds, pseudoprotopine showed competitive inhibition activity by DA receptor
      binding assay (D1) in vitro. The competitive inhibitions were 87.5% (10(-4) M)
      and 15.6% (10(-6) M), respectively.

PMID- 11301878
TI  - Crinane and lycorane type alkaloids from Zephyranthes citrina.
AB  - Eight alkaloids have been isolated from Zephyranthes citrina (Amaryllidaceae).
      The alkaloid oxomaritidine is reported here for the first time from a natural
      source. The structure and stereochemistry of the alkaloids were determined by
      physical and spectroscopic methods.

PMID- 11301879
TI  - Acutudaurin from cultured roots of Menispermum dauricum.
AB  - A new alkaloid, acutudaurin, was isolated from cultured roots of Menispermum
      dauricum, a rich source of the chlorine-containing alkaloid acutumine and its
      dechlorinated analogue dechloroacutumine. The structure of acutudaurin was
      determined to be 2',3'-dihydro-5-hydroxy-4,6',7'-trimethoxy- 1'-methylspiro[3
      cyclohexene-1,10'-[3a,7a]propano[1H]indole]-2,5'(4'H)-dione by spectroscopic
      methods.

PMID- 11301880
TI  - Steroidal saponins from Tribulus terrestris.
AB  - Three new steroidal saponins were isolated from the fruits of Tribulus
      terrestris, and their structures were elucidated as (25R,S)-5 alpha-spirostane-12
      one-3 beta-ol-3-O-beta-xylopyranosyl(1-->2)- [beta-xylopyranosyl(1-->3)]-beta
      glucopyranosyl(1-->4)-[alpha-rhamno- pyranosyl(1-->2)]-beta-galactopyranoside; 26
      O-beta-glucopyranosyl-(25S)-5 alpha-furostane-12-one-3 beta,22 alpha,26-triol-3-O
      beta-glucopyranosyl(1-->2)-beta-galactopyranoside; 26-O-beta-glucopyranosyl-(25S)
      5 alpha-furostane-12-one-3 beta,22 alpha,26-triol-3-O-beta-glucopyranosyl(1-->4)
      [alpha- rhamnopyranosyl(1-->2)]-beta-galactopyranoside, respectively, by
      spectroscopic analysis and color reaction.

PMID- 11301881
TI  - [Anatomy of the shoulder joint].
AB  - The shoulder joint and its associated joints form one of the most complex joint
      systems of the human locomotor apparatus. Its large range of motion is made
      possible by the interplay of 5 joints: sternoclavicular-joint, acromioclavicular
      joint, glenohumeral joint, thoracoscapular joint and subacromial joint. The
      rotator cuff works mostly as an active stabilizer of the shoulder joint. The
      supraspinatus muscle causes a compression of the humerus in the glenoid mainly,
      furthermore it effects synergistic the abduction with the delta muscle. On the
      basis of its lever-arm the supraspinatus works between 0 and 60 degrees abduction
      the most optimally. With failure of the supraspinatus, the deltoideus can almost
      completely take its function. The inferior glenohumeral ligament-complex is the
      main passive stabilizer. The blood supply of the humerus head is ensured mainly
      by the a. circumflexa anterior and its rami ascendents, by several small branches
      from the a. circumflexa posterior and over intraosseous anastomoses. The most
      important vessel of the cap is the intraosseous a. arcuata out of the ramus
      ascendens lateralis of the a. circumflexa anterior.

PMID- 11301882
TI  - [Rotator cuff rupture].
AB  - Rotator cuff tears can result separately or from any combination of vascular,
      degenerative, mechanical, or traumatic causes. A correct diagnosis is sometimes
      difficult since the clinical findings and symptoms vary largely. Treatment
      requires an early surgical intervention either with a suture of the tear or a
      reconstruction in case of larger tears or defects depending on the tear size,
      since early surgical treatment leads to better results. With surgery also it is
      more likely to prevent cuff arthropathy with subsequent joint destruction and
      painful loss of function.

PMID- 11301883
TI  - [Chronic instability and fixed dislocation of the shoulder].
AB  - Chronic instabilities may be traumatic or atraumatic, unidirectional or
      multidirectional. It is important to distinguish between symptomatic instability
      and asymptomatic hyperlaxity. Posttraumatic, unidirectional anterior instability
      without hyperlaxity is the most common form of instability. The patient presents
      apprehension, the sulcus-sign is negative. Posttraumatic, unidirectional
      instability with hyperlaxity is due to an adequate trauma, both the apprehension
      test and the sulcus sign are positive. The treatment of traumatic instability is
      surgically with respect to the underlying pathology of the ligaments, labrum and
      capsule. The "golden standard" is the reconstruction of the capsulolabral
      complex. The repetitive microtraumatic instability is seen in overhead athletes
      with elongation or disruption of the capsule. The typical patient presents with
      painful subluxations, the instability may be unidirectional or multidirectional.
      The treatment is conservatively. Multidirectional instability with hyperlaxity is
      defined as symptomatic instability in at least two directions of instability with
      multidimensional hyperlaxity. These individuals will also report on pain rather
      than instability. The apprehension test is positive in at least two directions,
      the sulcus sign is positive as well. The patients are responsive to an intensive
      rehabilitation program for 6-12 months. Open capsular shift or thermal capsular
      shrinkage may be successful after failed conservative treatment. Multidirectional
      instability without hyperlaxity is extremely rare and is due to more than one
      adequate trauma with traumatic instability in different directions. The
      apprehension test is positive, the sulcus sign negative. The treatment is
      surgically. The fixed dislocation is posterior in most of the cases and
      frequently being missed primarily. It is seen in unconscious, multiple-injured
      patients or after grand mal or electroshock seizures. The reduction may be either
      closed or open depending on the interval between trauma and diagnosis. Voluntary
      instability represents a subset of individuals with atraumatic instability. The
      patients can dislocate and reduce their shoulder, have no pain and do not develop
      arthritis. They do not require a special therapy.

PMID- 11301884
TI  - [Current treatment concepts in first-time dislocation of the shoulder joint].
AB  - The rapid development of arthroscopic techniques has raised questions on the
      treatment of first shoulder dislocations. Primary arthroscopic or even open
      labral repair have been recommended. However, the available prospective studies
      demonstrate a recurrence rate of not more than 50% in the global population. This
      number increases steeply if certain risk factors are present: young age (under 25
      years), shoulder sports, adequate trauma with acute unidirectional instability.
      For this selected group, arthroscopic labral repair should be proposed and should
      be performed by a surgeon specifically trained in this advanced arthroscopic
      technique. Repair of the labrum is feasible with various arthroscopic techniques,
      whereas the shortening of redundant capsular areas still poses problems. The
      efficiency of laser- or heat-shrinking of the shoulder capsule must yet be
      proven.

PMID- 11301885
TI  - [Recurrent luxations after arthroscopic refixation of the labrum using suture
      anchors in traumatic ventral shoulder luxation].
AB  - OBJECTIVE: Recurrence rates after arthroscopic labral reconstruction for anterior
      shoulder instability are still higher than after open procedures. Therefore,
      proper selection of patients becomes increasingly important. The aim of this
      study was to investigate factors influencing recurrence rates after arthroscopic
      labral repair with suture anchors. PATIENTS AND METHODS: We examined 53 patients
      (43 male, 10 female) with traumatic anterior shoulder dislocations, who were
      treated with arthroscopic labral repair using Fastak-Suture anchors between 1995
      and 1996. The average follow-up time was 18 (12-30) months. The mean age of the
      patients at the time of operation was 27 (15-44) years. RESULTS: Postoperatively,
      11 patients (20.7%) reported on redislocations. Recurrence rates increased
      significantly in patients with more than 4 preoperative dislocations and in
      patients with bony Bankart lesions. In patients without redislocations, the mean
      Rowe score improved from 65.9 (SD +/- 12.3) preoperatively to 88.6 (SD +/- 12.5)
      at follow-up. Thus, there were 24 excellent, 9 good and 6 fair results, while in
      3 patients with persisting signs of shoulder instability results had to be
      estimated as poor. Deficits in the range of motion of more than 15 degrees were
      seen in 7 patients with predominant affection of the external rotation.
      CONCLUSION: Frequent preoperative dislocations and bony Bankart lesions
      contribute substantially to high recurrence rates after arthroscopic labral
      repair. Therefore, in these cases open procedures should be preferred.

PMID- 11301886
TI  - [Conservative treatment of dislocated proximal humeral fractures].
AB  - Between 11/1989 and 6/1998 52 patients (10 m., 42 f., age median 72 years, 31-88)
      with proximal humeral fractures have been treated by conservative means
      (angulation of humeral head > 45 degrees and/or shaft displacement > 1 cm and
      displacement of greater tuberosity > 0.5 cm). In 37 patients (71%, 31 f., 6 m.,
      age median 75 years, 36-88) a clinical and radiological follow-up could be
      obtained after median 20 months (3-93). According to the Neer-classification,
      subcapital 2-part fractures were found in 19 cases and 3-part fractures in 12
      cases. 4-part fractures were diagnosed in 6 cases. By using the Constant-Score,
      the final result was scored "excellent" in 10 patients and "good" in 13 patients.
      In 7 patients each the results achieved were "moderate" or "poor". The underlying
      cause for the poor results was primarily due to persisting painful impairment in
      range of motion and loss of strength. Radiologically, persisting axial deviation
      was present in 23 cases, arthrosis in 14 patients and humeral head necrosis in 8
      patients. Most commonly, poor functional and radiological results occurred in 4
      part fractures. However, conservative therapy of displaced 2-part and 3-part
      fractures is a considerable therapeutical option since the final results are
      predominantly good. In contrast, due to the poor results after conservative
      therapy 4-part fractures should be treated surgically.

PMID- 11301887
TI  - [Surgical treatment of proximal humeral fractures. Is the T-plate still adequate
      osteosynthesis procedure?].
AB  - No general agreement exists on the operative therapy of displaced proximal
      humeral fractures. The purpose of this study is to evaluate different internal
      fixation techniques (plate fixation, figure-of-eight tension wiring, lagscrew)
      and to verify if the plate fixation is still an adequate therapy in the treatment
      of displaced proximal humeral fractures. A follow-up investigation was conducted
      in 51 patients after an average of 4.2 years. A T-plate fixation was performed in
      62.7%, a minimal invasive technique in 21.6% and a shoulder prosthesis in 15.7%
      of these patients. At follow-up 60.7% of the patients with a 3- or 4-part
      fracture had good or excellent results in the Constant score (59% T-plate, 66%
      minimal invasive). Humeral head necrosis was seen in 15.9% of the patients with a
      T-plate fixation and in 9.1% of the patients with minimal invasive techniques.
      Based on our results and the reviewed literature we can confirm advantages of the
      minimal invasive techniques in the treatment of 4-part fractures. However, good
      results can be obtained with T-plate fixation in 2- or 3-part fractures
      especially in younger patients.

PMID- 11301888
TI  - [Chances in surgical treatment of bronchial carcinoma under palliative
      conditions].
AB  - Palliative surgery aims at symptomatic relief in patients in whom curative
      therapy seems not feasible. When diagnostic imaging techniques describe advanced
      stage IIIa, IIIb or IV malignancy, despite of palliative intention curative
      resection may still be possible. Objective of the present study was to
      investigate lung cancer patients undergoing surgery with palliative intent and to
      compare their prognosis with patients whose tumor resection had been complete
      (R0) or incomplete (R1/R2). PATIENTS AND METHOD: Patients were assigned to one of
      the three groups on the basis of the following criteria: palliative intention
      with subsequent complete resection (group I, n = 11); curative intention with
      subsequent incomplete resection (group II, n = 38), palliative intention with
      incomplete resection (group III, n = 23). Additionally 3 patients were operated
      on by explorative thoracotomy. A total number of 75 patients was therefore
      investigated. Median follow-up period was 34.5 months. Survival rates were
      calculated using the Kaplan-Meier method. RESULTS: The following procedures
      involving resection of pulmonary tissue were performed: pneumonectomy (n = 10),
      extended pneumonectomy (n = 32), lobectomy (n = 5), extended lobectomy (n = 11),
      sleeve lobectomy (n = 7), bilobectomy (n = 3), extended bilobectomy (n = 4). The
      30 days hospital mortality rate was 13%. Median survival times were 25.5 months
      in group I, 12.8 months in group II and 7.7 months in group III (statistical
      significance: group I vs. group II/III, p < 0.05). CONCLUSIONS: Results of the
      present study show that patients with bronchial carcinoma in advanced tumor
      stages III and IV may still benefit from pulmonary resection, particularly when
      reduction of their somatic complaints is considered. In 11 patients, R0 resection
      was feasible leading to a statistically significant prolongation of their
      survival rates.

PMID- 11301889
TI  - [Surgical treatment of malignant thoracic schwannomas].
AB  - The objective of this study is to evaluate the results after surgical treatment
      of malignant tumors arising from the peripheral nerves of the thorax under
      consideration of adjuvant therapy modalities. PATIENTS AND METHODS: Between 1988
      and 1998, 9 patients (6 males, 3 females) underwent surgical treatment for MTNSO
      and 35 pts. for benign neurogenic tumors. The mean age in patients with malignant
      tumors was 45 years (range, 25 to 73 years). 3 pts. with MTNSO (33.3%) had
      neurofibromatosis (von Recklinghausen's syndrome) compared to 8.6% (3/35) in
      patients with benign neurogenic tumors. RESULTS: In patients with MTNSO partial
      chest wall resections (n = 4) including sternectomy (n = 1), lung resections (n =
      2), paravertebral (n = 1) and mediastinal tumor resection (n = 1) and palliative
      resection of pleural recurrence (n = 1) were performed. Radical resection was
      achieved in 5 pts. (55.5%). There was no postoperative mortality. 3 patients
      (33.3%) had postoperative complications: wound infection (n = 2) and wound
      dehiscence due to fall with consequent pleural infection (n = 1). Adjuvant
      therapy was performed in two pts. (adjuvant radiotherapy/chemotherapy for
      metastatic disease n = 1; adjuvant chemotherapy/adjuvant radiotherapy after
      resection of recurrent tumor n = 1). Early recurrence is documented in 2 pts.
      (after 3 and 6 months). Two pts. are alive and free of disease at three years,
      and the patient after sternectomy with recurrent disease at 20 months. Three pts.
      died 8, 9 and 26 months after the primary surgical procedure. The first
      postoperative examination (at three months) in the remaining patient showed no
      evidence for recurrent disease. CONCLUSION: Patients with MTNSO have an
      unfavourable prognosis and local recurrence is frequent even after radical
      surgical therapy. Therefore an adjuvant treatment in these patients may be
      justified, even if the value of these therapy modalities is not proved yet. A
      tumor-free long-term survival especially after complete surgical resection is
      possible in selected cases.

PMID- 11301890
TI  - [Asbestos-induced malignant mesothelioma of the tunica vaginalis testis].
AB  - Since 1977 the diffuse malignant mesothelioma of the pleura and peritoneum caused
      by asbestos represents one of the most often compensated occupational cancers in
      Germany. Because of the probability of an asbestos-related etiology, it is
      considered as a "signal tumour", mainly indicating exposure to asbestos dust at
      the workplace. Two cases of histologically confirmed rare malignant mesothelioma
      of the tunica vaginalis testis are presented. Previous exposure to asbestos at
      the workplace is to be considered as a causal factor in both tumors. If cases of
      mesothelioma occur the criteria for indicating an occupational disease (No. 4105
      of the German Law of Occupational Diseases, BKV) are fulfilled.

PMID- 11301891
TI  - [Osteochondral shear fractures in children. A case report and critical review of
      the literature].
AB  - Only few articles on osteochondral flake fractures in children have been
      published. Diagnostic tools have been improved over the past decades, but still,
      diagnosis of severe osteochondral defects may be delayed. The presented case
      report describes the different techniques currently being available for the
      diagnosis of osteochondral flake fractures. The different therapeutic options for
      the treatment of osteochondral flake fractures in children are discussed based on
      the current literature. This article demonstrates the necessity to consider
      severe injuries, even if impressive clinical symptoms are lacking.

PMID- 11301892
TI  - [Fritz Konig (1866-1952): pioneer of osteosynthesis and his influence on
      traumatology].
AB  - Fritz Konig (1866-1952) was 1918-1935 ordinary professor of surgery at the
      University of Wuerzburg. A main interest of his work was the technique and
      indication of osteosynthesis. Since 1900 he investigated methods (wire suture,
      intra- and extramedullary splint, external fixator, plate) and materials (ivory,
      steel; wire, screws). All his life he aimed to standardize the technique of
      osteosynthesis, to work out and spread clear indications for the surgical
      treatment of fractures, and to carry his point against the resistance of the
      social accident insurance caused by bad results of a lot of surgeons. His
      importance is not based on the invention of a great deal of instruments but on
      his endeavour for the fundamentals of osteosynthesis.

PMID- 11301893
TI  - [Hand port-assisted laparoscopic surgery].
AB  - The dramatic benefits of laparoscopic cholecystectomy or appendectomy for
      patients encouraged surgeons to use minimal access operative technique in the
      treatment of other more complex surgical procedures [2, 3]. The authors report on
      their experiences with 14 patients operated by hand-port assisted laparoscopic
      technique for benign colorectal diseases. The mortality rate was zero. The
      operation times compared to the laparoscopically operated previous 14 patients
      with equal diagnosis did not differ significantly (hand-port: 124-186 min; lap.:
      121-176 min). The begin of bowel movements and the postoperative hospital stay
      were comparable to those of laparoscopic surgery. There were no major
      complications. No conversion to an open procedure was necessary. As the hand-port
      device allows the surgeon to insert his (usually non-dominant) hand into the
      abdominal cavity during the procedure, the hand-port device seems to combine the
      laparoscopic benefits with the advantages of a conventional open approach (manual
      exploration, blunt dissection, control of hemostasis) without loss of
      pneumoperitoneum [10]. Even though hand-assisted operations have not gained
      widespread acceptance, they recently demonstrated their value especially in more
      complex laparoscopic procedures like splenic and gastric resections, nephrectomy
      and colorectal surgery [6, 10, 18, 21, 23-24]. The regaining of tactile sensation
      which is an essential surgical tool may encourage less experienced colleagues to
      perform more complex operations. The authors suggest that the hand-port device
      could be a useful tool in the armentarium for colorectal surgery. Further
      randomized trials are needed to evaluate the benefits of this technique.

PMID- 11301894
TI  - [2 rare cases of resuscitation].

PMID- 11301895
TI  - [Transplantation surgery. II].

PMID- 11301896
TI  - Physician credentialing.

PMID- 11301897
TI  - Healthcare managers at work: women and men of healthcare, be careful out there!

PMID- 11301898
TI  - Acute care hospitals and community health.
AB  - Hospital boards and executives must resist the pressure to become all things
      health in the community. Hospital executives must educate their boards about the
      importance of concentrating on their core business and avoiding entangling and
      potentially risky ventures in peripheral and unrelated activities. They can and
      should participate in community health initiatives, but such efforts should, at
      most, be incidental to delivery of acute care services. The Drucker quote at the
      beginning of this column should be a warning to all who would venture even a
      short distance from their core business.

PMID- 11301899
TI  - Justice and managed care: an oxymoronic notion?

PMID- 11301900
TI  - How to improve patient education.
AB  - There are a variety of ways to improve patient education. Healthcare managers
      should investigate the best practices used by the most successful providers and
      adapt the best ideas for use in their own organizations. Healthcare providers are
      increasingly recognizing that developing an effective system of patient education
      is one of the most cost-effective ways to maintain the health status of
      chronically ill patients. In an era of capitated payment and competition, the
      provider who can successfully partner with its patients to manage their health
      will be the one to survive.

PMID- 11301901
TI  - National healthcare spending and fiscal control: comparisons among 15 countries.

PMID- 11301902
TI  - [Pathologic evaluation of orthotopic liver transplantation in Hungary].
AB  - A total of 81 orthotopic liver transplantations were performed on 74 patients
      between January 1995 and December 1999 at the Department of Transplantation and
      Surgery of the Semmelweis University in Budapest. Indication for transplantation
      was liver cirrhosis in 57 cases, 10 patients were transplanted due to fulminant
      liver failure, while 7 patients underwent transplantation because of liver
      metastasis of different semimalignant tumours. During the above period,
      retrospective studies on 205 pre- and posttransplantation liver biopsies, 74
      explanted livers, 7 explanted liver grafts and 22 autopsy cases were performed at
      the First Institute of Pathology and Experimental Cancer Research of the
      Semmelweis University in Budapest. A number of 116 protocol biopsies (dates as
      zero time, 7th day, 6th month and 12th month) and 73 non-protocol biopsies (taken
      due to liver allograft dysfunction) were analysed. Different gradings of acute
      rejection--characterised by trias of portal inflammation, venous endothelitis and
      bile duct damage--were detected in 62 cases. Chronic rejection occurred in 7
      patients, with 4 cases of vanishing bile duct syndrome and one of the case of
      foam cell arteriopathy, add to 2 cases of chronic rejection characterized by
      undetermined bile duct damage. The present study includes the evaluation of 22
      autopsy cases according to liver transplantation in Hungary, with the finding
      that liver allograft insufficiency was the main cause of mortality. Authors
      conclude that pathomorphological analysis has an important role in relation to
      liver transplantation.

PMID- 11301903
TI  - [The effect of a single-dose intravenous vinpocetine on brain metabolism in
      patients with ischemic stroke].
AB  - The effect of a single-dose i.v. infusion of vinpocetine on the cerebral blood
      flow (CBF) and glucose metabolism of post-stroke patients was studied by
      measuring the regional and global cerebral metabolic rates of glucose (CMRglu)
      and the corresponding kinetic constants before and after treatment. Transcranial
      Doppler (TCD) and single photon emission tomography (SPECT) measurements were
      also performed. The cerebral glucose metabolism was significantly higher in the
      contralateral hemisphere than in the affected one before therapy. In the affected
      hemisphere the regional glucose metabolism was inhomogenous: relatively low
      values were measured in the stroke region, whereas it was increased in the
      peristroke region. Although a single-dose vinpocetine treatment did not affect
      significantly the regional or global metabolic rates of glucose, the glucose
      transport (both intracellular up-take and release) was strongly affected in the
      whole brain, in the contralateral hemisphere and in the peri-infarct area of the
      symptomatic hemisphere. A slightly increased (not significant, N. S.) cerebral
      blood flow could be observed in the contralateral and a decreased flow (N. S.) in
      the symptomatic hemisphere.

PMID- 11301904
TI  - [Cholesterol granuloma at the sella region: a new method of the differential
      diagnosis of craniopharyngioma].
AB  - Cholesterol-granuloma is a pseudotumoral mass that is believed to enlarge by a
      self-perpetuating sequence of repeated hemorrhages and reparative tissue
      reaction. Albeit an almost ubiquitous phenomenon throughout the body, cholesterol
      granuloma has recently been appreciated as a distinctive lesion mimicking or
      associated with craniopharyngiomas. Upon review of a surgical series of 15
      purported craniopharyngiomas, the authors identified 3 such occurrences. All were
      characterized by a predominance of slit-like cholesterol clefts with multi
      nucleated giant cells embedded in a fibrotic stroma permeated with lipid laden
      macrophages, lymphocytes, as well as organizing hemorrhage. Non-craniopharyngioma
      specific cuboidal epithelium was present in one case. The mean age of patients-
      all males--with cholesterol-granuloma was 26 years, and all but one had an
      intrasellar tumor component. Clinical symptoms referrable to hypopituitarism
      predominated. At variance with the above, patients with adamantinomatous or
      papillary craniopharyngiomas were 23.5 and 46 years old, respectively, and
      presented with neurological deficits or ones due to hypothalamic involvement by
      their tumors. With marginal central nervous tissue present in 53 percent of the
      specimens, 75 percent of adamantinomatous craniopharyngiomas, but only 12 percent
      of cholesterol-granulomas showed invasive growth. At present cholesterol
      granulomas are conceived as a clinicopathologically distinctive lesion of
      uncertain origin. They most probably represent a clinically relevant entity in
      the ontogenesis of adamantinomatous craniopharyngiomas with predisposing factors
      yet to be elucidated.

PMID- 11301905
TI  - [Outbreak of human calicivirus infection in a hospital department].
AB  - Human caliciviruses (HuCV)--such as Norwalk-like and Sapporo-like viruses-
      members of the family Caliciviridae, are a major cause of acute non-bacterial
      gastroenteritis in persons of all ages worldwide. They are important pathogens in
      food- and waterborne diseases in which the transmission can often be traced to
      fecally contaminated water or foods, and spread by person-to-person contact,
      vomitus or airborne droplets. HuCV-associated outbreaks involving large numbers
      of people usually occur in settings where people congregate. Between May 9 and
      24, 2000, an outbreak of acute, mild, nonbacterial gastroenteritis occurred in
      woman, chronic psychiatric ward of a county hospital where 35 of 143 persons
      (24.5%) were registered with characteristic symptoms. Reverse transcription
      polymerase chain reaction (RT-PCR) assay was used for virus detection. HuCV was
      found in stool samples in 12 of 17 (70.6%) ill persons. This is the first HuCV
      associated hospital outbreak of gastroenteritis in Hungary where HuCV was
      successfully detected by molecular method and its etiologic role was also
      supported by epidemiologic investigation.

PMID- 11301906
TI  - [Increased sensitivity to balsams and fragrances among our patients].
AB  - Allergic contact dermatitis caused by fragrances and balsams play an increasingly
      important role in the daily practice of dermatology. Based on county tests, the
      authors have found high increase in 1999, which is in accordance with
      observations made abroad and the prognosis of earlier tests. The balsam of Peru
      and the fragrance mix are among the leader allergens, and this should be
      considered during treatment. Irrespective of age, scentless and hypoallergen
      cosmetics are to be used.

PMID- 11301907
TI  - [National model for the education of family physicians in the county Gyor-Moson
      Sopron].

PMID- 11301908
TI  - [Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor
      antagonists. Pharmacologic features].
AB  - The development of pharmacological agents that block the renin-angiotensin system
      (RAS) specifically have helped to define all the components of the system and
      their contribution to blood-pressure control and to the pathogenesis of
      hypertension, congestive heart failure and chronic renal failure. The angiotensin
      converting-enzyme inhibitors (ACEi) are among all available drugs that interfere
      with the RAS, the most efficient, so far, in the treatment of several
      cardiovascular diseases, with comfortable posologic schemes and an acceptable
      safety profile. The most important difference between them are more related to
      pharmacokinetic profile rather than to pharmacodynamic characteristics. With the
      use of ACEi the interference with other neurohumoral systems is unavoidable and
      the controversy has been pharmacologically and clinically installed. With the
      advent of oral selective AT1 angiotensin II receptor blockers (ARB) the
      pharmacological interference became eventually much more selective. Their
      antihypertensive efficacy is identical and their tolerability is better than that
      showed by ACEi. The ARBs differ mainly in their pharmacokinetics and in their
      binding capacity to the AT1 angiotensin receptor. The results of several ongoing
      clinical trials will show if the ARBs as ACEi will be capable to protect target
      organs and to promote a significant reduction in cardiovascular morbility and
      mortality. In parallel there is an intense experimental and clinical research
      with other groups of drugs which also markedly interfere with RAS: renin
      inhibitors, chymase inhibitors and simultaneous inhibitors of vasopeptidases
      (ACE, endothelin converting-enzyme, neutral endopeptidase). From the
      pharmacological point of view, it is now possible to block effectively RAS with
      some relevant clinical results that will be certainly widen in the near future.

PMID- 11301909
TI  - [Converting enzyme inhibitors in the diagnosis of secondary arterial hypertension
      --focus on the captopril test].
AB  - The first application of angiotensin converting enzyme (ACE) inhibitors it was
      the treatment of arterial hypertension. Latter news application appears such as:
      heart failure, myocardial infarct, nephropathy and diabetic proteinuria.
      Captopril, the first oral ACE inhibitor was used, since 1986, in the diagnostic
      screening of renovascular hypertension (RVH). Since then other authors recognised
      the importance of captopril test in the detection of RVH, advising also it's
      application in the diagnosis of primary aldosteronism and pheocromocithoma. Based
      in different publications the sensitivity of captopril test is 40%-100% and the
      specificity 72%-100%. There are several reasons to explain the differences
      between these results. In our opinion, these observations appeared as a
      consequence of the different methodology used. Despite the fact that alternative
      procedures to captopril test in the screening of RVII do exist this is, in our
      opinion, the most simple, cheap, safe and efficient test available at the moment.

PMID- 11301910
TI  - [ACE inhibitors versus AR II antagonists. Their role in arterial hypertension].
AB  - The A II antagonists (RA II antagonists) are a new group of anti-hypertensive
      drugs with five years of clinical use. They were investigated after the knowledge
      of independent ways to get angiotensin II. They block AT1 receptor. It's possible
      that, after AT1 block, the high plasmatic levels of AII stimulate the AT2
      receptors with vasodilation and anti-proliferative activity. We are waiting for
      the results of several big prospective studies with RA II antagonists on
      cardiovascular morbidity and mortality. At present time, the first indication for
      its use is the appearance of cough when taking ACE inhibitors. The association of
      ACE inhibitors and RA II antagonists can improve some clinical conditions like
      dilated hypertensive cardiopathy, nephropathy or refractory hypertension.

PMID- 11301911
TI  - [Angiotensin converting enzyme inhibitors in the treatment of heart failure].
AB  - A brief revision of the clinical trials that support the use of ACE inhibitors in
      patients with heart failure is made in this paper. The use of ACE inhibitors in
      clinical practice, recommendations for it's use in specific population and
      perspectives of ACE inhibitors use in the future of heart failure are discussed.

PMID- 11301912
TI  - [Heart failure: neurohumoral approach to treatment].
AB  - Heart failure is a frequent human disease, partly related to anomalous activation
      of the defense systems, following a cardiovascular aggression. Increases in the
      prevalence of heart failure have been observed in the so-called occidental
      culture countries, probably due to the increased prevalence of cardiovascular
      risk factors, ageing population, and heart failure patients' survival. During the
      last two decades, intensive investigation in the human and non-human set have
      contributed to better knowledge of the patophysiology, the prevention and the
      therapeutic approach of heart failure. The Authors reviewed on some aspects of
      the neurohumoral activation in heart failure, with therapeutic implications.

PMID- 11301913
TI  - Spatial structure and gene flow from biochemical markers in the "Pyrenean Brown"
      breed, a rare cattle race in Catalonia (Spain).

PMID- 11301914
TI  - Structure and genetic relationship among Brazilian naturalized and imported goat
      breeds.
AB  - Fourteen goat populations were studied regarding their genetic relationship and
      structure. Parameters of genetic diversity (HT, HS and GST) and F statistic (FIS,
      FIT and FST) were estimated. Undefined breed populations presented high
      homogeneity, as did imported breed populations. Naturalized breed populations
      showed high differentiation. The genetic distances separating these 14 goat
      populations were calculated from gene frequency data for eight blood genetic
      markers (esterase D, phosphoglucomutase 1, carbonic anhydrase II, peptidase B,
      amylase, haemoglobin, transferrin, and protein X). Working with the genetic
      distance matrix of Nei corrected for small samples (DA), we constructed a
      dendrogram using the unweighted pair group method with arithmetic mean. DA values
      ranged from 0.0027 to 0.1518. The dendrogram divided the populations into two
      groups, one consisting of three populations of naturalized breeds, and another
      including the other populations (imported breeds, undefined breeds and some other
      naturalized breeds).

PMID- 11301915
TI  - Characterization of Nasutitermes globiceps (Isoptera: Termitidae) esterases.
AB  - Esterases of Nasutitermes globiceps termites which occur on the Upper Parana
      River floodplain (Brazil) were characterized. The electrophoretic pattern of the
      termite esterases Nasutitermes globiceps was obtained by starch gel
      electrophoresis. Six esterase activity zones were obtained and numbered, with
      esterase-1 being the most anodall one and esterase-6 the most cathodal one.
      Esterase-2 was detected only with substrates derived from the 4
      methylumbelliferyl radical. The esterases of N. globiceps present wide substrate
      specificity, having been observed with substrates derived from alpha-naphthyl
      (acetate, propionate, and butyrate) and beta-naphthyl (acetate, butyrate) and
      from 4-methylumbelliferyl (acetate, propionate and butyrate). Esterase-6 is a
      caste-specific enzyme detected in soldiers. Only esterases 1, 3 and 5 were
      detected in nymphs. No genetic polymorphism has been detected thus far in the
      esterases of Nasutitermes globiceps. This study suggests that allozyme variation
      can be explored to understand Nasutitermes social structure.

PMID- 11301916
TI  - Isolation and characterization of a cDNA clone coding for a glutathione S
      transferase class delta enzyme from the biting midge Culicoides variipennis
      sonorensis Wirth and Jones.
AB  - Culicoides variipennis sonorensis is the primary vector of bluetongue viruses in
      North America. Glutathione S-transferases (GSTs) are enzymes that catalyze
      nucleophilic substitutions, converting reactive lipophilic molecules into soluble
      conjugates. Increased GST activity is associated with development of insecticide
      resistance. Described here is the isolation of the first cDNA encoding a C.
      variipennis GST. The clone consists of 720 translated bases encoding a protein
      with a M(r) of approximately 24,800 composed of 219 amino acids. The deduced
      amino acid sequence is similar (64%-74%) to class Delta (previously named Theta)
      GSTs from the dipteran genera Musca, Drosophila, Lucilia and Anopheles. The cDNA
      was subcloned into pET-11b, expressed in Epicurian coli BL21 (DE3) and has a
      specific activity of approximately 28,000 units/mg for the substrate 1-chloro-2,4
      dinitrobenzene.

PMID- 11301917
TI  - Sequences of the waxy loci of wheat: utility in analysis of waxy proteins and
      developing molecular markers.
AB  - The waxy proteins from a number of genetic backgrounds of wheat and its
      progenitors were analyzed by SDS-PAGE. The deduced amino acid sequences of the
      waxy proteins of three diploid progenitor species indicated several key amino
      acid substitutions, which could explain the differences observed in the
      electrophoretic mobilities of the wheat waxy proteins. A slight difference
      observed in the apparent molecular weight of the WX-A1 protein of diploid and
      polyploid wheat was explained by amino acid substitutions or variations in
      predicted protein structures. Further, twelve different partial genomic clones,
      representing the individual waxy loci of the various diploid, tetraploid and
      hexaploid wheats, were isolated and compared. The results indicated significant
      variations in intron 4 and led to identification of sequences unique to the
      individual waxy genes and genomes of wheat and its proposed progenitors. The
      sequence variations observed have a great potential for development as molecular
      markers for identification of specific waxy loci and study of the various waxy
      mutants of wheat.

PMID- 11301918
TI  - Blood protein polymorphism in B. frontalis, B. grunniens, B. taurus, and B.
      indicus.

PMID- 11301919
TI  - Potentially traumatizing events in panic disorder and other anxiety disorders.

PMID- 11301920
TI  - Repetitive transcranial magnetic stimulation and electroconvulsive therapy in a
      patient with treatment-resistant schizoaffective disorder.

PMID- 11301921
TI  - Value and effectiveness of consumer advocacy groups: a survey of the anxiety
      disorders support group in South Africa.

PMID- 11301922
TI  - Management of anxiety disorders: the added challenge of comorbidity.
AB  - Patients with anxiety present with a wide variety of disorders that cause
      significant impairment to their everyday lives. To complicate matters, patients
      seldom present with just one anxiety disorder. Such comorbidity, particularly
      where depression is also present, has important implications for both the patient
      and the physician. The patient typically suffers from a greater degree of
      everyday impairment, is more reliant on healthcare services, in particular mental
      health services, and may be at a greater risk of attempting suicide. For the
      physician, comorbidity in anxiety disorders presents a challenge as the patient's
      symptoms are often more severe, present earlier in life, and are frequently
      prolonged which makes their management more complex. This review will focus on
      the anxiety disorders: panic disorder, obsessive-compulsive disorder, social
      anxiety disorder, and post-traumatic stress disorder. The impact of co-existing
      multiple anxiety disorders, depression, or a history of substance abuse will be
      discussed with a view to choosing the appropriate management strategy. Treatment
      options will be reviewed.

PMID- 11301924
TI  - One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety
      disorder in a nationally representative sample.
AB  - Several studies of representative populations have reported prevalence rates of
      DSM-III and DSM-III-R generalized anxiety disorder (GAD); however, no community
      study has examined the effect of the stricter DSM-IV criteria on prevalence
      estimates and patterns of comorbidity. Furthermore, past studies based on
      "lifetime" symptom assessments might have led to upper-bound 1-year and point
      prevalence estimates. Data is presented from a national representative sample
      study of 4,181 adults in Germany, 18-65 years old, who were interviewed for DSM
      IV disorders with the 12-month version of the Munich-Composite International
      Diagnostic Interview. The prevalence rate of strictly defined, 12-month threshold
      DSM-IV GAD was estimated to be 1.5%; however, 3.6% of respondents presented with
      at least subthreshold syndromes of GAD during the past 12 months. Higher rates of
      worrying and GAD were found in women (worrying 10%, GAD 2.7%) and in older
      respondents (worrying 9.3%, TAD 2.2%). Taking into account a wider scope of
      diagnoses than previous studies, a high degree of comorbidity in GAD cases was
      confirmed: 59.1% of all 12-month GAD cases fulfilled criteria for major
      depression, and 55.9% fulfilled criteria for any other anxiety disorder. In
      conclusion, prevalence and comorbidity rates found for DSM-IV GAD are not
      substantially different from rates reported for DSM-III-R GAD. The minor
      differences in our findings compared to previous reports are more likely
      attributable to differences in study methodology rather than changes in
      diagnostic criteria for DSM-IV.

PMID- 11301923
TI  - Heart rate and QT variability in children with anxiety disorders: a preliminary
      report.
AB  - This study compared beat-to-beat heart rate and QT variability in children with
      anxiety disorders (n = 7) and normal controls (n = 15) by using an automated
      algorithm to compute QT intervals. An increase in QT variability appears to be
      associated with a higher risk for sudden cardiac death. A decrease in heart rate
      variability is also linked to significant cardiovascular events. Supine detrended
      QT variability, QT variability corrected for mean QT interval, and QTvi (a log
      ratio of QT variance normalized for mean QT over heart rate variability
      normalized for mean heart rate) were significantly higher in children with
      anxiety compared to controls (P < 0.05). The largest Lyapunov Exponent (LLE) of
      heart rate time series was significantly lower (P < 0.05) in children with
      anxiety compared to controls. These findings suggest a relative increase in
      sympathetic activity and a relative decrease in cardiac vagal activity in
      children with anxiety disorders, and are discussed in the context of the effects
      of tricyclics on cardiac autonomic function in children, and the rare occurrence
      of sudden death during tricyclic antidepressant treatment.

PMID- 11301925
TI  - Characteristics of worry in GAD patients, social phobics, and controls.
AB  - Phenomenological features of worry such as thought content, subjective experience
      of worry, and efforts to control were investigated in the present interview
      study, as well as retrospective information about possible origins. To examine
      the clinical specificity of worrying in Generalized Anxiety Disorder (GAD), 36
      GAD patients were compared to a normal control group (N = 30) and to a clinical
      control group (N = 22 social phobics). GAD patients differed from both groups in
      having higher frequency of worry, higher number of different worry topics, lower
      subjective controllability, more accompanying bodily symptoms, and more distress
      during worry. Thus, in general, our data confirm the central and specific role of
      worrying in GAD. Furthermore, in contrast to other topics, worrying about daily
      hassles was specific to GAD patients, which represents a lower threshold for
      starting to worry.

PMID- 11301926
TI  - Variability and severity of depression and anxiety in post traumatic stress
      disorder and major depressive disorder.
AB  - In order to better characterize the similarities in and differences between the
      nature of the affective disturbance associated with Posttraumatic Stress Disorder
      (PTSD) and with Major Depressive Disorder (MDD), self-reported mood and anxiety
      ratings were examined in PTSD subjects, MDD subjects, and subjects without a
      psychiatric disorder while they were undergoing a chronobiologic study. Based on
      serial ratings on visual analogue scales over a 24 hr period, PTSD subjects
      showed comparable levels of depression as the MDD group, as measured by the mean
      and maximum levels of mood; however, they had greater mood variability, as
      measured by the range and coefficients of variation of the mood ratings. The MDD
      but not the PTSD group had significantly lower mood variability than the non
      psychiatric group, as measured by the coefficients of variation. The PTSD group
      reported higher levels of anxiety than the non-psychiatric or MDD group but
      showed no differences in any measure of variability of anxiety. These findings
      suggest there are phenomenologic differences in the affective symptoms
      experienced by patients with PTSD and with MDD and that mood variability may
      distinguish between them.

PMID- 11301927
TI  - Home tube feeding: an integrated multidisciplinary approach.
AB  - BACKGROUND: Long-term enteral tube feeding is increasingly required by patients
      in the community setting. A previous study of 50 adults on home enteral tube
      feeding in the Dublin area found that some experienced logistical problems and
      many individuals did not choose to seek advice from their GP regarding their tube
      feeding. AIMS: To assess the contribution of health professionals to the care of
      patients on enteral tube feeding in the community. METHODS: GPs and hospital
      dietitians were surveyed using postal questionnaires and nutritional company
      representatives using structured interviews, to assess their involvement with
      patients on home tube feeding. Completed questionnaires were received from 77
      dietitians and 80 GPs. Ten company representatives were interviewed. RESULTS:
      Hospital dietitians carry out most of the initial education and training of
      patients, in addition to the nutritional aftercare. General practitioners tend
      not to be involved, although nutrition specialists working in the nutritional
      products area report encountering patients with tube-feeding complications in the
      community. CONCLUSIONS: Improved co-ordination between hospital and community
      services and more consistent monitoring of those on home enteral tube feeding
      would be an advantage to such patients.

PMID- 11301928
TI  - A prospective study of the workload of a newly formed PEG advice team.
AB  - BACKGROUND: A multidisciplinary advice team may be the optimal way of providing
      the long-term nutritional and percutaneous endoscopic gastrostomy (PEG)-related
      care for patients dependent on PEG feeding but the workload involved is unknown.
      AIM: To study prospectively the workload of a proactive, multidisciplinary PEG
      advice team over a 2-year period. METHODS: Separate documentation from main case
      notes of each episode of the team's contact with PEG or potential PEG patients,
      including assessment, advice and therapy given, from the time of its
      establishment, for four consecutive 6-monthly periods. RESULTS: During the audit,
      89 patients were referred to the team for consideration of PEG insertion and PEGs
      were placed in 74. Eighty-nine additional patients were referred for follow up
      having had a PEG placed elsewhere. During the four audit periods the rate of new
      PEG insertions increased by 53%, the rate of PEG replacements by 315%, and the
      number of patients under the team increased from 16 to 70, an increase of 337%.
      Numbers of inpatient and outpatient consultations, and visits to other
      institutions by members of the team increased commensurately. CONCLUSIONS: The
      rapidly increasing workload of the team suggests it is playing a valued role but
      there are significant resource implications.

PMID- 11301930
TI  - The challenges of innovation in the organization of home enteral tube feeding.
AB  - The number of patients discharged from hospital who need home enteral tube
      feeding has been increasing steadily in the UK. Arrangements for support of these
      patients is extremely variable. The unsatisfactory arrangements for home enteral
      tube feeding which existed in Avon in 1996 prompted an innovative reorganization.
      On the basis of that experience, this review examines the key issues involved and
      the questions to be considered, which may be of benefit to other trusts faced
      with similar challenges.

PMID- 11301929
TI  - Diet-related knowledge, beliefs and actions of health professionals compared with
      the general population: an investigation in a community Trust.
AB  - BACKGROUND: Dietary change is advocated for the prevention and treatment of a
      number of major diseases, and the implicit and explicit assumption is that health
      professionals have a major role in promoting diet change. Previous studies of
      doctors and nurses have shown their knowledge to be inadequate. Other health
      professionals have not been investigated. METHODS: Parts of a questionnaire used
      in a national study of the general public were administered to groups of health
      professionals from a variety of disciplines working in a community Trust. The
      results were compared with those from the study of the general public, for which
      the questionnaire had been devised. RESULTS: 358 questionnaires were completed.
      There was little difference between the knowledge, beliefs and actions of health
      professionals and the general public. CONCLUSION: If health professionals are to
      continue to be expected to promote healthy eating messages there will need to be
      a more systematic approach to their training about nutrition.

PMID- 11301931
TI  - An audit of the theoretical basis of education during dietetic consultations with
      diabetic patients.
AB  - BACKGROUND: This article describes my attempts to reflect my current practice. It
      was conducted in order to determine which of three educational models,
      Empowerment, Motivational Interviewing and Helping People to Change, were being
      used during a diabetic dietetic consultation. METHOD: Analysis of interviews with
      15 patients selected at random from an outpatient clinic was undertaken. Each
      consultation was assessed and relevance to steps in each model noted. RESULTS:
      Overall the results suggest that all three models were used for different
      reasons. Therefore, I conclude that any one of a number of educational approaches
      may be used within a consultation, as there may be elements that overlap. The
      different skills required by each of the models are invaluable at different times
      to assist patients at different phases in their life. CONCLUSIONS: An
      understanding of different educational models is therefore useful and has helped
      to clarify my practice. In future, I anticipate a more formal evaluation of the
      educational process to help identify steps used. These could then be formally
      assessed for their impact on patient outcomes, and so identify specific aspects
      of educational models that assist patient education and help to improve outcomes.

PMID- 11301932
TI  - The effect of age of introduction to lumpy solids on foods eaten and reported
      feeding difficulties at 6 and 15 months.
AB  - AIM: The study aimed to document the dietary patterns of infants and determine
      the development of feeding difficulties as perceived by the mother according to
      the age at which lumpy solids were introduced into the diet. STUDY DESIGN:
      Information was collected from a geographically representative population of 9360
      mothers of infants born in 1991/92, part of the Avon Longitudinal Study of
      Pregnancy and Childhood (ALSPAC). Self-completion questionnaires enquiring about
      the foods and drinks consumed by the infant and any difficulties experienced by
      the mothers in feeding her child at both 6 months and 15 months of age were
      collected. METHODS: Infants were divided into three groups based on the age at
      which they were first introduced to 'lumpy' solids: 10.7% were introduced before
      6 months of age, 71.7% were introduced between 6 and 9 months and 17.6% were
      introduced after 10 months of age. The foods eaten by those introduced before 6
      months and after 10 months were compared to those introduced between 6 and 9
      months. Behaviours and problems as reported by the mother were also assessed.
      RESULTS: Those infants who were introduced to lumpy solids at the earliest ages
      consumed a greater variety of family foods at the age of 6 months, while those
      introduced at 10 months or later had been given fewer solids of all types by 6
      months of age and at 15 months were significantly less likely to be having family
      foods when compared to those introduced between 6 and 9 months. At each age,
      those introduced late (10 months or older) to lumps were more difficult to feed
      and had more definite likes and dislikes. CONCLUSIONS: A significant difference
      was observed in the variety of foods given to infants at both 6 and 15 months
      according to the age at which they began to have lumps in their food, and feeding
      difficulties were more likely to occur when lumps were introduced at or after 10
      months of age.

PMID- 11301933
TI  - A reassessment of the fat intake of children from meat and meat products and an
      estimate of haem iron intakes.
AB  - BACKGROUND: It is possible that fat intake from red meat has declined as a
      consequence of changes in animal husbandry and butchery practices. In particular,
      a study of the intake of vegetarian and meat-eating children concluded that their
      fat intakes were similar, but the most recent information on the fat content of
      meat was not available. In addition, iron availability is probably as important
      as the total amount of iron consumed but estimates of haem iron intake are rarely
      made. METHODS: The dietary intake of 50 omnivorous children was reanalysed to
      produce new estimates of fat and haem iron intakes. Fat intake from meat and meat
      products only was recalculated using supplements to the food tables not available
      to the initial survey. Haem iron intake was calculated by discriminating between
      the different types of meat consumed and estimates of the proportion of iron
      which is in the haem form. RESULTS: The recalculated diets had significantly
      lower energy (8.03-7.50 MJ), fat (79-73 g) and carbohydrate (257-237 g) levels.
      The proportions of energy from fat (36%) and carbohydrate (51%) were unaffected.
      Meat supplied 3.2 mg (33%) of the iron intake (9.6 mg) of which 1.3-1.5 mg (13
      16% of the total) was estimated to be in the haem form. Children may be
      relatively unaffected by the changes in the composition of meat as such, if they
      consume highly processed foods which include, for example, rusk, pastry,
      breadcrumbs and batter. CONCLUSIONS: The original estimates of the intake of fat
      of these omnivorous children from meat and meat products do appear to have been
      overestimates, but only as the weight of fat consumed not as a percentage of
      energy. Haem iron was found to supply a substantial proportion of the iron intake
      of these children and may account for their higher haemoglobin values.

PMID- 11301934
TI  - The alpha and gamma tocopherol levels in serum are influenced by the dietary fat
      quality.
AB  - BACKGROUND: Alpha tocopherol in serum is thought to be of importance in
      protecting lipids against oxidation and low serum levels of alpha tocopherol has
      been suggested to increase the risk for coronary heart disease. However, low
      levels of gamma, rather than alpha, tocopherol have been found in patients with
      manifest coronary heart disease and in populations with a high incidence of
      coronary heart disease. AIM: The aim of this study was to determine the
      tocopherol concentrations in serum after two diets with identical nutrient
      content but with different fat quality, enriched in butter and rapeseed oil-based
      fats, respectively. METHOD: Twenty moderately hyperlipidemic, healthy subjects
      (six females and 14 males) participated in this double-blind cross-over study,
      where two isoenergetic diets were given in a randomized order during two 3-week
      periods, interrupted by a wash-out period of 3-4 weeks. RESULTS: The lipid
      corrected serum concentrations of alpha and gamma tocopherol increased during the
      diet rich in rapeseed oil (by 7 and 23%, respectively) compared with on the
      baseline diet (P < 0.001), while these concentrations decreased (by 5 and 37%,
      respectively, P < 0.01) during the diet rich in saturated fat. The ratio between
      alpha and gamma tocopherol decreased significantly during the rapeseed oil diet (
      23%, P < 0.01) and increased (+46%, P < 0.001) during the butter diet.
      CONCLUSION: Alpha and gamma tocopherol levels in serum are influenced by the type
      of fat used in the diet. The most unexpected finding is that the lipid-adjusted
      gamma tocopherol concentration significantly decreased by 37% during a diet rich
      in saturated fat with an increased ratio between alpha and gamma tocopherol,
      similar to the situation found in CHD patients.

PMID- 11301935
TI  - NHS regions. They were the weakest link.
AB  - The role and autonomy of regional chairs has been eroded since they were
      established in 1974. Regional chairs became increasingly anomalous after the
      abolition of regional health authorities in 1996. In recent years they have been
      caught between the NHS and the civil service. The shift from RHA to an outpost of
      the civil service was profound. Experience as a regional chair suggests that
      really imaginative initiatives come from local enthusiasm rather than top-down
      directives.

PMID- 11301936
TI  - Careless whispers.

PMID- 11301937
TI  - Teaching hospitals. Push me, pull you.
AB  - The Alder Hey Inquiry concluded that trust between Liverpool University and the
      hospital could have avoided the 'worst excesses'. In the past decade policies in
      health and higher education have weakened the long-established mutuality of
      hospitals and universities. Formal partnership arrangements are urgently needed.

PMID- 11301938
TI  - Community health. Home in on the range.

PMID- 11301939
TI  - Data briefing. Health inequality targets.

PMID- 11301940
TI  - The natural history of abdominal aortic aneurysms and their risk of rupture.
AB  - The UK Small Aneurysm Trial has shown that ultrasound surveillance is a safe
      management option for patients with small abdominal aortic aneurysms (4.0 to 5.5
      cm in diameter), with an annual rupture rate of only 1%. We investigated baseline
      risk factors associated with aneurysm rupture in the 1090 trial patients and an
      additional 1167 patients enrolled in the UK Small Aneurysm Study. In this cohort
      of 2257 patients there were 103 cases of aneurysm rupture. After 3 years the
      annual rate of rupture was 2.2% (95% CI 1.7 to 2.8). The risk of rupture was
      independently and significantly associated with female sex (p < 0.001), larger
      initial aneurysm diameter (p < 0.001), current smoking (p = 0.01) and higher mean
      blood pressure (p = 0.01). Age, body mass index, serum cholesterol concentration
      and ankle/brachial pressure index were not associated with an increased risk of
      aneurysm rupture. The most surprising finding was that women had a 3-fold higher
      risk of aneurysm rupture than men. Effective control of blood pressure and
      cessation of smoking are two simple measures that are likely to diminish the risk
      of aneurysm rupture and improve the cardiovascular health of patients with
      abdominal aortic aneurysm.

PMID- 11301941
TI  - Living-related liver transplantation in children at Saint-Luc University Clinics:
      a seven year experience in 77 recipients.
AB  - The Brussels series of living related liver transplantation (LRLT) in 77 children
      (< 15 years) is reviewed. Median (range) recipient age at liver transplantation
      was 1.1 year (0.4-13.1). The main indication for LT was biliary atresia in 55/77
      cases (71%). The living-related donor was one of the parents in 74 instances.
      Hepatic segments 2-3 (n = 67) or 2-3-4 (n = 10) were implanted orthotopically,
      with a median (range) graft weight to recipient body weight ratio of 3.17% (0.91
      8.08). No severe complications or significant long-term sequelae were encountered
      in the living donors. One and five year survival rates were 92% and 89% for the
      patients, and 90% and 86% for the grafts, respectively. The retransplantation
      rate was 2/77 (2.6%), the indication being chronic rejection in both instances.
      In conclusion, LRLT is now a validated procedure in the living donors as well as
      in pediatric recipients with chronic or acute liver diseases. In the current
      context of organ shortage, it provides a valuable alternative to cadaveric LT.

PMID- 11301942
TI  - Ethical aspects of animal experimentation.

PMID- 11301943
TI  - Quality of life assessment after Nissen fundoplication.
AB  - The aim of this study was to evaluate the quality of life of 31 patients
      presenting with gastroesophageal reflux (GORD) and operated on by Nissen
      fundoplication. The series consisted of 23 men and 8 women; the median age was 39
      years (range 22-65) and the median follow-up 36 months (range 18-74). We used a
      new questionnaire: the Gastrointestinal Quality of Life Index (GIQLI) that
      includes 36 items and uses a five-graded Likert scale (from 0 to 4) giving a
      maximum score of 144. This score includes five dimensions: symptoms, emotions,
      vitality, social relations and medical treatment. The pre- and postoperative
      GIQLI scores observed in the Nissen group and the score of a control group of 110
      healthy patients were compared with each other. The preoperative score (71 +/-
      21) was greatly impaired compared to the score (123 +/- 13) of the control group
      (p < 0.0001). The postoperative score (109 +/- 21) increased significantly (p <
      0.0001) but remained statistically inferior to the score of the control group (p
      < 0.005). The analysis of the dimensions showed that the postoperative score of
      the symptoms was lower in the Nissen group: 56 +/- 9 versus 66 +/- 6 in the
      control group (p < 0.0005) whereas no statistical difference was found for the
      four other dimensions. This lower symptoms score was not due to recurrence of
      GORD symptoms but to the occurrence of flatulence and to the persistence of
      gurgling noises and gas bloating. In conclusion, the quality of life of the
      patients requiring surgery for gastroesophageal reflux was greatly impaired, it
      largely improved after Nissen fundoplication but did not reach the level of
      healthy patients because of unrelated GORD gastrointestinal symptoms.

PMID- 11301944
TI  - Laparoscopic colorectal surgery. Analysis of the first 237 cases.
AB  - This study was made to prospectively assess the results of our first 237
      consecutive patients who underwent laparoscopic or laparoscopic-assisted
      colorectal procedures. Between May 1995 and July 1999, two hundred thirty seven
      laparoscopic (assisted) colorectal procedures were performed: 97 sigmoidectomies,
      31 right hemicolectomies, 26 rectosigmoidectomies, 23 abdominoperineal rectum
      amputations and 60 other procedures. The following parameters were recorded and
      analysed: patients gender, age, diagnosis, procedure, conversion to open surgery,
      peroperative and postoperative complications, duration of procedure, mortality
      and length of hospitalization. There were 104 men (44%) and 133 women (56%) with
      a mean age of 62 years. Hundred and fifty-one operations were performed for
      benign indications (diverticular disease (51.6%), benign colonic polyps (17.5%)
      and others (30.9%)) and 86 for cancer (palliative and curative). The conversion
      rate was 4%. Postoperative complications occurred in 65 patients (27%). In 20% of
      these cases re-operation was necessary. The most common cause was bowel
      obstruction. Surgery lasted an average of 110 minutes. Mean overall hospital stay
      was 11 days. Sixty per cent left the hospital within eight days after operation.
      The 60-day mortality rate was 2.9%. The feasibility and safety of laparoscopic
      colorectal surgery has been established in a variety of procedures for different
      indications. Care must be taken in the case of acute diverticulitis which in our
      series is associated with higher minor and major complication rate and conversion
      rate. Although our results for malign cases are good, the definitive incidence of
      neither port-site metastasis nor local recurrence is known and no long-term
      results after laparoscopic surgery for carcinoma are available, we believe that
      curative procedures for cancer should continue to be carried out only within the
      framework of prospective studies unless the patient is more than 75-year old, is
      in bad general condition or when a palliative procedure has to be performed.

PMID- 11301945
TI  - Limy bile and laparoscopic cholecystectomy.
AB  - OBJECTIVE: To determine incidence of 'limy bile' in patients undergoing
      laparoscopic cholecystectomy; to analyze patient characteristics and preoperative
      imaging modalities in these patients and evaluate surgical treatment. PATIENTS
      AND METHODS: A retrospective analysis of 1800 laparoscopic cholecystectomies
      performed between March 1990 and March 1998 for symptomatic gallbladder disease.
      RESULTS: Five patients with limy bile (0.27%) were identified. Four were female
      and one was male, age varied from 42 to 66. Most patients were symptomatic
      longtime before presentation. Ultrasound was not able to differentiate between
      normal gallstones or sludge. In three patients the diagnosis was made before
      operation, in one patient it was an incidental finding. Surgery in these patients
      is not more difficult than in any other patient. CONCLUSION: Limy bile is a rare
      finding (0.27% in 1800 cholecystectomies). Plain abdominal X-rays mostly suggest
      the presence of calcium carbonate precipitate in the gallbladder, but ultrasound
      cannot differentiate between cholelithiasis and limy bile. Laparoscopic resection
      can be performed without problems in most patients. Preoperative diagnosis of
      this rare entity is not essential, as it does not alter treatment.

PMID- 11301946
TI  - Recurrence of gallstone ileus with Crohn's disease.
AB  - Gallstone ileus is an uncommon form of bowel obstruction. It can occur whenever a
      stone passes through the common bile duct or a cholecystoenteric fistula. When a
      stone is in the intestinal track it can either traverse the entire colon to be
      voided spontaneously or obstruct the small or more rarely the large intestine. We
      report a case of recurrence of gallstone ileus in a young patient with Crohn's
      disease. Clinical findings, diagnosis and treatment are presented.

PMID- 11301947
TI  - A first case of Streptococcus bovis bacteremia and peritonitis from endometrial
      cancer origin.
AB  - BACKGROUND: The most important clinical infections caused by Streptococcus Bovis
      are bacteremia and endocarditis. Usually, Streptococcus Bovis bacteremia has been
      described in association with bowel pathology. CASE REPORT: A 67-year-old woman
      with an history of endometrial cancer Ic was admitted with the suspicion of
      peritonitis at examination. At exploratory laparotomy, a total hysterectomy was
      performed and the abdomen was drained. Histology revealed an uterine
      adenocarcinoma staged IIIa with intramyometrial cocci accumulation. Streptococcus
      Bovis was isolated from the peritoneal fluid cultures and three haemocultures.
      CONCLUSION: Because we excluded bowel pathology and endocarditis, this is the
      first case of Streptococcus Bovis bacteremia from endometrial cancer origin.

PMID- 11301948
TI  - Bronchial rupture after direct chest trauma in a child.
AB  - Tracheobronchial injuries are rare in trauma patients, and most often occur after
      motor vehicle accidents. Occasionally, other mechanisms cause airway disruption.
      The pliability of the chest wall in children greatly adds to the differences in
      injuries when compared with adult trauma patients. We present the case of a six
      year old girl with an isolated right-sided bronchial rupture after direct trauma
      to the chest.

PMID- 11301949
TI  - A rare complication of miliary tuberculosis: intestinal perforation.
AB  - Small bowel perforation is a rare complication of miliary tuberculosis. We report
      the case of a 21-year old patient who developed a small bowel perforation 70 days
      after the initiation of adequate tuberculosis treatment. We also present a review
      of the literature.

PMID- 11301950
TI  - Are infra-inguinal angioplasty and surgery comparable?
AB  - PURPOSE: The indications for Percutaneous Transluminal Angioplasty (PTA) in the
      treatment of infrainguinal peripheral arterial occlusive disease are
      controversial. We have attempted to provide up to date data and compare the
      techniques of both conservative management and surgical approaches. REVIEW
      UNDERTAKEN: A literature review was undertaken after using the Medline database
      and an Ovid-based search engine on the Internet. The most recent reviews, meta
      analyses and studies contributing the highest levels of evidence available were
      reviewed and cross-referenced. EVIDENCE: The suitability of femoropopliteal
      disease for treatment with PTA depends on the severity of the patient's
      presentation and the extent of disease. Given the optimal pattern of disease, PTA
      can have equivalent initial technical success and medium term patency rates with
      the obvious advantages of lower in-hospital mortality, shorter hospital stay and
      lower inpatient costs. However, PTA has a higher secondary procedure rate and
      this negates many of the perceived benefits. In critical limb ischaemia (CLI)
      many lesions are unsuitable for PTA and require surgical procedures for limb
      salvage. Patients selected for the trials are often not from strictly stratified
      groups. These selection biases often interfere with direct comparison between the
      two techniques in all but a few prospective randomised-control studies.
      CONCLUSIONS: There is still a lack of high level evidence to draw a consensus on
      the place for PTA in femoropopliteal occlusive disease. It is apparent that the
      most appropriate lesions make up only a small percentage of patient
      presentations. When limb salvage is required it is often a situation only
      amenable to surgical bypass and this is why the two techniques are not easily
      comparable.

PMID- 11301951
TI  - Health plans and handhelds.

PMID- 11301952
TI  - Stats & facts. Physician office visits getting longer, even in MCOs.

PMID- 11301953
TI  - Coming soon: interactive television and T-commerce.

PMID- 11301954
TI  - Eye care providers in managed care.
AB  - The integrated relationship and roles in managed care of ophthalmologists,
      optometrists, and opticians have changed profoundly in recent years. The change
      is in part the result of the advancement of optometric education and license in
      the diagnosis and treatment of ocular disease. The change has also evolved
      because of the influence of managed care and its objective to reduce costs while
      elevating quality of care. The authors explain that vertical integration of all
      ophthalmic services, ranging from eye examination to eyeglass dispensing to
      ocular surgery, can help MCOs maximize quality and minimize costs.

PMID- 11301955
TI  - E-health--where we're going and how we'll get there.

PMID- 11301956
TI  - Emerging technologies in health care and the patient encounter of the future.
AB  - In the last five years, the Web has changed the way information is disseminated,
      knowledge is gained, and health care is provided. Even though the health care
      industry has yet to fully realize the potential of the Internet, the Web is only
      the beginning. Several emerging technologies will be changing the rules again.
      With new forms of network connectivity and faster, new wireless technologies, the
      adoption rate of mobile, handheld computers in health care will grow feverishly.
      Intelligent, autonomous software agents that guide the patient through the
      continuum of care will extend the reach of health care providers to all places at
      all times. The author discusses these new concepts, how they might be applied in
      health care, and the doctor-patient health care transaction.

PMID- 11301957
TI  - Massachusetts, managed care reform, and the defeat of Ballot Question 5.
AB  - On Election Day 2000, Massachusetts voters were faced with a ballot initiative
      that would have made such topical proposals as an MCO patient's bill of rights,
      HMO regulation, and examination of the conversion of nonprofit health
      institutions to for-profit status into state law. The author, who watched the
      struggle between pro- and anti-initiative forces from close range, describes the
      events and ramifications of the decision that voters finally made.

PMID- 11301958
TI  - Achieving desired outcomes in an acute care environment.

PMID- 11301959
TI  - Integrating end-of-life care with disease management programs: a new role for
      case managers.
AB  - Case managers are crucial to any well-designed disease management program. 
      However, in the progressive course of serious illness, patients, their families,
      and MCOs need the skills of case manager more than ever to help them through end
      of-life care choices.  The author describes what case managers will need in their
      "toolbox" to provide insight to these health plan members.

PMID- 11301960
TI  - Considerations in the treatment of mild-to-moderate hypertension.

PMID- 11301961
TI  - A retrospective analysis comparing the costs and cost effectiveness of amlodipine
      and enalapril in the treatment of hypertension.
AB  - A comparison of treatment costs and cost effectiveness was performed
      retrospectively by using patient-level data from a randomized, controlled, one
      year clinical trial of amlodipine and enalapril in the treatment of mild-to
      moderate hypertension. Unit costs of amlodipine and enalapril were applied to the
      daily dosages of individual patients to calculate the total costs and average
      costs per patient in each treatment group in the clinical trial on an intent-to
      treat basis. Efficacy rates were used to calculate the average treatment costs
      per success in blood pressure control. Although not statistically significant,
      amlodipine treatment resulted in a higher efficacy (89.5%) vs. enalapril (85.2%).
      The average costs per amlodipine-treated patient were consistently lower (
      $112.30) than for the enalapril-treated patient by week 50. Treatment with
      amlodipine resulted in an average cost per success of $609 per patient compared
      with $772 per enalapril-treated patient. A sensitivity analysis revealed that, in
      the treatment of mild-to-moderate hypertension over the 50-week treatment period,
      amlodipine would remain less costly than enalapril, with a decrease in the cost
      of enalapril of up to 17%, and would remain more cost effective, with a 21%
      decrease in the cost of enalapril.

PMID- 11301962
TI  - Working to reduce infant mortality in a managed Medicaid population.
AB  - Infant mortality and low-birthweight delivery are particularly prevalent in
      Medicaid populations. In Philadelphia, Medicaid managed care plans, state and
      city agencies, advocacy groups, and Ob/Gyn providers joined together to build a
      comprehensive database on which prenatal care frequency and quality performance
      can be measured.

PMID- 11301963
TI  - Private LTC insurance. The home care claimant experience.
AB  - An understanding of claimants and their behavior should help consumers make more
      informed choices about financing their potential LTC needs, help the private
      insurance industry better meet those needs, and inform public policies designed
      to support and regulate the market. To this end, LifePlans, Inc. and the Center
      for Health and Long-Term Care Research conducted in-person interviews with more
      than 1,000 private long-term care insurance claimants residing both in the
      community and in institutions.

PMID- 11301964
TI  - The challenge. Protecting consumers. Alleviating public burdens.
AB  - The Private Long Term Care Insurance Conference is the only conference of its
      kind, bringing together individuals from the public and private sectors, the for
      profit and not-for-profit worlds, and from a myriad of consumer and provider
      organizations, to discuss and debate long-term care and the role of insurance. No
      other national meeting provides an opportunity for these groups to come together
      to discuss ways the private market and government can work together to meet
      consumer need and reduce public Medicaid expenditures.

PMID- 11301965
TI  - The nuts & bolts of LTC insurance coverage for home care.
AB  - Understanding long-term care insurance coverage is no easy task. Using this basic
      guide, consumers and providers can gain a better sense of what their policies
      offer.

PMID- 11301966
TI  - Problems with LTC coverage. A provider perspective.
AB  - A lack of coordination exists between the LTC insurance industry and the
      providers and recipients of home care. The claims process must be simplified, and
      we in home care must work to change perceptions among both those we serve now and
      those who will need us as they and other baby boomers reach their retirement
      years.

PMID- 11301967
TI  - Partnership insurance. An innovation to meet LTC financing needs.
AB  - In the mid-1980s, the Robert Wood Johnson Foundation (RWJF) began to explore ways
      to support state-based initiatives in long-term care financing. This exploration
      has resulted in an innovative public-private long-term care insurance program
      known as the Partnership for Long-Term Care.

PMID- 11301968
TI  - The new navigators. Geriatric care managers forge paths for clients.
AB  - Long-term care needs are evolving in unforeseen ways. Successful aging in place
      is a primary concern for baby boomers and their parents. Medical advances,
      coupled with the complex health care delivery systems, present unique challenges
      for the consumer. Increasingly, the changing demographics of our society are
      placing new demands on these systems. Seniors and their families are taking a
      proactive stance, seeking health care advocates to assist them with need
      assessments, treatment recommendations, planning, and support services.

PMID- 11301969
TI  - Tax rules on long-term care insurance generate new headaches for consumers.

PMID- 11301970
TI  - Establish meaningful standards for private LTC insurance.

PMID- 11301971
TI  - Reinventing health insurance.

PMID- 11301972
TI  - LTC insurance. Changing dynamics, differing perspectives.
AB  - Many have challenged the best minds in the industry in designing and pricing long
      term care (LTC) insurance. Marketing LTC insurance requires a thorough
      understanding of public policy issues and programs in addition to exceptional
      business expertise. However, the results have been worthwhile. Today, the market
      offers affordable products with solid benefits. Not only can LTC insurance
      protect individual lifestyles and savings, it can also reduce burgeoning state
      and federal Medicaid spending.

PMID- 11301973
TI  - [Which antihypertensive agents are best? Results of two new meta-analyses are
      enriching but don't stop the discussion].

PMID- 11301974
TI  - [Local differences when it comes to average length of life in Sweden. Shortest
      lifespan of women is in industrial regions and of men in big cities].

PMID- 11301975
TI  - [Skin of the aging human being].
AB  - Cutaneous aging includes true aging and photo-aging due to sun exposure. A
      decrease in epidermal turnover rate results in epidermal atrophy and delayed
      wound-healing. A reduction in the number of epidermal Langerhans' cells is
      responsible for a decrease in delayed immune responsiveness in skin observed in
      the elderly. Reduced numbers of fibroblasts and mast cells are typical histologic
      findings in aging human dermis. Collagen bundles become fragmented, less elastic
      and more brittle. Telomere shortening at the end of chromosomes is probably the
      major mechanism of cellular senescence in skin. Common skin tumors and other
      major age-related changes in the skin of the elderly are described.

PMID- 11301976
TI  - [Quality assured images in mammographic screening. Assessment criteria as a basis
      for national guidelines].

PMID- 11301977
TI  - [The Gothenburg study of women and alcohol: low occurrence of abuse--increase
      appears to have abated].
AB  - Prevalence of alcohol dependence and abuse (ADA) was determined in a cohort of
      women selected by stratified random sampling from the general population in
      Gothenburg. A questionnaire was administered to 3,130 women and 399 were
      interviewed. Questions were asked about social background, living conditions,
      family and working life. Volume and frequency of alcohol intake were recorded,
      and diagnoses were made according to DSM-III. We found that the one-year
      prevalence of ADA was 1.5 percent and the life time prevalence 3.3 percent. In a
      follow-up five years after base-line, the prevalence of ADA was unchanged, while
      indicators of high alcohol consumption and high episodic drinking showed reduced
      levels of problem drinking.

PMID- 11301978
TI  - [The Gothenburg study of women and alcohol: problems during childhood and
      adolescence important risk factors].
AB  - This is a part of longitudinal study concerning women and alcohol in Gothenburg.
      The aim was to find out more about risk factors for alcohol dependence and abuse
      (ADA) among women in the general population, as well as social conditions and
      life style among these women. Several indicators of dissatisfactory childhood
      conditions, and particularly sexual abuse before age 13, were related to ADA in
      adulthood. Early substance abuse, such as having been intoxicated before age 15
      and having used narcotics before 18, was strongly related to future ADA. Our
      findings point to the need of paying attention to mental health problems in
      childhood and youth, and to prevent early use of alcohol and drugs.

PMID- 11301979
TI  - [Rollerblading and skateboarding injuries among children in Bergen, Norway].
AB  - BACKGROUND: The popularity of rollerblading and skateboarding activities in
      Norway is reflected in the number of injuries seen at our casualty centres and
      hospitals. MATERIAL AND METHODS: During 1998, we made a prospective registration
      of 7,041 new injuries involving children below the age of 16 treated at the
      Accident and Emergency Department and at Haukeland University Hospital in Bergen.
      RESULTS: Rollerblading and skateboarding injuries accounted for 113 cases,
      representing 1.6% of all injuries. Three quarters were boys, nine out of ten were
      10 to 15-year-olds, and arms/hands were injured in two thirds of the cases.
      Almost two thirds of the injuries were fractures (n = 67), representing a higher
      fraction than seen in other activities. Most of them were distal radial fractures
      (n = 39), but scaphoid fractures, an otherwise seldom child fracture, were seen
      in one tenth (n = 6) of all fractures. INTERPRETATION: Scaphoid fractures can,
      when untreated, cause pseudarthrosis; this should be borne in mind when treating
      children with hand pain after fall on their rollerblades or skateboards. As
      fractures of the hand root and wrist accounted for 40% of all injuries, hand and
      wrist protection seem to be the best preventive measure in terms of number of
      injuries.

PMID- 11301980
TI  - [Hazardous--but healthy. New leisure activities and sports result in increased
      number of new and more severe injuries].

PMID- 11301981
TI  - [Comment for the debate on DAMP: evidence requirements create problems in the
      process].

PMID- 11301982
TI  - [What happened with the "Health for All by the year 2000"? A medical student
      reports from People's Health Assembly].

PMID- 11301983
TI  - [The National Board of Health and Welfare on fixed physician-patient contacts in
      primary health care: deviations from requirements for specialists in general
      practice need legislative changes].

PMID- 11301984
TI  - [Estrogen during and after climacteric--problems and possibilities for primary
      health care].

PMID- 11301985
TI  - [Neuropsychiatry and reductionism].

PMID- 11301987
TI  - [Meaninglessness and medicine--comment to a book review].

PMID- 11301986
TI  - [Concerning private practice and private time].

PMID- 11301988
TI  - [Citanest recalled--bad and inconsistent decision by Astra pharmaceutical
      company].

PMID- 11301989
TI  - [The SBU-report on back pain: weakly documented etiology].

PMID- 11301990
TI  - Ecstasy crackdown. Will the feds use a 1980s anti-crack law to destroy the rave
      movement?

PMID- 11301991
TI  - The Tylenol scare.

PMID- 11301992
TI  - Don't lose sleep.

PMID- 11301993
TI  - Bush moves on two fronts to tighten UPL (upper payment limit) loophole.

PMID- 11301994
TI  - Human cloning efforts stimulate legislative response.

PMID- 11301995
TI  - Perspectives. Little bang for buck in coverage credits for firms.

PMID- 11301996
TI  - Social Security fixes--beware of conjurers!
AB  - Among the many proposals for reform, there is one that offers the best chance of
      truly solving Social Security's financial problems, these authors believe. That
      proposal would increase savings by requiring workers to invest an additional 2%
      of their covered wages in individual accounts. At retirement, 75% of the money
      would go toward buying the current level of Social Security benefits, and 25%
      would be given to the individual as an "extra" pension. Individuals, not the
      government, would control investment of these accounts.

PMID- 11301997
TI  - Characteristics of successful wellness programs.
AB  - Wellness programs have proved to be an effective tool to use in reining in health
      care costs. This author describes successful wellness programs and shows that
      these programs not only improve the bottom line for employers or Taft-Hartley
      funds, but they also help employees feel better about themselves and more
      positive about the organization they work for.

PMID- 11302000
TI  - Strengthening Social Security.
AB  - Social Security's core protections must be maintained, according to this author.
      He believes that by creating universal savings accounts and investing a small
      portion of the Social Security trust fund in equities, it is possible to secure
      the long-term future of Social Security without subjecting workers to the risks
      of individual, private accounts.

PMID- 11302001
TI  - An update on legal aspects of plan communications.
AB  - Plan communications can be a real challenge for trustees, unions and management,
      but effective communications are essential because they provide the link between
      plan sponsors' efforts to provide benefits and the actual receipt of those
      benefits by participants. Communication-related issues that must be considered by
      those responsible for keeping plan participants informed include ERISA
      provisions, the need for accurate information, disclosures concerning possible
      benefit plan changes, COBRA rights and HIPAA provisions.

PMID- 11302002
TI  - Social Security must be reformed.
AB  - Today's Social Security system must be reformed not only because it will soon be
      in financial crisis but also because it is simply a bad deal for most Americans,
      this author believes. She argues that it should be transformed into a system of
      personal retirement accounts and uses the example of San Diego, which opted out
      of Social Security in 1981 and replaced it with a mandatory defined contribution
      program for city employees, to show the benefits of private accounts.

PMID- 11302003
TI  - Plasma homocysteine and microvascular complications in type 1 diabetes.
AB  - BACKGROUND: Homocysteine is involved in a complex and dynamic system of vascular
      injury and repair and may thus contribute to the development of diabetic
      microangiopathy. This still debated issue has important scientific and clinical
      implications, since hyperhomocysteinemia can be corrected nutritionally. AIMS: 1)
      To evaluate the association between fasting plasma homocysteine, type 1 diabetes
      and its microvascular complications; 2) to elucidate the basis of this
      association by investigating the major determinants of plasma homocysteine in
      relation to diabetic microangiopathy. METHODS: We studied sixty-six consecutive
      patients with type 1 diabetes mellitus of > 10 years duration and normal serum
      creatinine (< 115 mumol/L, 1.3 mg/dL), and free from clinically detectable
      cardiovascular diseases. Forty-four non-diabetic controls were also studied.
      Plasma concentrations of homocysteine, folate and vitamin B12 were investigated
      together with the C677T mutation in the gene coding for methylenetetrahydrofolate
      reductase (MTHFR), a key enzyme in homocysteine metabolism. Renal and retinal
      diabetic complications were evaluated as albumin/creatinine ratio on early
      morning, urine spot collection and fundus photographs. FINDINGS: Fasting plasma
      homocysteine levels were very similar in patients and controls. Patients with
      microalbuminuria or proliferative retinopathy had significantly higher values
      than those without: 9.4 +/- 3.1 vs 7.4 +/- 2.8 mumol/L, p < 0.02 and 9.5 +/- 2.6
      vs 7.3 +/- 3.0 mumol/L, p < 0.05. This difference was not attributable to
      confounders, such as age, sex and smoking, nor to dissimilar plasma folate and
      vitamin B12 concentrations. In contrast, homozygosity for the C677T mutation in
      the MTHFR gene--the commonest genetic defect linked to moderately increased
      plasma homocysteine--was significantly more frequent in patients with
      microalbuminuria and/or proliferative retinopathy (50% vs 13%, p < 0.004), odds
      ratio 6.7 (95% CI 1.7-27.6). CONCLUSIONS: Type 1 diabetes as such is not
      associated with increased plasma homocysteine levels, though patients with
      microalbuminuria and/or proliferative retinopathy display significantly higher
      values than those without. This difference is not attributable to obvious
      confounders, nor to differences in vitamin status, and may be partly mediated by
      genetic factors. Plasma homocysteine, together with other diabetes-related noxae,
      may thus be in a position to contribute to the development of nephropathy and the
      progression of retinopathy.

PMID- 11302005
TI  - Apolipoprotein H is increased in type 2 diabetic patients with microalbuminuria.
AB  - BACKGROUND AND AIM: Serum apolipoprotein H (Apo H) levels are increased in
      hyperlipidemic subjects and type 2 diabetics, but unknown in microalbuminuria,
      another disorder with an increased cardiovascular risk. We looked to see whether
      increased Apo H levels are associated with microalbuminuria in type 2 diabetes.
      METHODS AND RESULTS: Serum Apo H was calculated in 20 normoalbuminuric and 17
      microalbuminuric type 2 diabetics matched for age, sex, body mass index (BMI),
      glycosylated haemoglobin, plasma lipids and duration of diabetes, and also
      compared with 20 non-diabetic controls matched for age, sex, BMI and plasma
      lipids. Mean serum Apo H was significantly higher in the microalbuminuric
      patients (31.12 +/- 1.58 SEM vs 25.25 +/- 1.52 and 24.72 +/- 0.99 mg/dL, p =
      0.003). CONCLUSION: Serum apo H levels are increased in type 2 diabetics with
      microalbuminuria.

PMID- 11302004
TI  - Impact of the new American Diabetes Association and World Health Organisation
      diagnostic criteria for diabetes on subjects from three ethnic groups living in
      the UK.
AB  - BACKGROUND AND AIM: The American Diabetes Association (ADA) recommends basing
      diabetes diagnosis on a fasting plasma glucose (FPG) of > or = 7.0 mmol/L and
      impaired fasting glucose (IFG) on 6.1 < or = FPG < 7.0 mmol/L. The new World
      Health Organisation (WHO) recommendations also adopt this FPG cut-off, but retain
      the oral glucose tolerance test (OGTT) where possible and the intermediate group
      of impaired glucose tolerance (IGT) in addition to IFG. We compare the effect of
      the new ADA and WHO diagnostic criteria in three ethnic groups. METHODS AND
      RESULTS: Three hundred and eighty whites, 340 South Asians and 347 subjects of
      African descent, aged 40-59 years and not known to have diabetes, were identified
      through South London general practices. Inevitably, the prevalence of new
      diabetes was lower under ADA than under WHO criteria (including post-load levels)
      for all three groups, falling from 5.7% overall to 3.3% (fall 2.4% 95% CI 1.6% to
      3.6%). The largest fall was for South Asians from 9.1% to 5.0% (fall 4.1% 95% CI
      2.2% to 6.8%). The prevalence of impaired glucose homeostasis under ADA criteria
      (IFG) was substantially less than under WHO criteria (IFG + IGT). Under WHO
      criteria, including a glucose tolerance test, there was marked variation by
      ethnic group in diabetes prevalence (p < 0.001) and IGT (p < 0.0001), both were
      most prevalent amongst South Asians. Under ADA criteria, (or new WHO criteria
      without OGTT) diabetes prevalence still differed significantly between groups (p
      < 0.01), but there was no difference in IFG prevalence (p = 0.43). CONCLUSIONS:
      Subjects with IGT but normal FPG are at greater risk of coronary heart disease.
      The new ADA definition fails to identify substantial numbers of such subjects,
      particularly among South Asians. Our study supports the retention of the OGTT in
      the new WHO criteria, particularly for South Asians.

PMID- 11302007
TI  - Effect of Norwegian fish powder on risk factors for coronary heart disease among
      hypercholesterolemic individuals.
AB  - BACKGROUND AND AIM: Numerous studies suggest an association between high intake
      of fatty fish and reduced risk of coronary heart disease. Very long-chain omega-3
      fatty acids are thought to be responsible for the benefits observed, though other
      fatty fish components may act in concert with them. Norwegian fish powder is a
      dry herring product that contains essential amino acids, marine omega-3 fatty
      acids, vitamins and minerals. The aim of the present study was to determine
      whether it has beneficial effects on risk factors for coronary heart disease in
      man. METHODS AND RESULTS: A single center, randomized, double-blind, parallel
      treatment study was carried out for 12 weeks. Subjects with primary
      hypercholesterolemia were randomly allocated to 10 g fish powder or placebo (20
      tablets/day). Participants were instructed to follow National Cholesterol
      Education Program (NCEP) Step I Diet during a 4-week diet run-in phase and during
      the study. Concentrations of lipids, lipoproteins, hemostatic variables and
      endothelial cell markers were determined before and after supplementation. Our
      data showed that the fish powder supplement was well tolerated. A significant
      decrease and increase respectively were observed in plasma alpha-linolenic acid
      (p = 0.03) and docosahexaenoic acid (DHA) (p = 0.03). Concentrations of lipids,
      lipoproteins, homocysteine, factor VII, fibrinogen, tissue plasminogen activator
      (tPA), plasminogen activator inhibitor (PAI)-1, soluble intercellular adhesion
      molecule (ICAM)-1, P-selectin and interleukin (IL)-8 were not beneficially
      affected. CONCLUSIONS: Fish powder supplementation does not seem an effective
      approach to improve risk factors for coronary heart disease in
      hypercholesterolemic subjects following the NCEP Step I Diet.

PMID- 11302006
TI  - Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo
      controlled trial.
AB  - BACKGROUND AND AIM: Postmenopausal modification of the lipid profile plays a
      major role in the risk of ischemic heart disease. Lifestyle counseling and
      estrogen replacement therapy have all been proposed as first-line measures, but
      there is no agreement on the best way to treat climacteric dyslipidemia. Soybean
      based diet seems particularly attractive in this context, given its cholesterol
      lowering potential, its hypothetical anticancerous effects and possible
      modification of climacteric symptoms. METHODS AND RESULTS: We evaluated the
      effect of 60 g isolated soy protein (ISP) daily on the lipid profile of 104
      postmenopausal women (53.3 +/- 3.3 years) in a double-blind, parallel, placebo
      controlled (caseinate) trial, as part of a broader assessment of the effect of
      ISP on climacteric symptomatology. Serum total cholesterol, LDL-cholesterol, HDL
      cholesterol, triglycerides, apo A-I, apo B and lipoprotein (a) were determined
      before and after a 12-week diet modification. Seventy-seven women completed the
      trial. Both soy and placebo determined a significant reduction in total
      cholesterol (-0.42 +/- 0.79 and -0.40 +/- 0.57 mmol/L) and LDL-cholesterol (-0.35
      +/- 0.72 and -0.31 +/- 0.54 mmol/L), but only soy had a significant lowering
      effect on apo B and the LDL-cholesterol/HDL-cholesterol ratio (-6% and -8% from
      baseline respectively); lipoprotein (a) plasma levels were not significantly
      changed by either treatment. Forty-four women were dyslipidemic at baseline;
      those with increased LDL concentrations showed a somewhat greater improvement in
      their lipoprotein profile (LDL-cholesterol and apo B reduction) with soy rather
      than placebo. No further information emerged when the subjects were divided into
      three apo E phenotypes. CONCLUSIONS: We conclude that diet supplementation with
      60 g ISP is slightly better than caseinate in favorably modifying the lipoprotein
      metabolism of postmenopausal women; this effect is more evident in
      hypercholesterolemic subjects.

PMID- 11302008
TI  - Partial resistance of low density lipoprotein to oxidation in vivo after
      increased intake of berries.
AB  - BACKGROUND AND AIM: The health-promoting effects of fruit- and vegetable-based
      diets are known to be associated with their antioxidative components. We found in
      our preliminary in vitro laboratory tests that extracts of many common Finnish
      edible berries are potent scavengers of peroxyl radicals and inhibitors of lipid
      peroxidation. We therefore designed the current study to evaluate both the long
      term (8 weeks) and short-term (5 hours) effects of increased intake of three
      berries on antioxidant potential and lipid peroxidation. METHODS AND RESULTS:
      Healthy 60-year-old men were randomized to berry, supplement and control groups
      (20 men in each group). The berry group ate, in addition to their normal diet, a
      100 g portion of deep-frozen berries (bilberries, lingonberries, or black
      currants) daily for 8 weeks. The other groups ingested daily 100 mg of alpha
      tocopherol and 500 mg of ascorbic acid (supplement group) or 500 mg of calcium
      gluconate (control group). In the short-term experiment 6 men ate 80 g of each of
      the three berries in one go. Serum ascorbate concentrations increased
      significantly in both the berry and the supplement group. Serum alpha-tocopherol
      levels and the antioxidant potential (TRAP) in low density lipoprotein (LDL)
      increased in the supplement group only. In the berry group, slightly lowered LDL
      diene conjugation (p = 0.074) and slightly increased total serum TRAP (p = 0.084)
      values were observed. No changes were found in these measures in the supplement
      or the control group. In the short-term experiment, LDL TRAP showed a small
      increase (about 10%, p = 0.039) during five hours after the intake of 240 g
      berries. CONCLUSIONS: The effects of consumption of berries on antioxidant
      potential and diene conjugation in LDL particles in vivo appear to be small.

PMID- 11302010
TI  - Causality assessment of adverse events following immunization.

PMID- 11302009
TI  - Dietary lipoic acid supplementation prevents fructose-induced hypertension in
      rats.
AB  - BACKGROUND AND AIMS: In fructose-induced hypertension in Wistar-Kyoto (WKY) rats,
      excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, alter
      membrane Ca2+ channels and increase cytosolic free calcium and blood pressure.
      The thiol compound N-acetyl cysteine prevents such hypertension by binding these
      aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The
      aim of this work was to investigate whether dietary supplementation of an
      endogenous fatty acid, alpha-lipoic acid, another thiol compound known to
      increase cysteine and glutathione, prevents this hypertension and its associated
      biochemical and histopathological changes. METHODS AND RESULTS: Starting at seven
      weeks of age, animals were divided into three groups of six animals each and
      treated as follows: control (normal diet and normal drinking water); fructose
      (normal diet and 4% fructose in drinking water); fructose + lipoic acid (diet
      supplemented with lipoic acid 500 mg/kg feed and 4% fructose in drinking water).
      After 14 weeks, systolic blood pressure, platelet [Ca2+]i, plasma glucose and
      insulin and kidney and aortic aldehyde conjugates were significantly higher in
      the fructose group. These also displayed smooth muscle cell hyperplasia in the
      small arteries and arterioles of the kidneys. CONCLUSION: Dietary alpha-lipoic
      acid supplementation in fructose-treated WKY rats may prevent their increase in
      systolic blood pressure by normalizing cytosolic [Ca2+], blood glucose and
      insulin, kidney and aortic aldehyde conjugates and preventing adverse renal
      vascular changes.

PMID- 11302011
TI  - Roll back malaria.

PMID- 11302012
TI  - HCFA proposes modifications to verification of compliance policy.

PMID- 11302013
TI  - A dozen ways you can improve your facility's employee recruitment and retention
      efforts.

PMID- 11302014
TI  - Lawmakers introduce bills to reform HCFA appeals process.

PMID- 11302015
TI  - Family: our greatest strength.

PMID- 11302016
TI  - World AIDS Day observed around the globe.

PMID- 11302017
TI  - Russia has world's fastest growing HIV/AIDS epidemic.

PMID- 11302018
TI  - African leaders call for urgent action to address pandemic.

PMID- 11302019
TI  - 40 percent of US citizens do not know how HIV is transmitted.

PMID- 11302020
TI  - Iran bans tattoos.

PMID- 11302021
TI  - STD conference looks at rise in gonorrhea among gays.

PMID- 11302023
TI  - Canada to begin screening immigrants for HIV.

PMID- 11302022
TI  - Uganda cuts AIDS drug deal.

PMID- 11302024
TI  - Red Cross called to task for its handling of blood products.

PMID- 11302025
TI  - US adopts needlestick injury prevention law.

PMID- 11302026
TI  - UNICEF: China moving on a fast track to AIDS.

PMID- 11302027
TI  - South Africa cuts agreement for one AIDS drug but ignores another.

PMID- 11302028
TI  - Election 2000: a new administration steps up to the plate.

PMID- 11302029
TI  - The cost of living.

PMID- 11302030
TI  - Starting, stopping, picking, and switching antiretrovirals or, the ring in the
      river. Glasgow: Part 2.

PMID- 11302031
TI  - Coordination of analytic and similarity-based processing strategies and expertise
      in dermatological diagnosis.
AB  - BACKGROUND: Medical diagnosis may be thought of as a categorization task.
      Research and theory in psychology as well as medical decision making indicate at
      least 2 processes by which this categorization task may be accomplished: (a)
      analytic processing, in which one makes explicit use of clinical features to
      reach a diagnosis, and (b) similarity-based processing, in which one makes use of
      past exemplars to reach a clinical diagnosis. Recent research indicates that
      these 2 processes are complementary. PURPOSE: We investigate the coordination of
      analytic and similarity-based processes in clinical decision making to examine if
      the relative reliance on these 2 processes is (a) amenable to instruction and (b)
      dependent on level of clinical experience. METHODS: The reliance of these 2
      processes was indexed by the performance of 12 preclinical medical students on
      cases dichotomized as typical and atypical (analytic processing) and on cases
      dichotomized as similar or dissimilar to cases seen previously in a training
      phase (similarity-based processing). RESULTS: The results indicated that both
      processes are operative. Of particular interest was that preclinical medical
      students enhanced their performance by adopting a similarity-based strategy. This
      was especially so for atypical cases. These results are in contrast to residents,
      who enhanced their performance by adopting an analytic strategy. CONCLUSIONS: The
      relative reliance on analytic and similarity-based processes is amenable to
      instruction and dependent on expertise.

PMID- 11302032
TI  - Understanding and improving medical student specialty choice: a synthesis of the
      literature using decision theory as a referent.
AB  - BACKGROUND: As emphasis in medicine has shifted to increasing the number of
      physicians who choose primary care specialties, many studies of medical specialty
      choice have been conducted. Although researchers have approached the topic in a
      number of ways, most approaches have tended to focus on narrow elements of the
      choice, such as the effect of programs or curricula. A more comprehensive
      approach is possible by fitting the process to a preexisting broad theoretical
      framework. SUMMARY: This synthesis of the literature examines specialty choice
      from the perspective of decision theory--with its aims of understanding how
      decisions are made, providing information about the quality of decisions, and
      improving the decision-making process. CONCLUSION: This approach has the
      potential to not only help deconstruct the process of decision making regarding
      specialty choice but also uncover information about the best ways to help medical
      students learn to make wise decisions.

PMID- 11302033
TI  - Using a Lego-based communications simulation to introduce medical students to
      patient-centered interviewing.
AB  - PURPOSE: Teaching patient-centered interviewing skills to medical students can be
      challenging. We have observed that 1st-year medical students, in particular, do
      not feel free to concentrate on the interviewing skills because they are
      preoccupied with complicated technical medical knowledge. The Lego simulation we
      use with our 1st-year students as part of a professional-skills course overcomes
      that difficulty. SUMMARY: The Lego activity is a role play analogous to a doctor
      patient interview that uses identical sets of Legos for the "doctor" and for the
      "patients" and a small construction that represents a patient history.
      CONCLUSIONS: With a simple questionnaire, data were collected from students at
      different points during instruction. Results indicate that the Lego activity was
      very effective in helping students learn the importance of open-ended
      questioning. It also was rated as highly as the very dynamic interactive part of
      the instructional session. The effectiveness of the Lego activity may be due to
      the properties of analogies.

PMID- 11302034
TI  - A survey of student assessment in U.S. medical schools: the balance of breadth
      versus fidelity.
AB  - BACKGROUND: Faced with the challenge to develop models of assessment relevant to
      work of physicians, medical schools have broadened their assessment of medical
      student competency. PURPOSE: U.S. medical schools were surveyed to determine the
      extent to which student assessments have broadened beyond multiple-choice
      question (MCQ) examinations and preceptor ratings. METHODS: A survey mailed to
      126 accredited U.S. medical schools asked respondents to indicate the frequency
      with which a variety of assessment methods were used in each year of the
      curriculum. RESULTS: Examinations dominated preclinical assessments. Year 3
      relied heavily on faculty ratings, live observations, and MCQs. Preceptor ratings
      were used most in year 4. CONCLUSIONS: A variety of competency assessments
      currently are used; MCQs remain a core assessment method. Year 3 had the greatest
      breadth of assessment strategies. The findings suggest that educators continue to
      be challenged to balance the breadth of competencies sampled with the fidelity of
      the assessment experience.

PMID- 11302035
TI  - Developing a training program to improve supervisor-resident relationships, step
      1: defining the types of issues.
AB  - BACKGROUND: By some estimates, the teacher-learner relationship explains roughly
      half of the variance attributed to the effectiveness of teaching. Despite this,
      relationships largely have been ignored in the educational literature. PURPOSE:
      This qualitative pilot study sought to identify factors in the supervisor
      resident relationship that hinder learning among University of Toronto psychiatry
      residents. METHOD: Thirteen postgraduate-year residents in Years 2-5 and their
      supervisors were interviewed regarding interactions that either assisted or
      adversely affected learning. RESULTS: Qualitative analysis of the interview data
      led to the identification of 5 types of issues affecting the supervisory
      relationship: goals and individual differences, communication and feedback, power
      and rivalry, support and collegiality, and role modeling and expertise. Face
      validity was supported when typed anonymous written feedback obtained from annual
      supervisor evaluations also could be organized into the 5 categories.
      CONCLUSIONS: Recognition of the types of interpersonal interactions that assist
      or hinder learning may contribute to enhanced teaching effectiveness.

PMID- 11302036
TI  - Do underrepresented minority medical students differ from non-minority students
      in problem-solving ability?
AB  - BACKGROUND: In medical education, examinations must assess a logical progression
      toward problem-solving skills. Differences in cognitive development between
      underrepresented minority students (URMs) and non-URMs may affect examination
      performance and subsequent attrition rates. PURPOSE: The authors investigated URM
      and non-URM performances by retrospectively analyzing success rates on exam items
      of differing cognitive demand. METHOD: Mean correct responses to exam items
      classified as Recall, Interpretation, or Problem-Solving questions were
      calculated. Both URM and non-URM groups were stratified by grade point average
      (GPA) and scores on the Medical College Admission Test (MCAT). Differences were
      investigated with analysis of variance and general linear models. RESULTS: For
      all students, performance levels decreased as the cognitive demands of the exam
      items increased. When stratified by GPA and MCAT score, several important
      differences were found between URM and non-URM performance. CONCLUSIONS: Because
      cognitive measures fail to account for the majority of performance differences,
      noncognitive attributes must contribute to the poorer performance of URMs.

PMID- 11302037
TI  - Screen-based anesthesia simulation with debriefing improves performance in a
      mannequin-based anesthesia simulator.
AB  - BACKGROUND: Previous investigations have established the need for improved
      training for management of anesthetic emergencies. Training with inexpensive
      screen-based anesthesia simulators may prove to be helpful. PURPOSES: We measured
      the effectiveness of screen-based simulator training with debriefing on the
      response to simulated anesthetic critical incidents. METHODS: Thirty-one 1st-year
      clinical anesthesia residents were randomized into 2 groups. The intervention
      group handled 10 anesthetic emergencies using the screen-based anesthesia
      simulator program and received written feedback on their management, whereas the
      traditional (control) group was asked to study a handout covering the same 10
      emergencies. All residents then were evaluated on their management of 4
      standardized scenarios in a mannequin-based simulator using a quantitative
      scoring system. RESULTS: The average point score for the simulator-with
      debriefing group was 52.6 +/- 9.9 out of 95 possible points. The traditional
      group average point score was 43.4 +/- 5.9, p = .004. CONCLUSIONS: Residents who
      managed anesthetic problems using a screen-based anesthesia simulator handled the
      emergencies in a mannequin-based anesthesia simulator better than residents who
      were asked to study a handout covering the same problems. Computer simulations
      with feedback are effective as a supplement to traditional residency training
      methods for the management of medical emergencies.

PMID- 11302038
TI  - Conversations with parents of medically ill children: a study of interactions
      between medical students and parents and pediatric residents and parents in the
      clinical setting.
AB  - BACKGROUND: The traditional remedies applied by medical schools to the perennial
      problem of teaching "caring competence" have been unsuccessful. PURPOSE: Our
      purpose was to design and evaluate a simple and effective method for helping
      students maintain affective contact with their patients. METHODS: Third-year
      medical students and pediatric residents were given the opportunity to talk
      informally with parents of medically ill children and reflect on the value of
      this experience for their learning. Trainees' opinions of the experience were
      measured with focus groups and a questionnaire. RESULTS: Trainees were delighted
      with the experience, particularly with the following aspects: the opportunity to
      hear a personally relevant story told in a sincere manner, the realization that
      they could have an authentic interaction "even" in a medical setting, and the
      usefulness of the information they derived from the conversation. CONCLUSIONS: We
      concluded that something unique to the conversational experience has educational
      value.

PMID- 11302039
TI  - Deepening the dialogue with our members.

PMID- 11302040
TI  - Looking back, looking forward with AIDS experts.

PMID- 11302041
TI  - The corrections revolution and HIV care.

PMID- 11302042
TI  - Ducking the crossfire of cross-resistance (Glasgow. Part 1).

PMID- 11302043
TI  - Searching the kingdom for a new weapon against HIV. Interview by Bob Roehr.

PMID- 11302044
TI  - Tax savings opportunities for physicians.

PMID- 11302045
TI  - Tips to keep litigation from knocking at your door.

PMID- 11302046
TI  - A new shade of blue. The relationship between Blue Cross and physicians takes on
      a new hue.

PMID- 11302047
TI  - Reimbursement stuck in the system? MSMS cuts red tape.

PMID- 11302048
TI  - Handheld computers making the rounds with physicians. Devices put medical know
      how-literally--in the palm of your hand.

PMID- 11302051
TI  - Are you enjoying your practice and your life?

PMID- 11302053
TI  - An ounce of prevention.

PMID- 11302052
TI  - Malpractice insurance: consent to settle and entity coverage.

PMID- 11302054
TI  - Surviving the survey process ... or hiding behind it?

PMID- 11302055
TI  - Food for thought. Preventing/treating malnutrition and dehydration.

PMID- 11302056
TI  - Creativity on a budget.

PMID- 11302057
TI  - They all fall down.

PMID- 11302058
TI  - New QC research refutes some common notions.

PMID- 11302059
TI  - Order-taker or marketeer?

PMID- 11302060
TI  - ASPs: do the math.

PMID- 11302061
TI  - HIMSS, hers and IT.

PMID- 11302062
TI  - Radiology report production times: voice recognition vs. transcription.
AB  - Computer-based voice-recognition software has many potential advantages in
      producing reports of radiology procedures. Using voice-recognition systems,
      however, necessitates increased involvement of the radiologist in the process of
      producing the report. The radiologist, previously responsible only for recording
      a report onto tape and ensuring the integrity of the final report now becomes
      obligated to interact with the computer and to ensure the integrity of the
      transcription process as well as the accuracy of the final report. Two attending
      radiologists and one first-year radiology resident at an academic medical center
      timed the production of reports using both the voice recognition system and tape
      transcription of reports of plain films (n = 27), mammograms (n = 25), and GI/GU
      exams (n = 17). In addition, the taped dictations were transcribed and then
      corrected by the physicians. The additional correction time (determined as an
      average) was added to the tape times to produce a "corrected" tape time. Paired T
      Test procedures were used to determine if pairs of readings (voice recognition
      vs. corrected tape transcription) differed in length of time. In addition, the
      data was stratified into three groupings--plain film, mammography, and GI/GU--in
      order to assess for differences between modalities. The length of time required
      to produce a radiology report using the commercial radiology voice recognition
      system employed at our center is significantly longer than that required by the
      traditional corrected tape transcription system. One motivation to use a voice
      recognition system is the cost savings achieved by eliminating transcriptionists
      and replacing them with the radiologist using the voice recognition system. In
      our institution this cost savings is estimated to be $100,000 annually. This
      apparent cost savings is reduced by the cost of the lost productivity of the
      radiologist. Compared to tape transcription, our data demonstrate a significant
      increase in the amount of time necessary for radiologists to produce a radiology
      report when using the voice recognition system currently employed in our
      hospital. While it is likely that future systems will require less extra time,
      this factor needs to be accounted for when departments consider using such
      systems to replace transcriptionists with radiologists.

PMID- 11302064
TI  - HIPAA--a real world perspective.
AB  - An effective and realistic approach to HIPAA compliance requires healthcare
      organizations to achieve a fundamental shift in attitude, awareness, habits and
      capabilities in the areas of privacy and security. They must create a sense of
      accountability among staff, and even patients, for the safeguarding of patient
      information. Only when this culture shift has occurred, along with the required
      technological advancements, can HIPAA compliance be realistically achieved. There
      is still ample time to create the organizational shift necessary, along with
      technological enhancements, to meet HIPAA requirements. Beyond compliance, HIPAA
      will benefit the healthcare industry by promoting administrative simplification-
      the original intention of the Act. And it will require the healthcare industry,
      in an abbreviated timeframe, to upgrade its level of sophistication in managing
      information. HIPAA certification springs from an organizational compliance method
      that has been underway in government for the past two decades. The HIPAA playbook
      is taken lock, stock and barrel from other Federal guidelines. HIPAA's
      legislative lineage includes the Healthcare Reform Act of 1993, Paperwork
      Reduction Act of 1980, Computer Security Act of 1987 and the Privacy Act of 1974.
      HIPAA means that public and private sector healthcare organizations are going to
      be required by law to adopt the same information-handling practices that have
      been in effect in the Federal government for years. That boils down to two
      things: Standardized formatting of data electronically exchanged between
      providers, payers and business partners (EDI) Federalization of security and
      privacy practices within private-sector healthcare information management The key
      to making HIPAA compliance achievable within a practical timeframe, as well as
      instituting the culture changes that go with enhanced privacy and security
      standards, is a process that is largely unfamiliar in the private sector, called
      administrative certification and accreditation. Certification is an
      organizational change-management methodology that drives accountability for
      security down to that level in the organization where it will concretely and
      tangibly get done. It is a comprehensive managerial assessment of the technical
      and non-technical security features and other safeguards of a system associated
      with its use and environment. The assessment seeks to establish and document the
      extent to which a particular system meets a set of specified security
      requirements. HIPAA accreditation occurs when all functional managers in an
      organization have completed reports of what they know they need to do in their
      areas. They submit that information to an executive official within the
      organization who functions as the accrediting official for the organization.
      Accreditation is the formal declaration that an information system is approved to
      operate in a particular security mode using a prescribed set of safeguards and
      should be strongly based on the solvable vulnerabilities and residual risks
      identified during certification. Institutionalizing a practical and formal HIPAA
      certification program is important to support business activities and can provide
      several benefits including increased communication within an organization.

PMID- 11302063
TI  - An ancient fable and a future fable.

PMID- 11302065
TI  - Defining DICOM (Digital Imaging and Communications in Medicine) requirements.

PMID- 11302066
TI  - Embracing cultural diversity.
AB  - Healthcare providers from all backgrounds are taught the Western medicine
      approach with little consideration given to cultural-specific care. Yet, today it
      is difficult to ignore that approximately 33 percent of Americans originate from
      ethnically diverse groups. As our population continues to become more
      diversified, it is imperative that healthcare professionals become more sensitive
      to cultural differences. Effectively managing cultural diversity in the workplace
      requires a complex set of skills as well as an understanding of the concept.
      Communication skills will be challenged in a complex and diverse work
      environment. Managers must learn to listen. Embracing cultural diversity is a two
      step process. The first step begins with personal self-interest and self
      examination. The second step in the process is the "awakening." Tomorrow's
      successful managers will take an active role today in creating an environment
      that views diversity as an asset to the work force.

PMID- 11302067
TI  - CT technology overview.
AB  - I hope that you will find the product matrix to be a useful tool for making
      comparisons between vendors and scanners. Please keep in mind that the vendors
      have directly provided the specific answers to the questions within the matrix.
      Neither the author nor Radiology Management shall be held responsible for any
      misrepresented or erroneous data.

PMID- 11302068
TI  - A capital enigma.

PMID- 11302070
TI  - Using music therapy to help a client with Alzheimer's disease adapt to long-term
      care.
AB  - The purpose of this case study is to illustrate how music therapy can be used to
      help the elderly successfully adjust to living in a long-term care (LTC)
      facility. LTC residents, particularly those with Alzheimer's disease or related
      dementia, may exhibit behaviors such as depression, withdrawal, anxiety,
      emotional liability, confusion, and memory difficulties, frequently related to
      the disorder, but often exacerbated by difficulty in adjustment to the change in
      lifestyle. The subject of this case study demonstrated these symptoms. Music
      therapy helped him adjust to life in a LTC setting by improving his quality of
      life and enhancing his relationships with those around him. As chronicled in this
      study, music therapy may facilitate a resident's adjustment to life in a LTC
      facility. N.B. Names and identifying information have been changed to protect
      privacy.

PMID- 11302071
TI  - Early stage dementia group: an innovative model of support for individuals in the
      early stages of dementia.
AB  - Traditionally, supports and services for people diagnosed with Alzheimer's
      disease have focused on the caregivers. The increase in early diagnosis of
      Alzheimer's disease has resulted in greater numbers of older adults that have
      some insight and awareness of their deficits and are capable of dealing with the
      ramifications of their illness. Yet there are few places to turn for support and
      education. Circle of Care, a community-based home support agency in Toronto, has
      developed a support group for individuals with early stage dementia.
      Comprehensive Rehabilitation and Mental Health Services (COTA), a community-based
      rehabilitation agency, was invited to provide a co-facilitator for this group. To
      date, three groups have been held, each one having a fixed membership and meeting
      for eight sessions of one and a quarter hours. Topics focused on causation,
      coping with memory problems, loss, grief, and daily living skills. Positive
      themes emerged to reveal feelings of affirmation, camaraderie, and improved
      confidence, while feelings of helplessness and frustration were also raised.
      Implications for future planning and interventions also will be discussed in this
      paper.

PMID- 11302072
TI  - Bingo vs. physical intervention in stimulating short-term cognition in
      Alzheimer's disease patients.
AB  - Past research has shown that pharmacological measures can enhance cognitive and
      functional capacities for patients with Alzheimer's disease, but may result in
      unacceptable side effects. Investigations using nonpharmacological treatments are
      limited. This study evaluates the therapeutic effect of the game of Bingo as
      cognitive stimulation, versus daily physical activity, on short-term memory,
      concentration, word retrieval, and word recognition. Informed consent was
      obtained from the designated representatives of 50 subjects from six community
      adult day care centers on Long Island. The results show that cognitive
      stimulation enhanced performance on the Boston Naming Test and a Word List
      Recognition Task; physical intervention, however, did not reach statistical
      significance. Thus, a simple cognitive activity such as Bingo can be of great
      value to the daily management of Alzheimer's patients.

PMID- 11302073
TI  - Roommate-pairing: a nonpharmacologic therapy for treating depression in early to
      mid stages of Alzheimer's disease and dementia.

PMID- 11302074
TI  - Apolipoprotein-E gene polymorphism and lipid profiles in Alzheimer's disease.
AB  - In this study, the relationship between lipid profiles of sera and apolipoprotein
      E (apo E) gene polymorphism was investigated in 35 patients with Alzheimer's
      disease (AD) and 29 healthy people. Apo E genotypes and allele frequencies of the
      AD patient group were: apo E2/3, 2 (5.7 percent); apo E2/4, 1 (2.9 percent); apo
      E3/3, 26 (74.3 percent); apo E3/4, 5 (14.3 percent); apo E4/4, 1 (2.9 percent);
      epsilon 2, 3(4.2 percent); epsilon 3, 59 (84.2 percent); epsilon 4, 8 (11.4
      percent). The healthy group's apo E genotypes and allele frequencies were: apo
      E2/3, 1 (3.4 percent); apo E3/3, 27 (93.1 percent); apo E3/4, 1 (3.4 percent);
      epsilon 2, 1 (1.7 percent); epsilon 3, 56 (96.5 percent); epsilon 4, 1 (1.7
      percent). In Alzheimer's cases, epsilon 4 allele frequencies increased
      significantly as compared to the healthy group (p < 0.05). When the effects of
      the apo E isoforms on lipid profiles were evaluated, a relationship between apo E
      epsilon 4 allele and high total levels of serum cholesterol was found, whereas of
      apo E epsilon 2 allele was associated with the low total cholesterol of serum,
      although the difference was not statistically significant (p > 0.05). This study
      confirms the association of apo E epsilon 4 allele with lipid profiles in AD
      patients.

PMID- 11302075
TI  - Inherited Alzheimer's disease PS-1 olfactory function: a 10-year follow-up study.
AB  - This study was undertaken to evaluate smell tests as a clinical marker for
      identifying mutation carrier status and determining the clinical diagnosis of
      presenilin-1 Alzheimer's disease (AD) in family members of those afflicted with
      the disease. Ten years ago, we gave the self-administered, 40-question scratch
      and sniff University of Pennsylvania Smell Identification Test to 18 at-risk
      family members, individuals with dominantly-inherited Alzheimer's disease.
      Testing results were normal 10 years ago except in the case of one individual who
      had smoked three packs of cigarettes a day for more than 23 years. Four subjects
      tested in 1990 are now afflicted with Alzheimer's disease, including the smoker.
      The smell test in 1990 did not demonstrate predictive capabilities before
      clinical conversion to dementia. At follow-up, two subjects were too impaired to
      take the test. Two "converted" from normal smell function to abnormal function
      with a wide range in score. Study findings indicate that the smell test is too
      variable a measure to be used as a reliable test for predicting or verifying a
      diagnosis of presenilin-1 Alzheimer's disease.

PMID- 11302076
TI  - Empowering individuals with early dementia and their carers: an exploratory study
      in the Chinese context.
AB  - This article discusses an early dementia program developed for sufferers and
      family carers in a Chinese context. Instead of replicating formats of similar
      programs developed in Western countries, this program considered cultural issues
      and caring values that are unique to Chinese people. Its main objective was to
      empower sufferers and carers through educational activities and support programs.
      Observations and interviews were used for program evaluation. The program creates
      a "win-win" situation in which both parties experienced pleasurable feelings and
      developed a close relationship. It also highlights the values of "meaningful
      occupation" in dementia care. Furthermore, the program broadens our understanding
      of needs and concerns of sufferers and carers at early stages, which are deemed
      important to develop continuous dementia programs along the disease course.

PMID- 11302077
TI  - Legal guardianship and other alternatives in the care of elders with Alzheimer's
      disease.
AB  - This paper discusses planned instructional and proxy interventions for
      incapacity, legal guardianship, and supplements to care for people with
      Alzheimer's disease (AD). Service providers are encouraged to identify and
      initiate care decisions that are consistent with the client's care preferences.
      Case examples are discussed. Practitioners are encouraged to educate clients,
      particularly those in the early stages of Alzheimer's disease, to create evidence
      for care preferences through planning. Service providers' concerns for liability
      are briefly discussed.

PMID- 11302078
TI  - Comparing the well-being of post-caregivers and noncaregivers.
AB  - Researchers who study family caregiving have begun to recognize the need to
      broaden the realm of inquiry to include the exploration of the positive aspects
      of caregiving as well as conceptualizing caregiving on a continuum from the pre
      caregiving phase through the post-caregiving phase. Additionally, researchers are
      urged to use control groups in research. This study complements the current
      trends by examining the positive aspects of caregiving among former caregivers.
      Specifically, the well-being of post-caregivers is compared to that of
      noncaregivers. Bivariate analyses examine the factors that are significantly
      different between former caregivers and noncaregivers. Results show that former
      caregivers have higher well-being than noncaregivers. In the multivariate model,
      only one subscale of well-being (basic needs) is different between the two
      groups. Implications of this research are discussed.

PMID- 11302079
TI  - [Angina tonsillaris in children. Penicillin V can not be recommended here].

PMID- 11302080
TI  - [BgVV warns about certain vitamin preparations. Betacarotene: useless and even
      harmful (interview by W. Paukstadt)].

PMID- 11302081
TI  - [Managing oncological patients. It can also be done on an ambulatory basis].
AB  - A consequence of an increasing tendency to manage oncological patients on an
      outpatient basis is that, apart from the care-providing oncologist, family
      doctors are also being involved. Only with the aid of adequate supportive
      measures is it possible to ensure treatment of such patients with the more
      intensive forms of therapy as chemotherapy or combined radiochemotherapy within
      their social environment. In addition to enteral and parenteral nutrition adapted
      to individual requirements, differentiated pain control is of major importance.
      Side effects of chemotherapy or radiotherapy often necessitate rapid
      intervention, and thus also short communication pathways between family doctor
      and oncologist. Joint efforts are also necessary when helping the patient cope
      with his/her disease.

PMID- 11302082
TI  - [Patient treated with chemotherapy. Alarm signs requiring immediate
      intervention].
AB  - The most common complications in patients receiving chemotherapy are neutropenia
      with fever, and infections. The risk-adapted application of antibodies,
      antimycotics and G-CSF is discussed. Nausea and vomiting can usually be avoided
      by appropriate prophylactic antiemetic treatments. Less common are
      thrombocytopenia requiring replacement treatment. The frequent anemias associated
      with tumor treatment have a multifactorial genesis. Red cell concentrates and,
      where indicated, erythropoietin are available. Typical organ-related side effects
      of cytostatic agents are rare, but then usually serious. Problems with veins may
      be resolved with "undertunneled" central venous catheters or completely implanted
      port systems.

PMID- 11302084
TI  - [Model project for managing terminally ill cancer patients. Dying at home--this
      wish can often be fulfilled].

PMID- 11302083
TI  - [Depression in cancer patients. Early recognition--adequate treatment].
AB  - During or following chemotherapy, cancer patients frequently suffer from
      depression, asthenia and lassitude, which may have an unfavorable effect on the
      course of the disease. Psychotherapeutic interventions and psychopharmaceuticals
      can significantly ameliorate these symptoms and thus improve the patient's
      quality of life. Over the long term, the general practitioner has a key
      diagnostic and therapeutic function. While monitoring the further course of the
      patient, he can recognize the signs of depression and call in specialist help.

PMID- 11302085
TI  - [Emergencies in general practice, 7. Epistaxis--diagnosis and therapy].

PMID- 11302086
TI  - [Diabetic foot syndrome. Charcot foot].

PMID- 11302087
TI  - [Travel medicine consultation with the family physician: so that your patients
      return healthy!].

PMID- 11302088
TI  - [Diagnostic quiz. Pulmonary coin lesion in a young man. Lung abscess in HIV
      infection].

PMID- 11302089
TI  - Ethics and Internet healthcare: an ontological reflection.

PMID- 11302090
TI  - Home-based telemedicine: a survey of ethical issues.

PMID- 11302091
TI  - Patient access to medical information in the computer age: ethical concerns and
      issues.

PMID- 11302092
TI  - The Internet, confidentiality, and the pharmacy.coms.

PMID- 11302093
TI  - Ethical perspectives in evaluation of telehealth.

PMID- 11302094
TI  - CQ sources/bibliography. Cyberethics: the Internet and allied technologies.

PMID- 11302095
TI  - Employer leadership in the era of workplace rationing.

PMID- 11302096
TI  - Autonomy, benevolence, and Alzheimer's disease.

PMID- 11302097
TI  - May a woman clone herself?

PMID- 11302098
TI  - But what if we feel that cloning is wrong?

PMID- 11302099
TI  - Care planning for individuals with chronic mental illness and/or substance abuse
      problems: policy implementation for community mental health centers.

PMID- 11302100
TI  - [Principles of management of All-Russia Disaster Medicine Services].
AB  - Experience of liquidation of earthquake consequences in Armenia (1988) has shown
      that it is extremely necessary to create the system of management in regions of
      natural disaster, large accident or catastrophe before arrival of main forces in
      order to provide reconnaissance, to receive the arriving units. It will help to
      make well-grounded decisions, to set tasks in time, to organize and conduct
      emergency-and-rescue works. The article contains general material concerning the
      structure of All-Russia service of disaster medicine (ARSDM), organization of
      management at all levels and interaction between the components of ARSDM and
      other subsystems of Russian Service of Extreme Situations. It is recommended how
      to organize management of ARSDM during liquidation of medical-and-sanitary
      consequences of large-scale extreme situations.

PMID- 11302101
TI  - [Telomerase--new diagnostic and therapeutic options in oncology].
AB  - One of the new directions in study of malignant tumor pathogenesis is telomerase
      theory. Investigations in the culture of human cells have shown that telomerase
      activation can lead to tumor development. Prospective investigations of
      telomerase could be able to supplement the data about tumor pathomorphology and
      will permit to conduct monitoring on patients with malignant tumors by studying
      telomerase in fractionated cells from different body tissues and biological
      media. Telomerase inhibitors are possible drugs for antitumoral therapy. It is
      supposed that the abovementioned agents will decrease telomerase activity of
      proliferating tumoral cells that will cause destabilization of their genome,
      stopping of proliferation and death of tumoral clone.

PMID- 11302102
TI  - [Experience of the surgical department of the therapeutic and diagnostic center].

PMID- 11302103
TI  - [Combined therapy with nitrosorbide and preductal in patients with ischemic heart
      disease].

PMID- 11302105
TI  - [Significance of inflammatory diseases of otorhinolaryngological organs in
      etiology and pathogenesis of myopia in the Air Forces flying personnel].
AB  - Complex ophthalmologic examination (visorefracto- and accommodometry) and study
      of disease structure were conducted in 1189 persons of flying staff. In the main
      group (persons with myopia) LOR-diseases were noticed 3.6 times more often than
      in those without myopia. In pilots with myopic refraction chronic inflammatory
      diseases of palatine tonsils: chronic compensated (35.5%) and decompensated (27%)
      tonsillitis occur 7-12 times more often than in control group. Investigation of
      visual function has revealed that in the group of persons without the history of
      chronic tonsillitis the least degree of myopia, the greatest visual acuity
      without correction, the least value of progress gradient and minimal decrease in
      indices of relative and absolute accommodation were observed. In persons after
      tonsillectomy the mentioned parameters of visual functions are close to the
      values obtained in pilots without the history of chronic tonsillitis; only
      accommodative functions were practically twice decreased. Chronic tonsillitis
      causes the greater degree of myopia and gradient of its progress and respectively
      more lower visual acuity and significant decrease in accommodation indices (P <
      0.05). Also it has been detected that if myopia was diagnosed in a year or more
      after tonsillectomy then myopia and degree of visual function disorders
      respectively were minimal. If the operation was performed in a year or more after
      myopia detection the disorders in visual functions were more expressed and myopia
      reached significantly higher values (P < 0.05).

PMID- 11302104
TI  - [Antiviral efficacy of the cream Geophor (preclinical study)].

PMID- 11302106
TI  - [Medical and juridical aspects of the international humanitarian law (on the
      190th birthday of N. I. Pirogov)].

PMID- 11302107
TI  - [Participation of medical services of the Armed Forces in activities of the
      International Committee of Military Medicine and Pharmacies].

PMID- 11302108
TI  - [The military hospital at the cosmic harbor].

PMID- 11302109
TI  - Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271
      patients with recent myocardial infarction: do stopped trials contribute to
      overall knowledge? GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio
      della Sopravvivenza nell'Infarto Miocardico).
AB  - BACKGROUND: The aim of this study was to test the efficacy of a low-dose
      pravastatin regimen (20 mg daily) in patients with myocardial infarction.
      METHODS: GISSI Prevenzione (GISSI-P) is an open trial on secondary coronary heart
      disease prevention: 4271 recent acute myocardial infarction patients (< or = 6
      months) with total blood cholesterol > or = 200 mg/dl were randomized to low-dose
      cholesterol-lowering treatment (pravastatin 20 mg daily) or no treatment. GISSI-P
      was started in 1993 and its story was crossed by the publication of the results
      of similarly designed clinical trials. The publication of 4S results in 1994
      prompted the Data Safety and Monitoring Board (DSMB) and the Steering Committee
      (SC) to change the protocol so that only patients whose total blood cholesterol
      was < 250 mg/dl could be randomized whilst patients with total blood cholesterol
      > 250 mg/dl who had already been enrolled in the study had to be re-evaluated
      and, if appropriate, pharmacologically treated. The DSMB and the SC agreed to
      stop randomization prematurely in late 1996 after the publication of CARE
      results. RESULTS: Mean follow-up time was 23.0 +/- 6.7 months (median 24.3
      months). The two treatment groups were well matched at baseline. Pharmacological
      interventions recommended by the protocol were widely prescribed (antiplatelet
      agents > 90%, beta-blockers 42.7%, and ACE-inhibitors 40.2%). Mainly because of
      the on-course modification of the study protocol, 402/2133 (18.8%) patients in
      the control group started a cholesterol-lowering treatment during follow-up.
      Conversely, 296/2138 (13.8%) patients permanently stopped taking their tablets.
      Side effects, however, were the reason for discontinuing therapy in 57 (2.7%)
      patients in the pravastatin group, and patient reluctance to continue accounted
      for most of the remainder. After excluding control patients who had started a
      cholesterol-lowering treatment during follow-up, the following changes of median
      lipid concentrations in the control group over the whole course were observed:
      total cholesterol -1.9%; LDL cholesterol -2.9%; triglycerides -2.0%; HDL
      cholesterol +1.4%. The analysis carried out excluding patients randomized to
      pravastatin treatment and actually not assuming the drug clearly indicated the
      cholesterol-lowering efficacy of low-dose pravastatin (total cholesterol -12.5%;
      LDL cholesterol -18.8%; triglycerides -7.9%; HDL cholesterol +3.4%). During the
      study 256 (6.0%) patients either died or had a non-fatal stroke or a myocardial
      infarction, 136 (6.4%) in the control group and 120 (5.6%) in the pravastatin
      group (relative risk 0.90, 95% confidence interval 0.71-1.15, p = 0.41); 160
      patients died, 88 (4.1%) in the control group and 72 (3.4%) in the pravastatin
      group (relative risk 0.84, 94% confidence interval 0.61-1.14, p = 0.26). The few
      (n = 28) non-cardiovascular deaths were balanced: 16 (0.8%) in the control group
      and 15 (0.6%) in the pravastatin group. The reduction of cardiovascular events
      was more evident in the by-treatment analysis, with coronary heart disease deaths
      being significantly decreased (relative risk 0.60, 95% confidence interval 0.38
      0.96, p = 0.04). The overall frequency of adverse events was similar in the two
      groups. No significant difference between treatment groups was found for total
      cases of cancer or at any particular site. CONCLUSIONS: Despite the decreased
      statistical power due to its premature stopping, the results of the GISSI-P
      suggest that a low-dose treatment with pravastatin (20 mg daily) is effective in
      reducing blood lipids, and underline the importance of long-term compliance with
      treatments in the search for a maximal effective dosage. Furthermore, the effects
      of a statin on total and coronary mortality quantified for the first time in a
      population exposed to Mediterranean dietary and lifestyle habits are markedly
      consistent with those obtained in different settings.

PMID- 11302110
TI  - Epidemiologic evidence on the carcinogenicity of silica: factors in scientific
      judgement.

PMID- 11302111
TI  - Identification and quantification of caffeic and rosmarinic acid in complex plant
      extracts by the use of variable-temperature two-dimensional nuclear magnetic
      resonance spectroscopy.
AB  - A combination of advanced nuclear magnetic resonance (NMR) methodologies for the
      analysis of complex phenolic mixtures that occur in natural products is
      described, with particular emphasis on caffeic acid and its ester derivative,
      rosmarinic acid. The combination of variable-temperature two-dimensional proton
      proton double quantum filter correlation spectroscopy (1H-1H DQF COSY) and proton
      carbon heteronuclear multiple quantum coherence (1H-13C HMQC) gradient NMR
      spectroscopy allows the identification and tentative quantification of caffeic
      and rosmarinic acids at 243 K in extracts from plants of the Lamiaceae family,
      without resorting to previous chromatographic separation of the components. The
      use of proton-carbon heteronuclear multiple bond correlation (1H-13C HMBC)
      gradient NMR spectroscopy leads to the complete assignment of the correlations of
      the spins of H2a and H3a with the ester and carboxyl carbons of rosmarinic and
      caffeic acid, even at room temperature, and confirms the results of the above
      methodology Quantitative results are in reasonable agreement with reverse phase
      HPLC measurements.

PMID- 11302112
TI  - NMR evidence for benzodioxane structures resulting from incorporation of 5
      hydroxyconiferyl alcohol into Lignins of O-methyltransferase-deficient poplars.
AB  - Benzodioxane structures are produced in lignins of transgenic poplar plants
      deficient in COMT, anO-methyltransferase required to produce lignin syringyl
      units. They result from incorporation of 5-hydroxyconiferyl alcohol into the
      monomer supply and confirm that phenols other than the three traditional
      monolignols can be integrated into plant lignins.

PMID- 11302113
TI  - Target-controlled alfentanil analgesia for dressing change following extensive
      reconstructive surgery for trauma.

PMID- 11302114
TI  - Opioids for severe pain: little change over 15 years.

PMID- 11302115
TI  - Na(+)-dependent electrogenic ATPase from the plasma membrane of the halotolerant
      microalga Dunaliella maritima.

PMID- 11302116
TI  - The Ross procedure: Is it the ideal operation for the young with aortic valve
      disease?
AB  - BACKGROUND: Aortic valve prosthesis with adequate hemodynamic performance should
      allow more complete left ventricular mass regression and normalize left
      ventricular function. This possibly affects long-term prognosis after aortic
      valve replacement. OBJECTIVE: Assessment of hemodynamic performance of pulmonary
      autograft in the aortic position and the regression of left ventricular mass
      after the Ross procedure. METHODS: Between May 1995 and March 1996, 45 patients
      with mean age of 27.1 years underwent a Ross procedure. Doppler echocardiography
      and cardiac catheterization were performed on all patients before hospital
      discharge to evaluate the hemodynamic performance of auto- and homografts, as
      well as to evaluate left ventricular mass and function. Fourteen patients with
      follow-up longer than six months were submitted to dobutamine stress
      echocardiography to study the hemodynamic performance of auto- and homografts
      during exercise. RESULTS: Hospital mortality was 6%. After a mean follow-up of
      12.8 months (1-23 months) there was one late sudden death. No valve-related event
      was observed during this period. Immediate and late hemodynamic performance of
      the pulmonary autografts were normal with an average mean gradient of 1.8 +/- 0.6
      mmHg and an average maximum instantaneous gradient of 2.9 +/- 0.9 mmHg. Valvular
      insufficiency was insignificant. Even during exercise, gradients did not increase
      significantly with an average mean gradient of 4.3 +/- 2.5 mmHg and an average
      maximum gradient of 10.4 +/- 6.1 mmHg. Homografts used for right ventricular
      reconstruction showed excellent immediate hemodynamic performance. However, at
      late follow-up an increase in flow speed was observed with an average to mean
      gradient of 10 +/- 7.1 mmHg at rest and 26 +/- 13.2 mmHg during exercise. Left
      ventricular mass index was normal at rest and during exercise in the majority of
      patients. CONCLUSION: Given the normal hemodynamic function of pulmonary
      autografts, the reduction of ventricular mass and normalization of left
      ventricular function, in addition to the excellent late follow-up of the
      patients, the Ross procedure is considered the operation of choice for young
      patients requiring aortic valve replacement.

PMID- 11302117
TI  - A report of the treatment of coronary artery aneurysm without cardiopulmonary
      bypass.
AB  - Coronary artery aneurysm (CAA) is a fairly rare pathologic entity whose exact
      incidence is unknown but has been reported from 1.4% in autopsy series [Daoud,
      1963] to 4.9% in the Coronary Artery Surgery Registry [Swaye, 1984]. While
      atherosclerosis is the most common cause of true coronary artery aneurysms,
      pseudoaneurysms most often occur as complications of percutaneous transluminal
      coronary angioplasty (PTCA) or directional artherectomy [Dralle, 1995]. We report
      the successful treatment of a coronary artery aneurysm with comcomitant coronary
      revascularization without the use of cardiopulmonary bypass in a patient with
      impaired pulmonary and myocardial function. The use of an intracoronary shunt,
      previously described by one of the authors (EW), facilitated the surgical
      procedure [Franzone 1977].

PMID- 11302118
TI  - Physician recognition of active drug use in HIV-infected patients is lower than
      validity of patient's self-reported drug use.
AB  - A French survey of 325 HIV-infected subjects with a history of injecting drugs
      allowed us to study the recognition of patients' injection drug use (IDU) by
      physicians providing HIV-infection care, and to analyze the correlation between
      patient demographics and incorrect IDU identification. Kappa for concordance of
      physician's reports of their patient's IDU with patient's declaration was 0.37;
      concordance was lower among socially vulnerable patients. This contrasted with a
      nested study of validity of patient's self-report of opioid use: Kappa for
      patient's declaration of opioid use within the past two days against a biological
      assay was 0.61, and concordance was higher among socially vulnerable patients.
      Concordance of physicians' ratings and patients' reports of IDU was not more than
      fair, even though physicians were knowledgeable about their patient's IDU
      history. This concordance varied with social status in a way that did not
      correspond with variations in self-reported opioid use validity, suggesting that
      identification of active IDU might be partly based on incorrect interpretation of
      subjective cues.

PMID- 11302119
TI  - More on the use of nonsteroidal anti-inflammatories in the management of cancer
      pain.

PMID- 11302120
TI  - Difficulties in pain control among injection drug users with necrotizing
      fasciitis.

PMID- 11302121
TI  - Prevention of chronic pain in whiplash injury.

PMID- 11302122
TI  - Differences in gabapentin efficacy for cancer pain more apparent than real?

PMID- 11302123
TI  - Interview with Richard K. Myler, MD by Laurie Gustafson.

PMID- 11302124
TI  - Diffuse large B-cell lymphoma with spindle cell features.

PMID- 11302125
TI  - The 'Terra Preta' phenomenon: a model for sustainable agriculture in the humid
      tropics.

PMID- 11302126
TI  - Birds of a feather.

PMID- 11302127
TI  - Sympathetic ophthalmia associated with high frequent deafness.

PMID- 11302128
TI  - Similarities in the packaging of cyanoacrylate nail glue and ophthalmic
      preparations: an ongoing problem.

PMID- 11302129
TI  - Disconjugate vertical ocular movement in a patient with locked-in syndrome.

PMID- 11302130
TI  - Conjunctival CD5+ MALT lymphoma.

PMID- 11302131
TI  - Autosomal dominant microcephaly--lymphoedema-chorioretinal dysplasia syndrome.

PMID- 11302132
TI  - Uveitis associated with OKT3 therapy for renal transplant rejection.

PMID- 11302133
TI  - Maxillary sinus non-Hodgkin's lymphoma with orbital and intraocular involvement
      in the acquired immunodeficiency syndrome.

PMID- 11302134
TI  - Pythium insidiosum keratitis confirmed by DNA sequence analysis.

PMID- 11302135
TI  - From the Centers for Disease Control and Prevention. Impact of the 1999 AAP/USPHS
      Joint Statement on Thimerosal in Vaccines on Infant Hepatitis B Vaccination
      Practices. American Academy of Pediatrics/U.S. Public Health Service.

PMID- 11302136
TI  - From the Centers for Disease Control and Prevention. Trends in screening for
      colorectal cancer--United States, 1997 and 1999.

PMID- 11302137
TI  - From the Centers for Disease Control and Prevention. Prevalence of disabilities
      and associated health conditions among adults--United States, 1999.

PMID- 11302138
TI  - JAMA patient page. Pregnancy complications.

PMID- 11302139
TI  - The doctor's letter of condolence.

PMID- 11302140
TI  - Fludarabine for chronic lymphocytic leukemia.

PMID- 11302141
TI  - Fludarabine for chronic lymphocytic leukemia.

PMID- 11302142
TI  - Fludarabine for chronic lymphocytic leukemia.

PMID- 11302143
TI  - Fludarabine for chronic lymphocytic leukemia.

PMID- 11302144
TI  - Familial aggregation of Parkinson's disease.

PMID- 11302145
TI  - Quality of care in the Veterans Health Administration.

PMID- 11302146
TI  - Quality of care in the Veterans Health Administration.

PMID- 11302147
TI  - Schistosoma haematobium.

PMID- 11302148
TI  - Schistosoma haematobium.

PMID- 11302149
TI  - Mother-to-child transmission of Burkholderia pseudomallei.

PMID- 11302150
TI  - Homozygous methylenetetrahydrofolate reductase C677T mutation and male
      infertility.

PMID- 11302151
TI  - From the Centers for Disease Control and Prevention. Update on the supply of
      tetanus and diphtheria toxoids and of diphtheria and tetanus toxoids and
      acellular pertussis vaccine.

PMID- 11302152
TI  - From the Centers for Disease Control and Prevention. Lyme disease--United States,
      1999.

PMID- 11302153
TI  - JAMA patient page. Autistic disorder.

PMID- 11302154
TI  - Improvement of desulfurization activity in Rhodococcus erythropolis KA2-5-1 by
      genetic engineering.
AB  - Rhodococcus erythropolis KA2-5-1 can desulfurize dibenzothiophene (DBT) into 2
      hydroxybiphenyl. A cryptic plasmid, pRC4, which was derived from R. rhodochrous
      IFO3338, was combined with an Escherichia coli vector to construct an E. coli
      Rhodococcus shuttle vector. The complete nucleotide sequence of 2582-bp pRC4 was
      analyzed. Based on the characteristics of its putative replication genes, pRC4
      was assigned to the family of pAL5000-related replicons. The desulfurization gene
      cluster, dszABC, and the related reductase gene, dszD, cloned from KA2-5-1, were
      reintroduced into KA2-5-1 and efficiently expressed. The DBT desulfurization
      ability of the transformant carrying two dszABC clusters and one dszD on the
      vector was about 4-fold higher than that of the parent strain, and the
      transformant also showed improved desulfurization activity for light gas oil
      (LGO). Sulfur components in LGO before and after the reaction were analyzed with
      gas chromatography-atomic emission detection.

PMID- 11302155
TI  - Isolation and characterization of enterocin SE-K4 produced by thermophilic
      enterococci, Enterococcus faecalis K-4.
AB  - Enterococcus sp. K-4, with a bacteriocin-like activity against E. faecium, was
      isolated from grass silage in Thailand. Morphological, physiological, and
      phylogenetic studies clearly identified strain K-4 as a strain of E. faecalis.
      Strain K-4 produced a maximal amount of bacteriocin at 43-45 degrees C. We
      purified, for the first time, the bacteriocin produced at high temperature by E.
      faecalis to homogeneity, using adsorption on cells of the producer strain and
      reversed-phase liquid chromatography. The bacteriocin, designated enterocin SE
      K4, is a peptide of about 5 kDa as measured by SDS-PAGE, and Mass spectrometry
      analysis found the molecular mass of 5356.2, which is in good agreement. The
      amino acid sequencing of the N-terminal end of enterocin SE-K4 showed apparent
      sequence similarity to class IIa bacteriocins. Enterocin SE-K4 was active against
      E. faecium, E. faecalis, Bacillus subtilis, Clostridium beijerinckii, and
      Listeria monocytogenes. Enterocin SE-K4 is very heat stable.

PMID- 11302156
TI  - New classification system for oxygenase components involved in ring-hydroxylating
      oxygenations.
AB  - Batie et al. [Chemistry and Biochemistry of Flavoenzymes, 3, 543-556 (1991)]
      proposed a classification system for ring-hydroxylating oxygenases in which the
      oxygenases are grouped into three classes in terms of the number of constituent
      components and the nature of the redox centers. But in recent years, many ring
      hydroxylating oxygenases have been newly identified and characterized, and found
      difficult to classify into these three classes. Typical examples are carbazole
      1,9a-dioxygenase and 2-oxo-1,2-dihydroquinoline 8-monooxygenase, which have been
      classified into class III and class IB, respectively, from biochemical
      characteristics. However, a phylogenetic study showed that the terminal
      oxygenases of both are closely related to class IA. Because this discrepancy
      derived from counting all the components together, here we proposed a new scheme
      based on the homology of the amino acid sequences of the alpha subunits of the
      terminal oxygenase components. This new scheme strongly reflects the actual
      phylogenetic affiliation of the terminal oxygenase component. By comparing their
      sequences pairwise using the CLUSTAL W program, 54 oxygenase components were
      classified into 4 groups (groups I, II, III, and IV). While group I contains
      broad-range oxygenases sharing low homology, groups II, III, and IV contain some
      typical oxygenases: benzoate/toluate dioxygenases for group II,
      naphthalene/polycyclic aromatic hydrocarbon dioxygenases for group III, and
      benzene/toluene/biphenyl dioxygenases for group IV. Our new scheme is simple and
      powerful, since an oxygenase component can be nearly automatically grouped when
      the DNA sequence is available, and it fits very well with the phylogenetic
      affiliation.

PMID- 11302157
TI  - Effect of dietary short-chain fructooligosaccharides on the cecal microflora in
      gastrectomized rats.
AB  - Total gastric resection is known to lead to changes in the microflora in the
      whole gastrointestinal tract. Dietary short-chain fructooligosaccharides (Sc-FOS)
      have been shown to also induce a change in the microflora in the large bowel by
      promoting an increase in the numbers of Bifidobacterium and Lactobacillus which
      have beneficial effects on the host. In the present study, 4-week-old male
      Sprague-Dawley rats received total gastrectomy or laparotomy, and each of these
      surgically treated groups was randomly divided into two experimental diet groups
      and given a 7.5% Sc-FOS diet or control diet. Enumeration and identification of
      the cecal bacteria was performed by using selective and non-selective media. In
      the gastrectomized rats, the total bacterial count, and the counts of
      Bacteroidaceae and Enterobacteriaceae were higher than those in the sham-operated
      rats. Sc-FOS promoted an increase in the numbers of Bifidobacterium and
      Lactobacillus, In the rats fed on the Sc-FOS diet, the predominant type of
      bacteria was Lactobacillus and in the rats fed on the control diet, it was
      Bacteroidaceae irrespective of gastrectomy. We confirmed that both gastrectomy
      and dietary Sc-FOS changed the composition of cecal microflora in the rats.
      Dietary Sc-FOS in the gastrectomized rats increased the proportions of
      Lactobacillus relative to other types of bacteria to levels similar to those seen
      in healthy normal rats, and decreased the proportion of Bacteroidaceae.

PMID- 11302158
TI  - Synthesis, absolute configuration and biological activity of both enantiomers of
      2-(5,6-dichloro-3-indolyl)propionic acid: new dichloroindole auxins.
AB  - Racemic 2-(5,6-dichloro-3-indolyl)propionic acid (5,6-Cl2-2-IPA) was synthesized
      from 5,6-dichloroindole-3-acetic acid (5,6-Cl2-IAA) by successive esterification,
      methoxycarbonylation, methylation, and double hydrolysis. The racemate was
      converted to the diastereomeric esters of (S)-(-)-1-phenylethyl alcohol. These
      were separated by HPLC into two optically active diastereomers and then
      hydrolyzed with p-TsOH to the optically active enantiomers of 5,6-Cl2-2-IPA. The
      absolute configurations of both the 5,6-Cl2-2-IPA enantiomers were determined by
      comparing the 1H-NMR spectra of their diastereomeric (S)-(-)-1-phenylethyl esters
      with those of the diastereomeric (S)-(-)-1-phenylethyl esters of 2-(3
      indolyl)propionic acid (2-IPA) whose absolute configurations are already known.
      There was no essential difference between (S)-(+)- and (R)-(-)-5,6-Cl2-2-IPA in
      hypocotyl growth-inhibiting activity toward Chinese cabbage, but their inhibitory
      activities were stronger than that of the potent mother auxin, 5,6-Cl2-IAA. No
      essential difference in the coleoptile elongating activity of Avena sativa was
      apparent for the enantiomers, this activity being about one-third that of 5,6-Cl2
      IAA.

PMID- 11302159
TI  - Storage-dependent degradation of 57-kDa protein in royal jelly: a possible marker
      for freshness.
AB  - In order to find a marker for freshness of royal jelly (RJ), the composition
      change of RJ during storage was investigated. The contents of 10-hydroxy-2
      decenoic acid, a bioactive component of RJ, and several vitamins did not change
      during storage at 40 degrees C for 7 days. However, a specific protein,
      designated royal jelly protein-1 (RJP-1), was gradually degraded during storage
      under various conditions (from 4 degrees C to 50 degrees C for up to 7 days). The
      specific degradation of RJP-1 was proportional to storage temperature and storage
      period. RJP-1 was purified to homogeneity and characterized as a monomeric
      glycoprotein with a molecular mass of 57 kDa. These results suggest that 57-kDa
      protein in RJ can be used as a marker for freshness of RJ, reflecting the
      conditions under which RJ has been stored.

PMID- 11302160
TI  - Identification of collagen as a new fish allergen.
AB  - This study was intended to identify a high molecular weight allergen that had
      been detected in fish. Analyses by ELISA of five protein fractions prepared from
      bigeye tuna muscle showed that the high molecular weight allergen was contained
      in the myostromal protein fraction. Based on the results of SDS-PAGE,
      immunoblotting and amino acid analysis of the myostromal protein fraction, the
      high molecular weight allergen was judged to be collagen. Five of the eight
      patient sera used were found to react to the bigeye tuna collagen. In competitive
      ELISA inhibition experiments, the bigeye tuna collagen almost completely
      inhibited the IgE reactivity to the heated extracts from five species of fish,
      suggesting that collagen is commonly allergic regardless of fish species.
      However, no antigenic cross-reactivity was observed between collagens from fish
      and other animals.

PMID- 11302161
TI  - Conformational change in a single molecular species, beta3, of beta-conglycinin
      in acidic ethanol solution.
AB  - Several physicochemical experiments were done to obtain further information on
      the conformational changes occurring in beta-conglycinin in acidic-ethanol
      solution, using a single molecular species of this protein, beta3. By far-UV
      circular dichroism (CD), a transition from beta-sheet to alpha-helical structure
      was observed upon addition of acidic-ethanol, and the alpha-helix content was
      found to reach 76% in 70% ethanol (pH 2). From analyses of near-UV CD and
      difference absorption spectra, it was found that the tertiary structure of the
      beta3 species was significantly altered at ethanol concentrations between 10 and
      20%. The profiles of binding of 1-anilinonaphthalene-8-sulfonic acid to the beta3
      species during acidic-ethanol denaturation were indicative of the existence of
      intermediate conformers in the molten globule-like denaturation state. By
      measuring Fourier transform infrared spectra and estimating the Stokes radius by
      dynamic light scattering, the beta3 molecules were found to aggregate with an
      increase in ethanol concentration.

PMID- 11302162
TI  - Kinetic analysis of microbial desulfurization of model and light gas oils
      containing multiple alkyl dibenzothiophenes.
AB  - The reaction mechanism of biodesulfurization was investigated using whole cells
      of Rhodococcus erythropolis KA2-5-1, which have the ability to convert
      dibenzothiophene (DBT) into 2-hydroxybiphenyl. The desulfurization patterns of
      alkyl DBTs were represented by the Michaeis-Menten equation. The values of rate
      constants, the limiting maximal velocity (Vmax) and Michaelis constant (Km), for
      desulfurization of alkyl DBTs were calculated. The relative desulfurization
      activities of various alkyl DBTs were reduced in proportion to the total carbon
      numbers of alkyl substituent groups. Alkyl DBTs that had a total of six carbons
      of alkyl substituent groups were not desulfurized. The type or position of alkyl
      substituent groups had little effect on desulfurization activity. The
      desulfurization activity of each alkyl DBT, when mixed together, was reduced.
      This phenomenon was caused by apparent competitive inhibition of substrates.
      Using the apparent competitive inhibition model, the desulfurization pattern of a
      multiple components system containing alkyl DBTs was elucidated. This model was
      also applicable for biodesulfurization of light gas oil.

PMID- 11302163
TI  - Synthesis of the enantiomers of some methyl-branched cuticular hydrocarbons of
      the ant, Diacamma sp..
AB  - The enantiomers of 3-methylpentacosane, 3-methylheptacosane, 3-methylnonacosane,
      13-methylheptacosane, and 5-methylheptacosane were synthesized by starting from
      the enantiomers of 2-methylbutyl bromide or citronellol. These methyl-branched
      alkanes are the characteristic components of the cuticular hydrocarbons of queen
      of the ant, Diacamma sp..

PMID- 11302164
TI  - Interactions of dietary fats and proteins on fatty acid composition of immune
      cells and LTB4 production by peritoneal exudate cells of rats.
AB  - The interaction of dietary fats and proteins on lipid parameters of rats was
      studied using safflower oil (linoleic acid-rich), borage oil (gamma-linolenic
      acid-rich) or perilla oil (alpha-linolenic acid-rich) in combination with casein
      or soybean protein. The experiment was focused on the fatty acid composition of
      immune cells and the leukotriene B4 production by peritoneal exudate cells. Serum
      total cholesterol, triglyceride, and phospholipid levels were low in perilla oil
      fed or soybean protein-fed rats. Fatty acid compositions of serum and liver
      phospholipids reflected those of dietary fats. However, feeding borage oil
      resulted in a marked increase in the proportion of dihomo-gamma-linolenic acid in
      phospholipids of peritoneal exudate cells, spleen lymphocytes, and mesenteric
      lymph node lymphocytes in relation to those of liver and serum. It is suggested
      that activities of metabolic n-6 polyunsaturated fatty acids are different
      between immune and other tissues. In addition, the magnitude of the reduction of
      the proportion of linoleic acid of perilla oil in immune cells was considerably
      more moderate than serum and liver, indicating a different degree of interference
      of alpha-linolenic acid with linoleic acid metabolism. Leukotriene release from
      peritoneal exudate cells was in the order of safflower oil > borage oil > perilla
      oil groups as reflecting the proportion of arachidonic acid, and tended to be
      lower in soybean protein-fed groups. These suggest an anti-inflammatory property
      of gamma-linolenic acid as well as alpha-linolenic acid tended to be strengthened
      when they were combined with soybean protein than with casein.

PMID- 11302165
TI  - Molecular cloning, DNA sequence, and expression of the gene encoding for
      thermostable pectate lyase of thermophilic Bacillus sp. TS 47.
AB  - The gene that encodes a thermostable pectate lyase (called PL 47), from Bacillus
      sp. TS 47, was cloned, sequenced, and expressed in mesophilic B. subtilis. The
      gene contained an open reading frame consisting of 1326 bp, which encoded 441
      amino acids. The deduced amino acid sequence of the mature enzyme (416 amino
      acids with a calculated molecular mass of 47,262 Da), showed 52% similarity with
      PL (BsPel) from mesophilic B. subtilis SO113. The structure-based alignment of
      the deduced amino acid sequence of PL 47 with that of BsPel suggested that PL 47
      might have a parallel beta-helix structure with three long loops. The amino acids
      making up PL 47 are richer in hydrophobic amino acids and glutamic acid than
      BsPel. The hydropathy profile of PL 47 indicated that the amino acid sequences
      around putative calcium binding sites are more hydrophobic than the same region
      of BsPel. The gene product expressed in B. subtilis as the host was stable up to
      70 degrees C and the reaction was optimal around 70 degrees C, as well as native
      PL 47.

PMID- 11302166
TI  - Growth of nisin-producing lactococci in cooked rice supplemented with soybean
      extract and its application to inhibition of Bacillus subtilis in rice miso.
AB  - Lactic acid fermentation of cooked rice and rice koji by supplementation with
      soybean extract (SBE) and its application to rice miso fermentation were
      investigated. By supplementing the cooked rice with SBE, lactic acid bacteria
      (LAB) grew well without any unfavorable effects on the rice such as off-flavor or
      coloration. Lactococcus lactis subsp. lactis IFO12007 (Lc. lactis, a producer of
      the bacteriocin nisin) proliferated at 10(8 to approximately 9) cells/g after 24
      h of incubation and produced high activity of nisin. The fermented rice with Lc.
      lactis strongly inhibited not only Bacillus subtilis ATCC19659 but also the other
      Bacillus strains. While some strains of LAB markedly inhibited the growth of Asp.
      oryzae, resulting in failure of koji fermentation, Lc. lactis did not affect the
      growth of these molds. When Lc. lactis was used for rice miso fermentation as a
      lactic acid starter culture, Lc. lactis rapidly proliferated and produced high
      nisin activity of 6,400 IU/g, in the steamed rice, resulting in complete growth
      inhibition of B. subtilis, which had been inoculated at the beginning of the koji
      fermentation. The rice miso after 12 weeks of aging had a suitable pH, and
      favorable taste and color. Furthermore, hyposalting of rice miso could be done
      without difficulty by lactic acid fermentation of both rice and soybeans.

PMID- 11302167
TI  - LysR-type transcriptional regulator ChiR is essential for production of all
      chitinases and a chitin-binding protein, CBP21, in Serratia marcescens 2170.
AB  - To identify the genes required for chitinase production by Serratia marcescens
      2170, various Tn5 mutants somehow defective in chitinase production were isolated
      in a previous study. In order to identify the mutated gene in one of the
      chitinase-deficient mutants, N1, DNA regions flanking the Tn5 insertion were
      cloned and sequenced. Sequence comparison showed that the mutation occurred in
      the ORF located between chiB and cbp, which encode chitinase B and chitin-binding
      protein CBP21, respectively. The ORF encodes a 313-amino acid polypeptide which
      has significant similarity with various LysR-type transcriptional regulators, and
      thus the gene was designated chiR. Targeted mutagenesis confirmed that disruption
      of the chiR gene results in the phenotype of N1. Gel mobility shift assays using
      partially purified ChiR protein demonstrated that this protein specifically binds
      to the intergenic region between chiR and cbp. These results strongly suggest
      that ChiR is a LysR-type transcriptional regulator which is essential for
      production of all chitinases and CBP21.

PMID- 11302168
TI  - Changes in hematological parameters of athletes after receiving daily dose of a
      mixture of 12 amino acids for one month during the middle- and long-distance
      running training.
AB  - Previous studies have shown that a mixture of amino acids, consisting of 9
      essential amino acids and 3 non-essential amino acids was effective in
      facilitating muscle recovery from athletic activities. In this study, the
      objective was to determine whether this amino acid mixture improved the physical
      condition and associated blood parameters of athletes in training when
      administered for a prolonged period. Thirteen college middle- and long-distance
      runners were placed in a 6-month experiment and received the amino acid mixture
      at the dose of 2.2 g/day for one month, 4.4 g/day for one month, and 6.6 g/day
      for one month with washout periods between test periods. The physical condition
      was scored and blood samples were collected before and after each test period.
      When the subjects received 2.2 g of the amino acid mixture three times a day, the
      physical condition was significantly improved along with increases in red blood
      cell count, hemoglobin, hematocrit, serum albumin, and fasting glucose, and a
      decrease in creatine phophokinase (p<0.05), suggesting increased hematopoiesis
      and glycogenesis, and rapid alleviation of muscle inflammation by the amino acid
      mixture.

PMID- 11302169
TI  - Characterization of a metalloenzyme from a wild mushroom, Tricholoma saponaceum.
AB  - Two kinds of metalloendopeptidases from the fruiting bodies of Tricholoma
      saponaceum (TSMEP1 and TSMEP2) have been purified, and TSMEP1 has been
      characterized based on their fibrinolytic activity. The enzymes have the same N
      terminal amino acid sequence, Ala-Leu-Tyr-Val-Gly-X-Ser-Pro-X-Gln-Gln-Ser-Leu-Leu
      Val, but slightly different molecular weights of 18,147 and 17,947, as measured
      by matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass
      spectrometry. The N-terminal sequence do not match with any known protein or open
      reading frame. TSMEP1 hydrolyzes fibrinogen as well as fibrin, but does not show
      any proteolytic activity for other blood proteins such as thrombin, human
      albumin, human IgG, hemoglobin, or urokinase. The enzyme hydrolyzes both A alpha
      and B beta subunits of human fibrinogen with equal efficiency but didn't show any
      reactivity for the gamma form of human fibrinogen. The enzymatic activity is
      strongly inhibited by EDTA and 1,10-phenanthroline, indicating that the enzymes
      are metalloproteases. No inhibition was found with phenylmethylsulfonyl fluoride
      (PMSF), L-trans-epoxysuccinyl leucylamido-(4-guanidino)-butane (E-64), pepstatin
      and 2-mercaptoethanol. The activity of the purified enzyme was increased by Mg2+,
      Fe2+, Zn2+, and Co2+, and slightly decreased by Ca2+, but the enzyme activity was
      dramatically decreased by Cu2+, and totally inhibited by Hg2+. It has broad
      substrate specificity for synthetic peptides, and keep the high activity from pH
      7.5 to 9, suggesting that the purified enzyme was a basic protease. The enzyme
      was stable up to 30 degrees C and the maximum fibrinolytic activity was at 55
      degrees C.

PMID- 11302170
TI  - Antitumor effect of photodynamic therapy with zincphyrin, zinc-coproporphyrin
      III, in mice.
AB  - We studied the antitumor effects of photodynamic therapy (PDT) with Zincphyrin,
      coproporphyrin III with zinc, derived from Streptomyces sp. AC8007, in vitro and
      in vivo. The photokilling effect of Zincphyrin in the presence of 0.78-100
      microg/ml with visible light of 27.2 mW x min/cm2 for 10 min was lower than the
      hematoporphyrin (Hp) used as a control with L5178Y or sarcoma-180 cells. On the
      other hand, Zincphyrin apparently reduced tumor growth after intraperitoneal
      injection at doses of 12.5-50 mg/kg with light irradiation of 75.48 mW x min/cm2
      for 10 min in sarcoma-180-bearing mice. Although no mice treated with Zincphyrin
      died, Hp did cause the death of mice. In B-16 melanoma-bearing mice, both
      Zincphyrin and Hp had a similar phototherapic effect. Further improvement of the
      phototherapic effect was observed with the continuous administration of
      Zincphyrin at 12.5 mg/kg per day for 3 days. The concentration of Zincphyrin in
      the serum reached a maximum level of 16 microg/ml within 20 min, and the
      concentration remained at 4.2 microg/ml at 1 hour after the onset of treatment,
      indicating its rapid action in the body. No animals died after the
      intraperitoneal administration of Zincphyrin at 100 mg/kg plus exposure to light
      of 10 mW x min/cm2 for 2 hours, and the body weight of the mice did not decrease.
      In contrast, all animals receiving 100 mg/kg of Hp under the same conditions
      died. These results indicate that Zincphyrin would be a useful photosensitizer
      with low phototoxicity.

PMID- 11302171
TI  - Feeding unsaponifiable compounds from rice bran oil does not alter hepatic mRNA
      abundance for cholesterol metabolism-related proteins in hypercholesterolemic
      rats.
AB  - The hypocholesterolemic effect of rice bran oil (RBO) is defined in human and
      animal experiments which indicate the presence of active component(s) in the
      unsaponifiable fraction, but the detailed mechanism is not known yet. Exogenously
      hypercholesterolemic (ExHC) rats were fed for 2 weeks on a 0.5% cholesterol diet
      supplemented with 10% each of RBO, RBO-simulated oil (RBOSO) in its fatty acid
      composition, or RBOSO plus 0.25% unsaponifiable compounds (UC) from RBO. Rats fed
      RBO or the UC resulted in lowing serum and liver cholesterol concentration and
      preventing reduction of high density lipoproteinic-cholesterol. Dietary RBO or
      the UC led to an elevation of fecal neutral sterol excretion, but no significant
      change in fecal bile acid excretion or in hepatic abundance of mRNAs for 3
      hydroxy-3-methylglutaryl-CoA reductase, cholesterol-7alpha-hydroxylase, and low
      density lipoprotein receptor. Besides, serum and liver alpha-tocopherol
      concentrations were lowered in RBO or the UC-fed rats. These results show that
      the UC in RBO leads to a decreased serum cholesterol concentration by
      interrupting the absorption of intestinal hydrophobic compounds rather than by
      modifying cholesterol metabolism in the liver.

PMID- 11302172
TI  - Occurrence of 11-hydroxyjasmonic acid glucoside in leaflets of potato plants
      (Solanum tuberosum L.).
AB  - In order to examine the occurrence of 11-hydroxyjasmonic acid glucoside in potato
      plants, a synthesis of 11-hydroxyjasmonic acid was accomplished, and the
      synthetic compound was employed as a standard for an LC-SIM analysis. The
      existence of 11-hydroxyjasmonic acid glucoside was proved by the LC-SIM analysis.

PMID- 11302173
TI  - A transgenic apple callus showing reduced polyphenol oxidase activity and lower
      browning potential.
AB  - Polyphenol oxidase (PPO) is responsible for enzymatic browning of apples. Apples
      lacking PPO activity might be useful not only for the food industry but also for
      studies of the metabolism of polyphenols and the function of PPO. Transgenic
      apple calli were prepared by using Agrobacterium tumefaciens carrying the
      kanamycin (KM) resistant gene and antisense PPO gene. Four KM-resistant callus
      lines were obtained from 356 leaf explants. Among these transgenic calli, three
      calli grew on the medium containing KM at the same rate as non-transgenic callus
      on the medium without KM. One callus line had an antisense PPO gene, in which the
      amount and activity of PPO were reduced to half the amount and activity in non
      transgenic callus. The browning potential of this line, which was estimated by
      adding chlorogenic acid, was also half the browning potential of non-transgenic
      callus.

PMID- 11302174
TI  - Construction of a chimeric shuttle plasmid via a heterodimer system: secretion of
      an scFv protein from Bacillus brevis cells capable of inhibiting
      hemagglutination.
AB  - Passive immunization is an attractive therapy for preventing oral diseases
      including dental caries and periodontal disease. For this purpose, we attempted
      to produce a single chain variable fragment, scFv, which inhibited
      hemagglutination using the Bacillus brevis protein-producing system. To
      accomplish this, a novel strategy, a heterodimer system, was used for the
      construction of a chimeric shuttle plasmid. Initially, a set of new plasmids,
      kanamycin-resistant donor and erythromycin-resistant general cloning plasmids,
      were constructed. p15A ori was a common replication origin in these plasmids,
      while the pUB110 rep and minus origin (MO) were cloned into the donor plasmid.
      Next, the secretion domain of the B. subtilis alpha-amylase gene and the G2-4
      gene, coding for the scFv protein, were cloned into the general cloning plasmid
      and fused by PCR. Both the donor plasmid and the general cloning plasmid
      containing the fused gene were digested with NotI and them ligated, a dimeric
      plasmid being constructed. The key restriction sites, AscI, are arranged such
      that the pUB110 rep-MO moiety was switched from the donor to the general cloning
      plasmid following AscI digestion. The chimeric shuttle plasmid was readily
      constructed by simple re-circularization and a B. brevis transformant producing
      the scFv protein in the culture fluid was isolated.

PMID- 11302175
TI  - Effects of buckwheat in a renal ischemia-reperfusion model.
AB  - Experiments were done to find whether buckwheat extract ameliorates the renal
      injury induced by ischemia-reperfusion. In ischemic-reperfused control rats, the
      activities of antioxidative enzymes in renal tissue and blood and renal
      parameters deviated from the normal range, indicating dysfunction of the kidneys.
      In contrast, when buckwheat extract was given orally for 20 consecutive days
      before ischemia and reperfusion, the activities of the antioxidation enzymes
      superoxide dismutase, catalase, and glutathione peroxidase were higher, while
      thiobarbituric acid-reactive substance levels in serum and renal tissue were
      lower in the treated rats than in the controls. Decreased levels of urea nitrogen
      and creatinine in serum demonstrated a protective effect against the renal
      dysfunction caused by ischemia and recirculation. On the other hand, it was
      demonstrated that buckwheat extract had a protective effect on cultured proximal
      tubule cells subjected to hypoxia-reoxygenation, probably by preventing oxygen
      free radicals from attacking the cell membranes.

PMID- 11302176
TI  - The deletion of amino-terminal domain in Thermoactinomyces vulgaris R-47 alpha
      amylases: effects of domain N on activity, specificity, stability and
      dimerization.
AB  - Thermoactinomyces vulgaris R-47 alpha-amylases, TVA I and TVA II, have a domain
      N, which is an extra structure in the family 13 enzymes. To investigate the roles
      of domain N in TVAs, we constructed TVAs-deltaN mutants which are deleted in
      domain N, and Y14,16,68A and Y41,82,95A mutants of TVA II. TVAs-deltaN were
      unstable under alkaline conditions, and their thermal stabilities were 10 degrees
      C lower than that of wild-types. The specific activities of TVAs-deltaN for
      pullulan, starch, cyclodextrins, and oligosaccharides were drastically decreased,
      being about 1,500- to 10,000-fold smaller than those of wild-types. The kcat
      values of Y14,16,68A and Y41,82,95A for all tested substrates were markedly
      decreased, and the Km value of Y14,16,68A for alpha-CD and maltotriose were 25-
      and 3-fold larger, and that of Y41,82,92A for starch was 10-fold larger than that
      of the wild-type. TVA I and TVAs-deltaN in solution are a monomer, while TVA II
      is a homo-dimer, calculated by their molecular masses. These results suggest
      domain N in TVAs is an important structure for stabilization of enzymes,
      recognition and hydrolysis of substrates, and dimerization of TVA II.

PMID- 11302177
TI  - Sweetness of sweet protein thaumatin is more thermoresistant under acid
      conditions than under neutral or alkaline conditions.
AB  - Thermostability of thaumatin and mechanisms of thermoinactivation were examined
      at 80 degrees C in the pH range from 2 to 10. The sweetness of thaumatin
      disappeared on heating at pH above 7 for 15 min, but the sweetness remained even
      after heating at 80 degrees C for 4 h at pH 2. This indicated that the sweet
      protein thaumatin is more thermoresistant under acid conditions than under
      neutral or alkaline conditions. Prolonged heating of thaumatin under acid
      conditions slowly reduced sweetness, and produced a heterogeneous population of
      molecules, all of which was soluble and monomeric. The resultant molecules were
      clearly distinct from those generated by heating at pH above 7. Hydrolysis of
      peptide bonds and other irreversible chemical reactions slowly took place in the
      molecule heated under acid conditions, and it would be, in part, a cause of
      thermoinactivation of thaumatin under acid conditions. The thermostability of
      thaumatin and the mechanism of thermoinactivation were largely dependent on pH.

PMID- 11302178
TI  - Inhibition of Vero cell cytotoxic activity in Escherichia coli O157:H7 lysates by
      globotriaosylceramide, Gb3, from bovine milk.
AB  - In order to clarify the presence and verotoxin (VT) inhibitory activity of
      globotriaosylceramide (Gb3) in bovine milk, we analyzed neutral
      glycosphingolipids (GSLs) from bovine milk and investigated the inhibitory effect
      of bovine milk Gb3 on the cytotoxicity of VT2. Five species of neutral GSLs,
      designated as N-1, N-2, N-3, N-4, and N-5, were separated on thin-layer
      chromatography (TLC). N-1, N-2, and N-3 showed the same mobility as
      glucosylceramide, lactosylceramide, and Gb3 on the TLC plate, respectively. N-4
      and N-5 GSLs migrated below globoside on the TLC plate. N-3 GSL having the same
      TLC mobility as Gb3 from bovine milk was immunologically identified as Gb3 by
      monoclonal antibody against Gb3, anti-CD77 monoclonal antibody. Furthermore, the
      effect of bovine milk Gb3 on VT2-induced cytotoxicity was investigated. We found
      that treatment of VT2 with bovine milk Gb3 can reduce the cytotoxic effect of
      VT2.

PMID- 11302179
TI  - Characterization of the pro-aminopeptidase from Aeromonas caviae T-64.
AB  - The pro-aminopeptidase from Aeromonas caviae T-64 (pro-apAC) had maximal activity
      at 60 degrees C and was more stable than mature apAC at temperature up to 65
      degrees C for 1 hour. The pH stability of pro-apAC ranged from 4.0 to 8.0, which
      is broader than the range for the mature apAC. The kcat/Km of pro-apAC was 1.4%
      to 24% of that of mature apAC.

PMID- 11302180
TI  - Purification and characterization of an aminopeptidase from the edible
      basidiomycete Grifola frondosa.
AB  - An aminopeptidase was purified 178-fold from an extract of Grifola frondosa by
      ammonium sulfate precipitation and a series of column chromatographies on phenyl
      Toyopearl, Sephadex G-25, and Mono-Q. The molecular mass of the enzyme was
      estimated to be 27 kDa and 30 kDa by gel filtration and SDS-PAGE, respectively.
      The enzyme had an optimum pH of 8.5 and was stable between pH 6.0 and pH 10.5,
      and it also had a high level of heat stability. The enzyme was inactivated by
      EDTA and o-phenanthroline, and it was also strongly inhibited by bestatin, but no
      inhibitory effect of DFP was observed. The enzyme preferentially hydrolyzed
      peptides containing hydrophobic residues in the N-terminal position.

PMID- 11302181
TI  - Induction of nitric oxide synthase and subsequent production of nitric oxide not
      involved in interferon-gamma-induced hyperpermeability of Caco-2 intestinal
      epithelial monolayers.
AB  - Caco-2 cell monolayers exposed to 1000 U/ml interferon-gamma (IFN-gamma) for 6
      days elicited inducible nitric oxide synthase (iNOS) expression and increased
      translayer permeability. This iNOS increase was blocked by
      pyrrolidinedithiocarbamate (an inhibitor of iNOS induction) but it did not
      suppress the hyperpermeability response. Furthermore, 2,2'
      (hydroxynitrosohydrazino) bis-ethanamine (a NO donor) did not increase monolayer
      permeability. Therefore, IFN-gamma-induced hyperpermeability is not due to its
      induction of iNOS activity and resulting increases in NO levels.

PMID- 11302182
TI  - Lack of effect of the abnormal fatty acid metabolism in NC/Nga mice on their
      atopic dermatitis.
AB  - Although clinical evidence has suggested that dysregulated fatty acid metabolism
      is associated with atopic disorders, the molecular basis for such a correlation
      remains to be demonstrated. In the present study, we analyzed the fatty acid
      composition in peripheral blood cells of NC/Nga mice, a model for atopic
      dermatitis (AD). We found that arachidonic acid significantly accumulated in mice
      with the AD manifestation. In addition, the leucotriene B4-releasing ability upon
      calcium ionophore A23187 stimulation was potentiated in blood cells. An
      arachidonic acid accumulation was not apparent in the non-atopic BALB/c strain,
      but was still observed in healthy NC/Nga mice fed under specific pathogen-free
      conditions. These results indicate that a disturbed fatty acid metabolism in
      NC/Nga mice was not a trigger factor for their dermatitis development.

PMID- 11302183
TI  - Occurrence of a novel lyase catalyzing beta-elimination reaction toward threo-3
      chloro-L-aspartate in Pseudomonas putida TPU 7151.
AB  - A bacterium, Pseudomonas putida TPU 7151, which degrades threo-3-chloro-L
      aspartate, was isolated from soil and the enzyme responsible for the degradation
      of the amino acid was partially purified from the cell-free extract of the
      strain. The enzyme, which required PLP for its reaction, catalyzed a
      stoichiometric beta-elimination reaction of threo-3-chloro-L-aspartate to form
      oxaloacetate, Cl-, and NH4. The enzyme was active toward only threo-3-chloro-L
      aspartate and L-cysteine, but did not catalyze a beta-replacement reaction. The
      enzyme can be classified in a new group of PLP-dependent amino acid-lyases [EC
      4.2.1.-].

PMID- 11302184
TI  - Production of galactooligosaccharides from lactose using a beta-glucosidase from
      Thermus sp. Z-1.
AB  - A thermostable beta-glucosidase from Thermus sp. Z-1 that not only hydrolyzes
      beta-glucosides but also beta-galactosides was shown to efficiently produce
      oligosaccharides during hydrolysis of lactose. The yield of oligosaccharides was
      more than 40% for 0.88 M lactose solution at 70 degrees C at pH 7.0. The major
      product was a trisaccharide, 3'-galactosyllactose, formed by a galactosyltransfer
      reaction.

PMID- 11302185
TI  - Isolation and identification of 2-phenylethyl disaccharide glycosides and mono
      glycosides from rose flowers, and their potential role in scent formation.
AB  - 2-Phenylethyl 6-O-alpha-L-arabinofuranosyl-beta-D-glucopyranoside (1), and its 6
      O-beta-D-xylopyraranosyl-beta-D-glucopyranoside (2) were identified in the
      flowers of Rosa damascena Mill. harvested at the full bloom stage. 2-Phenylethyl
      beta-D-glucopyranoside (3) and its beta-D-galactopyranoside (4) together with 1
      and 2 were also found in the flower buds harvested 44 hrs before the opening
      stage. Their potential role in scent formation is discussed.

PMID- 11302186
TI  - A simple and rapid method for intra- and interspecific transformation of Bacillus
      subtilis on solid media by DNA in protoplast lysates.
AB  - A simple method for intra- and interspecific transformation of Bacillus subtilis
      on solid media has been devised with DNA in protoplast lysates, 0.8% agar,
      glutamate, and yeast extract. The transformation frequency is 2.3 x 10(3)
      transformants per microg DNA, 10-20 times higher than that for conventional
      transformation on solid media. The method can be applicable to transformation in
      microtiter plates.

PMID- 11302187
TI  - An in vitro approach to the evaluation of the cross talk between intestinal
      epithelium and macrophages.
AB  - The intestinal epithelium acts as a mucosal barrier by varying their signals to
      immune cells within the intestine. To observe the cross talk between intestinal
      epithelium and macrophages, we establish a Caco-2-THP-1 co-culture system. Using
      this co-culture system, we suggested that paracrine factors of intestinal
      epithelium increased the phagocytic capacity of intestinal monocytes/macrophages
      to be ready for immune and inflammatory responses.

PMID- 11302188
TI  - Inhibitory activity of berberine on DNA strand cleavage induced by hydrogen
      peroxide and cytochrome c.
AB  - The inhibitory activity of berberine on the DNA single-strand cleavage induced by
      hydrogen peroxide and cytochrome c was measured. Berberine effectively inhibited
      single-strand cleavage of DNA and its effectiveness was concentration-dependent.
      As the berberine concentration increased, the inhibitory activity against the DNA
      single-strand cleavage increased. The treatments with 1, 5, 10, 50, and 100
      microM berberine showed 7.7, 10.8, 32.2, 39.5, and 51.6% inhibition of DNA
      cleavage. This inhibitory activity of berberine against the DNA single-strand
      cleavage has never been reported previously. The inhibitory activity of berberine
      against DNA cleavage was stronger than caffeic acid and ascorbic acid. Berberine
      did not show strong hydroxyl radical scavenging activity, but showed strong
      superoxide anion radical quenching ability.

PMID- 11302189
TI  - Isolation and characterization of the Enterobacter cloacae cheR mutant defective
      in phosphate taxis.
AB  - A chemotaxis-defective mutant of Enterobacter cloacae IFO3320, designated EC1,
      was isolated after N-methyl-N'-nitro-N-nitrosoguanidine (NTG) mutagenesis.
      Computer-assisted capillary assays showed that EC1 failed to show chemotactic
      responses to peptone and inorganic phosphate (Pi). Cloning and sequence analysis
      showed that EC1 is a cheR mutant, suggesting that Pi taxis by E. cloacae is
      dependent on a methyl-accepting chemotaxis protein(s) (MCP). EC1 was further
      mutagenized with NTG to construct cheR pstS and cheR pstA double mutants. A
      recombinant plasmid pECT01.2, which contained the E. cloacae cheR gene, restored
      the ability of these double mutants to show chemotaxis toward peptone but not Pi.
      These results suggest that the phosphate-specific transport (Pst) system,
      together with a MCP(s), is required for detecting Pi in E. cloacae.

PMID- 11302190
TI  - Apoptosis-inducing activity of high molecular weight fractions of tea extracts.
AB  - High molecular weight fractions of green tea, black tea, oolong tea, and pu-erh
      tea were found to induce apoptosis in human monoblastic leukemia U937 cells by
      examination of their ability to inhibit cell proliferation and to induce
      apoptotic body formation and DNA ladder formation. These tea fractions were also
      shown to induce apoptosis in stomach cancer MKN-45 cells. In addition to known
      antitumor-promoting activity of tea high molecular weight fractions, their
      apoptosis-inducing activity may contribute to cancer chemopreventive effects of
      tea.

PMID- 11302191
TI  - Synthesis and absolute configuration of MQ-A3 [1-(14'-methylhexadecanoyl)
      pyrrolidine], a novel aliphatic pyrrolidine amide from the tropical
      convolvulaceous species.
AB  - A novel pyrrolidine amide (MQ-A3) isolated from the tropical convolvulaceous
      species was synthesized in 5 steps by starting from commercially available 12
      bromododecanol and (S)-2-methylbutylbromide. The absolute configuration of the
      natural product was confirmed by a comparison of the specific rotation values.

PMID- 11302192
TI  - Dietary curdlan increases proliferation of bifidobacteria in the cecum of rats.
AB  - Significant increases in the amounts of short-chain fatty acids and lactate, and
      in numbers of bifidobacteria were observed in the cecum of curdlan (CD) -fed rats
      as compared with those of cellulose-fed ones. The in vitro proliferation of 5
      species of bifidobacteria was markedly increased in the cultures containing the
      supernatant obtained from the cecal contents of CD-fed rats. These findings
      suggest that bifidus factors have been produced in the cecum of CD-fed rats.

PMID- 11302193
TI  - Production of monoclonal antibody against Scrippsiella trochoidea cysts and its
      application to analysis during cyst formation and enzyme-linked immunosorbent
      assay.
AB  - A monoclonal antibody was produced by the fusion of mouse myeloma cells with
      spleen cells from a mouse immunized with the cysts of Scrippsiella trochoidea,
      marine phytoplankton. Immunofluorescence microscopic observation showed that the
      antibody reacted with the spines on the cyst but not with the vegetative cells
      and cyst walls. An enzyme-linked immunosorbent assay could be used to measure the
      cysts in muddy bottom sediments using the purified antibody conjugated with
      horseradish peroxidase.

PMID- 11302194
TI  - Aplysiallene, a new bromoallene as an Na, K-ATPase inhibitor from the sea hare,
      Aplysia kurodai.
AB  - A new bromoallene metabolite, named aplysiallene, was isolated from the Japanese
      sea hare, Aplysia kurodai, as an Na, K-ATPase inhibitor. Its structure was
      elucidated by spectroscopic methods. The known metabolites, laurinterol and
      debromolaurinterol, isolated from this animal were also evaluated for their Na, K
      ATPase inhibitory activity.

PMID- 11302195
TI  - A simultaneous assay method for L-glutamate and L-pyroglutamate contents in soy
      sauce using a 5-oxoprolinase (without ATP hydrolyzing activity).
AB  - L-Glutamine and L-glutamate, which are important flavor components in soy sauce,
      are converted to L-pyroglutamate during brewing. Therefore, it is necessary that
      the L-glutamate and L-pyroglutamate contents can be measured accurately. We
      developed a simultaneous assay method for L-glutamate and L-pyroglutamate by
      using 5-oxoprolinase (without ATP hydrolyzing activity) and glutamate oxidase. By
      this method, the L-pyroglutamate could be measured accurately in a range of 0.05
      to 1.0 mM in the presence of 1.0 mM L-glutamate. This system is effective for
      process and quality controls.

PMID- 11302196
TI  - Actinidic acid, a new triterpene phytoalexin from unripe kiwi fruit.
AB  - Seven phytoalexins (1-7), including a new compound, were isolated from the peel
      of unripe kiwi fruit (Actinidia deliciosa cv. Golden King) that had been wounded
      and inoculated with Colletotrichum musae. The new phytoalexin (1) was identified
      as 2alpha,3beta,23-trihydroxy-12,20(30)-ursadien-28-oic acid, and named actinidic
      acid. Phytoalexins 2-6 are known triterpenes but have not previously been
      described as phytoalexins. Phytoalexin 7 is the same triterpene as the
      phytoalexin of nectarine fruit.

PMID- 11302197
TI  - (-)-Semivioxanthin, a new abscisic active compound against Hinoki cypress leaves
      isolated from Cryptosporiopsis abietina.
AB  - The new naphthopyrone, (-)-semivioxanthin (1) was isolated from Cryptosporiopsis
      abietina. The structure of 1 was determined as the reversed optical isomer of
      semivioxanthin by comparing its spectroscopic data with those of semivioxanthin.
      Compound 1 exhibited abscisic activity against Hinoki cypress leaves and
      antifungal activity against Cladosporium herbarum.

PMID- 11302198
TI  - Secondary metabolites from a Streptomyces strain isolated from Livingston Island,
      Antarctica.
AB  - The producing strain Streptomyces sp. 1010 was isolated from a shallow sea
      sediment from the region of Livingston Island, Antarctica. From the culture broth
      of this strain naturally active secondary metabolites were isolated identical to
      phthalic acid diethyl ester (C12H14O4, MW. 222); 1, 3-bis (3
      phenoxyphenoxy)benzene (C30H22O4, MW.446); hexanedioic acid dioctyl ester
      (C22H42O4, MW.370) and the new substance 2-amino- 9, 13 -dimethyl heptadecanoic
      acid (C19H39NO2, MW.313). These compounds represent diverse classes of chemical
      structures and provide evidence for the untapped biosynthetic potential of marine
      bacteria from Antarctica.

PMID- 11302199
TI  - Mariannaepyrone--a new inhibitor of thromboxane A2 induced platelet aggregation.
AB  - Mariannaeapyrone ((E)-2-(1,3,5,7-tetramethyl-5-nonenyl)-3,5-dimethyl-6-hydroxy-4H
      pyran-4-one) is a new fungal metabolite isolated from fermentations of the common
      mycophilic deuteromycete Mariannaea elegans. The chemical structure of the 4
      pyrone was determined by spectroscopic techniques. Mariannaeapyrone is a
      selective inhibitor of the thromboxane A2 induced aggregation of human platelets,
      whereas only weak cytotoxic and antimicrobial effects could be observed.

PMID- 11302200
TI  - Pathogenesis of carbon tetrachloride-induced hepatocyte injury bioactivation of
      CCI4 by cytochrome P450 and effects on lipid homeostasis.
AB  - The CCl4-induced development of liver damage was studied in monolayer cultures of
      primary rat hepatocytes: (1) CCl4 caused accumulation of triglycerides in
      hepatocytes following cytochrome P450 induction with beta-naphthoflavone or
      metyrapone. Ethanol or a high dose of insulin plus triiodothyronine had the same
      effect. (2) CCl4 increased the synthesis of fatty acids and triglycerides and the
      rate of lipid esterification. Cholesterol and phospholipid synthesis from acetate
      was also increased. (3) CCl4 reduced beta-oxidation of fatty acids as assessed by
      CO2-release and ketone body formation. Hydrolysis of triglycerides was also
      reduced. (4) The content of unsaturated fatty acids in microsomal lipids was
      decreased by almost 50% after incubation with CCl4, while saturated fatty acids
      increased slightly. (5) CCl4 exerted a pronounced inhibitory effect on the
      exocytosis of macromolecules (albumin), but did not affect secretion of bile
      acids from hepatocytes.

PMID- 11302201
TI  - Carbohydrate structures of haptoglobin in sera of healthy people and a patient
      with congenital disorder of glycosylation.
AB  - Haptoglobin is one of acute phase glycoproteins often used as markers in
      glycopathology studies. In this work the oligosaccharide structures of
      haptoglobin from 'healthy' subjects have been studied in detail, taking into
      consideration the possible dependence of glycosylation on the phenotype. About
      75% of charged haptoglobin glycans were of biantennary complex structure, and
      some of them lacked one terminal sialic acid molecule. Triantennary structures
      made up almost 25% of the charged glycans pool, and highly branched
      tetrasialylated oligosaccharides did not exceed 1%. The main difference between
      haptoglobin derived from the sample of pooled 44 sera and from the 2-2 phenotype
      individual concerned the relative content of trisialylated oligosaccharide with
      one 2-3 linked sialic acid residue. The oligosaccharide profile of haptoglobin
      derived from serum of a patient suffering from congenital disorder of
      glycosylation was compared to 'healthy' controls. It was shown, that four main
      glycans are identical in patient and 'normal' haptoglobins. Some alterations were
      found in the relative content of mono-, bi-, and trisialylated glycans as well as
      in the appearance of some tracely abundant oligosaccharides in haptoglobin of the
      patient with congenital disorder of glycosylation.

PMID- 11302202
TI  - Characterization of the polyphenolic composition of purple loosestrife (Lythrum
      salicaria).
AB  - Phenolic compounds of purple loosestrife (Lythrum salicaria L.) were analysed by
      the use of liquid chromatography-mass spectrometry (LC/MS) equipped with
      atmospheric pressure chemical ionisation (APCI) and electrospray ionisation
      (ESI). The presence of vitexin and orientin as well as their isomers, isovitexin
      and isoorientin, were confirmed using ion trap multiple stage LC/MS3 analysis.
      Several phenolic acids and tannins were also detected. Ellagitannins, vescalagin
      and pedunculagin, are reported from the plant for the first time.

PMID- 11302203
TI  - Effects of L-phenylalanine on acetylcholinesterase, (Na+,K+)-ATPase and Mg2+
      ATPase activities in adult rat whole brain and frontal cortex.
AB  - The effect of different L-phenylalanine (Phe) concentrations (0.12-12.1 mM) on
      acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg2+-ATPase activities was
      investigated in homogenates of adult rat whole brain and frontal cortex at 37
      degrees C. AChE, (Na+,K+)-ATPase and Mg2+-ATPase activities were determined after
      preincubation with Phe. AChE activity in both tissues showed a decrease up to 18%
      (p<0.01) with Phe. Whole brain Na+,K+-ATPase was stimulated by 30-35% (p<0.01)
      with high Phe concentrations, while frontal cortex Na+,K+-ATPase was stimulated
      by 50-55% (p<0.001). Mg2+-ATPase activity was increased only in frontal cortex
      with high Phe concentrations. It is suggested that: a) The inhibitory effect of
      Phe on brain AChE is not influenced by developmental factors, while the
      stimulation of Phe on brain Na+,K+-ATPase is indeed affected; b) The stimulatory
      effect of Phe on rat whole brain Na+,K+-ATPase is decreased with age; c) Na+,K+
      ATPase is selectively more stimulated by high Phe concentrations in frontal
      cortex than in whole brain homogenate; d) High (toxic) Phe concentrations can
      affect Mg2+-ATPase activity in frontal cortex, but not in whole brain, thus
      modulating the amount of intracellular Mg2+.

PMID- 11302204
TI  - Enhanced nucleophilicity and depressed electrophilicity of peroxide by zinc(II),
      aluminum(III) and lanthanum(III) ions.
AB  - The binuclear zinc(II) complex, [Zn2(HPTP)(CH3COO)]2+ was found highly active to
      cleave DNA (double-strand super-coiled DNA, pBR322 and phix174) in the presence
      of hydrogen peroxide. However, no TBARS (2-thiobarbituric acid reactive
      substance) formation was detected in a solution containing 2-deoxyribose (or 2'
      deoxyguanosine, etc); where (HPTP) represents N,N,N'-N'-tetrakis(2-pyridylmethyl)
      1,3-diamino-2-propanol. These facts imply that DNA cleavage reaction by the
      binuclear Zn(II)/H2O2 system should be due to a hydrolytic mechanism, which may
      be attributed to the enhanced nucleophilicity but depressed electrophilicity of
      the peroxide ion coordinated to the zinc(II) ion. DFT (density-functional theory)
      calculations on the peroxide adduct of monomeric zinc(II) have supported the
      above consideration. Similar DFT calculations on the peroxide adducts of the
      Al(III) and La(III) compounds have revealed that electrophilicity of the peroxide
      ion in these compounds is strongly reduced. This gives an important information
      to elucidate the fact that La3+ can enhance the growth of plants under certain
      conditions.

PMID- 11302205
TI  - Electronic property and reactivity of (hydroperoxo)metal compounds.
AB  - DFT calculations were done for the (hydroperoxo)metal complexes with eta1
      coordination mode, where metal ions are Fe(III), Al(III), Cu(II) and Zn(II).
      Results shows that 1) the electron density at the two oxygen atoms of the
      hydroperoxide ion is highly dependent on the angle O-O-H in M-OOH species and the
      difference in electron density between the two oxygen atoms reaches a maximum at
      the angle O-O-H = 180 degrees, 2) total electron density at the two oxygen atoms
      of the peroxide ion increases by approach of methane to the (hydroperoxo)metal
      species in the cases of Fe(III) and Cu(II); on the other hand, significant
      decrease of the electron density on peroxide oxygen atoms was observed for the
      cases of Al(III) and Zn(II) compounds. These findings suggest that the
      (hydroperoxo)metal species acts as an electrophile in the former cases (M =
      Fe(III), Cu(II)) and as a nucleophile for the latter two compounds (M = Zn(II),
      Al(III)). The electrophilicity observed for the Fe(III) and Cu(II) complexes is
      attributed to the presence of unoccupied- or half-filled d-orbitals interacting
      with the hydroperoxide ion. 3) Two oxygen atoms of the (hydroperoxo)-compounds of
      Fe(III) and Cu(II) complexes exhibit quite different reactivity toward the
      substrate, such as methane. When methane approaches the oxygen atom which is
      coordinated to a metal ion, a strong decrease of electron density at the methane
      carbon atom occurs with concomitant increase of electron density at the peroxide
      oxygen atoms inducing its heterolytic O-O cleavage. When methane approaches the
      terminal oxygen atom, an oxidative coupling reaction occurs between peroxide ion
      and methane; at first a nucleophilic attack by the terminal electron-rich oxygen
      atom occurs at the carbon atom to induce C-O bond formation, and a subsequent
      oxidative electron transfer proceeds from substrate to the metal-peroxide species
      yielding CH3-OOH, CH3OH, or other oxidized products. These results clearly
      demonstrate that the (hydroperoxo)-metal compound itself is a rather stable
      compound, and activation of the peroxide ion is induced by interaction with the
      substrate, and the products obtained by the oxygenation reaction are dependent on
      the chemical property of the substrate, redox property of a metal ion, and
      stability of the compounds formed in the intermediate process.

PMID- 11302206
TI  - Micellization process--temperature influence on the counterion effect.
AB  - The micellization process of dodecyltrimethylammonium chloride (DTAC) and bromide
      (DTAB) was studied at 313 K. Nuclear magnetic resonance and calorimetric methods
      were used. The calorimetric titration curves permitted determination of the
      critical micelle concentration (CMC) and enthalpy of the micellization process
      (deltaHm) of the compounds studied. The results obtained were compared to those
      obtained at 298 K. It was found that calorimetric curves obtained at 313 K for
      both compounds were similar to each other in contrast to 298 K. Especially a
      great difference in the shape of curves was observed for DTAC. NMR (1H NMR and
      13C NMR) spectra were taken below and above the CMC values and chemical shifts
      (delta) analysed as a function of concentration of the compounds. Comparison of
      chemical shift-concentration plots with those obtained from measurements
      performed at lower temperature showed that chemical shifts are of very similar
      character in both cases for analyzed groups. However, there are some quantitative
      differences that indicate at smaller difference in hydration of DTAB and DTAC
      micelles at elevated temperature. This may be the reason of decrease of
      differences between micellization processes of DTAC and DTAB compounds. The
      smaller hydration may be, in turn, the result of diminishing differences in
      physicochemical properties of bromide and chloride ions with temperature.

PMID- 11302207
TI  - A comparative chemical study of Maytenus ilicifolia mart. reiss and Maytenus
      robusta reiss (Celastraceae).
AB  - This work describes a comparative qualitative and quantitative chemical analysis
      of Maytenus ilicifolia and Maytenus robusta (Celastraceae), extracts by high
      resolution gas chromatography (HRGC), using external standards as the method of
      determination and thin layer chromatographic (TLC). The results show that both
      plants have a similar chromatographic profile. However, M. robusta exhibited
      about three times higher concentration of triterpene friedelin than M.
      ilicifolia.

PMID- 11302208
TI  - Quinolizidine alkaloid profiles of Lupinus varius orientalis, L. albus albus, L.
      hartwegii, and L. densiflorus.
AB  - Alkaloid profiles of two Lupinus species growing naturally in Egypt (L. albus
      albus [synonym L. termis], L. varius orientalis) in addition to two New World
      species (L. hartwegii, L. densiflorus) which were cultivated in Egypt were
      studied by capillary GLC and GLC-mass spectrometry with respect to quinolizidine
      alkaloids. Altogether 44 quinolizidine, bipiperidyl and proto-indole alkaloids
      were identified; 29 in L. albus, 13 in L. varius orientalis, 15 in L. hartwegii,
      6 in L. densiflorus. Some of these alkaloids were identified for the first time
      in these plants. The alkaloidal patterns of various plant organs (leaves,
      flowers, stems, roots, pods and seeds) are documented. Screening for
      antimicrobial activity of these plant extracts demonstrated substantial activity
      against Candida albicans, Aspergillus flavus and Bacillus subtilis.

PMID- 11302209
TI  - Coprinol, a new antibiotic cuparane from a Coprinus species.
AB  - Coprinol, a new antibacterial cuparane, was isolated from fermentations of a
      Coprinus sp. Its biological activities were investigated and its structure was
      elucidated by spectroscopic methods. The new antibiotic exhibited activitiy
      against multidrug-resistant Gram-positive bacteria in vitro. Two derivatives were
      synthesized and their activities compared to the parent compound.

PMID- 11302210
TI  - Volatile compounds of cashew apple (Anacardium occidentale L.).
AB  - The volatile compounds of a largely consumed Brazilian cashew apple variety
      (Anacardium occidentale L. var. nanum, Anacardiaceae) were recovered by headspace
      extraction or simultaneous distillation-extraction. Several compounds including
      esters (29), terpenes (16), hydrocarbons (9), carboxylic acids (7), aldehydes
      (7), alcohols (3), ketones (2), lactones (2) and norisoprenoids (1) were
      characterized and quantified by gas chromatography-mass spectrometry analyses.

PMID- 11302211
TI  - Chemical composition of turmeric oil--a byproduct from turmeric oleoresin
      industry and its inhibitory activity against different fungi.
AB  - Curcumin, the yellow coloring pigment of turmeric is produced industrially from
      turmeric oleoresin. The mother liquor after isolation of curcumin from oleoresin
      known as curcumin removed turmeric oleoresin (CRTO) was extracted three times
      with n-hexane at room temperature for 30 min to obtain turmeric oil. The turmeric
      oil was subjected to fractional distillation under vacuum to get two fractions.
      These fractions were tested for antifugal activity against Aspergillus flavus, A.
      parasiticus, Fusarium moniliforme and Penicillium digitatum by spore germination
      method. Fraction II was found to be more active. The chemical constituents of
      turmeric oil, fraction I and fraction II were determined by GC and identified by
      GC-MS. Aromatic turmerone, turmerone and curlone were major compounds present in
      fraction II along with other oxygenated compounds.

PMID- 11302212
TI  - Cytotoxic triterpenoids from Erica andevalensis.
AB  - The cytotoxic activity of two pentacyclic triterpenoids (ursolic acid and alpha
      amyrine) isolated from the methanolic extract of the aerial parts from Erica
      andevalensis, whose structures have been established on the basis of
      spectroscopic and chemical evidence, has been assessed against three human cancer
      cell lines, TK-10 (renal adenocarcinoma), MCF-7 (breast adenocarcinoma) and UACC
      62 (melanoma), recommended by NCI (National Cancer Institute) and we also
      evaluated the antimitotic effect in root meristematic cells of Allium cepa.
      Ursolic acid was found to possess the highest cytotoxic activity.

PMID- 11302213
TI  - New semisynthetic antimicrobial labdane-type diterpenoids derived from the resin
      "ladano" of Cistus creticus.
AB  - The antimicrobial activity of fifteen semisynthetic labdane-type diterpenes
      derived from the two major natural compounds 3 and 4 of the resin "ladano" of
      Cistus creticus is reported. The chloroethyl carbamidic esters 15 and 20 showed
      the strongest antimicrobial activity against Gram(+), Gram(-) bacteria and
      pathogenic fungi.

PMID- 11302214
TI  - The influence of newly synthesised fenporpimorph derivatives on some pathogen
      yeasts.
AB  - The effect of minimum inhibitory concentrations (MICs) of six novel fenpropimorph
      derivatives on lipid and sterol composition of Candida albicans, Cryptococcus
      neoformans, Malassezia pachydermatis and Malassezia furfur was investigated. The
      MICs for the most effective derivatives were found in the range from 3.7 to 56.7
      microM and were 2-3 times lower compared to the commercial fungicide bifonazol.
      The more efficient fenpropimorph derivatives were the piperidine derivative for
      C. albicans and the allylamine derivative for Cr. neoformans, M. pachydermatis
      and M. furfur. The inhibitor in the growth medium reduced the unsaturation index
      of the total lipid content in M. furfur and C. albicans.

PMID- 11302215
TI  - Screening of biotransformation products of carvone enantiomers by headspace
      SPME/GC-MS.
AB  - In the course of our continuing work on transformation of monoterpenes by
      microorganisms, the biotransformation of (+)- and (-)-carvone was carried out.
      The metabolites formed during microbial transformations were screened using a
      simple, rapid and efficient technique: Headspace-solid phase microextraction
      (SPME)/GC-MS. The results as well as the application of this technique are
      described.

PMID- 11302216
TI  - Neodictyoprolenol and dictyoprolenol, the possible biosynthetic intermediates of
      dictyopterenes, in the Japanese brown algae Dictyopteris.
AB  - Neodictyoprolenol [(-)-(3S)-(1,5Z,8Z)-undecatrien-3-ol] and dictyoprolenol [(-)
      (3S)-(1,5Z,8Z)-undecadien-3-ol]), which had been proposed as possible
      biosynthetic intermediates of the sex pheromones of marine brown algae such as
      dictyopterene B [(-)-trans-1-((1'E,3'Z)-hexadienyl)-2-vinylcyclopropane], D' [(+)
      6-((1'Z)-butenyl)-1,4-cycloheptadiene] and C' [(+)-6-butyl-1,4-cycloheptadiene],
      were again identified in the essential oils from Dictyopteris prolifera, D.
      latiscula, and in D. undulata, together with the C11-related volatile compounds
      such as neodictyoprolene, dictyoprolene and dictyopterenes. Incubation of D.
      prolifela preparation with racemic neodictyoprolenol and dictyoprolenol as
      substrates showed (S)-enantioselective decreases of the added substrates and
      increases in dictyopterenes. From these results, a possible pathway to form
      dictyopterenes is discussed.

PMID- 11302217
TI  - Early elicitor-induced events in chickpea cells: functional links between
      oxidative burst, sequential occurrence of extracellular alkalinisation and
      acidification, K+/H+ exchange and defence-related gene activation.
AB  - Elicitation of cultured chickpea (Cicer arietinum L.) cells stimulates a signal
      transduction pathway leading to several rapid responses: (1) oxidative burst, (2)
      extracellular alkalinisation, (3) extracellular acidification, (4) transient K+
      efflux, and (5) activation of defence related genes all within 2 hours. Induced
      genes are encoding acidic and basic chitinases, a thaumatin-like protein and
      isoflavone reductase. All these elicitor-induced responses are inhibited by the
      Ser/Thr protein kinase inhibitor staurosporine and the anion channel blocker
      anthracene-9-carboxylic acid but stimulated by the Ser/Thr protein phosphatase 2A
      inhibitor cantharidin. The oxidative burst leads to a transient extracellular
      H2O2 accumulation which seems to be preceded by O2- production, indicating
      dismutation of O2- to H2O2. The oxidative burst is accompanied by transient
      alkalinisation of the culture medium which is followed by long-lasting
      extracellular acidification. An 80 percent inhibition of the alkalinisation after
      complete inhibition of the H2O2 burst with diphenylene iodonium indicates that
      the elicitor induced increase of extracellular pH is mainly based on a proton
      consumption for O2-dismutation. A simultaneous deactivation of the plasma
      membrane H+-ATPase during oxidative burst and extracellular alkalinisation is
      also suggested. The elicitor-stimulated extracellular acidification is inhibited
      by the plasma membrane H+-ATPase inhibitor N, N'-dicyclohexylcarbodiimide
      assuming a reactivation of the H+-ATPase 25 min after elicitation. Extracellular
      acidification seems not to be necessary for elicitor-induced activation of
      defence related genes. Opposite modulation of K+ and proton fluxes after
      elicitation and/or treatment with the H+-ATPase effectors fusicoccin or N, N'
      dicyclohexylcarbodiimide indicate that the elicitor induced transient K+ efflux
      is regulated by a K+/H+ exchange reaction.

PMID- 11302218
TI  - Phase response curve for the ultradian rhythm of the lateral leaflets of
      Desmodium gyrans using DC current pulses.
AB  - In the present study the leaf movement rhythm was perturbed by the application of
      DC current pulses (15 microA, 10 seconds, voltage applied: 10 V) to the upper
      part of the pulvinus, passing through the pulvinus and its stalk. The pulses were
      applied at four different positions of the leaflets: when the leaves were at the
      lowermost position, when moving up, at the uppermost position and when moving
      down. The pre-perturbed and the post-perturbed rhythms were compared. We found
      that the rhythms were shifted in phase and the phase shifts observed at the four
      different positions of the leaflets were significantly different in magnitude as
      well as direction. Furthermore, we could also observe phase advances, which is in
      contrast to an earlier finding. A phase response curve (PRC) was constructed to
      illustrate the sensitivity of the oscillating leaflet system to DC pulses.
      Substantial delays of about 50 s (as compared to the period of about 200 s) were
      obtained when pulses were administered at the lowermost position and when leaflet
      were moving upwards, while advances or no phase shifts were recorded in the
      uppermost position and when leaflet were moving down respectively.

PMID- 11302219
TI  - Egyptian propolis: 1-antimicrobial activity and chemical composition of Upper
      Egypt propolis.
AB  - The antimicrobial activity of four propolis samples collected from Upper Egypt
      against Staphylococcus aureus; Escherichia coli and Candida albicans was
      evaluated. There was a variation in the antimicrobial activity according to the
      propolis origin. Banisweif propolis showed the highest antimicrobial activity
      against Staphylococcus aureus, Escherichia coli and Candida albicans, but Fayoum
      propolis had moderate activity against all tested pathogens. Propolis collected
      from Assiut and Souhag gave lower antimicrobial activity. Propolis samples were
      investigated by GC/MS, 71 compounds were identified, 14 being new for propolis.
      Banisweif propolis is characterized by the presence of 7 caffeate esters and 4
      triterpenoids. Fayoum propolis showed the highest amount of lactic acid and the
      presence of 3 chalcones. But Assiut propolis is characterized by the presence of
      4 prenylated coumarates. Souhag propolis is characterized by the presence of 5
      aliphatic dicarboxylic acids and some other new compounds to propolis.

PMID- 11302220
TI  - Influence of food and larval age on the defensive chemistry of Saturnia pyri.
AB  - Scolus secretions and hemolymph of caterpillars of Saturnia pyri fed with two
      different foodplants (Crataegis monogyna, Prunus spinosa) were chemically
      analyzed and their chemical similarities determined. The secondary-compound
      patterns obtained for the two body fluids showed no significant differences when
      compared between the two groups of alternatively fed last-instar larvae. Thus,
      the composition of these fluids of full-grown caterpillars is not influenced by
      the larval diet. However, younger larvae on P. spinosa revealed a diversity of
      compounds differing significantly from that of larger caterpillars fed with
      either C. monogyna (both body fluids) or P. spinosa (hemolymph only). This
      indicates that, on the one hand, the hemolymph composition is adapted to the
      changing physiological requirements of the given instars whereas, on the other
      hand, the defensive mixtures remain unaltered in the late larval instars due to a
      constant spectrum of potential enemies.

PMID- 11302221
TI  - Insect growth regulatory activity of some extracts and compounds from Parthenium
      argentatum on fall armyworm Spodoptera frugiperda.
AB  - The methanolic extract from aerial parts of Parthenium argentatum, afforded
      argentatin A and B. These compounds were evaluated for their effect on the fall
      armyworm (Spodoptera frugiperda). Toosendanin, a commercial insecticide derived
      from Melia azedarach was used as positive control. When tested for activity,
      using neonate larvae into the no-choice artificial diet bioassays, argentatin A,
      argentatin B and methanol extract caused significant growth inhibitory activity
      with GC50 of 17.8, 36.1 and 6.4 ppm at 7 days, respectively, and increased the
      development time of surviving larvae in a concentration-dependent manner with RGI
      values of 0.40, 0.60 and 0.26, at 25.0, 25.0 and 5.0 ppm, respectively. In
      addition, it was possible to observe in most of the treated groups a significant
      delay in the time of pupation, adult emergence and deformities. Acute toxicity
      against adults of S. frugiperda was also found, MeOH extract had the most potent
      activity with LD50 value of 3.10 ppm. In addition, MeOH extract and argentatin A
      caused acetylcholinesterase inhibition of 93.7% and 90.0%, at 5.0 and 50.0 ppm,
      respectively; whereas argentatin B had only slight inhibitory activity.
      Therefore, the MeOH extract was identified as insecticidal extract from P.
      argentatum with activity at concentrations above 15.0 ppm.

PMID- 11302222
TI  - Looking forward and looking back: integrating completion and sunk-cost effects
      within an escalation-of-commitment progress decision.
AB  - Currently, there are 2 conflicting frameworks with which to understand why
      decision makers might escalate their commitment to a previously chosen course of
      action: sunk costs and project completion. The author proposes that sunk costs
      and need to complete exert simultaneous pressures, both independent and
      interactive, on a decision maker's level of commitment. The responses of 340
      participants were analyzed and supported a complementary relationship between the
      2 predictors. In addition, sunk costs demonstrated a curvilinear influence on
      commitment and an interaction with level of completion that supported a Level of
      Completion x Sunk Cost moderation model. (A marginal utility model was not
      supported.) Results are discussed in terms of their relevance toward offering a
      complementary view of 2 potential antecedents to a decision maker's propensity to
      escalate his or her commitment to a previously chosen course of action.

PMID- 11302223
TI  - Accounting for common method variance in cross-sectional research designs.
AB  - Cross-sectional studies of attitude-behavior relationships are vulnerable to the
      inflation of correlations by common method variance (CMV). Here, a model is
      presented that allows partial correlation analysis to adjust the observed
      correlations for CMV contamination and determine if conclusions about the
      statistical and practical significance of a predictor have been influenced by the
      presence of CMV. This method also suggests procedures for designing
      questionnaires to increase the precision of this adjustment.

PMID- 11302224
TI  - Investigating the influence of social desirability on personality factor
      structure.
AB  - This study provides a comprehensive investigation into whether social
      desirability alters the factor structure of personality measures. The study
      brought together 4 large data sets wherein different organizational samples
      responded to different personality measures. This facilitated conducting 4
      separate yet parallel investigations. Within each data set, individuals
      identified through a social desirability scale as responding in an honest manner
      were grouped together, and individuals identified as responding in a highly
      socially desirable manner were grouped together. Using various analyses, the fit
      of higher order factor structure models was compared across the 2 groups. Results
      were the same for each data set. Social desirability had little influence on the
      higher order factor structures that characterized the relationships among the
      scales of the personality measures.

PMID- 11302225
TI  - Can performance-feedback accuracy be improved? Effects of rater priming and
      rating-scale format on rating accuracy.
AB  - Performance appraisal information is often used for employee feedback and
      development. Research has found that assessments that are global (i.e., based on
      broad aspects of performance) and comparative (i.e., explicit interratee
      comparisons) may be most accurate in terms of Cronbach's (1955) differential
      accuracy, a type of accuracy that is directly relevant to the provision of
      feedback. Unfortunately, a global-comparative assessment may not give recipients
      the most useful diagnostic feedback. In this experiment, an innovative rater
      priming manipulation was developed and tested on a sample of 109 participants.
      The priming manipulation had the effect of improving differential accuracy and
      providing diagnostic feedback. A 2nd independent variable involving 2 different
      Behavioral Observation Scale formats also was investigated. Explanations of
      findings, limitations of this experiment, directions for future research, and
      implications for performance appraisal practice are discussed.

PMID- 11302226
TI  - Risk propensity differences between entrepreneurs and managers: a meta-analytic
      review.
AB  - Research examining the relative risk-taking propensities of entrepreneurs and
      managers has produced conflicting findings and no consensus, posing an impediment
      to theory development. To overcome the limitations of narrative reviews, the
      authors used psychometric meta-analysis to mathematically cumulate the literature
      concerning risk propensity differences between entrepreneurs and managers.
      Results indicate that the risk propensity of entrepreneurs is greater than that
      of managers. Moreover, there are larger differences between entrepreneurs whose
      primary goal is venture growth versus those whose focus is on producing family
      income. Results also underscore the importance of precise construct definitions
      and rigorous measurement.

PMID- 11302227
TI  - Workplace justice, citizenship behavior, and turnover intentions in a union
      context: examining the mediating role of perceived union support and union
      instrumentality.
AB  - This study examined the relationship between workplace justice afforded by the
      grievance system and the union outcomes of citizenship behavior and turnover
      intentions and the mechanisms that underpin these relationships. Respondents (N =
      187) were members of a large public sector union in Singapore. Results revealed
      that perceived union support and union instrumentality fully mediated the
      relationship between the dimensions of workplace justice and citizenship behavior
      directed toward the union (OCBO) and citizenship behavior directed at other union
      members (OCBI). Union instrumentality partially mediated the procedural justice
      turnover intentions relationship.

PMID- 11302228
TI  - The effect of item content overlap on organizational commitment questionnaire-
      turnover cognitions relationships.
AB  - This study examined the effect of overlapping scale content when certain items in
      the Organizational Commitment Questionnaire (OCQ) are used to predict turnover
      cognition measures. Analyses of judgmental data collected from 25 subject matter
      experts suggested that 6 OCQ items reflected a desire or an intent to retain
      membership in one's organization. Confirmatory factor analyses of survey data
      from 172 master of business administration alumni showed that the 6 OCQ retention
      items shared overlapping content with turnover cognitions items. Hierarchical
      multiple regression analyses of survey data from 330 hotel managers showed that
      (a) removing the 6 OCQ retention items caused a significant decrease in the
      variance explained in a measure of turnover cognitions and (b) the size of this
      effect is larger than that suggested by previous work.

PMID- 11302229
TI  - Organizational efforts to affirm sexual diversity: a cross-level examination.
AB  - A growing number of organizations have enacted policies intended to recognize and
      affirm sexual diversity in the workforce. This research demonstrates that the
      more prevalent these policies, the less likely sexual minority members are to
      experience treatment discrimination. Further, as expected, more equitable
      treatment was associated with higher levels of satisfaction and commitment among
      lesbian and gay employees. Treatment discrimination was also systematically
      related to the use of 3 identity management strategies (i.e., counterfeiting,
      avoiding, integrating). Findings also illustrate the importance of considering
      individual attributes in diversity research. In particular, group identity
      attitudes were associated with work-related attitudes and identity management.
      Overall, the research demonstrates the importance of organizational efforts to
      affirm sexual diversity and highlights the need for future research in this area.

PMID- 11302230
TI  - A comparison of attitude, personality, and knowledge predictors of service
      oriented organizational citizenship behaviors.
AB  - Attitude, personality, and customer knowledge antecedents were compared in their
      predictive ability of 3 service-oriented forms of employee organizational
      citizenship behaviors (OCBs): loyalty, service delivery, and participation. For
      the 1st study, 236 customer-contact employees provided data concerning their OCBs
      and the attitude, personality, and knowledge antecedents. The 2nd investigation
      relied on data provided by 144 contact employees from a network of university
      libraries. Using hierarchical regression in both studies, the authors found that
      each of the 3 types of service-oriented OCBs was best predicted by different
      subsets of the antecedents. Job attitudes accounted for the most unique variance
      in loyalty OCBs, personality accounted for the most unique variance in service
      delivery OCBs, and customer knowledge and personality jointly were the best
      predictors of participation OCBs.

PMID- 11302231
TI  - Is everyone in agreement? An exploration of within-group agreement in employee
      perceptions of the work environment.
AB  - Multilevel researchers often gather individual-level data to measure group-level
      constructs. Within-group agreement is a key consideration in the measurement of
      such constructs, yet antecedents of within-group agreement have been little
      studied. The authors found that group member social interaction and work
      interdependence were significantly positively related to within-group agreement
      regarding perceptions of the work environment. Demographic heterogeneity was not
      significantly related to within-group agreement. Survey wording showed a complex
      relationship to agreement. Both evaluative items and socially undesirable items
      generated high within-group agreement. The use of a group rather than individual
      referent increased within-group agreement in response to descriptive items but
      decreased within-group agreement in response to evaluative items. Items with a
      group referent showed greater between-group variability than items with an
      individual referent.

PMID- 11302232
TI  - Reciprocation of perceived organizational support.
AB  - Four hundred thirteen postal employees were surveyed to investigate
      reciprocation's role in the relationships of perceived organizational support
      (POS) with employees' affective organizational commitment and job performance.
      The authors found that (a) POS was positively related to employees' felt
      obligation to care about the organization's welfare and to help the organization
      reach its objectives; (b) felt obligation mediated the associations of POS with
      affective commitment, organizational spontaneity, and in-role performance; and
      (c) the relationship between POS and felt obligation increased with employees'
      acceptance of the reciprocity norm as applied to work organizations. Positive
      mood also mediated the relationships of POS with affective commitment and
      organizational spontaneity. The pattern of findings is consistent with
      organizational support theory's assumption that POS strengthens affective
      commitment and performance by a reciprocation process.

PMID- 11302233
TI  - How employees respond to personal offense: the effects of blame attribution,
      victim status, and offender status on revenge and reconciliation in the
      workplace.
AB  - This study investigated the relationships between blame, victim and offender
      status, and the pursuit of revenge or reconciliation after a personal offense.
      Results from a sample of 141 government agency employees showed that blame is
      positively related to revenge and negatively related to reconciliation. In
      addition, victim-offender relative status moderated the relation between blame
      and revenge such that victims who blamed sought revenge more often when the
      offender's status was lower than their own. The victims' own absolute
      hierarchical status also moderated this relation such that lower, not higher,
      status employees who blamed sought revenge more often.

PMID- 11302234
TI  - The stability of validity coefficients over time: Ackerman's (1988) model and the
      general aptitude test battery.
AB  - This study examined P. L. Ackerman's (1988) model of skill acquisition within an
      applied setting. Differences were examined between jobs on the basis of task
      consistency: changes in performance variability across experience, learning
      curves, and stability of ability-performance correlations across experience.
      Results showed the degree of task consistency influenced the shape of learning
      curves, with jobs composed of primarily consistent tasks improving more rapidly
      and reaching asymptote sooner. In addition, trends in ability-performance
      correlations were moderated by the degree of task consistency within ajob.
      Specifically, forjobs with primarily consistent tasks, general cognitive ability
      best predicted early performance whereas psychomotor ability best predicted later
      performance. In contrast, general cognitive ability was the strongest predictor
      across experience for jobs with primarily inconsistent tasks.

PMID- 11302235
TI  - Relationship of core self-evaluations traits--self-esteem, generalized self
      efficacy, locus of control, and emotional stability--with job satisfaction and
      job performance: a meta-analysis.
AB  - This article presents meta-analytic results of the relationship of 4 traits--self
      esteem, generalized self-efficacy, locus of control, and emotional stability (low
      neuroticism) with job satisfaction and job performance. With respect to job
      satisfaction, the estimated true score correlations were .26 for self-esteem, .45
      for generalized self-efficacy, .32 for internal locus of control, and .24 for
      emotional stability. With respect to job performance, the correlations were .26
      for self-esteem, .23 for generalized self-efficacy, .22 for internal locus of
      control, and .19 for emotional stability. In total, the results based on 274
      correlations suggest that these traits are among the best dispositional
      predictors of job satisfaction and job performance. T. A. Judge, E. A. Locke. and
      C. C. Durham's (1997) theory of core self-evaluations is used as a framework for
      discussing similarities between the 4 traits and their relationships to
      satisfaction and performance.

PMID- 11302236
TI  - Recognition instructions and recognition practice can alter the confidence-
      response time relationship.
AB  - Three face-recognition experiments examined how instructions for a recognition
      test (e.g., emphasize speed or emphasize accuracy) can impact the confidence
      response time relationship for episodic memory reports. In all 3 experiments, the
      confidence-response time correlation was smaller when participants were told to
      speed up their responding rate, which suggests that participants in these
      conditions relied less on the artificially compressed response times in forming
      their confidence judgments than they would under "normal" circumstances. Also,
      recognition practice before the final memory test eliminated the effect of the
      recognition instruction manipulation. These results support J. S. Shaw's (1996)
      suggestion that witnesses rely in part on the fluency of their memory reports
      when generating confidence judgments, and these findings have important
      implications for understanding the relationships among witness confidence,
      accuracy, and response time.

PMID- 11302237
TI  - Alteration of argyrophilic nucleolar organizer region associated (Ag-NOR)
      proteins in apoptosis-induced human salivary gland cells and human oral squamous
      carcinoma cells.
AB  - The level of argyrophilic nucleolar organizer regions (AgNORs) and AgNOR
      associated proteins (Ag-NOR proteins) varies with cell activity, including
      ribosomal biogenesis occurring in proliferating cells. Proteins associated with
      some AgNORs are detected by a specific silver staining. To investigate a possible
      relationship between apoptosis and the AgNORs or Ag-NOR proteins, we examined the
      changes of AgNORs and Ag-NOR proteins during apoptosis in a human salivary gland
      cell line, HSG cells, and a human oral squamous carcinoma cell line, SCC-25
      cells. Apoptosis was induced by treatment of HSG and SCC-25 cells with okadaic
      acid. Proteins prepared from HSG and SCC-25 cells treated with varying
      concentrations of okadaic acid (OA) were subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) followed by transferring to
      transfer membranes and staining for Ag-NOR proteins by modified Western blot
      analysis. Four major bands (110 kDa, 43 kDa, 39kDa, and 37 kDa) were detected in
      the proteins obtained from the control cells. The level of the 110-kDa protein
      decreased in the proteins prepared from OA-induced apoptotic cells; however, the
      reaction intensity of the other three bands was changed in apoptotic cells. An
      additional band of an 80-kDa Ag-NOR protein appeared and increased in the
      apoptotic cells. Cellular fractionation of HSG cells and SCC-25 cells was done
      with or without apoptotic induction. An 80-kDa Ag-NOR protein was detected in the
      nuclear fraction prepared from the apoptotic cells, while the 110-kDa protein
      decreased in the nuclear fraction of these cells. The 110-kDa Ag-NOR protein may
      be nucleolin (C23) as deduced from its AgNOR staining features, including
      molecular weight. The 80-kDa protein may be the cleavage product of the 110-kDa
      protein. In the cell-free apoptotic system, in which intact nuclei of HSG cells
      were incubated with the cytosol fraction of apoptotic HSG and SCC-25 cells, the
      80-kDa Ag-NOR protein was detected in nuclei incubated with the cytosol fraction
      of apoptotic cells, while the level of the 110-kDa protein decreased. The changes
      of Ag-NOR proteins in nuclei prepared from SCC-25 cells incubated with cytosol
      fractions prepared from HSG and SCC-25 cells were identical to those of the HSG
      cells. The alternation of AgNORs in apoptosis-induced HSG cells was also examined
      using double staining with Hoechst 33342 and silver nitrate. Hoechst staining
      revealed typical apoptotic nuclei, which exhibited highly fluorescent condensed
      chromatin in OA-treated HSG cells. Silver grains representing AgNORs were not
      detected in the cells undergoing apoptosis. The dual-imposition view confirmed
      that AgNORs, which are visible as dots in nucleoli in the control cells,
      disappeared from the apoptotic nuclei of HSG cells. Our results indicate that the
      110-kDa nucleolar Ag-NOR protein is associated with apoptosis and is cleaved
      during apoptosis.

PMID- 11302238
TI  - Diffusion of reduced arecoline and arecaidine through human vaginal and buccal
      mucosa.
AB  - Because alkaloids from areca nut, arecoline and arecaidine, have been implicated
      in the development of oral submucous fibrosis, we determined their diffusion
      kinetics through human buccal and vaginal mucosa. Four clinically healthy vaginal
      mucosa specimens (mean patient age +/- standard deviation: 47 +/- 15 years; age
      range: 31-60 years) and 4 buccal mucosa specimens from 2 male patients and 2
      female patients (mean patient age +/- standard deviation: 31 +/- 9 years; age
      range: 17-53 years) were obtained during surgery. In vitro flux rates of reduced
      arecoline and arecaidine (r-arecoline and r-arecaidine) were determined by use of
      a flow-through diffusion apparatus. Analysis of variance, a Duncan multiple range
      test, and an unpaired t-test were used to determine steady state kinetics and
      flux differences over time intervals. Although statistically significant
      differences were observed between flux values for both alkaloids and tissues at
      certain time points, these were not considered to be of biological (clinical)
      significance. However, the flux rates across both mucosa of r-arecoline were
      significantly higher statistically than those of rarecaidine. The findings
      demonstrated the differences in the diffusion kinetics between r-arecoline and r
      arecaidine across human buccal and vaginal mucosa, an observation that could be
      explained in terms of their ionisation characteristics. Additionally, the results
      obtained further support the hypothesis that human vaginal mucosa can be used as
      a model for buccal mucosa in studies of permeability to various chemical
      compounds.

PMID- 11302239
TI  - A molecular epidemiological study of sequential oral isolates of Candida albicans
      from terminally ill patients.
AB  - The pattern of candidal colonisation was studied in a group of terminally ill
      patients receiving antifungal treatment for oral candidosis. A total of 43
      isolates of C. albicans was collected pre- and post-antifungal treatment from
      patients up to a maximum period of 4 weeks. Isolates were analysed by
      electrophoretic karyotyping (EK) and by inter-repeat polymerase chain reaction
      (IR-PCR). Fifteen electrophoretic karyotypes and 17 IR-PCR profiles were
      identified. Sequential isolates from 10 patients yielded identical profiles in
      both EKs and IR-PCR analyses. In the case of four patients, minor differences in
      the profiles were obtained by either EK or IR-PCR. The findings suggest that
      antifungal treatment in this patient group fails to eradicate the original C.
      albicans strain, thereby allowing recolonisation of the oral cavity. The present
      study has also shown that either EK or IR-PCR is a useful typing approach in such
      epidemiological investigations.

PMID- 11302240
TI  - Epidemiological survey of oral submucous fibrosis and leukoplakia in aborigines
      of Taiwan.
AB  - A population-based survey was designed to investigate the prevalence of
      areca/betel quid chewing, oral submucous fibrosis and leukoplakia in a typical
      aboriginal community of southern Taiwan. Three hundred and twelve people 20 years
      of age or older were collected in the study. The prevalence of chewing
      areca/betel quid was 69.5%, with an average of 17.3 portions a day for an average
      24.4 years. More women (78.7%) than men (60.6%) chewed areca/betel quid. The
      prevalences of oral submucous fibrosis and leukoplakia were 17.6% and 24.4%,
      respectively. It was found that the odds ratio for chewing areca/betel quid and
      having at least one of the above oral mucosal lesions was 8.21. Any additional
      smoking or drinking habits were not significant for having oral mucosal lesions.
      Although the areca/betel quid in Taiwan does not contain any tobacco, a
      significant association was still identified between areca/betel quid chewing and
      oral mucosal lesions.

PMID- 11302241
TI  - Oral manifestations in HIV-positive adults from Northern Thailand.
AB  - Eighty-seven HIV-infected patients in a provincial hospital in Northern Thailand
      were examined for oral manifestations of HIV disease and AIDS. The median age was
      31.3 years. Seventy-four of the patients were women, 13 were men. 96.6% had a
      history of heterosexual transmission. Sixty-one patients were CDC-category A, 20
      were category B and 6 were category C (AIDS). Thirty-eight percent of the
      patients revealed oral lesions; 23% had one oral lesion and 13.8% had two oral
      lesions. Common lesions were oral candidiasis (10.3% pseudomembranous
      candidiasis, 6.9% erythematous candidiasis and 3.4% both forms), oral hairy
      leukoplakia (11.5%) and exfoliative cheilitis (6.9%). Gingival linear erythema
      was seen in 8% of the patients; periodontal lesions and necrotising ulcerative
      gingivitis were not observed. Men were more commonly affected by oral
      manifestations than women (P < 0.004). The spectrum of oral lesions is comparable
      to other studies from the region, although most of these reported more men than
      women. Also, the degree of immunosuppression was more marked (AIDS).

PMID- 11302242
TI  - Risk factors associated with oral lesions in HIV-infected heterosexual people and
      intravenous drug users in Thailand.
AB  - This study aimed to identify factors associated with the presence of oral lesions
      in HIV-infected individuals in Thailand, to determine the influence of gender and
      route of HIV transmission on the prevalence of the lesions, and to investigate
      whether total lymphocyte cell counts can be used as a serologic marker to predict
      the occurrence of oral lesions. Two hundred and seventy-eight HIV-infected
      heterosexual persons and intravenous drug users (IVDUs) were enrolled (230 males,
      48 females). Eighty-six HIV-free subjects from the same population were included
      as controls (61 males, 25 females). Oral candidiasis was the most common oral
      lesion among HIV-infected individuals (39.6%), followed by hairy leukoplakia (HL)
      (26.3%), exfoliative cheilitis (18.3%), and linear gingival erythema (LGE)
      (11.5%). Odds ratios (ORs) for factors associated with the presence of oral
      lesions were as follows for advanced HIV disease defined by clinical status:
      symptomatic stage [OR= 18.6; 95% confidence interval (CI) 7.3-47.2], AIDS stage
      [OR 7.3; 95% CI 3.4-15.7] and laboratory investigation of total number of
      lymphocyte cell counts of 1,000-2,000 cell/mm3 [OR 2.7; 95% CI 1.4-5.1] and
      <1,000 cell/mm3 [OR 4.0; 95% CI 2.3-7.0], alcohol consumption [OR 3.4; 95% CI 1.3
      9.1], and poor oral health [OR 1.7; 95% CI 1.0-2.9]. Men were significantly more
      likely to have oral lesions than women. No statistically significant difference
      in the presence of oral lesions was observed between heterosexuals and IVDUs.
      This study should help predict the risk of acquiring various types of oral
      lesions, given that the person is exposed to multiple risk factors compared to
      another who is not exposed to these factors.

PMID- 11302243
TI  - Telomerase activity and telomerase reverse transciptase (TERT) expression in
      ameloblastomas.
AB  - Telomerase activity is believed to be crucial for cell immortalization and
      cancerization, and is proven to be induced by c-myc protein. Telomerase reverse
      transcriptase (TERT) has been recently identified as a catalytic subunit of
      telomerase, whose expression is closely correlated with telomerase activity. We
      estimated telomerase activity by the telomeric repeat amplification protocol
      (TRAP) assay and examined the immunohistochemical expression of TERT and c-myc
      protein in 21 ameloblastoma tissues. All ameloblastoma samples were positive for
      telomerase activity, and TERT expression was detected in the nuclei of neoplastic
      cells but not in those of stromal cells. Numerous peripheral columnar or cuboidal
      cells, sporadic central polyhedral cells and some granular cells in
      ameloblastomas reacted with anti-TERT antibody. These results suggest that
      telomerase activity is associated with the oncogenesis or proliferative potential
      of odontogenic epithelium. The expression of c-myc protein showed a similar
      distribution pattern to that of TERT, suggesting that c-myc protein might induce
      telomerase activity in ameloblastomas.

PMID- 11302244
TI  - Adenomatoid odontogenic tumour: immunohistochemical demonstration of transferrin,
      ferritin and alpha-one-antitrypsin.
AB  - Three cases of adenomatoid odontogenic tumour (AOT) were examined by
      morphological and immunohistochemical methods, to define the nature of tumour
      cells and to determine the correlation between the occurrence of extracellular
      eosinophilic amorphous material and epithelial tumour cells. The epithelial
      tumour cell components observed in this study were divided into three cell types
      (cell type I: small compact cells in a solid nodule and pseudoglandular cells in
      a duct-like structure; cell type II: peripheral elongated cells and spindle
      shaped cells in a cribriform pattern; and cell type III: metaplastic squamous
      cells). The mesenchymal components consisted of eosinophilic amorphous material
      and calcified material. Immunohistochemically, the type I cells reacted
      positively with antibodies to transferrin, ferritin and alpha-one-antitrypsin
      (alpha1-AT), whereas the type II cells constantly indicated intense expression
      only for transferrin and alpha1-AT. All types of epithelial tumour cells reacted
      negatively with lactoferrin, alpha-one-antichymotrypsin, S-100 protein, S
      100alpha subunit and S-100beta subunit. Moreover, the eosinophilic amorphous
      material and calcified material examined were positive for the antibody against
      alpha1-AT. These materials expressed immunophenotypes similar to those of the
      epithelial tumour cells, except for metaplastic squamous cells. The present study
      showed that iron-binding proteins and proteinase inhibitor might be related to
      the pathogenesis of AOT. Furthermore, we indicated that the formation of
      eosinophilic amorphous material was associated with type I and type II cells.

PMID- 11302245
TI  - Immunohistochemical and ultrastructural investigation of apoptotic cell death in
      granular cell ameloblastoma.
AB  - Apoptotic cell death in granular cell ameloblastomas was examined by
      immunohistochemistry using anti-single-stranded DNA (ssDNA) antibody and
      transmission electron microscopy. Routinely prepared sections of granular cell
      ameloblastomas showed various quantities of granular cells with some apoptotic
      nuclear fragments. Immunoreactivity for ssDNA was higher in granular cells than
      in other neoplastic cells. Ultrastructural examination revealed abundant
      lysosomes in the cytoplasm of granular cells. Numerous apoptotic cell fragments
      with condensed nuclei in granular cell clusters were phagocytosed by adjacent
      granular cells. On immunohistochemical characterization of cellular
      differentiation, granular cells were positive for cytokeratin, CD68, lysozyme and
      alpha-1-antichymotrypsin, but negative for vimentin, desmin, S-100 protein,
      neuron-specific enolase and CD15, indicating epithelial origin and lysosomal
      aggregation. These features suggest that the cytoplasmic granularity in granular
      cell ameloblastomas might be caused by increased apoptotic cell death of
      neoplastic cells and associated phagocytosis by neighboring neoplastic cells.

PMID- 11302246
TI  - Atypical plexiform ameloblastoma with dentinoid: adenoid ameloblastoma with
      dentinoid.
AB  - In this study, we report a tumor that resembled previously reported uncommon
      tumors histologically similar to ameloblastoma or adenomatoid odontogenic tumor
      (AOT), showing the formation of hard tissue. We evaluated the histological
      characteristics by reviewing the literature. The patient was a 19-year old male.
      The lesion was located from the canine to third molar in the right mandible and
      was unicystic with a comparatively clear demarcation. The tumor tissue was cystic
      overall, showing multiple formation of small and large cysts. The tumor tissue
      resembled a variant form of plexiform ameloblastoma. Formation of dentin and
      dentinoid was observed in the tumor stroma, whereas formation of enamel was not
      observed. Very few cases of a variant form of ameloblastoma that shows formation
      of dentinoid have been reported, and the histological picture in this study
      closely resembled previously reported "adenoid ameloblastoma with dentinoid".

PMID- 11302247
TI  - The man behind the eponym--Paul Langerhans.

PMID- 11302248
TI  - Use of horizontal ultrathin gel electrophoresis to analyze allelic deletions in
      chromosome band 11p15.5 in gliomas.
AB  - The prognosis for most patients with astrocytic glioma is poor, and postoperative
      life expectancy has not significantly improved in the last decade despite
      advances in diagnosis, surgery, and adjuvant therapy. Progress has been made,
      however, in cataloging the genetic alterations that occur in these tumors.
      Studying the allelic changes using loss of heterozygosity analysis has proven to
      be a reliable and rapid way of identifying genetic alterations fundamental to the
      pathology of this disease. In this study, we used a series of fluorescent-labeled
      markers and a new horizontal ultrathin gel electrophoresis technology (HUGE;
      GeneSys Technologies, Inc.) to analyze loss of heterozygosity on 11p15 in a
      series of 24 matched normal/tumor glioma pairs that included both anaplastic
      astrocytomas and glioblastomas. These studies significantly narrowed the region
      harboring a putative 11p15.5 glioma-associated gene and further suggest that a
      second gene involved in the pathogenesis of brain tumors may exist, centromeric,
      in bands 11p15.5-p15.4.

PMID- 11302249
TI  - Overexpression of E2F1 in glioma-derived cell lines induces a p53-independent
      apoptosis that is further enhanced by ionizing radiation.
AB  - Glioma cell lines show variable responses to radiation in a manner influenced by
      their p53 status. Irradiation of glioma cell lines does not generally induce
      apoptosis. When wild-type p53 is present, these cells undergo a G1 arrest that is
      closely associated with increased radiosensitivity as measured by clonogenic
      survival. Previously, others have shown that dysregulated overexpression of E2F1
      induces apoptosis in cell lines with either functional or inactivated p53. We
      found that regardless of p53 status, apoptosis induced by overexpression of E2F1
      in glioma cell lines was further enhanced by treatment with ionizing radiation.
      BAX induction did not follow E2F1 overexpression or irradiation in the glioma
      cell lines tested. Thus, the apoptotic response of glioma-derived cells to
      irradiation can be enhanced by E2F1 by a mechanism that does not involve the
      induction of BAX.

PMID- 11302250
TI  - Phase II study of 6-thioguanine, procarbazine, dibromodulcitol, lomustine, and
      vincristine chemotherapy with radiotherapy for treating malignant glioma in
      children.
AB  - We conducted a single-arm phase II study to evaluate the efficacy and safety of
      radiotherapy combined with 6-thioguanine, procarbazine, dibromodulcitol,
      lomustine, and vincristine (TPDCV) chemotherapy for treating malignant
      astrocytoma in children and anaplastic ependymoma in patients of all ages.
      Between 1984 and 1992, 42 patients who had malignant astrocytomas (glioblastomas
      multiforme, anaplastic astrocytomas, or mixed anaplastic oligoastrocytomas) were
      treated with TPDCV chemotherapy and radiation therapy. Of these patients, 40 were
      younger than 18 years, but 2 were older (22 and 23 years) when treated. Cranial
      radiation averaged 58 Gy. TPDCV chemotherapy was given for 1 year or until
      progression. Between 1989 and 1991, 17 patients with malignant ependymoma were
      treated with TPDCV chemotherapy and craniospinal radiation. Radiation was given
      at an average dose of 54 Gy to the tumor, 28 Gy to the whole brain, and 31 Gy to
      the spinal axis. TPDCV chemotherapy was given for 1 year or until tumor
      progressed. Of the patients with glioblastoma multiforme, 13 of 17 died; the
      median time to progression was 49 weeks, and median survival was 85 weeks. The
      four patients surviving at this writing were followed a median 537 weeks (range
      364-635 weeks). Of the patients with nonglioblastoma malignant astrocytoma, 14 of
      25 died; the median time to progression was 224 weeks. Median survival was not
      reached in this group. The median follow-up for those surviving was 494 weeks.
      For the patients with ependymoma, 11 of 17 died with a median time to progression
      of 141 weeks. The median follow-up for the eight who survive was 469 weeks. Nine
      patients died with a median survival of 183 weeks. The combination of TPDCV and
      radiotherapy has activity against childhood anaplastic astrocytoma, glioblastoma
      multiforme, and anaplastic ependymoma. The results of this study for children
      with glioblastoma were comparable to results in the literature, while the results
      for children with anaplastic astrocytoma appeared better than most reports. The
      combination of TPDCV chemotherapy and radiation therapy for anaplastic
      ependymomas appears to be active and at least as good as published reports using
      radiation therapy alone.

PMID- 11302251
TI  - Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed
      glioblastoma multiforme and recurrent high-grade astrocytoma. NABTT CNS
      Consortium.
AB  - 9-Aminocamptothecin (9-AC) was administered as a 72-h i.v. infusion every 2 weeks
      to a total of 99 adults with high-grade astrocytomas. Fifty-one patients with
      newly diagnosed glioblastoma multiforme received 9-AC treatment prior to
      radiation therapy and 48 patients with high-grade astrocytomas were treated at
      the time of tumor recurrence. Upon entrance into these research protocols, all
      patients had measurable disease that was evaluated on a monthly basis with
      volumetric CT or MRI scans. A partial response was defined by > or =50% reduction
      in the contrast enhancing volume on stable or decreasing doses of
      glucocorticoids. The study specified that all apparent responders would have
      central review of their radiologic studies and histopathology. The initial
      patients treated with 9-AC were also receiving anticonvulsants and were noted to
      have minimal myelosuppression with this chemotherapy. Thus, 9-AC doses were
      escalated from the previously reported maximum tolerated dose (MTD) of 850
      microg/m2/24 h. We then established new MTDs for patients receiving enzyme
      inducing anticonvulsants. We defined these MTDs to be 1,776 microg/m2/24 h for
      newly diagnosed, previously untreated patients and 1,611 microg/m2/24 h for
      patients with recurrent disease. Twenty-two patients with newly diagnosed
      glioblastoma multiforme received 9-AC at doses > or =1,776 microg/m2/24 h. Of
      these, 18 had evaluable disease on central review, and 0 of 18 (0%) demonstrated
      a partial or complete response. Twenty-one patients with recurrent high-grade
      astrocytomas were treated at 1,611 microg/m2/24 h; 20 had evaluable disease and 0
      of 20 (0%) had a partial or complete response. Thus, the overall response rate in
      the 38 evaluable patients treated at the MTD was 0 of 38 (0%). Furthermore, of
      the 51 evaluable patients who were treated at doses less than the MTD, only one
      partial response was observed, yielding an overall response rate of 2%. Evidence
      of drug failure was rapid with tumor progression in one-half of patients after 2
      drug cycles. 9-AC lacks evidence of substantial activity in patients with newly
      diagnosed or recurrent high-grade astrocytomas.

PMID- 11302252
TI  - A phase I trial of 1,3-bis(2-chloroethyl)-1-nitrosourea plus temozolomide: a
      North American Brain Tumor Consortium study.
AB  - The North American Brain Tumor Consortium conducted a phase I trial of the
      combination 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide.
      Eligibility included a patient with a cancer type that was considered refractory
      to standard therapy. Prior nitrosourea treatments were not permitted. There were
      parallel dose escalations in two treatment schedules. Forty-five patients were
      enrolled during an 18-month period. The maximum tolerated doses (MTDs) when
      temozolomide followed BCNU (Arm A) were temozolomide at 550 mg/m2/p.o. and BCNU
      at 150 mg/m2/i.v.), whereas the MTD when temozolomide preceded BCNU (Arm B) was
      temozolomide at 400 mg/m2/p.o. and BCNU at 100 mg/m2/i.v. Toxicity was
      predominantly hematologic, although there were three instances of pulmonary
      toxicity, which in one case could have represented potentiation of nitrosourea
      induced pulmonary fibrosis. The half-life of temozolomide was 1.86 (+/-0.31) h.
      There was a moderate relationship between dose and peak concentration and a
      strong relationship between dose and plasma concentration time curve.
      Pharmacokinetic parameters of temozolomide were unaffected by the treatment
      schedule, so the difference in MTD between the schedules is likely due to a
      biologic rather than a pharmacokinetic sequence interaction. There were 9 partial
      responses among 43 patients evaluable for response, including 5 of 25 with a
      histologic diagnosis of glioblastoma. The recommended dose and schedule for phase
      II trials of this regimen are BCNU 150 mg/m2/i.v. followed in 2 h by temozolomide
      550 mg/m2/p.o. repeated every 6 weeks. We are also recommending screening and
      periodic pulmonary function testing during treatment to assess the possible
      potentiation of nitrosourea-induced pulmonary fibrosis.

PMID- 11302253
TI  - High-dose methotrexate for primary CNS lymphoma in the elderly.
AB  - Primary central nervous system lymphoma (PCNSL) in the immunocompetent patient
      reaches a peak incidence in the sixth and seventh decades of life. This
      retrospective study reviewed the efficacy and tolerability of high-dose
      methotrexate (HDMTX) in an elderly patient population. Between May 1995 and
      September 1998, ten consecutive elderly patients with histologically proven PCNSL
      were treated with HDMTX. The median age was 72.5 years and eight patients (80%)
      were older than 70 years. HDMTX was well tolerated with no episodes of grade 4
      toxicity nor febrile neutropenia. Toxicity included grade 3 nausea (1), grade 2
      mucositis (2), and grade 2 asymptomatic elevation of liver transaminases (2).
      Grade 1 toxicity occurred in three patients with nausea, diarrhea, and mild
      reversible elevation in serum creatinine in one patient each. Six patients had a
      complete response and three patients achieved a partial response, giving an
      overall response rate of 90% (95% confidence interval, 56%-100%). The median
      overall survival for the cohort was 36 months (range 4-43 months). In summary,
      HDMTX is well tolerated in this elderly population with PCNSL and achieves
      response rates and median survival comparable with other chemotherapy or
      radiotherapy regimens.

PMID- 11302254
TI  - The blood-brain and blood-tumor barriers: a review of strategies for increasing
      drug delivery.
AB  - Drug delivery to brain tumors has been a controversial subject. Some believe the
      blood-brain barrier is not important, while others believe it is the major
      obstacle in treatment and have devised innovative approaches to circumvent it.
      These approaches can be divided into two categories: those that attempt to
      increase drug delivery of intravascularly administered drugs by manipulating
      either the drugs or capillary permeability, and those that attempt to increase
      drug delivery by local administration. Several strategies have been developed to
      increase the fraction of intravascular drug reaching the tumor, including intra
      arterial administration, barrier disruption, new ways of packaging drugs, and,
      most recently, inhibiting drug efflux from tumor. When given intravascularly, all
      drugs have a common drawback: the body acts as a sink, and, even in the best
      situations, only a small fraction of administered drug actually reaches the
      tumor. A consequence is that systemic toxicity is usually the dose-limiting
      factor. When given locally, such as into the cerebrospinal fluid or directly into
      the tumor, 100% of an administered dose is delivered to the target site. However,
      local delivery is associated with variable and unpredictable spatial distribution
      and variation in drug concentration. The major dose-limiting factor of most local
      delivery methods will be neurotoxicity. The relative advantages and disadvantages
      of the different methods of circumventing the blood-brain barrier are presented
      in this review, and special attention is given to convection-enhanced delivery,
      which has particular promise for the local delivery of large therapeutic agents
      such as monoclonal antibodies, antisense oligonucleotides, or viral vectors.

PMID- 11302256
TI  - The use of ionising radiations in medicine. A new era?

PMID- 11302255
TI  - SETA: a novel SH3 domain-containing adapter molecule associated with malignancy
      in astrocytes.
AB  - Differential display polymerase chain reaction analysis was used to compare five
      differentiation states of the O-2A progenitor-like cell line CG4: progenitor
      cells and cells at 12 h or 4 days after the induction of differentiation into
      oligodendrocytes or astrocytes. This led to the identification of 52 sequence
      tags that were expressed differentially with cellular phenotype. One sequence was
      upregulated during differentiation of CG4 cells and represented a novel gene that
      we named SETA (SH3 domain-containing gene expressed in tumorigenic astrocytes).
      This gene encodes an SH3 domain-containing adapter protein with sequence
      similarity to the CD2AP (CD2 adapter protein) and CMS (Cas ligand with multiple
      Src homology) genes. SETA mRNA was expressed at high levels in the developing rat
      brain but was barely detectable in the normal adult rat or human brain. However,
      SETA mRNA was found in approximately one half of the human gliomas tested,
      including astrocytomas grades II, III, and IV, as well as oligodendrogliomas,
      mixed oligoastrocytomas, and human glioma-derived cell lines. A rat glioma
      generated by treatment with the alkylating carcinogen ethylnitrosourea on
      postnatal day 1 and a derived cell line also expressed SETA mRNA. Furthermore, in
      an in vitro model of astrocytoma progression based on p53-/- astrocytes,
      expression of SETA was restricted to cells that are tumorigenic.

PMID- 11302257
TI  - Implications of ICRP 60 and the patient directive 97/43 Euratom for nuclear
      medicine.
AB  - The Council of the European Union has completely renewed the framework regarding
      radiation protection by adopting 2 directives: Directive 97/43 Euratom lays down
      the general principles of the radiation protection of individuals undergoing
      exposure to ionizing radiations related to medical exposures, as a supplement of
      Directive 96/29 Euratom laying down the basic safety standards for the protection
      of the health of workers and the general public against the dangers arising from
      ionizing radiations. Member States shall bring into force the laws, regulations
      and administrative provisions necessary to comply with these two directives
      before 13 May 2000. Since medical applications represent the largest man-made
      sources of radiation exposure for the European population and exposure to low
      levels of ionizing radiations has become a sensitive issue for the public, the
      nuclear medicine community is concerned by the set of European legislation which
      appear to be more restrictive than the previous one. It is based on the
      scientific knowledge concerning radiation protection as expressed in particular
      in Recommendation No. 60 of the International Commission on Radiological
      Protection. In this paper, the directives are carefully analyzed and evaluated in
      terms of their potential impact on nuclear medicine practice.

PMID- 11302258
TI  - Naturally occurring radioactive materials (NORM): a matter of wide societal
      implication.
AB  - Naturally occurring radioactive materials are ubiquitous on Earth and their
      radioactivity may become concentrated as a result of human activities. Numerous
      industries produce concentrated radioactivity in their by-products: the coal
      industry, petroleum extraction and processing, water treatment, etc. The present
      reference system of radiation protection does not provide a complete framework
      for the coherent management of all types of radioactively contaminated materials.
      Inconsistencies in waste management policy and practice can be noted across the
      board, and especially vis-a-vis the management of radioactive waste from the
      nuclear industry. This article reviews the present societal approach to manage
      materials that are radioactive but are often not recognised as being such, and
      place the management of radioactive materials from the nuclear industry in
      perspective.

PMID- 11302259
TI  - Radiation and pregnancy.
AB  - Irradiation of pregnant women either in the workplace or as a consequence of
      clinical diagnosis is often unavoidable. This paper reviews the issues relating
      to this topic. For clinical exposures the "missed period" rule is applied prior
      to most clinical studies. However normal physiological variations in the
      menstrual cycle may need to be understood. The possible effects of irradiation,
      both deterministic and stochastic, on the fetus are also described. The decision
      process in relation to irradiation of a pregnant or potentially pregnant patient
      is discussed in terms of the regulatory guidance. A different approach is needed
      for studies which clearly involve a low dose to the uterus compared with studies
      involving a high dose, including therapy. The issue of a pregnant or potentially
      pregnant worker in nuclear medicine is also considered. Restrictions on certain
      work activities may be necessary once pregnancy is declared. Other areas
      considered are biomedical research and also the potential for exposure of
      pregnant woman in the home or in the workplace as a consequence of others having
      a nuclear medicine study.

PMID- 11302260
TI  - Dosimetry in radionuclide therapies with 90Y-conjugates: the IEO experience.
AB  - The basis for a successful radionuclide therapy is a high and stable uptake of
      the radiopharmaceutical in the target tissue along with low activity
      concentration in other normal organs. The contribution of dosimetry in
      radionuclide therapy is to predict before the treatment the absorbed doses in
      tumor and normal organs, to identify the critical organs, to minimize any
      possible toxicity and to evaluate the maximum tolerated dose. We report our
      experience concerning pharmacokinetics and dosimetry of two 90Y-therapeutic
      protocols: 3-step pretargeting radioimmunotherapy (RIT) according to the biotin
      avidin system and receptor mediated radionuclide therapy with the somatostatin
      analogue [DOTA-D-Phe1-Tyr3] octreotide named DOTATOC. For the dosimetric
      analysis, analogous approaches for the two radiolabeled compounds due to the
      similar pharmacokinetic characteristics were adopted; the MIRD formalism was
      applied, taking into account both the physical and the biological characteristics
      of the radioconjugate and patients' metabolism. In order to determine biological
      clearance, serial blood samples and complete urine collection were obtained up to
      48 hours after injection; to evaluate biodistribution, several whole body scans
      were acquired. Both therapies showed the advantageous characteristics of a fast
      blood clearance and a predominantly renal excretion of the radiopharmaceuticals
      thus lowering the irradiation of the total body. Although pharmacokinetic
      characteristis were similar, different critical organs were found for the two
      therapies; in particular, some considerations regarding red marrow, spleen and
      kidneys were required. The results of our studies indicate that high activities
      of 90Y-biotin (3-step RIT) and 90Y-DOTATOC can be administered with acceptable
      radiation doses to normal organs.

PMID- 11302261
TI  - Health effects of therapeutic use of 131I in hyperthyroidism.
AB  - Since 1942, therapy with radioiodine (Na131I) has gained a major role in the
      treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves'
      disease or toxic multinodular goiter. The very large series of patients treated
      so far offer the opportunity for an assessment of both benign and malignant side
      effects. Hyperthyroidism is sometimes observed after radioiodine therapy due to
      radiation induced thyroid hormone or by an immunological mechanism. Despite the
      numerous attempts to design dosage schedules aiming at euthyroidism,
      hypothyroidism occurs in the majority of patients throughout life. Transient
      hypothyroidism may be observed within the first year after therapy and is caused
      by an immunological mechanism. Radioiodine therapy in Graves' disease may induce
      or worsen ophthalmopathy, which can be prevented by steroids effectively.
      Hypoparathyroidism and hyperparathyroidism have been reported after radioiodine
      therapy but probably do not exceed the normal incidence. Sialitis is commonly
      observed but mostly in patients treated with radioiodine for thyroid cancer.
      There are no indications for induction of genetic abnormalities after radioiodine
      therapy although no definite conclusion can be reached. Much attention has been
      paid to malignant disease. In very large series, no effects of radioiodine
      therapy on survival have been observed. Some studies report an increased relative
      risk for certain types of cancer (notably thyroid cancer, stomach cancer, bladder
      and kidney cancer or hematological malignancies). However, these observations
      were not confirmed by other large studies, so that no definite conclusion with
      respect to risk for certain types of malignant disease can be drawn. However,
      radioiodine therapy for benign thyroid disorders has generally been considered
      safe and without major side effects, hypothyroidism being the most frequent one.

PMID- 11302262
TI  - Radiation exposure and dosimetry in transplant patients due to nuclear medicine
      studies.
AB  - Organ transplantation is now an accepted method of therapy for treating patients
      with end stage failure of kidneys, liver, heart or lung. Nuclear Medicine may
      provide functional data and semi-quantitative parameters. However, one serious
      factor that hampers the use of nuclear medicine procedures in transplant patients
      is the general clinical concern about radiation exposure to the patient. This
      leads us to discuss the effective doses and radiation dosimetry associated with
      radionuclide procedures used in the management and follow-up of transplant
      patients. A simple way to place the risk associated with Nuclear Medicine studies
      in an appropriate context is to compare the dose with that received from a more
      familiar source of exposure such as from a diagnostic X-ray procedure. The
      radiation dose for the different radiopharmaceuticals used to study transplant
      organ function ranges between 0.1 and 5.3 mSv which is comparable to X-ray
      procedures with the exception of 201Tl and 111In-antimyosin. Thus Nuclear
      Medicine studies do not bear a higher radiation risk than the often used X-ray
      studies in transplant patients.

PMID- 11302263
TI  - Genetic susceptibility to radiations. Which impact on medical practice?
AB  - Recent progress especially in the field of gene identification and expression
      have raised more attention on genetic susceptibility to cancer possibly enhanced
      by radiation. Radiation therapists are mostly concerned by this question since
      hypersensitive patients may suffer from adverse effects in normal tissues
      following a standard radiation therapy and normally sensitive patients could
      benefit from higher doses of radiation for better treatment of their malignant
      tumors. Although only a small percentage of individuals are "hypersensitive" to
      radiation effects, all medical specialists using ionising radiation should be
      aware of this new progress in medical knowledge. The present paper reviews the
      main pathologies (diseases, syndromes...) known or strongly suspected to be
      associated with a hypersensitivity to ionizing radiation. Then the main tests
      capable of detecting in advance such pathologies are analyzed and compared.
      Finally guidelines are provided, especially to the radiation therapists to limit
      the risk of severe complications (or even deaths) for this specific subset of
      patients suffering from a genetic disorder with a susceptibility to radiations.

PMID- 11302264
TI  - Radiosensitivity of tumor cells. Oncogenes and apoptosis.
AB  - The success of treatment of cancer patients by radiotherapy largely depends on
      tumor radiosensitivity. Several molecular factors that determine the sensitivity
      of tumor cells to ionizing radiation have been identified during the last couple
      of years. Some of these factors are known as oncogenes and tumor suppressor
      genes. This review focuses on the influence of some of these molecular factors on
      a major determinant of radiosensitivity: i.e. programmed cell death or apoptosis.
      The crucial molecular step in ionizing radiation-induced apoptosis is the release
      of mitochondrial cytochrome c into the cell's cytosol. The ways the tumor
      suppressor protein p53, as well as the oncogenes ras and raf, c-myc and Bcl-2 can
      influence this process at different stages are presented. As will be discussed,
      the result of activation of an oncoprotein on tumor radiosensitivity depends on
      its mechanism of action and on the presence of other (oncogenic) factors, since
      complex interactions among many molecular factors determine the delicate balance
      between cell proliferation and cell death. The ongoing identification and
      characterization of factors influencing apoptosis will eventually make it
      possible to predict tumor radiosensitivity and thereby improve cancer treatment.

PMID- 11302265
TI  - Interpersonal processes and psychopathology among expectant and nonexpectant
      adolescent couples.
AB  - This study examined the interpersonal and psychological functioning of expectant
      and nonexpectant adolescent couples. Interpersonal processes were assessed using
      the Structural Analysis of Social Behavior (L. S. Benjamin, 1974) and
      psychological functioning was assessed using the Diagnostic Interview for
      Children and Adolescents--Revised (W. Reich, 1991). Compared with their
      nonexpectant peers, expectant couples exhibited higher rates of negative
      interpersonal processes, including demand-withdraw behaviors and lower rates of
      positive interpersonal processes. Expectant males reported higher rates of
      behavior disorders, substance use disorders, and internalizing disorders than
      nonexpectant males. Higher rates of substance-use disorders mediated the effect
      of expectancy status on demand-withdraw behavior. Results help clarify the links
      between the psychological risks associated with adolescent pregnancy and the
      interpersonal functioning of young expectant couples.

PMID- 11302266
TI  - The investigation of exposure and cognitive therapy: comment on Tarrier et al
      (1999).
AB  - This article outlines concerns relating to the N. Tarrier et al. (1999)
      investigation comparing imaginal exposure and cognitive therapy. Specifically,
      the authors offer N. Tarrier et al. the opportunity to operationally define and
      clarify the claim that more patients treated by imaginal exposure "worsened"
      during treatment. Equally, in light of N. Tarrier et al.'s low effect sizes in
      relation to past research the authors also highlight the need to utilize
      accountable treatment integrity checks.

PMID- 11302269
TI  - Marital adjustment and outcome following treatments for depression.
AB  - Marital adjustment and treatment outcome were evaluated in the Treatment of
      Depression Collaborative Research Program, a multicenter clinical trial
      evaluating interpersonal psychotherapy, cognitive therapy, imipramine, and
      placebo. Marital adjustment and depression were assessed pre- and posttreatment,
      and depression was assessed at 6, 12, and 18 months after treatment. Results
      indicate that (a) there was a significant improvement in marital adjustment after
      treatment, (b) this effect was not moderated by treatment type, and (c) this
      effect was mediated by change in depression. Poor pretreatment marital adjustment
      was modestly associated with negative outcome, whereas poor posttreatment marital
      adjustment was strongly associated with negative outcome during follow-up. The
      findings suggest that poor marital adjustment at the end of active treatment is a
      risk factor for increases in depression severity during follow-up.

PMID- 11302268
TI  - Therapeutic alliance as a predictor of outcome and retention in the National
      Institute on Drug Abuse Collaborative Cocaine Treatment Study.
AB  - The authors examined the relation between therapeutic alliance, retention, and
      outcome for 308 cocaine-dependent outpatients participating in the National
      Institute on Drug Abuse Collaborative Cocaine Treatment Study. High levels of
      alliance were observed in supportive-expressive therapy (SE), cognitive therapy
      (CT), and individual drug counseling (IDC), and alliance levels increased
      slightly but significantly from Session 2 to Session 5 in all groups. In contrast
      to other studies, alliance was not a significant predictor of drug outcome.
      However, alliance did predict patient retention differentially across the 3
      treatments. In SE and IDC, either higher levels of alliance were associated with
      increased retention or no relationship between alliance and retention was found,
      depending on the time alliance was measured. In CT, higher levels of alliance
      were associated with decreased retention.

PMID- 11302270
TI  - Young adults' immediate and delayed reactions to simulated marital conflicts:
      implications for intergenerational patterns of violence in intimate
      relationships.
AB  - This study investigated the thoughts and feelings that young adults from violent
      (VPA) and nonviolent (NPA) interparental-conflict backgrounds reported while
      listening to simulated marital conflicts and after a delay for reflection. While
      listening to conflicts, VPAs were more likely than NPAs to predict negative
      outcomes and to place blame. No between-groups differences regarding negative
      outcomes emerged after a delay. VPAs also reported perpetrating and experiencing
      more aggressive conflict in their dating relationships. Post hoc probes revealed
      that the negative-outcome-prediction and blaming variables played no significant
      mediating role in participants' intergenerational patterns of intimate
      relationship aggression; however, methodological limitations likely compromised
      the statistical power for examining this mediational model. Results are discussed
      in light of research regarding intergenerational patterns of violence within
      families.

PMID- 11302271
TI  - Discrepant substance use and marital functioning in newlywed couples.
AB  - The configuration of partners' drinking patterns may be most critical to marital
      functioning. Implications of discrepant husband and wife smoking, drinking, and
      drug use for relationship quality at the transition to marriage were examined.
      Participants were 642 couples entering into their 1st marriage. Separate, self
      administered questionnaires were completed at home by each partner. Both husbands
      and wives in couples in which only 1 partner drank heavily or used drugs reported
      significantly lower marital quality than other spouses. Husband Use x Wife Use
      interactions were not significant for cigarette use, alcohol use, or regular
      drinking. Discrepancies in more deviant substance use behaviors may be most
      relevant to marital functioning.

PMID- 11302272
TI  - Cognitive-behavioral treatment of anxiety disorders in children: long-term (6
      year) follow-up.
AB  - Authors evaluated the long-term effectiveness of cognitive-behavioral therapy
      (CBT) for childhood anxiety disorders. Fifty-two clients (aged 14 to 21 years)
      who had completed treatment an average of 6.17 years earlier were reassessed
      using diagnostic interviews, clinician ratings, and self- and parent-report
      measures. Results indicated that 85.7% no longer fulfilled the diagnostic
      criteria for any anxiety disorder. On a majority of other measures, gains made at
      12-month follow-up were maintained. Furthermore, CBT and CBT plus family
      management were equally effective at long-term follow-up. These findings support
      the long-term clinical utility of CBT in treating children and adolescents
      suffering from anxiety disorders.

PMID- 11302273
TI  - Sexual revictimization prevention: an outcome evaluation.
AB  - This investigation tested a program to reduce women's risk for sexual
      revictimization. Participants were 66 women with histories of sexual
      victimization as adolescents or adults who were randomly assigned to a preventive
      intervention group or a no-treatment control group. They completed initial
      measures assessing history of sexual assault, self-efficacy, and psychological
      functioning, returning approximately 2 months later for follow-up assessment
      using the same measures. Results suggest that the prevention program may be
      effective in reducing the incidence of sexual assault revictimization in this
      population. In addition, participants in the intervention group displayed
      significant improvement in psychological adjustment and self-reported self
      efficacy.

PMID- 11302274
TI  - Family treatment and medication dosage reduction in schizophrenia: effects on
      patient social functioning, family attitudes, and burden.
AB  - The effects of 2 family intervention programs (supportive family management
      [SFM], including monthly support groups for 2 years; or applied family management
      [AFM], including 1 year of behavioral family therapy plus support groups for 2
      years), and 3 different neuroleptic dosage strategies (standard, low, targeted)
      on social functioning of patients with schizophrenia. their relatives' attitudes,
      and family burden were examined. AFM was associated with lower rejecting
      attitudes by relatives toward patients and less friction in the family perceived
      by patients. Patients in both AFM and SFM improved in social functioning but did
      not differ, whereas family burden was unchanged. Medication strategy had few
      effects, nor did it interact with family intervention. The addition of time
      limited behavioral family therapy to monthly support groups improved family
      atmosphere, but did not influence patient social functioning or family burden.

PMID- 11302275
TI  - Effectiveness of personalized written feedback through a mail intervention for
      smoking cessation: a randomized-controlled trial in Spanish smokers.
AB  - This study evaluated the effects of written feedback adapted to a self-help mail
      intervention. The efficacy of the standard mail intervention treatment was 37% at
      the end of treatment, 22% at the 3-month follow-up, 19% at the 6-month follow-up,
      and 13% at the 12-month follow-up. In contrast, the standard mail program
      combined with personalized written feedback resulted in an efficacy of 51% at the
      end of treatment, 37% at the 3-month follow-up, 32% at the 6-month follow-up, and
      27% at the 12-month follow-up. Both groups were significantly different from the
      control group at the end of treatment (0%), at the 3-month follow-up (1%), and at
      the 6-month follow-up (1%). There was a significant reduction in the number of
      cigarettes smoked daily among continuing smokers under both experimental
      conditions. The authors conclude that written feedback substantially increases
      abstinence rates when it is applied following similar guidelines to those used in
      clinical settings.

PMID- 11302276
TI  - Posttraumatic stress disorder and depression symptomatology in a sample of Gulf
      War veterans: a prospective analysis.
AB  - The authors examined the relationship over time of posttraumatic stress disorder
      (PTSD) and depression symptoms in a sample of Gulf War veterans. A large sample
      (N = 2,949) of Gulf War veterans was assessed immediately following their return
      from the Gulf region and 18-24 months later. Participants completed a number of
      self-report questionnaires including the Mississippi Scale for Combat-Related
      PTSD (T. M. Keane, J. M. Caddell, & K. L. Taylor, 1988) and the Brief Symptom
      Inventory (L. R. Derogatis & N. Melisaratos, 1983) at both time points and an
      extended and updated version of the Laufer Combat Scale (M. Gallops, R. S.
      Laufer, & T. Yager, 1981) at the initial assessment. A latent-variable, cross-lag
      panel model found evidence for a reciprocal relation between PTSD and Depression.
      Follow-up models examining reexperiencing, avoidance-numbing, and hyperarousal
      symptoms separately showed that for reexperiencing and avoidance-numbing
      symptoms, the overall reciprocal relation held. For hyperarousal symptoms,
      however, the association was from early hyperarousal to later depression symptoms
      only.

PMID- 11302277
TI  - Motivational enhancement and self-help treatments for problem gambling.
AB  - Two brief treatments for problem gambling were compared with a waiting-list
      control in a randomized trial. Eighty-four percent of participants (N = 102)
      reported a significant reduction in gambling over a 12-month follow-up period.
      Participants who received a motivational enhancement telephone intervention and a
      self-help workbook in the mail, but not those who received the workbook only, had
      better outcomes than participants in a 1-month waiting-list control. Participants
      who received the motivational interview and workbook showed better outcomes than
      those receiving the workbook only at 3- and 6-month follow-ups. At the 12-month
      follow-up, the advantage of the motivational interview and workbook condition was
      found only for participants with less severe gambling problems. Overall, these
      results support the effectiveness of a brief telephone and mail-based treatment
      for problem gambling.

PMID- 11302278
TI  - Predicting clinically significant response to cognitive behavior therapy for
      chronic insomnia in general medical practice: analysis of outcome data at 12
      months posttreatment.
AB  - The clinical efficacy of cognitive behavior therapy (CBT) for chronic insomnia
      has been established, yet clinical effectiveness is less clear. This study
      presents data on 109 patients from general practice during a formal evaluation of
      clinical effectiveness. Two thirds achieved normative values of < or =30 min for
      sleep latency and wakefulness during the night after CBT. Furthermore, almost
      half of the sample reduced sleeplessness by > or =50%. Logistic regression
      revealed that initial severity did not contraindicate good outcome. Rather,
      greater sleep disturbance was positively associated with large symptom reduction,
      although lower endpoint scores were less likely. Similarly, symptoms of anxiety,
      depression, and thinking errors positively predicted good outcome. Hypnotic using
      patients responded equally well to CBT, and demographic factors were of no
      significant predictive value. It is concluded that CBT is clinically and durably
      effective for persistent insomnia in routine practice.

PMID- 11302279
TI  - Effects of medication, behavioral, and combined treatments on parents' and
      children's attributions for the behavior of children with attention-deficit
      hyperactivity disorder.
AB  - Seventy-four mothers and 41 fathers and their 6 to 13 year old sons with
      attention-deficit hyperactivity disorder (ADHD) watched videos of child ADHD
      symptoms, compliance, and noncompliance. Participants were told either that the
      child was receiving medication, behavioral treatment, a combination of the two,
      or was not receiving treatment and were asked to rate the cause of the behavior.
      Parents attributed less control but greater stability to positive child behaviors
      when the child was receiving medication. However, for negative behaviors,
      medication increased attributions of control but diminished stability. With
      behavior management. compliance was seen as more external and stable and
      noncompliance as more controllable but less stable. For all treatments, boys
      reported increased control over ADHD symptoms and noncompliance. The implications
      of these treatment-related attributions for parenting and children's self
      perceptions are discussed.

PMID- 11302280
TI  - The relation of alcohol use to HIV-risk sexual behavior among adults with a
      severe and persistent mental illness.
AB  - The authors examined the relationship between alcohol use and HIV-risk sexual
      behavior and tested whether alcohol use immediately prior to sex is related to
      decreased condom use. The participants were 159 adults living with a severe and
      persistent mental illness. Each participated in a structured interview to assess
      all sexual and drug-use behavior over a 3-month period. Analysis of 3,026 sexual
      behaviors reported by 123 sexually active participants indicated that at the
      global level, participants who drank more heavily were more likely to have
      engaged in sexual risk behavior. At the event level, however, alcohol use was not
      related to condom use during vaginal or anal intercourse; that is, participants
      who used condoms when sober tended to use them to the same extent when drinking.

PMID- 11302281
TI  - The relation of daily stressors to somatic and emotional symptoms in children
      with and without recurrent abdominal pain.
AB  - Prior investigations of the relation between stressors and symptoms in children
      with recurrent abdominal pain (RAP) have focused on major negative life events.
      This study used consecutive daily telephone interviews to assess daily stressors
      and symptoms in 154 pediatric patients with RAP and 109 well children. Results
      showed that patients with RAP reported more frequent daily stressors than well
      children reported both at home and at school. Idiographic (within-subject)
      analyses indicated that the association between daily stressors and somatic
      symptoms was significantly stronger for patients with RAP than for well children.
      In contrast, the relation between daily stressors and negative affect did not
      differ between the groups. The relation between daily stressors and somatic
      symptoms was stronger for patients with RAP who had higher levels of trait
      negative affectivity.

PMID- 11302282
TI  - Changes in alcoholic patients' coping responses predict 12-month treatment
      outcomes.
AB  - Patient subtypes (Types A and B alcoholism), determinants, and outcomes
      associated with changes in coping responses of 133 alcoholic patients in the year
      following admission to treatment were examined. In general, patients' use of
      avoidance coping declined and use of approach coping increased. Type B patients
      used more avoidance coping than did Type A patients, but the subtypes did not
      differ in rate of change in coping. As a determinant of coping, cognitive
      appraisal of threat showed a trend toward predicting avoidance coping at 6- and
      12-month follow-ups. Decreased cognitive avoidance coping (e.g., daydreaming)
      predicted fewer alcohol, psychological, and interpersonal problems. Increased
      behavioral approach coping (e.g.. taking action) predicted lower severity of
      alcohol problems. Further study of changes in the cognitive aspects of coping
      (i.e., appraisals and cognitive avoidance coping) is needed to determine
      mechanisms underlying cognitive processes associated with treatment outcomes.

PMID- 11302283
TI  - Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial.
AB  - A number of trials and meta-analyses have demonstrated clear benefits of blood
      pressure (BP) reduction in patients aged <80 years with regard to the reduction
      in stroke and cardiovascular events. However, a variety of studies have suggested
      that the positive relationship between BP and cardiovascular mortality is
      weakened or indeed reversed in the very elderly. Most intervention trials to date
      have either excluded or not recruited sufficient patients aged > or =80 years to
      determine whether there is a significant benefit from treatment in this age
      group. A meta-analysis of intervention trials that recruited patients aged > or
      =80 years has suggested a benefit in terms of stroke reduction but has also
      raised the possibility of an increase in total mortality. The benefit to risk
      ratio therefore needs to be clearly established before recommendations can be
      made for treating very elderly patients with hypertension. The Hypertension in
      the Very Elderly Trial (HYVET) pilot recruited 1283 patients aged > or =80 years
      and showed the feasibility of performing such a trial in this age group. It was a
      Prospective Randomised Open Blinded End-Points (PROBE) design but the main trial
      has additional pharmaceutical sponsorship to run a double-blind trial. Therefore,
      the main trial is a randomised, double-blind, placebo-controlled trial designed
      to assess the benefits of treating very elderly patients with hypertension. It
      compares placebo with a low dose diuretic (indapamide sustained release 1.5mg
      daily) and additional ACE inhibitor (perindopril) therapy if required. As in the
      pilot trial, the primary end-point is stroke events (fatal and non-fatal) and the
      trial is designed to determine whether or not a 35% difference occurs between
      placebo and active treatment. The main objective will be achieved with 90% power
      at the 1% level of significance. Secondary outcome measures will include total
      mortality, cardiovascular mortality, cardiac mortality, stroke mortality and
      skeletal fracture. 2100 patients aged > or =80 years are to be recruited and
      followed up for an average of 5 years. Entry BP criteria after 2 months of a
      single-blind placebo run-in period are a sustained sitting systolic BP (SBP) of
      160 to 199mm Hg and a diastolic BP of 90 to 109mm Hg. The standing SBP must be
      >140mm Hg. The trial will be carried out in accordance with the principles of
      Good Clinical Practice. We describe in detail the protocol for the main trial and
      discuss the reasons for the changes from the pilot, the use of the drug regimen,
      and the BP criteria to be used in the trial.

PMID- 11302284
TI  - Parasitic skin infections in the elderly: recognition and drug treatment.
AB  - There are many parasitic infections of medical importance, which can produce both
      systemic disease as well as skin lesions. For the most part, treatment of these
      infections in the elderly does not differ very much from that of younger
      patients. However, one must be aware that the geriatric population can present
      with certain challenges with regard to diagnosis of these diseases because
      history taking may be more difficult and patients often already have a set of
      other medical problems, which may overshadow the skin lesions. In addition, the
      clinical manifestations of these infections may not appear classical and may be
      altered. Dosages of drugs used to treat these infections, even topical agents,
      may require adjustments in this population. The recognition of scabies in elderly
      people living together is important and early treatment with topical scabiecides,
      including oral ivermectin, will help to control the spread of the infestation.
      Pediculosis may be a cause of pruritus in the elderly and can be treated with
      malathione, lindane or permethrin. Less common parasitic infections in the
      elderly, including cutaneous larva migrans and cutaneous leishmaniasis, present
      with a characteristic clinical picture and can be effectively treated with oral
      thiabendazole and intravenous antimonials.

PMID- 11302285
TI  - Dyspnoea in the elderly: a clinical approach to diagnosis.
AB  - This review briefly overviews the pathophysiology of dyspnoea and then focuses on
      discussion of the most frequent causes of chronic and acute dyspnoea in the
      elderly. The most common causes of dyspnoea in the elderly include heart failure,
      chronic obstructive pulmonary disease and asthma. Other causes include
      parenchymal lung disease, pulmonary vascular diseases, upper airway obstruction
      and pneumonia. Dyspnoea should not be attributed to aging alone. Careful clinical
      evaluation and spirometry is indicated, and additional testing may be
      appropriate. In this article, emphasis is placed on the clinical manifestations
      of dyspnoea in the elderly and an approach to their differential diagnosis is
      provided. Discussion of available therapy is beyond the scope of this article.

PMID- 11302286
TI  - Antibacterial treatment of invasive mechanical ventilation-associated pneumonia.
AB  - Patients admitted to intensive care units (ICU) are at higher risk of acquiring
      nosocomial infections than patients in other hospital areas. This is the
      consequence of both a greater severity of illness with its implications
      (manipulation, invasiveness) and crossed infection from reservoirs inside the
      ICU. The most frequent nosocomial infection is invasive ventilation-associated
      pneumonia (VAP) which leads to an important increase in morbidity and mortality.
      The most important aetiological agents in VAP are bacteria, with a marked
      predominance of Staphylococcus aureus and Pseudomonas aeruginosa. These
      aetiologies may be different depending upon the type of ICU (medical, surgical,
      coronary) or the presence of certain risk factors (duration of mechanical
      ventilation before onset of pneumonia, previous exposure to antibacterials).
      Susceptibilities of the aetiological agents to antibacterials may also vary
      according to the type of ICU and over time. Data from global studies show an
      increase in multiresistant bacteria but these data may not be applied to a local
      ICU. The availability of accurate and updated information on the most frequently
      encountered organisms in each ICU and their susceptibilities is very important in
      order to provide the most adequate treatment. A controversial issue is the
      selection of antibacterials. According to the latest evidence the most adequate
      approach is a prompt administration of empirical treatment. Based on knowledge of
      bacterial flora in our own ICU, the choice of an adequate therapeutic regimen
      will decrease both morbidity and mortality. A second issue is monotherapy versus
      combined therapy. The most common recommendation, with a few exceptions, is to
      use combined therapy until microbiological results are received. Another
      controversy is the choice of antibacterials in the combined regimen. The most
      commonly recommended combination is that of a beta-lactam with an aminoglycoside,
      except in early-onset pneumonia without risk factors. The use of monotherapy with
      a cefalosporin without antipseudomonal activity or amoxicillin-clavulanic acid is
      the recommended regimen. Treatment should be modified based on microbiological
      results. There are no well documented recommendations on the prophylactic
      duration of treatment and it must be based on the aetiological agent and the
      clinical course. In summary treatment of VAP must be prompt, empirical and
      combined (beta-lactam plus aminoglycoside ). However, the choice of the
      antibacterial regimen should follow local guidelines of treatment based upon the
      knowledge of the most frequently isolated bacterial flora and their
      susceptibilities in different clinical settings.

PMID- 11302287
TI  - Drug treatment options for irritable bowel syndrome: managing for success.
AB  - Irritable bowel syndrome (IBS) is a functional gut disorder the diagnosis of
      which is based on clinical symptoms as set forth by the Rome criteria. As the
      population ages, especially with the population of patients >75 years of age
      expanding greatly over the next 10 years, IBS is becoming one of the most common
      diseases of the elderly. Thus far, developing treatment strategies for patients
      with IBS has been difficult because of the lack of pharmacological targets and
      the wide range of symptomatology. Additionally, demonstration of a therapeutic
      benefit is difficult in the presence of a high placebo response observed
      regardless of the therapy employed. Fibre, antidiarrhoeals and antispasmodics all
      play some role in the symptomatic treatment of IBS. With the evolution of IBS as
      a disorder of visceral hypersensitivity, new drugs have been developed that
      target the enteric nervous system. Tricyclic antidepressants (TCAs) have been
      found to target the enteric neurons and play a role in pain modulation.
      Currently, the TCAs are recommended only for severe cases of IBS pain. The newest
      class of drugs to be approved for use in IBS are the serotonin (5
      hydroxytryptamine; 5-HT) antagonists. Specifically, the 5-HT3 receptor
      antagonists have been shown to decrease symptoms in female patients with IBS. A
      related class of drugs, the 5-HT4 receptor agonists, is being developed for the
      treatment of constipation-predominant IBS. Further investigation into the role of
      spinal afferent neurons in visceral hypersensitivity is at the forefront of IBS
      research. Several experimental drug therapies for IBS are also discussed in this
      review including N-methyl-D-aspartate receptor antagonists, neurokinin-1 receptor
      antagonists, octreotide, clonidine and the selective M3 receptor antagonist,
      zamifenacin.

PMID- 11302288
TI  - Economics of lower urinary tract symptoms (LUTS) in older people.
AB  - Urinary incontinence is an area of clinical and social importance to older people
      and providers of care. This article provides an update on the 'symptom' of
      urinary incontinence and reviews the concept of lower urinary tract symptoms
      (LUTS). The challenges facing health services researchers working in this field
      are also discussed in terms of trying to quantify the size and extent of the
      underlying problem. Economic issues and work undertaken to evaluate the cost of
      LUTS are appraised and the common nonsurgical treatments for LUTS are described
      together with associated conditions and their cost implications. The cost to
      individuals and society of LUTS is generally underestimated and the importance of
      reducing its severity (if cure is not achievable) makes clinical and economic
      sense.

PMID- 11302289
TI  - Antihypertensive treatment in elderly patients aged 75 years or over: a 24-week
      study of the tolerability of candesartan cilexetil in relation to
      hydrochlorothiazide.
AB  - OBJECTIVE: To assess the safety and tolerability of the AT1-receptor blocker
      candesartan cilexetil in relation to the diuretic hydrochlorothiazide (HCTZ) in
      elderly patients. DESIGN AND SETTING: A multicentre, double-blind, randomised,
      parallel group study. 32 general practice centres and 3 hospital centres in
      Denmark and Finland participated in this study. PATIENTS: 185 patients aged > or
      =75 years with mean sitting diastolic blood pressure (DBP) of 95 to 114mm Hg.
      INTERVENTIONS: After a placebo run-in period of 4 to 8 weeks, patients were
      randomised to once daily treatment with candesartan cilexetil 8mg or HCTZ 12.5mg
      for 24 weeks. In both treatment groups the dosage could be doubled after > or =2
      weeks [according to blood pressure (BP) response] and, if necessary, subsequently
      decreased if the higher dosage was poorly tolerated. MAIN OUTCOME MEASURES:
      Proportion of patients with at least 1 adverse event; changes in laboratory
      values, electrocardiogram and BP during the double-blind treatment period.
      RESULTS: Once daily candesartan cilexetil 8 to 16mg was very well tolerated. The
      most common adverse events in both treatment groups were dizziness or vertigo and
      headache. Although the profile of adverse events was generally similar in the 2
      treatment groups, it was notable that hypokalaemia and hyperuricaemia were not
      found in patients treated with candesartan cilexetil but occurred in 8.1 and
      6.5%, respectively, of patients treated with HCTZ. At week 24, the adjusted mean
      changes in sitting DBP (24 hours postdose) from baseline were -12.0mm Hg [95%
      confidence interval (CI) -1 0.4 to -13.6] in patients treated with candesartan
      cilexetil and -11.4mm Hg (95% CI -9.3 to -13.6) in patients treated with HCTZ.
      The difference between treatments in favour of candesartan cilexetil was not
      statistically significant. CONCLUSIONS: This study shows that antihypertensive
      treatment with candesartan cilexetil in elderly patients (aged > or =75 years) is
      well tolerated with a good safety profile and avoids the metabolic adverse
      effects of diuretic therapy.

PMID- 11302290
TI  - Family decision-making to withdraw life-sustaining treatments from hospitalized
      patients.
AB  - BACKGROUND: With a national trend toward less aggressive treatment of
      hospitalized terminally ill patients, families increasingly participate in
      decisions to withdraw life-sustaining treatment. Although prior research
      indicates decision making is stressful for families, there have been no
      psychometric reports of actual stress levels and few discussions of the reasoning
      used by families compared to clinicians in reaching the decision. OBJECTIVES: The
      purpose of this study was to assess levels of family stress associated with
      decisions to withdraw life-sustaining treatments, to assess factors that affected
      stress, and to compare families and clinicians on their reasoning about the
      decision. METHODS: Data were collected from hospital decedent charts, family
      members of decedents, and clinicians who cared for decedents. Data from families
      were collected in individual interviews, shortly after decedent death and 6
      months later, using psychometric measures and semi-structured interview
      questions. Clinicians were interviewed once shortly following patient death.
      RESULTS: Family stress associated with the withdraw decision was high immediately
      following the death of the decedent and, while it decreased over time, remained
      high a half a year later. Several factors affected stress; most notably, stress
      was highest in the absence of patient advance directives. In reaching the
      decision, both families and clinicians prioritized what the patient would want,
      although families, more strongly than clinicians, endorsed doing everything
      medically possible to prolong the patient's life. CONCLUSIONS: Findings add
      compelling evidence for the power of advance directives, whether written or
      verbal, to reduce the stress associated with family decision-making.

PMID- 11302291
TI  - A model for predicting motor urge urinary incontinence.
AB  - BACKGROUND: While the historical interview has been shown to diagnose stress
      urinary incontinence (UI) with reasonable accuracy, it is less accurate in the
      diagnosis of urge or mixed UI. OBJECTIVES: To construct an optimal model for the
      diagnosis of motor urge UI, and to refine this model into a simplified instrument
      that can be used to diagnose motor urge UI during a routine incontinence
      evaluation. METHODS: A model was constructed to allow a more accurate diagnosis
      of motor urge UI using historical data. Initially, an optimal model was developed
      that used three key symptoms, age, gender, a history of neurologic disorder,
      obstruction diagnosed via voiding pressure study, and the urethral resistance
      algorithm to diagnose motor urge UI. A simplified model was then constructed
      using factors such as symptoms of motor urge UI, age, and gender that were
      readily accessible to the nurse when completing a routine UI evaluation. This
      simplified model was used to develop an instrument for the clinical diagnosis of
      motor urge UI. RESULTS: While the agreement between clinical and urodynamic
      diagnosis was relatively high among patients with genuine stress UI (93% accuracy
      rate), it was considerably less among patients with urge and mixed UI, yielding
      accuracy rates of 63% and 35%, respectively. An optimal model for diagnosing
      motor urge UI was constructed and provided an overall accuracy rate of 91%. A
      simplified model was then constructed and evaluated for performance by least
      squares fit test. It revealed an R2 of 0.85 and an adjusted R2 of 0.84.
      CONCLUSIONS: A combination of age, gender, and three key symptoms (diurnal
      frequency, nocturia, and symptom of urge incontinence) provide an accurate and
      clinically useful model for the diagnosis of motor urge UI. Additional research
      is recommended to test the validity and reliability of the instrument derived
      from this model.

PMID- 11302292
TI  - Attitudes toward physician-nurse collaboration: a cross-cultural study of male
      and female physicians and nurses in the United States and Mexico.
AB  - BACKGROUND: Inter-professional collaboration between physicians and nurses,
      within and between cultures, can help contain cost and insure better patient
      outcomes. Attitude toward such collaboration is a function of the roles
      prescribed in the culture that guide professional behavior. OBJECTIVES: The
      purpose of the study was to test three research hypotheses concerning attitudes
      toward physician-nurse collaboration across genders, disciplines, and cultures.
      METHOD: The Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration was
      administered to 639 physicians and nurses in the United States (n = 267) and
      Mexico (n = 372). Attitude scores were compared by gender (men, women),
      discipline (physicians, nurses), and culture (United States, Mexico) by using a
      three-way factorial analysis of variance design. RESULTS: Findings confirmed the
      first research hypothesis by demonstrating that both physicians and nurses in the
      United States would express more positive attitudes toward physician-nurse
      collaboration than their counterparts in Mexico. The second research hypothesis,
      positing that nurses as compared to physicians in both countries would express
      more positive attitudes toward physician-nurse collaboration, was also supported.
      The third research hypothesis that female physicians would express more positive
      attitudes toward physician-nurse collaboration than their male counterparts was
      not confirmed. CONCLUSIONS: Collaborative education for medical and nursing
      students, particularly in cultures with a hierarchical model of inter
      professional relationship, is needed to promote positive attitudes toward
      complementary roles of physicians and nurses. Faculty preparation for
      collaboration is necessary in such cultures before implementing collaborative
      education.

PMID- 11302293
TI  - The factorial survey: an experimental method to replicate real world problems.
AB  - BACKGROUND: Vignettes are used by nurse researchers use to determine how clinical
      judgments about patient care situations are made. However, when vignettes are
      designed there is often a restriction on the number of characteristics studied,
      which oversimplifies the richness and complexity of real world healthcare
      situations. OBJECTIVES: The purpose of this article is to describe a factorial
      survey. Its multilevel design of independent variables allows for real world
      complexity in a way not tested by a sample set of four to six identical
      vignettes. Nurses' judgments about patients' confusion and the application of
      restraints are used to illustrate the method. METHOD: The factorial survey is an
      experimental design that can be developed in three steps: (a) identifying and
      using the variables, (b) writing a coherent vignette, and (c) randomly generating
      the vignettes. RESULTS: The unit of analysis is the vignette and Ordinary Least
      Squares (OLS) regression is used for analyses. In the example provided on
      confusion recognition and restraint use, patient characteristics accounted for
      the majority of explained variance in confusion recognition of (40%, R2 = 0.40)
      and restraint intervention for (43%, R2 = 0.43). The results for both models were
      strikingly similar as the same patient characteristics all were significant
      predictors for confusion recognition and restraint use. CONCLUSIONS: The
      versatility of the factorial survey lies in the researcher's ability to use it to
      test judgments in a variety of complex clinical simulations, to aid in concept
      development, and to identify consensus and disagreement among nurses. The
      multilevel design of the independent variables allows for real world complexity
      in a way not tested by a sample set of four to six identical vignettes.

PMID- 11302294
TI  - Reading for writing.

PMID- 11302295
TI  - Psychosocial nursing therapy following sudden cardiac arrest: impact on two-year
      survival.
AB  - BACKGROUND: Although psychosocial therapy has been shown to reduce mortality
      after myocardial infarction, it is unknown whether the benefits of psychosocial
      therapy on mortality reduction extend to out-of-hospital sudden cardiac arrest, a
      main cause of cardiovascular mortality. OBJECTIVE: Describe efficacy of
      psychosocial therapy on two-year cardiovascular mortality in sudden cardiac
      arrest survivors. METHOD: Survivors of out-of-hospital ventricular fibrillation
      or asystole (N = 129), documented by electrocardiograms from registries of a
      citywide Medic One unit and two countywide emergency units, were randomized into
      a two group, experimental, longitudinal design. The intervention consisted of 11
      individual sessions, implementing three components: physiologic relaxation with
      biofeedback training focused on altering autonomic tone; cognitive behavioral
      therapy aimed at self-management and coping strategies for depression, anxiety,
      and anger; and cardiovascular health education. The primary outcome measure was
      cardiovascular mortality. RESULTS: Risk of cardiovascular death was significantly
      reduced 86% by psychosocial therapy, p = .03. Six of the seven cardiovascular
      deaths in the control group were caused by ventricular arrhythmias. The
      cardiovascular death in the therapy group was due to stroke. Controlling for
      depression, previous myocardial infarction, low ejection fraction, decreased
      heart rate variability, and ventricular ectopic beats had little impact on
      estimated treatment effect. The risk of all-cause mortality was reduced by 62% in
      the therapy group, p = .13. There were a total of three deaths in the therapy
      group and eight deaths in the control group. CONCLUSIONS: Psychosocial therapy
      significantly reduced the risk of cardiovascular death in sudden cardiac arrest
      survivors.

PMID- 11302296
TI  - Effects of entorhinal cortex lesions on sensory integration and spatial learning.
AB  - BACKGROUND: The entorhinal cortex provides sensory information to the hippocampus
      for memory and learning. Damage to the entorhinal cortex is common in patients
      who experience traumatic brain injury, stroke, and Alzheimer's disease.
      Entorhinal damage is assumed to interfere with sensory integration; however,
      substantive knowledge of behavioral patterns is lacking. OBJECTIVES: To describe
      specific behavioral deficits associated with entorhinal cortex injury related to
      special senses identification, sensory integration, and spatial learning. METHOD:
      Adult male rats received bilateral entorhinal cortex damage (n = 19) or sham
      surgery (n = 11) with a subset randomized to participate in special senses
      identification, exploration, and sensory integration testing. Spatial learning
      was examined using a water maze. RESULTS: Lesion and control animals were similar
      in special senses identification testing. Sensory integration was markedly
      impaired in lesion animals over 3 days for all integration tasks; however, travel
      deficit persisted for 4 days. By day 5 sensory integration ability was equal.
      Lesion animals were significantly impaired across all days of spatial learning
      for swim time (p = .0001) and directional heading error (p = .03). Control
      animals exposed to sensory testing demonstrated significantly more efficient
      learning (p = .005) on swim days 2 and 3 versus control animals not exposed to
      sensory testing. CONCLUSIONS: Early and prolonged behavioral changes are evident
      following entorhinal cortex damage including sensory integration deficits and
      persistent spatial learning impairment.

PMID- 11302297
TI  - Attention and symptom distress in women with and without breast cancer.
AB  - BACKGROUND: The cognitive capacity to direct attention (CDA) is essential for
      self-care and independent functioning. Older women may be more vulnerable to
      fatigue-related losses in CDA following surgery for breast cancer. Normal
      functional variations in CDA associated with aging might affect attentional
      responses in older women newly diagnosed with breast cancer, and factors such as
      extent of surgery or symptom distress might influence CDA over time. OBJECTIVES:
      To examine (a) differences in CDA and symptom distress in older women newly
      diagnosed with breast cancer as compared to a control group of older women
      without breast cancer; (b) the pattern of change in CDA and symptom distress from
      the pretreatment period to 3 months after surgery; and (c) to examine the
      relationship of CDA with symptom distress and extent of surgery over time.
      METHODS: Women, 55 to 79 years of age, newly diagnosed with breast cancer (N =
      47), were assessed with measures of CDA and symptom distress: (a) before surgery,
      (b) at 2 weeks postsurgery, and (c) 3 months postsurgery. To account for normal
      variations associated with aging, 48 women of similar age without breast cancer
      were assessed following a routine screening mammogram and 3 months later.
      RESULTS: Before treatment, the breast cancer group scored significantly lower
      than the control group (p < .05) on measures of CDA and higher on symptom
      distress. Repeated measures ANOVA showed significant main effects of group, but
      not time, for the measures of CDA and symptom distress with the breast cancer
      group having worse status than the control group. For CDA only, there was a
      significant group by time interaction effect (p = .005) so that the breast cancer
      group showed a gradual gain in CDA over time. CONCLUSIONS: Reduced performance in
      a cognitive function was observed before treatment and found to persist over an
      extended interval in older women newly diagnosed with breast cancer.

PMID- 11302298
TI  - Heart rate variability in adolescents and adults with type 1 diabetes.
AB  - BACKGROUND: Limited data are available regarding the onset or trajectory of
      cardiovascular autonomic deterioration in persons with type 1 diabetes.
      OBJECTIVE: To describe differences in heart rate variability among adolescents
      with type 1 diabetes, adults with type 1 diabetes who have coexisting renal
      failure, and adolescent and adult controls. RESEARCH DESIGN AND METHODS: A
      correlational design was used to compare the status of heart rate variability in
      adults with type 1 diabetes and renal failure (n = 62); healthy adult controls (n
      = 67); adolescents with type 1 diabetes (n = 55); and healthy adolescent controls
      (n = 28). Convenience samples of adult patients with diabetes awaiting kidney or
      pancreas and kidney transplantation, and adolescents with diabetes were recruited
      from local university-based clinics. Volunteers served as healthy controls. The
      short-term R-R variability measures included in this study were changes in heart
      rate with deep breathing and with the Valsalva maneuver. Twenty-four hour
      ambulatory heart rate monitoring with power spectral analysis was also obtained
      to assess longterm R-R variability. RESULTS: Adult patients with type 1 diabetes
      awaiting transplantation had significantly poorer heart rate variability measures
      than any of the other three populations studied (p < .0001). Adult control values
      also were significantly lower than either teenage controls or youths with
      diabetes (p < .05). Although most long-term R-R variability measures were lower
      in adolescents with diabetes versus controls, only one measure of parasympathetic
      modulation (i.e., pNN50) was significantly lower (p = .042). There were
      significant negative associations between HbA1c and sympathetic modulation (i.e.,
      low hertz) in both the adult group (r= -.406, p = .029) and the adolescent group
      (r= -.324, p = .025) with diabetes. CONCLUSIONS: Type 1 diabetes is associated
      with decreased heart rate variability, with the extent of the decrease related to
      the age of the individual and the severity of the disease.

PMID- 11302299
TI  - Iliacus hematoma and femoral nerve palsy after revision hip arthroplasty: a case
      report.
AB  - Femoral nerve palsy occurred in a 65-year-old man after he had undergone a
      revision total hip arthroplasty using cementless components. The magnetic
      resonance imaging scan showed a mass in the iliacus muscle. The mass showed
      increased signal intensity on T1-weighted and T2-weighted spin-echo images and
      contained linear septa and a nodule. The gadolinium-enhanced T1-weighted image
      showed a rim of significant enhancement in the nodule. The findings of magnetic
      resonance images were suggestive of iliacus hematoma and of liposarcoma. The
      patient underwent surgery, and the mass was identified as an iliacus hematoma.
      The femoral nerve was stretched by the hematoma. After removal of the hematoma,
      the nerve palsy was improved completely. Iliacus hematoma may occur after total
      hip arthroplasty, even without anticoagulant therapy. The hematoma might appear
      to be a liposarcoma on magnetic resonance imaging scans.

PMID- 11302300
TI  - Duration of symptoms and outcome of hemiresurfacing for hip osteonecrosis.
AB  - Thirty-seven hips with Ficat Stage II, III, or early IV osteonecrosis were
      treated with hemiresurfacing. The purpose of this study is to analyze
      specifically the clinical and radiographic results of patients who had
      hemiresurfacing to refine the indications for the procedure and identify factors
      substantially affecting clinical outcome and survivorship. At an average followup
      of 6.5 years, the average University of California Los Angeles hip scores for
      pain, walking, function, and activity improved significantly from 4.3, 6.0, 5.3,
      and 4.2 to 8.0, 8.8, 7.9, and 5.8. The overall survivorship was 79%, 59%, and 45%
      at 5, 10, and 15 years. Eleven hips have been converted: 10 hips for acetabular
      cartilage wear and one hip for femoral loosening. The average time to conversion
      was 7.5 years. A longer duration of symptoms before surgery (16.6 months versus
      12.1 months) was associated with a worse acetabular cartilage grading and
      suggested a relationship with a shorter time to conversion, although the
      difference was not statistically significant at the 5% level. Survivorship is
      better when preoperative symptoms are present for 1 year or less, possibly
      because the articular cartilage is healthier. When necessary, conversion to total
      hip replacement can be done without adverse results.

PMID- 11302301
TI  - Bone age delay in Perthes disease and transient synovitis of the hip.
AB  - Patients with transient synovitis of the hip were found to have a bone age delay
      similar to the one found in patients in the active stages of Perthes disease.
      This finding led to a study on the relationship between the bone and chronologic
      ages in patients affected by either disease, in activity, and in the residual
      stage through to the end of growth. Bone age of all patients was established by
      means of a radiograph of both wrists and hands and the quantified data were
      compared with the Greulich and Pyle Atlas. All the patients in the active stage
      of both diseases revealed a bone age delay with different values and different
      time evolution but with some degree of overlapping between the thirtieth and
      seventieth months of age. The bone age delay persisted after healing of the
      respective disease and tended to diminish with time in an erratic way until the
      age of puberty when the bone and chronologic ages assume similar values.
      Transient synovitis of the hip usually occurs in only one hip.

PMID- 11302302
TI  - Recurrent Legg-Calve-Perthes disease: case report and long-term followup.
AB  - This is the seventh reported case of recurrent Legg-Calve-Perthes disease. The
      report documents the initial onset in a boy 4 years of age with healing
      clinically and radiographically. The boy experienced recurrence of disease at 8
      years of age with last followup at 20 years of age. Tests related to blood
      hypercoagulability and hypofibrinolysis and certain genetic factors relevant to
      osteonecrosis of the bone are reported.

PMID- 11302303
TI  - How many members must an orthopaedic department have to teach effectively?
AB  - Although the subject matter contained in the curriculum of a medical school has
      expanded continuously, the time to present this material to the students has
      diminished. With the abandonment of most lectures in clinical subjects, students
      have been exposed to the surgical specialties by short required rotations through
      the services. Often these rotations are offered only as electives. However, the
      surgical specialties such as orthopaedic surgery have increased considerably in
      subject matter and scope. It no longer is possible to present the subject in a
      series of 10 or 12 lectures given by full-time or part-time faculty. Instead, to
      showcase the subject of orthopaedic surgery requires a clinical service that
      contains the full spectrum of the specialty from athletic injuries to scoliosis.
      Only in this way can the specialty attract the bright and capable students who
      will become the leaders of orthopaedics in the future. To field such a panoply of
      specialists requires a combined effort by the school, the hospital, and the
      private sector.

PMID- 11302304
TI  - Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis.
      ORTHOVISC Study Group.
AB  - A prospective, multicenter, randomized, double-blind, controlled trial was
      conducted in 226 patients with knee osteoarthritis to evaluate the safety and
      efficacy of intraarticular injections of sodium hyaluronate. Patients were
      randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic
      saline (control) and were observed for an additional 25 weeks. In comparison with
      the control group, among patients who completed at least 15 weeks of the study
      and whose Western Ontario and McMaster Universities Osteoarthritis Index pain
      score for the contralateral knee was less than 12 at baseline, sodium hyaluronate
      injection resulted in improvement in Western Ontario and McMaster Universities
      Osteoarthritis Index pain score, patient and investigator global assessments, and
      pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with
      sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score
      from Weeks 7 through 27, compared with 40% of control patients. In addition,
      nearly twice as many patients treated with sodium hyaluronate as with saline (30%
      versus 17%, respectively) achieved a net improvement of at least 7 units. In
      contrast to treatment with saline, Western Ontario and McMaster Universities
      Osteoarthritis Index pain score for the contralateral knee was inversely related
      to the magnitude of improvement after treatment with sodium hyaluronate. Few side
      effects were attributed to treatment, and no differences between treatment groups
      were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The
      incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline,
      1.5%). The results indicate that sodium hyaluronate treatment is well tolerated
      and produces statistically and clinically significant improvement of symptoms in
      patients with mild to moderate knee osteoarthritis in whom pain in the
      contralateral knee is relatively modest.

PMID- 11302305
TI  - Radiographic assessment in total knee arthroplasty.
AB  - Sixty-five total knee arthroplasties were evaluated by the Knee Society
      Radiological Evaluation System which was developed to encourage uniform reporting
      of the results of total knee arthroplasty. All patients were examined by three
      independent experienced radiologists 8.9 years after surgery (range, 3-16 years)
      to analyze the interobserver variability. For measurement of angles, high
      interobserver correlation was calculated for the prosthetic component angles and
      the femorotibial shaft angle. The comparison of the means indicated no
      significant differences except for the femorotibial shaft angle. For measurement
      of radiolucent lines, interobserver correlation was low for all components. The
      differences of the means were significantly different for all components. The
      results of interobserver variability of the patellar evaluation revealed high
      interobserver correlation for the patellar angle and for patellar subluxation and
      dislocation evaluation. For assessment of patellar mediolateral and
      superoinferior displacement, a low interobserver correlation was found. For
      radiographic assessment of total knee arthroplasty, the measurement of angles,
      including alpha, beta, femorotibial shaft angle, sagittal femoral and tibial
      component angle, patellar angle, and patellar subluxation and dislocation
      evaluation are recommended. The method of assessing radiolucent lines should be
      reconsidered.

PMID- 11302306
TI  - Intermetatarsophalangeal bursitis induced by a plantar epidermal cyst.
AB  - A 44-year-old woman was admitted to the authors' institution for evaluation of
      two masses in the right forefoot. Standard radiographs showed foci of
      calcification within the mass. Magnetic resonance imaging and macroscopic
      findings during surgery revealed the lesion was composed mainly of two different
      portions: dorsal cystic masses and a solid mass in the plantar side of the fifth
      metatarsal head. Histologic and immunohistochemical examinations showed that the
      former was an intermetatarsophalangeal bursitis induced by keratinous material,
      whereas the latter was a ruptured epidermal cyst. To the best of the authors'
      knowledge, the current case is the first report of intermetatarsophalangeal
      bursitis caused by an untreated epidermal cyst.

PMID- 11302308
TI  - Expanding the orthopaedist's role in the treatment of foot and ankle disorders.
AB  - Many opportunities exist and more will become available for expanding the role of
      orthopaedic surgeons in the treatment of patients with foot and ankle conditions
      in the United States. The current authors present the main areas of opportunity:
      giving comprehensive foot care to patients who already are treated by orthopaedic
      surgeons and the application of advanced scientific biotechnology that will
      improve outcomes for patients with foot and ankle conditions who currently do not
      have satisfactory treatment. Orthopaedic surgeons must maintain a high level of
      commitment in their education and professional availability to patients and
      primary care physicians to expand their participation in foot and ankle care.
      Networking with physician and nonphysician primary care providers and
      volunteering educational services for fellow professionals in the evaluation and
      treatment of the entire spectrum of foot and ankle conditions is necessary. The
      general orthopaedist and the orthopaedic foot and ankle specialist can share in
      the future of treatment of patients with foot and ankle conditions in the United
      States.

PMID- 11302307
TI  - Prediction of osteonecrosis by magnetic resonance imaging after femoral neck
      fractures.
AB  - Thirty-one patients undergoing internal fixation for femoral neck fractures who
      were examined by magnetic resonance imaging at 2, 6, and 12 months after surgery
      and who could be followed up more than 2 years were enrolled in the current
      study. The items investigated were timing of the appearance of the band image on
      T1 weighted images, magnetic resonance imaging classification, and plain
      radiographs. Band images were observed 2 months after surgery in eight patients
      and 6 months in 12 patients (39% of all patients). According to the location and
      extent of the band image on magnetic resonance imaging, one patient was
      classified in the B1 Group (lateral type), four patients in the B2 Group (surface
      type), three patients in the B3 Group (intermediate type), and four patients in
      the B4 Group (extended type). Band images appeared in all patients in the B4
      Group 6 months after surgery. Femoral heads of the patients in the B3 and B4
      Groups by magnetic resonance imaging classification all were collapsed. On plain
      radiographs, osteonecrosis of the femoral head could be diagnosed in eight
      patients between 11 and 24 months after injury. The interval giving the greatest
      sensitivity, specificity, and accuracy of the diagnosis of osteonecrosis of the
      femoral head by magnetic resonance imaging was 6 months after surgery.

PMID- 11302309
TI  - Intramedullary fibular graft for tibiotalocalcaneal arthrodesis.
AB  - The intramedullary fibular graft was used in four patients for tibiotalocalcaneal
      fusion. There were three men and one woman. The average age was 49.7 years
      (range, 35-73 years). The initial injuries were three pilon fractures and one
      ankle fracture. Tibiotalocalneal arthrodesis was performed as a salvage procedure
      for patients with significant posttraumatic arthritis of the ankle, concomitant
      subtalar arthritis, and severe osteopenia. The average followup was 28 months
      (range, 24-31 months). All the patients had successful arthrodesis and were
      satisfied with the outcome results. The average preoperative American Orthopaedic
      Foot And Ankle Society ankle-hindfoot score for the whole group was 49.5 (range,
      44-54) and improved postoperatively to 78.5 (range, 71-81). Three patients had a
      good score and one patient had a fair score. There was no postoperative infection
      or fracture of the graft.

PMID- 11302310
TI  - Reconstruction of the proximal humerus with the clavicle after tumor resection: a
      case report.
AB  - Reconstruction of the proximal humerus after resection for tumor and modification
      of the clavicular transposition procedure is described in which the blood supply
      of the clavicle is preserved and the clavicle is used to bridge the defect. An 11
      year-old boy presented with shoulder pain, and the diagnosis was osteosarcoma of
      the right proximal humerus. After resection of the sarcomatous proximal humerus,
      the clavicle was released with its periosteum remaining intact, and the clavicle
      was rotated downward around the acromioclavicular joint. A vascularized fibula
      supplemented the reconstruction in trying to gain length of the arm. The
      acromioclavicular joint and the vascular supply of the clavicle were preserved.
      Internal fixation from the clavicle and the fibula to the distal humerus was made
      with an AO plate and screws. Muscles around the proximal humerus were reattached
      to the clavicle. Range of motion of the shoulder was 80 degrees flexion, 85
      degrees abduction, 30 degrees external rotation, and 90 degrees internal
      rotation. Although the postoperative followup is relatively short, only 2 years,
      the functional advantages of this operation over other forms of reconstruction
      can be observed.

PMID- 11302311
TI  - The effect of adjuvant chemotherapy on osteoarticular allografts.
AB  - Two hundred lower extremity osteoarticular allografts (in 200 patients) performed
      for aggressive or malignant bone tumors between 1976 and 1997 included 124 grafts
      of the distal femur, 46 of the proximal tibia, and 30 of the proximal femur.
      Seventy-four patients did not receive chemotherapy, and 126 received either
      adjuvant or neoadjuvant therapy. The diagnoses, mean ages, and length of followup
      were different for the two groups because most of the patients in the
      chemotherapy group had osteosarcoma, whereas the largest number in the control
      group had chondrosarcoma or parosteal osteosarcoma. The extent of the surgery was
      essentially the same for both patient groups, as is reflected by a low recurrence
      rate (7% for the control and 6% for the chemotherapy group). A statistical
      comparison of the various parameters showed that the infection, fracture, and
      amputation rates were the same, but the nonunion rate was markedly increased in
      the patients who received chemotherapy (32% versus 12%). Cox regression and
      Kaplan-Meier studies showed that chemotherapy had a significant effect on
      outcome, with the success rates for the two groups being quite different (72%
      versus 56%). The results for the distal femur showed a greater effect than for
      either the proximal tibia or the proximal femur. Analysis of these data suggest
      the distal femur is perhaps the most prone to healing problems, possibly based in
      part on the extent of the surgery. A final study supports the concept that the
      results improved in later years, suggesting a modification or application of the
      drugs used, better selection of patients, and improvements in surgical technique.

PMID- 11302312
TI  - Free filet leg flap.
AB  - With extensive loss of local soft tissues after resection of a sarcoma, standard
      closure may not be possible. The large operative defect in this instance may
      necessitate a free tissue transfer. Use of a vascularized tissue transfer from
      the leg of the amputated extremity of a patient to close a hemipelvectomy defect
      is described.

PMID- 11302313
TI  - Soft tissue echinococcosis: a report of two cases and review of the literature.
AB  - Echinococcosis (hydatid cyst disease) is a zoonotic infection caused by the
      parasitic tapeworm Echinococcus. The larval stage of this parasite can implant in
      many organs of the body, most commonly the liver, and create internal budding
      cystic masses. Echinococcal cysts also can implant in soft tissues; however, a
      review of the literature revealed no published case with the patient initially
      presenting with a soft tissue mass. Two such cases are reported in the current
      study. Physicians who evaluate soft tissue masses, particularly in patients from
      Echinococcus-endemic areas, need to include echinococcosis in their differential
      diagnoses. The current treatment of choice for soft tissue echinococcosis is wide
      resection combined with perioperative medical therapy.

PMID- 11302314
TI  - Effects of high-frequency, low-magnitude mechanical stimulus on bone healing.
AB  - Recent studies have shown osteogenic effects of high-frequency mechanical
      stimuli. The purpose of this study was whether externally applied, high
      frequency, low-magnitude interfragmentary movements affect the process of bone
      healing. In 12 sheep, a transverse osteotomy with a 3 mm gap was created in the
      right metatarsus and externally stabilized by a rigid circular fixator. External
      stimulation was performed in six sheep with the use of ground-based vibration.
      The sheep were standing with their hind limbs on a platform that produced
      vertical movements resulting in interfragmentary movements of approximately 0.02
      mm magnitude at 20 Hz frequency. The other six sheep remained rigidly stabilized
      by external fixation during the 8-week study and served as a control group.
      Healing was assessed postmortem by densitometric and mechanical examinations. No
      significant differences were found between the two groups, although callus
      formation was slightly enhanced (11%) in the stimulated group compared with the
      control group. Mechanical stimuli attributable to weightbearing in the control
      group were sufficient enough to initiate callus formation even under rigid,
      external fixation. Thus, external mechanical stimulation with the stimulation
      design described in the current study might not be indicated for improvement of
      bone healing.

PMID- 11302315
TI  - Bending strength and holding power of tibial locking screws.
AB  - The bending strength and holding power of two types of specially designed tibial
      locking devices, a both-ends-threaded screw and an unthreaded bolt, were studied
      and compared with four types of commercially available tibial interlocking
      screws: Synthes, Howmedica, Richards, and Osteo AG. To test bending strength, the
      devices were inserted into a high molecular weight polyethylene tube and loaded
      at their midpoint by a materials testing machine to simulate a three point
      bending test. Single loading yielding strength and cyclic loading fatigue life
      were measured. To test holding power, the devices were inserted into tubes made
      of polyurethane foam, and their tips were loaded axially to measure pushout
      strength. The devices were tested with two different densities of foam materials
      and two different sizes of pilot holes. Insertion torque and stripping torque of
      the screws were measured first. Pushout tests were performed with each screw
      inserted with a tightness equal to 60% of its stripping torque. Test results
      showed that the yielding strength and the fatigue life were related closely to
      the inner diameter of the screws. The stripping torque predicted the pushout
      strength more reliably than did the insertion torque. All tested devices showed
      greater holding power in the foam with the higher density and with the smaller
      pilot holes. The both-ends-threaded screw had the highest pushout strength and a
      satisfactory fatigue strength. The unthreaded bolt had the highest fatigue
      strength but only fair holding power. Clinical studies of the use of these two
      types of locking devices are worthwhile.

PMID- 11302316
TI  - Changes in canine skeletal muscles during experimental tibial lengthening.
AB  - In 24 beagles, lengthening of the right tibia was performed by callus distraction
      after osteotomy and application of a ring fixator. Distraction was started at the
      fifth postoperative day, with a distraction rate of 0.5 mm twice per day, and
      ended after 25 days. A control group of six additional dogs underwent tibial
      osteotomy and external fixation without distraction. Twelve animals with and
      three animals without leg lengthening were euthanized immediately after the
      distraction period of 25 days (Group A); the remaining 15 dogs were euthanized
      after an additional consolidation phase of another 25 days (Group B). From the
      distracted right leg and from the left control leg the tibialis anterior muscle,
      extensor digitorum longus muscle, peroneus longus muscle, and gastrocnemius
      muscle were removed and studied by means of routine histologic, histochemical,
      and immunohistochemical analyses, and electron microscopic examination. The
      muscles of the control group showed no differences between the right and left
      sides. However, in the other 24 dogs of Groups A and B, the authors saw marked
      alterations affecting only the lengthened muscles but not the muscles of the
      control limbs. These changes were highly significant and included muscle fiber
      degeneration and regeneration, target fibers, central cores, minicores, marked
      endomysial and perimysial fibrosis, and atrophy of Type 1 and Type 2 fibers. In
      the consolidation period (Group B) fiber type grouping indicated that
      reinnervation had occurred. In addition, an increase in satellite cells and
      myoblasts and proliferation of nuclei were observed. The findings of the current
      study indicate that leg lengthening results not only in muscle fiber degeneration
      followed by regeneration and reinnervation but also in formation of new muscle
      tissue.

PMID- 11302317
TI  - Expression of basic fibroblast growth factor during distraction osteogenesis.
AB  - Distraction osteogenesis is a process of tissue regeneration under an external
      mechanical stimulation. In the study, the spatial and temporal expression
      patterns of basic fibroblast growth factor in the newly formed osseous tissue
      during distraction osteogenesis in goats were studied using immunohistochemistry.
      During the distraction period, the expression of basic fibroblast growth factor
      was observed in the osteoblasts on the newly formed trabecular bone and the bone
      formation front. The cells of osteoblastic lineage and the mesenchymal cells in
      the distraction callus also expressed basic fibroblast growth factor. The
      expression of basic fibroblast growth factor in the distraction period was
      stronger than that during the latency and consolidation periods. However, some
      osteoblasts still were expressing basic fibroblast growth factor in the
      consolidation periods. According to these results, basic fibroblast growth factor
      may have a local regulatory role during distraction osteogenesis. The tensile
      force may stimulate the expression of basic fibroblast growth factor in
      osteoblasts and other cell types.

PMID- 11302318
TI  - Occupational orthopaedics in this millennium.
AB  - Treatment of musculoskeletal pain in the workplace by early return to work and
      prevention is the future of occupational orthopaedics. Patients who receive
      workers' compensation comprise 20% of the general orthopaedist's practice, 65% of
      a hand surgeon's practice, and 90% of the independent medical examiner's
      practice. To improve the treatment outcomes for patients who receive workers'
      compensation, orthopaedists in this millennium will need knowledge about how
      individual and job risk factors can combine to result in musculoskeletal pain in
      the workplace. This knowledge will promote the safe return of their patients to
      the workplace after injury. With the prediction that more than 50% of the
      workforce in the United States will have experienced an occupational injury or
      illness, it is important for orthopaedists who are treating patients with work
      related injuries to understand how management of these workplace risk prevention
      programs will impact their patients and practice of orthopaedics. In this
      millennium, orthopaedists will need to know how to talk the language, interpret
      the information, and understand the benefits of early return to work and
      prevention of injuries in the workplace. The future will be about legislated
      prevention and healthcare in the workplace.

PMID- 11302319
TI  - Interstitial fluid pressure and blood flow in canine osteosarcoma and other
      tumors.
AB  - This study aims to characterize interstitial fluid pressure and blood flow in
      naturally occurring appendicular bone tumors in dogs because high pressure may
      influence the response of tumors to chemotherapy and radiation therapy. Eighteen
      client-owned dogs with naturally occurring appendicular bone tumors were included
      in this study. At the time of surgical biopsy, interstitial fluid pressure and
      blood flow were measured using wick-in-needle probes and laser Doppler flowmetry,
      respectively, within the soft tissue and bony components of the lesions and in
      normal muscle. Interstitial fluid pressure within the bony and soft tissue
      components of the tumors was significantly higher than interstitial fluid
      pressure in normal muscle. Blood flow in the bony component of the tumors was
      significantly lower than blood flow in normal muscle. There was no significant
      difference between blood flow in the soft tissue component of the tumors compared
      with that in normal muscle. Appendicular bone tumors in dogs have significantly
      higher interstitial fluid pressure and lower blood flow than do adjacent,
      unaffected soft tissues. The higher interstitial fluid pressure and lower blood
      flow may reduce tissue oxygenation and impede drug delivery. The effects of
      increased interstitial fluid pressure and decreased blood flow should be
      considered in the formulation of treatment strategies for the clinical management
      of appendicular bone tumors.

PMID- 11302320
TI  - Surgical technique for installing an eight-channel neuroprosthesis for standing.
AB  - A standardized surgical procedure to implant an eight-channel functional
      neuromuscular stimulation system in the lower extremities for standing, exercise,
      and transfers for individuals with spinal cord injury has been developed. The
      implanted components include: (1) one eight-channel receiver-stimulator, (2)
      epimysial electrodes, (3) intramuscular electrodes, and (4) inline connectors.
      The development process included identifying the target muscle set for electrode
      placement and the corresponding surgical approaches, determining the stages of
      the surgical procedure, and assessing the effectiveness and stability of the
      implanted neuroprosthesis. The bilateral muscle set consists of the vastus
      lateralis, the gluteus maximus, the semimembranosus, and the erector spinae.
      Surgical approaches to the nerve entry points were developed through a series of
      cadaveric studies and intraoperative tests. Electrode placement is related to
      bony landmarks and based on standard orthopaedic approaches. The components of
      the neuroprosthesis are installed in one surgical session, with three stages.
      This procedure has been applied successfully in seven individuals, resulting in
      strong, isolated stimulated contractions adequate to raise and lower the body,
      maintain standing with a walker, and perform pivot transfers. The standardized
      surgical procedure is repeatable and teachable and will be used in upcoming
      multicenter clinical trials of the implanted neuroprosthesis.

PMID- 11302321
TI  - Hereditary neuropathy with liability to pressure palsies: a case report.
AB  - Hereditary neuropathy with liability to pressure palsy is a rare autosomal
      dominant disorder characterized by multiple episodes of focal demyelinating
      neuropathies after minor trauma to peripheral nerves. It usually appears in early
      adulthood with recurrent attacks of pain, numbness, and muscular weakness along
      the distribution of the clinically affected nerve. Segmental demyelination and
      thickenings of the myelin sheath are the pathologic findings. Electrophysiologic
      studies show a nonuniform mild demyelinating neuropathy with prolonged distal
      latencies. Genetic tests are available to aid in diagnosis as molecular analysis
      has identified a deletion in the chromosome 17p11.2 in the majority of these
      patients. There is a paucity of information in the orthopaedic literature
      regarding hereditary neuropathy with liability to pressure palsy. A case report
      is presented of a patient with this disorder to promote awareness and recognition
      that this entity should be considered in patients with multiple nerve palsies.

PMID- 11302322
TI  - The evolution of medical technology: lessons from the Burgess Shale.
AB  - Many forthcoming medical advances-growth factors, tissue engineering, gene
      therapy, attachable prosthetic limbs, and implantable computers--are so new that
      as yet there is no clinical experience with them. Each therapeutic technique will
      evolve in an environment containing few guideposts to help judge its efficacy and
      safety. Recent developments in evolution theory (based on an analysis of Cambrian
      fossils in Canada's Burgess Shale quarry) suggest that evolution passes, at
      times, through innovative cycles of progress--when diversification of design
      leads to perfection of form--with the concomitant production of many unsuccessful
      models. The evolution of the total knee replacement is a perfect example of the
      process, because many of the early devices have proven to be dismal failures.
      However, modern knee replacements would not have been developed without them.
      Because the risk of unforeseen complications associated with new medical products
      cannot be discerned in advance, each patient-consumer should have the opportunity
      to intelligently weigh an innovative product's risk potential against its
      possible benefit. The proposal made here, for a temporary New Product status for
      new drugs and devices after a product is cleared by the Food and Drug
      Administration for general marketing, provides a mechanism for making such
      decisions.

PMID- 11302323
TI  - Orthopedic manpower.

PMID- 11302324
TI  - The increasing need for nonoperative treatment of patients with osteoarthritis.
AB  - Osteoarthritis affects more patients than almost any other musculoskeletal
      disorder. The number of patients suffering joint pain and stiffness as a result
      of this disease will increase rapidly in the next decade. Although operative
      treatments of patients with osteoarthritis will continue to improve and the
      number of operative procedures will increase slightly in the next decade, only a
      small fraction of the patients with osteoarthritis will require operative
      procedures. The most pressing healthcare need for the majority of patients with
      osteoarthritis is nonoperative care that helps relieve symptoms and improve
      function, and in some instances slows progression. In rare instances, the
      symptoms of osteoarthritis improve spontaneously, but most patients need
      nonoperative care for decades. Orthopaedists need to improve their ability to
      provide nonoperative care for patients with osteoarthritis. They should be
      skilled in the early diagnosis of osteoarthritis and in the use of current common
      nonoperative treatments including patient education, activity modification, shoe
      modifications, braces, oral analgesics, oral nonsteroidal antiinflammatory
      medications, oral dietary supplements, and intraarticular injections.
      Furthermore, orthopaedists should be prepared to incorporate new nonoperative
      treatments for patients with osteoarthritis into their practice.

PMID- 11302325
TI  - Expanding roles of the orthopaedic surgeon.
AB  - Many sources predict an oversupply of orthopaedic surgeons in the United States
      continuing into the next 30 years. The most attractive solution to this problem
      is to expand the scope of orthopaedic practice by regaining direct patient access
      to orthopaedic specialty care, by developing and bringing new technologies and
      treatments to the marketplace quickly, and by developing alternatives to the
      typical orthopaedic practice such as expanding nonoperative care, improving the
      quality of the office practice, and exploring volunteer opportunities.

PMID- 11302326
TI  - Musculoskeletal disease in the United States: who provides the care?
AB  - Musculoskeletal care is a big business in the United States. It is estimated that
      the cost of musculoskeletal care is in excess of $215 billion per year. Although
      orthopaedic surgeons are responsible for providing musculoskeletal care, a
      significant proportion of care is rendered by other healthcare providers
      including primary care physicians, neurosurgeons, physiatrists, podiatrists,
      physical therapists, and a cadre of alternative care providers including
      chiropractors, acupuncture specialists, and naturopaths. The purpose of the
      current study is to provide data regarding the provision of musculoskeletal care
      by those other than orthopaedic surgeons to determine what, if any, concerns
      exist among other providers regarding manpower issues, and to suggest
      alternatives for orthopaedic surgeons to maintain or perhaps increase their
      proportion of musculoskeletal care in the United States.

PMID- 11302327
TI  - Expanding the role of the orthopaedic surgeon in the treatment of osteoporosis.
AB  - Osteoporosis is an increasingly prevalent disease among the aging population, and
      osteoporotic features account for substantial morbidity, mortality, and
      healthcare costs associated with this disease. Because the disease is silent
      until a fracture occurs, the orthopaedic surgeon often may be the physician in
      the best position to establish the diagnosis and consider the initiation of
      appropriate treatment. Historically, osteoporosis has been underdiagnosed and
      treated, but new methods allow accurate diagnosis using bone densitometry, and a
      range of effective treatment options that can reduce fracture risk. Diagnosis and
      treatment of osteoporosis fits readily into an efficient algorithmic approach in
      the office practice of orthopaedics. Orthopaedic surgeons can play a major role
      in improving the treatment of osteoporosis and decreasing morbidity from this
      disease. In addition, this can augment the office practice of orthopaedics with a
      large yet relatively underserved patient population. Finally, densitometry
      services can provide modest supplemental revenue sources for an orthopaedic
      practice.

PMID- 11302328
TI  - Shared decision-making and the orthopaedic workforce.
AB  - Studies of physician workforce need a standard of an appropriately sized
      workforce to compare projections. Although many studies use average rates of
      healthcare use as a standard, regional benchmarks provide a pragmatic alternative
      approach to estimating a reasonably sized physician workforce and avoid many of
      the problems of needs- and demand-based planning. Wide geographic variations in
      the rates of many procedures, unexplained by differences in population
      characteristics, suggest that supply-induced demand or physician practice style
      or both may be the major determinates of the rates for these procedures. In the
      current study, the authors explore some of these differences in orthopaedic
      procedure rates and their implications for workforce planning. For example, the
      rates of hip fracture are fairly uniform across geographic regions, whereas the
      rates of spine surgery vary sixfold and the rates of spinal fusion vary 10-fold.
      Shared decision-making is the process of giving patients informed choices about
      their treatment options based on current best evidence. Careful studies of
      treatment effectiveness and shared decision-making hold the promise of allowing
      patients' preferences and values to determine the right rate of healthcare use.
      These rates could allow workforce projections to be compared with optimal
      benchmarks for future planning.

PMID- 11302329
TI  - Orthopaedic manpower: an overview.
AB  - What constitutes orthopaedic practice and how many orthopaedic surgeons are
      desirable for a given population has been discussed since the specialty was
      founded. The American Academy of Orthopaedic Surgeons began addressing this issue
      in January 1937. Extensive studies were done in the early 1970s with sponsorship
      from the American Academy of Orthopaedic Surgeons, the American College of
      Surgeons, the American Surgical Association, and the Division of Manpower
      Intelligence of the Department of Health Education and Welfare. These studies
      involved questionnaire surveys, Delphi panel modeling, and direct observation in
      a three-day time and motion study of a statistical sample of 150 practices. At
      the conclusion of these studies, it was observed that orthopaedics was largely a
      male specialty, practitioners preferred the surgical aspect of their practices to
      their office practices, that there was no type of practice that was more
      efficient than another, that the more orthopaedic surgeons there were in a
      population the more operative procedures were being done, and the character of
      the practice changes with the ratio of orthopaedist to population drops below 1
      to 15,000. After 30 years involvement in health manpower issues the author
      concludes that there is no substitute for developing a solid database and
      analyzing trends, that the predictions have been remarkably accurate and although
      honorable men and women may disagree on the interpretation of data, few will
      argue that there is a limit on the number of orthopaedic procedures that can be
      justified in the diagnosis and treatment of a population. The essence of
      professionalism is self regulation and doing first and foremost what is in the
      best interest of the patient and society whether there necessitates an increase
      or a decrease in the number of orthopaedic surgeons being trained or practicing
      in a given population.

PMID- 11302330
TI  - Orthopaedic workforce studies: 1980 to 1985.
AB  - A committee was appointed by the American Academy of Orthopaedic Surgeons in 1981
      to continue the orthopaedic workforce studies begun by D. Kay Clawson a decade
      earlier. The committee found that the rapid increase in orthopaedists graduating
      from residency programs between 1970 and 1982 had resulted in a workforce in
      which fully 1/2 of practicing orthopaedists certified by the American Board of
      Orthopaedic Surgery were younger than 45 years. At that time, orthopaedists
      graduated at the rate of 700 per year. If that rate continued and if nothing else
      changed, it was calculated that the number of practicing board-certified
      orthopaedists per 100,000 people in the United States would continue to increase
      for at least 20 more years. The effect of reducing resident output by 10%
      increments also was projected with the hope that this information might influence
      future planning. In fact, a 10% reduction in resident output was achieved and the
      current ratio of board-certified orthopaedists per 100,000 population is very
      close to that predicted. In addition, the 1981 orthopaedic workforce committee
      developed a map of the United States that showed the number of board-certified
      orthopaedists in each major zip code. This map was distributed to every
      allopathic residency program in the United States in the hope that displaying
      this map might encourage graduating residents to choose more underserved areas in
      which to begin their practices. Evidence obtained subsequently by interviewing
      candidates taking Part II of the American Board of Orthopaedic Surgery certifying
      examinations showed this map seemed to have had very little effect in correcting
      workforce maldistribution.

PMID- 11302331
TI  - Assessment of sexual activity in patients with back pain compared with patients
      with neck pain.
AB  - Recent research has shown significant adverse effects of chronic low back pain on
      sexual activity in 46% of patients. To establish whether and how chronic low back
      pain adversely affects sexual activity, a questionnaire-based study was conducted
      on a patient group (low back pain) and a comparison group (neck pain). Patients
      were administered a visual analog scale, a series of conventional questionnaires,
      and a specifically designed sexual activity questionnaire covering frequency of
      intercourse before and since onset of pain, discomfort during intercourse,
      satisfaction with sexual life, and comfortable and uncomfortable basic coital
      positions. Patients with low back pain reported more interference than did
      patients with neck pain, and women with low back pain were more affected than
      men. Compared with the other groups, women with low back pain had greater
      reduction in frequency of intercourse, more marked discomfort during intercourse,
      and more interference with their sexual lives. The most pain generating position
      was prone for both genders, and the most comfortable one was supine. Sexual
      impairment, more marked in women, seems to be related to the triggering of pain
      by intercourse and to psychologic factors.

PMID- 11302332
TI  - Orientation and osteoarthritis of the lumbar facet joint.
AB  - Several studies have shown an association between sagittal orientation of the
      facet joint and degenerative spondylolisthesis. There is currently no information
      available on the association between orientation of the facet joint and
      osteoarthritis. This study examined the association between orientation and
      osteoarthritis of the lumbar facet joints. One hundred eleven consecutive
      patients underwent plain radiography and magnetic resonance imaging. These
      patients were divided into two groups: No Degenerative Spondylolisthesis Group
      (98 patients) and Degenerative Spondylolisthesis Group (13 patients). In the No
      Degenerative Spondylolisthesis Group, segments with higher grades of
      osteoarthritis showed more sagittal orientation of the facetjoints at the L3-L4
      and L4-L5 levels. The facet joint was oriented significantly more sagittally in
      the Degenerative Spondylolisthesis Group than in the No Degenerative
      Spondylolisthesis Group at the L4-L5 and L5-S1 levels. The severity of facet
      joint osteoarthritis was significantly higher in the Degenerative
      Spondylolisthesis Group than in the No Degenerative Spondylolisthesis Group at
      the L3-L4, L4-L5, and L5-S1 levels. A significant association was found between
      sagittal orientation and osteoarthritis of the lumbar facet joints, even in
      patients without degenerative spondylolisthesis. Facet joint osteoarthritis,
      rather than spondylolisthesis, is the pathoanatomic feature that is associated
      with sagittal orientation of the facet joints in patients with degenerative
      spondylolisthesis.

PMID- 11302333
TI  - A clinical comparison of the anterolateral and posterolateral approaches to the
      hip.
AB  - Patients who had anterolateral and posterolateral approaches in total hip
      replacement surgery were compared clinically for limp, dislocation, hospital
      stay, and discharge disposition. The only statistical difference was that the
      posterior approach had a statistically higher dislocation rate. Although the
      number of patients with limp was higher in the anterolateral group, the
      difference was not statistically different.

PMID- 11302334
TI  - Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas.
AB  - Malignant gliomas maintain a poor prognosis and survival rate due to their marked
      local invasive growth and neovascularization. Matrix metalloproteinases (MMPs)
      have been implicated in glioma invasion and angiogenesis, but it is unknown
      whether they are produced by the tumor cells or surrounding stroma. Using in situ
      hybridization and immunohistochemistry, we found expression of mRNA for both
      gelatinase-A (MMP2) and gelatinase-B (MMP9) localized to tumor cells and vascular
      structures in glioma sections. Gelatinase-A protein expression was detected most
      prominently in tumor cells, with very little signal seen in vasculature.
      Gelatinase-B protein expression was prominent in vascular structures but was also
      expressed in tumor cells. Our data show that these proteases are produced by
      glioma cells and vascular structures and suggest that synthetic MMP inhibitors
      might be useful in this disease.

PMID- 11302335
TI  - Inhibition of cell growth in human glioblastoma cell lines by farnesyltransferase
      inhibitor SCH66336.
AB  - Ras activation occurs through stimulation of an upstream growth factor receptor
      such as epidermal growth factor receptor (EGFR). The ultimate effect of Ras is to
      induce nuclear transcription via a signaling pathway sequentially involving Raf,
      MAP kinase kinase (MEK), and mitogen-activated protein kinase (MAPK). To
      transform cells, Ras oncoproteins must be posttranslationally modified with a
      farnesyl group in a reaction catalyzed by farnesyl protein transferase.
      Farnesyltransferase inhibitors, therefore, have been proposed as potent
      anticancer agents. This study demonstrates the growth-inhibitory effects of
      farnesyltransferase inhibitor SCH66336 on human glioblastoma cell lines U-251 MG,
      U-251/E4 MG (a stably transfected cell line with elevated EGFR expression), and U
      87 MG. As determined by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl-2
      (4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) and viability assays, the
      concentration required to achieve 50% inhibition (IC50) ranged from 30 microM
      (single 24-h treatment) to 10 microM (5-day treatment). U-251/E4 MG with
      overexpression of EGFR were more sensitive than U-251 MG parental cells. These
      observations were also supported by soft agar analysis. Cells treated with
      SCH66336 underwent G2 arrest. Western blot analysis revealed a decrease in
      phospho-MAPK levels upon treatment with 10 microM SCH66336, whereas MAPK levels
      were unaffected by the drug. Interestingly, increased expression of EGFR was
      observed in U-251 MG and U-251/E4 MG but not in U-87 MG in the presence of the
      inhibitor. These results demonstrate that SCH66336 inhibits viability and
      anchorage-independent growth in a time- and dose-dependent manner in glioblastoma
      cell lines U-251 MG, U-251/E4 MG, and U-87 MG via a signal transduction pathway
      involving the down-regulation of phospho-MAPK. Overexpression of EGFR appears to
      alter cellular sensitivity to farnesyltransferase inhibitors. This may have a
      particularly important implication in glioblastoma, where over 50% of tumors have
      amplification and overexpression of EGFR.

PMID- 11302336
TI  - Analysis of genomic rearrangements associated with EGRFvIII expression suggests
      involvement of Alu repeat elements.
AB  - We have developed a polymerase chain reaction (PCR)-based strategy for the
      synthesis and analysis of rearranged epidermal growth factor receptor (EGFR)
      fragments associated with the vIII mutant receptor expressed in glioblastomas
      with EGFR amplification. The sequencing of aberrant tumor fragments showed that
      intragenic deletion rearrangements consistently involve an approximately 600-bp
      region in intron 7 of EGFR and several rearrangement sites interspersed
      throughout the large (>100 kb) first intron of this gene. Examination of the
      intron 7 breakpoint region revealed an Alu repeat element, and all intron 7
      rearrangement sites were located within or downstream of this repeat sequence.
      Analysis of intron 1 for similar sequences resulted in the identification of 11
      sites containing >80% homology with parts of the Alu element in intron 7. Reverse
      transcriptase-PCR and/or Western analysis of the tumors showed the presence of
      EGFRvIII cDNAs and/or proteins, respectively, in all cases for which a rearranged
      genomic fragment was generated by long-range PCR. Collectively, these data
      suggest that EGFR rearrangements, associated with the synthesis of the most
      common EGFR mutant, are mediated by a specific sequence element.

PMID- 11302337
TI  - Comparative genetic patterns of glioblastoma multiforme: potential diagnostic
      tool for tumor classification.
AB  - Cytogenetic and molecular genetic studies of glioblastoma multiforme (GBM) have
      shown that the most frequent alterations are gains of chromosome 7, losses of 9p
      loci and chromosome 10, and gene amplification, primarily of the epidermal growth
      factor receptor (EGFR) gene. Although this profile is potentially useful in
      distinguishing GBM from other tumor types, the techniques used tend to be labor
      intensive, and some can detect only gains or losses of genetic loci. Comparative
      genomic hybridization (CGH) is a powerful technique capable of identifying both
      gains and losses of DNA sequences. The present study compares the CGH evaluation
      of 22 GBM with classic cytogenetics, loss of heterozygosity by allelotyping, and
      gene amplification by Southern blot analysis to determine the reliability of CGH
      in the genetic characterization of GBM. The CGH and karyotypic data were
      consistent in showing gain of chromosome 7 accompanied by a loss of chromosome 10
      as the most frequent abnormality, followed by a loss of 9p in 17 of 22 GBM cases.
      Loss of heterozygosity of chromosomes 10 (19/22) and 9p (9/22) loci confirmed the
      underrepresentation by CGH. Genomic amplifications were observed by CGH in 5 of
      the 10 cases where gene amplification was detected by Southern blot analysis. The
      data show that CGH is equally reliable, compared with the more established
      genetic methods, for recognizing the prominent genetic alterations associated
      with GBM and support its use as a plausible adjunct to glioma classification.

PMID- 11302338
TI  - Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal
      human microglia, astrocytes, and glioma cells.
AB  - Apoptotic cells display signals that trigger phagocytic removal by macrophages or
      neighboring cells. To better understand the signals triggering phagocytosis of
      apoptotic glioma cells, and to identify the cells that might be involved in the
      phagocytic process, U-251 MG glioma cells were made apoptotic by etoposide (25
      microg/ml) treatment and were incubated with normal human astrocytes (NHA),
      glioma cells, or microglia. Extent of phagocytosis was assessed by an in vitro
      phagocytosis assay. After 3 h of incubation with apoptotic cells, phagocytes
      tested were washed to remove nonengulfed cells, then fixed, stained, and counted
      to determine phagocytosis index (PI). NHA, glioma cells, and microglia all
      phagocytosed apoptotic, but not nonapoptotic, glioma cells. Microglia, however,
      had a PI approximately 4-fold higher than did either NHA or glioma cells. Binding
      of phosphatidylserine (PS) on apoptotic glioma cell membranes by annexin-V
      inhibited phagocytosis by 90% in both microglia and NHA. The activity of an
      enzyme (scramblase) that moves PS from the inner cell membrane to the outer cell
      membrane was also increased in apoptotic glioma cells. These results suggest that
      a variety of cells present in and near gliomas in vivo can remove glioma cells in
      a PS-dependent scramblase-mediated fashion. Manipulation of scramblase and/or PS
      exposure in glioma cells may therefore be a means of triggering phagocytic
      removal of glioma cells.

PMID- 11302339
TI  - Recurrent astrocytoma in a child: a report of cytogenetics and TP53 gene mutation
      screening.
AB  - An 8-year-old girl presented with a cerebral tumor and 3 recurrences within 15
      months. The primary tumor was a low-grade astrocytoma, but the recurrences showed
      progressively malignant phenotypes with increasing mitotic activity and MIB-1
      labeling indices. Radiotherapy was given between the first and the second
      recurrences. Cytogenetic analysis of the first and the second recurrences showed
      abnormal karyotypes. There seemed to be 2 common breakpoints in these 2
      recurrences. TP53 gene mutation screening, using comprehensive denaturing
      gradient gel electrophoresis, revealed among others a possibly causative mutation
      of exon 5 in 3 of 4 tumor samples. The meaning of TP53 mutations in low-grade
      astrocytomas is still unclear, but the highly abnormal karyotypes, which are
      unusual in these tumors, probably provide genetic evidence for the unexpected
      aggressive behavior of the tumor in this patient.

PMID- 11302340
TI  - Treatment of progressive metastatic glomus jugulare tumor (paraganglioma) with
      gemcitabine.
AB  - Paragangliomas are rare tumors of the paraganglia composed of specialized neural
      crest cells arising in association with sympathetic ganglia. Here we report a
      case of progressive, metastatic paraganglioma (glomus jugulare tumor) responsive
      to single agent gemcitabine. In addition, a brief review of chemotherapy for
      paraganglioma follows the case presentation.

PMID- 11302341
TI  - Differentiation of radiographically indeterminate solitary pulmonary nodules
      with.
AB  - BACKGROUND: The purpose of this preliminary study was to evaluate the efficacy of
      positron emission tomography (PET) with [18F]fluoro-2-deoxyglucose (FDG) for
      differentiating benign from malignant solitary pulmonary nodules. METHODS: Twenty
      six patients (12 females, 14 males, age 27-79 years) with radiographically
      indeterminate solitary pulmonary nodules underwent FDG-PET and the findings were
      compared with the results of pathological examination of biopsy samples. FDG
      activity in the lesion was expressed as the ratio of lesion-to-background counts
      (L/B ratio) for semiquantitative analysis. RESULTS: The mean L/B ratio of
      malignant lesions (8.81+/-3.71, n = 20) was not significantly higher than that of
      benign lesions (4.71+/-3.00, n = 6) (p = 1.00). Using a cut-off L/B ratio of 5.0
      for malignancy, FDG-PET correctly detected 19 true positive and three true
      negative cases, but failed to detect three false positive (two abscesses and one
      cryptococcus) cases and one false negative (adenocarcinoma) case. The
      sensitivity, specificity, accuracy, positive predictive value and negative
      predictive value were 95, 50, 86, 75 and 85%, respectively. CONCLUSIONS: FDG-PET
      is a sensitive modality for detecting malignancy, but is not specific enough.
      Benign lung lesion with active inflammation could demonstrate high FDG uptake,
      making it difficult to differentiate from malignancy. In the future, we will
      increase the case numbers to evaluate further the utility of FDG-PET for
      differentiating radiographically indeterminate solitary pulmonary nodules.

PMID- 11302342
TI  - Intra-thoracic failure pattern and survival status following 3D conformal
      radiotherapy for non-small cell lung cancer: a preliminary report.
AB  - BACKGROUND: To study the intra-thoracic failure pattern, clinical target volume
      (CTV) and survival status following 3D conformal radiotherapy (3DCRT) boost for
      non-small cell lung cancer (NSCLC). METHODS: From May 1994 through June 1998, 33
      patients (26 male, seven female) with NSCLC were treated with a complete course
      of radiotherapy (RT) in our institute. Group A included 10 patients receiving
      radical operation and adjuvant postoperative RT. The other 23 patients (groups B
      and C) received definitive radiotherapy as local treatment. Among them there were
      seven cases as group B (stage I-II) and 16 cases as group C (stage III). Fifteen
      (15/33) patients received chemotherapy. The radiotherapy strategy constituted
      conventional AP/PA radiotherapy (RT) 19.8-45 Gy (median 39.6 Gy) plus 3DCRT boost
      6-34.2 Gy (median 20 Gy). The median total tumor dose was 59.6 Gy (ranging from
      39.8 to 64.8 Gy). Patients were followed up regularly (6/33) or until their death
      (27/33). Nineteen patients received follow-up chest computed tomography (CT). The
      relationship between intra-thoracic failure found by chest CT and the initial RT
      and boost RT fields was analyzed. Local failure was defined as one of the
      following: clinical disease progression, CXR progression or relapse noted by CT.
      The overall survival (OS) and local failure free survival (LFF) were obtained
      using the Kaplan-Meier method. RESULTS: Sixteen intra-thoracic failures were
      noted in 15 follow-up chest CT examinations, which included nine in-field
      relapses, three partial in-field relapses and four out-field relapses. The 2-year
      OS and LFF for groups A, B and C were 78.8/59.2, 14.2/16.7 and 6.2/7.1%
      respectively. RTOG grade III/IV complications included one pneumothorax (RTOG
      grade III). CONCLUSION: Our retrospective study showed that selective omission of
      contralateral mediastinal lymph node station irradiation may be appropriate in RT
      for NSCLC. Chest wall and pleural relapses may not be a negligible cause of intra
      thoracic failure after RT for NSCLC.

PMID- 11302343
TI  - Infrequent frameshift mutations in the simple repeat sequences of hMLH3 in
      hereditary nonpolyposis colorectal cancers.
AB  - BACKGROUND: A recently identified mismatch repair gene, hMLH3, contains two
      simple repeat sequence regions, (A)9 and (A)8, in its coding region. To clarify
      the role of hMLH3 in hereditary nonpolyposis colorectal cancer (HNPCC), we
      searched for hMLH3 somatic and germline mutations, particularly in the repeat
      regions, in 41 HNPCC patient cells. METHODS: We analyzed the hMLH3 (A)9 and (A)8
      repeats in 27 colorectal cancers with microsatellite instability (MSI) as well as
      in normal cells from 41 HNPCC patients by means of polymerase chain reaction
      single-strand conformation polymorphism. hMSH3 (A)8 and hMSH6 (C)8 repeats were
      also examined in these cancers. RESULTS: Frameshift mutations in the hMLH3 (A)9
      repeat were observed in 4/27 (14.8%) cancers with MSI, all of which showed the
      severe MSI phenotype. No mutations in the (A)8 repeat were found in any case. The
      mutation frequency of the hMLH3 (A)9 repeat was similar to that of the hMSH6 (C)8
      repeat (5/26, 19.2%), but was significantly lower than that of the hMSH3 (A)8
      repeat (16/27, 59.3%) (P < 0.001). All four cancers with hMLH3 mutations
      exhibited germline hMSH2 and/or somatic hMSH3 mutations. No germline mutation in
      the hMLH3 (A)9 or (A)8 repeat was detected in normal cells from the 41 HNPCC
      patients. CONCLUSION: hMLH3 mutations were infrequently observed in HNPCC cancers
      with MSI and they may be secondary to other mismatch repair gene mutations. Hence
      hMLH3 may only play a small role in HNPCC tumorigenesis.

PMID- 11302344
TI  - Clinical relevance of the concentrations of both pyrimidine nucleoside
      phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in colorectal
      cancer.
AB  - BACKGROUND: Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5
      fluorouridine (5'-DFUR) to 5'-fluorouracil (5-FU), which exerts an anti-cancer
      effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). We
      examined the possible correlation of the tissue concentrations of both PyNPase
      and DPD with the clinicopathological features of colorectal cancer. METHODS: In
      36 cases of colorectal cancer, the concentrations of both PyNPase and DPD in
      fresh-frozen samples from either tumor or normal tissue were quantified using
      ELISA. RESULTS: The concentration of PyNPase was found to be significantly higher
      in the tumor than in the normal tissue (p = 0.001), whereas DPD showed no
      difference. The tumor/normal tissue ratio of PyNPase was higher in advanced stage
      cases, and also in the presence of liver metastasis, lymph node metastasis and
      vessel invasion (each p < 0.05). On the other hand, the tumor/normal tissue ratio
      of DPD was also higher in advanced stage cases and also in the presence of vessel
      invasion (each p < 0.05), thus indicating a poor response to 5-FU. The
      PyNPase/DPD ratio, which is known to be correlated with the tissue concentration
      of 5'-DFUR, was higher in the tumor than in the normal tissue (p = 0.001).
      CONCLUSIONS: The tumor/normal tissue ratios of both PyNPase and DPD might be
      useful candidates for predicting the prognosis of colorectal cancer. The
      PyNPase/DPD ratio was higher in the tumor tissue than in the normal tissue;
      however, further investigations are needed to clarify the effectiveness of
      fluoropyrimidine therapy.

PMID- 11302345
TI  - Altretamine is an effective palliative therapy of patients with recurrent
      epithelial ovarian cancer.
AB  - BACKGROUND: Management of patients with recurrent epithelial ovarian cancer is
      difficult. Although several agents are active, responses are short-lived and
      observed in only a small number of patients. Side effects of these drugs are
      substantial. There is a need for more effective and less toxic therapies.
      Altretamine is a well tolerated oral agent with minimal toxicity. There are only
      a few trials evaluating its efficacy as a single agent in recurrent epithelial
      ovarian cancer. METHODS: We prospectively studied patients with recurrent
      epithelial ovarian cancer who were able to take oral medication and had adequate
      bone marrow, liver and renal functions. All had been previously treated with at
      least one platinum-based chemotherapy regimen and had either relapsed or failed
      to achieve an adequate response. RESULTS: Seventeen patients were studied. The
      commonest histological subtype was serous adenocarcinoma. Seven patients had
      platinum refractory disease. The mean duration of therapy was 6.1 months. Six
      patients (35%) achieved complete or partial remission, time to progression was
      6.0 months and mean overall survival was 15.1 months. Toxicity was primarily
      nausea, vomiting and asthenia and was easily manageable. CONCLUSION: Altretamine
      is an acceptable and apparently less toxic alternative to other cytotoxic drugs
      used for palliation of patients with recurrent epithelial ovarian cancer.

PMID- 11302346
TI  - A study of pretreatment nomograms to predict pathological stage and biochemical
      recurrence after radical prostatectomy for clinically resectable prostate cancer
      in Japanese men.
AB  - BACKGROUND: Accurate pretreatment identification of the risks that prostate
      cancer has extended beyond the gland and that it will recur would significantly
      influence practice patterns. Preoperative nomograms to predict such risks have
      not been developed for the oriental male population. METHODS: Construction of
      nomograms to predict preoperatively pathological outcome and early biochemical
      failure following radical prostatectomy in Japanese males was based on logistic
      regression analysis, with predicted probabilities and 95% confidence intervals
      for the final model being obtained by repeating the analysis on 1000 bootstrap
      samples from the original cohort. RESULTS: Prostate-specific antigen level,
      clinical stage and biopsy Gleason score contributed significantly to the
      prediction of pathological stage and of biochemical failure in the univariate
      analysis (p < 0.001). Combined use of these three variables predicted these
      treatment outcomes better than any single variable (p < 0.001). Nomograms
      combining these three variables to predict final pathological findings and early
      biochemical failure were then developed. The medians and 95% confidence intervals
      of the predicted probabilities are presented in the nomograms. CONCLUSIONS: This
      information enables clinicians to use their nomograms when counseling Japanese
      patients, leading to more informed treatment decisions and helping to identify
      those with a high risk of early biochemical failure. The nomograms may also be
      used to assure comparability of different treatment modalities in investigational
      trials.

PMID- 11302347
TI  - Nodular thickening of interlobar fissures: an early manifestation of malignant
      mesothelioma: a case report.
AB  - Two men with occupational exposure to asbestos were admitted to our hospital with
      minute pleural changes on their chest CT image. Conventional computed tomography
      (CT) scans of the chest showed slightly thickened interlobar fissures and a small
      amount of pleural effusion. In addition, high-resolution CT showed small nodular
      opacities on interlobar fissures. There were no intrapulmonary mass shadows,
      pleural plaques or other extrapulmonary mass shadows. These roentgenographical
      findings were very similar to each other. Hyarulonic acid values obtained from
      their pleural fluid were extremely high. Finally, we diagnosed them as having
      malignant mesothelioma using an immunocytochemical technique and
      electronmicroscopy. We conclude that HRCT is helpful in the diagnosis of
      malignant mesothelioma, particularly in its early manifestation such as nodular
      opacities of interlobar fissures.

PMID- 11302348
TI  - Facial nerve paralysis and paraplegia as presenting symptoms of acute myeloid
      leukemia.
AB  - Granulocytic sarcoma is an extramedullary tumor associated with acute or chronic
      leukemias or myeloproliferative disorders. Rarely, the tumor may be seen before
      the diagnosis of leukemia. Symptomatic facial nerve paralysis and spinal cord
      invasion by granulocytic sarcomas are also relatively uncommon. We present here a
      17-year-old-female patient who had facial nerve paralysis and paraplegia due to
      granulocytic sarcoma as the presenting symptoms of acute myeloid leukemia.

PMID- 11302349
TI  - Prostate cancer mortality rates by prefectures in Japan.

PMID- 11302350
TI  - Explaining adolescent exercise behavior change: a longitudinal application of the
      transtheoretical model.
AB  - The developmental decline and benefits of exercise are documented, however,
      relatively little is known about the mechanisms and motivations underlying
      adolescent exercise behavior This project investigates which variables drive
      exercise or are a consequence thereof, within the Transtheoretical Model (TTM).
      Baseline questionnaires (N = 819) were collected through 5 Canadian high schools.
      For this longitudinal investigation, all baseline participants were approached
      for a 3-year follow up. Follow-up questionnaire completers (n = 400: mean
      baseline age = 14.89, SD = 1.15, mean follow-up age = 17.62 years, SD = 1.18)
      were not different from noncompleters (n = 419) on all baseline variables, except
      for sex (54. 75% and 43. 68% females, respectively; p <. 003). Stages, processes,
      self-efficacy, pros and cons of exercise from the TTM, and self-reported exercise
      were assessed. Panel analyses revealed that although the directions of the
      relations were as hypothesized, the processes did not significantly lead to
      exercise or vice versa. As hypothesized, exercise leads to self-efficacy and pros
      and cons, showing that the TTM can serve as a framework to understand adolescent
      exercise behavior Future research needs to incorporate shorter assessment
      intervals and use larger samples to be able to look at adjacent stage
      transitions.

PMID- 11302351
TI  - Physician-based activity counseling: intervention effects on mediators of
      motivational readiness for physical activity.
AB  - In theory-based interventions for behavior change, there is a need to examine the
      effects of interventions on the underlying theoretical constructs and the
      mediating role of such constructs. These two questions are addressed in the
      Physically Active for Life study, a randomized trial of physician-based exercise
      counseling for older adults. Three hundred fifty-five patients participated
      (intervention n = 181, control n = 174; mean age = 65.6 years). The underlying
      theories used were the Transtheoretical Model, Social Cognitive Theory and the
      constructs of decisional balance (benefits and barriers), self-efficacy, and
      behavioral and cognitive processes of change. Motivational readiness for physical
      activity and related constructs were assessed at baseline, 6 weeks, and 8 months.
      Linear or logistic mixed effects models were used to examine intervention effects
      on the constructs, and logistic mixed effects models were used for mediator
      analyses. At 6 weeks, the intervention had significant effects on decisional
      balance, self-efficacy, and behavioral processes, but these effects were not
      maintained at 8 months. At 6 weeks, only decisional balance and behavioral
      processes were identified as mediators of motivational readiness outcomes.
      Results suggest that interventions of greater intensity and duration may be
      needed for sustained changes in mediators and motivational readiness for physical
      activity among older adults.

PMID- 11302352
TI  - Mood states and impedance cardiography-derived hemodynamics.
AB  - OBJECTIVE: This exploratory study investigated the relation between psychological
      mood states and hemodynamic variables obtained at rest. METHODS: We measured
      resting hemodynamic variables using impedance cardiography, blood pressure, heart
      rate, and the Profile of Mood States (POMS) in 71 participants. RESULTS: Mood
      states were not significantly associated with heart rate, systolic, diastolic, or
      mean arterial pressure. In comparison with these basic measures of physiology, a
      number of impedance derived measures of hemodynamics were associated with mood
      states. Log stroke volume was negatively correlated with POMS tension-anxiety (r
      = -.319, p = .009) and fatigue-inertia (r = -. 316, p = .009). Log cardiac output
      was negatively associated with fatigue-inertia (r = -.346, p < .01). Log total
      peripheral vascular resistance was positively correlated with POMS fatigue
      inertia (r = .276, p = .024). CONCLUSIONS: Our findings suggest that mood states
      are associated with hemodynamic variables underlying blood pressure.

PMID- 11302353
TI  - Effects of future writing and optimism on health behaviors in HIV-infected women.
AB  - Optimists (people who have positive expectations about the future) have been
      shown to perform more health-promoting behaviors than pessimists. This study
      attempts to alter individuals' levels of optimism, and thereby their health
      behaviors, by having them write about a positive future. HIV-infected women (N =
      40) on combination therapies were randomly assigned to write about a positive
      future or assigned to a no-writing control group. Among participants who were low
      in optimism, the writing intervention led to increased optimism, a trend toward
      increased self-reported adherence to medications, and decreased distress from
      medication side effects, compared to controls who did not write. Participants who
      were high in optimism showed the opposite effects after writing about the future.
      Results suggest that a future-oriented writing intervention may be apromising
      technique to increase medication adherence and decrease symptom distress in
      pessimistic individuals.

PMID- 11302354
TI  - History of affective disorder and the temporal trajectory of fatigue in
      rheumatoid arthritis.
AB  - This study examines whether the general level and rate of change of fatigue over
      time is different for those rheumatoid arthritis (RA) patients with and those
      without a history of affective disorder (AD). Four hundred fifteen RA patients
      from a national panel had yearly telephone interviews to obtain fatigue and
      distress reports, and a one-time semistructured assessment of the history of
      depression and generalized anxiety disorder Growth-curve analysis was used to
      capture variations in initial fatigue levels and changes in fatigue over 7 years
      for those with and without a history. RA patients with a history of major AD
      reported levels of fatigue that were 10% higher than those without a history in
      the 1st year of the study. Their fatigue reports remained elevated over 7 years.
      Further analysis showed that the effects of a history of AD on fatigue are fully
      mediated through current distress, although those with a history had a
      significantly smaller distress-fatigue slope. Thus, a history of AD leaves RA
      patients at risk for a 7-year trajectory of fatigue that is consistently higher
      than that of patients without a history. The elevation in fatigue reports is, at
      least in part, a function of enduring levels of distress.

PMID- 11302355
TI  - Brief cognitive interventions for burn pain.
AB  - This study tested the efficacy of 2 brief cognitive interventions in
      supplementing regular medical treatment for pain during burn dressing change.
      Forty-two burn inpatients were randomly assigned to 3 groups: sensory focusing,
      music distraction, and usual care. Patients reported pain, pain relief
      satisfaction with pain control, and pain coping strategies. The sensory focusing
      group reported greater pain relief compared to the music distraction group and a
      reduction in remembered pain compared to the usual care group, although group
      differences were not observed on serial pain ratings. In addition, after
      controlling for burn size and relevant covariates, regression analyses indicated
      that catastrophizing predicted pain, memory for pain, and satisfaction with pain
      control. Refinement of the sensory focusing intervention is warranted to reduce
      catastrophic thinking and improve pain relief

PMID- 11302356
TI  - Evaluation of psychosocial measures for understanding weight-related behaviors in
      pregnant women.
AB  - The greatest weight gain for US. women occurs during the childbearing years of 25
      to 34, and many obese women attribute their adult weight gain to childbearing.
      Few studies have examined psychosocial influences on women's behaviors during
      pregnancy, in part because of the lack of valid and reliable measures of
      psychosocial constructs relevant to pregnant women. Based on existing theory and
      an in-depth interview study, the psychosocial constructs of locus of control,
      self-efficacy, body image, feelings about motherhood, and career orientation were
      identified. Scales for each construct were constructed by drawing items from
      existing validated scales and writing items based on the in-depth interviews;
      their content validity assessed using factor analysis with oblique rotation and
      their reliability using Cronbach's alpha. Construct validity was assessed by
      examining the associations between scale scores and preexisting conditions of
      participants. Data for evaluating the scales came from a study of 622 pregnant
      women in a rural health care system who completed questionnaires and whose
      medical records were audited. Cronbach's alpha of the scales ranged from 0.73 to
      0.89. Scale scores were strongly associated with lifestyle behaviors, body
      weight, and demographic characteristics of the participants. The analysis
      provides evidence of the validity of measures of psychosocial factors related to
      health behaviors of pregnant women. These measures should be useful in studying
      weight-related behaviors in pregnant women.

PMID- 11302357
TI  - The role of gender and family support on dietary compliance in an African
      American adolescent hypertension prevention study.
AB  - Social support experiences vary markedly across gender groups, and little is
      known about the role of social support in promoting healthy dietary compliance in
      African American adolescents who are at increased risk for developing
      hypertension. This study examined the relation between gender, dietary social
      support, and compliance to a low sodium diet. Casual blood pressures were also
      examined in relation to dietary compliance and gender One hundred eighty-four
      healthy African American adolescents (83 boys, 101 girls) participated in an
      intensive 5-day low sodium diet (50 mEq/24 hr) as part of a hypertension
      prevention program. Emotional dietary social support from family members and
      friends was measured at baseline. Compliance was defined as urinary sodium
      excretion of < or = 50 mEq/24 hr at postsodium restriction. The results indicated
      a significant Gender x Compliance effect for positive family support (p < .05).
      Girls who were compliant reported higher levels of dietary support from family
      members (19.2 +/- 7.8) than boys who were compliant (16.9 +/- 7.0). In contrast,
      boys who were compliant reported lower levels of dietary support from family
      members (16.9 +/- 7.0) than boys who were not compliant (20.2 +/- 7.5). Systolic
      blood pressure showed a trend toward decreasing in compliant participants (104.4
      +/- 8.4 vs. 101.7 +/- 8.0, mm Hg, p < .06), but the effect diminished when
      Quetelet Index (kg/m2) was controlled for in the analyses (p < .12). These
      results suggest that higher levels of emotional dietary support from family
      members are associated with better adherence to short-term sodium restriction for
      African American girls as compared to boys. Further research is needed to
      determine the long-term impact of social support on sodium restriction in
      adolescent populations.

PMID- 11302358
TI  - Religious attendance increases survival by improving and maintaining good health
      behaviors, mental health, and social relationships.
AB  - Several recent prospective analyses involving community-based populations have
      demonstrated a protective effect on survival for frequent attendance at religious
      services. How such involvement increases survival are unclear. To test the
      hypothesis that religious attendance might serve to improve and maintain good
      health behaviors, mental health, and social relationships, changes and
      consistencies in these variables were studied between 1965 and 1994 for 2,676
      Alameda County Study participants, from 17 to 65 years of age in 1965, who
      survived to 1994. Measures included smoking, physical activity, alcohol
      consumption, medical checkups, depression, social interactions, and marital
      status. Those reporting weekly religious attendance in 1965 were more likely to
      both improve poor health behaviors and maintain good ones by 1994 than were those
      whose attendance was less or none. Weekly attendance was also associated with
      improving and maintaining good mental health, increased social relationships, and
      marital stability. Results were stronger for women in improving poor health
      behaviors and mental health, consistent with known gender differences in
      associations between religious attendance and survival. Further understanding the
      mechanisms involved could aid health promotion and intervention efforts.

PMID- 11302359
TI  - The Nacirema revisited.

PMID- 11302360
TI  - Word-processing training and retraining: effects of adult age, experience, and
      interface.
AB  - Novice (Experiment 1) and experienced (Experiment 2) young, middle-aged, and
      older adults learned a new word-processing application in keystrokes, menus, or
      menus-plus-icons interface conditions. Novices showed strong age differences in
      the time to complete the 3-day tutorial and in declarative and procedural tests
      of word-processing knowledge. Menus and menus-plus-icons were superior to
      keystrokes condition. though interface did not interact with age. Experienced
      users showed age-related slowing in learning rate but minimal age differences in
      test performance when retrained on a new word-processing program. Age and
      computer experience accounted for much of the variance in both learning time and
      word-processing performance; interface type, speed of processing, and spatial
      generation ability made additional contributions. Experience interacted with age
      to predict performance. Implications for training and retraining older workers
      are discussed.

PMID- 11302361
TI  - Age-specific problems in rhythmic timing.
AB  - The authors investigated performance in 2 rhythm tasks in young (M = 23.8 years)
      and older (M = 71.4 years) amateur pianists to test whether slowing of a central
      clock can explain age-related changes in timing variability. Successive
      keystrokes in the rhythm tasks were separated by either identical (isochronous)
      time intervals or varying (anisochronous) intervals. Variability was comparable
      for young and older adults in the isochronous task; pronounced age effects were
      found for the anisochronous rhythm. Analyses of covariances between intervals
      rule out slowing of a central clock as an explanation of the findings, which
      instead support the distinction between target specification, timekeeper
      execution, and motor implementation proposed by the rhythm program hypothesis (D.
      Vorberg & A. M. Wing, 1996). Age stability was found at the level of motor
      implementation, but there were age-related deficits for processes related to
      target-duration specification.

PMID- 11302362
TI  - Age, working memory, and on-line syntactic processing in sentence comprehension.
AB  - One hundred twenty-seven individuals who ranged in age from 18 to 90 years were
      tested on a reading span test and on measures of on-line and off-line sentence
      processing efficiency. Older participants had reduced working-memory spans
      compared with younger participants. The on-line measures were sensitive to local
      increases in processing load, and the off-line measures were sensitive to the
      syntactic complexity of the sentences. Older and younger participants showed
      similar effects of syntactic complexity on the on-line measures. There was some
      evidence that older participants were more affected than younger participants by
      syntactic complexity on the off-line measures. The results support the hypothesis
      that on-line processes involved in recognizing linguistic forms and determining
      the literal, preferred, discourse-coherent meaning of sentences constitute a
      domain of language processing that relies on its own processing resource or
      working-memory system.

PMID- 11302363
TI  - Situation models and aging.
AB  - Younger and older adults were tested for their ability to process and retrieve
      information from texts. The authors focused on the construction and retrieval of
      situation models relative to other types of text representations. The results
      showed that during memory retrieval, younger adults showed superior memory for
      surface form and textbase knowledge (what the text was), whereas older adults had
      equivalent or superior memory for situation model information (what the text was
      about). The results also showed that during reading, older and younger adults
      were similar in their sensitivity to various aspects of the texts. Overall, these
      findings suggest that although there are age-related declines in the processing
      and memory for text-based information, for higher level representations, these
      abilities appear to be preserved. Several possibilities for why this is the case
      are discussed, including an in-depth consideration of one possibility that
      involves W. Kintsch's (1988) construction-integration model.

PMID- 11302364
TI  - Event-related brain potential evidence of spared knowledge in Alzheimer's
      disease.
AB  - The authors recorded event-related brain potentials (ERPs) to picture primes and
      word targets (picture-name verification task) in patients with Alzheimer's
      disease (AD) and in elderly and young participants. N400 was more negative to
      words that did not match pictures than to words that did match pictures in all
      groups: In the young, this effect was significant at all scalp sites; in the
      elderly, it was only at central-parietal sites; and in AD patients, it was
      limited to right central-parietal sites. Among AD patients pretested with a
      confrontation-naming task to identify pictures they could not name, neither the
      N400 priming effect nor its scalp distribution was affected by ability to name
      pictures correctly. This ERP evidence of spared knowledge of these items was
      complemented by 80% performance accuracy. Thus, although the name of an item may
      be inaccessible in confrontation naming, N400 shows that knowledge is intact
      enough to prime cortical responses.

PMID- 11302365
TI  - Demographic, health, cognitive, and sensory variables as predictors of mortality
      in very old adults.
AB  - Cognitive and sensorimotor predictors of mortality were examined in the
      Australian Longitudinal Study of Ageing, controlling for demographic and health
      variables. A stratified random sample of 1,947 males and females aged 70 and
      older were interviewed, and 1,500 were assessed on measures of health, memory.
      verbal ability, processing speed, vision, hearing, and grip strength in 1992 and
      1994. Analyses of incident rate ratios for mortality over 4- and 6-year periods
      were conducted using Cox hierarchical regression analyses. Results showed that
      poor performance on nearly all cognitive variables was associated with mortality,
      but many of these effects were explained by measures of self-rated health and
      disease. Significant decline in hearing and cognitive performance also predicted
      mortality as did incomplete data at Wave 1. Results suggest that poor cognitive
      performance and cognitive decline in very old adults reflect both biological
      aging and disease processes.

PMID- 11302366
TI  - The influence of expertise and task factors on age differences in pilot
      communication.
AB  - The influence of expertise and task factors on age differences in a simulated
      pilot-Air Traffic Control (ATC) communication task was examined. Young, middle
      aged, and older pilots and nonpilots listened to ATC messages that described a
      route through an airspace, during which they referred to a chart of this
      airspace. Participants read back each message and then answered a probe question
      about the route. It was found that pilots read back messages more accurately than
      nonpilots, and younger participants were more accurate than older participants.
      Age differences were not reduced for pilots. Pilots and younger participants also
      answered probes more accurately, suggesting that they were better able to
      interpret the ATC messages in terms of the chart in order to create a situation
      model of the flight. The findings suggest that expertise benefits occur for
      adults of all ages. High levels of flying experience among older pilots (as
      compared with younger pilots) helped to buffer age-related declines in cognitive
      resources, thus providing evidence for the mediating effects of experience on age
      differences.

PMID- 11302367
TI  - Age differences in dual-task interference are localized to response-generation
      processes.
AB  - Dual-task differences in younger and older adults were explored by presenting 2
      simple tasks, with the onset of the 2nd task relative to the 1st task carefully
      controlled. The possibility of an age-related reduction in the ability to
      generate and execute 2 similar motor programs was explored by requiring either a
      manual response to both tasks or a manual response to the 1st and an oral
      response to the 2nd and was confirmed by the evidence. The age-related
      interference was greater than would be expected from a general slowing of
      processing in older adults. The possibility of an age-related reduction in the
      capacity to process 2 tasks in the same perceptual input modality was explored by
      presenting both tasks in the visual modality or the 1st task in the auditory
      modality and the 2nd task in the visual modality and was not supported by the
      evidence. There was greater interference when both tasks were in the same
      modality, but it was equivalent for older and younger adults. Age differences in
      dual-task interference appear quite localized to response-generation processes.

PMID- 11302368
TI  - An event-related potential evaluation of involuntary attentional shifts in young
      and older adults.
AB  - Involuntary shifts in attention to irrelevant stimuli were studied in elderly and
      young volunteers during a dichotic-listening task. Event-related potentials and
      behavioral measures were recorded. Volunteers heard pairs of tones presented with
      2 different stimulus onset asynchronies (SOAs). To-be-ignored tones were
      presented to the left ear, followed by to-be-attended tones to the right ear.
      Left-ear tones were a frequent standard (700 Hz) and an infrequent small (650 Hz)
      and large (500 Hz) deviant. Right-ear tones (1500 Hz) were presented with 2
      equiprobable intensities. Volunteers responded to the lower intensity stimulus.
      Behavioral performance was impaired at the short SOA when to-be-ignored large
      deviants preceded to-be-attended targets, but more so for the elderly volunteers.
      Large deviants also elicited the mismatch negativity (MMN) and P3a for both age
      groups. It was concluded that the more impaired behavioral performance observed
      for the elderly was due to greater sensitivity to output from the MMN system by a
      frontal lobe system responsible for the maintenance of attentional focus.

PMID- 11302369
TI  - Patterns of resource allocation are reliable among younger and older readers.
AB  - Younger and older adults read short expository passages across 2 times of
      measurement for subsequent comprehension or recall. Regression analysis was used
      to decompose word-by-word reading times into resources allocated to word- and
      textbase-level processes. Readers were more sensitive to these demands when
      reading for recall than when reading for comprehension. Patterns of resource
      allocation showed good test-retest reliabilities and were predictive of memory
      performance. Within age group, resource allocation parameters were not
      systematically correlated with other individual-difference measures, suggesting
      that strategies of on-line resource allocation may be a unique source of
      individual differences in determining comprehension of and memory for text. Age
      differences in allocation patterns appeared to reflect general slowing among the
      older adults. Because older adults showed equivalent memory performance to that
      of younger readers, the reading time data may represent the on-line resource
      allocation needed for comparable outcomes among older and younger readers.

PMID- 11302370
TI  - Ain't misbehavin': the effects of age and intentionality on judgments about
      misconduct.
AB  - In 2 person perception experiments, young and older perceivers read a scenario
      about a young or old female target who leaves a store without paying for a hat.
      In Experiment 1, the target claims she forgot she was wearing the hat when
      questioned by the manager. Perceivers thought the manager would have greater
      sympathy, less anger, and would recommend less punishment when the target was
      old. In Experiment 2, the target clearly forgot to pay for the hat, clearly stole
      it, or had ambiguous intentions. In the ambiguous condition, perceivers
      attributed the young target's behavior more to stealing and the old target's
      behavior more to forgetting. In the forget condition, young perceivers had equal
      sympathy for the young and old targets and held them similarly responsible, but
      older perceivers had greater sympathy for the forgetful old target and held her
      less responsible than they did the forgetful young target.

PMID- 11302371
TI  - Age differences in the selection of mental sets: the role of inhibition, stimulus
      ambiguity, and response-set overlap.
AB  - Switching between tasks leads to response-time (RT) costs at switch points (local
      switch costs) and often to RT costs at no-switch transitions that occur in the
      context of a task-switching block (global set-selection costs). With trial-to
      trial cuing of tasks, moderate age effects were obtained for local switch costs,
      but large age effects were obtained for global selection costs. In Experiment 1,
      set-specific inhibition was found to be at least as large in old as in young
      adults, thus ruling out an inhibition deficit as a reason for age differences in
      global costs. In Experiment 2, large age differences in global costs were limited
      to conditions of ambiguous stimuli and full response-set overlap. This pattern of
      results suggests a greater reliance on set-updating processes in old than in
      young adults. The role of these processes is to ensure unambiguos internal
      control settings when ambiguity arises from stimuli and response specifications.

PMID- 11302372
TI  - Sarco(endo)plasmic reticulum calcium pumps: recent advances in our understanding
      of structure/function and biology (review).
AB  - This review examines the structure and function of the sarco(endo)plasmic
      reticulum calcium pump (SERCA1a) in the light of the recent publication of the
      2.6 A resolution structure of this protein, and looks at the increasing awareness
      of the key role played by SERCAs in calcium signalling. The roles played by the
      calcium pump isoforms, SERCA1a/b, SERCA2a/b and SERCA3a/b/c in cellular function
      are discussed, and the modulation of SERCA activity by phospholamban, sarcolipin
      and other modulatory influences is examined. The recent discoveries of human
      SERCA mutations leading to disease states is reviewed, and the insights into
      SERCA function using transgenic approaches are outlined.

PMID- 11302373
TI  - Use of hydrophobic moment plot methodology to aid the identification of oblique
      orientated alpha-helices.
AB  - A number of alpha-helix forming peptides have been reported which appear to
      promote membrane fusion and other biological events related to the disruption of
      a hydrophobic/hydrophilic interface, due to the presence of a hydrophobicity
      gradient along the helical long axis. When alpha-helices from this class were
      analysed according to hydrophobic moment plot methodology a linear association
      was found to exist between the mean hydrophobic moment, <microH>, and the
      corresponding mean hydrophobicity, <H0>. This association was described by the
      least squares regression line: <microH>=0.508-0.422<H0> and, here, a methodology
      to aid the prediction of oblique orientated alpha-helices is presented, based on
      a 99% prediction band around this regression line. This methodology is intended
      to provide an initial identification of candidates for further investigation by
      other techniques such as the molecular hydrophobic potential and laboratory based
      experimentation, not to assign function.

PMID- 11302374
TI  - Lipid phase separation correlates with activation in platelets during chilling.
AB  - When human platelets are chilled below 22 degrees C, they spontaneously activate,
      a phenomenon that severely limits their storage life. It has previously been
      proposed that there is a correlation between cold-induced platelet activation and
      passage of the membranes through a liquid-crystalline to gel phase transition.
      Because animal models are essential for developing methods for cold storage of
      platelets, it is necessary to investigate such a correlation in animal platelets.
      In this work, horse platelets were used as a model, and it was found that cold
      induced morphological activation is related to the lipid phase transition. Using
      fluorescence microscopy with the lipophilic fluorescent dye 1,1'-dioctadecyl
      3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (Dil-C18), and Fourier
      transform infrared spectroscopy (FTIR), it was found that lipid phase separation
      occurs during cooling and low temperature storage. Furthermore, removal of
      cholesterol from the plasma membrane also induced a phase separation, possibly
      between specific phospholipid classes. Steady-state fluorescence anisotropy of
      1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium-DPH (TMA-DPH) were
      compared in cells and multilamellar vesicles (MLV) composed of platelet lipids.
      Cholesterol depletion led to a decrease in the fluorescence anisotropy of the two
      probes, which can be explained by changes in the order of the phospholipid
      molecules. In addition, the lipid composition and fatty acid profile of the
      cellular phospholipids were determined. Based of the similarities between horse
      and human platelets, it is suggested that horse platelets may be used as a model
      for studying cold-stored platelets. The results are discussed in relation to the
      possible role of phase separation during cell signalling.

PMID- 11302375
TI  - Apoptosis induced in neuronal cells by C-terminal amyloid beta-fragments is
      correlated with their aggregation properties in phospholipid membranes.
AB  - A number of findings suggest that lipophilic monomeric Abeta peptides can
      interact with the cellular lipid membranes. These interactions can affect the
      membrane integrity and result in the initiation of apoptotic cell death. The
      secondary structure of C-terminal Abeta peptides (29-40) and the longer (29-42)
      variant have been investigated in solution by circular dichroism measurements.
      The secondary structure of lipid bound Abeta (29-40) and (29-42) peptides
      prepared at different lipid/peptide ratio's, was investigated by ATR-FTIR
      spectroscopy. Finally, the changes in secondary structure (i.e. the transition of
      alpha-helix to beta-sheet) of the lipid bound peptides were correlated with the
      induction of neurotoxic and apoptotic effects in neuronal cells. The data suggest
      that the C-terminal fragments of the Abeta peptide induce a significant apoptotic
      cell death, as demonstrated by caspase-3 measurements and DNA laddering, with
      consistently a stronger effect of the longer Abeta (29-42) variant. Moreover, the
      induction of apoptotic death induced by these peptides can be correlated with the
      secondary structure of the lipid bound amyloid beta peptides. Based on these
      observations, it is proposed that membrane bound aggregated Abeta peptides
      (produced locally as the result of gamma-secretase cleavage) can accumulate and
      aggregate in the membrane. These membrane bound beta-sheet aggregated amyloid
      peptides induce neuronal apoptotic cell death.

PMID- 11302376
TI  - Structural investigations of pneumolysin/lipid complexes.
AB  - Pneumolysin, a virulence factor from the human pathogen Streptococcus pneumoniae,
      is a water-soluble protein which forms ring-shaped oligomeric structures upon
      binding to cholesterol-containing lipid membranes. It induces vesicle
      aggregation, membrane pore formation and withdrawal of lipid material into non
      bilayer proteolipid complexes. Solid-state magic angle spinning and wideline
      static NMR, together with freeze-fracture electron microscopy, are used to
      characterize the phase changes in fully hydrated cholesterol-containing lipid
      membranes induced by the addition of pneumolysin. A structural model for the
      proteolipid complexes is proposed where a 30-50-meric pneumolysin ring lines the
      inside of a lipid torus. Cholesterol is found to be essential to the fusogenic
      action of pneumolysin.

PMID- 11302377
TI  - Steele v. Hamilton County Community Mental Health Board.

PMID- 11302378
TI  - Promoting research in forensic psychiatry.

PMID- 11302379
TI  - Gay panic.

PMID- 11302380
TI  - Adventures in the twilight zone: empirical studies of the attorney-expert
      relationship.
AB  - A series of empirical pilot studies, performed during workshops at meetings of
      the American Academy of Psychiatry and Law (AAPL), and examining various aspects
      of the attorney-expert witness relationship are presented and their implications
      are discussed. The author calls for further investigation of a topic that-
      although constantly a feature of discussion among both experts and attorneys-
      lacks extensive empirical investigation.

PMID- 11302381
TI  - Perspectives on the divorce process: parental perceptions of the legal system and
      its impact on family relations.
AB  - Through semistructured interviews, divorcing parents provide a consumer
      perspective of the legal process of divorce discussed in law and mental health
      literature. The parents offer a heightened awareness of families' basic needs
      within the legal system that may otherwise be overlooked by professionals. This
      article focuses on narrative accounts provided by 41 divorcing parents to
      describe both their positive and negative experiences with the legal system and
      court-related professionals. Although many parents entered the divorce process
      with hopes for a fair and reasonable experience and outcome, only 12 percent of
      the parents ended the process with positive expectations. Parents conveyed
      feelings of a lack of power and control over divorce outcomes. The responses from
      parents provide valuable insight into how reforms of the legal system can be
      structured best to increase the quality of the process and ameliorate potentially
      destructive effects of divorce on the family.

PMID- 11302382
TI  - Commentary: A rose of a different color.

PMID- 11302383
TI  - The psychologically vulnerable witness: an emerging forensic consulting role.
AB  - The role of witness consultant is emerging as forensic psychiatrists and
      psychologists provide valuable input as participants in witness development
      teams. Anecdotally, retained experts also have undertaken a witness consultant
      role when asked or pressured to do so by the retaining attorney. Forensic
      psychiatrists and psychologists with extensive treatment and testimony experience
      may be of assistance to attorneys in preparing psychologically vulnerable clients
      and nonparty witnesses to tell their stories effectively at trial. In addition to
      litigation, other venues of witness consultation include administrative,
      congressional, and state legislative proceedings. In litigation, the witness
      consultant works directly with the attorney in support of the attorney's
      counselor role with the client. As an agent of the attorney, the identity of the
      witness consultant is shielded by the attorney-client privilege. The witness
      consultant does not meet face to face with the witness unless otherwise
      indicated. Collateral sources of information are used in providing witness
      consultation. The witness consultant can identify and provide management
      techniques for the psychological issues that threaten to impair a witness's
      ability to testify effectively. The consultant also may be able to assist the
      attorney who is experiencing difficulty in his or her relationship with a client
      or a nonparty witness.

PMID- 11302384
TI  - Commentary: Psychiatric consultation on witness preparation.

PMID- 11302385
TI  - Commentary: Role conflict for the witness consultant.

PMID- 11302386
TI  - Antipsychotic prescribing patterns in the Texas prison system.
AB  - Although prison inmates are reported to exhibit elevated rates of psychotic
      disorders, little is known about antipsychotic pharmacotherapy in correctional
      settings. Therefore, the purpose of this study is to describe antipsychotic
      prescribing patterns in one of the nation's largest prison systems. The study
      population consisted of 3,750 Texas Department of Criminal Justice (TDCJ) inmates
      diagnosed with schizophrenic disorders, nonschizophrenic psychotic disorders, or
      both. In 1998, among inmates diagnosed with schizophrenic disorders, 14.6 percent
      were prescribed atypical antipsychotic agents, and 85.4 percent were prescribed
      typical antipsychotic agents. Among inmates diagnosed with nonschizophrenic
      psychotic disorders, 89.3 percent were prescribed typical antipsychotic agents,
      while 10.7 percent were prescribed atypical antipsychotic agents. Black males and
      females were prescribed atypical antipsychotic agents less frequently than their
      counterparts. Understanding such prescribing patterns is integral to the
      efficient and cost-effective planning of correctional mental health care.

PMID- 11302387
TI  - Commentary: Antipsychotic prescribing practices in the Texas prison system.

PMID- 11302388
TI  - Psychiatric expertise in the sentencing phase of capital murder cases.
AB  - The role of forensic psychiatry in the sentencing phase of capital murder cases
      continues to attract intense attention in the psychiatric and legal professions
      as well as in the public eye. Such cases are high stakes, placing psychiatric
      experts under intense scrutiny. Issues of professional identity, roles, and
      ethics arise in capital cases, highlighting the increased psychiatric complexity
      and need for psychiatric expertise. This article will highlight these issues in
      the context of recent state (Texas) appellate and federal court rulings. The
      increased use of capital punishment and the need for increased psychiatric
      expertise in the sentencing phase of capital cases possesses important
      educational and ethics issues for our profession in its "quest for excellence."

PMID- 11302389
TI  - Risk assessment and release decision-making: toward resolving the great debate.

PMID- 11302390
TI  - Measuring level of function in mentally III prison inmates: a preliminary study.
AB  - The need to portray accurately the level of functioning and severity of
      psychiatric symptoms among mentally ill offenders (MIOs) is paramount from
      several perspectives. The prison environment may cast aspersions on the
      reliability and validity of commonly used functional assessment tools. In
      addition, these tools do not capture environment-specific areas that may be of
      interest to the courts, clinicians, community mental health centers, and other
      correctional facilities. Male MIOs (n = 61) who had been treated for at least
      three months in a (male) Washington state prison mental health program were
      evaluated using clinical assessment tools, data abstraction from medical records,
      and structured assessments from correctional officers. Clinical assessments
      occurred at their current site of incarceration. The semistructured clinical
      assessments had high construct validity and correlation for psychiatric symptoms
      and diagnosis. The ability of evaluators to determine accurately relative
      treatment compliance within the prison was low compared with the reports from
      correctional staff, particularly with respect to attendance at programs. In
      general, the officers did not recognize lack of program participation and
      reclusive behavior as potential signs of mental illness. Despite a significant
      history of psychiatric symptoms severe enough to warrant inpatient treatment, 70
      percent of the MIO individuals were functioning reasonably well in a general
      population. A fully informed functional assessment of MIOs likely requires input
      from both clinicians and correctional officers.

PMID- 11302391
TI  - The rise and fall of forensic hypnosis in criminal investigation.

PMID- 11302392
TI  - Personal questions on cross-examination: a pilot study of expert witness
      attitudes.

PMID- 11302393
TI  - False prediction of future dangerousness: error rates and psychopathy checklist-
      revised.

PMID- 11302394
TI  - Race and spiritualism: facing death row--a movie review of The Green Mile.

PMID- 11302395
TI  - Current source density analysis of CNV during temporal gap paradigm.
AB  - The present report studied the contingent negative variation during Gap and Non
      Gap conditions using visual stimulation and manual responses. The reaction times
      during the Gap condition were facilitated compared with those of the Non-Gap
      condition. The contingent negative variation component was obtained during the
      preparatory period from electrodes placed at 58 scalp sites for both Gap and Non
      Gap conditions. The comparison between both conditions: Gap and non-gap did not
      show statistically significant differences during the preparatory period. The
      topography of the voltage and current source density maps showed three different
      foci: (i) an early negativity centred in electrodes overlying the supplementary
      motor area and cingulate motor areas, (ii) an activation over the primary motor
      cortex contralateral to the finger movement, and (iii) a bilateral activation on
      posterior sites. All these results suggest that the facilitation induced by the
      warning stimuli occurs in neural circuits that would be recruited for the
      subsequent processing of the imperative stimulus. The facilitation of the
      reaction times during the gap condition with respect to non-gap condition must be
      justified by neural events occurring during the gap period.

PMID- 11302396
TI  - Multiple dipole analysis of visual event-related potentials during oddball
      paradigm with silent counting.
AB  - In order to cope with the non-uniqueness of multiple equivalent current dipole
      source (ECD) solutions, a priori knowledge about P300 generators of visual event
      related potentials (ERPs) during an oddball paradigm with silent counting task
      was incorporated into the multiple ECD localization method. Four-ECD solutions
      for the target P300 were selected which had the left frontal ECD. The rest of the
      ECDs were localized to the inferior parietal lobule, the hippocampal formation
      and subcortical region. By comparing the present results with those on the visual
      ERPs with button-pressing task, the P300 dipoles common to both the tasks were
      located at the frontal cortices, the hippocampal formation and the thalamus,
      suggesting that these structures are the main P300 generators.

PMID- 11302398
TI  - Spatio-temporal current density reconstruction (stCDR) from EEG/MEG-data.
AB  - Among the different approaches to the bioelectromagnetic inverse problem, the
      current-density reconstruction methods (CDR) provide the most general solutions.
      Since the inverse problem does not have a unique solution, model assumptions have
      to be taken into account. Multi-channel measurements contain not only spatial,
      but also temporal information about the sources, so a naturally extension to
      existing methods leads to spatio-temporal model constraints. Spatio-temporal
      CDR's (stCDR) have been tested in simplified volume conductor models, assuming
      different spatial model constraints and a smooth temporal activation model.
      Comparison to existing spatial model constraints showed a significant improvement
      of spatial and temporal resolution of the reconstructed sources for the spatio
      temporal models especial in noisy data.

PMID- 11302397
TI  - Brain electrical activity evoked by mental formation of auditory expectations and
      images.
AB  - Evidence for the brain's derivation of explicit expectancies in an ongoing
      sensory context has been well established by studies of the P300 and processing
      negativity (PN) components of the event-related potential (ERP). "Emitted
      potentials" generated in the absence of sensory input by unexpected stimulus
      omissions also exhibit a P300 component and provide another perspective on
      patterns of brain activity related to the processing of expectancies. The studies
      described herein extend earlier emitted potential findings in several aspects.
      First, high-density (128-channel) EEG recordings are used for topographical
      mapping of emitted potentials. Second, the primary focus is on emitted potential
      components preceding the P300, i.e. those components that are more likely to
      resemble ERP components associated with sensory processing. Third, the dependence
      of emitted potentials on attention is assessed. Fourth, subjects' knowledge of
      the structure of an auditory stimulus sequence is modulated so that emitted
      potentials can be compared between conditions that are identical in physical
      aspects but differ in terms of subjects' expectations regarding the sequence
      structure. Finally, a novel task is used to elicit emitted potentials, in which
      subjects explicitly imagine the continuations of simple melodies. In this task,
      subjects mentally complete melodic fragments in the appropriate tempo, even
      though they know with absolute certainty that no sensory stimulus will occur.
      Emitted potentials were elicited only when subjects actively formed expectations
      or images. The topographies of the initial portion of the emitted potentials were
      significantly correlated with the N100 topography elicited by corresponding
      acoustic stimuli, but uncorrelated with the topographies of corresponding silence
      control periods.

PMID- 11302399
TI  - A minimal product method and its application to cortical imaging.
AB  - In order to reduce the spatial blurring effect due to the head volume conductor,
      cortical imaging technique (CIT) can be used to reconstruct the cortical
      potential distribution from the scalp potential measurement with enhanced spatial
      resolution. To overcome the ill-posed nature of the inverse problem, Tikhonov
      regularization (TIK) and truncated Singular Value Decomposition (TSVD) are
      commonly used by choosing the appropriate regularization parameter and truncation
      parameter, respectively. We have developed a minimal product method (MINP) to
      determine the regularization and truncation parameters. The present computer
      simulation and experimental results indicate that the MINP can be easily
      implemented in both TIK and TSVD with satisfactory performance, and suggest the
      potential applications of the MINP method in determining the corner of the L
      curve.

PMID- 11302400
TI  - Improvement of source localization by dynamical systems based modeling (DSBM).
AB  - Recently, we have proposed a new concept for analyzing EEG/MEG data (Uhl et al.
      1998), which leads to a dynamical systems based modeling (DSBM) of
      neurophysiological data. We report the application of this approach to four
      different classes of simulated noisy data sets, to investigate the impact of DSBM
      filtering on source localization. An improvement is demonstrated of up to above
      50% of the distance between simulated and estimated dipole positions compared to
      principal component filtered and unfiltered data. On a noise level on which two
      underlying dipoles cannot be resolved from the unfiltered data, DSBM allows for
      an extraction of the two sources.

PMID- 11302401
TI  - Serum concentrations of cefuroxime after continuous infusion in coronary bypass
      graft patients.
AB  - OBJECTIVE: To describe the serum concentrations of continuous infusion of
      cefuroxime for postsurgical prophylaxis of sternal wound infection in patients
      undergoing coronary artery bypass graft (CABG), and to assess the incidence of
      sternal wound infection in this population. METHODS: This was a prospective,
      noncomparative trial involving 54 patients undergoing elective CABG surgery. All
      patients enrolled in the study received cefuroxime 1.5 g as a single intravenous
      dose 30 minutes preoperatively, followed by a continuous infusion of 3 g every 24
      hours until removal of all central venous catheters. RESULTS: Of the 53 evaluable
      patients, the mean steady-state cefuroxime serum concentration was 21.6 +/- 14.2
      microg/mL (range 6.56-59.5). No patient developed a sternal wound infection. The
      mean treatment duration was 2.58 +/- 2.13 days (range 1-13). The median hospital
      and intensive care unit lengths of stay were six days and 46 hours, respectively.
      The average antibiotic cost per day was $32.76. CONCLUSIONS: These preliminary
      results of continuous infusion of cefuroxime 3 g/d for prophylaxis of sternal
      wound infections in CABG patients indicate that serum concentrations are highly
      variable, but reliably above the minimum inhibitory concentration for the common
      anticipated pathogens in this setting. Further comparative trials in a larger
      number of patients are necessary before this mode of administration can be
      routinely advocated for prophylaxis.

PMID- 11302402
TI  - Gastrostomy tube placement in nonadherent HIV-infected children.
AB  - OBJECTIVE: To determine the benefits of gastrostomy tube (G-tube) placement in
      HIV-infected children receiving highly active antiretroviral therapy (HAART).
      METHODS: Children who had a G-tube placed due to medication adminsitration
      difficulties were followed to determine changes in medication adherence and
      changes in laboratory parameters. Medication adherence and laboratory parameters
      were reviewed for three months prior to G-tube placement and then were followed
      for six months after G-tube placement. Viral RNA and CD4+ counts were assessed
      between the two time periods. Medication adherence was followed by review of
      pharmacy refill records and pill counts. Parents were surveyed about their
      opinion regarding the G-tube placement and medication administration in their
      children. RESULTS: Six children had G-tubes placed due to medication
      administration difficulties. The G-tube was tolerated in all six cases, although
      one child developed a staphylococcal infection 13 months after G-tube placement.
      Before G-tube placement, the medication adherence to HAART averaged 47% +/- 20%
      SD, with a range of 15-90%. After G-tube placement, medication adherence improved
      to 90-100%. All parents were satisfied with the G-tube and all reported shorter
      medication administration times and fewer behavioral problems. Five of six
      patients had at least a 2-log10 decrease in viral load, and CD4+ percentages
      improved by an average of 6.4%. CONCLUSIONS: G-tubes were well tolerated by HIV
      infected children. Although G-tube placement is not needed in most children with
      HIV, it may provide an option for parents and children where administration of
      antiretroviral medication poses extreme difficulty and all other avenues have
      been exhausted.

PMID- 11302403
TI  - Antidepressant prescribing to Hispanic and non-Hispanic white patients in primary
      care.
AB  - OBJECTIVE: To examine whether there was a difference in the prescribing of
      selective serotonin-reuptake inhibitors (SSRIs) and non-SSRI antidepressants to
      Hispanic and non-Hispanic white patients in primary care. METHODS: Twenty-seven
      family practice and internal medicine resident physicians and 407 of their
      Hispanic and non-Hispanic white patients who were fluent in English or Spanish
      participated in the study The medical records of all patients were reviewed and
      information about patient diagnoses and antidepressant prescriptions was
      abstracted. Logistic regression was used to examine whether Hispanic ethnicity
      influenced physician prescribing of SSRI and non-SSRI antidepressants while
      controlling for other patient characteristics and diagnoses. For patients with a
      diagnosis of depression, logistic regression was used to examine whether Hispanic
      ethnicity influenced whether patients received antidepressant treatment while
      controlling for other patient characteristics RESULTS: Twenty-seven percent of
      patients received a prescription for one or more antidepressants. Hispanic and
      non-Hispanic white patients were equally likely to be prescribed SSRI and non
      SSRI antidepressant medications. Having a diagnosis of depression and having a
      diagnosis of chronic pain was significantly correlated with the prescribing of a
      non-SSRI antidepressant (p < 0.001, p < 0.01, respectively). Having a diagnosis
      of depression was significantly correlated with the prescribing of an SSRI
      antidepressant (p < 0.001). Hispanic and non-Hispanic white patients with a
      diagnosis of depression were equally likely to be prescribed antidepressant
      treatment. Patients with a diagnosis of depression in the general medicine clinic
      were significantly less likely to receive antidepressant therapy than patients in
      the family practice clinic. CONCLUSIONS: Hispanic ethnicity did not influence
      antidepressant prescribing. Future research in other settings is needed to
      further determine whether Hispanic ethnicity influences antidepressant
      prescribing.

PMID- 11302404
TI  - Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5
      and H.
AB  - OBJECTIVE: To report a case of eosinophilic pleuropericarditis resulting from
      concomitant use of vitamins B5 and H. CASE SUMMARY: A 76-year-old white woman was
      admitted to the hospital because of chest pain and dyspnea related to pleurisy
      and a pericardial tamponade. This patient had no history of allergy and had been
      taking vitamins B5 and H for two months. Blood tests performed showed an
      inflammatory syndrome and a high eosinophil concentration (1200-1500 cells/mm3).
      Pleurocentesis and pericardiotomy yielded a sterile exudative fluid with an
      eosinophilic infiltrate. There were no nuclear antibodies and no rheumatic
      factor; screenings for viruses, parasites, bacteria, and malignant tumor were
      negative. A myelogram, biopsy of the iliac crest bone, and concentration of
      immunoglobulin E were also normal. After withdrawal of the vitamins, the patient
      recovered and the eosinophilia disappeared. DISCUSSION: Prolonged
      hypereosinophilia has marked predilection to damage specific organs, including
      the heart, but pleuropericardial effusion is uncommon. Drug-related
      pleuropericarditis usually occurs without an increased eosinophil count. Other
      drugs responsible for eosinophilic pleuropericarditis are cephalosporins,
      dantrolene, propylthiouracil, and nitrofurantoin. To our knowledge, this is the
      first case report of pleuropericarditis related to vitamins B5 and H.
      CONCLUSIONS: This case suggests that vitamins B5 and H may cause symptomatic,
      life-threatening, eosinophilic pleuropericarditis. Physicians prescribing these
      commonly used vitamins should be aware of this potential adverse reaction.

PMID- 11302405
TI  - Gabapentin for treatment of behavioral and psychological symptoms of dementia.
AB  - OBJECTIVE: To report the use of gabapentin in the treatment of behavioral and
      psychological symptoms of dementia (BPSD) and to review the available literature
      relating to the use of gabapentin in this population. CASE SUMMARY: A 62-year-old
      white man was admitted to the hospital due to a worsening state of confusion,
      anxiety, depressed mood, insomnia, and verbal and physical aggressiveness toward
      his wife. He had a past medical history significant for vascular dementia. He had
      been intolerant of or had failed to respond to numerous antidepressants,
      benzodiazepines, and neuroleptics. The addition of gabapentin to the patient's
      medication regimen resulted in reduced agitation, sexual inappropriateness, and
      lability. He was discharged to his home on a dose of gabapentin 300 mg three
      times daily. DATA SOURCES: A MEDLINE search (1966-August 2000) was performed to
      identify case reports and clinical trials discussing the efficacy of gabapentin
      in the treatment of BPSD. DISCUSSION: Gabapentin, like other anticonvulsants, has
      been used with success in several psychiatric illnesses. Available literature
      indicates that the drug may have some efficacy in the treatment of BPSD. It has a
      favorable adverse effect profile in the elderly, which makes it an attractive
      altemative to standard therapies, including benzodiazepines and neuroleptics.
      Optimal dosing remains unclear. CONCLUSIONS: This case suggests that gabapentin
      is a reasonable alternative therapy for patients whose behavioral symptoms do not
      respond to conventional agents.

PMID- 11302406
TI  - Fluconazole-induced torsade de pointes.
AB  - OBJECTIVE: To present a case of fluconazole-associated torsade de pointes (TDP)
      and discuss fluconazole's role in causing TDP. CASE SUMMARY: A 68-year-old white
      woman with Candida glabrata isolated from a presacral abscess developed TDP eight
      days after commencing oral fluconazole The patient had no other risk factors for
      TDP, including coronary artery disease, cardiomyopathy, congestive heart failure,
      and electrolyte abnormalities There was a temporal association between the
      initiation of fluconazole and TDP. The TDP resolved when fluconazole was
      discontinued; however, the patient continued to have premature ventricular
      contractions and nonsustained ventricular tachycardia (NSVT) until six days after
      drug cessation DISCUSSION: Use of the Naranjo probability scale indicates a
      probable relationship between the use of fluconazole and the development of TDP.
      The possible mechanism is depression of rapidly activating delayed rectifier
      potassium currents. In our patient, there was no other etiology identified that
      could explain QT prolongation or TDP The complete disappearance of NSVT and
      premature ventricular contractions followed by normalization of QT interval after
      the drug was stopped strongly suggests fluconazole as the etiology. CONCLUSIONS:
      Clinicians should be aware that fluconazole, even at low doses, may cause
      prolongation of the QT interval, leading to TDP. Serial electrocardiographic
      monitoring may be considered when fluconazole is administered in patients who are
      at risk for ventricular arrhythmias.

PMID- 11302407
TI  - Zolpidem for antipsychotic-induced parkinsonism.
AB  - OBJECTIVE: To report a case of antipsychotic-induced parkinsonism that was
      managed with zolpidem. CASE SUMMARY: A 34-year-old white man who had had
      antipsychotic-induced parkinsonism with symptoms of repetitive persistent gross
      tremors of the hands for numerous years was unresponsive to traditional
      antiparkinsonian medications. With the initiation of zolpidem 10 mg four times
      daily, the tremors decreased significantly. DISCUSSION: The use of zolpidem for
      antipsychotic-induced parkinsonian hand tremors in this patient was based on the
      severity of the symptoms and the lack of response to several trials of
      traditional medications. When zolpidem was started at 10 mg four times a day, the
      motor examination score on the Unified Parkinson's Disease Rating Scale decreased
      from 29 at baseline to a score of 9 after one month of use. After four months of
      zolpidem use, the patient's mental status decompensated, and clozapine was
      initiated. As the patient experienced excessive sedation, zolpidem was
      discontinued while clozapine was maintained to help with the psychosis and,
      potentially, the tremors. The tremors reemerged with a motor examination score of
      30. Zolpidem was reinitiated at 5 mg four times daily, and the patient's tremors
      have been stable for two years. CONCLUSIONS: Further investigation is needed to
      study the use of nontraditional medications in patients requiring antipsychotic
      medications who have refractory parkinsonian symptoms.

PMID- 11302408
TI  - Gynecomastia associated with highly active antiretroviral therapy.
AB  - OBJECTIVE: To report four cases of HIV-associated gynecomastia diagnosed during
      treatment with nucleoside analogs with or without protease inhibitors. CASE
      SUMMARY: Four HIV-infected patients developed gynecomastia while taking two
      nucleoside analogs (stavudine combined with lamivudine in 3 patients, stavudine
      with didanosine in 1 patient) and protease inhibitors (indinavir, nelfinavir,
      ritonavir-saquinavir in 3 patients) all patients had received prior treatment
      with single or associated nucleoside analogs for > or = 21 months. Gynecomastia
      occurred three to seven months after the start of a triple regimen in the first
      three patients, and 17 months after initiating the last dual nucleoside analog
      therapy in the remaining patient. Liver, kidney, and thyroid function were
      normal; a routine endocrinologic workup showed slight follicle-stimulating
      hormone and luteinizing hormone abnormalities in one patient only. Other possible
      causes of drug- or disease-induced gynecomastia were excluded. A concurrent fat
      redistribution syndrome was present in three patients (including the patient who
      received nucleoside analogs only), while serum lipid and/or glucose concentration
      abnormalities were present in all patients. Gynecomastia remained unchanged
      during the subsequent seven- to 16-month follow-up, even after modification of
      antiretroviral therapy. DISCUSSION: Gynecomastia has been recently associated
      with antiretroviral therapy, and all reported cases but one occurred two to 17
      months after the start of a protease inhibitor-based regimen. Our experience
      underlines the possible occurrence of gynecomastia in the absence of protease
      inhibitor administration, its persistence despite changes of antiretroviral
      regimen (thus resembling some signs related to lipodystrophy syndrome), and the
      apparently constant association with prolonged nucleoside analog administration
      (especially stavudine). CONCLUSIONS: Gynecomastia should be included among
      emerging adverse effects of antiretroviral therapy, although its etiopathogenesis
      deserves further investigation.

PMID- 11302409
TI  - Argatroban for prevention and treatment of thromboembolism in heparin-induced
      thrombocytopenia.
AB  - OBJECTIVE: To renew the pharmacology, pharmacokinetics, efficacy adverse events,
      and cost of argatroban in the prevention and treatment of thromboembolism in
      patients with heparin-induced thrombocytopenia (HIT). DATA SOURCES: A MEDLINE
      search (1980 to August 2000) of English-language literature was conducted using
      the search term argatroban to identify pertinent case reports, clinical trials,
      abstracts, and review articles. Additional reports were identified from the
      reference lists compiled in the literature reviewed, as well as from the
      manufacturer. DATA SYNTHESIS: Argatroban is a synthetic direct thrombin inhibitor
      indicated for parenteral use in the prevention and treatment of thromboembolism
      in patients with HIT. Its elimination half-life is approximately 40-50 minutes,
      and it is primarily eliminated by hepatic metabolism and biliary secretion.
      Compared with historical controls, argatroban-treated patients with HIT or HIT
      with thrombosis (HITTS) experienced lower rates of the composite end point of
      death, amputation, and new thrombosis. Dosing is initiated at 2 microg/kg/min and
      adjusted to maintain the activated partial thromboplastin time at 1.5-3 times the
      patient's baseline. In Japan, argatroban is approved for use in acute ischemic
      stroke and chronic peripheral occlusive disease. It has also been used as an
      alternative to unfractionated heparin (UFH) in patients with a history of HIT or
      HITTS undergoing percutaneous coronary intervention and other procedures.
      Additionally, argatroban has been compared with UFH in patients with acute
      myocardial infarction who were receiving thrombolytic therapy. Hemorrhage is the
      primary adverse event associated with argatroban. Argatroban increases the
      prothrombin time, making assessment of the intensity of warfarin therapy during
      concurrent administration more complex. CONCLUSIONS: The use of argatroban in
      patients with HIT and HITTS is associated with improvement in clinical outcomes
      compared with historical controls. Argatroban offers several practical advantages
      over other available agents with respect to dosing, monitoring, reversibility of
      effect with discontinuation of the drug, and cost.

PMID- 11302410
TI  - Slowing the progression of renal disease in diabetic patients.
AB  - OBJECTIVE: To review recent clinical trials that evaluate the most appropriate
      therapeutic options for delaying the progression of nephropathy in type 2
      diabetic patients. DATA SOURCES: Primary and review articles were retrieved
      through a MEDLINE search (January 1990-January 2000). STUDY SELECTION AND DATA
      EXTRACTION: All studies related to attenuating the progression of nephropathy in
      diabetic patients were evaluated and included in this review. DATA SYNTHESIS:
      Clinical trials with angiotensin-converting enzyme inhibitors (ACEI) have
      consistently demonstrated a decrease in the progression of renal disease in
      diabetic patients. The angiotensin-2 receptor blocker (ARB) losartan has been
      shown to reduce microalbuminuria to the same extent as the ACEI enalapril. The
      nondihydropyridine calcium-channel blockers (NCCBs) verapamil and diltiazem have
      also been shown to decrease urinary albumin excretion. Clinical literature
      suggests that if monotherapy with an ACEI or ARB does not provide an adequate
      response, an NCCB should be added to the regimen. CONCLUSIONS: ACEIs should be
      considered first-line therapy for diabetic patients with nephropathy. ARBs should
      be considered as an alternative for patients who are unable to tolerate an ACE
      inhibitor due to adverse effects. If blood pressure goals are not achieved with
      an ACEI or ARB, then the addition of an NCCB should be considered.

PMID- 11302411
TI  - Etanercept in juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To review the classification, pathophysiology, safety, and efficacy of
      treatment options for juvenile rheumatoid arthritis (JRA). Etanercept, the agent
      most recently approved by the Food and Drug Administration for use in JRA, is
      featured. DATA SOURCES: Articles were identified from a search of the MEDLINE
      database (1966 to January 2000) and through secondary sources. Meeting abstracts
      and posters were also evaluated. STUDY SELECTION AND DATA EXTRACTION: Articles
      identified and retrieved from data sources were evaluated and, if determined to
      be relevant, were included in this review. DATA SYNTHESIS: JRA represents a major
      cause of functional disability in children. In contrast to traditional
      therapeutic agents for JRA, which act through generalized antiinflammatory
      activity or generalized immunosuppression, new therapeutic modalities have been
      developed that target specific molecules involved in the pathophysiology of JRA.
      Etanercept inhibits the activity of tumor necrosis factor and lymphotoxin-alpha.
      In a clinical trial of patients with polyarticular-course JRA, etanercept-treated
      patients experienced less pain and swelling in their joints, decreased incidence
      of disease activity, less frequent flare, and a longer time to flare than
      patients receiving placebo. Treatment with etanercept was generally well
      tolerated. CONCLUSIONS: Etanercept represents an exciting new therapeutic option
      for the treatment of JRA. The positioning of etanercept among other therapeutic
      options for JRA will be more clearly established as additional safety and
      efficacy data are made available.

PMID- 11302412
TI  - Risks and benefits of glycoprotein IIb/IIIa antagonists in acute coronary
      syndrome.
AB  - BACKGROUND: Recommendations for the use of glycoprotein (GP) IIb/IIIa antagonists
      should consider not only their effectiveness but also their links with other
      clinical findings (both favorable and adverse), the risk/benefit ratio in
      different subgroups of patients, and the existence of other therapeutic
      alternatives; additionally, the estimates underlying the recommendation should be
      explicit. OBJECTIVE: To establish explicit evidence-based recommendations
      regarding the use of GP IIb/IIIa antagonists in medically treated patients with
      acute coronary syndrome without ST-segmentelevation. DATA SOURCES: MEDLINE-based
      search (1980 to November 1999) of randomized controlled trials for effectiveness
      data and nonsystematic review of published data regarding utilities of relevant
      status and clinical events. STUDY SELECTION: We included clinical trials in which
      the patients were randomly assigned either to an experimental group treated with
      intravenous GP IIb/IIIa antagonists or to a control group. We excluded studies in
      which the intention to perform a percutaneous procedure was a criterion for
      inclusion. DATA EXTRACTION: The effectiveness of the treatment was defined as the
      incidence of death or a nonfatal infarct at 30 days. The risks of the treatment
      were estimated using the incidence of moderate to severe hemorrhage. DATA
      SYNTHESIS: Meta-analysis of randomized controlled trials in patients with acute
      coronary syndrome and calculation of the threshold number needed to treat (t
      NNT). RESULTS: Compared with conventional treatment, GP IIb/IIIa antagonists
      reduce the risk of death or nonfatal infarct at 30 days by approximately 11.7%
      (number needed to treat [NNT] = 65 for the basal risk of patients included in the
      studies; 95% CI 40 to 203). However, the use of GP IIb/IIIa antagonists increases
      the risk of moderate to severe hemorrhage by 32%. In an analysis biased in favor
      of the use of GP IIb/IIIa antagonists, these risks imply a t-NNT of approximately
      150, which overlaps with the confidence interval of the basal NNT. The limits of
      a 95% confidence interval of the NNT are only lower than the t-NNT in patients
      with a high risk of death/infarct (at least 5%) and low risk of hemorrhage (less
      than the weighted basal risk in the trials analyzed). CONCLUSIONS: At present,
      there is no conclusive evidence that the expected benefits outweigh the nsks in
      the average patient included in the available trials. The benefit is probably
      greater than the risks in patients with a high risk of death/infarct and low risk
      of hemorrhage. In patients with a low risk of death/infarct and/or high risk of
      hemorrhage, the risks seem to outweigh the benefits and so, in the latter case,
      such therapy should not be used.

PMID- 11302413
TI  - Pneumococcal resistance: the treatment challenge.
AB  - OBJECTIVE: To review in vitro and in vivo information dealing with pneumococcal
      antibiotic resistance and provide a review of the incidence, mechanisms, and
      controversies surrounding this growing problem. The review is also intended to
      provide clinicians with relevant recommendations on treatment and prevention of
      this organism. DATA SOURCES AND SELECTION: Primary and review articles were
      identified by MEDLINE search (1966-August 2000) and through secondary resources
      such as conference proceedings. All of the articles identified from the data
      sources were evaluated, and all information deemed relevant was included in this
      review. DATA SYNTHESIS: The growing incidence and reporting of pneumococcal
      isolates that are resistant to one or more classes of antibiotics have become a
      troubling trend that has resulted in significant shifts in treatment. Although
      clinicians have shifted to a new generation or class of antibiotics when faced
      with a resistance trend, data with resistant pneumococci show that this may not
      be necessary. By incorporating the pharmacokinetic and pharmacodynamic data of
      antimicrobials into the decision-making process, many of the drugs that we have
      become hesitant to use due to this resistance may still be appropriate if used
      correctly. CONCLUSIONS: Appropriate dosing of antimicrobials, combined with
      optimal use of pneumococcal vaccines, will not only prolong the longevity of some
      agents, but also hopefully slow resistance development.

PMID- 11302414
TI  - Mood disorders associated with interferon treatment: theoretical and practical
      considerations.
AB  - OBJECTIVE: To review the theoretical and clinical aspects of mood disorders
      associated with interferon treatment and discuss their management. DATA SOURCES:
      Pertinent and selected laboratory/clinical studies, review articles, letters,
      abstracts, and book chapters on behavioral and mood-related adverse effects of
      interferons published in English-language journals in the past two decades were
      identified by MEDLINE (June 1980-June 2000) and manual searches. DATA SELECTION
      AND DATA EXTRACTION: All of the publications identified were reviewed, and the
      relevant data were included. Studies not using criteria for psychiatric diagnosis
      or instruments for psychiatnc monitoring were excluded. DATA SYNTHESIS: Clinical
      observations and limited research data suggest that interferon treatment may be
      associated with mood disorders. Mood-related symptoms induced by interferons
      emerge in a few days or weeks and tend to be dose dependent. Their severity may
      necessitate discontinuation of interferon therapy and/or the use of
      antidepressant or antimanic agents. The mechanisms responsible for inducing or
      exacerbating mood disorders in interferon-treated patients have not been
      elucidated. There is limited evidence implicating alterations in the serotonin
      system. CONCLUSIONS: While interferon therapy may trigger or induce mood-related
      symptoms, preexisting or stable concurrent mood disorders in remission do not
      necessarily constitute a contraindication to treatment with interferons. Mood
      disorders associated with interferon treatment can present clinical challenges.
      However, they may promote our understanding of mood disorders in the context of
      the current biologic theories of depression and mania.

PMID- 11302415
TI  - Alternate-day dosing of HMG-CoA reductase inhibitors for cholesterol reduction.
AB  - OBJECTIVE: Assess efficacy, safety, and cost of alternate-day dosing with 3
      hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (HRIs). DATA:
      International Pharmaceutical Abstracts and MEDLINE (English-language clinical
      trials, 1966-April 2000) were searched. DATA SYNTHESIS: Established efficacy of
      HRIs is based on daily administration. Many patients who could benefit from these
      agents are unable to afford them; therefore, alternate-day dosing may be a
      solution for reducing expense without decreasing therapy benefits. Studies
      addressing alternate-day HRI therapy are evaluated to determine the usefulness of
      this option for cholesterol reduction. CONCLUSIONS: Although limited studies
      imply a trend toward benefit with alternate-day HRI therapy, large, controlled,
      randomized trials are needed before making this a standard recommendation.

PMID- 11302416
TI  - Interaction between warfarin and danshen (Salvia miltiorrhiza).
AB  - OBJECTIVE: To discuss the potential for an adverse interaction between the
      Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhiza Bge, and
      warfarin. DATA SOURCES: A MEDLINE search was performed (from January 1966 through
      October 2000) using the key words danshen and Salvia miltiorrhiza. All articles
      written in English or with an English extract were considered for review. STUDY
      SELECTION AND DATA EXTRACTION: All studies of antithrombotic effects of danshen
      or interaction between danshen and warfarin were evaluated. Previous case reports
      of an adverse interaction between danshen and warfarin were reviewed. DATA
      SYNTHESIS: Danshen is commonly used in mainland China for the treatment of
      atherosclerosis-related disorders such as cardiovascular and cerebrovascular
      diseases. Danshen can affect hemostasis in several ways, including inhibition of
      platelet aggregation, interference with the extrinsic blood coagulation,
      antithrombin III-like activity, and promotion of fibrinolytic activity. Single
      dose and steady-state studies in rats indicated that danshen increased the
      absorption rate constants, AUCs, maximum concentrations, and elimination half
      lives, but decreased the clearances and apparent volume of distribution of both R
      and S-warfarin. Consequently, the anticoagulant response to warfarin was
      exaggerated. Three cases have previously been published reporting gross
      overanticoagulation and bleeding complications when patients receiving chronic
      warfarin therapy also took danshen. CONCLUSIONS: Because of both pharmacokinetic
      and pharmacodynamic interactions, danshen should be avoided in patients taking
      warfarin.

PMID- 11302417
TI  - Systemic adverse effects from topical doxepin cream.

PMID- 11302418
TI  - Comment: other factors should be considered in a possible warfarin and
      sulfasalazine interaction.

PMID- 11302419
TI  - Comment: olanzapine-induced acute pancreatitis.

PMID- 11302420
TI  - Alterations of the pituitary-gonadal axis in the neonatal blue fox (Alopex
      lagopus) exposed to prenatal handling stress.
AB  - Handling is a stressor for blue foxes. The influence of preterm handling (1 min
      daily) of vixens was investigated in 68, 10-day-old cubs, 34 male and 34 female.
      Body, gonadal and pituitary weight, ano-genital distance, gonadal testosterone
      and oestradiol content and in vitro production, and pituitary LH content were
      measured in all cubs. The gonads were frozen or incubated in vitro with, or
      without, added hCG (2.5 IU per sample). The gonadal incubates and homogenates
      were analysed for testosterone and oestradiol by radioimmunoassay and the
      pituitary homogenates for LH by immunofluorometric assay. The results indicate
      that neonatal fox gonads actively produce steroids and that there are significant
      sex differences in basal steroid production and response of the gonads to hCG,
      and in pituitary LH content. Maternal stress resulted in a significant reduction
      of morphometric and hormonal measures of the reproductive system in neonatal blue
      foxes, with more drastic effects in female cubs. Gonadal weights were lower in
      cubs of both sexes from stressed vixens (65.7+/-4.3 v 50.6+/-1.8 mg for the
      ovaries and 23.2+/-1.0 v. 17.7+/-1.0 mg for the testes, control v. stressed
      animals, P<0.01). The ano-genital distance in female offspring of stressed vixens
      was reduced (1.1+/-0.04 v. 0.9+/-0.03 cm, P<0.01). Basal ovarian oestradiol and
      testosterone production were decreased in cubs from prenatally stressed animals
      in comparison with controls (43.5+/-3.5 v. 32.6+/-3.7 pg ovary(-1) h(-1) and
      0.40+/-0.16 v. 0.12+/-0.03 ng ovary(-1) h , P<0.05). Prenatal stress did not
      affect either pituitary weights or LH content in either sex. There were no
      significant differences in ano-genital distance, testicular content of
      testosterone, or in vitro testosterone production between control and treated
      male cubs. In conclusion, these findings suggest that prenatal handling stress
      impaired the neonatal reproductive development of the female offspring, but had
      no marked effects on males. Sex-specific effects of prenatal handling stress on
      the reproductive development in foxes may be linked with the gender differences
      in responses of the hypothalamus-pituitary-adrenocortical axis to stress
      conditions in this species.

PMID- 11302421
TI  - Aetiology of attenuated luteal development in prednisolone-induced eosinopenic
      ewes.
AB  - Eosinophilic leukocytes infiltrate the wall of postovulatory ovine follicles. The
      objective of this investigation was to assess a putative role of resident
      eosinophils in the folliculo luteal transition. Eosinophils accumulated where new
      blood vessels were evident along connective tissue trabeculae that pervaded the
      parenchyma of formative corpora lutea. Mid-phase function of corpora lutea
      (progesterone output) was suppressed in ewes in which eosinophils were ablated by
      systemic administration of prednisolone following ovulation. Glandular
      dysfunction was related to a diminished angiogenic response (quantitative image
      analysis of vascular space in histological specimens and scanning electron
      microscopy of corrosion casts) during the luteinization process. Vascular
      endothelial growth factor (VEGF) was localized by immunofluorescence microscopy
      to luteal eosinophils. It is suggested that VEGF of eosinophilic origin
      contributes to the neovascularization mechanism of corpora lutea in sheep.

PMID- 11302422
TI  - Development of porcine oocytes from preovulatory follicles of different sizes
      after maturation in media supplemented with follicular fluids.
AB  - The development of porcine oocytes from large (3.1-8.0 mm in diameter) or small
      (<3.1 mm) follicles was examined after maturation culture in medium containing
      porcine follicular fluid (pFF). Large follicles yielded larger (256 microm v. 221
      microm; P<0.05) cumulus-oocyte complexes and more (22 v. 14%) morphologically
      normal oocytes than small follicles (Experiment 1). In Experiments 2-4,
      maturation media supplemented with mixed pFF (10%) from small and large follicles
      was used. More oocytes from large follicles matured (58% v. 91%), formed
      pronuclei (81% v. 90%) and developed to the blastocyst stage (2% v. 10%) than
      oocytes from small follicles. In Experiments 5-7, the effects of pFF collected
      from either small or large follicles on oocyte development were examined.
      Regardless of the source of oocytes, large-follicle-derived pFF more
      significantly enhanced preimplantation development than did small-follicle
      derived pFF. The highest rate of blastocyst formation (16%) was found when
      oocytes from large follicles were cultured in maturation medium containing large
      follicle-derived pFF. These results suggest that oocytes from large follicles
      have greater developmental potential than oocytes from small follicles, and that
      the origin of pFF, which is added to the maturation media, might be an important
      factor for improving in vitro development of porcine oocytes.

PMID- 11302423
TI  - Diminished PGE2 content, enhanced PGE2 release and defects in 3H-PGE2 transport
      in embryos from overtly diabetic rats.
AB  - Diminished PGE2 levels in diabetic embryos are related to the development of
      malformations, and thus the aim of the present study was to determine whether
      PGE2 levels are modified in rat embryos cultured in diabetic serum during
      organogenesis, and if PGE2 content and release, and 3H-PGE2 uptake and release,
      are altered in incubated diabetic embryos. Rats were made diabetic by
      steptozotocin (60 mg kg(-1)) before mating. Control rat embryos cultured for 24 h
      (explantation Day 9) in the presence of diabetic serum showed diminished PGE2
      levels. When Day 10 diabetic embryos were incubated, embryo PGE2 levels were
      lower, but the PGE2 released to the incubation media was much higher than in
      controls. Uptake of 3H-PGE2 by diabetic embryos was initially enhanced (5-10
      min), then reached similar levels to controls (20-100 min). Release of 3H-PGE2
      previously incorporated during a 60-min incubation was greater in diabetic
      embryos than in controls. These results show diminished PGE2 content in both
      diabetic and normal embryos cultured in the presence of diabetic serum, but
      suggest that diabetic embryos have the capability to produce and release high
      levels of PGE2. The enhanced release of PGE2 is probably the result of transport
      abnormalities, and leads to the elevated PGE2 concentrations found in the
      incubating medium and to the diminished intraembryonic PGE2 levels that alter
      embryonic development.

PMID- 11302424
TI  - Influences on fetal and placental weights during mid to late gestation in
      prolific ewes well nourished throughout pregnancy.
AB  - This study investigated associations between fetal and placental weights from 85
      to 130 days gestation in 49 fetuses from 21 ewes of a prolific genotype used as
      an experimental model of intrauterine growth retardation. The proportion of
      variation in fetal weight explained by placental weight increased from zero at 85
      days to 91% (residual standard deviation (RSD) = 260 g) at 130 days. Overall,
      stage of pregnancy plus placental weight accounted for 96% of fetal weight
      variation (RSD = 212 g). Litter size and number of fetuses per uterine horn also
      influenced individual fetal weights. Gestational age, litter size, placental
      weight per ewe, and liveweight and condition score of ewes during early to mid
      gestation (initial LW and CS) explained 99.5% of the variation in fetal weight
      per ewe (RSD = 236 g). Most variation (86%) in placental weight was explained by
      stage of pregnancy, litter size, number of placentomes, and initial LW and CS
      (RSD = 53 g). Placental weight per ewe was influenced by stage of pregnancy,
      litter size and initial ewe LW and CS (R2 = 0.97; RSD = 89 g). The association of
      fetal and placental weights with initial ewe LW was positive, and with initial CS
      was negative. The results show that in the absence of overt nutritional
      restriction of pregnant ewes, fetal and placental weights are tightly coupled
      during late gestation and ewe fatness during early pregnancy is inversely related
      to placental and fetal weights. They demonstrate that placental weight explains
      most of the variation in fetal weight in the present intrauterine growth
      retardation model.

PMID- 11302425
TI  - Oxytocin-stimulated phosphoinositide hydrolysis and prostaglandin F2alpha
      secretion by luminal epithelial, glandular epithelial and stromal cells from pig
      endometrium. II. Responses of cyclic, pregnant and pseudopregnant pigs on days 12
      and 16 post oestrus.
AB  - In pigs, the exact mechanism for the shift in endometrial PGF2alpha secretion
      from an endocrine to an exocrine mode during pregnancy recognition is not known.
      The objective of this study was to examine whether this shift involved a change
      in the responsiveness of luminal epithelial, glandular epithelial and stromal
      cells to 0 or 100 nM oxytocin. Luminal epithelial cells, glandular epithelial
      cells and stromal cells were isolated from cyclic, pregnant or oestrogen-induced
      pseudopregnant gilts on Day 12 (Experiment 1) or Day 16 (Experiment 2) post
      oestrus (oestrus = Day 0). For cells obtained on Day 12, oxytocin stimulated
      PGF2alpha secretion by stromal cells (P<0.01) similarly for each reproductive
      status, whereas oxytocin stimulated PGF2alpha secretion from luminal and
      glandular epithelial cells (P<0.05) from pregnant and pseudopregnant gilts but
      not from cyclic gilts. For both concentrations of oxytocin, mean PGF2alpha
      secretion was less (P<0.05) from stromal cells of pregnant than cyclic gilts. For
      cells obtained on Day 16, oxytocin stimulated PGF2alpha release from stromal
      cells of cyclic gilts but not from stromal cells of pregnant gilts. Mean
      PGF2alpha secretion also was less (P<0.05) from stromal cells of pregnant gilts
      than cyclic gilts. Oxytocin tended to stimulate PGF2alpha release (P<0.07) from
      glandular epithelial cells of cyclic but not pregnant or pseudopregnant gilts.
      Luminal epithelial cells from all reproductive statuses were similarly
      unresponsive to oxytocin. In conclusion, the increased PGF2alpha secretory
      response to oxytocin of luminal and glandular epithelial cells from pregnant
      gilts on Day 12, combined with the decreased response of stromal cells from
      pregnant gilts on Days 12 and 16, may contribute, in part, to the shift in
      endometrial PGF2alpha secretion from an endocrine to an exocrine direction during
      early pregnancy in pigs.

PMID- 11302426
TI  - Assessment of learning ability and behaviour in low birthweight lambs following
      intrauterine growth restriction.
AB  - The present study used behavioural tasks to assess learning ability and behaviour
      in postnatal lambs, and to examine the effects of low birthweight (LBW) and age
      on subsequent performance. It was hypothesized that intrauterine growth
      restriction (IUGR) and LBW lead to learning and behavioural deficits in the early
      postnatal period. IUGR and LBW were induced by umbilico-placental embolization
      from 120 days of gestational age (g.a.) to the onset of labour. Behavioural
      studies were performed on 6 LBW and 6 control lambs between 2 and 6 weeks after
      birth. LBW lambs were born at 139+/-1 days g.a. (2.4+/-0.2 kg) and control lambs
      were born at 149+/-1 days g.a. (4.5+/-0.4 kg). Three tasks were used to assess
      the learning ability and behaviour of the lambs: a simple maze, an obstacle
      course, and a T-maze. LBW lambs took longer to complete the simple maze at all
      ages, and made a greater number of errors at Week 1 of testing compared to
      control lambs; the total trial duration and number of errors decreased with age
      for both groups. In the obstacle course, the times taken to complete the first
      and third trials were used for analysis; a decrease in trial time and the number
      of errors from Trial 1 to Trial 3 were indications of the lamb's ability to learn
      how to negotiate the objects within the course. LBW lambs recorded longer trial
      durations for the first trial at Week 5 of testing, and for the third trial at
      Week 4. LBW lambs made more errors for the first trial at Week 5 of testing than
      control lambs. In the T-maze, there was no significant effect of treatment or
      age. It was concluded that differences between the groups may have been the
      result of LBW lambs being prematurely born. The value of these tasks in the
      assessment of learning ability and behaviour in young lambs is discussed.

PMID- 11302427
TI  - Localization and quantitation of hyaluronan and sulfated glycosaminoglycans in
      the tissues and intraluminal fluid of the pig oviduct.
AB  - Glycosaminoglycans (GAGs), hyaluronan (HA) and heparan sulfate (HS) were
      localized in the pre- and post-ovulatory oviducts of inseminated and control (non
      inseminated) sows using biotinylated HA-binding protein (HABP) and anti-syndecan
      antibodies respectively. In addition, the concentrations of HA and total sulfated
      GAGs (S-GAGs) were measured in fluid collected in vivo from either a selected
      tubal segment (isthmus or ampulla) or from the contralateral whole oviduct (WO)
      of non-inseminated sows during proestrus-metoestrus. HA was localized in the
      lamina propria of the entire oviduct, but epithelial HA-labelling was only
      present in the sperm reservoir (uterotubal junction adjacent isthmus) in control
      and inseminated sows. In contrast, immunolabelling for HS proteoglycans (HSPGs,
      syndecans) was present on the entire epithelial lining, both pre and post
      ovulation and in both sow groups. Both HA and S-GAGs could be detected in the
      intraluminal fluid. Concentrations varied among sows and segments; those of the S
      GAGs being higher (P<0.05) than that of HA. Mean levels of S-GAGs and HA tended
      to increase in the fluid collected from isthmus and ampulla during standing
      oestrus. Fluid levels from the WO, however, fluctuated less during the collection
      period. Major statistical differences were not present, owing to the large
      variation seen between animals. The results confirm, however, that GAGs are
      present in the pig oviduct. The conspicuous localization in the sperm reservoir
      and the tendency to higher levels in the fluid during pre-ovulatory oestrus
      support the hypothesis that GAGs play a role in modulating sperm viability and
      capacitation during sperm transport in the pig oviduct.

PMID- 11302428
TI  - A dipstick immunoassay to rapidly measure serum oestrone sulfate concentrations
      in horses.
AB  - A dipstick, competitive immunoassay for rapidly measuring serum oestrone sulfate
      (OS) concentrations in horses was developed to distinguish mares 100 or more days
      pregnant from non-pregnant animals. 6-Ketoestrone 6-carboxymethyloxime conjugated
      to bovine serum albumin (oestrone CMO-BSA) was 'dotted' 25 mm from the bottom
      edge of 45 x 5 mm strips of polyester-film-supported cellulose nitrate membrane,
      pore size 3 microm. The strips were blocked, dried and a 15 x 5-mm cellulose
      absorbent sink attached 10 mm from the top of each strip. The manufactured
      dipsticks were stored with desiccant at room temperature until used. A monoclonal
      antibody recognizing OS was coated onto uniform, blue-dyed polystyrene
      microspheres (mean diameter, 0.31 microm) by adsorption. After blocking, several
      washes and resuspension by sonication, the antibody-coated microspheres were
      stored at 4 degrees C. The concentrations of oestrone CMO-BSA dotted onto the
      dipsticks and OS antibody coated onto the microspheres were optimized to produce
      a test that allowed maximum discrimination between the concentrations of OS found
      in serum of mares 100 or more days pregnant (i.e. >30 ng OS mL(-1)) relative to
      those found in non-pregnant mares (i.e. <10 ng OS mL(-1)). To perform the
      dipstick test, 30 microL of carrier buffer, 10 microL of OS antibody-coated
      microspheres and 10 microl of OS standard or serum sample were pipetted into a
      microwell and mixed. A dipstick was placed in the solution. All the liquid
      migrated up the dipstick into the absorbent sink within 15-20 min leaving a blue
      dot where the OCMO-BSA had been placed. The intensity of colour of the blue dot,
      which correlated inversely with the concentration of OS in the standard or serum
      sample, was assessed visually and by computer image analysis. An OS concentration
      less than 5 ng mL(-1) produced a deep blue dot, 20 ng/ml a light blue dot and a
      concentration greater than 50 ng mL(-1) a very faint blue dot, or none at all.
      Serum samples from 42 non-pregnant mares and 40 mares over 100 days pregnant were
      analysed by the dipstick test. All the serum samples from non-pregnant mares
      produced dipsticks with deep blue dots that ranged in intensity from 20 to 38
      colour intensity units, equivalent to OS concentrations less than 7 ng mL(-1).
      Sera from all the pregnant mares generated dipsticks with either faint blue dots
      or none at all (i.e. < or =5 colour intensity units, equivalent to OS
      concentrations >40 ng mL(-1). It is concluded that this novel, rapid dipstick
      immunoassay offers a practical, alternative means of analysing serum OS
      concentrations in horses, and enables mares that are 100 or more days pregnant to
      be distinguished from those that are not pregnant.

PMID- 11302429
TI  - Screening the foods of an endangered parrot, the kakapo (Strigops habroptilus),
      for oestrogenic activity using a recombinant yeast bioassay.
AB  - In recent years the possibility of environmental oestrogens affecting the
      reproduction of vertebrates has become an issue of both public and scientific
      interest. Although the significance of such chemicals remains controversial there
      is clear evidence that, in some contexts, environmental oestrogens can influence
      the fertility of vertebrates. Highly endangered species represent a situation in
      which even modest reductions in the fertility of key individuals may have
      implications for the survival of the entire species. This paper reports the
      screening of both natural and supplementary foods of the kakapo (Strigops
      habroptilus), a critically endangered New Zealand nocturnal parrot, for
      oestrogenic activity using a recombinant yeast based bioassay. Low levels of
      oestrogenic activity were detected in one of the 'chick-raising' foods, but no
      oestrogenic activity was detected in the adult supplementary foods. The
      oestrogenicity of a range of phytochemicals possibly associated with the kakapo
      natural diet was also examined. Two such phytochemicals, podocarpic acid and its
      reduced derivative podocarpinol, showed weak oestrogenic activity (approximately
      10(-6) and 10(-4) of the activity of 17-beta-oestradiol, respectively).

PMID- 11302430
TI  - Intracellular pH increase accompanies parthenogenetic activation of porcine,
      bovine and murine oocytes.
AB  - Although an intracellular pH (pHi) increase at the time of fertilization is
      necessary for activation of the sea urchin egg, recent reports in the mouse and
      rat have indicated that there is not a pHi increase during fertilization or
      during 7% ethanol activation in the mouse. It has been suggested that mammals may
      have lost the need for a pHi increase at the time of fertilization and the
      present study reports significant pHi changes during parthenogenetic activation
      of porcine IVM oocytes, as well as pHi responses to activation in bovine and
      murine oocytes. Transient intracellular pH changes were found during porcine
      oocyte activation when using 7% ethanol and with 50 or 100 microM calcium
      ionophore (A23187). Treatment with 200 microM thimerosal resulted in an increase
      in pHi after a delay of approximately 12 min. Murine oocytes showed a significant
      increase during activation with 7% ethanol and A23187 as well as during prolonged
      exposure to thimerosal. Bovine oocytes exhibited an increase in pHi only when
      activated with 50 or 100 microM A23187. The final set of experiments aimed to
      determine whether the porcine oocyte has mechanisms to alleviate induced acidic
      and alkaline challenges. Both acidic (approximately 20 mM acetic acid) and
      alkaline (approximately 30 mM ammonium chloride) challenges caused significant
      changes in pHi that porcine IVM oocytes were capable of recovering from within 35
      min. Future studies will focus on determining which of the mechanisms is
      producing the pHi increase at the time of parthenogenetic activation in the
      porcine oocyte.

PMID- 11302431
TI  - Phosphorylation of mitogen-activated protein kinase cascade during early embryo
      development in the mouse.
AB  - The mitogen-activated protein kinase (MAPK) cascade is one of the most important
      signal transduction pathways that regulate the cell cycle in somatic cells. The
      present study examined the phosphorylation states of components in the MAPK
      cascade, Raf-1, MEK-1, and extracellular signal regulated kinases (ERKs), which
      are activated by mitogens, throughout early mouse embryo development and in
      cultured somatic cells generally. In somatic cells, Raf-1 and MEK-1 were
      phosphorylated at M-phase and dephosphorylated during interphase. ERKs were not
      phosphorylated at any stage during the cell cycle. These results were similar to
      previous findings for the first and second cell cycles of early mouse embryos. In
      contrast, after the four-cell stage, not only ERKs, but also Raf-1 and MEK-1,
      were not phosphorylated at any stage during the cell cycle in mouse early
      embryos. These results suggest that the MAPK cascade in mouse embryos is
      regulated by the same mechanism as in somatic cells before the two-cell stage,
      and that regulation is changed to an embryo-specific mechanism after the four
      cell stage.

PMID- 11302432
TI  - Cloning of a marsupial kappa-casein cDNA from the brushtail possum (Trichosurus
      vulpecula).
AB  - The main role of kappa-casein in milk is to stabilize the formation of casein
      micelles. Although marsupial milk contains casein micelles, kappa-casein had not
      been identified in any species. In these experiments, the first marsupial kappa
      casein has been prepared as enriched casein fractions and the cDNA cloned from
      the brushtail possum (Trichosurus vulpecula). Possum kappa-casein is a 158 amino
      acid peptide that shares low amino acid sequence identity (20-30%) with that of
      eutherian kappa-caseins. In the gut of suckling young, casein micelles clot when
      kappa-casein is cleaved by chymosin at a specific site. Eutherian kappa-casein
      sequences are classified according to the sequence of the chymosin cleavage site:
      Phe-Met, Phe-Ile or Phe-Leu. Possum kappa-casein appears to form a separate
      class, with a putative chymosin cleavage site of Phe-Ala, which is different from
      that found in eutherian mammals. Other features of kappa-caseins, such as the
      location of the N-terminal cysteine, solubility in the presence of calcium, and
      the O-glycosylation sites on threonine residues in the C-terminus of the
      molecule, are conserved in the possum sequence. The kappa-casein gene was
      expressed throughout lactation in the mammary gland, and although mRNA levels of
      kappa-, alpha- and beta-casein varied between animals there appeared to be a
      correlation in the expression of these genes within an individual animal. This
      suggests that a common transcription regulatory region may be controlling
      expression of all three genes in the possum.

PMID- 11302433
TI  - Freezability of boar spermatozoa is improved by exposure to 2-hydroxypropyl-beta
      cyclodextrin.
AB  - The influence of 2-hydroxypropyl-beta-cyclodextrin (HBCD) exposure on post-thaw
      spermatozoa prior to freezing using acrosome integrity and the parameters of
      motility was studied. Acrosomal status was monitored by means of FITC-labelled
      peanut agglutinin, and the motility parameters were assessed using a computer
      assisted sperm motility analysis (CASA) system. The spermatozoa were exposed to
      HBCD over a period of 3 h, during which the cells were slowly cooled from 25 to 5
      degrees C, and then frozen into pellets. The percentage of frozen thawed
      spermatozoa with intact acrosomes in 40 mM HBCD group was approximately three
      fold higher than that of the control. The motility and progressive motility
      values of the frozen-thawed spermatozoa were found to increase significantly with
      increased HBCD concentrations. On the other hand, further addition of cholesterol
      3-sulfate to the BF5 extender containing 20 mM HBCD resulted in a drastic
      decrease in the percentage of spermatozoa with intact acrosomes, and decreased
      motility and progressive motility, suggesting that cholesterol-sulfate probably
      counter-acted the protective action of HBCD. In conclusion, the results of the
      present study indicate that HBCD protected boar spermatozoa against freeze-thaw
      damage, possibly by means of stimulating the efflux of membrane cholesterol.

PMID- 11302434
TI  - Seasonal patterns of LH, testosterone and semen quality in the Northern pintail
      duck (Anas acuta).
AB  - This study characterized seasonal changes in circulating LH and testosterone and
      in semen production and quality in the Northern pintail duck. Plasma LH and
      testosterone were measured in blood samples collected weekly throughout the year
      from eight males exposed to natural fluctuations in day length and temperature.
      Semen quality was evaluated weekly in these same males from April-June, the
      months when spermatozoa were produced. Semen quality (based on sperm
      concentration and normal morphology) peaked 0-2 weeks after sperm production
      onset and decreased sharply before sperm production cessation in late June. Nadir
      LH concentrations were measured in July and August with peak LH observed in May
      and November. There were clear seasonal patterns in circulating testosterone with
      July-September values being less (P<0.05) than October-December which, in turn,
      were less (P<0.05) than January-March. Maximal circulating testosterone (P<0.05)
      occurred during April-June, coincident with semen production. Weekly circulating
      LH during the breeding season was directly related to testosterone concentrations
      (P<0.01), but was not correlated to any specific semen or sperm trait (P>0.05).
      Testosterone concentrations throughout the breeding season were correlated
      (P<0.05) to total numbers of spermatozoa produced (volume x cell concentration)
      and percent normal sperm morphology. In summary, the Northern pintail experiences
      seasonal hormone fluctuations, with maximum circulating testosterone coinciding
      with peak ejaculate quality reflected by the production of high numbers of
      morphologically normal spermatozoa.

PMID- 11302435
TI  - Structural changes of human serum albumin immobilized on chromatographic
      supports: a high-performance liquid chromatography and Fourier-transform infrared
      spectroscopy study.
AB  - Chiral stationary phases obtained by immobilization of HSA on [C8] and [C18]
      reversed-phases and on poly(1-vinylimidazole)-coated silica were tested to
      resolve DL-tryptophan, N-benzoyl-DL-phenylalanine, RS-oxazepam and RS-warfarin
      racemic mixtures. Parameters of enantioselectivity measured in HPLC are
      correlated to structural and solvation states for adsorbed HSA, evaluated by FTIR
      spectroscopy. HSA immobilized on [PVI]-anion-exchangers is highly selective. HSA
      molecules are not self-associated, only unfolded for a small hydrophobic helix.
      The HSA-coated reversed-phases have a lower selectivity. Unfolding is larger but
      the indole-benzodiazepine chiral site is preserved and remains accessible.

PMID- 11302436
TI  - Aggregation of amphiphilic pullulan derivatives evidenced by on-line flow field
      flow fractionation/multi-angle laser light scattering.
AB  - Size-exclusion chromatography (SEC) is a useful steric separation technique for
      the analysis of water-soluble polysaccharides in aqueous solution. However, in
      the case of amphiphilic derivatives, the usefulness is limited because of
      interactions between hydrophobic segments and the stationary phase. Alkyl-bearing
      pullulans differing from the extent and the length of alkyl groups were
      characterized using flow-field flow fractionation with on-line coupling multi
      angle laser light scattering (F4/MALLS). Comparison of SEC and F4 is presented
      and the interest of F4 in the field of amphiphilic derivatives is demonstrated.

PMID- 11302437
TI  - Kinetics study of the biotransformation of an oligonucleotide prodrug in cells
      extract by matrix-assisted laser desorption-ionization time-of-flight mass
      spectrometry.
AB  - The fate of a dodecathymidine prodrug in cell extract was monitored by MALDI-TOF
      MS. This technique allows a facile identification and a relative quantification
      of metabolites produced. We showed that the relative peak intensities were
      similar to the relative metabolite proportions that permitted the determination
      of their half-lives. We found a good fit between the calculated kinetics curves
      and the experimental points. The oligonucleotide prodrug was fully metabolized to
      yield the dodecathymidine phosphorothioate likely through a carboxyesterase
      mediated mechanism.

PMID- 11302438
TI  - Study of the retention properties of warfarin enantiomers on a beta-cyclodextrin
      polymeric support.
AB  - High-performance liquid chromatography was used to study the retention properties
      of (R)- and (S)-warfarins on a silica support coated with a beta-cyclodextrin
      polymer. The influence of the methanol content of the acetate buffer eluent was
      investigated at pH 4. The measure of the variations of retention time with
      temperature enables one to determine the enthalpy and the entropy of adsorption.
      The plot of the two thermodynamic functions shows a minimum around 30% (v/v)
      methanol. At low methanol contents, the decrease of the hydrophobic interactions
      with increasing methanol content explains the decrease of the enthalpic and
      entropic terms. Above 40% (v/v) methanol, the decrease of the adsorption enthalpy
      absolute value is due to the solvation by the organic component. From the
      analysis of peak shape in mass-overload conditions, the column capacity toward
      each enantiomer was determined. A lower capacity was found toward (S)-warfarin,
      the more retained enantiomer. Peak shape analysis in mass-overload conditions was
      used to determine the adsorption isotherm. A Langmuir-type adsorption isotherm
      accounts well for the experimental data.

PMID- 11302439
TI  - Fractionation of functional polystyrenes, poly(ethylene oxide)s and poly(styrene)
      b-poly(ethylene oxide) by liquid chromatography at the exclusion-adsorption
      transition point.
AB  - The paper reports the fractionation of functional polystyrenes (PSs) and
      poly(ethylene oxide)s (PEOs) as well as their block copolymers, by liquid
      chromatography at the exclusion adsorption transition point (EATP-LC), also
      called "critical conditions" mode. In this specific elution mode (EATP-LC), the
      fractionation is only governed by the nature and the number of functions attached
      to the polymer backbone, independent of the molar mass distribution of the whole
      sample. Functional polystyrenes (alpha- and/or alpha,omega-alcohol-, acetal-,
      aldehyde- and acidic-PS) could be readily separated from non-functional
      polystyrenes under various chromatographic conditions. The technique also allowed
      the fractionation of poly(ethylene oxide)s and PS-PEO block copolymers. In the
      latter cases, moderately polar columns (grafted silica) and water-based polar
      eluents were required to obtain a satisfactory fractionation.

PMID- 11302440
TI  - Quantification of gentamicin in Mueller-Hinton agar by high-performance liquid
      chromatography.
AB  - The aim of this study was to optimise a method for gentamicin determination in an
      agar matrix and to investigate if and how agar composition can affect the
      gentamicin diffusion kinetics during the agar diffusion tests for antibiotics
      sensitivity. Gentamicin was separated by RP-HPLC and detected at 365 nm after pre
      column derivatization with 1-fluoro-2,4-dinitrobenzene. Recovery (> or = 79%),
      linearity (r2 > or = 0.997) and sensitivity (1 microg/ml) were assessed using
      four different agar matrices. The kinetics of gentamicin diffusion tested on
      BioMerieux and DID manufacturers' products showed in uninoculated agar plates
      significant differences that were even more pronounced in the presence of
      Pseudomonas aeruginosa metabolism.

PMID- 11302441
TI  - Chromatographic study of highly methoxylated lime pectins deesterified by
      different pectin methyl-esterases.
AB  - The inter-molecular distribution of free carboxyl groups of two highly
      methoxylated pectins enzymatically deesterified by plant and fungus pectin methyl
      esterases were investigated by size-exclusion (SEC) and ion-exchange
      chromatography (IEC). "Homogeneous" populations with respect to molar mass or
      charge density were thereby obtained and their chemical composition and physico
      chemical properties (transport parameter for monovalent cations and calcium,
      calcium activity coefficient) were studied. Chemical analysis showed that the
      composition varies from one SEC fraction to another, the highest molar mass
      fraction being richer in rhamnose and galactose and exhibiting a slightly higher
      degree of methylation. Separation of pectins by IEC revealed a quite homogeneous
      charge density distribution for F58 contrary to P60 which exhibited a large
      distribution of methoxyl groups. The free carboxyl groups distributions and
      calcium binding behaviours of SEC and IEC fractions were shown to differ widely
      for highly methoxylated pectins deesterified by plant and fungus pectin methyl
      esterases.

PMID- 11302442
TI  - One-step chromatographic purification procedure of a His-tag recombinant carboxyl
      half part of the HTLV-I surface envelope glycoprotein overexpressed in
      Escherichia coli as a secreted form.
AB  - A His-tag recombinant carboxyl half part of the HTLV-I surface envelope
      glycoprotein was overexpressed in E. coli as a secreted form in order to study
      its biochemical properties and to determine its three-dimensional structure by X
      ray crystallography. Starting from several hundred milliliters of culture, a
      centrifugation was used to eliminate the cells. After solubilization and
      centrifugation, the protein was then purified by a one-step chromatographic
      purification procedure. Immobilized Metal Affinity Chromatography (IMAC) was
      performed by evaluating the tri-dentate iminodiacetic acid (IDA) chelating group
      with chelating Sepharose fast flow, and the tetra-dendate nitrilotriacetic acid
      (NTA) chelating group with NTA-agarose. The latter was the most suitable gel for
      our protein. This expression system and the use of affinity chromatography is a
      rapid technique to obtain a soluble protein for use in structural studies to
      further understand the mechanisms of HTLV-1 entry into target cells.

PMID- 11302443
TI  - The BPP (protein biochemistry and proteomics) two-dimensional electrophoresis
      database.
AB  - The BPP (protein biochemistry and proteomics) two-dimensional electrophoresis (2
      DE) database (http://www-smbh.univ
      paris13.fr/lbtp/Biochemistry/Biochimie/bque.htm) was established in 1998. The
      current release contains 11 reference maps from human hematopoietic and lymphoid
      cell line samples. These reference maps have now 255 identified spots,
      corresponding to 84 protein entries. The World Wide Web (WWW) presentation is
      designed to allow public access to the available 2-DE data together with logical
      connections to databases providing complementary information.

PMID- 11302444
TI  - Ultrafiltration to fractionate wheat polypeptides.
AB  - An ultrafiltration process allowing the fractionation of two kinds of
      polypeptides issued from limited chymotryptic hydrolysis of wheat gliadins was
      applied to wheat gluten hydrolysates. Hydrophilic and poorly charged polypeptides
      were well transmitted through an inorganic ZrO2-based membrane at acidic pH,
      whereas hydrophobic and positively charged polypeptides were highly retained. By
      combining reversed-phase and cation-exchange chromatography (CEC), it was proved
      that the fractionation of the polypeptides was based on electrostatic repulsion
      of the charged polypeptides by the positively charged membrane. After a
      continuous diafiltration process, retentates containing 75 to 88% of hydrophobic
      polypeptide and permeates containing 84 to 90% of hydrophilic polypeptides were
      recovered, depending on the size of membrane used. Even if the ultrafiltration
      fractions were less purified than fractions issued from CEC, it was shown that
      they exhibited very different foaming properties: permeate did not produce nor
      stabilize foams, whereas retentate was more efficient than the whole hydrolysates
      and BSA.

PMID- 11302445
TI  - Role of electrophoretic mobility of protein on its retention by an
      ultrafiltration membrane. Comparison to chromatography mechanisms.
AB  - Lysozyme and lactoferrin, two globular proteins, were first studied separately in
      order to elaborate a strategy for the improvement of their separation by
      ultrafiltration (UF) with zirconia-based membranes of different charge sign and
      pore radius. The electrophoretic mobility (mu) at fixed pH and variable ionic
      strength was used for the characterisation of both proteins and zirconia
      particles, similar to the active layer of the membrane during the UF run.
      Specific adsorption of phosphate ions was shown for both proteins resulting in
      new isoelectric points. The occurrence of electrostatic exclusion mechanism in
      addition to the molecular sieving in UF of charged solutes was shown for: * Low
      molecular weight solute: multivalent citrate at pH 6 was specifically adsorbed on
      zirconia and its transmission through the membrane (defined as the ratio of the
      concentration in the permeate to that of the feed solution) was reduced in the
      range 0.001-0.01 mol l(-1) of citrate concentration * Proteins: their
      transmissions increase when the ionic strength increases (ion-exchange is not the
      relevant mechanism because transmission is irrespective of the initial charge of
      the membrane compared with the protein charge). A model based on convection,
      diffusion and electrophoretic migration mechanisms (CDE model) was proposed to
      take into account this behaviour. The CDE model predicts the possible existence
      of a depleted sub-layer of the charged protein in the concentration polarisation
      layer, located in the close vicinity of the membrane surface. A strategy for the
      separation of two proteins in mixed solution was proposed by varying both the
      physico-chemical environment in the feed solution (pH, ionic strength, chemical
      nature of the electrolyte) and the membrane pore radius. Maximum selectivity was
      obtained when the target protein (to be transmitted in the permeate side) is
      close to being uncharged due to specific adsorption of electrolyte ions.
      Ultrafiltration selectivity is enhanced with membrane of large pore radius, which
      provides high transmission of the target protein and efficient electrostatic
      exclusion of the solute to be retained in the retentate side. This UF approach
      corresponds roughly to the separation of one uncharged and one charged protein
      from a mixed solution by size exclusion chromatography of the uncharged protein
      combined with electrostatic exclusion of the charged protein due to packing of
      similar charge.

PMID- 11302446
TI  - Reversed-phase high-performance liquid chromatography of peptides of porcine
      pepsin prepared by the use of various forms of immobilized alpha-chymotrypsin.
AB  - Reversed-phase high-performance liquid chromatography (RP-HPLC) separation was
      used for the comparison of peptide maps of pepsin after its digestions by
      different forms of immobilized alpha-chymotrypsin. Porcine pepsin was hydrolysed
      with soluble alpha-chymotrypsin, with alpha-chymotrypsins glycosylated with
      lactose or galactose coupled to hydrazide derivative of cellulose, with alpha
      chymotrypsin attached to poly(acrylamide-allyl glycoside) copolymer or to
      glycosylated hydroxyalkyl methacrylate copolymer Separon or to agarose gel
      Sepharose 4B. Efficiency of enzymatic protein cleavage with regard to peptide
      mapping of porcine pepsin has been examined by the use of alpha-chymotrypsins
      immobilized by different methods. Best results were achieved after hydrolysis
      with alpha-chymotrypsin immobilized on poly(acrylamide-allyl glycoside)
      copolymers. Alpha-chymotrypsin immobilized by this way has further three times
      higher relative specific activity in comparison with the soluble one. Modified
      alpha-chymotrypsin was not suitable for efficient pepsin cleavage.

PMID- 11302447
TI  - Efficient two-step chromatographic purification of penicillin acylase from
      clarified Escherichia coli ultrasonic homogenate.
AB  - A two-step chromatographic purification procedure from clarified Escherichia coli
      ultrasonic homogenate was evaluated. The capture step included immobilized metal
      affinity chromatography with Cu2+ as metal ion. Two elution methods were
      performed: 1 M NH4Cl and 0.01 M imidazole. Respectively, we obtained a different
      purification fold (16.5 to 3.15) and a similar result for the recovery of
      activity (90-99%). The best elution method was chosen for the procedure. The
      second step, hydrophobic interaction chromatography, gave a 3.8-fold purification
      with 77.7% of activity. The total procedure gave a 66-fold purification in
      relation to the initial crude extract with 70% for the recovery of activity and
      was performed without any conditioning step and at the same pH value.

PMID- 11302448
TI  - Purification of recombinant HBc antigen expressed in Escherichia coli and Pichia
      pastoris: comparison of size-exclusion chromatography and ultracentrifugation.
AB  - Hepatitis B virus core protein (HBc) is an important serology marker of hepatitis
      B infection and patient follow-up. It is an M, 21,000 protein, which has the
      intrinsic capacity to self-assemble as a capsid-like particle. The hepatitis B
      core protein has been expressed in Escherichia coli and Pichia pastoris (three
      different constructions) in order to select a HBc recombinant antigen suitable
      for serodiagnosis requirements with a cost effective downstream strategy. The
      expression and purification of the different forms of recombinant HBc have been
      described. For the last step, ultracentrifugation and size-exclusion
      chromatography were compared. The morphology of these capsids was observed using
      an electron microscope. Our data shows that HBc antigen is produced in large
      quantities in E. coli but some contaminants remained which were associated with
      the E. coli HBc protein after ultracentrifugation or size-exclusion
      chromatography. The ultracentrifugation enables a higher purity of HBc antigen to
      be obtained than size-exclusion chromatography but the latter enables a higher
      recovery rate. P. pastoris enables the expression and extraction of a highly
      purified HBc antigen suitable for diagnostic purposes.

PMID- 11302449
TI  - Specific adsorption of phosphate ions on proteins evidenced by capillary
      electrophoresis and reversed-phase high-performance liquid chromatography.
AB  - Specific adsorption of phosphate ions at pH=7.0 was studied on different
      proteins, either counter-ions of phosphate (lysozyme, lactoferrin) or co-ion of
      phosphate (alpha-lactalbumin). The theoretical electrophoretic mobility of
      globular proteins lysozyme and alpha-lactalbumin (apo and holo (+1 calcium per
      molecule) forms) was compared with those measured by capillary electrophoresis in
      phosphate at pH 7.0, versus the ionic strength (I) in the range 0-0.775 mol L(
      1). The specific adsorption of phosphate ions was evidenced by difference. From
      the experimental charge number (Z(eff)) of protein in phosphate medium, a
      phosphate content per protein molecule was determined at pH=7.0. * For
      lactoferrin (pI=8-9), the electrophoretic mobility (mu) was constant and
      negative, highlighting a charge reversal due to phosphate adsorption. * For alpha
      lactalbumin (holo form) experimental mu was roughly constant and more negative
      than predicted. Z(eff) increased continuously from -4 to -11 in the ionic
      strength range from 0.005 to 0.775 mol l(-1), respectively. Accordingly, one to
      six phosphates were bound per molecule, respectively. * For lysozyme,
      experimental electrophoretic mobility was positive but lower than predicted.
      Z(eff) was only discrete values +5 for I in the range 0.001-0.020 mol l(-1) and
      about +3 in the range 0.050-0.500 mol l(-1), whereas the theoretical Z value was
      +7 at pH = 7.0. Lysozyme bounds one phosphate at low ionic strength and about two
      three at higher ionic strength. Reversed-phase HPLC confirms that adsorption of
      phosphate is different for the three proteins.

PMID- 11302450
TI  - Binding of substituted phenol and aniline derivatives to the corn protein zein
      studied by high-performance liquid chromatography.
AB  - The interaction of 12 substituted phenol, three aminophenol and four substituted
      aniline derivatives with the corn protein zein was studied on zein-coated silica
      and alumina stationary phases by high-performance liquid chromatography using
      bidistilled water as mobile phase. Solutes were eluted from the zein-coated
      supports with different retention times indicating that they bind to the protein
      with different forces. They were more strongly retained on silica-based than on
      alumina-based support proving that the original adsorptive character of the
      support remains even after impregnation. The retention of solutes on both zein
      coated stationary phases significantly depended on the steric and electronic
      parameters of solutes and was independent of the calculated and measured
      lipophilicity parameters, indicating that hydrophobic forces are not included in
      the interaction of zein with these class of solutes. It has been concluded that
      the interaction is governed by steric and electrostatic forces.

PMID- 11302451
TI  - Effect of molecular parameters on the binding of phenoxyacetic acid derivatives
      to albumins.
AB  - The interaction of 12 phenoxyacetic acid derivatives with human and serum albumin
      as well as with egg albumin was studied by charge-transfer reversed-phase (RP)
      thin-layer chromatography (TLC) and the relative strength of interaction was
      calculated. Each phenoxyacetic acid derivative interacted with human and bovine
      serum albumins whereas no interaction was observed with egg albumin. Stepwise
      regression analysis proved that the lipophilicity of the derivatives exert a
      significant impact on their capacity to bind to serum albumins. This result
      supports the hypothesis that the binding of phenoxyacetic acid derivatives to
      albumins may involve hydrophobic forces occurring between the corresponding
      apolar substructures of these derivatives and the amino acid side chains.

PMID- 11302452
TI  - High-performance liquid chromatographic study of the interactions between
      immobilized beta-cyclodextrin polymers and hydrophobically end-capped
      polyethylene glycols.
AB  - The formation of inclusion complexes between polyethylene glycols (PEGs) bearing
      hydrophobic ends (naphtyl and phenyladamantyl) and beta-cyclodextrin polymers
      (poly beta-CD) immobilized onto silica particles was studied by high-performance
      liquid chromatography (HPLC). It was shown that hydrophobic interactions were
      involved in the retention mechanism of these compounds, since retention volumes
      decreased when organic solvents were added to the mobile phase while it was the
      contrary in the presence of salts. Moreover, the association could be reversed by
      adding a competitor (hydroxypropyl beta-cyclodextrin) to the mobile phase. A
      theoretical model permitted the evaluation of affinity constants of 1:1 complexes
      formed between the modified PEGs and the immobilized poly beta-CD which depended
      on the type of hydrophobic groups grafted to the PEG.

PMID- 11302453
TI  - Assessment of cognitive abilities in Hispanic children.
AB  - Equitable cognitive assessment of Hispanic children rests primarily on a thorough
      understanding of the manner in which test performance is affected by
      acculturation and language proficiency. Although current tests are
      psychometrically sophisticated, their use with Hispanic children is plagued by
      assumptions that have a discriminatory impact. Bias is a function of differences
      in experience between an individual and the norm group. By virtue of their
      emerging bilingualism and blended cultural backgrounds, Hispanic children are
      generally not represented adequately by any existing norm sample. By classifying
      tests according to degree of cultural loading and linguistic demand, a defensible
      and systematic approach to reducing bias in test selection and test
      interpretation can be achieved. Use of cultural and linguistic test
      classifications places a viable and practical method for reducing the
      discriminatory aspects of standardized tests in the assessment of Hispanic
      children within easy reach of most professionals.

PMID- 11302454
TI  - What test should I use?
AB  - Appropriate assessment of Hispanic children requires clinicians to have knowledge
      of the cultural and linguistic factors that influence the communication skills of
      these children. This knowledge base includes an understanding of variations in
      the social and linguistic characteristics of Hispanic subgroups. Knowledge of
      these characteristics provides clinicians with the framework necessary to conduct
      less biased assessments. Clinicians possessing this framework would be able to
      conduct assessments that take into consideration the child's social ecology and
      the impact of dialect, first and second language acquisition, and language loss
      on the child's communication skills.

PMID- 11302455
TI  - Assessing phonological skills in Hispanic/Latino children.
AB  - Phonological assessment of Hispanic/Latino children (many of whom are bilingual)
      is often difficult because of the limited information on appropriate assessment
      techniques. Without information on appropriate assessment strategies for these
      children, there may be a delay in their receiving diagnostic (and intervention)
      services and an inappropriate characterization of phonological skills in both
      typically developing children and children with phonological disorders. In order
      to assess the phonological skills of Hispanic/Latino children appropriately,
      speech-language pathologists (SLPs) must make modifications to the standard
      assessment protocol. To that end, SLPs must determine language of assessment,
      choose assessment tools, complete phonological analyses, and consider dialect in
      their assessment. The purpose of this article is to delineate the procedures for
      completing a thorough phonological assessment for Hispanic/Latino children.

PMID- 11302456
TI  - Assessment of semantic knowledge: use of feedback and clinical interviewing.
AB  - Assessment of semantic knowledge is particularly challenging for clinicians
      working with children from culturally and linguistically diverse backgrounds.
      Vocabulary often reflects individual experiences, home language, and familiarity
      with school curriculum. Research demonstrates that children from nonmainstream
      backgrounds often score poorly on vocabulary tests yet may possess knowledge that
      is not evident in the kinds of tests that they take. Thus, a single word
      vocabulary test may not adequately capture the scope of such children's semantic
      knowledge. It is important that, before a diagnosis of language impairment is
      made, clinicians gain insight into children's semantic knowledge. This article
      describes the use of two procedures, feedback and the clinical interview, that
      can be utilized to probe children's language abilities.

PMID- 11302457
TI  - Assessing morphosyntax in Spanish-speaking children.
AB  - Accurate assessment of the morpho-syntactic skills of Spanish-speaking children
      depends on the clinician's understanding of the morpho-syntactic system and on
      the development of tasks that obligate the use of structures of interest. In this
      article, the nature and acquisition of the Spanish morpho-syntactic system is
      outlined. The aspects of the system that are likely to be difficult for children
      with language impairments and those that are critical to communicative competence
      are emphasized, as the clinician must take these into account when planning
      assessment tasks. The analysis of spontaneous language samples and the use of
      structured probes are discussed as alternatives for assessment. The naturalness
      and linguistic demands of assessment tasks are also considered because they are
      critical to understanding children's performance on morpho-syntactic tasks.

PMID- 11302458
TI  - Examining the quality of children's stories: clinical applications.
AB  - Research has shown that narrative analysis is an appropriate method for assessing
      the narrative skills of children from diverse backgrounds. Child narrative
      studies are reviewed to show crosslinguistic similarities and differences across
      Spanish and English speakers. An approach that examines the quality of children's
      narratives based on research with Spanish-speaking children is then described.
      The protocol focuses on the plot, clarity, cohesion, specificity, and memorable
      features of narratives as assessment categories. Methodological issues are
      discussed, and narrative samples from two children with and without language
      impairment are used to illustrate the analysis.

PMID- 11302459
TI  - Epidemiology of autism in Singapore: findings of the first autism survey.
AB  - The report describes the results of a survey conducted on 176 parents of children
      with autism in Singapore. The ages of the children ranged from 3 to 12 years. The
      survey focused on the child's background, behaviour problems and skill profile,
      the home and school situation as well as the linguistic and social background. It
      was noted that the Singapore population confirms the international distribution
      regarding a predominance of boys over girls and a low incidence of birth
      complications. A positive trend noted was the fact that 60% of the children were
      diagnosed before the age of 3 years. Discussion focuses on possible risk factors
      and psychosocial adversities for autism such as a high frequency of caregivers
      who are foreign maids, the use of multiple languages and the high level of
      punitive educational practices. The possible influence of psychosocial
      deprivation on child development is discussed.

PMID- 11302460
TI  - Sensitivity of qualitative and quantitative spasticity measures to clinical
      treatment with cryotherapy.
AB  - This study examined the extent to which a battery of tests could detect a
      reduction of plantarflexor spasticity resulting from cryotherapy. The tests
      included a traditional qualitative spasticity scale, three potential quantitative
      spasticity measures and a measure of voluntary ankle muscle function. Twenty-six
      adult traumatic-brain-injured subjects were examined; these included 22 males and
      4 females. The mean age was 28.15 years (range: 18-57, SD 10.78). The five tests
      were performed in random sequence on both ankles of each subject, before and
      after a 20 minute cold pack application to the calf. Tests were: modified
      Ashworth scale (MAS) scoring; H-reflex testing with and without dorsiflexor
      contraction (Hdf/Hctrl ratio); H-reflex testing with and without Achilles tendon
      vibration (Hvib/Hctrl ratio); reflex threshold angle (RTA) and timed toe tapping
      (TIT). Cryotherapy resulted in lowered MAS scores consistent with a reduction in
      spasticity. Doubly multivariate repeated measures ANOVA revealed a significant
      difference (F = 24.16, P < 0.001) in test scores between the pre- and post
      cryotherapy test batteries. Significant pre- and post-cryotherapy differences (P
      < or = 0.03) for all dependent measures contributed to the main effect for
      cryotherapy. However, among the potential quantitative measures of spasticity
      only the RTA test demonstrated appropriate sensitivity to the reduction in
      spasticity. In spite of spasticity reduction, TIT performance was impaired
      following muscle cooling. Failure of the H-reflex ratios to show a reduction
      consistent with reduced spasticity was attributed to competing alpha and gamma
      motoneuron effects resulting from peripheral cooling.

PMID- 11302461
TI  - Integrative group therapy outcome related to psychosocial characteristics in
      patients with chronic pain.
AB  - Previous observations stress the importance of patient characteristics as
      contributors to treatment outcome. In this study the outcome of integrative pain
      group therapy was investigated in relation to prior treatment psychosocial
      characteristics in pain clinic outpatients with chronic pain. The patients
      participated in 10 weekly sessions (2 1/2 hours) of integrative pain group
      therapy consisting of cognitive-behavioural strategies and light physical
      exercises. After the 12-month follow-up the modified method of cluster analysis
      was applied on the admittance data of the sample of 47 patients in order to
      divide the subjects into three homogenized subgroups (Interpersonally Distressed
      patients, Adaptive Copers and Dysfunctional patients) with varying prior
      treatment characteristics. The outcome of treatment was analysed by comparing the
      effect of intervention on the psychosocial functional profiles of the subgroups.
      The functional profiles were assessed by a six-scale self-report questionnaire
      describing the psychosocial components of three functional dimensions as
      recommended by the World Health Organization (1999). The results supported the
      previous conclusions that prior treatment functional profiles are important
      contributors to pain treatment outcome. However, the results also suggested that
      cluster analysis technique may be a very robust method to divide patients into
      'homogenized' subgroups.

PMID- 11302462
TI  - Head injury and family carers: a critical appraisal of case management programmes
      in the community.
AB  - The objective of this review was to identify the available support systems for
      family carers of head-injured people within the community. The following
      databases were searched: MEDLINE, EMBASE PSYCHIATRY, CINAHL and PSYCHLIT (years
      1987-1999). Only seven papers were identified. Programmes varied from behavioural
      to cognitive interventions to help carers adjust to particular problem behaviours
      in their injured relatives. All programmes were professionally led. Most of the
      data presented was on primary caregivers related to the head-injured person. Only
      one study used standard assessment tools. The remainder used a variety of methods
      including self-report measures and interviews. All interventions were reported as
      beneficial to carers. Overall these studies were found to be limited by biased
      sampling, nonstandardized outcome measures using subjective methodologies and a
      lack of control samples. Most studies did not reveal pertinent information
      regarding the degree and type of head injury or rehabilitation history. There is
      an outstanding requirement for large randomized controlled studies using
      standardized methodologies to identify efficacious carer programmes.

PMID- 11302463
TI  - Aspects of the quality of life of chronically ill and handicapped children and
      adolescents in outpatient and inpatient rehabilitation.
AB  - The aim of psychosocial rehabilitation is to reduce handicaps as far as possible.
      One handicap in chronically ill adolescents is the impairment of quality of life.
      The quality of life of chronically ill or handicapped adolescents can be defined
      with a bio-psycho-social model. The connections between adaptivity level,
      severity of the physical disability and experienced helplessness of young
      wheelchair users with paraplegia or tetraplegia are demonstrated. Advantages of
      inpatient and outpatient rehabilitation with regard to quality of life are
      reported.

PMID- 11302464
TI  - Effects of alternated sport competition in perceived competence for adolescent
      males with mild to moderate mental retardation.
AB  - Since the beginning of the 1990s, two types of organized competitive sport
      (Segregated or Integrated) have been proposed for adolescents with mental
      retardation (AMR). These programmes often have as an objective the improvement of
      the individual's perceived competence. In France, a third competitive system,
      called Alternated sport meets (Segregated and Integrated) is actually used. The
      purpose of this study is to examine the effects of this type of programme and
      type of sport (basketball versus running) on domains of perceived competence and
      general self-worth. The participants were 32 AMR (Mean age 13.5 years, SD = 0.80)
      divided equally into four groups: (a) alternated basketball; (b) alternated
      running; (c) control, adapted physical activity; (d) control, sedentary. The
      experimental treatment was for 7 months. The sport groups participated in 2 hours
      training each week and six competitive meets. We administrated Harter's (1985)
      Self-Perception Profile for Children seven times to determine changes in
      perceived competence and general self-worth. Results indicated no significant
      changes in the specific domains of perceived competence and general self-worth.

PMID- 11302465
TI  - Usefulness of the Functional Independence Measure (FIM), its subscales and
      individual items as outcome measures in Guillain Barre syndrome.

PMID- 11302466
TI  - Functional independence measure versus short form-36: relative responsiveness and
      validity.

PMID- 11302467
TI  - Disability status, perceived health, social support, self-efficacy, and quality
      of life among people with spinal cord injury in the People's Republic of China.

PMID- 11302468
TI  - Work adjustments among the chronically ill.
AB  - Work(place) adjustments can help restore the work capacity of persons with a
      chronic disease. This study aims to quantify the presence of work adjustments
      among chronically ill workers in the Netherlands, and to investigate the extent
      to which the presence of work adjustments are related to the experience of work
      interfering problems, disease characteristics or work characteristics. Data for
      this study are derived from the Dutch Panel of Patients with Chronic Diseases.
      The results discussed here relate to data collected in 1999 from a representative
      sample of 556 working people with various chronic somatic diseases. Of the work
      interfering problems, the ones related to physical disabilities, concentration or
      memory deficits and transportation emerged as the most important factors related
      to the presence of either immaterial (i.e. not material) or material work
      adjustments. In addition, higher age and lower educational level were associated
      with a higher probability of immaterial adjustments; pain, attack frequency and
      physical demands of the job were important predictors of material work
      adjustments.

PMID- 11302469
TI  - Length of hospital stay, functional independence and life satisfaction after
      stroke.

PMID- 11302470
TI  - Korean students' differential attitudes toward people with disabilities: an
      acculturation perspective.

PMID- 11302471
TI  - Factor XIIIA and clot strength after cardiopulmonary bypass.
AB  - Reduced factor XIIIA levels and decreased clot strength have been associated with
      increased bleeding after cardiopulmonary bypass (CPB). The purpose of this study
      was to evaluate the relationship between hemostatic factors, including factor
      XIIIA, and clot strength before, during and after CPB. Factor XIIIA antigen,
      platelet counts, fibrinogen, factor V activity, tissue plasminogen activator and
      clot strength (by thromboelastograph) were measured at baseline, after 45 min of
      CPB, at the end of CPB and 4 h post-operatively in 34 patients. Baseline factor
      XIIIA antigen was 5.2 +/- 1.4 mg/l. On average, factor XIIIA levels dropped to
      64% and clot strength to 77% of baseline values after 45 min on CPB and remained
      below baseline during the immediate post-operative period. Clot strength was
      significantly correlated (r = 0.81) with platelet count and fibrinogen but not
      plasma factor XIIIA levels. Addition of 10 mg/l recombinant factor XIII[a2]
      significantly increased clot strength. Postoperative bleeding at 2 h was
      inversely correlated with platelet count, factor XIIIA antigen and clot strength
      measured at the end of CPB. Maintenance of adequate platelet counts and factor
      XIIIA levels at the end of CPB may play a role in maintaining clot strength and
      reducing blood loss.

PMID- 11302472
TI  - Acute hyperglycemia increases soluble P-selectin in male patients with mild
      diabetes mellitus.
AB  - The aim of this study was to examine if acute hyperglycemia (an oral glucose
      tolerance test) activates platelet function, endothelial cells or thrombin
      generation in diabetic patients and healthy controls. Eleven males with mild type
      II diabetes mellitus and 11 healthy male volunteers, matched for age and body
      mass index, were investigated before and after the glucose load. Soluble P
      selectin, von Willebrand factor antigen and markers of thrombin generation in
      plasma were determined by immunoassays, and platelet P-selectin expression
      (unstimulated and agonist-stimulated) by flow cytometry in whole blood. Acute
      hyperglycemia elevated plasma soluble P-selectin from 32.5 to 50.9 ng/ml in the
      diabetic group (P = 0.05) but not in the controls (from 27.3 to 28.8 ng/ml; P =
      0.6). Also, soluble P-selectin levels were higher in patients with diabetes than
      in healthy controls during hyperglycemia, but not in the fasting state. Adenosine
      diphosphate- and thrombin-induced platelet P-selectin expression was slightly,
      but significantly, decreased by the glucose load, whereas platelet P-selectin
      expression in unstimulated samples was not affected. Plasma levels of von
      Willebrand factor and thrombin generation were similar in patients and controls,
      and were not altered by hyperglycemia. In conclusion, we found that acute
      hyperglycemia elevates soluble P-selectin in plasma in males with mild type II
      diabetes mellitus. Our observation of unaltered plasma levels of the endothelial
      marker von Willebrand factor is in agreement with platelets being the main source
      of P-selectin released into plasma following hyperglycemia. Thus, platelets in
      individuals with type II diabetes may be more susceptible to hyperglycemia than
      platelets in non-diabetic individuals.

PMID- 11302473
TI  - A high-fat meal does not activate blood coagulation factor VII in minipigs.
AB  - It is a matter of debate whether postprandial activation of blood coagulation
      factor VII (FVII) is associated with an increased risk of thrombosis. To clarify
      this question, an animal model in which consequences of dietary FVII activation
      can be studied in a more detailed way would be an important tool. We studied
      postprandial FVII activation in seven non-fasting Gottingen minipigs. Intralipid
      (4 g/kg) was administered through a gastric tube in two fractions at 9.00 a.m.
      (one-third of total dose) and 10.30 a.m. (two-thirds of total dose). Blood
      samples were drawn 0.5 h before (baseline) and 2, 3, 3.5, 4, 5, and 6 h after the
      first fat load. Triglycerides, activated FVII (FVIIa), FVII coagulant activity
      (FVIIc), FVII amidolytic activity (FVIIam) and prothrombin fragment I + 2 (F1 +
      2) were analysed in plasma samples. Median plasma triglycerides were
      significantly raised from 0.67 mmol/l (baseline) to 2.56 mmol/l 5 h
      postprandially (P < 0.001). There were no significant changes in FVIIa (9.6 U/l
      at baseline), FVIIam (142% at baseline) and F1 + 2 (0.13 nmol/l at baseline).
      FVIIc decreased from 141% at baseline to 114% 6 h postprandially (P < 0.001). As
      a high-fat meal does not seem to activate blood coagulation FVII in minipigs, the
      pig is apparently not a relevant model for the study of dietary FVII activation
      and thrombin generation.

PMID- 11302474
TI  - Screening for selective thrombin inhibitors in mushrooms.
AB  - Thrombin is the key serine proteinase of the coagulation cascade and therefore a
      suitable target for inhibition of blood coagulation. A number of
      pharmacologically active secondary metabolites from mushrooms have already been
      isolated, thus providing the rationale for screening for new thrombin inhibitors
      in mushrooms. In this study, inhibitory activities of mushroom extracts on
      thrombin and trypsin were measured using the chromogenic substrates H-D
      phenylalanine-L-pipecolyl-L-arginine-paranitroaniline dihydrochloride (S-2238)
      for thrombin and N-benzoyl-D,L-Arg-p-nitroanilide (BAPNA) for trypsin. The
      inhibitory activities of extracts from 95 Basidiomycete species have been
      determined. The majority of samples inhibited trypsin and thrombin with various
      potencies; however, some extracts showed no activity against one or both of the
      enzymes. An aqueous extract of Gleophyllum odoratum exhibited high inhibitory
      activity on both thrombin and trypsin (72 and 60%, respectively), while extracts
      of Clitocybe gibba, Amanita virosa, Cantharellus lutescens, Suillus tridentinus,
      Hypoloma fasciculare and Lactarius badiosanguineus considerably inhibited
      thrombin (49, 48, 36, 34, 32 and 31%, respectively) and showed no inhibitory
      activity on trypsin. The results at this point are promising for further research
      with the objective of finding an effective and safe thrombin inhibitor.

PMID- 11302476
TI  - A direct, automated, immuno-turbidimetric assay of free protein S antigen in
      plasma.
AB  - A new, fully automated, one-step, immuno-turbidimetric assay of free protein S
      (fPS) in plasma (STA Liatest Free Protein S; Diagnostica Stago, Asnieres, France)
      has been developed for STA analysers. This technique combines the advantages of a
      direct assay of fPS using two monoclonal antibodies, which specifically recognize
      fPS but not protein S (PS)-C4b-binding protein complexes, and the advantages of
      automation. The assay has good analytical performances, with intra- and inter
      assay variation coefficients below 5% for normal values, and slightly higher for
      abnormal values. In a comparison study with a one-step enzyme-linked
      immunosorbent assay for fPS (Asserachrom Free Protein S; Diagnostica Stago), a
      correlation coefficient of 0.93 with a regression line close to 1 was found
      between the two techniques (n = 166 normal or PS-deficient plasma samples
      collected from healthy subjects and individuals with a personal or family history
      of thrombosis). This new technique is specific, reproducible, easy to perform,
      and provides a useful tool in the diagnosis of PS deficiency.

PMID- 11302475
TI  - Epsilon-aminocaproic acid promotes the release of alpha2-antiplasmin during and
      after cardiopulmonary bypass.
AB  - This double-blind, randomized study compared the mechanisms by which low-dose
      aprotinin and epsilon-aminocaproic acid (EACA) inhibited fibrinolysis during
      cardiopulmonary bypass surgery. D-dimer levels during and after bypass were
      similar, indicating an equivalent inhibition of fibrinolysis. Effects on tissue
      plasminogen activator release were not associated with the inhibition of
      fibrinolysis by either drug. Treatment with EACA was associated with a
      substantial release of endogenous alpha2-antiplasmin, particularly 1 h after
      bypass. Compared with the aprotinin group, higher levels of the plasmin-alpha2
      antiplasmin complex in the EACA group confirmed an increased inhibition of
      plasmin by alpha2-antiplasmin. In conclusion, it is hypothesized that EACA
      inhibited fibrinolysis by stimulating the release of the patients' own alpha2
      antiplasmin.

PMID- 11302477
TI  - The management of von Willebrand's disease-associated gastrointestinal
      angiodysplasia.
AB  - There is a recognized association between von Willebrand's disease and
      gastrointestinal angiodysplasia. Most previous publications have been reports of
      the association itself and there is little published on the management and long
      term follow-up of affected patients. We report our experience and follow-up of
      six patients, and review the previous literature.

PMID- 11302478
TI  - Accumulation of low molecular mass heparin during prophylactic treatment in
      pregnancy.
AB  - A history of thromboembolism is associated with an increased risk of new
      thromboembolic events during pregnancy. Prophylaxis with heparin during pregnancy
      implicates long-term treatment with daily injections with either unfractionated
      heparin (UFH) or low molecular mass heparin (LMMH). Prolonged treatment with
      heparin may result in endothelial absorption and drug accumulation. In order to
      test this hypothesis, anti-FXa activity during pregnancy was measured in four
      women allergic to conventional UFH, who were treated with LMMH (dalteparin;
      Pharmacia). It was found that, at the commencement of treatment, it took more
      than 8 days to reach a steady maximum peak value, located 3 h after the given
      dose. One daily dosage of 5,000 IU anti-Xa resulted in a measurable level of FXa
      for 24 h in pregnancy week 40, compared with 17h at pregnancy week 37. The
      implications of an elevated anti-FXa activity during pregnancy, especially during
      the third trimester and at partus, are discussed. We present a reduced dose
      regime near term and during delivery.

PMID- 11302479
TI  - Management of heparin allergy during pregnancy with danaparoid.
AB  - We report a patient who presented with a left proximal deep vein thrombosis at 25
      + 5 weeks gestation. She developed a severe urticarial rash 3 weeks following
      initiation of therapy with Enoxaparin. The patient was heterozygous for the
      factor V Leiden mutation. She was treated with subcutaneous twice-daily
      danaparoid (Orgaran) for the remainder of the pregnancy, achieving anti-Xa levels
      in the therapeutic range 0.5-1.0 IU/ml. Delivery was at term by caesarean section
      2 days after spontaneous rupture of membranes and failure to progress in labour.
      Danaparoid was withheld during this time. Danaparoid was restarted 3 h post
      delivery and the patient anticoagulated with warfarin in the post-partum period.
      There was no recurrence of thrombosis or bleeding events during therapy with
      danaparoid. No anti-Xa activity was demonstrated in breast milk.

PMID- 11302480
TI  - Heterozygous carrier of G20210A prothrombin mutation used oral contraceptive
      treatment for 23 years without thrombotic events, and developed cerebral venous
      thrombosis 1 month after resumption of the medication at the age of 50.

PMID- 11302481
TI  - International Society on Antiphospholipid Antibodies, Tours, France, 12-16
      September 2000.

PMID- 11302483
TI  - Frequency of natural coagulation inhibitor (antithrombin III, protein C and
      protein S) deficiencies in Japanese patients with spontaneous deep vein
      thrombosis.
AB  - One hundred and thirteen consecutive Japanese patients with deep venous
      thrombosis (DVT) were studied for the incidences of antithrombin III (AT-III),
      protein C (PC) and protein S (PS) deficiencies, and the results were compared
      with those of normal subjects. Ten of the 392 normal Japanese subjects were found
      with PS deficiency (n = 8, 2.02%) or PC deficiency (n = 2, 0.5%). PS deficiencies
      comprised type I (1/8, 12.5%), type 11 (4/8, 50%), and type III (3/8, 37.5%). All
      PC deficiencies were type I. Among patients with DVT, 32 (28.3%) were deficient
      in AT-III, PC and PS. These patients consisted of two AT-III deficiency (1.77%),
      nine PC deficiency (7.96%), 20 PS deficiency (17.7%), and one combined deficiency
      of PC and PS (0.88%). Both of the patients with AT-III deficiency were classified
      as type II, all those with PC deficiency as type I, and those with PS deficiency
      as type I in 25% (5/20), type II in 55% (11/20) and type III in 20% (4/20). The
      frequency of PC and PS deficiencies in patients with DVT were 15.6 and 7.38 times
      the control population frequency, respectively, and this difference was
      statistically significant (P < 0.05). These data suggest that the Japanese
      population has a high frequency of PC and PS deficiencies. We recommend that PS
      activity should be measured for screening of thrombosis since type II deficiency
      accounted for approximately 50% of PS deficiency cases in both patients and the
      normal group in the Japanese.

PMID- 11302482
TI  - Reversible shear-mediated platelet dysfunction during cardiac surgery as assessed
      by the PFA-100 platelet function analyzer.
AB  - We undertook this investigation to assess alterations in shear-mediated platelet
      function during cardiac surgery and to determine the potential for the PFA-100 to
      predict post-operative bleeding. Platelet aggregation and PFA-100 closure times
      were determined in 18 adult patients at five intervals during cardiac surgery.
      Associations between post-operative bleeding and closure times were examined in
      an additional 58 patients. Statistical analysis consisted of Student's t,
      Wilcoxon signed rank, and Spearman correlation tests. All results are reported as
      mean +/- SEM. Collagen/epinephrine closure times were prolonged prior to and
      throughout surgery. Collagen/adenosine-5'-diphosphate (ADP) closure times were
      significantly prolonged by heparin administration, 141 +/- 15 s versus 115 +/- 10
      s (P = 0.01), and subsequent initiation of cardiopulmonary bypass (CPB), 203 +/-
      12 s (P= 0.0001); however, 15 min after protamine administration, closure times
      returned to near pre-operative values, 138 +/- 12 s (P = not significant). In
      contrast, platelet aggregation in response to ADP remained impaired in 17 of 19
      patients after CPB. Neither ex vivo correction of sample hematocrits nor
      supplementation with Humate P affected closure times. Positive and negative
      predictive values for post-CPB collagen/ADP closure times to predict bleeding
      were 18 and 96%, respectively. These results suggest that factors both intrinsic
      and extrinsic to the platelet contribute to reversible shear-mediated platelet
      dysfunction during CPB, and that the PFA-100 may prove useful after CPB to
      identify patients unlikely to benefit from platelet transfusions.

PMID- 11302484
TI  - A family of depsi-peptide fungal metabolites, as selective and competitive human
      tachykinin receptor (NK2) antagonists: fermentation, isolation, physico-chemical
      properties, and biological activity.
AB  - Four tachykinin (NK2) receptor inhibitors, SCH 378161 (1), SCH 217048 (2), SCH
      378199 (3), and SCH 378167 (4) were isolated from the fermentation broth of a
      taxonomically unidentified fungus. These compounds were separated from the
      fermentation broth by ethyl acetate extraction. Purification and separation of
      the individual compounds were achieved by NK2 assay-guided fractionation using
      gel filtration, reverse phase chromatography and HPLC. They were identified to be
      a family of depsipeptides by spectroscopic and degradation studies. Compounds 1
      and 3 contain proline and differ as an amide and acid whereas 2 and 4 contain
      pipecolic acid and differ in being an amide and acid. All of these compounds
      contain an identical hydroxy acid. They are selective NK2 inhibitors with Ki
      values ranging from 27-982 nM and demonstrate no activity at 10 microM in the NK1
      and NK3 assays. In addition, compounds 1 and 2 inhibited NKA-induced increases in
      the concentration of intracellular Ca2+, [Ca2+]i, in a CHO cell expressing the
      human NK2 receptor; this inhibition was competitive in nature with pA2 values of
      7.2 and 7.5, respectively. These data demonstrate that these natural products are
      selective and competitive receptor antagonists of the human NK2 receptor.

PMID- 11302485
TI  - FR198248, a new anti-influenza agent isolated from Apsergillus terreus No 13830.
      I. Taxomony, fermentation, isolation, physico-chemical properties and biological
      activities.
AB  - A novel anti-influenza agent, FR198248, was isolated from the cultured broth of a
      fungal strain No.13830. The strain was identified as Aspergillus terreus from
      morphological characteristics. FR198248, a new type of hydroxyl benzaldehyde
      compound, showed antiinfluenza virus activity in Madin-Darby canine kidney (MDCK)
      cells in vitro. The mode of action of FR198248 against influenza virus A could be
      ascribed to an inhibitory effect on the stage of virus adsorption. Furthermore,
      FR198248 possessed potent in vivo anti-influenza activity in a murine model of
      respiratory tract infection.

PMID- 11302486
TI  - Studies on the biosynthesis of epothilones: the PKS and Epothilone C/D
      monooxygenase.
AB  - Nonproducer mutants support the assumption that epothilones A and B are
      synthesized by the same polyketide synthase (PKS). The endproducts of the PKS,
      epothilones C and D, compete for the active site of a constitutively synthesized
      monooxygenase which is regulated by product inhibition. The postulated C-13
      hydroxy-epothilones as direct precursors of epothilones C and D were not
      detected.

PMID- 11302487
TI  - Haliangicin, a novel antifungal metabolite produced by a marine myxobacterium. 1.
      Fermentation and biological characteristics.
AB  - Haliangicin, a novel beta-methoxyacrylate antibiotic with a conjugated tetraene
      moiety, was isolated from the culture broth of a marine myxobacterium. A
      bacterium tentatively named as Haliangium luteum required 2-3% NaCl for the
      growth and production of haliangicin. Haliangicin inhibits the growth of a wide
      spectrum of fungi but was inactive against bacteria. In mitochondrial respiratory
      chains, haliangicin interfered the electron flow within the cytochrome b-c1
      segment.

PMID- 11302488
TI  - Haliangicin, a novel antifungal metabolite produced by a marine myxobacterium. 2.
      Isolation and structural elucidation.
AB  - A novel antifungal antibiotic, haliangicin, was isolated from a culture broth of
      marine myxobacterium, Haliangium luteum. The planar structure of haliangicin was
      elucidated by spectroscopic analyses and was shown to be a new polyunsaturated
      compound containing beta-methoxyacrylate moiety.

PMID- 11302489
TI  - Glycosylative inactivation of chalcomycin and tylosin by a clinically isolated
      Nocardia asteroides strain.
AB  - Studies on the susceptibility of pathogenic Nocardia to macrolide antibiotics,
      chalcomycin and tylosin, showed that most of the Nocardia species examined were
      highly resistant to both antibiotics, although N. nova was moderately
      susceptible. N. asteroides IFM 0339 converted these macrolides into inactive
      metabolites by glycosylation at 2'-OH or glycosylation and reduction of the 20
      formyl group. The structures of the metabolites were determined from NMR and MS
      data to be 2'-[O-(beta-D-glucopyranosyl)]chalcomycin (2), 2'-[O-(beta-D
      glucopyranosyl)]tylosin (5) and 20-dihydro-2'-[O-(beta-D-glucopyranosyl)]tylosin
      (4).

PMID- 11302490
TI  - Differentiating the biosynthesis of pseudomonic acids A and B.
AB  - Pseudomonic acid A (1) has been the dominant commercial pseudomonate antibiotic
      produced by Pseudomonas fluorescens. In specific shaken flask conditions initial
      fermentation accumulation of 1 is followed by preferential accumulation of the 8
      hydroxy derivative, pseudomonic acid B (2). Biosynthetic probing with a pulse of
      [1-14C] acetate or L-[methyl-14C] methionine at early, mid and late stages of the
      fermentation gave relative patterns of radioactivity in 1 and 2 that are
      inconsistent with an assumption that 2 arises by oxidation of 1, or that 1 is
      formed by reduction of 2. Since [methyl-14C] methionine only labels carbons in
      the 12-carbon part of the pseudomonate molecule that is thought to be an early
      biosynthetic moiety, the evidence from radiolabelling experiments implies that
      preferential early oxidation of this biosynthetic intermediate causes the pathway
      diversion to accumulate 2 instead of 1.

PMID- 11302491
TI  - Ampullosporines B,C,D,E1,E2,E3 and E4 from Sepedonium ampullosporum HKI-0053:
      structures and biological activities.

PMID- 11302492
TI  - Cyclo(D-Pro-L-Val), a specific beta-glucosidase inhibitor produced by Aspergillus
      sp. F70609.

PMID- 11302493
TI  - UCF76 compounds, new inhibitors of farnesyltransferase produced by Streptomyces.

PMID- 11302494
TI  - Phoenistatin, a new gene expression-enhancing substance produced by Acremonium
      fusigerum.

PMID- 11302495
TI  - Synthesis of a new polycyclic quinone by reduction of a dihydrobenz.

PMID- 11302496
TI  - Site-specific structural transformation of the novel antifungal cyclic
      depsipeptide FR901469: synthesis and biological activity of FR203903.

PMID- 11302497
TI  - Evaluation of the growth and inhibition strength of hydrocarbon solvents against
      Escherichia coli and Pseudomonas putida grown in a two-liquid phase culture
      system consisting of a medium and organic solvent.
AB  - The growth of microorganisms is often inhibited in a two-liquid phase culture
      system consisting of an aqueous medium and a large volume of hydrophobic solvent.
      Escherichia coli and Pseudomonas putida were cultured in a two-phase system
      containing a solvent with a log Pow value in a range of 2.1 to 6.0. The increase
      in the cell mass was monitored by increase in turbidity of the medium phase. We
      devised a semiquantitative method to evaluate the growth inhibition strength of
      solvents based on the relative amount of bacterial growth occurring in the two
      phase system. Analyses of growth of the bacteria by this method showed that the
      growth inhibition strength of a given solvent was usually but not always
      correlated inversely with its polarity. It is clear that growth inhibition
      strength is not determined simply by polarity of the solvent.

PMID- 11302498
TI  - Selection of stabilized 3-isopropylmalate dehydrogenase of Saccharomyces
      cerevisiae using the host-vector system of an extreme thermophile, Thermus
      thermophilus.
AB  - A leuB strain of Thermus thermophilus TTY1, was transformed with a plasmid vector
      that directed expression of 3-isopropylmalate dehydrogenase (IPMDH) of
      Saccharomyces cerevisiae encoded by the LEU2 gene. The original strain could not
      grow at 50 degrees C without leucine, probably because of the low stability of S.
      cerevisiae IPMDH. The mutants that could grow without leucine were selected at 50
      degrees, 60 degrees, 62 degrees, 65 degrees, 67 degrees, and 70 degrees C, step
      by step. All the mutant strains except for one isolated at 50 degrees C
      accumulated mutations. Mutations were serially accumulated: Glu255Val, Asn43Tyr,
      Ala62Thr, Asn110Lys, and Alal 12Val, respectively, at each step. The analyses of
      residual activity after heat treatment and the denaturation profile as monitored
      by circular dichroism showed that thermal stability was increased with
      accumulation of the mutations. The kinetic parameters of most mutant enzymes were
      similar to those of the wild type. However, some mutant enzymes showed a reverse
      correlation between stability and activity: the enzymes with a large increase in
      thermal stability showed lower activity. Although the wild-type enzyme is
      unstable in the absence of glycerol, the stabilizing effect of glycerol was not
      observed for all the mutant enzymes containing the Glu255Val substitution, which
      is assumed to be located at the hydrophobic interface between two subunits.

PMID- 11302499
TI  - 16S rDNA diversity of cultured and uncultured prokaryotes of a mat sample from
      Lake Fryxell, McMurdo Dry Valleys, Antarctica.
AB  - The prokaryotic diversity of aerobic and anaerobic bacterial isolates and of
      bacterial and archaeal 16S rDNA clones was determined for a microbial mat sample
      from the moated region of Lake Fryxell, McMurdo Dry Valleys, Antarctica. Among
      the anaerobic bacteria, members of Clostridium estertheticum and some other
      psychrotolerant strains dominated whereas methanogens and other Archaea were
      lacking. Isolates highly related to Flavobacterium hibernum, Janthiniobacterium
      lividum, and Arthrobacter flavus were among the aerobic bacteria most frequently
      isolated. Assessment of more than 350 partial 16S rDNA clone sequences of
      libraries generated by Bacteria- and Archaea-specific PCR primers revealed a rich
      spectrum of bacterial diversity but only two different archaeal clone sequences.
      Among the Bacteria, representative sequences belonged to the class
      Proteobacteria, order Verrucomicrobiales, class Actinobacteria,
      Clostridium/Bacillus subphylum of Gram-positives, and the Cytophaga
      Flavobacterium-Bacteroides phylum. The clones formed about 70 higher taxonomy
      groups (<98% sequence similarity) and 133 potential species, i.e., groups of
      clones sharing greater than 98% similarity. Only rarely were clone sequences
      found to be highly related to Lake Fryxell isolates and to strains of described
      species. Subsequent analysis of ten sequencing batches of 36 individual clones
      indicated that the diversity might be still higher than had been assessed.

PMID- 11302500
TI  - Probing stability-activity relationships in the thermophilic proteasome from
      Thermoplasma acidophilum by random mutagenesis.
AB  - Structural perturbations (L65H, V12L/M27T, F35V) generated by random mutation of
      the beta-subunit were used to probe the relationship between stability and
      activity in the thermophilic proteasome from Thermoplasma acidophilum. The
      optimum temperature for activity of each mutant (approximately 95 degrees C)
      remained unchanged; however, each mutant was significantly less stable than the
      wild type. Stability, therefore, is not the factor limiting high-temperature
      activity. Interestingly, mutation L65H drastically reduced stability without
      affecting specific activity over a wide temperature range, providing evidence
      that activity and stability can be decoupled. To investigate the nature of the
      flexibility introduced by mutation, stability of the proteasome was examined
      under pressure. The application of 10,000 psi stabilized the wild-type proteasome
      3.4 fold at 97 degrees C. When inactivation temperatures were chosen such that
      the rate of inactivation of the mutants was similar to that of the wild type,
      mutants with changes at the intersubunit interfaces (L65H and V12L/M27T) were
      similarly stabilized. Pressure was less effective in stabilizing mutant F35V,
      however, in which the substitution may have introduced a new pathway for
      inactivation.

PMID- 11302501
TI  - Cloning of two pectate lyase genes from the marine Antarctic bacterium
      Pseudoalteromonas haloplanktis strain ANT/505 and characterization of the
      enzymes.
AB  - A marine Antarctic psychrotolerant bacterium (strain ANT/505), isolated from sea
      ice-covered surface water from the Southern Ocean, showed pectinolytic activity
      on citrus pectin agar. The sequencing of the 16S rRNA of isolate ANT/505
      indicates a taxonomic affiliation to Pseudoalteromonas haloplanktis. The
      supernatant of this strain showed three different pectinolytic activities after
      growth on citrus pectin. By activity screening of a genomic DNA library of
      isolate ANT/505 in Escherichia coli, two different pectinolytic clones could be
      isolated. Subcloning and sequencing revealed two open reading frames (ORF) of
      1,671 and 1,968 nt, corresponding to proteins of 68 and 75 kDa, respectively. The
      deduced amino acid sequence of the two ORFs showed homology to pectate lyases
      from Erwinia chrysanthemi and Aspergillus nidulans. The pectate lyases contain
      signal peptides of 17 and 26 amino acids that were correctly processed after
      overexpression in E. coli BL21. Both enzymes were purified by anionic exchange
      chromatography. Maximal enzymatic activities for both pectate lyases were
      observed at 30 degrees C and a pH range of 9 to 10. The Km values of both lyases
      for pectate and citrus pectin were 1 g l(-1) and 5 g l(-1), respectively. Calcium
      was required for activity on pectic substrates, whereas the addition of 1 mM
      ethylenediaminetetraacetic acid (EDTA) resulted in complete inhibition of the
      enzymes. These two enzymes represent the first pectate lyases isolated and
      characterized from a cold-adapted marine bacterium.

PMID- 11302502
TI  - Isolation and characterization of a mixotrophic sulfur-oxidizing Thermus
      scotoductus.
AB  - Thermophilic, faculatatively mixotrophic sulfur-oxidizing bacteria were isolated
      from a sulfide-rich, neutral hot spring in Iceland. The strain, IT-7254, used
      thiosulfate and elemental sulfur as electron donors, oxygen and nitrate as
      electron acceptors, and acetate and other organic compounds as carbon sources.
      After a few days of growth in the presence of thiosulfate, this strain formed
      sulfur globules. Comparison of intracellular enzymes and heme proteins of
      heterotrophically and mixotrophically grown cells showed some differences. The
      new isolate belonged to Thermus scotoductus because the small subunit (SSU) rRNA
      gene sequence analysis showed 98.6% sequence similarity and 84% DNA:DNA
      reassociation to Thermus scotoductus NMX2 A. 1. It is also close to Thermus
      antranikianii HN3-7, with 98.3% and 79% SSU rRNA sequence similarity and DNA:DNA
      reassociation, respectively. It was also found that both Thermus NMX2 A.1 and T.
      antranikianii HN3-7 were able to oxidize thiosulfate but that the T. scotoductus
      type strain SE-1 was not. This is the first report of Thermus strains that are
      capable of mixotrophic growth with sulfur oxidation.

PMID- 11302503
TI  - Liposome-mediated DNA uptake and transient expression in Thermotoga.
AB  - We report here the successful application of a PCR-based method to detect genetic
      transformation of Thermotoga neapolitana and Thermotoga maritima. Plasmid vectors
      were constructed using pRQ7, an 846-bp plasmid found in Thermotoga species strain
      RQ7, which replicates by a rolling circle mechanism. The vector pJY1 was
      constructed by placing a gene encoding a thermostable chloramphenicol
      acetyltransferase from Stacphylococcus aureus under the control of the tac
      promoter and joining this with pRQ7 in a pBluescript vector. A second vector,
      pJY2, was similarly constructed using a gene encoding a kanamycin
      nucleotidyltransferase previously engineered for thermostability. Genetic
      transformation of T. neapolitana and T. maritima spheroplasts was achieved using
      cationic liposomes. The transforming DNA was detected in cells grown in liquid
      cultures using polymerase chain reaction amplification of the cat or kan genes.
      T. neapolitana could maintain pJY1 for at least 25 generations in liquid medium
      containing chloramphenicol. The pJY2 vector conferred kanamycin resistance to T.
      maritima cells grown in liquid culture. Isolation of stable transformants on
      solid media after 2-3 days of incubation at 77 degrees C was not possible with
      either vector, probably because of the instability of both vectors and
      antibiotics under these conditions. However, this transformation procedure
      provides, for the first time, a method to introduce DNA into this
      hyperthermophilic bacterium for potential applications such as targeted gene
      disruption analyses.

PMID- 11302504
TI  - Random sequence analysis of genomic DNA of an anaerobic, thermophilic, halophilic
      bacterium, Halothermothrix orenii.
AB  - A pBluescriptSK+ vector library consisting of 3.360 clones with an average insert
      size of 3.5 kb was constructed from the genome of Halothermothrix orenii, a
      halophilic and thermoanaerobic member of the family Haloanaerobiaceae. From both
      ends, 77 clones were sequenced using T3 and T7 vector primers generating 154
      sequence tags, representing approximately 85 kb of the genome. Comparison of
      sequence tags against the Gen-Bank database using BLASTX identified 66 known
      proteins and 15 conserved hypothetical proteins. The putative proteins included a
      V-ATPase, hydrogenases, and enzymes with potential for industrial applications.
      The overall G + C% of the codons used was 42.9% with a third-position G + C
      content of 38.6%. High levels of excess acidic amino acids were not detected in
      the putative proteins of H. orenii as compared to the mesophilic haloanaerobes.
      This lack may be the result of reduced activity of acidic, halophilic enzymes at
      high temperatures and intermediate salt concentrations.

PMID- 11302505
TI  - Evaluation using the GRADE strategy.

PMID- 11302506
TI  - Reading, writing, and doctoring--a literary introduction to clinical medicine
      group.

PMID- 11302507
TI  - The financial status of departments of family medicine at US medical schools.
AB  - BACKGROUND: This report examined the financial health of departments of family
      medicine in US allopathic medical schools. METHODS: We conducted a survey of
      departments of family medicine at US medical schools, using academic year 1997
      1998 as the index year. A total of 52 (46%) of medical schools that have a
      department of family medicine responded to the survey. The survey examined
      sources of revenue and categories of expenditures. Analysis assessed the overall
      financial status of departments at that period of time. RESULTS: Responding
      departments of family medicine received 32% of their funding from state or
      university sources and an additional 32% of funding from clinical services.
      Grants and hospital support comprised another 17% each. Departments in public
      institutions received higher levels of support from hospitals (22% of revenue
      versus 8% for private schools). The overall balance sheets for departments of
      family medicine showed that 56% of departments have financial reserves, while 19%
      had no reserves but no debt. Twenty-five percent of all departments were in debt,
      including 2% with debt exceeding $1 million. CONCLUSIONS: The majority of
      departments of family medicine remain fiscally healthy, but these departments are
      dependent on funds from state and medical school sources. A substantial
      proportion of departments are in debt. Lower levels of grant support and the
      difficulty in increasing clinical revenue may create future funding problems for
      primary care faculty as medical schools increase dependence on these sources of
      income.

PMID- 11302508
TI  - A day in the life...perspectives by a family practice intern.

PMID- 11302509
TI  - The Balint movement in America.
AB  - Michael Balint's (1896-1970) career evolultion from general practitioner (1918)
      to psychoanalyst (1926) and subsequently to general practitioner educator (1950)
      began at his home in Budapest and then moved from London to sites in the United
      States. His frequent visits to America, together with his wife Enid, were an
      influential force in promoting and training US-based Balint group leaders.
      Michael and Enid Balint's influence, together with the support of US physicians,
      South African physicians who became US citizens, and behavioral scientists, laid
      the foundation for the formation of an American Balint Society in 1990. The
      Society's educational and research efforts occurred primarily in family practice
      residencies and have grown over the past 10 years. The Society, is presently
      working to standardize credentialing of Balint group leaders to assure continued
      quality growth in the American Balint movement.

PMID- 11302510
TI  - The effect of a global multiculturalism track on cultural competence of
      preclinical medical students.
AB  - BACKGROUND: We evaluated the effect of an elective (the Global Multiculturalism
      Track), including international and domestic immersion experiences, on the
      cultural competence of preclinical medical students. METHODS: A self-assessment
      instrument was used to measure cultural competence, and it was administered to
      Track participants and nonparticipating class cohorts at the beginning and the
      end of the preclinical years. RESULTS: Track participants (n=26) had a higher
      level of cultural competence both at the beginning and at the end of the program.
      At the end of their second year, students participating in the Track had, for the
      first time, greater knowledge of certain aspects of local cultures, more
      tolerance of people of other cultures not speaking English, and more comfort with
      patients of these cultures, compared with non-Track participants. CONCLUSIONS:
      The results are based on a small sample size, but the suggestion that a
      multiculturalism track could provide a model for development of cultural
      competence warrants further research.

PMID- 11302511
TI  - Patients' perceptions of medical students in a longitudinal family medicine
      clerkship.
AB  - BACKGROUND: Although educational characteristics of ambulatory clinical
      environments are becoming clearer, less is known concerning patient opinions
      about participating in medical student instruction in ambulatory settings. Such
      perceptions may have an important influence on recruitment and retention of
      community faculty. METHODS: Surveys were administered to 121 patients seen by
      medical students during a longitudinal family medicine clerkship. The survey
      explored patients' opinions regarding the extent of direct student involvement in
      their care, students'competence, and patient feelings about participating in
      medical student instruction. RESULTS: Patients felt that students were highly
      involved in providing care and that they performed competently and
      professionally. Patients found participation in medical education enjoyable, not
      excessively time-consuming or disruptive, and believed that students'
      participation improved the quality of care they received. CONCLUSIONS: Patients
      in our family medicine clerkship do not have negative perceptions about their
      participation in medical student education. In fact, this study suggests that
      such participation may actually enhance patient satisfaction.

PMID- 11302512
TI  - Redefining the need for faculty in family medicine: results of a 5-year follow-up
      survey.
AB  - BACKGROUND AND OBJECTIVES: A study was conducted in 1994 to determine the need
      for faculty in family medicine. This paper reports a comparative follow-up study
      in 1999. METHODS: This follow-up study determined faculty positions filled in the
      last 5 years, new faculty positions currently available, replacement faculty
      positions currently available, and new faculty positions anticipated to be
      available in the next 3 years. In addition, comparisons were made with the
      previous study regarding time available for clinical, educational, and research
      activities. RESULTS: In the 1994 survey, respondents reported 496 open faculty
      positions and anticipated that 677 would become available during the subsequent 3
      years, for a total of 1,173 positions. The 1999 survey data indicated that the
      actual number of positions filled or still open since 1994 was 1,072. In
      contrast, new positions open in 1999 or anticipated to be open in the subsequent
      3 years were 604. For both residencies and departments, most positions in both
      surveys were for clinicians. CONCLUSIONS: Despite a decrease in the number of
      available positions for family medicine faculty reported between the 1994
      original survey and 1999 follow-up survey, there are still more than 600 faculty
      positions currently available, and additional new positions are anticipated over
      the next 3 years.

PMID- 11302513
TI  - From petting zoos to electronic classrooms: meeting the technology learning needs
      of family medicine teachers.
AB  - BACKGROUND AND OBJECTIVES: To meet the need for faculty development in the use of
      information technology for its membership, the Society of Teachers of Family
      Medicine (STFM) Program Committee implemented a pilot, fee-supported, electronic
      classroomformat at STFM's 2000 Annual Spring Conference. We assessed the
      characteristics of those who attended the sessions, the satisfaction of
      participants with the venue both from expressed satisfaction and enrollment, the
      financial viability of electronic classrooms, and whether participants used
      acquired skills 6 months after the conference. METHODS: An evaluation instrument
      was used to collect the demographic data on attendees and their satisfaction with
      the sessions they attended. This data was compiled and compared with the
      demographics of overall conference attendees. The enrollment and revenues for the
      electronic classrooms were totaled and compared with expenses. A 6-month post
      conference phone survey was conducted to assess continued use of learned skills.
      RESULTS: Attendees were more likely to be physicians from community-based
      residencies. The program was filled to 80% capacity. Survey results indicated
      that the program was satisfying to attendees. Registration fees covered costs.
      Most participants were still using their new skills 6 months after the program.
      CONCLUSIONS: The electronic classroom pilot was successful and provides skills
      that participants use months after the program. This program can be used to meet
      the educational technology training needs of STFM members.

PMID- 11302514
TI  - Predictors of patient referrals by primary care residents to specialty care
      clinics.
AB  - BACKGROUND AND OBJECTIVES: Physician referral patterns significantly impact
      costs, quality of care, and access to the health system. This paper examines
      factors predictive of patient referrals to specialists by primary care residents.
      METHODS: New adult patients (n=509) were randomly assigned to primary care
      residents at a university medical center. Patient referrals to specialists were
      monitored for 1 year of care. Self-reported patient health status,
      sociodemographic information, number of primary care visits, and physician
      practice style behaviors were incorporated into statistical analyses predicting
      specialty referrals. RESULTS: Patients who were referred to specialty care were
      significantly older, had poorer physical health, and saw their primary care
      physicians more often than patients who were not referred. Patients were most
      frequently referred to surgical specialty clinics. After controlling for physical
      health status, gender, and age, more frequent visits to a primary care resident
      physician who had a technically oriented style of care was associated with a
      greater total number of specialty clinic referrals. CONCLUSIONS: Patient
      variables, as well as physician practice style, have an important impact on the
      specialty referral process. Although the appropriateness of referrals was not
      evaluated, these findings have implications for health care delivery.

PMID- 11302515
TI  - Reliving the nightmare.

PMID- 11302516
TI  - Non-coding snoRNA host genes in Drosophila: expression strategies for
      modification guide snoRNAs.
AB  - Modification guide snoRNAs either are encoded within introns and co-transcribed
      with the host gene pre-mRNA or are independently transcribed as mono- or
      polycistronic units. Different eukaryotic kingdoms utilize these coding
      strategies to various degrees. Intron-encoded and polycistronic snoRNAs are
      released from primary transcripts as pre-snoRNAs by the spliceosome or by an
      RNase III-like activity, respectively. In the spliceosomal pathway, the resulting
      intron lariat is then linearized by a debranching activity. The leader and
      trailer sequences of pre-snoRNAs are removed by exonucleolytic activities. The
      majority of snoRNA host genes encode proteins involved in the synthesis,
      structure or function of the translational apparatus. Several vertebrate snoRNA
      host genes do not appear to code for functional proteins. We have identified two
      unusually compact box C/D multi-snoRNA host genes in D. melanogaster, dUHG1 and
      dUHG2, similar in their organization to the corresponding vertebrate non-protein
      coding host genes. In dUHG1 and dUHG2, the snoRNA sequences are located within
      introns at a conserved distance of about 75 nucleotides upstream of the 3' splice
      sites. Both genes initiate transcription with TOP-like sequences that share
      unique features with previously reported Drosophila snoRNA host genes. Although
      the spliced dUHG RNAs are relatively stable, they exhibit little potential for
      protein coding.

PMID- 11302517
TI  - Eci1p uses a PTS1 to enter peroxisomes: either its own or that of a partner,
      Dci1p.
AB  - Saccharomyces cerevisiae delta3,delta2-enoyl-CoA isomerase (Eci1p), encoded by
      ECI1, is an essential enzyme for the betaoxidation of unsaturated fatty acids. It
      has been reported, as well as confirmed in this study, to be a peroxisomal
      protein. Unlike many other peroxisomal proteins, Ecilp possesses both a
      peroxisome targeting signal type 1 (PTS1)-like signal at its carboxy-terminus (
      HRL) and a PTS2-like signal at its amino-terminus (RIEGPFFIIHL). We have found
      that peroxisomal targeting of a fusion protein consisting of Eci1p in front of
      green fluorescent protein (GFP) is not dependent on Pex7p (the PTS2 receptor),
      ruling out a PTS2 mechanism, but is dependent on Pex5p (the PTS1 receptor). This
      Pex5p-dependence was unexpected, since the putative PTS1 of Ecilp is not at the C
      terminus of the fusion protein; indeed, deletion of this signal (-HRL-) from the
      fusion did not affect the Pex5p-dependent targeting. Consistent with this, Pex5p
      interacted in two-hybrid assays with both Eci1p and Eci1PdeltaHRL. Ecilp-GFP
      targeting and Eci1pdeltaHRL interaction were abolished by replacement of Pex5p
      with Pex5p(N495K), a point-mutated Pex5p that specifically abolishes the PTS1
      protein import pathway. Thus, Eci1p peroxisomal targeting does require the Pex5p
      dependent PTS1 pathway, but does not require a PTS1 of its own. By disruption of
      ECI1 and DCI1, we found that Dci1p, a peroxisomal PTS1 protein that shares 50%
      identity with Eci1p, is necessary for Eci1p-GFP targeting. This suggests that the
      Pex5p-dependent import of Eci1p-GFP is due to interaction and co-import with
      Dci1p. Despite the dispensability of the C-terminal HRL for import in wild-type
      cells, we have also shown that this tripeptide can function as a PTS1, albeit
      rather weakly, and is essential for targeting in the absence of Dci1p. Thus,
      Eci1p can be targeted to peroxisomes by its own PTS1 or as a hetero-oligomer with
      Dcilp. These data demonstrate a novel, redundant targeting pathway for Eci1p.

PMID- 11302518
TI  - Electron tomography of mitochondria after the arrest of protein import associated
      with Tom19 depletion.
AB  - In a mutant form of Neurospora crassa, in which sheltered RIP (repeat induced
      point mutation) was used to deplete Tom19, protein transport through the TOM/TIM
      pathway is arrested by the addition of p-fluorophenylalanine (FPA). Using
      intermediate-voltage electron tomography, we have generated three-dimensional
      reconstructions of 28 FPA-treated mitochondria at four time points (0-32 h) after
      the addition of FPA. We determined that the cristae surface area and volume were
      lost in a roughly linear manner. A decrease in mitochondrial volume was not
      observed until after 16 h of FPA treatment. The inner boundary membrane did not
      appear to shrink or contract away from the outer membrane. Interestingly, the
      close apposition of these membranes remained over the entire periphery, even
      after all of the cristae had disappeared. The different dynamics of the shrinkage
      of cristae membrane and inner boundary membrane has implications for
      compartmentalization of electron transport proteins. Two structurally distinct
      types of contact sites were observed, consistent with recently published work. We
      determined that the cristae in the untreated (control) mitochondria are all
      lamellar. The cristae of FPA-treated mitochondria retain the lamellar morphology
      as they reduce in size and do not adopt tubular shapes. Importantly, the crista
      junctions exhibit tubular as well as slot-like connections to the inner boundary
      membrane, persisting until the cristae disappear, indicating that their stability
      is not dependent on continuous protein import through the complex containing
      Tom19.

PMID- 11302519
TI  - ERGIC-53 KKAA signal mediates endoplasmic reticulum retrieval in yeast.
AB  - Studies on the ERGIC-53 KKAA signal have revealed a new mechanism for static
      retention of mammalian proteins in the endoplasmic reticulum (Andersson, H.,
      Kappeler, F., Hauri, H. P. (1999): Protein targeting to endoplasmic reticulum by
      dilysine signals involves direct retention in addition to retrieval. J. Biol.
      Chem. 274,15080 - 15084). To test if this mechanism was conserved in yeast, the
      ERGIC-53 KKAA signal was transferred on two different yeast reporter proteins.
      Making use of a genetic assay, we demonstrate that this signal induces COPI
      dependent ER retrieval. ER retention of KKAA-tagged proteins was impaired in
      yeast mutants affected in COPI subunits. Furthermore, biochemical analysis of
      post-ER carbohydrate modifications detected on reporter proteins indicated that
      KKAA-tagged proteins recycle continuously within early compartments of the
      secretory pathway. Therefore in yeast, the KKAA signal might only function as a
      classical dilysine ER retrieval signal.

PMID- 11302520
TI  - Cdx1 promotes cellular growth of epithelial intestinal cells through induction of
      the secretory protein PAP I.
AB  - Expression of the Cdx1 homeobox gene in epithelial intestinal cells promotes
      cellular growth and differentiation. Cdx1and the Pancreatitis Associated Protein
      I (PAP I) are concomitantly expressed in the epithelial cells of the lower part
      of the intestinal crypts. Because Cdx1 is a transcription factor and PAP I, in
      other tissues, is a proliferative factor, we looked for a relationship between
      these two proteins in the intestinal-derived IEC-6 cells. After stable
      transfection with a Cdx1 expression vector, they produce high levels of the PAP I
      transcript and protein indicating a functional link between the two genes.
      Demonstration of Cdx1 binding to the PAP I promoter region and suppression of PAP
      I induction after deletion of the corresponding sequence indicated that Cdx1 is a
      transcription factor controlling PAP I gene expression in intestinal cells. By
      infecting IEC-6 cells with adenoviruses expressing PAP I, we demonstrated that
      PAP I induces mitosis in these cells. On the other hand, inhibition of the PAP I
      expression in the IEC-6 Cdxl-expressing cells using an antisense strategy
      confirmed the requirement of this protein for the effect of Cdx1 on cell growth.
      Finally, addition of the immunopurified PAP I to the culture medium promotes cell
      growth of the IEC-6 cells in a dose-dependent manner. Maximal effect was obtained
      at 1 ng/ml. Taken together these results demonstrate that PAP I is a target of
      the Cdx1 homeobox gene in intestinal cells which participates in the regulation
      of intestinal cell growth via an autocrine and/or paracrine mechanism.

PMID- 11302521
TI  - Plasmodium vivax and Plasmodium chabaudi: intraerythrocytic traffic of
      antigenically homologous proteins involves a brefeldin A-sensitive secretory
      pathway.
AB  - We have used a monoclonal antibody (mAb 7C5B71) raised against the erythrocytic
      stages of Plasmodium vivax to identify a 148-kDa P vivax protein antigen (Pv-148)
      which crossreacts with an antigenically homologous 190-kDa protein of P. chabaudi
      (Pc-190). During parasite intraerythrocytic development Pv-148 and Pc-190 are
      exported into the host cell cytosol and become located in the surface membrane of
      the infected erythrocyte. Immunofluorescence confocal microscopy and
      immunoelectron microscopy studies showed that both Pv-148 and Pc-190 are released
      from the parasite and exported to the host cell cytoplasm in association with
      tubovesicular membrane (TVM) structures. Fluorescent in vivo labelling of P.
      chabaudi with Bodipy-ceramide followed by immunofluorescence staining with the
      mAb supported the association of antigenically homologous Pc-190 with TVM
      structures. In the presence of brefeldin A (BFA), secretion of antigenically
      homologous Pc-190 into the host cell cytoplasm was inhibited and the antigen
      remained in the parasite cytoplasm. BFA also arrested the maturation of the
      parasite. Taken together these results suggest that Pv-148 and Pc-190 are related
      parasite proteins that are transported into the host cell through a BFA-sensitive
      secretory pathway.

PMID- 11302522
TI  - Beta2 integrin modulates platelet caspase activation and life span in mice.
AB  - We explored the role of CD18 (beta2 integrin) in platelet physiology, using mice
      genetically deficient in CD18 (CD18 -/-), or its main ligand CD54 (ICAM-1, CD54 
      /-). CD18 and CD11a were evident in platelets from +/+, but not from CD18 -/-
      mice, as seen by immunofluorescence or Western blots. CD18 mRNA was also
      detectable by RT-PCR in platelets from +/+, but not from CD18 -/- mice. The life
      span of platelets was significantly shorter in CD18 -/- than in +/+ or CD54 -/-
      mice, as seen by in vivo biotinylation. When a local inflammation was elicited by
      the intra-tracheal injection of TNF, labeled platelets from +/+, but not from
      CD18 -/- donors, did localize in the lung. The content of Bcl-3 was about 20-fold
      higher in platelet from CD18 -/-, than in those from +/+ or CD54 -/- donors, as
      seen on Western blots or by immunofluorescence and flow cytometry, while the
      amount of pro-caspase-3 was decreased. An activation of caspases in platelets
      from CD18 -/- was also evidenced by protease assays. Accordingly, gelsolin, a
      protein cleaved by caspase-3, showed a low-molecular-weight band in platelets
      from CD18 -/- but not from +/+ donors. These results demonstrate that the beta2
      integrin, present in mouse platelets, modulates caspase activation and
      consequently platelet life span and response to TNF.

PMID- 11302523
TI  - Uptake of endocytic markers by rice cells: variations related to the growth
      phase.
AB  - Endocytosis is now considered a basic cellular process common to plant cells.
      Although both non-specific and receptor-mediated endocytosis appear to take place
      in plant cells, the physiological role of the latter remains unclear. We have
      investigated the endocytic process in rice cell suspensions using two
      biotinylated proteins, peroxidase and bovine serum albumin (bHRP and bBSA), as
      markers. First, we show that markers are internalized by rice cells and appear in
      intracellular membranes. The uptake of the two markers is temperature dependent,
      saturable with time and markers dose and it is competed by free biotin. Thus, it
      shows the properties of a receptor-mediated process. We also show that uptake of
      markers is strongly influenced by growth phase as optimal uptake occurs during
      the lag phase, but the initiation of the exponential growth phase decreases
      uptake drastically. Arrest of the cell cycle by starvation of either a nutrient
      (phosphate) or a growth regulator (2,4-dichlorophenoxyacetic acid), both
      components of the culture medium, does not modify the rate of bBSA uptake.
      Subsequent readdition of these components results in growth recovery and a
      dramatic decrease in bBSA uptake. On the other hand, nocodazole treatment, a
      method to arrest the cell cycle by microtubule depolymerization, inhibited bBSA
      uptake. The possible causes for this arrest of endocytosis are discussed.

PMID- 11302524
TI  - Changes in cell volume and internal sodium concentration in HeLa cells during
      exponential growth and following lonidamine treatment.
AB  - Cell volumes decreased in HeLa cells as a function of time after seeding during
      exponential growth. Cell volume distributions revealed the presence of two cell
      populations in all stages of growth. When cells approached confluence, the ratio
      of the two populations abruptly shifted towards that characterised by the
      smallest volume. Percentages of G1-, S- and G2 + M-phase cells were also measured
      and it was found that G1 frequency increased as a function of cell density during
      exponential growth. Intracellular sodium concentration, [Na]i was monitored by
      23Na NMR in the presence of 5 mM dysprosium (III) tripolyphosphate. [Na]i
      increased from 22.8 to 59.0 mM in cells from the second to the seventh day after
      seeding. Treatment with lonidamine, an antitumoral drug that it is known to slow
      down cell growth by affecting aerobic glycolysis, produced a complete block of
      cell progression after a few days of treatment. The progression of cell volume
      distributions towards smaller volumes and the increase in internal sodium
      concentration as a function of time after seeding were also affected by the drug.
      These phenomena were related to the existence of a subpopulation of mitotically
      inactive G1-phase cells during exponential growth, pointing out that a density
      dependent cellular mechanism regulates the cell cycling in HeLa cells.

PMID- 11302525
TI  - The ROP-syntaxin interaction inhibits neurotransmitter release.

PMID- 11302526
TI  - Pulmonary receptors in reptiles: discharge patterns of receptor populations in
      snakes versus turtles.
AB  - This study examines the effects of lung inflation/deflation with and without CO2
      on the entire population of pulmonary receptors in the vagus nerve in two species
      of snakes and two species of turtles. We asked the question, "how does the
      response of the entire mixed population of pulmonary stretch receptors (PSR) and
      intrapulmonary chemoreceptors (IPC) in species possessing both differ from that
      in species with only PSR"? This was studied under conditions of artificial
      ventilation with the secondary goal of extending observations on the
      presence/absence of IPC to a further three species. Our results indirectly
      illustrate the presence of IPC in the Burmese python and South American
      rattlesnake but not the side necked turtle, adding support to the hypothesis that
      IPC first arose in diapsid reptiles. In both species of snake, CO2-sensitive
      discharge (presumably from IPC) predominated almost to the exclusion of CO2
      insensitive discharge (presumably arising from PSR) while the opposite was true
      for both species of turtle. The data suggest that for animals breathing air under
      conditions of normal metabolism there is little to distinguish between the
      discharge profiles of the total population of receptors arising from the lungs in
      the different groups. Interestingly, however, under conditions of elevated
      environmental CO2 most volume-related feedback from the lungs is abolished in the
      two species of snakes, while under conditions of elevated metabolic CO2, it is
      estimated that volume feedback from the lungs would be enhanced in these same
      species.

PMID- 11302527
TI  - A test of the hypothesis that T3 is the "seasonality" thyroid hormone in American
      tree sparrows (Spizella arborea): intracerebroventricular infusion of iopanoic
      acid, an inhibitor of T3 synthesis and degradation.
AB  - This study tested the hypothesis that L-3,5,3'-triiodothyronine (T3) is the
      bioactive "seasonality" thyroid hormone in American tree sparrows (Spizella
      (arborea). The experimental approach coupled thyroid hormone replacement therapy
      after radiothyroidectomy with photostimulation and intracerebroventricular
      infusion of iopanoic acid, an inhibitor of L-3,5,3'-triiodothyronine synthesis
      and degradation. Endpoints were testis length, molt score, and hypothalamic
      content of chicken gonadotropin-releasing hormone 1. The hypothesis predicts that
      thyroidectomized male tree sparrows moved to long days and given thyroxine in
      combination with iopanoic acid will lack L-3,5,3'-triiodothyronine and so will
      not express thyroid hormone-dependent photoperiodic testicular growth (a vernal
      component of seasonality) and photorefractoriness or postnuptial molt (autumnal
      components of seasonality). It further predicts that iopanoic acid will enhance
      the efficacy of L-3,5,3'-triiodothyronine and so will facilitate the expression
      of seasonality in thyroidectomized males given L-3,5,3'-triiodothyronine
      replacement therapy. Iopanoic acid had no significant effect on any component of
      seasonality in thyroid-intact males given vehicle, or in thyroidectomized males
      given thyroxine or L-3,5,3'-triiodothyronine. Thyroid-intact males, as well as
      thyroidectomized males infused with thyroxine alone, commonly expressed all
      components of seasonality. Thyroidectomized males given L-3,5,3'-triiodothyronine
      alone exhibited photoperiodic testicular growth, but did not become
      photorefractory or initiate molt. While these results confirm that thyroid
      hormone acts centrally to program American tree sparrows for seasonality, they do
      not support the hypothesis that L-3,5,3'-triiodothyronine is the bioactive
      "seasonality" thyroid hormone, and they challenge the view that thyroxine is
      merely a prohormone.

PMID- 11302528
TI  - Water relations during desiccation of cysts of the potato-cyst nematode Globodera
      rostochiensis.
AB  - The loss during desiccation of osmotically active water (OAW), which freezes
      during cooling to -45 degrees C, and osmotically inactive water (OIW), which
      remains unfrozen, from the cysts of the potato cyst nematode, Globodera
      rostochiensis, was determined using differential scanning calorimetry. Exotherms
      and endotherms associated with non-egg compartments were not detected after 5 min
      desiccation at 50% relative humidity and 20 degrees C. The pattern of water loss
      from the cysts indicates that water is lost from compartments outside the eggs
      first, that nearly all the non-egg water is OAW and that the OIW content of the
      cyst is contained within the eggs. Water is lost from the eggs only after the OAW
      content outside the eggs falls below that within the eggs. Both OAW and OIW are
      lost from the eggs during desiccation but the eggs retain a small amount of OIW.
      Other animals which survive some desiccation but which are not anhydrobiotic will
      tolerate the loss of OAW but not the loss of their OIW. Anhydrobiotic animals can
      survive the loss of both their OAW and a substantial proportion of their OIW.

PMID- 11302529
TI  - The development of diving in marine endotherms: preparing the skeletal muscles of
      dolphins, penguins, and seals for activity during submergence.
AB  - Myoglobin is an important oxygen store for supporting aerobic diving in
      endotherms, yet little is known about its role during postnatal development.
      Therefore, we compared the postnatal development of myoglobin in marine
      endotherms that develop at sea (cetaceans) to those that develop on land
      (penguins and pinnipeds). We measured myoglobin concentrations in the major
      locomotor muscles of mature and immature bottlenose dolphins (Tursiops truncatus)
      and king penguins (Aptenodytes patagonicus) and compared the data to previously
      reported values for northern elephant seals (Mirounga angustirostris). Neonatal
      dolphins, penguins, and seals lack the myoglobin concentrations required for
      prolonged dive durations, having 10%, 9%, and 31% of adult values, respectively.
      Myoglobin contents increased significantly during subsequent development. The
      increases in myoglobin content with age may correspond to increases in activity
      levels, thermal demands, and time spent in apnea during swimming and diving.
      Across these phylogenetically diverse taxa (cetaceans, penguins, and pinnipeds),
      the final stage of postnatal development of myoglobin occurs during the
      initiation of independent foraging, regardless of whether development takes place
      at sea or on land.

PMID- 11302530
TI  - Differential effect of cold acclimation on blood composition in rats and
      hamsters.
AB  - Male rats and hamsters were exposed to a progressively lower air temperature and
      shorter photoperiod to simulate the onset of winter. Normothermic hamsters had a
      higher haematological oxygen carrying capacity (OCC) and coagulability (shorter
      prothrombin time and activated partial thromboplastin time) than rats. Cold
      acclimation significantly increased the OCC of rats, which parallels an increased
      metabolic rate, while no differences were observed in hamsters. Red cell transit
      time through filters was faster in the acclimated rats but not in hamsters,
      reflecting the lower mean cell volume due to a decreased rate of clearance from
      the circulation. Platelet counts were significantly lower in both cold-acclimated
      rats and hamsters, and there was a significant leucopenia in rats, which would
      reduce the degree of microvascular blockade. Whole blood viscosity, plasma
      viscosity, and serum osmolarity showed little change in either species. However,
      whole blood viscosity was significantly lower in cold-acclimated hamsters than
      control hamsters at the lowest shear rate tested (0.95 s(-1)). Interestingly,
      plasma viscosity and serum osmolarity were significantly lower in hamsters
      exposed to low temperatures for a shorter period (4 weeks), and may reflect the
      development of a reduced coagulability. These data suggest that blood composition
      in hamsters contributes to an innate tolerance of low temperatures, maintaining
      tissue perfusion under hypothermic conditions and aiding arousal from
      hibernation.

PMID- 11302531
TI  - Morphometry and estimated bulk oxygen diffusion in larvae of Xenopus laevis under
      chronic carbon monoxide exposure.
AB  - To understand the mechanisms that allow tadpoles of the African clawed frog
      Xenopus laevis to develop under conditions of impaired convective transport
      (hemoglobin poisoning with carbon monoxide), whole animal surface area and volume
      were measured and bulk oxygen diffusion was modeled at four developmental stages
      (from initiation of heartbeat to pre-metamorphic climax). Surface area [8.5 mm2
      at stages Nieuwkoop-Faber (NF) 33-34 to 70.2 mm2 at stages NF 50-51] and volume
      (1.8 mm3 at stages NF 33-34 to 35.7 mm3 at stages NF 50-51) measured from
      volumetric analysis from dual plane images of each animal were not significantly
      different between treatments. Bulk oxygen radial diffusion was estimated by
      modeling the larvae as a set of adjacent cylinders with different radii. The
      model was used to predict the oxygen tension at the water-skin interface at which
      the oxygen tension in the center of the animal is nil (0.7 kPa at stage NF 33-34
      and 14.0 kPa at stage NF 50-51), suggesting that bulk oxygen diffusion is
      sufficient to meet the metabolic demand up to stages NF 46-47 irrespective of the
      oxygen tension at the water-skin interface. At NF 50-51 an anoxic core in the
      animal would appear if bulk oxygen diffusion were the only means of oxygen
      transport at oxygen tensions below 15 kPa. However, the relative volume of the
      anoxic core would only exceed 10% of the total volume of the animal only at
      oxygen tensions below 5 kPa. Therefore, the ten-fold increase in mass between NF
      50-51 and metamorphosis would prove insufficient for embryonic oxygen
      requirements via simple diffusion, and therefore would require additional
      transport mechanisms.

PMID- 11302532
TI  - Placental nutrition in the Tasmanian skink, Niveoscincus ocellatus.
AB  - Niveoscincus ocellatus is an important species in historical analyses of the
      evolution of viviparity because it is the species upon which the type II
      chorioallantoic placenta was based. Here we describe the net nutrient uptake
      across the placenta of N. ocellatus for comparison with other species of skinks
      with complex placentae. N. ocellatus is highly placentotrophic, with neonates
      being 1.68-times larger in dry matter than the fresh eggs. There is an increase
      of nitrogen from 6.3 +/- 0.2 mg to 9.2 +/- 0.6 mg, and ash from 3.8 +/- 0.3 mg to
      6.7 +/- 0.6 mg. The increase in ash is made up by a more than two-fold increase
      in the amounts of calcium, potassium and sodium. There is no significant
      difference in lipids in the neonates compared to fresh eggs, so considerable
      lipid must have crossed the placenta to provide energy for embryonic development.
      N. ocellatus is significantly more placentotrophic than Niveoscincus metallicus,
      which also has a complex chorioallantoic placenta. Discovery of substantial
      placentotrophy in this genus confirms that two lineages of Australian lygosomine
      skinks (represented by the genera Pseudemoia and Niveoscincus) have evolved this
      pattern of embryonic nutrition and supports the hypothesis that the evolution of
      reptilian placentotrophy involves specialisations in addition to structural
      modifications of the chorioallantoic placenta.

PMID- 11302533
TI  - Biochemical and physiological evidence that bile acids produced and released by
      lake char (Salvelinus namaycush) function as chemical signals.
AB  - It has been hypothesized that faeces of juvenile lake char (Salvelinus namaycush)
      may contain chemical cues that mediate behaviour of conspecifics. However, our
      knowledge of bile acids naturally produced and released by fish is limited. Using
      HPLC, we fractionated bile acids produced and released by lake char and examined
      their stimulatory effectiveness using electro-olfactogram recordings. Taurocholic
      acid, taurochenodeoxycholic acid, taurooxocholanic acid, taurooxodeoxycholic acid
      3alpha-sulphate, trace amounts of taurolithocholic acid and an unidentified
      sulphated bile steroid were found in bile and faeces. Bile acids were either
      taurine amidated or sulphated, or both. Lake char released an average of 4 nmol
      min(-1) bile acids per kilogram of body weight into their tank water. Urinary
      bile acids accounted for only a small portion of total bile acids released into
      water. Water and faeces contained higher proportion of taurochenodeoxycholic acid
      and sulphated bile acids (relative to taurocholic acid) than bile. The electro
      olfactogram recordings demonstrated that bile acids released by lake char were
      detectable by their olfactory system at nanomolar concentrations, which is well
      below the levels of bile acids released into water. The exquisite olfactory
      sensitivity of lake char to water-borne bile acids released by their conspecifics
      is consistent with a role for these compounds as important chemical signals.

PMID- 11302534
TI  - Cold acclimation increases basal heart rate but decreases its thermal tolerance
      in rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss, Walbaum) were acclimated to 4 degrees C and
      17 degrees C for more than 4 weeks and heart rate was determined in the absence
      and presence of adrenaline to see how thermal adaptation influences basal heart
      rate and its beta-adrenergic control in a eurythermal fish species. The basal
      heart rate in vitro was higher in cold-acclimated than warm-acclimated rainbow
      trout at temperatures below 17 degrees C. On the other hand, adaptation to cold
      decreased thermal tolerance of heart rate so that the maximal heart rates were
      achieved at 17 degrees C (75 +/- 4 bpm) and 24 degrees C (88 +/- 2 bpm) in cold
      acclimated and warm-acclimated trout, respectively. Beta-adrenergic response of
      the heart was enhanced by cold-adaptation, since adrenaline (100 nmol l(-1))
      caused stronger stimulation of heart rate in cold-acclimated (29 +/- 14%) than in
      warm-acclimated fish (10 +/- 1%; P = 0.03). Furthermore, adrenaline strongly
      opposed the temperature-dependent deterioration of force production in cold
      acclimated trout but not in warm-acclimated trout. The results indicate that
      adaptation to cold increases basal heart rate but decreases its thermal tolerance
      in rainbow trout. Cold acclimation up-regulates the beta-adrenergic system, and
      beta-adrenoceptor activation seems to provide cardioprotection against high
      temperatures in the cold-adapted rainbow trout.

PMID- 11302535
TI  - Ca++ regulation of paracellular permeability in the middle intestine of the eel,
      Anguilla anguilla.
AB  - The role of Ca++ on the regulation of the paracellular pathway permeability of
      the middle intestine of Anguilla anguilla was studied by measuring the
      transepithelial resistance and the dilution potential, generated when one half of
      NaCl in the mucosal solution was substituted iso-osmotically with mannitol, in
      various experimental conditions altering extracellular and/or intracellular
      calcium levels. We found that removal of Ca++ in the presence of ethylene glycol
      bis(beta-aminoethyl ether) (EGTA) from both the mucosal and the serosal side, but
      not from one side only, reduced both the transepithelial resistance and the
      magnitude of the dilution potential. The irreversibility of this effect suggests
      a destruction of the organization of the junction in the nominal absence of Ca++.
      However a modulatory role of extracellular Ca++ cannot be excluded. The decrease
      of the intracellular Ca++ activity, produced by using verapamil to block the Ca++
      entry into the cell, or by adding 3,4,5-trimethoxybenzoic acid 8-(diethylamino)
      octyl ester (hydrochloride) (TMB-8), an inhibitor of Ca++ release from the
      intracellular stores, reduced both the transepithelial resistance and the
      magnitude of the dilution potential, indicating a role of cytosolic Ca++ in the
      modulation of the paracellular permeability. However the rise of calcium activity
      produced by the Ca++ ionophore calcimycin (A23187) evoked an identical effect,
      suggesting that any change in physiological intracellular Ca++ activity alters
      the paracellular permeability.

PMID- 11302536
TI  - Family origin and the response of threespine stickleback, Gasterosteus aculeatus,
      to thermal acclimation.
AB  - To establish whether family origin affects the response of the threespine
      stickleback (Gasterosteus aculeatus) to thermal acclimation, we examined the
      rates of feeding, growth, and food conversion, relative tissue and organ masses
      and activities of a mitochondrial and a glycolytic enzyme in pectoral and axial
      muscle of individually housed fish from six families during acclimation to 8
      degrees C and 23 degrees C. Feeding rates differed among families but were
      consistently higher in warm-acclimated than cold-acclimated fish. Growth rates
      differed among families. In four families growth was greater at 8 degrees C;
      these families generally had higher conversion efficiencies at 8 degrees C than
      23 degrees C. For two families, growth was greater at 23 degrees C than 8 degrees
      C and conversion efficiencies did not differ between 8 degrees C and 23 degrees
      C. Relative tissue and organ masses (percent axial muscle, hepatosomatic, gut and
      kidney indices) differed with gender and among families (hepatosomatic, gut and
      kidney indices) but little with acclimation status. In all families and in both
      muscles, activities of the mitochondrial enzyme, citrate synthase (CS), were
      increased by cold acclimation. Axial muscle levels of the glycolytic enzyme,
      lactate dehydrogenase (LDH), were not affected by thermal acclimation or family
      origin, but were strongly correlated with the hepatosomatic index and axial
      muscle protein content. Pectoral muscle levels of LDH were affected by family
      origin which also influenced the response to thermal acclimation. Similar
      patterns were observed for specific activities and total muscle contents of these
      enzymes. Stickleback family origin influenced rates of feeding and growth and the
      thermal sensitivity of growth rates but not the compensatory increase in muscle
      CS levels with cold acclimation. The differing thermal sensitivities of growth
      could reflect distinct strategies for the timing of juvenile growth.

PMID- 11302537
TI  - Caring within nursing education: a metasynthesis.
AB  - During the 1990s qualitative research studies on caring within schools of nursing
      have been conducted. What generalizations can be made from these qualitative
      research studies that can effectively be used to promote the development of a
      caring community in nursing education in the 21st century? A metasynthesis of 14
      qualitative research studies on caring among faculty and students was conducted.
      Noblit and Hare's metaethnographic approach was used. The metasynthesis revealed
      five metaphors or themes that permeated caring in nursing education. These
      metaphors centered on reciprocal connecting that consisted of presencing,
      sharing, supporting, competence, and uplifting effects of caring. Implications of
      this metasynthesis for nursing educators are addressed.

PMID- 11302538
TI  - The U.S. Air Force pilot simulated medical unit: a teaching strategy with
      multiple applications.
AB  - Historically, Air Force military hospitals have provided excellent training
      platforms for students and nurses to remain proficient and ready to deliver
      competent care in a war-time environment. Because of a decrease in the number of
      admissions, the opportunity to maintain competence is diminishing. The concept of
      a Simulated Medical Unit (SMU) is being developed at Sheppard Air Force Base,
      Wichita Falls, Texas to assist in the training and evaluation of such skills. The
      SMU is a simulation of an actual enactment of an inpatient unit that begins with
      shift report to the oncoming nursing team. The instructor can then guide the
      student and team through a series of complex situations using specialized
      mannequins and live actors as "patients." The student is expected to carry out
      physicians' orders, perform nursing assessments, document nursing care, as well
      as administer medications and IV fluids. Scenarios can be made to be as simple or
      as complex as the situation demands and can be adapted to any specialty. The
      student can practice technical know-how, sharpen critical thinking abilities, and
      exercise delegation skills. Should an error occur, the instructor can freeze the
      moment and assist the student in developing more appropriate choices in their
      delivery of care. The use of algorithms, performance checklists, and videotaping
      can be used to evaluate the student's performance. Other adaptations for the SMU
      can include orientation, cross training into different specialties, competency
      assessment, and upgrade training.

PMID- 11302539
TI  - Self-directed learning: faculty and student perceptions.
AB  - This article reports the results of a qualitative study that explored faculty and
      student perceptions of self-directed learning (SDL) and investigated factors that
      facilitate or impede it. This study was conducted at McMaster University with
      faculty and students in a 4-year undergraduate nursing program. Data were
      collected from 47 faculty and 17 students by means of focus groups that were
      audiotaped and transcribed. Content analysis was conducted to identify common
      themes in faculty and student transcripts. The themes that emerged provide
      insight into the educational strategy of self-directed learning and can be
      summarized by the following major points: (1) commitment to SDL requires students
      and faculty to understand the value of empowering learners to take increased
      responsibility for decisions related to learning; (2) students engaged in self
      directed learning undergo a transformation that begins with negative feelings
      (i.e., confusion, frustration, and dissatisfaction) and ends with confidence and
      skills for lifelong learning; and (3) faculty development is important to ensure
      high levels of competency in facilitating self-directed learning.

PMID- 11302540
TI  - Academic misconduct: responses from deans and nurse educators.
AB  - The purpose of this study was to describe what deans/chairs and faculty in
      baccalaureate nursing programs perceive as academic misconduct among students.
      Subjects were asked to describe a positive and negative incident that reflected
      student cheating and/or plagiarizing and to describe the setting where the
      incident occurred. Various types of cheating and plagiarism were described by the
      subjects as occurring in the classroom setting. In the clinical setting,
      incidents of false documentation and faked home visits were reported. Results of
      this study support the need for a clearer understanding among students of what
      constitutes plagiarism. Students who become involved in academic misconduct need
      to be identified early and policies must be developed that will assist
      administrators and faculty in dealing with these issues.

PMID- 11302541
TI  - New partnerships between education and practice: precepting junior nursing
      students in the acute care setting.

PMID- 11302542
TI  - The clinical notebook: using student portfolios to enhance clinical teaching
      learning.

PMID- 11302543
TI  - Teaching blood pressure measurement: CD-ROM versus conventional classroom
      instruction.

PMID- 11302544
TI  - Changing answers on multiple-choice examinations taken by baccalaureate nursing
      students.

PMID- 11302545
TI  - Resolving the nursing shortage: replacement plus one!

PMID- 11302546
TI  - Historical and current perspectives on bone marrow transplantation for prevention
      and treatment of immunodeficiencies and autoimmunities.
AB  - Primary immunodeficiency diseases often fully meet the definition of "experiments
      of nature." Much of the expanding understanding of the lymphoid systems and
      immunologic functions generated in recent years has been derived from studying
      patients with primary, generally genetically determined immunodeficiency
      diseases, as well as other relatively rare secondary immunodeficiency diseases.
      Increasing knowledge of immunologic defenses, their interacting cellular and
      molecular components, the evolving details of sequential stages of cellular
      differentiation, and the nature and control of the cellular and molecular
      interactions in immunity have now made it possible to define precisely many
      primary immunodeficiency diseases in full molecular genetic terms. With this
      wealth of scientific information based on experimental and clinical research,
      incredible advances have also been made in using bone marrow transplantation
      (BMT) often as a curative treatment for immunodeficiency, some 60 to 70 other
      diseases, leukemias, lymphomas, other cancers, and a rapidly expanding
      constellation of metabolic diseases or enzyme deficiencies. Also, progress in
      applying allogeneic BMT to prevent, treat, and cure complex autoimmune diseases,
      primary immunodeficiency diseases and certain forms of cancers, is considered.
      Further, mixed BMT (syngeneic plus allogeneic) that establishes a form of stable
      mixed chimerism has also been employed in animal experiments, which revealed that
      BMT can be used to treat not only immunodeficiency diseases, but also systemic
      and organ-specific autoimmune diseases, eg, diabetes and erythematous lupus-like
      diseases. Moreover, performing BMT in conjunction with organ allografts, eg,
      thymus or pancreatic transplants, has successfully prevented rejection of these
      allografts, sometimes without recourse to long-term irradiation or toxic chemical
      immunosuppressive agents. A crucial role for stromal cells in cellular
      engineering has now also been realized in animal models as a means of preventing
      graft rejection and promoting full and persistent reconstitution or correction of
      genetically-based diseases. With all of these achievements, BMT promises
      continued dramatic and impressive new approaches to clinical and scientific
      research and reveals an attractive strategy for the treatment and prevention of
      many currently intractable human diseases. If these achievements can be extended
      to larger outbred animals and humans, BMT may set the stage for induction of
      improved immunologic tolerance and for developing treatments for additional
      intractable human diseases in the 21st century.

PMID- 11302547
TI  - Antibodies to CD40 induce a lethal cytokine cascade after syngeneic bone marrow
      transplantation.
AB  - CD40 stimulation, by either antibody or ligand, has been shown to inhibit the
      growth of a variety of neoplastic cells, both in vivo and in vitro. In this
      study, we assessed the effects of CD40 stimulation using a murine agonistic CD40
      monoclonal antibody (MoAb) (FGK115) or a soluble recombinant murine CD40 ligand
      (srmCD40L) in both lethally irradiated and nonirradiated BALB/c mice. Toxicity
      after CD40 stimulation was not observed in nonirradiated animals receiving up to
      100 microg of the agonist anti-CD40 MoAb. However, as little as 10 microg of the
      agonistic anti-CD40 MoAb induced acute toxicity resulting in 100% morbidity of
      lethally irradiated animals by 4 days after irradiation. Histological evaluation
      of animals receiving anti-CD40 MoAb revealed severe intestinal lesions with
      disruption of the villi, goblet cell depletion, and crypt hyperplasia of the
      small intestine, colon, and cecum. Delaying the administration of anti-CD40 MoAb
      or reducing the amount of irradiation given resulted in increased survival and
      less severe lesions. Analysis of serum cytokine levels in lethally irradiated
      mice receiving agonistic anti-CD40 showed a marked increase of interferon (IFN)
      gamma. Lethally irradiated IFN-gamma knockout mice given the agonistic anti-CD40
      MoAb demonstrated significant increases in survival and minimal gut lesions
      compared with wild-type mice receiving the same regimen, suggesting that IFN
      gamma plays a major role in this toxic reaction. These results indicate that CD40
      stimulation using agonistic antibodies following lethal irradiation leads to a
      fatal, cytokine-induced disease affecting the intestine.

PMID- 11302548
TI  - Induction of tolerance by mixed chimerism with nonmyeloblative host conditioning:
      the importance of overcoming intrathymic alloresistance.
AB  - A nonmyeloablative conditioning regimen, consisting of depleting doses of anti
      CD4 and anti-CD8 monoclonal antibodies (MoAbs) given on days -6 and -1 and 3 Gy
      of whole body irradiation given on day 0, allows the engraftment of fully major
      histocompatibility complex (MHC)-mismatched allogeneic bone marrow and the
      induction of tolerance for the graft. If MoAbs are given on day -5 only,
      permanent chimerism and tolerance are not observed in most animals. The addition
      of thymic irradiation to the single MoAb treatment permits tolerance induction in
      these mice, suggesting that residual host thymocytes reject donor marrow in
      recipients of 1, but not 2, MoAb injections. In this study, both CD4+ and CD8+
      thymocytes were found to be responsible for residual alloreactivity in mice
      receiving only 1 MoAb injection. Co-receptor coating and downmodulation on
      residual thymocytes occur to a greater extent in recipients of 2 MoAb injections
      than in recipients of a single MoAb injection. This downmodulation may play a
      role in the loss of alloreactivity. Our results suggest that a second MoAb
      injection inactivates mature, functional donor-alloreactive CD4+ and CD8+ host
      thymocytes.

PMID- 11302549
TI  - Secondary failure of platelet recovery after hematopoietic stem cell
      transplantation.
AB  - After primary recovery of platelet counts after transplantation, there can be a
      late persistent decline called secondary failure of platelet recovery (SFPR),
      which may occur although the counts of other cell lineages remain within the
      normal range. SFPR was defined as a decline of platelet counts below
      20,000/microL for 7 consecutive days or requiring transfusion support after
      achieving sustained platelet counts > or = 50,000/microL without transfusions for
      7 consecutive days after hematopoietic stem cell transplantation (HSCT). The
      study population consisted of 2871 consecutive patients receiving transplants
      from January 1990 to March 1997. After primary recovery of platelet counts, SFPR
      not due to relapse of the underlying disease was observed in 285 of 1401 (20%)
      patients undergoing allogeneic transplantation and 36 (8%) of 444 patients
      undergoing autologous transplantation, with a median time of onset after
      transplantation at day 63 (range, day 21-156) and day 44 (range, day 24-89),
      respectively. Concomitant neutropenia was seen in 57 (20%) of 285 patients
      undergoing allogeneic HSCT and 7 (19%) of 36 patients undergoing autologous HSCT
      with SFPR. By multivariable analysis, the following were factors significantly
      associated with SFPR after allogeneic HSCT: a transplant from an unrelated donor;
      a graft-versus-host disease (GVHD) prophylaxis other than methotrexate and
      cyclosporine; development of grade 2 through 4 acute GVHD; impaired renal or
      liver function; conditioning with the combination of busulfan, cyclophosphamide,
      and total body irradiation; stem cell dose; and infections. Cytomegalovirus
      infection after engraftment and source of stem cells were the only significant
      risk factors after autologous HSCT. The hazard rate of death was significantly
      higher in patients who experienced SFPR (hazard ratio = 2.6 for allogeneic HSCT;
      hazard ratio = 2.2 for autologous HSCT). SFPR was associated with serious
      complications and poor outcome after transplantation. The identification of the
      characteristics and risk factors for SFPR could improve patient counseling and
      management and lead to the design of effective treatment strategies.

PMID- 11302550
TI  - Relapse after allogeneic bone marrow transplantation for refractory anemia is
      increased by shielding lungs and liver during total body irradiation.
AB  - Patients with the refractory anemia (RA) subtype of myelodysplastic syndrome who
      undergo allogeneic bone marrow transplantation (BMT) have a low risk of relapse,
      but they have a high risk of nonrelapse mortality when prepared with conventional
      preparative regimens. To try to reduce nonrelapse mortality, we treated 14 RA
      patients with a modified approach to total body irradiation (TBI) followed by
      cyclophosphamide (CY) and HLA-identical sibling BMT. Median patient age was 44
      years (range, 28 to 65 years). Patients received TBI with shielding of the right
      lobe of the liver and both lungs followed by electron beam boosts to shielded
      ribs. Total radiation exposure in nonshielded areas was 12 Gy (n = 10), 10 Gy (n
      = 3), or 6 Gy (n = 1). After TBI, patients received CY at 120 mg/kg over 2 days,
      followed by transplantation of unmanipulated bone marrow. All patients initially
      achieved engraftment with donor cells, although 2 patients had subsequent
      reemergence of host hematopoiesis without evidence of disease relapse. Five
      patients died of transplantation-related causes between 22 and 1262 days post
      BMT. Four patients relapsed between 157 and 1096 days post-BMT. These 14 patients
      were compared with 46 historical controls with RA who received conventional
      CY/TBI or busulfan/CY preparative regimens. Patients in the experimental group
      had a similar nonrelapse mortality rate compared with the historical control
      group (29% versus 37%, respectively; P = .8), but a higher relapse rate (34%
      versus 2%, P = .0004) and a lower disease-free survival (38% versus 61%, P =
      .16). We conclude that this modified TBI approach is associated with an
      unacceptably high risk of relapse for patients with RA undergoing BMT.

PMID- 11302551
TI  - Vaccination against infectious disease following hematopoietic stem cell
      transplantation.
AB  - Patients undergoing hematopoietic stem cell transplantation (HSCT) experience a
      prolonged period of dysfunctional immunity associated with an increased risk of
      bacterial and viral infections. Effective approaches toward vaccinating patients
      against common pathogens are being explored but are limited by poor levels of
      responsiveness. Relevant studies examining the nature of reconstitution of
      cellular and humoral immunity and its impact on vaccination strategies against
      infectious pathogens are reviewed. Following transplantation, deficiencies in
      cellular immunity are characterized by the inversion of CD4/CD8 ratios, a
      decreased proliferative response to mitogens, and the development of anergy to
      recall antigens as measured by delayed-type hypersensitivity testing. The impact
      on humoral immunity consists of decreased levels of circulating immunoglobulin,
      impaired immunoglobulin class switching, and a loss of complexity in
      immunoglobulin gene rearrangement patterns. In this setting, a loss of protective
      immunity has been demonstrated against viral and bacterial pathogens previously
      targeted by childhood vaccination. Infections due to encapsulated bacterial
      organisms such as Streptococcus pneumoniae and Haemophilus influenzae type B
      remain prevalent even in the late posttransplantation period. The efficacy of
      vaccination following HSCT is influenced by the time elapsed since
      transplantation, the nature of the hematopoietic graft, the use of serial
      immunization, and the presence of graft-versus-host disease. Strategies to
      enhance vaccine efficacy include pretransplantation immunization of the stem cell
      donor and the use of cytokine adjuvants.

PMID- 11302552
TI  - MPer1 and mper2 are essential for normal resetting of the circadian clock.
AB  - Mammalian Per1 and Per2 genes are involved in the mechanism of the circadian
      clock and are inducible by light. A light pulse can evoke a change in the onset
      of wheel-running activity in mice by shifting the onset of activity to earlier
      times (phase advance) or later times (phase delays) thereby advancing or delaying
      the clock (clock resetting). To assess the role of mouse Per (mPer) genes in
      circadian clock resetting, mice carrying mutant mPer1 or mPer2 genes were tested
      for responses to a light pulse at ZT 14 and ZT 22, respectively. The authors
      found that mPer1 mutants did not advance and mPer2 mutants did not delay the
      clock. They conclude that the mammalian Per genes are not only light-responsive
      components of the circadian oscillator but also are involved in resetting of the
      circadian clock.

PMID- 11302553
TI  - Assembling a clock for all seasons: are there M and E oscillators in the genes?
AB  - The hypothesis is advanced that the circadian pacemaker in the mammalian
      suprachiasmatic nucleus (SCN) is composed at the molecular level of a
      nonredundant double complex of circadian genes (per1, cry1, and per2, cry2). Each
      one of these sets would be sufficient for the maintenance of endogenous
      rhythmicity and thus constitute an oscillator. Each would have slightly different
      temporal dynamics and light responses. The per1/cry1 oscillator is accelerated by
      light and decelerated by darkness and thereby tracks dawn when day length
      changes. The per2 /cry2 oscillator is decelerated by light and accelerated by
      darkness and thereby tracks dusk. These M (morning) and E (evening) oscillators
      would give rise to the SCN's neuronal activity in an M and an E component.
      Suppression of behavioral activity by SCN activity in nocturnal mammals would
      give rise to adaptive tuning of the endogenous behavioral program to day length.
      The proposition-which is a specification of Pittendrigh and Daan's E-M oscillator
      model-yields specific nonintuitive predictions amenable to experimental testing
      in animals with mutations of circadian genes.

PMID- 11302554
TI  - Modeling the molecular calendar.

PMID- 11302555
TI  - Phase response curves of a molecular model oscillator: implications for mutual
      coupling of paired oscillators.
AB  - Increasing evidence indicates that the accessory medulla is the circadian
      pacemaker controlling locomotor activity rhythms in insects. A prominent group of
      neurons of this neuropil shows immunoreactivity to the peptide pigment-dispersing
      hormone (PDH). In Drosophila melanogaster, the PDH-immunoreactive (PDH-ir)
      lateral neurons, which also express the clock genes period and timeless, are
      assumed to be circadian pacemaker cells themselves. In other insects, such as
      Leucophaea maderae, a subset of apparently homologue PDH-ir cells is a candidate
      for the circadian coupling pathway of the bilaterally symmetric clocks. Although
      knowledge about molecular mechanisms of the circadian clockwork is increasing
      rapidly, very little is known about mechanisms of circadian coupling. The authors
      used a computer model, based on the molecular feedback loop of the clock genes in
      D. melanogaster, to test the hypothesis that release of PDH is involved in the
      coupling between bilaterally paired oscillators. They can show that a combination
      of all-delay- and all-advance-type interactions between two model oscillators
      matches best the experimental findings on mutual pacemaker coupling in L.
      maderae. The model predicts that PDH affects the phosphorylation rate of clock
      genes and that in addition to PDH, another neuroactive substance is involved in
      the coupling pathway, via an all-advance type of interaction. The model suggests
      that PDH and light pulses, represented by two distinct classes of phase response
      curves, have different targets in the oscillatory feedback loop and are,
      therefore, likely to act in separate input pathways to the clock.

PMID- 11302556
TI  - Circadian organization in male mice lacking the gene for endothelial nitric oxide
      synthase (eNOS-/-).
AB  - Circadian (approximately 24 h) rhythms in physiology and behavior are generated
      by the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus. For
      these endogenous rhythms to be synchronized with the external environment, light
      information must be transmitted to pacemaker cells within the SCN. This
      transmission of light information is accomplished via a direct retino
      hypothalamic tract (RHT). Nitric oxide (NO), an endogenous gas that functions as
      a neurotransmitter, has been implicated as a messenger necessary for photic
      entrainment. Three isoforms of the enzyme that form NO, NO synthase, have been
      identified (a) in neurons (nNOS), (b) in the endothelial lining of blood vessels
      (eNOS), and (c) as an inducible form in macrophages (iNOS). The present study was
      undertaken to determine the specific role of eNOS in circadian organization and
      photic entrainment. Wild-type (WT) and eNOS-/- mice were initially entrained to a
      14:10 light:dark (LD) cycle. After 3 weeks, the LD cycle was phase advanced.
      After an additional 3 weeks, animals were held in constant darkness (DD). eNOS-/-
      animals did not exhibit a deficit in the ability to entrain to the LD cycle,
      phase-shift locomotor activity, or free-run in constant conditions. Animals held
      in DD were killed after light exposure during either the subjective day or the
      subjective night to assess c-fos induction in the SCN. Light exposure during the
      subjective night increased c-fos protein expression in the SCN of both WT and
      eNOS-/- mice relative to animals killed after light exposure during the
      subjective day. Taken together, these findings suggest that endothelial isoform
      of NOS may not be necessary for photic entrainment in mice.

PMID- 11302557
TI  - Phase response curve and light-induced fos expression in the suprachiasmatic
      nucleus and adjacent hypothalamus of Arvicanthis niloticus.
AB  - This article describes the phase response curve (PRC), the effect of light on Fos
      immunoreactivity (Fos-IR) in the suprachiasmatic nucleus (SCN), and the effect of
      SCN lesions on circadian rhythms in the murid rodent, Arvicanthis niloticus. In
      this species, all individuals are diurnal when housed without a running wheel,
      but running in a wheel induces a nocturnal pattern in some individuals. First,
      the authors characterized the PRC in animals with either the nocturnal or diurnal
      pattern. Both groups of animals were less affected by light during the middle of
      the subjective day than during the night and were phase delayed and phase
      advanced by pulses in the early and late subjective night, respectively. Second,
      the authors characterized the Fos response to light at circadian times 5, 14, or
      22. Light induced an increase in Fos-IR within the SCN during the subjective
      night but not subjective day; this effect was especially pronounced in the
      ventral SCN, where retinal inputs are most concentrated, but was also evident in
      other regions. Both light and time influenced Fos-IR within the lower
      subparaventricular area. Third, SCN lesions caused animals to become arrhythmic
      when housed in a light-dark cycle as well as constant darkness. In summary,
      Arvicanthis appear to be very similar to nocturnal rodents with respect to their
      PRC, temporal patterns of light-induced Fos expression in the SCN, and the
      effects of SCN lesions on activity rhythms.

PMID- 11302558
TI  - Patterns of wheel running are related to Fos expression in neuropeptide-Y
      containing neurons in the intergeniculate leaflet of Arvicanthis niloticus.
AB  - A variety of nonphotic influences on circadian rhythms have been documented in
      mammals. In hamsters, one such influence, running in a novel wheel, is mediated
      in part by the pathway extending from neuropeptide-Y (NPY)-containing cells
      within the intergeniculate leaflet (IGL) of the thalamus to the hypothalamic
      suprachiasmatic nucleus (SCN). Arvicanthis niloticus is a species in which all
      individuals are diurnal with respect to general activity and body temperature
      when they are housed without a running wheel, but access to a running wheel
      induces a subset of individuals to become nocturnal. In the first study, the
      authors evaluated the possibility that nocturnal and diurnal patterns of wheel
      running in Arvicanthis are correlated with differences in IGL function. Adult
      male Arvicanthis housed in a 12:12 light-dark (LD) cycle were monitored in
      wheels, classified as nocturnal or diurnal, and then perfused either 4 h after
      lights-on or 4 h after lights-off. Sections through the intergeniculate leaflet
      were processed for immunohistochemical labeling of Fos and NPY. The percentage of
      NPY cells that expressed Fos was significantly influenced by an interaction
      between time of day and phenotype such that it rose from night to day in diurnal
      animals, and from day to night in nocturnal animals. In the second experiment,
      the authors established that running in a wheel actually induces Fos in the IGL
      of Arvicanthis. Specifically, the proportion of NPY cells expressing Fos was
      increased by access to wheels in nocturnal animals at night and in diurnal
      animals during the day. In the third experiment, the authors established that
      lesions of the IGL eliminate NPY fibers within the SCN, suggesting that these IGL
      cells project to the SCN in this species as has been established in other
      rodents. Together, these data demonstrate a clear difference in NPY cell function
      in nocturnal and diurnal Arvicanthis that appears to be caused, at least in part,
      by the differences in their wheel-running patterns, and that NPY cells within the
      IGL project to the SCN in Arvicanthis.

PMID- 11302559
TI  - Relationship between norepinephrine release in the hypothalamic paraventricular
      nucleus and circulating prolactin levels in the Siberian hamster: role of
      photoperiod and the pineal gland.
AB  - The impact of norepinephrine (NE) and its metabolite, 3-methoxy4
      hydroxyphenylglycol (MHPG), on circulating prolactin (PRL) was evaluated in the
      paraventricular region of the hypothalamus as a function of photoperiod and
      integrity of the pineal gland. In Experiment 1, whole tissue content of NE and
      MHPG was assessed in male and female hamsters that had been pinealectomized or
      sham-pinealectomized and exposed to long or short photoperiods for 5 weeks. The
      results revealed a marginal effect of photoperiod in males, but no overall
      effects of surgery. Because analysis of whole tissue content can be complicated
      by concurrent changes in synthesis and storage rates, Experiment 2 was conducted
      using microdialysis to assess extracellular levels of NE and MHPG in female
      hamsters. Pinealectomy completely prevented the short-day-induced suppression of
      luteinizing hormone, but it only partially prevented the effects of short days on
      PRL. Furthermore, both NE and MHPG levels were significantly elevated in short
      day-exposed pinealectomized and sham-operated animals. These results suggest that
      NE release within the paraventricular nucleus inhibits the circulating PRL levels
      and is one mechanism by which direct photic information can influence the
      neuroendocrine axis independently of the pineal melatonin signal.

PMID- 11302560
TI  - Is self-reported morbidity related to the circadian clock?
AB  - Morningness and eveningness preference, an endogenous component of the circadian
      clock, is characterized by an interindividual difference in circadian phase and
      requires of humans a specific timing of behavior. The biological rhythms of
      morning and evening types are consequently phase shifted with fixed socioeconomic
      constraints. The impact of this phase shift on health is widely debated. The
      purpose of the authors' study was to determine the influence of
      morningness/eveningness preference on self-reported morbidity and health in an
      active population. A total of 1165 nonshift workers of the French national
      electrical and gas company, enrolled in the GAZEL cohort and aged 51.3+/-3.3
      years, were included in this study. They replied by mail with a completed
      questionnaire, including morningness/eveningness preference, self-reported
      morbidity, subjective sleep patterns, and daytime somnolence and sleeping
      schedules for 3 weeks, during the spring of 1997. Annual self-reported health
      impairments were assessed with the annual general questionnaire of the GAZEL
      cohort for 1997. After adjustment for age, sex, and occupational status,
      morningness-like and eveningness-like participants reported a specific worse self
      reported morbidity. Whereas morningness was associated with worse sleep (p =
      0.0001), eveningness was associated with feeling less energetic (p = 0.04) and
      physical mobility (p = 0.02). These relationships were observed even in good
      sleepers, except for physical mobility. After adjustment for confounding
      variables, eveningness-like participants reported more sleep (p = 0.0004) and
      mood (p = 0.00018) disorders than morningness-like participants.
      Morningness/eveningness preference was related to specific chronic complaints of
      insomnia: morningness was related with difficulty in maintaining sleep (p =
      0.0005) and the impossibility to return to sleep in the early morning (p =
      0.0001) (sleep phase-advance syndrome); eveningness was related to difficulty in
      initiating sleep (p = 0.0001) and morning sleepiness (p = 0.0001). In good
      sleepers, morningness was related with sleep phase-advance syndrome (p = 0.0001)
      and eveningness with morning sleepiness (p = 0.0001). In conclusion, the
      expression (phase advance or delay) of the circadian clock could be related to
      worse self-reported morbidity and health. These findings must be verified by
      further epidemiological studies, but they suggest that the impossibility to
      return to sleep in the early morning is not only associated with age.

PMID- 11302561
TI  - How to fix the "review process".

PMID- 11302562
TI  - Show me the data!

PMID- 11302563
TI  - Serotonin, norepinephrine and dopamine involvement in the antidepressant action
      of hypericum perforatum.
AB  - Hypericum perforatum is considered an effective alternative to the synthetic
      antidepressants in the treatment of mild-to-moderate depression. Recently, we
      showed that the effects on neurotransmitter contents in different brain regions
      of laboratory animals are more evident after administration of hypericum extracts
      containing a higher concentration of flavonoids, thus suggesting that these
      compounds are important in the antidepressant action of hypericum perforatum. We
      studied the effects of Ph-50, a hypericum extract standardized to flavonoids
      (50%) and containing 0.3% hypericin and 4.5% hyperforin on brain serotonin
      content, norepinephrine and dopamine by a high-performance liquid chromatography
      method in discrete brain areas (cortex, diencephalon and brainstem) in male
      Sprague-Dawley rats. Moreover, we evaluated the effects of Ph-50 alone or in
      association with sulpiride (a dopamine receptor antagonist), metergoline (a
      serotonin receptor antagonist) and 6-hydroxydopamine (6-OH-DA, destroying
      norepinephrine-containing neurons) using a forced-swimming test in the rat.
      Hypericum extract (Ph-50; 250-500 mg/kg) with acute oral administration enhanced
      serotonin, norepinephrine and dopamine content in the brain and reduced the
      immobility time of rats in the forced-swimming test. Sulpiride, metergoline and 6
      OH-DA significantly increased the period of immobility in the forced-swimming
      test for the rats receiving hypericum extract (Ph-50). The results indicate that
      the neurotransmitters studied could be involved in the anti-immobility effects of
      hypericum, and suggest that its antidepressant action is probably mediated by
      serotonergic, noradrenergic and dopaminergic system activation.

PMID- 11302564
TI  - Polysomnographic effects of adjuvant ginkgo biloba therapy in patients with major
      depression medicated with trimipramine.
AB  - Sleep disturbance and cognitive impairment are frequent complaints of depressed
      patients under standard antidepressant medication. Therefore, additional
      therapies are required which specifically focus on the improvement of these
      deficits without exerting major side effects. Ginkgo biloba extract (EGb) has
      been shown to improve cognitive abilities in elderly subjects and in patients
      with disorders of the dementia spectrum. Animal studies surmise that EGb may
      reduce CRH activity, which is substantially related to depressive mood and
      behavior, predominantly cognition and sleep. An open non-randomized pilot study
      has been conducted to investigate the effects of ginkgo biloba extract (EGb Li
      1370) on cognitive performance and sleep regulation in depressed inpatients. 16
      patients were treated with a trimipramine (T)-monotherapy (200 mg) for six weeks.
      In eight of the 16 patients, an adjunct EGb therapy (240 mg/d) was applied for
      four weeks after a baseline week, the other eight patients remained on
      trimipramine monotherapy (200 mg) during the entire study. Polysomnography,
      cognitive psychomotor performance and psychopathology were assessed at baseline,
      after short-term and long-term adjunct EGb treatment, and after one week of
      ginkgo discontinuation (at the respective evaluation times in the eight patients
      on T-monotherapy). This report focuses on the results of EGb on sleep EEG
      pattern. EGb significantly improved sleep pattern by an increase of sleep
      efficiency and a reduction of awakenings. In addition, sleep stage 1 and REM
      density were reduced, while stage 2 was increased. Non-REM sleep, predominantly
      slow wave sleep in the first sleep cycle, was significantly enhanced compared to
      trimipramine monotherapy. Discontinuation of EGb reversed most of these effects.
      Based on the animal data, these results suggest that EGb may improve sleep
      continuity and enhance Non-REM sleep due to a weakening of tonic CRH-activity.
      The compensation of the deficient Non-REM component in depression by the EGb
      application may provide a new additional treatment strategy, especially in the
      treatment of the depressive syndrome with sleep disturbance.

PMID- 11302565
TI  - Differential effects of trimipramine and fluoxetine on sleep in geriatric
      depression.
AB  - The effects of trimipramine, a tricyclic antidepressant (TCA) with atypical
      pharmacological properties, and fluoxetine, a selective serotonine reuptake
      inhibitor (SSRI), were compared in an exploratory analysis using mood and
      polysomnographic parameters during a six-week double-blind trial in 19 depressed
      geriatric patients. In sleep EEG measures, trimipramine demonstrated clear-cut
      effects on sleep measures resulting in higher values for sleep efficiency, total
      sleep time, stage 2 sleep, and shorter wake time. Under fluoxetine treatment, the
      proportion of REM sleep was decreased and REM latency was lengthened, whereas no
      change in REM sleep parameters was observed in the trimipramine group. The
      present data suggest that early antidepressant effects of medication occur
      independently of drug-induced changes in objective measures of sleep, i.e.
      suppression of REM sleep.

PMID- 11302566
TI  - Psychopathological correlates of reduced dopamine receptor sensitivity in
      depression, schizophrenia, and opiate and alcohol dependence.
AB  - A dysfunction of central dopaminergic neurotransmission has been found in various
      neuropsychiatric diseases, and may be associated with a common psychopathological
      correlate. One hypothesis suggests that dopaminergic stimulation of the brain
      reward system reinforces behavior because it is experienced as pleasurable, and
      that dopaminergic dysfunction leads to anhedonia, the inability to experience
      pleasure. An alternative hypothesis assumes that dopaminergic stimulation does
      not promote pleasure or "liking" of a reward but rather mediates "wanting" of a
      reward, and suggests that dopaminergic dysfunction is associated with a failure
      to be motivated by stimuli that indicate reward. We measured negative symptoms,
      psychomotor slowing and dopamine receptor sensitivity in twelve drug-free
      patients with major depression, seventeen alcohol-dependent and sixteen opiate
      dependent patients, ten schizophrenics with neuroleptic medication, and ten
      healthy controls. The sensitivity of central dopamine receptors was assessed with
      the growth hormone response to apomorphine application. Psychomotor slowing was
      measured in a reaction-time test and anhedonia and other negative symptoms were
      assessed with self-rating scales and the Scale for the Assessment of Negative
      Symptoms. Patients with major depression, alcohol dependence and neuroleptic
      medication displayed a reduced sensitivity of central dopamine receptors compared
      to control subjects. Anhedonia was not a common correlate of dopamine receptor
      dysfunction. Instead, affective flattening was associated with both dopamine
      receptor sensitivity and psychomotor slowing. Our findings thus do not support
      the anhedonia hypothesis of central dopaminergic dysfunction. Rather, affective
      flattening may result from the lack of an emotional response towards reward
      indicating stimuli. These findings indicate that patients with dopaminergic
      dysfunction are not unable to experience pleasure, but may fail to be motivated
      by environmental stimuli to seek reward.

PMID- 11302567
TI  - Effects of risperidone on event-related potentials in schizophrenic patients.
AB  - In order to examine the effects of risperidone on cognitive impairment in
      schizophrenia, event-related potentials (ERPs) were recorded before and after
      switching from conventional neuroleptics to risperidone in schizophrenic
      patients. ERPs were recorded during two auditory discrimination tasks (an oddball
      task and a distraction task) in 10 medicated schizophrenic patients during
      conventional neuroleptic and risperidone treatments. The amplitudes and latencies
      of N 100 and P300 component were measured in ERPs for target stimuli in the
      oddball task and in ERPs for target and novel stimuli in the distraction task.
      Although N 100 amplitude and latency and P 300 amplitude did not change
      significantly after switching the drug compared to that during conventional
      neuroleptic treatment, P 300 latency for target stimuli shortened significantly
      during risperidone treatment in both tasks, accompanied by the shortening of the
      reaction time in the distraction task. The P 300 latency change did not correlate
      with the change of the severity of psychopathology. These findings suggest that
      risperidone may speed the information processing in schizophrenic patients,
      contributing to the improvement of cognitive functions.

PMID- 11302568
TI  - Atypical antipsychotics in bipolar and schizoaffective disorders.
AB  - No data are available comparing the relative efficacy of different atypical
      agents in patients with bipolar disorder. A chart review of bipolar and
      schizoaffective disorder patients who had received courses of at least two
      atypical agents (n = 33) in a community psychiatry system was conducted. No
      differences in rates of hospitalizations were found between individual atypical
      agents or between atypical agents as a class and conventional neuroleptics.
      However, a significant reduction in rates of emergency room visits was found with
      atypical agents compared to conventional neuroleptics, with a trend toward
      greater reduction with clozapine compared to other atypical antipsychotics.
      Larger prospective studies are needed to confirm these preliminary observations.

PMID- 11302569
TI  - Moclobemide in pregnancy.
AB  - We report on the case of female patient with chronic dysthymia, who took
      moclobemide at 300 mg/day throughout her first pregnancy. The course of pregnancy
      was healthy, and natural delivery was uneventful. The psychomotoric and somatic
      development of the child within first 14 months of life has been normal.

PMID- 11302570
TI  - Biosynthesis and release of methylarsenic compounds during the growth of
      freshwater algae.
AB  - Arsenic transformations by freshwater algae have been studied under laboratory
      conditions. By the use of a new analytical method, we identified
      methylarsenic(III) species in the growth medium of green-alga Closterium
      aciculare incubated under axenic conditions. The arsenate concentration in the
      experimental medium began to decrease just after inoculation, and the levels of
      arsenite and methylarsenicals increased with the growth of C. aciculare.
      Initially, most of the arsenate was converted into arsenite, which peaked in
      concentration during the exponential phase. Methylarsenicals accumulated rapidly
      in the stationary phase. DMAA(V) production was enhanced when the ratio of
      phosphate to arsenate decreased in the culture medium. The levels of DMAA(V)
      increased continuously toward the end of the experiment. On the other hand,
      methylarsenic(III) species remained relatively steady during the stationary
      phase. Methylarsenic(III) species accounted for 0-35% of methylarsenicals. These
      results suggest that arsenite and methylarsenicals (containing methylarsenic(III)
      species) are supplied by phytoplankton, and serve as evidence of the origin of
      methylarsenic(III) species in natural waters.

PMID- 11302571
TI  - Biodegradation of phenanthrene in river sediment.
AB  - The aerobic biodegradation potential of phenanthrene (a polycyclic aromatic
      hydrocarbon [PAH]) in river sediment was investigated in the laboratory.
      Biodegradation rate constants (k1) and half-lives (t1/2) for phenanthrene (5
      microg/g) in sediment samples collected at five sites along the Keelung River in
      densely populated northern Taiwan ranged from 0.12 to 1.13 l/day and 0.61 to 5.78
      day, respectively. Higher biodegradation rate constants were noted in the absence
      of sediment. Two of the sediment samples were capable of biodegrading
      phenanthrene at initial concentrations 5-100 microg/g; lower biodegradation rates
      occurred at higher concentrations. Optimal biodegradation conditions were
      determined as 30 degreesC and pH 7.0. Biodegradation was not significantly
      influenced by the addition of such carbon sources as acetate, pyruvate, and yeast
      extract, but was significantly influenced by the addition of ammonium, sulfate,
      and phosphate. Results show that anthracene, fluorene, and pyrene biodegradation
      was enhanced by the presence of phenanthrene, but that phenanthrene treatment did
      not induce benzo[a]pyrene biodegradation during a 12-day incubation period.

PMID- 11302572
TI  - Subfractionation, characterization and photooxidation of crude oil resins.
AB  - Resins of five crude oils were obtained using SARA fractionation. The maltenic
      fraction of Blend Arabian Light, was further separated into six polar fractions.
      These fractions which are the constituents of the resins were analysed by FTIR
      spectroscopy. They appeared to be more oxidized, more aliphatic and less aromatic
      than asphaltenes. Photooxidation of resins showed that they are easily oxidizable
      and much more influenced by photooxidation than asphaltenes. The principal effect
      of photooxidation are: (i) increase of carbonyl group amounts and particularly
      formation of carboxylic groups, (ii) oxidation of sulfoxide in sulfone group,
      (iii) oxidation of alkyl chains and of aromatic rings (quinone structures).

PMID- 11302573
TI  - Aeolian flux of metals in Taiwan in the past 2600 years.
AB  - To identify anthropogenic sources of pollution, it is useful to compare recent
      and historical data, yet unfortunately such data are lacking in Taiwan. Thus, we
      studied the sediments deposited in the remote anoxic, subalpine Great Ghost Lake
      over a time span of 2600 yrs. Not only could a baseline be established, but also
      natural variations could be identified. Aeolian Asian dust particles seem to have
      played a significant role in the flux of 26 elements (Al, As, Ba, Br, Ca, Cd, Ce,
      Cl, Cr, Cs, Cu, Fe, Ga, K, Mg, Mn, Na, Ni, Pb, Rb, Si, Sr, Ti, V, Zn and Zr) in
      Great Ghost Lake. The fluxes have generally been higher during dry periods,
      especially since 1350 AD. On the other hand, local pollution from lead seems to
      have gained importance since 1945 AD. Recent aeolian fluxes were also calculated
      based on sediment data, and those results agree with direct measurements obtained
      in the region.

PMID- 11302574
TI  - Partial order ranking-based QSAr's: estimation of solubilities and octanol-water
      partitioning.
AB  - Partial order ranking appears as an attractive alternative to conventional
      Quantitative Structure Activity Relationships (QSAR) methods, the latter
      typically relying on the application of statistical methods. The method seems
      attractive as a priori knowledge of specific functional relationships is not
      required. In the present study, it is demonstrated that QSAR models based on a
      partial order ranking approach can be used satisfactorily to predict solubilities
      and octanol-water partitioning for a selection of organic compounds exhibiting
      different structural and electronic characteristics. The uncertainty is validated
      using well-established LSER descriptors. Two requirements to the model with
      regard to precision prevail, i.e., the model must be able to rank the single
      compounds in the basis set correctly compared to the experimental data, and the
      model should be based on a basis set of compounds large enough to secure a
      satisfactorily fine-meshed net, taking the number of descriptors into account. In
      the present study, the model was able to rank 318 out of 319 comparisons
      correctly in the case of solubilities. The corresponding figures for the octanol
      water partitioning were 407 out of 408. The precision and the uncertainties of
      the method which, were found closely related to the mutual interplay between the
      number of compounds and the number of descriptors is discussed in terms of the
      number of descriptors and compounds involved. The limitations of the method are
      discussed.

PMID- 11302575
TI  - Pesticides in precipitation in the Gdansk region (Poland).
AB  - Selected organonitrogen, organophosphorus and organochlorine pesticides have been
      determined in precipitation samples collected at 10 sites in the Gdansk region
      (northern Poland) over a period of one year (1998). Compounds which were detected
      most often included simazine (0.11-5.80 ng/l), fenitrothion (0.1-2.10 ng/l),
      chlorfenvinfos (0.1-1.30 ng/l), gamma-HCH (0.012-5.06 ng/l), heptachlor epoxide
      (0.05-3.28 ng/l) and aldrin (0.02-3.28 ng/l). The pesticide concentrations in
      precipitation samples revealed seasonal fluctuations, with higher concentrations
      observed during the application periods (June and July). The concentrations
      observed were also affected by the inflow of polluted air masses from the
      southwest. The total pesticide concentration in the precipitation samples was
      strongly related to the abundance of green areas in the vicinity of the sampling
      sites. A weak correlation was also found between the total concentration of
      organonitrogen and organophosphorus pesticides, and the total concentration of
      organochlorine pesticides in the samples collected.

PMID- 11302576
TI  - Seasonal and spatial variations of carbon and nitrogen distribution in the
      surface sediments of the Gulf of Riga, Baltic Sea.
AB  - The variations in concentrations of carbon and nitrogen in surface sediments of
      the Gulf of Riga were investigated between December 1993 and January 1995. The
      sediment samples were taken nine times during this period at two sampling sites.
      One sampling site, G5, exhibited high abundance of burrowing amphipods, whereas
      at the second site, T3, the number of macrozoobenthic organisms was comparatively
      small. Similar vertical profiles of mean sediment dry-weight concentrations of
      total carbon (TC) and total nitrogen (TN) were obtained at both sites G5 and T3.
      However, during autumn winter considerable differences of TC and TN
      concentrations in surface sediments (0-2 cm) between sites were observed. This
      was probably the effect of differences in the bioturbation level. During summer,
      when decline in numbers of amphipods were recorded, the vertical profiles of TC
      and TN at site G5 were similar to those at site T3. Significant differences
      between months were detected for TN at site T3 reflecting sedimentation of spring
      and autumn blooms in April and late October-early November, respectively. This
      was supported also by lower atomic C/N ratios in surface sediments during
      corresponding sampling events.

PMID- 11302577
TI  - Bioconcentration of the insecticide pyridaphenthion by the green algae Chlorella
      saccharophila.
AB  - A study was undertaken to examine the uptake of the organophosphate insecticide
      pyridaphenthion in the chlorophyta Chlorella saccharophila. Algae cultures were
      exposed to the initial nominal concentration 10.0 mg l(-1) pyridaphention during
      seven days. The insecticide bioconcentrates in the biomass to the highest level
      of 441.5 +/- 25.9 mg kg(-1) on the fifth day of exposure and was followed by a
      decrease to 76.6 +/- 5.1 mg kg(-1) on the seventh day. A model was constructed to
      describe the dynamic process, which estimated a bioconcentration factor (BCF)
      equal to 28. The study demonstrates the potential of accumulation of
      pyridaphenthion in aquatic organisms and helps to expand the pyridaphenthion
      toxicity database. The replacement of fenitrothion by pyridaphenthion concerning
      their use in rice flooded cultures is discussed.

PMID- 11302578
TI  - Uptake and distribution of rare earth elements in rice seeds cultured in
      fertilizer solution of rare earth elements.
AB  - The uptake behavior of rare earth elements (REEs) under pot conditions using
      deionized water and a REE fertilizer solution as the culture media as well as the
      distribution of REEs in rice proteins were studied. The uptake of REEs in rice
      seeds increased dramatically after a lag period of approximately three days.
      Roots can accumulate a much higher content of REEs than germs and the resting
      seeds. The REE content in each water-soluble (albumin) and salt-soluble
      (globulin) component of the rice seeds accounted for 5-8% and 4-6% of the total
      REEs, respectively. However, there are less than 1.5% of the total REEs were
      found in the alcohol-soluble (prolamin) and acetic acid-soluble (glutelin)
      components. The high performance liquid chromatography (HPLC) in the gel
      permeation and the reserved-phase were used to monitor changes in the molecular
      weight distribution changes of the soluble proteins of rice seeds during
      germination after having been cultured in the same solution for seven days. No
      changes occurred in the prolamin, while a slight change occurred in the albumin,
      globulin and glutelin. Fractionation of the albumin of rice seeds cultured in a
      REE fertilizer solution on the Sephadex G-100 column indicated that REEs,
      especially Ce, La, Pr and Nd, were associated mainly with biological compounds of
      a molecular weight between 10,000 and 12,000.

PMID- 11302579
TI  - Monitoring priority pollutants in a sewage treatment process by dichloromethane
      extraction and triolein-semipermeable membrane device (SPMD).
AB  - Semipermeable membrane devices containing a neutral lipid triolein (triolein
      SPMD) and conventional dichloromethane extraction were used to monitor the
      presence and concentrations of priority organic pollutants in a sewage treatment
      process in Beijing, China. Both samples gave similar information on the presence
      of target PCB congeners, PAHs, Organochlorine pesticides and substituted benzenes
      in sewage at all sites. After 20 days' sampling, the concentrations of
      contaminants in triolein of SPMD were much higher than those in dichloromethane
      extracts, which resulted in easier analysis, improved the detection limits, and
      increased the accuracy. Previous field mean sampling rates for SPMD were used to
      estimate concentrations of PCB congeners in sewage, which compared to their
      determined concentrations by dichloromethane extraction. The consistency and
      superiority of SPMD technology were proved for the detection of priority organic
      contaminants from sewage. Lower removal rates for PCB congeners and PAHs
      coincided with the persistence of them in environment. More attention should be
      paid to urban sewage treatment process adopting activated-sludge method, where
      priority organic pollutants might not be removed, even present higher
      concentrations after treatment.

PMID- 11302580
TI  - Mobility of atrazine from alginate-bentonite controlled release formulations in
      layered soil.
AB  - The mobility of atrazine [6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4
      diamine] from alginate-bentonite-based controlled release (CR) formulations was
      investigated by using soil columns. Two CR formulations based on sodium alginate
      (14.0 g kg(-1), atrazine (6.0 g kg(-1), natural or acid-treated bentonite (50 g
      kg(-1), and water (924 g kg(-1) were compared to technical grade product and
      commercial liquid (CL) formulation (Gesaprim 500FW). All herbicide treatments
      were applied to duplicate layered bed systems simulating the typical arrangement
      under a plastic greenhouse, which is composed of sand (10 cm), peat (2 cm),
      amended soil (20 cm) and native soil (20 cm). The columns were leached with 39 cm
      (1500 ml) and 156 cm (6000 ml) of 0.02 M CaCl2 solution to evaluate the effect of
      water volume applied on herbicide movement. When 39 cm of 0.02 M CaCl2 solution
      was applied, there was no presence of herbicide in the leachate for the alginate
      bentonite CR treatments. However, 0.11% and 0.14% of atrazine appeared in the
      leachate when the treatment was carried out with technical grade and CL
      formulations, respectively. When 156 cm of 0.02 M CaCl2 solution was applied, the
      use of the alginate-acid treated bentonite CR formulation retards and reduces the
      presence of atrazine in the leachate as compared to technical product. Analysis
      of the soil columns showed the highest atrazine concentration in the peat layer.
      Alginate-bentonite CR formulations might be an efficient system for reducing
      atrazine leaching in layered soil and thus, it could reduce the risks of
      pollution of groundwater.

PMID- 11302581
TI  - Determination of the levels of aromatic amines in indoor and outdoor air in
      Italy.
AB  - We studied the concentration of 10 primary aromatic amines (AA), which are
      classified as suspected carcinogens, in indoor and outdoor air in Italy. The
      measured AA included: aniline, o-toluidine, m-toluidine, p-toluidine, 2,3
      dimethylaniline, 2,4-dimethylaniline, 2,5-dimethylaniline, 2,6-dimethylaniline, 2
      naphtylamine and 4-aminobiphenyl. In the indoor environment (homes, offices and
      public buildings) the level of contamination (expressed as sum of 9 AA, excluding
      aniline) varied from 3 ng/m3 (hospital ward) to 207 ng/m3 (discotheque). In most
      indoor environments with no contamination from cigarette smoke the AA levels were
      below 20 ng/m3, whereas in the presence of smokers higher values were observed.
      Aniline levels were more erratic (varying from 53 ng/m3 (office of non-smokers)
      to 1929 ng/m3 (discotheque) and were not related to cigarette smoke. The
      concentration range of AA (excluding aniline) in the outside air varied from 3
      ng/m3 (Siena) to 104 ng/m3 (Brindisi); aniline concentration was extremely
      variable. Most samples of outdoor air had AA levels lower than 40 ng/m3. In
      conclusion, AA are widespread air contaminants and attain a high concentration in
      heavily contaminated indoor environments, due to smoking and poor ventilation. AA
      occasionally attain a high level in outdoor air as well. Therefore, a strategy of
      reduction of the exposure to AA should consider the abatement of multiple sources
      of contamination.

PMID- 11302582
TI  - QSAR models for estimating properties of persistent organic pollutants required
      in evaluation of their environmental fate and risk.
AB  - The molecular connectivity indices (MCIs) have been successfully used for over 20
      years in quantitative structure activity relationships (QSAR) modelling in
      various areas of physics, chemistry, biology, drug design, and environmental
      sciences. With this review, we hope to assist present and future QSAR
      practitioners to apply MCIs more wisely and more critically. First, we have
      described the methods of calculation and systematics of MCIs. This section should
      be helpful in rational selection of MCIs for QSAR modelling. Then we have
      presented our long-term experience in the application of MCIs through several
      characteristic and successful QSAR models for estimating partitioning and
      chromatographic properties of persistent organic pollutants (POPs). We have also
      analysed the trends in calculated MCIs and discussed their physical
      interpretation. In conclusion, several practical recommendations and warnings,
      based on our research experience, have been given for the application of MCIs in
      the QSAR modelling.

PMID- 11302583
TI  - Fate, effects and potential environmental risks of ethylene glycol: a review.
AB  - The fate, effects, and potential environmental risks of ethylene glycol (EG) in
      the environment were examined. EG undergoes rapid biodegradation in aerobic and
      anaerobic environments (approximately 100% removal of EG within 24 h to 28 days).
      In air, EG reacts with photo-chemically produced hydroxyl radicals with a
      resulting atmospheric half-life of 2 days. Acute toxicity values (LC(50)s and
      EC(50)s) were generally >10,000 mg/l for fish and aquatic invertebrates. The data
      collectively show that EG is not persistent in air, surface water, soil, or
      groundwater, is practically non-toxic to aquatic organisms, and does not
      bioaccumulate in aquatic organisms. Potential long-term, quasi-steady state
      regional concentrations of EG estimated with a multi-media model for air, water,
      soil, and sediment were all less than predicted no effect concentrations (PNECs).

PMID- 11302584
TI  - Neural networks studies: quantitative structure-activity relationships of
      antifungal 1.
AB  - Models of relationships between structure and antifungal activity of 1-[2
      (substituted phenyl)allyl]imidazoles and related compounds were constructed by
      means of a multilayer neural network using the back-propagation (BP) algorithm.
      Each molecule was described by three structural and one physicochemical
      parameters. The leave-one-out procedure was used to assess the predictive ability
      of a neural network model. The results obtained were compared to those given in
      the literature by the multiple linear regression (MLR), and were found to be
      better. The contribution of each descriptor to the structure-activity
      relationships was evaluated. Hydrophobicity of the molecule was confirmed to take
      the most relevant part in the molecular description.

PMID- 11302585
TI  - A study of the regional load deflection rate of multiloop edgewise arch wire.
AB  - To quantify the unique mechanical properties of multiloop edgewise arch wire
      (MEAW), its load deflection rate (LDR) and the LDR of various arch wires in the
      individual interbracket span were measured and compared. The MEAW arch wires were
      made out of .016 x .022-inch Permachrome stainless steel wire with L-loops of 4
      different sizes. Five samples of each size were prepared for the comparison
      against wires of plain stainless steel, TMA, and nickel-titanium (NiTi) wires,
      all of the same dimensions. Five specimens for each of the various wires were
      used to eliminate the possibility of change in the physical properties of wires
      caused by the stress from repeated measurement. The LDR was measured by using the
      Instron model 4466 at a crosshead speed of 1 mm/min and maximum deflection of 1.0
      mm. The regional wire stiffness of MEAW was calculated from the LDR in the
      interbracket spans that were measured by the Instron. The findings were as
      follows: (1) The LDR of the L-loop of MEAW at an individual interbracket span
      rate was 1:7.54 of the plain stainless steel wire, 1:1.76 of the NiTi, and 1:2.72
      of TMA. (2) The L-loop at an individual interbracket span showed much lower wire
      stiffness than the entire arch wire, and the value of the stiffness differed
      according to the region.

PMID- 11302586
TI  - The effects of overbite on the maxillary and mandibular morphology.
AB  - The aim of this study was to investigate the differences in the maxillary and
      mandibular morphology related to the overbite. A total of 80 untreated subjects
      were divided into 4 groups with normal overbite, edge-to-edge bite, open bite, or
      deep bite and were compared with one another. Differences between the overbite
      groups and between genders were assessed by means of variance analysis and the
      least significant difference test. In addition, correlation coefficients between
      the overbite and other variables were calculated. The results showed that there
      are statistically significant differences in the maxillary and mandibular
      morphology among the overbite groups.

PMID- 11302587
TI  - Sucking, chewing, and feeding habits and the development of crossbite: a
      longitudinal study of girls from birth to 3 years of age.
AB  - The prevalence of posterior crossbite among pacifier-sucking girls in Falkoping,
      Sweden, was previously found to be 26%. The aim of this investigation was to
      follow the development of crossbites in pacifier suckers and to determinate the
      possibility of reducing the prevalence of crossbite by informing and instructing
      the parents about sucking habits and reducing the time the child has the pacifier
      in the mouth. Parents of 60 consecutively born girls belonging to St Olof's
      health district, Falkoping, Sweden, were invited to take part in the study. All
      parents agreed to participate. Five interviews or examinations of each girl took
      place from birth until 3 years of age. Fifty-four (90%) of the 60 girls were
      breast-fed. The mean duration of breast-feeding was 8 months, and 67% of the
      girls were breast-fed for half a year or more. Forty-three children (72%)
      developed a pacifier-sucking habit, 6 (10%), a digit-sucking habit, and 11 (18%),
      no sucking habits. The mean duration of breast-feeding was longer for the
      nonsuckers (11 months) than for the pacifier- and digit-sucking children (5
      months). Of the 39 girls who still had the pacifier habit at 3 years of age, 2
      had developed a posterior crossbite. Another girl stopped the habit when a
      crossbite was registered at the 2 1/2-year examination. At the next appointment,
      the crossbite had corrected itself spontaneously. One of the 2 girls with
      crossbite at 3 years of age developed a prenormal occlusion with both anterior
      and posterior crossbites. For 12 more pacifier suckers, an interfering contact
      was noted with a forced guidance of the mandible and a midline shift. In all 12
      cases, the interfering teeth were primary canines. We conclude that parents
      should be instructed to reduce the "in the mouth time" of the pacifier. The
      transverse occlusal relationship in pacifier-sucking children should be evaluated
      between 2 and 3 years of age. If interfering contacts of the primary canines
      exist, the parents should be instructed to reduce the pacifier-sucking time.

PMID- 11302588
TI  - Effects of early activator treatment in patients with class II malocclusion
      evaluated by thin-plate spline analysis.
AB  - The aim of the present longitudinal cephalometric study was to evaluate the
      dentofacial shape changes induced by activator treatment between 9.5 and 11.5
      years in male Class II patients. For a rigorous morphometric analysis, a thin
      plate spline analysis was performed to assess and visualize dental and skeletal
      craniofacial changes. Twenty male patients with a skeletal Class II
      malrelationship and increased overjet who had been treated at the University of
      Heidelberg with a modified Andresen-Haupl-type activator were compared with a
      control group of 15 untreated male subjects of the Belfast Growth Study. The
      shape changes for each group were visualized on thin-plate splines with one
      spline comprising all 13 landmarks to show all the craniofacial shape changes,
      including skeletal and dento-alveolar reactions, and a second spline based on 7
      landmarks to visualize only the skeletal changes. In the activator group, the
      grid deformation of the total spline pointed to a strong activator-induced
      reduction of the overjet that was caused both by a tipping of the incisors and by
      a moderation of sagittal discrepancies, particularly a slight advancement of the
      mandible. In contrast with this, in the control group, only slight localized
      shape changes could be detected. Both in the 7- and 13-landmark configurations,
      the shape changes between the groups differed significantly at P < .001. In the
      present study, the morphometric approach of thin-plate spline analysis turned out
      to be a useful morphometric supplement to conventional cephalometrics because the
      complex patterns of shape change could be suggestively visualized.

PMID- 11302589
TI  - A finite element model of apical force distribution from orthodontic tooth
      movement.
AB  - This study was undertaken to determine the types of orthodontic forces that cause
      high stress at the root apex. A 3-dimensional finite element model of a maxillary
      central incisor, its periodontal ligament (PDL), and alveolar bone was
      constructed on the basis of average anatomic morphology. The maxillary central
      incisor was chosen for study because it is one of the teeth at greatest risk for
      apical root resorption. The material properties of enamel, dentin, PDL, and bone
      and 5 different load systems (tipping, intrusion, extrusion, bodily movement, and
      rotational force) were tested. The finite element analysis showed that purely
      intrusive, extrusive, and rotational forces had stresses concentrated at the apex
      of the root. The principal stress from a tipping force was located at the
      alveolar crest. For bodily movement, stress was distributed throughout the PDL;
      however, it was concentrated more at the alveolar crest. We conclude that
      intrusive, extrusive, and rotational forces produce more stress at the apex.
      Bodily movement and tipping forces concentrate forces at the alveolar crest, not
      at the apex.

PMID- 11302590
TI  - Three dimensional analysis of facial movement in normal adults: influence of sex
      and facial shape.
AB  - The aim of this study was to quantify facial movements in a sample of normal
      adults and to investigate the influence of sex and facial shape on these
      movements. The study sample consisted of 50 healthy adult subjects, 25 males and
      25 females (age: mean = 27.3 years; range = 23-39 years). A video-based tracking
      system was used to track small-diameter retroreflective markers positioned at
      specific facial sites. Subjects were instructed to make 7 maximum facial
      animations from rest, and the facial movements for each animation were
      characterized as the vectors of maximum displacement. Hotelling's T2 was used to
      test for significant sex differences in facial movements. In order to determine
      the effects of facial shape on facial movements, an index of facial shape was
      first calculated for each subject, and then a mixed-model ANOVA was used with
      facial shape (index), sex, and the interaction between facial shape and sex as
      fixed effects and subject as a random effect. The results demonstrated specific
      movement patterns for each animation. In general, males had larger movements than
      females and facial shape had a small but significant effect on facial movements.
      By comparing patient movements with the data from this large normative sample,
      the utility of this method to assess region-specific movement deficits was
      demonstrated.

PMID- 11302591
TI  - Orthodontic in vivo bond strength: comparison with in vitro results.
AB  - The purpose of the present study was to test a new in vivo debonding device and
      compare in vivo bond strengths recorded by this device with in vitro bond
      strengths recorded by a universal testing machine such as the Instron. For the in
      vitro part of the study, 60 extracted premolar teeth were divided into 2 groups
      of 30 each. Both groups of 30 teeth had 3M Unitek Victory Twin brackets,
      precoated with Transbond XT composite resin, bonded to them. Shear bond strength
      tests were carried out in vitro using the universal testing machine on one group
      of 30 teeth while the debonding device was used on the other group of 30 teeth.
      The mean shear bond strength of the group debonded using the universal machine
      was 11.02 MPa and that of the group debonded with the debonding device was 12.82
      MPa. For the in vivo part of the study, 8 patients randomly assigned to the
      research clinician from patients in The University of Alabama School of
      Dentistry, Department of Orthodontics, had a total of 60 premolar teeth bonded
      with 3M Unitek Victory Twin brackets. Following comprehensive orthodontic
      treatment (average time of 23 months), shear bond strength tests were carried out
      using the debonding device, which can measure debonding forces in vivo. The mean
      shear bond strength recorded in vivo was 5.47 MPa. Statistically significant
      differences were found between all 3 groups tested. The results appear to
      indicate that mean bond strengths recorded in vivo following comprehensive
      orthodontic treatment are significantly lower than bond strengths recorded in
      vitro.

PMID- 11302592
TI  - An evaluation of the quality of orthodontic attachment offered by single- and
      double-mesh bracket bases using the finite element method of stress analysis.
AB  - The objective of this study was to evaluate the influence of bracket base mesh
      geometry on the stresses generated in the bracket-cement-tooth continuum by a
      shear/peel load case. A validated three-dimensional finite element model of the
      bracket-cement-tooth system was constructed consisting of 15,324 nodes and 2971
      finite elements. Cement geometric and physical properties were held constant and
      bracket base geometry was varied, representing a variety of single-mesh
      configurations and 1 double-mesh design. For the single-mesh designs, increasing
      wire diameter (100-400 microm) resulted in a decrease in enamel and cement
      stresses. Increases in wire mesh spacing (200-750 microm) increased the major
      principal stress recorded in the enamel and adhesive at all wire diameters.
      Within the bracket, the major principal stress increased significantly at wire
      spacing above 400-500 microm. However, within the impregnated wire mesh (IWM),
      the major principal stress decreased as wire space increased. When the double
      mesh bracket base was considered, the combined mesh layers resulted in a decrease
      in the stresses recorded in the most superficial (coarse) mesh layer and an
      increase in the stresses recorded in the deepest (fine mesh) layer when compared
      with the single-layer designs in isolation. Modification of single-mesh spacing
      and wire diameter influences the magnitude and distribution of stresses within
      the bracket-cement-tooth continuum. The use of a double-mesh design results in a
      reduction in the stresses recorded in the most superficial mesh. Mesh design
      influenced stress distribution in this study, primarily by determining the
      flexibility of the bracket base.

PMID- 11302593
TI  - Thin-plate spline analysis of mandibular growth.
AB  - The analysis of mandibular growth changes around the pubertal spurt in humans has
      several important implications for the diagnosis and orthopedic correction of
      skeletal disharmonies. The purpose of this study was to evaluate mandibular shape
      and size growth changes around the pubertal spurt in a longitudinal sample of
      subjects with normal occlusion by means of an appropriate morphometric technique
      (thin-plate spline analysis). Ten mandibular landmarks were identified on lateral
      cephalograms of 29 subjects at 6 different developmental phases. The 6 phases
      corresponded to 6 different maturational stages in cervical vertebrae during
      accelerative and decelerative phases of the pubertal growth curve of the
      mandible. Differences in shape between average mandibular configurations at the 6
      developmental stages were visualized by means of thin-plate spline analysis and
      subjected to permutation test. Centroid size was used as the measure of the
      geometric size of each mandibular specimen. Differences in size at the 6
      developmental phases were tested statistically. The results of graphical analysis
      indicated a statistically significant change in mandibular shape only for the
      growth interval from stage 3 to stage 4 in cervical vertebral maturation.
      Significant increases in centroid size were found at all developmental phases,
      with evidence of a prepubertal minimum and of a pubertal maximum. The existence
      of a pubertal peak in human mandibular growth, therefore, is confirmed by thin
      plate spline analysis. Significant morphological changes in the mandible during
      the growth interval from stage 3 to stage 4 in cervical vertebral maturation may
      be described as an upward-forward direction of condylar growth determining an
      overall "shrinkage" of the mandibular configuration along the measurement of
      total mandibular length. This biological mechanism is particularly efficient in
      compensating for major increments in mandibular size at the adolescent spurt.

PMID- 11302594
TI  - An occlusal and cephalometric analysis of maxillary first and second premolar
      extraction effects.
AB  - The purpose of this study was to examine dimensional changes in the maxillary
      arch following the extractions of maxillary first or second premolars. Pre- and
      posttreatment records of 71 patients treated by one experienced orthodontist were
      randomly selected from completed premolar extraction cases. Forty-five patients
      involved the extraction of maxillary first premolars; of these, 15 also had
      extractions of mandibular first premolars and 30 had extractions of mandibular
      second premolars. Twenty-six patients involved the extraction of maxillary second
      premolars, and all of these also had extractions of mandibular second premolars.
      Pretreatment factors that seemed to suggest a basis for the extraction choice in
      this sample included incisal overjet, molar relationship, and maxillary incisor
      protrusion. Mean reductions with treatment in the anteroposterior arch dimension
      were similar within all premolar extraction groups. There was evidence of greater
      mean maxillary intermolar-width reduction following the extractions of maxillary
      second premolars than following extractions of maxillary first premolars. Greater
      mean maxillary incisor retraction was found in the maxillary first premolar
      extraction group than in the maxillary second premolar group. A wide range of
      individual variation in incisor and molar changes did, however, accompany
      treatment involving both maxillary premolar extraction sequences.

PMID- 11302595
TI  - Standards of care--another perspective.

PMID- 11302596
TI  - Chest radiographic appearances in severely burned adults. A comparison of early
      radiographic and extravascular lung thermal volume changes.
AB  - Chest radiographs (CXRs) have previously been used as a diagnostic tool to detect
      changes in lung water. In this study CXR changes in severely burned adults, in
      the absence of an inhalation injury, preceded detectable increases in
      extravascular lung thermal volume (ELTV) by 3 to 5 days. The hypothesis that
      early CXR density changes in burned patients have an infectious cause, not
      related to changes in ELTV, was tested. Blood cultures, CXRs, and ELTV were
      evaluated during the first 15 days after injury in severely burned adults who had
      no identified inhalation injury. Chest radiographs were scored daily on a 1 to 5
      scale, with 1 = normal, 2 = peribronchial cuffing, 3 = mild interstitial
      infiltrates, 4 = severe interstitial infiltrates, and 5 = alveolar infiltrates.
      In all patients, except those who were septic, increases in their CXR density
      scores correlated well with increases in ELTV. The ELTV/CXR score ratios for
      septic burn patients on days 1 to 6 postburn was 1.7 +/- 0.2 compared with 4.2 +/
      0.4, (means +/- SEM) for nonseptic (P < .001), whereas the ELTV/CXR score ratios
      for septic and nonseptic patients, 7 to 15 days postburn, were 3.8 +/- 0.4 and
      3.4 +/- 0.5, respectively. We suggest that before any measurable change in ELTV
      early increases in CXR density scores in burned patients without a concomitant
      inhalation injury are caused by intraalveolar pneumonitis or hyaline membrane
      atelectasis and not increased ELTV.

PMID- 11302597
TI  - Reduced blood loss during burn surgery.
AB  - The purpose of this study was to investigate the use of subcutaneous injection of
      burn wounds and skin graft donor sites with an adrenaline-saline solution to
      reduce blood loss during burn surgery. This retrospective study reviewed the
      requirements of blood products in 30 randomly selected adult patients with more
      than 10% body area burned, who had at least one burn operation at a university
      regional burn center, between January 1991 and June 1997. Patients were matched
      by age and percent body area burned and stratified according to the surgical
      technique in two groups. In Group 1, 15 patients received the modified tumescent
      surgical technique: subcutaneous injection of adrenaline (1 part/million in warm
      saline solution) into the subcutaneous tissue of the donor sites for autologous
      skin graft and areas of burn eschar to be excised, combined with pneumatic
      tourniquets in extremities and saline-adrenaline soaked nonadherent pads. In
      Group 2, 15 patients received the traditional surgical technique: soaked gauze
      compresses with an adrenaline-thrombin solution (1 ml of 1:1,000 adrenaline,
      thrombin 10,000 units, and 1 L of normal saline). Outcome measures, transfusion
      of blood products, operating time and complications between the two patient
      groups were analyzed using the Wilcoxon 2-sample test. The two patient groups
      were not different by age (40.4 +/- 19.4 vs 38.9 +/- 17.9), percent total body
      area burned (27.6 +/- 15.4 vs 32.8 +/- 13.4), or percent full thickness burn (7.0
      +/- 8.5 vs 11.5 +/- 8.5). The modified tumescent surgical technique significantly
      reduced mean total blood units transfused per patient (7.9 +/- 11.5 vs 15.7 +/-
      12.9 units; P = .031), and the mean blood units transfused intraoperatively per
      patient (4.7 +/- 7.8 vs 8.9 +/- 8.0 units; P = .026). The modified tumescent
      surgical technique significantly reduced the intraoperative and total blood
      transfusion requirements in our thermally injured patients.

PMID- 11302598
TI  - Morphine-Infused silver sulfadiazine (MISS) cream for burn analgesia: a pilot
      study.
AB  - Pain is considered the most distressing symptom of a burn wound, with analgesia
      usually provided via oral or parenteral medications. Use of systemic opioids can
      be complicated by fluctuations in bioavailability, absorption, and clearance of
      drugs caused by the burn. There has been little research done in the area of
      topical medications for burn analgesia. The following is a double-blind, placebo
      controlled pilot study assessing the safety (side effects) and efficacy (pain
      ratings and medications administered) of morphine-infused silver sulfadiazine
      cream for burn pain. Four patients are reported on (2 in each group). Only
      participants taking placebo reported side effects related to morphine and
      necessitated anxiolytic medications. Pain ratings in the treatment group ranged
      from 0 to 7 with a mean of 2.1, whereas the placebo group's ratings ranged from 2
      to 8 with a mean of 5.6. The placebo group averaged 55.3 mg oral morphine per
      half day, whereas the treatment group averaged 42.9 mg.

PMID- 11302599
TI  - Cadaver donor discards secondary to serology.
AB  - The use of cadaveric skin has made a major impact in the survival of patients
      experiencing major thermal injury. However, the availability of cadaveric skin is
      often limited by potentially pathogenic organisms. Very little data exists as to
      why cadaveric skin from donors who have been previously screened was discarded.
      From March 1994 to March 1996, 813 donors were referred to our tissue bank. All
      donors were reviewed for the cause of death, history and physical, and social
      history. One hundred fifty-three donors screened were discarded. Sixty-one donors
      of this group were discarded because of positive serologies. The following are
      the percentages of the specific positive serologies: hepatitis B core antibody,
      52.3%; hepatitis B surface antigen, 18.1%; hepatitis C virus antibody, 14.3%;
      human immunodeficiency virus antibody, 4.9%; human T lymphocyte virus antibody,
      4.9% and syphilis, 5.5%. Retrospectively, all donor screening questionnaires were
      reviewed for possible indicators in relation to positive serologic testing.
      Current screening methods, although excellent in social screening, still fail to
      identify a significant number of donors who may have positive serologies because
      of hepatitis, human immunodeficiency virus, human T lymphocyte virus, or
      syphilis. As the field of tissue banking continues to evolve, the focus will need
      to be directed toward better screening mechanisms in order to decrease our
      current discard rates after donors have been approved through the screening
      process.

PMID- 11302600
TI  - Potential risk factors for deep venous thrombosis in burn patients.
AB  - Risk factors and prophylaxis for prevention of deep venous thrombosis (DVT) and
      pulmonary embolism remain controversial in burn patients. From January 1996
      through June 1999, we reviewed all adult burn patients admitted to our burn
      center with the in-hospital diagnosis of DVT and assessed each affected patient
      for DVT risk factors. There were 8 symptomatic DVTs and 2 pulmonary embolisms
      detected in 327 adult burn patients (2.4% incidence). No DVT patient had the risk
      factors of morbid obesity, previous DVT, congestive heart failure, or neoplastic
      disease. One patient was older than 65 years. All of the DVTs occurred in veins
      draining a burned extremity. Seven of 8 patients had burn wound infections as
      complications. Burns on the extremity developing the DVT as well as the diagnosis
      of a burn wound infection were significant risk factors for DVT formation. These
      findings prompt us to consider routine screening for DVT in burn patients with
      these risk factors.

PMID- 11302601
TI  - Toxic epidermal necrolysis (TEN) in elderly patients.
AB  - Toxic epidermal necrolysis (TEN) is a severe exfoliative disease of the skin and
      mucous membranes that results in high mortality. As the elderly population
      increases, the number of elderly patients with TEN can also be expected to
      increase. Elderly patients with comparably sized burn wounds usually have a poor
      prognosis. Our purpose was to determine whether elderly TEN patients exhibit
      similarly high mortality. A retrospective review was conducted of 52 patients
      treated for TEN from October 1991 through September 1998. Eleven patients were
      older than 65 years. All patients were treated according to our TEN protocol.
      Eight of 11 patients recovered, and 3 died. The mean total body surface area
      (TBSA) involvement for the patients who recovered was 24%, compared with 66% for
      the nonsurvivors. The survival rate for elderly patients (73%) compares well with
      that for those younger than 65 years (89%). Therefore, we propose that we should
      be aggressive in treating elderly patients with TEN.

PMID- 11302602
TI  - Glucagon-like peptide-2 stimulates gut mucosal growth and immune response in
      burned rats.
AB  - Major burn trauma often leads to reduced gut barrier function, immunosuppression,
      and increased bacterial translocation. We hypothesized that treatments that
      maintain normal gut after burn trauma will also reduce immunosuppression and
      bacterial translocation. Recent studies suggest that treatment with glucagon-like
      peptide-2 (GLP-2), which is synthesized in the intestine and released after food
      intake, elicits mucosal hyperplasia in the small intestine of rodents and
      prevents parenteral nutrition-induced gut hypoplasia. Therefore, we determined
      whether GLP-2 would prevent loss of gut integrity after major burn trauma.
      Osmotic minipumps were implanted into the peritoneum of 22 adult, male, Sprague
      Dawley rats to infuse saline (10 microl/hr; n = 14) or GLP-2 (1 microg/hr; n =
      8). On the next day 8 saline-infused and 8 GLP-2-infused rats were subjected to a
      25 sec duration 30% BSA open flame burn, with the remaining rats serving as sham
      burn controls. Five days after burn, all rats were killed. Gut protein was
      assessed, and immunosuppression was estimated by the mitogenic response of
      cultured splenocytes to phytohemagglutinin, pokeweed, and concanavalin A.
      Bacterial translocation was determined by culturing the mesenteric lymph nodes.
      Although protein content was significantly decreased in the ileum of burned rats
      treated with saline, the burned rats treated with GLP-2 exhibited significant
      increases in protein levels in duodenum, jejunum. and ileum. Colon protein was
      not affected by GLP-2 infusion. Saline-treated burned rats also exhibited
      immunosuppression, as suggested by significantly decreased responses to each of
      the mitogens. Infusion of GLP-2 normalized the response by the burned rats to
      each of the mitogens. Lymph nodes taken from sham rats exhibited no colony
      forming units, whereas in both of the burn groups, 50% of the cultures were
      positive. However, more aggressive colonization may have occurred in the saline
      infused burned rats as compared with the GLP-2-infused burned rats (81 +/- 63 vs
      3 +/- 2 colony forming units). These results suggest that GLP-2 may stimulate gut
      mucosa and reduce immunosuppression in burned rats. However, there does not seem
      to be a statistically significant positive effect of GLP-2 on bacterial
      translocation. Thus, improving small intestine mucosa may increase immunity while
      being ineffective against bacterial translocation.

PMID- 11302603
TI  - Burn patients' pain and anxiety experiences.
AB  - The purpose of this study was to examine burn patients' pain and anxiety
      experiences during resting conditions and procedures. The relationship of
      contextual factors and interventions to pain and anxiety were also explored.
      Procedural pain was significantly higher than resting pain (P = .02); however,
      there were no significant differences in anxiety between resting conditions and
      procedures (P = .16). There was a significant difference between burn patients'
      acceptable level of pain, resting pain, and procedural pain (P = .01). Resting
      pain was significantly lower than patients' acceptable level of pain (P = < .01).
      Procedural pain was slightly lower than patients' acceptable level of pain, but
      these results were not statistically significant (P = .37). Percent of total body
      surface burned was associated with increased procedural anxiety (P = .022).
      Family presence correlated with decreased procedural pain (P = .011) and
      midazolam use (P = .047). Prior experience with the procedure was associated with
      increased morphine(P = .003) and midazolam use (P = .029). These findings support
      the multifactorial nature of burn pain and anxiety and provide guidance for
      practice.

PMID- 11302604
TI  - Management of background pain and anxiety in critically burned children requiring
      protracted mechanical ventilation.
AB  - Optimal control of pain and anxiety is an elusive but important goal in children
      with protracted critical illness. This review represents an effort to document
      the doses of background medication required to achieve this goal in a group of
      children managed under a pain and anxiety protocol that adjusts background
      infusions to comfort. The course of children with wounds involving at least 10%
      of the body surface and coincident respiratory failure requiring mechanical
      ventilation for more than 7 days managed 1 Jan 97 to 31 Dec 98 was reviewed. A
      pain and anxiety protocol was used, including background infusions of morphine
      and midazolam adjusted to comfort. These 28 children had a mean (+/- standard
      deviation) age of 5.3 +/- 4.6 years, wound size of 48.3 +/- 28.4%, and were
      intubated for 25.0 +/- 23.9 days. Neuromuscular blocking drugs were administered
      for 65 of 447 (14.5%) ventilator days. To maintain comfort, drugs were required
      at doses substantially above standard dosing schemes. The highest daily
      background infusion of morphine sulfate averaged 0.40 mg/kg/hr +/- 0.24 mg/kg/hr
      (usual starting dose was 0.05 to 0.1 mg/kg/hr) and was reached 14.1 +/- 12.8 days
      after admission. The highest daily background infusion of midazolam averaged 0.15
      +/- 0.07 mg/kg/hr (usual starting dose was 0.04 mg/kg/hr) and was reached 14.0 +/
      3.8 days after admission. Morphine infusions at extubation averaged 0.22 +/-
      0.17 mg/kg/hr and midazolam infusions 0.10 +/- 0.12 mg/kg/hr. All children
      survived to discharge and there was no perceived morbidity related to these high
      doses of medication. Children with serious burns and respiratory failure will
      require high doses of background opiates and benzodiazepines to remain
      comfortable, because they develop drug tolerance during protracted critical
      illness. Infusions can be continued at a reduced dose through extubation, do not
      result in addiction or other apparent morbidity if adjusted to desired level of
      comfort, and may contribute to a reduced incidence of treatment-related stress
      disorders.

PMID- 11302605
TI  - Development, reliability, and concurrent validity of the modified inventory of
      potential reconstructive needs.
AB  - Documentation of burn sequelae can be a difficult and time-consuming task. To
      date a reliable and systematic format for recording postburn trauma is lacking.
      The purpose of this research was two-fold: first, to develop a Modified Inventory
      of Potential Reconstructive Needs from the original Inventory of Potential
      Reconstructive Needs to allow methodical documentation of functional and cosmetic
      burn sequelae in all body surface areas of children with burns and, second, to
      establish interrater reliability and concurrent validity of the instrument, thus
      allowing its clinical application. Two raters scored the Modified Inventory of
      Potential Reconstructive Needs on 41 children with a range of burns types and
      severity. Excellent interrater reliability was demonstrated for both total
      (intraclass correlation coefficient = 0.996) and subsection inventory scores.
      Concurrent validity was also established with total scores showing strong
      positive correlations (0.73-0.76) with three indicators of burn severity. These
      findings provide initial support for the tool's clinical applicability,
      particularly in relation to rehabilitative planning and documentation.

PMID- 11302606
TI  - The impact of protective hoods and their water content on the prevention of head
      burns in New York City firefighters: laboratory tests and field results.
AB  - The New York City Fire Department (FDNY) is the largest fire department in the
      United States. In 1996, FDNY added the thermal protective hood to its modern
      protective uniform. The purpose of this study is to determine 1) the
      effectiveness of hoods in reducing head burns and 2) whether hood water content
      (dry, damp, or saturated) affects the level of thermal protection. Laboratory
      tests (radiant heat performance, thermal protective performance, and fully
      dressed manikin) and FDNY field results were used. Laboratory tests evaluated 4
      different conditions (no hood, dry, damp, and saturated hoods) exposed to 4
      different heat fluxes (0.1, 0.25, 0.5, and 2.0 cal/cm2/sec) equivalent to
      approximate air temperatures of 200, 400, 600, and 2,250 degrees F. Field results
      compared FDNY head burns during 3 winters wearing the hood to 3 winters without
      hood. Wearing a hood dramatically reduced head burns. This was true for all
      laboratory tests, at all heat flux exposures, and all hood water content
      conditions. At 0.1 cal/cm2/sec, dry hoods were superior to wet hoods. At all
      other heat flux exposures, thermal protection was either not significantly
      different between water content conditions or improved as water content
      increased. Confirming these laboratory tests, FDNY field results showed
      significant decreases in neck burns (by 54%), ear burns (by 60%), and head burn
      totals (by 46%). Based on combined laboratory and field results, we strongly
      recommend the use of modern thermal protective hoods.

PMID- 11302607
TI  - Thermal injury and child abuse: the medical evidence dilemma.
AB  - The defense of the innocent, as well as the prosecution of the guilty, is a basic
      premise of American justice. This article reviews nine cases defended by the
      public defender system, in which the authors were involved, that illustrate some
      of the pitfalls in making the diagnosis of child abuse and/or neglect caused by
      thermal injury. The basis for the defense is also discussed, together with the
      biologic, engineering, and socioeconomic factors. The definition of child abuse
      and/or neglect is discussed, as is the devastating and long-lasting label of a
      false accusation, much less false imprisonment. In this regard this review
      concludes that professionals with thermal injury expertise must become involved
      in the judicial process if justice is to prevail.

PMID- 11302608
TI  - Hyperphosphatemia in a burn patient.
AB  - Hypophosphatemia has been observed in severely burned patients and has been
      associated with increased mortality. Hyperphosphatemia has rarely been described
      in this population. We present a burn patient with hyperphosphatemia,
      hypercalciuria, and suppressed parathyroid hormone level 5 months after the
      initial burn. The patient's presentation is most consistent with the effect of
      immobilization on bone and calcium metabolism.

PMID- 11302609
TI  - Childrens' distress during burn treatment is reduced by massage therapy.
AB  - Before dressing changes, 24 young children (mean age = 2.5 years) hospitalized
      for severe burns received standard dressing care or massage therapy in addition
      to standard dressing care. The massage therapy was conducted to body parts that
      were not burned. During the dressing change, the children who received massage
      therapy showed minimal distress behaviors and no increase in movement other than
      torso movement. In contrast, the children who did not receive massage therapy
      responded to the dressing change procedure with increased facial grimacing, torso
      movement, crying, leg movement and reaching out. Nurses also reported greater
      ease in completing the dressing change procedure for the children in the massage
      therapy group. These findings suggest that massage therapy attenuates young
      childrens' distress responses to aversive medical procedures and facilitates
      dressing changes.

PMID- 11302610
TI  - Assessment of skin pliability.

PMID- 11302611
TI  - Integra and cultured epithelium.

PMID- 11302612
TI  - Citation of Pandya et al.

PMID- 11302613
TI  - A multicenter clinical trial to evaluate the topical hemostatic efficacy of
      fibrin sealant in burn patients.
AB  - Current surgical management of deep partial-thickness and full-thickness burn
      wounds involves early excision and grafting. Blood loss during these procedures
      can be profound, thus prompting the use of topical hemostatic agents to control
      and minimize hemorrhage during grafting. The primary endpoint of this multicenter
      trial was to evaluate the efficacy of fibrin sealant as a topical hemostatic
      agent during skin grafting. The secondary endpoint was to obtain data to support
      the existing safety profile of a human fibrin sealant (FS) in participating
      patients as indicated by the type, severity, and frequency of any adverse events
      within the 24-hour postoperative period. A multicenter prospective, open label,
      Phase III multicenter, randomized, comparative clinical trial evaluated the use
      of fibrin sealant in burn patients undergoing skin graft procedures. Each patient
      served as his or her own control in this randomized, unblinded study of the
      effect on time to hemostasis in donor sites treated with the investigational FS
      product. At operation, 1 contiguous donor skin harvest site was bisected into 2
      equal halves, 1 of which was then randomly selected and treated with fibrin
      sealant. At the end of the fibrin sealant application, the time to hemostasis in
      each of the donor site halves was identified by the operating surgeon and
      recorded by the research coordinator. The use of any other topical hemostatic
      agents was prohibited. A significant difference (P < .001) was demonstrated in
      the mean time to hemostasis between the fibrin sealant treated donor sites when
      compared painwise to the control sites. The significant difference was consistent
      across the 6 participating study centers. There were no adverse events associated
      with the use of fibrin sealant. The investigational FS product was shown to be
      efficacious, because it significantly decreases the time to hemostasis at the
      donor skin harvest site in patients undergoing skin grafting and was noted not to
      cause any adverse reactions.

PMID- 11302615
TI  - Euzetia occultum n. g., n. sp. (Euzetiinae n. subf.), a monocotylid monogenean
      from the gills of Rhinoptera neglecta (Rhinopteridae) from Moreton Bay,
      Queensland, Australia.
AB  - Euzetia occultum n. g., n. sp. (Monogenea: Monocotylidae) is described from the
      gills of the Australian cownose ray Rhinoptera neglecta Ogilby collected in
      Moreton Bay, Queensland, Australia. Euzetia has one central and ten peripheral
      loculi, which is similar to species in Decacotyle Young, 1967. However Euzetia is
      distinguished from other genera in the family by the presence of an additional
      loculus on either side of the central loculus. Because Euzetia does not fit into
      any of the six existing subfamilies in the Monocotylidae Taschenberg, 1879, as
      currently recognised, we propose the Euzetiinae n. subf. to accommodate the new
      genus. Euzetia occaltum is described and illustrated fully. This is the first
      published record of a monocotylid from a species of Rhinoptera Cuvier.

PMID- 11302614
TI  - Two new species of Litobothrium Dailey, 1969 (Cestoda: Litobothriidea) from
      thresher sharks in the Gulf of California, Mexico, with redescriptions of two
      species in the genus.
AB  - As part of a survey of the metazoan parasites of elasmobranchs of the Gulf of
      California, Mexico, the spiral intestines of 10 pelagic thresher sharks Alopias
      pelagicus and one bigeye thresher shark A. superciliosus were examined for
      tapeworms. Eight of the A. pelagicus specimens examined were found to host
      Litobothrium amplifica and L. daileyi. Both tapeworm species are redescribed
      based on examination of this new material with light and scanning electron
      microscopy, and the ranges of most of the measurements for these species are
      expanded; scanning electron micrographs and detailed illustrations and
      measurements of their segment anatomy are presented for the first time. An
      argument is made that the identification of the original host specimens of these
      species was in error and that A. pelagicus is likely to be the correct original
      host. In addition, L. nickoli n. sp., a third species in the genus hosted by A.
      pelagicus, was found in three of the 10 individual hosts examined. This species
      differs from all six known Litobothrium species in the form of the pseudosegments
      of the scolex, the anterior two being essentially non-cruciform, while the latter
      three are distinctly cruciform. All other species possess either no non-cruciform
      or at most one non-cruciform segment anteriorly. The single specimen of A.
      superciliosus examined was found to host the new species, L. janovyi. This
      species differs from L. coniformis, L. gracile and L. amsichensis in its
      possession of four rather than three, three and five cruciform pseudosegments,
      respectively. It lacks the modificiations of the fourth pseudosegment seen in L.
      amplifica and lacks the anterior non-cruciform fifth pseudosegment found in L.
      daileyi. It most closely resembles L. alopias but differs among other features in
      its greater total length, greater number of segments and longer mature segments.
      SEM of the four species collected from the Gulf of California as well as material
      of L. amsichensis from the goblin shark Mitsukurina owstoni that hosted the type
      specimens of this species show that all surfaces of the body of all five species
      bear a dense covering of long filiform microtriches. L. amplifica bears a single
      row of large spine-like structures throughout most of the posterior margins of
      the first and second cruciform pseudosegment only. L. daileyi possesses one to
      two rows of overlapping spine-like structures on the posterior margins of the
      first four pseudosegments with the exception of the medial projections. The fifth
      pseudosegment lacks these structures. L. janovyi n. sp. bears spine-like
      structures on the lateral margins of only the third and fourth pseudosegments. L.
      nickoli n. sp. bears spine-like structures throughout the posterior margins of
      the first and second pseudosegments, and throughout the posterior margins of the
      third and fourth pseudosegments with the exception of the medial projections; the
      fifth pseudosegment lacks these structures. L. amsichensis bears no structures
      that could be considered to be spine-like on any of its pseuosegments, but
      possesses a border of densely arranged larger microtriches on the posterior
      margin of all five pseudosegments. A key to the species is included.

PMID- 11302616
TI  - The New World filarial genus Molinema Freitas & Lent, 1939 (Nematoda:
      Onchocercidae), with a description of four new species parasitic in the
      Echimyidae (Rodentia).
AB  - Four new species of Molinema (Filarioidea: Onchocercidae), parasites of echimyid
      rodents in South America, are described: M. algardneri n. sp. from Proechimys
      amphichoricus, M. barbarae n. sp. from P. cayennensis, both in Venezuela (Rio
      Negro and Cerro La Neblina, respectively), M. peruviensis n. sp. from P. steerei
      in Peru (lower Urubamba), and M. nattereri n. sp. (= Filaria diacantha Molin,
      1858 pro parte) from Echimys ? didelphoides (= Loncheres rufa) in Brazil (Matto
      Grosso). They differ from each other and from the previously described species in
      the following characters: flat or concave head, cephalic ratio (distance between
      cephalic papillae in median view/lateral view), size and shape of the buccal
      capsule, length of the oesophagus, cuticular ornamentation of the female body,
      length of the ovijector, thick or slim female tail, area rugosa, long or short
      filament in the left spicule, heel in the right spicule, respective position of
      postcloacal papilla pairs 5 and 6, shape of the caudal lappets, terminal point
      present or absent, and the microfilariae. Molinema, which belongs to the
      worldwide Dipetalonema line, is distributed in two of the ten families of the
      Caviomorpha (South American Hystrichognathi have extended their distribution in
      South America since the early Oligocene). Nine species are parasitic in the
      Echimyidae (suborder Caviida); they have a short oesophagus and a complete or
      reduced set of precloacal papillae (four or three pairs). Two species are
      parasitic in the Erethizontidae (Erethizontida) and might be more primitive in
      having a well-developed oesophagus. However, the type-species M. diacantha, of
      which a female specimen was studied, has a large buccal capsule and has evolved
      concave head, while M. arbuta has a reduced buccal capsule and primitive flat
      head. This last species is a parasite of a Nearctic porcupine and probably
      represents a small line of Molinema which migrated to the north with its hosts
      when communications were established between the two American continents 3 mya
      (Pleistocene). M. sprenti, the unique parasite of the Castoridae in North
      America, is considered to be derived from this group by capture.

PMID- 11302617
TI  - Proemotobothrium n. g. (Cestoda: Trypanorhyncha), with the redescription of P.
      linstowi (Southwell, 1912) n. comb. and description of P. southwelli n. sp.
AB  - A new genus, Proemotobothrium (Trypanorhyncha: Otobothriidae), is erected to
      contain P. linstowi (Southwell, 1912) n. comb. (syn. Otobothrium magnum
      Southwell, 1924) and P. southwelli n. sp. The new genus is characterised by two
      bothridia, paired bothridial pits, an acraspedote scolex, elongate bulbs, four
      hooks per principal row, hooks 4 (4') being small and uncinate, a single,
      filiform, intercalary hook between each principal row and by the arrangement, in
      tandem, of the two or three extra hooks of the armature of the external surface
      of the tentacle, a pattern previously known only in the family Mixodigmatidae.
      The two species are distinguished from one another on the basis of measurements
      of the scolex and bulbs, the sizes of the hooks of the principal rows and by the
      number and size of the additional hooks in the linear arrays on the external
      surface of the tentacle.

PMID- 11302618
TI  - Can airway complications following multilevel anterior cervical surgery be
      avoided?
AB  - OBJECT: The authors conducted a study to determine how to avoid emergency
      postoperative reintubation and its associated morbidity in patients who have
      undergone multilevel anterior-posterior cervical spine surgery. METHODS: In a
      group effort between the departments of anesthesia and neurosurgery, a protocol
      was developed to avoid having to reintubate patients postoperatively. As a
      preventative measure, patients remained intubated overnight; on the 1st
      postoperative day or thereafter, based on direct fiberoptic visualization of
      reactive tracheal swelling, an anesthesiologist extubated the patients. Fifty
      eight patients underwent multilevel anterior corpectomy with fusion (ACF; with 41
      receiving plates and 17 not receiving plates), posterior wiring and fusion (PWF),
      and application of a halo. On average, ACF involved three levels, whereas PWF
      included 6.5 levels. Surgery typically lasted 10 hours, and an average 2.6 U of
      blood was required. Forty patients were successfully extubated on the 1st, five
      on the 2nd, three on the 3rd, two on the 4th, two on the 5th, and three on the
      7th postoperative day. Three elective tracheostomies were performed on the 7th
      postoperative day. Risk factors associated with delayed extubation or
      tracheostomy in 18 patients included: operative time longer than 10 hours (12
      patients), obesity greater than 220 lbs (12 patients), transfusion of more than 4
      U of blood (10 patients), ACF reoperations (nine patients), ACF including C-2
      (seven patients), four-level ACF (five patients), and asthma (five patients). In
      the only case in which emergency reintubation was required, three risk factors
      were present. CONCLUSIONS: Emergency reintubation following anterior-posterior
      cervical surgery and fusion can be avoided by maintaining intubation overnight
      and subsequently having an anesthesiologist remove the tube after healing is
      fiberoptically confirmed. Familiarity with major risk factors contributing to
      airway compromise, combined with this protocol, should minimize the significant
      morbidity associated with reintubation following multilevel anterior-posterior
      cervical fusion.

PMID- 11302619
TI  - Clinical and radiological correlates of severity and surgery-related outcome in
      cervical spondylosis.
AB  - OBJECT: The aim of this study was to determine if radiological features could be
      used to predict outcome in patients with cervical spondylotic myelopathy (CSM).
      METHODS: The authors studied 69 patients consecutively referred to The National
      Hospital, Queen Square, for decompressive surgery. Data obtained from
      preoperative cervical spine magnetic resonance (MR) imaging studies were each
      analyzed on two separate occasions by two blinded radiologists. The parameters
      determined were signal change and the presence and severity of compression.
      Clinical outcome was determined by pre- and postoperative timed walks, as well as
      by evaluation of myelopathy disability index scores, Ranawat classification, and
      Nurick grades. There was good inter- and intraobserver reliability for
      determination of radiological data. A significant relationship was found between
      MR imaging signal change and surgery-related outcome, as reflected by improvement
      in walking parameters; however, this was confounded by the fact that signal
      change also related to preoperative walking parameters, and those patients for
      whom preoperative walking function was worse experienced greater functional
      improvement in walking postoperatively. The relationships between ambulatory
      related data and severity or extent of spinal cord compression were less marked.
      CONCLUSIONS: Cervical cord compression and intrinsic MR imaging signal change
      correlate with clinical severity, and, in this population, the presence of signal
      change was correlated with better surgery-related outcome. However, confounding
      factors and the lack of strong correlation indicate that these radiological
      measurements are insufficient to be used as a reliable tool for predicting
      surgery-related benefits in individual patients.

PMID- 11302620
TI  - Surgical and endovascular treatment of spinal dural arteriovenous fistulas: long
      term disability assessment and prognostic factors.
AB  - OBJECT: The authors assessed clinical outcomes of patients with treated spinal
      dural arteriovenous fistulas (DAVFs) and investigated prognostic factors.
      METHODS: Thirty consecutive patients with spinal DAVFs were treated at the
      authors' institution during the past 15 years: seven underwent surgery; seven
      underwent surgery after failed embolization: and 16 underwent embolization alone.
      The outcomes of gait and micturition disability, were analyzed. Follow up
      averaged 3.4 years (range 1 month-11.8 years). Age, duration of symptoms, pre-
      and postintervention magnetic resonance (MR) imaging findings, and
      preintervention disability were correlated with outcome. Seventeen patients (57%)
      experienced improved gait, 12 (40%) were unchanged, and one (3%) was worse. In 11
      patients (37%) micturition function was improved, in 15 (50%) it was unchanged,
      and in four (13%) it was worse. Gait disability, as measured by the Aminoff-Logue
      Scale, was significantly improved after treatment, from 3.4+/-1.4 (average +/-
      standard deviation) to 2.7+/-1.5 (p = 0.007). Mean micturition disability scores
      decreased, but not significantly, from 1.9+/-1 to 1.6+/-1.1 (p = 0.20).
      Preintervention gait disability was not associated with improvement except for
      patients with Aminoff-Logue Scale Grade 4 disability (eight of nine improved; p =
      0.024). For patients treated within 13 months of symptom onset, mean micturition
      disability decreased (p = 0.035). No association was found between clinical
      improvement and age, a symptom duration less than 30 months, or pre- and
      postintervention MR imaging-documented spinal cord edema. CONCLUSIONS: Spinal
      DAVF treatment significantly improved patients' mean gait disability score by
      almost one grade at last follow up. The mean micturition disability score was not
      significantly improved, unless treatment was performed within 13 months of
      symptom onset. Longer and more uniform follow-up study is needed to determine if
      improved and stabilized clinical outcomes are sustained.

PMID- 11302621
TI  - Surgery in adults with tethered cord syndrome: outcome study with independent
      clinical review.
AB  - OBJECT: The authors conducted a study to evaluate the risks and short-term
      benefits of surgical treatment for tethered cord syndrome (TCS) in patients older
      than 18 years of age. METHODS: The authors studied a series of 57 consecutive
      adult patients with TCS of varying origins. Patients were examined by the same
      neurologist in a standardized fashion before and after surgery, and most were
      followed for at least 2 years postoperatively. Patient age ranged from 19 to 75
      years. The mean age at onset of symptoms and diagnosis was 30 years and 37 years,
      respectively. Muscle strength improved (15 cases) or showed no change
      postoperatively (38 cases) in a large majority of patients (93%). In four
      patients a minor decrease in muscle strength was demonstrated, and there was
      significant deterioration in two (3.5%). In the two latter patients, a rapid
      decline in motor function was present preoperatively. Subjective assessment of
      pain, gait, sensory function, and bladder/bowel function at 4 weeks, 6 months,
      and 2 years postsurgery revealed improvement in a substantial percentage of
      patients. No major surgery-related complications occurred. CONCLUSIONS: This is
      the largest series to date in which adult patients with TCS comprise the report.
      Untethering procedures in these patients were safe and effective, at least in the
      short term. Patients with rapid loss of motor function, lipomyelomeningocele, or
      split cord malformation seem to be at a higher risk of postsurgery deterioration.
      A follow-up period of many more years will be necessary to determine whether
      aggressive surgery is beneficial in the long term.

PMID- 11302622
TI  - Giant invasive spinal schwannomas: definition and surgical management.
AB  - OBJECT: Confusion exists regarding the term giant spinal schwannoma. There are a
      variety of nerve sheath tumors that, because of their size and extent, justify
      the label "giant schwannoma." The authors propose a classification system for
      spinal schwannomas as a means to define these giant lesions. The classification
      is confined to tumors that are essentially intraspinal, with or without
      extraspinal components. Lesions that erode the vertebral bodies (VBs) and extend
      posteriorly and laterally into the myofascial planes are classified as giant
      "invasive" spinal schwannomas. METHODS: The records of patients with giant
      invasive spinal schwannoma were analyzed. The radiological features, operative
      approaches, and intraoperative findings were noted. Ten patients with giant
      invasive tumors were surgically treated over the last 8 years. Six patients were
      male. Erosion of the posterior surface of the VBs was the diagnostic finding
      demonstrated on plain x-ray films. Magnetic resonance imaging delineated the
      extent of the tumors and helped in preoperative planning. Radical excision of the
      tumors in multiple stages was possible in eight of the 10 patients. Dural
      reconstruction was required in four patients. All patients required fusion, and
      an additional stabilization procedure was undertaken in three patients.
      CONCLUSIONS: The authors conclude that giant invasive schwannomas are uncommon
      lesions and propose a new classification system. Because of their locally
      "invasive" nature and extension in all directions, careful preoperative planning
      of the surgical approach is very important. Although radical excision is possible
      and promises good results, recurrences may occur and multiple surgical procedures
      may be required.

PMID- 11302623
TI  - Transforaminal percutaneous endoscopic discectomy in the treatment of far-lateral
      and foraminal lumbar disc herniations.
AB  - OBJECT: Far-lateral (extraforaminal) and foraminal disc herniations comprise up
      to 11% of all herniated intervertebral discs. Operative management can be
      technically difficult, and the optimum surgical treatment remains controversial.
      Accessing these lateral disc herniations endoscopically via a percutaneous
      transforaminal approach offers several theoretical advantages over the more
      traditional procedures. The object of this study was to assess the safety and
      efficacy of treating patients with far-lateral and foraminal disc herniations via
      a percutaneous transforaminal endoscopic approach. METHODS: A retrospective
      analysis was performed of 47 consecutive patients who underwent surgery via this
      approach. All procedures were performed after induction of a local anesthetic on
      an outpatient basis. Outcome was measured with Macnab criteria and by determining
      a patient's return-to-work status. The median follow-up period was 18 months
      (range 4-51 months). Excellent or good outcome was obtained in 40 (85%) of 47
      patients. Of the 38 patients working before the onset of symptoms, 34 (90%)
      returned to work. Five patients (11%) experienced poor outcomes and subsequently
      underwent open procedures at the same level. Of the 10 recipients of Workers'
      Compensation, Macnab criteria indicated a significantly worse outcome (70%
      excellent or good), but an excellent return-to-work status was maintained (90%).
      There were no complications. CONCLUSIONS: Transforaminal percutaneous endoscopic
      discectomy is safe and efficacious in the treatment of far-lateral and foraminal
      disc herniations.

PMID- 11302624
TI  - Clinical analysis and prognostic study of ossified ligamentum flavum of the
      thoracic spine.
AB  - OBJECT: A variety of factors may affect surgery-related outcome in patients with
      ossification of the ligamentum flavum (OLF) of the thoracic spine. The aim of
      this study was to determine these factors on the basis of preoperative clinical
      and radiological findings. METHODS: The authors treated 31 cases of symptomatic
      thoracic OLF between 1988 and 1999. The following factors were retrospectively
      studied: patient age, sex, morbidity level, initial symptoms, chief complaint,
      duration of symptoms, patellar reflex, Achilles reflex, computerized tomography
      (CT) finding, presence of intramedullary change determined by magnetic resonance
      imaging, coexistent spinal lesions, preoperative grade, and postoperative grade.
      A decompressive laminectomy was performed in all cases. In 29 patients (94%)
      improved symptoms were demonstrated postoperatively. In terms of functional
      prognosis, the preoperative duration of symptoms was significantly shorter in the
      group of patients with excellent outcomes than in those with fair outcomes (p <
      0.05). No significant difference was observed in the correlation between other
      factors. To evaluate the degree of preoperative thoracic stenosis and the
      severity/extent of OLF-induced spinal compression, we used an original OLF CT
      scoring system. A score of excellent on the CT scale tended to indicate an
      excellent prognosis (p < 0.01). CONCLUSIONS: Thoracic OLF frequently develops in
      the lower-thoracic spine in middle-aged men, and it is complicated by various
      spinal lesions in many cases. Early diagnosis and treatment are important for
      understanding the clinical symptoms and imaging diagnosis because the present
      findings suggest that a delay in diagnosis and treatment correlates with the
      functional prognosis postoperatively.

PMID- 11302625
TI  - Long-lasting analgesic effect of radiofrequency treatment of the lumbosacral
      dorsal root ganglion.
AB  - OBJECT: The authors conducted a study to establish the benefit of radiofrequency
      (RF) treatment of the lumbosacral dorsal root ganglion (DRG) as a therapy to
      reduce symptomatic pain in patients with chronic spinal pain radiating to the
      leg. METHODS: Two hundred seventy-nine patients were evaluated after undergoing
      their first RF treatment of the DRG. A four-point pain perception scale was used.
      Short-term effect was documented after 2 months. The influence of surgical
      history on outcome was examined by using chi-square analysis. The mean duration
      of analgesic effect was calculated by applying a probit survival analysis. Two
      months after undergoing RF treatment, 59% of patients reported satisfactory pain
      reduction. No serious adverse effects were noted. Surgical history was shown to
      have no significant effect on outcome. The long-term half-life time of pain
      reduction was 44.5 months. CONCLUSIONS: The use of RF in the treatment of DRG
      appears to be a useful and safe therapy in patients with chronic spinal pain that
      radiates to the leg. The initial success rate is approximately 60%. It seems to
      lead to a time-limited effect on the target structure, and the mean duration of
      pain reduction is approximately 3.7 years. The mechanism of action remains
      unclear.

PMID- 11302626
TI  - Simultaneous anterior-posterior approach to the thoracic and lumbar spine for the
      radical resection of tumors followed by reconstruction and stabilization.
AB  - OBJECT: Thoracic or lumbar spine malignant tumors involving both the anterior and
      posterior columns represent a complex surgical problem. The authors review the
      results of treating patients with these lesions in whom surgery was performed via
      a simultaneous anterior-posterior approach. METHODS: The hospital records of 26
      patients who underwent surgery via simultaneous combined approach for thoracic
      and lumbar spinal tumors at our institution from July 1994 to March 2000 were
      reviewed. Surgery was performed with the patients in the lateral decubitus
      position for the procedure. The technical details are reported. The mean survival
      determined by Kaplan-Meier analysis was 43.4 months for the 15 patients with
      primary malignant tumors and 22.5 months for the 11 patients with metastatic
      spinal disease. At 1 month after surgery, 23 (96%) of 24 patients who complained
      of pain preoperatively reported improvements (p < 0.001, Wilcoxon signed-rank
      test), and eight (62%) of 13 patients with preoperative neurological deficits
      were functionally improved (p = 0.01). There were nine major complications, five
      minor complications, and no deaths within 30 days of surgery. Two patients (8%)
      later underwent surgery for recurrent tumor. CONCLUSIONS: The simultaneous
      anterior-posterior approach is a safe and feasible alternative for the exposure
      tumors of the thoracic and lumbar spine that involve both the anterior and
      posterior columns. Advantages of the approach include direct visualization of
      adjacent neurovascular structures, the ability to achieve complete resection of
      lesions involving all three columns simultaneously (optimizing hemostasis), and
      the ability to perform excellent dorsal and ventral stabilization in one
      operative session.

PMID- 11302627
TI  - Evaluation of the neuroprotective effects of sodium channel blockers after spinal
      cord injury: improved behavioral and neuroanatomical recovery with riluzole.
AB  - OBJECT: Persistent activation of voltage-sensitive Na+ channels is associated
      with cellular toxicity and may contribute to the degeneration of neural tissue
      following traumatic brain and spinal cord injury (SCI). Pharmacological blockade
      of these channels can attenuate secondary pathophysiology and reduce functional
      deficits acutely. METHODS: To determine the therapeutic effects of Na+ channel
      blockers on long-term tissue sparing and functional neurological recovery after
      traumatic SCI, the authors injected Wistar rats intraperitoneally with riluzole
      (5 mg/kg), phenytoin (30 mg/kg), CNS5546A, a novel Na+ channel blocker (15
      mg/kg), or vehicle (2-HP3CD; 5 mg/kg) 15 minutes after induction of compressive
      SCI at C7-T1. Functional neurological recovery of coordinated hindlimb function
      and strength, assessed 1 week postinjury and weekly thereafter for 6 weeks, was
      significantly enhanced in animals treated with riluzole compared with the other
      treatment groups. Seven weeks postinjury the preservation of residual tissue and
      integrity of descending axons were determined with digital morphometrical and
      fluorescent histochemical analysis. All three Na+ channel blockers significantly
      enhanced residual tissue area at the injury epicenter compared with control.
      Riluzole significantly reduced tissue loss in rostrocaudal regions surrounding
      the epicenter, with overall sparing of gray matter and selective sparing of white
      matter. Also, counts of red nuclei neurons retrogradely labeled with fluorogold
      introduced caudal to the injury site were significantly increased in the riluzole
      group. CONCLUSIONS: Systemic Na+ channel blockers, in particular riluzole, can
      confer significant neuroprotection after in vivo SCI and result in behavioral
      recovery and sparing of both gray and white matter.

PMID- 11302628
TI  - Presence and significance of CD-95 (Fas/APO1) expression after spinal cord
      injury.
AB  - OBJECT: A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in
      the development of apoptosis in a number of tissues. Based on the hypothesis that
      apoptosis is related to cell death after spinal cord injury (SCI), the authors
      studied the presence and distribution of CD95 (Fas/APO1)-positive cells in
      injured spinal cord tissue for the purpose of determining the significance of
      this protein during the early phases of SCI. METHODS: The presence and
      distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were
      studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of
      experimental SCI in rats. Studies were conducted using a monoclonal antibody to
      the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in
      apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number
      of immunostained cells increased for the first 8 hours, at which time the protein
      was expressed in both gray and white matter. From 24 to 72 hours postinjury, the
      number of immunostained cells decreased in the gray matter, but increased in the
      white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but
      some cells in the white matter still exhibited positive immunostaining 1 and 2
      weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells
      in injured spinal cord. CONCLUSIONS: These findings indicate that CD95 (Fas/APO1)
      is expressed after SCI, suggesting a role for this protein in the development of
      apoptosis after trauma and the possibility of a new therapeutic approach to SCI
      based on blocking the CD95 (Fas/APO1) system.

PMID- 11302629
TI  - Cervical spinal motion during intubation: efficacy of stabilization maneuvers in
      the setting of complete segmental instability.
AB  - OBJECT: The purpose of this study was to characterize and compare segmental
      cervical motion during orotracheal intubation in cadavers with and without a
      complete subaxial injury, as well as to examine the efficacy of commonly used
      stabilization techniques in limiting that motion. METHODS: Intubation procedures
      were performed in 10 fresh human cadavers in which cervical spines were intact
      and following the creation of a complete C4-5 ligamentous injury. Movement of the
      cervical spine during direct laryngoscopy and intubation was recorded using video
      fluoroscopy and examined under the following conditions: 1) without
      stabilization; 2) with manual in-line cervical immobilization; and 3) with
      Gardner-Wells traction. Subsequently, segmental angular rotation, subluxation,
      and distraction at the injured C4-5 level were measured from digitized frames of
      the recorded video fluoroscopy. CONCLUSIONS: After complete C4-5 destabilization,
      the effects of attempted stabilization on distraction, angulation, and
      subluxation were analyzed. Immobilization effectively eliminated distraction, and
      diminished angulation, but increased subluxation. Traction significantly
      increased distraction, but decreased angular rotation and effectively eliminated
      subluxation. Orotracheal intubation without stabilization had intermediate
      results, causing less distraction than traction, less subluxation than
      immobilization, but increased angulation compared with either intervention. These
      results are discussed in terms of both statistical and clinical significance and
      recommendations are made.

PMID- 11302630
TI  - The denticulate ligament: anatomy and functional significance.
AB  - OBJECT: The authors conducted a study to examine the detailed anatomy of the
      denticulate ligaments and to assess their classic role in spinal cord stability
      within the spinal canal. METHODS: Detailed observation of the denticulate
      ligaments in 12 adult cadavers was performed. Stress was applied in all major
      planes to discern when the ligaments would become taut, and at the same time,
      gross motion of the cord was observed at sites distal to the stresses applied.
      Tension necessary for avulsion of the ligaments in various areas of the spinal
      cord was also measured. CONCLUSIONS: These results show that the denticulate
      ligaments do not inhibit cord motion to such discrete areas of the cord as was
      once thought. The authors have determined that the ligaments are stronger in the
      cervical region and that they decrease in strength as the spinal cord descends.
      These findings are demonstrative of the denticulate ligaments being more
      resistant to caudal compared with cephalad stresses in the cord. Anterior and
      posterior motion is constrained by these ligaments but to a limited degree,
      especially as one descends inferiorly along the cord. Further embryological and
      functional studies of these ligaments is needed in non-formalin fixed tissues.

PMID- 11302631
TI  - Occipital neuralgia secondary to hypermobile posterior arch of atlas. Case
      report.
AB  - The authors report on the management of occipital neuralgia secondary to an
      abnormality of the atlas in which the posterior arch was separated by a fibrous
      band from the lateral masses, resulting in C-2 nerve root compression. The causes
      and treatments of occipital neuralgia as well as the development of the atlas are
      reviewed.

PMID- 11302632
TI  - Spinal stabilization by using crossed-screw anterior-posterior fixation after
      multisegmental total spondylectomy for thoracic chondrosarcoma. Case report.
AB  - The authors describe the case of a 41-year-old man with high-grade chondrosarcoma
      who presented with a paraspinous mass extending into three thoracic vertebrae
      (T10-12). Crossfixed long anterior and posterior instrumentation was placed after
      three complete spondylectomies (T10-12). This technique augments spinal stability
      with an outrigger effect by using crossfixators placed between paired dorsal
      rods, as well as between the anterior and posterior hardware components. This
      technique may be used as an alternative when multiple vertebrae or all three
      spinal columns are involved by radioresistant malignant tumors in patients in
      whom there is a relatively long life expectancy.

PMID- 11302633
TI  - En bloc removal of the lower lumbar vertebral body for chordoma. Report of two
      cases.
AB  - En bloc removal of the lower lumbar vertebral bodies (VBs) is a major surgical
      challenge. The authors describe the surgical technique used in two patients who
      presented with chordoma confined to the L-5 and L-4 VB, respectively. These
      tumors were diagnosed using magnetic resonance (MR) imaging during investigation
      for back pain. Both patients underwent a combined (two-stage) anterior-posterior
      approach. In the first case the posterior stage of the procedure was followed by
      an anterior retroperitoneal approach, and in the second case a lateral
      retroperitoneal approach was used. Complete en bloc excision of the tumor was
      achieved in each case, even though in the second case the VB fractured when it
      was mobilized. The correlation between the MR imaging findings and surgical
      specimens was remarkable. The authors conclude that en bloc resection is feasible
      in these cases. Because mobilization of the VB is more difficult in the lateral
      approach, the authors favor the anterior retroperitoneal approach. The authors
      anticipate the need for such procedures to increase with the widespread use of MR
      imaging, which demonstrates the extent of these tumors with remarkable accuracy.

PMID- 11302634
TI  - Bilateral posterolateral approach to mirror-image C-2 neurofibromas. Report of
      four cases.
AB  - Multiple nerve root tumors are usually present in patients afflicted with
      neurofibromatosis Type 1. Although rare, upper cervical mirror-image
      neurofibromas have been reported in the medical literature, and their surgical
      management has been addressed in several reports; however, little has been
      mentioned or is known regarding upper cervical or craniocervical stability
      following resection of these tumors. In this report the authors describe four
      cases of large mirror-image C-2 neurofibromas resected in two stages via the
      posterolateral approach. One patient presented with acute neurological
      deterioration after a biopsy sample had been obtained, whereas the other three
      presented with gradual onset of lower-extremity weakness over several months. The
      time interval between the first and second decompressive surgery ranged from 10
      days to 12 weeks. There were no surgery-related complications, and all patients
      recovered motor function in their extremities. During a follow-up period of 16 to
      36 months, there was no clinical or radiological evidence of upper cervical spine
      instability. Although the series is too small to draw any definitive conclusions,
      in the authors' experience the posterolateral approach provides a direct route
      for the successful surgical treatment of bilateral craniocervical nerve root
      tumors without destabilizing the upper cervical segments.

PMID- 11302635
TI  - Amyloidoma of the thoracic spine. Case report.
AB  - The authors report the case of a patient with amyloidoma of the thoracic spine. A
      34-year-old man presented with a 2-month history of upper-back pain, bilateral
      lower-extremity weakness, and numbness below the nipple. A computerized
      tomography study revealed an extradural mass with destruction of the T-2 lamina
      and pedicle. Intraoperatively, there was a pinkish, partially suctionable mass
      infiltrating the muscle plane and causing destruction of the T-2 lamina.
      Histological examination showed typical amyloid masses that demonstrated apple
      green double refraction on examination of the Congo red-stained section under
      polarized light. Amyloidomas are rare benign lesions that, unlike other forms of
      amyloidosis, have an excellent prognosis. A cure is possible with complete
      resection of the mass.

PMID- 11302636
TI  - Pathological fracture through a C-6 aneurysmal bone cyst. Case report.
AB  - The authors describe the case of an 18-year-old man who presented with complaints
      of weakness and paresis in his arms following an injury. Radiological examination
      demonstrated an aneurysmal bone cyst of C-6. The patient underwent a two-stage
      operation. Satisfactory results were obtained after complete resection of the
      lesion, laminoplasty, and anterior fusion without placement of instrumentation.
      The authors consider a two-stage operation supplemented by fusion without
      instrumentation to be the best treatment for young patients with aneurysmal bone
      cysts occurring at C-6.

PMID- 11302637
TI  - Intramedullary neurenteric cysts of the spine. Case report and review of the
      literature.
AB  - This case of a 68-year-old woman with a low-thoracic intramedullary neurenteric
      cyst is notable for clinical presentation, cyst location, intraoperative
      findings, and imaging characteristics. The patient's postoperative course was
      complicated by neurological deterioration and a neuropathic pain syndrome.
      Potential causes of these complications are discussed, as are possible ways to
      reduce the risk of their occurrence.

PMID- 11302638
TI  - Oncocytoma of the spinal cord. Case report.
AB  - The authors report a case of oncocytoma arising from the spinal cord in a 40-year
      old woman who presented with the complaints of gradual difficulty in walking. The
      excised tumor was exclusively composed of polygonal cells with abundant
      homogeneous eosinophilic cytoplasms. Electron microscopy study showed densely
      packed swollen mitochondria and frequent desmosomes. The histological and
      ultrastructural findings were consistent with a diagnosis of oncocytoma. To the
      authors' knowledge, this represents the first reported case of oncocytoma of the
      spinal cord.

PMID- 11302639
TI  - Isolated carcinoid tumor of the terminal filum. Case report.
AB  - The authors describe a patient with neurological symptoms caused by a carcinoid
      tumor at the terminal filum without carcinoid "flushing" syndrome or
      endocrinological abnormalities. The patient underwent subtotal resection and
      adjuvant radiotherapy. Extensive postoperative workup revealed no primary site of
      disease. To the authors' knowledge, this patient represents the first case of
      terminal filum carcinoid tumor.

PMID- 11302640
TI  - Acute posttraumatic spinal cord herniation. Case report and review of the
      literature.
AB  - Transdural herniations of the spinal cord are rare, and those occurring acutely
      after a spinal cord injury (SCI) are particularly unusual. In this report, the
      authors present the case of acute posttraumatic spinal cord herniation in a
      patient who sustained severe polytraumatic injuries. The clinical manifestations
      were acute flaccid paralysis of the right leg and rapidly progressive
      sensorimotor deficits of the contralateral leg. The herniation was surgically
      reduced. Postoperatively left leg paralysis was completely resolved. The authors
      review the pertinent literature, and suggest that, with regard to another
      underlying pathophysiological mechanism, cases of acute posttraumatic spinal cord
      herniation should be differentiated from those "posttraumatic" cases in which
      herniation of the spinal cord occurs years or even decades after the traumatic
      event. To the best of the authors' knowledge, only one similar case has been
      previously reported. They conclude that acute posttraumatic spinal cord
      herniation should be included in the differential diagnosis of acute neurological
      deterioration after SCI.

PMID- 11302641
TI  - Subarachnoid-pleural fistula treated with noninvasive positive-pressure
      ventilation. Case report.
AB  - The authors describe the case of a 24-year-old man who underwent an L-1
      corpectomy for spinal decompression and stabilization following an injury that
      caused an L-1 burst fracture. Postoperatively, an accumulation of spinal fluid
      developed in the pleural space, which was refractory to 1 week of thoracostomy
      tube drainage and lumbar cerebrospinal fluid (CSF) diversion. The authors then
      initiated a regimen of positive-pressure ventilation in which a bi-level positive
      airway pressure (PAP) mask was used. After 5 days, the CSF collection in the
      pleural space resolved. Use of a bi-level PAP mask represents a safe, noninvasive
      method of reducing the negative intrathoracic pressure that promotes CSF leakage
      into the pleural cavity and may be a useful adjunct in the treatment of
      subarachnoid-pleural fistula.

PMID- 11302642
TI  - Use of folded vascularized rib graft in anterior fusion after treatment of
      thoracic and upper lumbar lesions. Technical note.
AB  - For lesions involving the anterior and/or middle column of the spine, an anterior
      approach is adequate for curetting the lesion and restoring spinal stability.
      Materials such as autogenous bone grafts, cages with bone chips, some artificial
      materials, or allografts are used as strut materials. Rib material is usually
      removed when the anterior approach is conducted for thoracic or thoracolumbar
      lesions. A rib itself is not rigid enough to support the load, and a bone union
      is not easily obtained. The purpose of this paper is to describe a method of
      grafting vascularized rib in folded form to fill the defects left after removal
      of a spinal lesion. The rib, with the artery and vein at two levels cranial to
      the involved vertebral body, was isolated from surrounding tissues such as the
      intercostal nerve, muscles, and pleura. After curetting the lesion, the rib was
      folded into three or four pieces to a length adequate to fill the defect and
      inserted as a pedicled vascularized graft. A total of 23 cases, including 14 men
      and nine women, underwent surgery in which this grafting technique was used. The
      pathological conditions requiring anterior decompression and fusion were spinal
      trauma in nine cases, spinal infection in six cases, osteoporotic fracture in
      seven cases, and spinal metastasis in one case. In all cases a solid bone union
      was obtained and all infections resolved. With vascularized rib graft folded into
      three to four pieces, solid bone union can be obtained without use of any other
      grafted materials even in cases of infection and osteoporosis.

PMID- 11302643
TI  - Use of a guide device to place pedicle screws in the thoracic spine: a cadaveric
      study. Technical note.
AB  - In this cadaveric study, the safety and accuracy of a specially designed guide
      device for the placement of thoracic pedicle screws was investigated in a normal
      anatomical situation. Five embalmed human cadaveric thoracic spines (T1-12) were
      used for the study of transpedicular screw placement in the thoracic spine.
      Overall 120 screws were placed at all thoracic levels. The screws were inserted
      bilaterally in the thoracic pedicles by using a specially designed guide device.
      No radiographs or other imaging studies were obtained. Following screw placement,
      computerized tomography scans were performed to evaluate the accuracy of the
      pedicle screw positioning. Seven (5.8%) of the screws penetrated the pedicle wall
      or the vertebral body (VB) cortex. Two screws (1.7%) penetrated the medial wall
      of the pedicle. Two screws (1.7%) penetrated the lateral wall of the pedicle, and
      one screw (0.8%) penetrated the lateral wall of the pedicle and the anterior VB
      cortex simultaneously. Two screws (1.7%) penetrated the anterior VB cortex.
      Compared with the results of other studies, the findings here indicate that using
      this device to guide the placement of thoracic pedicle screws can significantly
      reduce the incidence of pedicle penetration, particularly in the medial wall.

PMID- 11302644
TI  - Infantile spinal cord meningioma. Case illustration.

PMID- 11302645
TI  - Syringoperitoneal shunt migration. Case illustration.

PMID- 11302646
TI  - Intradural sacral chordoma. Case illustration.

PMID- 11302647
TI  - Lower medulla and upper cervical cord compression caused by bilateral vertebral
      artery. Case illustration.

PMID- 11302648
TI  - Calcitonin and spinal fusion.
AB  - The authors report on the efficacy of nonsurgical treatment of an older patient
      with a fractured odontoid process. The patient, an 85-year-old woman, had
      multiple medical problems that put her at an increased surgery-related risk.
      Therefore, an alternative approach was elected, including immobilization with a
      Philadelphia collar and the provision of calcitonin nasal spray. Bone union and
      clinical recovery were achieved within 8 weeks of initiating the nasal calcitonin
      therapy (12 weeks postinjury). Considering the patient's age, comorbidities, and
      the severity of the fracture, the recovery period was unusually short. The
      authors believe that calcitonin played a pivotal role in the healing process of
      the fractured odontoid bone. There is no question that the fusion in this patient
      could be unrelated to the medical therapy. This description of one patient, as
      well as the lack of a large randomized study, precludes any scientific
      conclusions. Nevertheless, the authors believe that the development of a
      successful fusion in this high-risk patient should be reported as an observation
      that merits confirmation and study. The authors also discuss the physiological
      effects of calcitonin and the research and clinical experience with this hormone
      in different conditions affecting bone.

PMID- 11302649
TI  - Calcitonin and spinal fusion.

PMID- 11302650
TI  - Spinal cord injury.
AB  - OBJECT: It is known that the spinal cord can sustain traumatic injury without
      associated injury of the spinal column in some conditions, such as a flexible
      spinal column or preexisting narrowed spinal canal. The purpose of this study was
      to characterize the clinical features and to understand the mechanisms in cases
      of acute cervical cord injury in which fracture or dislocation of the cervical
      spine has not occurred. METHODS: Eighty-nine patients who sustained an acute
      cervical cord injury were treated in our hospitals between 1990 and 1998. In 42
      patients (47%) no bone injuries of the cervical spine were demonstrated, and this
      group was retrospectively analyzed. There were 35 men and seven women, aged 19 to
      81 years (mean 58.9 years). The initial neurological examination indicated
      complete injury in five patients, whereas incomplete injury was demonstrated in
      37. In the majority of the patients (90%) the authors found degenerative changes
      of the cervical spine such as spondylosis (22 cases) or ossification of the
      posterior longitudinal ligament (16 cases). The mean sagittal diameter of the
      cervical spinal canal, as measured on computerized tomography scans, was
      significantly narrower than that obtained in the control patients. Magnetic
      resonance (MR) imaging revealed spinal cord compression in 93% and paravertebral
      soft-tissue injuries in 58% of the patients. CONCLUSIONS: Degenerative changes of
      the cervical spine and developmental narrowing of the spinal canal are important
      preexisting factors. In the acute stage MR imaging is useful to understand the
      level and mechanisms of spinal cord injury. The fact that a significant number of
      the patients were found to have spinal cord compression despite the absence of
      bone injuries of the spinal column indicates that future investigations into
      surgical treatment of this type of injury are necessary.

PMID- 11302651
TI  - Comprehensive assessment of hemorrhage risks and outcomes after stereotactic
      brain biopsy.
AB  - OBJECT: Stereotactic brain biopsy has played an integral role in the diagnosis
      and management of brain lesions. At most centers, imaging studies following
      biopsy are rarely performed. The authors prospectively determined the acute
      hemorrhage rate after stereotactic biopsy by performing immediate postbiopsy
      intraoperative computerized tomography (CT) scanning. They then analyzed factors
      that may influence the risk of hemorrhage and the diagnostic accuracy rate.
      METHODS: Five hundred consecutive patients undergoing stereotactic brain biopsy
      underwent immediate postbiopsy intraoperative CT scanning. Before surgery,
      routine preoperative coagulation studies were performed in all patients. All
      medical charts, laboratory results, preoperative imaging studies, and
      postoperative imaging studies were reviewed. In 40 patients (8%) hemorrhage was
      detected using immediate postbiopsy intraoperative CT scanning. Neurological
      deficits developed in six patients (1.2%) and one patient (0.2%) died.
      Symptomatic delayed neurological deficits developed in two patients (0.4%),
      despite the fact that the initial postbiopsy CT scans in these cases did not show
      acute hemorrhage. Both patients had large intracerebral hemorrhages that were
      confirmed at the time of repeated imaging. The results of a multivariate logistic
      regression analysis of the risk of postbiopsy hemorrhage of any size showed a
      significant correlation only with the degree to which the platelet count was
      below 150,000/mm3 (p = 0.006). The results of a multivariate analysis of a
      hemorrhage measuring greater than 5 mm in diameter also showed a correlation
      between the risk of hemorrhage and a lesion location in the pineal region (p =
      0.0086). The rate at which a nondiagnostic biopsy specimen was obtained increased
      as the number of biopsy samples increased (p = 0.0073) and in accordance with
      younger patient age (p = 0.026). CONCLUSIONS: Stereotactic brain biopsy was
      associated with a low likelihood of postbiopsy hemorrhage. The risk of hemorrhage
      increased steadily as the platelet count fell below 150,000/mm3. The authors
      found a small but definable risk of delayed hemorrhage, despite unremarkable
      findings on an immediate postbiopsy head CT scan. This risk justifies an
      overnight hospital observation stay for all patients after having undergone
      stereotactic brain biopsy.

PMID- 11302652
TI  - A 10-year follow-up review of patients who underwent Leksell's posteroventral
      pallidotomy for Parkinson disease.
AB  - OBJECT: The clinical condition of patients with Parkinson disease (PD) who had
      undergone posteroventral pallidotomy (PVP) between 1985 and 1990 was evaluated at
      a mean of 10 years postsurgery. These patients were part of a larger series
      described in the first paper on Leksell's PVP that was published in 1992.
      METHODS: Thirteen consecutive patients who had undergone pallidotomy at the
      University Hospital of Northern Sweden were tracked. Hospital and clinic records
      that had been updated regularly by the patients' various neurologists,
      geriatricians, and other clinicians were reviewed. Emphasis was placed on
      assessing the evolution of PD symptoms after surgery, and changes in the general
      health and social condition of the patients. The mean follow-up duration was 10.5
      years (range 3-13.5 years). Five patients underwent a total of seven subsequent
      surgeries for their PD, 4 months to 11 years after the initial pallidotomy. The
      mean Hoehn and Yahr stage was 3 at the first surgery and 3.7 at the last follow
      up review (p < 0.005). Dosages of levodopa and dopamine agonists were increased
      in all patients, without recurrence or induction of dyskinesias contralateral to
      the pallidotomy. Contralateral tremor, if it was initially controlled by surgery,
      remained improved. However, most patients exhibited a gradual recurrence of
      akinesia and an increase in gait freezing. Cognitive decline and presentation
      with diseases unrelated to PD were not uncommon. CONCLUSIONS: The long-term
      effect of PVP on dyskinesias was not only curative but also appeared to be
      prophylactic. Contralateral tremor was improved in the majority of patients,
      although additional surgeries for PD were needed in some patients. Further
      progression of axial and akinetic symptoms, and an eventual decline in cognition
      together with other concomitant illnesses, contributed to increased disability in
      several patients.

PMID- 11302653
TI  - Cerebral hemodynamics in patients with carotid artery occlusion and contralateral
      moderate or severe internal carotid artery stenosis.
AB  - OBJECT: The purpose of this study was to evaluate cerebral hemodynamics in
      patients suffering from occlusion of the carotid artery (CA) and contralateral CA
      stenosis. METHODS: Using transcranial Doppler ultrasonography, the
      cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was
      evaluated by calculating the breath-holding index (BHI) of 69 symptomatic
      patients suffering from internal CA (ICA) occlusion and moderate or severe
      contralateral ICA stenosis. To evaluate which variables influenced BHIs
      ipsilateral to the site of ICA occlusion, a multiple stepwise linear regression
      analysis was performed that included the following factors: patient age,
      percentage of contralateral ICA stenosis, contralateral BHI, number of collateral
      pathways, and presence of hypertension, diabetes, smoking, and hyperlipidemia. An
      analysis of variance was conducted to evaluate the impact of the type of
      collateral vessels on the BHI. A regression analysis showed that the BHI
      ipsilateral to the site of ICA occlusion could be accounted for by the
      contralateral BHI (which was entered at the first step of the analysis, p <
      0.001) and by the number of collateral pathways (which was entered at the second
      step, p = 0.033). Neither the degree of contralateral ICA stenosis nor the other
      variables could be added to improve the model. The analysis demonstrated that the
      absence of collateral pathways and the presence of the anterior communicating
      artery (ACoA) alone were associated with lower BHI values than those found in the
      presence of two or three collateral vessels, regardless of the presence of an
      anterior collateral pathway. CONCLUSIONS: On the basis of these data one can
      infer that the cerebral hemodynamic status of patients with occlusive disease of
      the CA is influenced by individual anatomical and functional characteristics.
      Because improvement in contralateral hemodynamics after surgical correction of an
      ICA stenosis can only be expected in the presence of an ACoA, the planning of
      strategies for influencing cerebral blood flow distal to an ICA occlusion and, in
      particular, the consideration of a contralateral carotid endarterectomy, should
      be preceded by a careful evaluation of the intracranial hemodynamic adaptive
      status of the patient. Particular attention should be paid to cerebrovascular
      reactivity and the number and type of collateral vessels that are present.

PMID- 11302654
TI  - Ischemic complications of surgery for anterior choroidal artery aneurysms.
AB  - OBJECT: Anterior choroidal artery (AChA) aneurysms account for 4% of all
      intracranial aneurysms. The surgical approach is similar to that for other
      supraclinoid carotid artery lesions, but surgery may involve a higher risk of
      debilitating ischemic complications because of the critical territory supplied by
      the AChA. METHODS: Between 1968 and 1999, 51 AChA aneurysms in 50 patients were
      treated using craniotomy and clipping at the Mayo Clinic. There were 22 men (44%)
      and 28 women (56%) whose average age was 53 years (range 27-79 years). Twenty
      four AChA aneurysms (47%) had hemorrhaged; nine patients (18%) had subarachnoid
      hemorrhage from another aneurysm. Three AChA aneurysms (6%) were associated with
      symptoms other than rupture. Forty-one patients (82%) achieved a Glasgow Outcome
      Scale (GOS) score of 4 or 5 at long-term follow up. The surgical mortality rate
      was 4%, and major surgical morbidity (GOS < or = 3) was 10%. Eight patients (16%)
      had clinically and computerized tomography-demonstrated AChA territory infarcts.
      Five of these strokes manifested in a delayed fashion 6 to 36 hours after the
      operation, and progressed from mild to complete deficit over hours. In 41
      patients the aneurysm arose from the internal carotid artery adjacent to the
      AChA, and in nine patients the aneurysm arose directly from the origin of the
      AChA itself; four of these nine patients had postoperative infarction.
      CONCLUSIONS: Surgical treatment of AChA aneurysms involves a significant risk of
      debilitating ischemic complications. Most postoperative strokes occur in a
      delayed fashion, offering a potential therapeutic window. Patients with aneurysms
      arising from the AChA itself have an extremely high risk for postoperative
      stroke.

PMID- 11302655
TI  - Effects of ventriculoperitoneal shunt removal on cerebral oxygenation and brain
      compliance in chronic obstructive hydrocephalus.
AB  - OBJECT: The pathophysiology of shunt malfunction has not been fully examined,
      probably because of the paucity of appropriate animal models. Using a canine
      model of chronic obstructive hydrocephalus, the effects of shunt placement and
      removal on physiological parameters were evaluated. METHODS: Fifteen dogs, nine
      in which chronic hydrocephalus was induced and six controls, were used in the
      experiment. Thirteen weeks after the induction of hydrocephalus, intracranial
      pressure (ICP), tissue and cerebrospinal fluid O2 saturation, response to
      hyperventilation, and brain compliance at low (5-15 mm Hg) and high (15-25 mm Hg)
      pressures were measured (untreated stage). Following this procedure,
      ventriculoperitoneal shunts were implanted in the dogs suffering from
      hydrocephalus. Two weeks later, the same series of measurements were repeated
      (shunted stage), following which the shunt systems were removed. One week after
      shunt removal, the last measurements were obtained (shunt-removed stage). All
      dogs underwent magnetic resonance imaging four times: before induction of
      hydrocephalus and before each measurement. All dogs with hydrocephalus also had
      ventriculomegaly (1.42 +/- 0.89 ml before induction of hydrocephalus compared
      with 3.4 +/- 1.64 ml 13 weeks after induction, p = 0.0064). In dogs in the
      untreated hydrocephalus stage, ICP remained within the normal range (8.33 +/-
      2.60 mm Hg)--although it was significantly higher than that in the control group
      (5 +/- 1.41 mm Hg, p = 0.014). Tissue O2 saturation in the dogs in the
      hydrocephalus group (26.1 +/- 5.33 mm Hg) was lower than that in the dogs in the
      control group (48.7 +/- 4.27 mm Hg, p < 0.0001). After the dogs underwent shunt
      placement, significant improvement was observed in their ICP (5.22 +/- 2.17 mm
      Hg, p = 0.012) and tissue O2 saturation (35.2 +/- 6.80 mm Hg, p = 0.0084).
      However, removal of the shunt reversed these improvements back to the preshunt
      status. Hyperventilation induced significant decreases in ICP and O2 saturation
      at every measurement time and induced a significant decrease in tissue O2
      saturation during the shunted stage, but not during the untreated and shunt
      removed stages. Brain compliance measured at high pressure demonstrated a
      significant gradual decrease at every measurement. CONCLUSIONS: In chronic
      obstructive hydrocephalus, shunt placement improves ICP and cerebral oxygenation
      as well as the response to hyperventilation in the tissue. Shunt removal reverses
      these improvements back to levels present during the untreated stage. The
      decrease in brain compliance may be one of the factors responsible for symptoms
      in shunt malfunction.

PMID- 11302656
TI  - Angiographic evaluation of middle cerebral artery reperfusion caused by platelet
      glycoprotein IIb/IIIa receptor complex antagonist murine 7E3 F(ab')2 in a model
      of focal cerebral ischemia in rats.
AB  - OBJECT: Antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex
      are currently used for the treatment of acute coronary syndromes. The platelet
      GPIIb/IIIa mediates platelet aggregation, and blocking this receptor complex can
      reduce or prevent arterial thrombosis. To study the recanalization efficacy of a
      GPIIb/IIIa antagonist in treating cerebral ischemia, we investigated the
      therapeutic effects of murine 7E3 F(ab'), in a focal embolic cerebral ischemia
      model in rats. METHODS: Focal cerebral ischemia was produced by introducing an
      autologous thrombus into the right side of the middle cerebral artery (MCA).
      Thirty male Wistar rats were randomly divided into three groups of 10 rats each:
      control, 7E3 F(ab')2 administered 1 hour postischemia, and 7E3 F(ab')2
      administered 3 hours postischemia. Animals in the therapeutic groups received
      intravenous infusion of 6 mg/kg 7E3 F(ab')2 at 1 or 3 hours following cerebral
      embolization. Brain infarct volume, neurobehavioral scores, duration of bleeding,
      and findings on angiograms of the MCA (before and after infusion) were assessed
      in all animals. Angiographic evaluation revealed full MCA recanalization in three
      of 10 animals in each 7E3 F(ab')2 treatment group. Animals in these groups
      exhibited a significant reduction in infarct volume when compared with animals in
      the control group: 1) infarct volume 1 hour postischemia, 22 +/- 13.9% (p =
      0.005); 2) infarct volume 3 hours postischemia, 22.1 +/- 14.8% (p = 0.008); and
      3) infarct volume in control animals, 42.4 +/- 16%. Postischemia treatment with
      7E3 F(ab')2 also improved the animal's neurobehavioral performance. The duration
      of bleeding significantly increased by more than two times, but there was no
      associated increase in intracerebral hemorrhage in any group. CONCLUSIONS: On the
      basis of their findings, the authors conclude that murine 7E3 F(ab'), is a potent
      and safe antiplatelet agent in this experimental focal embolic cerebral ischemia
      model. Neuronal lesions were significantly reduced when the treatment was delayed
      up to 3 hours.

PMID- 11302657
TI  - Intracranial bone marrow transplantation after traumatic brain injury improving
      functional outcome in adult rats.
AB  - OBJECT: The authors tested the hypothesis that intracranial bone marrow (BM)
      transplantation after traumatic brain injury (TBI) in rats provides therapeutic
      benefit. METHODS: Sixty-six adult Wistar rats, weighing 275 to 350 g each, were
      used for the experiment. Bone marrow prelabeled with bromodeoxyuridine (BrdU) was
      harvested from tibias and femurs of healthy adult rats. Other animals were
      subjected to controlled cortical impact, and BM was injected adjacent to the
      contusion 24 hours after the impact. The animals were killed at 4, 7, 14, or 28
      days after transplantation. Motor function was evaluated both before and after
      the injury by using the rotarod test. After the animals had been killed, brain
      sections were examined using hemotoxylin and eosin and immunohistochemical
      staining methods. Histological examination revealed that, after transplantation,
      BM cells survived, proliferated, and migrated toward the injury site. Some of the
      BrdU-labeled BM cells were reactive, with astrocytic (glial fibrillary acid
      protein) and neuronal (NeuN and microtubule-associated protein) markers.
      Transplanted BM expressed proteins phenotypical of intrinsic brain cells, that
      is, neurons and astrocytes. A statistically significant improvement in motor
      function in rats that underwent BM transplantation, compared with control rats,
      was detected at 14 and 28 days posttransplantation. CONCLUSIONS: On the basis of
      their findings, the authors assert that BM transplantation improves neurological
      outcome and that BM cells survive and express nerve cell proteins after TBI.

PMID- 11302658
TI  - Reduced tumorigenicity of rat glioma cells in the brain when mediated by
      hygromycin phosphotransferase.
AB  - OBJECT: A variant of C6 glioma cells, C6R-G/H cells express hygromycin
      phosphotransferase (HPT) and appear to have reduced tumorigenicity in the
      embryonic brain. The goal of this study was to investigate their reduced capacity
      to generate tumors in the adult rat brain. METHODS: Cell lines were implanted
      into rat brains and tumorigenesis was evaluated. After 3 weeks, all rats with C6
      cells showed signs of neurological disease, whereas rats with C6R-G/H cells did
      not and were either killed then or allowed to survive until later. Histological
      studies were performed to analyze tumor size, malignancy, angiogenesis, and cell
      proliferation. Cells isolated from rat brain tumors were analyzed for mutation to
      HPT by testing their sensitivity to hygromycin. CONCLUSIONS: The results indicate
      that HPT suppresses tumor formation. Three weeks after implantation, only 44% of
      animals implanted with C6R-G/H cells developed tumors, whereas all animals that
      received C6 glioma cells developed high-grade gliomas. The C6R-G/H cells filled a
      20-fold smaller maximal cross-sectional area than the C6 cells, and exhibited
      less malignant characteristics, including reduced angiogenesis, mitosis, and cell
      proliferation. Similar results were obtained in the brain of nude rats,
      indicating that the immune system did not play a significant role in suppressing
      tumor growth. The combination of green fluorescent protein (GFP) and HPT was more
      effective in suppressing tumorigenesis than either plasmid by itself, indicating
      that the GFP may protect against inactivation of the HPT. Interestingly.
      hygromycin resistance was lost in tumor cells that were recovered from a group of
      animals in which C6R-G/H cells formed tumors, confirming the correlation of HPT
      with reduced tumorigenicity.

PMID- 11302659
TI  - Long-term survival of a patient with giant cell glioblastoma. Case report.
AB  - The authors report on a patient who had undergone resection of a left-sided
      temporal giant cell glioblastoma at the age of 69 years and who survived for more
      than 17 years. This man had not undergone postoperative radiotherapy or adjuvant
      chemotherapy. He died at the age of 86 years without clinical evidence of tumor
      recurrence. Histologically, the lesion was characterized by highly pleomorphic
      tumor cells (including bizarre multinucleated giant cells) with high mitotic
      activity, large necroses, and prominent mononuclear infiltration. A point
      mutation in the TP53 tumor suppressor gene (c.524G>A; R175H) and no epidermal
      growth factor receptor gene amplification were revealed on molecular genetic
      analysis. No diagnostic chromosomal imbalances were identified on comparative
      genomic hybridization, although the average ratio profile for chromosome 10
      indicated loss of 10p15 in a subpopulation of tumor cells. This patient is
      exceptional because tumor resection, probably in conjunction with a marked
      antitumor immune response, apparently resulted in eradication of the lesion.

PMID- 11302660
TI  - Extraaxial primitive neuroectodermal tumor mimicking a vestibular schwannoma:
      diagnostic and therapeutic difficulties. Report of two cases.
AB  - Extraaxial cerebellopontine angle (CPA) medulloblastomas and other primitive
      neuroectodermal tumors (PNETs) are rare tumors. The authors report on two
      patients with PNETs who presented with progressive audiovestibular symptoms. In
      each case magnetic resonance (MR) imaging revealed an extraaxial lesion that
      filled the internal auditory meatus and exhibited the neuroimaging features of a
      vestibular schwannoma (VS). No high signal intensity was apparent in either the
      brainstem or adjacent cerebellum on T2-weighted MR images. Surgery with maximum
      resection (total in one case and subtotal in the other) was performed, followed
      by craniospinal radiotherapy. One year postoperatively, both patients were free
      from tumor. A CPA PNET mimicking a VS is a rare entity, the diagnosis of which is
      important because its treatment differs dramatically from that of VS, including
      prescribed surgery followed by conventional craniospinal radiotherapy.

PMID- 11302661
TI  - Postoperative spinal seeding of craniopharyngioma. Case report.
AB  - The authors present a case of postoperative spinal seeding of papillary
      craniopharyngioma. This 27-year-old man who had previously undergone subtotal
      removal of a suprasellar craniopharyngioma was admitted because of low-back and
      right leg pain. Results of neurological examination showed a limitation in
      straight-leg raising in the right side with no sensorimotor changes. Magnetic
      resonance imaging of the lumbar spine demonstrated multiple enhanced intradural
      extramedullary masses causing spinal cord compression. Pathological examination
      of the tumor tissue obtained via laminectomy revealed papillary
      craniopharyngioma, which had the same histological features as those of the
      previous suprasellar tumor. Several ectopic recurrences of craniopharyngioma have
      been reported; however, the authors believe that this is the first published
      report of the spinal seeding of craniopharyngioma.

PMID- 11302662
TI  - Artificial elevation of brain tissue glycerol by administration of a glycerol
      containing agent. Case report.
AB  - In recent years the development of secondary brain damage and derangement of
      neurochemical parameters after severe head injury has been monitored using
      microdialysis. Provided the blood-brain barrier is intact, glycerol is regarded
      as a potential marker for membrane phospholipid degradation. The authors report a
      case in which marked elevation of interstitial glycerol was induced after
      exogenous administration of a glycerol-containing agent. A 25-year-old man was
      injured in a motorcycle accident and was admitted to the authors' institution
      with a unilateral dilated and fixed pupil and a Glasgow Coma Scale score of 3.
      Computerized tomography scans revealed a large subdural hematoma on the left
      side, subsequent midline shift, and generalized edema. Emergency craniotomy was
      performed for evacuation of the hematoma. The patient was prepared for
      multisensory monitoring and a microdialysis catheter was inserted into his left
      frontal lobe. After a routine enema containing 85% glycerol had been
      administered, the authors measured a marked increase in glycerol in the
      dialysate. This occurred while the patient was in as stable a condition as could
      be expected given the circumstances. The increase in interstitial glycerol in the
      injured tissue was most likely due to an impaired blood-brain barrier. Thus, the
      interstitial glycerol concentration had been corrupted by exogenous glycerol, and
      the marker properties of glycerol in this case became questionable. Consequently,
      administration of glycerol, which is frequently found in various infusions and
      emulsions, can promote secondary brain damage by adversely shifting osmotic
      gradients.

PMID- 11302663
TI  - Median nerve compression caused by a venous aneurysm. Case report.
AB  - A rare case of peripheral-nerve compression in the upper arm caused by a
      spontaneous venous aneurysm is reported. The apparent dysfunction of the median
      nerve led to various vain surgical explorations of the nerve at different levels.
      The real localization of nerve entrapment was identified by a thorough clinical
      examination, and sonography yielded a correct diagnosis. Surgical resection of
      the venous aneurysm resulted in complete relief of pain. To the authors'
      knowledge, this is the first report of a spontaneous venous malformation in the
      upper arm causing focal neuropathy.

PMID- 11302664
TI  - Radial nerve palsy caused by spontaneously occurring nerve torsion. Case report.
AB  - An 18-year-old man presented with a spontaneously occurring radial nerve palsy
      that spared the triceps muscle. At surgery, the portion of the radial nerve
      located at the midarm level had an hourglass-like appearance. Under
      magnification, an external-internal neurolysis of the narrowed portion of the
      hourglass-shaped portion revealed nerve torsion. Straightening of the twisted
      nerve and fixation accomplished using epiperineurium-fascia stitches to avoid a
      new torsion resulted in complete functional recovery of the radial nerve.

PMID- 11302665
TI  - Ocular symptoms associated with a dural arteriovenous fistula involving the
      hypoglossal canal: selective transvenous coil embolization. Case report.
AB  - The hypoglossal canals are an unusual location for dural arteriovenous fistulas
      (AVFs) to appear. One previous report of dural AVFs involving the hypoglossal
      canal has been published. In the present paper, the authors describe a dural AVF
      within the hypoglossal canal, which presented with ocular symptoms and was
      successfully treated by selective transvenous embolization. Magnetic resonance
      imaging and contralateral carotid arteriography were useful for determination of
      the exact location of the fistulous pouch, which was later packed with coils.
      Selective transvenous coil embolization with careful assessment of the location
      and pattern of the venous drainage of the dural AVF is a safe and effective
      treatment.

PMID- 11302666
TI  - Spontaneous vertex extradural hematoma: considerations about causes. Case report
      and review of the literature.
AB  - A 36-year-old woman with an uneventful medical history was admitted to the
      emergency department following an initial generalized seizure. Neuroimaging
      workup disclosed a homogeneous mass at the vertex, which first was diagnosed as
      vertex meningioma. Anticonvulsant drug therapy was administered and the patient
      was discharged. Two months later the patient was examined in our neurosurgery
      department for additional therapeutic recommendations. A repeated neuroimaging
      examination showed considerable regression of the lesion. The findings on
      magnetic resonance imaging were consistent with those of a regressing extradural
      hematoma (EDH). A complete blood-coagulation study displayed no evidence of
      abnormality. Thorough questioning of the patient revealed no history of
      pericranial infection or head trauma occurring within the last 2 years. The final
      diagnosis was spontaneously occurring vertex EDH. In this report the authors
      describe the clinical and neuroimaging features of the case as well as the
      management strategy, and discuss etiological aspects within the context of a
      careful review of the literature.

PMID- 11302667
TI  - Delayed appearance of a traumatic intracranial aneurysm. Case report and review
      of the literature.
AB  - Giant traumatic intracranial aneurysms are rare, and thus their incidence and
      clinical behavior are poorly understood. In most cases, traumatic aneurysms
      develop and become symptomatic within months following injury. The authors
      present the case of a 46-year-old war veteran, in whom a giant internal carotid
      artery aneurysm developed as a result of a penetrating cranial shrapnel injury
      sustained 25 years earlier during the Vietnam war. The aneurysm had not been
      evident on previous imaging studies. At surgery, a piece of shrapnel was found
      embedded in the dome of the aneurysm. The presentation, diagnosis, management,
      and treatment options related to this lesion are discussed.

PMID- 11302668
TI  - Diagnostic and surgical strategies for intractable spontaneous intracranial
      hypotension. Case report.
AB  - The authors present the case of a 55-year-old man suffering from intractable
      spontaneous intracranial hypotension, in whom conservative treatment with 19
      weeks of bed rest was not effective. In this period the patient twice underwent
      surgery for bilateral chronic subdural hematoma, a complication of spontaneous
      intracranial hypotension. Conventional radionuclide cisternography, magnetic
      resonance imaging, and computerized tomography myelography did not demonstrate
      cerebrospinal fluid (CSF) leakage. Repeated radionuclide cisternography with the
      patient in an upright position revealed leakage of the tracer at upper cervical
      levels. Computerized tomography myelography with breath holding also showed CSF
      leakage of the contrast medium bilaterally at upper cervical levels. The patient
      underwent surgery, and bilateral C-2 and C-3 spinal nerve root pouches were
      sealed off from the subarachnoid space with oxidized cellulose cotton and fibrin
      glue. Epiarachnoid spaces around the root sleeves were also sealed to ensure
      complete resolution of the CSF leakage. After the surgery, the patient was
      completely free of the disease. In the case of intractable persistent spontaneous
      intracranial hypotension, surgical treatment is preferable to long-term
      conservative management. To identify CSF leakage, radionuclide cisternography
      with the patient in the upright position is useful. When obvious leakage is
      encountered, surgical sealing of the lesion should be performed via a
      subarachnoid approach.

PMID- 11302669
TI  - Endovascular treatment of cranial venous sinus obstruction resulting in
      pseudotumor syndrome. Report of three cases.
AB  - It is probable that a significant number of cases of pseudotumor syndrome (PTS)
      occur because of cranial venous outflow obstruction, yet reports of direct
      treatment of the obstruction are few and inconclusive. In this study the authors
      report three cases of PTS with angiographically confirmed venous sinus
      obstruction treated by direct, endovascular procedures; urokinase infusion in two
      and balloon venoplasty in one. Two patients suffered transient complications that
      resolved satisfactorily. All three showed initial resolution of the signs and
      symptoms of PTS but one relapsed after 8 months and required surgical treatment.
      The possible role and methods of treatment of cranial venous outflow obstruction
      in PTS are discussed.

PMID- 11302670
TI  - Failure of surgical decompression for a presumed case of piriformis syndrome.
      Case report.
AB  - Diagnosis of piriformis syndrome is difficult and its precise definition is
      highly controversial. In this article, the authors present the case of a patient
      who had clinical features suggestive of piriformis syndrome. During surgery the
      patient was found to have a rare variation in anatomical structures, in which the
      peroneal nerve was displaced by the piriformis muscle. Surgical decompression did
      not alleviate the patient's symptoms.

PMID- 11302671
TI  - Dynamic and three-dimensional transcranial ultrasonography of an arachnoid cyst
      in the cerebral convexity. Technical note.
AB  - Structural imaging of the brain, such as cerebral computerized tomography (CT)
      and magnetic resonance (MR) imaging, is state-of-the-art. Dynamic transcranial
      (dTC) ultrasonography and three-dimensional (3D) transcranial color-coded duplex
      (TCC) ultrasonography are complementary, noninvasive procedures with the capacity
      for real-time imaging, which may aid in the temporary management of space
      occupying lesions. A 16-year-old woman presented with recurrent tension-type
      headaches. A space-occupying arachnoid cyst in the cerebral convexity was
      demonstrated on MR images. The patient underwent an examination for raised
      intracranial pressure. which was performed using a standard color-coded duplex
      ultrasonography system attached to a personal computer-based system for 3D data
      acquisition. Transcranial ultrasonography was used to identify the outer
      arachnoid membrane of the cyst, which undulated freely in response to rotation of
      the patient's head (headshake maneuver). Three-dimensional data sets were
      acquired and, using a multiplanar reformatting reconstruction algorithm, the
      authors obtained high-resolution images that corresponded to the initial MR image
      and a follow-up cranial CT scan. No detectable differences were observed on dTC
      or 3D TC ultrasonograms obtained at follow-up examinations performed 9 and 28
      months later. Three-dimensional TCC and dTC ultrasonography may complement
      conventional diagnostic procedures such as MR and CT imaging. This report
      represents evidence of the high resolution and good reproducibility of 3D TC
      methods. Ultrasonography is a mobile and inexpensive tool and may be used to
      improve management and therapeutic strategies for patients with space-occupying
      brain lesions in selected cases.

PMID- 11302672
TI  - Transcrusal approach to the petroclival region with hearing preservation.
      Technical note and illustrative cases.
AB  - As a term, the "petrosal approach" to the petroclival region has a variety of
      meanings. The authors define a common nomenclature based on historical
      contributions and add new terminology to describe a technique of hearing
      preservation that allows for greater exposure of the petroclival region. The
      degree of temporal bone dissection defines five stages of operation. The authors
      used the second or "transcrusal" stage, in which the posterior and superior
      semicircular canals are sacrificed while preserving hearing, in six consecutive
      cases. Use of a common terminology ensures better understanding among surgeons.
      In the authors' hands, hearing has been successfully preserved in six patients
      after partial labyrinthectomy.

PMID- 11302673
TI  - Cosmetic and functional reconstruction achieved using a split myofascial bone
      flap for pterional craniotomy. Technical note.
AB  - Cosmetic deformities that appear following pterional craniotomy are usually
      caused by temporal muscle atrophy, injury to the frontotemporal branch of the
      facial nerve, or bone pits in the craniotomy line. To resolve these problems
      during pterional craniotomy, an alternative method was developed in which a split
      myofascial bone flap and a free bone flap are used. The authors have used this
      method in the treatment of 40 patients over the last 3 years. Excellent cosmetic
      and functional results have been obtained. This method can provide wide exposure
      similar to that achieved using Yasargil's interfascial pterional craniotomy,
      without limiting the operative field with a bulky temporal muscle flap.

PMID- 11302674
TI  - Multiple-revolution spiral osteotomy for cranial reconstruction. Technical note.
AB  - Various combinations of cranial remodeling techniques are used in an attempt to
      provide optimal cosmetic results and to reduce possible sequelae associated with
      craniosynostosis. One element of deformity that is difficult to correct directly
      is an overly flattened area such as that found in the parietal area in sagittal
      synostosis, unilaterally in lambdoid synostosis, or even in severe positional
      molding. The authors present a novel application for recontouring cranial bone,
      namely the multiple-revolution spiral osteotomy. The advantages of this technique
      include the avoidance of large areas of craniectomy and immediate correction of
      the cranial deformity. The surgical procedure, illustrative cases, early results,
      and apparent benefits of this technique are discussed.

PMID- 11302675
TI  - Peritoneal shunt tube placement performed using an endoscopic threaded imaging
      port. Technical note.
AB  - The authors used an endoscopic threaded imaging port that originally was
      developed for laparoscopy to access the peritoneal cavity, and applied this
      device to the placement of a peritoneal shunt tube in patients suffering from
      hydrocephalus. Using this system, the peritoneum can be opened quickly under
      direct vision by using an endoscope through a small skin incision. The peritoneal
      cavity is secured by replacing the cannula with a polyvinyl chloride (PVC) tube.
      At the end of surgery, the terminal end of the shunt tube is inserted through the
      PVC tube, which serves as a guiding catheter. Only one or two skin stitches are
      needed for closure. This method has proved to be safe, quick, and less invasive
      than conventional minilaparotomy.

PMID- 11302676
TI  - Spontaneous thrombosis of a giant aneurysm following pregnancy. Case
      illustration.

PMID- 11302677
TI  - Cranial fasciitis. Case illustration.

PMID- 11302678
TI  - Bone marrow transplantation.

PMID- 11302679
TI  - Pulsatility index.

PMID- 11302680
TI  - Landmarks for the transverse sinus and torcular herophili.

PMID- 11302682
TI  - Ultrasonography.

PMID- 11302681
TI  - Motor cortex stimulation.

PMID- 11302683
TI  - The melanoma antigen genes--any clues to their functions in normal tissues?
AB  - The melanoma antigen (MAGE) genes were initially isolated from melanomas and
      turned out to have an almost exclusively tumor-specific expression pattern. This
      led to the idea of using MAGE genes as targets for cancer immunotherapy, and MAGE
      peptides are currently being investigated as immunizing agents in clinical
      studies. Although 23 human and 12 mouse MAGE genes have been isolated in various
      tumors and characterized, not much is known about their function in normal cells.
      In adult tissues, most MAGE genes are expressed only in the testis and expression
      patterns suggest that this gene family is involved in germ cell development. In
      contrast to the MAGE genes, more functional data have accumulated around the MAGE
      related gene necdin. This gene encodes a neuron-specific growth suppressor that
      facilitates the entry of the cell into cell cycle arrest. Necdin is functionally
      similar to the retinoblastoma protein and binds to and represses the activity of
      cell-cycle-promoting proteins such as SV40 large T, adenovirus E1A, and the
      transcription factor E2F. Necdin also interacts with p53 and works in an additive
      manner to inhibit cell growth. In this review we will focus on the normal
      functions of MAGE genes and we speculate, based on the patterns of MAGE
      expression and on observed functions of necdin, that this gene family is involved
      in cell cycle regulation, especially during germ cell development.

PMID- 11302684
TI  - Histone acetylation and chromatin remodeling.
AB  - Chromatin represents a repressive barrier to the process of transcription. This
      molecular obstacle is a highly dynamic structure, able to compact the DNA of the
      entire genome into the confines of a nucleus, and yet it allows access to the
      genetic information held within. The acetylation of histones has emerged as a
      regulatory mechanism capable of modulating the properties of chromatin and thus
      the competence of the DNA template for transcriptional activation. The role of
      acetylation in chromatin remodeling is therefore of paramount importance to our
      understanding of gene regulation in vivo.

PMID- 11302685
TI  - Early shifts in gene expression during chondroinduction of human dermal
      fibroblasts.
AB  - Treatment options for damaged articular cartilage are limited because of that
      tissue's poor capacity for repair. Possible approaches to this problem are to
      stimulate cartilage matrix production in situ or to engineer replacement tissue.
      Both of these approaches would benefit from a detailed understanding of the
      molecular mechanisms of chondroblast differentiation. In previous studies, we
      described a novel in vitro model of postnatal chondroblast differentiation. That
      model of induced chondrogenesis was used to test the hypothesis that cellular
      interactions with demineralized bone powder (DBP) would induce specific, early
      shifts in gene expression, prior to the expression of cartilage matrix genes.
      Differentially expressed genes were identified by representational difference
      analysis of human dermal fibroblasts cultured for 3 days with DBP in three
      dimensional collagen sponges. Genes that were upregulated by DBP comprised
      several functional classes, including cytoskeletal elements, protein synthesis
      and trafficking, and transcriptional regulation. Kinetic analysis of gene
      expression over 21 days showed that vigilin was transiently upregulated on day 3.
      In contrast, expression of cartilage signature genes continued to increase. These
      results are an important step toward complete characterization of the mechanisms
      by which DBP induces chondroblastic differentiation in postnatal cells.

PMID- 11302686
TI  - Purification of mouse primary myoblasts based on alpha 7 integrin expression.
AB  - Fundamental insights have come from the study of myogenesis. Primary myoblasts
      isolated directly from muscle tissue more closely approximate myogenesis than
      established cell lines. However, contamination of primary muscle cultures with
      nonmyogenic cells can complicate the results. To overcome this problem, we
      previously described a method for myoblast purification based on novel culture
      conditions (T. A. Rando and H. M. Blau, 1994, J. Cell Biol. 125, 1275--1287).
      Here we report a refinement of this method that leads directly to an enriched
      population of mouse primary myoblasts, within significantly fewer population
      doublings. The method described here avoids using adhesion as a criterion for
      selection. This advance capitalizes on the ability of the antibody CA5.5 to
      recognize alpha 7 integrin, a muscle-specific cell surface antigen. Enrichment of
      myoblasts to greater than 95% of the cell population can be achieved by a single
      round of flow cytometry or magnetic bead separation. This is the first
      description of a mouse myoblast purification method based on a cell-type-specific
      antigen. The ease of this procedure for isolating primary myoblasts should expand
      the opportunities for (1) using these cells in cell transplantation studies in
      animal models of human disease, (2) isolating and characterizing mutant myoblasts
      from transgenic animals, and (3) allowing in vitro studies of molecules that
      regulate muscle cell growth, differentiation, and neoplasia.

PMID- 11302687
TI  - Cell cycle regulation of NF-kappa b-binding activity in cells from human
      glioblastomas.
AB  - Glioblastoma multiforme is a highly malignant and anaplastic tumor of the central
      nervous system representing more than 50% of all malignant gliomas. The cell
      origin of this highly undifferentiated tumor remains obscure, although it is
      postulated that glioblastomas are developed from astrocytes. The rapid growth of
      the glioma and the state of its undifferentiation are attributed to the
      deregulation of several signal transduction pathways and cell cycle events.
      Recent studies showed diverse functions for the NF-kappa B/Rel family of
      inducible transcription factors including differentiation, apoptosis,
      oncogenesis, and cell cycle regulation. We sought to examine the level of NF
      kappa B activity throughout the glioma's cell cycle. Results from band-shift
      studies indicated a biphasic NF-kappa B DNA-binding activity in the nuclei of
      cycling glioblastoma cells. We showed that NF-kappa B-binding activity maximizes
      in nuclear extracts at specific cell cycle stages including G0/G1, mid-late G1,
      and S phase. Results from Northern blotting studies revealed that the
      differential expression of the NF-kappa B subunits, p50 and p65, may not be
      responsible for cell cycle stage-specific association of NF-kappa B subunits with
      DNA. However, results from Western blotting analysis utilizing nuclear extracts
      from glioma cells throughout the cell cycle demonstrated that the nuclear
      accumulation of p50 and p65 perfectly correlates with their DNA-binding activity.
      These observations suggest that the nuclear translocation of the p50/p65 subunit
      of NF-kappa B in glioma cells is cell cycle stage-dependent and that is distinct
      from the differential mRNA expression of these genes during glioma cell cycling.
      The possible role of NF-kappa B in glioma cell formation and regulation of
      cellular genes by NF-kappa B in these tumor cells is discussed.

PMID- 11302688
TI  - Inhibition of cell proliferation by the PCNA-binding region of p21 expressed as a
      GFP miniprotein.
AB  - p21 (WAF1/Cip1) is the only member of the CIP/KIP family which has a well
      characterized PCNA-binding domain. p21 is known to have an important function in
      the coordination of the cellular pathways which are activated in response to DNA
      damage, though the significance of the p21-PCNA interaction is not completely
      clear. We have analyzed the effects of expressing a miniprotein containing the
      PCNA-binding domain of p21 upon the cell cycle and upon the proliferation of
      various cell types. We have compared this with the effect of expressing a mutant
      form which is defective in PCNA-binding, but which retains the secondary cyclin
      CDK-inhibitory site. No PCNA-dependent effects were seen in the short term upon
      cell cycle distribution. However, clonogenic assays show that the GFP-peptide
      miniprotein can significantly suppress proliferation in a PCNA-dependent manner.
      In some cell types, however, the suppression of proliferation was not PCNA
      dependent, suggesting that cellular environment is a contributory factor to the
      effect of this miniprotein. The capacity of this peptide sequence to suppress
      cell proliferation in vivo is of interest as the basis for the design of
      potential antiproliferative therapeutic agents.

PMID- 11302689
TI  - Use of peptides from p21 (Waf1/Cip1) to investigate PCNA function in Xenopus egg
      extracts.
AB  - Cell-free systems derived from unfertilized Xenopus eggs have been particularly
      informative in the study of the regulation and biochemistry of DNA replication.
      We have developed a Xenopus-based system to analyze proliferating cell nuclear
      antigen (PCNA)-specific effects on the functional properties of egg extracts. To
      do this, we have coupled peptides derived from p21 (Waf1/Cip1) to beads and used
      these to deplete PCNA from Xenopus egg extracts. The effect on various aspects of
      DNA replication can be analyzed after the readdition of PCNA and other purified
      proteins. Using this system, we have shown that replication of single-stranded
      M13 DNA is entirely dependent upon PCNA. By adding exogenous T7 DNA polymerase to
      PCNA-depleted extracts, we have uncoupled processive DNA replication from PCNA
      activity and so created an experimental system to analyze the dependence of
      postreplicative processes on PCNA function. We have shown that successful
      chromatin assembly is specifically dependent on PCNA. However, systems for
      analyzing the far more complex mechanisms required for the replication of nuclear
      double-stranded DNA have proved so far to be refractory to specific PCNA
      depletion.

PMID- 11302690
TI  - Nuclear gems and Cajal (coiled) bodies in fetal tissues: nucleolar distribution
      of the spinal muscular atrophy protein, SMN.
AB  - SMN, the affected protein in spinal muscular atrophy (SMA), is a cytoplasmic
      protein that also occurs in nuclear structures called "gems" and is involved in
      snRNP maturation. Coilin-p80 is a marker protein for nuclear Cajal bodies (coiled
      bodies; CBs) which are also involved in snRNP maturation, storage or transport.
      We now show that gems and CBs are present in all fetal tissues, even those that
      lack gems/CBs in the adult. Most gems and CBs occur as separate nuclear
      structures in fetal tissues, but their colocalization increases with fetal age
      and is almost complete in the adult. In adult tissues, up to half of all gems/CBs
      are inside the nucleolus, whereas in cultured cells they are almost exclusively
      nucleoplasmic. The nucleolar SMN is often more diffusely distributed, compared
      with nucleoplasmic gems. Up to 30% of cells in fetal tissues have SMN distributed
      throughout the nucleolus, instead of forming gems in the nucleoplasm. The results
      suggest a function for gems distinct from Cajal bodies in fetal nuclei and a
      nucleolar function for SMN. Spinal cord, the affected tissue in SMA, behaves
      differently in several respects. In both fetal and adult motor neurons, many
      gems/CBs occur as larger bodies closely associated with the nucleolar perimeter.
      Uniquely in motor neurons, gems/CBs are more numerous in adult than in fetal
      stages and colocalization of gems and CBs occurs earlier in development. These
      unusual features of motor neurons may relate to their special sensitivity to
      reduced SMN levels in SMA patients.

PMID- 11302691
TI  - Mammalian prohibitin proteins respond to mitochondrial stress and decrease during
      cellular senescence.
AB  - The two prohibitin proteins, Phb1p and Phb2p(BAP37), have been ascribed various
      functions, including cell cycle regulation, apoptosis, assembly of mitochondrial
      respiratory chain enzymes, and aging. We show that the mammalian prohibitins are
      present in the inner mitochondrial membrane and are always bound to each other,
      with no free protein detectable. They are coexpressed during development and in
      adult mammalian tissues, and expression levels are indicative of a role in
      mitochondrial metabolism, but are not compatible with roles in the regulation of
      cellular proliferation or apoptosis. High level expression of the proteins is
      consistently seen in primary human tumors, while cellular senescence of human and
      chick fibroblasts is accompanied by heterogeneous decreases in both proteins. The
      two proteins are induced by metabolic stress caused by an imbalance in the
      synthesis of mitochondrial- and nuclear-encoded mitochondrial proteins, but do
      not respond to oxidative stress, heat shock, or other cellular stresses. The gene
      promoter sequences contain binding sites for the Myc oncoprotein and
      overexpression of Myc induces expression of the prohibitins. The data support
      conserved roles for the prohibitins in regulating mitochondrial respiratory
      activity and in aging.

PMID- 11302692
TI  - Inhibition of nitric-oxide-mediated apoptosis in Jurkat leukemia cells despite
      cytochrome c release.
AB  - We have recently shown that nitric-oxide (NO)-induced apoptosis in Jurkat human
      leukemia cells requires degradation of mitochondria phospholipid cardiolipin,
      cytochrome c release, and activation of caspase-9 and caspase-3. Moreover, an
      inhibitor of lipid peroxidation, Trolox, suppressed apoptosis in Jurkat cells
      induced by NO donor glycerol trinitrate. Here we demonstrate that this
      antiapoptotic effect of Trolox occurred despite massive release of the
      mitochondrial protein cytochrome c into the cytosol and mitochondrial damage.
      Incubation with Trolox caused a profound reduction of intracellular ATP
      concentration in Jurkat cells treated by NO. Trolox prevented cardiolipin
      degradation and caused its accumulation in Jurkat cells. Furthermore, Trolox
      markedly downregulated the NO-mediated activation of caspase-9 and caspase-3.
      Caspase-9 is known to be activated by released cytochrome c and together with
      caspase-3 is considered the most proximal to mitochondria. Our results suggest
      that the targets of the antiapoptotic effect of Trolox are located downstream of
      the mitochondria and that caspase activation and subsequent apoptosis could be
      blocked even in the presence of cytochrome c released from the mitochondria.

PMID- 11302693
TI  - Heterochromatin is not an adequate explanation for close proximity of interphase
      chromosomes 1--Y, 9--Y, and 16--Y in human spermatozoa.
AB  - Analysis of human spermatozoa and lymphocytes using C-banding techniques and in
      situ hybridization has shown a higher order packaging of the human genome.
      Chromosomes are not distributed entirely at random within the nucleus. In
      particular, chromosomes 1, 9, and 16, carrying large blocks of pericentromeric
      heterochromatin, and the Y chromosome, carrying heterochromatin in Yq12, are in
      close proximity to each other within the nucleus and are involved in somatic
      pairing with nonhomologous chromosomes. In order to determine whether the close
      proximity of these chromosomes in any way is attributable to the distribution of
      heterochromatin, double in situ hybridization was performed on chromosomes 1--Y,
      9--Y, and 16--Y as well as on 1--X, 9--X, and 16--X-with chromosome X as the
      other gonosome carrying less heterochromatin-in human spermatozoa. Each pair was
      found to have a nonrandom spatial distribution. However, comparison of the
      arrangement of chromosomes 1--Y versus 1--X and 9--Y versus 9--X revealed that
      heterochromatin cannot be the only cause for the tendency of chromosome fusion,
      because only the results of the chromosome pair 1--Y/1--X could support this
      proposition. In conclusion, the heterochromatin effect cannot be, in itself, an
      adequate explanation for chromosome association, implicating as well other
      mechanisms.

PMID- 11302694
TI  - Peptide-based targeting of fluorophores to organelles in living cells.
AB  - Peptides carrying organelle-specific import or retention sequences can target the
      fluorophore BODIPY(581/591) to the nucleus, peroxisomes, endoplasmic reticulum
      (ER), or the trans-Golgi network (TGN). The peroxisomal peptide contains the PTS1
      sequence AKL. For targeting to the ER or TGN, the peptides carry the retention
      sequences KDEL and SDYQRL, respectively. A peptide carrying the nuclear leader
      sequence of the simian virus SV40 large tumor antigen, KKKRK, was used to direct
      the fluorophore to the nucleus. The fluorescent peptides for peroxisomes, ER, and
      the TGN spontaneously incorporate into living fibroblasts at 37 degrees C and
      accumulate in their target organelles within minutes. The uptake is still
      significant at 4 degrees C, indicating that endocytosis is not required for
      internalization. The highly charged nuclear peptide (net charge +4) does not
      spontaneously internalize. However, by transient permeabilization of the plasma
      membrane, this fluorescent peptide was found to rapidly accumulate in the
      nucleus. These fluorescent peptides open new opportunities to follow various
      aspects of specific organelles such as their morphology, biogenesis, dynamics,
      degradation, and their internal parameters (pH, redox).

PMID- 11302695
TI  - Uncoupling the senescent phenotype from telomere shortening in hydrogen peroxide
      treated fibroblasts.
AB  - Normal human cells have a limited replicative potential and inevitably reach
      replicative senescence in culture. Replicatively senescent cells show multiple
      molecular changes, some of which are related to the irreversible growth arrest in
      culture, whereas others resemble the changes occurring during the process of
      aging in vivo. Telomeres shorten as a result of cell replication and are thought
      to serve as a replicometer for senescence. Recent studies show that young cells
      can be induced to develop features of senescence prematurely by damaging agents,
      chromatin remodeling, and overexpression of ras or the E2F1 gene. Accelerated
      telomere shortening is thought to be a mechanism of premature senescence in some
      models. In this work, we test whether the acquisition of a senescent phenotype
      after mild-dose hydrogen peroxide (H(2)O(2)) exposure requires telomere
      shortening. Treating young HDFs with 150 microM H(2)O(2) once or 75 microM
      H(2)O(2) twice in 2 weeks causes long-term growth arrest, an enlarged morphology,
      activation of senescence-associated beta-galactosidase, and elevated expression
      of collagenase and clusterin mRNAs. No significant telomere shortening was
      observed with H(2)O(2) at doses ranging from 50 to 200 microM. Weekly treatment
      with 75 microM H(2)O(2) also failed to induce significant telomere shortening.
      Failure of telomere shortening correlated with an inability to elevate p16
      protein or mRNA in H(2)O(2)-treated cells. In contrast, p21 mRNA was elevated
      over 40-fold and remained at this level for at least 2 weeks after a pulse
      treatment of H(2)O(2). The role of cell cycle checkpoints centered on p21 in
      premature senescence induced by H(2)O(2) is discussed here.

PMID- 11302696
TI  - Transient expression of wild-type or biologically inactive telomerase allows the
      formation of artificial telomeres in mortal human cells.
AB  - Telomere seeding, the formation of artificial telomeres, has been routinely
      successful in immortalized but not normal human cells. We compared seeding
      efficiencies in preimmortal and immortal SV40-transformed cells using plasmid
      telomeres with T(2)AG(3) tracts of 1600 and 3200 bp. Seeding occurred only in
      immortal cells, indicating that transformed preimmortal cells behave like normal
      cells vis a vis formation of new telomeres and that T-antigen inhibition of
      cellular checkpoints is insufficient to allow seeding. Telomerase is active in
      immortal but not preimmortal cells, which do not express the reverse
      transcriptase hTERT. Upon transient expression of hTERT, seeds with 1600 bp of
      T(2)AG(3) formed telomeres in preimmortal cells. Comparable seeding efficiencies
      were obtained with wild-type hTERT or the HA-tagged protein that is catalytically
      active but unable to maintain endogenous telomeres. No seeding occurred with
      catalytically inactive hTERT. Given that telomerase expression was transient and
      that longer seeds did not form telomeres in the absence of the enzyme, seeding
      may not be elicited merely by elongation of telomeric sequences. We propose that
      modification of the telomeric terminus by telomerase may contribute to telomere
      seeding by leading to formation of a structure that impedes rejoining of this
      terminus with chromosomal sequences.

PMID- 11302697
TI  - Specific blockade by CD54 and MHC II of CD40-mediated signaling for B cell
      proliferation and survival.
AB  - Regulation of B lymphocyte proliferation is critical to maintenance of self
      tolerance, and intercellular interactions are likely to signal such regulation.
      Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC
      II with CD40 inhibited cell cycle progression and promoted apoptosis of mouse
      splenic B cells. This resulted from specific blockade of NF-kappa B induction,
      which normally inhibits apoptosis. LPS- or B cell receptor (BCR)-induced
      proliferation was not inhibited by these treatments, and mAb-induced association
      of CD40 with other B cell surface molecules did not have these effects. Addition
      of BCR or IL-4 signals did not overcome the effect of ICAM-1 or MHC II on CD40
      induced proliferation. FasL expression was not detected in B cell populations.
      These results show that MHC II and ICAM-1 specifically modulate CD40-mediated
      signaling, so inhibiting proliferation and preventing inhibition of apoptosis.

PMID- 11302698
TI  - Glucocorticoid hormone-induced receptor localization to the chromatin fibers
      formed on injected DNA in Xenopus oocytes.
AB  - Oocytes from Xenopus laevis have provided a model system for studying the dynamic
      changes that occur in chromatin during gene activation. We have reconstituted
      glucocorticoid receptor (GR) induced transcription from the mouse mammary tumor
      virus (MMTV) promoter by intranuclear injection of an MMTV-driven reporter and
      cytoplasmic injection of synthetic mRNA(GR) into Xenopus oocytes. Here we
      investigate the intranuclear distribution of injected DNA, which is assembled
      into chromatin. We show that this chromatin is organized as an intranuclear
      fibrous network. Unliganded GR is located in the cytosol and hormone triggers its
      nuclear translocation and association with the chromatin fibers. Furthermore, we
      analyze the intranuclear distribution of other factors involved in transcription
      from the MMTV promoter. Indirect immunofluorescence microscopy on cryostat
      sectioned oocytes revealed that BRG1, which is a subunit of the SWI/SNF chromatin
      remodeling complex, as well as RNA polymerase II and recombinantly expressed
      Xenopus nuclear factor 1-B, are all associated with the endogenous chromosomes
      and the chromatin fibers formed on injected DNA. This association does not depend
      on specific DNA binding sites and appears to be nonspecific.

PMID- 11302699
TI  - FYVE-DSP2, a FYVE domain-containing dual specificity protein phosphatase that
      dephosphorylates phosphotidylinositol 3-phosphate.
AB  - We have recently isolated FYVE-DSP1, a FYVE domain-containing dual specificity
      protein phosphatase (R. Zhao, Y. Qi, and Z. J. Zhao, Biochem. Biophys. Res.
      Commun. 270, 222--229 (2000)). Here, we report a novel isozyme that we designated
      FYVE-DSP2. FYVE-2 contains a single FYVE domain at the C-terminus, and it shares
      approximately 47% overall sequence identity with FYBE-DSP1. Genomic sequence
      analyses revealed that the FYVE-DSP1 and FYVE-DSP2 genes share similar
      intron/exon organization. They are localizedon human chromosome 22q12 and
      chromosome 17, respectively. Like FYVE-DSP1, recombinant FYVE-DSP2
      dephosphorylated low-molecular-weight phosphatase substrate para
      nitrophenylphosphate, and its activity was inhibited by sodium vanadate. More
      importantly, our study also revealed that both FYVE-DSP1 and FYVE-DSP2
      efficiently and specifically dephosphorylated phosphotidylinositol 3-phosphate.
      Subcellular fractionation demonstrated partition of FYVE-DSP1 and FYVE-DSP2 in
      membrane fractions, and immunofluorescent cell staining showed perinuclear
      localization of the enzymes. FYVE-DSP2 is expressed in many human tissues with an
      alternatively spliced isoform expressed in the kidney. Together with two
      homologous hypothetical proteins found in Caenorhabditis elegans and Drosophila,
      FYVE-DSP1 and FYVE-DSP2 form a subfamilyof phosphatases that may have an
      importantrole in cellular processes.

PMID- 11302700
TI  - Increased mitochondrial-encoded gene transcription in immortal DF-1 cells.
AB  - We have established, in continuous cell culture, a spontaneously immortalized
      chicken embryo fibroblast (CEF) cell line (DF-1) as well as several other
      immortal CEF cell lines. The immortal DF-1 cells divided more rapidly than
      primary and other immortal CEF cells. To identify the genes involved in rapidly
      dividing DF-1 cells, we have used differential display RT-PCR. Of the numerous
      genes analyzed, three mitochondrial-encoded genes (ATPase 8/6, 16S rRNA, and
      cytochrome b) were shown to express at higher levels in DF-1 cells compared to
      primary and other immortal CEF cells. The inhibition of mitochondrial translation
      by treatment with chloramphenicol markedly decreased ATP production and cell
      proliferation in DF-1 cells, while not affecting growth in either primary or
      other immortal CEF cells. This result suggests a correlation between rapid cell
      proliferation and the increased mitochondrial respiratory functions. We also
      determined that the increased transcription of mitochondrial-encoded genes in DF
      1 cells is due to increased de novo transcript synthesis as shown by
      mitochondrial run-on assays, and not the result of either increased mitochondrial
      biogenesis or mitochondrial transcript half-lives. Together, the present studies
      suggest that the transcriptional activation of mitochondrial-encoded genes and
      the elevated respiratory function should be one of the characteristics of rapidly
      dividing immortal cells.

PMID- 11302701
TI  - Oligomeric structure of alpha-calmodulin-dependent protein kinase II.
AB  - The subunit stoichiometry and symmetry of the neuronal alpha-calmodulin-dependent
      protein kinase II (alphaCaMKII) is investigated in this report to understand the
      structural basis of its regulation and mechanism at the molecular level. Two
      preparations are studied, alphaCaMKII obtained by overexpression in baculovirus
      transfected insect cells and CaMKII isolated from rat forebrain. The structures,
      are studied by electron microscopy and image analysis. Single-particle analysis
      of individual molecular images reveals a molecule with a circular outline and
      pronounced 6-fold rotational symmetry of the central part. The central part has
      an outer radius of approximately 6 nm and is composed of six lobes grouped around
      a hollow centre. The outer ring extends to approximately 15 nm and consists of 12
      apparent domains. These data are interpreted in terms of a three-dimensional
      model of the alphaCaMKII complex consisting of 12 subunits, each corresponding to
      a single alphaCaMKII polypeptide chain. The inner ring corresponding to
      approximately one-third of the molecular mass of the complex is made up of the C
      terminal association domains. The 12 association domains are arranged in two
      concentric hexagonal rings at different axial levels and in rotational register.
      The outer ring corresponding to the remaining molecular mass of the complex is
      made up of the 12 N-terminal catalytic domains located at an axial level halfway
      between the two levels of the association domains. The 6-fold symmetry of stacked
      association domains may derive from subunit arrangements corresponding to either
      the C6 or the D6 point group symmetries. The symmetry and the resulting subunit
      arrangement define the pattern and extent of regulatory autophosphorylation
      within the alphaCaMKII complex.

PMID- 11302702
TI  - The solution structure of bacteriophage lambda protein W, a small morphogenetic
      protein possessing a novel fold.
AB  - Protein W (gpW) from bacteriophage lambda is required for the stabilization of
      DNA within the phage head and for attachment of tails onto the head during
      morphogenesis. Although comprised of only 68 residues, it likely interacts with
      at least two other proteins in the mature phage and with DNA. Thus, gpW is an
      intriguing subject for detailed structural studies. We have determined its
      solution structure using NMR spectroscopy and have found it to possesses a novel
      fold consisting of two alpha-helices and a single two-stranded beta-sheet
      arranged around a well-packed hydrophobic core. The 14 C-terminal residues of
      gpW, which are essential for function, are unstructured in solution.

PMID- 11302703
TI  - The crystal structures of psoralen cross-linked DNAs: drug-dependent formation of
      Holliday junctions.
AB  - The single-crystal structures are presented for two DNA sequences with the
      thymine bases covalently cross-linked across the complementary strands by 4'
      hydroxymethyl-4,5',8-trimethylpsoralen (HMT). The HMT-adduct of d(CCGCTAGCGG)
      forms a psoralen-induced Holliday junction, showing for the first time the effect
      of this important class of chemotheraputics on the structure of the recombination
      intermediate. In contrast, HMT-d(CCGGTACCGG) forms a sequence-dependent junction.
      In both structures, the DNA duplex is highly distorted at the thymine base linked
      to the six-member pyrone ring of the drug. The psoralen cross-link defines the
      intramolecular interactions of the drug-induced junction, while the sequence
      dependent structure is nearly identical to the native Holliday junction of
      d(CCGGTACCGG) alone. The two structures contrast the effects of drug- and
      sequence-dependent interactions on the structure of a Holliday junction,
      suggesting a role for psoralen in the mechanism to initiate repair of psoralen
      lesions in mammalian DNA.

PMID- 11302705
TI  - Positively charged residues at the N-terminal arm of the homeodomain are required
      for efficient DNA binding by homeodomain-leucine zipper proteins.
AB  - Plant homeodomain-leucine zipper proteins, unlike most animal homeodomains, bind
      DNA efficiently only as dimers. In the present work, we report that the deletion
      of the homeodomain N-terminal arm (first nine residues) of the homeodomain
      leucine zipper protein Hahb-4 dramatically affects its DNA-binding affinity,
      causing a 70-fold increase in dissociation constant. The addition of the N
      terminal arm of Drosophila Antennapedia to the truncated form restores the DNA
      binding affinity of dimers to values similar to those of the native form.
      However, the Antennapedia N-terminal arm is not able to confer increased binding
      affinity to monomers of Hahb-4 lacking the leucine zipper motif, indicating that
      the inefficient binding of monomers must be due to structural differences in
      other parts of the molecule. The construction of proteins with modifications at
      residues 5 to 7 of the homeodomain suggests strongly that positively charged
      amino acids at these positions play essential roles in determining the DNA
      binding affinity. However, the effect of mutations at positions 6 and 7 can be
      counteracted by introducing a stretch of positively charged residues at positions
      1 to 3 of the homeodomain. Sequence comparisons indicate that all homeodomain
      leucine zipper proteins might use contacts of the N-terminal arm with DNA for
      efficient binding. The occurrence of a homeodomain with a DNA-interacting N
      terminal arm must then be an ancient acquisition in evolution, earlier than the
      separation of lines leading to metazoa, fungi and plants.

PMID- 11302704
TI  - Homo-oligomerisation and nuclear localisation of mouse histone deacetylase 1.
AB  - Reversible histone acetylation changes the chromatin structure and can modulate
      gene transcription. Mammalian histone deacetylase 1 (HDAC1) is a nuclear protein
      that belongs to a growing family of evolutionarily conserved enzymes catalysing
      the removal of acetyl residues from core histones and other proteins. Previously,
      we have identified murine HDAC1 as a growth factor-inducible protein in murine T
      cells. Here, we characterise the molecular function of mouse HDAC1 in more
      detail. Co-immunoprecipitation experiments with epitope-tagged HDAC1 protein
      reveal the association with endogenous HDAC1 enzyme. We show that HDAC1 can homo
      oligomerise and that this interaction is dependent on the N-terminal HDAC
      association domain of the protein. Furthermore, the same HDAC1 domain is also
      necessary for in vitro binding of HDAC2 and HDAC3, association with RbAp48 and
      for catalytic activity of the enzyme. A lysine-rich sequence within the carboxy
      terminus of HDAC1 is crucial for nuclear localisation of the enzyme. We identify
      a C-terminal nuclear localisation domain, which is sufficient for the transport
      of HDAC1 and of reporter fusion proteins into the nucleus. Alternatively, HDAC1
      can be shuttled into the nucleus by association with another HDAC1 molecule via
      its N-terminal HDAC association domain. Our results define two domains, which are
      essential for the oligomerisation and nuclear localisation of mouse HDAC1.

PMID- 11302706
TI  - Stoichiometry of the Sm proteins in yeast spliceosomal snRNPs supports the
      heptamer ring model of the core domain.
AB  - Seven Sm proteins (B/B', D1, D2, D3, E, F and G proteins) containing a common
      sequence motif form a globular core domain within the U1, U2, U5 and U4/U6
      spliceosomal snRNPs. Based on the crystal structure of two Sm protein dimers we
      have previously proposed a model of the snRNP core domain consisting of a ring of
      seven Sm proteins. This model postulates that there is only a single copy of each
      Sm protein in the core domain. In order to test this model we have determined the
      stoichiometry of the Sm proteins in yeast spliceosomal snRNPs. We have
      constructed seven different yeast strains each of which produces one of the Sm
      proteins tagged with a calmodulin-binding peptide (CBP). Further, each of these
      strains was transformed with one of seven different plasmids coding for one of
      the seven Sm proteins tagged with protein A. When one Sm protein is expressed as
      a CBP-tagged protein from the chromosome and a second protein was produced with a
      protein A-tag from the plasmid, the protein A-tag was detected strongly in the
      fraction bound to calmodulin beads, demonstrating that two different tagged Sm
      proteins can be assembled into functional snRNPs. In contrast when the CBP and
      protein A-tagged forms of the same Sm protein were co-expressed, no protein A-tag
      was detectable in the fraction bound to calmodulin. These results indicate that
      there is only a single copy of each Sm protein in the spliceosomal snRNP core
      domain and therefore strongly support the heptamer ring model of the spliceosomal
      snRNP core domain.

PMID- 11302707
TI  - Effects of chlorophyll a, chlorophyll b, and xanthophylls on the in vitro
      assembly kinetics of the major light-harvesting chlorophyll a/b complex, LHCIIb.
AB  - The major light-harvesting chlorophyll a/b complex (LHCIIb) of photosystem II in
      higher plants can be reconstituted with pigments in lipid-detergent micelles. The
      pigment-protein complexes formed are functional in that they perform efficient
      internal energy transfer from chlorophyll b to chlorophyll a. LHCIIb formation in
      vitro, can be monitored by the appearance of energy transfer from chlorophyll b
      to chlorophyll a in time-resolved fluorescence measurements. LHCIIb is found to
      form in two apparent kinetic steps with time constants of about 30 and 200
      seconds. Here we report on the dependence of the LHCIIb formation kinetics on the
      composition of the pigment mixture used in the reconstitution. Both kinetic steps
      slow down when the concentration of either chlorophylls or carotenoids is
      reduced. This suggests that the slower 200 seconds formation of functional LHCIIb
      still includes binding of both chlorophylls and carotenoids. LHCIIb formation is
      accelerated when the chlorophylls in the reconstitution mixture consist
      predominantly of chlorophyll a although the complexes formed are thermally less
      stable than those reconstituted with a chlorophyll a:b ratio < or = 1. This
      indicates that although chlorophyll a binding is more dominant in the observed
      rate of LHCIIb formation, the occupation of (some) chlorophyll binding sites with
      chlorophyll b is essential for complex stability. The accelerating effect of
      various carotenoids (lutein, zeaxanthin, violaxanthin, neoxanthin) on LHCIIb
      formation correlates with their affinity to two lutein-specific binding sites. We
      conclude that the occupation of these two carotenoid binding sites but not of the
      third (neoxanthin-specific) binding site is an essential step in the assembly of
      LHCIIb in vitro.

PMID- 11302708
TI  - Experimental assignment of the structure of the transition state for the
      association of barnase and barstar.
AB  - Association of a protein complex follows a two step reaction mechanism, with the
      first step being the formation of an encounter complex which evolves into the
      final complex. Here we present new experimental data for the association of the
      bacterial ribonuclease barnase and its polypeptide inhibitor barstar which shed
      light on the thermodynamics and structure of the transition state and preceding
      encounter complex of association at diminishing electrostatic attraction. We show
      that the activation entropy at the transition state is close to zero, with the
      activation enthalpy being equal to the free energy of binding. This observation
      was independent of the magnitude of the mutual electrostatic attraction, which
      were altered by mutagenesis or by addition of salt. The low activation entropy
      implies that the transition state is mostly solvated at all ionic strengths. The
      structure of the transition state was probed by measuring pairwise interaction
      energies using double-mutant-cycles. While at low ionic strength all proximal
      charge-pairs form contacts, at high salt only a subset of these interactions are
      maintained. More specifically, charge-charge interactions between partially
      buried residues are lost, while exposed charged residues maintain their ability
      to form specific interactions even at the highest salt concentration. Uncharged
      residues do not interact at any ionic strength. The results presented here
      suggest that the barnase-barstar binding sites are correctly aligned during the
      transition state even at diminishing electrostatic attraction, although specific
      short range interactions of uncharged residues are not yet formed. Furthermore,
      most of the interface desolvation (which contributes to the entropy of the
      system) has not yet occurred. This picture seems to be valid at low and high
      salt. However, at high salt, interactions of the activated complex are limited to
      a more restricted set of residues which are easier approached during diffusion,
      prior to final docking. This suggest that the steering region at high salt is
      more limited, albeit maintaining its specificity.

PMID- 11302709
TI  - The folding thermodynamics and kinetics of crambin using an all-atom Monte Carlo
      simulation.
AB  - We present a novel Monte Carlo simulation of protein folding, in which all heavy
      atoms are represented as interacting hard spheres. This model includes all
      degrees of freedom relevant to folding, all side-chain and backbone torsions, and
      uses a Go potential. In this study, we focus on the 46 residue alpha/beta protein
      crambin and two of its structural components, the helix and helix hairpin. For a
      wide range of temperatures, we recorded multiple folding events of these three
      structures from random coils to native conformations that differ by less than 1 A
      C(alpha) dRMS from their crystal structure coordinates. The thermodynamics and
      kinetic mechanism of the helix-coil transition obtained from our simulation shows
      excellent agreement with currently available experimental and molecular dynamics
      data. Based on insights obtained from folding its smaller structural components,
      a possible folding mechanism for crambin is proposed. We observed that the
      folding occurs via a cooperative, first order-like process, and that many folding
      pathways to the native state exist. One particular sequence of events constitutes
      a "fast-folding" pathway where kinetic traps are avoided. At very low
      temperatures, a kinetic trap arising from the incorrect packing of side-chains
      was observed. These results demonstrate that folding to the native state can be
      observed in a reasonable amount of time on desktop computers even when an all
      atom representation is used, provided the energetics sufficiently stabilize the
      native state.

PMID- 11302710
TI  - On Comparison Meaningfulness of Aggregation Functions.
AB  - This paper will give a description of all continuous functions which are
      comparison meaningful in the sense of measurement theory. Copyright 2001 Academic
      Press. 

PMID- 11302711
TI  - A Class of Probabilistic Unfolding Models for Polytomous Responses.
AB  - By revisiting the approaches used to present the Rasch model for polytomous
      response, this paper uses the principle of the rating formulation (Andrich, 1978)
      to construct a class of unfolding models for polytomous responses in terms of a
      set of latent dichotomous unfolding variables. By anchoring the dichotomous
      unfolding variables involved at the same location, this paper presents a
      formulation of a very general class of unfolding models for ordered polytomous
      responses, of which the unfolding models for ordered polytomous responses
      proposed hitherto are special cases. Within this class, the analytic and
      measurement properties of the probabilistic functions are well interpreted in
      terms of the latitudes of acceptance parameters of the dichotomous unfolding
      models. Based on the general form of this class of unfolding models, some new
      models are readily specified. Copyright 2001 Academic Press. 

PMID- 11302712
TI  - Probabilistic Multidimensional Scaling Using a City-Block Metric.
AB  - Using a probabilistic model, exact and approximate probability density functions
      (PDFs) for city-block distances and distance ratios are developed. The model
      assumes that stimuli can be represented by random vectors having multivariate
      normal distributions. Comparisons with the more common Euclidean PDFs are
      presented. The potential ability of the proposed model to correctly detect
      Euclidean and city-block metrics is briefly investigated. These results are then
      contrasted to those obtained using a deterministic, nonmetric model. Copyright
      2001 Academic Press. 

PMID- 11302713
TI  - Time Preference for Health: A Test of Stationarity versus Decreasing Timing
      Aversion.
AB  - This paper provides a new and more robust test of the descriptive validity of the
      constant rate discounted utility model in medical decision analysis. The constant
      rate discounted utility model is compared with two competing theories, Harvey's
      (1986) proportional discounting model and Loewenstein and Prelec's (1992)
      hyperbolic discounting model. To compare the various intertemporal models,
      previous studies on intertemporal preferences for health assumed a specific
      parametric form of the utility function for life-years and no discounting within
      the time periods that health states are experienced. The present study avoids
      such confounding assumptions by focusing on the axiomatic structure of the
      discounting models. The present study further differs by using choices instead of
      matching to elicit intertemporal preferences. The experimental results provide
      support for decreasing timing aversion, the condition underlying the proportional
      and the hyperbolic discounting model, but they violate stationarity, the central
      condition of the constant rate discounted utility model. There is some ambiguity
      whether the violations of stationarity are primarily caused by an immediacy
      effect. The results confirm violations of stationarity in choice-based
      elicitations tasks, in contrast with the results from Ahlbrecht and Weber (1997)
      which supported stationarity in choices over monetary outcomes. Copyright 2001
      Academic Press. 

PMID- 11302714
TI  - Independent Sampling vs Interitem Dependencies in Whole Report Processing:
      Contributions of Processing Architecture and Variable Attention.
AB  - All current models of visual whole report processing assume perceptual
      independence among the displayed items in which the perceptual processing of
      individual items is not affected by other items in the display. However, models
      proposed by Townsend (1981, Acta Psychologica 47, 149-173), Shibuya and Bundesen
      (1988, Journal of Experimental Psychology: Human Perception and Performance 14,
      591-600), and Bundesen (1990, Psychological Review 97, 523-547) contain
      postperceptual buffers that must predict negative dependencies. The perceptual
      independence assumption forms what we term the modal model class. A recent
      example of a model that assumes perceptual independence is the Independent
      Sampling Model of Loftus, Busey, and Senders (1993, Perception and Psychophysics
      54, 535-554). The fundamental independence assumption has only been directly
      tested once before, where tests revealed no dependencies except those produced by
      guessing. The present study tests the independence assumption using several
      different statistics and, contrary to most extant models of whole report, finds
      significant positive dependence. Poisson models do predict a positive dependence
      and we develop a succinctly parameterized version, the Weighted Path Poisson
      Model, which allows the finishing order to be a weighted probabilistic mechanism.
      However, it does not predict the data quite as well as a new model, the Variable
      Attention Model, which allows independence within trials (unlike the Poisson
      models). This model assumes that attention (or, potentially, other aspects such
      as signal quality) varies widely across trials, thus predicting an overall
      positive dependence. Intuitions for and against the competing models are
      discussed. In addition, we show, through mimicking formulae, that models which
      contain the proper qualitative type of dependence structure can be cast in either
      serial or parallel form. Copyright 2001 Academic Press. 

PMID- 11302715
TI  - Formal Requirements of Markov State Models for Paired Associate Learning.
AB  - Discrete state learning models that make Markov assumptions are a powerful tool
      for the analysis and optimization of performance in paired associate tasks. We
      seek here to derive bounds on the complexity needed by such models in order to
      account for the critical effects of lag and retention intervals on paired
      associate learning. More specifically, after establishing that two different
      Markov chains are needed (one for describing the effects of trials where a paired
      associate is presented and one for describing the effects of trials where the
      paired associate is not presented), we determine the minimum number of states
      required in a Markov model with two chains. It is shown formally that, under
      certain psychologically plausible assumptions, more than three states are
      required. A model with two chains and four states is presented and it is shown
      empirically that it can account for the lag and retention effects in paired
      associate learning. Copyright 2001 Academic Press. 

PMID- 11302716
TI  - Testing Evidence Accrual Models by Manipulating Stimulus Onset.
AB  - Many models of response time assume that subjects accrue stimulus "evidence"
      samples in time (e.g., random walk models, counter models). In this paper, the
      concept of one stimulus dominating another is used to construct a test of the
      whole class of evidence accrual models. For an example of dominance, consider
      stimuli that are presented either virtually instantaneously (stepped) or in a
      gradually increasing manner (ramped). Ramped stimuli are presented such that the
      ramped portion precedes the stepped onset of stepped stimuli. In this case ramped
      stimuli dominate stepped stimuli. In this paper the class of evidence accrual
      models is formalized. It is shown that under appropriate assumptions evidence
      accrual models do predict more accurate responses to dominating stimuli. However,
      this result does not hold for response latencies. There are anomalous cases where
      an evidence accrual model (the accumulator model of Vickers (1970, Ergonomics 13,
      37-58)) predicts slower mean correct response latencies to dominating stimuli. It
      is shown through extensive computer simulation that these anomalous cases occur
      only when response criteria are so asymmetric that there are exceedingly extreme
      response biases. For experiments where response biases are not exceedingly
      extreme, random walk and accumulator models predict more accurate and quicker
      correct responses to dominating stimuli. In sum, manipulating the time course of
      stimuli in accordance with the concept of dominance can provide empirical tests
      of the class of evidence accrual models. Copyright 2001 Academic Press. 

PMID- 11302717
TI  - Convergence of the Integration Dynamics of the Construction-Integration Model.
AB  - The connectionist network corresponding to the nonlinear integration dynamical
      system associated with Kintsch's construction-integration (CI) model is analysed
      with linear algebra tools. This addresses some theoretical questions raised and
      left unanswered by Rodenhausen (1992, Psychological Review 99, 547-549). A
      mathematical characterization for equilibrium points, which allows an a priori
      enumeration of all possible asymptotic states for the integration dynamical
      system, given a connectivity matrix, is given. The dynamics of convergence of the
      integration dynamical system is characterized in some detail as well. This
      provides a tool for understanding CI simulations and helps in particular to let
      us know to what extent the outcome will depend on the initial conditions. The
      criteria also provide a new mathematical analysis which allows for the explicit
      calculation of asymptotic states of the integration process without requiring
      computer simulation experiments. The new mathematical analysis should facilitate
      comparisons of the model's predictions with behavioural data. Copyright 2001
      Academic Press. 

PMID- 11302718
TI  - The Normal Distribution Derived from Qualitative Conditions.
AB  - The normal distribution is characterized in a measurement theoretic framework.
      The qualitative conditions guarantee that representations can be regarded as
      random variables. Additional axioms, also qualitative in the measurement sense,
      yield the normal. One characterization draws on a limit theorem. The main result
      derives the normal distribution from conjoint measurement axioms. This approach
      consists of formulating properties of a linear model as a component structure
      with error as one component. The normal distribution of errors is shown to be a
      consequence of the measurement theoretic assumptions. The possible impact of
      these results on statistical models is discussed. Copyright 2001 Academic Press. 

PMID- 11302719
TI  - A Simple Game-Theoretic Explanation for the Relationship between Group Size and
      Helping.
AB  - Consistent with evidence from some psychological studies, this paper shows that
      as there are more people who can help someone in need, the lower is the
      probability that help is forthcoming. Copyright 2001 Academic Press. 

PMID- 11302720
TI  - A Note on the Correspondence among Entail Relations, Rough Set Dependencies, and
      Logical Consequence.
AB  - In this note, we report that entail relations defined in the context of knowledge
      spaces are equivalent to the dependence relations of rough set data analysis and
      Tarski's consequence relation of monotone logic. We also discuss the connection
      between these and related structures. Copyright 2001 Academic Press. 

PMID- 11302721
TI  - CONFERENCE PROGRAM: Thirty-First European Mathematical Psychology Group Meeting.

PMID- 11302722
TI  - TELEGRAPHIC REVIEWS.

PMID- 11302723
TI  - Nitric oxide as a bioregulator of apoptosis.
AB  - Nitric oxide (NO), synthesized from l-arginine by NO synthases, is a small,
      diffusible, highly reactive molecule with dichotomous regulatory roles under
      physiological and pathological conditions. NO can promote apoptosis
      (proapoptosis) in some cells, whereas it inhibits apoptosis (antiapoptosis) in
      other cells. This complexity is a consequence of the rate of NO production and
      the interaction with biological molecules such as iron, thiols, proteins, and
      reactive oxygen species. Long-lasting production of NO acts as a proapoptotic
      modulator by activating caspase family proteases through the release of
      mitochondrial cytochrome c into the cytosol, upregulation of p53 expression,
      activation of JNK/SAPK, and altering the expression of apoptosis-associated
      proteins including Bcl-2 family proteins. However, low or physiological
      concentrations of NO prevent cells from apoptosis induced by trophic factor
      withdrawal, Fas, TNFalpha, and lipopolysaccharide. The antiapoptotic mechanism
      can be understood via expression of protective genes such as heat shock proteins,
      Bcl-2 as well as direct inhibition of the apoptotic caspase family proteases by S
      nitrosylation of the cysteine thiol. Our current understanding of the mechanisms
      by which NO exerts both pro- and antiapoptotic actions is discussed in this
      review article.

PMID- 11302724
TI  - Inactivation of NF-kappaB involved in osteoblast development through interleukin
      6.
AB  - Osteoblasts undergo a process of proliferation and differentiation and are
      responsible for bone formation. In this study, we examined the relation between
      NF-kappaB, a key transcription factor in bone metabolism, and osteoblast
      maturation. NF-kappaB activity and expression of p50, a subunit of NF-kappaB,
      decreased during development of osteoblastic MC3T3-E1 cells. The secretion of IL
      6 by osteoblast, which in combination with soluble IL-6 receptor induces
      conversion of fibroblasts to alkaline phosphatase-positive cells, also increased.
      p50 antisense oligonucleotide increased IL-6 mRNA expression. These results
      suggest that p50 regulates transcription of IL-6 and indirectly controls
      osteoblast maturation.

PMID- 11302725
TI  - Effect of angiotensin II type 2 receptor on tyrosine kinase Pyk2 and c-Jun NH2
      terminal kinase via SHP-1 tyrosine phosphatase activity: evidence from vascular
      targeted transgenic mice of AT2 receptor.
AB  - Angiotensin II (Ang II) has two major receptor isoforms, AT1 and AT2. AT1
      transphosphorylates Ca(2+)-sensitive tyrosine kinase Pyk2 to activate c-Jun NH2
      terminal kinase (JNK). Although AT2 inactivates extracellular signal-regulated
      kinase (ERK) via tyrosine phosphatases (PTP), the action of AT2 on Pyk2 and JNK
      remains undefined. Using AT2-overexpressing vascular smooth muscle cells (AT2
      VSMC) from AT2-transgenic mice, we studied these undefined actions of AT2. AT1
      mediated JNK activity was increased 2.2-fold by AT2 inhibition, which was
      abolished by orthovanadate. AT2 did not affect AT1-mediated Pyk2 phosphorylation,
      but attenuated c-Jun mRNA accumulation by 32%. The activity of src-homology 2
      domain-containing PTP (SHP-1) was significantly upregulated 1 min after AT2
      stimulation. Stable overexpression of SHP-1 dominant negative mutant in AT2-VSMC
      completely abolished AT2-mediated inhibition of JNK activation and c-Jun
      expression. These findings suggest that AT2 inhibits JNK activity by affecting
      the downstream signal of Pyk2 in a SHP-1-dependent manner, leading to a decrease
      in c-Jun expression.

PMID- 11302726
TI  - Important role of tetrahydrobiopterin in no complex formation and interdomain
      electron transfer in neuronal nitric-oxide synthase.
AB  - Neuronal nitric-oxide synthase (nNOS) is composed of a heme oxygenase domain and
      a flavin-bound reductase domain. Ca(2+)/calmodulin (CaM) is essential for
      interdomain electron transfer during catalysis, whereas the role of the
      catalytically important cofactor, tetrahydrobiopterin (H4B) remains elusive. The
      product NO appears to bind to the heme and works as a feedback inhibitor. The
      present study shows that the Fe(3+)-NO complex is reduced to the Fe(2+)-NO
      complex by NADPH in the presence of both l-Arg and H4B even in the absence of
      Ca(2+)/CaM. The complex could not be fully reduced in the absence of H4B under
      any circumstances. However, dihydrobiopterin and N(G)-hydroxy-l-Arg could be
      substituted for H4B and l-Arg, respectively. No direct correlation could be found
      between redox potentials of the nNOS heme and the observed reduction of the
      Fe(3+)-NO complex. Thus, our data indicate the importance of the pterin binding
      to the active site structure during the reduction of the NO-heme complex by NADPH
      during catalytic turnover.

PMID- 11302727
TI  - Delivery of genes encoding cardiac K(ATP) channel subunits in conjunction with
      pinacidil prevents membrane depolarization in cells exposed to chemical hypoxia
      reoxygenation.
AB  - Metabolic injury is a complex process affecting various: tissues with membrane
      depolarisation recognised as a common trigger event leading to cell death. To
      examine whether, under metabolic challenge, membrane potential homeostasis can be
      maintained by an activator of channel proteins, we here delivered Kir6.2 and
      SUR2A genes, which encode cardiac K(ATP) channel subunits, into a somatic cell
      line lacking native K(ATP) channels (COS-7 cells). Chemical hypoxia-reoxygenation
      was simulated in COS-7 cells by addition and removal of the mitochondrial poison
      2,4 dinitrophenol (DNP). The membrane potential of COS-7 cells at rest was -31 +/
      3 mV. This value did not change following 3 min-long exposure to DNP (-32 +/- 4
      mV). In contrast, washout of DNP induced significant membrane depolarisation (-17
      +/- 2 mV). Delivery of Kir6.2/SUR2A genes did not change cellular response to
      hypoxia-reoxygenation. Similarly, pinacidil, potassium channel opener, did not
      have effect on hypoxia-reoxygenation-induced membrane depolarisation in cells
      lacking recombinant K(ATP) channel subunits. However, gene delivery combined with
      pinacidil prevented membrane depolarisation induced by hypoxia-reoxygenation.
      This effect of pinacidil, in cells expressing Kir6.2/SUR2A, was observed
      regardless of whether pinacidil was added only during hypoxia or reoxygenation.
      The present study demonstrates that combined use of K(ATP) channel subunits gene
      delivery and pharmacological targeting of recombinant proteins can be used to
      efficiently control membrane potential under hypoxia-reoxygenation.

PMID- 11302728
TI  - Human BTR1, a new bicarbonate transporter superfamily member and human AE4 from
      kidney.
AB  - We report the cloning, characterization, and chromosomal localization of two
      novel human members of the bicarbonate transporter superfamily, BTR1 (Bicarbonate
      Transporter Related protein-1) and AE4 (Anion Exchange protein 4). BTR1 is a
      novel mammalian protein. The BTR1 gene maps to chromosome 20p12 and encodes a 100
      kDa protein predominantly expressed in the kidney, salivary glands, testis,
      thyroid glands, and trachea. The AE4 gene maps to chromosome 5q23-31 and encodes
      a 104 kDa protein expressed mainly in the kidney. Human AE4 shares 84% identity
      with the recently reported rabbit AE4, a sodium independent, Cl(-)/HCO(-)(3)
      exchanger located on the apical membrane of beta-intercalated kidney cells.

PMID- 11302729
TI  - Expression of survivin in HTLV-I-infected T-cell lines and primary ATL cells.
AB  - Human T-cell leukemia virus type I (HTLV-I) is the etiological agent of adult T
      cell leukemia (ATL), although the precise mechanisms involved in the
      transformation process have not yet been defined. Deregulated inhibition of
      apoptosis may facilitate the insurgence of leukemia. Survivin is an inhibitor of
      apoptosis and considered to play a role in oncogenesis. We investigated the
      expression of survivin in HTLV-I-infected T-cell lines and primary ATL cells.
      Northern blot analysis showed expression of survivin transcript in all 9 HTLV-I
      positive T-cell lines. High survivin expression levels were detected in primary
      cells of patients with acute-type ATL, but no such expression was noted in the
      cells of chronic-type ATL or normal peripheral blood mononuclear cells. Treatment
      of an HTLV-I-infected T-cell line, MT-1, with survivin specific antisense
      oligonucleotide resulted in reduced cell growth. Our results suggest that
      expression of survivin may play an important role in the development and
      pathogenesis of ATL.

PMID- 11302730
TI  - Chimeric caspase molecules with potent cell killing activity in apoptosis
      resistant cells.
AB  - Cellular defects which prevent apoptotic cell death can result in the generation
      of hyperproliferative disorders and can prevent the effective treatment of such
      diseases. The majority of cellular defects which result in apoptosis resistance
      lie upstream of caspase activation. We have described chimeric caspase molecules
      consisting of the prodomain of caspase-2 fused to the amino terminus of caspase
      3, and which are tagged at the carboxyl terminus with green fluorescent protein
      (GFP) to allow direct visualisation of transfected cells. Here we show that these
      chimeric caspase molecules possess potent, rapid cell-killing activity in cell
      lines which display a range of defects resulting in apoptosis resistance.

PMID- 11302731
TI  - Cadmium induces phosphorylation of p53 at serine 15 in MCF-7 cells.
AB  - When MCF-7 cells were incubated with 10 or 20 microM CdCl(2), p53 protein level
      increased after 18 h. Among serines in p53 protein immunoprecipitated from cells
      treated with CdCl(2), only Ser 15 was phosphorylated. No clear phosphorylation
      was found on Ser 6, 9, 20, 37, and 392. Accumulation of p53 protein
      phosphorylated at Ser 15 was also found after 18 h exposure. While
      phosphorylation of extracellular signal-regulated protein kinase, c-Jun NH2
      terminal kinase and p38 was found in cells treated with CdCl(2), treatment with
      U0126, LL-Z1640-2, or SB203580 did not suppress Ser 15 phosphorylation. On the
      other hand, treatment with wortmannin or caffeine suppressed CdCl(2)-induced Ser
      15 phosphorylation and accumulation of p53 protein. The present results showed
      that cadmium induces phosphorylation of p53 at Ser 15 in MCF-7 cells depending on
      phosphatidylinositol 3-kinase related kinases, but not on mitogen-activated
      protein kinases.

PMID- 11302732
TI  - Stimulation of IGF-binding protein-1 secretion by AMP-activated protein kinase.
AB  - Insulin-like growth factor-binding protein-1 (IGFBP-1) is stimulated during
      intensive exercise and in catabolic conditions to very high concentrations, which
      are not completely explained by known regulators such as insulin and
      glucocorticoids. The role of AMP-activated protein kinase (AMPK), an important
      signaling system in lipid and carbohydrate metabolism, in regulating IGFBP-1 was
      studied in H4-II-E rat hepatoma cells. Arsenic(III) oxide and 5-aminoimidazole-4
      carboxamide-riboside (AICAR) were used as activators. AICAR (150 microM)
      stimulated IGFBP-1 secretion twofold during a 5-h incubation (P = 0.002). Insulin
      (100 ng/ml) inhibited IGFBP-1 by 80% (P < 0.001), but this was completely
      abolished in the presence of 150 microM AICAR. The effect of dexamethasone in
      stimulating IGFBP-1 threefold was additive to the effect of AICAR (P < 0.001)
      and, in the presence of AICAR, was incompletely inhibited by insulin. In
      conclusion AMPK is identified as a novel regulatory pathway for IGFBP-1,
      stimulating secretion and blocking the inhibitory effect of insulin.

PMID- 11302733
TI  - xCt cystine transporter expression in HEK293 cells: pharmacology and
      localization.
AB  - xCT, the core subunit of the system x(c)(-) high affinity cystine transporter,
      belongs to a superfamily of glycoprotein-associated amino acid transporters.
      Although xCT was shown to promote cystine transport in Xenopus oocytes, little
      work has been done with mammalian cells (Sato, H., Tamba, M., Ishii, T., and
      Bannai, S. J. Biol. Chem. 274, 11455-11458, 1999). Therefore, we have constructed
      mammalian expression vectors for murine xCT and its accessory subunit 4F2hc and
      transfected them into HEK293 cells. We report that this transporter binds cystine
      with high affinity (81 microM) and displays a pharmacological profile expected
      for system x(c)(-). Surprisingly, xCT transport activity in HEK293 cells is not
      dependent on the co-expression of the exogenous 4F2hc. Expression of GFP-tagged
      xCT indicated a highly clustered plasma membrane and intracellular distribution
      suggesting the presence of subcellular domains associated with combating
      oxidative stress. Our results indicate that HEK293 cells transfected with the xCT
      subunit would be a useful vehicle for future structure-function and pharmacology
      experiments involving system x(c)(-).

PMID- 11302734
TI  - Effects of cAMP on intercellular coupling and osteoblast differentiation.
AB  - Bone-forming cells are organized in a multicellular network interconnected by gap
      junctions. Direct intercellular communication via gap junctions is an important
      component of bone homeostasis, coordinating cellular responses to external
      signals and promoting osteoblast differentiation. The cAMP pathway, a major
      intercellular signal transduction mechanism, regulates osteoblastic function and
      metabolism. We investigated the effects of this second messenger on junctional
      communication and on the expression of differentiation markers in human HOBIT
      osteoblastic cells. Increased levels of cAMP induce posttranslational
      modifications (i.e., phosphorylations) of connexin43 and enhancement of gap
      junction assembly, resulting in an increased junctional permeance to Lucifer
      yellow and to a positive modulation of intercellular Ca(2+) waves. Increased
      intercellular communication, however, was accompanied by a parallel decrease of
      alkaline phosphatase activity and by an increase of osteocalcin expression. cAMP
      dependent stimulation of cell-to-cell coupling induces a complex modulation of
      bone differentiation markers.

PMID- 11302735
TI  - Isolation and characterization of cultured human periodental ligament fibroblast
      specific cDNAs.
AB  - The molecular mechanisms that control the function of periodontal ligament (PDL)
      fibroblasts remain unclear. We speculated that the character of differentiating
      PDL fibroblasts is defined by the altered expansion of specific genes not found
      in neighboring gingival fibroblasts in the periodontium. To expand this set,
      subtractive hybridization was applied between cultured human PDL and gingival
      fibroblasts to identify genes differentially expressed in PDL. Consequently five
      candidate clones, PDLs (periodontal ligament specific) 5, -17, -22, -25, and -31
      were identified and characterized by homology search, Northern analysis, and in
      situ hybridization. Although the mRNAs of these clones were expressed by bone
      marrow cells and rarely by gingival fibroblasts, the highest expression was
      detected in the PDL cells, which were uniformly distributed throughout the whole
      PDL. Amongst the five candidate clones, we focused on PDLs17, because it is a
      hypothetical protein whose biological function has not been reported yet in the
      database. Polyclonal antiserum raised against PDLs17 peptide was made, and
      stained the PDL fibroblasts, osteoblast-like cells and stromal cells in the bone
      marrow, but not gingival fibroblasts. The results suggest that clones, PDLs5, 
      17, -22, -25, and -31 may be used as PDL fibroblast-specific markers, and that
      PDLs17 could act as an important factor in the differentiation process of PDL
      fibroblasts.

PMID- 11302736
TI  - Shc mediates ligand-induced internalization of epidermal growth factor receptors.
AB  - In order to clarify the physiological relevance of the interaction between Shc
      and adaptins, components of plasma membrane-coated pit adaptor complex AP2, we
      investigated the role of Shc in ligand-induced endocytosis of epidermal growth
      factor (EGF) receptors. In vitro peptide binding assay showed that alpha-adaptin
      bound to the wild-type peptide corresponding to amino acids 346-355 of Shc,
      RDLFDMKPFE, but not to the mutant peptide in which both phenylalanines at 349 and
      354 were substituted for alanines (FA). Using adenovirus vectors carrying a
      herpes simplex virus epitope-tagged 52-kDa wild-type Shc and Shc FA, we examined
      the interaction between Shc, AP2, and EGF receptors in intact cells. Alpha
      adaptin bound to wild-type Shc in an EGF-dependent manner, whereas EGF-dependent
      association of alpha-adaptin with Shc FA was markedly reduced. In addition, EGF
      increased the amount of alpha-adaptin coprecipitated with EGF receptors in cells
      expressing wild-type Shc but not Shc FA. These results suggest that EGF
      stimulates Shc-AP2 complex formation and association of Shc-AP2 complexes with
      EGF receptors. Internalization assay showed that (125)I-EGF internalization was
      reduced in cells overexpressing Shc FA. Immunofluorescence study showed that
      punctate staining along the plasma membrane border as well as punctate pattern
      characteristic of cytoplasmic vesicles near the plasma membrane was enhanced in
      cells expressing wild-type Shc. These results suggest, therefore, the implication
      of Shc in ligand-induced endocytosis of EGF receptors in intact cells.

PMID- 11302737
TI  - Flavonoid B-ring chemistry and antioxidant activity: fast reaction kinetics.
AB  - Rapid scavenging of the model stable radical cation, ABTS(*+), has been applied
      to screen for the antioxidant activity of flavonoids. The reaction follows two
      distinct phases. For compounds with a monophenolic B-ring there is a rapid
      initial phase of reduction of ABTS(*+) within 0.1 s with no further change in the
      subsequent 2.9 s. In contrast, compounds with a catechol-containing B ring follow
      a fast initial scavenging phase with a slow secondary phase. Flavonoids with an
      unsubstituted B ring do not react within this time scale. The findings suggest
      that the structure of the B ring is the primary determinant of the antioxidant
      activity of flavonoids when studied through fast reaction kinetics.

PMID- 11302738
TI  - Induction of antigen-specific Th1-biased immune responses by plasmid DNA in
      schistosoma-infected mice with a preexistent dominant Th2 immune profile.
AB  - A requisite for vaccines to confer protection against intracellular infections
      such as Human Immunodeficiency Virus or Mycobacterium tuberculosis is their
      capacity to induce Th1 immune responses. However, they may fail to do so in
      Africa and South East Asia, where most individuals have a dominant preexistent
      Th2 immune profile, due to persistent helminthic parasitic infections, which may
      undermine any Th1 response. It is well established that DNA vaccines induce
      strong Th1 biased immune responses against an encoded antigen, depending on the
      route and mode of immunization. Here, we demonstrate that intradermal
      immunization with plasmid DNA encoding beta-gal (pCMV-LacZ) of Schistosoma
      infected mice, with preexistent dominant Th2 immune background, induce a strong
      Th1 anti-beta-gal response, as opposed to immunized with beta-gal only.
      Importantly, the established protective Th2 immune response to schistosomes was
      not disrupted. These findings strongly support the possibility of using plasmid
      DNA as a Th1 inducing adjuvant when immunizing populations with a strong
      preexistent Th2 immune profile.

PMID- 11302739
TI  - Polyamine and thiol metabolism in Trypanosoma granulosum: similarities with
      Trypanosoma cruzi.
AB  - Concentrations of free polyamines were investigated in Trypanosoma granulosum
      cultured in a semidefined medium containing traces of polyamines. Spermidine
      content peaked in early logarithmic growth while putrescine was not detectable.
      Unlike African trypanosomes and Leishmania, spermine was measured at equivalent
      amounts to spermidine in mid to late logarithmic stage cells. Addition of d,l
      alpha-difluoromethylornithine to cultures did not decrease polyamine content nor
      was ornithine decarboxylase activity detected. In contrast, incubation of
      parasites with tritiated putrescine showed rapid uptake and subsequent conversion
      to spermidine and spermine. At late logarithmic growth, parasites contained
      glutathione (77% of total sulphydryl groups) and ovothiol A as major low
      molecular mass thiols with glutathionylpolyamine conjugates undetectable.
      However, the addition of exogenous putrescine elevated trypanothione and
      glutathionylspermidine content to 48% of total sulphydryl groups.
      Correspondingly, the addition of exogenous cadaverine increased homotrypanothione
      content. This first report of polyamines and low molecular mass thiols in
      Trypanosoma granulosum indicates intriguing similarities with the metabolism of
      the human pathogen Trypanosoma cruzi.

PMID- 11302740
TI  - Cloning and expression of human rotavirus spike protein, VP8*, in Escherichia
      coli.
AB  - A system for the expression and purification of soluble VP8*, part of the human
      rotavirus (HRV) spike protein, was established by expressing VP8* as a fusion
      protein with glutathione S-transferase (GST). VP8 cDNA, from the Wa strain of
      HRV, was prepared by RT-PCR, cloned into a pUC18 plasmid, and inserted into a
      pGEX-4T-2 GST fusion vector. The GST-VP8* fusion protein was expressed in
      Escherichia coli, and the VP8* was purified by Glutathione Sepharose 4B affinity
      chromatography, yielding 1.8 mg VP8*/L culture. The purified VP8* was used to
      vaccinate chickens, eliciting antibodies which displayed high neutralization
      activity against the Wa strain of HRV, suggesting its use for the induction of
      specific neutralizing antibodies for potential immunotherapeutic applications for
      the prevention of HRV infection.

PMID- 11302741
TI  - Binding of a denatured heme protein and ATP to erythroid spectrin.
AB  - Spectrin is a large, worm-like cytoskeletal protein that is abundant in all cell
      types. The denatured heme enzyme, horseradish peroxidase showed significant
      decrease in the reactivation yield, after 30 min of refolding, in presence of
      increasing concentrations of spectrin from that in the absence. This indicated
      that spectrin could bind denatured HRP and inhibit their refolding. In presence
      of 1 mM ATP and 10 mM MgCl(2) the spectrin binding of denatured HRP is abolished.
      This activity of decreasing the reactivation yield was found to be ATP-dependent
      and the denatured enzyme after 30 min refolding in the presence of spectrin,
      pretreated with Mg/ATP, showed about 40% increase in the reactivation yield
      compared to the same in absence of spectrin. Fluorescence spectroscopic studies
      indicated binding of ATP to native spectrin showing concentration-dependent
      quenching of tryptophan fluorescence by ATP. The apparent dissociation constant
      of binding of ATP to spectrin was estimated to be 1.1 mM. A high affinity binding
      of spectrin with denatured HRP has been characterized (K(d) = 16 nM). Since these
      properties are similar to those of established molecular chaperone proteins,
      these data indicate that spectrin might have a chaperone-like function in
      erythrocytes.

PMID- 11302742
TI  - Mutation of human molybdenum cofactor sulfurase gene is responsible for classical
      xanthinuria type II.
AB  - Drosophila ma-l gene was suggested to encode an enzyme for sulfuration of the
      desulfo molybdenum cofactor for xanthine dehydrogenase (XDH) and aldehyde oxidase
      (AO). The human molybdenum cofactor sulfurase (HMCS) gene, the human ma-l
      homologue, is therefore a candidate gene responsible for classical xanthinuria
      type II, which involves both XDH and AO deficiencies. However, HMCS has not been
      identified as yet. In this study, we cloned the HMCS gene from a cDNA library
      prepared from liver. In two independent patients with classical xanthinuria type
      II, we identified a C to T base substitution at nucleotide 1255 in the HMCS gene
      that should cause a CGA (Arg) to TGA (Ter) nonsense substitution at codon 419. A
      classical xanthinuria type I patient and healthy volunteers lacked this mutation.
      These results indicate that a functional defect of the HMCS gene is responsible
      for classical xanthinuria type II, and that HMCS protein functions to provide a
      sulfur atom for the molybdenum cofactor of XDH and AO.

PMID- 11302744
TI  - Menin, a gene product responsible for multiple endocrine neoplasia type 1,
      interacts with the putative tumor metastasis suppressor nm23.
AB  - Although the gene responsible for multiple endocrine neoplasia type 1 (MEN1) has
      been identified, the function of its gene product, menin, is unknown. To examine
      the biological role of the MEN1 gene, we searched for associated proteins with a
      yeast two-hybrid system using the MEN1 cDNA fragment as bait. On screening a rat
      fetal brain embryonic day 17 library, in which a high level of MEN1 expression
      was detected, we identified a putative tumor metastasis suppressor
      nm23/nucleoside diphosphate (NDP) kinase as an associated protein. This finding
      was confirmed by in vitro interaction assays based on glutathione S-transferase
      pull down experiments. The association required almost the entire menin protein,
      and several missense MEN1 mutations reported in MEN1 patients caused a loss of
      the binding activity for nm23. This result suggests that this interaction may
      play important roles in the biological functions of the menin protein, including
      tumor suppressor activity.

PMID- 11302743
TI  - Myristoylation of human immunodeficiency virus type 1 gag protein is required for
      efficient env protein transportation to the surface of cells.
AB  - Highly conserved amino acids in the N-terminal region of the human
      immunodeficiency virus type 1 (HIV-1) Pr55(gag) are recognized to be critical for
      the attachment of myristic acid. We previously reported that the env protein was
      not detected on the cell surface by blocking of N-myristoylation of Pr55(gag)
      with N-myristoyl glycinal diethylacetal. Here, we constructed a mutant by
      substituting the N-terminal glycine of Pr55(gag) with alanine to demonstrate that
      N-myristoylation of Pr55(gag) is required for efficient env protein
      transportation to the cell surface. The expression level of the env protein on
      the surface of Jurkat cells transfected with the myristoylation-defective
      phenotype was observed to be significantly reduced by electron microscopic
      analyses with a gold-labeled monoclonal antibody against the env protein. In
      addition, Jurkat cells transfected with the myristoylation-defective phenotype
      lost the ability of envelope-mediated cell-to-cell fusion. The results suggest
      that N-myristoylation of the HIV-1 gag protein is necessary for efficient env
      protein transportation to the cell surface.

PMID- 11302745
TI  - The role of heat shock protein 70 in vitamin D receptor function.
AB  - We previously demonstrated that the 1alpha,25-dihydroxyvitamin D(3) receptor
      (VDR) interacts with the constitutive heat shock protein, hsc70 in vitro, and
      with DnaK (Biochem. Biophys. Res. Commun. 260, 446-452, 1999). The biological
      significance of VDR-heat shock protein interactions, however, is unknown. To
      examine the role of such interactions in eukaryotic cells, we heterologously
      expressed VDR and RXRalpha together with a vitamin D-responsive reporter system
      in Saccharomyces cerevisiae and examined the consequences of heat shock protein
      70 gene (SSA) deletion in these cells. We show that heterologously expressed VDR
      associates with the yeast cytosolic hsp70 protein, Ssa1p. Deletion of the SSA2,
      SSA3, and SSA4 genes and reduction of Ssa1p activity, reduces the intracellular
      concentrations of the VDR and its heterodimeric partner, RXRalpha and reduces the
      activity of a vitamin D-dependent gene. Hsp70-like chaperone proteins play a role
      in controlling concentrations of the VDR within the cell.

PMID- 11302746
TI  - FTIR study of horseradish peroxidase in reverse micelles.
AB  - Fourier transform infrared (FTIR) method was used to study the secondary
      structures of horseradish peroxidase (HRP) in aqueous solution and in reverse
      micelles for the first time. Results indicated that the structure of HRP in
      sodium bis(2-ethylhexy)sulfosuccinate (AOT) reverse micelles was close to that in
      aqueous solution. In cetyltrimethylammonium bromide (CTAB) and sodium dodecylfate
      (SDS) reverse micelles the position of some bands changed. Results indicated that
      the secondary structure had a close relationship with the surfactant species of
      the reverse micelles. Among the three types of reverse micelles, the system of
      AOT reverse micelles was probably the most beneficial reaction media to HRP.

PMID- 11302747
TI  - Purification and characterization of three antifungal proteins from cheeseweed
      (Malva parviflora).
AB  - Three potent antimicrobial proteins were purified from cheeseweed (Malva
      parviflora) seeds. These antimicrobial proteins, named CW-3, CW-4, and CW-5,
      showed different antimicrobial spectrum and potency compared to the two
      heterologous antimicrobial proteins (CW-1 and CW-2) purified previously. CW-3 and
      CW-4 possess antimicrobial activities against Phytophthora infestans (Pi), but
      not Fusarium graminearum (Fg). A database search indicated that CW-3 shares high
      homology to cotton vicilin, an abundant seed storage protein. CW-4 shares
      homology to 2S albumin, another seed storage protein from cotton. CW-5 has
      antimicrobial activity against Fg, but no activity against Pi was observed at
      protein concentration up to 50 ppm. Under low salt condition, CW-5 showed potent
      antimicrobial activity against Fg, but under high salt condition, the
      antimicrobial activity was drastically diminished. Database search indicated that
      CW-5 has high homology to a lipid transfer protein from grape. The IC(50) values
      of the three purified antimicrobial proteins under both low and high salt
      conditions were determined. The isolation of five antimicrobial proteins for the
      first time from a single plant source provides further understanding of the plant
      innate defense system and insight on how plants evolve their complex and
      complementary antimicrobial system that is important in the early stage of
      development.

PMID- 11302748
TI  - Serine residues 110 and 114 are required for agonist binding but not antagonist
      binding to the melatonin MT(1) receptor.
AB  - Site-directed mutation of serine 110 (Ser(3.35)) and serine 114 (Ser(3.39)) in
      the human melatonin MT(1) receptor to alanine residues reduced ligand binding
      affinities of seven known melatonin receptor agonists and partial agonists by 3-
      to 15-fold. These mutants also displayed a relative reduction in their affinities
      for melatonin-mediated functional responses of 30- and 14-fold, respectively. In
      contrast to the observed effects of the agonists and partial agonists, the
      melatonin receptor antagonist luzindole was found to bind to mutants Ser(3.35)Ala
      and Ser(3.39)Ala with affinities equivalent to that determined for the wild-type
      melatonin MT(1) receptor. Luzindole was subsequently confirmed as an antagonist
      of melatonin-mediated functional responses for both mutant receptors. These
      studies have identified that in the human melatonin MT(1) receptor, Ser(3.35) and
      Ser(3.39), in transmembrane domain 3, are critical for the formation of the high
      affinity ligand binding site for agonists and partial agonists but not for the
      antagonist luzindole.

PMID- 11302749
TI  - Roles of histidine residues in tobacco acetolactate synthase.
AB  - Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis
      of valine, leucine, and isoleucine in plants and microorganisms. ALS is the
      target of several structurally diverse classes of herbicides, including
      sulfonylureas, imidazolinones, and triazolopyrimidines. The roles of three well
      conserved histidine residues (H351, H392, and H487) in tobacco ALS were
      determined using site-directed mutagenesis. Both H487F and H487L mutations
      abolished the enzymatic activity as well as the binding affinity for the cofactor
      FAD. Nevertheless, the mutation of H487F did not affect the secondary structure
      of the ALS. The K(m) values of H351M, H351Q, and H351F are approximately 18-, 60
      , and fivefold higher than that of the wild-type ALS, respectively. Moreover, the
      K(c) value of H351Q for FAD is about 137-fold higher than that of wALS. Mutants
      H351M and H351Q showed very strong resistance to Londax (a sulfonylurea) and
      Cadre (an imidazolinone), whereas mutant H351F was weakly resistant to them.
      However, the secondary structures of mutants H351M and H351Q appeared to be
      different from that of wALS. The mutation of H392M did not have any significant
      effect on the kinetic parameters nor the resistance to ALS-inhibiting herbicides.
      These results suggest that the His487 residue is located at the active site of
      the enzyme and is likely involved in the binding of cofactor FAD in tobacco ALS.
      Mutational analyses of the His351 residue imply that the active site of the ALS
      is probably close to its binding site of the herbicides, Londax and Cadre.

PMID- 11302750
TI  - Rpg1p/Tif32p, a subunit of translation initiation factor 3, interacts with actin
      associated protein Sla2p.
AB  - The yeast two-hybrid system was used to screen for proteins that interact in vivo
      with Saccharomyces cerevisiae Rpg1p/Tif32p, the large subunit of the translation
      initiation factor 3 core complex (eIF3). Eight positive clones encoding portions
      of the SLA2/END4/MOP2 gene were isolated. They overlapped in the region of amino
      acids 318-550. Subsequent deletion analysis of Sla2p showed that amino acids 318
      373 were essential for the two-hybrid protein-protein interaction. The N-terminal
      part of Rpg1p (aa 1-615) was essential and sufficient for the Rpg1p-Sla2p
      interaction. A coimmunoprecipitation assay provided additional evidence for the
      physical interaction of Rpg1p/Tif32p with Sla2p in vivo. Using immunofluorescence
      microscopy, Rpg1p and Sla2p proteins were colocalized at the patch associated
      with the tip of emerging bud. Considering the essential role of Rpg1p as the
      large subunit of the eIF3 core complex and the association of Sla2p with the
      actin cytoskeleton, a putative role of the Rpg1p-Sla2p interaction in localized
      translation is discussed.

PMID- 11302751
TI  - Transport function of the naturally occurring pathogenic polycystin-2 mutant,
      R742X.
AB  - Most patients with autosomal dominant polycystic kidney disease (ADPKD) harbor
      mutations truncating polycystin-1 (PC1) or polycystin-2 (PC2), products of the
      PKD1 and PKD2 genes, respectively. A third member of the polycystin family,
      polycystin-L (PCL), was recently shown to function as a Ca(2+)-modulated
      nonselective cation channel. More recently, PC2 was also shown to be a
      nonselective cation channel with comparable properties to PCL, though the
      membrane targeting of PC2 likely varies with cell types. Here we show that PC2
      expressed heterologously in Xenopus oocytes is targeted to intracellular
      compartments. By contrast, a truncated form of mouse PC2 corresponding to a
      naturally occurring human mutation R742X is targeted predominantly to the plasma
      membrane where it mediates K(+), Na(+), and Ca(2+) currents. Unlike PCL, the
      truncated form does not display Ca(2+)-activated transport activities, possibly
      due to loss of an EF-hand at the C-terminus. We propose that PC2 forms ion
      channels utilizing structural components which are preserved in the R742X form of
      the protein. Implications for epithelial cell signaling are discussed.

PMID- 11302752
TI  - Functional interaction of transcriptional coactivator ASC-2 and C/EBPalpha in
      granulocyte differentiation of HL-60 promyelocytic cell.
AB  - HL-60 promyelocytic cells were treated with retinoic acid (RA) to stimulate
      granulocyte differentiation. CCAAT/enhancer binding protein alpha (C/EBPalpha) is
      known to be the molecular switch during early hematopoietic developmental events
      that direct cells to the granulocytic pathway. Here we show that the coactivator
      activating signal cointegrator-2 (ASC-2) plays an important role in
      differentiation of HL-60 cells into granulocytes by mediating C/EBPalpha-induced
      gene transcription. The differentiation inducer RA increased mRNA and protein
      expression of ASC-2. The protein-protein interaction of C/EBPalpha and ASC-2 was
      detected by coimmunoprecipitation during granulocyte differentiation.
      Subsequently, GST-pull-down assay revealed that the N-terminal transactivation
      domain of C/EBPalpha could interact with ASC-2. This functional interaction of
      ASC-2 with C/EBPalpha drove a synergistic enhancement of C/EBPalpha-dependent
      transactivation and overexpression of the N-terminal C/EBPalpha protein in HL-60
      cells inhibited ASC-2 responsiveness for C/EBPalpha activity in granulocyte
      differentiation, indicating C/EBPalpha dependency of ASC-2 activity. Taken
      together, these results suggest that the differentiation-dependent expressed ASC
      2 protein physically and functionally interacts with C/EBPalpha and increases its
      transactivation activity, regulating specific gene transcription for granulocyte
      differentiation.

PMID- 11302753
TI  - Nearly instantaneous, cation-independent, high selectivity nucleic acid
      hybridization to DNA microarrays.
AB  - Hybridization rate enhancement has been demonstrated for high molecular weight
      DNA target binding to a microarray. Microarrays were fabricated using biotin
      modified oligonucleotides complexed with streptavidin (SA), which serves as an
      attachment to the underlying surface. It is shown that at low salt and pH 5,
      where SA develops a positive charge, duplex formation becomes at least 80-fold
      faster than seen under standard conditions, where SA is neutral or anionic.
      Duplex formation becomes independent of solution state cation concentration in
      the low pH state, under conditions where specificity remains high. The utility of
      such applied surface science is discussed.

PMID- 11302754
TI  - Two distinct 4-hydroxynonenal metabolizing glutathione S-transferase isozymes are
      differentially expressed in human tissues.
AB  - The two previously reported human glutathione S-transferase isozymes, hGST5.8 and
      hGSTA4-4, have been suggested to be similar because of their comparable
      activities toward 4-hydroxynonenal-GSH conjugation. Here, we demonstrate that
      hGST5.8 and hGSTA4-4 are distinct. Antibodies raised against hGSTA4-4 did not
      recognize hGST5.8, and antibodies raised against mouse GSTA4-4 that cross-react
      with hGST5.8 did not recognize hGSTA4-4. The pI value of hGSTA4-4 was found to be
      8.4, as opposed to the pI value of 5.8 for hGST5.8. The two isozymes are
      differentially expressed in human tissues and there are significant differences
      in their kinetic properties. While both isozymes showed a strong expression in
      liver and testis, hGSTA4-4 was not detected in brain where hGST5.8 was present.
      In the pancreas, a strong expression of hGST5.8 was observed while hGSTA4-4 was
      barely detectable in this tissue.

PMID- 11302755
TI  - The approximately ideal, more or less free distribution.
AB  - We present the minimum set of requirements necessary and sufficient to represent
      the foraging behaviour of an animal, and its utilisation of food, in order to
      explore the emergent properties of behaviour that allow animals to reduce their
      hunger. We present an individual-based model of foraging that provides a simple
      quantification of the requirements, which is sufficiently simple to yield some
      analytical results. Complex interactions beyond the scope of analysis have been
      explored through simulating animals foraging in regenerating patchy environments.
      In most cases the populations pass into equilibrium distributions which appear to
      be stable. The equilibria always approximate closely to the ideal free
      distribution, although typically with a small degree of undermatching.
      (Undermatching is the term applied to the departure from the ideal free
      distribution caused by a smaller proportion of the population than expected
      occupying areas with a higher than average regeneration rate). The model
      therefore implies that the distribution, hitherto accounted for in terms of ESSs
      may, in fact, be simply an effect of the animal's utilization of the food it
      collects to reduce its hunger. The model defines a specific feeling rate, v, the
      rate at which an animal can feed on a unit of food. This is a function of three
      parameters, v1, the specific feeding rate when alone, v(infinity), the rate,
      possibly zero, at which it can feed in the presence of an indefinitely large
      number of conspecifics, and n1/2, the number of conspecifics that cause v to take
      the value (v1+v(infinity)/2. Exploitation competition in the absence of
      interference is represented by setting v1 = v(infinity). Differences in
      competitive ability in exploitation have been represented by simulating animals
      with a range of values of v1, those with the larger values, feeding more rapidly,
      being the more effective competitors, and those with the lower values being the
      less effective. Interference competition is represented by setting v1 >
      v(infinity) and social facilitation by v1 < v(infinity). Individual differences
      in the strength of interaction are represented by different values of n(1/2). In
      competition, the animals with the larger values of n(1/2) are the more effective
      competitors: in facilitation, they are the less effective facilitators. The
      addition of physiological and behavioural detail makes very little alteration to
      the emergent equilibria, always close to the ideal free distribution, almost
      always showing undermatching.

PMID- 11302756
TI  - A stochastic model for evolution of sociality in insects.
AB  - We study population biology of eusocial insects such as Ropalidia marginata
      through a stochastic model based on random (matrix) difference equations. This
      facilitates a study of dynamics of such populations when the survival and other
      rates vary randomly over time. The worker-brood relatedness, which is a function
      of the underlying population structure, can be used to explain theories on the
      evolution of altruism. The effect of demographic parameters and the queen
      takeover probabilities on the worker-brood relatedness has been studied. Based on
      the proposed model, we simulate insect colonies where queens are replaced.
      Simulation results help us to study the effect of various factors on the worker
      brood relatedness. Further, we study two estimators of the worker-brood
      relatedness and suggest procedures for estimating their standard errors.
      Approximate confidence intervals for the same can be constructed with the help of
      these results.

PMID- 11302757
TI  - The dynamics of two diffusively coupled predator-prey populations.
AB  - I analyze the dynamics of predator and prey populations living in two patches.
      Within a patch the prey grow logistically and the predators have a Holling type
      II functional response. The two patches are coupled through predator migration.
      The system can be interpreted as a simple predator-prey metapopulation or as a
      spatially explicit predator-prey system. Asynchronous local dynamics are presumed
      by metapopulation theory. The main question I address is when synchronous and
      when asynchronous dynamics arise. Contrary to biological intuition, for very
      small migration rates the oscillations always synchronize. For intermediate
      migration rates the synchronous oscillations are unstable and I found periodic,
      quasi-periodic, and intermittently chaotic attractors with asynchronous dynamics.
      For large predator migration rates, attractors in the form of equilibria or limit
      cycles exist in which one of the patches contains no prey. The dynamical behavior
      of the system is described using bifurcation diagrams. The model shows that
      spatial predator-prey populations can be regulated through the interplay of local
      dynamics and migration.

PMID- 11302758
TI  - The coalescent in an island model of population subdivision with variation among
      demes.
AB  - A simple genealogical structure is found for a general finite island model of
      population subdivision. The model allows for variation in the sizes of demes, in
      contributions to the migrant pool, and in the fraction of each deme that is
      replaced by migrants every generation. The ancestry of a sample of non
      recombining DNA sequences has a simple structure when the sample size is much
      smaller than the total number of demes in the population. This allows an
      expression for the probability distribution of the number of segregating sites in
      the sample to be derived under the infinite-sites mutation model. It also yields
      easily computed estimators of the migration parameter for each deme in a multi
      deme sample. The genealogical process is such that the lineages ancestral to the
      sample tend to accumulate in demes with low migration rates and/or which
      contribute disproportionately to the migrant pool. In addition, common ancestor
      or coalescent events tend to occur in demes of small size. This provides a
      framework for understanding the determinants of the effective size of the
      population, and leads to an expression for the probability that the root of a
      genealogy occurs in a particular geographic region, or among a particular set of
      demes.

PMID- 11302759
TI  - Effects of population size and metapopulation dynamics on a mating-system
      polymorphism.
AB  - The evolutionary dynamics of neutral alleles under the Wright-Fisher model are
      well understood. Similarly, the effect of population turnover on neutral genetic
      diversity in a metapopulation has attracted recent attention in theoretical
      studies. Here we present the results of computer simulations of a simple model
      that considers the effects of finite population size and metapopulation dynamics
      on a mating-system polymorphism involving selfing and outcrossing morphs. The
      details of the model are based on empirical data from dimorphic populations of
      the annual plant Eichhornia paniculata, but the results are also of relevance to
      species with density-dependent selfing rates in general. In our model, the prior
      selfing rate is determined by two alleles segregating at a single diploid locus.
      After prior selfing occurs, some remaining ovules are selfed through competing
      self-fertilisation in finite populations as a result of random mating among
      gametes. Fitness differences between the mating-system morphs were determined by
      inbreeding depression and pollen discounting in a context-dependent manner.
      Simulation results showed evidence of frequency dependence in the action of
      pollen discounting and inbreeding depression in finite populations. In
      particular, as a result of selfing in outcrossers through random mating among
      gametes, selfers experienced a "fixation bias" through drift, even when the
      mating-system locus was selectively neutral. In a metapopulation, high colony
      turnover generally favoured the fixation of the outcrossing morph, because
      inbreeding depression reduced opportunities for colony establishment by selfers
      through seed dispersal. Our results thus demonstrate that population size and
      metapopulation processes can lead to evolutionary dynamics involving pollen and
      seed dispersal that are not predicted for large populations with stable
      demography.

PMID- 11302760
TI  - Wave of chaos: new mechanism of pattern formation in spatio-temporal population
      dynamics.
AB  - The dynamics of a simple prey-predator system is described by a system of two
      reaction- diffusion equations with biologically reasonable non-linearities
      (logistic growth of the prey, Holling type II functional response of the
      predator). We show that, when the local kinetics of the system is oscillatory,
      for a wide class of initial conditions the evolution of the system leads to the
      formation of a non-stationary irregular pattern corresponding to spatio-temporal
      chaos. The chaotic pattern first appears inside a sub-domain of the system. This
      sub-domain then steadily grows with time and, finally, the chaotic pattern
      invades the whole space, displacing the regular pattern.

PMID- 11302761
TI  - Analyzing radiation-induced complex chromosome rearrangements by combinatorial
      painting.
AB  - Cornforth, M. N. Analyzing Radiation-Induced Complex Chromosome Rearrangements by
      Combinatorial Painting. Radiat. Res. 155, 643-659 (2001). Prior to the advent of
      whole-chromosome painting, it was universally assumed that virtually all
      radiation-induced exchanges represented a simple rejoining between pairs of
      chromosome breaks. It is now known that a substantial proportion of such
      exchanges are actually complex, meaning that they involve the interaction of
      three (or more) breaks distributed among two (or more) chromosomes. The purpose
      of this review is to discuss some of the implications of aberration analysis
      using whole-chromosome painting, with emphasis given to newer combinatorial
      painting schemes that allow for the unambiguous identification of all homologous
      chromosome pairs. Such analysis requires reconsideration of how resulting
      information is to be handled for the purposes of tabulating and communicating raw
      data, quantifying aberration yields, and presenting experimental results in a
      cogent manner. Facilitating these objectives requires the introduction of certain
      concepts and terminologies that have no counterpart in conventional cytogenetic
      analyses.

PMID- 11302762
TI  - Complex chromosome exchanges induced by gamma rays in human lymphocytes: an mFISH
      study.
AB  - Loucas, B. D. and Cornforth, M. N. Complex Chromosome Exchanges Induced by Gamma
      Rays in Human Lymphocytes: An mFISH Study. Radiat. Res. 155, 660-671 (2001).
      Combinatorial multi-fluor fluorescence in situ hybridization (mFISH) allows the
      simultaneous painting of each pair of homologous chromosomes, thereby eliminating
      many of the difficulties previously associated with the analysis of complex
      rearrangements. We employed mFISH to visualize exchanges in human lymphocytes and
      found significant frequencies of these aberrations after gamma-ray doses of 2 and
      4 Gy. At 4 Gy, roughly half of the cells contained at least one complex exchange
      that required anywhere from 3 to 11 initial chromosome breaks. At this dose, more
      than 40% of gross cytogenetic damage, as measured by the total number of exchange
      breakpoints, was complex in origin. Both simple and complex exchanges were found
      to have nonlinear dose responses, although the latter showed significantly more
      upward curvature. In many cases, it could be deduced that the initial breaks
      leading to a particular complex exchange were proximate, meaning that the
      resulting broken chromosome ends all must have been capable of interacting freely
      during the exchange process. For other complex exchanges, the rearrangement could
      just as well have resulted from two or more simpler exchanges that occurred
      sequentially. The results demonstrate the utility of mFISH in visualizing
      intricacies of the exchange process, but also highlight the various sources of
      ambiguity concerning cytogenetic analysis that remain despite the power of this
      approach.

PMID- 11302763
TI  - RPA foci are associated with cell death after irradiation.
AB  - MacPhail, S. H. and Olive, P. L. RPA Foci are Associated with Cell Death after
      Irradiation. Radiat. Res. 155, 672-679 (2001). Complexes containing replication
      protein A (RPA) were observed in human TK6 and WIL-2NS lymphoblast cells and SiHa
      cervical carcinoma cells exposed to 250 kV X rays. Image analysis of individual
      cells with fluorescence-tagged anti-RPA antibodies was used to measure numbers of
      discrete foci per cell. RPA foci formed in S-phase cells in response to radiation
      doses as low as 0.5 Gy, and the number of foci/nucleus was linearly related to
      dose up to 50 Gy. The maximum number of cells with foci occurred 4-8 h after
      exposure to 4 Gy, and subsequently declined. However, the number of RPA foci per
      nucleus (in those cells with foci) reached a maximum after 2-4 h. Apoptotic
      nuclei from irradiated TK6 and WIL-2NS cells initially contained foci, but these
      were lost as degradation continued. Radiation-induced micronuclei in SiHa cells
      were greatly enriched for RPA foci, and cells with nuclei without foci often
      contained micronuclei with multiple RPA foci. In SiHa cells examined up to 7 days
      after 4 Gy, RPA foci reappeared in one or more cells in up to 90% of the
      surviving colonies, and some cells contained 150 or more distinct foci.
      Reappearance of these complexes could be indicative of radiation-induced genomic
      instability. These results are consistent with the idea that RPA foci observed
      several hours after irradiation represent irreparable lesions and as such might
      be useful in identifying radiosensitive cells.

PMID- 11302764
TI  - Requirement for repair of DNA double-strand breaks by homologous recombination in
      split-dose recovery.
AB  - Utsumi, H., Tano, K., Takata, M., Takeda, S. and Elkind, M. M. Requirement for
      Repair of DNA Double-Strand Breaks by Homologous Recombination in Split-Dose
      Recovery. Radiat. Res. 155, 680-686 (2001). Split-dose recovery has been observed
      under a variety of experimental conditions in many cell systems and is believed
      to be the result of the repair of sublethal damage. It is considered to be one of
      the most widespread and important cellular responses in clinical radiotherapy. To
      study the molecular mechanism(s) of this repair, we analyzed the knockout mutants
      KU70-/-, RAD54-/-, and KU70-/-/RAD54-/- of the chicken B-cell line, DT40. RAD54
      participates in the recombinational repair of DNA double-strand breaks (DSBs),
      while members of the KU family of proteins are involved in nonhomologous end
      joining. Split-dose recovery was observed in the parent DT40 and the KU70-/-
      cells. Moreover, the split-dose survival enhancement had all of the
      characteristics demonstrated earlier for the repair of sublethal damage, e.g.,
      the reappearance of the shoulder on the survival curve with dose fractionation;
      cyclic fluctuation in cell survival at 37 degrees C; repair and no cyclic
      fluctuation at 25 degrees C. These results strongly suggest that repair of
      sublethal damage is due to DSB repair mediated by homologous recombination, and
      that these DNA DSBs constitute sublethal damage.

PMID- 11302765
TI  - Electron paramagnetic resonance evidence for a C3' sugar radical in crystalline
      d(CTCTCGAGAG) X-irradiated at 4 K.
AB  - Debije, M. G. and Bernhard, W. A. Electron Paramagnetic Resonance Evidence for a
      C3' Sugar Radical in Crystalline d(CTCTCGAGAG) X-Irradiated at 4 K. Radiat. Res.
      155, 687-692 (2001). A neutral sugar radical formed by the net loss of hydrogen
      from C3' has been identified in crystalline DNA X-irradiated at 4 K. Crystals of
      duplex d(CTCTCGAGAG), known to be of B conformation, were studied using electron
      paramagnetic resonance (EPR) spectroscopy. The C3' radical was identified by
      using information from dose saturation, power saturation, thermal annealing, and
      spectrum simulation. The yield of the C3' radical, G(C3'), is 0.03 +/- 0.01
      micromol/J, and its concentration does not appear to saturate up to at least 100
      kGy. In the region in which total radical concentration increases linearly with
      dose, the C3' radical makes up about 4.5% of the total radical population trapped
      in the oligodeoxynucleotide crystal at 4 K. Based on free base release measured
      in other oligodeoxynucleotides, we suggest that in d(CTCTCGAGAG) the C3' radical
      is responsible for about one-third of the strand breakage events.

PMID- 11302766
TI  - Induction of telomerase activity by irradiation in human lymphoblasts.
AB  - Neuhof, D., Ruess, A., Wenz, F. and Weber, K. J. Induction of Telomerase Activity
      by Irradiation in Human Lymphoblasts. Radiat. Res. 155, 693-697 (2001).
      Telomerase activity is a radiation-inducible function, which suggests a role of
      this enzyme in DNA damage processing. Since the tumor suppressor TP53 plays a
      central role in the regulation of the cellular response to DNA damage, our study
      explored the ability of ionizing radiation to change telomerase activity and
      telomere length in two closely related human lymphoblast cell lines with
      different TP53 status. TK6 cells (wild-type TP53) and WTK1 cells (mutated TP53)
      were exposed to different doses of X rays, and telomerase activity was measured
      by PCR ELISA at different times after irradiation. A dose-dependent increase in
      telomerase activity was observed. One hour after irradiation with 4 Gy, TK6 and
      WTK1 cells showed an approximately 2.5-fold increase; for lower doses (0.1 to 1
      Gy), telomerase induction was seen only in TK6 cells. Telomerase induction was
      observed by 0.5 h after irradiation, with a further increase up to 24 h.
      Irradiated TK6 and WTK1 cells had longer telomeres (+1.3 kb) than unirradiated
      cells 14 days after exposure. Our data demonstrate a dose-dependent induction of
      telomerase activity and lengthening of telomeres by ionizing radiation in human
      lymphoblasts. Induction of telomerase activity by radiation does not generally
      appear to be controlled by the TP53-dependent DNA damage response pathway.
      However, for low doses, induction of telomerase requires wild-type TP53.

PMID- 11302767
TI  - A microdosimetric-kinetic model for the sensitization of v79 cells to radiation
      by incorporation of bromodeoxyuridine.
AB  - Hawkins, R. B. A Microdosimetric-Kinetic Model for the Sensitization of V79 Cells
      to Radiation by Incorporation of Bromodeoxyuridine. Radiat. Res. 155, 698-702
      (2001). The sensitization of G(1)-phase V79 cells to killing by ionizing
      radiation through incorporation of bromodeoxyuridine (BrdU) in their DNA has been
      reported to occur exclusively through an increase in the value of the quadratic
      parameter of the linear-quadratic survival relationship (beta) with no change in
      the linear parameter (alpha). The consequence of this, as understood through the
      microdosimetric-kinetic model of cell survival, is discussed. It is shown that
      the invariance of alpha implies that sensitization is due solely to a decrease in
      the rate of repair of the initial (potentially lethal) lesions in DNA containing
      BrdU. Further, for alpha to be unchanged, the average size of the compartments
      into which the nucleus is partitioned (domains), as postulated in the
      microdosimetric-kinetic model, must vary in proportion to the reciprocal of the
      square root of the rate constant for repair of the DNA lesions. This implies that
      the domain is not a structural subunit of the nucleus. It is a surrogate
      representation of the consequence of lesions in DNA being restricted to a region
      in the vicinity of the location in the nucleus at which they are created. A
      lesion is confined because the distance it can diffuse by random flight to react
      with another lesion to form a lethal lesion is restricted because a lesion's
      lifetime is limited by the repair process.

PMID- 11302768
TI  - Simulation of exon deletion mutations induced by low-LET radiation at the HPRT
      locus.
AB  - Friedland, W., Li, W. B., Jacob, P. and Paretzke, H. G. Simulation of Exon
      Deletion Mutations Induced by Low-LET Radiation at the HPRT Locus. Radiat. Res.
      155, 703-715 (2001). The induction of HPRT mutants with exon deletions after
      irradiation with photons was simulated using the biophysical radiation track
      structure model PARTRAC. The exon-intron structure of the human HPRT gene was
      incorporated into the chromatin fiber model in PARTRAC. After gamma and X
      irradiation, simulated double-stranded DNA fragments that overlapped with exons
      were assumed to result in exon deletion mutations with a probability that
      depended on the genomic or the geometric distance between the breakpoints. The
      consequences of different assumptions about this probability of deletion
      formation were evaluated on the basis of the resulting fractions of total,
      terminal and intragenic deletions. Agreement with corresponding measurements was
      obtained assuming a constant probability of deletion formation for fragments
      smaller than about 0.1 Mbp, and a probability of deletion formation decreasing
      with increasing geometric or genomic distance between the end points for larger
      fragments. For these two assumptions, yields of mutants with exon deletions, size
      distributions of deletions, patterns of deleted exons, and patterns of deleted
      STS marker sites surrounding the gene were calculated and compared with
      experimental data. The yields, size distributions and exon deletion patterns were
      grossly consistent, whereas larger deviations were found for the STS marker
      deletion patterns in this comparison.

PMID- 11302769
TI  - The use of radiation-induced bacterial promoters in anaerobic conditions: a means
      to control gene expression in clostridium-mediated therapy for cancer.
AB  - Nuyts, S., Van Mellaert, L., Theys, J., Landuyt, W., Lambin, P. and Anne, J. The
      Use of Radiation-Induced Bacterial Promoters in Anaerobic Conditions: A Means to
      Control Gene Expression in Clostridium-Mediated Therapy for Cancer. Radiat. Res.
      155, 716-723 (2001). Apathogenic clostridia, which have been genetically
      engineered to express therapeutic genes, will specifically target hypoxic and
      necrotic regions in tumors. This specificity can be improved further if the
      expression of these genes is controlled by a radiation-induced promoter, leading
      to spatial and temporal control of gene expression. We isolated two radiation
      inducible genes of the SOS repair system of Clostridium. Northern blot
      experiments confirmed radiation activation of the recA and recN genes at a dose
      of 2 Gy. The promoter region of these genes was isolated and used to regulate
      expression of the lacZ gene under anaerobic conditions. For the recA promoter, a
      significant increase of beta-galactosidase activity of 20-30% was seen after 2 Gy
      irradiation. The recN promoter did not show a significant induction and had a 50
      100 times lower basal expression. Treatment of the recombinant clostridial
      cultures with the cytostatic agent mitomycin C also resulted in a significant
      increase of beta-galactosidase activity that was under the control of recA or
      recN promoter. Oxygen does not appear to be necessary in the activation of the
      SOS repair system by irradiation as tested with Escherichia coli since recA
      deficient and recA-containing strains showed similar survival after treatment
      with UV and ionizing radiation in the presence or absence of oxygen.

PMID- 11302770
TI  - Effects of the interaction between carbogen and nicotinamide on R3230 Ac tumor
      blood flow in Fischer 344 rats.
AB  - Braun, R. D., Lanzen, J. L., Turnage, J. A., Rosner, G. and Dewhirst, M. W.
      Effects of the Interaction between Carbogen and Nicotinamide on R3230 Ac Tumor
      Blood Flow in Fischer 344 Rats. Radiat. Res. 155, 724-733 (2001). The purpose of
      this study was to determine whether there are interactions between carbogen
      breathing and various doses of nicotinamide at the level of the tumor arteriole
      that might contribute to the improvement in tumor blood flow and pO(2) that is
      often seen with this combination treatment. R3230 adenocarcinomas were implanted
      and grown to 4-5 mm in dorsal skin flap window chambers in F344 rats. Saline or
      65, 200 or 500 mg/kg nicotinamide was injected i.p. while the rat breathed air
      through a face mask. After 20 min, either the breathing gas was switched to
      carbogen for 60 min or the animal remained on air. Measured end points included
      diameter of tumor arterioles, tumor perfusion, mean arterial blood pressure, and
      heart rate. None of the measured parameters were affected by injection of saline
      or nicotinamide, except at the highest nicotinamide dose (500 mg/kg). Mean
      arterial blood pressure showed a median decrease of 25% when 500 mg/kg
      nicotinamide was given. Diameter of tumor arterioles decreased significantly from
      5-15 min after 500 mg/kg nicotinamide was given but was back to baseline by 20
      min. Blood flow decreased significantly 5-20 min after administration of 500
      mg/kg nicotinamide compared to the baseline prior to injection. Carbogen
      breathing resulted in a small increase in mean arterial blood pressure in all
      groups. There was a transient decrease in the diameter of tumor arterioles and
      blood flow during the first 5 min of carbogen breathing that was statistically
      significant in several groups. In the group injected with 500 mg/kg nicotinamide,
      the diameter of tumor arterioles increased by about 10% during the first 25 min
      of carbogen breathing, and blood flow increased by a median of 75% over the level
      prior to carbogen breathing up to 40 min after carbogen breathing. The increase
      in flow in this group was most likely caused by the concomitant arteriolar
      vasodilation. Thus there was direct evidence for an interaction between carbogen
      breathing and nicotinamide, but only at the dose of 500 mg/kg nicotinamide. Since
      this dose yields plasma levels of nicotinamide that are higher than can be
      tolerated clinically, it is uncertain whether these changes in arteriolar
      diameter and blood flow would occur in human tumors.

PMID- 11302771
TI  - Induction of heme oxygenase 1 in radiation nephropathy: role of angiotensin II.
AB  - Datta, P. K., Moulder, J. E., Fish, B. L., Cohen, E. P. and Lianos, E. A.
      Induction of Heme Oxygenase 1 in Radiation Nephropathy: Role of Angiotensin II.
      Radiat. Res. 155, 734-739 (2001). In a rat model of radiation-induced
      nephropathy, we investigated changes in expression of heme oxygenase 1 (Hmox1,
      also known as HO-1), an enzyme that catalyzes conversion of heme into biliverdin,
      carbon monoxide and iron. The study explored whether radiation induces Hmox1
      expression in the irradiated kidney and whether angiotensin II (AII) mediates
      Hmox1 expression in glomeruli isolated from irradiated kidneys. To assess the
      effects of radiation on Hmox1 expression, rats received 20 Gy bilateral renal
      irradiation and were randomized to groups receiving an AII type 1 (AT(1))
      receptor antagonist (L-158,809) or no treatment. Drug treatment began 9 days
      prior to bilateral renal irradiation and continued for the duration of the study.
      Estimation of Hmox1 levels in glomerular protein lysates assessed by Western blot
      analysis revealed a significant increase in Hmox1 protein at 50 and 65 days
      postirradiation. In animals treated with the AT(1) receptor antagonist, there was
      no induction of Hmox1, suggesting that AII may be a mediator of Hmox1 induction.
      To confirm that AII stimulates Hmox1 expression, animals were infused with 200,
      400 or 800 ng/kg min(-1) of AII for 18-19 days, and Hmox1 protein levels in
      glomeruli were assessed. There was a significant induction of Hmox1 in glomeruli
      of animals infused with 800 ng/kg min(-1) of AII. These studies demonstrate that
      glomerular Hmox1 expression is elevated in the middle phase of radiation
      nephropathy and that AII can increase glomerular Hmox1 levels.

PMID- 11302772
TI  - Meta-analysis of increases in micronuclei in peripheral blood lymphocytes after
      angiography or excretory urography.
AB  - Norman, A., Cochran, S. T. and Sayre, J. W. Meta-analysis of Increases in
      Micronuclei in Peripheral Blood Lymphocytes after Angiography or Excretory
      Urography. Radiat. Res. 155, 740-743 (2001). Meta-analysis of 10 studies confirms
      a significant increase in the frequency of micronuclei in peripheral blood
      lymphocytes after angiography or excretory urography; the weighted average
      increase is 4.2 (95% confidence interval 2.8-5.6) per 1000 binucleate
      lymphocytes, about the same increase in micronuclei as that produced in vitro by
      a diagnostic X-ray dose of 4 cGy. The analysis failed to reveal a significant
      effect of the specific contrast medium used in the X-ray examinations on the
      increased frequency of micronuclei. These results are consistent with the
      hypothesis that the effect of the contrast media is limited to the enhancement,
      by the photoelectric effect, of the X-ray dose absorbed by the lymphocytes
      irradiated while suspended in the contrast medium. Therefore, an estimate of
      increased cancer risk based on elevated frequencies of micronuclei or chromosome
      aberrations in peripheral blood lymphocytes may be greatly exaggerated whenever
      the radiation damage is largely confined to the cells circulating in the blood,
      as it is in people who have recently had X-ray examinations that use intravenous
      injections of contrast medium. Such examinations include angiography, excretory
      urography and CT scans, which are received annually by millions of people.

PMID- 11302773
TI  - Detection of elevated RBE in human lymphocytes exposed to secondary electrons
      released from X-irradiated metal surfaces.
AB  - Regulla, D., Panzer, W., Schmid, E., Stephan, G. and Harder, D. Detection of
      Elevated RBE in Human Lymphocytes Exposed to Secondary Electrons Released from X
      Irradiated Metal Surfaces. Radiat. Res. 155, 744-747 (2001). Monolayers of human
      lymphocytes, attached to a 2-microm Mylar film, were irradiated with 60 kV X rays
      in the presence and absence of a 150-microm gold film backing the Mylar film.
      With the gold film present, the absorbed dose imparted to the cells was increased
      by a factor of 45.4 due to the release of photoelectrons from the gold film. The
      frequencies of dicentric chromosomes and centric rings as well as of excess
      acentric fragments were increased in agreement with this dose enhancement, and in
      addition an RBE of about 1.7 compared to the frequencies observed in the absence
      of the gold film was found. These radiation effects, which contribute to risk
      considerations in radiology, are interpreted in terms of the increased dose-mean
      restricted LET of the photoelectrons backscattered from the metal and slowed down
      in the Mylar film before they enter the cell layer.

PMID- 11302774
TI  - Prolonged effects of acute gamma irradiation on acetylcholine-induced potassium
      currents in human umbilical vein endothelial cells.
AB  - Bourlier, V., Diserbo, M., Gourmelon, P. and Verdetti, J. Prolonged Effects of
      Acute Gamma Irradiation on Acetylcholine-Induced Potassium Currents in Human
      Umbilical Vein Endothelial Cells. Radiat. Res. 155, 748-752 (2001). We have
      recently reported an acute effect of gamma irradiation (15 Gy, 1 Gy/min) on
      acetylcholine-mediated endothelium-dependent relaxation in rat aortic rings.
      Given the importance of permeability to K+ to endothelium-dependent relaxation,
      we have evaluated the effect of the same radiation on K+ currents in human
      endothelial cells in culture using the patch-clamp technique in the whole-cell
      recording configuration. Our results indicate that, in resting cells, gamma
      irradiation has no effect on endothelial permeability to K+. However, irradiation
      during stimulation of endothelial cells with acetylcholine reduces the sustained
      increase in permeability to K+ observed in the acetylcholine-stimulated,
      nonirradiated cells. Additional experiments using K+ channel inhibitors (TEA,
      charybdotoxin, apamin) suggest that irradiation may in part decrease the
      prolonged activation of Ca2+-activated K+ channels by acetylcholine. Taken
      together with our previous finding that irradiation inhibits the acute relaxing
      effects of acetylcholine, these results show that gamma irradiation also affects
      the delayed effects of acetylcholine on permeability to K+.

PMID- 11302775
TI  - In memoriam: Ugo Fano (1912-2001).

PMID- 11302777
TI  - Analyze that feces before you throw it into the fan.

PMID- 11302778
TI  - Hemorrhoids and varicose veins: a review of treatment options.
AB  - Hemorrhoids and varicose veins are common conditions seen by general
      practitioners. Both conditions have several treatment modalities for the
      physician to choose from. Varicose veins are treated with mechanical compression
      stockings. There are several over-the-counter topical agents available for
      hemorrhoids. Conservative therapies for both conditions include diet, lifestyle
      changes, and hydrotherapy which require a high degree of patient compliance to be
      effective. When conservative hemorrhoid therapy is ineffective, many physicians
      may choose other non-surgical modalities: injection sclerotherapy, cryotherapy,
      manual dilation of the anus, infrared photocoagulation, bipolar diathermy, direct
      current electrocoagulation, or rubber band ligation. Injection sclerotherapy is
      the non-surgical treatment for primary varicose veins. Non-surgical modalities
      require physicians to be specially trained, own specialized equipment, and assume
      associated risks. If a non-surgical approach fails, the patient is often referred
      to a surgeon. The costly and uncomfortable nature of treatment options often lead
      a patient to postpone evaluation until aggressive intervention is necessary. Oral
      dietary supplementation is an attractive addition to the traditional treatment of
      hemorrhoids and varicose veins. The loss of vascular integrity is associated with
      the pathogenesis of both hemorrhoids and varicose veins. Several botanical
      extracts have been shown to improve microcirculation, capillary flow, and
      vascular tone, and to strengthen the connective tissue of the perivascular
      amorphous substrate. Oral supplementation with Aesculus hippocastanum, Ruscus
      aculeatus, Centella asiatica, Hamamelis virginiana, and bioflavonoids may prevent
      time-consuming, painful, and expensive complications of varicose veins and
      hemorrhoids.

PMID- 11302779
TI  - Natural therapies for ocular disorders, part two: cataracts and glaucoma.
AB  - Pathophysiological mechanisms of cataract formation include deficient glutathione
      levels contributing to a faulty antioxidant defense system within the lens of the
      eye. Nutrients to increase glutathione levels and activity include lipoic acid,
      vitamins E and C, and selenium. Cataract patients also tend to be deficient in
      vitamin A and the carotenes, lutein and zeaxanthin. The B vitamin riboflavin
      appears to play an essential role as a precursor to flavin adenine dinucleotide
      (FAD), a co-factor for glutathione reductase activity. Other nutrients and
      botanicals, which may benefit cataract patients or help prevent cataracts,
      include pantethine, folic acid, melatonin, and bilberry. Diabetic cataracts are
      caused by an elevation of polyols within the lens of the eye catalyzed by the
      enzyme aldose reductase. Flavonoids, particularly quercetin and its derivatives,
      are potent inhibitors of aldose reductase. Glaucoma is characterized by increased
      intraocular pressure (IOP) in some but not all cases. Some patients with glaucoma
      have normal IOP but poor circulation, resulting in damage to the optic nerve.
      Faulty glycosaminoglycan (GAG) synthesis or breakdown in the trabecular meshwork
      associated with aqueous outflow has also been implicated. Similar to patients
      with cataracts, those with glaucoma typically have compromised antioxidant
      defense systems as well. Nutrients that can impact GAGs such as vitamin C and
      glucosamine sulfate may hold promise for glaucoma treatment. Vitamin C in high
      doses has been found to lower IOP via its osmotic effect. Other nutrients holding
      some potential benefit for glaucoma include lipoic acid, vitamin B12, magnesium,
      and melatonin. Botanicals may offer some therapeutic potential. Ginkgo biloba
      increases circulation to the optic nerve; forskolin (an extract from Coleus
      forskohlii) has been used successfully as a topical agent to lower IOP; and
      intramuscular injections of Salvia miltiorrhiza have shown benefit in improving
      visual acuity and peripheral vision in people with glaucoma.

PMID- 11302780
TI  - Natural agents in the prevention of cancer, part two: preclinical data and
      chemoprevention for common cancers.
AB  - This paper is the second of a series examining the use of nutritional supplements
      as chemopreventive agents. The animal and in vitro data are reviewed in support
      of their use. Human safety data and mechanisms of action are described as well.
      Many over-the-counter dietary supplements have been shown to have significant
      chemopreventive activity in preclinical studies. Few side effects are associated
      with even long-term use of these agents. Along with dietary and lifestyle risk
      reducing strategies, nutritional supplementation appears to be a viable
      intervention for those considered to be at high risk of developing cancer.

PMID- 11302781
TI  - Clinical outcomes of a diagnostic and treatment protocol in allergy/sensitivity
      patients.
AB  - OBJECTIVES: This level II outcome study was conducted to examine the efficacy and
      toxicity of a diagnostic and treatment protocol using electrodermal screening
      (EDS) in allergy/sensitivity patients. METHODS: Ninety-six patients with a
      diagnosis of allergy or sensitivity entered the study between 1994 and 1998; 90
      participants completed the study. All participants followed the same protocol,
      and all interactions were with a single clinician at a single site. The Allergy
      Symptom Severity Index (ASSI) was developed to record symptomatic information.
      EDS - conductance measurement 1/( - of specific acupuncture points was used as an
      objective endpoint (indicator of outcome) and for identification of antigens,
      according to Voll criteria. All measurements were taken before and after
      treatment, and EDS was carried out at all treatment sessions. Outcome criteria
      suggesting efficacy were reduction in ASSI score, reduction in number of items
      testing positive, and normalization of conductance measurements. A statistical
      analysis of the outcomes was performed using the student's paired t-test.
      RESULTS: There was a statistically significant change in pre- and post-treatment
      measurements of the ASSI. The conductance measurements normalized and the number
      of items testing positive decreased compared to pre-treatment testing. In
      addition to these parameters, 87.2 percent of subjects rated efficacy as good to
      excellent, and less than one-percent rated the outcome as poor. The outcome
      demonstrated longevity, meaning that people who had their post-treatment
      evaluation up to three years after primary treatment were still showing minimal
      ASSI scores, with no additional treatment. The treatment appeared to work equally
      well across age groups and gender. Forty-eight percent of participants had an
      aggravation of symptoms after treatment, lasting an average of 10 hours, with
      reactions described as mild to moderate. Average cost of the desensitization
      protocol (all costs included) was $822.16. CONCLUSIONS: This protocol
      demonstrated efficacy without serious toxicity and no long-term adverse effects.
      It is natural, non-invasive, and does not require long periods of avoidance of
      offending foods or environmental stimuli. The desensitization protocol is a low
      cost, effective therapy for the treatment of patients suffering from symptoms of
      allergy/sensitivity disease.

PMID- 11302782
TI  - Monograph. Plant sterols and sterolins.
AB  - Sterols and sterolins, also known as phytosterols, are fats present in all
      plants, including fruits and vegetables. Although they are chemically similar to
      the animal fat, cholesterol, they have been shown to exert significant unique
      biochemical effects in both animals and humans. Because they are bound to the
      fibers of the plant, they are difficult to absorb during the transit of digested
      food through the gut, particularly in individuals with impaired digestive
      function. For this reason, and because much of the modern diet is over-processed
      and low in fresh plant materials, sterols and sterolins appear in the serum and
      tissue of healthy humans at 800-1000 times lower concentrations than that of
      cholesterol. Beta-sitosterol (BSS) is the major phytosterol in higher plants
      along with its glycoside, beta-sitosterolin (BSSG). Animal studies have
      demonstrated BSS and BSSG possess anti-inflammatory, antipyretic, antineoplastic,
      and immune-modulating properties. In other in vitro, animal, and human studies, a
      proprietary BSS:BSSG mixture has shown promise in normalizing T-cell function,
      dampening overactive antibody responses, and normalizing DHEA:cortisol ratios.
      Research has shown plant oils contain the highest concentration of phytosterols,
      nuts and seeds contain moderate amounts, and fruits and vegetables generally
      contain the lowest phytosterol concentrations. Because only low levels of these
      substances are found in humans, increased dietary intake of unprocessed fruits
      and vegetables or supplementation with commercial phytosterols may be of benefit
      in re-establishing optimal immune parameters. Restoring balance to the immune
      system may be of therapeutic benefit in disease processes such as chronic viral
      infections, stress-induced immune suppression, tuberculosis, allergies, cancer,
      and rheumatoid arthritis and other autoimmune conditions.

PMID- 11302783
TI  - Monograph. Petasites hybridus.
AB  - Petasides hybridus (butterbur) is a perennial shrub, found throughout Europe as
      well as parts of Asia and North America, that has been used medicinally for
      centuries. During the Middle Ages butterbur was used to treat plague and fever;
      in the 17th century its use was noted in treating cough, asthma, and skin wounds.
      The plant can grow to a height of three feet and is usually found in wet, marshy
      ground, in damp forests, and adjacent to rivers or streams. Its downy leaves can
      attain a diameter of three feet, making it the largest of all indigenous floras,
      and their unique characteristics are responsible for the plant's botanical and
      common names. The genus name, Petasites, is derived from the Greek word petasos,
      which is the felt hat worn by shepherds. The common name of butterbur is
      attributed to the large leaves being used to wrap butter during warm weather.
      Other common names include pestwurz (German), blatterdock, bog rhubarb, and
      butter-dock. Currently, the primary therapeutic uses for butterbur are for
      prophylactic treatment of migraines, and as an anti-spasmodic agent for chronic
      cough or asthma. It has also been used successfully in preventing gastric ulcers,
      and in treating patients with irritable bladder and urinary tract spasms.

PMID- 11302784
TI  - Pharmacokinetics of celecoxib in the presence and absence of interferon-induced
      acute inflammation in the rat: application of a novel HPLC assay.
AB  - PURPOSE: Celecoxib (CEL) is a relatively new cyclooxygenase-2 specific inhibitor
      nonsteroidal anti-inflammatory drug with low incidents of the toxic side effects.
      We developed and validated an HPLC assay for CEL and delineated pharmacokinetics
      of the drug in the rat in the presence and absence of inflammation. METHODS: Rat
      plasma (0.1 mL plasma) was spiked with CEL and ibuprofen as internal standard.
      The solution was acidified and constituents were extracted with isooctane
      isopropanol (95:5). The organic solvent was separated, evaporated and the residue
      was dissolved in the HPLC mobile phase [acetonitrile-water-acetic acid
      triethylamine (47:53:0.1:0.03)]. The HPLC system consisted of an auto-injector,
      an isocratic pump, a 10 cm C(18) analytical column packed with 5-microm of
      reversed-phase particles, a UV detector set at 254 nm, and an integrator. Control
      adult male Sprague-Dawley rats were dosed with CEL [5 mg/kg i.v. (n=8), p.o.
      (n=6) or i.p. (n=3)]. Acute inflammation was brought about by two (12 and 1 h pre
      CEL) s.c. injection of 50,000IU/200 microL interferonalpha2a. Inflamed rats (n=6)
      received 5 mg oral CEL. Serial blood samples were collected via a inserted
      catheter at the right jugular vein, and plasma samples were analyzed for CEL.
      RESULTS: The assay yielded linear response within the examined ranges of 20-1000
      ng/mL and 1-100 microg/mL (r(2)>0.99) with an extraction efficiency of >70%,
      intra- and inter-day variability of <10% and accuracy of >90%. In control rats,
      CEL had an oral bioavailability of 0.59 due mainly to presystemic hepatic
      metabolism. A multi-compartmental disposition kinetics with an average terminal
      t(1/2) of 2.8 +/- 0.7 h, and volume of distribution of 2.3 +/- 0.6 L/kg were
      found. Acute inflammation had no significant effect on the pharmacokinetics of
      CEL, although a trend towards increased plasma concentration was noticed.
      CONCLUSIONS: The validated assay has sufficient accuracy and precision for
      pharmacokinetic studies of CEL in the rat. The lack of change in CEL
      pharmacokinetics after acute inflammation maybe due to 1) insensitivity of its
      metabolic system to the acknowledged inhibitory effect of inflammation, and/or 2)
      the relatively low pre-systemic metabolism of the drug.

PMID- 11302785
TI  - Investigation of interpolymer complexation between Carbopol and various grades of
      polyvinylpyrrolidone and effects on adhesion strength and swelling properties.
AB  - PURPOSE: To investigate the interpolymer complexation between Carbopol 934P (CP)
      and various grades of polyvinylpyrrolidone (PVP) (K90, K32, C15, and VA/S-630).
      METHODS: Amount of fresh and dried CP-PVP complexes, water retaining capacity,
      apparent density, pH, conductivity, FTIR, swelling and adhesion strength were
      studied. RESULTS: Interpolymer complexation occurred between CP and all the PVP,
      but most significantly with PVP K90. Maximum amount of fresh and dried CP-PVP K32
      complexes were obtained at a weight ratio of 1:1. On the contrary, CP
      concentration was linearly related to amount of CP-PVP K90 complexes produced and
      their water retaining capacity were all above 97%. Increase in CP concentration
      caused a decrease in pH, but an increase in conductivity for all the CP-PVP
      complexes. The apparent density of the filtrate of CP-PVP K90 complex was the
      lowest and its IR spectrum was similar to that of pure PVP K90, indicating that
      all the CP has interacted with the PVP K90. Discs of physical mixtures of CP-PVP
      K90 swelled gradually and reached a maximum after 20-30 hr, while discs of solid
      complex swelled readily and reached a maximum within 20 hr. Adhesion strength was
      directly correlated to CP content. However, adhesion strength of solid CP-PVP K90
      complex was lower than the physical mixture of the pure polymers. CONCLUSION:
      Interpolymer complexation occurred between CP and PVP but to a different extent
      for the various grades of PVP. Complexation was most prominent between CP and PVP
      K90.

PMID- 11302786
TI  - In vitro investigation of the hepatic extraction of RSD1070, a novel
      antiarrhythmic compound.
AB  - PURPOSE: The hepatic extraction of a novel antiarrhythmic, RSD1070, was
      investigated to test the hypothesis that the poor bioavailability observed in
      rats is due to high hepatic metabolism. METHODS: The pharmacokinetics of RSD1070
      was examined in rats (n=8) and its metabolism was investigated using pooled rat
      hepatic microsomes. The free fraction in plasma and microsomal matrices was
      determined by equilibrium dialysis. Hepatic extraction was predicted by scaling
      up of the microsomal kinetic data using the well-stirred liver model. RESULTS:
      RSD1070 demonstrated tri-exponential decay following single iv bolus
      administration of a dose of 12 mg/kg. RSD1070 exhibited a rapid elimination, t1/2
      of 25 +/- 8 min and a CL(tot) of 71 +/- 9 mL/min/kg. Renal clearance based on 24
      h urinary recovery was determined to be insignificant (<< 1% of CL(tot)). A
      Michaelis-Menten model described the elimination of RSD1070 with a K(m) of 0.45
      microg/mL and Vmax of 2.81 microg/min/mg microsomal protein. Taking the
      V(max)/K(m) ratio (CL(int)) as the basis for scaling, the data from the
      microsomal kinetic studies (75 mL/min/kg) closely approximated the apparent
      CL(tot). In the scale-up of the in vitro CL(int), plasma free fraction (1.5%) and
      microsomal free fraction (15%) were determined and incorporated into the well
      stirred liver model. CONCLUSION: RSD1070 is a high hepatic extraction compound (E
      = 0.94) with a predicted CL(h) value that accounted for the CL(tot) observed in
      rats.

PMID- 11302787
TI  - A high-performance liquid chromatographic assay for the determination of
      desbutylhalofantrine enantiomers in rat plasma.
AB  - PURPOSE: To develop a stereoselective high performance liquid chromatographic
      assay for determination of desbutylhalofantrine (DHF) enantiomers in rat plasma.
      METHODS: After protein precipitation of 100 microL of rat plasma, racemic DHF and
      internal standard (quinidine sulfate) were extracted into hexane in the presence
      of pH 8 phosphate buffer. After transfer and evaporation of the hexane, the
      residue was derivatized using 0.25 M (+)-di-O-acetyl-L-tartaric acid anhydride at
      4 degrees C. After 5 min the reaction was stopped by addition of methanol in
      water, and the tube contents were dried, reconstituted in the mobile phase, and
      injected into a C(18) analytical column under reverse phase conditions. RESULTS:
      The derivatized enantiomers were baseline resolved and free of interference from
      endogenous components in plasma. Standard curves were linear (r(2)>0.99) over the
      range of enantiomer concentrations from 25-1000 ng/mL. The assay was validated to
      concentrations as low as 25 ng/mL, based on 100 microL of rat plasma. The nature
      of diastereomers formed was found to be dependent on the temperature used during
      the derivatization step. In a preliminary experiment in the rat,
      stereoselectivity in the plasma concentrations of DHF were observed, indicating
      stereoselectivity in the pharmacokinetics of the metabolite. CONCLUSIONS: The
      assay was sensitive and appropriate for use in pharmacokinetic studies of DHF in
      the rat.

PMID- 11302788
TI  - Molecular modeling of arginine-glycine-aspartic acid (RGD) analogs: relevance to
      transepithelial transport.
AB  - PURPOSE: The aim of this research is to model the effect of methylation on
      hydrogen bonding ability, surface area, polar surface area, volume,
      lipophilicity, charge, and cross-sectional diameters of a series of mono-, di-,
      and tri- methyl substituted analogs of arginine-glycine-aspartic acid (RGD) and
      compare these parameters to in vitro transport properties across Caco-2
      monolayers. METHODS: Molecular modeling was used to investigate the structural
      parameters that may influence the transport properties of RGD and its methyl
      analogs at pH 7.4. Log P was experimentally determined using a potentiometric
      method and compared to cLogP. Transport studies were carried out using Caco-2
      cell monolayers. RESULTS: Parameters such as polar and total surface area,
      volume, and Log P were found to vary with both the number and the sites of methyl
      substitution on the RGD molecule. The calculated as well as the experimental Log
      P values were found to be less than minus 2. The calculated maximum cross
      sectional diameters ranged from 9 to 12 A. No detectable transport was noted.
      CONCLUSIONS: Results of our study indicate that in the design considerations for
      the development of new peptidomimetic RGD analogs with enhanced oral
      bioavailability, an important parameter to consider is the three dimensional
      conformation of the peptides which influences their hydrogen bonding ability,
      polarity and molecular geometry.

PMID- 11302789
TI  - N6-cyclohexyladenosine and 3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic
      acid enhance the effect of antiepileptic drugs against induced seizures in mice.
AB  - PURPOSE: The influence of N(6)-Cyclohexyladenosine (CHA), an adenosine A(1)
      agonist and 3-(2-Carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid (CPPene), a
      selective N-methyl-D-aspartate (NMDA) antagonist upon the anticonvulsant activity
      of diazepam (DA), sodium valproate (VP), diphenylhydantoin (DPH), phenobarbital
      (PB) and carbamazepine (CAZ) was investigated in mice. All agents were
      administered intraperitoneally. METHODS: Convulsive seizures were induced by the
      use of electro shocks and pentylenetetrazole (PTZ). RESULTS: CHA (2 mg/kg, i.p.)
      and CPPene (2.5 mg/kg, i.p.) were found to enhance the anticonvulsant activity of
      the tested antiepileptic drugs against both electro convulsions and PTZ-induced
      convulsions. Both CHA and CPPene significantly decreased the ED50 values of these
      drugs against both electro convulsions and PTZ-induced convulsions, and increased
      the convulsive threshold. CHA (2 mg/kg, i.p.) and CPPene (2.5 mg/kg, i.p.) did
      not affect the plasma level of any of the tested antiepileptic drugs, indicating
      no pharmacokinetic interactions at the systemic administration. CHA (2 mg/kg,
      i.p.) or CPPene (2.5 mg/kg, i.p.), alone or in combination with the tested
      antiepileptic drugs produced no significant changes in their effects on the heart
      rate, blood pressure, body temperature, gross behavior or on the locomotor
      activity of experimental animals. Combinations of the antiepileptic drugs with
      CHA (2 mg/kg, i.p.) or CPPene (2.5 mg/kg, i.p.) were also devoid of significant
      effects on the motor performance and long-term memory in mice demonstrated by the
      Chimney test and passive avoidance task. CHA (5 mg/kg, i.p.) alone or in
      combination with the tested antiepileptic drugs produced inhibition of locomotor
      activity and motor coordination, sedation and hypothermia as well as impairing of
      long-term memory. CONCLUSION: Adenosine A1 agonists and NMDA antagonists enhance
      the efficacy of common antiepileptic drugs, indicating the involvement of
      adenosine and NMDA receptors in the convulsive pathway. The potential therapeutic
      benefits of such interactions may be taken into consideration and merit further
      investigations in animals and humans.

PMID- 11302790
TI  - Screening system for xenosiderophores as potential drug delivery agents in
      mycobacteria.
AB  - In order to establish a screening system for xenosiderophores which can be
      utilized by mycobacteria, we generated a set of mutants of Mycobacterium
      smegmatis that are blocked in different steps of the well-known iron acquisition
      system. One mutant with a block in mycobactin biosynthesis was generated from
      strain mc(2)155 by chemical mutagenesis. The exochelin biosynthesis gene fxbA and
      the ferric exochelin uptake gene fxuA, previously identified by Fiss et al. (E.
      H. Fiss, S. Yu, and W. R. Jacobs, Jr., Mol. Microbiol. 14:557-559, 1994), were
      knocked out by gene replacement. Adjacent chromosomal fragments were used for
      homologous recombination in order to replace wild-type genes by the kanamycin
      resistance gene from transposon Tn903. Gene replacement was confirmed by PCR. The
      isolated mutants show the expected phenotype: fxbA mutants are defective in
      exochelin biosynthesis, whereas fxuA mutants excrete a significantly larger
      amount of exochelin compared to the amount excreted by the parent strain. This is
      due to their defectiveness in ferriexochelin uptake, as demonstrated in growth
      promotion assays. This new set of mutants allows differentiation of siderophores
      that supply mycobacteria with iron by ligand exchange with exochelin or
      mycobactin, by the use of separate siderophore uptake routes, or by the use of
      the exochelin permease. All these types of iron uptake routes were identified
      with 25 exogenous siderophores as test substances. Siderophores that act without
      ligand exchange are potential candidates as drug vectors that can be used to
      overcome permeability-mediated resistance.

PMID- 11302791
TI  - Structural comparison of three types of staphylococcal cassette chromosome mec
      integrated in the chromosome in methicillin-resistant Staphylococcus aureus.
AB  - The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a
      novel mobile genetic element, designated staphylococcal cassette chromosome mec
      (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S.
      aureus (MRSA) strain. We now report identification of two additional types of
      mecA-carrying genetic elements found in the MRSA strains isolated in other
      countries of the world. There were substantial differences in the size and
      nucleotide sequences between the elements and the SCCmec. However, new elements
      shared the chromosomal integration site with the SCCmec. Structural analysis of
      the new elements revealed that they possessed all of the salient features of the
      SCCmec: conserved terminal inverted repeats and direct repeats at the integration
      junction points, conserved genetic organization around the mecA gene, and the
      presence of cassette chromosome recombinase (ccr) genes responsible for the
      movements of SCCmec. The elements, therefore, were considered to comprise the
      SCCmec family of staphylococcal mobile genetic elements together with the
      previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20
      countries, 34 were shown to possess one of the three typical SCCmec elements on
      the chromosome. Our findings indicated that there are at least three distinct
      MRSA clones in the world with different types of SCCmec in their chromosome.

PMID- 11302792
TI  - Synergy of histone-derived peptides of coho salmon with lysozyme and flounder
      pleurocidin.
AB  - Recent research has identified endogenous cationic antimicrobial peptides as
      important factors in the innate immunity of many organisms, including fish. It is
      known that antimicrobial activity, as well as lysozyme activity, can be induced
      in coho salmon (Oncorhynchus kisutch) mucus after exposure of the fish to
      infectious agents. Since lysozyme alone does not have antimicrobial activity
      against Vibrio anguillarum and Aeromonas salmonicida, a four-step protein
      purification protocol was used to isolate and identify antibacterial fractions
      from bacterially challenged coho salmon mucus and blood. The purification
      consisted of extraction with hot acetic acid, extraction and concentration on a
      C(18) cartridge, gel filtration, and reverse-phase chromatography on a C(18)
      column. N-terminal amino acid sequence analyses revealed that both the blood and
      the mucus antimicrobial fractions demonstrated identity with the N terminus of
      trout H1 histone. Mass spectroscopic analysis indicated the presence of the
      entire histone, as well as fragments thereof, including a 26-amino-acid N
      terminal segment. These fractions inhibited the growth of antibiotic
      supersuscptible Salmonella enterica serovar Typhimurium, as well as A.
      salmonicida and V. anguillarum. Synthetic peptides identical to the N-terminally
      acetylated or C-terminally amidated 26-amino-acid fragment were inactive in
      antimicrobial assays, but they potentiated the antimicrobial activities of the
      flounder peptide pleurocidin, lysozyme, and crude lysozyme-containing extracts
      from coho salmon. The peptides bound specifically to anionic lipid monolayers.
      However, synergy with pleurocidin did not appear to occur at the cell membrane
      level. The synergistic activities of inducible histone peptides indicate that
      they play an important role in the first line of salmon defenses against
      infectious pathogens and that while some histone fragments may have direct
      antimicrobial effects, others improve existing defenses.

PMID- 11302793
TI  - Plasmid-encoded metallo-beta-lactamase (IMP-6) conferring resistance to
      carbapenems, especially meropenem.
AB  - In 1996, Serratia marcescens KU3838 was isolated from the urine of a patient with
      a urinary tract infection at a hospital in northern Japan and was found to
      contain the plasmid pKU501. Previously, we determined that pKU501 carries
      bla(IMP) and the genes for TEM-1-type beta-lactamases as well as producing both
      types of beta-lactamases (H. Yano, A. Kuga, K. Irinoda, R. Okamoto, T. Kobayashi,
      and M. Inoue, J. Antibiot. 52:1135-1139, 1999). pKU502 is a recombinant plasmid
      that contains a 1.5-kb DNA fragment, including the metallo-beta-lactamase gene,
      and is obtained by PCR amplification of pKU501. The sequence of the metallo-beta
      lactamase gene in pKU502 was determined and revealed that this metallo-beta
      lactamase gene differed from the gene encoding IMP-1 by one point mutation,
      leading to one amino acid substitution: 640-A in the base sequence of the IMP-1
      gene was replaced by G, and Ser-196 was replaced by Gly in the mature enzyme.
      This enzyme was designated IMP-6. The strains that produced IMP-6 were resistant
      to carbapenems. The MICs of panipenem and especially meropenem were higher than
      the MIC of imipenem for these strains. The k(cat)/K(m) value of IMP-6 was about
      sevenfold higher against meropenem than against imipenem, although the MIC of
      meropenem for KU1917, which produced IMP-1, was lower than that of imipenem, and
      the MIC of panipenem was equal to that of imipenem. These results support the
      hypothesis that IMP-6 has extended substrate profiles against carbapenems.
      However, the activity of IMP-6 was very low against penicillin G and
      piperacillin. These results suggest that IMP-6 acquired high activity against
      carbapenems, especially meropenem, via the point mutation but in the process lost
      activity against penicillins. Although IMP-6 has reduced activity against
      penicillins due to this point mutation, pKU501 confers resistance to a variety of
      antimicrobial agents because it also produces TEM-1-type enzyme.

PMID- 11302794
TI  - Antileishmanial activity of an indole alkaloid from Peschiera australis.
AB  - In this study, we show the leishmanicidal effects of a chloroform fraction (CLF)
      and a purified indole alkaloid obtained from crude stem extract of Peschiera
      australis against Leishmania amazonensis, a causative agent of cutaneous
      leishmaniasis in the New World. In a bioassay-guided chemical fractionation, the
      leishmanicidal activity in CLF completely and irreversibly inhibited promastigote
      growth. This fraction was also active against amastigotes in infected murine
      macrophages. Chemical analysis of CLF identified an iboga-type indole alkaloid
      coronaridine as one of its major compounds. Coronaridine showed potent
      antileishmanial activity, inhibiting promastigote and amastigote growth.
      Promastigotes and amastigotes treated with CLF or coronaridine showed pronounced
      alterations in their mitochondria as assessed by transmission electron
      microscopy.

PMID- 11302795
TI  - Interactions of posaconazole and flucytosine against Cryptococcus neoformans.
AB  - A checkerboard methodology, based on standardized methods proposed by the
      National Committee for Clinical Laboratory Standards for broth microdilution
      antifungal susceptibility testing, was applied to study the in vitro interactions
      of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of
      Cryptococcus neoformans. Synergy, defined as a fractional inhibitory
      concentration (FIC) index of <0.50, was observed for 33% of the isolates tested.
      When synergy was not achieved, there was still a decrease in the MIC of one or
      both drugs when they were used in combination. Antagonism, defined as a FIC of
      >4.0, was not observed. The in vitro efficacy of combined therapy was confirmed
      by quantitative determination of the CFU of C. neoformans 486, an isolate against
      which the FC-SCH association yielded a synergistic interaction. To investigate
      the potential beneficial effects of this combination therapy in vivo, we
      established two experimental murine models of cryptococcosis by intracranial or
      intravenous injection of cells of C. neoformans 486. At 1 day postinfection, the
      mice were randomized into different treatment groups. One group each received
      each drug alone, and one group received the drugs in combination. While
      combination therapy was not found to be significantly more effective than each
      single drug in terms of survival, tissue burden experiments confirmed the
      potentiation of antifungal activity with the combination. Our study demonstrates
      that SCH and FC combined are significantly more active than either drug alone
      against C. neoformans in vitro as well in vivo. These findings suggest that this
      therapeutic approach could be useful in the treatment of cryptococcal infections.

PMID- 11302796
TI  - In vitro and in vivo activities of aminoadamantane and aminoalkylcyclohexane
      derivatives against Trypanosoma brucei.
AB  - We reported recently that the bloodstream form of the African trypanosome,
      Trypanosoma brucei, is sensitive to the anti-influenza virus drug rimantadine. In
      the present report we describe the trypanocidal properties of a further 62
      aminoadamantane and aminoalkylcyclohexane derivatives. Seventeen of the compounds
      were found to be more active than rimantadine, with four inhibiting growth in
      vitro of T. brucei by >90% at concentrations of 1 microM. The most active
      derivative (1-adamantyl-4-amino-cyclohexane) was about 20 to 25 times more
      effective than rimantadine. We observed a correlation between structural features
      of the derivatives and their trypanocidal properties; hydrophobic substitutions
      to the adamantane or cyclohexane rings generally enhanced activity. As with
      rimantadine, the activity in vitro varied with the pH. T. brucei was more
      sensitive in an alkaline environment (including a normal bloodstream pH of 7.4)
      and less sensitive under acidic conditions. Tests for activity in vivo were
      carried out with a mouse model of infection with a virulent strain of T. brucei.
      Although the parasitemia was not eliminated, it could be transiently suppressed
      by >98% with the most active compounds tested. These results suggest that
      aminoadamantane derivatives could have potential as a new class of trypanocidal
      agents.

PMID- 11302797
TI  - Anticandida activity is retained in P-113, a 12-amino-acid fragment of histatin
      5.
AB  - Through the analysis of a series of 25 peptides composed of various portions of
      the histatin 5 sequence, we have identified P-113, a 12-amino-acid fragment of
      histatin 5, as the smallest fragment that retains anticandidal activity
      comparable to that of the parent compound. Amidation of the P-113 C terminus
      increased the anticandidal activity of P-113 approximately twofold. The three
      histidine residues could be exchanged for three hydrophobic residues, with the
      fragment retaining anticandidal activity. However, the change of two or more of
      the five basic (lysine and arginine) residues to uncharged residues resulted in a
      substantial loss of anticandidal activity. A synthetic D-amino-acid analogue, P
      113D, was as active against Candida albicans as the L-amino-acid form. In vitro
      MIC tests in low-ionic-strength medium showed that P-113 has potent activity
      against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida
      tropicalis. These results identify P-113 as a potential antimicrobial agent in
      the treatment of oral candidiasis.

PMID- 11302798
TI  - Differences in antibiotic resistance patterns of Enterococcus faecalis and
      Enterococcus faecium strains isolated from farm and pet animals.
AB  - The prevalence of acquired resistance in 146 Enterococcus faecium and 166
      Enterococcus faecalis strains from farm and pet animals, isolated in 1998 and
      1999 in Belgium, against antibiotics used for growth promotion and for therapy
      was determined. Acquired resistance against flavomycin and monensin, two
      antibiotics used solely for growth promotion, was not detected. Avoparcin
      (glycopeptide) resistance was found sporadically in E. faecium only. Avilamycin
      resistance was almost exclusively seen in strains from farm animals. Resistance
      rates were higher in E. faecium strains from broiler chickens than in strains
      from other animal groups with tylosin and virginiamycin and in E. faecalis as
      well as in E. faecium strains with narasin and bacitracin. Resistance against
      ampicillin was mainly found among E. faecium strains from pets and was absent in
      E. faecalis. Tetracycline resistance occurred most often in strains from farm
      animals, while enrofloxacin resistance, only found in E. faecalis, occurred
      equally among strains from all origins. Resistance against gentamicin was very
      rare in broiler strains, whereas resistance rates were high in strains from other
      origins. It can be concluded that resistance against antibiotics used solely for
      growth promotion was more prevalent in E. faecium strains than in E. faecalis
      strains. With few exceptions, resistance against the different categories of
      antibiotics was more prevalent in strains from farm animals than in those from
      pets.

PMID- 11302799
TI  - Safety and pharmacokinetics of single doses of (+)-calanolide a, a novel,
      naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy,
      human immunodeficiency virus-negative human subjects.
AB  - (+)-Calanolide A is a novel, naturally occurring, nonnucleoside inhibitor of
      human immunodeficiency virus type 1 (HIV-1) reverse transcriptase first isolated
      from a tropical tree (Calophyllum lanigerum) in the Malaysian rain forest.
      Previous studies have demonstrated that (+)-calanolide A has specific activity
      against the reverse transcriptase of HIV-1 and a favorable safety profile in
      animals. In addition, (+)-calanolide A exhibits a unique HIV-1 resistance profile
      in vitro. The safety and pharmacokinetics of (+)-calanolide A was examined in
      four successive single-dose cohorts (200, 400, 600, and 800 mg) in healthy, HIV
      negative volunteers. In this initial phase I study, the toxicity of (+)
      calanolide A was minimal in the 47 subjects treated. Dizziness, taste perversion,
      headache, eructation, and nausea were the most frequently reported adverse
      events. These events were not all judged to be related to study medication nor
      were they dose related. While 51% of subjects reported mild and transient
      dizziness, in many cases this appeared to be temporally related to phlebotomy.
      Calculation of the terminal-phase half-life (t(1/2)) was precluded by
      intrasubject variability in the 200-, 400-, and 600-mg dose cohorts but was
      approximately 20 h for the 800-mg dose group. (+)-Calanolide A was rapidly
      absorbed following administration, with time to maximum concentration of drug in
      plasma (T(max)) values occurring between 2.4 and 5.2 h postdosing depending on
      the dose. Plasma levels of (+)-calanolide A at all dosing levels were quite
      variable; however, both the mean concentration in plasma (C(max)), and the area
      under the plasma concentration-time curve increased proportionately in relation
      to the dose. Although raw plasma drug levels were higher in women than in men,
      when doses were normalized for body mass, the pharmacokinetic profiles were
      virtually identical with those observed for males. In general, levels of (+)
      calanolide A in human plasma were higher than would have been predicted from
      animal studies, yet the safety profile remained benign. In conclusion, this study
      demonstrated the safety and favorable pharmacokinetic profile of single doses of
      (+)-calanolide A in healthy, HIV-negative individuals.

PMID- 11302800
TI  - Efficacy of teicoplanin-gentamicin given once a day on the basis of
      pharmacokinetics in humans for treatment of enterococcal experimental
      endocarditis.
AB  - With the aim of investigating home therapy for enterococcal endocarditis, we
      compared the efficacy of teicoplanin combined with gentamicin given once a day or
      in three daily doses (t.i.d.) with the standard treatment, ampicillin plus
      gentamicin administered t.i.d., for treating experimental enterococcal
      endocarditis. The antibiotics were administered by using "human-like
      pharmacokinetics" (H-L), i.e, pharmacokinetics like those in humans, that
      simulated the profiles of these drugs in human serum. Animals with catheter
      induced endocarditis were infected intravenously with 10(8) CFU of Enterococcus
      faecalis EF91 (MICs and MBCs of ampicillin, gentamicin, and teicoplanin, 0.5 and
      32, 16 and 32, and 0.5 and 1 microg/ml, respectively) and were treated for 3 days
      with ampicillin H-L at 2 g every 4 h plus gentamicin H-L at 1 mg/kg every 8 h, or
      teicoplanin H-L at 10 mg/kg every 24 h, alone or combined with gentamicin,
      administered at dose of H-L at 1 mg/kg every 8 h or H-L at 4.5 mg/kg every 24 h.
      The results of therapy for experimental endocarditis due to EF91 showed that
      teicoplanin alone was as effective as ampicillin alone in reducing the bacterial
      load (P > 0.05). The combination of ampicillin or teicoplanin with gentamicin was
      more effective than the administration of both drugs alone in reducing the
      log(10)CFU/gram of aortic vegetation (P < 0.01 and P < 0.05, respectively).
      Teicoplanin plus gentamicin H-L at 4.5 mg/kg, both administered every 24 h,
      showed an efficacy equal to the "gold standard," ampicillin plus gentamicin H-L
      at 1 mg/kg t.i.d. (P > 0.05). Increasing the interval of administration of
      gentamicin to a single daily dose combined with teicoplanin resulted in a
      reduction of bacteria in the vegetations equivalent to that achieved with the
      recommended regimen of ampicillin plus thrice-daily gentamicin in the treatment
      of experimental endocarditis due to E. faecalis. Teicoplanin plus gentamicin,
      both administered once a day, may be useful home therapy for selected cases of
      enterococcal endocarditis.

PMID- 11302801
TI  - In vivo efficacy of trovafloxacin against Bacteroides fragilis in mixed infection
      with either Escherichia coli or a vancomycin-resistant strain of Enterococcus
      faecium in an established-abscess murine model.
AB  - The pharmacodynamic and pharmacokinetic properties of trovafloxacin were studied
      in a standardized murine model of established subcutaneous abscesses. Daily
      dosing regimens of 37.5 to 300 mg/kg every 8 h (q8h) or every 24 h (q24h) were
      started 3 days after inoculation with mixtures containing either Bacteroides
      fragilis-Escherichia coli-autoclaved cecal contents (ACC) or B. fragilis
      vancomycin-resistant Enterococcus faecium (VREF)-ACC. Treatment was continued for
      3 or 5 days. The efficacy of treatment was determined by the decrease in abscess
      bacterial counts and abscess weights, as well as by the reduction in inflammation
      (biodistribution of (99m)Tc-HYNIC immunoglobulin G) compared to saline-treated
      controls. Trovafloxacin showed a significant dose-response effect on the
      bacterial counts, weight, and inflammation of B. fragilis-E. coli abscesses after
      3 and/or 5 days of treatment. A maximum 3.4 and 3.1 log(10) reduction in
      CFU/abscess in the respective B. fragilis and E. coli bacterial counts was
      attained after 5 days of treatment with daily doses of 300 mg/kg. The peak serum
      concentration was more predictive for effect than the area under the
      concentration-time curve. The C(max) was the pharmacodynamic index most
      predictive for success, and the efficacy of the q24h regimens was significantly
      better than the q8h regimens. The antibiotic was ineffective against the VREF in
      mixed infection with B. fragilis, while the killing of the anaerobe in the same
      combination was significantly less than in the E. coli combination (P < 0.05). We
      conclude that this is a useful model for studying the activity of antimicrobials
      for the treatment of small (<1-cm), undrainable, mixed-infection abscesses. In
      addition, we have shown for the first time that a decrease in bacterial numbers
      also leads to a reduction in both abscess weight and inflammation.

PMID- 11302802
TI  - Multidrug-resistant urinary tract isolates of Escherichia coli: prevalence and
      patient demographics in the United States in 2000.
AB  - Concurrent resistance to antimicrobials of different structural classes has
      arisen in a multitude of bacterial species and may complicate the therapeutic
      management of infections, including those of the urinary tract. To assess the
      current breadth of multidrug resistance among urinary isolates of Escherichia
      coli, the most prevalent pathogen contributing to these infections, all pertinent
      results in The Surveillance Network Database-USA from 1 January to 30 September
      2000 were analyzed. Results were available for 38,835 urinary isolates of E. coli
      that had been tested against ampicillin, cephalothin, ciprofloxacin,
      nitrofurantoin, and trimethoprim-sulfamethoxazole. Of these isolates, 7.1% (2,763
      of 38,835) were resistant to three or more agents and considered multidrug
      resistant. Among the multidrug-resistant isolates, 97.8% were resistant to
      ampicillin, 92.8% were resistant to trimethoprim-sulfamethoxazole, 86.6% were
      resistant to cephalothin, 38.8% were resistant to ciprofloxacin, and 7.7% were
      resistant to nitrofurantoin. The predominant phenotype among multidrug-resistant
      isolates (57.9%; 1,600 of 2,793) included resistance to ampicillin, cephalothin,
      and trimethoprim-sulfamethoxazole. This was the most common phenotype regardless
      of patient age, gender, or inpatient-outpatient status and in eight of the nine
      U.S. Bureau of the Census regions. Rates of multidrug resistance were
      demonstrated to be higher among males (10.4%) than females (6.6%), among patients
      > 65 years of age (8.7%) than patients < or = 17 (6.8%) and 18 to 65 (6.1%) years
      of age, and among inpatients (7.6%) than outpatients (6.9%). Regionally, the
      rates ranged from 4.3% in the West North Central region to 9.2% in the West South
      Central region. Given the current prevalence of multidrug resistance among
      urinary tract isolates of E. coli in the United States (7.1%), continued local,
      regional, and national surveillance is warranted.

PMID- 11302803
TI  - Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP
      rhamnose synthetic enzymes and development of a microtiter plate-based screen for
      inhibitors of conversion of dTDP-glucose to dTDP-rhamnose.
AB  - An L-rhamnosyl residue plays an essential structural role in the cell wall of
      Mycobacterium tuberculosis. Therefore, the four enzymes (RmlA to RmlD) that form
      dTDP-rhamnose from dTTP and glucose-1-phosphate are important targets for the
      development of new tuberculosis therapeutics. M. tuberculosis genes encoding
      RmlA, RmlC, and RmlD have been identified and expressed in Escherichia coli. It
      is shown here that genes for only one isotype each of RmlA to RmlD are present in
      the M. tuberculosis genome. The gene for RmlB is Rv3464. Rv3264c was shown to
      encode ManB, not a second isotype of RmlA. Using recombinant RmlB, -C, and -D
      enzymes, a microtiter plate assay was developed to screen for inhibitors of the
      formation of dTDP-rhamnose. The three enzymes were incubated with dTDP-glucose
      and NADPH to form dTDP-rhamnose and NADP(+) with a concomitant decrease in
      optical density at 340 nm (OD(340)). Inhibitor candidates were monitored for
      their ability to lower the rate of OD(340) change. To test the robustness and
      practicality of the assay, a chemical library of 8,000 compounds was screened.
      Eleven inhibitors active at 10 microM were identified; four of these showed
      activities against whole M. tuberculosis cells, with MICs from 128 to 16
      microg/ml. A rhodanine structural motif was present in three of the enzyme
      inhibitors, and two of these showed activity against whole M. tuberculosis cells.
      The enzyme assay was used to screen 60 Peruvian plant extracts known to inhibit
      the growth of M. tuberculosis in culture; two extracts were active inhibitors in
      the enzyme assay at concentrations of less than 2 microg/ml.

PMID- 11302804
TI  - Activities of bismuth thiols against staphylococci and staphylococcal biofilms.
AB  - Indwelling medical devices are associated with infectious complications.
      Incorporating antimicrobials into indwelling materials may reduce bacterial
      colonization. Bismuth thiols are antibiofilm agents with up to 1,000-fold-greater
      antibacterial activity than other bismuth salts. Staphylococci are particularly
      sensitive, as determined by agar diffusion and broth dilution susceptibility
      testing. Bismuth-ethanedithiol inhibited 10 methicillin-resistant Staphylococcus
      epidermidis strains at 0.9 to 1.8, Staphylococcus aureus ATCC 25923 at 2.4, and
      S. epidermidis ATCC 12228 at 0.1 microM Bi(3+). Antiseptic-resistant S. aureus
      was sensitive to bismuth-2-3-dimercaptopropanol (BisBAL) at < or = 7 microM
      Bi(3+). Hydrogel-coated polyurethane rods soaked in BisBAL inhibited S.
      epidermidis for 39 days (inhibitory zone diameter in agar, > or = 30 mm for > 25
      days). Slime from 16 slime-producing S. epidermidis strains was inhibited
      significantly by bismuth-3,4-dimercaptotoluene (BisTOL), but not by AgNO3, at
      subinhibitory concentrations. In conclusion, bismuth-thiols are bacteriostatic
      and bactericidal against staphylococci, including resistant organisms, but are
      also inhibitors of slime at subinhibitory concentrations. At subinhibitory
      concentrations, BisTOL may be useful in preventing the colonization and infection
      of indwelling intravascular lines, since staphylococci are important pathogens in
      this setting.

PMID- 11302805
TI  - In vitro activities of RWJ-54428 (MC-02,479) against multiresistant gram-positive
      bacteria.
AB  - RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity
      against gram-positive bacteria. In a broth microdilution susceptibility test
      against methicillin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as
      active as vancomycin, with an MIC at which 90% of isolates are inhibited
      (MIC(90)) of 2 microg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32
      times more active than imipenem, with an MIC(90) of 2 microg/ml. RWJ-54428 was
      active against S. aureus, Staphylococcus epidermidis, and Staphylococcus
      haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC
      range, < or = 0.0625 to 1 microg/ml). RWJ-54428 was eight times more potent than
      methicillin and cefotaxime against methicillin-susceptible S. aureus (MIC(90),
      0.5 microg/ml). For ampicillin-susceptible Enterococcus faecalis (including
      vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428
      had an MIC(90) of 0.125 microg/ml. RWJ-54428 was also active against Enterococcus
      faecium, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains.
      The potency against enterococci correlated with ampicillin susceptibility; RWJ
      54428 MICs ranged between < or = 0.0625 and 1 microg/ml for ampicillin
      susceptible strains and 0.125 and 8 microg/ml for ampicillin-resistant strains.
      RWJ-54428 was more active than penicillin G and cefotaxime against penicillin
      resistant, -intermediate, and -susceptible strains of Streptococcus pneumoniae
      (MIC(90)s, 0.25, 0.125, and < or = 0.0625 microg/ml, respectively). RWJ-54428 was
      only marginally active against most gram-negative bacteria; however, significant
      activity was observed against Haemophilus influenzae and Moraxella catarrhalis
      (MIC(90)s, 0.25 and 0.5 microg/ml, respectively). This survey of the
      susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to
      RWJ-54428 indicates that this new cephalosporin has the potential to be useful in
      the treatment of infections due to gram-positive bacteria, including strains
      resistant to currently available antimicrobials.

PMID- 11302806
TI  - Mechanism and suppression of lysostaphin resistance in oxacillin-resistant
      Staphylococcus aureus.
AB  - The potential for the development of resistance in oxacillin-resistant
      Staphylococcus aureus (ORSA) to lysostaphin, a glycylglycine endopeptidase
      produced by Staphylococcus simulans biovar staphylolyticus, was examined in vitro
      and in an in vivo model of infection. Following in vitro exposure of ORSA to
      subinhibitory concentrations of lysostaphin, lysostaphin-resistant mutants were
      idenitifed among all isolates examined. Resistance to lysostaphin was associated
      with a loss of resistance to beta-lactams and a change in the muropeptide
      interpeptide cross bridge from pentaglycine to a single glycine. Mutations in
      femA, the gene required for incorporation of the second and third glycines into
      the cross bridge, were found following PCR amplification and nucleotide sequence
      analysis. Complementation of lysostaphin-resistant mutants with pBBB31, which
      encodes femA, restored the phenotype of oxacillin resistance and lysostaphin
      susceptibility. Addition of beta-lactam antibiotics to lysostaphin in vitro
      prevented the development of lysostaphin-resistant mutants. In the rabbit model
      of experimental endocarditis, administration of a low dose of lysostaphin for 3
      days led predictably to the appearance of lysostaphin-resistant ORSA mutants in
      vegetations. Coadministration of nafcillin with lysostaphin prevented the
      emergence of lysostaphin-resistant mutants and led to a mean reduction in aortic
      valve vegetation counts of 7.5 log(10) CFU/g compared to those for untreated
      controls and eliminated the isolation of lysostaphin-resistant mutants from
      aortic valve vegetations. Treatment with nafcillin and lysostaphin given alone
      led to mean reductions of 1.35 and 1.65 log(10) CFU/g respectively. In ORSA,
      resistance to lysostaphin was associated with mutations in femA, but resistance
      could be suppressed by the coadministration of beta-lactam antibiotics.

PMID- 11302807
TI  - Short-term measures of relative efficacy predict longer-term reductions in human
      immunodeficiency virus type 1 RNA levels following nelfinavir monotherapy.
AB  - We calculated the relative efficacy of treatment, defined as the rate of decline
      of virus levels in plasma during treatment relative to the rate of decline during
      highly potent combination therapy, in human immunodeficiency virus type 1 (HIV-1)
      patients treated for 56 days with different doses of the protease inhibitor
      nelfinavir. Relative efficacies based on the rate of decline of HIV-1 RNA levels
      in plasma over the first 14 to 21 days correlated with drug dose and viral load
      reduction by day 56. Calculation of relative treatment efficacies over the first
      2 to 3 weeks of treatment can allow rapid assessment of new antiretroviral agents
      and dosing regimens, reducing the need to keep subjects in clinical trials on
      monotherapy for prolonged periods of time. Relative efficacy may also serve as a
      measure of treatment efficacy in patients in initiating established therapies.

PMID- 11302808
TI  - Ganciclovir and cidofovir treatment of cytomegalovirus-induced myocarditis in
      mice.
AB  - The cardiovascular disease myocarditis is characterized by inflammation and
      necrosis of cardiac muscle. This disease has been associated with various viral
      etiologies, including cytomegalovirus (CMV). Murine CMV (MCMV) infection of adult
      BALB/c mice produces a disease with acute and chronic phases similar to that
      found in humans. In our murine model, we have investigated the therapeutic
      efficacy of antiviral drug administration on myocarditis. Two drugs commonly used
      for CMV treatment, ganciclovir and cidofovir, were subjected to trials, with both
      drugs showing potent antiviral activity against MCMV both in vitro and in vivo.
      The acute phase of myocarditis was significantly reduced when antiviral therapy
      commenced 24 h postinfection. Such treatment also reduced the severity of the
      chronic phase of myocarditis. In contrast, antiviral treatment commencing after
      the acute phase had no effect on chronic myocarditis. Reinfection of mice with
      MCMV caused exacerbation of myocardial inflammation. Such an increase in severity
      of myocarditis could be prevented with either ganciclovir or cidofovir treatment,
      but the preexisting inflammation and necrosis of the myocardium persisted. These
      data highlight possible therapeutic uses of antiviral drugs in viral myocarditis
      as well as further elucidating the pathogenic nature of the disease.

PMID- 11302809
TI  - Inhibition of intramacrophage growth of Penicillium marneffei by 4
      aminoquinolines.
AB  - The antimicrobial activities of chloroquine (CQ) and several 4-aminoquinoline
      drugs were tested against Penicillium marneffei, an opportunistic fungus that
      invades and grows inside macrophages and causes disseminated infection in AIDS
      patients. Human THP1 and mouse J774 macrophages were infected in vitro with P.
      marneffei conidia and treated with different doses of drugs for 24 to 48 h
      followed by cell lysis and the counting of P. marneffei CFU. CQ and amodiaquine
      exerted a dose-dependent inhibition of fungal growth, whereas quinine and
      artemisinin were fungistatic and not fungicidal. The antifungal activity of CQ
      was not due to an impairment of fungal iron acquisition in that it was not
      reversed by the addition of iron nitrilotriacetate, FeCl3, or iron ammonium
      citrate. Perl's staining indicated that CQ did not alter the ability of J774
      cells to acquire iron from the medium. Most likely, CQ's antifungal activity is
      due to an increase in the intravacuolar pH and a disruption of pH-dependent
      metabolic processes. Indeed, we demonstrate that (i) bafilomycin A1 and ammonium
      chloride, two agents known to alkalinize intracellular vesicles by different
      mechanisms, were inhibitory as well and (ii) a newly synthesized 4-amino-7
      chloroquinoline molecule (compound 9), lacking the terminal amino side chain of
      CQ that assists in drug accumulation, did not inhibit P. marneffei growth. These
      results suggest that CQ has a potential for use in prophylaxis of P. marneffei
      infections in human immunodeficiency virus-infected patients in countries where
      P. marneffei is endemic.

PMID- 11302810
TI  - Susceptibility testing of Aspergillus flavus: inoculum dependence with
      itraconazole and lack of correlation between susceptibility to amphotericin B in
      vitro and outcome in vivo.
AB  - We have attempted to validate in Aspergillus flavus the main in vitro
      methodologies that have been used to detect resistance in Aspergillus fumigatus.
      We developed a murine model with two A. flavus isolates, one that was apparently
      resistant in vitro to amphotericin B (AFL5) and another that was resistant to
      itraconazole (AFL8). No correlation was found for amphotericin B in AFL5, since
      the in vivo response was compatible with a susceptible isolate. Modification of
      the in vitro susceptibility test methodology for amphotericin B was unsuccessful.
      Although AFL8 was apparently resistant to itraconazole in vitro, it was found to
      be susceptible in vivo. Additional in vitro work has detected weaknesses in the
      in vitro susceptibility methodology validated for A. fumigatus when applied to A.
      flavus. The principal problems are that changes in the inoculum have a large
      effect on the MICs of itraconazole for some A. flavus strains and that a trailing
      end point and spore sediment often appear when an inoculum with a higher colony
      count is used. We propose a modified method using a final inoculum of 2.5 x 10(4)
      CFU per ml of RPMI 1640 medium with 2% glucose buffered to pH 7.0 in a microtiter
      format, incubated for 48 h with no growth end point. Validation of this
      methodology requires one or more itraconazole-resistant A. flavus isolates, which
      have yet to be identified.

PMID- 11302811
TI  - Activities of BMS 284756 (T-3811) against Haemophilus influenzae, Moraxella
      catarrhalis, and Streptococcus pneumoniae isolates from SENTRY antimicrobial
      surveillance program medical centers in Latin America (1999).
AB  - The antimicrobial activity of BMS 284756, a novel des-F(6)-quinolone, was
      comparatively evaluated against 257 Streptococcus pneumoniae, 198 Haemophilus
      influenzae, and 88 Moraxella catarrhalis strains isolated in Latin America
      between July and September of 1999 as part of the SENTRY Antimicrobial
      Surveillance Program. Nearly 28.0% of S. pneumoniae strains were nonsusceptible
      to penicillin. The rank order of quinolone potency versus S. pneumoniae was BMS
      284756 (MIC at which 90% of isolates were inhibited [MIC(90)], 0.12 microg/ml) >
      trovafloxacin (MIC(90), 0.25 microg/ml) > gatifloxacin (MIC(90), 0.5 microg/ml) >
      levofloxacin and ciprofloxacin (MIC(90), 1 to 2 microg/ml). All S. pneumoniae
      strains that were not susceptible to other quinolones were inhibited by BMS
      284756 at < or = 2 microg/ml. The overall prevalence of beta-lactamase production
      was 15.2% in H. influenzae and 98.9% in M. catarrhalis. BMS 284756 showed
      excellent potency and spectrum against this group of pathogens, inhibiting all
      isolates at < or = 0.12 microg/ml. BMS 284756 exhibited activity similar to those
      displayed by the new fluoroquinolones, such as levofloxacin, trovafloxacin, or
      gatifloxacin, and could be a therapeutic option for empirical treatment of
      community-acquired respiratory tract infections.

PMID- 11302812
TI  - Enhanced expression of the multidrug efflux pumps AcrAB and AcrEF associated with
      insertion element transposition in Escherichia coli mutants Selected with a
      fluoroquinolone.
AB  - The development of fluoroquinolone resistance in Escherichia coli may be
      associated with mutations in regulatory gene loci such as marRAB that lead to
      increased multidrug efflux, presumably through activation of expression of the
      AcrAB multidrug efflux pump. We found that multidrug-resistant (MDR) phenotypes
      with enhanced efflux can also be selected by fluoroquinolones from marRAB- or
      acrAB-inactivated E. coli K-12 strains having a single mutation in the quinolone
      resistance-determining region of gyrA. Mutant 3-AG100MKX, obtained from a mar
      knockout strain after two selection steps, showed enhanced expression of acrB in
      a reverse transcriptase PCR associated with insertion of IS186 into the AcrAB
      repressor gene acrR. In vitro selection experiments with acrAB knockout strains
      yielded MDR mutants after a single step. Enhanced efflux in these mutants was due
      to increased expression of acrEF and associated with insertion of IS2 into the
      upstream region of acrEF, presumably creating a hybrid promoter. These
      observations confirm the importance of efflux-associated nontarget gene mutations
      and indicate that transposition of genetic elements may have a role in the
      development of fluoroquinolone resistance in E. coli.

PMID- 11302813
TI  - Activities and conformational fitting of 1,4-naphthoquinone derivatives and other
      cyclic 1,4-diones tested in vitro against Pneumocystis carinii.
AB  - Atovaquone is a chemotherapeutic agent used to treat pneumonia caused by
      Pneumocystis carinii in some immunocompromised patients. A set of cyclic 1,4
      diones were tested in vitro for ability to inhibit growth of P. carinii,
      including 22 variously substituted 1,4-naphthoquinones, one bis-1,4
      naphthoquinone, and three other quinones. For comparison, the antipneumocystic
      primaquine and its 5-hydroxy-6-desmethyl metabolite were also tested. At 1.0
      microg/ml, seven compounds inhibited growth by at least 39%, with atovaquone at
      92%; of these seven, five are 2-hydroxy-1,4-naphthoquinones, while one is a 2
      chloro- and another is a 2-methyl-1,4-naphthoquinone. At 0.1 microg/ml, however,
      the most active compound tested was the primaquine metabolite, which inhibited
      growth by more than 42% at this concentration. To ascertain a structure-activity
      relationship, all 1,4-naphthoquinones were compared conformationally by means of
      computer-based molecular modeling (Spartan) incorporating the Sybyl force field.
      Without exception, for all 21 monomers tested, the substituent at position 3 of
      the 1,4-naphthoquinone favored activity most strongly when it simultaneously
      occupied (i) space centered at about 3 A from position 3, without projecting
      steric bulk from the area encompassed by atovaquone's cyclohexyl ring, and (ii)
      roughly planar space at about 7.3 A from position 3, without projecting steric
      bulk perpendicularly. This structure-activity relationship may prove useful in
      the rational design of better antipneumocystis agents.

PMID- 11302814
TI  - Penicillin-binding protein 5 and expression of ampicillin resistance in
      Enterococcus faecium.
AB  - We report a structural and transcriptional analysis of the pbp5 region of
      Enterococcus faecium C68. pbp5 exists within a larger operon that includes
      upstream open reading frames (ORFs) corresponding to previously reported psr
      (penicillin-binding protein synthesis repressor) and ftsW (whose product is a
      transmembrane protein that interacts with PBP3 in Escherichia coli septum
      formation) genes. Hybridization of mRNA from C68, CV133, and four ampicillin
      resistant CV133 mutants revealed four distinct transcripts from this region,
      consisting of (i) E. faecium ftsW (ftsW(Efm)) alone; (ii) psr and pbp5; (iii)
      pbp5 alone; and (iv) ftsW(Efm), psr, and pbp5. Quantities of the different
      transcripts varied between strains and did not always correlate with quantities
      of PBP5 or levels of ampicillin resistance. Since the psr of C68 is presumably
      nonfunctional due to an insertion of an extra nucleotide in the codon for the
      44th amino acid, the region extending from the ftsW(Efm) promoter through the
      pbp5 gene of C68 was cloned in E. coli to facilitate mutagenesis. The psr ORF was
      regenerated using site-directed mutagenesis and introduced into E. faecium D344
      SRF on conjugative shuttle vector pTCV-lac (pCWR558 [psr ORF interrupted];
      pCWR583 [psr ORF intact]). Ampicillin MICs for both D344-SRF(pCWR558) and D344
      SRF(pCWR583) were 64 microg/ml. Quantities of pbp5 transcript and protein were
      similar in strains containing either construct regardless of whether they were
      grown in the presence or absence of ampicillin, arguing against a role for PSR as
      a repressor of pbp5 transcription. However, quantities of psr transcript were
      increased in D344-SRF(pCWR583) compared to D344-SRF(pCWR558), especially after
      growth in ampicillin; suggesting that PSR acts in some manner to activate its own
      transcription.

PMID- 11302815
TI  - Improved efficacy of ciprofloxacin administered in polyethylene glycol-coated
      liposomes for treatment of Klebsiella pneumoniae pneumonia in rats.
AB  - Animal and clinical data show that high ratios of the area under the
      concentration-time curve and the peak concentration in blood to the MIC of
      fluoroquinolones for a given pathogen are associated with a favorable outcome.
      The present study investigated whether improvement of the therapeutic potential
      of ciprofloxacin could be achieved by encapsulation in polyethylene glycol (PEG)
      coated long-circulating sustained-release liposomes. In a rat model of unilateral
      Klebsiella pneumoniae pneumonia (MIC = 0.1 microg/ml), antibiotic was
      administered at 12- or 24-h intervals at twofold-increasing doses. A treatment
      period of 3 days was started 24 h after inoculation of the left lung, when the
      bacterial count had increased 1,000-fold and some rats had positive blood
      cultures. The infection was fatal within 5 days in untreated rats. Administration
      of ciprofloxacin in the liposomal form resulted in delayed ciprofloxacin
      clearance and increased and prolonged ciprofloxacin concentrations in blood and
      tissues. The ED(50) (dosage that results in 50% survival) of liposomal
      ciprofloxacin was 3.3 mg/kg of body weight/day given once daily, and that of free
      ciprofloxacin was 18.9 mg/kg/day once daily or 5.1 mg/kg/day twice daily. The
      ED(90) of liposomal ciprofloxacin was 15.0 mg/kg/day once daily compared with
      36.0 mg/kg/day twice daily for free ciprofloxacin; 90% survival could not be
      achieved with free ciprofloxacin given once daily. In summary, the therapeutic
      efficacy of liposomal ciprofloxacin was superior to that of ciprofloxacin in the
      free form. PEG-coated liposomal ciprofloxacin was well tolerated in relatively
      high doses, permitting once daily administration with relatively low
      ciprofloxacin clearance and without compromising therapeutic efficacy.

PMID- 11302816
TI  - In vitro antifungal activity of KP-103, a novel triazole derivative, and its
      therapeutic efficacy against experimental plantar tinea pedis and cutaneous
      candidiasis in guinea pigs.
AB  - The in vitro activity of KP-103, a novel triazole derivative, against pathogenic
      fungi that cause dermatomycoses and its therapeutic efficacy against plantar
      tinea pedis and cutaneous candidiasis in guinea pigs were investigated. MICs were
      determined by a broth microdilution method with morpholinepropanesulfonic acid
      buffered RPMI 1640 medium for Candida species and with Sabouraud dextrose broth
      for dermatophytes and by an agar dilution method with medium C for Malassezia
      furfur. KP-103 was the most active of all the drugs tested against Candida
      albicans (geometric mean [GM] MIC, 0.002 microg/ml), other Candida species
      including Candida parapsilosis and Candida glabrata (GM MICs, 0.0039 to 0.0442
      microg/ml), and M. furfur (GM MIC, 0.025 microg/ml). KP-103 (1% solution) was
      highly effective as a treatment for guinea pigs with cutaneous candidiasis and
      achieved mycological eradication in 8 of the 10 infected animals, whereas none of
      the imidazoles tested (1% solutions) was effective in even reducing the levels of
      the infecting fungi. KP-103 was as active as clotrimazole and neticonazole but
      was less active than lanoconazole and butenafine against Trichophyton rubrum (MIC
      at which 80% of isolates are inhibited [MIC(80)], 0.125 microg/ml) and
      Trichophyton mentagrophytes (MIC(80), 0.25 microg/ml). However, KP-103 (1%
      solution) exerted therapeutic efficacy superior to that of neticonazole and
      comparable to those of lanoconazole and butenafine, yielding negative cultures
      for all samples from guinea pigs with plantar tinea pedis tested. This suggests
      that KP-103 has better pharmacokinetic properties in skin tissue than the
      reference drugs. Because the in vitro activity of KP-103, unlike those of the
      reference drugs, against T. mentagrophytes was not affected by hair as a
      keratinic substance, its excellent therapeutic efficacy seems to be attributable
      to good retention of its antifungal activity in skin tissue, in addition to its
      potency.

PMID- 11302817
TI  - Accurate prediction of macrolide resistance in Helicobacter pylori by a PCR line
      probe assay for detection of mutations in the 23S rRNA gene: multicenter
      validation study.
AB  - Helicobacter pylori strains from 299 patients were tested in six laboratories in
      different countries. Macrolide susceptibility of the strains was determined by
      agar dilution (17.4%) or the epsilometer test (82.6%). Mutations in the 23S
      ribosomal DNA (rDNA) that are associated with macrolide resistance were analyzed
      by PCR and reverse hybridization (PCR-line probe assay [LiPA]). This method
      identifies A2115G, G2141A, A2142G, A2142C, A2142T, A2143G, and A2143C mutations
      in the 23S rDNA. vacA s-region (s1a, s1b, s1c, and s2) and m-region (m1, m2a, and
      m2b) genotypes and cagA status were also determined using another PCR-LiPA
      system. Of the 299 strains investigated by MIC testing, 130 (43.5%) were
      resistant and 169 (56.5%) were susceptible to clarithromycin. Of the 130
      resistant strains, 127 (97.7%) contained 23S rDNA mutations, whereas 167 (98.8%)
      of the 169 susceptible strains contained wild-type sequences. The predominant
      mutations were A2143G (45.2%) and A2142G (33.3%). Twenty-eight (19.8%) strains
      contained multiple 23S rDNA mutations. Only five resistant strains contained the
      A2142C mutation (three of these in combination with the A2142G mutation), and the
      A2115G, G2141A, A2142T, and A2143C mutations were not found. MICs of
      clarithromycin for the A2142G mutant strains were significantly higher than MICs
      for the A2143G strains. Although there was no significant association between 23S
      rDNA mutations and the vacA and cagA status, clarithromycin-susceptible strains
      more often contained mixed vacA genotypes, indicating the presence of multiple H.
      pylori strains. In conclusion, our data confirmed the very strong association
      between 23S rDNA mutations and macrolide resistance and showed that the PCR-LiPA
      permits accurate and reliable diagnosis of macrolide resistance in H. pylori.

PMID- 11302818
TI  - Effects of miltefosine and other alkylphosphocholines on human intestinal
      parasite Entamoeba histolytica.
AB  - The protozoan parasite Entamoeba histolytica is the cause of amoebic dysentery
      and liver abscess. It is therefore responsible for significant morbidity and
      mortality in a number of countries. Infections with E. histolytica are treated
      with nitroimidazoles, primarily with metronidazole. At this time, there is a lack
      of useful alternative classes of substances for the treatment of invasive
      amoebiasis. Alkylphosphocholines (alkyl-PCs) such as hexadecyl-PC (miltefosine)
      were originally developed as antitumor agents, but recently they have been
      successfully used for the treatment of visceral leishmaniasis in humans. We
      examined hexadecyl-PC and several other alkyl-PCs with longer alkyl chains, with
      and without double bond(s), for their activity against two strains of E.
      histolytica. The compounds with the highest activity were oleyl-PC, octadecyl-PC,
      and nonadecenyl-PC, with 50% effective concentrations for 48 h of treatment
      between 15 and 21 microM for strain SFL-3 and between 73 and 98 microM for strain
      HM-1:IMSS. We also tested liposomal formulations of these alkyl-PCs and
      miltefosine. The alkyl-PC liposomes showed slightly lower activity, but are
      expected to be well tolerated. Liposomal formulations of oleyl-PC or closely
      related alkyl-PCs could be promising candidates for testing as broad-spectrum
      antiprotozoal and antitumor agents in humans.

PMID- 11302819
TI  - Antibiotic susceptibilities of genetically characterized Streptococcus milleri
      group strains.
AB  - Previous studies of the antibiotic susceptibility of Streptococcus milleri group
      organisms have distinguished among species by using phenotypic techniques. Using
      44 isolates that were speciated by 16S rRNA gene sequencing, we studied the MICs
      and minimum bactericidal concentrations of penicillin, ampicillin, ceftriaxone,
      and clindamycin for Streptococcus intermedius, Streptococcus constellatus, and
      Streptococcus anginosus. None of the organisms was resistant to beta-lactam
      antibiotics, although a few isolates were intermediately resistant; one strain of
      S. anginosus was tolerant to ampicillin, and another was tolerant to ceftriaxone.
      Six isolates were resistant to clindamycin, with representation from each of the
      three species. Relatively small differences in antibiotic susceptibilities among
      species of the S. milleri group show that speciation is unlikely to be important
      in selecting an antibiotic to treat infection caused by one of these isolates.

PMID- 11302820
TI  - Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia
      coli strains from China: role of acrR mutations.
AB  - The genetic basis for fluoroquinolone resistance was examined in 30 high-level
      fluoroquinolone-resistant Escherichia coli clinical isolates from Beijing, China.
      Each strain also demonstrated resistance to a variety of other antibiotics. PCR
      sequence analysis of the quinolone resistance-determining region of the
      topoisomerase genes (gyrA/B, parC) revealed three to five mutations known to be
      associated with fluoroquinolone resistance. Western blot analysis failed to
      demonstrate overexpression of MarA, and Northern blot analysis did not detect
      overexpression of soxS RNA in any of the clinical strains. The AcrA protein of
      the AcrAB multidrug efflux pump was overexpressed in 19 of 30 strains of E. coli
      tested, and all 19 strains were tolerant to organic solvents. PCR amplification
      of the complete acrR (regulator/repressor) gene of eight isolates revealed amino
      acid changes in four isolates, a 9-bp deletion in another, and a 22-bp
      duplication in a sixth strain. Complementation with a plasmid-borne wild-type
      acrR gene reduced the level of AcrA in the mutants and partially restored
      antibiotic susceptibility 1.5- to 6-fold. This study shows that mutations in acrR
      are an additional genetic basis for fluoroquinolone resistance.

PMID- 11302821
TI  - Inhibitory activities of lansoprazole against respiration in Helicobacter pylori.
AB  - Lansoprazole and its derivative AG-1789 dose-dependently inhibited cellular
      respiration by an endogenous substrate and decreased the ATP level in
      Helicobacter pylori cells. The inhibitory action of lansoprazole and AG-1789
      against respiration was specific to substrates such as pyruvate and alpha
      ketoglutarate and similar to the inhibitory action of rotenone, which is an
      inhibitor for the mitochondrial respiratory chain. Growth inhibition by
      lansoprazole and AG-1789 as well as by rotenone was augmented at high oxygen
      concentrations under atmospheric conditions. Since the 50% inhibitory
      concentrations of these compounds for the respiration were close to their MICs
      for H. pylori growth, the growth inhibition might be due to respiratory
      inhibition by these compounds.

PMID- 11302822
TI  - Resistance and adaptation to quinidine in Saccharomyces cerevisiae: role of QDR1
      (YIL120w), encoding a plasma membrane transporter of the major facilitator
      superfamily required for multidrug resistance.
AB  - As predicted based on structural considerations, we show results indicating that
      the member of the major facilitator superfamily encoded by Saccharomyces
      cerevisiae open reading frame YIL120w is a multidrug resistance determinant.
      Yil120wp was implicated in yeast resistance to ketoconazole and quinidine, but
      not to the stereoisomer quinine; the gene was thus named QDR1. Qdr1p was proved
      to alleviate the deleterious effects of quinidine, revealed by the loss of cell
      viability following sudden exposure of the unadapted yeast population to the
      drug, and to allow the earlier eventual resumption of exponential growth under
      quinidine stress. However, QDR1 gene expression had no detectable effect on the
      susceptibility of yeast cells previously adapted to quinidine. Fluorescence
      microscopy observation of the distribution of the Qdr1-green fluorescent protein
      fusion protein in living yeast cells indicated that Qdr1p is a plasma membrane
      protein. We also show experimental evidence indicating that yeast adaptation to
      growth with quinidine involves the induction of active expulsion of the drug from
      preloaded cells, despite the fact that this antiarrhythmic and antimalarial
      quinoline ring-containing drug is not present in the yeast natural environment.
      However, we were not able to prove that Qdr1p is directly implicated in this
      export. Results clearly suggest that there are other unidentified quinidine
      resistance mechanisms that can be used in the absence of QDR1.

PMID- 11302823
TI  - Prolonged antimicrobial activity of a catheter containing chlorhexidine-silver
      sulfadiazine extends protection against catheter infections in vivo.
AB  - The present study evaluated in vitro and in vivo a new chlorhexidine (C)-silver
      sulfadiazine (S) vascular catheter (the CS2 catheter) characterized by a higher C
      content and by the extended release of the surface-bound antimicrobials. The CS2
      catheter was compared with a first-generation, commercially available CS catheter
      (the CS1 catheter). The CS2 catheter produced slightly smaller zones of
      inhibition (mean difference, 0.9 mm [P < 0.001]) at 24 h against Staphylococcus
      aureus and five other microorganisms by several different methodologies. However,
      in a rabbit model, both CS catheters were similarly efficacious in preventing a
      catheter infection when the rabbits were inoculated with 10(4) to 10(7) CFU of S.
      aureus at the time of catheter insertion. The CS2 catheter retained its
      antimicrobial activity significantly longer in vitro and in vivo (half-lives
      exceeded 34 and 7 days, respectively) and was also significantly more efficacious
      in preventing a catheter infection when 10(6) CFU of S. aureus was inoculated 2
      days after catheter implantation (P < 0.001). These results suggest that
      prolonged anti-infective activity on the external catheter surface provides
      improved efficacy in the prevention of infection.

PMID- 11302825
TI  - Thalidomide inhibits granulocyte responses in healthy humans after ex vivo
      stimulation with bacterial antigens.
AB  - Ingestion of thalidomide was associated with a reduction in the upregulation of
      the granulocyte activation marker CD11b and a reduced capacity to release
      elastase and lactoferrin after stimulation with lipopolysaccharide or
      lipoteichoic acid. A single oral dose of thalidomide attenuates neutrophil
      activation upon ex vivo stimulation with bacterial antigens.

PMID- 11302824
TI  - 4'-Ethynyl nucleoside analogs: potent inhibitors of multidrug-resistant human
      immunodeficiency virus variants in vitro.
AB  - A series of 4'-ethynyl (4'-E) nucleoside analogs were designed, synthesized, and
      identified as being active against a wide spectrum of human immunodeficiency
      viruses (HIV), including a variety of laboratory strains of HIV-1, HIV-2, and
      primary clinical HIV-1 isolates. Among such analogs examined, 4'-E-2'
      deoxycytidine (4'-E-dC), 4'-E-2'-deoxyadenosine (4'-E-dA), 4'-E-2'
      deoxyribofuranosyl-2,6-diaminopurine, and 4'-E-2'-deoxyguanosine were the most
      potent and blocked HIV-1 replication with 50% effective concentrations ranging
      from 0.0003 to 0.01 microM in vitro with favorable cellular toxicity profiles
      (selectivity indices ranging 458 to 2,600). These 4'-E analogs also suppressed
      replication of various drug-resistant HIV-1 clones, including HIV-1(M41L/T215Y),
      HIV-1(K65R), HIV-1(L74V), HIV-1(M41L/T69S-S-G/T215Y), and HIV
      1(A62V/V75I/F77L/F116Y/Q151M). Moreover, these analogs inhibited the replication
      of multidrug-resistant clinical HIV-1 strains carrying a variety of drug
      resistance-related amino acid substitutions isolated from HIV-1-infected
      individuals for whom 10 or 11 different anti-HIV-1 agents had failed. The 4'-E
      analogs also blocked the replication of a non-nucleoside reverse transcriptase
      inhibitor-resistant clone, HIV-1(Y181C), and showed an HIV-1 inhibition profile
      similar to that of zidovudine in time-of-drug-addition assays. The antiviral
      activity of 4'-E-thymidine and 4'-E-dC was blocked by the addition of thymidine
      and 2'-deoxycytidine, respectively, while that of 4'-E-dA was not affected by 2'
      deoxyadenosine, similar to the antiviral activity reversion feature of 2',3'
      dideoxynucleosides, strongly suggesting that 4'-E analogs belong to the family of
      nucleoside reverse transcriptase inhibitors. Further development of 4'-E analogs
      as potential therapeutics for infection with multidrug-resistant HIV-1 is
      warranted.

PMID- 11302826
TI  - Absence of mutations in marRAB or soxRS in acrB-overexpressing fluoroquinolone
      resistant clinical and veterinary isolates of Escherichia coli.
AB  - The amount of acrB, marA, and soxS mRNA was determined in 36 fluoroquinolone
      resistant E. coli from humans and animals, 27 of which displayed a multiple
      resistance phenotype. acrB mRNA was elevated in 11 of 36 strains. A mutation at
      codon 45 (Arg-->Cys) in acrR was found in 6 of these 11 strains. Ten of the 36
      isolates appeared to overexpress soxS, and five appeared to overexpress marA. A
      number of mutations were found in the marR and soxR repressor genes, correlating
      with greater amounts of marA and soxS mRNA, respectively.

PMID- 11302827
TI  - In vitro activities of six quinolones and mechanisms of resistance in
      Staphylococcus aureus and coagulase-negative staphylococci.
AB  - Of 94 clinical isolates of Staphylococcus aureus (n = 51) and coagulase-negative
      staphylococci (CNS) (n = 43), mutations in the quinolone resistance-determining
      region of topoisomerases GrlA, GrlB, GyrA, and GyrB together with MICs of six
      quinolones were analyzed. Amino acid substitutions at identical residues (GrlA
      residues 80 and 84; GyrA residues 84 and 88) were found in S. aureus and CNS.
      Active efflux, as suggested by blocking by reserpine, contributed substantially
      to the resistance phenotype in some strains. Among ciprofloxacin, clinafloxacin,
      levofloxacin, nalidixic acid, trovafloxacin, and sparfloxacin, a 0.5-microg/ml
      concentration of sparfloxacin discriminated best between strains with two or
      three mutations and those with no mutations.

PMID- 11302829
TI  - Pharmacokinetics of itraconazole oral solution in neutropenic children during
      long-term prophylaxis.
AB  - We investigated the pharmacokinetics and safety of an oral solution of
      itraconazole in two groups of neutropenic children stratified by age. Effective
      concentrations of itraconazole in plasma were reached quickly and maintained
      throughout treatment. The results indicate a trend toward higher concentrations
      of itraconazole in plasma in older children.

PMID- 11302828
TI  - Synergistic interactions between mammalian antimicrobial defense peptides.
AB  - A single animal can express several cationic antimicrobial peptides with
      different sequences and structures. We demonstrate that mammalian peptides from
      different structural classes frequently show synergy with each other and
      selectively show synergy with human lysozyme.

PMID- 11302830
TI  - Vancomycin and ceftazidime bioactivities persist for at least 2 weeks in the
      lumen in ports: simplifying treatment of port-associated bloodstream infections
      by using the antibiotic lock technique.
AB  - The residual antibiotic concentration of vancomycin (2 mg/ml)- or ceftazidime (2
      mg/ml)-heparin solutions instilled in ports in pediatric hematology-oncology
      patients 1 to 34 days earlier was measured. Antibiotic concentrations of > or =
      100 microg of either antibiotic per ml persisted for at least 21 days. For
      treatment of lumenal port infections, antibiotic-heparin dwell times of > or = 2
      weeks may be appropriate.

PMID- 11302831
TI  - In vitro activity of clarithromycin against intracellular Helicobacter pylori.
AB  - The in vitro intracellular effect of clarithromycin, amoxicillin, metronidazole,
      lansoprazole, and rifabutin, tested at concentrations corresponding to one times
      the MIC, two times the MIC, and four times the MIC, was evaluated against an
      invasive Helicobacter pylori strain. At four times the MIC, clarithromycin showed
      an early bactericidal effect within 4 h of incubation and, in determining the
      complete killing within a 16 h-incubation period, lansoprazole and rifabutin
      showed comparable activity, yielding bactericidal activities within 4 and 8 h of
      incubation, respectively. Amoxicillin and metronidazole showed bacteriostatic
      activity only.

PMID- 11302832
TI  - Tolerance and pharmacokinetic interactions of rifabutin and azithromycin.
AB  - This multicenter study evaluated the tolerance and potential pharmacokinetic
      interactions between azithromycin and rifabutin in volunteers with or without
      human immunodeficiency virus infection. Daily dosing with the combination of
      azithromycin and rifabutin was poorly tolerated, primarily because of
      gastrointestinal symptoms and neutropenia. No significant pharmacokinetic
      interactions were found between these drugs.

PMID- 11302833
TI  - Macrolide resistance in Streptococcus pneumoniae in Hong Kong.
AB  - Erythromycin resistance rates among penicillin-susceptible Streptococcus
      pneumoniae were 38 and 92% among penicillin-intermediate and -resistant S.
      pneumoniae isolates from Hong Kong, respectively, and 27% (43 of 158) of the
      isolates showed the MLS(B) phenotype, and the majority carried the ermB gene; 73%
      (115 of 158) displayed the M phenotype, and all possessed the mef gene. The
      MLS(B) phenotype was predominant in penicillin-susceptible, macrolide-resistant
      isolates and in penicillin-nonsusceptible isolates of serotype 6B, whilst the M
      phenotype was predominant in penicillin-intermediate or -resistant isolates
      belonging to serotype 23F or 19F. Extensive spread of clones of drug-resistant
      pneumococci has led to the widespread presence of macrolide resistance in S.
      pneumoniae in Hong Kong.

PMID- 11302834
TI  - Antimicrobial susceptibilities of unique Stenotrophomonas maltophilia clinical
      strains.
AB  - Susceptibility to 41 antimicrobials was studied with 99 Stenotrophomonas
      maltophilia strains, and different pulsed-field gel electrophoresis profiles were
      identified among 130 prospectively collected isolates. Moxalactam, doxycycline,
      minocycline, and clinafloxacin displayed the highest activity (> or = 98%
      susceptibility). Ticarcillin resistance (75%) was reverted by clavulanate in 25%
      of strains. Trimethoprim-sulfamethoxazole resistance was 26.2% (> or = 4
      [trimethoprim]/76 [sulfamethoxazole] microg/ml) and dropped to 11.1% when an
      8/152-microg/ml breakpoint was applied based on its bimodal MIC distribution.
      Resistance was lower when unique strains were considered, because clonal
      organisms contribute to resistance.

PMID- 11302835
TI  - Identification of beta-lactamase-negative, ampicillin-resistant strains of
      Haemophilus influenzae with four methods and eight media.
AB  - A challenge set of 143 non-beta-lactamase-producing strains of Haemophilus
      influenzae was tested for ampicillin susceptibility on two broth media and six
      agar media, using broth microdilution, agar dilution, disk diffusion, and E-test
      procedures. When beta-lactamase-negative, ampicillin-resistant (BLNAR) strains
      were defined as those for which the ampicillin MIC was > or = 4.0 microg/ml, 5 to
      44% of our selected strains were BLNAR depending on the medium and/or test method
      used. If nonsusceptible strains for which ampicillin MICs were intermediate were
      included in the BLNAR category, 32 to 50% of our isolates would be considered
      BLNAR. These data emphasize the need for a standardized testing procedure and a
      universal definition of BLNAR strains before the clinical relevance of such
      strains can be evaluated. NCCLS dilution tests with haemophilus test medium broth
      or agar are preferred for testing ampicillin against H. influenzae.

PMID- 11302836
TI  - Effect of potassium on Saccharomyces cerevisiae resistance to fluconazole.
AB  - Susceptibility of strain S288c of Saccharomyces cerevisiae to fluconazole was
      assayed in the presence and absence of KCl. Addition of 150 mM KCl renders the
      strain more sensitive to the antifungal agent. The effect is caused by the K(+)
      ion rather than the anion or the osmolarity of the medium. The increase in
      sensitivity does not modify the values of intracellular and extracellular pH
      established in the presence of KCl.

PMID- 11302837
TI  - Prevention and treatment of lethal murine endotoxemia by the novel
      immunomodulatory agent MFP-14.
AB  - Multifunctional protein 14 (MFP-14) is a ubiquitous protein that inhibits the
      production of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN
      gamma), which are involved in the pathogenesis of sepsis. Here,
      lipopolysaccharide (LPS)-induced lethality in mice was markedly reduced by MFP
      14. The treatment also lowered LPS-induced levels of TNF-alpha and IFN-gamma in
      the blood.

PMID- 11302839
TI  - Genomic and genetic relationships among species of Leymus (Poaceae: Triticeae)
      inferred from 18S-26S ribosomal genes.
AB  - The 18S-26S ribosomal genes in three closely related species of Leymus (Poaceae:
      Triticeae) were examined using fluorescence in situ hybridization (FISH) and
      restriction fragment length polymorphism (RFLP). Both approaches revealed a close
      relationship between L. arenarius (8x = 56, northern European) and L. racemosus
      (4x = 28, central Eurasian), whereas L. mollis (4x = 28, northern
      American/Pacific) was distinct. Each species had three homologous pairs of major
      rDNA loci: a1, a2, and a3 for L. arenarius; m1, m2, and m3 for L. mollis; and r1,
      r2, and r3 for L. racemosus. Leymus arenarius had in addition three minor loci,
      a4, a5, and a6. The major loci of L. arenarius and L. racemosus were identical,
      indicating that the former species could have originated from the latter, via
      interspecific hybridization and/or polyploidy. The rDNA-RFLPs further indicated
      relationships of these species to other species of Leymus (L. karellini, 8x = 56
      and L. angustus, 12x = 84) and Psathyrostachys (P. fragilis, P. huashanica, P.
      juncea, and P. lanuginosa, which are all diploids). A phenogram constructed from
      20 BamHI, EcoRI, and DraI rDNA fragments revealed closer relationship between the
      two genera, Leymus and Psathyrostachys, than that among species within a genus.

PMID- 11302838
TI  - Serotype 19f multiresistant pneumococcal clone harboring two erythromycin
      resistance determinants (erm(B) and mef(A)) in South Africa.
AB  - One hundred eighteen erythromycin-resistant Streptococcus pneumoniae (ERSP)
      strains (MICs of > or = 0.5 microg/ml) from five laboratories serving the private
      sector in South Africa were analyzed for the genes encoding resistance to
      macrolides. Sixty-seven ERSP strains (56.8%) contained the erm(B) gene, and 15
      isolates (12.7%) contained the mef(A) gene. Thirty-six isolates (30.5%) harbored
      both the erm(B) and mef(A) genes and were highly resistant to erythromycin and
      clindamycin. DNA fingerprinting by BOX-PCR and pulsed-field gel electrophoresis
      identified 83% of these strains as belonging to a single multiresistant serotype
      19F clone.

PMID- 11302840
TI  - Ontogenetic wood anatomy of tree and subtree species of Nepalese Rhododendron
      (Ericaceae) and characterization of shrub species.
AB  - Ontogenetic trends in the wood structure of Nepalese Rhododendron were studied in
      15 specimens of two tree and four subtree species. Average growth ring width was
      constant from pith to bark in spite of occurrences of extremely narrow, false, or
      discontinuous rings. Vessel density, vessel area, vessel element length, and
      multiseriate ray height generally had an initial increase or decrease to 1.5 cm
      radius and near plateau or slight decrease or increase outward. Multiseriate ray
      density and area percentage were variable between specimens without a clear
      pattern. Ontogenetic trends from pith to fully mature wood in trees plus subtrees
      were inferred by treating the measurements in the present study with those of
      mature individuals in a previous study. Comparison of trends in trees plus
      subtrees and those in shrubs lead to ecological or systematic groupings. Vessel
      features showed that alpine shrub species have distinctly small, numerous vessels
      composed of short vessel elements. Multiseriate ray features indicated a
      systematic difference between the trees plus subtrees of subgenus Hymenanthes and
      the shrubs of subgenus Rhododendron. Vessel features of alpine shrubs may be an
      adaptation against frequent freeze-thaw cycles or the result of growth stress
      imposed by the severe alpine environment.

PMID- 11302841
TI  - An expanded role for the TWN1 gene in embryogenesis: defects in cotyledon pattern
      and morphology in the twn1 mutant of Arabidopsis (Brassicaceae).
AB  - The suspensor is a specialized basal structure that differentiates early in plant
      embryogenesis to support development of the embryo proper. Suspensor
      differentiation in Arabidopsis is maintained in part by the TWIN1 (TWN1) gene,
      which suppresses embryogenic development in suspensor cells: twn1 mutants produce
      supernumerary embryos via suspensor transformation. To better understand
      mechanisms of suspensor development and further investigate the function of TWN1,
      we have characterized late-embryo and post-embryonic development in the twn1
      mutant, using seedling culture, microscopy, and genetics. We report here that the
      twn1 mutation disrupts cotyledon number, arrangement, and morphology and
      occasionally causes partial conversion of cotyledons into leaves. These defects
      are not a consequence of suspensor transformation. Thus, in addition to its basal
      role in suspensor differentiation, TWN1 influences apical pattern and morphology
      in the embryo proper. To determine whether other genes can similarly affect both
      suspensor and cotyledon development, we looked for twinning in Arabidopsis
      mutants previously identified by their abnormal cotyledon phenotypes. One such
      mutant, amp1, produced a low frequency of twin embryos by suspensor
      transformation. Our results suggest that mechanisms that maintain suspensor
      identity also function later in development to influence organ formation at the
      embryonic shoot apex. We propose that TWN1 functions in cell communication
      pathways that convey local positional information in both the apical and basal
      regions of the Arabidopsis embryo.

PMID- 11302842
TI  - Comparative evaluation of vessel elements in S alix spp. (Salicaceae) endemic to
      the Athabasca sand dunes of northern Saskatchewan, Canada.
AB  - Vessel element (VE) characters, including density, lumen diameter, length, and
      clustering, were evaluated using light and scanning electron microscopy in four
      endemic Salix taxa from the Lake Athabasca sand dunes in northern Saskatchewan,
      Canada. These data were compared with the widespread putative sister species for
      each endemic. Endemic taxa exhibited similar VE densities as compared to their
      associated sister species. Salix brachycarpa var. brachycarpa and its derived
      endemic, var. psammophila, had the highest VE density values of all endemic
      progenitor pairs in this study. Values for VE lumen diameter and VE length were
      significantly different in some of the species pairs. Lumen diameter of the
      endemic S. planifolia ssp. tyrrelli was significantly less than that of its
      widespread sister species, ssp. planifolia. Salix turnorii had significantly
      greater values for both VE lumen diameter and length than its progenitor, S.
      lutea. Vessel element clustering did not differ significantly between endemic and
      progenitor taxa with the exception of S. silicicola and its arctic progenitor, S.
      alaxensis. Structural differences for these endemic willows appear related to
      their open sand habitat, and taxonomic implications for endemic-progenitor pairs
      are discussed.

PMID- 11302843
TI  - A genetic analysis of hydrologically dispersed seeds of Hibiscus moscheutos
      (Malvaceae).
AB  - The dispersal of floating seeds in wetland habitats should influence the genetic
      characteristics of plant metapopulations. We examined gene flow of a hydrochorous
      wetland macrophyte, Hibiscus moscheutos L. (Malvaceae), by analyzing allozyme
      variation in current-year floating-seed populations. The genetic composition of
      floating seeds was compared to the genetic composition of established populations
      of H. moscheutos that had been previously analyzed in the same areas. The F
      statistics demonstrated that genetic structuring among floating-seed populations
      was weak or absent, indicating that seeds from source populations were thoroughly
      mixed. Floating-seed populations had an excess of homozygotes, a different
      situation than had previously been found in established populations. The exchange
      of seeds was greatest among H. moscheutos populations that were adjacent to a
      tidal stream. We conclude that populations adjacent to the tidal streams are part
      of a metapopulation that serves as a reserve of genetic variation in the system.
      Although established populations of H. moscheutos that are not close to the tidal
      stream are relatively isolated genetically, we found evidence that they also
      contribute to the floating-seed populations within the estuary.

PMID- 11302844
TI  - Spatiotemporal dynamics of Floerkea proserpinacoides (Limnanthaceae), an annual
      plant of the deciduous forest of eastern North America.
AB  - Because environmental filters are temporally and spatially heterogeneous, there
      often is a lack of significant relationship between the spatial patterns of
      successive life stages in plant populations. In this study, we determined the
      spatiotemporal relationships between different life stages in two populations of
      an annual plant of the deciduous forests of eastern North America, Floerkea
      proserpinacoides. Demographic surveys were done over a 4-yr period, and
      experiments were performed in the field and under controlled conditions to test
      for the effects of various environmental factors on population dynamics. There
      was a general lack of relationship between the spatial patterns of seed bank and
      seedling density, and a lack of similarity between their spatial correlograms.
      This was related mostly to the effects of spatially variable environmental
      filters operating on germination and emergence. However, environmental filters
      acting on plant survival were stable through time and contributed to stabilize
      the density and spatial patterns of the populations. Despite density-dependent
      presenescence mortality, spatial patterns of seedlings and mature individuals
      were similar and their correlograms were alike, suggesting that mortality did not
      fully compensate for density. Estimated fecundity was negatively correlated with
      population density over the study period. Although flower production started only
      2-3 wk after emergence, seed maturation mostly occurred at the end of the life
      cycle, just before the onset of plant senescence. Yet, individual fecundity was
      low for an annual plant, i.e., 3.0 +/- 0.5 mature seeds/plant (mean +/- 1 SE).
      Seed predation by vertebrates was not significant. Low soil moisture had little
      effect on the total number of seeds germinating, although it slowed down the
      germination process. In quadrats where leaf litter was experimentally doubled,
      seedling emergence was lower than in control quadrats; in quadrats where leaf
      litter was completely removed, emergence did not differ from that in control
      quadrats. Susceptibility to drought stress was higher for seedlings than for
      mature plants. Although the species does not maintain a long-term persistent soil
      seed bank, other factors, such as density-dependent fecundity and autogamy, may
      temper population fluctuations through time and reduce the probability of local
      extinction.

PMID- 11302845
TI  - Genetic relationships and population structure of the endangered Steamboat
      buckwheat, Eriogonum ovalifolium var. williamsiae (Polygonaceae).
AB  - Eriogonum ovalifolium var. williamsiae (Steamboat buckwheat) is a narrow endemic
      subshrub, known from a single locality in Washoe County, Nevada. We examined
      genetic structure of the only known population by analyzing patterns of allozyme
      variation. Our results suggest that Steamboat buckwheat has high genetic
      variability, with levels of variation similar to that typical of a widespread
      species rather than a narrow endemic. Genotype frequencies suggest that mating is
      random. We detected no genetic subdivision of the population. Several clones
      spanning up to 67 cm were found, but we do not know if such clones are common. We
      used allozyme data to assess the genetic similarity of var. williamsiae to five
      other varieties of E. ovalifolium. All six varieties are very similar
      allozymically with var. williamsiae being the most similar to the widespread var.
      ovalifolium. Although var. williamsiae and var. ovalifolium are morphologically
      distinct, their genetic similarity warrants further study to determine whether or
      not they should be treated as separate taxa. Evidence of male sterility in var.
      williamsiae plus other data leads us to hypothesize that this taxon might be
      either a hybrid or undergoing cytoplasmic introgression. Information gathered
      from this study, in concert with ongoing work on the breeding system of Steamboat
      buckwheat, should be helpful in forming management strategies for this plant.

PMID- 11302846
TI  - Effects of virus infection and light environment on population dynamics of
      Eupatorium makinoi (Asteraceae).
AB  - We studied the effects of virus infection on dynamics of three Eupatorium makinoi
      populations in contrasting light environments, Gora-dani (a shaded population)
      and Minou 1 and Minou 2 (open-site populations). Censuses of the plants were
      taken for 8 yr in Gora-dani and 4 yr in Minou 1 and Minou 2. After the epidemics
      of virus infection, most plants were virus infected at both sites. The number of
      plants and the proportion of flowering individuals decreased rapidly and
      simultaneously in the shaded population in Gora-dani. By contrast, in the open
      site populations of Minou, the proportion of flowering plants decreased first,
      and then the number of plants decreased gradually. Growth analysis of the plants
      in the Gora-dani population revealed that stem growth was significantly
      suppressed by infection and that flowering and survivorship of the infected
      plants decreased with reducing plant height. Since light availability affected
      plant growth and thereby flowering and survivorship, the differences in
      population dynamics between the two field sites could be caused by the
      differences in light environments. Although populations in open sites may persist
      for considerable periods after virus epidemics, the individual local populations
      of E. makinoi would eventually become extinct irrespective of light environments.

PMID- 11302847
TI  - Seed size variation and predation of seeds produced by wild and crop-wild
      sunflowers.
AB  - The movement of pollen between crop and wild sunflowers (both Helianthus annuus)
      has led to concerns about the possible introduction of crop transgenes into wild
      populations. The persistence of crop traits in wild populations will depend in
      part on the relative fitness of crop-wild hybrid vs. wild plants. Using seeds
      from two large experimental field plots, we found that seeds produced by crop
      wild plants were twice the size of wild seeds and differed in coloration. Head
      diameter, date of flowering, identity of mother plant, and levels of predispersal
      predation explained some variation in mean seed size. We hypothesized that
      postdispersal vertebrate seed predation would be affected by seed size, with
      hybrid seeds preferentially eaten. In each of three field trials, significantly
      more hybrid seeds were eaten (62% of hybrid seed; 42% of wild seed). Within the
      category of wild seeds, larger seeds were preferentially eaten; however among
      hybrid seeds, predation was not significantly related to seed size. In this
      study, differential predation thus reduces hybrid fitness and would presumably
      slow the spread of transgenes into wild populations.

PMID- 11302848
TI  - Time to chill: effects of simulated global change on leaf ice nucleation
      temperatures of subarctic vegetation.
AB  - We investigated the effects of long-term (7-yr) in situ CO(2) enrichment (600
      MUmol/mol) and increased exposure to UV-B radiation, the latter an important
      component of global change at high latitudes, on the ice nucleation temperatures
      of leaves of several evergreen and deciduous woody ericaceous shrubs in the
      subarctic (68 degrees  N). Three (Vaccinium uliginosum, V. vitis-idaea, and
      Empetrum hermaphroditum) of the four species of shrubs studied showed
      significantly higher ice nucleation temperatures throughout the 1999 growing
      season in response to CO(2) enrichment and increased exposure to UV-B radiation
      relative to the controls. The same species also showed a strong interactive
      effect when both treatments were applied together. In all cases, leaves cooled to
      below their ice nucleation temperatures failed to survive the damage resulting
      from intracellular ice formation. Our results strongly suggest that future global
      change on a decadal time scale (atmospheric CO(2) increases and polar
      stratospheric O(3) destruction) will lead to increased foliage damage of
      subarctic vegetation by severe late spring or early autumnal frosting events.
      Indeed, in support of our experimental findings, there is now some evidence that
      increases in atmospheric CO(2) concentration over the past three to four decades
      may already have acted in this manner on high-elevation arboreal plants in the
      Swedish Scandes. The implications for vegetation modeling in a future
      "greenhouse" world and palaeoclimate estimates from high-latitude plant fossils
      dating to the high-CO(2) environment of the Mesozoic are discussed.

PMID- 11302849
TI  - Patterns of leaf-pathogen infection in the understory of a Mexican rain forest:
      incidence, spatiotemporal variation, and mechanisms of infection.
AB  - This study assessed the levels of damage by leaf pathogens and their variability
      in terms of host species, space (four mature forest sites) and season of the year
      (dry and rainy), and the mechanisms of infection in the understory of the Los
      Tuxtlas tropical rain forest. Sixty-five percent of the species surveyed in the
      dry season (N = 49) and 64.9% of those surveyed in the rainy season (N = 57) were
      damaged by fungi. Leaf area damaged per plant, on average, was <1% (range: 0.25
      20.52%). There was considerable variation in the degree of infection among
      species, but not among sites and seasons. The survey showed that 43% of the
      leaves were damaged by herbivores and pathogens concurrently, 16% showed damage
      by insect herbivory alone, and only 1.4% of the sampled leaves showed damage by
      pathogens alone. Pathogenicity assays experimentally confirmed that the
      predominant mechanism of fungal establishment was wounding, such as that caused
      by herbivory (or other similar sources), and only rarely did infection occur
      through direct contact (without wounds). The results revealed the omnipresence of
      leaf fungal infection, although with low damage per plant, and the importance of
      herbivorous insects in the facilitation of fungal infection in tropical
      understory plants.

PMID- 11302850
TI  - Partial cambial mortality in high-elevation Pinus aristata (Pinaceae).
AB  - Partial cambial mortality is a growth form that is characteristic of Pinus
      aristata trees. To better elucidate their cambial death pattern, tree size and
      aspect of cambial death data were gathered from three Pinus aristata forests in
      central Colorado, USA. Stripping frequency tended to be higher for larger
      diameter classes. Partial cambial mortality exhibits significant directionality
      within each stand. Furthermore, cambial death was measured to be most frequent on
      the wind-exposed side of stripped trees in two of the three study sites and
      appeared to be at the third. Data presented here support the hypothesis that wind
      plays a role in the occurrence of partial cambial mortality in Pinus aristata.
      The mechanisms by which wind causes cambial mortality remain unclear.

PMID- 11302851
TI  - Field measurements of internal pressurization in Phragmites australis (Poaceae)
      and implications for regulation of methane emissions in a midlatitude prairie
      wetland.
AB  - Emergent aquatic macrophytes in vegetated wetlands provide routes for methane
      (CH(4)) transport from sites of production in oxygen-poor sediments, where CH(4)
      concentrations are relatively high, to the atmosphere, which typically has much
      lower CH(4) concentrations. Transport can occur through aerenchymatous tissue via
      simple diffusion. Recently, the importance of convective throughflow (i.e., mass
      transport of gases through plants driven by pressure gradients) in enhancing gas
      transport has been demonstrated in several genera (e.g., Nuphar, Nymphaea,
      Nelumbo, Typha, and Phragmites). This study was conducted to elucidate the
      governing plant-mediated gas transport mechanisms in a midlatitude prairie
      wetland and to determine both their diel and seasonal variations and the
      importance of environmental controlling factors. Pressures inside culms of the
      two dominant emergent aquatic macrophytes (Scirpus acutus and Phragmites
      australis) were measured directly throughout the growing season and on selected
      days in midseason. Supporting measurements included solar radiation, air
      temperature, relative humidity, and windspeed. Results indicated pressures inside
      green healthy culms of Phragmites were above atmospheric pressure by up to 1650
      Pa during the day. At night culm pressures were at or slightly above atmospheric.
      No pressurization was detected in Scirpus. Highest pressures in Phragmites
      occurred during midseason when biomass and foliage area index were at their
      maxima (920 g/m(2) and 2.8, respectively). High internal pressures also coincided
      with periods of high solar radiation (>500 W/m(2)), high temperature (>20 degrees
      C), and low relative humidity (<60%). Periods of high internal pressures also
      coincided with periods of high CH(4) efflux from the wetland as measured in
      concomitant studies. Convective throughflow driven by internal pressure gradients
      in Phragmites thus explains much of the diel variation in methane efflux
      previously reported from this wetland.

PMID- 11302852
TI  - Different cost of reproduction for the males and females of the rare dioecious
      shrub Corema conradii (Empetraceae).
AB  - Males and females of dioecious plant species often differ in their reproductive
      investment. Such differences frequently result in differential demographic costs
      represented by lower growth, survival, and/or frequency of reproduction, and/or
      by more variable reproductive effort through time for females. We present the
      results of a study on Corema conradii, a rare dioecious shrub of the coastal dune
      heathlands of northeastern North America. We estimated the reproductive
      investment of both males and females, determined their age structure, and
      compared their spatial patterns in a population at Iles-de-la-Madeleine, Quebec.
      We also determined the sex ratio of the four populations known to occur on the
      islands. Males invested more in reproduction at flowering, but when fruit
      production was considered, female reproductive investment was higher in terms of
      biomass, Mg, and Ca, but not in terms of N, P, and K. The age frequency
      distribution of males and females did not differ significantly from one another.
      The population dispersion pattern was contagious, with patches of similar-age
      individuals. There was no spatial segregation between males and females, although
      the sex ratio varied somewhat spatially. Females did not start reproducing at a
      later age than males and did not appear to have a shorter longevity. However, the
      crown and radial growth rates of females were lower than those of males. When
      estimated by the crown intercept method, the sex ratio of all four populations
      was male biased. However, because males had a higher crown growth rate, genet sex
      ratio was in fact balanced. Higher investment in reproduction was associated with
      a lower growth rate, which represents a differential cost of reproduction
      according to sex in this species.

PMID- 11302853
TI  - Spectral reflectance of Picea rubens (Pinaceae) and Abies balsamea (Pinaceae)
      needles along an elevational gradient, Mt. Moosilauke, New Hampshire, USA.
AB  - Relationships among elevation, foliar morphology, spectral reflectance, and
      chlorophyll fluorescence of two co-occurring montane conifers, red spruce (Picea
      rubens Sarg.) and balsam fir (Abies balsamea [L.] Mill.), were investigated along
      two transects from 460 to 1460 m on Mt. Moosilauke in the White Mountains of New
      Hampshire, USA. Spectral reflectance (300-1100 nm wavelengths) and the
      chlorophyll fluorescence F(v)/F(m) ratio were measured on dark-adapted needles.
      Foliar morphology (needle size, shape, and mass) and nitrogen concentrations were
      measured in the laboratory. Reflectance spectra varied between species and with
      elevation. Two chlorophyll measures, red edge position and a chlorophyll-based
      difference index (Chl NDI = R750 - R705/R750 + R705), indicated more chlorophyll
      in fir than in spruce and decreasing chlorophyll with increasing elevation in
      both species. The structure-independent pigment index (SIPI = R800 - R445/R800 -
      R680) increased with elevation, indicating an increasing carotenoid : chlorophyll
      ratio. The photochemical reflectance index (PRI = R531 - R570/R531 + R570), a
      measure of photosynthetic radiation use efficiency, decreased with increasing
      elevation up to 1370 m. In the highest elevation site, within the stunted alpine
      krummholz at 1460 m, PRI was higher than at 1370 m, but still lower than at 1070
      m. This same pattern was evident in the chlorophyll fluorescence F(v)/F(m)
      measurements. These independent indices indicate higher stress in spruce than
      fir, which may be related to the "spruce decline" reported in the northeastern
      USA. Results also indicate progressively increasing stress with increasing
      elevation up to 1370 m. Stress appears to be lower at 1460 m than at 1370 m,
      despite the harsher conditions at the very summit of Mt. Moosilauke. This may be
      a consequence of stress-tolerant physiology and/or prostrate architecture.

PMID- 11302854
TI  - Leaf optical properties in higher plants: linking spectral characteristics to
      stress and chlorophyll concentration.
AB  - A number of studies have linked responses in leaf spectral reflectance,
      transmittance, or absorptance to physiological stress. A variety of stressors
      including dehydration, flooding, freezing, ozone, herbicides, competition,
      disease, insects, and deficiencies in ectomycorrhizal development and N
      fertilization have been imposed on species ranging from grasses to conifers and
      deciduous trees. In all cases, the maximum difference in reflectance within the
      400-850 nm wavelength range between control and stressed states occurred as a
      reflectance increase at wavelengths near 700 nm. In studies that included
      transmittance and absorptance as well as reflectance, maximum differences
      occurred as increases and decreases, respectively, near 700 nm. This common
      optical response to stress could be simulated closely by varying the chlorophyll
      concentration of model leaves (fiberglass filter pads) and by the natural
      variability in leaf chlorophyll concentrations in senescent leaves of five
      species. The optical response to stress near 700 nm, as well as corresponding
      changes in reflectance that occur in the green-yellow spectrum, can be explained
      by the general tendency of stress to reduce leaf chlorophyll concentration.

PMID- 11302855
TI  - Self-pollination and its costs in a monoecious fig (Ficus aurea, Moraceae) in a
      highly seasonal subtropical environment.
AB  - The unusual floral phenology of most monoecious figs, related to their highly
      specialized pollination mutualism with agaonid wasps, combines pronounced
      dichogamy at the level of inflorescences and individuals with population-level
      asynchrony in flowering. This floral phenology ensures that outcrossing strongly
      predominates. Fig populations may thus be expected to possess deleterious
      recessive alleles that lead to inbreeding depression when selfing does occur.
      However, whether monoecious figs are self-compatible and whether selfing results
      in inbreeding depression have never been investigated. Using wasps as
      "pollination tools" and exploiting infrequent overlap in male and female phases
      on the same tree, we conducted controlled selfed and outcrossed pollination
      experiments in Ficus aurea. Our results show that this species is totally self
      compatible. No negative effects of selfing could be demonstrated on syconium
      retention, number of vacant ovaries, seed set, or seed germination. However, wasp
      production had a tendency to be higher after self-pollination. While it is
      possible that inbreeding depression is expressed at later developmental stages,
      its absence at the early stages we examined is nonetheless surprising for a plant
      expected to be highly outcrossed. It is likely that selection pressures other
      than avoidance of inbreeding are responsible for the evolution and maintenance of
      the unusual floral phenology of figs.

PMID- 11302856
TI  - Chromosome numbers and pollen stainability of three species of Pacific Island
      breadfruit (Artocarpus, Moraceae).
AB  - Chromosome numbers were determined for 48 accessions of breadfruit (Artocarpus
      altilis, A. mariannensis, and A. camansi [Moraceae]) from 16 Pacific Island
      groups, Indonesia, and the Philippines. Artocarpus camansi and A. mariannensis
      exhibit counts of 2n = 56; 2n = 56 (diploidy) and 2n = 84 (triploidy) were
      observed for A. altilis. Most diploid cultivars of A. altilis were seeded, but
      two cultivars with reduced seed number were observed. Micronesian accessions
      included putative interspecific hybrids between A. altilis and A. mariannensis.
      The majority of these accessions were seedless diploids, but triploid putative
      hybrids were also observed. Pollen stainablility was shown to correlate with the
      degree of seediness.

PMID- 11302857
TI  - Molecular phylogenetics of Acacia (Fabaceae: Mimosoideae) based on the
      chloroplast MATK coding sequence and flanking TRNK intron spacer regions.
AB  - The tribe Acacieae (Fabaceae: Mimosoideae) contains two genera, the monotypic
      African Faidherbia and the pantropical Acacia, which comprise about 1200 species
      with over 950 confined to Australia. As currently recognized, the genus Acacia is
      subdivided into three subgenera: subg. Acacia, subg. Aculeiferum, and the
      predominantly Australian subg. Phyllodineae. Morphological studies have suggested
      the tribe Acacieae and genus Acacia are artificial and have a close affinity to
      the tribe Ingeae. Based on available data there is no consensus on whether Acacia
      should be subdivided. Sequence analysis of the chloroplast trnK intron, including
      the matK coding region and flanking noncoding regions, indicate that neither the
      tribe Acacieae nor the genus Acacia are monophyletic. Two subgenera are
      monophyletic; section Filicinae of subgenus Aculeiferum does not group with taxa
      of the subgenus. Section Filicinae, eight Ingeae genera, and Faidherbia form a
      weakly supported paraphyletic grade with respect to subg. Phyllodineae. Acacia
      subg. Aculeiferum (s. s.) is sister to the grade. These data suggest that
      characters currently used to differentiate taxa at the tribal, generic, and
      subgeneric levels are polymorphic and homoplasious in cladistic analyses.

PMID- 11302858
TI  - Phylogeny and patterns of floral diversity in the genus Piper (Piperaceae).
AB  - With ~1000 species distributed pantropically, the genus Piper is one of the most
      diverse lineages among basal angiosperms. To rigorously address the evolution of
      Piper we use a phylogenetic analysis of sequences of the internal transcribed
      spacers (ITS) of nuclear ribosomal DNA based on a worldwide sample. Sequences
      from a total of 51 species of Piper were aligned to yield 257 phylogenetically
      informative sites. A single unrooted parsimony network suggested that taxa
      representing major geographic areas could potentially form three monophyletic
      groups: Asia, the South Pacific, and the Neotropics. The position of Pothomorphe
      was well supported among groups of New World taxa. Simultaneous phylogenetic
      analysis of an expanded alignment including outgroups suggested that taxa from
      the South Pacific and Asia formed a monophyletic group, provisionally supporting
      a single origin of dioecy. Within the Neotropical sister clade, resolution was
      high and strong bootstrap support confirmed the monophyly of several
      traditionally recognized infrageneric groups (e.g., Enckea [including
      Arctottonia], Ottonia, Radula, Macrostachys). In contrast, some of the species
      representing the highly polytypic subgroup Steffensia formed a clade
      corresponding to the previously recognized taxon Schilleria, while others were
      strongly associated with several of the more specialized groups of taxa. The
      distribution of putatively derived inflorescence and floral character states
      suggested that both umbellate and solitary axillary inflorescences have multiple
      origins. Reduction in anther number appears to be associated with highly packaged
      inflorescences or with larger anther primordia per flower, trends that are
      consistent with the suppression of later stages of androecial development.

PMID- 11302859
TI  - Phylogenetic relationships in family Magnoliaceae inferred from ndhF sequences.
AB  - The ndhF sequences of 99 taxa, representing all sections in extant Magnoliaceae,
      were analyzed to address phylogenetic questions in the family. Magnolia
      macrophylla and M. dealbata, North American species of Magnolia section
      Rytidospermum, are placed at the base in the subfamily Magnolioideae although its
      supporting value is low. In the remaining taxa, several distinctive lineages are
      recognized: (1) Magnolia, the biggest genus in the family, is not monophyletic;
      (2) Michelia, including section Maingola of Magnolia subgenus Magnolia, is
      closely related with Elmerrillia and sections Alcimandra and Aromadendron of
      Magnolia subgenus Magnolia; (3) the associates of Michelia are grouped with
      Magnolia subgenus Yulania and section Gynopodium of Magnolia subgenus Magnolia;
      (4) Pachylarnax forms a clade with sections Manglietiastrum and Gynopodium of
      Magnolia; (5) a well-supported Manglietia clade is recognized; (6) Caribbean
      species of section Theorhodon of Magnolia subgenus Magnolia, which are section
      Splendentes sensu Vazquez-Garcia, are closely allied with New World members of
      Magnolia subgenus Talauma; and (7) section Rytidospermum of Magnolia subgenus
      Magnolia and subgenus Talauma are polyphyletic. The separated clades in the
      molecular tree are considerably different from traditional taxonomic dispositions
      in the family. The molecular data strongly suggest that a taxonomic realignment
      of infrafamilial delimitations and compositions should be considered.

PMID- 11302860
TI  - Leaf dimorphism in Archaeopteris roemeriana (Progymnosperm): further early fossil
      evidence of shoot dorsiventrality.
AB  - Additional information on the morphology of the vegetative ultimate branches of
      Archaeopteris roemeriana was obtained by uncovering compression specimens
      collected in Upper Devonian deposits in Belgium. For the first time, anisophylly,
      previously inferred from anatomical studies, is demonstrated on one species of
      the genus. Small leaves less than half the size of those more readily seen in
      unprepared compressions are borne on the adaxial surface of the ultimate
      branches. The phyllotaxis is discussed and the eventual adaptation to light
      interception of the combination of anisophylly and shoot dorsiventrality is put
      forward.

PMID- 11302861
TI  - Cancer and autoimmunity: autoimmune and rheumatic features in patients with
      malignancies.
AB  - OBJECTIVES: To review the autoimmune and rheumatic manifestations of patients
      with malignancy. METHODS: A Medline search of all published papers using keywords
      related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic
      syndromes. RESULTS: Patients with malignant diseases may develop autoimmune
      phenomena and rheumatic diseases as a result of (a) generation of autoantibodies
      against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb),
      tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1,
      D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis
      antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated
      antigens (RNP, Sm). The clinical significance of the various autoantibodies is
      not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are
      detected before the diagnosis of the cancer or in the early stages of the
      malignant disease, suggesting a potential diagnostic or prognostic role. Anti
      onconeural antibodies are pathogenic and are associated with specific clinical
      neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic
      syndromes, a wide range of clinical syndromes, including classic autoimmune
      rheumatic diseases that develop among patients with cancer. (c) Rheumatism after
      chemotherapy, a clinical entity characterised by the development of
      musculoskeletal symptoms after combination chemotherapy for malignancy.
      CONCLUSION: Autoimmune and rheumatic features are not rare among patients with
      malignancies. They are the result of various diverse mechanisms and occasionally
      they may be associated with serious clinical entities.

PMID- 11302864
TI  - Incidence of clinically manifest ulcers and their complications in patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed
      in patients with rheumatoid arthritis (RA). Because of its frequency and
      severity, NSAID gastropathy is the most important side effect. The clinical
      spectrum of NSAID gastropathy includes gastrointestinal complaints, ulcers and
      their complications. To reduce NSAID gastropathy, rheumatologists in greater
      Amsterdam decided in January 1997 that prophylactic agents should be prescribed
      for patients with RA at high risk for NSAID gastropathy, defined as age 60 or
      older or a history of gastrointestinal (GI) ulcers, or both. OBJECTIVE: To
      determine the incidence of clinically manifest ulcers and their complications in
      patients with RA at high risk for NSAID gastropathy during a period in which
      prophylaxis was recommended. Published reports show that the incidence of
      clinically manifest ulcers and their complications varies from 1.3% to 5%.
      PATIENTS AND METHODS: Within one year, three questionnaires were sent to all
      outpatients with RA of our clinic (n=2680). The patients were asked if they had
      had a gastroscopy and/or complication of an ulcer in the preceding months. When a
      GI event (ulcer or complication) had occurred an analysis was carried out to
      determine whether the event was possibly related to a compliance failure or a
      policy failure-for example, no prophylaxis prescribed when it was recommended.
      RESULTS: The response rate for the three questionnaires was 88%, 76%, and 77%,
      respectively. All three questionnaires were returned by 1856 patients; NSAIDs
      were used in 1246 (67%) of them. Of the NSAID users 731 (59%) were in the high
      risk group. Clinically manifest ulcers occurred in seven high risk NSAID users
      (four gastric ulcers, two duodenal ulcers, and in one patient both types of
      ulcer). Complications of ulcers were diagnosed in eight (other) patients: seven
      (upper) GI bleedings and one perforation. Thus the incidence during one year of
      clinically manifest ulcers in the high risk group was 1.0% and of complications
      of ulcers 1.1%, together 2.1%. In the group of 15 patients with GI events, only
      one patient had not taken the adequately prescribed gastroprotective drugs
      (compliance failure). Misguidedly, gastroprotective drugs were not prescribed in
      seven patients (policy failure), but in the remaining seven patients
      gastroprotective drugs were adequately prescribed and used. CONCLUSION: The
      incidence of clinically manifest ulcers and of complications of ulcers in
      patients with RA at high risk for NSAID gastropathy is relatively low, and might
      be related to our strategy to prescribe prophylactic agents in these patients.

PMID- 11302865
TI  - Outcome of cervical spine surgery in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Cervical spine instability in patients with rheumatoid arthritis (RA)
      may lead to cervical myelopathy or occipital neuralgia, or both. Morbidity and
      mortality in patients with RA treated with cervical spine surgery during two
      years of follow up were evaluated. METHODS: Between 1992 and 1996 55 patients
      with RA underwent cervical spine surgery because of occipital neuralgia or
      cervical myelopathy, or both. Patients were classified according to the Ranawat
      criteria for pain and neurological assessment before operation and three months
      and two years postoperatively. For occipital neuralgia a successful operation was
      defined as complete relief of pain and for cervical myelopathy as neurological
      improvement. RESULTS: Occipital neuralgia was present in 17 patients, cervical
      myelopathy in 14 patients, and 24 had both. Surgical treatment in the patients
      with symptoms of occipital neuralgia who were still alive two years after surgery
      was successful in 18/29 (62%). In the surviving patients with cervical myelopathy
      neurological improvement of at least one Ranawat class was seen in 16/24 (67%).
      Postoperative mortality within six weeks was 3/51 (6%). Within two years after
      the operation 14 /51 (27%) of the patients had died; in most patients the cause
      of death was not related to surgery. The highest mortality (50%) was found in the
      group of six patients with quadriparesis and very poor functional capacity
      (Ranawat IIIB). CONCLUSION: Cervical spine surgery in patients with RA performed
      because of occipital neuralgia or cervical myelopathy, or both, is successful in
      most patients who are alive two years after surgery. However, the mortality rate
      during these two years is relatively high, which seems to be largely related to
      the severity of the underlying disease and not to the surgery itself.

PMID- 11302866
TI  - Treatment strategy, disease activity, and outcome in four cohorts of patients
      with early rheumatoid arthritis.
AB  - OBJECTIVE: To compare four different inception cohorts of patients with early
      rheumatoid arthritis (RA) with respect to treatment strategies, disease activity,
      and outcome during a five year follow up period. METHOD: Data from cohorts of
      patients with early RA, with a standardised assessment at least every six months
      for five years from four different centres, were included in one database. Owing
      to slight differences in the individual study designs, linearly interpolated
      values were calculated to complete the standard follow up schedule. RESULTS:
      Despite similar inclusion criteria, significant differences in demographic
      factors and baseline disease activity were found between the different cohorts.
      During the follow up an aggressive treatment strategy was followed in the Dutch
      and Finnish cohort, an intermediate strategy in the British cohort, and a
      conservative strategy in the Swedish cohort. A significant improvement in disease
      activity was seen in all cohorts, though the most rapid and striking improvement
      was seen in those receiving aggressive treatment. This resulted in less
      radiographic destruction in the long run. CONCLUSION: This observational study of
      cohorts of patients with early RA confirms that early aggressive treatment
      results not only in a more rapid reduction of disease activity but also in less
      radiographic progression in the long term.

PMID- 11302867
TI  - Prevalence and clinical significance of antikeratin antibodies and other
      serological markers in Lithuanian patients with rheumatoid arthritis.
AB  - OBJECTIVES: To assess the clinical value of several serological markers in
      Lithuanian patients with rheumatoid arthritis (RA) compared with control patients
      with rheumatic disease and age matched healthy controls. METHODS: Serum samples
      from 96 patients with RA of approximately 8 years' duration, 90 rheumatic disease
      controls, and 37 healthy subjects were tested. Antikeratin antibody (AKA),
      antineutrophil cytoplasmic antibody (ANCA), and antinuclear antibody (ANA) titres
      were estimated by indirect immunofluorescence (IIF) and serum samples positive
      for ANA and ANCA were further studied by enzyme linked immunosorbent assay
      (ELISA). IgA and IgM rheumatoid factors (RF) were measured by ELISA. RESULTS: A
      positive AKA test was highly specific for RA (diagnostic specificity 97%), being
      found in 44% of the patients. Although both RF tests had a higher sensitivity,
      they were less specific for RA. ANCA was detected in 33% of patients with RA but
      lacked diagnostic specificity. AKA and ANCA were associated with more erosive
      disease and the presence of extra-articular manifestations. Positivity for AKA,
      IgA RF, and ANCA was significantly associated with disease activity and worse
      functional capacity. However, in multiple regression analysis only positivity for
      AKA was significantly correlated with functional disability (p=0.0001), evaluated
      by the Steinbrocker functional classification, and no single marker had any
      relation with radiological damage. CONCLUSION: Although AKA showed the highest
      disease specificity, all serological markers studied except ANA exhibited
      interesting associations with important clinical and paraclinical parameters of
      RA.

PMID- 11302868
TI  - A longitudinal cohort study of Finnish patients with primary Sjogren's syndrome:
      clinical, immunological, and epidemiological aspects.
AB  - OBJECTIVE: To evaluate outcome in a cohort of Finnish patients with primary
      Sjogren's syndrome (pSS). METHODS: Clinical and laboratory data from the time of
      diagnosis and follow up were collected from 110 patients with pSS (107 women,
      three men) diagnosed in 1977-1992 in central Finland. The standardised incidence
      ratio for cancers was determined as the ratio of the observed number of cases to
      the expected number based on regional population rates. Eighty one of the 93
      patients still alive were interviewed, and clinical and laboratory examinations
      performed in 1994-1997. RESULTS: The mean (SD) erythrocyte sedimentation rate (33
      (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM
      (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001)
      lower than those at baseline. A similar change was observed in a subgroup of
      patients never treated with glucocorticosteroids or disease modifying
      antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised
      incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression
      model, the patients with pSS with subsequent lymphoma were found to have higher
      baseline levels of serum beta2 microglobulin than the others (odds ratio 1.9; 95%
      confidence interval 1.1 to 3.4). CONCLUSION: The results suggest that mean
      concentrations of serum IgG and IgM in patients with pSS decline with time,
      possibly reflecting diminishing inflammatory activity. As in previous studies,
      the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was
      significantly higher than in the reference population.

PMID- 11302869
TI  - Glandular and extraglandular expression of costimulatory molecules in patients
      with Sjogren's syndrome.
AB  - OBJECTIVES: To investigate the expression and regulation of CD80, CD86, and CD28
      costimulatory molecules in sialoadenitis and interstitial nephritis in patients
      with Sjogren's syndrome (SS). METHODS: Expression of CD80, CD86, and CD28
      molecules was studied by immunohistochemical staining of lip biopsy specimens
      obtained from patients who had sialoadenitis associated with SS, and renal biopsy
      specimens obtained from patients who had interstitial nephritis associated with
      SS. To elucidate the mechanism of de novo expression of CD80 and CD86 antigens,
      their induction by cytokines in human salivary duct cell line (HSG) and renal
      cortical epithelial cells (HRCE) by cell enzyme linked immunosorbent assay
      (ELISA) was quantitatively investigated. RESULTS: In patients with severe
      sialoadenitis, CD80 and CD86 were strongly expressed on ductal epithelial cells.
      In contrast, these antigens were not found in the minor salivary glands of normal
      subjects or of patients with mild sialoadenitis. Some infiltrating cells
      expressed CD28. In patients who had interstitial nephritis associated with SS,
      some tubular epithelial cells expressed CD86 but not the CD80 antigen.
      Unstimulated HSG cells did not express CD80 or CD86. Interferon gamma (IFNgamma)
      consistently up regulated levels of CD80 and CD86. In contrast, tumour necrosis
      factor alpha (TNFalpha), interleukin 1beta (IL1beta), IL2, and IL4 had no effect
      on either CD80 or CD86 levels. Unstimulated HRCE did not express CD80 or CD86.
      IFNgamma consistently up regulated CD86 expression. No CD80 expression was found
      on tubular cells. TNFalpha, IL1beta, IL2, and IL4 had no discernible effects.
      CONCLUSIONS: Salivary ductal cells in patients with SS can express CD80 and CD86
      costimulatory molecules in response to IFNgamma. Tubular epithelial cells in
      patients who have interstitial nephritis associated with SS express only CD86
      molecules. In patients with SS, salivary ductal cells and tubular epithelial
      cells may activate infiltrating CD28 positive T lymphocytes by presenting
      antigens to T cells, potentially leading to tissue destruction.

PMID- 11302870
TI  - Polymorphisms of the mannose binding lectin gene in patients with Sjogren's
      syndrome.
AB  - OBJECTIVE: To investigate polymorphisms of both codon 54 allele and promoter
      variants of the mannose binding lectin (MBL) gene in patients with primary
      Sjogren's syndrome (SS). METHODS: Polymorphisms of codon 54 allele and promoter
      variants of the MBL gene in 104 patients with SS and 143 healthy controls were
      determined by polymerase chain reaction-restriction fragment length polymorphism
      and allele specific polymerase chain reaction respectively. RESULTS: The allele
      frequency of the wild type of MBL codon 54 was significantly higher in patients
      with SS than in controls (0.836 v 0.741; p=0.011), and the frequency of the
      homozygous wild type of MBL codon 54 was significantly higher in patients with SS
      than in controls (0.692 v 0.539; p=0.024). On the other hand, the allele
      frequencies of the MBL promoter gene did not differ between patients and controls
      (chi(2)=4.01, df=2, p=0.135). CONCLUSION: The polymorphism of the MBL gene may be
      one of the genetic factors that determines susceptibility to SS.

PMID- 11302871
TI  - Nerve growth factor and neuropeptides circulating levels in systemic sclerosis
      (scleroderma).
AB  - OBJECTIVE: To determine the circulating levels of nerve growth factor (NGF),
      neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) in systemic
      sclerosis (SSc), and to correlate these levels with clinical and laboratory
      features. METHODS: Forty four patients with SSc were evaluated for circulating
      NGF (immunoenzymatic assay), NPY and VIP (radioimmunoassay), anticentromere and
      antitopoisomerase I autoantibodies, lung disease (pulmonary function tests with
      carbon monoxide transfer factor (TLCO), ventilation scintiscan with 99mTc DTPA
      radioaerosol, high resolution computed tomography (HRCT), pulmonary pressure
      (echo colour Doppler)), heart disease (standard and 24 ECG, echocardiography),
      cutaneous involvement (skin score), joint involvement (evidence of tender or
      swollen joints, or both), peripheral nervous system (PNS) involvement
      (electromyography), rheumatoid factor, angiotensin converting enzyme
      (fluorimetric method), von Willebrand factor (ELISA), and erythrocyte
      sedimentation rate (ESR) (Westergren). RESULTS: Circulating NGF levels in SSc
      were significantly increased compared with controls (p<0.00001) and significantly
      higher in the diffuse than in the limited subset of patients (p<0.01). Patients
      with articular disease had significantly higher levels of NGF. A significant
      indirect correlation between NGF levels and TLCO was detected (p<0.01), but no
      correlation was found between NGF and HRCT, DTPA, skin score, PNS involvement and
      angiotensin converting enzyme and von Willebrand factor levels, antitopoisomerase
      or anticentromere antibodies, and ESR. NGF levels increased progressively as the
      disease worsened. Similarly, VIP circulating levels were significantly increased
      in patients with SSc (p<0.001), whereas the increase of NPY levels did not reach
      statistical significance. However, both neuropeptides, following the same trend
      as NGF, increased as the disease worsened (skin score and lung disease).
      CONCLUSIONS: The increase of NGF and VIP in patients with SSc, the former in the
      diffuse subset of the disease, and in patients with prominent articular disease,
      may suggest a link between neurotransmitters and the disease pathogenesis.
      Neuropeptide circulating levels seem to increase only in patients with the most
      severe disease.

PMID- 11302872
TI  - Flow cytometric analysis of gut mucosal lymphocytes supports an impaired Th1
      cytokine profile in spondyloarthropathy.
AB  - OBJECTIVE: To quantify the fraction of gut mucosal lymphocytes expressing the T
      helper type 1 (Th1) cytokines, interferon gamma (IFNgamma) and interleukin (IL)2,
      and the Th2 cytokines, IL4 and IL10, at the single cell level in patients with
      spondyloarthropathy (SpA) in comparison with healthy controls. METHODS: An
      improved extraction protocol was used for the enrichment of intraepithelial
      lymphocytes (IELs) and lamina propria lymphocytes (LPLs) from colonic and ileal
      biopsy specimens obtained from patients with SpA (n=20) and healthy controls
      (n=13). After stimulation with phorbol ester/ionomycin, expression of the
      intracellular cytokines IFNgamma, IL2, IL4, and IL10 was determined in CD3+,
      CD3+CD8+ and CD3+CD8- T cells by flow cytometry. RESULTS: In colonic LPLs, a
      significant decrease in IFNgamma-producing CD3+ cells was observed (p=0.02) in
      patients with SpA. In the CD3+CD8- subset, the proportion of cells producing
      IFNgamma and IL2 was decreased in patients with SpA (p=0.021 and p=0.027
      respectively). In ileal LPLs, the percentage of IL10-producing CD3+CD8- cells was
      significantly increased (p=0.046). CONCLUSION: An impaired Th1 cytokine profile
      is observed in gut mucosal lymphocytes from patients with SpA. This adds to the
      existing evidence that the gut mucosal immune apparatus is involved in the
      pathogenesis of SpA.

PMID- 11302873
TI  - Cofactor dependence and isotype distribution of anticardiolipin antibodies in
      viral infections.
AB  - BACKGROUND: Antibodies to cardiolipin (aCLs) are often detected in patients with
      autoimmune disorders or infectious diseases. OBJECTIVE: To investigate the
      distribution of aCL isotypes and requirement of protein cofactor in viral
      infections in order to establish the importance, if any, of these antibodies in
      these infectious diseases. PATIENTS AND METHODS: The isotype distribution of aCLs
      in the sera from 160 patients with infection caused by HIV-1 (n=40), hepatitis A
      virus (n=40), hepatitis B virus (n=40), or hepatitis C virus (n=40) was studied
      by standardised enzyme linked immunosorbent assay (ELISA) in the presence and
      absence of protein cofactor (mainly beta2-glycoprotein I). Serum samples from
      healthy volunteers and patients with syphilis and antiphospholipid syndrome were
      also included and served as negative and positive control groups respectively.
      RESULTS: The prevalence of one or more aCL isotypes in serum of patients with HIV
      1, hepatitis A virus, hepatitis B virus, or hepatitis C virus infection was 47%,
      92%, 42%, and 17% respectively (principally IgM and/or IgA). Most of these
      antibodies were mainly cofactor independent. CONCLUSIONS: The presence of aCLs in
      viral infections is principally cofactor independent, suggesting that cofactor
      dependence of the aCLs should be assessed to distinguish subjects most likely to
      suffer from clinical symptoms observed in the presence of these antibodies.

PMID- 11302875
TI  - Reversibility of histological and immunohistological abnormalities in sublabial
      salivary gland biopsy specimens following treatment with corticosteroids in
      Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disease characterised by specific
      lesions in exocrine glands, so sublabial minor salivary gland biopsy (SLGB) plays
      an important part in its diagnosis. The extent and composition of the lymphocytic
      infiltrate in SLGB specimens can be considered as target organ specific
      parameters. They are quantified after histological and immunohistological
      examination by a focus score (describing the extent of the infiltrate) and IgA%
      score (describing the composition of the infiltrate), respectively. However,
      little is known about the factors that contribute to the extent and composition
      of the infiltrate and whether these features are reversible as repeated SLGBs are
      rarely performed. A patient with SS is described who underwent SLGBs before and
      after treatment with high dose corticosteroids. After treatment there was not
      only clinical improvement, but also improvement in the histological and
      immunohistological parameters. Although these findings need to be confirmed in
      further studies, this suggests that histopathological changes may be reversible
      in SS. Furthermore, it shows that the potential effects of corticosteroid use
      should be taken into account when interpreting SLGB specimens. When clinical
      changes do parallel histological changes, repeated SLGBs might offer a marker for
      disease activity in patients with SS.

PMID- 11302874
TI  - Impaired catecholaminergic signalling of B lymphocytes in patients with chronic
      rheumatic diseases.
AB  - OBJECTIVE: To investigate further the influence of the autonomic nervous system
      on chronic rheumatic diseases. METHODS: The density and affinity of beta2
      adrenergic receptors (beta2R) on CD19+ lymphocytes in patients with rheumatoid
      arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc),
      as well as intracellular cAMP levels in patients with RA and SLE, were
      determined. Human peripheral blood mononuclear cells were separated from venous
      blood of patients and healthy controls by Ficoll-Hypaque density centrifugation.
      CD19+ lymphocytes were purified by magnetic cell sorting, and beta2R were
      determined by a radioligand binding assay with [125I]iodocyanopindolol.
      Intracellular cAMP levels and beta2R agonist induced cell death were measured by
      a radioimmunoassay and flow cytometry using annexin-V binding, respectively.
      Systemic disease activity of the patients was evaluated using multifactorial
      scoring systems. RESULTS: The density of beta2R on peripheral CD19+ lymphocytes
      was significantly decreased in patients with RA, SLE, and SSc compared with
      healthy controls. In patients with RA and SSc beta2R density was negatively
      correlated with systemic disease activity. Furthermore, although basal
      intracellular cAMP levels were raised in patients with RA and SLE, the increase
      of cAMP upon stimulation of beta2R was significantly reduced in these patients
      compared with control subjects. Preliminary data suggest that beta2R agonist
      induced cell death is diminished in patients with RA exhibiting decreased beta2R
      densities. CONCLUSIONS: The results of this study show a reduction of beta2R
      densities on B lymphocytes mirrored by an impaired intracellular cAMP generation
      in patients with chronic rheumatic diseases, indicating a decreased influence of
      the autonomic nervous system on B cells in these conditions.

PMID- 11302876
TI  - Treatment with cyclosporin switching to hydroxychloroquine in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the therapeutic benefit of cyclosporin A (CSA)
      switching to hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA).
      METHODS: Thirty four patients with RA who displayed residual inflammation and
      disability despite partial responses to prior maximal tolerated doses of
      methotrexate, were included. All were treated with a staged approach using CSA
      for 24 weeks to induce clinical improvement, followed by HCQ for 16 weeks to
      maintain the improvement. Seven ACR core set measures were evaluated every four
      to eight weeks. RESULTS: During a 40 week open trial, 27/34 patients completed
      the study. CSA treatment significantly reduced the tender joints score, swollen
      joints score, visual analogue pain scale, patient's or doctor's global
      assessment, patient's self assessed disability, and C reactive protein. Compared
      with the time of entry into the trial, patients who switched from CSA to HCQ
      still possessed significantly lower levels of most variables, determined at 28,
      32, and 40 weeks. According to the ACR 20% improvement definition, 15/27 (56%)
      patients had improved at 24 weeks after CSA treatment, and 14/27 (52%) remained
      improved at 16 weeks after the change to HCQ. Frequent side effects, such as
      hypertrichosis, gastrointestinal trouble, and hypertension, were noted during CSA
      treatment, but most of these disappeared after switching to HCQ. The mean levels
      of blood pressure and serum creatinine were significantly increased during CSA
      treatment, but returned to normal after changing to HCQ. CONCLUSIONS: The data
      suggest that CSA switching to HCQ treatment may be an effective strategy for
      patients with RA partially responding to methotrexate, particularly those with
      toxicity due to CSA.

PMID- 11302877
TI  - Acute arthritis after intra-articular hyaluronate injection: onset of effusions
      without crystal.
AB  - Side effects of intra-articular hyaluronate injection include aseptic acute
      arthritis, which develops within hours after injection. Based on standard crystal
      analysis, calcium crystal shedding has been postulated to explain this
      complication. However, it is not known whether apatite crystals or low amounts of
      calcium pyrophosphate dihydrate (CPPD) crystals are also involved as to determine
      this requires a complete synovial fluid (SF) analysis. Two cases of such an acute
      arthritis are reported in patients after receiving a second Hylan GF-20 intra
      articular injection. The SF did not contain CPPD, monosodium urate, or calcium
      apatite microcrystals as examined by microscopic analysis (using a compensated
      polarised light microscope) after alizarin red staining. Further studies are
      required to investigate possible direct proinflammatory effects of hyaluronic
      acid degradation products.

PMID- 11302878
TI  - Threefold increased risk of hip fractures with rheumatoid arthritis in Central
      Finland.
AB  - OBJECTIVES: To evaluate the impact of rheumatoid arthritis (RA) on the incidence
      of hip fractures. METHODS: All patients with acute hip fractures admitted to
      Jyvaskyla Central Hospital in 1991-93 (n=517) were selected from the hospital
      discharge register. Medical records of these patients were studied
      retrospectively for RA fulfilling the American Rheumatism Association criteria.
      The prevalence of RA in patients with hip fractures was compared with the
      prevalence rates of RA obtained from the nearby city of Tampere. RESULTS: 29
      (5.6%; 95% CI 3.8 to 8.0) of the patients with hip fracture in Jyvaskyla Central
      Hospital had RA. The age and sex adjusted risk of hip fractures was increased by
      RA (risk ratio 3.26; 95% CI 2.26 to 4.70). CONCLUSIONS: Patients with RA are at
      increased risk of osteoporotic hip fractures.

PMID- 11302879
TI  - Expression of costimulatory molecules on peripheral blood lymphocytes of patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: In systemic lupus erythematosus (SLE) autoantibody production is T
      cell dependent. For a proper T and B cell interaction, signalling of
      costimulatory molecules on these cells is necessary. The expression of
      costimulatory molecules on peripheral blood lymphocytes in patients with SLE in
      conjunction with disease activity was measured to evaluate whether expression of
      costimulatory molecules in SLE is increased. METHODS: Thirteen patients with SLE
      with active disease, 10 patients with inactive disease, and 14 controls entered
      the study. In addition, samples from 10 of the 13 patients with active disease
      could be studied at a moment of inactive disease as well. Isolated peripheral
      blood lymphocytes were stained for the lymphocyte subset markers CD4, CD8, CD19,
      their respective activation markers CD25, HLA-DR, CD38, and the costimulatory
      molecules CD40L, CD28, CD40, CD80, and CD86. Expression was measured by flow
      cytometry. RESULTS: Peripheral blood lymphocytes of patients with SLE showed
      signs of increased activation at the moment of active disease. Almost all CD4+ T
      cells expressed CD28, both in patients and in controls. CD80 expression on CD19+
      B cells was low in both groups and did not correlate with disease activity. In
      contrast, the percentage of CD19+ B cells expressing CD86 was increased in
      patients with SLE even in patients with inactive disease (p=0.04) and correlated
      with the SLEDAI score (p=0.0005) and levels of anti-dsDNA (p=0.006). No changes
      in CD40 or CD40L expression were found in the patients with SLE. CONCLUSION: In
      patients with SLE the expression of CD86 on CD19+ B cells is increased and is
      associated with disease activity, B cell activation, and levels of anti-dsDNA.
      The increased CD86 expression will render (autoreactive) B cells more susceptible
      for T cells. This can facilitate autoantibody production and might be a target
      for immunosuppressive treatments.

PMID- 11302880
TI  - Characteristics of patients with antiphospholipid syndrome with major bleeding
      after oral anticoagulant treatment.
AB  - OBJECTIVE: To study the demographic and clinical characteristics of patients with
      antiphospholipid syndrome (APS) with serious haemorrhagic complications of
      anticoagulant treatment in an attempt to establish risk factors for bleeding.
      METHODS: Patients with APS who were attending our lupus unit and who presented
      with severe bleeding while receiving oral anticoagulation were studied
      retrospectively. Severe bleeding was defined by the need for admission to
      hospital. Demographic data, clinical features, concomitant diseases and drugs,
      warfarin doses, duration of anticoagulation, and International Normalised Ratios
      (INR) at the time of bleeding were collected. RESULTS: Fifteen patients were
      included in the study (12 with systemic lupus erythematosus (SLE) plus APS and 3
      with primary APS). The median age was 41.7 (range 27-66) and the median duration
      of the disease was 12.9 years (range 3-22). Duration of anticoagulation was
      between 10 days and 17 years. The INR at the time of bleeding was under 3 in 4
      patients, between 3 and 4 in 5 patients and above 4 in 6 patients. There were 4
      episodes of subdural haematoma, 4 episodes of renal haematoma (two after renal
      biopsy), 2 episodes of ovarian haemorrhage, 2 episodes of rectal haemorrhage, 1
      episode of menorrhagia, 1 episode of haemarthrosis, and 1 episode of spinal
      haematoma. Concomitant drugs were aspirin in 9 patients, antibiotics in 2
      patients, and azathioprine in 3 patients. In 6 patients hypertension was present
      as a concomitant disease. There were no deaths due to bleeding. Anticoagulant
      treatment was restarted in all patients and 3 of them had a new episode of
      bleeding. CONCLUSION: No relation was established between age, duration of oral
      anticoagulant treatment, and bleeding. Concomitant drugs, mainly aspirin, and
      high blood pressure were present at the time of bleeding in a large number of
      patients.

PMID- 11302881
TI  - HLA-DRB1 genes and patients with late onset rheumatoid arthritis.
AB  - OBJECTIVE: To determine the influence of HLA-DRB*1 genes on susceptibility to and
      severity of rheumatoid arthritis (RA) in patients with late onset compared with
      younger onset disease. METHODS: The clinical, biological, and HLA-DRB1 typing
      characteristics of two groups of patients were studied retrospectively. Group 1
      consisted of 262 patients whose disease onset was before or at the age of 60
      (young onset RA (YORA)). Group 2 included 60 patients whose illness began after
      the age of 60 (elderly onset RA (EORA)). RESULTS: The shared epitope level was
      similarly increased in both groups of patients compared with normal controls
      (195/262 (74%) in group 1 and 43/60 (72%) in group 2 v 645/1609 (40.1%) in
      controls). No differences were noted between the two groups of patients for each
      separate disease related allele. In contrast, when studying all HLA-DRB1*04 RA
      related alleles as a group, these alleles were underrepresented in EORA compared
      with YORA (22/60 (37%) v 135/262 (52%); odds ratio 2.0; 95% confidence interval
      1.0 to 3.3). An inverse trend was seen for HLA-DRB1*01 alleles. There were no
      differences in biological characteristics or extra-articular manifestations
      between the patient groups. The differences noted in radiological evaluation or
      the number of prescribed disease modifying antirheumatic drugs seemed to be
      linked with differences in disease duration. CONCLUSION: HLA-DRB1 RA related
      alleles influence both EORA and YORA. However, HLA-DRB1*04 RA linked alleles are
      not as closely associated with RA in the elderly as they are in younger patients.
      This suggests that the importance of these genes in the susceptibility to RA may
      be lower in elderly patients.

PMID- 11302882
TI  - Reversible posterior leucoencephalopathy syndrome in systemic lupus and
      vasculitis.
AB  - OBJECTIVES: Reversible posterior leucoencephalopathy syndrome (RPLS) may develop
      in patients with renal insufficiency, hypertension, and immunosuppression, and is
      managed by prompt antihypertensive and anticonvulsant treatment. Four patients
      with renal insufficiency and fluid overload associated with Wegener's
      granulomatosis (one patient) and systemic lupus erythematosus (SLE) (three
      patients) are described, whose clinical picture and neuroimaging indicated RPLS.
      CASE REPORTS: All patients had headache, seizures, visual abnormalities, and
      transient motor deficit, and were hypertensive at the onset of the symptoms. Head
      computed tomography (CT) scan and magnetic resonance imaging showed predominantly
      posterior signal abnormalities, which were more conspicuous on T(2) weighted spin
      echo images than on CT scan. All patients had some form of cytotoxic treatment
      shortly before the syndrome developed, and dramatically responded to blood
      pressure control and anticonvulsant treatment. In two patients with SLE, dialysis
      was required for renal insufficiency. DISCUSSION: Follow up neuroimaging studies
      showed almost complete resolution of signal abnormalities, and suggested that
      RPLS was associated with cerebral oedema without concomitant infarction. The
      treatment of hypertension and neurotoxic condition such as uraemia appears of
      primary importance, while immunosuppressive treatment may cause further damage of
      the blood-brain barrier.

PMID- 11302883
TI  - Isolated digital vasculitis in a patient with rheumatoid arthritis: good response
      to tumour necrosis factor alpha blocking treatment.
AB  - Tumour necrosis factor alpha (TNFalpha) blocking agents are among the most
      promising new treatments for rheumatoid arthritis (RA). However, no data exist
      about the effect of these agents on extra-articular manifestations of RA. A
      patient is described with small vessel vasculitis that repeatedly responded well
      to treatment with the soluble p55 TNFalpha receptor fusion protein Ro 45-2081
      (lenercept).

PMID- 11302884
TI  - Resources, Down's syndrome, and cardiac surgery.

PMID- 11302885
TI  - Synchronous chemoradiation for squamous carcinomas.

PMID- 11302886
TI  - HPV testing for clarifying borderline cervical smear results.

PMID- 11302887
TI  - Any casualties in the clash of randomised and observational evidence?

PMID- 11302888
TI  - Public health concerns grow over foot and mouth outbreak.

PMID- 11302889
TI  - Antibiotics database launched.

PMID- 11302890
TI  - Atypical antipsychotics in the treatment of schizophrenia. Pragmatic
      considerations are important when considering which drug to prescribe.

PMID- 11302891
TI  - Screensaver harnesses computer power for cancer research.

PMID- 11302895
TI  - Tuberculosis outbreak hits the UK.

PMID- 11302897
TI  - Dutch GP convicted after concealing rape sentence.

PMID- 11302898
TI  - Changes in blood pressure among students attending Glasgow University between
      1948 and 1968: analyses of cross sectional surveys.
AB  - OBJECTIVES: To examine the changes in blood pressure over time in a cohort of
      young adults attending university between 1948 and 1968. DESIGN: Cross sectional
      study. SETTING: Glasgow University. PARTICIPANTS: 12 414 students aged 16-25
      years-9248 men (mean age 19.9 years) and 3164 women (19.2 years)-who participated
      in health screening on entering university between 1948 and 1968. MAIN OUTCOME
      MEASURES: Systolic and diastolic blood pressure. RESULTS: In male students mean
      systolic blood pressure adjusted for age decreased from 134.5 (95% confidence
      interval 133.8 to 135.2) mm Hg in those born before 1929 to 125.7 (125.0 to
      126.3) mm Hg in those born after 1945, and diastolic blood pressure dropped from
      80.3 (79.8 to 80.8) mm Hg to 74.7 (74.2 to 75.1) mm Hg. For female students the
      corresponding declines were from 129.0 (127.5 to 130.5) mm Hg to 120.6 (119.8 to
      121.4) mm Hg and from 79.7 (78.7 to 80.6) mm Hg to 77.0 (76.5 to 77.5) mm Hg.
      Adjustment for potential confounding factors made little difference to these
      findings. The proportion of students with hypertension declined substantially in
      both sexes. CONCLUSIONS: Substantial declines in systolic and diastolic blood
      pressure over time were occurring up to 50 years ago in young adults who were not
      taking antihypertensive medication. Since blood pressure tracks into adult life,
      the results of the cross sectional comparisons suggest that factors acting in
      early life may be important in determining population risk of cardiovascular
      disease. Changes in such factors may have made important contributions to the
      decline in rates of cardiovascular diseases, particularly stroke, seen in
      developed countries during the past century.

PMID- 11302899
TI  - Birth weight and childhood onset type 1 diabetes: population based cohort study.
AB  - OBJECTIVE: To assess the associations between birth weight or gestational age and
      risk of type 1 diabetes. DESIGN: Population based cohort study by record linkage
      of the medical birth registry and the National Childhood Diabetes Registry.
      SETTING: Two national registries in Norway. PARTICIPANTS: All live births in
      Norway between 1974 and 1998 (1 382 602 individuals) contributed a maximum of 15
      years of observation, a total of 8 184 994 person years of observation in the
      period 1989 to 1998. 1824 children with type 1 diabetes were diagnosed between
      1989 and 1998. MAIN OUTCOME MEASURES: Estimates of rate ratios with 95%
      confidence intervals for type 1 diabetes from Poisson regression analyses.
      RESULTS: The incidence rate of type 1 diabetes increased almost linearly with
      birth weight. The rate ratio for children with birth weights 4500 g or more
      compared with those with birth weights less than 2000 g was 2.21 (95% confidence
      interval 1.24 to 3.94), test for trend P=0.0001. There was no significant
      association between gestational age and type 1 diabetes. The results persisted
      after adjustment for maternal diabetes and other potential confounders.
      CONCLUSION: There is a relatively weak but significant association between birth
      weight and increased risk of type 1 diabetes consistent over a wide range of
      birth weights.

PMID- 11302900
TI  - Human papillomavirus testing and the management of women with mildly abnormal
      cervical smears: an observational study.

PMID- 11302901
TI  - Do obstetric complications explain high caesarean section rates among women over
      30? A retrospective analysis.

PMID- 11302902
TI  - Take home naloxone and the prevention of deaths from opiate overdose: two pilot
      schemes.

PMID- 11302903
TI  - Surgeons' attitudes to intraoperative death: questionnaire survey.

PMID- 11302904
TI  - Drug points: Benign intracranial hypertension secondary to nasal fluticasone
      propionate.

PMID- 11302905
TI  - Randomised controlled trial of Helicobacter pylori testing and endoscopy for
      dyspepsia in primary care.
AB  - OBJECTIVE: To determine the cost effectiveness of a strategy of near patient
      Helicobacter pylori testing and endoscopy for managing dyspepsia. DESIGN:
      Randomised controlled trial. SETTING: 31 UK primary care centres. PARTICIPANTS:
      478 patients under 50 years old presenting with dyspepsia of longer than four
      weeks duration. INTERVENTIONS: Near patient testing for H pylori and open access
      endoscopy for patients with positive results. Control patients received acid
      suppressing drugs or specialist referral at general practitioner's discretion.
      MAIN OUTCOME MEASURES: Cost effectiveness based on improvement in symptoms and
      use of resources at 12 months; quality of life. RESULTS: 40% of the study group
      tested positive for H pylori. 45% of study patients had endoscopy compared with
      25% of controls. More peptic ulcers were diagnosed in the study group (7.4% v
      2.1%, P=0.011). Paired comparison of symptom scores and quality of life showed
      that all patients improved over time with no difference between study and control
      groups. No significant differences were observed in rates of prescribing,
      consultation, or referral. Costs were higher in the study group ( 367.85 pound
      sterling v 253.16 pound sterling per patient). CONCLUSIONS: The test and
      endoscopy strategy increases endoscopy rates over usual practice in primary care.
      The additional cost is not offset by benefits in symptom relief or quality of
      life.

PMID- 11302907
TI  - Recent Advances: Orthopaedics.

PMID- 11302908
TI  - Lesson of the week: "High" ear piercing and the rising incidence of
      perichondritis of the pinna.

PMID- 11302909
TI  - Evidence based treatment of hypertension. Measurement of blood pressure: an
      evidence based review.

PMID- 11302910
TI  - ABC of hypertension: The pathophysiology of hypertension.

PMID- 11302911
TI  - Reducing maternal mortality in the developing world: sector-wide approaches may
      be the key.

PMID- 11302912
TI  - Call for a new approach to the process of clinical trials and drug registration.

PMID- 11302913
TI  - Psychological debriefing. Qualitative research may be more appropriate.

PMID- 11302914
TI  - Atypical antipsychotics in the treatment of schizophrenia. Paper underrates
      patients' experience of extrapyramidal symptoms.

PMID- 11302915
TI  - Atypical antipsychotics in the treatment of schizophrenia. "Informed relationship
      between doctor and patient" does not exist in many parts of the world.

PMID- 11302916
TI  - Atypical antipsychotics in the treatment of schizophrenia. Paper corrupts concept
      of evidence based medicine.

PMID- 11302917
TI  - Atypical antipsychotics in the treatment of schizophrenia. Validity of dropout
      rates as proxy measure of tolerability is unknown.

PMID- 11302918
TI  - Psychological debriefing. Providing good clinical care means listening to women's
      concerns.

PMID- 11302919
TI  - Atypical antipsychotics in the treatment of schizophrenia. Users' views are
      important.

PMID- 11302920
TI  - Psychological debriefing. Research methodology was inadequate.

PMID- 11302921
TI  - Atypical antipsychotics in the treatment of schizophrenia. Cost is a crucial
      issue.

PMID- 11302922
TI  - Hands off technique has many benefits for breastfeeding mothers.

PMID- 11302923
TI  - International funding for AIDS care in poor countries should be increased,.

PMID- 11302924
TI  - Atypical antipsychotics in the treatment of schizophrenia. Users' experiences of
      treatments must be considered.

PMID- 11302925
TI  - Cyp3A regulation: from pharmacology to nuclear receptors.
AB  - Among the human liver cytochrome P450s (P450s), a family of microsomal
      hemoproteins responsible for catalyzing the oxidative metabolism of clinically
      used drugs and environmental chemicals, attention has been focused on CYP3A, a
      form that is the most abundant and is inducible by many of its substrates. From
      early pharmacological studies that demonstrated induction of CYP3A by
      glucocorticoids and, paradoxically, by antiglucocorticoids, the existence of a
      nonclassical glucocorticoid receptor mechanism was inferred and prompted research
      that culminated in the identification of a unique member of the nuclear receptor
      family, the pregnane X receptor (PXR; NR1I2). It has become increasingly evident
      that PXR as well as other nuclear receptors mediate CYP3A induction in a unique
      and complex manner including inducibility by structurally diverse compounds and
      striking interspecies differences in induction profiles. Future understanding of
      the role of nuclear receptors in regulating expression of CYP3A and other genes
      of the P450 family offers an exciting promise of further defining the physiologic
      function and interindividual differences of CYP3A in health and disease.

PMID- 11302927
TI  - Multidrug resistance p-glycoprotein 2 is essential for the biliary excretion of
      indocyanine green.
AB  - Multidrug resistance P-glycoprotein 2 (Mdr2) is a phospholipid translocator in
      the canalicular membrane that is essential for the formation of biliary
      phospholipid vesicles and mixed lipid/bile salt micelles. Incorporation into
      biliary vesicles and micelles is thought to contribute to the hepatobiliary
      excretion of certain hydrophobic organic anions, such as indocyanine green (ICG).
      The present studies characterized the biliary excretion of two hydrophobic
      organic anions, ICG and estradiol-17beta(beta-D-glucuronide) (E(2)17G), in the
      single-pass isolated perfused liver and the biliary excretion of glutathione
      (GSH) in vivo in wild-type and Mdr2-/- female mice. The biliary excretion of ICG
      (0.4 micromol) was reduced by 90%, while the biliary excretion of total GSH was
      decreased by 65% in Mdr2-/- mice relative to wild-type mice. In contrast, the
      biliary excretion of E(2)17G (0.1 micromol) was increased by 30% in Mdr2-/- mice.
      These data indicate that the absence of Mdr2 differentially influences the
      biliary excretion of these organic anions and suggest that phospholipid vesicles
      and mixed micelles in bile are essential for the biliary excretion of ICG.

PMID- 11302926
TI  - Molecular regulation of genes encoding xenobiotic-metabolizing enzymes:
      mechanisms involving endogenous factors.
AB  - It is widely recognized that xenobiotic-metabolizing enzymes play a fundamental
      role in the basic processes of carcinogenesis and toxicity on one hand, and
      chemoprevention and drug efficacy on the other. Realization that different
      factors can profoundly affect the expression of these enzymes at the genome level
      has resulted in an enhanced appreciation of the importance these genes play in
      our modern industrialized age. There continues to be rapid proliferation of
      studies addressing the molecular regulation of these genes. The discovery of
      common signal transduction pathways and transcription factors that dictate tissue
      and developmental-specific expression, as well as variation in expression within
      a given tissue, suggest that there may be significant interaction among these
      various regulatory systems. This report is a summary of a symposium that was part
      of the Structure, Function and Regulation of Cytochromes P450 and Xenobiotic
      Metabolizing Enzymes satellite meeting of the 2000 joint meeting of the American
      Society for Biochemistry and Molecular Biology, the American Society for
      Pharmacology and Experimental Therapeutics, the French Pharmacological Society,
      and the Pharmacological Society of Canada held in Boston, Massachusetts. This
      symposium brought together several speakers who addressed specific receptor
      mediated signal transduction pathways involved in the regulation of xenobiotic
      metabolizing enzymes, as well as other molecular mechanisms whereby endogenous
      factors are involved in controlling tissue- and developmental-specific
      expression.

PMID- 11302928
TI  - In vitro metabolism of the COX-2 inhibitor DFU, including a novel glutathione
      adduct rearomatization.
AB  - The metabolic profile of DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4
      methylsulphonyl)phenyl-2(5H)-furanone], a potent and selective COX-2 inhibitor,
      was characterized using in vitro microsomal and hepatocyte incubations. A single
      product, corresponding to p-hydroxylation, p-OH-DFU [(5,5-dimethyl-3-(3-fluoro-4
      hydroxyphenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone)], was produced in rat
      microsomal incubations of DFU. In contrast, three metabolites were produced in
      incubations using suspensions of freshly isolated rat hepatocytes. Microsomal
      production of the p-O-glucuronide metabolite of DFU from synthetic p-OH-DFU was
      shown to have chromatographic and mass spectrometric properties identical to the
      earliest eluting hepatocyte metabolite (M1). The molecular weights of the other
      two hepatocyte metabolites were readily obtained using capillary high-performance
      liquid chromatography continuous-flow liquid secondary ion mass spectrometry
      (HPLC/CF-LSIMS); however, the elemental composition of these metabolites was not.
      Unlike typical metabolic products, which produce readily identified increments in
      molecular weight, metabolites M2 and M3 produced molecular ions in positive- and
      negative-ion CF-LSIMS that were consistent with oxidation of DFU (+16 Da),
      followed by addition of glutathione (+306 Da) and subsequent loss of 20 and 18
      Da, respectively. Capillary HPLC/high-resolution CF-LSIMS was used to generate
      accurate mass data for M2 and M3 that provided evidence that the losses of 20 and
      18 Da, respectively, corresponded to a rearomatization through loss of HF or
      H(2)O. Isolation and NMR characterization provided the definitive structural
      proof for these metabolites. Overall, the metabolism of DFU in rat hepatocytes is
      proposed to proceed through an epoxide intermediate, which then either rearranges
      to the p-OH-DFU and is conjugated with glucuronic acid, or is trapped with
      glutathione, followed by rearomatization with loss of HF (M2) or H(2)O (M3).

PMID- 11302929
TI  - Accumulation of nicotine and its metabolites in rat brain after intermittent or
      continuous peripheral administration of [2'-(14)C]nicotine.
AB  - Concentrations of nicotine, cotinine, and nornicotine in brain and blood
      following both intermittent and continuous administration of [2'-(14)C]nicotine
      to rats were determined to assess nicotine metabolite accumulation in brain
      following repeated nicotine administration. For intermittent studies, rats were
      administered s.c. 1 to 10 doses of nicotine (0.3 mg/kg, 15 or 25 microCi of [2'
      (14)C]nicotine; 30-min interinjection interval). For continuous administration
      studies, rats were implanted s.c. with an osmotic minipump delivering nicotine
      (0.8 mg/kg/day, 25 or 50 microCi of [2'-(14)C]nicotine for 1-21 days). Whole
      brain and trunk blood was collected. The concentration of [2'-(14)C]nicotine and
      its metabolites was determined via high-pressure liquid radiochromatography.
      Brain concentrations of nicotine, cotinine, and nornicotine increased 2-, 12-,
      and 9-fold, respectively, following 10 injections, reaching a plateau following
      the fifth injection. Brain blood ratios indicate an enhanced preferential
      distribution of nornicotine to brain with increasing numbers of injections.
      Across the 21-day period of continuous infusion, blood nicotine and nornicotine
      concentrations remained relatively constant, whereas concentrations in brain
      increased approximately 4-fold. Generally, cotinine concentrations in brain and
      blood did not change across the infusion period. Brain/blood ratios indicate an
      increase in nicotine distribution into brain across days of nicotine infusion.
      Results demonstrate that both nicotine and its metabolites accumulate in brain
      following repeated nicotine administration, and indicate that brain nicotine
      concentration can not be extrapolated from plasma cotinine or nicotine
      concentrations. Thus, nornicotine accumulation following repeated nicotine
      administration suggests that this metabolite plays a contributory role in the
      neuropharmacological effects of nicotine.

PMID- 11302930
TI  - 13-hydroxy- and 13-oxooctadecadienoic acids: novel substrates for human UDP
      glucuronosyltransferases.
AB  - Although there are numerous studies of glucuronidation of endogenous compounds,
      information on the glucuronidation of fatty acids is lacking. In the present
      studies, both linoleic acid (LA) and its biologically active oxidized
      derivatives, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic
      acid (13-OXO), have been shown to be effective substrates for human liver UDP
      glucuronosyltransferases (UGT) and recombinant UGT2B7. LA (carboxyl glucuronide)
      and 13-OXO (carboxyl glucuronide, unproven) were actively glucuronidated by human
      liver microsomes (HLM) and human recombinant UGT2B7 with similar activities, in
      the range of 2 nmol/mg. min. The hydroxyl derivative of LA, 13-HODE, was
      glucuronidated at both the hydroxyl and carboxyl functions with carboxyl
      glucuronidation predominating (ratio of COOH/OH, 2:1). For all substrates, the
      K(m) for formation of the carboxyl-linked glucuronide was in the range of 100 to
      200 microM while that for the hydroxyl-linked glucuronide was somewhat lower
      (>100 microM). This is the first demonstration of glucuronidation of LA and its
      oxidized derivatives, 13-HODE and 13-OXO, by HLM and recombinant UGT2B7.

PMID- 11302931
TI  - Metoprolol-paroxetine interaction in human liver microsomes: stereoselective
      aspects and prediction of the in vivo interaction.
AB  - This study in human liver microsomes was undertaken to establish whether
      paroxetine stereoselectively inhibits the oxidative metabolism of metoprolol in
      vitro, and whether the in vivo observed magnitude of the paroxetine-metoprolol
      interaction was predictable from these in vitro data. Two distinct approaches
      were used: inhibitory effect of paroxetine on 1) the formation of alpha
      hydroxymetoprolol and O-desmethylmetoprolol from the individual metoprolol
      enantiomers and 2) on the depletion of the enantiomers from the incubation
      mixture. Nonspecific binding of both metoprolol and paroxetine to human liver
      microsomes was also investigated. Whereas metoprolol displayed negligible
      binding, paroxetine was extensively bound to microsomal proteins. This was taken
      into account in order to obtain unbiased K(i) values and unbound concentrations
      of paroxetine. In the substrate depletion experiments, the intrinsic clearance
      (CL(int)) of (R)-metoprolol was larger than that of (S)-metoprolol. Paroxetine
      caused a concentration-dependent decrease in CL(int) of both enantiomers and
      abolished the stereoselectivity. In the metabolite formation experiments
      paroxetine did not stereoselectively affect alpha-hydroxylation, but
      preferentially inhibited the O-demethylation of the (R)-enantiomer versus the (S)
      enantiomer. The use of unbound paroxetine concentrations in the two in vitro
      methods yielded comparable predicted increases in area under the curve (1.7-1.9
      and 2.2-2.5 for (S)- and (R)-metoprolol, respectively) but underestimated the in
      vivo observed changes of about 7- and 10-fold, respectively. In conclusion, this
      study showed that paroxetine abolishes the stereoselective metabolism of
      metoprolol due to a stereoselective inhibition of the O-demethylation toward (R)
      metoprolol. Furthermore, the extent of the in vivo metoprolol-paroxetine
      interaction was substantially underestimated by either one of the two in vitro
      approaches used when a competitive mechanism was assumed.

PMID- 11302932
TI  - Dose-dependent pharmacokinetics and metabolism of valproic acid in newborn lambs
      and adult sheep.
AB  - Dose-dependent pharmacokinetics and metabolism of valproic acid (VPA) were
      studied in newborn and adult sheep to assess age-related differences in plasma
      protein binding and metabolic elimination. Newborn lambs received either a 10- (n
      = 8), 50- (n = 5), 100- (n = 4), or 250-mg/kg (n = 4) VPA i.v. bolus. Individual
      adult sheep (n = 5) received all four doses in a random order with an appropriate
      washout period between experiments. Unbound or metabolic clearance of VPA was
      significantly higher in adult sheep at the two lower doses when compared with
      lambs, and similar to the lambs at the two higher doses. Plasma protein binding
      was nonlinear at all doses. Estimates of binding capacity (B(max1)) at the
      saturable site were higher in adults (91.8 microg/ml) when compared with lambs
      (44.9 microg/ml), whereas the opposite trend was observed for binding affinity
      [K(d1) = 9.6 microg/ml (adult) versus 3.2 microg/ml (lambs)]. Characterization of
      developmental differences in overall VPA metabolic elimination involved fitting
      of unbound VPA plasma concentration data to a two-compartment model with
      Michaelis-Menten elimination. This resulted in similar in vivo estimates of
      apparent V(max) [445.0 microg/min/kg (adult) versus 429.9 microg/min/kg (lambs)].
      However, apparent K(m) estimates appeared to be higher in lambs [30.0 microg/ml
      (adult) versus 69.6 microg/ml (lambs)]. Similar findings were obtained from in
      vivo estimates of V(max) and K(m) for VPA glucuronidation obtained from VPA
      glucuronide metabolite urinary excretion data. Thus, it appears that age-related
      differences in metabolic clearance may be related to differences in the apparent
      in vivo K(m) as opposed to V(max) of VPA glucuronidation.

PMID- 11302933
TI  - Spermidine/spermine n(1)-acetyltransferase catalyzes amantadine acetylation.
AB  - Amantadine acetylation was demonstrated to occur both in vivo and in vitro using
      transgenic male mice overexpressing spermidine/spermine N(1)-acetyltransferase
      (SSAT). We previously reported that neither NAT1 nor NAT2 was responsible for
      catalyzing acetylation of the primary amine group of amantadine. We hypothesized
      that the inducible polyamine-catabolizing enzyme, SSAT, was an alternate pathway
      for acetylating amantadine. Transgenic mice injected s.c. with 3 mg/kg amantadine
      excreted 4.5 +/- 1% (mean +/- S.E.) of the administered dose as acetylamantadine
      in 24-h urine samples while, by contrast, nontransgenic control mice failed to
      excrete any detectable acetylamantadine in their urine. In vitro studies with the
      cytosolic liver fraction from transgenic mice as the source of SSAT demonstrated
      spermidine acetylation catalytic activity with an apparent K(m) = 267 +/- 46
      microM and V(max) = 0.009 +/- 0.002 nmol/min/mg of protein. Amantadine
      competitively inhibited spermidine acetylation with an apparent K(i) = 738 +/-
      157 microM. Incubation of amantadine, SSAT, and an acetyl CoA-regenerating system
      produced modest amounts of acetylamantadine. The NAT2 substrate, sulfamethazine,
      inhibited spermidine acetylation with a calculated K(i) = 3.5 mM, suggesting that
      SSAT may be an alternate pathway for acetylation of NAT2 substrates. The NAT1
      substrate, p-aminobenzoic acid, had no inhibitory effect. These results provide
      evidence that amantadine can be acetylated by SSAT and may be a specific drug
      substrate for this enzyme. Further investigation of the role of SSAT as a
      potential drug-metabolizing pathway is warranted.

PMID- 11302934
TI  - Biodistribution of 4-[(14)C]cholesterol-AmBisome following a single intravenous
      administration to rats.
AB  - A biodistribution study of 4-[(14)C]cholesterol-AmBisome; a unilamellar liposomal
      preparation of amphotericin B was conducted to support a radiolabeled human
      study. The radioactive plasma concentration profile (as measured in microg-Eq/ml
      of cholesterol) was best fit to a sum of three exponentials that yielded alpha-,
      beta-, and gamma-half-life estimates of 3.0 +/- 0.3, 11.8 +/- 3.7, and 113.4 +/-
      32.4 h, respectively. Clearance and the steady state volume of distribution were
      4.9 +/- 0.2 ml/h/kg and 341 ml/kg. Recovery data collected up through 96 h
      demonstrated mass balance and indicated that although the elimination profile in
      both urine and feces were incomplete, the dominant route of elimination (<2% in
      urine versus 33% in feces) was feces, presumably via biliary excretion of intact
      liposome and/or cholesterol. The liver, spleen, and lungs, organs of the
      reticuloendothelial system known for their rapid uptake of liposomes, presented
      with the highest levels of radioactivity. Levels in the kidney were 15% of that
      found in the liver and lungs.

PMID- 11302935
TI  - Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7.
AB  - Epirubicin is one of the most active agents for breast cancer. The formation of
      epirubicin glucuronide by liver UDP-glucuronosyltransferase (UGT) is its main
      inactivating pathway. This study aimed to investigate epirubicin glucuronidation
      in human liver microsomes, to identify the specific UGT isoform for this
      reaction, and to correlate epirubicin glucuronidation with other UGT substrates.
      Microsomes from human livers were used. UGTs specifically expressed in cellular
      systems, as well as two UGT2B7 variants, were screened for epirubicin
      glucuronidation. Epirubicin, morphine, and SN-38 glucuronides were measured by
      high-pressure liquid chromatography. The mean +/- S.D. formation rate of
      epirubicin glucuronide in human liver microsomes (n = 47) was 138 +/- 37
      pmol/min/mg (coefficient of variation, 24%). This phenotype was normally
      distributed. We screened commercially available UGT1A1, UGT1A3, UGT1A4, UGT1A6,
      UGT1A9, UGT2B7, and UGT2B15 for epirubicin glucuronidation. Only UGT2B7 converted
      epirubicin to its glucuronide. No differences in epirubicin glucuronidation were
      found in HK293 cells expressing the two UGT2B7 variants at position 268.
      Catalytic efficiency (V(max)/K(m)) of epirubicin glucuronidation was 1.4
      microl/min/mg, a value higher than that observed for morphine, a substrate of
      UGT2B7. Formation of epirubicin glucuronide was significantly related to that of
      morphine-3-glucuronide (r = 0.76, p < 0.001) and morphine-6-glucuronide (r =
      0.73, p < 0.001). No correlation was found with SN-38, a substrate of UGT1A1 (r =
      0.04). UGT2B7 is the major human UGT catalyzing epirubicin glucuronidation, and
      UGT2B7 is the candidate gene for this phenotype. The reported tyrosine to
      histidine polymorphism in UGT2B7 does not alter the formation rate of epirubicin
      glucuronide, and undiscovered genetic polymorphisms in UGT2B7 might change the
      metabolic fate of this important anticancer agent.

PMID- 11302936
TI  - Characterization of expressed full-length and truncated FMO2 from rhesus monkey.
AB  - Flavin-containing monooxygenase (FMO) metabolizes a wide variety of nitrogen,
      sulfur, and phosphorous-containing xenobiotics. FMO2 is highly expressed in the
      lung of most mammals examined, but the protein has only recently been detected in
      humans, presumably due to a premature stop codon at AA472 in most individuals. In
      this study, full-length (mFMO2-535) and 3'-truncated (mFMO2-471) monkey FMO2
      protein, produced by cDNA-mediated baculovirus expression, were characterized and
      compared with baculovirus-expressed rabbit FMO2 (rFMO2-535). Although baculovirus
      expressed mFMO2-535 had properties similar to FMO in monkey lung microsomes and
      had catalytic properties similar to rFMO2-535, the expressed proteins differed in
      a number of properties in S-oxidation assays. Both enzymes had the same pH optima
      (pH 9.5); however, mFMO2-535 quickly lost activity at higher pH values whereas
      rFMO2-535 retained the majority of its activity. Also, mFMO2-535 was
      significantly less stable at elevated temperatures and in the presence of cholic
      acid but had greater activity in the presence of magnesium. mFMO2-535 had higher
      apparent K(m) and V(max)/K(m) values than rFMO2-535 did in N-oxygenation assays.
      mFMO2-471 was correctly targeted to the membrane fraction, but N- and S
      oxygenation was not detected. Since the AA sequence identity of mFMO2 and human
      FMO2 is 97%, our results with mFMO2-535 suggest that individuals carrying the
      allele encoding full-length FMO2 are likely to have in vivo FMO2 activity. Such
      activity could result in marked differences in the metabolism, efficacy, and/or
      toxicity of drugs and xenobiotics for which lung is a portal of entry or target
      organ.

PMID- 11302937
TI  - Metabolism of sulfinpyrazone sulfide and sulfinpyrazone by human liver microsomes
      and cDNA-expressed cytochrome P450s.
AB  - Human liver microsomes catalyze the oxidation of sulfinpyrazone sulfide (SPZS) to
      a variable mixture of sulfinpyrazone (SPZ) enantiomers and two minor phenolic
      metabolites. In one, the thiophenyl ring is hydroxylated, whereas in the second
      an N-phenyl ring is hydroxylated. SPZ is further oxidized to sulfinpyrazone
      sulfone (SPZO) and a minor polar metabolite that also has an N-phenyl ring
      hydroxylated. Determination of the metabolism of SPZ and SPZS under modified
      incubation conditions of prior heat treatment, higher pH, and the presence of
      detergent indicated that the formation of SPZ was cytochrome P450 (P450)- but not
      flavin monooxygenase-dependent. Specific P450 inhibitors (sulfaphenazole,
      quinidine sulfate, coumarin, diethyldithiocarbamic acid, troleandomycin, and
      furafylline) and specific cDNA-expressed P450s were used to identify the major
      isoforms responsible for the oxidation of SPZS to SPZ and SPZ to SPZO. Both P450
      2C9 and P450 3A4 were responsible for the oxidation of SPZS to SPZ, whereas P450
      3A4 alone catalyzed the further oxidation of SPZ to SPZO. SPZS was found to be
      metabolized by P450 2C9 to SPZ with a high degree of enantiomeric selectivity
      (9:1) and a K(m) comparable with its previously determined K(i) for inhibition of
      the P450 2C9-dependent 7-hydroxylation of (S)-warfarin (WARF). In contrast, the
      P450 3A4-catalyzed oxidation of SPZS to SPZ proceeded with the same
      enantioselectivity but to a much lesser degree (58:42). These results provide
      evidence that the metabolism of both (S)-WARF and SPZS is mediated by a common
      enzyme, P450 2C9, which is central to understanding the WARF-SPZ interaction and
      SPZS-mediated drug interactions in general.

PMID- 11302938
TI  - An assessment of human liver-derived in vitro systems to predict the in vivo
      metabolism and clearance of almokalant.
AB  - The ability of various human derived in vitro systems to predict various aspects
      of the in vivo metabolism and kinetics of almokalant have been investigated in a
      multicenter collaborative study. Although almokalant has been withdrawn from
      further clinical development, its metabolic and pharmacokinetic properties have
      been well characterized. Studies with precision-cut liver slices, primary
      hepatocyte cultures, and hepatic microsomal fractions fortified with UDP
      glucuronic acid all suggested that almokalant is mainly glucuronidated to the
      stereoisomers M18a and M18b, which is in good agreement with the results in vivo.
      Both in vivo and in vitro studies indicate that the formation of M18b dominates
      over that of M18a, although the difference is more pronounced with the in vitro
      systems. Molecular modeling, cDNA-expressed enzyme analysis, correlation
      analysis, and inhibition studies did not clearly indicate which P450 enzymes
      catalyze the oxidative pathways, which may indicate a problem in identifying
      responsible enzymes for minor metabolic routes by in vitro methods. All of the in
      vitro systems underpredicted the metabolic clearance of almokalant, which has
      previously been reported to be a general problem for drugs that are cleared by
      P450-dependent metabolism. Although few studies on in vivo prediction of
      primarily glucuronidated drugs have appeared, in vitro models may consistently
      underpredict in vivo metabolic clearance. We conclude that in vitro systems,
      which monitor phase II metabolism, would be beneficial for prediction of the in
      vivo metabolism, although all of the candidate liver-derived systems studied
      here, within their intrinsic limitations, provided useful information for
      predicting metabolic routes and rates.

PMID- 11302939
TI  - Intestinal bioavailability and biotransformation of 3-hydroxybenzo(a)pyrene in an
      isolated perfused preparation from channel catfish, Ictalurus punctatus.
AB  - The intestinal bioavailability and biotransformation of 3-hydroxybenzo(a)pyrene,
      a major metabolite of benzo(a)pyrene in many animal species, was investigated in
      an in situ isolated intestinal preparation from the channel catfish, and in vitro
      with preparations of catfish intestine and blood. 3-Hydroxybenzo(a)pyrene was a
      good substrate for adenosine 3'-phosphate 5'-phosphosulfate (PAPS)
      sulfotransferase and UDP-glucuronosyltransferase in cytosol or microsomes
      prepared from intestinal mucosa. The benzo(a)pyrene-3-glucuronide and 3-sulfate
      conjugates were only very slowly hydrolyzed by intestinal beta-glucuronidase and
      sulfatase. The K(m) values for PAPS-sulfotransferase and UDP
      glucuronosyltransferase were 0.4 and 1 microM, respectively, and V(max) were 1.61
      +/- 1.08 nmol benzo(a)pyrene-3-sulfate/min/mg of cytosolic protein and 1.08 +/-
      0.54 nmol benzo(a)pyrene-3-glucuronide/min/mg of microsomal protein. Hydrolytic
      enzyme activities were three orders of magnitude slower. In the in situ
      intestinal preparation, [(3)H]3-hydroxybenzo(a)pyrene was readily metabolized to
      the glucuronide and sulfate conjugates. After 1 h of incubation of 2 or 20 microM
      [(3)H]3-hydroxybenzo(a)pyrene in the in situ preparation, the luminal contents
      contained 3-hydroxybenzo(a)pyrene, benzo(a)pyrene-3,6-dione, benzo(a)pyrene-3
      sulfate, and benzo(a)pyrene-3-glucuronide. Mucosal samples contained these
      components, as well as some unextractable material. The blood contained mainly
      benzo(a)pyrene-3-sulfate and an as yet unidentified metabolite of 3
      hydroxybenzo(a)pyrene bound to hemoglobin. Some, but not all, blood samples
      contained small amounts of 3-hydroxybenzo(a)pyrene, benzo(a)pyrene-3-glucuronide,
      and benzo(a)pyrene-3,6-dione. These studies demonstrate the rapid phase 2
      conjugation of a phenolic benzo(a)pyrene metabolite in intestinal mucosa, and the
      transfer of the phase 2 sulfate and glucuronide conjugates to blood.

PMID- 11302941
TI  - Involvement of semicarbazide-sensitive amine oxidase in tresperimus metabolism in
      human and in rat.
AB  - The metabolism of tresperimus, a new immunosuppressive agent, was investigated in
      vivo and in vitro in rat and in human. Two metabolic pathways were identified at
      each side of the molecule with two deamination reactions on the spermidine moiety
      and hydrolysis of the amide bond leading to the liberation of
      guanidinohexylamine. As the major metabolic pathway of the drug seemed to be the
      oxidative deamination, the capacity of different amine oxidases to metabolize
      tresperimus was then tested using in vivo experiments in rat and in vitro studies
      in rat and human plasma. The increase of tresperimus plasma levels induced by the
      administration of hydralazine, an irreversible in vivo inhibitor of semicarbazide
      sensitive amine oxidase (SSAO), reflected the major involvement of this enzyme in
      tresperimus metabolism. This result was confirmed in vitro in rat and human
      plasma by the use of semicarbazide, a specific SSAO inhibitor. As opposed to rat
      plasma, human plasma may be an interesting in vitro model to study the metabolism
      of a drug extensively metabolized by SSAO such as tresperimus. Indeed, SSAO
      activity was significantly higher in human plasma than in rat plasma. The second
      metabolic pathway of the drug, which only occurred in rat plasma, appeared thus
      as the major route of tresperimus metabolism in this biological matrix.

PMID- 11302940
TI  - Liquid chromatography-mass spectrometry and liquid chromatography-NMR
      characterization of in vitro metabolites of a potent and irreversible
      peptidomimetic inhibitor of rhinovirus 3C protease.
AB  - In vitro metabolism of AG7088 [trans-(4S,2'R,5'S,3"'S)-4-[2'-4-(4-fluorobenzyl)
      6'-methyl-5'-[(5"-methylisoxazole-3"-carbonylamino]-4-oxoheptanoylamino]-5-(2"'
      oxopyrrolidin-3-"'-yl)pent-2-enoic acid ethyl ester] was studied in liver
      microsomes isolated from mice, rats, rabbits, dogs, monkeys, and humans. The
      structures of the metabolites were characterized by liquid chromatography (LC)
      tandem mass spectrometry and LC-NMR methods. Hydrolysis of the ethyl ester to
      produce metabolite M4 (AG7185) is the predominant pathway in all species, with
      the greatest activity observed in rodents and rabbits, followed by monkeys, dogs,
      and humans. Several hydroxylation products were identified as minor metabolites,
      including diastereomers M1 and M2, with a hydroxy group at the P1-lactam moiety,
      and M3, with a hydroxy group at the methyl position of the methylisoxazole ring.
      Rodent and rabbit liver microsomes formed almost exclusively the acid metabolite
      M4 (AG7185), with very little hydroxylated metabolites, whereas monkey liver
      microsomes formed more secondary metabolites (i.e., acid analogs of the
      hydroxylated metabolites). The overall metabolic profile of AG7088 formed in dog
      liver microsomes closely resembled that of human liver microsomes; therefore,
      this species may be the most appropriate animal model relative to humans for
      exposure to AG7088 and its metabolites.

PMID- 11302942
TI  - Effects of receptor-selective retinoids on CYP26 gene expression and metabolism
      of all-trans-retinoic acid in intestinal cells.
AB  - Retinoids mediate most of their function via interaction with retinoid receptors
      [retinoic acid receptors (RARs) and retinoid X receptors (RXRs)], which act as
      ligand-activated transcription factors controlling the expression of a number of
      target genes. The complex mechanistic pattern of retinoid-induced effects on gene
      expression of CYP26 and intestinal metabolism of all-trans-retinoic acid (RA) was
      investigated here by studying the effects of retinoid ligands with relative
      selectivity for binding and transactivation of the retinoid acid receptors, RARs
      and RXRs, in human intestinal Caco-2 cells. We show here that CYP26 is expressed
      in human duodenum and colon. In Caco-2 cells not only all-trans-RA but also
      synthetic agonists of the RAR induced intestinal CYP26 gene expression and all
      trans-RA metabolism as well. The RARalpha ligand Am580 induced the CYP26 gene
      expression more than the RARbeta ligand CD2019 or the RARgamma ligand CD437
      suggesting the highest specificity for RARalpha on intestinal CYP26 gene
      regulation. RXR ligands alone did not induce CYP26 gene expression or RA
      metabolism in Caco-2 cells at all. But together with the RARalpha ligand, Am580,
      there were enhanced effects on the induction of CYP26 gene expression and on the
      induction of the metabolism of all-trans-RA. We conclude that gene regulation of
      CYP26 and the metabolism of all-trans-RA in intestinal cells is regulated through
      RXR and RAR heterodimerization. When coadministered, RAR agonists showed the
      highest potency for CYP26 gene regulation. Receptor-selective retinoids showed
      enhanced effects on induction of CYP26 gene expression and all-trans-retinoic
      acid metabolism.

PMID- 11302943
TI  - Inhibition of CYP3A4 in a rapid microtiter plate assay using recombinant enzyme
      and in human liver microsomes using conventional substrates.
AB  - Cytochrome P450 inhibition studies are performed in the pharmaceutical industry
      in the discovery stage to screen candidates that may have the potential for
      clinical drug-drug interactions. A 96-well microtiter plate assay using
      recombinant cytochrome P450 (Supersomes) has been used to increase the overall
      throughput. The IC(50) values for the inhibition of CYP3A4 by 52 new chemical
      entities (NCEs) were determined using the Supersomes assay with resorufin benzyl
      ether as a substrate, and the data were compared with those obtained in human
      liver microsomes (HLM) using midazolam as a substrate. Among the 52 compounds
      tested, 25 showed IC(50) values within a 5-fold difference in the two assays. For
      all compounds that showed a >5-fold difference, the IC(50) values in the
      Supersomes assay were lower than those obtained in HLM, except for one compound.
      Further studies suggested that this discrepancy was not related to difference in
      protein concentrations between the two assays. In addition, the IC(50) values for
      16 compounds with a wide range of inhibition potency were determined in HLM using
      testosterone and dextromethorphan as substrates. The results showed an 80 to 93%
      match within a 5-fold difference between the three probe substrates. However, for
      certain compounds including ketoconazole, there were substrate-dependent
      differences in the inhibition. The results suggest that the difference between
      the Supersomes and HLM could be partially attributed to differences in the
      substrate used, and to metabolism by other cytochrome P450s present in the HLM
      but not in the Supersomes. Furthermore, multiple CYP3A4 substrates should be used
      to improve the reliability of estimating potential drug-drug interaction of NCEs.

PMID- 11302944
TI  - Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhibitors.
AB  - P-Glycoprotein (Pgp) and cytochrome P450 3A (CYP3A) are important enzymes
      affecting the disposition of HIV protease inhibitors (HIV PIs). After multiple
      dosing experiments in rats, decreases in the plasma concentrations and area under
      plasma concentration-time curve (AUC) for HIV PIs have been observed. The purpose
      of these studies was to determine the changes in Pgp and CYP3A expression and HIV
      PI plasma exposure after multiple doses of HIV PIs. Male rats were orally dosed
      with an amprenavir prodrug (450 mg/kg/day amprenavir-equivalent) or nelfinavir
      (175 mg/kg/day) for 1 or 14 days. Relative to day 1, the C(max) and the AUC for
      amprenavir at day 14 were decreased by 33 and 51%, respectively. Similarly, the
      plasma concentration of nelfinavir at 1 h after the last dose (C(max)) was
      reduced by 52% after multiple doses. Compared with controls, dosing of amprenavir
      for 14 days increased intestinal Pgp and hepatic CYP3A protein levels by 59 and
      151%, respectively, but did not alter intestinal CYP3A protein levels. In
      contrast, amprenavir treatment did not result in an increase in hepatic CYP3A
      activity. Nelfinavir treatment increased expression of intestinal Pgp and hepatic
      CYP3A levels by 83 and 85%, respectively, but not hepatic Pgp or intestinal
      CYP3A. HIV PIs also induced Pgp expression in the LS174T human intestinal cell
      line. These results indicate that HIV protease inhibitors induce both intestinal
      Pgp and hepatic CYP3A and suggest that induction of Pgp and CYP3A is a possible
      mechanism reducing drug exposure after multiple doses.

PMID- 11302945
TI  - Verapamil metabolism in distinct regions of the heart and in cultures of
      cardiomyocytes of adult rats.
AB  - A substantial number of drugs act either directly or indirectly on the heart, but
      surprisingly, little is known about drug oxidation in the heart. We therefore
      investigated the metabolism of the calcium antagonist verapamil in microsomal
      fractions isolated from the left and right ventricle of heart muscle and in
      primary cultures of cardiomyocytes of adult rats. Metabolism of verapamil
      proceeded predominantly with microsomal fractions isolated from the right
      ventricle of rat heart, and in liquid chromatographic-tandem mass spectrometry
      (LC-MS/MS) and LC-MS(3) experiments four metabolites (M1-M4) could be identified.
      Furthermore, the intermediate biotransformation products M5 to M8 could
      additionally be identified in cultures of primary cardiomyocytes, thus providing
      new insight into the mechanisms of the N-dealkylation and O-demethylation pathway
      of verapamil. We show metabolism of verapamil to be predominant in the right
      ventricle of the heart, and the data reported herein may explain metabolic
      inactivation and/or adverse drug reactions of certain cardiovascular drugs on the
      basis of tissue specific metabolism.

PMID- 11302946
TI  - Pharmacokinetics of budesonide and its major ester metabolite after inhalation
      and intravenous administration of budesonide in the rat.
AB  - Fatty acid esterification of budesonide (BUD) has previously been documented in
      vitro as well as in large airway tissues after in vivo administration. This
      reversible esterification has the potential to prolong the anti-inflammatory
      effect of BUD and improve its airway selectivity. In the present study we
      characterized the plasma and tissue kinetics of BUD in the rat after inhalation
      and intravenous administration, and fitted a semiphysiological compartment model
      to the data. After inhalation, BUD half-life was longer (8.2 h) in trachea than
      in plasma (3.7 h), with similar data after intravenous dosing. BUD-oleate was
      formed in all tissues and had a longer half-life than BUD in trachea (18-20 h)
      but a similar half-life in plasma and muscle. Although the major fraction of BUD
      and BUD-oleate in the body was found in muscle, the airways, especially trachea,
      possessed a high capacity to form BUD-oleate. According to steady-state
      simulations, BUD-oleate accumulated in trachea, giving rise to persistent and
      higher concentrations of active BUD as compared with a situation wherein esters
      were not formed. BUD esters had no effect on plasma levels of BUD at steady
      state, however. BUD and BUD-oleate were shown to have a 2-fold and 10- to 50-fold
      selectivity, respectively, in airways as compared with muscle tissue after
      intravenous administration. After inhalation, the corresponding figures for
      selectivity were 10 and 50 to 1000, respectively.

PMID- 11302947
TI  - Some of the challenges in drug development for irritable bowel syndrome.

PMID- 11302948
TI  - Dietary fibre and the risk of colorectal cancer.

PMID- 11302949
TI  - Helicobacter pylori, harmful to the brain?

PMID- 11302950
TI  - Rational dosing of azathioprine and 6-mercaptopurine.

PMID- 11302951
TI  - New pouches for old?

PMID- 11302952
TI  - Landscaper seeks remunerative position.

PMID- 11302953
TI  - Serotonin receptor modulation in irritable bowel syndrome: one step forwards and
      one step backwards.

PMID- 11302954
TI  - Helicobacter pylori infection induced alteration of gene expression in human
      gastric cells.
AB  - BACKGROUND: Helicobacter pylori, a human pathogen responsible for many digestive
      disorders, induces complex changes in patterns of gene expression in infected
      tissues. cDNA expression arrays provide a useful tool for studying these complex
      phenomena. AIM: To identify genes that showed altered expression after H pylori
      infection of human gastric cells compared with uninfected controls. METHODS: The
      gastric adenocarcinoma cell line AGS was cocultivated with H pylori. Growth of
      infected cells was determined by trypan blue exclusion assay. Complementary DNA
      probes derived from H pylori treated and untreated cells were hybridised to two
      identical Atlas human cDNA expression arrays, and those genes with altered
      expression levels were identified. A real time quantitative reverse transcription
      polymerase chain reaction assay was used to better define expression patterns of
      these genes in endoscopically gastric mucosal biopsies with and without H pylori
      infection. RESULTS: Over 24 hours, coincubation with H pylori inhibited AGS cell
      growth but did not cause a noticeable degree of cell death. H pylori treatment
      altered the pattern of gene expression in AGS cells. We identified 21
      overexpressed genes and 17 suppressed genes from the cDNA expression arrays. The
      majority of genes were transcription factors such as c-jun, BTEB2, and ETR101.
      Other genes were involved in signal transduction pathways, such as MAP kinase,
      interleukin 5, and insulin-like growth factor. Genes involved in cell cycle
      regulation and differentiation, such as CDC25B and NM23-H2, were also identified.
      In patients with H pylori infection (n=20), there was a significant difference
      for ERCC3, Id-2, and NM23-H2 mRNA levels in infected gastric mucosa compared with
      uninfected gastric mucosa in patients without peptic diseases (n=20) (ERCC3 4.75
      molecules/10(4) beta-actin mRNA molecules v 13.65, p<0.001; Id-2 16.1 v 23.4,
      p<0.05; NM23-H2 17.5 v 45.5, p<0.001). There was no significant difference
      between mRNA levels of c-jun and CDC25B in H pylori colonised gastric mucosa and
      uninfected mucosa. CONCLUSION: We demonstrated that H pylori infection caused
      alteration of gene expression in AGS cells. The differential hybridisation
      technique of Atlas human cDNA expression array is a useful method to identify
      host genes involved in pathogenic mechanisms in H pylori infection.

PMID- 11302955
TI  - Helicobacter pylori infection induces hyperammonaemia in Mongolian gerbils with
      liver cirrhosis.
AB  - BACKGROUND AND AIMS: We previously reported the effect of Helicobacter pylori
      eradication on hyperammonaemia in patients with liver cirrhosis. However, the
      role of H pylori as a cause of hyperammonaemia is controversial. We developed an
      animal model with liver cirrhosis and investigated the effect of H pylori
      infection on hyperammonaemia. MATERIALS AND METHODS: Five week old male Mongolian
      gerbils were inoculated orally with broth culture of H pylori. Forty eight
      gerbils were divided into four groups. Gerbils not inoculated with H pylori were
      fed a commercial rodent diet (group A) or a choline deficient diet (group C).
      Gerbils inoculated with H pylori were fed the commercial rodent diet (group B) or
      the choline deficient diet (group D). Blood ammonia levels of the femoral vein
      and portal vein were measured 30 weeks later. RESULTS: All gerbils fed the
      choline deficient diet developed liver cirrhosis with fatty metamorphosis. The
      survival rate of group D was significantly lower than that of the other groups.
      Systemic and portal blood ammonia levels in group D were significantly higher
      than those in the other groups. CONCLUSIONS: H pylori infection induces
      hyperammonaemia in gerbils with liver cirrhosis.

PMID- 11302956
TI  - Probiotics in inflamatory bowel disease.

PMID- 11302957
TI  - Absence of endogenous interleukin 10 enhances early stress response during post
      ischaemic injury in mice intestine.
AB  - BACKGROUND: Interleukin 10 (IL-10) exerts a wide spectrum of regulatory
      activities in immune and inflammatory responses. AIMS: The aim of this study was
      to investigate the role of endogenous IL-10 on modulation of the early
      inflammatory response after splanchnic ischaemia and reperfusion. METHODS:
      Intestinal damage was induced by clamping the superior mesenteric artery and the
      coeliac trunk for 45 minutes followed by reperfusion in IL-10 deficient mice (IL
      10(-/-)) and wild-type controls. RESULTS: IL-10(-/-) mice experienced a higher
      rate of mortality and more severe tissue injury compared with wild-type mice
      subjected to ischaemia and reperfusion. Splanchnic injury was characterised by
      massive epithelial haemorrhagic necrosis, upregulation of P-selectin and
      intercellular adhesion molecule 1, and neutrophil infiltration. The degree of
      oxidative and nitrosative damage was significantly higher in IL-10(-/-) mice than
      in wild-type littermates, as indicated by elevated malondialdehyde levels and
      formation of nitrotyrosine. Plasma levels of the proinflammatory cytokines tumour
      necrosis factor alpha and interleukin 6 were also greatly enhanced in comparison
      with wild-type mice. These events were preceded by increased immunostaining and
      activity of the stress regulated c-Jun NH(2) terminal kinase and activation of
      the transcription factor activator protein 1 in the cellular nuclei of damaged
      tissue. CONCLUSIONS: These data demonstrate that endogenous IL-10 exerts an anti
      inflammatory role during reperfusion injury, possibly by regulating early stress
      related genetic response, adhesion molecule expression, neutrophil recruitment,
      and subsequent cytokine and oxidant generation.

PMID- 11302958
TI  - Upregulation of Reg 1alpha and GW112 in the epithelium of inflamed colonic
      mucosa.
AB  - BACKGROUND AND AIMS: Colonic epithelium is involved in the regulation of
      intestinal function and mucosal immune responses, and its function is altered in
      inflammatory bowel disease (IBD). However, a comprehensive analysis of the
      genetic alterations in inflamed colonic epithelium is not available at present.
      The aim of our study was to detect genes that are preferentially expressed in
      inflamed colonic epithelia and clarify the biochemical responses of epithelial
      cells in inflamed colonic mucosa. METHODS: cDNA representation difference
      analysis was used to identify candidate genes selectively expressed in inflamed
      colonic epithelia. Selective expression of these genes in the epithelium of
      inflamed colonic mucosa, including IBD and non-IBD tissues, was examined by real
      time polymerase chain reaction and in situ hybridisation. The effect of cell
      confluence and inflammatory mediators on Reg 1alpha gene expression was examined
      using a colon cancer cell line (HT29). RESULTS: We identified seven candidate
      genes that were presumed to be upregulated in the inflamed colonic epithelium. Of
      these, Reg 1alpha and GW112 were the dominant species and expression of these
      genes was confined to the crypt epithelium. In vitro studies using a colonic
      epithelial cell line suggested that cell confluence regulates Reg 1alpha gene
      expression. CONCLUSIONS: Selective expression of Reg 1alpha and GW112 genes in
      the crypt epithelium of inflamed colonic mucosa suggests the important regulatory
      functions of these genes.

PMID- 11302959
TI  - Role of mast cells in chronic stress induced colonic epithelial barrier
      dysfunction in the rat.
AB  - BACKGROUND AND AIMS: Stress may be an important factor in exacerbating
      inflammatory bowel disease but the underlying mechanism is unclear. Defective
      epithelial barrier function may allow uptake of luminal antigens that stimulate
      an immune/inflammatory response. Here, we examined the effect of chronic stress
      on colonic permeability and the participation of mast cells in this response.
      METHODS: Mast cell deficient Ws/Ws rats and +/+ littermate controls were
      submitted to water avoidance stress or sham stress (one hour/day) for five days.
      Colonic epithelial permeability to a model macromolecular antigen, horseradish
      peroxidase, was measured in Ussing chambers. Epithelial and mast cell morphology
      was studied by light and electron microscopy. RESULTS: Chronic stress
      significantly increased macromolecular flux and caused epithelial mitochondrial
      swelling in +/+ rats, but not in Ws/Ws rats, compared with non-stressed controls.
      Stress increased the number of mucosal mast cells and the proportion of cells
      showing signs of activation in +/+ rats. No mast cells or ultrastructural
      abnormalities of the epithelium were present in Ws/Ws rats. Increased
      permeability in +/+ rats persisted for 72 hours after stress cessation.
      CONCLUSIONS: Chronic stress causes an epithelial barrier defect and epithelial
      mitochondrial damage, in parallel with mucosal mast cell hyperplasia and
      activation. The study provides further support for an important role for mast
      cells in stress induced colonic mucosal pathophysiology.

PMID- 11302960
TI  - No evidence of persistent mumps virus infection in inflammatory bowel disease.
AB  - BACKGROUND AND AIM: There is controversy regarding whether paramyxovirus
      infection is causally associated with inflammatory bowel disease (IBD). The
      latest cohort study claimed that atypical measles and mumps infections in
      childhood may be risk factors for later IBD. This study was conducted to clarify
      the validity of a causal link between persistent mumps virus infection and IBD.
      SUBJECTS AND METHODS: (1) Amplification of the mumps virus genome was performed
      in both intestinal specimens (ulcerative colitis 15, Crohn's disease 15, control
      10) and peripheral blood lymphocytes (PBL) (ulcerative colitis seven, Crohn's
      disease six, control three) by reverse transcription-polymerase chain reaction
      (RT-PCR) followed by Southern hybridisation using primers specific to the viral
      genome encoding phosphoprotein or haemagglutinin-neuraminidase. (2) Titre of
      serum antimumps IgG was measured in 16 patients with ulcerative colitis, in 16
      patients with Crohn's disease, and in 16 normal controls using an enzyme linked
      immunosorbent assay. RESULTS: (1) The mumps virus genome was not detected by RT
      PCR in intestinal specimens or PBL in any case. (2) Antimumps IgG titre was
      positive in 7/16 ulcerative colitis, 10/16 Crohn's disease, and 11/16 control
      specimens. The mean (SEM) titre of antimumps IgG was 12.281 (7.831) in ulcerative
      colitis, 7.675 (1.608) in Crohn's disease, and 8.637 (1.969) in controls, with no
      significant difference between the three groups. CONCLUSION: We could not find
      any evidence to support a causal link between persistent mumps virus infection
      and IBD.

PMID- 11302962
TI  - Antibiotics in Crohn's disease.

PMID- 11302961
TI  - Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise
      azathioprine therapy in patients with inflammatory bowel disease.
AB  - BACKGROUND AND AIM: The immunosuppressive properties of 6-mercaptopurine and its
      parent compound azathioprine are mediated by their intracellular metabolism into
      active 6-thioguanine (6-TG) metabolites. Measurement of erythrocyte 6-TG
      metabolite levels has been proposed as a useful clinical tool for assessing
      treatment efficacy in patients with inflammatory bowel disease (IBD). AIM: The
      purpose of the study was to establish a therapeutic index of treatment efficacy
      based on measurement of erythrocyte 6-TG metabolite levels, and apply it
      clinically to guide therapy. METHODS: Heparinised blood was obtained from 82
      adult patients with IBD on long term (more than three months) antimetabolite
      therapy (63 Crohn's disease; 19 ulcerative colitis). Erythrocyte 6-TG metabolite
      levels were measured using reverse phase high performance chromatography, and
      correlated with treatment efficacy. In 22 patients with refractory Crohn's
      disease despite long term azathioprine therapy, their dosage was increased by 25
      mg/day at eight week intervals as needed. Serial erythrocyte 6-TG metabolite
      levels were measured at each clinic visit and correlated with treatment efficacy.
      RESULTS: Clinical remission, as defined by a low disease index score in patients
      weaned off or on a low alternate day dose (<20 mg on alternate days) of
      corticosteroid, was achieved in 68% of patients on long term antimetabolite
      therapy. Treatment efficacy correlated with erythrocyte 6-TG levels greater than
      250 pmol/8x10(8) red blood cells in patients with colonic and fistulising Crohn's
      disease (p<0.01) but not in patients with ileocolonic disease. Eighteen of 22
      patients with incompletely responsive Crohn's disease achieved disease remission
      by optimising their dose of azathioprine therapy. Median (range) erythrocyte 6-TG
      metabolite levels increased from 194 (67-688) to 303 (67-737) pmol/8x10(8) red
      blood cells (p<0.05). Clinical response associated well with a reduction in
      corticosteroid requirements. Mean (SEM) white blood cell count decreased from 8.6
      (0.9) to 6.9 (0.6) x10(3)/microl with adjustment in azathioprine dosage. No
      patient incurred azathioprine induced leucopenia. CONCLUSION: Measurement of
      erythrocyte 6-TG metabolite levels is helpful in determining the adequacy of
      azathioprine dosage and can be used to optimise the dose of antimetabolite
      therapy to achieve an improved clinical response without inducing leucopenia.
      Patients who are clinically refractory to azathioprine therapy despite achieving
      high erythrocyte 6-TG levels (>250) should be considered for adjunct or
      alternative forms of immunosuppressive therapy or surgery.

PMID- 11302963
TI  - Dramatic diurnal variation in the concentration of the human trefoil peptide TFF2
      in gastric juice.
AB  - BACKGROUND: TFF2, a member of the trefoil factor family of proteins, is a
      glycosylated protein of 106 amino acids. It is secreted by gastric antral and
      pyloric glands and by Brunner's glands of the duodenum. TFF2 is found in high
      concentrations around sites of ulceration. It stimulates cell motility and is
      probably the principal cytoprotective trefoil peptide in the stomach. AIMS: To
      determine if production of TFF2 follows a circadian rhythm and to measure changes
      in secretion of TFF2 in response to food intake and during sleep. SUBJECTS: Young
      healthy adults were recruited. They were asymptomatic and were not receiving
      medication. The 24 hour regimen was designed to allow normal stimulation of
      gastric secretion in response to food intake and sleep. Gastric juice was
      collected two hourly via a nasogastric tube. METHODS: Glycosylated and non
      glycosylated TFF2 proteins were measured by quantitative western transfer
      analysis. The results were analysed statistically using SPSS software. RESULTS:
      There was a dramatic diurnal variation in the concentration of TFF2. The mean
      concentration was lowest in the early evening (0.29 microg/ml), increased
      gradually during the evening, and then sharply during the night to reach 7.9
      microg/ml. The ratio of glycosylated to non-glycosylated TFF2 varied and was
      higher during the night than in the afternoon. pH, total protein, and pepsin
      concentrations in gastric juice did not vary significantly over 24 hours.
      CONCLUSION: The data suggest that diurnal variations in TFF2 secretion occur
      independently of pepsin and gastric acid secretion. The concentration of
      glycosylated TFF2 in the gastric lumen falls in response to food intake. TFF2
      secretion increases during inactivity and sleep. These results suggest that
      secretion of TFF2 in the stomach is highest during the night and that the
      cytoprotective effects of TFF2 on the gastric mucosa occur mainly during sleep.

PMID- 11302964
TI  - Genetic alterations and growth pattern in biliary duct carcinomas: loss of
      heterozygosity at chromosome 5q bears a close relation with polypoid growth.
AB  - Biliary duct carcinomas (BDCs) are relatively rare and the carcinogenic
      mechanisms underlying their induction are poorly understood. There are two growth
      patterns, polypoid and non-polypoid infiltrative type, but little information is
      available concerning the relation between growth pattern and genetic alterations.
      A comparative study was therefore conducted to clarify if differences in genetic
      changes, including loss of heterozygosity (LOH) at 5q, 9p, 17p, and 18q, and K
      ras mutations exist between polypoid and non-polypoid infiltrative type BDCs. LOH
      analysis was performed using microsatellite markers and K-ras point mutations
      were analysed by dot blot hybridisation. The incidences of changes for polypoid
      and non-polypoid infiltrative types were 73% and 26% on 5q, 63% and 59% on 9p,
      55% and 50% on 17p, and 20% and 18% on 18q, and 25% and 27% for K-ras mutations.
      Most importantly, we found the frequency of 5qLOH to be significantly higher with
      polypoid growth than in the non-polypoid infiltrative type (p<0.05), especially
      in extrahepatic duct carcinomas (p<0.05). The incidences of other genetic
      alterations (LOH at 9p, 17p, and 18q, and K-ras mutations) showed similar rates
      with both tumour types. The present data suggest that 5qLOH may have a close
      relation with polypoid growth in BDCs.

PMID- 11302966
TI  - Circumferential resection margin involvement: an independent predictor of
      survival following surgery for oesophageal cancer.
AB  - BACKGROUND: For rectal carcinoma, the presence of tumour within 1 mm of the
      circumferential margin is an important independent prognostic factor for both
      local recurrence and survival. Similar prospective data have not been reported
      for oesophageal carcinoma and we wished to ascertain the prognostic importance of
      this variable following potentially curative resection for oesophageal carcinoma.
      AIM: To prospectively assess the impact of circumferential margin involvement
      (tumour within 1 mm) following potentially curative resection for oesophageal
      carcinoma. PATIENTS AND METHODS: In a prospective study, resection specimens of
      135 patients treated with potentially curative oesophageal resection alone were
      studied for the presence of tumour within 1 mm of the circumferential margin
      (margin positive), using inked margins and cross sectional slicing of the
      specimen. All tumours were also staged using the 1987 UICC TNM classification.
      Patients were followed for a mean of 19 months, and overall and cancer specific
      survival analysed. RESULTS: The finding of tumour cells within 1 mm of the
      circumferential margin (CRM+) was a significant and independent predictor of
      survival following potentially curative oesophageal resection. Overall, 64 (47%)
      patients were CRM+. Median survival in this group was 21 months compared with 39
      months in the CRM- group (p=0.015). The impact of CRM status on survival was only
      seen in patients with a low nodal metastatic burden (<25% nodes positive). The
      odds ratio for the risk of dying from oesophageal cancer was 2.08 when the CRM
      was involved (p=0.013). CONCLUSIONS: The presence of tumour within 1 mm of the
      circumferential margin following potentially curative resection for oesophageal
      carcinoma is an important independent prognostic variable and should be reported
      routinely.

PMID- 11302965
TI  - Non-steroidal anti-inflammatory drugs with activity against either cyclooxygenase
      1 or cyclooxygenase 2 inhibit colorectal cancer in a DMH rodent model by inducing
      apoptosis and inhibiting cell proliferation.
AB  - BACKGROUND: Standard non-steroidal anti-inflammatory drugs (NSAIDs) reduce the
      risk of colorectal cancer by 40-60% but the mechanism by which this occurs is
      uncertain. Selective cyclooxygenase 2 inhibitors are potentially ideal
      chemopreventive agents as they are less toxic than standard NSAIDs. No study has
      compared the efficacy of these drugs at clinically relevant doses in a tumour
      model. AIMS: To assess the efficacy of a range of NSAIDs with varying activity
      against the two cyclooxygenase isoforms in a rodent colorectal carcinogen model
      at anti-inflammatory doses and to explore the effect of NSAIDs on the rate of
      tumour apoptosis and proliferation. METHODS: Colorectal tumours were induced in
      six week old Sprague-Dawley rats with five weekly doses of 1,2 dimethylhydrazine.
      Test agents were: indomethacin 2 mg/kg/day, meloxicam 0.6 mg/kg/day, celecoxib 6
      mg/kg/day, and sulindac sulphone 40 mg/kg/day. Sulindac was tested at its
      chemoprotective dose of 20 mg/kg/day. After 23 weeks the number and volume of
      tumours per animal were recorded. Histology was performed. Tumour apoptosis was
      quantified on haematoxylin-eosin sections. Tumour proliferation was quantified
      using an immunohistochemical stain for bromodexoyuridine incorporation. RESULTS:
      Test agents effectively reduced the number and volume of tumours developing in
      the treatment period. In all groups there was an increase in the rate of tumour
      apoptosis and a reduced rate of proliferation. CONCLUSIONS: These data suggest
      that the chemopreventive effect of NSAIDs is independent of their cyclooxygenase
      inhibitory profile. One potential mechanism for their action may be through
      induction of apoptosis and inhibition of proliferation.

PMID- 11302967
TI  - Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal
      neuronal dysplasia and Hirschsprung disease.
AB  - BACKGROUND: Hirschsprung disease (HSCR) is a frequent congenital disorder with an
      incidence of 1 in 5000 live births, characterised by the absence of
      parasympathetic intramural ganglion cells in the hindgut resulting in intestinal
      obstruction in neonates and severe constipation in infants and adults. Intestinal
      neuronal dysplasia (IND) shares clinical features with HSCR but the submucosal
      parasympathetic plexus is affected. IND has been proposed as one of the most
      frequent causes of chronic constipation and is often associated with HSCR.
      METHODS: We examined 29 patients diagnosed with sporadic HSCR, 20 patients with
      IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of
      the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by
      single strand conformational polymorphism and DNA sequencing. RESULTS: Only three
      RET mutations were detected in patients with HSCR. In patients with IND or a
      mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR
      and HSCR/IND showed over representation of a specific RET polymorphism in exon 2,
      IND exhibited a significantly lower frequency comparable with that of controls.
      CONCLUSIONS: The mutation frequency found in our sporadic HSCR patients (10%) and
      the allelic distribution of RET polymorphisms are comparable with earlier
      published data. A significantly different allelic distribution in an established
      HSCR associated polymorphism argues against common genetic pathways for HSCR and
      IND.

PMID- 11302968
TI  - Effects of octreotide on responses to colorectal distension in the rat.
AB  - BACKGROUND AND AIMS: It has been suggested that the analgesic effect of the
      somatostatin analogue octreotide in visceral pain involves peripheral mechanisms.
      We evaluated the effect of octreotide on responses to noxious colorectal
      distension in rats. METHODS: In a behavioural study, pressor and
      electromyographic responses to colorectal distension were evaluated before and
      after intravenous or intrathecal administration of octreotide. In pelvic nerve
      afferent fibre recordings, responses of mechanosensitive fibres innervating the
      colon to noxious colorectal distension (80 mm Hg, 30 seconds) were tested before
      and after octreotide. RESULTS: Octreotide was ineffective in attenuating
      responses to colorectal distension in either normal or acetic acid inflamed colon
      when administered intravenously but attenuated responses when given
      intrathecally. Administration of octreotide over a broad dose range (0.5
      microg/kg to 2.4 mg/kg) did not alter responses of afferent fibres to noxious
      colorectal distension in untreated, or acetic acid or zymosan treated colons.
      CONCLUSIONS: In the rat, octreotide has no peripheral (pelvic nerve) modulatory
      action in visceral nociception. The antinociceptive effect of octreotide in this
      model of visceral nociception is mediated by an action at central sites.

PMID- 11302969
TI  - Functional results and visceral perception after ileo neo-rectal anastomosis in
      patients: a pilot study.
AB  - INTRODUCTION: To reduce pouch related complications after restorative
      proctocolectomy, an alternative procedure was developed, the ileo neo-rectal
      anastomosis (INRA). This technique consists of rectal mucosa replacement by ileal
      mucosa and straight ileorectal anastomosis. Our study provides a detailed
      description of the functional results after INRA. PATIENTS AND METHODS: Eleven
      patients underwent an INRA procedure with a temporary ileostomy. Anorectal
      function tests were performed two months prior to and six and 12 months after
      closure of the ileostomy and comprised: anal manometry, ultrasound examination,
      rectal balloon distension, and transmucosal electrical nerve stimulation (TENS).
      Function was subsequently related to the histopathology of rectal biopsy samples.
      RESULTS: Median stool frequency decreased from 15/24 hours (10-25) to 6/24 hours
      (4-11) at one year. All patients reported full continence. Anal sensibility, and
      resting and squeeze pressures did not change after INRA. Rectal compliance
      decreased (2.1 (0.7-2.8) v 1.5 (0.4-2.2) and 1.4 (0.8-3.7) ml/mm Hg (p=0.03)) but
      the maximum tolerated volume increased (70 (50-118) v 96 (39-176) (NS) and 122
      (56-185) ml (p=0.03)). Decreasing rectal sensitivity was found: the maximum
      tolerated pressure increased (14 (8-24) v 22 (8-34) (NS) and 26 (14-40) (p=0.02))
      and the rectal threshold for TENS displayed a similar tendency. All patients
      displayed a low grade chronic inflammatory infiltrate in neorectal biopsy samples
      before closure of the ileostomy, with no change during follow up. CONCLUSIONS:
      The technique of INRA provides a safe alternative for restorative surgery. Stool
      frequency after INRA improves with time and seems to be related to decreasing
      sensitivity and not to histopathological changes in the neorectum. Furthermore,
      after the INRA procedure, all patients reported full continence.

PMID- 11302970
TI  - Modification of small bowel mechanosensitivity by intestinal fat.
AB  - BACKGROUND: Lipids may exacerbate symptoms induced by gut stimuli. AIM: To
      determine the mechanism whereby fat exerts this effect. SUBJECTS: Twenty four
      healthy subjects were studied during fasting. METHODS: We measured perception (0
      6 scale) in response to jejunal balloon distension and transmucosal electrical
      nerve stimulation; phasic stimuli (one minute) were randomly applied at five
      minute intervals during intestinal infusion (2 ml/min) of saline and then
      Intralipid 2 kcal/min (high fat; n=8 subjects), Intralipid 0.5 kcal/min (low fat;
      n=8), or saline (n=8). RESULTS: Intestinal lipids increased the perception of
      jejunal distension regardless of concentration (by 53% with high fat, 49% with
      low fat, and 17% with saline; p<0.05 for both fat loads). This effect could not
      be attributed to changes in intestinal compliance as intraballoon pressures
      remained unchanged during lipid infusion (2% change; NS). Sensitisation induced
      by lipids seemed to be specifically related to intestinal mechanoreceptors
      because electrical stimulation, which non-specifically activates gut afferents,
      was perceived equally during saline and lipid administration (10%, 11%, and 15%
      change during high fat, low fat, and saline, respectively; NS). CONCLUSION:
      Physiological amounts of lipids heighten intestinal sensitivity by modulating
      intestinal mechanoreceptor response.

PMID- 11302971
TI  - Candidate gene regions and genetic heterogeneity in gluten sensitivity.
AB  - BACKGROUND: Gluten sensitivity is a common multifactorial disorder, manifested in
      the small intestine or on the skin as typical coeliac disease or dermatitis
      herpetiformis, respectively. The only established genetic risk factor is HLA DQ2.
      AIMS: We tested genetic linkage of previously reported chromosomal loci 5q and
      11q in Finnish families with gluten sensitivity. We also tested if genetic
      linkage to candidate loci on 5q, 11q, 2q33, and HLA DQ differed with respect to
      clinical manifestations or sex. SUBJECTS: We studied 102 Finnish families with
      affected sibpairs. For heterogeneity analysis, families were divided into
      subgroups according to sex and the presence of dermatitis herpetiformis, the skin
      manifestation of gluten sensitivity. METHODS: Non-parametric linkage between
      microsatellite markers and disease was tested. Linkage heterogeneity between
      subgroups was tested using the M test. The transmission/disequilibrium test and
      association analysis were performed. RESULTS: Evidence of linkage to 11q (MLS
      1.37), but not to 5q, was found in the entire dataset of 102 families.
      Heterogeneity between subgroups was suggested: families with only the intestinal
      disease showed linkage mainly to 2q33 whereas families with dermatitis
      herpetiformis showed linkage to 11q and 5q, but not to 2q33. Linkage in all three
      non-HLA loci was strongest in families with predominantly male patients. HLA DQ2
      conferred much stronger susceptibility to females than males. CONCLUSIONS:
      Independent evidence for the suggested genetic linkage between 11q and gluten
      sensitivity was obtained. The possible linkage heterogeneity suggests genetic
      differences between intestinal and skin manifestations, and the gender dependent
      effect of HLA DQ2.

PMID- 11302972
TI  - Biliary lipid composition in cholesterol microlithiasis.
AB  - BACKGROUND: Little information is available on the pathogenesis of cholesterol
      microlithiasis, and it is not clear if biliary lipid composition in these
      patients is similar to changes seen in cholesterol gall stone patients. AIMS: To
      measure biliary lipid composition in patients with cholesterol microlithiasis.
      PATIENTS: Eleven patients with cholesterol microlithiasis, 20 cholesterol gall
      stone patients, and 17 healthy controls. METHODS: Duodenal bile was collected in
      the fasting state during ceruletide infusion. Biliary cholesterol, phospholipids,
      and total bile acids were analysed by enzymatic assays, and conjugated bile acids
      by high pressure liquid chromatography. RESULTS: Patients with microlithiasis had
      a cholesterol saturation index significantly higher than controls (mean value
      1.30 (95% confidence interval 1.05-1.54) v 0.90 (0.72-1.08)) but similar to gall
      stone patients (1.51 (1.40-1.63)). This was due to a significant decrease in per
      cent phospholipid (10.0% (7.1-12.8)) compared with controls (21.4% (18.1-24.6))
      and gall stone patients (24.9% (20.5-29.3)). Per cent cholesterol was similar in
      patients with microlithiasis and controls (5.3% (4.5-6.1) and 5.6 % (4.3-6.8),
      respectively) but was significantly increased in gall stone patients (10.9% (9.3
      12.4)). Bile acid composition in patients with microlithiasis was similar to
      controls whereas in gall stone patients deoxycholic acid was significantly
      increased: 27.3% (24.8-29.7) v 19.0% (15.7-22.2) in controls and 20.6% (14.9
      26.2) in patients with microlithiasis. CONCLUSION: Patients with cholesterol
      microlithiasis have biliary cholesterol supersaturation, similarly to cholesterol
      gall stone patients. Whereas in the latter this is due to increased per cent
      cholesterol, in patients with microlithiasis this is caused by phospholipid
      deficiency, with normal per cent cholesterol and normal biliary bile acid
      composition.

PMID- 11302973
TI  - The epidemiology of hepatitis C in a UK health regional population of 5.12
      million.
AB  - BACKGROUND: The epidemiology and natural history of hepatitis C virus (HCV)
      infection in the UK are uncertain. Previous reports are from small or selected
      populations such as blood donors or tertiary referral centres. AIMS: To study the
      epidemiology and natural history of HCV infection. METHODS: Prospective study
      incorporating five centres within the Trent region. Patients were managed and
      followed up according to a commonly agreed protocol. SUBJECTS: A total of 1128
      HCV positive patients. Patients with haemophilia, human immunodeficiency virus,
      and chronic renal failure were excluded. RESULTS: Between September 1991 and
      December 1998, 2546 anti-HCV positive patients were identified of whom 1128 (44%)
      were enrolled in the cohort. A risk factor(s) for infection was identified in
      93.4% of patients who completed the questionnaire; 81% of patients were HCV RNA
      positive. A total of 397 initial liver biopsies were scored by a single
      pathologist. These showed a correlation between high alcohol intake and fibrosis
      score. Multivariate analysis showed fibrosis to be associated with age over 40,
      past evidence of hepatitis B virus infection, and higher necroinflammatory grade
      but not with sex, viral genotype, maximum known alcohol intake, estimated
      duration of infection, or mode of transmission. Twelve (7.8%) of 153 patients who
      received interferon therapy had sustained serum virus clearance. Sixty six
      patients have died during the follow up period, 31 with a liver related cause of
      death. This represents a considerable excess over the expected death rate for a
      cohort of this age and sex distribution. CONCLUSIONS: HCV infection is an
      emerging health problem in the Trent region. Identifying risk factors for
      infection and disease severity will enhance understanding and facilitate improved
      intervention. An excess mortality in infected individuals is already evident in
      this unselected cohort.

PMID- 11302975
TI  - Heterotopic gastric mucosa together with intestinal metaplasia and moderate
      dysplasia in the gall bladder: report of two clinically unusual cases with
      literature review.
AB  - We report the clinicopathological findings of two patients with ectopic gastric
      mucosa within the gall ladder. The first patient, a 78 year old man, was
      asymptomatic. He was admitted to hospital for a colon adenocarcinoma.
      Intraoperatively, a firm nodule was palpable in the gall bladder. Histological
      examination of the resected specimen revealed a body type gastric mucosa in the
      submucosa, adjacent to which were extensive pyloric gland and intestinal
      metaplasia with mild to moderate dysplasia. The remaining gall bladder mucosa
      demonstrated changes of chronic cholecystitis. The second patient was a 62 year
      old woman with symptoms of chronic cholecystitis. The preoperative diagnosis was
      consistent with this diagnosis with a "polyp" at the junction of the neck and
      cystic duct. Cholecystectomy was performed and the histological examination of
      the resected specimen showed that the "polyp" consisted of heterotopic gastric
      mucosa with glands of body and fundus type. In the remaining mucosa, chronic
      cholecystitis was evident. To the best of our knowledge, this is the first report
      of a clinicopathological presentation of heterotopic gastric mucosa, pyloric
      gland type, and intestinal metaplasia with dysplastic changes in the gall
      bladder. As heterotopic tissue may promote carcinogenesis of the gall bladder,
      close attention should be paid to any occurrence of such lesions in this
      anatomical region.

PMID- 11302974
TI  - Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver
      disease.
AB  - Hepatitis C virus (HCV) infection becomes chronic in more than 70% of patients,
      leading to end stage liver disease in about 20-30% of these patients. Apart from
      the virus itself, host factors that modulate the immune response are likely to be
      involved in determining the outcome of HCV infection. Studies on the association
      of human leucocyte antigens (HLAs) and HCV infection have shown inconsistent
      results. Selection of patient subgroups may be crucial. However, any association
      relevant to HCV disease progression will become evident, especially in those
      patients with end stage liver disease. Therefore, we analysed the phenotype
      frequencies of HLA antigens in two groups of 69 and 39 patients with HCV induced
      liver cirrhosis who had received a transplant or were awaiting liver
      transplantation. The first group was typed serologically and compared with 331
      blood and liver donors. The second group, prospectively HLA typed by a polymerase
      chain reaction-sequence specific oligonucleotide (PCR-SSO) procedure for HLA-DRB
      and DQB alleles, was compared with another 170 PCR-SSO typed and randomly
      selected blood donors. Decreased frequencies for HLA-DR5 and HLA-DQ3 were found
      in one group of patients with HCV induced liver cirrhosis compared with the
      control groups. In the second analysis comparing 39 patients with end stage liver
      cirrhosis with blood donors, we confirmed the significant decrease in HLA-DRB1*11
      and HLA-DQB1*03, which corresponded to serological HLA-DR5 and HLA-DQ3 antigens,
      respectively. Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03
      alleles is associated with a reduced risk for the development of HCV induced end
      stage liver disease.

PMID- 11302976
TI  - Distinct outcomes of chloride diarrhoea in two siblings with identical genetic
      background of the disease: implications for early diagnosis and treatment.
AB  - BACKGROUND: Congenital chloride diarrhoea (CLD, OMIM 214700) is a serious
      inherited defect of intestinal electrolyte absorption transmitted in an autosomal
      recessive fashion. The major clinical manifestation is diarrhoea with high
      chloride content which can be balanced by substitution. The molecular pathology
      involves an epithelial Cl(-)/HCO(3)(-) exchanger protein, encoded by the solute
      carrier family 26, member 3 gene (SLC26A3), previously known as CLD or DRA
      (downregulated in adenomas). To date, almost 30 different mutations in the
      SLC26A3 gene have been identified throughout the world. No clear genotype
      phenotype correlation has been established. PATIENTS/METHODS: Two siblings
      presenting with CLD were studied for disease history, supplementation, or other
      treatments, and for mutations in the SLC26A3 gene. RESULTS: Mutation analysis
      revealed a homozygous I544N mutation in both patients. However, despite the
      uniform genetic background of CLD in this family, the clinical picture and
      outcome of the disease were remarkably different between siblings. The older
      sibling had a late diagnosis and chronic course of the disease whereas the
      younger one, who was diagnosed soon after birth and immediately received
      supplementation therapy, grows and develops normally. CONCLUSION: Time of
      diagnosis, substitution therapy, compliance, and compensatory mechanisms are more
      important modulators of the clinical picture of CLD than the type of mutation in
      the SLC26A3 gene.

PMID- 11302977
TI  - A winking anus may signify spinal injury.

PMID- 11302978
TI  - Persistent low prevalence of Western digestive diseases in Africa: confounding
      aetiological factors.

PMID- 11302983
TI  - National Institute for Clinical Excellence guidance: too NICE to glycoprotein
      IIb/IIIa inhibitors?

PMID- 11302979
TI  - The promise and potential hazards of adenovirus gene therapy.

PMID- 11302984
TI  - Sinus of Valsalva aneurysm rupture into the left atrium.

PMID- 11302985
TI  - Pulse pressure and prognosis.

PMID- 11302986
TI  - A "new" coronary anomaly: origin of the right coronary artery below the aortic
      valve.

PMID- 11302987
TI  - Predicting and reducing cardiovascular risk.

PMID- 11302988
TI  - Methods for the prediction of coronary heart disease risk.

PMID- 11302989
TI  - Absolute, attributable, and relative risk in the management of coronary heart
      disease.

PMID- 11302990
TI  - Right aortic arch and coarctation: delineation by three dimensional magnetic
      resonance angiogram.

PMID- 11302991
TI  - Management of pregnancy in women with congenital heart disease.

PMID- 11302992
TI  - Glucose, insulin, and the cardiovascular system.

PMID- 11302993
TI  - Giant aneurysm of the right coronary artery presenting with a systolic murmur.

PMID- 11302995
TI  - Double orifice mitral valve associated with non-compaction of left ventricle.

PMID- 11302996
TI  - Non-cardiac surgery in the heart failure patient.

PMID- 11302994
TI  - The fate of acute myocarditis between spontaneous improvement and evolution to
      dilated cardiomyopathy: a review.

PMID- 11302997
TI  - Metastatic cardiac squamous cell carcinoma arising in the left ventricle.

PMID- 11302998
TI  - Beneficial haemodynamic effects of insulin in chronic heart failure.
AB  - OBJECTIVE: To characterise the central and regional haemodynamic effects of
      insulin in patients with chronic heart failure. DESIGN: Single blind, placebo
      controlled study. SETTING: University teaching hospital. PATIENTS: Ten patients
      with stable chronic heart failure. INTERVENTIONS: Hyperinsulinaemic euglycaemic
      clamp and non-invasive haemodynamic measurements. MAIN OUTCOME MEASURES: Change
      in resting heart rate, blood pressure, cardiac output, and regional splanchnic
      and skeletal muscle blood flow. RESULTS: Insulin infusion led to a dose dependent
      increase in skeletal muscle blood flow of 0.36 (0.13) and 0.73 (0.14) ml/dl/min
      during low and high dose insulin infusions (p < 0.05 and p < 0.005 v placebo,
      respectively). Low and high dose insulin infusions led to a fall in heart rate of
      4.6 (1.4) and 5.1 (1.3) beats/min (p < 0.05 and p < 0.005 v placebo,
      respectively) and a modest increase in cardiac output. There was no significant
      change in superior mesenteric artery blood flow. CONCLUSION: In patients with
      chronic heart failure insulin is a selective skeletal muscle vasodilator that
      leads to increased muscle perfusion primarily through redistribution of regional
      blood flow rather than by increased cardiac output. These results provide a
      rational haemodynamic explanation for the apparent beneficial effects of insulin
      infusion in the setting of heart failure.

PMID- 11302999
TI  - Acute mitral valve dysfunction: a new case of leaflet escape.

PMID- 11303001
TI  - Acute thrombotic occlusion of the right coronary artery treated successfully with
      a helical thrombectomy device.

PMID- 11303000
TI  - Three dimensional echocardiography documents haemodynamic improvement by
      biventricular pacing in patients with severe heart failure.
AB  - OBJECTIVES: To quantify the short term haemodynamic effects of biventricular
      pacing in patients with heart failure and left bundle branch block by using three
      dimensional echocardiography. DESIGN: Three dimensional echocardiography was
      performed in 15 consecutive heart failure patients (New York Heart Association
      functional class III or IV) with an implanted biventricular pacing system. Six
      minute walk tests were performed to investigate the effect of biventricular
      pacing on exercise capacity. Data were acquired at sinus rhythm and after short
      term (2-7 days) biventricular pacing. RESULTS: Compared with baseline values,
      biventricular pacing significantly reduced left ventricular end diastolic volume
      (EDV) by mean (SD) 4.0 (5.1)% (p < 0.01) and end systolic volume (ESV) by 5.6
      (6.4)% (p < 0.02). Mitral regurgitant fraction was significantly reduced by 11
      (12.1)% (p < 0.003) and forward stroke volume (FSV) increased by 13.9 (18.6)% (p
      < 0.02). Exercise capacity was significantly improved with biventricular pacing
      by 48.4 (43.3)% (p < 0.00001). Regression analyses showed that the percentage
      increase in FSV independently predicted percentage improvement in walking
      distance (r(2) = 0.73, p < 0.0002). Both basal QRS duration and QRS narrowing
      predicted pacing efficacy, showing a significant correlation with %DeltaEDV,
      %DeltaESV, and %DeltaFSV. CONCLUSIONS: In five of 15 consecutive patients with
      heart failure and left bundle branch block, biventricular pacing induced a more
      than 15% increase in FSV, which predicted a more than 25% increase in walking
      distance and was accompanied by an immediate reduction in left ventricular
      chamber size and mitral regurgitation.

PMID- 11303003
TI  - Multiple penetrating atherosclerotic ulcers of the abdominal aorta: treatment by
      endovascular stent graft placement.

PMID- 11303002
TI  - Full recovery of contraction late after acute myocardial infarction: determinants
      and early predictors.
AB  - OBJECTIVES: To assess the relative value of electrocardiographic,
      echocardiographic, angiographic, and in-hospital therapeutic indices for
      predicting late functional recovery after acute myocardial infarction, and to
      determine the variables associated with absence of recovery, partial recovery,
      and full recovery. DESIGN: Prospective observational follow up study. SETTING:
      Teaching hospital. PATIENTS: 74 consecutive patients with a first uncomplicated
      acute myocardial infarct. INTERVENTIONS: Dobutamine-atropine stress
      echocardiography was performed mean (SD) 5 (2) days after the acute event.
      Quantitative angiography was available in all patients before hospital discharge.
      A follow up resting echocardiogram was obtained 12 (2) months later. RESULTS:
      Functional recovery (partial, n = 18; full, n = 27) was observed in 45 of the 74
      patients. Recovery was associated with earlier thrombolytic treatment (p =
      0.008), earlier peak concentration of creatine kinase (p = 0.009), greater
      contractile reserve (p = 0.0001), non-Q wave acute myocardial infarction (p =
      0.002), and more frequent elective angioplasty of the infarct related vessel (p =
      0.0004). Three independent variables were selected stepwise from multivariate
      analysis for predicting late recovery: contractile reserve (chi(2) = 24.2, p <
      0.0001); non-Q wave infarction (chi(2) = 15.7, p = 0.0001); and the time from
      symptom onset to thrombolysis (chi(2) = 4.94, p = 0.026). Three independent
      variables predicted full recovery: contractile reserve (chi(2) = 17.2, p =
      0.0001); non-Q wave infarction (chi(2) = 10.1, p = 0.0016); and elective
      angioplasty of the infarct related artery (chi(2) = 4.53, p = 0.033). Only
      contractile reserve (chi(2) = 17.0, p < 0.001) was selected from the multivariate
      analysis for its ability to distinguish between partial recovery and absence of
      recovery. CONCLUSIONS: Late recovery of contraction relates to earlier treatment,
      which is associated with lower infarct size unmasked by a non-Q wave event and
      the presence of contractile reserve. Elective coronary angioplasty of the infarct
      related artery before hospital discharge is associated with full recovery.

PMID- 11303004
TI  - Short early filling deceleration time on day 1 after acute myocardial infarction
      is associated with short and long term left ventricular remodelling.
AB  - OBJECTIVE: To assess the relations between early filling deceleration time, left
      ventricular remodelling, and cardiac mortality in an unselected group of
      postinfarction patients. DESIGN AND PATIENTS: Prospective evaluation of 131
      consecutive patients with first acute myocardial infarction. Echocardiography was
      performed on day 1, day 2, day 3, day 7, at three and six weeks, and at three,
      six, and 12 months after infarction. According to deceleration time on day 1,
      patients were divided into groups with short (< 150 ms) and normal deceleration
      time (>/= 150 ms). SETTING: Tertiary care centre. RESULTS: Patients with a short
      deceleration time had higher end systolic and end diastolic volume indices and a
      higher wall motion score index, but a lower ejection fraction, in the year after
      infarction. These patients also showed a significant increase in end diastolic (p
      < 0.001) and end systolic volume indices (p = 0.007) during the follow up period,
      while ejection fraction and wall motion score index remained unchanged. In the
      group with normal deceleration time, end diastolic volume index increased (p <
      0.001) but end systolic volume index did not change; in addition, the ejection
      fraction increased (p = 0.002) and the wall motion score index decreased (p <
      0.001). One year and five year survival analysis showed greater cardiac mortality
      in patients with a short deceleration time (p = 0.04 and p = 0.02, respectively).
      In a Cox model, which included initial ejection fraction, infarct location, and
      infarct size, deceleration time on day 1 was the only significant predictor of
      five year mortality. CONCLUSIONS: A short deceleration time on day 1 after acute
      myocardial infarction can identify patients who are likely to undergo left
      ventricular remodelling in the following year. These patients have a higher one
      year and five year cardiac mortality.

PMID- 11303005
TI  - A cardiac prevention and rehabilitation programme for all patients at first
      presentation with coronary artery disease.
AB  - OBJECTIVE: To develop and test a cardiac prevention and rehabilitation programme
      for achieving sustained lifestyle, risk factor, and therapeutic targets in
      patients presenting for the first time with exertional angina, acute coronary
      syndromes, or coronary revascularisation. DESIGN: A descriptive study. SETTING: A
      hospital based 12 week outpatient programme. INTERVENTIONS: A multiprofessional
      family based programme of lifestyle and risk factor modification. MAIN OUTCOME
      MEASURES: Non-smoking status, body mass index, blood pressure, plasma
      cholesterol, use of prophylactic drugs. RESULTS: 158 patients (82% of 194
      possible cases) were recruited over 15 months, with 72% completing the programme.
      Targets for achieving non-smoking status, blood pressure < 140/90 mm Hg, and
      total cholesterol < 4.8 mmol/l were achieved in 92%, 73%, and 62%, respectively,
      and the proportion on aspirin, beta blockers, and lipid lowering treatment was
      95%, 58%, and 64% on referral back to general practice for continuing care.
      CONCLUSIONS: A comprehensive cardiac prevention and rehabilitation programme can
      be offered to all patients presenting for the first time with coronary heart
      disease, including those with exertional angina who are normally managed in
      primary care. Lifestyle, risk factor, and therapeutic targets can be successfully
      achieved in most patients with such a hospital based programme.

PMID- 11303006
TI  - Cost effectiveness of ramipril treatment for cardiovascular risk reduction.
AB  - OBJECTIVE: To assess the cost effectiveness of ramipril treatment in patients at
      low, medium, and high risk of cardiovascular death. DESIGN: Population based cost
      effectiveness analysis from the perspective of the health care provider in the
      UK. Effectiveness was modelled using data from the HOPE (heart outcome prevention
      evaluation) trial. The life table method was used to predict mortality in a
      medium risk cohort, as in the HOPE trial (2.44% annual mortality), and in low and
      high risk groups (1% and 4.5% annual mortality, respectively). SETTING: UK
      population using 1998 government actuary department data. MAIN OUTCOME MEASURE:
      Cost per life year gained at five years and lifetime treatment with ramipril.
      RESULTS: Cost effectiveness was pound36 600, pound13 600, and pound4000 per life
      year gained at five years and pound5300, pound1900, and pound100 per life year
      gained at 20 years (lifetime treatment) in low, medium, and high risk groups,
      respectively. Cost effectiveness at 20 years remained well below that of
      haemodialysis ( pound25 000 per life year gained) over a range of potential drug
      costs and savings. Treatment of the HOPE population would cost the UK National
      Health Service (NHS) an additional pound360 million but would prevent 12 000
      deaths per annum. CONCLUSIONS: Ramipril is cost effective treatment for
      cardiovascular risk reduction in patients at medium, high, and low pretreatment
      risk, with a cost effectiveness comparable with the use of statins.
      Implementation of ramipril treatment in a medium risk population would result in
      a major reduction in cardiovascular deaths but would increase annual NHS spending
      by pound360 million.

PMID- 11303007
TI  - An omega-3 polyunsaturated fatty acid concentrate administered for one year
      decreased triglycerides in simvastatin treated patients with coronary heart
      disease and persisting hypertriglyceridaemia.
AB  - BACKGROUND: Omega-3 fatty acids, such as those present in fish oil, have been
      reported to prolong life in myocardial infarction survivors. These fatty acids
      can decrease serum triglyceride concentrations, but so far the doses used in
      trials examining their effects on coronary end points have had only minimal
      triglyceride lowering effects. OBJECTIVE: To examine the triglyceride lowering
      effectiveness, safety, and tolerability of Omacor, a concentrate of omega-3, long
      chain, polyunsaturated fatty acids from fish oil (84% of the total as opposed to
      an average of 35% in fish oil) over one year in patients with established
      coronary heart disease (CHD) and persisting hypertriglyceridaemia, despite
      receiving simvastatin in doses similar to those employed in the Scandinavian
      simvastatin survival study. SUBJECTS AND METHODS: 59 patients with CHD, receiving
      simvastatin 10-40 mg daily with serum triglycerides > 2.3 mmol/l, were randomised
      to receive Omacor 2 g twice a day or placebo for 24 weeks in a double blind
      trial. Forty six patients accepted the offer of active treatment for a further 24
      weeks in an open phase of the trial. RESULTS: There was a sustained significant
      decrease in serum triglycerides by 20-30% (p < 0.005) and in very low density
      lipoprotein (VLDL) cholesterol by 30-40% (p < 0.005) in patients receiving active
      Omacor at three, six, and 12 months compared either to baseline or placebo.
      Omacor did not have any deleterious effect on low density or high density
      lipoprotein cholesterol or on biochemical and haematological safety tests. There
      was no adverse effect on glycaemic control in patients with diabetes, who showed
      a decrease in serum triglyceride, which was at least as great as in non-diabetic
      patients. One patient receiving placebo died of acute myocardial infarction.
      Three patients withdrew from the trial (two on placebo and one on active
      treatment). Omacor was generally well tolerated. CONCLUSION: Omacor was found to
      be a safe and effective means of lowering serum triglycerides over one year in
      patients with CHD and combined hyperlipidaemia, whose triglycerides remained
      elevated despite simvastatin treatment.

PMID- 11303009
TI  - Bilateral ostial coronary artery stenoses: an important presentation of
      Takayasu's arteritis.

PMID- 11303008
TI  - Effect of power Doppler and digital subtraction techniques on the comparison of
      myocardial contrast echocardiography with SPECT.
AB  - OBJECTIVE: To compare the accuracy and feasibility of harmonic power Doppler and
      digitally subtracted colour coded grey scale imaging for the assessment of
      perfusion defect severity by single photon emission computed tomography (SPECT)
      in an unselected group of patients. DESIGN: Cohort study. SETTING: Regional
      cardiothoracic unit. PATIENTS: 49 patients (mean (SD) age 61 (11) years; 27
      women, 22 men) with known or suspected coronary artery disease were studied with
      simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole
      stress. MAIN OUTCOME MEASURES: Regional myocardial perfusion by SPECT, performed
      with (99m)Tc tetrafosmin, scored qualitatively and also quantitated as per cent
      maximum activity. RESULTS: Normal perfusion was identified by SPECT in 225 of 270
      segments (83%). Contrast echo images were interpretable in 92% of patients. The
      proportion of normal MCE by grey scale, subtracted, and power Doppler techniques
      were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts,
      compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique,
      specificity was lowest in the lateral wall, although power Doppler was the least
      affected. Grey scale and subtraction techniques were least accurate in the septal
      wall, but power Doppler showed particular problems in the apex. On a per patient
      analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery
      disease using grey scale, colour coded, and power Doppler, respectively, with a
      significant difference between power Doppler and grey scale only (p < 0.05).
      Specificity was also the highest for power Doppler, at 55%, but not significantly
      different from subtracted colour coded images. CONCLUSIONS: Myocardial contrast
      echo using harmonic power Doppler has greater accuracy than with grey scale
      imaging and digital subtraction. However, power Doppler appears to be less
      sensitive for mild perfusion defects.

PMID- 11303010
TI  - Clinical outcome following coronary angioplasty in dialysis patients: a case
      control study in the era of coronary stenting.
AB  - BACKGROUND: Balloon coronary angioplasty has been reported to be ineffective in
      patients treated for end stage renal disease because of a high restenosis rate.
      OBJECTIVE: To compare the clinical outcome following coronary angioplasty with
      provisional stenting in dialysis versus non-dialysis patients. DESIGN: A case
      control study. PATIENTS: Of 1428 consecutive patients who underwent coronary
      angioplasty, 100 (7%) were being treated for end stage renal disease. These were
      compared with 100 control patients matched for age, sex, coronary lesions,
      presence of diabetes mellitus, and rate of coronary stenting (40%). MAIN OUTCOME
      MEASURES: In-hospital and one year clinical outcome. RESULTS: The rates of
      procedural success (90% v 93%), in-hospital mortality (1% v 0%), stent thrombosis
      (0% v 0%), and Q wave myocardial infarction (0% v 1%) were similar in dialysis
      and non-dialysis patients. One year clinical outcome after coronary angioplasty
      was similar in the two groups in terms of clinical restenosis (31% v 28%) and
      myocardial infarction (6% v 2%), but cardiac death was more common in dialysed
      patients (11% v 2%, p < 0.03). CONCLUSIONS: Dialysis does not increase the risk
      of clinical restenosis after coronary angioplasty with provisional stenting.
      Coronary angioplasty is a safe and effective therapeutic procedure in selected
      dialysis patients with culprit lesions accessible to stenting. However, the one
      year survival is reduced in this high risk population.

PMID- 11303012
TI  - Correlation between high frequency intravascular ultrasound and histomorphology
      in human coronary arteries.
AB  - OBJECTIVE: To test the efficacy of high frequency intravascular ultrasound (IVUS)
      transducers in identifying lipid/necrotic pools in atherosclerotic plaques.
      METHODS: 40 MHz transducers were used for in vitro IVUS assessment of 12 arterial
      segments (10 coronary and two carotid arteries, dissected from five different
      necropsy cases). IVUS acquisition was performed at 0.5 mm/s after ligature of the
      branching points to generate a closed system. Lipid/necrotic areas were defined
      by IVUS as large echolucent intraplaque areas surrounded by tissue with higher
      echodensity. To obtain histopathological sections corresponding to IVUS cross
      sections, vessels were divided into consecutive 3 mm long segments using the most
      distal recorded IVUS image as the starting reference. Samples were then fixed
      with 10% buffered formalin, processed for histopathological study, serially cut,
      and stained using the Movat pentacrome method. RESULTS: 122 sections were
      analysed. Lipid pools were observed by histology in 30 sections (25%). IVUS
      revealed the presence of lipid pools in 19 of these sections (16%; sensitivity
      65%, specificity 95%). CONCLUSIONS: In vitro assessment of lipid/necrotic pools
      with high frequency transducers was achieved with good accuracy. This opens new
      perspectives for future IVUS characterisation of atherosclerotic plaques.

PMID- 11303011
TI  - Endovascular stents in the management of coarctation of the aorta in the
      adolescent and adult: one year follow up.
AB  - OBJECTIVES: To test the hypothesis that endovascular stents used with dilation of
      coarctation of the aorta (CoA) improve late outcomes. Balloon dilation for CoA
      has been limited by concerns over the risk for acute dissection, late restenosis,
      or aneurysm formation. DESIGN: All patients seen with CoA between November 1994
      and September 1997 underwent attempted stent implantation. Follow up was obtained
      for all patients and a subgroup (n = 18) had repeat catheterisation at a mean
      (SD) of 1.3 (0.5) years to assess residual gradient and stent-CoA morphology.
      RESULTS: Stents were placed in 27 patients (15 male and 12 female patients, mean
      age 30.1 (13.1) years), of whom seven had prior surgical coarctectomy and one had
      a prior balloon dilation. Hypertension was present in 26 patients (mean pressure
      164 (26)/86 (13) mm Hg), of whom 16 were on antihypertension drugs. CoA gradients
      were 46 (20) mm Hg (range 18-106 mm Hg) at baseline and 3 (5) mm Hg after the
      procedure. One patient had a stroke following the procedure; another patient had
      incomplete dilation and underwent a second procedure. At 1.8 (1) years after the
      procedure the mean pressure was 130 (14)/74 (11) mm Hg with seven patients on
      antihypertension treatment. The clinical gradient was 4 (8) mm Hg (range 0-32 mm
      Hg). At follow up angiography, the mean gradient was 4(6) mm Hg, and two patients
      had a gradient over 10 mm Hg. Aneurysms formed in three patients at the dilation
      site; one patient was referred for surgery. CONCLUSION: In this age group stent
      management for CoA appears to be an effective technique and results in sustained
      reduction in CoA gradients at early term follow up, but aortic aneurysm was
      detected in 17% of patients who had repeat angiography.

PMID- 11303013
TI  - Increased concentrations of inflammatory mediators in unstable angina:
      correlation with serum troponin T.
AB  - OBJECTIVE: To measure plasma interferon gamma, monocyte chemotactic protein-1
      (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin
      T in unstable angina. DESIGN: Blood sampling in patients undergoing coronary
      arteriography for known or suspected ischaemic heart disease. PATIENTS: 76
      patients divided in three groups: 29 with unstable angina (group 1), 28 with
      stable angina (group 2), and 19 without ischaemic heart disease and with
      angiographically normal coronary arteries (group 3). MAIN OUTCOME MEASURES:
      Plasma interleukin 6, interferon gamma, MCP-1, and troponin T in the three groups
      of patients. RESULTS: Interleukin 6 was increased in group 1 (median 2.19 (range
      0.53-50.84) pg/ml) compared with the control group (1.62 (0.79-3.98) pg/ml) (p <
      0.005), whereas interferon gamma was higher in group 1 (range 0-5.51 pg/ml) than
      in the other two groups (range 0-0.74 pg/ml and 0-0.37 pg/ml; p < 0.005 and p <
      0.001, respectively). Patients with unstable angina (group 1) and positive
      troponin T had higher concentrations of interferon gamma than those with negative
      troponin T (0-5.51 pg/ml v 0-0.60 pg/ml, p < 0.001). Plasma MCP-1 was also higher
      in group 1 (median 267 (range 6-8670) pg/ml) than in the other two groups (134
      (19-890) pg/ml and 84.5 (5-325) pg/ml; p < 0.005 and p < 0.001, respectively),
      and among group 1 patients with a positive troponin T assay than in those with
      normal troponin T (531 (14.5-8670) pg/ml v 69 (6-3333) pg/ml; p < 0.01). There
      was no difference in plasma interleukin 6 in group 1 patients between those with
      and without raised troponin T. CONCLUSIONS: The inflammatory cytokines interferon
      gamma and MCP-1 are increased in patients with unstable angina, particularly in
      those with raised concentrations of troponin T, suggesting that they are probably
      related to myocardial cell damage or to plaque rupture and thrombus formation.

PMID- 11303014
TI  - Acute pressure overload cardiac arrhythmias are dependent on the presence of
      myocardial tissue catecholamines.

PMID- 11303015
TI  - Non-invasive characterisation of coronary lesion morphology by multi-slice
      computed tomography: a promising new technology for risk stratification of
      patients with coronary artery disease.

PMID- 11303016
TI  - Effects of pretreatment with verapamil on early recurrences after electrical
      cardioversion of persistent atrial fibrillation: a randomised study.

PMID- 11303017
TI  - Cardiovascular magnetic resonance.

PMID- 11303018
TI  - Prosthetic valve endocarditis.

PMID- 11303019
TI  - Radiofrequency catheter ablation of supraventricular arrhythmias.

PMID- 11303020
TI  - Modulation of ATP-sensitive potassium channels by cGMP-dependent protein kinase
      in rabbit ventricular myocytes.
AB  - This investigation used a patch clamp technique to test the hypothesis that
      protein kinase G (PKG) contributes to the phosphorylation and activation of ATP
      sensitive K(+) (K(ATP)) channels in rabbit ventricular myocytes. Nitric oxide
      donors and PKG activators facilitated pinacidil-induced K(ATP) channel activities
      in a concentration-dependent manner, and a selective PKG inhibitor abrogated
      these effects. In contrast, neither a selective protein kinase A (PKA) activator
      nor inhibitor had any effect on K(ATP) channels at concentrations up to 100 and
      10 microm, respectively. Exogenous PKG, in the presence of both cGMP and ATP,
      increased channel activity, while the catalytic subunit of PKA had no effect. PKG
      activity was prevented by heat inactivation, replacing ATP with adenosine 5'-O
      (thiotriphosphate) (a nonhydrolyzable analog of ATP), removing Mg(2+) from the
      internal solution, applying a PKG inhibitor, or by adding exogenous protein
      phosphatase 2A. The effects of cGMP analogs and PKG were observed under
      conditions in which PKA was repressed by a selective PKA inhibitor. The results
      suggest that K(ATP) channels are regulated by a PKG-signaling pathway that acts
      via PKG-dependent phosphorylation. This mechanism may, at least in part,
      contribute to a signaling pathway that induces ischemic preconditioning in rabbit
      ventricular myocytes.

PMID- 11303021
TI  - Characterization of a G protein-activated phosphoinositide 3-kinase in vascular
      smooth muscle cell nuclei.
AB  - Recent studies highlight the existence of an autonomous nuclear
      polyphosphoinositide metabolism related to cellular proliferation and
      differentiation. However, only few data document the nuclear production of the
      putative second messengers, the 3-phosphorylated phosphoinositides, by the
      phosphoinositide 3-kinase (PI3K). In the present paper, we examine whether GTP
      binding proteins can directly modulate 3-phosphorylated phosphoinositide
      metabolism in membrane-free nuclei isolated from pig aorta smooth muscle cells
      (VSMCs). In vitro PI3K assays performed without the addition of any exogenous
      substrates revealed that guanosine 5'-(gamma-thio)triphosphate (GTPgammaS)
      specifically stimulated the nuclear synthesis of phosphatidylinositol 3,4,5
      trisphosphate (PtdIns(3,4,5)P(3)), whereas guanosine 5'-(beta-thio)diphosphate
      was ineffective. PI3K inhibitors wortmannin and LY294002 prevented GTPgammaS
      induced PtdIns(3,4,5)P(3) synthesis. Moreover, pertussis toxin inhibited
      partially PtdIns(3,4,5)P(3) accumulation, suggesting that nuclear G(i)/G(0)
      proteins are involved in the activation of PI3K. Immunoblot experiments showed
      the presence of Galpha(0) proteins in VSMC nuclei. In contrast with previous
      reports, immunoblots and indirect immunofluorescence failed to detect the
      p85alpha subunit of the heterodimeric PI3K within VSMC nuclei. By contrast, we
      have detected the presence of a 117-kDa protein immunologically related to the
      PI3Kgamma. These results indicate the existence of a G protein-activated PI3K
      inside VSMC nucleus that might be involved in the control of VSMC proliferation
      and in the pathogenesis of vascular proliferative disorders.

PMID- 11303022
TI  - Demonstration of direct effects of growth hormone on neonatal cardiomyocytes.
AB  - The cellular and molecular basis of growth hormone (GH) actions on the heart
      remain poorly defined, and it is unclear whether GH effects on the myocardium are
      direct or mediated at least in part via insulin-like growth factor (IGF-1). Here,
      we demonstrate that the cultured neonatal cardiomyocyte is not an appropriate
      model to study the effects of GH because of artifactual loss of GH receptors
      (GHRs). To circumvent this problem, rat neonatal cardiomyocytes were infected
      with a recombinant adenovirus expressing the murine GHR. Functional integrity of
      GHR was suggested by GH-induced activation of the cognate JAK2/STAT5, MAPK, and
      Akt intracellular pathways in the cells expressing GHR. Although exposure to GH
      resulted in a significant increase in the size of the cardiomyocyte and increased
      expression of c-fos, myosin light chain 2, and skeletal alpha-actin mRNAs, there
      were no significant changes in IGF-1 or atrial natriuretic factor mRNA levels in
      response to GH stimulation. In this model, GH increased incorporation of leucine,
      uptake of palmitic acid, and abundance of fatty acid transport protein mRNA. In
      contrast, GH decreased uptake of 2-deoxy-d-glucose and levels of Glut1 protein.
      Thus, in isolated rat neonatal cardiomyocytes expressing GHR, GH induces
      hypertrophy and causes alterations in cellular metabolic profile in the absence
      of demonstrable changes in IGF-1 mRNA, suggesting that these effects may be
      independent of IGF-1.

PMID- 11303023
TI  - Differential recruitment of the mammalian mediator subunit TRAP220 by estrogen
      receptors ERalpha and ERbeta.
AB  - Estrogen receptors (ERs) associate with distinct transcriptional coactivators to
      mediate activation of target genes in response to estrogens. Previous work has
      provided multiple evidence for a critical role of p160 coactivators and
      associated histone acetyltransferases in estrogen signaling. In contrast, the
      involvement of the mammalian mediator complex remains to be established. Further,
      although the two subtypes ERalpha and ERbeta appear to be similar in regard to
      principles of LXXLL-mediated coactivator binding to the AF-2 activation domain,
      there are indications that the context-dependent transcriptional activation
      profiles of the two ERs can be quite distinct. Potentially, this could be
      attributed to differences with regard to coregulator recruitment. We have here
      studied the interactions of the nuclear receptor-binding subunit of the mammalian
      mediator complex, referred to as TRAP220, with ERalpha and ERbeta. In comparison
      to the p160 coactivator TIF2, we find that TRAP220 displays ERbeta preference.
      Here, we show that this is a feature of the binding specificity of the TRAP220
      LXXLL motifs and demonstrate that the ER subtype-specific F-domain influences
      TRAP220 interaction. Such differences with regard to coactivator recruitment
      indicate that the relative importance of individual coregulators in estrogen
      signaling could depend on the dominant ER subtype.

PMID- 11303024
TI  - Functional characterization of phosphorylation of 69-kDa human choline
      acetyltransferase at serine 440 by protein kinase C.
AB  - Choline acetyltransferase, the enzyme that synthesizes the transmitter
      acetylcholine in cholinergic neurons, is a substrate for protein kinase C. In the
      present study, we used mass spectrometry to identify serine 440 in recombinant
      human 69-kDa choline acetyltransferase as a protein kinase C phosphorylation
      site, and site-directed mutagenesis to determine that phosphorylation of this
      residue is involved in regulation of the enzyme's catalytic activity and binding
      to subcellular membranes. Incubation of HEK293 cells stably expressing wild-type
      69-kDa choline acetyltransferase with the protein kinase C activator phorbol 12
      myristate 13-acetate showed time- and dose-related increases in specific activity
      of the enzyme; in control and phorbol ester-treated cells, the enzyme was
      distributed predominantly in cytoplasm (about 88%) with the remainder (about 12%)
      bound to cellular membranes. Mutation of serine 440 to alanine resulted in
      localization of the enzyme entirely in cytoplasm, and this was unchanged by
      phorbol ester treatment. Furthermore, activation of mutant enzyme in phorbol
      ester-treated HEK293 cells was about 50% that observed for wild-type enzyme.
      Incubation of immunoaffinity purified wild-type and mutant choline
      acetyltransferase with protein kinase C under phosphorylating conditions led to
      incorporation of [(32)P]phosphate, with radiolabeling of mutant enzyme being
      about one-half that of wild-type, indicating that another residue is
      phosphorylated by protein kinase C. Acetylcholine synthesis in HEK293 cells
      expressing wild-type choline acetyltransferase, but not mutant enzyme, was
      increased by about 17% by phorbol ester treatment.

PMID- 11303025
TI  - Virus-specific activation of a novel interferon regulatory factor, IRF-5, results
      in the induction of distinct interferon alpha genes.
AB  - Interferon regulatory factor (IRF) genes encode DNA-binding proteins that are
      involved in the innate immune response to infection. Two of these proteins, IRF-3
      and IRF-7, serve as direct transducers of virus-mediated signaling and play
      critical roles in the induction of type I interferon genes. We have now shown
      that another factor, IRF-5, participates in the induction of interferon A (IFNA)
      and IFNB genes and can replace the requirement for IRF-7 in the induction of IFNA
      genes. We demonstrate that, despite the functional similarity, IRF-5 possesses
      unique characteristics and does not have a redundant role. Thus, 1) activation of
      IRF-5 by phosphorylation is virus-specific, and its in vivo association with the
      IFNA promoter can be detected only in cells infected with NDV, not Sendai virus,
      while both viruses activate IRF-3 and IRF-7, and 2) NDV infection of IRF-5
      overexpressing cells preferentially induced the IFNA8 subtype, while IFNA1 was
      primarily induced in IRF-7 expressing cells. These data indicate that multiple
      signaling pathways induced by infection may be differentially recognized by
      members of the IRF family and modulate transcription of individual IFNA genes in
      a virus and cell type-specific manner.

PMID- 11303026
TI  - Cytoplasmic domain of natriuretic peptide receptor C constitutes Gi activator
      sequences that inhibit adenylyl cyclase activity.
AB  - We have recently demonstrated that a 37-amino acid peptide corresponding to the
      cytoplasmic domain of the natriuretic peptide receptor C (NPR-C) inhibited
      adenylyl cyclase activity via pertussis toxin (PT)-sensitive G(i) protein. In the
      present studies, we have used seven different peptide fragments of the
      cytoplasmic domain of the NPR-C receptor with complete, partial, or no G(i)
      activator sequence to examine their effects on adenylyl cyclase activity. The
      peptides used were KKYRITIERRNH (peptide 1), RRNHQEESNIGK (peptide 2),
      HRELREDSIRSH (peptide 3), RRNHQEESNIGKHRELR (peptide 4), QEESNIGK (peptide X),
      ITIERRNH (peptide Y), and ITIYKKRRNHRE (peptide Z). Peptides 1, 3, and 4 have
      complete G(i) activator sequences, whereas peptides 2 and Y have partial G(i)
      activator sequences with truncated carboxyl or amino terminus, respectively.
      Peptide X has no structural specificity, whereas peptide Z is the scrambled
      peptide control for peptide 1. Peptides 1, 3, and 4 inhibited adenylyl cyclase
      activity in a concentration-dependent manner with apparent K(i) between 0.1 and 1
      nm; however, peptide 2 inhibited adenylyl cyclase activity with a higher K(i) of
      about 10 nm, and peptides X, Y, and Z were unable to inhibit adenylyl cyclase
      activity. The maximal inhibitions observed were between 30 and 40%. The
      inhibition of adenylyl cyclase activity by peptides 1-4 was absolutely dependent
      on the presence of guanine nucleotides and was completely attenuated by PT
      treatment. In addition, the stimulatory effects of isoproterenol, glucagon, and
      forskolin on adenylyl cyclase activity were inhibited to different degrees by
      these peptides. These results suggest that the small peptide fragments of the
      cytoplasmic domain of the NPR-C receptor containing 12 or 17 amino acids were
      sufficient to inhibit adenylyl cyclase activity through a PT-sensitive G(i)
      protein. The peptides having complete structural specificity of G(i) activator
      sequences at both amino and carboxyl termini were more potent to inhibit adenylyl
      cyclase activity as compared with the peptides having a truncated carboxyl
      terminus, whereas the truncation of the amino-terminal motif completely
      attenuates adenylyl cyclase inhibition.

PMID- 11303027
TI  - ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and
      shared effectors: characterizing ARL1-binding proteins.
AB  - Despite the 40-60% identity between ADP-ribosylation factors (ARFs) and ARF-like
      (ARL) proteins, distinct functional roles have been inferred from findings that
      ARLs lack the biochemical or genetic activities characteristic of ARFs. The
      potential for functional overlap between ARFs and ARLs was examined by comparing
      effects of expression on intact cells and the ability to bind effectors.
      Expression of [Q71L]ARL1 in mammalian cells led to altered Golgi structure
      similar to, but less dramatic than, that reported previously for [Q71L]ARF1. Two
      previously identified partners of ARFs, MKLP1 and Arfaptin2/POR1, also bind ARL1
      but not ARL2 or ARL3. Two-hybrid screens of human cDNA libraries with dominant
      active mutants of human ARL1, ARL2, and ARL3 identified eight different but
      overlapping sets of binding partners. Specific interactions between ARL1 and two
      binding proteins, SCOCO and Golgin-245, are defined and characterized in more
      detail. Like ARFs and ARL1, the binding of SCOCO to Golgi membranes is rapidly
      reversed by brefeldin A, suggesting the presence of a brefeldin A-sensitive ARL1
      exchange factor. These data reveal a complex network of interactions between
      GTPases in the ARF family and their effectors and reveal a potential for cross
      talk not demonstrated previously.

PMID- 11303028
TI  - Translocon pores in the endoplasmic reticulum are permeable to a neutral, polar
      molecule.
AB  - The pore of the translocon complex in the endoplasmic reticulum (ER) is large
      enough to be permeated by small molecules, but it is generally believed that
      permeation is prevented by a barrier at the luminal end of the pore. We tested
      the hypothesis that 4-methylumbelliferyl alpha-d-glucopyranoside (4MalphaG), a
      small, neutral dye molecule, cannot permeate an empty translocon pore by
      measuring its activation by an ER resident alpha-glucosidase, which is dependent
      on entry into the ER. The basal entry of dye into the ER of broken Chinese
      hamster ovary-S cells was remarkably high, and it was increased by the addition
      of puromycin, which purges translocon pores of nascent polypeptides, creating
      additional empty pores. The basal and puromycin-dependent entries of 4MalphaG
      were mediated by a common, salt-sensitive pathway that was partially blocked by
      spermine. A similar activation of 4MalphaG was observed in nystatin-perforated
      cells, indicating that the entry of 4MalphaG into the ER did not result simply
      from the loss of cytosolic factors in broken cells. We reject the hypothesis and
      conclude that a small, neutral molecule can permeate the empty pore of a
      translocon complex, and we propose that translationally inactive, ribosome-bound
      translocons could provide a pathway for small molecules to cross the ER membrane.

PMID- 11303029
TI  - Conformation, recognition by high mobility group domain proteins, and nucleotide
      excision repair of DNA intrastrand cross-links of novel antitumor trinuclear
      platinum complex BBR3464.
AB  - The new antitumor trinuclear platinum compound [(trans-PtCl(NH(3))(2))(2)mu-trans
      Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2)](4+) (designated as BBR3464) is currently
      in phase II clinical trials. DNA is generally considered the major
      pharmacological target of platinum drugs. As such it is of considerable interest
      to understand the patterns of DNA damage. The bifunctional DNA binding of BBR3464
      is characterized by the rapid formation of long range intra- and interstrand
      cross-links. We examined how the structures of the various types of the
      intrastrand cross-links of BBR3464 affect conformational properties of DNA, and
      how these adducts are recognized by high mobility group 1 protein and removed
      from DNA during in vitro nucleotide excision repair reactions. The results have
      revealed that intrastrand cross-links of BBR3464 create a local conformational
      distortion, but none of these cross-links results in a stable curvature. In
      addition, we have observed no recognition of these cross-links by high mobility
      group 1 proteins, but we have observed effective removal of these adducts from
      DNA by nucleotide excision repair. These results suggest that the processing of
      the intrastrand cross-links of BBR3464 in tumor cells sensitive to this drug may
      not be relevant to its antitumor effects. Hence, polynuclear platinum compounds
      apparently represent a novel class of platinum anticancer drugs acting by a
      different mechanism than cisplatin and its analogues.

PMID- 11303030
TI  - Regulation of nuclear localization during signaling.

PMID- 11303031
TI  - Transgenic studies of pain and analgesia: mutation or background genotype?
AB  - The application of transgenic (knockout) technology to the study of pain is
      rapidly expanding. Despite its power, this technique has several shortcomings
      that complicate the interpretation of the data obtained. Although compensation by
      other genes is a well recognized problem, issues related to the background
      genotype of the mutant mice are less well appreciated. This review describes
      these confounds as they apply to studies of pain and pain inhibition. We show
      that the 129 and C57BL/6 mouse strains, which provide the default genetic
      background on which null mutants are constructed, display significant and
      sometimes extreme phenotypic differences in many assays of nociception,
      hypersensitivity, and analgesia. Although problems related to the differential
      responsiveness of the two strains are minimized by placing knockouts onto "pure"
      129 and/or C57BL/6 backgrounds, we also illustrate that neither of these strains
      are particularly representative of inbred mice in general. Procedures to reduce
      confounds and converging evidence must be used to accurately determine the
      functions of the targeted genes in pain-related phenomena.

PMID- 11303032
TI  - Critical role for nitric oxide signaling in cardiac and neuronal ischemic
      preconditioning and tolerance.
AB  - Preconditioning to ischemic tolerance is a phenomenon in which brief episodes of
      a subtoxic insult induce a robust protection against the deleterious effects of
      subsequent, prolonged, lethal ischemia. The subtoxic stimuli that constitute the
      preconditioning event are quite diverse, ranging from brief ischemic episodes,
      spreading depression or potassium depolarization, chemical inhibition of
      oxidative phosphorylation, exposure to excitotoxins and cytokines. The beneficial
      effects of preconditioning were first demonstrated in the heart; it is now clear
      that preconditioning can induce ischemic tolerance in a variety of organ systems
      including brain, heart, liver, small intestine, skeletal muscle, kidney, and
      lung. There are two temporally and mechanistically distinct types of protection
      afforded by preconditioning stimuli, acute and delayed preconditioning. The
      signaling cascades that initiate the acute and delayed preconditioning responses
      may have similar biochemical components. However, the protective effects of acute
      preconditioning are protein synthesis-independent, mediated by post-translational
      protein modifications, and are short-lived. The effects of delayed
      preconditioning require new protein synthesis and are sustained for days to
      weeks. Elucidation of the molecular mechanisms that are involved in
      preconditioning and ischemic tolerance and identification of drugs that mimic
      this protective response have the potential to improve the prognosis of patients
      at risk for ischemic injury. This article focuses on recent findings on the
      effects of ischemic preconditioning in the cardiac and nervous systems and
      discusses potential targets for a successful therapeutic approach to limit
      ischemia-reperfusion injury.

PMID- 11303033
TI  - Cytochrome P450 metabolites of arachidonic acid but not cyclooxygenase-2
      metabolites contribute to the pulmonary vascular hyporeactivity in rats with
      acute Pseudomonas pneumonia.
AB  - We have previously demonstrated depressed vascular contractility in intralobar
      pulmonary artery (PA) rings isolated from rats with acute Pseudomonas pneumonia.
      Here we describe the role of arachidonic acid (AA) metabolites in the regulation
      of pulmonary vascular tone in inflammation. Pneumonia was induced by
      intratracheal injection of P. aeruginosa organisms. Rats were sacrificed 44 h
      later. EETs and 20-HETE were formed at significantly lower rates in pneumonia
      compared with control lung microsomes. Vasoactive effects of CYP metabolites (5,6
      EET, 8,9-EET, 11,12-EET, 14,15-EET, and 20-HETE) on small PA rings from control
      or pneumonia rats were assessed in vitro. All four EETs and 20-HETE were more
      potent PA vasoconstrictors than KCl or phenylephrine (PE). However, this potency
      was attenuated in PA rings from pneumonia lungs compared with control. In
      contrast, pneumonia had no effect on COX activity [total pulmonary prostaglandin
      (PG), PGE(2), and 6-keto-PGF(1 alpha)]. In vitro vascular contractility to KCl,
      PE, or PGF(2 alpha) was assessed in small PA rings from control and pneumonia
      rats in the presence and absence of the COX-2 inhibitor NS-398 (10 microM). NS
      398 did not reverse the attenuated contractile responses to KCl, PE, or PGF(2
      alpha) in pneumonia rats. Nitrite/nitrate levels, inducible nitric-oxide synthase
      and heme oxygenase activities were all significantly elevated in pneumonia lungs.
      In conclusion, vasodilator PGs produced by COX-2 do not contribute to the
      depressed PA contractility in this model of pneumonia. Depressed pulmonary
      production and vasoconstrictor effects of CYP metabolites of AA (possibly due to
      increased NO and/or carbon monoxide) indicate a potential role for these
      vasoactive metabolites in this model of acute pneumonia.

PMID- 11303034
TI  - Characterization of discriminative stimulus effects of the neuroactive steroid
      pregnanolone.
AB  - Reduced pregnane neurosteroids such as allopregnanolone and pregnanolone are
      potent neuromodulators able to affect a number of membrane receptors, including
      gamma-aminobutyric acid (GABA)(A), N-methyl-D-aspartate (NMDA), 5
      hydroxytryptamine (5-HT)(3), and sigma(1) receptors. The present study used a
      drug discrimination procedure to assess further the receptor effects of
      pregnanolone in vivo. Rats were trained to discriminate 5 mg/kg pregnanolone from
      saline in a two-lever operant task maintained by food reinforcement. The opiate
      agonist morphine and the negative GABA(A) modulator dehydroepiandrosterone
      sulfate did not substitute for pregnanolone. All of the GABA(A) positive
      modulators tested (allopregnanolone, epipregnanolone, androsterone,
      pentobarbital, midazolam, and zolpidem) dose dependently substituted for
      pregnanolone. The direct GABA-site agonists 4,5,6,7-tetrahydroisoxazolo[4,5
      c]pyridin-3-ol and muscimol failed to substitute for pregnanolone. Ethanol and
      the sigma(1) receptor agonist SKF 10047 fully substituted for pregnanolone, and
      the NMDA antagonist MK-801 partially substituted for pregnanolone. The 5-HT(3)
      antagonist tropisetron did not substitute at any dose tested. The 5-HT(3) agonist
      SR 57227A reached full substitution, whereas the other 5-HT(3) agonist tested, m
      chlorophenylbiguanide, produced partial substitution. These results suggest that
      positive GABA(A) modulation, but not direct agonism, confers a discriminative
      stimulus effect similar to pregnanolone. Additionally, antagonism of NMDA
      receptors and activation of 5-HT(3) and sigma(1) receptors modulate stimulus
      effects similar to the pregnanolone cue. Overall, the data suggest that
      pregnanolone produces discriminative stimulus effects representative of a wide
      spectrum sedative hypnotic.

PMID- 11303035
TI  - Occupancy of the internal and external pools of glycoprotein IIb/IIIa following
      abciximab bolus and infusion.
AB  - The internal pool of GPIIb/IIIa, which is expressed upon platelet activation, may
      be inaccessible to inhibition by GPIIb/IIIa antagonists. To determine the
      occupancy of the internal and external pools of GPIIb/IIIa and platelet function
      following an abciximab bolus and infusion, 15 patients undergoing elective
      percutaneous transluminal coronary angioplasty were administered abciximab as a
      bolus and 36-h infusion. GPIIb/IIIa receptor number and occupancy in resting and
      TRAP-6 (20 microM)-activated samples (to expose the internal pool of GPIIb/IIIa)
      was quantified using a monoclonal antibody-based assay. Antibody binding was
      quantified by flow cytometry and platelet inhibition by light transmittance
      aggregation and by the rapid platelet function analyser (Accumetrics, San Diego,
      CA). The target of >80% receptor occupancy (range 82--99% occupancy) of the
      external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor
      occupancy of the combined internal and external pools of GPIIb/IIIa was less,
      ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was
      markedly inhibited to 20 microM ADP (maximal, 11 +/- 2% of baseline), but less so
      to 5 microM TRAP-6 (maximal, 36 +/- 25% of baseline). Following discontinuation
      of the drug, there was a gradual fall in receptor occupancy over 15 days
      coinciding with the disappearance of abciximab from the platelet surface. Maximum
      inhibition of platelet function and receptor occupancy of the external pool of
      GPIIb/IIIa occurs within 3 min of an abciximab bolus and infusion. However, some
      internal receptors that are expressed by potent agonists are not occupied, which
      may explain the incomplete inhibition of platelet aggregation.

PMID- 11303036
TI  - Dopamine D1 receptor activation in the medial prefrontal cortex prevents the
      expression of cocaine sensitization.
AB  - This study examined whether microinjection of the full D1 agonist, SKF 81297, or
      the D1 antagonist, SCH 23390, into the medial prefrontal cortex (mPFC) would
      alter the expression phase of cocaine sensitization. Male Sprague-Dawley rats
      were administered saline or cocaine (15 mg/kg, i.p.) once per day for seven
      consecutive days. After 8 to 17 days withdrawal, rats received a bilateral intra
      mPFC microinjection of SKF 81297: either 0, 0.03, 0.1, or 0.3 microg/side; SCH
      23390: either 0, 0.1, 0.3, or 1.0 microg/side; or a combination of 0.1 microg of
      SKF 81297 + 0.3 microg of SCH 23390, followed by an i.p. saline or cocaine (15
      mg/kg, i.p.) injection. In naive rats, vertical activity was elevated by the two
      lower doses of SKF 81297. A similar enhancement of cocaine-induced activity was
      observed in daily saline rats at the highest dose tested. In contrast, SKF 81297
      suppressed the expression of sensitization to cocaine. This blockade of
      sensitization was prevented by coinfusion of SCH 23390. Infusion of SCH 23390
      alone into the mPFC in daily saline and cocaine-pretreated rats demonstrated a
      suppression of cocaine-induced locomotion in daily saline-pretreated rats after
      the highest dose, but a slight augmentation of activity after the lowest dose in
      daily cocaine-pretreated rats. These results demonstrate a contribution by mPFC
      D1 receptors in the expression of cocaine sensitization and further suggest that
      the effects of D1 receptor activation in the mPFC occur in opposite directions in
      daily saline versus daily cocaine-pretreated rats.

PMID- 11303037
TI  - Primaquine-induced hemolytic anemia: formation and hemotoxicity of the
      arylhydroxylamine metabolite 6-methoxy-8-hydroxylaminoquinoline.
AB  - Primaquine is an important antimalarial agent because of its activity against
      exoerythrocytic forms of Plasmodium spp. However, methemoglobinemia and hemolytic
      anemia are dose-limiting side effects of primaquine therapy that limit its
      efficacy. These hemotoxicities are thought to be mediated by metabolites;
      however, the identity of the toxic species has remained unclear. Since N-hydroxy
      metabolites are known to mediate the hemotoxicity of several arylamines, the
      present studies were undertaken to determine whether 6-methoxy-8-aminoquinoline
      (6-MAQ), a known human metabolite of primaquine, could undergo N-hydroxylation to
      form a hemotoxic metabolite. When 6-MAQ was incubated with rat and human liver
      microsomes, a single metabolite was detected by high performance liquid
      chromatography (HPLC) with electrochemical detection. This metabolite was
      identified as 6-methoxy-8-hydroxylaminoquinoline (MAQ-NOH) by HPLC and mass
      spectral analyses. As measured by decreased survival of (51)Cr-labeled
      erythrocytes in rats, MAQ-NOH was hemolytic in vivo. Furthermore, in vitro
      exposure of (51)Cr-labeled erythrocytes to MAQ-NOH caused a concentration
      dependent decrease in erythrocyte survival (EC(50) of 350 microM) when the
      exposed cells were returned to the circulation of isologous rats. MAQ-NOH also
      induced the formation of methemoglobin when incubated with suspensions of rat
      erythrocytes. These data indicate that 6-MAQ can be metabolized to MAQ-NOH by
      both rat and human liver microsomes and that MAQ-NOH has the requisite properties
      to be a hemotoxic metabolite of primaquine. The contribution of MAQ-NOH to the
      hemotoxicity of primaquine in vivo remains to be assessed.

PMID- 11303038
TI  - Effect of stavudine on mitochondrial genome and fatty acid oxidation in lean and
      obese mice.
AB  - Like other antihuman immunodeficiency virus dideoxynucleosides, stavudine may
      occasionally induce lactic acidosis and perhaps lipodystrophy in metabolically or
      genetically susceptible patients. We studied the effects of stavudine on
      mitochondrial DNA (mtDNA), fatty acid oxidation, and blood metabolites in lean
      and genetically obese (ob/ob) mice. In lean mice, mtDNA was depleted in liver and
      skeletal muscle, but not heart and brain, after 6 weeks of stavudine treatment
      (500 mg/kg/day). With 100 mg/kg/day, mtDNA transiently decreased in liver, but
      was unchanged at 6 weeks in all organs, including white adipose tissue (WAT).
      Despite unchanged mtDNA levels, lack of significant oxidative mtDNA lesions (as
      assessed by long polymerase chain reaction experiments), and normal blood
      lactate/pyruvate ratios, lean mice treated with stavudine for 6 weeks had
      increased fasting blood ketone bodies, due to both increased hepatic fatty acid
      beta-oxidation and decreased peripheral ketolysis. In obese mice, basal WAT mtDNA
      was low and was further decreased by stavudine. In conclusion, stavudine can
      decrease hepatic and muscle mtDNA in lean mice and can also cause ketoacidosis
      during fasting without altering mtDNA. Stavudine depletes WAT mtDNA only in obese
      mice. Fasting and ketoacidosis could trigger decompensation in patients with
      incipient lactic acidosis, whereas WAT mtDNA depletion could cause lipodystrophy
      in genetically susceptible patients.

PMID- 11303039
TI  - Comparison of single- versus double-bolus treatments of O(6)-benzylguanine for
      depletion of O(6)-methylguanine DNA methyltransferase (MGMT) activity in vivo:
      development of a novel fluorometric oligonucleotide assay for measurement of MGMT
      activity.
AB  - Previous studies have demonstrated that optimal reversal of 1,3-bis(2
      chloroethyl)-1-nitrosourea (BCNU) resistance requires complete inactivation of
      the DNA repair protein O(6)-methylguanine DNA methyltransferase (MGMT) for at
      least 24 h following BCNU administration. In preparation for clinical trials at
      this institution, this study was undertaken to compare the efficacy of a
      conventional single-bolus dose versus double-bolus dose treatments with O(6)
      benzylguanine (BG) in depleting MGMT activity in vivo. In xenograft human glioma
      SF767 tumors, a single 30-mg/kg bolus dose of BG completely inhibited MGMT
      activity for at least 8 h, but approximately 50% of the basal MGMT activity
      recovered within 24 h. To sustain the MGMT depletion for 24 h, a second bolus
      injection of BG at escalating doses was administered 8 h after the first dose.
      Second bolus doses of 5, 10, and 15 mg/kg BG attenuated the MGMT recovery in a
      dose-dependent manner compared with the single 30-mg/kg BG dose alone. When the
      15-mg/kg BG dose was administered 8 h after the 30-mg/kg initial dose, MGMT
      activity was completely inactivated in the tumor xenografts for 24 h. This double
      bolus BG treatment also depleted MGMT activity in normal murine tissues,
      including the liver, kidney, lung, brain, spleen, and bone marrow; and the
      kinetics of MGMT recovery varied among these tissues. When combined with BCNU
      treatment, the double-bolus BG treatment would be expected to produce greater
      antitumor activity in future trials than the conventional single-bolus BG
      treatment.

PMID- 11303040
TI  - In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12
      hydroxyibogamine (noribogaine), in rats.
AB  - Ibogaine is a naturally occurring compound with purported antiaddictive
      properties. When administered to primates, ibogaine is rapidly o-demethylated to
      form the metabolite 12-hydroxyibogamine (noribogaine). Peak blood levels of
      noribogaine exceed those of ibogaine, and noribogaine persists in the bloodstream
      for at least 1 day. Very few studies have systematically evaluated the
      neurobiological effects of noribogaine in vivo. In the present series of
      experiments, we compared the effects of i.v. administration of ibogaine and
      noribogaine (1 and 10 mg/kg) on motor behaviors, stress hormones, and
      extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus
      accumbens of male rats. Ibogaine caused dose-related increases in tremors,
      whereas noribogaine did not. Both ibogaine and noribogaine produced significant
      elevations in plasma corticosterone and prolactin, but ibogaine was a more potent
      stimulator of corticosterone secretion. Neither drug altered extracellular DA
      levels in the nucleus accumbens. However, both drugs increased extracellular 5-HT
      levels, and noribogaine was more potent in this respect. Results from in vitro
      experiments indicated that ibogaine and noribogaine interact with 5-HT
      transporters to inhibit 5-HT uptake. The present findings demonstrate that
      noribogaine is biologically active and undoubtedly contributes to the in vivo
      pharmacological profile of ibogaine in rats. Noribogaine is approximately 10
      times more potent than ibogaine as an indirect 5-HT agonist. More importantly,
      noribogaine appears less apt to produce the adverse effects associated with
      ibogaine, indicating the metabolite may be a safer alternative for medication
      development.

PMID- 11303041
TI  - Reboxetine modulates the firing pattern of dopamine cells in the ventral
      tegmental area and selectively increases dopamine availability in the prefrontal
      cortex.
AB  - Central dopaminergic neurons have been suggested to be involved in the
      pathophysiology of several psychiatric disorders, including depression, and
      appear to be modulated by noradrenergic activity both at the nerve terminal level
      and at the somatodendritic level. In recent years reboxetine, a selective
      noradrenaline reuptake inhibitor that differs from tricyclic antidepressants by
      its low affinity for muscarinic, cholinergic and alpha(1)-adrenergic receptors,
      has been introduced clinically. In the present study the effect of reboxetine on
      the function of the mesolimbocortical dopamine system was investigated by means
      of single cell recording and microdialysis in rats following administration of
      reboxetine in doses that appear to yield clinically relevant plasma
      concentrations. Reboxetine (0.625--20 mg/kg intravenously) induced an increase in
      burst firing, but not in average firing frequency of dopamine (DA) cells in the
      ventral tegmental area (VTA). Moreover, reboxetine (0.15--13.5 mg/kg
      intraperitoneally) caused a significantly enhanced DA output in the medial
      prefrontal cortex, whereas no effect was observed in the nucleus accumbens. Local
      administration of reboxetine (333 microM, 60 min), by means of reversed
      microdialysis into these brain regions, caused a significant increase in DA
      output in both brain regions. However, local administration of reboxetine into
      the VTA (333 microM, 60 min) did not affect DA availability in these terminal
      areas. Our results imply that clinical treatment with reboxetine may result in
      facilitation of both prefrontal DA output and the excitability of VTA DA neurons,
      effects that may contribute to its antidepressant action, especially on drive and
      motivation.

PMID- 11303042
TI  - Contribution of P-glycoprotein to the enhancing effects of dimethyl-beta
      cyclodextrin on oral bioavailability of tacrolimus.
AB  - We recently reported that of all hydrophilic cyclodextrin (CyD) derivatives
      examined, 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD) most significantly
      increased the aqueous solubility and the dissolution rate, resulting in the
      improvement of oral bioavailability of the immunosuppressive drug tacrolimus in
      rats. In the present study, we showed that DM-beta-CyD increased the dissolution
      rate and oral bioavailability of tacrolimus in rats with increases in the molar
      ratio of the complexes (DM-beta-CyD:tacrolimus). However, nonlinear
      pharmacokinetic behavior of tacrolimus after oral administration in rats was
      observed. Thus, an additional mechanism of the solubilizing effect of DM-beta-CyD
      on oral bioavailability of tacrolimus was postulated. To gain insight into this
      additional mechanism of action of DM-beta-CyD, its effects on the efflux of
      tacrolimus and rhodamine 123, a P-glycoprotein (P-gp) substrate, were examined
      using both Caco-2 and vinblastine-resistant Caco-2 (Caco-2R) cell monolayers.
      Pretreatment of the apical membranes of the monolayers with DM-beta-CyD decreased
      the efflux of tacrolimus and rhodamine 123 without an associated cytotoxicity. DM
      beta-CyD decreased the P-gp level in the apical membranes of both Caco-2 and Caco
      2R cell monolayers, probably by allowing release of P-gp from the apical membrane
      into the transport buffer. DM-beta-CyD, however, did not decrease the MDR1 gene
      expression in Caco-2 or Caco-2R cells. These results suggested that the enhancing
      effect of DM-beta-CyD on the oral bioavailability of tacrolimus is due not only
      to its solubilizing effect but also, at least in part, to its inhibitory effect
      on the P-gp-mediated efflux of tacrolimus from intestinal epithelial cells.

PMID- 11303043
TI  - Pharmacokinetics of cocaine in maternal and fetal rhesus monkeys at mid
      gestation.
AB  - We compared pharmacokinetics of cocaine and its metabolite, benzoylecgonine, in
      pregnant rhesus monkeys and their fetuses at mid-gestation: 1) after a single
      intravenous dose of cocaine, 2) after a single oral dose of cocaine, 3) after the
      last oral cocaine administration of a 50-day-long chronic cocaine treatment, and
      4) on the last day of a 50-day-long chronic treatment with five daily intravenous
      cocaine injections. We found that intravenous administrations of cocaine produced
      maximal maternal levels of benzoylecgonine below the plasma levels for cocaine.
      In contrast, oral administrations resulted in the maximal maternal plasma levels
      of this metabolite significantly above those of cocaine. The bioavailability of
      the orally administered cocaine was calculated as 25%. Cocaine was detectable in
      the fetal plasma at maximal levels of approximately 1/5 of peak maternal levels
      for both single intravenous and single oral administrations. The maximal plasma
      levels of benzoylecgonine for the fetuses of the intravenously treated mothers
      were close to those of cocaine, whereas peak levels of this metabolite in the
      plasma of the fetuses of the mothers receiving the oral treatments were above
      those of cocaine. The chronic treatments resulted in significantly higher maximal
      levels of cocaine in the fetal circulation compared with those produced by single
      drug administrations.

PMID- 11303044
TI  - Semicarbazide-sensitive amine oxidase substrates stimulate glucose transport and
      inhibit lipolysis in human adipocytes.
AB  - Semicarbazide-sensitive amine oxidases (SSAO) are widely distributed enzymes
      scavenging biogenic or exogenous amines and generating hydrogen peroxide. We
      asked whether human adipose tissue could express SSAO. Since hydrogen peroxide
      exhibits pharmacological insulin-like effects, we also tested whether its
      endogenous production by SSAO could mimic several insulin effects on adipocytes,
      such as stimulation of glucose uptake and inhibition of lipolysis. The
      benzylamine oxidation by human adipose tissue was inhibited by semicarbazide or
      hydralazine and resistant to pargyline or selegiline. It was due to an SSAO
      activity localized in adipocyte membranes. A protein of 100-kDa and a 4-kb mRNA
      corresponding to SSAO were identified in either mammary or abdominal subcutaneous
      fat depots. In isolated adipocytes, SSAO oxidized similarly benzylamine and
      methylamine that dose dependently stimulated glucose transport in a semicarbazide
      sensitive manner. Antioxidants also inhibited the benzylamine and methylamine
      effects. Moreover, the ability of diverse substrates to be oxidized by adipocytes
      was correlated to their effect on glucose transport. Benzylamine and methylamine
      exerted antilipolytic effects with a maximum attained at 1 mM. These results show
      that human adipocytes express a membrane-bound SSAO that not only readily
      oxidizes exogenous amines and generates H(2)O(2), but that also interplays with
      glucose and lipid metabolism by exerting insulin-like actions. Based on these
      results and the fact that variations in plasma levels of the soluble form of SSAO
      have been previously reported in diabetes, we propose that determination of
      adipocyte SSAO, feasible on subcutaneous microbiopsies, could bring relevant
      information in pathologies such as obesity or diabetes.

PMID- 11303045
TI  - Effect of LY287045, a thrombin/trypsin inhibitor, on thrombin and trypsin-induced
      aortic contraction and relaxation.
AB  - The active site tripeptide arginal inhibitor of thrombin, LY287045, was used to
      study thrombin-induced aortic relaxation and contraction, two responses that
      differ both pharmacologically and physiologically. Although thrombin (10(-7) M)
      and trypsin (10(-6) M) were tachyphylactic upon repeated administration, trypsin
      contracted the aorta following thrombin-induced contraction. LY287045 (10(-7) M)
      attenuated thrombin-induced vasorelaxation, but not vasoconstriction with -log
      K(B) of 8.4. LY287045 (10(-7) M) also attenuated vasorelaxation, but not
      vasoconstriction to trypsin, another serine-protease with a thrombin-like
      catalytic triad, with similar potency (-log K(B) = 8.6) to that for thrombin.
      Consistent with these vascular effects, LY287045 inhibited the protease activity
      of both thrombin and trypsin. To explore further the selective inhibitory effect
      of LY287045 on protease-induced relaxation, we examined the effect of LY287045 on
      the nitric oxide and prostacyclin pathways and found that LY287045 did not alter
      vascular responses mediated by nitric oxide or prostacyclin. Likewise, LY287045
      did not exert a direct inhibitory effect on the relaxant protease-activated
      receptor (PAR) since relaxation to the PAR-2-activating peptide was not blocked.
      The selective effect of LY287045 to inhibit only protease-induced endothelial
      dependent relaxation demonstrated that protease inhibition will not affect all
      protease responses equally. Furthermore, increases in trypsin and thrombin have
      been associated with inflammation and angiogenesis. To the extent that these
      findings suggest that LY287045 exhibit dual protease inhibition of endothelial
      responses, LY287045 may have specific utility in hypotensive inflammatory
      diseases and in cancer metastases where both trypsin and thrombin have been
      implicated as causative agents.

PMID- 11303046
TI  - Inverse agonist action of Leu-enkephalin at delta(2)-opioid receptors mediates
      spinal antianalgesia.
AB  - Dynorphin A(1-17) given intrathecally releases spinal cholecystokinin to produce
      an antianalgesic action against spinal morphine in the tail-flick test in CD-1
      mice. The present study showed that following the cholecystokinin step, a
      delta(2)-opioid inverse agonist action of Leu-enkephalin (LE), was involved.
      Pretreatment with intrathecal LE antiserum eliminated dynorphin and
      cholecystokinin-8s antianalgesia. A small dose of LE intrathecally produced
      antianalgesia that like that from dynorphin A(1-17) and cholecystokinin was
      eliminated by naltriben but not 7-benzylidenenaltrexone (delta(2)- and delta(1)
      opioid receptor antagonist, respectively). This LE step was followed by N-methyl
      D-aspartate (NMDA) receptor activation. MK801, an NMDA receptor antagonist,
      eliminated the antianalgesia from dynorphin A(1-17), cholecystokinin-8s, and LE.
      Furthermore, none of the three were effective against morphine analgesia in
      129S6/SvEv mice possibly because of their deficiency in NMDA receptor response.
      In 129S6/SvEv mice, [D-Ser(2)]-Leu-enkephalin-Thr analgesia was not attenuated by
      LE; thus, this delta(2)-analgesic agonist and LE inverse agonist action did not
      occur through competition at the same delta(2)-receptor in CD-1 mice. In CD-1
      mice, a linear sequence of dynorphin A(1-17) --> cholecystokinin --> LE --> NMDA
      receptors was indicated: cholecystokinin antiserum inhibited cholecystokinin but
      not LE; naltriben inhibited LE but not NMDA. The uniqueness of LE in linking
      dynorphin A(1-17), cholecystokinin, delta(2)-opioid, and NMDA receptor activation
      may unify the separate known mechanisms involved in the antiopioid actions of
      these components against morphine.

PMID- 11303047
TI  - Beta-endorphin-induced feeding: pharmacological characterization using selective
      opioid antagonists and antisense probes in rats.
AB  - Ventricular administration of the opioid beta END induces feeding in rats. Since
      its pharmacological characterization has not been fully identified, the present
      study examined whether equimolar doses of general and selective opioid
      antagonists as well as AS ODN opioid probes altered spontaneous daytime feeding
      over a 4-h time course elicited by beta END. beta END-induced feeding was
      significantly reduced by moderate (20--40-nmol, i.c.v.) doses of general
      (naltrexone) opioid antagonists, and lower (0.5--40-nmol) doses of selective mu
      (beta-funaltrexamine)-antagonists. Correspondingly, AS ODN probes directed
      against either exons 1, 3, or 4, but not exon 2, of the mu-opioid receptor clone
      reduced beta END-induced feeding; a missense ODN control probe was ineffective.
      The delta-antagonist Nti (20-40 nmol) reduced beta END-induced feeding to a
      lesser degree, and AS ODN probes targeting exon 1, but not 2 or 3, of the delta
      opioid receptor clone significantly reduced beta END-induced feeding. Although
      the selective kappa(1)-receptor antagonist NBNI (20-40 nmol) significantly
      reduced beta END-induced feeding, this response was not altered by AS ODN probes
      directed against either exons 1, 2, or 3 of either the KOR-1 clone or the
      kappa(3)-like opioid receptor clone. These converging antagonist and AS ODN data
      firmly implicate the mu-opioid receptor in the mediation of beta END-induced
      feeding. The relative lack of convergence between the lesser effectiveness of Nti
      and NBNI in reducing beta END-induced feeding, and the lack of effectiveness of
      their corresponding AS ODN probes suggest that delta- and kappa-receptors play a
      minimal role in the mediation of this response.

PMID- 11303048
TI  - In vivo pharmacological characterization of SoRI 9409, a nonpeptidic opioid mu
      agonist/delta-antagonist that produces limited antinociceptive tolerance and
      attenuates morphine physical dependence.
AB  - Repeated exposure to mu-opioid analgesics produces unwanted side effects,
      including tolerance and physical dependence. delta-Opioid antagonists attenuate
      development of morphine tolerance and physical dependence. We recently reported
      that SoRI 9409, a mixed mu-agonist/delta-antagonist, produces antinociception
      with limited development of tolerance after repeated i.c.v. injections. The
      current studies report on a more complete characterization of the compound in
      male ICR mice. SoRI 9409 produced limited antinociceptive effects in the 55
      degrees C tail-flick test and full agonist effects in the acetic acid writhing
      assay after i.c.v. or i.p. administration. Repeated i.p. administration of A(90)
      doses of SoRI 9409 did not produce tolerance. The agonist effects of the compound
      were preferentially blocked by the mu-selective antagonist beta-funaltrexamine.
      The kappa-antagonist nor-binaltorphimine produced partial antagonism, whereas the
      delta-antagonist naltrindole had no effect on SoRI 9409 antinociception.
      Intraperitoneal administration of SoRI 9409 preferentially antagonized the
      antinociceptive actions of the delta-2 agonist [D-Ala(2),Glu(4)]deltorphin over
      the delta-1 agonist cyclic[D-Pen(2),D-Pen(5)]-enkephalin and the mu-agonist [D
      Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin. SoRI 9409 did not antagonize the
      antinociceptive effects of the kappa-agonist U69,593 (doses up to 60 mg/kg). SoRI
      9409 (10 mg/kg i.p.) elicited much less vertical jumping than naloxone (10 mg/kg
      i.p.) in acute and chronic morphine dependence models. SoRI 9409 also suppressed
      withdrawal jumping when coadministered with naloxone. These studies indicate that
      SoRI 9409 acts primarily as a partial mu-agonist/delta-antagonist and supports
      the hypothesis that this type of compound may have a better therapeutic profile
      than currently available mu-agonists.

PMID- 11303049
TI  - RXP 407, a selective inhibitor of the N-domain of angiotensin I-converting
      enzyme, blocks in vivo the degradation of hemoregulatory peptide acetyl-Ser-Asp
      Lys-Pro with no effect on angiotensin I hydrolysis.
AB  - The phosphinic peptide RXP 407 has recently been identified as the first potent
      selective inhibitor of the N-active site (domain) of angiotensin-converting
      enzyme (ACE) in vitro. The aim of this study was to probe the in vivo efficacy of
      this new ACE inhibitor and to assess its effect on the metabolism of AcSDKP and
      angiotensin I. In mice infused with increasing doses of RXP 407 (0.1--30 mg/kg/30
      min), plasma concentrations of AcSDKP, a physiological substrate of the N-domain,
      increased significantly and dose dependently toward a plateau 4 to 6 times the
      basal levels. RXP 407 significantly and dose dependently inhibited ex vivo plasma
      ACE N-domain activity, whereas it had no inhibitory activity toward the ACE C
      domain. RXP 407 (10 mg/kg) did not inhibit the pressor response to an i.v.
      angiotensin I bolus injection in mice. In contrast, lisinopril infusion (5 and 10
      mg/kg/30 min) affected the metabolism of both AcSDKP and angiotensin I. Thus, RXP
      407 is the first ACE inhibitor that might be used to control selectively AcSDKP
      metabolism with no effect on blood pressure regulation.

PMID- 11303050
TI  - Blockade of delta opioid receptors in the ventrolateral periaqueductal gray
      region inhibits the fall in arterial pressure evoked by hemorrhage.
AB  - Severe hemorrhage lowers arterial pressure by suppressing sympathetic activity.
      The central mechanism that initially triggers the fall in arterial pressure
      evoked by hemorrhage is not well understood, although opioid neurons are thought
      to play a role. This study tested the hypothesis that hemorrhagic hypotension is
      mediated by delta opioid receptors in the ventrolateral periaqueductal gray
      (vlPAG), a region importantly involved in opioid analgesia. Depressor sites were
      first identified by microinjecting DL-homocysteic acid (20 nmol/0.1 microl) or
      beta-endorphin (0.5 nmol/0.1 microl) into the vlPAG of halothane-anesthetized
      rats. Consistent with earlier reports, DL-homocysteic acid injection into the
      caudal vlPAG lowered arterial pressure and heart rate; beta-endorphin evoked a
      comparable depressor response, but did not affect heart rate. Naloxone or
      selective opioid receptor antagonists were subsequently injected into the vlPAG 5
      min before hemorrhage (1.9 or 2.5 ml/100 g of body weight over 20 min) was
      initiated using the same stereotaxic coordinates. Naloxone injection into the
      caudal vlPAG completely prevented the fall in arterial pressure evoked by
      hemorrhage. The response was dose-dependent and evident with both fixed volume
      and fixed pressure hemorrhage. The delta opioid receptor antagonist naltrindole
      inhibited hemorrhagic hypotension significantly in both conscious and
      anesthetized rats but mu and kappa receptor antagonists were ineffective. beta
      Endorphin(1--27), an endogenous opioid receptor antagonist, was also
      significantly inhibitory. Naltrindole was ineffective when injected into the
      dorsolateral periaqueductal gray and did not influence cardiovascular function in
      nonhemorrhaged animals. These data support the hypothesis that hemorrhagic
      hypotension is mediated by delta opioid receptors in the vlPAG.

PMID- 11303051
TI  - Effect of FK960, a putative cognitive enhancer, on synaptic transmission in CA1
      neurons of rat hippocampus.
AB  - The action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a
      novel cognitive enhancer, on excitatory synaptic transmission in the hippocampus
      was investigated. Excitatory postsynaptic potentials (EPSPs) and currents (EPSCs)
      were recorded intracellularly from CA1 neurons in rat hippocampus using the
      "blind patch" variant of whole-cell recording. FK960 (100 nM) significantly
      increased the amplitude of the EPSP, which was unchanged when changeover was made
      to control artificial cerebrospinal fluid (aCSF). FK960 had no significant action
      on membrane potential, input resistance, or the early GABAergic inhibitory
      postsynaptic current. The decay phase of the excitatory postsynaptic current was
      not significantly altered by exposure to FK960, indicating that the properties of
      desensitization and/or deactivation were unchanged and suggesting that the action
      of FK960 was unlikely to be the result of changes in the properties of the
      postsynaptic (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)
      receptors. The quantal content of the EPSP (1/CV(2)) increased after exposure to
      FK960 but not to control aCSF. Methyllycaconitine or alpha-bungarotoxin blocked
      the modulatory action of FK960 on the EPSP, and the finding that these alpha 7
      nicotinic acetylcholine receptor (alpha 7nAChR) antagonists were effective raises
      the possibility that FK960 up-regulates the contribution of acetylcholine to
      synaptic efficacy in the hippocampus. It is concluded that FK960 increases the
      quantal release of glutamate from Schaffer collateral-commissural nerve terminals
      in area CA1 of the hippocampus either by changing the ambient level of
      acetylcholine or by positively modulating the activity of alpha 7nAChRs located
      on glutamatergic nerve terminals.

PMID- 11303052
TI  - Cannabinoid CB(1) receptor agonists produce cerebellar dysfunction in mice.
AB  - The purpose of these studies was to characterize the effects of agonists of the
      CB(1) cannabinoid receptor on cerebellar function in mice. We used two measures
      specific for cerebellar function: gait analysis and the bar cross test. CB(1)
      receptor agonists CP55940, Win 55212-2, Delta(9)-tetrahydrocannabinol,
      arachidonylethanolamide (AEA), and two AEA analogs with high affinity for the
      CB(1) receptor (arachidonyl-2-chloroethylamide and arachidonylcyclopropylamide)
      all produced increases in gait width, a measure of truncal ataxia. All of the
      CB(1) agonists tested significantly increased the number of slips on the bar
      cross test, which is consistent with motor incoordination. Pretreatment with the
      CB(1) receptor antagonist SR141716 attenuated both the change in gait width and
      number of slips induced by CP55940 and AEA. Neither cannabidiol nor Win 55212-3
      affected these measures, further evidence that this effect is mediated by the
      CB(1) receptor. Pretreatment with the dopamine receptor agonists apomorphine or
      bromocriptine did not attenuate the diminished performance on the bar cross or
      the gait abnormality induced by CP55940. These data indicate that the assays used
      in this study are specific for cerebellar-mediated behavioral deficits, and that
      these deficits are not mediated by the basal ganglia or cannabinoid-induced
      alterations in nigrostriatal dopaminergic transmission. Other well known effects
      of cannabinoids in mice, such as hyperreflexia exemplified by jumping or
      "popcorn" behavior and postural hypotonia are discussed in relationship to
      cerebellar dysfunction and a working model of the effects of CB(1) receptor
      activation on cerebellar circuitry is presented.

PMID- 11303053
TI  - Pharmacokinetics of celecoxib after oral administration in dogs and humans:
      effect of food and site of absorption.
AB  - Celecoxib pharmacokinetics was evaluated after single and multiple oral dosing;
      after dosing in a solution and as a solid; with and without food; and after
      administration into different sites of the GI tract using dog. After oral dosing
      in a solution, celecoxib was rapidly absorbed and reached maximum concentrations
      by 1 h; absorption was delayed another 1 to 2 h when administered as a solid. The
      absolute bioavailability of celecoxib was higher when given as a solution (64-
      88%) compared with capsule (22--40%). The absorption of celecoxib given in a
      capsule was delayed by food, although systemic exposure increased by 3- to 5
      fold. The systemic availability of celecoxib given intragastrically in solution
      was similar to that obtained following direct instillation into the duodenum,
      jejunum, or colon through a chronic intestinal access port. Collectively, these
      data suggest that celecoxib is a highly permeable drug that can be absorbed
      throughout the GI tract and that dissolution may be a rate-limiting factor for
      absorption from solid dosage forms. Unlike dogs, celecoxib given to humans with a
      high fat meal exhibits only a slight increase in AUC(0--infinity) (11%) that is
      not clinically significant with regard to safety or efficacy. In humans, a lower
      dose and a longer GI residence time may promote the opportunity for absorption of
      a poorly soluble drug such as celecoxib that can be absorbed throughout the GI
      tract. This would minimize the effect of food on absorption; as such, patients
      with arthritis can be given celecoxib with or without food.

PMID- 11303054
TI  - Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes.
AB  - Because mecamylamine, a nicotinic receptor antagonist, is used so often in
      nicotine research and because mecamylamine may have important therapeutic
      properties clinically, it is important to fully explore and understand its
      pharmacology. In the present study, the efficacy and potency of mecamylamine and
      its stereoisomers were evaluated as inhibitors of human alpha 3 beta 4, alpha 3
      beta 2, alpha 7, and alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs),
      as well as mouse adult type muscle nAChRs and rat N-methyl-D-aspartate (NMDA)
      receptors expressed in Xenopus oocytes. The selectivity of mecamylamine for
      neuronal nAChR was manifested primarily in terms of slow recovery rates from
      mecamylamine-induced inhibition. Neuronal receptors showed a prolonged inhibition
      after exposure to low micromolar concentrations of mecamylamine. Muscle-type
      receptors showed a transient inhibition by similar concentrations of
      mecamylamine, and NMDA receptors were only transiently inhibited by higher
      micromolar concentrations. Mecamylamine inhibition of neuronal nAChR was
      noncompetitive and voltage dependent. Although there was little difference
      between S-(+)-mecamylamine and R-(-)-mecamylamine in terms of 50% inhibition
      concentration values for a given receptor subtype, there appeared to be
      significant differences in the off-rates for the mecamylamine isomers from the
      receptors. Specifically, S-(+)-mecamylamine appeared to dissociate more slowly
      from alpha 4 beta 2 and alpha 3 beta 4 receptors than did R-(-)-mecamylamine. In
      addition, it was found that muscle-type receptors appeared to be somewhat more
      sensitive to R-(-)-mecamylamine than to S-(+)-mecamylamine. Together, these
      findings suggest that in chronic (i.e., therapeutic) application, S-(+)
      mecamylamine might be preferable to R-(-)-mecamylamine in terms of equilibrium
      inactivation of neuronal receptors with decreased side effects associated with
      muscle-type receptors.

PMID- 11303055
TI  - Up-regulation of cell surface sodium channels by cyclosporin A, FK506, and
      rapamycin in adrenal chromaffin cells.
AB  - Treatment of cultured bovine adrenal chromaffin cells with cyclosporin A (CsA)
      increased cell surface [(3)H]saxitoxin ([(3)H]STX) binding by 56% in a time
      (t(1/2) = 15.2 h)- and concentration (EC(50) = 2.9 microM)-dependent manner but
      did not change the K(d) value. In CsA-treated cells, veratridine-induced
      (22)Na(+) influx was augmented with no change in the EC(50) of veratridine; also,
      alpha- and beta-scorpion venom and Ptychodiscus brevis toxin-3 enhanced
      veratridine-induced (22)Na(+) influx in a more than additive manner, as in
      nontreated cells. CsA treatment for 1 to 24 h inhibited calcineurin activity,
      measured by the in vitro assay, with the IC(50) of 0.6 microM but did not alter
      cellular level of calcineurin. FK506 or rapamycin elevated [(3)H]STX binding by
      36 or 25%, whereas GPI-1046, an immunophilin ligand incapable to inhibit
      calcineurin, or okadaic acid, an inhibitor of protein phosphatases 1 and 2A, had
      no increasing effect. The rise of [(3)H]STX binding by CsA was attenuated by the
      coincident treatment with brefeldin A (BFA), an inhibitor of vesicular exit from
      the trans-Golgi network. The internalization rate of cell surface Na(+) channels,
      as determined in the presence of BFA, was decreased in CsA (but not rapamycin)
      treated cells (t(1/2) = 20.3 h), compared with nontreated cells (t(1/2) = 13.7
      h). CsA treatment, however, did not elevate cellular levels of Na(+) channel
      alpha-subunit and Na(+) channel alpha- and beta(1)-subunit mRNAs. In CsA-treated
      cells, veratridine-induced (45)Ca(2+) influx via voltage-dependent Ca(2+)
      channels and catecholamine secretion were enhanced, whereas high K(+)-induced
      (45)Ca(+) influx was not. Thus, the inhibition of calcineurin or rapamycin
      binding protein causes up-regulation of cell surface functional Na(+) channels
      via modulating externalization and internalization of Na(+) channels, thus
      enhancing Ca(2+) channel gating and catecholamine secretion.

PMID- 11303056
TI  - Pharmacological characterization of KUR-1246, a selective uterine relaxant.
AB  - The aim of the present study was to evaluate the efficacy and beta 2-adrenoceptor
      (AR) selectivity of KUR-1246, a new uterine relaxant. Inhibition of spontaneous
      or drug-induced uterine contractions by KUR-1246 was evaluated in pregnant rats
      and rabbits by an organ bath method or by a balloon method. The selectivity of
      KUR-1246 was assessed simultaneously in organs isolated from late-pregnant rats.
      The affinity of KUR-1246 for human beta 1-, beta 2-, and beta 3-ARs was
      determined using two radioligands. KUR-1246 suppressed both spontaneous and drug
      induced contractions in isolated uteri, the rank order of potency being
      isoproterenol > KUR-1246 > terbutaline > ritodrine. ICI-118551 (selective beta 2
      AR antagonist) competitively antagonized the KUR-1246-induced inhibition of
      spontaneous uterine contractions, but CGP-20712A (selective beta 1-AR antagonist)
      and SR-58894A (selective beta 3-AR antagonist) did not. All beta-AR agonists
      tested produced significant inhibition of spontaneous uterine contractions in
      vivo: ED(30) value for KUR-1246 was 0.13 microg/kg/min, a potency about 6 times
      and 400 times greater than that of terbutaline and ritodrine, respectively. In
      contrast, the positive chronotropic effect was minimal in KUR-1246-treated rats.
      KUR-1246 displaced radioligand binding to beta 1-, beta 2-, and beta 3-ARs, the
      pK(i) values being 5.75 +/- 0.03, 7.59 +/- 0.08, and 4.75 +/- 0.03 for beta 1-,
      beta 2-, and beta 3-ARs, respectively. For the selectivity of KUR-1246 for human
      beta 2-AR, we obtained values of 39.2 ([IC(50) for beta 1-AR]/[IC(50) for beta 2
      AR]) and 198.2 ([IC(50) for beta 3-AR]/[IC(50) for beta 2-AR]), indicating an
      apparently higher affinity for human beta 2-AR than for other beta-AR subtypes.
      The present study clearly demonstrated that KUR-1246 is a more selective beta 2
      AR agonist than the drugs presently used for relaxing uterine muscle.

PMID- 11303057
TI  - Pharmacological evidence for a 7-benzylidenenaltrexone-preferring opioid receptor
      mediating the inhibitory actions of peptidic delta- and mu-opioid agonists on
      neurogenic ion transport in porcine ileal mucosa.
AB  - The antidiarrheal and constipating effects of opiates are partly attributed to
      reductions in active anion secretion across the intestinal mucosa that are
      modulated by submucosal neurons. In this study, the opioid receptor mediating the
      actions of opioids on ion transport was characterized in mucosa-submucosa sheets
      from porcine ileum. Electrical transmural stimulation evoked transient increases
      in short-circuit current, an electrical measure of neurogenic ion transport, in
      this preparation. After serosal addition, the peptidic delta-opioid agonists [D
      Ala(2)]-deltorphin II (pIC(50) = 8.4 +/- 0.7), [D-Ala(2),D-Leu(5)]-enkephalin
      (DADLE), [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE), and [D-Ser(2),Leu(5),Thr(6)]
      enkephalin (DSLET), and the mu-opioid agonists [D-Ala(2),N-methyl-Phe(4),Gly(5)
      ol]-enkephalin (DAMGO) (pIC(50) = 8.0 +/- 0.1), endomorphin I, and PL-017
      inhibited short-circuit current elevations. Nonpeptidic mu- or delta-opioid
      agonists (morphine, loperamide, and SNC80) and kappa-opioid agonists (U-50,488H
      and U-69,593) were <360-fold less potent than deltorphin II. At 100 nM, the
      delta(1)-opioid antagonist 7-benzylidenenaltrexone reduced the potencies of DPDPE
      and DAMGO by 13.5- and 15.5-fold, respectively; at an identical concentration
      naltriben, a delta(2)-opioid antagonist, or the mu-opioid antagonist D-Phe-Cys
      Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) reduced DPDPE potency by 4.1- and 3.4
      fold, respectively, but had no significant effect on DAMGO potency. Using primary
      antisera directed toward cloned opioid receptors, delta-opioid receptor
      immunoreactivity was immunohistochemically localized in submucosal neurons and
      nerve fibers, but immunoreactivities to kappa- or mu-opioid receptors were not
      detected in the mucosa-submucosa. These results suggest that a novel 7
      benzylidenenaltrexone-sensitive opioid receptor is expressed in submucosal
      neurons of the porcine ileum, which mediates the inhibitory effects of peptidic
      mu- and delta-opioid agonists on neurogenic ion transport.

PMID- 11303058
TI  - Antidepressant drug-induced alterations in neuron-localized tumor necrosis factor
      alpha mRNA and alpha(2)-adrenergic receptor sensitivity.
AB  - The pleiotropic cytokine tumor necrosis factor-alpha (TNF) and alpha(2)
      adrenergic receptor activation regulate norepinephrine (NE) release from neurons
      in the central nervous system. The present study substantiates the role of TNF as
      a neuromodulator and demonstrates a reciprocally permissive relationship between
      the biological effects of TNF and alpha(2)-adrenergic receptor activation as a
      mechanism of action of antidepressant drugs. Immunohistochemical analysis and in
      situ hybridization reveal that administration of the antidepressant drug
      desipramine decreases the accumulation of constitutively expressed TNF mRNA in
      neurons of the rat brain. Superfusion and electrical field stimulation were
      applied to a series of rat hippocampal brain slices to study the regulation of
      [(3)H]NE release. Superfusion of hippocampal slices obtained from rats
      chronically administered the antidepressant drug zimelidine demonstrates that TNF
      mediated inhibition of [(3)H]NE release is transformed, such that [(3)H]NE
      release is potentiated in the presence of TNF, an effect that occurs in
      association with alpha(2)-adrenergic receptor activation. However, chronic
      zimelidine administration does not alter stimulation-evoked [(3)H]NE release,
      whereas chronic desipramine administration increases stimulation-evoked [(3)H]NE
      release and concomitantly decreases alpha(2)-adrenergic autoreceptor sensitivity.
      Collectively, these data support the hypothesis that chronic antidepressant drug
      administration alters alpha(2)-adrenergic receptor-dependent regulation of NE
      release. Additionally, these data demonstrate that administration of dissimilar
      antidepressant drugs similarly transform alpha(2)-adrenergic autoreceptors that
      are functionally associated with the neuromodulatory effects of TNF, suggesting a
      possible mechanism of action of antidepressant drugs.

PMID- 11303059
TI  - Comparison of pharmacological activities of buprenorphine and norbuprenorphine:
      norbuprenorphine is a potent opioid agonist.
AB  - Buprenorphine (BUP) is an oripavine analgesic that is beneficial in the
      maintenance treatment of opiate-dependent individuals. Although BUP has been
      studied extensively, relatively little is known about norbuprenorphine (norBUP),
      a major dealkylated metabolite of BUP. We now describe the binding of norBUP to
      opioid and nociceptin/orphanin FQ (ORL1) receptors, and its effects on
      [(35)S]guanosine-5'-O-(gamma-thio)triphosphate ([(35)S]GTP gamma S) binding
      mediated by opioid or ORL1 receptors and in the mouse acetic acid writhing test.
      Chinese hamster ovary cells stably transfected with each receptor were used for
      receptor binding and [(35)S]GTP gamma S binding. NorBUP exhibited high affinities
      for mu-, delta-, and kappa-opioid receptors with K(i) values in the nanomolar or
      subnanomolar range, comparable to those of BUP. NorBUP and BUP had low affinities
      for the ORL1 receptor with K(i) values in the micromolar range. In the [(35)S]GTP
      gamma S binding assay, norBUP displayed characteristics distinct from BUP. At the
      delta-receptor, norBUP was a potent full agonist, yet BUP had no agonist activity
      and antagonized actions of norBUP and DPDPE. At mu- and kappa-receptors, both
      norBUP and BUP were potent partial agonists, with norBUP having moderate efficacy
      and BUP having low efficacy. At the ORL1 receptor, norBUP was a full agonist with
      low potency, while BUP was a potent partial agonist. In the writhing test, BUP
      and norBUP both suppressed writhing in an efficacious and dose-dependent manner,
      giving A(50) values of 0.067 and 0.21 mg/kg, s.c., respectively. These results
      highlight the similarities and differences between BUP and norBUP, each of which
      may influence the unique pharmacological profile of BUP.

PMID- 11303061
TI  - Selective interactions of the human immunodeficiency virus-inactivating protein
      cyanovirin-N with high-mannose oligosaccharides on gp120 and other glycoproteins.
AB  - The virucidal protein cyanovirin-N (CV-N) mediates its highly potent anti-human
      immunodeficiency virus activity, at least in part, through interactions with the
      viral envelope glycoprotein gp120. Here we dissect in further detail the
      mechanism of CV-N's glycosylation-dependent binding to gp120. Isothermal
      titration calorimetry (ITC) binding studies of CV-N with endoglycosidase H
      treated gp120 showed that binding was completely abrogated by removal of high
      mannose oligosaccharides from the glycoprotein. Additional ITC and circular
      dichroism spectral studies with CV-N and other glycoproteins as well showed that
      CV-N discriminately bound only glycoproteins that contain high-mannose
      oligosaccharides. Binding experiments with RNase B indicated that the single high
      mannose oligosaccharide on that enzyme mediated all of its binding with CV-N
      (K(d) = 0.602 microM). A finer level of oligosaccharide selectivity of CV-N was
      revealed in affinity chromatography-liquid chromatography-mass spectrometry
      experiments, which showed that CV-N preferentially bound only oligomannose-8 (Man
      8) and oligomannose-9 isoforms of RNase B. Finally, we biophysically
      characterized the interaction of CV-N with a purified, single oligosaccharide,
      Man-8. The binding affinity of Man-8 for CV-N is unusually strong (K(d) = 0.488
      microM), several hundredfold greater than observed for oligosaccharides and their
      protein lectins (K(d) = 1 microM--1 mM), further establishing a critical role of
      high-mannose oligosaccharides in CV-N binding to glycoproteins.

PMID- 11303060
TI  - Electrophysiological effects of cocaethylene, cocaine, and ethanol on
      dopaminergic neurons of the ventral tegmental area.
AB  - Coabuse of ethanol and cocaine is one of the most commonly used drug combinations
      and results in the formation of cocaethylene by the liver. Dopaminergic neurons
      of the ventral tegmental area (VTA) play a key role in the rewarding properties
      of drugs of abuse, including ethanol and cocaine. We have previously examined the
      electrophysiological effects of ethanol and cocaine, and their combined effects
      on these neurons. The present study investigates the electrophysiological effects
      of cocaethylene on dopaminergic VTA neurons with extracellular single-unit
      recording in brain slices from Fischer 344 rats. Cocaethylene (1--10 microM)
      decreased the firing rate of dopaminergic VTA neurons, similar to the effect of
      cocaine over this concentration range. This inhibition was blocked by the D(2)
      dopamine receptor antagonist, sulpiride (2 microM). At a lower concentration,
      cocaethylene (500 nM) potentiated ethanol-induced excitation of these neurons,
      similar to the effect of cocaine (500 nM) previously reported. This potentiation
      of ethanol excitation by cocaethylene was reversed by the 5-HT(2) antagonist
      ketanserin (5 microM). These data suggest that cocaethylene acts through a
      serotonergic mechanism at low concentrations to potentiate ethanol excitation of
      reward neurons and through a dopaminergic mechanism at high concentrations. The
      potency of cocaethylene in both of these actions is similar to that of cocaine.
      These effects of cocaethylene are likely to contribute to the synergistic effect
      on the dopaminergic reward pathway when ethanol and cocaine are used together;
      this may help to explain the high incidence of coabuse of ethanol and cocaine.

PMID- 11303062
TI  - Long-term effects of olanzapine, risperidone, and quetiapine on dopamine receptor
      types in regions of rat brain: implications for antipsychotic drug treatment.
AB  - Changes in members of the dopamine (DA) D(1)-like (D(1), D(5)) and D(2)-like
      (D(2), D(3), D(4)) receptor families in rat forebrain regions were compared by
      quantitative in vitro receptor autoradiography after prolonged treatment (28
      days) with the atypical antipsychotics olanzapine, risperidone, and quetiapine.
      Olanzapine and risperidone, but not quetiapine, significantly increased D(2)
      binding in medial prefrontal cortex (MPC; 67% and 34%), caudate-putamen (CPu;
      average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippocampus (HIP; 53%,
      30%). Olanzapine and risperidone, but not quetiapine, produced even greater up
      regulation of D(4) receptors in CPu (61%, 37%), NAc (65%, 32%), and HIP (61%,
      37%). D(1)-like and D(3) receptors in all regions were unaltered by any
      treatment, suggesting their minimal role in mediating actions of these
      antipsychotics. The findings support the hypothesis that antipsychotic effects of
      olanzapine and risperidone are partly mediated by D(2) receptors in MPC, NAc, or
      HIP, and perhaps D(4) receptors in CPu, NAc, or HIP, but not in cerebral cortex.
      Selective up-regulation of D(2) receptors by olanzapine and risperidone in CPu
      may reflect their ability to induce some extrapyramidal effects. Inability of
      quetiapine to alter DA receptors suggests that nondopaminergic mechanisms
      contribute to its antipsychotic effects.

PMID- 11303063
TI  - Molecular and pharmacological characterization of muscarinic receptor subtypes in
      a rat parotid gland cell line: comparison with native parotid gland.
AB  - The molecular and pharmacological characteristics of muscarinic receptor subtypes
      in the rat parotid acinar cell line, PAR-C5, were determined and compared with
      native rat parotid glands to evaluate the PAR-C5 cell line as a model to study
      receptor-mediated secretion. Reverse transcription-polymerase chain reaction (RT
      PCR) identified mRNAs for M(3), M(4), and M(5) receptor subtypes in both PAR-C5
      cells and parotid glands. Specific [N-methyl-(3)H]scopolamine binding in PAR-C5
      and parotid membranes was to a single class of sites with mean K(D) values of
      0.38 and 0.64 nM, respectively. Binding affinities (K(I) values) of muscarinic
      receptor subtype-selective drugs were obtained in side-by-side experiments
      comparing PAR-C5 cells with parotid glands. Nonlinear regression analysis
      indicated that competition binding curves for drugs in PAR-C5 cells and parotid
      glands fit best to a one-site binding model. K(I) values (nM) in PAR-C5 cells and
      parotid glands, respectively, for atropine (1.0, 2.1), darifenacin (1.2, 2.0), 4
      diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (2.9, 2.4), tripitramine
      (220, 180), pirenzepine (320, 720), and methoctramine (1400, 1700) were
      consistent with their known affinities at the M(3) receptor subtype. Affinities
      (K(B) values) of muscarinic receptor subtype-selective drugs for blocking
      methacholine-stimulated Ca(2+) mobilization were determined to show which subtype
      mediates Ca(2+)-dependent secretion in Fura-2-loaded PAR-C5 cells. K(B) values
      (nM) for atropine (0.44), 4-DAMP (0.38), pirenzepine (140), and methoctramine
      (320) for blocking Ca(2+) responses correlated well with their known affinities
      at the M(3) receptor (r(2) = 0.99). These results show that at the level of mRNA,
      receptor protein and function, PAR-C5 cells and parotid glands are similar,
      establishing PAR-C5 cells as an important model for muscarinic receptor-mediated
      secretion.

PMID- 11303064
TI  - Differential effect of gabapentin on neuronal and muscle calcium currents.
AB  - Calcium channels modulate cell function by controlling Ca(2+) influx. A main
      component of these proteins is the alpha 2/delta subunit. Nevertheless, how this
      subunit regulates channel activity in situ is unclear. Gabapentin (GBP), an
      analgesic and anti-epileptic agent with an unknown mechanism of action,
      specifically binds to the alpha 2/delta subunit. Using the patch clamp technique,
      we tested the effects of GBP on Ca(2+) currents from dorsal root ganglion (DRG)
      cells, the mediators of pain perception, to determine how GBP binding modifies
      channel activity. In DRGs, GBP significantly reduced whole cell Ca(2+) current
      amplitude at positive membrane potentials when a pulse preceded the test pulses
      or when cells were stimulated with a train of pulses. In control cells, neither
      prepulse depolarization nor pulse trains reduced Ca(2+) currents at positive
      potentials. GBP did not reduce the low-voltage activated Ca(2+) current under any
      experimental condition. Similar to DRG cells, GBP attenuated Ca(2+) current in
      skeletal myotubes at positive membrane potentials in the presence of a
      depolarizing prepulse. However, GBP did not significantly alter Ca(2+) currents
      in cardiac myocytes. Reverse transcription-polymerase chain reaction was used to
      confirm expression of the alpha 2/delta subunit in these cells. Each cell type
      expressed multiple isoforms of alpha 2/delta. Muscle cells showed a more variable
      expression of alpha 2/delta subunits than did DRG cells. Our results suggest a
      possible participation of the alpha 2/delta subunit in the action of GBP. Our
      data also indicate that GBP inhibits Ca(2+) channels in a use- and voltage
      dependent manner at a therapeutically relevant concentration.

PMID- 11303065
TI  - Regional vascular selectivity of angiotensin II.
AB  - To examine the actions of angiotensin II on regional vascular resistances, we
      monitored regional blood flows and cardiac output with transit-time flow probes
      and thermodilution, respectively, in anesthetized rats. To remove the influence
      of endogenous angiotensin II, rats were pretreated with captopril (30 mg/kg
      intravenously). Intravenous infusions of angiotensin II were used to produce
      circulating angiotensin II, and these infusions caused marked dose-related (3,
      30, and 300 pmol/min) and sustained (2 h) increases in renal vascular resistance,
      with lesser effects on mesenteric vascular resistance, little effect on carotid
      vascular resistance, and no effect on hindquarter or calculated "other tissue"
      vascular resistances. In contrast, vasopressin caused similar increases in renal,
      mesenteric, carotid, hindquarter, and other tissue vascular resistances.
      Infusions of angiotensin II (3, 10, and 30 pmol/min) into the local arterial
      blood were used to increase selectively local angiotensin II levels. Intrarenal
      artery infusions of angiotensin II increased renal, but not mesenteric, vascular
      resistance; and intramesenteric artery infusions of angiotensin II increased
      mesenteric, but not renal, vascular resistance. Infusions of angiotensin II into
      the hindquarter and carotid vascular beds caused little change in hindquarter and
      carotid vascular resistances, respectively, but sufficient angiotensin II escaped
      the hindquarter and carotid vascular beds to cause increases in renal and
      mesenteric vascular resistances. In conclusion, angiotensin II constricts
      primarily the renal vascular bed and to a lesser extent the gut circulation, and
      those tissues that are most responsive to angiotensin II also metabolize
      angiotensin II better than tissues that are less responsive to angiotensin II.

PMID- 11303066
TI  - Amphetamine normalizes the electrical activity of dopamine neurons in the ventral
      tegmental area following prenatal ethanol exposure.
AB  - Prenatal ethanol exposure has been shown to produce a persistent reduction in the
      spontaneous activity of ventral tegmental area (VTA) dopamine (DA) neurons and in
      DA neurotransmission. Amphetamine-like stimulants are effective in treating
      attention deficit/hyperactivity disorder (ADHD), which is a major symptom in
      fetal alcohol syndrome. Because there is a link between reduced DA
      neurotransmission and ADHD, we investigated the possibility that amphetamine
      could restore the spontaneous activity of VTA DA neurons. Pregnant rats were
      administered 0 or 6 g/kg/day ethanol via intragastric intubation during gestation
      days 8 to 20. The spontaneous activity of VTA neurons was studied in 6- to 8-week
      old male offspring using extracellular single-unit recording in unanesthetized
      (paralyzed, locally anesthetized) or chloral hydrate-anesthetized rats. Prenatal
      ethanol exposure reduced the number of spontaneously active DA neurons without
      changing the firing rate or firing pattern in both groups of animals. Acute
      amphetamine administration (2 mg/kg, i.v.) increased the number of spontaneously
      active DA neurons after prenatal ethanol exposure. Because amphetamine inhibited
      DA neuron firing rate in ethanol-exposed animals, it is possible that amphetamine
      restored the number of spontaneously active neurons by alleviating the
      depolarization block. These results show that the reduction in the number of
      spontaneously active DA neurons resulting from prenatal ethanol exposure is not
      confounded by using general anesthesia. Furthermore, acute amphetamine treatment
      can normalize the activity of DA neurons after prenatal ethanol exposure. This
      mechanism may contribute to the therapeutic effects of amphetamine-like
      stimulants in attention problems observed in children with fetal alcohol
      syndrome.

PMID- 11303067
TI  - High-affinity blockade of human ether-a-go-go-related gene human cardiac
      potassium channels by the novel antiarrhythmic drug BRL-32872.
AB  - Human ether-a-go-go-related gene (HERG) potassium channels are one primary target
      for the pharmacological treatment of cardiac arrhythmias by class III
      antiarrhythmic drugs. These drugs are characterized by high antiarrhythmic
      efficacy, but they can also initiate life-threatening "torsade de pointes"
      tachyarrhythmias. Recently, it has been suggested that combining potassium and
      calcium channel blocking mechanisms reduces the proarrhythmic potential of
      selective class III antiarrhythmic agents. BRL-32872 is a novel antiarrhythmic
      drug that inhibits potassium and calcium currents in isolated cardiomyocytes. In
      our study, we investigated the effects of BRL-32872 on cloned HERG channels
      heterologously expressed in Xenopus oocytes. Using the two-microelectrode voltage
      clamp technique, we found that BRL-32872 caused a high-affinity, state-dependent
      block of open HERG channels (IC(50) = 241 nM) in a frequency-dependent manner
      with slow unbinding kinetics. Inactivated channels mainly had to open to be
      blocked by BRL-32872. The HERG S620T mutant channel, which has a strongly reduced
      degree of inactivation, was 51-fold less sensitive to BRL-32872 block, indicating
      that BRL-32872 binding was enhanced by the inactivation process. In an additional
      approach, we studied HERG channels expressed in a human cell line (HEK 293) using
      the whole-cell patch-clamp technique. BRL-32872 inhibited HERG currents in HEK
      293 cells in a dose-dependent manner, with an IC(50) value of 19.8 nM. We
      conclude that BRL-32872 is a potent blocker of HERG potassium channels, which
      accounts for the class III antiarrhythmic action of BRL-32872.

PMID- 11303068
TI  - Inositol 1,4,5-triphosphate receptor-sensitive Ca(2+) release, store-operated
      Ca(2+) entry, and cAMP responsive element binding protein phosphorylation in
      developing cortical cells following exposure to polychlorinated biphenyls.
AB  - The present study assessed intracellular Ca(2+) signaling pathways sensitive to
      polychlorinated biphenyls (PCBs), xenobiotics that perturb neural development and
      plasticity. Mobilization of intracellular Ca(2+) stores after acute exposure to a
      PCB mixture, Aroclor 1254 (A1254), as well as selected PCB congeners, was studied
      in P0 rat cortical neuronal culture using fluorescence microscopy. Ca(2+)
      responses to A1254 progressed from a transient intracellular Ca(2+) increase
      (lasting 3--5 min) at 1 to 2 microM (0.3-0.6 ppm) to a Ca(2+) transient with
      store-operated Ca(2+) influx and later disturbances of basal Ca(2+)
      concentration; this latter pattern occurred more often with 10 to 20 microM (3--6
      ppm) A1254. Thapsigargin, xestospongin C, and carbachol/Ca(2+)-free buffer
      blocked significantly the PCB-induced Ca(2+) transient, whereas both ryanodine
      (to deplete ryanodine-sensitive stores) and the L-type Ca(2+) channel blocker
      nifedipine were without effect on the A1254 initial Ca(2+) transient. Both
      thapsigargin and xestospongin also blocked latent elevations (at 0.5 h) in
      Ca(2+), disturbances that depend upon extracellular Ca(2+) entry via ion
      channels. Two possible consequences were explored. Phosphorylation of cAMP
      responsive element binding protein, a Ca(2+)-activated nuclear transcription
      factor (CREB), occurred in an A1254 concentration-dependent manner and persisted
      at least 1 h. Cell viability following a 24-h exposure to A1254 (2-20 microM) was
      decreased at 20 microM, but only in cells cultured >6 days. This cell death did
      not occur via an apoptotic mechanism. These results indicate that Ca(2+)
      disturbances following PCB exposure are associated with 1) discrete alterations
      in IP(3) receptor-mediated signals and 2) activation of downstream events that
      impact developing cortical cells.

PMID- 11303069
TI  - Prevention of fetal demise and growth restriction in a mouse model of fetal
      alcohol syndrome.
AB  - Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with
      novel glial proteins regulated by vasoactive intestinal peptide, are shown now to
      provide protective intervention in a model of fetal alcohol syndrome. Fetal
      demise and growth restrictions were produced after intraperitoneal injection of
      ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities
      elicited by alcohol treatment during development are believed to be associated,
      in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit
      antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar
      combination of the peptides prevented the alcohol-induced fetal death and growth
      abnormalities. Pretreatment with NAP alone resulted in a significant decrease in
      alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on
      fetal survival after alcohol exposure, indicating a pharmacological distinction
      between the peptides. Biochemical assessment of the fetuses indicated that the
      combination peptide treatment prevented the alcohol-induced decreases in reduced
      glutathione. Peptide efficacy was evident with either 30-min pretreatment or with
      1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ
      indicated that 39% of the total radioactivity comigrated with intact peptide in
      the fetus 60 min after administration. These studies demonstrate that fetal death
      and growth restriction associated with prenatal alcohol exposure were prevented
      by combinatorial peptide treatment and suggest that this therapeutic strategy be
      explored in other models/diseases associated with oxidative stress.

PMID- 11303070
TI  - Structure-hepatic disposition relationships for cationic drugs in isolated
      perfused rat livers: transmembrane exchange and cytoplasmic binding process.
AB  - This work studied the structure-hepatic disposition relationships for cationic
      drugs of varying lipophilicity using a single-pass, in situ rat liver
      preparation. The lipophilicity among the cationic drugs studied in this work is
      in the following order: diltiazem > propranolol > labetalol > prazosin >
      antipyrine > atenolol. Parameters characterizing the hepatic distribution and
      elimination kinetics of the drugs were estimated using the multiple indicator
      dilution method. The kinetic model used to describe drug transport (the "two
      phase stochastic model") integrated cytoplasmic binding kinetics and belongs to
      the class of barrier-limited and space-distributed liver models. Hepatic
      extraction ratio (E) (0.30--0.92) increased with lipophilicity. The intracellular
      binding rate constant (k(on)) and the equilibrium amount ratios characterizing
      the slowly and rapidly equilibrating binding sites (K(S) and K(R)) increase with
      the lipophilicity of drug (k(on): 0.05--0.35 s(-1); K(S): 0.61--16.67; K(R): 0.36
      -0.95), whereas the intracellular unbinding rate constant (k(off)) decreases with
      the lipophilicity of drug (0.081--0.021 s(-1)). The partition ratio of influx
      (k(in)) and efflux rate constant (k(out)), k(in)/k(out), increases with
      increasing pK(a) value of the drug [from 1.72 for antipyrine (pK(a) = 1.45) to
      9.76 for propranolol (pK(a) = 9.45)], the differences in k(in/kout) for the
      different drugs mainly arising from ion trapping in the mitochondria and
      lysosomes. The value of intrinsic elimination clearance (CL(int)), permeation
      clearance (CL(pT)), and permeability-surface area product (PS) all increase with
      the lipophilicity of drug [CL(int) (ml x min(-1) x g(-1) of liver): 10.08--67.41;
      CL(pT) (ml x min(-1) x g(-1) of liver): 10.80--5.35; PS (ml x min(-1) x g(-1) of
      liver): 14.59--90.54]. It is concluded that cationic drug kinetics in the liver
      can be modeled using models that integrate the presence of cytoplasmic binding, a
      hepatocyte barrier, and a vascular transit density function.

PMID- 11303071
TI  - Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4
      yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel
      mucarinic antagonist with M(2)-sparing antagonistic activity.
AB  - We evaluated the pharmacological profiles of (2R)-N-[1-(6- aminopyridin-2
      ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2
      phenylacetamide(compound A), which is a novel muscarinic receptor antagonist with
      M(2)-sparing antagonistic activity. Compound A inhibited [(3)H]NMS binding to
      cloned human muscarinic m1, m2, m3, m4, and m5 receptors expressed in Chinese
      hamster ovary cells with K(i) values (nM) of 1.5, 540, 2.8, 15, and 7.7,
      respectively. In isolated rat tissues, compound A inhibited carbachol-induced
      responses with 540-fold selectivity for trachea (K(B) = 1.2 nM) over atria (K(B)
      = 650 nM). In in vivo rat assays, compound A inhibited acetylcholine-induced
      bronchoconstriction and bradycardia with intravenous ED(50) values of 0.022 mg/kg
      and >/=10 mg/kg, respectively. Furthermore, in dogs, compound A (0.1-1 mg/kg
      p.o.) dose dependently shifted the methacholine concentration-respiratory
      resistance curves. In mice, compound A (10 mg/kg i.v.) did not inhibit
      oxotremorine-induced tremor. The brain/plasma ratio (K(p)) of compound A (3 mg/kg
      i.v.) was 0.13 in rats; this K(p) was less than that of scopolamine (1.7) and
      darifenacin (0.24). The inhibition of compound A (3 mg/kg i.v.) on ex vivo
      binding in rat cerebral cortex was almost similar to that of NMS. These findings
      demonstrate that compound A has high selectivity for M(3) receptors over M(2)
      receptors, displays a potent, oral M(3) antagonistic activity without inhibition
      of central muscarinic receptors because of low brain penetration. It is well
      known that central muscarinic antagonists may have diverse CNS effects, and M(2)
      receptors regulate cardiac pacing and act as autoreceptors in the lung and
      bladder. Thus, compound A may have fewer cardiac or CNS side effects than
      nonselective compounds.

PMID- 11303072
TI  - Force spectroscopy between acetylcholine and single acetylcholinesterase
      molecules and the effects of inhibitors and reactivators studied by atomic force
      microscopy.
AB  - Force spectroscopy between a single acetylcholinesterase (AChE) molecule and its
      natural substrates was performed, and the effects of inhibitors and reactivators
      on the force spectrum were studied with atomic force microscopy (AFM). The force
      spectrum between normal AChE and its substrates had its special shape.
      Inhibitors, which inhibit AChE by occupying the active center of the enzyme,
      could change the force spectrum shape noticeably. Reactivators, which reactivate
      the inhibited AChE by pulling the inhibitor off the active center of the enzyme,
      could make the normal shape of force spectrum reappear. This meant the shape
      features of the force spectrum could be used as a good index to observe the time
      course of the interactions between a single AChE molecule and its special
      inhibitors and reactivators in real time. The results of the real-time
      observation demonstrated that the inhibition times of soman and sarin on AChE
      were longer than 2 h and that of eserine, a reversible inhibitor of AChE, was 34
      +/- 3 min. The reactivation time of HI-6 on soman-inhibited AChE was 6 +/- 2 min.
      These results indicated that AFM was a useful tool in pharmacology and
      toxicology, and could reveal time information of the interactions between AChE
      and its ligands.

PMID- 11303073
TI  - Cyclosporine and FK506 differentially regulate the sarcolemmal Na(+)-K(+) pump.
AB  - Cyclosporine A (CsA) and FK506, important immunosuppressants, have been shown to
      inhibit the enzymatic equivalent of the Na(+)-K(+) pump (Na(+), K(+)-ATPase) in
      renal tissue. A similar effect in the heart may contribute to the adverse effects
      of these agents that include calcification, contractile dysfunction, and altered
      calcium handling. However, inhibition of the pump has not been demonstrated in
      cardiac myocytes. We isolated single ventricular myocytes from control rabbits
      and from rabbits administered CsA or FK506 for 1 week. Na(+)-K(+) pump current
      (I(p)) was measured using the whole-cell patch-clamp technique. When patch
      pipettes contained Na(+) in a concentration ([Na](pip)) near physiological
      intracellular levels mean I(p) of cardiac myocytes from rabbits with serum CsA
      levels within the therapeutic range was significantly lower than mean I(p) of
      cardiac myocytes from controls. Treatment had no effect on I(p) measured using a
      [Na](pip) expected to nearly saturate intracellular binding sites. The CsA
      induced inhibition of I(p) was dependent on the K(+) concentration in pipette
      solutions. Mean I(p) in myocytes from rabbits with serum levels of FK506 within
      the therapeutic range was similar to mean I(p) in myocytes from controls, whereas
      FK506 in a dose inducing serum levels severalfold above the therapeutic range
      caused significant pump inhibition. Using ion-sensitive microelectrodes we showed
      the intracellular Na(+) activity in papillary muscles isolated from rabbits
      treated with CsA was significantly higher than in papillary muscles from control
      rabbits, indicating that CsA causes pump inhibition in intact myocytes with a
      physiological intracellular milieu.

PMID- 11303074
TI  - Characterization of the caspase inhibitor IDN-1965 in a model of apoptosis
      associated liver injury.
AB  - Previous studies have shown that caspase inhibitors are effective at protecting
      against anti-Fas antibody (alpha-Fas)-mediated liver injury/lethality. The
      purpose of these experiments was to characterize more fully the efficacy of a
      broad-spectrum, irreversible caspase inhibitor, IDN-1965 (N-[(1,3-dimethylindole
      2-carbonyl)valinyl]-3-amino-4-oxo-5-fluoropentanoic acid), in this model and the
      role of caspase inhibition in long-term protection. The ED(50) for IDN-1965 by
      i.p. administration, based on alanine aminotransferase activities, was 0.14
      mg/kg. The caspase inhibitor was also efficacious when administered intravenously
      and orally (ED(50) values of 0.04 and 1.2 mg/kg, respectively). Histologically,
      marked reduction in Fas-induced apoptosis with IDN-1965 (1 mg/kg, i.p.) was
      apparent at 6 h. Also, caspase 3-like activities were decreased in a dose
      dependent manner, but the inhibition of caspase activity was transient.
      Immunohistochemical studies demonstrated that IDN-1965 greatly reduced the
      activation of caspase 3. In survival studies, a single i.p. treatment of 1 mg/kg
      IDN-1965 or continuous i.p. infusion via osmotic pumps completely blocked
      lethality measured up to 7 days after alpha-Fas administration. IDN-1965 was also
      effective in inhibiting liver injury when administered as long as 3 h after or 1
      h before alpha-Fas administration. Lastly, Western blot analysis demonstrated
      that processing of caspases 3, 6, and 8, as well as Bid (a protein responsible
      for the release of mitochondrial cytochrome C and amplification of the apoptotic
      cascade) was inhibited by IDN-1965. In conclusion, the broad-spectrum caspase
      inhibitor IDN-1965 is markedly effective at inhibiting Fas-mediated apoptosis by
      multiple routes of administration. The therapeutic potential of caspase
      inhibitors appears promising for the treatment of apoptosis-mediated liver injury
      based on potency and postinsult efficacy.

PMID- 11303075
TI  - Effects of cannabinoids on sympathetic and parasympathetic neuroeffector
      transmission in the rabbit heart.
AB  - Cannabinoids elicit marked cardiovascular responses. It is not clear how
      peripheral effects on the autonomic nervous system contribute to these responses.
      The aim of the present study was to characterize the peripheral actions of
      cannabinoids on the autonomic innervation of the heart. Experiments were carried
      out on pithed rabbits. In the first series of experiments, postganglionic
      sympathetic cardioaccelerator fibers were stimulated electrically. The synthetic
      cannabinoid receptor agonists WIN55212-2 (0.005, 0.05, 0.5, and 1.5 mg kg(-1)
      i.v.) and CP55940 (0.003, 0.03, 0.3, and 1 mg kg(-1) i.v.) dose dependently
      inhibited the electrically evoked cardioacceleration. The inhibition by WIN55212
      2 (0.5 mg kg(-1) i.v.) was prevented by the CB(1) cannabinoid receptor antagonist
      SR141716A (0.5 mg kg(-1) i.v.). WIN55212-2 (0.5 mg kg(-1) i.v.) did not change
      the increase in heart rate evoked by injection of isoprenaline. In the second
      series of experiments, preganglionic vagal fibers were stimulated electrically.
      WIN55212-2 (0.005, 0.05, and 0.5 mg kg(-1) i.v.) and CP55940 (0.003, 0.03, and
      0.3 mg kg(-1) i.v.) dose dependently inhibited the stimulation-evoked decrease in
      heart rate. The inhibition produced by WIN55212-2 (0.005, 0.05, and 0.5 mg kg(-1)
      i.v.) was antagonized by SR141716A (0.5 mg kg(-1) i.v.). The results indicate
      that cannabinoids, by activating CB(1) cannabinoid receptors, inhibit sympathetic
      and vagal neuroeffector transmission in the heart. The mechanism of the
      sympathoinhibition is probably presynaptic inhibition of noradrenaline release
      from postganglionic sympathetic neurons. The mechanism of the inhibition of vagal
      activity was not clarified: cannabinoids may have an inhibitory action on both
      pre- and postganglionic vagal neurons.

PMID- 11303076
TI  - New challenges facing ill health in Gulf war veterans.

PMID- 11303077
TI  - Health and exposures of United Kingdom Gulf war veterans. Part I: The pattern and
      extent of ill health.
AB  - OBJECTIVES: To assess the health of United Kingdom Gulf war veterans, to compare
      their health to that of similar personnel not deployed, to describe patterns of
      ill health in both groups, and to estimate their extent. METHODS: Main Gulf
      (n=4795) and validation Gulf (n=4793) cohorts were randomly selected within
      strata from the population deployed to the Gulf and a non-Gulf cohort (n=4790)
      from those who were not sent. Seven years after the war subjects completed a
      questionnaire about their health in the past month, including 95 symptom
      questions and two manikins on which to shade areas of pain or numbness and
      tingling. Responses were subjected to a principal component analysis with
      rotation and to a cluster analysis within each cohort. Mean symptom score was
      used as a measure of severity. Areas shaded on the manikins were coded to
      indicate widespread pain and possible toxic neuropathy. RESULTS: A response of
      85.5% was achieved. Those who had been to the Gulf were more troubled by every
      symptom with a mean severity score (3.0) substantially greater than in the non
      Gulf cohort (1.7). Seven factors were extracted accounting for 48% of the
      variance. The scores on five factors (labelled psychological, peripheral,
      respiratory, gastrointestinal, and concentration) were significantly worse in
      those who had been to the Gulf. Symptoms suggestive of peripheral neuropathy were
      found more often (12.5%) in the Gulf than the non-Gulf (6.8%) cohorts. Widespread
      pain was also found more often (12.2% Gulf; 6.5% non-Gulf). Those who had been to
      the Gulf were found disproportionately (23.8%) in three clusters with high mean
      severity scores; only 9.8% of non-Gulf respondents were in these clusters. There
      was no evidence of an important excess in the use of alcohol, tobacco, or
      referral to hospital specialists by those who had been to the Gulf. For the same
      level of reported ill health those who had been to the Gulf were less likely to
      be referred to specialists than non-Gulf veterans. CONCLUSION: 7 Years after the
      war, the Gulf war veterans were more troubled about their health than those who
      had not been sent, with a substantial subgroup reporting a pattern of symptoms
      suggestive of a significant decline in health.

PMID- 11303078
TI  - Health and exposures of United Kingdom Gulf war veterans. Part II: The relation
      of health to exposure.
AB  - OBJECTIVES: To investigate whether, in personnel who served with the United
      Kingdom forces in the Gulf war, self reported exposures were related to symptoms
      in a way that was consistent, specific, and credible. METHODS: Responses to
      symptom and exposure questionnaires, completed 7 or more years after the war,
      were collected from 7971 subjects deployed in the Gulf, from two exposed cohorts,
      in a study with an overall response rate of 85.5%. Exposures were considered in
      three groups, those outside the control of the subjects, the use of prophylaxis,
      and indicators of susceptibility. Health indices derived from symptom
      questionnaires were related to reports of 14 exposures in these three groups in a
      series of multiple regression analyses to allow for confounding. The relation of
      exposure to complaints of widespread pain and to symptoms suggesting peripheral
      neuropathy were examined by logistic regression. RESULTS: Consistent but weak
      correlations between exposures and with health effects were found in independent
      analyses of the two (main and validation) cohorts. Three exposures outside the
      control of the subject, the number of inoculations, the number of days handling
      pesticides, and the days exposed to smoke from oil fires, were consistently and
      independently related to severity. The number of inoculations was also associated
      with higher scores on a factor weighted on symptoms associated with skin and
      musculoskeletal complaints. The number of days handling pesticides related
      particularly to scores on a neurological factor and to symptoms consistent with
      toxic neuropathy. CONCLUSION: The relations between exposures and ill health were
      generally weak. Consistent, specific, and credible relations, warranting further
      investigation, were found between health indices and two exposures, the reported
      number of inoculations and days handling pesticides.

PMID- 11303079
TI  - Leukaemia mortality in relation to magnetic field exposure: findings from a study
      of United Kingdom electricity generation and transmission workers, 1973-97.
AB  - OBJECTIVE: To investigate whether risks of leukaemia are related to occupational
      exposure to magnetic fields. METHODS: The mortality experienced by a cohort of 83
      997 employees of the former Central Electricity Generating Board of England and
      Wales was investigated for the period 1973-97. All employees were employed for at
      least 6 months with some employment in the period 1973-82. Computerised work
      histories were available for 79 972 study subjects for the period 1971-93.
      Detailed calculations were performed by others to enable a novel assessment to be
      made of exposures to magnetic fields. Two analytical approaches were used,
      indirect standardisation (n=83 997) and Poisson regression (n=79 972). RESULTS:
      Based on serial mortalities for England and Wales, the standardised mortality
      ratio of 84 for all leukaemias (observed 111, expected 132.3) was similar to that
      of 83 for all causes (observed 14 845, expected 17 918). No significant positive
      trends were found for the risks of various types of leukaemia (chronic lymphatic
      leukaemia, acute myeloid leukaemia, chronic myeloid leukaemia, all leukaemia)
      either with lifetime cumulative exposure to magnetic fields or with such
      exposures received in the most recent 5 years. CONCLUSIONS: There are no
      discernible excess risks of leukaemia as a consequence of occupational exposure
      to magnetic fields in United Kingdom electricity generation and transmission
      workers.

PMID- 11303080
TI  - Small area estimation of incidence of cancer around a known source of exposure
      with fine resolution data.
AB  - OBJECTIVES: To describe the small area system developed in Finland. To illustrate
      the use of the system with analyses of incidence of lung cancer around an
      asbestos mine. To compare the performance of different spatial statistical models
      when applied to sparse data. METHODS: In the small area system, cancer and
      population data are available by sex, age, and socioeconomic status in adjacent
      "pixels", squares of size 0.5 km x 0.5 km. The study area was partitioned into
      sub-areas based on estimated exposure. The original data at the pixel level were
      used in a spatial random field model. For comparison, standardised incidence
      ratios were estimated, and full bayesian and empirical bayesian models were
      fitted to aggregated data. Incidence of lung cancer around a former asbestos mine
      was used as an illustration. RESULTS: The spatial random field model, which has
      been used in former small area studies, did not converge with present fine
      resolution data. The number of neighbouring pixels used in smoothing had to be
      enlarged, and informative distributions for hyperparameters were used to
      stabilise the unobserved random field. The ordered spatial random field model
      gave lower estimates than the Poisson model. When one of the three effects of
      area were fixed, the model gave similar estimates with a narrower interval than
      the Poisson model. CONCLUSIONS: The use of fine resolution data and socioeconomic
      status as a means of controlling for confounding related to lifestyle is useful
      when estimating risk of cancer around point sources. However, better statistical
      methods are needed for spatial modelling of fine resolution data.

PMID- 11303081
TI  - A case-referent study of cancer mortality among sulfate mill workers in Sweden.
AB  - OBJECTIVES: To investigate whether workers in Swedish sulfate mills have an
      increased risk of death from certain malignancies that have previously been
      linked to the pulping process. METHODS: Subjects of the study (n=2480) were men
      aged 40-75 at death during 1960-89 in the parishes surrounding four sulfate
      mills. Exposure assessment was based on information from the personnel files in
      the mills- 35% of the subjects were recognised there, and work categories were
      created. RESULTS: Among all sulfate mill workers, the odds ratio (OR) (90%
      confidence interval (90% CI)) for death from lung cancer was 1.6 (1.1 to 2.3),
      pleural mesotheliomas 9.5 (1.9 to 48), brain tumours 2.6 (1.2 to 5.3), and liver
      or biliary tract cancer 2.3 (1.0 to 5.2). There was an increased mortality from
      leukaemia among workers in the soda recovery plant (5.9 (2.6 to 13)) and
      bleaching plant and digester house (2.8 (1.0 to 7.5)). CONCLUSIONS: Sulfate mill
      workers were at increased risk of dying from lung cancer and pleural
      mesotheliomas, probably due to exposure to asbestos. Increased risks of brain
      tumours and cancers of the liver or biliary tract were also found but the
      aetiology is not obvious.

PMID- 11303082
TI  - Research priorities in occupational health in Italy.
AB  - OBJECTIVE: To find a broad consensus on research priorities and strategies in the
      field of occupational health and safety in Italy. METHODS: A two phase
      questionnaire survey was based on the Delphi technique previously described in
      other reports. 310 Occupational safety and health specialists (from universities
      and local health units) were given an open questionnaire (to identify three
      priority research areas). The data obtained from respondents (175, 56.4%) were
      then used to draw up a list of 27 priority topics grouped together into five
      macrosectors. Each of these was given a score ranging from 1 (of little
      importance) to 5 (extremely important). With the mean scores obtained from a
      total of 203 respondents (65.4%), it was possible to place the 27 topics in rank
      order according to a scale of priorities. RESULTS: Among the macrosectors, first
      place was given to the question of methodological approach to research in this
      field, and for individual topics, occupational carcinogenesis and quality in
      occupational medicine were ranked first and second, respectively. The question of
      exposure to low doses of environmental pollutants and multiple exposures ranked
      third among the priorities; the development of adequate and effective approaches
      and methods for worker education and participation in prevention was also
      perceived as being an important issue (fourth place). CONCLUSIONS: This study
      (the first of its kind in Italy) enabled us to achieve an adequate degree of
      consensus on research priorities related to the protection of occupational health
      and safety. Disparities in the mean scores of some of the issues identified
      overall as being research priorities, seem to be linked both to geographical area
      and to whether respondents worked in local health units or universities. This
      finding requires debate and further analysis.

PMID- 11303083
TI  - Occupational injuries in Italy: risk factors and long term trend (1951-98).
AB  - OBJECTIVES: Trends in the rates of total injuries and fatal accidents in the
      different sectors of Italian industries were explored during the period 1951-98.
      Causes and dynamics of injury were also studied for setting priorities for
      improving safety standards. METHODS: Data on occupational injuries from the
      National Organisation for Labour Injury Insurance were combined with data from
      the State Statistics Institute to highlight the interaction between the injury
      frequency index trend and the production cycle-that is, the evolution of
      industrial production throughout the years. Multiple regression with log
      transformed rates was adopted to model the trends of occupational fatalities for
      each industrial group. RESULTS: The ratios between the linked indices of injury
      frequency and industrial production showed a good correlation over the whole
      period. A general decline in injuries was found across all sectors, with values
      ranging from 79.86% in the energy group to 23.32% in the textile group. In
      analysing fatalities, the trend seemed to be more clearly decreasing than the
      trend of total injuries, including temporary and permanent disabilities; the
      fatalities showed an exponential decrease according to multiple regression, with
      an annual decline equal to 4.42%. CONCLUSIONS: The overall probability of
      industrial fatal accidents in Italy tended to decrease exponentially by year. The
      most effective actions in preventing injuries were directed towards fatal
      accidents. By analysing the rates of fatal accident in the different sectors,
      appropriate targets and priorities for increased strategies to prevent injuries
      can be suggested. The analysis of the dynamics and the material causes of
      injuries showed that still more consideration should be given to human and
      organisational factors.

PMID- 11303084
TI  - Consultative team to assess manual handling and reduce the risk of occupational
      injury.
AB  - OBJECTIVES: To describe the formation of a consultative team to assess the risk
      of manual handling in the workplace that started in October 1992 within the
      cleaning services department of a 600 bed hospital, and to evaluate the
      effectiveness of its recommendations in reducing the rate and severity (time lost
      and cost) of workers' compensation injury. METHODS: The consultative team
      identified, assessed, and recommended controls for manual handling and other
      injury risks. Data on injuries counted before and after implementation of the
      team's recommendations were obtained for the cleaning services study group, an
      orderly services comparison group, as well as cleaners from a peer hospital and
      for the State of Western Australia. Evaluation of the four groups was undertaken
      3 years after the end of the study period, to allow maturation of the costs of
      the claims (adjusted to July 1998 consumer price index) and hours lost from work.
      RESULTS: Statistical analysis showed that implementation of the recommendations
      significantly reduced numbers and rates of injury, but not the severity of
      injury, in the cleaning services study group. There was no difference in numbers
      or severity of injuries for the comparison groups before and after implementation
      of the recommendations. CONCLUSIONS: The recommendation of the consultative team
      can produce a meaningful and sustained reduction in rates of injury within an at
      risk population. The results support a consultative approach to reducing
      workplace injuries from manual handling. The team process has potential for
      application to occupational groups at risk of exposure to other types of hazards.

PMID- 11303085
TI  - Longitudinal study on work related and individual risk factors affecting
      radiating neck pain.
AB  - OBJECTIVES: To study the effects of work related and individual factors affecting
      radiating neck pain. METHODS: A longitudinal study was carried out with repeated
      measurements. A total of 5180 Finnish forest industry workers replied to a
      questionnaire survey in 1992 (response rate 75%). Response rates to follow up
      questionnaires in 1993, 1994, and 1995 were 83%, 77%, and 90%, respectively. The
      outcome variable was the number of days with radiating neck pain during the
      preceding 12 months with three levels (<8, 8-30, >30 days). The generalised
      estimating equations method was used to fit a marginal model and a transition
      model was used in a predictive analysis. RESULTS: Items showing associations with
      radiating neck pain in both analyses were sex, age, body mass index, smoking,
      duration of work with a hand above shoulder level, mental stress, and other
      musculoskeletal pains. In the transition model, radiating neck pain in a previous
      questionnaire was included in the model. Although it was a strong predictor, the
      variables already mentioned retained their significance. CONCLUSION: Programmes
      targeted to reduce physical load at work, mental stress, being overweight, and
      smoking could potentially prevent radiating neck pain.

PMID- 11303086
TI  - Agents, old and new, causing occupational asthma.

PMID- 11303087
TI  - Control of a genetic regulatory network by a selector gene.
AB  - The formation of many complex structures is controlled by a special class of
      transcription factors encoded by selector genes. It is shown that SCALLOPED, the
      DNA binding component of the selector protein complex for the Drosophila wing
      field, binds to and directly regulates the cis-regulatory elements of many
      individual target genes within the genetic regulatory network controlling wing
      development. Furthermore, combinations of binding sites for SCALLOPED and
      transcriptional effectors of signaling pathways are necessary and sufficient to
      specify wing-specific responses to different signaling pathways. The obligate
      integration of selector and signaling protein inputs on cis-regulatory DNA may be
      a general mechanism by which selector proteins control extensive genetic
      regulatory networks during development.

PMID- 11303088
TI  - Cultural responses to climate change during the late Holocene.
AB  - Modern complex societies exhibit marked resilience to interannual-to- decadal
      droughts, but cultural responses to multidecadal-to-multicentury droughts can
      only be addressed by integrating detailed archaeological and paleoclimatic
      records. Four case studies drawn from New and Old World civilizations document
      societal responses to prolonged drought, including population dislocations, urban
      abandonment, and state collapse. Further study of past cultural adaptations to
      persistent climate change may provide valuable perspective on possible responses
      of modern societies to future climate change.

PMID- 11303089
TI  - MgB2 superconducting thin films with a transition temperature of 39 kelvin.
AB  - We fabricated high-quality c axis-oriented epitaxial MgB2 thin films using a
      pulsed laser deposition technique. The thin films grown on (1 i 0 2) Al2O3
      substrates have a transition temperature of 39 kelvin. The critical current
      density in zero field is approximately 6 x 10(6) amperes per cubic centimeter at
      5 kelvin and approximately 3 x 10(5) amperes per cubic centimeter at 35 kelvin,
      which suggests that this compound has potential for electronic device
      applications, such as microwave devices and superconducting quantum interference
      devices. For the films deposited on Al2O3, x-ray diffraction patterns indicate a
      highly c axis-oriented crystal structure perpendicular to the substrate surface.

PMID- 11303090
TI  - The foot-and-mouth epidemic in Great Britain: pattern of spread and impact of
      interventions.
AB  - We present an analysis of the current foot-and-mouth disease epidemic in Great
      Britain over the first 2 months of the spread of the virus. The net transmission
      potential of the pathogen and the increasing impact of control measures are
      estimated over the course of the epidemic to date. These results are used to
      parameterize a mathematical model of disease transmission that captures the
      differing spatial contact patterns between farms before and after the imposition
      of movement restrictions. The model is used to make predictions of future
      incidence and to simulate the impact of additional control strategies. Hastening
      the slaughter of animals with suspected infection is predicted to slow the
      epidemic, but more drastic action, such as "ring" culling or vaccination around
      infection foci, is necessary for more rapid control. Culling is predicted to be
      more effective than vaccination.

PMID- 11303091
TI  - Object processing in the infant brain.

PMID- 11303092
TI  - Auditory spatial receptive fields created by multiplication.
AB  - Examples of multiplication by neurons or neural circuits are scarce, although
      many computational models use this basic operation. The owl's auditory system
      computes interaural time (ITD) and level (ILD) differences to create a two
      dimensional map of auditory space. Space-specific neurons are selective for
      combinations of ITD and ILD, which define, respectively, the horizontal and
      vertical dimensions of their receptive fields. A multiplication of separate
      postsynaptic potentials tuned to ITD and ILD, rather than an addition, can
      account for the subthreshold responses of these neurons to ITD-ILD pairs. Other
      nonlinear processes improve the spatial tuning of the spike output and reduce the
      fit to the multiplicative model.

PMID- 11303093
TI  - Josephson junctions with tunable weak links.
AB  - The electrical properties of organic molecular crystals, such as polyacenes or
      C60, can be tuned from insulating to superconducting by application of an
      electric field. By structuring the gate electrode of such a field-effect switch,
      the charge carrier density, and therefore also the superfluid density, can be
      modulated. Hence, weak links that behave like Josephson junctions can be
      fabricated between two superconducting regions. The coupling between the
      superconducting regions can be tuned and controlled over a wide range by the
      applied gate bias. Such devices might be used in superconducting circuits, and
      they are a useful scientific tool to study superconducting material parameters,
      such as the superconducting gap, as a function of carrier concentration or
      transition temperature.

PMID- 11303094
TI  - Single-molecule studies of heterogeneous dynamics in polymer melts near the glass
      transition.
AB  - Single-molecule spectroscopy was used to follow the orientation of a single probe
      molecule in a polymer film in real time. Broad spatially heterogeneous dynamics
      were observed on long time scales, which result from simple diffusive rotational
      motions on short time scales. This diffusive behavior persists for many rotations
      before the molecule's local environment changes to one characterized by a new
      time scale. This environmental exchange occurs instantaneously on the time scale
      of the experiment and may arise from large-scale collective motions. The
      distribution of exchange times for these environments was measured for several
      temperatures near the glass transition.

PMID- 11303095
TI  - Real-space imaging of nucleation and growth in colloidal crystallization.
AB  - Crystallization of concentrated colloidal suspensions was studied in real space
      with laser scanning confocal microscopy. Direct imaging in three dimensions
      allowed identification and observation of both nucleation and growth of
      crystalline regions, providing an experimental measure of properties of the
      nucleating crystallites. By following their evolution, we identified critical
      nuclei, determined nucleation rates, and measured the average surface tension of
      the crystal-liquid interface. The structure of the nuclei was the same as the
      bulk solid phase, random hexagonal close-packed, and their average shape was
      rather nonspherical, with rough rather than faceted surfaces.

PMID- 11303096
TI  - Capturing a photoexcited molecular structure through time-domain x-ray absorption
      fine structure.
AB  - The determination of the structure of transient molecules, such as photoexcited
      states, in disordered media (such as in solution) usually requires methods with
      high temporal resolution. The transient molecular structure of a reaction
      intermediate produced by photoexcitation of NiTPP-L2 (NiTPP,
      nickeltetraphenylporphyrin; L, piperidine) in solution was determined by x-ray
      absorption fine structure (XAFS) data obtained on a 14-nanosecond time scale from
      a third-generation synchrotron source. The XAFS measurements confirm that
      photoexcitation leads to the rapid removal of both axial ligands to produce a
      transient square-planar intermediate, NiTPP, with a lifetime of 28 nanoseconds.
      The transient structure of the photodissociated intermediate is nearly identical
      to that of the ground state NiTPP, suggesting that the intermediate adopts the
      same structure as the ground state in a noncoordinating solvent before it
      recombines with two ligands to form the more stable octahedrally coordinated
      NiTPP-L2.

PMID- 11303097
TI  - Using selective withdrawal to coat microparticles.
AB  - We report a method that uses the process of selective withdrawal of one fluid
      through a second immiscible fluid to coat small particles with polymer films.
      Fluid is withdrawn through a tube with its orifice slightly above a water-oil
      interface. Upon increasing the flow rate, there is a transition from a state
      where only oil is withdrawn to a state where the water, containing the particles
      to be coated and appropriate prepolymer reagents, is entrained in a thin spout
      along with the oil. The entrained particles eventually cause the spout interface
      to break, producing a thin coat of controllable thickness around each particle,
      which can be subsequently polymerized using chemical reagents, light, or heat.
      This method allows flexibility in the chemical composition and thickness of the
      conformal coatings.

PMID- 11303098
TI  - Anthropogenic warming of Earth's climate system.
AB  - We compared the temporal variability of the heat content of the world ocean, of
      the global atmosphere, and of components of Earth's cryosphere during the latter
      half of the 20th century. Each component has increased its heat content (the
      atmosphere and the ocean) or exhibited melting (the cryosphere). The estimated
      increase of observed global ocean heat content (over the depth range from 0 to
      3000 meters) between the 1950s and 1990s is at least one order of magnitude
      larger than the increase in heat content of any other component. Simulation
      results using an atmosphere-ocean general circulation model that includes
      estimates of the radiative effects of observed temporal variations in greenhouse
      gases, sulfate aerosols, solar irradiance, and volcanic aerosols over the past
      century agree with our observation-based estimate of the increase in ocean heat
      content. The results we present suggest that the observed increase in ocean heat
      content may largely be due to the increase of anthropogenic gases in Earth's
      atmosphere.

PMID- 11303099
TI  - Detection of anthropogenic climate change in the world's oceans.
AB  - Large-scale increases in the heat content of the world's oceans have been
      observed to occur over the last 45 years. The horizontal and temporal character
      of these changes has been closely replicated by the state-of-the-art Parallel
      Climate Model (PCM) forced by observed and estimated anthropogenic gases.
      Application of optimal detection methodology shows that the model-produced
      signals are indistinguishable from the observations at the 0.05 confidence level.
      Further, the chances of either the anthropogenic or observed signals being
      produced by the PCM as a result of natural, internal forcing alone are less than
      5%. This suggests that the observed ocean heat-content changes are consistent
      with those expected from anthropogenic forcing, which broadens the basis for
      claims that an anthropogenic signal has been detected in the global climate
      system. Additionally, the requirement that modeled ocean heat uptakes match
      observations puts a strong, new constraint on anthropogenically forced climate
      models. It is unknown if the current generation of climate models, other than the
      PCM, meet this constraint.

PMID- 11303100
TI  - Climate response to orbital forcing across the Oligocene-Miocene boundary.
AB  - Spectral analyses of an uninterrupted 5.5-million-year (My)-long chronology of
      late Oligocene-early Miocene climate and ocean carbon chemistry from two deep-sea
      cores recovered in the western equatorial Atlantic reveal variance concentrated
      at all Milankovitch frequencies. Exceptional spectral power in climate is
      recorded at the 406-thousand-year (ky) period eccentricity band over a 3.4
      million-year period [20 to 23.4 My ago (Ma)] as well as in the 125- and 95-ky
      bands over a 1.3-million-year period (21.7 to 23.0 Ma) of suspected low
      greenhouse gas levels. Moreover, a major transient glaciation at the epoch
      boundary ( approximately 23 Ma), Mi-1, corresponds with a rare orbital congruence
      involving obliquity and eccentricity. The anomaly, which consists of low
      amplitude variance in obliquity (a node) and a minimum in eccentricity, results
      in an extended period ( approximately 200 ky) of low seasonality orbits favorable
      to ice-sheet expansion on Antarctica.

PMID- 11303101
TI  - Molecular mechanisms of the biological clock in cultured fibroblasts.
AB  - In mammals, the central circadian pacemaker resides in the hypothalamic
      suprachiasmatic nucleus (SCN), but circadian oscillators also exist in peripheral
      tissues. Here, using wild-type and cryptochrome (mCry)-deficient cell lines
      derived from mCry mutant mice, we show that the peripheral oscillator in cultured
      fibroblasts is identical to the oscillator in the SCN in (i) temporal expression
      profiles of all known clock genes, (ii) the phase of the various mRNA rhythms
      (i.e., antiphase oscillation of Bmal1 and mPer genes), (iii) the delay between
      maximum mRNA levels and appearance of nuclear mPER1 and mPER2 protein, (iv) the
      inability to produce oscillations in the absence of functional mCry genes, and
      (v) the control of period length by mCRY proteins.

PMID- 11303102
TI  - Forecasting agriculturally driven global environmental change.
AB  - During the next 50 years, which is likely to be the final period of rapid
      agricultural expansion, demand for food by a wealthier and 50% larger global
      population will be a major driver of global environmental change. Should past
      dependences of the global environmental impacts of agriculture on human
      population and consumption continue, 10(9) hectares of natural ecosystems would
      be converted to agriculture by 2050. This would be accompanied by 2.4- to 2.7
      fold increases in nitrogen- and phosphorus-driven eutrophication of terrestrial,
      freshwater, and near-shore marine ecosystems, and comparable increases in
      pesticide use. This eutrophication and habitat destruction would cause
      unprecedented ecosystem simplification, loss of ecosystem services, and species
      extinctions. Significant scientific advances and regulatory, technological, and
      policy changes are needed to control the environmental impacts of agricultural
      expansion.

PMID- 11303103
TI  - Regulation of differentiation to the infective stage of the protozoan parasite
      Leishmania major by tetrahydrobiopterin.
AB  - A critical step in the infectious cycle of Leishmania is the differentiation of
      parasites within the sand fly vector to the highly infective metacyclic
      promastigote stage. Here, we establish tetrahydrobiopterin (H4B) levels as an
      important factor controlling the extent of metacyclogenesis. H4B levels decline
      substantially during normal development, and genetic or nutritional manipulations
      showed that low H4B caused elevated metacyclogenesis. Mutants lacking pteridine
      reductase 1 (PTR1) had low levels of H4B, remained infectious to mice, and
      induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine
      metabolism has relevance to the mechanism of Leishmania differentiation and the
      limitation of virulence during evolution.

PMID- 11303104
TI  - Functional specialization in rhesus monkey auditory cortex.
AB  - Neurons in the lateral belt areas of rhesus monkey auditory cortex prefer complex
      sounds to pure tones, but functional specializations of these multiple maps in
      the superior temporal region have not been determined. We tested the specificity
      of neurons in the lateral belt with species-specific communication calls
      presented at different azimuth positions. We found that neurons in the anterior
      belt are more selective for the type of call, whereas neurons in the caudal belt
      consistently show the greatest spatial selectivity. These results suggest that
      cortical processing of auditory spatial and pattern information is performed in
      specialized streams rather than one homogeneously distributed system.

PMID- 11303105
TI  - G protein betagamma subunit-mediated presynaptic inhibition: regulation of
      exocytotic fusion downstream of Ca2+ entry.
AB  - The nervous system can modulate neurotransmitter release by neurotransmitter
      activation of heterotrimeric GTP-binding protein (G protein)-coupled receptors.
      We found that microinjection of G protein betagamma subunits (Gbetagamma) mimics
      serotonin's inhibitory effect on neurotransmission. Release of free Gbetagamma
      was critical for this effect because a Gbetagamma scavenger blocked serotonin's
      effect. Gbetagamma had no effect on fast, action potential-evoked intracellular
      Ca2+ release that triggered neurotransmission. Inhibition of neurotransmitter
      release by serotonin was still seen after blockade of all classical Gbetagamma
      effector pathways. Thus, Gbetagamma blocked neurotransmitter release downstream
      of Ca2+ entry and may directly target the exocytotic fusion machinery at the
      presynaptic terminal.

PMID- 11303106
TI  - Two functional channels from primary visual cortex to dorsal visual cortical
      areas.
AB  - Relationships between the M and P retino-geniculo-cortical visual pathways and
      "dorsal" visual areas were investigated by measuring the sources of local
      excitatory input to individual neurons in layer 4B of primary visual cortex. We
      found that contributions of the M and P pathways to layer 4B neurons are
      dependent on cell type. Spiny stellate neurons receive strong M input through
      layer 4Calpha and no significant P input through layer 4Cbeta. In contrast,
      pyramidal neurons in layer 4B receive strong input from both layers 4Calpha and
      4Cbeta. These observations, along with evidence that direct input from layer 4B
      to area MT arises predominantly from spiny stellates, suggest that these
      different cell types constitute two functionally specialized subsystems.

PMID- 11303107
TI  - Themes in movement disorders research.

PMID- 11303108
TI  - Planning reaching and grasping movements: theoretical premises and practical
      implications.
AB  - This paper presents the background, premises, and results of a model of movement
      planning. The model's central claims are fourfold: (a) A task is defined by a set
      of prioritized requirements, or what we call a constraint hierarchy; (b) movement
      planning works first by specifying a goal posture and then by specifying a
      movement to that goal posture; (c) movements have characteristic forms; and (d)
      movements can be shaped through simultaneous performance of different movements,
      even by the same effector. We review the model and then speculate on its
      implications for clinical concerns, especially spasticity

PMID- 11303109
TI  - Planning reaching and grasping movements: the problem of obstacle avoidance.
AB  - In this article, we review a model of the movement-planning processes that people
      use for direct reaching, reaching around obstacles, and grasping, and we present
      observations of subjects' repeated movements of the hand to touch 2 target
      locations, circumventing an intervening obstacle. The model defines an obstacle
      as a posture that, if adopted, would intersect with any part of the environment
      (including the actor himself or herself). The model finds a trajectory that is
      likely to bring the end-effector to the target by means of a one-or two- stage
      planning process. Each stage exploits the principles of instance retrieval and
      instance generation. In the first stage, a goal posture is identified, and the
      trajectory of a direct transition to that posture is tested for collision. If the
      direct movement has no collision, the movement to the target is immediately
      executed in joint space. If, however, the direct movement is foreseen to result
      in a collision, a second planning stage is invoked. The second planing stage
      identifies a via posture, movement through which will probably avoid the
      collision. Movement to and from the via posture is then superimposed on the main
      movement to the target so that the combined movement reaches the target without
      colliding with intervening obstacles. We describe the details of instance
      retrieval and instance generation for each of these planning stages and compare
      the model's performance with the observed kinematics of direct movements as well
      as movements around an obstacle. Then we suggest how the model might contribute
      to the study of movements in people with motor disorders such as spastic
      hemiparesis.

PMID- 11303110
TI  - Planning reaching and grasping movements: simulating reduced movement
      capabilities in spastic hemiparesis.
AB  - In this paper we describe how a theory of posture-based motion planning recently
      applied to human grasping may contribute to the understanding of grasping
      pathology. The theory is implemented as a computer model rendered as a stick
      figure animation capable of generating realistic multi-joint grasping movements.
      As shown here, the model can also be used to simulate grasping movements whose
      kinematics resemble those of grasps performed by people with spastic hemiparesis.
      The simulations demonstrate effects of: (a) reduced ranges of motion of arm
      joints on the size of the reachable workspace, (b) awkward starting postures on
      the time course of the hand closing around an object, (c) increased costs of
      joint rotations on movement time, and (d) addition of noise to biphasic joint
      rotations on the low-velocity phase of wrist transport.

PMID- 11303111
TI  - Shoulder and hand displacements during hitting, reaching, and grasping movements
      in hemiparetic cerebral palsy.
AB  - In this study, we examined the degree and timing of shoulder displacements during
      hitting, reaching, and grasping movements performed by young adults with
      hemiparetic cerebral palsy. The participants performed unimanual and bimanual arm
      movements towards targets and objects of different sizes. On the basis of the
      assumption that shoulder displacement due to trunk translation and rotation is a
      successful adaptive reaction to reduced joint mobility in the affected arm, the
      fluency of hand displacements was expected to remain invariant under variations
      of shoulder displacement as is also the case in healthy participants. The results
      point in this direction. With respect to the timing of shoulder displacement,
      prior research suggested that hemiparetic movements can be characterized by
      inconsistent motion-timing patterns-that is, the timing of the of shoulder and
      hand-displacement onsets varied between trials. Therefore, the within-subject
      variability of the movement-onset asynchrony between hand and ipsilateral
      shoulder displacement was expected to be larger on the impaired side than on the
      unimpaired side. This prediction was not confirmed, which challenges these
      earlier conclusions. Additionally, we also examined the peak-velocity asynchrony
      of the hand and shoulder. Contrary to the onset asynchrony, the peak asynchrony
      varied between the hitting and reaching task and between the hitting and grasping
      task. For the reaching and grasping tasks, there were also significant
      differences between hands. Again, variability of the (peak-velocity) asynchrony
      was not significantly increased when comparing the impaired hand with the
      unimpaired hand. The results suggests that the hemiparetic participants were
      capable of flexibly recruiting and sequencing the various degrees of freedom of
      their impaired side required for successful task completion, albeit in different
      magnitudes and sequenced differently.

PMID- 11303112
TI  - Spatial interactions during bimanual coordination patterns: the effect of
      directional compatibility.
AB  - Whereas previous bimanual coordination research has predominantly focused on the
      constraining role of timing, the present study addressed the role of spatial
      (i.e., directional) constraints during the simultaneous production of equilateral
      triangles with both upper limbs. In addition to coordination modes in which
      mirror-image and isodirectional movements were performed (compatible patterns),
      new modes were tested in which the left limb lagged with respect to the right by
      one triangle side (non-compatible patterns). This resulted in the experimental
      manipulation of directional compatibility between the limbs. In addition,
      triangles with either horizontal or vertical orientations were to be drawn in
      order to assess the role of static images on movement production. Results
      supported the important role of directional constraints in bimanual coordination.
      Furthermore, triangles in vertical orientations (with a vertical symmetry axis,
      i.e., one apex pointing up) were drawn more successfully than those in horizontal
      orientations (with a horizontal symmetry axis, i.e., one apex pointing left or
      right), suggesting that the static aspects of a geometric form may affect
      movement dynamics. Finally, evidence suggested that cognitive processes related
      to integration of the submovements into a unified plan mediate the performance of
      new coordination patterns. The implications of the present finding for clinical
      populations are discussed

PMID- 11303113
TI  - The regulation of fine movements in patients with Charcot Marie Tooth, type Ia:
      some ideas about continuous adaptation.
AB  - The flexibility of the human motor system is remarkable. Even when parts of the
      system are damaged, the output often remains optimal or near optimal. The
      neuromotor system is designed to keep the output optimal by shifting between
      input sources. This capability is termed the principle of continuous adaptation.
      This article describes an experiment in which patients suffering from a
      hereditary motor and sensory neuropathy, type 1a (Charcot Marie Tooth disease,
      type 1a), had to perform fine motor movements. We examined whether they were able
      to regulate these movements in spite of the fact that the somatosensory input and
      motor output was substantially impaired as a result of the chronic, slowly
      progressing neuropathy. It was predicted that these patients were able to perform
      fine movements as long as the movements were well known and over-learned.
      Furthermore, it was predicted that these patients would compensate for the loss
      of somatosensory information by becoming more dependent on vision. A second
      prediction was that the quality of the motor performance would break down when
      these patients had to perform a novel motor pattern. The performance of the
      patients (n=10) was contrasted with the performance of 20 healthy subjects. The
      results indicated that the patients, indeed, were able to perform the over
      learned movements and that their performance deteriorated significantly when they
      had to perform a novel motor pattern. No indication, however, could be found for
      visual compensation.

PMID- 11303128
TI  - Mortality after appendectomy in Sweden, 1987-1996.
AB  - OBJECTIVE: To study mortality after appendectomy. SUMMARY BACKGROUND DATA: The
      management of patients with suspected appendicitis remains controversial, with
      advocates of early surgery as well as of expectant management. Mortality is not
      known. METHODS: The authors conducted a complete follow-up of deaths within 30
      days after all appendectomies in Sweden (population 8.9 million) during the years
      1987 to 1996 (n = 117,424) by register linkage. The case fatality rate (CFR) and
      the standardized mortality ratio (SMR) were analyzed by discharge diagnosis.
      RESULTS: The CFR was 2.44 per 1,000 appendectomies. It was strongly related to
      age (0.31 per 1,000 appendectomies at 0-9 years of age, decreasing to 0.07 at 20
      29 years, and reaching 164 among nonagenarians) and diagnosis at surgery (0.8 per
      1,000 appendectomies after nonperforated appendicitis, 5.1 after perforated
      appendicitis, 1.9 after appendectomies for nonsurgical abdominal pain, and 10.0
      for those with other diagnoses). The SMR showed a sevenfold excess rate of deaths
      after appendectomy compared with the general population. The relation to age was
      less marked (SMR of 44.4 at 0-9 years, decreasing to 2.4 in patients aged 20-29
      years. and reaching 8.1 in nonagenarians). The SMR was doubled after perforation
      compared with nonperforated appendicitis (6.5 and 3.5, respectively). Nonsurgical
      abdominal pain and other diagnoses were associated with a high excess rate of
      deaths (9.1 and 14.9, respectively). The most common causes of deaths were
      appendicitis, ischemic heart diseases and tumors, followed by gastrointestinal
      diseases. CONCLUSIONS: The CFR after appendectomy is high in elderly patients.
      The excess rate of death for patients with nonperforated appendicitis and
      nonsurgical abdominal pain suggests that the deaths may partly be caused by the
      surgical trauma. Increased diagnostic efforts rather than urgent appendectomy are
      therefore warranted among frail patients with an equivocal diagnosis of
      appendicitis.

PMID- 11303129
TI  - Appendicitis in Sweden: quality results.

PMID- 11303131
TI  - Surgical technique for right lobe adult living donor liver transplantation
      without venovenous bypass or portocaval shunting and with duct-to-duct biliary
      reconstruction.
AB  - OBJECTIVE: To report the authors' experience with adult living donor liver
      transplantation (ALDLT) without venovenous bypass and to describe modifications
      that will allow for a direct duct-to-duct biliary reconstruction. SUMMARY
      BACKGROUND DATA: Adult living donor liver transplantation is being evaluated as a
      method to alleviate the organ shortage. Descriptions of the procedure have
      emphasized the use of venovenous bypass, portocaval decompression, and the
      mandatory use of a Roux-en-Y biliary enteric anastomosis. The authors describe a
      technique for ALDLT without venovenous bypass, portocaval decompression, or caval
      clamping in 11 recipients and describe the modifications to the procedure that
      may allow a duct-to-duct biliary reconstruction in certain cases. METHODS:
      Between March 1999 and March 2000, 11 ALDLTs were performed at the authors'
      institution. All procedures were performed without venovenous bypass, portocaval
      decompression, or caval clamping. After a modification to the procedure, five of
      the last six recipients underwent biliary reconstruction with a direct duct-to
      duct anastomosis. Data regarding donor, recipient, and graft survival,
      complications, and graft function were collected. RESULTS: Recipients comprised
      five women and six men, mean age 48 years. Donors comprised five women and six
      men, mean age 36.5 years. Donor to recipient relationships included sibling,
      spouse, son, and daughter. Indications for transplantation were hepatitis C,
      hepatitis C with hepatocellular carcinoma, primary biliary cirrhosis, primary
      sclerosing cholangitis, ethanol, and cryptogenic. No case required venovenous
      bypass or portocaval shunting. The right hepatic vein of the donor graft was
      anastomosed to the confluence of the left and middle hepatic veins in all cases.
      All donors are alive and well, with no adverse complications reported. Recipient
      and graft survival rates were 91% and 82%, respectively, for ALDLT versus 92% and
      92% for recipients of cadaveric organs during the same time period. One recipient
      died of multiple organ failure and sepsis. Biliary reconstruction was performed
      by Roux-en-Y hepaticojejunostomy in the six cases. In five of the last six
      recipients, direct duct-to-duct biliary reconstruction with a T tube was used. No
      anastomotic leaks or strictures occurred in the patients undergoing duct-to-duct
      reconstruction. CONCLUSIONS: Adult living donor liver transplantation can be
      performed safely and may help alleviate the organ shortage. Neither venovenous
      bypass nor portocaval shunting is necessary to perform the procedure, and
      modifications to both the donor and recipient hepatectomy procedures may allow
      biliary reconstruction to be performed by a direct duct-to-duct anastomosis in
      selected cases.

PMID- 11303132
TI  - Denervated stomach as an esophageal substitute recovers intraluminal acidity with
      time.
AB  - OBJECTIVE: To determine whether the denervated stomach as an esophageal
      substitute recovers normal intraluminal acidity with time. SUMMARY BACKGROUND
      DATA: Bilateral truncal vagotomy to the stomach as an esophageal substitute
      reduces both gastric acid production and antral motility, but a spontaneous motor
      recovery process takes place over years. METHODS: Intraluminal gastric pH and
      bile were monitored during a 24-hour period 1 to 195 months after transthoracic
      elevation of the stomach as esophageal replacement in 91 and 76 patients,
      respectively. Nine patients underwent a second gastric pH monitoring after a 3
      year period. The percentages of time that the gastric pH was less than 2 and bile
      absorbance exceeded 0.25 were calculated in reference to values from 25 healthy
      volunteers. Eighty-nine upper gastrointestinal endoscopies were performed in 83
      patients. Patients were divided into three groups depending on length of follow
      up: group 1, less than 1 year; group 2, 1 to 3 years; group 3, more than 3 years.
      RESULTS: The prevalence of a normal gastric pH profile was 32.3% in group 1,
      81.5% in group 2, and 97.6% in group 3. The percentage of time that the gastric
      pH was less than 2 increased from group 1 (27.3%) to group 2 (56.1%) and group 3
      (70.5%), parallel to an increase in the prevalence of cervical heartburn and
      esophagitis. The percentage of time that the gastric pH was less than 2 increased
      from 28.7% to 81.2% in the nine patients investigated twice. Exposure of the
      gastric mucosa to bile was 12.8% in patients with a high gastric pH profile
      versus 19.3% in those with normal acidity. In the esophageal remnant in six
      patients, Barrett's metaplasia developed, intestinal (n = 2) or gastric (n = 4)
      in type. CONCLUSIONS: Early after vagotomy, intraluminal gastric acidity is
      reduced in two thirds of patients, but the stomach recovers a normal intraluminal
      pH profile with time, so that in more than one third of patients, disabling
      cervical heartburn and esophagitis develop. The potential for the development of
      Barrett's metaplasia in the esophageal remnant brings into question the use of
      the stomach as an esophageal substitute in benign and early neoplastic disease.

PMID- 11303133
TI  - Ex vivo sentinel node mapping in carcinoma of the colon and rectum.
AB  - OBJECTIVE: Increasing evidence supports that the sentinel node (SN) is at
      greatest risk for harboring metastatic disease. This study describes a novel
      technique to identify the SN in colorectal carcinoma. METHODS: Within 30 minutes
      of resection, colorectal specimens were injected submucosally with isosulfan blue
      in four quadrants. Blue lymphatic channels were identified in the mesentery and
      followed to the blue-stained SN(s), which were then harvested. The specimen was
      fixed in formalin and subsequently analyzed in the usual fashion. Blue-stained
      nodes that were negative by hematoxylin and eosin staining were further analyzed
      by immunohistochemical staining. RESULTS: During a 6-month period, 26 patients
      with adenocarcinoma of the colon and rectum undergoing routine resection were
      studied. There were 18 men and 8 women ranging in age from 29 to 86 years (median
      66). Blue-stained SNs were identified in 24 of 26 specimens. The mean number of
      SNs identified per patient was 2.8 +/- 1.6. Seventy-three SNs were identified
      from a total of 479 lymph nodes harvested. The mean number of nodes identified
      per patient was 18.4 +/-7. A total of 67 lymph nodes in 12 patients were
      identified by hematoxylin and eosin staining to have evidence of metastatic
      disease. Fourteen (20%) of these nodes in six patients were stained blue.
      However, with immunohistochemical staining, only one blue node did not have
      evidence of metastatic tumor in a lymphatic basin with tumor present. Four
      patients (29%) whose lymphatic basins were negative by hematoxylin and eosin
      staining were upstaged by immunohistochemical staining of the SN. CONCLUSIONS: Ex
      vivo mapping of the colon and rectum is technically feasible and may provide a
      useful approach to the ultrastaging of colorectal carcinoma.

PMID- 11303134
TI  - Budd-Chiari syndrome: current management options.
AB  - OBJECTIVE: To assess the outcomes of current treatment strategies for Budd-Chiari
      syndrome. SUMMARY BACKGROUND DATA: Budd-Chiari syndrome, occlusion or obstruction
      of hepatic venous outflow, is a disease traditionally managed by portal or
      mesenteric-systemic shunting. The development of other treatment options, such as
      catheter-directed thrombolysis, transjugular portosystemic shunting (TIPS), and
      liver transplantation, has expanded the therapeutic algorithm. METHODS: The
      authors reviewed the medical records of all patients diagnosed with Budd-Chiari
      syndrome at the Johns Hopkins Hospital during the past 20 years. RESULTS: A total
      of 54 patients were identified: 13 (24%) male patients and 41 (76%) female
      patients, ranging in age from 2 to 76 years (median 33 years). Twenty-one (39%)
      had polycythemia vera, 3 (5.6%) used estrogens, 11 (20%) had a myeloproliferative
      or coagulation disorder, and in 7 (13%) the cause remained unknown. Forty-three
      patients were treated with surgical shunting, 24 mesocaval and 19 mesoatrial.
      Actuarial survival rates at 1, 3, and 5 years after shunting were 83%, 78%, and
      75%, respectively. Of 33 patients surviving more than 4 years, 28 (85%) had
      relief of clinical symptoms. Five patients required shunt revision and eight had
      radiologic procedures to maintain shunt patency. Primary and secondary shunt
      patency rates were 46% and 69% respectively for mesoatrial shunts and 70% and 85%
      respectively for mesocaval shunts. Clot lysis was successful as primary treatment
      in seven patients. TIPS was performed in three patients, one after a failed
      mesocaval shunt. During an average of 4 years of follow-up, these patients
      required multiple procedures to maintain TIPS patency. Six patients underwent
      liver transplantation. Of these, three had previous shunt procedures. Five of the
      transplant recipients are alive with follow-up of 2 to 9 years (median 6).
      CONCLUSIONS: Both shunting and transplantation can result in a 5-year survival
      rate of at least 75%, and other treatment modalities may be appropriate for
      highly selected patients. Optimal management requires that treatment be directed
      by the predominant clinical symptom (liver failure or portal hypertension) and
      anatomical considerations and be tempered by careful assessment of surgical risk.

PMID- 11303130
TI  - Lessons learned from more than 1,000 pancreas transplants at a single
      institution.
AB  - OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients
      according to risk factors and the surgical techniques and immunosuppressive
      protocols that evolved during a 33-year period at a single institution. SUMMARY
      BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high
      incidence of management problems and secondary complications. Clinical pancreas
      transplantation began at the University of Minnesota in 1966, initially with a
      high failure rate, but outcome improved in parallel with other organ transplants.
      The authors retrospectively analyzed the factors associated with the increased
      success rate of pancreas transplants. METHODS: From December 16, 1966, to March
      31, 2000, the authors performed 1,194 pancreas transplants (111 from living
      donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1
      simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK)
      transplants; and 291 pancreas transplants alone (PTA). The analyses were divided
      into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n
      = 148), transition to cyclosporine for immunosuppression, multiple duct
      management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986
      to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder
      drainage for graft duct management, and primarily triple therapy (cyclosporine,
      azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to
      1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to
      2000 (n = 275), use of daclizumab for induction immunosuppression, primarily
      enteric drainage for SPK transplants, pretransplant immunosuppression in
      candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft
      functional (insulin-independence) survival rates at 1 year by category and era
      were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85%
      and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61)
      versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and
      98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n =
      30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%,
      respectively. In eras 3 and 4 combined for primary cadaver SPK transplants,
      pancreas graft survival rates were significantly higher with bladder drainage (n
      = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03).
      Increasing recipient age had an adverse effect on outcome only in SPK recipients.
      Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a
      pretransplant myocardial infarction and 40% had a coronary artery bypass); those
      with no vascular disease had significantly higher patient and graft survival
      rates in the SPK and PAK categories. Living donor segmental pancreas transplants
      were associated with higher technically successful graft survival rates in each
      era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and
      4. Diabetic secondary complications were ameliorated in some recipients, and
      quality of life studies showed significant gains after the transplant in all
      recipient categories. CONCLUSIONS: Patient and graft survival rates have
      significantly improved over time as surgical techniques and immunosuppressive
      protocols have evolved. Eventually, islet transplants will replace pancreas
      transplants for suitable candidates, but currently pancreas transplants can be
      applied and should be an option at all stages of diabetes. Early transplants are
      preferable for labile diabetes, but even patients with advanced complications can
      benefit.

PMID- 11303135
TI  - Reticuloendothelial system blockade promotes progression from mild to severe
      acute pancreatitis in the opossum.
AB  - OBJECTIVE: To examine the relation between hepatic reticuloendothelial system
      (RES) dysfunction and the development of acute biliary pancreatitis. In an
      opossum model, the authors tested the hypothesis that RES blockade can turn the
      mild pancreatitis seen after pancreatic duct obstruction (PDO) into the severe
      form. SUMMARY BACKGROUND DATA: Biliary obstruction is considered the decisive
      event in gallstone pancreatitis. Suppression of the RES occurs during biliary
      obstruction. METHODS: Eighteen opossums were placed into three groups of six
      animals each: group A, RES blockade with lambda-carrageenan; group B, PDO; and
      group C, PDO and RES blockade with carrageenan. The severity of pancreatitis was
      evaluated by enzyme serum levels and percentage of pancreatic tissue necrosis.
      RES capacity was measured by dynamic liver scintigraphy, and hepatic blood flow
      was documented using the hydrogen clearance technique. RESULTS: No changes in
      hepatic blood flow occurred in groups A to C. RES capacity was suppressed in
      groups A and C; in group B, RES function remained unchanged. In group A, amylase
      and lipase levels remained normal, 3 +/- 1.9% of pancreatic tissue were necrotic.
      The animals in group B developed mild edematous pancreatitis with an increase in
      amylase and lipase levels and 15 +/- 10% of pancreatic necrosis. In group C,
      amylase and lipase increased significantly and histology revealed severe
      necrotizing pancreatitis, with 72 +/- 11% of necrotic areas. CONCLUSIONS:
      Artificial RES blockade can promote the progression from mild pancreatitis as
      observed after PDO to the severe necrotizing form of the disease. Thus, RES
      dysfunction resulting from biliary obstruction might be an important cofactor in
      the pathogenesis of bile-induced pancreatitis.

PMID- 11303136
TI  - Prospective comparison of stereotactic core biopsy and surgical excision as
      diagnostic procedures for breast cancer patients.
AB  - OBJECTIVE: To determine whether stereotactic core biopsy (SCNB) is the diagnostic
      method of choice for all mammographic abnormalities requiring tissue sampling.
      SUMMARY BACKGROUND DATA: Stereotactic core needle biopsy decreases the cost of
      diagnosis, but its impact on the number of surgical procedures needed to complete
      local therapy has not been studied in a large, unselected patient population.
      METHODS: A total of 1,852 mammographic abnormalities in 1,550 consecutive
      patients were prospectively categorized for level of cancer risk and underwent
      SCNB or diagnostic needle localization and surgical excision. Diagnosis, type of
      cancer surgery, and number of surgical procedures to complete local therapy were
      obtained from surgical and pathology databases. RESULTS: The malignancy rate was
      24%. Surgical biopsy patients were older, more likely to have cancer, and more
      likely to be treated with breast-conserving therapy than those in the SCNB group.
      For all types of lesions, regardless of degree of suspicion, patients diagnosed
      by SCNB were almost three times more likely to have one surgical procedure.
      However, for patients treated with lumpectomy alone, the number of surgical
      procedures and the rate of negative margins did not differ between groups.
      CONCLUSIONS: Stereotactic core needle biopsy is the diagnostic procedure of
      choice for most mammographic abnormalities. However, for patients undergoing
      lumpectomy without axillary surgery, it is an extra invasive procedure that does
      not facilitate obtaining negative margins.

PMID- 11303137
TI  - Double-blind placebo-controlled trial of fluconazole to prevent candidal
      infections in critically ill surgical patients.
AB  - OBJECTIVE: To evaluate the prophylactic use of enteral fluconazole to prevent
      invasive candidal infections in critically ill surgical patients. SUMMARY
      BACKGROUND DATA: Invasive fungal infections are increasingly common in the
      critically ill, especially in surgical patients. Although fungal prophylaxis has
      been proven effective in certain high-risk patients such as bone marrow
      transplant patients, few studies have focused on surgical patients and prevention
      of fungal infection. METHODS: The authors conducted a prospective, randomized,
      placebo-controlled trial in a single-center, tertiary care surgical intensive
      care unit (ICU). A total of 260 critically ill surgical patients with a length of
      ICU stay of at least 3 days were randomly assigned to receive either enteral
      fluconazole 400 mg or placebo per day during their stay in the surgical ICU at
      Johns Hopkins Hospital. RESULTS: The primary end point was the time to occurrence
      of fungal infection during the surgical ICU stay, with planned secondary analysis
      of patients "on-therapy" and alternate definitions of fungal infections. In a
      time-to-event analysis, the risk of candidal infection in patients receiving
      fluconazole was significantly less than the risk in patients receiving placebo.
      After adjusting for potentially confounding effects of the Acute Physiology and
      Chronic Health Evaluation (APACHE) III score, days to first dose, and fungal
      colonization at enrollment, the risk of fungal infection was reduced by 55% in
      the fluconazole group. No difference in death rate was observed between patients
      receiving fluconazole and those receiving placebo. CONCLUSIONS: Enteral
      fluconazole safely and effectively decreased the incidence of fungal infections
      in high-risk, critically ill surgical patients.

PMID- 11303138
TI  - Impact of bloodstream infection on outcomes among infected surgical inpatients.
AB  - OBJECTIVE: To assess the importance of bloodstream infection (BSI) to outcomes
      among infected surgical patients. BACKGROUND: Bloodstream infection complicating
      infection is thought to connote a more serious condition compared with a primary
      infection alone. The authors recently reported, however, that BSI does not alter
      outcomes with central venous catheter colonization in the presence of sepsis. The
      significance of BSI with other infections has been incompletely evaluated.
      METHODS: Data on all episodes of infection among surgical patients were collected
      prospectively during a 38-month period at a single hospital, then analyzed
      retrospectively to determine the independent prognostic value of BSI for all
      infections by logistic regression analysis, and for abdominal infections and
      pneumonia using matched control groups. RESULTS: During the study period, 2,076
      episodes of infection occurred, including 363 with BSI. Patients with BSI had a
      greater severity of illness and a greater death rate. After logistic regression,
      however, BSI did not independently predict death. After matching patients with
      abdominal infections and pneumonia with BSI to patients without BSI but with a
      similar site of infection, severity of illness, age, and causative organism, no
      difference in outcome was seen. CONCLUSIONS: Bloodstream infection is associated
      with critical illness and death but appears to be a marker of severe primary
      disease rather than an independent predictor of outcome.

PMID- 11303140
TI  - Split-liver transplantation for two adult recipients: feasibility and long-term
      outcomes.
AB  - OBJECTIVE: To identify the outcomes and risks of split-liver transplantation
      (SLT) for two adult recipients to determine the feasibility of more widespread
      use of this procedure to increase the graft pool for adults. SUMMARY BACKGROUND
      DATA: The shortage of cadaver liver grafts for adults is increasing. Using livers
      from donors defined as optimal, the authors have been developing techniques for
      SLT for two adult recipients at their center. METHODS: From July 1993 to December
      1999, 34 adults have undergone SLT with grafts from optimal donors prepared by ex
      situ split (n = 30) or in situ split (n = 4), and 88 adults received optimal
      whole-liver grafts that were not split. Four split-grafts were transplanted at
      other centers. The outcomes of transplantation with right and left split-liver
      grafts were compared with those of whole-liver transplants. The main end points
      were patient and graft survival at 1 and 2 years and the incidence and types of
      complications. RESULTS: For whole-liver, right and left split-liver grafts,
      respectively, patient survival rates were 88%, 74%, and 88% at 1 year and 85%,
      74%, and 64% at 2 years. Graft survival rates were 88%, 74%, and 75% at 1 year
      and 85%, 74%, and 43% at 2 years. Patient survival was adversely affected by
      graft steatosis and recipients inpatient status before transplantation. Graft
      survival was adversely affected by steatosis and a graft-to-recipient body weight
      ratio of less than 1%. Primary nonfunction occurred in three left split-liver
      grafts. The rates of arterial (6%) and biliary (22%) complications were similar
      to published data from conventional transplantation for an adult and a child. SLT
      for two adults increased the number of recipients by 62% compared with whole
      liver transplantation and was logistically possible in 16 of the 104 (15%)
      optimal cadaver donors. CONCLUSIONS: Split-liver transplantation for two adults
      is technically feasible. Outcomes and complication rates can be improved by rigid
      selection criteria for donors and recipients, particularly for the smaller left
      graft, and possibly also by in situ splitting in cadaver donors. Wider use will
      require changes in the procedures for graft allocation and coordination between
      centers experienced in the techniques.

PMID- 11303139
TI  - Anabolic effects of oxandrolone after severe burn.
AB  - OBJECTIVE: To explore the hypothesis that oxandrolone may reverse muscle
      catabolism in cachectic, critically ill pediatric burn patients. SUMMARY
      BACKGROUND DATA: Severe burn causes exaggerated muscle protein catabolism,
      contributing to weakness and delayed healing. Oxandrolone is an anabolic steroid
      that has been used in cachectic hepatitis and AIDS patients. METHODS: Fourteen
      severely burned children were enrolled during a 5-month period in a prospective
      cohort analytic study. There was a prolonged delay in the arrival of these
      patients to the burn unit for definitive care. This neglect of skin grafting and
      nutritional support resulted in critically ill children with significant
      malnutrition. On arrival, all patients underwent excision and skin grafting and
      received similar clinical care. Subjects were studied 5 to 7 days after
      admission, and again after 1 week of oxandrolone treatment at 0.1 mg/kg by mouth
      twice daily or no pharmacologic treatment. Muscle protein kinetics were derived
      from femoral arterial and venous blood samples and vastus lateralis muscle
      biopsies during a stable isotope infusion. RESULTS: Control and oxandrolone
      subjects were similar in age, weight, and percentage of body surface area burned.
      Muscle protein net balance decreased in controls and improved in the oxandrolone
      group. The improvement in the oxandrolone group was associated with increased
      protein synthesis efficiency. Muscle protein breakdown was unchanged.
      CONCLUSIONS: In burn victims, oxandrolone improves muscle protein metabolism
      through enhanced protein synthesis efficiency. These findings suggest the
      efficacy of oxandrolone in impeding muscle protein catabolism in cachectic,
      critically injured children.

PMID- 11303141
TI  - Small graft for living donor liver transplantation.
AB  - OBJECTIVE: To evaluate the impact of graft size on recipients in living donor
      liver transplantation (LDLT) to establish a clinical guideline for the minimum
      requirement. SUMMARY BACKGROUND DATA: Although the minimum graft size required
      for LDLT has been reported to be 30% to 40% of graft volume (GV)/standard liver
      volume (SLV), the safety limit of the graft size was unknown. METHODS: A total of
      33 cases of LDLT, excluding auxiliary transplantation, were reviewed with a
      minimum observation period of 4 months. The 33 patients were divided into three
      groups according to GV/SLV: medium-size graft group, small-size graft group, and
      extra-small graft group. The effect of GV/SLV on graft function, graft
      regeneration, and survival was evaluated. RESULTS: The overall patient survival
      rate was 94% at a mean follow-up of 15 months with a minimum observation period
      of 4 months. There were no statistically significant differences in postoperative
      bilirubin clearance, alanine aminotransferase, prothrombin time, and frequency of
      postoperative complications among the three groups. One week after
      transplantation, the regeneration rate (GV at 1 week/harvested GV) in the extra
      small and small groups was significantly higher than that of the medium group.
      The graft and patient survival rates were both 100% in the extra-small group, 75%
      and 88% in the small group, and 90% and 95% in the medium group. CONCLUSIONS:
      Small-for-size grafts less than 30% of SLV can be used with careful
      intraoperative and postoperative management until the grafts regenerate.

PMID- 11303142
TI  - Energy metabolism of infants and children with systemic inflammatory response
      syndrome and sepsis.
AB  - OBJECTIVE: To evaluate whether critically ill children with systemic inflammatory
      response syndrome (SIRS) or sepsis have altered resting energy expenditure (REE)
      and substrate utilization. SUMMARY BACKGROUND DATA: Studies in adults with sepsis
      have shown increased energy expenditure and mobilization of endogenous fat. In
      infants and children, energy metabolism and substrate utilization during sepsis
      have not been characterized. METHODS: Metabolic studies were performed in 21
      critically ill children with SIRS or sepsis. Twenty-one stable control children,
      matched for weight, were also studied. Seven patients required inotropic support
      and 17 received mechanical ventilation. Fifteen patients with SIRS had evidence
      of bacterial, fungal, or viral infection and were considered septic. Respiratory
      gas exchange was measured by computerized indirect calorimetry for 1 to 2 hours
      continuously. RESULTS: The REE of patients with SIRS or sepsis was not different
      from that of controls. Similarly, there were no differences in carbon dioxide
      production and oxygen consumption. Resting energy metabolism was not different
      between patients with SIRS and patients with sepsis. In addition, the presence of
      low platelet count or inotropic support did not affect resting energy metabolism.
      The median respiratory quotient of patients with SIRS or sepsis was 0.88 (range
      0.75-1.12), indicating mixed utilization of fat and carbohydrate; this was not
      significantly different from that of controls. The Pediatric Risk of Mortality
      Score was not significantly correlated with REE or respiratory quotient.
      CONCLUSIONS: The energy requirements of children with SIRS or sepsis are not
      increased. Their resting metabolism is based on both carbohydrate and fat
      utilization. The authors speculate that these children divert the energy for
      growth into recovery processes.

PMID- 11303143
TI  - Injury to the superior laryngeal branch of the vagus during thyroidectomy: lesson
      or myth?
AB  - OBJECTIVE: To examine the historical evidence that the thyroidectomy performed on
      operatic soprano Amelita Galli-Curci was responsible for the abrupt termination
      of her career. SUMMARY BACKGROUND DATA: The superior laryngeal branch of the
      vagus nerve may be injured during thyroidectomy, producing vocal defects more
      subtle than those found after recurrent nerve injury. It is widely believed that
      Galli-Curci suffered superior laryngeal nerve injury during her thyroidectomy by
      Arnold Kegel, MD, in 1935, resulting in the termination of her career. METHODS:
      The authors examined contemporary press reviews after surgery, conducted
      interviews with colleagues and relatives of the surgeon, and compared the career
      of Galli-Curci with that of other singers. RESULTS: Evidence against the
      prevailing view is to be found in the fact that she continued to perform
      acceptably after surgery, her continued friendly relationship with the surgeon
      for years afterward, the absence of the typical effects of superior laryngeal
      nerve injury, and the presence of other explanations for the gradual decline in
      her vocal abilities (documentation of deterioration before surgery, physiologic
      changes in the larynx comparable to those found in most other famous sopranos who
      retire at about the same age or earlier, and the possible development of
      myxedema). CONCLUSIONS: The story should no longer be perpetuated in surgical
      textbooks and papers.

PMID- 11303144
TI  - Aging and proinflammatory cytokines.
AB  - Aging is associated with increased inflammatory activity reflected by increased
      circulating levels of TNF-alpha, IL-6, cytokine antagonists and acute phase
      proteins in vivo. Epidemiologic studies suggest that chronic low-grade
      inflammation in aging promotes an atherogenic profile and is related to age
      associated disorders (eg, Alzheimer disease, atherosclerosis, type 2 diabetes,
      etc.) and enhanced mortality risk. Accordingly, a dysregulated production of
      inflammatory cytokines has an important role in the process of aging. Studies of
      age-related differences in the production of proinflammatory cytokines in
      response to acute stimulations in vitro have yielded inconsistent results.
      However, in vivo infectious models show delayed termination of inflammatory
      activity and a prolonged fever response in elderly humans, suggesting that the
      acute phase response is altered in aging. However, a causal relation between the
      acute phase response and the increased mortality because of bacterial infections
      in older patients remains to be demonstrated.

PMID- 11303145
TI  - Exercise and interleukin-6.
AB  - Strenuous exercise induces increased levels in a number of pro-and anti
      inflammatory cytokines, natural occurring cytokine inhibitors, and chemokines.
      Thus, increased plasma levels of tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL
      8, and macrophage inflammatory protein (MIP)-1 are found after strenuous
      exercise. The concentration of IL-6 increases as much as 100-fold after a
      marathon race. It has recently been demonstrated that IL-6 is produced locally in
      contracting skeletal muscles and that the net release from the muscle can account
      for the exercise-induced increase in arterial concentration. Larger amounts of IL
      6 are produced in response to exercise than any other cytokine, IL-6 is produced
      locally in the skeletal muscle in response to exercise, and IL-6 is known to
      induce hepatic glucose output and to induce lipolysis. These facts indicate that
      IL-6 may represent an important link between contracting skeletal muscles and
      exercise-related metabolic changes.

PMID- 11303146
TI  - Progress in clinical application of use of progenitor cells expanded with
      hematopoietic growth factors.
AB  - The ability to isolate and expand the cells capable of reconstituting
      hematopoiesis and immunity holds great promise to improve the outcomes of
      patients treated with autologous and allogeneic transplantation. The morbidity
      caused by prolonged neutropenia resulting from myeloablative therapy in the
      transplant setting leaves patients at risk to develop serious infections.
      Peripheral blood progenitor cells (PBPC) have supplanted bone marrow in
      autologous and allogeneic transplantation as a source of hematopoietic
      reconstitution mainly because of a reduction in the duration of neutropenia.
      Regardless, neutrophil recovery times continue to range between 7 to 10 days and
      platelet recovery times range between 12 to 24 days, after infusion of PBPC.
      Thus, ex vivo culture of PBPC has been evaluated for the purpose of providing a
      larger number of hematopoietic cells intended to accelerate the rate of recovery
      after myeloablative therapy. Moreover, expansion of alternative hematopoietic
      stem cell sources, including umbilical cord blood, has been tested in clinical
      trials.

PMID- 11303147
TI  - Role of hematopoietic growth factors/flt3 ligand in expansion and regulation of
      dendritic cells.
AB  - Dendritic cells (DCs) are hematopoietic cells that initiate immune responses by
      presenting antigen to T cells. Granulocyte-macrophage colony-stimulating factor
      (GM-CSF) is a primary growth factor for DCs in vitro, but recently it was
      recognized that other factors including flt3 ligand (FL) and G-CSF expand various
      DC subsets in vivo. DCs undergo a complex series of maturation and activation
      steps after they acquire antigen and before they can activate resting T cells. In
      addition, they must traffic to T-cell-rich areas of lymph nodes (LN) to achieve
      this. Each of these steps is tightly regulated, and in the last year progress has
      been made in identifying some of the key molecules involved in each of these
      steps. This progress will further the efforts underway to develop DCs as vaccine
      adjuvants.

PMID- 11303148
TI  - Safety of granulocyte colony-stimulating factor in normal donors.
AB  - Granulocyte colony-stimulating factor (G-CSF), which is widely used to mobilize
      peripheral blood stem cells (PBSC) from normal donors, has led to the use of PBSC
      as a major alternative to bone marrow for patients undergoing allogeneic
      transplants. Safety issues related to the administration of G-CSF to normal
      donors, however, are still under study. The short-term effects after G-CSF
      administration are well known and manageable. G-CSF induces a hypercoagulable
      state, which may predispose certain donors to thrombotic complications. A dose of
      10 microg/kg/d for 5 days has been recommended for routine clinical use, but the
      optimal dose and schedule for PBSC collection are still being defined. Small
      studies to date have shown no late effects of G-CSF administration but there is
      insufficient information regarding any long-term adverse effects or risks.
      Although the administration of G-CSF to normal donors for PBSC collection appears
      safe, longer follow-up is required.

PMID- 11303149
TI  - Granulocyte transfusion therapy: update on potential clinical applications.
AB  - The clinical usefulness of granulocyte transfusions for treatment or prevention
      of life-threatening bacterial and fungal infections remains controversial.
      Clinical benefit has long been limited by insufficient donor stimulation regimens
      and suboptimal leukapheresis techniques. Methodologic progress, in particular
      mobilization of neutrophils in healthy donors by administration of G-CSF, has
      significantly enhanced leukapheresis yields. A newly published study indicates
      that unrelated community donors can be effectively and safely used as an
      alternative to related family donors. Furthermore, several recent studies suggest
      that it may be possible to store granulocyte concentrates for 24 to 48 hours with
      adequate preservation of neutrophil function. This review summarizes the current
      role of granulocyte transfusion therapy in infectious diseases and highlights
      important recent advances.

PMID- 11303150
TI  - The use of granulocyte colony-stimulating factor for treatment of autoimmune
      neutropenia.
AB  - The advent of better diagnostic tools, molecular techniques, and cytokine
      therapies have come together at the end of the 20th century to provide an
      improved outlook for patients with autoimmune neutropenia. Severe chronic
      neutropenia is no longer idiopathic in most cases, and growth factor therapy can
      be safely offered to selected patient groups. Previously unsuccessful and even
      dangerous forms of treatment are no longer appropriate, and G-CSF treatment
      appears to be safe when administered long term. Fears about transformation of
      these disorders into acute myeloblastic leukemia probably relate to the
      underlying natural history of these disorders rather than to their treatment.

PMID- 11303151
TI  - Hematopoietic growth factors in the older cancer patient.
AB  - Aging is associated with a progressive decline in the functional reserve of
      multiple organ systems, which may lead to enhanced susceptibility to stress such
      as that caused by cancer chemotherapy. Myelodepression is the most common and the
      most commonly fatal complication of antineoplastic drug therapy and may represent
      a serious hindrance to the management of cancer in older individuals. This is
      already a common and pervasive problem and promises to become more so. Currently
      60% of all neoplasms occur in persons aged 65 years and older, and this
      percentage is expected to increase as the population ages. This well-known
      phenomenon, sometimes referred to as squaring or the age pyramid, is caused by
      the combination of an increasing life expectancy and a decreasing birth rate.
      This article explores the use of hematopoietic growth factors in the older cancer
      patient after reviewing the influence of age on hemopoiesis and chemotherapy
      related complications. The issue is examined in terms of effectiveness and cost.
      An outline of the assessment of the older cancer patient is provided at the end
      of the chapter as a frame of reference for clinical decisions.

PMID- 11303152
TI  - Patient volume per surgeon does not predict survival in adult level I trauma
      centers.
AB  - BACKGROUND: The 1999 American College of Surgeons resources for optimal care
      document added the requirement that Level I trauma centers admit over 240
      patients with Injury Severity Score (ISS) > 15 per year or that trauma surgeons
      care for at least 35 patients per year. The purpose of this study was to test the
      hypothesis that high volume of patients with ISS > 15 per individual trauma
      surgeon is associated with improved outcome. METHODS: Data were obtained from the
      trauma registry of the five American College of Surgeons-verified adult Level I
      trauma centers in our mature trauma system between January 1, 1998, and March 31,
      1999. Data abstracted included age, sex, Glasgow Coma Scale (GCS) score,
      intensive care unit length of stay, hospital length of stay, probability of
      survival (Ps), mechanism of injury, number of patients per each trauma surgeon
      and institution, and mortality. Multiple logistic regression was performed to
      select independent variables for modeling of survival. RESULTS: From the five
      Level I centers there were 11,932 trauma patients in this time interval; of
      these, 1,754 patients (14.7%) with ISS > 15 were identified and used for
      analysis. Patients with ISS > 15 varied from 173 to 625 per institution; trauma
      surgeons varied from 8 to 25 per institution; per-surgeon patient volume varied
      from 0.8 to 96 per year. Logistic regression analysis revealed that the best
      independent predictors of survival were Ps, GCS score, age, mechanism of injury,
      and institutional volume (p < 0.01). Age and institutional volume correlated
      negatively with survival. Analysis of per-surgeon patient caseload added no
      additional predictive value (p = 0.44). CONCLUSION: The significant independent
      predictors of survival in severely injured trauma patients are Ps, GCS score,
      age, mechanism of injury, and institutional volume. We found no statistically
      meaningful contribution to the prediction of survival on the basis of per-surgeon
      patient volume. Since this volume criterion for surgeon enpanelment and trauma
      center designation would not be expected to improve outcome, such a requirement
      should be justified by other measures or abandoned.

PMID- 11303153
TI  - A population-based study of geriatric trauma in a rural state.
AB  - BACKGROUND: Urban geriatric trauma patients are known to die more often than
      their younger counterparts. Little is known of the fate of geriatric trauma
      patients in a rural environment where delays to definitive treatment are
      frequent. We hypothesized that rural trauma patients would do worse than their
      urban counterparts because of prolonged delays to definitive care. METHODS: Five
      year retrospective analysis of all trauma deaths occurring within a rural state
      and retrospective outcome analysis of trauma patients admitted to a tertiary care
      facility who were less than 55 years old (defined as young) and 55 or more years
      old (defined as old). Outcome analysis was performed comparing old and young
      rural hospitalized patients to the Major Trauma Outcome Study data set collected
      in major urban trauma centers. RESULTS: Of the total trauma deaths in the state,
      32.5% were old. Old patients were less likely to die at the scene of the injury
      than were their younger counterparts (R2 = 0.84, p < 0.001). Hospitalized old
      patients had a significantly higher mean Revised Trauma Score and a significantly
      lower Injury Severity Score, a higher complication rate, and a higher mortality
      rate than did hospitalized young patients. The young group had a significantly
      better survival (W = 0.59, Z = -3.49, p = 0.0001) than the MTOS data set, but the
      old group had a significantly worse survival (W = -1.8, Z = -3.49, p = 0.001).
      CONCLUSION: In a rural environment, old trauma patients die more commonly in the
      hospital than their younger counterparts, who die more commonly at the scene. Old
      trauma patients who die in the hospital were less severely injured than their
      younger counterparts who died in the hospital. Old patients admitted to this
      rural trauma center have a significantly worse survival than their urban
      counterparts despite the fact that young rural trauma patients do significantly
      better than their urban counterparts. Understanding the demographics of rural
      geriatric trauma may be useful in allocating resources in rural trauma system
      design. It must be understood that despite relatively low injury severity and
      physiologic stability, there is a significant potential for rural geriatric
      trauma patients to do poorly.

PMID- 11303154
TI  - Impact of nosocomial infections in trauma: does age make a difference?
AB  - BACKGROUND: The effect of age and infection on outcome after trauma is unknown.
      We evaluated the incidence and impact that nosocomial infection (NI) and age have
      on morbidity and mortality. Several risk factors were identified and analyzed for
      correlation with infection. METHODS: Prospective data were collected on patients
      admitted for > or = 3 days over a 2-year period. Each patient was followed by an
      infectious disease specialist throughout their hospitalization. Centers for
      Disease Control and Prevention guidelines were used to diagnose infection.
      RESULTS: Of the 3,254 patients admitted, 88% were < 65 and 12% were > or = 65
      years of age. Injury Severity Score was not significantly different (older vs.
      younger). Five hundred one (17.4%) of the younger patients developed an NI with a
      significantly higher hospital length of stay (LOS), intensive care unit (ICU)
      LOS, and mortality compared with the noninfected group. One hundred forty-seven
      (39%) of the older group developed an NI and also had significant increases in
      hospital LOS, ICU LOS, and mortality. Older infected patients had the highest
      hospital LOS, ICU LOS, and mortality. The greatest relative risk of mortality was
      demonstrated with the combination of increased age and NI. Once infected,
      however, younger patients with penetrating trauma had a greater relative risk of
      mortality in the group-specific comparison. Many risk factors were associated
      with infection. Only chronic obstructive pulmonary disease in elderly trauma
      patients was a significant independent risk factor for infection. CONCLUSION: NI
      significantly increases hospital LOS, ICU LOS, and mortality after injury. Age
      increases risk of infection matched for injury severity, with a significantly
      higher hospital LOS, ICU LOS, and mortality. Once infected, however, younger
      patients with penetrating trauma have the greatest risk of mortality. Chronic
      obstructive pulmonary disease in elderly trauma patients was found to be an
      independent predictor of infection.

PMID- 11303155
TI  - Start with a subjective assessment of skin temperature to identify hypoperfusion
      in intensive care unit patients.
AB  - OBJECTIVE: To determine whether physical examination alone or in combination with
      biochemical markers can accurately diagnose hypoperfusion. METHODS: Data from 264
      consecutive surgical intensive care unit patients were collected by two
      intensivists and included extremity temperature, vital signs, arterial lactate,
      arterial blood gases, hemoglobin, and pulmonary artery catheter values with
      derived indices. Days of data were divided into data collected from patients with
      cool extremities (cool skin temperature [CST] group) versus warm extremities
      (warm skin temperature [WST] group). Values are means +/- SD. Comparisons between
      groups were made by two-tailed unpaired t test; significance was assumed for p <
      or = 0.05. RESULTS: There were 328 days of observations in the CST group versus
      439 in the WST group. There were no differences (p > 0.05) between CST and WST
      data with regard to heart rate (107 +/- 14 vs. 99 +/- 19 beats/min), systolic
      blood pressure (118 +/- 24 vs. 127 +/- 28 mm Hg), diastolic blood pressure (57 +/
      14 vs. 62 +/- 15 mm Hg), pulmonary artery occlusion pressure (14 +/- 6 vs. 16 +/
      5 mm Hg), Fio2 (0.48 +/- 0.7 vs. 0.45 +/- 0.2), hemoglobin (8.8 +/- 1.6 vs. 9.3
      +/- 1.3 g/dL), Pco2 (44.3 +/- 11.8 vs. 40.7 +/- 9.2 mm Hg), or Po2 (96.4 +/- 12.6
      vs. 103.8 +/- 22.2 mm Hg). However, cardiac output (5.3 +/- 2.2 vs. 8.2 +/- 2.6
      L/min), cardiac index (2.9 +/- 1.2 vs. 4.3 +/- 1.2 L/min/m2), pH (7.32 +/- 0.2
      vs. 7.39 +/- 0.07), TCO2 (19.5 +/- 3.1 vs. 25.1 +/- 4.8 mEq/L), and Svo2 (60.2 +/
      4.4% vs. 68.2 +/- 7.8%) were all significantly lower (p < 0.05) in CST patients
      compared with WST patients. By comparison, lactate (4.7 +/- 1.5 vs. 2.2 +/- 1.6
      mmol/L, p < 0.05) was significantly elevated in patients with cool extremities.
      CONCLUSION: Combining physical examination with serum bicarbonate and arterial
      lactate identifies patients with hypoperfusion as defined by low Svo2 and cardiac
      index. Hypoperfusion may occur despite supranormal cardiac indices. Patients with
      cool extremities and elevated lactate levels may benefit from a pulmonary artery
      catheter to guide but not initiate therapy.

PMID- 11303156
TI  - Splanchnic perfusion evaluation during hemorrhage and resuscitation with gastric
      near-infrared spectroscopy.
AB  - OBJECTIVE: The purpose of this study was to use a prototype side-illuminating
      near-infrared spectroscopy (NIRS) nasogastric probe to continuously measure
      changes in gastric tissue oxygen saturation (Sto2) in a pig hemorrhage model.
      METHODS: Swine (n = 12; 6 per group) underwent laparotomy and placement of a
      gastric NIRS probe, jejunal tonometer, superior mesenteric artery (SMA) flow
      probe, and a portal vein catheter. Animals underwent hemorrhage (28 mL/kg) t = 0
      to 20 minutes (where t = time). Pigs in group I were resuscitated (t = 20-40
      minutes) with lactated Ringer's solution (84 mL/kg), whereas group II had no
      resuscitation. RESULTS: A significant decrease in mean arterial pressure and SMA
      flow was observed after hemorrhage. SMA flow significantly correlated in group I
      with both NIRS Sto2 (r = 0.58, p = 0.0001) and regional CO2 (r = -0.54, p =
      0.0001). In group II, superior mesenteric flow correlated with NIRS Sto2 (r =
      0.30, p = 0.03), but not regional CO2 (r = -0.23, p = 0.09). CONCLUSION: Direct
      measurement of tissue oxygen saturation with a prototype side-illuminating near
      infrared spectroscopy gastric probe appeared to rapidly reflect changes in
      splanchnic perfusion.

PMID- 11303157
TI  - Surgeon-performed ultrasound in the critical care setting: its use as an
      extension of the physical examination to detect pleural effusion.
AB  - BACKGROUND: Critically ill surgical patients are often difficult to assess for
      complications because of their altered sensorium, multiple monitoring devices,
      and immobility. Surgeon-performed ultrasound may enhance the physical examination
      of these patients and provide for an early detection of select complications. We
      hypothesized that a focused thoracic ultrasound examination could reliably detect
      a pleural effusion and the results could be used in the decision matrix for
      patient care. METHODS: Serial focused thoracic ultrasound examinations were
      performed by a surgeon and a medical student on critically ill patients. The
      medical student learned select facets of the physical examination and then
      demonstrated how ultrasound imaging could enhance these findings. Ultrasound
      images were recorded on hard copy and videotape, with the results available to
      the surgical intensive care unit and surgery teams. The images were reviewed and
      compared with the chest radiograph readings. RESULTS: Forty-seven patients
      underwent 140 ultrasound examinations. There were 85 true-negative, 46 true
      positive, 9 false-negative, and zero false-positive examination results, yielding
      an 83.6% sensitivity, 100% specificity, and 94% accuracy. Of the 46 true-positive
      results, thoracentesis was performed or a thoracostomy tube was placed in 5
      patients. Nine false-negative ultrasound examinations occurred in six patients,
      five of whom had their effusions detected on computed tomographic scans.
      CONCLUSION: A focused thoracic ultrasound examination reliably detects pleural
      effusions in critically ill patients, and the results can be used successfully in
      the decision matrix for patient care.

PMID- 11303158
TI  - Trauma case management and clinical pathways: prospective evaluation of their
      effect on selected patient outcomes in five key trauma conditions.
AB  - BACKGROUND: This study evaluated the implementation of clinical pathways and case
      management between July 1998 and July 1999 in five key trauma conditions: severe
      head injury, fractured ribs, fractured pelvis, blunt abdominal trauma, and
      fractured femurs presenting to a single trauma service. METHODS: Thirteen key
      elements of care with expected outcomes were defined for each key trauma
      condition. Deviations from expected outcome were defined as variances. Attainment
      of the expected outcomes was measured before (stage 1) and after introduction
      (stages 2 and 3) of clinical pathways and case management. Nonattained outcomes
      were quantified and categorized into time of occurrence, and relationship to
      staff, patient, or system. RESULTS: Two hundred thirty-five patients were
      studied, with a mean age of 41.8 (SD, 20.6) years and mean Injury Severity Score
      (ISS) of 11.7 (SD, 11.0). The mean number of observed variances per patient for
      stage 1 was 51.7 (SD, 43.5); stage 2, 42.3 (SD, 32.9); and stage 3, 23.2 (SD,
      21.7) (p = 0.0001 for both stage 1 and stage 2 compared with stage 3). There was
      a significant improvement in outcomes achieved from stage 1 (92.7%; 95%
      confidence interval, 92.5-92.9%), to stage 3 (96.7%; 95% confidence interval,
      96.5-96.9%). Of the total number of variances seen, 0.2% related to system
      errors, 25% related to patient factors, and 75.8% related to staff. The
      proportion of staff-related variances was significantly reduced in stage 3.
      CONCLUSION: Clinical pathways and case management identified areas in need of
      remedial action and improved the delivery of patient care to our trauma
      population. It has set a template for the future management of our trauma
      service.

PMID- 11303159
TI  - Hemoperitoneum score helps determine need for therapeutic laparotomy.
AB  - PURPOSE: Sonography provides a fast, portable, and noninvasive method for patient
      assessment. However, the benefit of providing real-time ultrasound (US) imaging
      and fluid quantification shortly after patient arrival has not been explored. The
      objective of this study was to prospectively validate a US hemoperitoneum scoring
      system developed at our institution and determine whether sonography can predict
      a therapeutic operation. METHODS: For 12 months, prospective data on all patients
      undergoing a trauma sonogram were recorded. All sonograms positive for free fluid
      were given a hemoperitoneum score. The US score was compared with initial
      systolic blood pressure and base deficit to assess the ability of sonography to
      predict a therapeutic laparotomy. RESULTS: Forty of 46 patients (87%) with a US
      score > or = 3 required a therapeutic laparotomy. Forty-six of 54 patients with a
      US score < 3 (85%) did not need operative intervention. The sensitivity of
      sonography was 83% compared with 28% and 49% for systolic blood pressure and base
      deficit, respectively, in determining the need for therapeutic operation.
      CONCLUSION: We conclude that the majority of patients with a score > or = 3 will
      need surgery. The US hemoperitoneum scoring system was a better predictor of a
      therapeutic laparotomy than initial blood pressure and/or base deficit.

PMID- 11303160
TI  - The impact on outcomes in a community hospital setting of using the AANS
      traumatic brain injury guidelines. Americans Associations for Neurologic
      Surgeons.
AB  - BACKGROUND: Traumatic brain injury poses a serious public health challenge.
      Treatment paradigms have dramatically shifted with the introduction of the
      American Association of Neurologic Surgeons (AANS) Guidelines for the Management
      of Severe Head Injury. Implementation of the AANS guidelines positively affects
      patient outcomes and can be successfully introduced in a community hospital
      setting. METHODS: Data were collected both retrospectively and prospectively from
      the records of all trauma patients between 1994 and 1999. A cohort of 93 patients
      was selected. Thirty-seven patients were treated before the implementation of the
      AANS guidelines, and these were statistically compared with 56 patients treated
      after the implementation of the guidelines. RESULTS: Implementation of the
      recommendations in the AANS guidelines in a standardized protocol resulted in a
      9.13 times higher odds ratio of a good outcome relative to the odds of a poor
      outcome or death compared with a group managed before the practice change. A
      Glasgow Coma Scale (GCS) admission score > 8 was associated with a 6.58 times
      higher odds ratio of a good outcome compared with a GCS admission score < or = 8.
      Odds ratio of a good outcome decreased by a factor of 0.92 for each year increase
      in age of patients starting at age 9. A dedicated neurotrauma team and
      comprehensive treatment algorithms are critical elements to this success.
      Hospital charges increased by more than $97,000 per patient, but are justifiable
      in the face of significantly improved outcomes. CONCLUSION: Implementation of a
      traumatic brain injury protocol in a community hospital setting is practical and
      efficacious. Appropriate invasive monitoring of systemic and cerebral parameters
      guides care decisions. The protocol results in an increase in resource usage, but
      it also results in statistically improved outcomes justifying the increase in
      expenditures.

PMID- 11303161
TI  - Determining optimal cardiac preload during resuscitation using measurements of
      ventricular compliance.
AB  - BACKGROUND: While the right ventricular end-diastolic volume index (RVEDVI) has
      been shown to be a better indicator of preload than cardiac filling pressures,
      optimal values during resuscitation from trauma are unknown. This study examines
      right ventricular stiffness as a guide to optimal values of RVEDVI. METHODS:
      Prospective study of 19 critically injured patients monitored with a volumetric
      pulmonary artery catheter during resuscitation. Per resuscitation protocol, the
      target RVEDVI was > or = 120 mL/m2. Sequential fluid boluses of 500 to 1000 mL
      were administered to obtain at least four values of RVEDVI and right ventricular
      end-diastolic pressure (estimated by central venous pressure [CVP]). For each
      patient, nonlinear regression was used to construct the ventricular compliance
      curve based on the equation, CVP = aek(RVEDVI), where k is the coefficient of
      chamber stiffness. RESULTS: Overall, the derived compliance curves had excellent
      fit with the theoretical equation (mean R2, 0.95 +/- 0.04). Mean k was 0.043 +/-
      0.012 (range, 0.029-0.067). For each patient, mean RVEDVI during resuscitation
      was significantly correlated with k (R2 = 0.75, p < 10-5) indicating that chamber
      stiffness, measured during initial fluid administration, may be used to determine
      RVEDVI during the ensuing resuscitation. CONCLUSION: In critically injured
      patients, bedside assessment of right ventricular compliance is possible and may
      help determine optimal values of RVEDVI during resuscitation.

PMID- 11303162
TI  - Prehospital resuscitative thoracotomy for cardiac arrest after penetrating
      trauma: rationale and case series.
AB  - OBJECTIVE: The purpose of this study is to present the rationale for an algorithm
      that describes the place of resuscitative thoracotomy in the prehospital
      management of a patient with penetrating chest injury, and to review a 6-year
      experience using this algorithm. METHODS: This study was a retrospective review
      of all cases where a prehospital thoracotomy was performed by the medical teams
      of the London Helicopter Emergency Medical Service. RESULTS: Thirty-nine
      prehospital thoracotomies were performed. Four (10%) patients survived, one with
      long-term disability. Factors associated with survival were stab wound, single
      cardiac wound, cardiac tamponade, and loss of pulse in the presence of an
      experienced prehospital doctor. CONCLUSION: Current evidence suggests that
      patients who suffer a cardiac arrest more than 10 minutes away from emergency
      room thoracotomy are very unlikely to survive. Prehospital thoracotomy is
      associated with a small number of survivors. This intervention should be
      considered if there is an appropriately experienced, trained, and equipped doctor
      present, who is acting within a trauma system with ongoing training and quality
      assurance.

PMID- 11303163
TI  - Chest tube removal: end-inspiration or end-expiration?
AB  - BACKGROUND: Recurrent pneumothorax is the most significant complication after
      discontinuation of thoracostomy tubes. The primary objective of the present study
      was to determine which method of tube removal, at the end of inspiration or at
      the end of expiration, is associated with a lesser risk of developing a recurrent
      pneumothorax. A secondary objective was to identify potential risk factors for
      developing recurrence. METHODS: A prospective study of 102 chest tubes in 69
      trauma patients (1.5 tubes per patient) randomly assigned to removal at the end
      of inspiration (n = 52) or the end of expiration (n = 50). RESULTS: Recurrent
      pneumothorax or enlargement of a small but stable pneumothorax was observed after
      the removal of four chest tubes in the end-inspiration group (8%) and after
      discontinuation of three chest tubes (6%) in the end-expiration group (p = 1.0).
      Of those, only two tubes in the end-inspiration group and 1 tube in the end
      expiration group required repeat closed thoracostomy. Multiple factors were
      analyzed that did not adversely affect outcome. These included patient age,
      Injury Severity Score, Revised Trauma Score, mechanism of injury, hemothorax,
      thoracotomy, thoracostomy, previous lung disease, chest tube duration, the
      presence of more than one thoracostomy tube in the same hemithorax, or a small
      (but stable) pneumothorax at the time of tube removal. CONCLUSIONS:
      Discontinuation of chest tubes at the end of inspiration or at the end of
      expiration has a similar rate of post-removal pneumothorax. Both methods are
      equally safe.

PMID- 11303164
TI  - Major trauma in elderly adults receiving lipid-lowering medications.
AB  - BACKGROUND: Some clinical trials, laboratory experiments, and in vitro studies
      suggest that lipid-lowering medications predispose a person to traumatic injury.
      METHODS: We used population-based administrative database analysis to study
      adults age 65 years or more over a 5-year interval (n = 1,348,259). RESULTS:
      About 12% of the cohort received a prescription for a lipid-lowering medication
      and about 88% did not. The two groups had similar distributions of age, gender,
      and income. Overall, 2,557 (0.2%) were hospitalized for major trauma. Those who
      received a lipid-lowering medication were 39% less likely to sustain a major
      trauma than those who did not receive such medication (95% confidence interval,
      29 to 47). Similar results were observed after adjustment for age, gender, and
      income; cardiac and neurologic medications; and lethality. No other cardiac or
      neurologic medication was associated with an apparent safety advantage.
      CONCLUSION: Lipid-lowering medications do not lead to a clinically important
      increase in the absolute risk of major trauma for elderly patients in the
      community.

PMID- 11303165
TI  - Assessing the true risk of abdominal solid organ injury in hospitalized rib
      fracture patients.
AB  - BACKGROUND: Despite the lack of evidence, traditional trauma teaching has
      suggested that low rib fractures increase the risk of abdominal solid organ
      injury (ASOI). This study was designed to assess if in fact this is true, and to
      try and define other factors that increased the risk of ASOI in rib fracture
      patients. METHODS: The charts of 476 hospitalized rib fracture trauma patients
      were reviewed. Data were collected for age; sex; Injury Severity Score (ISS); rib
      fracture location; and the presence or absence of injuries to the abdominal
      organs, head, neck, face, thorax, great vessel, heart, thoracolumbar spine,
      pelvis, and extremities. RESULTS: The probability of liver injury increased with
      the presence of any right-sided rib fracture, any low rib fracture, female
      gender, young age, and an elevated ISS. The probability of splenic injury
      increased with the presence of left-sided rib fractures only, any low rib
      fracture, young age, and an elevated ISS. CONCLUSION: In hospitalized trauma
      patients, low rib fractures, right-sided rib fractures, female gender, young age,
      and an elevated ISS increased the probability of liver injury; and low rib
      fractures, left-sided only rib fractures, young age, and an elevated ISS
      increased the probability of splenic injury. Associated pelvic fractures and long
      bone fractures did not increase the likelihood of ASOI in this cohort.

PMID- 11303166
TI  - Abdominal ultrasound examination in pregnant blunt trauma patients.
AB  - BACKGROUND: The ability of abdominal ultrasound to detect intraperitoneal fluid
      in the pregnant trauma patient has been questioned. METHODS: Pregnant blunt
      trauma patients admitted to a Level I trauma center during an 8-year period were
      reviewed. Ultrasound examinations were used to detect intraperitoneal fluid and
      considered positive if such fluid was identified. RESULTS: One hundred twenty
      seven (61%) of 208 pregnant patients had abdominal ultrasound during initial
      evaluation in the emergency department. Seven patients had intra-abdominal
      injuries, and six had documented hemoperitoneum. Ultrasound identified
      intraperitoneal fluid in five of these six patients (sensitivity, 83%; 95%
      confidence interval, 36-100%). In the 120 patients without intra-abdominal
      injury, ultrasound was negative in 117 (specificity, 98%; 95% confidence
      interval, 93-100%). The three patients without intra-abdominal injury but with a
      positive ultrasound had the following: serous intraperitoneal fluid and no
      injuries at laparotomy (one) and uneventful clinical courses of observation
      (two). CONCLUSION: The sensitivity and specificity of abdominal ultrasonography
      in pregnant trauma patients is similar to that seen in nonpregnant patients.
      Occasional false negatives occur and a negative initial examination should not be
      used as conclusive evidence that intra-abdominal injury is not present.
      Ultrasound has the advantages of no radiation exposure.

PMID- 11303167
TI  - Ultrastructural and functional characteristics of blast injury-induced
      neurotrauma.
AB  - OBJECTIVE: The present study investigates whether whole-body or local (chest)
      exposure to blast overpressure can induce ultrastructural, biochemical, and
      cognitive impairments in the brain. METHODS: Male Wistar rats were trained for an
      active avoidance task for 6 days. On day 6, rats that had acquired the avoidance
      response were subjected to whole-body blast injury (WBBI), generated by large
      scale shock tube (n = 40); or local (chest) blast injury (LBI), induced by blast
      overpressure focused on the right middle thoracic region and generated by small
      scale shock tube (n = 40) while the heads of animals were protected. At the
      completion of cognitive testing, rats were killed at 3 hours, 24 hours, and 5
      days after injury. Ultrastructural changes in the hippocampus were analyzed
      electron microscopically. Parameters of oxidative stress (malondialdehyde and
      superoxide anion generation) and antioxidant enzyme defense (superoxide dismutase
      and glutathione peroxidase activity) were measured in the hippocampus to assess
      biochemical changes in the brain after blast. RESULTS: Ultrastructural findings
      in animals subjected to WBBI or LBI demonstrated swellings of neurons, glial
      reaction, and myelin debris in the hippocampus. All rats revealed significant
      deficits in performance of the active avoidance task 3 hours after injury, but
      deficits persisted up to day 5 after injury only in rats subjected to WBBI.
      Oxidative stress development and altered antioxidant enzyme defense was observed
      in animals in both groups. Cognitive impairment and biochemical changes in the
      hippocampus were significantly correlated with blast injury severity in both WBBI
      and LBI groups. CONCLUSION: These results confirm that exposure to blast
      overpressure induces ultrastructural and biochemical impairments in the brain
      hippocampus, with associated development of cognitive deficits.

PMID- 11303168
TI  - Stab wounds to the gluteal region: a management strategy.
AB  - OBJECTIVE: To examine the utility of a protocol for treating stab wounds to the
      gluteal region. These are uncommon and potentially lethal, and the location of
      injury influences the rate and severity of associated injuries. This was a
      retrospective, uncontrolled study. METHODS: Patients who sustained gluteal stab
      wounds and were treated according to our predetermined protocol that classifies
      injuries as upper or lower zone were reviewed, and associated injuries and
      outcome were measured. RESULTS: Of 27 gluteal stab wounds in 17 patients, 53%
      were classified as upper zone and 47% as lower zone injuries. Sixty-six percent
      of the upper zone injuries had associated neurologic, vascular, or visceral
      injuries that required invasive procedures or surgery, compared with 12.5% for
      lower zone injuries (p < 0.05). CONCLUSION: Upper zone gluteal stab wounds
      require prompt multisystem evaluation with mandatory angiography and aggressive
      management. Lower zone wounds need observation and repeated evaluations.

PMID- 11303169
TI  - Early weight-bearing after statically locked reamed intramedullary nailing of
      comminuted femoral fractures: is it a safe procedure?
AB  - BACKGROUND: The purpose of this study was to determine the safety of early weight
      bearing after statically locked reamed nailing of comminuted fractures of the
      femoral diaphysis, and to assess the rate of implant failure and fracture
      healing. METHODS: Thirty consecutive patients with comminuted diaphyseal femur
      fractures (Winquist type II, III, and IV) were treated with statically locked
      reamed intramedullary nailing. Six patients were lost to follow-up, and the
      remaining 24 patients were followed at least 1 year. Early weight-bearing was
      allowed and encouraged in the first 2 weeks after the operation. The nail
      diameters were 13 mm in 16 patients, 12 mm in 6 patients, and 14 mm in 2
      patients. RESULTS: Most of the patients could start weight-bearing between the
      first 2 and 4 weeks postoperatively. None of the patients, except one, were using
      any walking aids at the second month postoperatively. All the fractures healed
      without any significant complications. Nail bending or breakage did not occur in
      any patients, but there was slight bending in one distal interlocking screw and
      one proximal interlocking screw. The fractures of the patients with bent screws
      healed uneventfully. CONCLUSION: This study showed that early weight-bearing
      after reamed static interlocking nailing of Winquist type II, III, and IV femoral
      fractures is a safe and effective method, and the risk of implant failure does
      not preclude the procedure.

PMID- 11303170
TI  - Functional outcome of high-pressure injection injuries of the hand.
AB  - BACKGROUND: High-pressure injection (HPI) injury of the hand is a serious injury
      that can be potentially devastating. There have been a number of publications on
      the results of its treatment, but we are not aware of a report on the functional
      outcome of these hands. METHODS: We assessed the functional outcome of 15
      patients with HPI injuries. All patients were treated operatively, with a mean
      delay of 11.7 hours. The patients were examined by a doctor and an occupational
      therapist using a work simulator. RESULTS: Our study revealed a significant
      reduction of static and dynamic muscle testing parameters compared with the
      uninjured hand. Six patients lost a digit and four patients had to change their
      occupation after the injury. CONCLUSION: Deterioration of hand function is a
      predictable outcome of HPI injury. This information should be shared with the
      patient at the outset so as to avoid subsequent disappointment.

PMID- 11303171
TI  - Intravenous rFVIIa administered for hemorrhage control in hypothermic
      coagulopathic swine with grade V liver injuries.
AB  - BACKGROUND: Intravenous administration of recombinant activated human clotting
      factor VII (rFVIIa) has been used successfully to prevent bleeding in hemophilia
      patients undergoing elective surgery, but not in previously normal trauma
      patients. This study was conducted to determine whether rFVIIa was a useful
      adjunct to gauze packing for decreasing blood loss from grade V liver injuries in
      hypothermic and coagulopathic swine. METHODS: All animals (n = 10, 35 +/- 2 kg)
      underwent a 60% isovolemic exchange transfusion with 6% hydroxyethyl starch and
      were cooled to 33 degrees C core temperature. The swine then received a grade V
      liver injury and 30 seconds later, either 180 microg/kg rFVIIa, or saline
      control. All animals were gauze packed 30 seconds after injury and resuscitated
      5.5 minutes after injury with lactated Ringer's solution to their preinjury mean
      arterial pressure. Posttreatment blood loss, mean arterial pressure,
      resuscitation volume, and clotting studies were monitored for 1 hour. Histology
      of lung, kidney, and small bowel were obtained to evaluate for the presence of
      microvascular thrombi. RESULTS: At the time of injury, core temperature was 33.3
      degrees +/- 0.4 degrees C, hemoglobin was 6 +/- 0.7 g/dL, prothrombin time was
      19.1 +/- 1.0 seconds, activated partial thromboplastin time was 29.0 +/- 4.8
      seconds, fibrinogen was 91 +/- 20 mg/dL, and platelets were 221 +/- 57 x 105/mL,
      with no differences between groups (p > 0.05). Clotting factor levels confirmed a
      coagulopathy at the preinjury point. The posttreatment blood loss was less (p <
      0.05) in group 1 (527 +/- 323 mL), than in group 2 (976 +/- 573 mL). The
      resuscitation volume was not different (p > 0.05). One-hour survival in both
      groups was 100%. Compared with the control group, rFVIIa increased the
      circulating levels of VIIa and, despite hypothermia, shortened the prothrombin
      time 5 minutes after injection (p < 0.05). Laboratory evaluation revealed no
      systemic activation of the clotting cascade. Postmortem evaluation revealed no
      evidence of large clots in the hepatic veins or inferior vena cava, or
      microscopic thrombi in lung, kidney, or small intestine. CONCLUSION: rFVIIa
      reduced blood loss and restored abnormal coagulation function when used in
      conjunction with liver packing in hypothermic and coagulopathic swine. No adverse
      effects were identified.

PMID- 11303172
TI  - Multiple spine fractures in an adolescent snowboarder: case report.

PMID- 11303173
TI  - Cord transection by guillotine effect of fractured ribs.

PMID- 11303174
TI  - Traumatic proper hepatic artery occlusion: case report.

PMID- 11303175
TI  - Celiac axis ligation after gunshot wound to the abdomen: case report and
      literature review.

PMID- 11303176
TI  - Femoral arterial graft failure caused by the secondary abdominal compartment
      syndrome.

PMID- 11303177
TI  - "Incidental" pericardial effusion during surgeon-performed ultrasonography in
      patients with blunt torso trauma.

PMID- 11303178
TI  - Blunt traumatic rupture of the heart in a child: case report and review of the
      literature.

PMID- 11303179
TI  - Sonographic diagnosis of a pneumothorax inapparent on plain radiography:
      confirmation by computed tomography.

PMID- 11303180
TI  - Obstructing endobronchial inflammatory polyps: treatment with urgent laser
      photoablation.

PMID- 11303181
TI  - Penetrating trauma causing partial disruption of a duplicated ureter: case
      report.

PMID- 11303182
TI  - Minor head injury: 13 is an unlucky number.

PMID- 11303183
TI  - Massive subcutaneous emphysema after blunt tracheal rupture.

PMID- 11303184
TI  - The changing tides in obstetrics and gynecology.

PMID- 11303185
TI  - Molecular tools to reestablish progestin control of endometrial cancer cell
      proliferation.
AB  - OBJECTIVE: Endometrial cancers often arise in a setting of estrogen stimulation
      unopposed by the differentiating effects of progesterone. Our laboratory and
      others have previously shown that progesterone receptor down-regulation or
      perturbation of progesterone receptor isoform A or B expression is associated
      with the development of poorly differentiated endometrial cancers that are not
      growth inhibited by progestins. The purpose of these studies was to reestablish
      high progesterone receptor isoform A and B gene expressions in such endometrial
      cancer cells and to examine the effects of progestin treatment on cell growth and
      metastatic potential after this transformation. STUDY DESIGN: To induce high
      levels of expression of the progesterone receptor isoforms in KLE and Hec50
      endometrial cancer cells, adenoviral vectors encoding the genes for progesterone
      receptor isoforms A and B were created. The characteristic ability of cancer
      cells to grow independently of anchorage to the surrounding solid matrix was
      measured by counting colony formation on soft agar for 8 to 14 days. Cell
      proliferation in response to a time course of progestin treatment was tested with
      flow cytometry. RESULTS: After treatment with a control vector without a
      progesterone receptor--encoding insert, no effect of progestin treatment on cell
      proliferation was found; after treatment with vectors encoding progesterone
      receptor isoform A or B, however, progestin treatment resulted in significant
      inhibition of cell growth. The anchorage-independent cell growth on soft agar
      assay showed that by 8 to 14 days the number of cell colonies was reduced by 50%
      relative to control preparations in the presence of progesterone receptor isoform
      A plus progestin (P <.0001, both Hec50 and KLE cell lines) and by 90% in the
      presence of progesterone receptor isoform B plus progestin (P <.0001, both Hec50
      and KLE cell lines). Progestin treatment also resulted in a time-dependent
      reduction in cell proliferation as measured by flow cytometry. Although
      transfection with both progesterone receptor isoforms A and B reduced cell
      proliferation according to our assays, progesterone receptor isoform B caused a
      much more dramatic decrease in cell growth (P =.001, Hec50 cells; P <.0001, KLE
      cells). CONCLUSION: In poorly differentiated endometrial cancer cells that are
      resistant to progestin therapy, adenovirus-induced expressions of progesterone
      receptors A and B reestablish progestin control of endometrial cancer cell
      proliferation.

PMID- 11303186
TI  - Regulation of plasminogen activator inhibitor 1 expression by interaction of
      epidermal growth factor with progestin during decidualization of human
      endometrial stromal cells.
AB  - OBJECTIVE: During human pregnancy implantation, trophoblasts invade maternal
      blood vessels in a process that risks hemorrhage. Previous studies have
      demonstrated enhanced expression of type 1 plasminogen activator inhibitor, the
      primary inhibitor of fibrinolysis, during progestin-induced decidualization of
      estradiol-primed human endometrial stromal cells in vivo and in vitro. Decidual
      cell-expressed plasminogen activator inhibitor 1 is appropriately positioned to
      avert implantational hemorrhage. Because of the absence of estrogen or
      progesterone response elements from the plasminogen activator inhibitor 1 gene
      promoter, I posited that epidermal growth factor mediates these steroid effects
      and that expression of epidermal growth factor receptor in human endometrial
      stromal cells is under ovarian steroid control. STUDY DESIGN: Confluent human
      endometrial stromal cells were exposed to vehicle control or to either estradiol
      (10(-8) mol/L) or medroxyprogesterone acetate (10(-7) mol/L), or both, with or
      without growth factors. After 40 hours the cultures were analyzed for plasminogen
      activator inhibitor 1 protein and messenger ribonucleic acid expressions.
      Immunostaining for epidermal growth factor receptor was carried out in sections
      of cycling and gestational endometrial tissues. RESULTS: In the absence of
      steroids, epidermal growth factor did not alter plasminogen activator inhibitor 1
      expression. In the absence of epidermal growth factor, estradiol and
      medroxyprogesterone acetate enhanced human endometrial stromal cell-secreted
      plasminogen activator inhibitor 1 protein levels 8-fold (n = 12; P <.001),
      whereas estradiol alone had no effect. Marked synergistic increases in
      plasminogen activator inhibitor 1 levels were elicited when epidermal growth
      factor was added with estradiol and medroxyprogesterone acetate (n = 12; 65-fold;
      P <.0001). Both transforming growth factor alpha and epidermal growth factor,
      which act through epidermal growth factor receptor, increased steady-state
      plasminogen activator inhibitor 1 messenger ribonucleic acid levels several-fold
      when added with estradiol and medroxyprogesterone acetate. In contrast,
      transforming growth factor beta, which does not activate epidermal growth factor
      receptor, did not elevate plasminogen activator inhibitor 1 messenger ribonucleic
      acid or protein levels whether added alone or with estradiol and
      medroxyprogesterone acetate. In correspondence with these in vitro observations,
      immunostaining for epidermal growth factor receptor was increased in human
      endometrial stromal cells undergoing decidualization in sections of secretory
      phase and first-trimester endometrial tissue. CONCLUSIONS: Taken together, these
      in vitro and in vivo results indicate that both epidermal growth factor and
      progesterone receptors are required for maximal plasminogen activator inhibitor 1
      expression by human endometrial stromal cells.

PMID- 11303187
TI  - Association of the C677T methylenetetrahydrofolate reductase mutation and
      elevated homocysteine levels with congenital cardiac malformations.
AB  - OBJECTIVE: The aim of this study was determine whether the cytosine-to-thymine
      mutation at base 677 of the gene for methylenetetrahydrofolate reductase (C677T
      MTHFR ), which has been associated with neural tube defects, is also associated
      with congenital cardiac malformations. STUDY DESIGN: Amniotic fluid homocysteine
      levels were measured and the presence or absence of the C677T MTHFR mutation in
      amniocytes was determined in stored amniotic fluid obtained from 26 pregnancies
      complicated by isolated (presumed multifactorial) fetal cardiac defects and from
      116 normal pregnancies. RESULTS: The pregnancies affected by fetal cardiac
      defects had higher amniotic fluid homocysteine levels (1.7 +/- 1.7 vs 1.0 +/- 0.7
      micromol/L; P =.07) and included more samples with homocysteine levels >90th
      percentile (27% vs 9%; P =.02) and more cases with the C677T MTHFR mutation (35%
      vs 13%; P =.01). Fifty percent of cases had either a high homocysteine level or
      the C677T MTHFR mutation (50% vs 20%; P =.003) and 12% had both (12% vs 0%; P
      =.0006). CONCLUSION: Fifty percent of these isolated congenital cardiac defects
      were associated with either the C677T MTHFR mutation or elevated amniotic fluid
      homocysteine levels, or both. This finding adds to what is already known about
      the multiple and complex biochemical and developmental functions of the
      homocysteine pathway.

PMID- 11303188
TI  - The lack of influence of age on male fertility.
AB  - OBJECTIVE: This study was undertaken to determine the effect of male aging on
      sperm quality as determined by semen analysis, the fertilization rate of human
      oocytes in vitro, and live birth rates. STUDY DESIGN: Retrospective analysis
      correlating outcome measures with male age was performed for 558 oocyte donation
      cycles in 441 couples. The oocyte donation model was chosen because it controls
      for oocyte quality and endometrial receptivity, which allows variations in sperm
      quality as a function of male age to be the only dependent variable. Outcome
      measures analyzed were semen analysis, fertilization rates in vitro, pregnancy
      rates, live birth rates, and cumulative live birth rates by life-table analysis.
      RESULTS: There was a negative correlation between male age and total sperm count,
      but there was no correlation between male age and any of the other parameters in
      the semen analysis. There was no association between male age and the
      fertilization rate of donated oocytes in vitro, pregnancy rates, or live birth
      rates. Recipient couples were grouped by quartiles of male age, and cumulative
      live birth rates were the same in the 4 groups. CONCLUSION: Whereas male aging is
      associated with a significant decline in total sperm count, this change is not
      reflected in a decreased fertilization rate or a decreased live birth rate in the
      oocyte donation model.

PMID- 11303189
TI  - Antiphospholipid antibodies in women at risk for preeclampsia.
AB  - OBJECTIVE: The aim of this study was to determine whether positive results of
      tests for any of 5 antiphospholipid antibodies are associated with recurrent
      preeclampsia among women with a history of preeclampsia in a previous pregnancy.
      STUDY DESIGN: Second-trimester serum samples were obtained from 317 women with
      preeclampsia in a previous pregnancy who were being followed up in a prospective
      treatment trial. The serum samples were measured by enzyme-linked immunoassay for
      immunoglobulin G and immunoglobulin M antibodies against 5 phospholipids.
      Positive results were analyzed with regard to preeclampsia, severe preeclampsia,
      intrauterine growth restriction, and preterm delivery. RESULTS: Sixty-two of the
      317 women (20%) had recurrent preeclampsia develop, 19 (6%) had severe
      preeclampsia, and 18 (5.8%) were delivered of infants with growth restriction.
      Positive results of tests for immunoglobulin G or immunoglobulin M
      antiphospholipid antibodies were not associated with recurrent preeclampsia.
      Positive results for immunoglobulin G or immunoglobulin M antibodies at the 99th
      percentile were also not associated with preterm delivery. Positive results at
      the 99th percentile for immunoglobulin G antiphosphatidylserine antibody were
      associated with severe preeclampsia, and positive results at the 99th percentile
      for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and
      antiphosphatidylglycerol antibodies were associated with intrauterine growth
      restriction. The positive predictive values for these outcomes all were
      approximately 30%. CONCLUSION: Positive results of testing for antiphospholipid
      antibodies in the second trimester were not associated with recurrent
      preeclampsia among women at risk because of a history of preeclampsia. Positive
      results for immunoglobulin G antiphosphatidylserine antibody were associated with
      severe preeclampsia, and positive results for immunoglobulin G anticardiolipin,
      antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated
      with intrauterine growth restriction. However, the positive predictive values for
      all these associations were modest. Testing for antiphospholipid antibodies
      during pregnancy is of little prognostic value in the assessment of the risk for
      recurrent preeclampsia among women with a history of preeclampsia.

PMID- 11303190
TI  - Characterization of the biologic activities of a recombinant human zona pellucida
      protein 3 expressed in human ovarian teratocarcinoma (PA-1) cells.
AB  - OBJECTIVE: This study was undertaken to clone and express a recombinant human
      zona pellucida protein 3 and to characterize its biologic activities as a sperm
      ligand and an inducer of the acrosome reaction. STUDY DESIGN: Human ovarian
      teratocarcinoma (PA-1) cells were transfected with an expression vector
      containing human zona pellucida protein 3 complementary deoxyribonucleic acid
      with a sequence coding for a 6-histidine tail introduced into its 3' end.
      Purification of the secreted glycoprotein was performed by sequential affinity
      (lectin and nickel--nitrilotriacetic acid) and ion-exchange chromatography.
      RESULTS: Western blot analysis confirmed a molecular weight of approximately 65
      kd for the purified product. A cell-free translation system revealed a correctly
      sized protein backbone of 47 kd. The recombinant human zona pellucida protein 3
      demonstrated specific, potent, and dose-dependent competitive inhibition of sperm
      zona pellucida binding in vitro under hemizona assay conditions. Recombinant
      human zona pellucida protein 3 also stimulated the acrosome reaction of live
      sperm. This effect was fast, dose dependent, and capacitation time dependent.
      Furthermore, advance incubation with pertussis toxin, an inactivator of
      heterotrimeric G proteins, blocked recombinant human zona pellucida protein 3-
      induced acrosomal exocytosis. CONCLUSION: The recombinant human zona pellucida
      protein 3 expressed in PA-1 cells manifested the full spectrum of expected
      biologic activities. It therefore represents a valuable tool for examination of
      human fertilization and the design of new strategies in diagnosis of male factor
      infertility and in contraception.

PMID- 11303191
TI  - Predictors of the vaginal microflora.
AB  - OBJECTIVE: Our purpose was to define influences on the patterns of the vaginal
      microflora. STUDY DESIGN: We enrolled 617 African American and Mexican American
      women in a 1-year longitudinal study of sexual behaviors and the vaginal
      microflora on the basis of the presence of gonorrhea, chlamydial infection,
      trichomoniasis, or syphilis at the initial visit. The patients were assigned
      randomly to a behavioral intervention or standard counseling regarding sexually
      transmitted disease. We reevaluated 508 (82%) and 549 (89%) women at 6 and 12
      months, respectively. A comprehensive survey of lower genital tract organisms was
      conducted at baseline and at 6 and 12 months. Behavioral and microbiologic
      associations were screened by bivariate analysis. All variables associated with
      an organism at P < or = .15 were included in a multivariate analysis.
      Associations between behavior and the genital tract microflora were identified by
      logistic regression coefficients with P <.05. RESULTS: African American race had
      a consistent association with vaginal microflora, specifically, Mycoplasma
      hominis, Trichomonas vaginalis, bacterial vaginosis, group B streptococci,
      Neisseria gonorrhoeae, and Chlamydia trachomatis. Various behaviors had a less
      consistent effect, including multiple partners, douching, frequency of coitus >3
      times a week, and cunnilingus, fellatio, and anal intercourse at the last sexual
      encounter. M hominis (but not Ureaplasma urealyticum ), Gardnerella vaginalis,
      and Lactobacillus species were associated with bacterial vaginosis. Lactobacillus
      species appeared to protect against bacterial vaginosis and infection with G
      vaginalis. Sexually transmitted diseases (caused by M hominis, N gonorrhoeae, C
      trachomatis, and T vaginalis ) were associated with each other. In contrast,
      hormonal status, vaginal blood, and foreign bodies had little effect. CONCLUSION:
      The presence of other microorganisms and race have a more consistent association
      with the presence or absence of a cervical-vaginal organism than sexual behavior,
      hormonal status, vaginal devices, or the presence of abnormal vaginal bleeding.

PMID- 11303192
TI  - Clinical predictors of endometritis in women with symptoms and signs of pelvic
      inflammatory disease.
AB  - OBJECTIVE: Careful detection and treatment of pelvic inflammatory disease are
      essential for the prevention of adverse sequelae. The purpose of this study was
      to evaluate the diagnostic test characteristics of clinical criteria for the
      diagnosis of pelvic inflammatory disease. STUDY DESIGN: We performed a cross
      sectional analysis of the baseline characteristics of 651 patients enrolled in a
      multicenter randomized treatment trial for pelvic inflammatory disease. Clinical
      and laboratory findings were recorded for all patients, and endometrial sampling
      was performed. We calculated sensitivity and specificity and performed receiver
      operating characteristic curve analysis and multivariate logistic regression,
      using histologic endometritis as the criterion standard. RESULTS: The minimal
      criteria for pelvic inflammatory disease, as recommended by the Centers for
      Disease Control and Prevention, had a sensitivity of 83%, in comparison with a
      95% sensitivity for adnexal tenderness (P =.001). Of the supportive clinical
      criteria, the finding most highly associated with endometritis was a positive
      test result for Chlamydia trachomatis or Neisseria gonorrhoeae (adjusted odds
      ratio, 4.3; 95% confidence interval, 2.89--6.63). A multivariate logistic
      regression model indicated that combinations of criteria significantly improve
      the prediction of endometritis. CONCLUSION: Sensitivity can be maximized by using
      the presence of adnexal tenderness as a minimal criterion for the diagnosis of
      pelvic inflammatory disease, and supportive criteria are helpful in estimating
      the probability of endometritis.

PMID- 11303193
TI  - Quantification of immunoglobulins and cytokines in human cervical mucus during
      each trimester of pregnancy.
AB  - OBJECTIVES: Our aims were to determine immunoglobulin and cytokine levels in
      cervical mucus obtained from women during each trimester of pregnancy and to
      compare these levels with those reported in normally menstruating women and in
      women taking oral contraceptives. STUDY DESIGN: Cervical mucus samples were
      collected at specified intervals from 36 pregnant women. An enzyme-linked
      immunosorbent assay was used to quantitate the presence of immunoglobulins A and
      G and interleukins 1 beta, 6, and 10 in cervical mucus. RESULTS: Immunoglobulin A
      in cervical mucus remained stable during each trimester of pregnancy (26 mg/dL).
      Cervical mucus immunoglobulin G decreased from a first-trimester high of 44.4
      mg/dL to lower levels in the second and third trimesters. Levels of interleukin 1
      beta increased significantly from the first trimester (4261 pg/mL) to 12,899
      pg/mL in the second trimester (P <.01). CONCLUSION: These data suggest a possible
      correlation of reproductive hormones and immunologic factors in the female
      reproductive tract during pregnancy.

PMID- 11303194
TI  - The moral foundation of medical leadership: the professional virtues of the
      physician as fiduciary of the patient.
AB  - Leadership in medicine, as in other settings, should be based on values that
      provide appropriate direction for the use of institutional power and authority.
      Leadership also requires managerial competence. Managerial knowledge and skills
      can be used for worthy and unworthy goals and therefore require a moral
      foundation. Using the methods of ethics, we argue that the concept of the
      physician as the moral fiduciary of the patient should be the moral foundation of
      management decisions by physician-leaders. We take this concept from the history
      of eighteenth century medical ethics and develop it in terms of four professional
      virtues--self-effacement, self-sacrifice, compassion, and integrity. We apply
      these four virtues to show how physician-leaders should create a moral culture of
      professionalism in health care organizations. We then identify four vices-
      unwarranted bias, primacy of self-interest, hard-heartedness, and corruption-
      that undermine this moral culture of professionalism. Because health care
      organizations now play a central role in patient care, their moral culture and
      therefore physician-leaders have become vital elements in physicians being able
      to maintain their professionalism. Physician-leaders bear major responsibility to
      shape organizational cultures that support the fiduciary professionalism of
      physicians.

PMID- 11303195
TI  - Postpartum sexual functioning and its relationship to perineal trauma: a
      retrospective cohort study of primiparous women.
AB  - OBJECTIVE: Our goal was to evaluate the relationship between obstetric perineal
      trauma and postpartum sexual functioning. STUDY DESIGN: Our study was carried out
      with a retrospective cohort design in 3 groups of primiparous women after vaginal
      birth: Group 1 (n = 211) had an intact perineum or first-degree perineal tear;
      group 2 (n = 336) had second-degree perineal trauma; group 3 (n = 68) had third-
      or fourth-degree perineal trauma. These sample sizes reflect a 70% response rate.
      Outcomes were time to resuming sexual intercourse, dyspareunia, sexual
      satisfaction, sexual sensation, and likelihood of achieving orgasm. RESULTS: At 6
      months post partum about one quarter of all primiparous women reported lessened
      sexual sensation, worsened sexual satisfaction, and less ability to achieve
      orgasm, as compared with these parameters before they gave birth. At 3 and 6
      months post partum 41% and 22%, respectively, reported dyspareunia. Relative to
      women with an intact perineum, women with second-degree perineal trauma were 80%
      more likely (95% confidence interval, 1.2--2.8) and those with third- or fourth
      degree perineal trauma were 270% more likely (95% confidence interval, 1.7--7.7)
      to report dyspareunia at 3 months post partum. At 6 months post partum, the use
      of vacuum extraction or forceps was significantly associated with dyspareunia
      (odds ratio, 2.5; 95% confidence interval, 1.3--4.8), and women who breast-fed
      were > or = 4 times as likely to report dyspareunia as those who did not breast
      feed (odds ratio, 4.4; 95% confidence interval, 2.7--7.0). Episiotomy conferred
      the same profile of sexual outcomes as did spontaneous perineal lacerations.
      CONCLUSIONS: Women whose infants were delivered over an intact perineum reported
      the best outcomes overall, whereas perineal trauma and the use of obstetric
      instrumentation were factors related to the frequency or severity of postpartum
      dyspareunia, indicating that it is important to minimize the extent of perineal
      damage incurred during childbirth.

PMID- 11303196
TI  - p53 Mutations and microsatellite instability in ovarian cancer: Yin and yang.
AB  - OBJECTIVE: We tested the hypothesis that p53 frameshift mutations in ovarian
      cancer occur as a result of genomic instability rather than as a proximal cause
      of this process. STUDY DESIGN: Sequencing of the p53 tumor suppressor gene has
      been carried out on 305 ovarian, fallopian tube, and peritoneal cancers. Two
      groups of p53 null mutations were identified: (1) those caused by frameshift
      insertion or deletion mutations (n = 31) and (2) those caused by nonsense
      mutations (n = 28). As a control group 59 tumors with p53 missense mutations were
      selected by matching with the p53 null tumors on the basis of patient age at
      diagnosis, stage and grade of cancer, cancer site, and year of diagnosis.
      Microsatellite instability was determined from paired normal and tumor tissue
      deoxyribonucleic acid by means of the following different markers: D2S123,
      D5S346, D17S250, BAT25, and BAT26. Amplimers from polymerase chain reactions were
      evaluated on 7% polyacrylamide gels. RESULTS: The p53 null tumors were more
      likely to be of higher stage and grade. Fallopian tube cancers were more common
      (P =.02) in the p53 frameshift group. The overall incidence of microsatellite
      instability was 39%, 36%, and 25% for tumors with p53 frameshift nonsense and
      missense mutations (P =.30). Microsatellite instability was seen almost
      exclusively with ovarian cancer (P =.04). CONCLUSIONS: Microsatellite instability
      is a relatively common event in ovarian cancer and is dependent on marker
      selection. The p53 frameshift mutations do not appear to occur as a consequence
      of genomic instability.

PMID- 11303197
TI  - Randomized comparison between orally and transdermally administered hormone
      replacement therapy regimens of long-term effects on 24-hour ambulatory blood
      pressure in postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to assess whether oral delivery and
      transdermal delivery of sequential combined hormone replacement therapy have
      similar effects on systemic blood pressure, as measured by 24-hour automated
      ambulatory recordings. STUDY DESIGN: Eighty-two healthy postmenopausal women, of
      whom 73 completed the study, were randomly assigned to start hormone replacement
      therapy with either orally (n = 38) or transdermally (n = 35) administered
      medication. Ambulatory blood pressure was recorded for a 24-hour period before
      the start of hormone replacement therapy and again 2 and 6 months later. Analysis
      of variance was used for data analysis. RESULTS: Hormone replacement therapy by
      both oral and transdermal routes was associated with slight but nonsignificant
      drops in mean 24-hour systolic and diastolic ambulatory blood pressure. Daytime
      systolic ambulatory blood pressure (mean +/- SE) fell significantly (P <.05) and
      similarly at 2 months in the oral (3.8 +/- 0.2 mm Hg) and transdermal (4.0 +/-
      0.3 mm Hg) treatment groups. The daytime ambulatory blood pressure remained
      significantly lower than baseline at 6 months in the oral treatment group (-3.6
      +/- 0.3 mm Hg), whereas the fall at 6 months in the transdermal group (-3.1 +/-
      0.3 mm Hg) was not significant. Mean daytime diastolic ambulatory blood pressure
      was reduced in both the oral (-1.8 +/- 0.8 mm Hg) and transdermal (-3.5 +/- 0.7
      mm Hg; P <.05) treatment groups at 2 months but not at 6 months. Nighttime
      ambulatory blood pressures in both groups remained unaffected by hormone
      replacement therapy. CONCLUSION: Sequential combined hormone replacement therapy
      delivered by both oral and transdermal routes caused significant falls in the
      daytime ambulatory blood pressure of normotensive postmenopausal women at 2
      months of treatment. This fall persisted as long as 6 months of treatment in the
      oral treatment group but not in the transdermal treatment group.

PMID- 11303198
TI  - Effects of 15 months of 17 beta-estradiol and dydrogesterone on systolic cardiac
      function according to quantitative and Doppler echocardiography in healthy
      postmenopausal women.
AB  - OBJECTIVE: Our goal was to investigate the short-term and intermediate effects of
      low-dose hormone replacement therapy on echocardiographic parameters of cardiac
      function in healthy postmenopausal women. STUDY DESIGN: In a prospective,
      controlled study 30 healthy postmenopausal women (mean age, 52 +/- 3 years) were
      randomly assigned to 2 groups. Women in the hormone replacement therapy group (n
      = 15) received 1 mg micronized 17 beta-estradiol daily sequentially combined with
      5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and
      thereafter 2 mg 17 beta-estradiol combined with 10 mg dydrogesterone for a period
      of 3 months. The control group (n = 15) received no treatment. M-mode,
      quantitative 2-dimensional, and Doppler echocardiographic measurements were
      performed at baseline and within the 17 beta-estradiol phase at 3, 12, and 15
      months. RESULTS: After 12 months significant differences in change between the 2
      groups were found for left ventricular end-diastolic and left ventricular end
      systolic diameters, left ventricular mass index, and stroke volume index. These
      differences were caused by changes in the control group rather than in the
      hormone replacement therapy group, in which no significant within-group changes
      were found. All other parameters measured showed no effect. CONCLUSION: Within 15
      months of 17 beta-estradiol and dydrogesterone treatment no clinically relevant
      differences were found in the M-mode, quantitative 2-dimensional, and Doppler
      echocardiographic parameters measured in this study. It is suggested that 15
      months of treatment probably is too short a period for detection of direct
      effects on the heart itself.

PMID- 11303199
TI  - Effect of menstruation and intrapelvic injection of endometrium on inflammatory
      parameters of peritoneal fluid in the baboon (Papio anubis and Papio
      cynocephalus).
AB  - OBJECTIVE: Our purpose was to test the hypothesis that menstruation and
      intrapelvic injection of endometrium for the induction of endometriosis affect
      inflammatory parameters in peritoneal fluid from baboons. STUDY DESIGN: In the
      first part of this study, 107 laparoscopies were performed in 62 female baboons
      with a normal pelvis during menstruation, the follicular phase, and the luteal
      phase. In the second part of this study, 21 baboons were studied during paired
      laparoscopies in the follicular phase and the luteal phase of the cycle. In the
      third part of this study, 11 baboons were studied by paired laparoscopies during
      menses and during the nonmenstrual phase of the cycle. In the fourth part of this
      study, paired laparoscopies were performed in 7 baboons before and after
      intrapelvic injection of endometrium. Peritoneal fluid was aspirated and measured
      in all laparoscopies and assessed for leukocyte concentration. In the third and
      fourth parts of the study, peritoneal fluid was analyzed for the concentrations
      of inflammatory cytokines and for the proportions of cells with
      immunohistochemical staining positive for these cytokines. RESULTS: During
      menstruation, in comparison with nonmenstrual phases of the cycle, the leukocyte
      concentration of the peritoneal fluid was increased significantly, as were the
      proportions of peritoneal fluid cells with positive staining for tumor necrosis
      factor alpha, transforming growth factor beta(1), and intercellular adhesion
      molecule 1 and the peritoneal fluid concentrations of transforming growth factor
      beta(1) and interleukin 6. After intrapelvic injection of endometrium, the
      peritoneal fluid leukocyte concentration and the proportions of peritoneal fluid
      cells with positive staining for tumor necrosis factor alpha, transforming growth
      factor beta(1), CD3, and human leukocyte antigen (DR locus) significantly
      increased. CONCLUSION: Subclinical peritoneal inflammation occurs in baboons
      during menstruation and after intrapelvic injection of endometrium.

PMID- 11303200
TI  - Transdermal estrogen reduces vascular resistance and serum cholesterol in
      postmenopausal women.
AB  - OBJECTIVE: Our aim was to compare the effects of transdermal versus oral
      estrogens on vascular resistance index, mean arterial pressure, serum lipid
      concentrations, norepinephrine, and left ventricular structure. STUDY DESIGN: Ten
      postmenopausal women received transdermal estradiol (0.05 mg/d) plus cyclic oral
      progesterone for 6 months. Responses were compared with those of 23 women
      receiving oral conjugated estrogens (0.625 mg/d) plus cyclic progesterone and
      with those of 9 subjects receiving placebo in a concurrent randomized trial. We
      assessed the vascular resistance index and the mean arterial pressure at rest and
      during behavioral stressors. RESULTS: Oral and transdermal estrogen significantly
      decreased the vascular resistance index, mean arterial pressure, norepinephrine,
      and total and low-density lipoprotein cholesterol to a similar extent. Changes in
      the vascular resistance index and mean arterial pressure were equally evident at
      rest and during stress. Although both treatments reduced left ventricular mass (
      4% to -6%) and relative wall thickness (-3% to -5%), these changes were not
      statistically significant. CONCLUSIONS: Equivalent reductions in vascular
      resistance index, norepinephrine, mean arterial pressure, and cholesterol were
      observed with transdermal and oral estrogens. Future studies comparing novel
      hormone regimens with oral hormone replacement therapy should include multiple
      risk markers to allow better assessment of their potential impact on coronary
      artery health.

PMID- 11303201
TI  - Risks of smoking to reproductive health: assessment of women's knowledge.
AB  - OBJECTIVE: Our aim was to assess the knowledge of women regarding the gender
      specific health risks associated with smoking. STUDY DESIGN: A cross-sectional
      survey was given to 388 female hospital employees. Knowledge of smoking-related
      illnesses that are specific to women was assessed. Regression analysis was used
      to discern potential predictors of this knowledge. RESULTS: Most women are aware
      that smoking causes respiratory disease (99%), lung cancer (99%), heart disease
      (96%), and pregnancy complications (91%). Few women are aware of the health risks
      of smoking that are specific to women, such as infertility (22%), osteoporosis
      (30%), early menopause (17%), spontaneous abortion (39%), ectopic pregnancy
      (27%), and cervical cancer (24%). Knowledge of these health risks was not
      predicted by age, education, or smoking status. Health care professionals were no
      more likely than other women to have knowledge of these risks. CONCLUSION: Most
      women are unaware of the health risks specific to women from smoking. Even female
      health care professionals do not generally have greater knowledge of these
      conditions. Further public health measures are necessary to increase knowledge of
      smoking risks that may be particularly relevant to women. This increase in
      knowledge has the potential to reduce significantly the smoking-related illnesses
      in women.

PMID- 11303202
TI  - Value of human papillomavirus deoxyribonucleic acid testing after conization in
      the prediction of residual disease in the subsequent hysterectomy specimen.
AB  - OBJECTIVE: Our aim was to evaluate human papillomavirus deoxyribonucleic acid
      testing after conization in predicting residual disease in the subsequent
      hysterectomy specimen. STUDY DESIGN: A prospective study was conducted on 75
      patients with grade 3 cervical intraepithelial neoplasia who had cone margins or
      endocervical curettage specimens showing disease and who elected to undergo
      hysterectomy after conization. All patients underwent high-risk human
      papillomavirus deoxyribonucleic acid testing by the Hybrid Capture II (Digene
      Corporation, Gaithersburg, MD) system before conization and at the time of
      hysterectomy (within 2-7 weeks after conization). The presence of human
      papillomavirus deoxyribonucleic acid in cells obtained by endocervical brush
      before hysterectomy was correlated with residual disease in the hysterectomy
      specimens. RESULTS: Of the 92 patients enrolled, 75 were eligible. Of these 75
      patients, 52 (69.3%) had persistent human papillomavirus deoxyribonucleic acid
      after conization, and 27 (36.0%) of the 75 patients had residual cervical
      neoplasia in the hysterectomy specimens. Those with negative results for human
      papillomavirus deoxyribonucleic acid after conization were all (23/23) without
      residual disease in the uterus (100% negative predictive value). All those who
      had residual disease (27/27) had positive results for human papillomavirus
      deoxyribonucleic acid at the time of hysterectomy (100% sensitivity).
      Postconization human papillomavirus deoxyribonucleic acid status (odds ratio,
      4.000; 95% confidence interval, 1.531-10.449; P =.005) and grade of dysplasia
      after endocervical curettage (classified as grade 2 cervical intraepithelial
      neoplasia or less severe disease vs grade 3 cervical intraepithelial neoplasia:
      odds ratio, 6.612; 95% confidence interval, 2.837-15.409; P =.0002) were
      significantly associated with residual tumor in the uterus. CONCLUSIONS: This
      prospective study confirms an excellent sensitivity and negative predictive value
      of human papillomavirus deoxyribonucleic acid testing after conization in
      predicting residual cervical neoplasia. A strategy of managing patients with
      grade 3 cervical intraepithelial neoplasia, based on postconization human
      papillomavirus deoxyribonucleic acid findings and endocervical curettage results,
      is proposed.

PMID- 11303203
TI  - The risks of spontaneous preterm delivery and perinatal mortality in relation to
      size at birth according to fetal versus neonatal growth standards.
AB  - OBJECTIVE: The aim of this study was to test the null hypothesis that size at
      birth relative to fetal or neonatal growth standards is not a significant
      variable related to the risk of spontaneous preterm delivery. STUDY DESIGN: This
      was a hospital-based cohort study of consecutive births at a tertiary care
      perinatal center from January 1, 1985, to December 31, 1996. A total of 37,377
      pregnancies met the following inclusion criteria: (1) singleton gestation, (2) 25
      to 40 weeks' gestation, and (3) no anomalies. Neonates were divided into 5 birth
      weight categories according to either fetal (uncorrected for sex) or neonatal
      (corrected for sex) growth standards, as follows: (1) intrauterine growth
      restriction, birth weight <3rd percentile; (2) borderline intrauterine growth
      restriction, birth weight > or = 3rd percentile and <10th percentile; (3)
      appropriate for gestational age, birth weight from 10th percentile through 90th
      percentile; (4) borderline large for gestational age, birth weight >90th
      percentile but < or = 97th percentile, and (5) large for gestational age, birth
      weight >97th percentile. Logistic regression analysis was used to estimate the
      independent effect of birth weight category on the risk of preterm delivery after
      spontaneous onset of labor, with the appropriate-for-gestational-age group
      serving as a reference. RESULTS: When fetal growth standards were applied, there
      was a significant increase in the risk of spontaneous preterm delivery when birth
      weight was outside the appropriate-for-gestational-age range (odds ratios of 2.5,
      1.4, 1.2, and 1.9 for intrauterine growth restriction, borderline intrauterine
      growth restriction, borderline large-for-gestational age, and large-for
      gestational-age groups, respectively). In contrast, when neonatal growth
      standards were applied, the risks of spontaneous preterm delivery in intrauterine
      growth restriction, borderline intrauterine growth restriction, and large-for
      gestational-age groups were significantly lower (odds ratios of 0.5, 0.7, and 0.7
      for intrauterine growth restriction, borderline intrauterine growth restriction,
      and large-for-gestational-age groups, respectively) because of an underestimation
      in the number of fetuses with abnormal size at birth delivered prematurely. With
      both fetal and neonatal growth standards there was a 5-to 6-fold greater risk of
      perinatal death for both preterm and term fetuses with intrauterine growth
      restriction. CONCLUSION: Fetal growth standards are more appropriate in
      predicting the impact of birth weight category on the risk of spontaneous preterm
      delivery than are neonatal growth standards. When fetal standards are applied,
      the risks of preterm birth in both extreme abnormal birth weight categories
      (intrauterine growth restriction and large for gestational age) are 2- to 3-fold
      greater than the risk among appropriate-for-gestational-age infants.

PMID- 11303204
TI  - The use of helical computed tomography in pregnancy for the diagnosis of acute
      appendicitis.
AB  - OBJECTIVE: Accurate diagnosis of acute appendicitis in pregnancy by clinical
      evaluation is difficult. A safe, reliable test was sought to decrease a delay in
      diagnosis and to avoid unnecessary invasive procedures. A helical or spiral
      computed tomographic technique has proven to be a very accurate test in the
      nonobstetric population for the identification of acute appendicitis. We report
      its use in pregnant patients with suspected acute appendicitis. STUDY DESIGN: All
      pregnant patients who were undergoing helical computed tomography at our
      institution from April 1997 to February 1998 for the suspected clinical diagnosis
      of acute appendicitis were retrospectively reviewed. Helical computed tomography
      was performed by standard departmental protocol. A positive study was reported if
      an enlarged appendix, which did not fill with contrast material, was present with
      periappendiceal inflammatory changes. Outcomes were determined by the results of
      surgery and pathologic examination or clinical follow-up. RESULTS: Seven patients
      were identified in the study period. Two patients had positive findings on
      helical computed tomography, and acute appendicitis was confirmed at laparotomy
      and by pathologic inspection. There were no further prenatal complications and
      both patients delivered at term. Five patients had a normal-appearing appendix on
      helical computed tomography, and all of these patients had resolution of their
      pain and symptoms. CONCLUSION: Helical computed tomography appears to be a
      useful, noninvasive test to accurately diagnose acute appendicitis in pregnancy.

PMID- 11303205
TI  - Vaginal application of the nitric oxide donor isosorbide mononitrate for
      preinduction cervical ripening: a randomized controlled trial to determine
      effects on maternal and fetal hemodynamics.
AB  - OBJECTIVE: Our aim was to assess the effects of vaginally administered isosorbide
      mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant
      women at term. STUDY DESIGN: We conducted a randomized controlled trial. Women
      were randomly selected to receive vaginally administered isosorbide mononitrate,
      20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n =
      12). Maternal pulse, blood pressure, and fetal heart rate were recorded at
      baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance
      index and pulsatility index measurements were performed at 0, 180, and 330
      minutes. RESULTS: Maternal pulse rate was greater after the administration of
      isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal
      examination-only group (greatest difference in means, 21 beats/min; P <.01).
      Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40
      mg isosorbide mononitrate groups than in the vaginal examination-only group
      (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm
      Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater
      in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide
      mononitrate group or the vaginal examination-only group (difference in mean, 15
      beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia
      or maternal hypotension. Neither dose of isosorbide mononitrate had a significant
      effect on umbilical artery resistance or pulsatility index. CONCLUSIONS: Vaginal
      administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term
      has an effect on both maternal and fetal hemodynamics, but this effect is not
      clinically significant.

PMID- 11303206
TI  - Postpartum metabolism and autoantibody markers in women with gestational diabetes
      mellitus diagnosed in early pregnancy.
AB  - OBJECTIVE: Our purpose was to study postpartum metabolism and autoantibody
      markers of type 1 diabetes mellitus in women with gestational diabetes mellitus
      diagnosed in early pregnancy. STUDY DESIGN: Thirty women with gestational
      diabetes diagnosed in early pregnancy were compared with 72 women who had
      gestational diabetes diagnosed in late pregnancy. Glucose tolerance, parameters
      of carbohydrate and lipid metabolism, and antibodies to glutamic acid
      decarboxylase and to islet cells were measured. RESULTS: The percentages of overt
      diabetes and abnormal glucose tolerance were significantly higher in the early
      pregnancy group (26.7% vs 1.4%; P =.0002; and 40% vs 5.56%; P <.0001;
      respectively). Only 1 woman had positive test results for antibodies to the islet
      cells. The rate of positive test results for antibodies to glutamic acid
      decarboxylase was similar in both groups (13.7% vs 9.3%). CONCLUSIONS: Women with
      early gestational diabetes have an increased risk of postpartum diabetes
      mellitus, whereas those with late-onset gestational diabetes have a minimal risk.
      In women predisposed to type 1 diabetes, gestational diabetes develops either
      early or late in pregnancy.

PMID- 11303207
TI  - Endothelium dependence and gestational regulation of inhibition of vascular tone
      by magnesium sulfate in rat aorta.
AB  - OBJECTIVE: The aim of this study was to investigate the role of nitric oxide in
      the vasorelaxant effect of magnesium sulfate during pregnancy. STUDY DESIGN:
      Segments of 3 mm of the aorta, with or without intact endothelium, from 16- or 22
      day-pregnant rats were mounted in organ chambers with standard Krebs solution or
      low-magnesium Krebs solution for measurement of isometric tension. The rings were
      contracted with phenylephrine, and cumulative concentration-response curves for
      magnesium were determined after incubation with various inhibitors. RESULTS:
      Magnesium relaxed the aortic rings from pregnant rats in a concentration
      dependent manner. The relaxation was significantly lower on day 22 of gestation
      than on day 16 of gestation. Removal of the endothelium or incubation with 10(-4)
      mol/L N omega-nitro-L -arginine methyl ester (a nitric oxide synthase inhibitor),
      10(-5)-mol/L 6-anilino-5,8-quinolinedione (a guanylate cyclase inhibitor), or 10(
      5)-mol/L indomethacin (a cyclooxygenase inhibitor) significantly decreased the
      relaxant effect of magnesium on aortic rings from 16-day-pregnant but not 22-day
      pregnant rats. Treatment with minimally effective concentrations of a nitric
      oxide donor (3 x 10(-10)-mol/L sodium nitroprusside) or a cyclic guanosine
      monophosphate analog (10(-6)-mol/L 8-bromo-cyclic guanosine monophosphate)
      restored the response to magnesium. CONCLUSIONS: The relaxant effect of magnesium
      on rat aortic rings was dependent on both endothelium and gestational age and was
      lower at term than during late pregnancy. The endothelium appears to potentiate
      the vasorelaxant effects of magnesium through the nitric oxide-cyclic guanosine
      monophosphate and cyclooxygenase systems.

PMID- 11303208
TI  - Mild gestational hypertension remote from term: progression and outcome.
AB  - OBJECTIVE: Limited information is available regarding the progression of disease
      in women with mild gestational hypertension. Our purpose was to describe the
      prognostic signs in the natural course of mild gestational hypertension and
      pregnancy outcomes in women who were remote from term with mild gestational
      hypertension that was expectantly managed. STUDY DESIGN: Women with mild
      gestational hypertension participating in an outpatient hypertension monitoring
      program were studied. Inclusion criteria were patients with a singleton pregnancy
      between 24 and 35 weeks' gestation who had no proteinuria by dipstick (0 or
      trace) on the first 2 days of program participation. Progression to preeclampsia
      was the primary outcome. The rate of progression to severe preeclampsia,
      obstetric complications, and neonatal outcomes were secondary measures. Data were
      compared by independent Student t and Fisher exact tests where applicable.
      RESULTS: A total of 748 patients were studied during the observation period;
      preeclampsia (persistent proteinuria > or = 1+) developed in 343 (46%), and 72
      (9.6%) had antepartum progression to severe preeclampsia. No significant
      differences in maternal age, race, marital status, or tobacco use were observed
      between those women in whom persistent proteinuria developed and those in whom it
      did not develop. Gestational age of the infants at delivery (36.5 +/- 2.4 vs 37.4
      +/- 2.0 weeks), birth weight (2752 +/- 767 vs 3038 +/- 715 g), incidence of small
      for-gestational-age newborns (24.8% vs 13.8%), and duration of neonatal hospital
      stay (7.1 +/- 10 vs 5.0 +/- 9.3 days) differed significantly in the patients with
      versus those without proteinuria (P <.001 for all). CONCLUSIONS: In patients with
      mild gestational hypertension remote from term, 46% ultimately had preeclampsia,
      with progression to severe disease in 9.6%. The development of proteinuria is
      associated with an earlier gestational age at delivery, lower birth weight, and
      an increased incidence of small-for-gestational age newborns.

PMID- 11303209
TI  - Conditioned medium from hypoxic cytotrophoblasts alters arterial function.
AB  - OBJECTIVE: Our goal was to test the hypothesis that cytotrophoblasts, under low
      oxygen tension, release substances that affect vascular behavior. STUDY DESIGN:
      We studied the vascular response to the vasoconstrictors phenylephrine (receptor
      dependent) and potassium (receptor independent), the relaxation response to
      methacholine, and the vasomotor behavior of isolated resistance (mesenteric)
      arteries from early pregnant rats after incubation in conditioned medium from
      first-trimester cytotrophoblasts, maintained in standard or hypoxic (2%; 14 mm
      Hg) culture conditions. RESULTS: After incubation in medium from hypoxic
      cytotrophoblasts, arterial segments were more responsive to phenylephrine and to
      potassium-induced constriction but were less responsive to methacholine, and the
      vasomotor activity was increased compared with that found in vessels incubated in
      control medium. CONCLUSIONS: These changes in vascular behavior are similar to
      those reported in isolated arteries from women with preeclampsia. These studies
      provide evidence which suggests that the link between abnormal placentation and
      maternal vascular abnormality in preeclampsia is the elaboration of vasoactive
      factors by cytotrophoblasts in response to hypoxia.

PMID- 11303210
TI  - HLA-G expression in trophoblast cells circulating in maternal peripheral blood
      during early pregnancy.
AB  - OBJECTIVE: The aim of this study was to assess the use of circulating trophoblast
      cells in maternal peripheral blood for noninvasive prenatal diagnosis of numeric
      chromosomal aberrations. STUDY DESIGN: A combined procedure for
      immunocytochemical identification and deoxyribonucleic acid fluorescence in situ
      hybridization was used after a single enrichment step consisting of density
      gradient centrifugation. A specific HLA-G monoclonal antibody was used in
      combination with X and Y chromosome specific probes in deoxyribonucleic acid
      fluorescence in situ hybridization to confirm fetal identity of cells bearing HLA
      G in the case of a male fetus. RESULTS: We detected fetal trophoblast cells
      expressing HLA-G in maternal blood starting at 9 weeks' gestation. In addition to
      fetal sex prediction with X and Y chromosome-specific probes, fetal aneuploidy
      was confirmed in peripheral blood from a pregnancy complicated by trisomy 21.
      CONCLUSION: Although the numbers of fetal cells were extremely low, the proof of
      concept was demonstrated. Early noninvasive prenatal screening for numeric
      chromosomal abnormalities with fetal trophoblast cells is feasible.

PMID- 11303211
TI  - Evaluation of respiratory gases and acid-base gradients in human fetal fluids and
      uteroplacental tissue between 7 and 16 weeks' gestation.
AB  - OBJECTIVE: Our purpose was to evaluate the changes in intrauterine gases and acid
      base gradients inside the human fetoplacental unit at 7 to 16 weeks' gestation.
      STUDY DESIGN: Respiratory gases and acid-base values were recorded by means of a
      multiparameter sensor and samples from inside the exocoelomic or amniotic cavity,
      placental tissue, decidua, and fetal blood of 30 early pregnancies. RESULTS:
      Before 11 weeks' gestation, placental PO(2) was 2.5 times lower than decidual
      PO(2). The PO(2) increased independently at both sites during gestation, but a
      PO(2) gradient of 13.3 mm Hg persisted during the fourth month. At 13 to 16
      weeks, PO(2), oxygen saturation, and oxygen content gradients were observed
      between the fetal blood and the placenta and between the placenta and underlying
      decidual tissue. There was no fetoplacental gradient for pH and PCO(2) between 7
      and 16 weeks, but fetal blood pH values were much lower and fetal PCO(2) values
      were much higher than those reported in older fetuses. CONCLUSIONS: Early human
      placental tissue develops in a physiologically low-oxygen environment compared
      with uterine tissue. This may be necessary to allow specific placental metabolic
      activities and to protect both placental and fetal tissues against toxic oxygen
      metabolites.

PMID- 11303212
TI  - Pregnancy outcome in women with preterm labor symptoms without cervical change.
AB  - OBJECTIVE: This study was undertaken to determine pregnancy outcome in women who
      have preterm labor symptoms without cervical change according to fetal
      fibronectin status. STUDY DESIGN: Patients who were examined at the obstetric
      emergency department with symptoms of preterm labor but without cervical change
      underwent fetal fibronectin collection. Pregnancy outcome and fetal fibronectin
      results were analyzed after delivery. RESULTS: Of the 235 patients sampled, 20%
      (n = 48) had positive fetal fibronectin results. The mean +/- SD gestational age
      at delivery was lower in women with positive fetal fibronectin results (34.2 +/-
      4.1 vs 37.7 +/- 2.3 weeks; P <.001); these women were more likely to deliver
      preterm as a result of preterm labor than women with other obstetric indications
      (46% vs 19%; P <.001). Infants born to these women demonstrated lower birth
      weight (2317 +/- 895 g vs 2877 +/- 557 g; P =.003), were more likely to be
      admitted to the neonatal intensive care unit (42% vs 14%; P <.001), and were more
      likely to die in the neonatal period (11% vs 0%; P <.001). CONCLUSION: Patients
      with symptoms of preterm labor but without cervical change who have negative
      fetal fibronectin results are less likely to deliver preterm. Therefore in women
      with symptoms but without cervical change fetal fibronectin should be considered
      for risk assessment.

PMID- 11303213
TI  - Increased urinary flow without development of polyhydramnios in response to
      prolonged hypoxia in the ovine fetus.
AB  - OBJECTIVE: In the ovine fetus subjected to 24 hours of hypoxia, urinary flow is
      normal within a few hours from the onset of hypoxia and there is a maintained
      inhibition of swallowing. We hypothesized that 4 days of fetal hypoxia would lead
      to polyhydramnios. STUDY DESIGN: Five late-gestation fetal sheep were subjected
      to hypoxia for 4 days and 7 other late-gestation fetal sheep served as time
      control animals. Fetal hypoxia was produced on postsurgical days 5 through 9 by
      continuous intratracheal nitrogen insufflation to the ewe. On days 3, 5, 7, and 9
      after surgery, amniotic fluid volume, fetal urinary flow rate, and the
      compositions of maternal and fetal blood, amniotic fluid, and fetal urine were
      measured. A 3-factor analysis of variance was used for statistical analysis.
      RESULTS: During the period of experimental hypoxia the mean (+/-SE) fetal PaO(2)
      was 16.0 +/- 0.6 mm Hg, versus 21.2 +/- 0.7 mm Hg in control sheep (P <.001).
      Fetal hypoxia was associated with increased urinary flow on days 7 and 9,
      averaging 1410 +/- 310 and 2101 +/- 345 mL/d, respectively, versus 585 +/- 92 and
      699 +/- 78 mL/d, respectively, in control animals (P <.001). Amniotic fluid
      volume was unchanged with time and averaged 960 +/- 159 mL in hypoxic fetuses on
      postsurgical days 7 through 9 and 851 +/- 130 mL in control animals (P =.60).
      Fetal blood lactate increased in the hypoxic animals, averaging 3.4 +/- 2.1
      mmol/L versus 1.6 +/- 0.3 mmol/L in control animals (P =.02). Fetal urinary
      excretions of sodium, potassium, chloride, and lactate increased significantly
      during hypoxia, by 170% to 400%. CONCLUSION: Four days of nitrogen-induced
      hypoxia in the ovine fetus resulted in excess fetal urinary flow approximating
      1000 mL/d greater than normal without the development of polyhydramnios. Because
      amniotic fluid volume did not change and hypoxia is a known inhibitor of fetal
      swallowing, we speculate that intramembranous absorption of amniotic water,
      electrolytes, and lactate increased.

PMID- 11303214
TI  - Clinical value of an antibody-dependent cell-mediated cytotoxicity assay in the
      management of Rh D alloimmunization.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical value of an
      antibody-dependent cell-mediated cytotoxicity assay relative to the indirect
      antiglobulin test titer in the management of Rh D-alloimmunized pregnancies.
      STUDY DESIGN: Data from 172 Rh D-alloimmunized pregnancies were analyzed
      retrospectively. The accuracies of the highest antibody titer and of the highest
      antibody-dependent cell-mediated cytotoxicity assay result during pregnancy to
      predict fetal and neonatal Rh disease, defined as the need for intrauterine (n =
      30) or neonatal (n = 37) blood transfusion, respectively, were assessed. RESULTS:
      At different cutoff levels with equal sensitivities the antibody-dependent cell
      mediated cytotoxicity assay consistently showed a higher specificity than the
      antibody titer for the prediction of fetal disease. No difference was found
      between the receiver operating characteristic curves of the 2 tests for the
      prediction of neonatal disease. CONCLUSIONS: Selection of patients for referral
      and invasive testing for Rh D alloimmunization may be improved with the use of an
      antibody-dependent cell-mediated cytotoxicity assay.

PMID- 11303215
TI  - Screening for the major malignancies affecting women: current guidelines.
AB  - Throughout their lifetimes, many women rely on the obstetrician-gynecologist to
      provide them with regular health care. Therefore the obstetrician-gynecologist
      should be able to provide comprehensive information regarding consensus screening
      recommendations for the major malignancies that occur in women. Additionally, a
      woman's health care provider should continually refine his or her cancer risk-
      assessment skills and should remain apprised of high-risk habits, family
      histories, and other cancer-predisposing factors that allow identification of
      those women in whom heightened surveillance or intervention may be appropriate.
      This article reviews the epidemiologic and risk factors associated with the major
      malignancies that affect women today and provides screening guidelines.

PMID- 11303216
TI  - Estrogens, progestins, selective estrogen receptor modulators, and the arterial
      tree.
AB  - We reviewed studies of the effects of different estrogens, progestins, and
      selective estrogen receptor modulators at the coronary and carotid arterial sites
      to help determine their likely effects on cardiovascular morbidity and mortality.
      All English-language studies published between 1997 and 2000 on MEDLINE, Current
      Contents, and Best Evidence were reviewed, including in vitro, other animal,
      human physiologic, and clinical trial studies. We synthesize, assess limitations,
      and integrate across systems with the in vivo experience in humans to evaluate
      the clinical context. Estrogens have favorable direct effects in most
      circumstances, progestins oppose these effects, and early studies suggest that
      selective estrogen receptor modulators are protective. In some systems the
      dosage, route of delivery, and type of progestin may be important and risk
      factors may modulate hormone effects. The evaluation of endothelial dysfunction
      gives a unique in vivo opportunity to assess the vascular properties of hormones,
      although the relationship between the in vivo physiologic effects of hormones and
      clinical outcomes remains to be determined.

PMID- 11303217
TI  - Twin discordance and indicated preterm birth.

PMID- 11303218
TI  - Twin birth weight discordance and spontaneous versus indicated preterm birth.

PMID- 11303220
TI  - Fetal reduction procedures for triplets.

PMID- 11303221
TI  - Triplets: outcomes of expectant management versus multifetal reduction for 127
      pregnancies.

PMID- 11303223
TI  - Loop excision in cases of atypical glandular cells found on routine cervical
      cytologic testing.

PMID- 11303225
TI  - Detection of child sexual abuse.

PMID- 11303227
TI  - Spontaneous preterm labor and cervical length.

PMID- 11303229
TI  - A low-molecular-weight heparin preparation contraindicated during pregnancy.

PMID- 11303230
TI  - Peritoneal endometriosis detection.

PMID- 11303232
TI  - Processing of semen from human immunodeficiency virus-seropositive men for use in
      insemination of seronegative women.

PMID- 11303233
TI  - Pregnancy, epilepsy and antiepileptic drugs.

PMID- 11303234
TI  - Acute subdural haematoma : a reappraisal.
AB  - Acute subdural haematoma is a well-entrenched nosological entity implying
      subdural collection of blood following acute head injury. Pathologically, it is
      usually associated with or, for that matter, secondary to cerebral contusion and
      laceration. Based on cumulated experience, clinical and pathological studies it
      is proposed that, for too long the neurosurgeons have put emphasis on the clot
      rather than the totality of the pathological anatomy and that they have focused
      their therapeutic strategy on removal of the accumulated blood, unmindful of the
      associated parenchymatous lesion. Not surprisingly, such attempts have been
      associated with a very high mortality. On the basis of nearly four decades of
      personal experience and critical review of the literature, evidence has been
      provided that to reduce the mortality associated with this condition, it is
      necessary to evolve a strategy, not only to evacuate the blood but
      comprehensively deal with the associated parenchymatous lesions and the cascade
      of secondary insult to the underlying brain.

PMID- 11303235
TI  - Anaesthetic and intensive care aspects of spinal injury.
AB  - Over the last few years, spinal injuries have been classified depending upon
      their causative mechanism and on the basis of three column concept of the
      structure of vertebral column. The concept of primary and secondary injury has
      laid more stress on prevention and treatment of secondary injury. Methyl
      prednisolone still remains the drug of choice for prevention of secondary injury.
      Spinal injury involves all organ systems of the body depending on the level of
      lesion. Immobilisation of injured spine and maintenance of adequate airway after
      spinal injury need immediate attention. Orotracheal intubation under general
      anaesthesia, with manual in-line traction, is still considered the best method.
      Hypotension, hypertension and hyperglycaemia should be avoided during
      anaesthesia. Care should be taken to avoid effects of autonomic hyper reflexia.
      Spinal cord functions should be monitored and, if required, induced hypotension
      can be used with adequate monitoring.

PMID- 11303237
TI  - Management of respiratory failure in severe neuroparalytic snake envenomation.
AB  - Fourteen patients with severe neuroparalytic snake envenomation, resulting in
      acute type II respiratory failure, admitted to respiratory critical care unit for
      mechanical ventilation during one year period, were studied. Ventilatory
      requirements, amount of anti snake venom (ASV) infused, period of neurological
      recovery and hospital survival were evaluated. All patients had severe
      manifestations such as ptosis, extraocular muscle paresis and limb weakness along
      with dyspnoea. Seven patients (50%) had additional complaints of dysphagia and
      dysphonia. ASV was administered to all, with a median requirement of 900 ml.
      Mechanical ventilation was required for a median duration of 17 hours and all
      except one patient, who had suffered irreversible hypoxic cerebral injury prior
      to resuscitation, survived with complete neurological recovery. We conclude, that
      the timely institution of ventilatory support and anti-venom therapy in such
      patients, is associated with an excellent outcome.

PMID- 11303236
TI  - Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an
      Indian autosomal recessive limb girdle muscular dystrophy patient :
      immunochemical analysis and clinical aspects.
AB  - Abnormalities of dystrophin are a common cause of muscular dystrophy and testing
      for dystrophin gene or protein has become a part of routine diagnostic evaluation
      of patients who present with progressive proximal muscle weakness, high serum
      creatine kinase concentrations, and histopathological evidence of a dystrophic
      process. Patients who have no dystrophin abnormalities are assumed to have
      autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2
      mentally normal brothers presented with abnormal gait and protrusion of chest and
      hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy
      binding of dystrophin. No detectable deletion was observed in the patient's DNA
      and his brother with cDMD probes. Dystrophin associated proteins, beta
      dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha
      sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta
      sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal
      molecular weight but of decreased quantity, beta-dystroglycan was reduced by
      about 37% while alpha-sarcoglycan was completely absent. This study is a first
      attempt for a systematic clinical, genetic and molecular investigation of the
      autosomal recessive LGMD in India.

PMID- 11303238
TI  - Retained intracranial splinters : a follow up study in survivors of low intensity
      military conflicts.
AB  - With improvements in the ballistic physics, patient evacuation, imaging,
      neurosurgical management and intensive care facilities, there has been overall
      improvement in the survival of patients with missile injuries of the brain.
      Patients with retained intracranial fragments have been followed up and the
      sequelae of such fragments were analysed. We present our observations in 43 such
      patients who had survived low velocity missile injuries of the brain during
      military conflicts and had retained intracranial fragments. Over a follow up
      period of 2 to 7 years, suppurative sequelae (brain abscess, recurrent
      meningitis) were seen in 6 patients, two of these progressing to formation of
      brain abscess. Three patients developed hydrocephalus and one seizures. Patients
      with orbitocranial or faciocranial wound of entry had a higher incidence of
      suppurative complications (3 out of 4), while those with skull vault entry had a
      lower incidence of such sequelae (7 out of 30). Nine patients were lost to follow
      up. Other determinants of suppurative complications were postoperative CSF leak
      and intraventricular lodgement of the fragment.

PMID- 11303239
TI  - Neurogenic heterotopic ossification : a diagnostic and therapeutic challenge in
      neurorehabilitation.
AB  - Heterotopic ossification (HO) is an important cause of restriction in range of
      movements and secondary motor disability following neurotrauma, orthopaedic
      interventions and burns. It has not received focussed attention in non-traumatic
      neurological disorders. In a prospective study of 377 patients, on medical
      problems in neurological rehabilitation setting, 15 subjects (3.97%) had
      neurogenic heterotopic ossification. Their clinical diagnosis was: transverse
      myelitis (7), neurotuberculosis (4), traumatic myelopathy (2) and stroke (2). Hip
      (10), knee (4) and elbow joints (1) were involved. The risk factors included
      urinary tract infection (15), spasticity (6), pressure sores (13) and deep venous
      thrombosis (DVT) (6). The initial diagnosis was often other than HO and included
      DVT (3), haematoma (2) and arthritis (2). ESR and serum alkaline phosphatase
      levels were elevated in all but one subject. The diagnosis of HO was established
      using X-rays, CT Scan and three-phase bone scan. Following treatment with non
      steroidal anti-inflammatory drugs, the range of motion improved in only four
      patients. HO resulted in significant loss of therapy time during rehabilitation.
      High index of suspicion about this complication is necessary for early diagnosis
      and prompt intervention.

PMID- 11303240
TI  - Neuropathological complications of infective endocarditis : study of autopsy
      material.
AB  - 78 autopsy proven cases of infective endocarditis (IE) seen during 1983 to 1995
      were retrospectively reviewed. The brain was available for examination in 44
      cases. In the remaining cases, brain was not examined because examination of it
      was not requested due to lack of neurological findings. Brain lesions were
      observed in 35 out of 44 cases of IE. Assuming remaining 34 cases to be without
      brain lesions, the brain involvement in IE would be 44.87% (35 out of 78 cases).
      Mean age of all cases of IE and those with brain lesions was similar i.e. 26.5+/
      16.6 years and 26.6+/-13.06 years respectively. Largest number of cases with
      neuropathological lesions were associated with normal valve IE (48.57%). Mitral
      valve was most commonly involved in cases with CNS complications (57.14%)
      (p<0.05). The various types of brain lesions were infarction (68.57%),
      haemorrhage (57.14%), cerebral micro-abscess (31.42%) and focal meningitis
      (14.28%). More than one type of lesion was observed in 19 cases, indicating
      complicated nature of brain lesions in fatal cases of IE. Left sided middle
      cerebral artery (MCA) territory was the commonest site of infarction and
      haemorrhage. Staphylococcus aureus appeared to be the most common organism in
      fatal cases of IE. Normal valve IE with or without CNS complications constitutes
      a significant group in India and is different from the west as far as the
      predisposing conditions are concerned.

PMID- 11303241
TI  - Sleep apnoea syndromes : clinical and polysomnographic study.
AB  - Sleep apnoea syndromes have been known since long, and frequently the presenting
      symptoms are neurological in nature. However, these disorders have not been
      systematically studied and reported in the Indian literature. Out of 12,000
      neurology outpatients seen by authors in 2 years, 60 had primary sleep
      disturbances. All these 60 patients underwent clinical evaluation and video EEG
      polysomnography. In 8 out of 60 (13%) patients, sleep apnoea was documented. Five
      patients had obstructive sleep apnoea, 3 had mixed sleep apnoea and none had pure
      central sleep apnoea syndrome. Three-fourths of the patients were obese (mean
      weight 82kg) middle aged males (mean age 46.3 years). The main symptoms
      encountered were excessive daytime somnolence and snoring. The symptom severity
      was found to correspond directly with the duration of symptoms as well as
      obesity. Sleep apnoea syndromes must be seriously considered and documented in
      all patients complaining of excessive daytime somnolence.

PMID- 11303242
TI  - Brainstem auditory evoked potentials in tubercular meningitis and their
      correlation with radiological findings.
AB  - The present study has been undertaken to describe brainstem auditory evoked
      potential (BAEP) changes in tubercular meningitis (TBM) and correlate these with
      CT scan and MRI findings. 24 patients with TBM were subjected to clinical
      evaluation and CT scan or MRI study. Outcome was defined by 3 month Barthel index
      score (BI) into poor (BI<12) and good (BI>or=12). The mean age of patients was
      26.4+/-14.9 (range 10-62) years, 8 of them were females. Sixteen patients were in
      stage III, 5 in stage II and 3 in stage I meningitis. CT scan revealed
      hydrocephalus in 16, exudate in 9, infarction in 12 and tuberculoma in 3
      patients. Brainstem was involved in 3 patients (2 infarction and 1 granuloma).
      BAEPs were unrecordable in one patient and abnormal in 15. The absolute latencies
      and inter peak latency (IPL) however were not significantly affected. The wave
      V/I amplitude ratio was abnormal on 12 sides. The BAEP abnormalities were not
      related to the stage of meningitis, level of consciousness, any specific CT or
      MRI changes or outcome at 3 months.

PMID- 11303243
TI  - Epileptic seizures in supratentorial gliomas.
AB  - Two hundred patients with supratentorial glioma; astrocytoma (pilocytic,
      fibrillary, gemistocytic) 82, mixed glioma (oligoastrocytoma) 46,
      oligodendroglioma 8, malignant (anaplastic) astrocytoma 33 and glioblastoma
      multiforme 31, surgically treated for the tumours and followed up for one to
      sixteen years, were retrospectively analysed for the incidence of pre and
      postoperative epileptic seizures. 122 patients (61%) had seizures preoperatively.
      62 (50.8%) of them had at least one or more seizures during follow up. Seizures
      were persistent in 22 patients. Doubtful, or one or two minor seizures occurred
      in 19 cases. Six patients in this group had seizure only at the time of CT
      confirmed recurrence, after a seizure free interval of one to nine years. Amongst
      78 patients who did not have seizures preoperatively, 24 (30.6%) developed
      seizures during the postoperative follow up period. Recurrent attacks were
      reported only by 5 patients while 15 patients had seizure(s) only at the time of
      recurrence of tumour. Two patients had a few seizures in the early postoperative
      period and none thereafter, while doubtful seizures were reported by two
      patients.

PMID- 11303244
TI  - Pregnancy in women with epilepsy : preliminary results of Kerala registry of
      epilepsy and pregnancy.
AB  - Eighty-five women with epilepsy were followed up for reproductive functions under
      the registry of epilepsy and pregnancy. 32 of them had completed the pregnancy.
      Their mean age was 26 years and mean seizure frequency was 0.7 during current
      pregnancy. Nineteen of them (59.4%) had generalized epilepsy. Nine of them were
      not on any anti epileptic drugs (AED), 23 women were on various AEDs, 19 being on
      monotherapy. Only 40% of the women were taking folic acid during pregnancy.
      Pregnancy ended as spontaneous abortion in one patient. Nearly one third required
      cesarean section. Majority (87.5%) had term babies. Three (10.7%) babies had
      birth asphyxia. Six babies (21.4%) had low birth weight. Congenital malformations
      were detected in four cases (12.5%). Malformations included neural tube defects,
      talipes equinovarus and other minor anomalies. These babies were exposed to
      sodium valproate, carbamazepine or phenobarbitone. The risk of malformation was
      significantly greater (p<0.05) when the mother had generalized epilepsy. The odds
      ratio for risk of malformation was much higher with sodium valproate (6) than
      that with carbamazepine (1.2) or phenobarbitone (0.8). Majority of women with
      epilepsy had safe pregnancy and childbirth without any aggravation of epilepsy.

PMID- 11303245
TI  - Ulnar nerve palsy due to axillary crutch.
AB  - A young lady with residual polio, using axillary crutch since early childhood,
      presented with tingling, numbness and weakness in ulnar nerve distribution of
      five months duration. Ulnar motor conduction study revealed proximal conduction
      block near the axilla, at the point of pressure by the crutch while walking.
      Distal ulnar sensory conduction studies were normal but proximal ulnar sensory
      conduction studies showed absence of Erb's point potential. These findings
      suggested the presence of conduction block in sensory fibers as well. Proper use
      and change of axillary crutch resulted in clinical recovery and resolution of
      motor and sensory conduction block.

PMID- 11303246
TI  - Intramedullary cysticercosis : MRI diagnosis.
AB  - Three cases of dorsal intramedullary cysticercosis presenting as spastic
      paraparesis or paraplegia are reported. A definite preoperative diagnosis, using
      MRI, was made in two cases while in the third it was strongly suspected. One
      paraplegic patient regained full function whereas in the other two the deficit
      persisted even after successful cyst excision. The pathogenesis and recovery are
      discussed in the light of the MRI findings.

PMID- 11303247
TI  - Utility of the cysticercus immunoblot in a patient with an atypical solitary
      cerebral cysticercus granuloma.
AB  - The value of the enzyme linked immunotransfer blot (EITB) assay in avoiding an
      invasive diagnostic procedure in a patient with an atypical solitary cerebral
      cysticercus granuloma is presented.

PMID- 11303248
TI  - The 'hook effect' on serum prolactin estimation in a patient with
      macroprolactinoma.
AB  - Large quantities of antigen in an immunoassay system impair antigen-antibody
      binding, resulting in low antigen determination. This is called the 'high dose
      hook effect'. We report this phenomenon in a patient with a large
      macroprolactinoma. In this patient, the correct estimate of serum prolactin (PRL)
      was obtained only after appropriate dilution of serum. We suggest that in order
      to avoid the high dose hook effect, the serum PRL be estimated in appropriate
      dilution in all patients with large pituitary tumours. This is particularly
      important when the clinical suspicion of high PRL is strong, as in women with
      amenorrhoea-galactorrhoea and men with long standing hypogonadism.

PMID- 11303249
TI  - Dermatofibrosarcoma protuberans of scalp : a case report.
AB  - A case of dermatofibrosarcoma protuberans of scalp involving the underlying bone,
      operated after recurrence by taking safety margin of 3 cm and skin deficit
      covered by transposition flap, is being reported. Modality of treatment has been
      discussed.

PMID- 11303250
TI  - Multiple vasculogenic disabilities : a challenge in rehabilitation.
AB  - A 37 year old male presented with left hemiplegia, left below knee amputation,
      right partial foot amputation and claudication pain. The limitations in the
      rehabilitation management in such a high-risk patient are multiplied. The
      appreciable benefits from supervised rehabilitation and judicious goal setting
      can help in improving the functional status and retard the disease progression in
      such patients. This study highlights that coexisting cerebrovascular, coronary
      and peripheral vascular diseases can pose a real challenge and can result in
      multiple disabilities.

PMID- 11303251
TI  - Single stage bilateral common carotid artery stenting in a patient of Takayasu
      arteritis.
AB  - Carotid angioplasty and stenting is increasingly becoming a safe and efficacious
      modality of treatment in the management of carotid artery stenosis. Although
      atherosclerosis is the predominant cause of this morbid disease, Takayasu
      arteritis assumes special importance in south east Asia. The diffuse nature of
      this disease with associated inflammation and scarring of the vessel make
      revascularisation difficult. We report a case of Takayasu arteritis in which a
      successful bilateral common carotid stenting was done in a single sitting.

PMID- 11303252
TI  - Cerebral abscess with astrocytoma.
AB  - A child with a right parieto-occipital astrocytoma, caped by a large acute
      pyogenic abscess with flimsy capsule, detected at emergency craniotomy, is
      presented. Patient succumbed to the disease three hours following surgery.

PMID- 11303253
TI  - Contre-coup extradural haematoma : a short report.
AB  - An extradural haematoma contralateral to impact site is reported. Review of
      literature reveals that such phenomenon is extremely rare.

PMID- 11303254
TI  - Albendazole therapy for solitary persistent cysticercus granuloma.
AB  - Use of Albendazole therapy for the treatment of patients having persisting
      intracranial solitary cysticercus granuloma is controversial. Most of the times
      these patients are treated empirically with variety of drugs for variable period.
      Some authors advocate biopsy before definitive treatment. 25 patients having
      radiologicaly persistent solitary cysticercus granuloma (>6 months) were given 15
      days course of oral albendazole (15 mg/kg body wt). Cranial CT scan was repeated
      one month after the completion of albendazole therapy. It was evaluated for
      complete resolution, partial response (> 50% decrease in size of lesion) or no
      change as compared to previous scan. 12 patients (48%) showed complete
      resolution, 4 patients (16%) showed a partial response, while 9 patients (36%)
      did not show any change on follow up. Albendazole therapy may be useful for
      patients having persistent cysticercus granuloma.

PMID- 11303255
TI  - Extramedullary astrocytoma of conus region : a short report.
AB  - A 55 year old man presented with features of cauda equina syndrome. Magnetic
      resonance imaging (MRI) showed a well demarcated intradural extramedullary tumour
      at L2 vertebra. At surgery it was found to be well encapsulated and had no
      attachment to spinal cord or root. Histopathology including immunohistochemistry
      confirmed it to be a low grade astrocytoma.

PMID- 11303256
TI  - Osteochondroma of the axis : letter to editor.

PMID- 11303257
TI  - Otogenic intracranical suppuration at a rare site - letter to editor.

PMID- 11303258
TI  - Cranio - vertebral anomaly - type II basilar invagination (Dejerine Type),
      persistent spheno - occipital synchondrosis, foramen magnum stenosis, cervical
      stenosis with chronic cervical cord atrophy.

PMID- 11303259
TI  - Seizures after stroke : a prospective clinical study.
AB  - Stroke is one of the most common causes of epilepsy in elderly. However, there
      have been very few prospective studies to define the incidence, pattern and
      outcome of seizures in stroke. Most studies are based on retrospective analysis
      of hospital records. Hence, we planned this prospective study to see the
      clinical, radiological and electroencephalographic characteristics of seizures in
      stroke and their outcome, from a north Indian tertiary care centre. Over a span
      of approximately 6 years, 269 consecutive patients with stroke were studied and
      followed up. Thirty-five (13%) of these developed seizures, primarily related to
      stroke, during mean follow up period of 15.9 months. Twenty of these had
      infarctions while 15 had haemorrhages. Involvement of the cortical region was
      seen in most of the patients with seizures. In these patients, 86% of the lesions
      involved cortical areas exclusively or in addition to subcortical areas on CT
      scan of the brain. Twenty-seven (77%) developed early seizures, two third of them
      had immediate post-stroke seizures. None of the patients with early onset
      seizures developed recurrent seizures or epilepsy, while 50% of late onset
      seizures developed epilepsy. No specific EEG pattern was found in those who later
      developed epilepsy. In the present study, early onset seizures after stroke were
      rather common and did not affect outcome and did not recur even when not treated
      with anti-epileptics. Late onset seizures were less common but were associated
      with recurrent seizures.

PMID- 11303260
TI  - Guidelines for the management of intravascular catheter-related infections.

PMID- 11303261
TI  - Safety data on meningococcal polysaccharide vaccine from the Vaccine Adverse
      Event Reporting System.
AB  - Recent recommendations by the Centers for Disease Control and Prevention's
      Advisory Committee on Immunization Practices may lead to the increased use of the
      meningococcal polysaccharide vaccine. The Vaccine Adverse Event Reporting System
      (VAERS) is useful for the detection of previously unrecognized reactions and for
      the monitoring of known reactions. Limitations of VAERS include underreporting
      and the inability to establish a causal relationship between vaccination and
      adverse events in most cases. From July 1990 through 31 October 1999, 110 adverse
      events were reported after receipt of meningococcal vaccine alone. Thirteen (12%)
      were serious, including 6 injection site reactions, 3 allergic reactions, 1 case
      of Guillain-Barre syndrome, and 3 miscellaneous events. Fever (30%), headache
      (17%), dizziness (15%), injection site hypersensitivity (13%), urticaria (12%),
      and paresthesia (10%) were among the most common events reported. Fever and
      injection site and allergic reactions are most likely causally linked to the
      vaccine. That there were few reports of serious adverse events, with >6 million
      doses having been distributed, and no clear signal of a previously unrecognized
      serious reaction is reassuring with regard to the safety of meningococcal
      vaccine.

PMID- 11303262
TI  - Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community
      acquired lower respiratory tract infections.
AB  - In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae,
      we studied 613 children aged 2-14 years who were hospitalized for community
      acquired lower respiratory tract infections (LRTIs). The patients were enrolled
      in the study by 21 centers in different regions of Italy from May 1998 through
      April 1999. Paired serum samples were obtained on admission and after 4-6 weeks
      to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal
      aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on
      admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C.
      pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children
      with M. pneumoniae and/or C. pneumoniae infections whose treatments were
      considered clinical failures 4-6 weeks after enrollment had not been treated with
      macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a
      significant role in community-acquired LRTIs in children of all ages and that
      such infections have a more complicated course when not treated with adequate
      antimicrobial agents.

PMID- 11303263
TI  - Treatment of adenovirus infections in patients undergoing allogeneic
      hematopoietic stem cell transplantation.
AB  - Retrospective analysis of 303 patients who underwent allogeneic hematopoietic
      stem cell transplantation identified 35 (11.5%) with adenovirus infection. Among
      them, 22 received specific therapy. As first-line therapy, 18 were treated with
      intravenous ribavirin, 3 with cidofovir, and 1 with vidarabine. Moreover, 2
      received donor leukocyte infusion in combination with ribavirin, and 1 received
      it after failing to respond to other therapies. Seven survived (31.8%; 3 of 13
      who received ribavirin alone and 2 of 3 who received cidofovir). Among the 5
      patients treated with combined strategies, 2 who received donor leukocyte
      infusions showed clearance of all symptoms. Acute graft-versus-host disease grade
      > or = 3 (P = .01) and a long delay between infection and treatment (P = .05)
      correlated with a greater risk of treatment failure. In conclusion, ribavirin and
      vidarabine are ineffective options, particularly for patients at who are high
      risk of acquiring disseminated adenovirus disease. Conversely, cidofovir or donor
      leukocyte infusions seem to be encouraging approaches if initiated early.

PMID- 11303264
TI  - Nontuberculous mycobacteria in patients with cystic fibrosis.
AB  - The prevalence and clinical implications of colonization with nontuberculous
      mycobacteria were prospectively studied in 37 patients who had cystic fibrosis.
      Sputum samples were cultured on Coletsos and Lowenstein-Jensen selective media
      after decontamination with sodium hydroxide and oxalic acid. Oxalic acid
      decontaminated fractions were also cultured in selective liquid medium.
      Nontuberculous mycobacteria were isolated from 6 patients (16.1%). Mycobacterium
      chelonae and Mycobacterium avium-intracellulare complex were the most common
      species. Three patients with positive results of culture had at least 1 positive
      result by acid-fast smear. Oxalic acid decontamination and culture in liquid
      medium had the lowest contamination rate (6.7%). Colonization with nontuberculous
      mycobacteria was associated with humoral response to mycobacteria (immunoglobulin
      G titers against antigen A60) in patients with samples that tested positive by
      acid-fast smear. An improvement in pulmonary function was observed in 2 patients
      after they received a course of antimycobacterial therapy. Screening for
      nontuberculous mycobacteria in patients with cystic fibrosis will contribute to
      understanding the relevance of these pathogens with regard to deterioration of
      pulmonary function in patients with cystic fibrosis.

PMID- 11303265
TI  - Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis
      and L. (V.) guyanensis in Brazil: clinical findings and diagnostic approach.
AB  - We compared the clinical findings and diagnostic methods for 66 patients with
      cutaneous leishmaniasis in the state of Bahia, Brazil, who were infected by
      Leishmania (Viannia) braziliensis (group A), with those for 68 patients in the
      state of Amazonas, Brazil, who were mainly infected by Leishmania (Viannia)
      guyanensis (group B). Differences were observed with regard to number, size, and
      location of skin lesions and to the pattern of lymphatic involvement. Patients in
      group B had smaller and more numerous lesions, which were frequently located
      above the waist, versus the larger but less numerous lesions among patients in
      group A, which were usually located on the lower limbs. Lymphatic involvement was
      present in 55 (83.3%) of the 66 patients in group A and in 42 (61.8%) of the 68
      patients in group B (P=0.005). The positivity rates of imprints and skin culture
      procedures were higher in group B. Sensitivity of in vitro culture of skin
      aspirates was 47.0% and 91.2% for groups A and B, respectively (P<.001). Although
      hamster inoculation showed similar results in both groups, the interval before
      development of disease was shorter in group B. Our data provide substantial
      evidence that indicate that the disease caused by these species differs with
      regard to clinical presentation and diagnostic approach.

PMID- 11303266
TI  - A randomized trial of ciprofloxacin versus cefixime for treatment of gonorrhea
      after rapid emergence of gonococcal ciprofloxacin resistance in The Philippines.
AB  - From 1994 through 1996-1997, high-level ciprofloxacin resistance (minimum
      inhibitory concentration [MIC], > or = 4.0 microg/mL) increased from 9% to 49% of
      gonococcal isolates recovered from consecutive female sex workers in Cebu and
      Manila, The Philippines (P < .01). During 1996-1997, 105 female sex workers with
      gonorrhea were prospectively randomized to receive treatment with oral
      ciprofloxacin, 500 mg, or cefixime, 400 mg, and followed for test of cure.
      Neisseria gonorrhoeae was reisolated within 28 days after treatment from 1 (3.8%)
      of 26 women given cefixime versus 24 (32.3%) of 72 women given ciprofloxacin (P <
      .01). Treatment failure (reisolation of pretreatment auxotype/serovar) occurred
      in 14 (46.7%) of 30 women infected with strains with MICs of ciprofloxacin > or =
      4.0 microg/mL versus 1 (3.6%) of 28 infected by strains with MICs < 4.0 microg/mL
      (P < .01). High-level, clinically significant gonococcal resistance to
      ciprofloxacin has rapidly emerged in The Philippines, and spread of
      fluoroquinolone resistance through commercial sex poses a threat to control of
      gonorrhea and prevention of human immunodeficiency virus infection and the
      acquired immunodeficiency syndrome.

PMID- 11303267
TI  - Invasive mold infections in allogeneic bone marrow transplant recipients.
AB  - Invasive mold infections (IMIs) are an important cause of morbidity and mortality
      in patients who are undergoing bone marrow transplantation (BMT). To examine the
      epidemiology, risk factors, and outcome of IMIs in allogeneic BMT recipients, all
      cases of mold infection among 94 adult patients who underwent allogeneic BMT at
      this institution from 1 January 1997 through 31 December 1998 were reviewed
      retrospectively. Fifteen cases of IMI were identified; infection occurred a
      median of 102 days after BMT. Aspergillus species was the most common cause of
      disease, and species other than Aspergillus fumigatus were present in 53% of
      patients. By multivariate analysis, the variable associated with infection risk
      was systemic glucocorticosteroid use. Prophylactic antifungal therapy that was
      targeted to high-risk patients had little effect on disease incidence. These
      observations suggest that early identification of high-risk patients and better
      approaches to prevention should be explored, to reduce incidence and severity of
      disease in this population.

PMID- 11303268
TI  - Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow
      transplantation.
AB  - Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow
      transplantation (BMT) that is mainly attributed to infection with BK virus (BKV)
      and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45
      of them developed HC. Urine samples tested positive for AdV in 26 patients, of
      which 22 showed virus type 11. Among patients who underwent allogeneic BMT,
      logistic regression analysis revealed acute graft-versus-host disease (grade, >
      or = 2) to be the most significant predictive factor for HC (P < .0001). In
      addition, a total of 193 urine samples regularly obtained from 26 consecutive
      patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and
      AdV by means of polymerase chain reaction. Of patients without HC, approximately
      30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples),
      whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients
      with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1,
      respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and
      10 of 17, respectively, when we added another 14 samples obtained from 14
      patients with HC (P < .0001, P = .026, and P < .0001, respectively). In
      conclusion, there was significant correlation between AdV and HC in the patients
      we studied.

PMID- 11303269
TI  - Tuberculin skin testing of physicians at a midwestern teaching hospital: a 6-year
      prospective study.
AB  - The epidemiology of tuberculin reactivity among physicians practicing in regions
      of moderate tuberculosis prevalence is unknown. We prospectively assessed the
      epidemiology of tuberculin skin test (TST) reactivity among physicians in
      training in St. Louis between 1992 and 1998. Of 1574 physicians who were tested,
      267 (17%) had positive TST results. Older age, birth outside of the United
      States, prior bacille Calmette-Guerin (BCG) vaccination, and practice in the
      fields of medicine, anesthesiology, or psychiatry were associated with a positive
      TST result. Among physicians born in the United States, 63 (5.7%) had positive
      TST results. Among physicians with > or = 2 documented TSTs, 12 had conversion to
      a positive TST (1.6%; 1.03 conversions per 100 person-years). Physicians in this
      study had a high rate of tuberculin reactivity, despite a low conversion rate.
      The relationship between TST conversion and birth outside of the United States
      and BCG vaccination suggests a booster phenomenon rather than true new TST
      conversions.

PMID- 11303271
TI  - Creutzfeldt-Jakob disease: recommendations for disinfection and sterilization.
AB  - Prion diseases constitute a unique infection control problem because prions
      exhibit unusual resistance to conventional chemical and physical decontamination
      methods. Recommendations to prevent cross-transmission of infection from medical
      devices contaminated by Creutzfeldt-Jakob disease (CJD) have been based primarily
      on prion inactivation studies. The recommendations in this article consider
      inactivation data but also use epidemiological studies of prion transmission,
      infectivity of human tissues, and efficacy of removing microbes by cleaning. On
      the basis of the scientific data, only critical (e.g., surgical instruments) and
      semicritical devices contaminated with high-risk tissue (i.e., brain, spinal
      cord, and eye tissue) from high-risk patients--those with known or suspected
      infection with CJD--require special treatment.

PMID- 11303270
TI  - Protein C replacement in severe meningococcemia: rationale and clinical
      experience.
AB  - Severe meningococcemia, which is associated with hemodynamic instability, purpura
      fulminans and disseminated intravascular coagulation, still has a high mortality
      rate, and patients who survive are often left invalids because of amputations and
      organ failure. Clinical studies have shown that levels of protein C are markedly
      decreased in patients with severe meningococcemia and that the extent of the
      decrease correlates with a negative clinical outcome. There is a growing body of
      data demonstrating that activated protein C, in addition to being an
      anticoagulant, is also a physiologically relevant modulator of the inflammatory
      response. The dual function of protein C may be relevant to the treatment of
      individuals with severe meningococcal sepsis. In the present review we give a
      basic overview of the protein C pathway and its anticoagulant activity, and we
      summarize experimental data showing that activated protein C replacement therapy
      clearly reduces the mortality rate for fulminant meningococcemia.

PMID- 11303272
TI  - Human herpesviruses 6 and 7 in solid organ transplant recipients.
AB  - The impact of cytomegalovirus, a member of the beta-herpesvirus subgroup of the
      Herpesviridae, on patients who have undergone transplantation cannot be
      overstated. However, in the last 15 years, 2 additional members of the human beta
      herpesvirus family have been discovered: human herpesviruses 6 and 7 (HHV-6 and
      HHV-7). The impact of HHV-6 and HHV-7 is assessed, as is the well-being of
      transplant recipients. Also discussed is whether the data on the pathological
      consequences of infection warrant routine screening for these viruses in solid
      organ transplant recipients.

PMID- 11303273
TI  - Reconstituted immunity against persistent parvovirus B19 infection in a patient
      with acquired immunodeficiency syndrome after highly active antiretroviral
      therapy.
AB  - We discovered a patient with AIDS with persistent B19 infection who had slow
      resolution of anemia after he commenced receiving HAART without intravenous
      immunoglobulin. The patient's anemia recurred when the initial course of HAART
      failed, but it remitted slowly after salvage therapy was instituted. However,
      circulating B19 was still detectable by nested polymerase chain reaction 1 year
      after commencement of salvage therapy. Immunoglobulin G and immunoglobulin M
      antibodies against B19 were not detected by means of enzyme-linked immunosorbent
      assay when the anemia initially resolved, but they were detected after the
      patient commenced receiving salvage therapy. The absence of antibody response
      after the initial remission of parvovirus B19 infection suggested that cellular
      immunity was an important component of reconstituted immune function against B19
      after the patient received HAART. The humoral response that was restored later
      was abnormal; it had strong reactivity to nonstructural protein NS-1 and poor
      generation of neutralizing antibodies against linear epitopes unique to minor
      capsid protein VP1.

PMID- 11303274
TI  - Influenza and human immunodeficiency virus infection: absence of HIV progression
      after acute influenza infection.
AB  - Influenza is a major cause of morbidity for people with significant underlying
      disease, but the impact of influenza on people infected with human
      immunodeficiency virus (HIV) remains unclear. We studied a population of HIV
      infected adults during the 1998-1999 influenza season to see whether influenza
      had any adverse effects on the course of HIV infection. During 5 months of follow
      up, we found no unique clinical manifestations or negative impact on CD4(+) cell
      count, virus load, or clinical progression of HIV disease. Although half of our
      cohort received antibiotic therapy, none received specific anti-influenza therapy
      and none required hospitalization. Acute influenza does not appear to be a risk
      for progression of HIV disease.

PMID- 11303275
TI  - Successful treatment of vancomycin-resistant Enterococcus endocarditis with oral
      linezolid.
AB  - We report a case of vancomycin-resistant Enterococcus faecium endocarditis that
      failed to respond to sequential monotherapy with chloramphenicol and
      quinupristin/dalfopristin but was successfully treated with oral linezolid.

PMID- 11303276
TI  - High carriage rate of TT virus in the cervices of pregnant women.
AB  - Prevalence studies of the recently identified TT virus (TTV) have suggested that
      parenteral transmission is a common route of infection, but other routes also
      appear likely. In this study, a high rate of cervical carriage (66%) of TTV DNA
      was found by polymerase chain reaction, which suggests that perinatal and sexual
      transmission is possible.

PMID- 11303277
TI  - Gongylonema infection of the mouth in a resident of Cambridge, Massachusetts.
AB  - We report a case of Gongylonema infection of the mouth, which caused a migrating,
      serpiginous tract in a resident of Massachusetts. This foodborne infection, which
      is acquired through accidental ingestion of an infected insect, such as a beetle
      or a roach, represents the 11th such case reported in the United States.

PMID- 11303278
TI  - Recurrent vancomycin-resistant Enterococcus bacteremia: prevalence, predisposing
      factors, and strain relatedness.
AB  - We studied the prevalence of recurrent vancomycin-resistant Enterococcus (VRE)
      bacteremia, predisposing factors, and strain relatedness during a 3 year period
      at our institution. Of 36 inpatients who had episodes of bacteremia, 3 (8.3%) had
      recurrent episodes. Predisposing factors were mucositis and neutropenia (1
      patient) and chronic renal failure requiring hemodialysis (2). Recurrent episodes
      separated by < or = 3 months were caused by identical or related strains, and
      those at greater intervals by distinct strains. Recurrent VRE bacteremia is
      uncommon.

PMID- 11303279
TI  - Probiotic Enterococcus faecium strain is a possible recipient of the vanA gene
      cluster.
AB  - The characteristics of Enterococcus faecium have led to concern regarding the
      safety of probiotics that contain this bacterium. The results of an in vitro
      filter mating assay indicate that a probiotic E. faecium strain might be a
      potential recipient of vancomycin resistance genes.

PMID- 11303280
TI  - Lessons learned from the trenches about violence.

PMID- 11303281
TI  - Benefits of psychiatric consultation-liaison nurse interventions for older
      hospitalized patients and their nurses.
AB  - Characteristics, changes in psychiatric symptoms, and discharge disposition of
      older hospitalized patients (> or =60 years) with depression or delirium after
      intervention by a Psychiatric Consultation-Liaison Nurse (PCLN) in an urban
      teaching hospital were described. A retrospective cohort design was employed
      using data from 103 clinical consultation records on older patients consecutively
      evaluated by the PCLN during a 12-month period. The Geriatric Depression Scale
      and the Confusion Assessment Method were administered by the PCLN at the first
      patient visit and again to screen-positive patients immediately before discharge.
      Thirty percent of the patients scored in the range for clinically significant
      depression and 33% screened positive for delirium at baseline. PCLN interventions
      for these patients were multifaceted and tailored to individual needs. A paired t
      test comparing the change score revealed a significant decrease in depression (p
      <.001). The proportion of those who screened positive for delirium went from 33%
      to 0% (p <.001, Chi-square test). Twelve percent of the screen-positive patients
      for either depression or delirium had improved discharge options than had been
      predicted at the time of the initial PCLN contact. A two-item consultee
      questionnaire also revealed benefits for the staff nurses caring for these older
      patients in three domains. PCLN services may benefit older hospitalized patients
      referred for depression and delirium and may contribute to positive staff nurse
      outcomes as well.

PMID- 11303282
TI  - The stratified-population-at-risk (SPAR) model for psychogeriatric nursing: a
      paradigm for the third millennium?
AB  - There is warning of a coming epidemic of older people with psychiatric problems.
      However, there are already too few specialist nurses to ensure that all older
      people receive care concordant with accepted professional standards. This problem
      is an obstacle to the World Health Organization health for all by 2000 objective.
      The Stratified Population at Risk (SPAR) model is a proactive paradigm for
      planning psychogeriatric nursing services that includes mental health promotion.
      The SPAR model assumes that-under certain conditions-all people are vulnerable to
      psychiatric problems, but differ in their level of risk. The model includes an
      innovative role for psychogeriatric nurse specialists.

PMID- 11303283
TI  - Living in the fallout: parents' experiences when their child becomes mentally
      ill.
AB  - Parental loss of a child to mental illness and the resulting grief is a
      relatively unacknowledged phenomenon. This study aimed to capture the process
      through which parents journey in the face of their child's mental illness.
      Conducting a series of focus groups, the authors sought to further the
      understanding and the needs of these families. They identify seven themes from
      initial awareness to the formation of a new stability. Identification of this
      grief process is an important step that can heighten practitioners' awareness so
      that future interventions and support systems can be developed to help these
      families deal with their pain and burden.

PMID- 11303284
TI  - Homeless patients' experience of satisfaction with care.
AB  - This article explores homeless individuals' experiences of satisfaction with
      health care, and explores the interrelationship among experiences of being
      homeless, health perceptions of participants, and experiences of satisfaction
      with health care. It presents the findings of a phenomenological study that was
      conducted using participants selected from five sites in one southeastern state.
      Participant interviews were conducted at a nurse-managed primary health care
      clinic for homeless, at a night time soup-kitchen, and at three private, not-for
      profit, homeless shelters in two different towns. The study was part of a larger
      study designed to develop and validate a reliable measure of client satisfaction
      with primary health care among homeless individuals. Face-to-face in-depth
      interviews with 17 homeless individuals were conducted, with the semistructured
      interview constituting the primary data source. Common themes were identified and
      the interrelationship of theme clusters was explored. Analysis of the data
      yielded five distinct themes that represent the lived experiences of satisfaction
      with health care. These themes were mediated and directly informed by five themes
      of homelessness and three themes of health identified in the shared experiences
      of the participants. The themes identified suggest that satisfaction with health
      care for homeless persons differs from currently identified dimensions of
      satisfaction with care, and that some aspects of homelessness are seen by
      participants as positive and health promoting.

PMID- 11303285
TI  - Might within the madness: solution-focused therapy and thought-disordered
      clients.
AB  - Nurses working with thought-disordered clients in inpatient psychiatric settings
      may find that much of their role is defined by the administration and monitoring
      of antipsychotic medications. Therefore, a challenge for these nurses can be to
      find other nursing interventions for these clients that are effective, efficient,
      and clearly and uniquely within the scope of nursing. In response to this
      challenge, this article presents the use of solution-focused therapy (SFT) to
      help thought-disordered clients better cope with some of their negative
      experiences and symptomatology. The article provides an overview of SFT, with a
      focus on how these techniques might be used on an inpatient psychiatry setting
      with clients experiencing thought disorders. The authors include three case
      studies demonstrating the use of SFT with clients experiencing thought disorders,
      and conclude with some of the lessons they have learned using SFT techniques with
      these kinds of clients in inpatient psychiatric settings.

PMID- 11303286
TI  - Recurrent autoimmune hepatitis after liver transplantation: diagnostic criteria,
      risk factors, and outcome.
AB  - Approximately 20% to 30% of patients undergoing liver transplantation for
      autoimmune hepatitis (AIH) develop features of recurrent disease. Diagnostic
      criteria for recurrent AIH are similar to those used in the nontransplanted liver
      and include, in varying combinations, biochemical, serological, and histological
      abnormalities and steroid dependency. However, these criteria are more difficult
      to apply in the liver allograft because of potential interactions between
      recurrent AIH and other complications of liver transplantation, particularly
      rejection, and the uncertain effects of long-term immunosuppression. In the
      absence of other reliable diagnostic markers, a number of studies have used the
      histological finding of chronic hepatitis as the main or sole criterion for
      diagnosing recurrent AIH. However, this also lacks diagnostic specificity because
      there are many other possible causes of chronic hepatitis in the liver allograft.
      In addition, approximately 20% to 40% of biopsies performed on patients as part
      of routine annual review have histological features of chronic hepatitis, for
      which no definite cause can be identified. Risk factors that have been associated
      with the development of recurrent AIH include suboptimal immunosuppression, HLA
      phenotype, disease type and severity in the native liver, and duration of follow
      up. In many cases in which recurrent AIH seems to be related to
      underimmunosuppression, biochemical and histological features rapidly resolve
      once adequate immunosuppression is restored. However, in other cases, recurrent
      AIH behaves more aggressively, with progression to cirrhosis and graft failure.
      Areas that require further study include developing uniform criteria for the
      diagnosis of recurrent AIH, identifying risk factors for severe recurrent
      disease, and determining optimal levels of immunosuppression that minimize the
      impact of disease recurrence without exposing patients to the risks of
      overimmunosuppression.

PMID- 11303287
TI  - Ischemic preconditioning of rat livers against cold storage-reperfusion injury:
      role of nonparenchymal cells and the phenomenon of heterologous preconditioning.
AB  - Brief periods of ischemia followed by reperfusion render tissues resistant
      against subsequent prolonged ischemia, a phenomenon called ischemic
      preconditioning. The effect of ischemic preconditioning on liver transplantation
      was investigated in relation to sinusoidal endothelial cell injury and Kupffer
      cell activation, which are prominent features of storage and reperfusion injury
      leading to liver graft failure. Rat livers were preconditioned by 5 or 10 minutes
      of ischemia and 5 minutes of reperfusion and stored in University of Wisconsin
      (UW) solution for 30 hours. Livers were then reperfused for 15 minutes with
      physiological buffer containing trypan blue. Under these conditions, injury
      occurs predominantly to sinusoidal endothelial cells, reflected by trypan blue
      staining of nonparenchymal cells in histological sections. Ischemic
      preconditioning decreased nonparenchymal cell killing by more than 50%. When half
      the liver was preconditioned, sinusoidal endothelial cells were also protected in
      the contralateral half. Other stored livers were reperfused with nitroblue
      tetrazolium, which is converted to insoluble formazan by superoxide radicals.
      Ischemic preconditioning decreased the intensity of formazan deposition over
      Kupffer cells. Finally, stored livers were transplanted into nontreated rats.
      Ischemic preconditioning improved recipient long-term survival after 30 hours of
      cold ischemic storage in UW solution from 30% to 80% and decreased serum tumor
      necrosis factor-alpha levels in posthepatic blood 4 hours postoperatively from 98
      to 54 pg/mL. In conclusion, ischemic preconditioning protects sinusoidal
      endothelial cells and suppresses Kupffer-cell activation after storage and
      reperfusion. As a result, graft survival improves after liver transplantation.
      Moreover, ischemia to half the liver confers protection to the other half. Such
      heterologous preconditioning provides a new means to protect liver tissue against
      ischemia-reperfusion injury without imposing ischemia on the target tissue.

PMID- 11303288
TI  - Ischemic preconditioning: application in clinical liver transplantation.

PMID- 11303289
TI  - Recurrent autoimmune hepatitis after orthotopic liver transplantation.
AB  - To determine the frequency, risk factors, and consequences of recurrent
      autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease
      were monitored after surgery in accordance with a surveillance protocol.
      Tacrolimus or cyclosporine plus prednisone were administered to each patient, and
      liver biopsy examinations were performed at least annually according to protocol.
      Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent
      disease was defined as the presence of lymphoplasmacytic infiltrates in liver
      tissue in the absence of other causes of allograft dysfunction. Autoimmune
      hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6
      +/- 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by
      surveillance liver biopsy assessment in 2 patients. Histological changes were
      mild, and there was no progression to cirrhosis during 4.9 +/- 0.9 years of
      observation. Five-year patient (86% v. 82%; P =.9) and graft (86% v. 67%; P =.5)
      survival rates were not statistically different between patients with and without
      recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with
      than without recurrence (100% v. 40%; P =.008) and healthy subjects (100% v. 49%;
      P =.01). Recurrent disease was unrelated to donor HLA status. In conclusion,
      recurrence after transplantation for type 1 autoimmune hepatitis is common. Its
      mild manifestations and favorable prognosis may reflect early detection by a
      surveillance protocol and/or continuous corticosteroid treatment. HLA-DR3- or HLA
      DR4-positive recipients are at risk for recurrence regardless of donor HLA
      status.

PMID- 11303290
TI  - Immune response to influenza vaccine in adult liver transplant recipients.
AB  - Influenza virus infection may cause significant complications in liver transplant
      recipients, and whether vaccination is effective in these patients is
      controversial. We performed a study to assess the immune response to influenza
      vaccine in liver transplant recipients and patients with cirrhosis compared with
      healthy controls. Liver transplant recipients (n = 20), patients with compensated
      cirrhosis awaiting transplantation (n = 14), and healthy volunteers (n = 9) were
      administered the standard dose of the 1999 to 2000 inactivated trivalent vaccine
      (A/Bejing/262/95[H1N1]; A/Sidney/5/97[H3N2]; B/Yamanashi/166/98). Antibody
      responses to each component of the vaccine were measured at baseline and after 6
      weeks by hemagglutination inhibition. Vaccination was well tolerated, and no
      major side effects were observed. A significant postvaccination increase in
      antibody titer to all 3 vaccine components was obtained in all groups. However,
      liver transplant recipients had significantly lower postvaccination geometric
      mean titers and geometric mean increases to the H3N2 component compared with
      patients with cirrhosis and controls. The rate of seroconversion to H3N2 after
      vaccination was also significantly lower in liver transplant recipients (15% v.
      89%). We conclude that liver transplant recipients have a significantly impaired
      immune response to the influenza vaccine, and some patients may remain
      unprotected from influenza infection after vaccination. Further studies of
      modified protocols of influenza vaccination for these patients are recommended.

PMID- 11303291
TI  - Double-dose accelerated hepatitis B vaccine in patients with end-stage liver
      disease.
AB  - The aims of this study are to assess the efficacy of hepatitis B virus (HBV)
      vaccination using an accelerated schedule and double dose of recombinant vaccine
      in liver transplant recipients and identify factors associated with
      seroconversion and persistence of antibody to hepatitis B surface antigen (anti
      HBs). Three hundred fifty-six patients were enrolled. Exclusion criteria were
      previous HBV infection, fulminant liver failure, or less than 2 years of follow
      up after orthotopic liver transplantation (OLT). The vaccination schedule was 0,
      2 weeks, 4 weeks, and 6 months using double-dose recombinant vaccine.
      Seroconversion was evaluated prospectively by measuring anti-HBs on the day of
      OLT and 1 and 2 years after OLT. Quantitative analyses of anti-HBs were performed
      retrospectively on stored sera. Geometric mean concentrations (GMCs) were
      calculated using a standard formula. All patients completed the full vaccination
      schedule, and 129 patients (36%) completed the schedule before OLT. The overall
      prevalence of anti-HBs was 128 of 356 pre-OLT samples (36%) compared with 41 of
      353 (11.6%) and 26 of 325 post-OLT samples (8%) 1 and 2 years after OLT,
      respectively (both P =.001). The pre-OLT GMC was 86.7 compared with 0.32 and 0.33
      at 1 and 2 years after OLT, respectively (P =.001). Patients with high titers of
      anti-HBs before OLT were more likely to have persistence of antibodies 1 or 2
      years after OLT. Younger age (P =.02), low Child-Pugh score (P =.02), underlying
      chronic hepatitis C (P=.03), and specific host HLA subtypes were most strongly
      associated with seroconversion and/or persistence of anti-HBs. Thus, (1)
      seroconversion before or after OLT using double-dose accelerated-schedule
      vaccination against HBV is low, (2) there is a rapid, significant decrease in
      antibody titer after OLT, (3) pre-OLT anti-HBs titer potentially may be useful in
      predicting persistence of protective antibodies after OLT, and (4) several
      factors (age, genetic predisposition, severity of liver disease, and underlying
      liver disease) may have a role in poor vaccine responsiveness.

PMID- 11303292
TI  - Modulation of steady-state messenger RNA levels in the regenerating rat liver
      with bile acid feeding.
AB  - Liver regeneration after two thirds partial hepatectomy (PH) is an orchestrated
      hyperplastic growth process requiring coordinated expression of many genes. The
      synchronous progression of 95% of the remnant hepatocytes through the cell cycle
      provides an in vivo model for examining the influence of bile acids on the
      molecular regulation of hepatocyte replication and growth. In this study, we
      examined the effects of endogenous deoxycholic acid (DCA) and ursodeoxycholic
      acid (UDCA) on messenger RNA (mRNA) expression and growth rate during liver
      regeneration. Rats were fed diets containing no addition, 0.4% DCA, UDCA, or both
      for 14 days; they then underwent 70% PH and were maintained on the diets for an
      additional 14 days. mRNA transcript levels for a variety of cell cycle-regulated
      genes were examined post-PH by Northern blot analysis. Bile acid concentrations
      were determined in liver, isolated nuclei, and plasma by gas chromatography and
      mass spectrometry. The results indicated that the addition of DCA and UDCA to the
      diet markedly shifted the bile-acid compositions of liver and plasma. In
      addition, DCA dramatically altered the abundance of many transcripts post-PH,
      whereas coadministration of UDCA suppressed the effect. DCA feeding significantly
      inhibited liver growth through day 3; however, by day 8, it induced an
      approximately 20% increase in mass compared with controls, UDCA-fed, or
      combination-fed animals. UDCA was concentrated greater than 20-fold in nuclei
      compared with whole liver in controls and DCA-fed animals and greater than 2-fold
      with UDCA feeding. These data suggest that bile acids may have a key role in
      liver regeneration, which is significantly altered by modulation of the bile-acid
      pool.

PMID- 11303293
TI  - Adult living donor liver transplantation: Preferences about donation outside the
      medical community.
AB  - An increasing number of transplant centers are performing adult living donor
      liver transplantation (LDLT). We evaluated peoples' perspectives on possible
      outcomes of living donation, thresholds for donating, and views regarding the
      donation process. One hundred fifty people were surveyed; half were from a
      medical care group serving an indigent population and half were from a private
      clinic. Preferences about outcomes of adult living donation were ranked and
      quantified on a visual analogue scale. Thresholds for donation to a loved one
      were quantified. Sixty percent of the respondents suggested they would prefer to
      donate and die and have the transplant recipient live rather than forego donation
      and have the potential transplant recipient die of liver failure. Participants'
      stated threshold for living donation was a median survival for themselves of only
      79%. They would require that their loved one have a median survival of 55% with
      transplantation before they would agree to donate. Respondents from the medical
      care group reported higher survival thresholds for themselves and the transplant
      recipient, and race was the most statistically significant predictor of those
      thresholds. Sex was more predictive of threshold probabilities from the private
      clinic. Eighty-one percent of the respondents believed that the potential donor,
      not a physician, should have the final say regarding candidacy for living
      donation. In conclusion, the findings of this survey support the use of adult
      LDLT. Most respondents were willing to accept mortality rates that far exceed the
      estimated risk of donation and favored outcomes in which a loved one was saved.

PMID- 11303294
TI  - Adult living donor liver transplantation: preferences about donation outside the
      medical community.

PMID- 11303295
TI  - Liver transplantation using sirolimus and minimal corticosteroids (3-day taper).
AB  - At our center, we have performed liver transplantation since 1995 with a rapid
      taper steroid protocol (weaning steroids by day 14 posttransplantation).
      Beginning in 2000, we further reduced the use of corticosteroids to 3 days and
      added sirolimus to our immunosuppressive regimen. We report our experience with
      39 patients who underwent liver transplantation with either tacrolimus or
      cyclosporin A (Neoral; Novartis Pharmaceuticals Corp., Summit, NJ) and sirolimus,
      with a 3-day tapered dose of corticosteroids. Thirty-two patients received a
      cadaveric graft and 7 patients received a right hepatic lobe from a living donor.
      All patients initially were administered either tacrolimus (0.1 mg/kg/d) or
      cyclosporin A (10 mg/kg/d) and sirolimus (6 mg/d for 1 day, followed by 2 mg/d),
      in addition to methylprednisolone on the first 3 days (1, 0.5, and 0.5 g/d) after
      transplantation. Patients were administered corticosteroids for presumptive or
      biopsy-proven evidence of acute cellular rejection (methylprednisolone, 1, 0.5,
      and 0.5 g on 3 successive days). Seventeen patients were administered tacrolimus
      and 22 patients were administered cyclosporin A. Six patients were excluded from
      analysis because they were administered sirolimus for less than 2 weeks. Mean
      duration of follow-up was 124 days. Patient survival was 36 of 39 patients (92%),
      and graft survival was 35 of 39 grafts (89%). Ten of 33 patients (30%)
      experienced 12 episodes of rejection (7 biopsy proven, 5 presumptive) compared
      with 70% in historical controls (P <.01). OKT3 was required in 1 of 33 patients
      (3%) compared with 37% in controls (P <.01). Twenty-six of 33 patients (79%) were
      not administered prednisone, and 7 of 33 patients (21%) were administered
      prednisone for reasons other than rejection. Posttransplantation, there was no
      significant change in values for creatinine, glucose, aspartate aminotransferase,
      bilirubin, cholesterol, and white blood cell counts. Platelet counts were
      significantly reduced, and hematocrits were significantly elevated (P <.05).
      Liver transplantation may be successfully performed with minimal use of
      corticosteroids by using sirolimus and either tacrolimus or cyclosporin A.
      Despite the absence of prednisone from our immunosuppressive protocol, the
      incidence of rejection and OKT3 use was lower than in historical controls.
      Patient and graft survival rates were identical to those of historical controls.
      The findings in this report will serve as the basis for a formal trial evaluating
      the efficacy of sirolimus in liver transplantation.

PMID- 11303296
TI  - Transcranial Doppler sonography and internal jugular bulb saturation during
      hyperventilation in patients with fulminant hepatic failure.
AB  - Mechanical hyperventilation is often used to postpone or ameliorate intracranial
      hypertension in patients with fulminant hepatic failure (FHF). Because such
      treatment may critically reduce cerebral blood flow (CBF), bedside techniques to
      monitor CBF are warranted. In this study, we evaluated the efficacy of
      transcranial Doppler (TCD) sonography of the middle cerebral artery (MCA) and
      internal jugular bulb saturation (svJO(2)) to determine relative changes in CBF
      during mechanical hyperventilation in 8 patients with FHF (median age, 40 years;
      range, 20 to 54 years). We found that TCD and svJO(2) decreased during
      hyperventilation in parallel with CBF, determined by the xenon 133 ((133)Xe)
      washout technique. Quantitatively, the TCD method was less accurate to determine
      carbon dioxide (CO(2)) reactivity compared with svJO(2) and the (133)Xe
      technique. This indicates a slight change in MCA diameter during
      hyperventilation. We conclude that TCD and svJO(2) monitoring may give valuable
      information on relative changes in CBF during hyperventilation. However, the TCD
      method appears less accurate for quantitative estimation of CO(2) reactivity in
      patients with FHF.

PMID- 11303297
TI  - Morbidity and mortality associated with large-bore percutaneous venovenous bypass
      cannulation for 312 orthotopic liver transplantations.
AB  - The aim of this study is to establish the incidence of serious morbidity and
      mortality associated with the placement of large-bore (18 to 20 F) percutaneous
      bypass cannulae for venovenous bypass (VVBP) during orthotopic liver
      transplantation (OLT). This technique has been reported to be rapid, simple, and
      safe. We reviewed the case notes of 312 patients who underwent OLT in our center
      using this technique. We describe 4 cases of serious morbidity (incidence, 1.28%)
      and 1 death (incidence, 0.32%) related directly to percutaneous placement of the
      bypass cannula. We conclude that percutaneous cannula placement for VVBP during
      OLT has the potential for life-threatening complications, and this must be
      considered when electing to use this technique. When percutaneous cannulae are to
      be used, we recommend the use of the right internal jugular vein for return
      cannulation and the use of ultrasound guidance, particularly in those patients in
      whom cannulation is predictably difficult.

PMID- 11303298
TI  - Development of nonalcoholic fatty liver disease after orthotopic liver
      transplantation for cryptogenic cirrhosis.
AB  - Many subjects with cryptogenic cirrhosis have underlying nonalcoholic
      steatohepatitis (NASH). The natural history of NASH-related cryptogenic cirrhosis
      after orthotopic liver transplantation (OLT) is not well defined. A primarily
      retrospective study of patients with the clinical histological phenotype of NASH
      related cirrhosis undergoing OLT was performed. Data were compared with 2 sets of
      age- and weight-matched controls with (1) primary biliary cirrhosis or primary
      sclerosing cholangitis or (2) alcoholic liver disease. After OLT, all patients
      were managed by a standard immunosuppressive protocol. Liver biopsies were
      performed at 6 and 12 months after OLT and at 1- to 2-year intervals thereafter,
      as well as when liver enzyme levels were elevated enough to warrant diagnostic
      biopsy. Twenty-seven subjects with cryptogenic cirrhosis and a clinical
      histological phenotype of NASH and 3 patients with a long-standing diagnosis of
      NASH before OLT were included. The 30-day perioperative mortality was 1 in 30
      patients. During a median follow-up of 3.5 +/- 2.7 years, 2 additional patients
      died of sepsis. There was a time-dependent increase in the risk for allograft
      steatosis that approached 100% by 5 years compared with only an approximately 25%
      incidence of steatosis in the control groups (P <.009, log-rank test). On
      multivariate analysis, only the cumulative steroid dose correlated with time to
      development of allograft steatosis. Three patients developed histological
      progression from hepatic steatosis to steatohepatitis. Of these, 1 patient
      developed progressive fibrosis. Four patients experienced at least 1 episode of
      acute cellular rejection; however, no patient developed chronic rejection or
      graft failure. In conclusion, nonalcoholic fatty liver disease occurs frequently
      after OLT in patients with the phenotype of NASH-related cirrhosis. Despite the
      frequent histological recurrence of disease, clinical outcomes are similar to
      those of other groups of patients undergoing OLT.

PMID- 11303299
TI  - Cholangiographic findings in bile duct ischemia after liver transplantation.

PMID- 11303300
TI  - Living related liver transplantation in biliary atresia with absent inferior vena
      cava.
AB  - The success of the triangulation technique for hepatic venous anastomosis in left
      lateral segment liver transplantation has led to standardization of this
      procedure. We report a case of syndromic biliary atresia with absent inferior
      vena cava in which we constructed a neo cava to implant a living related left
      lateral segment graft by using the triangulation technique.

PMID- 11303301
TI  - Establishing a systematic endoscopic approach to the management of anastomotic
      biliary strictures is needed.

PMID- 11303302
TI  - Cholangioscopy to screen for cholangiocarcinoma in primary sclerosing
      cholangitis.

PMID- 11303303
TI  - Treatment of Behcet's disease--an update.
AB  - OBJECTIVES: To report the experience of the investigators and review the major
      treatment trials conducted for Behcet's disease (BD). METHODS: A MEDLINE
      literature review from 1970 to date was performed on the drugs prescribed for the
      treatment of BD. Open and controlled clinical studies and indications for the
      treatment of affected organs are analyzed. RESULTS: Glucocorticoids are indicated
      for the treatment of BD, although no controlled studies have been reported. The
      combination of corticosteroids and immunosuppressant drugs is used when vital
      organs are involved. Nonsteroidal anti-inflammatory drugs are of little value in
      arthritis. In controlled trials, colchicine was efficacious for erythema nodosum
      and arthritis, particularly in women. Cyclosporine A has a rapid action and when
      combined with azathioprine is effective in patients with severe uveitis and
      extraocular manifestations. Chlorambucil is indicated for uveitis and
      meningoencephalitis. In controlled studies, azathioprine prevented unilateral
      uveitis from becoming bilateral and improved extraocular symptoms. Pulse
      cyclophosphamide combined with corticosteroids improves severe systemic
      vasculitis. Interferon alpha benefits ocular and extraocular manifestations, but
      controlled studies are lacking. Methotrexate is indicated for uveitis and
      arthritis, and sulfasalazine improves gastrointestinal vasculitis. In controlled
      trials, thalidomide was effective for mucocutaneous manifestations, but on its
      discontinuation the disease exacerbated. Orogenital manifestations are treated
      with local application of corticosteroids or other medications. CONCLUSIONS:
      Combination therapy is not always efficacious in controlling inflammation. The
      goal of management is to treat early to avoid recurrences and irreversible damage
      to the vital organs. With proper management of BD, loss of useful vision was
      reduced from 75% to 20% of the affected eyes. However, less favorable results are
      seen for central nervous system and large artery and vein involvement.

PMID- 11303304
TI  - Anti-nuclear envelope antibodies: Clinical associations.
AB  - OBJECTIVES: Characterization of the clinical associations and clinical
      implications of antibodies reacting with antigens of the nuclear envelope.
      METHODS: Description of an illustrative case and a MEDLINE search-assisted
      literature review of relevant cases. RESULTS: With indirect immunofluorescence,
      autoantibodies directed against various antigens of the nuclear envelope stain
      the nucleus in a ring-like (rim) pattern. Autoantibodies against 5 antigenic
      components of the nuclear envelope have been described: anti-gp210, p62, lamina,
      lamina-associated polypeptides, and lamin B receptor. Antibodies to antigens of
      the nuclear pore complex, such as gp210 and p62, are highly specific (> 95%) for
      primary biliary cirrhosis and may aid in the serologic diagnosis of this
      condition, especially in cases in which antimitochondrial antibodies are not
      detectable. In contrast, antilamin antibodies are not disease-specific but seem
      to be associated with lupus anticoagulant or anticardiolipin antibodies,
      antiphospholipid syndrome, thrombocytopenia, autoimmune liver diseases, and
      arthralgia. High-titered antilamin antibodies help to define a subset of lupus
      patients with antiphospholipid antibodies who are at a lower risk of developing
      thrombotic events. In addition, preliminary data suggest that the presence of
      antilamin antibodies may be helpful in the diagnosis of chronic fatigue syndrome.
      CONCLUSIONS: Each of the antibodies reacting with nuclear membrane antigens has
      its own spectrum of disease associations. RELEVANCE: Determination of anti
      nuclear envelope antibody pattern by indirect immunofluorescence, with subsequent
      determination of the specific antibody, carries important diagnostic and
      prognostic implications in various autoimmune conditions.

PMID- 11303305
TI  - Clinical, radiologic, demographic, and occupational aspects of hand
      osteoarthritis in the elderly.
AB  - OBJECTIVE: Osteoarthritis (OA) of the hand is common in elderly patients. The aim
      of this study was to characterize OA frequency, severity, and distribution and to
      trace interrelationships between these findings and the demographic,
      occupational, and medical data from elderly Jewish nonrheumatologic patients.
      METHODS: Study participants were 253 consecutive patients admitted to a geriatric
      center for a variety of nonrheumatic medical conditions. Excluded patients were
      those with rheumatoid arthritis; neurologic, orthopedic, or other conditions that
      would interfere with symmetric hand function; and mental or medical states that
      would interfere with history taking and radiographic studies. Patient occupations
      were graded as workload degree (on a scale of 1 to 3) and as the total
      occupational score (workload degree multiplied by the duration of each job).
      Clinical findings of Heberden nodes, Bouchard nodes, and malignment, graded on a
      scale of 0 to 3, were summed as the clinical OA score. Hand radiographs were
      independently read (modified Altman method), grading 5 parameters in each joint
      on a scale of 0 to 3, summed as a radiologic OA score. Statistical analyses
      included the Student t test, chi(2) test, ANOVA, Pearson correlation, and partial
      correlation coefficients. RESULTS: Among 253 elderly patients (171 women, 82 men;
      mean age, 79 years) OA was frequent (occurring in about 80% of patients),
      involving most severely the second and third distal interphalangeal, right first
      interphalangeal, and both first carpometacarpal joints. The prevalence of OA was
      similar in women and men, with higher scores in women, and reached significance
      only in the distal interphalangeal joints. Metacarpophalangeal joints were more
      involved in men. Age had a clear influence on OA scores. Ethnicity affected OA
      severity, with Ashkenazi Jews having significantly higher scores than Sepharadi
      Jews. Dominant hands had significantly higher global OA scores as well as
      isolated joint scores (except for the first carpometacarpal joint). Occupational
      load, housekeeping tasks, and the number of children did not influence the total
      or specific joint OA scores. Associated conditions such as obesity, diabetes,
      hypothyroidism, and chondro calcinosis were not associated with more pronounced
      OA. CONCLUSIONS: Hand OA was prevalent in our elderly cohort, and its severity
      was influenced by inherent traits such as age, female gender, ethnicity, and
      handedness. In contrast, acquired factors such as workload, number of children,
      and associated diseases did not appear to influence OA expression.

PMID- 11303306
TI  - Systemic sclerosis in 3 US ethnic groups: a comparison of clinical,
      sociodemographic, serologic, and immunogenetic determinants.
AB  - OBJECTIVE: To determine whether ethnic factors influence the presentation,
      serologic expression and immunogenetics of systemic sclerosis (SSc), patients
      from 3 ethnic groups were compared for clinical features, SSc-associated
      autoantibodies, and human leukocyte antigen (HLA) class II alleles. METHODS:
      Fifty-four Hispanics, 28 African Americans, and 79 whites from Texas with recent
      onset (less than 5 years) SSc enrolled in a prospective longitudinal study were
      assessed for sociodemographic, clinical, immunologic, immunogenetic, behavioral,
      and psychologic parameters using validated instruments and standard laboratory
      techniques. Serologic and immunogenetic characteristics from these patients and
      larger retrospective SSc cohorts of the same ethnic groups also were examined.
      RESULTS: Hispanics and African Americans in the prospective cohort were more
      likely to have diffuse skin involvement, skin pigmentary changes, digital ulcers,
      pulmonary hypertension (African Americans), and an overall lower sociodemographic
      status than whites, who had more facial telangiectasia and hypothyroidism. In the
      larger combined prospective and retrospective groups of SSc patients, whites were
      likely to have more anticentromere antibodies (ACA) and African Americans more
      anti-U1-ribonucleoprotein (RNP) and anti-U3-RNP (fibrillarin) autoantibodies. HLA
      DQB1*0301 was significantly associated with SSc per se in all 3 ethnic groups;
      HLA-DRB1*11 correlated with the anti-topoisomerase I antibody response, and HLA
      DRB1*01, DRB1*04, and DQB1*0501 with ACA. CONCLUSIONS: Important
      sociodemographic, clinical, and serologic differences exist between whites,
      African Americans, and Hispanics, despite shared genetic (HLA class II)
      predisposing factors. The impact of these differences on prognosis remain to be
      determined.

PMID- 11303307
TI  - Sonographically guided procedures in rheumatology.
AB  - OBJECTIVE: To provide some representative examples of sonographically guided
      arthrocentesis and intralesional injection therapy. METHODS: Sonographic
      evaluation was performed with high-frequency linear (13 MHz) and mechanical
      sector (20 MHz) transducers. The images were obtained in representative patients
      with rheumatoid arthritis and posttraumatic subacromial bursitis. RESULTS:
      Sonographically guided intralesional injection is a rapid and reliable procedure,
      especially in patients with arthritis, tenosynovitis, and bursitis. After target
      localization, needle placement can be performed under continuous sonographic
      monitoring. Sonographic guidance is particularly useful when fluid collections
      are small (less than 5 mm) and deep or when the inflammatory process is adjacent
      to anatomic structures that could be seriously damaged by the injection.
      CONCLUSIONS: Over the last few years, the rapid technologic advancements in
      ultrasonography have dramatically increased the potential applications of
      sonographically guided procedures. The simplicity and reliability of the
      technique might warrant rheumatologists to undergo sonographic training.

PMID- 11303308
TI  - The nosology-taxonomy of recent-onset arthritis: the experience of early
      arthritis clinics.
AB  - OBJECTIVE: To compare the conclusions of studies addressing the outcome of early
      arthritis cohorts. METHODS: The methodologies of previous reports on early
      arthritis cohorts were examined, and their results and conclusions were compared.
      RESULTS: Thirty-four reports on 23 cohorts of early arthritis were found. The
      methodology was poor in most studies, with numerous inclusion and exclusion
      biases, frequently short follow-up periods, and a lack of precision about the
      rationale for diagnosis. However, similar conclusions were reached on several
      points: a large number of cases of early arthritis remained undifferentiated
      and/or resolved spontaneously, about 80% of cases initially classified as
      undifferentiated or rheumatoid arthritis retained this diagnosis during follow
      up, and the incidence of psoriatic arthritis in most studies was similar (2% to
      4%). Conversely, there were striking discrepancies among studies concerning the
      frequency of crystal arthropathies (0% to 18%), spondyloarthropathy (1% to 33%)
      and rheumatoid arthritis (15% to 47%). CONCLUSIONS: There appears to be a lack of
      agreement among researchers about the nosology and/or taxonomy of many cases of
      mild arthritis, despite the existence of classification criteria. RELEVANCE:
      Recognition of cultural bias in the diagnosis of early arthritis could be a
      prerequisite for the optimization of new sets of criteria for the diagnosis of
      early rheumatoid arthritis and spondyloarthropathy.

PMID- 11303309
TI  - Cryoglobulinemia in systemic lupus erythematosus: prevalence and clinical
      characteristics in a series of 122 patients.
AB  - OBJECTIVES: To determine the prevalence and nature of cryoglobulins in 122
      patients with systemic lupus erythematosus (SLE) and identify the clinical and
      immunologic features related to their presence. METHODS: In a cross-sectional
      study, we investigated 122 consecutive patients (106 women and 16 men) with SLE
      who fulfilled the 1982 revised criteria of the American College of Rheumatology
      for the classification of SLE. All patients had documented medical histories and
      underwent a medical interview as well as a routine general physical examination
      by a qualified internist, and their clinical and serologic characteristics were
      collected on a protocol form. Serum samples were obtained at 37 degrees C, and
      cryoglobulinemia was estimated by centrifugation at 4 degrees C after incubation
      for 7 days in all patients. The type of cryoglobulinemia was identified by
      agarose gel electrophoresis and immunofixation. RESULTS: Cryoglobulins were
      detected in the sera of 31 SLE patients (25%): 20 patients (65%) had a cryocrit
      lower than 1%, 8 (26%) had percentages ranging between 1% and 5%, and only 3
      patients (9%) had a cryocrit over 5%. Only cutaneous vasculitis (39% v 16%; P =
      .01) was more prevalent in patients with than in those without cryoglobulins.
      Rheumatoid factor (RF) (42% v 15%; P = .002) and low CH50 levels (84% v 49%; P
      <.001) were more prevalent in SLE patients with cryoglobulins. Hepatitis C virus
      (HCV) infection was investigated in 24 of the 31 cryoglobulinemic SLE patients
      and was detected in 5 (21%). In comparison, 4 (5%) of the 75 noncryoglobulinemic
      SLE patients studied were positive (P = 0.035; odds ratio, 4.67). Patients with a
      cryocrit greater than 1% showed a higher frequency of HCV infection than those
      with a cryocrit less than or equal to 1% (46% v 0%, P = .01). CONCLUSIONS:
      Cutaneous vasculitis, RF, hypocomplementemia, and HCV infection were associated
      with cryoglobulins in SLE patients. Testing for HCV infection is therefore
      recommended for patients with SLE and cryoglobulinemia to identify this subset of
      patients for prognostic and therapeutic reasons.

PMID- 11303310
TI  - [Activity of transmembrane calcium transport and levels of endothelin-1 in
      patients with variant angina].
AB  - Recent studies showed that coronary artery spasm may be due to disturbances of
      secretory and excretory endothelial activity in atherosclerotic coronary artery.
      However, this theory does not explain the reasons of coronary artery spasm when
      endothelium is not damaged. There must be other patomechanisms of coronary artery
      spasm. The aim of our study was examination of calcium efflux through the
      lymphocytic cell membrane and determination of endothelin-1 plasma levels in
      patients with variant angina in order to define the participation of these
      factors in pathogenesis of coronary artery spasm. The survey was made in 76
      patients with ischaemic heart disease. All patients were divided into 2 groups.
      The first group consisted of 48 patients with variant angina (d.b.s.), the other
      consisted of 28 patients with stable angina (d.b.w.). The control group (g.k.)
      was composed of 25 healthy people. Patients were administered 100 ml of
      trometamol (TRIS, pH = 10.5) intravenously for 5 minutes. After stopping the
      infusion the examined patient was breathing deeply for 5 minutes at a rate of
      40/min. The endothelin-1 (ET-1) plasma levels and transmembrane calcium transport
      in lymphocytes were determined before and just after the hyperventilation test,
      as well as 10 minutes after the test. ET-1 plasma concentrations were estimated
      with a radioimmunologic assay. The method of estimation of transmembrane calcium
      transport was elaborated in Laboratory of Department of Cardiology of Medical
      University of Wroclaw. We showed that ET-1 plasma levels and transmembrane
      calcium transport in patients with d.b.s. before the test were normal. There was
      an increase in transmembrane calcium efflux in patients with d.b.s. during
      coronary artery spasm that had been caused by ET-1. ET-1 plasma levels were still
      high 10 min. after the coronary artery spasm. Disturbances of transmembrane
      calcium transport and increased endothelin-1 plasma level may be the primary
      factors responsible for coronary artery spasm.

PMID- 11303311
TI  - [Bone tissue metabolism in patients with rheumatoid arthritis treated with
      glucocorticosteroids].
AB  - The present study has been undertaken to evaluate bone turn-over in rheumatoid
      arthritis (RA) patients as well as the influence of low dose glucocorticosteroids
      (gcs) on bone mass loss. Ninety patients with establish RA has been investigated.
      The patients have been divided into two groups: 44 patients treated with gcs (age
      52.5 +/- 12.4 years, disease duration 122 +/- 102 months, total dose of GCS,
      equivalent to prednisone -7.4 +/- 8.3 g) and 46 patients who were not treated
      with gcs (age 54.3 +/- 9.7 years, disease duration 134 +/- 120 month). Fifty
      patients have been assessed twice (after 12 month). Bone mineral content and bone
      mineral density have been determined in all patients in distal forearm.
      Additionally, some biochemical markers of osteoporosis: osteocalcin, alkaline
      phosphatase-bone formation, carboxyterminal telopeptides of type I collagen
      (CTx), procollagen type I carboxyterminal propeptide (PICP), deoxypyridynoline
      and some proinflammatory cytokine: IL-1 alpha, IL-6, TNF-alpha, GM-CSF has been
      determined. No difference in bone metabolism between RA patients receiving gcs
      treatment and those treated without gcs was shown. It is concluded that anti
      inflammatory effect of gcs may balance the direct effect of gcs on bone mineral
      content in RA patients, particularly those with short term treatment.

PMID- 11303312
TI  - [The concentration of adenine nucleotides in platelets of patients with primary
      chronic glomerulonephritis].
AB  - Nephrotic syndrome (n.s.) is associated with numerous blood coagulation
      abnormalities and a marked predisposition to thromboembolism. Increased
      aggregation and activation of platelets in patients with glomerulonephritis
      (g.l.n. p.t.s.) may partly explain this status. The aim of this study was to
      measure the platelets adenine nucleotides concentration. The study was performed
      in 57 patients with a renal biopsy confirmed primary glomerulonephritis and 24
      sex and age matched healthy volunteers which served as a control group. The
      patients were divided into two subgroups: subgroup I/A--36 patients with the
      symptoms of the nephrotic syndrome and subgroup I/B--21 patients with chronic
      glomerulonephritis and proteinuria but without the symptoms of nephrotic
      syndrome. Concentration of adenine nucleotides in platelets was measured using
      HPLC. In the subgroup I/A significantly lower levels of ATP, ADP and AMP
      concentrations in platelets were observed comparing to control subjects.
      Simultaneously significant correlation between both ATP and ADP concentration and
      plasma levels of albumin, total cholesterol, LDL-cholesterol, triglycerides and
      fibrinogen were found in g.l.n. p.t.s. SUMMARY AND CONCLUSIONS: 1. Significantly
      lower concentrations of adenine nucleotides in platelets of gln pts with the
      nephrotic syndrome may result from their activation. 2. Protein and lipid
      metabolism as well as fibrinogen seem to influence ATP and ADP concentrations in
      platelets of g.l.n. p.t.s.

PMID- 11303313
TI  - [Viscosity of blood and plasma in patients with single- and multi-vascular
      coronary heart disease].
AB  - The aim of this study was to establish a connection between rheological
      disturbances and extensiveness of atherosclerotic changes in coronary angiogram.
      Patients were classified into two groups: group I--with multivascular
      atherosclerotic lesions (45 subjects at age of 58 +/- 11 years), group II--with
      univascular atherosclerotic lesions (18 subjects at age of 55 +/- 9 years). Blood
      samples were drawn from the cubital vein prior to the angiogram. Blood viscosity
      measurements were performed using low-shear Contraves viscometer-100 at 0.116;
      1.0; 4.59 s-1 shear rates and Brokfield Cone/Plate Viscometer at 150 s-1. The
      plasma viscosity was measured by means of Ubbelohde's capilary viscometer.
      Besides the viscometric examinations the total cholesterol. LDL-cholesterol, HDL
      cholesterol, triglycerides, glucose and fibrinogen as well as blood morphology
      and ESR were determined. All rheological measurements were carried out at the
      temperature of 37 degrees C immediately after blood drawing. The results of
      studies indicate that in patients with multivascular coronary disease whole blood
      viscosity at all examined shear rates was significantly greater then in
      univascular patients. It was found that the LDL-lipoproteins concentration was
      significantly elevated in the I group. Other examined parameters did not differ
      significantly. The examinations indicate that there exists the connection between
      hemorheological disturbances and the extensiveness of coronary heart disease.

PMID- 11303314
TI  - [The effect of a single moderate physical exertion on serum leptin levels in
      patients with essential hypertension (preliminary results)].
AB  - Leptin is a product of the ob gene and is secreted by the adipose tissue. It
      takes part in regulation of nervous, cardiovascular, endocrine system and renal
      functions. The aim of this study was to assess the influence of short term
      moderate exercise on serum leptin levels in patients with arterial hypertension.
      The study group consisted of 34 patients with essential hypertension: 15 women
      (48.9 +/- 12.1 years old) and 19 men (43.5 +/- 14.6 years old). There were 7
      patients with stage I of hypertension, 17 patients with stage II of hypertension
      and 10 patients with stage III of hypertension. The blood samples were taken
      before and after the exercise test. Serum leptin levels were assessed by
      radioimmunoassay. Serum leptin levels were significantly higher in women then in
      men. The logarithm of serum leptin levels after the exercise was significantly
      lower than before (0.8 +/- 0.4 and 0.9 +/- 0.5 respectively). The moderate, short
      term exercise decreases serum leptin levels in the hypertensive patients.

PMID- 11303315
TI  - [Clinical evaluation of glimepiride in treatment of type 2 diabetes. Results of a
      multicenter study].
AB  - In a multicenter study 142 patients (from 8 centers) with type 2 diabetes (77 men
      and 65 women, mean age 57 +/- 8.5 (SD) yrs, mean duration of diabetes 64.4 +/-
      57.7 months, mean BMI 28.7 +/- 3.6 kg/m2) received over 3 months as the only
      antidiabetic drug glymepiride (Amaryl) once daily before breakfast in the dose of
      0.5-7.0 mg, but mostly 1-3 mg. The treatment was interrupted in one patient due
      to metabolic deterioration which needed insulin therapy, in an other one because
      of allergic eruption, and in two because of insufficient compliance. In all other
      patients the satisfactory decrease of glyceaemia in fasting state and over the
      day was obtained: the median value of the mean daily glycemia decreased from 8.8
      mmol/l (158 mg/dl) to 7.2 mmol/l (129 mg/dl), p < 0.001, of the mean Mw index
      from 12 to 8.2, p < 0.001, also the median value of HbA1c diminished from 8.0 to
      7.35%, p < 0.001. These effects were particularly evident in a subgroup of 28
      patients with diabetes duration below 1.5 yrs: at the end of the study no one
      blood glucose value in the daily profile did exceed 7.7 mmol/l (140 mg/dl). No
      significant change of BMI, serum triglycerides and serum total cholesterol was
      observed, instead a significant decrease of mean systolic and diastolic blood
      pressure took place (from 143 +/- 20 to 136 +/- 17 mm Hg, p < 0.001, and from 85
      +/- 10 to 83 +/- 9 mm Hg, p < 0.001, respectively). The tolerance of the drug was
      good. The verified hypoglycaemia developed in one patient (0.7%). No changes of
      the laboratory safety parameters were observed.

PMID- 11303316
TI  - [Thrombocytopenia associated with cytomegalovirus infection in an immunocompetent
      patient].
AB  - We present case 46-yers old woman with severe thrombocytopenia during
      cytomegalovirus infection. Administration of corticosteroids has given short-term
      normalizations platelets count. Eventually treatment by Gancyclovir has allowed
      to obtain haematology and virology remission.

PMID- 11303317
TI  - [Coronary disease in women--ongoing problematic diagnostic issues].

PMID- 11303318
TI  - [Polyarteritis nodosa].

PMID- 11303319
TI  - [Hematological paraneoplastic syndromes].

PMID- 11303320
TI  - [Pathophysiology of autosomal dominant polycystic kidney disease].

PMID- 11303322
TI  - [The first Polish-Slovak Conference of Internal Medicine, Ustron-Jaszowiec, May
      26-27, 2000].

PMID- 11303321
TI  - [Clinical view of autosomal dominant polycystic kidney disease].

PMID- 11303323
TI  - [Photoplethysmographic evaluation of microcirculation in patients with overt and
      latent hyperthyroidism or hypothyroidism].
AB  - Alterations in the finger microcirculation in patients with disturbed function of
      the thyroid gland was evaluated with planimetric photoplethysmography. One
      hundred forty-one patients with disturbed thyroid function (31 overt
      hyperthyreoidism, 10 latent hyperthyreoidism, 79 overt hypothyreoidism, 22 latent
      hypothyroidism) and 30 healthy individuals were investigated. Serum free
      thyroxine and thyreotropine level were determined in all investigated subjects.
      The systolic-diastolic index (SDI) was measured in all individuals with
      photopletysmography. A decrease in SDI was found in the patients with
      hyperthyroidism (overt 0.121; latent 0.158) and an inverse in SDI was shown in
      hypothyroid patients (overt 0.617; latent 0.471) was compared with the controls
      (0.345). SDI correlated with serum free thyroxine and thyreotropine levels and
      clinical symptoms.

PMID- 11303324
TI  - [Elevated levels of homocysteine in plasma as a risk factor for coronary artery
      disease].
AB  - This study was performed to assess the significance of association between
      coronary artery disease (CAD) and circulating homocysteine concentrations. 100
      consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for
      PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma
      for homocysteine and vitamins were obtained. The controls were without clinical
      evidence of coronary artery disease and hypertension (90 men and 30 women aged 32
      to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and
      plasma vitamin B12 were assayed by immunofluoroscency (Delphia test).
      Homocysteine concentrations were higher in patients than in controls (13.61 +/-
      4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had
      nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46
      +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level-
      defined as one in the top fifth of the control distribution > or = 12.83 mumol/L-
      was seen in 46% of the patients compared with 20% of the control group (p =
      0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level
      was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5
      mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001,
      adjusted for age). After adjustment for conventional risk factors (age, smoking,
      hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level
      remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We
      observed inverse correlation between homocysteine and folate level (r = -0.32, p
      = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p =
      0.03), especially in men. Patients with elevated homocysteine level had lower
      levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05),
      and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than
      patients with normal level of homocysteine. Elevated plasma homocysteine level is
      a strong risk factor for coronary artery disease. A 5 mumol/L increment in total
      homocysteine level may be associated with twofold increase of risk for the
      disease.

PMID- 11303325
TI  - [Use of platelet function analyzer PFA-100 and whole blood aggregometry to
      monitor blood platelet sensitivity to acetylsalicylic acid (aspirin). Is it
      possible to reliably monitor antiplatelet treatment using routine laboratory
      diagnostic methods?].
AB  - Introduction of the antiplatelet agents of new generations and the occurrence of
      the phenomenon of "aspirin-resistance" triggered the search for better, simpler
      and more reliable routine diagnostic methods to monitor platelet reactivity. Our
      objective was to evaluate the usefulness and reliability of two simple methods:
      platelet function analyzer (PFA-100) and whole blood platelet aggregometry for
      monitoring of platelet function in 18 healthy blood donors and 35 patients with
      ischaemic heart disease (IHD) subjected to small doses/75 mg and 150 mg a day) of
      acetylsalicylic acid (aspirin). In 50% of healthy blood donors the intake of 75
      mg ASA a day resulted in the prolongation of PFA-100 collagen/epinephrine closure
      time (CEPI = (relevant to reduced platelet reactivity) of over 150 s, whereas 75%
      donors responded to 150 mg ASA-. Otherwise, the daily dose of 150 mg ASA resulted
      in a prolonged CEPI merely in 23% of in IHD patients. At both doses ASA
      completely inhibited the arachidonic acid-induced whole blood platelet
      aggregation in all healthy donors and in all but 3 IHD patients. Collagen-induced
      platelet aggregation was only negligibly affected by either dose of ASA. Our
      results point that the simultaneous monitoring of the PFA-100
      collagen/epinephrine closure time and whole blood platelet aggregometry (Chrono
      Log) enables to reliably evaluate the inhibition of platelet function by ASA and
      discriminate the partial or complete platelet insensitivity to aspirin. The
      phenomenon of more frequent platelet aspirin-resistance in IHD patients requires
      to be verified in randomised clinical prospective studies.

PMID- 11303326
TI  - [Polymorphism of the chymase gene and development of retinopathy in type 2
      diabetic patients].
AB  - Diabetic retinopathy is one of the major causes of blindness in developed
      countries. Among the factors involved in development of retinopathy genetic
      factors related to the generation of angiotensin II are mentioned. Recently was
      described that tissue chymase enzyme is the alternative trait for angiotensin II
      formulation. The aim of the study was assessment of association of CMA/B hCC
      polymorphism of chymase gene with the development and progression of diabetic
      retinopathy. The study was conduced in 587 type 2 diabetic patients with diabetes
      duration longer than 10 years. Mean age 62.8 +/- 8.58, mean duration 16.7 +/-
      5.66, HbA1c 8.23 +/- 1.71, BMI 29.1 +/- 4.91. Ophthalmological examination was
      performed to determine the presence of retinopathy. Next polymorphism CMA/B hCC
      chymase gene by PCR method was assessed. Gene distribution was estimated by chi
      square test. In the whole examined group no significant changes of gene
      distribution was found. However, in female group without retinopathy the tendency
      to lower incidence of GG genotype was observed (p = 0.06). When assessed the
      female group without retinopathy despite 15 years duration of diabetes frequency
      decrease of GG genotype was significant (p = 0.04). According to the results we
      conclude that CMA/B hCC chymase gene polymorphism is associated with the presence
      of diabetic retinopathy. Association is expressed by decreased frequency of GG
      genotype in female group without retinopathy.

PMID- 11303327
TI  - [Micronized fenofibrate, decreased triglyceride levels, total cholesterol and LDL
      fractions in serum].
AB  - Elevated serum level of triglycerides is a classic indication for fibrates.
      Micronized fenofibrate is hypolipemic drug with proven safety and efficacy in a
      view of triglycerides reduction, but according to few papers published so far on
      the subject is also effective in decreasing elevated total and LDL cholesterol.
      The aim of study was to confirm results obtained from these few previous studies.
      Forty seven persons with lipid disturbances (25 males and 22 females, age range
      34-71 yrs. mean 48.0) entered the study. Thirty two patients had a history
      myocardial infarction and fifteen persons without clinical symptoms of heart
      diseases. All of them were treated with micronized fenofibrate 200 mg daily.
      Micronized fenofibrate decreased serum concentration of total cholesterol by
      13.4% (p < 0.01), LDL cholesterol by 21.2% (p < 0.001) and triglycerides by 39.5%
      (p < 0.001) in whole group of patients. Most beneficial effects were obtained in
      persons with mixed hyperlipidemia: reduction of total cholesterol, triglycerides
      and LDL cholesterol serum levels was 22.4% (p < 0.01), 52.5% (p < 0.0001), 25.4%
      (p < 0.01), respectively. In individuals with hypercholesterolemia a reduction of
      total cholesterol by 11% (p < 0.05) and LDL cholesterol by 15.4% (p < 0.05) was
      observed. In the group with hypertriglyceridemia or mixed hyperlipidemia
      reduction of serum triglycerides concentration by 33.5% (p < 0.05) was achieved.
      No significant change in serum HDL cholesterol level in any group was observed.
      The treatment with micronized fenofibrate was well tolerated. Our study shows
      that this drug is safe and seems to be effective in some cases with increased
      serum total and LDL cholesterol level as well.

PMID- 11303328
TI  - [The significance of lowered ejection fraction on prognosis after myocardial
      infarction ].
AB  - The subject of this study was a group of 757 patients hospitalized because of
      acute myocardial infarction in years 1992-1996, who survived the in-hospital
      course and were under observation for 2-6 years after the infarction. During the
      14-18th day of the hospital stay they were made an echocardiographic test,
      including the ejection fraction (EF). The aim of this study was to define the
      influence of the ejection fraction value lowered below 40% on the long-term
      prognosis in patients after acute myocardial infarction. We compared two groups
      of patients; group I, consisting of 130 (17.2%) patients with EF lowered below
      40% and group II, which included 627 patients with EF over 40%. To estimate the
      statistic significance we used the chi-square and t-Student test. The morbidity
      curves were made with the Kaplan-Meier method. The course of the myocardial
      infarction was much more grave in group I than in group II, what is confirmed by
      a more often anterior ventricular infarction and the quantity of dangerous
      complications which occurred during the in-hospital phase. The multi-factor
      regressive analysis showed that the ejection fraction lowered below 40% raises
      2.47 times (95% confidence interval 1.50-4.07) (p < 0.001) the risk of death
      during the first year after myocardial infarction and nearly two times during the
      5 year follow-up, compared to patients with a higher EF value. The influence of
      the EF value lowered below 40% on the creation of an infarction was not
      significant. The EF value lowered below 40% in patients after acute myocardial
      infarction was a significant risk factor in the long-term prognosis. More than
      40% of deaths during the long-term prognosis in this group were caused by heart
      failure.

PMID- 11303329
TI  - [A rare case of 75-year survival in a woman with Turner syndrome].
AB  - The authors presents the rare case of survival time of 75-year-old woman with
      Turner syndrome. The skeletal and the circulatory systems changes on the
      radiograms are presented.

PMID- 11303330
TI  - [Pernicious anemia in a patient with chronic alcoholism].
AB  - A case of pernicious anaemia in 43 years old woman with alcoholism is presented.

PMID- 11303331
TI  - [Incidental discovery of an adrenal mass (incidentaloma)--contemporary opinion].

PMID- 11303332
TI  - [St. George's Hospital questionnaire (St. George's Respiratory Questionnaire) as
      an instrument for quality of life assessment in respiratory tract diseases].
AB  - St. George's Respiratory Questionnaire (SGRQ) is one of the main measures of the
      quality of life in patients with pulmonary diseases. We review the literature
      concentrating the use of SGRQ in patients with asthma, chronic obstructive
      pulmonary disease, bronchectases, interstitial lung disease and in adult
      respiratory distress syndrome (ARSD).

PMID- 11303333
TI  - [Graves-Basedow's disease: effect of treatment methods for hyperthyroidism on the
      course of ophthalmopathy].
AB  - Efficient and permanent restoration of euthyreosis is an important factor in the
      therapy of Graves' ophthalmopathy (GO). The choice for a treatment method of
      thyreotoxicosis (thyreostatic drugs, radioiodine, strumectomy) may influence the
      natural course of the coexistent ophthalmopathy. Some forms of therapy seem to
      facilitate the withdrawal of the ophthalmic symptoms, while the others may worsen
      or even increase the risk of the reveal of GO. This paper includes the discussion
      of the influence of a chosen treatment of hyperthyreoidism on the course of GO.

PMID- 11303334
TI  - [Treatment of small cell lung cancer].

PMID- 11303335
TI  - [Chronobiology in medicine].

PMID- 11303336
TI  - [Circadian rhythm of blood pressure in patients with chronic renal failure].

PMID- 11303337
TI  - The neurology of syntax: language use without Broca's area.
AB  - A new view of the functional role of the left anterior cortex in language use is
      proposed. The experimental record indicates that most human linguistic abilities
      are not localized in this region. In particular, most of syntax (long thought to
      be there) is not located in Broca's area and its vicinity (operculum, insula, and
      subjacent white matter). This cerebral region, implicated in Broca's aphasia,
      does have a role in syntactic processing, but a highly specific one: It is the
      neural home to receptive mechanisms involved in the computation of the relation
      between transformationally moved phrasal constituents and their extraction sites
      (in line with the Trace-Deletion Hypothesis). It is also involved in the
      construction of higher parts of the syntactic tree in speech production. By
      contrast, basic combinatorial capacities necessary for language processing--for
      example, structure-building operations, lexical insertion--are not supported by
      the neural tissue of this cerebral region, nor is lexical or combinatorial
      semantics. The dense body of empirical evidence supporting this restrictive view
      comes mainly from several angles on lesion studies of syntax in agrammatic
      Broca's aphasia. Five empirical arguments are presented: experiments in sentence
      comprehension, cross-linguistic considerations (where aphasia findings from
      several language types are pooled and scrutinized comparatively), grammaticality
      and plausibility judgments, real-time processing of complex sentences, and
      rehabilitation. Also discussed are recent results from functional neuroimaging
      and from structured observations on speech production of Broca's aphasics.
      Syntactic abilities are nonetheless distinct from other cognitive skills and are
      represented entirely and exclusively in the left cerebral hemisphere. Although
      more widespread in the left hemisphere than previously thought, they are clearly
      distinct from other human combinatorial and intellectual abilities. The
      neurological record (based on functional imaging, split-brain and right
      hemisphere-damaged patients, as well as patients suffering from a breakdown of
      mathematical skills) indicates that language is a distinct, modularly organized
      neurological entity. Combinatorial aspects of the language faculty reside in the
      human left cerebral hemisphere, but only the transformational component (or
      algorithms that implement it in use) is located in and around Broca's area.

PMID- 11303338
TI  - Niche construction, biological evolution, and cultural change.
AB  - We propose a conceptual model that maps the causal pathways relating biological
      evolution to cultural change. It builds on conventional evolutionary theory by
      placing emphasis on the capacity of organisms to modify sources of natural
      selection in their environment (niche construction) and by broadening the
      evolutionary dynamic to incorporate ontogenetic and cultural processes. In this
      model, phenotypes have a much more active role in evolution than generally
      conceived. This sheds light on hominid evolution, on the evolution of culture,
      and on altruism and cooperation. Culture amplifies the capacity of human beings
      to modify sources of natural selection in their environments to the point where
      that capacity raises some new questions about the processes of human adaptation.

PMID- 11303339
TI  - Behavioral momentum and the law of effect.
AB  - In the metaphor of behavioral momentum, the rate of a free operant in the
      presence of a discriminative stimulus is analogous to the velocity of a moving
      body, and resistance to change measures an aspect of behavior that is analogous
      to its inertial mass. An extension of the metaphor suggests that preference
      measures an analog to the gravitational mass of that body. The independent
      functions relating resistance to change and preference to the conditions of
      reinforcement may be construed as convergent measures of a single construct,
      analogous to physical mass, that represents the effects of a history of exposure
      to the signaled conditions of reinforcement and that unifies the traditionally
      separate notions of the strength of learning and the value of incentives.
      Research guided by the momentum metaphor encompasses the effects of reinforcement
      on response rate, resistance to change, and preference and has implications for
      clinical interventions, drug addiction, and self-control. In addition, its
      principles can be seen as a modern, quantitative version of Thorndike's (1911)
      Law of Effect, providing a new perspective on some of the challenges to his
      postulation of strengthening by reinforcement.

PMID- 11303340
TI  - [Selective embolization of hepatic arteries--an additional precaution to control
      hemorrhage in the management of severe liver trauma].
AB  - Two cases of severe hepatic injury in which selective hepatic artery embolization
      was used to control hemorrhage are presented. The first case is that of a 35 year
      old patient who sustained a severe liver injury after a car accident. A CAT scan
      of the abdomen revealed an AAST grade 5 liver injury, pooling of contrast
      material within the liver parenchyma, and blood within the peritoneal cavity. The
      patient was given fluid resuscitation and taken to angiography where bleeding
      from branches of the right hepatic artery was demonstrated. While angiography was
      being undertaken the hemodynamic status of the patient deteriorated, blood
      transfusion was started, and a selective embolization of the right hepatic artery
      was performed. The bleeding stopped promptly and hemodynamic stability was
      regained. The second case is that of a 40 year old pedestrian run over by a car.
      Abdominal ultrasound revealed free fluid in the peritoneal cavity and the patient
      was rushed to the O.R. Crushed right lobe of the liver, and inferior vena cava
      and bowel tears were found. After perihepatic packing and resection of the right
      and sigmoid colons retrohepatic vena cava tear was repaired and perihepatic
      packing restored. The abdominal cavity was closed and the patient was taken to
      the ICU for the correction of hypothermia, metabolic acidosis, and coagulopathy
      that had developed during the surgery. After 8 hours in the ICU the patient was
      transferred for angiography and a selective embolization of branches of the right
      hepatic artery was performed. The clinical course of the patients after
      angiographic embolization of the hepatic arteries is described and the literature
      that discusses the use of angiography and embolization of hepatic arteries after
      traumatic hepatic bleeding is reviewed.

PMID- 11303342
TI  - [Interactive health databases on the Internet].
AB  - In order to obtain reliable, comprehensive and current data, information systems
      which enable flexible presentation or analysis are necessary, as opposed to
      static tables. On-line and interactive numeric health databases on the Internet
      are increasingly available. Interactive tables can be produced in many fields,
      e.g., mortality, hospitalizations, cancer incidence, or motor vehicle accidents.
      The query screens are user-friendly and they can access remote, computerized
      data. Thus, it is possible to receive immediate responses to specific questions
      from national or international datasets, which can then be compared with local
      data--all without leaving one's chair. The aim of this review is to increase
      awareness of the existence of numeric health databases on the Internet, and their
      contribution to epidemiological research.

PMID- 11303341
TI  - [Pseudomembranous colitis: clinical, endoscopic and radiological correlation--a 2
      year experience].
AB  - The incidence rates of pseudomembranous colitis are rising. Early diagnosis and
      treatment are required for management of this potentially life-threatening
      disease. This report outlines our 2-year experience (1997-1998) at the
      gastrointestinal institute with 43 patients diagnosed with pseudomembranous
      colitis and describes the clinical course and imaging studies. The group
      consisted of 25 women and 18 men, aged 34-93 years (mean: 67). Thirty-nine
      patients were treated with antibiotics. Twelve patients were referred directly to
      an endoscopic examination with a presumed clinical diagnosis of pseudomembranous
      colitis (diarrhea, fever and abdominal pain) that was confirmed by colonoscopy.
      Thirty-one were referred to colonoscopy following abdominal imaging performed to
      clarify cause of fever and abdominal pain. Twenty-nine patients had an abdominal
      CT, one had an US and one a barium follow-through. The CT finding suggesting
      pseudomembranous colitis included colonic mural thickening in 28 patients (71%
      diffuse versus 29% segmental colitis), with an average wall thickness of 16 mm.
      Sixteen patients (59%) had pericolonic fat changes and 15 patients (51%) had
      ascites. All of these patients, except one, had endoscopic findings consistent
      with pseudomembranous colitis. Five patients (11.6%) died due to the severe PMC.
      To conclude, as an abdominal CT is often performed in the acutely ill patient, it
      may arouse the diagnosis of pseudomembranous colitis in the proper clinical
      setting. Such a suspected diagnosis justifies endoscopic evaluation, which is the
      most reliable diagnostic examination.

PMID- 11303343
TI  - [Malignant humoral hypercalcemia associated with angiotropic large B cell
      lymphoma].
AB  - Angiotropic large B cell lymphoma (angiotropic LCL) or intravascular large cell
      lymphoma (IVLCL) was diagnosed by liver and bone marrow biopsies and
      immunohistochemical studies in a 52 year old Caucasian male. IVLCL is a very rare
      disease characterized by widespread intravascular proliferation of lymphoma
      cells. Although it most commonly affects the central nervous system or skin and
      occasionally bone marrow, angiotropic LCL may be present without evidence of
      localized disease, as seen initially in our patient. To date, only a few cases of
      intravascular malignant lymphomatosis associated with parathyroid hormone related
      protein (PTH-rP) induced humoral hypercalcemia have been published. Our
      extraordinary case was diagnosed mainly by liver biopsy. The neoplastic lymphoid
      cells stained diffusely and strongly positive with CD-20 (Pan B) and were
      negative for CD-3 (Pan T) immunostain. The most significant, initial clinical
      finding was severe, unexplained hypercalcemia (until 18.6 mg/dl). Plasma PTH-rP
      showed a ten-fold increase at 8 pmol/L (normal value less than 0.8 pmol/L). Very
      unusual cytogenic abnormalities were found. The patient received the massive
      third generation combination chemotherapy comprising of Methotrexate,
      Doxorubicine, Cyclophosphamide, Vincristine, Prednisone and Bleomycin and
      developed, complete although temporary, clinical, humoral and cytogenetic
      remission.

PMID- 11303344
TI  - [The effect of gastro-esophageal reflux therapy on respiratory diseases in
      children].
AB  - In order to examine the effect of reflux therapy on Hyper Reactive Airway Disease
      (HRAD) and apnea severity, 107 children, 78 with HRAD and 29 with apnea,
      underwent pH monitoring in the Pediatric Surgery Unit of Wolfson Hospital and the
      Dana Children's Hospital during the years 1995-1998. Pathological reflux was
      defined by means of the Boix-Ochoa and RI (Reflux Index) scores. In patients with
      positive reflux, anti-reflux treatment was initiated. Prior to and following pH
      monitoring, the respiratory status of all patients (both with and without reflux)
      was evaluated by a pediatric pulmonologist employing commonly used scores to
      determine severity. RESULTS: Subject age ranged between one day and 15 years
      (mean: 15.44 +/- 29 months, median: 6.37 months). In HRAD, following anti-reflex
      treatment the reflux positive group showed a significant score improvement, from
      an average of 2.9 +/- 1.1 units to 1.54 +/- 1.2 units (p < 0.0001); a decrease in
      the number of patients treated with oral corticosteroids (p < 0.01); a close to
      significant decrease (p = 0.069) in the average dose of inhaled corticosteroids;
      and a decrease in the number of patients using bronchodilators (p = 0.042). The
      reflux-negative group, not treated for reflux, displayed no significant
      improvement, with only a decrease in the severity scores from 2.44 +/- 1.0 to
      1.78 +/- 1.2 units (p = 0.14), and no change on any of the other parameters. In
      apnea, all patients improved, from an average score of 2.34 +/- 0.77 to 0.03 +/-
      0.19 units (p < 0.0001), with no significant difference between the reflux
      positive and the reflux negative groups. In view of these findings, it is
      postulated that anti-reflux therapy may have an additive effect on HRAD severity,
      beyond that of spontaneous respiratory improvement. We therefore find it
      appropriate for every severe HRAD patient (frequent exacerbations or high
      corticosteroid dose) to undergo pH monitoring in order to treat those with proven
      reflux. In respect to apnea, we cannot attribute any significance to the
      existence of reflux or to anti-reflux treatment.

PMID- 11303345
TI  - [Laparoscopic adrenalectomy for pheochromocytoma].
AB  - Laparoscopic adrenalectomy has recently been shown to be a safe and effective
      strategy of treating a variety of benign adrenal tumors. The ability to reduce
      hypertensive crisis during surgery for pheochromocytoma by adequate preoperative
      alpha- and beta-blockade and early intraoperative venous ligation have reached a
      level sufficient to permit a safe laparoscopic approach. During the period
      January 1995 to December 1999, laparoscopic adrenalectomy was attempted in twelve
      patients with unilateral pheochromocytoma and in 2 patients with multiple
      endocrine neoplasia type II. All procedures were completed laparoscopically. The
      mean operative time was 90 minutes (45-120). Blood transfusion was not required
      and there were no postoperative complications. The median hospital stay was 3
      days.

PMID- 11303346
TI  - [Colonic pseudo-obstruction (Ogilvie syndrome) following cesarean section].
AB  - Acute colonic pseudo-obstruction, or Ogilvie syndrome can be a major surgical
      complication. Ogilvie syndrome, unlike adynamic ileus, is usually not self
      limiting and may cause ischemic necrosis and colonic perforation, with a
      mortality rate as high as 50 percent. Ogilvie syndrome represents a diagnostic
      and therapeutic challenge that deserves a multidisciplinary approach. We present
      a case report and a literature review of the syndrome.

PMID- 11303347
TI  - [Pleomorphic carcinoma of the lung heralded as bilateral leg pain].
AB  - This is a case of a 70 year old male patient suffering from bilateral leg pain
      for 2 months. Physical examination disclosed clubbing. X-rays of the legs showed
      bilateral periosteal elevation with subperiosteal bone formation. 99TM
      diphosphonate bone scan was negative. A search for malignancy revealed
      pleomorphic carcinoma of the right lung. Pain symptom disappeared 2 days after
      resection of the tumor. Repeated X-rays of the legs, three and a half months
      later showed no change and the clubbing persisted. Hence, unexplained bilateral
      leg pain should raise suspicion of hypertrophic osteoarthropathy, and elicit a
      search for secondary disease especially lung tumor. It is interesting to point
      out the negative bone scan and the rapid resolution of patient symptoms after
      resection of the tumor.

PMID- 11303348
TI  - [Attitude of hospital visitors towards cigarette smoking inside hospital
      buildings; one more step towards a "smoke free hospital" in Israel].
AB  - In order to determine a policy within the hospital restricting smoking we
      previously surveyed the attitude of the hospital staff towards smoking inside the
      hospital buildings. In the present survey we examined the attitude of the
      hospital visitors on the same issue. One hundred and fifty-seven hospital
      visitors participated in the survey and answered a questionnaire; 93 visitors
      were smokers, 64 were non-smokers. Eighty-eighth percent of the visitors smoked
      during their visit, 4 cigarettes on the average, during an average length of stay
      of 2.8 hours, until completing the questionnaire. Eighty-three percent of the
      smokers were aware of the law that prohibits smoking in public buildings, and 71%
      were aware of the signs and advertisements that prohibit smoking in the hospital.
      Two thirds of the smokers declared that they would have refrained from smoking in
      the hospital if others around them also refrained from smoking and justified the
      law that prohibits smoking in public buildings, including hospitals. Sixty-nine
      percent of the smokers declared that they were willing to cooperate with hospital
      management in restricting smoking to the hospital grounds outside the hospital
      buildings, and would accept directives regarding smoking restriction from any
      hospital personnel. In fact, only 11% of the smokers were requested to stop
      smoking during their visit. These findings reinforce the results of our pervious
      survey conducted among the hospital staff and indicates the existence of a
      paradoxical vicious cycle of behavior among smokers and non-smokers, visitors and
      staff, in the hospital. On the one hand the smokers do not have the self
      obedience necessary to stop smoking while visiting in the hospital, although they
      are aware of their misdeed. On the other hand the non-smokers lack the confidence
      that they will obtain the cooperation of the smokers, although the smokers are
      willing to cooperate. Both groups except someone else to either actively restrict
      them from smoking or to encourage them to restrict the smokers. Our findings
      suggest that this "someone else" is the hospital management (and the staff
      endorsed to implement this directive).

PMID- 11303349
TI  - [Eppur si muove (Galileo Galilei 1564-1642): the idiotypic dysregulation of
      autoantibodies as part of the etiology of SLE].

PMID- 11303350
TI  - [Mass casualty events during night shifts in the internal medicine departments].

PMID- 11303351
TI  - [Autoimmune and rheumatic features and malignancies].

PMID- 11303352
TI  - [Immune thrombocytopenic purpura in pregnancy].

PMID- 11303353
TI  - [Violence and homicide in psychotic patients--is this a variable phenomenon?].

PMID- 11303354
TI  - [Tardive dyskinesia: etiology, clinical features and therapy].

PMID- 11303355
TI  - [Aging and thermoregulation].

PMID- 11303356
TI  - [Local excision of distal rectal carcinomas].

PMID- 11303357
TI  - [Ultrasonographic investigation of fetal cardiac venous return].

PMID- 11303358
TI  - [Antenatal follow-up and the attitude to a newborn of a mother with a positive
      VDRL test].

PMID- 11303359
TI  - [Risk factors for falls in the elderly].

PMID- 11303360
TI  - [Chapters in the history of psychiatry in Palestine and its neighborhood].

PMID- 11303362
TI  - [The international conflict in setting priorities in health care].

PMID- 11303361
TI  - [Dream or reality].

PMID- 11303363
TI  - [The 13th International Congress for Medicine and Law, Helsinki Finland, 6-10
      August, 2000].

PMID- 11303364
TI  - Consumer choice in health coverage: a mixed blessing.

PMID- 11303365
TI  - The effectiveness of adult day services for disabled older people.
AB  - Adult day care has attracted a considerable amount of attention among
      researchers, practitioners, and policymakers. However, there have been few
      efforts to synthesize empirical results. This paper reviews research that
      determines the effectiveness of adult day services in improving client
      functioning, alleviating caregiver stress, and delaying nursing home placement.
      In addition, the strengths and limitations of the research are considered. This
      paper concludes with a discussion of policy-relevant issues that must be
      addressed when determining the effectiveness of adult day services.

PMID- 11303366
TI  - Providing information to help Medicare beneficiaries choose a health plan.
AB  - Many Medicare beneficiaries have limited knowledge of the Medicare program and
      related health insurance options. This is due in part to the complexity of the
      Medicare program and supplemental health insurance market. A recent congressional
      mandate through the Balanced Budget Act of 1997 called for broad dissemination of
      information to educate beneficiaries about their health plan options and to
      encourage informed health plan decision-making. In response, the Health Care
      Financing Administration (HCFA) launched the National Medicare Education Program
      (NMEP) to support the educational objectives of the BBA. This paper provides an
      overview of the components of the NMEP information campaign. We also review
      lessons learned from our experience in designing and testing a prototype consumer
      handbook that explains the different health plan options to Medicare
      beneficiaries. Through our discussion of the handbook, we highlight several ways
      to communicate information effectively about a complex publicly funded program to
      an older adult population.

PMID- 11303367
TI  - Primary prevention for older adults: no longer a paradox.

PMID- 11303368
TI  - A comprehensive policy analysis of and recommendations for senior center gambling
      trips.
AB  - Gambling is one of the fastest growing industries in America. Public support is
      high for legalized gambling among all age groups. Because gambling is growing in
      popularity as an activity among those 65 and over, many senior centers are
      beginning to offer group trips to casinos and other gambling attractions such as
      dog tracks. This paper analyzes senior center casino gambling trips, with
      particular attention to the number of trips offered, how trips are funded, the
      policy implications of offering trips, and policy alternatives for state and
      local policymakers. Data for the study come from personal interviews with
      activity directors of 16 senior centers across Massachusetts and a formal survey
      of 30 additional senior centers in Central Massachusetts. Benefits of a new
      policy option, a public education strategy, are also reviewed.

PMID- 11303369
TI  - A Foucauldian analysis of old age and the power of social welfare.
AB  - It is argued that the question of social welfare is a key, if often overlooked,
      component in the construction of power relations and identities in later life
      that can take its place next to debates on bioethics and consumer lifestyle.
      Foucault's (1977) claim, that identities are kept in place through the deployment
      of integrated systems of power and knowledge and a routine operation of
      surveillance and assessment, is critically examined in this context. Trends in
      social welfare in the United Kingdom are used as a case example that sheds light
      on wider contemporary issues associated with old age. Finally, implications for
      the creation of particular narratives about later life are discussed and grounded
      through Foucault's (1988) notion of "technologies of self."

PMID- 11303370
TI  - The effect of culture results for Helicobacter pylori on the choice of treatment
      following failure of initial eradication.
AB  - BACKGROUND: Current treatment for the eradication of Helicobacter pylori in
      patients with peptic disease is based on the combination of antibiotic and anti
      acid regimens. Multiple combinations have been investigated, however no consensus
      has been reached regarding the optimal duration and medications. OBJECTIVES: To
      assess the efficacy of two treatment regimens in patients with peptic ulcer
      disease and non-ulcer dyspepsia, and to determine the need for gastric mucosal
      culture in patients failing previous treatment. METHODS: Ninety patients with
      established peptic ulcer and NUD (with previously proven ulcer) were randomly
      assigned to receive either bismuth-subcitrate, amoxycillin and metrnidazole (BAM)
      or lansoprasole, clarithromycine and metronidazole (LCM) for 7 days. Patients
      with active peptic disease were treated with ranitidine 300 mg/day for an
      additional month. RESULTS: Eradication failed in 8 of the 42 patients in the BAM
      group and in 2 of the 43 patients in the LCM group, as determined by the 13C urea
      breath test or rapid urease test (19% vs. 5%, respectively, P = 0.05). Five of
      these 10 patients were randomly assigned to treatment with lansoprazole,
      amoxycillin and clarithromycin (LAC) regardless of the culture obtained, and the
      other 5 patients were assigned to treatment with lansoprazole and two
      antibacterial agents chosen according to a susceptibility test. Eradication of H.
      pylori was confirmed by the 13C urea breath test. The same protocol (LAC) was
      used in all patients in the first group and in four of the five patients in the
      second group. The culture results did not influence the treatment protocol
      employed. CONCLUSIONS: Combination therapy based on proton pump inhibitor and two
      antibiotics is superior to bismuth-based therapy for one week. Gastric-mucosal
      culture testing for sensitivity of H. pylori to antibiotics is probably
      unnecessary before the initiation of therapy for patients with eradication
      failure.

PMID- 11303371
TI  - Ultrasonographic measurements of fetal femur length and biparietal diameter in an
      Israeli population.
AB  - BACKGROUND: Charts of fetal measurements are widely used in the follow-up of
      pregnant women, however no charts have been constructed for the Israeli
      population. OBJECTIVES: To establish growth charts for fetal femur size and
      biparietal diameter. METHODS: A prospective cross-sectional study of 1,422
      singleton pregnancies was conducted. RESULTS: A total of 1,143 pregnancies met
      the inclusion criteria. Femur length and biparietal diameter were measured. A
      linear cubic model was fitted to construct growth charts for the different
      centiles. The charts were compared with previously published data. CONCLUSIONS:
      We have constructed new fetal measurement charts for femur length and biparietal
      diameter that are unique for the Israeli population. These charts have been found
      to be similar to those published for other Caucasian populations.

PMID- 11303372
TI  - Bolus high dose interleukin-2 for the treatment of malignant melanoma.
AB  - BACKGROUND: High dose interleukin-2 therapy, administered in bolus, is considered
      to be a reasonable treatment option in a selected group of patients with
      metastatic malignant melanoma. OBJECTIVES: To present our experience using this
      mode of therapy in 21 patients with metastatic melanoma. MATERIALS AND METHODS:
      The 21 patients in our study group comprised 13 men and 8 women with a mean age
      of 46 years (range 29-63). Their metastatic disease was present in all
      extracranial sites, dermal and sub-dermal metastases being the most common (15
      patients had at least one site, in addition to other locations of metastases).
      Patients with intracranial disease were excluded due to the poor effectivity of
      IL-2 at this site. Treatment comprised a course of 2 weeks of therapy with a 1
      week rest interval between. Radiological and physical evaluation was performed 6
      8 weeks after the first course. If a response was achieved a second course of
      therapy was given. Patients received up to 14 planned doses of IL-2 in each week,
      720,000 IU/kg of IL-2 per dose i.v. in 15 minutes. All treatments were given in
      the surgical ward, and only one patient was hospitalized in the intensive care
      unit. RESULTS: Of the 21 patients, one had a complete response that has lasted
      for 17 months and 5 patients had a partial response (range 3 months to 3 years).
      One patient died during treatment, and one patient who refused further treatment
      because of no response died a few days after completion of treatment. Prior to
      therapy three of the responders had received autologous vaccines with good
      immunological response (P = 0.115). Toxic side effects were significant, but they
      were treated successfully with no residual damage. CONCLUSIONS: High dose IL-2
      can be administered safely in a surgical department. The response rates achieved
      in this series justify the use of high dose IL-2 in a selected group of patients.
      To improve response rates, a combination of autologous vaccines prior to high
      dose IL-2 may be recommended.

PMID- 11303373
TI  - Hepatitis C infection in dialysis patients in Israel.
AB  - BACKGROUND: Hepatitis C virus is the major cause of acute and chronic hepatitis
      in patients with end-stage renal disease receiving replacement therapy.
      OBJECTIVES: To define the prevalence of HCV RNA in a population of patients on
      dialysis in Israel, to determine the relative risk of acquiring HCV infection
      while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to
      define the HCV genotypes in this population. METHODS: During 1995 we studied 162
      dialysis patients. Information was obtained regarding the mode of dialysis, years
      of treatment, number of blood transfusions, and results of serological testing
      for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies
      were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was
      determined by polymerase chain reaction. HCV genotyping was performed by a
      hybridization assay. RESULTS: HCV RNA was detected in 18% of the HD group and 7%
      of the CAPD group. The number of HCV RNA-positive patients was significantly
      higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients
      were treated longer than the HCV RNA-negative patients (P < 0.02). CONCLUSIONS:
      Third-generation immunoassay proved to be highly sensitive (94%) and specific
      (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, 1b
      being the most frequent. Identification and isolation of infected HCV patients
      may minimize its spread in dialysis units and prevent cross-infection.

PMID- 11303374
TI  - Congenital subependymal pseudocysts: own data and meta-analysis of the
      literature.
AB  - BACKGROUND: Congenital subependymal pseudocysts are incidental findings that are
      found in 0.5-5.2% of neonates during postmortem examination or head
      ultrasonography. In our institution we detected 10 neonates with CSEPC.
      OBJECTIVE: To investigate associated etiological factors, morphologic
      characteristics and outcome of CSEPC. METHODS: We performed a meta-analysis of
      the literature on CSEPC (1967-98), including our 10 cases. RESULTS: A total of
      256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC; 48.8% were
      bilateral and 53.4% were located in the caudothalamic groove or head of caudate
      nucleus. Altogether, 93.5% resolved during 1-12 months of ultrasonographic follow
      up. Compared to the general neonatal population, the following features were more
      prevalent in the CSEPC population: prematurity, maternal vaginal bleeding,
      preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal
      cytomegalovirus and rubella infections, congenital malformations, chromosomal
      aberrations, infant mortality, and neurodevelopmental handicap. The risk for
      neurodevelopmental handicap was significantly higher when CSEPC were associated
      with fetal infections, IUGR, malformations and chromosomal aberrations, or
      persistence of CSEPC during follow-up. CSEPC infants without any of these four
      conditions had a low risk for neurodevelopmental handicap. CONCLUSIONS: CSEPC are
      morphologic features of various underlying conditions encountered in the fetus.
      Association of CSEPC with IUGR, fetal infections, malformations and chromosomal
      aberrations or persistence of CSEPC indicates a higher risk for future
      neurodevelopmental handicaps, probably because of the deleterious effects on the
      fetal brain that are inherent in these conditions. A favorable outcome is
      expected in the absence of these risk factors.

PMID- 11303375
TI  - Characteristics of clients attending confidential versus anonymous testing
      clinics for human immunodeficiency virus.
AB  - OBJECTIVES: To compare risk behavior between subjects attending anonymous and
      confidential clinics for human immunodeficiency virus testing, and to assess
      whether anonymous testing results in a higher accrual of persons at risk for HIV.
      METHODS: An anonymous questionnaire that addressed sociodemographic and risk
      behavior aspects was administered to 140 subjects attending an anonymous clinic
      and 124 attending a confidential clinic in the Tel Aviv area. A logistic
      regression analysis was used to compare the effects of various behavioral factors
      on the probability of attending each clinic. RESULTS: Chronological age, age at
      first sexual intercourse, and the percent of married subjects were similar in
      both clinics. However, there was a significant difference in the sex ratio and in
      educational attainment (85.0% versus 55.6% were males, P < 0.001; and 58% vs. 34%
      had over 12 years of education, P < 0.001, in the anonymous and confidential
      clinics respectively). There was a striking difference between the two clinics
      with regard to sexual experience characteristics: of the subjects reaching the
      anonymous clinic 21.4% were homosexual and 10.0% bisexual versus a total of 2.6%
      in the confidential clinic. A logistic regression analysis, comparing the effects
      of various behavioral factors on the probability of attending each clinic, showed
      that gender (male), high education, homosexuality, number of partners and sexual
      encounter with sex workers were the strongest predictors for selecting anonymous
      HIV examination. CONCLUSIONS: Individuals at high risk for HIV, such as
      homosexuals and bisexuals, prefer to attend an anonymous clinic.

PMID- 11303376
TI  - Autism in the Haifa area--an epidemiological perspective.
AB  - BACKGROUND: Autism is a pervasive developmental disorder. The incidence rate and
      other related epidemiological characteristics of the Israeli population are not
      available. OBJECTIVES: To assess the incidence rate of autism in the Haifa area
      and to compare family characteristics with previous reports from other countries.
      METHODS: We approached facilities in the Haifa area that are involved with the
      diagnosis and treatment of autism. The study group comprised children born
      between 1989 and 1993. Records of the children were scrutinized and 69% of the
      mothers were interviewed. Live-birth cohorts of the same years were employed for
      incidence computation. RESULTS: An incidence rate of 1/1,000 was derived. Male to
      female ratio was 4.2:1. Pregnancy and perinatal periods were mostly uneventful. A
      low prevalence of developmental and emotional morbidity was reported for family
      members. CONCLUSIONS: The epidemiological characteristics found in the Haifa area
      are similar to those reported from non-Israeli communities. This finding supports
      an underlying biological mechanism for this disorder. These data can be used for
      future trend analyses in Israel.

PMID- 11303377
TI  - Prevalence of self-reported allergic conditions in an adult population in Israel.
AB  - BACKGROUND: Asthma, allergic rhinitis, and atopic dermatitis are leading causes
      of chronic diseases in developed countries, with at least one allergic condition
      troubling 10 to 20% of the general population. The few studies performed in
      Israel determined the prevalence of allergic conditions in selected populations
      (schoolchildren and soldiers); no study representative of the general population
      has previously been done. OBJECTIVES: To determine the prevalence of allergic
      conditions in the general population in Israel and the differences between ethnic
      and socioeconomic groups. METHOD: Using a computer-assisted telephone interview,
      a telephone questionnaire was conducted in a representative sample of the general
      Israeli population. RESULTS: Of the population studied, 14% claimed to have
      bronchial asthma, 14% allergic rhinitis, and 6% other allergic conditions.
      Prevalence rates were higher in the Israeli Arab population and in those with low
      income and low education levels. Of those with allergic conditions, 58% were
      treated by a primary physician, 32% were not treated at all, and only 10% were
      treated by a different specialist physician. CONCLUSIONS: The prevalence of
      allergic conditions in this study concurs with that found by other studies in
      developed countries. Allergic conditions are higher in the Israeli Arab
      population and in those with low income and low education level.

PMID- 11303378
TI  - Parental knowledge and views of pediatric congenital heart disease.
AB  - BACKGROUND: Parental knowledge of their child's heart disease, while often
      overlooked, contributes to compliance and reduces anxiety. Prior studies have
      shown that 36% of parental diagnostic descriptions are incorrect. OBJECTIVES: To
      assess parental knowledge and attitudes among outpatients at a hospital pediatric
      cardiology clinic. METHODS: Seventy-four families completed a questionnaire in
      which they described their child's condition and stated their attitude towards
      dental hygiene and future prenatal diagnosis. RESULTS: Eighteen percent of the
      parents failed to describe their child's malformation correctly. We found that
      parental understanding of the heart defect correlated with parental education.
      Future prenatal diagnosis was considered by 88% of families, and termination of
      pregnancy by 40%. Only 40% of children were aware of their heart problem.
      Children of parents who were ignorant about the condition tended to lack
      knowledge themselves. An additional finding was that 68% of Jewish families turn
      to non-medical personnel for medical advice--an interesting finding not hitherto
      addressed. CONCLUSIONS: Ignorance of their child's problem did not correlate with
      its severity or complexity but rather with parental background: the less educated
      the parent, the more likely was the problem perceived incorrectly.

PMID- 11303379
TI  - Transesophageal echocardiography--an overview.

PMID- 11303380
TI  - Fexofenadine hydrochloride--a new anti-histaminic drug.

PMID- 11303381
TI  - Oncogenic potential of human neurotropic virus: laboratory and clinical
      observations.
AB  - Cancer is a multi-step disease involving a series of genetic alterations that
      result in the loss of control of cell proliferation and differentiation. Such
      genetic alterations could emerge from the activation of oncogenes and the loss or
      malfunctioning of tumor suppressor gene activity. Our understanding of cancer has
      greatly increased through the use of DNA tumor viruses and their transforming
      proteins as a biological tool to decipher a cascade of events that lead to
      deregulation of cell proliferation and subsequent tumor formation. For the past
      ten years our laboratory has focused on the molecular biology of the human
      neurotropic papovavirus, JCV. This virus causes progressive multifocal
      leukoencephalopathy, a fatal neurodegenerative disease of the central nervous
      system in immunocompromised patients. JCV is a common human virus that infects
      more than 80% of humans but does not induce any obvious clinical symptoms. The
      increased incidence of acquired immune deficiency syndrome and the use of
      immunosuppressive chemotherapy have dramatically raised the incidence of PML. The
      coincidental occurrence of malignant astrocytes and oligodendrocytes in PML
      patients, coupled with the induction of glioblastoma in JCV-infected nonhuman
      primates, provides intriguing speculation on the association between JCV and CNS
      malignancies. In this report we discuss clinical data and laboratory observations
      pointing to the direct involvement of JCV in cancer.

PMID- 11303382
TI  - Mast cells and atherosclerosis.

PMID- 11303383
TI  - Recurrent deglutition syncope.

PMID- 11303384
TI  - Beryllium disease: first case reported in Israel.

PMID- 11303385
TI  - Arterial thromboembolism from a distal aortic thrombus in a patient with Crohn's
      disease.

PMID- 11303386
TI  - Segmental resection for recurrent carcinoma of the esophagus.

PMID- 11303387
TI  - Cecal ulceration due to methotrexate.

PMID- 11303388
TI  - Epidemiological trends of pediatric emergency referrals in Israel.
AB  - BACKGROUND: In the last decade pediatric emergency medicine in Israel advanced to
      a stage of independent emergency pediatric departments. At the same time,
      injuries and childhood, trauma--a global health problem--became the main cause of
      mortality and emergency referrals in children over the age of one year.
      OBJECTIVE: To determine the extent of pediatric referrals to emergency
      departments and the rate of pediatric trauma referrals in Israel. METHODS: The
      records from EDs of Israel's 24 public hospitals for a 6 year period (1994-99)
      were collected. The records based on computerized ED records were used to
      identify the basic demographics of pediatric ED referrals. Routine data for all
      pediatric patients were collected from pediatric and general EDs. This study is
      an analysis of the accumulated anonymous ED databases. RESULTS: Pediatric
      referrals to EDs accounted for 2,907,912 patients, 37% of them due to trauma. The
      mean hospitalization rate was 21%. No significant changes were observed during
      the 6 years in the rate of pediatric ED referrals and in the ED hospitalization
      rate of children. There is a constant trend of increase in trauma referrals of
      children. CONCLUSIONS: The ED is a major site for the delivery of healthcare to
      children in Israel. One of every four children in the community is referred every
      year to an ED, and more than one-third of those referrals are due to trauma.

PMID- 11303389
TI  - The 15th Rappaport Symposium. Immune-mediated brain injury and repair: mechanisms
      and therapies. 15-16 June 2000, Haifa, Israel.

PMID- 11303390
TI  - [Treatment of Crohn's disease with anti TNF alpha antibodies--the experience in
      the Tel Aviv Medical Center].
AB  - TNF alpha is a pro-inflammatory cytokine in Crohn's disease and it's
      neutralization is beneficial in patients with active disease. Remicade is a
      chimeric monoclonal anti-TNF antibody. Remicade is used in our center since
      December 1998 in 13 patients who were treated for active disease or fistula. We
      followed the patients and treatment results in order to estimate the efficacy and
      safety of this preparation. Response to treatment was measured by the Crohn's
      Disease Activity Index (CDAI) in patients treated due to active disease, or by
      the presence of discharge from external fistulae. Five out of seven patients with
      fistulae had less or no discharge after completing a course of 3 infusions. Four
      out of 6 patients treated due to active disease improved significantly after a
      single infusion. Five out of the six needed additional injections due to symptom
      recurrence. Intervals between infusions were 2 weeks--for fistulae patients to 32
      weeks for patients with active disease. Adverse events for the 13 patients were
      usually mild except for 4 patients that suffered from anaphylactic shock,
      disseminated eruption (2) and eosinophilic pneumonitis. In summary, treatment of
      patients with active Crohn's disease or fistulae with monoclonal anti-TNF
      antibodies is an effective and relatively safe option after established treatment
      has failed. Analyzing the results of on going clinical trials and of the patients
      treated off-protocol will enable to establish new treatment strategies for
      patients with active Crohn's disease and fistulae.

PMID- 11303391
TI  - [Management of nasal meningoencephaloceles and cerebrospinal rhinorrhea].
AB  - CSF rhinorrhea constitutes a diagnostic challenge. If unrecognized or
      incompletely managed, it can result in devastating complications. The physician
      must e aware to this entity and it's management. The conventional neurosurgical
      management of meningoencephaloceles and cerebrospinal rhinorrhea has been by the
      intracranial approach. Otolaryngologists have undertaken extracranial approaches
      for repair of these problems with fair results. In recent years, functional
      endoscopic sinus surgery has gained popularity and was advocated for the repair
      of nasal meningoencephaloceles and CSF fistulae. Between 1998 and 1999, five
      patients were operated by the senior author (M.P) by means of endoscopic sinus
      surgery. His success rate and lower morbidity make this approach the treatment of
      choice. The perioperative use of fluoroscein allows us to locate precisely the
      defect and to confirm complete sealing of the leak. We present our experience in
      managing 5 cases, 3 of which presented with meningoencephaloceles.

PMID- 11303392
TI  - [Neurological manifestations in West Nile fever].
AB  - The West Nile fever is a viral disease transferred by a mosquito bite. It is well
      known in the world for the last 70 years. Recently, there was an outbreak of this
      disease in Israel. We will describe case reports of 2 patients who were afflicted
      by the disease. The first one was hospitalized with an unusual presentation
      including paralysis to the lower limbs, while the second one was admitted with
      meningitis. In both, the course was quite dramatic, and one of them expired.
      Reviewing the literature revealed that neurological manifestations are quite
      frequent among these patients (90%), while in elder people, they were fatal.

PMID- 11303393
TI  - [Characteristics of nasopharyngeal carriage of Streptococcus pneumoniae in
      children during acute respiratory disease].
AB  - Streptococcus pneumoniae is an important cause of pediatric morbidity and its
      main reservoir is the nasopharynx, from which it can disseminate and cause
      invasive disease. From November 1997 through March 1998, nasopharyngeal carriage
      of S. pneumoniae was evaluated in 250 children under the age of 36 months: 123
      Jews and 127 Bedouins with acute respiratory disease and in 980 healthy control
      children (852 Jews and 128 Bedouins). Carriage rate was higher among sick
      children. Among Jewish children it was 57% and 35% of sick and healthy children
      respectively (p < 0.01), and among Bedouin children it figured as 80% and 67%
      respectively (p = 0.01). The difference in carriage rate was most prominent in
      infants under the age of 5 months: among Jewish children it was 60% and 27% of
      sick and healthy children respectively (p < 0.001) and among Bedouins it was 82%
      and 65% respectively (p = 0.05). Higher carriage rate of penicillin resistant
      pneumococci (PRP) was also detected in sick children, with no relation to
      antibiotic treatment in the month prior to sampling. In Jewish children PRP was
      detected in 12%, 28% (p < 0.001) and 36% (p < 0.001) of healthy children, sick
      children with previous antibiotic treatment and sick children with no treatment,
      respectively. The seroypes included in the newly developed 7-valent conjugate
      vaccine: 4, 6B, 9V, 14, 18C, 19F, 23F, that are highly pathogenic and often
      antibiotic resistant contributed 74% of isolates in sick Jewish children who had
      previous antibiotic treatment and 39% of isolates in healthy children (p <
      0.001). In Bedouin children vaccine types carriers rate among the sick children
      was not higher than in healthy children. Acute respiratory disease increases the
      risk of pneumococcal carriage in general and carriage of resistant pneumococci in
      particular. Previous antibiotic treatment increases the risk of carring one of
      the pathogenic serotypes included in the 7-valent vaccine. The impact of disease
      is most prominent in infants under 5 months, since they are usually less exposed
      to S. pneumoniae carriers than older children. Since the increase in carriage
      rate during illness is mostly due to the serotypes included in the newly
      developed conjugate vaccine, future immunization programme may decrease not only
      morbidity rate but also nasopharyngeal carriage rate of pneumococci in general
      and of antibiotic-resistant pneumococci in particular.

PMID- 11303394
TI  - [Computed tomographic angiography of the peripheral vasculature--role and
      applications in vascular surgery].
AB  - Computed tomographic angiography (CTA) is a relatively new diagnostic modality in
      the field of vascular surgery. Despite being new it has already been introduced
      into a wide range of diagnostic applications in this field and in many cases it
      can precede or replace the conventional intra-arterial angiography. During a 12
      month period between 1.8.98 and 1.8.99 sixty five peripheral arterial imaging
      scans were performed using a CT Twin--2 helical scanner (Spiral Twin Flash.,
      Elscint, Israel) with a 100% technical success rate and no complications at all.
      Twelve patients (18.5%) were operated upon and 20 (30.7%) underwent endovascular
      procedures with full intra-procedural agreement with the pre-operative or pre
      procedure CTA findings. Despite possible pitfalls and a few disadvantages the
      technique carries major benefits and significant advantages to both the patient
      and the clinician. Therefore we recommend considering CTA as a first line
      diagnostic modality whenever peripheral vasculature has to be demonstrated
      whether electively or urgently and to spare the conventional angiography for
      selected cases only.

PMID- 11303395
TI  - [The chemotherapeutic treatment of advanced Hodgkin's disease].
AB  - Between 1972 and 1994, 121 adult patients with advanced Hodgkin's disease
      received MOPP (M) combination chemotherapy, MOPP alternating with ABVD (M-A) or
      MOPP and ABV hybrid (M/A). Radiation therapy was given to 1/3 of them. The median
      age was 35 years, 58% had stage III and 42% had stage IV disease. Failure-free
      survival at 10 years was 43.9%. It was 66.7%, 48.4% and 29.9% for patients
      treated by M/A, M-A and M, respectively. Overall survival at 10 years was 40.8%,
      and 78.2%, 48% and 27.7% for patients treated by M/A, M-A and M, respectively.
      Multivariate analysis found age (above or below 65 years) and combination
      chemotherapy (with or without adriamycin) to be significant prognostic factors.
      M/A combination was more myelotoxic, while M combination caused more second
      primaries. Today, 80% of patients with advanced Hodgkin's disease may be cured,
      with low rate of long-term toxicity.

PMID- 11303396
TI  - [Biological compounds in the treatment of Crohn's disease].

PMID- 11303397
TI  - [Are we using enough sound clinical judgment in epilepsy?].

PMID- 11303398
TI  - [Ovarian hyperstimulation syndrome].

PMID- 11303399
TI  - [Matrix metalloproteinases involvement in diseases of the central nervous
      system].

PMID- 11303400
TI  - [Specific learning and cognitive deficits in neurofibromatosis type 1].

PMID- 11303401
TI  - [Gasless laparoscopy in gynecologic surgery].

PMID- 11303402
TI  - [Procalcitonin--a specific marker for severe bacterial infection and sepsis].

PMID- 11303403
TI  - [Leukotriene antagonists: additional treatment for chronic urticaria?].

PMID- 11303404
TI  - [Preemptive analgesia--is it achievable?].

PMID- 11303405
TI  - [Frequently asked questions about the effects of work during pregnancy].

PMID- 11303406
TI  - [Bupropion: a new hope for smokers willing to quit].

PMID- 11303407
TI  - [Radioactive therapy for the prevention of post angioplasty restenosis: a
      statement of the Invasive Working Group of the Israel Heart Society].

PMID- 11303408
TI  - Advancing the dermatologist's role in patient care.

PMID- 11303409
TI  - Sweeping trends transform the e-health landscape.

PMID- 11303410
TI  - Is your Web site ADA compliant?

PMID- 11303411
TI  - Influenza. Cost of illness and considerations in the economic evaluation of new
      and emerging therapies.
AB  - Influenza infection has been a burden to humans for thousands of years. Despite
      the fact that epidemics could be predicted with regularity, the lack of available
      prevention or treatment measures left humankind vulnerable to the harmful effects
      of this ubiquitous virus. While the pandemics of 1918 and 1957 are recent
      examples of the devastation that influenza may inflict, even in a typical year
      influenza infection and related complications cause significant morbidity and
      mortality. The development of an influenza vaccine during the 1940s marked a
      major turning point in the management of this disease. Vaccination of the elderly
      and other high risk patients has been shown to reduce morbidity and mortality and
      to be a worthwhile investment from an economic perspective. Despite these
      benefits, vaccine use in this group remains suboptimal. The role of annual
      vaccination for individuals at lower risk for influenza-related complications
      remains controversial. While prevention by vaccination is relatively
      straightforward, the treatment of symptomatic influenza-like illness with
      medication is more complicated. Differentiating symptoms caused by the influenza
      viruses from those caused by other common viruses is difficult. Currently
      available tests to document influenza as the cause of illness are either too
      expensive, too inaccurate or too time consuming to impact treatment. Symptom
      based diagnosis remains the most commonly used strategy in clinical practice. The
      approval of the neuraminidase inhibitors (NIs)--zanamivir and oseltamivir--remind
      healthcare providers of the difficulties in diagnosing and treating influenza.
      NIs have been shown to reduce the duration of symptoms of individuals infected
      with influenza when prescribed within the first 2 days of symptoms. Whether these
      innovative agents are cost effective, however, requires a more detailed
      understanding of the benefits that these agents may offer above and beyond
      existing therapies. In this review, we examine the burden of influenza infection,
      diagnostic challenges and the clinical and economic impact of available
      interventions. Clinical controversies and potential areas for further
      investigation are also explored.

PMID- 11303412
TI  - Workplace productivity. A review of the impact of migraine and its treatment.
AB  - Migraine is a common disorder characterised by recurrent episodes of disability.
      Despite the high prevalence of migraine, data have been lacking on its impact in
      a working population. The advent of new therapies has stimulated interest in this
      area, and evidence is now available that documents the substantial impact of
      migraine on workplace productivity and the likelihood of untreated migraine
      leading to unemployment or underemployment for the patient. This paper reviews
      current findings of both observational and interventional studies about the
      impact of migraine on productivity and employment. When considered in the light
      of migraine demographics, the high prevalence of migraine, and its low
      consultation and treatment rates, this evidence indicates that improved screening
      and treatment for this common condition could have a substantial impact on worker
      productivity and on patient well-being.

PMID- 11303413
TI  - Economic burden of chronic obstructive pulmonary disease. Impact of new treatment
      options.
AB  - The incidence, morbidity and mortality of chronic obstructive pulmonary disease
      (COPD) is rising throughout the world. The total economic cost of COPD in the US
      in 1993 was estimated to be over $US15.5 billion, with $US6.1 billion for
      hospitalisation, $US4.4 billion for physician and other fees, $US2.5 billion for
      drugs, $US1.5 billion for nursing home care and $US1.0 billion for home care.
      Office visits, hospital outpatient visits and emergency department visits
      accounted for 17.3% of the direct costs for COPD in the US. When stratified by
      severity, COPD treatment costs strongly correlate with disease severity. The
      American Thoracic Society, the European Respiratory Society and the British
      Thoracic Society have developed guidelines for the pharmacological treatment of
      COPD. However, the guidelines establish inhaled bronchodilators (anticholinergic
      agents and beta 2-adrenergic agonists) as the mainstay of therapy for patients
      with COPD. The guidelines were not based on cost analyses and thus are not a
      priori cost-effective guidelines. Since the publication of these guidelines,
      several new pharmacological products have been approved for use in patients with
      COPD including a combination of an anticholinergic and selective beta 2
      adrenergic agonist [ipratropium/salbutamol (albuterol)] and a long-acting beta 2
      adrenergic agonist (salmeterol). Both products are effective bronchodilators in
      COPD. The purpose of this report is to place these new agents in an updated
      pharmacological guideline scheme, utilising recently published data on clinical
      efficacy as well as pharmacoeconomics. The annualised healthcare costs were
      computed to be $US788/patient/year for the combination ipratropium/salbutamol
      inhaler and $US1059/patient/year for salmeterol (1999 values). Based upon an
      improved understanding of the complexity of COPD, the response of patients to
      newer bronchodilators (given individually or in combination), and recent
      pharmacoeconomic data for COPD treatment, a new treatment algorithm with
      associated costs is proposed. The use of an algorithm, based on medical and
      pharmacoeconomic data, will improve lung function in patients with COPD, improve
      patient satisfaction (e.g. quality of life, dyspnoea) and outcomes (e.g.
      exacerbations). It will also result in a positive effect on healthcare costs.

PMID- 11303414
TI  - Cost effectiveness of emedastine versus levocabastine in the treatment of
      allergic conjunctivitis in 7 European countries.
AB  - OBJECTIVE: To assess the cost effectiveness of emedastine, a new antihistamine,
      versus levocabastine in the treatment of acute allergic conjunctivitis (AAC) in
      Belgium, France, Germany, The Netherlands, Norway, Portugal and Sweden. DESIGN
      AND SETTING: Randomised double-blind multicountry clinical trial followed by
      economic modelling from the treatment provider perspective. PATIENTS: A total of
      221 patients (109 emedastine, 112 levocabastine) with AAC were included. METHODS:
      The clinical trial compared the efficacy and safety of emedastine 0.05% and
      levocabastine 0.05%, both twice daily, for 42 days, using ocular redness,
      itching, days without symptoms and clinical failure as outcome measures. The cost
      of first-line treatment failure, including visits, drugs and laboratory
      examinations, was established in each country from a panel of ophthalmologists
      and general practitioners. Full sensitivity analyses were conducted. RESULTS:
      From day 7 to 42, patients treated with emedastine had less itching (p < 0.001)
      and less redness (p < 0.001). The failure rate was 10% less (p < 0.02) with
      emedastine and patients treated with emedastine had an incremental 8.5 days (p <
      0.01) without symptoms. Emedastine and levocabastine were equally well tolerated.
      In all European countries, the cost of failure was lower with emedastine.
      Emedastine was found to be economically dominant relative to levocabastine, i.e.
      more effective and less expensive, in Belgium, Germany, Portugal and Sweden; in
      France, The Netherlands and Norway the incremental cost was low (less than 1 euro
      per additional symptom-free day). CONCLUSION: Through a model based on a
      randomised clinical trial and cost estimates of treatment failure derived from
      practitioner interviews, emedastine is a cost-effective treatment of AAC.

PMID- 11303415
TI  - Cost of treatment for onychomycosis. Data from a 9-month observational study.
AB  - OBJECTIVES: To estimate component and total costs of treatment and to examine
      differences in cost and cost effectiveness between oral antifungal medication and
      local therapy for patients with toenail onychomycosis. DESIGN: Prospective,
      observational study of patients with onychomycosis who visited dermatologists and
      podiatrists in the US. Physicians provided data on clinical management, disease
      severity, nail improvement and resource utilisation. Patients completed
      questionnaires on resource utilisation and symptoms at base-line, 4 and 9 months.
      To estimate costs, reported utilisation was multiplied by unit costs expressed in
      1997 US dollars ($US) and derived in 2 ways: first, using Medicare fees; and
      second, using standard physician fees. RESULTS: After adjustment for key
      demographic and clinical variables, participants receiving oral medication had
      higher total costs based on standard fees ($US794 vs $US575) and medication costs
      ($US564 vs $US109), lower procedure costs ($US0 vs $US122) and physician visit
      costs ($US200 vs $US330), and greater clinical effectiveness as measured by
      global improvement rating (86 vs 35%) and Toenail Symptom Index (94 vs 49%). For
      participants receiving oral medication, 90% of total costs were incurred during
      the first 4 months of follow-up, whereas for those receiving local therapy, costs
      were more evenly distributed throughout the study period. Incremental cost
      effectiveness analysis showed $US304 to $US491 per additional case improved with
      oral medication over a 9-month timeframe. Extrapolation of these results using 2
      time-points (months 4 and 9) suggested that cost equivalence would be reached 17
      to 21 months following the initiation of treatment. CONCLUSIONS: During 9 months
      of follow-up in patients with toenail onychomycosis, the use of oral antifungal
      medication resulted in superior patient outcomes, but at higher total cost
      compared with local therapy.

PMID- 11303417
TI  - Cost-effectiveness analysis of inhaled zanamivir in the treatment of influenza A
      and B in high-risk patients.
AB  - OBJECTIVE: To evaluate the cost effectiveness of zanamivir 10 mg twice daily for
      5 days in the treatment of influenza in high-risk patients. DESIGN: Bootstrap
      cost-effectiveness analysis incorporating within-trial analysis of pooled patient
      level cost and effect data. SETTING: UK unit costs and utilities applied to high
      risk patients drawn from 6 multinational clinical trials. PATIENTS: A total of
      154 zanamivir and 167 placebo high-risk patients were included in the analysis.
      MAIN OUTCOME MEASURES: Cost per day of normal activities; cost per symptom-free
      day; cost per complication averted; cost per quality-adjusted life-year (QALY).
      RESULTS: The mean benefit was estimated to be 2.5 days [95% confidence interval
      (CI): 0.68 to 4.27] of normal activities gained; 2.0 (95% CI: 0.56 to 3.51)
      symptom-free days; and a 9% reduction in complications (95% CI: 0 to 18%).
      Excluding the effect of rare hospitalisation costs, the cost (1999 values) of
      gaining a day of normal activities was 9.50 Pounds (95% CI: 5 Pounds to 39
      Pounds); cost per symptom-free day was 11.56 Pounds (95% CI: 6 Pounds to 43
      Pounds); cost per complication averted was 262 Pounds (95% CI: 90 Pounds to 1574
      Pounds). Influenza was estimated to reduce utility by 0.883 per day,
      demonstrating the debilitating effect of the disease. Extrapolating a day of
      normal activities to a standard utility measure resulted in a cost per QALY of
      3900 Pounds excluding inpatient costs (7490 Pounds including inpatient costs).
      Cost-effectiveness acceptability curves demonstrated 90% certainty that zanamivir
      would be cost effective at 8000 Pounds per QALY. CONCLUSIONS: Significant health
      benefits can be obtained with zanamivir treatment in high-risk patients. The cost
      per QALY for zanamivir in these patients compares well with that of other
      commonly used pharmacological interventions.

PMID- 11303416
TI  - Cost-benefit analysis of active vaccination campaigns against hepatitis A among
      daycare centre personnel in Israel.
AB  - OBJECTIVE: To evaluate, in economic terms, active vaccination campaigns against
      hepatitis A in comparison with the use of nonspecific immune globulin for the
      prevention of the disease among daycare centre employees in Israel. SETTING:
      Hypothetical analysis of the costs and benefits related to vaccination campaigns
      of workers currently employed in daycare centres in Israel. METHODS: A cost
      benefit analysis was performed, comparing mass and selective active vaccination
      strategies for the daycare centre working force. Direct and indirect costs of
      diagnosis, treatment and immunisation as well as productivity loss were
      considered. A Markov-based model was developed using data from previous
      epidemiological studies and literature. RESULTS: The benefit-to-cost ratios of
      selective and mass active vaccination strategies were 1.50 [net present value
      (NPV) $US606 396] and 0.04 (NPV-$US2.36 million), respectively (2000 values).
      CONCLUSION: Under these study assumptions, the practice of administering
      hepatitis A active vaccine to serologically proven non-immune daycare centre
      workers has a cost-benefit justification, and should be widely considered in
      countries with a similar hepatitis A epidemiology to that in this study.

PMID- 11303419
TI  - Mass. nurses seek to bolt ANA. Vote reflects desire for more activist approach
      than national group has provided.

PMID- 11303418
TI  - Rivastigmine. A pharmacoeconomic review of its use in Alzheimer's disease.
AB  - Alzheimer's disease is associated with a large cost burden, of which
      institutionalised care constitutes a major component. Therefore, the decision to
      move a patient from the community to institutionalised care is associated with a
      significant increase in direct costs. About three-quarters of patients with
      Alzheimer's disease are admitted to a nursing home within 5 years of diagnosis.
      Unpaid or informal caregiver time is another large cost in Alzheimer's disease,
      especially for patients cared for in the community; informal care can account for
      up to three-quarters of healthcare costs in non-institutionalised patients.
      Several cholinesterase inhibitors, of which rivastigmine is one, are available
      for the treatment of patients with mild to moderate Alzheimer's disease. By
      improving cognitive function and slowing the rate of cognitive decline,
      cholinesterase inhibitor therapy may reduce a significant part of the economic
      burden of the disease by delaying the move to institutionalised care. In the
      absence of prospective long term data which focus on pharmacoeconomic end-points,
      modelling techniques have been used to extrapolate clinical data available for
      some cholinesterase inhibitors, including rivastigmine. Four economic analyses,
      based on a single model of cognitive decline, have been performed with
      rivastigmine from the perspective of the provider or society. All show that
      rivastigmine therapy (excluding drug-related costs) is associated with cost
      savings in patients with mild to moderate Alzheimer's disease by delaying the
      time to institutionalisation. If the acquisition cost of the drug was factored
      in, the cost savings completely or partially offset treatment costs. The
      magnitude of the cost savings increased as the time horizon increased (up to 2
      years). The largest savings were realised in patients with mild disease over a 2
      year time-frame, suggesting that treatment should be initiated early from an
      economic viewpoint. Pharmacoeonomic data comparing different cholinesterase
      inhibitors are, as yet, unavailable. CONCLUSION: Pharmacoeconomic analyses, based
      on modelled data excluding drug costs, indicate that rivastigmine completely or
      partially offsets the costs of treatment by delaying cognitive decline and the
      time to institutionalisation in patients with mild to moderate Alzheimer's
      disease. From a societal perspective, cost savings are realised if the drug is
      introduced early in the disease. Additional benefits offered by rivastigmine on
      behavioural symptoms, which may reduce caregiver burden, have yet to be
      investigated from a pharmacoeconomic perspective.

PMID- 11303420
TI  - Going digital. HealthSouth, Oracle plan automated hospital.

PMID- 11303421
TI  - Idaho hospital makes a private decision.

PMID- 11303422
TI  - A costly strategy. Government puts a price tag on charges involving HCA's
      physician deals.

PMID- 11303423
TI  - Small hospital with 'big heart' imperiled. Facility in poor Adirondacks region of
      N.Y. hit by red ink, state restrictions.

PMID- 11303424
TI  - Ethical quandary. Smaller AMA moves slowly on rules for drug firms' influence
      over prescribing.

PMID- 11303425
TI  - Drug giant buys high profile at site.

PMID- 11303426
TI  - Acquisition binge: the sequel. Flush with cash, for-profit chains are once again
      buying and rebuilding hospitals.

PMID- 11303427
TI  - Opening soon. Controversial new med school in Florida is first in the nation
      since 1982.

PMID- 11303428
TI  - Cleveland Clinic plans new medical school.

PMID- 11303429
TI  - Paying a premium. Hospitals face jump in costs for directors and officers'
      insurance coverage.

PMID- 11303430
TI  - HIPAA privacy rule changes likely. Thompson wants to simplify standards and ease
      financial burden.

PMID- 11303431
TI  - AHA calls privacy rule 'unworkable'. Hospitals need more time to prepare; rules
      create barriers to care.

PMID- 11303432
TI  - Ultraviolet light as a topical agent for malignant melanoma and the role of
      sunscreen.

PMID- 11303433
TI  - Children, drugs, and the Food and Drug Administration: studies of pediatric drugs
      are beginning to catch up.

PMID- 11303434
TI  - Dermatologic toxicology in children.

PMID- 11303435
TI  - Beyond poison ivy: understanding allergic contact dermatitis in children.

PMID- 11303436
TI  - The importance of vehicle in pediatric topical therapy.

PMID- 11303437
TI  - New developments in wound care for infants and children.

PMID- 11303438
TI  - The appropriate use of topical antimicrobials and antiseptics in children.

PMID- 11303439
TI  - The safe use of topical corticosteroids in children.

PMID- 11303440
TI  - Resident's column: Use of topical anesthetics in children.

PMID- 11303441
TI  - Washington State system finds Web success through vendor relationship.

PMID- 11303442
TI  - Consumer expectations to reshape providers' Net strategies.

PMID- 11303443
TI  - The other privacy law: preparing for the Gramm-Leach-Bliley Act.

PMID- 11303444
TI  - Visit these IT and "new economy" sites for help keeping up with the
      technical/business world.

PMID- 11303445
TI  - Studies produce mixed portrait of online health consumer.

PMID- 11303446
TI  - The blue blazer.

PMID- 11303447
TI  - From sermon to poem.

PMID- 11303448
TI  - Zebra.

PMID- 11303449
TI  - Farewell to a fallen warrior.
AB  - In the Summer of 1999, Kemp Burleson had what he thought was going to be a rather
      routine annual physical exam. By his own estimate, at 37-years-old he was in
      perfect health. There was no warning of what was to come. At his wife's
      insistence, he asked for a blood test to determine if his cholesterol was
      elevated, as there was a family history of heart disease. Within days, the
      results were in. They were not good. It was not a cholesterol problem. He had
      leukemia and would need a bone marrow transplant to increase his odds for
      survival. In spite of the attempts to extend his life, he lived only several
      months following that initial diagnosis. The following is the eulogy that was
      inspired by our time together in the hospital.

PMID- 11303450
TI  - The Hamilton SPE Evaluation Tool (HSET): is it any good?
AB  - Presents the Hamilton Supervised Pastoral Evaluation Tool (HSET). HSET is a self
      report that evaluates student learning in a basic SPE unit utilizing six areas:
      supervisory relationship, personal growth, professional growth, theological
      reflection, learning context, and overall growth. Reviews statistics involving
      seven regional units consisting of 18 SPE units with 101 students. Utilizes
      methodological, investigator, and data triangulation by drawing on qualitative
      study and CAPPE accreditation review. Discusses strengths and weaknesses of HSET
      and makes recommendations for further use.

PMID- 11303451
TI  - Three puzzles surrounding the persistent non-integration between psychology and
      pastoral counseling.

PMID- 11303452
TI  - Care for the caregiver: effective pastoral support for nursing home staff.
AB  - Notes that the contexts in which caregivers work shape the kinds of relationships
      they develop with those under their care. Suggests that it is possible to map
      these contextual features on a continuum with detached professionalism and
      involved familialism representing the extremes. Claims that nursing home staff
      are more akin to family members in their relationships with residents than are
      other professional caregivers who work in acute care settings. Sketches possible
      implications as to how recognizing and responding to these relational dynamics
      may influence specific modes of care.

PMID- 11303453
TI  - Conversion therapy revisited: parameters and rationale for ethical care.
AB  - Observes that efforts are being made within certain professional counseling
      associations to oppose and prohibit attempts to modify homoerotic feelings and
      behavior on ethical grounds. Outlines several factors that can motivate the
      pursuit of conversion therapy and reviews data that suggest change is a viable
      treatment outcome. Proposes, based on an analysis of research data, an ethical
      framework within which conversion therapy can be legitimately practiced.

PMID- 11303454
TI  - A collaborative pastoral care and counseling supervisory model.
AB  - Presents a collaborative pastoral care and counseling supervisory model based on
      constructivism and attachment theories. Addresses issues concerning cognition,
      learning theory, and anxiety. Identifies the stages in the supervisory process.
      Discusses ways in which cognitive, emotional, and social development are linked
      to attachment theory and places this in the context of supervision in pastoral
      counseling. Reflects on the theological relevance of attachment theory utilizing
      the biblical parable of the prodigal son.

PMID- 11303455
TI  - Prayer and fasting in the halls of Congress: a pastoral approach to lobbying.
AB  - Describes a pastoral model for congressional lobbying and how this became the
      vehicle for a ministry of prayer and fasting supporting debt forgiveness for the
      world's 40 most impoverished nations. Raises questions for the reader concerning
      the need to take risks in doing effective ministry.

PMID- 11303457
TI  - Faith is the key: building a community of caring.

PMID- 11303456
TI  - A White Paper. Professional chaplaincy: its role and importance in healthcare.
AB  - This paper describes the role and significance of spiritual care and is the first
      joint statement on this subject prepared by the five largest healthcare
      chaplaincy organizations in North America representing over 10,000 members. As a
      consensus paper, it presents the perspectives of these bodies on the spiritual
      care they provide for the benefit of individuals, healthcare organizations and
      communities. Throughout this paper, the word spirituality is inclusive of
      religion; spiritual care includes pastoral care. Spiritual caregivers in
      healthcare institutions are often known as chaplains although they may have
      different designations in some settings, i.e. spiritual care providers. The paper
      contains four sections. 1. The Meaning and Practice of Spiritual Care This first
      section describes spirit as a natural dimension of all persons and defines the
      nature of spiritual care. With the basic premise that attention to spirituality
      is intrinsic to healthcare, the paper establishes their relationship and outlines
      the various environments in which it is provided. 2. Who Provides Spiritual Care?
      Professional chaplains provide spiritual care and this section describes their
      education, skills and certification. 3. The Functions and Activities of
      Professional Chaplains This section delineates the typical activities of
      professional chaplains within healthcare settings, focusing on their care of
      persons and their participation in healthcare teams. 4. The Benefits of Spiritual
      Care Provided by Professional Chaplains The materials here describe how
      professional chaplains benefit healthcare patients and their families, staff
      members, employing organizations, and communities.

PMID- 11303458
TI  - Dietary intakes and food habits of adolescents in northern Greece.
AB  - The purpose of this study was to assess the dietary intakes and food habits of
      582 adolescents in Northern Greece. Anthropometric data have been collected for
      all the participating adolescents. The prevalence of obesity as determined by
      both body mass index (BMI) and triceps skinfold thickness (TST) was higher for
      boys than for girls. Furthermore, boys had higher energy and macronutrient
      intakes compared to girls. Of total energy intake, 41% for boys and 43% for girls
      was derived from fat. Energy intake was found adequate whereas fat intake was
      much higher than recommended. A percentage of adolescents also had lower than
      recommended iron, vitamin A, folate and zinc intakes, showing an unbalanced diet.

PMID- 11303459
TI  - Evaluation of nutritive value and functional qualities of sorghum subjected to
      different traditional processing methods.
AB  - Sorghum (Sorghum bicolar L. Moench), a staple food in many parts of the world, is
      underutilised compared to its potential due to inherent problems. A study was
      conducted to evaluate the effect of different traditional processing methods on
      the nutritional and functional qualities of sorghum. The review of literature
      established the main causes of the low level of sorghum utilisation to be low
      nutritional and inferior organoleptic qualities. It was further established that
      traditional processing methods, such as germination and fermentation, can promote
      its utilisation. Three processing methods, namely germination (G), fermentation
      (F), and germination combined with fermentation (GF), were used to prepare feeds
      from two sorghum varieties, Tegemeo and Udo. Evaluation of the feed qualities in
      terms of acceptability, retention, feed efficiency ratio (FER) and protein
      efficiency ratio (PER), using weanling rats was carried out and compared to the
      untreated one which served as control. An element of functional properties was
      assessed in terms of diastatic power (DP). Regarding feed intake, there was no
      significant difference between the feeds. Body retention for Tegemeo variety was
      higher than that for Udo. FER ranged from 0.019 +/- 0.015 to 0.095 +/- 0.015, PER
      ranged from 0.113 +/- 0.089 to 0.703 +/- 0.111 and diastatic power from 15.99 +/-
      1.20 to 114.58 +/- 0.95. In all the three cases, germinated feeds had the highest
      values and were therefore considered of higher nutritional value. It was
      therefore concluded that germination was superior to the other processing methods
      in improving the nutritional and functional qualities of sorghum.

PMID- 11303460
TI  - The association between nutrition knowledge and eating behavior in male and
      female adolescents in the US.
AB  - Some factors that could influence adolescent eating behavior include: peer
      influences, nutrition knowledge and beliefs, mass media, and parental dietary
      habits. The purpose of this study was to examine the correlation of nutrition
      knowledge and eating behavior of a sample of middle school children. The
      participants were 532 students in the sixth, seventh, and eighth grades between
      the ages of 11 and 13 from Shawnee Middle School in Lima, Ohio. The students were
      asked to answer a questionnaire, CANKAP (Comprehensive Assessment of Nutrition
      Knowledge, Attitudes, and Practices), which measured their nutrition knowledge
      and eating behavior. The CANKAP questionnaire consisted of 30 questions for sixth
      grade students and 35 questions for seventh and eighth-grade students. Also, the
      participants were asked to identify their gender. The findings indicated that
      females had higher mean nutrition knowledge scores than boys in the seventh and
      eighth grades. There was no correlation between nutrition knowledge and food
      choices in the sixth-grade male or female students. However, there was a
      correlation between nutrition knowledge and food choices for girls in the seventh
      and eighth grades. In addition there was a correlation between nutrition
      knowledge and food choices for boys in the seventh and eighth grades.

PMID- 11303461
TI  - A home-based method to reduce phytate content and increase zinc bioavailability
      in maize-based complementary diets.
AB  - This study aimed to develop and assess the feasibility of a home-based method to
      reduce the phytate content of maize and improve zinc bioavailability from maize
      based complementary diets in rural Malawi. A method of extracting phytate through
      the soaking of pounded maize was developed, and found to reduce phytate content
      to 49% of unrefined maize. An educational program was used to teach the
      processing method to mothers of children receiving complementary foods in rural
      Malawian communities. Samples of maize flour prepared by this process by
      participants were collected and analysed for phytate and zinc content. Of these,
      70% of samples were found to be adequately prepared; mean phytate content of
      these samples was 48% of unprocessed, unrefined maize flour controls. Most
      participants found the cooked product to have an acceptable taste (99%) and
      texture (68%), and felt the processing method took little or no extra time (86%)
      and was culturally acceptable (96%). The phytate and zinc content of the
      processed maize flour samples analysed from community prepared samples was
      substituted into the dietary analysis of complementary foods for 9- to 11-month
      old children (n = 31). The bioavailability of zinc from the complementary diet
      would predict an increase from low (24%) to moderate (33%) levels.

PMID- 11303462
TI  - Antioxidant capacity of lycopene-containing foods.
AB  - Increased consumption of tomatoes and tomato products has been associated with
      decreased cancer risks. One fat-soluble compound identified in tomatoes which may
      be responsible for this association is lycopene. There may, however, be other
      antioxidants present in tomato-based foods, and total antioxidant capacity may be
      another way to rate the health benefits of these foods. In this work, we examined
      the Trolox-equivalent antioxidant capacity (TEAC) of aqueous and organic extracts
      of lycopene-containing foods: ketchup, fresh tomatoes, tomato paste, tomato
      sauce, tomato soup, tomato juice, vegetable juice, canned tomatoes and
      watermelon. Antioxidant activity in these food extracts was greater in the
      aqueous versus organic fractions, except for watermelon and tomato sauce where
      the levels were similar in the two fractions. Lycopene levels in the food samples
      tested, however, were relatively greater in the organic fractions, with the
      exception of the two juices, which had similar levels in the two fractions, and
      two highly concentrated tomato products, tomato paste and ketchup, which had
      relatively higher lycopene levels in the aqueous fractions. The foods with the
      highest antioxidant capacity per serving overall (tomato soup was highest) did
      not have the highest lycopene levels. This indicates that it may be important to
      consume a variety of tomato-containing products in order to obtain the largest
      variety of dietary antioxidants possible.

PMID- 11303464
TI  - Assessment of villagers' perceptions towards nutrition communication in rural
      Nepal.
AB  - This article examines the perceptions of villagers of Nepal towards effective
      modes of nutrition communication affecting their nutritional health. Based on the
      villagers' experience of the nutrition communication used in various vitamin A
      projects surveyed in three districts of Nepal, a majority of the villagers
      strongly believe that a nutrition project cannot be effective in achieving its
      goals unless the local villagers are consulted during the process (defined to
      include design, development, implementation, and evaluation). They also believed
      that, among other modes of communication, a group discussion might be very
      effective in village nutrition communication. Similarly, based on the survey data
      analysis, it was found that the use of multiple media had a strong positive
      impact on the villagers' familiarity with and participation in the vitamin A
      projects surveyed. However, there was not any indication that such impact had a
      significant positive relationship with the reported level of knowledge of food
      items promoted by the vitamin A projects. Likewise, there was no suggestion of
      any strong relationship between the reported level of knowledge and the intake of
      food items promoted by the projects surveyed.

PMID- 11303463
TI  - Comparison of a self-administered quantitative food amount frequency
      questionnaire with 4-day estimated food records.
AB  - Our objective was to assess the relative validity of a self-administered food
      amount frequency questionnaire (FAQ), using 4-day estimated food records (FRs) as
      a reference method, for use in a subsequent clinical study of patients undergoing
      heart surgery. Thirty healthy subjects (19 males, 11 females), aged 45-75 years,
      were randomly recruited from patient lists generated by two local GP practices in
      Oxford. Complete data from the FAQ and FR, administered twice 6 months apart,
      were available for 25 subjects (16 males, 9 females). For absolute nutrient
      values, intakes of protein, CHO, total fat, PUFA, thiamin, iron, dietary fibre
      and alcohol were not significantly different between the FAQ and FR, and
      Pearson's correlation coefficients ranged from 0.28 for protein to 0.88 for total
      fat. Estimates from the FAQ were within +/- 10% of the estimates produced by the
      FR for two-thirds of nutrients. When nutrients were expressed as a percentage of
      total energy intake, no statistically significant differences were observed for
      any nutrient between the two methods, and correlations ranged from 0.32 for
      protein to 0.80 for SFA. In conclusion, the broad dietary patterns obtained by
      the two methods of assessment were comparable. This simple and inexpensive FAQ
      can be used to usefully estimate group intakes for a variety of nutrients in the
      study of patients undergoing heart surgery.

PMID- 11303465
TI  - A method for in vitro determination of calcium, iron and zinc availability from
      first-age infant formula and human milk.
AB  - A method for in vitro determination of available calcium, iron and zinc content
      from infant food after digestion was evaluated. This method introduced an
      intraluminal digestive phase, adapted to the gastrointestinal conditions of
      infants younger than 6 months of age, prior to continuous flow dialysis of the
      resultant gastric digest. Precautions handling the method were discussed and
      enzymatic parameters were defined. Ruggedness of the method was determined from
      the availability of calcium, iron and zinc at different gastrointestinal
      conditions. Availability of all three elements was higher at gastric pH of 2
      (20.0 +/- 1.1% for calcium, 4.06 +/- 0.66% for iron and 17.5 +/- 1.3% for zinc),
      than from the normal procedure (pH 4) (15.6 +/- 1.2% for calcium, 1.18 +/- 0.26%
      for iron and 8.2 +/- 0.9% for zinc). At pH 5, however, calcium availability
      appeared to be lower (11.7 +/- 1.0%) (P < 0.05). The intestinal pH also had a
      major influence on the availability. At low intestinal pH (5.5), availability was
      40.5 +/- 2.3% for calcium, 3.01 +/- 0.58% for iron and 26.8 +/- 1.8% for zinc,
      which was higher compared with the normal procedure (P < 0.05). Moreover, other
      factors, such as digestion time, mixing and filtration pressure, also affected
      the availability. Recovery tests yielded mean values of 94 +/- 3% for calcium,
      109 +/- 9% for iron and 106 +/- 4% for zinc. Mean intra- and inter-batch
      precision of the availability procedure was 4.1 CV% and 6.6 CV% for calcium, 14.5
      CV% and 19.2 CV% for iron, and 4.0 CV% and 13.6 CV% for zinc. The method provides
      adequate accuracy, acceptable precision and good recovery. It offers the
      advantage of being simple, rapid and inexpensive, since it takes only 1 day to
      run the whole availability procedure (including four replicates per sample), and
      the low costs of the dialysis equipment. It can therefore be considered as
      suitable for predicting the availability of essential elements from foods used
      during the first months of infancy.

PMID- 11303466
TI  - Splanchnic amino acid balance is affected by moderate variations of dietary
      protein in the developing Zucker rat.
AB  - This study attempted to determine the influence of moderate chronic variations in
      dietary protein intake, on splanchnic amino acid balances. Two series of 30-day
      old male lean (Fa/?) Zucker rats were fed ad libitum for 30 days with either a
      standard diet (reference diet: RD), a high-protein diet (HP) (35%) or a low
      protein diet (LP) (9%). After 30 days of dietary treatment, blood was withdrawn
      from hepatic vein, portal vein and arterial aorta in one set of rats. In another
      series the splanchnic organ blood flows were determined using fluorescent
      microspheres. From the individual amino acid concentration in each sample and the
      blood flows, we calculated the intestinal and hepatic balances. There were no
      significant differences in the hepatic arterial, portal or supra-hepatic flows
      induced by dietary protein content. The RD group showed a marked intestinal
      uptake of Gln and Cit and a net release of Pro, Ala and Gly. The LP group showed
      the same pattern, with increased release of Ala and Gly. In contrast to this
      limited amino acid release, the HP group showed a generalized net release of
      amino acids from the intestine. The RD group only show a net Gln release from the
      liver. Conversely, the HP group showed net uptake of Gln, Pro, Ala, Tyr and Lys,
      and the LP group took up Gly and Ala and released Asn, Gln and Cit. Our results
      indicate that growing Zucker rats respond to long-term moderate changes in the
      protein intake, diminishing the growth pattern only in the LP group, but not in
      the HP group. In spite of the limited amino acid supply, the LP group followed a
      similar pattern of intestinal balance for Ala, Gln, Pro, Gly and Cit, as showed
      by the RD group. On the other hand, excess of dietary amino acids in the HP group
      seems to promote a lower utilization of Gln by intestine probably due to an
      increased release of Ala instead of Gln from peripheral tissues.

PMID- 11303467
TI  - Energy expenditure of rats subjected to long-term food restriction.
AB  - Food restriction, even when expressed per unit of metabolic mass, leads to energy
      conservation as seen by decreased oxygen consumption. The objective of the
      present study was to verify whether the energy conservation mechanism reduces
      energy expenditure for as long as food restriction lasts or whether a return to
      basal level may occur without realimentation, mainly in mildly food-restricted
      rats. Wistar rats were brought to the laboratory on weaning. They were then
      assigned to control group that received ad libitum food intake, R10 and R20
      groups that received 90 and 80%, respectively, of the food eaten by control group
      and RM group that received an amount of food enough only to keep body weight. The
      food restriction period lasted for 3 months and was followed by another month
      during which all groups received ad libitum food intake. The results showed that
      even in animals subjected to mild food restriction (10%) there was a sustained
      decrease in oxygen consumption that lasted until refeeding of the animals. The
      results led to the conclusion that the energy conservation mechanism is active
      from little food restriction until more stronger levels of restriction, in a
      proportional manner, and the decreased energy expenditure is maintained during
      the whole food restriction period.

PMID- 11303468
TI  - Speaking the language of finance.
AB  - Nursing leadership skills have changed dramatically in a short period of time.
      Just being able to cover the schedule and ensure adequate orientation for new
      employees are not enough in today's health care environment. This article
      outlines steps to ensure adequate staffing levels, assess productivity, and
      justify the operational supplies and capital equipment necessary for effective
      patient care. It also outlines steps nursing leaders can take to market their
      programs and services.

PMID- 11303469
TI  - Uterine artery embolization.
AB  - The use of uterine artery embolization is a new approach in the treatment of
      uterine fibroids. Embolization is a technique in which blood vessels that supply
      nutrients and oxygen to fibroids are blocked. This blockage causes the fibroid
      muscle cells to degenerate and form scar tissue, thus shrinking the fibroid.
      Usually the fibroid no longer causes symptoms. This minimally invasive procedure
      involves an overnight hospital stay and results in a reduction of fibroid
      symptoms. Most women notice the greatest improvement in the first eight weeks.
      This procedure has been performed only since 1990 and, therefore, long-term
      results are unknown.

PMID- 11303470
TI  - Use of a deployable medical system during the remodeling of an OR.
AB  - How can a five-suite OR be remodeled while providing continuous, cost-effective
      surgical procedures without decreasing workload? Such a question was met with an
      innovative answer at the Veterans Affairs Medical Center, Fresno, Calif.
      Deployable Medical System units were selected to provide surgical support. The
      decision-making process, challenges, and surgical capabilities will be reviewed.
      Methods of quality control are presented, and cost benefits are described.

PMID- 11303471
TI  - The presence of sales representatives in the OR.

PMID- 11303472
TI  - Understanding life experiences through a phenomenological approach to research.

PMID- 11303473
TI  - State laws and regulations for office-based surgery.

PMID- 11303474
TI  - Better stroke prevention.

PMID- 11303475
TI  - Is it true that saunas are dangerous for some people?

PMID- 11303476
TI  - What is sepsis, and why is it life threatening?

PMID- 11303477
TI  - Making sense of PSA.

PMID- 11303478
TI  - Fruits, veggies, and breast cancer: time to toss away five-a-day?

PMID- 11303479
TI  - Human genome decoded--now what?

PMID- 11303480
TI  - Tests allay bee-sting and peanut fears.

PMID- 11303481
TI  - Hold the cheese!

PMID- 11303482
TI  - Ratio may foretell risk of heart disease.

PMID- 11303483
TI  - Never too old for a new knee or hip.

PMID- 11303484
TI  - Iron: too much or too little?

PMID- 11303485
TI  - HPV test clarifies ambiguous Pap results.

PMID- 11303486
TI  - Diet drugs often used inappropriately.

PMID- 11303487
TI  - Rapid aggressive soft-tissue necrosis after beetle bite can be treated by radical
      necrectomy and vacuum suction-assisted closure.
AB  - BACKGROUND: The substance cantharidin, which is produced by a type of beetle,
      rapidly penetrates the epidermis and can cause severe toxicities such as skin
      necrosis. Optimal treatment for necrotic beetle bites has not been well defined.
      Conservative management has been advocated but the hospital stays are long and
      long-term morbidity may result, especially in multimorbid patients. OBJECTIVE:
      The value of aggressive surgical management of such necrotizing diseases using
      newly developed surgical tools is compared to the traditional more conservative
      approach. RESULTS: We present the case of a multimorbid 60-year-old man with a
      rapidly progressive necrosis of the medial thigh (measuring 30 X 15 cm), acquired
      during a stay in Western Africa after being bitten by a beetle of the species
      Cantharide. The patient was treated with radical surgical debridement and
      continuous elimination of the wound fluid by permanent computer-controlled
      negative pressure with a vacuum-assisted wound-closure device. This led to the
      sudden relief of both local and systemic symptoms and allowed extremely early
      wound closure. CONCLUSIONS: Comparing literature data with the course of this
      combined treatment, we strongly suggest an early aggressive management with
      complete radical excision of necrotic tissue, conditioning of the wound bed by
      temporary suction-assisted vacuum closure and subsequent skin grafting with
      continued vacuum application. This treatment leads to immediate relief of pain
      and enhanced healing of this lesion even in the condition of immunosuppression in
      the elderly.

PMID- 11303488
TI  - Weekly supplementation with iron and vitamin A during pregnancy increases
      hemoglobin concentration but decreases serum ferritin concentration in Indonesian
      pregnant women.
AB  - We investigated whether weekly iron supplementation was as effective as the
      national daily iron supplementation program in Indonesia in improving iron status
      at near term in pregnancy. In addition, we examined whether weekly vitamin A and
      iron supplementation was more efficacious than weekly supplementation with iron
      alone. One group of pregnant women (n = 122)was supplemented weekly with iron
      (120 mg Fe as FeSO4) and folic acid (500 microg); another group (n = 121)
      received the same amount of iron and folic acid plus vitamin A [4800 retinol
      equivalents (RE)]. A third ("daily") group (n = 123), participating in the
      national iron plus folic acid supplementation program, was also recruited. Data
      on subjects with complete biochemical data are reported (n = 190). At near term,
      hemoglobin concentrations increased, whereas serum ferritin concentrations
      decreased significantly in the weekly vitamin A and iron group, suggesting that
      vitamin A improved utilization of iron for hematopoiesis. Iron status in the
      weekly iron group was not different from that of the "daily" group. However, iron
      status decreased with daily supplementation if <50 iron tablets were ingested.
      Serum transferrin receptor concentrations increased in all groups (P < 0.01).
      Serum retinol concentrations were maintained in the weekly vitamin A and iron
      group, but decreased in the other two groups (P < 0.01). Thus, delivery of iron
      supplements on a weekly basis can be as effective as ona daily basis if
      compliance can be ensured. Addition of vitamin A to the supplement improved
      hemoglobin concentration.

PMID- 11303489
TI  - Increase in serum beta-carotene following dark green leafy vegetable
      supplementation in Mebendazole-treated school children in Bangladesh.
AB  - OBJECTIVE: To study the effect of consumption of dark green leafy vegetables
      (DGLV) and sweet pumpkin on serum beta-carotene and retinol concentrations in
      children treated for Ascaris lumbricoides. DESIGN: Experimental study with a
      randomised design. SUBJECTS: A total of 110 primary school children aged 8-12 y
      in northwestern Bangladesh. INTERVENTIONS: All children were de-wormed and 2
      weeks later randomly assigned to one of three groups to receive for 6 days per
      week, for 6 weeks, one complete meal containing either: (1) 4.4 mg beta-carotene
      from DGLV (n=37, after 18 dropouts); (2) 1.5 mg beta-carotene from sweet pumpkin
      (n=36, 18 dropouts); or (3) vegetables containing virtually no beta-carotene
      (control) (n = 37, 18 dropouts). RESULTS: Significant increases (P < 0.001) in
      mean serum beta-carotene concentrations were seen in all three study groups, with
      a statistically higher increase (micromol/l) in the DGLV group (0.44; 95%
      confidence interval (CI) 0.32, 0.55) compared to the control group (0.20; 95% CI
      0.14, 0.26; P = 0.002). The increase in serum retinol (micromol/l) was
      statistically significant (P=0.04) only in the DGLV group (mean 0.066; 95% CI
      0.002, 0.13), but this increase was not different from the increase in the
      control group. CONCLUSION: In children successfully treated for Ascaris
      lumbricoides, a substantial increase in serum beta-carotene was seen after
      feeding with a moderately high cumulative dose of DGLV for 6 weeks.

PMID- 11303490
TI  - Dose-response relationship between fat ingestion and oxidation: quantitative
      estimation using whole-body calorimetry and 13C isotope ratio mass spectrometry.
AB  - OBJECTIVE: To determine dose-dependent relationship between ingested fat and its
      oxidation in the immediate post-prandial period in humans. DESIGN: Subjects were
      randomly selected for the study at the Dunn Clinical Nutrition Centre, Cambridge,
      UK. Subjects ingested naturally enriched 13C corn-oil doses (range 20-140g) in a
      whole-body indirect calorimeter, and were studied for 8 h. Ingested fat oxidation
      was estimated from the subject's breath 13C enrichment and total carbon dioxide
      production. Total fat and carbohydrate oxidation were estimated from non-protein
      oxygen and carbon dioxide exchanges. Endogenous fat oxidation was estimated as
      the difference between total fat and ingested fat oxidation. RESULTS: The amount
      of fat dose oxidized was nonlinearly related to the amount ingested. On average,
      25.6+/-2.7% of the mean fat dose was oxidized. A significant (r = - 0.72, P <
      0.001) inverse correlation was found between the amount of fat dose and the
      proportion oxidized. Endogenous carbohydrate oxidation was negatively and
      significantly correlated to fat dose oxidized (r= -0.61, P < 0.01), but it was
      not correlated to endogenous fat oxidation. CONCLUSIONS: There was a nonlinear
      relationship between amount of fat dose and its quantity that was oxidized in the
      immediate post-prandial period. The inverse relationship between the size of the
      fat load and the proportion that was oxidized post-prandially implies increased
      dietary fat storage beyond about 50 g in a normal resting adult. This has
      important implications for 13CO2-based studies.

PMID- 11303491
TI  - Effect of altering the variety of sensorially distinct foods, of the same
      macronutrient content, on food intake and body weight in men.
AB  - OBJECTIVE: To examine the effect of increasing the variety of sensorially
      distinct but nutritionally identical foods on appetite, food intake and body
      weight, over 7 days, in men. DESIGN: Six younger, lean men (mean (s.d.) age 27.0
      (2.9) y; weight 74.7 (3.9) kg; height 1.78 (0.03) m; body mass index (BMI) 23.6
      (1.1) kg/m2) and six older, overweight men (mean (s.d.) age 39.7 (2.9) y; weight
      89.2 (4.4) kg; height 1.78 (0.04) m; BMI 28.1 (0.5) kg/m2) were each studied
      three times during a 9 day protocol, whilst resident in the Human Nutrition Unit.
      On days 1-2, subjects consumed a medium fat (MF) maintenance diet (40% fat, 13%
      protein and 47% carbohydrate by energy) calculated at 1.6 x resting metabolic
      rate (RMR). On days 3-9 subjects had ad libitum access to MF foods (550 kJ/100 g)
      with every item the same macronutrient composition and energy density. Subjects
      had continuous ad libitum access to 5, 10 or 15 food items per day on the low
      variety (LV), medium-variety (MV) and high-variety (HV) treatments, respectively.
      The order of treatments was randomized across subjects. Subjective hunger was
      tracked hourly during waking hours using visual analogue scales (VAS). Body
      weight (as a proxy of changes in energy balance) was measured before eating and
      after voiding, each morning. RESULTS: Food and energy intake of the 12 men
      increased as the variety of foods increased, giving mean energy intakes of 10.13,
      11.00 and 11.89 MJ/day on the LV, MV and HV treatments, respectively (F(2,20) =
      10.32; P < 0.001). This effect was ascribable almost entirely to the lean men.
      Energy intake amounted to 1.57, 1.76 and 1.97 x RMR in the lean men and 1.33,
      1.40 and 1.45 x RMR, for the overweight men on the LV, MV and HV diets,
      respectively. Weight changes amounted to -0.16, -0.28 and + 0.43 kg (lean) -1.03
      and -1.52 kg and -0.66 kg (overweight), on the LV, MV and HV diets, respectively.
      The overweight men may have constrained their energy intake relative to expected
      requirements. This may have been due to a congnitive effect or an age effect.
      There was no significant group or diet effect on subjectively rated hunger.
      CONCLUSIONS: These data suggest that increasing the variety of sensorially
      distinct foods that are virtually identical in composition can increase food and
      energy intake and in the short to medium term can alter energy balance.

PMID- 11303492
TI  - Seasonal variations of antioxidant imbalance in Cuban healthy men.
AB  - OBJECTIVE: To determine the antioxidant imbalance in healthy Cuban men 2y after
      the end of the epidemic neuropathy (50 862 cases from 1991 to 1993) and to
      evaluate its change over 1 y. DESIGN: Prospective study. SETTING: La Lisa health
      centres (Havana, Cuba). SUBJECTS: One-hundred and ninety-nine healthy middle-aged
      men were selected and 106 completed the study. Subjects were studied at 3 month
      intervals over 1 year. INTERVENTIONS: No invervention. MAIN OUTCOME MEASURES: An
      assessment of dietary intake and the determination of blood lipid peroxides
      (TBARS), glutathione, diglutathione, glutathione peroxidase, superoxide
      dismutase, vitamin E, carotenoids, copper, zinc and selenium were performed at
      each period. RESULTS: While dietary zinc, vitamins C and E, carotenoids and fat
      dietary intakes and blood concentrations were low for adult men compared to
      international reference ranges, serum TBARS concentrations were high at every
      period. Some significant seasonal variations were observed. The lowest
      carotenoids (P < 0.002) and vitamin C(P = 0.0001) intakes, serum beta-carotene (P
      = 0.0001) and lutein/zeaxanthin (P < 0.05) concentrations, and the highest blood
      TBARS (P = 0.0001) and diglutathione (P < 0.001) concentrations were observed at
      the end of the rainy season (October). This period seemed to pose the greatest
      risk of antioxidant imbalance. CONCLUSIONS: Cuban men still represent a
      vulnerable population in terms of antioxidant imbalance. A national program of
      vegetable growing and increase in fruit and vegetable consumption is now
      evaluated in Cuba.

PMID- 11303493
TI  - Associations between dietary intakes and blood cholesterol concentrations at 31
      months.
AB  - OBJECTIVE: The initial stages of atherosclerosis have been shown to occur in
      children as young as 3. Elevated total and LDL cholesterol concentrations and low
      HDL concentrations are a well-established risk factor for atherosclerosis. The
      objective of this study was to investigate the dietary determinants of blood
      lipid concentrations at 31 months of age. SUBJECTS: A randomly selected group of
      children (214 boys, 175 girls) in south-west England forming part of the Avon
      Longitudinal Study of Pregnancy and Childhood (ALSPAC) cohort. DESIGN: Three-day
      dietary records were obtained at 18 months. At 31 months a non-fasting blood
      sample was taken and analysed for total and HDL cholesterol and triglyceride, and
      measures of height and weight were taken. RESULTS: Among boys, total cholesterol
      concentrations were positively associated with the intake of total fat (r=0.209,
      P=0.002) and saturated fatty acids (r=0.211, P=0.002). Among girls, HDLC was
      positively associated with energy intake (r=0.204, P=0.018), and negatively
      associated with intakes of polyunsaturated fat, saturated fat and sugar in
      multivariate analysis. There were no associations between the intakes of non
      starch polysaccharides (fibre) or dietary cholesterol and total or HDL
      cholesterol concentrations in either sex. Among boys, higher intakes of breakfast
      cereals were associated with lower total cholesterol (r=-0.187, P=0.008). Among
      girls, higher intakes of biscuits and meat and meat products were associated with
      higher HDLC concentrations. CONCLUSIONS: These data suggest that the dietary
      determinants of blood lipid concentrations differ between boys and girls.
      Reducing saturated fat intake in boys would be likely to lead to an improvement
      in blood lipid profiles. In this study there is no evidence to suggest that an
      increase in the intake of polyunsaturated fat by pre-school children would result
      in improved blood lipid profiles.

PMID- 11303494
TI  - Relationship between stunting in infancy and growth and fat distribution during
      adolescence in Senegalese girls.
AB  - OBJECTIVE: To study the long-term impact of stunting during infancy on
      maturation, growth and fat distribution in adolescence. DESIGN: A cohort of 406
      Senegalese adolescent girls of rural origin underwent clinical and growth
      assessments every year from 1995 to 1999. SUBJECTS: Mean coverage rate was 82% at
      each round. Adolescent girls were 11.4+/-0.5 y of age in 1995 and 15.5+/-0.5 y of
      age in 1999. Their growth status during infancy was known. About 20% of the girls
      had a height-age (H-age) below -2 Z-scores (chronic malnutrition or stunting)
      when they were 6-18 months of age. As adolescents, the girls were divided into
      two groups on the basis of H-age: those stunted and those non-stunted during
      infancy. MEASUREMENTS: Sexual maturation was assessed by stage of breast
      development and menarche. Height, body mass, sitting height, bi-iliac and bi
      acromial diameters, and six skinfolds were measured. RESULTS: Differences in
      sexual maturation between previously stunted and non-stunted girls were not
      significant. Girls stunted at infancy caught up in body weight and subcutaneous
      fat mass during puberty, but they did not catch up on stature, sitting height or
      skeletal breadths (bi-acromial and bi-iliac diameters) until the final
      observation in 1999. Stunted girls did not have less subcutaneous fat (sum of six
      skinfolds) or a lower BMI. Regional variation in subcutaneous fat distribution (Z
      score profile) indicated greater accretion at the biceps and subscapular sites in
      stunted compared to the non-stunted girls. Regional fat distribution was also
      assessed by principal component analysis (PCA) performed on the residuals of the
      six skinfolds measured during the final round (1999). PCA identified three
      components. Stunted and non-stunted girls were similar for the first (trunk
      extremity contrast) and second (anterior-posterior contrast) components. However,
      there was a difference for the third component: stunted girls tended to
      accumulate more subcutaneous fat on the upper part of the body (trunk or arms)
      than non-stunted girls. CONCLUSION: Stunted Senegalese girls have a potential for
      catching up in growth during puberty. The greater accumulation of subcutaneous
      fat on the upper body in stunted girls may be a consequence of complex hormonal
      adjustments at the onset of puberty.

PMID- 11303495
TI  - The occurrence of trans-18:1 isomers in plasma lipids classes in humans.
AB  - OBJECTIVE: The aim of this study was to examine the distribution of trans fatty
      acids (TFA) in plasma lipid classes and the relationship with dietary intake of
      TFA. DESIGN: After a 2 week baseline (habitual) diet, all subjects consumed a
      moderate fat (MF) diet for 3 weeks with the fat being derived mainly from
      margarine and the rest from lean beef, and then a very low fat (VLF) diet for 3
      weeks with the TFA being derived only from the lean beef. Blood samples were
      collected 2 days prior to the end and also on the last day of each dietary
      period. SETTING: Deakin Institute of Human Nutrition, Deakin University, Geelong,
      Australia. SUBJECTS: Ten free-living mildly hypercholesterolaemic subjects aged
      22-66 were recruited in Geelong. OUTCOME MEASURES: TFA intake was calculated from
      analyses of Australian margarines, butter, lean meat and animal fat. The TFA in
      plasma lipid fractions were separated by AgNO3 thin-layer chromatography and
      quantitated by capillary gas-liquid chromatography using internal standards.
      RESULTS: The phospholipid (PL) fraction contained more than 60% of the trans-18:1
      isomers in the plasma lipids in all subjects. On the baseline diet, the
      predominant positional isomer of trans-18:1 in PL was delta11, whereas in the
      other lipid classes it was the delta9 isomer. The concentration of the delta9
      isomer increased on the MF diet, particularly in the PL fraction, while the
      concentration of the delta11 isomer decreased in all fractions. On the VLF diet,
      the total TFA level decreased by approximately 50%, mainly due to decreases in
      the TFA isomers in the PL and TG fractions. Changes in plasma total and PL TFA,
      PL delta9, delta10 and delta11 were strongly correlated with dietary TFA intake
      (P < 0.0001). There were also significant association between dietary TFA intake
      and PL delta12 (P = 0.003), triacylglycerol delta9 (P=0.009), delta11 (P=0.0005),
      total triacylglycerol (P=0.023) and free fatty acid TFA (P = 0.042). CONCLUSIONS:
      The results suggest that the measurement of trans-18:1 in plasma PL and TAG, and
      plasma total TFA could be used to estimate the intake of TFA.

PMID- 11303496
TI  - The MIBG tarot: is it possible to predict the efficacy of beta-blockers in
      congestive heart failure?

PMID- 11303497
TI  - A low maximum inspiratory pressure is not the same as respiratory muscle
      weakness.

PMID- 11303498
TI  - Reversible delirium during opiod switching from transdermal fentanyl to
      methadone.

PMID- 11303499
TI  - Dismantling the Cryptococcus coat.

PMID- 11303500
TI  - Pro-inflammatory programmed cell death.

PMID- 11303501
TI  - New viruses for the new millennium.

PMID- 11303502
TI  - Bacteriophage-bacteriophage interactions in the evolution of pathogenic bacteria.
AB  - Many bacteriophages carry virulence genes encoding proteins that play a major
      role in bacterial pathogenesis. Recently, investigators have identified
      bacteriophage-bacteriophage interactions in the bacterial host cell that also
      contribute significantly to the virulence of bacterial pathogens. The
      relationships between the bacteriophages pertain to one bacteriophage providing a
      helper function for another, unrelated bacteriophage in the host cell.
      Accordingly, these interactions can involve the mobilization of bacteriophage DNA
      by another bacteriophage, for example in Escherichia coli, Vibrio coli and
      Staphylococcus aureus; the host receptor for one bacteriophage being encoded by
      another, as found in V. cholerae; and the presence of one bacteriophage
      potentiating the virulence properties of another bacteriophage, as found in V.
      cholerae and Salmonella enterica.

PMID- 11303503
TI  - Aquaporin and its function in boron uptake.

PMID- 11303508
TI  - Arabidopsis mutants and other model systems in plant physiological ecology.

PMID- 11303509
TI  - Submicroscopic subtelomeric 1qter deletions: a recognisable     phenotype?

PMID- 11303510
TI  - Pure partial 7p trisomy including the    TWIST, HOXA, and GLI3 genes.

PMID- 11303511
TI  - Suggestive linkage of situs inversus    and other left-right axis anomalies to   
      chromosome 6p.

PMID- 11303512
TI  - Founder effect in multiple endocrine    neoplasia type 1 (MEN 1) in Finland.

PMID- 11303513
TI  - Familial non-medullary thyroid cancer    in Iceland.

PMID- 11303514
TI  - Sulphate transporter gene mutations    in apparently isolated club foot.

PMID- 11303515
TI  - Development and application of    linkage analysis in genetic diagnosis of   
      familial hypertrophic cardiomyopathy.

PMID- 11303517
TI  - Analysis of the entire coding region of    the cystic fibrosis transmembrane   
      regulator gene in neonatal    hypertrypsinaemia with normal sweat    test.

PMID- 11303518
TI  - A heterozygous endothelin 3 mutation    in Waardenburg-Hirschsprung    disease:
      is there a dosage effect of    EDN3/EDNRB gene mutations on    neurocristopathy
      phenotypes?

PMID- 11303516
TI  - Genetic heterogeneity and exclusion    of a modifying locus at 17p11.2-p11.1   
      in Finnish families with van der Woude    syndrome.

PMID- 11303519
TI  - The small patella syndrome:    description of five cases from three    families
      and examination of possible    allelism with familial patella    aplasia
      hypoplasia and nail-patella    syndrome.

PMID- 11303520
TI  - Uniparental isodisomy for paternal 2p    and maternal 2q in a phenotypically   
      normal female with two    isochromosomes, i(2p) and i(2q).

PMID- 11303521
TI  - Crystallization and characterization of Pumilo: a novel RNA binding protein.
AB  - Axis determination in early Drosophila embryos is controlled, in part, by
      regulation of translation of mRNAs transcribed in maternal cells during
      oogenesis. The Pumilio protein is essential in posterior determination, binding
      to hunchback mRNA in complex with Nanos to suppress hunchback translation. In
      order to understand the structural basis of RNA binding, Nanos recruitment, and
      translational control, we have crystallized a domain of the Drosophila Pumilio
      protein that binds RNA. The crystals belong to the space group P6(3) with unit
      cell dimensions of a = b = 94.5 A, c = 228.9 A, alpha = beta = 90 degrees, gamma
      = 120 degrees and diffract to 2.6 A with synchrotron radiation. We show that the
      purified protein actively binds RNA and is likely to have a novel RNA binding
      fold due to a very high content of alpha-helical secondary structure.

PMID- 11303522
TI  - Coordination between arm and leg movements during locomotion.
AB  - To evaluate the contrasting dynamical and biomechanical interpretations of the
      2:1 frequency coordination between arm and leg movements that occurs at low
      walking velocities and the 1:1 frequency coordination that occurs at higher
      walking velocities, the authors conducted an experiment in which they quantified
      the effect of walking velocity on the stability of the frequency and phase
      coordination between the individual limb movements. Spectral analyses revealed
      the presence of 2:1 frequency coordination as a constant feature of the data in
      only 3 out of 8 participants at walking velocities ranging from 1.0 to 2.0 km/h,
      in spite of the fact that the eigenfrequencies of the arms were rather similar
      across participants. The degree of interlimb coupling, as indexed by weighted
      coherence and variability of relative phase, was lower for the arm movements and
      for ipsilateral and diagonal combinations of arm and leg movements than for the
      leg movements. Furthermore, the coupling between all pairs of limb movements was
      found to increase with walking velocity, whereas no clear signs were observed
      that the switches from 2:1 to 1:1 frequency coordination and vice versa were
      preceded by loss of stability. Therefore, neither a purely biomechanical nor a
      purely dynamical model is optimally suited to explain these results. Instead, an
      integrative model involving elements of both approaches seems to be required.

PMID- 11303523
TI  - 1942.

PMID- 11303524
TI  - Re: Safety and efficacy of the rapid four-step technique for cricothyrotomy using
      a Bair Claw.

PMID- 11303525
TI  - Re: Safety and efficacy of the rapid four-step technique for cricothyrotomy using
      a Bair Claw.

PMID- 11303527
TI  - Clustering of 1p36 breakpoints distal to 1p36.2 in hematological malignancies.

PMID- 11303526
TI  - Pneumomediastinum in association with MDMA ingestion.

PMID- 11303528
TI  - A healthy old age: realistic or futile goal? Exercise programmes benefit even
      those who are most severely disabled.

PMID- 11303529
TI  - A healthy old age: realistic or futile goal? Training showed noticeable
      improvement in elderly women.

PMID- 11303531
TI  - Who should care for people with learning disabilities. Community learning
      disability nurses must get recognition they deserve.

PMID- 11303530
TI  - Who should care for people with learning disabilities? GPs need extra time to
      provide better services for these patients.

PMID- 11303532
TI  - Screening for central hypothyroidism is unjustified.

PMID- 11303533
TI  - Inequalities in health in Europe.

PMID- 11303534
TI  - Audit of oxygen prescribing. Treatment needs to be adjusted.

PMID- 11303535
TI  - Audit of oxygen prescribing. Oxygen prescribing has implications in neonatal
      care.

PMID- 11303536
TI  - Complications with reformulated one-alpha vitamin D.

PMID- 11303537
TI  - [Does the inhalation of a 1% L-menthol solution in the premedication of
      fiberoptic bronchoscopy affect coughing and the sensation of dyspnea?].
AB  - BACKGROUND: Inhalation of l-menthol inhibits cough and has been shown to reduce
      respiratory discomfort associated with loaded breathing. We investigated the
      effect of the inhalation of a 1% l-menthol solution in the premedication of
      fiberoptic bronchoscopy (FB) on the frequency of cough and the irritability of
      the tracheobronchial mucosa during FB in a blinded, randomized and placebo
      controlled study. METHODS: 64 pat. (30-78 yrs, 55 males) underwent routine FB.
      Premediction: atropine and hydrocodone s.c., inhalation of oxybuprocain by means
      of a jet nebulizer, sedation on demand. Verum-group: inhalation of 3 ml 1% l
      menthol-solution. Placebo-group: 3 ml 0.05% l-menthol (to provide the typical
      smell). Before and after inhalation peak respiratory flow (PEF) was registered,
      during FB the frequency of cough was measured. The bronchoscopist scored the
      irritability of the tracheobronchial mucosa using a visual analog scale. The
      patients answered a questionnaire addressing their perception of dyspnea and
      cough on the day after FB compared to the day before. RESULTS: The cough counts
      didn't show a significant difference between the groups. The irritability of the
      mucosa was increased in the verum group (main bronchus verum 62.2 +/- 22, placebo
      48.6 +/- 23 [mm vissual analog scale, p = 0.03]). Cough and dyspnea reported by
      the patients decreased on the day after FB significantly compared to the day
      before (no difference between the groups). The inhalation of 1% l-menthol induced
      a significant increase of the PEF (verum 307 +/- 103 pre, 329 +/- 84 post [l/min,
      p = 0.003]) compared to placebo. CONCLUSIONS: The inhalation of 1% l-menthol did
      not enhance the tolerability of the FB. However, l-menthol induced a significant
      increase of the PEF immediately after inhalation. Finally sensation of dyspnea
      was decreased in both groups at the day post FB.

PMID- 11303538
TI  - [Three new Nadejdolepis Spasskii & Sasskaya, 1954 (Cestoda: Hymenolepididae)
      parasites of Charadrii (Aves) from Tasmania].
AB  - Three species of Nadejdcolepis from Tasmania, Australia, are described and
      illustrated. N. burgessi n. sp., a parasite of Charadrius ruficapillus, is 4-6 mm
      long, with rostellar nitiduloid hooks 63-66 microm long, a short evaginated
      cirrus 13-16 microm long with a short collar of thin spines 1 microm long, a
      narrow and tubular sclerotinoid vagina 40-50 long and 3-4 microm in diameter with
      a little ampulla 3-5 microm in diameter at the proximal end, and a membranous
      atrial segment with smooth, short (1 microm) and compact spines which are
      sometimes difficult to observe. N. smithi n. sp., a parasite of 40-50 long and 3
      4 microm in diameter with a little ampulla 3-5 microm in diameter at the proximal
      end, and a membranous atrial segment with smooth, short (1 microm) and compact
      spines which are sometimes difficult to observe. N. smithi n. sp., a parasite of
      C. ruficapillus and Arenaria interpres, is 2-3.5 mm long, with rostellar
      nitiduloid hooks 90-98 microm long, a short evaginated cirrus (13 x 6.5 microm)
      with a short collar of thin 'bristles' of decreasing length (2-3 microm) and
      prolonged by a short and thin stylet, a sclerotinoid and conical vagina of 20 x 6
      microm, with an ovoid ampulla 6-7 x 4-9 at its slender end, and a membranous
      atrial segment like that of the preceding species. N. kinsellai n. sp., a
      parasite of C. ruficapillus is 25-40(?) mm long, with rostellar nitiduloid hooks
      89-93 microm long, a fusiform genital atrium 100 x 30 microm long with a very
      narrow pore, and a very long narrow cirrus-sac, which is cylindrical (not
      fusiform), has its aporal extremity lying in the preceding proglottis and has a
      slender uninterrupted wall without helicoid fibres. The poral extremity of the
      cirrus-sac is fastened by a long transverse muscle. An evaginated cirrus was not
      observed. The invaginated ejaculatory canal has two successive types of spines: a
      subterminal short portion (20-25 microm) with thick spines, followed by a long
      portion (100-120 microm) with numerous thin and compact 'bristles' 5 microm long.
      There is a very long convoluted spermatic duct (400-500 microm). The membranous
      tubular vagina is long (400-450 microm), thick-walled but not muscular and
      convoluted anterior to the distal part of the cirrus-sac; a chitinoid chamber,
      copulatory segment and sphincter are absent. Nadejdolepis species parasitic in
      Charadrii are reviewed. None of the species previously reported presents
      anatomical features similar to the three new species. N. kinsellai has
      morphological characters which differ in detail from other species in the genus.
      Hymenolepis (Hymenolepis) mudderbugtenensis Deblock & Rose, 1962 is transferred
      to the genus Nadejdolepis.

PMID- 11303539
TI  - Subscapular mass in a 68-year-old woman.

PMID- 11303540
TI  - Co-existence of the roles of the clinician, teacher and scientist within the same
      general practitioner. Mission impossible?

PMID- 11303541
TI  - Patients in primary health care diagnosed and treated as heart failure, with
      special reference to gender differences.
AB  - OBJECTIVE: The aim of the present study was to describe patients considered to
      have had heart failure (HF), or were being treated for HF, in a defined area in
      primary health care, e.g. diagnostic procedures, aetiologic diseases and
      management, and to evaluate whether there is a difference between the genders.
      DESIGN: Descriptive retrospective investigation. SETTING: Atvidaberg community
      situated in southeast Sweden, 12 400 inhabitants. PATIENTS: 256 patients treated
      for symptomatic HF. MAIN OUTCOME MEASURES: Prevalence, aetiology, diagnostic
      procedures and management of HF and differences between the genders. RESULTS: The
      diagnosis of HF was based on an objective evaluation of cardiac function in only
      31% of the patients. Ischaemic heart disease (IHD) was the predominant associated
      disease, followed by hypertension. Therapy included diuretics (84%), angiotensin
      converting enzyme (ACE) inhibitors (56%) and digoxin (40%). Only 52% had optimal
      doses of ACE inhibitors. Women had a significantly higher mean age and their
      diagnoses were based on an objective diagnostic test (echocardiography) in only
      20%. Women were prescribed ACE inhibitors to a lesser extent (43%) than men (64%)
      and with a lower optimal dose (44% versus 56% in men). CONCLUSION: There is still
      room for improvement in the management of HF in primary health care, especially
      in women, where the diagnosis is not generally based on an objective evaluation
      of cardiac function and where the treatment to a lesser extent than in men
      includes ACE inhibitors.

PMID- 11303542
TI  - A survey of subjects with present or previous atrial fibrillation in a Swedish
      community.
AB  - OBJECTIVE: A study of subjects with known atrial fibrillation (AF) in a Swedish
      community. DESIGN: A survey of subjects with present, or previous, AF (at 30
      September 1998) identified through medical records. SETTING: A community in the
      Stockholm Metropolitan area. RESULTS: Altogether 230 subjects, mean age 73 years,
      with a history of AF were identified (140 men and 90 women). One-hundred-and
      forty-nine patients were identified as having chronic, irreversible AF (65%). Of
      those with chronic AF, heart failure was noted in 53%, a valvular disease in 8%,
      hypertension in 32%, coronary heart disease in 36%, diabetes in 17% and an
      earlier ischaemic cerebrovascular episode in 30%. Hypertension was found as a
      significant factor for earlier ischaemic cerebrovascular episodes (OR 2.45, 95%
      CI 1.20-5.19). Anticoagulant treatment was prescribed in 32% out of those with
      chronic AF. The estimated overall occurrence of subjects with present, or a
      history of, AF was 0.7% in the community and 1.4% when standardising by age and
      sex to the whole Swedish population. CONCLUSION: AF is a common arrhythmia in
      Sweden, with an estimated occurrence of 1-1.5%, but despite a high rate of
      ischaemic cerebrovascular events in chronic AF (30%) a low prescription of
      anticoagulants.

PMID- 11303543
TI  - An assessment of structured care assistance in the management of patients with
      type 2 diabetes in general practice.
AB  - OBJECTIVE: To study differences in diabetes-related parameters in type 2 diabetic
      patients treated with the support of a Diabetes Service compared to conventional
      general practice care. DESIGN: Parallel clinical trial with randomisation at
      practice level. SETTING: Fifteen general practices. PATIENTS: Type 2 diabetic
      patients, aged < 76 years, treated by a GP. MAIN OUTCOME MEASURES: Level of
      glycated haemoglobin (HbA1c). RESULTS: 246 patients entered the study. Final mean
      HbA1c of all evaluable patients allocated to the intervention (n = 84) was 7.1+/
      1.2%, vs 7.5+/-1.8% in the controls (n = 140) (p = 0.06). Patients who were
      initially poorly controlled (Fasting Blood Glucose > 10 mmol/l) had a
      significantly lower final HbA1c if they were in an intervention practice
      (p=0.001). Fewer patients in intervention practices were referred to hospital
      specialists (1 vs 14). CONCLUSIONS: Support by the Dutch Diabetes Service did not
      significantly influence glycated haemoglobin. The subgroup of initially poorly
      controlled patients developed a significantly lower HbA1c in intervention
      practices (supported by a Diabetes Service) than in control practices.

PMID- 11303544
TI  - Walking for exercise - immediate effect on blood glucose levels in type 2
      diabetes.
AB  - OBJECTIVE: To determine the immediate effect of walking on blood glucose levels
      in patients with type 2 diabetes. DESIGN: Participating patients walked for half
      an hour on one occasion and on another day they remained physically inactive for
      half an hour. Blood glucose was measured before and after walking and resting.
      SETTING: Krokom in the north of Sweden. PATIENTS: Thirty-nine persons with type 2
      diabetes, aged 63 (SD 8.5). MAIN OUTCOME MEASURES: Difference of blood glucose
      levels before and after walking and resting respectively. RESULTS: Post-walk
      glycaemic levels were reduced by 2.2 mmol/l (SD 1.5). No significant reduction
      could be observed after a period of physical rest. CONCLUSION: Walking can be
      safely employed in groups or individually as an introduction to low-intensity
      exercise and as a demonstration of its blood glucose lowering effect in type 2
      diabetes.

PMID- 11303545
TI  - Poor performance in the mini-mental state examination due to causes other than
      dementia.
AB  - OBJECTIVE: The aim of this study was to examine the extent to which causes other
      than dementia contribute to poor performance on the Mini-Mental State Examination
      (MMSE). DESIGN: Cross-sectional population-based study. SETTING: Municipality of
      Lieto, Finland. SUBJECTS: The study population consisted of all individuals
      residing in Lieto and born in or before 1926. A total of 1196 individuals, 93% of
      those eligible, participated. MAIN OUTCOME MEASURES: The MMSE was implemented
      following interviews and clinical examinations. Whenever an individual was unable
      to complete any individual item on the MMSE, the nurse recorded causes and
      assessed whether poor performance was mainly caused by dementia or other reasons.
      RESULTS: Poor test performance due to causes other than dementia was recorded in
      122 (10.2%) individuals (4% of those in the 64-74 years group, 15% in the 75-84
      years group and 42% in the group of 85 years of age or older). The most common
      causes were poor vision and hearing, deficient schooling and consequences of
      stroke. CONCLUSION: Ten percent of the elderly population had symptoms
      contributing to poor performance on the MMSE. Physicians should therefore
      consider and record co-morbidity in the testing situation, especially in very old
      individuals.

PMID- 11303546
TI  - A retrospective study of functional ability among people with dementia when
      admitted to group-dwelling.
AB  - OBJECTIVE: To describe functional ability among people with dementia when
      admitted to group-dwelling (GD) during different time periods, and the
      probability of their remaining in these units for the rest of their lives.
      DESIGN: Retrospective study of functional ability and likelihood of staying in
      GD. SETTING: Thirteen GD units in the Sundsvall region, Sweden. SUBJECTS: One
      hundred-and-forty-two demented people admitted to GD in the period 1986-1996.
      MAIN OUTCOME MEASURES: Ability to manage personal care and somatic and
      psychiatric status were measured with the use of a rating scale. RESULT: On
      comparing people over the years, a significant increase was found in the need of
      assistance to manage everyday life on admission to GD. The likelihood of living
      the rest of life in GD has increased over time. CONCLUSIONS: Increasing
      dependency and increasing probability of remaining in GD may influence the
      intention of GD as a unique way of caring for people with dementia. It is crucial
      to consider these changes in order to encourage the development of GD.

PMID- 11303547
TI  - Acupressure treatment of morning sickness in pregnancy. A randomised, double
      blind, placebo-controlled study.
AB  - OBJECTIVE: To find out whether acupressure wristband can alleviate nausea and
      vomiting in early pregnancy. DESIGN: Double-blind, placebo-controlled study.
      SUBJECTS: 97 women with mean gestational length completed 8-12 weeks. MAIN
      OUTCOME MEASURES: Symptoms were recorded according to intensity, duration and
      nature of complaints. RESULTS: 71% of women in the intervention group reported
      both less intensive morning sickness and reduced duration of symptoms. The same
      tendency was seen in the placebo group, with 59% reporting less intensity and 63%
      shorter duration of symptoms. However, a significance level of 5% was reached
      only in the case of duration of symptoms, which was reduced by 2.74 hours in the
      intervention group compared to 0.85 hours in the placebo group (p = 0.018).
      CONCLUSIONS: Acupressure wristband might be an alternative therapy for morning
      sickness in early pregnancy, especially before pharmaceutical treatment is
      considered.

PMID- 11303548
TI  - Predictors for referral to physiotherapy from general practice.
AB  - OBJECTIVE: The aim of the study was to describe the referral rates from general
      practice to physiotherapists and to investigate possible predictors for referral.
      METHODS: Referral rates per 100 patients per year were obtained from the health
      insurance register of the county of Aarhus. General Practitioner (GP)
      characteristics were obtained via a questionnaire to all GPs in the county.
      RESULTS: A total of 38 231 referred patients from 260 practices were included.
      Twice as many women as men were referred. Referral rates varied from 1.6% to
      13.2% between practices. Of the explored predictors "practice location", "female
      GP practices" and "GPs reporting frequent contact with physiotherapist regarding
      the treatment of individual patients" were statistically significant, but
      explained little of the variance in referral rates. CONCLUSION: The examined
      practice and GP characteristics explain little of the substantial variation in
      referral rates. In view of increasing health care expenses and the need for
      quality assurance, the large variation in referral rates warrants reflection and
      further research on indications for and possible benefit from physiotherapy.

PMID- 11303549
TI  - Estimated prevalences of respiratory symptoms, asthma and chronic obstructive
      pulmonary disease related to detection rate in primary health care.
AB  - OBJECTIVE: To assess the prevalence of respiratory symptoms, asthma and chronic
      obstructive pulmonary disease (COPD), and to relate it to an estimated detection
      rate in primary health care. DESIGN: A two-staged study with a cross-sectional
      survey and a clinical validation. SETTING: The adult population of Varmland, a
      county in Sweden. SUBJECTS: 4814 persons completed the survey and 206 the
      confirmative validation study. MAIN OUTCOME MEASURES: Prevalence of respiratory
      symptoms, of asthma and COPD. RESULTS: More than 40% reported respiratory
      symptoms. Wheeze was reported by 8.0%, shortness of breath by 11.4% and sputum
      production by 14.1%. Smoking was more common among women than among men. The
      prevalence of asthma was 8.2% and COPD 2.1%. Of persons with asthma, 33% were
      estimated to be undiagnosed, 67% used medication and nearly 60% attended primary
      health care services. CONCLUSION: Respiratory symptoms as well as asthma were
      common in this study and equivalent to earlier findings. The difference between
      the epidemiologically estimated prevalence of asthma and the lower detection rate
      in primary health care can be explained by at least three factors: persons who
      did not seek any care, were underdiagnosed or attended other health care
      providers.

PMID- 11303550
TI  - Antibiotic prescription for acute sinusitis in otherwise healthy adults. Clinical
      cure in relation to costs.
AB  - OBJECTIVE: To determine which treatment strategy offers the most cost-effective
      option in managing acute sinusitis. DESIGN: The modelling procedure included five
      clinical strategies, varying from "wait and see for a week", to "prescribing
      antibiotics selectively" to "prescribing antibiotics immediately" and to
      "performing further diagnostics". SETTING: Outpatient clinics and primary health
      care. PATIENTS: Data were derived from clinical trials that included otherwise
      healthy patients with acute sinusitis. MAIN OUTCOME MEASURES: The marginal cost
      effectiveness. RESULTS: By using the strategy "wait and see for a week", 91.5% of
      the patients, by "prescribing antibiotics selectively", 93.2%, of the patients,
      and by "prescribing antibiotics immediately", 94.5% of the patients were cured
      after a 1-week period. The costs for curing one additional patient were Dutch
      Florin (DFL) 516 when antibiotics were selectively prescribed, and DFL 882 when
      antibiotics were immediately prescribed. Further diagnostic procedures did not
      improve outcome in terms of marginal cost-effectiveness. CONCLUSIONS: In patients
      presenting with acute sinusitis, postponing antibiotics for 1 week is the most
      cost-effective strategy.

PMID- 11303551
TI  - Report from University of Birmingham.

PMID- 11303552
TI  - The patient-centred interview: the key to biopsychosocial diagnosis and
      treatment.
AB  - The article reports on some ideas and experiences gained from a holistic approach
      to working with patients and introduces a viewpoint that includes opinions on how
      postmodernism, the biopsychosocial model and a patient-centred interviewing style
      can change traditional, biomedical-oriented medicine. During the past 10 years,
      we have been instructing medical students in the use of this patient-centred
      interviewing model and have trained experienced general practitioners (GPs) in
      adopting it in 2-year family-oriented continuing medical education courses. We
      believe that doctors and other health care providers, particularly in primary
      care settings, need a comprehensive concept of human health and illness, and that
      skill in patient-centred interviewing is the product of a deep learning process.
      In conclusion, we have learned that a successful patient-centred interview helps
      the GP to better understand the patient and helps to explain the data that the
      patient presents. Patient-centred orientation and interviewing also change the
      communication between doctor and patient in a direction which supports the
      patient's and his/her family members' own resources in the healing process.

PMID- 11303553
TI  - Biological effects of acetamide, formamide, and their mono and dimethyl
      derivatives: an update.

PMID- 11303554
TI  - Comparative QSAR: on the toxicology of the phenolic OH moiety.
AB  - In this report we consider the effect of substituents on phenol toxicity and show
      how the parameters used in Quantitative Structure-Activity Relationships (QSAR)
      can be used to draw mechanistic inferences of value in understanding the reasons
      behind the various types of toxicity. In particular, we are interested in gaining
      clearer insight into mechanisms via the Hammett-type parameters sigma, sigma(-),
      sigma(+) and octanol/water parti tion coefficients. Particular attention is given
      to the role of radical reactions and their role in attacking DNA to cause cancer
      or estrogenic toxicity.

PMID- 11303555
TI  - Preparation of oligodeoxynucleotides containing 5-(N-methylpiperazinyl) and 5
      benzyloxymethyl uracils.
AB  - Deprotected compounds 1 and 9 were allowed to react with 4,4'-dimethoxytrityl
      chloride in pyridine to give 5'-O-DMT nucleosides 2 and 10. The 3'
      phosphoramidites 4 and 11 were incorporated into oligodeoxynucleosides (ODNs).
      The hybridization properties of the modified ODNs with their complementary DNA
      strands were studied. Interesting results were obtained when 11 was inserted as a
      bulged nucleoside into TWAs, duplexes, and triplexes.

PMID- 11303556
TI  - Novel synthesis of seco type of acyclo C-nucleosides of 1,2,4-triazole and 1,2,4
      triazol.
AB  - The seco C-nucleosides 3-(1,2,3,4,5-penta-O-acetyl-D-gluco- and D-galacto
      pentitol-1-yl)-1H-1,2,4-triazoles (8 and 9) were obtained in a one pot by
      deamination and dethiolation of 4-amino-3-(D-gluco- and D-galacto-pentitol-1-yl)
      5-mercapto-1,2,4-triazoles (1 and 2), respectively, using sodium nitrite in
      orthophosphoric acid and subsequent acetylation. Condensation of 1, 2, and 4
      amino-3-(D-glycero-D-gulo-hexitol-1-yl)-5-mercapto-1,2,4-triazole (12) with
      phenacylbromide (11) afforded the corresponding 3-(D-gluco-, D-galactopentitol-1
      yl) and 3-(D-glycero-D-gulo-hexitol-1-yl)-6-phenyl-7H-1,2,4-triazolo[3,4
      b][1,3,4] thiadiazines (15, 16, and 17). Acetylation of 15-17 gave the penta- and
      hexa-O-acetyl derivatives 18-20, respectively. The structures were confirmed by
      using 1H, 13C, and 2D NMR spectra, DQFCOSY, HMQC, and HMBC experiments. The
      favored conformational structures were deduced from the vicinal coupling
      constants of the protons.

PMID- 11303557
TI  - Synthesis of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-substituted-benzene
      thymidine mimics, some related alpha-anomers, and their evaluation as antiviral
      and anticancer agents.
AB  - A group of unnatural 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluorobenzenes having
      a variety of C-5 substituents (H, Me, F, Cl, Br, I, CF3, CN, NO2, NH2), designed
      as thymidine mimics, were synthesized for evaluation as anticancer and antiviral
      agents. The coupling reaction of 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-alpha-D
      ribofuranosyl chloride with an organocadmium reagent [(2,4-difluorophenyl)2Cd]
      afforded a mixture of the alpha- and beta-anomeric products (alpha:beta = 3:1 to
      10:1 ratio). Treatment of the alpha-anomer with BF3.Et2O in nitroethane at 110
      120 degrees C for 30 min was developed as an efficient method for epimerization
      of the major alpha-anomer to the desired beta-anomer. The 5-substituted (H, Me,
      Cl, I, NH2) beta-anomers exhibited negligible cytotoxicity in a MTT assay (CC50 =
      10(-3)-10(-4) M range), relative to thymidine (CC50 = 10(-3)-10(-5) M range),
      against a variety of cancer cell lines. In contrast, the 5-NO2 derivative was
      more cytotoxic (CC50 = 10(-5)-10(-6) M range). A number of 5-substituted beta
      anomers, and some related alpha-anomers, that were evaluated using a wide variety
      of antiviral assay systems [HSV-1, HSV-2, varicella-zoster virus (VZV), vaccinia
      virus, vesicular stomatitis, cytomegalovirus (CMV) and human immunodeficiency
      (HIV-1, HIV-2) viruses], showed that this class of unnatural C-aryl nucleoside
      mimics are inactive antiviral agents.

PMID- 11303558
TI  - Synthesis and characterization of polyamine-based biomimetic catalysts as
      artificial ribonuclease.
AB  - Several polyamine derivatives (I-V) conjugated with or without an intercalative
      moiety were prepared as ribonuclease mimics. Although no DNA-cleaving activity
      was observed for all compounds tested, mimics I, III, and V bearing an
      intercalative moiety along with the primary amine and/or imidazole moieties
      exhibited potent RNA-cleaving activity at near physiological pH. The RNA-cleaving
      reactions of the compounds show characteristic bell-shaped pH dependency, and the
      optimal pH values for III and V were well correlated to the pKa values of their
      active sites, primary amine, and imidazole moieties.

PMID- 11303559
TI  - Binding of a porphyrin conjugate of Hoechst 33258 to DNA. I. UV-visible and
      melting studies detect multiple binding modes to a 12-mer nonself-complementary
      duplex.
AB  - Relative to ligand-free duplex DNA, the melting temperature of the 1:1 complex of
      the duplex d(CGAATTGTATGC):d(GCATACAATTCG) with the conjugate of Hoechst 33258
      with a des-metalloporphyrin, increased from 42 to 60.5 degrees C indicating
      strong ligand binding. UV-vis spectrophotometric titration detected more than one
      class of binding site (apparent dissociation constants approximately 0.2 microM
      for simple noncooperative binding and 1 microM for the simultaneous cooperative
      mode with Hill coefficient approximately 2).

PMID- 11303560
TI  - Binding of a porphyrin conjugate of Hoechst 33258 to DNA. II. NMR spectroscopic
      studies detect multiple binding modes to a 12-mer nonself-complementary duplex
      DNA.
AB  - We have probed by 1H NMR spectroscopy the molecular basis of the interaction
      between Hoechst 33258 conjugated to a des-metalloporphyrin and a non self
      complementary duplex DNA sequence, designed on the known chemical nuclease
      selectivity of this system. The imino NMR spectra are consistent with two
      distinct families of structure, that is, PORHOE binding either way along the
      duplex. 2D spectral, T2, and linewidth data suggest multiple species within the
      two conformational families.

PMID- 11303561
TI  - Binding of a desmetallo-porphyrin conjugate of Hoechst 33258 to DNA. III. Strong
      bonding to single-strand oligonucleotides.
AB  - The binding of the conjugate of Hoechst 33258 with 5,10,15,20-tetrakis (1-methyl
      4-pyridyl)-21H,23H-porphyrin (PORHOE) to single-strand DNA has been detected by
      UV-vis spectrophotometry and 1H-NMR. The red-shift of porphyrin Soret band with
      strong hypochromicity indicates that the porphyrin moiety dominates in the
      interaction of the PORHOE with ssDNA. The affinity constants of PORHOE for
      d(GCATACAATTCG) or d(CGAATTGTATGC) were determined to be >10(5) M(-1), with
      strong cooperativity.

PMID- 11303562
TI  - Synthesis of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-substituted
      benzenes: "thymine replacement" analogs of thymidine for evaluation as anticancer
      and antiviral agents.
AB  - A group of unnatural 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluorobenzenes having
      a variety of C-5 two-carbon substituents [-C...C-X, X = I, Br; -C...CH; (E)-CH=CH
      X, X = I, Br; -CH=CH2; -CH2CH3; -CH(N3) CH2Br], designed as nucleoside mimics,
      were synthesized for evaluation as anticancer and antiviral agents. The 5
      substituted (E)-CH=CH-I and -CH2CH3 compounds exhibited negligible cytotoxicity
      in a MTT assay (CC50 = 10(-3) to 10(-4)M range), relative to thymidine (CC50 =
      10(-3) to 10(-5)M range), against a variety of cancer cell lines. In contrast,
      the C-5 substituted -C...C-I and -CH(N3)CH2Br compounds were more cytotoxic (CC50
      = 10(-5) to 10(-6)M range). The -C...C-I and -CH2CH3 compounds exhibited similar
      cytotoxicity against non-transfected (KBALB, 143B) and HSV-1 TK+ gene transfected
      (KBALB-STK, 143B-LTK) cancer cell lines expressing the herpes simplex virus type
      1 (HSV-1) thymidine kinase gene (TK+). This observation indicates that expression
      of the viral TK enzyme did not provide a gene therapeutic effect. The parent
      group of 5-substituted compounds, that were evaluated using a wide variety of
      antiviral assay systems [HSV-1, HSV-2, varicella-zoster virus (VZV), vaccinia
      virus, vesicular stomatitis, cytomegalovirus (CMV), and human immunodeficiency
      (HIV-1, HIV-2) viruses], showed that this class of unnatural C-aryl nucleoside
      mimics are inactive and/or weakly active antiviral agents.

PMID- 11303563
TI  - Efficient methods for the synthesis of [2-15N]guanosine and 2'-deoxy[2
      15N]guanosine derivatives.
AB  - The nucleophilic addition-elimination reaction of 2',3',5'-tri-O-acetyl-2-fluoro
      O6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of
      triethylamine afforded the N2-benzyl[2-15N]guanosine derivative (13) in a high
      yield, which was further converted into the N2-benzoyl[2-15N] guanosine
      derivative by treatment with ruthenium trichloride and tetrabutylammonium
      periodate. A similar sequence of reactions of 2',3',5'-tri-O-acetyl-2-fluoro-06
      [2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(beta-D
      ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from
      guanosine, with potassium [15N]phthalimide afforded the N2-phthaloyl [2
      15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-beta-D
      ribofuranosyl)-6-chloro-2-[15N]phthalimido-9H-purine (17; 64%), respectively.
      Compounds 15 and 17 were then efficiently converted into 2',3',5'-tri-O-acetyl [2
      15N]guanosine. The corresponding 2'-deoxy derivatives (16 and 18) were also
      synthesized through similar procedures.

PMID- 11303564
TI  - The chemical stability of S-(2-acylthioethyl) and S-acyloxymethyl protected
      thymidylyl-3',5'-thymidine phosphoromonothiolates and their deacylation products
      in aqueous solution.
AB  - The hydrolytic stability of the S-(2-acetylthioethyl) (1a,b), S-(2
      pivaloylthioethyl) (2a,b), and S-acetyloxymethyl (3a,b) protected Rp and Sp
      phosphoromonothiolates of 3',5'-TpT has been studied. Rather unexpectedly, an
      intramolecular hydroxide ion catalyzed acetyl migration from the protecting group
      to the nucleoside 3'- and 5'-hydroxy functions was found to compete with the
      intermolecular displacement of the AcSCH2CH2S- or AcOCH2S-ligand from the
      phosphorus atom of 1a,b and 3a,b, respectively. With the S-pivaloylthioethyl
      derivative 2a,b no such reaction took place. Additionally, the kinetics of the
      cleavage of the S-(2-mercaptoethyl) group from 4a,b, the products of enzymatic
      deacylation of 1a,b and 2a,b, were studied as a function of pH.

PMID- 11303565
TI  - New 3'-deoxythymidines bearing a nucleophilic 3'-substituent.
AB  - New potential cancer-driven as well as HIV-driven nucleoside heteroanalogs, such
      as 3'-thio- and 3'- as well as 5'-selenosubstituted thymidines, have been
      synthesized. We also report an effective method for the preparation of novel
      nucleoside derivatives, bis(deoxynucleoside) diselenides, in nearly quantitative
      yields. The North conformation is significantly populated in the conformational
      equilibrium for 3'-alpha-alkylthiothymidines.

PMID- 11303566
TI  - Influencing micropropagation and somatic embryogenesis in mature trees by
      manipulation of phase change, stress and culture environment.
AB  - This review focuses on clonal propagation of mature trees by tissue culture. Most
      trees have marked phase changes that result in a decline in their potential for
      somatic embryogenesis or micropropagation. By altering conditions of the source
      material ex vitro, or by changing in vitro conditions encountered by the explant,
      rejuvenation and increased propagation can sometimes be accomplished. Various
      methods of enhancing micropropagation are reviewed, with particular emphasis on
      manipulations that involve application of osmotic, temperature or hormonal
      stress.

PMID- 11303567
TI  - Quercus species differ in water and nutrient characteristics in a resource
      limited fall-line sandhill habitat.
AB  - We compared co-occurring mature Quercus laevis Walt. (turkey oak), Q. margaretta
      Ashe (sand post oak) and Q. incana Bartr. (bluejack oak) trees growing in
      resource-limited sandhill habitats of the southeastern United States for water
      and nutrient characteristics. The Quercus spp. differed in their distribution
      along soil water and nutrient gradients, and in their access to and use of water,
      even though the study year was wetter than average with no mid-season drought.
      Quercus laevis had the greatest access to soil water (least negative pre-dawn
      water potential, psi(pd)) and the most conservative water-use strategy based on
      its relatively low stomatal conductance (g(s)), high instantaneous water-use
      efficiency (WUE), least negative midday water potential (psy(md)) and high leaf
      specific hydraulic conductance (K(L)). Quercus margaretta had the least
      conservative water-use characteristics, exhibiting relatively high g(s), low
      instantaneous WUE, most negative psi(md), and low K(L). Quercus margaretta also
      had a low photosynthetic nitrogen-use efficiency (PNUE), but a high leaf
      phosphorus concentration. Quercus incana had the poorest access to soil water,
      but intermediate water-use characteristics and leaf nutrient characteristics more
      similar to those of Q. laevis. There were no species differences for
      photosynthesis (A), leaf nitrogen on an area basis, or seasonally integrated WUE
      (delta13C). Both A and g(s) were positively correlated for each species, but A
      and g(s) were generally not correlated with psi(pd), psi(md) or delta psi(pd-md).
      Although we found differences in resource use and resource status among these
      sandhill Quercus spp., the results are consistent with the interpretation that
      they are generally drought avoiders. Quercus laevis may have an advantage on
      xeric ridges because of its greater ability to access soil water and use it more
      conservatively compared with the other Quercus spp.

PMID- 11303568
TI  - Photosynthetic nutrient-use efficiency in three fast-growing tropical trees with
      differing leaf longevities.
AB  - Differences in nutrient-use efficiency have been attributed to differences in
      leaf habit. It has been suggested that evergreens, with their longer-lived
      leaves, and therefore longer nutrient retention, are more efficient than
      deciduous species in their use of nutrients. In tropical trees, however, leaf
      life span is not always a function of whole-tree deciduousness, leading to the
      proposal that nutrient-use efficiency is better related to leaf life span than to
      leaf habit. It was predicted that potential photosynthetic nutrient-use
      efficiency (maximum potential photosynthesis/leaf nutrient content) would
      decrease with increasing leaf life span, whereas cumulative photosynthetic
      nutrient-use efficiency (carbon assimilated over a leaf's life span/total
      nutrients invested in a leaf) would increase with increasing leaf life span.
      Potential and cumulative photosynthetic nutrient-use efficiencies (with respect
      to nitrogen and phosphorus) were measured for three fast-growing tropical trees:
      Cedrela odorata L. (Meliaceae), Cordia alliodora (R. & P.) Cham. (Boraginaceae),
      and Hyeronima alchorneoides Allemao (Euphorbiaceae). Mean leaf life spans of the
      three species varied about threefold and ranged from 50 to 176 days. The
      predictions were partially supported: Cedrela odorata had the shortest-lived
      leaves and the highest potential nitrogen-use efficiency, whereas Hyeronima
      alchorneoides had the longest-lived leaves and the highest cumulative nitrogen-
      and phosphorus-use efficiencies. Potential phosphorus-use efficiency, however,
      was invariant among species. It is suggested that there are potential tradeoffs
      between leaf characteristics that lead to high potential and cumulative nutrient
      use efficiencies. High potential nutrient-use efficiency may be beneficial in
      high-nutrient environments, whereas high cumulative nutrient-use efficiency may
      be of greater benefit to species in low-nutrient environments.

PMID- 11303569
TI  - Acclimation of leaf characteristics of Fagus species to previous-year and current
      year solar irradiances.
AB  - To examine the effects of different solar irradiances on leaf characteristics at
      the leaf primordium and expansion stages, we shaded parts of branches in the
      upper canopies of two adult beech trees, Fagus crenata Blume and Fagus japonica
      Maxim., for 4 years. The treatments during the leaf primordium and leaf expansion
      stages, respectively, were: (1) high light and high light (H, control), (2) high
      light and low light (HL), (3) low light and low light (LL), and (4) low light and
      high light (LH). Both number of cell layers in palisade tissue and individual
      leaf area were affected by the previous-year irradiance, whereas cell length of
      palisade tissue was larger in LH leaves than in LL leaves, suggesting
      determination by current-year irradiance. Lamina chlorophyll/nitrogen ratio was
      higher in HL and LL leaves than in LH leaves, suggesting determination by current
      year irradiance. Diurnal minimum values of leaf water potential measured under
      sunlit conditions were lower in H and LH leaves than in HL and LL leaves.
      Effective osmotic adjustment was found in H and LH leaves, suggesting that leaf
      water relations were affected by current-year irradiance. Net photosynthetic rate
      and stomatal conductance measured under sunlight conditions were higher in H and
      LH leaves than in HL and LL leaves. Thus, effects of current-year irradiance had
      a greater effect on leaf-area-based daily carbon gain than previous-year
      irradiance.

PMID- 11303570
TI  - Tolerance of salinized floodplain conditions in a naturally occurring Eucalyptus
      hybrid related to lowered plant water potential.
AB  - Rising saline groundwater and reduced flooding frequency are causing dieback of
      Eucalyptus largiflorens F. Muell. along the Murray River in Australia. A green
      leaved variant of E. largiflorens, which is probably a hybrid with a local mallee
      species (E. gracilis F. Muell.), tolerates saline conditions better than the more
      common grey-leaved variant. The green variant exhibited more negative water
      potentials than the grey variant, and comparison with soil water potential
      profiles indicated that the green variant extracted water from slightly higher up
      the soil profile where the salt content was lower but the soil was drier.
      However, the stable isotopes of water (2H and 18O) in the xylem did not differ
      significantly between paired green and grey trees, suggesting that both variants
      used the same water source. The green variant may be able to extract water for a
      longer period from a given point in the soil profile and tolerate a higher salt
      concentration around its roots than the grey variant. Predawn leaf water
      potentials of both variants decreased with increasing salinity of groundwater and
      decreasing depth to the groundwater, probably because the roots were being
      progressively confined to soil with lower matric potential as groundwater
      discharge through transpiration progressively salinized soil up the profile. The
      green variant had a lower assimilation rate and stomatal conductance than the
      grey variant, although the differences were not statistically significant during
      most of the year. Discrimination of 13C indicated that the green variant had a
      higher leaf internal CO2 concentration than the grey variant, indicative of a
      greater biochemical limitation on photosynthesis, perhaps resulting from the
      effects of operating at lower water potentials. The green variant had
      significantly lower stem hydraulic conductivity than the grey variant, probably
      because of its smaller xylem vessel diameter and higher degree of embolism. The
      more conservative water use of the green variant and its ability to operate at
      lower water potential than the grey variant appear to underlie its ability to
      tolerate conditions of reduced useable water above the saline groundwater. This
      advantage appears to outweigh the costs of increased xylem embolism and reduced
      assimilation.

PMID- 11303571
TI  - Tapered conduits can buffer hydraulic conductance from path-length effects.
AB  - The model of West, Brown and Enquist showed that total hydraulic resistance in
      trees can be independent of path length, provided that vascular conduits taper
      sufficiently. This model assumes that the tree branch network is volume-filling,
      so that segment lengths increase exponentially from tree top to base. We show
      that partial buffering of hydraulic resistance from path-length effects can occur
      even for moderate tapering, and that this effect is stronger when segment lengths
      are fixed. Still needed are measurements of tracheary size and hydraulic
      resistance designed to test this model, which shows how hydraulic limitation of
      tree height growth may be mitigated.

PMID- 11303572
TI  - Characterization of the photosynthetic induction response in a Populus species
      with stomata barely responding to light changes.
AB  - The photosynthetic induction response is constrained by stomatal and biochemical
      limitations. However, leaves in some plants like Populus koreana x trichocarpa
      cv. Peace (a hybrid clone) may have little stomatal limitation because their
      stomata barely respond to changes in photon flux density (PFD). We examined the
      induction responses of leaves of well-watered and dehydrated P. koreana x
      trichocarpa plants grown in a high-light or a low-light regime. With an increase
      in PFD from 50 to 500 micromol m(-2) s(-1), steady-state stomatal conductance
      (g(s)) increased by only 0.25-8.2%, regardless of the initial g(s), but steady
      state assimilation rate (A) increased by 550-1810%. Photosynthetic induction
      times required to reach 50% (IT50) and 90% (IT90) of A at high PFD were 60-90 s
      and 210-360 s, respectively. Examination of the dynamic relationships between A
      and g(s), and between A and intercellular CO2 concentration, indicated that the
      induction limitation was imposed completely by the biochemical components within
      30-40 s after the PFD increase. Values of IT50 and IT90 were significantly higher
      in low-light leaves than in high-light leaves, whereas the induction state at 60
      s and the induction efficiency at 60 and 120 s after the increase in PFD were
      lower in low-light leaves than in high-light leaves. Dehydration reduced leaf
      water potential (psi) significantly, resulting in a significantly decreased
      initial g(s). Leaf water potential had no significant effects on induction time
      in high-light leaves, but a low psi significantly reduced the induction time in
      low-light leaves. We conclude that the photosynthetic induction response was
      limited almost completely by biochemical components because the stomata barely
      responded to light changes. The biochemical limitation appeared to be higher in
      low-light leaves than in high-light leaves. Mild water stress may have reduced
      steady-state A and g(s), but it had little effect on the photosynthetic induction
      response in high-light leaves.

PMID- 11303573
TI  - Interaction of nutrient limitation and elevated CO2 concentration on carbon
      assimilation of a tropical tree seedling (Cedrela odorata).
AB  - Carbon assimilation by Cedrela odorata L. (Meliaceae) seedlings was investigated
      in ambient and elevated CO2 concentrations ([CO2]) for 119 days, using small
      fumigation chambers. A solution containing macro- and micronutrients was supplied
      at two rates. The 5% rate (high rate) was designed to avoid nutrient limitation
      and allow a maximum rate of growth. The 1% rate (low rate) allowed examination of
      the effect of the nutrient limitation-elevated CO2 interaction on carbon
      assimilation. Root growth was stimulated by 23% in elevated [CO2] at a high rate
      of nutrient supply, but this did not lead to a change in the root:shoot ratio.
      Total biomass did not change at either rate of nutrient supply, despite an
      increase in relative growth rate at the low nutrient supply rate. Net
      assimilation rates and relative growth rates were stimulated by the high rate of
      nutrient addition, irrespective of [CO2]. We used a biochemical model of
      photosynthesis to investigate assimilation at the leaf level. Maximum rate of
      electron transport (Jmax) and maximum velocity of carboxylation (Vcmax) did not
      differ significantly with CO2 treatment, but showed a substantial reduction at
      the low rate of nutrient supply. Across both CO2 treatments, mean Jmax for
      seedlings grown at a high rate of nutrient supply was 75 micromol m(-2) s(-1) and
      mean Vcmax was 27 micromol m(-2) s(-1). The corresponding mean values for
      seedlings grown at a low rate of nutrient supply were 36 micromol m(-2) s(-1) and
      15 micromol m(-2) s(-1), respectively. Concentrations of leaf nitrogen, on a mass
      basis, were significantly decreased by the low nutrient supply rate, in
      proportion to the observed decrease in photosynthetic parameters. Chlorophyll and
      carbohydrate concentrations of leaves were unaffected by growth [CO2]. Because
      there was no net increase in growth in response to elevated [CO2], despite
      increased assimilation of carbon at the leaf level, we hypothesize that the rate
      of respiration of non-photosynthetic organs was increased.

PMID- 11303574
TI  - Shoot growth responses to light microenvironment and correlative inhibition in
      tree seedlings under a forest canopy.
AB  - To examine the mechanisms underlying crown development, I investigated the
      dependence of shoot behavior on light microenvironment in saplings of the
      evergreen broad-leaved tree species, Litsea acuminata (Bl.) Kurata, growing on a
      forest floor. The local light environment of individual shoots (shoot irradiance)
      and plants (plant irradiance, defined as the shoot irradiance of the most sunlit
      shoot of a plant) were analyzed as factors affecting shoot behavior. Daughter
      shoots that developed under partially sunlit conditions were longer and less
      leafy than daughter shoots developed under shaded conditions. Shoot production
      increased with increasing shoot irradiance. Terminal shoots receiving 5% or less
      of full sunlight produced 0.67 daughter shoots on average, whereas shoots
      receiving 10% or more of full sunlight produced 1.72 daughter shoots. In terminal
      shoots receiving 5% or less of full sunlight, the probability of producing no
      daughter shoots was about 63% when other shoots on the plant received 10% or more
      of full sunlight, but was < 35% where the rest of the plant was also shaded.
      Shoot death was observed only in shoots receiving 5% or less of full sunlight.
      The mortality of shaded shoots was higher in plants growing in high irradiance
      than in plants growing in low irradiance. The ecological significance of
      correlative inhibition (the enhanced mortality and reduced production of new
      shaded shoots in the presence of partially-sunlit shoots) is discussed.

PMID- 11303575
TI  - Carbon stocks and soil respiration rates during deforestation, grassland use and
      subsequent Norway spruce afforestation in the Southern Alps, Italy.
AB  - Changes in carbon stocks during deforestation, reforestation and afforestation
      play an important role in the global carbon cycle. Cultivation of forest lands
      leads to substantial losses in both biomass and soil carbon, whereas forest
      regrowth is considered to be a significant carbon sink. We examined below- and
      aboveground carbon stocks along a chronosequence of Norway spruce (Picea abies
      (L.) Karst.) stands (0-62 years old) regenerating on abandoned meadows in the
      Southern Alps. A 130-year-old mixed coniferous Norway spruce-white fir (Abies
      alba Mill.) forest, managed by selection cutting, was used as an undisturbed
      control. Deforestation about 260 years ago led to carbon losses of 53 Mg C ha(-1)
      from the organic layer and 12 Mg C ha(-1) from the upper mineral horizons (Ah,
      E). During the next 200 years of grassland use, the new Ah horizon sequestered 29
      Mg C ha(-1). After the abandonment of these meadows, carbon stocks in tree stems
      increased exponentially during natural forest succession, levelling off at about
      190 Mg C ha(-1) in the 62-year-old Norway spruce and the 130-year-old Norway
      spruce-white fir stands. In contrast, carbon stocks in the organic soil layer
      increased linearly with stand age. During the first 62 years, carbon accumulated
      at a rate of 0.36 Mg C ha(-1) year(-1) in the organic soil layer. No clear trend
      with stand age was observed for the carbon stocks in the Ah horizon. Soil
      respiration rates were similar for all forest stands independently of organic
      layer thickness or carbon stocks, but the highest rates were observed in the
      cultivated meadow. Thus, increasing litter inputs by forest vegetation compared
      with the meadow, and constantly low decomposition rates of coniferous litter were
      probably responsible for continuous soil carbon sequestration during forest
      succession. Carbon accumulation in woody biomass seemed to slow down after 60 to
      80 years, but continued in the organic soil layer. We conclude that, under
      present climatic conditions, forest soils act as more persistent carbon sinks
      than vegetation that will be harvested, releasing the carbon sequestered during
      tree growth.

PMID- 11303576
TI  - Xylem conductivity and vulnerability to cavitation of ponderosa pine growing in
      contrasting climates.
AB  - We examined the effects of increased transpiration demand on xylem hydraulic
      conductivity and vulnerability to cavitation of mature ponderosa pine (Pinus
      ponderosa Laws.) by comparing trees growing in contrasting climates. Previous
      studies determined that trees growing in warm and dry sites (desert) had half the
      leaf/sapwood area ratio (A(L)/A(S)) and more than twice the transpiration rate of
      trees growing in cool and moist sites (montane). We predicted that high
      transpiration rates would be associated with increased specific hydraulic
      conductivity (K(S)) and increased resistance to xylem cavitation. Desert trees
      had 19% higher K(S) than montane trees, primarily because of larger tracheid
      lumen diameters. Predawn water potential and water potential differences between
      the soil and the shoot were similar for desert and montane trees, suggesting that
      differences in tracheid anatomy, and therefore K(S), were caused primarily by
      temperature and evaporative demand, rather than soil drought. Vulnerability to
      xylem cavitation did not differ between desert and montane populations. A 50%
      loss in hydraulic conductivity occurred at water potentials between -2.61 and 
      2.65 MPa, and vulnerability to xylem cavitation did not vary with stem size.
      Minimum xylem tensions of desert and montane trees did not drop below -2.05 MPa.
      Foliage turgor loss point did not differ between climate groups and corresponded
      to mean minimum xylem tensions in the field. In addition to low A(L)/A(S), high
      K(S) in desert trees may provide a way to increase tree hydraulic conductivity in
      response to high evaporative demand and prevent xylem tensions from reaching
      values that cause catastrophic cavitation. In ponderosa pine, the flexible
      responses of A(L)/A(S) and K(S) to climate may preclude the existence of
      significant intraspecific variation in the vulnerability of xylem to cavitation.

PMID- 11303577
TI  - Clonal variation in morphology, growth, physiology, anatomy and ultrastructure of
      container-grown white spruce somatic plants.
AB  - We assessed clonal variation in morphological variables, mineral nutrition, root
      growth capacity, net photosynthesis, tannin distribution, and cuticle and
      epicuticular wax features within four families of white spruce (Picea glauca
      (Moench) Voss). Seeds were collected from four families obtained through
      controlled crosses among selected genotypes. For each family, plants were
      produced either from seeds (zygotic) or by somatic embryogenesis (clones). Each
      family was therefore represented by its zygotic seedlings and three clones.
      Within a family and under similar growth conditions, several clones differed
      significantly from the zygotic seedlings in height, root-collar diameter, needle
      dry mass, branch density, shoot dry mass, root dry mass, and length of needles.
      Branch density (number of first-order branches per cm height) of zygotic
      seedlings and clones varied from 0.8 to 1.4 branches cm(-1) and from 0.6 to 1.3
      branches cm(-1), respectively. Mean needle length of zygotic seedlings and clones
      ranged from 11 to 14 mm and from 11 to 17 mm, respectively. For many variables
      (height, dry mass of new roots, needle dry mass and branch density), differences
      among clones were significantly greater than differences among zygotic seedlings
      within a family. Tannins were more abundant in needles of clones than in needles
      of zygotic seedlings. In some clones, tannins occurred as a ribbon along the
      central vacuole, whereas in others they appeared as aggregates dispersed in the
      vacuole. Within a family, N, P and K showed considerable variations in their use
      efficiency. Interclonal variations were observed in root growth potential and net
      photosynthesis. Variations in growth and physiology reflect genetically
      determined differences among clones within a family.

PMID- 11303578
TI  - Carbon assimilation and nitrogen in needles of fertilized and unfertilized field
      grown Scots pine at natural and elevated concentrations of CO2.
AB  - Effects of elevated CO2 concentration ([CO2]) on carbon assimilation and needle
      biochemistry of fertilized and unfertilized 25-30-year-old Scots pine (Pinus
      sylvestris L.) trees were studied in a branch bag experiment set up in a
      naturally regenerated stand. In each tree, one branch was enclosed in a bag
      supplied with ambient [CO2] (360 micromol mol(-1)), a second branch was enclosed
      in a bag supplied with elevated [CO2] (680 micromol(-1)) and a control branch was
      left unbagged. The CO2 treatments were applied from April 15 to September 15,
      starting in 1993 for unfertilized trees and in 1994 for fertilized trees, which
      were treated with N in June 1994. Net photosynthesis, amount and activity of
      Rubisco, N, starch, C:N ratio and SLA of needles were measured during the growing
      season of 1995. Light-saturated net photosynthetic rates of 1-year-old and
      current-year shoots measured at ambient [CO2] were not affected by growth [CO2]
      or N fertilization. Elevated [CO2] reduced the amount and activity of Rubisco,
      and the relative proportion of Rubisco to soluble proteins and N in needles of
      unfertilized trees. Elevated [CO2] also reduced the chlorophyll concentration
      (fresh weight basis) of needles of unfertilized trees. Soluble protein
      concentration of needles was not affected by growth [CO2]. Elevated [CO2]
      decreased the Rubisco:chlorophyll ratio in unfertilized and fertilized trees.
      Starch concentration was significantly increased at elevated [CO2] only in 1-year
      old needles of fertilized trees. Elevated [CO2] reduced needle N concentration on
      a dry weight or structural basis (dry weight minus starch) in unfertilized trees,
      resulting in an increase in needle C:N ratio. Fertilization had no effect on
      soluble protein, chlorophyll, Rubisco or N concentration of needles. The decrease
      in the relative proportions of Rubisco and N concentration in needles of
      unfertilized trees at elevated [CO2] indicates reallocation of N resources away
      from Rubisco to nonphotosynthetic processes in other plant parts. Acclimation
      occurred in a single branch exposed to high [CO2], despite the large sink of the
      tree. The responses of 1-year-old and current-year needles to elevation of growth
      [CO2] were similar.

PMID- 11303579
TI  - Influence of weather on cork-ring width.
AB  - Ring-width series of cork from Quercus suber L. trees growing at two sites in
      Extremadura (southwestern Spain) were analyzed in relation to monthly
      precipitation and temperature, and to climatic indices combining both variables.
      Ring width of cork showed strong positive correlations with precipitation,
      especially during the fall and winter. Moderately low temperatures were favorable
      for cork growth, except in winter and during the onset of phellogen activity. We
      conclude that drought or temperature, or both, can limit cork growth during the
      annual drought period.

PMID- 11303580
TI  - Regeneration of phenotypically normal English elm (Ulmus procera) plantlets
      following transformation with an Agrobacterium tumefaciens binary vector.
AB  - A transformation system was developed for English elm (Ulmus procera Salisbury)
      using Agrobacterium tumefaciens C58 pMP90 p35SGUS/INTRON, allowing for the
      transfer of foreign genes and regeneration of phenotypically normal elm
      plantlets. The PCR analysis indicated that both nptII and uidA genes were stably
      inserted in the plant genome. beta-Glucuronidase histochemical and fluorimetric
      assays revealed expression of the uidA gene in the shoots, leaves, stems and
      roots of regenerated transgenic plants. The DNA-DNA hybridizations confirmed the
      presence of the uidA gene in regenerant plants. Factors influencing successful
      transformation and regeneration of elms included: identifying gene-transfer
      proficient Agrobacterium strains for use with elms; developing an infection
      protocol allowing T-DNA transfer while retaining the ability to remove inciting
      bacteria; and identifying selection conditions to eliminate non-transformed
      material and choice of regeneration medium to allow shoot production. The
      potential utility of an effective elm transformation and regeneration system in
      the control of Dutch elm disease is discussed.

PMID- 11303581
TI  - Measurement of sap flow in roots of woody plants: a commentary.
AB  - Measurements of sap flow in roots have recently been used to study patterns of
      resource acquisition by woody plants; however, the various thermometric methods
      employed have yielded disparate findings. These findings may be harmonized by
      accounting for the phenomenon of reverse sap flow in roots. We suggest that only
      methods capable of measuring slow and reverse rates of flow and that do not
      require assumptions of zero flow during the night are applicable to studies with
      roots. The heat ratio method and the constant power heat balance method fit these
      criteria, whereas the constant temperature heat balance, compensation heat pulse
      and thermal dissipation methods do not.

PMID- 11303582
TI  - A mycobacterium isolated from tissue cultures of mature Pinus sylvestris
      interferes with growth of Scots pine seedlings.
AB  - We isolated a rapidly growing, pigment-producing mycobacterium from senescent
      tissue cultures derived from mature Scots pine (Pinus sylvestris L.). The
      bacterium was found in three senescent suspension cultures and in a senescent
      protoplast culture. Growth of Scots pine cells had ceased in all of these
      cultures. Exogenous contamination was eliminated by rigorous surface
      sterilization of the buds with hypochlorite before aseptic removal of the bud
      scales. Based on biochemical and physiological properties and DNA sequence
      comparisons, the isolated mycobacterium did not belong to any known species. Its
      sequence most closely resembled those of Mycobacterium obuense (97%) and M.
      aichiense (96%). Tissue browning was frequently observed in callus or suspension
      culture of Scots pine. Because the effect of the mycobacterium on growth of
      undifferentiated tissues that were browning was difficult to evaluate, we applied
      the bacterium to Scots pine seeds in aseptic conditions. Seedlings grown in the
      presence of the mycobacterium had shorter hypocotyls than control seedlings and
      seedlings cocultivated with a Pseudomonas strain known to be harmless to plants.
      However, hypocotyl growth of seedlings cocultivated with another mycobacterium,
      M. chlorophenolicum, was similar to that observed in the presence of the isolated
      mycobacterium. Phenylalanine ammonia-lyase activity of seedlings cocultivated
      with the mycobacterium isolate was significantly higher than that of control
      seedlings or seedlings cocultivated with M. chlorophenolicum or Pseudomotnas
      fluorescens. We believe that this is the first report of the isolation of
      mycobacteria from tissue cultures of a tree. Our finding that the mycobacterium
      may interfere with the growth of Scots pine in vitro warrants further study.

PMID- 11303583
TI  - Morphostats: a missing concept in cancer biology.
AB  - The role of specific morphogens is well established in the determination of body
      plans in development. A variety of morphogens have been identified; others are
      suspected. Pathways have been delineated. In complex tissues, the ability to
      maintain fidelity of microarchitectural structure is crucial. Microarchitecture
      is a consequence of relationships among cells, not a function of single cells.
      Epithelial layers, in particular, are able to maintain their microarchitecture
      with remarkable accuracy over many decades despite recurrent damage, regular cell
      turnover, and complexity of structure. Nonetheless, metaplasia and
      transdifferentiation (change in tissue structure without cell dysplasia) do
      occur, suggesting that there is the possibility of loss of control or change of
      control of the microarchitecture. A strong inference to be derived from the above
      is that there are control systems and molecules and that these are derived from
      cells that are outside, but plausibly adjacent to, the respective epithelia. It
      is postulated is that there are morphogen-like controller molecules with
      morphogen-like functions in adult epithelial tissues. These are responsible for
      the maintenance of normal tissue microarchitecture. Because the function of these
      putative molecules is maintenance of tissue structure, I have chosen to call them
      morphostats by analogy with morphogens. It seems plausible that morphostats and
      morphogens may constitute overlapping families of molecules. Evidence for the
      existence of morphostats can be derived from a variety of in vivo and in vitro
      data and from studies of normal tissue, precancer, and cancer, including: (a) the
      existence but rarity of metaplasia and transdifferentiation; (b) the fact that
      metaplasias are multicentric and are only one step from normal but do not show
      any consistent epithelial mutation; (c) the genesis of animal cancers by simple
      transplantation of tissues into the wrong environment and the evidence that
      epithelial mutation is not a feature of such transplantation carcinogenesis; (d)
      the fact that carcinogenesis occurs frequently at the junctions of different
      epithelial types, e.g., squamocolumnar junctions in gastrointestinal and genital
      tracts; (e) the fact that cancer-associated fibroblasts can stimulate
      proliferation in transformed cells but not influence normal cells; and (f) the
      failure to grow most epithelial organs in a fully differentiated structural
      pattern in monolayer culture. It is suggested that morphostats may function like
      morphogens inasmuch as they may act via a diffusion gradient from source
      mesenchymal cells and provide architectural instruction for complex adult
      epithelia. Morphostats may influence architecture via control of cell adhesion,
      apoptosis, and proliferation. Some specific predictions follow from this
      hypothesis, most notably, a new two-hit model of cancer: one mutation in an
      epithelial cell resulting in disruption of cell function and structure (e.g.,
      dysplasia); and the other in a mesenchymal or other supporting cell resulting in
      disruption of tissue microarchitecture. The corollary of this is that there will
      be mesenchymal mutations producing microarchitectural abnormalities without
      epithelial dysplasia and vice versa. Disruption of the functions of morphostats
      may result in a variety of abnormalities. Such disruption may be a key event in
      carcinogenesis.

PMID- 11303584
TI  - Human papillomavirus and long-term oral contraceptive use increase the risk of
      adenocarcinoma in situ of the cervix.
AB  - We examined United States Surveillance, Epidemiology, and End Results incidence
      data and conducted a population-based case-control study to examine the role of
      human papillomavirus (HPV) and oral contraceptive (OC) use in the etiology of
      adenocarcinoma in situ of the cervix (ACIS). One hundred and fifty women
      diagnosed with ACIS and 651 randomly selected control women completed in-person
      interviews. The presence of HPV DNA in archival ACIS specimens was determined by
      E6 and L1 consensus PCR. Serum samples from case and control subjects were
      collected at interview, and antibodies to HPV-16 L1 and HPV-18 L1 were detected
      by virus-like particle capture assays. The overall prevalence of HPV DNA was
      86.6%, with 39.0% positive for HPV-16 DNA, 52.4% positive for HPV-18 DNA, and
      13.4% positive for more than one HPV type. The age-adjusted relative risk of ACIS
      associated with HPV-18 seropositivity was 3.3 (95% confidence interval 2.2-4.9).
      No increased risk was associated with antibodies to HPV-16 L1. Among women born
      after 1945, the relative risk increased with duration of OC use, with the highest
      risk for 12 or more years of use (odds ratio, 5.5; 95% confidence interval, 2.1
      14.6) relative to nonusers. The detection of HPV DNA in 86.6% of ACIS and the
      strong association of ACIS with HPV-18 L1 seropositivity underscore the
      importance of HPV, particularly HPV-18, in the etiology of ACIS. In addition,
      long-term OC use may contribute to the pathogenesis of these tumors in some
      women.

PMID- 11303585
TI  - Effect of soymilk consumption on serum estrogen and androgen concentrations in
      Japanese men.
AB  - Soy consumption has been associated with a reduced risk of prostate cancer. The
      mechanism for this association may involve the effect of soy on the endocrine
      system. We conducted a randomized dietary intervention study to determine the
      effects of soy consumption on serum levels of steroid hormones in men. Thirty
      five men were randomly assigned to either a soymilk-supplemented group or a
      control group. The men in the soy-supplemented group were asked to consume 400 ml
      of soymilk daily for 8 weeks. The men in the control group maintained their usual
      diet. Blood samples were obtained just before the initiation of the dietary
      period and thereafter every two weeks for 12 weeks. Changes in hormone
      concentrations were analyzed and compared between the two groups using the mixed
      linear regression model against weeks from the start of the dietary period. The
      mean (SD) soymilk intake estimated from dietary records during the dietary study
      period was 342.9 (SD, 74.2) ml in the soymilk-supplemented group. There was a
      significant difference between the two groups in terms of changes in serum
      estrone concentrations, which tended to decrease in the soy-supplemented group
      and increase in the control group over time. None of the other hormones measured
      (estradiol, total and free-testosterone, or sex hormone-binding globulin) showed
      any statistical difference between the two groups in terms of patterns of change.
      The results of the study indicate that soymilk consumption may modify circulating
      estrone concentrations in men.

PMID- 11303586
TI  - The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2)
      genes and serum androgen concentrations in men.
AB  - Prospective studies suggest that prostate cancer risk may be increased in
      association with high serum concentrations of free testosterone and
      androstanediol glucuronide (A-diol-g). Polymorphisms have been identified in the
      17-hydroxylase cytochrome P450 gene (CYP17) and the steroid 5alpha-reductase type
      II gene (SRD5A2), two genes that are involved in the biosynthesis and metabolism
      of androgens in men. The CYP17 MspA1 I polymorphism has been associated with
      increased prostate cancer risk, and the SRD5A2 V89L polymorphism has been
      associated with low A-diol-g in Asian men, a serum marker of 5alpha-reductase
      activity. The purpose of this study was to investigate the association between
      these two polymorphisms and serum sex hormone concentrations in 621 British men.
      In particular, we wanted to test the hypotheses that the A2 allele in the CYP17
      gene is associated with increased serum testosterone concentrations, and the L
      allele in the SRD5A2 gene is associated with reduced A-diol-g concentrations.
      Mean hormone concentrations were evaluated in each genotype and adjusted for age
      and other relevant factors. We found no evidence that the CYP17 MspA1 I
      polymorphism was associated with higher testosterone levels. The L/L genotype of
      the SRD5A2 V89L polymorphism was associated with a 10% lower A-diol-g
      concentration, but this was not significant at the 5% level. However, the L/L
      genotype of the V89L polymorphism was associated with significantly lower
      concentrations of testosterone and free testosterone (by 12% and 16%,
      respectively) and an 8% higher sex hormone-binding globulin concentration. These
      results suggest that the CYP17 MspA1 I polymorphism is not associated with
      testosterone concentrations and that the SRD5A2 V89L polymorphism is not a strong
      determinant of A-diol-g concentration in Caucasian men.

PMID- 11303587
TI  - Alpha-difluoromethylornithine induction of apoptosis: a mechanism which reverses
      pre-established cell proliferation and cancer initiation in esophageal
      carcinogenesis in zinc-deficient rats.
AB  - Alpha-difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine
      decarboxylase, the first enzyme in polyamine synthesis. Previous work showed
      simultaneous administration of DFMO and a zinc-deficient (ZD) diet to weanling
      rats from the beginning inhibited the onset of zinc-deficiency-induced esophageal
      cell proliferation by activating apoptosis and reduced the incidence of N
      nitrosomethylbenzylamine (NMBA)-induced esophageal cancer. Because esophageal
      cancer initiation by NMBA is very rapid in ZD rats, this study determined whether
      DFMO is effective in preventing esophageal carcinogenesis when administered after
      the establishment of a carcinogenic environment. Weanling rats were given a ZD
      diet for 5 weeks to establish sustained increased esophageal cell proliferation
      and then an intragastric dose of NMBA. Thereafter, 20 rats were switched to DFMO
      containing water while nine control ZD animals remained on deionized water; all
      of the animals continued on the ZD diet. Esophagi were collected 15 weeks later.
      The upper portion was processed for immunohistochemical analysis of cell
      proliferation, apoptosis, and expression of related genes, and the lower was
      processed for polyamine content. DFMO substantially reduces the levels of
      esophageal putrescine and spermidine and esophageal tumor incidence from 89 to
      10% in ZD rats. Importantly, DFMO-treated ZD esophagi display increased rate of
      apoptosis accompanied by intense bax expression and greatly reduced cell
      proliferation by proliferating cell nuclear antigen expression. In addition, the
      p16(ink4a)/retinoblastoma control at G1 to S, deregulated in ZD esophagi, is
      restored after DFMO treatment. These results demonstrate that DFMO, a highly
      effective chemopreventive agent in esophageal carcinogenesis, reverses and
      counteracts esophageal cell proliferation/cancer initiation in ZD animals by way
      of stimulating apoptosis.

PMID- 11303588
TI  - Oltipraz concentrations in plasma, buccal mucosa cells, and lipids:
      pharmacological studies.
AB  - Oltipraz is considered one of the most potent cancer chemoprevention agents, as
      shown in preclinical studies. Its pharmacological effects in humans have been
      associated with unusual toxicity affecting the fingers and toes. This study was
      designed to test intermittent dosing schedules using two dosage levels: 500 mg as
      a single weekly dose and 200 mg as a biweekly dose, each for 30 days. Fifteen men
      and women were studied in each dosing group. All were heavy smokers considered to
      be at high risk for developing lung cancer. Plasma, buccal mucosa cell, and
      lipoprotein concentrations were measured at different intervals corresponding to
      the time period when most of the adverse effects occur. No serious toxicities
      were observed using these doses and schedules. The plasma and buccal mucosa cell
      concentrations of Oltipraz showed substantial interindividual variations at each
      sampling. Some subjects had no detectable plasma or buccal mucosal cell Oltipraz
      concentrations. The distribution of Oltipraz incorporation into the lipid
      fractions and albumin was changed by the administration of different schedules of
      Oltipraz. The results of this study suggest that the intermittent dosing is well
      tolerated and does not result in steady state in plasma or buccal mucosa cells.
      The variation and lack of detectable Oltipraz concentration in plasma, buccal
      mucosa cells, and lipids may affect both the toxicity and the pharmacological
      effects when these doses and schedules are used.

PMID- 11303589
TI  - Case-control study of ovarian cancer and polymorphisms in genes involved in
      catecholestrogen formation and metabolism.
AB  - Steroid hormones, such as estrogens, appear to be associated with ovarian
      carcinogenesis, but the precise biological mechanisms are unclear. Polymorphisms
      in genes that regulate the concentration of estrogens and their metabolites may
      contribute directly to the individual variation in ovarian cancer risk through a
      mechanism involving oxidative stress or indirectly by influencing ovarian cancer
      susceptibility associated with ovulation and reproduction. We conducted a
      population-based, case-control study of primary ovarian cancer between 1993 and
      1999 in Hawaii to test several genetic and related hypotheses. A personal
      interview and blood specimen were obtained in the subjects' homes. In a sample of
      129 epithelial ovarian cancer cases and 144 controls, we compared the frequencies
      of several polymorphisms in genes that regulate steroid hormone metabolism and
      catecholestrogen formation. Multivariate unconditional logistic regression was
      used to model the association of each genetic polymorphism separately after
      adjusting for age, ethnicity, and other covariates. The high-activity Val432
      allele of the CYP1B1 gene, which may be linked to oxidative stress through
      elevated 4-hydroxylated catecholestrogen formation, was associated with an
      increased risk of ovarian cancer. The Val/Leu genotype for CYP1B1 was associated
      with an odds ratio of 1.8 (95% confidence interval, 1.0-3.3) and the Val/Val
      genotype with an odds ratio of 3.8 (95% confidence interval, 1.2-11.4) compared
      with the Leu/Leu genotype (P = 0.005). Tobacco smokers with at least one CYP1A1
      (MspI) m2 allele, one CYP1B1 Val allele, one COMT Met allele, or two CYP1A2 A
      alleles were at significantly increased risk of ovarian cancer compared to never
      smokers with CYP1A1 (MspI) ml/ml, CYP1B1 Leu/Leu, COMT Val/Val, or CYP1A2 A/A
      genotypes, respectively. We found a positive statistical interaction (P = 0.03)
      between tobacco smoking and the CYP1A1 (MspI) polymorphism on the risk of ovarian
      cancer. None of the other gene-environment (pregnancy, oral contraceptive pill
      use) or gene-gene interactions were statistically significant. Although not
      significant, there was a suggestion that the effect of the CYP1B1 Val allele was
      reduced substantially in the presence of the high-activity COMT Met allele. These
      findings suggest that the CYP1B1-Val allele and perhaps other genetic
      polymorphisms in combination with environmental or hormonal exposures are
      susceptibility factors for ovarian cancer.

PMID- 11303590
TI  - Polymorphisms in the DNA repair gene XRCC1 and breast cancer.
AB  - X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in
      base excision repair. We examined the association of polymorphisms in XRCC1
      (codon 194 Arg-->Trp and codon 399 Arg-->Gln) and breast cancer in the Carolina
      Breast Cancer Study, a population-based case-control study in North Carolina. No
      association was observed between XRCC1 codon 194 genotype and breast cancer, and
      odds ratios (ORs) were not modified by smoking or radiation exposure. A positive
      association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with
      Arg/Arg was found among African Americans (253 cases, 266 controls; OR = 1.7, 95%
      confidence interval, 1.1-2.4) but not whites (386 cases, 381 controls; OR =1.0,
      95% confidence interval, 0.8-1.4). Among African-American women, ORs for the
      duration of smoking were elevated among women with XRCC1 codon 399 Arg/Arg
      genotype (trend test; P < 0.001) but not Arg/Gln or Gln/Gln (P = 0.23). There was
      no difference in OR for smoking according to XRCC1 codon 399 genotype in white
      women. ORs for occupational exposure to ionizing radiation were stronger for
      African-American and white women with codon 399 Arg/Arg genotype. High-dose
      radiation to the chest was more strongly associated with breast cancer among
      white women with XRCC1 codon 399 Arg/Arg genotype. Our results suggest that XRRC1
      codon 399 genotype may influence breast cancer risk, perhaps by modifying the
      effects of environmental exposures. However, interpretation of our results is
      limited by incomplete knowledge regarding the biological function of XRCC1
      alleles.

PMID- 11303591
TI  - Urinary phytoestrogens and postmenopausal breast cancer risk.
AB  - Phytoestrogens are defined as plant substances that are structurally or
      functionally similar to estradiol. We report the associations of two major
      phytoestrogens, genistein and enterolactone, with breast cancer risk, using
      urinary specimens collected 1-9 years before breast cancer was diagnosed. The
      subjects were 88 breast cancer cases and 268 controls, selected from a cohort of
      postmenopausal women (n = 14,697) who participated in a breast cancer screening
      program. Mean levels of urinary genistein and enterolactone were determined by
      time resolved fluoroimmunoassay, using an average of two overnight urinary
      samples obtained from each participant on the first and the second screening
      rounds with a time interval of approximately 1 year. Odds ratios (ORs) of the
      highest to the lowest tertile of urinary phytoestrogen/creatinine concentrations
      and 95% confidence intervals (CIs) were computed. Higher urinary genistein
      excretion was weakly and nonsignificantly associated with a reduced breast cancer
      risk. OR for the highest tertile compared with lowest tertile was 0.83; 95% CI,
      0.46-1.51. Higher urinary enterolactone excretion was weakly and nonsignificantly
      associated with an increased breast cancer risk. OR for the highest tertile
      compared with the lowest tertile was 1.43; 95% CI, 0.79-2.59. Tests for trends
      for both phytoestrogens were nonsignificant. We were not able to detect the
      previously reported protective effects of genistein and enterolactone on breast
      cancer risk in our postmenopausal population of Dutch women. Such an effect may
      be smaller than expected and/or limited to specific subgroups of the population.

PMID- 11303592
TI  - Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and
      susceptibility to breast cancer.
AB  - This study was undertaken to examine if glutathione S-transferase (GST) M1, M3,
      P1, and T1 genotypes affected breast cancer risk in Finnish women. The study
      population consisted of 483 incident breast cancer cases and 482 healthy
      population controls. Genotyping analyses were performed by PCR-based methods, and
      odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by
      unconditional logistic regression adjusting for known or suspected risk factors
      for breast cancer. When the genes were studied separately, the only significant
      finding was between GSTM1 null genotype and postmenopausal breast cancer risk
      (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of
      the at-risk genotypes were examined, significant associations were observed only
      among premenopausal women. Although only a moderate risk of breast cancer was
      seen for premenopausal women concurrently carrying the GSTM3*B allele containing
      genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk
      rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10
      90.0). A borderline significant increase in the risk of breast cancer was also
      seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile,
      and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the
      view that GST genotypes contribute to the individual breast cancer risk,
      especially in certain combinations.

PMID- 11303593
TI  - Epidemiological study of urinary 6beta-hydroxycortisol to cortisol ratios and
      breast cancer risk.
AB  - The ratio of urinary 6beta-hydroxycortisol:cortisol is a measure of the activity
      of cytochrome p450 3A4 (CYP3A4). CYP3A4 catalyzes the formation of the genotoxic
      estrogen, 16alpha-hydroxyestrone. It is also involved in the activation of many
      other mammary carcinogens, such as the polycyclic aromatic hydrocarbons and
      heterocyclic amines. We evaluated the association between urinary cortisol ratios
      and breast cancer risk in a subgroup of women who participated in a population
      based case-control study in Shanghai. Overnight urine samples from 246 case
      control pairs were assayed for 6beta-hydroxycortisol (6beta-OHC) to cortisol. The
      urine samples from all of the breast cancer patients were collected before any
      chemotherapy or radiotherapy. In-person interviews were conducted to obtain
      comprehensive information on dietary habits, reproductive history, and other
      lifestyle factors. The median levels of 6beta-OHC:cortisol ratios were 2.61 in
      cases and 2.16 in controls, a 20.8% difference (P < 0.001). The case-control
      difference was larger in women over 45 years of age (31.3% difference; P < 0.001)
      than younger women (6.0%; P = 0.45). After adjusting for confounding variables,
      the risks of breast cancer were increased from 1.0 (reference) to 1.6 [95%
      confidence interval (CI), 0.9-3.1], 2.2 (95% CI, 1.1-4.2), and 3.7 (95% CI, 1.9
      7.4; P for trend, <0.001) with increasing levels of 6beta-OHC:cortisol ratios.
      The positive association was more pronounced among older women (>45 years) than
      among younger women (< or = 45 years). The adjusted odds ratios associated with
      the highest cortisol ratio were 6.0 (95%CI, 2.2-16.1) among older women and 2.2
      (95%CI, 0.8-6.1) among younger women. The association of the 6beta-OHC:cortisol
      ratio was stronger among older women who had a high body mass index, late age at
      menopause, and early age at menarche (factors related to high endogenous estrogen
      exposure) than those who did not have these factors. These findings are
      consistent with the role of CYP3A4 in estrogen and carcinogen metabolism and
      suggest that high CYP3A4 activity may be a risk factor for breast cancer risk.

PMID- 11303594
TI  - Growth factors and stromal matrix proteins associated with mammographic
      densities.
AB  - Extensive radiologically dense breast tissue is associated with a marked increase
      in breast cancer risk. To explore the biological basis for this association, we
      have examined the association of growth factors and stromal matrix proteins in
      breast tissue with mammographic densities. Ninety-two formalin-fixed paraffin
      blocks of breast tissues surrounding benign lesions were obtained, half from
      breasts with little or no density and half from breasts with extensive density,
      matched for age at biopsy. Sections were stained for cell nuclei, total collagen,
      the stromal matrix regulatory protein tissue metalloproteinase-3 (TIMP-3), and
      the growth factors, transforming growth factor-alpha and insulin-like growth
      factor (IGF-I). The area of immunoreactive staining was measured using
      quantitative microscopy. Breast tissue from subjects with extensive densities had
      a greater nuclear area (P = 0.007), as well as larger stained areas of total
      collagen (P = 0.003), TIMP-3 (P = 0.08), and IGF-I (P = 0.02) when compared with
      subjects with little breast density. Differences were greater for subjects less
      than 50 years of age. These data indicate that increased tissue cellularity,
      greater amounts of collagen, and increased IGF-I and TIMP-3 expression are found
      in tissue from mammographically dense breasts and suggest mechanisms that may
      mediate the associated increased risk of breast cancer.

PMID- 11303595
TI  - Quantitative nuclear morphometry by image analysis for prediction of recurrence
      of ductal carcinoma in situ of the breast.
AB  - Clinical management of ductal carcinoma in situ (DCIS) remains a challenge
      because significant proportions of patients experience recurrence after
      conservative surgical treatment. Unfortunately, it is difficult to prospectively
      identify, using objective criteria, patients who are at high risk of recurrence
      and might benefit from additional treatment. We conducted a multi-institutional,
      collaborative case-control study to identify nuclear morphometric features that
      would be useful for identifying women with DCIS at the highest risk of
      recurrence. Tissue sections of archival breast tissue of 29 women with recurrent
      and 73 matched women with nonrecurrent DCIS were stained for DNA, and nuclei in
      the DCIS lesions were evaluated by image analysis. A clear correlation between
      mean fractal2_area (FA2) and nuclear grade was observed (P < 0.001), allowing an
      objective determination of nuclear grade. Several nuclear morphometric features,
      including mean and variance of variation of radius, mean area, mean and variance
      of frequency of high boundary harmonics (FQH), and variance in sphericity, were
      found to be useful in discriminating recurrent from nonrecurrent DCIS subjects.
      However, the nuclear features associated with recurrence differed between high-
      and low-grade lesions. For lesions with high FA2 (nuclear grade 3), mean
      variation of radius, mean FQH, and mean area alone yielded recurrence odds ratios
      of 4.55 [95% confidence interval (CI) 0.45-45.96], 3.86 (95% CI, 0.88-16.98),
      2.90 (95% CI, 0.31-27.2), respectively. Using a summed feature model, high-FA2
      lesions showing three poor prognostic features had an odds ratio of 15.63 (95%
      CI, 1.22-200), compared with those with zero or one poor prognostic feature.
      Lesions with low mean FA2 (nuclear grade 1 or 2) showing high variances in
      sphericity and FQH had an odds ratio of 7.71 (95% CI, 1.77-33.60). Addition of
      other features did not enhance the odds ratio or its significance. These results
      suggest that nuclear image analysis of DCIS lesions may provide an adjunctive
      tool to conventional pathological analysis, both for the objective assessment of
      nuclear grade and for the identification of features that predict patient
      outcome.

PMID- 11303596
TI  - Nicotine metabolism and CYP2D6 phenotype in smokers.
AB  - We tested the hypothesis that the polymorphic enzyme CYP2D6 is related to
      nicotine metabolism in 261 healthy subjects enrolling in a smoking cessation
      clinic. Subjects completed a questionnaire, were given dextromethorphan, and
      contributed a urine and blood sample. The CYP2D6 phenotype (based on a
      determination of dextromethorphan and metabolites in an aliquot of overnight
      urine) and genotype (based on characterization of CYP2D6 variant alleles by a PCR
      based method on a subset) were determined. Seventeen poor metabolizers (6.5%)
      were observed among 261 phenotyped smokers. Nicotine and it chief metabolites,
      cotinine and trans-3'-hydroxycotinine were measured in the urine and adjusted for
      pH. All of the nicotine metabolite levels were significantly related to usual and
      recent smoking. Neither levels of smoking nor nicotine metabolites overall
      exhibited a relationship to the CYP2D6-deficient metabolizer phenotype. The ratio
      of nicotine:cotinine + trans-3'-hydroxycotinine, stratified by time since the
      last cigarette, was unrelated to gender, age, education, race (white/African
      American), recent alcohol or caffeine consumption, or smoking practices. Subjects
      in either the lowest quintile or decile metabolic ratio (ultrametabolizers)
      exhibited a significantly lower nicotine:cotinine + trans-3'-hydroxycotinine
      ratio after adjustment for recent smoking, pH, and other factors. These data
      suggest that the polymorphic CYP2D6 gene is not a major contributor to nicotine
      metabolism in tobacco smokers but may influence the disposition of nicotine in
      the small subset of the population who are CYP2D6 ultrametabolizers.

PMID- 11303597
TI  - Physical activity in relation to cancer of the colon and rectum in a cohort of
      male smokers.
AB  - We examined the association between occupational and leisure physical activity
      and colorectal cancer in a cohort of male smokers. Among the 29,133 men aged 50
      69 years in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study,152 colon
      and 104 rectal cancers were documented during up to 12 years of follow-up. For
      colon cancer, compared with sedentary workers, men in light occupational activity
      had a relative risk (RR) of 0.60 [95% confidence interval (CI), 0.34-1.04],
      whereas those in moderate/heavy activity had an RR of 0.45 (CI, 0.26-0.78; P for
      trend, 0.003). Subsite analysis revealed a significant association for
      moderate/heavy occupational activity in the distal colon (RR, 0.21; CI, 0.09
      0.51) but not in the proximal colon (RR, 0.87; CI, 0.40-1.92). There was no
      significant association between leisure activity and colon cancer (active versus
      sedentary; RR, 0.82; CI, 0.59-1.13); however, the strongest inverse association
      was found among those most active in both work and leisure (RR, 0.33; CI, 0.16
      0.71). For rectal cancer, there were risk reductions for those in light (RR,
      0.71; CI, 0.36-1.37) and moderate/heavy occupational activity (RR, 0.50; CI, 0.26
      0.97; P for trend, 0.04), and no association for leisure activity. These data
      provide evidence for a protective role of physical activity in colon and rectal
      cancer.

PMID- 11303598
TI  - Phase I/pharmacodynamic study of N-acetylcysteine/oltipraz in smokers: early
      termination due to excessive toxicity.
AB  - An N-acetylcysteine (NAC)/oltipraz (OLZ) combination was studied in healthy
      volunteer smokers who received daily NAC (1200 mg/day) and were randomized to
      weekly placebo (Arm A), OLZ 200 mg (Arm B), or 400 mg (Arm C). Treatment was for
      12 weeks with follow-up at 16 weeks. The objective was to study toxicity and the
      modulation of pharmacodynamic end points. After treatment of 19 of a planned 60
      subjects, (Arm A, six; Arm B, four; and Arm C, nine), the study was closed
      because of toxicity. Eight subjects failed to complete 12 weeks of drug
      administration, (Arm A, two, and Arm C, six). The most frequent side effects were
      gastrointestinal, fatigue, conjunctival irritation, and skin rash.
      Pharmacodynamic end points were measured pretreatment and 48 h after the dose of
      OLZ at weeks 1, 5, and 12 and 4 weeks after the end of treatment. Glutathione
      (GSH) was measured in plasma and in peripheral blood lymphocytes (PBLs). Other
      end points measured in PBLs were the enzyme activities of total glutathione-S
      transferase (GST), GSTpi, and NAD(P)H:quinone oxidoreductase; and the mRNA
      expression of gamma-glutamylcysteine synthetase gammaGCS), GSTpi, and
      NAD(P)H:quinone oxidoreductase. GSH in PBLs, GST (total), and the mRNA of
      gammaGCS showed increases at some time points in some subjects. Most consistent
      was the mRNA of gammaGCS, which showed a > or = 30% increase at one or more time
      points in 11 of 19 subjects. Other end points were unchanged. We concluded that
      NAC/OLZ modulates some end points related to GSH but is too toxic for
      chemoprevention at the doses used.

PMID- 11303600
TI  - An intronic variant in PTEN is not associated with prostate cancer risk.

PMID- 11303599
TI  - Alcohol dehydrogenase 3 genotype is not associated with risk of squamous cell
      carcinoma of the oral cavity and pharynx.
AB  - Alcohol is one of the major risk factors for oral and pharyngeal cancer. The rate
      limiting step in alcohol metabolism is the oxidation (activation) of ethanol to
      acetaldehyde by the alcohol dehydrogenases (ADHs). It has been hypothesized that
      individuals who are homozygous for the fast allele (ADH(1-1)(3)) are at greater
      risk for alcohol-related cancers. To test this hypothesis, we investigated the
      association between the ADH3 genotype and oral and pharyngeal cancer risk in a
      large racially homogeneous case-control study of 229 patients and 575 matched
      control subjects with frequency matching on age, sex, and smoking status.
      Although the smoking status was matched between cases and controls, current and
      former alcohol use remained a significant risk factor, compared with never use
      (odds ratio, 2.08; 95% confidence interval, 1.37-3.17; odds ratio, 1.97; 95%
      confidence interval, 1.25-3.09; and odds ratio, 1.00, respectively). The ADH1(3)
      allele frequency of controls was 57.4%, consistent with reports of similar racial
      groups (50-60%). The genotype distribution in controls was also consistent with
      the Hardy-Weinberg equilibrium (P = 0.51). However, the ADH1(3) allele frequency
      and ADH(1-1)(3) genotype frequency were not significantly different between cases
      and controls [55.5% versus 57.4% (P = 0.52), and 30.6% versus 31.3% (P = 0.91),
      respectively]. There was no association between ADH3 genotypes (ADH(1-1)(3),
      ADH(1-2)(3), and ADH(2-2)(3)) and risk of oral and pharyngeal cancer (odds
      ratios, 1.00; 0.96; 95% confidence interval, 0.68-1.37; and odds ratio, 1.23;
      confidence interval, 0.78-1.93, respectively). Therefore, we found no evidence
      that supports a main effect of ADH3 genotype or a combined effect of alcohol and
      ADH3 genotype on risk of cancer of the oral cavity or pharynx.

PMID- 11303601
TI  - Support ventilation versus conventional oxygen.

PMID- 11303602
TI  - Support ventilation versus conventional oxygen.

PMID- 11303603
TI  - Management of peanut and nut allergy.

PMID- 11303604
TI  - Atrial fibrillation control and cardioversion.

PMID- 11303605
TI  - Neonatal necropsy.

PMID- 11303606
TI  - High-dose cyclophosphamide in aplastic anaemia.

PMID- 11303607
TI  - Streptococcus infection and splenectomy.

PMID- 11303608
TI  - Streptococcus infection and splenectomy.

PMID- 11303609
TI  - Streptococcus infection and splenectomy.

PMID- 11303610
TI  - Pharmacological strategies for blood loss.

PMID- 11303611
TI  - Call for global snake-bite control and procurement funding.

PMID- 11303612
TI  - Call for global snake-bite control and procurement funding.

PMID- 11303613
TI  - What's in a name.

PMID- 11303614
TI  - What's in a name.

PMID- 11303615
TI  - What's in a name.

PMID- 11303616
TI  - What's in a name.

PMID- 11303617
TI  - Updating the WHO essential drugs list.

PMID- 11303618
TI  - Scalp cooling therapy and cytotoxic treatment.

PMID- 11303619
TI  - Antitumor activity of a human cytotoxic T-cell line (TALL-104) in brain tumor
      xenografts.
AB  - Malignant glioma in adults and primitive neuroectodermal tumors/medulloblastomas
      in children are the most common malignant primary brain tumors that either
      respond poorly to current treatment or tend to recur. Adoptive therapy with TALL
      104 cells-an IL-2-dependent, major histocompatibility complex nonrestricted,
      cytotoxic T-cell line-has demonstrated significant antitumor activity against a
      broad range of implanted or spontaneously arising tumors. This study investigates
      distribution of systemically and locally administered TALL-104 cells and their
      efficacy in effecting survival of a rat model of human brain tumor. In vitro,
      TALL-104 cells showed significant cytotoxic activity when added to human
      glioblastoma cell lines U-87 MG, U-251 MG, and A1690; the medulloblastoma cell
      lines DAOY, D283 Med, and D341 Med; and the epidermoid cancer cell line A431. In
      brain tumor-bearing rats, the amount of fluorescent dye-labeled TALL-104 cells in
      brain increased after they were given by intracarotid injection as compared with
      i.v. cell administration. However, TALL-104 cells rapidly decreased to low levels
      within 1 h after intracarotid injection. This finding suggests that TALL-104
      cells given systemically may not invade brain or tumor tissues, but rather may
      remain in the vascular system, making this approach less efficient for brain
      tumor treatment. In a model of athymic rats engrafted with human A431 carcinoma
      brain tumor, repetitive local administration of TALL-104 cells directly into the
      tumor bed resulted in a significant increase in survival time compared with
      control animals. Therefore, local therapy with TALL-104 cells may be a novel and
      highly effective treatment approach for malignant brain tumors.

PMID- 11303620
TI  - Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.
AB  - The objective of this study was to ascertain the duration of tumor control and
      the toxicities of dose-intense myeloablative chemotherapy for patients with
      recurrent oligodendrogliomas. Patients with previously irradiated
      oligodendrogliomas, either pure or mixed, that were contrast enhancing,
      measurable, and behaving aggressively at recurrence were eligible for this study.
      Only complete responders or major partial responders (75 % reduction in tumor
      size) to induction chemotherapy--either intensive-dose procarbazine, lomustine,
      and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300
      mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone
      marrow or peripheral blood stem cells. Thirty-eight patients began induction
      chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky
      score 80) received high-dose thiotepa. For the high-dose group, the median event
      free, progression-free, and overall survival times from recurrence were 17, 20,
      and 49 months, respectively. Tumor control in excess of 2 years was observed in 6
      patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months
      (median, 42 months) from the start of induction therapy; however, fatal treatment
      related toxicities also occurred in 4 patients (20%). Three patients died as a
      result of a progressive encephalopathy which, in 2 instances, was accompanied by
      a wasting syndrome; 1 patient died as a consequence of an intracerebral
      (intratumoral) hemorrhage. Fatal toxicities occurred in patients with
      pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate
      response was a disappointing treatment strategy for patients with recurrent
      aggressive oligodendroglial neoplasms, although several patients had durable
      responses. Moreover, as prescribed, high-dose thiotepa had significant toxic
      effects in previously irradiated patients, especially those with poorer
      performance status.

PMID- 11303621
TI  - Lack of association of rare alleles in the HRAS variable number of tandem repeats
      (VNTR) region with adult glioma.
AB  - HRAS rare alleles have been associated with the increased susceptibility to a
      variety of cancers. In the present study we examined the hypothesis that HRAS
      rare alleles are a risk factor for adult glioma in a population-based case
      control study of adult glioma in six San Francisco Bay Area counties. We compared
      the prevalence of rare alleles in the variable number of tandem repeats region of
      HRAS in the germline DNA from 73 white adults who had gliomas with that of 65
      controls. Overall, the prevalence of rare alleles in cases was not different from
      the prevalence of those in controls according to two definitions of rare alleles.
      We found that 25 of 73 (34%) of cases versus 25 of 65 (38%) of controls had at
      least one allele that was not 30, 46, 69, or 87 repeats; 4 of 73 (5%) of cases
      versus 6 of 65 (9%) of controls carried one or more alleles with 33, 39, 42, 53,
      59, 63, 68, 105, or 114 repeats. The proportion of rare alleles was somewhat
      higher among subjects with anaplastic astrocytoma. Among women, cases were less
      likely than controls to have HRAS rare alleles, whereas among men, cases were
      slightly more likely to have HRAS rare alleles, but none of these results
      approach statistical significance. Our data do not suggest an excess of HRAS rare
      alleles among adult glioma cases.

PMID- 11303622
TI  - A patient's plea--breaking the news.

PMID- 11303623
TI  - Immunocytochemical mapping of the phosphatase and tensin homolog (PTEN/MMAC1)
      tumor suppressor protein in human gliomas.
AB  - PTEN/MMAC1 (phosphatase and tensin homolog/mutated in multiple advanced cancers
      1) is a tumor suppressor gene, the inactivation of which is an important step in
      the progression of gliomas to end-stage glioblastoma multiforme. We examined the
      distribution of PTEN protein in 49 primary human gliomas by immunocytochemistry
      using polyclonal antibodies that we raised against PTEN-glutathione S-transferase
      fusion proteins expressed in Escherichia coli. The study group consisted of 6 low
      grade astrocytomas, 7 anaplastic astrocytomas, 21 glioblastomas multiforme, 4 low
      grade oligodendrogliomas, 6 malignant oligodendrogliomas, and 5 malignant mixed
      oligoastrocytomas. For each tumor, we determined the percentage of tumor cells
      showing PTEN immunoreactivity in the most cellular regions of the tumor specimen.
      In both astrocytomas and oligodendrogliomas, there was an inverse relationship
      between the percentage of PTEN+ cells and malignancy grade, consistent with a
      role for PTEN as a tumor suppressor gene, the expression of which declines during
      glioma progression. In nonneoplastic tissue, PTEN was expressed in human fetal
      brain at 16, 23, and 27 weeks' gestation, but not in adult brain, indicating that
      PTEN is developmentally regulated in the CNS. In 21 glioblastomas multiforme, we
      correlated PTEN protein expression with PTEN gene sequence. Although PTEN-mutant
      tumors showed significantly diminished PTEN protein expression compared with wild
      type cases, suppressed expression of PTEN is more prevalent than predicted from
      mutation frequencies.

PMID- 11303625
TI  - Quantification of microheterogeneity in glioblastoma multiforme with ex vivo high
      resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy.
AB  - Microheterogeneity is a routinely observed neuropathologic characteristic in
      brain tumor pathology. Although microheterogeneity is readily documented by
      routine histologic techniques, these techniques only measure tumor status at the
      time of biopsy or surgery and do not indicate likely tumor progression. A
      biochemical screening technique calibrated against pathologic standards would
      greatly assist in predicting tumor progression from its biological activity. Here
      we demonstrate for the first time that proton magnetic resonance spectroscopy (1H
      MRS) with high-resolution magic-angle spinning (HRMAS), a technique introduced in
      1997, can preserve tissue histopathologic features while producing well-resolved
      spectra of cellular metabolites in the identical intact tissue specimens.
      Observed biochemical alterations and tumor histopathologic characteristics can
      thus be correlated for the same surgical specimen, obviating the problems caused
      by tumor microheterogeneity. We analyzed multiple specimens of a single human
      glioblastoma multiforme surgically removed from a 44-year-old patient. Each
      specimen was first measured with HRMAS 1H MRS to determine tumor metabolites,
      then evaluated by quantitative histopathology. The concentrations of lactate and
      mobile lipids measured with HRMAS linearly reflected the percentage of tumor
      necrosis. Moreover, metabolic ratios of phosphorylcholine to choline correlated
      linearly with the percentage of the highly cellular malignant glioma. The
      quantification of tumor metabolic changes with HRMAS 1H MRS, in conjunction with
      subsequent histopathology of the same tumor specimen, has the potential to
      further our knowledge of the biochemistry of tumor heterogeneity during
      development, and thus ultimately to improve our accuracy in diagnosing,
      characterizing, and evaluating tumor progression.

PMID- 11303624
TI  - Expression of vascular endothelial growth factor-b in human astrocytoma.
AB  - Growth of human malignant gliomas is stringently dependent on an angiogenic
      process that probably involves vascular endothelial growth factor (VEGF).
      Expressions of mRNA coding for the different forms of VEGF were analyzed in
      surgical specimens from human astrocytomas. Low levels of placental growth factor
      (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in
      Northern blot experiments. VEGF mRNA was found in some but not all grade and
      grade IV astrocytomas. VEGFB mRNA was observed in all tissue samples analyzed
      irrespective of the tumor grade. A new splice variant of VEGFB (VEGFB155) that
      lacks exons 5 and 6 is described. Expressions of VEGF mRNA in cultured
      glioblastomas cells were upregulated by hypoxia, but the sensitivity of the cells
      to hypoxia was reduced as compared with normal rat astrocytes. VEGF expression
      was depressed by dexamethasone. Expressions of VEGFB mRNA were affected neither
      by hypoxia nor by dexamethasone. The results indicate a coexpression of VEGF mRNA
      and VEGFB mRNA in human astrocytomas. Expression of VEGFB is markedly different
      from that of VEGF. Possible roles of VEGFB as a cofactor for hypoxia-induced
      angiogenesis in human astrocytomas are discussed.

PMID- 11303626
TI  - A comparative study of apoptosis and proliferation in germinoma and glioblastoma.
AB  - Intracranial germinoma has a relatively good prognosis when treated with
      radiotherapy and chemotherapy, whereas glioblastoma has a poor prognosis
      irrespective of these treatments. Cell proliferation and cell death are opposing
      processes in tumor growth, with tumor progression reflecting the balance between
      proliferating and apoptotic cells. We investigated cell proliferation and cell
      death using MIB-1 staining and nick-end labeling in 13 germinomas in comparison
      with 11 glioblastomas. Expression of BAX and Bcl-2, which regulate apoptosis,
      were studied by immunohistochemistry. Although germinomas showed strong MIB-1
      immunostaining similar to that seen in glioblastomas, germinomas included
      significantly more apoptotic cells. The ratio of apoptotic ratio to MIB-1
      labeling index for germinomas was 72.9 +/- 36.9 (mean +/- SD), a higher,
      statistically significant ratio as compared with glioblastomas (14.5 +/- 11.2; P
      < 0.01). Furthermore, germinomas showed greater expression of BAX than did
      glioblastomas, while the expression of Bcl-2 was weak in both tumor types. A
      comparison of these apoptotic-related proteins showed that immunoreactivity for
      BAX was relatively higher in germinomas than in glioblastomas (P < 0.01),
      corresponding well to numerous apoptotic cells identified in germinoma tissues.
      These findings may account for the prognostic difference between germinoma and
      glioblastoma in the face of a similar proliferation potential according to MIB-1
      immunostaining. The balance between cell proliferation and death should be
      considered when predicting outcomes in patients with intracranial tumors.

PMID- 11303627
TI  - CENP-F gene amplification and overexpression in head and neck squamous cell
      carcinomas.
AB  - BACKGROUND: Antibodies against cancer-related genes have been detected in human
      cancers including head and neck cancers. High titers of c-Myc autoantibodies have
      been linked to gene amplification and tumor progression. Centromere protein-F
      (CENP-F) autoantibodies have been detected in patients with various cancers,
      suggesting similar gene alteration. METHODS: CENP-F and c-MYC amplification was
      assessed in 72 head and neck squamous cell carcinoma (HNSCC) patients. Tumor and
      matched mucosa from 22 patients were analyzed for CENP-F mRNA levels by RT-PCR.
      RESULTS: The larynx was the site most altered by amplification of either gene.
      CENP-F and c-MYC were amplified in 11% and 17% of the tumors, respectively.
      Coamplification was found in 7% of the tumors, most of which showed regional node
      involvement. CENP-F mRNA was overexpressed in 36% of tumors, and 23% of paired
      mucosa. CONCLUSION: Our results provide the first evidence that CENP-F gene is
      amplified and overexpressed in HNSCC. No correlation was noted between CENP-F
      amplification and clinicopathologic parameters. However, CENP-F overexpression
      correlated with nodal metastasis.

PMID- 11303628
TI  - Health-related quality of life three years after diagnosis of head and neck
      cancer--a longitudinal study.
AB  - PURPOSE: To examine health-related quality of life (HRQL) of all head and neck
      cancer patients from diagnosis until 3 years later and to analyze its dependence
      on tumor site and other patient characteristics. SUBJECTS AND METHODS: Two
      hundred thirty-two patients (mean age 61 years; 70% men) were included and
      followed with clinical measures and mailed standardized HRQL questionnaires (The
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core-30 (EORTC QLQ-C30), the EORTC QLQ-Head and Neck Cancer module
      (QLQ-H&N35), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: After
      3 years 66% of the patients were alive and 88% of these completed the study. The
      HRQL was worse during treatment and returned slowly thereafter to pretreatment
      values with few exceptions. After 3 years the best improvement was found for
      mental distress, followed by a significant global quality of life improvement and
      reduced pain compared with diagnosis. A significant deterioration was found for
      problems with dry mouth, senses, and teeth, as well as for opening the mouth wide
      (ie, they seemed to be related to the treatment given). There were few
      significant improvements between the 1- and 3-year follow-ups. Depression and
      physical functioning at diagnosis were independent predictors for global quality
      of life at 3 years. Patients who died during the study had a worse HRQL at
      diagnosis compared with patients completing the study. Patients with advanced
      disease (stage III + IV) scored worse than patients with small tumors for most of
      the HRQL domains. These differences increased over time. Few differences were
      found relating to gender and age. The pharyngeal cancer group scored worse
      compared with the other tumor sites, and these patients would probably benefit
      from a rehabilitation program right from diagnosis, including treatment for
      malnutrition and pain. CONCLUSIONS: The largest HRQL changes for head and neck
      cancer patients are seen within the first year after diagnosis, with a
      significant deterioration just after finishing treatment. Thereafter, most of the
      variables return to pretreatment values. The significant problems with dry mouth,
      senses, and teeth after treatment are constant over time.

PMID- 11303629
TI  - Is conservative treatment of deep neck space infections appropriate?
AB  - BACKGROUND: A 31-patient prospective series on deep neck infections, managed at
      Hospital Ramon y Cajal in Madrid, Spain, is presented. METHODS: A prospective
      study was conducted from January 1994 to December 1997, including all
      parapharyngeal or retropharyngeal infections. Clinical and radiologic findings
      and length of stay in the hospital were registered. Medical treatment was
      instituted with broad-spectrum antibiotics, and surgery was reserved for those
      patients not responding to medical treatment. RESULTS: Twenty-four patients
      (77.42%) had parapharyngeal, 3 (9.68%) retropharyngeal and 4 (12.90%) mixed
      infections. On the basis of clinical and CT findings, 19 cases (61.29%) were
      considered abscesses and 12 (38.71%) cellulitis. Medical treatment was successful
      in all but 3 cases (90.32%), with no major complications. All the patients were
      discharged from the hospital within 20 days after admission (mean, 8.09 days).
      CONCLUSIONS: Despite the wide use of antibiotics, deep neck space infections are
      commonly seen. Although most reports are based on surgical treatment followed by
      antibiotics, medical treatment could be as successful as open surgical drainage
      in most cases.

PMID- 11303630
TI  - The role of hyperplasia in multiple parathyroid adenomas.
AB  - BACKGROUND: Parathyroid adenoma is the most common cause of primary
      hyperparathyroidism (pHPT). Adenomas usually involve only a single gland, and the
      remaining glands are normal or suppressed. Multiple parathyroid adenomas have
      been reported to occur in as high as 11% of patients with pHPT. The significant
      incidence of multiple adenomas with histologic similarities to hyperplasia has
      raised the possibility that adenoma is a continuation of the hyperplasia state.
      To test this theory, we used molecular genetics to compare clonality and
      proliferative activity of parathyroid adenoma with its corresponding normal
      glandular tissue. Furthermore, we devised a scheme to definitively distinguish
      between the different parathyroid states on a molecular level, because histologic
      distinction is unreliable. METHODS: The study included three patients with a
      diagnosis of singular parathyroid adenoma and three with double parathyroid
      adenomas. Paraffin-embedded surgical specimens of both adenomas and normal glands
      were retrieved from each patient. Clonal analysis of the phosphoglycerolkinase
      (PGK) gene has suggested that parathyroid adenomas are monoclonal. Clonality of
      parathyroid adenomas and normal parathyroid glands was studied by polymerase
      chain reaction-based restriction fragment length polymorphic analysis for the PGK
      gene. Proliferative activity of the specimens was also analyzed using the
      immunohistochemical markers PCNA and Ki-67. RESULTS: All adenomas were monoclonal
      and all normal parathyroid glands were polyclonal for the PGK gene in both the
      single and double adenoma specimens. All adenomas stained positive for
      proliferative activity. In the three patients with singular adenoma,
      proliferative activity was not detected in the normal parathyroid tissue.
      However, in the double adenoma group, two of the three patients showed
      hyperproliferative activity in the normal glands. CONCLUSION: Proliferative
      activity consistent with hyperplasia was present in some normal glands of
      multiple adenoma patients. Our observation supports the theory that multiple
      adenomas may be a continuation of the hyperplasia state.

PMID- 11303631
TI  - Outcome after treatment for papillary thyroid cancer.
AB  - BACKGROUND: To evaluate the results of treatment and the prognostic variables of
      papillary thyroid carcinoma patients after long-term follow-up. PATIENTS AND
      METHODS: Retrospective review of 1,373 thyroid cancer patients. Of the 1,016
      papillary thyroid cancer patients, 394 patients received follow-up for more than
      5 years, including 305 women (mean age, 38.4 +/- 13.7 years) and 89 men (mean
      age, 44.0 +/- 13.4 years). Of these papillary thyroid carcinoma patients, 227,
      76, 68, and 23 patients were categorized in clinical stages I, II, III, and IV,
      respectively, at the time of diagnosis. RESULTS: After treatment, 36 (9.1%)
      patients died. Only 23 (5.8%) of them died of papillary thyroid carcinoma. The 1
      , 5-, 10-, and 20-year survival rates were 0.980, 0.951, 0.901, and 0.731.
      Mortality factors of the papillary thyroid carcinoma patients related to age,
      gender, tumor size, and postoperative serum thyroglobulin (Tg) levels. Twenty
      four patients progressed from clinical stages I, II, and III to stage IV during
      the follow-up period. Of these 24 patients, 12 died during the follow-up period.
      In this study, age, gender, 131I accumulated dose, postoperative serum Tg levels,
      and the survival rate were demonstrated to be statistically significant between
      the patients in early stage and advanced stage groups after treatment.
      CONCLUSION: Twenty-four of the 47 papillary thyroid cancer patients with distant
      metastases were diagnosed during the follow-up period. This study suggests that
      distant metastasis may occur at a serum Tg level of 2.3 ng/mL with thyroxine
      replacement. Postoperative long-term close follow-up of these patients is
      recommended.

PMID- 11303632
TI  - Potential molecular prognostic markers in head and neck squamous cell carcinomas.
AB  - BACKGROUND: Current management strategies for squamous cell carcinoma of the head
      and neck (HNSCC) rely on an understanding of the natural history of the disease,
      along with the use of prognostic factors to guide selection of appropriate
      treatment. However, it is recognized that tumor heterogeneity limits the reliable
      use of currently available prognostic markers. With the evolving understanding of
      the genetic and molecular basis of human malignancies, there has been much
      interest in determining whether specific molecular changes in HNSCC might guide
      treatment decisions. METHODS: A literature review of potential molecular markers
      relevant to HNSCC was undertaken and evaluated. It is evident that the published
      information is promising but, oftentimes, limited by a scarcity of large,
      uniformly staged and treated patients, from which the value of novel molecular
      markers can be assessed. RESULTS: On the basis of the review of more than 100
      articles, some of the emerging molecular markers that might provide independent
      prognostic information include epidermal growth factor receptor (EGFR),
      transforming growth factor-alpha (TGF-alpha), cyclin D1, and p53. This review
      will discuss the current status of these molecular factors and consequent
      implications for novel therapeutic approaches for patients with HNSCC.
      CONCLUSION: With the evolving understanding that human malignancies have
      developed and progressed on the basis of accumulated molecular abnormalities,
      there is an existing body of work trying to determine whether such abnormalities
      can predict clinical behavior of HNSCC. Such studies have to be conducted
      rigorously to derive useful information. Nevertheless, the role of such molecular
      markers, and the possibility to exploit them for therapeutic gain, is already at
      the horizon.

PMID- 11303633
TI  - Recurrent nasopharyngeal carcinoma presenting as diffuse dermal lymphatic
      infiltration in the neck: three case reports.
AB  - BACKGROUND: Any malignancy has the propensity to metastasize to skin. The
      frequency of skin metastases vary in different tumors and occur in about 0.7% to
      10% of all patients diagnosed with cancer. It is rare in nasopharyngeal
      carcinoma. METHOD: Three cases of relapsed nasopharyngeal carcinoma with diffuse
      dermal involvement were described. Their clinical presentation, results of
      investigations, and response to treatment were reviewed. Literature review of
      similar forms of presentation was done by means of a MEDLINE search. RESULTS: At
      the time of dermal relapse, all three patients had a uniform clinical picture of
      facial, periorbital, and lip swelling associated with stridor and dysphagia.
      Histologic findings showed dermal infiltrates of malignant cells, and CT scan
      showed diffuse infiltration of the subcutaneous tissue. Despite chemotherapy, the
      clinical course was relentless. CONCLUSION: This report describes a presentation
      of disease that is underdiagnosed and heightens awareness of oncologists to this
      form of recurrence in nasopharyngeal carcinoma.

PMID- 11303634
TI  - Plasma cell variant of Castleman's disease occurring concurrently with Hodgkin's
      disease in the neck.
AB  - BACKGROUND: Castleman's disease, a benign lymphoproliferative disorder, may be
      seen as a self-limited, curable unifocal process, or highly aggressive
      multicentric disease frequently resulting in death despite aggressive management.
      Non-Hodgkin's lymphoma has been known to arise within the context of Castleman's
      disease, usually when multicentric. Hodgkin's lymphoma, however, can also arise
      within the context of Castleman's disease, but this is a rare process. We report
      a case of unifocal Castleman's disease (plasma cell variant) occurring
      concurrently with Hodgkin's disease in the neck of a young woman. METHODS: The
      presentation, workup, pathologic evaluation, and management of a young woman
      diagnosed with Castleman's disease occurring concurrently with Hodgkin's disease
      in the neck is presented and discussed. RESULTS: A 32-year-old woman with a 5
      year history of unifocal right cervicoparotid Castleman's disease (plasma cell
      variant) underwent right functional neck dissection and superficial parotidectomy
      for cosmetic and functional purposes. Pathologic and immunohistochemical analysis
      confirmed Hodgkin's lymphoma occurring in a background of the plasma cell variant
      of Castleman's disease. The patient subsequently underwent external beam
      radiation therapy as definitive management for her early-stage Hodgkin's
      lymphoma. CONCLUSIONS: Castleman's disease can occur as an isolated regional
      process in the head and neck. Furthermore, lymphoma (and specifically Hodgkin's
      lymphoma) can develop within regionally isolated cervical Castleman's disease.
      Although complete surgical excision of unifocal Castleman's disease is curative,
      the management of lymphoma occurring within the context of the Castleman's
      disease warrants a standard lymphoma workup and management strategy.

PMID- 11303635
TI  - Research misconduct.

PMID- 11303636
TI  - Planned neck dissection for advanced primary head and neck malignancy treated
      with organ preservation therapy: disease control and survival outcomes.
AB  - BACKGROUND: The role of planned neck dissection after organ preservation therapy
      with radiotherapy or chemotherapy/radiotherapy for advanced head and neck cancers
      presenting with clinically positive neck disease is still being elucidated. The
      aim of this study is to review the outcomes of such patients treated by organ
      preservation therapy at our institution. METHODS: A retrospective chart review of
      33 patients who underwent planned neck dissections after organ preservation
      therapy for advanced primary head and neck malignancy. Endpoints measured were
      disease-free survival and local, regional, and distant control. SETTING: Tertiary
      metropolitan medical center. RESULTS: Two-year actuarial disease-free survival
      was 61%, and neck control was 92%, with only two failures in the neck. The use of
      neoadjuvant chemotherapy and total dose of radiotherapy did not correlate with
      neck control or disease-free survival. The presence of pathologically positive
      nodal disease at the time of neck dissection did not correlate with recurrent
      neck disease, but was a predictor of local recurrence (p = .0086). CONCLUSIONS:
      Our data suggest that for patients undergoing planned neck dissection after organ
      preservation therapy, neck control is obtained in almost all cases. The presence
      of pathologically positive nodal disease at the time of surgery may have
      implications for the incidence of local recurrence.

PMID- 11303637
TI  - Surgical management of posterior pharyngeal wall carcinomas: functional and
      oncologic results.
AB  - BACKGROUND: The optimal primary treatment for posterior pharyngeal wall tumors
      remains controversial. METHODS: To assess the relevance of surgical treatment
      from a functional and oncologic point of view, we reviewed the cases of 77
      patients surgically treated between 1984 and 1995. Among them 23 had been
      previously irradiated. Fifty-five patients underwent a conservative surgery (CS)
      sparing the larynx; 19 direct closures, 6 reconstructions of the posterior wall
      with a thoracic myocutaneous flap, 15 with a platysma flap, and 15 with a free
      forearm flap were performed. Twenty-two patients underwent radical surgery (RS).
      All previously untreated patients had postoperative radiotherapy. The functional
      assessment concerned the CS group. Oncologic results, especially local control
      and survival were studied for the whole group. RESULTS: Of the 55 patients who
      underwent CS, 53 (96%) had their canula and 49 (89%) their feeding tube removed.
      At 1 year, in the platysma and free forearm groups, 21 of the 24 assessable
      patients were back to exclusive oral intake. For patients treated by primary
      surgery followed by radiotherapy, the rate of local failure was 11% (18% for
      tumors greater than 4 cm), and the 5-year survival rate was 35%. For patients who
      had previous radiotherapy, the rates were, respectively, 52% and 16%. CONCLUSION:
      The satisfactory functional results, caused by the improvement of reconstructive
      procedures, allow conservative surgery even in the case of large tumors.
      Oncologic results, especially local control, suggest that primary surgery
      followed by radiotherapy is effective for the treatment of posterior wall cancer.
      The oncologic results of surgery in a previously irradiated area are poor, and CS
      is not recommended in these cases.

PMID- 11303638
TI  - Markers of neck failure in oral cavity and oropharyngeal carcinomas treated with
      radiotherapy.
AB  - BACKGROUND: Neck management after radiotherapy remains controversial. It is not
      clear which patients may benefit from postradiotherapy neck dissection. Biologic
      markers may be useful in this setting. METHOD: This study includes 81 patients
      with oral cavity and oropharyngeal carcinomas. The primary tumor had been treated
      with radical radiotherapy. Immunohistochemical staining to p53, ki-67, NEU, HSP
      27, and GST has been performed. RESULTS: There were 50 T1-2 and 31 T3-4 patients,
      as well as 36 NO and 45 N1-3. A total of 25 nodal failures was observed. With
      expressed HSP2, 23% of patients had neck failure compared with 51% when HSP-27
      was absent (p = .02). With NEU overexpression, nodal control decreased from 72%
      to 34% (p = .008). In a Cox model, NEU (p = .01) and HSP-27 (p = .05) were
      associated with neck failure. CONCLUSIONS: HSP-27 and NEU expression may play a
      role in predicting nodal failure. This should be confirmed in a larger,
      prospective study.

PMID- 11303639
TI  - F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation
      modality for I-131 scan-negative thyroid carcinoma patients with local recurrence
      in cervical lymph nodes.
AB  - BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG
      PET) has a supplementary role in localizing recurrent sites of differentiated
      thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical
      evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS:
      Preoperative FDG-PET results were compared with the pathologic findings of lymph
      nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy
      and I-131 ablation therapy beforehand and showed negative I-131 scans on follow
      up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node
      groups revealed metastasis. The sensitivity and specificity of FDG PET for
      metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the
      pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET
      detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients
      (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical
      lymph nodes of differentiated thyroid carcinoma patients who showed negative I
      131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.

PMID- 11303640
TI  - Microautoradiographic localization of phosphate and carbohydrates in mycorrhizal
      roots of Populus tremula x Populus alba and the implications for transfer
      processes in ectomycorrhizal associations.
AB  - Microautoradiographic studies were carried out to examine the distribution and
      exchange of phosphate and labeled carbohydrates in mycorrhizal roots of Populus
      tremula x Populus alba L. following application of 33P-orthophosphate (Pi) and
      14CO2. Labeled Pi was not homogeneously distributed along the mycorrhizal
      longitudinal axis. The fungal sheath and the Hartig net contained more 33Pi in
      the median parts of the root than in the apical or basal root zones, indicating
      that uptake and transfer of Pi to the host plant was localized mainly in this
      area. The Pi was translocated by the Hartig net and the interfacial apoplast to
      the host plant. It was distributed by way of the stele within the plant. Young
      leaves and meristematic tissue in the shoot tip were the main sinks for Pi. In
      plants that were left in the dark for 5 days before 33Pi application, the reduced
      carbohydrate supply caused a decrease in Pi absorption by mycorrhizal roots.
      Microautoradiography of mycorrhizal roots after assimilation of 14CO2 revealed
      that: (1) the fungal partner had a high capacity to attract photosynthates; (2)
      the main transfer of carbohydrates was localized in the median zone of a
      mycorrhizal root; (3) carbohydrates that were absorbed by the mycorrhizal fungus
      were translocated to the fungal sheath and were homogeneously distributed; and
      (4) in the main exchange zone, cortical cell nuclei showed a high sink capacity,
      indicating increased metabolic activity in these cells. We postulate that (1) the
      phosphate demand of the host plant regulates absorption of Pi by the fungus, and
      (2) a bidirectional transfer of carbohydrates and Pi occurs across the same
      interface structure in ectomycorrhizal roots of Populus.

PMID- 11303641
TI  - Root system architecture and receptivity to mycorrhizal infection in seedlings of
      Cedrus atlantica as affected by nitrogen source and concentration.
AB  - Effects of nitrogen (N) source and concentration on root system architecture and
      receptivity to mycorrhizal infection were studied in seedlings of Atlas cedar
      (Cedrus atlantica Manetti) grown in root observation boxes in a controlled
      environment chamber. Nitrogen was supplied in a solution containing either NO3-;
      or NH4+ at a concentration of either 0.25 or 5.0 mM. Root extension was recorded
      twice weekly by tracing the roots growing in contact with the transparent face of
      the root observation box. Among treatments, lateral root production and branching
      density were greatest with 5.0 mM NO3-. Inoculation with mycelium of Tricholoma
      cedrorum Malencon was carried out 3 months after the start of the N treatments.
      The highest percentage of mycorrhizal roots, and the greatest amounts of living
      mycelium (estimated by the ergosterol assay) were observed in the NO3-
      treatments. Differences in root branching density among the N treatments were
      insufficient to explain the observed differences among treatments in the extent
      of mycorrhizal infection of seedlings.

PMID- 11303642
TI  - Topology, scaling relations and Leonardo's rule in root systems from African tree
      species.
AB  - Aspects of root architecture, including topology, link length, diameter and
      scaling relations, were analyzed in excavated coarse root systems of three field
      grown fruit tree species (Strychnos cocculoides Bak., Strychnos spinosa Lam. and
      Vangueria infausta Burch) and the fruit-bearing shrub Grewia flava DC. We
      investigated the root systems using semi-automatic digitizing and computer-based
      3-D reconstruction techniques. Topological analysis was carried out to
      investigate branching patterns as basic determinants of root architecture. New
      topological indices were developed and revealed significant differences among the
      species. The different architectural strategies can be explained in terms of cost
      benefit relations and efficiency in soil resource exploration and exploitation.
      In addition, some well-known hypotheses about geometry and scaling, most of them
      previously unverified by empirical observations on root systems, were tested. For
      practical applications, the main emphasis is on the relationship between proximal
      root diameter, an easily determined parameter, and several parameters describing
      the size of the whole root system. We also tested the "pipe stem" theory,
      essentially dating back to Leonardo da Vinci, which underlies many models and
      which we found conformed to our measurement data with reasonable accuracy. A
      physiological consequence of the "constant cross-sectional area rule" may be a
      certain homogeneity of hydraulic architecture throughout root systems.

PMID- 11303643
TI  - Spatial distribution of Eucalyptus roots in a deep sandy soil in the Congo:
      relationships with the ability of the stand to take up water and nutrients.
AB  - Spatial statistical analyses were performed to describe root distribution and
      changes in soil strength in a mature clonal plantation of Eucalyptus spp. in the
      Congo. The objective was to analyze spatial variability in root distribution.
      Relationships between root distribution, soil strength and the water and nutrient
      uptake by the stand were also investigated. We studied three, 2.35-m-wide,
      vertical soil profiles perpendicular to the planting row and at various distances
      from a representative tree. The soil profiles were divided into 25-cm2 grid cells
      and the number of roots in each of three diameter classes counted in each grid
      cell. Two profiles were 2-m deep and the third profile was 5-m deep. There was
      both vertical and horizontal anisotropy in the distribution of fine roots in the
      three profiles, with root density decreasing sharply with depth and increasing
      with distance from the stump. Roots were present in areas with high soil strength
      values (> 6,000 kPa). There was a close relationship between soil water content
      and soil strength in this sandy soil. Soil strength increased during the dry
      season mainly because of water uptake by fine roots. There were large areas with
      low root density, even in the topsoil. Below a depth of 3 m, fine roots were
      spatially concentrated and most of the soil volume was not explored by roots.
      This suggests the presence of drainage channels, resulting from the severe
      hydrophobicity of the upper soil.

PMID- 11303644
TI  - Ammonium and nitrate acquisition by plants in response to elevated CO2
      concentration: the roles of root physiology and architecture.
AB  - We examined changes in root system architecture and physiology and whole-plant
      patterns of nitrate reductase (NR) activity in response to atmospheric CO2
      enrichment and N source to determine how changes in the form of N supplied to
      plants interact with rising CO2 concentration ([CO2]). Seedlings of Betula
      alleghaniensis Britt. and Pinus strobus L., which differ in growth rate, root
      architecture, and the partitioning of NR activity between leaves (Betula) and
      roots (Pinus), were grown in ambient (400 microl l(-1)) and elevated (800 microl
      l(-1)) [CO2] and supplied with either nitrate (NO3-) or ammonium (NH4+) as their
      sole N source. After 15 weeks of growth, plants were harvested and root system
      architecture, N uptake kinetics, and NR activity measured. Betula alleghaniensis
      responded to elevated [CO2] with significant increases in growth, regardless of
      the source of N. Pinus strobus showed no significant response in biomass
      production or allocation to elevated [CO2]. Both species exhibited significantly
      greater growth with NH4+ than with NO3-, along with lower root:shoot biomass
      ratios. Betula showed significant increases in total root length in response to
      elevated [CO2]. However, root N uptake rates in Betula (for both NO3- and NH4+)
      were either reduced or unchanged by elevated [CO2]. Pinus showed the opposite
      response to elevated [CO2], with no change in root architecture, but an increase
      in maximal uptake rates in response to elevated [CO2]. Nitrate reductase activity
      (on a mass basis) was reduced in leaves of Betula in elevated [CO2], but did not
      change in other tissues. Nitrate reductase activity was unaffected by elevated
      [CO2] in Pinus. Scaling this response to the whole-plant, NR activity was reduced
      in elevated [CO2] in Betula but not in Pinus. However, because Betula plants were
      larger in elevated [CO2], total whole-plant NR activity was unaffected.

PMID- 11303645
TI  - Seasonal dynamics of soil carbon dioxide efflux and simulated rhizosphere
      respiration in a beech forest.
AB  - Respiration of the rhizosphere in a beech (Fagus sylvatica L.) forest was
      calculated by subtracting microbial respiration associated with organic matter
      decomposition from daily mean soil CO2 efflux. We used a semi-mechanistic soil
      organic matter model to simulate microbial respiration, which was validated
      against "no roots" data from trenched subplots. Rhizosphere respiration exhibited
      pronounced seasonal variation from 0.2 g C m(-2) day(-1) in January to 2.3 g C m(
      2) day(-1) in July. Rhizosphere respiration accounted for 30 to 60% of total soil
      CO2 efflux, with an annual mean of 52%. The high Q10 (3.9) for in situ
      rhizosphere respiration was ascribed to the confounding effects of temperature
      and changes in root biomass and root and shoot activities. When data were
      normalized to the same soil temperature based on a physiologically relevant Q10
      value of 2.2, the lowest values of temperature-normalized rhizosphere respiration
      were observed from January to March, whereas the highest value was observed in
      early July when fine root growth is thought to be maximal.

PMID- 11303646
TI  - Fate of nitrogen released from 15N-labeled litter in European beech forests.
AB  - The decomposition and fate of 15N-labeled beech litter was monitored in three
      European beech (Fagus sylvatica L.) forests (Aubure, France; Ebrach, Germany; and
      Collelongo, Italy) for 3 years. Circular plots around single beech trees were
      isolated from roots of neighboring trees by soil trenching, and annual litterfall
      was replaced by 15N-labeled litter. Nitrogen was continuously released from the
      decomposing litter. However, over a 2-year period, this release was balanced by
      the incorporation of exogenous N. Released N accumulated mainly at the soil
      surface and in the topsoil. Microbial biomass remained almost constant during the
      experiment at all sites except for considerably lower values at Ebrach. The 15N
      enrichment of the microbial biomass increased strongly during the first year and
      then remained stable. The 15N released from the decomposing litter was rapidly
      detected in roots and leaves of the beech trees, increasing regularly and
      linearly over the course of the experiment. The uptake of litter-released 15N by
      the trees was reduced under conditions that reduced tree growth. Under these
      conditions, leaves and fine roots were the dominant N sinks, and little N was
      allocated to other plant parts. By contrast, N uptake and N allocation from
      leaves to stem and bark tissues increased when tree growth was enhanced. Budgets
      for 15N showed that 2 to 4% of litter-released N was incorporated into the trees,
      about 35% remained in the litter and about 50% reached the topsoil.

PMID- 11303647
TI  - Interactive effects of elevated CO2 concentration and nitrogen supply on
      partitioning of newly fixed 13C and 15N between shoot and roots of pedunculate
      oak seedlings (Quercus robur).
AB  - Pedunculate oak (Quercus robur L.) seedlings were grown for 3 or 4 months (second
      and third-flush stages) in greenhouses at two atmospheric CO2 concentrations
      ([CO2]) (350 or 700 micromol mol(-1)) and two nitrogen fertilization regimes (6.1
      or 0.61 mmol N l(-1) nutrient solution). Combined effects of [CO2] and nitrogen
      fertilization on partitioning of newly acquired carbon (C) and nitrogen (N) were
      assessed by dual 13C and 15N short-term labeling of seedlings at the second- or
      third-flush stage of development. In the low-N treatment, root growth, but not
      shoot growth, was stimulated by elevated [CO2], with the result that shoot/root
      biomass ratio declined. At the second-flush stage, overall seedling biomass
      growth was increased (13%) by elevated [CO2] regardless of N fertilization. At
      the third-flush stage, elevated [CO2] increased growth sharply (139%) in the high
      N but not the low-N treatment. Root/shoot biomass ratios were threefold higher in
      the low-N treatment relative to the high-N treatment. At the second-flush stage,
      leaf area was 45-51% greater in the high-N treatment than in the low-N treatment.
      At the-third flush stage, there was a positive interaction between the effects of
      N fertilization and [CO2] on leaf area, which was 93% greater in the high
      N/elevated [CO2] treatment than in the low-N/ambient [CO2] treatment. Specific
      leaf area was reduced (17-25%) by elevated [CO2], whereas C and N concentrations
      of seedlings increased significantly in response to either elevated [CO2] or high
      N fertilization. At the third-flush stage, acquisition of C and N per unit dry
      mass of leaf and fine root was 51 and 77% greater, respectively, in the elevated
      [CO2]/high-N fertilization treatment than in the ambient [CO2]/low-N
      fertilization treatment. However, there was dilution of leaf N in response to
      elevated [CO2]. Partitioning of newly acquired C and N between shoot and roots
      was altered by N fertilization but not [CO2]. More newly acquired C and N were
      partitioned to roots in the low-N treatment than in the high-N treatment.

PMID- 11303648
TI  - Seasonal changes in above- and belowground carbohydrate concentrations of
      ponderosa pine along a pollution gradient.
AB  - Seasonal patterns of carbohydrate concentration in coarse and fine roots, stem or
      bole, and foliage of ponderosa pine (Pinus ponderosa Laws) were described across
      five tree-age classes from seedlings to mature trees at an atmospherically clean
      site. Relative to all other tree-age classes, seedlings exhibited greater tissue
      carbohydrate concentration in stems and foliage, and greater shifts in the time
      at which maximum and minimum carbohydrate concentration occurred. To determine
      the effect of environmental stressors on tissue carbohydrate concentration, two
      tree-age classes (40-year-old and mature) were compared at three sites along a
      well-established, long-term O3 and N deposition gradient in the San Bernardino
      Mountains, California. Maximum carbohydrate concentration of 1-year-old needles
      declined with increasing pollution exposure in both tree-age classes. Maximum
      fine root monosaccharide concentration was depressed for both 40-year-old and
      mature trees at the most polluted site. Maximum coarse and fine root starch
      concentrations were significantly depressed at the most polluted site in mature
      trees. Maximum bole carbohydrate concentration of 40-year-old trees was greater
      for the two most polluted sites relative to the cleanest site: the bole appeared
      to be a storage organ at sites where high O3 and high N deposition decreased root
      biomass.

PMID- 11303649
TI  - Competition for water between walnut seedlings (Juglans regia) and rye grass
      (Lolium perenne) assessed by carbon isotope discrimination and delta18O
      enrichment.
AB  - Container-grown walnut seedlings (Juglans regia L.) were subjected to competition
      with rye grass (Lolium perenne L.) and to a 2-week soil drying cycle. One and 2
      weeks after the beginning of the drought treatment, H2 18O (delta approximately
      equals +100%) was added to the bottom layer of soil in the plant containers to
      create a vertical H2 18O gradient. Rye grass competition reduced aboveground and
      belowground biomass of the walnut seedlings by 60%, whereas drought had no
      effect. The presence of rye grass reduced the dry weight of walnut roots in the
      upper soil layer and caused a 50% reduction in lateral root length. Rye grass
      competition combined with the drought treatment reduced walnut leaf CO2
      assimilation rate (A) and leaf conductance (gw) by 20 and 39%, respectively.
      Transpiration rates in rye grass, both at the leaf level and at the plant or
      tiller level, were higher than in walnut seedlings. Leaf intrinsic water-use
      efficiency (A/gw) of walnut seedlings increased in response to drought and no
      differences were observed between the single-species and mixed-species
      treatments, as confirmed by leaf carbon isotope discrimination measurements.
      Measurement of delta18O in soil and in plant xylem sap indicated that the
      presence of rye grass did not affect the vertical profile of soil water uptake by
      walnut seedlings. Walnut seedlings and rye grass withdrew water from the top and
      middle soil layers in well-watered conditions, whereas during the drought
      treatment, walnut seedlings obtained water from all soil layers, but rye grass
      took up water from the bottom soil layer only.

PMID- 11303650
TI  - Fine root biomass and production in Scots pine stands in relation to stand age.
AB  - We determined fine root biomass and production of 15-, 35- and 100-year-old Scots
      pine (Pinus sylvestris L.) stands during three growing seasons. Fine roots were
      sampled by the soil core method. Mean (+/- SE) annual fine root biomass of Scots
      pine in the 15-, 35- and 100-year-old stands was 220 +/- 25, 357 +/- 21 and 259
      +/- 26 g m(-2), respectively. Fine root biomass of the understory vegetation was
      159 +/- 54 g m(-2), 244 +/- 30 and 408 +/- 81 g m(-2), and fine root necromass
      was 500 +/- 112, 1,047 +/- 452 and 1,895 +/- 607 g m(-2) in the sapling, pole
      stage and mature stands, respectively. Both understory and Scots pine fine root
      production increased with stand age. Mean annual Scots pine fine root production
      was 165 +/- 131, 775 +/- 339 and 860 +/- 348 g m(-2) year(-1) in the sapling,
      pole stage and mature stand, respectively. The respective mean annual production
      of all fine roots (Scots pine and understory) was 181 +/- 129, 1,039 +/- 497 and
      1,360 +/- 869 g m(-2) year(-1). The Scots pine and understory fine root biomass,
      necromass and production varied in relation to stand age, although the variation
      was not statistically significant.

PMID- 11303651
TI  - Rates and quantities of carbon flux to ectomycorrhizal mycelium following 14C
      pulse labeling of Pinus sylvestris seedlings: effects of litter patches and
      interaction with a wood-decomposer fungus.
AB  - We used a novel digital autoradiographic technique that enabled, for the first
      time, simultaneous visualization and quantification of spatial and temporal
      changes in carbon allocation patterns in ectomycorrhizal mycelia. Mycorrhizal
      plants of Pinus sylvestris L. were grown in microcosms containing non-sterile
      peat. The time course and spatial distribution of carbon allocation by P.
      sylvestris to mycelia of its mycorrhizal partners, Paxillus involutus (Batsch)
      Fr. and Suillus bovinus (L.): Kuntze, were quantified following 14C pulse
      labeling of the plants. Litter patches were used to investigate the effects of
      nutrient resource quality on carbon allocation. The wood-decomposer fungus
      Phanerochaete velutina (D.C.: Pers.) Parmasto was introduced to evaluate
      competitive and territorial interactions between its mycelial cords and the
      mycelial system of S. bovinus. Growth of ectomycorrhizal mycelium was stimulated
      in the litter patches. Nearly 60% of the C transferred from host plant to
      external mycorrhizal mycelium (> 2 mm from root surfaces) was allocated to
      mycelium in the patches, which comprised only 12% of the soil area available for
      mycelial colonization. Mycelia in the litter patch most recently colonized by
      mycorrhizal mycelium received the largest investment of carbon, amounting to 27
      to 50% of the total 14C in external mycorrhizal mycelium. The amount of C
      transfer to external mycelium of S. bovinus following pulse labeling was reduced
      from a maximum of 167 nmol in systems with no saprotroph to a maximum of 61 nmol
      in systems interacting with P. velutina. The 14C content of S. bovinus mycelium
      reached a maximum 24-36 h after labeling in control microcosms, but allocation
      did not reach a peak until 56 h after labeling, when S. bovinus interacted with
      mycelium of P. velutina. The mycelium of S. bovinus contained 9% of the total 14C
      in the plants (including mycorrhizae) at the end of the experiment, but this was
      reduced to 4% in the presence of P. velutina. The results demonstrate the dynamic
      manner in which mycorrhizal mycelia deploy C when foraging for nutrients. The
      inhibitory effect of the wood-decomposer fungus P. velutina on C allocation to
      external mycorrhizal mycelium has important implications for nutrient cycling in
      forest ecosystems.

PMID- 11303652
TI  - Influence of elevated CO2 and mycorrhizae on nitrogen acquisition: contrasting
      responses in Pinus taeda and Liquidambar styraciflua.
AB  - An understanding of root system capacity to acquire nitrogen (N) is critical in
      assessing the long-term growth impact of rising atmospheric CO2 concentration
      ([CO2]) on trees and forest ecosystems. We examined the effects of mycorrhizal
      inoculation and elevated [CO2] on root ammonium (NH4+) and nitrate (NO3-) uptake
      capacity in sweetgum (Liquidambar styraciflua L.) and loblolly pine (Pinus taeda
      L.). Mycorrhizal treatments included inoculation of seedlings with the arbuscular
      mycorrhizal (AM) fungus Glomus intraradices Schenck & Smith in sweetgum and the
      ectomycorrhizal (EM) fungus Laccaria bicolor (Maire) Orton in loblolly pine.
      These plants were then equally divided between ambient and elevated [CO2]
      treatments. After 6 months of treatment, root systems of both species exhibited a
      greater uptake capacity for NH4+ than for NO3-. In both species, mycorrhizal
      inoculation significantly increased uptake capacity for NO3-, but not for NH4+.
      In sweetgum, the mycorrhizal effect on NO3- and NH4+ uptake capacity depended on
      growth [C02]. Similarly, in loblolly pine, the mycorrhizal effect on NO3- uptake
      capacity depended on growth [CO2], but the effect on NH4+ uptake capacity did
      not. Mycorrhizal inoculation significantly enhanced root nitrate reductase
      activity (NRA) in both species, but elevated [CO2] increased root NRA only in
      sweetgum. Leaf NRA in sweetgum did not change significantly with mycorrhizal
      inoculation, but increased in response to [CO2]. Leaf NRA in loblolly pine was
      unaffected by either treatment. The results indicate that the mycorrhizal effect
      on specific root N uptake in these species depends on both the form of inorganic
      N and the mycorrhizal type. However, our data show that in addressing N status of
      plants under high [CO2], reliable prediction is possible only when information
      about other root system adjustments (e.g., biomass allocation to fine roots) is
      simultaneously considered.

PMID- 11303653
TI  - Carbon dioxide concentration and nitrogen input affect the C and N storage pools
      in Amanita muscaria-Picea abies mycorrhizae.
AB  - We studied the influence of elevated atmospheric CO2 concentration ([CO2]) on the
      vacuolar storage pool of nitrogen-containing compounds and on the glycogen pool
      in the hyphal sheath of Amanita muscaria (L. ex Fr.) Hooker-Picea abies L. Karst.
      mycorrhizae grown with two concentrations of ammonium in the substrate.
      Mycorrhizal seedlings were grown in petri dishes on agar containing 5.3 or 53 mg
      N l(-1) and exposed to 350 or 700 microl CO2 l(-1) for 5 or 7 weeks,
      respectively. Numbers and area of nitrogen-containing bodies in the vacuoles of
      the mycorrhizal fungus were determined by light microscopy linked to an image
      analysis system. The relative concentration of nitrogen in the vacuolar bodies
      was measured by electron energy loss spectroscopy (EELS). Glycogen stored in the
      cytosol was determined at the ultrastructural level by image analysis after
      staining the sections (PATAg test). Shoot dry weight, net photosynthesis and
      relative amounts of N in vacuolar bodies were greater at the higher N and CO2
      concentrations. The numbers and areas of vacuolar N-containing bodies were
      significantly greater at the higher N concentration only at ambient [CO2]. In the
      same treatment the percentage of hyphae containing glycogen declined to nearly
      zero. We conclude that, in the high N/low [CO2] treatment, the mycorrhizal fungus
      had an insufficient carbohydrate supply, partly because of increased amino acid
      synthesis by the non-mycorrhizal rootlets. When [CO2] was increased, the
      equilibrium between storage of glycogen and N-containing compounds was
      reestablished.

PMID- 11303654
TI  - Result of surgery for ruptured intracranial aneurysms in Nepal.
AB  - Although aneurysmal subarachnoid haemorrhage appears to be fairly common in the
      developing countries, the data on the results of management appear to be
      relatively sparse. This is a retrospective study of 40 patients with 44
      intracranial aneurysms operated upon at the National Neurosurgical Referral
      Centre in Kathmandu, Nepal from 1991 to 1999. The female male ratio was 1.5:1.
      Age ranged from 16 to 69 years with a mean of 43.2. In location, 18 (41%) were
      anterior communicating, 10 (23%) posterior communicating, nine (20%) middle
      cerebral, five (11%) internal carotid other than posterior communicating, two
      (5%) distal anterior cerebral and one (2%) posterior circulation. Multiple
      aneurysms were present in four (10%) and giant in three (8%). The timing of
      surgery ranged from 3 days to 3 months from the day of bleeding. Microsurgical
      clipping was possible in 37 (93%) and wrapping had to be done in three (7%).
      Overall mortality was four (10%), two (5%) had a surgery-related death and a
      further two (5%) died later due to pulmonary embolism. The remaining (90%) made a
      good recovery. The results compare favourably with that of the International
      Cooperative Study. Further reduction in mortality will have to await the
      introduction of endovascular techniques.

PMID- 11303655
TI  - Significance of CSF area measurements in cervical spondylitic myelopathy.
AB  - Mild clinical myelopathy can occur without cord compression, and asymptomatic
      cord compression seen on MRI is common. The aim of this study was to ascertain
      the MRI features which best correlate with early clinical myelopathy. The study
      was conducted on three groups: group A, 20 patients with clinical myelopathy and
      MRI evidence of cervical spondylosis; group B, 20 patients without myelopathy,
      but with other clinical and MRI evidence of cervical spondylosis; and group C, 10
      normal volunteers with no MRI evidence of spondylosis. The cross-sectional area
      (CSA) of the spinal cord (SP-CSA), spinal canal (SC-CSA) and CSF space (CSF-CSA)
      were measured on T1-weighted axial images at the level of the most severe spinal
      canal stenosis. The severity of myelopathy was assessed using a simple scoring
      system giving a score from 0 (normal) to 11 (severe). Subjective demonstration of
      cord compression on sagittal images was an insensitive indicator of clinical
      myelopathy. All three measures of cross-sectional area were significantly smaller
      in Group A than in B (p<0.01). The reduction in SP-CSA was the only independent
      prognosticator for severity of myelopathy (p<0.005) accounting for 63% of the
      variation in myelopathy score. All three variables showed a significant
      correlation with the presence of myelopathy (p<0.01); however, logistic
      regression analysis showed a decrease in CSF-CSA to be the only independent
      significant prognosticator of the presence of clinical myelopathy (p<0.02).
      Reduction of the CSF space to less than 0.7 cm2 was associated with a 90% chance
      of clinical myelopathy (specificity 83%).

PMID- 11303656
TI  - Acromegaly in the developing world--a 20-year teaching hospital experience.
AB  - A retrospective analysis was conducted to examine the long-term outcome of
      surgery, by a single pituitary surgeon and radiotherapy for acromegaly at Groote
      Schuur Hospital, Cape Town, using modern criteria for the definition of cure.
      Seventy-two patients (F/M ratio 1.3:1), aged 16-74 years, were eligible for
      inclusion. The mean follow-up period was 8.3 years. Macroadenomas were present in
      79%, microadenomas in 15% and tumour size was not documented in 6%. Pretreatment
      GH levels were, > or = 40 m U/l in 56 patients. Postoperatively, 21% of patients
      were cured, 40% controlled and 40% had hypopituitarism. After radiotherapy (mean
      follow-up 8.7 years) 43% were cured, 66% controlled and 78% had hypopituitarism.
      At follow-up 37% of patients traced had died. The most common cause of death was
      vascular disease. The poor surgical results may be attributed to late
      presentation in the developing world setting, as evidenced by tumour size and
      invasiveness, and the degree of GH elevation. Emphasis on early diagnosis of non
      invasive tumours is necessary to improve the cure rate and reduce mortality,

PMID- 11303657
TI  - Stereotactic radiosurgery XII. Large AVM and the failure of the radiation
      response modifier gamma linolenic acid to improve the therapeutic ratio.
AB  - Large arteriovenous malformations (AVM) are less likely to be 'cured' by single
      fraction stereotactically delivered radiation therapy (radiosurgery) and such
      treatment is attended by higher complication risks. Out of 200 successive AVM
      patients accepted for curative radiosurgery at St. Bartholomew's Hospital (and
      all treated by the same 6MV x-ray technique to 17.5 Gy marginal dose) were 62
      patients whose target volume exceeded 10 ml. Laboratory data demonstrating that
      gamma linolenic [omega-6-] acid (GLA) protected rat spinal cord from the damaging
      effect of single shot radiation prompted this study which employed GLA in
      conjunction with radiosurgery for large AVM. Without GLA, 41% of large AVM
      obliterated, but in the GLA treated cohort the obliteration rate was only 5.3% (p
      < 0.02). The permanent complication rates in the same patient groups were 20%
      versus 0%, respectively. There was a small skew to smaller volume 'large AVM' in
      the GLA treated cohort. This fact strengthens the conclusion concerning a
      difference for AVM obliteration, but could lead to a false conclusion quae GLA
      modulation of complications. When four patients were censored to minimize this
      possible bias, the risk for complications in the GLA treated patients was still
      significantly (p < 0.05), less than in the control group. We therefore conclude:
      (1) GLA spares AVM from radiation induced obliteration; (2) GLA modifies the
      response of normal human brain to radiation damage; (3) GLA does not improve the
      therapeutic ratio for AVM based radiosurgery; (4) GLA may have other uses
      (notably after radiation accidents and in radiation neuro-oncology, radiation
      cranial prophylaxis, chemoradiation protocols, whole brain radiation for
      metastases etc.).

PMID- 11303658
TI  - Endovascular management of acute subarachnoid haemorrhage in the elderly.
AB  - The objective of this study was to analyse the technical and clinical outcome in
      elderly patients receiving endovascular treatment for acutely ruptured
      intracranial aneurysms. The case notes and angiograms of 14 patients over the age
      of 69 years undergoing endovascular treatment for subarachnoid haemorrhage within
      the Interventional Neuroradiology Unit, Royal Perth Hospital over a period of 6
      years were retrospectively reviewed. The degree of angiographic occlusion
      achieved, and periprocedural, short-term and long-term clinical outcome were
      retrospectively assessed. Greater than 90% occlusion was obtained in 92% of
      cases. 82% of patients with Hunt and Hess grade I and II had an excellent
      clinical outcome. We conclude that endovascular coiling is an effective means of
      treating acute subarachnoid haemorrhage in grade I and II elderly patients.

PMID- 11303659
TI  - Endovascular treatment of posterior circulation aneurysms.
AB  - The objective of this paper was to analyse the technical and clinical outcome in
      patients receiving endovascular treatment for posterior circulation intracranial
      aneurysms at Royal Perth Hospital. The case notes and angiograms of 35 patients
      with ruptured and unruptured posterior circulation aneurysms treated by
      endovascular coil occlusion between 1992 and 1998 were included in the study. The
      degree of angiographic occlusion achieved, and periprocedural, short and long
      term clinical outcome were retrospectively analysed. Total aneurysm occlusion was
      achieved at initial treatment in 46% of cases, with 90% or greater occlusion
      achieved in 97% of cases. For aneurysms 12 mm or less in diameter, 100% of
      patients treated electively, and 100% of patients with grade I or II subarachnoid
      haemorrhage treated in the acute postictal phase had a good clinical outcome
      (Rankin Disability Score 1 and 2), with no serious morbidity or associated
      mortality. Excluding patients with grade V subarachnoid haemorrhage, the
      treatment-related serious morbidity rate was 3.4% and procedure-related mortality
      rate was 0%. We conclude that endovascular management provides an effective means
      of treatment for selected cases of posterior circulation aneurysms.

PMID- 11303660
TI  - Cerebral vasospasm following transsphenoidal removal of a pituitary adenoma.
AB  - We report a case of pituitary macroadenoma that developed symptomatic vasospasm
      12 days after transsphenoidal removal, but showed an excellent recovery following
      active treatment identical to those for vasopasm following aneurysmal
      subarachonid haemorrhage. Subarachnoid haematoma in the basal cisterns secondary
      from postoperative intracapsular haemorrhage was the most probable cause of the
      vasopasm.

PMID- 11303661
TI  - Cerebellar mutism caused by arteriovenous malformation of the vermis.
AB  - Transient mutism following posterior fossa tumour resection in children is well
      known in the literature. To our Knowledge, this phenomenon has never been
      reported without surgical intervention. We report a case of cerebellar mutism
      secondary haemorrhage from a vermian arteriovenous malformation (AVM), which
      resolved to ataxic dysarthria after 6 weeks. Embolization of the AVM was
      performed and the patient's clinical status continued to improve gradually till
      she became normal 6 months from the insult. The mutism was due to rupture of the
      AVM which might correlate the cerebellar mutism with the transient vasospasm of
      the blood vessels supplying the cerebellum. It is possible for a spontaneus
      posterior fossa bleed to result in transient mutism similar to post surgical
      mutism.

PMID- 11303662
TI  - Clinical and ethical standards in private practice.

PMID- 11303663
TI  - Aneurysmal bone cyst of the sphenoid sinus.
AB  - Aneurysmal bone cysts of the sphenoid sinus are very rare, with only six cases
      described in the literature. We present a case of an aneurysmal bone cyst of the
      sphenoid sinus with associated fibrous dysplasia in which the radiological
      findings had some features of a mucocoele. We discuss the differences in
      pathogenesis, clinical presentation and radiological appearances between these
      two lesions, and propose a simple drainage procedure as an effective modality of
      treatment.

PMID- 11303664
TI  - Arachnoid telangiectasia causing meningeal fibrosis and secondary syringomyelia.
AB  - A case of syringomyelia secondary to arachnoiditis associated with arachnoid
      telangiectasia is reported in a female patient with no other stigmata of
      hereditary haemorrhagic telangiectasia. Such a case has not been reported before.
      She underwent surgical decompression of the spinal cord with successful outcome.

PMID- 11303665
TI  - Management of brain stem abscess.
AB  - The brain stem is an uncommon site of a brain abscess. Such lesions were
      invariably fatal before 1974, when the arrival of computed tomography and
      magnetic resonance imaging improved the prognosis. This new case with a good
      result shows the usefulness of early diagnosis, careful clinical and radiological
      monitoring and combined medical and surgical management. A child 2 1/2 years of
      age was admitted to the department of neurosurgery for diagnosis and treatment of
      a brain stem lesion. The clinical context and discovery of an intrabronchial
      foreign body, as well as neuroradiological investigations, suggested a diagnosis
      of brain stem abscess. Initial treatment with broad spectrum antibiotics with
      good cerebral penetration was associated with an increase in the size of the
      abscess and clinical worsening. Stereotactic aspiration of lesion was performed
      by a transpeduncular approach under CT guidance and general anaesthesia.
      Secondary thoracotomy enabled removal of an intrabronchial needle. After
      evacuation, in spite of failure to identify the organism, neurological deficit
      resolved rapidly and the lesion no longer appeared on CT. Management of a brain
      abscess always includes antibiotics. They must cover the organisms most often
      encountered in brain abscesses and have good cerebral penetration. Medical
      treatment seems to suffice for small abscesses. A brain stem abscess with rapid
      clinical signs, together with current neuroradiogical diagnostic techniques,
      enables early discovery of such abscesses when they are still small. Treatment of
      brain stem abscesses includes primary antibiotic therapy, then stereotaxic
      drainage when there is any diagnostic doubt, poor clinical tolerability or
      antibiotic resistance.

PMID- 11303666
TI  - Primary diffuse leptomeningeal gliomatosis.
AB  - Primary diffuse leptomeningeal gliomatosis is a rare central nervous system
      neoplasm in which focal or diffuse evidence of gliomatous tissue is identified in
      the subarachnoid space with no evidence of a primary tumour. A case is presented
      and the differential diagnosis and management are discussed.

PMID- 11303667
TI  - Synovial cyst: a rare late complication of lumbar arthrodesis?
AB  - The authors describe a rare late complication of lumbar arthrodesis, a synovial
      cyst occurring in association with overuse of the underlying facet joint.

PMID- 11303668
TI  - Pontine glioma and cerebellopontine angle epidermoid tumour occurring as
      collision tumours.
AB  - A 36-year-old male was admitted with a 10-year history of gradually progressive
      left ear hearing loss, diplopia and right hemiparesis. Magnetic resonance imaging
      showed a left lateral pontine enhancing tumour and an additional cerebellopontine
      angle epidermoid tumour in close proximity forming a collision tumour. On
      exploration, the epidermoid tumour and the intraaxial pontine glioma were
      completely resected. The literature on collision tumours is reviewed.

PMID- 11303669
TI  - Cauda equina xanthogranulomatosis.

PMID- 11303671
TI  - Microvascular decompression for trigeminal neuralgia in patients over 65 years of
      age.

PMID- 11303670
TI  - Echinococcus infestation of the splenius capitis.

PMID- 11303672
TI  - CSF rhinorrhoea: the place of endoscopic sinus surgery.
AB  - Cerebrospinal fluid (CSF) rhinorrhoea has been managed by both neurosurgeons and
      otorhinolaryngologists, with neurosurgeons often choosing an intracranial
      approach and otorhinolaryngologists an extracranial approach. Recently,
      transnasal endoscopic techniques have been introduced that significantly reduce
      the morbidity of surgical repair when compared with previous techniques. The
      sense of smell was preserved in all patients who underwent an endoscopic repair
      of their CSF leak where it was present preoperatively. The results of transnasal
      endoscopic repair now make it the treatment of choice for most anterior cranial
      and sphenoid CSF leaks, with the exception of defects in posterior wall of the
      frontal sinus or defects larger than 5 cm. It is vital that a diagnosis of a CSF
      leak is confirmed by immunofixation of beta 2 transferrin as unilateral
      rhinorrhoea can masquerade as a CSF leak. We illustrate our experience with 78
      patients who were referred with a diagnosis of CSF rhinorrhoea.

PMID- 11303673
TI  - All change at the GDC?

PMID- 11303674
TI  - Can mandibles be grown?

PMID- 11303676
TI  - Regular versus occasional attendees.

PMID- 11303675
TI  - Graduate debt.

PMID- 11303677
TI  - Temazepam dangers.

PMID- 11303678
TI  - Microbial aerosols.

PMID- 11303679
TI  - Gender challenge.

PMID- 11303680
TI  - Gender challenge.

PMID- 11303681
TI  - Endocarditis cases.

PMID- 11303682
TI  - Smoking cessation.

PMID- 11303683
TI  - Dental attitudes and behaviours in 1998 and implications for the future.
AB  - The 1998 Adult Dental Health Survey included face to face interviews with
      participants to determine their dental attitudes and behaviours. This article
      considers reported oral hygiene practices, treatment choices, satisfaction with
      appearance of teeth, attitudes towards wearing dentures and how these have
      changed since previous surveys. Although overall there has been a steady
      improvement in dental health attitudes, adults from disadvantaged households are
      still lagging behind. This has implications for social equity.

PMID- 11303684
TI  - Initial prosthetic treatment.
AB  - This article describes measures designed to provide short-term solutions to
      existing RPD problems and to establish an optimum oral environment for the
      provision of definitive prostheses.

PMID- 11303685
TI  - The laser welding technique applied to the non precious dental alloys procedure
      and results.
AB  - AIM: The laser welding technique was chosen for its versatility in the repair of
      dental metal prosthesis. The aim of this research is to assess the accuracy,
      quality and reproducibility of this technique as applied to Ni-Cr-Mo and Cr-Co-Mo
      alloys often used to make prosthesis METHOD: The alloy's ability to weld was
      evaluated with a pulsed Nd-Yag Laser equipment. In order to evaluate the joining,
      various cast wires with different diameters were used. The efficiency of the
      joining was measured with tensile tests. In order to understand this difference,
      metallographic examinations and X-Ray microprobe analysis were performed through
      the welded area and compared with the cast part. RESULTS: It was found that a
      very slight change in the chemistry of the Ni-Cr alloys had a strong influence on
      the quality of the joining. The Co-Cr alloy presented an excellent weldability. A
      very important change in the microstructure due to the effect of the laser was
      pointed out in the welding zone, increasing its micro-hardness. CONCLUSION: The
      higher level of carbon and boron in one of the two Ni-Cr was found to be
      responsible for its poor welding ability. However for the others, the maximum
      depth of welding was found to be around 2mm which is one of the usual thicknesses
      of the components which have to be repaired.

PMID- 11303686
TI  - Dental erosion in a group of British 14-year-old school children. Part II:
      Influence of dietary intake.
AB  - OBJECTIVES: The aims of the present study were first to investigate the dietary
      intake pattern of UK teenagers and secondly to determine the relationship, if
      any, between dental erosion and dietary intake in these children. METHODS: The
      study group consisted of a cluster random sample of 14-year-old school children
      in Birmingham, UK: 418 children were examined from 12 different schools; 209 were
      male and 209 female. Data on the rate and frequency of consumption of drinks,
      foods, and fruits were obtained from a self-reported questionnaire supplemented
      by a structured interview. The data were analysed using SPSS with Chi-square, and
      Spearman correlation analysis. RESULTS: Over 80% of the teenagers regularly
      consumed soft drinks but approximately half of these children had a relatively
      low weekly consumption. However, 13% and 10% respectively had more than 22
      intakes per week of cola and other carbonated drinks. Almost a quarter of these
      14-year-olds had alcoholic drinks, with significantly more males than females
      involved (Chi-square P < 0.05) . Girls had a greater intake of fruits.
      Statistically significant correlations were found between the prevalence of
      erosion and the consumption of soft drinks, carbonated beverages, alcohol drinks,
      fresh fruits, Vitamin-C tablets and foodstuffs (Spearman correlation analysis P <
      0.05). CONCLUSION: It was concluded that consumption particularly of soft drinks
      was high and common in teenage school children in Birmingham, UK. In addition
      there was a relationship between dental erosion and acidic dietary intake.
      Further investigation of the erosive potential of these drinks and foods is
      required.

PMID- 11303687
TI  - Can dental attendance improve quality of life?
AB  - OBJECTIVE: The aim of this study was to determine the relationship between
      reported dental attendance patterns and the public's perception of how oral
      health impacts on quality of life (QoL). METHOD: A national UK study involving a
      random probability sample of 2,668 adults. Respondents were interviewed in their
      homes about how oral health affects their QoL and about their dental attendance
      pattern. Responses were coded as oral health having a negative impact, positive
      impact or impact in general (either positive and/or negative) on QoL. RESULTS:
      The response rate was 70% with 1,865 adults participating in the study. 72%
      (1,340) reported that their oral health affected their QoL in general, 57%
      (1,065) reported that it had a positive effect, and 48% (902) that it had a
      negative effect. 61% (1,136) reported to have attended the dentist within the
      last year- 'regular attenders'. Bivaraite analysis identified association between
      perception of how oral health impacts on QoL and dental attendance pattern (P <
      0.01). When socio-demographic factors (age, gender, and social class) were taken
      into account in the analysis, 'regular attenders' reported that oral health had
      greater impact in general on QoL (OR = 1.30, 95% CI = 1.04, 1.63) and,
      specifically, a greater positive impact (OR = 1.49, 95% CI=1.44, 1.77).
      CONCLUSION: Dental attendance is associated with perceptions of how oral health
      impacts on QoL, specifically enhanced life quality. This may have implications
      for understanding the health gain of regular dental attendance.

PMID- 11303688
TI  - A profile of the dentists working in the community dental service in the United
      Kingdom in 1999.
AB  - AIM: To profile the staff in the community dental service (CDS) in terms of
      qualifications, clinical service provisions and gender. METHOD: Postal
      questionnaire to all clinical dental service managers in the United Kingdom.
      RESULTS: The response rate was in the order of 99%. A higher proportion (67.5%)
      of community dental staff are women, but they are more likely (P < 0.001) to work
      part time. There were a higher proportion of men (14.1%) in the most senior
      management grade when compared with women (6.1%). A postgraduate qualification is
      relatively common, but men are more likely (P < 0.001) to have a higher
      qualification. The CDS provides a wide range of services centering on clinical
      care for adults and children, special needs care, epidemiology and health
      promotion. Most managers tended to have a clinical role. CONCLUSIONS: Women play
      an important part in the CDS. They are more likely to work part time, tend to
      occupy lower positions in the organisation and are less likely to have a
      postgraduate qualification than men.

PMID- 11303689
TI  - Trust me, I'm a dentist.

PMID- 11303690
TI  - I go to a friend.

PMID- 11303691
TI  - Selective coronary angiography: 42 years later.

PMID- 11303692
TI  - The cardiovascular response to sexual activity: do we know enough?
AB  - Interest in comprehensive cardiac rehabilitation over the past 25 years spawned a
      series of small investigations concerning the heart rate, blood pressure, and
      ischemic response to sexual intercourse. This information was adequate for
      advising patients about return to sexual activity after a myocardial infarction
      or cardiac surgery. However, the introduction of medications for erectile
      dysfunction enabled impotent cardiac patients to engage in sexual activity and
      has highlighted the need for more detailed information concerning cardiovascular
      physiology during coitus. Review of the medical literature indicates a remarkable
      paucity of such data despite dramatic advances in most other aspects of
      cardiovascular physiology and pathophysiology. This brief paper gives an overview
      of the current knowledge of the cardiovascular response to sexual activity and,
      within the framework of advances in cardiology, highlights areas where it appears
      important to fill in the knowledge gap.

PMID- 11303693
TI  - Lessons learned from statin trials.
AB  - This article aims to review lessons learned about lipid lowering and statins in
      the past decade and to consider what developments the future may hold. Results
      from a series of landmark clinical trials confirm that statins significantly
      reduce cardiovascular morbidity and mortality in patients with and without
      previous coronary artery disease. The potential of this drug class has yet to be
      fully explored. Studies currently under way will answer many of the outstanding
      questions.

PMID- 11303694
TI  - Methylenetetrahydrofolate reductase gene polymorphism and risk of premature
      myocardial infarction.
AB  - BACKGROUND: Elevated plasma homocysteine level is an independent risk factor for
      cardiovascular disease. A common mutation (nucleotid 677C-T) in the gene coding
      for methylenetetrahydrofolate reductase (MTHFR) has been reported to reduce the
      enzymatic activity of MTHFR and is associated with elevated plasma levels of
      homocysteine, especially in subjects with low folate intake. HYPOTHESIS:
      Methylenetetrahydrofolate reductase T/T genotype may be a risk factor for
      premature MI in Turkish population who are known to have low folate levels.
      METHODS: The study group was comprised of 96 men (aged <45 years) with premature
      myocardial infarction (MI) and 100 age- and gender-matched controls who had no
      history or clinical evidence of coronary artery disease (CAD) and/or MI. DNA was
      extracted from peripheral blood and genotypes were determined by polymerase chain
      reaction, restriction mapping with HinfI, and gel electrophoresis. Conventional
      risk factors for CAD were prospectively documented. RESULTS: Allele and genotype
      frequencies among cases and control subjects were compatible with Hardy-Weinberg
      equilibrium. The frequencies of T/T, C/T, and C/C genotypes among patients with
      MI and control subjects were 15.6, 40.6, and 43.8%, and 5, 35, and 60%,
      respectively. Multivariate analyses identified smoking, MTHFR C/T polymorphism,
      diabetes mellitus, family history of CAD, and hypertension as the independent
      predictors of premature MI. Defining patients with non-T/T genotype (C/C and C/T
      combined) as reference, the relative risk of MI for subjects with T/T genotype
      was 5.94 (95% confidence interval: 1.96-18.02, p = 0.0016). CONCLUSIONS: Our
      findings suggest that C677T transition in the MTHFR gene may be a risk factor for
      premature MI in Turkish men.

PMID- 11303695
TI  - Endothelial dysfunction and decreased exercise tolerance in interferon-alpha
      therapy in chronic hepatitis C: relation between exercise hyperemia and
      endothelial function.
AB  - BACKGROUND: We previously reported that reversible endothelial dysfunction is
      caused by interferon-alpha therapy (IFN) in patients with chronic hepatitis C. In
      experimental studies, limb blood flow during exercise is reported to be dependent
      on endothelium-derived nitric oxide. HYPOTHESIS: The purpose of this study was to
      confirm the effect of IFN on endothelial function and to investigate whether
      exercise hyperemia is dependent on endothelial function in humans. METHODS: We
      performed symptom-limited exercise treadmill testing and measured flow-mediated
      vasodilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl
      trinitrate-induced dilation (GTN-D, 0.3 mg, endothelium-independent vasodilation)
      in the brachial artery by using high-resolution ultrasound in 10 patients with
      chronic active hepatitis C (age 53 +/- 11 years, 2 men, 8 women) before and
      immediately after administration of recombinant interferon 2b (10 million U/day)
      for 4 weeks. RESULTS: There were no significant abnormal findings in any patients
      in routine studies of 24-h ambulatory electrocardiogram monitoring, two
      dimensional echocardiography, and exercise treadmill testing both before and
      after treatment. Leg fatigue and exhaustion were the reasons for termination of
      exercise treadmill testing in each patient. Pressure rate product was calculated
      at rest and peak exercise. Interferon-alpha therapy significantly (p<0.05)
      decreased FMD (6.8 +/- 3.1 vs. 1.9 +/- 2.6%), exercise treadmill testing
      tolerance time (437 +/- 89 vs. 395 +/- 62 s) and peak pressure rate product (283
      +/- 41 vs. 241 +/- 47 mmHg x beats/min x 10(-2)), but not GTN-D (13.4 +/- 5.4 vs.
      17.0 +/- 5.5%). The change of FMD due to IFN significantly and highly correlated
      with exercise treadmill testing tolerance time (r = 0.86, p<0.001), but not with
      change of peak pressure rate product, suggesting that FMD is more closely related
      to the condition of the peripheral circulation than is cardiac performance.
      CONCLUSION: These results suggest that IFN in patients with chronic hepatitis C
      impairs endothelial function and exercise tolerance, and that endothelial
      function might be at least partly involved in exercise hyperemia in humans.

PMID- 11303696
TI  - A new noninvasive method for evaluation of coronary endothelial function in
      hypertensive patients based on change in diameter of the left main coronary
      artery induced by cold pressor test using echocardiography.
AB  - BACKGROUND: Coronary endothelial function is frequently studied by measuring the
      vasodilator response of coronary arteries to acetylcholine or to cold pressor
      test by invasive quantitative coronary angiography. Because invasive methods have
      substantial inherent limitations, studies should attempt to evaluate coronary
      endothelial function noninvasively. HYPOTHESIS: We attempted to evaluate the
      accuracy of measurement of the percent change in diameter of the left main trunk
      induced by cold pressor test with two-dimensional (2-D) echocardiography.
      Furthermore, we applied this method to the evaluation of coronary artery
      endothelial function in hypertensive patients. METHODS: We measured the left main
      trunk diameter in 21 subjects (51 +/- 4 years) before and after cold pressor test
      using quantitative coronary angiography followed immediately by 2-D
      echocardiography. The accuracy of measurement of the left main trunk diameter and
      its percent change by echocardiography was evaluated by comparing the values
      obtained by the two methods. In addition, using echocardiography, we compared
      left main trunk diameter responses to cold pressor test in 16 hypertensive
      patients [51 +/- 5 years (mean +/- standard deviation)] and 16 matched healthy
      subjects (50 +/- 4 years). RESULTS: Although there was only a weak correlation
      between the absolute values of the left main trunk diameter measured by the two
      methods (r = 0.61; p = 0.04), a strong correlation was found between the percent
      change in diameter measured by the two methods (r = 0.93; p = 0.0001). The
      percent change in diameter of the left main trunk induced by cold pressor test in
      hypertensive patients (-3.7 +/- 10.6%) was significantly lower than that in
      control subjects (13.2 +/- 6.8%, p = 0.0001). CONCLUSIONS: Percent change in
      diameter of the left main trunk induced by cold pressor test can be evaluated
      accurately using 2-D echocardiography. Our study showed reduced vasodilation or
      vasoconstriction of the left main trunk after cold pressor test in hypertensive
      patients compared with healthy subjects, indicating impaired coronary endothelial
      function in hypertensive patients. The present echocardiographic method is a
      potentially useful new noninvasive method for evaluating coronary endothelial
      function.

PMID- 11303697
TI  - Frequency of atrial septal aneurysm in patients with recent stroke: preliminary
      results from a multicenter study.
AB  - BACKGROUND: The role of atrial septal aneurysm (ASA) as a risk factor for
      cerebral ischemia of unknown etiology is controversial. Recent studies have found
      an association between ASA and focal ischemic events, while results from other
      studies suggest a low incidence of embolism in patients with ASA. HYPOTHESIS: The
      present study was designed to evaluate the frequency of ASA, a minor
      cardioembolic source, in patients with a recent stroke presenting with normal
      carotid arteries. METHODS: In all, 394 patients with cerebral ischemic stroke
      were referred to our institutions. Patients underwent transthracic and
      transesophageal echocardiography and carotid artery ultrasound examination. The
      study population included 215 patients without significant arterial disease.
      Frequency and morphologic characteristics of ASA were evaluated. RESULTS:
      Transthoracic examination showed ASA in 39 patients (18%), while transesophageal
      echocardiography showed ASA in 61 patients (28%). A patent foramen ovale was
      found in 47 patients (21.8%) and was associated with ASA in 40 patients (65.5%).
      We observed an increased thickness of the aneurysmatic wall (3.80 +/- 1.7 mm) in
      all patients with ASA. CONCLUSIONS: The present study confirms the relationship
      between ASA and stroke in patients with normal carotid arteries. The most common
      abnormality associated with ASA was patent foramen ovale. We suggest that
      patients who have a stroke in the absence of significant carotid disease undergo
      transesophageal echocardiography to identify possible underlying septal
      abnormalities.

PMID- 11303698
TI  - Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum
      level in patients with chest pain and normal coronary arteries (syndrome X).
AB  - BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1)
      and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to
      vascular endothelium may implicate in the pathogenesis of the syndrome of chest
      pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether
      markers of endothelial activation are raised in patients with chest pain and
      normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in
      36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary
      artery disease (CAD), and a positive response to exercise test; in 21 patients (6
      men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary
      arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women,
      aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher
      both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p <
      0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29).
      VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients
      with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS:
      ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with
      syndrome X compared with control individuals. These findings may suggest the
      presence of chronic inflammation with involvement of the endothelium in patients
      with anginal chest pain and normal coronary angiograms.

PMID- 11303699
TI  - Possible causes of symptoms in suspected coronary heart disease but normal
      angiograms.
AB  - BACKGROUND: In patients with suspected coronary heart disease and normal
      angiography, the causes of cardiac symptoms frequently remain undetermined. A
      correct diagnosis is desirable, however, since some of the underlying disorders
      may be curable, treatable, influence prognosis, or induce screening of the
      relatives. HYPOTHESIS: In such patients, the prevalence of arterial hypertension,
      hemochromatosis, hypothyroidism, hypoparathyroidism, tachycardiomyopathy,
      amyloidosis, and neuromuscular disorders as a possible cause for their symptoms
      and the seroprevalence of micro-organisms, known to cause myocardial damage, were
      assessed. METHODS: Consecutive patients with normal coronary angiograms were
      invited for two visits comprising clinical history and investigation,
      electrocardiograms, blood tests, and echocardiography. Patients were investigated
      neurologically if unexplained anginal chest pain or creatine kinase elevation
      persisted or if echocardiography showed isolated left ventricular abnormal
      trabeculations. RESULTS: In 71 patients (31 women, 40 men, mean age 60 years),
      the most common cause for cardiac symptoms was hypertension (66%), followed by
      neuromuscular disorders (13%), tachycardiomyopathy (9%), hypothyroidism (4%), and
      hemochromatosis (3%). The seroprevalence for Chlamydia species was 90%,
      Helicobacter pylori 70%, Chlamydia pneumoniae 63%, Borrelia burgdorferi sensu
      lato 15%, and Rickettsia conorii 10%. No possible cause was found in 24% of the
      patients. CONCLUSIONS: In patients with suspected coronary heart disease and
      normal angiograms, hypertension, neuromuscular disorders, tachycardiomyopathy,
      hypothyroidism, and hemochromatosis should be considered as possible causes.

PMID- 11303700
TI  - Relationships between heart rate variability, functional capacity, and left
      ventricular function following myocardial infarction: an evaluation after one
      week and six months.
AB  - BACKGROUND: Relationships between heart rate (HR) variability and different
      prognostic markers such as ejection fraction, functional capacity, and patency of
      the infarct-related artery, as well as the comparison of their time courses are
      not fully elucidated. HYPOTHESIS: The aim of study was to assess prospectively
      the early postinfarction changes in HR variability and its evolution over a
      period of 6 months: the relationships between HR variability and functional
      capacity in exercise testing; left ventricular function in cardiac
      catheterization: status of the infarct-related artery; and the comparison of
      their time courses. METHODS: In 42 patients with anterior myocardial infarction,
      a study was made of the early changes in HR variability analyzed by the complex
      demodulation method, its evolution over a period of 6 months. and the
      relationships between HR variability and (1) functional capacity in exercise
      testing, (2) left ventricular function in cardiac catheterization, and (3) status
      of the infarct-related artery. RESULTS: At 1 week HR variability parameters
      correlated directly with functional capacity indicators such as METS, percent
      change in HR from rest to peak exercise (%deltaHR), difference between initial
      and peak HR (HR range), percent peak theoretical HR (% peak HR), left ventricular
      ejection fraction (EF), and, inversely, with end-systolic volume (ESV). Stepwise
      multiple regression analysis to establish HR variability parameters (recorded at
      1 week) as related to functional capacity and left ventricular function at 1 week
      and 6 months postinfarction established the following variables: (1) At 1 week:
      standard deviation (SD) of the RR cycles in relation to %deltaHR (r = 0.60, p
      <0.0001), HR range (r = 0.43, p < 0.01), and EF (r = 0.79, p < 0.0001). (2) At 6
      months, the sole accepted HR variability parameter was the SD in relation to
      %deltaHR (r = 0.38, p < 0.05) and HR range (r = 0.45, p < 0.01). No variability
      parameter was accepted in relation to METS, % peak HR, or ESV. Relationship
      between EF or ESV and HR variability parameters was not significant when both
      were evaluated at 6 months. At that time, there was a significant increase in all
      HR variability parameters among all surviving patients (n = 39), with the
      exception of the LF/HF ratio and mean RR cycle. The percent increase in HR
      variability between the first week and 6 months was greater among those patients
      with the lowest basal EF. No relation was established between HR variability and
      patency of the infarct-related artery. CONCLUSION: The decrease in HR variability
      observed following myocardial infarction is associated with a diminished
      functional capacity and an increased alteration of the EF. This does not affect
      the recovery of HR variability, which was observed in all surviving patients.

PMID- 11303701
TI  - Transmyocardial laser revascularization: is the enthusiasm justified?
AB  - BACKGROUND: Transmyocardial laser revascularization (TMLR) is advocated to offer
      relief of incapacitating angina for patients whose coronary vessels are poor
      targets for coronary artery bypass graft surgery (CABG) or balloon angioplasty
      and stenting. In spite of significant mortality and morbidity, the preliminary
      reports from centers performing the procedure were quite enthusiastic for a
      period of about 1 year following the procedure. HYPOTHESIS: The study aimed to
      determine mortality, morbidity, and long-term results of TMLR. METHODS: The study
      included 19 individuals with incapacitating angina not suitable for CABG or
      percutaneous balloon angioplasty. Patients were followed up clinically for death,
      myocardial infarction, heart failure, arrhythmia, and repeated hospital
      admissions for unstable angina or other conditions. Stress testing with
      radionuclide tracers was done following surgery in patients who were not
      unstable. RESULTS: Of 19 patients, 8 experienced significant morbidity. There was
      one hospital death. Four died within 17 months. Relief from angina of two classes
      or more was present in 15 of 18 patients (83.3%) for a variable time period. Mean
      time for anginal relief was 8.0 months (range 1-30 months). At last follow-up,
      only two patients with a hybrid procedure (both CABG and TMLR in the same
      sitting) had mild angina for 17 and 29 months, respectively. All others with a
      mean follow-up period of 21.2 months (range 6-53 months) developed unstable
      angina or had a large area of ischemia on stress radionuclide studies. Despite a
      high incidence of significant angina in patients after TMLR, hospitalization was
      reduced from an average of 42.6 days pre procedure in the year before to 21 days
      during the follow-up period post procedure. CONCLUSION: Transmyocardial laser
      revascularization is associated with significant relief of angina pectoris in the
      majority of patients with severe diffuse coronary artery disease; however, this
      relief is short-lived in most. When mortality and morbidity are factored in, TMLR
      cannot be enthusiastically recommended.

PMID- 11303702
TI  - Collagen remodeling and cardiac dysfunction in patients with hypertrophic
      cardiomyopathy: the significance of type III and VI collagens.
AB  - BACKGROUND: The relationship between the extent of myocardial interstitial
      fibrosis, the percentage of each type of collagen, and cardiac function in
      patients with hypertrophic cardiomyopathy (HC) has not been established.
      HYPOTHESIS: The study aimed to establish that increases in some types of collagen
      may correlate with cardiac dysfunction. METHODS: Mallory-Azan staining and
      immunohistochemical staining by the avidin-biotin-complex (ABC) method using
      anticollagen antibodies were performed on the myocardial biopsy specimens in 35
      patients with HC, and the percentage and type of collagen present was determined.
      Left ventricular (LV) function was evaluated by cardiac catheterization and
      ventriculography. RESULTS: The percentage of myocardial interstitial fibrosis
      correlated highly with indices of LV diastolic and systolic function. The amount
      of type III collagen correlated significantly with the peak negative dp/dt, the
      rapid filling volume/stroke volume, and the ejection fraction (EF). Significant
      correlations also were noted between the amount of type VI collagen and peak
      negative dp/dt, peak positive dp/dt, and EF. Type I collagen did not correlate
      with any of the LV function indices, and type IV collagen correlated only with
      peak ejection rate. Type V collagen did not accumulate substantially in the
      myocardial interstitium. CONCLUSIONS: The progression of myocardial interstitial
      fibrosis in the HC heart adversely impacts both the diastolic and systolic
      function of the LV. Increases in the percentage of type III and VI collagen
      correlate with cardiac dysfunction.

PMID- 11303703
TI  - Clusters of life-threatening ventricular arrhythmias in patients with implanted
      cardioverter-defibrillators: prevalence, characteristics, and risk
      stratification.
AB  - BACKGROUND: Series of discharges from an implanted defibrillator (ICD) to
      terminate life-threatening ventricular tachyarrhythmias are one particular aspect
      of energy use and success of ICD therapy. Little is known about prevalence.
      characteristics, and risk stratification of so-called "cluster arrhythmias."
      HYPOTHESIS: The objective of this study was to examine the frequency of cluster
      arrhythmias, to characterize the temporal relationship precisely, and to assess
      the accompanying circumstances of their occurrence, whereby risk stratification
      was to be made if appropriate. METHODS: In all, 63 consecutive patients were
      followed prospectively over 727 +/- 684 days to determine the presence and
      characteristics of cluster arrhythmias (45,801 patient days). In 30 patients, 374
      ICD episodes of ventricular tachyarrhythmias were analyzed for their temporal
      relationship. After a first successfully terminated ventricular tachyarrhythmia,
      further ICD discharges within 3 h were observed during 145 of 374 (39%) episodes;
      mean time interval between these arrhythmias was 25 +/- 32 min. RESULTS:
      Arrhythmia clusters occurred in 19 of 30 (63%) patients. In multivariate
      analysis, only underlying heart disease was predictive for accumulation of
      ventricular tachyarrhythmias. Cluster arrhythmias were more frequent among
      patients with ischemic heart disease than among those with nonischemic heart
      disease (40.0 vs. 29.2%, p < 0.05). Ejection fraction, age, gender, and other
      parameters were not predictive for occurrence of arrhythmia clusters. In 4 of 19
      patients, accumulation of ICD discharges was predictive for new onset of
      myocardial ischemia elicited by exercise test. CONCLUSIONS: Cluster arrhythmias
      are most common in patients with ICDs with coronary heart disease and may
      indicate disease progression and increasing instability, for example, due to new
      onset of myocardial ischemia.

PMID- 11303704
TI  - Long-term angiographic follow-up after successful repeat balloon angioplasty for
      in-stent restenosis.
AB  - BACKGROUND: Coronary stent implantation is associated with improved angiographic
      short-term and mid-term clinical outcome. However, restenosis rate still remains
      between 20 and 30%. HYPOTHESIS: The purpose of the study, performed as a
      prospective angiographic follow-up to detect restenosis, was to evaluate the
      immediate and the 6-month angiographic results of repeat balloon angioplasty for
      in-stent restenosis. METHODS: From April 1996 to September 1997, 335 stenting
      procedures performed in 327 patients underwent prospectively 6-month control
      angiography. Of the 96 lesions that showed in-stent restenosis (> 50% diameter
      stenosis) (29%), 72 underwent balloon angioplasty. RESULTS: The primary success
      rate was 100%. Follow-up angiogram at a mean of 6.9 +/- 2.4 months was obtained
      in 54 patients. Recurrent restenosis was observed in 24 of the 55 stents (44%).
      Repeat intervention for diffuse and body location in-stent restenosis before
      repeat intervention was associated with significantly higher rates of recurrent
      restenosis (p < 0.001 and p < 0.05, respectively). Of the 19 patients who
      underwent further balloon angioplasty (100% success rate), coronary angiography
      was performed in 18 (95%) at a mean of 8.2 +/- 2.0 months and showed recurrent
      restenosis in 12 patients (67%). Further repeat intervention for diffuse and
      severe in-stent restenosis before the second repeat intervention was associated
      with significantly higher rates of further recurrent restenosis (p < 0.05 and p <
      0.005, respectively). CONCLUSIONS: Although balloon angioplasty can be safely,
      successfully, and repeatedly performed after stent restenosis, it carries a
      progressively high recurrence of angiographic restenosis rate during repeat 6
      month follow-ups. The subgroup of patients with diffuse, severe, and/or body
      location in-stent restenosis proved to be at higher risk of recurrent restenosis.

PMID- 11303705
TI  - Random fasting hyperglycemia as cardiovascular risk factor in the elderly: a 6
      year longitudinal study.
AB  - A large body of evidence suggests that diabetes increases the risk of coronary
      heart disease (CHD), but whether fasting hyperglycemia is associated with a major
      risk for CHD is still under debate. The aim of the present study was to
      investigate the role played by fasting hyperglycemia in the development of
      cardiovascular disease (CVD) in an elderly population when associated with common
      risk factors for CVD (i.e., hypertension, hypercholesterolemia, smoking, etc). We
      analyzed a sample of 455 subjects aged > or = 60 years. The risk factors taken
      into account were systolic and diastolic blood pressure levels, use of
      antihypertensive drugs, total serum cholesterol, serum triglycerides, and smoking
      habit. Glycemia was measured at entry on a fasting sample. During the follow-up
      period (mean 6 years), the occurrence of CVD was monitored (criteria for the
      occurrence of CVD included total cardiovascular mortality, fatal or nonfatal
      myocardial infarction, symptomatic coronary heart disease [stable and unstable
      angina], the need for percutaneous transluminal coronary angioplasty or coronary
      artery bypass graft, fatal or nonfatal stroke, and transient ischemic attack). A
      total of 427 subjects completed the follow-up. During this period, 73 subjects
      (17.10%) developed CVD according to the above criteria. A Cox proportional hazard
      model was designed to evaluate the contribution of variables in predicting CVD.
      Relative risks and 95% confidence intervals for CVD were calculated from the
      regression coefficients to study the association between the risk of developing
      CVD and predicting variables. We found a relation between occurrence of CVD and
      fasting hyperglycemia: subjects with fasting glycemia, > 126 mg/dl at enrollment,
      but without previous clinical diagnosis of diabetes, showed a 2.01 times higher
      risk than those with fasting glycemia < 126 mg/dl. Hence, random fasting
      hyperglycemia can predict the occurrence of CVD in elderly subjects.

PMID- 11303706
TI  - Images in cardiology. Giant left ventricular pseudoaneurysm.

PMID- 11303707
TI  - Embolic stroke and cardiac papillary fibroelastoma.
AB  - Papillary fibroelastomas are rare, benign, primary cardiac tumors. They are,
      however, the most common primary tumor of the cardiac valves and may cause great
      morbidity risk from embolization. This paper reports the case of a healthy 34
      year-old man who presented with symptoms of a right occipital embolic stroke.
      Transesophageal echocardiography revealed a papillary fibroelastoma on the
      anterior leaflet of the mitral valve. The papillary fibroelastoma was surgically
      excised and he has had no recurrent symptoms. This case illustrates the
      importance of obtaining a transesophageal echocardiogram to investigate a
      possible embolic source in patients with ischemic stroke.

PMID- 11303708
TI  - Charles Richard Conti.

PMID- 11303709
TI  - Effects of lifetime volleyball exercise on bone mineral densities in lumbar
      spine, calcaneus and tibia for pre-, peri- and postmenopausal women.
AB  - To clarify the effects of habitual volleyball exercise on bone in women during
      the menopausal periods, we measured bone mineral densities (BMDs) of the lumbar
      spine, calcaneus and tibia every 12 months for 2 years and estimated factors
      related to the baseline values and annual loss rates. Forty Japanese female
      volleyball players 42-62 years of age, who had belonged to the district non
      professional club for more than 10 years on average, were recruited. Twenty women
      had regular menstruation at the start, but 7 underwent menopause during the
      study. Fifty-nine healthy women who did not participate in habitual exercise, but
      were otherwise comparable with the players, were recruited as the controls. The
      lumbar and calcaneus BMDs were measured by dual-energy X-ray absorptiometry
      (DXA), and both the volumetric BMDs and cross-sectional geometry at the diaphysis
      of the tibia were measured by peripheral quantitative computed tomography. The
      baseline BMDs of all measured sites and the values of the cortical area and
      moment of inertia of the tibia in the players were significantly higher than the
      values in the control women. In the peri- and postmenopausal players, the
      baseline values of the lumbar and calcaneus BMDs related to total years of
      participating in regular exercises during adulthood including volleyball (TYE),
      body mass index (BMI) and years since menopause (YSM). Tibia cortical area and
      moment of inertia values related to TYE. Annual bone loss rates in the tibia and
      calcaneus of players were significantly smaller than those values in the
      controls. However, the bone loss rates in the lumbar spine did not differ
      significantly between the groups. The bone loss rate in the calcaneus was
      significantly related to the current number of training hours per week and YSM.
      The rate of bone loss in the tibia was related to BMI. These data indicated that
      the total number of years participating in exercise activity during adulthood
      have positive effects on lumbar and calcaneus BMDs and the cortical structure of
      the tibia. Habitual volleyball exercise apparently did not alleviate the
      menopause-related bone loss in the lumbar spine.

PMID- 11303710
TI  - Intravenous pamidronate as treatment for osteoporosis after heart
      transplantation: a prospective study.
AB  - Fractures due to osteoporosis are one of the major complications after heart
      transplantation, occurring mostly during the first 6 months after the graft, with
      an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral
      density (BMD) decreases dramatically following the graft, at trabecular sites as
      well as cortical sites. This is explained by the relatively high doses of
      glucocorticoids used during the months following the graft, and by a long-term
      increase of bone turnover which is probably due to cyclosporine. There is some
      evidence for a beneficial effect on BMD of antiresorptive treatments after heart
      transplantation. The aim of this study was to assess prospectively the effect on
      BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate,
      combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart
      transplant recipients, and that of a treatment with calcium and vitamin D in
      heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the
      femoral neck was measured by dual-energy X-ray absorptiometry in all patients
      every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16
      men) aged 46+/-4 years (mean +/- SEM) received only calcium and vitamin D. A
      significant decrease in BMD was observed after 6 months following the graft, at
      the lumbar spine (- 6.6%) as well as at the femoral neck (-7.8%). After 2 years,
      BMD tended to recover at the lumbar spine, whereas the loss persisted after 3
      years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46+/-4 years
      (mean +/- SEM) started treatment with pamidronate on average 6 months after the
      graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD
      T-score below -2.5 SD). Over the whole treatment period, a continuous increase in
      BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared
      with the BMD at the time of the graft). BMD at the femoral neck was lowered in
      the first year by -3.4%, but recovered totally after 3 years of treatment. In
      conclusion, a 3-year study of treatment with pamidronate given every 3 months to
      patients with existing osteoporosis led to a significant increase in lumbar spine
      BMD and prevented loss at the femoral neck. However, since some of these patients
      were treated up to 14 months after the transplant, they may already have passed
      through the phase of most rapid bone loss. In patients who were not osteoporotic
      at baseline, treatment with calcium and vitamin D alone was not able to prevent
      the rapid bone loss that occurs immediately after transplantation.

PMID- 11303711
TI  - Quantitative ultrasound of bone and markers of bone turnover in Cushing's
      syndrome.
AB  - Quantitative ultrasound (QUS) of bone is a valuable tool in the assessment of
      postmenopausal osteoporosis. QUS and new markers of bone turnover have been
      poorly assessed in Cushing's syndrome, however. Twenty-five patients with
      Cushing's syndrome (20 women, 3 men; mean age +/- SEM: 38+/-2 years) were studied
      and compared with 35 age- and sex-matched control patients (mean age +/- SEM:
      38+/-2 years). The following variables were measured in both groups: QUS
      parameters at the heel (BUA; SOS; Stiffness Index, SI); bone mineral density
      (BMD) at both the lumbar spine (LS) and femoral neck (FN) by dual-energy X-ray
      absorptiometry; and serum markers of bone turnover (osteocalcin, procollagen type
      I N- and C-terminal propeptides (PINP and PICP), bone alkaline phosphatase (BAP),
      procollagen type I C-terminal telopeptide (ICTP) and urinary type I collagen C
      telopepetide breakdown products (CTX)). Both BUA and SI were decreased in
      patients with Cushing's syndrome (p<0.01) but not SOS (p=0.08). BMD was also
      strongly decreased in Cushing's syndrome, at both the LS and FN (p<0.005). The
      two markers of bone turnover statistically significantly different between the
      two groups were osteocalcin (mean + SEM: 3.5 + 0.7 ng/ml (Cushing's syndrome) vs
      6.4+/-0.5 ng/ml (controls, p<0.01)) and CTX (mean +/- SEM: 148.7+/-17.1
      microg/mmol Cr (Cushing's syndrome) vs 220.8+/-22.9 microg/mmol Cr (controls),
      p<0.05). The areas under the receiver operating characteristic curve (AUC) were
      0.72 (BUA), 0.73 (SI), 0.90 (BMD(LS)), 0.81 (BMD(FN)), 0.83 (osteocalcin) and
      0.64 (CTX) respectively. AUC was significantly higher for BMD(LS) than for both
      BUA and SI (p<0.05). Conversely AUC was not statistically significantly different
      for BMDFN as compared with either BUA or SI. AUC was also higher for osteocalcin
      than for other markers of bone turnover. In conclusion, QUS of bone seems to be a
      relevant tool for assessing bone involvement in Cushing's syndrome. QUS does have
      a lower sensitivity compared with DXA, however, and the relevance of QUS cannot
      be ascertained until some longitudinal data are forthcoming. Except for CTX, the
      other new markers of bone turnover assessed in this study (PINP, PICP, BAP and
      ICTP) do not seem of interest in Cushing's syndrome.

PMID- 11303712
TI  - A population-based study of fracture incidence in southern Tasmania: lifetime
      fracture risk and evidence for geographic variations within the same country.
AB  - Symptomatic fractures are a significant problem in terms of both morbidity and
      financial cost. Marked variation in both total and site-specific fracture
      incidence has been documented internationally but there is limited within-country
      data. This prospective population-based study documented the incidence of all
      symptomatic fractures occurring from July 1, 1997 to June 30, 1999 in adults > or
      =50 years of age resident in Southern Tasmania (total population > or = 50 years:
      64688). Fractures were ascertained by reviewing reports from all the radiology
      providers within the area. There were 701 fractures in men and 1309 fractures in
      women. The corresponding fracture incidence in men and women was 1248 and 1916
      per 100000 person-years, respectively. Residual lifetime fracture risk in a
      person aged 50 years was 27% for men and 44% for women with fractures other than
      hip fractures constituting the majority of symptomatic fracture events. These
      fracture risk estimates remained remarkably constant with increasing age. In
      comparison to Geelong, there were significantly lower hip fracture rates (males:
      RR 0.59, 95% CI 0.45-0.76; females: RR 0.61, 95% CI 0.53-0.71) but significantly
      higher distal forearm fractures (males: RR 1.87, 95% CI 1.10-3.78; females: RR
      1.31, 95% CI 1.11-1.55) and total fractures in men (RR 1.31, 95% CI 1.17-1.46)
      but not women (RR 1.05, 95% CI 0.98-1.13). In contrast, Southern Tasmania had
      lower age-standardized rates of all fractures compared with Dubbo (RR 0.28-0.79).
      In conclusion, this study provides compelling evidence that fracture incidence
      varies between different geographic sites within the same country, which has
      important implications for health planning. In addition, the combination of high
      residual fracture risk and short life expectancy in elderly subjects suggests
      fracture prevention will be most cost-effective in later life.

PMID- 11303713
TI  - Intensive and prolonged health promotion strategy may increase awareness of
      osteoporosis among postmenopausal women.
AB  - The aim of the study was to measure the results of a 15-year health promotion
      strategy towards osteoporosis, in an urban community of subjects over 45 years
      old, in terms of osteoporosis awareness and handling. To this end an ancillary
      study to a large survey of the Belgian population's self-perceived health status
      was carried out. A rectangular sample of 4800 individuals over 45 years old was
      randomly selected in two Belgian cities, among the affiliates of the two main
      health insurance providers. One of the cities (Liege) had been, since the early
      1980s, the target of a constant health promotion strategy, directed to both the
      medical community and the general population, aimed at increasing osteoporosis
      awareness in women after the menopause. During the same period, no particular
      steps were taken in the other city (Aalst) to increase osteoporosis awareness in
      the community. In our study, the participants were asked to spontaneously report
      any chronic, serious and/or severe disorders that they had been suffering from,
      for at least 6 months, during the previous 12 months. They also provided a list
      of drugs they were taking at the time of the survey. Osteoporosis was reported to
      be a disease affecting 1.5% of men in Aalst and 1.3% of men in Liege (p = 0.61).
      For women, osteoporosis was reported to be present in 4.8% in Aalst and 10.8% in
      Liege (p<0.001). Self-reporting of osteoporosis prevalence in Liege was
      statistically significantly higher in women aged 45-64 years, 65-74 years or over
      75 years (p<0.001). Obesity, alcohol consumption or physical activity were
      equally distributed between women from Liege and Aalst. Prescription drugs used
      for osteoporosis had been delivered to a similar proportion of men in Aalst and
      Liege. In women, a statistically significant difference in these prescription
      drugs was observed between Liege and Aalst, both for the overall population
      (p<0.001) and in each of the age classes (p<0.001 for 45-64 years and 65-74
      years; p<0.009 for over 75 years). A continuous long-term health promotion
      strategy, directed toward both physicians and the general population, thus
      appears to increase awareness about osteoporosis in women over 45 years and/or in
      the medical community. This is reflected by an increase in self-reported
      prevalence of osteoporosis and in the prescription of drugs aimed at prevention
      and treatment of this disorder. Whether these observations reflect an appropriate
      diagnosis and a proper handling of the disease remains to be evaluated by
      objective diagnostic tools such as bone densitometry and by an evaluation of the
      effectiveness of prescription practices in postmenopausal women.

PMID- 11303714
TI  - Hip fracture incidence in east and west germany: reassessement ten years after
      unification.
AB  - The rising incidence of hip fractures is of world wide concern. In addition to
      the demographically aging populations world wide a secular trend of hip fracture
      incidence has been reported for various populations. The objective of the current
      study was to reassess hip fracture incidence ten years following German
      reunification and compare incidence rates in former East and West Germany. Data
      from the German hospital discharge diagnosis registry were used to compare rates
      in former East and West Germany. A reassessment of a secular trend was done with
      directly age-standardized rates of the population 60 years old and over.
      Significant differences were found between incidence rates in the East and West
      German states with higher rates in the West. Compared to earlier studies for East
      Germany, rate in East Germany have increased by on average annually 6% since
      reunification. This is a steep increase compared to the annual rise by about 3%
      between 1974 and 1989. Hip fracture incidence in East Germany thereby has doubled
      during the 25-year period from 1971 to 1996. Although the observed acceleration
      of a secular trend in East Germany probably has multiple causes, evidence
      suggests a significant influence of Western life style on hip fracture incidence.

PMID- 11303715
TI  - A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.
AB  - The aim of the study was to review the effect of etidronate on bone density and
      fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998,
      examined citations of relevant articles, and the proceedings of international
      osteoporosis meetings. We contacted osteoporosis investigators to identify
      additional studies, primary authors, and pharmaceutical industry sources for
      unpublished data. We included 13 trials that randomized women to etidronate or an
      alternative (placebo or calcium and/or vitamin D) and measured bone density for
      at least 1 year. For each trial, three independent reviewers assessed the
      methodologic quality and abstracted data. The data suggested a reduction in
      vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92).
      There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69
      to 1.42). Etidronate, relative to control, increased bone density after 1-3 years
      of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral
      neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39
      to 1.55). Effects were larger at 4 years, though the number of patients followed
      much smaller. Etidronate increases bone density in the lumbar spine and femoral
      neck for up to 4 years. The pooled estimates of fracture reduction with
      etidronate suggest a reduction in vertebral fractures, but no effect on
      nonvertebral fractures.

PMID- 11303716
TI  - Bone mineral density of 704 amateur sportsmen involved in different physical
      activities.
AB  - The aim of the study was to analyze the relation between sports and bone mass.
      Seven hundred and four men with no history of chronic disease were questioned on
      their adolescent and adult sporting activities. Their total body (TB) and
      regional (head, spine, arms and legs) bone mineral density (BMD) were measured by
      dual-energy X-ray absorptiometry. BMD measurements and ratios of regional BMD to
      TB BMD were compared using a multiple regression analysis. Probands (mean age 30
      years) were engaged in 14 sports activities: rugby, soccer, other team sports,
      endurance running, fighting sports, bodybuilding, multiple weightbearing
      activities, swimming, swimming with flippers, biking, rowing, climbing, triathlon
      and multiple mixed activities. They stated that they were practising a physical
      activity at the amateur level: 7.1 h/week between the ages of 11 and 18 years and
      9 h/week between age 18 years and the day of the interview (no significant
      difference between physical activities). Rowers and swimmers had low TB BMD (1.22
      and 1.17 g/cm2) and low leg BMD (1.37 and 1.31 g/cm2). Participants in rugby,
      soccer, other team sports and fighting sports had a high TB BMD (1.27-1.35 g/cm2)
      and high leg BMD (1.41-1.5 g/cm2). For head BMD, there was no stastistical
      difference among the different groups. Constructed ratios pointed out the site
      specific adaptation of the skeleton: soccer player and runners had a higher leg
      ratio; bodybuilders, fighters, climbers and swimmers had a higher arm ratio;
      rugby players had a higher spine ratio. Head ratio was higher in non
      weightbearing sports (rowing, swimming) than in weightbearing sports (rugby, team
      sports, soccer, fighting sports and bodybuilding). Thus the BMD and ratio
      differences among the 14 disciplines seem to be site-specific and related to the
      supposedly high and unusual strains created at certain sites during sport
      training by muscle stress and gravitational forces. Head ratio is closely related
      to the type of practice; its value could predict whether sport participants have
      developed the maximal peak bone mass they could achieve.

PMID- 11303717
TI  - Vertebral morphometry: a comparison of long-term precision of morphometric X-ray
      absorptiometry and morphometric radiography in normal and osteoporotic subjects.
AB  - Vertebral morphometry, the quantification of vertebral body shape, has proved a
      useful tool in the identification and evaluation of osteoporotic vertebral
      deformities in both epidemiologic surveys and clinical trials. Although
      conventionally it has been performed on lateral radiographs of the thoracolumbar
      spine (morphometric radiography, MRX), it may now be accomplished on morphometric
      X-ray absorptiometry (MXA) scans, acquired on dual-energy X-ray absorptiometry
      (DXA) machines. In this study the long-term precision of vertebral height
      measurement using MXA and MRX was directly compared. Initially 24 postmenopausal
      women were recruited (mean age 67+/-5.8 years): 12 normal subjects (group 1) and
      12 with osteoporosis and known vertebral deformities (group 2). Each subject
      attended for a baseline visit at which they had a MXA examination and lateral
      thoracic and lumbar radiographs. Twenty-one subjects then returned 1.7+/-0.4
      years later (10 subjects from group 1 and 11 from group 2) for a follow-up visit
      to repeat both the MXA scans and conventional radiographs. The baseline MXA scans
      and conventional radiographs were each analyzed quantitatively by two observers
      in a masked fashion, using a standard six-point method. The follow-up images were
      then analyzed by the same observers. The MRX observers were masked to the
      baseline analyses, while the MXA observers utilized the manufacturer's 'compare'
      facility. On all scans and radiographs anterior (Ha), mid (Hm) and posterior (Hp)
      vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios
      calculated for each vertebral body, ideally from T4 to L4. MRX analyzed 129 of
      the 130 available vertebrae in group 1 at both visits and 141 of the 143
      available in group 2, while MXA analyzed 124 vertebrae in group 1 at both visits
      and 127 in group 2. Intra- and inter-observer precision errors, particularly in
      terms of coefficient of variation (CV%), were larger for MXA than for MRX in both
      normal subjects and those with vertebral deformities. For example, intra-observer
      precision errors for vertebral height measurement were 0.62 mm (2.9%) for MXA
      compared with 0.63 mm (2.2%) for MRX in group 1 (normal) subjects and 0.82 mm
      (4.2%) for MXA compared with 0.85 mm (3.3%) for MRX for group 2 (osteoporosis and
      vertebral deformities) subjects. Both MXA and MRX inter-observer precision was
      clearly poorer than the intra-observer precision, a problem associated with any
      morphometric technique. This was particularly noticeable for MXA; for example,
      precision of vertebral height measurement in group 1 subjects was 0.62 mm (2.9%)
      for intra-observer compared with 0.99 mm (4.6%) for inter-observer analyses. MXA
      and MRX intra- and inter-observer precision was significantly poorer for subjects
      with vertebral deformities compared with those without, with the CV% for subjects
      with vertebral deformity approximately 50% greater than that of normal subjects.
      For example, MRX intra-observer precision for the midwedge ratio was 2.6% for
      group 1 subjects compared with 3.8% for group 2 subjects. The precision of
      vertebral height measurement on deformed vertebrae of group 2 subjects was poorer
      than that for normal vertebrae in the same subjects using both MXA and MRX, as a
      result of increased variability in point placement. For example, MXA intra
      observer precision (RMS SD) for the wedge ratio precision was 0.037 (3.9%) for
      normal vertebrae compared with 0.060 (6.6%) for deformed vertebrae. We conclude
      that MXA precision was generally poorer than MRX, although both techniques were
      adversely affected by the presence of vertebral deformities and the use of more
      than one observer. Although precision errors for both techniques were
      substantially smaller than the 20-25% reduction in vertebral height frequently
      proposed to identify incident deformities, the poorer precision of MXA may lead
      to an increased risk of erroneous classification of vertebrae as normal or
      deformed.

PMID- 11303718
TI  - Designation T-score and Z-score reported on the bone density tests.

PMID- 11303720
TI  - Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping:
      a prospective, population-based study in men and women.
AB  - Osteoporosis is a common disease with a strong genetic component, characterized
      by reduced bone mineral density and increased fracture risk. Although the genetic
      basis of osteoporosis is incompletely understood, previous studies have
      identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that
      predicts bone mineral density and osteoporotic fractures in several populations.
      Here we investigated the role of COLIA1 genotyping and bone densitometry in the
      prediction of osteoporotic fractures in a prospective, population-based study of
      men (n = 156) and women (n = 185) who were followed up for a mean (+/- SEM) of
      4.88+/-0.03 years. There was no significant difference in bone density, rate of
      bone loss, body weight, height, or years since menopause between the genotype
      groups but women with the 'ss' genotype were significantly older than the other
      genotype groups (p = 0.03). Thirty-nine individuals sustained 54 fractures during
      follow-up and these predominantly occurred in women (45 fractures in 30
      individuals). Fractures were significantly more common in females who carried the
      COLIA1 's' allele (p = 0.001), although there was no significant association
      between COLIA1 genotype and the occurrence of fractures in men. Logistic
      regression analysis showed that carriage of the COLIA1 's' allele was an
      independent predictor of fracture in women with an odds ratio (OR) [95% CI] of
      2.59 [1.23-5.45], along with spine bone mineral density (OR = 1.57 [1.04-2.37]
      per Z-score unit) and body weight (OR = 1.05 [1.01-1.10] per kilogram). Moreover,
      bone densitometry and COLIA1 genotyping interacted significantly to enhance
      fracture prediction in women (p = 0.01), such that the incidence of fractures was
      45 times higher in those with low BMD who carried the 's' allele (24.3
      fractures/100 patient-years) compared with those with high BMD who were 'SS'
      homozygotes (0.54 fracture/100 patient-years). We conclude that in our
      population, COLIA1 genotyping predicts fractures independently of bone mass and
      interacts with bone densitometry to help identify women who are at high and low
      risk of sustaining osteoporotic fractures.

PMID- 11303719
TI  - Prevalent vertebral deformity predicts incident hip though not distal forearm
      fracture: results from the European Prospective Osteoporosis Study.
AB  - The presence of a vertebral deformity increases the risk of subsequent spinal
      deformities. The aim of this analysis was to determine whether the presence of
      vertebral deformity predicts incident hip and other limb fractures. Six thousand
      three hundred and forty-four men and 6788 women aged 50 years and over were
      recruited from population registers in 31 European centers and followed
      prospectively for a median of 3 years. All subjects had radiographs performed at
      baseline and the presence of vertebral deformity was assessed using established
      morphometric methods. Incident limb fractures which occurred during the follow-
      up period were ascertained by annual postal questionnaire and confirmed by
      radiographs, review of medical records and personal interview. During a total of
      40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture.
      Amongst the women, after adjustment for age, prevalent vertebral deformity was a
      strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1
      9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4),
      though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive
      risk increased with increasing number of prevalent deformities, particularly for
      subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3).
      Amongst men, vertebral deformity was not associated with an increased risk of
      incident limb fracture though there was a nonsignificant trend toward an
      increased risk of hip fracture with increasing number of deformities. In summary,
      prevalent radiographic vertebral deformities in women are a strong predictor of
      hip fracture, and to a lesser extent humerus and 'other' limb fractures; however,
      they do not predict distal forearm fractures.

PMID- 11303721
TI  - Risk factors for ankle fracture.
AB  - Ankle fractures are frequently observed in postmenopausal women although the
      pattern of incidence and risk factor profile suggest that ankle fracture may not
      be a typical osteoporotic fracture. The aims of this study were to determine the
      prevalence of osteopenia and vertebral fracture and to evaluate the diagnostic
      accuracy of dual-energy X-ray absorptiometry (DXA), anthropometry, lifestyle and
      reproductive factors in women who have sustained an ankle fracture. We studied
      103 women aged 50-80 years (mean 63.2, 7.9 SD) with ankle fracture. These were
      compared with 375 women aged 50-86 years (mean 64.5, 9.1 SD) from a population
      based cohort. Bone mineral density (BMD) at the lumbar spine (LS) and
      contralateral proximal femur (including femoral neck (FN), Ward's triangle (WT)
      and trochanteric region (TR)) was measured by DXA. Quantitative ultrasound (QUS)
      of the calcaneus and proximal digits was measured using three different devices.
      Radiographs of the thoracolumbar spine were taken (anteroposterior and lateral
      views). There were no significant differences in the prevalence of osteoporosis
      (T<-2.5 level) at the LS, FN and WT sites. The population-based cohort had lower
      TR BMD than the ankle fracture cohort. Age-and weight-adjusted Z-scores of FN BMD
      were significantly lower in the ankle fracture group. Age- and weight-adjusted Z
      scores of QUS gave contradictory results. There were no differences in the
      receiver operating characteristics of DXA compared with QUS. Twenty-seven women
      (7%) of the population-based cohort and 10 women (10%) of the ankle fracture
      cohort were found to have prevalent vertebral fractures; these were not
      significantly different.

PMID- 11303722
TI  - HMG-1 rediscovered as a cytokine.
AB  - High-mobility group-1 (HMG-1), an abundant, highly conserved cellular protein, is
      widely known as a nuclear DNA-binding protein that stabilizes nucleosome
      formation, facilitates gene transcription, and regulates the activity of steroid
      hormone receptors. We discovered that HMG-1 is a late mediator of delayed
      endotoxin lethality. When released by activated monocytes, it participates in the
      development of lethality and it activates downstream cytokine release. This
      review covers the general features of HMG-1 and its newly appreciated role as a
      cytokine.

PMID- 11303723
TI  - The effect of trauma on neutrophil L-selectin expression and sL-selectin serum
      levels.
AB  - Among identified adhesion molecules, the L-selectin on neutrophils enables the
      first step of leukocyte adherence to activated endothelial cells. To allow firm
      adhesion of neutrophils, L-selectin is then split off the cell membrane. It was
      hypothetized that an increase of the constitutively high serum level of soluble L
      selectin may indicate an ongoing pathological neutrophil sequestration to the
      endothelial cells associated with activation and injury of the cells. To evaluate
      this hypothesis, sL-selectin serum levels and neutrophil L-selectin expression of
      healthy volunteers (group A, n = 15), as well as of surgical patients, were
      investigated. Group B (n = 26) included patients subjected to elective limb
      surgery (mean operation time, 122 min), and group C (n = 45) comprised trauma
      patients. sL-selectin serum levels were measured daily over a 14-day period.
      Neutrophil L-selectin expression was evaluated by FACS analysis using the
      humanized anti-L-selectin antibody HuDreg 55 over a period of 3 days at minimum
      in both experimental groups. The binding of sL-selectin to endothelial cells was
      also examined in vitro. Elective limb surgery resulted in lower pre- and post
      operative sL-selectin plasma levels (800-1,000 ng/mL) compared to healthy
      volunteers (1,100-1,200 ng/mL) with insignificant changes throughout the study
      period. Trauma patients revealed even lower sL-selectin levels (400-600 ng/mL).
      When these patients were discriminated by the multiple organ dysfunction (MOD)
      score of Moore in +MOD (n = 9, ISS = 31.7) and -MOD (n = 36, ISS = 25.0), a
      significant difference became evident. In +MOD patients sL-selectin levels
      remained on a low basis of 350 ng/mL, whereas in -MOD patients the initial low sL
      selectin level subsequently rose to 800 ng/mL, similar to that of elective
      surgery patients. FACS analysis revealed a significant drop in neutrophil L
      selectin expression 24 h after trauma compared to normal. Also, +MOD and -MOD
      patients were significantly discriminated by the L-selectin expression at this
      time. The in vitro studies revealed evidence for binding of sL-selectin to
      endothelial cells independently on the presence of neutrophils. According to our
      data, increasing severity of the post-operative/posttraumatic course is
      associated with decreasing sL-selectin serum levels and also reduced neutrophil L
      selectin expression. In view of the in vitro results, this probably indicates
      competitive enhanced binding of sL-selectin to endothelial cells, thus masking
      the elevated activation of neutrophils and their ability for endothelial
      adherence.

PMID- 11303724
TI  - Coagulopathy following major liver resection: the effect of rBPI21 and the role
      of decreased synthesis of regulating proteins by the liver.
AB  - This prospective study investigated the role of reduced hepatic synthesis of
      regulating proteins in coagulopathy after partial hepatectomy (PH) compared with
      major abdominal surgery (MAS) without involvement of the liver. Furthermore, we
      studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy
      after PH was studied. Compared with MAS, PH resulted in significantly elevated
      levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes.
      Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2
      macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment
      with rBPI21 led to significantly lower levels of tissue-type plasminogen
      activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was
      associated with significantly higher bilirubin and t-PA plasma levels and
      significantly lower levels of alpha2-M. This study indicates that PH induced
      hepatic failure results in decreased synthesis of hepatic regulating plasma
      proteins and subsequent activation of coagulation and fibrinolysis. Prevention of
      t-PA release by rBPI21 may have important clinical implications. Decreased
      availability of alpha2-M may be a factor in post-operative DIC.

PMID- 11303725
TI  - Feasibility of biolistic gene therapy in burns.
AB  - Skin is an especially attractive target for genetic manipulation because it is
      readily accessible and easily monitored for both the presence and the expression
      of inserted genes. This study was designed to assess the feasibility of particle
      mediated gene transfer to burned skin and to compare the transfection efficiency,
      anatomic distribution, and duration of transgene expression achievable in normal
      versus burned skin. Two days following scald injury of varying depths in 60
      degrees C water (10 s: superficial partial; 20 s: deep partial; 40 s: full
      thickness) reporter gene (beta-galactosidase) constructs were delivered using a
      gene gun at various helium pressures (200-600 psi) to normal and burned skin. A
      time course study was performed to examine the kinetics of transgene expression.
      Animals received a superficial partial thickness burn and were sacrificed 12 h,
      1, 3, 5, 7, 14, or 21 days after gene transfer. India Ink injection and
      immunohistochemistry were used to assess the depth of the scald injury.
      Transfection efficiency was measured in skin homogenates 24 h after gene transfer
      by morphometric and chemoluminescent assays. We found that the extent of tissue
      damage was directly related to the duration of heat source exposure. Reporter
      gene activity was significantly higher in superficial partial thickness burns
      compared to normal controls and gradually declined with increasing tissue injury.
      No activity was seen in the full thickness burn group. Beta-galactosidase
      activity reached a maximum level 12 h after gene transfer in both normal and
      superficial partial thickness burned skin with no levels seen after 5 days post
      transfection. These findings indicate that particle-mediated gene transfer in
      thermally injured skin is feasible and may provide a means of introducing
      biologic agents into injured tissue capable of enhancing bacterial clearance and
      improving wound healing.

PMID- 11303726
TI  - Differential local and systemic regulation of the murine chemokines KC and MIP2.
AB  - We characterized the relative biological activity and expression of two murine
      chemokines that may serve as functional homologues for human IL-8, KC, and
      macrophage inflammatory protein 2 (MIP2). Recombinant chemokines were produced in
      bacterial expression systems and antibodies specific for KC or MIP2 were raised.
      In vitro assays showed that KC elicited 4-fold greater neutrophil chemotaxis
      compared with MIP2, while MIP2 elicited significantly greater release of
      elastase. Lipopolysaccharide- (LPS) stimulated macrophages (8 h) secreted more
      MIP2 (approximately 10 ng/mL) compared with KC (approximately 4 ng/ml) and
      expression of either murine chemokine was independent of TNFalpha or IL-1beta
      production. Thioglycollate (thio) and glycogen (gly) induced peritonitis produced
      more KC (thio = 7.1 and gly = 2.5 ng/mL) in the peritoneum compared with MIP2
      (thio = 4.5 and gly = 0.3 ng/mL). Plasma KC levels were very high after either
      challenge (approximately 24 ng/mL), which was >50-fold more than the systemic
      increase in MIP2 (approximately 0.3 ng/mL). Our data demonstrate that while KC
      and MIP2 have similar in vitro production characteristics, KC appears to be a
      more potent and systemically distributed chemokine during acute in vivo
      inflammation, while MIP2 expression appears limited to localized expression.

PMID- 11303727
TI  - Evaluation of the safety of recombinant P-selectin glycoprotein ligand
      immunoglobulin G fusion protein in experimental models of localized and systemic
      infection.
AB  - P-selectin is a major component in the early interaction between platelets,
      endothelial cells, and inflammatory cells in the initial phases of the innate
      immune response. The major ligand for P-selectin is P-selectin glycoprotein
      ligand-1 (PSGL-1) and this ligand is expressed on the surface of monocyte,
      lymphocyte, and neutrophil membranes. A truncated form of recombinant human P
      selectin glycoprotein ligand-1 has been covalently linked to immunoglobulin G
      (rPSGL-Ig) and this fusion peptide functions as a competitive inhibitor of PSGL
      1. As an inhibitor of neutrophil-endothelial cell adherence, rPSGL-Ig is in early
      clinical development for the treatment of ischemia reperfusion injury. To
      determine the potential for deleterious effects from inhibition in P-selectin
      mediated neutrophil attachment in the presence of bacterial infection, the
      effects of therapeutic doses of rPSGL-Ig were tested in three standard laboratory
      sepsis models. The experimental models included: the murine systemic Listeria
      monocytogenes infection model, the Pseudomonas aeruginosa bacteremia model in
      neutropenic rats, and the cecal ligation and puncture (CLP)-induced peritonitis
      model in rats. Recombinant human PSGL-Ig had no adverse effects on mortality or
      immune clearance in systemic bacterial infection in any of the three infection
      models. The PSGL-1 inhibitor did significantly decrease local neutrophil
      infiltration and bacterial clearance in the peritoneum following CLP, but this
      did not increase the systemic levels of proinflammatory cytokines, the
      quantitative levels of bacteremia, or the overall mortality rate following CLP.
      The results indicate that rPSGL-Ig did not exacerbate infection in these
      experimental sepsis models.

PMID- 11303729
TI  - Adenosine inhibits neutrophil vascular endothelial growth factor release and
      transendothelial migration via A2B receptor activation.
AB  - The effects of adenosine on neutrophil (polymorphonuclear neutrophils; PMN)
      directed changes in vascular permeability are poorly characterized. This study
      investigated whether adenosine modulates activated PMN vascular endothelial
      growth factor (vascular permeability factor; VEGF) release and transendothelial
      migration. PMN activated with tumour necrosis factor-alpha (TNF-alpha, 10 ng/mL)
      were incubated with adenosine and its receptor-specific analogues. Culture
      supernatants were assayed for VEGF. PMN transendothelial migration across human
      umbilical vein endothelial cell (HUVEC) monolayers was assessed in vitro.
      Adhesion molecule receptor expression was assessed flow cytometrically. Adenosine
      and some of its receptor-specific analogues dose-dependently inhibited activated
      PMN VEGF release. The rank order of potency was consistent with the affinity
      profile of human A2B receptors. The inhibitory effect of adenosine was reversed
      by 3,7-dimethyl-1-propargylxanthine, an A2 receptor antagonist. Adenosine (100
      microM) or the A2B receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA, 100
      microM) significantly reduced PMN transendothelial migration. However, expression
      of activated PMN beta2 integrins and HUVEC ICAM-1 were not significantly altered
      by adenosine or NECA. Adenosine attenuates human PMN VEGF release and
      transendothelial migration via the A2B receptor. This provides a novel target for
      the modulation of PMN-directed vascular hyperpermeability in conditions such as
      the capillary leak syndrome.

PMID- 11303728
TI  - Signal transduction events in Chinese hamster ovary cells expressing human CD14;
      effect of endotoxin desensitization.
AB  - Previous studies suggest that endotoxin (LPS) stimulation of CD14 receptors may
      be coupled to heterotrimeric G proteins. However, characterization of the G
      protein-coupled signaling pathways is incomplete. Also, specific changes in the
      transduction pathways occur in a phenomenon known as LPS tolerance or
      desensitization induced by prior exposure to LPS. In the present study, we
      examined potential CD14-dependent G protein-coupled signaling events in response
      to LPS, and changes in signaling in these pathways during LPS desensitization in
      Chinese Hamster Ovary (CHO) cells. LPS stimulated inhibitory kappa B alpha
      (IkappaB alpha) degradation and p38 phosphorylation in CHO cells transfected with
      human CD14 receptor (CHO-CD14), but not in CHO cells transfected with vector
      only. However, activation of these signaling events diverged early in the signal
      transduction pathways. Pretreatment with pertussis toxin, which inactivates
      inhibitor G protein (G alpha i) function, significantly inhibited LPS-induced p38
      phosphorylation, but not LPS-induced IkappaB alpha degradation. Mastoparan, a
      putative G alpha i agonist, synergized with LPS to induce p38 phosphorylation.
      Thus, LPS stimulation of p38 phosphorylation is, in part, G alpha i coupled,
      whereas IkappaB alpha degradation is not. In subsequent studies, CHO-CD14 cells
      were desensitized by prior LPS exposure. LPS-desensitized cells exhibited
      augmented IkappaB alpha content and were refractory to LPS-induced IkappaB alpha
      degradation and p38 phosphorylation. Pretreatment with cycloheximide, a protein
      synthesis inhibitor, prevented the effect of LPS desensitization on augmenting
      cellular IkappaB alpha content and its refractoriness to LPS-induced degradation.
      However, cycloheximide pretreatment did not prevent impaired p38 phosphorylation
      in desensitized cells. IkappaB alpha upregulation in LPS tolerance may occur
      through increased synthesis and/or induction of protein that suppress IkappaB
      alpha degradation. The latter protein synthesis-dependent mechanisms may be
      distinct from mechanismis inhibiting p38 phosphorylation in tolerance. These
      findings suggest that LPS tolerance induces CD14-dependent signaling alterations
      in G alpha i-coupled pathways leading to mitogen-activated (MAP) kinase
      activation as well as G alpha i-independent pathways inducing IkappaB alpha
      degradation.

PMID- 11303730
TI  - Blood transfusion and the two-insult model of post-injury multiple organ failure.
AB  - Neutrophils (PMNs) have been implicated in the pathogenesis of multiple organ
      failure (MOF). The two-insult model of MOF is based on the fundamental concept
      that two sequential and independent insults that are individually innocuous
      against the host can cause overwhelming inflammation. The in vitro PMN
      priming/activation sequence simulates the two-insult model. Our work has
      demonstrated that transfusion is an early consistent risk factor for post-injury
      MOF and lysophosphatidylcholines (lyso-PCs) are generated in stored blood
      components. Additionally, platelet-activating factor (PAF) is a key inflammatory
      agent produced in severely injured patients. We therefore hypothesize that two
      events, trauma and transfusion, enhance PMN cytotoxicity irrespective of the
      sequence. Superoxide (O2-) production was measured by reduction of cytochrome c,
      adherence to fibrinogen was assessed by the radioactivity of adherent Na2(51)CrO4
      (51Cr)-labeled PMNs, and endothelial cell (EC) damage by measuring the
      radioactivity released from 51Cr-labeled human umbilical vein endothelial cells
      monolayers. Isolated PMNs were primed with buffer, PAF (2 microM), or lyso-PCs
      (4.5, 15, and 30 microM) followed by activation with buffer, N-formyl-methionyl
      leucyl-phenylalanine (fMLP) (1 microM), PAF (2 microM), or lyso-PCs (4.5, 15, and
      30 microM). Neither PAF nor lyso-PCs alone stimulated O2- production. While PAF
      alone caused PMN adherence, lyso-PCs alone did not allowed PMNs to adhere to
      fibrinogen. However, both combinations of PAF/lyso-PCs and lyso-PCs/PAF
      significantly augmented O2- production and PMN adherence. Furthermore, these
      enhanced PMN cytotoxic responses significantly caused EC damage. These findings
      suggest that in the scenario of the two-insult model, early or late transfusion
      administered following trauma can provoke PMN cytotoxicity via priming or
      activation, thereby increasing the risk of post-injury MOF.

PMID- 11303731
TI  - Influence of hypertonic saline on bacterial translocation in controlled
      hemorrhagic shock.
AB  - Translocation of enteric bacteria has been described in rats following
      hemorrhagic shock (HS). The aim of the present study was to evaluate the effect
      of hypertonic saline (HTS) on bacterial translocation (BT) in the setting of
      controlled HS in rats. The study included 2 arms. Arm I was a qualitative
      assessment of translocation. Sixty-eight anesthetized animals were studied. The
      rats were divided into 5 groups. Group I (n = 10) was sham shock controls. In
      groups II-V, HS was induced by arterial bleeding to mean arterial pressure (MAP)
      of 35-45 mmHg, which was maintained for 30 min. The animals were then allocated
      into 4 groups: group II (n = 19) untreated HS; group III (n = 13) normal saline
      (NS) treated; group IV (n = 13) HTS-treated; and group V (n = 13) HTS and blood
      treated. Mesenteric lymph nodes, liver, spleen, portal, and systemic blood were
      sent for culture after 24 h. Translocation occurred if enteric bacteria were
      cultured from at least one site. Arm II was a quantitative assessment of
      translocation. Two groups were studied: untreated HS (n = 7) and HTS treated (n =
      6). In the qualitative arm, the 24-h mortality in untreated rats (group II) was
      31.5% compared to 5.1% in treated animals (groups II-V) (P = 0.01). No BT was
      detected in control animals (group I). BT after HS was not different between
      groups II, III, and IV (92.3%, 91.6%, and 100%, respectively). Group V showed
      fewer translocations than groups II-IV, a difference that was especially
      significant compared with group IV (P = 0.039). However, BT to distant sites
      (systemic blood and spleen) was significantly lower in group V than in groups II
      IV (P < 0.05). In the quantitative arm, the mortality rate was 16.7% in the
      untreated group. Although no qualitative significant difference in the
      translocation rate was found between the two groups (67% in untreated animals vs.
      50% in HTS treated), there was significant quantitative difference: in HTS
      treated group a significantly lesser bacteria translocated than in untreated
      animals (0.4 x 10(5) cfu/g vs. 4.2 x 10(5) cfu/g, respectively [P = 0.001]). We
      concluded that whereas assessed qualitatively, in this model of severe HS in
      rats, the hemorrhagic insult itself resulted in BT in most animals and treatment
      with NS, HTS, and blood resulted in reduced early mortality but did not alter
      significantly the translocation rate. Only the combination of HTS and blood
      resulted in reduced BT to distant sites. However, quantitative assessment showed
      that HTS significantly reduced the number of translocating bacteria.

PMID- 11303732
TI  - Divergent effects of ischemia/reperfusion and nitric oxide donor on TNFalpha mRNA
      accumulation in rat organs.
AB  - We previously showed that serum TNFalpha bioactivity in rats is proportional to
      the extent of graded tissue injury caused by laparotomy, intestinal ischemia, and
      reperfusion and that the spleen is an important source of TNFalpha secretion in
      this condition. TNFalpha production varies, depending on the type and duration of
      tissue injury. It is also affected by other mediators, such as nitric oxide (NO).
      TNFalpha is known to increase NO production, but the effect of NO on the
      production of TNFalpha has not yet been fully elucidated. In this study we
      determined the levels of TNFalpha mRNA in rat organs after graded injury caused
      by anesthesia, laparotomy, intestinal ischemia, and reperfusion and evaluated the
      effects of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) on it. Samples
      from different organs were removed, and TNFalpha gene expression was evaluated by
      semiquantitative RT-PCR. TNFalpha mRNA was not detected in the intestine (the
      ischemic organ) and in the kidney, brain, heart, or liver after all 4
      experimental protocols. In the mesenteric lymph node (draining the ischemic
      organ) a basal level of expression of TNFalpha mRNA was detected in the control
      (anesthesia alone) group, which was increased significantly after ischemia. In
      the spleen (a remote immune organ not directly involved in the ischemia), a
      significant gradual increase in TNFalpha mRNA, which correlated to the severity
      of the experimental protocol, was observed. In the lung (a central participant in
      post-injury multiple organ failure), all interventions increased TNFalpha mRNA.
      Infusion of SNAP exerted a differential effect on TNFalpha mRNA: diminished its
      accumulation in the lymph node, enhanced it in the lung, and had no effect in the
      spleen. The divergent organ pattern of TNFalpha transcription emphasizes the
      importance of its localized expression, which is critical to the understanding of
      its autocrine and paracrine actions in ischemia and reperfusion.

PMID- 11303733
TI  - TPN decreases IL-4 and IL-10 mRNA expression in lipopolysaccharide stimulated
      intestinal lamina propria cells but glutamine supplementation preserves the
      expression.
AB  - Total parenteral nutrition (TPN) decreases intestinal IgA and levels of Th2
      cytokines, interleukin (IL)-4, and IL-10 within the supernatants of intestinal
      homogenates. These cytokines are known to stimulate IgA production in vitro by
      cells of the gut-associated lymphoid tissue (GALT). Glutamine (GLN)
      supplementation of TPN normalizes GALT mass and cytokine levels. Because
      intestinal homogenates contain mucosa which itself is a source of cytokines, it
      was unclear whether cytokines change within the GALT itself. This study
      investigates dietary effects on IL-4 and IL-10 cytokine mRNA expression within
      isolated GALT lamina propria cells after lipopolysaccharide (LPS) stimulation.
      Prospective randomized experimental trials were used in this study. Fifty-nine
      mice were randomized to chow, intravenous TPN (IV-TPN), intragastric TPN (IG
      TPN), complex enteral diet (CED), or 2% GLN-supplemented TPN (GLN-TPN). In
      experiment 1, animals were fed chow, IV-TPN, IG-TPN, or CED for 5 days and
      received intraperitoneal LPS (100 microg/kg BW), and then were sacrificed 1 h
      later. Intestine was harvested for GALT lamina propria. Total RNA was extracted
      from lamina propria cells and cytokine mRNA for IL-4, and IL-10 was measured by
      reverse transcriptase polymerase chain reaction. IgA levels of intestinal washing
      were also measured with ELISA. In experiment 2, mRNA for IL-4 and IL-10, and
      intestinal IgA levels were measured in mice fed chow, IV-TPN, or GLN-TPN as in
      experiment 1. Both IL-4 and IL-10 mRNA expression decreased significantly in IV
      TPN mice compared to chow or CED feeding. IG-TPN resulted in IL-10 mRNA
      expression significantly lower than chow or CED but significantly better than IV
      TPN. GLN preserved IL-4 and IL-10 mRNA levels, which correlated with intestinal
      IgA levels. Route and type of nutrition as well as GLN influence message for the
      Th2 type IgA-stimulating cytokines, IL-4 and IL-10, within the primary site of
      GALT IgA production, the lamina propria.

PMID- 11303734
TI  - Pulmonary tissue factor mRNA expression during murine traumatic shock: effect of
      P-selectin blockade.
AB  - Tissue factor (TF) is the primary cellular initiator of the coagulation protease
      cascade and serves as a cell surface receptor and a specific cofactor for plasma
      factors VII/VIIa. Because there is evidence that TF is regulated by a P-selectin
      dependent gene, we examined TF mRNA expression in the lungs during murine
      traumatic shock in the presence and absence of recombinant soluble P-selectin
      glycoprotein ligand-1 (rsPSGL.Ig) by using ribonuclease protection assays.
      Moreover, we studied the level of TF mRNA expression in mice with their P
      selectin gene deleted (P-selectin -/-). Our data show that TF mRNA was
      significantly increased (+143%; P < 0.001) in the lungs 2 h after trauma compared
      with control rats subjected to sham trauma, which exhibited reduced TF mRNA
      expression (-34%; P < 0.001) after systemic administration of rsPSGL.Ig. The
      expression of TF mRNA was also significantly decreased (-29%; P < 0.05) in the
      lungs of P-selectin -/- mice compared with wild-type control C57B16 mice. The
      present results provide evidence for a P-selectin-dependent mechanism that
      enhances TF gene expression in traumatic shock. The major support for this
      mechanism is that either blockade of P-selectin by rsPSGL.Ig or deletion of the P
      selectin gene leads to significant decreases in TF mRNA expression in the lung.
      These results are consistent with the concept that TF interacting with P-selectin
      may play a significant role in the pathophysiology of trauma.

PMID- 11303735
TI  - The expression of G-protein-gated inwardly rectifying K+ channels GIRK1 and GIRK2
      mRNAs in the supraoptic nucleus of the rat and possible role involved.
AB  - The expression of G-protein-gated inwardly rectifying K channels subunits GIRK1
      and GIRK2 mRNAs in the supraoptic nucleus (SON) was investigated in the rat by in
      situ hybridization with non-radioactive dig-labeled cRNA probes. Double-labeled
      methods were used to study the co-localization of GIRK1 and 2 and oxytocin (OT)
      and vasopressin (AVP) in the SON. The present study revealed wide and intense
      expression of GIRK1 and GIRK2 mRNAs with high overlapping in the SON, indicating
      the heterologous channel of GIRK1/GIRK2 was a major functional channel in the
      SON. Given that 100% of OT-positive and 95% of (AVP)-positive neurons in the SON
      expressed GIRK1/GIRK2 mRNAs, it is possible that GIRK1/GIRK2 channel, activated
      through G-protein coupled receptors, may be involved in the inhibitory regulation
      of the release of OT and AVP from the SON.

PMID- 11303736
TI  - Melatonin delays photoreceptor degeneration in the rds/rds mouse.
AB  - Photoreceptors in retinitis pigmentosa (RP), a group of inherited retinal
      degenerative diseases, die through apoptosis. Since melatonin protects against
      neuronal apoptotic death, we tested its ability to slow photoreceptor
      degeneration in the rds/rds mouse, an animal model for RP. Shortly after birth,
      rds/rds mice were given daily i.p. injections of melatonin or vehicle for 11
      weeks. Melatonin treatment significantly delayed photoreceptor loss and reduced
      the number of apoptotic photoreceptors. Further studies should determine if
      melatonin will have potential for the treatment of certain human retinal
      degenerations.

PMID- 11303737
TI  - Embryonic brain precursors transplanted into kainate lesioned rat spinal cord.
AB  - Embryonic day 14 rat cerebral cortex-derived precursors were expanded with FGF2
      and labeled with BrdU prior to being transplanted into the kainic acid-lesioned
      adult rat spinal cord. While these precursors give rise to cells with neuronal,
      astrocytic and oligodendroglial phenotypes vitro, they remained largely
      undifferentiated up to 12 weeks in vivo. Numerous BrdU-labeled cells were found
      in injured gray matter, and also lining the dilated central canal that sometimes
      accompanies these lesions. BrdU-labeled cells never co-expressed Map2ab, rarely
      co-expressed GFAP but often co-expressed nestin, even after 12 weeks in vivo.
      These observations suggest that the environment of the kainic acid-injured spinal
      cord is not hostile to transplanted embryonic cerebral cortex-derived precursors,
      but also is not conducive to their neuronal differentation.

PMID- 11303738
TI  - Ischemia-induced inhibition of the initiation factor 2alpha phosphatase activity
      in the rat brain.
AB  - Rats were subjected to the standard four-vessel occlusion model of brain
      transient ischemia for 30 min. Following different recirculation periods, the
      level of phosphorylation of the initiation factor 2 subunit alpha (eIF2alpha) and
      the eIF2alpha kinase/s and phosphatase/s activity were determined. eIF2alpha
      phosphorylation significantly increased very early during reperfusion (10-30
      min), recovering at 4 h of reperfusion. Activation of any eIF2alpha kinases
      studied during ischemia or reperfusion was not noted. Conversely, eIF2alpha
      phosphatase activity significantly decreased at 10-15 min of reperfusion,
      reaching values even higher than in controls at 2-4 h of reperfusion. Our results
      support the hypothesis that the reperfusion-induced phosphorylated eIF2alpha
      changes are at least a result of the transiently eIF2alpha phosphatase
      inhibition.

PMID- 11303739
TI  - Immunohistochemical demonstration of L-serine distribution in the rat brain.
AB  - L-Serine has been suggested by in vitro studies to be an important neurotrophic
      factor which supports survival and neurite outgrowth of neurons. It is also a
      precursor of D-serine, a putative neurotransmitter. In the present study, we
      raised antibodies against L-serine in a rabbit and examined immunohistochemical
      distribution of the amino acid in the rat brain. In the hippocampus and the
      cerebellar cortex, where neurotrophic effects of L-serine have been indicated, L
      serine immunoreactivity was found primarily in astrocytes. In the brain stem,
      where neuronal distribution of D-serine was reported, positive staining for L
      serine was located primarily in neurons. Regional differences of cellular
      distribution of L-serine were indicated.

PMID- 11303741
TI  - Dopamine D2L receptor- and age-related reduction in offensive aggression.
AB  - The dopamine D2 receptor (D2) has been implicated in attention-deficit
      hyperactive disorder (ADHD) and aging. Two isoforms of D2 have been identified,
      termed D2L (long form) and D2S (short form). In this study, we investigated the
      role of D2L in offensive aggression, using mice lacking the dopamine D2L receptor
      (D2L-/-) as a model system and the resident-intruder test. We found that D2L-/-
      mice showed much lower levels of aggression than wild-type mice. Interestingly,
      offensive aggression also decreased as the age of the mice increased. These
      results suggest that both the D2L receptor and aging play roles in the modulation
      of offensive aggression. This finding may contribute to our understanding of the
      neurobiological basis of aggression.

PMID- 11303740
TI  - Topiramate promotes neurite outgrowth and recovery of function after nerve
      injury.
AB  - Topiramate is a structurally novel neurotherapeutic agent with a unique
      combination of pharmacological properties and currently is available in most
      world markets for treating several seizure disorders. Because its pharmacological
      profile was suggestive of possible activity as a neuroprotectant, topiramate was
      evaluated and found to be active in several animal models of stroke or
      neuropathic pain. This prompted an evaluation of topiramate as a possible
      neurotrophic agent. In this study, topiramate enhanced the recovery of facial
      nerve function after injury when administered orally at therapeutically relevant
      doses, and significantly increased neurite outgrowth in cell cultures derived
      from fetal rat cortical and hippocampal tissues.

PMID- 11303742
TI  - NADPH diaphorase is developmentally regulated in rat olfactory epithelium.
AB  - In vertebrate olfactory receptor neurons, NO synthase (NOS) has been detected in
      embryonic and early postnatal stages. However, expression of the enzyme in the
      mature epithelium is still controversial. We analyzed the developmental
      expression pattern of the histochemical NOS-marker NADPH diaphorase (NADPHd) in
      the olfactory epithelium of young rats. NADPHd was expressed in a small subset of
      olfactory receptor neurons as early as P0. Between P0 and P24 the number of
      labeled neurons increased 10-fold, stabilizing thereafter. Whereas NADPHd was
      generally found in the somata, a transitory dendritic expression was observed
      between P2 and P5. This dynamic postnatal regulation of the cellular distribution
      of NADPHd appears to reflect developmental processes within the olfactory
      epithelium.

PMID- 11303743
TI  - The antioxidant enzyme quinone reductase is up-regulated in vivo following
      cerebral ischemia.
AB  - An astrocyte antioxidant enzyme, quinone reductase (QR), was studied in vivo to
      assess whether its activity was up-regulated following cerebral ischemia. Rats
      were given a unilateral focal cerebral infarct and regions of interest within the
      ischemic penumbra compared to the non-ischemic side for QR activity. At 7 days
      post-ischemia, QR activity was significantly up-regulated within cells of
      astrocyte morphology in the cortex (p = 0.007) and subcortical (p = 0.005) areas
      adjacent to the infarct. This enzyme activity peaked at 7 days but was still
      significantly up-regulated at 14 days. Up-regulation of QR activity occurs within
      the ischemic penumbra of a stroke in this animal model and may contribute to
      factors that limit ischemic damage to neurons in this area.

PMID- 11303744
TI  - Nuclear factor-kappaB activation is not involved in a MPTP model of Parkinson's
      disease.
AB  - In the present study the involvement of hydroxyl free radicals and nuclear factor
      kappaB (NF-kappaB) activation was investigated in the MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine) model of Parkinson's disease. MPTP (30 mg/kg, s.c.)
      produced a significant 2-fold increase in hydroxyl free radicals in the striatum
      of C57BL/6 mice determined by microdialysis in combination with the salicylate
      hydroxylation assay. Electrophoretic mobility shift assays did not detect NF
      kappaB activation after MPTP treatment. Furthermore, p50-deficient mice showed
      only minor differences in striatal dopamine and metabolite levels as well as
      tyrosine hydroxylase immunoreactivity after MPTP administration in comparison to
      wildtype mice. We postulate that, although hydroxyl radical production was
      enhanced, NF-kappaB plays only a minor role in the MPTP model because neither
      neurochemical nor immunocytochemical parameters were altered in p50-deficient
      mice in comparison to controls.

PMID- 11303745
TI  - Increased expression of synaptophysin and stathmin mRNAs after methamphetamine
      administration in rat brain.
AB  - The rearrangement of neural networks associated with the behavioral sensitization
      induced by psychostimulants is poorly understood. We have investigated the effect
      of methamphetamine (METH) administration on the mRNA levels of three different
      classes of plasticity-related genes in the rat brain. The expression of
      synaptophysin mRNA increased 20-40% in the nucleus accumbens, prefrontal and
      temporal cortices, 1-24 h after acute METH administration, and that of stathmin
      mRNA increased about 20% in the prefrontal cortex 1 h later. They did not change
      after subchronic administration. The level of alpha-tubulin mRNA was constant.
      Therefore, synaptophysin and stathmin play an important role in the neural
      plastic changes involved in the early induction process of METH-induced
      sensitization, but not in the later maintenance process.

PMID- 11303746
TI  - Axonal projection of olfactory sensory neurons during the developmental and
      regeneration processes.
AB  - We have studied the projection of olfactory sensory neurons (OSNs), during the
      developmental and regeneration processes, using the transgenic mouse carrying the
      differently tagged odorant receptor genes, MOR28. We have found that the axon
      terminals of the two sets of MOR28-positive OSNs, one expressing the lacZ tag and
      the other expressing the green fluorescent protein gene, are dispersed and
      intermingled at early developmental or regeneration stages. Projection areas
      become more distinct and separated at later stages, however, two sets of axon
      fibers are not typically bundled or segregated during pathfinding. It appears
      that segregation of axons mainly occurs when they target at the olfactory bulb to
      form the glomerular structure.

PMID- 11303747
TI  - Analysis of effects and pharmacokinetics of subcutaneously administered BDNF.
AB  - Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family and
      has been shown to be a potent and effective trophic factor for motor neurons and
      other neurons of the peripheral and central nervous. Little is known, however,
      about the relationship between the efficacy and pharmacokinetics of s.c.
      administered BDNF. In this study, the efficacy of BDNF on motor neuron protection
      in sciatic or facial nerve axotomy models was examined and compared with the
      concommitant concentrations of BDNF in plasma. Delayed treatment (started at 1
      week after surgery) of BDNF was also shown to retard choline acetyltransferase
      reduction in sciatic nerve axotomy models.

PMID- 11303748
TI  - Tenascin and laminin function in target recognition and central synaptic
      differentiation.
AB  - The influence of the target cell-issued extracellular molecules tenascin-C and
      laminin on synaptogenesis was studied in mixed primary cultures of pituitary
      melanotrophs and hypothalamic neurons. We could demonstrate in this neuron-target
      co-culture system a new role for tenascin-C, which appeared to be expressed as an
      early and transitory signal of target recognition for selective afferent fibers.
      Tenascin-C expression disappeared from the melanotrophs soon after the
      establishment of neural contacts. Concomitantly, the melanotrophs became
      immunoreactive for laminins, and more specifically for the synaptic isoform beta2
      chain-containing laminin. The laminin signal appeared to be involved in the
      induction of synaptic differentiation, selectively with fibers containing both
      dopamine and GABA, like those innervating the melanotrophs in situ.

PMID- 11303749
TI  - Isoflurane enhances glutamate uptake via glutamate transporters in rat glial
      cells.
AB  - In this study I examined whether isoflurane, an inhalational anesthetic used
      commonly in clinical practice, affected glutamate uptake via glutamate
      transporters, proteins expressed in the plasma membrane of cells in the central
      nervous system. Isoflurane at clinically relevant concentrations (1-3%) caused a
      time-, sodium- and concentration-dependent increase of glutamate uptake in
      primary cultures of rat cerebral mixed glial cells. This enhancement was
      inhibited by a specific glutamate transporter inhibitor. The study also
      demonstrated that 2.0% isoflurane significantly increased both Vmax and Km of
      transporter-mediated glutamate uptake. Thus, isoflurane enhances glutamate uptake
      by a pathway that requires function of glutamate transporters. This represents a
      novel pharmacological effect of inhalational anesthetics and may contribute to
      isoflurane-induced anesthesia and neuroprotective effects.

PMID- 11303750
TI  - IL-6 up-regulates CNTF mRNA expression and enhances neurite regeneration.
AB  - Interleukin-6 (IL-6) is a neurotrophic cytokine, however, its direct effect on
      nerve regeneration has not been well characterized. We therefore examined the
      effect of IL-6 on neurite regeneration using the rat dorsal root ganglion. IL-6
      significantly enhanced neurite regeneration from transected nerve terminals. We
      also examined the mRNA expression of IL-6 family cytokines and their receptors
      during the regeneration. The mRNA expressions of IL-6, IL-6 receptor, leukemia
      inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) receptor alpha, and
      LIF receptor beta showed no significant differences by the addition of IL-6. In
      contrast, IL-6 enhanced the mRNA expression of gp130 and CNTF. In addition, CNTF
      significantly increased neurite regeneration when added exogenously. Our data
      suggest that IL-6 enhanced regeneration via up-regulating CNTF expression.

PMID- 11303751
TI  - Localization of neurotensin NTS2 receptors in rat brain, using.
AB  - The brain localization of the neurotensin receptor NTS2 was studied with
      [3H]levocabastine, using an autoradiographic procedure. This study suggests that
      NTS2 receptors are mainly intracellular. High densities of binding sites were
      observed in the cingulate, insular, temporal, occipital, enthorhinal cortex,
      amygdaloid complex, septohippocampal nuclei, medial thalamus, mammillary bodies
      and superior colliculi; a moderate labelling was observed in the anterior and
      medial hippocampus, olfactory tubercle, hypothalamus, periaqueductal gray matter,
      caudate putamen, nucleus accumbens, septum, lateral thalamus, dorsal raphe
      nucleus and cerebellum; finally, a low labelling was apparent in the ventral
      tegmentum area and substantia nigra. Thus it appears that NTS2 receptors are
      particularly abundant in the cerebral cortex, the limbic areas and some areas
      involved in pain perception.

PMID- 11303752
TI  - Differential effects of lovastatin treatment on brain cholesterol levels in
      normal and apoE-deficient mice.
AB  - Growing evidence indicates that membrane cholesterol is involved in the
      development of Alzheimer's disease. Therefore, the availability of
      pharmacological strategies to modify brain cholesterol is of increasing
      importance. Accordingly, we investigated the effects of the HMG-CoA reductase
      inhibitor lovastatin on brain cholesterol levels in vivo. Brain cholesterol was
      significantly decreased by lovastatin treatment (100 mg/kg/day) in 1- and 12
      month-old C57BL/6J mice. Reduced brain cholesterol was associated with decreased
      pyrene-excimer fluorescence, indicating altered membrane function. Lovastatin had
      no effect on brain cholesterol ApoE-/- mice. Peripheral cholesterol levels were
      not affected by lovastatin in all three groups of mice. We demonstrate for the
      first time that lovastatin represents a valid pharmacological tool to
      significantly modulate brain cholesterol levels.

PMID- 11303753
TI  - Glucocorticoid receptors and serotonin N-acetyltransferase activity in the fish
      pineal organ.
AB  - This study aimed to determine whether glucocorticoid receptors are expressed in
      the photosensitive trout pineal organ, and whether glucocorticoids modulate
      melatonin secretion. On Western blots from pineal extracts, an antibody directed
      against trout glucocorticoid receptor labeled a single band at the expected size
      (approximately 100 kDa). Dexamethasone inhibited pineal arylalkylamine N
      acetyltransferase activity (AANAT2; serotonin --> N-acetylserotonin) in a dose
      dependent manner after 6 h of culture in the dark (IC50 2.10(-8) M). RU486 (10(
      7) M) alone had a partial agonistic activity, whereas it antagonized the effects
      of 10(-8) M dexamethasone. Hydroxyindole-O-methyltransferase activity (N
      acetylserotonin --> melatonin) remained unaffected. This is the first
      demonstration that glucocorticoid receptors are present in the pineal organ and
      that glucocorticoids modulate melatonin production.

PMID- 11303754
TI  - Axillary pheromones modulate pulsatile LH secretion in humans.
AB  - We examined the effect of axillary compounds on pulsatile secretion of serum
      luteinizing hormone (LH). Axillary compounds were collected from donor women in
      the follicular phase (FP) and the ovulatory phase (OP) and were treated with
      isopropyl alcohol (IPA). The recipient was not exposed to either axillary
      compounds or IPA for the first 4 h and was exposed to FP or OP compounds, or to
      IPA, during the next 4 h. The frequency of the LH pulse was increased by FP
      compounds and was decreased by OP compounds, but the LH pulse frequency was not
      changed by IPA. Therefore, in humans, pheromones may play a role in the
      modulation of the timing of ovulation by changing the frequency of pulsatile LH
      secretion.

PMID- 11303755
TI  - c-Jun N-terminal kinase activation in hippocampal CA1 region was involved in
      ischemic injury.
AB  - To clarify the role of c-Jun N-terminal kinase (NK) activation in brain ischemia,
      temporospatial alteration of active (diphosphorylated) JNK1/2 immunoreactivity in
      hippocampus after brain ischemia in rat was investigated. Western immunoblot
      study showed that JNK1/2 diphosphorylation level was increased biphasically in
      CA1 but not CA3/dentate gyrus (DG) after 10 min of ischemia. Cerebral ventricular
      infusion of JNK1/2 antisense oligonucleotides not only significantly decreased
      JNK1/2 protein expression and the activation level but also significantly
      decreased CA1 pyramidal cell death (demonstrated by cresyl violet staining) and
      DNA fragmentation (demonstrated by in situ end-labeling of DNA). These results
      suggest that JNK1/2 were selectively activated and involved in the selective cell
      death in hippocampal CA1 subfield after cerebral ischemia.

PMID- 11303756
TI  - Gestalt perception modulates early visual processing.
AB  - We examined whether early visual processing reflects perceptual properties of a
      stimulus in addition to physical features. We recorded event-related potentials
      (ERPs) of 13 subjects in a visual classification task. We used four different
      stimuli which were all composed of four identical elements. One of the stimuli
      constituted an illusory Kanizsa square, another was composed of the same number
      of collinear line segments but the elements did not form a Gestalt. In addition,
      a target and a control stimulus were used which were arranged differently. These
      stimuli allow us to differentiate the processing of colinear line elements
      (stimulus features) and illusory figures (perceptual properties). The visual N170
      in response to the illusory figure was significantly larger as compared to the
      other collinear stimulus. This is taken to indicate that the visual N170 reflects
      cognitive processes of Gestalt perception in addition to attentional processes
      and physical stimulus properties.

PMID- 11303757
TI  - Increased risk for frontotemporal dementia through interaction between tau
      polymorphisms and apolipoprotein E epsilon4.
AB  - The tau gene has an important role in frontotemporal dementia (FTD) as pathogenic
      mutations have been found in hereditary forms of the disease. Furthermore, a
      certain extended tau haplotype has been shown to increase the risk for
      progressive supranuclear palsy, corticobasal degeneration, Parkinson's disease
      and, in interaction with the apolipoprotein E (apoE) epsilon4 allele, Alzheimer's
      disease. By microsatellite analysis we investigated an intronic tau polymorphism,
      in linkage disequilibrium with the extended tau haplotype, in FTD patients (n =
      36) and healthy controls (n = 39). No association between any of the tau
      alleles/genotypes and FTD was seen, but certain tau alleles and apoE epsilon4
      interactively increased the risk of FTD (p = 0.006). We thus propose that this
      extended tau haplotype in combination with apoE epsilon4 is a genetic risk factor
      for FTD.

PMID- 11303758
TI  - 5-HT receptor blockade in the posterior amygdala elicits feeding in female rats.
AB  - Previous work suggests that feeding following intraventricular (i.v.t.)
      injections of the serotonin (5-HT)(1/2/7) antagonist metergoline (MET) is not
      localized to the hypothalamus. Since lesions of the posterior basolateral
      amygdala (pBLA) block feeding following systemic 5-HT1A agonist 8-hydroxy-2(di-n
      propylamino)tetralin, the ability of intra-pBLA MET to elicit feeding was
      investigated. In two separate experiments, feeding of female rats was measured
      over 2 h following 0, 3, 10 and 30 nmol and 0, 0.03, 0.3 and 3 nmol MET (mol. wt.
      403.5) injected bilaterally into each pBLA. All three doses used in Experiment 1
      increased feeding over 2 h. In Experiment 2, feeding over the first hour was
      enhanced after the two highest doses. Since intra-pBLA MET elicits feeding
      comparable to that seen using much higher doses administered i.v.t. these data
      implicate the pBLA as an extra-hypothalamic site mediating the effects of 5-HT in
      feeding control.

PMID- 11303759
TI  - Acetylsalicylic acid reduces ischemia-induced proliferation of dentate cells in
      gerbils.
AB  - Transient global ischemia causes neurogenesis in the dentate gyrus of adult
      rodents. Ischemic insults to rodents also induce cyclooxygenase-2 (COX-2), an
      isoform of cyclooxygenases (COXs) and a rate-limiting enzyme for prostanoid
      synthesis. In the present experiments, adult Mongolian gerbils were chronically
      treated with acetylsalicylic acid (ASA), a non-selective COX inhibitor, and the
      proliferation of cells in the dentate gyrus was examined under ischemia. It was
      proved that BrdU-labeled cells in the dentate gyrus were significantly reduced in
      number following ASA treatment after 10 min global ischemia. The result strongly
      suggests that COX, probably COX-2, and prostanoids play an important role in the
      proliferation of neural cells after ischemia in gerbils.

PMID- 11303760
TI  - BDNF mediates the neuroprotective effect of PACAP-38 on rat cortical neurons.
AB  - In primary cultures from rat cerebral cortex, pituitary adenylate cyclase
      activating polypeptide (PACAP-38) exerted a protective effect on cell death
      induced by the excitotoxin NMDA in neuron-enriched cultures and also on apoptotic
      cell death induced by serum deprivation in mixed neuronal-glial cultures. The
      neuroprotective effect was already observed at subnanomolar concentrations of
      PACAP and was slightly more pronounced against excitotoxic cell death. BDNF
      protein expression was reduced by NMDA and much more markedly by serum
      deprivation (approximately 28 and 93% reduction respectively). In both cellular
      injury conditions, the diminished BDNF expression was significantly prevented by
      PACAP. When purified neuronal cultures were preincubated with an antiserum anti
      BDNF, at a concentration without any intrinsic effect on cell viability, the
      neuprotective effect of PACAP was no longer observed. The results suggest that
      the neuroprotective effect of PACAP-38 is mediated, at least in part, by
      preventing the suppressed expression of a neurotrophin essential for cortical
      neuron survival.

PMID- 11303761
TI  - Increased Fos induction in adult rats that experienced neonatal peripheral
      inflammation.
AB  - The response to noxious stimulation was compared in adult rats that had
      peripheral inflammation as neonates and untreated rats. On postnatal day 1, rat
      pups experienced complete Freund's adjuvant (CFA)-induced inflammation of the
      left hind paw. At 8 weeks of age, these rats and neonatal untreated rats received
      a bilateral injection of CFA into their hind paws. Fos-like immunoreactivity (Fos
      LI) was used as a measure of neuronal activity in dorsal horn nociceptive
      pathways. A significant increase in Fos-LI was found on the left side of the
      lumbar spinal cord of neonatal treated rats as compared to neonatal untreated
      rats. These results suggest that the experience of neonatal peripheral
      inflammation may result in an increase in the response of spinal cord neurons to
      peripheral inflammation as adults.

PMID- 11303762
TI  - Reduction in anti-apoptotic protein Bcl-2 in autistic cerebellum.
AB  - Autism is a neurodevelopmental disorder with genetic and environmental
      etiologies. Neurohistologic findings have shown Purkinje cell depletion and
      atrophy in the cerebellum of autistic subjects. We hypothesized that apoptotic
      mechanisms might explain these Purkinje cell findings. Bcl-2 is a potent anti
      apoptotic regulatory protein, which is reduced in schizophrenic brains. Autistic
      and normal control cerebellar cortices matched for age, sex and PMI were prepared
      for SDS-gel electrophoresis and Western blotting using specific anti-Bcl-2
      antibodies. Quantification of Bcl-2 showed a significant 34-51% reduction in
      autistic cerebellum (mean (+/- s.d.) optical density/75 microg protein 0.290 +/-
      0.08, n = 5) compared with controls (0.595 +/- 0.31, n = 8; p < 0.04); levels of
      neuronal-specific class III beta-tubulin (controls 49.8 +/- 6.7; autistics 36.2
      +/- 18.2), or beta-actin (controls 7.3 +/- 2.7; autistics 6.77 +/- 0.66) in the
      same homogenates did not differ significantly between groups. These results
      indicate for the first time that autistic cerebellum may be vulnerable to pro
      apoptotic stimuli and to neuronal atrophy as a consequence of decreased Bcl-2
      levels.

PMID- 11303763
TI  - Intracellular processing of aggregated tau differs between corticobasal
      degeneration and progressive supranuclear palsy.
AB  - Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are
      sporadic neurodegenerative diseases with intracytoplasmic aggregates of the
      microtubule-associated protein, tau, in neurons and glial cells. Immunoblot
      analysis of detergent-insoluble brain extracts of patients with CBD and PSP shows
      distinctive patterns of tau fragments. These results suggest differing
      intracellular processing of aggregated tau in these two diseases despite an
      identical composition of tau isoforms. Such biochemical differences may be
      related to the neuropathological features of these diseases.

PMID- 11303764
TI  - Time estimation in patients with right or left medial-temporal lobe resection.
AB  - Patients with either left or right antero-medial-temporal lobe (MTL) resection
      were investigated as to their ability to reproduce and produce three durations
      (5, 14, or 38 s) in three conditions (silence, counting, articulatory
      suppression). The results showed that patients with unilateral MTL lesions did
      not differ from controls when they had to encode the duration of a visual
      stimulus in order to reproduce it. By contrast, patients with right MTL lesions
      underestimated all three durations, compared with controls and with patients with
      left MTL resection, when they had to produce durations given in chronometric
      units. This finding suggests that the right MTL retains long-term representations
      of the conventional units necessary to the accurate production of durations.

PMID- 11303765
TI  - Testosterone regulates alpha-synuclein mRNA in the avian song system.
AB  - Alpha-synuclein is a small, highly conserved protein in vertebrates that has been
      linked to several neurodegenerative diseases. The avian song control system is
      one of the model systems in which the protein was independently discovered. Alpha
      synuclein is dynamically regulated in the song system during song learning, a
      process in which sex steroids play a central role. We compared alpha-synuclein
      mRNA expression in the brains of 12 adult male chipping sparrows (Spizella
      passerina) treated with either testosterone or blank s.c. implants. We saw
      pronounced upregulation of alpha-synuclein mRNA in, as well as an increase in the
      volume of, the song control nucleus area X in response to exogenous testosterone.
      To our knowledge this is the first report of steroid regulation of synuclein gene
      expression in any model system.

PMID- 11303766
TI  - Insulin inhibits voltage-dependent calcium influx into rod photoreceptors.
AB  - Insulin inhibits the ERG b-wave and modulates L-type calcium currents (I(Ca)) in
      various preparations. We therefore examined insulin's effects on I(Ca) and
      depolarization-evoked [Ca2+]i increases in rod photoreceptors. Insulin inhibited
      I(Ca) and caused a dose-dependent reduction in the depolarization-evoked Ca2+
      influx with an EC50 of 2.1 nM. Tyrosine kinase inhibitors, lavendustin A (100 nM)
      and genistein (10 microM), prevented insulin from reducing the depolarization
      evoked Ca2+ increase in rods. Their less active analogues, lavendustin B and
      daidzein, had similar effects. An insulin receptor-specific tyrosine kinase
      inhibitor, HNMPA-(AM)3 (50 microM), prevented insulin (30 nM) from reducing the
      depolarization-evoked Ca2+ increase in rods. The results suggest that insulin
      inhibits Ca2+ influx through voltage-dependent I(Ca) in rod photoreceptors via
      tyrosine kinase activity.

PMID- 11303767
TI  - MK-801 prevents dopamine D1 but not serotonin 2A stimulation of striatal
      preprotachykinin mRNA expression.
AB  - We examined dopamine (DA) and serotonin (5-HT) receptor-mediated influences on
      striatal preprotachykinin (PPT, tachykinin precursor) mRNA regulation in
      organotypic slice cultures. A 3 h exposure to SKF-38393 (10 microM, DA D1
      agonist) or DOI (10 microM, 5-HT2 agonist) increased PPT mRNA levels to 196.4%
      and 154.0%, respectively. Responses to SKF-38393 were prevented by SCH-23390 (10
      microM, D1 antagonist) whereas DOI-stimulated increases were prevented by
      ketanserin (10 microM, 5-HT2A antagonist). Since striatal tachykinin neurons also
      possess NMDA receptors that regulate gene expression, stimulation of PPT message
      levels was examined in the presence of MK-801, a non-competitive NMDA antagonist.
      Alone, MK-801 (10 nM) did not significantly alter basal PPT message levels.
      However, MK-801 prevented SKF-38393-stimulated increases in PPT mRNA expression
      while DOI-induced expression was not affected. These results provide evidence
      that D1 regulation of striatal tachykinin expression is dependent on NMDA-type
      glutamate neurotransmission while 5-HT2A regulation appears independent.

PMID- 11303768
TI  - Structural and functional cortical abnormalities after upper limb amputation
      during childhood.
AB  - Functional reorganization has been well documented in the human adult brain after
      amputation of the arm. To assess the effects of amputation on the developing
      brain, we investigated six patients with upper limb amputation in early childhood
      and one with right dysmelia. Transcranial magnetic stimulation indicated
      contralateral cortical disinhibition and enlargement of the excitable area of the
      stump. FMRI data corroborated these plastic changes and also showed an
      ipsilateral functional reorganization. In the T1-weighted MRI, we found
      structural deformities of the contralateral and ipsilateral central sulcus in
      three patients and a contralateral atrophic parietal lobule in two patients.
      Therefore, arm amputation in childhood affects functional organization as well as
      anatomical structure in both hemispheres.

PMID- 11303769
TI  - 5-Hydroxytryptamine attenuates free radical injury in primary mouse cortical
      cultures.
AB  - The effects of 5-hydroxytryptamine (5-HT) on several types of neuronal injury in
      mouse cortical cell cultures were tested. Co-treatment with 5-HT prevented free
      radical-mediated neuronal necrosis induced by FeCl2 or buthionine sulfoximine
      (BSO) in a dose-dependent manner. Subtype antagonists did not reverse the
      protective effect and 5-HT showed direct free radical scavenging activity
      evidenced by its ability to reduce the stable free radical 1,1-diphenyl-2
      picrylhydrazyl (DPPH) in a cell-free system. Excitotoxic necrosis induced by NMDA
      or apoptosis induced by staurosporine was not sensitive to 5-HT treatment. These
      features raise the possibility that the endogenous neurotransmitter 5-HT may work
      as an innate antioxidant defense mechanism in the CNS.

PMID- 11303770
TI  - Effect of serotonin depletion on nitric oxide induced cerebrovascular nociceptive
      response.
AB  - The study was conducted to investigate the effect of serotonin depletion on
      nitric oxide-induced meningeal vascular response and cerebrovascular nociception.
      Nitroglycerin was infused i.v. to control and serotonin-depleted rats. Pial
      circulation was monitored by intravital fluorescent videomicroscopy and Fos
      immunoreactivity trigeminal nucleus caudalis neurons was used as an indicator for
      the cerebrovascular nociception. The results showed that the degree of nitric
      oxide-induced pial microvascular dilatation was significantly greater in the
      serotonin-depleted group than the control. The number of nitric oxide-evoked Fos
      immunoreactive cells between the two groups remained comparable. The results
      suggest that though depletion of serotonin can facilitate the vascular response
      to nitric oxide it does not alter the nitric oxide-induced craniovascular
      nociceptive response.

PMID- 11303771
TI  - Cortical plasticity of spatial stimulus-response associations:
      electrophysiological and behavioral evidence.
AB  - Right-handed subjects tend to respond faster to stimuli presented in the visual
      hemifield that spatially corresponds to the responding hand. In a typical Simon
      task, response is based on a non-spatial salient feature of the stimulus (e.g.
      color) whereas its position must be ignored. However, the spatial position of the
      stimulus interferes with the processing of the salient characteristic. Subjects
      are significantly faster when stimulus side and response side correspond
      (corresponding condition) than when they do not (non-corresponding condition). We
      have previously shown with behavioral experiments that, when subjects practice
      reversed contingencies (that is, spatially incompatible trials) in a session
      preceding the Simon task, they show a long-term retention of these associations,
      resulting in the disappearance of the latency cost typically observed in non
      corresponding trials. Here we show, by means of the lateralized readiness
      potential, that the neural correlate of such behavioral plasticity is an increase
      in premotor cortex activation during preparation of non-corresponding responses.
      This effect showed a marked left-right asymmetry which suggests an important role
      of subjects' handedness. Our results demonstrate that humans can learn in a
      single session to reverse relatively stable stimulus-response associations.

PMID- 11303772
TI  - Soluble guanylyl cyclase is localized at the neuromuscular junction in human
      skeletal muscle.
AB  - Soluble guanlylyl cyclase (sGC) seems to be involved in mechanisms for rapid
      translation of electrical and chemical signals at the neuromuscular junction. To
      explore the cellular localization of the alpha2, alpha1 and beta1 subunits of
      sGC, we studied normal and denervated human muscle biopsies immunohistochemically
      using antibodies directed against the alpha2 and alpha1/beta1 subunits of sGC and
      performed double labellings with alpha-bungarotoxin. Confocal imaging could
      localize the alpha2 and alpha1/beta1 subunits of sGC at neuromuscular junctions
      and vessels and the subunits remained concentrated at neuromuscular junctions
      following denervation. The presence of sGC at neuromuscular junctions and at
      vessels suggests sGC could serve as a postsynaptic second messenger for fine
      tuning of nerve-muscle interaction and dynamic regulation of intramuscular blood
      flow.

PMID- 11303773
TI  - Adenosine A2A receptor knockout mice are partially protected against drug-induced
      catalepsy.
AB  - Catalepsy assessed using the bar test was measured in both adenosine A2A receptor
      knockout (A2AR KO) and wild-type (A2AR WT) mice submitted to acute administration
      of the dopamine D2 receptor antagonist haloperidol (0.5, 2, 4, 6 mg/kg i.p.), the
      dopamine D1 antagonist SCH 23390 (0.3-3 mg/kg, s.c.), the vesicular monoamine
      transporter blocker reserpine (3-5 mg/kg, s.c.) or the acetylcholine muscarinic
      receptor agonist pilocarpine (25-50 mg/kg, i.p.). Except for reserpine, catalepsy
      scores were significantly lower in A2AR KO mice than in A2AR WT mice following
      low doses of these cataleptogenic agents. These results suggest that adenosine
      A2A receptors influence not only dopamine D2 and D1 receptor-mediated
      neurotransmission but also acetylcholine muscarinic receptor-mediated
      neurotransmission.

PMID- 11303774
TI  - Effects of anisomycin on LTP in the hippocampal CA1: long-term analysis using
      optical recording.
AB  - Long-term potentiation (LTP) in the hippocampal CA1 region and in the dentate
      gyrus consists of different stages: early LTP lasting minutes or several hours,
      and late LTP lasting longer than 4 h. It has been suggested that the late phase
      of LTP is dependent on protein synthesis. However, the experimental results of
      the effects of protein synthesis inhibitors are still confusing. We applied
      optical recording techniques to rat hippocampal slices, and re-evaluated the
      effects of a protein synthesis inhibitor, anisomycin, on LTP. Using a voltage
      sensitive oxonol dye, NK3630 (RH482), LTP in the CA1 region could be monitored
      optically for a long-term period (7-8 h). In the presence of anisomycin, the
      potentiation of the EPSP (excitatory postsynaptic potential) lasted about 2-3 h,
      followed by a gradual decline in the signal amplitude. Statistically, significant
      effects of anisomycin were observed 6 h after LTP induction for 100 Hz tetanus
      and 8 h after LTP induction for 400 Hz tetanus. These results suggest that the
      early phase of LTP is independent of protein synthesis, while the late phase of
      potentiation (> 3-5 h) depends on protein synthesis.

PMID- 11303775
TI  - Changes in CSF hypocretin-1 (orexin A) levels in rats across 24 hours and in
      response to food deprivation.
AB  - Hypocretin-1 is consistently detectable in the CSF of healthy human subjects, but
      is absent in narcoleptics. However, functional roles of CSF hypocretin are
      largely unknown. We examined fluctuation of CSF hypocretin-1 across 24 h and in
      response to food restriction in rats. Hypocretin-1 levels were high during the
      dark period when animals were active, but decreased by 40% toward the end of the
      light (rest) period. After 72 h food deprivation hypocretin-1 levels during the
      rest phase increased to concentrations similar to those seen during the baseline
      active phase; however, no increase in response to food deprivation was observed
      during the active phase. These results indicate an important link between
      circadian control of sleep and energy homeostasis via the hypocretin system.

PMID- 11303776
TI  - How the mass counts: an electrophysiological approach to the processing of
      lexical features.
AB  - Nouns may refer to countable objects such as tables, or to mass entities such as
      rice. The mass/count distinction has been discussed in terms of both semantic and
      syntactic features encoded in the mental lexicon. Here we show that event-related
      potentials (ERPs) can reflect the processing of such lexical features, even in
      the absence of any feature-related violations. We demonstrate that count (vs
      mass) nouns elicit a frontal negativity which is independent of the N400 marker
      for conceptual-semantic processing, but resembles anterior negativities related
      to grammatical processing. This finding suggests that the brain differentiates
      between count and mass nouns primarily on a syntactic basis.

PMID- 11303777
TI  - Presidential election and cell recount.

PMID- 11303778
TI  - VIP and peptides related to activity-dependent neurotrophic factor protect PC12
      cells against oxidative stress.
AB  - Oxidative stress is a common associative mechanism that is part of the
      pathogenesis of many neurodegenerative diseases. Vasoactive intestinal peptide
      (VIP) is a principal neuropeptide associated with normal development and aging.
      We have previously reported that VIP induced the secretion of proteins from glial
      cells, including the novel survival-promoter: activity-dependent neurotrophic
      factor (ADNF). ADNF-9, a nine amino acid peptide derived from ADNF, protects
      neurons from death caused by various toxins. In the present study, we examined
      the neuroprotective effect of VIP against oxidative stress in a pheochromocytoma
      cell line (PC12). In addition, a lipophilic derivative of VIP, Stearyl-Nle17-VIP
      (SNV), and two femtomolar-acting peptides: ADNF-9 and a 70% homologous peptide to
      ADNF-9, NAP were tested as well. PC12 cells were treated with 100 microM H2O2 for
      24 h resulting in a reduction in cell survival to 35-50% as compared to controls.
      Addition of VIP or SNV prior and during the exposure to100 microM H2O2 increased
      cell survival to 80-90% of control values. Culture treatment with ADNF-9 or NAP
      in the presence of 100 microM H2O2 increased cell survival to 75-80% of control
      values. Messenger RNA expression analysis revealed that incubation with VIP
      resulted in a twofold increase in VIP mRNA, whereas NAP treatment did not cause
      any change in VIP expression, implicating different mechanisms of action.
      Furthermore, addition of an ADNF-9 antibody prevented the ability of VIP to
      protect against oxidative stress, suggesting that VIP protection is partially
      mediated via an ADNF-like protein.

PMID- 11303779
TI  - VIP-Related protection against lodoacetate toxicity in pheochromocytoma (PC12)
      cells: a model for ischemic/hypoxic injury.
AB  - To evaluate the protective properties of peptides related functionally and/or
      structurally to vasoactive intestinal peptide (VIP), PC12 cultures were treated
      with iodoacetate as a model for neuronal ischemic/hypoxic injury. Brain tissue
      can be pre-conditioned against lethal ischemia by several mechanisms including
      sub-lethal ischemia, moderate hypoglycemia, heat shock, and growth factors. In
      the present study, a superactive VIP lipophilic analog (Stearyl-Norleucine17-VIP;
      SNV) was used to pre-condition media of PC12 cells. After removal of the
      conditioned media, the cultures were exposed to iodoaceate, which inhibits
      glycolysis. Protective efficacy against iodoacetate-induced injury was assessed
      by the measurements of lactate dehydrogenase (LDH) activity in the media.
      Treatment with iodoacetate for 2.5 h produced a twofold increase in LDH activity
      in the media. The protective effect of SNV had an EC50 of 1 pM. Comparison of the
      preconditioning time required for full protection by SNV showed no apparent
      difference between a 15 min and a 2 h incubation period prior to the addition of
      iodoacetate. Iodoacetate treatment produced a 20% decrease in the RNA transcripts
      encoding activity-dependent neuroprotective protein (ADNP), a novel glia-derived
      protein that is regulated by VIP. The iodoacetate-associated reduction in ADNP
      mRNA was prevented by pre-treatment with SNV. These effects imply that SNV
      provides a regulatory mechanism for ADNP synthesis during glycolytic stress.
      Furthermore, a short exposure to SNV provided potent protection from iodoacetate
      induced toxicity suggesting that SNV may have therapeutic value in the treatment
      of ischemic/hypoxic injury.

PMID- 11303780
TI  - Potassium-induced apoptosis in rat cerebellar granule cells involves cell-cycle
      blockade at the G1/S transition.
AB  - The role of regulators controlling the G1/S transition of the cell cycle was
      analyzed during neuronal apoptosis in post-mitotic cerebellar granule cells in an
      attempt to identify common mechanisms of control with transformed cells. Cyclin
      D1 and its associated kinase activity CDK4 (cyclin-dependent kinase 4) are major
      regulators of the G1/S transition. Whereas cyclin D1 is the regulatory subunit of
      the complex, CDK4 represents the catalytic domain that, once activated, will
      phosphorylate downstream targets such as the retinoblastoma protein, allowing
      cell-cycle progression. Apoptosis was induced in rat cerebellar granule cells by
      depleting potassium in presence of serum. Western-blot analyses were performed
      and protein kinase activities were measured. As apoptosis proceeded, loss in cell
      viability was coincident with a significant increase in cyclin D1 protein levels,
      whereas CDK4 expression remained essentially constant. Synchronized to cyclin D1
      accumulation, cyclin-dependent kinase inhibitor p27Kip1 drastically dropped to
      20% normal values. Cyclin D1/CDK4-dependent kinase activity increased early
      during apoptosis, reaching a maximum at 9-12 h and decreasing to very low levels
      by 48 h. Cyclin E, a major downstream target of cyclin D1, decreased
      concomitantly to the reduction in cyclin D1/CDK4-dependent kinase activity. We
      suggest that neuronal apoptosis takes place through functional alteration of
      proteins involved in the control of the G1/S transition of the cell cycle. Thus,
      apoptosis in post-mitotic neurons could result from a failed attempt to re-enter
      cell cycle in response to extracellular conditions affecting cell viability and
      it could involve mechanisms similar to those that promote proliferation in
      transformed cells.

PMID- 11303781
TI  - Mice overexpressing Bcl-2 in their neurons are resistant to myelin
      oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune
      encephalomyelitis (EAE).
AB  - Multiple sclerosis (MS) is an inflammatory disease of the central nervous system
      (CNS) characterized by destruction of myelin. Recent studies have indicated that
      axonal damage is involved in the pathogenesis of the progressive disability of
      this disease. To study the role of axonal damage in the pathogenesis of MS-like
      disease induced by myelin oligodendrocyte glycoprotein (MOG), we compared
      experimental autoimmune encephalomyelitis (EAE) in wild-type (WT) and transgenic
      mice expressing the human bcl-2 gene exclusively in neurons under the control of
      the neuron-specific enolase (NSE) promoter. Our study shows that, following EAE
      induction with pMOG 35-55, the WT mice developed significant clinical
      manifestations with complete hind-limb paralysis. In contrast, most of the NSE
      bcl-2 mice (16/27) were completely resistant, whereas the others showed only mild
      clinical signs. Histological examination of CNS tissue sections showed multifocal
      areas of perivascular lymphohistiocytic inflammation with loss of myelin and
      axons in the WT mice, whereas only focal inflammation and minimal axonal damage
      were demonstrated in NSE-bcl-2 mice. No difference could be detected in the
      immune potency as indicated by delayed-type hypersensitivity (DTH) and T-cell
      proliferative responses to MOG. We also demonstrated that purified synaptosomes
      from the NSE-bcl-2 mice produce significantly lower level of reactive oxygen
      species (ROS) following exposure to H2O2 and nitric oxide (NO) than WT mice. In
      conclusion, we demonstrated that the expression of the antiapoptotic gene, bcl-2,
      reduces axonal damage and attenuates the severity of MOG-induced EAE. Our results
      emphasize the importance of developing neuroprotective therapies, in addition to
      immune-specific approaches, for treatment of MS.

PMID- 11303782
TI  - Effect of amphetamine on the expression of the metabotropic glutamate receptor 5
      mRNA in developing rat brain.
AB  - Mechanisms underlying the acute effects of amphetamine (AMP) were examined by
      monitoring the expression of metabotropic glutamate receptor 5 (mGluR5) and
      specific 3H-glutamate binding in the developing rat brain. Each of the postnatal
      day (P) 4, P21 and P60 rats received one intraperitoneal injection of AMP, 5
      mg/kg or saline and were sacrificed one hour later. In situ hybridization
      analysis revealed that the AMP treatment raised the levels of the mGluR5 mRNA by
      9-28% in the neurons of the layer 5 of motor and somatosensory cortices, whereas
      reduced the levels by 12-28% in the layer 5 of perirhinal cortex and the
      ventromedial part of caudate-putamen of the 3 ages. In the layer 2/3 neurons of
      cingular cortex, an 18% higher and 14% and 22% lower than control levels of the
      mRNA were detected in the P4 and in the P21 and P60 rats injected with AMP.
      Moreover, the levels of mGluR5 mRNA in the hippocampi and dentate gyri were
      elevated by AMP to 110-151% of controls in the rats of 3 ages. Reversible 3H
      glutamate binding assay showed an increase of 25% and a 12% decrease in the
      binding levels in the cortices of AMP-treated P4 and P21 rats. The AMP
      administration also produced a 27% reduction and 62% elevation in the binding of
      the hippocampi of P4 and P60 rats. The results reveal age- and region-dependent
      changes in the expression of the glutamate receptors induced by AMP and may
      indicate differential plastic capability of the neurons to the drug perturbation.

PMID- 11303783
TI  - Requirement for presenilin 1 in facilitating lagged 2-mediated endoproteolysis
      and signaling of notch 1.
AB  - Presenilin 1 (PS1), a polytopic membrane protein, is required for endoproteolytic
      processing at gamma-secretase site within the transmembrane domain of amyloid
      precursor proteins (APP). In addition, PS1 and its orthologues facilitate
      signaling of Notch family members, cell-surface receptors that specify cell fates
      during development. To clarify the mechanism(s) by which PS facilitates Notch
      signaling, we examined human Jagged-2-dependent metabolism and activity of a
      chimeric full-length Notchl-GFP molecule expressed in fibroblasts with
      heterozygous, or homozygous deletions of PS1. We demonstrate that PS1 is required
      for facilitating Jagged 2-mediated proteolysis and that translocation and
      accumulation of NICD in the nucleus correlates with signaling activity. Moreover,
      in a ligand-independent, Ca2+-depletion paradigm, we demonstrate that PS1
      facilitates endoproteolysis of a plasma-membrane-associated, Notch1-GFP
      derivative. Finally, we report that NICD production is inhibited by L-685,458, a
      potent and selective inhibitor that blocks solubilized gamma-secretase activity
      and Abeta production in cultured cells. These findings strongly suggest that
      intramembranous processing of APP and Notch 1 are mediated by similar, if not
      identical, proteases that require PS1 for their activation.

PMID- 11303784
TI  - Expression patterns of mouse repressor element-1 silencing transcription factor 4
      (REST4) and its possible function in neuroblastoma.
AB  - The expression pattern of the repressor element-1 silencing transcription factor
      (REST) also known as the neuron-restrictive silencer factor (NRSF) and its
      truncated forms have been analyzed in the neuroblastoma cell lines, NS20Y and
      NIE115 and in NIH3T3 cells. The neuroblastoma cell lines express transcripts of
      REST/NRSF and its neuron-specific truncated form REST4; with REST4 being the
      major transcript. NIH3T3 cells express predominantly REST/NRSF, with no
      detectable REST4. The cellular localization of REST4, determined using a REST4
      GFP fusion protein, was shown to be nuclear. Mutational analysis implicates the
      zinc finger domains as the nuclear-targeting signal. Analysis of reporter-gene
      activities in the NS20Y cell line showed that the presence of four RE-1/NRSE
      sequences did not affect promoter activity. However, coexpression of exogenous
      REST4 produces a small increase in promoter activity of the reporter plasmid,
      whereas expression of exogenous REST/NRSF leads to repression. In the NIH3T3 cell
      line, the RE-1/NRSE sequence leads to repression of reporter-gene activity,
      whereas introduction of exogenous REST4 leads to de-repression. These data
      indicate that REST4 does not act as a transcriptional repressor. However, they
      support a mechanism where REST4 can block the repressor activity of REST/NRSF.

PMID- 11303786
TI  - The ortholog of human ataxin-2 is essential for early embryonic patterning in C.
      elegans.
AB  - Ataxin-2, the gene product of the human spinocerebellar ataxia type 2 (SCA2)
      gene, is a protein of unknown function. Ataxin-2 interacts with ataxin-2-binding
      protein 1 (A2BP1), a member of a novel family of putative RNA-binding proteins.
      Because the sequences of ataxin-2 and A2BP1 are evolutionarily conserved, we
      investigated functional aspects and expression pattern in the nematode
      Caenorhabditis elegans. Human ataxin-2 has 20.1% amino acid identity and 43.9%
      similarity to its C. elegans ortholog, designated ATX-2, that encodes a predicted
      1026 aa protein. One of the worm orthologs of human A2BP1 is the numerator
      element FOX-1, with an overall 29.8% aa identity. We studied the expression
      pattern of atx-2 using the endogenous promotor coupled with a GFP expression
      vector. Atx-2 was widely expressed in the adult worm with strong expression in
      muscle and nervous tissue. It was also heavily expressed in the embryo. In order
      to elucidate the function of atx-2 and fox-1, we conducted RNA interference
      (RNAi) studies. The interfering dsRNA was introduced into larval L4 stage worms
      of the N2 strain by microinjection or soaking. DsRNA representing the full-length
      atx-2 gene resulted in arrested embryonic development in the offspring of all 58
      microinjected worms. Nomarski imaging showed embryos in different stages of
      developmental arrest, indicating an essential role of atx-2 for early embryonic
      development. When fox-1 was targeted by RNAi, there was a marked reduction in the
      number of eggs per worm. The results presented here underline previous findings
      about the interaction of human ataxin-2 and A2BP1.

PMID- 11303785
TI  - Neurotrophin dependence domain: a domain required for the mediation of apoptosis
      by the p75 neurotrophin receptor.
AB  - The mechanisms underlying neurotrophin dependence, and cellular dependent states
      in general, are unknown. We show that a 29 amino acid region in the intracellular
      domain of the common neurotrophin receptor, p75NTR, is required for the mediation
      of apoptosis by p75NTR. Furthermore, contrary to results obtained with Fas,
      monomeric p75NTR is required for apoptosis induction, whereas multimerization
      inhibits the pro-apoptotic effect. Within the 29-residue domain required for
      apoptosis induction by p75NTR, a 14-residue region is sufficient as a peptide
      inducer of apoptosis. This 14-residue peptide requires the positively charged
      carboxyterminal residues for its effect on cell death, and these same residues
      are required by the full-length p75NTR. These studies define a novel type of
      domain that mediates neurotrophin dependence, and suggest that other cellular
      dependent states may be mediated by proteins displaying similar domains.

PMID- 11303787
TI  - Inhibition of caspase-3 activation by SB 203580, p38 mitogen-activated protein
      kinase inhibitor in nitric oxide-induced apoptosis of PC-12 cells.
AB  - Mitogen-activated protein kinase (MAPK) p38 plays pivotal role in cell
      proliferation, differentiation, and apoptosis when cysteine protease caspase
      induces apoptosis in different cell systems. SB 203580 (4-(4-fluorophenyl)-2-(4
      methylsulfinylphenyl)-5-(4-pyridyl)1 H-imidazole) is widely used as a specific
      inhibitor of p38 MAPK, and prevents apoptosis induced by various agents. The
      effect of SB 203580 on nitric oxide(NO)- or peroxynitrite-induced cell death is
      not known. Western blotting results indicate that p38 MAPK was activated
      significantly in NO- or peroxynitrite-induced cell death in a time-dependent
      manner, and subsequently this cell death was markedly inhibited by SB 203580, as
      determined by fluorescence-activated cell sorting (FACS)-can analyzer.
      Furthermore, NO/peroxynitrite-induced caspase-3 activation was notably inhibited
      by SB 203580, however, phosphorylation of either p38 MAPK or p44/42 was not
      influenced by SB 203580. Thus, it is likely that SB 203580 prevents
      NO/peroxynitrite-induced cell death by inhibiting caspase-3 activation in PC-12
      cells.

PMID- 11303788
TI  - Caprine mucopolysaccharidosis IIID: a preliminary trial of enzyme replacement
      therapy.
AB  - Mucopolysaccharidosis type IIID (MPS IIID) is a lysosomal storage disorder
      resulting from lack of activity of the lysosomal hydrolase N-acetylglucosamine 6
      sulfatase (6S) (EC 3.1.6.14). The syndrome is associated with systemic and
      central nervous system (CNS) heparan sulfate glycosaminoglycan (HS-GAG)
      accumulation, secondary storage of lipids, and severe, progressive dementia. In
      this investigation, caprine MPS IIID, established as a large animal model for the
      human disease, was used to evaluate the efficacy of enzyme replacement therapy
      (ERT). Recombinant caprine 6S (rc6S) (1 mg/kg/dose) was administered
      intravenously to one MPS IIID goat kid at 2, 3, and 4 wks of age. Five days after
      the last dose, the uronic acid (UA) content and the composition of uncatabolized
      HS-GAG fractions in the brain of the ERT-treated MPS IIID kid were similar to
      those from a control, untreated MPS IIID animal. However, hepatic uronic acid
      levels in the treated MPS IIID kid were approximately 90% lower than those in the
      untreated MPS IIID control; whereas the composition of the residual hepatic HS
      GAG was identical to that in the untreated animal. Marked reduction of lysosomal
      storage vacuoles in hepatic cells of the treated MPS IIID kid was observed, but
      ERT had no effect on CNS lesions. No residual 6S activity was detected in brain
      or liver. This preliminary investigation indicates that other treatment regimens
      will be necessary to ameliorate MPS III-related CNS lesions.

PMID- 11303789
TI  - Low frequency of chromosomal imbalances in anaplastic ependymomas as detected by
      comparative genomic hybridization.
AB  - We screened 26 ependymomas in 22 patients (7 WHO grade I, myxopapillary, myE; 6
      WHO grade II, E; 13 WHO grade III, anaplastic, aE) using comparative genomic
      hybridization (CGH) and fluorescence in situ hybridization (FISH). 25 out of 26
      tumors showed chromosomal imbalances on CGH analysis. The chromosomal region most
      frequently affected by losses of genomic material clustered on 13q (9/26). 6/7
      myE showed a loss on 13q14-q31. Other chromosomes affected by genomic losses were
      6q (5/26), 4q (5/26), 10 (5/26), and 2q (4/26). The most consistent chromosomal
      abnormality in ependymomas so far reported, is monosomy 22 or structural
      abnormality 22q, identified in approximately one third of Giemsa-banded cases
      with abnormal karyotypes. Using FISH, loss or monosomy 22q was detected in small
      subpopulations of tumor cells in 36% of cases. The most frequent gains involved
      chromosome arms 17 (8/26), 9q (7/26), 20q (7/26), and 22q (6/26). Gains on 1q
      were found exclusively in pediatric ependymomas (5/10). Using FISH, MYCN proto
      oncogene DNA amplifications mapped to 2p23-p24 were found in 2 spinal ependymomas
      of adults. On average, myE demonstrated 9.14, E 5.33, and aE 1.77 gains and/or
      losses on different chromosomes per tumor using CGH. Thus, and quite
      paradoxically, in ependymomas, a high frequency of imbalanced chromosomal regions
      as revealed by CGH does not indicate a high WHO grade of the tumor but is more
      frequent in grade I tumors.

PMID- 11303790
TI  - Phosphorylated map kinase (ERK1, ERK2) expression is associated with early tau
      deposition in neurones and glial cells, but not with increased nuclear DNA
      vulnerability and cell death, in Alzheimer disease, Pick's disease, progressive
      supranuclear palsy and corticobasal degeneration.
AB  - Abnormal tau phosphorylation and deposition in neurones and glial cells is one of
      the major features in taupathies. The present study examines the involvement of
      the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's
      disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration
      (CBD), by Western blotting, single and double-labelling immunohistochemistry, and
      p21Ras activation assay. Since this pathway is also activated in several
      paradigms of cell death and cell survival, activated ERK expression is also
      analysed with double-labelling immunohistochemistry and in situ end-labelling of
      nuclear DNA fragmentation to visualise activated ERK in cells with increased
      nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that
      identifies phosphorylation-independent MEK1, whose expression levels are not
      modified in diseased brains. The ERK antibody recognises one band of 42 kD
      corresponding to the molecular weight of phosphorylation-independent ERK2; the
      expression levels, as well as the immunoreactivity of ERK in individual cells, is
      not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands
      of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression
      levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and
      CBD. Moreover, immunohistochemistry discloses granular precipitates in the
      cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting
      early tau deposition, whereas neurones with developed neurofibrillary tangles are
      less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in
      PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic
      neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large
      numbers of tau-positive glial cells in PSP and CBD, as seen with double-labelling
      immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK
      immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD.
      Finally, activated Ras expression levels are increased in AD cases when compared
      with controls. These results demonstrate increased phosphorylated (active) ERK
      expression in association with early tau deposition in neurones and glial cells
      in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK
      pathway of tau phosphorylation in AD.

PMID- 11303791
TI  - p14ARF deletion and methylation in genetic pathways to glioblastomas.
AB  - The CDKN2A locus on chromosome 9p21 contains the p14ARF and p16INK4a genes, and
      is frequently deleted in human neoplasms, including brain tumors. In this study,
      we screened 34 primary (de novo) glioblastomas and 16 secondary glioblastomas
      that had progressed from low-grade diffuse astrocytomas for alterations of the
      p14ARF and p16INK4a genes, including homozygous deletion by differential PCR,
      promoter hypermethylation by methylation-specific PCR, and protein expression by
      immunohistochemistry. A total of 29 glioblastomas (58%) had a p14ARF homozygous
      deletion or methylation, and 17 (34%) showed p16INK4a homozygous deletion or
      methylation. Thirteen glioblastomas showed both p14ARF and p16INK4a homozygous
      deletion, while nine showed only a p14ARF deletion. Immunohistochemistry revealed
      loss of p14ARF expression in the majority of glioblastomas (38/50, 76%), and this
      correlated with the gene status, i.e. homozygous deletion or promoter
      hypermethylation. There was no significant difference in the overall frequency of
      p14ARF and p16INK4a alterations between primary and secondary glioblastomas. The
      analysis of multiple biopsies from the same patients revealed hypermethylation of
      p14ARF (5/15 cases) and p16INK4a (1/15 cases) already at the stage of low-grade
      diffuse astrocytoma but consistent absence of homozygous deletions. These results
      suggest that aberrant p14ARF expression due to homozygous deletion or promoter
      hypermethylation is associated with the evolution of both primary and secondary
      glioblastomas, and that p14ARF promoter methylation is an early event in subset
      of astrocytomas that undergo malignant progression to secondary glioblastoma.

PMID- 11303792
TI  - Expression of synaptopodin, an actin-associated protein, in the rat hippocampus
      after limbic epilepsy.
AB  - Synaptopodin, a 100 kD protein, associated with the actin cytoskeleton of the
      postsynaptic density and dendritic spines, is thought to play a role in
      modulating actin-based shape and motility of dendritic spines during formation or
      elimination of synaptic contacts. Temporal lobe epilepsy in humans and in rats
      shows neuronal damage, aberrant sprouting of hippocampal mossy fibers and
      subsequent synaptic remodeling processes. Using kainic acid (KA) induced epilepsy
      in rats, the postictal hippocampal expression of synaptopodin was analyzed by in
      situ hybridization (ISH) and immunohistochemistry. Sprouting of mossy fibers was
      visualized by a modified Timm's staining. ISH showed elevated levels of
      Synaptopodin mRNA in perikarya of CA3 principal neurons, dentate granule cells
      and in surviving hilar neurons these levels persisted up to 8 weeks after seizure
      induction. Synaptopodin immunoreactivity in the dendritic layers of CA3, in the
      hilus and in the inner molecular layer of the dentate gyrus (DG) was initially
      reduced. Eight weeks after KA treatment Synaptopodin protein expression returned
      to control levels in dendritic layers of CA3 and in the entire molecular layer of
      the DG. The recovery of protein expression was accompanied by simultaneous supra-
      and infragranular mossy fiber sprouting. Postictal upregulation of Synaptopodin
      mRNA levels in target cell populations of limbic epilepsy-elicited damage and
      subsequent Synaptopodin protein expression largely co-localized with remodeling
      processes as demonstrated by mossy fiber sprouting. It may thus represent a novel
      postsynaptic molecular correlate of hippocampal neuroplasticity.

PMID- 11303794
TI  - Introduction: recent advances in hereditary neuromuscular diseases of childhood.

PMID- 11303795
TI  - Non-sarcolemmal muscular dystrophies.
AB  - The muscular dystrophies are characterised by progressive muscle weakness and
      wasting. Pathologically the hallmarks are muscle fibre degeneration and fibrosis.
      Several recessive forms of muscular dystrophy are caused by defects in proteins
      localised to the sarcolemma. However, it is now apparent that others are due to
      defects in a wide range of proteins including those which are either nuclear
      related (Emery-Dreifuss type muscular dystrophies, oculopharyngeal muscular
      dystrophy), enzymatic (limb-girdle muscular dystrophy 2A, myotonic dystrophy) or
      sarcomeric (limb-girdle muscular dystrophies 1A and 2G). Although the clinical
      and molecular basis of these disorders is heterogeneous all display myopathic
      morphological features. These include variation in fibre size, an increase in
      internal nuclei, and some myofibrillar distortion. Degeneration and fibrosis
      occur, but usually not to the same extent as in muscular dystrophies associated
      with sarcolemmal protein defects. This review outlines the genetic basis of these
      "non-sarcolemmal" forms of dystrophy and discusses current ideas on their
      pathogenesis.

PMID- 11303793
TI  - Increased expression of the normal cellular isoform of prion protein in inclusion
      body myositis, inflammatory myopathies and denervation atrophy.
AB  - The cellular isoform of the prion protein (PrPc) is a
      glycosylphosphatidylinositol-anchored glycoprotein, normally expressed in neural
      and non-neural tissues, including skeletal muscle. In transmissible spongiform
      encephalopathies, or prion diseases, PrPc, which is soluble in nondenaturing
      detergent and sensitive to proteinase K (PK)-treatment, represents the molecular
      substrate for the production of a detergent-insoluble and PK-resistant isoform,
      termed PrP(Sc). In human prion diseases, PrP(Sc) accumulation occurs only in
      brain tissues, with the exception of new variant Creutzfeldt-Jakob disease, where
      PrP(Sc) is also detected in lymphoid tissues. Increased amounts of prion protein
      expression and deposition have been described in pathological muscle fibers of
      two human muscle disorders, called sporadic inclusion-body myositis (s-IBM) and
      hereditary inclusion-body myopathy, but it is unknown whether accumulated prion
      protein reflects normal PrPc or PrP(Sc). We investigated the biochemical
      characteristics of prion protein in normal human muscle, s-IBM, other
      inflammatory myopathies and denervation atrophy. We report that 1) both the
      glycoform profile and size of the normal muscle PrPc are different from those of
      human brain PrPc; 2) in addition to s-IBM, increased PrPc expression is seen in
      polymyositis, dermatomyositis and neurogenic muscle atrophy, but PrPc glycoforms
      are unchanged; 3) only the normal PrPc isoform, and not PrP(Sc), is detected in s
      IBM. The present results exclude that s-IBM is a prion disease.

PMID- 11303796
TI  - Congenital myopathies.
AB  - Most congenital myopathies have been defined on account of the morphological
      findings in enzyme histochemical preparations. In effect, the diagnosis of this
      group of diseases continues to be made on the histological pattern of muscle
      biopsies. However, progress has been made in elucidating the molecular genetic
      background of several of the congenital myopathies. In this updated review we
      address those congenital myopathies for which gene defects and mutant proteins
      have been found (central core disease, nemaline myopathies, desminopathy,
      actinopathy, certain vacuolar myopathies, and myotubular myopathy) and the other
      disease with central nuclei (centronuclear myopathy).

PMID- 11303797
TI  - Sarcolemmopathy: muscular dystrophies with cell membrane defects.
AB  - In this article, we review the molecular pathology of muscular dystrophies caused
      by defects of proteins located within or near cell membranes. These disorders
      include Bethlem myopathy, merosinopathy, dystrophinopathy, sarcoglycanopathies,
      integrinopathy, dysferlinopathy and caveolinopathy. We refer to these diseases
      collectively as sarcolemmopathy. Here, we describe the biological functions of
      these proteins in the context of muscular contractions and their roles in the
      infrastructure of muscle; defects of muscle infrastructures cause those diseases.
      As an example, in dystrophinopathy, cell membranes have mechanical defects due to
      the absence of dystrophin. Cracks of the cell membrane induced by muscle
      contraction may allow the influx and efflux of substances that trigger muscle
      cell degeneration. However, such cracks may be resealed on relaxation. In
      addition, dystrophinopathy causes secondary defects of various dystrophin
      associated proteins suggesting that defects in cell signaling participate in the
      pathologic process. With regard to other sarcolemmopathies, we discuss
      pathological mechanisms based on available data.

PMID- 11303798
TI  - Spinal muscular atrophy: present state.
AB  - Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease caused by
      homozygous deletions or mutations in the SMN1 gene on Chr.5q13. SMA spans from
      severe Werdnig-Hoffmann disease (SMA 1) to relatively benign Kugelberg-Welander
      disease (SMA 3). Onset before birth possibly aggravates the clinical course,
      because immature motoneurons do not show compensatory sprouting and collateral
      reinnervation, and motor units in SMA 1, in contrast to those in SMA 3, are not
      enlarged. Genetic evidence indicates that SMN2, a gene 99% identical to SMN1, can
      attenuate SMA severity: in patients, more SMN2 copies and higher SMN protein
      levels are correlated with milder SMA. There is evidence that SMN plays a role in
      motoneuron RNA metabolism, but it has also been linked to apoptosis. Several
      mouse models with motoneuron disease have been successfully treated with
      neurotrophic factors. None of these models is, however, homologous to SMA.
      Recently, genetic mouse models of SMA have been created by introducing human SMN2
      transgenes into Smn knockout mice or by targeting the Smn gene knockout to
      neurons. These mice not only provide important insights into the pathogenesis of
      SMA but are also crucial for testing new therapeutic strategies. These include
      SMN gene transfer, molecules capable to up-regulate SMN expression and trophic or
      antiapoptotic factors.

PMID- 11303799
TI  - XlVth International Congress of Neuropathology, 3-6 September, 2000, Birmingham,
      United Kingdom.

PMID- 11303800
TI  - The 8th International Congress on Neuronal Ceroid Lipofuscinoses (Batten disease)
      -NCL 2000, 20-24 September, 2000, Oxford, United Kingdom.

PMID- 11303801
TI  - October 2000: a 47 year old man with long-standing progressive tetraparesis.
AB  - A 47-year-old man with a six-month history of progressive tetraparesis and
      sphincter disturbances developed tetraplegy after two years and died. A cervical
      MRI revealed an ill-defined, enhancing lesion from C1 to C6, internally attached
      to the dura mater and compressing the spinal cord. At necropsy, eight whitish
      nodes and diffuse thickening of the dura mater from C1 to C6 were found.
      Histological studies revealed multiple en plaque lymphoplasmacyte-rich
      meningiomas. The radiologic and pathologic aspects of lymphoplasmacyte-rich
      meningioma are reviewed and the atypical features of this case, such as
      macroscopic appearance and the histological variant, are described.

PMID- 11303802
TI  - November 2000: 13 year old girl with back pain and leg weakness.
AB  - A 13 year-old girl presented with back pain and recurrent falls of one year, with
      more recent loss of ambulation and bladder control. Examination showed spasticity
      and a sensory level bilaterally at T8. CT and MRI scans showed an epidural soft
      tissue mass with spinal cord compression and destruction of the pedicle,
      transverse process and other portions of a mid-thoracic vertebral body.
      Histologic examination of the gross total resection showed a pigmented
      villonodular synovitis (PVNS). PVNS is most common in the knee and only 26 cases
      have been reported in the spine. Although vertebral bodies are rarely involved,
      it is important to include PVNS in the differential diagnosis of spinal lesions
      because of its tendency to recur locally if not totally resected.

PMID- 11303803
TI  - December 2000: 6 month old boy with 2 week history of progressive lethargy.
AB  - This 6-month-old Caucasian boy presented with a 10-day history of lethargy,
      obtundation, inability to hold his head up and mild torticollis. MRI and CT scans
      showed a large solid and cystic mass involving the right temporal, parietal and
      occipital lobes, pineal, superior pons, mesencephalon and posterior right
      thalamus. He underwent craniotomy initially for a partial tumor resection with an
      intraoperative diagnosis of desmoplastic astrocytoma. With immunohistochemistry
      and special stains the diagnosis of desmoplastic infantile ganglioglioma (DIG)
      was made. A near total resection was performed a week after initial resection.The
      patient then was treated with chemotherapy. Two months later an MRI showed tumor
      growth. Following additional aggressive chemotherapy, an MRI at 5 months post
      resection indicated further tumor progression. This case illustrates that some
      DIGs may behave more aggressively than typical WHO grade I lesions.

PMID- 11303804
TI  - An update on Helicobacter pylori microbiology and infection for the new
      millennium.
AB  - The finding of the bacterium Helicobacter pylori in patients with symptomatic
      gastric diseases was a breakthrough for both treatment of peptic ulcer disease
      and studies of other infectious diseases. Helicobacter pylori infection is rare
      among the young, indicating that improved childhood living conditions have halted
      the transmission of the bacterium within families, with a parallel decrease in
      symptomatic gastroduodenal diseases. Extensive strain variation in H. pylori has
      been demonstrated at both the genomic and the protein level, and the interstrain
      variation is higher than in any other bacterium studied so far. Pathogenic
      markers in H. pylori and host genetics are both of importance for disease
      outcome. Genotypic or phenotypic markers of H. pylori strains may be used to
      discriminate patients who should undergo eradication therapy from those who might
      not benefit from it. Possible positive effects of the infection are still under
      investigation, and several hypotheses regarding the etiology of diseases in
      different parts of the stomach have been proposed. To be able to separate the
      disease-causing infections from the silent infections is a real challenge for the
      new millennium, and one of the most important issues for therapy and prevention,
      in the research field of H. pylori.

PMID- 11303805
TI  - Determinants of vaccine-induced resistance in animal models of pulmonary
      tuberculosis.
AB  - A more effective vaccine will be essential if the global tuberculosis (TB)
      pandemic is ever to be controlled. A large number of new tuberculosis vaccines
      have been developed, representing the whole range of modern strategies for
      vaccine formulation and delivery. There is currently no alternative to testing
      these new vaccines in experimental animals challenged with virulent
      Mycobacteriurn tuberculosis in order to assess their protective efficacy.
      Although such testing is being carried out in several animal species (mice,
      guinea pigs, rabbits), all rational models include pulmonary challenge with a low
      dose of virulent mycobacteria. The quantitative measures for TB vaccines include
      increased survival, amelioration of clinical signs and symptoms (e.g. prevention
      of weight loss), decreased lesion size, reduction in bacillary loads in the
      lungs, and prevention of extrapulmonary dissemination and hematogenous reseeding
      of the lung. Although the ultimate objective of vaccination in humans is to
      prevent transmission to susceptible contacts, no such measurement is being used
      in animal studies of new vaccines. The validation of an immunological "correlate
      of protection" is urgently needed. Candidates for such a correlate include
      antigen-specific interferon-gamma production by T cells of the memory phenotype
      (CD45RB(high) or mycobacterial killing by macrophages co-cultured with immune T
      cells. Additional animal models must be developed for vaccines designed to
      prevent endogenous reactivation or exogenous reinfection, or to be used as a
      adjunct to chemotherapy.

PMID- 11303806
TI  - Clinical characteristics of Group G streptococcal bacteremia in Taiwan.
AB  - The results of this retrospective study showed that Group G streptococcal
      bacteremia was an acute febrile disease with low mortality. Most patients were >
      60 y old but there was a strong association between age < 60 y and malignancy.
      Cases clustered in summer and the most common port of entry was the skin.

PMID- 11303807
TI  - Ampicillin-resistant enterococci in a Swedish university hospital: nosocomial
      spread and risk factors for infection.
AB  - Ampicillin-resistant enterococci (ARE) have recently emerged as clinical
      pathogens in Sweden. Between 1991 and 1995 the incidence of ARE among
      enterococcal isolates at Uppsala University Hospital increased from 0.5% to 8.1%.
      Shedding of ARE from infected cases and risk factors for infection with ARE were
      studied during a period of 7 months for 38 ARE cases and 38 controls with
      ampicillin-susceptible enterococci. ARE cases had longer mean duration of
      hospitalization than controls (29 d vs. 15 d; p = 0.002). In univariate analysis
      other risk factors for infection with ARE were found to be prior therapy with > 2
      antimicrobials (odds ratio [OR] 3.3; 95% confidence interval [CI] 1.2-9.5), > 4
      weeks of antimicrobial therapy (OR 6.9; CI 1.8-28.3) and cephalosporin therapy
      (OR 9.1; CI 2.6-33.7). Fourteen of 26 skin carriers of ARE were found to be
      shedding ARE to the environment, compared to 2 of 12 non-skin carriers (p =
      0.03). Pulsed-field gel electrophoresis suggested multifocal origin of the
      majority of the infecting ARE strains. Non-recognized fecal colonization and
      silent spread of ARE among many patients and over a prolonged time period is
      suggested to be the main explanation for the increase of ARE infections in our
      hospital. Infection control measures focusing on protecting patients at high risk
      for ARE infections and further efforts to optimize antimicrobial use are
      proposed.

PMID- 11303808
TI  - Clinical significance and impact on mortality of extended-spectrum beta lactamase
      producing Enterobacteriaceae isolates in nosocomial bacteremia.
AB  - During an 8-month period, 55 episodes of nosocomial bacteremia caused by
      Enterobacteriaceae species were identified in a tertiary medical center, of which
      26 (47%) were caused by extended-spectrum beta lactamase (ESBL)-producing
      organisms. ESBL production was associated with resistance to aminoglycosides,
      fluoroquinolones, tetracycline and co-trimoxazole compared with non-ESBL
      producing organisms (p < 0.01). By multivariate analysis, infection with ESBL
      producing organisms was associated with previous antibiotic therapy and central
      venous catheter insertion and mortality was associated with heart failure,
      malignancy and a prolonged hospital stay. Nineteen (73%) patients infected with
      ESBL-producing organisms received adequate empirical antibiotic therapy and all
      26 received adequate definitive therapy. The in-hospital mortality rate did not
      differ between patients infected with ESBL producers and those infected by non
      ESBL-producing Enterobacteriaceae species [13/26 (50%) and 11/29 (38%),
      respectively] (p > 0.5).

PMID- 11303809
TI  - Community spread of Legionella pneumophila serogroup 1 in temporal relation to a
      nosocomial outbreak.
AB  - To clarify whether a nosocomial outbreak of legionnaires' disease in the Varnamo
      hospital in Sweden was part of a wider outbreak in the Varnamo community a number
      of investigations were performed. First, the proportion of cases of legionnaires'
      disease in a group with nosocomially acquired pneumonia (11%) was compared to the
      proportion within a group with community-acquired pneumonia (14%) and the
      difference was found not to be significant (p > 0.05). Second, the proportion of
      the nursing staff at the Varnamo hospital with an elevated antibody titre (> or =
      16) to Legionella pneumophila serogroup (sg) 1 (33%, 84/258) was compared to the
      proportion in a group of local residents of Varnamo community (26%, 25/96) and
      found not to be significant; in contrast, comparison with the proportion in a
      group from the assistant nursing staff at another hospital 60 km away (5%, 4/80)
      was highly significant (p < 0.001). Furthermore, Legionella species were cultured
      from samples drawn from the hospital water supply as well from the water supply
      from municipal buildings. In 1996 a follow-up study was conducted, which showed
      that < 1% of the assistant nurses and local residents had an elevated titre to L.
      pneumophila sg 1. These results indicate that there was a temporary spread of L.
      pneumophila sg 1 in the Varnamo community at the beginning of 1991, both in the
      local hospital and the surrounding community. This implies that physicians should
      be aware of community-acquired cases of legionnaires' disease when a nosocomial
      outbreak is detected.

PMID- 11303810
TI  - Limited diagnostic usefulness of antibodies to cytoplasmic proteins of Brucella
      in early-treated human brucellosis.
AB  - Antibodies to cytoplasmic proteins (CP) of Brucella have been shown to be useful
      for the diagnosis of human brucellosis; however, some early-diagnosed patients
      lack such an antibody response while having high titers of antibodies to
      lipopolysaccharide (LPS). To address which factors determine this serological
      discrepancy in the early stages of brucellosis we examined the antibody response
      to CP and LPS of 21 patients involved in an outbreak of B. melitensis infection
      who had a short duration of clinical illness at diagnosis (3-40 d). At diagnosis,
      antibodies to LPS (IgM and/or IgG) were found in all patients, while anti-CP
      antibodies were detected in 16 subjects (76%). At 6 weeks post-diagnosis IgG to
      CP (with or without IgM) had been detected in 13 patients and IgM alone had been
      found in 4; however, 4 other patients (19%) had no response to CP. No significant
      differences were found between these 3 groups in terms of age, gender,
      antimicrobial agents or factors that could hamper the immune response. Notably,
      however, the 4 non-responders and 3 of the 4 patients having only IgM to CP had
      started antibiotic therapy within 14 d post-symptoms, while treatment was started
      later in 9 of 13 patients who developed anti-CP IgG. In addition, maximum titers
      of IgG to CP tended to be lower in early-treated patients. These results suggest
      that very early antibiotic therapy hampers the antibody response to Brucella CP
      but has little impact on the anti-LPS response. Given the higher specificity of
      the former and the higher sensitivity of the latter, both reactivities should be
      measured in order to diagnose human brucellosis.

PMID- 11303811
TI  - Seroprevalence of human granulocytic ehrlichiosis in high-risk groups in Denmark.
AB  - The aim of this study was to evaluate the seroprevalence of human granulocytic
      ehrlichiosis (HGE) among 300 residents in the county of Funen, Denmark. All of
      these people had either suspected or confirmed borreliosis. Two hundred control
      sera were included in the study. Samples were submitted by general practitioners
      and by hospital departments. An indirect immunofluorescence assay was used to
      identify sera reactive to HGE and an enzyme-linked immunosorbent assay was used
      to analyse Borrelia burgdorferi antibodies. There were 63 (21%) HGE-positive
      sera, 53 of which came from Borrelia-seropositive patients. Among patients with
      negative Borrelia serology, but with clinical suspicion of borreliosis, 14.3%
      were HGE-positive (n = 70). Of the 200 control sera, 3.5% were HGE-positive and
      10.5% were Borrelia-positive. No HGE-positive samples were found among subjects <
      20 y of age, wheras 20.4% of Borrelia seropositive samples where from subjects <
      20 y of age. No mortality was observed in the HGE-positive group and the
      percentage of serum samples positive for both Borrelia and HGE did not differ
      significantly between hospitalized and non-hospitalized patients. Our study
      indicates that HGE infection with or without concomitant or previous Borrelia
      burgdorferi infection is common in tick-exposed individuals > 20 y old in the
      county of Funen, Denmark.

PMID- 11303812
TI  - Pulmonary imaging and function in the common cold.
AB  - The common cold is generally considered to be an upper respiratory tract
      infection. We studied the lower respiratory tract in 76 otherwise healthy young
      adults with the common cold. Viral infection was diagnosed in 56 (74%) of the 76
      subjects. Rhinovirus was detected in 42 (55%) subjects. Chest radiography (CR)
      and high-resolution computerized tomography (HRCT) were carried out in 40
      subjects on day 7, and pulmonary function testing with bronchodilator challenge
      was carried out in 36 patients on days 7 and 21 of the study. Clinical
      examinations were carried out on days 1, 7 and 21. The subjects recorded their
      symptoms on a diary card for 20 d. The mean duration of cough was 8.4 (SD 6.5) d
      and that of sputum production 5.9 (SD 6.4) d. No abnormal findings were detected
      in the lungs on auscultation. CR and HRCT showed no pulmonary changes associated
      with the common cold. No clinically remarkable increases were seen in peak
      expiratory flow, forced expiration volume in 1 s or forced vital capacity after
      bronchodilator challenge on either days 7 or 21. All patients made a clinical
      recovery without antimicrobial therapy within 21 d. We conclude that the common
      cold in young otherwise healthy adults is an upper respiratory tract infection
      and that clinically important abnormalities in the lower respiratory tract are
      rare.

PMID- 11303813
TI  - Low sensitivity of serum procalcitonin in bacterial meningitis in adults.
AB  - Several studies have suggested high predictive values of serum procalcitonin
      (PCT) for the discrimination of bacterial and viral meningitis in children and
      adults. Here, we report PCT serum concentrations in 12 adults suffering from
      bacterial meningitis. PCT on admission was normal ( < or = 500 pg/ml) in 3 and
      between 500 and 1,000 pg/ml in 2 patients without evidence of concurrent
      bacterial infections. Conversely, in 5 patients with PCT concentrations between
      2,268 and 38,246 pg/ml other infections were present. PCT concentrations were
      higher with typical meningitis agents (pneumococci and meningococci 12,679 +/-
      13,092 pg/ml vs. other bacteria 4048 +/- 9187 pg/ml, p = 0.041) whilst in
      nosocomial bacterial meningitis after neurosurgery (n = 3) serum PCT remained
      normal. We believe that PCT is of limited diagnostic value in adults suffering
      from bacterial meningitis, especially in cases due to unusual agents or of
      nosocomial origin. Elevated PCT in bacterial meningitis may indicate the presence
      of bacterial inflammation outside the central nervous system.

PMID- 11303814
TI  - Influence of an infectious disease consulting service on quality and costs of
      antibiotic prescriptions in a university hospital.
AB  - An infectious disease consulting service was set up at a large tertiary
      university hospital in 1996 to evaluate and to improve antibiotic prescription
      patterns. Treatment guidelines for the most common bacterial infections were
      implemented. On daily ward rounds antibiotic therapies without evidence of an
      infectious disease were stopped and inappropriate regimens were changed by an
      infectious disease specialist. During a 6-month prospective intervention period,
      3,528 patients were studied on 13 wards of the department of internal medicine;
      513 of these patients (14.5%) received antibiotic therapy. These treatment
      courses were evaluated as adequate in 394 cases (76.8%) and incorrect in 119
      cases (23.2%). Inadequate antibiotic substances were chosen in 72 out of 119
      cases (60.5%) and there was no indication for treatment in 38 out of 119 cases
      (32%). Pathogen-specific therapies were inadequate significantly more often than
      empirical antimicrobial therapies (p < 0.001). In addition, the duration of the
      perioperative prophylaxis could be limited to 1 d. Comparing the intervention
      period with a 3-month control interval without an infectious disease consulting
      service, a total of 31,510 Euro (including the costs for the infectious disease
      specialist) could be saved. No increase in infection-related mortality or length
      of stay was observed. These data show that an infectious disease consulting
      service optimizes antibiotic usage, and is cost-effective as a result of a
      significant cost reduction in hospitals, while not interfering with the quality
      of medical care.

PMID- 11303815
TI  - Pharmacokinetics of ceftazidime in febrile neutropenic patients.
AB  - Eight patients with fever and neutropenia were given 2 g of ceftazidime i.v. as a
      bolus injection over the course of 3 min. The pharmacokinetic variables for
      ceftazidime were similar to those found previously in febrile, acutely ill, non
      neutropenic patients. The area under the plasma-concentration-time curve was
      significantly smaller, and the terminal half-life (t1/2lambda(z)) significantly
      shorter, compared with elderly, healthy subjects (p < 0.005). Three patients
      survived long enough to be assayed after normalization of temperature and
      neutrophil counts. Glomerular filtration rates and clearances tended to be higher
      and the area under the curve and half-life lower on the day of fever and
      neutropenia. When considering our data in relation to known MIC values for common
      pathogens, ceftazidime administered intermittently every 6 h seems an appropriate
      regimen in patients with febrile neutropenia. Larger studies are needed to
      confirm this.

PMID- 11303816
TI  - Invasive Group C Streptococcus infection associated with rhabdomyolysis and
      disseminated intravascular coagulation in a previously healthy adult.
AB  - Infections with Group C Streptococci can lead to severe disease, particularly in
      individuals with underlying illnesses such as cardiovascular disease, malignancy
      or immunosuppression. We report the first case of rhabdomyolysis and disseminated
      intravascular coagulation secondary to Group C Streptococcus in a previous
      healthy male. A toxic shock-like syndrome associated with Group C and Group G
      Streptococci has been reported. However, unlike with Group A Streptococci,
      production of endotoxins by these organisms is less well defined. We tested the
      patient's isolate for its ability to produce superantigenic toxins and to induce
      a mitogenic response. Although it is not known whether Group C Streptococci
      require special growth conditions for the production of superantigens, we could
      not demonstrate either the production of exotoxins or the induction of a
      mitogenic response.

PMID- 11303817
TI  - Infected total knee arthroplasty due to Actinomyces naeslundii.
AB  - A case of a total knee arthroplasty infection with Actinomyces naeslundii is
      described. The difficulties of therapeutic decision-making are emphasized.

PMID- 11303818
TI  - A case of disseminated Mycobacterium marinum infection following systemic steroid
      therapy.
AB  - We describe the dissemination of Mycobacterium marinum infection from the right
      middle finger to the whole extremity and two legs, with the involvement of
      tendons and joints, in a patient who was treated with a steroid when
      Mycobacterium marinum infection was not suspected. The patient was successfully
      treated with a combined surgical and medical approach.

PMID- 11303819
TI  - A case of disseminated Cryptococcosis with skin eruption in a patient with acute
      leukemia.
AB  - Disseminated cryptococcosis is a life-threatening infection caused by
      Cryptococcus neoformans and cutaneous dissemination occurs in 10-15% of patients.
      We report a case of a 49-y-old leukemic patient with disseminated cryptococcosis
      who presented with fever, headache, normal cerebrospinal fluid profile and
      multiple skin lesions mimicking molluscum contagiosum.

PMID- 11303820
TI  - Visceral leishmaniasis in an AIDS patient on successful antiretroviral therapy:
      failure of parasite eradication despite increase in CD4+ T-cell count but low
      CD8+ T-cell count.
AB  - An unusual cutaneous relapse of visceral leishmaniasis (initially mistaken for
      eruptive histiocytomas) was seen in an AIDS patient despite good virological and
      CD4+ T-cell responses to highly active antiretroviral therapy. Splenectomy and
      the patient's low CD8+ T-cell count are discussed as possible causes of failed
      disease control.

PMID- 11303821
TI  - Macrocytosis in patients on stavudine.
AB  - We retrospectively reviewed the effects on the erythrocyte mean corpuscular
      volume (MCV) of the use of stavudine-including antiretroviral regimens in both
      zidovudine-naive and zidovudine-experienced HIV-infected patients. Macrocytosis
      was commonly observed among patients on stavudine-based regimens although the MCV
      usually stabilized at a lower level than that observed with zidovudine.

PMID- 11303822
TI  - Imperfect memory and the development of Haemophilus influenzae type B disease.
AB  - Considerable evidence indicates that both anticapsular antibody and immunologic
      memory play a role in immunity to Haemophilus influenzae type b (Hib) disease.
      The efficacy of memory (or antibody) cannot be expected to be 100%; therefore
      some individuals may develop invasive disease despite their having been naturally
      primed. The proportion of cases of H. influenzae type b disease with evidence of
      immunologic memory is related to both the efficacy of memory in preventing
      disease and the age-related prevalence of memory in the population. The task is
      to discern the relative contributions of antibody and memory in conferring
      protection and to determine the extent to which natural exposure and vaccination
      establish these two effector mechanisms.

PMID- 11303823
TI  - Randomized, controlled trial comparing once daily and three times daily
      gentamicin in children with urinary tract infections.
AB  - OBJECTIVE: To undertake population pharmacokinetic modeling and to determine the
      safety and efficacy of once daily (OD) gentamicin dosing in children with severe
      urinary tract infections (UTI). METHODS: An open, randomized, controlled trial
      comparing OD with three times daily (TD) gentamicin dosing in hospitalized
      children ages 1 month to 12 years with UTI. Daily doses (milligrams per kg per
      day) of gentamicin in both groups were 7.5 (<5 years old), 6.0 (5 to 10 years
      old) and 4.5 (>10 years old). RESULTS: There were 179 children enrolled (90 OD,
      89 TD). Baseline clinical characteristics and pathogens were similar, except that
      circulatory compromise and renal cortical scintigraphic defects were more common
      in the OD group. Median gentamicin treatment durations were 3.0 (OD) and 2.7 (TD)
      days. Mean peak gentamicin concentrations were 17.3 (OD) vs. 6.4 (TD) mg/l; 99%
      of peak concentrations were >7 mg/l in the OD group whereas 16% of peak
      concentrations were <5 mg/l in the TD group. Mean trough concentrations were 0.35
      (OD) vs. 0.55 (TD) mg/l. In the OD group 4% of trough concentrations were > or =
      2 mg/l, whereas in the TD group only 0.7% were > or = 2 mg/l. Age or prior
      elevated peak concentrations did not predict high trough concentrations.
      Population pharmacokinetic modeling of the data fitted a one-compartment model
      with first order elimination. There were no clinical or bacteriologic failures.
      The two disease-related complications were confined to the OD group. No nephro-
      or ototoxicity was identified. CONCLUSIONS: With age-appropriate dosing and
      measurement of serum trough concentrations before the second dose, OD gentamicin
      is safe and effective for the treatment of UTI requiring parenteral treatment in
      children aged 1 month to 12 years.

PMID- 11303824
TI  - Antibiotic-resistant bacteria in pediatric chronic sinusitis.
AB  - BACKGROUND: Limited information exists on emerging bacterial resistance patterns
      in pediatric chronic sinusitis. METHODS: A retrospective review (1995 to 1998) of
      the aerobic microbiology of chronic sinusitis in children at a tertiary care
      children's hospital was conducted. One hundred nineteen children (mean age, 4.9
      years) with maxillary sinusitis of >8 weeks duration and no known
      immunodeficiency or cystic fibrosis who underwent antral irrigation were
      included. RESULTS: One hundred sixty-one of 240 (67%) aerobic cultures were
      positive, yielding 274 isolates. Eighty-eight positive cultures were
      polymicrobial. The most frequent isolates were nontypable Haemophilus influenzae
      (24%), Streptococcus pneumoniae (19%), Moraxella catarrhalis (17%), coagulase
      negative Staphylococcus (6%), alpha-streptococci (6%), diphtheroids (5%),
      Staphylococcus aureus (3%) and Neisseria spp. (3%). Rates of nonsusceptibility of
      Streptococcus pneumoniae were 64% for penicillin (24% high grade resistance), 40%
      for cefotaxime, 18% for clindamycin and 0% for vancomycin. Rates of
      nonsusceptibility of S. pneumoniae did not change significantly during the study
      period. Thirty-nine percent of H. influenzae isolates were beta-lactamase
      positive and 44% were nonsusceptible to ampicillin (41% high grade resistance).
      Beta-lactamase positivity of H. influenzae decreased during the study period (P =
      0.06). All M. catarrhalis isolates tested were beta-lactamase-positive.
      CONCLUSION: This study indicates that the aerobic pathogens in pediatric chronic
      sinusitis include bacteria typical of acute sinusitis as well as organisms more
      characteristic of chronic disease. Moreover it highlights the significant role of
      antibiotic-resistant aerobes, including multiply resistant S. pneumoniae, in
      pediatric chronic sinusitis.

PMID- 11303826
TI  - Respiratory tract infections in cytomegalovirus-excreting and nonexcreting
      infants.
AB  - BACKGROUND: There is evidence of an immunosuppressive effect of cytomegalovirus
      (CMV), and CMV has been claimed to be a copathogen in respiratory tract
      infections (RTI). We therefore studied the significance of CMV viral load in
      infants with RTI, compared the frequency of infection with respiratory viruses
      and followed the course of RTI in CMV-excreting vs. nonexcreting infants.
      METHODS: We examined 201 infants consecutively admitted to the Department of
      Pediatrics for RTI. At admission nasopharyngeal aspirates, throat swabs and urine
      were examined for CMV, and nasopharyngeal aspirates were examined for respiratory
      viruses. RESULTS: In these patients 23.3% had CMV in the urine, 15.3% had CMV in
      the throat and 10.9% had CMV in the nasopharynx; 26.2% excreted CMV in at least
      one site. No relationship was found between CMV viral load and clinical symptoms.
      Infection with respiratory viruses was as common in infants excreting CMV as in
      nonexcreting infants. Symptoms and the course of infection were not different in
      the two groups except that CMV-excreting infants had a significantly higher
      frequency of rhonchi at admission (P = 0.007) and a tendency for longer duration
      of cough (P = 0.06). CONCLUSION: CMV viral load was not related to clinical
      symptoms. The frequency of infection with common respiratory viruses in infants
      was independent of CMV excretion. The course of infection was not more
      complicated in infants excreting CMV; however, a higher frequency of rhonchi was
      demonstrated in patients with CMV.

PMID- 11303825
TI  - Isolation of Borrelia burgdorferi sensu lato from blood of children with solitary
      erythema migrans.
AB  - OBJECTIVES: To establish the frequency of isolation of Borrelia burgdorferi sensu
      lato from blood of children with solitary erythema migrans (EM) in Europe, to
      determine the strains of the isolated borreliae and to compare the clinical
      course and the outcome of the disease according to positive and negative blood
      culture result. METHODS: In the prospective study we included 134 consecutive
      patients younger than 15 years with solitary EM, referred to our institution in
      1996 and 1997. One milliliter of blood was withdrawn before treatment and
      cultured in modified Kelly-Pettenkofer medium. Isolated borreliae were typed
      according to LRFP analysis. Patients were treated with either penicillin V or
      cefuroxime axetil for 14 days. The posttreatment course was surveyed by follow-up
      visits during 1 year. RESULTS: B. burgdorferi sensu lato was isolated in 12 of
      134 (9%) patients. Eleven blood isolates were typed: 10 were found to be B.
      afzelii and 1 was Borrelia garinii. Comparison of blood culture-positive and 
      negative patients revealed no differences in pretreatment characteristics or in
      posttreatment clinical course. However, worsening of local and/or systemic signs
      and symptoms at the beginning of antibiotic therapy (Jarish-Herxheimer's
      reaction) was identified more often in the blood culture-positive than in the
      blood culture-negative group (5 of 12 vs. 17 of 122, respectively; P = 0.0274).
      CONCLUSIONS: The isolation rate of B. burgdorferi sensu lato from the blood of
      children with solitary EM was 9%. The majority of the isolates were B. afzelii.
      Blood culture-positive patients treated with oral antibiotics were not at greater
      risk for unfavorable course of the disease than patients with negative blood
      culture result.

PMID- 11303827
TI  - Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for
      treatment of acute otitis media.
AB  - BACKGROUND: Trimethoprim-sulfamethoxazole (T/S) has often been used as first and
      second line of treatment for acute otitis media (AOM). Because of the increasing
      resistance of Streptococcus pneumoniae and Haemophilus influenzae to T/S, we
      undertook the present study to investigate the bacteriologic and clinical
      efficacy of this drug in AOM. METHODS: Fifty-four culture-positive evaluable
      patients ages 3 to 32 months with AOM were treated with T/S 4/20 mg/kg in two
      divided daily doses for 10 days. Middle ear fluid (MEF) was cultured at
      enrollment (Day 1) and on Days 4 and 5 after initiation of treatment. Additional
      MEF cultures were obtained if clinical relapse occurred. Clinical failure was
      determined when the symptoms and signs of AOM did not improve or recurred during
      therapy. Bacteriologic failure was defined by positive culture on Days 4 and 5,
      or negative on Days 4 and 5 but positive again before the end of treatment.
      Patients were followed until Day 28 +/- 2. RESULTS: A total of 67 organisms were
      isolated from MEF specimens of the 54 study patients: S. pneumoniae, 24; H.
      influenzae, 40; and Streptococcus pyogenes, 3. Fifteen (63%) of 24 S. pneumoniae
      were nonsusceptible to T/S (trimethoprim MIC, >0.5 microg/ml), of which 10 (67%)
      were highly resistant to T/S (trimethoprim MIC, > or = 4.0 microg/ml). Twelve
      (30%) of 40 H. influenzae and all 3 S. pyogenes isolates were nonsusceptible to
      T/S (MIC > or = 4.0 microg/ml). Bacteriologic eradication occurred in 9 of 9
      (100%) and 27 of 27 (100%) T/S-susceptible S. pneumoniae and H. influenzae,
      respectively, vs. 4 of 15 (27%) and 6 of 12 (50%) T/S-nonsusceptible S.
      pneumoniae and H. influenzae, respectively (P < 0.001). The 3 patients with S.
      pyogenes failed bacteriologically. Nine new organisms, not initially isolated,
      emerged during treatment, 7 of which (77%) were resistant to T/S. Altogether
      bacteriologic failure (organisms not eradicated plus newly emerged) occurred in
      29 (53%) of 54 patients. Clinical failures occurred in 8 (15%) of 54 patients,
      and in 7 of these 8 cases the clinical failures occurred in those with
      bacteriologic failures. Ten patients relapsed clinically after completion of
      treatment and in 8 of them tympanocentesis for MEF culture was performed. Six of
      these 8 cultures were positive, and the initial pathogen was isolated in 4 of 6
      (67%). CONCLUSIONS: A high bacteriologic failure rate as well as a considerable
      clinical failure rate occurred among patients with AOM treated with T/S. We
      believe that T/S is no longer an appropriate empiric choice for the treatment of
      AOM in regions where high T/S resistance among respiratory pathogens is reported.

PMID- 11303828
TI  - Epidemiology of herpes simplex virus in children by detection of specific
      antibodies in saliva.
AB  - OBJECTIVES: To facilitate the study of the prevalence of herpes simplex virus
      (HSV) infection and its determinants in children, we developed a noninvasive
      saliva test. METHODS: A capture enzyme-linked immunosorbent assay (ELISA) for the
      detection of IgG to HSV in saliva was developed, validated against a commercial
      serum ELISA in 110 children and 187 adults and used in a cross-sectional
      population-based study including 2,048 children ages 1 to 17 years, recruited in
      day-care centers and schools of Geneva, Switzerland. Demographic and
      socioeconomic determinants of HSV prevalence were studied. RESULTS: The
      sensitivity and specificity of the saliva assay were 94.1 and 95.5%,
      respectively, compared with the commercial serum ELISA. Participation in the
      cross-sectional study was 86.6%. The overall prevalence of anti-HSV IgG was
      23.91%. It increased with age up to 7 years, reaching a plateau at 35% without
      evidence for day-care or school transmission. The main determinants of prevalence
      were region of national origin and parents' professional category. CONCLUSIONS:
      This new saliva-based assay proved its feasibility in the first population-based
      study of HSV prevalence in children that uses saliva, confirmed its validity by
      identifying determinants of prevalence consistent with previous reports and
      yielded new information, such as the lack of influence of day-care attendance, in
      the population studied.

PMID- 11303829
TI  - Tolerability and immunogenicity of an eleven-valent pneumococcal conjugate
      vaccine in healthy toddlers.
AB  - BACKGROUND: A need to increase the serotype coverage of pneumococcal conjugate
      vaccines exists. The use of a single carrier protein may cause overload of the
      carrier and decrease the immune response by not providing sufficient carrier
      specific T helper cell support. A vaccine composed of a mixture of tetanus- and
      diphtheria-conjugated polysaccharides (PS) is a potential solution to this issue.
      OBJECTIVES: The aim of this study was to assess the tolerability and
      immunogenicity in healthy toddlers of an 11-valent pneumococcal conjugate vaccine
      that uses both tetanus and diphtheria toxoids as carriers. We explored the effect
      of an aluminum adjuvant on safety and immunogenicity by comparing the vaccine
      with and without adjuvant. METHODS: Twenty Finnish and 23 Israeli toddlers
      received the conjugate vaccine with or without aluminum adjuvant. Safety data
      were recorded for 5 days after vaccination. Sera were obtained before and 28 days
      after the immunization. IgG antibodies to the 11 vaccine-type PSs were determined
      by enzyme immunoassay. RESULTS: No serious adverse events occurred. The
      formulation with the adjuvant tended to induce fewer local but more systemic
      reactions than the non-adjuvant-containing formulation. Both vaccine formulations
      induced significant IgG increases for the vaccine-specific PSs. Types 3 and 7F
      were the most immunogenic; antibodies reached a concentration of 1 microg/ml in
      all individuals. Conjugates of types 6B, 14 and 23F were the weakest immunogens;
      antibodies reached the concentration of 1 microg/ml in 36, 27 and 32% of the
      individuals in the nonadjuvant group and in 53, 38 and 53% in the adjuvant group,
      respectively. CONCLUSIONS: An 11-valent mixed carrier pneumococcal conjugate
      vaccine is safe and immunogenic in toddlers. The use of an adjuvant do not seem
      to offer any significant benefit.

PMID- 11303830
TI  - Airflow limitation during respiratory syncytial virus lower respiratory tract
      infection predicts recurrent wheezing.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection
      (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk
      factors have been identified to predict which infants will have wheezing episodes
      subsequent to RSV LRTI. OBJECTIVE: To determine clinical predictors for airway
      morbidity after RSV LRTI. METHODS: In a 1-year follow-up study we investigated
      the predictive value of auscultatory findings characteristic of airflow
      limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical
      characteristics, including the presence or absence of signs of airflow
      limitation, of hospitalized infants with RSV LRTI were prospectively recorded
      during 2 winter epidemics. During a 1-year follow-up period parents of 130
      infants recorded daily airway symptoms. OUTCOME MEASURE: Recurrent wheezing
      defined as > or = 2 episodes of wheezing. RESULTS: Signs of airflow limitation
      during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants.
      Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow
      limitation and in 51 (61%) with signs of airflow limitation during initial RSV
      LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model,
      airflow limitation during initial RSV LRTI proved independent from other clinical
      parameters, including age, parental history of asthma and smoke exposure.
      CONCLUSIONS: A sign of airflow limitation during RSV LRTI is the first useful
      clinical predictor for subsequent recurrent wheezing.

PMID- 11303831
TI  - Standard case management of pneumonia in hospitalized children in Uruguay, 1997
      to 1998.
AB  - OBJECTIVE: To report the results of the use of antimicrobial guidelines for the
      management of children with community-acquired bacterial pneumonia. METHODS:
      Admittance and discharge criteria and algorithms for diagnosis and treatment were
      established. The decision to treat with antibiotics was based on radiologic
      findings in pneumonia with pulmonary consolidation and left to the attending
      physician's criteria in the remaining cases. The use of antibiotics was limited
      to penicillin and derivatives (ampicillin, amoxicillin) and macrolides. RESULTS:
      Of the 1163 children treated as bacterial pneumonia, hospitalized in public and
      private health facilities in Montevideo from September, 1997, through September,
      1998, standard case management was applied in 1082 (93%). Age distribution was:
      <1 month, 1%; between 1 and 11 months, 29%; between 1 and 5 years, 50%; >5 years,
      20%. Chest radiography showed evidence of pulmonary consolidation in 843 children
      (73%). Bacteria were detected in blood culture and/or pleural fluid of 57
      children (5%). In 51 the identified microorganism was Streptococcus pneumoniae,
      susceptible to penicillin in 30, intermediate in 6 and resistant in 5 (maximum
      MIC, 4 microg/ml); in 10 cases etiologic diagnosis was made by antigen detection.
      Empyema was present in 62 children (5.3%); 38 (3.27%) required treatment in an
      intensive care unit; and 5 (0.4%) died. CONCLUSIONS: Compliance with standard
      case management was highly satisfactory. Outcome of children treated with
      penicillin and derivatives was good, including children with empyema and
      pneumatocele and two patients with penicillin-resistant S. pneumoniae. At the
      present time S. pneumoniae resistant to penicillin is not an important problem in
      children with pneumonia in Uruguay. Surveillance of identified microorganisms and
      their antimicrobial susceptibility must continue.

PMID- 11303832
TI  - Pneumococcal nasopharyngeal colonization in young South Indian infants.
AB  - BACKGROUND: Streptococcus pneumoniae is the most frequent bacterial cause of
      morbidity and mortality in young children. Bacteria carried in the nasopharynx of
      healthy children reflect the prevalent strains circulating in the community.
      METHODS: We recruited 464 newborns from a rural area in South India with endemic
      vitamin A deficiency. Nasopharyngeal specimens were collected from each infant at
      ages 2, 4 and 6 months. RESULTS: Fifty-four percent of study infants were
      colonized by age 2 months, with 64.1 and 70.2% carriage prevalence at ages 4 and
      6 months, respectively. The odds of carriage at 2 months were significantly
      increased in female infants, infants living in a household in which 20 or more
      cigarettes were smoked each day, infants whose mothers had less than 1 year of
      schooling and infants fed colostrum. At age 4 months infants having 2 or more
      siblings <5 years of age were at significantly increased risk of carriage. At age
      6 months none of the potential risk factors examined achieved statistical
      significance, but maternal night blindness increased the risk of colonization 3
      fold. The odds of carrying a PncCRM197 vaccine serotype were increased among
      infants born to mothers who experienced night blindness during pregnancy. The
      most prevalent serogroups/types during the first 6 months of life were 6, 9, 10,
      11, 14, 15, 19, 23 and 33, accounting for 76.7% of all serotyped isolates.
      CONCLUSIONS: South Indian infants experience high rates of pneumococcal carriage
      during the first 6 months of life, which may partially explain their increased
      risk for pneumonia.

PMID- 11303833
TI  - Effect of rotavirus vaccine on Sapporo virus gastroenteritis in Finnish infants.
AB  - BACKGROUND: Sapporo-like viruses (SLVs) occur worldwide, but there is limited
      information about the SLV-associated gastroenteritis outside Japan. METHODS:
      Stool specimens from 1,432 episodes of gastroenteritis that occurred in children
      between 2 months and 2 years of age during a rotavirus vaccine trial (776
      episodes in placebo-vaccinated and 656 in rotavirus-vaccinated infants) were
      examined for SLVs using a reverse transcription-PCR assay. The reverse
      transcription-PCR took advantage of new primers specific for Sapporo virus
      genetic clusters I, II and III; SV/SV82 (SV/Sapporo virus 82); SV/Lond92 (SV/
      London 92); and SV/PV (Parkville virus). RESULTS: SLVs were detected in
      association with 132 (9.2%) of all episodes; in 80 (5.6%) episodes SLV was the
      only gastroenteritis virus detected. The epidemic season of SLVs peaked from
      March to May concurrently with rotaviruses and astroviruses and overlapping
      withNorwalk-like viruses. Clinically SLV gastroenteritis was characterized by a
      mild diarrheal disease, being sharply different from the Norwalk-like virus
      associated "winter vomiting disease." Rotavirus vaccination did not have any
      effect on the number of SLV episodes, but the intensity and duration of SLV
      associated diarrhea were reduced in rotavirus-vaccinated children compared with
      placebo-vaccinated children (P = 0.0008). CONCLUSIONS: SLVs are common causative
      agents of acute gastroenteritis in young Finnish children. SLV disease is
      characterized by diarrhea, which is usually mild but can be severe. By an unknown
      mechanism rotavirus vaccine seems to reduce the severity of SLV-associated
      diarrhea.

PMID- 11303834
TI  - Non-type b Haemophilus influenzae disease: clinical and epidemiologic
      characteristics in the Haemophilus influenzae type b vaccine era.
AB  - BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib)
      disease caused by the widespread use of conjugate vaccines, non-type b H.
      influenzae will become a more important cause of H. influenzae (Hi) disease.
      Characterization of the clinical and epidemiologic features of non-b Hi disease
      is needed in the Hib vaccine era. METHODS: A prospective active surveillance
      study of invasive Hi disease involving pediatricians in the United Kingdom and
      Republic of Ireland. For the first phase of the study (October 1, 1992, to
      October 31, 1995) pediatricians were asked to report any child who had invasive
      Hi disease and who had received Hib conjugate vaccine. For the second phase of
      the study (November 1, 1995. To December 31, 1998) pediatricians were asked to
      report any child with invasive Hi disease regardless of vaccination status.
      RESULTS: During the study period 102 cases of invasive non-type b Hi disease and
      106 cases of invasive Hib disease were reported in children who had been fully
      vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22
      months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or
      = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than
      children with type b disease. For the last 2 years of the study invasive Hi
      disease occurring in a fully vaccinated child was more likely to be caused by a
      non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non
      type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as
      compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of
      non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi
      is a rare cause of disease in children, but in the Hib vaccine era it has become
      more common than type b as a cause of Hi disease in fully vaccinated children.

PMID- 11303835
TI  - Identification of Pneumocystis carinii in the lungs of infants dying of sudden
      infant death syndrome.
AB  - BACKGROUND: Recently Pneumocystis carinii has been identified in a significant
      number of infants diagnosed as having died from sudden infant death syndrome
      (SIDS) in South America and Europe. METHODS: We examined lung sections of 79
      infants who died with a diagnosis of SIDS in Rochester, NY, and Connecticut for
      the presence of P. carinii. RESULTS: Organisms with a characteristic silver stain
      appearance for P. carinii were identified in 14% of the lung sections.
      CONCLUSIONS: These data suggest that a possible link between some cases of SIDS
      and infection with P. carinii should be further evaluated and that infection of
      young infants may serve as an important reservoir for human P. carinii.

PMID- 11303836
TI  - Update on meningococcal vaccine.

PMID- 11303837
TI  - Current approach to invasive aspergillosis.

PMID- 11303838
TI  - Effect of protease inhibitors combined with standard antiretroviral therapy on
      linear growth and weight gain in human immunodeficiency virus type 1-infected
      children.
AB  - Children with HIV-1 infection and poor growth have a significant increase in the
      risk of death. We studied the effects of protease inhibitors on the height and
      weight of 27 HIV-1-infected children and found that in our small pilot study,
      protease inhibitor therapy had a positive effect on the heights of HIV-1-infected
      children. Accelerated height velocity was sustained for at least 18 to 20 months.

PMID- 11303839
TI  - Hemolytic-uremic syndrome surveillance to monitor trends in infection with
      Escherichia coli O157 and non-O157 enterohemorrhagic E. coli in Austria.
AB  - Austrian data underline that relying on the number of enterohemorrhagic
      Escherichia coli (EHEC) O157 strains isolated from clinical specimens does not
      allow assessment of the actual incidence of EHEC infections. A hospital-based
      system for identification of hemolytic-uremic syndrome cases based on voluntary
      cooperation was established in 1995 and provides information needed to monitor
      trends in the incidence of O157 and non-O157 EHEC infections.

PMID- 11303840
TI  - Q fever encephalitis with cytokine profiles in serum and cerebrospinal fluid.
AB  - A 7-year-old boy with acute encephalitis was proved to have Coxiella burnetii
      infection. Cerebrospinal fluid but not serum had elevated values of interleukins
      1-beta and 6, but not of tumor necrosis factor.

PMID- 11303841
TI  - Giant hepatic granuloma caused by Bartonella henselae.
AB  - We report a 10-year-old girl with a 3.0- by 3.5-cm giant hepatic granuloma caused
      by Bartonella henselae. Such a solitary and large granuloma associated with B.
      henselae infection has not been previously reported. We believe that B. henselae
      infection is a consideration in the differential diagnosis of a large hepatic
      mass.

PMID- 11303842
TI  - Ciprofloxacin-induced acute renal failure in a patient with cystic fibrosis.
AB  - Acute renal failure is a rare adverse reaction of antibiotic therapy with
      quinolones seldom seen in young patients. We report an 18-year-old young woman
      with cystic fibrosis who experienced a pronounced decline in renal function after
      oral treatment with ciprofloxacin for 3 weeks. Withdrawal of the drug led to
      normalization of renal function after 10 days.

PMID- 11303843
TI  - Ten-year-old boy with hemangiopericytoma and human immunodeficiency virus
      infection.
AB  - This report documents the first case of hemangiopericytoma in an HIV-infected
      child who is most likely a case of vertical transmission of HIV with slow
      progression to AIDS. We also raise the possibility that there is a causal
      relationship between HIV and hemangiopericytoma.

PMID- 11303844
TI  - Disseminated deep tissue infection with draining sinus tracts in a healthy seven
      year-old.

PMID- 11303845
TI  - Recommendations for dosing antibiotics.

PMID- 11303846
TI  - Cefepime microbiologic profile and update.
AB  - BACKGROUND: The evolution of the cephalosporin class of antibiotics through
      modifications of the basic cephem structure has resulted in a new generation with
      improved antibacterial activity. Cefepime is a prototypic agent of this new class
      of fourth generation cephalosporins. OBJECTIVE: To review the microbiologic
      profile of cefepime. RESULTS: Cefepime, which is a zwitterion, has a net neutral
      charge that allows it to penetrate the outer membrane of Gram-negative bacteria
      faster than third generation cephalosporins. It is more stable against beta
      lactamases because of the lower affinity of the enzymes for cefepime when
      compared with third generation cephalosporins. As a result of these structural
      attributes, cefepime has in vitro activity against pathogens that are prevalent
      in pediatric infections. This agent offers the advantage of Gram-positive
      coverage similar to that of cefotaxime and ceftriaxone, as well as good activity
      against Pseudomonas aeruginosa and many enteric bacilli that are resistant to
      third generation cephalosporins, including clinical isolates of Enterobacter spp.
      and Citrobacter freundii. CONCLUSIONS: Based on its spectrum of activity cefepime
      is an option for the treatment of pediatric infections caused by susceptible
      pathogens.

PMID- 11303847
TI  - Review of the pharmacokinetics of cefepime in children.
AB  - BACKGROUND: Because determining the pharmacokinetics of drugs used in pediatric
      patients allows for appropriate dosing and optimal clinical response, we have
      reviewed the pharmacokinetic data on the use of cefepime in the pediatric
      population. METHODS: Three studies encompassing 88 patients ages 2 months to 16
      years examined the pharmacokinetics of cefepime given as a single iv dose, as
      multiple iv doses and by im administration. In all studies serial blood and urine
      or cerebrospinal fluid (CSF) samples were collected after a single dose and/or at
      steady state, defined as after at least 2 days of dosing. Pharmacokinetic
      parameters were generated from concentration-vs.-time curves and were analyzed
      using noncompartmental methods. RESULTS: In all studies cefepime exhibited a
      linear pharmacokinetic profile and concentrations declined proportionally over
      time. Minimal accumulation was observed after multiple dosing. Pharmacokinetic
      parameters were similar in all studies and appeared to be dose-independent. Mean
      (range) parameters observed in this review were: t 1/2 = 1.7 h (1.26 to 1.93);
      volume of distribution at steady state, 0.37 liter/kg (0.33 to 0.40); total body
      clearance, 3.1 ml/min/kg (1.43 to 4.01); renal total body clearance, 2.3
      ml/min/kg (1.86 to 3.05); absolute bioavailability of cefepime after the im dose,
      82.3%; and urinary recovery, 72% (57 to 85%). Penetration into CSF appeared to be
      good, with CSF concentrations averaging 3.3 to 5.7 microg/ml 0.5 and 8 h after
      administration of the dose, respectively. CONCLUSION: Cefepime displayed a linear
      pharmacokinetic profile, was well-absorbed via im injection and had adequate
      penetration into the CSF of patients with bacterial meningitis, compared with
      other beta-lactams.

PMID- 11303849
TI  - Empiric use of cefepime in the treatment of serious urinary tract infections in
      children.
AB  - BACKGROUND: Urinary tract infections (UTIs) are common in childhood. They
      represent a significant proportion (10%) of hospital-acquired infections in
      children. Bacteria causing UTIs in children vary, depending on the setting
      (community-acquired vs. nosocomial), underlying anatomic anomalies and concurrent
      medical conditions. OBJECTIVE: To review published and unpublished clinical
      studies that have used cefepime for the treatment of UTIs in children. METHODS
      AND RESULTS: In two recent multicenter, randomized trials, cefepime (50
      mg/kg/dose every 8 h and every 12 h) was compared with ceftazidime (50 mg/kg/dose
      every 8 h) for the treatment of serious urinary tract infections including
      pyelonephritis in children less than 12 years of age. In these studies a
      favorable clinical and microbiologic response was observed in >95% of cefepime
      treated and ceftazidime-treated children assessed at the end of treatment.
      CONCLUSIONS: These results indicate that cefepime represents an important
      therapeutic option for the treatment of serious UTIs in children.

PMID- 11303848
TI  - Empiric use of cefepime in the treatment of lower respiratory tract infections in
      children.
AB  - BACKGROUND: These studies were designed to assess the efficacy and safety of
      cefepime, a fourth generation cephalosporin, for the treatment of serious
      infections, including lower respiratory tract infections (LRTI) in children.
      METHODS: Four clinical trials of cefepime for the treatment of serious bacterial
      infections enrolled 259 children with LRTI. In 3 trials cefepime was compared
      with ceftazidime (n = 166), cefotaxime (n = 16) or cefuroxime (n = 12). One trial
      was noncomparative (n = 65). RESULTS: Treatment with cefepime 50 mg/kg/ dose
      administered every 8 to 12 h produced a satisfactory clinical response (clinical
      signs of infection resolved or improved with no evidence of recurrent infection
      at posttreatment follow-up) in 88 to 100% of patients, comparable with comparator
      therapy. In children from whom a causative pathogen was identified, bacteriologic
      eradication was comparable between cefepime and comparator therapy. Cefepime was
      as safe and well-tolerated as comparator therapy. Few treatment-related clinical
      or laboratory adverse events were noted and were equivalent to comparator in all
      studies. CONCLUSION: Cefepime is as effective, safe and well-tolerated for the
      empiric treatment of children with LRTI as comparator agents but offers the
      advantage of an enhanced spectrum of activity for Gram-positive and Gram-negative
      pathogens compared with second or third generation cephalosporins.

PMID- 11303850
TI  - Cefepime in the empiric treatment of meningitis in children.
AB  - BACKGROUND: Because the introduction of extended spectrum cephalosporins into
      pediatric practice offers a number of choices for treatment, we review efficacy
      studies of cefepime monotherapy in the treatment of bacterial meningitis in
      children. METHODS: Two open, randomized, comparative studies assessed the
      efficacy of cefepime empiric monotherapy in the treatment of bacterial meningitis
      in 345 pediatric patients. These studies were conducted in Latin America and
      compared cefepime (50 mg/kg/dose every 8 h) with either cefotaxime (50 mg/kg/dose
      every 6 h) or ceftriaxone (50 mg/kg/dose every 12 h). Patients 2 months to 14
      years old who had clinical signs and symptoms consistent with a central nervous
      system infection were enrolled. Efficacy was based on clinical and bacteriologic
      response. RESULTS: Integrated results from the Latin American studies indicated a
      75% cure rate with cefepime vs. a 78% cure rate with comparator, among evaluable
      patients. Overall the rate of treatment failure was 12%. Haemophilus influenzae
      had the highest bacterial eradication rate (97% overall), and rates were
      comparable in cefepime and comparator arms. Eradication rates for Neisseria
      meningitidis were equally high in both treatment arms (95% overall), and the
      eradication rate for Streptococcus pneumoniae was 92% overall. Of the patients
      with S. pneumoniae isolated during pretreatment (from either cerebrospinal fluid
      or blood), 11 (16 isolates in total) had their isolates tested against penicillin
      and all were susceptible. Presence or absence of seizures, level of
      consciousness, Glasgow Coma Score and duration of signs and symptoms were strong
      predictors of outcome. Collectively no specific safety concerns were identified.
      CONCLUSION: Cefepime represents an important therapeutic option for the empiric
      treatment of bacterial meningitis in children, based on the good clinical
      response and bacteriologic eradication rates observed in this review.

PMID- 11303852
TI  - Recent advances in external skeletal fixation.
AB  - While the use of external skeletal fixation was once associated with substantial
      postoperative morbidity, clinical and experimental studies have led to
      technological advances and modifications in application techniques that have
      greatly improved the results obtained with this treatment modality. The past
      decade saw numerous advances in external skeletal fixator implants, components
      and instrumentation, including improvements in fixation pin design, and the
      development of new linear external skeletal fixation systems and economical
      circular external skeletal fixation systems specifically engineered for use in
      dogs and cats. In addition, a greater understanding of fixator biomechanics and
      the pathobiology of the bone-fixation pin interface have improved fixator
      application practices. This article reviews many of the more significant recent
      advances in external skeletal fixation.

PMID- 11303851
TI  - Comparative study of cefepime versus ceftazidime in the empiric treatment of
      pediatric cancer patients with fever and neutropenia.
AB  - BACKGROUND: In view of the recent trend toward monotherapy in the treatment of
      bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs.
      ceftazidime for the empiric treatment of febrile episodes in neutropenic
      pediatric cancer patients. METHODS: In a single site, open label study, 104
      neutropenic pediatric cancer patients [96% with absolute neutrophil count (ANC)
      of <500 neutrophils/mm3] with a median age of 6 years were randomized (1:1) to
      receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or
      = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring
      at least twice in 24 h, or single >38.5 degrees C). Febrile episodes were
      classified as either microbiologically or clinically documented infection or
      fever of unknown origin. Therapy continued until the ANC was > or = 1,000
      neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum
      duration of treatment, 8 weeks). The primary efficacy endpoints assessed were
      clinical and microbiologic response to assigned drug therapy. Secondary outcome
      measures were rate of early discontinuation of study drug and use of concomitant
      antibiotic therapy to modify initial study drug regimen. RESULTS: Of 68 patients
      who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients
      and 70% (23 of 33) of ceftazidime-treated patients responded to treatment. The
      small number of study patients precluded statistical analysis of results. In a
      modified intent-to-treat analysis, 59% of the patients treated with cefepime and
      47% of ceftazidime-treated patients responded to therapy. Cefepime patients
      developed fewer new infections than ceftazidime patients (9% vs. 21%,
      respectively) and early discontinuation of study drug therapy occurred slightly
      more often in the ceftazidime group. Further, the use of concomitant systemic
      antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime
      treated patients, as compared with the ceftazidime group [35% [17 of 49] vs. 44%
      (24 of 55), respectively]. No deaths or serious adverse events were considered to
      be related to study therapy. The most frequent adverse event was rash that was
      moderate in severity, and it occurred equally in both groups. CONCLUSION:
      Cefepime appears to be safe and effective compared with ceftazidime for initial
      empiric therapy of febrile episodes in neutropenic pediatric cancer patients.

PMID- 11303853
TI  - Use of endogenous ACTH concentration and adrenal ultrasonography to distinguish
      the cause of canine hyperadrenocorticism.
AB  - Twenty-nine dogs were diagnosed with hyperadrenocorticism (HAC). A single
      determination of endogenous plasma adrenocorticotropic hormone (ACTH) and adrenal
      ultrasonography were used in a prospective study to differentiate between
      pituitary-dependent HAC (PDH) and adrenal-dependent HAC (ADH). In 27 out of the
      29 dogs (93 per cent), both endogenous plasma ACTH concentrations and adrenal
      ultrasonography indicated the same cause of HAC. Twenty-one of the 29 cases (72
      per cent) were shown to be pituitary-dependent; all had plasma ACTH
      concentrations of greater than 28 pg/ml (reference range 13 to 46 pg/ml) and both
      adrenal glands were ultrasonographically of similar size and of normal shape. All
      21 cases responded well to mitotane therapy. Six cases (21 per cent) were shown
      to be adrenal-dependent; all had plasma ACTH concentrations below the limit of
      the assay (<5 pg/ml) and the presence of an adrenal mass on ultrasonography. The
      sensitivity and specificity of adrenal ultrasonography and endogenous ACTH
      determinations to identify the cause of HAC were demonstrated to be 100 per cent
      and 95 per cent, respectively, for ADH. These discriminatory tests are more
      accurate than published figures for dexamethasone suppression testing.

PMID- 11303854
TI  - Feline hypertension: clinical findings and response to antihypertensive treatment
      in 30 cases.
AB  - Systolic hypertension was diagnosed in 30 cats. At diagnosis, 16 of those were
      found to be in chronic renal failure only, while five were azotaemic and either
      receiving treatment for hyperthyroidism (four cases) or were untreated
      hyperthyroid cases (one case). Two cases were untreated hyperthyroid cases with
      no evidence of azotaemia and the remaining seven cases had no definitive
      diagnosis of the underlying cause of their hypertension. The successful treatment
      used for the majority of cases was amlodipine, which lowered systolic blood
      pressure from 202.5+/-16.8 to 153.2+/-21.6 mmHg (mean+/-SD; n=29) within the
      first 50 days. Each case was followed for at least three months, or to the end of
      its natural life, and each cat was re-examined every six to eight weeks. Systolic
      blood pressure was kept below a target value of 165 mmHg in 58 per cent of cases
      treated for three months or longer. At the time of writing, 19 of the cases had
      died or been euthanased with a median treatment time of 203 days, one case was
      lost to follow-up and 10 cases were still alive, nine of which had been treated
      for six months or more. Amlodipine can be used for long-term control of feline
      systemic hypertension.

PMID- 11303855
TI  - Parathyroid hormone, haematological and biochemical parameters in relation to
      dental disease and husbandry in rabbits.
AB  - During a two-year period between 1995 and 1997, over 80 blood samples were
      collected from pet rabbits in order to investigate an apparent osteodystrophy
      affecting the skulls of rabbits with acquired dental disease. A series of
      haematological and biochemical analyses relating to calcium metabolism were
      performed and samples were taken for parathyroid hormone (PTH) assay. The rabbits
      were categorised according to the condition of their teeth and the manner in
      which the pets were kept. PTH concentrations were higher and calcium
      concentrations lower in hutch-kept rabbits with advanced dental disease in
      comparison with those kept in free-range conditions. No dental problems were
      detected in the free-range rabbits on radiological or clinical examination.
      During the course of the study, differences in haematological pictures and
      albumin values emerged among rabbits kept under the different husbandry regimes.
      Complete blood counts from free-range rabbits were comparable with laboratory
      reference ranges, whereas there were significantly lower red cell and lymphocyte
      counts in rabbits exhibiting advanced dental disease. Serum albumin values were
      significantly higher in rabbits kept in free-range conditions than in those with
      advanced dental disease or those unaffected by dental disease but kept in
      hutches. Rabbits kept in hutches showed trends towards anaemia and lymphopenia.
      Results indicated that acquired dental disease of pet rabbits is related to
      husbandry and is associated with alterations in calcium metabolism.

PMID- 11303857
TI  - Canine hypertrophic osteoarthropathy associated with a malignant Sertoli cell
      tumour.
AB  - A 15-year-old crossbred dog was presented with a severe cough of acute onset and
      an enlarged right testis. Symptomatic treatment for presumed 'kennel cough'
      failed to produce any improvement and at re-examination the dog had developed a
      swollen right forelimb. Radiographic examination suggested a diagnosis of
      hypertrophic pulmonary osteoarthropathy (Marie's disease) associated with
      pulmonary metastases from a testicular tumour. The dog was re-presented five days
      later with acute-onset severe vomiting and the owner elected for euthanasia.
      Necropsy was performed and histopathological assessment confirmed the presence of
      a Sertoli cell tumour in the right testis with multiple pulmonary and renal
      metastases. Hypertrophic pulmonary osteoarthropathy is a rare complication of
      metastatic canine Sertoli cell tumour. The authors know of no previously reported
      cases.

PMID- 11303856
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy in a Siberian husky.
AB  - A seven-month-old male Siberian husky was presented with a recent history of
      anorexia, hindlimb weakness and syncope. Physical examination revealed severe
      tachycardia, tachypnoea and dyspnoea. Mucous membranes were pale and femoral
      pulses were weak. An electrocardiogram showed sustained ventricular tachycardia
      with a left bundle branch block configuration. Thoracic radiographs revealed
      slight right ventricular enlargement and two-dimensional echocardiography
      revealed mild right ventricular dilation at the cardiac apex and some
      hyperechogenic areas on the right side of the interventricular septum.
      Administration of intravenous lignocaine converted the ventricular tachycardia to
      sinus rhythm. The maintenance antiarrhythmic therapy consisted of oral
      procainamide and propranolol. Three weeks later the dog died suddenly. On
      postmortem examination, the right ventricular free wall was very thin at the
      apex, infundibulum and caudal aspect of the right ventricular parietal wall,
      similar to the 'triangle of dysplasia' of human patients. Histopathological
      examination revealed replacement of several areas of right ventricular free wall
      myocardium with connective tissue and fat. The right atrium and left ventricle
      were less severely affected by the same lesions. The clinical and pathological
      findings are similar to those reported in young people with arrhythmogenic right
      ventricular dysplasia/cardiomyopathy.

PMID- 11303858
TI  - Hepatic arteriovenous fistulae and portal vein hypoplasia in a Labrador
      retriever.
AB  - An 18-month-old male Labrador retriever was referred for investigation of chronic
      intermittent diarrhoea and vomiting of two months duration. A diagnosis of
      hepatic arteriovenous fistulae was made. These are extremely rare hepatic
      vascular anomalies which confer arterial pressure to the portal vein. Liver
      atrophy, portal vein hypoplasia, portal hypertension and multiple acquired
      portosystemic collateral vessels are the main complications. Surgical excision is
      a challenge as resection of large lesions may be associated with significant
      blood loss. In this dog, persistence of portal vein hypoplasia and extensive
      collateral pathways following surgery led to a reserved prognosis.

PMID- 11303859
TI  - BSAVA's evidence to the dispensing review.

PMID- 11303860
TI  - Clinical controversies at Congress 2001.

PMID- 11303861
TI  - Dendromesogens: liquid crystal organizations of poly(amidoamine) dendrimers
      versus starburst structures.
AB  - A new series of liquid crystalline poly(amidoamine) (PAMAM) dendrimers is
      described. These dendrimers are made by attaching to the 0-, 1-, 2-, 3-, and 4
      generation of PAMAM-terminal promesogenic units that carry two decyloxy chains in
      the 3- and 4-positions of their peripheral aromatic ring. X-ray diffraction
      studies show that all the compounds display a hexagonal columnar mesophase. A
      high density of aliphatic chains imposes a curved interface with the promesogenic
      units that forces the molecules to adopt a radial conformation, and therefore,
      the columnar structure. A model for the supramolecular organization of the
      different generations within the columnar mesophase is proposed based on the
      variation of some of the structural parameters.

PMID- 11303862
TI  - New auxiliaries for copper-catalyzed asymmetric Michael reactions: generation of
      quaternary stereocenters at room temperature.
AB  - Dialkyl amides of L-valine, L-isoleucine, and L-tert-leucine (2) are excellent
      chiral auxiliaries for the construction of quaternary stereocenters at ambient
      temperature. Enaminoesters 3, prepared from these auxiliaries 2 and Michael
      donors 1, undergo a copper-catalyzed asymmetric Michael reaction with methyl
      vinyl ketone (MVK, 4) to afford products 5 in 70-90% yield and 90-99% ee
      (enantiomeric excess). The exclusion of moisture or oxygen is not necessary. The
      auxiliaries 2 are readily available by standard procedures. After workup they can
      be recovered almost quantitatively.

PMID- 11303863
TI  - Multimode-photochromism based on strongly coupled dihydroazulene and
      diarylethene.
AB  - Synthesis and photophysical/photochemical investigations of 1,8a-dihydro-2,3
      bis(2,5-dimethy-3-thienyl)-azulene-1,1-dicarbonitrile (1A) and 1,8a-dihydro-2,3
      diphenylazulene-1,1-dicarbonitrile (2A) are reported. The photoprocesses and
      thermal reactions of systems 1 and 2 were studied by time-resolved and steady
      state techniques under various conditions. The dihydroazulene (DHA)
      dithienylethene (DTE) conjugate 1A is photochemically converted into the
      dihydrothienobenzothiophene (DHB) isomer 1C and the vinylheptafulvene (VHF)
      isomer 1B. System 2 exhibits exclusively DHA/VHF photochromism. For both systems
      the VHF form thermally reverts back into the DHA form. Their rate constant (kB-
      >A) increases with the solvent polarity and the relaxation kinetics proceed by
      means of an activation barrier of 65-80 kJ mol(-1); kB-->A and the activation
      parameters of the isomerisation reactions are rather similar. The photostationary
      state of the 1A-->1B and 1A-->1C photoisomerisation is sensitive to the
      irradiation wavelength. The concept of cycloswitching is discussed.

PMID- 11303864
TI  - Synthesis and characterization of germanium, tin, phosphorus, iron, and rhodium
      complexes of tris(pentafluorophenyl)corrole, and the utilization of the iron and
      rhodium corroles as cyclopropanation catalysts.
AB  - The germanium(IV), tin(IV). and phosphorus(v) complexes of
      tris(pentafluorophenyl)corrole were prepared and investigated by electrochemistry
      for elucidation of the electrochemical HOMO-LUMO gap of the corrole and the
      spectroscopic characteristics of the corrole pi radical cation. This information
      was found to be highly valuable for assigning the oxidation states in the various
      iron corroles that were prepared. Two iron corroles and the rhodium(I) complex of
      an N-substituted corrole were fully characterized by X-ray crystallography and
      all the transition metal corroles were examined as cyclopropanation catalysts.
      All iron (except the NO-ligated) and rhodium corroles are excellent catalysts for
      cyclopropanation of styrene, with the latter displaying superior selectivities.
      An investigation of the effect of the oxidation state of the metal and its
      ligands leads to the conclusion that for iron corroles the catalytically active
      form is iron(III), while all accesible oxidation states of rhodium are active.

PMID- 11303865
TI  - C-C versus C-O anionic domino cycloalkylation of stabilized carbanions: facile
      one-pot stereoselective preparation of functionalized bridged bicycloalkanones
      and cyclic enol ethers.
AB  - alpha,alpha'-Diactivated cyclic- or acyclic ketones undergo a chemoselective base
      promoted (K2CO3, DBU) one-pot C-C cycloalkylation, with 1,3- and 1,4-dihalides
      having a cis-like fixed configuration. This reaction gives highly functionalized
      bicyclo[3.2.1]octan-9-one and bicyclo[4.2.1]nonan-9-one derivatives, which are
      easily transformed to seven- and eight-membered rings through a high yield retro
      Dieckmann cleavage. Starting from trans-1,4-dibromo-2-butenes, the transformation
      is governed by stereoelectronic factors and leads, through a chemo- and
      stereoselective C-O cycloalkylation, to synthetically valuable monocyclic or
      fused polycyclic functionalized enol ethers of high synthetic value.
      Semiempirical calculations showed a small difference in energy and the late
      character of the transition states leading to cis and trans isomers of the
      corresponding fused polycyclic enol ethers. These results, although minimizing
      the influence of a destabilizing 1,3-interaction on the outcome of the reaction,
      are qualitatively in agreement with the experimental results.

PMID- 11303866
TI  - Toward direct determination of conformations of protein building units from
      multidimensional NMR experiments part II: a theoretical case study of formyl-L
      valine amide.
AB  - Chemical shielding anisotropy tensors have been determined for all twenty-seven
      characteristic conformers of For-L-Val-NH2 using the GIAO-RHF formalism with the
      6-31 + G* and TZ2P basis sets. The individual chemical shifts and their
      conformational averages have been compared to their experimental counterparts
      taken from the BioMagnetic Resonance Bank (BMRB). At the highest level of theory
      applied, for all nuclei but the amide proton, deviations between statistically
      averaged theoretical and experimental chemical shifts are as low as 1-3%.
      Correlated chemical shift plots of selected nuclei, as function of the respective
      phi, psi, chi1, and chi2 torsional angles, have been generated. On two
      dimensional chemical shift-chemical shift plots, for example, 1H(NH)-15N(NH) and
      15N(NH)-13Calpha, regions corresponding to major conformational clusters have
      been identified, providing a basis for the quantitative identification of
      conformers from NMR shift data. Experimental NMR resonances of nuclei of valine
      residues have been deduced from 18 selected proteins, resulting in 93 1Halpha
      13Calpha chemical shift pairs. These experimental results have been compared to
      relevant ab initio values revealing remarkable correlation between the two sets
      of data. Correlations of 1Halpha and 13Calpha values with backbone conformational
      parameters (phi and psi) have also been found for all pairs (e.g. 1Halpha/phi and
      13Calpha/phi) but 1Halpha/psi. Overall, the appealing idea of establishing
      backbone folding of proteins by employing chemical shift information alone,
      obtained from selected multiple-pulse NMR experiments (e.g. 2D-HSQC, 2D-HMQC, and
      3D-HNCA), has received further support.

PMID- 11303867
TI  - Size-selective electrochemical preparation of surfactant-stabilized Pd-, Ni- and
      Pt/Pd colloids.
AB  - A detailed study concerning the size-selective electrochemical preparation of
      R4N+Br- -stabilized palladium colloids is presented. Such colloids are readily
      accessible using a simple electrolysis cell in which the sacrificial anode is a
      commercially available Pd sheet, the surfactant serving as the electrolyte and
      stabilizer. It is shown that such parameters as solvent polarity, current
      density, charge flow, distance between electrodes and temperature can be used to
      control the size of the Pd nanoparticles in the range 1.2-5 nm. Characterization
      of the Pd colloids has been performed using transmission electron microscopy
      (TEM), small angle X-ray scattering (SAXS) and X-ray powder diffractometry (XRD)
      evaluated by Debye-function-analysis (DFA). Possible mechanisms of particle
      growth are discussed. Experiments directed towards the size-selective
      electrochemical fabrication of (n-C6H13)4N+Br- -stabilized nickel colloids are
      likewise described. Finally, a new strategy for preparing bimetallic colloids
      (e.g., Pt/Pd nanoparticles) electrochemically is presented, based on the use of a
      preformed colloid (e.g., (n-C8H17)4N+Br- -stabilized Pt particles) and a
      sacrificial anode (e.g., Pd sheet).

PMID- 11303868
TI  - Selective adhesion of endothelial cells to artificial membranes with a synthetic
      RGD-lipopeptide.
AB  - A constrained cyclic ArgGly-Asp-D-Phe-Lys, abbreviated as cyclo(-RGDfK-),
      lipopeptide has been synthesized and incorporated into artificial membranes such
      as giant vesicles with DOPC and solid-supported lipid bilayers. The selective
      adhesion and spreading of endothelial cells of the human umbilical cord on solids
      functionalized by membranes with this RGD-lipopeptide have been observed.
      Furthermore, we have demonstrated strong selective adhesion of giant vesicles to
      endothelial cells through local adhesion domains by combined application of
      hydrodynamic flow field and reflection interference contrast microscopy (RICM).
      The adhesion can be inhibited by competition with a water-soluble RGD peptide. We
      suggest that this strategy could improve the efficiency of liposomes targeting
      used as vectors or as drug carriers to cells.

PMID- 11303869
TI  - Geometrical structure of yttrium and metal-bromine complexes in solution:
      limitations of extended X-ray absorption fine structure analysis (EXAFS).
AB  - An extensive study on the appearance of multi-electron features in the X-ray
      absorption spectra of several yttrium(III)-based compounds has been performed.
      The existence of a multi-electron transition of non-negligible intensity within
      the extended X-ray absorption fine structure (EXAFS) region of the Y K-edge
      spectra has been proven. The impact of such features in the EXAFS analysis is
      made evident for aqueous solutions of YBr3 x 6H2O in liquid and glassy states in
      the concentration range 0.005-2.0 M, in which this transition induces an
      overestimation in the coordination numbers derived from EXAFS. We have performed
      theoretical computation of cross-sections for the double-electron processes at
      the K-edge of both Y and Br. These computations have been applied to the
      experimental EXAFS K-edge spectra of both Y and Br in several solids and in
      aqueous solutions. While in the case of Y K-edge spectra the presence of such
      multi-electron transitions was seen to seriously affect the standard EXAFS
      analysis, its influence in the case of Br K-edge spectra was determined to be
      negligible.

PMID- 11303870
TI  - Cobaltocenium-functionalized poly(propylene imine) dendrimers: redox and
      electromicrogravimetric studies and AFM imaging.
AB  - The first four generations of cobaltocenium-functionalized, diaminobutane-based
      poly(propylene imine) dendrimers DAB-dend-Cb,(PFb)x (x = 4, 8, 16, and 32;
      Cb=[Co(eta5-C5H4CONH)(eta5-C5H5)] (1-4) have been synthesized and characterized.
      The redox activity of the cobaltocenium centers in 1-4 has been characterized by
      using cyclic voltammetry and the electrochemical quartz-crystal microbalance
      (EQCM). All of the dendrimers exhibit reversible redox chemistry associated with
      the cobaltocenium/cobaltocene redox couple. Upon reduction. the dendrimers
      exhibit a tendency to electrodeposit onto the electrode surface, which is more
      pronounced for the higher generations. Pt and glassy carbon electrodes could be
      modified with films derived from 1-4,exhibiting a well-defined and persistent
      electrochemical response. EQCM measurements show that the dendrimers adsorb, at
      open circuit, onto platinum surfaces at monolayer or submonolayer coverage.
      Cathodic potential scanning past -0.75 V at which the cobaltocenium sites are
      reduced, gave rise to the electrodeposition of multilayer equivalents of the
      dendrimers. The additional material gradually desorbs upon re-oxidation so that
      only a monolayer equivalent remains on the electrode surface. Changes in film
      morphology as a function of dendrimer generation and surface coverage were
      studied by using admittance measurements of the quartz-crystal resonator on the
      basis of its electrical equivalent circuit, especially in terms of its resistance
      parameter. In general, we find that films of the lower dendrimer generation 1
      behave rigidly, whereas those of the higher generation 4 exhibit viscoelastic
      behavior with an intermediate behavior being exhibited by 2 and 3. Using tapping
      mode atomic force microscopy (AFM). we have been able to obtain molecularly
      resolved images of dendrimer 4 adsorbed on a Pt(111) electrode.

PMID- 11303871
TI  - Synthesis of pseudopeptides with sulfoximines as chiral backbone modifying
      elements.
AB  - The synthesis of pseudopeptides with a chiral alpha-sulfonimidoylcarboxy moiety
      in the backbone is described. Starting from readily available (Ss)-S-methyl S
      phenyl sulfoximine and various cyclic and acyclic alpha-amino acids the desired
      products are obtained in good yields with peptide coupling methodology. Specific
      secondary structures caused by intramolecular hydrogen bonds may be adopted.
      Results of NMR studies to reveal conformational preferences will be discussed.

PMID- 11303872
TI  - Chemical synthesis of lymphotactin: a glycosylated chemokine with a C-terminal
      mucin-like domain.
AB  - The synthesis of a 93-residue chemokine, lymphotactin, containing eight sites of
      O-linked glycosylation, was achieved using the technique of native chemical
      ligation. A single GalNAc residue was incorporated at each glycosylation site
      using standard Fmoc-chemistry to achieve the first total synthesis of a mucin
      type glycoprotein. Using this approach quantities of homogeneous material were
      obtained for structural and functional analysis.

PMID- 11303873
TI  - Syntheses and properties of zinc and calcium complexes of valinate and
      isovalinate: metal alpha-amino acidates as possible constituents of the early
      Earth's chemical inventory.
AB  - We have studied the ligand behavior of racemic isovalinate (iva) and valinate
      (val) towards zinc(II) and calcium(II). The following solid metal amino acidates
      were obtained from aqueous solutions: Zn3Cl2(iva)4 (1), Zn3Cl2(val)4 (2).
      Zn(val)2 (3), Zn(iva)2 x 2H2O (4), Zn(iva)2 x 3.25H2O (5), Zn(iva)2 (6),
      Ca(iva)2x xH2O (7), and Ca(val)2 x H2O (8). Except for complex 3, these were
      hitherto unknown compounds. The conditions under which they formed, together with
      current ideas of the conditions on early Earth, support the assumption that alpha
      amino acidate complexes of zinc and calcium might have belonged to early Earth's
      prebiotic chemical inventory. The zinc isovalinates 1, 4, and 5 were
      characterized by X-ray crystal structure analyses. Complex 1 forms a layer
      structure containing four- and five-coordinate metal atoms, whereas the zinc
      atoms in 4 and 5 are five-coordinate. Compound 5 possesses an unprecedented
      nonpolymeric structure built from cyclic [Zn6(iva)12] complexes, which are
      separated by water molecules. The thermolyses of solids 1. 3, and 8 at 320
      degrees C in an N2 atmosphere yielded numerous organic products, including the
      cyclic dipeptide of valine from 3 and 8. Condensation, C-C bond breaking and bond
      formation, aromatization, decarboxylation, and deamination reactions occurred
      during the thermolyses. Such reactions of metal-bound a-amino acidates that are
      abiotically formed could already have contributed to an organic-geochemical
      diversity before life appeared on Earth.

PMID- 11303874
TI  - Catalytic asymmetric olefin metathesis.
AB  - This paper provides a survey of the first examples of efficient catalytic
      enantioselective olefin metathesis reactions. Mo-catalyzed asymmetric ring
      closing (ARCM) and ring-opening (AROM) reactions allow access to myriad optically
      enriched compounds that are otherwise difficult to access.

PMID- 11303875
TI  - Syntheses, structure, and reactivity of chiral titanium compounds: procatalysts
      for olefin polymerization.
AB  - Titanium complexes with chelating alkoxo ligands have been synthesised with the
      aim to investigate titanium active centres in catalytic ethylene polymerisation.
      The titanium complexes cis-[TiCl2(eta2-maltolato)2] (1, 89%), and cis-[TiCl2(eta2
      guaiacolato)2] (2, 80%) were prepared by direct reaction of TiCl4 with maltol and
      guaiacol in toluene. The addition of maltol to [Ti(OiPr)4] in THF results in the
      formation of species [Ti(OiPr)2(maltolato)2] (3, 82%). The titanium compound cis
      [Ti(OEt)2(eta2-maltolato)2] (4, 74%) was obtained by the transesterification
      reaction of species 3 with CH3CO2Et. When compound 4 is dissolved in THF a
      dinuclear species [Ti2(mu-OEt)2(OEt)4-(eta2-maltolato)2] (5, 45%) is formed.
      Reaction of [Ti(OiPr)4] with crude guaiacol in THF yields a solid, which after
      recrystallisation from acetonitrile gives [Ti4(mu-O)4(eta2-guaiacolato)] x 4CH3CN
      (6, 55%). In contrast, reaction of TiCl4 with crude guaiacol in tetrahydrofuran
      affords [Ti2(mu-O)Cl2(eta2-guaiacolato)4] (7, 82%). Crystallographic and
      electrochemical analyses of these complexes demonstrate that maltolato and
      guaiacolato ligands can be used as a valuable alternative for the
      cyclopentadienyl ring. These complexes have been shown to be active catalysts
      upon combination with the appropriate activator.

PMID- 11303876
TI  - An enzyme-labile safety catch linker for synthesis on a soluble polymeric
      support.
AB  - The development of new and broadly applicable linker groups which are stable
      under a variety of reaction conditions and allow release of the desired products
      from the solid support under very mild conditions is of great interest in organic
      synthesis and combinatorial chemistry. We describe an enzyme-labile safety-catch
      linker which releases alcohols and amines through i) enzymatic cleavage of an
      amino group and ii) subsequent lactam formation. The linker group was
      investigated on different polymeric supports: TentaGel. PEGA, CPG-beads and the
      soluble polymer POE-6000. From these linker-polymer conjugates 2-methoxy-5
      nitrobenzyl alcohol was released by penicillin G acylase catalysed cleavage of a
      phenylacetamide and attack of the liberated benzylamine on the neighbouring ester
      group in ortho position. The model study revealed that only in the case of
      soluble POE-6000 conjugate high yields for the cleavage could be achieved. In the
      case of the other solid supports the enzyme does not have access to the interior
      of the polymer matrix. The application of the POE-6000 linker conjugate was
      investigated for various esters in Pd0-catalysed Heck-, Suzuki- and Sonogashira
      reactions as well as in a Mitsunobu reaction and cycloadditions. These studies
      proved that the linker is stable under a broad variety of reaction conditions and
      that the enzymatic method allows for release of the desired product alcohols
      under extremely mild conditions at pH 7 and 37 degrees C. In addition, the
      enzymatic reaction proceeds with complete chemoselectivity, that is other esters
      or amides are not attacked by the biocatalyst. In addition to alcohols amines can
      also be cleaved by means of the enzyme-initiated two-step process. In these cases
      the higher stability of amides as compared to esters requires warming to 60
      degrees C to induce cyclization and release of the desired product.

PMID- 11303877
TI  - Photochemistry of the pi-extended 9,10-bis(1,3-dithiol-2-ylidene)-9,10
      dihydroanthracene system: generation and characterisation of the radical cation,
      dication, and derived products.
AB  - Flash photolysis of bis[4.5-di(methylsulfanyl) 1,3-dithiol-2-ylidene]-9,10(
      dihydroanthracene (1) in chloroform leads to formation of the transient radical
      cation species 1.+ which has a diagnostic broad absorption band at lambdamax
      approximately 650 nm. This band decays to half its original intensity over a
      period of about 80 micros. Species 1.+ has also been characterised by resonance
      Raman spectroscopy. In degassed solution 1.+ disproportionates to give the
      dication 1(2+), whereas in aerated solutions the photodegradation product is the
      10-[4,5-di(methylsulfanyl) 1,3-dithiol-2-ylidene]anthracene-9(10 H)one (2). The
      dication 1(2+) has been characterised by a spectroelectrochemical study
      [lambdamax (CH2Cl2) = 377, 392, 419, 479 nm] and by an X-ray crystal structure of
      the salt 1(2-) (ClO4)2, which was obtained by electrocrystallisation. The planar
      anthracene and 1,3-dithiolium rings in the dication form a dihedral angle of 77.2
      degrees; this conformation is strikingly different from the saddle-shaped
      structure of neutral 1 reported previously.

PMID- 11303878
TI  - Dendritic biomimicry: microenvironmental hydrogen-bonding effects on tryptophan
      fluorescence.
AB  - Two series of dendritically modified tryptophan derivatives have been synthesised
      and their emission spectra measured in a range of different solvents. This paper
      presents the syntheses of these novel dendritic structures and discusses their
      emission spectra in terms of both solvent and dendritic effects. In the first
      series of dendrimers, the NH group of the indole ring is available for hydrogen
      bonding, whilst in the second series, the indole NH group has been converted to
      NMe. Direct comparison of the emission wavelengths of analogous NH and NMe
      derivatives indicates the importance of the Kamlet-Taft solvent beta3 parameter,
      which reflects the ability of the solvent to accept a hydrogen bond from the NH
      group, an effect not possible for the NMe series of dendrimers. For the NH
      dendrimers, the attachment of a dendritic shell to the tryptophan subunit leads
      to a red shift in emission wavelength. This dendritic effect only operates in non
      hydrogen-bonding solvents. For the NMe dendrimers, however, the attachment of a
      dendritic shell has no effect on the emission spectra of the indole ring. This
      proves the importance of hydrogen bonding between the branched shell and the
      indole NH group in causing the dendritic effect. This is the first time a
      dendritic effect has been unambiguously assigned to individual hydrogen-bonding
      interactions and indicates that such intramolecular interactions are important in
      dendrimers, just as they are in proteins. Furthermore, this paper sheds light on
      the use of tryptophan residues as a probe of the microenvironment within proteins
      -in particular, it stresses the importance of hydrogen bonds formed by the indole
      NH group.

PMID- 11303879
TI  - Synthesis and structural characterization of novel silenes stabilized by
      intramolecular coordination of a dialkylamino group.
AB  - Two intramolecularly donor-stabilized silenes, 1-(8-dimethylamino-1-naphthyl)
      1,2,2-tris(trimethylsilyl)silene (6a) and 1-(2-dimethylaminomethylphenyl)-1,2,2
      tris(trimethylsilyl)silene (6b), were synthesized according to a novel one-step
      process by the reaction of (dichloromethyl)tris(trimethylsilyl)silane (1) with a
      twofold molar excess of 8-dimethylamino-1-naphthyllithium or 2
      (dimethylaminomethyl)phenyllithium, respectively. Compounds 6a and 6b are
      thermally stable compounds. X-ray structural analyses of both silenes revealed
      strong donor-acceptor interactions between the dialkylamino groups and the
      electrophilic silene silicon atoms (Si-N distances: 6a: 1.751(3) A; 6b: 1.749(3)
      A) that lead to pyramidalization at the silicon centers. In contrast, the
      configuration at the silene carbon atoms was found to be planar. The Si=C
      distances (6a: 1.751(3) A; 6b: 1.749(3) A) fit with literature data of comparable
      compounds. Addition of water or methanol to the Si=C bonds of 6a,b afforded the
      silanols 7a,b and the methoxysilanes 8a,b, respectively. The compound 1-(8
      dimethylaminomethyl-1-naphthyl)-1,2,2-tris(trimethylsilyl)silene (6c), generated
      following the same procedure by the reaction of 1 with 8-(dimethylaminomethyl)-1
      naphthyllithium (molar ratio 1:2) proved to be unstable at room temperature and
      underwent rapid insertion of the Si=C group into a methylene C-H bond of the
      dimethylaminomethylnaphthyl ligand to afford the 1-silaacenaphthene 9.

PMID- 11303880
TI  - Quinone-annonaceous acetogenins: synthesis and complex I inhibition studies of a
      new class of natural product hybrids.
AB  - The natural product hybrids quinone-mucocin and quinone- squamocin D were
      synthesized. In these hybrids, the butenolide unit of the annonaceous acetogenins
      mucocin and squamocin D is exchanged for the quinone moiety of the natural
      complex I substrate ubiquinone. For both syntheses, a modular, highly convergent
      approach was applied. Quinone-mucocin was constructed out of a tetrahydropyran
      (THP) component 1, a tetrahydrofuran (THF) unit 2, and a quinone precursor 3. A
      stereoselective, organometallic coupling reaction was chosen for the addition of
      the THP unit to the rest of the molecule. In the final step, the oxidation to the
      free quinone was achieved by using cerium(IV) ammonium nitrate (CAN) as the
      oxidizing agent. Quinone-squamocin D was assembled in a similar manner, from the
      chiral side chain bromide 16, the central bis-THF core 17, and the quinone
      precursor 18. Inhibition of complex I (isolated from bovine heart mitochondria)
      by the quinone acetogenins and several smaller building blocks was examined;
      quinone mucocin and quinone-squamocin D act as strong inhibitors of complex I.
      These results and the data from the smaller substructures indicate that other
      substructures of the acetogenins besides the butenolide group, such as the
      polyether component and the lipophilic left-hand side chain, are necessary for
      the strong binding of the acetogenins to complex I.

PMID- 11303881
TI  - Labelled sigma receptor ligands: can their role in neurology and oncology be
      extended?

PMID- 11303882
TI  - A prototype high-resolution animal positron tomograph with avalanche photodiode
      arrays and LSO crystals.
AB  - To fully utilize positron emission tomography (PET) as a non-invasive tool for
      tissue characterization, dedicated instrumentation is being developed which is
      specially suited for imaging mice and rats. Semiconductor detectors, such as
      avalanche photodiodes (APDs), may offer an alternative to photomultiplier tubes
      for the readout of scintillation crystals. Since the scintillation
      characteristics of lutetium oxyorthosilicate (LSO) are well matched to APDs, the
      combination of LSO and APDs seems favourable, and the goal of this study was to
      build a positron tomograph with LSO-APD modules to prove the feasibility of such
      an approach. A prototype PET scanner based on APD readout of small, individual
      LSO crystals was developed for tracer studies in mice and rats. The tomograph
      consists of two sectors (86 mm distance), each comprising three LSO-APD modules,
      which can be rotated for the acquisition of complete projections. In each module,
      small LSO crystals (3.7 x 3.7 x 12 mm3) are individually coupled to one channel
      within matrices containing 2x8 square APDs (2.6 x 2.6 mm2 sensitive area per
      channel). The list-mode data are reconstructed with a penalized weighted least
      squares algorithm which includes the spatially dependent line spread function of
      the tomograph. Basic performance parameters were measured with phantoms and first
      experiments with rats and mice were conducted to introduce this methodology for
      biomedical imaging. The reconstructed field of view covers 68 mm, which is 80% of
      the total detector diameter. Image resolution was shown to be 2.4 mm within the
      whole reconstructed field of view. Using a lower energy threshold of 450 keV, the
      system sensitivity was 350 Hz/MBq for a line source in air in the centre of the
      field of view. In a water-filled cylinder of 4.6 cm diameter, the scatter
      fraction at the centre of the field of view was 16% (450 keV threshold). The
      count rate was linear up to 700 coincidence counts per second. In vivo studies of
      anaesthetized rats and mice showed the feasibility of in vivo imaging using this
      PET scanner. The first LSO-APD prototype tomograph has been successfully
      introduced for in vivo animal imaging. APD arrays in combination with LSO
      crystals offer new design possibilities for positron tomographs with finely
      granulated detector channels.

PMID- 11303883
TI  - Characterisation of fan-beam collimators.
AB  - Fan-beam collimators offer a good balance between resolution and noise. The
      collimator response may be included in iterative reconstruction algorithms in
      order to improve single-photon emission tomography (SPET) resolution. To this
      end, accurate determination of the focal region and characterisation of the
      collimator response as a function of the source co-ordinates must be performed.
      In this paper, a method to characterise fanbeam collimators is evaluated. First,
      we calculated the real focal region and the accuracy of the collimator
      convergence. Then, we confirmed the hypothesis that Gaussian distributions
      adequately fit the collimator responses, although no individualised treatment was
      performed for the tails of detector response which are associated with scattering
      and septal penetration. Finally, analytical functions were used to model the
      resolution and sensitivity. The parameter values in these functions were obtained
      from experimental measures by non-linear regression fitting. Our findings show
      differences of 1.43% between nominal and real focal length and standard
      deviations of 2.5 mm in the x-direction and 7.1 mm in the y-direction for the
      focal convergence. The correlation coefficients between experimental and
      predicted values were 0.994 for resolution and 0.991 for sensitivity. As a
      consequence, the proposed method can be used to characterise the collimator
      response.

PMID- 11303884
TI  - SPET of a computerised model of diffuse lung disease.
AB  - Emphysema is a common and debilitating disease that is the commonest cause of end
      stage respiratory failure. Treatment is either by lung transplantation or by lung
      volume reduction surgery (LVRS) that improves the biomechanics of respiration.
      Patient selection for LVRS hinges on the demonstration of heterogeneous disease,
      predominantly involving the upper lobes, as a good surgical outcome is most
      likely in these patients. We used a virtual model of lung scintigraphy to compare
      planar with tomographic scintigraphy for the detection of diffuse lung disease.
      Lesions of the magnitude of the lung acinus, as well as larger and smaller
      lesions, were distributed throughout the lungs in volumes from 2% to 50%. Single
      photon emission tomography does not add incremental value to planar images for
      the detection of diffuse lung disease.

PMID- 11303885
TI  - FDG-PET standardized uptake values in normal anatomical structures using
      iterative reconstruction segmented attenuation correction and filtered back
      projection.
AB  - Filtered back-projection (FBP) is the most commonly used reconstruction method
      for PET images, which are usually noisy. The iterative reconstruction segmented
      attenuation correction (IRSAC) algorithm improves image quality without reducing
      image resolution. The standardized uptake value (SUV) is the most clinically
      utilized quantitative parameter of [fluorine-18]fluoro-2-deoxy-D-glucose (FDG)
      accumulation. The objective of this study was to obtain a table of SUVs for
      several normal anatomical structures from both routinely used FBP and IRSAC
      reconstructed images and to compare the data obtained with both methods. Twenty
      whole-body PET scans performed in consecutive patients with proven or suspected
      non-small cell lung cancer were retrospectively analyzed. Images were processed
      using both IRSAC and FBP algorithms. Nonquantitative or gaussian filters were
      used to smooth the transmission scan when using FBP or IRSAC algorithms,
      respectively. A phantom study was performed to evaluate the effect of different
      filters on SUV. Maximum and average SUVs (SUVmax and SUVavg) were calculated in
      28 normal anatomical structures and in one pathological site. The phantom study
      showed that the use of a nonquantitative smoothing filter in the transmission
      scan results in a less accurate quantification and in a 20% underestimation of
      the actual measurement. Most anatomical structures were identified in all
      patients using the IRSAC images. On average, SUVavg and SUVmax measured on IRSAC
      images using a gaussian filter in the transmission scan were respectively 20% and
      8% higher than the SUVs calculated from conventional FBP images. Scatterplots of
      the data values showed an overall strong relationship between IRSAC and FBP SUVs.
      Individual scatterplots of each site demonstrated a weaker relationship for lower
      SUVs and for SUVmax than for higher SUVs and SUVavg. A set of reference values
      was obtained for SUVmax and SUVavg of normal anatomical structures, calculated
      with both IRSAC and FBP image reconstruction algorithms. The use of IRSAC and a
      gaussian filter for the transmission scan seems to give more accurate SUVs than
      are obtained from conventional FBP images using a nonquantitative filter for the
      transmission scan.

PMID- 11303886
TI  - Comparison of visual and ROI-based brain tumour grading using 18F-FDG PET: ROC
      analyses.
AB  - Several studies have suggested that the use of simple visual interpretation
      criteria for the investigation of brain tumours by positron emission tomography
      with fluorine-18 fluorodeoxyglucose (FDG-PET) might be similarly or even more
      accurate than quantitative or semi-quantitative approaches. We investigated this
      hypothesis by comparing the accuracy of FDG-PET brain tumour grading using a
      proposed six-step visual grading scale (VGS; applied by three independent
      observers unaware of the clinical history and the results of histopathology) and
      three different region of interest (ROI) ratios (maximal tumour uptake compared
      with contralateral tissue [Tu/Tis], grey matter [Tu/GM] and white matter
      [Tu/WM]). The patient population comprised 47 patients suffering from 17 benign
      (7 gliomas of grade II, 10 non-gliomatous tumours) and 30 malignant (23 gliomas
      of grade III-IV, 7 non-gliomatous tumours) tumours. The VGS results were highly
      correlated with the different ROI ratios (R=0.91 for Tu/GM, R=0.82 for Tu/WM, and
      R=0.79 for Tu/Tis), and high inter-observer agreement was achieved (kappa=0.63,
      0.76 and 0.81 for the three observers). The mean ROI ratios and VGS readings of
      gliomatous and non-gliomatous lesions were not significantly different. For all
      measures, high-grade lesions showed significantly higher FDG uptake than low
      grade lesions (P<0.005 to P<0.0001, depending on the measure used). Nominal
      logistic regressions and receiver operating characteristic (ROC) analyses were
      used to calculate cut-off values to differentiate low- from high-grade lesions.
      The predicted (by ROC) diagnostic sensitivity/specificity of the different tests
      (cut-off ratios shown in parentheses) were: Tu/GM: 0.87/0.85 (0.7), Tu/WM:
      0.93/0.80 (1.3). Tu/Tis: 0.80/0.80 (0.8) and VGS: 0.84/0.95 (uptake < GM, but >>
      WM). The VGS yielded the highest Az (+/-SE) value (i.e. area under the ROC curve
      as a measure of predicted accuracy), 0.97+/-0.03, which showed a strong tendency
      towards being significantly greater than the Az of Tu/Tis (0.88+/-0.06; P=0.06).
      Tu/GM (0.92+/-0.04) and Tu/WM (0.91+/-0.05) reached intermediate Az values (not
      significantly different from any other value). We conclude that the VGS
      represents a measure at least as accurate as the Tu/GM and Tu/WM ratios. The
      Tu/Tis ratio is less valid owing to the high dependence on the location of the
      lesion. Depending on the investigator's experience and the structure of the
      lesions, the easily used VGS might be the most favourable grading criterion.

PMID- 11303887
TI  - Decreased frontal serotonin 5-HT 2a receptor binding index in deliberate self
      harm patients.
AB  - Studies of serotonin metabolites in body fluids in attempted suicide patients and
      of post-mortem brain tissue of suicide victims have demonstrated the involvement
      of the serotonergic neurotransmission system in the pathogenesis of suicidal
      behaviour. Recently developed neuroimaging techniques offer the unique
      possibility of investigating in vivo the functional characteristics of this
      system. In this study the 5-HT2a receptor population of patients who had recently
      attempted suicide was studied by means of the highly specific radio-iodinated 5
      HT2a receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy) propyl]-4-methyl-4
      piperidinyl]-5-iodo-2-methoxybenzamide or 123I-5-I-R91150. Nine patients who had
      recently (1-7 days) attempted suicide and 12 age-matched healthy controls
      received an intravenous injection of 185 MBq 123I-5-I-R91150 and were scanned
      with high-resolution brain single-photon emission tomography (SPET). Stereotactic
      realigned images were analysed semi-quantitatively using predefined volumes of
      interest. Serotonin binding capacity was expressed as the ratio of specific to
      non-specific activity. The cerebellum was used as a measure of non-specific
      activity. An age-dependent 5-HT2a binding index was found, in agreement with
      previous literature. Deliberate self-harm patients had a significantly reduced
      mean frontal binding index after correction for age (P=0.002) when compared with
      controls. The reduction was more pronounced among deliberate self-injury patients
      (DSI) (P<0.001) than among deliberate self-poisoning patients (DSP). Frontal
      binding index was significantly lower in DSI patients than in DSP suicide
      attempters (P<0.001). It is concluded that brain SPET of the 5-HT2a serotonin
      receptor system in attempted suicide patients who are free of drugs influencing
      the serotonergic system shows in vivo evidence of a decreased frontal binding
      index of the 5-HT2a receptor, indicating a decrease in the number and/or in the
      binding affinity of 5-HT2a receptors.

PMID- 11303888
TI  - Differences in 99mTc-HMPAO brain SPET perfusion imaging between Tourette's
      syndrome and chronic tic disorder in children.
AB  - Early differential diagnosis between Tourette's syndrome and chronic tic disorder
      is difficult but important because both the outcome and the treatment of these
      two childhood-onset diseases are distinct. We assessed the sensitivity and
      specificity of brain single-photon emission tomography (SPET) perfusion imaging
      in distinguishing the two diseases, and characterized their different cerebral
      perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with
      chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain
      SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual
      interpretation and semiquantitative analysis of SPET images were performed. On
      visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had
      lesions characterized by decreased perfusion. The left hemisphere was more
      frequently involved. None of the children with chronic tic disorder had a visible
      abnormality. Semi-quantitative analysis showed that, compared with children with
      chronic tic disorder, children with Tourette's syndrome had significantly lower
      perfusion in the left lateral temporal area and asymmetric perfusion in the
      dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the
      visual approach, brain SPET perfusion imaging is sensitive and specific in
      differentiating Tourette's syndrome and chronic tic disorder. The perfusion
      difference between the two groups, demonstrated by semi-quantitative analysis,
      may be related more to the co-morbidity in Tourette's syndrome than to tics per
      se.

PMID- 11303889
TI  - Different uptake of 99mTc-ECD adn 99mTc-HMPAO in the same brains: analysis by
      statistical parametric mapping.
AB  - The purpose of this study was to investigate the differences between technetium
      99m ethyl cysteinate dimer (99mTc-ECD) and technetium-99m hexamethylpropylene
      amine oxime (99mTc-HMPAO) uptake in the same brains by means of statistical
      parametric mapping (SPM) analysis. We examined 20 patients (9 male, 11 female,
      mean age 62+/-12 years) using 99mTc-ECD and 99mTc-HMPAO single-photon emission
      tomography (SPET) and magnetic resonance imaging (MRI) of the brain less than 7
      days after onset of stroke. MRI showed no cortical infarctions. Infarctions in
      the pons (6 patients) and medulla (1), ischaemic periventricular white matter
      lesions (13) and lacunar infarction (7) were found on MRI. Split-dose and
      sequential SPET techniques were used for 99mTc-ECD and 99mTc-HMPAO brain SPET,
      without repositioning of the patient. All of the SPET images were spatially
      transformed to standard space, smoothed and globally normalized. The differences
      between the 99mTc-ECD and 99mTc-HMPAO SPET images were statistically analysed
      using statistical parametric mapping (SPM) 96 software. The difference between
      two groups was considered significant at a threshold of uncorrected P values less
      than 0.01. Visual analysis showed no hypoperfused areas on either 99mTc-ECD or
      99mTc-HMPAO SPET images. SPM analysis revealed significantly different uptake of
      99mTc-ECD and 99mTc-HMPAO in the same brains. On the 99mTc-ECD SPET images,
      relatively higher uptake was observed in the frontal, parietal and occipital
      lobes, in the left superior temporal lobe and in the superior region of the
      cerebellum. On the 99mTc-HMPAO SPET images, relatively higher uptake was observed
      in the medial temporal lobes, thalami, periventricular white matter and brain
      stem. These differences in uptake of the two tracers in the same brains on SPM
      analysis suggest that interpretation of cerebral perfusion is possible using SPET
      with 99mTc-ECD and 99mTc-HMPAO.

PMID- 11303890
TI  - Efficacy of high therapeutic doses of iodine-131 in patients with differentiated
      thyroid cancer and detectable serum thyroglobulin.
AB  - Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic
      disease after treatment of differentiated thyroid cancer. We evaluated the effect
      of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg
      during suppressive levothyroxine treatment (Tg-on), and in patients with a
      negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg
      off). Twenty-two patients with differentiated thyroid carcinoma underwent total
      thyroidectomy and radioiodine ablation. During the follow-up, six patients with
      detectable Tg-on and 16 patients with detectable Tg-off were identified. All
      patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131.
      Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was
      measured in 16 cases, 1 year after the administration of the blind therapeutic
      dose, at the time of the follow-up diagnostic scintigram. Six patients were
      followed up by Tg-on only. Post-therapy scintigrams revealed previously
      undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the
      remaining nine post-therapy scintigrams were negative. At the time of the blind
      therapeutic doses, Tg-off values ranged from 8 to 608 microg/l. After 1 year of
      follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were
      followed by Tg-on only (n=6), a decrease in Tg values was measured. It is
      concluded that blind therapeutic doses resulted in a decrease in Tg levels in the
      majority of patients with suspected recurrence or metastases. The post-treatment
      scintigrams revealed pathological uptake in 59% of patients.

PMID- 11303891
TI  - Outcome after radioiodine therapy in 107 patients with differentiated thyroid
      carcinoma and initial bone metastases: side-effects and influence of age.
AB  - Initial bone metastases in patients with differentiated thyroid carcinoma are
      rare, especially in younger patients. Long duration of therapy and high
      activities of radioiodine are often necessary to induce remission of metastatic
      disease. The curative potential of radioiodine therapy, in particular in younger
      patients, has not yet been determined. In this retrospective study we evaluated
      the therapeutic outcome, total radioiodine activities and associated side-effects
      in 107 patients with initial bone metastases. Eight of the 107 patients were
      younger than 45 (37.5+/-7.3) years, and were classified as group 1 (stage II,
      "low risk", WHO classification). The remaining 99 patients were older than 45
      (64.1+/-9.5) years, and formed group 2 (stage IV, "high risk", WHO
      classification). Total or partial remission was more frequently achieved in group
      1 than in group 2 (62.5% vs 49.5%). Lower activities were needed in group 1
      (18.89+/-15.08 GBq vs 41.97+/-31.25 GBq), and there were less marked alterations
      in the blood count in this group. In group 1, blood count alterations reached
      only grade I or II (WHO classification), whereas grade III and grade IV
      alterations as well as acute leukaemia were observed in group 2. In group 1,
      complete remission was achieved with radioiodine therapy (11.1 GBq) in three out
      of four patients with < or =3 bone metastases. Additional pulmonary metastases
      (present in 44 out of 107 patients) did not influence prognosis. We conclude that
      initial bone metastases in differentiated thyroid carcinoma can be treated with
      curative intent by means of radioiodine therapy, and that this approach has a
      particularly realistic chance of success in younger patients and those with a
      small number of metastases.

PMID- 11303892
TI  - 99mTc-MIBI scintigraphy of parathyroid adenomas and its relation to tumour size
      and oxyphil cell abundance.
AB  - The aim of this study was to assess the correlation between technetium-99m
      methoxyisobutylisonitrile (MIBI) uptake by parathyroid adenomas, oxyphil cell
      content and volume of the lesions. Thirty-one patients with parathyroid adenomas
      were evaluated prospectively. Preoperative double-phase 99mTc-MIBI scintigraphy
      was performed in all patients and tracer uptake by parathyroid lesions was
      assessed semi-quantitatively employing region of interest ratios to normal
      adjacent neck areas. Surgical specimens underwent histological evaluation and
      oxyphil cell content was determined. The intensity of tracer uptake was compared
      with oxyphil cell content, volume of the lesions and serum levels of calcium and
      parathormone. 99mTc-MIBI tracer uptake was correlated with oxyphil cell content,
      volume of parathyroid lesions and the functional status of the parathyroid
      adenomas. Tracer accumulation in oxyphil cells might partially explain the
      preferential 99mTc-MIBI retention in parathyroid lesions.

PMID- 11303894
TI  - Global and regional functional measurements with gated FDG PET in comparison with
      left ventriculography.
AB  - The purpose of this study was to validate the measurement of global and regional
      left ventricular cardiac function with ECG-gated fluorine-18 fluorodeoxyglucose
      (FDG) positron emission tomography (PET) by comparison with the corresponding
      indices from X-ray left ventriculography (LVG). Twenty-six patients (23 men, 3
      women, mean age 60.4 years) underwent LVG and ECG-gated (eight frames/cycle) FDG
      PET within an interval of 10.2+/-6.8 days. A volumetric sampling approach was
      used to obtain both global (EF: ejection fraction) and regional [%WT: relative
      regional count increase from end-diastolic (ED) to end-systolic (ES) phase]
      functional parameters. The gated PET parameters were compared with the
      corresponding findings of LVG in seven myocardial segments. EF(gated PET) and
      EF(LVG) did not differ significantly (30%+/-10% vs 32%+/-10%, P=NS). The two EF
      values correlated significantly, showing no significant systematic measurement
      bias [EF(gated PET) = 2.61+0.86 x EF(LVG), R=0.84, P<0.0001]. Inter- and intra
      observer reproducibility for EF were R=0.95, P<0.0001 and R=0.92, P<0.0001,
      respectively. Regional function was evaluated with LVG in 144 myocardial segments
      comprising 35 normokinetic, 70 hypokinetic and 39 a/dyskinetic segments. Visual
      analysis of LVG and gated PET correlated significantly (P<0.001), with an overall
      concordance ratio of 58% (83/144, kappa=0.35). Gated PET overestimated the
      regional function in 27% (39/144) and underestimated it in 15% (22/144). %WT
      showed significant differences between each pair of groups (a/dyskinesis, 13.2%+/
      9.3%; hypokinesis, 17.1%+/-8.8%; normokinesis, 21.8%+/-10.9%). Inter- and intra
      observer reproducibility was significant for %WT (R=0.77, P<0.0001 and R=0.79,
      P<0.0001, respectively). In conclusion, gated FDG PET permits assessment of
      global left ventricular cardiac function. In addition, assessment of regional
      function is feasible using the visual or the quantitative parameters.

PMID- 11303893
TI  - Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.
AB  - In a previous study, we showed the ability of technetium-99m
      methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in
      patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular,
      a semiquantitative score of the extension and intensity of bone marrow uptake was
      derived and correlated with both the clinical status of the disease and plasma
      cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI
      bone marrow uptake and to verify the intracellular localization of the tracer,
      bone marrow samples obtained from 24 multiple myeloma patients, three patients
      with monoclonal gammopathy of undetermined significance (MGUS) and two healthy
      donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque
      gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was
      expressed as the percentage of radioactivity specifically retained within the
      cells. The cellular localization of the tracer was assessed by micro
      autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a
      week of bone marrow sampling. Whole-body images were obtained 10 min after
      intravenous injection of 555 MBq of the tracer; the extension and intensity of
      99mTc-MIBI uptake were graded using the semiquantitative score. A statistically
      significant correlation was found between in vitro uptake of 99mTc-MIBI and both
      plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001)
      and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No
      specific tracer uptake was found in bone marrow samples obtained from the two
      healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside
      the plasma cells infiltrating the bone marrow. Therefore, our findings show that
      the degree of tracer uptake both in vitro and in vivo is related to the
      percentage of infiltrating plasma cells which accumulate the tracer in their
      inner compartments.

PMID- 11303895
TI  - Assessment of the effect of revascularization early after CABG using ECG-gated
      perfusion single-photon emission tomography.
AB  - When an arterial graft is used, reversible perfusion defects on single-photon
      emission tomography (SPET) perfusion images are occasionally observed early after
      coronary artery bypass graft surgery (CABG), owing to the restricted flow
      capacity. The purpose of this study was to determine whether the functional
      information obtained with electrocardiography (ECG)-gated perfusion SPET could be
      helpful in evaluating the effect of revascularization early after CABG. Twenty
      three patients (18 men and 5 women, mean age 65+/-9 years) underwent stress/re
      injection thallium-201 ECG-gated SPET before and 4 weeks after CABG (13 with
      exercise and 10 with dipyridamole). Patency of all grafts was confirmed by
      coronary angiography 1 month after CABG. Cardiac functional data including the
      left ventricular ejection fraction (LVEF) and the transient ischaemic dilatation
      (TID) ratio were analysed using a commercially available automated program. The
      conventional stress and re-injection tomograms were interpreted by means of a
      five-point scoring system in a nine-segment model. Stress-induced reversible
      201Tl perfusion defects were present in 64% of the myocardial segments bypassed
      by patent arterial grafts, in contrast to 42% of the myocardial segments bypassed
      by patent venous grafts (chi2=7.8, P=0.005). Of the 23 patients, 12 showed
      improvement in summed ischaemic scores (group 1), while 11 had no change or
      deterioration (group 2), although all grafts were patent on postoperative
      catheterization. The TID ratio improved in both group 1 and group 2 before and
      after CABG (1.14+/-0.13 vs 0.99+/-0.07, P=0.001 and 1.09+/-0.07 vs 0.94+/-0.05,
      P=0.002, respectively). However, LVEF did not significantly improve in group 1 or
      group 2 after CABG (42.5%+/-9.9% vs 47.5%+/-11.8%, and 52.1%+/-7.5% vs 53.1%+/
      5.9%, respectively). Perfusion imaging or LVEF assessment is of limited value
      early after CABG. The TID ratio obtained with ECG-gated perfusion SPET may be a
      useful marker to evaluate the effect of revascularization early after surgery.

PMID- 11303896
TI  - Imaging infection/inflammation in the new millennium.
AB  - In the closing half of the past century a wide variety of approaches were
      developed to visualise infection and inflammation by gamma scintigraphy. Use of
      autologous leucocytes, labelled with indium-111 or technetium-99m, is still
      considered the "gold standard" nuclear medicine technique for the imaging of
      infection and inflammation. However, the range of radiopharmaceuticals used to
      investigate infectious and non-microbial inflammatory disorders is expanding
      rapidly. Developments in protein/peptide chemistry and in radiochemistry should
      lead to agents with very high specific activities. Recently, positron emission
      tomography with fluorine-18 fluorodeoxyglucose has been shown to delineate
      infectious and inflammatory foci with high sensitivity. The third millennium will
      witness a gradual shift from basic (non-specific) or cumbersome, even hazardous
      techniques (radiolabelled leucocytes) to more sophisticated approaches. Here a
      survey is presented of the different approaches in use or under investigation.

PMID- 11303897
TI  - Nuclear medicine in tropical diseases.

PMID- 11303898
TI  - Arm positioning in thallium-201 cardiac imaging.

PMID- 11303899
TI  - Current concepts concerning orbital radiotherapy in patients with thyroid eye
      disease.

PMID- 11303900
TI  - European system for reporting adverse reactions to and defects in
      radiopharmaceuticals: annual report 1999.

PMID- 11303901
TI  - Update of the EBNM syllabus for post-graduate specialisation in nuclear medicine
      (Syllabus Update 2000). The Syllabus Committee of the European Board of Nuclear
      Medicine UEMS Specialist Section of Nuclear Medicine.

PMID- 11303902
TI  - In vivo morphometry and functional analysis of human articular cartilage with
      quantitative magnetic resonance imaging--from image to data, from data to theory.
AB  - Analyses of form-function relationships and disease processes in human articular
      cartilage necessitate in vivo assessment of cartilage morphology and
      deformational behavior. MR imaging and advanced digital post-processing
      techniques have opened novel possibilities for quantitative analysis of cartilage
      morphology, structure, and function in health and disease. This article reviews
      work on three-dimensional post-processing of MR image data of articular
      cartilage, summarizing studies on the accuracy and precision of quantitative
      analyses in human joints. It presents normative values on cartilage volume,
      thickness, and joint surface areas in the human knee, and describes the
      correlation between different joints and joint surfaces as well as their
      association with gender, body dimensions, and age. The article summarizes ongoing
      work on functional adaptation of articular cartilage to mechanical loading,
      analyses of in situ cartilage deformation in intact joints in vivo and in vitro,
      and the quantitative evaluation of cartilage tissue loss in osteoarthritis. We
      describe evolving techniques for assessment of the structural/biochemical
      composition of articular cartilage, and discuss future perspectives of
      quantitative cartilage imaging in the context of joint mechanics, mechano
      adaptation, epidemiology, and osteoarthritis research. Specifically, we show that
      fat-suppressed gradient echo sequences permit valid analysis of cartilage
      morphology, both in healthy and severely osteoarthritic joints, as well as highly
      reproducible measurements (CV%=1 to 3% in the knee, and 2 to 10% in the ankle).
      Relatively small differences in cartilage morphology exist between both limbs of
      the same person (approximately 5%), but large differences between individuals
      (CV% approximately 20%). Men display only slightly thicker cartilage then women
      (approximately 10%), but significantly larger joint surface areas (approximately
      25%), even when accounting for differences in body weight and height. Weight and
      height represent relatively poor predictors of cartilage thickness (r2 <15%), but
      muscle cross section areas display more promising correlations (r2 >40%). The
      level of physical exercise (sportive activity) does not account for
      interindividual differences in cartilage thickness. The thickness appears to
      decrease slightly in the elderly--in particular in women, even in the absence of
      osteoarthritic cartilage lesions. Strenuous physical exercises (e.g., knee bends)
      cause a 6% patellar cartilage deformation in young individuals, but significantly
      less deformation in elderly men and women (<3%). The time required for full
      recovery after exercise (fluid flow back into the matrix) is relatively long
      (approximately 90 min). Static in situ compression of femoropatellar cartilage
      with 150% body weight produces large deformations after 4 h (approximately 30%
      volume change), but only very little deformation during the first minutes of
      loading. Quantitative analyses of magnetization transfer and proton density hold
      promise for biochemical evaluation of articular cartilage, and are shown to be
      related to the deformational behavior of the cartilage. Application of these
      techniques to larger cohorts of patients in epidemiological and clinical studies
      will establish the role of quantitative cartilage imaging not only in basic
      research on form-function relationships of articular cartilage, but also in
      clinical research and management of osteoarthritis.

PMID- 11303903
TI  - Expression of PTHrP and PTHR (PTH/PTHrP-r) mRNAs and polypeptides in bovine ovary
      and stimulation of bovine blastocyst development in vitro following PTHrP
      treatment during oocyte maturation.
AB  - Parathyroid hormone related protein (PTHrP) and its receptor have well
      established roles in the development and regulation of many tissues, including
      bone and mammary gland. The objectives of this study were: (1) to characterize
      the distribution of mRNAs encoding parathyroid hormone (PTH)-related protein
      (PTHrP) and receptor (PTHR) in bovine ovary; (2) to characterize the distribution
      of PTHrP and PTHR polypeptides in bovine ovary; (3) to examine the influences of
      PTHrP (1-141) treatment during bovine oocyte maturation in vitro on blastocyst
      development. mRNAs encoding PTHrP and PTHR were detected by in situ hybridization
      methods in oocytes, and granulosa cells in all follicles from primordial to large
      antral. PTHrP and PTHR polypeptides displayed distinct distribution patterns with
      PTHrP polypeptides primarily confined to oocytes from primordial to large antral
      follicles. PTHrP polypeptides were detectable but at a reduced level in ovarian
      stroma and in granulosa and thecal layers. PTHR polypeptides were detected in
      oocytes of all follicular stages but were predominantly found in ovarian stroma,
      granulosa and theca follicular layers. Supplementation of serum-free cSOFMaa
      oocyte maturation medium with PTHrP (1-141) resulted in a concentration-dependent
      increase in development to the blastocyst stage in vitro. The results suggest
      that granulosa cells may be a primary site of PTHrP production and release.
      Oocytes from all follicular stages stained strongly for PTHrP polypeptides and
      PTHrP enhanced development to the blastocyst stage in vitro.

PMID- 11303904
TI  - Frizzled 2 is transiently expressed in neural crest-containing areas during
      development of the heart and great arteries in the mouse.
AB  - Frizzled 2 acts as a 7-transmembrane receptor in the Wnt-Dishevelled signal
      transduction cascade. Among others, this cascade has been associated with neural
      crest cell proliferation and early migration during development in mammals. The
      genes for some components of this cascade are located in chromosomal regions that
      are deleted in human syndromes associated with neural crest cell defects, like
      DiGeorge and Velo-Cardio-Facial Syndrome. These syndromes are often accompanied
      by abnormalities in cardiac morphology. Furthermore, we have reported in previous
      studies the upregulation of the tissue polarity gene frizzled 2 in myofibroblasts
      during their migration into the necrotic area after myocardial infarction in the
      adult heart. It is known that genes that are upregulated during cardiac
      remodeling due to pathology often play a role during development. To investigate
      whether frizzled 2 can be associated with the process of cardiac morphogenesis we
      studied its expression in the thoracic arterial system and heart of mouse
      embryo's of 10, 12, 14, 16 and 18 days after conception by means of in situ
      hybridization. At day 10 after conception signal could be found in the pharyngeal
      arches and arch arteries. The outflow tract, the ascending aorta and the
      pulmonary trunk were positive for frizzled 2 from day 12 on. This expression
      decreased with time and at day 18 only some signal could be detected in the aorta
      and pulmonary trunk. In contrast, in coronary and pulmonary arteries no
      expression was observed at any time point. Minor myocardial expression was
      observed in the ventricular septum at days 12 and 14. Atrial expression, although
      considerably lower than ventricular expression, could be detected somewhat later
      at days 14 and 16. Our results indicate that there is transient expression of
      frizzled 2 in areas that are invested by neural crest cells. This expression is
      downregulated upon neural crest cell differentiation. The frizzled 2 expression
      supports a role for the Wnt-frizzled pathway in neural crest-related disorders.

PMID- 11303905
TI  - Differential expression and regulation of the PKA signalling pathway in fast and
      slow skeletal muscle.
AB  - To identify intracellular signalling pathways that transduce muscle electrical
      activity, we have investigated the Protein Kinase A (PKA) pathway in fast and
      slow skeletal muscle. The slow soleus muscle (SOL) displayed approximately twice
      as much PKA catalytic activity and cAMP-binding compared to the fast Extensor
      Digitorum Longus (EDL) muscle. These results were confirmed by Western blot
      analysis using antibodies directed against the catalytic or regulatory subunits
      of PKA. PKA subunits were concentrated at the neuromuscular junction in
      innervated and denervated muscle fibers demonstrating that PKA is expressed post
      synaptically. In addition, we also detected PKA subunits outside the junctional
      area, suggesting that PKA functions outside of the synaptic regions. Following
      denervation, levels of cyclic AMP, PKA C activity, R cAMP-binding and RI alpha
      protein levels increased significantly in the SOL, in contrast to the EDL where
      only elevated levels of RI alpha protein were observed. These observations
      demonstrate that PKA levels in skeletal muscle are subject to control at several
      levels and suggest that some of the differences may be in the pattern of
      electrical activity that motoneurons impose on the SOL and EDL.

PMID- 11303906
TI  - Atypical features of  rat dentate granule cells: recurrent basal dendrites and
      apical axons.
AB  - The stereotyped morphology of dentate granule cells in rodents consists of apical
      dendrites arborizing in the molecular layer and an axon arising from the opposite
      pole of the soma. Recently, we showed that epilepsy induces the formation of
      basal dendrites on granule cells and that these dendrites extend into the hilus
      of the dentate gyrus. The present Golgi study of granule cells from adult rats
      shows two atypical features for granule cells in control rats. One is the
      occurrence of recurrent basal dendrites (RBDs) that are defined as basal
      dendrites arising at or near the hilar pole of the soma and then curving back to
      the molecular layer. The frequency of granule cells with RBDs was 3.8% in control
      rats. The second is apical axons of granule cells that were observed to originate
      from either the apical pole of the soma or an apical dendrite. The incidence of
      these "apical" axons was about 1%. These morphological findings in the present
      study suggest that rat granule cells are more heterogeneous than previously
      indicated. Furthermore, their frequency was not increased in epileptic rats.

PMID- 11303907
TI  - Anatomy and development of the koala, Phascolarctos cinereus: an evolutionary
      perspective on the superfamily Vombatoidea.
AB  - Fifteen koalas (Phascolarctos cinereus)--5 pouched young from 4 to 6.5 months and
      10 adults from 5 to 16.5 years--were analyzed for functional parameters (body
      composition, limb segment and muscle mass, post-cranial skeletal characters) and
      developmental expressions (growth of body, brain, musculature). These data were
      compared with a convergent eutherian, the three-toed sloth, Bradypus infuscatus,
      and with the koala's distant (Macropodid; wallabies) and proximate (Vombatid;
      wombats) marsupial relatives. Musculoskeletal structures correlated with sitting
      and climbing; the growth of the young and the physiological demands of adulthood
      correlated with the low-quality diet of Eucalyptus foliage. The gestalt of the
      ancestral Vombatoids (pronograde quadrupeds, generalist browsers and social
      conservatives with low basal metabolism and attenuated development) provided the
      baseline essential for their locomotor and nutritional divergence into arboreal
      browsers, the koalas, and fossorial grazers, the wombats.

PMID- 11303908
TI  - The molecular control of DNA damage-induced cell death.
AB  - Because of the singular importance of DNA for genetic inheritance, all organisms
      have evolved mechanisms to recognize and respond to DNA damage. In metazoans,
      cells can respond to DNA damage either by undergoing cell cycle arrest, to
      facilitate DNA repair, or by undergoing cell suicide. Cell death can either occur
      by activation of the apoptotic machinery or simply be a consequence of
      irreparable damage that prevents further cell division. In germ cells, mechanisms
      for limiting alterations to the genome are required for faithful propagation of
      the species whereas in somatic cells, responses to DNA damage prevent the
      accumulation of mutations that might lead to aberrant cell proliferation or
      behavior. Several of the genes that regulate cellular responses to DNA damage
      function as tumor suppressors. The clinical use of DNA damaging agents in the
      treatment of cancer can activate these tumor suppressors and exploits the
      cellular suicide and growth arrest mechanisms that they regulate. It appears that
      in some but not all types of tumors the propensity to undergo apoptosis is a
      critical determinant of their sensitivity to anti-cancer therapy. This review
      describes current understanding of the molecular control of DNA damage-induced
      apoptosis with particular attention to its role in tumor suppression and cancer
      therapy.

PMID- 11303909
TI  - Protection of apoptotic cell death by protein A.
AB  - The word "Apoptosis" or pragrammed cell death is described as the ultimate end of
      multiple cellular events converging from numerous initiating events to the
      ultimate death of a cell or organism. Several processes, such as initiation of
      death signals at the plasma membrane, expression of pro-apoptotic oncoproteins,
      activation of death proteases, endonucleases etc., that ultimately coalesce to a
      common irreversible execution phase, lead to cell demise. Counteracting the death
      signals are cell survival factors. A balance between the cell death and cell
      survival factors plays a major role in the decision making process as to whether
      a cell should die or must live. It is, therefore, hypothesized that if the
      balance can be shifted in favor of cell survival, one might be able to arrest the
      aging process, save the injured cells or else if the balance is shifted toward
      cell-kill it might help destroy tumors and other undesirable cells. Protein A
      (PA) of Staphylococcus aureus has been found to have multifarious biological
      response modifying properties. It has been shown to possess anti-tumor,
      antitoxic, anti-parasitic and antifungal activities. It also acts as a potent
      immunostimulator. PA can protect bone marrow progenitor cells from zidovudin(AZT)
      induced apoptosis and can stimulate immunocyte proliferation, thereby helping to
      replenish/restore the depleted hematopoietic cell pool. Such ability to replenish
      hematopoietic cells is a common property of PA observed against a number of toxic
      drugs/chemicals, such as cyclophosphamide, benzene, aflatoxin, salmonella
      endotoxin, etc. Interestingly, it was further demonstrated in our laboratory that
      PA can selectively kill tumor cells without affecting normal cells of the host. A
      search for the mechanisms of PA action revealed that this bacterial protein could
      shift the balance between pro- and anti-apoptotic proteins in favor of survival
      in normal cells, but in favor of cell death in tumor cells at a particular dose
      level. This unique property of PA suggests that controlled use of such type of
      Biological Response Modifier might help in controlling both cell growth and death
      phenomena.

PMID- 11303910
TI  - Ethanol-induced apoptotic neurodegeneration in the developing brain.
AB  - It has been known for three decades that ethanol, the most widely abused drug in
      the world, has deleterious effects on the developing human brain, but progress
      has been slow in developing animal models for studying this problem, and the
      underlying mechanisms have remained elusive. Recently, we have shown that during
      the synaptogenesis period, also known as the brain growth spurt period, ethanol
      has the potential to trigger massive neuronal suicide in the in vivo mammalian
      brain. The brain growth spurt period in humans spans the last trimester of
      pregnancy and first several years after birth. The NMDA antagonist and
      GABAmimetic properties of ethanol may be responsible for its apoptogenic action,
      in that other drugs with either NMDA antagonist or GABAmimetic actions also
      trigger apoptotic neurodegeneration in the developing brain. Our findings provide
      a likely explanation for the reduced brain mass and neurobehavioral disturbances
      associated with the human fetal alcohol syndrome. Furthermore, since NMDA
      antagonist and GABAmimetic drugs are sometimes abused by pregnant women and also
      are used as anticonvulsants, sedatives or anesthetics in pediatric medicine, our
      findings raise several complex drug safety issues. In addition, the observation
      that ethanol and several other drugs trigger massive neuronal apoptosis in the
      developing brain provides an unprecedented opportunity to study both
      neuropathological aspects and molecular mechanisms of apoptotic neurodegeneration
      in the in vivo mammalian brain.

PMID- 11303911
TI  - ATM dependent apoptosis in the nervous system.
AB  - Ataxia-telangiectasia is a human syndrome resulting from mutations of the ATM
      protein kinase that is characterized by radiation sensitivity and
      neurodegeneration. Although neuroprotective, the molecular details of ATM
      function in the nervous system are uncertain. However, in the mouse, Atm is
      essential for ionizing radiation-induced apoptosis in select postmitotic
      populations of the developing nervous system. Atm-dependent apoptosis in the
      nervous system also requires p53, consistent with the well-established link of
      p53 as a major substrate of ATM. Furthermore, the proapoptotic effector Bax is
      also required for most, but not all, Atm-dependent apoptosis. Therefore, after
      DNA damage in the developing nervous system, Atm initiates a p53-dependent
      apoptotic cascade in differentiating neural cells. Together, these data suggest
      ATM-dependent apoptosis may be important for elimination of neural cells that
      have accumulated genomic damage during development, thus preventing dysfunction
      of these cells later in life.

PMID- 11303912
TI  - GnRH-Bik/Bax/Bak chimeric proteins target and kill adenocarcinoma cells; the
      general use of pro-apoptotic proteins of the Bcl-2 family as novel killing
      components of targeting chimeric proteins.
AB  - In recent years chimeric proteins carrying bacterial toxins as their killing
      moiety, have been developed to selectively recognize and kill cell populations
      expressing speciific receptors. The involvement of Gonadotropin releasing hormone
      (GnRH) has been demonstrated in several adenocarcinomas and a GnRH-bacterial
      toxin chimeric protein (GnRH-PE66) was thus developed and found to specifically
      target and kill adenocarcinoma cells both in vitro and in vivo. Because of the
      immunogenicity and the non-specific toxicity of the bacterial toxins, we have
      developed new chimeric proteins, introducing apoptosis inducing proteins of the
      Bcl-2 family as novel killing components. Sequences encoding the human Bik, Bak
      or Bax proteins were fused to the GnRH coding sequence at the DNA level and were
      expressed in E. coli. GnRH-Bik, GnRH-Bak and GnRH-Bax new chimeric proteins
      efficiently and specifically inhibited the cell growth of adenocarcinoma cell
      lines and eventually led to cell death. All three Bcl2-proteins-based chimeric
      proteins seem to induce apoptosis within the target cells, without any additional
      cell death stimulus. Apoptosis-inducing-proteins of the Bcl-2 family targeted by
      the GnRH are novel potential therapeutic reagents for adenocarcinoma treatment in
      humans. This novel approach could be widely applied, using any molecule that
      binds a specific cell type, fused to an apoptosis-inducing protein.

PMID- 11303913
TI  - CDK inhibitors suppress apoptosis induced by chemicals and by excessive
      expression of a cell death gene, reaper, in Drosophila cells.
AB  - The present study was aimed to investigate whether or not cyclin-dependent
      kinases (CDKs) participate in different cascades leading to apoptosis. We
      examined the effects of two CDK inhibitors, olomoucine (OLM) and butyrolactone-I
      (BL-I), on apoptosis induced in two kinds of Drosophila cell lines. Increases of
      caspase activity induced by actinomycin D, cycloheximide, H-7 or A23187 in a
      Drosophila neuronal cell line, ML-DmBG2-c2, and induced by excessive expression
      of a Drosophila cell death gene, reaper, in Drosophila S2 cells were suppressed
      by 24-h pretreatment of each CDK inhibitor. Concomitant with the suppression of
      the caspase activity, fragmentations of cells and DNA, representatives of
      apoptosis, were also inhibited. These results suggest that CDK(s) participates in
      progression of apoptosis. However, these effects of the CDK inhibitors were also
      observed even at lower doses which did not affect cell proliferation. Therefore,
      it was shown that apoptosis is not always related to cell cycle in Drosophila
      cells. It was also suggested that the target(s) of the CDK inhibitors locates
      upstream of caspase in the cascade(s) of apoptosis.

PMID- 11303914
TI  - Early transitory rise in intracellular pH leads to Bax conformation change during
      ceramide-induced apoptosis.
AB  - Ceramide can induce apoptosis through a caspase independent pathway. Bax has been
      described as able to kill cells in the absence of caspase activity, therefore we
      measured Bax in situ during ceramide-induced apoptosis using anti-Bax antibodies
      and flow cytometry analysis. An early (<30 min) increase in Bax labeling was
      observed after the addition of several ceramide species to several hemopoietic
      related cell types. On U937, this increase was not due to antigens synthesis or
      processing, but rather an increased accessibility or reactivity of Bax antigens
      for antibodies. This increased immuno-reactivity of Bax was not inhibited by Z
      VAD-fmk nor leupeptin, and preceded nuclear fragmentation by several hours. Such
      an increase in immuno-reactivity was also observed after Fas ligation, but it
      occurred later (>2 h) accompanying nuclear apoptosis, and was inhibited by Z-VAD
      fmk. Bax immuno-reactivity was found to be related to intracellular pH (pHi), and
      C2-Ceramide (C2-Cer) induced a very early (<10 min) transitory increase in pHi.
      Both Bax immunoreactivity and pHi increases were dependent on the mitochondrial
      permeability transition pore (PTP) status. It was concluded from these results
      that C2-Cer induced a transitory increase in pHi in relation to the PTP. This
      rise in pHi led to conformational changes in Bax which could be responsible for
      further apoptosis in the C2-Cer pathway while it was a consequence of caspase
      activation in the Fas pathway.

PMID- 11303915
TI  - Prediction models for sound leakage through noise barriers.
AB  - Two numerical models are presented for the prediction of sound leakage through
      openings in thin hard barriers. The first numerical method is based on a simple
      procedure of numerical integration that can be implemented straightforwardly.
      This model is a more general approach, suitable for barriers with arbitrary gaps.
      The second model is a new method that permits prediction of sound leakage due to
      the presence of horizontal gaps in a long barrier. In the new method, effective
      barriers of appropriate heights represent the edges of the horizontal gaps. The
      sound diffracted by each effective barrier is calculated by a closed-form
      analytic expression. The total sound-pressure level is determined from a sum of
      these diffracted fields. Hence, the new method is fast, simple, and intuitive,
      allowing the leakage to be assessed accurately. The validity of these two
      numerical models is confirmed by precise experimental measurements.

PMID- 11303917
TI  - Relation of acoustical parameters with and without audiences in concert halls and
      a simple method for simulating the occupied state.
AB  - Five acoustical parameters-reverberation time RT, early decay time EDT, clarity
      C80, strength G, and interaural cross-correlation coefficient IACC-were measured
      using identical procedures with and without audiences in six concert and opera
      halls. Reverberation times without audiences were measured in 15 additional halls
      using the same measuring techniques as for the six halls above, but for full
      occupancy the data were taken from musical stop chords at symphonic concerts.
      This paper shows that in all halls (1) the occupied RT can be predicted from the
      unoccupied RT using a linear regression equation, y = a - b exp(x), within
      acceptable limits, at low- and mid-frequencies. It is also shown for the six
      halls that (2) occupied C80's are predicted accurately from unoccupied values by
      the newly proposed equation; (3) G's with and without audiences are highly
      correlated by a first degree linear regression equation; and (4) IACCs have
      nearly the same value in both occupied and unoccupied halls. As a separate
      subject, the successful use of a cloth covering for seats in a concert or opera
      hall to simulate the occupied condition has been developed.

PMID- 11303916
TI  - Community noise exposure and stress in children.
AB  - Although accumulating evidence over the past two decades points towards noise as
      an ambient stressor for children, all of the data emanate from studies in high
      intensity, noise impact zones around airports or major roads. Extremely little is
      known about the nonauditory consequences of typical, day-to-day noise exposure
      among young children. The present study examined multimethodological indices of
      stress among children living under 50 dB or above 60 dB (A-weighted, day-night
      average sound levels) in small towns and villages in Austria. The major noise
      sources were local road and rail traffic. The two samples were comparable in
      parental education, housing characteristics, family size, marital status, and
      body mass index, and index of body fat. All of the children were prescreened for
      normal hearing acuity. Children in the noisier areas had elevated resting
      systolic blood pressure and 8-h, overnight urinary cortisol. The children from
      noisier neighborhoods also evidenced elevated heart rate reactivity to a discrete
      stressor (reading test) in the laboratory and rated themselves higher in
      perceived stress symptoms on a standardized index. Furthermore girls, but not
      boys, evidenced diminished motivation in a standardized behavioral protocol. All
      data except for the overnight urinary neuroendocrine indices were collected in
      the laboratory. The results are discussed in the context of prior airport noise
      and nonauditory health studies. More behavioral and health research is needed on
      children with typical, day-to-day noise exposure.

PMID- 11303918
TI  - Simulation of jet-noise excitation in an acoustic progressive wave tube facility.
AB  - Acoustic excitation produced by jet-engine effluxes was simulated in a
      progressive wave tube (APWT) facility with a computer-based control system. The
      APWT siren is driven by a signal generated numerically in a PC and then converted
      into analog form. Characteristics of the acoustic pressure measured by a
      microphone are analyzed in digital form and compared with those prescribed for
      simulation. Divergence is compensated by immediate modification of the driving
      signal and this action is repeated in the form of iterative process until the
      test specification is attained. Typical power spectral density (PSD) shapes with
      maxima at low and high frequencies were simulated. A "tailoring" approach has
      been also achieved when a test specification was determined directly from field
      measurements for the particular aircraft under consideration. Since acoustic
      pressure signals of high level differ from the Gaussian random process model,
      particularly in terms of asymmetric probability density function, a method has
      been developed to make the driving signal also non-Gaussian by simulating
      skewness and kurtosis parameters of the APWT acoustic excitation simultaneously
      with PSD control. Experimental results with Gaussian and non-Gaussian
      characteristics obtained for various PSD specifications including sharp and
      narrow peaks are presented in the paper.

PMID- 11303919
TI  - Underwater source detection using a spatial stationarity test.
AB  - The problem of detecting a source in shallow water is addressed. The complexity
      of such a propagation channel makes precise modeling practically impossible. This
      lack of accuracy causes a deterioration in the performance of the optimal
      detector and motivates the search for suboptimal detectors which are insensitive
      to uncertainties in the propagation model. A novel, robust detector which
      measures the degree of spatial stationarity of a received field is presented. It
      exploits the fact that a signal propagating in a bounded channel induces spatial
      nonstationarity to a higher degree than mere background noise. The performance of
      the proposed detector is evaluated using both simulated data and experimental
      data collected in the Mediterranean Sea. This performance is compared to those of
      three other detectors, employing different extents of prior information. It is
      shown that when the propagation channel is not completely known, as is the case
      of the experimental data, the novel detector outperforms the others in terms of
      threshold signal-to-noise ratio (SNR). In the presence of environmental mismatch,
      the threshold SNR of the novel detector for the experimental data appears 2-5 dB
      lower than the other detectors. That is, this detector couples good performance
      with robustness to propagation uncertainties.

PMID- 11303920
TI  - Feature dependence in the automatic identification of musical woodwind
      instruments.
AB  - The automatic identification of musical instruments is a relatively unexplored
      and potentially very important field for its promise to free humans from time
      consuming searches on the Internet and indexing of audio material. Speaker
      identification techniques have been used in this paper to determine the
      properties (features) which are most effective in identifying a statistically
      significant number of sounds representing four classes of musical instruments
      (oboe, sax, clarinet, flute) excerpted from actual performances. Features
      examined include cepstral coefficients, constant-Q coefficients, spectral
      centroid, autocorrelation coefficients, and moments of the time wave. The number
      of these coefficients was varied, and in the case of cepstral coefficients, ten
      coefficients were sufficient for identification. Correct identifications of 79%
      84% were obtained with cepstral coefficients, bin-to-bin differences of the
      constant-Q coefficients, and autocorrelation coefficients; the latter have not
      been used previously in either speaker or instrument identification work. These
      results depended on the training sounds chosen and the number of clusters used in
      the calculation. Comparison to a human perception experiment with sounds produced
      by the same instruments indicates that, under these conditions, computers do as
      well as humans in identifying woodwind instruments.

PMID- 11303921
TI  - The feasibility of maximum length sequences to reduce acquisition time of the
      middle latency response.
AB  - Maximum length sequences (MLS) have been used to improve the signal-to-noise
      ratio (SNR) of otoacoustic emissions [Thornton, J. Acoust. Soc. Am. 94, 132-136
      (1993)] and the auditory brainstem response [Thornton and Slaven, Br. J. Audiol.
      27, 205-210 (1993)]. By implication, a shorter recording time would be required
      to give equal signal-to-noise ratio (SNR). This study aimed to establish whether
      it is also possible to improve the SNR of the auditory-evoked potential termed
      the middle latency response (MLR) using maximum length sequences (MLS).
      Recordings of 180 s each were made using a conventional recording rate and MLS
      rates of 42, 89, and 185 clicks/s. Three different stimulus intensities were used
      in the range 30 to 70 dB nHL. The rate of 89 clicks/s was found to produce most
      improvement in SNR for both the Na-Pa region of the MLR and the Na-Pb region.
      This improvement in SNR using MLS implies that an MLS rate of 89 clicks/s would
      produce a fourfold reduction in recording time for equal SNR over conventional
      recording for the Pa-Nb region of the MLR at a stimulus intensity of 70 dB nHL.
      The latency of the Nb wave was found to reduce significantly using MLS. An MLR
      could not be recorded from every subject in this study, but more subjects had an
      identifiable response for MLS than for conventional recordings. Use of MLS to
      record the MLR appears to offer the potential for reduction in test time and
      better wave identification.

PMID- 11303922
TI  - Searching for the time constant of neural pitch extraction.
AB  - Multichannel, auditory models have been repeatedly used to explain many aspects
      of human pitch perception. Among the most successful ones are models where pitch
      is estimated based on an analysis of periodicity in the simulated auditory-nerve
      firing. This periodicity analysis is typically implemented as a running
      autocorrelation, i.e., the autocorrelation is calculated within a temporal window
      which is shifted along the time axis. The window was suggested to have an
      exponential decay with time-constant estimates between 1.5 and 100 ms. The window
      length determines the minimal integration time of pitch extraction. The present
      experiments are designed to quantify the temporal window of pitch extraction
      using regular-interval noises (RINs). RINs were generated by concatenating equal
      duration noise samples which produce a pitch corresponding to the reciprocal of
      the sample duration when the samples are identical (periodic noise). When the
      samples are independent, the stimulus is Gaussian noise and produces no pitch.
      Using RIN stimuli where periodic portions interchange with aperiodic portions, it
      is shown that the temporal window of pitch extraction cannot be modeled using a
      single time constant but that the size of the temporal window depends on the
      pitch itself.

PMID- 11303923
TI  - Auditory backward recognition masking in children with a specific language
      impairment and children with a specific reading disability.
AB  - The auditory backward recognition masking (ABRM) and intensity discrimination
      (ID) thresholds of children with a specific language impairment and poor reading
      (SLI-poor readers), children with an SLI and average reading (SLI-average
      readers), children with a specific reading disability and average spoken language
      skills (SRD-average language), and children with normal spoken and written
      language (controls) were estimated with "child-friendly" psychophysical tasks.
      The pattern of ABRM and ID scores suggests that a subset of children with
      concomitant oral language and reading impairments has poor ABRM thresholds, and
      that a subgroup of children with an SLI or SRD has poorer ID thresholds than
      controls. The latter result warns against using rapid auditory processing tasks
      that do not actively control for auditory discrimination ability. Further, some
      unusually poor ABRM scores and ID scores question the validity of extreme scores
      produced by children on psychophysical tasks. Finally, the poor oral language
      scores of many of the children who had impaired reading highlight the need to
      test the oral language skills of SRD samples to ascertain how homogeneous and
      specifically disabled they really are.

PMID- 11303924
TI  - Informational and energetic masking effects in the perception of two simultaneous
      talkers.
AB  - Although most recent multitalker research has emphasized the importance of
      binaural cues, monaural cues can play an equally important role in the perception
      of multiple simultaneous speech signals. In this experiment, the intelligibility
      of a target phrase masked by a single competing masker phrase was measured as a
      function of signal-to-noise ratio (SNR) with same-talker, same-sex, and different
      sex target and masker voices. The results indicate that informational masking,
      rather than energetic masking, dominated performance in this experiment. The
      amount of masking was highly dependent on the similarity of the target and masker
      voices: performance was best when different-sex talkers were used and worst when
      the same talker was used for target and masker. Performance did not, however,
      improve monotonically with increasing SNR. Intelligibility generally plateaued at
      SNRs below 0 dB and, in some cases, intensity differences between the target and
      masking voices produced substantial improvements in performance with decreasing
      SNR. The results indicate that informational and energetic masking play
      substantially different roles in the perception of competing speech messages.

PMID- 11303925
TI  - Elevation localization and head-related transfer function analysis at low
      frequencies.
AB  - Monaural spectral features due to pinna diffraction are the primary cues for
      elevation. Because these features appear above 3 kHz where the wavelength becomes
      comparable to pinna size, it is generally believed that accurate elevation
      estimation requires wideband sources. However, psychoacoustic tests show that
      subjects can estimate elevation for low-frequency sources. In the experiments
      reported, random noise bursts low-pass filtered to 3 kHz were processed with
      individualized head-related transfer functions (HRTFs), and six subjects were
      asked to report the elevation angle around four cones of confusion. The accuracy
      in estimating elevation was degraded when compared to a baseline test with
      wideband stimuli. The reduction in performance was a function of azimuth and was
      highest in the median plane. However, when the source was located away from the
      median plane, subjects were able to estimate elevation, often with surprisingly
      good accuracy. Analysis of the HRTFs reveals the existence of elevation-dependent
      features at low frequencies. The physical origin of the low-frequency features is
      attributed primarily to head diffraction and torso reflections. It is shown that
      simple geometrical approximations and models of the head and torso explain these
      low-frequency features and the corresponding elevations cues.

PMID- 11303926
TI  - Performance of an adaptive beamforming noise reduction scheme for hearing aid
      applications. I. Prediction of the signal-to-noise-ratio improvement.
AB  - Adaptive beamformers have been proposed as noise reduction schemes for
      conventional hearing aids and cochlear implants. A method to predict the amount
      of noise reduction that can be achieved by a two-microphone adaptive beamformer
      is presented. The prediction is based on a model of the acoustic environment in
      which the presence of one acoustic target-signal source and one acoustic noise
      source in a reverberant enclosure is assumed. The acoustic field is sampled using
      two omnidirectional microphones mounted close to the ears of a user. The model
      takes eleven different parameters into account, including reverberation time and
      size of the room, directionality of the acoustic sources, and design parameters
      of the beamformer itself, including length of the adaptive filter and delay in
      the target signal path. An approximation to predict the achievable signal-to
      noise improvement based on the model is presented. Potential applications as well
      as limitations of the proposed prediction method are discussed and a FORTRAN
      subroutine to predict the achievable signal-to-noise improvement is provided.
      Experimental verification of the predictions is provided in a companion paper [J.
      Acoust. Soc. Am. 109, 1134 (2001)].

PMID- 11303927
TI  - Performance of an adaptive beamforming noise reduction scheme for hearing aid
      applications. II. Experimental verification of the predictions.
AB  - A method to predict the amount of noise reduction which can be achieved using a
      two-microphone adaptive beamforming noise reduction system for hearing aids [J.
      Acoust. Soc. Am. 109, 1123 (2001)] is verified experimentally. 34 experiments are
      performed in real environments and 58 in simulated environments and the results
      are compared to the predictions. In all experiments, one noise source and one
      target signal source are present. Starting from a setting in a moderately
      reverberant room (reverberation time 0.42 s, volume 34 m3, distance between
      listener and either sound source 1 m, length of the adaptive filter 25 ms), eight
      different parameters of the acoustical environment and three different design
      parameters of the adaptive beamformer were systematically varied. For those
      experiments, in which the direct-to-reverberant ratios of the noise signal is +3
      dB or less, the difference between the predicted and the measured improvement in
      signal-to-noise ratio (SNR) is -0.21+/-0.59 dB for real environments and -0.25+/
      0.51 dB for simulated environments (average +/- standard deviation). At higher
      direct-to-reverberant ratios, SNR improvement is systematically underestimated by
      up to 5.34 dB. The parameters with the greatest influence on the performance of
      the adaptive beamformer have been found to be the direct-to-reverberant ratio of
      the noise source, the reverberation time of the acoustic environment, and the
      length of the adaptive filter.

PMID- 11303928
TI  - The role of the mora in the timing of spontaneous Japanese speech.
AB  - This study investigates whether the mora is used in controlling timing in
      Japanese speech, or is instead a structural unit in the language not involved in
      timing. Unlike most previous studies of mora-timing in Japanese, this article
      investigates timing in spontaneous speech. Predictability of word duration from
      number of moras is found to be much weaker than in careful speech. Furthermore,
      the number of moras predicts word duration only slightly better than number of
      segments. Syllable structure also has a significant effect on word duration.
      Finally, comparison of the predictability of whole words and arbitrarily
      truncated words shows better predictability for truncated words, which would not
      be possible if the truncated portion were compensating for remaining moras. The
      results support an accumulative model of variance with a final lengthening
      effect, and do not indicate the presence of any compensation related to mora
      timing. It is suggested that the rhythm of Japanese derives from several factors
      about the structure of the language, not from durational compensation.

PMID- 11303929
TI  - Acoustic and linguistic factors in the perception of bandpass-filtered speech.
AB  - Speech can remain intelligible for listeners with normal hearing when processed
      by narrow bandpass filters that transmit only a small fraction of the audible
      spectrum. Two experiments investigated the basis for the high intelligibility of
      narrowband speech. Experiment 1 confirmed reports that everyday English sentences
      can be recognized accurately (82%-98% words correct) when filtered at center
      frequencies of 1500, 2100, and 3000 Hz. However, narrowband low predictability
      (LP) sentences were less accurately recognized than high predictability (HP)
      sentences (20% lower scores), and excised narrowband words were even less
      intelligible than LP sentences (a further 23% drop). While experiment 1 revealed
      similar levels of performance for narrowband and broadband sentences at
      conversational speech levels, experiment 2 showed that speech reception
      thresholds were substantially (>30 dB) poorer for narrowband sentences. One
      explanation for this increased disparity between narrowband and broadband speech
      at threshold (compared to conversational speech levels) is that spectral
      components in the sloping transition bands of the filters provide important cues
      for the recognition of narrowband speech, but these components become inaudible
      as the signal level is reduced. Experiment 2 also showed that performance was
      degraded by the introduction of a speech masker (a single competing talker). The
      elevation in threshold was similar for narrowband and broadband speech (11 dB, on
      average), but because the narrowband sentences required considerably higher sound
      levels to reach their thresholds in quiet compared to broadband sentences, their
      target-to-masker ratios were very different (+23 dB for narrowband sentences and 
      12 dB for broadband sentences). As in experiment 1, performance was better for HP
      than LP sentences. The LP-HP difference was larger for narrowband than broadband
      sentences, suggesting that context provides greater benefits when speech is
      distorted by narrow bandpass filtering.

PMID- 11303930
TI  - Recognition of spectrally asynchronous speech by normal-hearing listeners and
      Nucleus-22 cochlear implant users.
AB  - This experiment examined the effects of spectral resolution and fine spectral
      structure on recognition of spectrally asynchronous sentences by normal-hearing
      and cochlear implant listeners. Sentence recognition was measured in six normal
      hearing subjects listening to either full-spectrum or noise-band processors and
      five Nucleus-22 cochlear implant listeners fitted with 4-channel continuous
      interleaved sampling (CIS) processors. For the full-spectrum processor, the
      speech signals were divided into either 4 or 16 channels. For the noise-band
      processor, after band-pass filtering into 4 or 16 channels, the envelope of each
      channel was extracted and used to modulate noise of the same bandwidth as the
      analysis band, thus eliminating the fine spectral structure available in the full
      spectrum processor. For the 4-channel CIS processor, the amplitude envelopes
      extracted from four bands were transformed to electric currents by a power
      function and the resulting electric currents were used to modulate pulse trains
      delivered to four electrode pairs. For all processors, the output of each channel
      was time-shifted relative to other channels, varying the channel delay across
      channels from 0 to 240 ms (in 40-ms steps). Within each delay condition, all
      channels were desynchronized such that the cross-channel delays between adjacent
      channels were maximized, thereby avoiding local pockets of channel synchrony.
      Results show no significant difference between the 4- and 16-channel full
      spectrum speech processor for normal-hearing listeners. Recognition scores
      dropped significantly only when the maximum delay reached 200 ms for the 4
      channel processor and 240 ms for the 16-channel processor. When fine spectral
      structures were removed in the noise-band processor, sentence recognition dropped
      significantly when the maximum delay was 160 ms for the 16-channel noise-band
      processor and 40 ms for the 4-channel noise-band processor. There was no
      significant difference between implant listeners using the 4-channel CIS
      processor and normal-hearing listeners using the 4-channel noise-band processor.
      The results imply that when fine spectral structures are not available, as in the
      implant listener's case, increased spectral resolution is important for
      overcoming cross-channel asynchrony in speech signals.

PMID- 11303931
TI  - Vowel perception by adults and children with normal language and specific
      language impairment: based on steady states or transitions?
AB  - The current investigation studied whether adults, children with normally
      developing language aged 4-5 years, and children with specific language
      impairment, aged 5-6 years identified vowels on the basis of steady-state or
      transitional formant frequencies. Four types of synthetic tokens, created with a
      female voice, served as stimuli: (1) steady-state centers for the vowels [i] and
      [ae]; (2) voweless tokens with transitions appropriate for [bib] and [baeb]; (3)
      "congruent" tokens that combined the first two types of stimuli into [bib] and
      [baeb]; and (4) "conflicting" tokens that combined the transitions from [bib]
      with the vowel from [baeb] and vice versa. Results showed that children with
      language impairment identified the [i] vowel more poorly than other subjects for
      both the voweless and congruent tokens. Overall, children identified vowels most
      accurately in steady-state centers and congruent stimuli (ranging between 94%
      96%). They identified the vowels on the basis of transitions only from "voweless"
      tokens with 89% and 83.5% accuracy for the normally developing and language
      impaired groups, respectively. Children with normally developing language used
      steady-state cues to identify vowels in 87% of the conflicting stimuli, whereas
      children with language impairment did so for 79% of the stimuli. Adults were
      equally accurate for voweless, steady-state, and congruent tokens (ranging
      between 99% to 100% accuracy) and used both steady-state and transition cues for
      vowel identification. Results suggest that most listeners prefer the steady state
      for vowel identification but are capable of using the onglide/offglide
      transitions for vowel identification. Results were discussed with regard to
      Nittrouer's developmental weighting shift hypothesis and Strange and Jenkin's
      dynamic specification theory.

PMID- 11303932
TI  - The perceptual consequences of within-talker variability in fricative production.
AB  - The effect of talker and token variability on speech perception has engendered a
      great deal of research. However, most of this research has compared listener
      performance in multiple-talker (or variable) situations to performance in single
      talker conditions. It remains unclear to what extent listeners are affected by
      the degree of variability within a talker, rather than simply the existence of
      variability (being in a multitalker environment). The present study has two
      goals: First, the degree of variability among speakers in their /s/ and /S/
      productions was measured. Even among a relatively small pool of talkers, there
      was a range of speech variability: some talkers had /s/ and /S/ categories that
      were quite distinct from one another in terms of frication centroid and skewness,
      while other speakers had categories that actually overlapped one another. The
      second goal was to examine whether this degree of variability within a talker
      influenced perception. Listeners were presented with natural /s/ and /S/ tokens
      for identification, under ideal listening conditions, and slower response times
      were found for speakers whose productions were more variable than for speakers
      with more internal consistency in their speech. This suggests that the degree of
      variability, not just the existence of it, may be the more critical factor in
      perception.

PMID- 11303933
TI  - Relations between intelligibility of narrow-band speech and auditory functions,
      both in the 1-kHz frequency region.
AB  - Relations between perception of suprathreshold speech and auditory functions were
      examined in 24 hearing-impaired listeners and 12 normal-hearing listeners. The
      speech intelligibility index (SII) was used to account for audibility. The
      auditory functions included detection efficiency, temporal and spectral
      resolution, temporal and spectral integration, and discrimination of intensity,
      frequency, rhythm, and spectro-temporal shape. All auditory functions were
      measured at 1 kHz. Speech intelligibility was assessed with the speech-reception
      threshold (SRT) in quiet and in noise, and with the speech-reception bandwidth
      threshold (SRBT), previously developed for investigating speech perception in a
      limited frequency region around 1 kHz. The results showed that the elevated SRT
      in quiet could be explained on the basis of audibility. Audibility could only
      partly account for the elevated SRT values in noise and the deviant SRBT values,
      suggesting that suprathreshold deficits affected intelligibility in these
      conditions. SII predictions for the SRBT improved significantly by including the
      individually measured upward spread of masking in the SII model. Reduced spectral
      resolution, reduced temporal resolution, and reduced frequency discrimination
      appeared to be related to speech perception deficits. Loss of peripheral
      compression appeared to have the smallest effect on the intelligibility of
      suprathreshold speech.

PMID- 11303934
TI  - A numerical method to predict the effects of frequency-dependent attenuation and
      dispersion on speed of sound estimates in cancellous bone.
AB  - Many studies have demonstrated that time-domain speed-of-sound (SOS) measurements
      in calcaneus are predictive of osteoporotic fracture risk. However, there is a
      lack of standardization for this measurement. Consequently, different
      investigators using different measurement systems and analysis algorithms obtain
      disparate quantitative values for calcaneal SOS, impairing and often precluding
      meaningful comparison and/or pooling of measurements. A numerical method has been
      developed to model the effects of frequency-dependent attenuation and dispersion
      on transit-time-based SOS estimates. The numerical technique is based on a
      previously developed linear system analytic model for Gaussian pulses propagating
      through linearly attenuating, weakly dispersive media. The numerical approach is
      somewhat more general in that it can be used to predict the effects of arbitrary
      pulse shapes and dispersion relationships. The numerical technique, however,
      utilizes several additional assumptions (compared with the analytic model) which
      would be required for the practical task of correcting existing clinical
      databases. These include a single dispersion relationship for all calcaneus
      samples, a simple linear model relating phase velocity to broadband ultrasonic
      attenuation, and a constant calcaneal thickness. Measurements on a polycarbonate
      plate and 30 human calcaneus samples were in good quantitative agreement with
      numerical predictions. In addition, the numerical approach predicts that in
      cancellous bone, frequency-dependent attenuation tends to be a greater
      contributor to variations in transit-time-based SOS estimates than dispersion.
      This approach may be used to adjust previously acquired individual measurements
      so that SOS data recorded with different devices using different algorithms may
      be compared in a meaningful fashion.

PMID- 11303935
TI  - Acoustic nonlinearity parameter tomography for biological tissues via parametric
      array from a circular piston source--theoretical analysis and computer
      simulations.
AB  - The acoustic nonlinearity parameter B/A describes the nonlinear features of a
      medium and may become a novel parameter for ultrasonic tissue characterization.
      This paper presents a theoretical analysis for acoustic nonlinear parameter
      tomography via a parametric array. As two primary waves of different frequencies
      are radiated simultaneously from a circular piston source, a secondary wave at
      the difference frequency is generated due to the nonlinear interaction of the
      primary waves. The axial and radial distributions of sound pressure amplitude for
      the generated difference frequency wave in the near field are calculated by a
      superposition of Gaussian beams. The calculated results indicated that the
      difference frequency component of the parametric array grows linearly with
      distance from the piston source. It therefore provides a better source to do the
      acoustic nonlinearity parameter tomography because the fundamental and second
      harmonic signals both have a near field that goes through many oscillations due
      to diffraction. By using a finite-amplitude insert substitution method and a
      filtered convolution algorithm, a computer simulation for B/A tomography from the
      calculated sound pressure of the difference frequency wave is studied. For
      biological tissues, the sound attenuation is considered and compensated in the
      image reconstruction. Nonlinear parameter computed tomography (CT) images for
      several biological sample models are obtained with quite good quality in this
      study.

PMID- 11303936
TI  - Dynamic photoelastic study of the transient stress field in solids during shock
      wave lithotripsy.
AB  - Photoelastic and shadowgraph imaging techniques were used to visualize the
      propagation and evolution of stress waves, and the resultant transient stress
      fields in solids during shock wave lithotripsy. In parallel, theoretical analysis
      of the wavefront evolution inside the solids was performed using a ray-tracing
      method. Excellent agreement between the theoretical prediction and experimental
      results was observed. Both the sample size and geometry were found to have a
      significant influence on the wave evolution and associated stress field produced
      inside the solid. In particular, characteristic patterns of spalling damage
      (i.e., transverse and longitudinal crack formation) were observed using plaster
      of-Paris cylindrical phantoms of rectangular and circular cross sections. It was
      found that the leading tensile pulse of the reflected longitudinal wave is
      responsible for the initiation of microcracks in regions inside the phantom where
      high tensile stresses are produced. In addition, the transmitted shear wave was
      found to play a critical role in facilitating the extension and propagation of
      the microcrack.

PMID- 11303937
TI  - Characteristics of whistles from the acoustic repertoire of resident killer
      whales (Orcinus orca) off Vancouver Island, British Columbia.
AB  - The acoustic repertoire of killer whales (Orcinus orca) consists of pulsed calls
      and tonal sounds, called whistles. Although previous studies gave information on
      whistle parameters, no study has presented a detailed quantitative
      characterization of whistles from wild killer whales. Thus an interpretation of
      possible functions of whistles in killer whale underwater communication has been
      impossible so far. In this study acoustic parameters of whistles from groups of
      individually known killer whales were measured. Observations in the field
      indicate that whistles are close-range signals. The majority of whistles (90%)
      were tones with several harmonics with the main energy concentrated in the
      fundamental. The remainder were tones with enhanced second or higher harmonics
      and tones without harmonics. Whistles had an average bandwidth of 4.5 kHz, an
      average dominant frequency of 8.3 kHz, and an average duration of 1.8 s. The
      number of frequency modulations per whistle ranged between 0 and 71. The study
      indicates that whistles in wild killer whales serve a different function than
      whistles of other delphinids. Their structure makes whistles of killer whales
      suitable to function as close-range motivational sounds.

PMID- 11303938
TI  - Neural representation of sound amplitude by functionally different auditory
      receptors in crickets.
AB  - The physiological characteristics of auditory receptor fibers (ARFs) of crickets,
      a model system for studying auditory behaviors and their neural mechanisms, are
      investigated. Unlike auditory receptor neurons of many animals, cricket ARFs fall
      into three distinct populations based on characteristic frequency (CF) [Imaizumi
      and Pollack, J. Neurosci. 19, 1508-1516 (1999)]. Two of these have CFs similar to
      the frequency component of communication signals or of ultrasound produced by
      predators, and a third population has intermediate CF. Here, sound-amplitude
      coding by ARFs is examined to gain insights to how behaviorally relevant sounds
      are encoded by populations of receptor neurons. ARFs involved in acoustic
      communication comprise two distinct anatomical types, which also differ in
      physiological parameters (threshold, response slope, dynamic range, minimum
      latency, and sharpness of tuning). Thus, based on CF and anatomy, ARFs comprise
      four populations. Physiological parameters are diverse, but within each
      population they are systematically related to threshold. The details of these
      relationships differ among the four populations. These findings open the
      possibility that different ARF populations differ in functional organization.

PMID- 11303939
TI  - Wave localization on a submerged cylindrical shell with rib aperiodicity.
AB  - The results of a numerical study of vibration localization due to stiffener
      variability in a framed shell are reported. An axisymmetric finite element (FE)
      infinite element model is used to obtain predictions in good general agreement
      with previously reported experimental results. Over the frequency band of this
      study, up to three times the ring frequency, two structural resonances dominate
      the vibratory response of the shell for high circumferential orders (n > 10).
      Localization is shown to be linked to the sensitivity of the local resonance
      frequencies of the system to specific geometrical parameters. Specifically, rib
      thickness variations strongly affect the first pass band, while rib spacing
      variations strongly affect the second pass band.

PMID- 11303940
TI  - Acoustic scattering by a circular cylinder parallel with another of small radius.
AB  - The scattering of a plane acoustic wave by an infinite penetrable or impenetrable
      circular cylinder, parallel with another one, also penetrable or impenetrable, of
      acoustically small radius, is considered. The method of separation of variables,
      in conjunction with translational addition theorems for cylindrical wave
      functions, is used. Analytical expressions are obtained for the scattered
      pressure field and the various scattering cross sections, for normal incidence.
      Numerical results are given for penetrable and impenetrable cylinders.

PMID- 11303941
TI  - Low-frequency scattering of acoustic waves by a bounded rough surface in a half
      plane.
AB  - The problem of the scattering of harmonic plane waves by a rough half-plane is
      studied here. The surface roughness is finite. The slope of the irregularity is
      taken as arbitrary. Two boundary conditions are considered, those of Dirichlet
      and Neumann. An asymptotic solution is obtained, when the wavelength lambda of
      the incident wave is much larger than the characteristic length of the roughness
      iota, by means of the method of matched asymptotic expansions in terms of the
      small parameter epsilon= 2piiota/lambda. For the Dirichlet problem, the solution
      of the near and far fields is obtained up to O(epsilon2). The far field solution
      is given in terms of a coefficient that have a simple explicit expression, which
      also appears in the corresponding solution to the Neumann problem, already
      solved. Also the scattering cross section is given by simple formulas to
      O(epsilon3). It is noted that, for the Dirichlet problem, the leading term is of
      order epsilon3 which, by contrast, is different from that of the circular
      cylinder in full space, that is, of order epsilon(-1) (log epsilon)(-2). Some
      examples display the simplicity of the general results based on conformal
      mapping, which involve arcs of circle, polygonal lines, surface cracks and the
      like.

PMID- 11303942
TI  - Guided waves in a transversely isotropic cylinder immersed in a fluid.
AB  - Propagation of flexural guided waves in a fluid-loaded transversely isotropic
      cylinder is studied. Numerical results are presented for a cobalt cylinder
      immersed in water. The phase velocities are not significantly affected except for
      several modes in which the energy leakage occurs into the fluid over certain
      frequency ranges. Attenuation spectra for the leaking modes are plotted.

PMID- 11303943
TI  - Gas bubble pulsation in a semiconfined space subjected to ultrasound.
AB  - In the case of ultrasound application in biological tissues, gas bubbles might
      form and collapse within cells, in the intercellular spaces and on tissue
      surfaces. In this work the effect of confined space on the behavior of the gas
      bubble in the presence of ultrasonic field is studied. A numerical model for
      bubble pulsation in a planar liquid layer, bounded by two rigid walls, is
      developed. Surface tension at the interface between the host liquid and the gas
      in the bubble is considered as well. A mathematical statement and solution
      technique based on the boundary integral method are presented. In some cases, the
      bubble divides into two symmetrical parts and high-velocity jets are generated,
      aimed at the walls. The final velocity of the jets strongly depends on the
      surface tension of the host liquid. Two new parameters that predict the
      occurrence of jet formation are developed.

PMID- 11303944
TI  - A computational analysis of sonic booms penetrating a realistic ocean surface.
AB  - The last decade has seen a revival of sonic boom research, a direct result of the
      projected market for a new breed of supersonic passenger aircraft, its design,
      and its operation. One area of the research involves sonic boom penetration into
      the ocean, one concern being the possible disturbance of marine mammals from the
      noise generated by proposed high-speed civil transport (HSCT) flyovers. Although
      theory is available to predict underwater sound levels due to a sonic boom
      hitting a homogeneous ocean with a flat surface, theory for a realistic ocean,
      one with a wavy surface and bubbles near the surface, is missing and will be
      presented in this paper. First, reviews are given of a computational method to
      calculate the underwater pressure field and the effects of a simple wavy ocean
      surface on the impinging sonic boom. Second, effects are described for the
      implementation of three additional conditions: a sonic boom/ocean "wavelength"
      comparison, complex ocean surfaces, and bubbles near the ocean surface. Overall,
      results from the model suggest that the realistic ocean features affect the
      penetrating proposed HSCT sonic booms by modifying the underwater sound-pressure
      levels only about 1 decibel or less.

PMID- 11303945
TI  - A unified model for reverberation and submerged object scattering in a stratified
      ocean waveguide.
AB  - A unified model for reverberation and submerged target scattering in a stratified
      medium is developed from wave theory. The advantage of the unified approach is
      that it enables quantitative predictions to be made of the target-echo-to
      reverberation ratio in an ocean waveguide. Analytic expressions are derived for
      both deterministic and stochastic scattering from the seafloor and subseafloor.
      Asymptotic techniques are used to derive expressions for the scattering of
      broadband waveforms from distant objects or surfaces. Expressions are then
      obtained for the scattered field after beamforming with a horizontal line array.
      The model is applied to problems of active detection in shallow water. Sample
      calculations for narrow-band signals indicate that the detection of submerged
      target echoes above diffuse seafloor reverberation is highly dependent upon water
      column and sediment stratification as well as array aperture, source, receiver,
      and target locations, in addition to the scattering properties of the target and
      seafloor. The model is also applied to determine the conditions necessary for
      echo returns from discrete geomorphologic features of the seafloor and
      subseafloor to stand prominently above diffuse seafloor reverberation. This has
      great relevance to the geologic clutter problem encountered by active sonar
      systems operating in shallow water, as well as to the remote sensing of
      underwater geomorphology.

PMID- 11303946
TI  - High-amplitude thermoacoustic effects in a single pore.
AB  - Nonlinear effects on thermoacoustic gain in a single pore are investigated
      experimentally. By creating a sharp temperature gradient in a uniform cross
      section pore, the effect of high displacement amplitudes relative to the stack
      length is isolated from other high amplitude effects and also from effects due to
      geometrical discontinuities. The experiment probes displacement amplitudes which
      lie beyond the range of validity of the linear theory. The complex
      compressibility of nitrogen gas in the pore is measured for displacement
      amplitudes ranging from 2.5% to 60% of the stack length. No changes in the
      thermoacoustic response are observed over this range. Extending the upper limit
      to 175%, the power flow, as a function of the squared ratio of the displacement
      amplitude and the stack length, behaves linearly over the entire range.

PMID- 11303947
TI  - Equivalent circuits and directivity patterns of air-coupled ultrasonic
      transducers.
AB  - Air-coupled transducers for producing ultrasonic radiation in gases are studied.
      The transducer consists of a circular thin plate in flexural vibration and a
      sandwich longitudinal electromechanical vibrator that is attached to the center
      of the plate. The lowest-order axially symmetric flexural vibrational mode of a
      circular thin plate is analyzed. The equivalent circuits of the circular plate in
      flexural vibration and the compound transducer are presented and the frequency
      equation is derived. The radiated ultrasonic field of the circular thin plate in
      flexural vibration is calculated and the directivity pattern is obtained
      theoretically. Some transducers of this type are designed according to the
      frequency equation, and their resonance frequencies are measured. The measured
      resonance frequencies are in good agreement with the theoretical results, and the
      calculated radiation ultrasonic field is also in good agreement with the measured
      results of a previous work.

PMID- 11303948
TI  - Robustness to head misalignment of virtual sound imaging systems.
AB  - When binaural sound signals are presented with two loudspeakers, the listener's
      ears are required to be in the relatively small region which is under control of
      the system. Misalignment of the head results in inaccurate synthesis of the
      binaural signals. Consequently, directional information associated with the
      acoustic signals is inaccurately reproduced. When the two loudspeakers are placed
      close together, the spatial rate of change of the generated sound field is much
      smaller than that generated by two loudspeakers spaced apart. Therefore, the
      performance of such a system is expected to be more robust to misalignment of the
      listener's head. Robustness of performance is investigated here with respect to
      head displacement in three translational and three rotational directions. A
      comparison is given between systems consisting of two loudspeakers either placed
      close together or spaced apart. The extent of effective control with head
      displacement and the resulting deterioration in directional information is
      investigated in the temporal and spectral domain by analyzing synthesized
      binaural signals. Subjective localization experiments are performed for cases in
      which notable differences in performance are expected from the previous analysis.
      It is shown that the system comprising two loudspeakers that are close together
      is very robust to misalignment of the listener's head.

PMID- 11303949
TI  - Implication of conservative and gyroscopic forces on vibration and stability of
      an elastically tailored rotating shaft modeled as a composite thin-walled beam.
AB  - Problems related with the implications of conservative and gyroscopic forces on
      vibration and the stability of a circular cylindrical shaft modeled as a thin
      walled composite beam and spinning with constant angular speed about its
      longitudinal axis are addressed. Taking into account the directionality property
      of fiber reinforced composite materials, it is shown that for a shaft featuring
      flapwise-chordwise-bending coupling, a dramatic enhancement of both the
      vibrational and stability behavior can be reached. In addition, the effects
      played in the same context by transverse shear, rotatory inertias as well as by
      the various boundary conditions are discussed and pertinent conclusions are
      outlined.

PMID- 11303950
TI  - A new method for true and spurious eigensolutions of arbitrary cavities using the
      combined Helmholtz exterior integral equation formulation method.
AB  - Integral equation methods have been widely used to solve interior eigenproblems
      and exterior acoustic problems (radiation and scattering). It was recently found
      that the real-part boundary element method (BEM) for the interior problem results
      in spurious eigensolutions if the singular (UT) or the hypersingular (LM)
      equation is used alone. The real-part BEM results in spurious solutions for
      interior problems in a similar way that the singular integral equation (UT
      method) results in fictitious solutions for the exterior problem. To solve this
      problem, a Combined Helmholtz Exterior integral Equation Formulation method
      (CHEEF) is proposed. Based on the CHEEF method, the spurious solutions can be
      filtered out if additional constraints from the exterior points are chosen
      carefully. Finally, two examples for the eigensolutions of circular and
      rectangular cavities are considered. The optimum numbers and proper positions for
      selecting the points in the exterior domain are analytically studied. Also,
      numerical experiments were designed to verify the analytical results. It is worth
      pointing out that the nodal line of radiation mode of a circle can be rotated due
      to symmetry, while the nodal line of the rectangular is on a fixed position.

PMID- 11303951
TI  - Modeling vibrational energy transmission at bolted junctions between a plate and
      a stiffening rib.
AB  - An analytical model is presented for structure-borne sound transmission at a
      bolted junction in a rib-stiffened plate structure. The model is based on the
      wave approach for junctions of semi-infinite plates and calculates coupling loss
      factors required by statistical energy analysis. The stiffening rib is modeled as
      a plate strip and the junction is represented by an elastic interlayer with a
      spatially dependent stiffness. Experimental verification is carried out on a
      series of Plexiglas plate structures with varying rib depth and bolt spacing. A
      well-defined connection length at the junction was created by inserting thin
      spacers between the plate and the rib at each bolt. Comparison between numerical
      and experimental data for this case showed good agreement. Measured results for
      the bolted junction without spacers suggested that structure-borne sound
      transmission could be modeled as a series of connections characterized by a
      finite connection length. This concept is explored further by determining an
      equivalent connection length which gives the best agreement between numerical and
      experimental data.

PMID- 11303952
TI  - Photodynamic therapy of skin cancers: sensitizers, clinical studies and future
      directives.
AB  - Photodynamic therapy (PDT) is a new modality of skin cancer treatment. It
      involves the administration of photosensitizing drugs which, when localized in
      tumor tissue can produce its destruction by absorbing an adequate dose of light
      of an appropriate wavelength. A large number of photosensitizing agents have been
      tested in PDT experiments. Topical application of 5-aminolevulinic acid (5-ALA)
      followed by light irradiation is the most commonly used method. 5-ALA is a
      prodrug converted in situ via the heme cycle into protoporphyrin IX, an effective
      photosensitizer agent. Treatment of nonmelanoma skin cancers by PDT has met with
      varying degrees of success. In the case of 5-ALA, this therapy's main limitation
      is the poor penetration of 5-ALA into skin, due to hydrophilic and charge
      characteristics. However, the efficacy of 5-ALA-PDT may be improved by (a)
      development of adequate drug delivery systems; (b) use of enhancers of PpIX
      production and accumulation in target tissue, and (c) modifications of the 5-ALA
      molecule. Optimal timing, light sources, doses, and number of applications are
      also important factors for topical 5-ALA therapy and must be well defined. The
      aim of this review is to highlight recent progress in 5-ALA-PDT of skin cancer,
      and to present ways holding promise for its improvement.

PMID- 11303953
TI  - Influence of passive permeability on apparent P-glycoprotein kinetics.
AB  - PURPOSE: The objectives of this work were to evaluate the importance of moderate
      passive permeability on apparent P-glycoprotein (P-gp) kinetics, and demonstrate
      that inspection of basolateral to apical and apical to basolateral (BL-AP/AP-BL)
      permeability ratios may result in a compound being overlooked as a P-gp substrate
      and inhibitor of another drug's transport via P-gp inhibition. METHODS: The
      permeability ratios of nicardipine, vinblastine, cimetidine, and ranitidine were
      determined across Caco-2 monolayers that express P-gp, in the presence and
      absence of the specific P-gp inhibitor, GF120918. In addition, the permeability
      ratio of vinblastine was studied after pretreatment of Caco-2 monolayers with
      nicardipine, ranitidine, or cimetidine. Similar studies were repeated with hMDRI
      MDCK monolayers. RESULTS: The permeability ratios for cimetidine and vinblastine
      were >2. The permeability ratios for nicardipine and ranitidine were close to
      unity, and were not affected by the addition of GF120918. Based solely on ratios,
      only compounds with moderate transcellular permeability (vinblastine and
      cimetidine) would be identified as P-gp substrates. Although the permeability
      ratios appeared to be unity for nicardipine and ranitidine, both compounds
      affected the permeability of vinblastine, and were identified as substrates and
      inhibitors of P-gp. Studies performed in hMDR1-MDCK cells confirmed these
      experimental results. Data were explained in the context of a kinetic model,
      where passive permeability and P-gp efflux contribute to overall drug transport.
      CONCLUSIONS: Moderate passive permeability was necessary for P-gp to reduce the
      AP-BL drug permeability. Inspection of the permeability ratio after directional
      transport studies did not effectively identify P-gp substrates that affected the
      P-gp kinetics of vinblastine. Because of the role of passive permeability, drug
      interaction studies with known P-gp substrates, rather than directional
      permeability studies, are needed to elucidate a more complete understanding of P
      gp kinetics.

PMID- 11303954
TI  - Development of novel lipophilic derivatives of DADLE (leucine enkephalin
      analogue): intestinal permeability characateristics of DADLE derivatives in rats.
AB  - PURPOSE: The objective of this study is to examine the intestinal permeability of
      novel lipophilic derivatives of DADLE (Tyr-D-Ala-Gly-Phe-D-Leu), an enkephalin
      analogue, using isolated rat intestinal membranes. METHODS: The novel lipophilic
      derivatives of DADLE were synthesized by chemical modification with various fatty
      acids at the C terminus. The pharmacological activities of these DADLE
      derivatives were assessed by a hot plate test. The intestinal permeability of
      these derivatives was estimated by the in vitro Ussing chamber method. RESULTS:
      We obtained four different DADLE derivatives including acetyl-DADLE (DADLE-C2),
      butyryl-DADLE (DADLE-C4), caproyl-DADLE (DADLE-C6), and caprylyl-DADLE (DADLE
      C8). All the derivatives of DADLE had at least 75% of the activity of native
      DADLE, suggesting that chemical modification of DADLE at the C terminus did not
      markedly affect its pharmacological activity. These DADLE derivatives were more
      stable than native DADLE in jejunal and colonic homogenates. A "bell-shaped"
      profile was observed between the apparent permeability coefficients (Papp) of
      DADLE derivatives and lipophilicity. In particular, DADLE-C4 had the greatest
      permeability characteristics across the intestinal membrane of the acyl
      derivatives studied in this experiment. The permeability of DADLE-C4 across the
      jejunal membrane was further improved in the presence of puromycin, amastatin,
      and sodium glycocholate (NaGC), all at a concentration of 0.5 mM. CONCLUSIONS: We
      suggest that the combination of chemical modification with butyric acid and the
      application of a protease inhibitor are effective for improving the absorption of
      DADLE across the intestinal membrane.

PMID- 11303956
TI  - Drug distribution in human skin using two different in vitro test systems:
      comparison with in vivo data.
AB  - PURPOSE: Two in vitro test systems used to study drug penetration into human skin
      -the Franz diffusion cell (FD-C) and the Saarbruecken penetration model (SB-M)-
      were evaluated, and the results were compared with data gained under analogous in
      vivo conditions. METHODS: Excised human skin was used in all in vitro
      experiments. Flufenamic acid dissolved in wool alcohols ointment, was chosen as a
      model drug, and the preparation was applied using 'infinite dose' conditions. To
      acquire quantitative information about the drug penetration, the skin was
      segmented into surface parallel sections at the end of each experiment, first by
      tape stripping the stratum corneum (SC), and second by cutting the deeper skin
      layers with a cryomicrotome. The flufenamic acid was extracted from each sample
      and assayed by high performance liquid chromatography (HPLC). For in vivo
      experiments, only the tape stripping technique was used. RESULTS: a) Drug
      penetration into the SC: In both in vitro test systems the total drug amounts
      detected in the SC were found to increase over the different incubation times.
      Similar conditions were obtained in vivo, but on a lower level. Using Michaelis
      Menten kinetics, the m(max) value was calculated for the skin of two donors. The
      relations of the m(max) values for the FD-C and the SB-M closely correspond (1.26
      [donor 1] and 1.29 [donor 2]). A direct linear correlation of the drug amount in
      the SC and the time data were found for in vivo with both in vitro test systems.
      b) Drug penetration into the deeper skin layers: The detected drug amounts in the
      deeper skin layers continuously increased with the incubation time in the SB-M,
      while in the FD-C, only very small drug amounts were observed after incubation
      times of 30 and 60 minutes. It was also noticed, that the drug amounts rose
      steeply at time points 3 and 6 hours. Additional studies showed a remarkable
      penetration of water into the skin from the basolateral acceptor compartment in
      the FD-C. This could explain the different drug transport into the deeper skin
      layers between the two in vitro test systems. CONCLUSIONS: Both in vitro models
      showed comparable results for the drug penetration into the SC and a robust
      correlation with in vitro data. Different results were obtained for the deeper
      skin layers. Whether a correlation between in vitro and in vivo data is also
      possible here has to be investigated by further experiments.

PMID- 11303955
TI  - Design and in vivo evaluation of an oral delivery system for insulin.
AB  - PURPOSE: To develop an oral controlled release system for insulin. METHODS: The
      polymer-inhibitor conjugates carboxymethylcellulose (CMC)-Bowman-Birk inhibitor
      and CMC-elastatinal were homogenized with polycarbophil-cysteine conjugate,
      insulin, and mannitol, compressed to 2 mg microtablets and enteric coated with a
      polymethacrylate. The protective effect of this delivery system for insulin
      towards enzymatic degradation, as well as the release profile, was evaluated in
      vitro. In addition, the effect of the dosage form on glucose levels of diabetic
      mice was determined. RESULTS: Tablets containing the CMC-inhibitor conjugates
      showed a strong protective effect for insulin. Whereas 91.6 +/- 7.4% (mean +/-
      SD, n = 3) of insulin in the dosage form without the inhibitor conjugates has
      been degraded within 3 h of incubation in an artificial intestinal fluid
      containing physiological concentrations of trypsin, chymotrypsin, and elastase,
      49.7 +/- 5.5% (mean +/- SD, n = 3) of insulin remained stable in the delivery
      system containing the polymer-inhibitor conjugates. Additionally, polycarbophil
      cysteine (PCP-Cys) provides high cohesiveness of the dosage form, due to the
      formation of interas well as intramolecular disulfide bonds within the polymer
      matrix. According to this, a controlled release of insulin could be achieved over
      a time period of 10 h. Furthermore, in vivo studies in diabetic mice showed a
      decrease in basal glucose levels of 20% to 40% during a time period of 80 h.
      CONCLUSIONS: Mucoadhesive polymer-inhibitor conjugates might represent a
      promising excipient in delivery systems for oral (poly)peptide delivery.

PMID- 11303957
TI  - Inhibition of angiotensin II-induced inositol phosphate production by triacid
      nonpeptide antagonists in CHO cells expressing human AT1 receptors.
AB  - PURPOSE: The aim of the present work is to describe the inhibitory properties of
      LY301875 and LY303336, two polysubstituted 4-aminoimidazole AT1 receptor
      antagonists, on CHO cells expressing human recombinant AT1 receptors. METHODS:
      The binding of [3H]-angiotensin II to intact cells as well as to angiotensin II
      induced inositol phosphate accumulation is measured. RESULTS: Both antagonists
      inhibit specific [3H]-angiotensin II binding to AT1 receptors in these cells,
      with IC50 values of 5.9 and 5.2 nM, respectively. Preincubation of the cells with
      LY301875 results in a decline of up to 80% of the maximal angiotensin II
      stimulated inositol phosphate (IP) production. A near complete decline of the
      maximal response is observed for LY303336. This insurmountable inhibition is
      attenuated for both antagonists when losartan is included during the
      preincubation of the cells. CONCLUSIONS: Functional recovery experiments, in
      which antagonist-preincubated cells are washed and exposed to fresh media,
      suggest that the insurmountable inhibition by LY301875 and LY303336 is related to
      their relatively slow dissociation from the AT1 receptors. As already described
      for losartan and the derived insurmountable AT1 antagonists candesartan. EXP3174,
      and irbesartan, coincubation experiments reveal that LY301875 and LY303336
      interact with the AT1 receptor in a manner that is competitive with angiotensin
      II.

PMID- 11303958
TI  - Dexamethasone megadoses stabilize rat liver lysosomal membranes by non-genomic
      and genomic effects.
AB  - PURPOSE: Membrane-stabilizing effects may be part of glucocorticoid action during
      high-dose glucocorticoid therapy. The present study investigates the mode of
      action of dexamethasone megadoses on rat liver lysosomal membranes. METHODS:
      Following intravenous administration of dexamethasone in rats, the release of
      beta-glucuronidase from liver lysosomes was assessed ex vivo as a marker for
      lysosomal membrane integrity. RESULTS: Dexamethasone megadoses significantly
      inhibited beta-glucuronidase release 10 min post-administration by 38% (3 mg/kg
      dexamethasone) and 33% (10 mg/kg dexamethasone) at corresponding dexamethasone
      liver concentrations of 3.9 x 10(-5) mol/kg and 15.1 x 10(-5) mol/kg,
      respectively. Comparable inhibition of beta-glucuronidase release (34% for 3
      mg/kg and 38% for 10 mg/kg) was observed 24 h after administration of
      dexamethasone, although dexamethasone liver concentrations had already declined
      to 0.09 x 10(-5) mol/kg and 0.19 x 10(-5) mol/kg, respectively. A 2-h oral
      pretreatment of rats with the glucocorticoid receptor antagonist RU 486 (10
      mg/kg) did not alter immediate (10 min) stabilization by dexamethasone (3 mg/kg).
      but almost completely prevented lysosomal membrane protection 24 h after
      dexamethasone injection. CONCLUSIONS: Dexamethasone megadoses may preserve
      lysosomal membrane integrity by a dual action involving both rapid nongenomic
      effects occurring instantaneously after administration and long-term receptor
      dependent genomic events.

PMID- 11303959
TI  - Safety, toxicokinetics and tissue distribution of long-term intravenous liposomal
      amphotericin B (AmBisome): a 91-day study in rats.
AB  - PURPOSE: Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and
      produces higher plasma concentrations than other formulations. Because liposomes
      may increase and prolong tissue exposures, the potential for drug accumulation or
      delayed toxicity after chronic AmBisome was investigated. METHODS: Rats (174/sex)
      received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes
      for 91 days with a 30-day recovery. Safety (including clinical and microscopic
      pathology) and toxicokinetics in plasma and tissues were evaluated. RESULTS:
      Chemical and histopathologic changes demonstrated that the kidneys and liver were
      the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate
      (urean nitrogen [BUN] < or = 51 mg/dl; creatinine unchanged). Liposome-related
      changes (vacuolated macrophages and hypercholesterolemia) were also observed.
      Although plasma and tissue accumulation was nonlinear and progressive (clearance
      and volume decreased, half-life increased with dose and time), most toxic changes
      occurred early, stabilized by the end of dosing, and reversed during recovery.
      There were no delayed toxicities. Concentrations in liver and spleen greatly
      exceeded those in plasma: kidney and lung concentrations were similar to those in
      plasma. Elimination half-lives were 1-4 weeks in all tissues. CONCLUSIONS:
      Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal
      toxicities after 91 days, with no new or delayed effects after prolonged
      treatment at high doses that resulted in plasma levels >200 microg/ml and tissue
      levels >3000 microg/g.

PMID- 11303960
TI  - Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer
      (NX1838) following injection into the vitreous humor of rhesus monkeys.
AB  - PURPOSE: The objective of this study was to determine the pharmacokinetics and
      safety for NX1838 following injection into the vitreous humor of rhesus monkeys.
      METHODS: Plasma and vitreous humor pharmacokinetics were determined following a
      single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the
      pharmacokinetics and toxicological properties of NX1838 were determined following
      six biweekly bilateral injections of 0.25 or 0.50 mg/eye or following four
      biweekly bilateral injections of 0.10 mg per eye followed by two biweekly
      bilateral injections of 1.0 mg per eye. RESULTS: Plasma and vitreous humor NX1838
      concentrations were linearly related to the dose administered. NX1838 was cleared
      intact from the vitreous humor into the plasma with a half-life of approximately
      94 h, which was in agreement with the plasma terminal half-life. Vascular
      endothelial growth factor (VEGF)-binding assays demonstrated that the NX1838
      remaining in the vitreous humor after 28 days was fully active. No toxicological
      effects or antibody responses were evident. CONCLUSIONS: The no observable effect
      level was greater than six biweekly bilateral 0.50 mg/eye doses or two biweekly
      bilateral 1.0 mg/eye doses. These pharmacokinetic and safety data support monthly
      1 or 2 mg/eye dose regimens in human clinical trials.

PMID- 11303961
TI  - Hepatic disposition of fexofenadine: influence of the transport inhibitors
      erythromycin and dibromosulphothalein.
AB  - PURPOSE: To examine the disposition of fexofenadine in the isolated perfused rat
      liver and the influence of erythromycin and dibromosulphthalein (DBSP) on the
      hepatic uptake and biliary excretion of fexofenadine. METHODS: Livers from four
      groups of rats were perfused in a recirculatory manner with fexofenadine HCl
      added as a bolus (125, 250, 500, or 1000 microg) to perfusate. Livers from
      another three groups of rats were perfused with 250 microg of fexofenadine HCl.
      With one group as control, erythromycin (4.0 microg/ml) or DBSP (136 microg/ml)
      was added to the perfusate of the other groups. In all experiments, perfusate and
      bile were collected for 60 min; in addition, livers from the second experiment
      were retained for assay. Fexofenadine was determined in perfusate, bile, and
      homogenized liver by HPLC. RESULTS: The area under the curve (AUC) of
      fexofenadine was linearly related to concentration. It was unchanged from control
      (12,800 +/- 200 ng x h/ml) by erythromycin (14,400 +/- 2000 ng x h/ml), but was
      increased 95% by DBSP (25,000 +/- 2600 ng x h/ml, P <0.001). The ratios of the
      concentrations of fexofenadine in liver/perfusate were decreased significantly by
      DBSP; those for bile/liver were increased by erythromycin. CONCLUSIONS:
      Erythromycin reduced the canalicular transport of fexofenadine into bile, whereas
      DBSP reduced uptake across the sinusoidal membrane.

PMID- 11303962
TI  - A human physiologically-based model for glycyrrhzic acid, a compound subject to
      presystemic metabolism and enterohepatic cycling.
AB  - PURPOSE: To analyze the role of the kinetics of glycyrrhizic acid (GD) in its
      toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been
      developed for humans. METHODS: The kinetics of GD, which is absorbed as
      glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a
      rat model. After rat to human extrapolation, the model was validated on plasma
      concentration data after ingestion of GA and GD solutions or licorice
      confectionery, and an additional data derived from the literature. Observed
      interindividual variability in kinetics was quantified by deriving an optimal set
      of parameters for each individual. RESULTS: The a-priori defined model
      successfully forecasted GA kinetics in humans, which is characterized by a second
      absorption peak in the terminal elimination phase. This peak is subscribed to
      enterohepatic cycling of GA metabolites. The optimized model explained most of
      the interindividual variance, observed in the clinical study, and adequately
      described data from the literature. CONCLUSIONS: Preclinical information on GD
      kinetics could be incorporated in the human PBPK model. Model simulations
      demonstrate that especially in subjects with prolonged gastrointestinal residence
      times, GA may accumulate after repeated licorice consumption, thus increasing the
      health risk of this specific subgroup of individuals.

PMID- 11303963
TI  - Characteristics of choline transport across the blood-brain barrier in mice:
      correlation with in vitro data.
AB  - PURPOSE: We examined the functional properties of choline transport across the
      blood-brain barrier (BBB) in mice. We compared the kinetic parameters and
      transport properties with those found in our in vitro uptake experiments using
      mouse brain capillary endothelial cells (MBEC4). METHODS: The permeability
      coefficient-surface area product (PS) values of [3H]choline at the BBB were
      estimated by means of an in situ brain perfusion technique in mice. RESULTS:
      [3H]Choline uptake was well described by a two-component model: a saturable
      component and a nonsaturable linear component. The [3H]choline uptake was
      independent of pH and Na+, but was significantly decreased by the replacement of
      Na+ with K+. Various basic drugs, including substrates and inhibitors of the
      organic cation transporter, significantly inhibited the [3H]choline uptake. These
      in situ (in vivo) results corresponded well to the in vitro results and suggest
      that the choline transporter at the BBB is a member of the organic cation
      transporter (OCT) family. CONCLUSION: The choline transport mechanism at the BBB
      is retained in MBEC4.

PMID- 11303964
TI  - A population approach to enzyme characterization and identification: application
      to phenacetin O-deethylation.
AB  - PURPOSE: To determine the enzyme kinetics (EK) and identify the human
      cytochrome(s) P450 (CYP) involved in the deethylation of phenacetin to
      acetaminophen using a population-based method. METHODS: A sparse data set was
      generated from incubations containing human liver microsomes (n = 19) with
      phenacetin. Estimates of the EK parameters were obtained by fitting the
      concentration-velocity data to Michaelis-Menten models by using nonlinear mixed
      effects modeling. Relationships between the EK parameters and the CYP activities
      determined for these liver microsomes were examined. RESULTS: A two-enzyme
      kinetic model with a saturated, low KM enzyme and an unsaturated, high KM enzyme
      capable of forming acetaminophen best fit the data. The population estimates of
      the EK parameters were Vmax1, 911 pmol/min/mg protein; KM1, 11.3 microM; and
      Cl(int2), 0.4 microl/min/mg. The coefficients of variation for interliver
      variability in Vmax1 and residual error of the model were 39% and 15%,
      respectively. When the selective catalytic activities were examined as potential
      covariates, 7-ethoxyresorufin O-deethylation (CYP1A2) activity was found to be
      associated with the low KM enzyme, however, the high KM enzyme(s) could not be
      identified. CONCLUSIONS: The population approach characterized the EK parameters
      and identified the low KM enzyme responsible for phenacetin O-deethylation as
      CYP1A2. Population modeling of EK provides valuable information on inter- and
      intraliver variability in CYP dependent activities.

PMID- 11303965
TI  - Job matching in pharmacy labor markets: a study in four states.
AB  - PURPOSE: Reports from various pharmacy labor market sectors suggest that the
      United States may be experiencing a shortage of pharmacists. To guide policy
      making and planning with respect to this shortage, it is necessary to develop a
      better understanding of the process by which pharmacists choose jobs. Using the
      economic theory of job matching, this study sought to understand how (a)
      attributes of the practice setting, (b) characteristics of pharmacists, and (c)
      regional and urbanization variables are associated with pharmacy practice setting
      choices. METHODS: A secondary database containing information about employment
      characteristics and work histories of 541 pharmacists in four states was used.
      The data were augmented with information on the relative number of employment
      opportunities in each of three practice settings (large chain, institutional, and
      independent) in the year the respondent's most recent employment change occurred.
      Practice setting choices were modeled using multinomial conditional logit
      regression. RESULTS: A total of 477 pharmacists represented in the database met
      the inclusion criteria for the study. Multivariate analyses showed that the
      impact of search costs and wage differentials varied with the practice setting
      chosen. Pharmacists choosing independent settings over large chain settings were
      more likely to be white and to have worked in an independent setting in their
      prior job. Pharmacists living in Oregon were less likely to choose institutional
      settings compared to those living in Massachusetts, whereas those living in areas
      with populations greater than 50,000 were more likely to choose institutional
      settings. CONCLUSIONS: Pharmacist job matching appears to be a complex process in
      which diverse factors interact to produce a final match. Our results suggest that
      the pharmacy labor market may actually be composed of two distinct labor markets:
      an ambulatory market and an institutional market.

PMID- 11303966
TI  - Delivery of soluble tumor necrosis factor receptor from in-situ forming PLGA
      implants: in-vivo.

PMID- 11303967
TI  - Bioanalytical method validation--a revisit with a decade of progress.

PMID- 11303968
TI  - Gabexate mesilate in acute pancreatitis: miracle or mirage?

PMID- 11303969
TI  - Expression of proinflammatory and Th1 but not Th2 cytokines is enhanced in
      gastric mucosa of Helicobacter pylori infected children.
AB  - BACKGROUND: Helicobacter pylori-induced gastric inflammation is thought to be
      largely regulated by cytokines. PATIENTS AND METHODS: The expression of
      interferon-gamma, interleukin-12, interleukin-4, interleukin-10, interleukin-8,
      and interleukin-17 mRNA was examined on gastric mucosal samples from 24 children
      by semiquantitative reverse transcription polymerase chain reaction and southern
      blotting. Biopsy-based tests, serology, and urea 13C breath test were used to
      assess Helicobacter pylori status. Gastric biopsies were also evaluated for
      bacterial density, chronic inflammation, and acute inflammatory activity.
      RESULTS: Interferon-gamma, interleukin-12, interleukin-8 and interleukin-17
      expression was higher in Helicobacter pylori-infected (n=13) than uninfected
      (n=11) children. Conversely, interleukin-4 and interleukin-10 expression did not
      differ between Helicobacter pylori-infected and uninfected children. In
      Helicobacter pylori-infected children, interferon-gamma, interleukin-12,
      interleukin-8 and interleukin-17 expression correlated with bacterial density,
      and Interferon-gamma and interleukin-12 expression with chronic inflammation
      score. CONCLUSIONS: The findings of this study indicate that, in children,
      Helicobacter pylori-induced inflammatory response would favour production of
      proinflammatory cytokines and development of cell-mediated immunity, namely Th1
      response.

PMID- 11303970
TI  - Role of hepatitis viruses in multistep hepatocarcinogenesis.

PMID- 11303971
TI  - Increased prevalence of Helicobacter pylori in patients with diabetes mellitus.
AB  - BACKGROUND: Whilst upper gastrointestinal disturbances are frequently observed in
      patients with diabetes mellitus, little is known about the prevalence of
      Helicobacter pylori infection and peptic disease in these patients. AIM: To
      evaluate prevalence of Helicobacter pylori infection and peptic disease lesions
      in diabetics with dyspeptic symptoms. PATIENTS AND METHODS: Study population
      comprises 74 consecutive diabetes mellitus patients with dyspepsia and 117
      consecutive non diabetic dyspeptic patients. Upon enrolment, each patient
      completed an interview screening questionnaire to obtain information concerning
      presence and severity of dyspepsia. All patients underwent upper gastrointestinal
      endoscopy with biopsy specimens being collected from gastric antrum and body
      Helicobacter pylori was evaluated in each patient by rapid urease test and
      histology (Giemsa). Gastritis was classified according to the Sydney System.
      Statistical analysis was performed by chi-square, Fisher exact or t test and
      logistic regression analysis. A p value <0.05 was considered significant.
      RESULTS: Prevalence of Helicobacter pylori infection was found to be
      significantly higher in diabetics than in controls. The prevalence rate of
      endoscopic lesions was comparable in the two groups, but the association between
      endoscopic lesions and Helicobacter pylori infection was significantly higher in
      diabetics. Overall, the presence of chronic gastritis, both non atrophic and
      atrophic, as well as intestinal metaplasia were comparable in the two groups of
      patients, whilst the association between chronic gastritis and Helicobacter
      pylori infection or gastritis activity were significantly higher in diabetics. In
      neither group, was any correlation found between severity of dyspepsia and
      presence of endoscopic lesions, chronic gastritis or Helicobacter pylori
      infection. CONCLUSIONS: These data show a higher prevalence of Helicobacter
      pylori infection in diabetes mellitus patients with dyspepsia. Helicobacter
      pylori infection was significantly associated both with the presence of
      endoscopic lesions and chronic gastritis in diabetic patients, but not in the
      controls.

PMID- 11303972
TI  - Cut-off point, timing and pitfalls of the 13C-urea breath test as measured by
      infrared spectrometry.
AB  - BACKGROUND: The best timing and the best cut-off level of the 13C-urea breath
      test have not yet been well established. AIMS: To evaluate the cut-off value and
      the influence of medication on the 13C-urea breath test as measured by infrared
      spectrometry. METHODS: A series of 223 patients, sent for endoscopy performed 13C
      urea breath test in fasting conditions with 75 mg of 13C-urea and 20 ml of citric
      acid. Breath samples were collected before and then 10, 20, 25 and 30 minutes
      after ingestion. As gold standard, histological examination of gastric biopsies
      was used. A questionnaire was completed concerning the intake of medication,
      likely to influence the test, in the 2 months preceding the test. Sensitivity,
      specificity, positive predictive value and negative predictive value at 10, 20,
      25 and 30 minutes at different cut-off values (3, 3. 5, 4, 4. 5, 5.0 0/00 DOB]
      were calculated. RESULTS: A total of 182 patients did not take medication. There
      was no significant difference between the different cut-off levels at different
      times. Compared with the group of 41 patients who did take medication, likely to
      influence the test, the differences were significant (Fisher exact test).
      CONCLUSION: There was no significant difference between the different cut-off
      values. A 10-minute test with a cut-off level between 4 and 5% delta over
      baseline (sensitivity: 100%, specificity: 95%) is, therefore, proposed. To avoid
      false negative results due to unknown intake of medication, every patient
      submitted to the 13C-urea breath test should fill out a questionnaire.

PMID- 11303973
TI  - Low-amplitude propagated contractile waves: a relevant propulsive mechanism of
      human colon.
AB  - BACKGROUND: Human colonic motility is still poorly understood, especially as far
      as concerns its propulsive function. Available data refer almost exclusively to
      the forceful propulsive activity, which is recognized as high-amplitude
      propagated contractions, the manometric equivalent of mass movements. By
      contrast, information on less vigorous propulsive contractions is still lacking.
      AIMS: To investigate the presence and behaviour of low-amplitude propagated
      contractile waves (less than 50 mmHg in amplitude) in the colon of healthy humans
      during a 24-hour study period. SUBJECTS AND METHODS: A series of 16 healthy
      volunteers of both sexes entered the study, and were investigated by a standard
      technique involving a colonoscopically-positioned manometric catheter. During the
      study, two standard 1,000 kcal mixed meal and a 450 kcal breakfast were served.
      The recordings were, therefore, scanned for the presence of low-amplitude
      propagated contractile waves (waves of less than 50 mmHg in amplitude, propagated
      over at least three consecutive recording ports), their daily distribution, and
      their relationship with physiological events. RESULTS: Low-amplitude propagated
      contractile waves were constantly present in all the tracings, with an average of
      about 61 events/subject/day and a mean amplitude of about 20 mmHg. More than 80%
      of these events appeared during the day, with a significant (p<0.05) increase
      after meals and after morning awakening. In 25% of subjects, these waves were
      accompanied by emission of flatus. CONCLUSIONS: In the human colon, low-amplitude
      propagated contractile waves are a constant physiological propulsive pattern,
      which is generally related to sleep-wake cycles and meal ingestion.

PMID- 11303974
TI  - Bacterial infection in patients with advanced cirrhosis: a multicentre
      prospective study.
AB  - AIMS: To evaluate the prevalence, incidence and clinical relevance of bacterial
      infection in predominantly non-alcoholic cirrhotic patients hospitalised for
      decompensation. PATIENTS/METHODS: A total of 405 consecutive admissions in 361
      patients (249 males and 112 females; 66 Child-Pugh class B and 295 class C) were
      analysed. Blood, urine, ascitic and pleural fluid cultures were performed within
      the first 24 hours, during hospitalisation whenever infection was suspected, and
      again before discharge. RESULTS: Over a one year period, 150 (34%) bacterial
      infections (89 community- and 61 hospital-acquired) involving urinary tract
      (41%), ascites (23%), blood (21%) and respiratory tract (17%) were diagnosed. The
      prevalence of bacterial peritonitis was 12%. Infections were asymptomatic in 69
      cases (46%) and 130 (87%) involved a single site. Enteric flora accounted for 62%
      of infections, Escherichia Coli being the most frequent pathogen (25%). Community
      acquired infections were associated with more advanced liver disease (Child-Pugh
      mean score 10.2+/-2.1 versus 9.5+/-1.9, p<0.05), renal failure (p<0.05), and high
      white blood cell count (p<0.01). Hospital-acquired infections occurred more
      frequently in patients admitted for gastrointestinal bleeding (p<0.05). The in
      hospital mortality was significantly higher in infected than in non-infected
      patients (15% versus 7%, p<0.05), and infection emerged as an independent
      variable affecting survival. Moreover bacterial infection accounted for a
      significantly prolonged hospital stay. CONCLUSIONS: Bacterial infection,
      regardless of the aetiology, is a severe complication of decompensated cirrhosis,
      and, although frequently asymptomatic, accounts for both longer hospital stay and
      increased mortality.

PMID- 11303976
TI  - Antioxidant treatment in hereditary pancreatitis. A pilot study on three young
      patients.
AB  - BACKGROUND: Abdominal pain is the most challenging symptom of hereditary
      pancreatitis. No specific and proven therapy is yet available; analgesics, often
      in large doses, are required also in children and young patients. PATIENTS AND
      METHODS: We performed an open-label, pilot study on three young patients, coming
      from the same kindred, with hereditary pancreatitis. The study period lasted two
      years (July 1997-July 1999) and was divided into four sub-periods of six months
      each. In the first and third period the patients took only oral analgesics, if
      necessary; in the second and fourth period, an antioxidant regimen per os was
      added. This treatment consisted of sulphadenosyl-methionine (800 mg per day),
      Vitamin C (180 mg per day), Vitamin E (30 mg per day), Vitamin A (2,400 microg
      per day), and selenium (75 microg per day). RESULTS: Compliance of patients to
      the treatment schedule was satisfactory and no important side-effects were
      observed. Antioxidant treatment led to a significant reduction (p<0.05) in the
      number of days with abdominal pain experienced by the three patients and this was
      verified for both periods of treatment. Albeit, consumption of analgesics was
      lower in the antioxidant treatment periods. CONCLUSIONS: Oxidative stress may be
      one of the principle contributors to pain in hereditary pancreatitis and orally
      administered antioxidant treatment appears to be effective for control of the
      condition, in young patients, suffering from this rare disease.

PMID- 11303975
TI  - Multicentre comparative study of two schedules of gabexate mesilate in the
      treatment of acute pancreatitis. Italian Acute Pancreatitis Study Group.
AB  - AIM: To compare the efficacy of two different schedules of gabexate mesilate (900
      mg/day, or 1,500 mg/day) in the treatment of severe acute pancreatitis. SETTING:
      Forty-two Italian medical and surgical centres took part in the study. STUDY
      DESIGN: A multicentre, prospective, open label, comparative, parallel-group,
      randomized study. METHODS: The patients enrolled in the study had acute
      pancreatitis as demonstrated by typical abdominal pain and baseline serum amylase
      concentrations more than twice the upper normal limit, findings compatible with
      acute pancreatitis at imaging techniques, and a Glasgow criteria score of > or
      =3. Patients were randomly assigned to one of the two schedules of treatment with
      gabexate mesilate being administered intravenously for at least 7 days. The
      minimum clinically relevant difference (delta), between groups, in incidence of
      complications due to acute pancreatitis, during the first month of the study
      treatment, was predefined as equal to 10%. RESULTS: A total of 199 patients were
      assigned to gabexate mesilate 900 treatment and 189 to gabexate mesilate 1,500.
      Complications developed in 88 patients within one month of beginning treatment
      44/199: patients (22.1%) in the gabexate mesilate 900 group and 44/189 patients
      (23.3%) in the gabexate mesilate 1,500 group (difference 1.2%; 95% confidence
      interval: -7.2; 9.5%). CONCLUSIONS: Gabexate mesilate 900 mg per day is as
      effective as gabexate mesilate 1,500 mg per day in reducing the complications due
      to acute pancreatitis.

PMID- 11303977
TI  - Intestinal tuberculosis as a cause of chronic diarrhoea among patients with human
      immunodeficiency virus infection: report of two cases.
AB  - In Western countries human immunodeficiency virus infection is considered the
      main risk factor of tuberculous disease, its incidence being 500 times higher in
      HIV-infected patients than in the general population. Despite the disease
      frequently present in these patients with extraintestinal manifestations,
      intestinal localization is rarely observed and often as a consequence of
      complications such as acute gastrointestinal bleeding or perforation. The
      diagnosis of intestinal tuberculosis is difficult and is often delayed due to the
      lack of specific signs and symptoms as well as the low sensitivity of routine
      methods. A review of the literature is made and personal experience in the
      diagnosis of two cases is reported.

PMID- 11303979
TI  - Gastric mucosal immune response in Helicobacter pylori infection in children. Men
      are not mice and more paediatric studies are needed.

PMID- 11303978
TI  - Carbonic anhydrase isozymes in the human pancreas.
AB  - Recently, an increasing number of carbonic anhydrase (CA) isozymes have been
      discovered in the human pancreas. These isozymes are classified as the CA family
      with various molecular structures and different subcellular localizations:
      cytoplasmic CA II, mitochondrial CA VB, secretory CA VI, membrane-bound CA IV,
      and transmembrane CA IX and XII. However, there is little evidence concerning
      their pathophysiological roles. Here, we reviewed the expression of CA isozymes
      in the human pancreas and proposed hypotheses related to their physiological and
      pathological roles.

PMID- 11303980
TI  - "Cervia Working Group Report": guidelines on the diagnosis and treatment of
      Helicobacter pylori infection.
AB  - Different national attitudes exist between countries in Europe concerning
      eradication of Helicobacter pylori infection due to the wide differences in
      Helicobacter pylori prevalence, gastric cancer risk, bacterial resistance to
      antibiotics, health care systems and financial resources. The Cervia Working
      Group Report has been established in order to fill the gap in the absence of
      National Guidelines in Italy concerning the diagnosis and treatment of
      Helicobacter pylori infection. The recommendations made are, by and large,
      similar to the European Guidelines but differ slightly with regard to the "test
      and-treat" approach to young dyspeptics without sinister symptoms. In the absence
      of a national validation of this strategy a case-by-case assessment of dyspepsia
      has been promoted, both at primary care and specialist level. Another area of
      partial disagreement concerns the eradication of Helicobacter pylori in patients
      undergoing long-term proton pump inhibitor treatment which has not been generally
      recommended as scientific evidence in support of this policy is at present rather
      weak.

PMID- 11303981
TI  - Hepatic iron storage and megamitochondria formation in patients with chronic
      hepatitis C related to the hepatitis C virus genotype.

PMID- 11303982
TI  - Recurrent abdominal pain in Malaysian children: clinical profiles and outcome.

PMID- 11303983
TI  - Open access upper gastrointestinal endoscopy.

PMID- 11303984
TI  - Mixed hyperplastic adenomatous polyps: neoplastic transformation of hyperplastic
      colorectal polyps?

PMID- 11303985
TI  - Concurrent non-alcoholic steatohepatitis and psoriasis. Report of three cases
      from the POLI.ST.E.N.A. study.

PMID- 11303986
TI  - Frequency of colorectal cancer in patients with iron deficiency anaemia.

PMID- 11303987
TI  - Bacterial infections in patients with cirrhosis: reasons, comments and
      suggestions.

PMID- 11303988
TI  - 2000 SLS Presidential Address.

PMID- 11303989
TI  - Laparoscopy in patients with prior surgery: results of the blind approach.
AB  - BACKGROUND AND OBJECTIVES: To compare the complication rate due to blind access
      laparoscopy between patients with or without a prior history of laparotomy.
      METHODS: We examined a prospective record of data on laparoscopic surgeries
      performed from 1992 to 1998. Only cases in which the Veress needle and the first
      trocar were inserted through the umbilicus were included in this study. Results
      issued from patients without previous abdominal surgery (Group I) were compared
      with those arising from women with prior laparotomy (Group II). A statistical
      analysis was performed using the Chi-square test or Fisher exact test when
      appropriate. RESULTS: One thousand thirty-three laparoscopies were carried out
      during the study period, 881 of which began with a blind access through the
      umbilicus. Two hundred two women (19.3%) had an history of abdominal or pelvic
      surgery. Eight hundred forty-two patients were included in Group I and 39 in
      Group II. Failure to penetrate into the peritoneal cavity occurred significantly
      more frequently in Group II (4/39) than in Group I (1/842, P < 0.0001). The
      insertion of the Veress needle gave rise to 2 complications in Group I and 0 in
      Group II (P = 1.0). Transumbilical trocar insertion gave rise to 1 complication
      in each group (1/841 vs. 1/35, P = 0.11). When all events were considered,
      incidents or accidents were significantly more frequent in Group II (5/39) than
      in Group I (4/842)(P < 0.0001). CONCLUSIONS: We recorded a higher rate of
      incidents/complications due to the Veress needle and trocar insertion in patients
      with a previous history of laparotomy. An adapted approach should be recommended
      for these patients.

PMID- 11303990
TI  - Laparoscopic intracorporeal bowel resection with ultrasound versus
      electrosurgical dissection.
AB  - BACKGROUND AND OBJECTIVES: We assessed resection time and collateral thermal
      tissue damage of ultrasonically activated surgery (UAS) and high-frequency blade
      enhanced bipolar electrosurgery (BE) in laparoscopic bowel surgery. METHODS: We
      compared UAS laparoscopic intracorporeal small bowel mesentery re-section with an
      equivalent procedure performed with BE in a porcine model. Resection was defined
      as 12 end-arcade arteries supplying the intended bowel segment. Vessels were
      divided one cm off the bowel wall. Aside from shaft diameter, jaws gaping
      pattern, and cutting blade length, UAS and BE devices were well matched for
      handle ergonomics, jaws gaping extent, power setting, type of use, working shaft
      axial rotation, and length. A pathologist blind to the method used assessed the
      collateral thermal damage. Resections were allocated to either method by computer
      generated block randomization. The study design was sequential triangular with a
      5% significance level and 90% power. RESULTS: No significant differences occurred
      in intraoperative blood pressure and heart rate variations in pigs undergoing UAS
      or BE. Median operating time (measured after 10, 20, and 30 resections in each
      study arm) was significantly shorter in UAS than in BS (0.57 vs. 2.01 min P <
      0.001). Histology of small bowel wall specimens revealed no collateral thermal
      damage. CONCLUSIONS: UAS laparoscopic bowel surgery offers reduced resection time
      as com-pared with its BE counterpart in a porcine model.

PMID- 11303991
TI  - The success of laser laparoscopy in the treatment of endometriosis: a two-step
      analysis.
AB  - BACKGROUND AND OBJECTIVES: The most advantageous treatment for nonextensive
      endometriosis has long been the subject of debate. In recent years, the ability
      to detect atypical presentations has allowed the gynecological surgeon to treat
      this disease more readily. The treatment in the past has only been concerned with
      the singular treatment being applied at the time, not on the effects that
      previous treatments have had. The purpose of the current study was to see whether
      previous unsuccessful treatment modalities affected subsequent laser laparoscopy
      treatment of endometriosis. METHODS: Patients who were previously treated for
      their endometriosis (minimal and mild) underwent treatment of their disease by
      laser laparoscopy and the results were analyzed by chi2 (chi-square) analysis.
      RESULTS: Those patients previously treated with laser laparoscopy and laparotomy
      demonstrated poorer results than those previously treated with expectant,
      medical, or cautery. The sum of the original treatments plus the second treatment
      of laser laparoscopy was equal in all groups. CONCLUSIONS: If endometriosis is
      diagnosed at the time of laparoscopy and is easily amenable to treatment, it
      behooves the physician to treat it at the time of surgery.

PMID- 11303992
TI  - Vaginal vault suspension and enterocele repair by Richardson-Saye laparoscopic
      technique: description of training technique and results.
AB  - OBJECTIVES: To describe the Richardson-Saye technique for laparoscopic vaginal
      vault suspension and enterocele repair (vaginal apex reconstruction) and the
      appropriate training needed for performance of this technique. METHODS: Before
      using this technique, Drs Carter, Winter, and Mendelsohn first received training
      by observation of skilled surgeons performing the procedure, attending courses,
      and finally being tutored and proctored by Dr Saye on the appropriate performance
      of the technique. They then used this technique to surgically treat eight
      patients, 42 to 85 years of age, mean age 62 years, between March and September
      of 1999. RESULTS: We included eight patients in this study who underwent the Saye
      Richardson vaginal vault suspension and enterocele repair (apical vaginal vault
      reconstruction) by the suture technique. In all patients at six-month follow-up,
      the vaginal apex remains intact and well supported. We describe here the entire
      vaginal vault suspension and enterocele repair procedure with all its relevant
      details. CONCLUSION: Laparoscopic reconstruction of the disrupted vaginal apex
      followed by reattachment to the previously broken uterosacral ligament with the
      use of permanent suture provides a secure and anatomically correct vault
      suspension. Before performing this technique, physicians should undergo proper
      training, including observation, courses, tutoring, and proctorship by a surgeon
      experienced in performing this technique.

PMID- 11303993
TI  - Saphenous vein endothelial cell viability: a comparative study of endoscopic and
      open saphenectomy for coronary artery bypass grafting.
AB  - BACKGROUND: The use of endoscopic saphenous vein harvesting (ESVH) for coronary
      artery bypass grafting (CABG) is growing. This study was done to investigate the
      extent of endothelial injury in ESVH compared with that of the standard open
      method (OSVH), and under various physical and chemical preservation factors.
      METHODS: We endoscopically removed the saphenous vein from 45 consecutive
      patients undergoing saphenectomy for CABG together with a segment retrieved by
      the no-touch OSVH method. Vein samples from each group were divided into 8
      subgroups of 5 samples each, and incubated in Plasma-Lyte solution with or
      without papaverine, at distending pressures of 100 or 300 mm Hg, and at either 4
      degrees C or 28 degrees C, respectively. A ninth subgroup was preserved at room
      temperature without pressure or papaverine. The viability of cultured saphenous
      vein endothelial cells was assessed by counting the number of total cells and
      deriving the proportion of viable cells, following incubation for 72 hours.
      RESULTS: The median proportion of viable cells (PVC) showed a slight decline over
      days 0 to 4 for both harvesting methods. No significant difference existed in the
      median PVC between the two techniques (day 0: 75%, 72%, P = 0.8; day 1: 66.7%,
      66.7%, P = 0.9; day 2: 66.7%, 66.7%, P = 0.3; day 3: 65.3%, 66.7%, P = 0.16,
      respectively). The mean PVC compared across temperatures of 4 degrees C, 28
      degrees C, and room temperature for the ESVH was highly significant, with the
      highest value being for room temperature (69.5%, 56.4%, 70.3%, respectively, P =
      0.0003). Results for the OSVH were not significant. The effect of distension
      pressure did not vary significantly for 0, 100, and 300 mm Hg for both techniques
      (70.3%, 63.2% and 63.4%, respectively, P = 0.46 for the ESVH; 66.5%, 68.4%,
      67.4%, respectively, P = 0.94 for the OSVH). The addition of papaverine improved
      PCV slightly for the OSVH only (61.7%, 64.3%, respectively, P = 0.02), whereas
      that for the ESVH was not significant (67.3%, 72.5%, P = 0.12). CONCLUSION: The
      effect of ESVH on endothelial cell viability is comparable to that of the OSVH.
      Among the factors influencing endothelial viability during vein preparation,
      temperature had a major effect with lower temperatures in the range of 4 degrees
      C to room temperature being the most favorable one. Mechanical distension and
      papaverine had unimportant or inconsistent roles. We recommend the ESVH as the
      procedure of choice for saphenous vein harvesting due to the lower postoperative
      morbidity, and the lower incubation temperature needed for its better influence
      on potential graft patency.

PMID- 11303994
TI  - Comparison of laparoscopic-assisted appendectomy with intracorporal laparoscopic
      appendectomy and open appendectomy.
AB  - BACKGROUND: A laparoscopic appendectomy is associated with less postoperative
      pain and a shorter postoperative stay than the open technique. However, the open
      technique is faster and less expensive than the completely laparoscopic method. A
      laparoscopic-assisted appendectomy has the advantages of both the laparoscopic
      and open techniques. METHODS: A retrospective study involving 83 patients was
      performed comparing the three different techniques. The comparison studied
      operating time, surgical expense, and postoperative stay. RESULTS: The completely
      laparoscopic method was performed on 24 patients with an average surgical time of
      88.9 minutes, average charges of $604, and average postoperative stay of 2.6
      days. The open technique was performed on 26 patients with a surgical time of
      77.1 minutes, charges of $42, and a postoperative stay of 2.4 days. The
      laparoscopic-assisted technique was performed on 33 patients with a surgical time
      of 70.3 minutes, charges of $208, and a postoperative stay of 1.8 days.
      CONCLUSION: The laparoscopic-assisted method of appendix removal can be performed
      as efficiently as the open technique but at <67% of the cost of the complete
      laparoscopic method. The postoperative stay is shorter for the laparoscopic
      assisted technique than for the open technique. Thus, the laparoscopic-assisted
      technique is a cost-effective method for removing the appendix.

PMID- 11303995
TI  - Report of laparoscopic cholecystectomy in two patients with left-sided
      gallbladders.
AB  - Laparoscopic cholecystectomy has been widely performed since its introduction in
      1987 by Mouret. However, conversion to open cholecystectomy is common when the
      surgeon encounters variant anatomy. We report 2 cases of cholecystitis and
      cholelithiasis in patients with left-sided gallbladders that were treated with
      laparoscopic cholecystectomy by the same surgeon at this institution. The patient
      in the first case had the condition of situs inversus totalis, and the
      gallbladder of the second patient was located to the left of the round ligament.
      In both instances, successful laparoscopic cholecystectomy was performed, and the
      patients recovered uneventfully.

PMID- 11303996
TI  - Pseudoachalasia as a result of metastatic cervical cancer.
AB  - BACKGROUND: Distinguishing achalasia from pseudoachalasia can be difficult, as
      the clinical, radiological, and manometric findings can be similar to those seen
      in achalasia. The features that may differentiate achalasia from pseudoachalasia
      are reviewed and the pathogenesis of pseudoachalasia is discussed. METHODS: A
      patient presented with a clinical scenario of achalasia that was documented by
      radiographic, endoscopic, and manometric studies. Her past medical history was
      significant for cervical cancer. Although brief improvement in symptoms was
      achieved with botulinum toxin injections and esophageal dilation, she had
      continued progression of symptoms. This direct involvement of the esophagus by a
      tumor was not demonstrated by any of the routine preoperative studies. RESULTS:
      At the time of surgery, extensive involvement of the diaphragm, esophagus, and
      pericardium by a tumor was noted. Pathologic analysis of the tumor was consistent
      with metastatic cervical cancer CONCLUSION: Pseudoachalasia has been known to
      occur in response to both benign and malignant causes. Differentiating between
      pseudoachalasia and achalasia is often difficult because of the similarities. As
      in this case, the diagnosis of pseudoachalasia may be made by surgical
      exploration.

PMID- 11303997
TI  - Immune thrombocytopenic purpura during pregnancy: laparoscopic treatment.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic surgical techniques in pregnancy have
      been accepted and pose minimal risks to the patient and fetus. We present the
      first reported case of a pregnant woman with immune thrombocytopenia purpura who
      underwent laparoscopic splenectomy during the second trimester. METHODS AND
      RESULTS: The anesthesia, hematology, and obstetrics services closely followed the
      patient's preoperative and intraoperative courses. After receiving immunization,
      stress close steroids, and prophylactic antibiotics, she underwent a successful
      laparoscopic splenectomy. After a short hospital stay, the patient was discharged
      home. CONCLUSION: Immune thrombocytopenia purpura can be an indication for
      splenectomy. As demonstrated in appendectomy, cholecystectomy, and our case
      presentation, laparoscopic splenectomy can be safely performed during pregnancy.

PMID- 11303998
TI  - Culdolaparoscopy: a preliminary report.
AB  - OBJECTIVE: To introduce a surgical technique that combines culdoscopy with
      laparoscopy and microlaparoscopy. METHODS: This was a feasibility study conducted
      at The Mount Sinai Hospital of Queens. The technique is used when a larger port
      is required during laparoscopy or microlaparoscopy procedures. The additional
      port is placed in the vagina and, under laparoscopic surveillance, into the
      posterior cul-de-sac. RESULTS: This operation has been performed successfully in
      5 oophorectomies, 4 myomectomies, 3 salpingoophorectomies, and 1 salpingectomy.
      CONCLUSION: This technique reduces the need for abdominal ports in excess of 5
      mm. These ports can have a visual or operative function depending on the nature
      or stage of the procedure. The vaginal port can serve a visual function similar
      to that of culdoscopy or may be used for the introduction of operative
      instruments and the extraction of specimens. A principal benefit of using the
      larger vaginal port is derived from the capability of assisting laparoscopy and
      allowing the surgeon to use fewer and smaller abdominal trocars.

PMID- 11303999
TI  - Ergonomics: requirements for adjusting the height of laparoscopic operating
      tables.
AB  - BACKGROUND AND OBJECTIVES: In the last few years many new instruments and devices
      have been developed and introduced into the operating room (OR). A debate has
      been ongoing about the optimal ergonomic posture for the operating staff. From
      practical experience, we have learned that the operating tables cannot be
      adjusted adequately to allow surgeons of different stature to maintain a
      comfortable posture. The goal of this study was to establish the most ergonomic
      table height for the particular physique of the surgeon and the different types
      of laparoscopic instrument handles that he or she uses. METHODS: In a simulated
      model, two probands of different stature (50th [BS 50] and 95th [BS 95]
      percentile) used laparoscopic instruments with four different handle designs
      (shank, pistol, axial, and rod). The instruments were inserted into a board in
      three different angles ([IA] = 20 degrees, 30 degrees, 40 degrees). Additionally
      the elbow angles (EA) of the volunteers were fixed to either 90 degrees or 120
      degrees. For every variable (size of surgeon and his or her elbow angle, design
      of handle, insertion angle of the instrument) the height of the board, as a
      parameter for the level of the abdominal wall of a patient with
      pneumoperitioneum, was measured from the floor. RESULTS: All parameters had an
      effect on the optimal operating table height. The lowest required operating table
      level was 30 cm, the highest was 60.5 cm. In laparoscopic surgery-long shafted
      instruments and patients with pneumoperitoneum-the tabletops are too high for
      over 95% of all surgeons. As skin incision and wound suture are performed the
      conventional way, the operating tabletop must be adjustable up to the common
      height of 122 cm. The maximal difference between the optimal heights of the OR
      table for one volunteer using two different handles with different insertion
      angles of the instruments (BS 95, EA 90 degrees, IA 20 degrees, rod handle to BS
      50, EA 120 degrees, IA 40 degrees, axial handle) was about 27 cm. CONCLUSION: New
      operating tables with a much lower adjustability are necessary to fulfill
      ergonomic requirements. The use of differently designed handles can hinder the
      ergonomic posture of the surgeon, because each handle requires a different
      working height.

PMID- 11304000
TI  - Laparoscopic treatment of two patients with omental infarction mimicking acute
      appendicitis.
AB  - BACKGROUND: Omental infarction is a rare entity that usually causes symptoms
      similar to those of appendicitis. Ultrasound or computerized tomography scan can
      diagnose omental infarction preoperatively. METHODS: We treated two patients with
      omental infarction by performing a laparoscopic omentectomy in each one. RESULTS:
      The pathology verified the operative diagnosis, and both patients were discharged
      home on the first postoperative day. CONCLUSION: Omental infarction can be
      accurately diagnosed and safely treated with laparoscopy. Key Words: Laparoscopy,
      Omental infarction, Acute abdominal pain.

PMID- 11304001
TI  - Urologic complication of laparoscopic appendectomy.
AB  - Abscess formation after a ruptured appendix is a well-known phenomenon. Extra
      abdominal complications are somewhat rare. Here we present an unusual urologic
      complication in a case of a perforated appendix and abdominal sepsis.

PMID- 11304002
TI  - Laparoscopic-assisted vaginal myomectomy: a case report and literature review.
AB  - The purpose of this article is to present a case of laparoscopic myomectomy (LM)
      that led to the identification of a new minimally invasive technique
      [laparoscopic-assisted vaginal myomectomy (LAVM)] for removing multiple
      transmural uterine myomas and facilitating uterine suturing. In addition, we
      reviewed the literature to (1) describe the history leading up to LAVM, (2)
      relate the benefits of this technique to other more widely performed myomectomy
      procedures [LM and laparoscopic-assisted myomectomy (LAM)], and (3) identify
      criteria for LM and LAVM.

PMID- 11304003
TI  - Operative laparoscopy and vulvar hematoma: an unusual association.
AB  - Few cases of intraoperative or postoperative complications associated with
      laparoscopic adnexal surgery have been reported in the literature. We describe a
      case of laparoscopic abdominal vascular injury and persistent bleeding in the
      matrix of the ovary following laparoscopic cystectomy. During the first
      postsurgical day, the patient was syncopal. The physical examination showed a
      vulvar hematoma and minimal bleeding from a laparoscopic incision in the
      abdominal wall. Vulvar hematoma and an unstable patient may signal serious
      vascular bleeding.

PMID- 11304004
TI  - The first laparoscopic cholecystectomy.
AB  - Prof Dr Med Erich Muhe of Boblingen, Germany, performed the first laparoscopic
      cholecystectomy on September 12, 1985. The German Surgical Society rejected Muhe
      in 1986 after he reported that he had performed the first laparoscopic
      cholecystectomy, yet in 1992 he received their highest award, the German Surgical
      Society Anniversary Award. In 1990 in Atlanta, at the Society of American
      Gastrointestinal Surgeons (SAGES) Convention, Perissat, Berci, Cuschieri, Dubois,
      and Mouret were recognized by SAGES for performing early laparoscopic
      cholecystectomies, but Muhe was not. However, in 1999 he was recognized by SAGES
      for having performed the first laparoscopic cholecystectomy-SAGES invited Muhe to
      present the Storz Lecture. In Muhe's presentation, titled "The First Laparoscopic
      Cholecystectomy," which he gave in March 1999 in San Antonio, Texas, he described
      the first procedure. Finally, Muhe had received the worldwide acclaim that he
      deserved for his pioneering work. One purpose of this article is to trace the
      development of the basic instruments used in laparoscopic cholecystectomy. The
      other purpose is to give Muhe the recognition he deserves for being the developer
      of the laparoscopic cholecystectomy procedure.

PMID- 11304005
TI  - Laparoscopic surgery: an evolving revolution.

PMID- 11304006
TI  - Combining myoma coagulation with endometrial ablation/resection reduces
      subsequent surgery rates.

PMID- 11304007
TI  - Distance perception mediated through nested contact relations among surfaces.
AB  - In complex natural scenes, objects at different spatial locations can usually be
      related to each other through nested contact relations among adjoining surfaces.
      Our research asks how well human observers, under monocular static viewing
      conditions, are able to utilize this information in distance perception. We
      present computer-generated naturalistic scenes of a cube resting on a platform,
      which is in turn resting on the ground. Observers adjust the location of a marker
      on the ground to equal the perceived distance of the cube. We find that (1)
      perceived distance of the cube varies appropriately as the perceived location of
      contact between the platform and the ground varies; (2) variability increases
      systematically as the relating surfaces move apart; and (3) certain local edge
      alignments allow precise propagation of distance information. These results
      demonstrate considerable efficiency in the mediation of distance perception
      through nested contact relations among surfaces.

PMID- 11304008
TI  - Perceptual completion in rhesus monkeys (Macaca mulatta) and pigeons (Columbia
      livia).
AB  - In a two-dimensional drawing, when the narrow edge of a bar appears to touch the
      edge of a large rectangle, humans overestimate the length of the bar (Kanizsa,
      1979). Kanizsa has suggested that this illusion occurs because humans perceive
      the bar as continuing behind the rectangle and complete the "occluded" portion of
      the bar. Rhesus monkeys and pigeons were trained to classify black target bars
      with a variety of lengths as "long" or "short." In training, the bar was always
      located at the same distance from a gray box. After learning this discrimination,
      the subjects were tested on novel stimuli, in which the bar was located at three
      new locations. Monkeys showed a consistent response bias for "long" when the bar
      touched the box, but pigeons did not. Monkeys appear to have completed the
      "occluded" part like humans, whereas pigeons failed to do so. Because this
      procedure does not require animals to complete the "occluded" part with any
      particular form, their failure suggests that pigeons do not even perceive the
      target bar as continuing behind the "occluding" figure. The failure of pigeons
      may be due to difficulty in perceiving depth from two-dimensional drawings.

PMID- 11304009
TI  - A two-stage model for visual-auditory interaction in saccadic latencies.
AB  - In two experiments, saccadic response time (SRT) for eye movements toward visual
      target stimuli at different horizontal positions was measured under simultaneous
      or near-simultaneous presentation of an auditory nontarget (distractor). The
      horizontal position of the auditory signal was varied, using a virtual auditory
      environment setup. Mean SRT to a visual target increased with distance to the
      auditory nontarget and with delay of the onset of the auditory signal relative to
      the onset of the visual stimulus. A stochastic model is presented that
      distinguishes a peripheral processing stage with separate parallel activation by
      visual and auditory information from a central processing stage at which
      intersensory integration takes place. Two model versions differing with respect
      to the role of the auditory distractors are tested against the SRT data.

PMID- 11304010
TI  - Temporal processing ability in above average and average readers.
AB  - In the present study, we compared the rapid visual and auditory temporal
      processing ability of above average and average readers. One hundred five
      undergraduates participated in various visual and auditory temporal tasks. The
      above average readers exhibited lower auditory and visual temporal resolution
      thresholds than did the average readers, but only the differences in the auditory
      tasks were statistically significant, especially when nonverbal IQ was controlled
      for. Furthermore, both the correlation and stepwise multiple regression analyses
      revealed a relationship between the auditory measures and the wide range
      achievement test (WRAT) reading measure and a relationship between the auditory
      measures and a low spatial frequency visual measure and the WRAT spelling
      measure. Discriminant analysis showed that together both the visual and auditory
      measures correctly classified 75% of the subjects into above average and average
      reading groups, respectively. The results suggest that differences in temporal
      processing ability in relation to differences in reading proficiency are not
      confined to the comparison between poor and normal readers.

PMID- 11304011
TI  - An explanation of orthogonal S-R compatibility effects that vary with hand or
      response position: the end-state comfort hypothesis.
AB  - This study presents an explanation of orthogonal stimulus-response compatibility
      (SRC) effects that vary with hand or response location: the end-state comfort
      hypothesis. It posits that responses are spatially transformed and cognitively
      mapped onto the stimulus dimension according to relative hand posture, thereby
      mediating the pattern of facilitation and interference in response selection. In
      the first three experiments, we investigated the eccentricity effect, finding
      that responses by the left hand in left hemispace are faster with up-left/down
      right mapping while responses by the right hand in right hemispace are faster
      with up-right/down-left mapping (Michaels & Schilder, 1991, Experiment 1). The
      endstate comfort hypothesis correctly predicted that the eccentricity effect
      occurred irrespective of the relative position of the stimulus and response
      device in the sagittal plane (Experiments 1 and 2), and that it reversed when the
      stimulus-response set was reversed, regardless of the relative position of the
      stimulus and response device in the fronto-parallel plane (Experiments 2 and 3).
      Experiment 4 shows a new orthogonal SRC effect that was predicted by the end
      state comfort hypothesis. Our results are inconsis tent with other explanations,
      such as the virtual-lines hypothesis and the salient-features hypothesis.

PMID- 11304012
TI  - Postcoincidence trajectory duration affects motion event perception.
AB  - In a two-dimensional display, identical visual targets moving toward and across
      each other with equal, constant speed can be perceived either to reverse their
      motion directions at the coincidence point (bouncing percept) or to stream
      through one another (streaming percept). Although there is a strong tendency to
      perceive the streaming percept, various factors have been reported to induce the
      bouncing percept, such as a sound or a visual flash at the moment of the visual
      target coincidence. By changing duration of the postcoincidence trajectory (PCT),
      we investigated how long it would take for such bounce-inducing factors to be
      maximally effective after the visual coincidence. With bounce-inducing factors,
      the percentage of the bouncing percept did not reach its maximal level
      immediately after the coincidence but increased as a function of PCT duration up
      to 150-200 msec. The results clearly reject the possibility of the cognitive-bias
      hypothesis about the bounce-inducing effect and suggest rather that the bounce
      inducing factors have to interact with the PCT for some period after the
      coincidence to be maximally effective.

PMID- 11304013
TI  - Detection of acoustic repetition for very long stochastic patterns.
AB  - Guttman and Julesz (1963) employed recycling frozen noise segments (RFNs) as
      model stimuli in their classic study of the lower limits for periodicity
      detection and short-term auditory memory. They reported that listeners can hear
      iteration of these stochastic signals effortlessly as "motorboating" for
      repetition periods ranging from 50 to 250 msec and as "whooshing" from 250 msec
      to 1 sec. Both motorboating and whooshing RFNs are global percepts encompassing
      the entire period, as are RFNs in the pitch range (repetition periods shorter
      than 50 msec). However, with continued listening to whooshing (but not
      motorboating) RFNs, individuals hear recurrent brief components such as clanks
      and thumps that are characteristic of the particular waveform. Experiment 1 of
      the present study describes a cross-modal cuing procedure that enables listeners
      to store and then recognize the recurrence of portions of frozen noise waveforms
      that are repeated after intervals of 10 sec or more. Experiment 2 compares the
      relative saliencies of different spectral regions in enabling listeners to detect
      repetition of these long-period patterns. Special difficulty was encountered with
      the 6-kHz band of RFNs, possibly due to the lack of fine-structure phase locking
      at this frequency range. In addition, a similarity is noted between the
      organizational principles operating over particular durational ranges of
      stochastic patterns and the characteristics of traditional hierarchical units of
      speech having corresponding durations.

PMID- 11304014
TI  - Effects of gravitational and optical stimulation on the perception of target
      elevation.
AB  - To examine the combined effects of gravitational and optical stimulation on
      perceived target elevation, we independently altered gravitational-inertial force
      and both the orientation and the structure of a background visual array. While
      being exposed to 1.0, 1.5, or 2.0 Gz in the human centrifuge at NASA Ames
      Research Center, observers attempted to set a target to the apparent horizon. The
      target was viewed against the far wall of a box that was pitched at various
      angles. The box was brightly illuminated, had only its interior edges dimly
      illuminated, or was kept dark. Observers lowered their target settings as Gz was
      increased; this effect was weakened when the box was illuminated. Also, when the
      box was visible, settings were displaced in the same direction as that in which
      the box was pitched. We attribute our results to the combined influence of
      otolith-oculomotor mechanisms that underlie the elevator illusion and visual
      oculomotor mechanisms (optostatic responses) that underlie the perceptual effects
      of viewing pitched visual arrays.

PMID- 11304015
TI  - Effects of supine body position and low radial accelerations on the visually
      perceived apparent zenith.
AB  - The visually perceived eye level (VPEL) has been shown to shift toward the lower
      part of the body in upright subjects facing toward the axis of rotation on a
      centrifuge. This shift occurs in the same direction as the shift in the gravito
      inertial forces (Gis) produced by very low radial acceleration (centrifugation)
      combined with gravity. The purpose of this study was to determine whether the
      same phenomenon affects the visually perceived apparent zenith (VPAZ) in subjects
      in a supine position. Twelve supine subjects were instructed to set a luminous
      target to the VPAZ, either while they were in total darkness and motionless or
      while undergoing very low centrifugation. Data showed that Gis induced a VPAZ
      shift similar to that observed for the VPEL. Thus, as is the case for the VPEL,
      the corresponding logarithmic psychophysical function of the VPAZ may be
      considered to be a type of oculogravic illusion phenomenon with differences in
      the subjects' that differs from subject to subject, depending on the subject's
      sensitivity to low radial accelerations. Data on VPEL and VPAZ support the notion
      that the subjective perception of eye level in total darkness takes into account
      changes--even if extremely slight-in the direction of the gravito-inertial forces
      produced by the combination of gravity and low radial accelerations, although
      subjects are unaware of the Gi shift. However, depending on the intensity of the
      radial acceleration and the angular deviation of Gi relative to G, the shift of
      the VPEL and the VPAZ can be either amplified or attenuated. Moreover,
      differences between VPEL and VPAZ responses suggest two explanatory assumptions-
      namely, that this is (1) a peripheral phenomenon dependent on the
      neurophysiological anisotropy of the otolithic system or (2) a central phenomenon
      dependent on the relevance assigned to the peripheral information by the
      integrative sensory functions and the associative processes.

PMID- 11304016
TI  - Effect of visual surrounding motion on body sway in a three-dimensional
      environment.
AB  - Unidirectional motion of a uniplanar background induces a codirectional postural
      sway. It has been shown recently that fixation of a stationary foreground object
      induces a sway response in the opposite direction (Bronstein & Buckwell, 1997)
      when the background moves transiently. The present study investigated factors
      determining this contradirectional postural response. In the experiments
      presented, center of foot pressure and head displacements were recorded from
      normal subjects. The subjects faced a visual background of 2 x 3 m, at a distance
      of 1.5 m, which could be moved parallel to the interaural axis. Results showed
      that when the visual scene consisted solely of a moving background, the
      conventional codirectional postural response was elicited. When subjects were
      asked to fixate an earth-fixed foreground (window frame) placed between them and
      the moving background, a consistent postural response in the opposite direction
      to background motion was observed. In addition, we showed that this
      contradirectional postural response was not transient but was sustained for the
      11 sec of background motion. We investigated whether this contradirectional
      postural response was the consequence of the induced movement of the foreground
      by background motion. Although induced movement was verbally reported by subjects
      when viewing an earth-fixed target projected onto the moving background, the
      contradirectional sway did not occur. These results indicate that foreground
      background separation in depth was necessary for the contradirectional postural
      response to occur rather than induced movement. Another experiment showed that,
      when the fixated foreground was attached to the head of the observer, the
      contradirectional sway was not observed and was therefore unrelated to vergence.
      Finally, results showed that the contradirectional postural response was, in the
      main, monocularly mediated. We conclude that the direction of the postural sway
      produced by a moving background in a three-dimensional environment is determined
      primarily by motion parallax.

PMID- 11304017
TI  - Visual marking and the perception of salience in visual search.
AB  - In the present study, the gap paradigm originally developed by Watson and
      Humphreys (1997) was used to investigate whether the process of visual marking
      can influence the perceptual salience of a target in visual search. Consistent
      with previous studies (Watson & Humphreys, 1997), the results showed that search
      was not affected by the presence of the preceding distractors when the target was
      relatively low in salience. This finding suggests that visual marking can
      increase the efficiency of visual search by decreasing the size of the search
      set. However, more important, the results also showed that search was affected by
      the presence of the preceding distractors when the target was relatively high in
      salience. This finding suggests that visual marking may be limited in its ability
      to increase the perceptual salience of the target. Together, the results of the
      present study suggest that the effectiveness of visual marking may vary as a
      function of search context.

PMID- 11304018
TI  - Visual marking in moving displays: feature-based inhibition is not necessary.
AB  - Visual marking is a mechanism by which new visual stimuli can gain a selection
      advantage by the top-down attentional inhibition of stimuli already in the field.
      Previous work (Olivers, Watson, & Humphreys, 1999) has shown that, for moving
      stimuli, there must be a unique feature difference between the old items and the
      new items for marking to occur. The present study shows that this constraint is
      not necessary if the local spatial relationships between the old moving items
      remain constant. It is proposed that, with a fixed configuration, the old moving
      items can be grouped to form a single object. An inhibitory template set up to
      represent the object then coordinates the application of inhibition to the
      individual stimuli. Implications for the theory and ecological flexibility of
      visual marking are discussed.

PMID- 11304019
TI  - Automatic attraction of attention to former targets in visual displays of
      letters.
AB  - Shiffrin and Schneider (1977, Experiment 4d) reported that after consistent
      training in search for particular alphanumeric characters, presentation of one of
      these characters (former targets) as a distractor impeded detection of
      simultaneously presented current targets. Even if presented in an irrelevant
      display location, the former target appeared to attract attention. Here, we
      analyze weaknesses in the design of Experiment 4d and report four follow-up
      experiments ranging from a fairly close replication of the original multiframe
      experiment to a rather conventional single-frame search study. In each
      experiment, presentation of former targets consistently impeded detection of
      simultaneously presented current targets. The results suggest that automatic
      attention attraction to individual alphanumeric characters develops not only in
      the special experimental paradigm used by Shiffrin and Schneider, but also in
      standard visual search tasks. The fact that attention appeared to be attracted by
      shapes as complex as individual letters supports the assumption that
      simultaneously presented visual stimuli can be compared in parallel against
      memory representations of alphanumeric characters.

PMID- 11304020
TI  - The Ponzo illusion and the perception of orientation.
AB  - A new theory, called the tilt constancy theory, claims that the Ponzo illusion is
      caused by the misperception of orientation induced by local visual cues. The
      theory relates the Ponzo illusion-along with the Zollner, Poggendorff, Wundt
      Hering, and cafe wall illusions-to the mechanisms that enable us to perceive
      stable orientations despite changes in retinal orientation or body orientation.
      In Experiment 1, the magnitude of the misperception of orientation was compared
      with the magnitude of the Ponzo illusion. In Experiment 2, predictions of the
      tilt constancy theory were compared with accounts based on (1) low spatial
      frequencies in the image, (2) memory comparisons (pool-and-store model), and (3)
      relative sizejudgments. In Experiment 3, predictions of the tilt constancy theory
      were tested against predictions of the assimilation theory of Pressey and his
      colleagues. In the final experiment, the orientation account was compared with
      theories based on linear perspective and inappropriate size constancy. The
      results support the tilt constancy theory.

PMID- 11304021
TI  - Opioids.

PMID- 11304022
TI  - Visual contrast processing in migraine.
AB  - Some migraine sufferers report certain visual patterns can reliably trigger a
      migraine attack, such as high contrast striped patterns or flickering lights.
      Differences between people with and without migraine on tasks that involve these
      patterns have been attributed to abnormal cortical processing in migraine,
      although the locus and extent of the abnormality remains unclear, as is any
      relationship between impairment on various visual tasks. In this study 58
      migraine sufferers and 61 control subjects participated in three visual tasks
      involving striped patterns. One assessed pattern sensitivity with high contrast
      patterns, the second detection thresholds for low contrast patterns and the third
      supra-threshold contrast scaling. With each measure, the performance of migraine
      sufferers as a group differed to the performance of non-migraine control
      subjects. There were no significant differences between the migraine subgroups
      when classified according to the presence or absence of aura. Cross-correlating
      the results from the three tasks, however, revealed consistent associations:
      impaired or extreme responses on one task were associated with impaired or
      extreme responses on the others. There were no overall effects due to migraine
      duration, the frequency of migraine attacks or the time since the last attack.
      These results are discussed in the context of visually induced migraine, proposed
      causes of abnormal cortical function in migraine and the prospects for developing
      clinically useful tests of visual function.

PMID- 11304023
TI  - Slow cortical potentials in migraine families.
AB  - Amplitude and habituation of event-related potentials are abnormal in migraine.
      We investigated 43 migraine and 41 healthy families to evaluate the influences of
      age, sex and familial contribution on the variance of amplitude and habituation
      of the contingent negative variation (CNV). Analysis of individual differences in
      relation to the CNV habituation was performed. The study demonstrated that
      habituation of the early CNV component characterizes migraine considerably better
      than the CNV amplitudes. Habituation, however, is strongly influenced by age.
      Migraine adults and children generally showed reduced habituation. Surprisingly,
      more than 30% of the healthy adults demonstrated a marked loss of habituation.
      The reduced CNV habituation represented a high sensitivity but low specificity to
      migraine, especially in children. CNV amplitude and habituation parameters
      revealed a considerable familial contribution associated with migraine. No
      familial influence on either morphology or habituation of the CNV in healthy
      families or between healthy members of migraine families was observed. The low
      specificity and familial transmission of CNV parameters in members of migraine
      families suggest that increased amplitudes and reduced habituation of CNV do not
      constitute a primary risk factor for migraine, but rather represent a
      predisposition. Genetic components probably affect variation of the CNV amplitude
      and habituation.

PMID- 11304024
TI  - The prevalence of migraine in women aged 40-74 years: a population-based study.
AB  - The objective of this study was to investigate the age-dependence of the
      prevalence and characteristics of migraine headache and migraine visual aura. A
      neurologist interviewed 728 women attending a mammography screening programme.
      International Headache Society (IHS) criteria were used. The lifetime prevalence
      of migraine headache was 31.5% and the 1-year prevalence 18.0%. The magnitude of
      the decline of the prevalence of active (one or more attacks in the previous
      year) migraine headache was estimated to 50% per decade. The prevalence of active
      migraine visual aura was 3.8%. This did not vary by age. Except for the pain
      intensity and the presence of nausea, other characteristics and concomitant
      symptoms did not change with age. Active migraine headache and migraine visual
      aura in middle-aged and older women are common and modified differently by age.
      We suggest that the decline of prevalence of active migraine headache with age is
      caused by a decrease in pain intensity.

PMID- 11304025
TI  - Prevalence of migraine and non-migrainous headache--head-HUNT, a large population
      based study.
AB  - The objective of this study was to estimate the 1-year prevalence of the
      following categories of headache; migraine, non-migrainous headache, frequent
      headache (>6 days/month), and chronic headache (>14 days/month). Between 1995 and
      1997, all 92,566 inhabitants 20 years and older in Nord-Trondelag county in
      Norway were invited to a comprehensive health study. Out of 64,560 participants,
      a total of 51,383 subjects (80%) completed a headache questionnaire. The overall
      age-adjusted 1-year prevalence of headache was 38% (46% in women and 30% in men).
      The prevalence of migraine was 12% (16% in women and 8% in men), and for non
      migrainous headache 26% (30% in women and 22% in men). For frequent headache (> 6
      days per month) and for chronic headache (>14 days per month), the prevalence was
      8% and 2%, respectively. Women had a higher prevalence than men in all age groups
      and for all headache categories. Prevalence peaked in the fourth decade of life
      for both men and women, except for 'frequent non-migrainous headache', which was
      nearly constant across all age groups in both genders. In accordance with
      findings in other western countries, we found that headache suffering, including
      migraine, was highly prevalent, especially in younger women.

PMID- 11304026
TI  - Nitric oxide metabolites, prostaglandins and trigeminal vasoactive peptides in
      internal jugular vein blood during spontaneous migraine attacks.
AB  - Despite evidence emerging from the experimental model of nitroglycerin-induced
      headache, the endogenous increase in nitric oxide (NO) production during migraine
      attacks is only speculative. It has been hypothesized that there is a close
      relationship between activation of the L-arginine/NO pathway and production of
      certain vasoactive and algogenic prostaglandins during spontaneous migraine
      attacks, but this suggestion also needs to be confirmed. In the present study the
      levels of nitrites, the stable metabolites of NO, were determined with high
      performance liquid chromatography (HPLC) in the internal jugular venous blood of
      five patients affected by migraine without aura examined ictally. These samples
      were taken within 30 min, 1, 2, and 4 h from the onset of the attack and at the
      end of the ictal period. At the same time, the plasma levels of calcitonin gene
      related peptide (CGRP), neurokinin A (NKA), prostaglandin E2 (PGE2) and 6 keto
      PGF1alpha, the stable product of PGI2, were assessed with radioimmunoassay (RIA)
      kits in the same samples. The levels of the intracellular messengers, cGMP and
      cAMP, were also measured with the RIA method. Nitrite, cGMP, CGRP and NKA levels
      reached their highest values at the first hour, then they tended to decrease
      progressively and returned, after the end of attacks, to values similar or below
      those detected at the time of catheter insertion (ANOVA, statistical
      significance: P<0.001; P<<0.002; P<0.002; P<0.003, respectively). PGE2 and 6 keto
      PGF1alpha, as well as cAMP levels also significantly increased at the first hour
      but reached a peak at the 2nd hour and remained in the same range until the 4th
      and 6th hours. Then their values tended to decrease after the end of attacks,
      becoming lower than those measured immediately after catheter positioning for
      internal jugular venous blood drawing (ANOVA: P<0.002, P<0.004, P<0.001,
      respectively). Our results support early activation of the L-arginine/NO pathway
      which accompanies the release of vasoactive peptides from trigeminal endings and
      a late rise in the synthesis of prostanoids with algogenic and vasoactive
      properties which may intervene in maintaining the headache phase.

PMID- 11304027
TI  - Possible mechanisms of glyceryl-trinitrate-induced immediate headache in patients
      with chronic tension-type headache.
AB  - Nitric oxide (NO) plays an important role in the pathophysiology of primary
      headaches including chronic tension-type headache (CTTH). Thus, a NO synthase
      inhibitor reduces headache and muscle hardness while the NO donor glyceryl
      trinitrate (GTN) causes more headache in patients than in healthy controls.
      Sensitization of myofascial pain pathways is important in CTTH, and the aim of
      the present study was to investigate if such mechanisms may also explain GTN
      induced immediate headache in patients with CTTH. In a randomized, double-blind,
      crossover study 16 patients with CTTH and 16 healthy subjects received
      intravenous infusion of GTN (0.5 microg/kg per min for 20 min) or placebo on two
      headache-free days separated by at least 1 week. Muscle hardness, myofascial
      tenderness, mechanical and heat pain thresholds were measured at baseline and at
      60 min and 120 min after start of infusion. In patients, GTN infusion resulted in
      a biphasic response with immediate headache and more pronounced delayed headache.
      A similar but less pronounced response was seen in controls. There was no
      difference between GTN and placebo regarding muscle hardness, myofascial
      tenderness or pressure and heat pain thresholds in either patients or controls
      (P>0.05). The unchanged sensitivity of pericranial myofascial pain pathways
      indicates that peripheral and central sensitization is not involved in the
      mechanisms of GTN-induced immediate headache.

PMID- 11304028
TI  - A prospective study of migraine with aura attacks in a headache clinic
      population.
AB  - In order to investigate the prevalence of migraine with aura (MA) attacks
      according to the criteria set by the International Headache Society (IHS) for
      diagnosis down to the three-digit level of classification, and to determine the
      recurrence and possible variability of MA attacks over time, we conducted a 6-15
      month-long prospective study on 64 MA patients (42 women and 22 men)
      consecutively referred for the first time to the University of Parma Headache
      Centre. At the end of the follow-up period, diagnosis was the same as at the
      first visit for 80.0% of patients, while it was changed for 20.0%. Throughout the
      duration of the study, the average number of attacks for each patient was 5.3 +/-
      6.2 (range 0-30). Attacks of migraine with typical aura were the most frequent
      (69.1% of patients), but migraine aura without headache (29.1%) and migraine with
      prolonged aura (20.0%) were also common; by contrast, basilar migraine and
      migraine with acute onset aura were reported only by one patient in either case.
      Migraine aura without headache was statistically significantly more frequent in
      males than in females. Our study results suggest that in most cases the frequency
      of recurrent MA attacks is relatively low and provide interesting indications
      about the prevalence of the different MA subtypes listed in the IHS
      classification, albeit in a headache clinic population.

PMID- 11304029
TI  - Radiotherapy in a case of Tolosa-Hunt syndrome.

PMID- 11304030
TI  - A quantitative risk assessment for fumonisins B1 and B2 in US corn.
AB  - Quantitative risk analysis permits modifying risk estimates with changes in
      variables such as exposure. This analysis for exposure to the mycotoxin fumonism
      describes the magnitude of adverse effects, variability in the population and
      uncertainty of models as a range of possible outcomes. The most sensitive adverse
      response in rats, nephrotoxic lesions, was used for the dose-response analysis.
      Dietary intake of corn products was estimated from a 3-day consumption survey.
      Levels of corn in each product were estimated by standard methods. Fumonisin
      levels in corn products were estimated from Food and Drug Administration (FDA)
      surveillance data and distributions of fumonisin consumption were modelled for
      each eater in the survey population. Uncertainty for predictions made from each
      model and uncertainty resulting from model selection were described. Results of
      the dose-response and exposure analyses were assimilated in a two-dimensional
      Monte-Carlo simulation. Distributions representing variability and uncertainty
      were iteratively selected to form an array of estimates of the risk. On the basis
      of this analysis, current dietary levels of fumonisin would not result in renal
      lesions even at upper levels of exposure. To avoid toxicity at much higher doses,
      limiting corn intake would be more effective than would limiting the level of
      fumonisin in corn.

PMID- 11304031
TI  - Preliminary evaluation of fumonisins by the Nordic countries and occurrence of
      fumonisins (FB1 and FB2) in corn-based foods on the Danish market.
AB  - Experts from the Nordic countries (Denmark, Norway, Sweden, Finland and Iceland)
      have carried out an evaluation of fumonisins. The working group members concluded
      that, at that time point, it was not possible to carry out a complete risk
      assessment. However, it was recommended that the human daily' intake of
      fumonisins should be less than 1 microg/kg bw/day. Subsequently, the presence of
      the Fusarium mycotoxins fumonisin B1 and B2 (FB1 and FB2) in corn-based food on
      the Danish retail market has been determined. A total of 70 samples were analysed
      and 37% contained FB1 and 21% contained FB2. No fumonisins were found in sweet
      corn (canned or frozen), corn-on-the-cob, corn starch or gruel powder for babies.
      FB1 was found in about half of the corn flakes, corn snack and popcorn (not
      popped) samples, whereas FB2 was seen to a lesser extent. Both FB1 and FB2 were
      found in 75% or more of the corn flour, tacos and polenta samples. In general,
      the content of FB1 was in the range of 1-1000 micro/kg and the content of FB2 was
      in the range of 4-250 microg/kg. Corn-based foods are consumed in rather low
      amounts and irregularly among the Danish population and therefore it is not
      meaningful to calculate an average daily funonisin intake. An estimate for an
      'eater' shows that the intake of fumonisins will not exceed 0.4 microg/kg bw/day.

PMID- 11304032
TI  - Determination of fumonisins B1 and B2 in cornflakes by high performance liquid
      chromatography and immunoaffinity clean-up.
AB  - The determination of fumonisins in cornflakes is a challenging matter as the
      actually available methods for the analysis of corn do not perform well when
      applied to this more complex matrix. After testing several factors that may
      affect the analytical performance, an accurate method for the determination of
      fumonisin B1 (FB1) and B2 (FB2) in cornflakes has been developed. The method uses
      immunoaffinity chromatography for clean-up and high performance liquid
      chromatography (HPLC) for quantification of the toxins. Samples were extracted
      twice with acetonitrile-methanol-water (25:25:50) and the combined extracts were
      diluted with phosphate buffered saline (PBS) and applied to a FumoniTest
      immunoaffinity column. After washing with PBS, fumonisins were eluted from the
      column with methanol and reacted with o-phthaldialdehyde/2-mercaptoethanol to
      form fluorescent derivatives. Fumonisin derivatives were analysed by reversed
      phase HPLC with fluorometric detection using methanol-0.1 M phosphate buffer
      (77:23; pH adjusted at 3.35) as mobile phase. The average recoveries for FB1 and
      FB2 spiked in the ranges of 0.33 2.80 microg/g and 0.17-1.40 microg/g were 102.6%
      and 95.1%, respectively, with average relative standard deviations of 9% and 8%.
      The limit of quantification for FB1 and FB2 was 0.005 microg/g based on a signal
      to-noise ratio of 6.1 by using a sensitive fluorescence detector. The method was
      used to analyse 18 cornflakes and cornflake cereals samples/for FB1 and FB2
      contamination. All but one sample were found to be contaminated, with maximum FB1
      and FB2 concentrations of 1.092 microg/g and 0.235 microg/g, respectively. Mean
      FB1 and FB2 concentrations were 0.157 microg/(g and 0.036 microg/g, respectively.

PMID- 11304033
TI  - A mechanistic approach to modelling the risk of liver tumours in mice exposed to
      fumonisin B1 in the diet.
AB  - Data from the National Toxicology Program's carcinogenesis study of fumonisin B1
      in B6C3F1 mice, conducted at the National Center for Toxicological Research, were
      used to fit the Moolgavkar-Venzon-Knudson (MVK) two-stage, clonal-expansion model
      of carcinogenesis. In addition to tumour data from the conventional 2-year
      bioassay, the study included data on tissue weights, cell proliferation, cell
      death, and sphingolipid metabolism in primary target organs. The model was used
      to predict 2-year liver tumour rates in female and male mice based on differences
      among dose groups in the effect of fumonisin B1 on the growth of normal tissue
      and on the proliferation of preneoplastic cells as a compensatory response to
      sphinganine-induced cell death. Fumonisin B1 was assumed to be non-genotoxic,
      i.e. the model did not include any effect of fumonisin B1 on either of the two
      mutation rates of the MVK model. The model was able to reproduce reasonably well
      the observed tumour rates in both female and male mice, predicting substantially
      increased rates above background only at the highest doses of fumonisin B1 in
      females.

PMID- 11304034
TI  - Tissue sphinganine as a biomarker of fumonisin-induced apoptosis.
AB  - NCTR measured sphinganine concentrations in the livers of mice and in the livers
      and kidneys of rats in conjunction with a tumour bioassay. In our model of the
      tumour incidence, target-tissue levels of sphinganine serve as a biomarker for a
      dose response of fumonisin B1 on cell death. Initially we questioned the utility
      of sphinganine levels in this role because they were highly variable when
      compared across time points. In spite of this concern, a conceptual framework and
      data are presented that support the use of sphinganine as a biomarker for a dose
      response of fumonisin B1 on cell death. This framework is reasonably consistent
      with observed sphinganine concentrations in the examined tissues, the literature
      on fumonisin's effects on sphingolipid synthesis, and our hypothesized mechanism
      through which fumonisin B1 increases age-specific tumour incidence.

PMID- 11304035
TI  - Determination of sphinganine, sphingosine and Sa/So ratio in urine of humans
      exposed to dietary fumonisin B1.
AB  - Fumonisin B1 (FB1) is an inhibitor of sphinganine N-acyltransferase and the
      increase in the sphinganine/ sphingosine (Sa/So) ratio in urine or serum has been
      proposed as a biomarker to evaluate exposure to fumonisins. The objectives of
      this study were to (1) develop a liquid chromatographic method sufficiently
      sensitive to determine the low concentration of free Sa in male human urine, and
      (2) analyse So and Sa in human urine and monitor the Sa/So ratio in urine of
      humans exposed to FB1 in corn diets over 1 month. The liquid chromatographic
      method involved isolation from human urine of exfoliated cells followed by an
      extraction of free sphingoid bases and their separation and quantification by
      high performance liquid chromatography. The detection limits for So and Sa were
      0.15 ng/ml in female urine (2 ml used) and 0.005 ng/ ml in male urine (60 ml
      used). Twenty-eight healthy adult volunteers consumed for 1 month a normal diet
      containing their homegrown corn potentially contaminated with FB1. Immediately
      preceding the start of the test, morning urine samples for the determination of
      So and Sa were collected from each person, and the corn samples used in cooking
      were obtained from each family for the determination of FB1. At the end of the
      test period, morning-urine samples were collected from each person and analysed
      again. The daily FB1 intakes were estimated and used to assess the relationship
      between them and the urinary Sa/So ratios in humans exposed to dietary FB1 over 1
      month. All the homegrown corn samples contained FB1 ranging from 0.08 to 41.1
      mg/kg, and the estimated daily FB1 intakes ranged from 0.4 to 740 microg/kg
      b.w./day. The 1-month monitoring results suggest that sphingolipid metabolism of
      humans could be affected by FB1 intake, the urinary Sa/So ratio may be useful for
      evaluating FB1 exposure when the contamination of FB1 is high, and that males are
      more sensitive to FB1 disruption of sphingolipid metabolism than females.

PMID- 11304036
TI  - What does the study of the spatial patterns of pathological lesions tell us about
      the pathogenesis of neurodegenerative disorders?
AB  - Discrete pathological lesions, which include extracellular protein deposits,
      intracellular inclusions and changes in cell morphology, occur in the brain in
      the majority of neurodegenerative disorders. These lesions are not randomly
      distributed in the brain but exhibit a spatial pattern, that is, a departure from
      randomness towards regularity or clustering. The spatial pattern of a lesion may
      reflect pathological processes affecting particular neuroanatomical structures
      and, therefore, studies of spatial pattern may help to elucidate the pathogenesis
      of a lesion and of the disorders themselves. The present article reviews first,
      the statistical methods used to detect spatial patterns and second, the types of
      spatial patterns exhibited by pathological lesions in a variety of disorders
      which include Alzheimer's disease, Down syndrome, dementia with Lewy bodies,
      Creutzfeldt-Jakob disease, Pick's disease and corticobasal degeneration. These
      studies suggest that despite the morphological and molecular diversity of brain
      lesions, they often exhibit a common type of spatial pattern (i.e. aggregation
      into clusters that are regularly distributed in the tissue). The pathogenic
      implications of spatial pattern analysis are discussed with reference to the
      individual disorders and to studies of neurodegeneration as a whole.

PMID- 11304037
TI  - Lectin cytochemistry of rat cerebral and cerebellar neuronal cells.
AB  - Lectin cytochemistry of normal rat central nervous system (CNS) was performed on
      formalin-fixed, paraffin-embedded sections by using 14 lectins and light and
      electron microscopy. Hippocampal neurons reacted positively with Griffonia
      (Bandeiraea) simplicifolia lectin I (GSL-I), Griffonia (Bandeiraea) simplicifolia
      lectin II (GSL-II) and Vicia villosa agglutinin (VVA); neurons in the cornu
      ammonis (CA) 2 region reacted positively with GSL-I and GSL-II, and neurons in
      the CA2 and CA3 regions reacted with VVA. Cortical neurons reacted positively
      with GSL-I and VVA. Cerebellar Purkinje cells and granule cells were reactive
      with Phaseolus vulgaris leukoagglutinin (PHA-L). Cerebellar nucleus neurons were
      also reactive with PHA-L and VVA. Reactivity with GSL-I, GSL-II, VVA and PHA-L
      was observed only on the neuronal cell surface. The present findings demonstrate
      the differences between cerebral and cerebellar neurons in reacting with
      glycoconjugates.

PMID- 11304038
TI  - Spatial pattern of prion protein deposits in patients with sporadic Creutzfeldt
      Jakob disease.
AB  - The spatial pattern of the prion protein (PrP) deposits was studied in the
      cerebral cortex and cerebellum in 10 patients with sporadic Creutzfeldt-Jakob
      disease (CJD). In all patients the PrP deposits were aggregated into clusters
      and, in 90% of cortical areas and in 50% of cerebellar sections, the clusters
      exhibited a regular periodicity parallel to the tissue boundary; a spatial
      pattern also exhibited by beta-amyloid (Abeta) deposits in Alzheimer's disease
      (AD). In the cerebral cortex, the incidence of regular clustering of the PrP
      deposits was similar in the upper and lower cortical laminae. The sizes of the
      PrP clusters in the upper and lower cortex were uncorrelated. No significant
      differences in mean cluster size of the PrP deposits were observed between brain
      regions. The size, location and distribution of the PrP deposit clusters suggest
      that PrP deposition occurs in relation to specific anatomical pathways and
      supports the hypothesis that prion pathology spreads through the brain via such
      pathways. In addition, the data suggest that there are similarities in the
      pathogenesis of extracellular protein deposits in prion disease and in AD.

PMID- 11304039
TI  - Acute focal demyelinating disease simulating brain tumors: histopathologic
      guidelines for an accurate diagnosis.
AB  - The object of the present study was to determine the histopathological guidelines
      for accurate diagnosis of cases of acute focal demyelinating disease that
      simulates brain tumors. The surgical pathology of three such cases is assessed.
      Histopathological keys to the diagnosis of such cases are as follows. First, a
      pattern of sheets of atypical gemistocytic astrocytes in the white matter that
      show well-formed processes and that are adequately distanced from each other
      argues against a diagnosis of neoplasm. Second, uniform distribution of foamy
      macrophages aligned along axons, with occasional focal collections surrounding
      blood vessels and in the absence of any associated coagulative necrosis argues
      against the presence of a tumor. Third, perivascular chronic inflammatory
      infiltration, especially a mixture of lymphocytes and macrophages, favors the
      diagnosis of demyelination plaque. In such cases the lymphocytes will be
      predominantly T cells. Fourth, pleomorphic astrocytic proliferation with a lack
      of vascular endothelial proliferation should raise the suspicion that the lesion
      may not be a brain tumor. These diagnostic keys should be followed when
      diagnosing cases that are suspected to be demyelination processes rather than
      brain tumors. The presence of demyelination plaque should then be confirmed by
      imaging modalities such as staining with myelin-and axon-specific stains.

PMID- 11304040
TI  - Neurodegenerative features in developmental brain disorders.
AB  - The authors examined the occurrence of neurofibrillary tangles (NFT), senile
      plaques, spheroids in Goll's nucleus, grumose or foamy spheroid bodies (GFSB) in
      the basal ganglia, and hyaline inclusions in the brainstem nuclei in 62 patients
      under 40 years of age with non-progressive developmental brain disorders. Five
      cases had demonstrated NFT, which tended to be confined to the subcortical
      nuclei, whereas no senile plaques were identified in any case. Spheroids in
      Goll's nucleus were significantly increased in three cases of congenital brain
      anomalies and five cases of perinatal hypoxic ischemic encephalopathy. The GFSB
      positive subjects were clinicopathologically divided into two subgroups
      consisting of four cases of congenital malformations, which were also associated
      with severe respiratory failure, and six cases of perinatal brain disorders in
      which the basal ganglia were severely affected. Eosinophilic intracytoplasmic
      inclusions, unlike the hyaline inclusions of the Lewy type, were found in the
      substantia nigra and/or locus ceruleus in two subjects. It is speculated that a
      variety of mechanisms, including accelerated aging and anoxic insults, may be
      involved in the increased occurrence of NFT and/or spheroids in non-progressive
      developmental disorders. A detailed investigation is useful to clarify the
      neuronal changes secondary to the brain damages early in development.

PMID- 11304041
TI  - Alternative EWS-FLI1 fusion gene and MIC2 expression in peripheral and central
      primitive neuroectodermal tumors.
AB  - Primitive neuroectodermal tumors (PNET) occur either in the central nervous
      system (CNS; central PNET, cPNET) or in the peripheral sites (peripheral PNET,
      pPNET). Recent molecular approaches have been defining a new concept of PNET,
      that is, the pPNET including Ewing's sarcoma (ES) which expresses MIC2
      glycoprotein and shows the specific chimeric gene of EWS-FLI1. The expression of
      MIC2 and the genetic rearrangement of EWS-FLI1 are considered to be highly
      specific to the pPNET/ES. This study examined the expression of MIC2 and EWS-FLI1
      gene by means of immunohistochemistry and reverse transcriptase-polymerase chain
      reaction (RT-PCR) on various small round cell tumors originating in the CNS or
      non-CNS organs. All peripheral PNET tested expressed MIC2 and were positive for
      EWS-FLI1 (11/11). In contrast, all cPNET and other blastic CNS tumors were
      negative for MIC2: medulloblastoma (0/3), cerebral PNET (0/2), spinal PNET (0/2),
      glioblastoma (0/2), retinoblastoma (0/3), and pineoblastoma (0/2). These MIC2
      negative tumors were also negative for the chimeric gene product of EWS-FLI1.
      Interestingly, one PNET originating in the intracranial dura mater was positive
      for both MIC2 and EWS-FLI1 fusion gene. The results indicate that cPNET lacks any
      genetic or protein markers, except for a meningeal PNET which falls into the same
      phenotypic spectrum of pPNET.

PMID- 11304042
TI  - Unusual triplet expansion associated with neurogenic changes in a family with
      oculopharyngeal muscular dystrophy.
AB  - The occasional observation of neurogenic features in oculopharyngeal muscular
      dystrophy (OPMD) is unclear both in nosological and in etiological respects.
      Studies are reported here of a family with autosomal-dominant OPMD involving
      seven members over three generations. In three of them muscle biopsies were
      performed. Two of the patients (a 45-year-old sister and a 57-year-old brother of
      the third generation) were studied in more detail and, in addition to the typical
      changes of OPMD, showed a neurogenic component both by electrophysiology and
      morphology. Molecular genetic investigations revealed a repeat unit of
      (GCG/GCA)13 in the first exon of the poly(A)binding-protein2 gene in both
      siblings. A possible association of this unusually long triplet repeat extension
      with the atypical phenotype is considered and has to be verified in other cases.

PMID- 11304043
TI  - An autopsy case of the schizophrenic 32 years after lobotomy.
AB  - An autopsy case is reported here of a 69-year-old patient with schizophrenia, who
      was known retrospectively to have had a prefrontal lobotomy 32 years previously.
      The patient was diagnosed as schizophrenic at the age of 24 and the lobotomy was
      undertaken 13 years later. The patient was recently found outside in a dehydrated
      condition and admitted to a general hospital, where he died of respiratory
      failure. Bilateral cystic lesions were found in the deep white matter of the
      frontal lobe. The cyst walls consisted of glial fibrous tissues, and severe
      demyelination with axonal destruction was diffusely observed in the white matter
      of the frontal lobe. In the thinner frontal cortex without arcuate fibers (U
      fibers) close to the cavities, cytoarchitectural abnormalities were observed. In
      the thalamic nuclei marked retrograde degeneration and astrocytic gliosis were
      observed. The detailed neuropathological findings of a lobotomized schizophrenic
      brain are reported here. It is proposed that one should be reminded of a
      lobotomized brain if bilateral cysts are found.

PMID- 11304044
TI  - Japanese familial amyotrophic lateral sclerosis family with a two-base deletion
      in the superoxide dismutase-1 gene.
AB  - The clinical characteristics of members of a familial amyotrophic lateral
      sclerosis (FALS) family from Oki Island, whose members have a 2-bp deletion at
      codon 126 of Cu/Zn superoxide dismutase (SOD1) gene, are presented here. Mean age
      of the onset in the members was 42 years. Mean disease duration among the members
      who had not been placed on a respirator was approximately 2 years. Long-term
      survivors with respiratory support presented disturbances in eye movement and
      urination toward the end stages of the disease. They predominantly exhibited
      lower motor neuron symptoms. In addition, the authors focused on frameshift,
      nonsense and non-amino-acid-altering mutations. Frameshift and nonsense mutations
      were all found within exon 4, exon 5 and intron 4. These amyotrophic lateral
      sclerosis cases were likely to have shorter disease duration than the FALS
      patients with single substitution. Several hypotheses were presented on the
      pathogenesis of FALS with SOD1 mutation.

PMID- 11304046
TI  - Transgenic mouse model for familial amyotrophic lateral sclerosis with superoxide
      dismutase-1 mutation.
AB  - Familial amyotrophic lateral sclerosis (ALS) with mutations in the gene for
      superoxide dismutase-1 (SOD1) is clinicopathologically reproduced by transgenic
      mice expressing mutant forms of SOD1 detectable in familial ALS patients. Motor
      neuron degeneration associated with SOD1 mutation has been thought to result from
      a novel neurotoxicity of mutant SOD1, but not from a reduction in activity of
      this enzyme, based on autosomal dominant transmission of SOD1 mutant familial ALS
      and its transgenic mouse model, clinical severity of the ALS patients independent
      to enzyme activity, no ALS-like disease in SOD1 knockout or wild-type SOD1
      overexpressing mice, and clinicopathological severity of mutant SOD1 transgenic
      mice dependent on transgene copy numbers. Proposed mechanisms of motor neuron
      degeneration such as oxidative injury, peroxynitrite toxicity, cytoskeletal
      disorganization, glutamate excitotoxicity, disrupted calcium homeostasis, SOD1
      aggregation, carbonyl stress and apoptosis have been discussed. Intracytoplasmic
      vacuoles, indicative of increased oxidative damage to the mitochondria and
      endoplasmic reticulum, in the neuropil and motor neurons appear in high
      expressors of mutant SOD1 transgenic mice but not in low expressors of the mice
      or familial ALS patients, suggesting that overexpression of mutant SOD1 in mice
      may enhance oxidative stress generation from this enzyme. Thus, transgenic mice
      carrying small transgene copy numbers of mutant SOD1 would provide a beneficial
      animal model for SOD1 mutant familial ALS. Such a model would contribute to
      elucidating the pathomechanism of this disease and establishing new therapeutic
      agents.

PMID- 11304045
TI  - Formation of advanced glycation end-product-modified superoxide dismutase-1
      (SOD1) is one of the mechanisms responsible for inclusions common to familial
      amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic
      mice expressing human SOD1 gene mutation.
AB  - Neuronal Lewy body-like hyaline inclusions (LBHI) and astrocytic hyaline
      inclusions (Ast-HI) are morphological hallmarks of certain familial amyotrophic
      lateral sclerosis (FALS) patients with superoxide dismutase-1 (SOD1) gene
      mutations, and transgenic mice expressing the human SOD1 gene mutation. The
      ultrastructure of inclusions in both diseases is identical: the essential common
      constituents are granule-coated fibrils approximately 15-25nm in diameter and
      granular materials. Detailed immunohistochemical analyses have shown that the
      essential common protein of the inclusions in both diseases is an SOD1 protein.
      This finding, together with the immunoelectron microscopy finding that the
      abnormal granule-coated fibrils comprising the inclusions are positive for SOD1,
      indicates that these granule-coated fibrils containing SOD1 are important
      evidence for mutant SOD1-linked disease in human and mouse. For immunoelectron
      microscopy, the granule-coated fibrils are modified by advanced glycation
      endproducts (AGE) such as N(epsilon)-carboxymethyl lysine, pyrraline and
      pentosidine (Maillard reaction). Based on the fact that AGE themselves are
      insoluble molecules with direct cytotoxic effects, the granule-coated fibrils and
      granular materials are not digested by the lysosomal and ubiquitin systems. The
      neurons and astrocytes of the normal individuals and non-transgenic mice show no
      significant immunoreactivity for AGE. Considered with the mutant-SOD1 aggregation
      toxicity, a portion of the SOD1 comprising both types of the inclusion is
      modified by the AGE, and the formation of the AGE-modified SOD1 (probably AGE
      modified mutant SOD1) is one of the mechanisms responsible for the aggregation
      (i.e. granule-coated fibril formation).

PMID- 11304047
TI  - Cerebral arteries from a 54-year-old man with recurrent cerebral bleeding.

PMID- 11304048
TI  - Muscle biopsy of a 15-year-old boy with muscle atrophy and weakness of the
      extremities from infancy.

PMID- 11304049
TI  - Meningeal mass in a 40-year-old woman with slight headache.

PMID- 11304050
TI  - Hypothalamic mass in a 28-year-old man with diabetes insipidus ataxia, nystagmus
      and dysarthria.

PMID- 11304051
TI  - The influence of zinc supplementation on morbidity due to Plasmodium falciparum:
      a randomized trial in preschool children in Papua New Guinea.
AB  - Zinc is crucial for normal immune function and can reduce morbidity from multiple
      infectious diseases. To determine the influence of zinc on malaria morbidity we
      conducted a randomized placebo-controlled trial of daily zinc supplementation in
      children residing in a malaria endemic region of Papua New Guinea. A total of 274
      preschool children aged 6 to 60 months were given 10 mg elemental zinc (n = 136)
      or placebo (n = 138) for 6 days a week for 46 weeks. Slide-confirmed malaria
      episodes were detected by surveillance of cases self-reporting to a local health
      center. Cross-sectional surveys were conducted at the beginning, middle, and end
      of the study to assess infection rates, parasite density, spleen enlargement, and
      hemoglobin levels. Zinc supplementation resulted in a 38% (95% CI 3-60, P =
      0.037) reduction in Plasmodium falciparum health center-based episodes, defined
      as parasitemia > or = 9200 parasites/microl with axial temperature > or = 37.5
      degreesC or reported fever. Episodes accompanied by any parasitemia were also
      reduced by 38% (95% CI 5-60, P = 0.028), and episodes with parasitemia > or =
      100,000/microl were reduced by 69% (95% CI 25-87, P = 0.009). There was no
      evidence of the effects of zinc on Plasmodium vivax morbidity or on health center
      attendance for causes other than P. falciparum. Zinc had no consistent effect on
      cross-sectional malariometric indices. Although P. falciparum prevalence tended
      to be lower at the end of the study in children given the placebo, such changes
      were absent at the mid-study survey. These results suggest that improved dietary
      zinc intake may reduce morbidity due to P. falciparum.

PMID- 11304052
TI  - Severe anemia in young children after high and low malaria transmission seasons
      in the Kassena-Nankana district of northern Ghana.
AB  - Malaria and anemia accounted for 41% and 18% respectively of hospital deaths in
      the Kassena-Nankana district of northern Ghana during 1996. We measured
      hemoglobin (Hb), malaria prevalence, and anthropometric indices of 6--24-month
      old infants and young children randomly selected from this community at the end
      of the high (May-October, n = 347) and low (November-April, n = 286) malaria
      transmission seasons. High transmission season is characterized by rainfall (the
      equivalent of 800-900 mm/yr.), while the remaining months receive less than 50
      mm/yr. Severe anemia, defined as Hb < 6.0 g/dL, was 22.1% at the end of the high
      transmission season compared to 1.4% at the end of the low transmission season
      (Odds Ratio [OR] = 20.1; 95% CI: 7.1-55.3). Parasitemia was 71% and 54.3% at
      these time points (OR = 2.1; 95% CI: 1.5-2.9). Nutritional anemia appeared to
      have little impact upon this seasonal difference since anthropometric indices
      were comparable. Although the relative contributions of other causes of severe
      anemia were not assessed, repeated malaria infections may be a primary
      determinant of severe anemia among infants and young children during the high
      transmission season.

PMID- 11304053
TI  - Repeated infection of Aotus monkeys with Plasmodium falciparum induces protection
      against subsequent challenge with homologous and heterologous strains of
      parasite.
AB  - We evaluated repeated blood-stage infections with Plasmodium falciparum in eight
      Aotus lemurinus lemurinus monkeys. Over the course of seven infections with 10(4)
      P. falciparum (the Vietnam Oak Knoll [FVO] strain), the pre-patent period
      lengthened from 8.2 to 30.8 days; the peak parasitemia decreased from 4.5 x 10(5)
      to 0 parasites/microl (Challenges 6 and 7), and the requirement for treatment
      decreased from 100% to 0% (Challenges 3 to 7). Five weeks after the seventh FVO
      challenge, the eight immune and three naive monkeys received 10(4) parasitized
      erythrocytes infected with P. falciparum (CAMP strain). The three control animals
      experienced uncontrolled parasitemias reaching between 4.8 and 7.7 x 10(5)
      parasites/microl (pre-patency = 6.3 days) and all required drug treatment; six of
      the eight immune monkeys became parasitemic (pre-patency = 8.8 days), but self
      cured. Two of three of the monkeys having the greatest reductions in hematocrit
      (50-60%) also had the highest parasitemias (approximately 10(4) parasites/microl)
      before self-curing. Repeated homologous infections induced sterile immunity to
      homologous challenge; during heterologous challenge the monkeys developed
      clinically relevant, but not life-threatening, parasitemias and anemia.

PMID- 11304054
TI  - Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI
      GSD-218.
AB  - We conducted a phase II, randomized, double-blind, placebo-controlled, safety and
      immunogenicity study of a serially passaged, plaque-purified live chikungunya
      (CHIK) vaccine in 73 healthy adult volunteers. Fifty-nine volunteers were
      immunized one time subcutaneously with the CHIK vaccine and 14 were immunized
      with placebo (tissue culture fluid). Vaccinees were clinically evaluated
      intensively for one month, and had repeated blood draws for serological assays
      (50% plaque-reduction neutralization test) for one year. Except for transient
      arthralgia in five CHIK vaccinees, the number and severity of local and systemic
      reactions and abnormal laboratory tests after immunization were similar in CHIK
      vaccinees and placebo recipients. Fifty-seven (98%) of 58 evaluable CHIK
      vaccinees developed CHIK neutralizing antibody by day 28, and 85% of vaccinees
      remained seropositive at one year after immunization. No placebo recipients
      seroconverted. This promising live vaccine was safe, produced well-tolerated side
      effects, and was highly immunogenic.

PMID- 11304055
TI  - Predictors of chloroquine treatment failure in children and adults with
      falciparum malaria in Kampala, Uganda.
AB  - Chloroquine-resistant falciparum malaria is a serious problem in much of sub
      Saharan Africa. However, it is desirable to continue to use chloroquine as first
      line therapy for uncomplicated malaria where it remains clinically effective. To
      identify predictors of chloroquine treatment failure, a 14-day clinical study of
      chloroquine resistance in patients with uncomplicated falciparum malaria was
      performed in Kampala, Uganda. Among the 258 patients (88% follow-up), 47% were
      clinical failures (early or late treatment failure) and 70% had parasitological
      resistance (RI-RIII). Using multivariate analysis, an age less than five (odds
      ratio [OR] = 3.4, 95% CI = 1.8-6.3) and a presenting temperature over 38.0
      degreesC (OR = 2.0, 95% CI = 1.1-3.7) were independent predictors of treatment
      failure. In addition, patients who last took chloroquine 3 to 14 days prior to
      study entry were significantly more likely to be treatment failures compared to
      patients with very recent (less than 3 days) or no recent chloroquine use. In
      areas with significant chloroquine resistance, easily identifiable predictors of
      chloroquine treatment failure might be used to stratify patients into those for
      whom chloroquine use is acceptable and those for whom alternative treatment
      should be used.

PMID- 11304056
TI  - Assessing drug sensitivity of Plasmodium vivax to halofantrine or choroquine in
      southern, central Vietnam using an extended 28-day in vivo test and polymerase
      chain reaction genotyping.
AB  - Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and
      Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or
      halofantrine in two villages in southern, central Vietnam. This area has
      chloroquine-resistant Plasmodium falciparum but no documented chloroquine
      resistant P. vivax. Standard dose chloroquine (25 mg/kg, over 48 hours) or
      halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients,
      respectively. End points were parasite sensitivity or resistance determined at 28
      days. Of the evaluable patients, 23/23 100% (95% confidence interval [CI] 85.1
      100) chloroquine and 21/24 (87.5%) (95% CI 67.6-97.3) halofantrine-treated
      patients were sensitive. Three halofantrine recipients had initial clearance but
      subsequent recurrence of their parasitemias. Genotyping of the recurrent and Day
      0 parasitemias differed, suggesting either new infections or relapses of liver
      hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax
      was sensitive to chloroquine and halofantrine. Genotyping was useful for
      differentiating the recurrent vivax parasitemias.

PMID- 11304057
TI  - Limited potential for transmission of live dengue virus vaccine candidates by
      Aedes aegypti and Aedes albopictus.
AB  - To evaluate the transmission risk of four live dengue (DEN) vaccine candidates
      developed by the U.S. Army (DEN-1, 45AZ5 PDK 20; DEN-2, S16803 PDK 50; DEN-3,
      CH53489 PDK 20; and DEN-4, 341750 PDK 20), we tested 3,010 Aedes aegypti and
      1,576 Aedes albopictus mosquitoes blood-fed on 21 volunteers who had been
      administered one of the four vaccine candidates or the licensed yellow fever (YF)
      vaccine (17D). We used an indirect immunofluorescence assay (IFA) to detect DEN
      or YF viral antigen in the heads of mosquitoes. Corresponding to the lack of a
      detectable viremia among volunteers inoculated 8-13 days previously with live DEN
      1 or DEN-2 vaccine candidates, only six mosquitoes developed disseminated
      infections after feeding on these volunteers. These six mosquitoes included 4 of
      247 Ae. albopictus fed on volunteers inoculated with the DEN-1 vaccine candidate
      and 2 of 528 Ae. aegypti fed on volunteers inoculated with the DEN-2 vaccine
      candidate. Infection was confirmed in each of these IFA-positive mosquitoes by
      isolating infectious virus from the mosquito's body in Vero-cell culture. None of
      the 1,252 or the 969 mosquitoes fed on DEN-3 or DEN-4 recipients, respectively,
      were infected. Overall, dissemination rates in Ae. albopictus and Ae. aegypti
      were low. Dissemination rates were 0.5%, 0.3%, < 0.1%, and < 0.1% for the DEN-1
      through DEN-4 vaccine candidates, respectively. Because of the observed low
      dissemination rates, it is unlikely that these vaccine viruses would be
      transmitted under natural conditions.

PMID- 11304058
TI  - First isolation of the Rift Valley fever virus from Culex poicilipes (Diptera:
      Culicidae) in nature.
AB  - Following the reemergence of Rift Valley fever (RVF) virus in southeastern
      Mauritania in 1998, an entomological survey was undertaken in the boundary area
      in Senegal to assess the extent of the virus circulation. During this study, RVF
      virus (36 strains) was isolated for the first time from Culex poicilipes in
      nature. The possible role of Cx. poicilipes as an RVF vector is discussed
      regarding its biology and ecology.

PMID- 11304059
TI  - Hyperreactive onchocerciasis exhibits reduced arachidonate and linoleate levels
      in serum triglycerides.
AB  - The mechanism by which the minority of patients with onchocerciasis exhibiting
      the hyperreactive (sowda) form of the disease may be able to kill the
      microfilariae of Onchocerca volvulus is still poorly understood. In this study,
      the relative amounts of arachidonate and linoleate in serum phospholipids and
      triglycerides were investigated by gas chromatography both in patients infected
      with O. volvulus who exhibited either a hyperreactive or a generalized form of
      onchocerciasis and in persons with no filarial infections. Remarkable differences
      were observed in the serum triglycerides but not in the phospholipids. In
      comparison to persons without any filarial infection, significantly lower
      relative amounts of arachidonate--indicated by elevated triene-tetraene ratios-
      and of linoleate--indicated by lower diene + tetraene - triene values--were
      detected in patients with hyperreactive onchocerciasis, and less pronounced
      differences were found in persons with generalized onchocerciasis. The
      relationship between reduced amounts of arachidonate and linoleate in serum
      triglycerides and possible implications on the eicosanoid production in the host
      parasite relationship leading to parasite elimination are discussed.

PMID- 11304060
TI  - Markers of enteric inflammation in enteroaggregative Escherichia coli diarrhea in
      travelers.
AB  - As part of a traveler's diarrhea study carried out in Guadalajara, Mexico, and
      Goa, India, we conducted a case control study to evaluate fecal markers of
      enteric inflammation in three groups. Forty-five cases of enteroaggregative
      Escherichia coli (EAEC) diarrhea were compared to 56 controls with
      enterotoxigenic E. coli (ETEC) diarrhea, and 126 controls with diarrhea without
      identifiable pathogens. For EAEC cases we found fecal leukocytes, occult blood,
      and lactoferrin in 13 (28.9%), 14 (31.1%), and 27 (60.0%) patients, respectively;
      for ETEC controls they were 15 (26.8%), 16 (28.6%), and 15 (26.8%) respectively;
      and for patients without identifiable pathogens 19 (15.1%), 34 (27.0%) and 27
      (21.4%) were seen for the presence of a positive fecal lactoferrin test in EAEC
      cases was statistically significant compared to both control groups. The study
      provides evidence that EAEC infection is associated with an intestinal
      inflammatory response.

PMID- 11304061
TI  - The incubation period of hantavirus pulmonary syndrome.
AB  - In 1993 Sin Nombre virus was recognized as the cause of hantavirus pulmonary
      syndrome (HPS) and the deer mouse (Peromyscus maniculatus) was identified as the
      reservoir host. Surveillance by the Centers for Disease Control and Prevention
      and state health departments includes investigation to determine the likely
      site(s) and activities that led to infection, an environmental assessment of the
      home and workplace, and possibly rodent trappings at these sites. As of December
      31, 1998, there were 200 confirmed cases from 30 states (43% case-fatality
      ratio). The national HPS case registry was examined to determine the incubation
      period of HPS. Review of 11 case-patients with well-defined and isolated exposure
      to rodents suggests that the incubation period of HPS is 9 to 33 days, with a
      median of 14-17 days. Case investigations allow a better understanding of the
      incubation time of HPS and may define high-risk behaviors that can be targeted
      for intervention.

PMID- 11304062
TI  - A possible role of bats as a blood source for the Leishmania vector Lutzomyia
      longipalpis (Diptera: Psychodidae).
AB  - Some evidence suggests that bats may provide an alternative blood source for
      Lutzomyia longipalpis, the main vector of American visceral leishmaniasis.
      Feeding trials were conducted to determine whether L. longipalpis feeds on
      captive bats. The high feeding success indicated that L. longipalpis is capable
      of feeding on at least four species of bats. Implications for the epidemiology of
      leishmaniases are discussed.

PMID- 11304063
TI  - Serologic responses of Korean soldiers serving in malaria-endemic areas during a
      recent outbreak of Plasmodium vivax.
AB  - Anti-Pv200 antibody levels were assessed in samples from endemic areas of
      Plasmodium vivax malaria in the Republic of Korea (ROK), using an indirect enzyme
      linked immunosorbent assay (ELISA) method. Asymptomatic carriers of P. vivax were
      detected using nested polymerase chain reaction (PCR) of blood samples. Anti
      Pv200 antibody levels in 20 vivax malaria patients (optical density +/- standard
      deviation [OD +/- SD] values 1.85 +/- 0.29 of IgG isotype and 1.33 +/- 1.33 of
      IgM isotype) were markedly higher than those of uninfected, malaria-naive
      controls (0.08 +/- 0.16 of IgG isotype and 0.04 +/- 0.04 of IgM isotype).
      Antibody levels for 7 out of 8 soldiers with a recent malaria infection were
      sustained above the cut-off values for 4 months after successful treatment.
      Analysis of serum collected from 40 healthy, asymptomatic soldiers who had a P.
      vivax malaria attack within 3 months after our sampling, revealed 11 antibody
      positive samples (27.5%), compared to 5 positive samples (12.5%) collected from a
      random selection of 40 soldiers. Among a larger pool of 1,713 soldiers who had
      served in high-risk areas for P. vivax transmission, 15% were antibody positive.
      Among 1,000 blood samples from asymptomatic soldiers who had served in the high
      risk areas, 4 samples (0.4%) were parasite positive, as determined by nested PCR.
      Our results show that anti-Pv200 antibody levels can provide useful information
      in the late diagnosis of P. vivax malaria infection in a previously naive
      population and also in large seroepidemiologic studies. Furthermore, our results
      suggest that asymptomatic P. vivax carriers could be important in the current
      outbreak of malaria in Korea.

PMID- 11304064
TI  - Dry season refugia of malaria-transmitting mosquitoes in a dry savannah zone of
      east Africa.
AB  - Dry season survival of Anopheles funestus, Anopheles gambiae and Anopheles
      arabiensis in the Kilombero valley a dry savannah zone of east Africa, was
      investigated with over 400 collections from 23 areas, covering 300 sq km of the
      valley. Anopheles gambiae was found only in association with humans, in forested
      areas of high annual rainfall, while An. funestus occurred at high densities at
      the valley edge where large non-moving bodies of water remained. A large
      population of An. arabiensis was present along the river system throughout the
      middle of the valley, and mosquitoes probably derived from this population were
      occasionally caught in villages bordering the valley. No evidence was obtained of
      aestivation in any mosquito species. Anopheles gambiae was the most long lived,
      6.3% compared to 2.0% of the An. arabiensis and 4% of the An. funestus surviving
      for four or more gonotrophic cycles, the approximate duration of the extrinsic
      cycle of most malaria parasites. Oocysts of malaria parasites were found in 5.4%
      of An. funestus and 2.3% of An. arabiensis from villages. Oocyst rates in An.
      funestus differed significantly between areas but not between houses within
      areas. Anopheles funestus is the most important dry season malaria vector in the
      valley, and remains in foci closely associated with groups of houses. All three
      species survive at high densities but as otherwise hidden refugia populations.

PMID- 11304065
TI  - Large epidemics of hemorrhagic fevers in Mexico 1545-1815.
AB  - In 1545, twenty-four years after the Spanish conquest of the Aztec empire, an
      epidemic of a malignant form of a hemorrhagic fever appeared in the highlands of
      Mexico. The illness was characterized by high fever, headache, and bleeding from
      the nose, ears, and mouth, accompanied by jaundice, severe abdominal and thoracic
      pain as well as acute neurological manifestations. The disease was highly lethal
      and lasted three to four days. It attacked primarily the native population,
      leaving the Spaniards almost unaffected. The hemorrhagic fevers remained in the
      area for three centuries and the etiologic agent is still unknown. In this report
      we describe, and now that more information is available, analyze four epidemics
      that occurred in Mexico during the colonial period with a focus on the epidemic
      of 1576 which killed 45% of the entire population of Mexico. It is important to
      retrieve such diseases and the epidemics they caused from their purely historical
      context and consider the reality that if they were to reemerge, they are
      potentially dangerous.

PMID- 11304066
TI  - Human immune response to sand fly salivary gland antigens: a useful
      epidemiological marker?
AB  - Antibody (IgG) responses to salivary gland homogenate and to a recombinant
      salivary protein from the sand fly Lutzomyia longipalpis were investigated using
      sera from children living in an endemic area of visceral leishmaniasis in Brazil.
      We classified children into four groups according to their responses to
      Leishmania antigen: (Group I) positive serology and positive delayed type
      hypersensitivity (DTH), (Group II) positive serology and negative DTH, (Group
      III) negative serology and positive DTH, and (Group IV) negative serology and
      negative DTH. A highly significant correlation was found between anti-salivary
      gland IgG levels and DTH responses. An L. longipalpis salivary recombinant
      protein used as an antigen in an enzyme-linked immuno sorbent assay (ELISA) gave
      a significant but different result. A positive correlation was found between anti
      Leishmania IgG and anti-recombinant protein IgG titers. The results indicate that
      sand fly salivary proteins may be of relevance to the study the epidemiology of
      leishmaniasis.

PMID- 11304067
TI  - Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red
      blood cell-associated antigens in two Senegalese villages with different
      transmission conditions.
AB  - The recombinant R23, PfEB200, and GST-5 antigens derive from conserved antigens
      associated with the Plasmodium falciparum-infected erythrocyte membrane. They
      were identified as targets of protective antibodies in the Saimiri sciureus
      model. We have assessed here the humoral response to these antigens in humans.
      Cross-sectional surveys were conducted in two Senegalese villages with different
      levels of endemicity. The prevalence of specific IgG and IgM was similar and
      influenced by age in both localities. The anti-R23 antibodies decreased after the
      rainy season, particularly in the children less than ten years old. The anti
      PfEB200 response did not show significant seasonal variation. The anti-GST-5
      response increased in both the less-than 10-year-old and the greater-than 10-year
      old groups after the rainy season in Dielmo, but only in the Ndiop villagers who
      were more than 10-years-old. Thus, antigen-specific seasonal variations of
      antibody levels were influenced differently by age in both villages. The isotype
      distribution was antigen-specific and differed for both seasons.

PMID- 11304068
TI  - Alcohol-related brain damage--the concerns of the Mental Welfare Commission.
AB  - Scottish mental health legislation permits 'guardianship' for certain mentally
      impaired individuals, which imposes a requirement on place of residence, access
      and attendance at specified services for treatment and rehabilitation. The use of
      guardianship for alcohol-related brain damage increased steeply in the years 1993
      1998. Possible explanations include: (1) increased prevalence or diagnosis of
      these conditions; (2) reduction of hospital beds; (3) a trend towards diminishing
      family and social support; (4) increased social work involvement in caring for
      such individuals; (5) increased consideration of the use of guardianship; (6) new
      private residential services; (7) lack of interest in the condition by existing
      services. There have been legal and clinical concerns about such individuals
      under guardianship relating to quality of ongoing clinical assessment, need for
      specific treatment and for the management of associated psychiatric illness,
      issues over control of drinking and control of personal finances, uncertainty
      over the use of restraint, and need for programmes helping the individual's
      progress towards independent living.

PMID- 11304069
TI  - Wernicke-Korsakoff syndrome in head injury: a missed insult.
AB  - A survey of the use of thiamine in patients at risk from Wernicke-Korsakoff
      syndrome (WKS) in Scottish specialist neurosurgical units, and a 2-year
      retrospective study of 218 at-risk patients admitted to a regional neurosurgical
      unit with a head injury were undertaken. Although responses to the survey
      indicated otherwise, the study revealed that there was no consistent practice
      regarding thiamine administration. Overall, 20.6% of patients received thiamine,
      with an alcohol history being the only factor correlating with thiamine
      administration. Of known alcoholics and heavy drinkers, 56.1% and 26.2%
      respectively received thiamine as in-patients; 44.5% of patients received
      additional carbohydrate loads in the form of i.v. dextrose or parenteral
      nutrition, but only 28.9% of these received thiamine as well. Although the actual
      thiamine status of these patients was not known, given the difficulties of
      diagnosing WKS in the presence of a head injury, the conclusion is that written
      protocols are needed in units to ensure that head injury patients at risk of WKS
      receive appropriate thiamine treatment or prophylaxis.

PMID- 11304070
TI  - Prevention and treatment of Wernicke-Korsakoff syndrome.
AB  - Wernicke's encephalopathy (WE) is both common and associated with high morbidity
      and mortality and yet there is evidence that appropriate and effective
      prophylaxis and treatment are often not given. Effective treatment and
      prophylaxis may only be achieved by use of parenteral vitamin supplements, since
      oral supplements are not absorbed in significant amounts. Although there are rare
      anaphylactoid reactions associated with the use of parenteral thiamine
      preparations, the risks and consequences of inadequate prophylaxis and treatment,
      in appropriately targeted groups of patients, are far greater. It is therefore
      proposed that all in-patient alcohol withdrawal should be covered by prophylactic
      use of parenteral thiamine, that there should be a low threshold for making a
      presumptive diagnosis of WE, and that there is a need for guidelines to assist
      physicians in appropriate management of this common clinical problem.

PMID- 11304071
TI  - Mechanisms of vitamin deficiency in chronic alcohol misusers and the development
      of the Wernicke-Korsakoff syndrome.
AB  - The classic signs of vitamin deficiency only occur in states of extreme depletion
      and are unreliable indicators for early treatment or prophylaxis of alcoholic
      patients at risk. Post-mortem findings demonstrate that thiamine (vitamin B1)
      deficiency sufficient to cause irreversible brain damage is not diagnosed ante
      mortem in 80-90% of these patients. The causes of vitamin deficiency are reviewed
      with special attention to the inhibition of oral thiamine hydrochloride
      absorption in man caused by malnutrition present in alcoholic patients or by the
      direct effects of ethanol on intestinal transport. As the condition of the
      patient misusing alcohol progresses, damage to brain, liver, gastrointestinal
      tract, and pancreas continue (with other factors discussed) to further compromise
      the patient. Decreased intake, malabsorption, reduced storage, and impaired
      utilization further reduce the chances of unaided recovery. Failure of large oral
      doses of thiamine hydrochloride to provide an effective treatment for Wernicke's
      encephalopathy emphasizes the need for adequate and rapid replacement of depleted
      brain thiamine levels by repeated parenteral therapy in adequate doses.

PMID- 11304072
TI  - Wernicke-Korsakoff syndrome and the use of brain imaging.
AB  - The proportion of patients with Korsakoff psychosis (KP) who have a history of
      Wernicke's encephalopathy is smaller in recent studies compared to previous
      studies. Neuropsychological tests, magnetic resonance imaging (MRI), and single
      photon emission computed tomography were conducted in eight patients with KP,
      only four of whom had had a documented Wernicke episode. All subjects showed
      amnesia without intellectual deterioration. MRI abnormalities were seen in each
      group to the same extent (atrophy of mammillary bodies, to a less extent thalamus
      and some generalized gyral atrophy). No MRI measure differentiated the groups.
      Cerebral blood flow showed reduction of flow to the anterior temporal regions
      bilaterally, extending to the parietal lobes, to the same degree in each group.
      Despite the small number of patients examined, the study supports the belief that
      patients with an insidious onset of KP have the same pathology as those with
      classical Wernicke-Korsakoff syndrome. This raises the question of whether
      episodes of alcohol withdrawal without adequate thiamine protection result in
      occasionally subclinical Wernicke's events, followed by a subsequently
      diagnosable KP.

PMID- 11304073
TI  - Korsakoff's psychosis in Scotland: evidence for increased prevalence and regional
      variation.
AB  - Surveys of new long-stay mental hospital patients in Scotland find that 9% have a
      diagnosis of alcohol-related brain damage, mainly Korsakoff's psychosis (KP),
      whereas the rate was 5% in the old long-stay patients. The national hospital
      database shows a rise in rates of KP in figures for discharge diagnosis and for
      diagnosis of hospital residents during the past three decades. There is an
      argument for more specialized provision given the significance of this group of
      patients.

PMID- 11304074
TI  - Does perception of biological motion rely on specific brain regions?
AB  - Perception of biological motions plays a major adaptive role in identifying,
      interpreting, and predicting the actions of others. It may therefore be
      hypothesized that the perception of biological motions is subserved by a specific
      neural network. Here we used fMRI to verify this hypothesis. In a group of 10
      healthy volunteers, we explored the hemodynamic responses to seven types of
      visual motion displays: drifting random dots, random dot cube, random dot cube
      with masking elements, upright point-light walker, inverted point-light walker,
      upright point-light walker display with masking elements, and inverted point
      light walker display with masking elements. A gradient in activation was observed
      in the occipitotemporal junction. The responses to rigid motion were localized
      posteriorly to those responses elicited by nonrigid motions. Our results
      demonstrate that in addition to the posterior portion of superior temporal
      sulcus, the left intraparietal cortex is involved in the perception of nonrigid
      biological motions.

PMID- 11304075
TI  - Maturation of widely distributed brain function subserves cognitive development.
AB  - Cognitive and brain maturational changes continue throughout late childhood and
      adolescence. During this time, increasing cognitive control over behavior
      enhances the voluntary suppression of reflexive/impulsive response tendencies.
      Recently, with the advent of functional MRI, it has become possible to
      characterize changes in brain activity during cognitive development. In order to
      investigate the cognitive and brain maturation subserving the ability to
      voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in
      an oculomotor response-suppression task. Behavioral results indicated that adult
      like ability to inhibit prepotent responses matured gradually through childhood
      and adolescence. Functional MRI results indicated that brain activation in
      frontal, parietal, striatal, and thalamic regions increased progressively from
      childhood to adulthood. Prefrontal cortex was more active in adolescents than in
      children or adults; adults demonstrated greater activation in the lateral
      cerebellum than younger subjects. These results suggest that efficient top-down
      modulation of reflexive acts may not be fully developed until adulthood and
      provide evidence that maturation of function across widely distributed brain
      regions lays the groundwork for enhanced voluntary control of behavior during
      cognitive development.

PMID- 11304076
TI  - Stimulus-response incompatibility activates cortex proximate to three eye fields.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate cortical
      activation during the performance of three oculomotor tasks that impose
      increasing levels of cognitive demand. (1) In a visually guided saccade (VGS)
      task, subjects made saccades to flashed targets. (2) In a compatible task,
      subjects made leftward and rightward saccades in response to foveal presentation
      of the uppercase words "LEFT" or "RIGHT." (3) In a mixed task, subjects made
      rightward saccades in response to the lowercase word "left" and leftward saccades
      in response to the lowercase word "right" on incompatible trials (60%). The
      remaining 40% of trials required compatible responses to uppercase words. The VGS
      and compatible tasks, when compared to fixation, activated the three cortical eye
      fields: the supplementary eye field (SEF), the frontal eye field (FEF), and the
      parietal eye field (PEF). The mixed task, when compared to the compatible task,
      activated three additional cortical regions proximate to the three eye fields:
      (1) rostral to the SEF in medial frontal cortex; (2) rostral to the FEF in
      dorsolateral prefrontal cortex (DLPFC); (3) rostral and lateral to the PEF in
      posterior parietal cortex. These areas may contribute to the suppression of
      prepotent responses and in holding novel visuomotor associations in working
      memory.

PMID- 11304077
TI  - Landmark-based morphometrics of the normal adult brain using MRI.
AB  - We describe the application of statistical shape analysis to homologous landmarks
      on the cortical surface of the adult human brain. Statistical shape analysis has
      a sound theoretical basis. Landmarks are identified on the surface of a 3-D
      reconstruction of the segmented cortical surface from magnetic resonance image
      (MRI) data. Using publicly available software (morphologika) the location and
      size dependence of the landmarks are removed and the differences in landmark
      distribution across subjects are analysed using principal component analysis.
      These differences, representing shape differences between subjects, can be
      visually assessed using wireframe models and transformation grids. The MRI data
      of 58 adult brains (27 female and 15 left handed) were examined. Shape
      differences in the whole brain are described which concern the relative
      orientation of frontal lobe sulci. Analysis of all 116 hemispheres revealed a
      statistically significant difference (P < 0.001) between left and right
      hemispheres. This finding was significant for right- but not left-handed subjects
      alone. No other significant age, gender, handedness, or brain-size correlations
      with shape differences were found.

PMID- 11304078
TI  - Gray matter-changes and correlates of disease severity in schizophrenia: a
      statistical parametric mapping study.
AB  - Voxel-based morphometry has recently been used successfully to detect gray matter
      volume reductions in schizophrenic patients. The aim of the present study was to
      confirm the findings on gray-matter changes and to complement these by applying
      the methodology to CSF-differences. Also, we wanted to determine whether a
      correlation exists between a clinically defined parameter of disease severity and
      brain morphology in schizophrenic patients. We investigated 48 schizophrenic
      patients and compared them with 48 strictly age- and sex-matched controls. High
      resolution whole-brain MR-images were segmented and analyzed using SPM99. In a
      further analysis, the covariate effect of the global assessment of functioning
      score (GAF) was calculated. Main findings were (i) left-dominant frontal,
      temporal, and insular GM-reductions and (ii) GM-increases in schizophrenic
      patients in the right basal ganglia and bilaterally in the superior cerebellum;
      (iii) CSF-space increases in patients complementary to some GM-reductions; (iv) a
      correlation between the GAF-score and local GM-volume in the left inferior
      frontal and inferior parietal lobe of schizophrenic patients. This study confirms
      and extends some earlier findings on GM-reduction and detected distinct GM
      increases in schizophrenic patients. These changes were corroborated by
      complementary CSF-increases. Most importantly, a correlation could be established
      between two particular gray matter-regions and the overall disease severity, with
      more severely ill patients displaying a local GM-deficit. These findings may be
      of potentially large importance for both the future interpretation and design of
      neuroimaging studies in schizophrenia and the further elucidation of possible
      pathophysiological processes occurring in this disease.

PMID- 11304079
TI  - Different ipsilateral representations for distal and proximal movements in the
      sensorimotor cortex: activation and deactivation patterns.
AB  - Each hemisphere is known to be also involved in controlling the ipsilateral arm,
      but with an asymmetry favoring the dominant hemisphere. However, the relative
      role of primary and secondary motor areas in ipsilateral control is not well
      defined. We used whole brain functional magnetic resonance imaging in healthy
      human subjects to differentiate between contributions from primary and secondary
      areas during discrete unilateral distal finger and proximal shoulder movements.
      It was found that ipsilateral distal movements activated secondary areas only,
      while sparing or even significantly deactivating the primary sensorimotor cortex.
      Ipsilateral proximal movements substantially activated both SM1 and secondary
      areas. A newly defined small territory within the precentral gyrus, extending
      from the premotor cortex and intruding toward SM1, showed an activation pattern
      corresponding to secondary motor areas. Finally, the effects of hemispheric
      dominance were confirmed, but attributed exclusively to secondary areas. These
      new imaging findings agree well with functional requirements as well as
      established anatomical and neurophysiological data.

PMID- 11304080
TI  - The neural system underlying Chinese logograph reading.
AB  - Written Chinese as logographic script differs notably from alphabets such as
      English in visual form, orthography, phonology, and semantics. Thus, research on
      the Chinese language is important to advance our understanding of the
      universality and particularity of the organization of language systems in the
      brain. In this study, we examine the neural systems associated with logographic
      reading using functional magnetic resonance imaging. Two experimental tasks were
      devised, one based on semantic decision and the other on homophone decision.
      Compared to the fixation baseline, peak activations resulting from semantic as
      well as homophony decisions were localized in the left middle frontal gyrus (BA
      9). Left inferior frontal cortex also mediated Chinese processing. In addition,
      more right hemisphere cortical regions (i.e., BAs 47/45, 7, 40/39, and the right
      visual system) were involved in reading Chinese relative to reading English. This
      is attributed to the square shape of the logograph which requires an elaborated
      analysis of the spatial information and locations of various strokes comprising
      the logographic character. We suggest that the left middle frontal area (BA 9)
      coordinates and integrates the intensive visuospatial analysis demanded by
      logographs' square configuration and the semantic (or phonological) analysis
      required by the present experimental tasks. Our study has implicated brain
      regions common to both logographic and alphabetic languages as well as brain
      regions specialized in processing logographs.

PMID- 11304081
TI  - Automated hippocampal segmentation by regional fluid registration of serial MRI:
      validation and application in Alzheimer's disease.
AB  - The application of voxel-level three-dimensional registration to serial magnetic
      resonance imaging (MRI) is described. This fluid registration determines
      deformation fields modeling brain change, which are consistent with a model
      describing a viscous fluid. The objective was to validate the measurement of
      hippocampal volumetric change by fluid registration in Alzheimer's disease (AD)
      against current methodologies. The hippocampus was chosen for this study because
      it is difficult to measure reproducibly by manual segmentation and is widely
      studied; however, the technique is applicable to any structure which can be
      delineated on a scan. First, suitable values for the viscosity-body-force-ratio,
      alpha (0.01), and the number of iterations (300), were established and the
      convergence, repeatability, linearity, and accuracy investigated and compared
      with expert manual segmentation. A simple model of hippocampal atrophy was used
      to compare simulated volumetric change against that obtained by fluid
      registration. Finally the serial segmentation was compared with the current gold
      standard technique-expert human labeling with a volume repeatability of
      approximately 4%-in 27 subjects (15 normal controls, 12 clinically diagnosed with
      Alzheimer's disease). The scan-rescan volumetric consistency of serial
      segmentation by fluid-registration was shown to be superior to human serial
      segmentors ( approximately 2%). The mean absolute volume difference between fluid
      and manual segmentation was 0.7%. Fluid registration has potential importance for
      tracking longitudinal structural changes in brain particularly in the context of
      the clinical trial where large numbers of subjects may have multiple MR scans.

PMID- 11304082
TI  - Magnetic resonance image tissue classification using a partial volume model.
AB  - We describe a sequence of low-level operations to isolate and classify brain
      tissue within T1-weighted magnetic resonance images (MRI). Our method first
      removes nonbrain tissue using a combination of anisotropic diffusion filtering,
      edge detection, and mathematical morphology. We compensate for image
      nonuniformities due to magnetic field inhomogeneities by fitting a tricubic B
      spline gain field to local estimates of the image nonuniformity spaced throughout
      the MRI volume. The local estimates are computed by fitting a partial volume
      tissue measurement model to histograms of neighborhoods about each estimate
      point. The measurement model uses mean tissue intensity and noise variance values
      computed from the global image and a multiplicative bias parameter that is
      estimated for each region during the histogram fit. Voxels in the intensity
      normalized image are then classified into six tissue types using a maximum a
      posteriori classifier. This classifier combines the partial volume tissue
      measurement model with a Gibbs prior that models the spatial properties of the
      brain. We validate each stage of our algorithm on real and phantom data. Using
      data from the 20 normal MRI brain data sets of the Internet Brain Segmentation
      Repository, our method achieved average kappa indices of kappa = 0.746 +/- 0.114
      for gray matter (GM) and kappa = 0.798 +/- 0.089 for white matter (WM) compared
      to expert labeled data. Our method achieved average kappa indices kappa = 0.893
      +/- 0.041 for GM and kappa = 0.928 +/- 0.039 for WM compared to the ground truth
      labeling on 12 volumes from the Montreal Neurological Institute's BrainWeb
      phantom.

PMID- 11304083
TI  - Activation reduction in anterior temporal cortices during repeated recognition of
      faces of personal acquaintances.
AB  - Repeated recognition of the face of a familiar individual is known to show
      semantic repetition priming effect. In this study, normal subjects were
      repeatedly presented faces of their colleagues, and the effect of repetition on
      the regional cerebral blood flow change was measured using positron emission
      tomography. They repeated a set of three tasks: the familiar-face detection (F)
      task, the facial direction discrimination (D) task, and the perceptual control
      (C) task. During five repetitions of the F task, familiar faces were presented
      six times from different views in a pseudorandom order. Activation reduction
      through the repetition of the F tasks was observed in the bilateral anterior
      (anterolateral to the polar region) temporal cortices which are suggested to be
      involved in the access to the long-term memory concerning people. The bilateral
      amygdala, the hypothalamus, and the medial frontal cortices, were constantly
      activated during the F tasks, and considered to be associated with the behavioral
      significance of the presented familiar faces. Constant activation was also
      observed in the bilateral occipitotemporal regions and fusiform gyri and the
      right medial temporal regions during perception of the faces, and in the left
      medial temporal regions during the facial familiarity detection task, which are
      consistent with the results of previous functional brain imaging studies. The
      results have provided further information about the functional segregation of the
      anterior temporal regions in face recognition and long-term memory.

PMID- 11304084
TI  - Dopamine D2 receptors in the insular cortex and the personality trait of novelty
      seeking.
AB  - Human personality has been considered to have a neurochemical background. We
      examined the relation between extrastriatal dopamine D2 receptor binding in
      living human brain and the personality trait of novelty seeking that has been
      proposed to be related to dopaminergic function in the brain. We measured
      extrastriatal dopamine D2 receptors of 24 healthy young male subjects using
      [(11)C]FLB 457 positron emission tomography. The personality trait of each
      subject was assessed by the Temperament and Character Inventory (TCI).
      Correlation of dopamine D2 receptor binding with novelty seeking was calculated
      using region-of-interest analysis and statistical parametric mapping based on the
      binding potential images generated using a reference tissue model. A significant
      negative correlation was observed between binding potential values and the
      novelty seeking scores on TCI in the right insular cortex. No significant
      correlation was observed in any other region. Our result indicates that there is
      a significant association between dopamine D2 receptor binding and the human
      novelty seeking trait in the right insular cortex.

PMID- 11304085
TI  - Perfusion brain SPECT and statistical parametric mapping analysis indicate that
      apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented
      patients.
AB  - Apathy is the most frequent behavioral symptom in Alzheimer's disease and is also
      frequently reported in other brain organic disorders occurring in the elderly.
      Based on the literature, we hypothesized that apathy was related to an anterior
      cingulate hypofunction. Forty-one subjects were studied. According to ICD 10
      diagnostic criteria, 28 patients had Alzheimer dementia (demented: diagnostic
      group 1), and 13 had organic personality disorders or mild cognitive impairment
      not attributable to dementia (nondemented: diagnostic group 2). Apathy was
      evaluated by the Neuro-Psychiatric Inventory. As a result each diagnostic group
      was divided into two symptomatic subgroups: apathetic or nonapathetic. Brain
      perfusion was measured by (99m)Tc-labeled bicisate (ECD) brain SPECT and the
      images were compared using Statistical Parametric Mapping (SPM96). We began by
      comparing apathetic vs nonapathetic patients, whatever their diagnostic group
      (whole population), then analyzed them within each group. Twenty-one subjects
      were apathetic (14 in group 1 and 7 in group 2) and 20 were not (14 in group 1
      and 6 in group 2). For the whole population, the Z map showed a significant
      decrease in ECD uptake for the apathetic patients in the anterior cingulate (P <
      0.002) bilaterally. This area was also identified as hypoactive by SPM analysis
      in the demented (P < 0.035) and in the nondemented (P < 0.02) apathetic patient
      groups. Finally, conjunction analysis indicated that the anterior cingulate was
      the common hypoactive structure of the two apathetic subgroups (Z = 4.35, P <
      0.0009). These results point to a close relationship between apathy and the
      anterior cingulate region.

PMID- 11304086
TI  - Modeling geometric deformations in EPI time series.
AB  - Even after realignment there is residual movement-related variance present in
      fMRI time-series, causing loss of sensitivity and, potentially, also specificity.
      One cause is the differential deformation of the sampling matrix, by field
      inhomogeneities, at different object positions, i.e., a movement-by-inhomogeneity
      interaction. This has been addressed previously by using empirical field
      measurements. In the present paper we suggest a forward model of how data is
      affected by an inhomogeneous field at different object positions. From this model
      we derive a method to solve the inverse problem of estimating the field
      inhomogeneities and their derivatives with respect to object position, directly
      from the EPI data and estimated realignment parameters. The field is modeled as a
      linear combination of cosine basis fields, which facilitates a fast way of
      implementing the necessary matrix operations. Simulations suggest that the
      solution is tractable and that the fields are estimable given the deformed images
      and knowledge of the relative positions at which they have been acquired. An
      experiment on a subject performing voluntary movements in the scanner yielded
      plausible estimates of the deformation fields and their application to "unwarp"
      the time series significantly reduced movement-related variance.

PMID- 11304087
TI  - Estimation of the number of "true" null hypotheses in multivariate analysis of
      neuroimaging data.
AB  - The repeated testing of a null univariate hypothesis in each of many sites
      (either regions of interest or voxels) is a common approach to the statistical
      analysis of brain functional images. Procedures, such as the Bonferroni, are
      available to maintain the Type I error of the set of tests at a specified level.
      An initial assumption of these methods is a "global null hypothesis," i.e., the
      statistics computed on each site are assumed to be generated by null
      distributions. This framework may be too conservative when a significant
      proportion of the sites is affected by the experimental manipulation. This report
      presents the development of a rigorous statistical procedure for use with a
      previously reported graphical method, the P plot, for estimation of the number of
      "true" null hypotheses in the set. This estimate can then be used to sharpen
      existing multiple comparison procedures. Performance of the P plot method in the
      multiple comparison problem is investigated in simulation studies and in the
      analysis of autoradiographic data.

PMID- 11304088
TI  - Qualitative and quantitative evaluation of six algorithms for correcting
      intensity nonuniformity effects.
AB  - The desire to correct intensity nonuniformity in magnetic resonance images has
      led to the proliferation of nonuniformity-correction (NUC) algorithms with
      different theoretical underpinnings. In order to provide end users with a
      rational basis for selecting a given algorithm for a specific neuroscientific
      application, we evaluated the performance of six NUC algorithms. We used
      simulated and real MRI data volumes, including six repeat scans of the same
      subject, in order to rank the accuracy, precision, and stability of the
      nonuniformity corrections. We also compared algorithms using data volumes from
      different subjects and different (1.5T and 3.0T) MRI scanners in order to relate
      differences in algorithmic performance to intersubject variability and/or
      differences in scanner performance. In phantom studies, the correlation of the
      extracted with the applied nonuniformity was highest in the transaxial (left-to
      right) direction and lowest in the axial (top-to-bottom) direction. Two of the
      six algorithms demonstrated a high degree of stability, as measured by the
      iterative application of the algorithm to its corrected output. While none of the
      algorithms performed ideally under all circumstances, locally adaptive methods
      generally outperformed nonadaptive methods.

PMID- 11304089
TI  - Estimation of regional cerebral blood flow distribution in infants by near
      infrared topography using indocyanine green.
AB  - Near-infrared topography with indocyanine green was used to measure regional
      cerebral blood flow (rCBF) in the temporal lobes of infants. The mean rCBF in
      infants without neural abnormality was 14.5 +/- 3.1 ml/100 g/min, and the rCBFs
      in the fronto-temporal, temporal, and occipito-temporal regions were 15.1 +/-
      3.9, 15.4 +/- 3.3, and 14.6 +/- 3.3 ml/100 g/min, respectively. Moreover, in one
      asphyxiated infant with infarction and one infant with subdural and
      intracerebellar hemorrhage, it was demonstrated that the area of defective blood
      flow could be detected as well as it can by SPECT. This technique makes it
      possible to estimate rCBF distribution in infants at the bedside. Thus, in the
      future, evaluation of various neonatal illnesses should be feasible.

PMID- 11304090
TI  - Significant increase in young adults' snacking between 1977-1978 and 1994-1996
      represents a cause for concern!
AB  - BACKGROUND: Studies on children and adolescents suggest a large increase in the
      role of snacking; however, little is know about changes in the snacking behavior
      of young adults. METHODS: USDA's nationally representative surveys from 1977-1978
      to 1994-1996 are used to study snacking trends among 8,493 persons 19-29 years
      old. RESULTS: Snacking prevalence increased from 77 to 84% between 1977-1978 and
      1994-1996. The nutritional contribution of snacks to total daily energy intake
      went from 20 to 23%, primarily because energy consumed per snacking occasion
      increased by 26% and the number of snacks per day increased 14%. The mean daily
      caloric density (calorie per gram of food) of snacks increased from 1.05 to 1.32
      calories. The energy contribution of high-fat desserts to the total calories from
      snacking decreased (22 to 14%), however, this food group remained the most
      important source of energy. The energy contribution of high-fat salty snacks
      doubled. Sweetened and alcoholic beverages remained important energy
      contributors. CONCLUSION: This large increase in total energy and energy density
      of snacks among young adults in the United States may be contributing to our
      obesity epidemic.

PMID- 11304091
TI  - Page for patients. Hormone replacement therapy.

PMID- 11304092
TI  - Smoking status, reading level, and knowledge of tobacco effects among low-income
      pregnant women.
AB  - BACKGROUND: Smoking during pregnancy increases the health risks of the unborn
      child as well as the mother. Although smoking rates for the population as a whole
      have declined drastically in the past generation, since 1992 there has been an
      increase in smoking among women, teenagers, and adults living in poverty. The
      purpose of this study was to assess reading level, tobacco knowledge, attitudes,
      and practices of tobacco use among pregnant adult and adolescent women in the
      public health system in north Louisiana. METHODS: A convenience sample of 600
      pregnant women was interviewed in person in the Obstetrics Clinics at Louisiana
      State University Health Sciences Center at Shreveport and E.A. Conway in Monroe.
      The structured interview contained detailed questions about smoking practices,
      tobacco knowledge, and attitudes. Reading was assessed using the Rapid Estimate
      of Adult Literacy in Medicine. Smoking practices were assessed by self-report and
      verified by measuring urine cotinine levels. The Cochran-Mantel-Haenszel test was
      used to estimate the relationship between reading level and knowledge and
      attitude; multiple logistic regression was used to determine which variable(s)
      predicted current smoking practices. RESULTS: Knowledge about the effects of
      smoking and concern about the health effect of smoking on their baby varied
      significantly by reading level, with participants with higher reading levels
      having more knowledge and greater concern. Smoking practices did not vary by
      reading level even when race, age, and living with a smoker were controlled. Race
      was a significant determinant of smoking practices, with more white women
      reporting currently smoking during pregnancy than African Americans (34% vs 8%).
      CONCLUSIONS: Reading level was related to knowledge about health effects of
      smoking. Women with higher reading levels were also more concerned about the
      adverse health effects of smoking on themselves and their babies. However,
      reading level was not correlated with smoking prevalence. The most significant
      determinant of smoking was race (with whites smoking significantly more than
      African Americans).

PMID- 11304093
TI  - Intervention and policy issues related to children's exposure to environmental
      tobacco smoke.
AB  - BACKGROUND: Children's exposure to environmental tobacco smoke (ETS) is
      unacceptably high; almost 40% of children in the United States are regularly
      exposed to ETS. METHODS: This paper presents a review of the literature that
      evaluates interventions designed to reduce ETS exposure among young children. In
      addition, it presents the study design for Project KISS (Keeping Infants Safe
      from Smoke), an intervention designed to utilize exposure-related feedback to
      increase parents' motivation for ETS reduction and to reduce household ETS
      levels. Baseline data are presented to illustrate factors that should be
      addressed in ETS interventions. RESULTS: The literature review demonstrates the
      dearth of studies in the literature targeting ETS reduction among children.
      Participants in Project KISS believed that smoking had affected their children's
      health and were in later stages of motivational readiness to quit smoking than is
      typically observed. However, they face a number of challenges to smoking, such as
      high prevalence of nicotine dependence, high prevalence of living with other
      smokers, and socioeconomic and stress-related barriers. CONCLUSIONS: The policy
      implications of this research are discussed, and recommendations are made for
      future research.

PMID- 11304094
TI  - The effect of a community action intervention on adolescent smoking rates in
      rural australian towns: the CART project. Cancer Action in Rural Towns.
AB  - BACKGROUND: This paper describes one outcome of a randomized controlled trial of
      community action for cancer prevention, Cancer Action in Rural Towns. The aims
      are to [1] explore the effectiveness of community action in decreasing adolescent
      smoking in rural Australian towns; and [2] describe the relationship between
      adolescent smoking rates and demographic variables. METHODS: In 1992, 20 rural
      Australian towns were selected. Community action involved formation of community
      committees and utilization of access-point networks to initiate and maintain
      intervention strategies. Cross-sectional surveys of smoking behaviors for all
      Year 9 and Year 10 students (13-16 years) in each town were conducted pre- and
      posttest. The main outcome measure was self-reported smoking in the past 4 weeks.
      SUDAAN software was used to look at differences between treatment. RESULTS: The
      results showed strong secular trends toward increased adolescent smoking,
      regardless of treatment group, particularly for females. There was no significant
      intervention effect. CONCLUSIONS: Increasing adolescent smoking rates found in
      this and other studies highlight that the definitive strategy to stem the
      adolescent smoking epidemic has not been found. Hope may remain for recent
      legislative strategies, but rigorous evaluation is essential, and compliance with
      legislation should be carefully monitored.

PMID- 11304095
TI  - Smoking behavior and related factors among Japanese nursing students: a cohort
      study.
AB  - BACKGROUND: Although there have been several surveys on smoking behavior among
      Japanese nursing students, most have been cross-sectional studies. No
      longitudinal studies, such as a prospective cohort study, have ever been carried
      out. We therefore conducted a cohort study on, and analyzed smoking behavior and
      related factors among, Japanese nursing students. METHODS: A survey on smoking
      behavior using a confidential questionnaire was conducted on nursing students at
      two vocational schools of nursing and two nursing colleges/universities located
      in the Tokyo metropolitan area. Another survey was subsequently conducted in the
      same manner among the same subjects 1 year later. The surveys were conducted
      between 1997 and 1999. RESULTS: Over the 1-year period, the prevalence of smoking
      among nursing students increased by 10% for students at the vocational schools of
      nursing (n = 224) and by 3% for students at the nursing colleges/universities (n
      = 222). The average score for nicotine dependence for students who were daily
      smokers at both time points rose from 3.6 to 4.4 (P < 0.05). Two factors found to
      significantly predict smoking behavior were having friends who smoke and living
      alone. CONCLUSION: Smoking prevalence is increasing among Japanese nursing
      students. Smoking prevention and cessation interventions should be instituted in
      all nursing training programs.

PMID- 11304096
TI  - A comparison of breast cancer secondary prevention activities and satisfaction
      with access and communication issues in women 50 and over.
AB  - BACKGROUND: Between 1950 and 1990, the incidence of breast cancer increased about
      52% and the mortality rate increased 4%. Prevention programs (mammograms and
      clinical breast exams) can positively affect both cost control and mortality
      rates. Balancing the costs of preventive screening against the potential savings
      is a part of an ongoing debate centering on the age at which women should have
      yearly mammograms. Yet, if all agencies agree that women aged 50 and over should
      receive yearly mammograms, then why are so many women aged 50 and over not being
      screened? METHODS: Using previously validated instruments, this study surveyed
      residents of Spokane County, Washington. Respondents (1,850 returned of 2,600)
      were compared over time by demographic characteristics and by insurance type to
      identify any significant differences between those who had preventative screens
      and those who did not. Issues involving access to screening and communication
      with healthcare providers were also examined. RESULTS: Factors that affect
      whether women receive preventative screening include insurance type, provider
      type, long waiting times, and poor communication among the doctor, the staff, and
      the patient. CONCLUSION: The most important determinant to whether preventative
      screening is being conducted is the relationship between the patient and their
      healthcare provider.

PMID- 11304098
TI  - Smoking and mental health: cross-sectional and cohort studies in an occupational
      setting in Japan.
AB  - BACKGROUND: The relationship between smoking and mental health remains unclear.
      METHODS: We carried out a cross-sectional study and a cohort study on the
      possible association of smoking and mental health in 782 workers. Using a
      questionnaire including the 30-item General Health Questionnaire (GHQ-30) and
      items related to the smoking state, the association between smoking and mental
      health was evaluated separately in males and females. The subjects were
      classified into smokers and nonsmokers, and changes in the GHQ score during a 2
      year follow-up period were evaluated. To control potential confounding factors,
      multiple regression analyses were performed. RESULTS: The cross-sectional study
      showed no difference in the GHQ score between smokers and nonsmokers among males
      but a significantly higher GHQ score for smokers than nonsmokers among females.
      This difference among females was confirmed to be significant by multiple
      regression analysis. The 2-year cohort study showed a decrease in the GHQ score
      in each group and no reduction in the difference in the GHQ score between smokers
      and nonsmokers among females. CONCLUSIONS: No difference was observed in mental
      health between smokers and nonsmokers in males. However, in females, smokers
      showed poorer mental health than nonsmokers, and this difference remained
      unchanged even after 2 years.

PMID- 11304097
TI  - Reevaluation of the confounding effect of cigarette smoking on the relationship
      between alcohol use and lung cancer risk, with larynx cancer used as a positive
      control.
AB  - BACKGROUND: The effect of smoking on lung cancer risk has been well documented,
      while the effect of alcohol remains controversial. We examined the hypothesis
      that the apparent association between alcohol intake and lung cancer risk is
      fully due to the confounding effect of cigarette smoke. METHODS: Our sample of
      hospitalized patients included 2,953 male and 1,622 female lung cancer cases; 521
      male and 159 female larynx cancers cases; and 8,169 male and 4,154 female
      controls, admitted to participating hospitals between 1981 and 1994. All controls
      had been diagnosed with non-smoking-related diseases. Larynx cancer was used as a
      positive control for lung cancer. Relative risks were estimated through odds
      ratios, adjusted through multiple logistic regression. RESULTS: Although the odds
      ratios for alcohol had been significantly elevated prior to adjustment for
      smoking (OR = 2.4, 95% CI = 2.0-2.8), alcohol had no effect on lung cancer
      following this adjustment (OR = 1.2, 95% CI = 1.0-1.4). By contrast, the effect
      of alcohol on larynx cancer remained high even after adjustment for smoking (OR =
      5.6, 95% CI = 3.7-8.6). CONCLUSION: The often-reported association between
      alcohol and lung cancer risk can be fully explained by the confounding effect of
      cigarette use.

PMID- 11304099
TI  - Smoking cessation interventions among hospitalized patients: what have we
      learned?
AB  - BACKGROUND: We conducted a structured review of controlled studies on inpatient
      hospital-based smoking cessation interventions. METHODS: Electronic searches were
      conducted with two different search engines, and reference sections of articles
      located were also reviewed. The RE-AIM framework was used to organize the review
      around the issues of reach, efficacy, adoption, implementation, and maintenance
      of interventions. RESULTS: Thirty-one intervention articles were located, 20 of
      which included a comparison condition and were included in the review. Overall, a
      moderate number of studies (13/20) reported on reach, which was highly variable
      and limited (30-50% in most studies), while few reported on implementation
      (7/20). Longer term cessation results produced relative risk ratios of 0.9-2.3,
      with a median of 1.5. Increases in quit rates above the control condition ranged
      from -1 to 10% (median 4%) among general admission patients and from 7 to 36%
      (median 15%) among cardiac admission patients. Studies with a dedicated smoking
      cessation counselor and 3-5 months of relapse prevention had a significant impact
      on cessation rates. Study settings (adoption) were limited to university,
      Veterans affairs, and HMO hospitals. Maintenance at the individual level was
      variable and related to the presence of a relatively intensive initial
      intervention and a sustained relapse prevention intervention. CONCLUSIONS:
      Efficacious inpatient smoking programs have been developed and validated. The
      challenge now is to translate these interventions more widely into practice,
      given changing hospitalization patterns.

PMID- 11304100
TI  - Health care professionals may positively impact a smoker's willingness to quit
      smoking by direct interaction.

PMID- 11304102
TI  - Renal insufficiency as a predictor of cardiovascular outcomes and the impact of
      ramipril: the HOPE randomized trial.
AB  - BACKGROUND: The cardiovascular risk associated with early renal insufficiency is
      unknown. Clinicians are often reluctant to use angiotensin-converting enzyme
      inhibitors in patients with renal insufficiency. OBJECTIVE: To determine whether
      mild renal insufficiency increases cardiovascular risk and whether ramipril
      decreases that risk. DESIGN: Post hoc analysis. SETTING: The Heart Outcomes and
      Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational
      trial involving 267 study centers. PATIENTS: 980 patients with mild renal
      insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL])
      and 8307 patients with normal renal function (serum creatinine concentration <
      124 micromol/L [<1.4 mg/dL]) Patients with a baseline serum creatinine
      concentration greater than 200 micromol/L (2.3 mg/dL) were excluded.
      MEASUREMENTS: The primary outcome measure was incidence of cardiovascular death,
      myocardial infarction, or stroke. RESULTS: Cumulative incidence of the primary
      outcome was higher in patients with renal insufficiency than in those without
      (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration.
      Patients with renal insufficiency had a substantially increased risk for
      cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P <
      0.001 for both comparisons). The effect of renal insufficiency on the primary
      outcome (adjusted hazard ratio, 1.40 [95% CI, 1.16 to 1.69]) was independent of
      known cardiovascular risks and treatment. Ramipril reduced the incidence of the
      primary outcome in patients with and those without renal insufficiency (hazard
      ratio, 0.80 vs. 0.79; P > 0.2 for the difference). CONCLUSIONS: In patients who
      had preexisting vascular disease or diabetes combined with an additional
      cardiovascular risk factor, mild renal insufficiency significantly increased the
      risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk
      without increasing adverse effects.

PMID- 11304103
TI  - Impact of age on perioperative complications and length of stay in patients
      undergoing noncardiac surgery.
AB  - BACKGROUND: Major surgical procedures are performed with increasing frequency in
      elderly persons, but the impact of age on resource use and outcomes is uncertain.
      OBJECTIVE: To evaluate the influence of age on perioperative cardiac and
      noncardiac complications and length of stay in patients undergoing noncardiac
      surgery. DESIGN: Prospective cohort study. SETTING: Urban academic medical
      center. PATIENTS: Consecutive sample of 4315 patients 50 years of age or older
      who underwent nonemergent major noncardiac procedures. MEASUREMENTS: Major
      perioperative complications (cardiac and noncardiac), in-hospital mortality, and
      length of stay. RESULTS: Major perioperative complications occurred in 4.3% (44
      of 1015) of patients 59 years of age or younger, 5.7% (93 of 1646) of patients 60
      to 69 years of age, 9.6% (129 of 1341) of patients 70 to 79 years of age, and
      12.5% (39 of 313) of patients 80 years of age or older (P < 0.001). In-hospital
      mortality was significantly higher in patients 80 years of age or older than in
      those younger than 80 years of age (0.7% vs. 2.6%, respectively). Multivariate
      analyses indicated an increased odds ratio for perioperative complications or in
      hospital mortality in patients 70 to 79 years of age (1.8 [95% CI, 1.2 to 2.7])
      and those 80 years of age or older (OR, 2.1 [CI, 1.2 to 3.6]) compared with
      patients 50 to 59 years of age. Patients 80 years of age or older stayed an
      average of 1 day more in the hospital, after adjustment for other clinical data
      (P = 0.001). CONCLUSIONS: Elderly patients had a higher rate of major
      perioperative complications and mortality after noncardiac surgery and a longer
      length of stay, but even in patients 80 years of age or older, mortality was low.

PMID- 11304104
TI  - Treatment of patients with myocardial infarction who present with a paced rhythm.
AB  - BACKGROUND: A paced rhythm can mask the electrocardiographic features of an acute
      myocardial infarction, complicating timely recognition and treatment. OBJECTIVE:
      To evaluate characteristics, treatment, and outcomes among patients presenting
      with paced rhythms during myocardial infarction. DESIGN: Retrospective cohort
      study. SETTING: U.S. acute care hospitals. PATIENTS: 102 249 Medicare
      beneficiaries at least 65 years of age who were treated for acute myocardial
      infarction between 1994 and 1996. MEASUREMENTS: Provision of three treatments for
      acute myocardial infarction (emergent reperfusion, aspirin, and beta-blockers),
      death at 30 days, and long-term follow-up. RESULTS: 1954 patients (1.9%)
      presented with paced rhythms during myocardial infarction. These patients were
      older; were predominantly male; and had higher rates of congestive heart failure,
      diabetes, and previous infarction. They were significantly less likely to receive
      emergent reperfusion (relative risk [RR], 0.27 [95% CI, 0.22 to 0.33]), aspirin
      (RR at admission, 0.91 [CI, 0.88 to 0.94]; RR at discharge, 0.87 [CI, 0.83 to
      0.92]), and beta-blockers at admission (RR, 0.89 [CI, 0.82 to 0.96]). In
      addition, there was a trend toward decreased use of beta-blockers at discharge
      (RR, 0.91 [CI, 0.76 to 1.06]). Crude mortality rates were higher among patients
      with paced rhythms than among those without at 30 days (25.8% vs. 21.3%; P =
      0.001) and at 1 year (47.1% vs. 36.1%; P = 0.001). Among patients with paced
      rhythms, risk for death at 30 days decreased after adjustment for illness
      severity and decreased use of therapy (RR, 1.03 [CI, 0.93 to 1.14]). Patients
      with paced rhythms remained at additional risk for long-term mortality (hazard
      ratio, 1.12 [CI, 1.06 to 1.18]). CONCLUSIONS: Patients with paced rhythms were
      less likely than those without to receive treatment for acute myocardial
      infarction and had poorer short- and long-term outcomes. However, this mortality
      risk diminished after adjustment for treatment. This suggests that improved
      recognition and treatment of myocardial infarction may improve outcomes,
      particularly in the short term.

PMID- 11304105
TI  - Neocytolysis on descent from altitude: a newly recognized mechanism for the
      control of red cell mass.
AB  - BACKGROUND: Studies of space-flight anemia have uncovered a physiologic process,
      neocytolysis, by which young red blood cells are selectively hemolyzed, allowing
      rapid adaptation when red cell mass is excessive for a new environment.
      OBJECTIVES: 1) To confirm that neocytolysis occurs in another situation of acute
      plethora-when high-altitude dwellers with polycythemia descend to sea level; and
      2) to clarify the role of erythropoietin suppression. DESIGN: Prospective
      observational and interventional study. SETTING: Cerro de Pasco (4380 m) and Lima
      (sea level), Peru. PARTICIPANTS: Nine volunteers with polycythemia.
      INTERVENTIONS: Volunteers were transported to sea level; three received low-dose
      erythropoietin. MEASUREMENTS: Changes in red cell mass, hematocrit, hemoglobin
      concentration, reticulocyte count, ferritin level, serum erythropoietin, and
      enrichment of administered(13)C in heme. RESULTS: In six participants, red cell
      mass decreased by 7% to 10% within a few days of descent; this decrease was
      mirrored by a rapid increase in serum ferritin level. Reticulocyte production did
      not decrease, a finding that establishes a hemolytic mechanism.(13)C changes in
      circulating heme were consistent with hemolysis of young cells. Erythropoietin
      was suppressed, and administration of exogenous erythropoietin prevented the
      changes in red cell mass, serum ferritin level, and(13)C-heme. CONCLUSIONS:
      Neocytolysis and the role of erythropoietin are confirmed in persons with
      polycythemia who descend from high altitude. This may have implications that
      extend beyond space and altitude medicine to renal disease and other situations
      of erythropoietin suppression, hemolysis, and polycythemia.

PMID- 11304106
TI  - The CONSORT statement: revised recommendations for improving the quality of
      reports of parallel-group randomized trials.
AB  - To comprehend the results of a randomized, controlled trial (RCT), readers must
      understand its design, conduct, analysis, and interpretation. That goal can be
      achieved only through complete transparency from authors. Despite several decades
      of educational efforts, the reporting of RCTs needs improvement. Investigators
      and editors developed the original CONSORT (Con solidated S tandards o f R
      eporting T rials) statement to help authors improve reporting by using a
      checklist and flow diagram. The revised CONSORT statement presented in this paper
      incorporates new evidence and addresses some criticisms of the original
      statement. The checklist items pertain to the content of the Title, Abstract,
      Introduction, Methods, Results, and Discussion. The revised checklist includes 22
      items selected because empirical evidence indicates that not reporting the
      information is associated with biased estimates of treatment effect or because
      the information is essential to judge the reliability or relevance of the
      findings. We intended the flow diagram to depict the passage of participants
      through an RCT. The revised flow diagram depicts information from four stages of
      a trial (enrollment, intervention allocation, follow-up, and analysis). The
      diagram explicitly includes the number of participants, for each intervention
      group, that are included in the primary data analysis. Inclusion of these numbers
      allows the reader to judge whether the authors have performed an intention-to
      treat analysis. In sum, the CONSORT statement is intended to improve the
      reporting of an RCT, enabling readers to understand a trial's conduct and to
      assess the validity of its results.

PMID- 11304107
TI  - The revised CONSORT statement for reporting randomized trials: explanation and
      elaboration.
AB  - Overwhelming evidence now indicates that the quality of reporting of randomized,
      controlled trials (RCTs) is less than optimal. Recent methodologic analyses
      indicate that inadequate reporting and design are associated with biased
      estimates of treatment effects. Such systematic error is seriously damaging to
      RCTs, which boast the elimination of systematic error as their primary hallmark.
      Systematic error in RCTs reflects poor science, and poor science threatens proper
      ethical standards. A group of scientists and editors developed the CONSORT (Con
      solidated S tandards o f R eporting T rials) statement to improve the quality of
      reporting of RCTs. The statement consists of a checklist and flow diagram that
      authors can use for reporting an RCT. Many leading medical journals and major
      international editorial groups have adopted the CONSORT statement. The CONSORT
      statement facilitates critical appraisal and interpretation of RCTs by providing
      guidance to authors about how to improve the reporting of their trials. This
      explanatory and elaboration document is intended to enhance the use,
      understanding, and dissemination of the CONSORT statement. The meaning and
      rationale for each checklist item are presented. For most items, at least one
      published example of good reporting and, where possible, references to relevant
      empirical studies are provided. Several examples of flow diagrams are included.
      The CONSORT statement, this explanatory and elaboration document, and the
      associated Web site ( http://www.consort-statement.org ) should be helpful
      resources to improve reporting of randomized trials. Throughout the text, terms
      marked with an asterisk are defined at end of text.

PMID- 11304108
TI  - Rational use of new and existing disease-modifying agents in rheumatoid
      arthritis.
AB  - Because of radiographic evidence of progressive bone loss and the inability to
      eliminate synovial proliferation with methotrexate, it became apparent that
      therapy for rheumatoid arthritis needed further advancement. Methotrexate is not
      a remission-inducing drug and may have dose-limiting toxicity. In the past 2
      years, three new disease-modifying antirheumatic drugs (DMARDs) have been
      approved: leflunomide, etanercept, and infliximab. Each of these agents has
      demonstrated efficacy compared with placebo in randomized, controlled studies.
      Because methotrexate had a dominant therapeutic role, the new drugs were also
      studied in combination with it. Other established DMARDs, such as sulfasalazine
      and hydroxychloroquine, have also demonstrated efficacy when used together with
      methotrexate. The results of these combination studies clearly demonstrate that
      clinical responses can be meaningfully improved when new and existing DMARDs are
      added to methotrexate. Although toxicity remains a serious concern when powerful
      immune modulators and antimetabolites are used in combination, relatively few
      serious adverse events have been reported during 2-year treatment periods. It has
      also become apparent that combinations of new DMARDs and methotrexate virtually
      halt radiographic progression over 2 years. The new agents are expensive, but
      annual costs must be weighed against the personal and societal expense of joint
      arthroplasty, hospitalizations, disability, and diminished quality of life that
      accompanies poorly controlled rheumatoid arthritis. The ultimate value of
      combination DMARD therapy with methotrexate will be determined by long-term data
      on safety, efficacy, and effects on radiographic deterioration of bone.
      Additional long-term observational data on the incidence of joint arthroplasty
      and disability will help to place the issue of societal costs in a better
      perspective. This will allow the value of aggressive treatment to be established
      with certainty.

PMID- 11304109
TI  - The kidney in cardiovascular disease.

PMID- 11304110
TI  - Out of thin air: the evolving enigma of erythropoietin and neocytolysis.

PMID- 11304111
TI  - Treatment of heroin dependence.

PMID- 11304113
TI  - Tattoo-related brachial plexopathies with adjacent muscle atrophy.

PMID- 11304115
TI  - Correction: summary for patients on genes for hemochromatosis.

PMID- 11304118
TI  - Clinical librarianship: its value in medical care.

PMID- 11304119
TI  - In memoriam: James A. Miller (1915-2000).
AB  - Please also refer to the excellent obituaries written by Miriam Poirier in
      Carcinogenesis and by Allan Conney in Cancer Research.

PMID- 11304120
TI  - Allosteric behavior in cytochrome p450-dependent in vitro drug-drug interactions:
      a prospective based on conformational dynamics.

PMID- 11304121
TI  - Gibbs energy of formation of peroxynitrite.
AB  - A standard Gibbs energy of formation of 16.6 kcal mol(-)(1) has been reported for
      peroxynitrite [Merenyi, G., and Lind, J. (1998) Chem. Res. Toxicol. 11, 243-246].
      This value is based on the rate constants for the forward and backward rate
      constants of the equilibrium O2*- + NO* if ONOO(-). A rate constant of 0.017 s(
      )(1) for the backward rate constant was determined by observing the formation of
      C(NO(2))(3)(-) when peroxynitrite was mixed with C(NO(2))(4). However, a similar
      rate constant is also observed in the presence of NO(*), which indicates that
      formation of C(NO(2))(3)(-) is due to a process other than the reduction of
      C(NO(2))(4) by O2*-. Additionally, copper(II) nitrilotriacetate enhances the
      decay of ONOO(-) at pH 9.3, without reduction of copper(II). The preferred
      thermodynamic values are therefore as follows: Delta(f)H degrees (ONOO(-)) = -10
      +/- 2 kcal mol(-)(1), Delta(f)G degrees (ONOO(-)) = 14 +/- 3 kcal mol(-)(1), S
      degrees (ONOO(-)) = 31 eu, and E degrees '(ONOOH/NO(2)(*), H(2)O) = 1.6 V at pH 7
      [Koppenol, W. H., and Kissner, R. (1998) Chem. Res. Toxicol. 11, 87-90].

PMID- 11304122
TI  - DNA oxidation induced by cyclooxygenase-2.
AB  - The inducible form of cyclooxygenase, COX-2, has been shown to be overexpressed
      in various types of tumors, including colon and prostate cancer. Several studies
      indicate that COX-2 inhibition can be beneficial for the prevention of these
      types of cancer. Since COX-2 reactions involve production of reactive oxygen
      radicals that can potentially damage biological macromolecules, we explored the
      possibility that DNA and/or nucleosides can be oxidized during cyclooxygenase
      reactions. When DNA or nucleosides were incubated with COX-2 and arachidonic
      acid, a significant increase in the amount of 8-oxo-2'-deoxyguanosine was
      observed. This increase was enzyme-dependent and could be prevented by COX-2
      inhibitors as well as by antioxidants. These data indicate that peroxyl radicals
      or other oxidized species formed during conversion of arachidonic acid to
      prostaglandin G(2) might be responsible for the observed oxidation. These results
      suggest also that overexpression of COX-2 in inflammatory diseases places an
      additional burden on antioxidative defenses of the cell, which might contribute
      to DNA oxidation and the induction of mutations.

PMID- 11304123
TI  - Methylated trivalent arsenic species are genotoxic.
AB  - The reactivities of methyloxoarsine (MAs(III)) and iododimethylarsine
      (DMAs(III)), two methylated trivalent arsenicals, toward supercoiled phiX174 RFI
      DNA were assessed using a DNA nicking assay. The induction of DNA damage by these
      compounds in vitro in human peripheral lymphocytes was assessed using a single
      cell gel (SCG, "comet") assay. Both methylated trivalent arsenicals were able to
      nick and/or completely degrade phiX174 DNA in vitro in 2 h incubations at 37
      degrees C (pH 7.4) depending on concentration. MAs(III) was effective at nicking
      phiX174 DNA at 30 mM; however, at 150 microM DMAs(III), nicking could be
      observed. Exposure of phiX174 DNA to sodium arsenite (iAs(III); from 1 nM up to
      300 mM), sodium arsenate (from 1 microM to 1 M), and the pentavalent arsenicals,
      monomethylarsonic acid (from 1 microM to 3 M) and dimethylarsinic acid (from 0.1
      to 300 mM), did not nick or degrade phiX174 DNA under these conditions. In the
      SCG assay in human lymphocytes, methylated trivalent arsenicals were much more
      potent than any other arsenicals that were tested. On the basis of the slopes of
      the concentration-response curve for the tail moment in the SCG assay, MAs(III)
      and DMAs(III) were 77 and 386 times more potent than iAs(III), respectively.
      Because methylated trivalent arsenicals were the only arsenic compounds that were
      observed to damage naked DNA and required no exogenously added enzymatic or
      chemical activation systems, they are considered here to be direct-acting forms
      of arsenic that are genotoxic, though they are not, necessarily, the only
      genotoxic species of arsenic that could exist.

PMID- 11304124
TI  - Halothane-induced liver injury in outbred guinea pigs: role of
      trifluoroacetylated protein adducts in animal susceptibility.
AB  - Halothane causes a mild form of liver injury in guinea pigs that appears to model
      the hepatotoxicity seen in approximately 20% of patients treated with this drug.
      In previous studies, it was concluded that the increased susceptibility of some
      outbred guinea pigs to halothane-induced liver injury is not caused by their
      inherent ability to metabolize halothane to form toxic levels of
      trifluoroacetylated protein adducts in the liver. In this study, we reevaluated
      the role of trifluoroacetylated protein adducts in halothane-induced liver injury
      in guinea pigs. Male outbred Hartley guinea pigs were treated with halothane
      intraperitoneally. On the basis of serum alanine aminotransferase levels and
      liver histology, treated animals were designated as being susceptible, mildly
      susceptible, or resistant to halothane. Immunoblot studies with the use of anti
      trifluoroacetylated antibodies showed that susceptible guinea pigs for the most
      part had higher levels of trifluoroacetylated protein adducts in the liver 48 h
      after treatment with halothane than did less susceptible animals. In support of
      this finding, the level of trifluoroacetylated protein adducts detected
      immunochemically in the sera of treated guinea pigs correlated with sera levels
      of alanine aminotransferase activity. In addition, the levels of cytochrome P450
      2A-related protein but not those of other cytochrome P450 isoforms, measured by
      immunoblot analysis with isoform-specific antibodies, correlated with the amount
      of trifluoroacetylated protein adducts detected in the livers of guinea pigs 8 h
      after halothane administration. The results of this study indicate that the
      susceptibility of outbred guinea pigs to halothane-induced liver injury is
      related to an enhanced ability to metabolize halothane in the liver to form
      relatively high levels of trifluoroacetylated protein adducts. They also suggest
      that cytochrome P450 2A-related protein might have a major role in catalyzing the
      formation of trifluoroacetylated protein adducts in the liver of susceptible
      guinea pigs. Similar mechanisms may be important in humans.

PMID- 11304125
TI  - Identification of dimethylarsinous and monomethylarsonous acids in human urine of
      the arsenic-affected areas in West Bengal, India.
AB  - A speciation technique for arsenic has been developed using an anion-exchange
      high-performance liquid chromatography/inductively coupled argon plasma mass
      spectrometer (HPLC/ICP MS). Under optimized conditions, eight arsenic species
      [arsenocholine, arsenobetaine, dimethylarsinic acid (DMA(V)), dimethylarsinous
      acid (DMA(III)), monomethylarsonic acid (MMA(V)), monomethylarsonous acid
      (MMA(III)), arsenite (As(III)), and arsenate (As(V))] can be separated with
      isocratic elution within 10 min. The detection limit of arsenic compounds was
      0.14-0.33 microg/L. To validate the method, Standard Reference Material in freeze
      dried urine, SRM-2670, containing both normal and elevated levels of arsenic was
      analyzed. The method was applied to determine arsenic species in urine samples
      from three arsenic-affected districts of West Bengal, India. Both DMA(III) and
      MMA(III) were detected directly (i.e., without any prechemical treatment) for the
      first time in the urine of some humans exposed to inorganic arsenic through their
      drinking water. Of 428 subjects, MMA(III) was found in 48% and DMA(III) in 72%.
      Our results indicate the following. (1) Since MMA(III) and DMA(III) are more
      toxic than inorganic arsenic, it is essential to re-evaluate the hypothesis that
      methylation is the detoxification pathway for inorganic arsenic. (2) Since MMA(V)
      reductase with glutathione (GSH) is responsible for conversion of MMA(V) to
      MMA(III) in vivo, is DMA(V) reductase with GSH responsible for conversion of
      DMA(V) to DMA(III) in vivo? (3) Since DMA(III) forms iron-dependent reactive
      oxygen species (ROS) which causes DNA damage in vivo, DMA(III) may be responsible
      for arsenic carcinogenesis in human.

PMID- 11304126
TI  - Synthesis and characterization of nucleosides and oligonucleotides bearing
      adducts of butadiene epoxides on adenine n(6) and guanine n(2).
AB  - Butadiene is a major industrial chemical whose genotoxic effects are attributed
      to the reaction of its oxidized metabolites, butadiene monoepoxide (BDO) and
      butadiene diepoxide (BDO2), with DNA. Nucleosides and oligonucleotides containing
      regio- and stereochemically specific adducts of BDO and the BDO2-related
      compound, butene 3,4-diol 1,2-epoxide (BDE), on guanine [(2R)- and (2S)-N(2)-(1
      hydroxy-3-buten-2-yl) and (2R,3R)- and (2S,3S)-N(2)-(2,3,4-trihydroxybut-1-yl),
      respectively] and on adenine [(2R)- and (2S)-N(6)-(1-hydroxy-3-buten-2-yl) and
      (2R,3R)- and (2S,3S)-N(6)-(2,3,4-trihydroxybut-1-yl), respectively] have been
      prepared by nonbiomimetic routes. For guanine adducts, 2-fluoro-O(6)
      (trimethylsilylethyl)-2'-deoxyinosine was treated with (2R)- and (2S)-2-amino-3
      buten-1-ol to give the BDO adducts and with (2R,3R)- and (2S,3S)-1-amino-2,3,4
      butanetriol to produce the BDE adducts; the adducted oligonucleotides were
      prepared from 11-mer oligonucleotides containing the halopurine. Adenine adducts
      were prepared in a similar fashion using 6-chloropurine 2'-deoxyriboside as the
      reactive purine component.

PMID- 11304127
TI  - T cells ignore aniline, a prohapten, but respond to its reactive metabolites
      generated by phagocytes: possible implications for the pathogenesis of toxic oil
      syndrome.
AB  - The most basic arylamine, aniline, belongs to a class of compounds notorious for
      inducing allergic and autoimmune reactions. In 1981 in Spain, many people
      succumbed to toxic oil syndrome (TOS), a disease caused by ingestion of cooking
      oil contaminated with aniline. Indirect evidence points toward an immune
      pathogenesis of TOS driven by T lymphocytes, but it is unclear to which antigens
      these cells could react. Here, using the popliteal lymph node (PLN) assay in
      mice, we analyzed the sensitizing potential of aniline, its metabolites, and some
      of the aniline-coupled lipids detected in the contaminated cooking oil. Whereas
      aniline itself and its non-protein-reactive metabolites nitrobenzene, p
      aminophenol and N-acetyl-p-aminophenol, failed to elicit PLN responses, its
      reactive metabolites nitrosobenzene and N-hydroxylaniline did. The aniline
      coupled lipids, namely, linoleic anilide and linolenic anilide, and a mixture of
      fatty acid esters of 3-(N-phenylamino)-1,2-propanediol, all implicated in TOS,
      induced significant PLN responses, whereas the respective aniline-free lipids,
      linoleic acid, linolenic acid, and triolein, did not. Hence, the aniline moiety
      plays a crucial role in the immunogenicity of the aniline-coupled lipids of TOS.
      PLN responses to the reactive aniline metabolites and the one aniline-coupled
      lipid that was tested, linolenic anilide, were T-cell-dependent. Secondary PLN
      responses to nitrosobenzene were detectable not only after priming with
      nitrosobenzene but, in some experiments, also after priming with linolenic
      anilide. This suggests that the aniline moiety was cleaved from the aniline
      coupled lipid and metabolized to the intermediate nitrosobenzene that generated
      the prospective neoantigens. Consistent with this, in lymphocyte proliferation
      tests in vitro, T cells primed to nitrosobenzene reacted in anamnestic fashion to
      white bone marrow cells (WBMCs) pulsed with aniline. Hence, we propose that
      aniline is a prohapten that can be metabolized by WBMCs, which form neoantigens
      that are recognized by T cells. The possible significance of these findings for
      the pathogenesis of TOS is discussed.

PMID- 11304128
TI  - Structure-activity study on the quinone/quinone methide chemistry of flavonoids.
AB  - A structure-activity study on the quinone/quinone methide chemistry of a series
      of 3',4'-dihydroxyflavonoids was performed. Using the glutathione trapping method
      followed by HPLC, (1)H NMR, MALDI-TOF, and LC/MS analysis to identify the
      glutathionyl adducts, the chemical behavior of the quinones/quinone methides of
      the different flavonoids could be deduced. The nature and type of mono- and
      diglutathionyl adducts formed from quercetin, taxifolin, luteolin, fisetin, and
      3,3',4'-trihydroxyflavone show how several structural elements influence the
      quinone/quinone methide chemistry of flavonoids. In line with previous findings,
      glutathionyl adduct formation for quercetin occurs at positions C6 and C8 of the
      A ring, due to the involvement of quinone methide-type intermediates. Elimination
      of the possibilities for efficient quinone methide formation by (i) the absence
      of the C3-OH group (luteolin), (ii) the absence of the C2=C3 double bond
      (taxifolin), or (iii) the absence of the C5-OH group (3,3',4'-trihydroxyflavone)
      results in glutathionyl adduct formation at the B ring due to involvement of the
      o-quinone isomer of the oxidized flavonoid. The extent of di- versus
      monoglutathionyl adduct formation was shown to depend on the ease of oxidation of
      the monoadduct as compared to the parent flavonoid. Finally, unexpected results
      obtained with fisetin provide new insight into the quinone/quinone methide
      chemistry of flavonoids. The regioselectivity and nature of the quinone adducts
      that formed appear to be dependent on pH. At pH values above the pK(a) for
      quinone protonation, glutathionyl adduct formation proceeds at the A or B ring
      following expected quinone/quinone methide isomerization patterns. However,
      decreasing the pH below this pK(a) results in a competing pathway in which
      glutathionyl adduct formation occurs in the C ring of the flavonoid, which is
      preceded by protonation of the quinone and accompanied by H(2)O adduct formation,
      also in the C ring of the flavonoid. All together, the data presented in this
      study confirm that quinone/quinone methide chemistry can be far from
      straightforward, but the study provides significant new data revealing an
      important pH dependence for the chemical behavior of this important class of
      electrophiles.

PMID- 11304129
TI  - Inhibition of microsomal epoxide hydrolases by ureas, amides, and amines.
AB  - The microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism
      of xenobiotics such as polyaromatic toxicants. Additionally, polymorphism studies
      have underlined a potential role of this enzyme in relation to several diseases,
      such as emphysema, spontaneous abortion, and several forms of cancer. To provide
      new tools for studying the function of mEH, inhibition of this enzyme was
      investigated. Inhibition of recombinant rat and human mEH was achieved using
      primary ureas, amides, and amines. Several of these compounds are more potent
      than previously published inhibitors. Elaidamide, the most potent inhibitor that
      is obtained, has a K(i) of 70 nM for recombinant rat mEH. This compound interacts
      with the enzyme forming a noncovalent complex, and blocks substrate turnover
      through an apparent mix of competitive and noncompetitive inhibition kinetics.
      Furthermore, in insect cell cultures expressing rat mEH, elaidamide enhances the
      toxicity effects of epoxide-containing xenobiotics. These inhibitors could be
      valuable tools for investigating the physiological and toxicological roles of
      mEH.

PMID- 11304130
TI  - Cu(II)/H2O2-induced DNA damage is enhanced by packaging of DNA as a nucleosome.
AB  - Copper is a physiologically important, redox-active metal that may be involved in
      endogenous DNA damage and mutagenesis. To understand the factors that affect the
      location and quantity of copper-induced oxidative DNA damage in cells, we used
      the 5S rDNA nucleosome as a model to assess the effect of chromatin structure on
      DNA damage produced by Cu(II)/H2O2. Packaging of DNA into a nucleosome increased
      the extent of Cu(II)/H2O2-induced strand breaks by a factor of 2, while the
      extent of base lesions sensitive to Fpg and endo III glycosylases increased 8
      fold. We also observed that Cu(II)/H2O2 caused slightly more strand breaks than
      base lesions in isolated 5S rDNA (ratio of base lesions to strand breaks of
      approximately 0.6), while base lesions outnumbered strand breaks by a factor of 3
      4 when the DNA was incorporated into a nucleosome. Apart from several sites of
      enhanced or diminished DNA damage, there were no major changes in the sequence
      selectivity of Cu(II)/H2O2, and there was no apparent footprinting effect
      associated with nucleosome structure, such as that observed with the Fe(II)-EDTA
      complex. Possible mechanisms for explaining these observations include (1) an
      increase in Cu(II) concentration in the vicinity of nucleosomal DNA caused by
      binding of Cu to histone proteins or (2) increased reactivity or accessibility of
      nucleobases caused by DNA conformational changes associated with nucleosome
      structure. The enhancement of Cu(II)/H2O2-induced DNA damage in nucleosomes
      stands in contrast to the protective effect afforded DNA by proteins in chromatin
      against radiation-induced DNA damage.

PMID- 11304131
TI  - A Schiff base is a major DNA adduct of crotonaldehyde.
AB  - Previous studies have demonstrated that the reaction of crotonaldehyde with DNA
      produces Michael addition products, and these have been detected in human tissues
      as well as tissues of untreated laboratory animals. A second class of
      crotonaldehyde-DNA adducts releases 2-(2-hydroxypropyl)-4-hydroxy-6-methyl-1,3
      dioxane (paraldol, 12) upon hydrolysis, and these adducts are quantitatively more
      significant than the Michael addition adducts in vitro. In this study, we
      demonstrate that the major source of the paraldol-releasing DNA adducts of
      crotonaldehyde is a Schiff base. Reaction of crotonaldehyde with DNA, followed by
      treatment with NaBH(3)CN and enzyme hydrolysis, resulted in the formation of N(2)
      (3-hydroxybutyl)dG (10), identified by its UV, MS, and proton NMR. Reactions of
      crotonaldehyde or paraldol with dG demonstrated that the Schiff base precursor to
      N(2)-(3-hydroxybutyl)dG is N(2)-(3-hydroxybutylidene)dG (7), identified by UV, LC
      APCI-MS, and MS/MS. Four isomers of N(2)-(3-hydroxybutylidene)dG were observed.
      The (R)- and (S)-isomers were identified by reactions of chiral paraldol with dG;
      each existed as a pair of interconverting (E)- and (Z)-isomers. These data
      indicate that the structure of the major Schiff base DNA adduct in crotonaldehyde
      treated DNA is N(2)-(3-hydroxybutylidene)dG (7). This adduct is unstable at the
      nucleoside level and accounts for more than 90% of the paraldol released from
      crotonaldehyde-treated DNA. However, the adduct is stable in DNA and therefore is
      a likely companion to the Michael addition adducts in human DNA.

PMID- 11304132
TI  - Defining mechanisms of toxicity for linoleic acid monoepoxides and diols in Sf-21
      cells.
AB  - Linoleic acid monoepoxides have been correlated with many pathological
      conditions. Studies using insect cells derived from Spodoptera frugiperda (Sf-21
      cells) have suggested that conversion of the epoxides to the diols is required
      for toxicity. However, more recent studies using rabbit renal proximal tubules
      have suggested that linoleic acid monoepoxides are direct mitochondrial toxins.
      To better understand these discrepancies, we compared the toxicity of these
      linoleic acid metabolites in Sf-21 cells using mitochondrial respiration as an
      end point. Linoleic acid (100 microM) and 12,13-epoxy-9-octadecenoic acid (12,13
      EOA, 100 microM) increased the rate of oligomycin-insensitive respiration by
      approximately 3.5- and 3-fold, respectively, decreased the rate of oligomycin
      sensitive respiration by approximately 52 and 68%, respectively, and had no
      effect on the integrity of the electron transport chain. These effects were
      concentration-dependent, occurred within 1 min, and recovered to basal levels
      within 45 min. 12,13-Dihydroxy-9-octadecenoic acid (12,13-DHOA, 100 microM) had
      no effect on oligomycin-insensitive respiration but decreased the rate of
      oligomycin-sensitive respiration and uncoupled respiration in a concentration
      dependent manner. Approximately 79 and 68% of oligomycin-sensitive respiration
      and uncoupled respiration was inhibited by 12,13-DHOA (100 microM), respectively.
      These effects occurred within 1 min and were not reversible in 6 h. Effects
      similar to those induced by 12,13-DHOA (100 microM) were observed using 12,13-EOA
      (100 microM) in Sf-21 cells expressing human soluble epoxide hydrolase. These
      data suggest that in this Sf-21 model linoleic acid and linoleic monoepoxides
      have transient uncoupling effects, whereas the primary mechanism of toxicity for
      linoleic acid diols in this model is inhibition of the electron transport chain.

PMID- 11304133
TI  - Analysis of peroxynitrite reactions with guanine, xanthine, and adenine
      nucleosides by high-pressure liquid chromatography with electrochemical
      detection: C8-nitration and -oxidation.
AB  - Peroxynitrite, the reaction product of nitric oxide and superoxide anion, and a
      powerful oxidant, was found to nitrate as well as oxidize adenine, guanine, and
      xanthine nucleosides. A highly sensitive reverse-phase HPLC method with a dual
      mode electrochemical detector, which reduces the nitro product at the first
      electrode and detects the reduced product by oxidation at the second electrode,
      was applied to detect femtomole levels of 8-nitroguanine and 8-nitroxanthine.
      This method was used to separate and identify the products of nitration and
      oxidation from the reactions of nucleosides with peroxynitrite. Peroxynitrite
      nitrates deoxyguanosine at neutral pH to give the very unstable 8
      nitrodeoxyguanosine, in addition to 8-nitroguanine. 8-Nitrodeoxyguanosine, with a
      half-life of approximately 10 min at room temperature and </=3 min at 37 degrees
      C, hydrolyzes at pH 7 to 8-nitroguanine. A decrease in the reaction pH resulted
      in a decrease in the level of C8-nitration. Peroxynitrite also oxidizes
      deoxyguanosine in a pH-dependent manner, to give 8-oxodeoxyguanosine with a
      maximum yield (0.5-0.7%) at pH 5. Guanosine and xanthosine exhibit reactivity
      similar to that of deoxyguanosine toward peroxynitrite at neutral pH, producing
      only the corresponding 8-nitronucleosides as well as 8-nitroguanine and 8
      nitroxanthine, respectively. 8-Nitroguanosine at pH 7, with a half-life of
      several weeks at 5 degrees C and 5 h at 37 degrees C, was much more stable than 8
      nitrodeoxyguanosine. C8-nitration was confirmed by dithionite reduction to the
      corresponding amino nucleosides, which cochromatographed with synthesized 8-amino
      nucleoside standards. In contrast to guanine nucleosides, adenine nucleosides
      undergo peroxynitrite-mediated C8 oxidation even at neutral pH to give the
      corresponding 8-oxoadenine nucleosides in approximately 0.3% yield. Adenine
      nitration, though minor compared to C8-oxidation, appears to occur at both C2 and
      C8 positions of the adenine ring. Lowering the reaction pH from 7 to 5 results in
      2.4- and 2.2-fold increases in the yields of 8-oxo-dA and 8-oxo-Ado,
      respectively, but the level of nitration is not altered.

PMID- 11304134
TI  - Reaction of trichloroethylene and trichloroethylene oxide with cytochrome P450
      enzymes: inactivation and sites of modification.
AB  - Trichloroethylene (TCE) has been shown to be toxic to experimental animals and
      humans. TCE oxide is a reactive electrophile formed during TCE oxidation and
      rearranges to acylating intermediates [Cai, H., and Guengerich, F. P. (1999) J.
      Am. Chem. Soc. 121, 11656-11663], which may be related to the toxicity. Mice
      treated with TCE have been reported to contain N(6)-dichloroacetylLys residues in
      P450 2E1, as detected by immunochemical methods. TCE can be oxidized by both P450
      2E1 and (rat) 2B1. In this work, direct reaction of TCE oxide with either human
      P450 2E1, P450 2B1, or NADPH-P450 reductase was shown to lead to enzyme
      inactivation, and no recovery of the activity of either enzyme occurred,
      consistent with the view of inactivation reactions with Lys groups and not
      hydroxyls or Cys. Furthermore, Lys adducts were detected in the reaction of TCE
      oxide with both P450 2E1 and NADPH-P450 reductase, with a larger amount of N(6)
      formylLys observed compared to N(6)-dichloroacetylLys in both cases. Inactivation
      of P450 2E1 during NADPH-dependent TCE oxidation was not observed, compared to
      control experiments. However, inactivation of P450 2B1 during NADPH-dependent TCE
      oxidation was detected. Matrix-assisted laser desorption ionization time-of
      flight mass spectrometry of tryptic peptides indicated that the direct reaction
      of TCE oxide with human P450 2E1 resulted in the modification of peptides
      containing Lys87 (AVKEALLDYK), Lys251 (VKEHHQSLDPNCPR), and Lys487 (YKLCVIPR),
      with either a formyl or dichloroacetyl group attached. Lys87 and Lys487 of human
      P450 2E1 appear to be modified during the oxidation of TCE, using the same
      approach. The results are considered in the context of comparison of species and
      P450s.

PMID- 11304137
TI  - Synthesis of nido-[1-OMe-2,3-(Cp*Ru)2[mu-P(OMe)2]B3H5]: methoxy transfer from
      phosphorus to boron and cluster core rearrangement.

PMID- 11304136
TI  - De novo nucleases based on HTH and EF-hand chimeras.

PMID- 11304138
TI  - Titanium eta1-pyrrolyl complexes: electronic and structural characteristics
      imposed by the N,N-di(pyrrolyl-alpha-methyl)-N-methylamine (dpma) ligand.

PMID- 11304139
TI  - Methylcyclopentadienyl-substituted tungsten(IV) sulfido cluster [(eta5
      Cp')3W3S4]+ and its heterobimetallic derivative [(eta5-Cp')3W3S4Ni(PPh3)]+ .
AB  - The aqueous cluster salt [(H2O)9W3S4][pts]4.9H2O (pts = p-toluenesulfonate) was
      converted to the methylcyclopentadienyl (Cp') substituted cluster [(eta5
      Cp')3W3S4][pts] ([1][pts]) from which the cubane-like cluster [(eta5
      Cp')3W3S4Ni(PPh3)][pts] ([2][pts]) was obtained by reaction with Ni(cod)2 and
      PPh3. [2][pts] was characterized by X-ray crystal structure analysis.

PMID- 11304140
TI  - An experimental and theoretical investigation of the carbon dioxide insertion
      process into the tungsten-nitrogen bond of an anionic W(0) complex.
AB  - The pyridine bound 2-aminopyridine (2APH) derivative of tungsten pentacarbonyl
      has been prepared from photogenerated W(CO)5THF and 2APH. Deprotonation of the
      distal amine group by sodium hydride has provided two complexes,
      [Na][W(CO)5(2AP)] and [Na]2[W(CO)4(2AP)]2. Both complexes have been characterized
      by X-ray crystallography with the monomeric derivative being crystallized as its
      [Na2(18-crown-6)][W(CO)5(2AP)]2 salt which exhibits strong Na+...-NH
      interactions. Photolysis of W(CO)6 in the presence of excess 2-aminopyridine in
      THF has led to an efficient synthesis of the chelated neutral derivative,
      W(CO)4(2APH).2APH, where the extra equivalent of 2APH is hydrogen bonded to its
      bound counterpart. The 2-aminopyridine molecule of solvation was almost
      quantitatively removed via aqueous washings. Deprotonation of W(CO)4(2APH) with
      NaH afforded the amidopyridine derivative which was shown to rapidly undergo
      reaction with CO2 to yield the chelated carbamate complex, W(CO)4(OC(O)2AP)-.
      Nevertheless, because of the presence of small quantities of free 2-aminopyridine
      during the reactions with CO2, we have not been able to conclusively rule out
      participation by a ligand substitution process involving NC5H4NHCOOH. Ab initio
      computations were found to substantiate many of these experimental observations.
      That is, in the monodentate bound W(CO)5(2APH) derivative, binding through the
      pyridine nitrogen atom is favored by about 29 kJ/mol over the amine nitrogen
      atom, whereas the opposite site for binding is preferred for the deprotonated
      amido analogue, W(CO)5(2AP)-. Furthermore, both forms of W(CO)5(2AP)- were found
      to be more stable than the chelated tungsten tetracarbonyl anion plus CO. On the
      other hand, CO2 insertion into the W(CO)4(2AP)- anion to provide the chelated
      carbamate, W(CO)4(OC(O)2AP)-, was thermodynamically favored by >110 kJ/mol.
      Finally, both experimental and theoretical studies were inconclusive with regard
      to identifying reaction intermediates during the CO2 insertion pathway which
      involve prior interactions of CO2 at the amido nitrogen center.

PMID- 11304141
TI  - About the Keggin isomers: crystal structure of [N(C4H9)4]-gamma-[SiMo2W10O40]n-
      (n= 4 or 6).
AB  - The tetrabutylammonium gamma-dodecatungstosilicate has been crystallized in a 6/1
      acetonitrile/water solvent. An X-ray single-crystal analysis was carried out on
      [N(C4H9)4]4-gamma-[SiW12O40] which crystallizes in the orthorhombic system, space
      group P2(1)2(1)2(1), with a = 19.0881(3) A, b = 21.4435(3) A, c = 26.0799(1) A, V
      = 10674.9(2) A3, Z = 4, and rho(calcd) = 2.392 g/cm3. The idealized C2v
      arrangement of the anion results from the rotation of 60 degrees of two trigonal
      [W3O13] groups in the Keggin anion. Taking as reference the geometrical
      characteristics of the Keggin anion, it appears that the bond lengths and bonds
      angles within the four [W3O13] groups are not significantly modified while the mu
      oxo junctions between the two rotated groups and those between the two unrotated
      groups involve more acute and opened W-O-W angles, respectively. The syntheses
      and 183W NMR characterizations of the mixed gamma-[SiW10Mo2O40]n- compounds
      corresponding to the oxidized (Mo(VI); n = 4) and to the two electron-reduced
      (Mo(V); n = 6) anions are reported. Structural analysis by 183W NMR has proved
      unambiguously that the C2v structure of the gamma-[SiW10O36]8- subunit is
      retained in both the compounds. The electronic behavior of the series gamma
      [SiW10M2E2O36]6- (M = Mo or W; E = O or S) is examined, compared and related to
      183W NMR data.

PMID- 11304142
TI  - Chemistry of re with N,N'-bis(2-pyridylmethyl)ethylenediamine (H2pmen):
      hydrolysis, dehydrogenation, and ternary complexes.
AB  - A number of Re complexes with N,N'-bis(2-pyridylmethyl)ethylenediamine (H2pmen)
      have been made from [NH4][ReO4]. [ReOCl2(H2pmen)]Cl, [ReOCl(Hpmen)][ReO4], and
      [ReO2(H2pmen)][ReO4] are related by hydrolysis/HCl substitution.
      [ReOCl(Hpmen)][ReO4] was structurally characterized and found to contain a water
      stable amido-Re bond. Dehydrogenation of the N-donor ligand from each amine to
      imine with concomitant two-electron reduction of the Re center occurs readily in
      these systems. With suitable 3-hydroxy-4-pyrones, ternary complexes such as
      [ReIIICl(ma)(C14H14N4)][ReO4].CH3OH, 5, were made from [NH4][ReO4], H2pmen.4HCl
      and pyrones in one-pot syntheses. 5, a seven-coordinate ReIII complex, was
      structurally characterized.

PMID- 11304143
TI  - Dialkylaluminum hydrazides derived from free hydrazine N2H4. Molecular Structures
      of [(MeC)2AlN2H3]2 and [(MeC)2Al]4(N2H2)2.
AB  - The reaction of di(tert-butyl)aluminum hydride with hydrazine N2H4 afforded the
      hydrazide (Me3C)2AlN2H3, 1, by the release of elemental hydrogen. Compound 1 is a
      dimer in solution and in the solid state and possesses a six-membered Al2N4
      heterocycle in a twist conformation with two intact N-N bonds. Further reaction
      of 1 with an excess of HAl(CMe3)2 yielded the tricyclic aluminum and nitrogen
      rich Al4N4 compound [(Me3C)2AlN2H2]2[Al(CMe3)2]2, 2, in which each N-N bond of a
      central six-membered Al2N4 ring similar to that of 1 is side-on-coordinated to an
      Al(CMe3)2 group. The structure of 2 may be interpreted as a dimer of the
      dialuminum hydrazide (Me3C)2Al-NH-NH-Al(CMe3)2.

PMID- 11304144
TI  - Polar compounds constructed with the [Cr2O7]2- anion.
AB  - Crystalline KTiOPO4 (KTP), an inorganic nonlinear optical material with a
      waveguide figure-of-merit that is twice that of other mixed-metal oxides,
      contains helical chains of TiO(4/2)O(2/2) octahedra in which a long, short Ti-O
      bond motif results in a net c-directed polarization. The alternating long and
      short Ti-O bonds that occur along these chains are the major contributors to the
      large nonlinear optic and electrooptic coefficients. Analogous chains have been
      constructed using dichromate [Cr2O7]2- anions and [M(py)4]2+ (M = Cu, Zn)
      cations; these new transition metal oxides crystallize in the same space group as
      KTP. Crystal data for Cu(py)4Cr2O7: orthorhombic, space group Pna2(1) (No. 33),
      with a = 15.941(7) A, b = 16.324(3) A, c = 8.857(2) A, and Z = 4; for
      Zn(py)4Cr2O7, orthorhombic, space group Pna2(1) (No. 33), with a = 16.503(1) A, b
      = 16.005(1) A, c = 8.8130(5) A, and Z = 4; for Cd(py)4Cr2O7, monoclinic, space
      group C2/c (No. 15), with a = 14.8034(9) A, b = 11.1847(7) A, c = 15.788(1) A,
      beta = 110.023(1) degrees, and Z = 4.

PMID- 11304145
TI  - Acid-base and spectroelectrochemical properties of doubly N-confused porphyrins.
AB  - The cis-doubly N-confused porphyrin, H2N2CP, containing two adjacent confused
      pyrrole rings has been investigated from the point of view of its acid-base and
      electrochemical behavior in dichloromethane. This novel porphyrin isomer can form
      two metal-carbon bonds in the central core, stabilizing metal ions in unusually
      high oxidation states. Furthermore, the two outside N-pyrrole atoms remain
      available for acid-base and specific solvent interactions. Protonation of the
      pyrrole N atoms proceeds according to two successive steps, while only a single
      deprotonation step has been observed in the presence of bases. Similarly, in the
      case of the silver and copper complexes the protonation and deprotonation of the
      outer pyrrole rings have been detected, confirming the structure of the metalated
      species as M(III)-HN2CP. The electrochemical reduction of the metal ions (III/II
      redox process) and oxidation of the macrocycle ring have been detected
      respectively at -0.9 and 1.4 V based on spectroelectrochemical measurements in
      conjunction with the acid/base equilibrium studies. Additional waves observed
      around -0.5 and 1.3 V have been assigned to redox processes involving water
      molecules associated with the doubly N-confused porphyrins.

PMID- 11304146
TI  - Covalent titanium aryldioxy one-, two-, and three-dimensional networks and their
      examination as Ziegler-Natta catalysts.
AB  - Treatment of ((i)PrO)4Ti with 2,7-dihydroxynaphthalene at 100 degrees C afforded
      the one-dimensional ladder [cis-Ti(mu(2,7)-OC10H6O)2py2]n (1: C30H22N2O4Ti,
      orthorhombic, P2(1)2(1)2(1), a = 9.866(2) A, b = 15.962(3) A, c = 16.223(3) A, Z
      = 4), in pyridine, and the stacked ladder, two-dimensional [Ti(mu(2,7)
      OC10H6O)2(4-picoline)2.(4-picoline)(0.5)]n (2: C70H59N5O8Ti2, triclinic, P1, a =
      10.814(2) A, b = 16.785(3) A, c = 18.020(4) A, alpha = 93.88(3) degrees, beta =
      107.31(3) degrees, gamma = 108.77(3) degrees, Z = 2), in 4-picoline. A disruption
      of intramolecular edge-to-face and intermolecular face-to-face pi-stacking
      interactions in 1 by the Me group of the 4-picoline causes the structural change
      to 2. These derivatives and related two- and three-dimensional covalent metal
      organic networks (CMON) were assayed for ethylene and propylene polymerization
      activity via the addition of methylaluminoxane. CMON are mediocre Ziegler-Natta
      catalysts that generate polydisperse, linear polyethylene and atactic
      polypropylene. The data are best accommodated by viewing the degradation of CMON
      into numerous active sites of differing activity.

PMID- 11304147
TI  - Synthesis of TiRru2 heterobimetallic and TiRuM (M = Rh, Rr, Pd, Pt)
      heterotrimetallic sulfido clusters from a hydrosulfido-bridged titanium-ruthenium
      complex.
AB  - Treatment of the hydrosulfido-bridged titanium-ruthenium heterobimetallic complex
      [Cp2Ti(mu2-SH)2RuCl(eta5-C5Me5)] (1; Cp = eta5-C5H5) with an excess of
      triethylamine followed by addition of [RuCl2(PPh3)3] and [[(cod)M]2(mu2-Cl)2] (M
      = Rh, Ir; cod = 1,5-cyclooctadiene) led to the formation of the TiRu2 and TiRuM
      mixed-metal sulfido clusters [(CpTi)[(eta5-C5Me5)Ru][Ru(PPh3)2](mu3-S)2(mu2-Cl)2]
      (3) and [(CpTi)[(eta5-C5Me5)Ru][M(cod)](mu3-S)2(mu2-Cl)] (M = Rh (4a), Ir (4b)),
      respectively. On the other hand, the reactions of 1 with [M(PPh3)4] (M = Pd, Pt)
      afforded the TiRuM trinuclear clusters [(CpTiCl)[(eta5-C5Me5)Ru][M(PPh3)2](mu3
      S)(mu2-S)(mu2-H)] (M = Pd (5a), Pt (5b)) with an unprecedented M3(mu3-S)(mu2-S)
      core. The detailed structures of these triangular clusters 3-5 have been
      determined by X-ray crystallography. Crystal data: 3, triclinic, P1, a =
      12.448(4) A, b = 12.773(4) A, c = 17.270(4) A, alpha = 100.16(2) degrees, beta =
      99.93(2) degrees, gamma = 114.11(3) degrees, V = 2373(1) A(3), Z = 2; 4a,
      triclinic, P1, a = 7.714(2) A, b = 11.598(3) A, c = 14.802(4) A, alpha = 80.46(2)
      degrees, beta = 82.53(2) degrees, gamma = 71.47(2) degrees, V = 1234.0(6) A3, Z =
      2; 4b, triclinic, P1, a = 7.729(1) A, b = 11.577(2) A, c = 14.766(3) A, alpha =
      80.14(1) degrees, beta = 82.71(1) degrees, gamma = 71.55(1) degrees, V =
      1231.1(4) A3, Z = 2; 5a, monoclinic, P2(1)/c, a = 11.259(4) A, b = 16.438(4) A, c
      = 26.092(5) A, beta = 102.23(3) degrees, V = 4719(2) A(3), Z = 4; 5b, monoclinic,
      P2(1)/n, a = 11.369(2) A, b = 16.207(3) A, c = 26.116(2) A, beta = 102.29(1)
      degrees, V = 4701(1) A3, Z = 4.

PMID- 11304148
TI  - Silver as an exopolyhedral auxiliary to the rhenacarborane anion [Re(CO)3(eta5
      7,8-C2B9H11)]-.
AB  - The rhenacarborane salt Cs[Re(CO)3(eta5-7,8-C2B9H11)] (1) has been used to
      synthesize the tetranuclear metal complex [[ReAg(mu-10-H-eta5-7,8
      C2B9H10)(CO)3]2[mu-Ph2P(CH2)2PPh2]] (3) where two [ReAg(mu-10-H-eta5-7,8
      C2B9H10)(CO)3] fragments have been shown by X-ray crystallography to be bridged
      by a single 1,2-bis(diphenylphosphino)ethane ligand. Reaction of 1 with Ag[BF4]
      in the presence of the ligands bis- or tris(pyrazol-1-yl)methane yields the
      complexes [ReAg(mu-10-H-eta5-7,8-C2B9H10)(CO)3[kappa2-CH2(C3H3N2-1)2]] (4) or
      [[ReAg(mu-10-H-eta5-7,8-C2B9H10)(CO)3]2[mu-kappa1,kappa2-CH(C3H3N2-1)3]] (5),
      respectively. From X-ray studies, the former comprises a Re-Ag bond bridged by
      the carborane cage and with the bis(pyrazol-1-yl)methane coordinating the
      silver(I) center in an asymmetric kappa(2) mode. Complex 5 was unexpectedly found
      to contain a tris(pyrazol-1-yl)methane bridging two [ReAg(mu-10-H-eta5-7,8
      C2B9H10)(CO)3] fragments in a kappa1,kappa2 manner. Treatment of 1 with Ag[BF4]
      in the presence of 2,2'-dipyridyl and 2,2':6',2' '-terpyridyl yields [ReAg(mu-10
      H-eta5-7,8-C2B9H10)(CO)3[kappa2-(C5H4N-2)(2)]] (6) and [ReAg(mu-10-H-eta5-7,8
      C2B9H10)(CO)3[kappa3-C5H3N(C5H4N-2)2-2,6]] (7). The X-ray structure determination
      of 7 revealed an unusual pentacoordinated silver(I) center, asymmetrically
      ligated by a kappa3-2,2':6',2' '-terpyridyl molecule. The same synthetic
      procedure using N,N,N',N'-tetramethylethylenediamine gave a tetranuclear metal
      complex [[ReAg(mu-10-H-eta5-7,8-C2B9H10)(CO)3]2[mu-Me2N(CH2)2NMe2]2] (8) which is
      believed, in the solid state, to be bridged between the silver atoms by two of
      the diamine molecules. The salt 1 with Ag[BF4] in the absence of any added ligand
      gave the tetrameric cluster [ReAg[mu-5,6,10-(H)3-eta5-7,8-C2B9H8](CO)3]4 (9)
      where, in the solid state, four [ReAg(mu-10-H-eta5-7,8-C2B9H10)(CO)3] units are
      held together by long interunit B-H right harpoon-up Ag bonds.

PMID- 11304149
TI  - Mononuclear (Pd, Pt), heterodinuclear (PdAg, PtAg), and tetranuclear (Pd2Ag2,
      Pt2Ag2) 1,1-ethylenedithiolato complexes.
AB  - lp;&-5q;1 The reactions of [Tl2[S2C=C[C(O)Me]2]]n with [MCl2L2] (1:1) or with
      [MCl2(NCPh)2] and PPh3 (1:1:2) give complexes [M[eta2-S2C=C[C(O)Me]2]L2] [M = Pt,
      L2 = 1,5-cyclooctadiene (cod) (1); L2 = bpy, M = Pd (2a), Pt (2b), L = PPh3, M =
      Pd (3a), Pt (3b)] whereas with MCl2 and QCl (2:1:2) anionic derivatives Q2[M[eta2
      S2C=C[C(O)Me]2]2] [M = Pd, Q = NMe4 (4a), Ph3P=N=PPh3 (PPN) (4a'), M = Pt, Q =
      NMe4 (4b)] are produced. Complexes 1 and 3 react with AgClO4 (1:1) to give
      tetranuclear complexes [[ML2]2Ag2[mu2,eta2-(S,S')-[S2C=C[C(O)Me]2]2]](ClO4)2 [L =
      PPh3, M = Pd (5a), Pt (5b), L2 = cod, M = Pt (5b')], while the reactions of 3
      with AgClO4 and PPh3 (1:1:2) give dinuclear [[M(PPh3)2][Ag(PPh3)2][mu2,eta2
      (S,S')-S2C=C[C(O)Me]2]]]ClO4 [M = Pd (6a), Pt (6b)]. The crystal structures of
      3a, 3b, 4a, and two crystal forms of 5b have been determined. The two crystal
      forms of 5b display two [Pt(PPh3)2][mu2,eta2-(S,S')-[S2C=C[C(O)Me]2]2] moieties
      bridging two Ag(I) centers.

PMID- 11304150
TI  - Electron-transfer salts of 1,2,3,4,5-pentamethylferrocene, Fe(II)(C5Me5)(C5H5).
      Structure and magnetic properties of two 1:1 and two 2:3 Fe(C5Me5)(C5H5) electron
      transfer salts of tetracyanoethylene.
AB  - The reaction of Fe(II)(C5Me5)(C5H5), FeCpCp, with percyano acceptors, A [A =
      C4(CN)6 (hexacyanobutadiene), TCNQF4 (perfluoro-7,7,8,8-tetracyano-p
      quinodimethane), and DDQ (2,3-dichloro-5,6-dicyanobenzoquinone)], results in
      formation of 1:1 charge-transfer salts of [Fe(III)CpCp]*]*+[A]*- composition.
      With A = TCNQ (7,7,8,8-tetracyano-p-quinodimethane) a 1:2 electron-transfer salt
      with FeCpCp forms. With A = TCNE (tetracyanoethylene) a pair of 1:1 salts as well
      as a pair of 2:3 salts of [FeCpCp]2[TCNE]3.S (S = CH2Cl2, THF) have been isolated
      and characterized by single-crystal X-ray diffraction. [FeCpCp][TCNE] consists of
      parallel 1-D.D(*+)A(*-)D(*+)A(*-)D(*+)A(*-). chains, while [FeCpCp][TCNE].MeCN
      has a herringbone array of D(*+)A2(2-)D(*+) dimers separated by solvent
      molecules. Although each [TCNE](-) is disordered, the diamagnetic [TCNE]2(2-)
      dimer is structurally different from those observed earlier with an intradimer
      separation of 2.79 A. The [TCNE](-) in the 2:3 [FeCpCp]2[TCNE]3.S exists as an
      eclipsed diamagnetic [TCNE]2(2-) dimer with an intradimer ethylene C.C separation
      of 2.833 and 2.903 A for the CH2Cl2- and THF-containing materials, respectively.
      The bond distances and angles for all the cations are essentially equivalent, and
      the distances are essentially equivalent to those previously reported for
      [FeCp2](*+) and [FeCp2](*+) cations. The average Fe-C5H5-ring and Fe-C5Me5-ring
      centroid distances are 1.71 and 1.69 A, respectively, which are 0.05 A longer
      than reported for Fe(II)CpCp. The one-electron reduction potential for Fe(II)CpCp
      is 0.11 V (vs SCE). The 5 K EPR of [FeCpCp](*+)[BF4](-) exhibits an axially
      symmetric powder pattern with g(parallel) = 4.36 and g(perpendicular) = 1.24, and
      the EPR parameters are essentially identical to those reported for ferrocenium
      and decamethylferrocenium. The high-temperature magnetic susceptibility for
      polycrystalline samples of these complexes can be fit by the Curie-Weiss law, chi
      = C/(T - theta), with low theta values and mu(eff) values from 2.08 to 3.43
      mu(B), suggesting that the polycrystalline samples measured had varying degrees
      of orientation. [FeCpCp][TCNE] exhibits the highest effective moment of 3.43
      mu(B)/Fe and weak ferromagnetic coupling, as evidenced from the theta of 3.3 K;
      however, unexpectedly, it does not magnetically order above 2 K. The formation of
      the four phases comprising FeCpCp and TCNE emphasizes the diversity of materials
      that may form and the present inability to predict neither solid-state
      compositions nor structure types.

PMID- 11304151
TI  - [Fe(Phen)(CN)4]-: a versatile building block for the design of heterometallic
      systems. Crystal structures and magnetic properties of PPh4[Fe(Phen)(CN)4]*2H2O
      and [[Fe(Phen)(CN)4]2M(H2O)2]*4H2O [Phen = 1,10-phenanthroline; M = Mn(II) and
      Zn(II)].
AB  - The mononuclear PPh4[Fe(phen)(CN)4]*2H2O (1) complex and the cyanide-bridged
      bimetallic [[Fe(phen)(CN)4]2M(H2O)2]*4H2O compounds [M = Mn(II) (2) and Zn(II)
      (3); phen = 1,10-phenanthroline; PPh4 = tetraphenylphosphonium cation] have been
      synthesized and structurally and magnetically characterized. Complex 1
      crystallizes in the monoclinic system, space group P2(1)/c, with a = 9.364(4) A,
      b = 27.472(5) A, c = 14.301(3) A, beta = 97.68(2) degrees, and Z = 4. Complexes 2
      and 3 are isostructural and they crystallize in the monoclinic system, space
      group P2(1)/n, with a = 7.5292(4) A, b = 15.6000(10) A, c = 15.4081(9) A, beta =
      93.552(2) degrees, and Z = 2 for 2 and a = 7.440(1) A, b = 15.569(3) A, c =
      15.344(6) A, beta = 93.63(2) degrees, and Z = 2 for 3. The structure of complex 1
      is made up of mononuclear [Fe(phen)(CN)4]- anions, tetraphenyphosphonium cations,
      and water molecules of crystallization. The iron(III) is hexacoordinate with two
      nitrogen atoms of a chelating phen (2.018(6) and 2.021(6) A for Fe-N) and four
      carbon atoms of four terminal cyanide groups (Fe-C bond lengths varying in the
      range 1.906(8)-1.95(1) A) building a distorted octahedron around the metal atom.
      The structure of complexes 2 and 3 consists of neutral double zigzag chains of
      formula [[Fe(phen)(CN)4]2M(H2O)2] and crystallization water molecules. The
      [Fe(phen)(CN)4]- entity of 1 is present in 2 and 3 acting as a bridging ligand
      toward M(H2O)2 units [M = Mn(II) (2) and Zn(II) (3)] through two cyanide groups
      in cis positions, the other two cyanide remaining terminal. Two water molecules
      in trans positions and four cyanide-nitrogen atoms from four [Fe(phen)(CN)4]-
      units build a distorted octahedral surrounding Mn(II) (2) and Zn(II) (3). The M-O
      bond lengths are 2.185(3) (2) and 2.105(3) A (3), whereas the M-N bond distances
      vary in the ranges 2.210(3)-2.258(3) A (2) and 2.112(3)-2.186(3) A (3). The
      structure of the [Fe(phen)(CN)4]- complex ligand in 2 and 3 is as in 1. The
      shorter intrachain Fe-M distances through bridging cyano are 5.245(5) and
      5.208(5) A in 2 and 5.187(1) and 5.132(1) A in 3. The magnetic properties of 1-3
      have been investigated in the temperature range 2.0-300 K. Complex 1 is a low
      spin iron(III) complex with an appreciable orbital contribution. The magnetic
      properties of 3 correspond to the sum of two magnetically isolated spin triplets,
      the magnetic coupling between the low-spin iron(III) centers through the -CN-Zn
      NC- bridging skeleton (iron-iron separation larger than 10.2 A) being negligible.
      More interestingly, 2 exhibits one-dimensional ferrimagnetic behavior due to the
      noncompensation of the local interacting spins (S(Mn) = 5/2 and S(Fe) = 1/2)
      which interact antiferromagnetically through bridging cyano groups. A comparison
      between the magnetic properties of the isostructural compounds 2 and 3 allow us
      to check the antiferromagnetic coupling in 2.

PMID- 11304152
TI  - Autoionization of homogeneous nickel(II) diphosphane hydrogenation catalysts. An
      NMR study and crystal structures of [Ni(o-MeO-dppe)I2] and [Ni(o-MeO
      dppe)I2](PF6)2.
AB  - The synthesis of a number of nickel(II) complexes containing the didentate
      phosphane ligand 1,2-bis(di(o-methoxyphenyl)phosphino)ethane (o-MeO-dppe) is
      reported. Two types of complexes have been synthesized, i.e., the mono(chelate)
      complex (1) of the general formula [Ni(o-MeO-dppe)X2] (where X = Cl, Br or I) and
      the bis(chelate) complex (2) of the general formula [Ni(o-MeO-dppe)2]Y2 (where Y
      = PF6 or trifluoroacetate (TFA)). These complexes have been characterized using
      electronic absorption and NMR spectroscopy. The structures of the mono(chelate)
      complex [Ni(o-MeO-dppe)I2] (1c) and of the bis(chelate) complex [Ni(o-MeO
      dppe)2](PF6)2 (2e) have been determined by X-ray crystallography. [Ni(o-MeO
      dppe)I2] crystallizes in the monoclinic space group P2(1)/c with Z = 4, a =
      12.1309(1) A, b = 16.5759(3) A, c = 17.6474(2) A, beta = 119.3250(10) degrees.
      [Ni(o-MeO-dppe)2](PF6)2 crystallizes in the monoclinic space group C2/c with Z =
      4, a = 22.5326(3) A, b = 13.6794(2) A, c = 21.7134(3) A, beta = 107.1745(7)
      degrees. In both structures the nickel ion is in a square-planar geometry with a
      NiP2I2 and NiP4 chromophore, respectively. Using 1H and 31P[1H] NMR spectroscopy
      the behavior of the complexes in various solvents has been studied. It appears
      that in solution these nickel complexes are involved in an autoionization
      equilibrium: 2[Ni(o-MeO-dppe)X2] <==>[Ni(o-MeO-dppe)2](2+) + ["NiX(4)"](2-). The
      ionized complex (3) consists of a cationic unit in which a nickel atom is
      surrounded by two didentate phosphane ligands, and an anionic unit that
      stoichiometrically consists of a nickel atom and four anions. The position of the
      autoionization equilibrium is highly dependent on the anion and the solvent used.
      In a polar solvent in combination with weakly coordinating anions only the
      ionized complex is observed, whereas in an apolar solvent in combination with
      coordinating anions only the mono(chelate) complex occurs. A comparison of the
      behavior of o-MeO-dppe with its unsubstituted analogue dppe in combination with
      nickel(II) acetate using 31P[1H] NMR spectroscopy shows that the latter is more
      readily oxidized.

PMID- 11304153
TI  - Stabilization of isolated mixed-valence trimers in a novel nickel dithiolene
      complex with CF2 substituents.
AB  - The preparation of the novel paramagnetic nickel dithiolene complex Ni(F2pdt)2-*
      (F2pdt2-: 2,2-difluoro-1,3-propanediyldithioethylene-1,2-dithiolate) and its X
      ray crystal structure as n-Bu4N+ salt are described. (n-Bu4N)[Ni(F2pdt)2] (2)
      crystallizes in the orthorhombic system, space group Pna2(1) with a = 21.379(4)
      A, b = 8.9702(18) A, and c = 18.527(4) A. The radical anions are isolated from
      each other by the bulky n-Bu4N+ cations and exhibit a Curie-type magnetic
      behavior. Two reversible redox waves corresponding to the redox couples
      Ni(F2pdt)2(2-/-*) and Ni(F2pdt)2(-*/0) are observed at -0.55 and 0.30 V vs SCE,
      illustrating the electron withdrawing effect of the CF2 substituents. As a
      consequence, (TTF)3(BF4)2 oxidation of the radical anion does not afford the
      neutral Ni(F2pdt)2(0) but a TTF salt formulated as [TTF](3)[Ni(F2pdt)2]3[CH2Cl2].
      It crystallizes in the triclinic system, space group P1 with a = 12.330(3) A, b =
      12.726(3) A, c =15.706(3) A, alpha = 91.10(3), beta = 110.78(3), and gamma =
      116.01(3). Donor and acceptor moieties are organized into (TTF)3(2+) and
      [Ni(F2pdt)2]3(2-) trimers whose dicationic and dianionic charges have been
      inferred from the intramolecular bond lengths evolution and the singlet-triplet
      magnetic behavior. These trimers arrange orthogonally to each other into chess
      board-like slabs, characterized by a segregation of the CF2 fragments and further
      stabilized by weak C-H.F interactions. Extended Huckel calculations show that
      only the nickel dithiolene complex trimer actually contributes to the magnetic
      susceptibility.

PMID- 11304154
TI  - Synthesis and characterization of a new family of electroactive alkali metal
      doped mesoporous Nb, Ta, and Ti oxides and evidence for an Anderson transition in
      reduced mesoporous titanium oxide.
AB  - Recently we reported that mesoporous niobium oxide can be chemically reduced by
      Na-naphthalene while fully retaining its mesostructure. This was the first report
      of a molecular sieve acting as a stoichiometric electron acceptor. Herein we
      expand on the initial work by presenting a detailed study on Li-, Na-, K-, Rb-,
      and Cs-reduced samples of mesoporous Nb oxide, as well as Li-reduced mesoporous
      Ta and Ti oxides. While the Nb- and Ta-based materials fully retained their
      structure on reduction as determined by X-ray diffraction (XRD) and nitrogen
      adsorption, the Li-reduced Ti material retained high surface area and narrow pore
      size distribution, but lost its diffraction pattern, indicating an increased
      level of disorder in this material. X-ray photoelectron spectroscopy (XPS) and UV
      visible reflectance spectroscopy revealed that all reduced mesoporous oxides
      studied have a similar electronic structure, corresponding to the presence of a
      disordered impurity band in the material lying between the valence band and the
      conduction band. Electron paramagnetic resonance (EPR) studies suggest that the
      electron in this impurity level is unpaired and best described as a free
      electron, only loosely bound to the alkali or transition metal. SQUID
      magnetometry showed that all reduced materials are paramagnetic, further
      confirming the presence of unpaired electrons in the structure. All materials in
      this study were insulating with the exception of the Li-reduced mesoporous Ti
      material, which was highly conducting, possibly due to an Anderson transition.
      Electrochemical studies on the unreduced mesoporous oxides demonstrated that
      while the Ta and Nb materials are capacitors with only a small degree of
      reversible electrochemical behavior in the bulk sample, the Ti material was an
      electrical conductor with fully reversible redox behavior.

PMID- 11304155
TI  - Structure and optical properties of several organic-inorganic hybrids containing
      corner-sharing chains of bismuth iodide octahedra.
AB  - Two organic-inorganic bismuth iodides of the form (H3N-R-NH3)BiI5 are reported,
      each containing long and relatively flexible organic groups, R. The norganic
      framework in each case consists of distorted BiI6 octahedra sharing cis vertexes
      to form zigzag chains. Crystals of (H3NC18H24S2NH3)BiI5 were grown from a slowly
      cooled ethylene glycol/2-butanol solution containing bismuth(III) iodide and
      AETH.2HI, where AETH = 1,6-bis[5'-(2' '-aminoethyl)-2'-thienyl]hexane. The new
      compound, (H2AETH)BiI5, adopts an orthorhombic (Aba2) cell with the lattice
      parameters a = 20.427(3) A, b = 35.078(5) A, c = 8.559(1) A, and Z = 8. The
      structure consists of corrugated layers of BiI5(2-) chains, with Bi-I bond
      lengths ranging from 2.942(3) to 3.233(3) A, separated by layers of the organic
      (H2AETH)(2+) cations. Crystals of the analogous (H3NC12H24NH3)BiI5 compound were
      also prepared from a concentrated aqueous hydriodic acid solution containing
      bismuth(III) iodide and the 1,12-dodecanediamine (DDDA) salt, DDDA.2HI.
      (H2DDDA)BiI5 crystallizes in an orthorhombic (Ibam) cell with a = 17.226(2) A, b
      = 34.277(4) A, c = 8.654(1) A, and Z = 8. The Bi-I bonds range in length from
      2.929(1) to 3.271(1) A. While the inorganic chain structure is nearly identical
      for the two title compounds, as well as for the previously reported
      (H3NC6H12NH3)BiI5 [i.e., (H2DAH)BiI5] structure, the packing of the chains is
      strongly influenced by the choice of organic cation. Optical absorption spectra
      for thermally ablated thin films of the three organic-inorganic hybrids
      containing BiI5(2-) chains are reported as a function of temperature (25-290 K).
      The dominant long-wavelength feature in each case is attributed to an exciton
      band, which is apparent at room temperature and, despite the similar inorganic
      chain structure, varies in position from 491 to 541 nm (at 25 K).

PMID- 11304156
TI  - Structures and related properties of AgX bearing 3,3'-thiobispyridine (X- = NO3-,
      BF4-, CLO4-, and PF6-.
AB  - Infinite molecular helices [Ag(3,3'-Py2S)]X (3,3'-Py2S = 3,3'-thiobispyridine; X-
      = BF4-, ClO4-, and PF6-) have been rationally constructed or induced.
      Crystallographic characterization (X- = BF-, monoclinic P2(1)/n, a = 8.946(3) A,
      b = 14.130(2) A, c = 10.124(2) A, beta = 107.83(2) degrees, V = 1218.3(5) A3, Z =
      4, R = 0.0351; X- = ClO4-, monoclinic P2(1)/n, a = 8.884(1) A, b = 14.305(3) A, c
      = 10.110(1) A, beta = 106.78(1) degrees, V = 1230.1(3) A3, Z = 4, R = 0.0417; X-
      = PF6-, monoclinic P2(1)/c, a = 10.959(2) A, b = 9.808(2) A, c = 14.065(3) A,
      beta = 112.03(2) degrees, V = 1401.4(5) A3, Z = 4, R = 0.0442) reveals that the
      skeletal structure is an oblong cylindrical cationic helix consisting of
      alternating Ag(I) and 3,3'-Py2S species and that its counteranions are pinched in
      two columns inside each helix. The formation of the helical coordination polymer
      appears to be primarily associated with a suitable combination of the skewed
      conformer of 3,3'-Py2S and the potential linear geometry of the N-Ag(I)-N bond.
      However, the framework of the nitrate analogue [Ag(3,3'-Py2S)NO3] (monoclinic
      P2(1)/c, a = 8.177(2) A, b = 10.291(1) A, c = 14.771(2) A, beta = 102.19(1)
      degrees, V = 1214.9(4) A3, Z = 4, R = 0.0300) is a two-dimensional network
      consisting of an 18-membered ring unit, where each 3,3'-Py2S acts as a N,N',S-
      tridentate ligand connecting three tetrahedral silver(I) ions with the
      monodentate nitrate weakly bonded to the silver (Ag.O = 2.65(1) A) rather than
      acting as a counteranion. The anion exchange of [Ag(3,3'-Py2S)NO3] with BF4-,
      ClO4-, or PF6- has been accomplished in aqueous media. The two-dimensional
      networks are easily converted into the helices via the anion exchange, but the
      reverse anion exchange proceeds slightly. Thermal analyses indicate a
      relationship between the thermal stabilities and the structural properties.

PMID- 11304157
TI  - Adduct of acetylene at sulfur in an oxygen- and sulfur-bridged open cubane
      cluster complex of tungsten.
AB  - Formation of a single carbon-sulfur bond is described. The reaction of incomplete
      cubane-type sulfur and oxygen-bridged isothiocyanato tungsten cluster [W3(mu3
      S)(mu-O)(mu-S)2(NCS)9]5- (7) with acetylene affords [W3(mu3-S)(mu-O)(mu-S)(mu
      SCH=CH2)(NCS)9]4- (8). The cluster 8 has been isolated as K0.5(Hpy)3.5[W3(mu3
      S)(mu-O)(mu-S)(mu-SCH=CH2)(NCS)9] (8'), whose structure has been characterized by
      X-ray crystallography, electronic spectra, and 1H and 13C NMR spectroscopy.
      Crystal data of 8': triclinic system, space group P1, a = 14.465(5) A, b =
      17.353(3) A, c = 10.202(2) A, alpha = 90.98(1) degrees, beta = 108.59(2) degrees,
      gamma = 98.13(2) degrees, V = 2397.6(10) A(3), Z = 2, D(c) = 2.096 g cm(-3), Dm =
      2.08 g cm(-3), R (Rw) = 3.6 (5.5)% for 8786 reflections (I > 1.50 sigma(I)). The
      carbon-carbon distance is 1.27(1) A and is almost equidistant between ethylene
      (1.339 A) and acetylene (1.203 A). The electronic spectrum of 8' in 1.0 M HCl
      containing 1.5 M KSCN has a characteristic broad peak in the near-infrared region
      [lambda(max), nm (epsilon, M(-1) cm(-1)): 840 (650), 575 (1450)]. (1)H NMR and HH
      correlation spectroscopy (COSY) of 8' in CD3CN support the results of the X-ray
      structural analysis. The (1)H NMR spectrum shows three signals at 2.42 (1H, dd),
      4.84 (1H, d, J = 8.8 Hz), and 4.89 (1H, d, J = 16.2 Hz) ppm due to the mu-SCH=CH2
      moiety of 8'. The correlation spectrum shows spin couplings of the signal at 2.42
      ppm with the signals at 4.84 and 4.89 ppm. The mechanism of the formation of 8 is
      suggested to proceed through an intermediate with acetylene bridging two of the
      sulfur atoms.

PMID- 11304158
TI  - Syntheses and experimental studies on the relative stabilities of spiro, ansa,
      and bridged derivatives of cyclic tetrameric fluorophosphazene.
AB  - Reactions of (CF2CH2OSiMe3)2 and CF2(CF2CH2OSiMe3)2 with N4P4F8 (1) in a 1:2.5
      molar ratio resulted in the formation of monospiro compounds
      [(CF2CH2O)2PN](F2PN)3 (2) and [CF2(CF2)CH2O)2PN](F2PN)3 (4) as well as the
      intermolecular bridged compounds F7N4P4OCH2CF2CF2CH2OP4N4)F7 (3) and
      F7N4P4OCH2CF2CF2CF2CH2OP4N4F7 (5). An equimolar reaction of dilithiated 1,3
      propanediol with 1 resulted in the 1,3-ansa-substituted compound
      CH2(CH2O)2[P(F)N]2(F2PN)2 (6) as the major product in good yield. However, an
      analogous reaction of the dilithiated 1,3-propanedithiol with 1 gave only the
      spirocyclic compound CH2(CH2S)2(PN)(F2PN)3 (8). The molecular structures of 2 and
      6 were determined by single-crystal X-ray diffraction. In the presence of
      catalytic amounts of CsF in THF, the bridged compound 3 was converted to the
      spirocyclic compound 2 while the 1,3-ansa compound 6 under similar conditions
      transformed into the monospiro-substituted compound CH2(CH2O)2 (PN)(F2PN)3 (7).
      These transformations were monitored by time-dependent 19F and 31P NMR studies.

PMID- 11304159
TI  - Single-molecule magnets: Jahn-Teller isomerism and the origin of two
      magnetization relaxation processes in Mn12 complexes.
AB  - Several single-molecule magnets with the composition [Mn12O12(O2CR)16(H2O)x] (x =
      3 or 4) exhibit two out-of-phase ac magnetic susceptibility signals, one in the 4
      7 K region and the other in the 2-3 K region. New Mn12 complexes were prepared
      and structurally characterized, and the origin of the two magnetization
      relaxation processes was systematically examined. Different crystallographic
      forms of a Mn12 complex with a given R substituent exist where the two forms have
      different compositions of solvent molecules of crystallization and this results
      in two different arrangements of bound H2O and carboxylate ligands for the two
      crystallographically different forms with the same R substituent. The X-ray
      structure of cubic crystals of [Mn12O12(O2CEt)16(H2O)3]. 4H2O (space group P1)
      (complex 2a) has been reported previously. The more prevalent needle-form of
      [Mn12O12(O2CEt)16(H2O)3] (complex 2b) crystallizes in the monoclinic space group
      P2(1)/c, which at -170 degrees C has a = 16.462(7) A, b = 22.401(9) A, c =
      20.766(9) A, beta = 103.85(2) degrees, and Z = 4. The arrangements of H2O and
      carboxylate ligands on the Mn12 molecule are different in the two crystal forms.
      The complex [Mn12O12-(O2)CC6H4-p-Cl)16(H2O)4].8CH2Cl2 (5) crystallizes in the
      monoclinic space group C2/c, which at -172 degrees C has a = 29.697(9) A, b =
      17.708(4) A, c = 30.204(8) A, beta = 102.12(2) degrees, and Z = 4. The ac
      susceptibility data for complex 5 show that it has out-of-phase signals in both
      the 2-3 K and the 4-7 K ranges. X-ray structures are also reported for two
      isomeric forms of the p-methylbenzoate complex. [Mn12O12(O2CC6H4-p-Me)16(H2O)4].
      (HO2CC6H4-p-Me) (6) crystallizes in the monoclinic space group C2/c, which at 193
      K has a = 40.4589(5) A, b = 18.2288(2) A, c = 26.5882(4) A, beta = 125.8359(2)
      degrees, and Z = 4. [Mn12O12(O2CC6H4-p-Me)16(H2O)4].3(H2O) (7) crystallizes in
      the monoclinic space group I2/a, which at 223 K has a = 29.2794(4) A, b =
      32.2371(4) A, c = 29.8738(6) A, beta = 99.2650(10) degrees, and Z = 8. The Mn12
      molecules in complexes 6 and 7 differ in their arrangements of the four bound H2O
      ligands. Complex 6 exhibits an out-of-phase ac peak (chi(M)' ') in the 2-3 K
      region, whereas the hydrate complex 7 has a chi(M)' ' signal in the 4-7 K region.
      In addition, however, in complex 6, one Mn(III) ion has an abnormal Jahn-Teller
      distortion axis oriented at an oxide ion, and thus 6 and 7 are Jahn-Teller
      isomers. This reduces the symmetry of the core of complex 6 compared with complex
      7. Thus, complex 6 likely has a larger tunneling matrix element and this explains
      why this complex shows a chi(M)' ' signal in the 2-3 K region, whereas complex 7
      has its chi(M)' ' peak in the 4-7 K region, i.e., the rate of tunneling of
      magnetization is greater in complex 6 than complex 7. Detailed 1H NMR experiments
      (2-D COSY and TOCSY) lead to the assignment of all proton resonances for the
      benzoate and p-methyl-benzoate Mn12 complexes and confirm the structural
      integrity of the (Mn12O12) complexes upon dissolution. In solution there is rapid
      ligand exchange and no evidence for the different isomeric forms of Mn12
      complexes seen in the solid state.

PMID- 11304160
TI  - Bimetallic reactivity. Preparation and properties of bimetallic complexes formed
      by binucleating ligands bearing 4- and 6-coordinate sites.
AB  - Four binucleating ligands bearing 4- and 6-coordinate sites employing phenolate
      bridges have been prepared. Bimetallic copper(II) and nickel(II) complexes of
      some of these ligands have been isolated and characterized. Crystal structures of
      two of the copper(II) complexes have been determined. A monometallic
      manganese(II) complex of one of these ligands was isolated. Upon exposure to
      dioxygen, acetonitrile solutions of the complex in the presence of chloride ions
      lead to the formation of a manganese(IV) complex. The crystal structure of this
      complex is reported, and it is shown that the metal is in the 4-coordinate ligand
      site and is bound to two chloride ions.

PMID- 11304161
TI  - Synthesis, structural characterization, and conformational bias in solution of a
      sterically congested pyrophosphite: experimental and computational evidence for
      restricted rotation about an sp3-sp3 P-O single bond.
AB  - The synthesis and structural characterization of the sterically congested
      pyrophosphite 6-[(2,4,8,10-tetrakis(1,1-dimethylethyl)
      dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl)oxy]-2,4,8,10-tetrakis(1,1-dimethylethyl)
      dibenzo[d,f][1,3,2]dioxaphosphepin, 3, is described. In solution at room
      temperature, a single species was observed that was consistent with a
      pyrophosphite structure without any evidence for the tautomeric diphosphine
      monoxide. Below the coalescence temperature (T(C)), 0 degrees C, three
      atropisomers were observed with relative absolute configurations of (R,R,R),
      (R,S,R), and (R,R,S). Ring inversion of the seven-membered rings below the T(C)
      is slow on the NMR time scale, which leads to observable diastereoisomerism
      because of the presence of two independent stereoaxes (sp2-sp2 C-C single bond
      connecting the two aryl rings). Additionally, a rotation about an exocyclic P-O
      single bond connecting the two seven-membered rings, which constitutes a third
      stereoaxis, is slowed on the NMR time scale. In the X-ray crystal structure of 3,
      the solid-state conformation was found to be the same as the major conformation
      in solution below the T(C), namely, the (R,R,S) atropisomer. The results of a
      conformational search, performed with a specifically parametrized AMBER force
      field, were in agreement with the 31P NMR assignment of the major (R,R,S)
      atropisomer, which was found to be an energy minimum. Additionally, we could
      independently assign the relative configuration of the minor isomers based on the
      calculated results.

PMID- 11304162
TI  - Spin dimer analysis of the anisotropic spin exchange interactions in the
      distorted wolframite-type oxides CuWO4, CuMoO4-III, and Cu(Mo(0.25)W0.75)O4.
AB  - The distorted wolframite-type oxides CuWO4 and CuMoO4-III have a structure in
      which CuO4 zigzag chains, made up of cis-edge-sharing CuO6 octahedra, run along
      the c-direction and hence exhibit low-dimensional magnetic properties. We
      examined the magnetic structures of these compounds and their isostructural
      analogue Cu(Mo(0.25)W0.75)O4 on the basis of the spin-orbital interaction
      energies calculated for their spin dimers. Our study shows that these compounds
      consist of two-dimensional (2D) magnetic sheets defined by one superexchange
      (intrachain Cu-O-Cu) and three super-superexchange (interchain Cu-O.O-Cu) paths,
      the strongly interacting spin units of these 2D magnetic sheets are the two-leg
      antiferromagnetic (AFM) ladder chains running along the (a + c)-direction, and
      the spin arrangement between adjacent AFM ladder chains leads to spin
      frustration. The similarities and differences in the magnetic structures of
      CuWO4, CuMoO4-III, and Cu(Mo(0.25)W0.75)O4 were discussed by examining how
      adjacent AFM ladder chains are coupled via the superexchange paths in the 2D
      magnetic sheets and how adjacent 2D magnetic sheets are coupled via another
      superexchange paths along the c-direction. Our study reproduces the experimental
      finding that the magnetic unit cell is doubled along the a-axis in CuWO(4) and
      along the c-axis in CuMoO4-III and predicts that the magnetic unit cell should be
      doubled along the a- and b-axes in Cu(Mo(0.25)W0.75)O4. In the understanding of
      the strength of a super-superexchange interaction, the importance of the
      geometrical factors controlling the overlap between the tails of magnetic
      orbitals was pointed out.

PMID- 11304163
TI  - Thermodynamic stability and kinetic inertness of MS-325, a new blood pool agent
      for magnetic resonance imaging.
AB  - Stability constants were measured for complexes formed between a modified DTPA
      ligand and the metal ions Gd(III), Eu(III), Fe(III), Ca(II), Cu(II), and Zn(II)
      at 25 degrees C in 0.1 M NaClO4. The gadolinium complex of this ligand is MS-325,
      a novel blood pool contrast agent for magnetic resonance imaging currently
      undergoing clinical trials. Stability constants were determined by 4 different
      methods: direct pH titration, pH titration with competition by EDTA, competition
      with DTPA using an HPLC-MS detection system, and competition with Eu(III) by
      monitoring equilibrium by luminescence spectroscopy. The 1:1 stability constants,
      log beta101, are the following: Gd, 22.06 (23.2 in 0.1 M Me4NCl); Eu, 22.21; Fe,
      26.66; Ca, 10.45; Cu, 21.3; Zn, 17.82. The exchange kinetics of the Gd complex,
      MS-325, with the radioactive tracer (152,154)Eu were studied at 25 degrees C in
      0.1 M NaClO4. The exchange reaction has acid-dependent and acid-independent
      terms. The rate expression is given by the following: R = k(a)[GdL][H]2 +
      kb[GdL][Gd][H] + kc[GdL][Gd]. The rate constants were determined to be the
      following: k(a) = 1.84 x 10(6) M(-2) x min(-1), kb = 2.87 x 10(3) M(-2) x min(
      1), kc = 3.72 x 10(-3) M(-1) x min(-1). MS-325 is 2-3 times more stable than
      GdDTPA at pH 7.4 and is 10-100 times more kinetically inert.

PMID- 11304164
TI  - 203,205Tl NMR studies of crystallographically characterized thallium alkoxides. X
      ray Structures of [TI(OCH2CMe3)]4 and [TI(OAr)]infinity, where OAr = OC6H3(Me)2
      2,6 and OC6H3(CHMe2)2-2,6.
AB  - [Tl(OCH2Me)]4 (1) was reacted with excess HOR to prepare a series of [Tl(OR)]n,
      where OR = OCHMe2 (2, n = 4), OCMe3 (3, n = 4), OCH2CMe3 (4, n = 4), OC6H3(Me)2
      2,6 (5, n = infinity), and OC6H3(CHMe2)2-2,6 (6, n = infinity). Single-crystal X
      ray diffraction experiments revealed that in the solid state the alkoxide-ligated
      compound 4 adopts a cubane structure, whereas the aryloxide derivatives, 5 and 6,
      formed polymeric chains. Compounds 1-6 were also characterized by 203,205Tl
      solution and 205Tl solid-state NMR spectroscopy. In solution it was determined
      that 1-4 retained the [Tl-O]4 cube structure, whereas the polymeric species 5 and
      6 appeared to be fluxional. Variations in the solution and solid-state structures
      for the [Tl(OR)]4 cubes and polymeric [Tl(OAr)]infinity are influenced by the
      steric hindrance of the ligand. The acidity of the parent alcohol influences the
      degree of covalency at the Tl metal center, which is reflected in the 203,205Tl
      chemical shifts for 1-6.

PMID- 11304165
TI  - Kinetics and mechanisms of catalytic oxygen atom transfer with oxorhenium(V)
      oxazoline complexes.
AB  - The rhenium(V) monooxo complexes (hoz)2Re(O)Cl (1) and [(hoz)2Re(O)(OH2)][OTf]
      (2) have been synthesized and fully characterized (hoz = 2-(2'-hydroxyphenyl)-2
      oxazoline). A single-crystal X-ray structure of 2 has been solved: space group =
      P1, a = 13.61(2) A, b = 14.76(2) A, c = 11.871(14) A, alpha = 93.69(4) degrees,
      beta = 99.43(4) degrees, gamma = 108.44(4) degrees, Z = 4; the structure was
      refined to final residuals R = 0.0455 and Rw = 0.1055. 1 and 2 catalyze oxygen
      atom transfer from aryl sulfoxides to alkyl sulfides and oxygen-scrambling
      between sulfoxides to yield sulfone and sulfide. Superior catalytic activity has
      been observed for 2 due to the availability of a coordination site on the
      rhenium. The active form of the catalyst is a dioxo rhenium(VII) intermediate,
      [Re(O)2(hoz)2]+ (3). In the presence of sulfide, 3 is rapidly reduced to
      [Re(O)(hoz)2]+ with sulfoxide as the sole organic product. The transition state
      is very sensitive to electronic influences. A Hammett correlation plot with para
      substituted thioanisole derivatives gave a reaction constant rho of -4.6 +/- 0.4,
      in agreement with an electrophilic oxygen transfer from rhenium. The catalytic
      reaction features inhibition by sulfides at high concentrations. The equilibrium
      constants for sulfide binding to complex 2 (cause of inhibition), K2 (L x mol(
      1)), were determined for a few sulfides: Me2S (22 +/- 3), Et2S (14 +/- 2), and
      tBu2S (8 +/- 2). Thermodynamic data, obtained from equilibrium measurements in
      solution, show that the S=O bond in alkyl sulfoxides is stronger than in aryl
      sulfoxides. The Re=O bond strength in 3 was estimated to be about 20 kcal x mol(
      1). The high activity and oxygen electrophilicity of complex 3 are discussed and
      related to analogous molybdenum systems.

PMID- 11304166
TI  - Long-lived emissions from 4'-substituted Pt(trpy)Cl+ complexes bearing aryl
      groups. Influence of orbital parentage.
AB  - Pt(trpy)Cl+, where trpy denotes 2,2':6',2' '-terpyridine, is a versatile binding
      agent but has a limited photochemistry due to a short excited-state lifetime.
      However, this work shows that the introduction of aryl substituents at the 4'
      position of the trpy ligand drastically alters the picture. For the substituents
      phenyl, p-methoxyphenyl, 1-naphthyl, 2-naphthyl, 9-phenanthrenyl, and 1-pyrenyl,
      the ligand abbrevations are 4'-Ph-T, 4'-pMeOPh-T, 4'-Npl-T, 4'-Np2-T, 4'-Phe9-T,
      and 4'-Pyre1-T, respectively. Techniques utilized include electrochemistry as
      well as absorption and emission spectroscopies. While the lowest energy excited
      states of Pt(4'-Ph-T)Cl+ and the parent complex Pt(trpy)Cl+ exhibit mainly metal
      to-ligand charge-transfer (MLCT) character, the emitting state takes on aryl-to
      trpy intraligand charge-transfer (ILCT) character as the substituents become more
      electron-donating. Studies of Zn(trpy)Cl2, its aryl-substituted analogues, and
      the free ligands themselves provide information about the relative energies of
      participating ILCT and intraligand 3pi-pi excited states. Even though the
      emission energy decreases when larger aryl groups are present, the emission
      lifetime increases all the way from 85 ns for Pt(4'-Ph-T)Cl+ to 64 micros for
      Pt(4'-Pyre1-T)Cl+. (Data from deoxygenated, room-temperature dichloromethane
      solution.) Intraligand character appears to dominate in the case of Pt(4'-Pyre1
      T)Cl+, which is unique in the series in that it exhibits singlet and triplet
      emissions in solution. In aerated solution the complex shows prompt as well as
      delayed fluorescence. Finally, studies in donor media establish that the
      introduction of intraligand character inhibits solvent-induced exciplex
      quenching.

PMID- 11304167
TI  - Free energy of spin-crossover complexes calculated with density functional
      methods.

PMID- 11304168
TI  - Reaction of 2-(phenylazo)aniline with Na2PdCl4: formation of a 2-(phenylazo)imino
      complex of bivalent palladium.

PMID- 11304169
TI  - A highly convergent synthesis of a complex oligosaccharide derived from group B
      type III Streptococcus.
AB  - An efficient synthesis of a heptasaccharide derived from group B type III
      Streptococcus carrying an artificial spacer (1) is described. Rapid assembly of a
      protected heptasaccharide (16a) is accomplished from readily available building
      blocks 2-5 without a single protecting group manipulation between glycosylation
      steps. The synthetic strategy may be applied to the assembly of other branched
      complex oligosaccharides. The deprotected heptasaccharide 1 was coupled to a
      poly[N-(acryloyloxy)succinimide, and the resulting material will be used for the
      development of an ELISA assay to detect antibodies against GBS, type III in
      pregnant women.

PMID- 11304170
TI  - Biosynthesis of riboflavin. The reaction catalyzed by 6,7-dimethyl-8
      ribityllumazine synthase can proceed without enzymatic catalysis under
      physiological conditions.
AB  - 6,7-Dimethyl-8-ribityllumazine is the biosynthetic precursor of the vitamin,
      riboflavin. The biosynthetic formation of the lumazine by condensation of 5-amino
      6-ribitylamino-2,4(1H,3H)-pyrimidinedione and 3,4-dihydroxy-2-butanone 4
      phosphate is catalyzed by the enzyme, lumazine synthase. We show that the
      condensation reaction can proceed without enzyme catalysis in dilute aqueous
      solution at room temperature and neutral pH. The reaction rate is proportional to
      e (pH). The activation energy of the uncatalyzed reaction is E(a) = 46.3 kJ mol(
      )(1). The regioselectivity of the uncatalyzed reaction increases with pH and
      temperature (70% at 65 degrees C and pH 7.75). The data suggest partitioning of
      the uncatalyzed reaction via two different reaction pathways. The value of
      k(cat)/k(uncat) may be indicative for an entropy driven process for the enzyme
      catalyzed reaction.

PMID- 11304171
TI  - An improved method for the palladium-catalyzed amination of aryl iodides.
AB  - Aryl iodides are coupled with amines to give the corresponding arylamines in high
      yield in the presence of palladium, a suitable ligand, and NaOt-Bu.
      Functionalized aryl iodides give good yields of the corresponding arylamines when
      Cs(2)CO(3) is substituted as the base.

PMID- 11304172
TI  - Proton-lithium binding behavior of tris(2-((pyrid-2-ylmethyl)uredio)ethyl)amine.
AB  - Tris(2-((pyrid-2-ylmethyl)uredio)ethyl)amine (2) and its perchlorate salt,
      2.HClO(4), bind with Li+ in nitromethane in a 1:1 fashion. The stability
      constants of K(Li+) and K(H)(Li+) were found to be 112 +/- 25 and 130 +/- 30 M(
      )(1) in CD(3)NO(2), respectively. Formation of the 1:1 complexes were further
      evidenced by electrospray ionization mass spectrometry (ESI-MS). The slight
      increase, or at least the same order of magnitude, of K(H)(Li+) compared to
      K(Li+) points to a remarkable preorganization of the protonated podand in
      2.HClO(4), that essentially overcomes the increased Columbic repulsion occurring
      on complexation to Li+.

PMID- 11304173
TI  - Alpha-(trifluoromethyl)amine derivatives via nucleophilic trifluoromethylation of
      nitrones.
AB  - (Trifluoromethyl)trimethylsilane (TMSCF(3)) reacts with nitrones to afford alpha
      (trifluoromethyl)hydroxylamines protected as O-trimethylsilyl ethers. Potassium t
      butoxide initiates the nucleophilic trifluoromethylation. The reaction works best
      with alpha,N-diaryl nitrones, and the conditions are compatible with a range of
      substituents on the aryl groups. Acidic deprotection of the nitrone/TMSCF(3)
      adducts generates alpha-(trifluoromethyl)hydroxylamines. Catalytic hydrogenation
      of the adducts produces alpha-(trifluoromethyl)amines. Nitrone/TMSCF(3) adducts
      with strong electron-withdrawing groups on the alpha-aryl ring or heterocyclic
      alpha-aryl groups undergo an elimination/addition sequence to generate
      alpha,alpha-bis(trifluoromethyl)amines. Nitrones with alkyl groups bound directly
      to the 1,3-dipolar moiety fail to react with TMSCF(3), but trifluoromethylation
      of beta,gamma-unsaturated nitrones followed by reduction of the double bond can
      circumvent this limitation.

PMID- 11304175
TI  - Parallel synthesis of novel heteroaromatic acromelic acid analogues from kainic
      acid.
AB  - A range of new C-4 heteroaromatic acromelic acid analogues has been synthesized
      in a parallel fashion from (-)-alpha-kainic acid 1. Protection of the amine and
      carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol
      ether 9, generated regiospecifically from the methyl ketone 8 using "kinetic"
      conditions, was brominated in situ with phenyltrimethylammonium perbromide to
      give the key alpha-bromo ketone 10. Parallel cyclization reactions of bromo
      ketone 10 with thioamides and thioureas were then performed. The aromatic
      heterocyclic derivatives 11a-d and 19 produced were deprotected to give the new
      kainoid amino acids 6a-d and 25 in excellent yield. Compounds 6a and 6c show
      strong binding to the kainate receptor. Reaction of 10 with alternative
      condensing agents was also briefly investigated.

PMID- 11304174
TI  - Antineoplastic agents. 450. Synthesis of (+)-pancratistatin from (+)-narciclasine
      as relay(1a).
AB  - (+)-Narciclasine (2) available in quantity from certain Amaryllidaceae species or
      by total synthesis was employed as a precursor for a 10-step synthetic conversion
      (3.6% overall yield) to natural (+)-pancratistatin (1a). The key procedures
      involved epoxidation of natural (+)-narciclasine (2) to epoxide 6, reduction to
      diol 8, and formation of cyclic sulfate 12 and its ring opening with cesium
      benzoate followed by saponification of the benzoate to afford (+)-pancratistatin
      (1a).

PMID- 11304176
TI  - 1H NMR study of protected and unprotected kainoid amino acids: facile assignment
      of C-4 stereochemistry.
AB  - The kainoid amino acids exhibit potent neuroexcitatory activity in the mammalian
      central nervous system. Around their pyrrolidine ring, a trans disposition
      between the C-2 and C-3 substituents and a cis relationship between the C-3 and C
      4 substituents are crucial for their potent biological activity. During synthetic
      studies into the kainoids, we have established a straightforward, empirical rule,
      which allows the facile assignment of C-4 stereochemistry to both protected and
      unprotected kainoids. When pairs of C-4 epimers are available, the rule indicates
      that, when their (1)H NMR spectra are compared, one of the methylene protons on
      the C-3 side chain appears at significantly lower chemical shift in the C-3, C-4
      cis isomer than the corresponding signal for the proton in the spectrum for the C
      3, C-4 trans isomer. In addition, the rule states that the difference in chemical
      shift between the two individual protons on the C-3 side chain of the C-3, C-4
      cis isomer is significantly greater than the corresponding difference for the C
      3, C-4 trans isomer. The rule is demonstrated for kainoids possessing an
      unsaturated substituent at C-4 and when comparing spectra in D(2)O for pairs of
      unprotected C-4 epimers, the spectra were recorded at approximately the same pD.

PMID- 11304177
TI  - Tandem transesterification and intramolecular cycloaddition of alpha
      methoxycarbonylnitrones with chiral acyclic allyl alcohols: systematic studies on
      the factors affecting diastereofacial selectivity of the cycloaddition.
AB  - Factors affecting the stereochemical course of the intramolecular cycloaddition
      of intermediary alpha-allyloxycarbonylnitrone resulting from transesterification
      of alpha-methoxycarbonylnitrones 1a-d with chiral allyl alcohols 5 or 6 were
      investigated systematically. It was found that the factors of diastereofacial
      selection are highly dependent on the geometries of the allyl alcohols. In the
      cases where primary or secondary chiral (Z)-allyl alcohols are used, A(1,3)
      strain arising from the chiralities in the (Z)-nitrone transition states of the
      intramolecular cycloaddtion is the most important factor. In contrast, in the
      case of the reaction using chiral nitrones 1c,d and (E)-allyl alcohols, steric
      interaction between the chiral N-substituent and the trans substituent of the
      olefin moiety in the intermediate is dominant. These aspects were applied to
      geometry-differentiated cycloaddition using a mixture of (E)-5 and (Z)-5. As a
      typical example, treatment of bulky 1b with a 1:1 mixture of (E)-5 and (Z)-5 in
      the presence of a catalytic amount of TiCl(4) and MS 4A gave 7b as the
      predominant product among four possible products.

PMID- 11304178
TI  - Ketene reactions with the aminoxyl radical tempo: preparative, kinetic, and
      theoretical studies.
AB  - Tetramethylpiperidinyloxy (TEMPO, TO*) reacts with ketenes RR(1)C=C=O generated
      by either Wolff rearrangement or by dehydrochlorination of acyl chlorides to give
      products resulting from addition of one TEMPO radical to the carbonyl carbon and
      a second to the resulting radical. Reactions of phenylvinylketenes 4b and 4f,
      phenylalkynylketene 4c, and the dienylketene AcOCMe=CHCH=CHCMe=C=O (11) occur
      with allylic or propargylic rearrangement. Even quite reactive ketenes were
      generated as rather long-lived species by photochemical Wolff rearrangement in
      isooctane solution, characterized by IR and UV, and used for kinetic studies. The
      rate constants of TEMPO addition to eight different ketenes have been measured
      and give a qualitative correlation of log k(2)(TEMPO) = 1.10 log k(H(2)O) -3.79
      with the rate constants for hydration of the same ketenes. Calculations at the
      B3LYP/6-311G//B3LYP/6-311G level are used to elucidate the ring opening of
      substituted cyclobutenones leading to vinylketenes and of 2,4-cyclohexadienone
      (17) forming 1,3,5-hexatrien-1-one (18).

PMID- 11304179
TI  - Chichibabin indolizine synthesis revisited: synthesis of indolizinones by
      solvolysis of 4-alkoxycarbonyl-3-oxotetrahydroquinolizinium ylides.
AB  - Solvolysis of 4-alkoxycarbonyl-(or 4-acyl)-3-oxo-1,2,3,4-tetrahydroquinolizinium
      ylides (1-4) was studied and three types of reactions were found to proceed
      competitively. Thus, alcoholysis afforded the Chichibabin rearrangement products,
      2,3-dihydro-2-indolizinones (5-8), solvolysis in trifluoroethanol or in aqueous
      methanol caused ring opening (and subsequent ester cleavage) to 2
      alkoxycarbonylethylpyridinium-1-acetates 10, 15, and 16, and hydrolysis resulted
      in ring opening to 1-alkoxycarbonylmethylpyridinium-2-propionates 11 or 13 (and
      subsequently to 12 or 14). Characteristically, all the types of reactions
      proceeded significantly faster with t-butoxycarbonyl substituted ylides than with
      smaller alkoxycarbonyl substituted ones. The general mechanism for the
      solvolysis, involving a ketene intermediate, is proposed based on kinetic
      measurements.

PMID- 11304180
TI  - Preparation of 4'-substituted thymidines by substitution of the thymidine 5'
      esters.
AB  - tert-Butyl thymidylate 3 was prepared from thymidine 1 in six steps and 67%
      overall yield. When the lithium trianion of 3 (prepared by treatment of 3 with
      excess LDA and then excess tert-butyllithum) is reacted with electrophiles,
      trapping occurs stereoselectively from either the alpha- or beta-face depending
      on the electrophile (Scheme 1). Deuterioacetic acid in deuteriomethanol affords
      mainly the alpha-deuterated product (4a/4b = 2.4:1) while all other
      electrophiles, e.g., phenylselenenyl chloride, allyl bromide, and N
      fluorobenzenesulfonimide (NFSI), give predominately (or completely) the products
      of attack from the beta-face (5bcd/4bcd = 3.7:1 to 100:0). The structures of the
      products were determined by coupling constant analysis of both the initial
      compounds and the diols 6bcd prepared by ester reduction and by formation of the
      acetonides 7bc. The methyl ester of the 3'-epimer of thymidylic acid 9 was also
      prepared from thymidine 1 in nine steps and 74% overall yield. When the lithium
      trianion of 9 (prepared by treatment of 9 with excess LDA and then excess tert
      butyllithum) is reacted with electrophiles, trapping also occurs
      stereoselectively with attack on either the alpha- or beta-face depending on the
      electrophile (Scheme 2). Again, deuterioacetic acid in deuteriomethanol affords
      mainly the beta-deuterated product (11a/10a = 1.6:1) while all other
      electrophiles, e.g., phenylselenenyl chloride, methyl iodide, allyl bromide, and
      NFSI, gave predominately (or completely) the product of attack from the alpha
      face (8.7:1 to 100: 0). Again, the structures of the products were determined by
      coupling constant analysis of both the initial compounds, and the diols 12b-e
      were prepared by reduction of the ester and by formation of the acetonides 13bcd.
      A rationale has been developed using molecular mechanics calculations to explain
      the diastereoselectivity that involves staggered axial attack on the sp(2) carbon
      opposite to the pseudoaxial alkoxy group in the most stable half-chair
      conformation of the enolates, as shown in Schemes 3-5.

PMID- 11304181
TI  - Effect of progressive benzyl substitution on the conformations of aminocaproic
      acid-cyclized dipeptides.
AB  - The constraint of dipeptides into a beta-turn conformation can be accomplished by
      linking the two ends of a standard dipeptide with a linker derived from
      aminocaproic acid (Aca). To elucidate the possibility of using substituted Aca
      linkers in peptidomimetic design, a series of five macrocycles composed of a
      monobenzylated Aca linker (containing the benzyl group on each of the five
      methylene groups of the parent linker) and Gly-Gly were synthesized. The
      requisite linkers were made by regiochemically controlled ring expansion
      techniques (for substitution on Aca positions C-3, C-4, or C-5), an Evans
      alkylation route (for C-2), or by chain extension of L-phenylalanal (for C-6).
      The solution-phase conformations of the macrocycles were examined by NMR and CD
      techniques; in addition, crystal structures of the C-4- and C-6-benzyl
      substituted linkers were obtained. Four out of the five macrocycles were found to
      exist with the dipeptide portion taking up either a type II or II' beta-turn
      conformation, but the Gly-Gly unit in the compound derived from 4-benzyl-Aca did
      not correspond to one of the standard beta-turn types.

PMID- 11304182
TI  - Molecular clips based on propanediurea: exceptionally high binding affinities for
      resorcinol guests.
AB  - A series of new receptor molecules derived from 2,4,6,8
      tetraazabicyclo[3.3.1]nonane-3,7-dione (propanediurea) is described. These
      molecules possess a cavity which is defined by two nearly parallel aromatic side
      walls positioned on top of a bis-urea framework. The resulting "U-shaped" clip
      molecules are ideal hosts for the complexation of flat aromatic guest molecules.
      The affinity of these new propanediurea based molecular clips for
      dihydroxybenzene derivatives is exceptionally high, with association constants up
      to K(a) = 2 400 000 L mol(-)(1). Comparison of the binding mechanism of a variety
      of clip and half clip hosts, in conjunction with NMR, IR, and X-ray studies, has
      enabled the reason for this high binding to be elucidated. It is shown that
      subtle sub-angstrom changes in the geometry of the clip molecules have a great
      impact on their binding properties.

PMID- 11304183
TI  - First total synthesis of phenylpyridine analogues of the antimitotic rhazinilam.
AB  - The first synthesis of phenylpyridine analogues of rhazinilam and evaluation of
      these new structures as inhibitors of microtubule disassembly by interaction with
      tubulin are described. The synthesis is based on such key steps as picolinic
      metalation, hetero-ring cross-coupling and reduction of an acetyl group to an
      ethyl group. Elaboration of a quaternary picolinic carbon is one of the
      challenges of the synthesis. Biological evaluation of compounds bearing a
      quaternary picolinic carbon showed interactions with tubulin similar to (-)
      rhazinilam but at a lower level.

PMID- 11304184
TI  - Density functional theory calculations of the effect of fluorine substitution on
      the cyclobutylcarbinyl to 4-pentenyl radical rearrangement.
AB  - The effects of fluorine substitution on the cyclobutylcarbinyl to 4-pentenyl
      radical rearrangement and on the strain of cyclobutane have being studied using
      density functional theory, the ring-opening being modestly inhibited and the
      strain generally not greatly affected. Perfluorocyclobutane is predicted to have
      6 kcal/mol less strain than cyclobutane. Cyclizations of 1,1,2,2-tetrafluoro- and
      1,1,2,2,3,3-hexafluoro-4-pentenyl radicals should be significantly enhanced (
      approximately 2400 times faster) relative to the parent system. The calculations
      are consistent with the few experimental data available.

PMID- 11304185
TI  - Asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids using (S,S)
      cyclohexane-1,2-diol as a chiral auxiliary.
AB  - Diastereoselective alkylation of ethyl 2-methyl- and/or 2-ethylacetoacetates
      using the (S,S)-cyclohexane-1,2-diol as an acetal chiral auxiliary afforded enol
      ethers (2a-f and 5a-f) of 92->95% de in 31-70% yields. Removal of the cyclohexane
      1,2-diol with BF(3)-OEt(2) afforded beta-keto esters (3 and 6) bearing a chiral
      quaternary carbon. The beta-keto esters could be easily converted into optically
      active alpha-methylated and/or alpha-ethylated alpha,alpha-disubstituted amino
      acids (12 and 13) in 21-99% yields using Schmidt rearrangement.

PMID- 11304186
TI  - A modular approach for the synthesis of oligosaccharide mimetics.
AB  - To allow modular syntheses of oligosaccharide mimetics, the potentially
      trifunctional glycoside 7 was synthesized and used as a scaffold for the
      successive attachment of further monosaccharide derivatives to lead to the di-,
      tri-, and tetrasaccharide mimetics 11, 13, and 16. This synthetic strategy can
      also be used to prepare oligovalent neoglycoconjugates, e.g., 18, which contains
      nine mannosyl units. The applied concept implies numerous options for the
      synthesis of a wide array of structural variations, biolabeling, or solid-phase
      synthesis as well as combinatorial approaches.

PMID- 11304187
TI  - Boundary conditions on the partitioning of deaminatively generated benzyl
      cations.
AB  - Nitrogenous entity-separated ion pairs (NESIPs) containing benzyl cations,
      nitrogen gas, and pivalate anions were generated via thermal deamination of N
      benzyl-N-nitrosopivalamide. Some decompositions were performed in methanolic
      solutions saturated with selected nucleophiles: acetate, azide, or cyanide ions.
      Trace amounts of benzyl cyanide and tolunitriles were observed; no corresponding
      products were detected in the acetate and azide cases. Other decompositions were
      performed in the absence of traditional solvent but in the presence of the
      nucleophilic salts; again only poor cyanide interception of the cation was
      observed. The poor showing of the nucleophilic ions, when present, is discussed
      in the context of the lifetime of the cation, effective nucleophilicity, and cage
      effects in deamination.

PMID- 11304188
TI  - Thianthrene 5-oxide as a probe for the electronic character of oxygen-transfer
      reactions: re-interpretation of experiments required.
AB  - The electronic character of oxidants, i.e., whether they attack substrates in an
      electrophilic or nucleophilic way, has extensively been investigated using
      thianthrene 5-oxide (SSO) as probe. The SSO molecule has a sulfide group, which
      is attacked by electrophilic oxidants, and a sulfoxide moiety, which is oxidized
      by nucleophilic oxidants. This density-functional study has been carried out in
      order to gain insight into the origin of the chemo- and stereoselectivity of SSO
      oxidation. It has been found that the endo and exo stereoisomers of the
      thianthrene oxides interconvert via ring-inversion with moderate energy barriers.
      Thus, the stereoselectivity of SSO oxidation has to be interpreted with caution.
      Furthermore, a topological electron-density analysis of thianthrene 5-oxide
      reveals that there is an area of charge depletion at the sulfoxide group. The
      location of this area indicates that the attack of nucleophilic oxidants on SSO
      is sterically hindered. Therefore, the SSO probe makes oxidants such as
      dioxiranes appear to be more electrophilic than they actually are.

PMID- 11304189
TI  - Studies toward the total synthesis of clavulactone.
AB  - Synthetic studies directed toward a total synthesis of clavulactone are reported.
      In light of the analysis made in our previous work, cyclopentane 4a (a key
      intermediate in the present work) was synthesized through a radical-mediated ring
      closure of a rationally designed substrate 25. Using HWE reactions, the lower and
      upper side-chains of 4a were converted into an allyl chloride and an allyl
      cyanohydrin, respectively. Subsequent treatment of the allyl chloride/cyanohydrin
      in a highly diluted THF solution with sodium bis(trimethylsiliyl)amide led to
      intramolecular alkylation and thus completed a major endeavor in synthesizing the
      dolabellane framework, construction of the eleven-membered ring. SmI(2)-mediated
      lactonization as a model reaction for the formation of the alpha,beta-unsaturated
      delta-lactone segment of clavulactone is also described.

PMID- 11304190
TI  - Novel sparteine-mediated enantio-dichotomic formal synthesis of R-(-)- and S-(+)
      curcuphenol.
AB  - High and opposite enantiodiscriminations were observed between tertiary amides
      and secondary amides in the sparteine-mediated lateral metalation-allylation of 2
      ethyl-m-toluamide derivatives (2a, 2e). The results described above have been
      applied for the formal synthesis of both enantiomers of curcuphenol. The brief
      mechanistic studies suggested that stereoinformation was introduced after the
      deprotonation step.

PMID- 11304191
TI  - Novel synthesis of enantiomerically pure natural inositols and their
      diastereoisomers.
AB  - The various inositol polyphosphates have been found to trigger many important
      biological processes. Although the knowledge of this phosphoinositide signaling
      system has been discovered in the past 10 years, many factors remain unclear. For
      this reason, there is an increased demand for supplies of D-myo-inositol and
      particularly of novel analogues to investigate these biological mechanisms in
      more detail. Herein, we report the efficient syntheses of all diastereoisomers of
      inositol starting with 6-O-acetyl-5-enopyranosides. Conversion of 6-O-acetyl-5
      enopyranosides into the corresponding substituted cyclohexanones (Ferrier-II
      rearrangement) was found to proceed efficiently with a catalytic amount of
      palladium dichloride. Stereoselective reduction of beta-hydroxy ketones obtained
      provided the precursors to all inositol diastereoisomers in good to excellent
      yields and with high stereoselectivities. Good accessibility of these
      enantiomerically pure inositol diastereoisomers results in the efficient
      syntheses of D-myo-inositol 1,4,5-trisphosphate and D-myo-inositol 1,3,4,5
      tetrakisphosphate.

PMID- 11304192
TI  - The 4,4'-(1,2-ethanediyl)bisbenzyl biradical: its generation, detection, and
      (photo)chemical behavior in solution.
AB  - The 4,4'-(1,2-ethanediyl)bisbenzyl biradical (2) is clearly and efficiently
      generated by photolysis of [3.2]paracyclophane-2-one (8) in cyclohexane solution.
      This intermediate is also formed via two-photon processes from
      [2.2]paracyclophane (3) and 1,2-bis(4-chloromethylphenyl)ethane (4). The products
      arising thermally from biradical 2 are [2.2]paracyclophane and
      [2.2.2.2]paracyclophane (11) (under high-intensity conditions). Furthermore, two
      laser two-color flash photolysis shows that biradical 2 is photostable in
      solution at room temperature. Thus, formation of p-xylylene (1) from 2 occurs
      neither thermally nor photochemically.

PMID- 11304193
TI  - Synthesis of polyazamacrocyclic compounds via modified Richman-Atkins cyclization
      of beta-trimethylsilylethanesulfonamides.
AB  - The Richman-Atkins cyclization remains one of the most widely used methods for
      the preparation of macrocyclic polyamines. The use of beta
      trimethylsilylethanesulfonamides (SES-sulfonamides) for the preparation of
      polyazamacrocyclic compounds is described. This expands existing Richman-Atkins
      sulfonamide macrocyclization methodology, and it successfully enables preparation
      of labile polyaza[n](1,4)naphthalenophanes and polyaza[n](9,10)anthracenophanes,
      not previously available in appreciable quantities.

PMID- 11304194
TI  - Polarity of the transition state controls the reactivity of related charged
      phenyl radicals toward atom and group donors.
AB  - Polar effects are demonstrated to be a key factor in controlling the reactivities
      of related charged phenyl radicals in different exothermic atom and group
      abstraction reactions in the gas phase. The effects of various meta substituents
      on the phenyl radicals' reactivity were probed via the measurement of bimolecular
      reaction rate constants by using Fourier transform ion cyclotron resonance mass
      spectrometry. This approach requires an additional, charged substituent to be
      present in the phenyl radical to allow mass spectrometric manipulation. The m
      pyridinium group was chosen for this purpose. The substrates studied were allyl
      iodide, dimethyl disulfide, and tert-butyl isocyanide. Two of the reactions of
      interest, *I and *SCH(3) transfer, are thought to occur by concerted bimolecular
      homolytic substitution (S(H)2), and the third one, *CN transfer, by an
      addition/elimination mechanism. For all three substrates, the reaction rate was
      found to increase in the following order for the differently substituted phenyl
      radicals: CH(3) approximately H < Br approximately Cl approximately COOH < NO(2)
      approximately CN. This trend does not arise from differences in reaction
      exothermicities or bond dissociation energies but via lowering the reaction
      barrier by electronic effects. The stabilization of the transition state is
      attributed to its increased polar character. A semiquantitative measure of the
      barrier lowering effect for each substituent is obtained from its influence on
      the electron affinity of the charged radical, as the calculated (B3LYP/6-31+G(d))
      adiabatic electron affinities of the radical model systems (ammonium instead of
      pyridinium charge site) follow the same trend as the reactivities.

PMID- 11304195
TI  - Total synthesis of a conformationally constrained didemnin B analog.
AB  - The total synthesis of a didemnin B analogue containing a conformationally
      constrained replacement for the isostatine moiety is reported. Synthetic
      highlights include an improved preparation of 2-hydroxy-3-cyclohexenecarboxylic
      acid and a new strategy for accessing the macrocycle.

PMID- 11304196
TI  - Synthesis of cyclophanes via an intermolecular Pd-catalyzed enyne-diyne cross
      benzannulation approach.
AB  - Several novel types of cyclophanes were efficiently synthesized via an
      intermolecular palladium-catalyzed cross-benzannulation of cyclic enynes and
      diynes. These types of cyclophanes are not accessible through an intramolecular
      mode of the homo-benzannulation protocol, reported previously. Cyclic reactants
      (enynes and diynes) were readily prepared in reasonable yields from commercially
      available materials using known procedures. The fact that the cyclic Z-enyne 29,
      in contrast to its E-counterpart, underwent benzannulation to produce the
      cyclophane 28 brought additional support for the necessity of having an E
      hydrogen atom at the terminal olefin moiety of nonactivated enynes, which was
      found previously in the benzannulation of the acyclic substrates.

PMID- 11304197
TI  - Total synthesis of rutamycin B and oligomycin C.
AB  - The asymmetric synthesis of the macrolide antibiotics (+)-rutamycin B (1) and (+)
      oligomycin C (2) is described. The approach relied on the synthesis and coupling
      of the individual spiroketal fragments 3a and 3b with the C1-C17 polyproprionate
      fragment 4. The preparation of the spiroketal fragments was achieved using chiral
      (E)-crotylsilane bond construction methodology, which allowed the introduction of
      the stereogenic centers prior to spiroketalization. The present work details the
      synthesis of the C19-C28 and C29-C34 subunits as well as their convergent
      assembly through an alkylation reaction of the lithiated N,N-dimethylhydrazones 6
      and 8 to afford the individual linear spiroketal intermediates 5a and 5b,
      respectively. After functional group adjustment, these advanced intermediates
      were cyclized to their respective spiroketal-coupling partners 40 and 41. The
      requisite polypropionate fragment was assembled in a convergent manner using
      asymmetric crotylation methodology for the introduction of six of the nine
      stereogenic centers. The use of three consecutive crotylation reactions was used
      for the construction of the C3-C12 subunit 32. A Mukaiyama-type aldol reaction of
      35 with the chiral alpha-methyl aldehyde 39 was used for the introduction of the
      C12-C13 stereocenters. This anti aldol finished the construction of the C3-C17
      advanced intermediate 36. A two-carbon homologation completed the construction of
      the polypropionate fragment 38. The completion of the synthesis of the two
      macrolide antibiotics was accomplished by the union of two principal fragments
      that was achieved with an intermolecular palladium-(0) catalyzed cross-coupling
      reaction between the terminal vinylstannanes of the individual spiroketals 3a and
      3b and the polypropionate fragment 4. The individual carboxylic acids 46 and 47
      were cyclized to their respective macrocyclic lactones 48 and 49 under Yamaguchi
      reaction conditions. Deprotection of these macrolides completed the synthesis of
      the rutamycin B and oligomycin C.

PMID- 11304198
TI  - Conformational studies by dynamic NMR. 80.(1) cog-wheel effect in the
      stereolabile helical enantiomers of dimesityl sulfoxide and sulfone.
AB  - The (1)H NMR solution spectra of the title compounds display anisochronous lines
      for the o-methyl substituents below -170 degrees C, due to the existence of two
      propeller-like M and P conformational enantiomers. The free energies of
      activation for the interconversion were determined to be 4.5 and 5.0 kcal mol(
      )(1), respectively, for dimesityl sulfoxide and dimesityl sulfone. Molecular
      mechanics calculations indicate that the enantiomerization process occurs via a
      correlated rotation (cog-wheel effect) entailing a one-ring flip (gear-meshing)
      pathway. (13)C NMR (CP-MAS) spectra and X-ray diffraction show that these helical
      enantiomers are stable in the crystalline state.

PMID- 11304199
TI  - The first synthesis of enantiopure alpha-amino ketimines and amino aziridines.
AB  - Chiral 1-aminoalkyl chloromethyl ketimines 2 are synthesized in enantiomerically
      pure form starting from 1-aminoalkyl chloromethyl ketones 1 and different amines.
      Reduction of amino ketimines 2 and subsequent spontaneous cyclization affords
      aminoalkyl aziridines 3 with high diastereoisomeric excess and without detectable
      racemization.

PMID- 11304200
TI  - Hexaaminobenzene derivatives: synthesis and unusual oxidation behavior.
AB  - The syntheses and the electrochemical behavior of the monomeric peralkylated
      hexaamino(1,3)metacyclophane 4, the dimeric dodecaamino(1,3)cyclophane 5a, and
      the dodecaamino(1,3,5)cyclophane 6 are described. Electrochemical measurements
      show that the hexaaminobenzene units in 4 and 5a undergo an unusually slow two
      electron transfer attributed to the deformation of the rings into bis-cyanine
      cations when oxidized to the respective dication. Further oxidations to tri-,
      tetra-, and hexacationic units occur at more positive potentials. In the dimeric
      structures, no interaction between the rings can be seen in the (1,3)cyclophane,
      but strong interaction for the (1,3,5)cyclophane is observed.

PMID- 11304201
TI  - A study of C-F.M+ interaction: alkali metal complexes of the fluorine-containing
      cage compound.
AB  - The C-F.M(+) interaction was investigated by employing a cage compound 1 that has
      four fluorobenzene units. The NMR ((1)H, (13)C, and (19)F) spectra and X-ray
      crystallographic analyses of 1 and its metal complexes showed clear evidence of
      the interaction. Short C-F.M(+) distances (C-F.K(+), 2.755 and 2.727 A; C
      F.Cs(+), 2.944 and 2.954 A) were observed in the crystalline state of K(+) subset
      1 and Cs(+) subset 1. Furthermore, the C-F bond lengths were elongated by the
      interaction with the metal cations. By calculating Brown's bond valence, it is
      shown that the contribution of the C-F unit to cation binding is comparable or
      greater than the ether oxygen in the crystalline state. Representative
      spectroscopic changes implying the C-F.M(+) interaction were observed in the NMR
      ((1)H, (13)C, and (19)F) spectra. In particular, (133)Cs-(19)F spin coupling (J =
      54.9 Hz) was observed in the Cs(+) complex.

PMID- 11304202
TI  - Total syntheses of the benzodiazepine alkaloids circumdatin F and circumdatin C.
AB  - Total syntheses of circumdatin F and circumdatin C, which both possess a 3H
      quinazolin-4-one as well as a 1,4-benzodiazepin-5-one moiety, are described. A
      tripeptide derivative was synthesized as a key intermediate and dehydrated to a
      benzoxazine by reaction with triphenylphosphine, iodine, and a tertiary amine.
      The natural products were attained via rearrangements to an amidine intermediate,
      deprotection with 45% HBr in acetic acid, and cyclization on silica gel.

PMID- 11304203
TI  - Synthesis of novel 3'-C-methylene thymidine and 5-methyluridine/cytidine H
      phosphonates and phosphonamidites for new backbone modification of
      oligonucleotides.
AB  - Novel 5'-O-DMT- and MMT-protected 3'-C-methylene-modified thymidine, 5
      methyluridine, and 5-methylcytidine H-phosphonates 1-7 with O-methyl, fluoro,
      hydrogen, and O-(2-methoxyethyl) substituents at the 2'-position have been
      synthesized by a new effective strategy from the corresponding key intermediates
      3'-C-iodomethyl nucleosides and intermediate BTSP, prepared in situ through the
      Arbuzov reaction. The modified reaction conditions for the Arbuzov reaction
      prevented the loss of DMT- and MMT-protecting groups, and directly provided the
      desired 5'-O-DMT- and/or MMT-protected 3'-C-methylene-modified H-phosphonates 1-6
      although some of them were also prepared through the manipulation of protecting
      groups after the P-C bond formation. The modified Arbuzov reaction of 3'-C
      iodomethyl-5-methylcytidine 53, prepared from its 5-methyluridine derivative 42,
      with BTSP provided the 5-methylcytidine H-phosphonate 54, which was further
      transferred to the corresponding 4-N-(N-methylpyrrolidin-2-ylidene)-protected H
      phosphonate monomer 7. 5'-O-MMT-protected 3'-C-methylene-modified H-phosphonates
      5, 3, and 7 were converted to the corresponding cyanoethyl H-phosphonates 50, 51,
      and 56 using DCC as a coupling reagent. One-pot three-step reactions of 50, 51,
      and 56 provided the desired 3'-C-methylene-modified phosphonamidite monomers 8
      10. Some of these new 3'-methylene-modified monomers 1-10 have been successfully
      utilized for the synthesis of 3'-methylene-modified oligonucleotides, which have
      shown superior antisense properties including nuclease resistance and binding
      affinity to the target RNA.

PMID- 11304204
TI  - Isolation and characterization of all eight bisadducts of fulleropyrrolidine
      derivatives.
AB  - We report the isolation and characterization of bisadducts of fulleropyrrolidine
      derivatives. The compounds were characterized by means of a variety of
      spectroscopic techniques, including ES-MS, UV-vis, (1)H NMR, and (13)C NMR. The
      whole series of bisadducts was separated for the first time in the case of the
      bispyrrolidines, and the determination of their structure was obtained by NMR
      spectroscopy with the help of HMQC and HMBC techniques.

PMID- 11304205
TI  - 19F NMR chemical shifts. 1. Aliphatic fluorides.
AB  - The (19)F NMR shielding for the alkyl fluorides from methyl fluoride to tert
      butyl fluoride has been calculated using IGAIM and has been separated into the
      contribution from each of the molecular orbitals. The relatively large change in
      fluorine shielding, in contrast to the adjacent carbon, was found to be due to
      the tensor components normal to the C-F bond axis. As the number of adjacent p
      orbitals increases, the lone-pair p orbitals at fluorine become involved with MOs
      using these orbitals. The increase in the number of occupied orbitals associated
      with the fluorine leads to increased opportunities for mixing with virtual
      orbitals and to the increase in paramagnetic deshielding. The same pattern is
      seen on going from acetylene to 2-tert-butylacetylene and is also seen in the
      methyl (13)C shielding in the series ethane, propane, isobutane, and neopentane.
      The fluorine shielding in the series of fluoromethanes also decreases with
      increasing fluorine substitution. With carbon tetrafluoride, the decreased
      shielding arises from the highest occupied MO, which is a nonbonding linear
      combination of pure p functions at the fluorines.

PMID- 11304206
TI  - Hodgsonox, a new class of sesquiterpene from the liverwort Lepidolaena
      hodgsoniae. Isolation directed by insecticidal activity.
AB  - Hodgsonox (1), a new insecticidal sesquiterpene, has been isolated from the New
      Zealand liverwort Lepidolaena hodgsoniae. The structure was elucidated on the
      basis of 2D NMR analysis of 1 and a synthetic epoxide derivative (2). Hodgsonox
      represents a new class of sesquiterpene with a cyclopenta[5,1-c]pyran ring system
      fused to an oxirane ring. The combination of a mono- and a 1,1 disubstituted
      double bond flanking the oxygenated carbon of a the pyran ring is a unique
      structural feature. Hodgsonox is toxic to larvae of the blowfly Lucilia cuprina.

PMID- 11304208
TI  - 1-Oxaspiro[4.4]nonan-6-ones. Synthetic access via oxonium ion technology, optical
      resolution, and conversion into enantiopure spirocyclic alpha,beta-butenolides.
AB  - A general approach to the synthesis of enantiomerically pure spirocyclic
      alpha,beta-butenolides is presented where the fundamental framework is rapidly
      elaborated by acid- or bromonium ion-induced rearrangement of the carbinol
      derived by addition of 2-lithio-4,5-dihydrofuran to cyclobutanone. Subsequent
      resolution of the resulting ketones by either sulfoximine or mandelate acetal
      technology has been applied effectively. The availability of these building
      blocks makes possible in turn the acquisition of the enantiomers of dihydrofurans
      typified by 17, 35, and 38 and lactones such as 25 and 31, as well as the
      targeted title compounds. Complementary reductions of the early intermediates
      provide the added advantage that the alpha- and beta-stereoisomeric carbinol
      series can be obtained on demand. These capabilities have been coordinated to
      allow the crafting of any member of the series in relatively few steps.

PMID- 11304207
TI  - Diastereoselective synthesis of substituted tetrahydroquinoline-4-carboxylic
      esters by a tandem reduction-reductive amination reaction.
AB  - A diastereoselective synthesis of 1-methyl-2-alkyl- and 2-alkyl-1,2,3,4
      tetrahydroquinoline-4-carboxylic esters has been developed from methyl (2
      nitrophenyl)acetate (1). The method involves alkylation of 1 with an allylic
      halide, ozonolysis of the double bond, and catalytic hydrogenation. The final
      hydrogenation initiates a tandem sequence involving (1) reduction of the aromatic
      nitro group, (2) condensation of the aniline or hydroxylamine(8) nitrogen with
      the side chain carbonyl, (3) reduction of the resulting nitrogen intermediate,
      and (4) reductive amination of the tetrahydroquinoline with formaldehyde produced
      in the ozonolysis to give a methyl (+/-)-1-methyl-2-alkyl-1,2,3,4
      tetrahydroquinoline-4-carboxylate. Removal of the formaldehyde prior to
      hydrogenation gives the simple (+/-)-2-alkyl derivatives. The products are
      isolated in high yield as single diastereomers having the C-2 alkyl group cis to
      the C-4 carboxylic ester. The reaction has been extended to the synthesis of
      tricyclic structures with similar high diastereoselection.

PMID- 11304209
TI  - Palladium-catalyzed highly chemo- and regioselective formal [2+2+2] sequential
      cycloaddition of alkynes: a renaissance of the well known trimerization reaction?
AB  - A new concept of highly chemo- and regioselective formation of the benzene ring
      by a palladium-catalyzed formal [2 + 2 + 2] sequential intermolecular
      trimerization of alkynes is proposed. Homodimerization of terminal alkynes and
      subsequent [4 + 2] benzannulation with diynes gives tetrasubstituted benzenes in
      moderate to good yields. The introduction of two different alkynes (terminal and
      internal) in the first step of the sequence allows for construction of
      pentasubstituted benzenes from three different acyclic acetylenic units. In all
      cases the tetra- and pentasubstituted benzenes are formed as a single reaction
      product without being accompanied by any of regio- or chemoisomers. A significant
      acceleration of the sequential trimerization reaction in the presence of Lewis
      acid/phosphine combined system was observed. Mechanistic studies reveal that the
      Lewis acid assisted isomerization of the E-enyne formed in the first step of the
      sequence to the more reactive Z-isomer is responsible for the observed
      acceleration effect. The proposed methodology provides a conceptually new and
      synthetically useful route to multifunctional aromatic compounds.

PMID- 11304210
TI  - Asymmetric synthesis of cis-1,2-dialkenyl-substituted cyclopentanes via (-)
      sparteine-mediated lithiation and cycloalkylation of a 9-chloro-2,7-nonadienyl
      carbamate.
AB  - Herein we report our comprehensive results in enantioselective cyclopentane
      synthesis via stereogenic allyllithium compounds. The described cycloalkylation
      reaction starts with a (-)-sparteine-mediated asymmetric deprotonation of the 2,7
      alkadienyl carbamate 7e and leads to the enantioenriched (80% ee) and
      diastereomerically pure (dr = 99:1) cis-1,2-divinyl-cyclopentane 8, by a
      subsequent cyclization and elimination of lithium chloride. The reaction
      mechanism has been investigated by silylation and lithiodestannylation
      experiments and was found to represent a completely regioselective anti
      S(N)'S(E)'-reaction. Trapping of the vinyllithium intermediate 12 with various
      electrophiles under retention of the configuration at the double bond extends the
      field of application for this cyclization. We also applied this reaction as the
      key step in the enantioselective synthesis of (+)-dihydromultifidene (17).

PMID- 11304211
TI  - A facile synthesis of 3-substituted-2-aminothiophenes and 1,3-disubstituted-2
      methylthiopyrroles.
AB  - Electron-rich 3-functionalized-2-aminothiophenes 6 and 1,3-disubstituted-2
      methylthiopyrroles 10 were synthesized from substituted allyl benzotriazoles 2
      and isothiocyanates 3 via condensation and subsequent heterocyclization.

PMID- 11304213
TI  - N-boc-n-(benzotriazol-1-ylmethyl)benzylamine as a 1,1-dipole equivalent in
      stereoselective synthesis of 4,5-disubstituted imidazolidin-2-ones.

PMID- 11304214
TI  - Efficient syntheses of 1-amido-3-aryl- and 1-amido-3-alkylimidazo[1,5
      alpha]pyridines.

PMID- 11304212
TI  - N-functionalized benzotriazole-1-carboximidoyl chlorides: synthetic equivalents
      for isocyanide dichlorides.
AB  - Readily prepared N-functionalized benzotriazole-1-carboximidoyl chlorides are
      proposed as stable and novel isocyanide dichloride synthetic equivalents.
      Subsequent condensations of these new intermediates afford polysubstituted
      guanidines, S-aryl isothioureas, and 2-aminoquinazolin-4-thiones.

PMID- 11304215
TI  - Synthesis of novel alpha-amino-N-substituted thioacetimidates.

PMID- 11304216
TI  - A new synthetic route to protected alpha-hydrazinoesters in high optical purity
      using the Mitsunobu protocol.

PMID- 11304217
TI  - Meta selectivity in the Friedel-Crafts reaction induced by a faujasite-type
      zeolite.

PMID- 11304218
TI  - A new reagent system for modified Ullmann-type coupling reactions:
      NiCl(2)(PPh(3))(2)/PPh(3)/Zn/NaH/toluene.

PMID- 11304219
TI  - An efficient synthesis of pyrrolo[2,1-c][1,4]benzodiazepine. Synthesis of the
      antibiotic DC-81.

PMID- 11304220
TI  - Unprecedented sigmatropic rearrangements leading to 2,3-dihydro-1h-2-benzazepine
      3-carboxylic acid.

PMID- 11304221
TI  - Photoinduced C-C bond cleavage in dithiane-carbonyl adducts: a laser flash
      photolysis study.

PMID- 11304228
TI  - Linear and nonlinear experimental regimes of stochastic resonance.
AB  - We investigate the stochastic resonance phenomenon in a physical system based on
      a tunnel diode. The experimental control parameters are set to allow the control
      of the frequency and amplitude of the deterministic modulating signal over an
      interval of values spanning several orders of magnitude. We observe both a regime
      described by the linear-response theory and the nonlinear deviation from it. In
      the nonlinear regime we detect saturation of the power spectral density of the
      output signal detected at the frequency of the modulating signal and a dip in the
      noise level of the same spectral density. When these effects are observed we
      detect a phase and frequency synchronization between the stochastic output and
      the deterministic input.

PMID- 11304229
TI  - Role of entropy barriers for diffusion in the periodic potential.
AB  - Diffusion of a particle in the N-dimensional external potential which is periodic
      in one dimension and unbounded in the other N-1 dimensions is investigated. We
      find an analytical expression for the overdamped diffusion and study numerically
      the cases of moderate and low damping. We show that in the underdamped limit, the
      multidimensional effects lead to a reduction (compared to the one-dimensional
      motion) in the jump lengths between subsequent trappings of the atom at the
      minima of the external periodic potential. As an application, we consider the
      diffusion of a dimer adsorbed on the crystal surface.

PMID- 11304230
TI  - Patterns formed by spiral pairs in oscillatory media.
AB  - We investigate by numerical simulations the dynamics of spiral pairs which are
      found in oscillatory and excitable media as described by the complex Ginzburg
      Landau equation. Our simulations include two spiral pairs which approach each
      other and interact. The spirals typically exchange partners and form new pairs.
      This type of interaction gives rise to some patterns: a right-angle scattering
      pattern, a rotating state coming out of two traveling pairs, and a symmetric
      spiral lattice. The scenarios are compared to other conservative and dissipative
      systems where scattering at right angles is also observed.

PMID- 11304231
TI  - Levy flights from a continuous-time process.
AB  - Levy flight dynamics can stem from simple random walks in a system whose
      operational time (number of steps n) typically grows superlinearly with physical
      time t. Thus this process is a kind of continuous-time random walk (CTRW), dual
      to the typical Scher-Montroll model, in which n grows sublinearly with t. Models
      in which Levy flights emerge due to a temporal subordination allow one easily to
      discuss the response of a random walker to a weak outer force, which is shown to
      be nonlinear. On the other hand, the relaxation of an ensemble of such walkers in
      a harmonic potential follows a simple exponential pattern, and leads to a normal
      Boltzmann distribution. Mixed models, describing normal CTRW's in superlinear
      operational time and Levy flights under the operational time of subdiffusive
      CTRW's lead to a paradoxical diffusive behavior, similar to the one found in
      transport on polymer chains. The relaxation to the Boltzmann distribution in such
      models is slow, and asymptotically follows a power law.

PMID- 11304232
TI  - Territory covered by N random walkers on fractal media: the Sierpinski gasket and
      the percolation aggregate.
AB  - We address the problem of evaluating the number S(N)(t) of distinct sites visited
      up to time t by N noninteracting random walkers all starting from the same origin
      in fractal media. For a wide class of fractals (of which the percolation cluster
      at criticality and the Sierpinski gasket are typical examples) we propose, for
      large N and after the short-time compact regime, an asymptotic series for S(N)(t)
      analogous to that found for Euclidean media: S(N)(t) approximately S(N)(t)(1
      Delta). Here S(N)(t) is the number of sites (volume) inside a hypersphere of
      radius L[ln(N)/c]1/v where L is the root-mean-square chemical displacement of a
      single random walker, and v and c determine how fast 1-Gamma(t)(l) (the
      probability that a given site at chemical distance l from the origin is visited
      by a single random walker by time t) decays for large values of l/L: 1
      Gamma(t)(l) approximately exp[-c(l/L)(v)]. For the fractals considered in this
      paper, v=d(l)w/((d(l)w)-1), d(l)w being the chemical-diffusion exponent. The
      corrective term Delta is expressed as a series in ln(-n)(N)ln(m) ln(N) (with n>
      or =1 and 0< or =m< or =n), which is given explicitly up to n=2. This corrective
      term contributes substantially to the final value of S(N)(t) even for relatively
      large values of N.

PMID- 11304233
TI  - Molecular dynamics ensemble, equation of state, and ergodicity.
AB  - The variant of the NVE ensemble known as the molecular dynamics ensemble was
      recently redefined by Ray and Zhang [Phys. Rev. E 59, 4781 (1999)] to include the
      specification of a time invariant G (a function of phase and, explicitly, the
      time) in addition to the total linear momentum M. We reformulate this ensemble
      slightly as the NVEMR ensemble, in which R/N is the center-of-mass position, and
      consider the equation of state of the hard-sphere system in this ensemble through
      both the virial function and the Boltzmann entropy. We test the quasiergodic
      hypothesis by a comparison of old molecular dynamics and Monte Carlo results for
      the compressibility factor of the 12-particle, hard-disk systems. The virial
      approach, which had previously been found to support the hypothesis in the NVEM
      ensemble, remains unchanged in the NVEMR ensemble. The entropy S approach depends
      on whether S is defined through the phase integral over the energy sphere or the
      energy shell, the parameter straight theta being 0 or 1, respectively. The
      ergodic hypothesis is found to be supported for straight theta=0 but not for
      straight theta=1.

PMID- 11304234
TI  - General measures for signal-noise separation in nonlinear dynamical systems.
AB  - We propose the straight phi divergences from statistics and information theory
      (IT) as a set of separation indices between signal and noise in stochastic
      nonlinear dynamical systems (SNDS). The straight phi divergences provide a more
      informative alternative to the signal-to-noise ratio (SNR) and have the advantage
      of being applicable to virtually any kind of stochastic system. Moreover,
      straight phi divergences are intimately connected to various fundamental limits
      in IT. Using the properties of straight phi divergences, we show that the
      classical stochastic resonance (SR) curve can be interpreted as the performance
      of a nonoptimal, or mismatched, detector applied to the output of a SNDS. Indeed,
      for a prototype double-well system with forcing in the form of white Gaussian
      noise plus a possible embedded signal, the whole information loss can be
      attributed to this mismatch; an optimal detection procedure (for the signal)
      gives the same performance when based on the output as when based on the input of
      the system. More generally, it follows that, when characterizing signal-noise
      separation (or system performance) of SNDS in terms of criteria that do not
      correspond to IT limits, the choice of criterion can be crucial. The indicated
      figure of merit will then not be universal and will be relevant only to some
      family of applications, such as the classical (narrow-band SNR) SR criterion,
      which is relevant for narrow-band post processing. We illustrate the theory using
      simple SNDS excited by both wide- and narrow-band signals; however, we stress
      that the results are applicable to a much larger class of signals and systems.

PMID- 11304235
TI  - Critical properties of a branched polymer growth model.
AB  - We study the branched polymer growth model (BPGM) introduced by Lucena et al.
      [Phys. Rev. Lett. 72, 230 (1994)] in two dimensions. First the BPGM was simulated
      in very large lattices with concentrations of impurities q=0 and q=0.2. The
      scaling of the mass in chemical space gives accurate estimates of the critical
      branching probabilities b(c) and of the chemical dimensions Dc at criticality,
      improving previous results. Estimates of the fractal dimension D(F) at
      criticality are consistent with a universal value along the critical line. Our
      results for q=0 suggest small deviations of Dc and D(F) from the percolation
      values. We also simulated the BPGM in finite lattices of lengths between L=32 and
      L=512 for the same concentrations q. Using finite-size scaling techniques, we
      confirm the previous estimates of D(F) and the universality along the critical
      line, and obtain the correlation exponent nu=1.43+/-0.06. It proves that the BPGM
      is not in the same universality class of percolation in two dimensions. Finally,
      we simulate random walks on the critical polymers grown in very large lattices
      with q=0 and q=0.2, and obtain the random walk dimension Dw and the spectral
      dimension Ds. Dw is larger and Ds is smaller than the corresponding values in
      critical percolation clusters, due to the lower connectivity of the polymers. The
      scaling relation Ds=2D(F)/Dw is not satisfied, as observed in other tree-like
      structures.

PMID- 11304236
TI  - Left-sided multifractality in a binary random multiplicative cascade.
AB  - In this paper we study a binary random multiplicative cascade. Specifically, the
      cascade is used to produce and study left-sided multifractal random measures.
      Extensive numerical simulations of the random cascade process were undertaken and
      f(alpha) spectra obtained and compared with the analytical results. We believe
      that this model and approach can serve as a simple and fundamental tool in the
      analysis and understanding of physical systems possessing an underlying
      multiplicative structure.

PMID- 11304238
TI  - Dynamics of inelastic collapse.
AB  - We consider a particle randomly accelerated by Gaussian white noise on the half
      line x>0. The collisions of the particle with the wall at x=0 are inelastic. The
      velocities just before and after reflection are related by v(f)=-rv(i), where r
      is the coefficient of restitution. Cornell, Swift, and Bray have shown that for
      r<r(c)=e(-pi/sqrt[3])=0.163, there is inelastic collapse, i.e., boundary
      collisions localize the particle at x=0. The probability that the particle is not
      yet absorbed at the boundary after a time t decays, for long times, as t(
      straight theta(r)). The exponent straight theta(r) is calculated exactly. We also
      consider the case of "partial-survival" boundary conditions, i.e., elastic
      reflection with probability p and absorption with probability 1-p, and derive the
      analogous persistence exponent straight phi(p). The exact exponents satisfy the
      Swift-Bray conjecture straight theta(r)=straight phi(r(2straight theta(r))).

PMID- 11304239
TI  - Enhanced diffusion in smoothly modulated superlattices.
AB  - We investigate a superdiffusive behavior found in a quasiclassical model of a
      square-planar superlattice subjected to a perpendicular magnetic field. It is
      shown that certain accelerated domains are responsible for long trapping of
      tracers and setting them into near-ballistic motion. The mechanism of entrapment
      appears to be two-staged and multifractal. Relatively short trapping occurs in
      the vicinity of homoclinic tangles, created by intersections of stable and
      unstable manifolds of a hyperbolic fixed point, connected to itself. A structure
      of the quasitrap reveals families of multipulse solutions, doubly asymptotic to
      slow manifolds. The existence of orbits of this type was proved [G. Haller and S.
      Wiggins, Arch. Rational Mech. Anal. 130, 25 (1995)] for integrable two-degree-of
      freedom Hamiltonian systems with perturbation. We describe mixing dynamics in
      this region and examine characteristic escape time scales. More prolonged
      quasitrapping is due to sticking to resonant multilayered island chains that are
      found to accelerate ballistic transport. Phase-space dynamics is analyzed. We
      successfully employ a renewal process formalism to relate Poincare recurrences
      and coordinate variance asymptotics for both quasitraps and also justify the use
      of this formalism for the specific case of gradually increasing average velocity.

PMID- 11304240
TI  - Theory and computer simulation for the equation of state of additive hard-disk
      fluid mixtures.
AB  - A procedure previously developed by the authors to obtain the equation of state
      for a mixture of additive hard spheres on the basis of a pure fluid equation of
      state is applied here to a binary mixture of additive hard disks in two
      dimensions. The equation of state depends on two parameters which are determined
      from the second and third virial coefficients for the mixture, which are known
      exactly. Results are compared with Monte Carlo calculations which are also
      reported. The agreement between theory and simulation is very good. For the
      fourth and fifth virial coefficients of the mixture, the equation of state gives
      results which are also in close agreement with exact numerical values reported in
      the literature.

PMID- 11304241
TI  - Computer simulations of liquid silica: equation of state and liquid-liquid phase
      transition.
AB  - We conduct extensive molecular dynamics computer simulations of two models for
      liquid silica [the model of Woodcock, Angell and Cheeseman, J. Phys. Chem. 65,
      1565 (1976); and that of van Beest, Kramer, and van Santen, Phys. Rev. Lett. 64,
      1955 (1990)] to determine their thermodynamic properties at low temperature T
      across a wide density range. We find for both models a wide range of states in
      which isochores of the potential energy U are a linear function of T(3/5), as
      recently proposed for simple liquids [Rosenfeld and P. Tarazona, Mol. Phys. 95,
      141 (1998)]. We exploit this behavior to fit an accurate equation of state to our
      thermodynamic data. Extrapolation of this equation of state to low T predicts the
      occurrence of a liquid-liquid phase transition for both models. We conduct
      simulations in the region of the predicted phase transition, and confirm its
      existence by direct observation of phase separating droplets of atoms with
      distinct local density and coordination environments.

PMID- 11304242
TI  - Inhomogeneous integral equation approach to pair and triple correlations in a
      glass-forming simple liquid.
AB  - A simple model of glass-forming liquid modeled via Dzugutov's pair potential is
      studied by means of the triplet hypernetted chain approximation as formulated by
      Attard [P. Attard, J. Chem. Phys. 93, 7301 (1990)]. This system, which is known
      to be mostly dominated by microscopic icosahedral ordering, eludes a correct
      description in terms of classical two-body integral equation theories. However,
      it is found here that the simple hypernetted chain approximation when applied at
      the three-particle level can yield a correct semiquantitative description of both
      the pair and triplet structure of the supercooled state, capturing features which
      escape more sophisticated closures implemented on the two-particle level.

PMID- 11304243
TI  - Parametric Bragg resonances in waves on a shallow fluid over a periodically
      drilled bottom.
AB  - Bragg resonances involving strong interactions among Fourier wave components of a
      periodically drilled bottom and parametrically driven surface waves on a shallow
      liquid are experimentally shown to break down the secular dispersion relation of
      surface waves. When the fluid is sufficiently shallow, wave components that match
      reciprocal wave vectors of the bottom topography are dominant. Experimental
      evidence of band-gap phenomena in these surface waves are also shown. Moreover,
      the prevalence of Bragg resonances is so strong that one of them is excited
      anomalously within the band gap.

PMID- 11304244
TI  - Molecular-dynamics investigation of tracer diffusion in a simple liquid: test of
      the Stokes-Einstein law.
AB  - In this work, we study the diffusion of solute particles in the limit of infinite
      dilution in a solvent. An estimate is made of the solute concentration below
      which this limit is attained. We determine the range of the size and mass values
      of the solute particles where the solute diffusion coefficient is well estimated
      from the Stokes-Einstein formula. For these aims, extensive molecular-dynamics
      simulations are carried out for a model tracer-solvent system made up of 5324
      molecules including solvent and tracer molecules interacting through Lennard
      Jones potentials. The values of the viscosity coefficient, corrected for long
      time tail contributions, and the diffusion coefficients are obtained with high
      precision. Positive deviations from the Stokes-Einstein formula are observed as
      the size ratio or the mass ratio of the tracer to solvent molecules is lowered.
      For equal solvent and tracer molecular masses, the crossover to the hydrodynamics
      regime is found to occur when the size ratio is approximately 4. The results show
      a strong coupling between the size and mass effects on the tracer diffusivity,
      with the latter being predominant. An analysis of the molecular-dynamics data in
      the hydrodynamic regime shows that the Stokes-Einstein formula holds for this
      system with slip boundary conditions and the hydrodynamic radius equal to the
      cross radius between the tracer-solvent molecules. The friction coefficient is
      evaluated from the computed autocorrelation function of the force exerted by the
      fluid on the tracer molecule, following a scheme proposed by Lagar'kov and
      Sergeev; it is found that the latter criterion gives the correct diffusion
      coefficient only in the limits of high sizes and high masses.

PMID- 11304245
TI  - Mode-coupling theory for the glassy dynamics of a diatomic probe molecule
      immersed in a simple liquid.
AB  - Generalizing the mode-coupling theory for ideal liquid-glass transitions,
      equations of motion are derived for the correlation functions describing the
      glassy dynamics of a diatomic probe molecule immersed in a simple glass-forming
      system. The molecule is described in the interaction-site representation and the
      equations are solved for a dumbbell molecule consisting of two fused hard spheres
      in a hard-sphere system. The results for the molecule's arrested position in the
      glass state and the reorientational correlators for angular-momentum index l=1
      and l=2 near the glass transition are compared with those obtained previously
      within a theory based on a tensor-density description of the molecule in order to
      demonstrate that the two approaches yield equivalent results. For strongly
      hindered reorientational motion, the dipole-relaxation spectra for the alpha
      process can be mapped on the dielectric-loss spectra of glycerol if a rescaling
      is performed according to a suggestion by Dixon et al. [Phys. Rev. Lett. 65, 1108
      (1990)]. It is demonstrated that the glassy dynamics is independent of the
      molecule's inertia parameters.

PMID- 11304246
TI  - Self-dynamic structure factor of dense liquids: theory and simulation.
AB  - The self-intermediate dynamic structure factor Fs(k,t) of liquid lithium near the
      melting temperature is calculated by molecular dynamics. The results are compared
      with the predictions of several theoretical approaches, paying special attention
      to the Lovesey model and the Wahnstrom and Sjogren mode-coupling theory. To this
      end the results for the Fs(k,t) second memory function predicted by both models
      are compared with the ones calculated from the simulations.

PMID- 11304247
TI  - Global models for moving contact lines.
AB  - We consider thin film flows driven by surface tension and gravity. Within the
      framework of the lubrication approximation, we study the contact line motion
      using global models where either precursor film or slip are allowed. We show that
      completely wetting films can be simulated under both conditions without requiring
      direct tracking of the contact line interface. We perform a comparative study of
      standard and positivity preserving numerical methods for these problems in one
      space dimension, with the ultimate goal of choosing the best method applicable to
      two-dimensional problems. We find a considerable computational advantage of the
      precursor film model over the slipping models.

PMID- 11304248
TI  - Distribution functions of a simple fluid under shear. II. High shear rates.
AB  - The distortion of structure of a simple, inverse 12 soft-sphere fluid undergoing
      plane Couette flow is studied by nonequilibrium molecular dynamics (NEMD) and
      equilibrium molecular dynamics (EMD) with a high-shear-rate version of the
      nonequilibrium (NE) potential obtained recently from the NE distribution function
      theory of Gan and Eu [Phys. Rev. A 45, 3670; 46, 6344 (1992)]. The theory
      suggests a NE potential under which the equilibrium structure of the fluid is
      that of a NE fluid, and also suggests a corresponding Ornstein-Zernike equation
      with its closure relations. As in the low-shear-rate case [Yu. V. Kalyuzhnyi, S.
      T. Cui, P. T. Cummings, and H. D. Cochran, Phys. Rev. E 60, 1716 (1999)] the
      agreement between EMD and the modified hypernetted chain version of the theory is
      good. Although the high-shear-rate version of the NE potential improves the
      agreement between NEMD and EMD results (in comparison with the low-shear-rate
      version), its predictions are still unsatisfactory. With the high-shear-rate NE
      potential, EMD gives qualitatively correct predictions only for the shift of the
      position of the first maximum of the NE distribution function. The corresponding
      changes in the magnitude of the first maximum predicted by EMD have an opposite
      direction in comparison with those predicted by NEMD. It is concluded that the NE
      potential used is not very successful, and more accurate models for the potential
      are needed.

PMID- 11304250
TI  - Effect of boundary conditions on diffusion in two-dimensional granular gases.
AB  - We analyze the influence of boundary conditions on numerical simulations of the
      diffusive properties of a two-dimensional granular gas. We show in particular
      that periodic boundary conditions introduce unphysical correlations in time that
      cause the coefficient of diffusion to be strongly dependent on the system size.
      On the other hand, in large enough systems with hard walls at the boundaries,
      diffusion is found to be independent of the system size. We compare the results
      obtained in this case with Langevin theory for an elastic gas. Good agreement is
      found. We then calculate the relaxation time and the influence of the mass for a
      particle of radius R(s) in a sea of particles of radius R(b). As granular gases
      are dissipative, we also study the influence of an external random force on the
      diffusion process in a forced dissipative system. In particular, we analyze
      differences in the mean-square velocity and displacement between the elastic and
      inelastic cases.

PMID- 11304251
TI  - Evolution of force distribution in three-dimensional granular media.
AB  - Based on the discrete element method, the nature of normal contact force
      distribution and the effect of microstructure (contact fabric) on stresses in
      granular media sheared under constant mean stress condition is analyzed. The
      particles are tested in a periodic cell, having a nearly monodispersed system of
      spherical particles ("hard" and "soft"). The granular systems were initially
      isotropically compressed to have different solid fractions in order to obtain
      "dense" and "loose" samples. To study the nature of the force distribution, the
      granular medium was considered as both (i) noncohesive and (ii) with low values
      of interface energy. For the granular systems considered here, the nature of
      force distribution is shown to be dependent on shear history. The amount of
      interface energy introduced in the granular system does not seem to change the
      nature of normal force distribution significantly. However, it improves the
      postpeak stability in agreement with previous research [C. Thornton, Geotechnique
      50, 43 (2000)]. The simulation of systems subjected to quasistatic shearing, in
      general, reveals that in a hard system (both dense and loose), the normal contact
      force distribution (i) at "peak" shear strength is purely an exponential decay
      throughout the entire range of force scale that is used, and (ii) at "isotropic"
      and "steady" states, the contact normal force distribution is bimodal with forces
      greater than average decaying exponentially at both the states, while the forces
      less than average tend to be half-Gaussian at the "isotropic" state and a second
      order polynomial function at the "steady" state. For the soft (dense) system, the
      normal contact force distribution at "peak" shear strength is bimodal with forces
      greater than average decaying exponentially while the forces less than average
      tend to be a second-order polynomial function. However, for the soft system at
      both "isotropic" and "steady" states, the contact normal force distribution is
      half-Gaussian throughout the entire range of force scale that is used. It has
      been pointed out that in a granular system undergoing slow shearing, the shear
      strength of the system seems to depend on the ability of the material to form
      strong fabric anisotropy of contacts carrying strong (greater than average)
      force.

PMID- 11304252
TI  - Experimental study of solid-liquid-type transitions in vibrated granular layers
      and the relation with surface waves.
AB  - From pressure and surface dilation measurements, we show that a solid-liquid-type
      transition occurs at low excitation frequencies in vertically vibrated granular
      layers. This transition precedes subharmonic bifurcations from flat surface to
      standing wave patterns, indicating that these waves are in fact associated with
      the fluidlike behavior of the layer. At higher frequencies we show that another
      kind of subharmonic waves can be distinguished. These waves do not involve any
      lateral transfer of grains within the layer, and correspond to excitations for
      which the layer slightly bends alternately in time and space. These bending waves
      have very low amplitude, and we observe them in a vibrated two-dimensional layer
      of photoelastic particles.

PMID- 11304253
TI  - Diffusion as a mixing mechanism in granular materials.
AB  - We present several numerical results on granular mixtures. In particular, we
      examine the efficiency of diffusion as a mixing mechanism in these systems. The
      collisions are inelastic and to compensate the energy loss, we thermalize the
      grains by adding a random force. Starting with a segregated system, we show that
      uniform agitation (heating) leads to a uniform mixture of grains of different
      sizes. We define a characteristic mixing time tau(mix), and study theoretically
      and numerically its dependence on other parameters like the density. We examine a
      model for bidisperse systems for which we can calculate some physical quantities.
      We also examine the effect of a temperature gradient and demonstrate the
      appearance of an expected segregation.

PMID- 11304254
TI  - Higher-order glass-transition singularities in colloidal systems with attractive
      interactions.
AB  - The transition from a liquid to a glass in colloidal suspensions of particles
      interacting through a hard core plus an attractive square-well potential is
      studied within the mode-coupling-theory framework. When the width of the
      attractive potential is much shorter than the hard-core diameter, a reentrant
      behavior of the liquid-glass line and a glass-glass-transition line are found in
      the temperature-density plane of the model. For small well-width values, the
      glass-glass-transition line terminates in a third-order bifurcation point, i.e.,
      in a A3 (cusp) singularity. On increasing the square-well width, the glass-glass
      line disappears, giving rise to a fourth-order A4 (swallow-tail) singularity at a
      critical well width. Close to the A3 and A4 singularities the decay of the
      density correlators shows stretching of huge dynamical windows, in particular
      logarithmic time dependence.

PMID- 11304255
TI  - Equilibrium states and ground state of two-dimensional fluid foams.
AB  - We study the equilibrium energies of two-dimensional (2D) noncoarsening fluid
      foams, which consist of bubbles with fixed areas. The equilibrium states
      correspond to local minima of the total perimeter. We present a theoretical
      derivation of energy minima; experiments with ferrofluid foams, which can be
      either highly distorted, locally relaxed, or globally annealed; and Monte Carlo
      simulations using the extended large-Q Potts model. For a dry foam with small
      size variance we develop physical insight and an electrostatic analogy, which
      enables us to (i) find an approximate value of the global minimum perimeter,
      accounting for (small) area disorder, the topological distribution, and physical
      boundary conditions; (ii) conjecture the corresponding pattern and topology:
      small bubbles sort inward and large bubbles sort outward, topological charges of
      the same signs "repel" while charges of the opposite signs "attract;" (iii)
      define local and global markers to determine directly from an image how far a
      foam is from its ground state; (iv) conjecture that, in a local perimeter minimum
      at prescribed topology, the pressure distribution and thus the edge curvature are
      unique. Some results also apply to 3D foams.

PMID- 11304256
TI  - Magnetic-field-induced structural transitions in a ferrofluid emulsion.
AB  - A ferrofluid emulsion, subjected to a slowly increasing magnetic field, exhibits
      a complicated structural behavior: a gas of Brownian particles changes to
      columnar solid structures due to induced dipole interaction. Two transition
      (intermediate) structural regimes are observed: (i) randomly distributed chains
      and particles and (ii) distinct thin columns and randomly distributed chains and
      particles. Three structural transition magnetic fields are found, one marking
      each structural transition, from the initial to the final structural regime. A
      structural diagram of the structural transition magnetic fields, H(C), versus
      particle volume fractions, straight phi, is constructed experimentally.
      Theoretical models of scaling calculations, based upon the dominant magnetic
      interaction in each structural regime, give the three structural transition
      magnetic-field relations as H(C1) proportional to straight phi(-1/2), H(C2)
      proportional to straight phi(-1/4), and H(C3) proportional to (straight
      phi(gamma)/G2)exp(piG/straight phi((gamma/2))), where gamma=0.39 and G=0.29 for
      our sample. The final end shape of columns and the relative position between
      columns show that the end-end repulsion between chains is important in the
      structural formation.

PMID- 11304257
TI  - Thermal conductance and wettability of xenon on resorcinol-formaldehyde aerogels.
AB  - We have performed thermal conductivity and adsorption isotherm measurements to
      investigate the system formed by Xe adsorbed on resorcinol-formaldehyde (RF)
      aerogel. Below 80 K, the thermal conductivity of the Xe/RF-aerogel system is
      essentially identical to that of the bare RF aerogel; however, above this
      temperature the thermal conductivity of the system increases significantly above
      that of the bare aerogel. Adsorption isotherm measurements indicate that Xe
      incompletely wets the RF aerogel below Xe's bulk triple point temperature. The
      thickness of the Xe film that forms on the RF aerogel decreases with decreasing
      temperature. By 80 K the total amount of Xe present on the aerogel in equilibrium
      with the saturated vapor pressure is less than the amount needed to form about
      1.5 atomic layers of Xe on the substrate. We attribute the observed changes in
      the thermal conductivity of the Xe/aerogel system to changes in the wettability
      of the aerogel by the Xe film.

PMID- 11304258
TI  - Fluctuations and ordering in macroion suspensions.
AB  - We calculate the static properties of macroion density fluctuations in both bulk
      and in confined, strongly interacting, macroion suspensions (macroions interact
      via the Derjaguin-Landau-Verwey-Overbeek potential) in terms of a simple density
      functional ansatz. We show how to map a strongly interacting suspension to a
      weakly interacting one and obtain the renormalized charge, diameter and
      scattering structure factors analytically. The model is extrapolated to predict
      crystalline order in terms of a Hansen-Verlet-type of criterion as well as an
      effective hard-sphere crystallization condition, and good agreement with
      simulations is found. The increase in correlations observed in recent experiments
      in two, confined layers is demonstrated.

PMID- 11304259
TI  - Thermal chain model of electrorheology and magnetorheology.
AB  - Steady shear simulations of electrorheology (ER) and magnetorheology (MR) in a
      uniaxial field are presented. These large scale simulations are three
      dimensional, and include the effect of Brownian motion. In the absence of thermal
      fluctuations, the expected shear thinning viscosity is observed and a striped
      phase is seen to rapidly form in a uniaxial field, with a shear slip zone in each
      sheet. However, as the influence of Brownian motion increases, the fluid stress
      decreases, especially at lower Mason numbers, and the striped phase eventually
      disappears, even when the fluid stress is still high. To account for the uniaxial
      steady shear data we propose a microscopic chain model of the role played by
      thermal fluctuations on the rheology of ER and MR fluids that delineates the
      regimes where an applied field can impact the fluid viscosity, and gives an
      analytical prediction for the thermal effect.

PMID- 11304262
TI  - Volume-term theories of phase separation in colloidal systems and long-range
      attractive tail in the pair potential between colloidal particles.
AB  - To explain the experimental observation that colloidal dispersion exhibits a "two
      state" structure under certain conditions, Sogami and Ise (SI) proposed a model
      for an "effective" pair potential between colloidal particles which had an
      "attractive tail" more than a decade ago. The SI paper spawned several papers
      that dwelled on the shortcoming of the SI paper or strived to provide other
      explanations for the observed inhomogeneity of the suspension. We show herein
      that a long range attraction in the pair potential between colloidal particles is
      also obtained in "volume-term" theories in which the repulsive DLVO potential is
      retained.

PMID- 11304263
TI  - Rotational dynamics of magnetic particles in suspensions.
AB  - An approach for the rotational dynamics of magnetic particles and their magnetic
      moments, in fluid suspensions, is developed. A possible application is to
      magnetic resonance in ferrofluids. Based on a generalized Lagrangian formulation
      for the equations of motion of the particle, we introduce its interaction with
      the solvent fluid via dissipative and random noise torques, as well as the
      interaction between the particle and its magnetic moment, treated as an
      independent physical entity and characterized by three generalized coordinates:
      its two polar angles and its modulus. In the appropriate limits, it reduces to
      the cases of superparamagnetic particles or nonsuperparamagnetic (blocked
      magnetic moments) particles. It is also indicated how the dynamic complex
      susceptibility may be calculated from the equations of motion, and as an example
      the effect of the particles inertia on the susceptibility is numerically
      evaluated for some arbitrary values of the parameters.

PMID- 11304264
TI  - Metastable state dynamics and power law relaxation in a supercooled liquid.
AB  - We consider glassy relaxation by using a model for supercooled liquid where the
      usual set of hydrodynamic variables is extended to include the presence of very
      slowly decaying defect densities. The long time limit of the density correlation
      function, the nonergodicity parameter, is studied in the vicinity of the dynamic
      transition point, and scaling exponents with respect to the distance from the
      critical point are obtained. In addition to the usual square root cusp, we also
      see a linear dependence on distance from transition with respect to the
      metastability parameters. We analyze the power law relaxation of the density
      correlation function at the initial stage of the dynamics, and obtain an exponent
      dependent on temperature. Results are compared with data obtained from light
      scattering experiments.

PMID- 11304265
TI  - Monte Carlo simulations of polymer brushes.
AB  - Three-dimensional Monte Carlo simulations of flexible and semiflexible polymer
      brushes at various grafting densities are carried out to study their equilibrium
      structure and attendant properties by using the bond fluctuation model. Our
      simulation results of long flexible polymer brushes are, in general, consistent
      with predictions of the self-consistent field theory. However, a depletion layer
      near the substrate is only observed at small grafting densities but not at medium
      densities. We have also measured the brush height and end-to-end distance of
      various polymer brushes, and their dependence on grafting density, chain length,
      and chain stiffness are obtained. The distribution of bending angles at various
      temperatures are calculated for four different forms of bending energy and our
      simulation results agree with theoretical predictions very well. Moreover, we
      study the isotropic-to-nematic transition of polymer brushes, which is found to
      be a continuous phase transition from our simulation results. Finally, we discuss
      the effects of local grafting density fluctuation on the monomer and end density
      distributions.

PMID- 11304266
TI  - Dipole orientational order at the critical interface.
AB  - We present experimental evidence that dipoles exhibit orientational order at the
      critical interface of mixtures of polar plus nonpolar liquids using the technique
      of ellipsometry. In this technique the ellipticity rho; at the critical interface
      for all nonpolar or weakly polar fluids or fluid mixtures diverges as t(beta-nu)
      where t=(Tc-T)/Tc is the reduced temperature relative to the critical temperature
      Tc and beta=0.328, nu=0.632 are critical exponents. For polar fluids, however,
      the dipole-image dipole interaction at the interface can cause long-range
      orientational order resulting in deviations from this power-law divergence.
      Theoretical results predict that the surface orientational order parameter
      alpha2(z) approximately m(*4)[d2v(z)/dz2], where m(*) is the reduced dipole
      moment and v(z) is the local composition at position z within the interface. We
      find quantitative agreement with these predictions for two different critical
      binary liquid mixtures composed of a highly polar plus nonpolar component.

PMID- 11304268
TI  - Charge heteroaggregation between hard and soft particles.
AB  - In this paper, the heteroaggregation of opposite sign hard and soft colloidal
      particles has been studied by static and dynamic light scattering. The structure
      of the aggregates, as well as the aggregation kinetics, have been investigated.
      At low electrolyte concentration, where both long-range electrostatic repulsive
      and attractive forces are present, the aggregates were found to be more open than
      expected for diffusion-limited cluster aggregation (DLCA). However, the aggregate
      size time evolution is characteristic of diffusion-controlled processes. At high
      electrolyte concentration, where DLCA would be expected, very compacted clusters
      were found, as well as very rapid aggregation, leading to high polydispersity.
      These latter findings are interpreted in terms of the differences in the
      homoaggregation speeds for the hard and soft particles.

PMID- 11304269
TI  - Critical dynamics of gelation.
AB  - Shear relaxation and dynamic density fluctuations are studied within a Rouse
      model, generalized to include the effects of permanent random crosslinks. We
      derive an exact correspondence between the static shear viscosity and the
      resistance of a random resistor network. This relation allows us to compute the
      static shear viscosity exactly for uncorrelated crosslinks. For more general
      percolation models, which are amenable to a scaling description, it yields the
      scaling relation k=straight phi-beta for the critical exponent of the shear
      viscosity. Here beta is the thermal exponent for the gel fraction, and straight
      phi is the crossover exponent of the resistor network. The results on the shear
      viscosity are also used in deriving upper and lower bounds on the incoherent
      scattering function in the long-time limit, thereby corroborating previous
      results.

PMID- 11304270
TI  - Contact-angle hysteresis in solid-on-solid wetting.
AB  - The spreading of an elastic adhesive sphere on a substrate is calculated using
      continuum elasticity theory and the van der Waals interaction between the solid
      surfaces. The deformation and contact area are obtained self-consistently as a
      function of load. Hysteresis is demonstrated between the loading and the
      unloading cycles: the receding contact angle exceeds the advancing one. In
      addition, for a given deformation (flattening), or for a given applied load, the
      receding contact area exceeds the advancing one. This nonequilibrium phenomenon
      is velocity dependent and in accord with experiments on adhesion and crack
      propagation.

PMID- 11304272
TI  - Nematic director slippage: role of the angular momentum of light.
AB  - We propose a theoretical model of the light-induced director slippage effect. In
      this effect the bulk director reorientation contributes to the surface director
      reorientation. It is found that the director and ellipticity profiles, obtained
      in the geometric optics approximation, are dependent on the ellipticity of the
      incident light wave. The director distribution is spatially modulated in linearly
      polarized light but grows monotonically in circularly polarized light. The
      surface director deviation has been examined, and comparison made with existing
      experimental data, which then permits the magnitude of the orientational
      nonlinearity coefficient to be calculated.

PMID- 11304273
TI  - Second-harmonic generation studies in the B2 and B4 phases of a banana-shaped
      liquid crystal.
AB  - Second-harmonic generation (SHG) measurements have been performed in the B2 phase
      of the achiral banana-shaped molecule with n=12 alkoxy end chains (P-12-O-PIMB).
      A quantitative value of the nonlinear efficiency has been obtained from SHG
      curves at oblique incidences, taking into account that the signal is generated by
      a random orientation of different domains. In the B4 phase, circular dichroism,
      optical absorption and SHG studies have been carried out. It has been found that
      there are no simple helical arrangements giving rise to selective reflection in
      the visible region of the spectrum. In addition, some unusual features of the SHG
      behavior are pointed out. It is concluded that the phase is intrinsically
      inactive for the SHG process. The detected signal is due to the presence of some
      birefringent inclusions that are created at the B2 to B4 transition and slowly
      disappear while the sample is maintained within the B4 phase. A structural model
      for these inclusions is presented.

PMID- 11304274
TI  - Acoustic wave propagation in structurally helical media.
AB  - A theoretical analysis is given of the acoustic wave propagation in periodically
      nonhomogeneous media made of a solid material whose stiffness tensor is uniformly
      rotating along a given axis. In the last years, such media have been studied
      theoretically as well as experimentally, in particular for what concerns sample
      preparation and possible applications. A detailed analysis of their acoustical
      properties is given here, based on fully analytic and simple propagation
      equations. For axial propagation: (i) the dispersion curves of media where the
      transversal field components and the longitudinal ones are not coupled show only
      one forbidden band, that gives selective Bragg diffraction; in the opposite case
      they show at least a second forbidden band, that involves the quasilongitudinal
      and one of the quasitransversal eigenmodes; (ii) in the first case (absence of
      coupling), the medium gives pure acoustical rotation for p<<lambda, where p is
      the helical pitch and lambda the acoustical wavelength, a nonperfectly uniform
      but very large rotatory power for p of the order of lambda, and a guided rotation
      for p>>lambda; (iii) in the presence of the coupling, regions of mode exchange
      between the longitudinal component and a transversal one are generally present.
      The cases of lossy media and of quasiaxial propagation are also considered, and
      the analogies between optical and acoustical properties discussed.

PMID- 11304275
TI  - Rotational viscosity, dynamic phenomena, and dielectric properties in a long
      chain liquid crystal: NMR study and theoretical treatment.
AB  - The rotational diffusion constants D(perpendicular) and D(parallel), rotational
      viscosity coefficients gamma(i) (i=1,2), the orientational correlation times
      tau(L)mn, and the dielectric permittivities for nematic liquid crystals (NLCs)
      are investigated. gamma(i) are calculated by a combination of existing
      statistical-mechanical approach (SMA) and NMR relaxation theory, both based on a
      rotational diffusion model. In the rotational diffusion model, it is assumed that
      the reorientation of an individual molecule is a stochastic Brownian motion in a
      certain potential of mean torque. According to the SMA, gamma(i) are found to be
      a function of temperature, density, rotational diffusion constant for tumbling
      motions, and the orientational order parameters. The order parameters and
      rotational diffusion constant are obtained from an analysis of NMR measurements.
      Reasonable agreement between the calculated and experimental values of gamma(i)
      for 4-n-octyloxy-4'-cyanobiphenyl (8OCB) is obtained. The orientational
      correlation times, and the longitudinal and transverse components of the real
      chi'(j)(omega) and imaginary chi"(j)(omega) (j= parallel, perpendicular) parts of
      the complex susceptibility tensor for 8OCB molecules in the nematic phase are
      also obtained.

PMID- 11304276
TI  - Optically induced periodic structures in smectic-C liquid crystals.
AB  - We explore periodic structures of smectic-C (SmC) liquid crystals, induced
      optically by a polarization grating. The studied cells contain a passive surface
      of rubbed polyimide and an active photosensitive substrate of azo-dye doped
      polyimide. In a nematic phase the director field can be periodic independent of
      the angle between the grating vector and the rubbing direction. In the SmA phase
      periodic structure can be induced only by layer undulations. The SmC behaves
      similarly to the nematic phase, but the director can rotate only on a cone, which
      results in a more complex geometry. The periodic pattern is superimposed with
      four different director and layer structures. In spite of the coexistence of the
      nonuniform structures the diffraction efficiency is better in the SmC, than in
      the nematic phase.

PMID- 11304277
TI  - Molecular dynamics study of mesophase formation using a transverse quadrupolar
      Gay-Berne model.
AB  - The effect of the transverse electric quadrupole moment on the formation of
      liquid-crystal mesophases was investigated by means of a computer-simulation
      study. A simple model of the molecular interaction employed the addition of a
      transverse, point quadrupole to a Gay-Berne potential. The transverse quadrupole
      was seen to raise the temperature of onset of the smectic phase. A large
      magnitude quadrupole stabilized the smectic-A phase over the temperature range
      studied compared to a Gay-Berne reference fluid. The presence of a large
      quadrupole stabilized cubic smectic phases rather than the more usual hexagonal
      smectic-B phases.

PMID- 11304278
TI  - Experimental NMR spin-lattice relaxometry study in the liquid crystalline nematic
      phase of propylcyano-phenylcyclohexane.
AB  - The NMR spin-lattice proton relaxation dispersion T1(nu(L)) of the liquid crystal
      propylcyano-phenylcyclohexane is studied over several decades of Larmor
      frequencies and at different temperatures in the nematic mesophase. The results
      show that the order fluctuation of the local nematic director contribution to
      T1(nu(L)) undergoes a transition between two power regimes: from T1(nu(L))
      protional to nu(1/2)L to nu(alpha)L (alpha approximately 1/3) on going from low
      to high Larmor frequencies.

PMID- 11304279
TI  - Numerical bifurcation study of electrohydrodynamic convection in nematic liquid
      crystals.
AB  - We present the results of a numerical investigation of the Ericksen-Leslie
      equations for the problem of electrohydrodynamic convection in a nematic liquid
      crystal. The combination of a finite element approach and numerical bifurcation
      techniques allows us to provide details of the basic flow and include the
      physically relevant effect of nonslip side walls. We are also able to include
      material properties as parameters and this permits us to draw comparisons with
      available experimental data. We then compare and contrast the bifurcation
      structure with that of Rayleigh-Benard and Taylor-Couette flows and explore the
      role of symmetries by including a fringing electric field.

PMID- 11304280
TI  - Polymer dynamics in time-dependent Matheron-de Marsily flows: an exactly solvable
      model.
AB  - We introduce a model of random layered media, extending the Matheron-de Marsily
      model: Here we allow for the flows to change in time. For such layered
      structures, we solve exactly the equations of motion for single particles and
      also for polymers modelled as Rouse chains. The results show a rich variety of
      dynamical patterns.

PMID- 11304281
TI  - Local interaction simulation approach for the response of the vascular system to
      metabolic changes of cell behavior.
AB  - The self-regulatory interactions between cells and the vascular system are
      mediated by signals propagating at a finite speed. In order to build up a
      physical model of these processes, several features, such as storing of internal
      energy, nonclassical nonlinear behavior, and delay and threshold effects, have to
      be taken into account. Considering cells as particles in different metabolic
      states according to their internal energy, we have developed a model based on the
      local interaction simulation approach. Several numerical results, in qualitative
      agreement with biological observations, illustrate the applicability of the model
      and the method to implement it.

PMID- 11304282
TI  - Dynamics of a bouncing ball in human performance.
AB  - On the basis of a modified bouncing-ball model, we investigated whether human
      movements utilize principles of dynamic stability in their performance of a
      similar movement task. Stability analyses of the model provided predictions about
      conditions indicative of a dynamically stable period-one regime. In a series of
      experiments, human subjects bounced a ball rhythmically on a racket and displayed
      these conditions supporting that they attuned to and exploited the dynamic
      stability properties of the task.

PMID- 11304283
TI  - Correlation property of length sequences based on global structure of the
      complete genome.
AB  - This paper considers three kinds of length sequences of the complete genome.
      Detrended fluctuation analysis, spectral analysis, and the mean distance spanned
      within time L are used to discuss the correlation property of these sequences.
      The values of the exponents from these methods of these three kinds of length
      sequences of bacteria indicate that the long-range correlations exist in most of
      these sequences. The correlations have a rich variety of behaviors including the
      presence of anti-correlations. Furthermore, using the exponent gamma, it is found
      that these correlations are all linear (gamma=1.0+/-0.03). It is also found that
      these sequences exhibit 1/f noise in some interval of frequency (f>1). The length
      of this interval of frequency depends on the length of the sequence. The shape of
      the periodogram in f>1 exhibits some periodicity. The period seems to depend on
      the length and the complexity of the length sequence.

PMID- 11304284
TI  - Stability of neuronal pulses composed of concatenated unstable kinks.
AB  - We demonstrate that a traveling pulse solution, emerging from the concatenation
      of two unstable kinks, can be stable. By means of stability analysis and
      numerical simulations, we show the stability of neuronal pulses (action
      potentials) with increasing refractory periods, which decompose into two
      (radiationally) unstable kinks in the limit. These action potentials are
      solutions of an ultrarefractory version of the FitzHugh-Nagumo system.

PMID- 11304285
TI  - Multivariate Ornstein-Uhlenbeck processes with mean-field dependent coefficients:
      application to postural sway.
AB  - We study the transient and stationary behavior of many-particle systems in terms
      of multivariate Ornstein-Uhlenbeck processes with friction and diffusion
      coefficients that depend nonlinearly on process mean fields. Mean-field
      approximations of this kind of system are derived in terms of Fokker-Planck
      equations. In such systems, multiple stationary solutions as well as bifurcations
      of stationary solutions may occur. In addition, strictly monotonically decreasing
      steady-state autocorrelation functions that decay faster than exponential
      functions are found, which are used to describe the erratic motion of the center
      of pressure during quiet standing.

PMID- 11304286
TI  - Extinction of a bacterial colony under forced convection in pie geometry.
AB  - The extinction of a bacterial colony, as it is forced to migrate into a hostile
      environment, is analyzed in pie geometry. Under convection, separation of the
      radial and the azimuthal degrees of freedom is not possible, so the linearized
      evolution operator is diagonalized numerically. Some characteristic scales are
      compared with the results of recent experiments, and the "integrable" limit of
      the theory in the narrow growth region is studied.

PMID- 11304288
TI  - Simulation of enzymatic cellular reactions complicated by phase separation.
AB  - We present two-dimensional Monte Carlo simulations of enzymatic cellular reaction
      occurring via the Michaelis-Menten scheme in the case of attractive interactions
      between the reaction products. The model employed predicts phase separation in
      the cell provided that the reaction is relatively fast. The shape of the
      corresponding patterns varies from a few separate islands to a large patch
      located in the center of the cell. The fluctuations of the reaction rate during
      such regimes are found to be much higher than those predicted by the Poissonian
      distribution.

PMID- 11304287
TI  - Method for obtaining structure and interactions from oriented lipid bilayers.
AB  - Precise calculations are made of the scattering intensity I(q) from an oriented
      stack of lipid bilayers using a realistic model of fluctuations. The quantities
      of interest include the bilayer bending modulus Kc, the interbilayer interaction
      modulus B, and bilayer structure through the form factor F(qz). It is shown how
      Kc and B may be obtained from data at large q(z) where fluctuations dominate.
      Good estimates of F(qz) can be made over wide ranges of q(z) by using I(q) in q
      regions away from the peaks and for q(r) not equal0 where details of the
      scattering domains play little role. Rough estimates of domain sizes can also be
      made from smaller q(z) data. Results are presented for data taken on fully
      hydrated, oriented DOPC bilayers in the L(alpha) phase. These results illustrate
      the advantages of oriented samples compared to powder samples.

PMID- 11304289
TI  - Stochastic gene expression: density of defects frozen into permanent Turing
      patterns.
AB  - We estimate density of defects frozen into a biological Turing pattern which was
      turned on at a finite rate. Self-locking of gene expression in individual cells,
      which makes the Turing transition discontinuous, stabilizes the pattern together
      with its defects. Defects frozen into the pattern are a permanent record of the
      transition-they give an animal its own characteristic lifelong "fingerprints" or,
      as for vital organ formation, they can be fatal. Density of defects scales like
      the fourth root of the transition rate. This dependence is so weak that there is
      not enough time during morphogenesis to get rid of defects simply by slowing down
      the rate. A defect-free pattern can be obtained by spatially inhomogeneous
      activation of the genes. If the supercritical density of activator spreads slower
      than certain threshold velocity, then the Turing pattern is expressed without any
      defects.

PMID- 11304290
TI  - Representational capacity of a set of independent neurons.
AB  - The capacity with which a system of independent neuron-like units represents a
      given set of stimuli is studied by calculating the mutual information between the
      stimuli and the neural responses. Both discrete noiseless and continuous noisy
      neurons are analyzed. In both cases, the information grows monotonically with the
      number of neurons considered. Under the assumption that neurons are independent,
      the mutual information rises linearly from zero, and approaches exponentially its
      maximum value. We find the dependence of the initial slope on the number of
      stimuli and on the sparseness of the representation.

PMID- 11304291
TI  - Group selection models in prebiotic evolution.
AB  - The evolution of enzyme production is studied analytically using ideas of the
      group selection theory for the evolution of altruistic behavior. In particular,
      we argue that the mathematical formulation of Wilson's structured deme model [The
      Evolution of Populations and Communities (Benjamin-Cumings, Menlo Park, 1980)] is
      a mean-field approach in which the actual environment that a particular
      individual experiences is replaced by an average environment. That formalism is
      further developed so as to avoid the mean-field approximation and then applied to
      the problem of enzyme production in the prebiotic context, where the enzyme
      producer molecules play the altruists role while the molecules that benefit from
      the catalyst without paying its production cost play the nonaltruists role. The
      effects of synergism (i.e., division of labor) as well as of mutations are also
      considered and the results of the equilibrium analysis are summarized in phase
      diagrams showing the regions of the space of parameters where the altruistic,
      nonaltruistic, and the coexistence regimes are stable. In general, those regions
      are delimitated by discontinuous transition lines which end at critical points.

PMID- 11304294
TI  - Molecular switching with nonexponential relaxation patterns: a random walk
      approach.
AB  - The transition from an initial, locally stable configuration to a globally stable
      state in molecular switches is investigated in terms of a random walk model,
      effectively taking the reaction pathway through a potentially rugged energy
      landscape into account. Exponential and nonexponential scenarios are discussed
      and the implications on measurable quantities are explored.

PMID- 11304296
TI  - Diffusive mass transfer by nonequilibrium fluctuations: Fick's law revisited.
AB  - Recent experimental and theoretical works have shown that giant fluctuations are
      present during diffusion in liquid systems. We use linearized fluctuating
      hydrodynamics to calculate the net mass transfer due to these nonequilibrium
      fluctuations. Remarkably, the mass flow turns out to coincide with the usual
      Fick's one. The renormalization of the hydrodynamic equations allows us to
      quantify the gravitational modifications of the diffusion coefficient induced by
      the gravitational stabilization of long wavelength fluctuations.

PMID- 11304297
TI  - Effect of incompressibility on lateral instabilities of polymer brushes in a poor
      solvent.
AB  - We report a theoretical investigation of the lateral instability of grafted
      polymer layers in a poor solvent. Within self-consistent mean-field theory, we
      carry out a linear stability analysis at the random phase approximation level,
      for which an explicit incompressibility condition is enforced. Our analysis
      predicts a stability diagram in which regions of stable and unstable polymer
      brush profiles are located. Compared with analysis where incompressibility is not
      taken into account, our results suggest that lateral stability is enhanced.

PMID- 11304298
TI  - Frost heave in physisorbed films: vapor flow and substrate effects.
AB  - The magnitude of vapor flow accompanying the surface-melted liquid flow in
      physisorbed multilayer films due to thermomolecular pressures was estimated. It
      was found that the vapor flow is significant compared to the flow of the surface
      melted liquid in thick films. As the flows continue, the film thickness profile
      evolves into one determined by a dynamic equilibrium of vapor pressure. The flow
      of surface-melted liquid stops when the dynamic equilibrium is reached.

PMID- 11304299
TI  - Fluctuation-dissipation relation in a sheared fluid.
AB  - In a fluid out of equilibrium, the fluctuation-dissipation theorem (FDT) is
      usually violated. Using molecular dynamics simulations, we study in detail the
      relationship between correlation and response functions in a fluid driven into a
      stationary nonequilibrium state. Both the high temperature fluid state and the
      low temperature glassy state are investigated. In the glassy state, the violation
      of the FDT is similar to the one observed previously in an aging system in the
      absence of external drive. In the fluid state, violations of the FDT appear only
      when the fluid is driven beyond the linear response regime, and are then similar
      to those observed in the glassy state. These results are consistent with the
      picture obtained earlier from theoretical studies of driven mean-field disordered
      models, confirming the similarity between these models and simple glassy systems.

PMID- 11304300
TI  - Nonlinear model for Marangoni convection.
AB  - We have constructed a Lorenz-like model for Marangoni convection with finite wave
      number in large aspect ratio situations. Within the model, there is exchange of
      stabilities at the onset of convection and beyond the onset there is onset of
      oscillations due to the presence of surface fluctuations. The oscillations become
      chaotic as the Marangoni number is increased.

PMID- 11304301
TI  - Comment on "theory for the bending anisotropy of lipid membranes and tubule
      formation".
AB  - We point out that the mechanism proposed by Chen [Phys. Rev. E 59, 6192 (1999)]
      for the stabilization of tubular vesicles via bending anisotropy and edge tension
      cannot be applied to symmetric bilayers. Other possible mechanisms are reviewed,
      with special emphasis on one involving a nematic order of the surfactant polar
      heads.

PMID- 11304303
TI  - Local-spin-density-approximation molecular-dynamics simulations of dense
      deuterium.
AB  - Local-spin-density-approximation molecular-dynamics simulations of deuterium in
      the dissociating regime are presented, with a particular emphasis on the
      molecular phase of two isochores corresponding for deuterium to V=6 cm(3)/mole,
      rho=0.670 g/cm(3) and V=4 cm(3)/mole, rho=1 g/cm(3). It is shown that the
      transition from the molecular regime, well described by the local-spin-density
      approximation functional, to the dissociated regime where previous local-density
      approximation results are recovered, comes with a negative curvature
      deltaP/deltaT<0 in the isochore. We show that this effect is not enough to
      explain the large compressibility measured in the laser experiments [L. B.
      DaSilva et al., Phys. Rev. Lett. 78, 483 (1997); G. W. Collins et al., Science
      281, 1178 (1998); P. Celliers et al., Phys. Rev. Lett. 84, 5564 (2000)].

PMID- 11304304
TI  - Passive scalar turbulence in high dimensions.
AB  - Exploiting a Lagrangian strategy we present a numerical study for both
      perturbative and nonperturbative regions of the Kraichnan advection model. The
      major result is the numerical assessment of the first-order 1/d expansion by
      Chertkov, Falkovich, Kolokolov, and Lebedev [Phys. Rev. E 52, 4924 (1995)] for
      the fourth-order scalar structure function in the limit of high dimension d's. In
      addition to the perturbative results, the behavior of the anomaly for the sixth
      order structure functions versus the velocity scaling exponent, xi, is
      investigated and the resulting behavior is discussed.

PMID- 11304305
TI  - Effect of sidewall conductance on heat-transport measurements for turbulent
      Rayleigh-Benard convection.
AB  - For measurements of turbulent heat transport in Rayleigh-Benard convection the
      correction for the sidewall conductance is usually neglected or based on
      measurements or estimates for the empty cell. It is argued that the lateral
      thermal coupling between the fluid and the wall can invalidate these approaches,
      and that corrections based on calculations of the two-dimensional temperature
      fields are required in some cases. These corrections can increase gamma obtained
      from fits of N=N(0)Rgamma (R is the Rayleigh number) to the Nusselt number N(R)
      by 0.02 or more, yielding values in the range 0.30 to 0.33, which are larger than
      most theoretical predictions.

PMID- 11304306
TI  - Renormalized expression for the turbulent energy dissipation rate.
AB  - Conditional elimination of degrees of freedom is shown to lead to an exact
      expression for the rate of turbulent energy dissipation in terms of a
      renormalized viscosity and a correction. The correction is neglected on the basis
      of a previous hypothesis [W. D. McComb and C. Johnston, J. Phys. A 33, L15
      (2000)] that there is a range of parameters for which a quasistochastic estimate
      is a good approximation to the exact conditional average. This hypothesis was
      tested by a perturbative calculation to second order in the local Reynolds
      number, and the Kolmogorov prefactor (taken as a measure of the renormalized
      dissipation rate) was found to reach a fixed point which was insensitive to
      initial values of the kinematic viscosity and to values of the spatial rescaling
      factor h in the range 0.4< or =h< or =0.8.

PMID- 11304307
TI  - Investigation of a hydrogen plasma waveguide.
AB  - A hydrogen plasma waveguide for high-intensity laser pulses is described. The
      guiding channel is formed by a small-scale discharge in a hydrogen-filled
      capillary. The measured lifetime of the capillary is inferred to be greater than
      10(6) shots. The results of interferometric measurements of the electron density
      in the capillary are presented. The guiding channel is found to be highly ionized
      with an axial electron density of 2.7x10(18) cm(-3), and parabolic, the curvature
      corresponding to a matched spot-size of 37.5 microm.

PMID- 11304308
TI  - Realistic spin glasses below eight dimensions: A highly disordered view.
AB  - By connecting realistic spin glass models at low temperature to the highly
      disordered model at zero temperature, we argue that ordinary Edwards-Anderson
      spin glasses below eight dimensions have at most a single pair of physically
      relevant pure states at nonzero low temperature. Less likely scenarios that evade
      this conclusion are also discussed.

PMID- 11304309
TI  - Heuristic derivation of continuum kinetic equations from microscopic dynamics.
AB  - We present an approximate and heuristic scheme for the derivation of continuum
      kinetic equations from microscopic dynamics for stochastic, interacting systems.
      The method consists of a mean-field-type, decoupled approximation of the master
      equation followed by the "naive" continuum limit. The Ising model and driven
      diffusive systems are used as illustrations. The equations derived are in
      agreement with other approaches, and consequences of the microscopic dependences
      of coarse-grained parameters compare favorably with exact or high-temperature
      expansions. The method is valuable when more systematic and rigorous approaches
      fail, and when microscopic inputs in the continuum theory are desirable.

PMID- 11304310
TI  - Universal amplitude ratios of the renormalization group: two-dimensional
      tricritical Ising model.
AB  - The scaling form of the free energy near a critical point allows for the
      definition of various thermodynamical amplitudes and the determination of their
      dependence on the microscopic nonuniversal scales. Universal quantities can be
      obtained by considering special combinations of the amplitudes. Together with the
      critical exponents they characterize the universality classes and may be useful
      quantities for their experimental identification. We compute the universal
      amplitude ratios for the tricritical Ising model in two dimensions by using
      several theoretical methods from perturbed conformal field theory and scattering
      integrable quantum field theory. The theoretical approaches are further supported
      and integrated by results coming from a numerical determination of the energy
      eigenvalues and eigenvectors of off-critical systems in an infinite cylinder.

PMID- 11304311
TI  - Driven electron transfer in an environment with slow and fast degrees of freedom.
AB  - Driven electron transfer in a polar medium with slow and fast degrees of freedom
      is studied in the framework of a spin-boson Hamiltonian. Evolution dynamics is
      rigorously found when omega(s)(c)/(Gamma(a))sqrt[E(rs)/kT]<<1, where omega(s)(c)
      is the Debye cutoff frequency in the spectral function for the slow modes, E(rs)
      is the reorganization energy of slow degrees of freedom, and Gamma(-1)(a) is the
      reaction time dependent on the laser intensity parameter a=muE(0)/Planck's over
      2piomega. Here omega and E0 are the frequency and the amplitude of a cw electric
      field, and mu is the electron dipole moment difference between the initial and
      final states. The master equation is derived for an arbitrary driving force
      affecting both the transition matrix element and the potential energy. For a cw
      electric field, the time dependent probability of staying at the product state,
      P1(t), is shown to be strongly dependent on the field intensity parameter a:
      P1(a,t) approximately (Gamma(m(1),m(2))t)(-E(rf)/E(rs)) or P1(a,t) approximately
      (Gamma(m(0))t)(-E(rf)/E(rs)), double or single resonances, respectively. Here
      E(rf) is the reorganization energy of fast degrees of freedom, Gamma(m(1),m(2))
      approximately J(2)(m(1))(a)+J(2)(m(2))(a), and Gamma(m(0)) approximately
      J(2)(m(0))(a), where J(a) is a Bessel function. By changing the parameter a, one
      is able to manipulate the rate and direction of the reaction. When J(2)(m(0))(a)
      is close to zero the reaction is slow. Hence, slow modes turn out to be fast.
      This changes the character of the evolution dynamics from non- to mono-
      exponential decay, respectively. For the double resonance, the equilibrium
      constant is studied with the field intensity. It is shown that the reaction is
      almost insensitive to temperature. However, it strongly depends on the reaction
      heat, which provides a condition for the resonance.

PMID- 11304312
TI  - Dynamic ultrametricity in spin glasses.
AB  - We investigate the dynamics of spin glasses from the "rheological" point of view,
      in which aging is suppressed by the action of small, nonconservative forces. The
      different features can be expressed in terms of the scaling of relaxation times
      with the magnitude of the driving force, which plays the role of the critical
      parameter. Stated in these terms, ultrametricity loses much of its mystery and
      can be checked rather easily. This approach also seems a natural starting point
      to investigate what would be the real-space structures underlying the hierarchy
      of time scales. We study in detail the appearance of this many-scale behavior in
      a mean-field model, in which dynamic ultrametricity is clearly present. A similar
      analysis is performed on numerical results obtained for a three-dimensional spin
      glass: In that case, our results are compatible with either that dynamic
      ultrametricity is absent or that it develops so slowly that even in experimental
      time-windows it is still hardly observable.

PMID- 11304313
TI  - Ground-state clusters of two-, three-, and four-dimensional +/-J Ising spin
      glasses.
AB  - A huge number of independent true ground-state configurations is calculated for
      two-, three- and four-dimensional +/-J spin-glass models. Using the genetic
      cluster-exact approximation method, system sizes up to N=20(2),8(3),6(4) spins
      are treated. A "ballistic-search" algorithm is applied, which allows even for
      large system sizes to identify clusters of ground states that are connected by
      chains of zero-energy flips of spins. The number of clusters n(C) diverges with N
      going to infinity. For all dimensions considered here, an exponential increase of
      n(C) appears to be more likely than a growth with a power of N. The number of
      different ground states is found to grow clearly exponentially with N. A zero
      temperature entropy per spin of s(0)=0.078(5)k(B) (2D), s(0)=0.051(3)k(B) (3D),
      respectively, s(0)=0.027(5)k(B) (4D) is obtained.

PMID- 11304314
TI  - Stochastic boundary conditions in the deterministic Nagel-Schreckenberg traffic
      model.
AB  - We consider open systems where cars move according to the deterministic Nagel
      Schreckenberg rules [K. Nagel and M. Schreckenberg, J. Phys. I 2, 2221 (1992)]
      and with maximum velocity v(max)>1, which is an extension of the asymmetric
      exclusion process (ASEP). It turns out that the behavior of the system is
      dominated by two features: (a) the competition between the left and the right
      boundary, (b) the development of so-called "buffers" due to the hindrance that an
      injected car feels from the front car at the beginning of the system. As a
      consequence, there is a first-order phase transition between the free flow and
      the congested phase accompanied by the collapse of the buffers, and the phase
      diagram essentially differs from that for v(max)=1 (ASEP).

PMID- 11304315
TI  - Nondeterministic Nagel-Schreckenberg traffic model with open boundary conditions.
AB  - We study the phases of the Nagel-Schreckenberg traffic model with open boundary
      conditions as a function of the randomization probabilities p>0 and the maximum
      velocity v(max)>1. Due to the existence of "buffer sites" which enhance the free
      flow region, the behavior is much richer than that of the related, parallel
      updated asymmetric exclusion process [(ASEP), v(max)=1]. Such sites exist for
      v(max)> or =3 and p<p(c) where the phase diagram is qualitatively similar to the
      p=0 case: there is a free flow and a jamming phase separated by a line of first
      order transitions. For p>p(c) an additional maximum current phase separated by
      second-order transitions occurs like for the ASEP. The density profile decays in
      the maximum current phase algebraically with an exponent gamma approximately 2 /
      3 for all v(max)> or =2 indicating that these models belong to another
      universality class than the ASEP where gamma=1 / 2.

PMID- 11304316
TI  - First-order phase transition with a logarithmic singularity in a model with
      absorbing states.
AB  - Recently, Lipowski [Phys. Rev. E 62, 4401 (2000)] investigated a stochastic
      lattice model which exhibits a discontinuous transition from an active phase into
      infinitely many absorbing states. Since the transition is accompanied by an
      apparent power-law singularity, it was conjectured that the model may combine
      features of first- and second-order phase transitions. In the present work it is
      shown that this singularity emerges as an artifact of the definition of the model
      in terms of products. Instead of a power law, we find a logarithmic singularity
      at the transition. Moreover, we generalize the model in such a way that the
      second-order phase transition becomes accessible. As expected, this transition
      belongs to the universality class of directed percolation.

PMID- 11304317
TI  - Fractal analysis of electrical trees in a cross-linked synthetic resin.
AB  - A statistical picture of dielectric breakdown in cross-linked polyester resins
      for a two-dimensional geometry is presented and discussed in this paper. A
      connection is established between the dielectric breakdown model (DBM) and the
      physical properties of the resin. Distribution propagation times of simulated
      trees obey a Weibull statistics, as was experimentally found. This adjustment is
      achieved by a redefinition of the unit of time, which is different from the one
      employed up to date. The experimental dependence of characteristic propagation
      times on the fractal dimension D can be reproduced in the range 1.2<D<1.5. A
      relationship is established between the glass transition temperature T(g) and the
      DBM parameter eta, which is in agreement with thermodynamical considerations. It
      is suggested that fractal characteristics of electrical trees should be related
      to a basic material property, such as the cross-linking density, which implies a
      notion of universality that deserves to be explored.

PMID- 11304318
TI  - Density of a gas of spin-polarized fermions in a magnetic field.
AB  - For a fermion gas with equally spaced energy levels that is subjected to a
      magnetic field, the particle density is calculated. The derivation is based on
      the path integral approach for identical particles, in combination with the
      inversion techniques for the generating function of the static response
      functions. Explicit results are presented for the ground state density as a
      function of the magnetic field with a number of particles ranging from 1 to 45.

PMID- 11304319
TI  - Quantum phase transitions in the Ising model in a spatially modulated field.
AB  - The phase transitions in the transverse field Ising model in a competing
      spatially modulated (periodic and oscillatory) longitudinal field are studied
      numerically. There is a multiphase point in absence of the transverse field where
      the degeneracy for a longitudinal field of wavelength lambda is
      [(1+sqrt[5])/2](2N/lambda) for a system with N spins, an exact result obtained
      from the known result for lambda=2. The phase transitions in the Gamma
      (transverse field) versus h(0) (amplitude of the longitudinal field) phase
      diagram are obtained from the vanishing of the mass gap Delta. We find that for
      all the phase transition points obtained in this way, Delta shows finite size
      scaling behavior signifying a continuous phase transition everywhere. The values
      of the critical exponents show that the model belongs to the universality class
      of the two dimensional Ising model. The longitudinal field is found to have the
      same scaling behavior as that of the transverse field, which seems to be a unique
      feature for the competing field. The phase boundaries for two different
      wavelengths of the modulated field are obtained. Close to the multiphase point at
      h(c), the phase boundary behaves as (h(c)-h(0))(b), where b is also lambda
      dependent.

PMID- 11304320
TI  - Universality and straight phi(4) theory of finite-size effects above the upper
      critical dimension.
AB  - We analyze finite-size effects in a L(d) geometry above the upper critical
      dimension d=4 within the O(n) symmetric straight phi(4) theory on the basis of
      exact results for n-->infinity and one-loop results for n=1. We show that finite
      size effects of the straight phi(4) continuum theory with a smooth (rather than
      sharp) cutoff belong to the same universality class as those of the straight
      phi(4) lattice theory. Our analysis predicts both universal and nonuniversal
      features of finite-size effects and resolves long-standing discrepancies in
      earlier analyses of Monte Carlo (MC) data for the d=5 Ising model. Our estimates
      of two fundamental length scales xi(0) and l(0) are confirmed by very recent MC
      data.

PMID- 11304321
TI  - Phase diffusion as a model for coherent suppression of tunneling in the presence
      of noise.
AB  - We study the stabilization of coherent suppression of tunneling in a driven
      double-well system subject to random periodic delta-function "kicks." We model
      dissipation due to this stochastic process as a phase diffusion process for an
      effective two-level system, and derive a corresponding set of Bloch equations
      with phase damping terms that agree with the periodically kicked system at
      discrete times. We demonstrate that the ability of noise to localize the system
      on either side of the double-well potential arises from overdamping of the phase
      of oscillation, and not from any cooperative effect between the noise and the
      driving field. The model is investigated with a square wave drive, which has
      qualitatively similar features to the widely studied cosinusoidal drive, but has
      the additional advantage of allowing one to derive exact analytic expressions.

PMID- 11304322
TI  - Geometry of river networks. I. Scaling, fluctuations, and deviations.
AB  - This paper is the first in a series of three papers investigating the detailed
      geometry of river networks. Branching networks are a universal structure employed
      in the distribution and collection of material. Large-scale river networks mark
      an important class of two-dimensional branching networks, being not only of
      intrinsic interest but also a pervasive natural phenomenon. In the description of
      river network structure, scaling laws are uniformly observed. Reported values of
      scaling exponents vary, suggesting that no unique set of scaling exponents
      exists. To improve this current understanding of scaling in river networks and to
      provide a fuller description of branching network structure, here we report a
      theoretical and empirical study of fluctuations about and deviations from
      scaling. We examine data for continent-scale river networks such as the
      Mississippi and the Amazon and draw inspiration from a simple model of directed,
      random networks. We center our investigations on the scaling of the length of a
      subbasin's dominant stream with its area, a characterization of basin shape known
      as Hack's law. We generalize this relationship to a joint probability density,
      and provide observations and explanations of deviations from scaling. We show
      that fluctuations about scaling are substantial, and grow with system size. We
      find strong deviations from scaling at small scales which can be explained by the
      existence of a linear network structure. At intermediate scales, we find slow
      drifts in exponent values, indicating that scaling is only approximately obeyed
      and that universality remains indeterminate. At large scales, we observe a
      breakdown in scaling due to decreasing sample space and correlations with overall
      basin shape. The extent of approximate scaling is significantly restricted by
      these deviations, and will not be improved by increases in network resolution.

PMID- 11304323
TI  - Geometry of river networks. II. Distributions of component size and number.
AB  - The structure of a river network may be seen as a discrete set of nested
      subnetworks built out of individual stream segments. These network components are
      assigned an integral stream order via a hierarchical and discrete ordering
      method. Exponential relationships, known as Horton's laws, between stream order
      and ensemble-averaged quantities pertaining to network components are observed.
      We extend these observations to incorporate fluctuations and all higher moments
      by developing functional relationships between distributions. The relationships
      determined are drawn from a combination of theoretical analysis, analysis of real
      river networks including the Mississippi, Amazon, and Nile, and numerical
      simulations on a model of directed, random networks. Underlying distributions of
      stream segment lengths are identified as exponential. Combinations of these
      distributions form single-humped distributions with exponential tails, the sums
      of which are in turn shown to give power-law distributions of stream lengths.
      Distributions of basin area and stream segment frequency are also addressed. The
      calculations identify a single length scale as a measure of size fluctuations in
      network components. This article is the second in a series of three addressing
      the geometry of river networks.

PMID- 11304324
TI  - Geometry of river networks. III. Characterization of component connectivity.
AB  - Essential to understanding the overall structure of river networks is a knowledge
      of their detailed architecture. Here we explore the presence of randomness in
      river network structure and the details of its consequences. We first show that
      an averaged view of network architecture is provided by a proposed self
      similarity statement about the scaling of drainage density, a local measure of
      stream concentration. This scaling of drainage density is shown to imply
      Tokunaga's law, a description of the scaling of side branch abundance along a
      given stream, as well as a scaling law for stream lengths. We then consider
      fluctuations in drainage density and consequently the numbers of side branches.
      Data are analyzed for the Mississippi River basin and a model of random directed
      networks. Numbers of side streams are found to follow exponential distributions,
      as are intertributary distances along streams. Finally, we derive a joint
      variation of side stream abundance with stream length, affording a full
      description of fluctuations in network structure. Fluctuations in side stream
      numbers are shown to be a direct result of fluctuations in stream lengths. This
      is the last paper in a series of three on the geometry of river networks.

PMID- 11304325
TI  - Nonlinear lattice model of viscoelastic mode III fracture.
AB  - We study the effect of general nonlinear force laws in viscoelastic lattice
      models of fracture, focusing on the existence and stability of steady-state mode
      III cracks. We show that the hysteretic behavior at small driving is very
      sensitive to the smoothness of the force law. At large driving, we find a Hopf
      bifurcation to a straight crack whose velocity is periodic in time. The frequency
      of the unstable bifurcating mode depends on the smoothness of the potential, but
      is very close to an exact period-doubling instability. Slightly above the onset
      of the instability, the system settles into a exactly period-doubled state,
      presumably connected to the aforementioned bifurcation structure. We explicitly
      solve for this new state and map out its velocity-driving relation.

PMID- 11304326
TI  - Renormalization-group theoretical reduction of the Swift-Hohenberg model.
AB  - The Swift-Hohenberg model of the cellular pattern formation is exploited with a
      proto renormalization-group (RG) scheme. The method dispenses with the explicit
      perturbation solutions which are required in the standard RG approach. The RG
      equations obtained are the well-known reductive perturbation results such as a
      rotationally covariant amplitude equation and the nonlinear phase equations.

PMID- 11304327
TI  - Dynamic phase transition, universality, and finite-size scaling in the two
      dimensional kinetic Ising model in an oscillating field.
AB  - We study the two-dimensional kinetic Ising model below its equilibrium critical
      temperature, subject to a square-wave oscillating external field. We focus on the
      multidroplet regime, where the metastable phase decays through nucleation and
      growth of many droplets of the stable phase. At a critical frequency, the system
      undergoes a genuine nonequilibrium phase transition, in which the symmetry-broken
      phase corresponds to an asymmetric stationary limit cycle for the time-dependent
      magnetization. We investigate the universal aspects of this dynamic phase
      transition at various temperatures and field amplitudes via large-scale Monte
      Carlo simulations, employing finite-size scaling techniques adopted from
      equilibrium critical phenomena. The critical exponents, the fixed-point value of
      the fourth-order cumulant, and the critical order-parameter distribution all are
      consistent with the universality class of the two-dimensional equilibrium Ising
      model. We also study the cross-over from the multidroplet regime to the strong
      field regime, where the transition disappears.

PMID- 11304328
TI  - Uniaxial Hugoniostat: a method for atomistic simulations of shocked materials.
AB  - An new equilibrium molecular-dynamics method (the uniaxial Hugoniostat) is
      proposed to study the energetics and deformation structures in shocked crystals.
      This method agrees well with nonequilibrium molecular-dynamics simulations used
      to study shock-wave propagation in solids and liquids.

PMID- 11304329
TI  - Morphological image analysis of quantum motion in billiards.
AB  - Morphological image analysis is applied to the time evolution of the probability
      distribution of a quantum particle moving in two- and three-dimensional
      billiards. It is shown that the time-averaged Euler characteristic of the
      probability distribution provides a well defined quantity to distinguish between
      classically integrable and nonintegrable billiards. In three dimensions the time
      averaged mean breadth of the probability distribution may also be used for this
      purpose.

PMID- 11304330
TI  - Rotationally induced transitions in small clusters.
AB  - The dynamics of an Ar6 cluster held together by Lennard-Jones forces is studied
      classically. The development of chaotic dynamics is mainly followed by a
      calculation of the maximum Lyapunov exponent (MLE). Initial momentum vectors are
      chosen from the eigenvectors of the Hessian of the potential energy so that
      rotating and nonrotating clusters can be studied systematically. It is found that
      the dependence of MLE on the total energy is considerably different for
      rotational and vibrational excitations. As the magnitude of the angular momentum
      increases, sharp transitions in MLE are observed. These transitions are explained
      in terms of the changes of the topology of the effective rovibrational potential
      energy surface and the dynamic equilibration between the global and local minima.

PMID- 11304331
TI  - Simple variational approach to the quantum Frenkel-Kontorova model.
AB  - We present a simple and complete variational approach to the one-dimensional
      quantum Frenkel-Kontorova model. Dirac's time-dependent variational principle is
      adopted together with a Hartree-type many-body trial wave function for the atoms.
      The single-particle state is assumed to have the Jackiw-Kerman form. We obtain an
      effective classical Hamiltonian for the system, which is simple enough for a
      complete numerical solution for the static ground state of the model. Numerical
      results show that our simple approach captures the essence of the quantum effects
      first observed in quantum Monte Carlo studies.

PMID- 11304332
TI  - Dynamics and control of a multimode laser: Reduction of space-dependent rate
      equations to a low-dimensional system.
AB  - We suggest a quantitatively correct procedure for reducing the spatial degrees of
      freedom of the space-dependent rate equations of a multimode laser that describe
      the dynamics of the population inversion of the active medium and the mode
      intensities of the standing waves in the laser cavity. The key idea of that
      reduction is to take advantage of the small value of the parameter that defines
      the ratio between the population inversion decay rate and the cavity decay rate.
      We generalize the reduction procedure for the case of an intracavity frequency
      doubled laser. Frequency conversion performed by an optically nonlinear crystal
      placed inside the laser cavity may cause a pronounced instability in the laser
      performance, leading to chaotic oscillations of the output intensity. Based on
      the reduced equations, we analyze the dynamical properties of the system as well
      as the problem of stabilizing the steady state. The numerical analysis is
      performed considering the specific system of a Nd:YAG (neodymium-doped yttrium
      aluminum garnet) laser with an intracavity KTP (potassium titanyl phosphate)
      crystal.

PMID- 11304333
TI  - Electronic transport through ballistic chaotic cavities: reflection symmetry,
      direct processes, and symmetry breaking.
AB  - We extend previous studies on transport through ballistic chaotic cavities with
      spatial left-right (LR) reflection symmetry to include the presence of direct
      processes. We first analyze fully LR-symmetric systems in the presence of direct
      processes and compare the distribution w(T) of the transmission coefficient T
      with that for an asymmetric cavity with the same "optical" S matrix. We then
      study the problem of "external mixing" of the symmetry caused by an asymmetric
      coupling of the cavity to the outside. We first consider the case where symmetry
      breaking arises because two symmetrically positioned waveguides are coupled to
      the cavity by means of asymmetric tunnel barriers. Although this system is
      asymmetric with respect to the LR operation, there is an effect of the symmetry
      of the cavity it was constructed from. Second, we break LR symmetry in the
      absence of direct processes by asymmetrically positioning the two waveguides and
      compare the results with those for the completely asymmetric case.

PMID- 11304334
TI  - Covering dynamical systems: twofold covers.
AB  - We study the relation between a dynamical system, which is unchanged
      (equivariant) under a discrete symmetry group G and another locally identical
      dynamical system with no residual symmetry. We also study the converse mapping:
      lifting a dynamical system without symmetry to a multiple cover, which is
      equivariant under G. This is done in R3 for the two element rotation and
      inversion groups. Comparisons are done for the equations of motion, the strange
      attractors that they generate, and the branched manifolds that classify these
      strange attractors. A dynamical system can have many inequivalent multiple
      covers, all equivariant under the same symmetry group G. These are distinguished
      by the value of a certain topological index. Many examples are presented. A new
      global bifurcation, the "peeling bifurcation," is described.

PMID- 11304335
TI  - Constructing nonautonomous differential equations from experimental time series.
AB  - An approach to constructing model differential equations of harmonically driven
      systems is proposed. It is a modification of the standard global reconstruction
      technique: an algebraic polynomial which coefficients depend on time is used for
      approximation. Efficiency and details of the approach are demonstrated by various
      numerical and natural examples.

PMID- 11304336
TI  - Exploring phase space localization of chaotic eigenstates via parametric
      variation.
AB  - In a previous paper [Phys. Rev. Lett. 77, 4158 (1996)], a new correlation measure
      was introduced that sensitively probes phase space localization properties of
      eigenstates. It is based on a system's response to varying an external parameter.
      The measure correlates level velocities with overlap intensities between the
      eigenstates and some localized state of interest. Random matrix theory predicts
      the absence of such correlations in chaotic systems whereas in the stadium
      billiard, a paradigm of chaos, strong correlations were observed. Here, we
      develop further the theoretical basis of that work, extend the stadium results to
      the full phase space, study the Planck's over 2pi dependence, and demonstrate the
      agreement between this measure and a semiclassical theory based on homoclinic
      orbits.

PMID- 11304337
TI  - Phase space localization of chaotic eigenstates: violating ergodicity.
AB  - The correlation between level velocities and eigenfunction intensities provides a
      new way of exploring phase space localization in quantized nonintegrable systems.
      It can also serve as a measure of deviations from ergodicity due to quantum
      effects for typical observables. This paper relies on two well known paradigms of
      quantum chaos, the bakers map and the standard map, to study correlations in
      simple, yet chaotic, dynamical systems. The behaviors are dominated by the
      presence of several classical structures. These primarily include short periodic
      orbits and their homoclinic excursions. The dependences of the correlations
      deriving from perturbations allow for eigenfunction features violating ergodicity
      to be selectively highlighted. A semiclassical theory based on periodic orbit
      sums leads to certain classical correlations that are superexponentially cut off
      beyond a logarithmic time scale. The theory is seen to be quite successful in
      reproducing many of the quantum localization features.

PMID- 11304338
TI  - Logistic map with a delayed feedback: Stability of a discrete time-delay control
      of chaos.
AB  - The logistic map with a delayed feedback is studied as a generic model. The
      stability of the model and its bifurcation scheme is analyzed as a function of
      the feedback amplitude and of the delay. Stability analysis is performed
      semianalytically. A relation between the delay and the periodicity of the orbit,
      which explains why some terms used in chaos control are ineffective, was found.
      The consequences for chaos control are discussed. The structure of bifurcations
      is found to depend strongly on the parity and on the length of the delay.
      Boundary crisis, the tangent, the Neimark, as well as the period-doubling
      bifurcations occur in this system. The effective dimension of the model is also
      discussed.

PMID- 11304339
TI  - Compartmentalized reaction-diffusion systems.
AB  - Reaction-diffusion systems consisting of a collection of reactive domains
      separated by chemically inactive regions are considered. The reactive dynamics is
      governed by a multistep reaction mechanism and each reactive domain is specific
      to a particular elementary step or collection of elementary steps of the global
      reaction mechanism. Far-from-equilibrium situations where the global kinetics can
      give rise to complex states such as bistability or oscillations are studied. A
      general method for the calculation of the average concentration on each reactive
      domain is presented. The effects of compartmentalization are illustrated by a
      study of the influence of diffusion, reactive domain size, and domain
      distribution on the nature of the stationary states of the Schlogl model.
      Compartmentalization can drive the system into and out of the bistable regime of
      this reactive system.

PMID- 11304340
TI  - Synchronization, re-entry, and failure of spiral waves in a two-layer discrete
      excitable system.
AB  - A three-dimensional structure composed of two coupled discrete excitable lattices
      is considered. Each lattice (layer) is a discrete excitable subsystem and using a
      local model of excitation transfer and failure we have estimated the sufficient
      conditions for it to exhibit spiral waves. Then we show how interlayer
      synchronization of all motions is possible. Various effects of spiral wave
      synchronization, re-entry and failure are also investigated.

PMID- 11304341
TI  - Arbitrary trajectory quantization method.
AB  - The arbitrary trajectory quantization method (ATQM) is a time dependent approach
      to quasiclassical quantization based on the approximate dual relationship that
      exists between the quantum energy spectra and classical periodic orbits. It has
      recently been shown however, that, for polygonal billiards, the periodicity
      criterion must be relaxed to include closed almost-periodic (CAP) orbit families
      in this relationship. In light of this result, we reinvestigate the ATQM and show
      that at finite energies, a smoothened quasiclassical kernel corresponds to the
      modified formula that includes CAP families while the delta function kernel
      corresponding to the periodic orbit formula is recovered as E-->infinity. Several
      clarifications are also provided.

PMID- 11304342
TI  - Scattering properties of a cut-circle billiard waveguide with two conical leads.
AB  - We examine a two-dimensional electron waveguide with a cut-circle cavity and
      conical leads. By considering Wigner delay times and the Landauer-Buttiker
      conductance for this system, we probe the effects of the closed billiard energy
      spectrum on scattering properties in the limit of weakly coupled leads. We
      investigate how lead placement and cavity shape affect these conductance and time
      delay spectra of the waveguide.

PMID- 11304343
TI  - Synchronization of chaotic oscillations in doped fiber ring lasers.
AB  - The synchronization of chaotic rare-earth-doped fiber ring lasers is analyzed.
      The lasers are first coupled by transmitting a fraction c of the circulating
      electric field in the transmitter and injecting it into the optical cavity of the
      receiver. A coupling strategy which relies on modulation of the intensity of the
      light alone is also examined. Synchronization is studied as a function of the
      coupling strength, and we see excellent synchronization, even with very small c.
      We prove that in an open loop configuration (c=1) synchronization is guaranteed
      due to the particular structure of our equations and of the injection method we
      use. The generalized synchronization of these model lasers is examined when there
      is parameter mismatch between the transmitter and receiver lasers. The
      synchronization is found to be insensitive to a wide range of mismatch in laser
      parameters, but it is sensitive to other parameters, in particular those
      associated with the phase and the polarization of the circulating electric field.
      Communicating information between the transmitter and receiver lasers is also
      addressed. We investigate a scheme for modulating information onto the chaotic
      electric field and then demodulating and detecting the information embedded in
      the chaotic signal passed down the communications channel. We show full recovery
      with very low error for a wide range of coupling strengths.

PMID- 11304344
TI  - Infinite hierarchies of nonlinearly dependent periodic orbits.
AB  - Quadratic maps are used to show explicitly that the skeleton of unstable periodic
      orbits underlying classical and quantum dynamics is stratified into a doubly
      infinite hierarchy of orbits inherited from a set of basic "seeds" through
      certain nonlinear transformations T(alpha)(x). The hierarchy contains nonunique
      substructurings which arise from the different possibilities of sequencing the
      transformations T(alpha)(x). The structuring of the orbital skeleton is shown to
      be generic for Abelian equations, i.e., for all dynamical systems generated by
      iterating rational functions.

PMID- 11304345
TI  - Digital signal transmission with cascaded heterogeneous chaotic systems.
AB  - A new chaos based secure communication scheme is proposed to transmit digital
      signals by combining the concepts of chaotic-switching and chaotic-modulation
      approaches. In this scheme two heterogeneous chaotic circuits are used both at
      the transmitter and receiver modules. First a binary message signal is scrambled
      by two chaotic attractors produced by a set of chaotic systems (No. 1) of the
      drive module. The so produced small amplitude scrambled chaotic signal is further
      directly injected or modulated by different chaotic system (No. 2) within the
      drive module. Then the chaotic signal generated by this second chaotic system No.
      2 is transmitted to the response module through the channel. An appropriate
      feedback loop is constructed in the response module to achieve synchronization
      among the variables of the drive and response modules and the binary information
      signal is recovered by using the synchronization error followed by low-pass
      filtering and thresholding. Simulation results are reported in which the quality
      of the recovered signal is higher and the encoding of the information signal is
      potentially secure. The effect of perturbing factors like channel noise and
      nonidentity of parameters are also considered.

PMID- 11304346
TI  - Critical behavior of crisis-induced transition to spatiotemporal chaos in
      parameter space.
AB  - In previous works we reported a transition mechanism from a temporal chaos (TC)
      to spatiotemporal chaos (STC) through a crisis due to a collision to a saddle
      steady wave (SSW). However, the transition also displays as a critical phenomenon
      in parameter space. In the present work the time variations of mode interaction
      energy, deltaE(I)(k)(t), of the perturbation wave (PW) with its carrier SSW are
      calculated. In the TC state in all the dimensions the motion is dominated by
      negative deltaE(I)(k)(t). With variation of the parameter in one dimension
      deltaE(I)(k=1)(t) becomes smaller and smaller while statistically more balanced
      in its negative and positive values. The critical parameter point for the crisis
      is right at the place where the time-averaged negative and positive
      deltaE(I)(k=1)(t) are equal. A power-law behavior is observed when approaching to
      the point. After the crisis in the STC state the motion with positive
      deltaE(I)(k=1)(t) suddenly becomes much stronger than that with negative ones. In
      addition, it is shown that stable orbit of the SSW is a boundary of the PW
      motion, it behaves like a potential well that constrains the PW motion.

PMID- 11304347
TI  - Electrohydrodynamic instabilities and orientation of dielectric ellipsoids in low
      conducting fluids.
AB  - We study the dynamics of an ellipsoidal particle in a weakly conducting
      dielectric liquid when submitted to a dc electric field. At low field
      intensities, the particle long axis is aligned in the field direction. When the
      field strength is increased, we show that, depending on the initial orientation
      of the particle, there exist two stable orientations: the one with the long axis
      parallel to the field direction remains possible while a spinning state with the
      long axis perpendicular to the field appears. This last striking orientation is
      due to the finite Maxwell-Wagner polarization relaxation time. For sufficiently
      high field intensities, each state loses its stability and the particle dynamics
      becomes chaotic. Those conclusions from the theoretical model are supported by
      experimental observations.

PMID- 11304348
TI  - Multifractality of drop breakup in the air-blast nozzle atomization process.
AB  - The multifractal nature of drop breakup in the air-blast nozzle atomization
      process has been studied. We apply the multiplier method to extract the negative
      and the positive parts of the f(alpha) curve with the data of drop-size
      distribution measured using dual particle dynamic analyzer. A random multifractal
      model with the multiplier triangularly distributed is proposed to characterize
      the breakup of drops. The agreement of the left part of the multifractal spectra
      between the experimental result and the model is remarkable. The cause of the
      distinction of the right part of the f(alpha) curve is argued. The fact that
      negative dimensions arise in the current system means that the spatial
      distribution of the drops yielded by the high-speed jet fluctuates from sample to
      sample. In other words, the spatial concentration distribution of the disperse
      phase in the spray zone fluctuates momentarily, showing intrinsic randomness.

PMID- 11304349
TI  - Bounds on the convective heat transport in a rotating layer.
AB  - Previous bounds on the convective heat transport in a horizontal layer heated
      from below and rotating about a vertical axis have been improved through the use
      of separate energy balances for the poloidal and toroidal components of the
      velocity field. Because the additional constraint imposed for the solution of the
      variational problem for the extremalizing vector field leads to Euler-Lagrange
      equations which can no longer be solved analytically, numerical methods must be
      employed. A Galerkin scheme is introduced and the variational problem is solved
      in the case when stress-free conditions are assumed at the upper and lower
      boundaries. Results are presented as a function of the Rayleigh number and the
      rotation parameter for the Prandtl numbers P=7, 0.7, 0.1, and 0.025.

PMID- 11304350
TI  - Renormalization group analysis for thermal turbulent transport.
AB  - In this study, we continue with our previous renormalization group analysis of
      incompressible turbulence, aiming at determination of various thermal transport
      properties. In particular, the temperature field T is considered a passive
      scalar. The quasinormal approximation is assumed for the statistical correlation
      between the velocity and temperature fields. A differential argument leads to
      derivation of the turbulent Prandtl number Pr(t) as a function of the turbulent
      Peclet Pe(t) number, which in turn depends on the turbulent eddy viscosity nu(t).
      The functional relationship between Pr(t) and Pe(t) is comparable to that of
      Yakhot et al. [Int. J. Heat Mass Transf. 30, 15 (1987)] and is in close
      consistency with direct-numerical-simulation results as well as measured data
      from experiments. The study proceeds further with limiting the operation of
      renormalization group analysis, yielding an inhomogeneous ordinary differential
      equation for an invariant thermal eddy diffusivity sigma. Simplicity of the
      equation renders itself a closed-form solution of sigma as a function of the wave
      number k, which, when combined with a modified Batchelor's energy spectrum for
      the passive temperature T, facilitates determination of the Batchelor constant
      C(B) and a parallel Smagorinsky model and the model constant C(P) for thermal
      turbulent energy transport.

PMID- 11304351
TI  - Pumping of water with ac electric fields applied to asymmetric pairs of
      microelectrodes.
AB  - Bulk fluid flow induced by an ac electric potential with a peak voltage below the
      ionization potential of water is described. The potential is applied to an ionic
      solution with a planar array of electrodes arranged in pairs so that one edge of
      a large electrode is close to an opposing narrow electrode. During half the
      cycle, the double layer on the surface of the electrodes charges as current flows
      between the electrodes. The electrodes charge in a nonuniform manner producing a
      gradient in potential parallel to the surface of the electrodes. This gradient
      drives the ions in the double layer across the surface of the electrode and this
      in turn drags the fluid across the electrode surface. The anisotropic nature of
      the pairs of electrodes is used to produce a net flow of fluid. The flow produced
      is approximately uniform at a distance from the electrodes that is greater than
      the periodicity of the electrode array. The potential and frequency dependence of
      this flow is reported and compared to a simple model. This method of producing
      fluid flow differs from electrical and thermal traveling-wave techniques as only
      a low voltage is required and the electrode construction is much simpler.

PMID- 11304352
TI  - Wall-bounded turbulent shear flow: Analytic result for a universal amplitude.
AB  - In the turbulent boundary layer above a flat plate, the velocity profile is known
      to have the form v=v(0)[(1/kappa)ln z+const]. The distance from the wall in
      dimensionless units is z and v(0) is a uniquely defined velocity scale. The
      number kappa is universal, and measurements over several decades have shown that
      it is nearly 0.42. We use a randomly stirred model of turbulence to derive the
      above law and find kappa=sqrt[108/125pi] approximately 0.52.

PMID- 11304353
TI  - Localized perturbations in binary fluid convection with and without throughflow.
AB  - Dynamics and structure of spatially localized convective perturbations in binary
      fluid layers heated from below and the effect of a plane horizontal Poiseuille
      throughflow on them are investigated. Fronts and pulse-like wave packets formed
      out of the three relevant perturbations-two oscillatory ones and a stationary one
      are analyzed after evaluating the appropriate saddle points of the three
      respective dispersion relations of the linear field equations over the complex
      wave number plane. Front and pulse properties are elucidated in quantitative
      detail as a function of small throughflow Reynolds numbers for different Soret
      coupling strengths psi including the pure fluid limit psi=0 in comparison with
      the appropriate Ginzburg-Landau amplitude equation approximations. Furthermore,
      small amplitude pulses and fronts obtained from solving the full nonlinear field
      equations numerically are presented to check and compare with the linear results.

PMID- 11304354
TI  - Anomalous scaling of anisotropy of second-order moments in a model of a randomly
      advected solenoidal vector field.
AB  - A model of randomly advected solenoidal field is presented. The model is formally
      derived by a linearization of the Navier-Stokes equation with respect to the
      perturbation to a basic state and by assuming the characteristic time scale of
      the basic state to be very short. The model includes a nonlocal (in space) effect
      through a pressurelike term that keeps the advected field solenoidal, but still
      yields exact equations for multipoint moments. The advecting field is assumed to
      be statistically homogeneous and isotropic with zero mean and structure function
      with exponent xi. An analysis is made of the scaling of the steady second-order
      moments of the solenoidal field in two dimensions. The scaling exponent zeta(l)
      of the isotropic part (l=0) and the anisotropic part for the angular wave number
      l=2 is obtained analytically or numerically. The scaling of the isotropic part
      does not depend on whether the pressurelike term is present or not while the
      scaling of the anisotropic part is affected by the pressurelike term. There are
      two homogeneous similarity solutions with real positive exponents zeta(2) when
      xi>xi(c)(2) approximately 1.3. The same kind of analysis is also applied to a
      simplified two-point closure equation.

PMID- 11304355
TI  - Anomalous scaling of a passive scalar in the presence of strong anisotropy.
AB  - Field theoretic renormalization group and the operator product expansion are
      applied to a model of a passive scalar quantity straight theta(t,x), advected by
      the Gaussian strongly anisotropic velocity field with the covariance infinity
      delta(t-t('))/x-x(')/(epsilon). Inertial-range anomalous scaling behavior is
      established, and explicit asymptotic expressions for the structure functions
      S(n)(r) identical with<[straight theta(t,x+r)-straight theta(t,x)](n)> are
      obtained. They are represented by superpositions of power laws; the corresponding
      anomalous exponents, which depend explicitly on the anisotropy parameters, are
      calculated to the first order in epsilon in any space dimension d. In the limit
      of vanishing anisotropy, the exponents are associated with tensor composite
      operators built of the scalar gradients, and exhibit a kind of hierarchy related
      to the degree of anisotropy: the less is the rank, the less is the dimension and,
      consequently, the more important is the contribution to the inertial-range
      behavior. The leading terms of the even (odd) structure functions are given by
      the scalar (vector) operators. For the finite anisotropy, the exponents cannot be
      associated with individual operators (which are essentially "mixed" in
      renormalization), but the aforementioned hierarchy survives for all the cases
      studied. The second-order structure function S2 is studied in more detail using
      the renormalization group and zero-mode techniques; the corresponding exponents
      and amplitudes are calculated within the perturbation theories in epsilon, 1/d,
      and in the anisotropy parameters. If the anisotropy of the velocity is strong
      enough, the skewness factor S(3)/S(3/2)(2) increases going down towards the depth
      of the inertial range; the higher-order odd ratios increase even if the
      anisotropy is weak.

PMID- 11304356
TI  - Observation of bubble dynamics within luminescent cavitation clouds:
      Sonoluminescence at the nano-scale.
AB  - Measurements of acoustically driven cavitation luminescence indicate that this
      phenomenon is robust over a huge parameter space ranging from 10 kHz to >10 MHz.
      The minimum bubble radius achieved is an upper bound for the size of the light
      emitting region and ranges from about 1 microm at 15 kHz to tens of nm at 11 MHz.
      Although lines can be discerned in the spectra of some cavitation clouds, they
      sit on top of a broadband continuum which can have greater spectral density in
      the ultraviolet than is observed for resonantly driven sonoluminescence from a
      single bubble.

PMID- 11304357
TI  - Gravity-driven instability in a spherical Hele-Shaw cell.
AB  - A pair of concentric spheres separated by a small gap form a spherical Hele-Shaw
      cell. In this cell an interfacial instability arises when two immiscible fluids
      flow. We derive the equation of motion for the interface perturbation amplitudes,
      including both pressure and gravity drivings, using a mode coupling approach.
      Linear stability analysis shows that mode growth rates depend upon interface
      perimeter and gravitational force. Mode coupling analysis reveals the formation
      of fingering structures presenting a tendency toward finger tip-sharpening.

PMID- 11304358
TI  - Chaotic properties of dilute two- and three-dimensional random Lorentz gases. II.
      Open systems.
AB  - We calculate the spectrum of Lyapunov exponents for a point particle moving in a
      random array of fixed hard disk or hard sphere scatterers, i.e., the disordered
      Lorentz gas, in a generic nonequilibrium situation. In a large system which is
      finite in at least some directions, and with absorbing boundary conditions, the
      moving particle escapes the system with probability one. However, there is a set
      of zero Lebesgue measure of initial phase points for the moving particle, such
      that escape never occurs. Typically, this set of points forms a fractal repeller,
      and the Lyapunov spectrum is calculated here for trajectories on this repeller.
      For this calculation, we need the solution of the recently introduced extended
      Boltzmann equation for the nonequilibrium distribution of the radius of curvature
      matrix and the solution of the standard Boltzmann equation. The escape-rate
      formalism then gives an explicit result for the Kolmogorov Sinai entropy on the
      repeller.

PMID- 11304359
TI  - Nonhydrodynamic aspects of electron transport near a boundary: the Milne problem.
AB  - The nonhydrodynamic behavior of electrons near a boundary is studied with the
      Milne problem of transport theory. A system of electrons dilutely dispersed in a
      heat bath of atomic moderators is considered in the positive one-dimensional
      spatial half-space with an absorbing boundary at the origin which mimics an
      electrode. A flux of electrons is assumed to originate at an infinite distance
      from the boundary. The Fokker-Planck equation for the electron distribution
      function in space and velocity is considered. The density and temperature
      profiles are determined, and the departure from hydrodynamic behavior near the
      boundary is studied. Argon and helium are chosen as the moderators, and results
      with different cross sections are obtained. The Fokker-Planck equation is solved
      with an expansion in Legendre and Speed polynomials, and compared wherever
      possible with results obtained with a Monte Carlo simulation. The behavior near
      the boundary is shown to be strongly influenced by the Ramsauer-Townsend minimum
      in the electron-Ar momentum transfer cross section.

PMID- 11304361
TI  - Statistical theory of dusty plasmas: microscopic equations and Bogolyubov-Born
      Green-Kirkwood-Yvon hierarchy.
AB  - Basic principles of statistical theory of dusty plasmas are formulated with
      regard for electron and ion absorption by dust particles. Rigorous microscopic
      equations are introduced and employed to derive the BBGKY hierarchy and kinetic
      equations. The charging processes are shown to induce a considerable modification
      of both microscopic and kinetic equations for plasma particles and grains. In the
      approximation of dominant influence of charging collisions, explicit kinetic
      equations are derived and applied to calculate stationary distributions of grain
      velocities and charges.

PMID- 11304360
TI  - Metallization of hydrogen using heavy-ion-beam implosion of multilayered
      cylindrical targets.
AB  - Employing a two-dimensional simulation model, this paper presents a suitable
      design for an experiment to study metallization of hydrogen in a heavy-ion beam
      imploded multilayered cylindrical target that contains a layer of frozen
      hydrogen. Such an experiment will be carried out at the upgraded heavy-ion
      synchrotron facility (SIS-18) at the Gesellschaft fur Schwerionenforschung,
      Darmstadt by the end of the year 2001. In these calculations we consider a
      uranium beam that will be available at the upgraded SIS-18. Our calculations show
      that it may be possible to achieve theoretically predicted physical conditions
      necessary to create metallic hydrogen in such experiments. These include a
      density of about 1 g/cm(3), a pressure of 3-5 Mbar, and a temperature of a few
      0.1 eV.

PMID- 11304362
TI  - Model for the generation of toroidal and poloidal magnetic fields in a laser
      produced plasma.
AB  - A mechanism of simultaneous generation of toroidal and poloidal magnetic fields
      in an underdense region of a laser-produced plasma is discussed. The mechanism
      relies on the fact that at least a part of the incident transverse mode of the
      laser field undergoes a linear conversion into a longitudinal mode in the thermal
      plasma. It involves the conversion of ordered kinetic motion of the charged
      particles in the presence of the field into the energy of the induced magnetic
      fields both in poloidal and toroidal directions. The analysis is based on
      obtaining perturbative solutions of the two-fluid model of a hot nondissipative
      plasma. Our numerical results show that both the toroidal and poloidal fields
      increase with the laser intensity, and that the former dominates over the latter.
      Further, the toroidal fields decrease with increasing pulse lengths and increase
      rather slowly with an increase in laser wavelengths. However, the poloidal fields
      seem to be insensitive to the laser pulse lengths but they increase exponentially
      with the laser wavelengths. Finally, toroidal fields have a tendency to decrease
      as the critical surface is approached. The poloidal fields show a contrary
      behavior.

PMID- 11304363
TI  - Time of flight measurements on ion-velocity distribution and anisotropy of ion
      temperatures in laser plasmas.
AB  - Using a 200-mJ, 5-ns, Nd:YAG laser (where YAG denotes yttrium aluminum garnet),
      time of flight spectra for ions produced from slab targets of carbon, aluminum,
      nickel, and tantalum were obtained at a laser intensity of approximately 5x10(10)
      W/cm(2). The velocity distribution function of ions of each ionization state, at
      several angles, in the plane of incidence, was investigated and was observed to
      depart significantly from the Maxwell-Boltzmann distribution function. Kinetic
      temperatures of ions of each ionization state were estimated separately at
      various angles in the plane of incidence and were observed to show a highly
      anisotropic property leading one to conclude that the equipartition of energy
      between the plasma electrons and ions has not taken place. The results are
      discussed and the relevant conclusions are presented.

PMID- 11304364
TI  - Time-dependent electron-ion collision frequency at arbitrary laser intensity
      temperature ratio.
AB  - In superintense laser beams collisional absorption exhibits a large amplitude
      modulation over a laser cycle. In this paper formulas for the time-dependent
      electron-ion collision frequency nu(ei)(t) are presented. On the basis of a
      ballistic interaction model we deduce an expression for nu(ei)(t) which holds for
      an arbitrary isotropic distribution function and arbitrary anharmonic oscillatory
      electron motion [Eq. (4)]. For a Maxwellian we present compact formulas for the
      various ratios v(os)(t)/v(th). It is shown that the strong time dependence over
      one laser cycle leads to the generation of intense odd harmonics. The cycle
      averaged collision frequency nu(ei);(t) is compared with expressions derived from
      the more complex dielectric model. It is shown that the correct choice of cutoffs
      as a consequence of dynamical screening is essential.

PMID- 11304365
TI  - N+ charge transfer and N+2 dissociation in N2 at swarm energies.
AB  - This paper reports a drift-tube-mass-spectrometer measurement of the relative
      abundances of N+ and N+2 in pure nitrogen, over a ratio of electric field to gas
      density, E/N, from 800 to 7200 Td [1 townsend (Td)=10(-17) V cm(2)]. A proposed
      charge transfer dissociation scheme between the above two ions and N2 allowed us
      to obtain spatial rate coefficients for charge transfer and dissociation over the
      E/N range 800-2800 Td. Using previously measured cross sections for the above
      processes, and assuming a Maxwellian distribution of ion velocities, we
      calculated the reaction coefficients, which were found to be in good agreement
      with our measured values. In particular, the present results support the trend
      toward fairly high charge transfer cross section values for N+ energies above 10
      eV. In the overlap range between 2.4 and 7.2 kTd, our concentration ratio
      [N(+)/N(+)(2)] is about five times smaller than that measured previously from a
      diffuse Townsend discharge in which electron impact is involved in addition to
      N+2 collisional dissociation with N2, but has the same trend. Thus it seems that,
      besides N+2 dissociation by electron impact, collisional dissociation becomes
      important at elevated values of E/N. In connection with previous discharge work
      in nitrogen, the present study may help explain the enhanced cathode yields
      observed.

PMID- 11304366
TI  - Feedback of a small-scale magnetic dynamo.
AB  - We develop a WKB approach to the rapid distortion theory for magnetohydrodynamic
      turbulence with large magnetic Prandtl number. Within this theory, we study the
      growth of small-scale magnetic fluctuations in a large-scale velocity field being
      initially a pure strain. We show that the magnetic Lorentz force excites a
      secondary flow in the form of counterrotating vortices on the periphery of the
      magnetic spot. Those vortices slow down stretching of the magnetic spot and thus
      provide a negative feedback for a small-scale magnetic dynamo.

PMID- 11304367
TI  - Anisotropic dust lattice modes.
AB  - Dust lattice (DL) wave modes in a one-dimensional plasma crystal suspended in the
      plasma sheath are studied. The ion flow in the sheath introduces an anisotropy,
      in particular "ion wakes" below the crystal particles. This leads to two types of
      transverse wave mode. It is shown that the "horizontal transverse mode" remains
      independent, but the "vertical transverse mode" and the longitudinal mode are
      coupled due to the particle-wake interaction. The coupling can drive an
      instability of the modes close to the point where their branches intersect. In
      addition, the particle-wake interaction might decrease the frequencies of the DL
      modes considerably.

PMID- 11304368
TI  - Bohm criterion for a plasma composed of electrons and positive dust grains.
AB  - An investigation is presented of a collisionless sheath of a dusty plasma whose
      constituents are positively charged dust grains and electrons. Accounting for the
      Boltzmann electron density distribution and the hydrodynamic dust fluid model,
      supplemented by Poisson and dust charging equations, a space-charge sheath model
      is developed. The Bohm criterion for a dusty plasma system with electrons and
      positive dust grains is deduced. The results can have relevance to space and
      laboratory plasmas.

PMID- 11304369
TI  - Laser-produced plasma bubble.
AB  - In the aftermath of a plasma in atmospheric density H2 produced by a 6 ns, 600
      mJ, 1064 nm, Nd:YAG laser pulse, a bubble develops behind the shock front. Within
      2 micros the shock detaches from it, but the bubble persists for 100 micros
      before it is clearly turbulent. While initially spheroidal in appearance with a
      diameter of about 0.6 cm, after 16 micros the enveloping cold gas penetrates the
      bubble along the axial channel left by the laser. This results in a distorted
      torus with a protrusion that moves slowly toward the laser. The images show that
      the gas processed by the laser-plasma shock front is isolated from the
      surrounding unprocessed gas until mixed by this flow.

PMID- 11304370
TI  - Stochastic collective dynamics of charged-particle beams in the stability regime.
AB  - We introduce a description of the collective transverse dynamics of charged
      (proton) beams in the stability regime by suitable classical stochastic
      fluctuations. In this scheme, the collective beam dynamics is described by time
      reversal invariant diffusion processes deduced by stochastic variational
      principles (Nelson processes). By general arguments, we show that the diffusion
      coefficient, expressed in units of length, is given by lambda(c)sqrt[N], where N
      is the number of particles in the beam and lambda(c) the Compton wavelength of a
      single constituent. This diffusion coefficient represents an effective unit of
      beam emittance. The hydrodynamic equations of the stochastic dynamics can be
      easily recast in the form of a Schrodinger equation, with the unit of emittance
      replacing the Planck action constant. This fact provides a natural connection to
      the so-called "quantum-like approaches" to beam dynamics. The transition
      probabilities associated to Nelson processes can be exploited to model evolutions
      suitable to control the transverse beam dynamics. In particular we show how to
      control, in the quadrupole approximation to the beam-field interaction, both the
      focusing and the transverse oscillations of the beam, either together or
      independently.

PMID- 11304371
TI  - Stochastic resonance in free-electron lasers.
AB  - We present evidence of stochastic resonance in free-electron lasers. In order to
      do that, we have analyzed theoretically the dynamics of a free-electron laser
      oscillator. A weak modulation and a noise source have been applied to the initial
      energy of the electron beam. We have found stochastic resonance for different
      frequencies and amplitudes of the modulation. A threshold crossing mechanism
      leads to the stochastic resonance in this system.

PMID- 11304372
TI  - Nontopological solitary waves in continuous and discrete one-component molecular
      chains.
AB  - It is shown that the nontopological (bell-shaped) solitary waves in the
      asymmetric straight phi(4) model are unstable and correspond to saddle points of
      the potential energy of the continuous system. Their lifetime is estimated. In
      the discrete model, the potential energy landscape becomes rough: bell-shaped
      configurations may become stable. The potential energy function is analyzed
      around the bell-shaped configurations. A dynamical scenario for the decay of the
      metastable state in a discrete system, related to spontaneous energy
      localization, is shown.

PMID- 11304373
TI  - Compression of femtosecond laser pulses in thin one-dimensional photonic
      crystals.
AB  - We demonstrate experimentally the effect of compression of femtosecond laser
      pulses in thin (a few micrometers) one-dimensional photonic crystal. We show that
      the compression effect is reasonably described by the linear dispersion
      properties of the photonic crystal itself and the quadratic dispersion
      approximation cannot be efficiently used for the description of interaction of
      the femtosecond laser pulses with the thin photonic crystal. For given parameters
      of the femtosecond pulse it leads to the existence of the optimal dimension of
      the photonic crystal from the point of view of the compression efficiency. Due to
      the wide spectral width of the femtosecond laser pulses the high-order dispersion
      effects play an important role in pulse propagation in photonic crystals and as a
      result the pulse compression occurs for both positive and negative signs of chirp
      of the incoming femtosecond pulses.

PMID- 11304374
TI  - Self-bending of the coupled spatial soliton pairs in a photorefractive medium
      with drift and diffusion nonlinearity.
AB  - The propagation of two incoherently coupled laser beams (coupled soliton pairs)
      in the photorefractive crystal with drift and diffusion components of nonlinear
      response is investigated. By the effective particles method we have shown that
      not only the well-known Manakov's soliton pairs but also asymmetric pairs can
      propagate undistorted in photorefractive crystal with diffusion nonlinearity
      along the parabolic trajectory for the definite relations of propagation
      constants. We numerically found the exact profiles of the specific multihump
      soliton solutions that are possible only in the photorefractive medium with
      nonlocal diffusion response. The stability properties and specific features of
      pair collisions are analyzed.

PMID- 11304375
TI  - Influence of walkoff on pattern formation in nondegenerate optical parametric
      oscillators.
AB  - Convective and absolute nature of instabilities in nondegenerate optical
      parametric oscillators with large transverse section, for negative detunings and
      in the presence of walkoff, is examined. The asymptotic response of the signal
      and idler fields to a transverse localized two-dimensional perturbation is
      evaluated. The presence of walkoff breaks the rotational symmetry in the
      transverse plane, and the system, at the absolute instability threshold, selects
      traveling waves propagating in the walkoff direction among an infinity of
      unstable spatiotemporal modes. We show that in optical parametric oscillators
      (OPO's) with negative detunings, contrary to the case of positive detunings, the
      walkoff shrinks the region of convective instabilities, and even may suppress the
      convective/absolute transition. Hence, in a certain range of parameters, signal
      field envelopes in the form of wave packets of zero group velocity are found
      where the instability is absolute at the onset, although the walkoff is present.
      We also show that nonlinear pattern selection is ruled by the cross-coupling
      terms appearing in the asymmetric coupled Ginzburg-Landau equations derived near
      threshold of the signal and idler generation. The numerical solutions of the
      original OPO equations confirm the analytical predictions for the values of the
      instability thresholds and the corresponding selected patterns.

PMID- 11304376
TI  - Stable vortex solitons in the two-dimensional Ginzburg-Landau equation.
AB  - In the framework of the complex cubic-quintic Ginzburg-Landau equation, we
      perform a systematic analysis of two-dimensional axisymmetric doughnut-shaped
      localized pulses with the inner phase field in the form of a rotating spiral. We
      put forward a qualitative argument which suggests that, on the contrary to the
      known fundamental azimuthal instability of spinning doughnut-shaped solitons in
      the cubic-quintic NLS equation, their GL counterparts may be stable. This is
      confirmed by massive direct simulations, and, in a more rigorous way, by
      calculating the growth rate of the dominant perturbation eigenmode. It is shown
      that very robust spiral solitons with (at least) the values of the vorticity S=0,
      1, and 2 can be easily generated from a large variety of initial pulses having
      the same values of intrinsic vorticity S. In a large domain of the parameter
      space, it is found that all the stable solitons coexist, each one being a strong
      attractor inside its own class of localized two-dimensional pulses distinguished
      by their vorticity. In a smaller region of the parameter space, stable solitons
      with S=1 and 2 coexist, while the one with S=0 is absent. Stable breathers, i.e.,
      both nonspiraling and spiraling solitons demonstrating persistent quasiperiodic
      internal vibrations, are found too.

PMID- 11304377
TI  - Analytical solution of the polarized photon transport equation in an infinite
      uniform medium using cumulant expansion.
AB  - An analytical solution for time-dependent polarized photon transport equation in
      an infinite uniform isotropic medium is studied using a circular representation
      of the polarized light and expansion in the generalized spherical functions. We
      extend our cumulant approach for solving the scalar (unpolarized) photon
      transport equation to the vector (polarized) case. As before, an exact angular
      distribution is obtained and a cumulant expansion is derived for the polarized
      photon distribution function. By a cutoff at the second cumulant order, a
      Gaussian analytical approximate expression of the polarized photon spatial
      distribution is obtained as a function of the direction of light and time, whose
      average center position and half-width are always exact. The central limit
      theorem claims that this spatial distribution approaches accuracy in detail when
      the number of collisions or time becomes large. The analytical expression of
      cumulants up to an arbitrary high order is also derived, which can be used for
      calculating a more accurate polarized photon distribution through a numerical
      Fourier transform. Contrary to what occurs in other approximation techniques,
      truncation of the cumulant expansion at order n is exact at that order and
      cumulants up to and including order n remain unchanged when higher orders are
      added, at least as applied in our photon transport equation.

PMID- 11304378
TI  - Photorefractive light scattering families in (111)-cut Bi12TiO20 crystals with an
      external electric ac field.
AB  - We investigate here both theoretically and experimentally light-induced
      scattering in (111)-cut Bi12TiO20 crystals with an external ac field. Our simple
      analytic solution, which is nearly as precise as the numeric one, allows us to
      recognize the following otherwise hidden general features. Without the elasto
      optic contribution, the scattering patterns are identical for the same value of
      xi=zeta(0)+(2/3)straight phi(p), where straight phi(p) is the initial
      polarization angle and zeta(0) is the angle of the external field. With the
      elasto-optic contribution, the scattering patterns for the same xi are still very
      similar. For xi not equal0, the scattering patterns depend differently on the
      elasto-optic coefficients p(12) and p(13) so that in principle p(12) and p(13)
      can be measured by purely holographic experiments. On the experimental side, we
      present scattering patterns for xi=0 and +/-30 degrees, showing thereby the
      similarity of the scattering patterns for equal values of xi. In all cases, we
      obtain good qualitative agreement of our analytic and numeric calculations with
      the experimental findings.

PMID- 11304379
TI  - Time-gated Manakov spatial solitons are computationally universal.
AB  - We prove that time-gated Manakov (1+1)-dimensional spatial solitons can perform
      arbitrary computation in a homogeneous medium with beams entering only at one
      boundary.

PMID- 11304380
TI  - Limits for interchannel frequency separation in a soliton wavelength-division
      multiplexing system.
AB  - We identify the required interchannel frequency separation of the input field for
      a soliton wavelength-division multiplexing (WDM) system. It is found that the
      critical frequency separation above which WDM with solitons is feasible increases
      with the number of transmission channels. Moreover, it is shown that a
      combination of time- and wavelength-division multiplexing yields the largest
      transmission capacity. Finally, the structure of the soliton spectra which
      correspond to the frequency separation smaller than the critical frequency is
      discussed.

PMID- 11304381
TI  - Solitons in nonlocal nonlinear media: exact solutions.
AB  - We investigate the propagation of one-dimensional bright and dark spatial
      solitons in a nonlocal Kerr-like media, in which the nonlocality is of general
      form. We find an exact analytical solution to the nonlinear propagation equation
      in the case of weak nonlocality. We study the properties of these solitons and
      show their stability.

PMID- 11304382
TI  - Near equilibrium dynamics of nonhomogeneous Kirchhoff filaments in viscous media.
AB  - We study the near equilibrium dynamics of nonhomogeneous elastic filaments in
      viscous media using the Kirchhoff model of rods. Viscosity is incorporated in the
      model as an external force, which we approximate by the resistance felt by an
      infinite cylinder immersed in a slowly moving fluid. We use the recently
      developed method of Goriely and Tabor [Phys. Rev. Lett. 77, 3537 (1996); Physica
      D 105, 20 (1997); 105, 45 (1997)] to study the dynamics in the vicinity of the
      simplest equilibrium solution for a closed rod with nonhomogeneous distribution
      of mass, namely, the planar ring configuration. We show that small variations of
      the mass density along the rod are sufficient to couple the symmetric modes of
      the homogeneous rod problem, producing asymmetric deformations that modify
      substantially the dynamical coiling, even at quite low Reynolds number. The
      higher-density segments of the rod tend to become more rigid and less coiled. We
      comment on possible applications to DNA.

PMID- 11304383
TI  - Multimode soliton dynamics in perturbed ladder lattices.
AB  - We investigate the interplay between the longitudinal and lateral solitonic modes
      in perturbed ladder lattices in regard to the transmission of soliton wave
      packet. (1) In a longitudinal uniform field the lateral and longitudinal
      solitonic modes are shown to be independent. However, unlike in the unperturbed
      case the dynamics of the soliton center of mass becomes confined within a finite
      spatial domain via the Bloch-Zener mechanism in the longitudinal direction and
      due to the transverse finiteness of the ladder in the lateral one. (2) The
      segment of on-site impurities causes the soliton mode-mode mixing. As a result
      the soliton exhibits rather complex two- or three-dimensional dynamics
      accompanied by wave radiation which may give rise to soliton trapping.
      Nevertheless, under some specific conditions the soliton is able to bypass even
      the strong impurities slaloming between them. In particular, the slalom soliton
      dynamics is possible on a ladder lattice with a segment of zigzig-distributed on
      site impurities. We formulate the conditions favorable to the case and show that
      their violation gives rise to either soliton trapping on or soliton reflection
      from the impure segment. (3) Finally, we study the effect of the modified
      transverse bond on the longitudinal soliton dynamics and reveal that it might act
      on the soliton as either an attractive or a repulsive potential, depending on the
      sign of the transverse energy of the ingoing soliton. The effect is essentially a
      solitonic one and becomes strictly pronounced for heavy solitons, when
      imperfection-induced radiation effects are exponentially suppressed. We expect
      that transverse-bond imperfection could serve as a filter selecting the solitons
      with prescribed properties. A similar function is feasible for zigzag-distributed
      on-site impurities too.

PMID- 11304384
TI  - Classical theory of resonant transition radiation in multilayer structures.
AB  - A rigorous classical electromagnetic theory of the transition radiation in finite
      and infinite multilayer structures is presented. It makes the standard results of
      thin-film optics, such as the matrix formalism, accountable; it allows thus an
      exact treatment of the propagation of the waves induced by the electron. This
      method is applied to the particular case of the periodic structures to treat the
      resonant transition radiation (RTR). It is noted that the present theory gives,
      in the hard x-ray domain, results previously published. The reason for this
      approach is to make the numerical calculations rigorous and easy. The numerical
      results of our theory are compared to experimental RTR data obtained recently by
      Yamada et al. [Phys. Rev. A 59, 3673 (1999)] with a nickel-carbon multilayer
      structure.

PMID- 11304385
TI  - Crossing of identical solitary waves in a chain of elastic beads.
AB  - We consider a chain of elastic beads subjected to vanishingly weak loading
      conditions, i.e., the beads are barely in contact. The grains repel upon contact
      via the Hertz-type potential, Vinfinitydelta(n), n>2, where delta> or =0, delta
      being the grain-grain overlap. Our dynamical simulations build on several earlier
      studies by Nesterenko, Coste, and Sen and co-workers that have shown that an
      impulse propagates as a solitary wave of fixed spatial extent (dependent only
      upon n) through a chain of Hertzian beads and demonstrate, to our knowledge for
      the first time, that colliding solitary waves in the chain spawn a well-defined
      hierarchy of multiple secondary solitary waves, which is approximately 0.5% of
      the energy of the original solitary waves. Our findings have interesting
      parallels with earlier observations by Rosenau and colleagues [P. Rosenau and J.
      M. Hyman, Phys. Rev. Lett. 70, 564 (1993); P. Rosenau, ibid. 73, 1737 (1994);
      Phys. Lett. A 211, 265 (1996)] regarding colliding compactons. To the best of our
      knowledge, there is no formal theory that describes the dynamics associated with
      the formation of secondary solitary waves. Calculations suggest that the
      formation of secondary solitary waves may be a fundamental property of certain
      discrete systems.

PMID- 11304386
TI  - Parametric localized modes in quadratic nonlinear photonic structures.
AB  - We analyze two-color spatially localized nonlinear modes formed by parametrically
      coupled fundamental and second-harmonic fields excited at quadratic (or chi(2))
      nonlinear interfaces embedded in a linear layered structure--a quadratic
      nonlinear photonic crystal. For a periodic lattice of nonlinear interfaces, we
      derive an effective discrete model for the amplitudes of the fundamental and
      second-harmonic waves at the interfaces (the so-called discrete chi(2) equations)
      and find, numerically and analytically, the spatially localized solutions-
      discrete gap solitons. For a single nonlinear interface in a linear superlattice,
      we study the properties of two-color localized modes, and describe both
      similarities to and differences from quadratic solitons in homogeneous media.

PMID- 11304387
TI  - Parallel excluded volume tempering for polymer melts.
AB  - We have developed a technique to accelerate the acquisition of effectively
      uncorrelated configurations for off-lattice models of dense polymer melts that
      makes use of both parallel tempering and large-scale Monte Carlo moves. The
      method is based upon simulating a set of systems in parallel, each of which has a
      slightly different repulsive core potential, such that a thermodynamic path from
      full excluded volume to an ideal gas of random walks is generated. While each
      system is run with standard stochastic dynamics, resulting in an NVT ensemble, we
      implement the parallel tempering through stochastic swaps between the
      configurations of adjacent potentials, and the large-scale Monte Carlo moves
      through attempted pivot and translation moves that reach a realistic acceptance
      probability as the limit of the ideal gas of random walks is approached. Compared
      to pure stochastic dynamics, this results in an increased efficiency even for a
      system of chains as short as N=60 monomers, however at this chain length the
      large-scale Monte Carlo moves were ineffective. For even longer chains, the
      speedup becomes substantial, as observed from preliminary data for N=200. We also
      compare our scheme to the end bridging algorithm of Theodorou et al. For N=60,
      end bridging must allow a polydispersity of more than 10% in order to relax the
      end-to-end vector more quickly than our method. The comparison is, however,
      hampered by the fact that the end-to-end vector becomes a somewhat artificial
      quantity when one implements end bridging, and is perhaps no longer the slowest
      dynamic variable.

PMID- 11304388
TI  - Efficient dynamic importance sampling of rare events in one dimension.
AB  - Exploiting stochastic path-integral theory, we obtain by simulation substantial
      gains in efficiency for the computation of reaction rates in one-dimensional,
      bistable, overdamped stochastic systems. Using a well-defined measure of
      efficiency, we compare implementations of "dynamic importance sampling" (DIMS)
      methods to unbiased simulation. The best DIMS algorithms are shown to increase
      efficiency by factors of approximately 20 for a 5k(B)T barrier height and 300 for
      9k(B)T, compared to unbiased simulation. The gains result from close emulation of
      natural (unbiased), instantonlike crossing events with artificially decreased
      waiting times between events that are corrected for in rate calculations. The
      artificial crossing events are generated using the closed-form solution to the
      most probable crossing event described by the Onsager-Machlup action. While the
      best biasing methods require the second derivative of the potential (resulting
      from the "Jacobian" term in the action, which is discussed at length), algorithms
      employing solely the first derivative do nearly as well. We discuss the
      importance of one-dimensional models to larger systems, and suggest extensions to
      higher-dimensional systems.

PMID- 11304389
TI  - Fourth-order algorithms for solving the multivariable Langevin equation and the
      Kramers equation.
AB  - We develop a fourth-order simulation algorithm for solving the stochastic
      Langevin equation. The method consists of identifying solvable operators in the
      Fokker-Planck equation, factorizing the evolution operator for small time steps
      to fourth order, and implementing the factorization process numerically. A key
      contribution of this paper is to show how certain double commutators in the
      factorization process can be simulated in practice. The method is general,
      applicable to the multivariable case, and systematic, with known procedures for
      doing fourth-order factorizations. The fourth-order convergence of the resulting
      algorithm allowed very large time steps to be used. In simulating the Brownian
      dynamics of 121 Yukawa particles in two dimensions, the converged result of a
      first-order algorithm can be obtained by using time steps 50 times as large. To
      further demonstrate the versatility of our method, we derive two new classes of
      fourth-order algorithms for solving the simpler Kramers equation without
      requiring the derivative of the force. The convergence of many fourth-order
      algorithms for solving this equation are compared.

PMID- 11304390
TI  - Self-organization in systems of self-propelled particles.
AB  - We investigate a discrete model consisting of self-propelled particles that obey
      simple interaction rules. We show that this model can self-organize and exhibit
      coherent localized solutions in one- and in two-dimensions. In one-dimension, the
      self-organized solution is a localized flock of finite extent in which the
      density abruptly drops to zero at the edges. In two-dimensions, we focus on the
      vortex solution in which the particles rotate around a common center and show
      that this solution can be obtained from random initial conditions, even in the
      absence of a confining boundary. Furthermore, we develop a continuum version of
      our discrete model and demonstrate that the agreement between the discrete and
      the continuum model is excellent.

PMID- 11304391
TI  - Generalized strategies in the minority game.
AB  - We show analytically how the fluctuations (i.e., standard deviation sigma) in the
      minority game can decrease below the random coin-toss limit if the agents use
      more general, stochastic strategies. This suppression of sigma results from a
      cancellation between the actions of a crowd, in which agents act collectively and
      make the same decision, and those of an anticrowd, in which agents act
      collectively by making the opposite decision to the crowd.

PMID- 11304392
TI  - Optimized chaos control with simple limiters.
AB  - We present an elementary derivation of chaos control with simple limiters using
      the logistic map and the Henon map as examples. This derivation provides
      conditions for optimal stabilization of unstable periodic orbits of a chaotic
      attractor.

PMID- 11304393
TI  - Analysis of spatiotemporally periodic behavior in lattices of coupled piecewise
      monotonic maps.
AB  - We study the stability of spatiotemporally periodic orbits in 1-d lattices of
      piecewise monotonic maps coupled via translationally invariant coupling and
      periodic boundary conditions. States of such systems have independent spatial and
      temporal periodicities and their stability can be studied through the analysis of
      a single, uniquely identified reduced matrix of size kxk when the system size is
      MxM, for M=kN, a multiple of k. This result applies for arbitrary temporal
      periods and is valid for all coupled map lattice systems coupled in a
      translationally invariant manner with stability matrices which are irreducible
      and non-negative, as in the present case. Our analysis could be useful in the
      analysis of stability regions and bifurcation behavior in a variety of spatially
      extended systems.

PMID- 11304394
TI  - Driven, underdamped Frenkel-Kontorova model on a quasiperiodic substrate.
AB  - We consider the underdamped dynamics of a chain of atoms subject to a dc driving
      force and a quasiperiodic substrate potential. The system has three inherent
      length scales which we take to be mutually incommensurate. We find that when the
      length scales are related by the spiral mean (a cubic irrational) there exists a
      value of the interparticle interaction strength above which the static friction
      is zero. When the length scales are related by the golden mean (a quadratic
      irrational) the static friction is always nonzero. From considerations based on
      the connection of this problem to standard map theory, we postulate that zero
      static friction is generally possible for incommensurate ratios of the length
      scales involved. However, when the length scales are quadratic irrationals, or
      have some commensurability with each other, the static friction will be nonzero
      for all choices of interaction parameters. We also comment on the nature of the
      depinning mechanisms and the steady states achieved by the moving chain.

PMID- 11304395
TI  - Plasma kinetics around a dust grain in an ion flow.
AB  - The kinetics of plasma particles around a stationary dust grain in the presence
      of an ion flow is studied using a three-dimensional molecular dynamics simulation
      method. The model is self-consistent, involving the dynamics of plasma electrons
      and ions as well as charging of the dust grain. The effect of ion focusing is
      investigated as a function of the ion flow velocity. Distributions of electron
      and ion number densities, and electrostatic plasma potential are obtained.

PMID- 11304396
TI  - Radiometric force in dusty plasmas.
AB  - It is shown that inhomogeneous heating of the dust grain by ion flow in a glow
      discharge results in a photophoresislike force. According to our estimations,
      this radiometric force can be comparably-valued with the ion-drag force under the
      conditions of microgravity dusty plasma experiments.

PMID- 11304397
TI  - Complications associated with radiofrequency catheter ablation of cardiac
      arrhythmias.
AB  - Catheter ablation using radiofrequency energy has evolved as a safe and effective
      means for the treatment of various supraventricular and ventricular arrhythmias.
      Despite the overall efficacy of radiofrequency catheter ablation, cardiovascular
      complications can occur in a small number of patients. The purpose of this
      article is to review the current understanding of the risks and complications
      that can occur during catheter ablation procedures.

PMID- 11304398
TI  - Techniques in orthotopic cardiac transplantation: a review.
AB  - Cardiac transplantation currently is the most effective therapy for end-stage
      heart failure. Since the origination of the standard biatrial technique,
      alternative methods such as the bicaval and "total" techniques have been devised
      with the hope of improving postoperative physiologic and clinical parameters. In
      general, the newer techniques are at least as effective as the original technique
      with respect to arrhythmia, valvular function, hemodynamics, exercise capacity,
      and survival, but whether any one technique offers clear benefits over another
      has been controversial. The bicaval technique is most commonly used today, and
      the general consensus is that this technique ultimately will demonstrate clinical
      superiority.

PMID- 11304399
TI  - Timing of surgery in patients with chronic, severe mitral regurgitation.
AB  - Patients with severe mitral regurgitation (MR) who are managed conservatively
      sustain excess mortality and morbidity. With improved mortality and morbidity
      rates being achieved with surgical management, cardiologists and cardiac surgeons
      are becoming more aggressive in treating patients with severe MR with surgery.
      Recent data indicate that even in the absence of symptoms or left ventricular
      dysfunction, surgery should be offered as a treatment for MR, provided that the
      regurgitation is severe, the valve seems to be repairable, and the surgeon is
      experienced in valve repair and is aided by intraoperative transesophageal
      echocardiography.

PMID- 11304400
TI  - Recent advances in echocardiographic evaluation of left ventricular anatomy,
      perfusion, and function.
AB  - This article provides a brief overview of several recently developed, emerging
      technologies and discusses their potential uses on clinical grounds. These new
      technologies include three-dimensional imaging, objective automated evaluation of
      ventricular function with acoustic quantification, assessment of regional
      ventricular performance using color kinesis and tissue Doppler imaging, harmonic
      imaging, and power Doppler imaging. Our hope is that readers will gain a better
      understanding of the principles underlying these technological advances, which
      will help them to integrate these new techniques efficiently into their clinical
      practices.

PMID- 11304401
TI  - Technetium-99m-labeled myocardial perfusion agents: Are they better than thallium
      201?
AB  - Currently, thallium-201 (201Tl)- and technetium-99m (99mTc)-labeled tracers are
      used interchangeably for the detection of coronary artery disease, the assessment
      of myocardial viability, and risk stratification. This article reviews some of
      the potential advantages and disadvantages of the 99mTc-labeled tracers relative
      to 201Tl. The basic myocardial kinetic properties and biodistribution of the
      commonly used 99mTc-labeled perfusion tracers are compared with those of 201Tl.
      The clinical value of the 99mTc-labeled perfusion tracers is then compared with
      that of 201Tl imaging. With regard to imaging physics and radiation safety, the
      99mTc-labeled tracers are superior to 201Tl. Cost and tracer availability also
      may favor 99mTc-labeled perfusion tracers rather than 201Tl imaging. However, the
      most widely used 99mTc-labeled perfusion tracers currently approved for clinical
      use-99mTc-sestamibi and 99mTc-tetrofosmin-do not track myocardial flow as well as
      201Tl does. This shortcoming of 99mTc-labeled perfusion tracers may reduce the
      sensitivity of these agents in detecting subcritical coronary artery disease. The
      most notable new perfusion agent is 99mTc-labeled bis(N-ethoxy, N-ethyl
      dithiocarbamato) nitrido technetium(v), which is considered to be the 99mTc
      labeled equivalent of 201Tl. However, 99mTc-labeled bis(N-ethoxy, N-ethyl
      dithiocarbamato) nitrido technetium(v) is a neutral compound with kinetic
      properties that are very different from those of 201Tl. Myocardial perfusion
      imaging is often conducted in conjunction with exercise or with different
      pharmacologic stressors, both of which augment regional flow heterogeneity. Each
      of these stressors has unique effects on the coronary vasculature and influences
      the behavior of the radiolabeled perfusion agents. The substantial differences in
      myocardial uptake, clearance kinetics, and biodistribution between each of the
      99mTc-labeled perfusion tracers and 201Tl should be considered in the clinical
      application of perfusion imaging. The myocardial retention of all of the agents
      is affected by myocardial viability. However, 201Tl demonstrates greater
      differential clearance from normal and ischemic regions (redistribution), making
      201Tl a better agent for assessment of viability, particularly in patients with
      extremely low flow. In contrast, agents that do not redistribute, such as 99mTc
      tetrofosmin, might be better for acute assessment of "risk areas" or of chest
      pain. Each of the available perfusion tracers has unique advantages and
      disadvantages that must be considered to ensure its optimal application.

PMID- 11304402
TI  - Thrombosis in the intensive care unit: etiology, diagnosis, management, and
      prevention in adults and children.
AB  - Venous thromboembolism, a well-recognized complication in postoperative patients,
      is emerging as a frequent complication in critically ill patients in intensive
      care units. Diagnosis can be particularly difficult in such patients because
      underlying systemic illnesses may mask common presenting signs and symptoms.
      Although numerous independent risk factors have been identified, the critical
      role of both central venous catheters and prothrombotic disorders as significant
      risk factors is a common theme in the pediatric and adult literature. Various
      diagnostic tests exist, with venography remaining the gold standard and newer,
      less invasive methods such as ultrasonography and impedance plethysmography
      becoming increasingly popular. Standard unfractionated heparin remains the
      mainstay of therapy and prophylaxis, although the use of low molecular weight
      heparins is becoming more commonplace. Thrombolytic therapy continues to be
      reserved for severe, life-threatening, acute thrombosis. In this article, we
      review the common risk factors, diagnostic modalities, and treatment options for
      venous thromboembolism in critically ill adult and pediatric patients.

PMID- 11304403
TI  - (a)20 Anti-human Apolipoprotein(a) Protease Domain.

PMID- 11304404
TI  - (a)23 Anti-human Apolipoprotein(a) Kringle V Domain.

PMID- 11304405
TI  - 1E6H5, 2C8H3, Anti-Recombinant Soybean Calmodulin-1 (rSCaM-1).

PMID- 11304406
TI  - FMU1, FMU2, FMU3, FMU4, FMU5, FMU6, and FMU7 Anti-CD226 (PTA1).

PMID- 11304407
TI  - 4B6 Anti-Dengue-4 Virus, E Recombinant Protein (TERP).

PMID- 11304408
TI  - NM-01 Anti-HIV.

PMID- 11304409
TI  - MAbs Against Progesterone Hormone.

PMID- 11304410
TI  - 1A6, 1F10, 2H4, 4C2, 4G5, 7C4, 8F2, 1F2, 4F4, 16D7 Anti-17 beta-estradiol.

PMID- 11304412
TI  - Anti-Ferritin.

PMID- 11304411
TI  - 1C2 Anti-Platelet Glycoprotein V.

PMID- 11304413
TI  - Optical aggregometry versus the PFA-100: experimental studies in pigs treated
      with propofol.
AB  - An experimental study of platelet aggregation was performed in 22 male Landrace x
      Large-White crossbred pigs treated with propofol at different doses, to compare
      the results of optical aggregometry with those of the PFA-100 (Dade Int., Miami,
      FL, USA), a new platelet function analyzer. Platelet aggregation was analyzed in
      basal blood samples by both methods, after which the pigs were divided into three
      groups: G1, anaesthetic induction with propofol (2 mg/kg intravenously (i.v.));
      G2, anaesthetic induction with propofol (2 mg/kg i.v.), followed by a second dose
      of 1.5 mg/kg; and G3, anaesthetic induction with propofol (2 mg/kg i.v.),
      followed by 1 h of continuous i.v. infusion at 13 mg/kg/h. Four minutes after
      propofol injection, blood samples were again taken from each group and studied by
      both methods. In groups G2 and G3, both methods showed reduced platelet
      aggregation, while in group G1 neither evidenced an anti-aggregating effect of
      propofol. Under our experimental conditions: (1) the propofol effect on platelet
      aggregation depends on the plasma concentration; (2) the results obtained with
      the two methods are comparable; (3) PFA-100 may provide an alternative to optical
      aggregometry for detecting the effects of anaesthetic agents ex vivo.

PMID- 11304414
TI  - Platelet protein kinase C isoform content in type 2 diabetes complicated with
      retinopathy and nephropathy.
AB  - It has been reported that platelet aggregation in diabetic patients with
      microangiopathy is increased compared with healthy subjects. Chronic
      hyperglycemia is known to cause an increase in diacylglycerol level in various
      tissues. We examine whether protein kinase C (PKC) isoform content in platelets
      from diabetic patients is increased compared with healthy subjects, as previously
      described in the retina, aorta, and heart of diabetic rats. Platelet PKCalpha,
      beta and zeta immunoreactivity in cytosol, membrane and cytoskeleton (CS)
      fractions were analyzed by immunoblotting in 20 type 2 diabetic patients (who had
      been treated with diet alone, sulphonylureas or insulin, and whose condition was
      complicated with retinopathy, nephropathy, neuropathy and/or macroangiopathy) and
      in five healthy subjects. PKCalpha, beta and zeta immunoreactivity in cytosol,
      membrane and CS fractions in platelets from diabetic subjects were not
      significantly higher than those from healthy subjects. However, platelet PKCbeta
      immunoreactivity in cytosol fraction was significantly higher in diabetic
      patients with normal serum creatinine (Cr) level than in diabetic patients with
      abnormal Cr level (Cr > or =1.5 mg/dl) or in healthy subjects. Moreover,
      significant negative correlation between PKCbeta immunoreactivity in cytosol
      fraction of platelets and serum Cr level was found in diabetic patients (P <
      0.05). To clarify the effect of treatment for diabetes, PKC isoform
      immunoreactivity in platelets was measured in type 2 diabetic patients treated
      with diet alone, sulphonylurea or insulin treatment. Serum creatinine level in
      diabetic patients with insulin treatment was significantly higher than in
      diabetic patients with sulphonylurea treatment and diet alone. In addition,
      PKCbeta immunoreactivity in diabetic patients with insulin treatment was
      significantly suppressed compared with that in patients treated by sulphonylurea
      treatment. These results suggest that chronic hyperglycemia may activate platelet
      PKCbeta isoform, and that insulin treatment may decrease platelet PKCbeta
      activity. Finally, not only PKCbeta antagonists, but also glycemic control by
      insulin may prevent development of diabetic microangiopathy.

PMID- 11304415
TI  - Prothrombotic megakaryocyte and platelet changes in hypertension are reversed
      following treatment: a pilot study.
AB  - Platelets are formed from, and their function determined by, bone marrow
      megakaryocytes (MK). Previous studies have found that hypertension is associated
      with accentuated platelet function and that some antihypertensive drug classes
      have antiplatelet activity. We measured MK ploidy (DNA content), size,
      granularity, and expression of the adhesion molecule glycoprotein (GP) IIIa,
      using flow cytometry and measures of platelet function, in 12 untreated
      hypertensive patients and 14 normotensive subjects. Eight hypertensive patients
      were then treated with losartan (50 mg daily), an angiotensin receptor antagonist
      that lowers blood pressure, and MK and platelet parameters re-measured after 6
      weeks. Hypertensive patients had, as compared with matched normotensive subjects:
      increased MK ploidy (mean +/- SD) 22.9 +/- 2.2 N versus 20.8 +/- 1.6 N (2P =
      0.009); increased platelet size, 10.67 +/- 1.03fl versus 9.26 +/- 0.72fl (2P <
      0.001); increased platelet expression of GP IIIa, 108.6 +/- 22.5 versus 92.0 +/-
      12.3 (2P = 0.036); and reduced platelet count, (207 +/- 52) x 10(9)/l versus (257
      +/- 55) x 10(9)/l (2P = 0.026). Losartan significantly reduced MK ploidy, 22.6 +/
      2.2 N versus 21.4 +/- 1.9 N (2P = 0.006); MK size, 607 +/- 22 versus 579 +/- 16
      (2P = 0.003); and lengthened cutaneous bleeding time, 424 +/- 86s versus 563 +/-
      164s (2P = 0.011), in hypertensive patients. Losartan did not alter MK
      granularity or GP IIIa expression, or platelet count, size, mass, GP IIIa
      expression, or aggregation. The data suggest that platelet changes in
      hypertension may be secondary to changes in MKs, and that anti-hypertensive
      treatment can alter MKs and the function of platelets they produce. Since
      antihypertensive therapy reduces the risk of stroke and myocardial infarction,
      MKs are a novel therapeutic target for the prevention of vascular events.

PMID- 11304416
TI  - Differential response of human and bovine platelets to bovine von Willebrand
      factor and vascular subendothelium.
AB  - Human platelets undergo agglutination when stirred with bovine plasma (BP), but
      bovine platelets do not. The present study has shown that exposure of washed
      bovine platelets to subthreshold concentrations of adenosine diphosphate or
      thrombin before stirring restores their sensitivity to BP, and the cells undergo
      rapid agglutination. This agglutination was prevented by a monoclonal antibody,
      to glycoprotein GPIb. Flow cytometry studies revealed that exposure of bovine
      platelets to thrombin caused an increase in their ability to bind antibodies
      known to react with human GPIb or GPIIb-IIIa receptors. Interaction of bovine and
      human platelets with vascular subendothelium revealed additional differences in
      reactivity. Bovine platelets in citrate anticoagulant reacted poorly with
      subendothelium under flow conditions compared with human platelets. In contrast,
      bovine platelets in blood with low molecular weight heparin as anticoagulant
      adhered more readily than human cells. These findings suggest that different
      mechanisms are involved in hemostasis in human and bovine species.

PMID- 11304417
TI  - Pharmacological characterization of cepharanthin in chronic idiopathic
      thrombocytopenic purpura.
AB  - Cepharanthin, a bisbenzylisoquinoline (biscolaurine) alkaloid drug, has been
      reported to improve the symptoms of intractable or steroid-resistant chronic
      idiopathic thrombocytopenic purpura (ITP). To clarify the mechanism by which the
      cepharanthin is beneficial to ITP, we examined the effects of cepharanthin on
      thrombocytopenia in (NZW x BXSB) F1 (W/B F1) mice and on the formation of colony
      forming unit of megakaryocyte (CFU-MK) derived from human CD34-positive
      progenitor cells. The decrease in platelet numbers in W/B F1 was diminished by
      the administration of 5 mg/kg cepharanthin for 6 weeks as well as by 2 mg/kg
      prednisolone. Furthermore, the administration of over 0.2 mg/kg cepharanthin
      enhanced the therapeutic effect of prednisolone. From the data in this animal
      model, it is suggested that cepharanthin may prolong the platelet lifespan. The
      treatment of CD34-positive progenitor cells isolated from cord blood with
      cepharanthin (over 5 x 10(-10)g/ml) caused an increase in the formation of CFU-MK
      induced by the cocktail of thrombopoietin, interleukin (IL)-6 and IL-3. The
      addition of 0.1% normal human serum dramatically increased the number of CFU-MK.
      In contrast, the serum isolated from patients with ITP at the same concentration
      decreased the number of CFU-MK. However, the simultaneous addition of 5 x 10(
      8)g/ml cepharanthin recovered the number of CFU-MK to the level induced by normal
      serum. These findings indicate that cepharanthin has the potent therapeutic
      activity not only on the platelet destruction process, but also on the platelet
      production process of thrombocytopenia in chronic ITP.

PMID- 11304418
TI  - Phospholipids released from activated platelets improve platelet aggregation and
      endothelial cell migration.
AB  - This study was undertaken to isolate phospholipids released from activated
      platelets and to investigate their biological activities. Freshly washed
      platelets were activated with freezing/thawing, thrombin, ionophore 23187, and
      arachidonic acid. Thrombin was incubated with platelet-rich plasma to promote
      synthesis and release of phospholipids from platelets. Phospholipids in
      supernatants of activated platelets were extracted with butanol and separated by
      thin-layer chromatography. Release of phosphatidylserine (PS) and phosphatidic
      acid (PA) increased when platelets were treated with freezing/thawing, ionophore,
      and thrombin. The lysophosphatidyl ethanolamine (LPE) appeared not to be induced
      with freezing/thawing, but increased significantly by thrombin, ionophore, and
      arachidonic acid. The effects of platelet phospholipids on hemostasis and
      angiogenesis were studied with platelet aggregation and endothelium chemotaxis.
      Phospholipids isolated from thrombin-stimulated platelet-rich/platelet-poor
      plasmas were used as synergistic agonists in platelet aggregation and as
      chemotactic agents in endothelial cell migration. Several phospholipids increased
      chemotaxis and platelet aggregation; these were PS, PA, LPE, and sphingosine-1
      phosphate. Also, chemotaxis of those phospholipids increased when combined with
      charcoal-stripped fetal bovine serum, suggesting that cofactors in serum enhanced
      phospholipid-induced cell migration. These observations suggest that activated
      platelets release biologically active phospholipids into the blood stream, where
      they may play an important role in thrombosis and angiogenesis.

PMID- 11304419
TI  - Mean platelet volume is a useful parameter: a reproducible routine method using a
      modified Coulter Thrombocytometer.

PMID- 11304420
TI  - Psychological sub-types among persons with HIV infection: an empirical study.
AB  - Cluster analysis was utilized to derive sub-types from a group of 53 males with
      HIV infection based on scores from several psychological measures. Measures
      administered included the Beck Depression Inventory, Life Orientation Test,
      Rosenberg Self-Esteem Test and the Internal Control Index. Three sub-types were
      identified: (1) average performing sub-type (2) severely dysfunctional sub-type,
      and (3) highly adaptive sub-type. All three sub-types showed different levels and
      patterns of test performance. Results are discussed in terms of sub-type
      characteristics and potential treatment issues.

PMID- 11304421
TI  - The effect of weight loss on body image in HIV-positive gay men.
AB  - The purpose of this study was to assess how body image may be affected by HIV
      related weight loss. Qualitative methodology was used: eight gay men with weight
      loss of at least 10% self-completed a brief, tailor-made questionnaire and then
      participated singly in semi-structured audiotaped interviews. Questionnaire
      analysis showed all but one had avoided social activities in the last two months
      due to self-consciousness over their emaciated appearance; family visits, meeting
      new people and meeting up again with people after weight loss were most
      problematic. Interview analysis revealed that in addition to social
      considerations, bodily comfort and effectiveness were affected, and participants
      identified weight loss as a clear sign of disease progression. Weight regain was
      problematic and food had become a difficult issue for most. These results suggest
      that in gay men, HIV-related weight loss causes significant emotional and
      physical problems.

PMID- 11304422
TI  - Emotional support needs of gay males with AIDS.
AB  - Twenty-five gay and three bisexual males with AIDS (PWAs) rated their needs for
      four different kinds of emotional support (expressing love and concern,
      expressing encouragement and positive feedback, serving as a confidant, and
      providing a philosophical or spiritual perspective) from five different support
      providers (parents, partners, friends, HIV-positive friends and physicians).
      Findings support the importance of emotional support for this population. The
      results indicate that differences exist depending on type and provider of
      support. Participants expressed the greatest need for every category of emotional
      support from partners. Participants also rated their needs from physicians highly
      for each category of emotional support. Noticeably low was the need for providers
      to offer philosophical or spiritual perspectives.

PMID- 11304423
TI  - Assessment of needs of adult symptomatic HIV patients in Hong Kong.
AB  - A cross-sectional survey was designed to assess the physical, psychosocial,
      health behaviour and informational needs of symptomatic HIV patients in Hong
      Kong, using both quantitative and qualitative data collection methods. Forty-six
      consenting adults from an outpatient clinic of a hospital in Hong Kong
      participated in the study. Results showed that up to 67.3% of the sample had
      partially or completely unmet needs in one or more areas of functioning. Major
      needs were related to income, social networking, family processes, money
      management and financial assistance. Only half the sample was satisfied with the
      information received related to their HIV infection and its management. Unsafe
      sexual practices were common, as well as smoking. Meeting these needs through
      policy making or practice could contribute to the enhancement of the quality of
      care and support provided to people living with HIV/AIDS in Hong Kong.

PMID- 11304424
TI  - Hospital services for people with HIV infection in Flanders: patients'
      satisfaction.
AB  - Two questionnaire surveys about satisfaction with hospital services were carried
      out among HIV-infected people in Flanders. In a first survey (CIRCA '93 study)
      between 1993 and 1995, before highly active antiretroviral treatment (HAART) was
      available, questionnaires were distributed by HIV treatment centres, general
      practitioners and HIV support organizations: 315 people with HIV infection
      completed the questionnaire. The level of patient satisfaction was generally
      higher with services at university hospitals than at general hospitals. Most
      patients preferred to be hospitalized in a ward specialized in HIV care. Contact
      with other HIV-infected patients was generally experienced as supportive. The
      second survey included 34 patients with HIV-infection and 83 patients with lung
      disease. They were admitted to the same ward at the Antwerp University Hospital,
      between July 1996 and July 1997. Patients with HIV infections were expecting more
      services than patients with lung disease. Both studies showed that HIV-infected
      patients wanted to be actively involved in diagnostic and treatment decisions.
      The multidisciplinary approach, offered by the Antwerp University Hospital, was
      widely appreciated by patients and could be used as an example for organizing
      patient care for other diseases.

PMID- 11304425
TI  - Alternative medicine use in HIV-positive men and women: demographics, utilization
      patterns and health status.
AB  - Between 1995 and 1997, 1,675 HIV-positive men and women using complementary and
      alternative medicine (CAM) were enrolled into the Bastyr University AIDS Research
      Center's Alternative Medicine Care Outcomes in AIDS (AMCOA) study. Funded by the
      National Institutes of Health (NIH) Office of Alternative Medicine (OAM) and
      National Institute of Allergy and Infectious Diseases (NIAID), the AMCOA study
      collected information on participant demographics, health status and use of
      conventional and CAM therapies. Participants from 46 states completed a baseline
      questionnaire, while additional clinical information (such as CD4 count and HIV
      RNA viral load) was obtained from laboratory records. AMCOA participants reported
      using more than 1,600 different types of CAM therapies (1,210 CAM substances, 282
      CAM therapeutic activities and 119 CAM provider types) for treating HIV/AIDS.
      Approximately two-thirds (63% n = 1,054) of the AMCOA cohort reported using
      antiretroviral drug therapy (ART) during the six-months previous to completing
      the baseline questionnaire, while 37% (n = 621) indicated they were not using
      ART. Of those not using ART, 104 subjects reported never having used any
      conventional medications for their HIV and 12 subjects used only non-prescription
      diarrhoea medications. The most frequently reported CAM substances were vitamin C
      (63%), multiple vitamin and mineral supplements (54%), vitamin E (53%) and garlic
      (53%). CAM provider types most commonly consulted by the AMCOA cohort were
      massage therapists (49%), acupuncturists (45%), nutritionists (37%) and
      psychotherapists (35%). CAM activities most commonly used were aerobic exercise
      (63%), prayer (58%), massage (53%) and meditation (46%). The choice of CAM
      therapies among the AMCOA cohort does not appear to be solely based on scientific
      evidence of efficacy of individual therapies. The majority of AMCOA subjects
      could be characterized as using integrated medicine, since an overwhelming
      proportion of the cohort consult with both conventional and CAM providers and use
      both conventional and CAM medications, yet few subjects reported that their
      conventional and CAM providers work as a team. These data and this cohort set the
      stage for conducting studies of health status changes associated with specific
      CAM therapies.

PMID- 11304426
TI  - HIV infection in families of HIV-positive and 'at-risk' HIV-negative women.
AB  - Research of HIV infection within the family has focused upon sexual partners and
      vertical transmission. The scope of the problem of multiple infections and
      clustering of HIV among family members has, thus far, been less extensively
      explored. The objectives of this study are to investigate HIV infection in family
      members of HIV-seropositive and HIV-seronegative high-risk women and to consider
      the impact of multiple HIV infections within the family. Baseline data were
      evaluated from a prospective observational cohort of 871 HIV-seropositive and 439
      seronegative at-risk women who are participants in a longitudinal study of HIV in
      women at four sites in the USA (Montefiore, Bronx, NY; Johns Hopkins University,
      Baltimore, MD; Brown University, Providence, RI; Wayne State University, Detroit,
      MI). Women were asked if anyone close to them had HIV/AIDS or had died from
      HIV/AIDS. Responses which included HIV-positive family members were analyzed. In
      the seropositive cohort, 35% (307/871) of the women had a family member with HIV
      infection. Of these 307 women, 38% reported having a sibling, 24% a husband and
      27% had more than one family member with HIV/AIDS. Forty-nine per cent of Latina
      women, 34% of black women, and 21% of white women reported having a family member
      with HIV/AIDS. Using logistic regression analysis, we found that Latina and black
      women were significantly more likely than white women to have a sibling, extended
      family member or more than one family member with HIV/AIDS. Compared to
      seropositive women, seronegative high-risk women enrolled in this study appear
      equally likely to have an HIV-infected family member. In this study of HIV
      positive women and high-risk seronegative women, a third reported having multiple
      family members with HIV infection, most often in a sibling. The high prevalence
      of HIV within families, particularly in the families of Latina and black women,
      mandates attention in planning both prevention and care.

PMID- 11304427
TI  - Condom awareness and intended use: gender and religious contrasts among school
      pupils in rural Masaka, Uganda.
AB  - A cross-sectional questionnaire survey examining knowledge, attitudes and
      intended use of condoms was conducted among 1,821 pupils (mean age = 14.2 years,
      range = 9--24) from 27 primary and secondary schools in rural south western
      Uganda. Condom education is not provided in Ugandan schools, but both boys and
      girls had relatively high overall levels of knowledge, even though boys
      demonstrated a higher level than girls. This suggests that respondents had
      successfully obtained reliable information from other sources. Boys and girls had
      similar and fairly positive attitudes towards condoms, although considerable
      shyness was expressed, both about discussing condoms with a partner and buying
      them. Fifty-eight per cent said that they themselves would use a condom if one
      were available, but girls were far less likely than boys to say so. Roman
      Catholics (46% of the sample) were less knowledgeable and less positive about
      condoms than non-Catholics, and the boys in this group, but not the girls, were
      also much less likely to say they would use one. Possible interventions based on
      these findings are discussed, and a research agenda for the delivery of
      assertiveness training to girls is proposed.

PMID- 11304428
TI  - Behavioural surveillance of sexually-related risk behaviours of the Chinese male
      general population in Hong Kong: a benchmark study.
AB  - The objective of the study was to establish a behavioural surveillance system
      (BSS) for sexually-related risk behaviours of the Hong Kong adult male general
      population. Benchmark data were obtained by interviewing 1,020 male respondents,
      age 18 to 60. The results showed that: (1) 14% of the respondents had engaged in
      commercial sex in the past six months, (2) 27% of the male commercial sex clients
      did not always use condoms when having sexual intercourse with commercial sex
      workers (CSWs), (3) 1.5% of the respondents had contracted sexually transmitted
      diseases (STDs) in the past six months, (4) 6.1% of respondents had only ever had
      sex with a man, (5) 0.8% of the respondents had practised unprotected anal
      intercourse with a man in a six-month period, (6) 4.4% of respondents practised
      sexually-related high risk behaviours, defined as unprotected sex with a CSW or
      unprotected anal intercourse with a man, and (7) 36.4% of those who engaged in
      commercial sex had not used condoms with their regular sex partners. Commercial
      sex was often practised outside Hong Kong, very commonly in Mainland China or
      Macau, and was often practised at multiple locations by the same client.
      Effective programmes have to be able to reduce the size of the at-risk
      population. This study together with future ones, will form the first BSS in Hong
      Kong for the general male population and will provide a relevant yardstick for
      programme evaluation.

PMID- 11304429
TI  - Barriers to getting needed services for Ryan White CARE clients.
AB  - To determine why HIV-infected persons do not access needed services, we
      interviewed clients of Ryan White CARE-funded agencies in San Francisco, San
      Mateo and Marin Counties. From July to September 1996, we interviewed 519 clients
      receiving services at 65 CARE-funded sites. Just over half the clients (54.5%)
      had at least one unmet service need in the previous four months; persons in an
      unstable living situation and those with lower perceived health status were
      significantly more likely to have an unmet need. For persons with unmet needs,
      agency barriers were most common (54.0%), followed by emotional issues (44.8%),
      lack of information (44.0%) and financial/practical barriers (19.4%). None of the
      client characteristics (sex, race/ethnicity, age, living situation, perceived
      health status and risk group) were consistently or significantly (p < 0.05)
      associated with specific barriers. We believe that the similarity between clients
      with and without unmet needs reflects the success of CARE in eliminating many
      barriers. However, the persistence of certain barriers and lack of sub-group
      specific barriers suggests the need for individualized interventions to improve
      service delivery, publicize service availability and address the emotional
      barriers to accessing HIV-related care.

PMID- 11304430
TI  - Surgeons' attitudes toward HIV/AIDS in Turkey.
AB  - Currently HIV/AIDS is one of the most difficult challenges for health care
      professionals. As primary medical care providers, attitudes of the physicians
      towards HIV/AIDS are of utmost significance. The aim of this research is to
      determine the attitudes of the surgeons towards HIV/AIDS in their working
      environment. Data were collected from a self-administered questionnaire given to
      128 surgeons. Results revealed that gender, age and professional experience are
      not significant. This study demonstrated that doctors are worried about
      contracting HIV/AIDS from the patients. In some circumstances doctors' attitudes,
      are not clear which may lead to some ethical problems. It is concluded that
      doctors overestimate the risks and they need special education about HIV/AIDS, as
      well as professional help to handle their attitudes toward HIV/AIDS.

PMID- 11304431
TI  - The maintenance of confidentiality in primary care: a survey of policies and
      procedures.
AB  - We investigated policies and procedures for the maintenance of confidentiality in
      primary care by means of a postal survey of 109 general practices in a large non
      metropolitan urban health authority in England. The response rate was 61%.
      Practices believed a variety of staff should be informed if a patient was HIV
      positive, ranging from 'patient's own GP' (100%) to 'clerical staff' (8%). In 88%
      of practices receptionists occasionally or normally asked patients why they
      wished to see a doctor, although in 76% such conversations were audible to other
      patients. Ninety-nine per cent claimed to have a policy on confidentiality,
      although it existed in writing in 62% and was publicized in only 27%. In 88% of
      practices non-clinical staff had access to written patient records. Ninety-three
      per cent provided staff training in confidentiality, but in 34% it was confined
      to induction. Almost all practices had taken some steps to safeguard
      confidentiality, but few had explicit, formal confidentiality policies.
      Information sharing and non-clinical staff access to medical records were
      extensive, and few practices communicated their arrangements to patients.
      Practices need to review their policies and procedures for the maintenance of
      confidentiality.

PMID- 11304433
TI  - UNAIDS/WHO global AIDS statistics.

PMID- 11304434
TI  - Hyperthermic radiosensitization: mode of action and clinical relevance.
AB  - PURPOSE: To provide an update on the recent knowledge about the molecular
      mechanisms of thermal radiosensitization and its possible relevance to
      thermoradiotherapy. SUMMARY: Hyperthermia is probably the most potent cellular
      radiosensitizer known to date. Heat interacts with radiation and potentiates the
      cellular action of radiation by interfering with the cells' capability to deal
      with radiation-induced DNA damage. For ionizing irradiation, heat inhibits the
      repair of all types of DNA damage. Genetic and biochemical data suggest that the
      main pathways for DNA double-strand break (DSB) rejoining, non-homologous end
      joining and homologous recombination, are not the likely primary targets for heat
      induced radiosensitization. Rather, heat is suggested to affect primarily the
      religation step of base excision repair. Subsequently additional DSB arise during
      the DNA repair process in irradiated and heated cells and these additional DSB
      are all repaired with slow kinetics, the repair of which is highly error prone.
      Both mis- and non-rejoined DSB lead to an elevated number of lethal chromosome
      aberrations, finally causing additional cell killing. Heat-induced inhibition of
      DNA repair is considered not to result from altered signalling or enzyme
      inactivation but rather from alterations in higher-order chromatin structure.
      Although, the detailed mechanisms are not yet known, a substantial body of
      indirect and correlative data suggests that heat-induced protein aggregation at
      the level of attachment of looped DNA to the nuclear matrix impairs the
      accessibility of the damaged DNA for the repair machinery or impairs the
      processivity of the repair machinery itself. CONCLUSION: Since recent phase III
      clinical trials have shown significant benefit of adding hyperthermia to
      radiotherapy regimens for a number of malignancies, it will become more important
      again to determine the molecular effects underlying this success. Such
      information could eventually also improve treatment quality in terms of patient
      selection, improved sequencing of the heat and radiation treatments, the number
      of heat treatments, and multimodality treatments (i.e. thermochemoradiotherapy).

PMID- 11304435
TI  - In vivo chromosomal instability and transmissible aberrations in the progeny of
      haemopoietic stem cells induced by high- and low-LET radiations.
AB  - PURPOSE: To study stable and unstable chromosomal aberrations in the haemopoietic
      cells of CBA/H mice after exposure to both high- and low-LET radiations.
      MATERIALS AND METHODS: Chromosomal aberrations were scored in the clonal progeny
      of X-, alpha- or non-irradiated short-term repopulating stem cells using the
      spleen colony-forming unit (CFU-S) assay, 12 days post-transplantation and in the
      bone marrow reconstituted by X-, neutron- or non-irradiated exogenous
      (transplanted) or endogenous (X- or neutron whole-body-irradiated) long-term
      repopulating stem cells for up to 24 months. RESULTS: Chromosomal instability was
      demonstrated in 3-6% of cells in all cases. After transplantation of X- or
      neutron-irradiated bone marrow approximately 8% of cells with stable aberrations
      were recorded at all times. After 3Gy X- or 0.5 Gy neutron- whole-body
      irradiation stable aberrations were detected in approximately 17 and 5% of cells
      respectively. CONCLUSIONS: Chromosomal instability induced in vitro can be
      transmitted in vivo by transplantation of haemopoietic stem cells exposed to high
      or low-LET radiations. Comparable instability can be induced and shown to
      persist for the remaining lifetime after whole-body irradiation. There was no
      direct relationship between the expression of stable and unstable aberrations and
      significant interanimal variation in the expression of both stable and unstable
      aberrations.

PMID- 11304436
TI  - Exchange aberrations among 11 chromosomes of human lymphocytes induced by gamma
      rays.
AB  - PURPOSE: To detect the frequencies of interchanges among 11 chromosomes in
      lymphocytes irradiated with gamma-rays and to find out whether these frequencies
      reflect the proximity of some of these chromosomes within the interphase nucleus.
      MATERIAL AND METHODS: Exchange aberrations were detected in the first mitosis
      after irradiation of human lymphocytes with 3 and 5 Gy gamma-rays of 60Co. Two
      colour repeated FISH with two differently chemically modified probes in each
      hybridization was applied. The microscope stage positions of each mitosis were
      recorded after the first hybridization and used for the automatic scanning of
      images after all successive experiments. Five images were obtained for each
      mitosis differing in visualized pairs of chromosomes. Comparing these images,
      exchanges among 10 chromosomes could be detected. Painting of the p arm of
      chromosome 21 with the painting probe for chromosome 22 also made it possible to
      detect exchanges of this chromosome with other chromosomes of the selected group.
      RESULTS: Frequencies of exchange aberrations induced in chromosomes of the
      selected group as well as interchanges between many pairs of chromosomes of this
      group were roughly proportional to the DNA content of chromosomes. Higher
      frequencies of interchanges than expected according to the model of linear
      proportionality were found between several chromosomes involved in translocations
      frequent in different subtypes of leukaemia. CONCLUSIONS: Frequencies of
      interchanges among 11 chromosomes of human lymphocytes induced by gamma-rays do
      not indicate as clearly as fast neutrons the non-random arrangement of
      chromosomes in the cell nucleus. The interaction of a large number of chromosomes
      in exchange aberrations suggests that the chromatin in the territory of one
      chromosome is accessible for several other chromosomes.

PMID- 11304437
TI  - Comparison of the risks of cancer incidence and mortality following radiation
      therapy for benign and malignant disease with the cancer risks observed in the
      Japanese A-bomb survivors.
AB  - PURPOSES: To compare the radiation-associated relative risks of cancer incidence
      and mortality in groups exposed to ionizing radiation in the course of treatment
      for a variety of malignant and non-malignant conditions with those in the
      Japanese A-bomb survivor cancer incidence and mortality data. MATERIALS AND
      METHODS: Comparison of the excess relative risk coefficients derived from
      published information for each study with the excess relative risk coefficient in
      comparable (age at exposure, time since exposure, sex) matched subsets of the
      Japanese A-bomb survivor cancer incidence and mortality data. RESULTS: Sixty-five
      studies of persons who have received appreciable doses of ionizing radiation in
      the course of treatment and for whom there is adequate ascertainment of cancer
      incidence or mortality are identified, from which 116 cancer-site-specific
      estimates of excess relative risk are derived. Relative risks tend to be lower in
      the medical series than in the Japanese A-bomb survivors. The most marked
      discrepancies between the relative risks in the medical series and in the A-bomb
      survivors are for leukaemia, where 12 of the 17 medical studies have
      significantly lower relative risks than those observed in the Japanese data.
      However, the ratio between the relative risks in the medical studies and in the
      Japanese data tends to diminish with increasing average or maximal therapy dose.
      This is observed for all cancer sites and is particularly marked for leukaemia.
      After taking account of cell sterilization and dose fractionation the apparent
      differences between the relative risks for leukaemia in the Japanese A-bomb
      survivors and in the medical series largely disappear. This suggests that cell
      sterilization largely accounts for the discrepancy between the relative risks in
      the Japanese data and the medical studies. Other factors, such as the differences
      in underlying cancer risks between the Japanese A-bomb survivors and the medical
      series, and dose-fractionation effects, may also contribute. CONCLUSIONS: The
      relative risks of cancer in studies of persons exposed to appreciable doses of
      ionizing radiation in the course of treatment for a variety of malignant and non
      malignant conditions are generally less than those in comparable subsets of the
      Japanese A-bomb survivor cancer incidence and mortality data. Cell sterilization
      effects can largely explain the discrepancy between the Japanese and the medical
      series.

PMID- 11304438
TI  - Characteristic association between K-ras gene mutation with loss of
      heterozygosity in X-ray-induced thymic lymphomas of the B6C3F1 mouse.
AB  - PURPOSE: To elucidate the characteristics of radiation carcinogenesis, the
      spectra of K- and N-ras oncogene mutations, loss of heterozygosity (LOH) and
      their association in X-ray-induced thymic lymphomas (TL) were determined by
      comparing with those of N-ethyl-N-nitrosourea (ENU)-induced and spontaneously
      occurring TL. MATERIALS AND METHODS: TL that arose in untreated, X-ray-irradiated
      and ENU-treated B6C3F1 mice were examined both for K- and N-ras mutations by PCR
      SSCP and DNA sequencing and for LOH by PCR with polymorphic microsatellite
      markers. RESULTS: (1) ras gene mutations were found in a proportion of TL from X
      ray-exposed (approximately 20%) and ENU-treated (30-40%) mice while no ras gene
      mutations were found in spontaneous TL. N-ras mutations were rare. (2) The
      spectrum of ras gene mutations was diverse and seemed to differ little between X
      ray-induced and ENU-induced TL, even though there was a higher frequency of ras
      mutations in ENU-induced TL that clustered to K-ras codon 12. (3) The X-ray
      induced TL showing K-ras mutation were associated with LOH on chromosome 6, while
      those showing no K-ras mutation were associated with high frequency of LOH on
      chromosomes 4, 11 and 12. CONCLUSION: These results demonstrate that, in the
      B6C3F1 mouse TL, X-ray-induced lymphomagenesis showed both the co-expression, yet
      low occurrence of allelic imbalance on chromosome 6 and K-ras mutation, and
      exclusive expression of frequent allelic imbalance on chromosomes 4, 11 and 12
      and K-ras mutation.

PMID- 11304439
TI  - Persistent subclinical inflammation among A-bomb survivors.
AB  - PURPOSE: To investigate the associations between inflammation tests and radiation
      dose in A-bomb survivors. SUBJECTS AND METHODS: Subjects were A-bomb survivors
      who underwent inflammation tests of leukocyte counts, neutrophil counts,
      erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, alpha-1
      globulin, alpha-2 globulin and sialic acid between 1988 and 1992. Associations
      with radiation dose (DS86) were analyzed by regression analysis and heterogeneity
      among inflammatory diseases, anaemia at examination, or history of cancer was
      also tested. RESULTS: The associations with radiation dose were statistically
      significant for leukocyte counts (71.0mm(-3) Gy(-1), p=0.015), erythrocyte
      sedimentation rate (1.58 mm h(-1) Gy(-1) , p = 0.0001), corrected erythrocyte
      sedimentation rate (1.14mm h(-1) Gy(-1), p=0.0001), alpha-1 globulin (0.0057 g
      dl(-1) Gy(-1), p=0.0001), alpha-2 globulin (0.0128 g dl(-1) Gy(-1), p=0.0001),
      and sialic acid (1.2711 mg dl(-1) Gy(-1), p=0.0001) but not for neutrophil counts
      (29.9 mm(-3) Gy(-1), p=0.17). Heterogeneity was not statistically significant.
      Among inflammatory diseases, associations were the strongest for chronic
      thyroiditis and chronic liver diseases. CONCLUSIONS: This study suggests
      statistically significant association between inflammation in A-bomb survivors
      and radiation dose of during 1988-1992. The association might contribute, as an
      epigenetic and/or bystander effect, to development of several radiation-induced
      disorders.

PMID- 11304440
TI  - Effects of 50 Hz magnetic fields on cancer induced by ionizing radiation in mice.
AB  - PURPOSE: To evaluate the effects of 50 Hz magnetic fields (MF) on the development
      of cancer induced by ionizing radiation. MATERIALS AND METHODS: A total of 150
      female CBA/S mice were randomized into three equal groups at the age of 3-5
      weeks. One of the groups served as a 'cage-control group'. The two other groups
      were exposed to ionizing radiation in the beginning of the study. One of these
      two groups was exposed 24 h per day, for 1.5 years, to a 50Hz vertical MF, the
      intensity of which varied regularly between 1.3, 13 and 130 muT. The other served
      as a control group and was sham-exposed to MF in similar, but unenergized,
      exposure racks. Body weights, clinical signs, and food and water consumption were
      recorded regularly. Haematological examination, and the histopathological
      analysis of all lesions and major tissues were performed on all animals. RESULTS:
      MF exposure did not increase the incidence of any primary neoplasms. However, the
      incidence of basophilic liver foci, a probable pre-neoplastic change in liver,
      was increased. The incidence of hepatocellular adenomas was unchanged, whereas
      the incidence of hepatocellular carcinomas was slightly, but not statistically
      significantly, elevated. CONCLUSIONS: It is concluded that overall the results of
      this study do not support a role for MF as a tumour promoter.

PMID- 11304441
TI  - A mathematical model for cell density and proliferation in squamous epithelium
      after single-dose irradiation.
AB  - PURPOSE: To establish a mathematical model describing changes in cell density in
      squamous epithelia induced by single-dose irradiation. Detailed data from
      previous studies in mouse tongue epithelium have been used for this study.
      MATERIALS AND METHODS: The major mechanisms of the epithelial regeneration
      response, i.e. loss of division asymmetry and accelerated proliferation of stem
      cells, in combination with residual, abortive proliferation of sterilized cells,
      have been included in a tissue compartment model. These phenomena have been
      incorporated via three parameters; T(delay), the duration of the cell cycle
      block; T(min), the minimum stem cell cycle time due to acceleration; and T(stop),
      the duration of abortive proliferation. The compartments introduced in the model
      are normal stem cells, S1; sterilized stem cells, S2; and post-mitotic,
      functional cells, F. The flux rats between the tissue compartments were defined
      by autoregulation of the stem cell population, and by overall cell numbers. The
      model was applied to fit experimental data on changes in oral mucosal cell
      density after single-dose exposure with 13 and 20 Gy. The best-fit sets of
      parameters were identified by L2 norm error analysis based on the total cell
      count. RESULTS: For 13 Gy, the best fit was achieved with T(min) = 1.0 days,
      T(delay) = 1.2 days and T(stop) = 7.5 days. For 20 Gy, the parameters were,
      T(min) =0.7 days, T(delay)= 1.0 days and T(stop) =9.5 days. In both data sets,
      T(min) was the most influential parameter. The resulting fluctuations in stem
      cell numbers were in good accordance with changes in radiation tolerance after 13
      Gy. CONCLUSIONS: The model can be used to define dose-dependent parameters
      describing the morphological response of squamous epithelia to single-dose
      irradiation. Based on these parameters, post-irradiation fluctuations in
      radiosensitivity can be predicted. For developing more complex and reliable
      mathematical models, which could incorporate transit divisions or fractionated
      radiotherapy, further experimental data at various dose levels are required.

PMID- 11304442
TI  - Effectiveness of radiolabelled antibodies for radio-immunotherapy in a colorectal
      xenograft model: a comparative study using the linear--quadratic formulation.
AB  - PURPOSE: To develop a model that relates the pattern of dose delivery during
      radio-immunotherapy to biological effect. This model was used to assess the
      efficacy of a range of antibodies labelled with 131I, 186Re and 90Y. MATERIALS
      AND METHODS: Pharmacokinetic data were obtained by injecting tumour-bearing nude
      mice with radiolabelled antibody. The dose-rate in bone marrow and tumour was
      then given by a two-compartment model description of the pharmacokinetics
      combined with the radionuclide properties. Response characteristics of tumour and
      marrow were defined in terms of radiosensitivity, repair capacity and
      proliferation, and the biological effect was assessed using the linear quadratic
      formulation. RESULTS: Tumour-specific antibodies with intermediate molecular
      weight and clearance from the circulation delivered the most effective doses to
      tumour due to their rapid uptake and prolonged retention in tumour coupled with
      efficient clearance from blood. Matching the radionuclide with antibody
      pharmacokinetics and tumour type further increased this effect. CONCLUSIONS: The
      model improves conceptual understanding of the relationship of parameters
      affecting therapy and makes it possible to optimize radio-immunotherapy by
      selecting the most effective antibody and radionuclide according to tumour
      biology.

PMID- 11304443
TI  - Significance of cell-cycle delay, multiple initiation pathways, misrepair and
      replication errors in a model of radiobiological effects.
AB  - PURPOSE: To advance a biomathematical model of radiocarcinogenesis by describing
      multiple pathways for initiation, a radiologically induced cell-cycle delay,
      misrepair and spontaneous DNA damages caused by replication. It was investigated
      whether the incorporation of these biological features would improve the fit of
      the model to data showing plateaus in in vitro irradiations of different cell
      lines and whether the fit parameters were then more biologically realistic.
      MATERIALS AND METHODS: A biomathematical submodel was developed based on a
      previous State-Vector Model that mathematically described enhanced DNA repair and
      radical scavenging following irradiation. RESULTS: With the two initiation
      pathways and cell-cycle delay, the simulations better explained the mouse data
      but not the rat data, and for both data sets the fit parameters were biologically
      more realistic than previously assumed. Inclusion of misrepair and replicational
      errors did not significantly affect the fit. CONCLUSIONS: A plateau in the dose
      effect relationship for in vitro irradiation of different cell lines can be
      explained by radioprotective mechanisms. The plateau-type dose-response
      relationships point to a non-linear dose- effect relationship at low doses and
      indicate that linear extrapolation from moderate (or high) to low doses may not
      be justified for in vitro studies of these cell lines.

PMID- 11304444
TI  - High sensitivity of rat foetal germ cells to low dose-rate irradiation.
AB  - PURPOSE: To investigate the response of germ and Sertoli cells to gamma
      irradiation at two distinct periods of testicular development in rat foetuses.
      MATERIALS AND METHODS: Pregnant rats were exposed to 60Co gamma-rays at days 15,
      19 or 21 post-coitum (p.c.), at doses ranging from 0.1 to 1.5Gy, and at different
      dose-rates. Testicular weight, seminiferous tubule condition and the number of
      germ and Sertoli cells were measured at early and late times after irradiation.
      Apoptosis was studied by the ISEL method and p53 expression was studied by
      immunohistochemistry. RESULTS: At high dose-rates (> or = 3.3 Gy min(-1)), 1.5 Gy
      radiation at day 15 p.c. had a short-term effect on germ cell survival. A large
      proportion of these cells rapidly underwent p53-independent apoptosis. Apoptotic
      cells were strongly clustered. The remaining germ cells divided and
      differentiated normally leading to a majority of normal tubules in the adult
      testis. However, at low dose-rate (0.6mGy min(-1)), much greater depopulation of
      the seminiferous tubules occurred. When irradiation was given at day 19 p.c., the
      same dose had a delayed effect on germ cells, leading to sterility. Sertoli cells
      had a normal survival for irradiation at day 15 p.c. Their proliferation became
      higher in prepubescent testis compared with controls, when irradiation occurred
      at day 19 p.c. CONCLUSION: The position of gonocytes in the cell cycle at the
      time of irradiation seems to be a determining parameter for inducing gonocyte
      apoptosis. The strong effect of irradiation on germ cells at very low dose-rate
      and the appearance of clusters of apoptotic gonocytes may be a consequence of the
      syncitial organization of germ cells, favouring their cell synchronisation or the
      transmission of death signalling when they are in a radiosensitive period.

PMID- 11304448
TI  - Toward tissue engineering of the knee meniscus.
AB  - This review details current efforts to tissue engineer the knee meniscus
      successfully. The meniscus is a fibrocartilaginous tissue found within the knee
      joint that is responsible for shock absorption, load transmission, and stability
      within the knee joint. If this tissue is damaged, either through tears or
      degenerative processes, then deterioration of the articular cartilage can occur.
      Unfortunately, there is a dearth in the amount of work done to tissue engineer
      the meniscus when compared to other musculoskeletal tissues, such as bone. This
      review gives a brief overview of meniscal anatomy, biochemical properties,
      biomechanical properties, and wound repair techniques. The discussion centers
      primarily on the different components of attempting to tissue engineer the
      meniscus, such as scaffold materials, growth factors, animal models, and
      culturing conditions. Our approach for tissue engineering the meniscus is also
      discussed.

PMID- 11304449
TI  - A new strategy to produce sustained growth of central nervous system axons:
      continuous mechanical tension.
AB  - Although a primary strategy to repair spinal cord and other nerve injuries is to
      bridge the damage with axons, producing axons of sufficient length and number has
      posed a significant challenge. Here, we explored the ability of integrated
      central nervous system (CNS) axons to grow long distances in response to
      continuous mechanical tension. Neurons were plated on adjacent membranes and
      allowed to integrate, including the growth of axons across a 50-microm border
      between the two membranes. Using a microstepper motor system, we then
      progressively separated the two membranes further apart from each other at the
      rate of 3.5 microm every 5 min. In the expanding gap, we found thick bundles
      comprised of thousands of axons that responded to this tensile elongation by
      growing a remarkable 1 cm in length by 10 days of stretch. This is the first
      evidence that the center portion of synapsed CNS axons can exhibit sustained
      "stretch-induced growth." This may represent an important growth mechanism for
      the elongation of established white matter tracts during development. We also
      found by doubling the stretch rate to 7 microm/5 min that the axon bundles could
      not maintain growth and disconnected in the center of the gap by 3 days of
      stretch, demonstrating a tolerance limit for the rate of axonal growth. We
      propose that this newfound stretch-induced growth ability of integrated CNS axons
      may be exploited to produce transplant materials to bridge extensive nerve
      damage.

PMID- 11304450
TI  - Two-dimensional manipulation of cardiac myocyte sheets utilizing temperature
      responsive culture dishes augments the pulsatile amplitude.
AB  - Although cardiac myocytes adherent to tissue culture polystyrene (TCPS) dishes
      retain the spontaneous beating, the pulsatile amplitude is highly limited
      compared to that in vivo. One of the main reasons for the limited pulsation may
      be the interface between the cells and the TCPS surfaces. Release of these cells
      from rigid TCPS surfaces may augment their pulsatile amplitude. With this
      perspective, we have developed a novel cell manipulation technique to detach
      cultured cardiac myocytes from rigid surfaces and to rescue higher pulsatile
      amplitude of the cells using temperature-responsive culture dishes and discuss
      the possibility of improving this heart tissue model. Primary cardiac myocytes
      were cultured on the slightly hydrophobic dish surfaces grafted with a
      temperature-responsive polymer, poly(N-isopropylacrylamide). Cells adhered and
      proliferated, forming confluent cardiac myocyte sheets in a fashion similar to
      those on ungrafted TCPS dishes. Decrease in culture temperature resulted in
      surface change of the polymer from slight hydrophobic to highly hydrophilic due
      to extensive hydration of the grafted polymer on the dishes. This results in
      release of cardiac myocyte sheets from the dishes without enzymatic or EDTA
      treatment. When no support was used, the detached cardiac myocyte sheets shrank
      to one-tenth size, which ceased their pulsation. When chitin membranes were used
      to support the confluent sheets to prevent cell shrinkage, the detached cell
      sheets could be transferred and readily adhered onto another virgin TCPS dishes.
      These transferred cell sheets preserved the similar cell morphology and pulsation
      to those before the detachment. When polyethylene meshes were used to support
      cell sheet transfer, detached cardiac myocyte sheets partially attached to the
      mesh threads. Then, the constructs were inverted and placed in another culture
      dish to prevent direct association to dish surfaces. Moreover, the cardiac
      myocyte sheets were reorganized to heart tissue-like structures by the
      unisotropic contraction orientated by the mesh threads, and the pulsatile
      amplitude increased more than 10 times higher. This technique would bring about
      new insight in tissue engineering as well as cultured heart model.

PMID- 11304451
TI  - Muscle prelamination with urothelial cell cultures via fibrin glue in rats.
AB  - The purpose of the study was to transplant autologous cultured urothelial cells
      onto a muscle via fibrin glue as a delivery vehicle to create a vascularized,
      living matrix lined with urothelium that could subsequently be used for urinary
      reconstruction. Bladder tissue specimens from male Wistar rats (n = 32; 350--500
      g) were harvested for urothelial tissue culture. After 8--10 days when the
      primary cultures became confluent, the cultured urothelial cells were injected
      underneath the rectus sheath onto the rectus muscle. As delivery vehicle we
      compared standard culture media and fibrin glue. At 1- and 4-week intervals
      following urothelial cell grafting, sections of the muscle were analyzed for
      urothelial graft take using Hematoxylin & Eosin and immunohistochemical staining.
      The histology demonstrated viable, multilayered clusters of urothelium cells on
      the muscle surface only in the group using the fibrin glue delivery vehicle. We
      conclude that a muscle can be successfully prelaminated with autologously
      cultured urothelial cells via fibrin glue and has therefore potential for urinary
      reconstructions.

PMID- 11304452
TI  - Demineralized bone matrix as a biological scaffold for bone repair.
AB  - Experimental models were created in rat fibula to represent impaired bone healing
      so that biological deficiencies that cause bone repair to fail or to be delayed
      may be investigated. These models consist of a 4-mm-long segmental defect,
      created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen
      of demineralized bone matrix (DBM) over the cut ends of the fibula. The
      experiments in this study involved various modifications of the DBM scaffold
      designed to reduce its osteoinductive activity: steam sterilization (sDBM),
      ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine
      hydrochloride extraction (gDBM). Bone healing was evaluated by bending rigidity
      of the fibula and mineral content of the repair site at 7 weeks post-surgery. The
      sDBM scaffolds resorbed completely by 7 weeks and hence this model was a
      nonhealing negative control. Rigidities in the unmodified DBM and tDBM groups
      were comparable, whereas in the gDBM and eoDBM groups it was significantly
      reduced. Histologically, in the 4-mm defects repaired with unmodified DBM, direct
      and endochondral bone formation in the scaffold and the defect resulted in a
      neocortex consisting of woven and lamellar bone uniting the broken bone by 7
      weeks post-surgery. We conclude that the eoDBM and gDBM groups represent failure
      or delay of the bone repair process when compared with the unmodified DBM group
      in which the process is analogous to normal bone healing.

PMID- 11304453
TI  - Aggregation enhances catecholamine secretion in cultured cells.
AB  - Transplanted cells and tissues have potential uses in the treatment of genetic,
      geriatric, and metabolic disorders, but optimal conditions for transplantation
      are not yet known. In this report, PC12 cells were aggregated in rotary and
      microgravity culture, using serum-free or serum-supplemented medium, and using a
      multifunctional polymer-peptide aggregation factor. Aggregates and single cells
      were then encapsulated and cultured within agarose gels, and the dopamine
      secretion in response to a depolarization buffer was measured using high
      performance liquid chromatography combined with electrochemical detection (HPLC
      ECD). On a per-cell basis, aggregated cells secreted higher levels of dopamine
      than did single cells. The size of the aggregates was also a factor in
      catecholamine secretion; dopamine release from the larger aggregates formed in
      rotary culture was observed to increase at a faster rate, then achieve a plateau
      level at an earlier time than did the smaller aggregates. Cells aggregated in
      microgravity culture exhibited a markedly different behavior, lacking the rapid
      rise in dopamine secretion characteristic of the rotary-aggregates cells: on a
      per-cell basis, the dopamine secretion remained at a level corresponding to the
      plateau level expressed by the rotary-aggregates cells. Dopamine secretion in
      aggregates may be enhanced by the increase in number of cell-cell contacts, as
      occurs during high-density culture of PC12 cells. These results provide further
      evidence that cell-cell contact regulates the behavior of differentiated cells,
      and therefore is important in tissue engineering.

PMID- 11304454
TI  - Two-photon laser scanning microscopy of epithelial cell-modulated collagen
      density in engineered human lung tissue.
AB  - Tissue remodeling is a complex process that can occur in response to a wound or
      injury. In lung tissue, abnormal remodeling can lead to permanent structural
      changes that are characteristic of important lung diseases such as interstitial
      pulmonary fibrosis and bronchial asthma. Fibroblast-mediated contraction of three
      dimensional collagen gels is considered an in vitro model of tissue contraction
      and remodeling, and the epithelium is one factor thought to modulate this
      process. We studied the effects of epithelium on collagen density and contraction
      using two-photon laser scanning microscopy (TPLSM). TPLSM was used to image
      autofluorescence of collagen fibers in an engineered tissue model of the human
      respiratory mucosa -- a three-dimensional co-culture of human lung fibroblasts
      (CCD-18 lu), denatured type I collagen, and a monolayer of human alveolar
      epithelial cell line (A549) or human bronchial epithelial cell line (16HBE14o(
      )). Tissues were imaged at days 1, 8, and 15 at 10 depths within the tissue. Gel
      contraction was measured concurrently with TPLSM imaging. Image analysis shows
      that gels without an epithelium had the fastest rate of decay of fluorescent
      signal, corresponding to highest collagen density. Results of the gel contraction
      assay show that gels without an epithelium also had the highest degree of
      contraction (19.8% +/- 4.0%). We conclude that epithelial cells modulate collagen
      density and contraction of engineered human lung tissue, and TPLSM is an
      effective tool to investigate this phenomenon.

PMID- 11304455
TI  - Evaluation of nanostructured composite collagen--chitosan matrices for tissue
      engineering.
AB  - The development of suitable three-dimensional matrices for the maintenance of
      cellular viability and differentiation is critical for applications in tissue
      engineering and cell biology. The structure and composition of the extracellular
      matrix (ECM) has been shown to modulate cell behavior with respect to shape,
      movement, proliferation, and differentiation. Although collagen and chitosan have
      separately been proposed as in vitro ECM materials, the influence of chitosan-
      collagen composite matrices on cell morphology, differentiation, and function is
      not well studied. To this end, gel matrices of different proportions of collagen
      and chitosan were examined ultrastructurally and characterized for their ability
      to regulate cellular activity. A three-chamber system with circulating hydraulic
      fluids was used to evaluate the gel stability under fluid force. Results
      indicated that overall matrix integrity increased with the proportion of
      chitosan. Scanning electron microscopy indicated that the addition of chitosan
      greatly influences ultrastructure and changes collagen fiber cross-linking,
      reinforcing the structure and increasing pore size. K562 cells cultured in three
      dimensional gels were examined for cell proliferation and differentiation.
      Although cell proliferation was inhibited with an increasing proportion of
      chitosan, cell function based on cytokine-release was greatly augmented. Results
      suggest that a hybrid chitosan--collagen matrix may have potential biological and
      mechanical benefits for use as a cellular scaffold.

PMID- 11304456
TI  - Multilineage cells from human adipose tissue: implications for cell-based
      therapies.
AB  - Future cell-based therapies such as tissue engineering will benefit from a source
      of autologous pluripotent stem cells. For mesodermal tissue engineering, one such
      source of cells is the bone marrow stroma. The bone marrow compartment contains
      several cell populations, including mesenchymal stem cells (MSCs) that are
      capable of differentiating into adipogenic, osteogenic, chondrogenic, and
      myogenic cells. However, autologous bone marrow procurement has potential
      limitations. An alternate source of autologous adult stem cells that is
      obtainable in large quantities, under local anesthesia, with minimal discomfort
      would be advantageous. In this study, we determined if a population of stem cells
      could be isolated from human adipose tissue. Human adipose tissue, obtained by
      suction-assisted lipectomy (i.e., liposuction), was processed to obtain a
      fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA
      cells can be maintained in vitro for extended periods with stable population
      doubling and low levels of senescence. Immunofluorescence and flow cytometry show
      that the majority of PLA cells are of mesodermal or mesenchymal origin with low
      levels of contaminating pericytes, endothelial cells, and smooth muscle cells.
      Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic,
      myogenic, and osteogenic cells in the presence of lineage-specific induction
      factors. In conclusion, the data support the hypothesis that a human lipoaspirate
      contains multipotent cells and may represent an alternative stem cell source to
      bone marrow-derived MSCs.

PMID- 11304457
TI  - Is paraoxonase-3 another hdl-associated protein protective against
      atherosclerosis?

PMID- 11304458
TI  - Familial combined hyperlipidemia and insulin resistance : distant relatives
      linked by intra-abdominal fat?

PMID- 11304459
TI  - Role of reactive oxygen species in angiotensin ii signaling : the plot thickens.

PMID- 11304460
TI  - Paraoxonase and atherosclerosis.
AB  - There is considerable evidence that the antioxidant activity of high density
      lipoprotein (HDL) is largely due to the paraoxonase-1 (PON1) located on it.
      Experiments with transgenic PON1 knockout mice indicate the potential for PON1 to
      protect against atherogenesis. This protective effect of HDL against low density
      lipoprotein (LDL) lipid peroxidation is maintained longer than is the protective
      effect of antioxidant vitamins and could thus be more important. There is
      evidence that the genetic polymorphisms of PON1 least able to protect LDL against
      lipid peroxidation are overrepresented in coronary heart disease, particularly in
      association with diabetes. However, these polymorphisms explain only part of the
      variation in serum PON1 activity; thus, a more critical test of the hypothesis is
      likely to be whether low serum PON1 activity is associated with coronary heart
      disease. Preliminary case-control evidence suggests that this is indeed the case
      and, thus, that the quest for dietary and pharmacological means of modifying
      serum PON1 activity may allow the oxidant model of atherosclerosis to be tested
      in clinical trials.

PMID- 11304461
TI  - HDL and the inflammatory response induced by LDL-derived oxidized phospholipids.
AB  - Oxidation of low density lipoprotein (LDL) phospholipids containing arachidonic
      acid at the sn-2 position occurs when a critical concentration of "seeding
      molecules" derived from the lipoxygenase pathway is reached in LDL. When this
      critical concentration is reached, the nonenzymatic oxidation of LDL
      phospholipids produces a series of biologically active, oxidized phospholipids
      that mediate the cellular events seen in the developing fatty streak. Normal high
      density lipoprotein (HDL) contains at least 4 enzymes as well as apolipoproteins
      that can prevent the formation of the LDL-derived oxidized phospholipids or
      inactivate them after they are formed. In the sense that normal HDL can prevent
      the formation of or inactivate these inflammatory LDL-derived oxidized
      phospholipids, normal HDL is anti-inflammatory. HDL from mice that are
      genetically predisposed to diet-induced atherosclerosis became proinflammatory
      when the mice are fed an atherogenic diet, injected with LDL-derived oxidized
      phospholipids, or infected with influenza A virus. Mice that were genetically
      engineered to be hyperlipidemic on a chow diet and patients with coronary
      atherosclerosis, despite normal lipid levels, also had proinflammatory HDL. It is
      proposed that LDL-derived oxidized phospholipids and HDL may be part of a system
      of nonspecific innate immunity and that the detection of proinflammatory HDL may
      be a useful marker of susceptibility to atherosclerosis.

PMID- 11304462
TI  - Epidermal growth factor receptor transactivation by angiotensin II requires
      reactive oxygen species in vascular smooth muscle cells.
AB  - Angiotensin II (Ang II) is a vasoactive hormone with critical roles in vascular
      smooth muscle cell growth, an important feature of hypertension and
      atherosclerosis. Many of these effects are dependent on the production of
      reactive oxygen species (ROS). Ang II induces phosphorylation of the epidermal
      growth factor (EGF) receptor (EGF-R), which serves as a scaffold for various
      signaling molecules. Here, we provide novel evidence that ROS are critical
      mediators of EGF-R transactivation by Ang II. Pretreatment of vascular smooth
      muscle cells with the antioxidants diphenylene iodonium, Tiron, N-acetylcysteine,
      and ebselen significantly inhibited ( approximately 80% to 90%) tyrosine
      phosphorylation of the EGF-R by Ang II but not by EGF. Of the 5
      autophosphorylation sites on the EGF-R, Ang II mainly phosphorylated Tyr1068 and
      Tyr1173 in a redox-sensitive manner. The Src family kinase inhibitor PP1,
      overexpression of kinase-inactive c-Src, or chelation of intracellular Ca(2+)
      attenuated EGF-R transactivation. Although antioxidants had no effects on the
      Ca(2+) mobilization or phosphorylation of Ca(2+)-dependent tyrosine kinase Pyk2,
      they inhibited c-Src activation by Ang II, suggesting that c-Src is 1 signaling
      molecule that links ROS and EGF-R phosphorylation. Furthermore, Ang II-induced
      tyrosine phosphorylation of the autophosphorylation site and the SH2 domain of c
      Src was redox sensitive. These findings emphasize the importance of ROS in
      specific Ang II-stimulated growth-related signaling pathways and suggest that
      redox-sensitive EGF-R transactivation may be a potential target for antioxidant
      therapy in vascular disease.

PMID- 11304463
TI  - Reactive oxygen species mediate endothelium-dependent relaxations in
      tetrahydrobiopterin-deficient mice.
AB  - (6R)-5,6,7,8-Tetrahydro-biopterin (H(4)B) is essential for the catalytic activity
      of all NO synthases. The hyperphenylalaninemic mouse mutant (hph-1) displays 90%
      deficiency of the GTP cyclohydrolase I, the rate-limiting enzyme in H(4)B
      synthesis. A relative shortage of H(4)B may shift the balance between endothelial
      NO synthase (eNOS)-catalyzed generation of NO and reactive oxygen species.
      Therefore, the hph-1 mouse represents a unique model to assess the effect of
      chronic H(4)B deficiency on endothelial function. Aortas from 8-week-old hph-1
      and wild-type mice (C57BLxCBA) were compared. H(4)B levels were determined by
      high-performance liquid chromatography and NO synthase activity by
      [(3)H]citrulline assay in homogenized tissue. Superoxide production by the
      chemiluminescence method was measured. Isometric tension was continuously
      recorded. The intracellular levels of H(4)B as well as constitutive NO synthase
      activity were significantly lower in hph-1 compared with wild-type mice. Systolic
      blood pressure was increased in hph-1 mice. However, endothelium-dependent
      relaxations to acetylcholine were present in both groups and abolished by
      inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester as well. Only
      in hph-1 mice were the relaxations inhibited by catalase and enhanced by
      superoxide dismutase. After incubation with exogenous H(4)B, the differences
      between the 2 groups disappeared. Our findings demonstrate that H(4)B deficiency
      leads to eNOS dysfunction with the formation of reactive oxygen species, which
      become mediators of endothelium-dependent relaxations. A decreased availability
      of H(4)B may favor an impaired activity of eNOS and thus contribute to the
      development of vascular diseases.

PMID- 11304464
TI  - Network of vascular-associated dendritic cells in intima of healthy young
      individuals.
AB  - In earlier studies, our group has established a new "immunological" hypothesis
      for atherogenesis supported by experimental and clinical studies showing that
      inflammatory immunological reactions against heat shock protein 60 initiate the
      development of atherosclerosis. In the present study, we describe the discovery
      of a so-far-unknown network of dendritic cells in the innermost layer of
      arteries, the intima, but not veins of healthy humans and rabbits. The number of
      these dendritic cells is comparable to that of Langerhans cells in the skin, and
      dendritic cells show a similar phenotype (CD1a(+) S-100(+) lag(+) CD31(-) CD83(-)
      CD86(-) and no staining for von Willebrand factor or smooth muscle cell myosin).
      These vascular-associated dendritic cells accumulate most densely in those
      arterial regions that are subjected to major hemodynamic stress by turbulent flow
      conditions and are known to be predisposed for the later development of
      atherosclerosis. These results open new perspectives for the activation of the
      immune system within the arterial wall.

PMID- 11304465
TI  - Myosin light chain kinase regulates capacitative ca(2+) entry in human
      monocytes/macrophages.
AB  - Monocytes/macrophages are present in all stages of atherosclerosis. Although many
      of their activities depend to various extents on changes in intracellular Ca(2+)
      concentration ([Ca(2+)](i)), mechanisms regulating [Ca(2+)](i) in these cells
      remain unclear. We aimed to explore the role of myosin light chain kinase (MLCK)
      in Ca(2+) signaling in freshly isolated human monocytes/macrophages. Large
      capacitative Ca(2+) entry (CCE) was observed under fura 2 fluoroscopy in human
      monocytes/macrophages treated with thapsigargin and cyclopiazonic acid. ML-9 and
      wortmannin, 2 structurally different inhibitors of MLCK, dose-dependently (1 to
      100 micromol/L) prevented CCE and completely did so at 100 micromol/L, whereas
      inhibitors of tyrosine kinase and protein kinase C had only partial effects.
      Western blotting showed that thapsigargin significantly caused myosin light chain
      phosphorylation, which was almost completely blocked by ML-9 (100 micromol/L) and
      wortmannin (100 micromol/L). ML-9 also dose-dependently (1 to 100 micromol/L)
      inhibited this phosphorylation, which was well correlated with its inhibition of
      CCE. Transfection with MLCK antisense completely prevented CCE in response to
      thapsigargin and cyclopiazonic acid, whereas MLCK sense had no effect. These data
      strongly indicate that MLCK regulates CCE in human monocytes/macrophages. The
      study suggests a possible involvement of MLCK in many Ca(2+)-dependent activities
      of monocytes/macrophages.

PMID- 11304466
TI  - Mast cell chymase induces apoptosis of vascular smooth muscle cells.
AB  - In human coronary atheromas, the numbers of degranulated mast cells and of
      apoptotic smooth muscle cells (SMCs) are increased. Accordingly, the possibility
      exists that mast cells participate in the regulation of SMC apoptosis in the
      lesions. Mast cells isolated from the serosal cavities of rats were stimulated to
      release their secretory granules. The neutral protease chymase, present in the
      exocytosed granules, was found to induce apoptosis when added to rat aortic SMCs
      in culture. The chymase-induced apoptosis of SMCs was detected by flow cytometry,
      microscopic analysis of cellular morphology, terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL), and electrophoretic
      demonstration of DNA laddering. Chymase induced SMC apoptosis in a dose- and time
      dependent manner, and its proteolytic activity was essential for the
      proapoptotic effect. In addition to rat chymase, recombinant human chymase was
      also found to induce apoptosis of human coronary artery SMCs in culture. These
      results suggest that mast cells may participate in the apoptotic regulation of
      SMCs in atherosclerotic lesions.

PMID- 11304467
TI  - Role of sex differences and effects of endothelial NO synthase deficiency in
      responses of carotid arteries to serotonin.
AB  - We examined the hypothesis that contraction of the carotid arteries to serotonin
      is normally inhibited by endothelial NO synthase (eNOS) and is enhanced in mice
      lacking the gene for eNOS. Because the influence of eNOS may vary with the sex of
      the mouse, we also tested whether responses to serotonin were dependent on sex.
      We studied carotid arteries in vitro from littermate control (eNOS(+/+)) mice,
      heterozygous (eNOS(+/-)) mice, and homozygous eNOS-deficient (eNOS(-/-)) mice
      (male and female). Contraction to serotonin was greater in male eNOS(+/+) mice
      than in female eNOS(+/+) mice. In male mice, contraction to serotonin increased
      by approximately 40% and 2.5-fold in male eNOS(+/-) and eNOS(-/-) mice,
      respectively. Contraction to serotonin was more than doubled in female eNOS(+/-)
      mice and increased >5-fold in arteries from eNOS(-/-) mice. In contrast, maximum
      vasoconstriction to U46619 was similar in male and female eNOS(+/+), eNOS(+/-),
      and eNOS(-/-) mice. Relaxation to acetylcholine was not different in male and
      female eNOS(+/+) or eNOS(+/-) mice but was absent in eNOS(-/-) mice. These
      findings suggest that the contraction of carotid arteries to serotonin is
      influenced by the sex of the animal. eNOS deficiency in gene-targeted mice is
      associated with enhanced contraction to serotonin, particularly in female mice,
      providing direct evidence that eNOS is a major determinant of vascular effects of
      serotonin. The results with eNOS(+/-) mice suggest a "gene-dosing" effect for
      vascular responses to serotonin.

PMID- 11304468
TI  - Nitric oxide differentially regulates induction of type II nitric oxide synthase
      in rat vascular smooth muscle cells versus macrophages.
AB  - We studied effects of nitric oxide (NO) released by different NO donors on
      induction of inducible NO synthase (iNOS) in rat aortic smooth muscle cells
      (RASMC) and rat macrophage cell line NR8383. iNOS protein expression induced by a
      CM (interleukin-1beta 250 U/mL, interferon-gamma 150 U/mL, and tumor necrosis
      factor-alpha 150 U/mL) was not affected by the NO donor SNAP (0.2 to 1 mmol/L) in
      RASMC at 24 hours of incubation but was dose-dependently decreased by SNAP in
      macrophages (maximal 60% inhibition). A fully functional -3.2-kb rat iNOS
      promoter was transfected into RASMC and macrophages. The CM-induced promoter
      activity in transfected macrophages was inhibited by SNAP (maximal 67%
      inhibition), but this inhibitory effect by SNAP was not observed in transfected
      RASMC. Electrophoretic mobility-shift assays demonstrated that nuclear factor
      kappaB (NF-kappaB) binding patterns were different in 2 cell types and that the
      ratio of p50:p65 subunits was significantly lower in macrophages than in RASMC.
      Furthermore, NF-kappaB activity was not affected by SNAP in RASMC but was reduced
      by SNAP in macrophages. Another putative NO donor, NOR3 (1 mmol/L), completely
      inhibited iNOS induction by CM in RASMC, but this was accompanied by severe
      cytotoxicity, which resulted in cell death. Similar concentrations of SNAP did
      not exhibit cytotoxicity in RASMC, whereas macrophages demonstrated 88% viability
      compared with cells without SNAP. NO synthase inhibitor N(g)-monomethyl-L
      arginine significantly inhibited CM-induced nitrite production in both cell types
      and stimulated iNOS protein expression in macrophages but did not affect iNOS
      expression in RASMC. These data strongly suggest that NO may affect
      transcriptional regulation of iNOS differently in RASMC versus macrophages,
      possibly by means of regulation of NF-kappaB activation.

PMID- 11304469
TI  - Expression of angiopoietin-1 in human glioblastomas regulates tumor-induced
      angiogenesis: in vivo and in vitro studies.
AB  - To define a role for the angiopoietin/Tie2 system in astrocytoma angiogenesis, we
      examined the expression of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) in
      these tumors by immunohistochemistry and in situ hybridization. Furthermore, we
      studied in vitro the effects elicited by glioblastoma cell-secreted Ang1 or by
      recombinant Ang1 on functions of endothelial cells (ECs). Our observations of
      astrocytomas show that a stage-specific induction of angiopoietins occurs and is
      correlated with angiogenic phases of different intensity. Ang1 expression was
      found in a few astrocytes scattered in the tumor at all stages of astrocytoma
      progression. In blood vessels, Ang1 mRNA increased progressively in high-grade
      glioblastomas, in which the number of vessels was higher than in low-grade
      tumors. Ang2 was detected in tumor cells and in ECs in high-grade astrocytomas,
      whereas its expression was negligible in low-grade tumors. Coculture of
      glioblastoma cell lines producing Ang1 with endothelium demonstrated a key role
      of this ligand in the control of EC network organization. We found that
      recombinant Ang1 in vitro induces EC spreading and reorganization of the cell
      monolayer into cordlike structures. These results suggest that Ang1 directly acts
      on ECs by modulating cell-cell and cell-matrix associations and promoting the
      differentiation phase of angiogenesis.

PMID- 11304470
TI  - Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar
      to paraoxonase-1 protein but is not regulated by oxidized lipids.
AB  - Paraoxonase-1 (PON1) is a secreted protein associated primarily with high density
      lipoprotein (HDL) and participates in the prevention of low density lipoprotein
      (LDL) oxidation. Two other paraoxonase (PON) family members, namely, PON2 and
      PON3, have been identified. In this study, we report the cloning and
      characterization of the human PON3 gene from HepG2 cells. Tissue Northern
      analysis identifies an approximately 1.3-kb transcript for PON3 primarily in the
      liver. PON3-specific peptide antibodies detect an approximately 40-kDa protein
      associated with HDL and absent from LDL. Pretreatment of cultured human aortic
      endothelial cells with supernatants from HeLa Tet On cell lines overexpressing
      PON3 prevents the formation of mildly oxidized LDL and inactivates preformed
      mildly oxidized LDL. In contrast to PON1, PON3 is not active against the
      synthetic substrates paraoxon and phenylacetate. Furthermore, PON3 expression is
      not regulated in HepG2 cells by oxidized phospholipids and is not regulated in
      the livers of mice fed a high-fat atherogenic diet.

PMID- 11304471
TI  - Adenovirus-mediated transfer of dominant-negative rho-kinase induces a regression
      of coronary arteriosclerosis in pigs in vivo.
AB  - Small GTPase Rho and its target Rho-kinase/ROK/ROCK play an important role in
      various cellular functions, including smooth muscle contraction, actin
      cytoskeleton organization, and cell adhesion and migration, all of which may be
      involved in the pathogenesis of arteriosclerosis. Here, we show that adenovirus
      mediated transfer of dominant-negative Rho-kinase (DNRhoK) induces a marked
      regression of coronary constrictive remodeling and abolishes coronary vasospastic
      activity in vivo. Porcine coronary segments were chronically treated with
      interleukin-1beta, which resulted in the development of constrictive remodeling
      and vasospastic responses to serotonin, as previously reported. Adenovirus
      mediated transfer of DNRhoK, but not that of beta-galactosidase, into the
      interleukin-1beta-treated coronary segment caused a marked regression of the
      constrictive remodeling and abolished the vasospastic activity in 3 weeks.
      Western blot analysis showed that the phosphorylation of adducin and the
      ezrin/radixin/moesin family, the target proteins of Rho-kinase, were upregulated
      at the coronary lesions and were significantly suppressed by the transfer of
      DNRHOK: These results indicate that Rho-kinase is substantially involved in
      coronary constrictive remodeling and vasospastic responses, both of which can be
      reversed by the selective inhibition of the molecule in our porcine model in
      vivo.

PMID- 11304472
TI  - Microsatellite mutation of type II transforming growth factor-beta receptor is
      rare in atherosclerotic plaques.
AB  - A somatic mutation within a microsatellite polyA tract in the coding region of
      the type II transforming growth factor (TGF)-beta receptor gene was reported to
      occur in human atherosclerotic and restenotic lesions. This mutation occurs
      frequently in colorectal cancer with the replication error repair phenotype and
      results in loss of sensitivity to the growth inhibitory effects of TGF-beta in
      cells from the tumors. The mutation was proposed to account for the clonal
      expansion of vascular smooth muscle cells observed in atherosclerotic plaques,
      through loss of the growth inhibitory effect of TGF-beta. The frequency of the
      mutation and the extent of clonal expansion of the mutated cells have major
      implications for the mechanism of atherogenesis and therapeutic strategies. We
      analyzed a set of 22 coronary arterial and 9 aortic samples containing early to
      advanced atherosclerotic lesions for the mutation in the type II TGF-beta
      receptor polyA tract. Only 1 coronary arterial sample from an advanced lesion
      showed detectable amounts of the mutation, present at a low level (8% of the DNA
      sample). The data imply that the mutation occurs only at low frequency and is not
      a major mechanistic contributor to the development of atherosclerosis.

PMID- 11304473
TI  - Oxidized LDL regulates vascular endothelial growth factor expression in human
      macrophages and endothelial cells through activation of peroxisome proliferator
      activated receptor-gamma.
AB  - Vascular endothelial growth factor (VEGF) has been recognized as an angiogenic
      factor that induces endothelial proliferation and vascular permeability. Recent
      studies have also suggested that VEGF can promote macrophage migration, which is
      critical for atherosclerosis. We have reported that VEGF is remarkably expressed
      in activated macrophages, endothelial cells, and smooth muscle cells within human
      coronary atherosclerotic lesions, and we have proposed the significance of VEGF
      in the progression of atherosclerosis. To clarify the mechanism of VEGF
      expression in atherosclerotic lesions, we examined the regulation of VEGF
      expression by oxidized low density lipoprotein (Ox-LDL), which is abundant in
      atherosclerotic arterial walls. A recent report has revealed that peroxisome
      proliferator-activated receptor-gamma (PPARgamma) is expressed not only in
      adipocytes but also in monocytes/macrophages and has suggested that PPARgamma may
      have a role in the differentiation of monocytes/macrophages. Furthermore, 9- and
      13-hydroxy-(S)-10,12-octadecadienoic acid (9- and 13-HODE, respectively), the
      components of Ox-LDL, may be PPARgamma ligands. Therefore, we investigated the
      involvement of PPARgamma in the regulation of VEGF by Ox-LDL. PPARgamma
      expression was detected in human monocyte/macrophage cell lines, human acute
      monocytic leukemia (THP-1) cells, and human coronary artery endothelial cells
      (HCAECs). Ox-LDL (10 to 50 microg/mL) upregulated VEGF secretion from THP-1 dose
      dependently. VEGF mRNA expression in HCAECs was also upregulated by Ox-LDL. The
      mRNA expression of VEGF in THP-1 cells and HCAECs was also augmented by PPARgamma
      activators, troglitazone (TRO), and 15-deoxy-(12,14)-prostaglandin J(2) (PGJ2).
      In contrast, VEGF expression in another monocyte/macrophage cell line, human
      histiocytic lymphoma cells (U937), which lacks PPARgamma expression, was not
      augmented by TRO or PGJ2. We established the U937 cell line, which permanently
      expresses PPARgamma (U937T). TRO and Ox-LDL augmented VEGF expression in U937T.
      In addition, VEGF production by THP-1 cells was significantly increased by
      exposure to 9-HODE and 13-HODE. In conclusion, Ox-LDL upregulates VEGF expression
      in macrophages and endothelial cells, at least in part, through the activation of
      PPARgamma.

PMID- 11304474
TI  - Relationship of insulin sensitivity and ApoB levels to intra-abdominal fat in
      subjects with familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is one of the most common familial
      dyslipidemias associated with premature heart disease. Subjects with FCHL
      typically have elevated apolipoprotein B (apoB) levels, variable elevations in
      cholesterol and/or triglycerides, and a predominance of small, dense, low density
      lipoprotein particles. It is thought that insulin resistance is important in the
      expression of the combined hyperlipidemia phenotype. To further characterize the
      relationship between insulin resistance and increased apoB levels, 11 subjects
      from well-characterized FCHL families and normal control subjects matched for
      weight and/or age underwent measurement of intra-abdominal fat (IAF) and
      subcutaneous fat (SQF) by CT scan, insulin sensitivity (Si) by the frequently
      sampled intravenous glucose tolerance test, and lipoprotein levels. Body mass
      index and IAF were higher and Si was lower (more insulin resistant) in the FCHL
      group than in the age-matched group, but the values were similar in the FCHL
      group and the age- and weight-matched control group. When the relationship
      between body fat distribution and Si was tested with multiple linear regression,
      only IAF was significantly correlated with Si after the addition of SQF and body
      mass index as independent variables. For any level of insulin sensitivity or IAF,
      however, apoB levels remained higher in the FCHL subjects than in the control
      groups. In conclusion, in FCHL, visceral obesity is an important determinant of
      insulin resistance. Visceral obesity and insulin resistance, however, do not
      fully account for the elevated levels of apoB in this disorder, and this study
      provides physiological support for separate, but additive, genetic determinants
      in the etiology of the lipid phenotype.

PMID- 11304475
TI  - Decreased smooth muscle cell/extracellular matrix ratio of media of femoral
      artery in patients with atherosclerosis and hyperhomocysteinemia.
AB  - The aim of this study was to determine whether the morphology of the muscular
      femoral artery in patients with atherosclerosis and hyperhomocysteinemia differs
      from that of atherosclerotic vessels from patients with normal homocysteine
      levels. Whole-vessel biopsies of the superficial femoral artery were taken from
      patients with symptomatic atherosclerotic disease with and without
      hyperhomocysteinemia and from patients without atherosclerosis from traumatic
      amputations. The morphology of these specimens was studied qualitatively by light
      and electron microscopy and quantitatively by light microscopy in combination
      with a video overlay system. Atherosclerotic lesions in patients with
      hyperhomocysteinemia were morphologically similar to those in patients with
      normal homocysteine levels, except for a significantly decreased smooth muscle
      cell/extracellular matrix ratio of the media in hyperhomocysteinemic patients
      (P=0.02 versus normohomocysteinemic atherosclerotic group and P=0.001 versus
      group without a history of cardiovascular disease). Hyperhomocysteinemia is
      associated with a significant decrease of the smooth muscle cell/extracellular
      matrix ratio of the media of muscular femoral arteries without significant
      changes in medial thickness. Further investigations should concentrate on the
      cause of this newly discovered phenomenon and its impact on vascular compliance.

PMID- 11304476
TI  - Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of
      apolipoprotein E-deficient mice.
AB  - In epidemiological studies, an association between cardiovascular disease and
      Chlamydia pneumoniae (C pneumoniae) infection has been observed. Although C
      pneumoniae has been shown to be present in atherosclerotic lesions, a causal
      relationship between C pneumoniae infection and atherosclerosis has not been
      demonstrated. To study this question, we used 2 strains of apolipoprotein (apo) E
      deficient mice. Eight-week-old mice on an FVB background that were maintained on
      either a low- or a high-fat diet were infected 3 times at 1-week intervals with C
      pneumoniae, and atherosclerotic lesions were measured in the aortic root at 10
      weeks after the primary infection. In each of the diet groups, no difference in
      the extent of atherosclerosis could be observed between the C pneumoniae-infected
      and control animals. In further studies, 2 strains of apoE-deficient mice (FVB or
      C57BL/6J background) were infected 4 times at 3- to 4-week intervals, and the
      extent of atherosclerosis was analyzed 18 weeks later. The mice were kept on
      either a low- or a high-fat diet. The high-fat diet increased atherosclerosis,
      and a difference in atherosclerosis susceptibility between the mouse strains was
      observed. However, C pneumoniae infection did not influence lesion size in either
      mouse strain. On the other hand, C pneumoniae could not be demonstrated by
      polymerase chain reaction in any of the atherosclerotic lesions of the infected
      animals studied. A small decrease in serum cholesterol and triglyceride levels 3
      days after the primary infection occurred, but after that no differences in serum
      lipid levels compared with those in noninfected animals were evident. In the
      myocardium of C pneumoniae-infected mice, no inflammatory signs could be
      observed. We conclude that under the experimental conditions used, C pneumoniae
      infection does not accelerate atherogenic changes in the aortic root of apoE
      deficient mice.

PMID- 11304477
TI  - Dietary cosupplementation with vitamin E and coenzyme Q(10) inhibits
      atherosclerosis in apolipoprotein E gene knockout mice.
AB  - Intimal oxidation of LDL is considered an important early event in atherogenesis,
      and certain antioxidants are antiatherogenic. Dietary coenrichment with vitamin E
      (VitE) plus ubiquinone-10 (CoQ(10), which is reduced during intestinal uptake to
      the antioxidant ubiquinol-10, CoQ(10)H(2)) protects, whereas enrichment with VitE
      alone can increase oxidizability of LDL lipid against ex vivo oxidation. In the
      present study, we tested whether VitE plus CoQ(10) cosupplementation is more
      antiatherogenic than either antioxidant alone, by use of apolipoprotein E
      deficient (apoE-/-) mice fed a high-fat diet without (control) or with 0.2%
      (wt/wt) VitE, 0.5% CoQ(10), or 0.2% VitE plus 0.5% CoQ(10) (VitE+CoQ(10)) for 24
      weeks. None of the supplements affected plasma cholesterol concentrations,
      whereas in the VitE and CoQ(10) groups, plasma level of the respective supplement
      increased. Compared with control, plasma from CoQ(10) or VitE+CoQ(10) but not
      VitE-supplemented animals was more resistant to ex vivo lipid peroxidation
      induced by peroxyl radicals. VitE supplementation increased VitE levels in aorta,
      heart, brain, and skeletal muscle, whereas CoQ(10) supplementation increased
      CoQ(10) only in plasma and aorta and lowered tissue VITE: All treatments
      significantly lowered aortic cholesterol compared with control, but only
      VitE+CoQ(10) supplementation significantly decreased tissue lipid hydroperoxides
      when expressed per parent lipid. In contrast, none of the treatments affected
      aortic ratios of 7-ketocholesterol to cholesterol. Compared with controls,
      VitE+CoQ(10) supplementation decreased atherosclerosis at the aortic root and
      arch and descending thoracic aorta to an extent that increased with increasing
      distance from the aortic root. CoQ(10) significantly inhibited atherosclerosis at
      aortic root and arch, whereas VitE decreased disease at aortic root only. Thus,
      in apoE-/- mice, VitE+CoQ(10) supplements are more antiatherogenic than CoQ(10)
      or VitE supplements alone and disease inhibition is associated with a decrease in
      aortic lipid hydroperoxides but not 7-ketocholesterol.

PMID- 11304478
TI  - Measurement of copper-binding sites on low density lipoprotein.
AB  - Copper is often used to oxidize low density lipoprotein (LDL) in experiments in
      vitro and is a candidate for oxidizing LDL in atherosclerotic lesions. The
      binding of copper ions to LDL is usually thought to be a prerequisite for LDL
      oxidation by copper, although estimates of LDL copper binding vary widely. We
      have developed and validated an equilibrium dialysis assay in a MOPS-buffered
      system to measure copper binding to LDL and have found 38.6+/-0.7 (mean+/-SEM,
      n=25) copper binding sites on LDL. The binding was saturated at a copper
      concentration of 10 micromol/L at LDL concentrations of up to 1 mg protein/mL.
      Copper-binding capacity increased progressively and markedly when LDL was
      oxidized to increasing extents. Chemical modification of histidyl and lysyl
      residues on apolipoprotein B-100 reduced the number of binding sites by 56% and
      23%, respectively. As an example of the potential of this method to assess the
      effects of antioxidants on copper binding to LDL, we have shown that the
      flavonoids myricetin, quercetin, and catechin (but not epicatechin, kaempferol,
      or morin), at concentrations equimolar to the copper present (10 micromol/L),
      significantly decreased copper binding to LDL by 82%, 56%, and 20%, respectively.

PMID- 11304479
TI  - C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the
      Speedwell study: are inflammation and fibrin turnover linked in pathogenesis?
AB  - Plasma levels of C-reactive protein (CRP, a marker of the reactant plasma protein
      component of the inflammatory response) and of fibrin D-dimer (a marker of cross
      linked fibrin turnover) have each been associated in recent studies with the risk
      of future ischemic heart disease (IHD). Previous experimental studies have shown
      that fibrin degradation products, including D-dimer, have effects on inflammatory
      processes and acute-phase protein responses. In the Speedwell Prospective Study,
      we therefore measured CRP and D-dimer levels in stored plasma samples from 1690
      men aged 49 to 67 years who were followed-up for incident IHD for an average of
      75+/-4 months (mean+/-SD) and studied their associations with each other, with
      baseline and incident IHD, and with IHD risk factors. CRP and D-dimer levels were
      each associated with age, plasma fibrinogen, smoking habit, and baseline evidence
      of IHD. CRP was associated with D-dimer (r=0.21, P<0.00001). On univariate
      analyses, both CRP and D-dimer were associated with incident IHD. The incidence
      of IHD increased with CRP independently of the level of D-dimer (P=0.0002) and
      also increased with D-dimer independently of the level of CRP (P=0.048). In
      multivariate analyses, inclusion of D-dimer and conventional risk factors reduced
      the strength of the association between CRP and incident IHD; likewise, inclusion
      of CRP and conventional risk factors reduced the strength of the association
      between D-dimer and incident IHD. We conclude that although these respective
      markers of inflammation and fibrin turnover show modest association with each
      other in middle-aged men, they may have additive associations with risk of
      incident IHD. Further larger studies are required to test this hypothesis.

PMID- 11304480
TI  - Prospective study of fibrinolytic factors and incident coronary heart disease:
      the Atherosclerosis Risk in Communities (ARIC) Study.
AB  - The fibrinolytic system may play a role in the pathogenesis of coronary heart
      disease (CHD), but existing prospective studies have not consistently shown an
      independent association between fibrinolytic factors and CHD. None has reported
      an association between plasminogen and CHD incidence. In the prospective
      Atherosclerosis Risk in Communities (ARIC) Study of middle-aged adults, we
      examined the association of incident CHD with several fibrinolytic factors:
      tissue plasminogen activator antigen, plasminogen activator inhibitor-1,
      plasminogen, and fibrin fragment D-dimer as well as a marker of coagulation
      activation (prothrombin fragment F1.2). We measured these in stored baseline
      plasma samples of 326 subjects who developed CHD and, for comparison, a
      stratified random sample of the entire cohort (n=720). Tissue plasminogen
      activator and plasminogen activator inhibitor-1 antigen levels were associated
      positively with CHD incidence in analyses adjusted for age, race, and sex but
      were not associated with CHD after adjustment for other risk factors. Plasminogen
      and D-dimer levels were associated positively and independently with CHD
      incidence; the multivariable-adjusted relative risks (95% CIs) for the highest
      versus lowest quintiles were 2.20 (1.2 to 4.2) for plasminogen and 4.21 (1.9 to
      9.6) for D-dimer. F1.2 was not associated with CHD incidence. Our findings lend
      support for a link between fibrinolytic factors and CHD incidence. A positive
      association between plasminogen and CHD is seemingly opposite the direction
      expected but may reflect a compensatory response to impaired plasminogen
      activation in subjects prone to CHD.

PMID- 11304481
TI  - Platelet adhesion enhances the glycoprotein VI-dependent procoagulant response:
      Involvement of p38 MAP kinase and calpain.
AB  - In the final stages of activation, platelets express coagulation-promoting
      activity by 2 simultaneous processes: exposure of aminophospholipids, eg,
      phosphatidylserine (PS), at the platelet surface, and formation of membrane
      blebs, which may be shed as microvesicles. Contact with collagen triggers both
      processes via platelet glycoprotein VI (GPVI). Here, we studied the capacity of 2
      GPVI ligands, collagen-related peptide (CRP) and the snake venom protein
      convulxin (CVX), to elicit the procoagulant platelet response. In platelets in
      suspension, either ligand induced full aggregation and high Ca(2+) signals but
      little microvesiculation or PS exposure. However, most of the platelets adhering
      to immobilized CRP or CVX had exposed PS and formed membrane blebs after a
      prolonged increase in cytosolic [Ca(2+)](i). Platelets adhering to fibrinogen
      responded similarly but only when exposed to soluble CRP or CVX. By scanning
      electron microscopic analysis, the bleb-forming platelets were detected as either
      round, spongelike structures with associated microparticles or as arrays of
      vesicular cell fragments. The phosphorylation of p38 mitogen-activated protein
      kinase (MAPK) elicited by CRP and CVX was enhanced in fibrinogen-adherent
      platelets compared with that in platelets in suspension. The p38 inhibitor
      SB203580 and the calpain protease inhibitor calpeptin reduced only the
      procoagulant bleb formation, having no effect on PS exposure. Inhibition of p38
      also downregulated calpain activity. We conclude that the procoagulant response
      evoked by GPVI stimulation is potentiated by platelet adhesion. The sequential
      activation of p38 MAPK and calpain appears to regulate procoagulant membrane
      blebbing but not PS exposure.

PMID- 11304482
TI  - Procoagulant activity on platelets adhered to collagen or plasma clot.
AB  - In a new 2-stage assay of platelet procoagulant activity (PCA), we first
      subjected gel-filtered platelets to adhesion on collagen (as a model of primary
      hemostasis) or plasma clots (as a model of preformed thrombus) for 30 minutes,
      and then the adherent platelets were supplemented with pooled, reptilase-treated,
      diluted plasma. Defibrinated plasma provided coagulation factors for assembly on
      platelet membranes without uncontrolled binding of thrombin to fibrin(ogen).
      Platelet adhesion to both surfaces showed modest individual variation, which
      increased at platelet densities that allowed aggregation. However, adhesion
      induced PCA varied individually and surface-independently >3-fold, suggesting a
      uniform platelet procoagulant mechanism. Permanently adhered platelets showed
      markedly enhanced PCA when compared with the platelet pool in suspension, even
      after strong activation. The rate of thrombin generation induced by clot-adherent
      platelets was markedly faster than on collagen-adherent platelets during the
      initial phase of coagulation, whereas collagen-induced PCA proceeded slowly,
      strongly promoted by tissue thromboplastin. Therefore at 10 minutes, after
      adjustment for adhered platelets, collagen supported soluble thrombin formation
      as much as 5 times that of the thrombin-retaining clots. Activation of platelets
      by their firm adhesion was accompanied by formation of microparticles,
      representing about one third of the total soluble PCA. Collagen-adhered platelets
      provide soluble thrombin and microparticles, whereas the preformed clot serves to
      localize and accelerate hemostasis at the injury site, with the contribution of
      retained thrombin and microparticles.

PMID- 11304483
TI  - Stimulating G protein-coupled receptors: cure or cause for heart failure?

PMID- 11304484
TI  - Reactive oxygen species and death: oxidative DNA damage in atherosclerosis.

PMID- 11304485
TI  - Thrombin, thrombomodulin, and extracellular signal-regulated kinases regulating
      cellular proliferation.

PMID- 11304486
TI  - Enhanced angiotensin II activity in heart failure: reevaluation of the
      counterregulatory hypothesis of receptor subtypes.
AB  - There are strong data favoring the pathogenic role of angiotensin II type 1
      receptor (AT(1)) activation with subsequent promotion of myocyte growth and
      cardiac fibrosis in the development of cardiac hypertrophy and heart failure. An
      emerging hypothesis suggests that the activity of the angiotensin II type 2
      receptor (AT(2)) may counterregulate AT(1) receptor effects during cardiac
      development and during the evolution of cardiac hypertrophy and heart failure. In
      this review, we examine the potential role of AT(2) activity in the context of
      this hypothesis. In contrast to the counterregulatory hypothesis, studies in mice
      with an overabundance of, or a deficiency in, the AT(2) receptor do not suggest
      that AT(2) signaling is essential for cardiac development. Moreover, the proposed
      antigrowth effects of AT(2) receptor signaling in pathological cardiac
      hypertrophy could not be shown in two mice models both deficient in AT(2)
      receptors. The role of AT(2) receptor signaling in cardiac fibrosis is, however,
      still debatable because of conflicting data in the same two studies. In
      angiotensin II-evoked apoptosis in cardiomyocytes, the proposed proapoptotic role
      of AT(2) activity could not be confirmed. Furthermore, in the progression from
      the bench to bedside, the results of two large clinical trials in heart failure,
      namely ELITE II and Val-HeFT, can be explained without ascribing a major
      protective role to the unopposed activity of the AT(2) receptor in the failing
      myocardium. In this review, we conclude that the collective evidence does not
      strongly support a net beneficial effect of AT(2) stimulation in the diseased
      myocardium.

PMID- 11304487
TI  - Adenoviral delivery of a leukocyte-type 12 lipoxygenase ribozyme inhibits effects
      of glucose and platelet-derived growth factor in vascular endothelial and smooth
      muscle cells.
AB  - The lipoxygenase (LO) pathway has been implicated as an important mediator of
      chronic glucose and platelet-derived growth factor (PDGF)-induced effects in the
      vascular system. Endothelial cells treated with 12LO products or cultured in high
      glucose showed enhanced monocyte adhesion, an important step in atherogenesis. We
      have previously reported that PDGF increased HETE levels in porcine aortic smooth
      muscle cells. Although several pharmacological inhibitors to the LO pathway are
      available, most lack specificity and may harbor undesirable side effects.
      Therefore, we developed a recombinant adenovirus expressing a hammerhead ribozyme
      (AdRZ) targeted against the porcine leukocyte-type 12LO mRNA to investigate the
      involvement of LO in glucose- and PDGF-mediated effects in vascular cells.
      Infection of porcine aortic endothelial cells with AdRZ reduced the level of
      glucose-enhanced 12LO mRNA expression as determined by quantitative, real-time
      reverse transcriptase-polymerase chain reaction. Reverse-phase HPLC and RIA
      analysis also revealed a corresponding decrease in glucose-stimulated 12HETE
      production in both the cellular and supernatant fractions. In the ribozyme
      treated porcine aortic endothelial cells, there was marked inhibition of high
      glucose-stimulated monocyte adhesion. Infection with AdRZ also reduced PDGF
      induced porcine aortic smooth muscle cell migration by approximately 50%. These
      studies demonstrate the efficacy of recombinant adenovirus expressing 12LO
      ribozyme in studying the effects of 12LO in vascular wall cells. They document an
      important role for the 12LO pathway in regulating inflammatory changes in
      endothelial cells and smooth muscle cells.

PMID- 11304488
TI  - The carboxyl terminal domain regulates the unitary conductance and voltage
      dependence of connexin40 gap junction channels.
AB  - Chemical regulation of connexin (Cx) 40 and Cx43 follows a ball-and-chain model,
      in which the carboxyl terminal (CT) domain acts as a gating particle that binds
      to a receptor affiliated with the pore. Moreover, Cx40 channels can be closed by
      a heterodomain interaction with the CT domain of Cx43 and vice versa. Here, we
      report similar interactions in the establishment of the unitary conductance and
      voltage-dependent profile of Cx40 in N2A cells. Two mean unitary conductance
      values ("lower conductance" and "main") were detected in wild-type Cx40.
      Truncation of the CT domain at amino acid 248 (Cx40tr248) caused the
      disappearance of the lower-conductance state. Coexpression of Cx40tr248 with the
      CT fragment of either Cx40 (homodomain interactions) or Cx43 (heterodomain
      interactions) rescued the unitary conductance profile of Cx40. In the N2A cells,
      the time course of macroscopic junctional current relaxation was best described
      by a biexponential function in the wild-type Cx40 channels, but it was reduced to
      a single-exponential function after truncation. However, macroscopic junctional
      currents recorded in the oocyte expression system were not significantly
      different between the wild-type and mutant channels. Concatenation of the CT
      domain of Cx43 to amino acids 1 to 248 of Cx40 yielded a chimeric channel with
      unitary conductance and voltage-gating profile indistinguishable from that of
      wild-type Cx40. We conclude that residence of Cx40 channels in the lower
      conductance state involves a ball-and-chain type of interaction between the CT
      domain and the pore-forming region. This interaction can be either homologous
      (Cx40 truncation with Cx40CT) or heterologous (with the Cx43CT).

PMID- 11304489
TI  - Integrin-mediated mechanotransduction in vascular smooth muscle cells: frequency
      and force response characteristics.
AB  - Blood vessels are continuously exposed to mechanical forces that lead to adaptive
      remodeling and atherosclerosis. Although there have been many studies
      characterizing the responses of vascular cells to mechanical stimuli, the precise
      mechanical characteristics of the forces applied to cells to elicit these
      responses are not clear. We designed a magnetic exposure system capable of
      producing a defined normal force on ferromagnetic beads that are specifically
      bound to cultured cells coated with extracellular matrix proteins or integrin
      specific antibodies. Rat aortic smooth muscle cells were incubated with
      engineered fibronectin-coated ferromagnetic beads and then exposed to a magnetic
      field. With activation of extracellular signal-regulated mitogen-activated
      protein kinase 1/2 (ERK 1/2(MAPK)) used as a prototypical marker for cell
      responsiveness to mechanical forces, Western blot analysis demonstrated an
      increase in phosphorylated ERK 1/2(MAPK) expression reaching a maximal response
      of a 3.5-fold increase at a total force of approximately 2.5 pN per cell. The
      peak response occurred after 5 minutes of exposure and slowly decreased to
      baseline after 30 minutes. A cyclic, rather than static, force was required for
      this activation, and the frequency-response curve increased approximately 2-fold
      between 0.5 and 2.0 HZ: Vitronectin- and beta(3) antibody-coated beads showed a
      response nearly identical to those coated with engineered fibronectin, whereas
      forces applied to beads coated with alpha(2) and beta(1) antibodies did not
      significantly activate ERK 1/2(MAPK). Mechanical activation of the ERK 1/2(MAPK)
      system in rat aortic smooth muscle cells occurs through specific integrin
      receptors and requires a cyclic force with a magnitude estimated to be in the
      piconewton range.

PMID- 11304490
TI  - Thrombomodulin prolongs thrombin-induced extracellular signal-regulated kinase
      phosphorylation and nuclear retention in endothelial cells.
AB  - On endothelial cells, thrombin binds to thrombomodulin (TM), an integral membrane
      bound glycoprotein, and to protease-activated receptors (PARs). Thrombin binding
      to TM modulates endothelial cell and smooth muscle cell proliferation mediated
      through PAR1. We studied the phosphorylation and nuclear translocation of
      extracellular signal-regulated kinases (ERKs) 1 and 2 in human umbilical vein
      endothelial cells activated by thrombin. Thrombin and thrombin receptor
      activating peptide (TRAP)-induced DNA synthesis were significantly inhibited by
      PD98059, an inhibitor of ERK phosphorylation. Immunoblots of phosphorylated ERKs
      (pERKs) and immunocytochemical studies of pERK localization revealed differences
      in the signal generated by thrombin and TRAP. After a short activation (15
      minutes), the phosphorylation and the intracellular localization of pERKs were
      the same with the 2 agonists. After 4 hours, however, pERKs were visualized in
      the nuclei of thrombin-activated cells but barely detectable in TRAP-activated
      cells. Moreover, after 4 hours, the pERKs were visualized in the nuclei of cells
      stimulated by TRAP in the presence of a thrombin mutant that bound to TM, whereas
      they were around the nuclei in cells stimulated by thrombin in the presence of a
      monoclonal antibody preventing thrombin binding to TM. The results demonstrate
      that ERKs are involved in human umbilical vein endothelial cell DNA synthesis
      mediated by PAR agonists, that the duration of pERK nuclear retention is in
      inverse ratio to the mitogenic response, and that in addition to its role in the
      regulation of blood coagulation, TM acts as a thrombin receptor that modulates
      the duration of pERK nuclear retention and cell proliferation in response to
      thrombin.

PMID- 11304491
TI  - Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes:
      differential effects on contractility.
AB  - In heart failure, reduced cardiac contractility is accompanied by blunted cAMP
      responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related
      peptide and arginine vasopressin are released from the myocardium in response to
      increased wall stress but do not stimulate contractility or adenylyl cyclase at
      physiological concentrations. To bypass the defective beta-adrenergic signaling
      cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2)
      vasopressin receptors (rV(2)-Rs), which are normally not expressed in the
      myocardium and which are both strongly coupled to adenylyl cyclase, and
      recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in
      cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to
      increase contractility via the heterologous, recombinant receptors was compared.
      Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also
      coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult
      cardiomyocytes resulted in maximally increased basal contractility, which could
      not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs
      induced increased cAMP formation and phospholipase C activity. In contrast,
      healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal
      contractility. Their contractility and cAMP formation increased only at agonist
      exposure, which did not activate phospholipase C. In summary, we found that gene
      transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the
      transgene, as does that of beta(2)-ARS: In the absence of receptor agonists,
      rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins
      simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not
      constitutively active, retaining their property to be activated exclusively on
      agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to
      test the effects of cAMP-stimulating receptors in heart failure than that of PTH1
      Rs or beta(2)-ARS:

PMID- 11304492
TI  - Ischemic preconditioning upregulates vascular endothelial growth factor mRNA
      expression and neovascularization via nuclear translocation of protein kinase C
      epsilon in the rat ischemic myocardium.
AB  - Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C
      (PKC) activation, whereas myocardial ischemia enhances vascular endothelial
      growth factor (VEGF) mRNA expression. However, the IP effect or the involvement
      of PKC on the VEGF expression is unknown in myocardial infarction. We
      investigated whether IP enhances VEGF gene expression and angiogenesis through
      PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats
      were assigned into the following 3 groups: the sham group; the IP group, which
      underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP
      procedure); and the non-IP group. The latter 2 groups were subsequently subjected
      to left anterior descending coronary artery occlusion. To examine the involvement
      of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1
      mg/kg) was injected intravenously before the IP procedures. PKCepsilon was
      translocated to the nucleus after 10 minutes of ischemia after the IP procedure
      but was not translocated in the non-IP and the sham groups. VEGF mRNA expression
      3 hours after infarction was significantly higher in the IP group than in the non
      IP and the sham groups. Capillary density in the infarction was significantly
      higher, whereas the infarct size was smaller in the IP group than in the non-IP
      group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked
      all of the IP effects on the nuclear translocation of PKCepsilon, enhancement of
      VEGF mRNA expression and angiogenesis, and infarct size limitation. These results
      show that IP may enhance VEGF gene expression and angiogenesis through nuclear
      translocation of PKCepsilon in the infarcted myocardium.

PMID- 11304493
TI  - Multidimensional rhythm disturbances as a precursor of sustained ventricular
      tachyarrhythmias.
AB  - Cardiac cycle dynamics reflect underlying physiological changes that could
      predict imminent arrhythmias but are obscured by high complexity,
      nonstationarity, and large interindividual differences. To overcome these
      problems, we developed an adaptive technique, referred to as the modified
      Karhunen-Loeve transform (MKLT), that identifies an individual characteristic
      ("core") pattern of cardiac cycles and then tracks the changes in the pattern by
      projecting the signal onto characteristic eigenvectors. We hypothesized that
      disturbances in the core pattern, indicating progressive destabilization of
      cardiac rhythm, would predict the onset of spontaneous sustained ventricular
      tachyarrhythmias (VTAs) better than previously reported methods. We analyzed
      serial ambulatory ECGs recorded in 57 patients at the time of VTA and non-VTA 24
      hour periods. The disturbances in the pattern were found in 82% of the recordings
      before the onset of impending VTA, and their dimensionality, defined as the
      number of unstable orthogonal projections, increased gradually several hours
      before the onset. MKLT provided greater sensitivity and specificity (70% and 93%)
      compared with the best traditional method (68% and 67%, respectively). We present
      a theoretical analysis of MKLT and describe the effects of ectopy and slow
      changes in cardiac cycles on the disturbances in the pattern. We conclude that
      MKLT provides greater predictive accuracy than previously reported methods. The
      improvement is due to the use of individual patterns as a reference for tracking
      the changes. Because this approach is independent of the group reference values
      or the underlying clinical context, it should have substantial potential for
      predicting other forms of arrhythmic events in other populations.

PMID- 11304494
TI  - Adaptive mechanisms that preserve cardiac function in mice without myoglobin.
AB  - Mice lacking myoglobin survive to adulthood and meet the circulatory demands of
      exercise and pregnancy without cardiac decompensation. In the present study, we
      show that many myoglobin-deficient embryos die in utero at midgestation with
      signs of cardiac failure. Fetal mice that survive to gestational day 12.5,
      however, suffer no subsequent excess mortality. Survival in the absence of
      myoglobin is associated with increased vascularity and the induction of genes
      encoding the hypoxia-inducible transcription factors 1alpha and 2, stress
      proteins such as heat shock protein 27, and vascular endothelial growth factor.
      These adaptations are evident in late fetal life, persist into adulthood, and are
      sufficient to maintain normal myocardial oxygen consumption during stressed
      conditions. These data reveal that myoglobin is necessary to support cardiac
      function during development, but adaptive responses evoked in some animals can
      fully compensate for the defect in cellular oxygen transport resulting from the
      loss of myoglobin.

PMID- 11304495
TI  - Role of inducible nitric oxide synthase in the pulmonary vascular response to
      birth-related stimuli in the ovine fetus.
AB  - To determine whether type II nitric oxide synthase (NOS II) contributes to the NO
      mediated fall in pulmonary vascular resistance (PVR) at birth, we studied the
      effects of selective NOS II antagonists N-(3-aminomethyl) benzylacetamidine
      dihydrochloride (1400W) and aminoguanidine (AG) and a nonselective NOS
      antagonist, nitro-L-arginine (L-NA), during mechanical ventilation with low
      FIO(2) (<10%), high FIO(2) (100%), and inhaled NO (20 ppm) in 23 near-term fetal
      lambs. Intrapulmonary infusions of AG, 1400W, and L-NA increased basal PVR before
      delivery (P<0.05). In control animals, ventilation with low and high FIO(2)
      decreased PVR by 62% and 85%, respectively. Treatment with AG and 1400W
      attenuated the fall in PVR by 50% during ventilation with low and high FIO(2)
      (control versus treatment, P<0.05 for each intervention). L-NA treatment
      attenuated the fall in PVR during ventilation with low and high FIO(2) to a
      similar degree as the NOS II antagonists. To test the selectivity of the NOS II
      antagonists, we studied the effects of acetylcholine and inhaled NO in each study
      group. Acetylcholine-induced pulmonary vasodilation remained intact after
      treatment with selective NOS II antagonists but not after treatment with
      nonselective NOS blockade with L-NA. In contrast, the response to inhaled NO was
      similar between treatment groups. We conclude that selective NOS II inhibition is
      as effective as nonselective NOS blockade in attenuating pulmonary vasodilation
      at birth and speculate that NOS II activity contributes to NO-mediated pulmonary
      vasodilation at birth. We additionally speculate that stimulation of the airway
      epithelium by rhythmic distension and increased FIO(2) may activate NOS II
      release at birth.

PMID- 11304496
TI  - Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 is involved in gp130
      resistance in cardiovascular system in rat treated with cardiotrophin-1 in vivo.
AB  - CIS (cytokine-inducible SH2 protein), SOCS (suppressor of cytokine signaling), or
      SSI (signal transducers and activators of transcription [STAT]-induced STAT
      inhibitor) proteins are a family of cytokine-inducible negative regulators of
      cytokine signaling via Janus kinase (JAK)-STAT pathways. Given the evidence that
      the JAK-STAT pathway plays a critical role in the cardiovascular system, the
      primary objective of this study was to assess the effects of the CIS family on
      JAK-STAT signaling in the cardiovascular system in rats treated with
      cardiotrophin-1 (CT-1), an interleukin-6 family of cytokines. Intravenous
      injection of 20 microgram/kg body weight of CT-1 induced a transient, marked
      increase in STAT3 activation in various tissues, including heart and lung, and
      subsequent upregulation of 2 members of the CIS family, JAK-binding protein
      (JAB)/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3, in the same tissues. It was also
      observed that CIS3 was directly associated with JAK2 in vivo. Pretreatment with
      the same dose of CT-1 60 minutes before significantly attenuated the STAT3
      activation induced by a second injection of CT-1. We previously reported that
      intravenous injection of CT-1 results in the nitric oxide (NO)-dependent
      hypotension accompanied by the induction of inducible NO synthase mRNA. In rats
      pretreated with CT-1, the induction of inducible NO synthase mRNA or hypotension
      by subsequent CT-1 injection was not observed. Forced expression of JAB or CIS3,
      but not other CISs, directly blocked CT-1-induced STAT3 activation in 293 cells.
      These results suggest that JAB and CIS3 serve as endogenous inhibitors of CT-1
      mediated JAK-STAT signaling in the cardiovascular system in vivo.

PMID- 11304497
TI  - Oxidative DNA damage and repair in experimental atherosclerosis are reversed by
      dietary lipid lowering.
AB  - Increased oxidative stress is a major characteristic of hypercholesterolemia
      induced atherosclerosis. The oxidative environment is mainly created by the
      production of reactive oxygen species, which are assumed to mediate vascular
      tissue injury. Oxidative DNA damage resulting from free radical attack remains,
      however, a poorly examined field in atherosclerosis. Male New Zealand White
      rabbits were fed a cholesterol-rich diet (0.3%) for 24 weeks. The induced
      atherosclerotic plaques showed elevated levels of the DNA damage marker 7,8
      dihydro-8-oxoguanine (8-oxoG) as demonstrated by immunohistochemistry. 8-oxoG
      immunoreactivity was found predominantly in the superficial layer of the plaque
      containing numerous macrophage-derived foam cells but not in the media or in
      arteries of age-matched control animals. Alkaline single-cell gel electrophoresis
      revealed that the number of DNA strand breaks was significantly higher in the
      plaque as compared with control samples of normolipemic animals. These changes
      were associated with the upregulation of DNA repair enzymes (poly[ADP-ribose]
      polymerase-1, p53, phospho-p53 [phosphorylated at Ser392], and XRCC1 [x-ray
      repair cross-complementing 1]). DNA strand breaks normalized after 4 weeks of
      dietary lipid lowering. However, a significant reduction of 8-oxoG
      immunoreactivity was only observed after a prolonged period of lipid lowering (12
      to 24 weeks). Repair pathways started to decline progressively when cholesterol
      fed animals were placed on a normal diet. In conclusion, oxidative DNA damage and
      increased levels of DNA repair, both associated with diet-induced
      hypercholesterolemia, are strongly reduced during dietary lipid lowering. These
      findings may provide a better insight into the benefits of lipid-lowering therapy
      on plaque stabilization.

PMID- 11304498
TI  - Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in the
      cardiac Na(+) channel.
AB  - Variant 3 of the congenital long-QT syndrome (LQTS-3) is caused by mutations in
      the gene encoding the alpha subunit of the cardiac Na(+) channel. In the present
      study, we report a novel LQTS-3 mutation, E1295K (EK), and describe its
      functional consequences when expressed in HEK293 cells. The clinical phenotype of
      the proband indicated QT interval prolongation in the absence of T-wave
      morphological abnormalities and a steep QT/R-R relationship, consistent with an
      LQTS-3 lesion. However, biophysical analysis of mutant channels indicates that
      the EK mutation changes channel activity in a manner that is distinct from
      previously investigated LQTS-3 mutations. The EK mutation causes significant
      positive shifts in the half-maximal voltage (V(1/2)) of steady-state inactivation
      and activation (+5.2 and +3.4 mV, respectively). These gating changes shift the
      window of voltages over which Na(+) channels do not completely inactivate without
      altering the magnitude of these currents. The change in voltage dependence of
      window currents suggests that this alteration in the voltage dependence of Na(+)
      channel gating may cause marked changes in action potential duration because of
      the unique voltage-dependent rectifying properties of cardiac K(+) channels that
      underlie the plateau and terminal repolarization phases of the action potential.
      Na(+) channel window current is likely to have a greater effect on net membrane
      current at more positive potentials (EK channels) where total K(+) channel
      conductance is low than at more negative potentials (wild-type channels), where
      total K(+) channel conductance is high. These findings suggest a fundamentally
      distinct mechanism of arrhythmogenesis for congenital LQTS-3.

PMID- 11304499
TI  - Microtubule disruption by colchicine reversibly enhances calcium signaling in
      intact rat cardiac myocytes.
AB  - Using the whole-cell patch-clamp configuration in rat ventricular myocytes, we
      recently reported that microtubule disruption increases calcium current (I(Ca))
      and [Ca(2+)](i) transient and accelerates their kinetics by adenylyl cyclase
      activation. In the present report, we further analyzed the effects of microtubule
      disruption by 1 micromol/L colchicine on Ca(2+) signaling in cardiac myocytes
      with intact sarcolemma. In quiescent intact cells, it is possible to investigate
      ryanodine receptor (RyR) activity by analyzing the characteristics of spontaneous
      Ca(2+) sparks. Colchicine treatment decreased Ca(2+) spark amplitude (F/F(0):
      1.78+/-0.01, n=983, versus 1.64+/-0.01, n=1660, recorded in control versus
      colchicine-treated cells; P<0.0001) without modifying the sarcoplasmic reticulum
      Ca(2+) load and enhanced their time to peak (in ms: 6.85+/-0.09, n=1185, versus
      7.33+/-0.13, n=1647; P<0.0001). Microtubule disruption also induced the
      appearance of Ca(2+) sparks in doublets. These alterations may reflect RyR
      phosphorylation. To further investigate Ca(2+) signaling in cardiac myocytes with
      intact sarcolemma, we analyzed [Ca(2+)](i) transient evoked by field stimulation.
      Cells were loaded with the fluorescence Ca(2+) indicator, Fluo-3 cell permeant,
      and stimulated at 1 HZ: [Ca(2+)](i) transient amplitude was greater and its decay
      was accelerated in colchicine-treated, field-stimulated myocytes. This effect is
      reversible. When colchicine-treated myocytes were placed in a colchicine-free
      solution for 30 minutes, tubulin was repolymerized into microtubules, as shown by
      immunofluorescence, and the increase in [Ca(2+)](i) transient was reversed. In
      summary, we demonstrate that microtubule disruption by colchicine reversibly
      modulates Ca(2+) signaling in cardiac cells with intact sarcolemma.

PMID- 11304501
TI  - Theodore Cooper Lecture: Tissue angiotensin and pathobiology of vascular disease:
      a unifying hypothesis.
AB  - There is increasing evidence that direct pathobiological events in the vessel
      wall play an important role in vascular disease. An important mechanism involves
      the perturbation of the homeostatic balance between NO and reactive oxygen
      species. Increased reactive oxygen species can inactivate NO and produce
      peroxynitrite. Angiotensin II is a potent mediator of oxidative stress and
      stimulates the release of cytokines and the expression of leukocyte adhesion
      molecules that mediate vessel wall inflammation. Inflammatory cells release
      enzymes (including ACE) that generate angiotensin II. Thus, a local positive
      feedback mechanism could be established in the vessel wall for oxidative stress,
      inflammation, and endothelial dysfunction. Angiotensin II also acts as a direct
      growth factor for vascular smooth muscle cells and can stimulate the local
      production of metalloproteinases and plasminogen activator inhibitor. Taken
      together, angiotensin II can promote vasoconstriction, inflammation, thrombosis,
      and vascular remodeling. In this article, we propose a model that unifies the
      interrelationship among cardiovascular risk factors, angiotensin II, and the
      pathobiological mechanisms contributing to cardiovascular disease. This model may
      also explain the beneficial effects of ACE inhibitors on cardiovascular events
      beyond blood pressure reduction.

PMID- 11304502
TI  - Diabetes, hypertension, and cardiovascular disease: an update.
AB  - Cardiovascular diseases (CVDs) are the major causes of mortality in persons with
      diabetes, and many factors, including hypertension, contribute to this high
      prevalence of CVD. Hypertension is approximately twice as frequent in patients
      with diabetes compared with patients without the disease. Conversely, recent data
      suggest that hypertensive persons are more predisposed to the development of
      diabetes than are normotensive persons. Furthermore, up to 75% of CVD in diabetes
      may be attributable to hypertension, leading to recommendations for more
      aggressive treatment (ie, reducing blood pressure to <130/85 mm Hg) in persons
      with coexistent diabetes and hypertension. Other important risk factors for CVD
      in these patients include the following: obesity, atherosclerosis, dyslipidemia,
      microalbuminuria, endothelial dysfunction, platelet hyperaggregability,
      coagulation abnormalities, and "diabetic cardiomyopathy." The cardiomyopathy
      associated with diabetes is a unique myopathic state that appears to be
      independent of macrovascular/microvascular disease and contributes significantly
      to CVD morbidity and mortality in diabetic patients, especially those with
      coexistent hypertension. This update reviews the current knowledge regarding
      these risk factors and their treatment, with special emphasis on the
      cardiometabolic syndrome, hypertension, microalbuminuria, and diabetic
      cardiomyopathy. This update also examines the role of the renin-angiotensin
      system in the increased risk for CVD in diabetic patients and the impact of
      interrupting this system on the development of clinical diabetes as well as CVD.

PMID- 11304504
TI  - Aging and systolic hypertension: cluster patterns and problem-solving strategies
      to answer the genetic riddle.

PMID- 11304503
TI  - Hypothesis: pulse pressure and human longevity.
AB  - In exploration of the association between pulse pressure and longevity in humans,
      3 hypotheses are briefly discussed: the fetal origin hypothesis, antagonistic
      pleiotropy, and the telomere hypothesis of cellular aging. The implications of
      these hypotheses serve to draw a critical distinction between biologic age
      (aging) and chronological age and, thereby, offer an answer to a question that
      presently matters most in the field of hypertension: Why has it been so difficult
      to disentangle the genetic components of essential hypertension and to identify
      the variant genes responsible for elevated blood pressure in a large segment of
      the human population?

PMID- 11304505
TI  - Prognostic significance of serum creatinine and uric acid in older Chinese
      patients with isolated systolic hypertension.
AB  - We examined the relation of serum creatinine and uric acid to mortality and
      cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated
      systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We
      used Cox regression to correlate outcome with baseline serum creatinine and uric
      acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in
      the placebo-controlled Systolic Hypertension in China (Syst-China) TRIAL: Median
      follow-up was 3 years. In multiple Cox regression analysis with adjustment for
      gender, age, active treatment, and other significant covariates, serum creatinine
      was significantly associated with a worse prognosis. The relative hazard rates
      (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all
      cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003),
      1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a
      similar analysis, which also accounted for serum creatinine, serum uric acid was
      also significantly and independently associated with excess mortality of
      cardiovascular disease and stroke. The relative hazard rates associated with a 50
      micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for
      cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In
      conclusion, in older Chinese patients with isolated systolic hypertension, serum
      creatinine and serum uric acid were predictors of mortality.

PMID- 11304506
TI  - Vascular stiffness in women with systemic lupus erythematosus.
AB  - Large-vessel manifestations of systemic lupus erythematosus (SLE), a multisystem
      disease characterized by disturbances in the immune system, include higher than
      expected rates of hypertension and cardiovascular disease. Reductions in the
      elasticity of central arteries may act as a marker of early changes that
      predispose to the development of major vascular disease. This study evaluated
      risk factors associated with aortic stiffness measured by pulse wave velocity
      (PWV) in women with SLE. We expected SLE-specific factors, especially variables
      indicative of inflammation and active disease, to be associated with increasing
      PWV. The study population included 220 women currently enrolled in the Pittsburgh
      Lupus REGISTRY: All risk factor data were collected on the day of the ultrasound
      examinations. PWV waveforms were collected from the right carotid and femoral
      arteries by Doppler probes. The mean age of the women was 45.5+/-10.8 years, the
      median SLE disease duration approximated 9 years, and the mean PWV was 6.1+/-1.7
      m/s. Multiple regression models were stratified by menopausal status. Among
      postmenopausal women, PWV risk factors were primarily traditional factors and
      included age, systolic blood pressure, family history of vascular disease,
      carotid plaque, creatinine, obesity, glucose, white cell count, and cumulative
      SLE organ damage. Among premenopausal women, PWV risk factors consisted of a mix
      of SLE-related and traditional variables and included higher C3 levels, presence
      of ds-DNA antibodies, nonuse of hydroxychloroquine, lower leukocyte count, higher
      mean arterial pressure, and carotid plaque. SLE-specific variables appeared to be
      associated with increases in aortic PWV, indicating central artery stiffening.
      This was seen most clearly among premenopausal women. This finding may partially
      explain the higher rates of cardiovascular disease and hypertension observed in
      young women with SLE.

PMID- 11304507
TI  - Silent ST depression and cardiovascular end-organ damage in newly found, older
      hypertensives.
AB  - In hypertension, both reduced vascular supply and increased cardiac demand
      contribute to the development of (silent) myocardial ischemia. Our aim was to
      determine the prevalence of ST-segment depression and to analyze contributing
      factors in asymptomatic, previously untreated, older hypertensives. From a
      population survey, in 184 patients with mild hypertension (4 times systolic blood
      pressure >/=160 mm Hg and/or diastolic blood pressure >/=95 mm Hg), 60 to 75
      years of age, cardiovascular end-organ damage was measured. Episodes of ST
      segment depression were measured by 48-hour ambulatory Holter monitoring and were
      observed in 21 hypertensives (12%). They showed a significantly higher combined
      far-wall intima-media thickness of carotid and femoral arteries and more arterial
      plaques as measured by B-mode ultrasound compared with hypertensives without ST
      depression (0.00098+/-0.00021 versus 0.00088+/-0.00016 mm and 5.2+/-3.7 versus
      3.7+/-2.8 plaques, P<0.05, respectively), whereas left ventricular mass index was
      not different (111+/-18 versus 104+/-24 g/m(2); P=0.18, respectively). In
      hypertensives with transient ST-segment depression, a significant relation was
      found between left ventricular mass and ischemic burden (r=0.51, P=0.02).
      Approximately 1 of 8 unselected and previously untreated older hypertensives show
      asymptomatic ST-segment depression, suggestive of silent myocardial ischemia.
      These data suggest that vascular factors mainly determine the occurrence of
      ischemic ST-segment depression and cardiac factors determine the ischemic burden
      in older hypertensives.

PMID- 11304508
TI  - Therapeutic actions of a new synthetic vasoactive and natriuretic peptide,
      dendroaspis natriuretic peptide, in experimental severe congestive heart failure.
AB  - Dendroaspis natriuretic peptide (DNP), a recently discovered peptide, shares
      structural similarity to the other known natriuretic peptides, ANP, BNP, and CNP.
      Studies have reported that DNP is present in human and canine plasma and atrial
      myocardium and increased in plasma of humans with congestive heart failure (CHF).
      In addition, synthetic DNP is markedly natriuretic and diuretic and is a potent
      activator of cGMP in normal animals. To date, the ability of synthetic DNP to
      improve cardiorenal function in experimental CHF is unknown. Synthetic DNP was
      administered intravenously at 10 and 50 ng. kg(-1). min(-1) in dogs (n=7) with
      severe CHF induced by rapid ventricular pacing for 10 days at 245 bpm. In
      addition, we determined endogenous DNP in normal (n=4) and failing (n=4) canine
      atrial and ventricular myocardium. We report that administration of synthetic DNP
      in experimental severe CHF has beneficial cardiovascular, renal, and humoral
      properties. First, DNP in CHF decreased cardiac filling pressures, specifically
      right atrial pressure and pulmonary capillary wedge pressure. Second, DNP
      increased glomerular filtration rate in association with natriuresis and diuresis
      despite a reduction in mean arterial pressure. Third, DNP increased plasma and
      urinary cGMP and suppressed plasma renin activity. Fourth and finally, we report
      that DNP immunoreactivity is present in canine atrial and ventricular myocardium
      and increased in CHF. These studies report the acute intravenous actions of
      synthetic DNP in experimental severe CHF and suggest that on the basis of its
      beneficial properties, DNP may have potential as a new intravenous agent for the
      treatment of decompensated CHF.

PMID- 11304509
TI  - Endogenous cyclic AMP-adenosine pathway regulates cardiac fibroblast growth.
AB  - Our previous studies show that cardiac fibroblasts express the extracellular
      "cAMP-adenosine pathway," that is, the generation of adenosine from extracelluar
      cAMP. The goal of this study was to assess whether activation of the cAMP
      adenosine pathway by stimulation of endogenous cAMP synthesis regulates cardiac
      fibroblast growth. Cardiac fibroblasts in 3D cultures were used as the model
      system. Treatment of cardiac fibroblasts with forskolin, isoproterenol, or
      norepinephrine increased cAMP production and extracellular levels of adenosine,
      and these effects were prevented by inhibition of adenylyl cyclase (2',5'
      dideoxyadenosine). Treatment with forskolin, isoproterenol, or norepinephrine for
      24 hours inhibited DNA synthesis ((3)H-thymidine incorporation), and this effect
      was enhanced by combined inhibition of adenosine deaminase (erythro-9-[2-hydroxy
      3-nonyl] adenine) plus adenosine kinase (iodotubercidin). Inhibition of adenylyl
      cyclase or adenosine receptors (1,3-dipropyl-8-p-sulfophenylxanthine or KF17837)
      prevented the effects of forskolin, isoproterenol, and norepinephrine on DNA
      synthesis. Forskolin also inhibited protein synthesis ((3)H-leucine
      incorporation) and cell proliferation, and these effects were blocked by
      adenosine receptor antagonism. Treatment of cardiac fibroblasts with
      norepinephrine for >48 hours but not <48 hours increased DNA synthesis, protein
      synthesis, and cell number. However, blockade of adenylyl cyclase or antagonism
      of adenosine receptors caused norepinephrine to induce proliferation in <48
      hours. Our findings indicate that the endogenous cAMP-adenosine pathway regulates
      cardiac fibroblast growth.

PMID- 11304510
TI  - Fenestrations of the carotid internal elastic lamina and structural adaptation in
      stroke-prone spontaneously hypertensive rats.
AB  - Our aim was to determine the structural factors that determine the mechanical
      adaptation of the carotid arterial wall in stroke-prone hypertensive rats
      (SHRSP). Distensibility-pressure and elastic modulus-stress curves assessed by in
      vivo echo-tracking measurements indicated a reduction in arterial stiffness in 13
      week-old SHRSP compared with Wistar-Kyoto rats (WKY). Elastin and collagen
      contents determined biochemically were not different between SHRSP and WKY.
      Confocal microscopy showed that the mean area of fenestrations and fraction of
      area occupied by fenestrations of the internal elastic lamina (IEL) were smaller
      in SHRSP than in WKY, which indicated a reduction in stress-concentration effects
      within the IEL. Immunohistologic staining of EIIIA fibronectin isoform and total
      fibronectin (also as determined by Western blot) was greater in SHRSP, which
      suggested increased cell-matrix interactions. We suggest that these structural
      modifications of the vascular wall play a synergistic role in the mechanical
      adaptation to a high level of stress in SHRSP.

PMID- 11304511
TI  - Vasopeptidase inhibition exhibits endothelial protection in salt-induced
      hypertension.
AB  - Omapatrilat represents a new class of drugs capable of inhibiting both ACE and
      neutral endopeptidase 24.11, the so-called vasopeptidase inhibitors. It therefore
      contributes to neurohumoral modulation, which might improve endothelial function
      in cardiovascular diseases. This study investigated the effect of omapatrilat in
      comparison to the ACE inhibitor captopril on systolic blood pressure and
      endothelial function in salt-induced hypertension. Dahl salt-sensitive rats
      (n=6/group) on standard or salt-enriched (4% NaCl) chow were treated for 8 weeks
      with either omapatrilat (36+/-4 mg/kg per day), captopril (94+/-2 mg/kg per day),
      or placebo. Aortic rings were then isolated and suspended in organ chambers for
      isometric tension recording. Systolic blood pressure of salt-fed, placebo-treated
      animals increased to 196+/-6 mm Hg, which was prevented by omapatrilat (162+/-5
      mm Hg, P<0.05) and captopril (164+/-7 mm Hg, P<0.05) to a comparable degree. In
      control rats, acetylcholine (10(-10) to 10(-5) mol/L) induced endothelium
      dependent relaxation (97+/-4%), which was reduced by high-salt diet to 30+/-5%
      (P<0.005; n=6). Omapatrilat improved relaxation to a greater extent (86+/-5%)
      than did captopril (57+/-6%; P<0.05). eNOS protein expression and aortic
      nitrite/nitrate content were reduced in hypertensive rats and improved by both
      omapatrilat and captopril. Aortic endothelin-1 levels were increased in salt-fed
      animals and unaffected by omapatrilat or captopril. These data suggest that
      despite comparable blood pressure, omapatrilat is superior to captopril in
      improving endothelium-dependent relaxation in salt-sensitive hypertension.

PMID- 11304512
TI  - Sodium intake influences hemodynamic and neural responses to angiotensin receptor
      blockade in rostral ventrolateral medulla.
AB  - To determine the effects of physiological alterations in endogenous angiotensin
      II activity on basal renal sympathetic nerve activity (RSNA) and its arterial
      baroreflex regulation, angiotensin II type 1 receptor antagonists were
      microinjected into the rostral ventrolateral medulla of anesthetized rats
      consuming a low, normal, or high sodium diet that were instrumented for
      simultaneous measurement of arterial pressure and RSNA. Plasma renin activity was
      increased in rats fed a low sodium diet and decreased in those fed a high sodium
      diet. Losartan (50, 100, and 200 pmol) decreased heart rate and RSNA (but not
      mean arterial pressure) dose-dependently; the responses were significantly
      greater in rats fed a low sodium diet than in those fed a high sodium diet.
      Candesartan (1, 2, and 10 pmol) decreased mean arterial pressure, heart rate, and
      RSNA dose-dependently; the responses were significantly greater in rats fed a low
      sodium diet than in those fed a normal or high sodium diet. [D-Ala(7)]Angiotensin
      (1-7) (100, 200, and 1000 pmol) did not affect mean arterial pressure, heart
      rate, or RSNA in rats fed either a low or a high sodium diet. In rats fed a low
      sodium diet, candesartan reset the arterial baroreflex control of RSNA to a lower
      level of arterial pressure, and in rats with congestive heart failure,
      candesartan increased the arterial baroreflex gain of RSNA. Physiological
      alterations in the endogenous activity of the renin-angiotensin system influence
      the bradycardic, vasodepressor, and renal sympathoinhibitory responses to rostral
      ventrolateral medulla injection of antagonists to angiotensin II type 1 receptors
      but not to angiotensin-(1-7) receptors.

PMID- 11304513
TI  - Lacidipine prevents endothelial dysfunction in salt-loaded stroke-prone
      hypertensive rats.
AB  - Endothelium-dependent vasorelaxation is defective in hypertensive rats,
      especially in conduit arteries. In the stroke-prone spontaneously hypertensive
      rat, impaired endothelium-dependent vasorelaxation appears to contribute to the
      pathogenesis of stroke independent of blood pressure. Because treatment with
      lacidipine, a long-acting calcium channel blocker, protects against stroke and
      cardiovascular remodeling in this model, we investigated the effect of this
      treatment on endothelium-dependent vasorelaxation in the aorta. Stroke-prone rats
      were exposed to a salt-rich diet (1% NaCl in drinking water) with or without
      lacidipine (1 mg. kg(-1). d(-1)) for 6 weeks. A high-sodium diet (1) increased
      systolic blood pressure, aortic weight, and wall thickness and plasma renin
      activity (P<0.05); (2) markedly reduced nitric oxide (NO)-mediated, endothelium
      dependent relaxation of aortic rings to acetylcholine and the sensitivity to the
      relaxing effect of S-nitroso-N-acetylpenicillamine, an NO donor (P<0.001); and
      (3) induced an elevation of preproendothelin-1 mRNA levels in aortic tissue
      (P<0.01) without affecting endothelial NO synthase mRNA levels. Lacidipine
      treatment prevented the salt-dependent functional and structural alterations of
      the aorta, including the overexpression of the preproendothelin-1 gene, and
      increased endothelial NO synthase mRNA levels in aortic tissue (P<0.01). In
      conclusion, lacidipine protects stroke-prone hypertensive rats against the
      impairment of endothelium-dependent vasorelaxation evoked by a salt-rich diet,
      and this effect may contribute to its beneficial effect against end-organ damage
      and stroke.

PMID- 11304514
TI  - Abnormal platelet function and calcium handling in Dahl salt-hypertensive rats.
AB  - The effect of dietary salt on platelet function and Ca(2+) homeostasis was
      studied in Dahl (DS) rats, a genetic model of salt-sensitive hypertension. DS
      rats were fed a high-salt (DSHS) or a low-salt diet (DSLS) for up to 4 weeks, and
      the effects of salt loading on systolic blood pressure, platelet P-selectin
      expression, and platelet Ca(2+) homeostasis were measured. The high-salt diet
      increased blood pressure and markedly increased the amount of ionomycin (IM)
      releasable Ca(2+) in platelet intracellular stores (Ca(2+)/IM). The alteration in
      Ca(2+) stores was not prevented when the hypertension was prevented by treatment
      with hydralazine and reserpine. The Ca(2+) store filling during platelet exposure
      to 1 mmol/L Ca(2+) for 5 minutes and the rate of sarcoplasmic/endoplasmic Ca(2+)
      ATPase-dependent Ca(45) uptake were higher in DSHS compared with that in DSLS.
      There was a decrease in thrombin-induced Ca(2+) influx in platelets from DSHS;
      consistent with this, agonist-induced P-selectin expression was decreased. In
      DSLS, nitric oxide accelerated reloading of platelet Ca(2+) stores after their
      emptying by thrombin but failed to do so in DSHS. These results indicate that in
      DS rats, a high-salt diet increases sarcoplasmic/endoplasmic Ca(2+) ATPase
      activity and the Ca(2+)/IM but decreases the reuptake of Ca(2+) caused by nitric
      oxide. Decreases in Ca(2+) influx and platelet P-selectin expression might be
      explained by changes in intracellular Ca(2+) stores in DSHS rats, which
      apparently is a heritable response to a high-salt diet.

PMID- 11304515
TI  - Angiotensin-(1-7) does not affect vasodilator or TPA responses to bradykinin in
      human forearm.
AB  - Studies in isolated vessels and rat models of hypertension suggest that
      angiotensin (Ang)-(1-7) potentiates the vasodilator effect of bradykinin,
      possibly through ACE inhibition. We therefore tested the hypothesis that Ang-(1
      7) potentiates the vasodilator or tissue plasminogen activator (TPA) response to
      bradykinin in the human forearm vasculature. Graded doses of Ang-(1-7) (10, 100,
      and 300 pmol/min), bradykinin (47, 94, and 189 pmol/min), and Ang I (1, 10, and
      30 pmol/min) were administered through the brachial artery to 8 normotensive
      subjects in random order. Thirty minutes after initiation of a constant infusion
      of Ang-(1-7) (100 pmol/min), bradykinin and Ang I infusions were repeated. There
      were no systemic hemodynamic effects of the agonists. Bradykinin significantly
      increased forearm blood flow (P<0.001, from 3.8+/-0.5 to 13.9+/-3.1 mL/min per
      100 mL at 189 pmol/min) and net TPA release (P=0.007, from 1.1+/-1.0 to 23.6+/
      6.2 ng/min per 100 mL at 189 pmol/min), whereas Ang I caused vasoconstriction
      (P=0.003, from 3.3+/-0.4 to 2.5+/-0.3 mL/min per 100 mL at 30-pmol/min dose).
      There was no effect of Ang-(1-7) on either forearm blood flow (P=0.62, 3.3+/-0.4
      to 3.5+/-0.4 mL/min per 100 mL at 300 pmol/min) or TPA release (P=0.52, from
      0.7+/-0.8 to 1.0+/-0.7 ng/min/100 mL at 300 pmol/min). Moreover, there was no
      effect of 100 pmol/min Ang-(1-7) on the vasodilator [P=0.46 for Ang-(1-7) effect]
      or TPA [P=0.82 for Ang-(1-7) effect] response to bradykinin or the
      vasoconstrictor response to Ang I [P=0.62 for Ang-(1-7) effect]. These data do
      not support a role of Ang-(1-7), given at supraphysiological doses, in the
      regulation of human peripheral vascular resistance or fibrinolysis.

PMID- 11304516
TI  - Angiotensin-(1-7) downregulates the angiotensin II type 1 receptor in vascular
      smooth muscle cells.
AB  - Angiotensin (Ang)-(1-7) is a biologically active peptide of the renin-angiotensin
      system that has both vasodilatory and antiproliferative activities that are
      opposite the constrictive and proliferative effects of angiotensin II (Ang II).
      We studied the actions of Ang-(1-7) on the Ang II type 1 (AT(1)) receptor in
      cultured rat aortic vascular smooth muscle cells to determine whether the effects
      of Ang-(1-7) are due to its regulation of the AT(1) receptor. Ang-(1-7) competed
      poorly for [(125)I]Ang II binding to the AT(1) receptor on vascular smooth muscle
      cells, with an IC(50) of 2.0 micromol/L compared with 1.9 nmol/L for Ang II. The
      pretreatment of vascular smooth muscle cells with Ang-(1-7) followed by treatment
      with acidic glycine to remove surface-bound peptide resulted in a significant
      decrease in [(125)I]Ang II binding; however, reduced Ang II binding was observed
      only at micromolar concentrations of Ang-(1-7). Scatchard analysis of vascular
      smooth muscle cells pretreated with 1 micromol/L Ang-(1-7) showed that the
      reduction in Ang II binding resulted from a loss of the total number of binding
      sites [B(max) 437.7+/-261.5 fmol/mg protein in Ang-(1-7)-pretreated cells
      compared with 607.5+/-301.2 fmol/mg protein in untreated cells, n=5, P<0.05] with
      no significant effect on the affinity of Ang II for the AT(1) receptor.
      Pretreatment with the AT(1) receptor antagonist L-158,809 blocked the reduction
      in [(125)I]Ang II binding by Ang-(1-7) or Ang II. Pretreatment of vascular smooth
      muscle cells with increasing concentrations of Ang-(1-7) reduced Ang II
      stimulated phospholipase C activity; however, the decrease was significant
      (81.2+/-6.4%, P<0.01, n=5) only at 1 micromol/L Ang-(1-7). These results
      demonstrate that pharmacological concentrations of Ang-(1-7) in the micromolar
      range cause a modest downregulation of the AT(1) receptor on vascular cells and a
      reduction in Ang II-stimulated phospholipase C activity. Because the
      antiproliferative and vasodilatory effects of Ang-(1-7) are observed at nanomolar
      concentrations of the heptapeptide, these responses to Ang-(1-7) cannot be
      explained by competition of Ang-(1-7) at the AT(1) receptor or Ang-(1-7)-mediated
      downregulation of the vascular AT(1) receptor.

PMID- 11304517
TI  - Y-chromosome transfer induces changes in blood pressure and blood lipids in SHR.
AB  - Previous studies with chromosome-Y consomic strains of spontaneously hypertensive
      rats (SHR) and Wistar-Kyoto rats suggest that a quantitative trait locus for
      blood pressure regulation exists on chromosome Y. To test this hypothesis in the
      SHR-Brown Norway (BN) model and to study the effects of chromosome Y on lipid and
      carbohydrate metabolism, we produced a new consomic strain of SHR carrying the Y
      chromosome transferred from the BN rat. We found that replacing the SHR Y
      chromosome with the BN Y chromosome resulted in significant decreases in systolic
      and diastolic blood pressures in the SHR.BN-Y consomic strain (P<0.05). To elicit
      possible dietary-induced variation in lipid and glucose metabolism between the
      SHR progenitor and chromosome-Y consomic strains, we fed rats a high-fructose
      diet for 15 days in addition to the normal diet. On the high-fructose diet, the
      SHR.BN-Y consomic rats exhibited significantly increased levels of serum
      triglycerides and decreased levels of serum HDL cholesterol versus the SHR
      progenitor rats. Glucose tolerance and insulin/glucose ratios, however, were
      similar in both strains on both normal and high-fructose diets. These findings
      provide direct evidence that a gene or genes on chromosome Y contribute to the
      pathogenesis of spontaneous hypertension in the SHR-BN model. These results also
      indicate that transfer of the Y chromosome from the BN rat onto the SHR
      background exacerbates dietary-induced dyslipidemia in SHR. Thus, genetic
      variation in genes on the Y chromosome may contribute to variation in blood
      pressure and lipid levels and may influence the risk for cardiovascular disease.

PMID- 11304518
TI  - Dynamic analysis of renal nerve activity responses to baroreceptor denervation in
      hypertensive rats.
AB  - Sinoaortic and cardiac baroreflexes exert important control over renal
      sympathetic nerve activity. Alterations in these reflex mechanisms contribute to
      renal sympathoexcitation in hypertension. Nonlinear dynamic analysis was used to
      examine the chaotic behavior of renal sympathetic nerve activity in normotensive
      Sprague-Dawley and Wistar-Kyoto rats and spontaneously hypertensive rats before
      and after complete baroreceptor denervation (sinoaortic and cardiac baroreceptor
      denervation). The peak interval sequence of synchronized renal sympathetic nerve
      discharge was extracted and used for analysis. In all rat strains, this yielded
      systems whose correlation dimensions converged to similar low values over the
      embedding dimension range of 10 to 15 and whose greatest Lyapunov exponents were
      positive. In Sprague-Dawley and Wistar-Kyoto rats, compete baroreceptor
      denervation was associated with decreases in the correlation dimensions (Sprague
      DAWLEY: 2.42+/-0.04 to 2.16+/-0.04; Wistar-KYOTO: 2.44+/-0.04 to 2.34+/-0.04) and
      in the greatest Lyapunov exponents (Sprague-DAWLEY: 0.199+/-0.004 to 0.130+/
      0.015; Wistar-KYOTO: 0.196+/-0.002 to 0.136+/-0.010). Spontaneously hypertensive
      rats had a similar correlation dimension, which was unaffected by complete
      baroreceptor denervation (2.42+/-0.02 versus 2.42+/-0.03), and a lower value for
      the greatest Lyapunov exponent, which decreased to a lesser extent after complete
      baroreceptor denervation (0.183+/-0.006 versus 0.158+/-0.006). These results
      indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal
      sympathetic nerve activity is associated with a greater decrease in the chaotic
      behavior of renal sympathetic nerve activity in normotensive compared with
      hypertensive rats. This suggests that the central neural mechanisms that regulate
      renal sympathetic nerve activity in response to alterations in cardiovascular
      reflex inputs are different in spontaneously hypertensive rats from those in
      Sprague-Dawley and Wistar-Kyoto rats.

PMID- 11304519
TI  - Decreased renal expression of nitric oxide synthase isoforms in
      adrenocorticotropin-induced and corticosterone-induced hypertension.
AB  - Administration of adrenocorticotropic hormone (ACTH) leads to the development of
      hypertension. Because glucocorticoids can affect the nitric oxide system at
      several sites, the present study tested the hypothesis that nitric oxide synthase
      (NOS) expression may be altered in ACTH-induced and corticosterone-induced
      hypertension in the rat. This was addressed by measuring Nos1, Nos2, and Nos3
      mRNA in the kidney, adrenal gland, heart, and hypothalamus of 16 ACTH-treated and
      16 vehicle-treated rats as well as in 10 corticosterone-treated and 10 control
      rats. In addition, in situ hybridization and immunohistochemistry were used to
      confirm changes by detection of Nos in RNA and NOS protein in tissues. Systolic
      blood pressure of ACTH and corticosterone rats was elevated (165+/-6 and 162+/-11
      mm Hg; P<0.001 versus control). Each Nos isoform mRNA was measured by reverse
      transcriptase-polymerase chain reaction technique. In ACTH rats, mRNA for Nos2
      was reduced in renal cortex by 58+/-5% and in medulla by 68+/-7%; for Nos3, mRNA
      reductions of 59+/-6% and 51+/-11% were seen (P<0.001 after Hochberg correction
      for multiple comparisons). In corticosterone rats, Nos2 mRNA decreased in cortex
      by 68+/-5% and in medulla by 62+/-6%; Nos3 mRNA by 50+/-8% in cortex, and Nos1 by
      29+/-7% in medulla (all P<0.001 after Hochberg correction). Reductions seen in
      kidney were supported by in situ hybridization and immunohistochemistry. Apart
      from a 62+/-2% decrease in Nos2 mRNA in adrenal of ACTH rats (corrected P<0.05),
      no significant changes were seen in the other nonrenal tissues for any isoform.
      In conclusion, we have shown for the first time that the physiological components
      of glucocorticoid action (ACTH and corticosterone) when given chronically in vivo
      reduce Nos2 and Nos3 expression in the kidney. Such changes are consistent with a
      role in hypertension for ACTH and corticosterone.

PMID- 11304520
TI  - Activation of NF-kappaB in tubular epithelial cells of rats with intense
      proteinuria: role of angiotensin II and endothelin-1.
AB  - The mechanisms by which persistent proteinuria induces interstitial inflammation
      and fibrosis are not well known, although nuclear factor-kappaB (NF-kappaB),
      which regulates the transcription of many genes involved in renal injury, could
      be implicated. In rats with intense proteinuria, we studied the renal activation
      of NF-kappaB as well as the potential involvement of the vasoactive hormones
      angiotensin II (Ang II) and endothelin-1 (ET-1). Uninephrectomized Wistar-Kyoto
      rats receiving 1 g/d of BSA had proteinuria but no renal morphological lesions at
      day 1. By contrast, tubular atrophy and/or dilation and mononuclear cell
      infiltration were observed after 8 or 28 days of BSA administration, coinciding
      with maximal proteinuria. In relation to control uninephrectomized rats, the
      renal cortex of nephritic rats showed an increment in the activation of NF-kappaB
      at all time periods studied. By in situ Southwestern histochemistry, NF-kappaB
      activity was mainly localized in proximal tubules, interstitial mononuclear
      cells, and, to a lesser extent, the glomeruli. The administration of the ACE
      inhibitor quinapril plus the ET(A)/ET(B) receptor antagonist bosentan during 28
      days to BSA-overloaded animals diminished proteinuria, renal lesions, and NF
      kappaB activity more markedly than single drugs. Cultured tubular epithelial
      cells exposed to BSA revealed an intense NF-kappaB activation in a time- and dose
      dependent manner. Incubation of cells with receptor antagonists of Ang II (AT(1):
      losartan and AT(2): PD-123,319) or ET-1 (ET(A): BQ123 and ET(B): IRL1038)
      inhibited significantly the BSA-induced NF-kappaB activity (90%, 75%, 90%, and
      60% of inhibition versus basal, respectively). Our results show that overload
      proteinuria causes NF-kappaB activation in tubular epithelial cells both in vivo
      and in vitro. The vasoactive peptides Ang II and ET-1 appear to be implicated in
      this effect. The results reveal a novel mechanism of perpetuation of renal damage
      induced by persistent proteinuria.

PMID- 11304521
TI  - C-type natriuretic peptide-induced vasodilation is dependent on hyperpolarization
      in human forearm resistance vessels.
AB  - Animal studies have demonstrated that CNP causes endothelium-independent
      vasodilation, which is limited by neutral endopeptidase (NEP) activity. However,
      the vasodilating mechanism of CNP in humans is still unknown. Therefore, we
      investigated the vasodilator actions of CNP in human forearm resistance vessels
      before and after inhibition of nitric oxide (NO) and then prostacyclin production
      and after inhibition of Ca(2+)-dependent potassium channel activation and NEP
      activity. Three separate studies were performed. In each study, forearm blood
      flow was recorded by venous occlusion plethysmography in 8 healthy nonsmoking
      subjects. Brachial artery infusion of CNP (70, 140, 280, and 560 ng per 100 mL
      forearm volume per minute) caused significant forearm vasodilation in all studies
      (forearm blood flow from 3.94 to 8.50 mL per 100 mL forearm volume per minute).
      Inhibition of the endogenous generation of NO by L-N(G)-monomethyl arginine (by
      use of the NO-clamp technique) did not block the maximal vasodilating effects of
      CNP (forearm blood flow from 3.69 to 6.93). In addition, when the cyclooxygenase
      system was inhibited by 600 mg of acetylsalicylic acid (aspirin) administered
      orally 30 minutes before start of measurements, the rise in forearm blood flow
      remained intact (forearm blood flow from 3.31 to 8.27 mL per 100 mL forearm
      volume per minute). However, inhibition of Ca(2+)-dependent potassium channels
      with tetraethylammonium chloride (0.1 mg per 100 mL forearm volume per minute)
      significantly attenuated vasodilation caused by CNP (forearm blood flow from 2.28
      to 3.06 mL per 100 mL forearm volume per minute), which suggests that CNP opens
      vascular potassium channels. Vasodilation to all doses of CNP was significantly
      increased when activity of NEP was blocked with thiorphan (30 nmol/min), which
      suggests that NEP activity limits vasodilation of CNP. CNP is a dilator of human
      resistance vessels that mediates its effects through hyperpolarization of the
      vessel wall independent of the NO and prostaglandin system. Inhibition of local
      NEP activity increases CNP bioavailability. This may be of relevance to
      cardiovascular disease, given that vascular tone is well balanced between NO and
      an endothelium-derived hyperpolarizing factor, which suggests that in
      pathological situations, impaired NO activity can be compensated for by enhanced
      endothelium-derived hyperpolarizing factor release to maintain vascular
      homeostasis.

PMID- 11304522
TI  - 8-iso-prostaglandin F(2alpha) increases expression of LOX-1 in JAR cells.
AB  - Lectinlike oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized
      LDL (ox-LDL), is proposed to be involved in endothelial dysfunction and in the
      pathogenesis of atherosclerosis. Preeclampsia is a pregnancy complication
      diagnosed by hypertension and proteinuria, characterized by endothelial
      dysfunction, and supposedly caused by compounds from hypoxic uteroplacental
      tissues. A feature of preeclampsia is formation of foam cells in maternal
      arterial walls of gestational tissue ("acute atherosis"). Oxidative stress is
      believed to play a role in the pathophysiology of preeclampsia. 8-iso
      prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in
      vivo, is biologically active in vitro, and is elevated in preeclamptic plasma and
      gestational tissue. In the present article, we hypothesized that 8-iso
      PGF(2alpha) could induce the expression of LOX-1 in trophoblastic cells (JAR). We
      demonstrated augmented cellular uptake of (125)I-tyraminylcellobiose ox-LDL in
      JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) versus control cells.
      Ligand blots revealed an increased binding of ox-LDL to LOX-1 in JAR cells
      incubated with 8-iso-PGF(2alpha) (10 micromol/L). Incubation with 8-iso
      PGF(2alpha) (10 micromol/L) also resulted in augmented LOX-1 protein levels
      (Western blots) and mRNA levels (Northern blots). JAR cells transfected with 3
      copies of a nuclear factor-kappaB binding site demonstrated dose-dependent
      activation of the reporter gene luciferase after incubation with 8-iso
      PGF(2alpha) (0 to 10 micromol/L). We also demonstrated increased accumulation of
      neutral fats in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) and ox
      LDL compared with controls by oil red O staining. We speculate a potential role
      of isoprostanes and LOX-1 in preeclampsia in the development of "acute atherosis"
      of gestational spiral arteries.

PMID- 11304523
TI  - Reduced uterine perfusion pressure during pregnancy in the rat is associated with
      increases in arterial pressure and changes in renal nitric oxide.
AB  - A reduction in nitric oxide (NO) synthesis has been suggested to play a role in
      pregnancy-induced hypertension. We have recently reported that normal pregnancy
      in the rat is associated with significant increases in whole-body NO production
      and renal protein expression of neuronal and inducible NO synthase. The purpose
      of this study was to determine whether whole-body and renal NO production is
      reduced in a rat model of pregnancy-induced hypertension produced by chronically
      reducing uterine perfusion pressure starting at day 14 of gestation. Chronic
      reductions in uterine perfusion pressure resulted in increases in arterial
      pressure of 20 to 25 mm Hg, decreases in renal plasma flow (<23%) and glomerular
      filtration rate (<40%), but no difference in urinary nitrite/nitrate excretion
      relative to control pregnant rats. In contrast, reductions in uterine perfusion
      pressure in virgin rats resulted in no significant effects on arterial pressure.
      Renal endothelial (<4%) and inducible (<11%) NO synthase protein expression did
      not decrease significantly in the chronically reduced uterine perfusion pressure
      rats relative to normal pregnant rats; however, significant reductions in
      neuronal NO synthase were observed (<30%). The results of this study indicate
      that the reduction in renal hemodynamics and the increase in arterial pressure
      observed in response to chronic decreases in uterine perfusion pressure in
      pregnant rats are associated with no change in whole-body NO production and a
      decrease in renal protein expression of neuronal NO synthase.

PMID- 11304524
TI  - Structural basis of the Na+/H+ exchanger regulatory factor PDZ1 interaction with
      the carboxyl-terminal region of the cystic fibrosis transmembrane conductance
      regulator.
AB  - The PDZ1 domain of the Na(+)/H(+) exchanger regulatory factor (NHERF) binds with
      nanomolar affinity to the carboxyl-terminal sequence QDTRL of the cystic fibrosis
      transmembrane conductance regulator (CFTR) and plays a central role in the
      cellular localization and physiological regulation of this chloride channel. The
      crystal structure of human NHERF PDZ1 bound to the carboxyl-terminal peptide
      QDTRL has been determined at 1.7-A resolution. The structure reveals the
      specificity and affinity determinants of the PDZ1-CFTR interaction and provides
      insights into carboxyl-terminal leucine recognition by class I PDZ domains. The
      peptide ligand inserts into the PDZ1 binding pocket forming an additional
      antiparallel beta-strand to the PDZ1 beta-sheet, and an extensive network of
      hydrogen bonds and hydrophobic interactions stabilize the complex. Remarkably,
      the guanido group of arginine at position -1 of the CFTR peptide forms two salt
      bridges and two hydrogen bonds with PDZ1 residues Glu(43) and Asn(22),
      respectively, providing the structural basis for the contribution of the
      penultimate amino acid of the peptide ligand to the affinity of the interaction.

PMID- 11304525
TI  - ACEII, a novel transcriptional activator involved in regulation of cellulase and
      xylanase genes of Trichoderma reesei.
AB  - A novel yeast-based method to isolate transcriptional activators was applied to
      clone regulators binding to the cellulase promoter cbh1 of the filamentous fungus
      Trichoderma reesei (Hypocrea jecorina). This led to the isolation of the
      cellulase activator ace2 encoding for a protein belonging to the class of zinc
      binuclear cluster proteins found exclusively in fungi. The DNA-binding domain of
      ACEII was expressed as a glutathione S-transferase fusion protein in Escherichia
      coli, and ACEII was shown to bind in vitro to the 5'-GGCTAATAA site present in
      the cbh1 promoter. This site also contains the proposed binding sequence of the
      xylanase activator XlnR of Aspergillus niger. Mutation of the GGC triplet
      abolished ACEII binding. The function of ACEII was studied by analyzing the
      effects of ace2 deletion in the hypercellulolytic T. reesei strain ALKO2221.
      Deletion of the ace2 gene led to lowered induction kinetics of mRNAs encoding the
      major cellulases cellobiohydrolases I and II and endoglucanases I and II and to
      30-70% reduced cellulase activity when the fungus was grown on medium containing
      Solka floc cellulose. The expression level of the gene encoding xylanase was also
      affected. ace2 deletion led to lowered xyn2 expression in cellulose-induced
      cultivation. Cellulase induction by sophorose was not affected by ace2 deletion.

PMID- 11304526
TI  - Phosphatidylinositol 4,5-bisphosphate mediates Ca2+-induced platelet alpha
      granule secretion: evidence for type II phosphatidylinositol 5-phosphate 4-kinase
      function.
AB  - To understand the molecular basis of granule release from platelets, we examined
      the role of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) in alpha
      granule secretion. Streptolysin O-permeabilized platelets synthesized
      PtdIns(4,5)P(2) when incubated in the presence of ATP. Incubation of streptolysin
      O-permeabilized platelets with phosphatidylinositol-specific phospholipase C
      reduced PtdIns(4,5)P(2) levels and resulted in a dose- and time-dependent
      inhibition of Ca(2+)-induced alpha-granule secretion. Exogenously added
      PtdIns(4,5)P(2) inhibited alpha-granule secretion, with 80% inhibition at 50
      microm PtdIns(4,5)P(2). Nanomolar concentrations of wortmannin, 33.3 microm
      LY294002, and antibodies directed against PtdIns 3-kinase did not inhibit Ca(2+)
      induced alpha-granule secretion, suggesting that PtdIns 3-kinase is not involved
      in alpha-granule secretion. However, micromolar concentrations of wortmannin
      inhibited both PtdIns(4,5)P(2) synthesis and alpha-granule secretion by
      approximately 50%. Antibodies directed against type II phosphatidylinositol
      phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) also inhibited both
      PtdIns(4,5)P(2) synthesis and Ca(2+)-induced alpha-granule secretion by
      approximately 50%. These antibodies inhibited alpha-granule secretion only when
      added prior to ATP exposure and not when added following ATP exposure, prior to
      Ca(2+)-mediated triggering. The inhibitory effects of micromolar wortmannin and
      anti-type II phosphatidylinositol-phosphate kinase antibodies were additive.
      These results show that PtdIns(4,5)P(2) mediates platelet alpha-granule secretion
      and that PtdIns(4,5)P(2) synthesis required for Ca(2+)-induced alpha-granule
      secretion involves the type II phosphatidylinositol 5-phosphate 4-kinase
      dependent pathway.

PMID- 11304527
TI  - In vivo formation of a human beta-globin locus control region core element
      requires binding sites for multiple factors including GATA-1, NF-E2, erythroid
      Kruppel-like factor, and Sp1.
AB  - The active elements of the beta-globin locus control region (LCR) are located
      within domains of unique chromatin structure. These nuclease hypersensitive sites
      (HSs) are characterized by high DNase I sensitivity, erythroid specificity,
      similar nucleosomal structure, and evolutionarily conserved clusters of cis
      acting elements that are required for the formation and function of the core
      elements. To determine the requirements for HS core formation in the setting of
      nuclear chromatin, we constructed a series of artificial HS cores containing
      binding sites for GATA-1, NF-E2, and Sp1. In contrast to the results of previous
      in vitro experiments, we found that when constructs were stably integrated in
      mouse erythroleukemia cells the binding sites for NF-E2, GATA-1, or Sp1 alone or
      in any combination were unable to form core HS structures. We subsequently
      identified two new cis-acting elements from the LCR HS4 core that, when combined
      with the NF-E2, Sp1, and tandem inverted GATA elements, result in core structure
      formation. Both new cis-acting elements bind Sp1, and one binds erythroid Kruppel
      like factor (EKLF). We conclude that in vivo beta-globin LCR HS core formation is
      more complex than previously thought and that several factors are required for
      this process to occur.

PMID- 11304528
TI  - Oxidation of a tetrameric nonphenolic lignin model compound by lignin peroxidase.
AB  - The present study maps the active site of lignin peroxidase in respect to
      substrate size using either fungal or recombinant wild type, as well as mutated,
      recombinant lignin peroxidases. A nonphenolic tetrameric lignin model was
      synthesized that contains beta-O-4 linkages. The fungal and recombinant wild type
      lignin peroxidase both oxidized the tetrameric model forming four products. The
      four products were identified by mass spectral analyses and compared with
      synthetic standards. They were identified as tetrameric, trimeric, dimeric, and
      monomeric carbonyl compounds. All four of these products were also formed from
      single turnover experiments. This indicates that lignin peroxidase is able to
      attack any of the C(alpha)-C(beta) linkages in the tetrameric compound and that
      the substrate-binding site is well exposed. Mutation of the recombinant lignin
      peroxidase (isozyme H8) in the heme access channel, which is relatively
      restricted and was previously proposed to be the veratryl alcohol-binding site
      (E146S), had little effect on the oxidation of the tetramer. In contrast,
      mutation of a Trp residue (W171S) in the alternate proposed substrate-binding
      site completely inhibited the oxidation of the tetrameric model. These results
      are consistent with lignin peroxidase having an exposed active site capable of
      directly interacting with the lignin polymer without the advent of low molecular
      weight mediators.

PMID- 11304529
TI  - Pentosan polysulfate as an inhibitor of extracellular HIV-1 Tat.
AB  - HIV-1 Tat protein, released from HIV-infected cells, may act as a pleiotropic
      heparin-binding growth factor. From this observation, extracellular Tat has been
      implicated in the pathogenesis of AIDS and of AIDS-associated pathologies. Here
      we demonstrate that the heparin analog pentosan polysulfate (PPS) inhibits the
      interaction of glutathione S-transferase (GST)-Tat protein with heparin
      immobilized to a BIAcore sensor chip. Competition experiments showed that Tat-PPS
      interaction occurs with high affinity (K(d) = 9.0 nm). Also, GST.Tat prevents the
      binding of [(3)H]heparin to GST.Tat immobilized to glutathione-agarose beads. In
      vitro, PPS inhibits GST.Tat internalization and, consequently, HIV-1 long
      terminal repeat transactivation in HL3T1 cells. Also, PPS inhibits cell surface
      interaction and mitogenic activity of GST.Tat in murine adenocarcinoma T53 Tat
      less cells. In all assays, PPS exerts its Tat antagonist activity with an ID(50)
      equal to approximately 1.0 nm. In vivo, PPS inhibits the neovascularization
      induced by GST.Tat or by Tat-overexpressing T53 cells in the chick embryo
      chorioallantoic membrane. In conclusion, PPS binds Tat protein and inhibits its
      cell surface interaction, internalization, and biological activity in vitro and
      in vivo. PPS may represent a prototypic molecule for the development of novel Tat
      antagonists with therapeutic implications in AIDS and AIDS-associated
      pathologies, including Kaposi's sarcoma.

PMID- 11304530
TI  - An araC-controlled bacterial cre expression system to produce DNA minicircle
      vectors for nuclear and mitochondrial gene therapy.
AB  - The presence of CpG motifs and their associated sequences in bacterial DNA causes
      an immunotoxic response following the delivery of these plasmid vectors into
      mammalian hosts. We describe a biotechnological approach to the elimination of
      this problem by the creation of a bacterial cre recombinase expression system,
      tightly controlled by the arabinose regulon. This permits the Cre-mediated and 
      directed excision of the entire bacterial vector sequences from plasmid
      constructs to create supercoiled gene expression minicircles for gene therapy.
      Minicircle yields using standard culture volumes are sufficient for most in vitro
      and in vivo applications whereas minicircle expression in vitro is significantly
      increased over standard plasmid transfection. By the simple expedient of removing
      the bacterial DNA complement, we significantly reduce the size and CpG content of
      these expression vectors, which should also reduce DNA-induced inflammatory
      responses in a dose-dependent manner. We further describe the generation of
      minicircle expression vectors for mammalian mitochondrial gene therapy, for which
      no other vector systems currently exist. The removal of bacterial vector
      sequences should permit appropriate transcription and correct transcriptional
      cleavage from the mitochondrial minicircle constructs in a mitochondrial
      environment and brings the realization of mitochondrial gene therapy a step
      closer.

PMID- 11304531
TI  - Parallel regulation of mitogen-activated protein kinase kinase 3 (MKK3) and MKK6
      in Gq-signaling cascade.
AB  - Heterotrimeric G protein G(q) stimulates the activity of p38 mitogen-activated
      protein kinase (MAPK) in mammalian cells. To investigate the signaling mechanism
      whereby alpha and betagamma subunits of G(q) activate p38 MAPK, we introduced
      kinase-deficient mutants of mitogen-activated protein kinase kinase 3 (MKK3),
      MKK4, and MKK6 into human embryonal kidney 293 cells. The activation of p38 MAPK
      by Galpha(q) and Gbetagamma was blocked by kinase-deficient MKK3 and MKK6 but not
      by kinase-deficient MKK4. In addition, Galpha(q) and Gbetagamma stimulated MKK3
      and MKK6 activities. The MKK3 and MKK6 activations by Galpha(q), but not by
      Gbetagamma, were dependent on phospholipase C and c-Src. Galpha(q) stimulated
      MKK3 in a Rac- and Cdc42-dependent manner and MKK6 in a Rho-dependent manner. On
      the other hand, Gbetagamma activated MKK3 in a Rac- and Cdc42-dependent manner
      and MKK6 in a Rho-, Rac-, and Cdc42-dependent manner. Gbetagamma-induced MKK3 and
      MKK6 activations were dependent on a tyrosine kinase other than c-Src. These
      results suggest that Galpha(q) and Gbetagamma stimulate the activity of p38 MAPK
      by regulating MKK3 and MKK6 through parallel signaling pathways.

PMID- 11304532
TI  - A recycling pathway for resecretion of internalized apolipoprotein E in liver
      cells.
AB  - We have investigated the recycling of apoE in livers of apoE(-)/- mice
      transplanted with wild type bone marrow (apoE(+/+) --> apoE(-)/-), a model in
      which circulating apoE is derived exclusively from macrophages. Nascent Golgi
      lipoproteins were recovered from livers of apoE(+/+) --> apoE(-)/- mice 8 weeks
      after transplantation. ApoE was identified with nascent d < 1.006 and with d
      1.006-1.210 g/ml lipoproteins at a level approximately 6% that of nascent
      lipoproteins from C57BL/6 mice. Hepatocytes from apoE(+/+) --> apoE(-)/- mice
      were isolated and cultured in media free of exogenous apoE. ApoE was found in the
      media primarily on the d < 1.006 g/ml fraction, indicating a resecretion of
      internalized apoprotein. Secretion of apoE from C57BL/6 hepatocytes was
      consistent with constitutive production, whereas the majority of apoE secreted
      from apoE(+/+) --> apoE(-)/- hepatocytes was recovered in the last 24 h of
      culture. This suggests that release may be triggered by accumulation of an
      acceptor, such as very low density lipoproteins, in the media. In agreement with
      the in vivo data, total recovery of apoE from apoE(+/+) --> apoE(-)/- hepatocytes
      was approximately 6% that of the apoE recovered from C57BL/6 hepatocytes. Since
      plasma apoE levels in the transplanted mice are approximately 10% of control
      levels, the findings indicate that up to 60% of the internalized apoE may be
      reutilized under physiologic conditions. These studies provide definitive
      evidence for the sparing of apoE and its routing through the secretory pathway
      and demonstrate that internalized apoE can be resecreted in a quantitatively
      significant fashion.

PMID- 11304533
TI  - Histone hyperacetylation induced by histone deacetylase inhibitors is not
      sufficient to cause growth inhibition in human dermal fibroblasts.
AB  - Use of specific histone deacetylase inhibitors has revealed critical roles for
      the histone deacetylases (HDAC) in controlling proliferation. Although many
      studies have correlated the function of HDAC inhibitors with the hyperacetylation
      of histones, few studies have specifically addressed whether the accumulation of
      acetylated histones, caused by HDAC inhibitor treatment, is responsible for
      growth inhibition. In the present study we show that HDAC inhibitors cause growth
      inhibition in normal and transformed keratinocytes but not in normal dermal
      fibroblasts. This was despite the observation that the HDAC inhibitor, suberic
      bishydroxamate (SBHA), caused a kinetically similar accumulation of
      hyperacetylated histones. This cell type-specific response to SBHA was not due to
      the inactivation of SBHA by fibroblasts, nor was it due to differences in the
      expression of specific HDAC family members. Remarkably, overexpression of HDACs
      1, 4, and 6 in normal human fibroblasts resulted in cells that could be growth
      inhibited by SBHA. These data suggest that, although histone acetylation is a
      major target for HDAC inhibitors, the accumulation of hyperacetylated histones is
      not sufficient to cause growth inhibition in all cell types. This suggests that
      growth inhibition, caused by HDAC inhibitors, may be the culmination of histone
      hyperacetylation acting in concert with other growth regulatory pathways.

PMID- 11304535
TI  - Cyclin-dependent kinase 2 nucleocytoplasmic translocation is regulated by
      extracellular regulated kinase.
AB  - Activation of cyclin-dependent kinase 2 (CDK2)-cyclin E in the late G(1) phase of
      the cell cycle is important for transit into S phase. In Chinese hamster
      embryonic fibroblasts (IIC9) phosphatidylinositol 3-kinase and ERK regulate alpha
      thrombin-induced G(1) transit by their effects on cyclin D1 protein accumulation
      (Phillips-Mason, P. J., Raben, D. M., and Baldassare, J. J. (2000) J. Biol. Chem.
      275, 18046-18053). Here, we show that ERK also affects CDK2-cyclin E activation
      by regulating the subcellular localization of CDK2. Ectopic expression of cyclin
      E rescues the inhibition of alpha-thrombin-induced activation of CDK2-cyclin E
      and transit into S phase brought about by treatment of IIC9 cells with LY29004, a
      selective inhibitor of mitogen stimulation of phosphatidylinositol 3-kinase
      activity. However, cyclin E expression is ineffectual in rescuing these effects
      when ERK activation is blocked by treatment with PD98059, a selective inhibitor
      of MEK activation of ERK. Investigation into the mechanistic reasons for this
      difference found the following. 1) Although treatment with LY29004 inhibits alpha
      thrombin-stimulated nuclear localization, ectopic expression of cyclin E rescues
      CDK2 translocation. 2) In contrast to treatment with LY29004, ectopic expression
      of cyclin E fails to restore alpha-thrombin-stimulated nuclear CDK2 translocation
      in IIC9 cells treated with PD98059. 3) CDK2-cyclin E complexes are not affected
      by treatment with either inhibitor. These data indicate that, in addition to its
      effects on cyclin D1 expression, ERK activity is an important controller of the
      translocation of CDK2 into the nucleus where it is activated.

PMID- 11304534
TI  - Characterization of a novel airway epithelial cell-specific short chain alcohol
      dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is
      involved in the metabolism of retinol.
AB  - Multiple retinoic acid responsive cDNAs were isolated from a high density cDNA
      microarray membrane, which was developed from a cDNA library of human
      tracheobronchial epithelial cells. Five selected cDNA clones encoded the sequence
      of the same novel gene. The predicted open reading frame of the novel gene
      encoded a protein of 319 amino acids. The deduced amino acid sequence contains
      four motifs that are conserved in the short-chain alcohol dehydrogenase/reductase
      (SDR) family of proteins. The novel gene shows the greatest homology to a group
      of dehydrogenases that can oxidize retinol (retinol dehydrogenases). The mRNA of
      the novel gene was found in trachea, colon, tongue, and esophagus. In situ
      hybridization of airway tissue sections demonstrated epithelial cell-specific
      gene expression, especially in the ciliated cell type. Both all-trans-retinoic
      acid and 9-cis-retinoic acid were able to elevate the expression of the novel
      gene in primary human tracheobronchial epithelial cells in vitro. This elevation
      coincided with an enhanced retinol metabolism in these cultures. COS cells
      transfected with an expression construct of the novel gene were also elevated in
      the metabolism of retinol. The results suggested that the novel gene represents a
      new member of the SDR family that may play a critical role in retinol metabolism
      in airway epithelia as well as in other epithelia of colon, tongue, and
      esophagus.

PMID- 11304536
TI  - SMRTE inhibits MEF2C transcriptional activation by targeting HDAC4 and 5 to
      nuclear domains.
AB  - The silencing mediator for retinoic acid and thyroid hormone receptors (SMRT)
      mediates transcriptional repression by recruiting histone deacetylases (HDACs) to
      the DNA-bound nuclear receptor complex. The full-length SMRT (SMRTe) contains an
      N-terminal sequence that is highly conserved to the nuclear receptor corepressor
      N-CoR. To date, little is known about the activity and function of the full
      length SMRTe protein, despite extensive studies on separated receptor interaction
      and transcriptional repression domains. Here we show that SMRTe inhibits MEF2C
      transcriptional activation by targeting selective HDACs to unique subnuclear
      domains. Indirect immunofluorescence studies with anti-SMRTe antibody reveal
      discrete cytoplasmic and nuclear speckles, which contain RARalpha in an RA
      sensitive manner. Formation of the SMRTe nuclear speckles results in recruitment
      of several class I and class II HDACs to these subnuclear domains in a process
      depending on HDAC enzymatic activity. Intriguingly, although HDAC4 is located
      primarily in the cytoplasm, coexpression of SMRTe dramatically translocates HDAC4
      from the cytoplasm into the nucleus, where HDAC4 prevents MEF2C from activating
      muscle differentiation. SMRTe also translocates HDAC5 from diffusive nucleoplasm
      into discrete nuclear domains. Accordingly, SMRTe synergizes with HDAC4 and 5 to
      inhibit MEF2C transactivation of target promoter, suggesting that nuclear domain
      targeting of HDAC4/5 may be important in preventing muscle cell differentiation.
      These results highlight an unexpected new function of the nuclear receptor
      corepressor SMRTe for its role in regulating cellular trafficking of nuclear
      receptor and selective HDACs that may play an important role in regulation of
      cell growth and differentiation.

PMID- 11304537
TI  - Nonstructural 3 protein of hepatitis C virus triggers an oxidative burst in human
      monocytes via activation of NADPH oxidase.
AB  - It has been shown that oxidative stress occurs in chronic hepatitis C. Release of
      reactive oxygen species (ROS) from sequestered phagocytes and activated resident
      macrophages represents the predominant component of oxidative stress in the
      liver. However, little is known about the ability of the monocyte to produce ROS
      in response to protein of hepatitis C virus. In this study, we investigated the
      ROS production in human monocytes stimulated by several viral proteins of
      hepatitis C virus. Human monocytes from healthy blood donors were incubated with
      recombinant viral protein: Core, NS3, NS4, and NS5. ROS production was measured
      by chemiluminescence. Only NS3 triggered ROS production in human monocytes.
      Generated ROS were mainly the anion superoxide. NS3 also induced a rapid and
      transient increase in intracellular calcium concentration measured by a video
      digital microscopy technique. By using different metabolic inhibitors, we showed
      that ROS production requires calcium influx, tyrosine kinases, and the stress
      activated protein kinase, p38. The study of p47(PHOX) phosphorylation and
      translocation showed that NADPH oxidase was activated and involved in ROS
      production induced by NS3. In a second experiment, NS3 inhibited the oxidative
      burst induced by phorbol 12-myristate 13-acetate. These results indicate that NS3
      activates NADPH oxidase and modulates ROS production, which may be involved in
      the natural history of hepatitis C infection.

PMID- 11304538
TI  - Cell type-specific differences in glycosaminoglycans modulate the biological
      activity of a heparin-binding peptide (RKRLQVQLSIRT) from the G domain of the
      laminin alpha1 chain.
AB  - AG73 (RKRLQVQLSIRT), a peptide from the G domain of the laminin alpha1 chain, has
      diverse biological activities with different cell types. The heparan sulfate side
      chains of syndecan-1 on human salivary gland cells were previously identified as
      the cell surface ligand for AG73. We used homologous peptides from the other
      laminin alpha-chains (A2G73-A5G73) to determine whether the bioactivity of the
      AG73 sequence is conserved. Human salivary gland cells and a mouse melanoma cell
      line (B16F10) both bind to the peptides, but cell attachment was inhibited by
      glycosaminoglycans, modified heparin, and sized heparin fragments in a cell type
      specific manner. In other assays, AG73, but not the homologous peptides,
      inhibited branching morphogenesis of salivary glands and B16F10 network formation
      on Matrigel. We identified residues critical for AG73 bioactivity using peptides
      with amino acid substitutions and truncations. Fewer residues were critical for
      inhibiting branching morphogenesis (XKXLXVXXXIRT) than those required to inhibit
      B16F10 network formation on Matrigel (N-terminal XXRLQVQLSIRT). In addition,
      surface plasmon resonance analysis identified the C-terminal IRT of the sequence
      to be important for heparin binding. Structure-based sequence alignment predicts
      AG73 in a beta-sheet with the N-terminal K (Lys(2)) and the C-terminal R
      (Arg(10)) on the surface of the G domain. In conclusion, we have determined that
      differences in cell surface glycosaminoglycans and differences in the amino acids
      in AG73 recognized by cells modulate the biological activity of the peptide and
      provide a mechanism to explain its cell-specific activities.

PMID- 11304539
TI  - Deuterium isotope effects during carbon-hydrogen bond cleavage by trimethylamine
      dehydrogenase. Implications for mechanism and vibrationally assisted hydrogen
      tunneling in wild-type and mutant enzymes.
AB  - His-172 and Tyr-169 are components of a triad in the active site of
      trimethylamine dehydrogenase (TMADH) comprising Asp-267, His-172, and Tyr-169.
      Stopped-flow kinetic studies with trimethylamine as substrate have indicated that
      mutation of His-172 to Gln reduces the limiting rate constant for flavin
      reduction approximately 10-fold (Basran, J., Sutcliffe, M. J., Hille, R., and
      Scrutton, N. S. (1999) Biochem. J. 341, 307-314). A kinetic isotope effect (KIE =
      k(H)/k(D)) accompanies flavin reduction by H172Q TMADH, the magnitude of which
      varies significantly with solution pH. With trimethylamine, flavin reduction by
      H172Q TMADH is controlled by a single macroscopic ionization (pK(a) = 6.8 +/-
      0.1). This ionization is perturbed (pK(a) = 7.4 +/- 0.1) in reactions with
      perdeuterated trimethylamine and is responsible for the apparent variation in the
      KIE with solution pH. At pH 9.5, where the functional group controlling flavin
      reduction is fully ionized, the KIE is independent of temperature in the range
      277-297 K, consistent with vibrationally assisted hydrogen tunneling during
      breakage of the substrate C-H bond. Y169F TMADH is approximately 4-fold more
      compromised than H172Q TMADH for hydrogen transfer, which occurs non-classically.
      Studies with Y169F TMADH suggest partial thermal excitation of substrate prior to
      hydrogen tunneling by a vibrationally assisted mechanism. Our studies illustrate
      the varied effects of compromising mutations on tunneling regimes in enzyme
      molecules.

PMID- 11304540
TI  - Transcription regulation and protein subcellular localization of the truncated
      basic hair keratin hHb1-DeltaN in human breast cancer cells.
AB  - An aberrant truncated hHb1 hair keratin transcript, named hHb1-DeltaN, was
      previously identified in breast carcinomas. No normal tissue tested so far,
      including hairy skin, expressed hHb1-DeltaN, indicating that hHb1-DeltaN is
      related to carcinogenesis. In the present study, we investigated the mechanism by
      which such truncated transcript was generated in breast cancer cell lines. We
      found that hHb1-DeltaN transcription is initiated at an unusual cryptic promoter
      within the fourth intron of the hHb1 gene and is dependent on two proximal Sp1
      binding sites for its baseline activity. Moreover, hHb1-DeltaN transcription is
      increased in response to DNA demethylation by the 5-aza-2'-deoxycytidine drug.
      This induction is dependent on protein neosynthesis, indicating that an
      additional factor is required. In addition, we showed that the hHb1-DeltaN
      transcript is translated in vivo as a truncated hHb1 protein that is missing the
      270 amino-terminal residues. The hHb1-DeltaN protein exhibits a filament pattern
      throughout the cytoplasm and partially co-localizes with cytokeratin filaments,
      indicating its participation in the cytoskeleton network. hHb1-DeltaN might alter
      the adhesive properties of cancer cells.

PMID- 11304541
TI  - Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells
      following phorbol ester treatment.
AB  - Interferon regulatory factor-2 (IRF-2) is a transcription factor of the IRF
      family that represses interferon-mediated gene expression. In the present study,
      we show that human monocytic U937 cells express truncated forms of IRF-2
      containing the DNA binding domain but lacking much of the C-terminal regulatory
      domain. U937 cells are shown to respond to phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA) to induce expression of histone acetylases
      p300 and p300/CBP-associated factor (PCAF). In addition, TPA treatment led to the
      appearance of full-length IRF-2, along with a reduction of the truncated protein.
      Interestingly, full-length IRF-2 in TPA-treated U937 cells occurred as a complex
      with p300 as well as PCAF and was itself acetylated. Consistent with these
      results, recombinant IRF-2 was acetylated by p300 and to a lesser degree by PCAF
      in vitro. Another IRF member, IRF-1, an activator of interferon-mediated
      transcription, was also acetylated in vitro by these acetylases. Finally, we
      demonstrate that the addition of IRF-2 but not IRF-1 inhibits core histone
      acetylation by p300 in vitro. The addition of IRF-2 also inhibited acetylation of
      nucleosomal histones in TPA-treated U937 cells. Acetylated IRF-2 may affect local
      chromatin structure in vivo by inhibiting core histone acetylation and may serve
      as a mechanism by which IRF-2 negatively regulates interferon-inducible
      transcription.

PMID- 11304542
TI  - Alleviation of a defect in protein folding by increasing the rate of subunit
      assembly.
AB  - Understanding the nature of protein grammar is critical because amino acid
      substitutions in some proteins cause misfolding and aggregation of the mutant
      protein resulting in a disease state. Amino acid substitutions in phage P22 coat
      protein, known as tsf (temperature-sensitive folding) mutations, cause folding
      defects that result in aggregation at high temperatures. We have isolated global
      su (suppressor) amino acid substitutions that alleviate the tsf phenotype in coat
      protein (Aramli, L. A., and Teschke, C. M. (1999) J. Biol. Chem. 274, 22217
      22224). Unexpectedly, we found that a global su amino acid substitution in tsf
      coat proteins made aggregation worse and that the tsf phenotype was suppressed by
      increasing the rate of subunit assembly, thereby decreasing the concentration of
      aggregation-prone folding intermediates.

PMID- 11304543
TI  - A membrane-distal segment of the integrin alpha IIb cytoplasmic domain regulates
      integrin activation.
AB  - Previous evidence suggests that interactions between integrin cytoplasmic domains
      regulate integrin activation. We have constructed and validated recombinant
      structural mimics of the heterodimeric alpha(IIb)beta(3) cytoplasmic domain. The
      mimics elicited polyclonal antibodies that recognize a combinatorial epitope(s)
      formed in mixtures of the alpha(IIb) and beta(3) cytoplasmic domains but not
      present in either isolated tail. This epitope(s) is present within intact
      alpha(IIb)beta(3), indicating that interaction between the tails can occur in the
      native integrin. Furthermore, the combinatorial epitope(s) is also formed by
      introducing the activation-blocking beta(3)(Y747A) mutation into the beta(3)
      tail. A membrane-distal heptapeptide sequence in the alpha(IIb) tail
      ((997)RPPLEED) is responsible for this effect on beta(3). Membrane-permeant
      palmitoylated peptides, containing this alpha(IIb) sequence, specifically blocked
      alpha(IIb)beta(3) activation in platelets. Thus, this region of the alpha(IIb)
      tail causes the beta(3) tail to resemble that of beta(3)(Y747A) and suppresses
      activation of the integrin.

PMID- 11304544
TI  - Characterization of recombinant HPV6 and 11 E1 helicases: effect of ATP on the
      interaction of E1 with E2 and mapping of a minimal helicase domain.
AB  - To better characterize the enzymatic activities required for human papillomavirus
      (HPV) DNA replication, the E1 helicases of HPV types 6 and 11 were produced using
      a baculovirus expression system. The purified wild type proteins and a version of
      HPV11 E1 lacking the N-terminal 71 amino acids, which was better expressed, were
      found to be hexameric over a wide range of concentrations and to have helicase
      and ATPase activities with relatively low values for K(m)(ATP) of 12 microm for
      HPV6 E1 and 6 microm for HPV11 E1. Interestingly, the value of K(m)(ATP) was
      increased 7-fold in the presence of the E2 transactivation domain. In turn, ATP
      was found to perturb the co-operative binding of E1 and E2 to DNA. Mutant and
      truncated versions of in vitro translated E1 were used to identify a minimal
      ATPase domain composed of the C-terminal 297 amino acids. This fragment was
      expressed, purified, and found to be fully active in ATP hydrolysis, single
      stranded DNA binding, and unwinding assays, despite lacking the minimal origin
      binding domain.

PMID- 11304545
TI  - Galactan biosynthesis in Mycobacterium tuberculosis. Identification of a
      bifunctional UDP-galactofuranosyltransferase.
AB  - The cell wall of Mycobacterium tuberculosis and related genera is unique among
      prokaryotes, consisting of a covalently bound complex of mycolic acids, D
      arabinan and D-galactan, which is linked to peptidoglycan via a special linkage
      unit consisting of Rhap-(1-->3)-GlcNAc-P. Information concerning the biosynthesis
      of this entire polymer is now emerging with the promise of new drug targets
      against tuberculosis. Accordingly, we have developed a galactosyltransferase
      assay that utilizes the disaccharide neoglycolipid acceptors beta-d-Galf-(1-->5)
      beta-D-Galf-O-C(10:1) and beta-D-Galf-(1-->6)-beta-D-Galf-O-C(10:1), with UDP-Gal
      in conjunction with isolated membranes. Chemical analysis of the subsequent
      reaction products established that the enzymatically synthesized products
      contained both beta-D-Galf linkages ((1-->5) and (1-->6)) found within the
      mycobacterial cell, as well as in an alternating (1-->5) and (1-->6) fashion
      consistent with the established structure of the cell wall. Furthermore, through
      a detailed examination of the M. tuberculosis genome, we have shown that the gene
      product of Rv3808c, now termed glfT, is a novel UDP-galactofuranosyltransferase.
      This enzyme possesses dual functionality in performing both (1-->5) and (1-->6)
      galactofuranosyltransferase reactions with the above neoglycolipid acceptors,
      using membranes isolated from the heterologous host Escherichia coli expressing
      Rv3808c. Thus, at a biochemical and genetic level, the polymerization of the
      galactan region of the mycolyl-arabinogalactan complex has been defined, allowing
      the possibility of further studies toward substrate recognition and catalysis and
      assay development. Ultimately, this may also lead to a more rational approach to
      drug design to be explored in the context of mycobacterial infections.

PMID- 11304546
TI  - Integrin-linked kinase (ILK) binding to paxillin LD1 motif regulates ILK
      localization to focal adhesions.
AB  - Paxillin is a focal adhesion adapter protein involved in integrin signaling.
      Paxillin LD motifs bind several focal adhesion proteins including the focal
      adhesion kinase, vinculin, the Arf-GTPase-activating protein paxillin-kinase
      linker, and the newly identified actin-binding protein actopaxin. Microsequencing
      of peptides derived from a 50-kDa paxillin LD1 motif-binding protein revealed
      100% identity with integrin-linked kinase (ILK)-1, a serine/threonine kinase that
      has been implicated in integrin, growth factor, and Wnt signaling pathways.
      Cloning of ILK from rat smooth muscle cells generated a cDNA that exhibited 99.6%
      identity at the amino acid level with human ILK-1. A monoclonal antibody raised
      against a region of the carboxyl terminus of ILK, which is identical in rat and
      human ILK-1 protein, recognized a 50-kDa protein in all cultured cells and
      tissues examined. Binding experiments showed that ILK binds directly to the
      paxillin LD1 motif in vitro. Co-immunoprecipitation from fibroblasts confirmed
      that the association between paxillin and ILK occurs in vivo in both adherent
      cells and cells in suspension. Immunofluorescence microscopy of fibroblasts
      demonstrated that endogenous ILK as well as transfected green fluorescent protein
      ILK co-localizes with paxillin in focal adhesions. Analysis of the deduced amino
      acid sequence of ILK identified a paxillin-binding subdomain in the carboxyl
      terminus of ILK. In contrast to wild-type ILK, paxillin-binding subdomain mutants
      of ILK were unable to bind to the paxillin LD1 motif in vitro and failed to
      localize to focal adhesions. Thus, paxillin binding is necessary for efficient
      focal adhesion targeting of ILK and may therefore impact the role of ILK in
      integrin-mediated signal transduction events.

PMID- 11304547
TI  - The importance of structural transitions of the switch II region for the
      functions of elongation factor Tu on the ribosome.
AB  - Elongation factor Tu (EF-Tu) undergoes a large conformational transition when
      switching from the GTP to GDP forms. Structural changes in the switch I and II
      regions in the G domain are particularly important for this rearrangement. In the
      switch II region, helix alpha2 is flanked by two glycine residues: Gly(83) in the
      consensus element DXXG at the N terminus and Gly(94) at the C terminus. The role
      of helix alpha2 was studied by pre-steady-state kinetic experiments using
      Escherichia coli EF-Tu mutants where either Gly(83), Gly(94), or both were
      replaced with alanine. The G83A mutation slows down the association of the
      ternary complex EF-Tu.GTP.aminoacyl-tRNA with the ribosome and abolishes the
      ribosome-induced GTPase activity of EF-Tu. The G94A mutation strongly impairs the
      conformational change of EF-Tu from the GTP- to the GDP-bound form and
      decelerates the dissociation of EF-Tu.GDP from the ribosome. The behavior of the
      double mutant is dominated by the G83A mutation. The results directly relate
      structural transitions in the switch II region to specific functions of EF-Tu on
      the ribosome.

PMID- 11304548
TI  - The interactions of yeast SWI/SNF and RSC with the nucleosome before and after
      chromatin remodeling.
AB  - Interactions of the yeast chromatin-remodeling complexes SWI/SNF and RSC with
      nucleosomes were probed using site-specific DNA photoaffinity labeling. 5 S rDNA
      was engineered with photoreactive nucleotides incorporated at different sites in
      DNA to scan for the subunits of SWI/SNF in close proximity to DNA when SWI/SNF is
      bound to the 5 S nucleosome or to the free 5 S rDNA. The Swi2/Snf2 and Snf6
      subunits of SWI/SNF were efficiently cross-linked at several positions in the
      nucleosome, whereas only Snf6 was efficiently cross-linked when SWI/SNF was bound
      to free DNA. DNA photoaffinity labeling of RSC showed that the Rsc4 subunit is in
      close proximity to nucleosomal DNA and not when RSC is bound to free DNA. After
      remodeling, the Swi2/Snf2 and Rsc4 subunits are no longer detected near the
      nucleosomal DNA and are evidently displaced from the surface of the nucleosome,
      indicating significant changes in SWI/SNF and RSC contacts with DNA after
      remodeling.

PMID- 11304549
TI  - Cytokines regulate proteolysis in major histocompatibility complex class II
      dependent antigen presentation by dendritic cells.
AB  - Endo/lysosomal proteases control two key events in antigen (Ag) presentation: the
      degradation of protein Ag and the generation of peptide-receptive major
      histocompatibility complex (MHC) class II molecules. Here we show that the
      proinflammatory cytokines tumor necrosis factor alpha and interleukin (IL)-1beta
      rapidly increase the activity of cathepsin (cat) S and catB in human dendritic
      cells (DCs). As a consequence, a wave of MHC class II sodium dodecyl sulfate
      stable dimer formation ensues in a catS-dependent fashion. In contrast, the
      antiinflammatory cytokine IL-10 renders DCs incapable of upregulating catS and
      catB activity and in fact, attenuates the level of both enzymes. Suppressed catS
      and catB activity delays MHC class II sodium dodecyl sulfate stable dimer
      formation and impairs Ag degradation. In DCs exposed to tetanus toxoid, IL-10
      accordingly reduces the number of MHC class II-peptide complexes accessible to
      tetanus toxoid-specific T cell receptors, as analyzed by measuring T cell
      receptor downregulation in Ag-specific T cell clones. Thus, the control of
      protease activity by pro- and antiinflammatory cytokines is an essential feature
      of the Ag presentation properties of DCs.

PMID- 11304550
TI  - The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell
      receptor families.
AB  - To define the phenotype and T cell receptor (TCR) repertoire of CD1d-dependent T
      cells, we compared the populations of T cells that persisted in major
      histocompatibility complex (MHC)-deficient mice, which lack mainstream T cells,
      with those from MHC/CD1d doubly deficient mice, which lack both mainstream and
      CD1d-dependent T cells. Surprisingly, up to 80% of the CD1d-dependent T cells
      were stained by tetramers of CD1d/alpha-galactosylceramide, which specifically
      identify the previously described CD1d autoreactive Valpha14-Jalpha18/Vbeta8
      natural killer (NK) T cells. Furthermore, zooming in on the CD1d-dependent non
      Valpha14 T cells, we found that, like Valpha14 NK T cells, they mainly expressed
      recurrent, CD1d autoreactive TCR families and had a natural memory phenotype.
      Thus, CD1d-restricted T cells differ profoundly from MHC-peptide-specific T cells
      by their predominant use of autoreactive and semiinvariant, rather than naive and
      diverse, TCRs. They more closely resemble other lineages of innate lymphocytes
      such as B-1 B cells, gammadelta T cells, and NK cells, which express invariant or
      semiinvariant autoreactive receptors. Finally, we demonstrate that the MHC
      restricted TCR repertoire is essentially non-cross-reactive to CD1d. Altogether,
      these findings imply that lipid recognition by CD1d-restricted T cells may have
      largely evolved as an innate rather than an adaptive arm of the mouse immune
      system.

PMID- 11304552
TI  - Telomere shortening accompanies increased cell cycle activity during serial
      transplantation of hematopoietic stem cells.
AB  - Reactivation of telomerase and maintenance of telomere length can lead to the
      prevention of replicative senescence in some human somatic cells grown in vitro.
      To investigate whether telomere shortening might also play a role in the
      limitation of hematopoietic stem cell (HSC) division capacity in vivo, we
      analyzed telomere length during serial transplantation of murine HSCs. Southern
      blot analysis of telomere length in donor bone marrow cells revealed extensive
      shortening ( approximately 7 kb) after just two rounds of HSC transplantation.
      The number of cycling HSCs increased after transplantation and remained elevated
      for at least 4 mo, while the frequency of HSCs in the bone marrow was completely
      regenerated by 2 mo after transplantation. Direct analysis of telomeres in HSCs
      by fluorescent in situ hybridization during serial transplantation also revealed
      a reduction in telomere size. Together, these data show that telomeres shorten
      during division of HSCs in vivo, and are consistent with the hypothesis that
      telomere shortening may limit the replicative capacity of HSCs.

PMID- 11304551
TI  - Perivascular macrophages are the primary cell type productively infected by
      simian immunodeficiency virus in the brains of macaques: implications for the
      neuropathogenesis of AIDS.
AB  - The macrophage is well established as a target of HIV and simian immunodeficiency
      virus (SIV) infection and a major contributor to the neuropathogenesis of AIDS.
      However, the identification of distinct subpopulations of monocyte/macrophages
      that carry virus to the brain and that sustain infection within the central
      nervous system (CNS) has not been examined. We demonstrate that the perivascular
      macrophage and not the parenchymal microglia is the primary cell productively
      infected by SIV. We further demonstrate that although productive viral infection
      of the CNS occurs early, thereafter it is not easily detectable until terminal
      AIDS. The biology of perivascular macrophages, including their rate of turnover
      and replacement by peripheral blood monocytes, may explain the timing of
      neuroinvasion, disappearance, and reappearance of virus in the CNS, and questions
      the ability of the brain to function as a reservoir for productive infection by
      HIV/SIV.

PMID- 11304553
TI  - Absence of mitochondrial superoxide dismutase results in a murine hemolytic
      anemia responsive to therapy with a catalytic antioxidant.
AB  - Manganese superoxide dismutase 2 (SOD2) is a critical component of the
      mitochondrial pathway for detoxification of O2(-), and targeted disruption of
      this locus leads to embryonic or neonatal lethality in mice. To follow the
      effects of SOD2 deficiency in cells over a longer time course, we created
      hematopoietic chimeras in which all blood cells are derived from fetal liver stem
      cells of Sod2 knockout, heterozygous, or wild-type littermates. Stem cells of
      each genotype efficiently rescued hematopoiesis and allowed long-term survival of
      lethally irradiated host animals. Peripheral blood analysis of leukocyte
      populations revealed no differences in reconstitution kinetics of T cells, B
      cells, or myeloid cells when comparing Sod2(+/+), Sod2(-/-), and Sod2(+/-) fetal
      liver recipients. However, animals receiving Sod2(-/-) cells were persistently
      anemic, with findings suggestive of a hemolytic process. Loss of SOD2 in
      erythroid progenitor cells results in enhanced protein oxidative damage, altered
      membrane deformation, and reduced survival of red cells. Treatment of anemic
      animals with Euk-8, a catalytic antioxidant with both SOD and catalase
      activities, significantly corrected this oxidative stress-induced condition. Such
      therapy may prove useful in treatment of human disorders such as sideroblastic
      anemia, which SOD2 deficiency most closely resembles.

PMID- 11304554
TI  - Identification of a chlamydial protease-like activity factor responsible for the
      degradation of host transcription factors.
AB  - Microbial pathogens have been selected for the capacity to evade or manipulate
      host responses in order to survive after infection. Chlamydia, an obligate
      intracellular pathogen and the causative agent for many human diseases, can
      escape T lymphocyte immune recognition by degrading host transcription factors
      required for major histocompatibility complex (MHC) antigen expression. We have
      now identified a chlamydial protease- or proteasome-like activity factor (CPAF)
      that is secreted into the host cell cytosol and that is both necessary and
      sufficient for the degradation of host transcription factors RFX5 and upstream
      stimulation factor 1 (USF-1). The CPAF gene is highly conserved among chlamydial
      strains, but has no significant overall homology with other known genes. Thus,
      CPAF represents a unique secreted protein produced by an obligate intracellular
      bacterial pathogen to interfere with effective host adaptive immunity.

PMID- 11304555
TI  - Differential signaling and tumor necrosis factor receptor-associated factor
      (TRAF) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent
      membrane protein 1 (LMP1).
AB  - Latent membrane protein 1 (LMP1) plays a critical role in B cell transformation
      by Epstein-Barr virus (EBV) and appears to mimic a constitutively active CD40
      receptor. Intracellular tumor necrosis factor (TNF) receptor-associated factor
      (TRAF) adapter proteins, shown to contribute to signaling by both CD40 and LMP1,
      were recruited by both molecules to lipid-enriched membrane rafts. However, we
      found that TRAFs 2 and 3 were subsequently degraded after CD40- but not LMP1
      induced signaling. This degradation was proteasome-dependent and required direct
      TRAF binding by CD40. Using a model system designed to directly compare the
      signaling potency of the cytoplasmic domains of LMP1 and CD40 in B lymphocytes,
      we found that LMP1 more potently activates c-Jun kinase and nuclear factor kappaB
      and induces higher levels of several B cell effector functions than does CD40.
      This suggests that LMP1 utilizes a modified CD40 signaling pathway. Failure to
      regulate TRAFs may contribute to the enhanced capacity of LMP1 to activate B
      cells as well as promote B cell transformation.

PMID- 11304557
TI  - The clinical course of experimental autoimmune encephalomyelitis and inflammation
      is controlled by the expression of CD40 within the central nervous system.
AB  - Although it is clear that the function of CD40 on peripheral hematopoietic cells
      is pivotal to the development of autoimmunity, the function of CD40 in autoimmune
      disease outside this compartment is unresolved. In a model of experimental
      autoimmune encephalomyelitis (EAE), evidence is presented that CD40-CD154
      interactions within the central nervous system (CNS) are critical determinants of
      disease development and progression. Using bone marrow (BM) chimeric mice, the
      data suggest that the lack of expression of CD40 by CNS-resident cells diminishes
      the intensity and duration of myelin oligodendrocyte glycoprotein (MOG)-induced
      EAE and also reduces the degree of inflammatory cell infiltrates into the CNS.
      Although CNS inflammation is compromised in the CD40(+/+)-->CD40(-/-) BM chimeric
      mice, the restricted CD40 expression had no impact on peripheral T cell priming
      or recall responses. Analysis of RNA expression levels within the CNS
      demonstrated that encephalitogenic T cells, which entered a CNS environment in
      which CD40 was absent from parenchymal microglia, could not elicit the expression
      of chemokines within the CNS. These data provide evidence that CD40 functions
      outside of the systemic immune compartment to amplify organ-specific
      autoimmunity.

PMID- 11304556
TI  - PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation factor
      (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of macrophages.
AB  - The Fcgamma receptor (FcgammaR)-mediated phagocytosis of macrophages is a complex
      process where remodeling of both the actin-based cytoskeleton and plasma membrane
      occur coordinately. Several different families of small GTPases are involved. We
      have isolated a GTPase-activating protein (GAP) for ADP-ribosylation factor
      (ARF), paxillin-associated protein with ARFGAP activity (PAG)3/Papalpha/KIAA0400,
      from mature monocytes and macrophage-like cells. Mammalian ARFs fall into three
      classes, and the class III isoform (ARF6) has been shown to be involved in
      FcgammaR-mediated phagocytosis. Here we report that PAG3 is enriched together
      with ARF6 and F-actin at phagocytic cups formed beneath immunoglobulin G
      opsonized beads in P388D1 macrophages, in which overexpression of ARF6, but not
      ARF1 (class I) or ARF5 (class II), inhibits the phagocytosis. Overexpression of
      PAG3, but not its GAP-inactive mutant, attenuated the focal accumulation of F
      actin and blocked phagocytosis, although surface levels of the FcgammaRs were not
      affected. Other ubiquitously expressed ARFGAPs, G protein-coupled receptor kinase
      interactors GIT2 and GIT2-short/KIAA0148, which we have shown to exhibit GAP
      activity for ARF1 in COS-7 cells, did not accumulate at the phagocytic cups or
      inhibit phagocytosis. Moreover, cooverexpression of ARF6, but not ARF1 or ARF5,
      restored the phagocytic activity of PAG3-overexpressing cells. We propose that
      PAG3 acts as a GAP for ARF6 and is hence involved in FcgammaR-mediated
      phagocytosis in mouse macrophages.

PMID- 11304558
TI  - Donor-derived IP-10 initiates development of acute allograft rejection.
AB  - An allograft is often considered an immunologically inert playing field on which
      host leukocytes assemble and wreak havoc. However, we demonstrate that graft
      specific physiologic responses to early injury initiate and promulgate
      destruction of vascularized grafts. Serial analysis of allografts showed that
      intragraft expression of the three chemokine ligands for the CXC chemo-kine
      receptor CXCR3 was induced in the order of interferon (IFN)-gamma-inducible
      protein of 10 kD (IP-10, or CXCL10), IFN-inducible T cell alpha-chemoattractant
      (I-TAC; CXCL11), and then monokine induced by IFN-gamma (Mig, CXCL9). Initial IP
      10 production was localized to endothelial cells, and only IP-10 was induced by
      isografting. Anti-IP-10 monoclonal antibodies prolonged allograft survival, but
      surprisingly, IP-10-deficient (IP-10(-/-)) mice acutely rejected allografts.
      However, though allografts from IP-10(+/+) mice were rejected by day 7, hearts
      from IP-10(-/-) mice survived long term. Compared with IP-10(+/+) donors, use of
      IP-10(-/-) donors reduced intragraft expression of cytokines, chemokines and
      their receptors, and associated leukocyte infiltration and graft injury. Hence,
      tissue-specific generation of a single chemokine in response to initial
      ischemia/reperfusion can initiate progressive graft infiltration and
      amplification of multiple effector pathways, and targeting of this proximal
      chemokine can prevent acute rejection. These data emphasize the pivotal role of
      donor-derived IP-10 in initiating alloresponses, with implications for tissue
      engineering to decrease immunogenicity, and demonstrate that chemokine redundancy
      may not be operative in vivo.

PMID- 11304559
TI  - Protection from respiratory virus infections can be mediated by antigen-specific
      CD4(+) T cells that persist in the lungs.
AB  - Although CD4(+) T cells have been shown to mediate protective cellular immunity
      against respiratory virus infections, the underlying mechanisms are poorly
      understood. For example, although phenotypically distinct populations of memory
      CD4(+) T cells have been identified in different secondary lymphoid tissues, it
      is not known which subpopulations mediate protective cellular immunity. In this
      report, we demonstrate that virus-specific CD4(+) T cells persist in the lung
      tissues and airways for several months after Sendai virus infection of C57BL/6
      mice. A large proportion of these cells possess a highly activated phenotype
      (CD44(hi), CD62L(lo), CD43(hi), and CD25(hi)) and express immediate effector
      function as indicated by the production of interferon gamma after a 5-h
      restimulation in vitro. Furthermore, intratracheal adoptive transfer of lung
      memory cells into beta2m-deficient mice demonstrated that lung-resident virus
      specific CD4(+) T cells mediated a substantial degree of protection against
      secondary virus infection. Taken together, these data demonstrate that activated
      memory CD4(+) T cells persisting at mucosal sites play a critical role in
      mediating protective cellular immunity.

PMID- 11304562
TI  - Epstein-Barr virus associated polymorphic lymphoproliferative disorders occurring
      in nontransplant settings.

PMID- 11304560
TI  - Migration and function of antigen-primed nonpolarized T lymphocytes in vivo.
AB  - Upon antigenic stimulation, naive T lymphocytes proliferate and a fraction of the
      activated cells acquire a T helper cell type 1 (Th1) or Th2 phenotype as well as
      the capacity to migrate to inflamed tissues. However, the antigen-primed T cells
      that receive a short T cell receptor (TCR) stimulation do not acquire effector
      function and remain in a nonpolarized state. Using TCR transgenic CD4(+) T cells
      in an adoptive transfer system, we compared the in vivo migratory capacities of
      naive, nonpolarized, Th1 or Th2 cells. Although all cell types migrated to the
      spleen, only naive and nonpolarized T cells efficiently migrated to lymph nodes.
      In addition Th1, but not Th2, migrated to inflamed tissues. In the lymph nodes,
      nonpolarized T cells proliferated and acquired effector function in response to
      antigenic stimulation, displaying lower activation threshold and faster kinetics
      compared with naive T cells. These results suggest that nonpolarized T cells are
      in an intermediate state of differentiation characterized by lymph node homing
      capacity and increased responsiveness that allows them to mount a prompt and
      effective secondary response.

PMID- 11304563
TI  - In vitro models of vasculogenesis and angiogenesis.

PMID- 11304564
TI  - Engineering and characterization of functional human microvessels in
      immunodeficient mice.
AB  - SUMMARY: Current model systems used to investigate angiogenesis in vivo rely on
      the interpretation of results obtained with nonhuman endothelial cells. Recent
      advances in tissue engineering and molecular biology suggest the possibility of
      engineering human microvessels in vivo. Here we show that human dermal
      microvascular endothelial cells (HDMEC) transplanted into severe combined
      immunodeficient (SCID) mice on biodegradable polymer matrices differentiate into
      functional human microvessels that anastomose with the mouse vasculature. HDMEC
      were stably transduced with Flag epitope or alkaline phosphatase to confirm the
      human origin of the microvessels. Endothelial cells appeared dispersed throughout
      the sponge 1 day after transplantation, became organized into empty tubular
      structures by Day 5, and differentiated into functional microvessels within 7 to
      10 days. Human microvessels in SCID mice expressed the physiological markers of
      angiogenesis: CD31, CD34, vascular cellular adhesion molecule 1 (VCAM-1), and
      intercellular adhesion molecule 1 (ICAM-1). Human endothelial cells became
      invested by perivascular smooth muscle alpha-actin-expressing mouse cells 21 days
      after implantation. This model was used previously to demonstrate that
      overexpression of the antiapoptotic protein Bcl-2 in HDMEC enhances
      neovascularization, and that apoptotic disruption of tumor microvessels is
      associated with apoptosis of surrounding tumor cells. The proposed SCID mouse
      model of human angiogenesis is ideally suited for the study of the physiology of
      microvessel development, pathologic neovascular responses such as tumor
      angiogenesis, and for the development and investigation of strategies designed to
      enhance the neovascularization of engineered human tissues and organs.

PMID- 11304565
TI  - Differential expression of cdc25 cell-cycle-activating phosphatases in human
      colorectal carcinoma.
AB  - cdc25 is a family of cell-cycle phosphatases that activate the cyclin-dependent
      kinases. cdc25A and B, but not C, have oncogenic potential in vitro. In this
      study, we analyzed the possible implication of cdc25 genes in the progression of
      colorectal tumors. RNA and DNA were extracted from 34 paired tumor and normal
      colorectal tissues and examined by Northern blot, RT-PCR, and Southern blot,
      respectively. Protein expression was analyzed by Western blot in a subset of
      normal and tumor samples. The expression levels were correlated with the
      clinicopathologic characteristics and survival of the patients. cdc25B mRNA was
      overexpressed in 19 carcinomas (56%). A significant correlation was observed
      between high cdc25B mRNA levels and the relapse-free, overall, and cancer-related
      survival of the patients. The cdc25B2 splicing variant was detected in 27
      carcinomas (79%) but only in 9 normal samples (26%) and was associated with the
      grade of the differentiation of the tumors. cdc25A mRNA was overexpressed in four
      tumors (12%) and cdc25C1 mRNA was overexpressed in nine tumors (26%). A new
      cdc25C2 splicing variant lacking exon 4 and 5 was identified in all of the tumors
      and in 56% of the normal samples. No amplifications or gene rearrangements of
      these genes were detected. In conclusion, these findings indicate that cdc25
      isoforms and splicing variants are differentially regulated in colorectal
      carcinomas and may participate in the development of these tumors. Additionally,
      the correlation between cdc25B mRNA levels and the survival of the patients also
      suggest that the cdc25B isoform may be involved in the progression of the
      disease.

PMID- 11304566
TI  - Small marker chromosome identification in metaphase and interphase using
      centromeric multiplex fish (CM-FISH).
AB  - Multicolor karyotyping procedures, such as multiplex fluorescence in situ
      hybridization (M-FISH), spectral karyotyping, or color-changing karyotyping, can
      be used to detect chromosomal rearrangements and marker chromosomes in prenatal
      diagnosis, peripheral blood cultures, leukemia, and solid tumors, especially in
      cases where G-banding is not sufficient. A regular M-FISH analysis requires
      relatively large amounts of labeled DNA (microgram quantities), is not
      informative in interphase nuclei, hybridization can take up to 2 to 3 days, and
      unlabeled human chromosome-painting probes are not available commercially. Unique
      probes (plasmids, PAC), specific for centromeric or subtelomeric chromosomal
      regions, can replace the painting probes in M-FISH to address specific issues,
      such as the identification of marker chromosomes and aneuploidies. A set of
      plasmid probes carrying repetitive sequences specific for the alpha-satellite
      region of all human chromosomes were combined in a metaphase assay and an
      interphase assay, allowing identification of aneuploidies in one hybridization
      step, on a single cytogenetic slide. The fluorophore-dUTP and the labeled
      antibodies required to label and detect the DNA probes can be prepared in any
      laboratory. All DNA probes can be easily isolated and labeled using common
      molecular cytogenetic procedures. Because of the repetitive nature of the probes,
      hybridization time is short, usually less than 1 hour, and the analysis can be
      performed with nonspecialized image-processing software.

PMID- 11304567
TI  - Cryptic translocation identification in human and mouse using several telomeric
      multiplex fish (TM-FISH) strategies.
AB  - Experimental data published in recent years showed that up to 10% of all cases of
      mild to severe idiopathic mental retardation may result from small rearrangements
      of the subtelomeric regions of human chromosomes. To detect such cryptic
      translocations, we developed a "telomeric" multiplex fluorescence in situ
      hybridization (M-FISH) assay, using a set of previously published and
      commercially available subtelomeric probes. This set of probes includes 41
      cosmid/PAC/P1 clones located from less than 100 kilobases to approximately 1
      megabase from the end of the chromosomes. Similarly, a published mouse probe set,
      comprised of BACs hybridizing to the closest known marker toward the centromere
      and telomere of each mouse chromosome, was used to develop a mouse-specific
      "telomeric" M-FISH. Three different combinatorial labeling strategies were used
      to simultaneously detect all human subtelomeric regions on one slide. The
      simplest approach uses only three fluors and can be performed in laboratories
      lacking sophisticated imaging equipment or personnel highly trained in
      cytogenetics. A standard fluorescence microscope equipped with only three filters
      is sufficient. Fluor-dUTPs and labeled probes can be custom made, thus
      dramatically reducing costs. Images can be prepared using imaging software (Adobe
      Photoshop) and analysis performed by simple visual inspection.

PMID- 11304568
TI  - Transmission of mouse senile amyloidosis.
AB  - SUMMARY: In mouse senile amyloidosis, apolipoprotein A-II polymerizes into
      amyloid fibrils (AApoAII) and deposits systemically. Peripheral injection of
      AApoAII fibrils into young mice induces systemic amyloidosis (Higuchi et al,
      1998). We isolated AApoAII amyloid fibrils from the livers of old R1.P1-Apoa2(c)
      mice and injected them with feeding needles into the stomachs of young R1.P1
      Apoa2(c) mice for 5 consecutive days. After 2 months, all mice had AApoAII
      deposits in the lamina propria of the small intestine. Amyloid deposition
      extended to the tongue, stomach, heart, and liver at 3 and 4 months after
      feeding. AApoAII suspended in drinking water also induced amyloidosis. Amyloid
      deposition was induced in young mice reared in the same cage for 3 months with
      old mice who had severe amyloidosis. Detection of AApoAII in feces of old mice
      and induction of amyloidosis by the injection of an amyloid fraction of feces
      suggested the propagation of amyloidosis by eating feces. Here, we substantiate
      the transmissibility of AApoAII amyloidosis and present a possible pathogenesis
      of amyloidosis, ie, oral transmission of amyloid fibril conformation, where we
      assert that exogenous amyloid fibrils act as templates and change the
      conformation of endogenous amyloid protein to polymerize into amyloid fibrils.

PMID- 11304569
TI  - Method for procuring specific populations of viable human prostate cells for
      research.
AB  - SUMMARY: A wider range of research can be conducted on viable tissue samples than
      on fixed or frozen samples. A major obstacle to studying viable prostate tissue
      samples is the inability to accurately identify cancer on direct examination of
      unembedded tissue. We used a dissecting microscope to identify cancer in unfixed
      prostate tissue samples stained on the cut surface with 0.5% aqueous toluidine
      blue. We measured the diagnostic accuracy of this technique in 25 consecutive
      prostatectomies, determined the viability of procured samples, and estimated the
      effect on final pathologic assessment. Both surfaces of a 3- to 5-mm thick cross
      section taken midway between base and apex of the prostate were examined. A 4-mm
      punch biopsy was directed to one benign and one malignant area when clearly
      present. The dissecting microscope allowed clearcut recognition of carcinoma in
      17 of the 25 cross-sections, and carcinoma was confirmed in all 17 (100%). In 8
      of 25 cases, no procurement was attempted because no carcinoma was evident in the
      one cross-section studied. Twenty of 25 cross-sections were adequate for benign
      tissue procurement; five of the cross-sections were not suitable for procurement
      because of the presence of extensive carcinoma or atrophy. Seventeen of the 20
      were accurately diagnosed as benign (85%); one showed pseudohyperplastic
      adenocarcinoma, one showed focal high-grade prostatic intraepithelial neoplasia,
      and one showed urothelial carcinoma in situ. Prostatic epithelium obtained with
      the technique remains viable and can be separated from stroma. The dissecting
      microscope technique appears to facilitate rather than interfere with accurate
      pathologic assessment: extraprostatic extension or positive margins were
      correctly identified during tissue procurement in three cases. The procedure
      takes only about 30 minutes.

PMID- 11304570
TI  - Syndecan-4 deficiency increases susceptibility to kappa-carrageenan-induced renal
      damage.
AB  - SUMMARY: The expression and roles of syndecan-4 in the kidney were investigated.
      Syndecan-4 expression was detected in the ureteric bud invaginating into the
      metanephric mesenchyme at 11.5 gestational days, and remained in the collecting
      ducts, distal renal tubules, glomeruli, and some capillaries between renal
      tubules until the mature kidney stage. However, organogenesis of the kidney was
      normal in syndecan-4-deficient (Synd4[-/-]) mice. Although most renal functions
      of Synd4(-/-) mice were not impaired, a significant increase in susceptibility to
      kappa-carrageenan-induced renal damage was observed in these mice. kappa
      Carrageenan was heavily deposited in the collecting ducts of Synd4(-/-) mice and
      caused obstructive nephropathy, leading to death of 7 of 24 Synd4(-/-) mice
      within 7 days after administration, whereas none of 24 Synd4(+/+) mice died.
      After administration of kappa-carrageenan, blood urea nitrogen of Synd4(-/-) mice
      was significantly higher than that of Synd4(+/+) mice. Thus, syndecan-4 may
      function to prevent kappa-carrageenan deposition in the collecting ducts.

PMID- 11304571
TI  - Comparison of serous and mucinous ovarian carcinomas: distinct pattern of allelic
      loss at distal 8p and expression of transcription factor GATA-4.
AB  - Using comparative genomic hybridization (CGH), we have previously demonstrated
      frequent loss of 8p, especially its distal part, in ovarian carcinoma. To compare
      the deletion map of distal 8p in serous and mucinous ovarian carcinomas, we
      performed allelic analysis with 18 polymorphic microsatellite markers at 8p21
      p23. In serous carcinoma, loss of heterozygosity (LOH) was detected in 67% of the
      samples, and the majority of the carcinomas showed loss of all or most of the
      informative markers. In contrast, only 21% of mucinous carcinomas showed allelic
      loss, with only one or two loci showing LOH in each sample. In serous carcinomas,
      LOH was associated with higher grade tumors. Three distinct minimal common
      regions of loss could be defined in serous carcinomas (at 8p21.1, 8p22-p23.1, and
      8p23.1). Expression of a transcription factor gene, GATA4, located at one of
      these regions (8p23.1) was studied in serous and mucinous ovarian carcinomas by
      Northern blotting and immunohistochemical staining of tumor microarray.
      Expression was found to be lost in most serous carcinomas but retained in the
      majority of mucinous carcinomas. Our results suggest distinct pathogenetic
      pathways in serous and mucinous ovarian carcinomas and the presence of more than
      one tumor suppressor gene at 8p involved in the tumorigenesis of serous
      carcinoma.

PMID- 11304572
TI  - Accumulation of allelic changes at chromosomes 7p, 18q, and 2 in parathyroid
      lesions of uremic patients.
AB  - We examined by microsatellite allelotyping 69 hyperplastic lesions of the
      parathyroid glands from 23 patients with refractory, uremic hyperparathyroidism.
      Allelic changes, at least at one chromosomal arm, were found in 31 of the 69
      lesions (43%). Alteration at a single chromosome was seen in 14 lesions and at
      two to four chromosomes in 11 lesions, and there were five to eight alterations
      in 5 nodules. Allelic imbalance occurred most frequently at chromosome 7p between
      the EGFR gene and locus D7S817 (16%), at 18q between loci D18S61 and D18S70
      (14%), and at chromosome 2 between D2S380 and D2S1391 (9%). X-inactivation study
      showed a monoclonal growth in 18 of 29 nodules in females, and a loss of the Y
      chromosome was seen in 8 of the 39 nodules obtained from males. Our results
      suggest that the uremic "hyperplastic" nodules have a molecular pathway distinct
      from those known for sporadic primary parathyroid adenomas.

PMID- 11304573
TI  - Microsatellite Instability and hMLH1 and hMSH2 expression analysis in familial
      and sporadic colorectal cancer.
AB  - Immunohistochemical expression analysis of mismatch repair gene products has been
      suggested for the prediction of hereditary nonpolyposis colorectal cancer (HNPCC)
      carrier status in cancer families and the selection of microsatellite instability
      (MSI)-positive tumors in sporadic colorectal cancer. In this study, we aimed to
      evaluate hMSH2 and hMLH1 immunohistochemistry in familial and sporadic colorectal
      cancer. We found that immunohistochemistry allowed us to identify patients with
      germline mutations in hMSH2 and many cases with germline mutations in hMLH1.
      However, some missense and truncating mutations may be missed. In addition, hMLH1
      promoter methylation, commonly occurring in familial and sporadic MSI-positive
      colorectal cancer, can complicate the interpretation of immunohistochemical
      expression analyses. Our results suggest that immunohistochemistry cannot replace
      testing for MSI to predict HNPCC carrier status or identify MSI-positive sporadic
      colorectal cancer.

PMID- 11304574
TI  - Myeloperoxidase-dependent generation of hypochlorite-modified proteins in human
      placental tissues during normal pregnancy.
AB  - Myeloperoxidase (MPO), which is released from cytoplasmic granules of activated
      phagocytes by a degranulation process, reacts with H(2)O(2) (generated during the
      oxidative burst) and chloride ions to generate hypochlorous acid/hypochlorite
      (HOCl/OCl(-)). HOCl, a strong oxidant, in turn reacts with proteins to form HOCl
      modified proteins. The presence of these cytotoxic chloramines during
      inflammatory conditions, eg, atherosclerosis and glomerular and
      tubulointerstitial injury, suggested that chloramines are powerful oxidants that
      can have profound biologic effects. In the present study, immunoreactive MPO was
      identified in fetal membranes and the basal plate and in maternal and fetal blood
      cells of human placental tissues. Monocytes/macrophages represent the major cell
      source for MPO in human placental tissues. Immunohistochemical findings revealed
      that HOCl-modified proteins are present in normal human term placenta but not
      during the first trimester of pregnancy (Weeks 7 to 12). HOCl-modified proteins
      were localized in areas formed by fetally derived cells as well as maternal
      decidual tissues, ie, areas where fetal extravillous trophoblast cells invade the
      maternal tissue and stimulate the maternal immune system. HOCl-modified proteins,
      products of the MPO-H(2)O(2)-chloride system in vivo, were not present
      intracellularly, but immunoreactivity for HOCl-modified proteins was cell
      associated and/or present in the extracellular matrix. Extravillous trophoblast
      cells, which may also exert phagocytic activities, showed no intracellular
      immunoreactivity for MPO or HOCl-modified proteins. The present findings indicate
      that the generation of HOCl-modified proteins during normal pregnancy is a
      physiologic rather than a pathophysiologic process.

PMID- 11304575
TI  - TCL1 oncogene expression in B cell subsets from lymphoid hyperplasia and distinct
      classes of B cell lymphoma.
AB  - Activation of the TCL1 oncogene has been implicated in T cell leukemias/lymphomas
      and recently was associated with AIDS diffuse large B cell lymphomas (AIDS
      DLBCL). Also, in nonmalignant lymphoid tissues, antibody staining has shown that
      mantle zone B cells expressed abundant Tcl1 protein, whereas germinal center (GC;
      centrocytes and centroblasts) B cells showed markedly reduced expression. Here,
      we analyze isolated B cell subsets from hyperplastic tonsil to determine a more
      precise pattern of Tcl1 expression with development. We also examine multiple B
      cell lines and B lymphoma patient samples to determine whether different tumor
      classes retain or alter the developmental pattern of expression. We show that
      TCL1 expression is not affected by Epstein-Barr virus (EBV) infection and is high
      in naive B cells, reduced in GC B cells, and absent in memory B cells and plasma
      cells. Human herpesvirus-8 infected primary effusion lymphomas (PEL) and multiple
      myelomas are uniformly TCL1 negative, whereas all other transformed B cell lines
      tested express moderate to abundant TCL1. This observation supports the
      hypothesis that PEL, like myeloma, usually arise from post-GC stages of B cell
      development. Tcl1 protein is also detected in most naive/GC-derived B lymphoma
      patient samples (23 of 27 [85%] positive), whereas most post-GC-derived B
      lymphomas lack expression (10 of 41 [24%] positive). These data indicate that the
      pattern of Tcl1 expression is distinct between naive/GC and post-GC-derived B
      lymphomas (P < 0.001) and that the developmental pattern of expression is largely
      retained. However, post-GC-derived AIDS-DLBCL express TCL1 at a frequency
      equivalent to naive/GC-derived B lymphomas in immune-competent individuals (7 of
      9 [78%] positive), suggesting that TCL1 down-regulation is adversely affected by
      severe immune system dysfunction. These findings demonstrate that TCL1 expression
      in B cell lymphoma usually reflects the stage of B cell development from which
      they derive, except in AIDS-related lymphomas.

PMID- 11304576
TI  - Amplification of growth regulatory genes in intraductal breast cancer is
      associated with higher nuclear grade but not with the progression to
      invasiveness.
AB  - Ductal carcinoma in situ (DCIS), as an identifiable progenitor lesion of invasive
      breast cancer, represents a morphologically, biologically, and prognostically
      heterogeneous disease. It is not clear which molecular mechanisms are involved in
      progression to infiltrative growth. In this study, 83 DCIS classified according
      to the Van Nuys grading scheme were examined for amplification of growth
      regulatory genes that have been found to be amplified in invasive breast cancer
      (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1 genes). Exact quantification
      of gene amplification was enabled by a combination of laser microdissection of
      paraffin-embedded tissue with real-time PCR. In DCIS, gene amplifications of all
      tested genes were found. The most frequently amplified gene was c-erbB2 found in
      21 of 83 (25%) cases. Amplification of the other genes under investigation was
      observed in 4% to 6% of cases, high-grade DCIS being predominantly affected. High
      grade DCIS differed significantly from low- and intermediate-grade DCIS in
      frequency and level of c-erbB2 amplification. In addition, high-grade DCIS
      revealed an accumulation of genetic aberrations. Amplification status in pure in
      situ lesions did not differ from intraductal carcinoma with an infiltrative
      component, indicating that although associated with a higher nuclear grade gene
      amplification might not represent an independent prognostic marker of disease
      progression.

PMID- 11304577
TI  - Methylation in the p53 promoter is a supplementary route to breast
      carcinogenesis: correlation between CpG methylation in the p53 promoter and the
      mutation of the p53 gene in the progression from ductal carcinoma in situ to
      invasive ductal carcinoma.
AB  - Aberrant methylation in the CpG sites located in the promoter region of several
      tumor suppressor genes has been reported in various types of cancers. However,
      the methylation status of the p53 promoter has not been clearly determined and no
      information is available on its role in breast cancer. The aim of the study was
      to determine the presence and timing of the methylation of CpG sites in the p53
      promoter, in the progression from ductal carcinoma in situ to invasive cancer. We
      also explored the correlation between the CpG methylation of the p53 promoter and
      p53 mutation during the progression of breast cancer. The corresponding lesions
      of both the invasive and noninvasive types were microdissected in paraffin
      embedded tissue of 26 breast carcinomas. Bisulfite-modified DNA sequencing for
      methylation status in the p53 promoter was carried out, and double-strand DNA
      sequencing was performed in the promoter region and exons 4 to 9 of the p53 gene.
      CpG site methylation in the p53 promoter was detected in three cases (11.5%). Two
      noninvasive and three invasive lesions harbored CpG methylation in the p53
      promoter. Methylations in more than one site were observed in three lesions, all
      of which contained methylation in two sites. The methylated CpG sites were
      located near the AP1 and YY-1 binding sites and at the YY-1 binding site. The p53
      mutation was not found in the lesions where methylation in p53 promoter region
      was evident. In 16 cases (61.5%), neither methylation nor p53 mutation was
      detected. We conclude that the methylation in the p53 promoter region is found in
      the breast cancer irrespective of the status of invasion, and that the
      hypermethylation in the p53 promoter region is an alternative pathway to
      tumorigenesis where there is no p53 gene mutation.

PMID- 11304578
TI  - Room temperature activates human blood platelets.
AB  - Temperatures ranging from room temperature (20 degrees C) to 42 degrees C are
      generally not considered to have an activating effect on platelets. However, this
      assumption is not supported by clinical phenomena that result in hemostatic
      failure related to hypothermia. In this study, we investigated the effect of
      temperatures between room temperature (20 degrees C) and 42 degrees C on human
      blood platelets and found that room temperature causes marked activation of
      platelets. Major changes in platelet morphology were seen at 20 degrees C
      compared to resting platelets at 37 degrees C. Platelet morphology was
      investigated with noninvasive live cell techniques (light microscopy and dynamic
      and static light scattering), as well as with transmission and scanning electron
      microscopy. The changes in platelet morphology correlated with the expression of
      the activation marker, activated glycoprotein (GP) IIb-IIIa, measured by flow
      cytometry. Twenty-five percent to 30% of platelets expressed activated GPIIb-IIIa
      after exposure to 20 degrees C for 10 minutes. In the presence of serotonin re
      uptake inhibitors, the serotonin content of platelets at 20 degrees C was twice
      that of resting platelets. In comparison, moderate heat shock conditions (42
      degrees C for 10 minutes) caused no signs of platelet activation as indicated by
      the absence of morphological alterations, no expression of activated GPIIb-IIIa,
      and no changes in serotonin content. These results show that room temperature by
      itself significantly activates platelets and has an effect on the platelet
      serotonin content. This may contribute to both the functional lesion associated
      with 22 degrees C storage of platelets for transfusion and the in vivo hemostatic
      failure after hypothermia.

PMID- 11304579
TI  - Molecular characterization of undifferentiated-type gastric carcinoma.
AB  - As the great majority of gastric cancers develop histologically differentiated,
      and a significant proportion of differentiated-type carcinomas progress to become
      undifferentiated, both histological types are likely to share several common
      genetic abnormalities, such as p53 mutations at advanced stages. However, a
      subset of gastric cancers develop as undifferentiated carcinomas, including
      signet-ring cell carcinoma and poorly differentiated adenocarcinoma, and the
      molecular pathogenesis of this tumor type remains largely unknown. To
      characterize the molecular features of undifferentiated-type gastric carcinomas
      that developed as undifferentiated-type, we examined for p53, APC, and epithelial
      (E)-cadherin gene mutations, microsatellite alterations including loss of
      heterozygosity (LOH) and microsatellite instability (MSI), and hypermethylation
      of the E-cadherin gene promoter in 26 early undifferentiated gastric carcinomas,
      consisting of 14 signet-ring cell carcinomas and 12 poorly differentiated
      adenocarcinomas. E-cadherin expression was evaluated immunohistochemically. p53
      mutations were detected in only one poorly differentiated adenocarcinoma sample
      (3.8%; 1/26), whereas no APC or E-cadherin mutations were found. LOH was present
      only at D8S261 on the short arm of chromosome 8 in 2 of 14 (14%) informative
      tumors, both of which were poorly differentiated adenocarcinomas, and MSI was not
      observed in any of the tumors. No signet-ring cell carcinomas have been found to
      carry gene mutations or microsatellite alterations. In contrast, hypermethylation
      of the E-cadherin promoter occurred in 69% (18/26) of the tumors; 57% (8/14) of
      signet-ring cell carcinomas, and 83% (10/12) of poorly differentiated
      adenocarcinomas, and was significantly associated with loss or reduced expression
      of E-cadherin. Thus, whereas tumor suppressor gene mutation, LOH, and MSI were
      less common in undifferentiated-type early gastric carcinomas, epigenetic
      inactivation of E-cadherin via promoter hypermethylation may be an early critical
      event in the development of undifferentiated tumors.

PMID- 11304580
TI  - S100A2, a putative tumor suppressor gene, regulates in vitro squamous cell
      carcinoma migration.
AB  - It has been previously shown that S100A2 is down-regulated in tumor cells and can
      be considered a tumor suppressor. We have recently shown that this down
      regulation can be observed particularly in epithelial tissue, where S100A2
      expression decreases remarkably in tumors as compared with normal specimens. In
      the present paper we investigate whether S100A2 could play a tumor-suppressor
      role in certain epithelial tissues by acting at the cell migration level. To this
      end, we made use of five in vitro human head and neck squamous cell carcinoma
      lines in which we characterized S100A2 expression at both RNA and protein level.
      To characterize the influence of S100A2 on cell kinetic and cell motility
      features, we used two complementary approaches involving specific antisense
      oligonucleotides and the addition of S100A2 to the culture media. The different
      expression analyses gave a coherent demonstration of the fact that the FADU and
      the RPMI-2650 cell lines exhibit high and low levels of S100A2 expression,
      respectively. Antisense oligonucleotides (in FADU) and extracellular treatments
      (in RPMI) showed that, for these two models, S100A2 had a clear inhibitory
      influence on cell motility while modifying the cell kinetic parameters only
      slightly. These effects seem to be related, at least in part, to a modification
      in the polymerization/depolymerization dynamics of the actin microfilamentary
      cytoskeleton. Furthermore, we found evidence of the presence of the receptor for
      advanced glycation end-products (RAGE) in RPMI cells, which may act as a receptor
      for extracellular S100A2. The present study therefore presents experimentally
      based evidence showing that S100A2 could play a tumor-suppressor role in certain
      epithelial tissues by restraining cell migration features, at least in the case
      of head and neck squamous cell carcinomas.

PMID- 11304581
TI  - Human hepatocellular carcinoma (HCC) cells require both alpha3beta1 integrin and
      matrix metalloproteinases activity for migration and invasion.
AB  - Hepatocellular carcinoma (HCC) is the most frequent malignant tumor of the liver;
      prognosis depends on the tendency to metastasize. Cancer cell invasion is
      regulated by proteolytic remodeling of extracellular matrix components and by
      integrin expression. We have shown that matrix metalloproteinase-2 (MMP-2) and
      membrane-type-1 matrix metalloproteinase (MT1-MMP) cleave Laminin-5 (Ln-5),
      stimulating cell migration. Here we report that all HCC cells express MT1-MMP,
      migrate on Ln-1 and Collagen IV, whereas only HCC cells that express alpha3beta1
      integrin secrete detectable levels of gelatinases, migrate on Ln-5, and invade
      through a reconstituted basement membrane (BM). Migration on Ln-5 is blocked by
      BB-94, an MMP inhibitor, and by MIG1, a monoclonal antibody that hinders
      migration on MMP-2-cleaved Ln-5. Invasion through a reconstituted BM is also
      inhibited by BB-94. HCC alpha3beta1-negative cells migrate on Ln-1 and Collagen
      IV, but not on Ln-5, and do not invade through a reconstituted BM, although they
      express MT1-MMP. Anti-alpha3beta1 blocking antibodies inhibit gelatinase
      activation, cell motility, and cell invasion through MATRIGEL: In vivo,
      alpha3beta1 integrin and Ln-5 are expressed in HCC tissue but not in normal
      liver. In conclusion, our data suggest that both alpha3beta1 integrin and
      gelatinase activity are required for HCC migration and invasion.

PMID- 11304582
TI  - A high frequency of allelic loss in oral verrucous lesions may explain malignant
      risk.
AB  - Verrucous carcinoma (VC), a variant of squamous cell carcinoma (SCC), is distinct
      from SCC in morphology and behavior. The underlying genetic changes involved in
      the development of VC and its precursor verrucous hyperplasia (VH) are unknown.
      This study determined whether chromosomal regions frequently lost during the
      development of SCC are also lost in the VH/VC variant. Twenty-five VH and 17 VC
      were analyzed for loss of heterozygosity (LOH) at 19 loci on 7 chromosome arms
      using microsatellite analysis. These data were compared with those from 47
      reactive hyperplasias, 92 dysplasias (54 low- and 38 high-grade), and 41 SCCS:
      The results showed that VC/VH shared many of the losses present in dysplasia/SCC
      but differed in two aspects. First, VC/VH showed early acquisition of loss,
      compared with a gradual accumulation of losses from dysplasias to SCC. The LOH
      pattern of VH was similar to that of high-grade dysplasia and sharply different
      from reactive hyperplasia. The loss in VH often involved multiple arms (in 60% of
      VH vs 0% of reactive lesions). Only a marginal elevation of loss was observed at
      9p (p = 0.06) and 4q (p = 0.05) from VH to VC because of the high degree of loss
      already present in VH. Second, a strikingly lower frequency of loss at 17p was
      noted in VH/VC compared with dysplasia/SCC and may indicate human papillomavirus
      (HPV) involvement. The finding of high-risk LOH profiles in VH may partly account
      for the high-progression risk seen for VH and also has potentially important
      clinical implications. The difficult pathological diagnosis of VH/VC from
      reactive hyperplasia frequently requires repeated biopsies and results in delay
      in diagnosis and significantly increased mortality/morbidity. Microsatellite
      analysis might facilitate this differential diagnosis.

PMID- 11304583
TI  - Quantitative analysis of promoter hypermethylation in laser-microdissected
      archival specimens.

PMID- 11304584
TI  - Analysis of the cellular composition of the arterial intima with modified en face
      techniques.

PMID- 11304585
TI  - Animal Models of Myopia: Learning How Vision Controls the Size of the Eye.
AB  - As they grow up, approximately 25% of children in the United States become myopic
      (nearsighted). A much smaller fraction become significantly hyperopic
      (farsighted), while the majority develop little or no refractive error and are
      emmetropic. The causes of refractive error, especially myopia, have been the
      subject of debate for more than a century. Some have held that myopia is
      primarily an inherited disorder, and others, that myopia is caused by protracted
      near work and, especially, by accommodation during protracted near work. It has
      not been possible, based solely on clinical observations, to resolve the relative
      roles of heredity versus environment in the development of refractive error. In
      the mid-1970s, several animal models were developed to study the mechanisms
      underlying refractive error. Using animal models, it was found that the visual
      environment exerts a powerful influence on refractive state by controlling the
      axial length of the eye during the postnatal developmental period. Although
      several species have been examined, three have emerged as primary models and have
      played complementary roles: tree shrews (mammals closely related to primates),
      chicks, and monkeys. Each has advantages and disadvantages. Collectively,
      research on animal models has provided evidence on three issues, namely that (1)
      the visual environment can produce refractive error; (2) an emmetropization
      mechanism normally guides eyes to low refractive error; and (3) under
      accommodation, rather than excessive accommodation, may cause myopia. Two decades
      of research on animal models have provided criteria that may be used to evaluate
      the usefulness of additional species as models of emmetropization.

PMID- 11304586
TI  - Recognizing pain and distress in laboratory animals.

PMID- 11304587
TI  - The angiosome concept applied to arteriovenous malformations of the head and
      neck.
AB  - Arteriovenous malformations remain a difficult clinical problem. There is very
      little understanding of the underlying pathogenesis of these lesions, and therapy
      frequently involves considerable risks with suboptimal outcomes. Recently, a
      comprehensive description of the angiosomes of the head and neck was completed in
      the authors' unit. It was noticed that the location of several clinically
      observed arteriovenous malformations in the head and neck seemed to correspond to
      the anatomic location of the choke anastomotic zones linking the angiosomes.
      Therefore, selective clinical angiograms were compared with those from the
      authors' previously performed fresh cadaver injection studies, in which they
      defined the angiosomes of the head and neck. In each patient, the location of the
      arteriovenous malformation corresponded directly to the choke vessel anastomotic
      zone linking two or more adjacent angiosomes. Clinical and pathologic
      ramifications of this observation are discussed.

PMID- 11304588
TI  - Remodeling of the temporomandibular joint following mandibular distraction
      osteogenesis in the transverse dimension.
AB  - Transverse mandibular distraction osteogenesis involves moving the osteotomized
      segments of the mandible in either a varus or valgus direction. This maneuver
      allows for widening of the bigonial distance or for a lateral shift of an
      asymmetric mandibular midline. During this process, a significant amount of
      torque is placed on the mandibular condyles, because they act as the pivot point
      for the mandibular translation. Although standard linear distraction osteogenesis
      induces transient, reversible changes in the temporomandibular joint, it is not
      known what effect the varus and valgus stresses of transverse distraction have on
      the temporomandibular joint. We therefore designed a study to document the
      temporomandibular joint changes following various degrees of transverse
      distraction. Bilateral transverse mandibular distraction was performed on 10
      adult, female mongrel dogs using an external, multiplanar mandibular distraction
      device. The distraction protocol was as follows: (1) complete osteotomy at the
      angle of the mandible, (2) 5-day latency period, (3) distraction rate of 1
      mm/day, (4) rhythm of one turn per day, (5) linear activation 16 to 30 mm
      bilaterally, and (6) 8-week consolidation period. A variety of varus and valgus
      distraction vectors were applied to the mandible only after 10 mm of initial
      linear distraction had been achieved. Posteroanterior and lateral cephalograms
      were performed throughout the entire process. Pre-distraction and post
      consolidation computed tomographic scans were also performed. Changes in
      mandibular conformation, axis of rotation, temporomandibular joint structure, and
      glenoid fossa changes were directly assessed by evaluating the postmortem
      craniofacial skeleton. The findings were compared with those of normal, age
      matched mongrel dog skulls. Significant remodeling changes were observed in the
      temporomandibular joints of all animals involved in the study. The mandibular
      condyles demonstrated varying degrees of flattening and erosion at all contact
      points with the craniofacial skeleton. In some cases, the condyle became part of
      the distraction regenerate process and was hypertrophied in all dimensions. The
      condyles were frequently displaced out of the glenoid fossa, particularly on the
      side in the direction of varus distraction. When the latter occurred, a new fossa
      was created on the undersurface of the zygomatic arch. Varying degrees of
      mandibular rotation in the sagittal plane were also observed, which led to
      abnormal torquing of the condyles in the coronal plane, depending on whether the
      axis of rotation occurred primarily around the condyle or around the distraction
      regenerate zone.In conclusion, transverse mandibular distraction is an effective
      means of producing a varus or valgus shift in the gonion relative to the
      midsagittal plane. However, unlike linear or angular mandibular distraction,
      transverse distraction has a multitude of nontransient effects on the
      temporomandibular joint. Therefore it must be emphasized that in clinical
      practice, transverse distraction should be used cautiously. One must also be
      aware that such a maneuver in distraction can have negative effects on the
      temporomandibular joint.

PMID- 11304589
TI  - Placement of endosteal implants in the zygoma after maxillectomy: a Cadaver study
      using surgical navigation.
AB  - Endosteal implants facilitate obturator prosthesis fixation in tumor patients
      after maxillectomy. Previous clinical studies have shown, however, that the
      survival of implants placed into available bone after maxillectomy is generally
      poor. Nevertheless, implants positioned optimally in residual zygomatic bone
      provide superior stability from a biomechanical point of view. In a pilot study,
      the authors assessed the precision of VISIT, a computer-aided surgical navigation
      system dedicated to the placement of endosteal implants in the maxillofacial
      area. Five cadaver specimens underwent hemimaxillectomy. The cadaver head was
      matched to a preoperative high-resolution computed tomograph by using implanted
      surgical microscrews as fiducial markers. The position of a surgical drill
      relative to the cadaver head was determined with an optical tracking system.
      Implants were placed into the zygomatic arch, where maximum bone volume was
      available. The results were assessed using tests for localization accuracy and
      postoperative computed tomographic scans of the cadaver specimens. The
      localization accuracy of landmarks on the bony skull was 0.6 +/- 0.3 mm (average
      +/- SD), as determined with a 5-df pointer probe; the localization accuracy of
      the tip of the implant burr was 1.7 +/- 0.4 mm. The accuracy of the implant
      position compared with the planned position was 1.3 +/- 0.8 mm for the external
      perforation of the zygoma and 1.7 +/-1.3 mm for the internal perforation. Eight
      of 10 implants were inserted with maximal contact to surrounding bone, and two
      implants were located unfavorably. Reliable placement of implants in this region
      is difficult to achieve. The technique described in this article may be very
      helpful in the management of patients after maxillary resection with poor support
      for obturator prostheses.

PMID- 11304590
TI  - The role of tissue expansion in the management of large congenital pigmented nevi
      of the forehead in the pediatric patient.
AB  - The authors present a cohort of 21 consecutive patients who had congenital
      pigmented nevi covering 15 to 65 percent of the forehead and adjacent scalp and
      who were treated at their institution within the last 12 years. All patients were
      treated with an expansion of the adjacent texture- and color-matched skin as the
      primary modality of treatment. The median age at presentation was approximately 1
      year; mean postoperative follow-up was 4 years. Nevi were classified according to
      the predominant anatomic areas they occupied (temporal, hemiforehead, and
      midforehead/central); some of the lesions involved more than one aesthetic
      subunit. The authors propose the following guidelines: (1) Midforehead nevi are
      best treated using an expansion of bilateral normal forehead segments and
      advancement of the flaps medially, with scars placed along the brow and at or
      posterior to the hairline. (2) Hemiforehead nevi often require serial expansion
      of the uninvolved half of the forehead to minimize the need for a back-cut to
      release the advancing flap. (3) Nevi of the supraorbital and temporal forehead
      are preferentially treated with a transposition of a portion of the expanded
      normal skin medial to the nevus. (4) When the temporal scalp is minimally
      involved with nevus, the parietal scalp can be expanded and advanced to create
      the new hairline. When the temporoparietal scalp is also involved with nevus, a
      transposition flap (actually a combined advancement and transposition flap
      because the base of the pedicle moves forward as well) provides the optimal hair
      direction for the temporal hairline and allows significantly greater movement of
      the expanded flap, thereby minimizing the need for serial expansion. (5) Once the
      brow is significantly elevated on either the ipsilateral or contralateral side
      from the reconstruction, it can only be returned to the preoperative position
      with the interposition of additional, non-hair-bearing forehead skin. Expansion
      of the deficient area alone will not reliably lower the brow once a skin
      deficiency exists. (6) In general, one should always use the largest expander
      possible beneath the uninvolved forehead skin, occasionally even carrying the
      expander under the lesion. Expanders are often overexpanded.

PMID- 11304591
TI  - The nasal dorsum as a donor site for the correction of alar, lobular, and
      columellar malformations.
AB  - There is a wide variety of donor sites available for minor nasal reconstructions
      involving alar, lobular, and columellar defects. Unfortunately, the problems all
      these sites have in common are that the color match may be unsatisfactory or that
      the end result may be marred by conspicuous scarring. If nasal-skin resources
      could be fully exploited, the elimination of these two important problems could
      become an obtainable goal. This article discusses the potential of the nasal
      dorsum as a donor site and describes methods that were used to try to achieve
      this goal. Skin redistribution, skin expansion, and skin distraction methods were
      used in 28 patients with alar (n = 13), lobular (n = 8), and columellar (n = 7)
      malformations and who had been followed up since the early 1980s.

PMID- 11304592
TI  - Breast cancer after augmentation mammaplasty: treatment by skin-sparing
      mastectomy and immediate reconstruction.
AB  - Breast conservation has been associated with poor cosmetic outcome when used to
      treat breast cancer in patients who have undergone prior augmentation
      mammaplasty. Radiation therapy of the augmented breast can increase breast
      fibrosis and capsular contraction. Skin-sparing mastectomy and immediate
      reconstruction are examined as an alternative treatment.Six patients with prior
      breast augmentation were treated for breast cancer by skin-sparing mastectomy and
      immediate reconstruction. One patient underwent a contralateral prophylactic skin
      sparing mastectomy. Silicone gel implants had been placed in the submuscular
      location in five patients and in the subglandular position in one patient a mean
      of 10.2 years (range, 6 to 20 years) before breast cancer diagnosis. The mean
      patient age was 41.3 years (range, 33 to 56 years). Four independent judges
      reviewed postoperative photographs to grade the aesthetic results in comparison
      with the opposite native or reconstructed breast. The American Joint Committee on
      Cancer staging was stage 0 in one patient, stage I for four patients, and stage
      II for one patient. Five of the six patients presented with a palpable breast
      mass. Latissimus dorsi flap reconstruction was performed in four patients
      (bilaterally in one) and a transverse rectus abdominis muscle (TRAM) flap was
      used in two patients. Three patients were treated by skin-sparing mastectomy with
      preservation of the breast implant (two patients with latissimus flaps, and one
      patient with a TRAM flap). The tumor location necessitated the removal of
      implants in two patients (one patient with a latissimus flap and one with a TRAM.
      A saline implant was placed under the latissimus flap after gel implant removal.
      The patient who underwent bilateral skin-sparing mastectomies desired
      explantation and placement of saline implants. No remedial surgery was performed
      on the opposite breast to achieve symmetry. Complications occurred in two
      patients at the latissimus dorsi donor site (seroma in one patient, and seroma
      and infection in one). Five patients underwent complete nipple reconstructions.
      The mean duration of follow-up was 33.6 months (range, 15.5 to 70.3 months), and
      there were no recurrences of breast cancer. The aesthetic results were judged to
      be good to excellent in all cases.Skin-sparing mastectomy and immediate
      reconstruction can be used in patients with prior breast augmentation, with good
      to excellent cosmetic results. Depending on the tumor and implant location, the
      implant may be preserved without compromising local control.

PMID- 11304593
TI  - Reduction mammaplasty with superior-lateral dermoglandular pedicle: another
      alternative.
AB  - During a period of 7.5 years, reduction mammaplasty using a superior-lateral
      dermoglandular pedicle was performed in 213 mammary glands in 112 patients. This
      procedure is a modification of the original technique by Skoog that takes
      advantage of its benefits but adds two basic premises: (1) to preserve the
      integrity of the galactophorous ducts for future nursing and (2) to cause less
      innervation injury. Patients were followed for an average of 28 months (range, 3
      months to 7.5 years). The quantity of extirpated tissue ranged from 310 to 1380
      g, with a median of 520 g. The nipple-areola complex migrated 5 to 14.5 cm
      (median, 7.8 cm). The most severe complication was partial necrosis of the nipple
      areola complex, which occurred in five cases (four patients). This complication
      occurred only during the first 2 years of the study, in breast resections larger
      than 800 g, and with migrations larger than 10 cm. This problem resulted in a
      modification of the technique, and the complication has not occurred for the past
      5 years. There were no important alterations in the sensibility of the nipple
      areola complex nor in the integrity of the galactophorous ducts. The long-term
      satisfaction of the patients was high. The authors present an easily designed and
      accomplishable technique that is applicable to patients with severe hypertrophy
      and gigantomastia. The technique has a high security index, and the integrity of
      the mammary gland is maintained to the maximum.

PMID- 11304594
TI  - Nylon versus polydioxanone in the correction of rectus diastasis.
AB  - Nylon and polydioxanone are two sutures commonly used to correct rectus
      diastasis. Polydioxanone, as an absorbable suture, has the advantage of not being
      palpable in thin patients. Because several forces act against the plication, an
      absorbable suture would not be efficient in these cases. In this study, two
      groups of 10 patients each were studied. These patients underwent abdominoplasty
      and correction of rectus diastasis. In the control group, 2-0 nylon was used to
      plicate the anterior aponeurosis and 0-polydioxanone was used in the experimental
      group. The tension of the abdominal wall was measured with a dynamometer in both
      groups. The width of rectus diastasis was measured 3 cm above and 2 cm below the
      umbilicus, using a computed tomography (CT) scan before the operation and 3 weeks
      and 6 months after surgery. The width of rectus diastasis was measured
      intraoperatively at the same levels. The data were analyzed by Student's t test.
      Both groups had similar abdominal wall tension on both levels. The diastasis
      recti was completely corrected at both levels, as confirmed by the 3-week
      postoperative CT scan and the 6-month CT scan. At the superior level, the width
      of the rectus diastasis on the preoperative CT scan (2.6 +/- 0.7 cm) was similar
      to the values obtained intraoperatively (2.7 +/- 0.6 cm), showing no significant
      statistical difference. At the inferior level, the largest difference between the
      preoperative CT scan and the intraoperative finding was 0.3 cm. In conclusion,
      the correction of rectus diastasis with 2-0 nylon and 0-polydioxanone was
      achieved and maintained after 6 months. CT scans are an accurate method for
      studying rectus diastasis and other muscles of the abdominal wall.

PMID- 11304595
TI  - Restoration of abdominal wall integrity as a salvage procedure in difficult
      recurrent abdominal wall hernias using a method of wide myofascial release.
AB  - The management of primary and recurrent giant incisional hernias remains a
      complex and frustrating challenge even with multiple alloplastic and autogenous
      closure options. The purpose of this study was to develop a reconstructive
      technique of restoring abdominal wall integrity to a subcategory of patients, who
      have failed initial hernia therapy, by performing superior and lateral myofascial
      release. Over a 1.5-year period, 10 patients with previously unsuccessful
      treatment of abdominal wall hernias, using either primary repair or placement of
      synthetic material, were studied. The patients had either recurrence of the
      hernia or complications such as infections requiring removal of synthetic
      material. The hernias were not able to be treated with standard primary closure
      techniques or synthetic material. The average defect size was 19 x 9 cm. Each
      patient underwent wide lysis of bowel adhesions releasing the posterior abdominal
      wall fascia to the posterior axillary line, subcutaneous release of the anterior
      abdominal wall fascia to a similar level, and complete removal of any synthetic
      material (if present). The abdominal domain was reestablished by releasing the
      laterally retracted abdominal wall. The amount of available abdominal wall tissue
      was increased by wide release of the cephalic abdominal wall fascia overlying the
      costal margin and the external oblique fascia and muscle laterally. If needed,
      partial thickness of the internal oblique muscle and its anterior fascia were
      also released laterally to perform a tension-free primary closure of the defect.
      All repairs were closed with satisfactory functional and aesthetic results. All
      alloplastic material was removed. Fascial release was limited so as to close only
      the hernia defect without tension. No significant release of the rectus sheath
      and muscle was needed. Good, dynamic muscle function was noted postoperatively.
      All repairs have remained intact, and no further abdominal wall hernias have been
      noted on follow-up.

PMID- 11304597
TI  - The versatility of the pudendal thigh fasciocutaneous flap used as an island
      flap.
AB  - The pudendal thigh flap is a sensate fasciocutaneous flap based on the terminal
      branches of the superficial perineal artery, which is a continuation of the
      internal pudendal artery. Several authors have reported using this axial
      patterned flap in a bilateral fashion to reconstruct the vagina, mostly in
      patients with vaginal atresia. The technique is simple, safe, and reliable, and
      no stents or dilators are required. The reconstructed vagina has a natural angle
      and is sensate. The donor site in the groin can be closed primarily with an
      inconspicuous scar. The distinct advantages of this flap widen its indications to
      several other pathologies. In this article, the authors report on the bilateral
      use of the flap to reconstruct a vagina in patients with congenital atresia (n =
      8) and after oncological resection (n = 5). Furthermore, the versatility of this
      island flap is also demonstrated by its use in a unilateral fashion in patients
      with recurrent or complex rectovaginal fistulas (n = 4) and in two patients with
      a defect of the posterior urethra in a heavily scarred perineum. All 31 pudendal
      thigh flaps survived completely. Some wound dehiscence was observed in two
      patients. Two other patients required a minor correction at the introitus of the
      vagina. The functional outcome was excellent in all patients, despite the
      presence of some hair growth in the flaps. This article discusses the expanding
      indications of this versatile flap and the refinements in operative technique.

PMID- 11304598
TI  - The natural history of the growth of the hand: I. Hand area as a percentage of
      body surface area.
AB  - The use of a patient's own hand as a tool to estimate the area of burn injury is
      well documented. The area of the palmar surface of one hand has been estimated to
      be 1 percent of the body surface area. The area of the palmar surface of the hand
      was measured to test the accuracy of this estimate and then compared with the
      body surface area as calculated by formulas in common use. This study also sought
      to determine the natural history of the growth of the hand to permit development
      of a readily available, bedside means of estimating hand area and body surface
      area. Bilateral hand tracings were obtained from 800 volunteers ranging in age
      from 2 to 89 years. The area of each tracing was determined using an integrating
      planimeter. The height and weight of each individual were measured, and his/her
      body surface area was calculated. The palmar hand's percentage of body surface
      area was determined by calculating the quotient for hand area divided by body
      surface area. Additionally, the width of the hand was measured from the ulnar
      aspect at the palmar digital crease of the small finger to the point where the
      thumb rested against the base of the index finger. The length of the hand was
      measured from the middle of the interstylon to the tip of the middle finger.
      These two figures were multiplied together to obtain a product which approximated
      the area of the hand. Based on the most commonly used DuBois formula for
      calculating body surface area, the area of palmar surface of the hand corresponds
      to 0.78 +/- 0.08 percent of the body surface area in adults. The percentage
      varies somewhat with age and reaches a maximum of 0.87 +/- 0.06 percent in young
      children. Multiplying the length of the hand by its width overestimates the area
      of the hand as determined by planimetry by only 2 percent. A patient's own hand
      may be used as a complementary, readily available template for estimation of burn
      area or other areas of disease or injury. In adults, the area of tracing of the
      outline of the hand is 0.78 percent of the body surface area, whereas in
      children, this number tends to be slightly higher. In the emergency room or on
      the wards, a simple product of length multiplied by width of the hand will
      closely approximate the area as determined by planimetry. This method allows a
      more accurate determination of the area of the palmar surface of the hand than
      the 1 percent estimate, which may lead to an overestimation of the size of a burn
      wound in adults.

PMID- 11304599
TI  - The devastating outcome of massive subcutaneous injection of highly viscous
      fluids in male-to-female transsexuals.
AB  - Illicit subcutaneous injections of massive quantities of highly viscous fluids
      are still performed, often by unqualified persons. Fifteen male-to-female
      transsexuals consulted the authors regarding their devastating long-term outcomes
      after the injection of up to 8 liters of alleged silicone or mineral oil to
      feminize their bodies. After a latency period of up to 17 years, these injections
      led to complications ranging from scarring and deformity to infections. These
      patients were treated conservatively for inflammation and infection or surgically
      by resection of the oil-infested areas. In view of the potential dangers,
      feminization by the injection of high-viscosity fluids should be soundly
      condemned.

PMID- 11304600
TI  - Evaluation of four methods of flexor tendon repair for postoperative active
      mobilization.
AB  - Active mobilization of repaired flexor tendons requires sufficient suture
      strength. This study was designed to investigate the suitability of four newly
      developed and comparatively strong tendon sutures for flexor tendon repair with
      active digital mobilization. Fifty fresh flexor digitorum profundus tendons were
      randomly assigned to five groups and repaired using the Tang, cruciate,
      Robertson, Silfverskiold, and modified Kessler suture methods. The repaired
      tendons were subjected to mechanical testing in an Instron tensile machine to
      determine the 2-mm gap formation force, ultimate strength, elastic modulus, and
      energy to failure of the sutures. The 2-mm gap formation forces of the sutures
      were 43.0 N for the Tang, 37.4 N for the cruciate, 25.0 N for the Robertson, 32.3
      N for the Silfverskiold, and 21.2 N for the modified Kessler methods. The
      ultimate strength of the sutures was 53.6 N for the Tang, 46.3 N for the
      cruciate, 41.6 N for the Robertson, 41.0 N for the Silfverskiold, and 24.7 N for
      the modified Kessler methods. Statistically, the gap formation force and ultimate
      strength were the highest in the Tang, higher in the cruciate, and the lowest for
      the Robertson and the modified Kessler methods. The elastic modulus of the
      repaired tendons, as represented by the linear slope of the force-displacement
      curve, was also statistically the largest in the Tang, larger in the cruciate,
      and lowest for the Robertson and modified Kessler methods. Energy to failure was
      statistically the largest in the Tang, higher in the cruciate, lower in the
      Silfverskiold and the Robertson, and the lowest for the modified Kessler methods.
      It was concluded that significant differences exist in mechanical properties of
      the newly developed tendon suture methods. Among the methods for tendon repair
      that were tested, the Tang and the cruciate sutures were the best candidates for
      flexor tendon repair in the hand with postoperative active mobilization because
      of their superior tensile strength, elastic properties, energy to failure, and
      reasonable operation time.

PMID- 11304601
TI  - Split-skin grafting with lidocaine-prilocaine cream: A meta-analysis of efficacy
      and safety in geriatric versus nongeriatric patients.
AB  - Although the efficacy and safety of the topical anesthetic EMLA cream (lidocaine
      prilocaine) have been studied extensively in children and adults, no published
      studies have focused on geriatric patients (>/=65 years of age). The objective of
      this study was to compare the efficacy and safety of EMLA in geriatric versus
      nongeriatric adults. A pooled analysis was made from original data of six studies
      of EMLA cream for split-skin grafting. The studies selected had a sufficient
      number of geriatric and nongeriatric adults and a uniform, standardized pain
      stimulus (split-skin grafting), pain rating (visual analogue scale, verbal rating
      scale) and adverse event recording. A total of 182 geriatric patients (82 aged 65
      to 74 years; 100 aged 75 to 96 years) and 221 nongeriatric EMLA-treated patients
      were evaluated. There was no difference in the efficacy of EMLA between geriatric
      and nongeriatric adults who underwent similar onset and duration of anesthesia.
      EMLA cream 1.5 g/10 cm2 applied for 2 to 5 hours had a similar anesthetic effect
      in both age groups. A dose of 3 g/10 cm2 gave no further benefit. In a geriatric
      population, EMLA cream provided effective cutaneous anesthesia for the cutting of
      split-skin grafts to the same extent as did infiltrated lidocaine. Adverse event
      frequency and severity were similar in geriatric and nongeriatric patients.
      Transient application site pallor, redness, and edema were the most frequent
      adverse events. Topical anesthesia with EMLA cream for split-skin grafting is as
      safe and effective in geriatric as in nongeriatric adults.

PMID- 11304602
TI  - Experimental assessment of the revascularization of acellular human dermis for
      soft-tissue augmentation.
AB  - The purpose of this experimental study was to determine whether acellular human
      dermis was capable of complete revascularization in a subcutaneous implantation
      site with various placement geometries. In young adult rabbit ears, four
      different sheet and rolled configurations were placed and harvested after 3, 7,
      14, and 28 days with silicone rubber microangiographic injections followed by
      histologic analysis. Revascularization of single-layer acellular human dermis
      occurred rapidly and was essentially complete by 14 days after surgery. No
      differences were observed in the ingrowth of vessels regardless of how the
      basement membrane was oriented. In rolled configurations, vascular ingrowth
      throughout the implant was slower and had not completely penetrated the grafts by
      28 days after surgery at study completion. Vessel ingrowth occurred through the
      implant surfaces contacting the surrounding soft tissue and along the open seam
      of the roll. No differences were seen whether the basement membrane was oriented
      on either the inside or the outside of the roll. Acellular human dermis is
      capable of significant revascularization of its compact collagen composition in
      the early postoperative period. In thicker geometries, the rate and completeness
      of vessel ingrowth are predictably slower. Whether complete revascularization of
      multilayered or rolled grafts is achieved cannot be determined from this study.

PMID- 11304603
TI  - Cranial reossification with absorbable plates.
AB  - The purpose of this study was to examine the effect of Lactosorb absorbable
      plates on bone healing across cranial bone defects in the rabbit skull. Two 10-mm
      diameter parietal skull defects were created in each of 20 rabbits, with one
      defect being placed on either side of the sagittal suture. In 10 rabbits, an
      absorbable plate was placed across both the inner and outer cortices of the left
      defect, and in the other 10 rabbits, an absorbable plate was placed across the
      outer cortex only of the left defect. The right defect always served as the
      control side, with no plate being placed across it. Rabbits were killed an
      average of 25 weeks postoperatively. Areas of reossification in the experimental
      and control defects of each rabbit were then measured, examined histologically,
      and compared. Growth across defects spanned by one plate was also compared with
      growth across defects spanned by two plates. Histologic and statistical analyses
      revealed no significant differences in reossification between the control and
      experimental defects in each animal and between the defects spanned by one versus
      two plates. This study suggests that these copolymer absorbable plates neither
      inhibit nor facilitate reossification across 10-mm diameter rabbit cranial
      defects.

PMID- 11304604
TI  - Discoidin domain receptors and their ligand, collagen, are temporally regulated
      in fetal rat fibroblasts in vitro.
AB  - The biochemical regulation of collagen deposition during adult cutaneous wound
      repair is poorly understood. Likewise, how collagen is perceived and modulated in
      fetal scarless healing remains unknown. Recently, discoidin domain receptors-1
      and 2 (DDR1 and DDR2) with tyrosine kinase activity have been identified as novel
      receptors for collagen. In light of these findings, it was speculated that the
      production of collagen receptors DDR1 and DDR2 by fetal fibroblasts may be
      temporally regulated to correlate with the ontogeny of embryonic scar formation.
      More specifically, because DDRs directly bind collagen and transmit the signals
      intracellularly, it was hypothesized that they may play an important role in
      fetal scarless healing by ultimately regulating and modulating collagen
      production and organization. As part of a fundamental assessment to elucidate the
      role of DDRs in scarless fetal wound repair, the endogenous expression of DDR1,
      DDR2, collagen I, and total collagen, as a function of fetal Sprague-Dawley rat
      skin fibroblasts of different gestational ages, representing scar-free (<E16.5
      days) and scar-forming (>E16.5) periods was determined. Using explanted dermal
      fibroblasts of gestational days E13.5, E16.5, E18.5, and E21.5 (term gestation =
      21.5 days) fetuses (n = 92), [3H]proline incorporation assay and Northern and
      Western blotting analysis were performed to compare the expressions of these
      molecules with scar-free and scar-forming stages of embryonic development. These
      results revealed a pattern of increasing collagen production with increasing
      gestational ages, whereas DDR1 expression decreased with increasing gestational
      age. This observation suggests that elevated levels of DDR1 may play an important
      role in scarless tissue regeneration by early gestation fetal fibroblasts. In
      contrast, DDR2 was expressed by fetal rat fibroblasts at a similar level
      throughout gestation. These data demonstrate for the first time the temporal
      expression of collagen and DDR tyrosine kinases in fetal rat fibroblasts as a
      function of gestational ages. Overall, these data suggest that differential
      temporal expression of the above-mentioned molecules during fetal skin
      development may play an important role in the ontogeny of scar formation. Future
      studies will involve the characterization of the biomolecular functions of these
      receptor kinases during fetal wound repair.

PMID- 11304606
TI  - Timing of microcirculatory injury from ischemia reperfusion.
AB  - The low flow state that results from ischemia and reperfusion injury is a
      potentially reversible process that is important in numerous clinical situations.
      However, the point in time during the course of reperfusion where tissue injury
      becomes irreversible is unknown. This experiment evaluated the continuum of
      tissue damage in skeletal muscle after ischemic insult by quantifying the number
      of flowing capillaries and percentage muscle necrosis in a male Wistar rat
      skeletal muscle model. A gracilis muscle flap was raised on the vascular pedicle
      of 39 male Wistar rats and examined at 832x using intravital videomicroscopy. The
      numbers of flowing capillaries in five consecutive high-power fields were counted
      for baseline values. The flap was then subjected to 4 hours of global ischemia
      (except in sham animals, n = 7) by placing a microvascular clamp on the pedicle
      artery and vein. Upon reperfusion, flowing capillaries were counted in the same
      five high-power fields at intervals of 5, 15, 30, and 60 minutes, then at 2 to 8
      (1-hour intervals), 24, and 48 hours. The gracilis muscle was then harvested at
      these intervals during reperfusion and assessed for viability. Compared with
      baseline, flowing capillaries from the ischemia and reperfusion group (mean +/-
      SEM) decreased significantly in the first 8 hours of reperfusion (7.7 +/- 0.2 to
      3.2 +/- 0.3, p < 0.001) with minimal change noted from 8 to 48 hours. Percentage
      muscle necrosis increased progressively in ischemia and reperfusion preparations
      from 1 to 7 hours of reperfusion (16.5 +/- 2.6 percent to 38.9 +/- 1.2 percent, p
      < 0.001). No significant change in muscle necrosis in the ischemia and
      reperfusion group was noted between 7 and 48 hours. Sham preparations showed no
      change in the number of flowing capillaries through 3 hours of reperfusion, with
      a slight decrease at 24 hours. This rat gracilis microcirculation skeletal muscle
      model demonstrates a heterogeneous reperfusion injury. The decrease in flowing
      capillaries correlated with the increase in percentage necrosis and appeared to
      stabilize at the 7- to 8-hour interval. This finding may have important
      implications for the timing of interventions aimed at minimizing tissue damage
      from ischemia-reperfusion.

PMID- 11304605
TI  - Comparison of long-term immunosuppression for limb transplantation using
      cyclosporine, tacrolimus, and mycophenolate mofetil: implications for clinical
      composite tissue transplantation.
AB  - This study compared the efficacy of long-term intermittent immunosuppression in
      preventing the rejection of a limb transplant across the strongest
      histocompatibility barrier in ACI --> Lewis rats using the conventional
      immunosuppressive agent cyclosporine-A and the newer immunosuppressive agents FK
      506 (tacrolimus) and RS-61443 (mycophenolate mofetil). The recipient animals were
      immunosuppressed daily for 14 days postoperatively, followed by long-term
      intermittent, twice-weekly immunosuppression using cyclosporine 25 mg/kg, RS
      61443 30 mg/kg, or FK-506 2 mg/kg. All three immunosuppressive agents were able
      to prolong the rejection of the skin component of a limb transplant compared with
      nonimmunosuppressed controls. Eight of nine animals receiving cyclosporine
      immunosuppression showed signs of rejection of the skin component of the limb
      transplant while continuing to receive long-term immunosuppression and had a mean
      rejection time of 61.6 days. Seven of 10 animals immunosuppressed with RS-61443
      also showed signs of rejection while still receiving immunosuppression, with a
      mean rejection time of 43.6 days. Nine of 10 animals receiving FK-506
      immunosuppression showed no signs of skin rejection, but died of bacterial
      pneumonia between 273 and 334 days after transplantation, with a mean rejection
      time of 296.1 days. There was no statistically significant difference between
      intermittent immunosuppression with cyclosporine and RS-61443, but FK-506 was
      significantly superior to both cyclosporine and RS-61443. The implication of this
      study is that FK-506, but not cyclosporine or RS-61443, is probably the only
      single immunosuppressive agent capable of preventing rejection of the skin
      component of a composite tissue transplant. Combination immunosuppression with FK
      506 and RS-61443, therefore, may be required to allow composite tissue
      transplantation to become a predictable clinical reality in the future.

PMID- 11304607
TI  - Investigation of the influence of keloid-derived keratinocytes on fibroblast
      growth and proliferation in vitro.
AB  - Keloids are disfiguring, proliferative scars that represent a pathological
      response to cutaneous injury. The overabundant extracellular matrix formation,
      largely from collagen deposition, is characteristic of these lesions and has led
      to investigations into the role of the fibroblast in its pathogenesis. Curiously,
      the role of the epidermis in extracellular matrix collagen deposition of normal
      skin has been established, but a similar hypothesis in keloids has not been
      investigated. The aim of this study was to investigate the influence of keloid
      epithelial keratinocytes on the growth and proliferation of normal fibroblasts in
      an in vitro serum-free co-culture system. A permeable membrane separated two
      chambers; the upper chamber contained a fully differentiated stratified
      epithelium derived from the skin of excised earlobe keloid specimens, whereas the
      lower chamber contained a monolayer of normal or keloid fibroblasts. Both cell
      types were nourished by serum-free medium from the lower chamber. Epithelial
      keratinocytes from five separate earlobe keloid specimens were investigated. Four
      sets of quadruplicates were performed for each specimen co-cultured with normal
      fibroblasts or keloid-derived fibroblasts. Controls consisted of (1) normal
      keratinocytes co-cultured with normal fibroblasts, and (2) fibroblasts grown in
      serum-free media in the absence of keratinocytes in the upper chamber.
      Fibroblasts were indirectly quantified by 3- (4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide colorimetric assay, with results confirmed by DNA
      content measurement, at days 1 and 5 after the co- culture
      initiation.Significantly, increased proliferation was seen in fibroblasts co
      cultured with keloid keratinocytes, as compared with the normal keratinocyte
      controls at day 5 (analysis of variance, p < 0.001). These results strongly
      suggest that the overlying epidermal keratinocytes of the keloid may have an
      important, previously unappreciated role in keloid pathogenesis using paracrine
      or epithelial-mesenchymal signaling.

PMID- 11304608
TI  - Thermal injuries to free flaps: better prevented than treated.

PMID- 11304609
TI  - Langerhans cell histiocytosis: orbital involvement as an unusual location.

PMID- 11304610
TI  - A simple method for determining the weight of the TRAM flap intraoperatively at
      the time of breast reconstruction.

PMID- 11304611
TI  - An osteotome for outfracture of the greater palatine foramen in cleft palate
      repair.

PMID- 11304613
TI  - Replantation.

PMID- 11304612
TI  - Replantation.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Describe the indications and contraindications for extremity replantation.
      2. Outline the sequence and technique of replantation. 3. Identify potential
      complications of replantation and recognize treatment options. 4. Assess the
      results of replantation in terms of function and costs versus benefits.

PMID- 11304614
TI  - Cervicofacial rejuvenation using ultrasound-assisted lipectomy.
AB  - This article discusses a technique of cervicofacial rejuvenation that involves
      ultrasound-assisted lipectomy. This method is indicated for those patients who
      might be early candidates for a rhytidectomy, and/or those with an adipose volume
      excess in the lower facial and cervical areas. The application of ultrasonic
      energy stimulates skin retraction and allows for the superficial fat to be more
      safely accessed than can be accomplished with conventional liposuction methods.
      This technique, along with a retrospective analysis of the first 26 cases treated
      with the technique, will be presented in this article.

PMID- 11304615
TI  - Alar rim deformities.
AB  - Alar disharmony is one of the most common abnormalities observed after a
      rhinoplasty. This article describes three classes in addition to Gunter's
      classifications of alar/columella deformities, which include concave ala, convex
      ala caused by convex lateral crus, and convex ala caused by thick alar tissues.
      These deformities are best visualized from the basilar view. The different
      surgical techniques for correction of true alar abnormalities are presented. The
      alar convexity, when it is the result of a misshapen cartilage, is corrected
      using a lateral crura spanning suture, posterior transection of the lateral
      crura, or transdomal suture. A thick ala, resulting in convexity, can be thinned
      through either a direct incision on the ala or an incision in the alar base. A
      lateral crura strut, an onlay graft, or a rim graft eliminates the concavity. For
      a slight retraction, an alar rim cartilage graft is an optimal choice. For
      significant alar retractions, the author's preferred technique is an internal V
      to-Y advancement, which is described in detail. An elliptical excision of the
      alar lining will effectively correct the hanging ala. These techniques have been
      used to correct alar disharmonies on 58 patients. One patient from the V-Y
      advancement group exhibited a small area of alar necrosis, and two early patients
      demonstrated an overcorrection; all were easily resolved with revision surgery.
      By carefully identifying nasal base and alar abnormalities, harmony can be
      established to correct an undesirable appearance.

PMID- 11304616
TI  - Alar rim deformities.

PMID- 11304617
TI  - Alar rim deformities.

PMID- 11304618
TI  - Anchor subperiosteal forehead lift: from open to endoscopic.

PMID- 11304619
TI  - Anchor subperiosteal forehead lift: from open to endoscopic.

PMID- 11304620
TI  - Confusion among perforator flaps: what is a true perforator flap?

PMID- 11304621
TI  - Median lower lip fissure.

PMID- 11304622
TI  - Left-handedness in plastic surgery: asset or liability?

PMID- 11304630
TI  - John Yelloly (1774-1842).

PMID- 11304631
TI  - The medical education of Sir Thomas Browne, a seventeenth-century student at
      Montpellier, Padua, and Leiden.

PMID- 11304632
TI  - Challenges of a surgeon at war 100 years ago.

PMID- 11304633
TI  - The Grassi-Calandruccio controversy. Who is wrong? Who is right?

PMID- 11304634
TI  - Purkyne's heautognosis.

PMID- 11304635
TI  - Saint Erasmus, patron saint of gastrointestinal and liver diseases.

PMID- 11304636
TI  - Polycythaemia vera: Osler-Vaquez disease.

PMID- 11304637
TI  - Catalogue of the library of Sir John Forbes (1787-1861) MD Edin FRCP Lond FRS.
      Part I: Some general works.

PMID- 11304638
TI  - The Mozarteum's skull: a historical saga.

PMID- 11304639
TI  - The anniversary significance of William Osler's birthday: 12 July.

PMID- 11304640
TI  - The cost of therapy.

PMID- 11304641
TI  - A steady-state evaluation of the bioavailability of chronotherapeutic oral drug
      absorption system verapamil PM after nighttime dosing versus immediate-acting
      verapamil dosed every eight hours.
AB  - To compare the steady state pharmacokinetics of the 200 mg verapamil PM CODAS
      (chronotherapeutic oral drug absorption system) formulation dosed nightly versus
      immediate-acting verapamil 80 mg tablets dosed three times daily, an open-label,
      single-dose, two-treatment, two-period, two-sequence, balanced, randomized
      crossover study was performed with a 7-day washout between two treatment periods.
      Twenty-four healthy male subjects completed the study. All subjects received
      CODAS verapamil PM 200 mg under fasting conditions dosed at nighttime or
      verapamil 80 mg dosed three times daily at 8-hour intervals in a randomized
      fashion. CODAS verapamil PM 200 mg dosed at night for 5 days results in a plasma
      profile with a lag time of approximately 4 hours suitable for nighttime dosing.
      Significantly lower plasma concentrations of both enantiomers of verapamil and
      norverapamil resulted in lower peak-to-trough fluctuations and should ensure the
      safety of the product. Both medications tested in this study were well tolerated
      by the group of healthy volunteers.

PMID- 11304642
TI  - Analysis of the hemodynamic effects of heparinase I and protamine sulfate in the
      systemic and hindlimb vascular beds of the male rat.
AB  - The effects of heparinase I and protamine sulfate on the mean arterial pressure
      and hindlimb perfusion pressure in the male rat were studied. With institutional
      approval, 21 male Sprague-Dawley rats were anesthetized, and the carotid artery
      and abdominal aorta were cannulated by cutdown. To isolate the hindlimb, a semi
      closed peristaltic perfusion circuit was used. Heparinase I or protamine sulfate
      was injected into the hindlimb vascular bed, and changes in mean arterial
      pressure and hindlimb perfusion pressure were recorded. Analysis of variance with
      a post hoc Scheffe's test was used for statistical analysis, and a P value less
      than.05 was considered significant. Increasing doses of heparinase I caused a
      small but significant decrease in mean arterial pressure only at the two highest
      doses. At all doses, hindlimb perfusion pressure was significantly less than the
      baseline value and than the value with saline administration at 1 minute. At the
      clinically applicable doses of heparinase I (0.625 and 1.25 IU/kg), the decrease
      in hindlimb perfusion pressure was less than 7. At the next two higher doses, the
      change was less than 15%. The vehicle of heparinase caused a significant decrease
      in mean arterial pressure (from -15% to -30%) and hindlimb perfusion pressure
      (from -10% to -20%). Increasing doses of protamine sulfate caused an increase in
      hindlimb perfusion pressure from baseline, including a 58% change with the 10
      mg/kg dose. There was a transient decrease in mean arterial pressure, which
      peaked 4 to 5 minutes after injection, to a 21% decrease from baseline with the 5
      and 10-mg/kg doses. Heparinase I caused vasodilation in the hindlimb and
      decreased mean arterial pressure only at supraclinical doses. Protamine sulfate
      caused a significant dose-dependent increase in hindlimb vascular resistance and
      a transitory decrease in mean arterial pressure.

PMID- 11304643
TI  - In vivo binding characteristics of phenytoin to serum proteins in monotherapy for
      adults with epilepsy.
AB  - The aim of the present study was to determine the binding characteristics of
      phenytoin (PHT) to serum proteins in the adults. Binding parameters of PHT to
      serum proteins in our study were compared with in vivo or in vitro binding
      parameters of PHT to serum proteins reported by other investigators. Serum
      samples in the study were obtained from 36 adult patients (17 men, 19 women)
      receiving PHT monotherapy. A total of 43 steady-state concentrations were
      analyzed in the study. Patients' age ranged from 16 to 73 years (mean [SD], 42.9
      [14.7] years). The in vivo population binding parameters of PHT to serum proteins
      and theoretical minimal unbound serum PHT fraction (fu) were determined using an
      equation derived from the Scatchard equation. The association constant (K) was
      0.014 L x micromol(-1), whereas the total concentration of binding sites (n(Pt))
      was 754 micromol x L(-1). The number of binding sites per albumin molecule (n)
      was 1.16, whereas binding ability (n.K) was 0.016 L x micromol(-1). The fu was
      0.087. The n.K is approximately 1.2 times higher in PHT monotherapy patients of
      Pospisil and Perlik (ie, 0.0191 L x micromol(-1)) than in all our patients. The
      association constant is approximately 1.3 times higher in the in vitro study of
      Monks et al (ie, 0.0186 L x micromol(-1)) than in our study, whereas n is similar
      between the two studies. The fu in our patients is similar to the unbound serum
      PHT fraction in patients receiving PHT therapy reported by Richens (ie, 0.1). Our
      results suggest that there may be small differences in the binding affinity of
      PHT to serum proteins between in vivo and in vitro studies. The unbound serum
      fraction of PHT in epileptic patients can be assumed to be relatively constant in
      the therapeutic concentration range of PHT.

PMID- 11304644
TI  - Androgens, anabolic-androgenic steroids, and inhibitors.
AB  - Androgens are steroid hormones responsible for male sexual characteristics,
      testosterone being the principal androgen secreted by the testes. Androgens have
      both masculinizing and growth-stimulating or anabolic effects. Synthetic analogs
      of androgens have been used by professional, as well as amateur, athletes for
      possible performance enhancement. The subject of androgens, pharmacologic
      actions, organ system effects, therapeutic uses, adverse reactions, and abuse
      potential are reviewed.

PMID- 11304645
TI  - Pulsed inotropic therapy in chronic congestive heart failure: a review of the
      literature.
AB  - Some centers in the United States continue to use (periodic) pulsed inotropic
      therapy in the management of severe congestive heart failure. Although there have
      been large, randomized, well-designed trials of oral inotropes in chronic heart
      failure, studies evaluating intravenous agents have been smaller and often of
      inferior design. Review of available intravenous inotrope studies in chronic
      congestive heart failure found improved clinical status with treatment. Although
      studies suggest clinical benefit is achieved at a cost of increased mortality, no
      study demonstrated a statistically significant difference. Large, randomized
      studies are needed to define the role of intravenous inotropic therapy in various
      heart failure groups, establish its safety, and explore its adjunctive use to
      enhance oral therapy.

PMID- 11304646
TI  - Homocysteine and arteriosclerosis: established risk factor or new illusion?
AB  - Homocysteine is an amino acid and a product of methionine metabolism that is
      metabolized through two different enzymatic pathways: transsulfuration and
      remethylation. Vitamin B6 is important in homocysteine transsulfuration, whereas
      folate and vitamin B12 play significant roles in homocysteine remethylation. The
      hyperhomocysteinemia offers an explanation for observations on human
      arteriosclerosis that are difficult to explain by the cholesterol/fat approach.
      However, hyperhomocysteinemia can influence cognitive functions in the elderly.
      The causes of hyperhomocysteinemia are inherited and acquired. The treatment of
      hyperhomocysteinemia varies with underlying cause; generally, vitamin
      supplementation (with folic acid and vitamins B6 and B12) is effective in
      reducing homocysteine concentrations. Also, specific recommendations, food
      fortification with folic acid, and preventive strategies in European countries
      (as in United States) are necessary to decrease cardiovascular morbidity and
      mortality.

PMID- 11304647
TI  - Acute ketamine intoxication treated by haloperidol: a preliminary study.
AB  - In an open, double-blind study of phencyclidine intoxication, 21 white male
      subjects were later found to have instead ingested ketamine. These subjects were
      divided into two cohorts, one treated with 5 mg intramuscular haloperidol and the
      second with an active placebo. Assessment with the Brief Psychiatric Rating Scale
      revealed significant reduction in symptoms with haloperidol.

PMID- 11304649
TI  - Sudden death in athletes.

PMID- 11304648
TI  - Osteoarticular tuberculosis: current diagnosis and treatment.
AB  - Tuberculous synovitis frequently presents as a monoarthritis of weight-bearing
      joints such as the hip, knee, or ankle. Owing to its low incidence in developed
      countries, the diagnosis is often delayed for months to years. Early diagnosis
      with a synovial biopsy permits prompt antituberculous therapy and substantially
      improves the prospect of preservation of joint structure and function. Initial
      treatment typically includes combination therapy with four drugs (isoniazid,
      rifampin, pyrazinamide, and streptomycin or ethambutol) because of the frequency
      of isoniazid resistance. Antimicrobial therapy should be of at least 9 months'
      duration, longer in immunocompromised hosts. Partial synovectomy and other
      surgical procedures should be restricted to joints with severe cartilage
      destruction, large abscesses, joint deformity, multiple drug resistance, or
      atypical mycobacteria.

PMID- 11304650
TI  - Are we overregulated?

PMID- 11304651
TI  - Nicardipine to control mean arterial pressure after cardiothoracic surgery in
      infants and children.
AB  - Nicardipine is the first intravenously administered dihydropyridine calcium
      channel blocker. Its primary physiologic action includes vasodilatation with
      limited effects on the inotropic and dromotropic function of the myocardium.
      Several previous reports document its use in adult patients for pharmacologic
      control of blood pressure. The current report describes the use of nicardipine to
      control mean arterial pressure (MAP) in nine infants and children after
      cardiothoracic surgical procedures. The patients ranged in age from 6 days to 9
      years (mean, 3.3 +/- 4.1 years) and in weight from 4.1 to 49 kg (mean, 15.3 +/-
      14.4). The surgical procedures included aortic coarctation repair (three), repair
      of tetralogy of Fallot (two), arterial switch for transposition of the great
      vessels (two), pulmonary valvotomy (one), and aortic valvotomy (one). The target
      systolic blood pressure was 90 mm Hg in patients younger than 4 years of age and
      < or = 110 mm Hg in patients 5 years of age or older. The nicardipine infusion
      was started at 5 microg/kg/min in all patients. The target blood pressure was
      achieved within 15 minutes in eight of nine patients. One patient required an
      initial infusion rate of 10 microg/kg/min to achieve the target blood pressure.
      The maintenance infusion rate varied from 2.5 to 5.5 mcg/k/min (mean 3.0 +/-
      1.1). The duration of the infusion varied from 30 to 42 hours (mean, 37.4 +/-
      4.2). In the nine patients, nicardipine was infused for a total of 337 hours. No
      adverse effects such as excessive hypotension were noted. Nicardipine is an
      effective agent for controlling MAP after cardiothoracic surgical procedures in
      infants and children.

PMID- 11304652
TI  - Effect of activated charcoal on diethylcarbamazine absorption in humans.
AB  - We investigated the effect of the oral binder-activated charcoal on the excretion
      of diethylcarbamazine. Six healthy volunteers were given 150 mg
      diethylcarbamazine with 350 mL water each. One and 2 weeks later, they received
      150 mg diethylcarbamazine plus 7.5 and 15 g activated charcoal, respectively, in
      350 mL water as a charcoal slurry. Urinary levels of diethylcarbamazine were
      measured spectrophotometrically from 1 to 72 hours after ingestion in three
      different periods. Treatment with activated charcoal led to 5.4% urinary recovery
      of diethylcarbamazine, decreased excretion rate, and a much lower plateau
      indicator of reduced absorption. Activated charcoal reduces the absorption and
      urinary excretion rate of diethylcarbamazine by adsorbing it in the
      gastrointestinal tract.

PMID- 11304653
TI  - Impaired activation of the fibrinolytic system in children with Henoch-Schonlein
      purpura: beneficial effect of hydrocortisone plus Sigma-aminocaproic acid therapy
      on disappearance rate of cutaneous vasculitis and fibrinolysis.
AB  - Systemic vasculitis is a predominant clinical symptom in Henoch-Schonlein purpura
      (HSP), and some studies suggested that decreased blood fibrinolytic activity, as
      well as blood platelets, is of importance in the development of cutaneous
      vasculitis. Although patients with HSP have normal blood coagulation, little is
      known about the fibrinolytic system. On the other hand, it is known that the
      focus of Sigma-aminocaproic acid (EACA) activity in vivo is probably the blood
      platelet-vessel wall interaction or a vascular component alone. The aim of this
      study was, therefore, to investigate blood coagulation and fibrinolytic system as
      well as the effect of hydrocortisone (H) plus EACA therapy (Group I) on plasma
      antithrombin-III (AT-III), alpha1-proteinase inhibitor (alpha1-PI), alpha2
      antiplasmin (alpha2-A), alpha2-macroglobulin (alpha2-M) activity, fibrinogen and
      plasminogen concentrations in plasma, euglobulin clot lysis time (ELT), and
      disappearance rate of cutaneous vasculitis in 14 children with HSP aged 7.6 +/-
      3.1 (SD) years. Ten patients (8.6 +/- 2.5 years old) were treated with H alone
      (Group II), and 8 healthy, age-matched children served as controls. Plasma
      proteinase inhibitor activity was estimated with the kinetic method using
      Boehringer chromozyme tests before administration of H (9.2 +/- 3.3 mg/kg/d,
      i.v.) plus EACA (140 +/- 52 mg/kg/d, p.o.) for 5.93 +/- 2.05 days, and 24 hours
      after the last dose of EACA, as well as before and after treatment with H alone
      (8.25 +/- 1.74 mg/kg/24 h, i.v.) for 7.1 +/- 1.2 days. It was found that patients
      with HSP had the initial fibrinogen and plasminogen plasma concentrations
      significantly increased compared with the controls (Group I: 3.93 +/- 1.3 g/L and
      124 +/- 38%; Group II: 4.24 +/- 0.89 g/L and 134 +/- 42% vs. 2.96 +/- 0.34 g/L,
      and 90 +/- 14%, respectively). Also, there was a marked decrease of the initial
      plasma alpha2-A activity in Group II compared with the controls (0.69 +/- 0.29
      vs. 0.94 +/- 0.11 IU/mL, respectively, t = 2.33, P <.045). Both treatment
      regimens significantly improved fibrinolysis, which manifested as a shortening of
      ELT, but the mean values of this parameter remained within normal range. After
      treatment with H plus EACA, the skin lesions started to disappear significantly
      faster compared with the H alone regimen (2.28 +/- 0.45 days vs. 4.12 +/- 1.05, t
      = 4.41, P <.0023). In four of six patients receiving H plus EACA therapy, an
      approximately 20% decrease of systolic and diastolic arterial blood pressure
      lasting for 5 to 7 hours after administration of EACA was observed. These results
      may suggest that children with HSP have impaired plasma fibrinolytic activity and
      that an increased release of plasminogen activator inhibitor-1 (PAI-1) might be,
      at least in part, responsible for this phenomenon. Concomitant use of H
      (approximately 10 mg/kg/d) plus EACA (approximately 100 mg/kg/d) for a few days
      opens new therapeutic possibilities in some children with HSP.

PMID- 11304655
TI  - Pharmacodynamic effects of dopamine stratified by race.
AB  - The purpose of this investigation was to evaluate the effects of dopamine on
      heart rate (HR), systolic blood pressure (SBP), aldosterone, plasma renin
      activity (PRA), bradykinin, prolactin, corticotropin (ACTH), urinary output (UO),
      and urinary sodium (UNa) stratified by race. Sixteen healthy age- and weight
      matched Caucasian and African American male subjects participated in this single
      blind, three-phase study. The three phases included the following treatments and
      assessments: (i) 90-minute infusion of D(5)W 100 mL/h and control piggyback
      (control period); (ii) 90-minute infusion D(5)W 100 mL/h and 3 microg/kg/min
      dopamine (dopamine phase); (iii) assessments repeated 24 hours after dopamine
      administration (washout period). Plasma was analyzed for dopamine concentrations.
      Dopamine significantly increased HR and SBP across the study population. In
      addition, UO and UNa increased, prolactin was reversibly depressed, bradykinin
      and ACTH were unchanged, and aldosterone significantly rebounded on washout. With
      regard to race differences, SBP significantly increased in African Americans
      compared with Caucasians, and UNa significantly increased in Caucasians compared
      with African Americans. In summary, 3 microg/kg/min dopamine produced significant
      renal, hormonal, and hemodynamic changes in healthy men. Selected effects varied
      by race.

PMID- 11304654
TI  - Impact of oral bases on aluminum absorption.
AB  - Control of hyperphosphatemia in renal failure is often difficult to achieve.
      Although calcium-containing phosphate binders have become the preferred phosphate
      binders, many patients require the addition of an aluminum-containing phosphate
      binder (APB). Enhanced aluminum absorption has been noted when APBs are
      administered with citrate-containing products such as citrate/citric acid
      solution (CCA). Alternative phosphate binders such as calcium acetate may also
      increase aluminum absorption. This study investigated the effect of CCAs on
      aluminum absorption when aluminum antacids (APBs) were administered concurrently
      and 2 hours apart. The effects of the alternative alkalinizing agent sodium
      bicarbonate and the alternate phosphate binding agent calcium acetate on aluminum
      absorption were also studied. During five 2-day phases, ten normal volunteers
      randomly received three times daily with standardized meals aluminum hydroxide
      alone and concurrently with NaHCO3, calcium acetate, CCA, or with CCA 2 hours
      postprandially. Twenty-four hour urines were collected on the second day of each
      phase and aluminum excretion was determined using inductively coupled plasma
      emission spectroscopy. Urine aluminum excretion was statistically significantly
      (P <.005) elevated in subjects receiving Al(OH)3 and CCA both with meals, 269.3
      +/- 146.3 microg/d, and 2 hours after meals, 303.3 +/- 142.9 microg/d, compared
      with 79.2 +/- 52.0 microg/d during treatment with Al(OH)3 alone. Administration
      of CCA 2 hours after APB does not permit the safe use of these agents
      concurrently. Concomitant administration of sodium bicarbonate and calcium
      acetate with APBs appears to be safe, as aluminum absorption was not affected.

PMID- 11304656
TI  - In vivo pharmacokinetics and anti-anaphylactic activity of the novel mast cell
      inhibitor 4-(4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131).
AB  - WHI-P131 is a novel dimethoxyquinazoline compound that is a potent inhibitor of
      Janus kinase-3-(JAK3)-dependent mast cell responses. In the present study, the
      authors investigated the anti-anaphylactic activity and pharmacokinetics of WHI
      P131 in mice. After intraperitoneal (i.p.) administration of two consecutive
      bolus doses of 25 mg/kg injected 30 min apart at dose level of 25 mg/kg, WHI-P131
      was rapidly absorbed with an observed C(max) of 82.6 microM, which is higher than
      the target concentration of 30 microM, at which WHI-P131 abrogates mast cell
      responses in vitro and the time to reach the maximum plasma concentration
      (t(max)) was 10.0+/-2.9 min. At a nontoxic 50 mg/kg dose level, WHI-P131
      prevented compound 48/80-induced mast cell histamine release and fatal
      anaphylaxis in mice. Further development of WHI-P131 may provide the basis for
      new and effective treatment as well as prevention programs for mast cell mediated
      allergic reactions in clinical settings.

PMID- 11304657
TI  - Pharmacodynamic optimization of warfarin therapy II.
AB  - A pharmacodynamic (E(max)) model for optimizing warfarin initiation had
      previously been reported. This study assessed the validity of this model,
      adjusted further for age in both the initial cohort and another cohort distinct
      from that used for the formulation of the model. Thirty-one patients undergoing
      oral anticoagulation for mainly cardiac indications were recruited from Kuala
      Lumpur. Thirty-four patients undergoing oral anticoagulation for deep vein
      thrombosis were recruited from Cambridge. They were studied for their
      anticoagulant response to the initiation of warfarin. The former were intuitively
      dosed after a 2-day loading of 10 mg warfarin/d. The latter all were commenced on
      warfarin via a standard 4-day induction protocol of Fennerty et al that allows
      early estimation of the required maintenance dose. The actual maintenance doses
      in both cohorts were compared with their predicted doses on the initiation of
      therapy that was calculated both from this model and from the induction protocol
      of Fennerty et al. The third day's international normalized ratio and age
      combination was additive in terms of their influence on the maintenance dose. The
      predictive model in both cohorts returned similar results and explained at least
      two thirds of the interindividual variability in warfarin maintenance dose
      requirements, whereas the induction protocol of Fennerty et al explained only one
      third of this interindividual variability. Use of this model in the form of the
      included nomogram should be able to decrease both the occurrence of either under-
      or overanticoagulation as well as the time taken to initiate treatment and decide
      the correct maintenance dose during the initiation of oral anticoagulation with
      warfarin in hospitals. A prospective evaluation of the nomogram is recommended.

PMID- 11304658
TI  - Cox-2-specific inhibitors: definition of a new therapeutic concept.
AB  - Nonsteroidal anti-inflammatory drugs have been a mainstay in the treatment of
      inflammatory diseases such as rheumatoid arthritis. However, these agents can
      result in severe and occasionally life-threatening adverse effects that can limit
      therapeutic benefit. Progress toward safer anti-inflammatory therapy was aided by
      the discovery that cyclooxygenase (COX) exists as two isozymes, COX-1 and COX-2.
      Both isozymes form prostaglandins that support physiologic functions; however,
      the formation of proinflammatory prostaglandins is catalyzed by COX-2. Inhibition
      of COX-2 accounts for the anti-inflammatory and analgesic action of NSAIDs;
      however, concurrent inhibition of COX-1 inhibits prostaglandin-dependent
      mechanisms such as gastroduodenal mucosal defense and platelet aggregation. This
      inhibition is the basis of the gastrointestinal toxicity and bleeding
      characteristic of these drugs. These findings led to the hypothesis that agents
      that selectively inhibit COX-2 would possess anti-inflammatory and analgesic
      action but would spare COX-1, thereby avoiding adverse effects in the
      gastrointestinal tract and platelets. Selective COX-2 inhibitors are now
      available. The novelty of these agents has raised questions in the medical
      community as to what constitutes selectivity for COX-2. This review outlines the
      criteria that must be met to characterize a compound as COX-2-specific. Clinical
      evidence of clear improvement in gastrointestinal tolerability and safety must be
      demonstrated in addition to complementary evidence of COX-2 selectivity obtained
      from enzyme, biochemical, and clinical pharmacology evaluations.

PMID- 11304659
TI  - Clinical therapeutic conference: congestive heart failure therapy.

PMID- 11304660
TI  - Pediatric exclusivity and genericizing pharmaceuticals.

PMID- 11304661
TI  - Cardiovascular and renal effects of COX-2-specific inhibitors: recent insights
      and evolving clinical implications.

PMID- 11304662
TI  - Cyclooxygenase-2--specific inhibitors and cardiorenal function: a randomized,
      controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis
      patients.
AB  - BACKGROUND: Arthritis and hypertension are common comorbid conditions affecting
      elderly adults. Use of nonsteroidal anti-inflammatory drugs in patients treated
      with antihypertensive medication can lead to destabilization of blood pressure
      control and other cardiorenal events. The potential for similar interactions with
      cyclooxygenase-2-specific inhibitors has not been fully explored. The authors
      evaluated the cardiorenal safety of two new cyclooxygenase-2-specific inhibitors,
      celecoxib and rofecoxib. METHODS: This study was a 6-week, randomized, parallel
      group, double-blind trial in patients with osteoarthritis who were > or =65 years
      of age and were taking antihypertensive agents. Patients received once-daily
      celecoxib 200 mg or rofecoxib 25 mg. The primary endpoints were the development
      of edema, changes in systolic blood pressure, and changes in diastolic blood
      pressure as measured at any time point in the study. Measurements occurred at
      baseline and after 1, 2, and 6 weeks of treatment. FINDINGS: Eight hundred ten
      patients received study medication (celecoxib, n = 411; rofecoxib, n = 399).
      Nearly twice as many rofecoxib- compared with celecoxib-treated patients
      experienced edema (9.5% vs. 4.9%, P = 0.014). Systolic blood pressure increased
      significantly in 17% of rofecoxib- compared with 11% of celecoxib-treated
      patients (P = 0.032) at any study time point. Diastolic blood pressure increased
      in 2.3% of rofecoxib- compared with 1.5% of celecoxib-treated patients (P =
      0.44). At week 6, the change from baseline in mean systolic blood pressure was
      +2.6 mmHg for rofecoxib compared with -0.5 mmHg for celecoxib (P = 0.007).
      CONCLUSIONS: Patients taking antihypertensive therapy and receiving
      cyclooxygenase-2-specific inhibitors should be monitored for the development of
      cardiorenal events. Patients receiving celecoxib experienced less edema and less
      destabilization of blood pressure control compared with those receiving
      rofecoxib.

PMID- 11304663
TI  - Plasma proteinase inhibitor activity and hemostasis tests in children with
      nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon
      aminocaproic acid treatment regimens: a preliminary report.
AB  - Neutrophil-derived proteinases cause glomerular injury by proteolysis of the
      glomerular basement membrane and alterations in glomerular metabolism. Recently,
      a marked elevation of the plasma elastase complex with alpha1-proteinase
      inhibitor (alpha 1-PI) both in the acute phase and during remission of nephrotic
      syndrome (NS) compared with age-matched controls was reported. In experimental
      immune-mediated glomerulonephritis epsilon-aminocaproic acid (EACA) significantly
      reduced albuminuria, and it was suggested that this may be linked with the
      antiproteolytic activity of the drug. We studied plasma antithrombin III (AT
      III), alpha 1-PI, alpha 2-antiplasmin (alpha 2-A), alpha 2-macroglobulin (alpha 2
      M) activity, and some blood coagulation and fibrinolysis tests in children with
      frequently relapsing prednisone-responsive NS. Also, the effect of prednisone
      alone (Group I, n = 9) and prednisone plus EACA (Group II, n = 10) treatment
      regimens on the studied parameters was estimated. All investigations were
      performed on admission to the hospital and after approximately 13 days of
      prednisone alone therapy (Group I), as well as before the administration of
      prednisone plus EACA and 24 hours after the last dose of EACA, ie, after
      approximately 5 days of treatment (Group II). Prednisone was administered at the
      usual dose of approximately 2 mg/kg/d and EACA was given orally at the doses of
      72 to 230 mg/kg of body weight per day for 3 to 10 days. In the acute phase of
      disease, NS patients (n = 19) were shown to have a statistically significant
      decrease of plasma AT-III (16.4 +/- 4.7 vs. 21.9 +/- 2.5 IU/mL) and alpha 1-PI
      (1.28 +/- 0.6 vs. 1.97 +/- 0.34 IU/mL) activity, as well as a marked increase in
      plasma alpha 2-M activity (14.96 +/- 5.81 vs. 9.6 +/- 1.6 IU/mL), and fibrinogen
      concentration (5.51 +/- 1.78 vs. 2.96 +/- 0.34 g/L) compared to the age-matched
      controls; no significant changes in plasma alpha 2-A activity, plasminogen
      concentration, euglobulin clot lysis time, activated partial thromboplastin time
      (APTT), or thromboplastin time were noted. In children treated with prednisone
      alone, a marked increase in plasma AT-III (by 76%, P < 0.001) and alpha 2-A (36%,
      P < 0.019) activity, and a significant decrease of the plasma fibrinogen
      concentration (6.07 +/- 1.66 vs. 3.17 +/- 1.64 g/L, P < 0.001), and APTT (45.1 +/
      7.6 vs. 33.8 +/- 4.4 s, P < 0.001) were found. Prednisone plus EACA therapy
      resulted in a significant increase in plasma AT-III activity (by 53%, P < 0.003),
      whereas plasma fibrinogen concentration and APTT remained unchanged. However,
      statistically significant differences between the pre- and posttreatment plasma
      AT-III, alpha 1-PI, and alpha 2-A activities in these patients were observed.
      There was also a relationship between EACA dose and the percentage change in
      plasma alpha 2-A activity. In a few patients receiving prednisone plus EACA
      regimen, side effects that included purulent rhinitis, pharyngitis, increases in
      body temperature, loose stools, and an approximately 20% to 30% decrease in
      systolic and diastolic arterial blood pressure were observed. Thus, although the
      prednisone plus EACA treatment regimen seems to offer new therapeutic
      possibilities in some patients with NS, it should not be used in acute phase of
      the disease.

PMID- 11304664
TI  - Interspecies scaling of maximum tolerated dose of anticancer drugs: relevance to
      starting dose for phase I clinical trials.
AB  - This analysis was carried out to compare the predictive performance of two
      different approaches of allometry for the prediction of maximum tolerated dose
      (MTD) in humans from animal data. The two approaches used to predict MTD in
      humans in this analysis were (1) the use of a fixed exponent of 0.75 and the
      LD(10) in mice and (2) the use of the LD(10) or MTD data from at least three
      animal species (interspecies scaling). Twenty-five anticancer drugs were taken
      from the literature and used in this analysis. The results of the study indicate
      that MTD can be predicted more accurately using interspecies scaling than using a
      fixed exponent of 0.75. Incorporation of a correction factor known as mean life
      span potential can also be used for the improved prediction of MTD for some
      drugs. One third of the predicted MTD from interspecies scaling can be used as a
      starting dose in humans. This approach will save time and avoid many unnecessary
      steps in attaining MTD in humans.

PMID- 11304665
TI  - Influence of electrolyte abnormalities on interlead variability of ventricular
      repolarization times in 12-lead electrocardiography.
AB  - Increased QT dispersion (QT(d)) has been associated with increased risk for
      ventricular arrhythmias. Pathologic extracellular electrolyte concentrations may
      result in ventricular arrhythmias. The aim of this study was to evaluate the
      effect of electrolyte abnormalities on QT(d). Ten consecutive patients with
      isolated electrolyte abnormalities were selected for each of the following
      groups: hypokalemia, hyperkalemia, hypercalcemia, hypocalcemia, hypomagnesemia,
      and normal controls. Standard 12-lead electrocardiography was performed for each
      patient and average QT, JT, and RR intervals were calculated for each lead.
      Dispersion of QT, JT (JT(d)), and QTc (QTc(d)) intervals were calculated as the
      range between the longest and shortest measurements. Compared with controls, only
      patients with hypokalemia had a greater QT(d) (115 +/- 31 vs. 49 +/- 15 ms),
      JT(d) (116 +/- 34 vs. 52 +/- 12 ms), and QTc(d) (141 +/- 40 vs. 58 +/- 1 ms), (P
      < 0.05). In an experimental substudy, seven rats were maintained on K(+) and
      seven on Mg(2+)-free diet followed by normal diet. Experimental hypokalemia
      significantly increased QT(d) (10 +/- 4 to 37 +/- 7 ms), and QTc(d) (32 +/- 6 to
      79 +/- 27 ms) (P < 0.05), whereas hypomagnesemia did not. Restoration of serum
      potassium resulted in normalization of dispersion (QT(d), 14 +/- 2; QTc(d), 34 +/
      6 ms). Hypokalemia increases the dispersion of ventricular repolarization that
      may be responsible for arrhythmias. Even though hyperkalemia, hypocalcemia, and
      hypercalcemia are known to affect ventricular repolarization, our study shows
      that they are not associated with increased dispersion.

PMID- 11304666
TI  - Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 1:
      the older drugs.
AB  - Rheumatoid arthritis is the paradigmatic immune-mediated inflammatory arthropathy
      and may be of comparatively recent, New World origin. Apart from the symptom
      relieving nonsteroidal anti-inflammatory drugs, whose natural congeners have been
      in use since antiquity for musculoskeletal pain and inflammation, only a dozen
      drugs or drug classes--the disease-modifying antirheumatic drugs--are currently
      in common use in rheumatoid arthritis. Development of these drugs has been a
      notable achievement of the 20th century. Some were developed serendipitously
      (glucocorticoids, antimalarials), some were the product of faulty reasoning
      (gold, D-penicillamine), and others were applied for plausible reasons but whose
      mechanism remains unproven (sulfasalazine, methotrexate, minocycline). A minority
      were originally applied on the basis of actions that remain germane to the
      pathophysiology of rheumatoid arthritis as currently understood (azathioprine,
      cyclosporine, leflunomide, infliximab, etanercept). Among the latter are the more
      recently introduced and effective agents. The practical use of these drugs is
      determined by efficacy-toxicity considerations, which have also driven the recent
      development of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory
      drugs.

PMID- 11304669
TI  - DNA recognition of a 24-mer peptide derived from RecA protein.
AB  - A novel 24-residue peptide (L2-G), Ile-Arg-Met-Lys-Ile-Gly-Val-Met-Phe-Gly-Asn
      Pro-Glu-Thr-Thr-Thr-Gly-Gly-Asn-Ala-Leu-Lys-Phe-Tyr, derived from RecA can
      discriminate a single-stranded DNA (ssDNA) from a double-stranded DNA (dsDNA) and
      a new developed support with this peptide recognizes not dsDNA but ssDNA. The 24
      mer peptide with L2 and helix G amino acids of Escherichia coli RecA protein
      showed the ssDNA binding property with more than 1000 times affinity difference
      for the dsDNA. However, truncated 15-mer peptide showed no ssDNA binding
      activity. In the ssDNA binding, L2-G changed its conformation with the
      perturbation of an alpha-helix structure. The ssDNA binding and the DNA
      discrimination property of this peptide were due to almost all L2 and helix G
      amino acids, respectively. This result is useful to design synthetic peptides as
      functional materials for DNA recognition.

PMID- 11304670
TI  - Structural features of linear (alphaMe)Val-based peptides in solution by
      photophysical and theoretical conformational studies.
AB  - In continuation of our studies on the determination of the structural features of
      functionalized peptides in solution by combining time-resolved fluorescence data
      and molecular mechanics results, the conformational features of a series of
      linear, L-(alphaMe)Val-based peptides have been investigated in methanol. These
      foldamers have the general formula F[(alphaMe)Val](r)-T-[(alphaMe)Val](2)NHtBu,
      where (alphaMe)Val = C(alpha)-methylvaline and r = 0-3, while F [= fluoren-9
      ylmethoxycarbonyl (Fmoc)] and T [= 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino
      carboxylic (Toac)] are a fluorophoric N(alpha)-protecting group and a nitroxide
      based alpha-amino acid quencher, respectively. According to ir and CD spectra,
      the longest term of the series (r = 3) attains a 3(10)-helical structure, while
      the other peptides populate an intramolecularly H-bonded, 3(10)-helix-like
      conformation affected by dynamic helical distortions, which are enhanced by the
      shortness of the backbone chain. Such distortions are reflected in both the
      energy of the stretching mode and the molar extinction coefficient of the H
      bonded N-H groups, the former being higher and the latter smaller than those of a
      stable 3(10)-helix. Steady-state and time-resolved fluorescence measurements in
      methanol show a strong quenching of Fmoc by the Toac residue, located at
      different helix positions, depending on the r value. Comparison of quenching
      efficiencies and lifetime preexponents with those theoretically obtained from the
      deepest energy minimum conformers, assuming a Forster mechanism, is satisfactory.
      The computed structures exhibit a rather compact arrangement, which accounts for
      the few sterically favored conformations for each peptide, in full agreement with
      the time-resolved fluorescence data. Orientational effects between the probes
      must be taken into account for a correct interpretation of the fluorescence decay
      results, implying that interconversion among conformational substates involving
      the probes is slower than the energy transfer rate.

PMID- 11304671
TI  - Collagen model peptides: Sequence dependence of triple-helix stability.
AB  - The triple helix is a specialized protein motif, found in all collagens as well
      as in noncollagenous proteins involved in host defense. Peptides will adopt a
      triple-helical conformation if the sequence contains its characteristic features
      of Gly as every third residue and a high content of Pro and Hyp residues. Such
      model peptides have proved amenable to structural studies by x-ray
      crystallography and NMR spectroscopy, suitable for thermodynamic and kinetic
      analysis, and a valuable tool in characterizing the binding activities of the
      collagen triple helix. A systematic approach to understanding the amino acid
      sequence dependence of the collagen triple helix has been initiated, based on a
      set of host-guest peptides of the form, (Gly-Pro-Hyp)(3)-Gly-X-Y-(Gly-Pro
      Hyp)(4). Comparison of their thermal stabilities has led to a propensity scale
      for the X and Y positions, and the additivity of contributions of individual
      residues is now under investigation. The local and global stability of the
      collagen triple helix is normally modulated by the residues in the X and Y
      positions, with every third position occupied by Gly in fibril-forming collagens.
      However, in collagen diseases, such as osteogenesis imperfecta, a single Gly may
      be substituted by another residue. Host-guest studies where the Gly is replaced
      by various amino acids suggest that the identity of the residue in the Gly
      position affects the degree of destabilization and the clinical severity of the
      disease.

PMID- 11304672
TI  - Surface grafting onto template-assembled synthetic protein scaffolds in molecular
      recognition.
AB  - Creating functional biological molecules de novo requires a detailed
      understanding of the intimate relationship between primary sequence, folding
      mechanism, and packing topology, and remains up to now a most challenging goal in
      protein design and mimicry. As a consequence, the use of well-defined robust
      macromolecules as scaffolds for the introduction of function by grafting surface
      residues has become a major objective in protein engineering and de novo design.
      In this article, the concept of scaffolds is demonstrated on some selected
      examples, illustrating that novel types of functional molecules can be generated.
      Reengineered proteins and, most notably, de novo designed peptide scaffolds
      exhibiting molecular function, are ideal tools for structure-function studies and
      as leads in drug design.

PMID- 11304673
TI  - Incorporation of artificial receptors into a protein/peptide surface: a strategy
      for on/off type of switching of semisynthetic enzymes.
AB  - Recent developments in new bioorganic methodologies have greatly facilitated the
      site-specific incorporation of non-natural amino acids into the protein
      framework. It is now desirable for chemists to explore promising concepts based
      on chemistry for regulation and extension of functions of naturally occurring
      enzymes using non-natural molecules, in order to promote the new trends in
      protein/enzyme engineering. This article demonstrates that the concepts of host
      guest (or supramolecular) chemistry, which have been developed over the last few
      decades, provide powerful tools for the artificial control of the functions of
      native proteins and enzymes.

PMID- 11304674
TI  - Artificial peptides with unnatural components designed for materializing protein
      function.
AB  - In order to design functional peptides, we employed two strategies. The first one
      is to incorporate rigid unnatural amino acids into peptides to make the peptide
      backbone rigid. Functions were expected to appear through the conformational
      control by the strategy. A series of cyclic peptides constituted of alternating
      natural amino acids and 3-aminobenzoic acid, used as an unnatural amino acid,
      were synthesized. These cyclic peptides were found to function as strong binders
      for phosphomonoester, catalysts for ester hydrolysis, and/or ion channels. The
      second strategy is to conjugate peptides with unnatural and inherently functional
      molecules. Following this strategy, oligo(L-leucine)- or oligo(L-phenylalanine)
      modified ruthenium tris(bipyridine) complexes were synthesized. Distance
      dependence of the photoinduced electron transfer from the ruthenium complexes and
      the function as sensors for phosphate anion (H(2)PO(-)(4)) are discussed.

PMID- 11304675
TI  - Electron spin resonance of TOAC labeled peptides: folding transitions and high
      frequency spectroscopy.
AB  - The unnatural, conformationally constrained nitroxide amino acid TOAC (2,2,6,6
      tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) stabilizes helical
      structure and provides a means for studying rigidly spin labeled peptides by
      electron spin resonance (ESR). Two new directions in TOAC research are described.
      The first investigates intermediates formed during alpha-helix unfolding. Double
      TOAC labeled alpha-helical peptides were unfolded at low temperature in aqueous
      solution with increasing concentrations of guanidine hydrochloride. Comparison of
      ESR spectra from two doubly labeled peptides suggests that 3(10)-helix emerges as
      an intermediate. The second research direction involves the use of high frequency
      ESR (140 GHz) at low temperature to assess dipolar couplings and, hence,
      distances between TOAC pairs in a series of 3(10)-helical peptides. Preliminary
      simulations suggest that high frequency ESR is able to extract correct distances
      between 6 and 11 A. In addition, the spectra appear to be very sensitive to the
      relative orientation of the TOAC labels.

PMID- 11304676
TI  - Interaction between TOAC free radical and photoexcited triplet chromophores
      linked to peptide templates.
AB  - The intramolecular quenching of photoexcited triplet states by free radicals
      linked to peptide templates was studied by time-resolved electron paramagnetic
      resonance (EPR) with pulsed laser excitation. The systems investigated are 3(10)
      helix forming peptides, having in the amino acid sequence the free radical
      2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) and a
      triplet precursor, such as Bin, Bpa, or Trp, incorporated at different relative
      positions. Upon interaction with the excited triplet the TOAC radical spin
      sublevel populations assume values that differ from the Boltzmann equilibrium
      values. This spin polarization effect produces EPR lines in emission whose time
      evolution reflects the triplet quenching rate. In particular, in a series of
      peptides labeled with Bpa and TOAC at successive positions in the 3(10)-helix,
      radical-triplet interaction was observed in all cases. However, for the peptide
      where Bpa and TOAC are at positions 2 and 4 the rate of triplet quenching is
      lower than for the other peptides in the series. In addition, the radical-excited
      triplet complex in the quartet spin state was observed in a peptide containing
      fullerene (C(60)) as a triplet precursor and TOAC.

PMID- 11304677
TI  - An azacrown-functionalized peptide as a metal ion based catalyst for the cleavage
      of a RNA-model substrate.
AB  - The previously synthesized, terminally blocked heptapeptide Ac-Aib-ATANP-Aib-Aib
      ATANP-Aib-Aib-OMe (1a), where ATANP is (S)-2-amino-3-[1-(1,4,7
      triazacyclononane)]propanoic acid and Aib is alpha-aminoisobutyric acid, which is
      soluble in neutral water where it largely adopts a 3(10)-helical conformation,
      has been studied, as bimetallic complex [metal ions: Cu(II), Ni(II), Zn(II)], for
      the transphosphorylation catalysis of the RNA-model substrate 2-(hydroxypropyl)-p
      nitrophenyl phosphate (HPNP). A detailed analysis was carried out with the Zn(II)
      dinuclear complex. Comparison with the mononuclear Zn(II) complex with 1,4,7
      triazacyclononane (3) points to cooperativity between the two Zn(II) ions in the
      process catalyzed by 1a-2Zn(II). On the contrary, the dinuclear Zn(II) complex of
      dipeptide Ac-(ATANP)(2)-OMe (2), lacking any ordered conformation, is less active
      than 3-Zn(II). The kinetic analysis suggests the following: (a) the peptide is
      conformationally very robust and does not loose activity up to 50 degrees C; (b)
      the substrate binds to the peptide-Zn(II) complex, although not all modes of
      complexation allow us to take advantage of the cooperativity between the two
      metal centers. The maximum rate acceleration estimated at pH 7 for the fully
      bound substrate is ca. 200-fold compared with the uncatalyzed process.

PMID- 11304678
TI  - Pharmacological and endogenous progestins induce vascular endothelial growth
      factor expression in human breast cancer cells.
AB  - Tumor expansion is dependent on angiogenesis, which is regulated by peptide
      growth factors of which vascular endothelial growth factor (VEGF) is one of the
      most selective and potent. VEGF expression is regulated by steroid hormones in a
      number of systems, including T47-D human breast cancer cells in which VEGF
      protein levels are elevated by progestins. In the present study, we investigated
      the effect of progestins on VEGF mRNA levels in human breast cancer cells. For
      these experiments, T47-D cells were exposed to progestins, RNA was prepared for
      measurement of VEGF transcript levels by Northern blot analysis and VEGF protein
      in the cell culture media was measured by enzyme-linked immunosorbent assay.
      Basal expression of VEGF mRNA is low in these cells, and is rapidly induced
      following exposure to progestins, reaching a maximum induction of 2- to 5-fold
      between 3 and 6 hr after hormone addition. This induction was inhibited by the
      antiprogestin RU-486 indicating that it is progesterone receptor (PR) dependent.
      Transcripts for VEGF165 and VEGF121 were the two major spliced forms of VEGF mRNA
      that were detected by reverse transcription-polymerase chain reaction in basal
      and progestin-stimulated T47-D cells. Maximum induction of VEGF mRNA was achieved
      with 10(-8) M progesterone, and induction was hormone specific, as estrogens,
      glucocorticoids, and androgens were without effect. Actinomycin D completely
      abolished the induction of VEGF transcript levels by progestins, suggesting that
      this response involves de novo mRNA synthesis, but puromycin did not inhibit
      induction, suggesting that this effect does not require protein synthesis. This
      report demonstrates that progestins stimulate VEGF mRNA levels and raises the
      possibility that anti-progestins may be useful to inhibit proliferation and
      metastasis in some human breast cancers by blocking VEGF production.

PMID- 11304679
TI  - c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.
AB  - Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial
      response to chemotherapy. It is therefore important to identify molecular markers
      that influence survival as potential new therapeutic targets. In our study,
      expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues
      of 107 consecutive newly diagnosed patients with primary SCLC was quantified
      using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A
      clear-cut positive expression of c-erbB-2 was observed in 13% of patients.
      Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p =
      0.014) when a proportional-hazard model was adjusted to stage (limited vs.
      extensive disease) and performance status (WHO I-IV), the most relevant clinical
      parameters. Similarly, a significant association between c-erbB-2 and survival
      was obtained if a larger number of clinical parameters were included into the
      analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase
      (LDH), neuron-specific enolase (NSE), gender and age (p = 0.033). Interestingly,
      c-erbB-2 expression was more relevant for patients with advanced tumors. In the
      subgroup of patients with bad performance status (WHO II-IV), median survival of
      patients with undetectable c-erbB-2 expression was 274 days compared with only 23
      days for patients with clear-cut positive c-erbB-2 immunohistochemistry (p =
      0.0031; log-rank test). Similar results were obtained for patients with extensive
      disease (p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all
      comparisons). In contrast, c-erbB-2 expression was not associated with survival
      in patients with limited disease (p = 0.97), low TNM stages (p > 0.56, all
      comparisons) and good performance status (p = 0.97). In conclusion, c-erbB-2 is
      expressed in more than 10% of SCLC. Expression of c-erbB-2 is an independent
      prognostic factor of survival. The effect of c-erbB-2 expression seems to become
      more important in advanced stages of the disease. Since c-erbB-2 is a
      therapeutical target in other types of cancer, further studies to identify the
      role of c-erbB-2 in SCLC are clearly warranted.

PMID- 11304680
TI  - Herceptest: HER2 expression and gene amplification in non-small cell lung cancer.
AB  - HER2 is an erbB/HER type 1 tyrosine kinase receptor that is frequently over
      expressed in malignant epithelial tumours. Herceptin, a humanised mouse
      monoclonal antibody to HER2, is proven therapeutically in the management of
      metastatic breast cancer, significantly prolonging survival when combined with
      cytotoxic chemotherapeutic agents. Immunohistochemical studies suggest that non
      small-cell lung cancer (NSCLC) tumours may over-express HER2. Our aim was to
      evaluate HER2 gene amplification and semi-quantitative immuno-expression in
      NSCLC. A total of 344 NSCLC cases were immunostained for HER2 expression in 2
      centres using the HercepTest. Fluorescence in situ hybridisation (FISH) analysis
      for HER2 gene amplification was performed on most positive cases and a subset of
      negative cases. Fifteen cases (4.3%) demonstrated 2+ or 3+ membranous HER2 immuno
      expression. There was no correlation between immuno-expression and tumour
      histology or grade. Tumours from higher-stage disease were more often HercepTest
      positive (p < 0.001). All 4 HercepTest 3+ cases demonstrated gene amplification.
      One of the 5 2+ cases tested for gene amplification showed areas of borderline
      amplification and areas of polyploidy. None of the 19 HercepTest-negative cases
      demonstrated gene amplification or polyploidy (p < 0.001). Gene amplification was
      demonstrated in all HercepTest 3+ scoring NSCLC cases. Unlike breast cancer, gene
      amplification and HER2 protein over-expression assessed by the HercepTest
      appeared to be uncommon in NSCLC. Herceptin may therefore target only a small
      proportion of NSCLC tumours and be of limited clinical value in this disease,
      particularly in the adjuvant setting.

PMID- 11304681
TI  - Effects of human fibroblasts from myelometaplasic and non-myelometaplasic
      hematopoietic tissues on CD34+ stem cells.
AB  - Fibroblasts demonstrate different phenotypes and functions according to the
      tissue of origin and its physiopathologic state. We previously showed that
      fibroblasts isolated in culture from myelometaplasic (MM) spleen differed
      phenotypically from fibroblasts from normal bone marrow (BM). We compared the
      influence of each type of fibroblasts on the behavior of CD34+ stem cells.
      Expansion of nucleated cells was observed when blood CD34+ cells were co-cultured
      for 3 weeks with MM spleen-derived fibroblasts in monolayers. Myeloid cell
      differentiation was also observed as indicated by a decline in CD34+ cells and
      increases in CD14+, CD15+ and CD41+ cells. This myeloid differentiation was
      enhanced in the presence of MM spleen compared with normal BM-derived
      fibroblasts. Similarly, proliferation and differentiation of BM CD34+ cells was
      better in the presence of BM rather than MM spleen-derived fibroblasts. In
      addition, fibroblasts from MM spleen also induced a differentiation of CD56+
      natural killer (NK) cells whereas BM-derived fibroblasts did not. Overall, the
      data indicate that cultured fibroblasts from diseased tissue have distinct growth
      and differentiation regulatory characteristics. They also suggest a role for
      these cells in hematopoietic disorders.

PMID- 11304682
TI  - A novel orthotopic implantation model of human esophageal carcinoma in nude rats:
      CD44H mediates cancer cell invasion in vitro and in vivo.
AB  - A new orthotopic esophageal cancer model was developed by implanting fragments of
      xenografts of T.T human esophageal squamous carcinoma cells into the cervical
      esophagus of athymic rats. The rats had symptoms analogous to the human clinical
      course such as respiratory distress, dysphagia, vomiting of blood, or Horner
      syndrome, followed by death resulting from suffocation. Microscopic metastases of
      lymph node were observed around the tumor in 3 of 18 rats. A new cell line (T.T
      1) was established from these metastases. Flow cytometry showed that T.T-1 and
      T.T parental cells had nearly the same surface levels of beta1-integrin, alpha2
      integrin, alpha3-integrin and E-cadherin, and no expression of CD44v3, CD44v6 and
      alpha5-integrin. T.T-1 cells had a higher level of CD44H, however, and a greater
      binding efficiency to the extracellular matrix components; laminin, type IV
      collagen, hyaluronic acid, and fibronectin than T.T cells. Anti-CD44H antibody
      significantly decreased the binding efficiency of T.T-1 cells. T.T-1 cells were
      also significantly more invasive than T.T cells through all the extracellular
      matrix components except hyaluronic acid. After orthotopic implantation
      histological examination showed that T.T-1 tumors invaded beyond the esophageal
      mucosa and tracheal muscle layer and obstructed the esophagus and trachea. No
      invasion was observed with T.T tumors. Rats with T.T-1 or T.T tumors survived an
      average of 32.0 and 50.7 days, respectively (p < 0.01). In addition T.T-1 tumors
      expressed higher levels of CD44H mRNA than T.T tumors. In summary, our newly
      developed orthotopic implantation model is a valid model of esophageal cancer
      because it followed the same clinical course experienced by humans. Moreover,
      using cells derived from this model, we were able to demonstrate that CD44H is
      involved in esophageal cancer cell invasion.

PMID- 11304683
TI  - Dedifferentiation of serous ovarian cancer from cystic to solid tumors is
      associated with increased expression of mRNA for urokinase plasminogen activator
      (uPA), its receptor (uPAR) and its inhibitor (PAI-1).
AB  - The plasminogen activating system is involved in tumor growth and metastasis by
      degradation of extracellular matrix, and modulation of cell adhesion and
      migration. Benign and well-differentiated malignant ovarian tumors present as
      cystic lesions with preserved glandular morphology, whereas poorly differentiated
      tumors and metastases are solid with characteristic absence of glandular
      morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its
      receptor (uPAR), and inhibitor (PAI-1) in serous ovarian tumors by in situ
      hybridization and by densitometric scanning of Northern blots prepared from
      tissue extracts. The mRNA expressing cells in the in situ hybridization sections
      were evaluated and counted by two different observers. The number of mRNA
      expressing cells for uPA, uPAR and PAI-1 were all significantly increased in
      solid as compared with cystic malignant tumors. The increased expression of all
      three mRNA species was mainly located in the stroma of poorly differentiated
      tumors and metastases. Apart from being expressed in the stroma of these tumors,
      uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial
      boarder. In addition, the tumor tissue content of uPA, uPAR and PAI-1 mRNAs as
      measured by Northern blots were higher in the solid as compared with the cystic
      tumors. Increased expression of uPA, uPAR and PAI-1 genes in the solid tumors
      suggest a correlation with a more aggressive phenotype.

PMID- 11304684
TI  - Involvement of the neurotensin receptor subtype NTR3 in the growth effect of
      neurotensin on cancer cell lines.
AB  - The expression of the 3 currently known neurotensin receptors was studied in
      human cancer cells of prostatic, colonic or pancreatic origin by means of RT-PCR
      analysis and binding experiments. All the cells selected for this work have been
      shown to exhibit a growth response to neurotensin. We found that the 7
      transmembrane domain, levocabastine insensitive receptor (NTR1) is expressed in
      most but not all of the cells studied whereas the 7 transmembrane domain,
      levocabastine sensitive receptor (NTR2) is present in none of these cells. The
      100 kDa-type I neurotensin receptor (NTR3) is expressed in all the cells assayed.
      Moreover, we demonstrated that neurotensin can stimulate the growth of CHO cells
      stably transfected with the NTR3. Taken together, our results strongly suggest
      that the NTR3 subtype could be involved in the growth response of human cancer
      cells to neurotensin.

PMID- 11304685
TI  - An FGF-binding protein (FGF-BP) exerts its biological function by parallel
      paracrine stimulation of tumor cell and endothelial cell proliferation through
      FGF-2 release.
AB  - Fibroblast growth factors FGF-1 (aFGF) and FGF-2 (bFGF) are found in most
      embryonic and adult normal and tumor tissues, where they are immobilized in the
      extracellular matrix (ECM). Mobilization of these FGFs is part of a tightly
      controlled process resulting in the activation of high-affinity FGF receptors.
      Recently, we have shown that a secreted FGF-binding protein (FGF-BP) binds non
      covalently to FGF-2 and is able to release it from the ECM. This process of
      growth factor bioactivation seems to play a pivotal role in the growth of
      squamous cell carcinomas, especially through induction of tumor angiogenesis.
      Since previous studies provided only indirect evidence for the proposed mechanism
      of FGF-BP-mediated FGF-2 release, we decided to use recombinant purified FGF-BP
      to study further the underlying mechanism of FGF-BP action. Here we show that FGF
      BP is able to bind directly to FGF-2 without additional cofactors and to exhibit
      bioactivity. The purified recombinant FGF-BP stimulates tumor cell growth as well
      as endothelial cell growth and chemotaxis, indicating a dual growth-supporting
      role of FGF-BP in tumors. We show that this paracrine FGF-BP effect is dependent
      on endogenously expressed FGF-2, since it can be completely blocked by anti-FGF-2
      antibodies. In tumor xenografts and in tumor cells, we detected a pattern of
      specific FGF-BP-immunoreactive high molecular weight forms, which presumably
      represent stable covalent complexes of FGF-BP and show marked differences in
      their occurrence in different tumors and in their heparin binding affinity. By
      providing further insight into the mechanism of FGF-BP action, our results
      emphasize the relevance of FGF-BP and of FGF-2 in tumor growth.

PMID- 11304686
TI  - Apoptosis induced by arsenic trioxide in leukemia U937 cells is dependent on
      activation of p38, inactivation of ERK and the Ca2+-dependent production of
      superoxide.
AB  - The mechanism of the induction of apoptosis by arsenic trioxide (As2O3), which
      was demonstrated recently to be an effective inducer of apoptosis in patients
      with leukemia, was examined in detail in human leukemia U937 cells. Upon
      treatment of U937 cells with 50 microM of As2O3, complete inactivation of the
      kinases ERK1 and ERK2 was detected within 30 min. p38 was activated within 3 hr,
      and the maximum activity was detected at 6 hr, when DNA fragmentation remained
      undetectable. Experiments with transfected cells that expressed constitutively
      activated MEK1 and a specific inhibitor of p38 also suggested that inactivation
      of ERKs and activation of p38 might be associated with the induction of apoptosis
      by As2O3. In contrast to the inactivation of ERKs and the activation of p38,
      activation of JNK by As2O3 appeared to protect cells against the induction of
      apoptosis. Treatment of U937 cells with As2O3 also caused the Ca2+-dependent
      production of superoxide and intracellular acidification and a decrease in the
      mitochondrial membrane potential at the early stages of induction of apoptosis by
      As2O3. These changes preceded the release of cytochrome c from mitochondria and
      the activation of caspase-3. It should be possible to exploit the unusual
      characteristics of the mechanism of induction of apoptosis by As2O3 in U937 cells
      by making use of synergistic effects of this compound with other inducers of
      apoptosis.

PMID- 11304687
TI  - Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces
      invasion through episialin-mediated neutralization of E-cadherin in human mammary
      MCF-7 cells in vitro.
AB  - 1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OMe) is an analogue of the
      naturally occurring 2-lysophosphatidylcholine belonging to the class of antitumor
      lipids. Previously, we demonstrated that ET-18-OMe modulates cell-cell adhesion
      of human breast cancer MCF-7 cells. In the present study, we tested the effect of
      ET-18-OMe on adhesion, invasion and localisation of episialin and E-cadherin in
      MCF-7/AZ cells expressing a functional E-cadherin/catenin complex. The MCF-7/6
      human breast cancer cells were used as negative control since their E
      cadherin/catenin complex is functional in cells grown on solid substrate but not
      in suspension. The function of E-cadherin, a calcium-dependent transmembrane cell
      cell adhesion and signal-transducing molecule, is disturbed in invasive cancers
      by mutation, loss of mRNA stability, proteolytic degradation, tyrosine
      phosphorylation of associated proteins and large cell-associated proteoglycans or
      mucin-like molecules such as episialin. Episialin, also called MUC1, is an anti
      adhesion molecule that by its large number of glycosylated tandem repeats can
      sterically hinder the adhesive properties of other glycoproteins. ET-18-OMe
      inhibited the E-cadherin functions of MCF-7/AZ cells as measured by inhibition of
      fast and slow aggregation and by the induction of collagen invasion. These
      effects were enhanced by MB2, an antibody against E-cadherin and blocked by
      monoclonal antibodies (MAbs) 214D4 or M8 against episialin. ET-18-OMe had no
      influence on tyrosine phosphorylation of beta-catenin and the E-cadherin/catenin
      complex remained intact. Transcription, translation, protein turnover and cell
      surface localisation of episialin were not altered. ET-18-OMe induced finger-like
      extensions with clustering of episialin together with E-cadherin and
      carcinoembryonic antigen but not with occludin. In cells in suspension, ET-18-OMe
      caused a shift in the flow-cytometric profile of episialin toward a lower
      intensity for MCF-7/AZ cells. In contrast with MCF-7/AZ cells, the adhesion
      deficient and noninvasive MCF-7/6 cells showed neither morphotypic changes nor
      induction of aggregation nor invasion in collagen I upon treatment with ET-18
      OMe. Co-localisation of episialin with E-cadherin was rarely observed. We
      conclude that in the human breast cancer cells MCF-7/AZ, E-cadherin and episialin
      are key molecular players in the regulation of promotion and suppression of cell
      cell adhesion and invasion.

PMID- 11304688
TI  - Integration of adeno-associated virus 2 DNA in human MKR melanoma cells induces a
      peptide with oncosuppressive properties.
AB  - Integration of adeno-associated virus type 2 (AAV2) DNA into the genome of the
      human MKr melanoma cell line grossly alters the cellular phenotype of these
      cells. Cultures derived from AAV DNA-harboring single cells share various
      similarities with normal cells in culture, and a considerable number of clones
      show signs of cellular senescence and terminal differentiation. Medium
      conditioned by such terminally differentiating cells contains a small cytokine
      like factor (AAV-induced factor [AIF]). The factor was characterized as peptide,
      which influences cell adhesion and appears to exist in forms of different
      activity connected by a trypsin-like cleavage site. It modulates cell growth in
      opposite ways: proliferation of tumor-derived cells is inhibited and fibroblasts
      are stimulated. The observations suggest that integration of AAV may result in
      cytokine induction and thus can indirectly affect growth of distant AAV-free
      target cells in a paracrine or endocrine manner. This is of interest with regard
      to anti-oncogenic properties of AAV and may also imply the possibility of AAV
      pathogenicity.

PMID- 11304689
TI  - Somatostatin inhibits the production of vascular endothelial growth factor in
      human glioma cells.
AB  - In various cell types, the neuro- and endocrine peptide somatostatin induces
      inhibitory and anti-secretory effects. Since somatostatin receptors, especially
      of the subtype sst2A, are constantly over-expressed in gliomas, we investigated
      the influence of somatostatin and the receptor subtype-selective peptide/non
      peptide agonists octreotide and L-054,522 on the secretion of the most important
      angiogenesis factor produced by gliomas, vascular endothelial growth factor
      (VEGF). Cultivated cells from solid human gliomas of different stages and glioma
      cell lines secreted variable amounts of VEGF, which could be lowered to 25% to
      80% by co-incubation with somatostatin or sst2-selective agonists (octreotide and
      L-054,522). These effects were dose-dependent at nanomolar concentrations.
      Stimulation with different growth factors (EGF, bFGF) or hypoxia considerably
      increased VEGF production over basal levels. Growth factor-induced VEGF synthesis
      could be suppressed to <50% by co-incubation with somatostatin or an sst2
      selective agonist; this was less pronounced in hypoxia-induced VEGF synthesis.
      The effects were detected at the protein and mRNA levels. These experiments
      indicate a potent anti-secretory action of somatostatin or sst2 agonists on human
      glioma cells that may be useful for inhibiting angiogenesis in these tumors.

PMID- 11304690
TI  - Analysis of human meningiomas for aberrations of the MADH2, MADH4, APM-1 and DCC
      tumor suppressor genes on the long arm of chromosome 18.
AB  - We have previously reported that losses of genomic material from the long arm of
      chromosome 18 are frequent in atypical and anaplastic meningiomas but rare in
      benign meningiomas. In the present study, we have investigated a series of 37
      meningiomas for mutation and expression of 4 tumor suppressor genes (MADH2,
      MADH4, APM-1 and DCC) located at 18q21. Comparative genomic hybridization or loss
      of heterozygosity analysis showed losses on chromosome 18 that included sequences
      from 18q21 in 15 of 37 tumors. Mutation analysis of APM-1 revealed a missense
      mutation (c. 1819G>A: G607S) in 1 atypical meningioma. None of the tumors showed
      mutations of MADH2 and MADH4 or loss of detectable transcripts from MADH2, MADH4,
      APM-1 and DCC. In contrast to human brain tissue, normal leptomeninges and
      meningiomas showed preferential expression of a DCC splice variant lacking 60
      base pairs from exon 17. Taken together, our data do not support a significant
      role for MADH2, MADH4, APM-1 and DCC alterations in the pathogenesis of
      meningiomas. The targeted gene that is inactivated in most meningiomas with 18q
      losses remains to be identified.

PMID- 11304691
TI  - Microsatellite instability in squamous cell carcinoma of head and neck from the
      Indian patient population.
AB  - Genomic instability in simple repeated sequences has been observed in several
      human cancers. We have analyzed 50 squamous cell carcinomas of the head and neck
      (SCCHN) and 5 pre-malignant severe dysplastic tissues from Indian patient
      populations for microsatellite instability in 18 different loci spread over eight
      different chromosomes. Among the tumors analyzed, 45% exhibited instability at
      two or more loci, and 15% exhibited instability at 40% of the markers tested.
      Similar analysis of SCCHN tumors from other populations (British, American and
      French) showed much less frequency of instability. SCCHN tumors in the present
      study did not show any instability in the mononucleotide repeat sequences. There
      is also a clear distinction in the nature of the instability in these tumors in
      comparison with colorectal tumors. These results suggest that the underlying
      mechanism generating this type of instability is different from those reported
      for colorectal tumors.

PMID- 11304692
TI  - DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder
      cancer in a case-control study.
AB  - Individuals differ widely in their ability to repair DNA damage, and DNA-repair
      deficiency may be involved in modulating cancer risk. In a case-control study of
      124 bladder-cancer patients and 85 hospital controls (urological and non
      urological), 3 DNA polymorphisms localized in 3 genes of different repair
      pathways (XRCC1-Arg399Gln, exon 10; XRCC3-Thr241Met, exon 7; XPD-Lys751Gln, exon
      23) have been analyzed. Results were correlated with DNA damage measured as (32)P
      post-labeling bulky DNA adducts in white blood cells from peripheral blood.
      Genotyping was performed by PCR-RFLP analysis, and allele frequencies in
      cases/controls were as follows: XRCC1-399Gln = 0.34/0.39, XRCC3-241Met =
      0.48/0.35 and XPD-751Gln = 0.42/0.42. Odds ratios (ORs) were significantly
      greater than 1 only for the XRCC3 (exon 7) variant, and they were consistent
      across the 2 control groups. XPD and XRCC1 appear to have no impact on the risk
      of bladder cancer. Indeed, the effect of XRCC3 was more evident in non-smokers
      [OR = 4.8, 95% confidence interval (CI) 1.1-21.2]. XRCC3 apparently interacted
      with the N-acetyltransferase type 2 (NAT-2) genotype. The effect of XRCC3 was
      limited to the NAT-2 slow genotype (OR = 3.4, 95% CI 1.5-7.9), suggesting that
      XRCC3 might be involved in a common repair pathway of bulky DNA adducts. In
      addition, the risk of having DNA adduct levels above the median was higher in NAT
      2 slow acetylators, homozygotes for the XRCC3-241Met variant allele (OR = 14.6,
      95% CI 1.5-138). However, any discussion of interactions should be considered
      preliminary because of the small numbers involved. Our results suggest that
      bladder-cancer risk can be genetically modulated by XRCC3, which may repair DNA
      cross-link lesions produced by aromatic amines and other environmental chemicals.

PMID- 11304693
TI  - Impairment of mammary lobular development induced by expression of TGFbeta1 under
      the control of WAP promoter does not suppress tumorigenesis in MMTV-infected
      transgenic mice.
AB  - It has previously been shown that transgenic female mice expressing TGFbeta1
      under control of regulatory elements of the whey-acidic protein (WAP) gene were
      unable to lactate. This was due to the increased apoptosis of the cells committed
      to the lobular-lactogenic phenotype. Our goal was to determine whether the
      expression of WAP-TGFbeta1 transgene could inhibit MMTV (mouse mammary tumor
      virus) tumorigenic activity in the mammary gland. It is well known that the
      infection with this virus produces focal hyperplastic secretory nodules (HANs)
      and, some variants can also induce ductal pregnancy-dependent lesions (plaques).
      In either case, MMTV infection leads ultimately to the appearance of malignant
      mammary tumors. The results shown herein demonstrate that TGFbeta1 expression in
      the secretory mammary epithelium does not suppress mammary tumorigenesis in MMTV
      infected mice. Although MMTV infected WAP-TGFbeta1 transgenic females displayed a
      strong impairment of lobule-alveolar development, carcinogenesis induced by any
      of the four MMTV variants used herein proceeded unabated. WAP-TGFbeta1 tumors
      that showed a strong expression at the WAP promoter, appeared later and grew more
      slowly than their wild-type counterparts. Transgenic females also had a lower
      incidence of HANs and plaques. Our study suggests that the epithelial target
      cells for tumorigenic mutations are probably progenitor cells that are not
      susceptible to the apoptotic effect of TGFbeta1. Alternatively, their daughters
      cells that display the secretory phenotype and could be more involved in the
      formation of premalignant lesions continue to die due to the expression of the
      transgene.

PMID- 11304694
TI  - Detection and enrichment of disseminated renal carcinoma cells from peripheral
      blood by immunomagnetic cell separation.
AB  - We have established an immunomagnetic separation procedure for the detection of
      circulating tumor cells in the peripheral blood based on the magnetic cell
      sorting (MACS) technique. In previous in vitro experiments, renal-cell carcinoma
      (RCC) cells were mixed with peripheral blood. In dilutions of 1:200 to 1:107
      tumor cells per mononuclear blood cells, an average recovery rate of 84% of tumor
      cells was determined. In our study, 104 peripheral blood samples from 59 renal
      carcinoma patients were analyzed. MACS resulted in significant depletion of
      leukocytes, permitting a search for tumor cells on just 1 slide. Analyzing 8 ml
      of peripheral blood per patient, 19/59 RCC patients carried disseminated tumor
      cells (32%) in the range of 1 to 38 cells (median 8). Interestingly, for the
      cytokeratin-positive (CK+) patient group, we found a correlation between tumor
      cell number and grading (G2 vs. G3) and an increased number of CK+ patients with
      advanced tumor stage. MACS appears to be an efficient technique to detect
      disseminated tumor cells in peripheral blood.

PMID- 11304695
TI  - Unique pattern of ET-743 activity in different cellular systems with defined
      deficiencies in DNA-repair pathways.
AB  - The cytotoxic activity of ecteinascidin 743 (ET-743), a natural product derived
      from the marine tunicate Ecteinascidia turbinata that exhibits potent anti-tumor
      activity in pre-clinical systems and promising activity in phase I and II
      clinical trials, was investigated in a number of cell systems with well-defined
      deficiencies in DNA-repair mechanisms. ET-743 binds to N2 of guanine in the minor
      groove, but its activity does not appear to be related to DNA-topoisomerase I
      poisoning as the drug is equally active in wild-type yeast and in yeast with a
      deletion in the DNA-topoisomerase I gene. Defects in the mismatch repair pathway,
      usually associated with increased resistance to methylating agents and cisplatin,
      did not affect the cytotoxic activity of ET-743. However, ET-743 did show
      decreased activity (from 2- to 8-fold) in nucleotide excision repair (NER)
      deficient cell lines compared to NER-proficient cell lines, from either hamsters
      or humans. Restoration of NER function sensitized cells to ET-743 treatment. The
      DNA double-strand-break repair pathway was also investigated using human
      glioblastoma cell lines MO59K and MO59J, respectively, proficient and deficient
      in DNA-dependent protein kinase (DNA-PK). ET-743 was more effective in cells
      lacking DNA-PK; moreover, pre-treatment of HCT-116 colon carcinoma cells with
      wortmannin, a potent inhibitor of DNA-PK, sensitized cells to ET-743. An increase
      in ET-743 sensitivity was also observed in ataxia telangiectasia-mutated cells.
      Our data strongly suggest that ET-743 has a unique mechanism of interaction with
      DNA.

PMID- 11304696
TI  - CD40-CD40 ligand (CD154) engagement is required but not sufficient for modulating
      MHC class I, ICAM-1 and Fas expression and proliferation of human non-small cell
      lung tumors.
AB  - To determine the possible functional significance of CD40 expression on human non
      small cell lung carcinomas and to assess the potential of CD40 as a therapeutic
      target, 18 lung tumor cell lines were established from biopsy tissues and were
      monitored for phenotypic changes on the cell surface and alterations in tumor
      cell proliferation after the ligation of CD40 with a trimeric fusion protein
      complex of CD40 ligand (CD40Lt). CD40 cross-linking resulted in up to a 6-fold
      increase in the surface expression of major histocompatibility complex (MHC)
      class I, Fas and intracellular adhesion molecule (ICAM)-1 in a subset of tumors
      expressing the highest levels of CD40. Suppression of tumor proliferation was
      seen after the ligation of CD40 on CD40Lt-responsive cell lines. The suppression
      was dose dependent, reversible and resulted from a delay of the tumor cells
      entering S-phase. No change in the cell phenotype or in proliferation were
      observed in CD40-negative tumors or in tumors expressing moderate-to-low levels
      of CD40 after incubation with CD40Lt. CD40-negative tumors transfected with the
      CD40 gene expressed high levels of CD40 on their surface, but were also
      unresponsive to CD40Lt cross-linking of CD40. Our data establish that CD40 is
      required (but not sufficient) for transducing a signal that results in phenotypic
      changes in human lung tumors and suppression in their proliferation. We conclude
      that CD40 on non-small cell lung tumors may represent a potential therapeutic
      target, but only on a subset of the CD40+ tumors.

PMID- 11304697
TI  - Protective effect of green tea on the risks of chronic gastritis and stomach
      cancer.
AB  - Despite the declining trend, stomach cancer remains the second most common cancer
      worldwide. We examined the role of green tea consumption on chronic gastritis and
      stomach cancer risks. A population-based case-control study was conducted in
      Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and
      433 healthy controls. Epidemiologic data were collected by standard questionnaire
      and odds ratios (OR) and 95% confidence intervals (CI) were estimated using
      logistic regression models in SAS. Inverse association was observed between green
      tea drinking and chronic gastritis and stomach cancer risks. After adjusting for
      age, gender, education, body mass index, pack-years of smoking and alcohol
      drinking, ORs of green tea drinking were 0.52 (95% CI: 0.29-0.94) and 0.49 (95%
      CI: 0.31-0.77) for stomach cancer and chronic gastritis, respectively. In
      addition, dose-response relationships were observed with years of green tea
      drinking in both diseases. The results provide further support on the protective
      effect of green tea against stomach cancer. This is the first time that green tea
      drinking was found to be protective against chronic gastritis, which may be of
      importance when designing intervention strategies for stomach cancer and its pre
      malignant lesions in the high-risk population.

PMID- 11304698
TI  - Cancer risk in a cohort of polio patients.
AB  - Poliomyelitis has hypothetically been associated with an increased risk of
      central nervous system (CNS) tumors. The present study was performed to examine
      not only the risk of CNS tumors but also the overall risk of cancer among a
      cohort of 5,883 polio patients. Patients diagnosed with acute poliomyelitis in
      the Danish capital, Copenhagen, between 1919 and 1954 were identified and
      followed with respect to cancer. Information on vital status and cancer diagnoses
      was obtained through linkage with the Danish Civil Registration System and the
      Danish Cancer Registry, respectively. The ratio of observed number of cancers to
      the number expected from population-based incidence rates, i.e., the standardized
      incidence ratio (SIR), served as measure of the relative cancer risk. Overall,
      717 cases of cancer were observed among 5,883 polio patients during 249,084
      person-years of follow-up vs. an expected number of 645 (SIR = 1.11 [95%
      confidence interval 1.03 to 1.20])). The increased risk was restricted to female
      polio patients (SIR = 1.18 [1.07 to 1.30]), among whom the risk was particularly
      high for breast cancer (SIR = 1.35 [1.12 to 1.61]) and for skin cancer (SIR =
      1.66 [1.32 to 2.07]). The risk of breast cancer was highest among women with a
      history of paralytic polio (SIR = 1.62 [1.24 to 2.10]). The observed number of
      CNS tumors did not exceed the expected (SIR = 1.09 [0.72 to 1.60]). Women
      diagnosed with poliomyelitis, in particular paralytic polio, may be at increased
      risk of breast cancer. There was no association between malignancies of the CNS
      and poliomyelitis.

PMID- 11304700
TI  - Diagnostic value of radiological breast imaging in a non-screening population.
AB  - The aim of this study was to assess the diagnostic performance of breast imaging
      in the diagnosis of breast cancer in a non-screening population. In a consecutive
      set of patients referred for mammography in one year, the results of palpation
      and radiological breast imaging were scored on a 5-point grading scale and linked
      to pathology as gold standard after a follow up period of one year. The
      diagnostic performance was studied by logistic regression analysis and ROC
      curves. There were 1,944 breast examinations in 1,890 patients and 3,816 breasts.
      Pathology results reported 118 malignancies in 115 women. With a cut-off point
      between benign and uncertain benign a sensitivity of 89% and a specificity of 98%
      was found for radiological imaging. ROC-curves showed a significant increase in
      diagnostic performance when radiology was added to results of palpation and age
      (p = 0.007). Radiological imaging tests have a large diagnostic value in the
      detection of breast cancer in addition to palpation and age. A sensitivity close
      to 100% could be reached.

PMID- 11304699
TI  - Distal bowel selectivity in the chemoprevention of experimental colon
      carcinogenesis by the non-steroidal anti-inflammatory drug nabumetone.
AB  - Use of non-steroidal anti-inflammatory drugs (NSAIDs) for chemoprevention of
      colon cancer has been hindered by their potential gastro-intestinal toxicity.
      Nabumetone, which is approximately 10 to 36 times safer than conventional NSAIDs,
      was evaluated in 2 models of experimental colon carcinogenesis. In azoxymethane
      (AOM)-treated Fisher 344 rats, nabumetone caused dose-dependent inhibition of
      aberrant crypt foci (ACF), with 750 and 1,500 ppm resulting in 15% and 37%
      reductions, respectively (p < 0.05). Moreover, complex ACF were reduced by 48% in
      the latter group. MIN mice studies confirmed the chemopreventive efficacy of
      nabumetone, with 900 ppm suppressing approximately half of the intestinal tumors.
      Interestingly, inhibition of intermediate biomarkers in both models was markedly
      greater in the distal than the proximal bowel. To mechanistically evaluate this
      regional selectivity, we assessed cyclo-oxygenase-2 (COX-2) expression in the
      uninvolved mucosa and demonstrated a 3- to 4-fold excess in the distal relative
      to the proximal bowel in both MIN mice and AOM-treated rats. We then investigated
      another putative NSAID target, peroxisome proliferator-activated receptor-delta
      (PPAR-delta) and demonstrated up-regulation during AOM-induced colonic
      tumorigenesis. Furthermore, in pre-neoplastic mucosa, there was a 3-fold excess
      of PPAR-delta in the distal colon. We demonstrate that nabumetone is an effective
      protective agent in both experimental models of colon carcinogenesis. The
      striking distal predilection of nabumetone may be, at least partially, explained
      by distal bowel over-expression of COX-2 and PPAR-delta.

PMID- 11304701
TI  - Introduction: perspectives on therapy with gay, lesbian, and bisexual clients.
AB  - The approach that mental health professionals have taken in working with gay,
      lesbian, and bisexual (GLB) clients has changed dramatically over the past 25
      years. Once viewed as being pathological in nature-either a sociopathic
      personality disorder or a sexual deviation-homosexuality is no long
      conceptualized as a "disorder" and instead is viewed within the broader context
      of human diversity. Even with such changes, many mental health professionals
      nonetheless retain subtle biases against working with gay, lesbian, and bisexual
      clients, and often lack the necessary information for working with them
      effectively. This issue of In Session provides a series of articles designed to
      help practicing therapists to become better aware of those clinical issues if
      they are to work with GLB individuals-which they are likely to do.

PMID- 11304702
TI  - Presenting problems among treatment-seeking gay, lesbian, and bisexual youth.
AB  - Gay, lesbian, and bisexual youth are at risk for a variety of clinical problems
      amenable to psychotherapeutic intervention. However, many psychotherapists may be
      unaware of the difficulties faced by this population. The purpose of this article
      is to familiarize therapists with presenting complaints common to psychotherapy
      seeking gay, lesbian, and bisexual youth. Some of these problems include
      homophobia among family, peers, and authority figures (often expressed at school
      or at work), depression, suicidality, social anxiety, and body image disturbance.
      We illustrate these important issues via four case examples.

PMID- 11304703
TI  - Cognitive-behavioral therapy with gay, lesbian, and bisexual clients.
AB  - Cognitive-behavioral therapy (CBT) can be adapted to a wide range of clinical
      difficulties and presenting problems that face lesbians, gay men, and bisexual
      persons. The following article presents general guidelines for and two case
      examples of the use of CBT. The first case is a gay male struggling with social
      phobia. This case is an example of how to adapt a structured, empirically
      supported cognitive-behavioral treatment focusing on social phobia to situations
      that are associated with his sexual orientation. The second is a woman struggling
      with multiple issues including coming out. This case provides an example of how
      to add specific cognitive-behavioral techniques to coming-out issues within the
      context of a more eclectic, longer-term therapy.

PMID- 11304704
TI  - Counteracting the effects of invisibility in work with lesbian patients.
AB  - Lesbian women frequently experience "invisibility," the failure of others to
      recognize the significance of their sexuality and partnership relations. Such
      invisibility can have deleterious effects, such as a reduced ability to relate
      life stories to others and thereby to extend and integrate aspects of identity
      and its healthy complexity. Although this invisibility often is intertwined with
      coming-out phenomena, it continues to exist in many social contexts throughout
      life. Therefore, it is important for psychotherapists to recognize and understand
      the concept of invisibility so that they do not perpetuate it within the therapy.
      Several case vignettes are used as examples of how invisibility can affect a
      woman's life and functioning and can be counteracted in therapy.

PMID- 11304705
TI  - Assessing basic HIV transmission risks and the contextual factors associated with
      HIV risk behavior in men who have sex with men.
AB  - HIV/AIDS remains a substantial health threat to men who have sex with men.
      Although new HIV medications have provided great benefits for many HIV-positive
      individuals, they have done little to protect HIV-negative men. Consequently,
      changing one's sexual practices remains the most effective way to reduce risk for
      HIV. However, to develop an effective intervention for reducing HIV risk, it is
      important to fully understand risk behavior. In this article, we detail the
      essential elements for conducting an HIV risk assessment as well as those
      contextual factors that may support risk behaviors. Further, we discuss the
      importance of procuring an HIV test and the critical issues that may arise
      because of testing for HIV as well as the critical issues that may result from
      testing HIV-positive. Finally, we illustrate how we integrate an HIV health risk
      assessment into a clinical interview.

PMID- 11304706
TI  - Treating the bisexual client.
AB  - Therapists, having recently come to terms with treating gay and lesbian clients,
      now must consider the issues that bisexual clients face. This article reviews the
      literature on what it means to identify as bisexual in a world where sexual
      identity is viewed as dichotomous, heterosexual at one end and gay or lesbian at
      the other end. The article explores sexual identity and its biological versus
      social origins, internalized biphobia, coming out, relationship patterns, and
      therapist issues. Two cases illustrate issues that might arise when a therapist
      is treating a bisexual client. The first case is a 17-year-old young woman who is
      accepting of her bisexual identity, and the second case is a 56-year-old woman,
      heterosexually identified and married, who suddenly fell in love with a woman.
      Concluding remarks focus on some future directions for research and work with
      bisexual clients.

PMID- 11304707
TI  - The importance of parental support in the lives of gay, lesbian, and bisexual
      individuals.
AB  - This article underscores the very important role that parental acceptance and
      support plays in furthering the psychological well-being of gay, lesbian, and
      bisexual individuals. Parents, Families, and Friends of Lesbians and Gays
      (PFLAG), an organization dedicated to this goal, has as its mission the support
      for family members, education of the public, and advocacy for equal rights for
      lesbians, gay men, and bisexuals. By "coming out" themselves, straight parents
      and relatives-including those in the mental health field-not only can extend the
      support they offer to their gay/lesbian/bisexual children and relatives but also
      play a significant role in reducing the stigma of being gay, lesbian, or bisexual
      and in mainstreaming gay, lesbian, and bisexual issues.

PMID- 11304708
TI  - Conceptual and ethical issues in therapy for the psychological problems of gay
      men, lesbians, and bisexuals.
AB  - Reviewed here are a number of conceptual and ethical issues surrounding the study
      and treatment of gay men, lesbians, and bisexuals (GLB), with particular emphasis
      on the frequently overlooked political and ethical dimensions of what therapists
      choose to treat, indeed, on the goals patients themselves want to work towards.
      Several issues are discussed, including the relevance and irrelevance of sexual
      orientation and the role of therapist biases in assessment and treatment
      planning, the need for better understanding of how the problems of GLB patients
      are construed and the associated dangers of stereotyping, the challenges of
      coming out and the ways therapists can help patients make the decision and how to
      implement it, the extra effort required to be a GLB person in terms of the
      formation of an unconventional social and sexual identity, the trust issues that
      can arise when one partner in a committed relationship requests protected sex,
      the challenges and rewards of parents "coming out" as family members of a gay son
      or daughter, the social invisibility of lesbians and the deleterious effects this
      can have on them, social support issues for GLB youth, and the need for
      professionals to take a broad, institutional community psychology perspective to
      their study and treatment of GLB individuals.

PMID- 11304709
TI  - Factors shaping the corpus callosum.

PMID- 11304710
TI  - Callosal connections correlate preferentially with ipsilateral cortical domains
      in cat areas 17 and 18, and with contralateral domains in the 17/18 transition
      zone.
AB  - Previous studies have shown that the distribution of callosal connections in the
      17/18 callosal zone of the cat is patchy at a small scale, but the mechanisms
      that determine this periodic pattern remain unclear. The present study
      investigated this issue by correlating the distribution of retrogradely labeled
      callosal cells with the underlying patterns of ocular dominance columns (ODCs)
      revealed transneuronally after intraocular injections of wheat germ agglutinin
      horseradish peroxidase. The density of labeled callosal cells was found to vary
      significantly between adjacent territories dominated by different eyes,
      indicating that the distribution of callosal cells is significantly biased toward
      domains that are eye specific. Moreover, callosal connections relate to the
      pattern of ODCs in a rather unique way: callosal cells correlate preferentially
      with contralateral ODCs within the 17/18 transition zone (TZ), and with
      ipsilateral ODCs in regions of areas 17 and 18 located outside the TZ. Similar
      results were obtained in cats raised with strabismus, indicating that the overlap
      between right and left ODCs present in normal cats does not influence the
      correlation between callosal neurons and ODCs. The results are consistent with
      the hypothesis that callosal linkages are stabilized during development by
      interhemispheric correlated activity driven by bilateral projections from
      temporal retina. It is proposed that developmental constraints imposed by both
      this retinally driven mechanism and the pattern of ODCs are likely to determine
      not only the association of callosal clusters with specific sets of ODCs, but
      also important aspects of the functional characteristics of the callosal pathway
      in cat striate cortex.

PMID- 11304711
TI  - Differential expression of GABA(B)R1 and GABA(B)R2 receptor immunoreactivity in
      neurochemically identified neurons of the rat neostriatum.
AB  - Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
      neostriatum. Functions of GABA are known to mediate GABA(A) and GABA(B)
      receptors. A functional GABA(B) receptor is known to compose of heteromeric
      subunits, namely the GABA(B)R1 and GABA(B)R2 subunits. Our previous report (Yung
      et al. [1999] Brain Res. 830:345-352) has demonstrated that all major
      subpopulations of striatal neurons express GABA(B)R1 immunoreactivity. The
      cellular localization of the second subunit of GABA(B) receptor protein, i.e.,
      GABA(B)R2 immunoreactivity, in the rat neostriatum is not yet known. By using a
      new commercially available specific antibody against GABA(B)R2,
      immunofluorescence was performed to investigate the cellular expression of
      GABA(B)R2 in neurochemically identified subpopulations of neurons in the rat
      neostriatum. Immunoreactivity for GABA(B)R2 was primarily found in the neuropil
      of the rat neostriatum. Double labeling revealed that those perikarya that
      expressed immunoreactivity for parvalbumin, choline acetyltransferase, nitric
      oxide synthase, glutamate receptor two, N-methyl-D-aspartate receptor one, or
      GABA(A)alpha1 receptor, respectively, did not express GABA(B)R2 immunoreactivity.
      In addition, perikarya and most of the neuropilar elements in the neostriatum
      that expressed glutamic acid decarboxylase 67 immunoreactivity were found to be
      GABA(B)R2-negative. In contrast, immunoreactivity for GABA(B)R1 was found to be
      expressed by all of the above neuronal subpopulations. Moreover, a vast number of
      SV2-immunoreactive profiles and a number of tyrosine hydroxylase-immunoreactive
      profiles in the neuropil of the neostriatum were found to display GABA(B)R2
      immunoreactivity. The present results indicate that there is a differential
      expression of GABA(B)R2 and GABA(B)R1 immunoreactivity in different
      subpopulations of striatal neurons that are identified by their specific
      neurochemical markers. Immunoreactivity for GABA(B)R2 is likely to localize in
      neuropilar elements of the neostriatum that may belong to non-GABAergic elements.
      These findings provide anatomical evidence of GABA(B)R2 receptor localization in
      the neostriatum that may have an important functional implication of the GABA(B)
      mediated functions in neurons of the neostriatum.

PMID- 11304712
TI  - Functional and anatomical localization of mu opioid receptors in the striatum,
      amygdala, and extended amygdala of the nonhuman primate.
AB  - The subregional distribution of mu opioid receptors and corresponding G-protein
      activation were examined in the striatum, amygdala, and extended amygdala of
      cynomolgus monkeys. The topography of mu binding sites was defined using
      autoradiography with [(3)H]DAMGO, a selective mu ligand. In adjacent sections,
      the distribution of receptor-activated G proteins was identified with DAMGO
      stimulated guanylyl 5'(gamma-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding.
      Within the striatum, the distribution of [(3)H]DAMGO binding sites was
      characterized by a distinct dorsal-ventral gradient with a higher concentration
      of binding sites at more rostral levels of the striatum. [(3)H]DAMGO binding was
      further distinguished by the presence of patch-like aggregations within the
      caudate, as well as smaller areas of very dense receptor binding sites,
      previously identified in human striatum as neurochemically unique domains of the
      accumbens and putamen (NUDAPs). The amygdala contained the highest concentration
      of [(3)H]DAMGO binding sites measured in this study, with the densest levels of
      binding noted within the basal, accessory basal, paralaminar, and medial nuclei.
      In the striatum and amygdala, the distribution of DAMGO-stimulated G-protein
      activation largely corresponded with the distribution of mu binding sites. The
      central and medial nuclei of the amygdala, however, were notable exceptions.
      Whereas the concentration of [(3)H]DAMGO binding sites in the central nucleus of
      the amygdala was very low, the concentration of DAMGO-stimulated G-protein
      activation in this nucleus, as measured with [(35)S]GTPgammaS binding, was
      relatively high compared to other portions of the amygdala containing much higher
      concentrations of [(3)H]DAMGO binding sites. The converse was true in the medial
      nucleus, where high concentrations of binding sites were associated with lower
      levels of DAMGO-stimulated G-protein activation. Finally, [(3)H]DAMGO and
      [(35)S]GTPgammaS binding within the amygdala, particularly the medial nucleus,
      formed a continuum with the substantia innominata and bed nucleus of the stria
      terminalis, supporting the concept of the extended amygdala in primates.

PMID- 11304713
TI  - Eye stalks or no eye stalks: a structural comparison of pupal development in the
      stalk-eyed fly Cyrtodiopsis and in Drosophila.
AB  - After emergence from the puparium, stalk-eyed flies of the family Diopsidae
      rapidly expand their head capsule so that the eyes and optic lobes are displaced
      at the ends of stalks that extend from the central head. Because the expansion
      takes place in only 15 minutes, we are especially interested in ontogenetic
      modifications that may facilitate such a rapid and dramatic change. To examine
      the pupal development of the brain, we used Bodian staining in the stalk-eyed
      fly, Cyrtodiopsis whitei and compared it with development in the fruit fly,
      Drosophila melanogaster, which serves as a "typical" dipteran example without eye
      stalks. Early in pupal development, the neuropil organization of the two species
      is fairly similar. In both species, columns are present in the outer medulla and
      giant fibers are discernible in the lobula plate. In contrast to D. melanogaster,
      C. whitei shows a small, neck-like constriction between the optic lobes and the
      rest of the brain. By 20% of pupal development, the divergence is more apparent,
      and by 30%, the future eye stalk and optic nerve of C. whitei has started to
      form. During the remaining 70% of development, the initially thick optic nerve
      narrows, and becomes gradually elongated, eventually coiling and folding
      throughout the short eye stalk. Similarly, the cuticle of the surrounding region
      becomes constricted, slightly elongated, and gradually appears more and more
      densely corrugated, like an accordion bellows. However, except for the formation
      of the optic nerve, the dense aggregation of cuticle around it, and a shift in
      orientation of the neuropils, the developmental programs of the two species are
      remarkably similar. This suggests that only a few aspects of development have
      been modified during the course of evolution to generate the stalk-eyed
      phenotype. At eclosion, the imago of C. whitei goes through a pumping process to
      inflate the eye stalks to their full length. Measurements of the diameter of the
      optic nerve before and after the expansion reveal only a small decrease. We
      propose that the cuticular folding of the eye stalk as well as the coiling of the
      optic nerve prepare the pupa well for the rapid and dramatic eye-stalk inflation
      after eclosion.

PMID- 11304714
TI  - Expression and estrogen regulation of brain-derived neurotrophic factor gene and
      protein in the forebrain of female prairie voles.
AB  - Brain-derived neurotrophic factor (BDNF) has been linked to the development,
      differentiation, and plasticity of the central nervous system. In the present
      study, we first used a highly specific affinity-purified antibody and a cRNA
      probe to generate a detailed mapping of BDNF immunoreactive (BDNF-ir) staining
      and mRNA labeling throughout the forebrain of female prairie voles. Our data
      revealed that (1) BDNF-ir cells were present essentially in the brain regions in
      which BDNF mRNA-labeled cells were found; (2) BDNF-ir fibers were distributed
      extensively throughout many forebrain regions; and (3) BDNF mRNA was also
      detected in some thalamic regions in which BDNF-ir fibers, but not immunostained
      cells, were present. With few exceptions, the distribution pattern of BDNF in the
      vole brain generally resembled the pattern found in rats. In a second experiment,
      we examined the effects of estrogen on BDNF expression. Ovariectomized prairie
      voles that were treated with estradiol benzoate had a higher level of BDNF mRNA
      labeling in the dentate gyrus and CA3 region of the hippocampus, as well as in
      the basolateral nucleus of the amygdala, than did ovariectomized voles that were
      treated with vehicle. In addition, estrogen treatment increased the density of
      BDNF-ir fibers in the lateral septum, dorsolateral area of the bed nucleus of the
      stria terminalis, and lateral habenular nucleus. These data suggest that estrogen
      may regulate BDNF at the level of gene and protein expression, and thus, BDNF may
      be in a position to mediate the effects of estrogen on the brain of the prairie
      vole.

PMID- 11304715
TI  - Transient expression of synaptic zinc during development of uncrossed
      retinogeniculate projections.
AB  - The transition metal zinc is an essential dietary constituent that is believed to
      serve an important intercellular signaling role at certain excitatory synapses in
      the central nervous system. In the present study, we used histochemical
      techniques to investigate the distribution of synaptic zinc during postnatal
      development of retinogeniculate projections in rats. From postnatal day (P) 1
      until P-21, the pattern of zinc histochemical staining in the dorsal lateral
      geniculate nucleus (LGNd) precisely matched the distribution of axon terminals
      from the ipsilateral eye that were labeled by anterograde transport of
      horseradish peroxidase. Regions of the LGNd that contained only crossed axons
      were devoid of zinc staining. Abnormalities in the distribution of uncrossed
      retinogeniculate projections in albino versus pigmented rats were paralleled by
      identical variations in localization of synaptic zinc. Unilateral enucleation on
      P-10 was followed within 5 days by loss of zinc staining in the LGNd ipsilateral
      to the removed eye without affecting staining in the contralateral nucleus.
      Finally, the ability to detect zinc histochemically in the LGNd ceased at
      approximately P-24. These findings provide evidence that zinc is sequestered
      within synaptic boutons of a subpopulation of retinal ganglion cells whose axons
      terminate on the ipsilateral side of the brain. The duration of zinc staining
      overlaps with the major period of axonal remodeling in the LGNd, suggesting that
      synaptically released zinc may play a role in postnatal refinement of
      retinogeniculate projections.

PMID- 11304716
TI  - Distribution of the major gamma-aminobutyric acid(A) receptor subunits in the
      basal ganglia and associated limbic brain areas of the adult rat.
AB  - Within the basal ganglia, gamma-aminobutyric acid (GABA) exerts a fundamental
      role as neurotransmitter of local circuit and projection neurons. Its fast
      hyperpolarizing action is mediated through GABA(A) receptors. These ligand-gated
      chloride channels are assembled from five subunits, which derive from multiple
      genes. Using immunocytochemistry, we investigated the distribution of 12 major
      GABA(A) receptor subunits (alpha1-5, beta1-3, gamma1-3, and delta) in the basal
      ganglia and associated limbic brain areas of the rat. Immunoreactivity for an
      additional subunit (subunit alpha6) was not observed. The striatum, the nucleus
      accumbens, and the olfactory tubercle displayed strong, diffuse staining for the
      subunits alpha2, alpha4, beta3, and delta presumably located on dendrites of the
      principal medium spiny neurons. Subunit alpha1-, beta2-, and gamma2
      immunoreactivities were apparently mostly restricted to interneurons of these
      areas. In contrast, the globus pallidus, the entopeduncular nucleus, the ventral
      pallidum, the subthalamic nucleus, and the substantia nigra pars reticulata
      revealed dense networks of presumable dendrites of resident projection neurons,
      which were darkly labeled for subunit alpha1-, beta2-, and gamma2
      immunoreactivities. The globus pallidus, ventral pallidum, entopeduncular
      nucleus, and substantia nigra pars reticulata, all areas receiving innervations
      from the striatum, displayed strong subunit gamma1-immunoreactivity compared to
      other brain areas. In the substantia nigra pars compacta and in the ventral
      tegmental area, numerous presumptive dopaminergic neurons were labeled for
      subunits alpha3, gamma3, and/or delta. This highly heterogeneous distribution of
      individual GABA(A) receptor subunits suggests the existence of differently
      assembled, and presumably also functionally different, GABA(A) receptors within
      individual nuclei of the basal ganglia and associated limbic brain areas.

PMID- 11304717
TI  - Target-derived BDNF (brain-derived neurotrophic factor) is essential for the
      survival of developing neurons in the isthmo-optic nucleus.
AB  - Neurons in the peripheral nervous system depend on single neurotrophic factors,
      whereas those in the brain are thought to utilize many different trophic factors.
      This study examined whether some neurons in the brain critically depend on a
      single trophic factor during development. Neurons in the isthmo-optic nucleus
      (ION) of chick embryos respond to exogenous brain-derived neurotrophic factor
      (BDNF). Relatively high concentrations of endogenous BDNF were present in the ION
      of 14-18-day-old chick embryos. ION target cells in the retina were immunolabeled
      for BDNF but showed surprisingly low levels of BDNF mRNA. These data suggest that
      ION target cells derive some BDNF from other retinal sources. No BDNF mRNA was
      detected in the ION itself. ION neurons had a very efficient retrograde transport
      system for BDNF and exogenous BDNF arrived in the ION intact. When the ION was
      deprived of endogenous trkB ligands by injection of trkB fusion proteins in the
      eye, cell death of ION neurons was enhanced, and this effect was mimicked by BDNF
      specific blocking antibodies in the eye. TrkB fusion proteins in the retina
      induced cell death of ION neurons prior to visible effects on ION target cells in
      the retina. Immunolabel for endogenous BDNF was sparse in pyknotic ION neurons,
      suggesting that ION neurons with low BDNF content were eliminated by apoptosis.
      These data show that BDNF is an essential target-derived trophic factor for
      developing ION neurons and thereby validate the neurotrophic hypothesis for at
      least one neuronal population in the brain.

PMID- 11304718
TI  - Bioequivalence evaluation of two brands of cefuroxime 500 mg tablets (Cefuzime
      and Zinnat) in healthy human volunteers.
AB  - A bioequivalence study of two oral formulations of 500 mg cefuroxime axetil was
      carried out in 24 healthy volunteers following a single dose, standard two
      treatment cross-over design at the College of Pharmacy, King Saud University,
      Riyadh, Saudi Arabia, working jointly with King Khalid University Hospital. The
      two formulations used were Cefuzime (Julphar, United Arab Emirates) as the test
      and Zinnat (Glaxo Wellcome, England) as the reference product. Both test and
      reference tablets were administered to each subject after an overnight fasting on
      two treatment days separated by a 1-week washout period. After dosing, serial
      blood samples were collected for a period of 8 h. Plasma harvested from blood was
      analysed for cefuroxime by a sensitive, reproducible and accurate high pressure
      liquid chromatography (HPLC) method. Various pharmacokinetic parameters including
      AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2) and K(el) were determined from
      plasma concentrations of both formulations and found to be in good agreement with
      reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for
      bioequivalence after log-transformation of data. No significant difference was
      found based on an analysis of variance (ANOVA); 90% confidence interval for
      test/reference ratio of these parameters were found within bioequivalence
      acceptance range of 80-125%. Based on these statistical inferences, it was
      concluded that Cefuzime is bioequivalent to Zinnat.

PMID- 11304719
TI  - Comparative pharmacokinetics, safety, and tolerability after subcutaneous
      administration of recombinant human erythropoietin formulated with different
      stabilizers.
AB  - This report summarizes the results of two double-blind, single-center, randomized
      studies that used a two-period crossover design. The objective of these two
      studies was to compare the safety, tolerability, pharmacokinetics, and pain score
      at the subcutaneous (sc) injection site of a phosphate-buffered recombinant human
      erythropoietin (EPREX, epoetin alfa, r-HuEPO) formulated with a new stabilizer
      (glycine and Polysorbate 80) with the commercially available EPREX formulations,
      which uses human serum albumin (HSA) as the stabilizer. Twenty-four healthy male
      volunteers were enrolled in each of the two studies. In the first study, subjects
      received a single 150 IU/kg sc dose of r-HuEPO using the 2000 IU/mL (2K)
      phosphate-buffered formulation with or without the new stabilizer (12
      subjects/group). In the second study, subjects received a single 750 IU/kg sc
      dose of r-HuEPO using the 40 000 IU/mL (40K) phosphate-buffered formulation with
      or without the new stabilizer (12 subjects/group). In each study, r-HuEPO was
      administered over two separate dosing periods, each separated with a 28-day
      washout period. There were no significant differences in AUC and C(max) for
      either strength of r-HuEPO formulated with or without the new stabilizer,
      indicating that the absorption and disposition characteristics of the two
      formulations were similar after sc administration. Both r-HuEPO strengths with
      and without the new stabilizer were safe and well tolerated; the safety and
      tolerability profiles of both formulations for each r-HuEPO concentration were
      comparable. There were no statistically significant differences in pain score for
      either strength of r-HuEPO with and without the new stabilizer. It was concluded
      that the two phosphate-buffered r-HuEPO concentrations formulated with and
      without the new stabilizer are pharmacokinetically equivalent.

PMID- 11304720
TI  - Pharmacokinetics and protein binding of the selective neuronal nitric oxide
      synthase inhibitor 7-nitroindazole.
AB  - Utilization of nitric oxide (NO) synthase (NOS) inhibitors to probe the role of
      NO in various central nervous system processes requires use of an inhibitor
      selective for neuronal NOS, and is facilitated by knowledge of the
      pharmacokinetics of the inhibitor. The present project was undertaken to
      elucidate the disposition of the selective neuronal NOS inhibitor 7-nitroindazole
      (7-NI). A simple, specific HPLC assay was developed with requisite sensitivity to
      quantitate 7-NI in serum after administration of pharmacologically relevant
      doses. Further experiments were performed to assess the effects of administered
      dose on 7-NI disposition. 7-NI displayed marked nonlinearity, consistent with
      saturable elimination, when administered by ip injection in peanut oil. The
      nonlinearity was related to total dose, but not to the concentration of 7-NI in
      the vehicle. Binding of 7-NI in rat serum was concentration-independent and does
      not contribute to the nonlinearity. Various formulations for iv administration of
      this water-insoluble compound were evaluated; the optimal vehicle, from the
      standpoint of 7-NI solubility, appeared to inhibit the clearance of 7-NI from the
      systemic circulation. Considering the nonlinear disposition of 7-NI, knowledge of
      the pharmacokinetics of this inhibitor is requisite to designing administration
      protocols to achieve the desired magnitude and duration of NOS inhibition.

PMID- 11304721
TI  - Absence of pharmacokinetic interaction between orally co-administered naproxen
      sodium and diphenhydramine hydrochloride.
AB  - The potential for a pharmacokinetic interaction between naproxen and
      diphenhydramine was examined in a randomized three-way crossover design with a 1
      week washout between dosing. Single oral doses of 220 mg of naproxen sodium and
      50 mg of diphenhydramine hydrochloride were given separately and together to 30
      healthy male and female subjects. Heparinized blood samples obtained for 48 h
      postdose were assayed for plasma naproxen and diphenhydramine concentrations
      using validated high-performance liquid chromatography (HPLC) and gas
      chromatography (GC) assay methods, respectively. The area under the plasma
      concentration-time curve (AUC), maximum plasma concentrations (C(max)), time of
      C(max) (T(max)) and terminal exponential half-life (t(1/2,z)), were analysed for
      significant treatment differences by analysis of variance (ANOVA). Based on
      absence of significant treatment effects on AUC and C(max), single-dose oral co
      administration of 220 mg of naproxen sodium with 50 mg of diphenhydramine
      hydrochloride does not alter the pharmacokinetics of either naproxen or
      diphenhydramine. Significant treatment differences seen for naproxen T(max) (0.3
      h, males only) and diphenhydramine t(1/2,z) (0.8 h, females only) were minor and
      are unlikely to have therapeutic consequences. Thus, efficacy and safety of
      concomitant naproxen and diphenhydramine should not be altered due to a
      pharmacokinetic interaction.

PMID- 11304722
TI  - Effect of naproxen co-administration on valproate disposition.
AB  - The effects of co-administration of the antiepileptic agent valproic acid (VPA)
      and the non-steroidal anti-inflammatory drug naproxen (NAP) on their relative
      dispositions (particularly with respect to glucuronidation) were investigated in
      human volunteers. Seven healthy males received each drug alone and then in
      combination (orally twice daily for seven days, 500 mg sodium VPA, 500 mg NAP).
      On day 7 of each dosing phase, serial plasma and 24 h urine samples were
      collected for analysis. Co-administration of NAP resulted in significant
      increases (about 20%, p<0.05) in the apparent plasma clearance of total VPA and
      in the unbound fraction of VPA in plasma, with the apparent plasma clearance of
      unbound VPA being unchanged. There were associated increases in the formation
      clearances to urinary VPA-glucuronide and 3-oxo-VPA, though these were relatively
      greater for the glucuronidation pathway (and remained significant when formation
      clearances were calculated using the unbound fraction of drug in plasma). The
      data thus point to a shift towards glucuronidation as a result of the NAP-induced
      increase in the unbound fraction of VPA in plasma. By contrast, VPA co
      administration caused a decrease (of about 10%, p<0.05) in the apparent plasma
      clearance of total NAP. Taken in hand with in vitro results showing a VPA-induced
      displacement (of about 40%) of NAP from plasma protein binding sites, the data
      strongly support a role for diminished glucuronidation of NAP and its desmethyl
      metabolite in the presence of co-administered VPA.

PMID- 11304723
TI  - Comparative bioavailability of two cefadroxil formulations in healthy human
      volunteers after a single-dose administration.
AB  - OBJECTIVE: To compare the bioavailability of two cefadroxil capsule (500 mg)
      formulations (Cefadroxila from Eurofarma Laboratorios Ltd, Brazil, as test
      formulation and Cefamox from Bristol-Myers Squibb, Brazil S.A. as reference
      formulation) in 24 volunteers of both sexes. MATERIAL AND METHODS: The study was
      conducted open with randomized two-period crossover design and a 1-week washout
      period. Plasma samples were obtained over a 12-h interval. Cefadroxil
      concentrations were analysed by combined reversed-phase liquid chromatography and
      tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization
      using a selected ion monitoring method. From the cefadroxil plasma concentration
      versus time curves the following pharmacokinetic parameters were obtained:
      AUC(last), AUC(0-infinity) and C(max). RESULTS: Geometric mean of
      Cefadroxila/Cefamox 500 mg individual percent ratio was 103.97% for AUC(last),
      104.08% for AUC(0-infinity) and 95.23% for C(max). The 90% confidence intervals
      (CI) were 98.14-110.16%, 98.37-110.12%, and 85.59-105.96%, respectively.
      CONCLUSION: Since the 90% CI for C(max), AUC(last) and AUC(0-infinity) were
      within the 80-125% interval proposed by the Food and Drug Administration, it was
      concluded that the Cefadroxila 500 mg capsule was bioequivalent to the Cefamox
      500 mg capsule, according to both the rate and extent of absorption.

PMID- 11304724
TI  - Human cell lines as an in vitro/in vivo model for prostate carcinogenesis and
      progression.
AB  - BACKGROUND: The study of prostate carcinogenesis and tumor progression is made
      difficult by the lack of appropriate in vitro and in vivo models. High prevalence
      of prostatic intra-epithelial neoplasia and latent prostatic carcinoma,
      representing multiple steps in carcinogenesis to invasive carcinoma, are relevant
      targets for cancer prevention. From the RWPE-1, immortalized, non-tumorigenic,
      human prostate epithelial cell line, we have derived four tumorigenic cell lines
      with progressive malignant characteristics. METHODS: Cell lines were derived by
      exposure of RWPE-1 to N-methyl-N-nitrosourea (MNU), selected and cloned in vivo
      and in vitro, and characterized by prostatic epithelial and differentiation
      markers, karyotype analysis, anchorage-independent growth, invasiveness,
      tumorigenicity, and pathology of the derived tumors. RESULTS: Cytokeratins 8 and
      18, androgen receptor, and prostate-specific antigen expression in response to
      androgen, confirm prostatic epithelial origin. RWPE-1 cells do not grow in agar
      and are not tumorigenic in mice, but the growth, tumorigenicity, and tumor
      pathology of the MNU cell lines correlate with their invasive ability. The WPE1
      NA22 (least malignant) form small, well-differentiated, and WPE1-NB26 cells (most
      malignant) form large, poorly differentiated, invasive tumors. Overall, loss of
      heterozygosity for chromosomes 7q, 13q, 18q, and 22, and gain of 5, 9q, 11q, and
      20, was observed. The MNU cell lines, in order of increasing malignancy are; WPE1
      NA22, WPE1-NB14, WPE1-NB11, and WPE1-NB26. CONCLUSIONS: This family of cell lines
      with a common lineage represents a unique and relevant model which mimics stages
      in prostatic intra-epithelial neoplasia (PIN) and progression to invasive cancer,
      and can be used to study carcinogenesis, progression, intervention, and
      chemoprevention.

PMID- 11304725
TI  - Similar rates of exponential decrease in serum concentrations of free prostate
      specific antigen (PSA), PSA complexed to alpha-1-antichymotrypsin, and human
      glandular kallikrein 2 (hK2) in prostate cancer patients treated with GnRH
      analogues.
AB  - BACKGROUND: Our recently reported finding of rapid bi-exponential elimination of
      free prostate-specific antigen (PSA) after radical retropubic prostatectomy in
      patients with moderately elevated PSA levels, which contrasted a very slow,
      linear elimination of PSA complexed to alpha-1-antichymotrypsin (ACT), prompted
      us to study whether these elimination rates were applicable for patients selected
      for castration treatment with very high pretreatment concentrations of PSA in
      serum. In addition, serum concentrations of hK2, the activator of proPSA, were
      measured. METHODS: Pretreatment serum was obtained from 21 previously untreated
      prostate cancer patients due for hormonal treatment with a GnRH-analog. Samples
      were also collected during treatment up to a minimum of 24 weeks at 2-week
      intervals and analyzed with immunofluorometric assays for free PSA (PSA-F), PSA
      complexed to alpha-1-antichymotrypsin (PSA-ACT), total PSA (PSA-T), and human
      kallikrein 2 (hK2). For pharmaco-kinetic analysis the serum concentrations of hK2
      and PSA forms for each patient were plotted against time both before and after
      logarithmic transformation and the half-lives were calculated as ln2/k. RESULTS:
      Median pretreatment serum concentrations were 322 ng/ml (range, 1.9-2210) for PSA
      T, 27.8 ng/ml (range, 1.14-259) for PSA-F, and 207 ng/ml (range, 0.8-2080) for
      PSA-ACT. All patients had castrate levels of serum testosterone (< 2.5 nmol/l) in
      less than 21 days after initiation of GnRH-analog treatment. It was possible to
      evaluate data from 19/21 patients which showed an exponential decrease of all PSA
      concentrations in serum, with mean half-lives of 12.9 days (range, 7.3-30) for
      PSA-T, 15.5 days (range, 7.7-37.5) for PSA-F, and 12.3 days (range, 6.6-30) for
      PSA-ACT. Median pretreatment percent free PSA (PSA-F/PSA-T) was 12% compared to
      18% at nadir. The median pretreatment level of hK2 was 3.5 ng/ml (range, 0.29
      30.3). There was an exponential decrease in hK2 concentrations in serum after
      initiation of hormonal treatment with a mean half-life of 18.7 days (range, 7.5
      37.5). CONCLUSIONS: For the majority of patients with hormonally treated prostate
      cancer the serum concentrations of PSA-T, PSA-F, PSA-ACT, and hK2 decreased
      slowly in parallel and mono-exponentially after initiation of treatment. Mean
      half-lives were between 12 and 19 days.

PMID- 11304726
TI  - Antitumor effect of an HER2-specific antibody-toxin fusion protein on human
      prostate cancer cells.
AB  - BACKGROUND: HER2/neu has been implicated in the oncogenesis of human prostate
      cancer. Clinical studies have suggested that overexpression of HER2 may be one of
      the indicators of poor prognosis in prostate cancer patients. METHODS: We used
      Western blot analysis to examine the expression of HER2 in a panel of established
      human prostate cancer cell lines and used an MTT assay to evaluate the
      cytotoxicity on these cells of a recombinant fusion protein consisting of an HER2
      specific single-chain antibody and the Pseudomonas exotoxin A, scFv(FRP5)-ETA.
      RESULTS: LNCaP cells express high levels of HER2 protein. Exposure of LNCaP cells
      to scFv(FRP5)-ETA caused remarkable cell death. In contrast, PC3M cells, which
      express an undetectable level of HER2 protein, were resistant to scFv(FRP5)-ETA
      induced cytotoxicity. MDA PCa 2a, MDA PCa 2b, and DU145 cells express low-to
      medium levels of HER2 protein and showed an HER2 level-dependent response to
      scFv(FRP5)-ETA-induced cytotoxicity. The scFv(FRP5)-ETA-induced cytotoxicity of
      LNCaP cells could be inhibited by an anti-HER2 monoclonal antibody (mAb), which
      downregulated the levels of HER2 protein, indicating the specificity of
      scFv(FRP5)-ETA in inducing cytotoxicity in LNCaP cells. Using an apoptosis ELISA,
      we demonstrated that scFv(FRP5)-ETA induced apoptosis in LNCaP cells. The
      apoptosis was inhibited by the presence of dihydrotestosterone (DHT) in culture
      medium. Exposure of LNCaP cells to scFv(FRP5)-ETA caused reduction in the level
      of the prostate-specific antigen (PSA). CONCLUSIONS: Our data suggest that
      scFv(FRP5)-ETA might be a useful agent for the treatment of human prostate cancer
      cells with high levels of HER2 expression.

PMID- 11304727
TI  - High-grade prostate intraepithelial neoplasia shares cytogenetic alterations with
      invasive prostate cancer.
AB  - BACKGROUND: High-grade prostate intraepithelial neoplasia (PIN) is the most
      likely precursor of prostate adenocarcinoma. However, the relationship between
      this lesion and prostate cancer has not yet been established. The detection of
      cytogenetic changes in the lesions prior to prostate adenocarcinoma would be
      useful in demonstrating such a pathogenic relationship. METHODS: Twenty eight
      high-grade PIN cases were found among 57 specimens of radical prostatectomy
      performed for clinically localized prostate cancer. Fluorescence in situ
      hybridization (FISH) analysis using centromeric probes to enumerate chromosomes
      7, 8, 10, and 12 was performed to study the numerical chromosome alterations.
      FISH analysis was carried out over isolated nuclei obtained from high-grade PIN
      areas and prostate cancer foci in the same prostatectomy specimen. RESULTS: Of
      the 28 suitable cases it was possible to complete the study in 26 tumor and 20
      PIN areas. The remaining cases were excluded because of insufficient tissue or
      poor preservation. Cytogenetic alterations (aneuploidy) were found in 16 of the
      26 (62%) tumors studied. The most frequent chromosome alteration was trisomy 7,
      detected in 12 (75%) aneuploid tumors, followed by monosomy 8 present in 5 (31%)
      aneuploid tumors. Trisomy 7 was also the most frequent isolated chromosome
      alteration since it was detected in 7 (44%) tumors. Thirteen of 20 (65%) PIN
      cases were aneuploid when studied by FISH. Trisomy 7, trisomy 8, and monosomy 8
      were the most common cytogenetic alterations in the 20 PIN areas studied, being
      observed in nine (45%), six (30%), and four (20%) cases, respectively. FISH
      analysis showed a high correlation (75% cases) in ploidy and pattern of
      cytogenetic alterations between high-grade PIN areas and the paired prostate
      cancer focus in the same specimen. CONCLUSIONS: The above results show a
      cytogenetic link between high-grade PIN and prostate cancer, suggesting that the
      former could be an early form of prostate cancer.

PMID- 11304728
TI  - Widely used prostate carcinoma cell lines share common origins.
AB  - BACKGROUND: Cross-contamination is a persistent problem in the establishment and
      maintenance of mammalian cell lines. The observation that the cell lines PC-3,
      ALVA-31, and PPC-1 all have a homozygous deletion of the alpha-catenin gene
      prompted us to investigate the uniqueness of these and several other widely used
      prostate carcinoma cell lines. METHODS: The genetic backgrounds of the putative
      human prostate cell lines (ALVA-31, ALVA-41, BPH-1, DU 145, JCA-1, LAPC-4, LNCaP,
      NCI-H660, ND-1, PC-3, PC-3MM2, PC-346C, PPC-1, and TSU-Pr1) were analyzed by
      cytogenetics, mutation analysis, and DNA profiling. RESULTS: Similarities between
      several groups of cell lines were found. ALVA-31, ALVA-41, PC-3, PC-3MM2, and PPC
      1 all have a deletion of a C in codon 138 of the p53 gene and show almost
      identical DNA profiles. The ND-1 cell line has two p53 mutations that are
      identical to the mutations found in DU 145. These two cell lines also share a
      high number of structural chromosomal abnormalities and nearly identical DNA
      profiles. The cell lines TSU-Pr1 and JCA-1 share an identical p53 mutation in
      exon 5 and identical DNA profiles. CONCLUSIONS: Several widely used prostate
      carcinoma cell lines apparently have identities in common. The knowledge that
      some of these cell lines are derivatives of one another prompts re-evaluation of
      previously obtained results.

PMID- 11304729
TI  - High-grade prostate cancer is associated with low serum testosterone levels.
AB  - BACKGROUND: The aim of this study was to assess whether low serum testosterone
      levels in men with newly diagnosed prostate cancer have an association to the
      endocrine status, prostate-specific antigen (PSA) levels, Gleason score, and
      androgen receptor expression. METHODS: Besides a full clinical work-up, the
      following hormones were quantified in men with newly diagnosed prostate cancer by
      serum analysis: total testosterone, human luteinising hormone (hLH), human
      follicle stimulating hormone (hFSH), estradiol, and dehydroepiandrostendione
      (DHEA). In a subgroup of men, androgen receptor expression was determined
      immunohistochemically. RESULTS: One hundred and fifty six patients (65.7 +/- 8.5
      yrs) with a mean PSA of 29.8 ng/ml (median: 7.4 ng/ml) were analysed. Fifty-two
      patients (33%) had a partial androgen deficiency (serum testosterone < 3.0
      ng/ml). These men had lower hLH (3.3 vs. 5.9 mIU/ml), hFSH (6.2 vs. 8.4 mIU/ml),
      and estradiol (18.8 vs. 29.1 pg/ml) serum levels. Mean Gleason score was higher
      (7.4 vs. 6.2) in men with a low serum testosterone, PSA-levels were lower (25.3
      vs. 31.9 ng/ml). Mean testosterone levels decreased from 4.1 +/- 1.7 ng/ml in
      patients with Gleason scores < or = 5 to 2.8 +/- 2.7 ng/ml with Gleason scores >
      or = 8. Androgen receptor expression was higher in patients with low serum
      testosterone. CONCLUSIONS: Patients with high Gleason score prostate cancer have
      lower testosterone and estradiol serum levels. The fact that gonadotropins were
      lower in parallel suggests a tumor-mediated suppression of the hypothalamic
      pituitary-gonadal hormone axis particularly in men with high Gleason score
      tumours.

PMID- 11304730
TI  - Myristoleic acid, a cytotoxic component in the extract from Serenoa repens,
      induces apoptosis and necrosis in human prostatic LNCaP cells.
AB  - BACKGROUND: Prostatic tumors are well known to progress to hormonal therapy
      resistant terminal states. At this stage, there are no chemotherapeutic agents to
      affect clinical outcome. An effective cell death inducer for these prostate cells
      may be a candidate as an attractive antitumor agent. The extracts from S. repens
      have been used to improve the state of prostatic diseases and we have attempted
      to identify the effective component from the extract. METHODS: Cell viability was
      examined in LNCaP cells, an in vitro model for hormonal therapy-resistant
      prostatic tumor. RESULTS: We found that exposure of the extract from S. repens
      resulted in cell death of LNCaP cells. We also identified myristoleic acid as one
      of the cytotoxic components in the extract. The cell death exhibited both
      apoptotic and necrotic nuclear morphology as determined by Hoechst 33342
      staining. Cell death was also partially associated with caspase activation.
      CONCLUSIONS: It was demonstrated that the extract from S. repens and myristoleic
      acid induces mixed cell death of apoptosis and necrosis in LNCaP cells. These
      results suggest that the extract and myristoleic acid may develop attractive new
      tools for the treatment of prostate cancer.

PMID- 11304731
TI  - Androgen receptor expression in androgen-independent prostate cancer cell lines.
AB  - BACKGROUND: Almost all attempts at establishing prostate carcinoma cell lines
      have resulted in generation of cells that are androgen-independent, including
      commonly used LNCaP which expresses androgen receptor (AR) and AR-negative Du145
      and PC-3. We attempted to clarify the mechanism(s) responsible for the failure to
      respond to androgen. METHODS: Cell lines LNCaP, CWR22R, PC-3, Du145, and CA7T2CL
      were used to examine the AR promoter function with a reporter gene assay and its
      methylation status by Southern blot, PCR of bisulfite-converted DNA, and 5-aza-2'
      deoxycytidine treatment. Structural abnormalities of the AR were identified by
      sequencing of reverse-transcribed mRNA. RESULTS: All tested AR-positive prostate
      carcinoma cells were capable of AR transcription at a significantly higher level
      than PC-3 and Du145, thus suggesting relative deficiency of the transcription
      factors in the AR-negative cells, further associated with methylation.
      Examination of CWR22R cells, which express the AR but are androgen-independent,
      identified an in-frame duplication of exon 3, which resulted in insertion of 39
      amino acids in the DNA-binding domain. CONCLUSIONS: Relative deficiency of
      transcription factors associated with methylation is responsible for the lack of
      AR promoter function in most of AR-negative cell lines. Mutations in the AR gene
      are present in the cells that express the AR but are androgen-independent.

PMID- 11304732
TI  - Estimation of gender bias in clinical trials.
AB  - The perception is that the clinical trials enterprise has been biased in favour
      of males by devoting a disproportionate effort to males and to the diseases and
      conditions afflicting them - a perception reinforced by a few high profile male
      only heart trials undertaken in the 1970s and 1980s. The perception was
      sufficient to cause the U.S.A. Congress to enact legislation to require that a
      clinical trial 'is designed and carried out in a manner sufficient to provide for
      a valid analysis of whether the variables being studied in the trial affect women
      ...differently than other subjects in the trial'. Observed effort differentials
      are based on counts of single-gender trials indexed in MEDLINE and published in
      U.S. journals. Differentials are compared to those expected using male-female
      differentials in mortality and years of potential life loss due to mortality
      before age 65 to estimate effort bias. The ratios of female-only to male-only
      published trials were 0.53, 0.89 and 0.95 for the decades of 1966-1975, 1976-1985
      and 1986-1995, respectively. The expected ratios, if single-gender trials were
      done in proportion to female-male mortality differentials, would be 0.57, 0.56
      and 0.57, respectively. The differences in observed versus expected female to
      male ratios correspond to a slight excess of male-only trials in the decade of
      1966-1975 and to sizeable excesses in female-only trials in the decades of 1976
      1985 and 1986-1995. The results do not support the perception that women have
      been understudied relative to males in clinical trials. Most differentials favour
      females, whether based on mortality or years of potential life loss due to
      mortality before age 65 years.

PMID- 11304733
TI  - Joint testing of mortality and a non-fatal outcome in clinical trials.
AB  - The following procedures are proposed for clinical trials of potentially lethal
      diseases with a non-fatal primary outcome: (i) comparison of treatments on worst
      rank scores combining mortality and the non-fatal outcome; (ii) testing first for
      mortality differences, and then for differences on the worst-rank scoring if
      there is no significant evidence for mortality differences. Power and control of
      type I error rate while testing mortality and worst-rank scores by Bonferroni or
      closed testing procedures are compared. Used together these procedures improve
      power to detect treatments with favourable effects on both mortality and the
      designated non-fatal outcome, while reducing the likelihood of declaring that a
      treatment benefits patients when undetected adverse effects on mortality are
      present.

PMID- 11304734
TI  - A methodology for analysing a repeated measures and survival outcome
      simultaneously.
AB  - A considerable body of literature has arisen over the past 15 years for analysing
      univariate repeated measures data. It is rare in applied biomedical research,
      however, for interest to be restricted to a single outcome measure. In previous
      work, Rochon considered the case of bivariate repeated measures data in which
      each outcome is a discrete or continuous random variable. A GEE model was
      prescribed to relate each set of repeated measures to important explanatory
      variables. The 'seemingly unrelated regression' model was then applied to combine
      the pair of GEE models into an overall analysis framework. In this paper, we
      extend this approach to the case in which one endpoint is a repeated measures
      outcome but the second is a survival endpoint. Estimation and hypothesis testing
      issues are addressed and the methodology is illustrated with an example.

PMID- 11304735
TI  - Power comparison of robust approximate and non-parametric tests for the analysis
      of cross-over trials.
AB  - The main advantage of cross-over designs in practice is the use of a smaller
      number of subjects to produce treatment comparisons with sufficient precision.
      Bellavance and Tardif proposed a non-parametric approach to test the hypotheses
      of direct treatment and carry-over effects for the three-treatment three-period
      and six sequences cross-over design and showed the high asymptotic efficiency of
      their approach relative to the classical F-test based on ordinary least squares
      (OLS). In a more recent paper, Ohrvik suggested another non-parametric method for
      the analysis of cross-over trials. The power of these two non-parametric
      approaches is evaluated for small sample sizes via simulations, and compared to
      the power of the usual analysis of variance model based on OLS and a modified F
      test approximation that take into account the correlation structure of the
      repeated measurements within subjects. Different covariance structures, sample
      sizes, and probability distributions for the responses, namely normal and gamma,
      are used in the simulations to evaluate the power and robustness of these
      different methods of analysis.

PMID- 11304736
TI  - Partial imputation approach to analysis of repeated measurements with dependent
      drop-outs.
AB  - In clinical trials repeated measurements of a response variable are usually taken
      at prespecified time-points to compare the treatment effects. However, the
      comparison of treatment effects is often complicated by missing data caused by
      the withdrawal of some patients before the end of the study (that is, drop-outs).
      When the drop-out process depends on the response variable of interest, ignoring
      missing data may lead to biased comparison of the treatment effect. In this
      paper, conditions for ignoring the dependent missingness are investigated and a
      new approach using the usual testing procedure based on data with partial
      carrying-forward imputation is proposed. The proposed approach is conceptually
      and practically simple, and is motivated by making incremental improvement on the
      familiar 'all available data' (AAD) approach and the 'last value carrying
      forward' (LVCF) approach, which are commonly used in data analysis with drop-outs
      by practitioners. It is also compared favourably to the mixed-effect model
      approach with dependent drop-outs. Simulations and real data are used to evaluate
      and illustrate statistical properties of the proposed approach. The principle of
      the proposed approach can also be extended to using other imputation methods such
      as the multiple imputation.

PMID- 11304737
TI  - Comparisons of two-part models with competitors.
AB  - Two-part models arise when there is a clump of 0 observations in a distribution
      of continuous non-negative responses. Several methods for comparing two such
      distributions are available. These include the straightforward application of the
      z-test (or t-test), the Wilcoxon-Mann-Whitney rank sum test, the Kolmogorov
      Smirnov test, and three tests that use a 2 degree of freedom chi(2) test based on
      the sum of the test for equality of proportions and a conditional chi(2) test for
      the continuous responses. This conditional test may be the z-test, the rank sum
      test, or the chi(2) corresponding to the Kolmogorov-Smirnov test. This study
      compares the size and power of several of these methods. All tests have the
      appropriate distribution under the null hypothesis if the distribution of the
      continuous part has finite moments. If it does not, the z-test has no power to
      detect any alternatives. It is found that the 2 d.f. tests are superior to the
      others when the larger proportion of 0 values corresponds to the population with
      the larger mean. If the reverse holds, the difference in the proportion of zeros
      reinforces the difference in means and some single-part models (the rank sum or
      Kolmogorov-Smirnov) do best. In those cases, the two-part models are not far
      behind, although statistically significantly poorer with respect to power.
      Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11304738
TI  - Power and sample size requirements for two-part models.
AB  - Two-part models assume the data has a probability mass at zero and a continuous
      response for values greater than 0. We construct tests based on the proportion of
      zeros and the difference among the positive values of a response giving rise to a
      two degree of freedom chi(2) test. This note gives the non-centrality parameter
      and finds the power for the test. The power is compared to the simulation results
      in a recent paper. We derive sample size calculations. We note that some
      modifications of this procedure may provide better tests if the non-zero
      responses are discrete. Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11304739
TI  - Two-phase shelf-life estimation.
AB  - Unlike most drug products, some drug products must be stored at several
      temperatures, such as -20 degrees C, 5 degrees C and 25 degrees C, in order to
      maintain the stability of the drug products. Drug products of this kind are
      usually referred to as frozen drug products. The determination of shelf-life for
      frozen drug products involves the estimation of drug shelf-lives at different
      temperatures, which requires multiple phase linear regression. Mellon suggested
      obtaining a combined shelf-life by determining shelf-lives based on data
      available at different temperatures. This method, however, does not account for
      the fact that the shelf-life at the second-phase would depend on the shelf-life
      at the first phase. As an alternative, we propose a method for determination of
      drug shelf-lives for the two phases using a two-phase regression analysis based
      on the statistical principle described in the FDA guideline and the ICH
      guideline. A numerical example is presented to illustrate the proposed method.

PMID- 11304740
TI  - Variance estimation of a survival function for interval-censored survival data.
AB  - Interval-censored survival data often occur in medical studies, especially in
      clinical trials. In this case, many authors have considered estimation of a
      survival function. There is, however, relatively little discussion on estimating
      the variance of estimated survival functions. For right-censored data, a special
      case of interval-censored data, the most commonly used method for variance
      estimation is to use the Greenwood formula. In this paper we propose a
      generalization of the Greenwood formula for variance estimation of a survival
      function based on interval-censored data. Also a simple bootstrap approach is
      presented. The two methods are evaluated and compared using simulation studies
      and a real data set. The simulation results suggest that the methods work well.

PMID- 11304741
TI  - Worm plot: a simple diagnostic device for modelling growth reference curves.
AB  - The worm plot visualizes differences between two distributions, conditional on
      the values of a covariate. Though the worm plot is a general diagnostic tool for
      the analysis of residuals, this paper focuses on an application in constructing
      growth reference curves, where the covariate of interest is age. The LMS model of
      Cole and Green is used to construct reference curves in the Fourth Dutch Growth
      Study 1997. If the model fits, the measurements in the reference sample follow a
      standard normal distribution on all ages after a suitably chosen Box-Cox
      transformation. The coefficients of this transformation are modelled as smooth
      age-dependent parameter curves for the median, variation and skewness,
      respectively. The major modelling task is to choose the appropriate amount of
      smoothness of each parameter curve. The worm plot assesses the age-conditional
      normality of the transformed data under a variety of LMS models. The fit of each
      parameter curve is closely related to particular features in the worm plot,
      namely its offset, slope and curvature. Application of the worm plot to the Dutch
      growth data resulted in satisfactory reference curves for a variety of
      anthropometric measures. It was found that the LMS method generally models the
      age-conditional mean and skewness better than the age-related deviation and
      kurtosis.

PMID- 11304742
TI  - Statistical cost-effectiveness analysis of two treatments based on net health
      benefits.
AB  - Statistical methods for cost-effectiveness analysis (CEA) for two treatments that
      mimic the deterministic optimal rules of CEA are presented. In these rules the
      objective is to determine the treatment with the maximal effectiveness whose unit
      cost is less than an amount, lambda, that a decision-maker is willing to pay
      (WTP). This is accomplished by identifying the treatment with the largest
      positive net health benefit (NHB), which is a function of lambda, while
      controlling the familywise error rate both when the WTP value is given and when
      it is unspecified. Fieller's theorem is used to determine a region of WTP values
      where the NHBs of the treatments are not distinguishable. For each lambda outside
      of the confidence region, the larger treatment is identified. A newly developed
      one-tailed analogue of Fieller's theorem is used to determine the WTP values
      where a treatment's NHB is positive. The situation in which both treatments are
      experimental is distinguished from the case where one of the treatments is usual
      care. The one-tailed confidence region is used in the latter case to obtain the
      lambda values where the NHBs are not different, and determining the region of
      positivity of the NHBs may be unnecessary. An example is presented in which the
      cost-effectiveness of two antipsychotic treatments is evaluated.

PMID- 11304743
TI  - Aquatic prey capture in ray-finned fishes: a century of progress and new
      directions.
AB  - The head of ray-finned fishes is structurally complex and is composed of numerous
      bony, muscular, and ligamentous elements capable of intricate movement. Nearly
      two centuries of research have been devoted to understanding the function of this
      cranial musculoskeletal system during prey capture in the dense and viscous
      aquatic medium. Most fishes generate some amount of inertial suction to capture
      prey in water. In this overview we trace the history of functional morphological
      analyses of suction feeding in ray-finned fishes, with a particular focus on the
      mechanisms by which suction is generated, and present new data using a novel flow
      imaging technique that enables quantification of the water flow field into the
      mouth. We begin with a brief overview of studies of cranial anatomy and then
      summarize progress on understanding function as new information was brought to
      light by the application of various forms of technology, including high-speed
      cinematography and video, pressure, impedance, and bone strain measurement. We
      also provide data from a new technique, digital particle image velocimetry (DPIV)
      that allows us to quantify patterns of flow into the mouth. We believe that there
      are three general areas in which future progress needs to occur. First,
      quantitative three-dimensional studies of buccal and opercular cavity dimensions
      during prey capture are needed; sonomicrometry and endoscopy are techniques
      likely to yield these data. Second, a thorough quantitative analysis of the flow
      field into the mouth during prey capture is necessary to understand the effect of
      head movement on water in the vicinity of the prey; three-dimensional DPIV
      analyses will help to provide these data. Third, a more precise understanding of
      the fitness effects of structural and functional variables in the head coupled
      with rigorous statistical analyses will allow us to better understand the
      evolutionary consequences of intra- and interspecific variation in cranial
      morphology and function.

PMID- 11304744
TI  - Evolution and mechanics of long jaws in butterflyfishes (family Chaetodontidae).
AB  - We analyzed the functional morphology and evolution of the long jaws found in
      several butterflyfishes. We used a conservative reanalysis of an existing
      morphological dataset to generate a phylogeny that guided our selection of seven
      short- and long-jawed taxa in which to investigate the functional anatomy of the
      head and jaws: Chaetodon xanthurus, Prognathodes falcifer (formerly Chaetodon
      falcifer), Chelmon rostratus, Heniochus acuminatus, Johnrandallia nigrirostris,
      Forcipiger flavissimus, and F. longirostris. We used manipulations of fresh,
      preserved, and cleared and stained specimens to develop mechanical diagrams of
      how the jaws might be protruded or depressed. Species differed based on the
      number of joints within the suspensorium. We used high-speed video analysis of
      five of the seven species (C. xanthurus, Chel. rostratus, H. acuminatus, F.
      flavissimus, and F. longirostris) to test our predictions based on the mechanical
      diagrams: two suspensorial joints should facilitate purely anteriorly directed
      protrusion of the lower jaw, one joint should allow less anterior protrusion and
      result in more depression of the lower jaw, and no joints in the suspensorium
      should constrain the lower jaw to simple ventral rotation around the jaw joint,
      as seen in generalized perciform fishes. We found that the longest-jawed species,
      F. longirostris, was able to protrude its jaws in a predominantly anterior
      direction and further than any other species. This was achieved with little input
      from cranial elevation, the principal input for other known lower jaw protruders,
      and is hypothesized to be facilitated by separate modifications to the
      sternohyoideus mechanism and to the adductor arcus palatini muscle. In F.
      longirostris the adductor arcus palatini muscle has fibers oriented
      anteroposteriorly rather than medial-laterally, as seen in most other perciforms
      and in the other butterflyfish studied. These fibers are oriented such that they
      could rotate the ventral portion of the quadrate anteriorly, thus projecting the
      lower jaw anteriorly. The intermediate species lack modification of the adductor
      arcus palatini and do not protrude their jaws as far (in the case of F.
      flavissimus) or in a purely anterior fashion (in the case of Chel. rostratus).
      The short-jawed species both exhibit only ventral rotation of the lower jaw,
      despite the fact that H. acuminatus is closely related to Forcipiger.

PMID- 11304745
TI  - Ultrastructure of the hindgut of Drosophila larvae, with special reference to the
      domains identified by specific gene expression patterns.
AB  - The hindgut of Drosophila larvae consists of nine domains that have been
      distinguished by specific gene expression patterns. In the present study, we
      examined the ultrastructure of the hindgut of Drosophila larvae, with special
      reference to the domains, in order to determine whether or not the domains are
      morphologically distinct functional units. Each domain showed specific
      ultrastructural features that suggested specific corresponding functions.
      According to the morphological features, terms are proposed for each domain: the
      imaginal ring; the "pylorus," which has a thick cuticular layer and well
      developed sphincter muscles; the "large intestine," which occupies a major middle
      portion of the hindgut and has a unique dorsal and ventral subdivision; "border
      cells," which delineate the anterior and posterior borders of the large intestine
      and the border between the dorsal and ventral domains of the large intestine; and
      the "rectum," which is situated at the posterior end of the hindgut and has a
      thick cuticular layer and sphincter muscles. The morphological features indicate
      that the large intestine has active absorptive activities. The domains, which
      have been distinguished by gene expressions, were demonstrated to be functional
      tissue units of the gut.

PMID- 11304746
TI  - Limb and tail lengths in relation to substrate usage in Tropidurus lizards.
AB  - A close relationship between morphology and habitat is well documented for
      anoline lizards. To test the generality of this relationship in lizards, snout
      vent, tail, and limb lengths of 18 species of Tropidurus (Tropiduridae) were
      measured and comparisons made between body proportions and substrate usage.
      Phylogenetic analysis of covariance by computer simulation suggests that the
      three species inhabiting sandy soils have relatively longer feet than do other
      species. Phylogenetic ANCOVA also demonstrates that the three species inhabiting
      tree canopies and locomoting on small branches have short tails and hind limbs.
      These three species constitute a single subclade within the overall Tropidurus
      phylogeny and analyses with independent contrasts indicate that divergence in
      relative tail and hind limb length has been rapid since they split from their
      sister clade. Being restricted to a single subclade, the difference in body
      proportions could logically be interpreted as either an adaptation to the clade's
      lifestyle or simply a nonadaptive synapomorphy for this lineage. Nevertheless,
      previous comparative studies of another clade of lizards (Anolis) as well as
      experimental studies of Sceloporus lizards sprinting on rods of different
      diameters support the adaptive interpretation.

PMID- 11304747
TI  - Microscopic anatomy of the eye of the deep-diving Antarctic Weddell seal
      (Leptonychotes weddellii).
AB  - The microscopic anatomy of the eye of the Weddell seal was studied with various
      light and electron microscopic methods with a view to correlating morphological
      findings with the biology of this seal which is adapted to the extremes of the
      Antarctic environment and to extreme diving excursions into the lightless depths
      of the sea. In the retina an area centralis was found but no fovea centralis. The
      densely packed photoreceptors consist exclusively of highly differentiated rods,
      which in primates detect light at low intensity but have rather poor image
      discrimination. The ganglion cells are relatively scarce, suggesting a high
      degree of convergence of the light-sensitive cells on the ganglion cells. The
      pigment epithelium is almost devoid of pigment granules. The extensive tapetum
      lucidum is about 400-500 microm thick and is composed of about 30 layers of
      specialized cells. The cornea is 650 (center) to 800-900 (periphery) microm
      thick. Its structure and glycosaminoglycan histochemistry correspond to that of
      other mammals. The iridocorneal angle is unusually deep and pervaded by an
      elaborate trabecular meshwork, which together with a complex canal of Schlemm can
      be correlated with the ability to absorb large amounts of fluid. The ciliary
      muscle and its antagonist, the membrane of Bruch, are poorly developed,
      suggesting relatively poor abilities of accommodation. The combination of a well
      developed tapetum lucidum, an unpigmented pigment epithelium, well-developed
      rods, and a high number of rods converging on only few ganglion cells is
      obviously an adaptation to an extreme light sensitivity, enabling the animals to
      make use of the little light available in the deep sea.

PMID- 11304748
TI  - Neurotransmitters regulating acid secretion in the proventriculus of the Houbara
      bustard (Chlamydotis undulata): a morphological viewpoint.
AB  - Endocrine cells containing somatostatin (Som), gastrin-releasing peptide (GRP),
      and neuronal nitric oxide synthase (nNOS) and nerve fibers containing choline
      acetyl transferase (ChAT), tyrosine hydroxylase (TH), galanin (Gal), substance P
      (SP), and vasoactive intestinal polypeptide (VIP) were immunolocalized in the
      proventriculus of the Houbara bustard, Chlamydotis undulata. While GRP
      immunoreactive (GRP-IR) cells occur in the inner zone, somatostatin (Som-IR) and
      polyclonal nNOS (nNOS-IR) immunoreactive cells were localized mainly in the
      peripheral zone of submucosal glands. GRP-IR, Som-IR, and nNOS-IR cells were
      occasionally observed in the walls of the gastric glands. Endocrine cells are of
      the closed variety and usually possess apical processes extending along the basal
      surfaces of adjacent nonreactive cells. Ultrastructural features of these cells
      are typical. ChAT, Gal, SP, VIP, and TH were immunolocalized in nerve fibers and
      terminals in the walls of arterioles and capillaries at the periphery of
      submucosal glands. Immunoreactivity to monoclonal nNOS occurred mainly in
      neuronal cell bodies in ganglia located around the submucosal glands. ChAT and TH
      immunoreactive cell bodies were also occasionally seen around the submucosal
      glands in the peripheral region. Immunoreactivity to Gal, SP, and VIP, but not
      ChAT or TH, was discernible around the walls of gastric glands. It was concluded
      that the distribution of neurotransmitters in neuronal structures is similar, but
      that of the endocrine cells varies from that of some avian species. The roles of
      these neurotransmitters in the regulation of acid secretion are discussed.

PMID- 11304749
TI  - Comparative study of the cuticle in some aquatic oligochaetes (Annelida:
      Clitellata).
AB  - An examination of the cuticle of six aquatic oligochaete species using
      transmission electron microscopy revealed a larger morphological variation than
      previously known. Three freshwater species, Aulodrilus pluriseta, Spirosperma
      ferox (both Tubificidae), and Pristina breviseta (Naididae), and three marine
      species, Clitellio arenarius, Heterochaeta costata (both Tubificidae), and
      Paranais litoralis (Naididae), were investigated. The arrangement of the collagen
      fibers in the cuticle differs among the studied species. Only S. ferox shows an
      "orthogonal grid," i.e., layers of parallel fibers perpendicular to each other,
      as earlier described for lumbricids and enchytraeids. Clitellio arenarius and H.
      costata have fibers arranged in layers, while A. pluriseta and P. litoralis have
      irregularly distributed fibers. Pristina breviseta lacks cuticular fibers. The
      matrix surrounding the collagen fibers (when present) continues outside the fiber
      layer, making up a thin epicuticle, which has a unique banding in each of the
      studied species. The external surface of the epicuticle is covered with
      epicuticular projections. Their number, shape, and attachment to the epicuticle
      vary among the studied species. Furthermore, a distinctive internal substructure
      of the projections was observed in H. costata, A. pluriseta, S. ferox, and P.
      breviseta. Microvilli, extensions from the epidermal cells, penetrate the cuticle
      and terminate at its outer surface. In three species microvilli were observed to
      pinch off the epicuticular projections. The size, number, and shape of the latter
      vary; no typical microvilli were observed in S. ferox.

PMID- 11304750
TI  - Alkaline phosphatase activity in whitefly salivary glands and saliva.
AB  - Alkaline phosphatase activity was histochemically localized in adult whiteflies
      (Bemisia tabaci B biotype, syn. B. argentifolii) with a chromogenic substrate (5
      bromo-4-chloro-3-indolylphosphate) and a fluorogenic substrate (ELF-97). The
      greatest amount of staining was in the basal regions of adult salivary glands
      with additional activity traced into the connecting salivary ducts. Other tissues
      that had alkaline phosphatase activity were the accessory salivary glands, the
      midgut, the portion of the ovariole surrounding the terminal oocyte, and the
      colleterial gland. Whitefly nymphs had activity in salivary ducts, whereas
      activity was not detected in two aphid species (Rhodobium porosum and Aphis
      gossypii). Whitefly diet (15% sucrose) was collected from whitefly feeding
      chambers and found to have alkaline phosphatase activity, indicating the enzyme
      was secreted in saliva. Further studies with salivary alkaline phosphatase
      collected from diet indicated that the enzyme had a pH optimum of 10.4 and was
      inhibited by 1 mM cysteine and to a lesser extent 1 mM histidine. Dithiothreitol,
      inorganic phosphate, and ethylenediaminetetraacetic acid (EDTA) also inhibited
      activity, whereas levamisole only partially inhibited salivary alkaline
      phosphatase. The enzyme was heat tolerant and retained approximately 50% activity
      after a 1-h treatment at 65 degrees C. The amount of alkaline phosphatase
      activity secreted by whiteflies increased under conditions that stimulate
      increased feeding. These observations indicate alkaline phosphatase may play a
      role during whitefly feeding.

PMID- 11304751
TI  - Male accessory gland derived factors can stimulate oogenesis and enhance
      oviposition in Helicoverpa armigera (Lepidoptera: Noctuidae).
AB  - In Helicoverpa armigera, female moths began to lay eggs on the third day after
      emergence. Mating stimulated earlier egg maturation/oogenesis (P = 0.002) and
      oviposition (P << 0.01). We established a suitable bioassay model for the
      influence of male accessory glands (MAG) on the physiology of virgin females:
      Crude extracts of MAG (2- to 3-day-old) were injected into 2-day-old virgin
      females, and the injected females were dissected 20 h after mating. It was shown
      that crude extracts of MAG stimulated earlier egg maturation (P < 0.001) and
      oviposition (the oviposition ratio was more than 2 times the ratio of the
      control). Proteinaceous components in crude extracts purified by fractionation
      and sub-fractionation in reverse phase high performance liquid chromatography
      also stimulated earlier egg maturation (P < 0.01) and ovipositon (more than 2
      times the ratio of the control), and we called them the oogenesis and ovipostion
      factors (OOSF). With SDS-PAGE, the molecular mass of the bands from OOSF was
      estimated to be between 55-66 KD. Arch.

PMID- 11304752
TI  - Isolation and partial characterization of gypsy moth BTR-270, an anionic brush
      border membrane glycoconjugate that binds Bacillus thuringiensis Cry1A toxins
      with high affinity.
AB  - BTR-270, a gypsy moth (Lymantria dispar) brush border membrane molecule that
      binds Bacillus thuringiensis (Bt) Cry1A toxins with high affinity, was purified
      by preparative gel electrophoresis. Rabbit antibodies specific for the Bt toxin
      binding molecule were raised. Attempts to label BTR-270 by protein-directed
      techniques were futile, but it was degraded by proteases with broad specificity
      indicating the presence of a peptide. Carbohydrate was detected by labeling with
      digoxigenin hydrazide following periodate oxidation. Mild alkaline hydrolysis
      destroyed toxin and antibody binding, suggesting O-linked glycans are involved in
      the activity. GC/MS composition analysis showed that the predominant sugars were
      galactose, glucose, and N-acetyl galactosamine with lesser amounts of N-acetyl
      glucosamine, glucuronic acid, xylose, and fucose. The carbohydrate moiety
      accounted for 73% of its total mass. Amino acid analysis showed a high content of
      aspartic/asparagine, threonine, and serine residues in the protein moiety. The
      purified glycoconjugate was not visualized using Coomassie or silver staining
      procedures, but stained "blue" using the cationic dye Stains-all. BTR-270 was
      labeled with biotin and used as a diagnostic probe for screening and identifying
      toxins that bind to the receptor. Toxin-binding kinetics obtained using a
      biosensor demonstrated that the receptor binds Cry1Aa and Cry1Ab toxins with high
      affinity, and displays a weaker affinity for Cry1Ac, in correlation with the
      toxicity of these toxins towards gypsy moth. Arch.

PMID- 11304753
TI  - Evaluation of PET ligands (+)N-[(11)C]ethyl-3-piperidyl benzilate and (+)N
      [(11)C]propyl-3-piperidyl benzilate for muscarinic cholinergic receptors: a PET
      study with microdialysis in comparison with (+)N-[(11)C]methyl-3-piperidyl
      benzilate in the conscious monkey brain.
AB  - We developed PET ligands (+)N-[(11)C]ethyl-3-piperidyl benzilate ([(11)C](+)3
      EPB) and (+)N-[(11)C]propyl-3-piperidyl benzilate ([(11)C](+)3-PPB) for cerebral
      muscarinic cholinergic receptors. The distribution and kinetics of the novel
      ligands were evaluated for comparison with the previously reported ligand (+)N
      [(11)C]methyl-3-piperidyl benzilate ([(11)C](+)3-MPB) in the monkey brain (Macaca
      mulatta) in the conscious state using high-resolution positron emission
      tomography (PET). At 60-91 min postinjection, regional distribution patterns of
      these three ligands were almost identical, and were consistent with the
      muscarinic receptor density in the brain as previously reported in vitro.
      However, the time-activity curves of [(11)C](+)3-EPB and [(11)C](+)3-PPB showed
      earlier peak times of radioactivity and a faster clearance rate than [(11)C](+)3
      MPB in cortical regions rich in the receptors. Kinetic analysis using the three
      compartment model with time-activity curves of radioactivity in metabolite
      corrected arterial plasma as input functions revealed that labeling with longer
      [(11)C]alkyl chain length induced lower binding potential (BP = k(3)/k(4)),
      consistent with the rank order of affinity of these ligands obtained by an in
      vitro assay using rat brain slices and [(3)H]QNB. The cholinesterase inhibitor
      Aricept administered at doses of 50 and 250 microg/kg increased acetylcholine
      level in extracellular fluid of the frontal cortex and the binding of [(11)C](+)3
      PPB with the lowest affinity to the receptors was displaced by the endogenous
      acetylcholine induced by cholinesterase inhibition, while [(11)C](+)3-MPB with
      the highest affinity was not significantly affected. Taken together, these
      observations indicate that the increase in [(11)C]alkyl chain length could alter
      the kinetic properties of conventional receptor ligands for PET by reducing the
      affinity to receptors, which might make it possible to assess the interaction
      between endogenous neurotransmitters and ligand-receptor binding in vivo as
      measured by PET.

PMID- 11304754
TI  - Effects of aging on serotonin transporter availability and its response to
      fluvoxamine in the living brain: PET study with [(11)C](+)McN5652 and [(11)C](
      )McN5652 in conscious monkeys.
AB  - Age-related changes in the serotonin transporter (SERT) in the living brains of
      conscious young (5.9 +/- 1.8 years old) and aged (19.0 +/- 3.3 years old) monkeys
      (Macaca mulatta) were evaluated in combination with [(11)C](+)McN5652 and its
      inactive enantiomer [(11)C](-)McN5652 by high-resolution positron emission
      tomography (PET). For the quantitative analysis of SERT binding in vivo, two
      serial PET scans with [(11)C](+)McN5652 and [(11)C](-)McN5652 were performed in
      the same animals in a day and the differences in radioactivities of
      [(11)C](+)McN5652 vs. [(11)C](-)McN5652 measured from 41-91 min postinjection
      were calculated as an estimate of specific ligand binding. Higher specific
      binding of SERT was observed in the thalamus and striatum, regions known to
      contain high densities of SERT by in vitro assay, with intermediate levels in the
      pons, hippocampus, cingulate gyrus, and cortical regions and lower levels in the
      cerebellum in both young and aged monkeys. Almost all regions assayed except the
      cerebellum showed significant age-related decreases in the specific binding of
      SERT, which showed reverse correlation with cortisol level in plasma. When the
      SERT blocker fluvoxamine (1 mg/kg) was administered intravenously 30 min after
      tracer injection, specific binding of SERT was displaced in both age groups.
      However, the degree of displacement was more marked in young than in aged
      monkeys. Cortisol level in plasma was significantly higher in aged than in young
      animals. These observations demonstrate the usefulness of the combined use of
      [(11)C](+)McN5652 and [(11)C](-)McN5652 as an indicator for the age-related
      changes in cortical SERT measured noninvasively by PET. In addition, these
      observations suggest that the age-related impairment of SERT sensitivity for
      fluvoxamine might be related to the reduced efficacy of antidepressant therapy in
      elderly patients with depression.

PMID- 11304755
TI  - Stress, hippocampal plasticity, and spatial learning.
AB  - During the last two decades numerous studies have been conducted in an attempt to
      correlate the mechanisms of long-term potentiation (LTP) of hippocampal synaptic
      transmission with those required for spatial memory formation in the hippocampus.
      Because stressful events block the induction of hippocampal LTP, it has been
      suggested that deficits in spatial learning following stress may be related to
      suppression of LTP-like phenomena in the hippocampus. Here I review these studies
      and discuss them in light of the emerging view that stress may induce changes in
      thresholds for synaptic plasticity necessary for both LTP induction and spatial
      memory formation. This phenomenon, known as metaplasticity, may involve a
      glucocorticoid modulation of calcium homeostasis.

PMID- 11304756
TI  - Vesicular acetylcholine transporter in the rat nucleus accumbens shell:
      subcellular distribution and association with mu-opioid receptors.
AB  - Cholinergic interneurons in the nucleus accumbens shell (AcbSh) are implicated in
      the reinforcing behaviors that develop in response to opiates active at mu-opioid
      receptors (MOR). We examined the electron microscopic immunocytochemical
      localization of the vesicular acetylcholine transporter (VAChT) and MOR to
      determine the functional sites for storage and release of acetylcholine (ACh),
      and potential interactions involving MOR in this region of rat brain. VAChT was
      primarily localized to membranes of small synaptic vesicles in axon terminals.
      Less than 10% of the VAChT-labeled terminals were MOR-immunoreactive. In
      contrast, 35% of the cholinergic terminals formed symmetric or punctate synapses
      with dendrites showing an extrasynaptic plasmalemmal distribution of MOR.
      Membranes of tubulovesicles in other selective dendrites were also VAChT-labeled,
      and almost half of these dendrites displayed plasmalemmal MOR immunoreactivity.
      The VAChT-labeled dendritic tubulovesicles often apposed unlabeled axon terminals
      that formed symmetric synapses. Our results indicate that in the AcbSh MOR
      agonists can modulate the release of ACh from vesicular storage sites in axon
      terminals as well as in dendrites where the released ACh may serve an
      autoregulatory function involving inhibitory afferents. These results also
      suggest, however, that many of the dendrites of spiny projection neurons in the
      AcbSh are dually influenced by ACh and opiates active at MOR, thus providing a
      cellular substrate for ACh in the reinforcement of opiates.

PMID- 11304757
TI  - [(18)F]FDOPA and [(18)F]CFT are both sensitive PET markers to detect presynaptic
      dopaminergic hypofunction in early Parkinson's disease.
AB  - The aim of this study was to compare two PET ligands, 6-[(18)F]fluoro-L-dopa
      ([(18)F]FDOPA) and (18)F-labeled CFT, 2beta-carbomethoxy-3beta-(4-[(18)F]
      fluorophenyl)tropane ([(18)F]CFT), in detecting presynaptic dopaminergic
      hypofunction in early Parkinson's disease (PD). These ligands reflect different
      aspects of presynaptic dopaminergic function, since [(18)F]FDOPA mainly reflects
      6-[(18)F]fluorodopamine (fluorodopamine) synthesis and storage whereas [(18)F]CFT
      uptake is related to dopamine transporter function. Eight de novo patients with
      PD who had never been on antiparkinsonian medication were investigated with
      [(18)F]FDOPA and [(18)F]CFT PET. Five healthy volunteers were studied as
      controls. In PD patients, both [(18)F]FDOPA and [(18)F]CFT uptakes were
      significantly reduced both in the contralateral and ipsilateral anterior and
      posterior putamen. The reduction was greatest in the contralateral posterior
      putamen (to 28% of control mean for [(18)F]FDOPA, P < 0.0001 and to 16% for
      [(18)F]CFT, P < 0.0001). Individually, all patients' [(18)F]FDOPA and [(18)F]CFT
      uptake values in the contralateral anterior and posterior putamen were below 3 SD
      of the control mean. In the caudate nucleus, the mean uptake of both tracers was
      significantly reduced both ipsilaterally and contralaterally, but less severely
      than in the putamen (to 69% of the control mean for [(18)F]FDOPA, P = 0.003 and
      to 60% for [(18)F]CFT, P = 0.001 contralaterally). Our results show that both
      [(18)F]FDOPA as well as [(18)F]CFT sensitively detect presynaptic dopaminergic
      hypofunction in early PD. They demonstrate a considerable reduction of tracer
      uptake that is greatest in the posterior putamen, followed by the anterior
      putamen and the caudate nucleus.

PMID- 11304758
TI  - Differential distribution of cAMP-specific phosphodiesterase 7A mRNA in rat brain
      and peripheral organs.
AB  - We investigated the regional distribution and cellular localization of mRNA
      coding for the cAMP-specific phosphodiesterase 7A (PDE7A) in rat brain and
      several peripheral organs by in situ hybridization histochemistry. The regional
      expression of two splice variants, PDE7A1 and PDE7A2, was examined by RT-PCR
      using RNA extracted from several brain regions. PDE7A mRNA was found to be widely
      distributed in rat brain in both neuronal and nonneuronal cell populations. The
      highest levels of hybridization were observed in the olfactory bulb, olfactory
      tubercle, hippocampus, cerebellum, medial habenula nucleus, pineal gland, area
      postrema, and choroid plexus. Positive hybridization signals were also detected
      in other areas, such as raphe nuclei, temporal and entorhinal cortex, pontine
      nuclei, and some cranial nerve motor nuclei. Both mRNA splice forms were
      differentially distributed in several areas of the brain with the striatum
      expressing only PDE7A1 and the olfactory bulb and spinal cord expressing PDE7A2
      exclusively. In peripheral organs the highest levels of PDE7A hybridization were
      seen in kidney medulla, although testis, liver, adrenal glands, thymus, and
      spleen also presented high hybridization signal. These results are consistent
      with PDE7A being involved in the regulation of cAMP signaling in many brain
      functions. The consistent colocalization with PDE4 mRNAs suggests that PDE7A
      could have an effect on memory, depression, and emesis. The results offer clear
      anatomical and functional systems in which to investigate future specific PDE7
      inhibitors.

PMID- 11304759
TI  - Entopeduncular lesions facilitate and thalamic lesions depress spontaneous and
      drug-evoked motor behavior in the hemiparkinsonian rat.
AB  - Pallidotomy is a neurosurgical procedure designed to ameliorate the akinesia and
      bradykinesia associated with Parkinson's disease. In the present study, the
      effects of pallidal-like lesions on motor behavior in the hemiparkinsonian rat
      were compared to the effects of lesions in the ventrolateral thalamus, a target
      of entopeduncular projections feeding motor-related information to motor cortex.
      Six aspects of spontaneous and evoked behavior induced by amphetamine and
      apomorphine in the hemiparkinsonian rat with either bilateral electrolytic
      entopeduncular lesions or bilateral electrolytic ventrolateral thalamic lesions
      were measured for 60 min. Saline or amphetamine, 5 mg/kg, or apomorphine, 0.3
      mg/kg, were administered IP 5 min before the tests. The results show that on all
      measures except time spent resting the hemiparkinsonian rats with the
      entopeduncular lesions were more active than the hemiparkinsonian rats with the
      thalamic lesions. The asymmetrical rotation responses to dopamine receptor
      stimulation evoked by amphetamine and apomorphine were influenced by the general
      effect on gross motor behavior, as shown by the response being very large in the
      entopeduncular group and very small in the thalamic group. These results are
      consistent with current thinking about the functional organization of the basal
      ganglia according to which damage of the entopeduncular nucleus reduces its
      inhibitory control of the thalamic motor regions, thereby promoting thalamic
      facilitation of motor cortex, and damage to the thalamic motor regions has the
      opposite effect. These effects of the lesions translate, respectively, into
      hyperactivity and hypoactivity without blocking the asymmetrical rotation
      response of the hemiparkinsonian rat.

PMID- 11304760
TI  - Effect of MPTP-induced denervation on basal ganglia GABA(B) receptors:
      correlation with dopamine concentrations and dopamine transporter.
AB  - We investigated the effect of MPTP-induced lesion of the substantia nigra pars
      compacta (SNpc) dopaminergic neurons on GABA(B) receptors in the basal ganglia of
      mice and monkeys using receptor autoradiography and in situ hybridization. The
      extent of the lesion was measured with striatal catecholamine content, striatal
      binding of (125)I-RTI-121 to dopamine transporter (DAT), and DAT expression in
      the SNpc. GABA(B) receptors in mice brain were evaluated using (3)H-CGP54626 and
      its expression was measured with oligonucleotides probes targeting the mRNAs of
      GABA(B(1a+b)), GABA(B(1a)), GABA(B(1b)), GABA(B(2)) subunits. In monkeys, (125)I
      CGP64213 and selective probes for GABA(B(1a+b)) and GABA(B(2)) mRNAs were used.
      In mice, dopamine content, (125)I-RTI-121 binding, and DAT expression were
      reduced by 44%, 40%, and 39% after a dose of 40 mg/kg of MPTP and 74%, 70%, and
      34% after 120 mg/kg of MPTP, respectively. In monkeys, dopamine content and DAT
      expression were decreased by more than 90% and 80%, respectively. In the striatum
      and the subthalamic nucleus, GABA(B) receptors were unchanged following MPTP in
      both species. In the SNpc of mice, MPTP (120 mg/kg) induced a significant
      decrease of (3)H-CGP54626 binding (-10%) and of the expression of GABA(B(1a+b))
      mRNA (-13%). The decrease of the expression of GABA(B(1a+b)) mRNA was correlated
      with dopamine content, (125)I-RTI-121 binding and DAT expression. In MPTP-treated
      monkeys, (125)I-CGP64213 binding (-40%), GABA(B(1a+b)) mRNA (-69%) and GABA(B(2))
      mRNA (-66%) were also significantly decreased in the SNpc. Our results suggest
      that MPTP-induced denervation is associated with a decrease of GABA(B) receptors
      restricted to the SNpc. These observations may be relevant to the pathophysiology
      of motor disorders involving dysfunction of the basal ganglia such as Parkinson
      disease.

PMID- 11304761
TI  - Mapping of CNS sigma(1) receptors in the conscious monkey: preliminary PET study
      with [(11)C]SA4503.

PMID- 11304762
TI  - Does palliative care palliate?

PMID- 11304763
TI  - Topotecan versus observation after cisplatin plus etoposide in extensive-stage
      small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative
      Oncology Group.
AB  - PURPOSE: To determine the efficacy of topotecan in combination with standard
      chemotherapy in previously untreated patients with extensive-stage small-cell
      lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) conducted a
      phase III trial. PATIENTS AND METHODS: Eligible patients had measurable or
      assessable disease and an ECOG performance status of 0 to 2; stable brain
      metastases were allowed. All patients received four cycles of cisplatin and
      etoposide every 3 weeks (step 1; PE). Patients with stable or responding disease
      were then randomized to observation or four cycles of topotecan (1.5 mg/m(2)/d
      for 5 days, every 3 weeks; step 2). A total of 402 eligible patients were
      registered to step 1, and 223 eligible patients were registered to step 2
      (observation, n = 111; topotecan, n = 112). RESULTS: Complete and partial
      response rates to induction PE were 3% and 32%, respectively. A 7% response rate
      was observed with topotecan (complete response, 2%; partial response, 5%). The
      median survival time for all 402 eligible patients was 9.6 months. Progression
      free survival (PFS) from date of randomization on step 2 was significantly better
      with topotecan compared with observation (3.6 months v 2.3 months; P <.001).
      However, overall survival from date of randomization on step 2 was not
      significantly different between the observation and topotecan arms (8.9 months v
      9.3 months; P =.43). Grade 4 neutropenia and thrombocytopenia occurred in 50% and
      3%, respectively, of PE patients in step 1 and 60% and 13% of topotecan patients
      in step 2. Grade 4/5 infection was observed in 4.6% of PE patients and 1.8% of
      topotecan patients. Grade 3/4 anemia developed in 22% of patients who received
      topotecan. No difference in quality of life between topotecan and observation was
      observed at any assessment time or for any of the subscale scores. CONCLUSION:
      Four cycles of PE induction therapy followed by four cycles of topotecan improved
      PFS but failed to improve overall survival or quality of life in extensive-stage
      SCLC. Four cycles of standard PE remains an appropriate first-line treatment for
      extensive-stage SCLC patients with good performance status.

PMID- 11304764
TI  - Prospective study on quality of life before and after radical radiotherapy in non
      small-cell lung cancer.
AB  - PURPOSE: The purpose of this study was to investigate changes in respiratory
      symptoms and quality of life (QoL) in patients with non-small-cell lung cancer
      (NSCLC) receiving radical radiotherapy (60 Gy). Additionally, the association
      between the level of symptom relief and objective tumor response, as well as with
      radiation-induced pulmonary changes, was investigated. PATIENTS AND METHODS: One
      hundred sixty-four patients were entered onto this prospective study. The
      European Organization for Research and Treatment of Cancer (EORTC) Quality of
      Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 were used to investigate changes
      in QOL: Assessments were performed before radiotherapy and 2 weeks, 6 weeks, 3
      months, 6 months, and 12 months after the completion of radiotherapy. RESULTS:
      The QoL response rates were excellent for hemoptysis (83%); good for chest pain
      (68%), arm/shoulder pain (63%), and appetite loss (60%); and poor for dyspnea
      (37%), cough (31%), and fatigue (28%). The QoL response rates for the five
      functioning scales of the QLQ-C30 varied from 35% for physical and role
      functioning to 55% for social and cognitive functioning. The response rate for
      global QoL was 36%. A significant association was found between tumor response
      and palliation of chest pain, arm/shoulder pain, and physical functioning. During
      radiotherapy, a significant increase for most general symptoms and a
      deterioration in functioning and QoL were noted. CONCLUSION: This study is the
      first to describe palliation and changes in QoL in radically irradiated patients
      with NSCLC. Radical radiotherapy offers palliation of respiratory symptoms and
      improved QoL in a substantial proportion of patients with NSCLC who have
      relatively good prognostic features. Although tumor reduction is associated with
      palliation of respiratory symptoms, it cannot serve as a surrogate for
      palliation.

PMID- 11304765
TI  - Hematopoietic stem-cell transplantation for treatment-related leukemia or
      myelodysplasia.
AB  - PURPOSE: This report describes results of related or unrelated hematopoietic stem
      cell transplants in 111 patients with treatment-related leukemia or
      myelodysplasia performed consecutively at the Fred Hutchinson Cancer Research
      Center between December 1971 and June 1998, and identifies patient and treatment
      characteristics associated with survival and relapse. PATIENTS AND METHODS: At
      transplantation, 56 patients had treatment-related secondary acute myeloid
      leukemia (AML), 15 had refractory anemia with excess blasts in transition (RAEB
      T), 23 had refractory anemia with excess blasts (RAEB), 15 had refractory anemia
      (RA), and two had refractory anemia with ringed sideroblasts (RARS). Conditioning
      regimens were total-body irradiation (TBI) and chemotherapy for 60 patients,
      busulfan (BU) 14 to 16 mg/kg and cyclophosphamide (CY) 120 mg/kg (BUCY) for 27
      patients, BU targeted to 600 to 900 ng/mL plasma steady-state concentration with
      120 mg/kg CY (BUCY-t) for 22 patients, and miscellaneous chemotherapy for two
      patients. The donors were HLA-identical or partially identical family members for
      69 patients and unrelated donors for 42 patients. RESULTS: The 5-year disease
      free survival was 8% for TBI, 19% for BUCY, and 30% for BUCY-t (P =.006). The 5
      year cumulative incidence of relapse was 40% for secondary AML, 40% for RAEB-T,
      26% for RAEB, and 0% for RA or RARS (P =.0009). The 5-year cumulative incidence
      of nonrelapse mortality after TBI was 58%; after BUCY, 52%; and after BUCY-t, 42%
      (P =.02). CONCLUSION: Patients at risk for treatment-related leukemia or
      myelodysplasia should be followed closely and be considered for stem-cell
      transplantation early in the course of myelodysplasia using conditioning regimens
      such as BUCY-t designed to reduce nonrelapse mortality.

PMID- 11304766
TI  - Evaluation of the combination of nelarabine and fludarabine in leukemias:
      clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells.
AB  - PURPOSE: A pilot protocol was designed to evaluate the efficacy of fludarabine
      with nelarabine (the prodrug of arabinosylguanine [ara-G]) in patients with
      hematologic malignancies. The cellular pharmacokinetics was investigated to seek
      a relationship between response and accumulation of ara-G triphosphate (ara-GTP)
      in circulating leukemia cells and to evaluate biochemical modulation of cellular
      ara-GTP metabolism by fludarabine triphosphate. PATIENTS AND METHODS: Nine of the
      13 total patients had indolent leukemias, including six whose disease failed
      prior fludarabine therapy. Two patients had T-acute lymphoblastic leukemia, one
      had chronic myelogenous leukemia, and one had mycosis fungoides. Nelarabine (1.2
      g/m(2)) was infused on days 1, 3, and 5. On days 3 and 5, fludarabine (30
      mg/m(2)) was administered 4 hours before the nelarabine infusion. Plasma and
      cellular pharmacokinetic measurements were conducted during the first 5 days.
      RESULTS: Seven patients had a partial or complete response, six of whom had
      indolent leukemias. The disease in four responders had failed prior fludarabine
      therapy. The median peak intracellular concentrations of ara-GTP were
      significantly different (P =.001) in responders (890 micromol/L, n = 6) and
      nonresponders (30 micromol/L, n = 6). Also, there was a direct relationship
      between the peak fludarabine triphosphate and ara-GTP in each patient (r = 0.85).
      The cellular elimination of ara-GTP was slow (median, 35 hours; range, 18 to > 48
      hours). The ratio of ara-GTP to its normal counterpart, deoxyguanosine
      triphosphate, was higher in each patient (median, 42; range, 14 to 1,092) than
      that of fludarabine triphosphate to its normal counterpart, deoxyadenosine
      triphosphate (median, 2.2; range, 0.2 to 27). CONCLUSION: Fludarabine plus
      nelarabine is an effective, well-tolerated regimen against leukemias. Clinical
      responses suggest the need for further exploration of nelarabine against
      fludarabine-refractory diseases. Determination of ara-GTP levels in the target
      tumor population may provide a prognostic test for the activity of nelarabine.

PMID- 11304767
TI  - Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic
      leukemia and small lymphocytic lymphoma demonstrates clinical activity and
      acceptable toxicity.
AB  - PURPOSE: Rituximab has been reported to have little activity in small lymphocytic
      lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with
      significant infusion-related toxicity. This study sought to decrease the initial
      toxicity and optimize the pharmacokinetics with an alternative treatment
      schedule. PATIENTS AND METHODS: Thirty three patients with SLL/CLL received dose
      1 of rituximab (100 mg) over 4 hours. In cohort I (n = 3; 250 mg/m(2)) and cohort
      II (n = 7; 375 mg/m(2)) rituximab was administered on day 3 and thereafter three
      times weekly for 4 weeks using a standard administration schedule. Cohort III (n
      = 23; 375 mg/m(2)) administered rituximab similar to cohort II for the first two
      treatments and then over 1 hour thereafter. RESULTS: A total of 33 CLL/SLL
      patients were enrolled; only one patient discontinued therapy because of infusion
      related toxicity. Thirteen patients developed transient hypoxemia, hypotension,
      or dyspnea that were associated with significant changes in baseline interleukin
      6, interleukin-8, tumor necrosis factor alpha, and interferon gamma compared with
      those not experiencing such reactions. Infusion-related toxicity occurred more
      commonly in older (median age 73 v 62 years; P =.02) patients with no other
      pretreatment clinical or laboratory features predicting occurrence of these
      events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%).
      Median response duration for these 15 patients was 10 months (95% CI, 6.8-13.2;
      range, 3 to 17+). CONCLUSION: Rituximab administered thrice weekly for 4 weeks
      demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related
      events seem to be cytokine mediated and resolve by the third infusion making
      rapid administration possible. Future combination studies of rituximab with other
      therapies in CLL seem warranted.

PMID- 11304768
TI  - Rituximab dose-escalation trial in chronic lymphocytic leukemia.
AB  - PURPOSE: To conduct a dose-escalation trial of rituximab in patients with chronic
      lymphocytic leukemia (CLL) to define the maximum-tolerated dose (MTD), to
      evaluate first-dose reactions in patients with high circulating lymphocyte
      counts, and to assess the efficacy at higher versus lower doses. PATIENTS AND
      METHODS: Fifty patients with CLL (n = 40) or other mature B-cell lymphoid
      leukemias (n = 10) were treated with four weekly infusions of rituximab. The
      first dose was 375 mg/m(2) for all patients; dose- escalation began with dose 2
      but was held constant for each patient. Escalated doses were from 500 to 2,250
      mg/m(2). RESULTS: Toxicity with the first dose (375 mg/m(2)) was noted in 94% of
      patients but was grade 1 or 2 in most, predominantly fever and chills. Six
      patients (12%) experienced severe toxicity with the first dose, including fever,
      chills, dyspnea, and hypoxia in all six patients, hypotension in five, and
      hypertension in one. Toxicity on subsequent doses was minimal until a dose of
      2,250 mg/m(2) was achieved. Eight (67%) of 12 patients had grade 2 toxicity,
      including fever, chills, nausea, and malaise, although no patient had grade 3 or
      4 toxicity. Severe toxicity with the first dose was significantly more common in
      patients with other B-cell leukemias, occurring in five (50%) of 10 patients
      versus one (2%) of 40 patients with CLL (P <.001). The overall response rate was
      40%; all responses in patients with CLL were partial remissions. Response rates
      were 36% in CLL and 60% in other B-cell lymphoid leukemias. Response was
      correlated with dose: 22% for patients treated at 500 to 825 mg/m(2), 43% for
      those treated at 1,000 to 1,500 mg/m(2), and 75% for those treated at the highest
      dose of 2,250 mg/m(2) (P =.007). The median time to disease progression was 8
      months. Myelosuppression and infections were uncommon. CONCLUSION: Rituximab has
      significant activity in patients with CLL at the higher dose levels. Severe first
      dose reactions were uncommon in patients with CLL, even with high circulating
      lymphocyte counts, but were frequent in patients with other mature B-cell
      leukemias in which CD20 surface expression is increased. Efficacy of rituximab
      was also significant in this group of patients.

PMID- 11304769
TI  - Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma
      in combination with highly active antiretroviral therapy.
AB  - PURPOSE: This study investigated the efficacy, toxicity, and pharmacokinetic
      interactions resulting from simultaneous combination chemotherapy and highly
      active antiretroviral therapy (HAART) for patients with human immunodeficiency
      virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, the effects on
      viral load, CD4 counts, and opportunistic infections were examined with the use
      of combination chemotherapy combined with HAART. PATIENTS AND METHODS: Sixty-five
      patients with previously untreated and measurable disease at any stage of HIV
      associated NHL of intermediate or high grade were entered onto this study at 17
      different centers. The first 40 patients entered onto the study received reduced
      doses of cyclophosphamide and doxorubicin, combined with vincristine and
      prednisone (modified CHOP [mCHOP]), whereas the subsequent 25 patients entered
      onto the study received full doses of CHOP combined with granulocyte colony
      stimulating factor (G-CSF). All patients also received stavudine, lamivudine, and
      indinavir. RESULTS: The complete response rates were 30% and 48% among patients
      who received mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3
      or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of those
      receiving full-dose CHOP combined with G-CSF (25% v 12%). There were similar
      numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%),
      constipation and abdominal pain (18% and 17%), and transaminase elevation (48%
      and 52%) on the modified and full-dose arms of the study, respectively.
      Doxorubicin clearance and indinavir concentration curves were similar among
      patients on this study and historical controls, whereas cyclophosphamide
      clearance was 1.5-fold reduced as compared with control values. Human
      immunodeficiency virus (HIV) load declined from a median baseline value of 29,000
      copies/mL to a median minimum value on therapy of 500 copies/mL. CONCLUSION:
      Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with
      HAART, is effective and tolerable.

PMID- 11304770
TI  - Natural killer/natural killer-like T-cell lymphoma, CD56+, presenting in the
      skin: an increasingly recognized entity with an aggressive course.
AB  - PURPOSE: To describe and identify the clinical and pathologic features of
      prognostic significance for natural killer (NK) and NK-like T-cell (NK/T-cell)
      lymphoma presenting in the skin. PATIENTS AND METHODS: This study was a
      retrospective review of 30 patients with CD56+ lymphomas initially presenting
      with cutaneous lesions, with analysis of clinical and histopathologic parameters.
      RESULTS: The median survival for all patients was 15 months. Those with
      extracutaneous manifestations at presentation (11 patients) had a shorter median
      survival of 7.6 months as compared with those without extracutaneous involvement
      (17 patients), who had a more favorable median survival of 44.9 months (P
      =.0001). Age, gender, extent of cutaneous involvement, and initial response to
      therapy had no statistically significant effect on survival. Seven patients (24%)
      had detectable Epstein-Barr virus (EBV) within neoplastic cells. The patients
      with tumor cells that coexpress CD30 (seven patients) have not yet reached a
      median survival after 35 months of follow-up as compared with those with CD30-
      tumor cells (20 patients), who had a median survival of 9.6 months (P <.02).
      Routine histopathologic characteristics had no prognostic significance nor did
      the presence of CD3epsilon, EBV, or multidrug resistance. CONCLUSION: NK/T-cell
      lymphoma is an aggressive neoplasm; however, a subset with a more favorable
      outcome is identified in this study. The presence of extracutaneous disease at
      presentation is the most important clinical variable and portends a poor
      prognosis. The extent of initial skin involvement does not reliably predict
      outcome. Patients from the United States with NK/T-cell lymphoma presenting in
      the skin have a low incidence of demonstrable EBV in their tumor cells. Patients
      with coexpression of CD30 in CD56 lymphomas tend to have a more favorable
      outcome.

PMID- 11304771
TI  - Results of a pilot study involving the use of an antisense oligodeoxynucleotide
      directed against the insulin-like growth factor type I receptor in malignant
      astrocytomas.
AB  - PURPOSE: Preclinical animal experiments support the use of an antisense
      oligodeoxynucleotide directed against the insulin-like growth factor type I
      receptor (IGF-IR/AS ODN) as an effective potential antitumor agent. We performed
      a human pilot safety and feasibility study using an IGF-IR/AS ODN strategy in
      patients with malignant astrocytoma. PATIENTS AND METHODS: Autologous glioma
      cells collected at surgery were treated ex vivo with an IGF-IR/AS ODN,
      encapsulated in diffusion chambers, reimplanted in the rectus sheath within 24
      hours of craniotomy, and retrieved after a 24-hour in situ incubation. Serial
      posttreatment assessments included clinical examination, laboratory studies, and
      magnetic resonance imaging scans. RESULTS: Other than deep venous thrombosis
      noted in some patients, no other treatment-related side effects were observed.
      IGF-IR/AS ODN-treated cells, when retrieved and assessed, were < or = 2% intact
      by trypan blue exclusion, and none of the intact cells were viable in culture
      thereafter. Parallel Western blots disclosed IGF-IR downregulation to < or = 10%
      after ex vivo antisense treatment. At follow-up, clinical and radiographic
      improvements were observed in eight of 12 patients, including three cases of
      distal recurrence with unexpected spontaneous or postsurgical regression at
      either the primary or the distant intracranial site. CONCLUSION: Ex vivo IGF
      IR/AS ODN treatment of autologous glioma cells induces apoptosis and a host
      response in vivo without unusual side effects. Subsequent transient and sustained
      radiographic and clinical improvements warrant further clinical investigations.

PMID- 11304772
TI  - Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell
      transplantation.
AB  - PURPOSE: To explore the relationship between oral mucositis and selected clinical
      and economic outcomes in blood and marrow transplant patients. PATIENTS AND
      METHODS: Subjects consisted of 92 transplant patients from eight centers who
      participated in a multinational pilot study of a new oral mucositis scoring
      system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients
      were evaluated for erythema and ulceration/pseudomembrane formation beginning on
      the first day of conditioning and continuing for 28 days. We examined the
      relationship between patients' peak OMAS scores and days with fever (body
      temperature > 38.0 degrees C), the occurrence of significant infection, days of
      total parenteral nutrition (TPN), and days of injectable narcotic therapy (all
      over 28 days), days in hospital (over 60 days), total hospital charges for the
      index admission, and vital status at 100 days. RESULTS: Patients' peak OMAS
      scores spanned the full range of possible values (0 to 5) and were significantly
      (P <.05) correlated with all of the outcomes of interest except days with fever
      (P =.21). In analyses controlling for type of graft (autologous v allogeneic) and
      study center, a 1-point increase in peak OMAS score was associated with (1) 1.0
      additional day with fever (P <.01), (2) a 2.1-fold increase in risk of
      significant infection (P <.01), (3) 2.7 additional days of TPN (P <.0001), (4)
      2.6 additional days of injectable narcotic therapy (P <.0001), (5) 2.6 additional
      days in hospital (P <.01), (6) $25,405 in additional hospital charges (P <.0001),
      and (7) a 3.9-fold increase in 100-day mortality risk (P <.01). Mean hospital
      charges were $42,749 higher among patients with evidence of ulceration compared
      with those without (P =.06). CONCLUSION: Oral mucositis is associated with
      significantly worse clinical and economic outcomes in blood and marrow
      transplantation.

PMID- 11304773
TI  - Individualized patient education and coaching to improve pain control among
      cancer outpatients.
AB  - PURPOSE: An estimated 42% of cancer patients suffer from poorly controlled pain,
      in part because of patient-related barriers to pain control. The objective of
      this study was to evaluate the effect of an individualized education and coaching
      intervention on pain outcomes and pain-related knowledge among outpatients with
      cancer-related pain. PATIENTS AND METHODS: English-speaking cancer patients (18
      to 75 years old) with moderate pain over the past 2 weeks were randomly assigned
      to the experimental (n = 34) or control group (n = 33). Experimental patients
      received a 20-minute individualized education and coaching session to increase
      knowledge of pain self-management, to redress personal misconceptions about pain
      treatment, and to rehearse an individually scripted patient-physician dialog
      about pain control. The control group received standardized instruction on
      controlling pain. Data on average pain, functional impairment as a result of
      pain, pain frequency, and pain-related knowledge were collected at enrollment and
      2-week follow-up. RESULTS: At baseline, there were no significant differences
      between experimental and control groups in terms of average pain, functional
      impairment as a result of pain, pain frequency, or pain-related knowledge. At
      follow-up, average pain severity improved significantly more among experimental
      group patients than among control patients (P =.014). The intervention had no
      statistically significant impact on functional impairment as a result of pain,
      pain frequency, or pain-related knowledge. CONCLUSION: Compared with provision of
      standard educational materials and counseling, a brief individualized education
      and coaching intervention for outpatients with cancer-related pain was associated
      with improvement in average pain levels. Larger studies are needed to validate
      these effects and elucidate their mechanisms.

PMID- 11304774
TI  - Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF)
      compared with standard CEF in metastatic breast cancer patients: results of a
      multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord
      Ouest-Mammella Inter Gruppo Group.
AB  - PURPOSE: To evaluate whether an accelerated-intensified cyclophosphamide,
      epirubicin, and fluorouracil (CEF) chemotherapy regimen with the support of
      granulocyte colony-stimulating factor (G-CSF) induces a higher activity and
      efficacy compared with standard CEF in metastatic breast cancer patients.
      PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive
      as first-line chemotherapy either standard CEF (cyclophosphamide 600 mg/m(2),
      epirubicin 60 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 21 days
      (CEF21) or accelerated-intensified CEF (cyclophosphamide 1,000 mg/m(2),
      epirubicin 80 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 14 days
      (HD-CEF14) with the support of G-CSF. Treatment was administered for eight
      cycles. RESULTS: A total of 151 patients were randomized (74 patients on the
      CEF21 arm and 77 on the HD-CEF14 arm). In both arms, the median number of
      administered cycles was eight. The dose-intensity actually administered was 93%
      and 86% of that planned, in CEF21- and HD-CEF14-treated patients, respectively.
      Compared with the CEF21 arm, the dose-intensity increase in the HD-CEF14 arm was
      80%. Both nonhematologic and hematologic toxicities were higher in the HD-CEF14
      arm than in the CEF21 arm. During chemotherapy, four deaths occurred in the HD
      CEF14 arm. No difference in overall response rate (complete plus partial
      responses) was observed: 49% and 51% in the CEF21 and HD-CEF14 arms, respectively
      (P =.94). A slightly non-statistically significant higher percentage of complete
      response was observed in the HD-CEF14 arm (20% v 15%). No difference in efficacy
      was observed. The median time to progression was 14.3 and 12.8 months in the
      CEF21 and HD-CEF14 arms, respectively (P =.69). Median overall survival was 32.7
      and 27.2 months in the CEF21 and HD-CEF14 arms, respectively (P =.16).
      CONCLUSION: In metastatic breast cancer patients, an 80% increase in dose
      intensity of the CEF regimen, obtained by both acceleration and dose
      intensification, does not improve the activity and the efficacy compared with a
      standard dose-intensity CEF regimen.

PMID- 11304775
TI  - Clinical and pharmacologic study of the epirubicin and paclitaxel combination in
      women with metastatic breast cancer.
AB  - PURPOSE: A pharmacokinetic interaction may cause increased cardiotoxicity of
      paclitaxel (PTX) and high cumulative dose of doxorubicin. We tested antitumor
      activity, tolerability, and pharmacokinetics of the lesser cardiotoxic epirubicin
      (EPI) and PTX (ET combination). PATIENTS AND METHODS: Twenty-seven women with
      untreated metastatic breast cancer, median age of 56 years, and prominent
      visceral involvement (74%) were studied. Three-weekly EPI (90 mg/m(2)) and PTX
      (200 mg/m(2) over 3 hours) were given for a maximum nine cycles. EPI was
      administered 24 hours before PTX (E --> T) in cycle 1, and 15 minutes before PTX
      (ET) thereafter. EPI, epirubicinol (EOL), EPI-glucuronide (EPI-glu), EOL
      glucuronide (EOL-glu), PTX, and 6alpha-OH-PTX were measured in plasma and urine
      in 14 women. RESULTS: Patients received 205 cycles of ET and a median EPI dose of
      720 mg/m(2). Grade 4 neutropenia (49% of cycles) was the most frequent toxicity.
      Cardiac contractility was decreased in five patients. Mild congestive heart
      failure occurred in two (7.4%). Response rate was 76% (28% complete). Median
      overall survival was 29 months. On the basis of intrapatient comparison in the
      first 24 hours of E --> T and ET cycles, PTX did not affect EPI disposition, but
      significantly increased plasma exposure to EOL (by 137%), EPI-glu (threefold) and
      EOL-glu (twofold). Urinary excretion of EPI dose went from 8.2% in E --> T to
      11.8% in ET cycles. Clearance of PTX was 30% slower in ET than E --> T. ET cycles
      caused lower neutrophil nadir than E --> T (644 +/- 327 v 195 +/- 91, P <.05)
      CONCLUSION: ET is feasible, devoid of excessive cardiac toxicity, and active. A
      reciprocal pharmacokinetic interference between the two drugs has pharmacodynamic
      consequences, and suggests a direct effect of PTX on EPI metabolism requiring ad
      hoc investigation.

PMID- 11304776
TI  - Dose-dense sequential chemotherapy with epirubicin and paclitaxel versus the
      combination, as first-line chemotherapy, in advanced breast cancer: a randomized
      study conducted by the Hellenic Cooperative Oncology Group.
AB  - PURPOSE: To compare the efficacy of two different schedules of epirubicin and
      paclitaxel, as first-line chemotherapy, in patients with advanced breast cancer
      (ABC). PATIENTS AND METHODS: From October 1997 until May 1999, 183 eligible
      patients with ABC entered the study. Chemotherapy in group A (93 patients)
      consisted of four cycles of epirubicin at a dose of 110 mg/m(2) followed by four
      cycles of paclitaxel at a dose of 225 mg/m(2) in a 3-hour infusion. All cycles
      were repeated every 2 weeks with granulocyte colony-stimulating factor support.
      The therapeutic regimen in group B (90 patients) consisted of epirubicin (80
      mg/m(2)) immediately followed by paclitaxel (175 mg/m(2) in a 3-hour infusion)
      every 3 weeks for six cycles. RESULTS: In total, 79 patients (85%) in group A and
      72 patients (80%) in group B completed treatment. The median relative dose
      intensity of epirubicin was 0.96 in both groups, and that of paclitaxel was 0.96
      and 0.97 in groups A and B, respectively. The complete response rate was higher
      in group A (21.5% v 9% P =.02). Nevertheless, there was no significant difference
      in the overall response rate between the two groups (55% v 42%, P =.10). Severe
      neutropenia was more frequently observed with concurrent treatment. After a
      median follow-up of 16.5 months, median time to progression was 10 months in
      group A and 8.5 months in group B (P =.27), and median survival was 21.5 and 20
      months, respectively (P =.17). CONCLUSION: The present study failed to
      demonstrate a significant difference in overall response rate between dose-dense
      sequential administration of epirubicin and paclitaxel compared with the
      combination of the two drugs given on the same day, even though the sequential
      treatment resulted in a significantly higher complete response rate.

PMID- 11304777
TI  - Impact of systemic treatment on local control for patients with lymph node
      negative breast cancer treated with breast-conservation therapy.
AB  - PURPOSE: To determine the impact of tamoxifen and chemotherapy on local control
      for breast cancer patients treated with breast-conservation therapy. PATIENTS AND
      METHODS: The data from 484 breast cancer patients who were treated with breast
      conserving surgery and radiation were analyzed. Only patients with lymph node
      negative disease were studied to provide comparative groups with a similar stage
      of disease and a similar competing risk for distant metastases. Actuarial local
      control rates of the 277 patients treated with systemic therapy (128,
      chemotherapy with or without tamoxifen; 149, tamoxifen alone) were compared with
      the rates for the 207 patients who received no systemic treatment. Only 10% of
      the patients had positive (2%), close (3%), or unknown margin status (5%).
      RESULTS: Patients treated with systemic therapy had improved 5-year (97.5% v
      89.8%) and 8-year (95.6% v 85.2%) local control rates compared with those that
      did not receive systemic treatment (P =.004, log-rank test). There was no
      statistical difference in local control between patients treated with
      chemotherapy and patients treated with tamoxifen alone (P =.219). Systemic
      treatment, margin status, young patient age, estrogen and progesterone receptor
      status, and primary tumor size were analyzed in a Cox regression analysis. The
      use of systemic treatment was the most powerful predictor of local control:
      patients who did not receive systemic treatment had a relative risk of local
      recurrence of 3.3 (95% confidence interval, 1.5 to 7.5; P =.004). CONCLUSION: In
      this retrospective analysis, systemic therapy appears to contribute to long-term
      local control in patients with lymph node-negative breast cancer treated with
      breast-conservation therapy.

PMID- 11304778
TI  - Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast
      cancer risk evaluation clinic.
AB  - PURPOSE: Data from the Breast Cancer Linkage Consortium suggest that the
      proportion of familial breast and ovarian cancers linked to BRCA1 or BRCA2 may be
      as high as 98% depending on the characteristics of the families, suggesting that
      mutations in BRCA1 or BRCA2 may entirely account for hereditary breast and
      ovarian cancer families. We sought to determine what proportion of families with
      both breast and ovarian cancers seen in a breast cancer risk evaluation clinic
      are accounted for by coding region germline mutations in BRCA1 and BRCA2 as
      compared to a linkage study group. We also evaluated what clinical parameters
      were predictive of mutation status. PATIENTS AND METHODS: Affected women from 100
      families with at least one case of breast cancer and at least one case of ovarian
      cancer in the same lineage were screened for germline mutations in the entire
      coding regions of BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis,
      a polymerase chain reaction-based heteroduplex analysis, or direct sequencing.
      RESULTS: Unequivocal deleterious mutations were found in 55% (55 of 100) of the
      families studied. Mutations in BRCA1 and BRCA2 accounted for 80% and 20% of the
      mutations overall, respectively. Using multivariate analysis, the strongest
      predictors of detecting a mutation in BRCA1 or BRCA2 in this study group were the
      presence of a single family member with both breast and ovarian cancer (P <.0009;
      odds ratio [OR], 5.68; 95% confidence interval [CI], 2.04 to 15.76) and a young
      average age at breast cancer diagnosis in the family (P <.0016; OR, 1.69; 95% CI,
      1.23 to 2.38). CONCLUSION: These results suggest that at least half of
      breast/ovarian families evaluated in a high-risk cancer evaluation clinic may
      have germline mutations in BRCA1 or BRCA2. Whether the remaining families have
      mutations in noncoding regions in BRCA1, mutations in other, as-yet-unidentified,
      low-penetrance susceptibility genes, or represent chance clustering remains to be
      determined.

PMID- 11304779
TI  - Factors predicting the use of breast-conserving therapy in stage I and II breast
      carcinoma.
AB  - PURPOSE: To define patterns of care for the local therapy of stage I and II
      breast cancer and to identify factors used to select patients for breast
      conserving therapy (BCT). PATIENTS AND METHODS: A convenience sample of 16,643
      patients with stage I and II breast cancer treated in 1994 was obtained from
      hospital-based tumor registries. Histologic variables were determined from
      original pathology reports. RESULTS: BCT was performed in 42.6% of patients.
      Multivariate analysis demonstrated that living in the Northeast United States
      (odds ratio [OR], 2.48; 95% confidence interval [CI], 2.16 to 2.84), having a
      clinical T1 tumor (OR, 2.51; 95% CI, 2.27 to 2.78), and having a tumor without an
      extensive intraductal component (OR, 2.07; 95% CI, 1.81 to 2.37) were the
      strongest predictors of breast-conserving surgery. Radiation therapy was given to
      86% of patients who had breast-conserving surgery. Age less than 70 years was the
      most significant predictor of receiving radiation (OR, 2.11; 95% CI, 1.77 to
      2.25). Tumor variables did not correlate with the use of radiation, but favorable
      tumor characteristics were associated with the use of breast-conserving surgery.
      CONCLUSION: Despite strong evidence supporting the use of BCT, the majority of
      women continue to be treated with mastectomy. Predictors of the use of BCT do not
      correspond to those suggested in guidelines.

PMID- 11304780
TI  - Risk factors for recurrence and metastasis after breast-conserving therapy for
      ductal carcinoma-in-situ: analysis of European Organization for Research and
      Treatment of Cancer Trial 10853.
AB  - PURPOSE: In view of the increasing number of patients treated with breast
      conserving treatment (BCT) for ductal carcinoma-in-situ (DCIS), risk factors for
      recurrence and metastasis should be identified. PATIENTS AND METHODS: Clinical
      and pathologic characteristics from patients with DCIS in the European
      Organization for Research and Treatment of Cancer trial 10853 (excision with or
      without radiotherapy) were related to the risk of recurrence. Pathologic features
      were derived from a central review of 863 of the 1,010 randomized cases (85%).
      The median follow-up was 5.4 years. RESULTS: Factors associated with an increased
      risk of local recurrence in the multivariate analysis were young age (< or = 40
      years) (hazard ratio, 2.14; P =.02), symptomatic detection of DCIS (hazard ratio,
      1.80; P =.008), growth pattern (solid and cribriform) (hazard ratios, 2.67 and
      2.69, respectively; P =.012), involved margins (hazard ratio, 2.07; P =.0008),
      and treatment by local excision alone (hazard ratio, 1.74; P =.009). The risk of
      invasive recurrence was not related to the histologic type of DCIS (P =.63), but
      the risk of distant metastasis was significantly higher in poorly differentiated
      DCIS compared with well-differentiated DCIS (hazard ratio, 6.57; P =.01).
      CONCLUSION: Patients with poorly differentiated DCIS have a high risk of distant
      metastasis after invasive local recurrence. Margin status is the most important
      factor in the success of BCT for DCIS; additionally, young age and symptomatic
      detection of DCIS have negative prognostic value.

PMID- 11304781
TI  - Analysis of p53/BAX/p16(ink4a/CDKN2) in esophageal squamous cell carcinoma: high
      BAX and p16(ink4a/CDKN2) identifies patients with good prognosis.
AB  - PURPOSE: We have previously shown that loss of BAX expression is a negative
      prognostic factor in metastatic colorectal cancer. In the present study, we
      addressed the prognostic relevance of BAX and its upstream regulator p53 in
      squamous cell carcinoma (SCC) of the esophagus. Analysis of p16(ink4a/CDKN2) was
      included because p16(ink4a/CDKN2) and p53 were shown previously to cooperate
      during induction of cell cycle arrest and apoptosis. PATIENTS AND METHODS:
      Retrospective analysis of 53 patients with curative intended R0 resection of
      esophageal SCC was done. Protein expression of BAX, p53, and p16(ink4a/CDKN2) was
      investigated by immunohistochemistry. In addition, tumor DNA was screened for BAX
      frameshift mutations by fragment length analysis and for p53 mutations by single
      strand conformation polymorphism-polymerase chain reaction. RESULTS: Overall
      median survival was 13.7 months. Patients with high BAX protein expression had a
      median survival of 19.5 months versus 8.0 months with low BAX expression (P
      <.005). High p16(ink4a/CDKN2) protein expression was associated with a median
      survival of 23.8 months versus 9.7 months with low p16(ink4a/CDKN2) (P =.011).
      The best survival (median, 45.8 months) was seen in a subgroup of 12 patients
      whose tumors bore the combination of both favorite phenotypes (ie, high BAX and
      high p16(ink4a/CDKN2) protein expression). CONCLUSION: In this retrospective
      investigation, the combined analysis of BAX and p16(ink4a/CDKN2) shows subgroups
      in SCC of the esophagus with favorable (p16(ink4a/CDKN2)/BAX high expressing) or
      poor prognosis (loss of p16(ink4a/CDKN2)/loss of BAX). We suggest that such a
      multimarker analysis of apoptosis pathways could be useful for individualization
      of therapeutic strategies in the future, and suggest prospective studies to
      confirm these results.

PMID- 11304782
TI  - Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin
      as first-line treatment in 605 patients with metastatic colorectal cancer:
      results of a randomized phase III study.
AB  - PURPOSE: To compare the response rate, efficacy parameters, and toxicity profile
      of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5
      FU/LV) as first-line treatment in patients with metastatic colorectal cancer.
      PATIENTS AND METHODS: We prospectively randomized 605 patients to treatment with
      oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection
      daily for 5 days in 4-week cycles. RESULTS: The overall objective tumor response
      rate among all randomized patients was significantly higher in the capecitabine
      group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and
      5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log
      rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19),
      and median overall survival times were 12.5 and 13.3 months (P =.974),
      respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a
      significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and
      alopecia. Patients treated with capecitabine also displayed lower incidences of
      grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to
      significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P
      <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more
      frequently associated with capecitabine than with 5-FU/LV treatment. CONCLUSION:
      Oral capecitabine was more active than 5-FU/LV in the induction of objective
      tumor responses. Time to disease progression and survival were at least
      equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also
      demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of
      tolerability.

PMID- 11304783
TI  - Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity
      among patients intolerant to mercaptopurine or azathioprine.
AB  - PURPOSE: To assess thiopurine S-methyltransferase (TPMT) phenotype and genotype
      in patients who were intolerant to treatment with mercaptopurine (MP) or
      azathioprine (AZA), and to evaluate their clinical management. PATIENTS AND
      METHODS: TPMT phenotype and thiopurine metabolism were assessed in all patients
      referred between 1994 and 1999 for evaluation of excessive toxicity while
      receiving MP or AZA. TPMT activity was measured by radiochemical analysis, TPMT
      genotype was determined by mutation-specific polymerase chain reaction
      restriction fragment length polymorphism analyses for the TPMT*2, *3A, *3B, and
      *3C alleles, and thiopurine metabolites were measured by high-performance liquid
      chromatography. RESULTS: Of 23 patients evaluated, six had TPMT deficiency
      (activity < 5 U/mL of packed RBCs [pRBCs]; homozygous mutant), nine had
      intermediate TPMT activity (5 to 13 U/mL of pRBCs; heterozygotes), and eight had
      high TPMT activity (> 13.5 U/mL of pRBCs; homozygous wildtype). The 65.2%
      frequency of TPMT-deficient and heterozygous individuals among these toxic
      patients is significantly greater than the expected 10% frequency in the general
      population (P <.001, chi(2)). TPMT phenotype and genotype were concordant in all
      TPMT-deficient and all homozygous-wildtype patients, whereas five patients with
      heterozygous phenotypes did not have a TPMT mutation detected. Before thiopurine
      dosage adjustments, TPMT-deficient patients experienced more frequent
      hospitalization, more platelet transfusions, and more missed doses of
      chemotherapy. Hematologic toxicity occurred in more than 90% of patients, whereas
      hepatotoxicity occurred in six patients (26%). Both patients who presented with
      only hepatic toxicity had a homozygous-wildtype TPMT phenotype. After adjustment
      of thiopurine dosages, the TPMT-deficient and heterozygous patients tolerated
      therapy without acute toxicity. CONCLUSION: There is a significant (> six-fold)
      overrepresentation of TPMT deficiency or heterozygosity among patients developing
      dose-limiting hematopoietic toxicity from therapy containing thiopurines.
      However, with appropriate dosage adjustments, TPMT-deficient and heterozygous
      patients can be treated with thiopurines, without acute dose-limiting toxicity.

PMID- 11304784
TI  - Patterns of intellectual development among survivors of pediatric
      medulloblastoma: a longitudinal analysis.
AB  - PURPOSE: To examine two competing hypotheses relating to intellectual loss among
      children treated for medulloblastoma (MB): Children with MB either: (1) lose
      previously learned skills and information; or (2) acquire new skills and
      information but at a rate slower than expected compared with healthy same-age
      peers. PATIENTS AND METHODS: Forty-four pediatric MB patients were evaluated who
      were treated with postoperative radiation therapy (XRT) with or without
      chemotherapy. After completion of XRT, a total of 150 examinations were conducted
      by use of the child version of the Wechsler Intelligence SCALES: These
      evaluations provided a measure of intellectual functioning called the estimated
      full-scale intelligence quotient (FSIQ). Changes in patient performance corrected
      for age (scaled scores) as well as the uncorrected performance (raw scores) were
      analyzed. RESULTS: At the time of the most recent examination, the obtained mean
      estimated FSIQ of 83.57 was more than one SD below expected population norms. A
      significant decline in cognitive performance during the time since XRT was
      demonstrated, with a mean loss of 2.55 estimated FSIQ points per year (P =.0001).
      An analysis for the basis of the intelligence quotient (IQ) loss revealed that
      subtest raw score values increased significantly over time since XRT, but the
      rate of increase was less than normally expected, which resulted in decreased IQ
      scores. CONCLUSION: These results support the hypothesis that MB patients
      demonstrate a decline in IQ values because of an inability to acquire new skills
      and information at a rate comparable to their healthy same-age peers, as opposed
      to a loss of previously acquired information and skills.

PMID- 11304785
TI  - Phase I clinical and pharmacokinetic study of rebeccamycin analog NSC 655649
      given daily for five consecutive days.
AB  - PURPOSE: Rebeccamycin analog (NSC 655649) is active against a variety of both
      solid and nonsolid tumor cell lines. We performed a phase I trial to determine
      the maximum-tolerated dose (MTD) of rebeccamycin analog when given on a daily x 5
      schedule repeated every 3 weeks, characterize the toxicity profile using this
      schedule, observe patients for antitumor response, and determine the
      pharmacokinetics of the agent and pharmacodynamic interactions. PATIENTS AND
      METHODS: Thirty assessable patients received a total of 153 cycles according to
      the following dose escalation schema: 60, 80, 106, 141, and 188 mg/m(2)/d x 5
      days. RESULTS: Grade 2 phlebitis occurred in all patients before the use of
      central venous access, placed at dose level 4 and higher. Dose-limiting toxicity
      (DLT), grade 4 neutropenia, occurred at 188 mg/m(2)/d x 5 days in both previously
      treated and chemotherapy-naive patients. Pharmacokinetic analysis revealed a
      three-compartmental model of drug elimination and a long terminal half-life (154
      +/- 55 hours). The percentage drop in absolute neutrophil count correlates with
      the area under the curve infinity. The presence of a second peak during the
      elimination phase as well as a high concentration of NSC 655649 in biliary fluid
      compared with the corresponding plasma measurement (one patient) is suggestive of
      enterohepatic circulation. Two partial responses, two minor responses, and six
      prolonged (> 6 months) cases of stable disease were observed. Of these, three
      patients with gallbladder cancer and one patient with cholangiocarcinoma
      experienced either a minor response or a significant period of freedom from
      progression. CONCLUSION: The recommended phase II dose for NSC 665649 on a daily
      x 5 every 3 weeks schedule is 141 and 165 mg/m(2)/d for patients with prior and
      no prior therapy, respectively, with DLT being neutropenia. During this phase I
      trial, encouraging antitumor activity was been observed.

PMID- 11304786
TI  - Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory
      neoplasms.
AB  - PURPOSE: To define the maximum tolerated dose (MTD) and dose-limiting toxicity
      (DLT) of the novel protein kinase inhibitor, UCN-01 (7-hydroxystaurosporine),
      administered as a 72-hour continuous intravenous infusion (CIV). PATIENTS AND
      METHODS: Forty-seven patients with refractory neoplasms received UCN-01 during
      this phase I trial. Total, free plasma, and salivary concentrations were
      determined; the latter were used to address the influence of plasma protein
      binding on peripheral tissue distribution. The phosphorylation state of the
      protein kinase C (PKC) substrate alpha-adducin and the abrogation of DNA damage
      checkpoint also were assessed. RESULTS: The recommended phase II dose of UCN-01
      as a 72-hour CIV is 42.5 mg/m(2)/d for 3 days. Avid plasma protein binding of UCN
      01, as measured during the trial, dictated a change in dose escalation and
      administration schedules. Therefore, nine patients received drug on the initial 2
      week schedule, and 38 received drug on the recommended 4-week schedule. DLTs at
      53 mg/m(2)/d for 3 days included hyperglycemia with resultant metabolic acidosis,
      pulmonary dysfunction, nausea, vomiting, and hypotension. Pharmacokinetic
      determinations at the recommended dose of 42.5 mg/m(2)/d for 3 days included mean
      total plasma concentration of 36.4 microM (terminal elimination half-life range,
      447 to 1176 hours), steady-state volume of distribution of 9.3 to 14.2 L, and
      clearances of 0.005 to 0.033 L/h. The mean total salivary concentration was 111
      nmol/L of UCN-01. One partial response was observed in a patient with melanoma,
      and one protracted period ( > 2.5 years) of disease stability was observed in a
      patient with alk-positive anaplastic large-cell lymphoma. Preliminary evidence
      suggests UCN-01 modulation of both PKC substrate phosphorylation and the DNA
      damage-related G(2) checkpoint. CONCLUSION: UCN-01 can be administered safely as
      an initial 72-hour CIV with subsequent monthly doses administered as 36-hour
      infusions.

PMID- 11304787
TI  - When is a tumor marker ready for prime time? A case study of c-erbB-2 as a
      predictive factor in breast cancer.
AB  - PURPOSE: c-erbB-2 (HER-2, c-neu) might play a role as a predictive factor in
      breast cancer. However, the clinical utility of the marker in this disease is
      still not established. We conducted a critical analysis of the literature, in
      which we reviewed the factors that contribute to the lack of acceptance of c-erbB
      2 for clinical use and attempted to determine the predictive role of c-erbB-2 for
      response to specific therapies. METHODS: We conducted a MEDLINE literature search
      using the keywords c-erbB-2, HER2, neu, and breast cancer, reviewed the
      references included in each publication, and reviewed abstracts that have been
      reported in the 1997-2000 proceedings to the American Association of Cancer
      Research and American Society for Clinical Oncology annual meetings. RESULTS: The
      preclinical and clinical data reported to date suggest that amplification or
      overexpression of c-erbB-2 is a weak to moderate negative pure prognostic factor.
      c-erbB-2 seems to be a weak to moderate negative predictive factor for response
      to endocrine therapy. The marker is also a moderate negative predictive factor
      for response to alkylating agents and a moderate positive predictive factor for
      response to anthracyclines. The data regarding response to taxanes or
      radiotherapy are not sufficient to make recommendations regarding treatment
      decision making. Finally, c-erbB-2 is a strong predictive factor for response to
      trastuzumab. CONCLUSION: We conclude that, in the adjuvant setting, c-erbB-2
      status should not be used to determine whether a woman should receive adjuvant
      systemic therapy (weak prognostic factor). In addition, c-erbB-2 status should
      not be used to determine whether a patient should receive endocrine therapy. When
      adjuvant chemotherapy is recommended, anthracycline-based therapy should be the
      preferred regimen for c-erbB-2-positive patients. However, when anthracyclines
      are contraindicated, alkylating agent-based therapy should not be withheld. To
      determine the true predictive role and strength of the marker for response to
      each therapy, prospective randomized clinical trials or formal meta-analyses are
      required.

PMID- 11304788
TI  - Hormone replacement therapy after breast cancer: a systematic review and
      quantitative assessment of risk.
AB  - PURPOSE: Hormone replacement therapy (HRT) is typically withheld from women with
      breast cancer because of concern that it might increase the risk of recurrence.
      The purpose of this study was to quantify the risk of recurrent breast cancer
      associated with HRT among breast cancer survivors. METHODS: We performed a
      systematic literature review through May 1999, calculating the relative risk (RR)
      of breast cancer recurrence in each study by comparing the number of recurrences
      in the HRT group to those in the control group. In studies that did not contain a
      control group, we constructed one by estimating the expected number of
      recurrences based on data from the Early Breast Cancer Trialists' Collaborative
      Group, adjusting for nodal status and disease-free interval. RRs across all
      studies were combined using random-effects models. RESULTS: Of the 11 eligible
      studies, four had control groups and included 214 breast cancer survivors who
      began HRT after a mean disease-free interval of 52 months. Over a mean follow-up
      of 30 months, 17 of 214 HRT users experienced recurrence (4.2% per year),
      compared with 66 of 623 controls (5.4% per year). HRT did not seem to affect
      breast cancer recurrence risk (RR = 0.64, 95% confidence interval [CI], 0.36 to
      1.15). Including all 11 studies in the analyses (669 HRT users), using estimated
      control groups for the seven uncontrolled trials, the combined RR was 0.82 (95%
      CI, 0.58 to 1.15). CONCLUSION: Although our analyses suggest that HRT has no
      significant effect on breast cancer recurrence, these findings were based on
      observational data subject to a variety of biases.

PMID- 11304789
TI  - Nodal metastasis is highly consistent in squamous cell carcinoma of the vulva.

PMID- 11304790
TI  - Surgery in advanced epithelial ovarian cancer.

PMID- 11304791
TI  - Intangible risks of complementary and alternative medicine.

PMID- 11304793
TI  - The emergence of electron tomography as an important tool for investigating
      cellular ultrastructure.
AB  - Electron tomography has emerged as the leading method for the study of three
      dimensional (3D) ultrastructure in the 5-20-nm resolution range. It is ideally
      suited for studying cell organelles, subcellular assemblies and, in some cases,
      whole cells. Tomography occupies a place in 3D biological electron microscopy
      between the work now being done at near-atomic resolution on isolated
      macromolecules or 2D protein arrays and traditional serial-section
      reconstructions of whole cells and tissue specimens. Tomography complements
      serial-section reconstruction by providing higher resolution in the depth
      dimension, whereas serial-section reconstruction is better able to trace
      continuity over long distances throughout the depth of a cell. The two techniques
      can be combined with good results for favorable specimens. Tomography also
      complements 3D macromolecular studies by offering sufficient resolution to locate
      the macromolecular complexes in their cellular context. The technology has
      matured to the point at which application of electron tomography to specimens in
      plastic sections is routine, and new developments to overcome limitations due to
      beam exposure and specimen geometry promise to further improve its capabilities.
      In this review we give a brief description of the methodology and a summary of
      the new insights gained in a few representative applications.(J Histochem
      Cytochem 49:553-563, 2001)

PMID- 11304794
TI  - Oxygen insensitivity of the histochemical assay of glucose-6-phosphate
      dehydrogenase activity for the detection of (pre)neoplasm in rat liver.
AB  - Oxygen insensitivity of the histochemical assay to detect glucose-6-phosphate
      dehydrogenase (G6PD) activity with NT as tetrazolium salt has been proved to be a
      powerful tool to discriminate various types of adenocarcinoma from normal
      tissues. Here we investigated whether this phenomenon can also be applied to
      differentiate between chemically induced hepatocellular (pre)neoplasms and normal
      liver tissue in rats. Residual activity (percentage of the amount of final
      reaction product that is generated in oxygen and that is generated in nitrogen)
      was 60% in (pre)neoplastic cells and 6% in normal liver parenchymal cells. This
      means that the oxygen insensitivity test is a useful tool to distinguish
      (pre)neoplasms from normal rat liver tissue. N-Ethylmaleimide, a blocker of SH
      groups, did not affect G6PD activity in (pre)neoplastic cells, whereas activity
      in normal cells was reduced by half. Therefore, the absence of essential SH
      groups in G6PD in (pre)neoplastic cells is held responsible for the oxygen
      insensitivity phenomenon. We conclude that oxygen insensitivity of the
      histochemical assay for G6PD activity is a fast, easy, and cheap tool to diagnose
      (pre)neoplasms in rat liver. Discrimination is likely to be based on altered
      properties of the enzyme in (pre)neoplastic cells. (J Histochem Cytochem 49:565
      571, 2001)

PMID- 11304795
TI  - Different regulation of connexin26 and ZO-1 in cochleas of developing rats and of
      guinea pigs with endolymphatic hydrops.
AB  - Using confocal microscopy and morphometry, we analyzed the expression of
      connexin26 (Cx26) and ZO-1 in rat cochlea during the postnatal period to
      elucidate spatiotemporal changes in gap junctions and tight junctions during
      auditory development. We also studied changes in these junctions in experimental
      endolymphatic hydrops in the guinea pig. In the adult rat cochlear lateral wall,
      Cx26 was detected in fibrocytes in the spiral ligament and in the basal cell
      layer of the stria vascularis, whereas ZO-1 was detected in the apical surfaces
      of marginal cells and in the basal cell layer. During postnatal development, Cx26
      expression increased mainly in the spiral ligament, whereas ZO-1 expression
      increased in the basal cell layer. The morphometry of Cx26 showed a sigmoid time
      course with a rapid increase on postnatal day (PND) 14, whereas that of ZO-1
      showed a marked increase on PND 7. In experimental endolymphatic hydrops, the
      expression of Cx26 significantly decreased, whereas there were no obvious changes
      in the expression of ZO-1. These results indicate that gap junctions and tight
      junctions in the cochlea increase in a different spatiotemporal manner during the
      development of auditory function and that gap junctions and tight junctions in
      the cochlea are differentially regulated in experimental endolymphatic hydrops.
      (J Histochem Cytochem 49:573-586, 2001)

PMID- 11304796
TI  - Immunohistochemical demonstration of alpha1,4-N-acetylglucosaminyltransferase
      that forms GlcNAcalpha1,4Galbeta residues in human gastrointestinal mucosa.
AB  - alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT) is a glycosyltransferase
      that mediates transfer of GlcNAc to betaGal residues with alpha1,4-linkage,
      forming GlcNAcalpha1--> 4Galbeta-->R structures. In normal human tissues,
      glycoproteins having GlcNAcalpha1-->4Galbeta-->R structures at non-reducing
      terminals are exclusively limited to the mucins secreted from glandular mucous
      cells of gastric mucosa, Brunner's gland of duodenum, and accessory gland of
      pancreaticobiliary tract. Recently, we have isolated a cDNA encoding human
      alpha4GnT by expression cloning. Although alpha4GnT plays a key role in producing
      this unique glycan in vitro, the actual localization of alpha4GnT was not
      determined. In this study we examined the localization of alpha4GnT in various
      human tissues, including gastrointestinal mucosa, using a newly developed
      antibody against human alpha4GnT. The specificity of the antibody was confirmed
      by analyses of human gastric adenocarcinoma AGS cells transfected by alpha4GnT
      cDNA. Expression of alpha4GnT was largely associated with the Golgi region of
      mucous cells that produce the mucous glycoproteins having GlcNAcalpha1-->4Galbeta
      ->R, such as the glandular mucous cells of stomach and Brunner's gland. An
      immunoprecipitation experiment disclosed that two distinct mucin proteins, MUC5AC
      and MUC6 present in gastric mucin, carried the GlcNAcalpha1-->4Galbeta-->R
      structures. These results indicate that alpha4GnT is critical to form the mucous
      glycoproteins having GlcNAcalpha1-->4Galbeta-->R on MUC6 and MUC5AC in vivo.(J
      Histochem Cytochem 49:587-596, 2001)

PMID- 11304797
TI  - Immunohistochemical localization of activated EGF receptor in human eccrine and
      apocrine sweat glands.
AB  - Epidermal growth factor (EGF) is secreted into sweat from secretory cells of
      human sweat glands. The function of EGF in sweat is poorly understood. The
      biological function of EGF is exerted by the binding of EGF to the receptor
      (EGFR) and its activation. Therefore, we immunohistochemically localized the
      activated form of EGFR in human eccrine and apocrine sweat glands to assess the
      functional importance of the EGF-EGFR system in human sweat glands. Frozen
      sections of human skin were stained with a monoclonal antibody (MAb) specific for
      tyrosine-phosphorylated (activated) EGFR and with an MAb that stains both
      activated and non-activated EGFR. In the secretory portion of eccrine sweat
      glands, nuclei of the secretory cells were stained with the anti-activated EGFR
      MAb. In coiled and straight portions of eccrine sweat ducts, nuclei of luminal
      and peripheral cells were stained with the antibody specific for activated EGFR.
      Luminal cell membranes and luminal cytoplasm of inner ductal cells possessed non
      activated EGFR. In the secretory portion of apocrine sweat glands, activated
      EGFRs were present in cytoplasm and nuclei of secretory cells. These data suggest
      that EGF, already known to be present in the cytoplasm of secretory cells in
      eccrine and apocrine sweat glands, activates EGFR in the nuclei of secretory
      cells themselves in an intracrine manner. Because ductal cells do not express
      EGF, EGF in the sweat secreted from the secretory cells should activate EGFR in
      the ductal cells in a paracrine manner. (J Histochem Cytochem 49:597-601, 2001)

PMID- 11304798
TI  - Single-copy gene detection using branched DNA (bDNA) in situ hybridization.
AB  - We have developed a branched DNA in situ hybridization (bDNA ISH) method for
      detection of human papillomavirus (HPV) DNA in whole cells. Using human cervical
      cancer cell lines with known copies of HPV DNA, we show that the bDNA ISH method
      is highly sensitive, detecting as few as one or two copies of HPV DNA per cell.
      By modifying sample pretreatment, viral mRNA or DNA sequences can be detected
      using the same set of oligonucleotide probes. In experiments performed on mixed
      populations of cells, the bDNA ISH method is highly specific and can distinguish
      cells with HPV-16 from cells with HPV-18 DNA. Furthermore, we demonstrate that
      the bDNA ISH method provides precise localization, yielding positive signals
      retained within the subcellular compartments in which the target nucleic acid
      sequences are localized. As an effective and convenient means for nucleic acid
      detection, the bDNA ISH method is applicable to the detection of cancers and
      infectious agents. (J Histochem Cytochem 49:603-611, 2001)

PMID- 11304799
TI  - The role of 15-lipoxygenase in disruption of the peroxisomal membrane and in
      programmed degradation of peroxisomes in normal rat liver.
AB  - Our earlier electron microscopic observations revealed that prolonged exposure of
      glutaraldehyde-fixed rat liver sections to buffer solutions induced focal
      membrane disruptions of peroxisomes with catalase diffusion as shown
      cytochemically. Recently, it was suggested that 15-lipoxygenase (15-LOX) might be
      involved in natural degradation of membrane-bound organelles in reticulocytes by
      integrating into and permeabilizing the organelle membranes, leading to the
      release of matrix proteins. We have now investigated the localization of 15-LOX
      and its role in degradation of peroxisomal membranes in rat liver. Aldehyde-fixed
      liver slices were incubated in a medium that conserved the 15-LOX activity,
      consisting of 50 mM HEPES-KOH buffer (pH 7.4), 5 mM mercaptoethanol, 1 mM
      MgCl(2), 15 mM NaN(3), and 0.2 M sucrose, in presence or absence of 0.5-0.05 mM
      propyl gallate or esculetin, two inhibitors of 15-LOX. The exposure of aldehyde
      fixed liver sections to this medium induced focal disruptions of peroxisome
      membranes and catalase diffusion around some but not all peroxisomes. This was
      significantly reduced by both 15-LOX inhibitors, propyl gallate and esculetin,
      with the latter being more effective. Double immunofluorescent staining for 15
      LOX and catalase revealed that 15-LOX was co-localized with catalase in some but
      not all peroxisomes in rat hepatocytes. By postembedding immunoelectron
      microscopy, gold labeling was localized on membranes of some peroxisomes. These
      observations suggest that 15-LOX is involved in degradation of peroxisomal
      membranes and might have a physiological role in programmed degradation and
      turnover of peroxisomes in hepatocytes. (J Histochem Cytochem 49:613-621, 2001)

PMID- 11304800
TI  - A new rapid immunohistochemical staining technique using the EnVision antibody
      complex.
AB  - Rapid immunohistochemical investigation, in addition to staining with hematoxylin
      and eosin, would be useful during intraoperative frozen section diagnosis in some
      cases. This study was undertaken to investigate whether the recently described
      EnVision system, a highly sensitive two-step immunohistochemical technique, could
      be modified for rapid immunostaining of frozen sections. Forty-five primary
      antibodies were tested on frozen sections from various different tissues. After
      fixation in acetone for 1 min and air-drying, the sections were incubated for 3
      min each with the primary antibody, the EnVision complex (a large number of
      secondary antibodies and horseradish peroxidase coupled to a dextran backbone),
      and the chromogen (3,3'diaminobenzidine or 3-amino-9-ethylcarbazole). All
      reactions were carried out at 37C. Specific staining was seen with 38 antibodies
      (including HMB-45 and antibodies against keratin, vimentin, leukocyte common
      antigen, smooth muscle actin, synaptophysin, CD34, CD3, CD20, and prostate
      specific antigen). A modification of the EnVision method allows the detection of
      a broad spectrum of antigens in frozen sections in less than 13 min. This method
      could be a useful new tool in frozen section diagnosis and research. (J Histochem
      Cytochem 49:623-630, 2001)

PMID- 11304801
TI  - Immunocytochemical localization of secretory phospholipase A(2)-like protein in
      the pituitary gland and surrounding tissue of the bullfrog, Rana catesbeiana.
AB  - Previously, we obtained a protein that has considerable amino acid sequence
      homology with secretory phospholipase A(2) (PLA(2)) from a bullfrog pituitary
      fraction obtained during the purification of thyrotropin (TSH). Subsequently,
      partial amino acid sequence (N-terminal 45 amino acid residues) analysis revealed
      this protein to be identical to the N-terminal amino acid sequence of otoconin
      22, the major protein of aragonitic otoconia in the Xenopus saccule. In this
      study we developed an antibody against the N-terminal peptide of the bullfrog
      protein and applied it for immunocytochemical study of the pituitary and its
      surrounding tissue. Western blotting analysis showed that this antibody
      recognizes a 20.4-kD protein that has a molecular mass close to that of otoconin
      22. Immunohistochemical reaction with the antibody was not found in any anterior
      pituitary cells but was intense in the monolayer epithelial cells of the
      endolymphatic sac surrounding the pituitary gland, which is a major storage site
      of calcium carbonate in amphibians. An electron microscopic study revealed that
      the cuboidal cells in the endolymphatic sac contained large, polymorphic
      secretory granules in their apical cytoplasm. Immunogold particles indicating the
      presence of a PLA(2)-like protein were observed predominately in these secretory
      granules. These findings support the view that this PLA(2)-like protein obtained
      during purification of TSH was derived from the endolymphatic sac adhering to the
      pituitary and that this protein is a bullfrog otoconin. (J Histochem Cytochem
      49:631-637, 2001)

PMID- 11304802
TI  - The cortactin-binding postsynaptic density protein proSAP1 in non-neuronal cells.
AB  - Proline-rich synapse-associated protein-1 (ProSAP1) is a neuronal PDZ domain
      containing protein that has recently been identified as an essential element of
      the postsynaptic density. Via its interaction with the actin-binding protein
      cortactin and its integrative function in the organization of neurotransmitter
      receptors, ProSAP1 is believed to be involved in the linkage of the postsynaptic
      signaling machinery to the actin-based cytoskeleton, and may play a role in the
      cytoskeletal rearrangements that underlie synaptic plasticity. As a result of our
      ongoing studies on the distribution and function of this novel PDZ domain
      protein, we now report that the expression of ProSAP1 is restricted neither to
      neurons and interneuronal junctions nor to the nervous system. Using
      immunohistochemical techniques in conjunction with specific antibodies, we found
      that, in the CNS, ProSAP1 can be detected in certain glial cells, such as
      ependymal cells, tanycytes, subpial/radial astrocytes, and in the choroid plexus
      epithelium. Moreover, our immunohistochemical analyses revealed the presence of
      ProSAP1 in endocrine cells of the adenohypophysis and of the pancreas, as well as
      in non-neuronal cell types of other organs. In the pancreas, ProSAP1
      immunoreactivity was also localized in the duct system of the exocrine
      parenchyma. Our findings demonstrate that, in addition to neurons, ProSAP1 is
      present in various non-neuronal cells, in which it may play a crucial role in the
      dynamics of the actin-based cytoskeleton. (J Histochem Cytochem 49:639-648, 2001)

PMID- 11304803
TI  - Changes of AT(2) receptor levels in the rat adrenal cortex and medulla induced by
      bilateral nephrectomy and its modulation by circulating ANG II.
AB  - We studied regulation of the AT(2) receptor by investigating the effect of
      bilateral nephrectomy (bNX) in Sprague-Dawley rats. The expression of aldosterone
      synthase (CYP11B2) and AT(2) receptor mRNA was detected by nonradioactive in situ
      hybridization. AT(2) receptor mRNA was detected in cells of the first two or
      three subcapsular cell layers of the zona glomerulosa (ZG) and in the medulla of
      sham-operated animals. After bNX, the number and area of distribution of AT(2)
      receptor-positive cells increased in the ZG. This was associated with an
      enlargement of the steroidogenic active ZG and with reduced proliferation rate
      (sham 5.9 +/- 0.9%; bNX 2.4 +/- 0.2%; p<0.02). Infusion of angiotensin II (ANG
      II; 200 ng/kg/min SC for 56 hr) to bNX rats did not reverse the effect of
      nephrectomy on the distribution of AT(2) receptor expression, although mRNA
      levels per cell were reduced compared to NX alone. ANG II infusion decreased
      proliferation rate further (0.4 +/- 0.07%; p<0.001). In the adrenal medulla after
      bNX, decreased expression of the AT(2) receptor was associated with increased
      proliferation (2.6 +/- 0.2% vs 6.6 +/- 0.5%). These results demonstrate
      differential regulation of the AT(2) receptor in the adrenal gland and suggest
      that expression of the AT(2) receptor is involved in regulating proliferation and
      differentiation in the ZG and medulla. (J Histochem Cytochem 49:649-656, 2001)

PMID- 11304804
TI  - Secretion of carbonic anhydrase isoenzyme VI (CA VI) from human and rat lingual
      serous von Ebner's glands.
AB  - Salivary carbonic anhydrase VI (CA VI) appears to contribute to taste function by
      protecting taste receptor cells (TRCs) from apoptosis. The serous von Ebner's
      glands locating in the posterior tongue deliver their saliva into the bottom of
      the trenches surrounding the TRC-rich circumvallate and foliate papillae. Because
      these glands deliver their saliva directly into the immediate vicinity of TRCs,
      we investigated whether CA VI is secreted by the von Ebner's glands, using
      immunochemical techniques. The immunohistochemical results showed that CA VI is
      present in the serous acinar cells, ductal cells, and ductal content of von
      Ebner's glands and in the demilune and ductal cells plus ductal content of rat
      lingual mucous glands. More importantly, CA VI was also detected in taste buds
      and in the taste pores. Western blotting of saliva collected from the orifices of
      human von Ebner's glands and CAs purified from rat von Ebner's glands confirmed
      that CA VI is expressed in these glands and secreted to the bottom of the
      trenches surrounding the circumvallate and foliate papillae. These findings are
      consistent with the hypothesis that locally secreted CA VI is implicated in the
      paracrine modulation of taste function and TRC apoptosis. (J Histochem Cytochem
      49:657-662, 2001)

PMID- 11304805
TI  - The use of counterflow centrifugation to enrich gonadotropes and somatotropes.
AB  - Counterflow centrifugation produces populations of gonadotropes or growth hormone
      (GH) cells enriched to 90% in a Beckman elutriator. The pituitary populations are
      first separated by size into three fractions applying different flow rates,
      stimulated with either gonadotropin-releasing hormone (GnRH) to enlarge the
      gonadotropes or growth hormone-releasing hormone (GHRH) to enlarge the
      somatotropes for 3 hr. The fractions are re-eluted, first at the original flow
      rates and then at higher flow rates to separate enlarged gonadotropes or
      somatotropes. Most other cell types are reduced to less than 5%. However, co
      storage of GH and gonadotropin antigens is seen in either population. Enriched
      gonadotropes or somatotropes can be used in studies of proliferation, autocrine
      or paracrine regulation, or ion channel functions.(J Histochem Cytochem 49:663
      664, 2001)

PMID- 11304806
TI  - Differential expression of estradiol receptors alpha and beta by gonadotropes
      during the estrous cycle.
AB  - This study focused on expression of estradiol receptors (ER) during the estrous
      cycle. Labeling for ERalpha or beta antigens and luteinizing hormone (LH) or
      follicle-stimulating hormone (FSH) beta-subunits was done on freshly dispersed
      pituitary cells. The lowest expression of ERalpha and beta was seen in estrus
      (23% and 12%, respectively). Expression increased to 42-54% of pituitary cells by
      diestrus. In males, cells with ERalpha or beta were 37% or 20% of the population,
      respectively. ERalpha or beta and gonadotropin antigens were in 6-9% of pituitary
      cells from male rats. Early in the cycle (estrus and metestrus), less than 5% of
      pituitary cells expressed ERalpha or beta with gonadotropins. These values
      doubled to reach a peak of 10% during proestrus (just before ovulation). These
      data show that a rise in expression of both ERalpha and ERbeta is a part of
      preovulatory differentiation of pituitary gonadotropes.(J Histochem Cytochem
      49:665-666, 2001)

PMID- 11304807
TI  - Defining a molecularly normal colon.
AB  - As techniques evolve that allow molecular characterization of disease processes
      such as cancer, definition of "normal" at a molecular level becomes increasingly
      important. Increasingly large numbers of mutations are found at the genomic
      level, but whether all of those mutations contribute to the malignant state of a
      carcinoma cell is not clear. Without knowledge of what constitutes normality on
      the proteomic level in an organ or cell, we cannot determine what genomic changes
      are physiologically important. Traditionally, colon cancer is identified and
      classified by histological criteria. Margins of the colon are defined as "grossly
      uninvolved" when the histology is indistinguishable from that of normal (free
      from disease) colon. By using molecular pathology techniques and working backward
      from colon adenocarcinoma to hypoplastic polyps to presumably normal mucosa, we
      defined some of those protein differences. Our results may provide a molecular
      basis for identifying tumor formation and progression in situ.(J Histochem
      Cytochem 49:667-668, 2001)

PMID- 11304808
TI  - Identification of genes differentially expressed in benign prostatic hyperplasia.
AB  - Differences between benign prostatic hyperplasia (BPH) and normal prostate tissue
      at the level of mRNA expression provide an opportunity to identify candidate
      genes for this disease. A cDNA subtraction procedure was used to isolate
      differentially expressed genes in BPH. The subtraction was done by solution
      hybridization of BPH cDNA against excess normal prostate cDNA. We identified
      known, EST, and novel genes by sequence and database analysis of the subtracted
      cDNAs. Several of these cDNAs were used as probes in Northern blotting analysis
      to confirm over-expression of their corresponding mRNAs in BPH tissues. One
      highly upregulated sequence of interest shared identity with a known mRNA
      encoding human NELL2, a protein containing epidermal growth factor-like domains.
      NELL2 was not previously reported to be expressed in prostate and may code for a
      novel prostatic growth factor. In situ hybridization analysis of hyperplastic
      prostate specimens demonstrated that NELL2 mRNA expression is predominantly
      localized in basal cells of the epithelium. Disease-related changes in the levels
      of NELL2 may contribute to alterations in epithelial-stromal homeostasis in BPH.
      (J Histochem Cytochem 49:669-670, 2001)

PMID- 11304809
TI  - Quantitative immunohistochemistry of glucose transport protein (Glut3) expression
      in the rat hippocampus during aging.
AB  - Immunohistochemistry of Glut3 (45 kD), an integral membrane peptide mediating the
      transport of glucose in neurons, was carried out in the hippocampus of 3- and 28
      month-old rats to assess the effect of age on energy metabolism. Free-floating
      sections of fixed-frozen hippocampi were processed for quantitative
      immunohistochemistry of Glut3. A rabbit affinity-purified antibody identified
      Glut3 immunoreactivity. Glut3 staining was intense in neuropil, axons, and
      dendrites, whereas nerve cell bodies were unstained. With aging, Glut3 reactivity
      was significantly decreased in the inner molecular layer of the hippocampal
      dentate gyrus (-46%) and the mossy fibers of the CA3 sector (-34%), whereas the
      stratum radiatum of CA1 did not show any difference due to age. These data
      document an age-dependent decrease in Glut3 expression in discrete areas of rat
      hippocampus. Glut3 constitutes the predominant glucose transporter in neurons and
      is found abundantly in regions with high synaptic density characterized by
      frequent bursts of function-adequate metabolic activity. Our findings therefore
      lend further support to the critical role of an impaired metabolism in age
      related brain dysfunctions and disease.(J Histochem Cytochem 49:671-672, 2001)

PMID- 11304810
TI  - Monitoring signal transduction in cancer: tyrosine kinase gene expression
      profiling.
AB  - Abnormal expression of tyrosine kinase (TK) genes is common in tumors, in which
      it is believed to alter cell growth and response to external stimuli such as
      growth factors and hormones. Although the etiology and pathogenesis of carcinomas
      of the thyroid or breast remain unclear, there is evidence that the expression of
      TK genes, such as receptor tyrosine kinases, or mitogen-activated protein
      kinases, is dysregulated in these tumors, and that overexpression of particular
      TK genes due to gene amplification, changes in gene regulation, or structural
      alterations leads to oncogenic transformation of epithelial cells. We developed a
      rapid scheme to measure semiquantitatively the expression levels of 50-100 TK
      genes. Our assay is based on RT-PCR with mixed based primers that anneal to
      conserved regions in the catalytic domain of TK genes to generate gene-specific
      fragments. PCR products are then labeled by random priming and hybridized to DNA
      microarrays carrying known TK gene targets. Inclusion of differently labeled
      fragments from reference or normal cells allows identification of TK genes that
      show altered expression levels during malignant transformation or tumor
      progression. Examples demonstrate how this innovative assay might help to define
      new markers for tumor progression and potential targets for disease intervention.
      (J Histochem Cytochem 49:673-674, 2001)

PMID- 11304811
TI  - The development of the art and science of strabismology outside North America:
      part I.

PMID- 11304812
TI  - A comparison of grating visual acuity, strabismus, and reoperation outcomes among
      children with aphakia and pseudophakia after unilateral cataract surgery during
      the first six months of life.
AB  - PURPOSE: The method of correcting aphakia after unilateral cataract extraction
      during infancy is controversial. Some authorities advocate correction with an
      intraocular lens (IOL) whereas others advocate correction with a contact lens
      (CL). We compared grating visual acuity, alignment, and reoperative outcomes in
      age-matched children treated with these 2 modalities at 5 clinical centers.
      METHODS: Twenty-five infants born in 1997 or 1998 with a dense unilateral
      congenital cataract who had cataract surgery coupled with (IOL group, n = 12) or
      without (CL group, n = 13) primary IOL implantation were enrolled in this study.
      All patients were prescribed half-time occlusion therapy. In July 1999, their
      grating visual acuities, ocular alignments, and reoperation rates were assessed.
      RESULTS: The mean grating visual acuity (LogMAR) for the affected eye was 0.70 +/
      0.32 for the IOL group and 0.87 +/- 0.31 for the CL group (P =.19). The mean
      interocular difference in grating visual acuity was 0.26 +/- 0.30 for the IOL
      group and 0.50 +/- 0.28 for the CL group (P =.048). The incidence of strabismus
      (>10 PD) was 75% in the IOL group compared with 92% in the CL group (P =.24). The
      incidence of reoperations was 83% in the IOL group compared with 23% in the CL
      group (P =.003). CONCLUSIONS: Our preliminary data suggest that correcting
      aphakia after unilateral congenital cataract surgery with primary IOL
      implantation results in an improved visual outcome but a higher rate of
      complications requiring reoperation. A randomized clinical trial, the Infant
      Aphakia Treatment Study, is planned to further study the optimal treatment for
      aphakia following unilateral cataract extraction during infancy.

PMID- 11304813
TI  - The double-bellied inferior oblique muscle: clinical correlates.
AB  - PURPOSE: We previously reported an 8% incidence of double-bellied inferior
      oblique (IO) muscles at the surgical capture site (10-12 mm from insertion) in
      cadaveric specimens. This companion study sought to determine how often this
      anomaly is encountered at surgery for clinically overacting IO muscles and
      whether clinical findings or surgical outcomes in cases with double-bellied
      muscles differ from those with single-bellied muscles. METHODS: For 7 years we
      collected preoperative, intraoperative, and postoperative data on all patients
      for whom one surgeon performed primary IO weakening operations for overactions.
      We compared eyes with double-bellied IO muscles to those with single-bellied
      muscles on 4 variables--gradings of preoperative IO and superior oblique (SO)
      actions, presence of fundus excyclotropia, differences between horizontal
      deviations in upgaze and downgaze, and presence and sizes of primary position
      hypertropias--to determine whether one or more of them could predict the presence
      of a double-bellied muscle. Finally, we assessed postoperative IO actions to
      determine whether the presence of a double-bellied muscle influenced the
      effectiveness of IO weakening surgery in reducing overaction. RESULTS: Among 162
      patients (247 eyes) who underwent this surgery, 77 (77 eyes) had unilateral
      surgery and 85 (170 eyes) bilateral. Twenty-seven (10.9%) of the 247 muscles had
      double bellies. Among all variables compared, only the incidence of fundus
      excyclotropia differed significantly between groups, occurring more often in eyes
      with double-bellied IO muscles (48% vs 27%; P =.041). The efficacy of weakening
      surgery in reducing overactions was similar in both groups. CONCLUSION: The
      finding that eyes with double-bellied IO muscles showed a higher incidence of
      fundus excyclotropia suggests that the presence of a second belly may alter the
      physiologic action of the IO muscle.

PMID- 11304814
TI  - Thickness of the retinal nerve fiber layer in amblyopic and normal eyes: a
      scanning laser polarimetry study.
AB  - PURPOSE: To compare scanning laser polarimeter (GDx, Laser Diagnostic
      Technologies, San Diego, Calif) measurements of the peripapillar retinal nerve
      fiber layer in amblyopic and normal eyes. METHODS: Scanning laser polarimetry was
      performed on 21 patients with unilateral strabismic amblyopia who had an absence
      of neurologic diseases or glaucoma and a minimum age of 7 years. A mean
      retardation map was calculated from separate scans or was considered to be the
      best scan obtained for each eye. Polarimetric indices were analyzed comparing
      amblyopic and contralateral normal eyes. RESULTS: The mean age was 15 +/- 9 years
      (7-35 years) and the male:female ratio was 13:8. There were 6 right and 15 left
      amblyopic eyes, with the amblyopic group having a mean visual acuity of 0.3 +/-
      0.1. The mean (+/- SD) indices did not differ significantly between normal and
      amblyopic eyes, except the number that summates information from the individual
      parameters, which was higher in normal (20.71 +/- 11.98) than in amblyopic (15.14
      +/- 6.81) eyes, P =.02. CONCLUSION: There was no statistical difference in
      thickness of the nerve fiber layer between amblyopic and normal eyes. A previous
      study found similar results in adults with strabismic amblyopia.

PMID- 11304815
TI  - Acquired nonaccommodative esotropia in childhood.
AB  - PURPOSE: Acquired nonaccommodative esotropia (ANAET) in childhood is reported to
      occur infrequently and is often associated with an underlying neurologic or
      neoplastic disorder. The primary objective of this study was to ascertain the
      prevalence and clinical characteristics of this form of childhood esotropia.
      METHODS: A cohort of all children younger than 11 years with esotropia from a
      predominantly rural Appalachian region was prospectively identified from August
      1, 1995, through July 31, 1998. The age at onset, family history of strabismus,
      perinatal and medical history, ophthalmologic findings, and surgical results were
      reviewed for all patients with ANAET. RESULTS: Twenty-three (10.4%) of 221
      consecutive children with esotropia were diagnosed with ANAET compared with 12
      (5.4%) diagnosed with congenital esotropia. The median age at esotropia onset for
      the 23 children with ANAET was 31.4 months (range, 8-63 months) with a mean
      initial angle of esotropia of 24 PD. Although at least 2 children presented with
      diplopia, none of the 23 patients were known to have harbored intracranial tumors
      or other lesions of the central nervous system during the follow-up period.
      Fourteen of the 19 patients who underwent surgery attended follow-up visits for
      at least 6 months after their last surgical procedure: 13 were within 8 PD or
      less of orthotropia, whereas the final patient had persistent esotropia. Twelve
      of the 13 patients within 8 PD of orthotropia demonstrated some level of
      stereopsis, including 2 children with bifoveal fixation. Two (10.5 %) of the 19
      operated patients later required a low hyperopic spectacle correction to control
      their deviation. CONCLUSIONS: ANAET was more prevalent than congenital esotropia
      in this cohort of children with esotropia. This clinically distinct form of
      strabismus typically begins between 1 and 5 years of age and appears to be
      infrequently associated with underlying disease. The angle of deviation is
      relatively small and early surgical correction is more likely to achieve bifoveal
      fixation for these patients than for those with congenital esotropia.

PMID- 11304816
TI  - Retinal and intraventricular cerebral hemorrhages in the preterm infant born at
      or before 30 weeks' gestation.
AB  - PURPOSE: To determine the prevalence of retinal hemorrhages and their association
      with cerebral intraventricular hemorrhages (IVH) in low-birth-weight preterm
      neonates born at or before 32 weeks' gestation. METHODS: We prospectively studied
      a consecutive series of 22 neonates (24-30 weeks' gestation; mean gestational
      age, 27 weeks; mean weight, 1065 g) admitted to the neonatal intensive care unit.
      Anterior segment and indirect ophthalmoscopic examination, as well as cranial
      ultrasonographic examination, were performed on day 1 and day 10 of life. The
      prevalence of retinal and intraventricular hemorrhage was tested statistically
      for association with obstetric and neonatal clinical variables. RESULTS: The
      prevalence of retinal hemorrhage was 9% (2/22; 95% CI, 3%-21%) on day 1 and 2%
      (1/22) on day 10. The prevalence of IVH was 27% (6/22; 95% CI, 9%-46%): 14%
      (3/22) on day 1 and 23% (5/22) on day 10. Retinal hemorrhages occurred with
      greater frequency in neonates born to women who had intrauterine infection
      (chorioamnionitis, P =.043) and low umbilical cord pH levels (P =.027). No
      association was found between the presence of retinal hemorrhage and IVH (P =
      1.000), mode of delivery (ie, vaginal vs cesarean section, P = 1.000), birth
      weight (P =.476), or gestational age (P = 1.000). The presence of subconjunctival
      hemorrhage was associated with IVH (P =.046). CONCLUSIONS: Retinal hemorrhages
      occur in less than 10% of low-birth-weight neonates, ie, a prevalence one half
      that observed in term neonates (22%). The hemorrhages tend to resolve without
      sequelae in the first 10 days of life and occur more commonly in infants born to
      women with uterine infection. Retinal hemorrhages in very premature neonates are
      not predictive of IVH-related brain damage.

PMID- 11304817
TI  - The use of subtenon ropivacaine in managing strabismus with adjustable sutures.
AB  - BACKGROUND: Squint angle alterations with the use of adjustable sutures after
      strabismus surgery can be painful. Ropivacaine is a long-acting local anesthetic
      that, at low doses, produces sensory block with limited nonprogressive motor
      block. METHOD: We performed a double-blind, randomized, pilot study using
      subtenon ropivacaine or placebo at the time of surgery in patients undergoing
      adjustable suture surgery. Surgery was performed by the same surgeon in each
      case. Later in the day, the same surgeon adjusted the sutures. At the time of
      adjustment, the patient recorded pain using a linear pain score, and the surgeon
      recorded ease of adjustment using a linear score. The results of surgery were
      noted at 4 weeks. RESULTS: Ten patients were randomized to receive ropivacaine
      and 11 to receive placebo. All 10 of the ropivacaine group and 9 of the placebo
      group had suture adjustment. In the ropivacaine group, there was a significantly
      lower pain score (P <.05, Mann-Whitney U test) but no significant difference in
      ease of adjustment. There appeared to be no demonstrable difference in the
      results of surgery between the 2 groups. CONCLUSION: Ropivacaine appears to
      reduce the pain of postoperative suture adjustment without adversely affecting
      the final outcome, although it does not appear to ease the adjustment itself.
      This small pilot study shows promising results in postoperative analgesia in
      these patients, although further larger trials are recommended.

PMID- 11304818
TI  - Stereopsis in patients with albinism: clinical correlates.
AB  - PURPOSE: A hallmark of albinism is excessive decussation of retinostriate
      projections at the optic chiasm. This misprojection might lead to abnormalities
      in the retinal correspondence and may account for the usual absence of
      stereovision. We report on 2 groups of patients with albinism who have either
      fine or gross stereopsis and compare the clinical findings of these groups to
      other patients with albinism with similar visual acuities but no stereopsis.
      METHODS: A retrospective chart review of patients with albinism was used to
      segregate those with a letter visual acuity of 20/100 or better in one eye,
      assessment of stereopsis, and strabismus < or = 10 PD. Forty-five patients were
      identified. Albinism type, best-corrected visual acuity, motility, Titmus
      vectograph stereoacuity, iris and macula transparency grades, and the presence or
      absence of both melanin and an annular reflex in the macula were tabulated. A
      comparison of the clinical characteristics of the groups with and without
      stereopsis was made. RESULTS: Those albino subjects who demonstrated stereopsis
      had better visual acuity, less iris transillumination, more frequent presence of
      melanin in the macula, less nystagmus, and less marked foveal hypoplasia than the
      albino subjects without stereopsis. No nystagmus was clinically detected in 5
      patients with fine stereopsis. All these differences were statistically
      significant. Macular transparency grade was not significantly different between
      the groups. CONCLUSIONS: Patients with albinism who demonstrate stereopsis tend
      to have better visual acuity, more iris pigment, and more melanin pigment in the
      macula than their counterparts without stereopsis.

PMID- 11304819
TI  - Vertical rectus muscle augmented transposition in Duane syndrome.
AB  - INTRODUCTION: Reduction or elimination of face turn and esotropia in the primary
      position while maintaining the largest possible diplopia-free field are the major
      surgical goals in Duane syndrome with esotropia. Unsatisfactory postoperative
      results may occur because of limitation in adduction, poor abduction, or induced
      vertical deviations. Recent reports have shown enhanced results from rectus
      muscle transposition techniques when a lateral posterior augmentation fixation is
      placed. METHODS: Preoperative and postoperative data of 2 groups of subjects who
      had Duane syndrome with esotropia in primary position and markedly reduced
      abduction were comparatively analyzed. Group A consisted of subjects who had
      transposition of both vertical rectus muscles to the lateral rectus muscle with a
      posterior lateral augmentation suture placed in each transposed muscle. Group B
      subjects had transposition of both vertical rectus muscles to the lateral rectus
      muscle without the posterior lateral augmentation suture. RESULTS: A total of 32
      subjects in group A and 22 subjects in group B were analyzed. In group A,
      anomalous head position improved 19.1 degrees +/- 10.3 degrees compared with
      group B subjects who improved 10.6 degrees +/- 5.8 degrees (P <.05). In group A,
      esotropia in primary position improved 16.4 +/- 9.2 PD compared with group B
      subjects who improved 8.5 +/- 6.9 PD (P <.05). CONCLUSIONS: Subjects with Duane
      syndrome and esotropia in primary position who had undergone augmented
      transposition of the vertical rectus muscles obtained improved head position and
      better alignment in primary position and had a reduction in the incidence of
      reoperation for undercorrection when compared with similar patients who had
      undergone vertical rectus muscle transposition without posterior lateral
      augmentation sutures.

PMID- 11304820
TI  - SITA visual field testing in children.
AB  - PURPOSE: The Swedish Interactive Thresholding Algorithm (SITA) is a new testing
      strategy for the Humphrey perimeter. The standard SITA algorithm shortens test
      time in adults without increasing variability, but its usefulness for detecting
      field defects in children has not been investigated. METHODS: We evaluated 92
      standard SITA 24-2 visual fields of children, most of whom had various types of
      optic neuropathies (pediatric idiopathic intracranial hypertension, homonymous
      defects, bitemporal defects, papilledema from brain tumors), and compared them
      with 49 full threshold 24-2 fields obtained in similar patients. We evaluated
      outcome measures of foveal threshold, mean defect, pattern standard deviation,
      false-negative and false-positive rates, and test time. Five children (9 eyes)
      had both SITA and full threshold testing (FTT). RESULTS: The SITA decreased test
      time by over 50% compared with FTT (12.6 +/- 3.0 minutes vs 6.6 +/- 1.6 minutes
      [P <.00001]). When patients with field defects were eliminated, the pattern
      standard deviation was lower with SITA than FTT (P <.002), indicating lower
      intratest variability of SITA in subjects with normal fields. No detectable
      difference was observed in the other outcome measures. Subjective analysis of
      gray-scale fields in patients who underwent testing with the use of both
      strategies showed marked similarities. CONCLUSIONS: SITA shortens test time
      significantly compared with FTT and does so without jeopardizing
      interpretability. SITA has less intratest variability than FTT and therefore
      should be better for detecting and following defects. Caution is advised when
      following a visual field defect unless the same strategy is used for each
      evaluation. Switching strategies in the absence of a stable field defect is not
      recommended.

PMID- 11304821
TI  - Decreased incidence of retinopathy of prematurity, 1995-1997.
AB  - PURPOSE: To report a significant decrease in the incidence of retinopathy of
      prematurity (ROP), both in our neonatal intensive care unit (NICU) and
      internationally, and review factors in patient care that may be contributory.
      METHODS: We retrospectively reviewed the records of all neonates weighing less
      than 1251 g admitted to our NICU from 1995 to 1997 and evaluated the incidence
      and stage of ROP. These data on 191 neonates were compared with an international
      NICU database of 9989 similar neonates, which represents all infants who received
      an ophthalmologic examination in the Vermont-Oxford Network Database (VOND) in
      1997, except those from our institute (the University of Kentucky). In addition
      to investigating the incidence of ROP, we looked at the use of antenatal
      corticosteroids given 1 to 7 days prepartum, the use of oxygen at 36 weeks'
      postconceptional age, and the use of oxygen at home upon discharge. RESULTS: In
      our center, we had a 36.1% incidence of ROP compared with an international
      incidence of 57.2% for the VOND in 1997 (P <.0001). Antenatal corticosteroids
      were given to 62.6% of infants in our center compared with 48.6% in the VOND (P
      <.005). In addition, 48.5% of our infants weighing less than 1500 g received
      oxygen at 36 weeks' postconceptional age versus 29.5% of the VOND infants (P
      <.001). Upon discharge to home, 37.5% of our infants were on oxygen compared with
      15.6% of infants from all VOND centers, excluding the University of Kentucky (P
      <.001). CONCLUSION: The incidence of ROP in our center from 1995 to 1997 and in
      the VOND in 1997 show a significant decrease from the 65.8% incidence from 1986
      to 1987 reported by the Multicenter Trial of Cryotherapy for ROP.

PMID- 11304822
TI  - A rare case of bilateral dissociated hypotropia and unilateral dissociated
      esotropia.

PMID- 11304823
TI  - Bilateral simultaneous retinal arteriolar obstruction in a child with hemoglobin
      SS sickle cell disease.

PMID- 11304824
TI  - Hemorrhagic glaucoma in an infant with hemophilia, spontaneous hyphema, aniridia,
      and persistent iris vessels.

PMID- 11304825
TI  - Impact of overlapping recruitment on psychiatric genetic studies.

PMID- 11304826
TI  - Impact of overlapping recruitment on linkage analysis of complex disorders:
      simulation studies.
AB  - Evidence for significant linkage in complexly inherited disorders usually
      necessitates independent, replicative studies. This study investigates the
      implications of including in the replicative studies families already used to
      suggest linkage in initial linkage analysis. We generated 1,000 unlinked
      replicates of 100 nuclear families with a complexly inherited disease but with no
      linkage to the markers analyzed. We then used a standard nonparametric linkage
      method to analyze these data. From the original 1,000 replicates of the original
      data set, one set was chosen as it yielded suggestive, but falsely positive,
      linkage results (LOD score = 3.4). Variable numbers of randomly selected families
      from this positive replicate (n = 100 families) were used to replace families in
      replicates of the original (unlinked) data set, and linkage analysis repeated.
      Overlap of families from the "positive data set" did increase the LOD scores for
      "unlinked data sets." While a small amount of overlap (replacement) between a
      positive linkage result and the replication sample is unlikely in practice to
      alter results, our study suggests that steps should be taken to ensure that
      overlap is minimized. The implications of this overlapping recruitment on
      replicative linkage studies are discussed.

PMID- 11304827
TI  - Evidence for linkage disequilibrium between the dopamine transporter and bipolar
      disorder.
AB  - A role for the dopamine transporter (DAT) in bipolar disorder is implicated by
      several lines of pharmacological evidence, as well as suggestive evidence of
      linkage at this locus, which we have reported previously. In an attempt to
      identify functional mutations within DAT contributing a susceptibility to bipolar
      disorder, we have screened the entire coding region, as well as significant
      portions of the adjacent non-coding sequence. Though we have not found a
      definitive functional mutation, we have identified a number of single nucleotide
      polymorphisms (SNPs) that span the gene from the distal promoter through exon 15.
      Of the 39 SNPs that are suitable for linkage disequilibrium (LD) studies, 14 have
      been analyzed by allele-specific PCR in a sample of 50 parent-proband triads with
      bipolar disorder. A haplotyped marker comprised of five SNPs, spanning the region
      between exon 9 and exon 15, was constructed for each individual, and
      transmission/disequilibrium test (TDT) analysis revealed this haplotype to be in
      linkage disequilibrium with bipolar disorder (allele-wise TDT p = 0.001, genotype
      wise TDT p = 0.0004). These data replicate our previous finding of linkage to
      markers within and near DAT in a largely different family set, and provide
      further evidence for a role of DAT in bipolar disorder. Published 2001 Wiley
      Liss. Inc.

PMID- 11304828
TI  - Markers close to the dopamine D5 receptor gene (DRD5) show significant
      association with schizophrenia but not bipolar disorder.
AB  - Following the description of linkage of markers at chromosome 4p16 to bipolar
      disorder in several families [Blackwood et al., 1996], and the association of the
      alleles of a polymorphism closely linked to D5 dopamine receptor gene with
      schizophrenia [Williams et al., 1997], we have looked for linkage disequilibrium
      between a series of microsatellite markers from this region and major psychoses
      including schizophrenia, bipolar disorder, and unipolar major depressive
      disorder. A significant increase in the frequency of the 148 bp allele of DRD5 (P
      = 0.024) and the 244 bp allele of D4S615 (P = 0.001) was found in patients with
      schizophrenia (n = 158 DRD5; n = 133 D4S615), compared with patients with bipolar
      disorder (n = 270 DRD5; n = 107 D4S615), or controls without psychiatric illness
      (n = 437 DRD5; n = 309 D4S615). The frequency of the 148 bp allele of DRD5 was
      also increased in schizophrenia over unipolar major depressive disorder (n = 65).
      D4S615 was not typed in unipolar disorder. The estimated odds ratios confirmed
      that the 148 bp allele of DRD5 and the 244 bp allele of D4S615 conferred
      increased risk of schizophrenia. Estimated Haplotype (EH) analysis of 174
      controls and 128 patients with schizophrenia who were typed for both markers
      confirmed the strong associations with these alleles but did not show evidence
      that the markers were in linkage disequilibrium with each other even though they
      lie approximately 150 kb apart. The data are consistent with an association
      between markers close to the D5 dopamine receptor and schizophrenia, but not
      bipolar disorder or unipolar major depression.

PMID- 11304829
TI  - Linkage study of the alpha2A adrenergic receptor in attention-deficit
      hyperactivity disorder families.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric
      disorder, characterized by marked and pervasive inattention, hyperactivity, and
      impulsiveness. An alteration in the expression or function of the adrenergic
      system has been suggested to be involved in ADHD based on animal models,
      pharmacological interventions, and the neural circuitry of attentional processes.
      The efficacy of clonidine in reducing disruptive behaviors in some children with
      ADHD argues for a causal role of the adrenergic system and more specifically for
      the alpha2A receptors as clonidine is an alpha2A agonist that inhibits release of
      noradrenaline into the synapse. In animal studies, alpha2A receptor agonists have
      also been shown to improve performance on working memory tasks under distracting
      conditions, indicating that these receptors function in the regulation of
      attention. We examined the possibility that the gene for the alpha2A adrenergic
      receptor (ADRA2A) is linked to ADHD by testing a polymorphism located in the
      promoter region of the ADRA2A gene in a sample of 94 nuclear families with an
      ADHD proband. We found no evidence for linkage of the ADRA2A gene with ADHD,
      using the transmission disequilibrium test in this set of families.

PMID- 11304830
TI  - Further evidence for linkage of Gilles de la Tourette syndrome (GTS)
      susceptibility loci on chromosomes 2p11, 8q22 and 11q23-24 in South African
      Afrikaners.
AB  - Utilizing DNA samples from 91 Afrikaner nuclear families with one or more
      affected children, five genomic regions on chromosomes 2p, 8q, 11q, 20q, and 21q
      that gave evidence for association with GTS in previous case-control association
      studies were investigated for linkage and association with GTS. Highly
      polymorphic markers with mean heterozygosity of 0.77 were typed and resulting
      genotypes evaluated using single marker transmission disequilibrium (TDT), single
      marker haplotype relative risk (HRR), and multi-marker "extended" TDT and HRR
      methods. Single marker TDT analysis showed evidence for linkage or association,
      with p-values near 0.05, for markers D2S139, GATA28F12, and D11S1377 on
      chromosomes 2p11, 8q22 and 11q23-24, respectively. Extended, two-locus TDT and
      HRR analysis provided further evidence for linkage or association on chromosome 2
      with p-values of 0.007 and 0.025, and chromosome 8 with p-values of 0.059 and
      0.013, respectively. These results provide important additional evidence for the
      location of GTS susceptibility loci.

PMID- 11304831
TI  - Association analysis of the functional monoamine oxidase A gene promoter
      polymorphism in psychiatric disorders.
AB  - Functional characterization studies revealed that transcriptional activity of the
      human monoamine oxidase A (MAOA) gene is modulated by a polymorphic repetitive
      sequence located approximately 1.2 kb upstream of the ATG codon. To investigate
      the possible influence of the allelic variants of the MAOA gene-linked
      polymorphic region (MAOA-LPR) on the genetic predisposition to psychiatric
      disorders, we have performed a case-control association study. 174 patients with
      affective disorders and 258 patients with schizophrenia according to DSM-IV, as
      well as 229 population controls were tested. Statistical analysis showed no
      significant differences in allele or genotype frequencies between control and
      patient groups. Our results suggest that there is no association between MAOA-LPR
      genotype and susceptibility to recurrent major depression, bipolar disorder, and
      schizophrenia in our population.

PMID- 11304832
TI  - No association of two missense variations of the benzodiazepine receptor
      (peripheral) gene and mood disorders in a Japanese sample.
AB  - The benzodiazepine receptor (peripheral) (BZRP) plays an important role in the
      steroid syntheses of the adrenal glands and brain, which is possibly involved in
      the pathophysiology of mood disorders. We evaluated an association study between
      two missense variations of the BZRP gene and mood disorders in a Japanese sample.
      However, no statistically significant associations with either bipolar disorders
      or depressive disorders were observed in the allele frequencies, genotype counts,
      or haplotype distributions for the two variations, although the present sample
      size had a moderate power (0.46-0.86). These results do not suggest that the BZRP
      gene plays a role in the genetic predisposition of affective disorders.

PMID- 11304833
TI  - Association analysis between two functional dopamine D2 receptor gene
      polymorphisms and schizophrenia.
AB  - The dopamine D2 receptor (DRD2) gene has been listed as one of the candidate
      genes for susceptibility to schizophrenia. To date, a significant association
      between schizophrenia and two functional DRD2 gene polymorphisms, Ser311Cys and 
      141C Ins/Del, in Japanese samples, has been reported by Arinami et al. [1994:
      Lancet 343:703-704; 1997: Hum Mol Genet 6:577-582]. In the present study, we
      replicated the findings of Arinami et al. [1994: Lancet 343:703-704; 1997: Hum
      Mol Genet 6:577-582] in the same ethnic groups (Japanese samples) with the same
      polymorphisms (Ser311Cys and -141C Ins/Del). We genotyped these two polymorphisms
      for 241 patients and for 201 controls. Neither polymorphism was associated with
      schizophrenia. Moreover, in a haplotype analysis of the present sample, combined
      pairs of two polymorphisms provided no evidence for the association of either
      haplotype with schizophrenia. Our findings indicate that an association between
      the two functional DRD2 gene polymorphisms, Ser311Cys and -141C Ins/Del, and
      schizophrenia is unlikely.

PMID- 11304834
TI  - Non-replication of association between cathepsin D genotype and late onset
      Alzheimer disease.
AB  - In two recent studies from Germany, a strong association was found between the
      allelic variant T of the amino acid substitution encoding polymorphism 224 C/T
      (A38V) in exon 2 of the cathepsin D gene (CTSD) and late onset Alzheimer disease
      (AD). Other studies from Europe and the USA revealed ambiguous results.
      Therefore, we performed an independent association study on CTSD and AD in a
      sample of 324 Caucasian patients from Germany, Switzerland, and Italy with late
      onset AD, and 302 non-demented controls. We could not confirm an association
      between CTSD genotype and AD, although there was a slight but not significant
      increase in frequency of the T allele and T carrier status in AD. Post hoc data
      analyses suggested that there might be a stronger effect of CTSD genotype on AD
      risk in males, and an interaction between CTSD and APOE genotypes in males but
      not females.

PMID- 11304835
TI  - Single or multiple familial cognitive risk factors in schizophrenia?
AB  - The fact that relatives of patients with schizophrenia display subtle cognitive
      abnormalities suggests genetic transmission of an underlying cognitive
      endophenotype. It was examined to what extent the cognitive abnormalities that
      discriminate patients and relatives from controls do so independently of each
      other, and independent of IQ. Neuropsychological measures were assessed in 50
      patients with schizophrenia, 50 first-degree relatives of patients with
      schizophrenia, and 50 healthy controls. The assessment focused on episodic
      memory, attentional span, simple and complex speed of information, and semantic
      memory. Factor analysis of the cognitive test results yielded four factors
      reflecting speed, episodic memory, working memory, and semantic fluency.
      Performance of the relatives was intermediate to that of the patients and the
      controls after adjustment for age, sex, educational level, and IQ. For both
      patients and relatives, speed of information processing, working memory, and
      episodic memory independently discriminated from control performance, with a
      similar pattern in the order of the size of the effects. The results suggest the
      existence of more than one familial cognitive risk factor for schizophrenia.
      Independent familial cognitive risk factors may represent separate causal
      influences or separate indicators of risk related to the same genetic mechanism.

PMID- 11304836
TI  - A follow-up linkage study supports evidence for a bipolar affective disorder
      locus on chromosome 21q22.
AB  - Evidence for linkage between bipolar affective disorder (BP) and 21q22 was first
      reported by our group in a single large pedigree with a lod score of 3.41 with
      the PFKL locus. In a subsequent study, with denser marker coverage in 40
      multiplex BP pedigrees, we reported supporting evidence with a two-point lod
      score of 2.76 at the D21S1260 locus, about 6 cM proximal to PFKL. For cost
      efficiency, the individuals genotyped in that study comprised a subset of our
      large pedigree sample. To augment our previous analysis, we now report a follow
      up study including a larger sample set with an additional 331 typed individuals
      from the original 40 families, improved marker coverage, and an additional 16
      pedigrees. The analysis of all 56 pedigrees (a total of 862 genotyped individuals
      vs. the 372 genotyped previously), the largest multigenerational BP pedigree
      sample reportedly analyzed to date, supports our previous results, with a two
      point lod score of 3.56 with D21S1260. The 16 new pedigrees analyzed separately
      gave a maximum two-point lod score of 1.89 at D21S266, less than 1 cM proximal to
      D21S1260. Our results are consistent with a putative BP locus on 21q22.

PMID- 11304837
TI  - Targeted genome screen of panic disorder and anxiety disorder proneness using
      homology to murine QTL regions.
AB  - Family and twin studies have indicated that genes influence susceptibility to
      panic and phobic anxiety disorders, but the location of the genes involved
      remains unknown. Animal models can simplify gene-mapping efforts by overcoming
      problems that complicate human pedigree studies including genetic heterogeneity
      and high phenocopy rates. Homology between rodent and human genomes can be
      exploited to map human genes underlying complex traits. We used regions
      identified by quantitative trait locus (QTL)-mapping of anxiety phenotypes in
      mice to guide a linkage analysis of a large multiplex pedigree (99 members, 75
      genotyped) segregating panic disorder/agoraphobia. Two phenotypes were studied:
      panic disorder/agoraphobia and a phenotype ("D-type") designed to capture early
      onset susceptibility to anxiety disorders. A total of 99 markers across 11
      chromosomal regions were typed. Parametric lod score analysis provided suggestive
      evidence of linkage (lod = 2.38) to a locus on chromosome 10q under a dominant
      model with reduced penetrance for the anxiety-proneness (D-type) phenotype.
      Nonparametric (NPL) analysis provided evidence of linkage for panic
      disorder/agoraphobia to a locus on chromosome 12q13 (NPL = 4.96, P = 0.006).
      Modest evidence of linkage by NPL analysis was also found for the D-type
      phenotype to a region of chromosome 1q (peak NPL = 2.05, P = 0.035). While these
      linkage results are merely suggestive, this study illustrates the potential
      advantages of using mouse gene-mapping results and exploring alternative
      phenotype definitions in linkage studies of anxiety disorder.

PMID- 11304839
TI  - Polymorphism in the cell division cycle 45 like gene and schizophrenia.

PMID- 11304838
TI  - Genome screening for linkage disequilibrium in a Costa Rican sample of patients
      with bipolar-I disorder: a follow-up study on chromosome 18.
AB  - Linkage disequilibrium (LD) methods offer great promise for mapping complex
      traits, but have thus far been applied sparingly. In this paper we describe an LD
      mapping study of severe bipolar disorder (BP-I) in the genetically isolated
      population of the Central Valley of Costa Rica. This study provides the first
      complete screen of a chromosome for a complex trait using LD mapping and presents
      the first application of a new LD mapping statistic (ancestral haplotype
      reconstruction (AHR)) that evaluates haplotype sharing among affected
      individuals. The results of this chromosome-wide analysis are instructive for
      genome-wide LD mapping in isolated populations. Furthermore, the analysis
      continues to support a possible BP-I locus on 18pter, suggested by previous
      analyses in this population. Evidence for a possible BP-I locus on 18q12.2 is
      also described.

PMID- 11304840
TI  - Association between atopic disorders and depression: findings from the Northern
      Finland 1966 birth cohort study.

PMID- 11304842
TI  - Heparin induced thrombocytopenia thrombosis (HIT/T) syndrome: diagnosis and
      treatment.
AB  - Heparin induced thrombocytopenia thrombosis (HIT/T) is associated with a high
      morbidity and mortality. Diagnosis is essentially clinical and negative results
      of laboratory assays do not exclude the diagnosis. Treatment involves stopping
      all heparin immediately and giving an alternative thrombin inhibitor. The
      adoption of low molecular weight heparins is one reason for the reduced incidence
      of this disease in recent years.

PMID- 11304841
TI  - Pulmonary preinvasive neoplasia.
AB  - Advances in molecular biology have increased our knowledge of the biology of
      preneoplastic lesions in the human lung. The recently published WHO lung tumour
      classification defines three separate lesions that are regarded as preinvasive
      neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2)
      atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary
      neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages
      (mild, moderate, severe, and CIS), based upon the distribution of atypical cells
      and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades;
      many epithelia are hard to assess and the reproducibility of this complex system
      remains to be established. Detailed criteria are, however, welcome and provide an
      objective framework on which to compare various molecular changes. Alterations in
      gene expression and chromosome structure known to be associated with malignant
      transformation can be demonstrated in CIS, less so in dysplasias, but also in
      morphologically normal epithelium. The changes might be sequential, and their
      frequency and number increase with atypia. Less is known of the "risk of
      progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take
      between one and 10 years for invasion to occur, yet the lesion(s) may be
      reversible if carcinogen exposure ceases. AAH may be an important precursor
      lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in
      an adenoma-carcinoma sequence. There is good morphological evidence that AAH may
      progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non
      invasive lesion by definition). Invasion then develops within BAC and peripheral
      lung adenocarcinoma evolves. The molecular events associated with this
      progression are not well understood and studies are hampered by a lack of clear
      criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the
      patterns of expression of tumour associated genes are consistent with neoplastic
      progression. We have little idea of the incidence of AAH in the normal or
      "smoking" populations. It is found more frequently in cancer bearing lungs,
      especially in those with adenocarcinoma, and is more common in women. No data are
      available on the risk of progression of AAH. DIPNECH is an exceptionally rare
      lesion associated with the development of multiple carcinoid tumours. Almost
      nothing is known of its biology. Knowledge of these lesions will be crucial in
      the design and understanding of lung cancer screening programmes, where it is
      likely that the morphological and, more importantly perhaps, the molecular
      characteristics of these lesions will provide useful targets for detection and
      possibly even treatment.

PMID- 11304843
TI  - Vasculitides associated with HIV infection.
AB  - The manifestations of human immunodeficiency virus (HIV) infection are protean
      and vasculitides are one of the less common but nonetheless important
      consequences. A wide range of vasculitides can be encountered, ranging from
      vasculitis resulting from specific infective agents to a non-specific vasculitis.
      Among the infective causes, cytomegalovirus and tuberculosis are probably the
      most common. A polyarteritis nodosa-like vasculitis with important differences to
      classic polyarteritis nodosa is also described. Hypersensitivity vasculitis
      resulting in several patterns of vasculitis and angiocentric immunoproliferative
      vasculitis are well recognised. As part of the immunocompromise caused by HIV, a
      granulomatous inflammation involving small arteries and veins of the brain
      surface and leptomeninges, termed a primary angiitis of the central nervous
      system, is a rare vasculitis associated with high mortality. A recently described
      large vessel (aorta, femorals, carotids) vasculopathy resulting in either
      multiple aneurysm formation or occlusive disease is seen in young adults. An
      infective agent is not found but aetiologically some of these lesions might be
      the result of a leucocytoclastic vasculitis of vasa vasora or periadventitial
      vessels. A final group of non-specific vasculitides not fitting into any of the
      characteristic patterns described accounts for the residue of vasculitides
      associated with HIV.

PMID- 11304844
TI  - Are coroners' necropsies necessary? A prospective study examining whether a "view
      and grant" system of death certification could be introduced into England and
      Wales.
AB  - AIMS: To determine whether the cause of death could be accurately predicted
      without the need for a necropsy, and thus to consider whether a "view and grant"
      system of issuing a cause of death could be introduced into England and Wales.
      METHOD: A one year prospective necropsy study was performed incorporating 568
      deaths. Before necropsy, in each case the cause of death was predicted from the
      available history without examination of the body, and this cause was then
      compared with the cause of death found at necropsy. RESULTS: The ability of the
      pathologist involved in the study to predict a cause of death before necropsy,
      either while in the mortuary or as a paper exercise, was shown to vary between
      61% and 74% of cases. After the necropsy, the number of correct predicted causes
      of death ranged from 39% to 46%. Ischaemic heart disease was found to be the most
      common and most accurately predicted cause of death. Some natural diseases were
      frequently misdiagnosed, whereas certain types of unnatural disease were always
      identified correctly. CONCLUSIONS: This study highlights the advantages and
      disadvantages of a view and grant system. Although it identifies a potential use
      of such a system, in some cases such as natural cardiac disease, because of the
      potentially high diagnostic error rate, the continuation of the present system of
      postmortem examination as part of the coroner's enquiry is recommended.

PMID- 11304845
TI  - Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical
      localisation and in vitro effects on cytokine secretion.
AB  - BACKGROUND/AIMS: Interleukin 10 (IL-10) is a counter-inflammatory peptide
      implicated in the downregulation of human intestinal immune responses. Enhanced
      secretion of IL-10 has been documented in gastric biopsy organ culture in
      Helicobacter pylori infection. This study aimed to define the cellular origins of
      IL-10 in H pylori associated gastritis, and to determine the effects of
      endogenous IL-10 on proinflammatory cytokine secretion in vitro. METHODS:
      Endoscopic biopsies were obtained from the gastric antrum at endoscopy from
      patients with dyspepsia. Two pairs of antral biopsies were cultured in vitro for
      24 hours, one pair in the presence of neutralising anti-IL-10 monoclonal
      antibody, the other pair as controls. The cytokine content of culture
      supernatants (tumour necrosis factor alpha (TNF-alpha), IL-6, and IL-8) was
      determined by enzyme linked immunosorbent assay and corrected for biopsy weight.
      Helicobacter pylori status was established by histology and biopsy urease test,
      and histopathology graded by the Sydney system. In a subgroup of patients,
      western blotting was used to establish CagA serological status.
      Immunohistochemistry for IL-10 was performed on formalin fixed tissues using a
      combination of microwave antigen retrieval and the indirect avidin-biotin
      technique. Immunoreactivity was scored semiquantitatively. RESULTS: In vitro
      culture was performed in 41 patients: 31 with H pylori positive chronic gastritis
      and 10 H pylori negative. In vitro secretion of TNF-alpha, IL-6, and IL-8 for
      "control" biopsies was significantly higher in H pylori positive versus negative
      samples, with values of TNF-alpha and IL-6 correlating with the degree of active
      and chronic inflammation and being higher in CagA seropositive cases. No evidence
      for enhanced cytokine secretion was seen in biopsies cocultured in the presence
      of anti-IL-10 monoclonal antibody. Immunohistochemistry was performed in 29
      patients, of whom 13 were H pylori positive. IL-10 immunoreactivity was observed
      in the surface epithelium in all H pylori positive cases and in 13 of 16 negative
      cases, especially in areas of surface epithelial degeneration. Lamina propria
      mononuclear cells (LPMNCs) were positively stained in all H pylori positive cases
      and in 12 of 16 negative cases, with a significantly greater proportion of
      positive LPMNCs in the positive group. CONCLUSIONS: This study localised IL-10
      protein to the gastric epithelium and LPMNCs. In vitro proinflammatory cytokine
      secretion was increased in H pylori infection (especially CagA positive
      infection), but blocking endogenous IL-10 secretion did not significantly
      increase cytokine secretion. IL-10 is implicated in H pylori infection and might
      "damp down" local inflammation. The role of gastric IL-10 secretion in
      determining the clinicopathological outcome of infection merits further study.

PMID- 11304846
TI  - The physiological expression of inducible nitric oxide synthase (iNOS) in the
      human colon.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed in the colonic
      epithelium in both inflammatory bowel disease and colorectal cancer. Nitric oxide
      (NO), the product of this enzyme, has been implicated in the pathogenesis of both
      conditions. However, there are conflicting data on whether iNOS is expressed in
      the normal, uninflamed human colon. AIMS: To evaluate the expression of iNOS in
      histologically normal, non-inflamed human colonic mucosa. PATIENTS/METHODS:
      Reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and
      immunohistochemistry were used to investigate the expression of iNOS in 17
      histologically normal specimens obtained at colectomy performed for colorectal
      neoplasia. In addition, 16 endoscopic mucosal biopsies, taken from normal
      individuals, were also evaluated. Eleven surgical specimens and 16 endoscopic
      biopsies from patients with refractory ulcerative colitis were used as
      inflammatory controls. RESULTS: All types of specimens expressed iNOS mRNA.
      Immunoblotting revealed a protein of approximately 130 kDa consistent with iNOS
      in mucosal extracts of 77% of normal individuals, and 85% of diseased controls.
      Immunolabelling localised this protein to the surface epithelium in most of the
      normal specimens and also to the crypt epithelium and inflammatory cells in the
      diseased controls. CONCLUSIONS: These findings provide evidence that iNOS is
      often expressed in the surface epithelium of non-inflamed human colon, suggesting
      that it is induced by local luminal factors, such as bacterial lipopolysaccharide
      (endotoxin). The resultant NO produced at this site might act as an oxidative
      barrier, reducing bacterial translocation and providing a means of defence
      against pathogenic microorganisms.

PMID- 11304848
TI  - HPV detection and measurement of HPV-16, telomerase, and survivin transcripts in
      colposcopy clinic patients.
AB  - AIMS: To determine whether the detection of high risk human papillomavirus (HPV)
      types is more predictive for high grade CIN than the current cervical smear test,
      and whether the production and measurement of HPV type 16 (HPV-16) and cellular
      survivin and telomerase transcripts can be used to discriminate between cervical
      HPV infections that self cure and those that induce high grade lesions. METHODS:
      Three hundred and fifty four cervical smear samples from women attending the
      colposcopy clinic were tested by the polymerase chain reaction (PCR) for the
      presence of HPV. Transcripts for HPV-16 E6, E6*I, E6*II, E7, and L1 as well as
      cellular survivin, telomerase RNA component, and telomerase reverse transcriptase
      were measured using fluorogenic probe (Taqman) assays. RESULTS: Referral smear
      grades of severe or moderate showed greater positive predictive values for CIN
      2/3 than did the detection of high or moderate risk HPV types. HPV-16 transcripts
      from E6, E6*I, E6*II, and E7 showed high predictive values for CIN 2/3, but low
      sensitivity. The telomerase RNA component was detected in 53 of 57 samples and
      telomerase reverse transcriptase was only detected in one sample, whereas
      survivin transcripts were detected in 40% of samples. CONCLUSIONS: The detection
      of HPV-16 or cellular survivin or telomerase transcripts did not accurately
      predict the grade of CIN in the samples. The detection of HPV risk types
      correlated well with the grade of CIN; however, the referral grade smear was the
      most accurate predictor of the severity of the lesion. Of the 35 different HPV
      types detected, 18 are not included in the HPV hybrid capture II commercial test
      kit. The use of such kits would have missed HPV infection in 4.3% of clinic
      patients with CIN 2/3 lesions and 15.4% with CIN 0/1.

PMID- 11304847
TI  - Cytotoxic T cells in AIDS colonic cryptosporidiosis.
AB  - BACKGROUND/AIMS: It is not known how enteric cryptosporidiosis induces severe
      intestinal impairment despite minimal invasion by the parasite. The aim of this
      study was to analyse the histological features and locally implicated immune
      cells in colonic biopsies of AIDS related cryptosporidiosis. PATIENTS/METHODS:
      Colonic biopsies from patients with AIDS related cryptosporidiosis (n = 10, group
      I), patients with AIDS but without intestinal infection (n = 9, group II), and
      human seronegative controls (n = 9, group III) were studied. Using
      immunohistochemistry the infiltrating mononuclear cells were analysed in both the
      epithelium and lamina propria for the expression of CD3, CD8, TiA1, granzyme B,
      and CD68 and for glandular expression of human major histocompatibility complex
      DR antigen (HLA-DR). RESULTS: Severe histological changes, resulting in abundant
      crypt epithelial apoptosis and inflammatory infiltrate in the lamina propria,
      were seen in all biopsies from group I. A significant increase of CD8+, TiA1+,
      and granzyme B+ T cells in the lamina propria and HLA-DR glandular expression was
      noted in group I compared with groups II and III. However, the number of
      intraepithelial lymphocytes, lamina propria CD3+ T cells, and macrophages was not
      significantly increased in cryptosporidiosis specimens compared with controls.
      CONCLUSION: Epithelial apoptosis mediated by granzyme B+ cytotoxic host T cells
      might play a major role in the development of colonic lesions in AIDS related
      cryptosporidiosis.

PMID- 11304849
TI  - Predictive value of topoisomerase II alpha immunostaining in urothelial bladder
      carcinoma.
AB  - AIMS: The nuclear enzyme DNA topoisomerase II has been shown to be required for
      chromatin condensation and chromosomal segregation during mitosis; its isoform
      topo II alpha is linked with active cell proliferation in mammalian cells. The
      aim of this study was to examine the relation of the expression of topo II alpha
      to the biological behaviour of conventional urinary bladder cancer. METHODS:
      Formalin fixed, paraffin wax embedded tissue from 94 specimens of bladder
      urothelial cancer were immuno-histochemically stained for topo II alpha. For each
      case, a topo II alpha index was determined. A similar index had been determined
      for Ki-67, a known cell proliferation marker. Each case had also been graded,
      staged, and evaluated for DNA ploidy as well as for p53 and bcl-2
      immunoreactivity. RESULTS: Raised topo II alpha expression (in > or = 10% of
      malignant nuclei) correlated with two adverse prognosticators--high grade (p =
      0.027) and invasion of the muscularis propria (p = 0.013), but with no other
      evaluated parameter. By multivariate survival analysis using Cox's proportional
      hazard model, high expression of topo II alpha was found to be predictive for
      worse survival (p = 0.0047). Patients' age, tumour stage, and grade were also
      retained as independent prognostic factors (p = 0.0349, p = 0.00005, and p =
      0.0130, respectively). The negative influence of increased topo II alpha
      immunopositivity on patients' survival was also seen in the subgroup of patients
      with non-muscle invasive carcinomas (p = 0.0004), in patients with a bcl-2
      negative phenotype (p = 0.0330), and in those with low Ki-67 indices (p =
      0.0341). CONCLUSIONS: Because topo II alpha and Ki-67 failed to demonstrate a
      significant interrelation, they appear to be different molecules that both
      function at separate phases in the complex process of cellular proliferation. The
      assessment of increased topo II alpha immunoreactivity in specimens from
      urothelial carcinomas might help to select patients (particularly among those
      with superficial tumours) in the worse prognostic categories for new therapeutic
      strategies.

PMID- 11304850
TI  - Thyroglobulin immunoreactivity in lymph node histiocytes: a potential diagnostic
      pitfall.
AB  - AIMS: Strong thyroglobulin immunoreactivity within sinus histiocytes in a lymph
      node draining a papillary thyroid carcinoma was observed in a recent case. This
      prompted the investigation of whether thyroglobulin immunoreactivity is common in
      regional lymph nodes in cases of thyroid malignancy. METHODS: Eighty seven lymph
      nodes were studied from 21 cases of thyroid malignancy. These comprised papillary
      carcinoma (n = 12), follicular carcinoma (n = 4), medullary carcinoma (n = 3),
      and one case each of squamous and anaplastic carcinoma. Eleven cervical lymph
      nodes from patients with no evidence of thyroid disease were included as
      controls. Sections were stained with a monoclonal antibody against thyroglobulin.
      RESULTS: In the cases of thyroid malignancy, 32 of 87 lymph nodes showed positive
      staining for thyroglobulin of histiocytes within the subcapsular and medullary
      sinuses. In an additional four cases, there was positive staining of lymph within
      lymphatic channels. Positivity was present in at least one node in 15 of 21
      cases. There was no positivity in the control cases. There was no correlation
      between the size of the primary tumour and the presence of thyroglobulin
      positivity. CONCLUSIONS: Positive staining with antithyroglobulin occurs not
      uncommonly in sinus histiocytes in lymph nodes draining thyroid tumours. This
      positivity could be the result of the destruction of normal thyroid follicles,
      with the release of thyroglobulin, which is taken up by histiocytes, which
      subsequently drain to local lymph nodes. Pathologists should be aware of this
      phenomenon and should be careful not to interpret this as metastatic tumour.

PMID- 11304851
TI  - Should we screen for globin gene mutations in blood samples with mean corpuscular
      volume (MCV) greater than 80 fL in areas with a high prevalence of thalassaemia?
AB  - AIMS: To investigate whether it is worthwhile, in areas where thalassaemia is
      common, to screen for globin gene mutations in subjects with a mean corpuscular
      volume (MCV) above 80 fL, especially in partners of known thalassaemia carriers.
      METHODS: Blood samples from 95 subjects with MCV between 80 and 85 fL were
      screened for the presence of alpha globin gene mutations and the haemoglobin (Hb)
      E mutation. RESULTS: Thirty four subjects harboured globin gene mutations. Of
      these, 31 had deletions of one alpha globin gene, one had Hb Constant Spring, and
      three had Hb E mutations. CONCLUSION: Based on the above figures and known
      prevalence rates of thalassaemia carriers, it would seem worthwhile to screen for
      globin gene mutations in partners of known thalassaemia carriers, regardless of
      MCV, to identify pregnancies at risk of Hb H disease or Hb E/beta thalassaemia.

PMID- 11304852
TI  - Electron microscopy of myocardial tissue. A nine year review.
AB  - AIM: To review and reassess the role of this department's experience with routine
      electron microscopy of myocardial tissues. METHODS: A nine year series of
      myocardial samples that underwent electron microscopy analysis were audited.
      Fifty nine samples were derived from 46 male and 13 female subjects with an age
      range of 15-90 years (mean, 50.6). Forty two samples were endomyocardial
      specimens, with 13 being derived from explanted hearts, and four from necropsies.
      Two cases were from transplanted hearts. These were all reviewed in a blinded
      fashion, by all three authors separately, in terms of the myocardium at the
      ultrastructural level. Subsequently, the interpretations/diagnoses were cross
      compared with the light microscopy and clinical data results. [figure: see text]
      RESULTS: Four cases of amyloid were identified; in addition, one case of
      granulomatous inflammation and one case of basophilic degeneration were seen,
      although all these had been evident on light microscopy. One case of possible
      mitochondrial myopathy was found. A total of 18 cases revealed changes of a
      presumed non-specific type including glycogen, lipid, and mitochondrial
      accumulations. Varying types of degeneration involving myofibres were seen
      together with variations in interstitial fibrosis and occasional cytoplasmic
      inclusions. CONCLUSION: Overall, although interesting, the electron microscopy of
      myocardial tissue added little to the understanding of the patient's disease,
      with only one case showing changes not found at light microscopy or with other
      investigations. Further study might shed light on the "non-specific"
      ultrastructural findings encountered.

PMID- 11304853
TI  - Digital imaging of surgical specimens using a wet scanning technique.
AB  - AIM: To develop a simple method of recording digital images of surgical specimens
      on to a personal computer (PC) for use in presentations for teaching and
      reporting of their pathology. METHODS: A perspex box was constructed to
      international A4 size 100 mm deep. This box had a base of 3 mm clear perspex with
      sides and top of 5 mm white perspex. This box was partially filled with distilled
      water and a specimen immersed in it. It was then placed on top of a standard A4
      scanner. The specimen was then scanned into a PC using image capture software.
      RESULTS: The images produced showed noticeable improvement over normal
      photographs, especially with specimens prone to wet highlights. CONCLUSIONS: The
      method has proved to be a rapid and efficient means of producing macroscopic
      images of surgical specimens.

PMID- 11304854
TI  - Treatment of EBV driven lymphoproliferation with erythrophagocytosis: 12 year
      follow up.
AB  - This is a report of a case of Epstein-Barr virus (EBV) associated haemophagocytic
      syndrome in a 17 year old woman with antibody deficiency. For two years before
      this presentation, serology showed abnormally high titres to EBV early antigen,
      suggestive of persistent infection with EBV. She became acutely unwell with
      clinical features consistent with virus associated haemophagocytic syndrome
      (VAHS). Histology showed lymphoproliferation with erythrophagocytosis and
      evidence of EBV encoded RNAs in liver, spleen, and lymph node. VAHS is often
      fatal, particularly when it occurs in patients with underlying
      immunodeficiencies. In this case, treatment with intravenous immunoglobulin,
      aciclovir, and alpha interferon was followed by a dramatic recovery. Twelve years
      later the patient remains relatively well on regular intravenous immunoglobulin.

PMID- 11304855
TI  - Influence of smoking and alcohol on gastric chemokine mRNA expression in patients
      with Helicobacter pylori infection.
AB  - AIM: Chemokines that play a primary role in active inflammation are increased in
      gastric mucosa infected with Helicobacter pylori. Cigarette smoking increases the
      risk of peptic ulcer disease and gastric cancer, whereas alcohol might exert an
      antibacterial role. The aim of this study was to examine the association between
      smoking or alcohol consumption and mucosal chemokine mRNA expression in H pylori
      associated gastritis. METHODS: Gastric biopsy specimens were obtained from 46
      patients with dyspepsia who were infected with H pylori, and total RNA was
      extracted. Semiquantitative reverse transcription-polymerase chain reaction (RT
      PCR) was performed to quantify the mRNA expression of three C-X-C chemokines
      (interleukin 8 (IL-8), growth related oncogene alpha (GRO alpha), epithelial
      neutrophil activating protein 78 (ENA-78)) and two C-C chemokines (regulated on
      activation normal T cell expressed and secreted (RANTES) and monocyte chemotactic
      protein 1 (MCP-1)). RESULTS: GRO alpha and ENA-78 mRNA expression was
      significantly increased (p < 0.05) in 22 smokers compared with 24 non-smokers;
      however, no difference was seen in the expression of IL-8, RANTES, and MCP-1
      mRNA. No differences were observed in chemokine mRNA expression in relation to
      alcohol consumption. CONCLUSIONS: The increased C-X-C chemokine mRNA expression
      seen in smokers might play a role in inducing enhanced inflammatory activity in
      gastritis and the consequent severe diseases associated with H pylori infection.

PMID- 11304856
TI  - MPO-ANCA may produce a combination of P-ANCA and atypical cytoplasmic ANCA
      indirect immunofluorescent patterns on certain ethanol fixed neutrophil
      substrates.

PMID- 11304857
TI  - High prevalence of serum markers of coeliac disease in patients with chronic
      fatigue syndrome.

PMID- 11304858
TI  - Operative complications in HIV-infected women undergoing gynecologic surgery.
AB  - OBJECTIVE: To examine complications in HIV-positive women and controls undergoing
      gynecologic surgery and to evaluate the prognostic value of immune function for
      postoperative morbidity. STUDY DESIGN: A review of patients undergoing surgery by
      the gynecology faculty at the Johns Hopkins Medical Institutions from February
      1994 through November 1998 was performed. Fifty-three HIV-positive women were
      matched with 58 controls. Information on demographics, medical conditions,
      indication for surgery, surgery, blood loss, length of stay, perioperative
      hemoglobins, postoperative white blood cell counts and complications was
      collected. Data on HIV clinical stage, immune function and use of HIV medications
      were collected for HIV-positive patients. Odds ratio and chi 2 or two-sided t
      tests were used. Complication rates were also compared by CD4 counts and by HIV
      RNA levels. RESULTS: The only difference in demographics was by type of insurance
      (P < .001). Overall, 9 of 53 HIV-positive women had a complication as compared
      with 5 of 58 controls. There was no difference in the overall rate of
      complications or in specific complications, even when stratified by minor or
      major procedures. There were no differences between CD4 and HIV RNA groups for
      individual complications. CONCLUSION: The study found no differences in
      complications between HIV-positive and control patients and no association with
      immune status or viral load.

PMID- 11304859
TI  - Gynecologists' patterns of prescribing pessaries.
AB  - OBJECTIVE: To determine how gynecologists in the United States prescribe
      pessaries. STUDY DESIGN: A 34-question (long) survey was sent to 2,000
      gynecologists. Those who did not respond were then sent a five-question (short)
      survey. RESULTS: Nine hundred forty-seven (47.3%) long and short questionnaires
      were returned. Eighty-six percent of gynecologists prescribe pessaries. Most
      received minimal or no training in pessaries in their residencies. The most
      common pessaries used were the ring and doughnut. Uterine prolapse was treated
      most often with the Gellhorn and doughnut pessaries. The cube and Gellhorn
      pessaries were thought to be the most effective for vaginal vault prolapse. The
      Gehrung and ring pessaries were thought to be most effective for correction of
      cystocele. However, the ring pessary was considered the easiest to use. Follow-up
      visits were most often performed at one week, one month and then every three
      months. Estrogen was used in most cases. CONCLUSION: Most gynecologists prescribe
      pessaries. The ring pessary is used most often and is deemed the easiest to use.
      Pessaries are thought to work for all pelvic organ prolapse defects but are
      thought to be less effective for posterior defects. Follow-up of patients differs
      from manufacturers' recommendations.

PMID- 11304860
TI  - Vitamin B12 deficiency, infertility and recurrent fetal loss.
AB  - OBJECTIVE: To examine the relationship of infertility to recurrent fetal loss in
      patients who were vitamin B12 deficient. STUDY DESIGN: The obstetric histories of
      14 patients presenting with 15 episodes of vitamin B12 deficiency were analyzed.
      Infertility (two to eight years) had been present in four episodes, and recurrent
      fetal loss was a feature in 11. RESULTS: In six episodes, periods of recurrent
      fetal loss were followed by periods of infertility greater than one year.
      CONCLUSION: Hypercoagulability due to raised homocysteine levels may lead to
      fetal loss when vitamin B12 deficiency first develops. A more prolonged
      deficiency results in infertility by causing changes in ovulation or development
      of the ovum or changes leading to defective implantation.

PMID- 11304861
TI  - Hormone replacement therapy plus pelvic floor muscle exercise for postmenopausal
      stress incontinence. A randomized, controlled trial.
AB  - OBJECTIVE: To investigate the effects of the combination of pelvic floor muscle
      exercise (PFME) and estriol on postmenopausal stress incontinence (SI). STUDY
      DESIGN: Sixty-six patients with postmenopausal SI were randomized to a group
      treated with a combination of estriol (1 mg/d) and PFME (group A, n = 32) and a
      group treated with PFME alone (group B, n = 34). Efficacy was evaluated every
      three months based on stress scores obtained from a urinary incontinence (UI)
      questionnaire. RESULTS: A significant decrease in stress score was observed in
      mild and moderate UI patients in both groups three months after the commencement
      of therapy (A and B, P < .0001). The therapeutic effect in group A was more
      prominent for up to 18 months in mild UI and for up to 12 months in moderate UI
      (A vs. B, P < .05). Kaplan-Meier analysis showed that the cumulative morbidity
      rate in mild SI patients was significantly lower in group A (0%) than in group B
      (12%, P < .005). CONCLUSION: Combination therapy with estriol plus PFME was
      effective and is capable of serving as first-line treatment for mild SI.

PMID- 11304862
TI  - Soy isoflavone supplementation in postmenopausal women. Effects on plasma lipids,
      antioxidant enzyme activities and bone density.
AB  - OBJECTIVE: To investigate isoflavone supplementation on plasma lipids,
      erythrocyte antioxidant enzyme activities and bone mineral density in
      postmenopausal women. STUDY DESIGN: Thirty-seven postmenopausal women were given
      150 mg/d of isoflavone supplements twice daily for six months. Blood was sampled
      before and after supplementation, at three and six months. RESULTS: There were no
      significant differences in plasma total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, triglyceride concentrations or
      erythrocyte antioxidant enzyme activities after three and six months of
      supplementation when compared with the baseline. No significant changes were
      noted in calcaneus bone mineral density after supplementing isoflavones for six
      months. CONCLUSION: The antioxidant effect of isoflavones in normal
      postmenopausal women is not obvious, and supplementation with isoflavone alone
      may not have a hypocholesterolemic effect. Since the duration of this study was
      too short with respect to bone density, longer studies are needed to clarify the
      bone-sparing effect of isoflavone supplementation.

PMID- 11304863
TI  - Outcome of surgical treatment for superficial dyspareunia from vulvar
      vestibulitis.
AB  - OBJECTIVE: To evaluate the results of surgical treatment for superficial
      dyspareunia, as manifested by patient satisfaction, as well as epidemiologic
      characteristics of women with this medical problem. STUDY DESIGN: A questionnaire
      was sent to 69 women six months after the operation. It included questions about
      treatment before surgery and the impact of pain on the sexual relationship before
      and after the operation. Demographic, social and general health data were
      recorded before the operation. All patients returning the questionnaire were
      examined. RESULTS: Fifty-four (78%) patients replied. Half of those abstained
      from sexual relations before surgical treatment. Sixty-seven percent of patients
      required more than six visits to various physicians, before vestibulitis was
      diagnosed. Prior to surgery, 80% of patients received conservative treatment,
      whereas after surgery only 34% required it. A moderate to excellent improvement
      was reported after surgery by 45 (83%) patients. Repeat surgery (n = 7) resulted
      in further improvement in four patients. There were no major operative
      complications. Forty-five patients (83%) were satisfied with the results and
      would recommend the surgery to other women with this clinical problem.
      CONCLUSION: Surgical treatment for superficial dyspareunia from vestibulitis is
      quite safe and results in a high rate of patient satisfaction.

PMID- 11304864
TI  - Maternal serum tumor necrosis factor-alpha in patients with preterm labor.
AB  - OBJECTIVE: To evaluate maternal serum tumor necrosis factor-alpha (TNF alpha)
      levels in patients with preterm labor without clinical signs of chorioamnionitis
      and to compare these with levels in nonlaboring controls. STUDY DESIGN: The study
      group consisted of 44 patients with a singleton pregnancy admitted to our
      department with the diagnosis of preterm labor between 26 and 36 weeks'
      gestation. The control group consisted of 25 healthy consecutive patients with a
      singleton pregnancy without preterm contractions who were seen for routine
      antenatal visits. Maternal serum TNF alpha was measured using a solid-phase, two
      site chemiluminescent enzyme immunometric assay method, and levels were compared
      in patients with preterm labor and nonlaboring controls. RESULTS: The median
      maternal serum TNF alpha level for patients with preterm labor was 29.4 pg/mL
      (range, 12.3-173) as compared with 23 pg/mL (range, 11.9-62.7) in the control
      group (P = .031). Among 44 patients with preterm labor, 14 (32%) delivered within
      one week of admission. The median maternal serum TNF alpha level was
      significantly higher in patients who delivered within one week than in those who
      delivered after one week and controls (71.3 pg/mL [range, 28-173]) versus 22
      pg/mL (range, 12.3-86) versus 23 pg/mL (range, 11.9-62.7) (P < .0001).
      CONCLUSION: TNF alpha was elevated in patients with preterm labor, suggesting a
      role for maternal serum TNF alpha in its initiation.

PMID- 11304865
TI  - Chlamydia trachomatis and Pap testing from a single, fluid-based sample. A
      multicenter study.
AB  - OBJECTIVE: To determine the potential for both Pap testing and the Chlamydia
      direct fluorescence assay (DFA) from a single sample using the fluid-based
      ThinPrep Pap Test method (Cytyc Corporation, Boxborough, Massachusetts). STUDY
      DESIGN: Conventional DFA was compared to ThinPrep DFA in a direct-to-vial, double
      blinded, multicenter protocol. Cervical scrapings were collected for the ThinPrep
      Pap Test, and then a second swab was used to collect an endocervical sample for a
      conventional DFA test. The DFA slide prepared from the ThinPrep Test and the
      conventional DFA sample prepared from the endocervical swab were evaluated
      independently. Discrepant cases were adjudicated by testing residual specimens
      using a Chlamydia direct DNA method. RESULTS: Combining 636 adequate cases (94%
      of the total collected), 582 (91.5%) were negative on both slides, 43 (6.8%)
      positive by both and 11 (1.7%) discrepant. The prevalence of Chlamydia was 7.9%
      based on the conventional DFA method (range, 4.3-10.9%). McNemar's two-tailed
      test indicated the results not to be statistically different (P > .05).
      Adjudication favored ThinPrep 45% of the time and conventional 55%. Specimen
      adequacy favored ThinPrep with high statistical significance (McNemar's test, P >
      .01). CONCLUSION: A second slide prepared from the same vial of cells as that
      used for the ThinPrep Pap Test can be used for Chlamydia testing by DFA. Fluid
      based collection could allow multiple tests from a single sample.

PMID- 11304866
TI  - Voluntary screening program for HIV in pregnancy. Cost effectiveness.
AB  - OBJECTIVE: To determine the effectiveness of a voluntary human immunodeficiency
      virus (HIV) screening program in pregnancy. STUDY DESIGN: Using a business
      decision theory analysis model, we estimated the outcomes and costs of the two
      possible decisions by our patients (test/no test). Patients with a positive HIV
      screen would undergo evaluation and possible prophylactic antiviral therapy. The
      model was utilized to evaluate the Naval Medical Center San Diego Program from
      1995-1997. RESULTS: Prevalence of HIV in active duty Navy personnel during the
      years evaluated were 1995, 0.024%; 1996, 0.028%; and 1997, 0.022%. Patients
      screened for HIV during these years were 1995, 3,874; 1996, 3,924; and 1997,
      4,127 (n = 11,925). Incidence of HIV seroprevalence in patients screened during
      the study period was zero. The number of patients declining HIV screening was:
      1995, 10; 1996, 8; and 1997, 5. During the same period, reported HIV
      seroprevalence among pregnant patients in the United States was 1.5/1,000.
      CONCLUSION: HIV seroprevalence in our pregnant population (zero) was lower than
      expected, considering the national pregnancy prevalence and Navy prevalence. The
      expected number of cases of positive HIV screens was 17.8. The cost of the
      program for the study period was $103,748. The cost of care for one positive
      neonate ranges between $100,000 and $200,000.

PMID- 11304867
TI  - Pregnancy after intentional cryopreservation of percutaneous sperm aspiration
      specimens and intracytoplasmic sperm injection. A report of two cases.
AB  - BACKGROUND: Microsurgical epididymal sperm aspiration (MESA) and percutaneous
      epididymal sperm aspiration (PESA) are two methods of obtaining spermatozoa from
      patients with irreparable obstructive azoospermia. Intentionally using frozen
      thawed spermatozoa obtained from MESA had been reported to be successful. With
      minimal invasiveness, intentionally cryopreserved PESA specimens and
      intracytoplasmic sperm injection (ICSI) were carried out in two cases. CASES: Two
      cases of irreparable obstructive azoospermia received PESA, and the spermatozoa
      were cryopreserved intentionally. Successful ICSI was performed later, utilizing
      frozen-thawed spermatozoa. CONCLUSION: PESA and ICSI are promising methods for
      these patients. The major advantages are minimal invasiveness and flexibility for
      further treatment.

PMID- 11304868
TI  - Intramural leiomyoma during pregnancy becoming pedunculated postpartally. A case
      report.
AB  - BACKGROUND: The natural history of uterine leiomyomas during pregnancy has been
      reported. CASE: A 39-year-old primigravida presented with vaginal spotting in the
      10th week of pregnancy. Ultrasonic evaluation revealed a large intramural
      leiomyoma. Unsuccessful tocolysis at 25 weeks' gestation resulted in a cesarean
      section for breech presentation. At hysterotomy a 10-cm intramural leiomyoma was
      found in the right fundus and was left in situ. Six months later, at open
      laparotomy for myomectomy, the 10-cm leiomyoma was pedunculated, on a 4-cm stalk.
      CONCLUSION: Large intramural leiomyomas found at cesarean section may become
      pedunculated postpartally, thus making myomectomy easier and safer at a
      postpartum intervention than at the time of cesarean section. Also, prior
      knowledge of the possibility of myoma transformation from intramural to
      pedunculated postpartally may help in planning a later myomectomy. Myomectomy
      prior to pregnancy should be considered when it has caused a prior pregnancy
      complication.

PMID- 11304869
TI  - Persistent large choroid plexus cyst. A case report.
AB  - BACKGROUND: Prenatally diagnosed choroid plexus cysts regress or resolve
      spontaneously during pregnancy. A persistent large choroid plexus cyst with a
      prenatal diagnosis has not been reported previously. CASE: A 28-year-old, healthy
      primigravida was referred to our department at 32 weeks' gestation for a
      suspected fetal intracranial anomaly. Ultrasonography revealed a lateral
      ventricle 13 mm in width. The ventricle was dilated only in the atrium region.
      The choroid plexus was not distinct from the inner wall of the ventricle and did
      not fill the atrium of the lateral ventricle. The patient was followed with bi
      weekly ultrasonography until delivery, and the left ventricular width increased
      from 13 to 17 mm. At 38 weeks' gestation the patient delivered a 3,350-g girl.
      Magnetic resonance imaging showed a 1.7 x 2.5 x 3.0-cm cyst in the left lateral
      ventricle. Follow-up magnetic resonance imaging scans at 6 and 11 months showed
      unchanged findings. Clinical and neurologic examinations at 11 months of age
      showed normal development. CONCLUSION: Although small (< 1 cm), postnatally
      persistent choroid plexus cysts are clinically insignificant variants of normal;
      the prognosis of large, persistent cysts (> or = 1 cm) is less clear. Long-term
      neurologic follow-up is mandatory for these neonates.

PMID- 11304870
TI  - Metastatic placental site trophoblastic tumor. Report of a case with complete
      response to chemotherapy.
AB  - BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of
      gestational trophoblastic neoplasia, commonly insensitive to chemotherapeutic
      agents. CASE: We report on long-term remission in a patient with metastatic PSTT
      after etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine
      combination chemotherapy. The 27-year-old patient with metastatic lung PSTT was
      alive, without evidence of disease, > 40 months after treatment. CONCLUSION:
      Treatment with multiagent chemotherapy can produce long-term remission, even in
      patients with metastatic PSTT.

PMID- 11304871
TI  - Successful pregnancy outcome after preterm premature rupture of membranes at < 20
      weeks. A report of three cases.
AB  - BACKGROUND: Spontaneous preterm premature rupture of the membranes occurring
      before 20 weeks' gestation carries a perinatal mortality of approximately 82% and
      potential for considerable morbidity for mother and fetus. This is in contrast to
      amniotic fluid leakage after second-trimester amniocentesis, when the prognosis
      is usually good. CASES: We report three cases of spontaneous rupture of the
      membranes before 20 weeks' gestation, all associated with reaccumulation of
      amniotic fluid and satisfactory neonatal outcomes. CONCLUSION: Our cases may
      represent a subgroup with a relatively good prognosis. The existence of such
      subgroups would better be determined in a prospective, cohort study, and it might
      need to be a multicenter one. It requires well-defined entry criteria, management
      protocols and neonatal follow-up as well as information about pregnancies where
      termination, rather than continuation, is chosen.

PMID- 11304872
TI  - Cerebellar metastasis from papillary serous adenocarcinoma of the ovary mimicking
      Meniere's disease. A case report.
AB  - BACKGROUND: In rare cases, cerebellar metastasis originating in serous papillary
      adenocarcinoma of the ovary can mimick Meniere's disease. CASE: A 51-year-old
      woman, with complete remission after optimal maximal debulking and chemotherapy
      for an International Federation of Gynecology and Obstetrics IIIc primary ovarian
      carcinoma, presented with nausea, vomiting, vertigo and headache 18 months after
      surgery. Investigations revealed a solitary cerebellar cystic mass, 4.6 x 4.0 x
      3.2 cm. Gross total excision of the cerebellar lesion followed by brain
      irradiation resulted in complete resolution of her symptoms. Histology showed a
      metastatic tumor consistent with the primary ovarian carcinoma. CONCLUSION: In an
      atypical presentation in patients with metastatic ovarian carcinoma, thorough
      investigations should be done to rule out or confirm brain metastasis, which can
      be aggressively managed to prevent serious consequences and improve outcome.

PMID- 11304873
TI  - Molar pregnancy with a coexistent fetus after intracytoplasmic sperm injection. A
      case report.
AB  - BACKGROUND: Normal fertilization is usually considered to have occurred when two
      pronculei (2PN) and two polar bodies are observed. Exceptions are the single
      pronucleated zygote resulting from asynchronous pronuclei. CASE: A 29-year-old
      woman entered a program of intracytoplasmic sperm injection and embryo transfer
      because of her husband's oligoasthenoteratozoospermia. Two cleavage-stage embryos
      (four blastomeres, grade 1 and 2) were obtained from one fertilized oocyte
      containing distinct 2PN and the other a single pronucleus (1PN). At 15 weeks'
      gestation the patient developed severe preeclampsia requiring termination of the
      pregnancy. Histopathologic examination and DNA ploidy by image analysis were
      consistent with a twin pregnancy combining a complete hydatidiform mole and
      normal pregnancy. CONCLUSION: We hypothesize that this 1PN was at the origin of
      the hydatidiform mole. This case highlights the danger of transferring an embryo
      having 1PN.

PMID- 11304874
TI  - Vaginal delivery of monoamniotic twins with umbilical cord entanglement. A case
      report.
AB  - BACKGROUND: Monoamniotic twinning is frequently complicated by umbilical cord
      entanglement and fetal death. Should vaginal delivery take place, this may
      present as an acute intrapartum emergency. CASE: A 26-year-old woman, gravida 3,
      para 2, presented in the second stage of labor and gave birth to a macerated,
      stillborn infant weighing 1,340 g. At the time of delivery it was not known that
      this was a twin pregnancy. Delivery was achieved only after division of a cord
      around the neck; it turned out to be that of a live, second twin. This infant,
      weighing 2,530 g, was delivered by rapid breech extraction and made a
      satisfactory recovery. CONCLUSION: When multiple pregnancy or monoamniotic
      multiple pregnancy has not been excluded, a nuchal cord might be that of an
      undiagnosed second twin.

PMID- 11304875
TI  - Leiomyosarcoma after uterine artery embolization. A case report.
AB  - BACKGROUND: Hysterectomy is the most common treatment for relieving symptoms
      attributable to uterine leiomyomas; however, alternatives to hysterectomy are
      becoming increasingly available. Uterine artery embolization is being used more
      frequently in this clinical setting. CASE: A leiomyosarcoma was diagnosed
      incidentally in a 51-year-old, nulliparous woman who underwent uterine artery
      embolization for symptomatic leiomyomata and subsequent total abdominal
      hysterectomy/bilateral salpingo-oophorectomy due to unsatisfactory results of the
      embolization procedure. CONCLUSION: While the occurrence of preoperatively
      undiagnosed uterine leiomyosarcomas among patients undergoing hysterectomies has
      been reported, there are no reports of unsuspected leiomyosarcomas after uterine
      artery embolization. Criteria for selection of patients for the procedure should
      consider the possibility of leiomyosarcoma. With the increasing popularity of
      uterine artery embolization, cases like this are likely to be encountered in the
      future.

PMID- 11304876
TI  - Safety of estrogen/androgen regimens.
AB  - A persistent view of testosterone as the "male hormone" deprives many clinically
      androgen deficient women of effective treatment, although data from the 1960s to
      the present have indicted the importance of androgens to libido and feelings of
      well-being in women, providing relief from vasomotor symptoms that are
      unresponsive to estrogen alone. The safety of androgen replacement therapy is
      reviewed in this article. The risk of androgen toxicity is influenced by dosage
      and route of administration. Most products developed for use in men produce
      androgen levels that are too high for safety in women. Low-dose androgen
      replacement therapy as used in women, 1.25 mg esterified estrogen (EE) + 2.5 mg
      methyltestosterone (MT), or a half-strength preparation, 0.625 mg EE plus 1.25 mg
      MT, is unlikely to produce commonly described side effects: liver dysfunction,
      adverse lipid effects or virilization, as reviewed in this article. The potential
      for adverse endometrial effects if used by women with uteri unless a progestogen
      is used is also discussed. Low-dose estrogen/androgen therapy offers beneficial
      cardiovascular effects, primarily regarding lipids, atherogenesis and
      vasodilation. Androgens may act independently on the cardiovascular system and
      may be mediated by estrogen metabolites (aromatization products) or by secondary
      effects of androgens on estrogen bioavailability and metabolism (sex hormone
      binding globulin [SHBG] effects). They may improve vasomotor stability and reduce
      triglyceride (TG) levels. The marked reduction in TG in the estrogen/androgen
      (E/A) regimen is of note because women who experience oophorectomy have
      significantly increased levels of TG as compared with women who are naturally
      menopausal. Androgens offer positive effects on bone. Various types of studies-
      including cell culture, preclinical and observational--have attempted to document
      potential associations between androgens and breast cancer. Androgen
      administration has been shown to induce down-regulation of mammary epithelial
      proliferation and estrogen receptor expression, suggesting that E/A therapy might
      reduce the risk of breast cancer associated with ERT. However, studies of the
      relation of breast cancer to elevated circulating androgen levels have yielded
      inconsistent results. Testosterone may have an indirect effect on breast cancer
      risk because of its association with estrogen levels. Testosterone's effect on
      estrogen bioavailability may be of importance since an increase in serum
      testosterone levels could lead to a decrease in the percent of estradiol bound to
      SHBG. For the surgically menopausal woman faced with significant symptoms and
      health risks associated with estrogen withdrawal, E/A supplementation offers a
      reasonable course of treatment.

PMID- 11304877
TI  - Testosterone deficiency in women.
AB  - Testosterone (T) is an important component of female sexuality, enhancing
      interest in initiating sexual activity and response to sexual stimulation.
      Testosterone is also associated with greater well-being and with reduced anxiety
      and depression. Clinical and biochemical definitions of T deficiency have not
      been established; hence, the prevalence of this condition is not known. However,
      surgically menopausal women are among the populations most likely to experience T
      deficiency, a syndrome characterized by blunted or diminished motivation;
      persistent fatigue; decreased sense of personal well-being; sufficient plasma
      estrogen levels; and low circulating bioavailable T (either a low total T/sex
      hormone binding globulin (SHBG) ratio or free T in the lower one-third of the
      female reproductive range); and low libido. Exogenous estrogen, particularly when
      administered orally, increases SHBG, which, in turn, reduces free T and estradiol
      (E2). After oophorectomy, levels of T and its precursor, androstenedione, decline
      by approximately 50%. T replacement continues to be evaluated as an adjunct to
      estrogen replacement therapy, particularly for women with androgen deficiency
      symptoms, surgically menopausal women and women with premature ovarian failure.
      In the United States, oral methyltestosterone is the common product currently
      approved for androgen replacement in women. The best product specifically
      designed for women has yet to be determined, as standardized, long-term,
      randomized, control clinical studies are lacking and product refinement
      continues.

PMID- 11304878
TI  - Issues surrounding surgical menopause. Indications and procedures.
AB  - More than 25% of women in the United States undergo hysterectomy by age 60. In
      assessing the appropriateness of this procedure, physicians should consider the
      surgical techniques available, the impact of ovary removal and the subsequent
      induction of menopause, and the requirement of long-term estrogen replacement.
      The option of ovarian preservation should also be explored. When ovaries are
      healthy and viable, without malignancy, preservation may be possible to ensure
      that the maximum natural hormonal benefits can be gained by the patient, thus
      avoiding the immediate and sharp decline in hormone production created by
      surgical menopause. The long-term effects of loss of ovarian function--including
      impact on cardiovascular and bone health and the immediate vasomotor symptoms and
      urogenital impact--are also problematic. The loss of androgens and estrogen, the
      physical and psychologic implications, and the requirement of compliance with a
      hormone replacement regimen over a longer period of time should be balanced
      carefully. In the gynecologic profession, no consensus exists concerning the
      optimum method by which to perform a hysterectomy in different situations. The
      method selected depends more on the experience and biases of the surgeon than on
      a critical evaluation of operative and outcome data. This paper reviews
      indications for hysterectomy, the advantages and disadvantages of various
      procedures, and the circumstances in which ovarian preservation is warranted.
      Options and various procedures are discussed for treating such conditions as
      pelvic inflammatory disease and tuboovarian abscess, chronic pelvic pain, cancer
      and residual ovary syndrome. Also discussed is the impact of various procedures
      on patient well-being, cost, complications and the need for additional surgery.

PMID- 11304879
TI  - Psychological consequences of surgical menopause.
AB  - More than 250,000 women have a bilateral oophorectomy every year. With surgical
      menopause, the onset of menopausal symptoms is abrupt and often dramatic.
      Oophorectomy offers relief from physical conditions for many women; however,
      those with preexisting psychological and some physical problems tend to
      experience postsurgical exacerbation of those problems. Loss of estrogenic and
      androgenic underpinnings may destabilize women with unstable psychiatric axes.
      Surgically menopausal women may also experience a decline in sexual interest and
      activity. The relation of surgical menopause to physiologic and sexual well-being
      is described in this article. The link between hormonal levels and psychological
      well-being has been well documented. Depression seems to be increased at times of
      changing hormone levels in women, possibly a result of the effect of estrogen
      levels on serotonergic activity and its impact on other neurotransmitters. In
      addition, a sex-specific association with specific psychological disorders has
      been described in the literature and will be reviewed in this article. The
      potential benefits of estrogen or estrogen/androgen therapy on libido and mood
      are discussed, as are findings that estrogen-androgen therapy correlated with
      less anxiety and hostility and with increased positive feelings when compared
      with estrogen-only treatment.

PMID- 11304880
TI  - Effects of estrogen/androgen therapy on bone mineral density parameters.
AB  - Although estrogen's efficacy in reversing loss of bone mineral density (BMD) has
      been extensively documented, the role of androgens in preserving and restoring
      BMD is less well understood. Estrogen/androgen (E/A) therapy is especially
      important for surgically menopausal women. This population group experiences
      marked bone loss in response to the dramatic decline in ovarian hormones. The
      resulting hormonal profile differs significantly from that of naturally
      menopausal women. For surgically menopausal women, the relation of estrogens,
      androgens and sex hormone binding globulin (SHBG) is of special concern, as the
      interrelation between these hormones ultimately may reduce hormonal
      bioavailability. This paper reviews the relation of bone metabolism to ovarian
      hormones and the mechanics of BMD loss as well as the tools available to
      clinicians to assess bone loss in menopausal women. It further discusses androgen
      excess in women with polycystic ovary syndrome. Currently available hormonal
      regimens to preserve bone are described, including estrogen-only therapy, E/A
      therapy, tibolone and estrogen-progestogen therapy.

PMID- 11304881
TI  - [Psychiatry online--one-year experience from the practice of virtual psychiatry].
AB  - Nowadays people very often seek health information on the Internet. They use
      electronic mail, mailing and news groups as well as web services. Internet allows
      to acquire quick answers to almost all questions. It can be anonymous. The use of
      Internet is fairly cheap. The answer of each Internet question causes ethical and
      the moral problems. An expert has no direct contact with an ill person. He does
      not know if the person who asked is ill or wants to receive information about
      someone else. People ask about diseases which they or their families suffer from.
      They ask about drugs they take or they will take, about side-effects,
      interactions and prices. Some questions are asked by students, doctors and other
      people who are interested in psychiatry. Internet is an enormous place, where
      patients and doctors search for and obtain information.

PMID- 11304882
TI  - [A case of a case of mild cognitive impairment--diagnostic uncertainties].
AB  - In the paper a case of mild cognitive impairment is presented. It is interesting
      because of its atypical psychopathological picture. The primary disorder is
      accompanied with symptoms of depression and anxiety. A course of diagnosis and
      treatment are outlined.

PMID- 11304883
TI  - [Evaluation of prevalence of emotional low self esteem and neurosis in Poland in
      1996].
AB  - The paper presents psychiatric problems included in national, health interview
      survey, recommended by the WHO, carried out by the Central Statistical Office in
      Poland in 1996. Authors are going to estimate the prevalence of a bad frame of
      mind and neurosis among Polish adult people and try to appoint the relationships
      between psychiatric disorders and gender and place of residence. We estimated
      results in 49 provinces. There were significant differences between east and west
      Poland. People who live in eastern provinces have a worse psychological condition
      than western. Women have higher rate of these this psychiatric problems. We also
      found a major correlation between dissemination of a bad frame of mind and
      neurosis among men and women.

PMID- 11304884
TI  - [Evaluation of reliability and validity of Insight into Illness Scales].
AB  - In the present study basic psychometric properties of Insight into Illness Scale
      (IIS) were evaluated. 25 hospitalized patients with a diagnosis of paranoid
      schizophrenia confirmed by criteria of ICD-10 were examined. Indices of
      reliability (internal consistency, interrater reliability, retest reliability)
      and validity (intercorrelations of insight instruments) were assessed. The
      obtained data suggests that the IIS is a reliable and valid tool for assessment
      of insight.

PMID- 11304885
TI  - [Scales of the "O" symptom questionnaire].
AB  - The article presents the scales of the "O" Symptom Check-list which were derived
      on the basis of an analysis of a patient population of over three thousand. The
      patients filled out the "O" Symptom Check-list before treatment. 14 variables of
      various syndromes were constructed, which corresponded with most of the neurotic
      disorders classified in ICD-10. The results obtained were compared with the
      scales constructed 20 years ago, in an attempt to explain the dynamics of the
      psychopathology in the course of those years. It was noted that the analysis of
      the results of the single scales can be helpful in defining and observing the
      most common neurotic disorders and noting their comorbidity.

PMID- 11304886
TI  - [S-II symptom questionnaire].
AB  - "S-II" Symptom Check-list which allows for a fast diagnosis of neurotic
      disorders. A result of 165 points suggests the incidence of such disorders with
      the probability of 90%. The methodology of the construction of the check-list
      intends for the application of questions most common in those ill due to neurotic
      disorders (owing to the change in frequency) and the most possibly equal amount
      of questions on the symptoms common to women and men. Thanks to this the norm for
      women and men is identical. SCL S-II Symptom Check-list is a shortened and
      actualised version of the "O" Symptom Check-list, developed in 1975. It is
      similar to the SCL-90 and highly correlated with it, but it does not contain the
      variables concerning the psychotic symptoms. Thanks to this, its' accuracy
      (specificity) in the diagnosis of neurotic disorders is high. 4 pairs of
      questions allow for the judgement of answer reliability. 10 scales were singled
      out in the questionnaire. They are only of a helpful value and do not allow for a
      one-sided diagnosis of the type of the disorder, listed in the ICD-10. The scale
      results can, however make the correct diagnosis easier.

PMID- 11304887
TI  - [The effect of attention on rotations of drawings in the Bender test].
AB  - The aim of the work was to prove the dependence of middle degree rotations of the
      drawings in Bender test and its form on attention level defined in digit span
      test (part I--repeated directly). The material consisted of 40 patients treated
      in Neurological Clinic of Medical University in Wroclaw (24 of them had organic
      brain disorder, 16--had not any brain disease). In statistical analysis I used
      the Kruskal-Wallis non-parametric method and parametric simple regression
      analyses. I proved that the dependence was of curve-lined character and was
      expressed by the formula: ln Y = 3,26181 - 1,08144 ln X. This equation explains
      9% variability in middle rotation degrees obtained in examination.

PMID- 11304888
TI  - [Anxiety and depression in post-traumatic disorders].
AB  - The paper presents the research results of those who had PTSD and were examined.
      The group was of 90 persons, who were former political prisoners in Poland. The
      State and Trait of Anxiety Inventory and the Hamilton Depression Rating Scale
      were applied in order to measure the intensity of anxiety and depressive
      symptoms. 76% of those examined had nightmares. This group is also significant
      for its' high level momentary anxiety, anxiety as a persistent personality trait
      as well as uncommon (20%) incidence of depression. The group of those that do not
      remember nightmares (24% of all those examined) is characterised by a lower level
      of anxiety reaction and common incidence of depression (84.2%). The article is
      ended with a discussion on the meaning of the results for the diagnosis and
      treatment of post-traumatic disorders.

PMID- 11304889
TI  - [Pharmacotherapy for depression in patients with myocardial ischemia].
AB  - The comorbidity of depression and heart diseases is an important but still
      devaluated clinical problem. Mood disorders in those ill with cardiac ischaemic
      disease significantly worsen the predictive mortality and quality of life. It may
      be predicted that adequate therapy of depression could have a positive effect on
      the long term course of IHD. Careful analysis of indications and contradictions
      as well as the application of new generation drugs allows for safe therapy.
      Evident benefits of appropriate treatment of depression in this group of
      patients, deny the old thesis on the damage of antidepressive drugs on the cardio
      vascular system.

PMID- 11304890
TI  - [New diagnostic criteria for the neuropsychiatric form of systemic lupus
      erythematosus].
AB  - Systemic lupus erythematosus (SLE) is an autoimmunologic illness, which apart
      from changes in the skin, the locomotor system and the internal organs, attacks
      also the nervous system. The paper presents 19 neuropsychiatric symptomic
      syndromes which after conduction of multidisciplinary, international research
      were accepted by the American College of Rheumatology (ACR) as the criteria of
      systemic lupus erythematosus (SLE). This broadens the criteria applied since
      1982, which were only considering acute symptoms and psychoses as characteristic
      of the neuropsychiatric form of systemic lupus erythematosus (NPSLE). In the new
      neurologic criteria concerning the CNS are: epileptic attacks and acute attack
      disorders, headaches, vascular diseases, demyelinating syndrome, aseptical
      meningitis, chorea, myelopathy. Psychiatric syndromes which make up the new
      criteria are: acute amentive state, anxiety disorders, cognitive function
      impairment, affective disorders, psychoses. The criteria connected to the CNS
      are: cranial nerve damage, mononeuropathy, damage of nerve plexus,
      polyneuropathy, vegetative neuropathy, myasthenia and acute inflammatory
      demyelinating polyneuropathy. Clinical symptoms of these syndromes were set and
      laboratory and visualising tests were developed, which are useful in their
      diagnosis. The intention of the ACR in setting new, significantly broader
      criteria of NPSLE, was to stress the diversity of symptoms and for a practical
      aspect to allow the diagnosis of NPSLE in patients having this disease, in whom
      the symptoms connected with the nervous system may dominate in the clinical
      picture, or may be before the dermatological, locomotor or internal organ
      symptoms.

PMID- 11304891
TI  - Prevention of a first myocardial infarction.
AB  - Coronary heart disease is the leading cause of morbidity and mortality in men and
      women in the Western world. We now have significant evidence that prevention of
      the first coronary event using lifestyle and pharmacologic therapies is
      paramount. Events are caused by inflamed arteries leading to rupture of
      atherosclerotic plaques that induce potentially occlusive thrombi. Analysis of
      event reduction trials has revealed that LDL-C lowering is only one part of the
      therapy needed to stabilize plaque. HMG-Co-A-reductase inhibitors, fibrates, and
      statins all have differing mechanisms of action that provide not only lipid but
      also inflammatory, rheologic, and coagulation benefits. Concentration and sizes
      of lipoprotein subfractions have emerged as important new tools with small dense
      LDL particles having more atherogenicity, which has led to an increasing use of
      aggressive combination therapy for prevention of first myocardial infarction.
      Proper use of lipid-lowering therapies requires knowledge of drug metabolism drug
      drug interactions.

PMID- 11304892
TI  - Use of in vitro drug metabolism data to evaluate metabolic drug-drug interactions
      in man: the need for quantitative databases.
AB  - It has become widely accepted that metabolic drug-drug interactions can be
      forecast using in vitro cytochrome P450 (CYP) data. For any CYP form-inhibitor
      pair, the magnitude of the interaction will depend on the potency of the
      inhibitor (inhibition constant, Ki) the concentration of the inhibitor available
      for inhibition ([I]), the fraction of the substrate dose metabolized by CYP (fm),
      and the fraction of the CYP-dependent metabolism catalyzed by the inhibited CYP
      form (e.g., fm,CYP3A4). While progress is being made toward our understanding of
      the factors necessary for predictions of [I]/Ki in vivo, it is evident that there
      is a need for quantitative databases that contain in vitro (e.g., Ki, fm,CYP3A4)
      and in vivo pharmacokinetic/absorption-distribution-metabolism-excretion
      (PK/ADME) data (e.g., fm) for a large number of marketed drugs. Ultimately, such
      databases would allow one to integrate all of the data necessary for the
      prediction of drug-drug interactions and permit the rational evaluation of new
      drug entities.

PMID- 11304893
TI  - A dose-ranging study of gentamicin pharmacokinetics: implications for extended
      interval aminoglycoside therapy.
AB  - Prolonged distribution time has been noted for high-dose (7 mg/kg) gentamicin.
      Higher doses are used for extended-interval aminoglycoside therapy (EIA). The
      authors investigated whether the increase in distribution time was proportional
      to the dose of gentamicin. Twelve healthy volunteers were given low (LD, 2
      mg/kg), medium (MD, 4.5 mg/kg), and high (HD, 7 mg/kg) doses of gentamicin in a
      randomized, crossover fashion. Gentamicin was infused over 30 minutes, with 15
      concentrations obtained over 8 hours after each dose. Data were fit to a two
      compartment pharmacokinetic model. Distribution half-life for HD (31.1 +/- 5.7
      min) differed significantly (p < 0.05) from LD (22.4 +/- 6.1 min) and MD (23.8 +/
      5.1 min) with no significant difference being seen between LD and MD. This study
      verifies that when using EIA dosing with HD gentamicin, sampling within 90
      minutes after the beginning of the infusion provides information that leads to
      overestimation of peak serum concentration/minimum inhibitory concentration and
      inaccurate calculation of pharmacokinetic parameters.

PMID- 11304894
TI  - Pharmacokinetics and pharmacodynamics of recombinant FGF-2 in a phase I trial in
      coronary artery disease.
AB  - Fibroblast growth factor-2 (FGF-2) is a heparin-binding protein capable of
      inducing angiogenesis in multiple animal models of chronic ischemia. The
      pharmacokinetics and pharmacodynamics of a single dose of recombinant FGF-2 (rFGF
      2) administered by intracoronary or intravenous infusion were evaluated in a
      Phase I trial in 66 patients with severe coronary artery disease. rFGF-2
      displayed biphasic elimination with a mean studywide distribution t1/2 of 21
      minutes and a mean apparent terminal elimination t1/2 of 7.6 hours. Systemic
      exposure to rFGF-2 was comparable following intracoronary or intravenous
      administration. Peak plasma concentration and area under the concentration-time
      curve increased proportionally with dose, indicating linear pharmacokinetics over
      the dose range examined (0.33 to 48.0 micrograms/kg). Greater systemic exposure
      was observed when heparin was administered closer to rFGF-2 infusion, consistent
      with slower clearance of heparin/rFGF-2 complexes. Infusion of rFGF-2 was
      associated with changes in acute hemodynamics. While a clear PK/PD dose-response
      relationship was not established, a trend toward hypotension and tachycardia with
      higher rFGF-2 doses was observed.

PMID- 11304895
TI  - Metabolic disposition and pharmacokinetics of [14C]-amprenavir, a human
      immunodeficiency virus type 1 (HIV-1) protease inhibitor, administered as a
      single oral dose to healthy male subjects.
AB  - The objective of this study was to determine the metabolic profile, routes of
      elimination, and total recovery of amprenavir and its metabolites after a single
      oral dose of [14C]-amprenavir. Six healthy male subjects each received a single
      oral 630 mg dose of amprenavir containing 95.76 microCi of [14C]-amprenavir in
      this Phase I mass balance study. The metabolic disposition of amprenavir was
      determined through analyses of radiocarbon in whole blood, plasma, urine, and
      stool samples, collected for a period of 10 to 17 days postdosing. Cerebral
      spinal fluid (CSF) sampling was conducted on day 1. The ratio of unchanged
      amprenavir AUC0-->infinity to plasma radiocarbon was 27%, suggesting that most of
      the radiocarbon was metabolites. The median total recovery of the administered
      dose of radiocarbon was 89% (range: 66%-93%), with 75% (range: 56%-80%) recovered
      in the feces and 14% (range: 10%-17%) in the urine. Most of the recovered
      radiocarbon in the feces and urine was excreted within 240 and 48 hours postdose,
      respectively. Of the 75% of the radiocarbon dose recovered in the feces, 62% was
      identified as a metabolite resulting from dioxidation of the tetrahydrofuran ring
      (GW549445X) and 32% as a metabolite resulting from subsequent oxidation of the p
      aniline sulfonate group (GW549444X). Unchanged amprenavir was below the limit of
      quantitation in feces and urine. Therefore, approximately 94% of the dose
      excreted in the feces was accounted for by these two metabolites. Concentrations
      of radiocarbon in the CSF were below the limit of quantitation in 5 of 6 subjects
      sampled. In summary, oral amprenavir is extensively metabolized in humans, with
      concentrations of unchanged drug below the limits of quantitation in urine and
      feces. The majority (75%) of administered radiocarbon was excreted in feces.

PMID- 11304896
TI  - Single-dose pharmacokinetics of atrasentan, an endothelin-A receptor antagonist.
AB  - The pharmacokinetics of 1, 10, 23.25, and 139.5 mg doses of atrasentan was
      assessed in a placebo-controlled, double-blind, single oral dose study in 24
      healthy male subjects. Atrasentan was well tolerated. Atrasentan pharmacokinetics
      was linear in the 1 to 23.25 mg dose range, with some dose dependency in the
      highest dose group. Harmonic mean terminal half-life was similar across all dose
      groups (20-25 h). Apparent oral clearance was low (12 L/h) for the highest dose
      group compared with the other three dose groups (21-27 L/h). The apparent volume
      of distribution was large (approximately 6 L/kg), consistent with extensive
      tissue distribution.

PMID- 11304897
TI  - Multiple-dose pharmacokinetics and safety of two regimens of
      quinupristin/dalfopristin (Synercid) in healthy volunteers.
AB  - Quinupristin/dalfopristin (Q/D) is a novel streptogramin antibiotic for the
      treatment of severe gram-positive infections. The purpose of this open,
      nonrandomized, parallel-group, phase I trial was to evaluate Q/D pharmacokinetics
      after single and repeated doses under the two different dosing regimens
      corresponding to the effective doses and to evaluate tolerability. Two groups of
      10 healthy volunteers received multiple 1-hour intravenous infusions of 7.5 mg/kg
      Q/D either every 8 or 12 hours for 4 or 5 days, respectively. Plasma
      concentrations of Q, D, and metabolites were determined using high-performance
      liquid chromatography and selective microbiological assays. The two regimens q8h
      and q12h lead to the same disposition profile after single and repeated
      administration. Single-dose data confirmed the high plasma clearances of Q and D
      (about 0.90 l/h/kg) obtained previously. Unchanged drugs were the main components
      in plasma, with each of the three metabolites representing about 20% (in terms of
      the AUC ratio) of the parent drugs. Comparable steady-state concentrations were
      reached from day 2 of both regimens. A similar moderate increase in Cmax and AUC
      (about 20%) of parent drugs was observed between the first and last day of
      treatment. This phenomenon, which was also observed for the metabolites, was not
      expected considering the short terminal disposition half-lives of the parent
      drugs and trough plasma concentrations of all components mostly below the limits
      of quantitation at steady state, whatever the dosing regimen. The clearances of
      parent drugs at steady state were about 20% lower as compared with that observed
      following the first drug administration (statistically significant difference).
      No trend suggesting a treatment effect on any laboratory parameter, vital signs,
      or electrocardiographic parameters was identified. However, 80% of subjects
      reported venous adverse events probably related to treatment.

PMID- 11304899
TI  - Pharmacokinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate
      (DS) after intravenous and intramuscular administration: a comparison with
      dexamethasone phosphate (DP).
AB  - The pharmacokinetics (PK) and pharmacodynamics (effects on blood lymphocytes) of
      dexamethasone (D) after intravenous (i.v.) administration of dexamethasone
      phosphate (DP, 10 mg, equivalent to 8.3 mg of dexamethasone) and after
      intravenous and intramuscular (i.m.) administration of dexamethasone
      sulfobenzoate sodium (DS, 9.15 mg, equivalent to 6 mg of dexamethasone) were
      assessed. Only 25% of DS was converted into dexamethasone with a half-life for DS
      of 5.4 hours and 7.4 hours after i.v. and i.m. administration, respectively.
      Consequently, the mean residence time of D after both i.m. and i.v.
      administration of DS (10.4-11.6 h) was longer than that after DP administration
      (6.1 h). The smaller lymphocyte suppression induced by DS (50% of that after DP
      administration) was shown to be related to differences in the pharmacokinetics.
      This study revealed significant differences in the pharmacokinetics of D after
      administration of DS and DP and stresses the importance of the prodrug for the
      pharmacological response. Because of the slow and incomplete conversion of DS
      into dexamethasone, its use in emergency medicine situations should be critically
      evaluated.

PMID- 11304898
TI  - Time-variant increase in methylprednisolone clearance in patients with acute
      respiratory distress syndrome: a population pharmacokinetic study.
AB  - Methylprednisolone (MP) disposition was evaluated in 20 individuals who
      participated in an ongoing randomized, double-blind, placebo-controlled study
      designed to evaluate the efficacy of MP in the treatment of acute respiratory
      distress syndrome (ARDS). MP (1 mg/kg) was given as a loading infusion over 30
      minutes followed by a 1 mg/kg/day continuous i.v. infusion. Patients were
      switched to oral MP upon restoration of oral intake. MP plasma concentrations (n
      = 110) were determined using a specific HPLC method. Population pharmacokinetic
      analysis was performed using nonlinear mixed-effects models, implemented in
      NONMEM, version V. MP plasma concentration data were described by a one
      compartment open model with a time-dependent, non-linear increase in the
      clearance (CL) of MP during the course of therapy. Initial clearance of MP (CLo)
      in ARDS patients at the start of therapy increased to a maximal value (CLmax)
      after approximately 7 days. The estimate of CLmax was similar to the CL of MP in
      healthy individuals reported previously. Population mean estimates (+/- SE) of
      parameters in the model were as follows: CLo = 13.2 +/- 2.4 L/h, CLmax = 25.0 +/-
      3.6 L/h, time of half-maximal increase in CL (T50) = 41.1 +/- 8.2 h, gamma (Hill
      coefficient) = 3.8 +/- 0.6, and volume of distribution (Vd) = 137 +/- 30.2 L.
      Disease progression indices and patient demographics were evaluated as
      covariates, and no significant correlation was found. Means (+/- SD) of plasma
      protein binding differed between healthy individuals (72% +/- 4%) and ARDS
      patients (46% +/- 11%) (p < 0.001). The pharmacokinetics of MP in ARDS patients
      has not been described previously.

PMID- 11304900
TI  - Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV
      positive subjects.
AB  - The objective of this study was to determine the effects of double-strength
      grapefruit juice on gastric pH and systemic bioavailability of indinavir in HIV
      infected subjects receiving indinavir. Fourteen HIV-infected subjects took 800 mg
      of indinavir with 6 ounces (180 ml) of water or double-strength grapefruit juice.
      Gastric pH was measured and blood samples were collected for 5 hours after
      indinavir dosing. Grapefruit juice increased the mean gastric pH (from 1.39 +/-
      0.4 to 3.20 +/- 0.3; p < 0.05) and slightly delayed the absorption of indinavir
      (tmax increased from 1.12 +/- 0.8 h to 1.56 +/- 0.6 h; p < 0.05). However, there
      were no significant differences in indinavir exposure. Cmax was 16.7 +/- 7.3
      microM with water versus 13.9 +/- 4.2 microM with grapefruit juice (p = NS), and
      AUC0-8 was 37.5 +/- 19 with water versus 36.9 +/- 15 with grapefruit juice (p =
      NS). The authors concluded that concomitant administration of grapefruit juice
      increases gastric pH and delays indinavir absorption but does not uniformly
      affect the systemic bioavailability of indinavir in HIV-infected subjects.

PMID- 11304901
TI  - Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a
      CYP2D6 probe.
AB  - Two antidepressants, venlafaxine and fluoxetine, were evaluated in vivo for their
      effect on cytochrome P450 2D6 (CYP2D6) activity, measured by the ratio of
      dextromethorphan, a sensitive CYP2D6 marker, to its metabolite dextrorphan (i.e.,
      DM:DT) excreted in urine after DM coadministration. Twenty-eight healthy
      extensive metabolizers of CYP2D6 received either venlafaxine (37.5 mg bid for 7
      days, then 75 mg bid until Day 28) or fluoxetine (20 mg daily for 28 days); 26
      completed the study. Plasma concentrations of both drugs and their active
      metabolites were determined. DM:DTs were evaluated at baseline (Day 0), on Days 7
      and 28 of dosing, and 2 weeks after drug discontinuation (Day 42). Steady-state
      drug and metabolite levels were achieved in both groups by Day 28. Mean DM:DTs
      for venlafaxine and fluoxetine differed statistically significantly (p < 0.001)
      on Days 7, 28, and 42. Comparisons of DM:DT as a percentage of baseline values
      showed that DM:DT increased 1.2-fold for venlafaxine and 9.1-fold for fluoxetine
      on Day 7 (p < 0.001) and increased 2.1-fold for venlafaxine and 17.1-fold for
      fluoxetine on Day 28 (p < 0.001). Inhibition of CYP2D6 metabolism persisted for 2
      weeks after discontinuation of fluoxetine, unlike the case with venlafaxine.
      These in vivo results confirm in vitro data demonstrating significantly weaker
      inhibition of CYP2D6 with venlafaxine than with fluoxetine. This suggests that
      clinically significant interactions involving CYP2D6 inhibition could occur
      between fluoxetine and drugs metabolized by CYP2D6 but may be less likely to
      occur with venlafaxine.

PMID- 11304902
TI  - Effect of alosetron on the pharmacokinetics of alprazolam.
AB  - Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist indicated for
      the treatment of irritable bowel syndrome (IBS) in females whose predominant
      bowel habit is diarrhea. Alosetron is extensively metabolized by multiple
      cytochrome P450 (CYP) enzymes, including CYP 2C9 and 3A4. Alprazolam is a short
      acting benzodiazepine commonly prescribed for the treatment of anxiety disorders
      and a potential comedication in patients with IBS. Alprazolam is extensively
      metabolized by CYP3A4. This clinical study was conducted to assess the potential
      for a metabolic drug interaction between these two CYP3A4 substrates. This was an
      open-label, randomized, two-period, crossover study in 12 healthy female and male
      volunteers to determine the effect of concomitant administration of alosetron at
      the recommended dose of 1 mg p.o. bid on the pharmacokinetics of alprazolam
      following a single oral 1 mg dose. The results showed no effect of alosetron on
      the pharmacokinetics of alprazolam. Mean alprazolam AUC was 210 and 202 ng.h/mL
      in the absence and the presence of alosetron, respectively. Therefore, alprazolam
      may be safely coadministered with alosetron without the need for dosage
      adjustment.

PMID- 11304903
TI  - Effect of alosetron on the pharmacokinetics of fluoxetine.
AB  - Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist indicated for
      the treatment of irritable bowel syndrome (IBS) in females whose predominant
      bowel habit is diarrhea. Alosetron is extensively metabolized by multiple
      cytochrome P450 (CYP) enzymes, including CYP2C9 and CYP3A4. Fluoxetine is an
      antidepressant that is administered as a racemic mixture of equipotent R- and S
      enantiomers. Fluoxetine metabolism involves CYP2D6 and CYP2C9 in the formation of
      its major metabolite, norfluoxetine. This metabolite is also present as two
      enantiomers, of which only the S-enantiomer exhibits comparable antidepressant
      activity. This study was conducted to assess the potential for an effect of
      alosetron on the pharmacokinetics of fluoxetine. This was an open-label, two
      period, nonrandomized, crossover study in 12 healthy female and male volunteers.
      The pharmacokinetics for both enantiomers of fluoxetine and norfluoxetine were
      examined following single oral doses of 20 mg fluoxetine, given alone and in
      combination with alosetron 1 mg twice daily for 15 days. The results showed small
      delays in peak concentration but no clinically significant effect of alosetron on
      the pharmacokinetics of S- and R-fluoxetine or S- and R-norfluoxetine.
      Coadministration of alosetron and fluoxetine was well tolerated by all subjects.

PMID- 11304904
TI  - The stereoselective effects of bucolome on the pharmacokinetics and
      pharmacodynamics of racemic warfarin.
AB  - The objective of this study was to investigate the stereoselective influence of
      bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese
      inpatients with heart disease. Thirty patients were administered a fixed
      maintenance dose of warfarin alone once a day for at least 7 days. The other 25
      patients were concomitantly administered warfarin and a 300 mg dose of bucolome
      once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after
      administration of bucolome. Serum concentration of warfarin enantiomers was
      measured by a chiral reversed-phase HPLC-ultraviolet detection method. The PT-INR
      was used as a measure of the pharmacodynamic effect of warfarin. Coadministration
      of bucolome and warfarin had no effect on serum (R)-warfarin concentration and
      significantly increased serum (S)-warfarin concentration compared with warfarin
      alone. The PT-INR of warfarin alone was significantly lower with bucolome
      cotreatment. These results indicate that the augmented anticoagulant effect of
      warfarin by bucolome is due to inhibition of (S)-warfarin metabolism in vivo.
      When bucolome is added to a stabilized regimen of warfarin therapy, the dose of
      warfarin should be reduced by about 30% to 60%, and caution should be exercised
      during the first 7 days after coadministration of bucolome.

PMID- 11304905
TI  - Decrease of intracranial pressure and weight with digoxin in obesity.
AB  - Fourteen obese patients (body mass index = 34-47 kg/m2; mean = 40 kg/m2) with
      lumbar cerebrospinal fluid pressure (Pcsf) above 20 cm water in 10 of the 14
      patients were treated with digoxin with a serum concentration of at least 1.0
      nmol/L (0.8 ng/ml) for 6 months. Pcsf decreased significantly during digoxin
      medication (p < 0.005). Although there were no diet restrictions, all patients
      decreased in weight (range: 3-25 kg; mean = 10.6 kg) during the 6 months (p <
      0.001). When digoxin medication was stopped in 3 patients, prompt weight increase
      occurred. Most patients needed progressively increased digoxin doses to attain
      stabilized serum concentrations at the stipulated level, in 5 patients more than
      0.5 mg a day. Five of 13 patients developed diabetes mellitus during the digoxin
      medication. The larger the dose of digoxin, the greater the risk for diabetes
      mellitus to occur.

PMID- 11304906
TI  - Nutrition and prostate cancer: a proposal for dietary intervention.
AB  - In this review, we consider the evidence from geographic and metabolic
      epidemiology and laboratory studies with human prostate cancer cell lines and
      animal models that emphasizes the need for the development and implementation of
      a dietary intervention trial in prostate cancer patients. It is concluded that
      such a trial should include a reduction in total fat consumption to 15% of total
      calories and supplementation of the diet with selenium, vitamin E, and a soya
      product. The low-fat intervention would provide an appropriate reduction in the
      intake of any specifically targeted dietary fatty acid, such as linoleic acid or
      alpha-linolenic acid.

PMID- 11304907
TI  - Intestinal cell proliferation is influenced by intakes of protein and energy,
      aflatoxin, and whole-body radiation.
AB  - Intestinal epithelial cell proliferation in young male F344 rats was measured in
      response to dietary protein content (5%, 10%, and 20% casein diets), energy
      restriction (energy intake was 60% of ad libitum energy intakes of animals
      consuming the 20% casein diet), total diet restriction (dietary intake was 60% of
      the ad libitum intake of 20% casein diet group), aflatoxin administration, and
      whole body irradiation. Cellular proliferation was measured in sections of
      jejunum, ileum, proximal colon, and distal colon with the [3H]thymidine
      technique. Restricting energy or total diet intakes by 40% from ad libitum levels
      reduced proliferation in epithelial cells throughout the intestine. In comparison
      to the 5% casein diet, the 20% casein diet resulted in modestly lower cellular
      proliferation in all intestinal segments. Radiation induced a decrease in
      cellular proliferation in the jejunum and ileum; this decrease was prevented by a
      20% casein diet. Pretreatment with aflatoxin B1 decreased intestinal cell
      proliferation throughout the intestine, and this decrease was not influenced by
      the protein content of the diet.

PMID- 11304908
TI  - The effect of treadmill exercise on azoxymethane-induced intestinal neoplasia in
      the male Fischer rat on two different high-fat diets.
AB  - A total of 120 eight-week-old male rats were exposed to azoxymethane (15 mg/kg
      body wt in saline s.c.) on Days 1, 4, and 8. Two days after the last injection of
      carcinogen, the rats were randomized into four experimental groups: two groups
      were given a chow high in corn oil (23% corn oil) and two groups a chow high in
      coconut oil (21% coconut oil and 2% corn oil). One group on each chow was kept
      sedentary, and one group was exposed to moderate exercise, running 2 km/day on
      weekdays for 38 weeks. At the end of the experiment, the exercising and sedentary
      rats fed coconut oil were significantly heavier than those fed corn oil. Among
      the rats fed the high-fat corn oil diet, exercise reduced the number of animals
      developing carcinomas in the colon (sedentary, 10; exercise, 0) and in the small
      intestine (sedentary, 5; exercise, 0). The same tendency was observed in the rats
      fed the coconut oil diet: colon (sedentary, 6; exercise, 3) and small intestine
      (sedentary, 3; exercise, 2). In the sedentary rats fed the high corn oil diet, 16
      intestinal carcinomas were recorded; none were found in the exercised group. In
      the rats fed the high coconut oil diet, nine carcinomas were recorded in the
      sedentary groups as opposed to five in the exercised rats. Rats fed the high-fat
      coconut oil developed significantly fewer neoplasms than the rats fed the equally
      high-fat corn oil diet.

PMID- 11304909
TI  - Effects of type and amount of dietary fat on mouse skin tumor promotion.
AB  - In a previous study (Cancer Res 51, 907, 1991) in which we found an inverse
      relationship between quantity of dietary corn oil and saturated fat, in a
      constant 15% fat diet, on the tumor promotion stage of skin carcinogenesis, it
      was not clear whether one or both types of fat played a modulatory role. The
      purpose of the present study therefore was to compare the effect of 1) increasing
      corn oil in corn oil-only diets and 2) increasing saturated fat, with a constant
      level of 5% corn oil, on tumor promotion. In the first study, the effects of five
      levels of dietary corn oil (5%, 10%, 15%, 20%, and 25%) on the incidence and rat
      of papilloma and carcinoma development were determined in female Sencar mice fed
      these diets one week after initiation with 7,12-dimethylbenz[a]anthracene and
      three weeks before the start of promotion with 12-O-tetradecanoylphorbol-13
      acetate. A papilloma incidence of 100% was reached first in the 5% corn oil
      group, at 10 weeks, followed by the 10% group at 13 weeks and the 15% and 20%
      group at 16 weeks. The highest corn oil group achieved a 90% incidence. There
      were marked differences in latency of carcinoma development among the diet
      groups. At Week 29, the cumulative carcinoma incidence was 56% and 32%,
      respectively, in the 5% and 10% corn oil groups, whereas the incidence in the two
      highest corn oil (20% and 25%) groups was only 8% and 4%, respectively. In the
      second study, the effects of diets containing 5% corn oil and increasing levels
      of coconut oil (5%, 10%, 15%, and 20%) on the incidence and rat of papilloma and
      carcinoma development were determined, as described above. No significant
      difference in latency or incidence of papillomas or carcinomas was noted among
      these saturated fat diet groups. It thus appears that higher levels of dietary
      corn oil are associated with a reduced cancer incidence in this model system.

PMID- 11304910
TI  - Alcohol consumption and the risk of gastric cancer.
AB  - The relationship between alcohol drinking and gastric cancer risk was analyzed
      using data from a case-control study conducted in Northern Italy between 1985 and
      1993 on 746 cases of histologically confirmed incident stomach cancer and 2,053
      controls in hospital for acute nonneoplastic nondigestive tract diseases. Wine
      was the most frequently consumed alcoholic beverage, accounting for approximately
      90% of all alcohol consumption. Compared with those who never drank wine, the
      odds ratios (OR) were 1.1 [95% confidence interval (CI) 0.9-1.3] for fewer than
      four drinks per day, 1.3 (95% CI 1.0-1.7) for four to fewer than six drinks per
      day, 1.6 (95% CI 1.1-2.4) for six to fewer than eight drinks per day, and 1.4
      (95% CI 1.0-2.0) for eight or more drinks per day. No association was observed
      with beer or spirits. For total alcohol consumption, 25% of cases and 30% of
      controls never drank alcohol, and the multivariate OR for those who drank versus
      those who did not drink was 1.1 (95% CI 0.9-1.4). After allowance for smoking,
      education, family history of stomach cancer, selected micronutrient intake, and
      nonalcohol calorie intake, the ORs were 1.1 (95% CI 0.9-1.4) for fewer than six
      drinks per day, 1.0 (95% CI 0.4-1.4) for six to fewer than eight drinks per day,
      and 1.3 (95% CI 0.9-1.9) for eight or more drinks per day, and the trend in risk
      was not significant. No interaction was observed between alcohol drinking and
      sex, family history, and smoking, but the association with alcohol drinking was
      appreciably stronger in the elderly and in less-educated individuals. Thus this
      large data set was able to exclude a strong and consistent association between
      alcohol (mainly wine) drinking and stomach cancer risk. A nonsignificant
      association was observed in those who drank very heavily, but the absence of a
      dose-risk relationship suggests that even such a moderate association may reflect
      inadequate allowance for covariates or the presence of other risk factors
      (possibly related to diet and social class) among the heaviest drinkers.

PMID- 11304911
TI  - Helicobacter pylori-associated gastritis and the ascorbic acid concentration in
      gastric juice.
AB  - Patients infected with Helicobacter pylori have abnormally low ascorbic acid
      concentration in gastric juice. Low vitamin C intake and Helicobacter pylori
      infection have been related to an increased risk of gastric carcinoma. This
      report examines the association between ascorbic acid and Helicobacter pylori in
      patients referred for upper gastrointestinal endoscopy. Elevated gastric pH and
      the damage to the gastric surface epithelium were inversely associated with the
      ascorbic acid concentration in gastric juice. We postulate that these two factors
      mediate the ascorbic acid-decreasing effect of Helicobacter pylori. Patients with
      nonpremalignant conditions (normal gastric histology, diffuse antral gastritis,
      or duodenal ulcer) had lower gastric pH, less damage to the gastric epithelium,
      and higher levels of ascorbic acid in gastric juice than patients with atrophic
      gastritis, intestinal metaplasia, or dysplasia.

PMID- 11304912
TI  - Diet and oral premalignancy in female south Indian tobacco and betel chewers: a
      case-control study.
AB  - The diets of 158 tobacco/betel quid-chewing women diagnosed with oral
      premalignant lesions and 155 quid-chewing but lesion-free controls, frequency
      matched for age, tobacco/betel habits, and socioeconomic status, were assessed
      using a food frequency survey. Index scores generated from the food frequency
      survey indicated that the mean levels of consumption for foods of animal origin
      (p < 0.001), total vegetables and fruit (p = 0.001), vegetables alone (p =
      0.006), fruits alone (p = 0.006), and green leafy vegetables (p = 0.015) were
      significantly lower in cases than in controls. The mean index score for cobalamin
      (vitamin B12) was lower in cases with a borderline significance (p = 0.05),
      whereas the indexes for folate and carotene were not significantly different. The
      analysis of index scores estimating the number of 100-g servings per week of
      foods of animal origin [meat, eggs, milk, curd (yogurt), fish] consumed revealed
      that women who ate fewer servings were more likely to have premalignant lesions
      than those who ate more animal foods [odds ratio (OR) 3.38, 95% confidence
      interval (CI) 2.07-5.54, p = 0.001]. The risk for low consumption of vegetables
      was not as significant as that for foods of animal origin. However, those eating
      low levels of vegetables and low levels of foods of animal origin were at the
      greatest risk for lesions (OR 5.38, 95% CI 1.72-22.17, p < 0.05). In South Indian
      female tobacco/betel chewers, a diet deficient in foods of animal origin appears
      to be a more significant risk factor for oral premalignancy than is a diet
      deficient in fruits and vegetables.

PMID- 11304913
TI  - Cancer mortality and age: relationship with dietary fat.
AB  - Highly significant correlations exist between total cancer mortality and age
      expressed by a log total cancer mortality-log age equation (mean r2 0.991 in men
      and 0.996 in women) or by a second-order polynomial equation including age and
      age2 (mean r2 0.999 in men and 0.998 in women). In all countries considered (n =
      32), the second-order term of age is negative, indicating a decrease in the rate
      of rise of log cancer mortality at older age. This could be explained by a lesser
      accuracy of the diagnosis of cancer at older age, by selective survival of
      subjects resistant to cancer, by a cohort effect, or by a decrease in the rate of
      growth of cancer at older age. The decrease in the rate of rise of cancer
      mortality after 65 years of age occurs in all countries and applies to nearly all
      cancers except breast cancer in women after 75 years of age. A high cancer
      mortality in a country is characterized by a low intercept and a steep slope of
      the log mortality-log age equation. These parameters are influenced by dietary
      fat intake in men and women, with saturated fat increasing total cancer mortality
      and the ratio of polyunsaturated to saturated fat and the ratio of unsaturated to
      saturated fat decreasing it. The data on dietary fat were obtained from the Food
      and Agriculture Organization of the United Nations (FAO) food balance sheets (n =
      32) and from dietary surveys (n = 21). Both vary in the same direction, but only
      the dietary data from the FAO correlate significantly with cancer mortality. This
      finding points toward a relationship between the level of dietary fat intake and
      total cancer mortality at the population level.

PMID- 11304914
TI  - Dynamics of virulence of Plasmodium falciparum.

PMID- 11304915
TI  - Naturally occurring plasmodia-specific circulating immune complexes in
      individuals of malaria endemic areas in India.
AB  - Blood samples collected from individuals belonging to malaria endemic areas were
      assayed for antigen-specific circulating immune complexes in polyethylene glycol
      precipitates of serum by enzyme immunoassay. Sera were tested from patients with
      acute P. vivax and P. falciparum infections, from clinically immune individuals
      and also from healthy normals. Circulating immune complexes (CICs) containing
      immunoglobulin G and M isotypes were found to be abundant in individuals with
      ongoing and past infections and also in clinically immune donors. In patients
      with acute infection but without any past history of malaria, CICs of IgM type
      were found to be significantly higher. Demonstration of antigen/antibody specific
      CICs could be a useful indicator of active, ongoing and recent/past infection,
      also of the status of immune responses of individuals belonging to various
      endemic areas.

PMID- 11304916
TI  - Population dynamics of mosquito immatures and the succession in abundance of
      aquatic insects in rice fields in Madurai, South India.
AB  - Studies on the breeding pattern of mosquito immatures and the successional
      changes in the abundance of aquatic insects were conducted in rice fields near
      Madurai, south India. The population of late (III/IV) larval instars of culicines
      peaked on Day 28 and pupae (Culex tritaeniorhynchus, Cx. pseudovishnui and Cx.
      vishnui) peaked on Day 9 after transplantation, whereas the population of late
      (III/IV) larval instars of anophelines peaked on Day 19 and pupae of Anopheles
      subpictus and An. vagus on Days 7 and 9 respectively, after transplantation of
      paddy. A total of 14 families (consisting of 17 subfamilies) of aquatic insects
      belonging to six different orders, Coleoptera, Diptera, Ephemeroptera, Hemiptera,
      Anisoptera and Zygoptera were collected during the study period and the abundance
      of each group of insects is discussed in detail. The Shannon-Weaver Diversity
      Index, applied to study the diversity of different groups of aquatic insects,
      showed a clear pattern in diversity of surface predators, bottom predators and
      non-predators of mosquito immatures. The multiple linear regression model reveals
      that notonectid adults, coenagrionids, libellulids and veliids act as important
      predators of mosquito immatures in rice fields.

PMID- 11304917
TI  - Patterns of parasitaemia, antibodies, complement and circulating immune complexes
      in drug-suppressed simian Plasmodium knowlesi malaria.
AB  - Rhesus monkeys were inoculated intravenously with 1 x 10(4) P. knowlesi infected
      erythrocytes. After about three days prepatency, peripheral smears were found
      positive and the animals were cured with chloroquine phosphate when parasitaemia
      reached about 15-25 per cent. The monkeys were repeatedly exposed with three
      bouts of infection. The first and second bouts were cured but after the third
      challenge, all 10 monkeys showed a longer prepatent period, lower parasitaemia
      and then self-recovery. Sera were collected in different phases of infection to
      assess immune responses. Antimalarial IgG and IgM responses were measured by
      ELISA. The presence of IgM antibody was associated with every bout of infection.
      With repeated infections until self-recovery, a substantial amount of IgG was
      found in circulation. A significant level of schizont-infected cell agglutination
      antibody was also detected in the animals after survival from challenge
      infection. Antigen-specific circulating immune complexes, both of IgG and IgM
      types, appeared in various phases of infection, but their appearance did not
      coincide with the acquired immune responses of the animals. During the self
      recovery phase, almost all monkeys had an elevated level of serum C3 and C4.

PMID- 11304918
TI  - A controlled study on haemograms of malaria patients in Calcutta.
AB  - A study was carried out at the Urban Health Centre, Chetla, Calcutta to evaluate
      the efficacy of quantitative buffy coat (QBC) analysis of haemograms in malaria
      patients suffering from fever with bodyache and chill and/or rigour attending the
      Fever Treatment Depot during a three months period (March-June 1996) who had
      undergone both malaria parasite study and haematological investigation by the QBC
      method from blood samples collected by finger prick. To avoid bias, malaria
      parasite studies and haemograms were done separately, and investigators were kept
      'blind' about the results of other investigations. The haematological findings
      obtained of 180 slide-positive malaria cases were compared with a sample of 177
      age- and sex-matched slide-negative controls selected by random sampling. The
      results revealed that haemoglobin levels (g%), haematocrit values (%), WBC and
      platelet counts of malaria cases were significantly lower than in the matched
      controls. Thus, QBC estimation correlates well with existing knowledge about
      malarial haematology. This relatively easier, quicker and reliable method of
      taking haemograms may be recommended for field testing for assessing
      haematological parameters of malaria cases under field conditions, before its
      introduction for large-scale use.

PMID- 11304919
TI  - Comparative study on microscopic detection of malarial parasites under
      conventional thick film and concentration by saponin haemolysis.

PMID- 11304920
TI  - [Unintentional gunshot during police intervention].
AB  - 33 cases of unintentional handgun use by police officers during operation since
      1983 in Northern Germany have been evaluated. These cases have been selected from
      our own investigations and from prosecutors' and police departments' files and
      records. It was intended to find out criteria for forensic expertise. The
      unintended use of a handgun was always influenced in a decisive and causal manner
      by the behaviour of the delinquents (resistance, assault, escape). The
      confrontation of the police officer with the violence of aggressive offenders was
      of immediate importance for triggering the shot in various kinds of police
      operation. Sensorically caused, reflex muscle contractions as a consequence of a
      great effort, a loss of balance or fright when simultaneously protecting oneself
      with weapon in hand can be made responsible for the unvoluntary shot. In 10 cases
      (30%) persons were injured, 2 times lethally. As a whole, the consequences were
      of random nature, they could be explained by the series of actions in each case.
      The type and technical state of the weapons in use have not influenced the
      unintentional use. A behaviour of the police officers offending against the
      legally required care was stated in two of the investigated cases. Considering
      our investigations and the many policemen killed in duty we state that securing
      oneself in time with a weapon at the ready in critical phases of operations
      cannot be successfully replaced by any other method of self defense.

PMID- 11304921
TI  - [Perpetrator related analysis of intentional homicides in the Genf canton (1971
      1990)].
AB  - A retrospective offender-related analysis was conducted on all deliberate
      homicides committed in the canton of Geneva between 1971 and 1990. The cases
      analyzed included 97 convicted single perpetrators or accomplices and 93 victims.
      21 further homicides remained unsolved. 86.6% of the offenders were male;
      foreigners were over-represented in comparison with Swiss citizens. The average
      age was 35 years. In a majority of the cases the offender and the victim were
      partners, came from the same family or were acquainted with each other. Guns or
      knives were the most frequently used weapons. The criminal offences tried in
      Geneva were evaluated also with regard to their legal qualification.

PMID- 11304922
TI  - [Death caused by accidental hanging in the hand strap loop of a garage door].
AB  - The authors report on a 10-year-old boy who accidentally hanged himself in the
      hand strap of a garage door. The door was an electric overhead door of an
      underground garage. The accident was reconstructed at the scene using a dummy.
      The strap of the door was long enough to be slipped over the head easily. In view
      of this background it seems advisable to consider whether the current safety
      regulations on the operation of electric doors should be changed accordingly.

PMID- 11304923
TI  - [Once again: risk of injury caused by blank pistols].
AB  - The nature and extent of the use of blank pistols in Hamburg (according to the
      Hamburg crime statistics about 300 to 400 such cases per year; 34 cases involving
      head and neck wounds from 1989 to 1999 were investigated at our institute; among
      these 8 suicides, no homicide) as well as patterns of injuries caused by close
      distance blank pistol shots were analysed. 7 of these cases are described in
      detail. The results of our studies corroborate the warning statements made by
      many criminological and medico-legal experts regarding the danger inherent in
      these allegedly harmless weapons. Blank cartridge pistols can, when shot from a
      close distance, cause most severe injuries involving penetration into body
      cavities and bodily organs (especially in the head and neck), and even
      perforation of the skull. Therefore, we call for a much stricter control of
      weapons of this kind.

PMID- 11304925
TI  - [Differential burns of head and pubic hair].
AB  - A woman, who was hospitalized with extensive burns in the genital and perineal
      region, accused her husband who lived apart from her to have inflicted the
      injuries with a lighter and a burning candle out of jealousy. The husband denied
      the accusations and stated that he wanted to singe off the pubic hair with the
      lighter during sadomasochist sexual practices performed in mutual agreement. As
      he did so extensive flames suddenly developed--something he had not expected-
      thus causing the burns. To check the statement cut off tufts of head and pubic
      hair were set on fire with a lighter to compare their burning behaviour. Pubic
      hair was easily inflammable and burnt almost completely within about 10 seconds
      developing up to 10 cm high flames, whereas straight head hair developed only
      minor flames and the singed hairs stopped burning spontaneously some seconds
      later already.

PMID- 11304924
TI  - [Plastic bag as the method in suicide and homicide].
AB  - The report describes a suicide and a homicide by suffocation in a plastic bag.
      Both cases were copy-cat acts. The suicide copied the method--taking medicines
      and pulling a plastic bag over his head from a personal model. In the homicide
      the perpetrator followed the example of a film sequence from the US feature film
      "Charade".

PMID- 11304926
TI  - [Criminal process record Winckelmann (Triest, 1768). Comments on the criminal
      process dealing with the murder of Johann Joachim Winckelmann from the forensic
      historical and legal medicine viewpoint].
AB  - Johann Joachim Winckelmann, German historian of ancient art and archaeologist,
      was born on 9 December 1717 in Stendal, a town in Saxony-Anhalt. At the age of 50
      he was murdered on 8 June 1768 in a Trieste hotel. The voluminous original record
      of the criminal proceedings against his murderer, Francesco Arcangeli, was
      presumed lost for about 150 years. A new edition in the wording of the original
      text appeared in 1964. This long sought historical document gives cause for
      forensic-historical reflections under consideration of the autopsy protocol about
      Winckelmann, which is likewise a historical document. A considerable change of
      paradigm in comparison to current autopsy protocols is observed with regard to
      the evaluation of injuries and the circumstances of death.

PMID- 11304927
TI  - Surgically assisted rapid palatal expansion. An acoustic rhinometric,
      morphometric and sonographic investigation.
AB  - This study aimed to evaluate the effect of surgically assisted rapid palatal
      expansion on the skeletal structures of the midface. Ten patients (mean age 28.5
      years) were investigated by means of acoustic rhinometry, study model analysis
      and sonography before and after the procedure of surgically assisted rapid
      palatal expansion. The measurements revealed that surgically assisted rapid
      palatal expansion not only resulted in transverse expansion of the maxilla,
      providing dental arch space for lining up the teeth; the procedure also caused a
      substantial enlargement of the maxillary apical base and of the palatal vault,
      providing space for the tongue for correct swallowing and thus preventing
      relapse. There was a distinct subjective improvement in nasal breathing
      associated with enlargement of the nasal valve towards normal values and with an
      increase of nasal volume in all compartments. The measurements showed a marked
      influence of surgically assisted rapid palatal expansion on the skeletal
      structures of the midface. The significant widening can be demonstrated by non
      invasive examination. Success of the osteotomy procedure can be readily monitored
      by sonographic examination of the expansion and the subsequent ossification,
      which allows individually adjusted retention periods and avoids frequent
      radiation exposure.

PMID- 11304928
TI  - Reliability and validity of the Digigraph 100 in orthodontic diagnosis.
AB  - Cephalometric analyses of lateral cephalograms allow important statements to be
      made on diagnosis and treatment planning. Such radiographs should, however, be
      taken with a considerable reduction in radiation exposure. With the Digigraph 100
      (Dolphin Imaging Systems Inc., USA) a cephalometric technique based on distance
      measurements of emitted sonic signals is now available. This study was aimed at
      determining the degree to which this procedure can cope with the requirements of
      reliability and validity in the field of orthodontics. For this purpose 50
      volunteers were examined by conventional cephalometry with manual tracing of
      lateral cephalograms as well as by sonic cephalometry, with Jarabak analysis in
      both cases. In addition an option was available for reading lateral cephalograms
      into the Digigraph by means of a radiograph evaluation program. The 31 evaluated
      parameters were subjected to modified statistical analysis. Good reliability was
      recorded in the range between 0.96 and 0.99 for eleven sonic cephalometric
      measurements, whereas 26 values were between 0.69 and 0.95. The validity was
      significantly lower in comparison to radiocephalometry. In particular,
      measurements related to landmarks which were difficult to access or could be only
      indirectly determined, such as the sella point, the articulare point or the
      apices of the incisors, proved to be weak points of sonic cephalometry. The
      device is thus indicated rather in the field of communication with the patient or
      for intermediate examination without radiation exposure. Cephalometry without
      radiation exposure would represent decisive progress in orthodontic diagnostics.
      However, some developmental work on the processing software or even the
      development of a specific sonic cephalometry which deliberately dispenses with
      parameters that are difficult to record with this procedure is still needed.

PMID- 11304929
TI  - Mouth opening and its influencing through the SII appliance during the night.
AB  - In twelve patients, 43 nocturnal sleep investigations were carried out
      telemetrically. These investigations were aimed at contributing towards answering
      the questions of how large the interocclusal distance is during the night,
      whether there is a correlation with the growth pattern, and whether this
      interocclusal distance can be changed by using Class II elastics. The treatment
      appliance chosen was the SII appliance. During nocturnal sleep, all patients
      slept with their mouth more or less open. The largest interocclusal distance was
      found in patients with a vertical growth pattern as well as in one patient in
      whom an allergic reaction to the house dust mite was later verified. The active
      phase during nocturnal sleep comprised between 200 and 800 biting actions during
      the entire sleeping period and corresponded to an activity of about 10 minutes.
      During nocturnal sleep there were rarely complete mouth closures, even during
      diverse swallowing actions. Patients with a horizontal growth pattern showed the
      smallest interocclusal distance, provided that nasal breathing was not
      obstructed. The additional application of Class II elastics had a positive effect
      on the interocclusal distance in all patients. A shortening of the protrusive
      bars must be avoided in all events; otherwise there may be no protrusion when
      biting together. The long bars of the SII appliance have an influence on the
      maxilla, because there is contact between maxilla and mandible up to mouth
      openings of about 14-16 mm.

PMID- 11304930
TI  - Effects of orthodontic bands on marginal periodontal tissues. A histologic study
      on two human specimens.
AB  - Eight banded teeth on two human specimens (9 years, male; 19 years, female) were
      analyzed regarding the fit of the orthodontic bands and periodontal reactions.
      Five teeth (three molars, two premolars) were evaluated histologically in the
      horizontal plane and three (one molar, two premolars) in the sagittal plane using
      the micro-section method according to Donath. The fit of the bands varied in
      occluso-apical direction. The mean of marginal gaps was x = 0.23 mm in the
      occlusal, x = 0.03 mm in the equatorial, and x = 0.28 mm in the cervical area. In
      the equatorial area the thin cement layer was largely homogeneous, whereas
      porosities and microfissures were found predominantly in thicker cement layers.
      85% of the occlusal and cervical band margins revealed cement defects and/or
      erosions which were colonized by felted, partially densely compacted microbial
      plaque. With regard to the periodontal effects, the signs of inflammation in the
      buccolingual gingival areas were markedly less severe due to the supramarginal
      position of the band margins. The interdental gingiva of all teeth presented the
      histological pattern of an established gingival lesion. Leukocyte infiltration
      and inflammatory exudation in the area of the transseptal fibers were
      exceptionally pronounced in one lower molar (band exposure time: 6 months). At
      this site the connective tissue attachment close to the cementoenamel junction
      was severely damaged on the mesial surface and the pocket epithelium proliferated
      towards the apex, meaning progression from established gingivitis to an initial
      periodontal lesion. The histologic findings on these human periodontal tissues
      confirm that the application and hygiene control of orthodontic bands have to be
      performed with great care to avoid permanent periodontal destruction.

PMID- 11304931
TI  - Early treatment of angle Class II, division 2 in combination with functional
      therapy of TMJ fracture.
AB  - Children who have sustained condylar fractures are treated with functional
      appliances because surgical repositioning of the condyle is more resource
      intensive without producing better results. In cases with additional
      malocclusions it is practicable to combine the functional therapy of the fracture
      with skeletal Class II therapy. A 10-year-old boy suffering from a left condylar
      fracture and showing Class II, Division 2 malocclusion was treated with a
      skeletal functional appliance in combination with a utility arch for uprighting
      of the incisors. A modified transpalatal bar was then used to retain the incisor
      position. The remodeling process of the mandibular condyle following its fracture
      with dislocation signifies a high adaptability of the affected tissues. This
      reaction can be used simultaneously for effective sagittal repositioning of the
      mandible in certain cases of Class II malocclusion.

PMID- 11304932
TI  - Fixed lingual arch appliance for compliance-free unilateral molar distalization
      in the mandible.

PMID- 11304933
TI  - Size discrepancy of apical bases and treatment success in angle Class III
      malocclusion.
AB  - The aim of this retrospective clinical study was to measure the apical bases and
      determine their size relationship in Class III malocclusion cases before and
      after orthodontic treatment, in order to evaluate their significance for the
      treatment success. Maxillary and mandibular apical bases were measured on study
      models of 104 Class III cases treated by conventional orthodontics, using a
      specifically constructed conveyance apparatus, and related to each other as an
      index. Treatment success was quantitatively assessed as the percentage change of
      PAR scores obtained from the pretreatment and posttreatment study models.
      Statistically significant relationships were disclosed between the measurements
      of the apical bases and several other evaluated parameters. The results obtained
      indicate a high prognostic value of the size relationship of the apical bases for
      the treatment success of Class III malocclusion.

PMID- 11304934
TI  - Bioavailability investigation of two different oral formulations of doxepin.
AB  - Two different oral doxepin (CAS 1668-195) formulations (Doxepin-ratiopharm 25 mg
      film-coated tablets as test preparation and 25 mg dragees of the reference
      preparation) were investigated in 30 healthy male and female volunteers in order
      to prove bioequivalence between these preparations. A single 75 mg oral dose (3
      units of test or reference preparation) was given according to a randomised two
      way cross-over design in the fasted state. Blood samples for determination of
      plasma concentration of doxepin and its metabolite N-desmethyldoxepin were
      collected at pre-defined time points up to 168 h following drug administration. A
      wash-out period of three weeks separated both treatment periods. Doxepin and N
      desmethyldoxepin plasma concentrations were determined by means of a validated LC
      MS/MS method. Values of 193,463 pgh/ml (test preparation) and 197,988 pg h/ml
      (reference preparation) for doxepin as well as values of 313,298 pg h/ml (test
      preparation) and 306,663 pgh/ml (reference preparation) for N-desmethyldoxepin
      for the parameter AUC0-infinity demonstrate a nearly identical extent of drug
      absorption. Maximum concentrations (Cmax) for doxepin/N-desmethyldoxepin of
      15,960.06/6,883.69 pg/ml and 18,614.73/6,846.62 pg/ml were achieved for test and
      reference preparation. Time to reach doxepin maximum plasma concentration (tmax)
      was 1.98 h for both preparations and for N-desmethyldoxepin tmax was 4.52 h (test
      preparation) and 4.15 h (reference preparation). Cmax and AUC0-infinity values
      were tested for statistically significant differences by means of the Two One
      Sided T-Tests procedure following ln-transformation of data. Bioequivalence was
      assumed if the 90% confidence intervals of the T/R-ratios were in the range of
      80%-125% for ln-transformed AUC0-infinity and 70%-143% for ln-transformed Cmax.
      Based on the results obtained in this study, bioequivalence between the test and
      the reference preparation was demonstrated.

PMID- 11304935
TI  - Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor, in guinea pig model of hyperlipidemia.
AB  - Although benefits of statins have been demonstrated even in normolipidemic
      patients at high risk, the main target of statin therapy is the
      hypercholesterolemic patient. The aim of this study was to examine the
      hypocholesterolemic effect of NK-104 ((+)-monocalcium bis((3R,5S,6S)-7-[2
      cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]- 3,5-dihydroxy-6-heptenoate), CAS
      147526-32-7), a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitor, and its mechanism of action in hypercholesterolemic animals. In guinea
      pigs fed a diet containing 15% (w/w) fat rich in laurate for 6 weeks, the liver
      cholesterol content was markedly increased and plasma total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C) and LDL-apoB were elevated 4.8, 5.2 and
      1.7 times, respectively, compared with normal diet fed animals. These changes
      were maintained by reduced LDL clearance in the presence of markedly cholesterol
      enriched LDL in the plasma. In this model, the LDL-C reduction rates by 0.1, 0.3
      and 1 mg/kg of NK-104 orally administered for 2 weeks (from week 4 to week 6),
      were 11, 27 and 32%, respectively, from controls, being similar in normal guinea
      pigs previously examined. Those for 3 and 10 mg/kg of atorvastatin (CAS 134523-00
      5) were 25 and 39%, respectively. Thus about 10 times higher doses of
      atorvastatin were required than of NK-104 to cause a similar cholesterol-lowering
      effect. This reduction of plasma cholesterol was accompanied by an improvement of
      LDL clearance (24 and 47% increase in fractional catabolic rate by 1 mg/kg of NK
      104 and 10 mg/kg of atorvastatin, respectively) and LDL composition. In
      conclusion, in guinea pig hypercholesterolemia caused by high-laurate diet, NK
      104 and atorvastatin lowered plasma cholesterol levels with an improvement of LDL
      composition and with an increase in LDL clearance, presumably through reduction
      of the liver cholesterol content, although hepatic cholesterol synthesis might
      have been markedly suppressed in this model.

PMID- 11304936
TI  - Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid
      secretion in vitro and in vivo.
AB  - The inhibitory effects of IY-81149 (2-[[(4-methoxy-3-methyl)-2- pyridinyl]methyl
      sulfinyl]-5-(1H-pyrol-1-yl)-1H-benzimidazole, CAS 172152-36-2), a newly developed
      proton pump inhibitor (PPI) on gastric acid secretion were investigated in vitro
      and in vivo. In rabbit parietal cell preparation, IY-81149 irreversibly inhibited
      H+/K(+)-ATPase in dose-dependent manner with an IC50 of pump inhibitory activity
      of 6.0 x 10(-6) mol/l and that of omeprazole (CAS 73590-58-6) was 1 x 10(-4)
      mol/l at pH 7.4. On cumulation of 14C-aminopyrine in histamine stimulated
      parietal cells, the IC50 of IY-81149 was 9.0 x 10(-9) mol/l and that of
      omeprazole was 1.9 x 10(-8) mol/l. The inhibition rates of IY-81149 and
      omeprazole at a concentration of 1 x 10(-9) mol/l in human parietal cells were
      137% and 64%, respectively. In pylorus-ligated rats, IY-81149 showed a 2-3 times
      stronger inhibitory activity than omeprazole against gastric acid secretion. The
      ED50 of IY-81149 and omeprazole administered intraduodenally was 1.6 mg/kg and
      3.8 mg/kg. In the case of oral administration, the ED50 of IY-81149 and
      omeprazole was 1.94 mg/kg and 5.64 mg/kg, respectively. But after 24 h
      administration, the anti-secretory activity of IY-81149 was lower than that of
      omeprazole at all doses tested. In anesthetized rats, IY-81149 dose-dependently
      increased gastric pH which was lowered by histamine infusion. In the case of i.v.
      injection, the ED50 of IY-81149 and omeprazole was 1.2 and 1.4 mg/kg and in the
      case of i.d. administration, the ED50 of IY-81149 and omeprazole was 3.9 and 4.1
      mg/kg, respectively. IY-81149 also significantly inhibited pentagastrin
      stimulated gastric secretion. Its ED50 was 2.1 mg/kg and that of omeprazole was
      3.5 mg/kg with i.d. administration. In the case of i.v. injection, IY-81149 was
      equipotent to omeprazole. IY-81149 also inhibited gastric acid secretion strongly
      in fistular rats. The ED50 of IY-81149 administered intraduodenally was 0.43
      mg/kg and that of omeprazole was 0.68 mg/kg. In Heidenhain pouch dogs, the acid
      output was completely blocked at 0.3 mg/kg, 135 min after i.v. administration.
      Omeprazole showed a similar effect as IY-81149. The histamine induced increase of
      acid output in the Heidenhain pouch dog was blocked by 71% 150 min after oral
      administration of enteric-coated IY-81149 at a dose of 3 mg/kg, and omeprazole
      showed similar effects. In conclusion, IY-81149 revealed the characteristics as a
      strong proton pump inhibitor, and its potency against gastric acid secretion was
      superior to that of the reference drug, omeprazole.

PMID- 11304937
TI  - Effect of nilvadipine in weak acidic medium by 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) assay.
AB  - A new medium (pH 5.6 reached by addition of 0.1 mol/l acetate buffer, 37 degrees
      C, 60 min) was established for detecting anti-free radical compounds in the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) assay. DPPH bleaching activities of typical
      antioxidants appeared generally weaker at pH 8.0 (the measured ethanol solution
      pH by the classical DPPH assay method) than at pH 5.6. Nilvadipine (CAS 75530-68
      6), a lipophilic calcium antagonist, enhanced the bleaching much more at pH 5.6
      than at pH 8.0. Nifedipine (CAS 21829-25-4) and amiodipine (amiodipine besilate,
      CAS 88150-42-9) showed some effect, but the other five calcium antagonists failed
      to bleach DPPH at any pH tested (pH 4.4-8.0). Probucol and beta-carotene
      (standard antioxidant) showed nearly the same bleaching activity as nilvadipine.
      Captopril, glutathione and bilirubin were weaker anti-free radical compounds at
      pH 5.6. No intermediating participation of superoxide radicals and hydroxyl
      radicals were observed in the DPPH assay, both at pH 8.0 and 5.6. Thus,
      nilvadipine was shown to be an efficient free-radical scavenger only at around pH
      5.6, a weak acidic condition which may occur as a result of inflammation and/or
      ischemia-reperfusion.

PMID- 11304938
TI  - Design, synthesis and antihistaminic (H1)activity of some condensed 2
      (substituted)arylaminoethylpyrimidin-4(3H)-ones.
AB  - The synthesis and potential H1 receptor antagonistic activity of two novel series
      of condensed 2-arylaminoethylpyrimidin-4(3H)-ones (4, 5) and 4-amino-2
      arylaminoethyl pyrimidines (6) have been reported. All the novel compounds were
      found to antagonize histamine in a competitive and reversible manner. When tested
      on guinea-pig ileum, compounds exhibited H1-antagonistic activity, (pA2 values)
      in the range of 8.6 to 9.7. Some of the lead compounds were evaluated by an in
      vivo method and were found to protect the guinea pigs against the histamine
      induced asphyxic shock at the doses comparable to or lower than those of the
      standard drugs, cetirizine (CAS 83881-51-0) and terfenadine (CAS 50679-08-8). The
      pA2 acetylcholine values of some of the lead compounds reflect about 1000-fold
      selectivity for histamine (H1) receptors. The 4-aminopyrimidines (6) were found
      to be more selective than their 4-one analogs (4, 5). In the radioligand binding
      study, one of the lead compounds, 6e, was found to bind reversibly at the
      histamine H1 receptor with the K1 value of 1.3 mumol/l and IC50 of 3.8 mumol/l.
      The lead compounds were found to have negligible sedative potential when tested
      in vivo. An indirect type of molecular modeling approach, using temelastine (CAS
      86181-42-2) as the standard ligand, indicates that the potent activity of 4, 5
      and 6 may be due to the increased spacer chain length between the pyrimidine
      nucleus and the side-chain aromatic ring.

PMID- 11304939
TI  - Efficacy and safety of intranasally applied dimetindene maleate solution.
      Multicenter study in children under 14 years suffering from seasonal allergic
      rhinitis.
AB  - The aim of this study was to investigate the efficacy and tolerability of
      intranasally applied dimetindene (CAS 3614-69-5) 0.1% spray in children suffering
      from seasonal allergic rhinitis. A total of 100 children under 14 years with
      acute seasonal allergic rhinitis participated in this randomised, single-blind,
      reference-controlled, multi-center, parallel group study with two treatment
      groups. The study took place between 2nd April and 16th September 1996 during the
      pollen season. Patients were examined at enrollment (day 1), day 8 and day 15.
      Patients kept diary throughout the 2-week treatment phase. Patients were
      randomised to receive either dimetindene 0.1% (Fenistil Nasal Spray) or a
      levocabastine (CAS 79516-68-0) 0.05% solution as reference medication. Both
      medications were supplied in similar outer packages. A single-blind approach was
      chosen, because the reference medication levocabastine requires two spray puffs
      per nostril as a single dose, whereas for dimetindene maleate solution a single
      spray puff per nostril is sufficient. Dimetindene 0.1% was applied with 1 spray
      puff (= 0.14 mg dimetindene) in each nostril and levocabastine with 2 spray puff
      (= 0.10 mg levocabastine) in each nostril every day in the morning before leaving
      the house and in the evening before going to bed. Additional administration of
      the spray was allowed up to 4 times a day if needed. Efficacy was assessed as
      change in severity of characteristic symptoms associated with pollen rhinitis:
      nasal rhinorrhea, nasal itching, nasal sneezing and nasal congestion. In
      addition, changes in ocular symptoms, lacrimation, ocular itching and red eyes,
      global physician's assessment of efficacy at the end of treatment were assessed.
      The primary criterion change of total nasal symptom severity score between day 1
      and day 3 resulted in a statistically equivalent and therapeutically relevant
      symptom reduction for the two treatments. All secondary criteria showed a similar
      reduction in symptoms, thus underlining the consistency of the findings. Both
      nasal sprays were well tolerated. It is concluded from these results that
      dimetindene 0.1% nasal spray solution is a safe and efficient treatment option
      for children under 14 years suffering from seasonal allergic rhinitis.

PMID- 11304940
TI  - Double-blind, placebo-controlled psychometric studies on the effects of a
      combined estrogen-progestin regimen versus estrogen alone on performance, mood
      and personality of menopausal syndrome patients.
AB  - The influence of a combined estrogen-progestin regimen (Climodien) on noopsyche,
      thymopsyche, personality and psychophysiological measures of menopausal syndrome
      patients was investigated in a double-blind, placebo-controlled, comparative,
      randomized 3-arm trial phase (Climodien 2/3 = estradiol valerate (CAS 979-32-8) 2
      mg + the progestin dienogest (CAS 65928-58-7) 3 mg = regimen A, estradiol
      valerate 2 mg = regimen EV, and placebo = regimen P) followed by an open-label
      phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg +
      dienogest 2 mg) = regimen A*. 49 women (16, 17, 16 valid patients per arm) aged
      between 46 and 67 years (mean 58, 58, 56 years, respectively) with the diagnoses
      of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1) were included in
      the analysis of the double-blind phase. Both the double-blind and the open-label
      phase lasted 2 months. Noopsychic investigations demonstrated an improvement in
      associative verbal memory after 2 months of regimen A, which was significant as
      compared with both baseline and placebo. Regarding visual memory, regimen A*
      induced an improvement, which was significantly different from the decline in
      correct reproductions in the Benton Test observed under estradiol. Errors in the
      Benton Test decreased significantly after regimen A* as compared with regimen EV.
      These findings suggest that hormone replacement therapy with estradiol, and even
      more in combination with dienogest, improves verbal and visual memory, which is
      in line with the improvement in information processing speed and capacity
      objectified by event-related potentials (ERP). Thymopsychic investigations
      demonstrated a significant improvement in somatic complaints and trait anxiety
      after both regimen A and regimen EV as compared with baseline. State anxiety
      decreased significantly under regimen A* as compared with EV. The Freiburger
      Personality Inventory showed an improvement in aggressivity after regimen A* as
      compared with the preceding placebo as well as an improvement in striving after
      dominancy after both regimen A and regimen EV as compared with pre-treatment, but
      also after regimen A* as compared with regimen EV. Extraversion increased after 2
      months of regimen A as compared to regimen P. Psychophysiological findings
      including pupillary and skin conductance variables were not significant.

PMID- 11304941
TI  - Comparative bioavailability of two oral L-thyroxine formulations after multiple
      dose administration in patients with hypothyroidism and its relation with
      therapeutic endpoints and dissolution profiles.
AB  - The aim of the present study was to evaluate the bioequivalence and therapeutic
      equivalence of the two most commonly prescribed L-thyroxine (monsodium L
      thyroxine hydrate, CAS 25416-65-3) formulations in Brazil in patients treated for
      hypothyroidism. Twenty-four patients received 100 micrograms L-thyroxine daily of
      either Puran T4 (test) or the Brazilian reference formulation (reference) during
      42 days, in a two-period crossover design. Serum samples obtained over a 24-h
      interval were analyzed for their total T4 concentration by a chemiluminescent
      immunoassay. Content and uniformity of the tablets and dissolution studies were
      also assessed according to USP 24 monograph using an isocratic HPLC-UV system and
      a rotating-paddle method. The mean pharmacokinetic parameters for total T4,
      expressed as geometric means (CV), for the test and reference were, respectively:
      Cmax (microgram/dl) 9.8 (14.3%) and 10.8 (14.9%); AUC0-24 h (microgram/dl.h)
      206.8 (13.9%) and 230.4 (14.9%). Median values (90% CI) for Tmax (h) were 3 (2-3)
      and 2 (2-4) for the test and reference, respectively. 90% CI for ratios of
      LogCmax and LogAUC0-24 h were 86.6-94.9 and 86.3-93.4, respectively. Although the
      test exhibited values of Cmax and AUC0-24 h around 10% lower than the reference,
      these formulations must be considered bioequivalent since the 90% CI for both
      Cmax and AUC0-24 h mean ratio were within the 80-125% interval as proposed by the
      US Food and Drug Administration and the Brazilian legislation. TSH dosages within
      the normal range further support therapeutic equivalence between the two
      formulations. Dissolution data were roughly in agreement with in vivo results
      since both formulations comply with the USP dissolution criteria although the
      test tablets had a slower dissolution rate than the reference tablets. As a
      conclusion, the two oral formulations of L-thyroxine are both bioequivalent and
      therapeutically equivalent although presenting a small difference in their extent
      of absorption. Noteworthy, the dissolution profiles of the tablets correlate well
      with their bioavailability in the present experimental conditions.

PMID- 11304942
TI  - Urinary metabolites of DX-8951, a novel camptothecin analog, in rats and humans.
AB  - Urinary metabolites of DX-8951 ((1S,9S)-1-amino-9-ethyl-5-fluoro- 1,2,3,9,12,15
      hexahydro-9-hydroxy-4-methyl-10H,13H- benzo[de]pyrano[3',4':6,7]indolizino[1,2
      b]quinoline-10,13-dione, CAS 171335-80-1, exatecan) in rats and humans were
      identified. Rats were dosed with the drug, and two major metabolites (UM-1 and UM
      2) in the urine were isolated and purified by using ion-exchange column and HPLC.
      From NMR and mass spectra, they are suggested to be 4-hydroxymethyl metabolite
      (UM-1) and 3-hydroxy metabolite (UM-2) of the drug. Their chemical structures
      were confirmed by comparing their NMR spectra with those of chemically
      synthesized metabolites. Two major metabolites were found in human urine obtained
      in phase I trial. They were also confirmed to be UM-1 and UM-2 by LC/MS/MS by
      comparing their mass fragment patterns with those of synthetic metabolites.

PMID- 11304943
TI  - Biodistribution and pharmacokinetics of variously sized molecular radiolabelled
      polyethyleneiminomethyl phosphonic acid as a selective bone seeker for therapy in
      the normal primate model.
AB  - An ideal radiopharmaceutical for the treatment of neoplastic and inflammatory
      (benign) bone disease would be a radiolabelled compound that predominantly
      accumulates in bone lesions with limited access to normal bone and other organs.
      Neoplastic tissue's abnormal blood supply (increased permeability) and lack of
      lymphatics will selectively accumulate radiolabelled macromolecules. This
      enhanced permeability and retention effect forms the basis of this study, using
      various molecular sizes of the radiolabelled macromolecule
      polyethyleneiminomethyl phosphonic acid (PEI-MP) for increased selectivity of the
      bone-seeking radiopharmaceutical. PEI-MP was synthesized by condensation of
      polyethyleneimine, phosphonic acid and formaldehyde, followed by fractionation
      into different molecular sizes by membrane ultrafiltration. Labelling efficiency
      to 99mTc (as radiotracer) was approximately 99% with complexes stable for 24 h.
      The pharmacokinetics and biodistribution of various 99mTc-PEI-MP fractions were
      investigated using 4 experimental baboons (Papio ursinus) per fraction.
      Scintigraphy was performed on the baboons under general anaesthesia of
      pentobarbital i.v. After an i.v. bolus of 99mTc-PEI-MP (approximately 185 MBq)
      both dynamic studies (30 x 1 min frames), and static studies (2 min acquisition
      every hour for 4 h) were done, as well as blood samples and urine collected. From
      the results macromolecules with sizes ranging between 30-300 kDa were
      characterized by excessive liver (21%-57% retained activity) and kidney (40%
      retained activity) uptake and accompanying long residing times (t1/2 up to 24 h).
      The percentage bone uptake averaged at 8% for these particles excluding sizes 100
      300 kDa where very little bone uptake was seen (< 1%). In this case the blood
      clearance was also slow (t1/2 approximately 2 h). The fraction size 10-30 kDa had
      comparatively low accumulation and short residence times in the liver and kidneys
      (resp. 20%, t1/2 = 22 +/- 4 min; 17.5%, t1/2 = 20 +/- 3 min) and although the
      bone uptake of 18% in this case was high, it is still low for a bone-seeking
      agent. These particles cleared the blood with t1/2 = 25 +/- 2 min and seemed
      suitable for labelling with a therapeutic radioisotopic agent.

PMID- 11304944
TI  - Antimicrobial activity of thiamphenicol-glycinate-acetylcysteinate and other
      drugs against Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae is responsible for respiratory tract infections of both
      upper and lower respiratory tract. Although this bacterium is one of the most
      wide-spread pathogens of man, there are limited data on the antibiotic treatment
      of C. pneumoniae infections. The aim of this study has been to evaluate the in
      vitro activity of thiamphenicol glycinate acetylcysteinate (TGA, CAS 20192-91-0)
      in comparison with molecules with established activity against C. pneumoniae, as
      well as macrolides and quinolones. The results have shown that TGA and
      clarithromycin (CAS 81103-11-9) are the most active drugs tested, but it is
      important to underline that the minimal inhibitory concentration (MIC) ranges of
      TGA are very much lower than the breakpoint of thlamphenicol for the respiratory
      pathogens. In conclusion, the good antimicrobial in vitro activity of TGA against
      C. pneumoniae together with its in vivo characteristics, in particular the high
      concentration reached in lung and the combination with the mucolytic agent N
      acetylcysteine (NAC, CAS 616-91-1), can make a valid choice in the treatment of
      respiratory tract infections caused by C. pneumoniae. These findings need further
      evaluation by clinical studies.

PMID- 11304945
TI  - [Phlebotomines of the Isle of Cyprus. III. Species inventory ].
AB  - Three surveys on canine leishmaniasis were carried out in Cyprus (1993, 1998 and
      1999) emphasise the presence of eleven species of phlebotomine sandflies:
      Phlebotomus (Phlebotomus) papatasi, P. (Paraphlebotomus) alexandri, P. (Pa.)
      jacusieli (first mention in Cyprus), P. (Pa.) sergenti, P. (Larroussius)
      galilaeus, P. (L.) tobbi, P. (Transphlebotomus) economidesi, P. (T.) mascittii,
      Sergentomyia (Sergentomyia) azizi (its specific statute is validated by the
      authors), S. (S.) fallax et S. (S.) minuta. P. (Adlerius) kyreniae was not caught
      during the surveys. The authors propose hypothesis of settlement of the island by
      phlebotomine sandflies according this species inventory. A first migration period
      took probably place during the Miocene time and a second one during the
      Pleistocene time.

PMID- 11304946
TI  - [Features of larval development in Simulium buissoni Roubaud, 1906, and S.
      sechani Craig and Fossati, 1995 (Diptera: Simuliidae) in the Marquesas
      Archipelago (French Polynesia)].
AB  - Two anthropophilic species are known from the Marquesas archipelago (French
      Polynesia): Simulium buissoni Roubaud, 1906 and S. sechani Craig & Fossati, 1995.
      The need to control them requires good knowledge about their larval growth,
      larvae being the only stage actually susceptible to control. A biometric study
      based on cephalic measures of the two species, shows that they both have seven
      larval instars. Size variations following species and sampling sites are
      examined, as are variations of the sex of the two last larval instars. A
      recolonization experiment, after treatment of a part of a river, allows us to
      quantify larval growing length of S. buissoni, which is about 12 days. These data
      allow us to determine the optimal treatment frequency.

PMID- 11304947
TI  - Chinese phlebotomine sandflies of subgenus Adlerius nitzulescu, 1931 (Diptera:
      Psychodidae) and the identity of Phlebotomus sichuanensis Leng & Yin, 1983. Part
      I--Taxonomical study and geographical distribution.
AB  - Four species of Adlerius phlebotomine sandflies have been recorded in China,
      namely: P. chinensis Newstead, 1916 (Pc), P. fengi Leng & Zhang, 1994; P.
      longiductus Parrot, 1928 and P. sichuanensis Leng & Yin, 1983 (Ps). Adlerius
      phlebotomies are the main vectors of visceral leishmaniasis (VL) in China; three
      of them are acknowledged as VL vectors and P. fengi is considered a potential VL
      vector for southwestern mountainous region. Different opinion has been raised to
      the validity of identity of Ps by some investigators from Shanghai and Shanxi who
      consider Ps to be a large type of Pc instead of an isolate species. The center of
      controversy is whether Ps is an isolate taxon or a large type of Pc. The present
      authors have carried out a series of comparative studies for these two flies on:
      1 quantitative and qualitative morphological characters of four Chinese Adlerius
      phlebotomies; and 2. differences in geographical distribution. All specimens of
      Pc and Ps used in the present study are collected where their holotypes-paratypes
      were produced--West Mountain, West Suburb, Beijing and Lixian County, Sichuan
      Province. The results have forcefully proved that Ps is an isolate species
      instead of a so-called large type Pc according to the concept of species. The
      clarification of their taxonomical identities is meaningful because both of them
      are VL vectors in different epidemic areas in China; especially Ps is an
      important VL vector in high mountainous regions of southwestern China and some
      extend to the Loess Plateau of northwestern China, where VL still exists and it
      is also the first Phlebotomine sandfly discovered in Tibet, the locality being
      near Assam in India (Leng et al. 1990).

PMID- 11304948
TI  - [Aspects of the aggressivity cycle of Simulium buissoni Roubaud, 1906 (Diptera:
      Simuliidae) in Nuku-Hiva, Marquesas Archipelago (French Polynesia)].
AB  - High density of haematophagous blackflies on Nuku-Hiva Island (Marquesas
      archipelago, French Polynesia) is a handicap to its optimal development. The
      present study contains observations from many sampling sites to examine
      aggressive periods of Simulium buissoni Roubaud, 1906. Density of aggressive
      females is very high, principally in highly irrigated sites of the island. Biting
      rates show low variation between days, and a diurnal activity, with a poorly
      pronounced circum-meridian maximum. Parity rates show great variation between
      sampling stations, but are lowest during the day. A hypothesis of greater spatial
      dispersion of nulliparous females allows explanation of much of the observed
      variation. Sampling in and out of a house shows exophily of blackflies.
      Proportion of parous females is greater in the house. Data collected over a long
      period show that earlier densities were greater than recent ones. Perturbation of
      the environment is probably the basis of this decrease.

PMID- 11304949
TI  - Syphacia longaecauda n. sp. (Nematoda: Oxyuridae) syphacinea from Melomys spp.
      (Muridae: Hydromyinae) from Papua New Guinea and Irian Jaya, Indonesia.
AB  - A new oxyurid nematode Syphacia (Syphacia) longaecauda n. sp. is described from
      the caecum and colon of the hydromyine rodents Melomys monktoni (type host) and
      M. rubex from Papua New Guinea and Irian Jaya, Indonesia. Syphacia longaecauda
      has an oval, laterally extended, relatively large cephalic plateau and can be
      distinguished from other species of Syphacia with similar characters by, amongst
      other features, tail length. The significance of the distribution of S.
      longaecauda, apparently restricted to New Guinea, is discussed.

PMID- 11304950
TI  - Gallegostrongylus australis n. sp. (Nematoda: Angiostrongylidae) from Muridae in
      Australia, with zoogeographical considerations.
AB  - Gallegostrongylus australis n. sp. (Nematoda: Angiostrongylidae) is described
      from subpleural nodules in the lungs of Rattus fuscipes, R. lutreolus and Mus
      domesticus in Australia. It is distinguished from G. andersoni occurring in
      gerbillids in West Africa by the shorter lengths of spicules and gubernaculum,
      and from G. ibicensis occurring in microtids and murids in Spain by the greater
      lengths of spicules and gubernaculum and the shorter distances from vulva and
      from anus to the caudal extremity of females. The parasite has been found only in
      16 of 4,227 (prevalence 0.38%) animals representing at least 28 species of native
      and three species of introduced murid rodents throughout Australia. The genus
      Gallegostrongylus may be an old one, possibly originating in rats. By rafting
      and/or human activities the parasite appears to have been distributed around the
      world where it has encountered suitable intermediate hosts and available niches
      for colonisation of new definitive hosts. Consequently, morphologically similar
      but biologically distinct species have evolved in rodent hosts in West Africa,
      the western Mediterranean, and Australia.

PMID- 11304951
TI  - Molineus torulosus (Nematoda, Trichostrongylina, Molineoidea) a parasite of
      Neotropical primates: new morphological and histological data.
AB  - Molineus torulosus (Molin, 1861) parasite of Cebus spp. from South America is
      redescribed in Cebus apella and C. olivecaeus (new host) from French Guyana with
      emphasis on the synlophe. During the maturation process, the larvae dwelt in the
      cysts carved alongside the external part of the small intestine. The turn-out of
      the mature worms and the laid eggs depended on the tissular organisation of cyst
      walls as the inflammatory process waned and fibrosis progressed to seal the
      cystic lumen. Adult worms entwine themselves in the cysts, live there permanently
      as their presence has never been evidenced in the intestinal lumen. They
      copulated, laid eggs, degenerated and died once entrapped by the fibrotic
      process. Laid eggs released in the intestinal lumen through a narrow channel
      ensured the continuation of the developmental cycle. However, erratic migration
      was possible via the vascular channels surrounding the cysts.

PMID- 11304952
TI  - [Sero-epidemiologic profile of toxoplasmosis in northern Tunisia].
AB  - Toxoplasma antibodies prevalence was studied in the north of Tunisia where a mild
      climate prevails. Two groups of individuals were investigated: 857 living in
      rural area and 564 living in urb town. Sera were analysed by ELISA and indirect
      immunofluorescence. The overall prevalence was 58.4%. It roses from 24.5% at ten
      years to 52.1% at 20 years of age. A maximum level, around 70%, was reached by
      about 30 years. The risk of acute infection after this age seemed low as judging
      by the proportion of high antibodies titers observed in this group (14.2% before
      30 years vs 3.7% after). A significantly higher prevalence was detected in urban
      residents (67% vs 52.8%). In this group, the rate of seroconversion seems the
      highest between ten and 20 years of age and the majority of women are infected
      before reaching childbearing age. In the rural area, the seropositivity is lower
      between ten-20 years and many women at childbearing age still susceptible to
      toxoplasmosis. The risk of acute infection seems higher in the youngest ones as
      showed by the proportion of high antibodies titers observed in the 18-30 age
      group (9.2%) compared to the one observed after 30 years (1.9%).

PMID- 11304953
TI  - Preliminary analysis of the proteolytic enzymes in the excretory-secretory
      products of the adult stages of the dog hookworm Uncinaria stenocephala.
AB  - The paper describes an introductory characterisation of proteinases present in
      the excretory-secretory products (ESP) of adult Uncinaria stenocephala. In SDS
      PAGE gelatine substrate gels ESP resolved as a six bands of proteolytic activity,
      with a molecular weight of 182, 159, 98, 50, 39 and 26 kDa. The 98 and 39 kDa
      components were serine proteinases. The 50 kDa band was sensitive to a
      metalloproteinase inhibitor. The 26 kDa component was highly sensitive to
      cysteine proteinase inhibitors and was also partially inhibited in the presence
      of EDTA. The bands of 182 and 159 kDa were sensitive to a Zn-metalloproteinase
      inhibitor. The enzymes present in ESP showed the highest proteolytic activity at
      pH 8-9. Quantitative analysis revealed maximum proteolytic activity of the
      polypeptides of 159 and 182 kDa at pH 7; 98 and 26 kDa at pH 8 while the 50 kDa
      and 39 kDa components showed the highest activity at pH 9.

PMID- 11304954
TI  - Kidney sphaerosporosis with extrasporogonic stages in the blood in Baryancistrus
      sp. (Loricaridae) from Amazonian Brazil.
AB  - Examined fish of the genus Baryancistrus (Loricaridae) from Rio Xingu in central
      amazonian Brazil were found infected with extrasporogonic stages of Sphaerospora
      sp. (Myxosporea) in the blood and sporogonic stages in the glomeruli with the
      resulting escape of the sporogony products into the renal tubules, apparently
      when the mesangial tissue in the Bowman's capsule collapsed. Spores were seen
      evacuating via the urinary tubules. Blood stages were initially 2.1 x 2.8 to 2.8
      x 2.8 microns in size, and when fully differentiated reached 5.6 x 5.6-5.6 x 7.0
      microns; in blood smears they were 11.2 x 8.4 to 14 x 8.4 microns. Bisporoblasts
      in the glomerular taft were 9.8 x 7.0 microns, premature spores were 5.6 x 4.2
      5.6 microns.

PMID- 11304955
TI  - [Pseudorascora parva (Teleostei, Cyprinidae), an invasive species, a new vector
      for the maintenance and dissemination of anguillicolosis in France?]].
AB  - Pseudorasbora parva (Pisces, Cyprinidae) is an invasive species from eastern
      Asia. Known in France since 1983, it has only been observed since 1993 in the
      Rhone delta where large populations occur. 203 specimens of that fish species
      have been examined for L3-larvae of Anguillicola crassus. 35% of the fish were
      found to be infected.

PMID- 11304956
TI  - Serum C-reactive protein and haptoglobin concentrations in patients with vivax
      malaria.

PMID- 11304957
TI  - Natural history of Plasmodium falciparum malaria and determining factors of the
      acquisition of antimalaria immunity in two endemic areas, Dielmo and Ndiop
      (Senegal).
AB  - Development of new anti malaria strategies and particularly vaccines, needs an in
      depth understanding of the relationships between transmission, infection,
      immunity, morbidity and mortality. The intensive and longitudinal collection of
      entomological, parasitological and clinical data from the Senegalese populations
      of Dielmo (250-300 inhab.), exposed to a perennial and intense transmission
      (about 200 infective bites/person/year) and of Ndiop (300-350 inhab.), exposed to
      a seasonal transmission (about 20 infective bites/person/year), allows to respond
      to many questions about this subject. The existence of a pyrogenic threshold
      effect of parasitaemia allows the individual diagnosis of malaria attacks. The
      initial intensity of clinical manifestations does not differ perceptibly among
      children and adults, is not related to the duration of the attacks, is not
      predictive of their severity, and the clearance of parasites and manifestations
      is longer among youngest persons. The risk of malaria attacks is lower as one
      gets older and among carriers of AS haemoglobin, is higher when transmission
      increases and during pregnancy up to three month after delivery, and vary between
      children. The risk of malaria attack per infective bite is negatively related to
      the intensity of transmission. Because of their high sensitivity in malaria case
      detection, this type of small community-based studies are powerful and useful for
      the identification of protective immunological mechanisms as well as for testing
      rapidly and cheaply the clinical efficacy of any intervention such as
      antimalarial vaccines and drug therapy or prophylaxis.

PMID- 11304958
TI  - [Fears in the beginning of the 21st century].

PMID- 11304959
TI  - [Role of the thymus in the pathophysiology of autoimmune diabetes type 1].
AB  - The induction of immunological self-tolerance begins in the thymus during fetal
      life. The random recombination of gene segments coding for TCR is followed by the
      negative selection of T cells bearing a TCR directed against self-antigens
      presented by thymic MHC. Insulin-like growth factor type 2 (IGF-2) is the
      dominant gene of the insulin family that is transcribed and translated in the
      thymus of different species. Contrary to the other members of the insulin gene
      family, IGF-2 gene (IGF2) is not transcribed in the thymus of diabetes-prone BB
      rats. The absence of thymic IGF2 expression is associated with the diabetogenic
      autoimmune process in BB rats. This defect could not only contribute to the
      lymphopenia of BB rats, but also to the absence of central self-tolerance of the
      insulin family in this animal.

PMID- 11304960
TI  - [European Agency for the Evaluation of Medicinal Products: five years
      experience].
AB  - The "European Agency for the Evaluation of Medicinal Products" (EMEA) is since
      1995 primarily responsible for the scientific evaluation of applications for a
      European marketing authorisation for medicinal products derived from
      biotechnology and other high technology (centralised procedure). For other
      products, the EMEA arbitrates where mutual recognition of national marketing
      authorisations between the Member States is not possible (decentralised
      procedure). European patients are now able to have speedier access to new drugs,
      usually within one year. The new system also helps to reinforce the safety of
      medicines for humans and animals, particularly through a pharmacovigilance
      network and the establishment of safe limits for residues in food-producing
      animals.

PMID- 11304961
TI  - Transverse uterine incision non-closure versus closure: an experimental study in
      sheep.
AB  - SUBJECT: This study was designed to investigate whether the non-closure of the
      layers of the uterus during low transverse cesarean section would result in
      healing and have advantage on closure. MATERIAL AND METHOD: Thirty pregnant ewes
      randomly divided into two groups. Each group included 15 ewes. Each ewe was
      anesthetized at para-vertebral region with the injection of 20 ml Prilocine 2%.
      Following left transverse abdominal incision, a transverse incision was made on
      the uterus and lambs were delivered. In the first group, uterine incision line
      was left open. In the second group, uterine incision line was sutured with no. 1
      Chromic catgut by Schimiden technique. In both groups, all layers of abdominal
      wall except skin were sutured as en-bloc with Vicryl no. 2, by continuous suture
      technique. Skin was sutured with no. 00 silk interrupted sutures. The ewes were
      slaughtered four months after cesarean section. A coworker was asked to open the
      abdominal cavities, and score the intra-abdominal adhesions. Tissues taken from
      incision line of each uterus were fixed in 10% neutral buffered-formalin and were
      embedded in paraffin-block. Sections were cut and stained with hematoxylin-eosin.
      A pathologist, who knew nothing about the study, evaluated all sections, and
      reported the findings. Student's t test was used for comparison of mean ewe age,
      gestational age, and mean operation time of the two groups. Z test was used for
      comparing the ratio of the two groups by means of histopathological findings.
      RESULTS: No cervical dilatation and delivery of the placenta were seen during the
      four week follow up period. The average operating time was significantly less for
      the non-closure group (48.07 +/- 3.83 minutes) than for the closure group (62.53
      +/- 6.57 minutes; p = 0.001). The ranges of myometrial necrosis (100% versus
      13.3%; p = 0.001) and endometriosis (53.3% versus 00.0%; p = 0.001) were
      significantly higher for closure group than for non-closure group. CONCLUSION: It
      was found that non-closure layers of the uterus along low transverse cesarean
      incision proves to have no adverse effect on immediate and late postoperative
      period in ewes. Our data showed that non-closure of all layers of the uterus
      results in significantly less muscular necrosis and endometriosis than closure
      group. We suggest that lower uterine incision can be left unclosed or, at least,
      simple closure can be preferable instead of vigorous locking technique.

PMID- 11304962
TI  - Relation between viability of vaginal polymorphonuclear leukocytes and presence
      of histologic chorioamnionitis.
AB  - BACKGROUND: The number and percentage of viable vaginal polymorphonuclear
      leukocytes (vPMNs) are known to be increased in women who experience preterm
      labor. Whether those parameters may be associated with the presence of histologic
      chorioamnionitis (CAM) is not known. METHODS: We investigated prospectively 39
      women at 26.3 +/- 6.2 weeks of gestation. The following were determined in
      vaginal washings: total number of vPMNs and the percent that were viable, the pH,
      and the concentrations of granulocyte elastase and interleukin-8 (IL-8). In
      addition, the white blood cell count and the serum level of C-reactive protein
      were determined in peripheral blood. The placenta and the umbilical cord were
      examined histologically with special reference to the presence of CAM. The
      optimal cutoff value for prediction of histologic CAM was obtained for each
      variable using receiver operating characteristic curves. A multivariate logistic
      regression model was used to determine the independent risk factors for this
      disorder. RESULTS: Histologic CAM was present in ten women (37.1 +/- 3.8 weeks)
      and absent in 29 women (38.2 +/- 1.5 weeks). The total number of vPMNs, the
      percent of viable vPMNs, and the IL-8 level were all significantly increased in
      the women with CAM, in contrast to those without CAM. When the optimal cutoff
      value for each of seven covariates was entered into the model, only the percent
      of viable vPMNs, > or = 11%, demonstrated a significant relationship with
      histologic CAM (odds ratio 26.9; 95% confidence interval 1.3 to 545; p < 0.05).
      CONCLUSIONS: Women with a % viability of vPMNs of > or = 11% were at a
      significantly higher risk for histologic CAM. Data suggest that an influx of PMNs
      into the vagina occurs continuously in patients with histologic CAM.

PMID- 11304963
TI  - Seroprevalence of Toxoplasma gondii among pregnant women in Sweden.
AB  - BACKGROUND: Primary infection with Toxoplasma gondii during pregnancy can cause
      fetal infection with a risk of complications for the fetus. The proportion of
      women at risk of acquiring the infection during pregnancy in Sweden is not known.
      METHODS: The seroprevalence of Toxoplasma gondii among pregnant women in Sweden
      was calculated when 40,978 blood samples collected on filter paper eluates from
      newborns were tested for Toxoplasma specific immunoglobulin G. The newborns in
      two geographically different areas (Stockholm County and Skane County) were
      investigated during a 16-month period between April 1997 and July 1998. The anti
      toxoplasma IgG antibodies detected in the eluates were considered to be of
      maternal origin and to reflect the immune status of the mother. RESULTS: The
      seroprevalence was 14.0% in Stockholm County and 25.7% in Skane County. The
      seroprevalence among women born in the Nordic countries was 11.1% in Stockholm
      and 24.9% in Skane. The corresponding figures for women born outside the Nordic
      countries were 24.3% and 29.4%. On comparing the seroprevalence found in this
      study with older data, the overall seroprevalence in pregnant women born in the
      Nordic countries and living in Stockholm was found to have decreased between 1969
      and 1998. The seroprevalence in different birth cohorts, longitudinally followed
      in the previous and the present studies, remained at the same level over 20 years
      despite the increasing age of the women. CONCLUSION: These results suggest that
      the majority of seropositive pregnant women in Sweden today have seroconverted
      before entering the childbearing period and that the percentage of women in
      Sweden acquiring toxoplasmosis during the childbearing period is low.

PMID- 11304964
TI  - Factors affecting the volume of umbilical cord blood collections.
AB  - OBJECTIVE: Our purpose was to find factors that may help increase the number of
      the HSC (CD34+) collected from umbilical cord blood for transplantation. STUDY
      DESIGN: We assessed the effect of cesarean sections and vaginal deliveries on the
      volume of the umbilical cord blood collected from 155 healthy term neonates
      retrospectively. RESULTS: The volume of umbilical cord blood obtained in 29
      cesarean deliveries was 103.9 +/- 33.6 ml compared with 84.2 +/- 25.3 ml
      collected in 126 vaginal deliveries. Although the percentage of CD34+ cells was
      comparable in both groups, the absolute number of CD34+ cells was significantly
      higher in the cesarean section group because of the larger volume collected.
      CONCLUSIONS: Cesarean sections may allow collection of significantly increased
      volumes of umbilical cord blood and numbers of CD34+ cells compared to vaginal
      deliveries.

PMID- 11304965
TI  - Perinatal deaths in the Faroe Islands during 1986-95.
AB  - OBJECTIVE: To examine causes of perinatal mortality in the Faroe Islands, where
      it has been increased compared to other Nordic societies. METHOD: Cases were
      classified according to a fetal/obstetric, a fetal/neonatal, and a
      fetal/obstetric/neonatal classification (classifications C1, C2, and C3,
      respectively). SETTING: The Faroe Islands 1986-1995; as reference materials were
      used a) the preceding decade in the Faroes and b) a parallel period in Denmark.
      SUBJECTS: We examined all available information regarding each case from hospital
      records, midwife records, birth certificates, death certificates and autopsy
      records. RESULTS: The perinatal mortality was 10.3 per 1,000 total births
      (83/8,096) compared with 13.7 (102/7,458) in the preceding decade; the fall could
      be attributed to fewer cases with preeclampsia, antepartum bleedings (C1) and
      antepartum asphyxia (C2) and the number fell despite an increased occurrence of
      cases attributed to congenital malformations. Perinatal mortality in Denmark was
      8.3 (4,574/550,971), where rates were lower of cases with congenital
      malformations and fetoplacental dysfunction, but where the rate was higher of
      cases related to preterm birth (C3). CONCLUSIONS: Although the perinatal
      mortality rate still is higher in the Faroes than Denmark, the rate had fallen in
      the Faroes from 1976-85 to 1986-1995. The fall was mainly due to fewer cases
      attributable to antepartum asphyxia, preeclampsia, antepartum bleedings, and
      hyaline membrane disease, a pattern compatible with a more efficient perinatal
      service in the Faroes in the latter period.

PMID- 11304966
TI  - Sex hormone-binding globulin in gestational diabetes.
AB  - BACKGROUND: Insulin is an important regulator of serum sex hormone-binding
      globulin (SHBG) concentration which works by inhibiting its production in
      hepatocytes. Low SHBG level is associated with increased insulin resistance and
      hyperinsulinemia. Our purpose was to compare maternal serum SHBG level between
      normal and gestational diabetic pregnant women and to study the relationships
      between SHBG, SHBG/insulin and SHBG/glucose ratio and several endocrine,
      metabolic and clinical parameters. METHODS: Serum SHBG concentrations were
      measured in 34 women with gestational diabetes and in 32 matched controls.
      Glucose, insulin, C-peptide, fructosamine, beta-HCG, cholesterol, triglycerides,
      HDL cholesterol, LDL cholesterol, apolipoprotein A, apolipoprotein B, total and
      free T4, total and free estriol, T3 and IGF-1 were measured. Insulin sensitivity
      was estimated using the short insulin tolerance test. RESULTS: SHBG,
      SHBG/insulinemia ratio and SHBG/glucose ratio were significantly lower in the
      diabetic group (309.54 +/- 112.22 vs 460.54 +/- 144.54, p = 0.00001), (33.55 +/-
      16.62 vs 72.56 +/- 66.50, p = 0.0006 using log-transformed values), (5.88 +/-
      1.87 vs 3.39 +/- 1.23, p < 0.00001). SHBG was negatively correlated with
      insulinemia (r = -0.40, p = 0.001), C-peptide (r = -0.41, p = 0.001), glycemia (r
      = -0.27, p = 0.02), diastolic blood pressure (r = -0.41, p = 0.001) and beta-HCG
      (r = -0.41, p = 0.001) and positively correlated with LDL-c (r = 0.25, p = 0.04)
      and apolipoprotein B (r = 0.33, p = 0.007). CONCLUSIONS: SHBG concentrations are
      lower in gestational diabetic pregnant women and are related to insulin levels
      but not to peripheral insulin sensitivity. Since insulinemia was similar in
      normal and gestational diabetic pregnant women, we speculate that gestational
      diabetes is characterized by a higher peripheral insulin resistance, a fasting
      normal insulinemia and a higher hepatic insulin sensitivity, at least in other
      actions than on carbohydrate metabolism. The role of sex steroids, T4 and IGF-1
      in regulating SHBG appears to be limited during pregnancy.

PMID- 11304967
TI  - Course and outcome of obstetric patients in a general intensive care unit.
AB  - BACKGROUND: To characterize the course, interventions required to achieve
      predetermined end-points and outcome of obstetric patients admitted to a general
      intensive care unit. METHODS: A retrospective case series study was performed
      including all pregnant patients admitted to an 8-bed general intensive care unit
      at a tertiary care university-affiliated hospital over a 4-year period. All
      patients referred by the obstetricians were admitted. Patients were divided into
      two groups: group 1, (n = 19) those requiring mechanical ventilatory support and
      group 2, (n = 27) those requiring intensive monitoring. Data collected included
      demographics, reason for admission, admission diagnosis, Acute Physiology and
      Chronic Health Evaluation (APACHE II) and Therapeutic Intervention Scoring System
      (TISS) scores, intensive care unit course, types of interventions used and
      outcome. End-points of therapy included systolic blood pressure 110-150 mmHg,
      urine output > or = 1 cc/kg/h and oxygen saturation > 95%. RESULTS: Over the
      study period, 46 obstetric patients were admitted to the intensive care unit,
      representing 0.2% of all deliveries and an intensive care unit utilization rate
      of 2.3%. Commonest admission diagnoses were pregnancy-induced hypertension and
      hemorrhage. Reason for admission was mechanical ventilation in 41% while 59% were
      admitted for monitoring. Median length of stay was 25 +/- 80.9 (mean 48.8) hours.
      The median APACHE II score was 6 +/- 3.9 (mean 7.24) and the TISS score was > 20
      in both groups. Only one patient died (mortality rate 2.3%). CONCLUSION: Despite
      a short length of stay and low APACHE score, the high TISS score in obstetric
      patients admitted for both ventilation and monitoring suggests that these
      patients require a level of intervention and care typically provided by a general
      intensive care unit.

PMID- 11304968
TI  - Cervical length assessment in twin pregnancies using transvaginal ultrasound.

PMID- 11304969
TI  - Risk assessment at the end of pregnancy is a poor predictor for complications at
      delivery.
AB  - OBJECTIVE: To evaluate the usefulness of prenatal risk assessment for prediction
      of need for obstetric interventions. DESIGN: Area based retrospective study.
      SETTING: Vasteras Central Hospital, Sweden, with all antenatal care units in the
      area. SUBJECTS: All women delivered at the only delivery ward in the area, after
      attending antenatal care at the affiliated ANC-units in 1990 (n = 2008) and 1992
      (n = 1874). MAIN OUTCOME MEASURES: Obstetric interventions at delivery. RESULTS:
      During the two years 81% and 83% of the study population delivered an infant in
      vertex presentation at term but 15% and 17% without risk factors or complications
      at the end of pregnancy had complications during delivery. The relative risk for
      interventions when risk factors were present was 2.2 and with spontaneous onset
      of labor 1.3/1.4. Low risk primiparae had unforeseen complications in 25% and
      multiparae in 10%. Relative risk for multiparae with risk factors and spontaneous
      labor was 2.2/1.8 and for primiparae 1.4/1.6. CONCLUSIONS: Individual prediction
      of obstetric emergencies has low accuracy, which should be included in the
      information to women as well as in discussions with health pianners.

PMID- 11304970
TI  - Influence of chorioamnionitis on survival and morbidity in singletons live-born
      at < 32 weeks of gestation.
AB  - BACKGROUND: Chorioamnionitis (CAM) may accelerate lung maturation in fetuses. It
      is possible that CAM prevents infant death after live birth. METHODS: A
      retrospective study of live-born singletons at < 32 weeks of gestation between
      1993 and 1997. Perinatal risk factors for adverse outcomes were analyzed using a
      logistic regression model, with special reference to the presence of
      histologically confirmed CAM. Adverse outcomes included infant death before 1
      year of age, and survival with cerebral palsy and/or mental retardation. RESULTS:
      A total of 81 infants, weighing 1181 +/- 426 g, were born at 28.1 +/- 2.3 weeks
      of gestation. Of those, 15 (19%) died before 1 year of age, while 16 (20%)
      infants developed major handicaps by 1.5 years of age (six with cerebral palsy,
      eight with mental retardation, and two with both cerebral palsy and mental
      retardation). CAM, present in 44 women, was significantly associated with a
      reduced risk of death after live birth, with an odds ratio of 0.11 (p = 0.01).
      Only the presence of such intracranial lesions as periventricular leukomalacia
      and intraventricular hemorrhage were significantly associated with an increased
      risk of major handicaps (odds ratio of 11.0, p = 0.04). Adverse outcomes occurred
      in a similar proportion of infants in groups without CAM (14/37) and with CAM
      (17/44). However, among infants with adverse outcomes, the number of deaths was
      significantly higher in the group without CAM (10/14) vs. with CAM (5/12) (p <
      0.05). CONCLUSIONS: The presence of CAM may somehow prevent infant death after
      live birth. Larger studies are required to confirm this phenomenon.

PMID- 11304971
TI  - Clinical outcome and tissue trauma after laparoscopic and abdominal hysterectomy:
      a randomized controlled study.
AB  - BACKGROUND: To evaluate clinical outcome and tissue trauma after laparoscopic and
      abdominal hysterectomy. METHODS: Fifty women scheduled for abdominal hysterectomy
      were randomized to undergo either laparoscopic (n = 25) or abdominal (n = 25)
      hysterectomy. Surgical characteristics, hospital stay, convalescence and
      complications were analyzed. Blood samples for assay of markers of tissue trauma
      (interleukin-6, C-reactive protein, tumor-associated trypsin inhibitor and tumor
      associated antigen CA 125) were taken preoperatively, on the first, second and
      seventh postoperative day and at the follow-up visit four weeks after surgery.
      RESULTS: In uncomplicated hysterectomies (n = 18) the operating time (85.3 min
      versus 57.5 min, p < 0.00001) was longer for laparoscopic group but the hospital
      stay (2.1 days versus 3.4 days, p < 0.00001) and sick leave (21.4 days versus
      38.5 days, p < 0.00001) were shorter in the laparoscopic group. Postoperative
      increases in all markers were significant in both groups. The interleukin-6
      concentration was highest on the first postoperative day in both groups, that of
      C-reactive protein on the second postoperative day in both groups, tumor
      associated trypsin inhibitor on the seventh postoperative day in the laparoscopic
      group and on the second postoperative day in the abdominal group and tumor
      associated antigen CA 125 on the seventh postoperative day in both groups. Both
      interleukin-6 and C-reactive protein levels were lower in the laparoscopic group
      on the first (p = 0.01 and p = 0.03, respectively) and on the second
      postoperative day (p = 0.02 and p < 0.001, respectively) compared with the
      abdominal group. No differences were seen in tumor-associated trypsin inhibitor
      and tumor-associated antigen CA 125 levels between the groups. CONCLUSION:
      Laparoscopic hysterectomy should replace abdominal hysterectomy whenever possible
      because of a more favorable clinical outcome and less tissue trauma.

PMID- 11304972
TI  - Vulvar vestibulitis: medical, psychosexual and psychosocial aspects, a case
      control study.
AB  - BACKGROUND: Vulvar vestibulitis is suspected to be increasingly prevalent among
      young women, but the etiology is still unclear. The aim of this study was to
      explore the differences in medical, psychosexual and psychosocial factors between
      women with vulvar vestibulitis and a control group. METHODS: A case-control study
      was made with 38 women with vulvar vestibulitis and 71 healthy age-matched
      controls. All the women answered a structured questionnaire about their medical
      and gynecological history which included psychosexual and psychosocial background
      factors and current aspects as well. RESULTS: Women with vulvar vestibulitis have
      very much the same psychosocial and sexual background factors as their controls,
      whereas there are many differences in their medical background factors, both
      gynecological and others. It is very clear that they suffer from many other
      somatic symptoms more often than their controls. CONCLUSIONS: There are no
      indications of a primary sexual disturbance in women with vulvar vestibulitis.
      However, the finding that women with vulvar vestibulitis have many different
      somatic symptoms indicates a psychosomatic strain in the illness. Regardless of
      whether this is primary or secondary, it should be taken into consideration when
      treating the patients.

PMID- 11304973
TI  - Medium-term follow-up of women with menorrhagia treated by rollerball endometrial
      ablation.
AB  - BACKGROUND: To assess medium-term efficacy of rollerball endometrial ablation in
      a district general hospital. METHOD: From March 1992 to June 1997, 91 women
      underwent rollerball endometrial ablation for uncontrolled menorrhagia
      unresponsive to medical treatment. Each was sent a detailed questionnaire after
      at least 18 months (range 18-55). There was an overall response rate of 88%
      (80/91). Case notes were reviewed to collect additional data related to pre
      operative management and actual operative procedure. The main outcome measures
      included treatment satisfaction, relief of symptoms, improvement in health
      related quality of life, at least 18 months after surgery. RESULTS: Thirty-five
      of the 80 women (44%) had achieved amenorrhea. Ten women required further
      treatment; of these seven had a hysterectomy (9%). None of the non-responders had
      a hysterectomy. Following rollerball endometrial ablation, many women reported
      improvement in cyclical pelvic pain (73%), pre-menstrual symptoms (65%), ability
      to do housework (85%), and an improved sexual life (96%). Seventy-nine (99%)
      women were able to return to normal work within 4 weeks following surgery. The
      majority of them remained satisfied with treatment (79%) and they would recommend
      it to a friend (91%). CONCLUSIONS: Rollerball endometrial ablation is a simple,
      effective, and acceptable procedure for the treatment of menorrhagia in selected
      cases. Longer-term follow up is still needed to establish the ultimate
      effectiveness of the procedure.

PMID- 11304974
TI  - Hepatic hematomas in pregnancy.

PMID- 11304975
TI  - Postpartum hematoma and vaginal packing with a blood pressure cuff.

PMID- 11304976
TI  - A seminoma case which occurred in a patient with familial testicular feminization
      syndrome.

PMID- 11304977
TI  - Clear cell carcinoma presenting as a pedenculated cyst encapsulated by uterine
      smooth muscle tissue.

PMID- 11304978
TI  - Lymphangioma of the ovary.

PMID- 11304979
TI  - Pregnancy with unilateral lung agenesis.

PMID- 11304980
TI  - Near-fatal paradoxical gas embolism during gynecological laparoscopy.

PMID- 11304981
TI  - Uterine conservation in patient with consecutive double placenta percreta.

PMID- 11304982
TI  - Endometrial polyps during menopause: characterization and significance.

PMID- 11304983
TI  - [Changes of infections due to drug resistant bacteria and its control].
AB  - The development and use of antibiotics for the chemotherapy of bacterial
      infections was one of the most remarkable accomplishments in medicine of the
      20th. However, antibiotic-resistant bacteria were found in clinical isolates soon
      after the introduction of the earliest antimicrobial agents into the market.
      Significant increases in prevalence of resistance to antimicrobial agents have
      been observed in common pathogens of humans in the worldwide and problems of
      resistance are still presently serious among the immunocompromised host. The most
      important of these organisms are methicillin-resistant Staphylococcus aureus
      penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus,
      and certain gram-negative bacilli due to extended-spectrum beta-lactamase
      production. These antibiotic resistances have made antimicrobial therapy of many
      infections extremely difficult or virtually impossible in some instances. In this
      article, we reviewed the history of antibiotic-resistance and discussed on the
      future.

PMID- 11304984
TI  - [Present situation of drug resistance and future prospects].
AB  - Antibiotic resistance has evolved over 60 years from a merely microbiological
      curiosity to a serious medical problem in hospitals. Resistance has been reported
      in almost all species of bacteria to various classes of antimicrobial agents
      including recently evaluated ones. Bacteria regulated resistance by different
      mechanisms. Inappropriate use of an antimicrobial agent selects resistant strains
      much more frequently. Since it is not expected that some epoch-making new
      antimicrobial agents will be developed in the near future, proper use of existing
      antimicrobial agents which is based on the mechanisms of action of antimicrobial
      agents and of resistance of bacteria, and of control of nosocomial infection are
      very important to reduce the further spread of resistant bacteria. With the
      search for natural sources of new antimicrobial substances now appearing
      frustrated, the genomic approach in the 21st century may be the only fruitful way
      to develop truly novel chemotherapeutic agents against bacterial diseases.

PMID- 11304985
TI  - [Surveillance system for nosocomial infections due to drug-resistant organisms in
      Japan and other countries].
AB  - The national nosocomial infection surveillance systems in Japan as well as
      American-European countries were overlooked. The NNIS/CDC system, which started
      in 1970, is the only continuous surveillance system focusing on the improvement
      of prevention of nosocomial infection in US. Other surveillance systems being
      started in 1980's in European countries were prevalence studies, most of which
      studied prevalence of nosocomial infections and audited drug-resistance
      organisms. The Japanese nosocomial infection surveillance system, which started
      in 2000 by Ministry of Health and Welfare, is attempting to promote system
      improvement of prevention of nosocomial infection where a risk-adjusted outcome
      was used as an evaluation criteria.

PMID- 11304986
TI  - [Molecular biology of the mechanism of acquisition of antimicrobial-resistance].
AB  - There are two ways for a bacterium to acquire antimicrobial-resistance: 1)
      Horizontal transfer of resistance gene(s) from outside, 2) Mutation of its own
      chromosome. The former case includes conjugation, transduction and
      transformation. Resistance genes usually locate on transposon or integron and
      have inverted or direct repeats on both sides, or link to a special sequence at
      one side. A target of an antibiotic is an essential enzyme for the bacterium to
      survive, and the corresponding gene is located on the chromosome. The mutation of
      the essential gene may cause resistance to antimicrobials by decreasing the
      affinity of enzyme to the drug. The mutation of genes for drug influx or efflux
      also causes antimicrobial resistance.

PMID- 11304987
TI  - [Mechanisms of methicillin and vancomycin resistance in Staphylococcus aureus].
AB  - The mechanism of methicillin and vancomycin resistance in Staphylococcus aureus
      (MRSA) is discussed, focusing on the phenotypic expression of resistance; i.e.,
      pre-methicillin resistance, Egle-type resistance, heterogeneous and homogeneous
      resistance. Acquisition of staphylococcus cassette chromosome(SCCmec) by a
      recipient MSSA strain in the mecA-positive, and methicillin-susceptible
      status(pre-MRSA status) of S. aureus. Subsequent of the mecI-gene-mediated
      repression of mecA gene transcription results in the heterogeneous expression of
      methicillin resistance. It is only with the alternation of another chromosomal
      locus that the heterogeneous-to-homogeneous (hetero-to-homo) conversion of
      methicillin resistance occurs. Acquisition of a part of vancomycin-resistance(the
      level of hetero-VRSA) is associated with hetero-to-homo conversion of methicillin
      resistance, and full expression of vancomycin resistance(MIC = 8 mg/l) is
      achieved by additional acceleration of cell-wall synthesis causing apparent cell
      wall thickening.

PMID- 11304988
TI  - [Vancomycin-resistant enterococci(VRE)].
AB  - The incidence of Enterococcal nosocomial infection has increased since 1980s.
      Most Enterococci are intrinsically resistant to many kinds of antibiotics,
      therefore, therapeutic drugs for enterococal infectious disease are limited to a
      few antibiotics such as ampicillin, gentamicin and vancomycin. However, since the
      first report of penicillinase producing E. faecalis in 1983, ampicillin-resistant
      strains have been increasing, furthermore, these strains often associated with
      high-level resistance to aminoglycosides. The yearly usage of vancomycin
      increased because vancomycin was only effective drug against such resistant
      strains and worldwide spread of multidrug-resistant MRSA which vancomycin is only
      effective. However, High-level vancomycin-resistance strains of E. faecium were
      first isolated in England in 1986. In 1990s, VRE have been spreading all over the
      world, especially, the emergency of multidrug-resistant strains, which are
      resistant to high concentrations of ampicillin or gentamicin or to vancomycin in
      USA, brought serious therapeutic dilemmas. This review focuses on the background
      in emergence of VRE, the relation with use of avoparcin, is used for growth
      promotion in farm animals, the mechanism of resistance, and the prevention of the
      spread of vancomycin resistance.

PMID- 11304989
TI  - [Beta-lactam and macrolide resistance in Streptococcus pneumoniae].
AB  - The resistance of beta-lactam antibiotics in penicillin-resistant Streptococcus
      pneumoniae (PRSP) is due to alterations in penicillin-binding proteins(PBPs).
      Recently, highly beta-lactam-resistant strains(MIC: > or = 4 micrograms/ml for
      penicillin, > or = 8 micrograms/ml for ampicillin, and > or = 4 micrograms/ml for
      cefotaxime) have been isolated. High resistance of these strains is caused by
      further alterations in pbp2x and pbp2b genes adjacent to conserved amino acid
      motifs, in addition to that detected in common PRSP. The resistant mechanisms of
      macrolides in S. pneumoniae is recognized as production of a 23s rRNA methylase
      encoded by ermB and efflux system mediated by mefA gene. We detected these genes
      by PCR in clinical isolates, and showed the relationship between the presence of
      each gene and the susceptibilities of 14-, 15-, 16-membered macrolides.

PMID- 11304990
TI  - [Beta-lactamase negative ampicillin-resistant Haemophilus influenzae(BLNAR)].
AB  - The affinity of [3H]-benzylpenicillin for penicillin-binding protein(PBP) 3A/3B
      was reduced in clinical isolates beta-lactamase-negative ampicillin(ABPC)
      resistant Haemophilus influenzae(BLNAR) with MIC of > or = 1 microgram/ml to
      ABPC. The sequence of ftsI gene encoding the transpeptidase domain of PBP3A/3B
      were determined for these strains, and compared to those of ABPC-susceptible Rd
      strain. Common substitutions of deduced amino acid residues were identified in
      transpeptidase region on the ftsI gene in BLNAR strains. Homology modeling of the
      three-dimensional structure of PBP3 showed that every common substitution
      occurred at active site pocket surrounded by three conserved motifs. The MICs of
      beta-lactams for H. influenzae transformants in which ftsI gene from BLNAR was
      introduced, were as high as those for the donors and PBP3A/3B showed a decreased
      affinity for beta-lactams. These data indicate that mutations in the ftsI gene
      are the most important for development of resistance to beta-lactams in BLNAR.

PMID- 11304991
TI  - [Extended-spectrum beta-lactamases (ESBLs) producing bacteria].
AB  - TEM- or SHV-type extended-spectrum beta-lactamases(ESBLs) are of clinical concern
      in Europe and the United States, whereas bacterial strains producing such types
      of ESBLs had not been reported in Japan for many years. Toho-1, a different type
      class A ESBL, has been reported in 1995, in which any prototypical enzyme has not
      been identified so far. At present Toho-1 is the major ESBL in Japan, however,
      SHV5 alpha has been reported in 1998, followed by TEM-26, SHV-2, and SHV12. More
      recently, SHV-24, a novel SHV-derived ESBL has also been found. Since Toho-1-type
      ESBL, AmpC-type beta-lactamase, and class B metallo-beta-lactamase have been
      widely found in Japan, a novel detection system for ESBLs suitable for this
      country should be developed.

PMID- 11304992
TI  - [Metallo-beta-lactamase producing bacteria].
AB  - Metallo-beta-lactamases are the carbapenemases belonging to the class B beta
      lactamases on a molecular level. Two types of the metallo-beta-lactamase, IMP-1
      and VIM-1, which have been detected mainly from Pseudomonas aeruginosa,
      respectively, in Japan and in Europe are especially important, because of the
      broad substrate specificity. These enzymes confer resistance to not only the
      carbapenems but also almost all beta-lactam antibiotics expect for monobactams.
      Clinical strains producing IMP-1 type enzymes are easily detectable by the PCR
      method or by the double-disk method using the enzyme inhibitor of mercapto
      compound and the substrate antibiotic such as imipenem or ceftazidime. The gene
      blaIMP is frequently identified as a cassette inserted in the integron structure
      on the transmissible plasmids, disseminating among various gram-negative
      bacteria.

PMID- 11304993
TI  - [AmpC beta-lactamases producing bacteria].
AB  - beta-Lactamases are the principal mechanism of bacterial resistance to beta
      lactam antibiotics. In recent years, resistance due to production of beta
      lactamases including extended-spectrum beta-lactamses, carbapeneases and AmpC
      beta-lactamses, has risen at alarming rate in clinical isolates of gram-negative
      bacteria. AmpC beta-lactamses are classified by whether genes locate on
      chromosome or plasmid. The purpose of this paper is to address the general
      mechanism involve in AmpC beta-lactamase production and the clinical importance
      of the enzymes.

PMID- 11304994
TI  - [Antibiotic resistance caused by membrane impermeability and multidrug efflux
      systems].
AB  - Multiple antibiotic resistance(MDR) in bacteria was at first thought to be caused
      exclusively by the combination of several resistance mechanisms including
      membrane impermeability, the outer membrane barrier in gram-negative bacteria.
      More recently, it became clear that MDR are often achieved by interplay between
      impermeability and multidrug efflux pumps. Streptococcus pneumoniae MefA,
      Staphylococcus aureus NorA and Pseudomonas aeruginosa Mex of these pumps are
      significant, because those bacteria are more frequently isolated in clinical. In
      this review, we described on characteristics and clinical significance of P.
      aeruginosa Mex systems, MexA-MexB-OprM, MexC-MexD-OprJ, MexE-MexF-OprN and MexX
      MexY-OprM, and furthermore, on interplay between the efflux systems, the outer
      membrane barrier, hydrolyzing enzyme and mutated target.

PMID- 11304995
TI  - [Multiple drug resistance of Mycobacterium tuberculosis].
AB  - Mycobacterium tuberculosis acquires drug resistance by chromosomal mutation
      resulting in alterations of target molecules of drugs.

PMID- 11304996
TI  - [Mupirocin resistant MRSA in Japan].
AB  - Mupirocin is a unique antibiotic that is produced by Pseudomonas fluorescens, and
      is available for elimination of nasal carriage of methicillin-resistant
      Staphylococcus aureus (MRSA). However, there have been many reports that high
      level mupirocin resistant S. aureus were discovered in Europe, South or North
      American countries. In Japan, mupirocin has been only available for nasal
      ointment of MRSA eradication since 1996. After introduction of mupirocin, we have
      screened mupirocin resistance routinely in our hospital. On January 1998, we had
      high level mupirocin-resistant MRSA isolated from a nose of a neonate with severe
      nephrotic syndrome. The mupA was detected by PCR and the mupirocin-resistance
      could transfer to S. aureus RN2677 by filter-mating with co-transfer of
      gentamicin, tobramycin, kanamycin and erythromycin. This strain was eradicated
      after prophylactic use of vancomycin for her nephrectomy. To our knowledge, this
      is the first isolate of high level mupirocin-resistant MRSA in Japan.

PMID- 11304997
TI  - [Clinical relevance of hetero-VRSA in surgical infections].
AB  - Vancomycin was used increasingly for treating methicillin-resistant
      Staphylococcus aureus(MRSA) infection. Recently MRSA strains which showed low
      level resistance to vancomycin were isolated. Vancomycin-intermediate
      Staphylococcus aureus(VISA) show a vancomycin minimum inhibitory
      concentration(MIC) of 8 micrograms/ml. VISA appear to be rare. The vancomycin
      resistance phenotype is reported to be unstable in such isolates. To detect
      heterogeneously resistant VRSA(hetero-VRSA. MIC 1 to 4 micrograms/ml), we need to
      use population analysis and growth on Mu3 agar plate, because MIC cannot confirm
      hetero-VRSA. Hetero-VRSA is not so rare(about 0-47%). Hetero-VRSA may be
      responsible for failure of vancomycin therapy, but its mechanism remains unclear.
      Until it becomes better understood, the clinical relevance cannot be assessed.

PMID- 11304998
TI  - [Combination therapy against vancomycin-resistant enterococci].
AB  - The therapeutic options for patients infected with vancomycin-resistant
      enterococci are limited. Optimal therapy for serious enterococcal infections
      requires the use of synergistic combinations of a cell wall-active agent plus an
      aminoglycoside. Enterococci have acquired aminoglycoside resistance genes that
      mediate production of aminoglycoside-modifying enzymes, which eliminate this
      synergistic bactericidal effect. Traditional therapy has been compromised due to
      the increasing prevalence of enterococci with beta-lactam, glycopeptide, and high
      level gentamicin resistance. Arbekacin, a semi-synthetic aminoglycoside, shows
      excellent activity against a wide variety of bacteria that produce aminoglycoside
      modifying enzymes, including AAC(6')-APH(2"). In recent studies, the combination
      of ampicillin and arbekacin demonstrated inhibitory activity against vancomycin
      resistant enterococci, and may prove useful in the treatment of enterococcal
      infections where treatment options are limited.

PMID- 11304999
TI  - [The latest trend of PRSP infection].
AB  - Streptococcus pneumoniae is an important pathogen and is a leading cause of
      pneumonia, meningitis, otitis media and sinusitis. Penicillin-resistant
      Streptococcus pneumoniae(PRSP) first appeared in the 1970s, and its has been
      increasing recently worldwide. Penicillin resistance among streptococcal isolates
      has been rapidly emerged in Japan the last decade, too. Penicillin and beta
      lactam resistance due to altered penicillin binding protein was recognized.
      Resistant strains to other non-beta-lactam drugs, such as the macrolides,
      clindamycin, minocycline began to increase. Despite the use of appropriate
      antimicrobial agents, therapeutic failure in-patients with pneumococcal infection
      were increasing. It will be more important to select antimicrobial agent for PRSP
      infection, especially in meningitis, where the minimum inhibitory concentration
      of drug in cerebrospinal fluid may be less than the MIC in the blood. In the
      future 23-valent pneumococcal capsular polysaccharide vaccine should be used all
      persons 2 years of age and older who are at risk for serious pneumococcal disease
      and in all persons 65 years of age and older.

PMID- 11305000
TI  - [Clinical characteristics of beta-lactamase negative ampicillin resistant
      Haemophilus influenzae (BLNAR) in respiratory tract].

PMID- 11305001
TI  - [Clinical characteristics of emerging multiple-drug-resistant gram-negative rods
      producing extended-spectrum beta-lactamases (ESBLs)].
AB  - The prevalence of organisms producing extended-spectrum beta-lactamases(ESBLs)
      has been increasing all over the world. ESBLs confer resistance to cefotaxime,
      ceftazidime, aztreonam, extended-spectrum penicillins, and structurally related
      beta-lactams in clinical isolates of K. pneumoniae and E. coli. Under the
      influence of antimicrobial agents, bacteria that primarily produce TEM-type or
      SHV-type beta-lactamases developed point mutations in structural genes which
      served to extend the substrate specificity of the enzymes. Infections caused by
      ESBLs producing isolates are difficult to detect with current susceptibility
      tests, and are difficult to treat. This article provides an historical overview
      of the emergence of ESBLs carrying gram-negative rods and consider how to treat
      their infections.

PMID- 11305002
TI  - [Clinical evaluation of metallo-beta-lactamase producing bacterium].
AB  - The metallo-beta-lactamase producing bacterium are increasing in recent years. We
      characterized cases infected or colonized with blaIMP, which is metallo-beta
      lactamase IMP-1 gene, positive gram-negative rods(GNRs). About half of the cases
      had malignant diseases as underliningg disease. When blaIMP positive GNRs were
      isolated, most of cases shows clinical signs of infection such as fever and
      elevation of C-reactive protein in serum. Most of strains were isolated from
      urinary samples and all patients from whom blaIMP positive bacterium were
      isolated from urinary samples were inserted urinary tract catheter. It was
      suggested that the insertion of catheters related to infection of blaIMP positive
      GNRs. No antibiotics were administered to several patients before the isolation
      of blaIMP positive GNRs although broad spectrum antibiotics such as carbapenems
      were administered to more than half of the patients. It is very important to
      prevent their dissemination in hospitals because most of blaIMP positive GNRs
      were isolated in same departments and showed identical pattern by pulsed field
      gel electrophoresis. And it is also important for treatment of the infectious
      disease due to blaIMP positive GNR to remove the catheter and improve general
      conditions of patients.

PMID- 11305003
TI  - [Glycopeptides].
AB  - Glycopeptides(Vancomycin(VCM), Teicoplanin(TEIC)) are effective against Gram
      positive cocci(GPC) and mainly prescribing for Methicillin Resistant
      Staphylococcus aureus(MRSA) infection in Japan. Mode of actions are little bit
      difference between VCM and TEIC, for example the rate of protein binding, post
      antibiotic effect and half-life time. Effect of glycopeptide depend on the above
      MIC. To keep the effective serum concentrations of the drug, recommended the
      method of loading dose for TEIC and the method of continuous drip infusions for
      VCM. Also keep the effective serum concentrations shows to shorten the duration
      of treatment and to protect for development of resistant strains. Biofilm
      diseases caused by P. aeruginosa, MRSA and MRSE are treated by combination
      therapy with Fosfomycin(FOM). The most powerful intensive chemotherapy (FOM +
      Sulbactam/Cefoperazon + Glycopeptides) shows superior effects against multiple
      infections caused by P. aeruginosa and MRSA.

PMID- 11305004
TI  - [Fundamental and clinical studies on beta-lactamase inhibitors].
AB  - Cluvulanic acid and sulbactam have been widely used in Japan as beta-lactamase
      inhibitors, and we will soon have tazobactam, the third beta-lactamase inhibitor.
      It will be available in combination with piperacillin(1:4), and expected
      excellent clinical efficacy in various infection, caused by class A, class D and
      class C beta-lactamase producing bacteria, including ESBLs producing gram
      negatives. The clinical usefulness of tazobactam/piperacillin might be exceeded
      those of drugs which combined with cluvulanic acid and sulbactam. However, it
      dose not inhibit class B beta-lactamase and large amount of class C beta
      lactamase. There are some reports of newer beta-lactamase inhibitors, which show
      much more strong activities against class C or even against class B beta
      lactamase in fundamental studies. Continuous studies will be needed to these
      agent for the future clinical use.

PMID- 11305005
TI  - [Combination chemotherapy].
AB  - Although most cases of infections in humans with normal host defenses can be
      treated with a single antimicrobial agent today, there are several cases to whom
      combination chemotherapy should be adopted. Five reasons have been advanced to
      justify the use of antimicrobial combinations: prevention of the emergence of
      resistant organisms, control of polymicrobial infections, initial therapy when
      causative organism is unclear, appearance of synergism, and management of
      infections in immunocompromised host. But, a clear advantage has been difficult
      to demonstrate in vivo. Furthermore, inappropriate use of antimicrobial
      combinations may lead patients to antagonism, cost, and even adverse effects.
      Therefore, antimicrobial combination therapy requires careful evaluation prior to
      clinical use.

PMID- 11305006
TI  - [Combination therapy of antibiotics and intravenous immunoglobulin].
AB  - A large scale multicenter randomized controlled study was conducted to evaluate
      the efficacy of intravenous immunoglobulin in combination with IPM/CS and AMK in
      504 evaluable patients who did not respond by 3 day therapy with beta-lactum and
      aminoglucoside. Immunoglobulin 5 g was administered 3 days to the patients
      allocated to immunoglobulin group. A completely automatic computer evaluation was
      performed according to the criteria determined by the committee. The response
      rate was 61.5% in immunoglobulin group and 47.3% in control group(p < 0.001).
      Intravenous immunoglobulin is considered effective for severe infection when used
      as combination therapy with antibiotics.

PMID- 11305007
TI  - [Antibiotics--TAZ/PIPC, synercid, linezolid, everninomicin].
AB  - The increasing resistance among Gram-positive cocci have been accompanied by
      their increasing frequency as cause of severe infection. Thus new antimicrobial
      agents, TAZ/PIPC, synercid and linezolid, are in various stages of development.
      TAZ/PIPC, a combination drug of a new beta-lactamase inhibitor tazobactam and
      piperacillin at ratio in 1 to 4 has a broad spectrum of antimicrobial activity.
      Evidence from randomized clinical trials in adults in Japan has shown that
      TAZ/PIPC is superior to PIPC as a drug for complicated urinary tract infection.
      Synercid is a streptogramin antibiotic. The spectrum of activity of synercid is
      similar to vancomycin. Furthermore, most of E. faecium were susceptible. The
      efficacy of synercid in clinical trials in patients infected with VREF was 65
      70%. Linezolid is a member of the oxazolidinones. The antimicrobial spectrum of
      linezolid is similar to that of vancomycin. In the US, patients with significant
      infection caused by resistant Gram-positive organisms(mostly VREF) were treated
      with linezolid. The efficacy of linezolid was about 75%. The clinical trials for
      everninomicin had been discontinued because of insufficient clinical data
      supporting its efficacy and safety.

PMID- 11305008
TI  - [Injectable quinolones].
AB  - Fluoroquinolones have been used worldwide against a variety of infections because
      of their potent antibacterial activity and good pharmacokinetics. In Europe and
      USA, ciprofloxacin and levofloxacin showed a good therapeutic efficacy for the
      past decade by sequential therapy for infections caused by Gram-negative bacteria
      including Pseudomonas aeruginosa and Gram-positive pathogens including penicillin
      resistant Streptococcus pneumoniae. Recently, injection form of ciprofloxacin was
      launched in Japan, and pazufloxacin, gatifloxacin, and sitafloxacin are under
      development. Appropriate usage of these injectable quinolones in Japanese medical
      practice should be established from the potency of each drug, the surveillance
      data of drug-resistance, and the experience in Europe and USA.

PMID- 11305009
TI  - [Prospect for the development of antibacterial agents with new mode of action].
AB  - Since there are no antibacterial agents to which there are no resistant bacteria,
      antibacterial agents with new mode of action are strongly demanded. Here, I
      describe the recent research for new targets and novel compounds that are active
      against the new targets. Proteins such as DnaA involved in DNA replication,
      deformylase and aminoacyl tRNA synthetase involved in protein synthesis, Mur
      peptide synthetases of peptidoglycan synthesis, FtsZ in cell division, two
      component signaling system, quarum sensing system and efflux pumps are targeted
      and several inhibitors against deformylase, two-component signaling system and
      efflux pumps are reported. Unknown essential genes in bacteria are also explored
      in order to find new targets.

PMID- 11305010
TI  - [Acute coronary syndromes].
AB  - Recently, unstable angina, acute myocardial infarction and sudden cardiac death
      have often been put together under the name 'acute coronary syndromes', because
      almost all of these conditions have been shown to be caused by thrombotic
      occlusion of a coronary artery following atherosclerotic plaque disruption. Acute
      coronary syndromes occur more frequently in the coronary arteries with no
      significant organic stenosis than in those with a higher degree of stenosis. A
      plaque prone to disruption has a thin fibrous cap, a large lipid core and
      increased infiltration of macrophages and T lymphocytes. The elimination or
      control of risk factors for atherosclerosis such as dyslipidemia, hypertension,
      smoking, diabetes mellitus, obesity and lack of exercise is essential for the
      prevention of acute coronary syndromes.

PMID- 11305011
TI  - [Clinical and fundamental studies of streptococcal toxic shock syndrome].
AB  - Streptococcal toxic shock syndrome(STSS) is known to progress rapidly into septic
      shock and multiple organ failure with frequently necrotizing fasciitis, and high
      mortality (approximately 40%). The diagnosis of STSS is confirmed based on the
      diagnosis criteria induced by the working group of the United State. Several
      extracellular products such as SPE A, B, and C having pyrogenic and
      superantigenic activity as well as SPE F, SPE G, H, J, SME Z, SME Z2, SSA are
      likely to involved in the pathogenesis of STSS. Recent studies have demonstrated
      an important role of certain cytokines, such as TNF-alpha, in laboratory animals.
      The exact role of such products in the pathogenesis of STSS, however, is
      currently unknown. The role of several virulence factors of group A streptococci
      in the pathogenesis of STSS was discussed in this review.

PMID- 11305012
TI  - [Vascular development and regenerative medicine].

PMID- 11305013
TI  - [Diagnosis and treatment of kidney diseases in the elderly].

PMID- 11305014
TI  - [Matrix metalloproteinase and vascular remodeling].

PMID- 11305015
TI  - [Causative genes in Alzheimer's disease].
AB  - Recently, some Alzheimer-associated genes have been found: amyloid precursor
      protein (APP), apolipoprotein E (apoE), presenilin 1 (PS-1) and presenilin 2 (PS
      2). First, we examined mutations of APP, PS-1, and PS-2 genes in familiar
      Alzheimer's disease (FAD) (7 cases) found in San-in district by single-strand
      conformation polymorphism and sequence analysis. These seven cases with FAD did
      not show any mutations of APP, PS-1, and PS-2 genes. Other susceptibility genes
      of FAD still remain to be not identified. Many reports have established that apoE
      genotype distribution for the epsilon 4 allele is a susceptibility factor for the
      earlier onset and more rapid progression of Alzheier's disease (AD). However, the
      cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors
      may be associated with development of SAD. Second, we investigated the
      association between polymorphisms of the estrogen receptor (ER) alpha gene and
      SAD. The frequencies of P and X alleles in SAD were significantly higher than
      those in the control group (p < 0.05). Polymorphisms of the ER alpha gene may be
      a genetic risk factor for SAD. The apoE genotype is a genetic factor closely
      related SAD, but it is not full by appreciated how apoE has an effect on
      developing AD. There are few reports on the quantitative change of apoE, namely
      the expression of apoE mRNA. Third, ApoE mRNA level in the brains of patients
      with Alzheimer's disease (27 cases) and Down's syndrome (11 cases) was determined
      by reverse transcriptase-polymerase chain reaction (RT-PCR). ApoE mRNA level in
      the DS as well as AD was significantly higher than that in control group (p <
      0.05, p < 0.05, respectively). High levels of apoE mRNA in AD and DS may play an
      important role in the development of Alzheimer pathology.

PMID- 11305016
TI  - [Suggestions from a centenarian study--aging and inflammation].
AB  - With the numbers of elderly increasing rapidly, it is important for both
      individuals and society that the oldest old maintains autonomy. To know how to
      attain successful aging, we investigate the status of centenarians. The
      characteristics of centenarians in Tokyo is 1) low level of nutritional
      parameters, 2) low level of cholesterol and HDL-cholesterol, 3) low level of red
      blood cells and hemoglobin, 4) high level of CRP, 5) high level of homocysteine,
      6) high level of von Willbrand factor. The incidence of dementia is 59.3%. Are
      these characteristics due to aging itself or other factors? We examined the
      effect of nutritional status, inflammation and level of homocysteine on the
      characteristics. The level of albumin is associated with serum level of lipid,
      RBC, ADL and cognitive function. The level of CRP is related to the level of
      albumin, suggesting that inflammation is related to nutritional status. The level
      of homocysteine is associated with the level of von Willbrand factor, suggesting
      that homocysteine is related to endothelial injury. From these data, we propose
      the hypothesis that proinflammatory status is associated with aging, resulting in
      a part of characteristics of centenarians. Homocysteine is partly responsible for
      endothelial injury. Intervention to suppress proinflammatory status and
      homocysteine level may promote QOL in the oldest old.

PMID- 11305017
TI  - [Gene and elderly hypertension].

PMID- 11305018
TI  - [Long-term care insurance].

PMID- 11305019
TI  - [The function as doctor].

PMID- 11305020
TI  - [The function as visiting nurse].

PMID- 11305021
TI  - [Proposals for standardization of the procedure of home help services and for
      promoting use of services for those who are not eligible for care insurance
      services].

PMID- 11305022
TI  - [Knowledge and utilization of comprehensive geriatric assessment in Japan].

PMID- 11305023
TI  - [Practical use of informal services and cooperation with psychologists under the
      long-term care insurance].
AB  - Home care of patients is mainly performed by visiting nurses. To adequately
      perform the care, many type of knowledge are needed. Especially psychological
      approaches can minimize the pain to the patients and their family and shortening
      its duration and raising the efficacy of the treatment. Cooperation with clinical
      psychologists can be effective. We present three cases who were difficult to help
      by nurses alone Thus, Nurses provided in cooperation with the psychologists.
      First case was a 27-year-old man with cerebral palsy. Second case was a 55-year
      old man with lung cancer, terminal stage. Third case was a 60-year-old man with
      amyotrophic lateral sclepsis. Through these different cases, we recognized the
      difficulties of medical care at home and also the importance of cooperation with
      psychologist. With the aging of society, the amount and type of home care needed
      will increase. Under long term insurance, the various type of knowledge,
      especially, psychological approaches is important. At the same time, training and
      education in this field for visiting nurses is required.

PMID- 11305024
TI  - [Correlative network among nurses, PTs and OTs in rehabilitation care at home].

PMID- 11305025
TI  - [A continuous education system for Japanese home care nurses].

PMID- 11305026
TI  - [Role of visiting nurse in long-term care insurance].

PMID- 11305027
TI  - [Cultural climate and social custom for longevity region, Okinawa].

PMID- 11305028
TI  - [Longevity related genes].

PMID- 11305029
TI  - [Pathomorphological findings of healthy centenarians].

PMID- 11305030
TI  - [Physiological requirements for longevity].
AB  - Genetic background is an important factor for longevity. Life-style and
      environmental factors, such as nutrition, physical activity, smoking and alcohol,
      are also important. For example, obesity is negatively associated with health and
      longevity. It is known that dietary restriction is the most consistent method of
      extending life span in rats. In human, however, under nutrition as well as over
      nutrition is a risk factor for a short life. Losing weight is often dangerous in
      the elderly, in whom reserved physiological functions are limited. Smoking,
      diabetes mellitus and hypertension accelerate human aging, while physical
      activity and a moderate amount of alcohol is good to live long. Preventive
      medicine and health support are also important to promote longevity. Good results
      of new strategies such as custom-made health support and preventive treatment are
      anticipated in the near future. Accumulation of basic data in human aging and
      health are essential to the practice of preventive medicine and health support. A
      new comprehensive longitudinal study was started at the National Institute of
      Longevity Sciences (NILS) in 1997 (NILS-Longitudinal Study of Aging, NILS-LSA).
      The results of this study should be helpful for the practice of preventive
      medicine and health support.

PMID- 11305031
TI  - [Nitric oxide-dependent inhibition of platelet aggregation in elderly patients
      with hypercholesterolemia].
AB  - Hypercholesterolemia reduces production of nitric oxide (NO), a potent inhibitor
      of platelet aggregation, in endothelial cells. Recently platelet has been found
      to have NO synthase. Hypercholesterolemia may influence platelet NO production.
      We investigated NO-dependent inhibition of platelet aggregation in elderly
      hypercholesterolemic patients with total cholesterol (Tchol) of 240 mg/dl or more
      (n = 21). In elderly controls with Tchol less than 240 mg/dl (n = 61), L-arginine
      (5-50 mM) inhibited ADP-induced platelet aggregation in a dose-dependent manner
      (42.4% inhibition at 50 mM). However, L-arginine did not inhibit platelet
      aggregation in elderly hypercholesterolemic patients. L-arginine increased cyclic
      GMP production in elderly controls, but not in hypercholesterolemic patients (p <
      0.02). Hypercholesterolemic patients showed increased platelet aggregation
      compared with elderly controls(p = 0.018). L-nitro-arginine methyl ester 12.5-50
      uM increased platelet aggregation in both groups. Superoxide dismutase improved L
      arginine inhibition of platelet aggregation in elderly hypercholesterolemic
      patients (p = 0.02). LDL cholesterol of 160 mg/dl or more was an independent
      predictor for loss of L-arginine inhibition of platelet aggregation (relative
      risk 3.9, p = 0.0098). This result suggests that hypercholesterolemia causes
      decreased NO-dependent inhibition of platelet aggregation due to reduced NO
      utilization. NO-dependent platelet aggregation may be a powerful tool for
      detection of vascular injury.

PMID- 11305032
TI  - [Assessment by means of a Minimum Data Set of the changes of mental and physical
      status of elderly patients with dementia during two years of
      institutionalization].
AB  - Using a Minimum Data Set, we studied how the mental and physical conditions of
      elderly people with dementia changed during two years of institutionalization.
      Fifty-five patients with dementia of Alzheimer's type (DAT) and 25 with vascular
      dementia (VD) admitted to the dementia ward in Kyoto Higashiyama Geriatric
      Hospital were investigated. We assessed them at the time of their
      institutionalization, and every three months for two years. On
      institutionalization, a difference between DAT and VD was noted in the group in
      which more than 10 areas of Resident Assessment Protocols (RAPs) were triggered.
      The areas of delirium, communication, behavioral problem, activities, activities
      of daily living, dehydration/fluid maintenance, and psychotropic drugs were
      evenly triggered in both dementia groups. In the DAT group, however, mood state
      and dental care were also highly triggered while urinary incontinence, falls and
      nutritional status were highly triggered in the VD group. Three months later,
      marked improvements were observed in all of the above areas. However, RAPs areas
      gradually increased subsequently, and there was marked difference in the areas
      and their course of progression between the dementia groups. In the DAT group,
      the trigger rate of the areas of communication, activities of daily living,
      urinary incontinence, dental care, nutritional status and falls gradually
      increased after 6 months of evaluation. However, the trigger rate in only three
      areas, such as communication, visual function and urinary incontinence, become
      higher, but their patterns of increase were irregular. Mental and physical
      conditions of the patients with dementia were different in each dementia subtype
      on institutionalization, but these conditions improved soon after. However, the
      conditions were gradually became worse, and the pattern was different in each
      dementia group: DAT showed a slow and steady decline, but VD showed irregular
      progression and differed among individuals.

PMID- 11305033
TI  - [Memory function in patients with Parkinson's disease: in relation to
      neuropsychological tests and cerebral blood flow].
AB  - We conducted a neuropsychological comparison between Parkinson's disease (PD; n =
      24) and healthy control subjects (n = 12) using Rey's auditory-verbal learning
      test (RAVLT) and the Rey-Osterrieth complex figure test (RCFT) assessing memory
      function. In addition, to determine the function of cortical and subcortical
      areas, we measured the regional cerebral blood flow (rCBF) using N-isopropyl
      p[123I]-iodoamhetamine (123I-IMP) and single photon emission computed tomography
      (SPECT) and analyzed the relationships between brain regions and memory function.
      On the RAVLT, significant group differences in recall words were found on all
      learning trials between patients with PD and control subjects, whereas
      recognition, learning rate and forgetting rate were basically the same. In
      addition, the primacy/recency effect was statistically equal for both groups.
      Results suggest faulty retrieval mechanisms in PD, whereas encoding and retention
      procesess did not prove to be affected. There were significant correlations
      between perfusion of the prefrontal and parietal cortices and total number of
      free recall in five trials. On the RCFT, recalls after 30 sec and 30 min were
      impaired in patients with PD although no significant difference in accuracy
      scores obtained in copy was noted. A percent recall score calculated using the
      formula 100 x [1 - (copy-recall)/copy] was also decreased in patients with PD.
      There were significant correlations between perfusion of the occipital and
      parietal cortices and percent recall score. Our data suggest that auditory memory
      deficits based on the RAVLT in PD may be mainly related to frontal and parietal
      cortical dysfunction, while visual recall deficits based on the RCFT may be
      related to the parieto-occipital cortical dysfunction.

PMID- 11305034
TI  - [Music therapy induced alternations in natural killer cell count and function].
AB  - The effects of music therapy on natural killer (NK) cell count and activity
      (NKCA) were studied in 19 persons. Alzheimer's disease, cerebrovessel disease and
      Parkinson's disease subjects were assigned to a music therapy. Blood samples were
      drawn at rest and after completion of music therapy. Music therapy did not change
      the number of circulating lymphocytes. The percentage of NK cells increased
      during music therapy, along with an increase in the NK cell activity. The
      proportion of T cells, CD4 and CD8 did not change significantly during music
      therapy. One hour after the music therapy session, plasma adrenaline increased
      but cortisol and noradrenalin did not change. The results indicate that music
      therapy can significantly increase NK cell count and activity. The change in NK
      cell and function were independent of neuro-degenerative diseases.

PMID- 11305035
TI  - [Influence of acupuncture and moxibustion on QOL of the elderly living in nursing
      home and care house].
AB  - To clarify the influence of acupuncture therapy on the quality of life (QOL) of
      the elderly, the acupuncture and moxibustion were performed on 35 elderly
      subjects (8 men and 27 women) with a mean age 79.1 living in nursing homes and
      elderly care houses. The acu-points were chosen according to their symptoms.
      Changes in pain and other complaints, body condition, appetite, sleep, bowel
      movement and activity of daily living (ADL) were evaluated by questionnaires. A
      total of 38 symptoms were reported. A high rate of improvement was seen in pain
      and stiffness. For example, there was 86% improvement in low back pain, 84% in
      knee joint pain and 82% in shoulder stiffness. Concerning body conditions,
      decrease of fatigue, relaxed of feeling, improvement in appetite, sleep and bowel
      movement were observed. Furthermore, gait and ADL were also improved. These
      results suggested that acupuncture and moxibustion are useful to improve QOL in
      the elderly.

PMID- 11305036
TI  - [A survey on how medical student consider end-if-life care in the elderly].
AB  - We examined the way medical students think about end-of-life care in the elderly
      by a questionnaire survey. The major variables of the evaluation instrument
      included the students' idea of the special nature of end-of-life care for the
      elderly, the necessity for disclosure of the name of disease, consideration for
      patient's age on disclosure, advance directives concerning their life-sustaining
      treatment, and communication concerning preferences for end-of-life care. The
      final items on the instrument asked for student comments about end-of-life care
      in the elderly. We analyzed this qualitative data using the process of
      immersion/crystallization. We received 95 responses, and of these 65 (68%)
      provided written commentaries that were analyzed using qualitative techniques.
      Fifty-nine (62%) students pointed out the special nature of end-of-life care in
      the elderly and most of them (96%) needed the disclosure of the name of disease.
      Fifty-two (55%) students agreed with advance directives for end-of-life care and
      88 (93%) students pointed out the importance of communication with regard to
      patients' preferences. Medical students' concerns about end-of-life care in the
      elderly related to three major domains: 1) patient-physician relationship; 2) the
      procedures of end-of-life care; and 3) emotional and intuitive comments. These
      results suggest that in the education of geriatric medicine the patient
      physician's relationship about end-of-life care is important and we may need to
      introduce systematic lectures and practical training.

PMID- 11305037
TI  - [Three elderly cases of hyperostosis cranii with various clinical symptoms].
AB  - We report three elderly patients with hyperostosis cranii (HC). Patient 1 had two
      episodes of unconsciousness; patient 2, headache; and patient 3, dementia. On the
      basis of the classification of Moore using skull films, patients 1 and 2 showed
      hyperostosis frontoparietalis and patient 3 had hyperostosis frontalis interna.
      Electroencephalography showed transient generalized spike and slow wave complexes
      over the frontal lobes in patient 1. Magnetic resonance (MR) images showed
      frontal lobes compressed by the thickness of the frontal bones in all patients
      and thickened parietal bones in patients 1 and 2. Because findings in our series
      and in the literature suggest that HC may show unexpected neuropsychiatric
      symptoms, HC should be checked in elderly patients whose presenting symptoms
      include epilepsy, dementia, psychiatric disease, headache and so on. MR images
      should reveal the relationship between clinical symptoms and the deformation of
      brains by the skull.

PMID- 11305038
TI  - [Successful treatment of an elderly patient with idiopathic thrombocytopenic
      purpura accompanied with chronic subdural hematoma, using a Chinese herbal
      medicine, EK-49, and ascorbic acid].
AB  - An 88 year-old woman was admitted complaining of headache. CT scan of the head
      revealed a right subdural hematoma. She had been followed by a local physician
      because of chronic thrombocytopenia. Her peripheral platelet count on admission
      was 0.5 x 10(4)/microliter, with a high serum level of PAIgG. Bone marrow
      examination revealed marked increase of megakaryocyte. Idiopathic
      thrombocytopenic purpura(ITP) accompanied with chronic subdural hematoma was
      diagnosed. Transient increase of platelet count and improvement of subdural
      hematoma was obtained by administration of prednisolone. However, platelet count
      decreased with tapering of prednisolone. Then combined administration of a
      Chinese herbal medicine, EK-49, and ascorbic acid was started. Platelet count
      gradually increased and no adverse effects were experienced. These results
      indicated that elderly patients with chronic subdural hematoma can be treated non
      invasively, and that a combination of EK-49 and ascorbic acid may be effective in
      the treatment of refractory ITP.

PMID- 11305039
TI  - [Two elderly patients with sarcoidosis and Sjogren's syndrome].
AB  - Two elderly patients with sarcoidosis complicated with Sjogren's syndrome are
      described. Case 1: A 70-year-old woman was admitted due to dry eyes. Histological
      examination of a minor salivary gland specimen revealed lymphocytic infiltration,
      which was compatible with Sjogren's syndrome. Because uveitis was demonstrated,
      transbronchial lung biopsy (TBLB) was performed, to confirm a diagnosis of lung
      sarcoidosis. Histological examination of TBLB showed non-caseating granulomas
      compatible with sarcoidosis. Case 2: A 70-year-old woman was admitted due to
      dyspnea on exercise and blurred vision. Two years previously, Sjogren's syndrome
      was diagnosed because of a positive Shirmer test and positive SS-A antibody.
      Result of ophthalmic examination were compatible with uveitis. Histological
      examination of TBLB showed non-caseating granulomas compatible with sarcoidosis.
      Certain similarities between sarcoidosis and Sjogren's syndrome in terms of
      immunological aspects have attracted attention. In the present manuscript, a
      possible relationship between the two diseases as well as the characteristics of
      elderly sarcoidosis are discussed.

PMID- 11305040
TI  - [A case of recurrent ischemic attacks: consecutive diffusion-weighted magnetic
      resonance imaging].
AB  - A 61-year-old man with recurrent ischemic attacks was examined by diffusion
      weighted MRI (DWI). He had reversible right hemiparesis and dysarthria five times
      during admission. DWI was obtained on the first two attacks, the last attack and
      four days after the last attack. The first two attacks were clinically diagnosed
      as transient ischemic attack (TIA), and the last attack was cerebral infarction
      with symptoms persistent for one week with Babinski's sign. In the first and last
      images the apparent diffusion coefficient (ADC) declined to approximately 80% of
      the corresponding area. We conclude that different images showed TIA with ADC
      declining, TIA without ADC declining, the hyperacute phase of cerebral infarction
      before ADC declining, and cerebral infarction after ADC declining. Consecutive
      DWIs were helpful to understand the character of recurrent ischemic attacks.

PMID- 11305041
TI  - [Review of the Koganei Study].

PMID- 11305042
TI  - [Assessment of anti-tremorogenic drugs using nicotine-induced tail-tremor model
      and elucidation of the mechanism].
AB  - Repeated administration of nicotine causes a tremor only in the tail (tail
      tremor) of rats. The tremor is accompanied with locomotor hyperactivity without
      rigidity and immobility of the whole body, suggesting the involvement of the
      mechanism associated with the movement. The tail-tremor induced by nicotine was
      suppressed by nicotinic acethylcholine (nACh) receptor antagonists, but not by
      muscarinic acethylcholine (mACh) receptor antagonists. Moreover, the tail-tremor
      was suppressed by beta-adrenoceptor antagonists and benzodizepines. The tremor at
      rest is observed only in Parkinson's disease, which is improved by the use of
      mACh receptor antagonists. An essential tremor is one of the typical tremor
      connected with the movement (postural tremor) and improved with beta-adrenoceptor
      antagonists. These findings and results suggest that the nicotine-induced tail
      tremor is useful for the study of the essential tremor as an animal model. On the
      other hand, daily administration of nicotine resulted in an augmentation of the
      tail-tremor. The development of the tail-tremor was suppressed by nACh receptor
      antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide
      (NO) synthase inhibitors. These results suggest that central nACh receptors are
      essential for the onset and further development of the tail-tremor induced by
      repeated administration of nicotine, and that NO formation mediated by NMDA
      receptors is involved in the developmental mechanisms.

PMID- 11305043
TI  - Superoxide scavenging activities of sixty Chinese medicines determined by an ESR
      spin-trapping method using electrogenerated superoxide.
AB  - Superoxide-scavenging activities of 60 kinds of Chinese herbal medicines were
      determined accurately by an electron spin resonance (ESR) spin-trapping technique
      using 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) as a spin-trapping reagent. As a
      source of superoxide in this method, superoxide generated by one-electron
      reduction of the oxygen molecule in dimethyl sulfoxide solution was used. As a
      result of these studies, very powerful scavenging activity was found in Chinese
      medicines for inflammation, diseases of blood circulation and for tumors.

PMID- 11305044
TI  - [Cytotoxic activity and cytokine gene induction of Asp-hemolysin to vascular
      endothelial cells].
AB  - We examined the effects of Asp-hemolysin from Aspergillus fumigatus Fresenius
      Muramatsu strain on the viability and cytokine gene expression of human umbilical
      vein endothelial cells (HUVEC). The cell viability of HUVEC was reduced to 50% by
      100 micrograms/ml of Asp-hemolysin. However, lower concentration of Asp-hemolysin
      (< 30 micrograms/ml) had no effect on the cell viability. The mRNA expression of
      such cytokines as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1
      beta, IL-6, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF)
      were also observed in HUVEC cultured with 30 micrograms/ml of Asp-hemolysin.

PMID- 11305045
TI  - [Effects of low density lipoprotein and oxidized low density lipoprotein on the
      cytotoxic activity of Asp-hemolysin to murine macrophages].
AB  - We examined the effects of human low density lipoprotein (LDL) and oxidized LDL
      (Ox-LDL) on the cytotoxic activity of Asp-hemolysin from Aspergillus fumigatus
      Fresenius-Muramatsu strain to mouse peritoneal macrophages (M phi). The
      inhibitory effects of LDL and Ox-LDL on the cytotoxic activity of Asp-hemolysin
      to M phi increased in a dose-dependent manner, and the effect of Ox-LDL was
      greater than the inhibitory effect of LDL. Furthermore, the binding of Asp
      hemolysin to LDL or Ox-LDL was observed by western blot analysis of the culture
      medium. These results suggest that the inhibition by LDL or Ox-LDL on the
      cytotoxic activity of Asp-hemolysin to M phi was due to the binding of LDL or Ox
      LDL to Asp-hemolysin in the culture medium.

PMID- 11305046
TI  - [Evaluation of absorbed dose-distribution in the X-ray or gamma-irradiator for
      blood products].
AB  - Irradiation of blood products abrogates the proliferation of lymphocytes present
      in cellular component, which is currently the only accepted methodology to
      prevent transfusion-associated graft versus host disease (TA-GVHD). A range of
      irradiation dose levels between 15 Gy and 50 Gy is being used, but the majority
      of facilities are employing 15 Gy. It should, however, be recognized that the
      delivered dose in the instrument canister might differ from the actual dose
      absorbed by the blood bag. This study have evaluated the actual dose distribution
      under practical conditions where a container was loaded with blood products or
      water bags, or filled with distilled water. This approach provides data that the
      maximum attenuation occurred when the container was completely filled with a
      blood-compatible material. Thus, an error of approximately 20 percent should be
      considered in the dose measured in the in-air condition. A dose calibration in an
      in-air condition may lead to substantial underexposure of the blood products. A
      dose distribution study using adequately prearranged exposure period verified
      that the absorbed dose of 15 Gy was attained at any point in the container for
      both linear accelerator and gamma-irradiator. The maximal difference in the
      absorbed dose between measured points was 1.5- and 1.6-fold for linear
      accelerator and gamma-irradiator, respectively. In conclusion, using blood
      compatible materials, a careful dose calibration study should be employed in
      which the absorbed dose of 15 Gy is obtained at the point where the lowest dose
      could be expected.

PMID- 11305047
TI  - [Estimation of radiation exposed area by the nuclear accident occurred at Tokai
      village using ESR measurements of household sugar].
AB  - The area of radiation exposure by the nuclear accident occurred at Tokai village
      in 1999 was estimated by the ESR measurement of 95 household sugar samples
      collected from the accident area. These samples were roughly classified into
      three types of sugar, fine white sugar, fine brown sugar and coarse brown sugar.
      The control fine white sugar showed no radical in the ESR spectrum, while those
      of fine brown sugar and coarse brown sugar showed the presence of a small amount
      of radicals. It was also shown that, among these three kinds of sugar, the
      radical concentration of fine white sugar sampled from wooden houses at the area
      similar to each other did not vary much with the samples, while those of fine
      brown sugar and coarse brown sugar varied to a considerable extent. Thus, the
      fine white sugar is considered to be more suitable for the estimation of the
      level of radiation exposure. The radical concentration of each fine white sugar
      sample was plotted against the distance from the site of the nuclear accident
      with a correction of the difference in the shielding effect between concrete
      houses and wooden houses. The samples obtained at more than 2 km north of the
      site of nuclear accident showed no ESR spectral signal to a detectable extent. On
      the other hand, the ESR spectra were observed from the samples obtained within 10
      km south and 4 km west of the accident site. These results suggest that the
      radiation exposure by the contaminant blown by the northeast wind blowing on the
      day of the accident may occur at the south and west areas.

PMID- 11305048
TI  - [Pathogenesis mechanism in ear fullness in otosclerosis].
AB  - To clarify the mechanism underlying ear fullness in otosclerosis, we studied the
      relationship between clinical features and examinations. Subjects were 116
      otosclerosis patients (140 ears). The presence or absence of ear fullness was
      judged from a questionnaire in initial diagnosis or a chart description. Ear
      fullness was observed in 44 ears (31%) and absent in 96. The averaged air and
      bone conduction hearing levels (500 Hz-4 k Hz) in initial diagnosis were
      significantly lower in the group with ear fullness. The difference in averaged
      hearing was mainly apparent at 2 k Hz and 4 k Hz. The difference in hearing at
      lower frequencies (125 Hz, 250 Hz, and 500 Hz) and higher frequencies (2 k Hz, 4
      k Hz, and 8 k Hz) was significantly larger in the group of ear fullness. From
      these results, we postulated that ear fullness in otosclerosis is caused by
      fixation of the stapes. The psychoacoustic abnormal sensation caused by lower
      input of lower-frequency sound or incomplete fixation of the stapes may cause ear
      fullness. Further study is needed to clarify the pathogenesis of ear fullness in
      different ear pathologies.

PMID- 11305049
TI  - [Evaluation of hearing recovery and a grading system established by the Research
      Group on Sudden Deafness of the Japanese Ministry of Health and Welfare].
AB  - A grading system for sudden deafness has been established by the Research Group
      on Sudden Deafness of the Japanese Ministry of Health and Welfare. According to
      this grading system, sudden deafness cases are classified according to the
      initial hearing level and the vestibular symptoms. Few clinical analyses of
      sudden deafness cases have been made using this grading system. In this study,
      263 sudden deafness cases were classified into 6 groups based on the grading
      system. All of the cases presented with an initial hearing level of more than 40
      dB and underwent treatment within 1 week of the onset of symptoms. The
      relationship between the grading system and hearing recovery is discussed. Fixed
      hearing levels with a good prognosis were grades 2b, 2a, 3b, 3a, 4b and 4a. To
      quantitatively evaluate hearing recovery, the average hearing recovery rate and
      the percentage of the complete recovery cases were analyzed for each group.
      Average hearing recovery was ranked into five levels, regardless of the
      evaluation method. Grades 2b and 3b were the best, and grade 4a was the worst.
      After grades 2b and 3b, grade 2a was the second best, grade 3a was the third, and
      grade 4b was the fourth. The cases included in grades 2 and 3 were more strongly
      effected by whether the cases had vestibular symptoms or not than by their
      initial hearing levels. When grade 4 cases were classified by their initial
      hearing level, a large difference existed among grade 4a cases with regard to
      whether they presented with an initial hearing level of under or more than 100
      dB. The hearing recovery of grade 4a cases with an initial hearing level of less
      than 100 dB was almost the same as that of grade 3a. However, the hearing
      recovery of grade 4b cases varied only slightly. Consequently, some ranges of
      initial hearing level exhibited similar degrees of hearing recovery. In cases
      without vestibular symptoms, the range of initial hearing levels was 40-89 dB.
      These cases had a 60% chance of complete recovery, and the hearing recovery rate
      was 80% on average. In cases with vestibular symptoms, the range of initial
      hearing levels was 60-99 dB. These cases had a 40% possibility of complete
      recovery, with an average hearing recovery rate of 60%. After comparing the
      initial grades and the final grades using the same grading system, the majority
      of grade 2 and 3 cases attained a grade 1 fixed hearing level. However, most
      grade 4 cases had a grade 3 fixed hearing level.

PMID- 11305051
TI  - [Case report of a malignant schwannoma in the neck with rare pathological
      findings].
AB  - In this report, we describe a rare case of a malignant transformation in an
      ancient schwannoma arising in the right side of the neck of a 51-year-old man.
      The patient was referred to our hospital because of a mass that had been present
      for three years. The mass, measuring about 4 x 2 cm, was elastic and hard,
      relatively well demarcated, and movable upon palpation. Aspiration cytology was
      performed, but the diagnosis was unclear histologically. The patient was placed
      under general anesthesia and the tumor was totally excised. The tumor, which was
      easily excised, was connected to the sympathetic nerve at both poles. The
      histological diagnosis was a malignant transformation in an ancient schwannoma.
      The patient showed no clinical manifestations suggesting neurofibromatosis. Three
      months after the operation, a recurrent tumor, which was not resectable, was
      discovered extending deep into the skull base. The patient underwent two
      operations and two courses of radiation therapy, but the tumor metastasized to
      the lung and liver. He died of pulmonary failure eleven months after the initial
      treatment.

PMID- 11305050
TI  - [Costimulatory molecule expression on allergen-stimulated PBMC in cedar
      pollinosis subjects].
AB  - B7-1 (CD80) and B7-2 (CD86) play important roles in the differentiation of Th1
      and Th2 phenotypes. CD40-CD40L interaction supports the expression of CD80 and
      CD86 on antigen-presenting cells. Blocking studies suggest these molecules also
      play important roles in sensitization to a cedar pollen antigen by, but very few
      studies have concerned their effects on subsequent induction by antigens. We
      investigated the roles of CD80, CD86, and CD40 in the differentiation of Th1 and
      Th2 subsets after stimulation with the antigen in subjects with cedar pollinosis.
      Peripheral blood mononuclear cells (PBMC) were isolated from 12 subjects with
      pollinosis and 11 healthy controls and stimulated with cedar pollen extract.
      After in vitro stimulation, CD80, CD86, and CD40 expression on CD19+ cells were
      analyzed by flow cytometry. The production of type 1 and type 2 cytokines in
      culture supernatants was measured by FLISA. Proliferation studies were conducted
      in the presence or absence of anti-CD40 or CD86 mAbs. After in vitro stimulation,
      CD86 and CD40 were significantly up-regulated following stimulation in pollinosis
      subjects (p = 0.02 and p = 0.04). A significantly higher level of IL-5 (p = 0.02)
      was produced by PBMC of pollinosis subjects than by those of controls. Allergen
      induced proliferation and IL-5 production of PBMC of pollinosis subjects were
      inhibited by anti-CD86 mAb but not CD40 mAb. These results indicate that the Th2
      response predominated in pollinosis subjects and that CD86 rather than CD80 may
      be the costimulatory molecule involved in the allergen-induced activation of
      PBMC.

PMID- 11305052
TI  - [Fatal pulmonary embolism developing after tympanoplasty: a case report and
      incidence of pulmonary embolism at Toyooka Hospital].
AB  - We report a case of fatal pulmonary embolism (PE) developing after tympanoplasty.
      A 69-year-old woman underwent type III tympanoplasty for a middle ear
      cholesteatoma under general anesthesia. Operating time was 3 hours 27 minutes and
      anesthesia lasted 5 hours 9 minutes. The next morning, 14 hours 5 minutes after
      returning to the recovery room, the patient lost consciousness while getting out
      of bed. Although consciousness recovered transiently, she went into shock with
      cardiopulmonary arrest. Heart beat was regained after resuscitation with
      artificial respiration and cardiac massage, but her blood pressure was unstable.
      Echocardiography revealed right ventricular overload and pulmonary hypertension.
      Because PE was suspected, thrombolytic therapy was conducted to stabilize
      hemodynamics. Enhanced computed tomography (CT) of the chest showed bilateral
      pulmonary thromboembolism. The patient died of hypoxic encephalopathy 23 days
      after PE onset. We have seen 40 cases of PE at our hospital in the last 70
      months. Five patients developed PE after surgery with a postoperative occurrence
      rate of 0.03% (5/16, 277), and 3 of them died. Enhanced CT in 19 of 21 cases
      (90.5%) before or just after the start of therapy for PE was useful in
      establishing the diagnosis. Although PE is rare in the field of otolaryngology
      and head and neck surgery, it may develop rapidly after any type of surgery
      resulting in a fatal outcome. It is thus important to establish diagnosis early
      and prevent such serious complications.

PMID- 11305053
TI  - Partial left ventriculectomy. The First Japanese Registry Report 1999.
AB  - OBJECTIVE: Partial left ventriculectomy has been performed without standardized
      inclusion/exclusion criteria. A registry has been established to accumulate
      experience with this procedure to identify indications, risks and benefits.
      METHODS: In response to a mailed inquiry, 90 cases were voluntarily registered
      from 28 Japanese institutions. RESULTS: Males (n = 67, 74.4%) predominated, and
      29 (32.2%) patients were over 60 years old. The underlying cardiac pathologies
      included dilated cardiomyopathy (n = 75, 83.3%), valvular disease (n = 8, 8.9%),
      the dilated phase of hypertrophic cardiomyopathy (n = 4, 4.5%), and others (n =
      3, 3.3%). Gender, age, etiology, papillary muscle excision and absent transplant
      indication did not significantly affect survival. Poorer preoperative condition,
      reduced contraction and decompensation necessitating emergency operation were
      each associated with a significantly higher risk. Hospitals performing less than
      5 cases had poorer results than more experienced institutions (p = .0019), which
      showed a tendency towards improved survival in the second half of their
      experience (p = .096). Hospital mortality (n = 29, 32.6%) and late death (n = 10,
      11.2%) were mainly from ventricular failure with few sudden deaths over a period
      of 63.6 patient years follow-up. Late mortality was equally distributed in the
      first year and leveled off with significantly improved cardiac functional class
      in survivors. CONCLUSION: Partial left ventriculectomy was associated with better
      survival in less symptomatic patients with better contractile reserve undergoing
      an elective operation preserving the papillary muscles. Avoidance of identified
      risk factors may allow better patient selection and improved survival in the
      current environment where rescue transplantation is not readily available. Long
      term follow-up is warranted with more registry data.

PMID- 11305054
TI  - Changes in right ventricular performance in elderly patients who underwent
      lobectomy using video-assisted thoracic surgery for primary lung cancer.
AB  - OBJECTIVE: Even though lobectomy using video-assisted thoracic surgery for
      primary lung cancer has been reported to be beneficial in terms of the
      perioperative outcome, changes in the right ventricular performance have not yet
      been reported. The aim of this study was to determine whether lobectomy by video
      assisted thoracic surgery is also advantageous with respect to the right
      ventricular performance in elderly patients who are 70 years old or older.
      SUBJECTS AND METHODS: Thirteen patients (mean age: 76 years) who underwent
      lobectomy using video-assisted thoracic surgery (Video-assisted Thoracic Surgery
      Group), and 10 patients (mean age: 76 years) who underwent lobectomy using a
      standard thoracotomy as a historical control group (Standard Thoracotomy Group)
      were studied. The hemodynamics and right ventricular ejection fraction were
      evaluated preoperatively, and at 6, 12, 24, and at 48 hours postoperatively.
      RESULTS: Postoperative values were expressed as a percentage of the preoperative
      values. The systemic vascular resistance index decreased to a greater extent in
      the Video-assisted Thoracic Surgery Group than in the Standard Thoracotomy Group.
      The pulmonary arteriolar resistance index at 24 hours postoperation tended to be
      higher in the Standard Thoracotomy Group than in the Video-assisted Thoracic
      Surgery Group. The stroke index, cardiac index, and right ventricular ejection
      fraction at 24 hours postoperation were each significantly higher in the Video
      assisted Thoracic Surgery Group than in the Standard Thoracotomy Group.
      CONCLUSION: Lobectomy using video-assisted thoracic surgery for elderly patients
      offers not only beneficial effects in the right ventricular afterload but also
      acceleration in the expected compensatory hyperdynamics during the acute
      postoperative phase.

PMID- 11305055
TI  - Bilateral internal thoracic artery T grafting for coronary artery
      revascularization. Angiographic assessment and mid-term outcome.
AB  - OBJECTIVES: We studied the early outcome of bilateral internal thoracic artery T
      grafting. METHODS: Coronary artery bypass grafting was studied retrospectively
      using bilateral internal thoracic artery T grafting in 51 patients. The T graft
      was made by anastomosing the free right internal thoracic artery to the in-situ
      left internal thoracic artery. Average patient age was 63.5 +/- 9.9 years, and
      the average number of anastomoses per patient was 3.6 +/- 0.9. In 35 patients,
      the right gastroepiploic artery (21 anastomoses in 20 patients), radial artery (1
      anastomosis), free left internal thoracic artery (1 anastomosis) and saphenous
      vein graft (14 anastomoses in 13 patients) were used as additional bypass
      conduits. RESULTS: Hospital mortality was 0%. The morbidity of stroke was 1.9% (1
      patient) and deep sternal infection 0%. Patency of the in-situ left internal
      thoracic artery was 49/50 anastomoses (98%) and that of the free right internal
      thoracic artery 81/84 anastomoses (96.4%). Mid-term coronary angiography in 7
      patients demonstrated patent anastomosis of the T graft. Acute myocardial
      infarction unrelated to graft failure occurred in 2 patients during follow-up.
      Other patients were evaluated by exercise stress tests every year and none
      exhibited myocardial ischemia in the areas of T graft coronary revascularization.
      Three-year actuarial survival rate was 100% and freedom from cardiac events 96%.
      CONCLUSIONS: The bilateral internal thoracic artery T graft provides satisfactory
      early and mid-term outcomes in properly selected patients.

PMID- 11305056
TI  - Wallstent endovascular prosthesis for the treatment of superior vena cava
      syndrome.
AB  - OBJECTIVE: We assessed the clinical outcome of self-expanding Wallstent
      endovascular prosthesis in the treatment of superior vena cava syndrome due to
      malignant tumors. METHODS: Eleven patients with malignant superior vena cava
      syndrome were treated by percutaneous implantation of the self-expanding
      Wallstent endovascular prosthesis across the stricture site. Patency was defined
      by the absence of symptoms and signs of superior vena cava syndrome. RESULTS: Ten
      of the 11 experienced complete symptomatic relief within 3 days of stent
      implantation. The remaining 1 did not benefit, and required a second procedure,
      dying of heart failure 5 days after stent implantation. Ten patients remain
      symptomatically free of superior vena cava syndrome to date or until death in
      follow-up lasting 17 to 227 days. CONCLUSION: Implantation of the self-expanding
      Wallstent endovascular prosthesis for malignant superior vena cava syndrome
      provides rapid symptomatic relief and improves the patient's quality of life.

PMID- 11305057
TI  - Mitral insufficiency associated with primary antiphospholipid syndrome and
      chronic renal failure.
AB  - We report a case of 52-year-old woman with primary antiphospholipid syndrome who
      developed mitral insufficiency and chronic renal failure. Continuous ambulatory
      peritoneal dialysis was started preoperatively due to thrombocytopenia that was
      aggravated by hemodialysis. Mitral annuloplasty was performed since the mitral
      valve was not severely damaged. Her postoperative hemodynamics were stable, and
      anticoagulant therapy was controlled easily. She recovered from severe
      thrombocytopenia while on continuous ambulatory peritoneal dialysis. Valvular
      heart disease is a well known feature of primary antiphospholipid syndrome, and
      there have been several reports about valve replacement in patients who had
      antiphospholipid syndrome with or without systemic lupus erythematosus. However,
      valve repair has been reported in only a few such patients. We believe that valve
      repair is better than valve replacement in patients with antiphospholipid
      syndrome because of its hypercoagulable tendency. In addition, it seems that
      continuous ambulatory peritoneal dialysis is a suitable method for the
      perioperative management of patients with antiphospholipid syndrome who suffer
      from chronic renal failure as well as thrombocytopenia, and require cardiac
      surgery under cardiopulmonary bypass.

PMID- 11305058
TI  - Valvuloplasty for aortic valve regurgitation resulting from cusp prolapse.
AB  - Three adults, 2 with tricuspid aortic valve and 1 with bicuspid valve, underwent
      valvuloplasty for aortic valve regurgitation resulting from cusp prolapse.
      Surgical procedures consisted of combined cusp plication by triangular cusp
      resection and subcommissural annuloplasty. Doppler echocardiography revealed
      trivial aortic valve regurgitation intraoperatively and less than I/IV at
      discharge in all cases. After mean follow-up of 15 months, 2 tricuspid aortic
      valve patients remain I/IV regurgitation and II/IV in the bicuspid patient.
      Although long-term results remain unclear, our results show that this procedure
      is feasible and beneficial in patients with aortic valve regurgitation due to
      cusp prolapse.

PMID- 11305059
TI  - Impending rupture in an aortic arch aneurysm by Candida infection.
AB  - A 68-year-old man was hospitalized with the complaints of left back pain and
      fever. He had a history of using steroids to treat uveitis for about thirty
      years. Computed tomography on the chest demonstrated an impending rupture in an
      aortic arch aneurysm, which was consequently surgically excised. Candida albicans
      was identified in the wall of the aneurysm, so fluconazole and itraconazole were
      administered. The patient was discharged at 120 days after surgery without
      recrudescence of the candida. To our knowledge, this is the fifteenth case of a
      successfully treated aneurysm caused by candida infection.

PMID- 11305060
TI  - Vascular tumor in the mediastinum.
AB  - Mediastinal venous hemangioma is a very rare neoplasm. Here, we describe our
      experience in treating a patient demonstrating such a tumor. The patient, a 23
      year-old man, was admitted to our hospital because of a mediastinal cyst. A
      biopsy of the cystic wall was performed by Video-Assisted-Thoracic-Surgery, in
      April 1999. Clear serous fluid was found in the cyst, and it was thus incorrectly
      diagnosed to be a thymic cyst. The cyst continued to increase in size, and the
      patient began to show an increased temperature after being discharged. A
      resection of the tumor was performed in June 1999. The cyst was filled with
      bloody fluid and, according to the pathological analysis, was diagnosed to be a
      mediastinal venous hemangioma.

PMID- 11305061
TI  - Surgical removal of left atrial myxoma through mini sternotomy and the superior
      transseptal approach.
AB  - A 32-year-old man admitted for treatment of a left atrial myxoma showed a 76 x 25
      mm tumor in the left atrium originating in the interatrial septum upon
      echocardiography. The myxoma was surgically removed using a mini sternotomy and
      the superior transseptal approach. The hospital course was unremarkable. In the 2
      years since operation, the patient has remained asymptomatic and tumor-free. The
      superior transseptal approach is thus useful in surgical removal of left atrial
      myxoma because it can be excised with minimum manipulation despite the mini
      sternotomy and small skin incision.

PMID- 11305062
TI  - Extra-anatomical bypass grafting for coarctation of the aorta associated with
      annuloaortic ectasia. Long-term outcome.
AB  - Two patients each with a rare combination of aortic coarctation and annuloaortic
      ectasia underwent successful single-stage repair in which the aortic root was
      reconstructed with a valved conduit, and an extra-anatomical bypass was made by
      grafting from the ascending to the abdominal aorta. Although the long-term
      outcome of such a long extra-anatomical bypass graft has not yet been
      established, the use of the graft for reducing the risk to coarctation-related
      complications during the early and late postoperative periods appears promising.

PMID- 11305063
TI  - Bland white Garland syndrome with type A aortic dissection.
AB  - We report the case of a 72-year-old patient with a left main coronary artery
      originating from the pulmonary trunk with type A aortic dissection. He is the
      oldest patient among those reported in the literature, operated due to acute type
      A aortic dissection and has survived 4 year after the operation without surgery
      on the coronary artery.

PMID- 11305064
TI  - Pulpal effects of various restorations.

PMID- 11305065
TI  - Acupuncture: a scientific review and clinical applications.

PMID- 11305066
TI  - Implants & periodontal regeneration: how far have we come?

PMID- 11305067
TI  - Superior vena cava obstruction: is stenting necessary?
AB  - No therapy is currently available for patients with recurrent vascular
      obstruction of the superior vena cava (SVC) caused by tumor regrowth after
      chemotherapy or radiation therapy. Intravascular stenting is a new option for the
      treatment of vena cava syndrome. Forty cancer patients with SVC syndrome (SVCS)
      were evaluated by computed tomography (CT) and venography. The SVC or its
      tributaries were stenosed or thrombosed in all patients. The etiology was
      malignant in all but 2 cases: non-small-cell lung carcinoma (n = 28), mediastinal
      nodal metastasis (n = 5), lymphoma (n = 2), pleural mesothelioma (n = 2), small
      cell lung carcinoma (n = 1), and postradiation fibrous mediastinitis (n = 2).
      Stenting was achieved in 39 of the 40 patients, and clinical symptoms subsided in
      92%. Stents remained patent in 36 of these 39 patients throughout a mean follow
      up of 24 weeks (range 3 days to 24 months). SVC stenting is safe, effective and
      allows rapid cure of SVCS and port catheter implantation in patients in poor
      health.

PMID- 11305068
TI  - Prevention of vinorelbine phlebitis with cimetidine. A two-step design study.
AB  - One hundred eighteen patients with various malignancies received a total of 847
      vinorelbine (VNR) infusions, during 25 of which episodes of vinorelbine phlebitis
      occurred (1 in each of the 25 patients concerned). Venous irritation was graded
      with reference to the scale devised by Rittenberg et al. To prevent these 25
      patients against further venous toxicity, we pretreated them with cimetidine 200
      mg i.v. prior to VNR administration in subsequent cycles of chemotherapy. In most
      (19, or 76%) complete prevention of recurrent phlebitis was observed, while
      partial prevention was observed in 5 patients (20%). Treatment was unsuccessful
      in 1 patient. In 127 VNR infusions given after cimetidine prophylaxis only 7 (6%)
      episodes of phlebitis occurred. These data show that i.v. administration of
      cimetidine prior to vinorelbine infusion can successfully prevent recurrence of
      phlebitis in patients who have shown venous irritation upon prior VNR treatment,
      at a rate of 94%.

PMID- 11305069
TI  - The effects of a mindfulness meditation-based stress reduction program on mood
      and symptoms of stress in cancer outpatients: 6-month follow-up.
AB  - The goals of this work were to assess the effects of participation in a
      mindfulness meditation-based stress reduction program on mood disturbance and
      symptoms of stress in cancer outpatients immediately after and 6 months after
      program completion. A convenience sample of eligible cancer patients were
      enrolled after they had given informed consent. All patients completed the
      Profile of Mood States (POMS) and Symptoms of Stress Inventory (SOSI) both before
      and after the intervention and 6 months later. The intervention consisted of a
      mindfulness meditation group lasting 1.5 h each week for 7 weeks, plus daily home
      meditation practice. A total of 89 patients, average age 51, provided pre
      intervention data. Eighty patients provided post-intervention data, and 54
      completed the 6-month follow-up The participants were heterogeneous with respect
      to type and stage of cancer. Patients' scores decreased significantly from before
      to after the intervention on the POMS and SOSI total scores and most subscales,
      indicating less mood disturbance and fewer symptoms of stress, and these
      improvements were maintained at the 6-month follow-up. More advanced stages of
      cancer were associated with less initial mood disturbance, while more home
      practice and higher initial POMS scores predicted improvements on the POMS
      between the pre- and post-intervention scores. Female gender and more education
      were associated with higher initial SOSI scores, and improvements on the SOSI
      were predicted by more education and greater initial mood disturbance. This
      program was effective in decreasing mood disturbance and stress symptoms for up
      to 6 months in both male and female patients with a wide variety of cancer
      diagnoses, stages of illness, and educational background, and with disparate
      ages.

PMID- 11305070
TI  - C-reactive protein and erythrocyte sedimentation rate in differential diagnosis
      between infections and neoplastic fever in patients with solid tumours and
      lymphomas.
AB  - The goals of our work were to study prospectively the possibility of
      differentiating between infections and neoplastic fever in adult cancer patients
      on admission, by means of C-reactive protein (CRP) and erythrocyte sedimentation
      rate (ESR) or of follow-up CRP values. Patients and methods were as follows: the
      final infection group consisted of 56 patients and the noninfection group of 10
      patients with neoplastic fever; CRP was measured on days 0, 3 and 5 and ESR at
      entry. The main results showed that the median CRP did not differ between the
      groups (91 mg/l vs 102 mg/l) on entry, while the ESR level was higher in the
      neoplastic fever group (50 mm/H vs 89 mm/H, P = 0.023). On admission, both
      markers had low area under receiver operating characteristic curves for the
      demonstration of infection (CRP 0.42; ESR 0.27). The CRP level dropped
      significantly in the infection group within 5 days (P = 0.009). We conclude that
      neither of the markers was useful in differentiating between infections and
      neoplastic fever on admission, but that the follow-up CRP values were
      advantageous in this respect.

PMID- 11305071
TI  - Methadone in treatment of tenesmus not responding to morphine escalation.
AB  - Tenesmus is a painful sensation of incomplete evacuation of the bowel and is
      often associated with poorly localized perineal pain. We describe a 68-year-old
      man with locally advanced rectal carcinoma metastatic to lung and with unbearable
      rectal-perineal pain unresponsive to morphine and ketorolac. Treatment with oral
      methadone was successful and pain improved considerably. Methadone has been
      reported to improve pain relief in patients with morphine resistance, and it is
      lipophilic and exerts a lesser activity on opioid receptors in the
      gastrointestinal tract.

PMID- 11305072
TI  - Docetaxel extravasation.
AB  - We report on an accidental extravasation of docetaxel given intravenously as
      chemotherapy in a cancer patient. The extravasate was immediately diluted
      subcutaneously with saline, in addition to which hypothermia (ice-packs) was
      implemented and topical dimethylsulfoxide (DMSO) was applied three times every 45
      min. Corticosteroids and diclofenac were also administered. Dermatitis developed
      immediately but had disappeared within 24 h. Notably, dermatopathological changes
      were absent on days 2-4, minimal on day 5, and increased thereafter. Dermatitis
      developed as a late symptom, resulting in brown discoloration and skin
      hyperplasia. No plastic surgical intervention was necessary. We propose that
      isotonic saline, topical DMSO and local hypothermia may have restricted the
      inflammation and tissue necrosis induced by the extravasation of docetaxel.
      Repetitive topical application of DMSO beyond the day of extravasation had no
      additional benefit.

PMID- 11305073
TI  - Opioids in cancer pain--which one is best?

PMID- 11305074
TI  - Methadone for relief of cancer pain: a review of pharmacokinetics,
      pharmacodynamics, drug interactions and protocols of administration.
AB  - Methadone, a synthetic opioid, has unique pharmacodynamics and pharmacokinetics,
      which contribute to its unique ability to relieve pain unresponsive to other
      potent opiates and its unique dosing and drug interactions. Several guidelines of
      administration have been established. Physicians who are involved in pain
      management should have a fundamental understanding of methadone's unique
      properties.

PMID- 11305075
TI  - Hydromorphone: pharmacology and clinical applications in cancer patients.
AB  - Hydromorphone is a more potent opioid analgesic than morphine and is used for
      moderate to severe pain. It can be administered by injection, by infusion, by
      mouth, and rectally. Oral bioavailability is low. The kidney excretes
      hydromorphone and its metabolites. Some metabolites may have greater analgesic
      activity than hydromorphone itself but are unlikely to contribute to the
      pharmacological activity of hydromorphone. With the exception of pruritus,
      sedation and nausea and vomiting, which may occur less after hydromorphone than
      after morphine, the side-effects of these drugs are similar. On a milligram basis
      hydromorphone is five times as potent as morphine when given by the oral route,
      and 8.5 times as potent as morphine when given intravenously.

PMID- 11305076
TI  - Cancer patients hospitalised for palliative reasons. Symptoms and needs presented
      at a university hospital.
AB  - The aim of this study was to identify patients in need of palliative care in 11
      different care units with a total of 256 beds at Linkoping University Hospital
      and to look at their overall situation with respect to assessed symptom control
      and quality of life. There were 46 patients fulfilling the two criteria of
      incurable cancer and need for palliative care, and each was assessed with the aid
      of a questionnaire (five oral questions on life situation) and a single visual
      analogue scale (VAS) about their overall quality of life (QoL). Each patient also
      assessed him- or herself on the Edmonton Symptom Assessment Scale (ESAS). Total
      ESAS scores ranged from 20 to 639 mm (median 211). Median VAS scores (100 mm =
      greatest symptom severity) were as follows: nausea 6 mm, pain 9 mm, anxiety 17
      mm, depression 18 mm, drowsiness 35 mm, activity 38 mm, appetite 45 mm, and
      sensation of well-being 46 mm. The median score for QoL was 47 and correlated
      well with the total ESAS score. Thirty-seven patients answered the open question
      "What in your current situation troubles you the most?". Seven patients answered
      "nothing", and 10 said "the present symptoms". Twenty patients had different
      concerns (existential, social, and psychological). The low number of hospitalised
      patients found reflects a well-functioning hospital-based home-care unit. Reduced
      appetite, sensation of well-being and activity were dominant, while pain and
      nausea were less intense. The simple QoL-VAS seemed to be comparable to ESAS,
      which is more useful for assessing each single symptom. The non-physical
      dimensions need more attention in the future in order to achieve totally
      satisfactory palliative care.

PMID- 11305077
TI  - Is quantitative ultrasound dependent on bone structure? A reflection.
AB  - Trabecular bone plays a significant role in maintaining bone structural
      integrity. Its density is a significant determinant of bone strength and fracture
      risk, but there is still unexplained variance. It has been suggested that the
      ability to measure structural information will improve the estimation of bone
      strength and fracture risk. Quantitative ultrasound (QUS) is a mechanical wave
      that can be influenced by bone structure, in addition to bone mineral density
      (BMD). This article reviews the evidence in the literature supporting or refuting
      this assumption. Theoretically, the propagation of QUS is influenced by both
      structure and density of the medium. QUS measurement in vivo shows weak but
      significant association with axial BMD. However, the association becomes stronger
      when measured in vitro. Broadband ultrasound attenuation (BUA) exhibits a
      nonlinear relationship with density over a large density range. When cubes of
      cancellous bone are measured in the three orthogonal directions, both BUA and
      speed of sound (SOS) show significant anisotropy which mirrors mechanical
      anisotropy. QUS has also been shown to correlate significantly with structural
      parameters measured by histomorphometry. However, structure remains a significant
      predictor after adjustment for BMD mainly in bovine samples. Other studies using
      phantoms of bone samples have also demonstrated that QUS is dependent on
      structure. There is preliminary indication that fractal dimensions are
      significantly associated with QUS. The ultimate usefulness of structural
      dependence of QUS will be in its ability to improve bone strength estimation
      above and beyond density. There is ample evidence documenting the ability of QUS
      to predict bone strength in vitro. BMD is a significant predictor of bone
      strength and the additive value of structure in estimating bone strength is
      variable. Clinically, ultrasound of the calcaneus is measured in one direction
      (medio-lateral) and the structural variation in this direction may be limited.
      Nevertheless, QUS can provide useful additional information to that provided by
      axial BMD due in part to different precision and accuracy errors and to
      biological discordance. On the whole one could conclude that ultrasound
      attenuation is due to structural parameters and these variables are also
      dependent on density.

PMID- 11305078
TI  - Lifetime and five-year age-specific risks of first and subsequent osteoporotic
      fractures in postmenopausal women.
AB  - We examined the incidence of fragility fractures in Australian women 50 years of
      age and over using a Markov process with Monte Carlo simulations. The lifetime
      risks and the risks of sustaining first and subsequent clinically diagnosed
      fractures at osteoporotic sites were estimated according to age, nursing home
      entry and mortality rates. Hip and spine fractures were evaluated individually
      and fractures of humerus, forearm, wrist, ribs, pelvis, upper leg (excluding
      proximal femur) and tibia/fibula were considered in combination. The model
      predicted that 42.1% of women aged 50 years will sustain at least one fracture in
      their remaining lifetime, of whom half are expected to sustain multiple
      fractures. The lifetime risks of sustaining hip, clinical spine and other
      fractures were 17.0%, 9.6% and 30.4%, with the risks of multiple fractures at
      these sites estimated at 19.5%, 39.7% and 35.7% respectively. The proportion of
      women expected to sustain their first fracture increased from 1.9% of the
      population under 55 years of age up to 49.1% of women over 89 years of age. The 5
      year age-specific risks of sustaining any subsequent fractures increased from
      2.8% of women under the age of 55 years to 61.6% for women age 89 years and over.
      The increased risks of new fractures following a first fracture lead to a
      considerable burden of multiple fractures.

PMID- 11305079
TI  - Vitamin D and bone mineral density in ambulatory women living in Buenos Aires,
      Argentina.
AB  - The aim of this study was to determine possible associations between bone mineral
      density (BMD), 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone
      (PTH). In a retrospective study we examined the case notes of free-living
      postmenopausal women living in our city (34 degrees S). We also report a low
      prevalence of vitamin D deficiency (25(OH)D < 25 nmol/1, 5.6%) and of secondary
      hyperparathyroidism (intact PTH > 65 pg/ml, 7.5%). Age was correlated with BMD at
      the lumbar spine (r = -0.25, p = 0.00038) and femoral neck (r = -0.252, p =
      0.0003). Body mass index (BMI) was correlated with BMD at the femoral neck (r =
      0.177, p = 0.021) but not at the lumbar spine. 25(OH)D was positively correlated
      with BMD at the femoral neck (r = 0.149, p = 0.036) but not at the lumbar spine.
      PTH was positively correlated with age (r = 0.279, p = 0.012) and negatively
      correlated with 25(OH)D (r = -0.322, p = 0.0036). PTH was also negatively
      correlated with BMD at the lumbar spine (r = -0.258, p = 0.02) and the femoral
      neck (r = -0.282, p = 0.011). Forward stepwise multiple regression showed that
      BMI, age and 25(OH)D made significant contributions to BMD at the femoral neck.
      PTH also showed a significant contribution to BMD at both sites. In conclusion,
      weak correlations found between PTH and 25(OH)D and BMD suggest these biochemical
      variables, among other factors, contribute to lumbar spine and femoral neck BMD.

PMID- 11305080
TI  - Quantitative ultrasound of the tibia depends on both cortical density and
      thickness.
AB  - This study investigated whether tibial speed of sound (SOS; SoundScan 2000,
      Myriad Ultrasound Systems, Israel) reflects not only bone mineral density (BMD)
      but also tibial cortical thickness, as assessed by dual-energy X-ray
      absorptiometry (DXA) and Quantitative CT (QCT) at a site-matched location. The
      secondary focus of the study was how tibial SOS compares with BMD at the spine
      and the hip, the most widely used locations for densitometry. Twenty-two young
      normal (N) and 23 postmenopausal women with spinal fractures (Fx) (mean (SD) age
      35 (8) and 70 (5) years) underwent quantitative ultrasound (QUS) SOS measurement
      at the left tibial midshaft. From site-matched QCT scans (three 3-mm slices
      spaced along the QUS measurement region), BMD and cortical thickness were
      computed (QCT-cBMD, QCT-cTh). The cortex in the CT images was then subdivided
      into three concentric and equally spaced bands, and QCT-cBMD was computed
      separately for each band. DXA was performed at the mid-tibia (TIB BMD), at the
      spine (SPINE BMD) and the hip (total hip, HIP BMD). Correlation coefficients
      between parameters were determined with least-square linear fits. Intergroup
      differences were assessed by analysis of covariance, whose r2 value reflects the
      percentage variation in the data explained by group assignment. SOS correlated
      significantly with site-matched parameters (QCT-cBMD, OCT-cTh and TIB BMD, all r
      = 0.6, p < 0.001), SPINE BMD and HIP BMD (both r = 0.5, p < 0.001). Multiple
      regression with both QCT-cBMD and QCT-cTh against SOS yielded r = 0.7 with both
      parameters contributing significantly. For the cortex band subdivision, SOS
      correlated better with QCT-cBMD in the outermost band of the cortex (r = 0.67)
      than with the more central bands (r = 0.59 and r = 0.53). Group assignment could
      best explain SPINE BMD (r2 = 0.62) and HIP BMD (r2 = 0.51). SOS was comparable to
      TIB BMD (r2 = 0.3 vs. r2 = 0.35).: Our findings suggest that the tibial SOS
      measurement depends on both the thickness and density of the tibia, but is more
      strongly influenced by the density of the cortex near the surface than by its
      interior parts. The power of tibial ultrasound to discriminate between normal and
      fracture patients was less than that of spinal and femoral DXA BMD and comparable
      to site-matched DXA BMD.

PMID- 11305081
TI  - The impact of lifestyle factors on stress fractures in female Army recruits.
AB  - Estimates are that stress fractures during basic training (BT) occur in as many
      as 14% of US female military recruits. Injuries of this type lead to morbidity
      ranging from minor pain to serious lifetime disability. Since women are assuming
      an increasing role in the military, this high risk of stress fracture is of
      concern. The purpose of this prospective study was to determine factors that
      predict stress fracture during BT in US Army female recruits. The analysis was
      part of an investigation using quantitative ultrasound (QUS) to determine risk of
      stress fracture during BT. Prior to the start of BT, we obtained QUS measurements
      and asked each subject to complete a risk factor questionnaire. We completed
      assessments for 3758 recruits who then proceeded to 8 weeks of BT, during which
      time any diagnosed stress fractures were reported to us by Army clinicians.
      Stress fractures were confirmed with radiographs. The incidence of stress
      fracture was 8.5% per 8 weeks. Factors associated with stress fracture include:
      QUS, age, race, alcohol and tobacco use, weight-bearing exercise, lowest adult
      weight, corticosteroid use, and, in white women only, use of depo
      medroxyprogesterone acetate (DMPA). Women who fractured were older than women who
      remained fracture-free, and black women were less likely to sustain a fracture
      than whites and other races. Compared with their non-stress-fracture
      counterparts, recruits who developed stress fractures were more likely to report
      current or past smoking, alcoholic drinking of > 10 drinks/week, corticosteroid
      use and lower adult weight. A history of regular exercise was protective against
      stress fracture, and a longer history of exercise further decreased the relative
      risk of fracture. Although current weight was not associated with stress
      fracture, lowest adult weight was inversely related to the risk of fracture. We
      conclude that prevention of stress fractures in female military recruits should
      include a thorough assessment of lifestyle factors such as exercise patterns,
      alcohol and tobacco habits, and corticosteroid and DMPA use. Assessment of risk
      factors may be helpful in pinpointing female recruits who should have further
      evaluation of their bone health or additional preparation, such as gradual
      increases in physical activity, prior to being exposed to the rigor of BT.

PMID- 11305082
TI  - Effects of race on diurnal patterns of renal conservation of calcium and bone
      resorption in premenopausal women.
AB  - Previous studies showed differences in bone and mineral metabolism in African
      Americans and Caucasians: reductions in serum 25-hydroxyvitamin D [25(OH)D],
      urinary calcium and skeletal remodeling and moderate secondary
      hyperparathyroidism. Diurnal studies were carried out in 7 African-American and 7
      white normal premenopausal women matched for age, weight and height to further
      characterize these racial differences in calcium homeostasis. Serum 25(OH)D was
      significantly lower and serum intact parathyroid hormone (PTH) was significantly
      higher in the African-American compared with the white women, whereas serum total
      calcium, Ca2+, phosphorus and 1,25-dihydroxyvitamin D [1,25(OH)2D] were not
      different in the two groups. Serum intact PTH increased significantly at night in
      the white women and did not change in the African-American women. Urinary calcium
      was 47% lower in the African-American than in the white women during the day but
      was not different at night. Urinary calcium declined at night by 53% in the white
      women and by 40% in the African-American women. Stepwise multivariate analysis
      showed that determinants of urinary calcium were mean 24 h serum intact PTH and
      serum Ca2+ in the two groups together, mean 24 h serum intact PTH, body mass
      index (BMI) and serum 25(OH)D in the white women, and BMI in the African-American
      women. Urinary N-telopeptide of type I collagen, a marker of bone resorption,
      increased by over 60% at night in both groups and was 25% lower in African
      American compared with white women, but the difference was not statistically
      different. Urinary free deoxypyridinoline also increased at night in both groups
      and was not racially different. Thus, African-American women show higher serum
      intact PTH and greater conservation of calcium than white women throughout the
      day. In both groups, maintenance of serum calcium at night is achieved by
      increased bone resorption and renal conservation of calcium.

PMID- 11305083
TI  - Reproducibility of DXA: potential impact on serial measurements and
      misclassification of osteoporosis.
AB  - The reproducibility of bone mineral density (BMD) measurements by dual-energy X
      ray absorptiometry (DXA), based on 12 successive monthly determinations, was
      assessed in a group of 24 subjects (23 postmenopausal women, 1 man) using six
      trained operators. The variability (S2A) was calculated from both duplicate
      operator measurements and the standard error of estimate from nonparametric
      regression of the individual subject series. Robust estimates of SA from the 90th
      percentile of the sampling distribution of variances were calculated for the
      spine (25 mg/cm2), femur neck (20 mg/cm2) and total femur (15.5 mg/cm2) using the
      bootstrap technique. The critical difference for a significant decrease (p =
      0.05) at the spine, femoral neck and total femur was estimated at 57, 46 and 36
      mg/cm2 respectively. Estimation of S2A allowed calculation of the probability
      that the true BMD, for an observed BMD near the osteoporosis diagnostic threshold
      (T-score < -2.5), is not misclassified. Analysis of covariance established a
      significant operator-subject interaction at all sites, but only the total femur
      was associated with a significant difference between operators. The percentage of
      body fat was a significant covariate for the spine and total femur regions. ANOVA
      showed that the greater proportion of variance was instrument-related. The
      limitations of DXA as an analytical method are discussed.

PMID- 11305084
TI  - Bone mineral density and quantitative ultrasound parameters in patients with
      Klinefelter's syndrome after long-term testosterone substitution.
AB  - Klinefelter's syndrome (KS) is a common sex chromosomal disorder associated with
      androgen deficiency and osteoporosis. Only few bone mineral density (BMD) and no
      quantitative ultrasound (QUS) data are available in these patients after long
      term testosterone replacement therapy. We examined in a cross-sectional study 52
      chromatin-positive KS patients aged 39.1 +/- 12.4 years (mean +/- SD). Patients
      had been treated with oral or parenteral androgens for 9.2 +/- 8.2 years (range 1
      32 years). Areal BMD and bone mineral apparent density (BMAD, i.e., estimated
      volumetric BMD) at the lumbar spine, total hip and femoral neck were determined
      by dual-energy X-ray absorptiometry. BMD T-scores in the patient group were
      calculated based on three different North American reference databases. The QUS
      parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were
      measured at the calcaneus using an ultrasound imaging device (UBIS 3000) and were
      compared with QUS results in a sex-, age- and height-matched control group. QUS T
      scores were calculated based on the results of QUS measurements in 50 normal
      Dutch men between the ages of 20 and 30 years. QUS and BMD results in the KS
      patient group were compared. Overall, based on the three reference databases, 46%
      and 63% of the KS patients had a T-score between -1 and -2.5 and a further 10%
      and 14% had a T-score < or = -2.5 at the total hip and/or lumbar spine, as
      measured by areal BMD or BMAD, respectively. Thirty-nine percent of the KS
      patients had a T-score between -2.5 and -1, while 2% had a T-score < or = -2.5
      for BUA and/or SOS. BUA (77.7 +/- 15.0 dB/MHz) and SOS (1518.8 +/- 36.5 m/s) were
      significantly lower in the KS patients than in age- and height-matched controls
      (87.1 +/- 17.8 dB/MHz, p < 0.005, and 1536.5 +/- 42.5 m/s, p < 0.05). Correlation
      coefficients between the QUS parameters and areal BMD (0.28 to 0.37) or BMAD
      (0.27 to 0.46) were modest. ROC analysis showed that discrimination of a BMD or
      BMAD T-score < or = -2.5 with either BUA or SOS was not statistically
      significant. Although a limitation of our study is that direct comparison of BMD
      and QUS T-scores is not possible because in the control group in which QUS
      parameters were determined no BMD measurements were performed, we conclude that
      despite long-term testosterone replacement therapy, a considerable percentage of
      patients with KS had a BMD T-score < -1 or even < or = -2.5, based on different
      North American reference databases. This percentage was even higher for BMAD. QUS
      parameters were also low in the KS patient group when compared with Dutch control
      subjects. QUS parameters cannot be used to predict BMD or BMAD in KS patients.

PMID- 11305085
TI  - An interactive tutorial-based training technique for vertebral morphometry.
AB  - The purpose of this work was to develop a computer-based procedure for training
      technologists in vertebral morphometry. The utility of the resulting interactive,
      tutorial based training method was evaluated in this study. The training program
      was composed of four steps: (1) review of an online tutorial, (2) review of
      analyzed spine images, (3) practice in fiducial point placement and (4) testing.
      During testing, vertebral heights were measured from digital, lateral spine
      images containing osteoporotic fractures. Inter-observer measurement precision
      was compared between research technicians, and between technologists and
      radiologist. The technologists participating in this study had no prior
      experience in vertebral morphometry. Following completion of the online training
      program, good inter-observer measurement precision was seen between
      technologists, showing mean coefficients of variation of 2.33% for anterior,
      2.87% for central and 2.65% for posterior vertebral heights. Comparisons between
      the technicians and radiologist ranged from 2.19% to 3.18%. Slightly better
      precision values were seen with height measurements compared with height ratios,
      and with unfractured compared with fractured vertebral bodies. The findings of
      this study indicate that self-directed, tutorial-based training for spine image
      analyses is effective, resulting in good inter-observer measurement precision.
      The interactive tutorial-based approach provides standardized training methods
      and assures consistency of instructional technique over time.

PMID- 11305086
TI  - Ability of peripheral DXA measurements of the forearm to predict low axial bone
      mineral density at menopause.
AB  - The aim of this study was to evaluate the ability of peripheral dual-energy X-ray
      absorptiometry (pDXA) measurement of the forearm to predict low axial bone
      mineral density (BMD) as defined according to the WHO classification. Two hundred
      and thirty-four healthy women aged 45-60 years were investigated. BMD was
      measured at the proximal and distal radius + ulna by pDXA and at the lumbar spine
      and femoral neck by DXA. There was a significant but moderate correlation between
      peripheral and axial BMD measurements, with r values ranging from 0.4 to 0.6
      (SEE: 13.5-17%). The cutoff values for the proximal and distal radius BMD that
      allow the identification with 95% sensitivity of postmenopausal women with either
      a lumbar spine or femoral neck T-score < -1, corresponded to a T-score of +0.5
      (proximal radius) and +1 (distal radius). More than 90% of the whole population
      had a peripheral T-score below these thresholds. Using an axial T-score < or = 
      2.5 as the definition of abnormality reduced to 48% (proximal radius) to 66%
      (distal radius) the number of women who would have required DXA axial
      measurements (i.e., with a pDXA T-score below the cutoff value of -0.7). Of the
      33 women (14%) with a proximal radius T-score < or = -2.5 (osteoporosis), only 1
      had a lumbar spine and femoral neck T-score > or = -1 (normal). Conversely, of
      the 50% (proximal radius) to 65% (distal radius) of the women with normal forearm
      measurement, 5% (proximal radius) to 9% (distal radius) were found to be
      osteoporotic and an additional 57% (proximal radius) to 59% (distal radius) could
      be classified as osteopenic (T-score between -1 and -2.5) at either the lumbar
      spine or femoral neck. In conclusion, use of pDXA forearm measurement as a
      prescreening tool in early postmenopausal women should allow the direct
      identification of about 50% of the women with no axial osteoporosis. However,
      this study highlights the difficulties in using a unique T-score that could be
      applied to different sites to diagnose osteoporosis.

PMID- 11305087
TI  - Mechanical effects on the skeleton: are there clinical implications?
AB  - The basic morphology of the skeleton is determined genetically, but its final
      mass and architecture are modulated by adaptive mechanisms sensitive to
      mechanical factors. When subjected to loading, the ability of bones to resist
      fracture depends on their mass, material properties, geometry and tissue quality.
      The contribution of altered bone geometry to fracture risk is unappreciated by
      clinical assessment using absorptiometry because it fails to distinguish geometry
      and density. For example, for the same bone area and density, small increases in
      the diaphyseal radius effect a disproportionate influence on torsional strength
      of bone. Mechanical factors are clinically relevant because of their ability to
      influence growth, modeling and remodeling activities that can maximize, or
      maintain, the determinants of fracture resistance. Mechanical loads, greater than
      those habitually encountered by the skeleton, effect adaptations in cortical and
      cancellous bone, reduce the rate of bone turnover, and activate new bone
      formation on cortical and trabecular surfaces. In doing so, they increase bone
      strength by beneficial adaptations in the geometric dimensions and material
      properties of the tissue. There is no direct evidence to demonstrate anti
      fracture efficacy for mechanical loading, but the geometric alterations
      engendered undoubtedly increase the structural properties of bone as an organ,
      increasing the resistance to fracture. Like all interventions, issues of safety
      also arise. Physical activities involving high strain rates, heavy lifting or
      impact loading may be detrimental to the joints, leading to osteoarthritis; may
      stimulate fatigue damage leading to stress fractures; or may interact with some
      pharmaceutical interventions to increase the rate of microdamage within cortical
      or trabecular bone.

PMID- 11305088
TI  - Optimal medical management of patients with chronic ischemic heart disease.

PMID- 11305089
TI  - Assays of human postprenylation processing enzymes.

PMID- 11305090
TI  - In vivo prenylation analysis of Ras and Rho proteins.

PMID- 11305091
TI  - Ras interaction with RalGDS effector targets.

PMID- 11305092
TI  - RAS interaction with effector target RIN1.

PMID- 11305093
TI  - Ras and Rap1 interaction with AF-6 effector target.

PMID- 11305094
TI  - Analysis of protein kinase specificity by peptide libraries and prediction of in
      vivo substrates.

PMID- 11305095
TI  - Peptide library screening for determination of SH2 or phosphotyrosine-binding
      domain sequences.

PMID- 11305096
TI  - Expression cloning of farnesylated proteins.

PMID- 11305097
TI  - Expression cloning to identify monomeric GTP-binding proteins by GTP overlay.

PMID- 11305098
TI  - Retrovirus cDNA expression library screening for oncogenes.

PMID- 11305099
TI  - Identification of Ras-regulated genes by representational difference analysis.
AB  - In conclusion, RDA provides a fast, technically simple, and inexpensive way to
      characterize genes aberrantly expressed due to Ras transformation. The
      identification and characterization of these genes may provide insight not only
      into the mechanism by which Ras causes transformation, but also may identify
      novel targets for rational drug design and development of anticancer drugs.

PMID- 11305100
TI  - Differential display analysis of gene expression altered by ras oncogene.
AB  - The goal of the signal transduction pathways, such as those controlled by Ras, is
      in large part to ensure highly stringent regulation of the target genes in the
      nucleus, which are collectively responsible for the signal output, or phenotypes,
      of the cell. Understanding of the Ras effect ultimately requires the
      identification of these downstream target genes. Reverse genetic approaches would
      trace back the pathways by which they are regulated by Ras. While newer methods
      such as DNA microarray are emerging, differential display has allowed the
      identification of a greater number of differentially expressed genes than have
      been cloned by all the other methods combined, based on Medline search. Much of
      this success has been attributed to its simplicity (RT-PCR and DNA-sequencing
      gel) and versatility (compare more than two RNAs for both up- and downregulated
      genes). It has become obvious that finding the genes by either differential
      display or DNA microarray is only the first step toward the understanding of
      biological problems under investigation. It is hoped that finding the right genes
      through careful experimental designs, such as outlined here, will narrow down the
      number of relevant genes and increase the odds for solving the puzzles of nature,
      such as ras.

PMID- 11305101
TI  - cDNA array analyses of K-ras-induced gene transcription.

PMID- 11305102
TI  - Ras signaling pathway for analysis of protein-protein interactions.

PMID- 11305103
TI  - Isolation of effector-selective Ras mutants by yeast two-hybrid screening.
AB  - Ras mutants displaying selective target interactions will often display partial
      loss of function phenotypes when expressed in cells. Thus the isolation of
      mutations in Ras and Ras family members has proved to be a productive approach
      for testing the requirement of specific target interactions to mediate downstream
      responses. The procedures outlined here greatly simplify the isolation of such
      mutants, and it is hoped will contribute to a better understanding of Ras
      effector function.

PMID- 11305104
TI  - Two-hybrid dual bait system to discriminate specificity of protein interactions
      in small GTPases.

PMID- 11305105
TI  - Mammalian expression vectors for Ras family proteins: generation and use of
      expression constructs to analyze Ras family function.

PMID- 11305106
TI  - Functional proteomics analysis of GTPase signaling networks.

PMID- 11305107
TI  - Analyzing JNK and p38 mitogen-activated protein kinase activity.

PMID- 11305108
TI  - Phospho-specific mitogen-activated protein kinase antibodies for ERK, JNK, and
      p38 activation.

PMID- 11305109
TI  - Immunostaining for activated extracellular signal-regulated kinases in cells and
      tissues.

PMID- 11305110
TI  - Dominant negative mutants of mitogen-activated protein kinase pathway.

PMID- 11305111
TI  - Protein transduction: delivery of Tat-GTPase fusion proteins into mammalian
      cells.

PMID- 11305112
TI  - Scaffold protein regulation of mitogen-activated protein kinase cascade.

PMID- 11305113
TI  - Bacterial expression of activated mitogen-activated protein kinases.

PMID- 11305114
TI  - Steroid receptor fusion proteins for conditional activation of Raf-MEK-ERK
      signaling pathway.

PMID- 11305116
TI  - Analysis of pharmacologic inhibitors of Jun N-terminal kinases.

PMID- 11305115
TI  - Pharmacologic inhibitors of MKK1 and MKK2.

PMID- 11305117
TI  - Green fluorescent protein-tagged Ras proteins for intracellular localization.

PMID- 11305118
TI  - Targeting proteins to membranes, using signal sequences for lipid modifications.
AB  - Changing an existing lipid or appending a lipid to a cytosolic protein has
      emerged as an important technique for targeting proteins to membranes and for
      constitutively activating the membrane-bound protein. The potential for more
      precise or regulated interactions of lipidated proteins in membrane subdomains
      suggests that this method for membrane targeting will be of increasing
      usefulness.

PMID- 11305119
TI  - Targeting proteins to specific cellular compartments to optimize physiological
      activity.

PMID- 11305120
TI  - Mapping protein-protein interactions with alkaline phosphatase fusion proteins.

PMID- 11305121
TI  - [Current overview of structural magnetic resonance imaging in schizophrenia].
AB  - Non-invasive morphologic imaging (computer tomography, magnetic resonance
      imaging, MRT) has contributed significantly to our understanding of schizophrenic
      disorders as diseases of the brain. Improved MRT techniques enable us to analyse
      anatomical substructures. The present overview evaluates peer-reviewed MRT
      studies published between 1994 and July 2000 and provides a comparison with our
      own results. Chronic schizophrenic patients most frequently show an enlargement
      in the ventricular system along with a reduction in grey matter. A more detailed
      subdivision into cortical and subcortical regions additionally shows the noted
      volume reduction to be limited to specific areas within the brain rather than
      being distributed equally throughout the brain. Within the area of the temporal
      lobes the two most frequently affected areas are the hippocampus and the gyrus
      temporalis superior. Alterations within these areas correlate with clinical
      symptoms such as hallucinations or thought disorders. Within the frontal cortex
      nearly 70% of all studies show a decrease in overall volume, while 63% note a
      reduction in size within the thalamus and 60% in the cerebellum. Morphologically
      speaking these structures therefore play the greatest role in the pathophysiology
      of schizophrenia and the onset of clinical symptoms. More recent studies also
      showed a specific progression in subgroups of patients pointing toward a
      neurodegenerative process. Additionally there are a number of differential
      antipsychotic effects following longterm treatment with typical neuroleptics as
      compared to atypical antipsychotics. Based on these findings future longitudinal
      studies should examine to what extent such a progressive decrease in volume might
      be influenced by treatment with modern antipsychotics.

PMID- 11305122
TI  - [The physiopathology of weight regulation during treatment with psychotropic
      drugs].
AB  - Weight changes during pharmacological treatment are a well-known phenomenon and
      they have been an object of research since the 1950's. Weight gain occurs during
      treatment with drugs of different chemical structures and is an important problem
      when patients are treated with antidepressants, antipsychotics, or mood
      stabilizers. The clinical relevance of drug-induced weight changes is due to
      increased rates of morbidity and reduced treatment compliance. Regarding the
      underlying causes, the important role of neurotransmitter systems and in
      particular the blockade of serotonin and histamine receptors has been discussed
      since decades. Only recently, however, research has been started on the effects
      of psychotropic agents on major neuroendocrine systems involved in appetite and
      weight regulation. These studies suggest that the fat-cell derived hormone leptin
      might play an important role. Leptin signals to the brain the size of the adipose
      tissue and is probably the most important peripheral signal for the long-term
      regulation of weight. In addition to the neuroendocrine systems, weight gain
      induced by psychotropic agents might also involve immune modulators, in
      particular the proinflammatory cytokine tumor-necrosis-factor-alpha (TNF-alpha)
      and soluble TNF-receptors. Some psychotropic agents influence the TNF system very
      rapidly, already prior to any obvious increases in weight. Hence, changes in the
      TNF-alpha system might be of predictive value for drug-induced weight gain.
      Strategies to minimize or to counteract weight gain induced by psychotropic
      agents include psychotherapeutic and pharmacological approaches. Although
      numerous psychotherapeutic approaches are available, they are only of limited
      usefulness in severely ill psychiatric patients. Fortunately, a number of
      promising pharmacological approaches to reduce weight have been introduced into
      clinical practice during the last years; however, so far there is no knowledge on
      pharmacodynamic and -kinetic interactions with psychotropic drugs, and there is
      no clinical data on the usefulness and safety of such drug combinations.

PMID- 11305123
TI  - [The presentation of disease and medicine in film. Film stereotypes of epilepsy].
AB  - Our presentation examines historical changes in the contextualisation of epilepsy
      by the media. In movies, one may note a particularly long-lasting predominance of
      traditional complexes of the significance of epilepsy. Epilepsy as an hereditary
      disease, as a degenerative illness, as a cause of criminality. These are the
      motifs, established myths, which lived on in movies long beyond the time at which
      scientific opinion had distanced itself from them. A radical change in the manner
      of presentation of epilepsy began in the late sixties. From that time on, not
      only the connotation of epilepsy was altered, but, above all, the presentation of
      the patient, who henceforth, according to the changing processes of society was
      shown as a self-aware and active shaper of his life. Thus it is precisely the
      development during the last fifteen years, in which numerous sensitive motion
      pictures have tackled the inner perspective of the patient, movies having not
      only ceased to pass on the established myths, but become promoters of new
      attitudes toward disease. With this type of representation of disease and
      patient, due to its direct and broad effect, motion pictures can spread new
      realities in a manner hardly possible for other media.

PMID- 11305125
TI  - [Chances and risks for biotechnological Alzheimer's drugs].

PMID- 11305124
TI  - [The psychopathology of delusion, the principle of psychonomy and biological
      theory of delusion].
AB  - The psychopathology of the delusional experiences of schizophrenic patients is
      analyzed on the basis of a sample of 119 drug-naive patients and 502 patients of
      the Bonn-Schizophrenia-Study. The phenomenology, the forms and themes of
      delusion, the delusional certainty, the impact on behaviour
      ("Realitatsbedeutung"), the levels of development of delusional perception and
      the meaning of the psychological working-up of the primordial delusional
      experiences ("Wahnarbeit") are described. The structure-dynamic and the 'gestalt'
      psychological approaches of Janzarik and Kisker try to derive the phenomenon of
      delusional psychoses from the psychonomy of the emotional connections, as far as
      they cannot be explained as immediate symptoms of a somatic illness. [7]. The
      present study also shows that subjective experiences of schizophrenic patients,
      suffering from delusions, largely develop psychonomically according to the rules
      of the psychic motivational dynamic, and that the share of the comprehensible
      working-up and assimilation with regard to the "schizophrenic end-phenomena" [16]
      has been considered too little by the traditional psychiatry. But, there are in
      the view of the basic symptom concept, especially in process active stages, hints
      at a higher share of the somatic component as to the structure of delusional
      syndromes. Looking at the processes, determined by the psychic causality on the
      one side, and at the boundaries of "genetic understanding" [39] in the delusional
      psychosis on the other side, we tried to answer the question to what extent the
      delusional psychosis can be understood according to the "principle of psychonomy"
      [5,6], and, in what respect it seems to be "apsychonomic" and thereby presumably
      somatically founded. The inquiry yields starting points for a biological
      hypothesis of delusion, compatible with a multidimensional conception, that
      reveals understandable connections between delusion and biography and shows the
      reach of the "principle of psychonomy".

PMID- 11305126
TI  - [Use of sentinel networks in the surveillance of infective diseases].

PMID- 11305127
TI  - Correlation between staphylococcal skin infections and sea bathing: a case
      control study.

PMID- 11305128
TI  - The influence of treated sewages on microbiological quality of seawater.

PMID- 11305129
TI  - Effects of a booster dose of tetanus toxoid after different primary courses of
      vaccination: implications on the use of immune globulin.

PMID- 11305130
TI  - [Characterization of sewage treatment plants microflora: contributions of
      molecular biology].

PMID- 11305131
TI  - [Knowledge and behavior regarding prevention and control of biologic risk in
      outpatient care and beauty settings].

PMID- 11305132
TI  - [Mortality in the local health unite of Vallecamonia-Sebino (Brescia) in 1980
      1997: the impact of smoking, alcohol drinking, and traffic accidents].

PMID- 11305133
TI  - [Assessment of the efficacy of disinfectant-impregnated wipes in hand cleaning at
      health care settings].

PMID- 11305134
TI  - [Logistic and organizational support, and proposed private financial intervention
      for the restoration of the Umberto I Polyclinic in Rome].

PMID- 11305135
TI  - [Prevalence of anti-Chlamydia pneumoniae and anti-Helicobacter pylori antibodies
      in subjects with acute myocardial infarction].

PMID- 11305136
TI  - [International recommendations for cardiopulmonary resuscitation].

PMID- 11305137
TI  - [Lesion caused by ischemia-reperfusion in lung transplantation].
AB  - OBJECTIVES: To assess the existence or not of a relation between the
      characteristics of lung donor and/or recipient and the development of ischemia
      reperfusion injury (IRI). We also review the latest experimental findings on the
      biophysical conditions pf graft preservation. PATIENTS AND METHOD: A
      retrospective study of 74 lung transplants performed in our hospital from 1993 to
      1998. Donor and recipient screening and anesthetic and surgical techniques were
      performed following established protocols. Various degrees of IRI were determined
      according to hemodynamic and gasometric criteria. We analyzed the statistical
      relation between donor and recipient variables and IRI. Statistical significance
      was set at p < 0.05. RESULTS: The incidence of IRI was 70.2% (52 cases), with 12
      cases categorized as mild, 22 as moderate and 18 as severe. IRI was significantly
      related only to the start of extracorporeal circulation. CONCLUSIONS: The
      development of IRI in lung transplantation is linked to such donor and/or
      recipient characteristics as the biophysical conditions of graft preservation. At
      present, greater prevention of this type of early dysfunction of the lung graft
      requires not only use of adequate screening criteria for donors and receivers but
      also adequate measures for graft preservation with the use of drugs and handling
      that have been shown to be effective.

PMID- 11305138
TI  - [Immediate anesthesia recovery and psychomotor function of patient after
      prolonged anesthesia with desflurane, sevoflurane or isoflurane].
AB  - OBJECTIVE: To compare the anesthetic maintenance and early postoperative recovery
      and psychomotor function in patients who have been anesthestized with desflurane,
      sevoflurane or isoflurane during prolonged open urological surgery. PATIENTS AND
      METHODS: Seventy-five patients were randomly assigned to receive desflurane,
      sevoflurane or isoflurane with N2O 60% for anesthetic maintenance. The
      concentration of each drug was adjusted to maintain arterial pressure and heart
      rate +/- 20% of baseline. After the operation the anesthetics were discontinued
      and times until eye opening, spontaneous breathing, extubation and orientation
      were recorded. In the post-anesthesia recovery ward we applied the Newman-Trieger
      and Aldrete tests and recorded instances of nausea and vomiting and need for
      analgesia during the first 24 hours after surgery. RESULTS: The groups were
      similar with regard to demographic features, anesthetic maintenance, duration of
      anesthesia and relative doses of the anesthetics used. Recovery times in the
      operating room were significantly shorter (p < 0.05) after anesthesia with
      desflurane and sevoflurane than with isoflurane, with no significant differences
      between the desflurane and sevoflurane groups (duration of anesthesia 198 +/- 90,
      171 +/- 67 and 191 +/- 79; eye opening 7.6 +/- 3.7, 7.8 +/- 3.0 and 11.9 +/- 4.5;
      time until extubation 7.8 +/- 3.0, 8.3 +/- 3.0 and 11.0 +/- 3.5 for desflurane,
      sevoflurane and isoflurane, respectively; all data in minutes). Recovery in the
      post-anesthetic recovery ward was similar for all three groups. CONCLUSIONS:
      Anesthetic maintenance was comparable with all three drugs. Desflurane and
      sevoflurane demonstrated advantages over isoflurane during recovery from
      anesthesia in the operating theater. No significant differences were found in
      psychomotor recovery, nausea and/or vomiting or requirements for postoperative
      analgesia.

PMID- 11305139
TI  - [Impact factor of the Revista Espanola de Anestesiologia y Reanimacion for 1997
      and 1998].
AB  - OBJECTIVES: Revista Espanola de Anestesiologia y Reanimacion (REDAR) is not
      listed in the Journal Citation Reports (JCR) of the Institute for Scientific
      Information (ISI) and therefore REDAR's impact factor (IF) is unknown. This study
      aimed to calculate REDAR's IF and immediacy index for the years 1997 and 1998 as
      well as the IF that the journal would have had if it were considered an ISI
      source journal. The study also aimed to analyze self-citations and how they would
      affect the IF if REDAR were considered a source journal. MATERIAL AND METHODS: We
      calculated the IF and immediacy indexes using ISI methodology, by manually
      counting the references to REDAR articles published in 1997 and 1998 and singling
      out self-citations. RESULTS: The IF was 0.014 for 1997 and 0.054 for 1998. If
      REDAR had been considered a source journal in 1997 the IFs would have been 0.437
      for 1997 and 0.419 for 1998. The immediacy indexes were 0.37 for 1997 and 0.30
      for 1998. The mean number of references per article for the two-year period under
      study was 19.04 with differences depending mainly on type of article. The highest
      numbers of self-citations and the highest proportions of the same were found in
      letters to the editor and authors' replies. The 30 author-plus-journal self
      citations accounted for 9.3% of all self-citations (n = 322). CONCLUSION: The IF
      of REDAR is far lower than those of other European journals. If REDAR were
      accepted as a source journal, it would benefit from its self-citations. Improving
      REDAR's if would result in greater international recognition of our scientific
      level.

PMID- 11305140
TI  - [Lung transplantation and hemophilia. Preoperative considerations].
AB  - Lung transplantation is indicated in certain patients with terminal pulmonary
      disease. We report a case in which a single lung (left) was transplanted to a 16
      year-old girl with hemophilia B; she also suffered idiopathic pulmonary fibrosis
      and had a history of malnutrition, osteoporosis, severe scoliosis, hepatitis C
      positivity and recurrent bilateral pneumothorax. Treatment with pure factor IX
      was started the moment the donor lung was available and was continued for 37 days
      after surgery. Plasma levels of factor IX were kept at 100% during surgery and in
      the early postoperative period, and over 40% after that time. Correct hemostasis
      was thus achieved throughout the procedure, with no need for blood products.
      Patient outcome was satisfactory. The stay in the intensive care recovery ward
      was 17 days and discharge was 40 days after transplantation. We discuss aspects
      of hemophilia and lung transplantation, and the influence on malnutrition,
      chronic steroid treatment and osteoporosis.

PMID- 11305141
TI  - [Preoperative thrombocytopenia with a postoperative diagnosis of thrombotic
      thrombocytopenic purpura].
AB  - A 64-year-old woman came to the emergency room complaining of vomiting and
      abdominal pain; appendicitis was suspected and surgery ordered. A blood work up
      showed a significantly low platelet count (39,000/microliter) and 6 units were
      transfused before surgery. The only observations during surgery were ileitis and
      Meckel's diverticulum. Thrombocytopenia persisted over the first 48 hours after
      surgery in spite of another transfusion of platelets, with worsening awareness
      and acute renal failure. After diagnosis of thrombotic thrombocytopenic purpura
      (TTP), the patient was admitted to the intensive care unit and treatment with
      fresh plasma and corticoids was started. Two weeks later, after complex evolution
      and ten sessions of plasmapheresis, the patient was transferred to the hematology
      ward. TTP must be considered a medical emergency. Platelet transfusions are
      contraindicated, as they can cause serious clinical deterioration. A low platelet
      count before surgery should lead to differential diagnosis to determine the
      cause, with the aim of judging whether platelet transfusion is warranted or not.
      In some etiological processes, such as in the case we report, platelet
      transfusion may be life-threatening; corrective measures must be taken early in
      the process and such transfusion avoided.

PMID- 11305142
TI  - [Intravenous remifentanil, an interesting alternative in obstetric analgesia].

PMID- 11305143
TI  - [The bispectral electroencephalographic index (BIS) and brain death].

PMID- 11305144
TI  - [Degree of compliance with the Recommendations for Testing the Functioning of
      Anesthesia Systems (SEDAR. Spanish Society for Anesthesiology and
      Resuscitation)].

PMID- 11305145
TI  - [Amniotic fluid embolism during the birth process. Apropos of an atypical
      presentation].

PMID- 11305146
TI  - [Headache after dural puncture and headache caused by puncture].

PMID- 11305147
TI  - [Ondansetron in the treatment of the pruritus associated with the spinal infusion
      of opiates].

PMID- 11305148
TI  - [Diagnostic procedures in esophageal diseases].
AB  - The algorithms for diagnosis of esophageal diseases largely depend on the
      patient's symptoms. The most important diagnostic procedure is flexible upper
      gastrointestinal endoscopy which allows inspection and assessment of the entire
      esophagus with the possibility to take biopsies for histological examination.
      Radiographic tests are indicated for special indications only. Finally, the role
      of functional tests (manometry, 24-hour pH-metry) and their indications are
      discussed.

PMID- 11305149
TI  - [Diagnosis and treatment of esophageal motility disorders].
AB  - Apart from gastroesophageal reflux disease, achalasia, non-cardiac chest pain and
      functional dysphagia are the most important manifestations of disturbed
      esophageal motility. Achalasia is characterized by esophageal aperistalsis and
      impaired deglutitive relaxation of the lower esophageal sphincter. The
      morphological correlate is a degeneration of nitrergic neurons in the myenteric
      plexus. Diagnosis is based on barium esophagram or esophageal manometry with the
      latter setting the gold standard. Endoscopic exclusion of a tumor at the
      gastroesophageal junction is mandatory. Appropriate therapeutic interventions are
      pneumatic dilatation or (laparoscopic myotomy) of lower esophageal sphincter. In
      patients unfit for these procedures endoscopic injection of botulinum toxin into
      the lower esophageal sphincter is appropriate. Non-cardiac chest pain may be of
      esophageal origin. Gastroesophageal reflux, spastic motility disorders and
      visceral hypersensitivity are arguable underlying mechanisms. The most important
      diagnostic procedure is 24 h esophageal pH metry correlating symptoms and reflux
      episodes. Proton pump inhibitors and tricyclic antidepressants serving as
      visceral analgesics are appropriate therapeutic approaches. Functional dysphagia
      defines the sensation of impaired passage without mechanical obstruction or a
      neuromuscular disease with known pathology, e.g. scleroderma. Impaired transit is
      proven by esophageal scintigraphy or radiogram both using solid boluses.
      Manometry assesses the underlying mechanisms.

PMID- 11305150
TI  - [Therapy of esophageal diverticula].
AB  - Diverticula of the esophagus can be divided into two categories. Pulsion
      diverticula result from an increased pressure gradient through the upper
      esophageal sphincter resulting in herniation of the mucosa through a weak point
      of the muscle layer. There are two types: hypopharynx (Zenker) diverticulum and
      epiphrenic diverticulum. Traction diverticula result from inflammatory reactions
      in neighboring lymph nodes or as a result of embryonic malformation and are
      composed of all layers of the esophageal wall. The presence of a Zenker
      diverticulum in a symptomatic patient represents always an indication for
      surgical therapy. A successful procedure contains a diverticulectomy combined
      with cervical myotomy. For the treatment of epiphrenic diverticula the underlying
      motility disorder, determined by preoperative manometry, plays a crucial role in
      the length of the myotomy. In order to prevent postoperative reflux a partial
      fundoplication should be added. Independent of location or size surgical therapy
      of diverticula of the esophagus has a success rate of more than 90 percent.

PMID- 11305151
TI  - [Reflux esophagitis--a community-wide increase in incidence].
AB  - Gastroesophageal reflux disease (GERD) is a common disease increasing in
      incidence and prevalence in the industrialised countries. It is a chronic disease
      with a large spectrum of clinical manifestations. The leading symptom is
      heartburn, however the disease may also present with extraesophageal symptoms or
      stay asymptomatic. Motility disorders of the upper GI tract with the key feature
      of impaired LES are the cause for pathologic gastroesophageal reflux in the
      terminal esophagus. The relationship of H. pylori infection with GERD is part of
      the current discussion. The Savary Miller classification for grading of
      refluxesophagitis is now proposed for substitution by the Los Angeles
      classification for the assessment of erosive lesions. Besides complications such
      as bleeding or strictures the main risk is the development of Barrett esophagus
      and adenocarcinoma. Proton pump inhibitors are the therapy of choice for healing
      as well as in longterm therapy and prophylaxis. New endoscopic interventional
      therapies for treatment of GERD and related diseases should be used only in
      controlled studies.

PMID- 11305152
TI  - [Long-term results of conservative management of reflux esophagitis].
AB  - Reflux esophagitis is a frequent and chronic disease. Impairment of the quality
      of life by the reflux symptoms and the risk of complications are the most
      important indications for a long-term treatment. The base of the treatment of
      reflux esophagitis is the inhibition of the gastric acid secretion with proton
      pump inhibitors (PPI) or by H2-receptor antagonist. In general, PPI's are more
      efficient in the treatment of refluxesophagitis as compared to H2-receptor
      antagonists blockers regarding the relieve of symptoms and the healing of erosive
      esophageal lesions. The use of an antacids and procinetics in the long-term
      treatment is not indicated. The treatment strategy depends on the severity of the
      symptoms and the esophageal lesions. Patient with mild esophagitis can be treated
      either with H2-receptor antagonists or with PPI's on demand or continuous. In the
      case of severe esophagitis, a long-term treatment with PPI's is indicated to
      avoid complications. Recurrence of esophagitis during a long-term therapy should
      be treated by PPI's. After healing the long-term treatment should be adapted
      either by increasing the given dose of the medicament or by a switch to more
      effective medicaments in acid suppression.

PMID- 11305153
TI  - [Surgery of reflux esophagitis--a renaissance].
AB  - Gastroesophageal reflux disease (GERD) has a high prevalence of 40% in Western
      countries. A dysfunction of the lower esophageal sphincter of unknown origin is
      the main etiology. Less common pathophysiological reasons are disorders of
      esophageal motility, delayed gastric emptying, gastric acid hypersecretion and
      bile reflux. As causal surgical therapy for these disorders fundoplication has
      been developed 50 years ago. This technique uses a wrap of gastric fundus around
      the distal esophagus as reflux barrier. Because of severe postoperative
      complications (dysphagia, gas bloat syndrome, gastric ulcer) and recurrence after
      fundoplication, medical therapy became the treatment of choice with the
      development of H2-receptor antagonists and proton pump inhibitors in the 1970s.
      However, after improvement of surgical technique and introduction of laparoscopic
      fundoplication in 1991 surgery offers a secure and effective causal therapy.
      Randomized controlled trials proof the superiority of fundoplication versus
      medical therapy in regard of long term results, recurrence and cost effectiveness
      as well as the superiority of laparoscopic versus conventional open
      fundoplication in regard of recovery and cost effectiveness with equal long term
      results. Therefore, laparoscopic fundoplication by an experienced laparoscopic
      surgeon is the surgical therapy of choice. However the high prevalence of GERD
      requires careful selection of patients for surgery. A thorough preoperative
      evaluation including upper gastrointestinal endoscopy with biopsy, esophageal
      manometry and 24 h-pH monitoring as well as upper gastrointestinal contrast study
      is essential. Today the indication for fundoplication is seen in young
      symptomatic patients, requiring a long-term medical therapy, in hiatal hernia
      with threatening complications as well as in complications of severe GERD,
      especially Barrett-esophagus. At present the advantages of total (Nissen) or
      partial (Toupet) wrap as well as the benefit of dissection of the short gastric
      vessels for total fundoplication are still unclear, especially concerning long
      term results. To answer these technical questions further randomized controlled
      trials with long-term follow-up have to be performed.

PMID- 11305154
TI  - [Barrett's esophagus: screening and prognosis].
AB  - The diagnostic criteria for Barrett's disease have changed very considerably
      during the last 10 years. Classically, the definition asked for columnar
      epithelium in the lower esophagus extending for at least 3 cm proximally. Now,
      the diagnosis rests on the finding of specialised intestinal metaplasia, i.e.
      columnar epithelium with goblet cells, in the esophagus, regardless of the
      extension. This is important because it is this type of metaplasia that is
      associated with an increased risk for the development of esophageal
      adenocarcinoma and esophageal adenocarcinoma is the tumor with the fastest rising
      incidence in the western world in recent years. The criteria of the current
      definition of Barrett's esophagus are described in detail and the implications
      this change in definition carries for screening and surveillance of patients is
      discussed.

PMID- 11305155
TI  - [Staging and neoadjuvant therapy of squamous cell carcinoma of esophagus].
AB  - Once the diagnosis of esophageal cancer is established, the decision on treatment
      will depend on the stage of the disease. Since improvement of prognosis can only
      be expected in patients with complete removal of their tumor, preoperative
      staging plays a pivotal role in the decision-making process. Preoperative
      diagnostic procedures should define the tumor in its relation to the tracheal
      bifurcation (site), determine the depth of tumor invasion (T status), evaluate
      regional lymph node metastases (N1 disease) and exclude distant metastases (M1
      disease). Endosonography represents currently the most accurate imaging technique
      for detecting the correct T stage over the correct N stage. A higher accuracy
      rate may be achieved by combining endosonography with other staging modalities
      such as computed tomography. Chest x-ray, and percutaneous ultrasonography
      (abdominal, neck) form the diagnostic basis in staging M1 disease. Computed
      tomography (neck, chest and abdomen) is currently the best method to detect
      metastases in the liver and in celiac nodes. Staging laparoscopy when combined
      with laparoscopic ultrasonography shows a higher sensitivity than ultrasonography
      and computed tomography in the diagnosis of smaller metastases and peritoneal
      seedings. En bloc esophagectomy together with the regional lymph nodes remains
      the treatment of choice in medically fit patients with localized esophageal
      carcinoma (Stage I-IIB, T1-T2/N0-N1/M0). Due to early involvement of mediastinal
      structures, curative resection is unlikely to be achieved in patients with
      locally advanced esophageal carcinoma (Stage III, T3-T4/N0-N1/M0). Most available
      data indicate that neoadjuvant radiochemotherapy leads in a significant number of
      patients to downstaging of the tumor, increases the rate of R0 resection,
      improves local tumor control, and prolongs the recurrence free interval. However,
      neoadjuvant radiochemotherapy resulted in a marked increase of morbidity and
      postoperative mortality without improvement of survival. At present, neoadjuvant
      therapy is still experimental and there is no consensus for an optimal treatment
      regimen. Its use outside of an investigational setting can not be recommended.
      Future research must focus on more effective and less toxic neoadjuvant
      modalities (e.g. new chemotherapy agents, hyperthermia).

PMID- 11305156
TI  - [Modern surgical treatment of esophageal carcinoma].
AB  - Curability of esophageal cancer has increased significantly during the last two
      decades by inducing stage adapted multimodal treatment strategies and radical
      resections. This overview summarizes advantages and disadvantages of various
      operative approaches, the extend of resection and methods to substitute the
      esophagus.

PMID- 11305157
TI  - [Therapy refractory depressive episode in bipolar disorder caused by primary
      hyperparathyroidism].

PMID- 11305158
TI  - [The new subjectivity].

PMID- 11305159
TI  - [Addiction as a life style: on the social anthropology of addiction].
AB  - Regularly the unsolved problems of addiction- and dependence-research are
      discussed in the sense of the psycho-body-dichotomy, arguing that the biological
      mechanisms of reward-systems and their pathobiochemistry have to be confronted
      with the psychological and philosophical/anthropological dimensions within
      persons. The present paper, however, tries to demonstrate that this dichotomy is
      insufficient insofar as social-anthropological components of being addicted,
      which represent integrative constituents of a theory of addiction, are neglected
      within such a scheme. The developmental-psychological and philosophical
      psychological aspects of socialization are considered and related to internal
      valuating systems and reality models regarding the problems of drugs and
      dependency. Herein it is shown that especially the model of Rene Girard,
      constituting "mimetic triangulation", is applicable to the understanding of the
      microsocialization of drug-consumers. This is also demonstrated in film-examples.
      It is shown that the problem of drug-addiction cannot be solved from a
      neurobiological/biochemical--and also a psychotherapeutic/psychoanalytic concept-
      without incorporating the dynamics and the value-worlds within groups which
      should also be considered to be therapeutically influenceable.

PMID- 11305160
TI  - [Cognitive dysfunction in schizophrenic psychoses. Drug and psychological
      treatment choices].
AB  - Primarily from the perspective of psychopharmacology, schizophrenic
      symptomatology has recently been dichotomized into "plus" and "minus" symptoms,
      although the role of cognitive dysfunctions has been regarded as particularly
      important for the diagnosis since the time of Eugen Bleuler. Many studies show
      that schizophrenic patients suffer consistently from cognitive dysfunction. Among
      these, are impairments of attention and memory functions as well as executive
      functions such as planning and problem solving. These impairments are stable or
      progressive and often continue into the remission phase of schizophrenia and
      impair both social integration as well as occupational performance. In this
      overview, research results on cognitive dysfunction in patients with
      schizophrenic illnesses and their relation to psychosocial disabilities are
      described first. The therapeutic value and possible clinical-practice
      implications of atypical anti-psychotics and various cognitive therapy methods
      are then presented. Methodological weaknesses and open questions, both
      pharmacological and with regard to cognitive interventions, are discussed.

PMID- 11305161
TI  - [Developing a cooperation model between 3 psychiatric clinics with the goal of
      quality assurance in mandatory treatment exemplified by restraint documentation].
AB  - Since 1996 three psychiatric hospitals have been working together closely in a
      team aiming at improving the quality management of coercive measures. The first
      comparison of documented restraints showed conspicuous differences in incidence
      and duration. Due to this, the group decided to document and to compare the
      incidence, duration and reason of restraints and the legal status and
      sociodemographic variables in the three hospitals over one year. Considerable
      deviations were found with regard to the number and duration of restraints and
      number of patients concerned. Hospital A (2622 admissions) registered 103
      restraints of 53 persons whereas hospital B (5802 admissions) reported 254
      restraints of 121 persons, hospital C (4252 admissions) finally, documented 621
      restraints of 120 persons. Hypotheses giving reason for these findings are
      discussed. Furthermore, developments and changes aiming at reducing coercive
      measures and at complete and comparative documentation by co-operation of the
      three hospitals, are reported.

PMID- 11305162
TI  - [How do mentally ill homeless persons evaluate their quality of life].
AB  - Besides pronounced deficiencies in psychiatric research concerning homeless
      mentally ill in Germany, studies concerned with the quality of life of homeless
      mentally ill were missing until now. This study reveals in a representative
      sample of 102 homeless people from the City of Mannheim, Germany that--compared
      to the homeless without psychiatric disorders of the sample--the mentally ill
      homeless (prevalence 68.6%) have significantly different subjective views of
      their quality of life regarding the items "state of health", "physical
      capabilities" and "support from others". The differences were even stronger if
      the homeless mentally ill were compared to a group of non-homeless mentally ill
      schizophrenic patients (n = 104), cared for in the City's well-equipped community
      care services. Community care patients reported a significantly better quality of
      life in respect of 11 items. These results were seen as a success of the concept
      of community-based mental health care. The consequences for improving care
      strategies for homeless mentally ill are discussed.

PMID- 11305163
TI  - [Evaluation of a special project for treatment of psychiatrically ill Turkish
      migrants].
AB  - The in-patient treatment of migrants with psychiatric disorders causes particular
      difficulties. There is often a barrier of language and culture that raises
      problems for the diagnostic and therapeutic process. To solve these problems we
      developed a bilingual setting by integrating a Turkish psychologist who belongs
      to a counselling centre into our therapeutic team for at least once a week. This
      offers the possibility for a very qualified psychopathological assessment as the
      patient can talk to the Turkish psychologist in his native language and the
      Turkish psychologist can translate this and his own impression accurately also
      using the psychiatric language. All relevant themes can be discussed, including
      the possibility of continuing the therapy in the counceling centre. We
      investigated the impact of this kind of therapeutic approach on the duration of
      hospitalisation, remission in terms of psychopathology, rehabilitation level,
      ratio of readmission and contentment with therapy. The migrants were divided into
      two groups: Turkish migrants were treated in this special setting, non Turkish
      migrants were not treated in the manner described. There are shorter periods of
      hospital treatment for Turkish non-schizophrenic in-patients and Turkish
      schizophrenic patients achieve higher levels of rehabilitation. Turkish patients
      with all kinds of psychiatric diagnoses show lower ratios of readmission and
      express greater contentment with therapy. The psychopathological symptoms
      themselves, however, are not substantically reduced in this special setting.

PMID- 11305164
TI  - ["Lex Kendra" in New York, United States. Homicide, "revolving door psychiatry"
      and political response].
AB  - OBJECTIVE AND METHODS: The history, motivation and consequences of the New York
      State "Kendra's Law" as of August 1999 are reviewed. RESULTS: "Kendra's Law" was
      the consequence of the killing of a young woman, Kendra W., by a schizophrenic
      patient later convicted for second degree murder. Before, he had been repeatedly
      rejected when he sought treatment in state-run psychiatric facilities and was
      expelled several times from long-term hospitals despite a long history of violent
      behaviour when untreated. "Kendra's Law" now entitles physicians, case workers,
      roommates and families of untreated mentally ill persons to seek a court order
      forcing a patient to comply with treatment and, at the same time, compelling
      mental health institutions to grant this treatment. Additionally, the law and
      another bill signed in November 1999 provided for additional funding for the
      underfinanced state-run mental health system. CONCLUSION: "Kendra's Law"
      illustrates a bidirectional attempt to cope with the revolving door treatment
      situation of mentally ill in the State of New York by additional funding and
      additional possibilities to enforce treatment. The law illustrates the
      fundamental conflict between individual autonomy and the need for treatment of
      people suffering from severe mental illness.

PMID- 11305165
TI  - [Beyond "successful aging: Rembrandt in his self-portraits].
AB  - The process of aging has been generally associated with cognitive dedine.
      However, some complex cognitive abilities, such as wisdom and judgement, have
      been suggested to improve with age. In the current study, the development of an
      advanced artistic ability is examined over the life span of Rembrandt H. van
      Rijn. Analysis of the paintings revealed the development of an old-age-style in
      the last portrait, characterised by uniformity of texture, facture, and lighting.
      The self-portrait painted in the last year of Rembrandt's life reflects a high
      degree of integration of artistic skill and experience gathered in the course of
      life, and hence reflects features of wisdom in the sence suggested by Baltes. The
      development of a mature "late" style can help to characterise the emergence of
      qualitatively different and advanced cognitive abilities in old age.

PMID- 11305166
TI  - [Attitude of the elderly to the etiology of memory disorders].
AB  - PURPOSE: The early recognition of dementia assumes increasing importance. Lay
      beliefs on the causes of loss of memory play a major part in this regard as they
      have shown to determine help-seeking behaviour. METHOD: 720 persons aged 75 or
      older were questioned on their beliefs on the causes of cognitive deficits in the
      context of the Leipzig Longitudinal Study of the Aged (LEILA 75+). RESULTS:
      Almost one-third of the respondents mentioned exclusively biological causes,
      vascular lesions coming first. One quarter of those questioned ascribed memory
      deficits to non-biological factors. Every tenth person suspected that they result
      from a combination of both. One quarter of the elderly did not know any answer.
      DISCUSSION: The results are contrasted with outcomes of epidemiological dementia
      research. It is argued that increasing and better quality information of the
      public are urgently required.

PMID- 11305167
TI  - [How do geriatric psychiatry patients evaluate their stay in a specialized
      psychiatric department of a general hospital?].
AB  - PURPOSE: Following mainly the patients' view, the study examines whether the
      treatment of gerontopsychiatric patients in common with younger patients in a
      general psychiatric ward might entail disadvantages. METHOD: Out of a total of
      297 gerontopsychiatric patients treated in 1999, a group of 107 patients was
      asked via a self-constructed questionnaire about different aspects of common
      treatment with younger patients. RESULTS: With the exception of an
      underrepresentation of organic disorders, the 107 interviewed patients did not
      differ substantially in basic characteristics from the entire group of
      gerontopsychiatric patients treated in 1999. Life together with younger patients
      was judged predominantly positively. The older patients themselves rejected the
      often stated complaint that nurses would neglect the gerontopsychiatric patients
      on age-mixed wards. CONCLUSIONS: Neither objective facts nor the subjective
      judgement by the users point to assume that common treatment of
      gerontopsychiatric patients together with younger patients could be
      disadvantageous. The contrary seems to be the case.

PMID- 11305168
TI  - [Kleptomania in frontal lobe lesion].
AB  - A case of a kleptomaniac with frontal lobe dysfunction is presented. Kleptomania
      is related to the obsessive-compulsive spectrum disorders and the affective
      spectrum disorders. In obsessive-compulsive spectrum disorders neuroimaging and
      neuropsychological tasks have revealed abnormal functioning in the frontal brain
      which also could be related to kleptomania. Consolidated findings from animal and
      human studies have implied central serotonergic transmission in the genesis of
      obsessive-compulsive spectrum disorders and affective spectrum disorders.
      Altogether, these results suggest that kleptomania, like other disorders of the
      above mentioned spectrums, could have an abnormality in serotonergic transmission
      in common.

PMID- 11305169
TI  - [Financial development of the Munich General Hospital 1830-1894].
AB  - The Munich General Hospital is typical for the modern hospital developing in the
      late 18th century. Before the introduction of the compulsory Imperial Health
      Insurance in 1884 in many southern states of Germany municipals installed some
      kind of insurance system to take care for their poor. These insurance systems
      were intended to provide hospital care for the lower classes and give the
      hospital a new source of income. The Munich General Hospital has been founded in
      1813 and a voluntary insurance scheme was installed. This paper examines the
      financial development of the Munich General Hospital in the long run through
      studying its expenditures and sources of income from 1830/31 until 1894.
      Especially the effects of the various kinds of insurance schemes from the first
      voluntary insurance system (1813) until the compulsory Imperial Health Insurance
      (1884) on the hospital's financial capacity have been analysed. Until the 1830s
      the hospital struggled with serious financial problems because the founding fund
      was too small for the high number of non-paying patients. This situation was
      aggravated through the failure of the first insurance system which was
      subsequently reformed in 1832. With the new mandatory insurance scheme and the
      revenues of the founding fund the hospital reached in the following decades a
      high level of independence from traditional financing sources such as donations
      and public subsidies. The compulsory Imperial Health Insurance reinforced this
      trend. In consequence the hospital did not need any municipal subsidies to
      finance its regular expenditures.

PMID- 11305170
TI  - [Earth magnetism research in the 19th century].
AB  - Even before the discovery of the electromagnetism by Oersted, and before Ampere,
      who attributed all magnetism to the flux of electrical currents, A. v. Humboldt
      and Hansteen had turned to geomagnetism. With the help of the "Gottinger
      Magnetische Verein", a worldwide cooperation under the leadership of Gauss game
      into existence. Even today, Gauss' theory of the geomagnetism is one of the
      pillars for geomagnetical research work. Thereafter, J. v. Lamont, Prof. in
      Munich, took over the leadership in Germany. In England, the Magnetic Crusade was
      started by the initiative of John Herschel and E. Sabine. At the beginning of the
      forties, James Clarke Ross advanced to the Antarctic Continent, which was then
      quite unknown. Ten years later, Sabine was able to gather solar-terrestrial
      relations from the data of the colonical observatories. In the eighties, Arthur
      Schuster, following Balfour Stewart's ideas, succeeded in interpreting the daily
      variations of the electrical process in the high atmosphere. The geomagnetic
      research work in Germany was given a fresh impetus by the First Polar Year 1882
      1883. Georg Neumayer, director of the "Deutsche Seewarte" in Hamburg, had been
      one of the initiators of the Polar Year. He had a close cooperation with the
      newly founded "Kaiserliches Marineobservatorium" in Wilhelmshaven, and he also
      managed to gain the collaboration of the "Gauss-Observatorium fur Erdmagnetismus"
      in Gottingen under E. Schering. In the Polar Year, the first automatic recording
      magnetometers (Kew-Model) were used in a German observatory in Wilhelmshaven.
      Here M. Eschenhagen, who later became director of the geomagnetic section in the
      new Meterological-Magnetic Observatory in Potsdam, gained special merit. The
      treatise considers preceding hypotheses of geomagnetism as well as the
      palaeomagnetic studies. The essential seismological investigations at the turn of
      the 19th to the 20th century are briefly treated. They represent one of the
      keystones for the modern theory of the Earthdynamo.n

PMID- 11305171
TI  - ["I would like to so much--but then also; but, but--!!!"--torment of a private
      lecturer at the beginning of the 19th century].
AB  - The biography of Carl Friedrich August Theodor Kastner (1797-after 1841), the
      brother of the famous chemist and teacher of Justus von Liebig (1803-1873) Karl
      Wilhelm Gottlob Kastner (1783-1857), is an interesting example of the difficult
      situation of outside lecturers at the universities in the first half of the 19th
      century; a big group of scientists, which are absolutely underrepresented in the
      source material and in the historiography too. This paper tries to show the facts
      and the backgrounds for the problems in the career of outside lecturers.

PMID- 11305172
TI  - [The Darmstadt Johannes Alexandrinus fragment].
AB  - Three latin fragments (about 1050), included in the envelope of a manuscript,
      written about 1530 in Cologne, could be identified as parts of the latin version
      of an Alexandrian commentary (probably written by Johannes Alexandrinus) on
      Galen's book 'De sectis'. C. D. Pritchet edited this text in 1982, but he thought
      that he was printing a translation of this commentary on Galen's book, written by
      Burgundio de Pisa in the year 1185. By means of an exact comparative analysis of
      the fragments with Galen's original Greek text, we were able to show that these
      fragments offer almost the same text as Pritchet. But it is remarkable that there
      are some differences between our version and the text of Pritchet. It seems that
      our version proves the existence of an until now unknown medieval revision of the
      Galen-commentary by Johannes Alexandrinus.

PMID- 11305173
TI  - The perfect physician: 16th century perspectives from the Iberian peninsula.

PMID- 11305174
TI  - [Signa mortui foetus--the dead fetus in the uterus. A new text of medieval
      gynecology].

PMID- 11305175
TI  - [Urban mobility and air quality: impact of the opening of the new Lecco cross
      ways on air pollution].

PMID- 11305176
TI  - [Experimental evaluation of natural air exchange in different indoor
      environments].

PMID- 11305177
TI  - [Risk of repetitive strain associated with occupational activities at building
      sites].

PMID- 11305179
TI  - [Health-hygiene building regulations in the Ticin Canton].

PMID- 11305178
TI  - [Health-hygiene aspects and implications of township urban planning].

PMID- 11305180
TI  - [Enforcement of D.Lgs. 626/94 in biotechnology areas of work: analysis based on a
      sample of public workers].

PMID- 11305181
TI  - [Partial recycling air conditioning system: project and technology].

PMID- 11305182
TI  - [Consistency between grades based on multiple choice written tests and oral
      examination: the experience with environmental hygiene exam].

PMID- 11305183
TI  - [What is your diagnosis? Meningococcal infection].

PMID- 11305184
TI  - [Treatment of metastasized malignant melanoma].
AB  - The prognosis of stage IV melanoma is unfavourable compared to the curative
      surgical results in early stage. The median survival amounts to 8-10 months and
      only 1-2% of the patients will not relapse. Dacarbazine remains the reference
      standard treatment for metastatic melanoma. The modest activity of chemotherapy
      in stage IV has prompted investigators to consider combinations of multiagent
      chemotherapy, immunotherapy and biochemotherapy. Promising treatment options are
      melanoma vaccines to obtain an efficient immunoresponse, the combination of
      chemotherapy with Interleukin (IL)-2 and Interferon alfa (IFN-alpha) as a way of
      improving response rates and survival.

PMID- 11305185
TI  - [Radiotherapy of malignant melanoma of the skin].
AB  - The malignant melanoma is presently regarded as a radiosensitive tumor. Usually
      the first choice treatment for primary melanomas is surgery. However, we regard
      operation and radiotherapy of primary melanomas of the face up to a thickness of
      1 mm as equal therapeutic methods in patients who are sixty years and older.
      Radiotherapy can be recommended for primary melanomas of the face with higher
      tumor thickness or in younger patients if a major operations is too burdensome
      due to impaired general health or internal diseases or if the patient refuses the
      operation. Radiotherapy of primary melanomas of the scalp can be considered if
      the patient can accept the irreversible hair loss in the irradiated field. Soft x
      ray therapy with single doses of 3.5-5 Gy 3-6 times weekly and total doses of 80
      Gy for invasive primary melanomas and 70 Gy for in-situ melanomas has been
      effective. We choose a half value depth of at least 2.8 mm. The safety margin are
      1 cm for in-situ melanomas, and for invasive primary tumors it should be the same
      as used in surgery: 1 cm for < or = 1 mm, 2 cm for 1-4 mm and 3 cm for > or = 4
      mm thick lesions. Prior to soft x-ray therapy the diagnosis should be confirmed
      and the tumor thickness determined by a representative biopsy. If possible,
      nodular parts of the tumor should be totally excised. The subsequent soft x-ray
      therapy can then be performed with a minor half dose depth. Smaller primary
      melanomas may be totally excised before radiotherapy so that only the safety
      margin has to be irradiated. Pigment may be visible in the irradiated field up to
      one year after the end of radiotherapy. Melanoma metastases can be treated by
      radiotherapy if they grow rapidly or cause symptoms. Pain due to bone metastases
      is relieved or totally eliminated by this treatment. Excessively high single
      doses are not necessary for the radiotherapy of melanoma metastases. An adjuvant
      radiotherapy after excision of regional lymph node metastases does not influence
      the overall survival and the local recurrence rate and can therefore not be
      recommended.

PMID- 11305186
TI  - [New aspects of immunotherapy of malignant melanoma].
AB  - Malignant melanoma is a fatal disease in its terminal stage. Despite of all
      attempts to prolong the life of the patient with chemo- or chemoimmunotherapies,
      the course of the disease is rarely affected. Specific immunotherapies with
      antigen-pulsed DC might be a reason for optimism. DC are professional antigen
      presenting cells with a capability to process and present melanoma antigens.
      First vaccination studies show encouraging results with complete remissions even
      in progressed cases.

PMID- 11305187
TI  - [Medicine on the internet: information highway or maze?].

PMID- 11305188
TI  - [Epidermoid cyst of the end phalanx].

PMID- 11305189
TI  - [Injury due to human bite].

PMID- 11305190
TI  - [Reliable sun protection with high light protection factor decreases the rate of
      new pigment cell nevi in school children, especially in children with sensitive
      skin or with freckles].

PMID- 11305191
TI  - [Present limitations of molecular biological diagnostics in Gillespie syndrome].
AB  - BACKGROUND: Gillespie syndrome is the phenotype partial aniridia, cerebellar
      ataxia and mental retardation. Further malformations can be associated, mainly
      females are affected. Inheritance and genetics of the syndrome are unknown.
      Autosomal dominant aniridia is an important differential diagnosis of fixed
      dilated pupils and is usually associated by mutations of the PAX6 gene. In 1998
      the first report of a chromosomal abnormality presenting a de novo translocation
      t(X;11) (p22.32;p12) detected in a patient with Gillespie syndrome has been
      published. PATIENTS AND METHODS: A 8 year-old girl with Gillespie syndrome
      phenotype associated with congenital pulmonary stenosis and helix dysplasia is
      reported. Karyotyping as well as molecular biological investigations of the PAX6
      gene were performed. RESULTS: The karyotype of the girl and her clinically
      inconspicuous mother showed no abnormalities, especially no de novo translocation
      of the chromosomes X and 11. PAX6 gene analysis of the affected girl presented no
      mutations. CONCLUSIONS: The combination of muscular hypotonia and fixed dilated
      pupils in infancy is suspicious of Gillespie syndrome. Congenital pulmonary
      stenosis and helix dysplasia can be associated. PAX6 gene analysis can be helpful
      to distinguish between autosomal dominant aniridia and Gillespie syndrome. To
      illucidate the underlying genetic defects karyotyping and the search for de novo
      translocations especially of chromosome X and 11 should be performed.

PMID- 11305192
TI  - [Circumcision--criticism of the routine].
AB  - Circumcision is one of the most frequent operative procedures done in males.
      About 120 circumcisions are performed every 5 minutes over the world [14]. Three
      different reasons lead to circumcision: 1) Medical reasons in present of a
      pathologic phimosis. 2) Circumcisions done due to religious, social or cultural
      rea-reasons. 3) Finally in many countries circumcision is performed as "routine
      circumcision" in the newborn period. While in the United States the number of
      routine-circumcisions decreases (about 60% of all male newborns) South-Korea has
      a rate near to 100%. Even with no religious or cultural background in Germany
      circumcision often is performed without scrutinizing medical indication.
      Circumcision is regarded as an procedure with no complications and no
      disadvantage for the patient. In general circumcision has no medical benefit
      neither in decreasing the incidence of urinary tract infections nor of sexual
      transmitted diseases nor of neoplasias. Medical indication for circumcision is
      given in present of pathologic phimosis in 4% of all males. Postoperative
      complications range up to 2% and "circumcision is the amputation of the prepuce
      from the rest of the penis, resulting in permanent alteration of the anatomy,
      histology and function of the penis...". There are many reports about having
      discomfort and disadvantages after circumcision as well to the males as to the
      sexual partners. This challenge the legality of neonatal involuntary circumcision
      because legality is based on saving the children's best interests.

PMID- 11305193
TI  - [MRI follow-up study of aseptic osteonecrosis (AON) in children treated with
      chemotherapy for malignant diseases].
AB  - PURPOSE: The aim of the study was to evaluate by MRI the course of aseptic
      osteonecrosis (AON) after chemotherapy in children with different malignancies.
      MATERIAL AND METHODS: Retrospective analysis of 72 MRI studies in 20 children
      (age: 3.2-18.4 years) presenting with AON after chemotherapy. 8 children were
      treated exclusively with relief of weightbearing structures, whereas 12 children
      were additionally treated with hyperbaric oxygen therapy (HBO). Within a range of
      3-76 months each patient received 1-6 follow-up exams. The acquired series
      included multi planar spin-echo as well as fatt-suppressed inversion recovery
      sequences. The MRI examinations were evaluated by a point-score system (1-6) by
      two radiologists. RESULTS: AON was most commonly seen in the pedal bones (26.4%),
      in the hip (23.6%), and in the knee joints (19.4%). Initial findings revealed an
      average score of 3.1 points. Based upon these initial findings, subsequent
      analyses show a statistically significant (p < 0.05) score increase of 0.6 score
      points. For the observed intervals a: < 6 months, b: 6-12 months, and c: > 12
      months the mean scores were: a: 3.3, b: 3.7, and c: 4.5 points. During the
      observed time period 5 patients were surgically treated in the affected bone
      areas. CONCLUSION: The majority of chemotherapy associated AON which initially
      present with advanced findings showed in MRI a progression with frequent
      destruction of the joint surface over their further course. More discrete forms
      of AON, especially osteoedema, can be positively influenced by conservative
      therapy.

PMID- 11305194
TI  - [Intrauterine herpes simplex virus infection].
AB  - BACKGROUND: Early fetal herpes simplex virus (HSV) infection is rarely
      documented. Only the minority of affected fetuses survive this condition. PATIENT
      AND METHODS: At 19 weeks of gestation the first episode of a genital HSV
      infection of a pregnant woman was treated with local interferon beta. At 34 weeks
      of gestation hydrocephalus with secondary microcephaly and microphthalmia of both
      eyes was detected by ultrasonography. In the amniotic fluid HSV type 2 (HSV-2)
      was isolated and HSV-2-DNA was detected by PCR. The serum of the mother proved
      positive for HSV-2 (glycoprotein G2)-specific IgG-antibodies. No other infectious
      causes were apparent on further testing. At 35 + 4 weeks gestation a small-for
      gestational-age neonate (2130 g) with microcephaly (29 cm head circumference) was
      born by spontaneous vaginal delivery. Scarce ulcerative skin lesions and
      vesicles, hepatosplenomegaly and microphthalmia were diagnosed. Furthermore,
      encephalomalacia with parenchymal destruction, cataract of both eyes and aplasia
      of the maculae and papillae were found. HSV-2-PCR was tested positive in
      chorionic cells and an umbilical segment of the placenta as well as in swabs from
      both eyes, throat, and a herpetic skin lesion collected during the first 5 days
      of life. HSV-IgM-antibodies were found in the umbilical cord blood. Local and
      intravenous treatment with aciclovir was started. The infant exhibited signs of a
      severely malfunctioning central nervous system. At the age of 4 months the boy
      suffered from generalised cerebral seizures. He died at the age of 9 months as a
      consequence of respiratory insufficiency with consecutive circulation failure.
      RESULTS: The case of an intrauterine HSV-2-infection is presented. The time of
      onset of fetal infection was most probably at the time of the maternal disease
      (19 weeks of gestation). Inspite of the very early infection the fetus did not
      die in utero. CONCLUSIONS: Especially, if a primary genital HSV-2-infection of a
      pregnant woman is suspected, which can be proven by serological means only
      several weeks after infection, systemic therapy of the mother with aciclovir
      should be considered since materno-fetal transmission may occur due to the risk
      of maternal viraemia.

PMID- 11305195
TI  - [Melanotic neuroectodermal tumor of infancy].
AB  - BACKGROUND: The melanotic neuroectodermal tumor of infancy is a rare and so far
      as being classified neoplasm with a high rate of recurrence for one year after
      diagnosis. Since Krompecher described 1918 the tumor at first, only about 200
      cases are reported until today, mostly with manifestation in the maxillary
      region. CASE-REPORTS: The authors present two infants at the age of six and eight
      weeks with first clinical manifestation of the tumor in the maxillary region.
      Although there were no other common signs, the tumor destroyed wide areas of the
      mid-face. In spite of a treatment with radical surgery, recurrences occur rapidly
      in the first living year. CONCLUSIONS: Our clinical and histological findings
      show characteristics of local malignant growth. For these facts the radical
      resections of the primary tumor and its recurrences are individually the
      therapeutical consequences. A follow up of seven years of one infant shows a
      hypoplasm of the mid-face as a result of the inhibition of further growth by the
      loss of germs after maxillary hemisection.

PMID- 11305196
TI  - [Cutaneous lesions and blood count changes in a 9-month old girl with glutaric
      aciduria type I].
AB  - Non-specific cutaneous lesions are common in patients suffering from acute
      myeloid leukemia (AML). Leukemic skin infiltrates are present in about 30% of
      cases of monoblastic or myelomonocytic leukemia. The appearance of specific skin
      lesions can precede bone marrow involvement. We report the case of a 9-month-old
      girl with acute myelogenous leukemia (FAB M5) and glutaric aciduria type I which
      initially presented with cutaneous lesions, anemia and leukopenia.

PMID- 11305197
TI  - [Fatal outcome during physiotherapy (Vojta's method) in a 3-month old infant.
      Case report and comments on manual therapy in children].
AB  - Detailed clinical and neuropathological report on a fatal incident during the
      first manual therapy according to Vojta conducted in a 3 months old baby: during
      forced active rotation and head retraction the baby suffered from a bleeding into
      the adventitia of both her vertebral arteries at the level of C1 prompting
      ischemia of the caudal brainstem with subarachnoid haemorrhage around. It has to
      be suggested that similar cases already have occurred but have not been reported
      yet. There might be a time lag between the performance of physiotherapy and the
      beginning of neurologic symptoms. The risks of manual therapy in children will be
      discussed.

PMID- 11305198
TI  - [Familial Mediterranean fever].
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is characterized by febrile
      attacks, acute abdominal pain, pleuritis or arthritis and predominantly observed
      in ethnic groups of the Mediterranean area (Sephardic Jews, Turks, Armenians).
      Its most ominous manifestation is amyloidosis potentially leading to chronic
      renal failure. FMF is an inherited disorder caused by mutations of the FMF-gene,
      which first was described in 1997. CASE REPORT: We report a 10-year old turkish
      boy and his family presenting with an increased blood sedimentation rate (WBC)
      and recurrent attacks of acute abdominal pain. A molecular analysis was carried
      out, confirming a typical mutation of the FMF-gene. The patient remained free of
      symptoms after starting therapy with colchicine. CONCLUSION: Investigation of the
      FMF gene enables an early diagnosis in case of clinical suspect findings,
      subsequent colchicine administration may prevent amyloidosis.

PMID- 11305199
TI  - [The iodine supply of newborns. Comparison of iodine absorption and iodine
      excretion of mother and child].
AB  - BACKGROUND: Since 1989 the use of iodized salt has been allowed in Germany,
      additional supplementation with iodide tablets has been recommended during
      pregnancy and lactation. This study was undertaken to clarify whether the iodine
      intake of neonates and young infants improved since then. PATIENTS AND METHODS:
      In the first part of the study the urinary iodine excretion of 52 newborns and
      their mothers in 1998 was compared to data of similar studies 1983 in the area of
      Gottingen and 1982 in the areas of Heidelberg and Rothenburg, Germany. All these
      are geographically low-iodine areas. In the second part the iodine supply of
      infants in 1998-1999 under feeding with mother's milk or formulas in 1998 and
      1999 was obtained by measuring iodide concentrations in urine and milk using a
      high pressure liquid chromatography (HPLC) method. RESULTS: 45% of pregnant women
      were without iodide supplementation in 1998. In 1998 the median urinary iodide
      concentration during the first week of life was 4.3 micrograms/dl, which was more
      than twice that found in 1983 (1.75 micrograms/dl). Infants feeding by mother's
      milk without maternal iodine supplementation or by semi-elementary diet had the
      lowest urinary iodine excretion, whereas significantly higher values were
      measured when feeding formulas for term or preterm infants. CONCLUSIONS: The
      iodine intake of newborns has markedly improved during 15 years. The WHO
      criterias for adequate iodine supply (TSH < 5 microU/ml and urinary iodine >/ =
      10 micrograms/dl) were only partly fulfilled in Gottingen indicating that a mild
      iodine deficiency still exists with the risk of iodine deficiency disorders.

PMID- 11305200
TI  - [Paget-von Schroetter syndrome as an occupational accident].
AB  - HISTORY AND CLINICAL FINDINGS: Two men and one woman developed typical symptoms
      of a thrombosis in the arms after unusual physical effort at their work place (a
      coal miner after a bad fall, a radiographer after having to catch a patient, a
      painter after jerkily moving a heavy piece of furniture). INVESTIGATIONS AND
      DIAGNOSIS: In all three patients a thrombosis of the subclavian vein was
      demonstrated by duplex scans or phlebography. In two patients tests for
      hypercoagulability were unremarkable. None of the patients had a thoracic outlet
      syndrome. TREATMENT AND COURSE: After initial local thrombolytic or heparin
      therapy alone, phenprocoumon treatment over several months was given in two
      cases, and in one case low-molecular-weight heparin was administered over several
      months. All three patients complained of strain-related residual symptoms in the
      affected arm (pain, swelling, easy fatigability). In all three cases, the
      accident insurer recognized the incident to be a work-related accident.
      CONCLUSION: Patients with a Paget-Schroetter syndrome resulting from a sudden and
      unusual physical effort at work, which is covered by statutory accident
      insurance, must be reported to the accident insurer as a work-related accident in
      order to safeguard individual medical claims of the patient and for general
      medical and epidemiological reasons.

PMID- 11305201
TI  - [Rare complication of a heparin-induced thrombocytopenia type II].
AB  - HISTORY AND CLINICAL FINDINGS: A 63-year-old man was admitted to a surgery
      department with fracture of the acetabulum and luxation of the hip joint. Eight
      days after intracondylar nail-extension during subcutaneous heparin prophylaxis
      he developed a dramatic deterioration of his condition with severe abdominal pain
      and fever and was admitted to our hospital. INVESTIGATIONS: White cell count was
      12,000/microliter, C-reactive protein 7.90 mg/dl. CT-scan, abdominal ultrasound,
      mesenteric angiography and exploratory laparotomy revealed no pathological
      findings. At day 13 abdominal ultrasound showed adrenal haemorrhages on the
      right. Together with a drop in platelet count below 50,000/microliter, adrenal
      haemorrhage caused by heparin-induced thrombocytopenia (type II; immunological
      [HIT II]) was suggested. THERAPY: After discontinuation of heparin and starting
      therapy with recombinant hirudin and hydrocortisone, a dramatic clinical recovery
      followed within 24 hours. One year after the initial diagnosis the patient is in
      a good condition. CONCLUSION: When abdominal pain, hypotension and fever occurs
      with a drop in platelet count during heparin therapy HIT II should be considered.
      An early diagnosis is essential for treatment of this life-threatening
      complication at an early stage.

PMID- 11305202
TI  - [Long-term medical treatment of pulmonary hypertension].

PMID- 11305203
TI  - [Does mistletoe therapy influence the defense against epithelial tumors? A
      critical immunologic analysis].

PMID- 11305204
TI  - [Guidelines for "coagulation self-management"].

PMID- 11305205
TI  - [Are internists blind to the surgical viewpoint?].

PMID- 11305206
TI  - [Significance of alkaline phosphatase isoenzymes in bone].

PMID- 11305207
TI  - [Elevated hormone levels without endocrinopathy: hypercortisoluria and
      hypoglycemia as facticious disorders].
AB  - A 29-year-old female patient with weight gain and intermittent hypertension was
      suspected of having Cushing's syndrome due to conspicuous hypercortisoluria.
      Specific laboratory tests demonstrated that the urine samples contained
      prednisolone, which had resulted in a false positive elevation of urine-free
      cortisol measurements. The patient admitted to having taken prednisolone tablets
      and also to having added them to several urine collections. In a 21-year-old male
      patient with unexplained hypoglycaemia, hypoglycaemia was recorded during a 72
      hour fast together with an elevated level of plasma insulin and a low level of
      plasma C-peptide. The presence of insulin autoantibodies could be excluded,
      making a diagnosis of factitious hypoglycaemia highly likely. Both patients were
      confronted with the factitious disorder and received psychiatric counselling,
      after which no further problems arose. Where excessive hormone levels occur, the
      possibility of a factitious disorder needs to be considered. In such cases,
      specific supplementary laboratory tests may prove helpful.

PMID- 11305208
TI  - [Penicillin for acute throat infections. Are there arguments for modifying the
      guidelines of the Dutch College of General Practitioners?].
AB  - A recent study concludes that a 7-day penicillin treatment for a sore throat is
      superior to a 3-day treatment or a placebo, because the symptoms are resolved two
      days earlier. Prior to this study, the difference--based on the conclusions of a
      Cochrane review--was thought to be just 8 hours. The total number of patients
      included was too small to conclude that penicillin could reduce the number of
      short-term and long-term complications. In the guidelines of the Dutch College of
      General Practitioners, a 7-day penicillin treatment for a sore throat is only
      recommended in severe cases. It is still quite acceptable for Dutch GPs to
      discuss the treatment options for a sore throat with their patients. A change to
      the current guidelines is not necessary.

PMID- 11305209
TI  - [Activated protein C, coagulation, inflammation, and treatment of severe sepsis].
AB  - During the past 20 years several treatments designed to reduce inflammatory
      responses to sepsis have been unsuccessful. Sepsis results from a generalised
      inflammatory and procoagulant response to an infection. Activated protein C, a
      component of the anticoagulant system, is an anti-thrombotic serine protease with
      anti-inflammatory properties. A recently published study reported the results of
      a large clinical trial in which recombinant human activated protein C
      significantly reduced mortality in patients with severe sepsis. Treatment with
      activated protein C also reduced circulating D-dimer and IL-6 levels, which are
      markers of coagulation activation and inflammation. There are several reasons why
      activated protein C could be effective in sepsis. Firstly, reduced levels of
      protein C are found during sepsis and are associated with an increased risk of
      death. Secondly, activated protein C can directly inhibit factors Va and VIIIa,
      resulting in decreased thrombin formation. Finally, activated protein C can
      reduce plasminogen activator inhibitor I, thereby stimulating fibrinolysis. In
      addition to these effects on thrombin formation, activated protein C directly
      reduces pro-inflammatory responses by as yet unknown mechanisms.

PMID- 11305210
TI  - [Emergent viral infections].
AB  - The emergence and re-emergence of viral infections is an ongoing process. Large
      scale vaccination programmes led to the eradication or control of some viral
      infections in the last century, but new viruses are always emerging. Increased
      travel is leading to a rise in the importation of exotic infections such as
      dengue and hepatitis E, but also of hepatitis A, which is no longer endemic.
      Apart from import diseases new viruses have appeared (Nipah-virus and transfusion
      transmitted virus). Existing viruses may suddenly cause more severe diseases,
      e.g. infection by enterovirus 71. The distribution area of a virus may change,
      e.g. in case of West Nile virus, an Egyptian encephalitis virus that appears to
      have established itself in the USA. Furthermore, there is no such thing as a
      completely new virus; it is always an existing virus that has adapted itself to
      another host or that was already present in humans but has only recently been
      discovered. A number of factors facilitate the emergence of new infectious
      diseases. These include intensive animal husbandry and the transport of animals.
      The unexpected appearance of West Nile virus in the western hemisphere was
      possibly due to animal transportation.

PMID- 11305211
TI  - [Hemolytic uremic syndrome in children].
AB  - In Europe, haemolytic uraemic syndrome (HUS) is the most frequent cause of acute
      renal insufficiency during childhood. In the Netherlands about 20 children per
      year are seriously affected. Following a prodromal phase of mostly bloody
      diarrhoea, the main symptoms become evident, namely, haemolytic anaemia,
      thrombocytopenia and renal failure. The syndrome is caused by a verocytotoxin
      producing Escherichia coli, which damages the endothelium of the arterioles and
      glomeruli in the kidney. In humans, the most important cause of infection is the
      consumption of infected food-stuffs. After transport through the intestinal
      epithelium, the toxin becomes attached to the neutrophils, which transport it
      through the circulatory system, mainly to the kidneys where it has a toxic
      effect. Why the endothelial cells in these organs are the main targets for this
      toxin is as yet unknown. A symptomatic treatment is given to the 10% of infected
      patients who develop HUS. Increasing knowledge about the pathogenesis has
      resulted in new forms of treatment that will be studied during the next few
      years.

PMID- 11305212
TI  - [Clinical thinking and decision making in practice. A child with tachypnea and
      dyspnea].
AB  - A 6-year-old girl had been ill for a number of weeks, had fever for 5 days and
      complained of pain below the left costal arch and in the left shoulder, linked to
      the breathing. An unexplained tachypnoea was also present. The leukocyte
      differentiation showed 90% blasts; a bone marrow puncture then led to the
      diagnosis of acute non-lymphatic leukaemia, and hyperhydration and alkalinization
      were started. The patient died unexpectedly after a few days from massive
      leukostasis in pulmonary arteries. If vital functions are impaired, it should
      always be attempted to find an explanation, for which an underlying disease may
      serve as a guideline.

PMID- 11305213
TI  - [Diagnostic image (31). Urethral prolapse].
AB  - In an 8-year old negroid girl vaginal bleeding was caused by urethral prolapse.

PMID- 11305214
TI  - [Juvenile xanthogranuloma: a form of histiocytosis with an excellent prognosis].
AB  - In three patients, a girl aged six weeks and two boys aged eight and three
      months, juvenile xanthogranuloma was diagnosed. This is a rare cutaneous disorder
      that predominantly occurs during infancy and early childhood. It is one of the
      non-malignant, non-Langerhans cell histiocytoses (class II histiocytoses). It is
      characterized by a circumscript, firm, yellow-brown and sometimes pink-red nodule
      or papule located mainly on the face or scalp. Diagnosis can be made on the
      clinical appearance. However, this may need to be confirmed by a
      histopathological investigation, which includes immunohistochemical stains. In
      contrast to generalized histiocytoses, the prognosis of juvenile xanthogranuloma
      is excellent: the cutaneous tumour disappears spontaneously in one to six years.
      However, extracutaneous involvement, which is most frequently located in the eye,
      can occur. Moreover, juvenile xanthogranuloma is associated with
      neurofibromatosis type I and juvenile chronic myeloid leukaemia. This rare but
      possibly life-threatening systemic involvement justifies meticulous follow-up.

PMID- 11305215
TI  - [Hemicraniectomy for treatment of malignant medial cerebral artery infarction in
      3 patients].
AB  - In three patients, a 52-year old man, a 54-year old man and a 17-year old woman,
      sudden neurological signs such as hemiparalysis and hemihypaesthesia developed,
      with diminished consciousness occurring at a later stage. Imaging revealed total
      infarction of the area supplied by the right middle cerebral artery with the
      threat of intracranial hypertension. Once informed consent had been obtained from
      the patient's representatives, hemicraniectomy with dural augmentation was
      performed. Although the primary neurological deficit persisted, the three
      patients assessed their quality of life as valuable with their Barthel scores
      ranging from 45 to 90. Total infarction of the middle cerebral artery may result
      in intracranial hypertension and transtentorial herniation owing to the
      development of cytotoxic oedema, particularly in young patients. The prognosis of
      this condition is poor partly due to the limited effect of non-surgical
      treatment. Hemicraniectomy with dural augmentation prevents secondary brain
      damage caused by the space-occupying effect of the infarct. This operation
      reduces mortality considerably. The findings in these patients along with the
      results in the literature warrant a randomised study of the results of
      hemicraniectomy in patients with malignant middle cerebral artery infarction.

PMID- 11305217
TI  - [Definition of 'quackery' in the public debate on alternative therapies].

PMID- 11305216
TI  - [Enterobacter cloacae epidemic on a neonatal intensive care unit due to the use
      of contaminated thermometers].
AB  - From December 1999 to March 2000 a nosocomial outbreak of multiresistant
      Enterobacter cloacae occurred in the neonatal intensive care unit (NICU) at the
      VU Medical Center, Amsterdam, the Netherlands. Twenty-six patients were infected
      or colonized with this strain resistant to third generation cephalosporins and
      with decreased sensitivity for aminoglycosides. Three neonates experienced sepsis
      with E. cloacae with serious clinical symptoms and two of them died. Comparison
      of the Enterobacter isolates by amplified-fragment length polymorphism indicated
      that this outbreak was caused by the spread of a single strain. Infection control
      precautions were initiated in order to stop further spread; barrier precautions,
      enforcement of hand disinfection and cohorting of colonized patients. A
      multidisciplinary crisis team coordinated these infection control precautions and
      informed all persons involved. Analysis of antibiotic usage in 1999 showed an
      increase in the use of third generation cephalosporins from November onwards. Due
      to the resistance pattern of the epidemic strain the use of third generation
      cephalosporins was discontinued in February 2000. At the end of February the NICU
      was temporarily closed. The epidemic strain of E. cloacae was isolated from one
      digital rectal thermometer. Patient use of thermometers and disposable coverings
      for rectal thermometers were introduced to eliminate this possible means of
      spread. No spread of multiresistant E. cloacae was found following the
      introduction of these interventions. Once all the neonates had been transferred,
      the NICU was disinfected and reopened in March.

PMID- 11305218
TI  - [Definition of 'quackery' in the public debate on alternative therapies].

PMID- 11305219
TI  - [From gene to disease; tumor necrosis factor receptor and familial periodic fever
      syndrome].

PMID- 11305220
TI  - Inter- and intrajudge reliability for videofluoroscopic swallowing evaluation
      measures.
AB  - Interjudge reliability for videofluoroscopic (VFS) swallowing evaluations has
      been investigated, and results have, for the most part, indicated that
      reliability is poor. While previous studies are well-designed investigations of
      interjudge reliability, few reports of intrajudge reliability are available for
      VFS measures derived from frame-by-frame analysis that clinicians typically
      employ. The purpose of this study was to examine the inter- and intrajudge
      reliability of VFS examination measures commonly used to assess swallowing
      functions. No training to criteria occurred. VFS examinations were conducted on
      20 patients who had suffered a stroke within six weeks and had no structural
      abnormalities or tracheostomies. Three clinical judges served as subjects and
      rated the VFS examinations from videotape using frame-by-frame analysis. A
      clinician's repeated review of measures employed in the 20 examinations indicated
      high intrajudge reliability for a number of measures, suggesting that an
      experienced clinician may employ consistent standards for rating certain VFS
      measures across patients and time. These standards appear to vary among
      clinicians and yield unacceptable interjudge reliability. The need to train
      clinicians to criteria to improve interjudge reliability is discussed.

PMID- 11305221
TI  - Effect of liquid bolus consistency and delivery method on aspiration and
      pharyngeal retention in dysphagia patients.
AB  - There is no empirically derived consensus as to what food consistency types and
      method of food delivery (spoon, cup, straw) should be included in the
      videofluoroscopic swallowing (VFSS) studies. In the present study, we examine the
      rates of aspiration and pharyngeal retention in 190 dysphagic patients given thin
      (apple juice) and thick (apricot nectar) liquids delivered by teaspoon and cup
      and ultrathick (pudding-like) liquid delivered by teaspoon. Each patient was
      tested with each of the bolus/delivery method combinations. The fractions of
      patients exhibiting aspiration for each bolus/method of delivery combination were
      (1) thick liquids (cup), 13.2%; (2) thick liquids (spoon), 8.9%; (3) thin liquids
      (cup), 23.7%; (4) thin liquids (spoon), 15.8%, (5) ultrathick liquids (spoon),
      5.8%. In each comparison [thick liquid (cup) vs. thick liquid (spoon), thin
      liquid (cup) vs. thin liquid (spoon), thick liquid (cup) vs. thin liquid (cup),
      thick liquid (spoon) vs. thin liquid (spoon), and thick liquid (spoon) vs.
      ultrathick liquid (spoon)], the p value for chi 2 was < 0.001. These results
      suggest that utilizing thin, thick, and ultrathick liquids and delivery by cup
      and spoon during a VFSS of a patient with mild or moderate dysphagia can increase
      the chances of identifying a consistency that the patient can swallow without
      aspirating and without pharyngeal retention after swallowing.

PMID- 11305222
TI  - The effect of compliance on clinical outcomes for patients with dysphagia on
      videofluoroscopy.
AB  - This study investigates clinical outcomes and the degree of compliance in
      patients who received advice on dysphagia management and the effect of the level
      of compliance on the incidence of chest infections and aspiration pneumonia,
      cause of death, and hospital readmission. We performed a retrospective cohort
      study of 140 patients who had videofluoroscopic studies at Princess Margaret
      Hospital, Christchurch, New Zealand, from 1 January 1996 to 30 June 1997. The
      degree to which recommendations on dysphagia management were followed was
      correlated with the incidence of chest infections, aspiration pneumonia, and
      readmissions to the hospital. Cause of death, including the contribution of
      aspiration pneumonia, was assessed by review of medical records and death
      certificates. Information was available for 89% of the cohort. Twenty-one percent
      of the survivors never complied with the advice given. Noncompliant subjects were
      younger (p < 0.05) and more likely to be living at home rather than receiving
      institutional care (p = 0.05). Noncompliers had more hospital admissions because
      of chest infections or aspiration pneumonia (22% vs. 1.5%; p < 0.001). Home
      dwelling noncompliant subjects received more courses of antibiotics (p < 0.02),
      but there was no difference in the number of chest infections. Fifty-four people
      died during the study period. Aspiration pneumonia was recorded as a definite or
      probable cause of death in 26 (52%) of the 50 subjects for whom reliable
      information was available and in 6 of 7 subjects who made a deliberate and
      documented decision not to comply. We conclude that noncompliance with
      recommendations about dysphagia management is associated with adverse outcomes.
      There was a high mortality rate and aspiration pneumonia was a common cause of
      death.

PMID- 11305223
TI  - Effects of age, gender, bolus volume, and trial on swallowing apnea duration and
      swallow/respiratory phase relationships of normal adults.
AB  - The effects of age, gender, bolus volume, and trial on swallowing apnea duration
      (SAD) and swallow/respiratory phase relationships were examined. Sixty adults,
      composed of ten males and ten females in each of three age groups (i.e., 20-39,
      40-59, and 60-83 years), participated. SAD was assessed via nasal airflow during
      saliva swallows and 10-, 15-, 20-, 25-mL bolus volumes across three trials.
      Results revealed SAD is consistent across trial (p > 0.05). Significant main
      effects of age, gender, and bolus volume were found (p < 0.05), i.e., elderly
      adults had longer SAD than young and middle-aged adults; women had longer SAD
      than men; and SAD increased as bolus volume increased. With respect to saliva
      swallows, a significant interaction of age by gender was found (p < 0.05), i.e.,
      males exhibited a decrease in SAD with increasing age while females exhibited an
      increase in SAD with increasing age. Concerning swallow/respiratory phase
      relationships, the pattern of exhale-swallow-exhale was evident during 62% of
      participants' swallows. Furthermore, age, gender, or bolus volume did not predict
      the pattern of exhale-swallow-exhale (p > 0.05).

PMID- 11305224
TI  - Dysphagia in a patient with Wegener's granulomatosis: case report.
AB  - Wegener's Granulomatosis is an autoimmune disease characterized by a rare form of
      systemic vasculitis which can result in damage to vital organs of the body by
      restricting blood flow to those organs. It affects various systems of the body
      including the central nervous system and cranial nerves. To our knowledge, there
      are no previous described cases of oropharyngeal dysphagia in these patients.
      This paper describes and discusses a case of oropharyngeal dysphagia in a patient
      with Wegener's Granulomatosis.

PMID- 11305225
TI  - Effect of tracheotomy tube occlusion on upper esophageal sphincter and pharyngeal
      pressures in aspirating and nonaspirating patients.
AB  - The biomechanics of the pharyngeal swallow in patients with a tracheotomy tube
      were investigated with manometry. Upper esophageal sphincter (UES) and pharyngeal
      pressure recordings were made with and without occlusion of the tracheotomy tube.
      Criteria for selection were ability to tolerate tracheotomy tube occlusion for
      both 5 minutes prior to and during the first manometric analysis, absence of
      surgery to the upper aerodigestive tract other than tracheotomy, and no history
      of oropharyngeal cancer or stroke. Aspiration was determined objectively by
      fiberoptic endoscopic evaluation of swallowing (FEES) immediately prior to
      manometric recording. Eleven adult individuals with tracheotomy participated; 7
      swallowed successfully and 4 exhibited aspiration on FEES. The results indicated
      no significant effect of tracheotomy tube occlusion on UES or pharngeal pressures
      in either aspirating or nonaspirating patients. It was concluded that the
      biomechanics of the swallow as determined by UES and pharyngeal manometric
      pressure measurements were not changed significantly by tracheotomy tube
      occlusion in aspirating or nonaspirating patients. These results support previous
      observations that subjects either aspirated or swallowed successfully regardless
      of tracheotomy tube occlusion status.

PMID- 11305226
TI  - Feeding skills and growth after one year of intraoral appliance therapy in
      moderately dysphagic children with cerebral palsy.
AB  - We determined changes in functional feeding skills and growth after one year of
      intraoral appliance therapy in dysphagic children. Twenty children, 4.2-13.1
      years of age (average 8.3 +/- 0.9 years), participated in this study. Children
      wore the appliance daily. Phase I of treatment (6 months) aimed primarily at
      stabilizing the mandible and phase II aimed at facilitating ingestive skills. A
      control period of 6 months preceded treatment. Functional feeding skills improved
      significantly during phase I beyond changes seen during the control period.
      Further significant improvement occurred in chewing during phase II. All children
      significantly gained weight (kg) during the control period, as well as during the
      two treatment phases. This weight gain was sufficient for children to maintain
      their growth trajectory. There was also significant growth in height (cm). This
      growth spurt was characterized by marginal catch-up. Jaw stabilization was a
      major contributor to the significant improvement in functional feeding skills.
      Weight gain cannot be attributed to intervention because it occurred during the
      control period and was the same in magnitude through both treatment phases.
      However, it permitted a period of growth in stature which previously had been
      described only after tube feeding.

PMID- 11305227
TI  - Computer measurement of oral movement in swallowing.
AB  - This article describes a computer program that automatically detects and tracks
      small metal markers affixed to a subject's tongue and teeth in fluoroscopic image
      sequences of swallowing. The program, written in Microsoft Visual C++ using
      Windows NT 4.0 and the SAVANT imaging toolkit, involves marker detection and
      marker tracking. Marker detection is done by template matching. A generic marker
      template was designed by extracting the grayvalues of pixels within an imaged
      marker. Template matching with a weighted center-of-mass calculation determined
      marker location with subpixel accuracy. Marker tracking employed a nearest
      neighbor algorithm since (a) the movement of each marker was less than the
      distance between any two markers and (b) marker trajectories did not overlap.
      Effects of head motion were attenuated by computing tongue trajectories with
      respect to a constant frame of reference given by reference markers on the
      maxillary teeth. Motions were converted from pixels/frame to millimeters/second
      using a calibration ring secured to the subject's neck. Results for several image
      sequences showed that our program performs very well in terms of marker detection
      and trajectory determination. Comparison of automatic and manual tracking of the
      same image sequences indicated a high degree of correspondence. Automatic
      tracking of oral movement by computer is a useful tool in kinematic studies of
      swallowing.

PMID- 11305228
TI  - The magnocellular theory of developmental dyslexia.
AB  - Low literacy is termed 'developmental dyslexia' when reading is significantly
      behind that expected from the intelligence quotient (IQ) in the presence of other
      symptoms--incoordination, left-right confusions, poor sequencing--that
      characterize it as a neurological syndrome. 5-10% of children, particularly boys,
      are found to be dyslexic. Reading requires the acquisition of good orthographic
      skills for recognising the visual form of words which allows one to access their
      meaning directly. It also requires the development of good phonological skills
      for sounding out unfamiliar words using knowledge of letter sound conversion
      rules. In the dyslexic brain, temporoparietal language areas on the two sides are
      symmetrical without the normal left-sided advantage. Also brain 'warts'
      (ectopias) are found, particularly clustered round the left temporoparietal
      language areas. The visual magnocellular system is responsible for timing visual
      events when reading. It therefore signals any visual motion that occurs if
      unintended movements lead to images moving off the fovea ('retinal slip'). These
      signals are then used to bring the eyes back on target. Thus, sensitivity to
      visual motion seems to help determine how well orthographic skill can develop in
      both good and bad readers. In dyslexics, the development of the visual
      magnocellular system is impaired: development of the magnocellular layers of the
      dyslexic lateral geniculate nucleus (LGN) is abnormal; their motion sensitivity
      is reduced; many dyslexics show unsteady binocular fixation; hence poor visual
      localization, particularly on the left side (left neglect). Dyslexics' binocular
      instability and visual perceptual instability, therefore, can cause the letters
      they are trying to read to appear to move around and cross over each other.
      Hence, blanking one eye (monocular occlusion) can improve reading. Thus, good
      magnocellular function is essential for high motion sensitivity and stable
      binocular fixation, hence proper development of orthographic skills. Many
      dyslexics also have auditory/phonological problems. Distinguishing letter sounds
      depends on picking up the changes in sound frequency and amplitude that
      characterize them. Thus, high frequency (FM) and amplitude modulation (AM)
      sensitivity helps the development of good phonological skill, and low sensitivity
      impedes the acquisition of these skills. Thus dyslexics' sensitivity to FM and AM
      is significantly lower than that of good readers and this explains their problems
      with phonology. The cerebellum is the head ganglion of magnocellular systems; it
      contributes to binocular fixation and to inner speech for sounding out words, and
      it is clearly defective in dyslexics. Thus, there is evidence that most reading
      problems have a fundamental sensorimotor cause. But why do magnocellular systems
      fail to develop properly? There is a clear genetic basis for impaired development
      of magnocells throughout the brain. The best understood linkage is to the region
      of the Major Histocompatibility Complex (MHC) Class 1 on the short arm of
      chromosome 6 which helps to control the production of antibodies. The development
      of magnocells may be impaired by autoantibodies affecting the developing brain.
      Magnocells also need high amounts of polyunsaturated fatty acids to preserve the
      membrane flexibility that permits the rapid conformational changes of channel
      proteins which underlie their transient sensitivity. But the genes that underlie
      magnocellular weakness would not be so common unless there were compensating
      advantages to dyslexia. In developmental dyslexics there may be heightened
      development of parvocellular systems that underlie their holistic, artistic,
      'seeing the whole picture' and entrepreneurial talents.

PMID- 11305229
TI  - Egocentric mental rotation in Hungarian dyslexic children.
AB  - A mental rotation task was given to 27 dyslexic children (mean age 9 years, 2
      months) and to 28 non-dyslexic children (mean age 8 years, 8 months). Pictures of
      right and left hands were shown at angles of 0, 50, 90 and 180 degrees, and the
      subjects were required to indicate whether what was shown was a right hand or a
      left hand. It was found that, in this task, the dyslexics did not show the normal
      pattern of response times at different angles, and also, that they made more
      errors than the controls. It is argued that this result is compatible with
      hypothesis that, in typical cases of dyslexia, there is a malfunctioning in the
      posterior parietal area.

PMID- 11305230
TI  - From language to reading and dyslexia.
AB  - This paper reviews evidence in support of the phonological deficit hypothesis of
      dyslexia. Findings from two experimental studies suggest that the phonological
      deficits of dyslexic children and adults cannot be explained in terms of
      impairments in low-level auditory mechanisms, but reflect higher-level language
      weaknesses. A study of individual differences in the pattern of reading skills in
      dyslexic children rejects the notion of 'sub-types'. Instead, the findings
      suggest that the variation seen in reading processes can be accounted for by
      differences in the severity of individual children's phonological deficits,
      modified by compensatory factors including visual memory, perceptual speed and
      print exposure. Children at genetic risk who go on to be dyslexic come to the
      task of reading with poorly specified phonological representations in the context
      of a more general delay in oral language development. Their prognosis (and that
      of their unaffected siblings) depends upon the balance of strengths and
      difficulties they show, with better language skills being a protective factor.
      Taken together, these findings suggest that current challenges to the
      phonological deficit theory can be met.

PMID- 11305231
TI  - Critical response to dyslexia, literacy and psychological assessment. (report by
      a working party of the division of educational and child psychology of the
      British psychological society). A view from the chalk face.

PMID- 11305232
TI  - [Multidisciplinary therapy of colorectal cancer].
AB  - A multidisciplinary program for the treatment of colorectal cancer is described.
      The main objective of the authors has been to define uniform up to date
      guidelines based on recent progress in the treatment of colorectal cancer.
      Preoperative diagnostic procedures are summarized which advance determination of
      clinical stage and prognosis. These information essentially determine care.
      Sequences of surgical methods, preoperative and postoperative radiotherapy and
      medical treatments are discussed according to tumor stages. Guidelines for
      surveillance following active treatment and recommendation for the screening of
      population at high risk for colorectal cancer are presented.

PMID- 11305233
TI  - [Respiratory syncytial virus infection in high-risk infants].
AB  - The authors describes the frequency of respiratory syncytial virus (RSV)
      infections in high risk infants in ten hospitals, between 01.02.1999.-15.03.1999.
      RSV antigen test were performed from the nasopharyngeal or throat swabs of 58
      infants with respiratory tract infections. Thirteen patients were positive. Among
      them 11 were prematures. Six infants were still receiving treatment in Neonatal
      Intensive Care Unit, while seven infants were readmitted to a Pediatric Intensive
      Care Unit. Distribution of risk factors (prematurity, bronchopulmonary dysplasia,
      ventilation in newborn period, smoking in the family, unseparated brothers or
      sisters) in patients were comparable with the data of literature. Eight infants
      needed head box O2-therapy. No deaths were detected. The results of this
      preliminary study in Hungary might emphasize the importance of RSV infection, as
      a frequent cause of rehospitalization and the possibility of prevention
      (immunoglobulin, palivizumab).

PMID- 11305234
TI  - [Treatment of renal artery stenoses with stent implantation].
AB  - The authors report on their experience with the treatment of renovascular
      hypertension by stent implantation. In the past 4 years different types of stents
      (Palmaz [9], Palmaz-Corinthian [4], Memotherm [1] and AVE [1]) were implanted
      into 15 renal arteries of 11 patients. The indication was primary in 8 cases, and
      secondary in 3 patients, because of restenosis of a previously dilated renal
      artery. 14 stents were implanted into narrowed renal arteries, and in the
      remaining one case a stent was placed in an occluded renal artery immediately
      after recanalization. The technical success was 100%. In all but the recanalized
      case in which the renal artery was occluded, stents are still open. On the basis
      of this experience and the literature, the authors suggest the more extensive
      usage of this less invasive method.

PMID- 11305235
TI  - [Virtual bronchoscopy: a new non-invasive diagnostic method in pulmonology].
AB  - Virtual reality (3 dimensional modelling of the human body) has developed as a
      convergence of advancing digital imaging modalities and computer graphics
      technologies. With this method endoscopic simulations of cavitary organs are
      feasible. Virtual bronchoscopy was initially described in 1993. The authors
      selected patient with previously detected stenosis of the trachea or the main
      bronchi with bronchofiberscope. They performed targeted, thin-slice helical
      computer tomography of the lesions. These data were transferred to a workstation
      and the virtual endoscopic models of the airways were generated using dedicated
      software. Based on cases the authors describe their preliminary experience with
      the method. The findings were compared with those of bronchofiberscopy. Analyzing
      these results and the literature the potential clinical applications of virtual
      bronchoscopy are discussed.

PMID- 11305236
TI  - [From carbonic water bathing to cardiac rehabilitation center. The history of the
      State Heart Hospital in Balatonfured].

PMID- 11305237
TI  - 2000-2001 legislative and regulatory update.

PMID- 11305238
TI  - Proline in alpha-helical kink is required for folding kinetics but not for kinked
      structure, function, or stability of heat shock transcription factor.
AB  - The DNA-binding domain of the yeast heat shock transcription factor (HSF)
      contains a strictly conserved proline that is at the center of a kink. To define
      the role of this conserved proline-centered kink, we replaced the proline with a
      number of other residues. These substitutions did not diminish the ability of the
      full-length protein to support growth of yeast or to activate transcription,
      suggesting that the proline at the center of the kink is not conserved for
      function. The stability of the isolated mutant DNA-binding domains was unaltered
      from the wild-type, so the proline is not conserved to maintain the stability of
      the protein. The crystal structures of two of the mutant DNA-binding domains
      revealed that the helices in the mutant proteins were still kinked after
      substitution of the proline, suggesting that the proline does not cause the alpha
      helical kink. So why are prolines conserved in this and the majority of other
      kinked alpha-helices if not for structure, function, or stability? The mutant DNA
      binding domains are less soluble than wild-type when overexpressed. In addition,
      the folding kinetics, as measured by stopped-flow fluorescence, is faster for the
      mutant proteins. These two results support the premise that the presence of the
      proline is critical for the folding pathway of HSF's DNA-binding domain. The
      finding may also be more general and explain why kinked helices maintain their
      prolines.

PMID- 11305239
TI  - Prediction of a common beta-propeller catalytic domain for fructosyltransferases
      of different origin and substrate specificity.
AB  - The three-dimensional (3D) structure of fructan biosynthetic enzymes is still
      unknown. Here, we have explored folding similarities between reported microbial
      and plant enzymes that catalyze transfructosylation reactions. A sequence
      structure compatibility search using TOPITS, SDP, 3D-PSSM, and SAM-T98 programs
      identified a beta-propeller fold with scores above the confidence threshold that
      indicate a structurally conserved catalytic domain in fructosyltransferases
      (FTFs) of diverse origin and substrate specificity. The predicted fold appeared
      related to that of neuraminidase and sialidase, of glycoside hydrolase families
      33 and 34, respectively. The most reliable structural model was obtained using
      the crystal structure of neuraminidase (Protein Data Bank file: 5nn9) as
      template, and it is consistent with the location of previously identified
      functional residues of bacterial levansucrases (Batista et al., 1999; Song &
      Jacques, 1999). The sequence-sequence analysis presented here reinforces the
      recent inclusion of fungal and plant FTFs into glycoside hydrolase family 32, and
      suggests a modified sequence pattern H-x (2)-[PTV]-x (4)-[LIVMA]-[NSCAYG]-[DE]-P
      [NDSC][GA]3 for this family.

PMID- 11305240
TI  - [Professor Doctor Arthur de Carvalho Azevedo (01/03/1916 - 05/10/2000)].

PMID- 11305241
TI  - Health surveillance of Glasgow medical undergraduates pursuing elective studies
      abroad (1992-1998).
AB  - BACKGROUND: An integral part of the training for many UK medical undergraduates
      involves a period of elective study abroad. There is concern about the health
      risks this poses to the students, and uncertainty regarding the responsibility
      this places on medical schools. METHODS: Annually since 1992, medical
      undergraduates at Glasgow University have been asked to complete and return a
      confidential questionnaire on return from their elective studies. This records
      personal demographic details, the countries visited, and information about
      illnesses experienced. Analyses were conducted on the students' health
      experiences, lifestyle, the health precautions taken, and the climates
      experienced. RESULTS: Global statistics were compiled on 750 respondents. A
      subset of 267 completed a more extensive, post-1996, questionnaire enabling
      detailed study of comparative illness rates. A majority took pretravel health
      advice, visited only one country, stayed for 1 to 2 months, and experienced a
      tropical climate. Forty-five percent reported symptoms of illness, and alimentary
      symptoms predominated (77% of those ill). Higher illness rates were reported in
      those who experienced a hot desert or tropical climate compared with those who
      did not. There was correlation between taking professional pretravel health
      advice and exposure to a more hazardous climate. CONCLUSIONS: The attack rate for
      medical students on electives compares favorably to that for package
      holidaymakers; similarly the attack rate for students staying in the tropics
      compared with other travelers. A preexisting health problem did not predispose to
      a higher attack rate. Attack rates can be minimized by avoiding climatically
      extreme locations. This surveillance provides a focus of interest to the
      students, insight on minimizing avoidable health problems, evidences social
      responsibility by the Medical Faculty, and has the potential for expansion to
      other medical schools. Current Scottish medical school policies on HIV risk
      management would be strengthened by a more coordinated approach.

PMID- 11305242
TI  - Investigation on subclinical aspects related to intestinal parasitic infections
      among Thai laborers in Taipei.
AB  - BACKGROUND: The migration of foreign workers from developing regions to developed
      countries may potentially lead to transmission of intestinal parasitic
      infections. In order to determine the relationship between intestinal parasitic
      infections and the health status of foreign workers, 302 Thai laborers brought to
      Taiwan were examined in this study. Nine species of parasites were found in 64.9%
      of laborers; Opisthorchis viverrini, hookworm, Strongyloides stercoralis, Giardia
      lamblia, Trichuris trichiura, Fasciolopsis buski, Taenia sp, Echinostoma sp,
      Entamoeba coli. METHODS: From June 1992 to December 1993, a total of 302 Thai
      laborers, participating in the mandatory entry health examination at Chang-Gung
      Memorial Hospital, Lin-Kou Medical Center were interviewed and examined. These
      subjects underwent a physical examination, chest roentgenography, and serological
      tests for human immunodeficiency virus antibody, syphilis (VDRL), and hepatitis B
      surface antigen. RESULTS: Among the 302 Thai laborers examined, 196 (64.9%) were
      found to be infected with 1 to 5 species of parasites. All 193 infected Thai
      laborers were treated in Taiwan. Two or 3 courses of pyrantel pamoate,
      mebendazole, praziquantel, and metronidazole were administered to 119, 45, 24,
      and 5 infected patients respectively. After 1 week of treatment, all results of
      stool examinations were negative. CONCLUSION: Acquisition of infection has been
      determined to be related to the consumption of koipla, a dish prepared from
      uncooked freshwater fish. Not unexpectedly, in the present study, it was found
      that this species was the most important intestinal parasite among Thai laborers
      and was significantly associated with the consumption of koipla.

PMID- 11305243
TI  - Traveling with pets.

PMID- 11305244
TI  - A survey of the profile and perceived value of a London Travel Clinic.

PMID- 11305245
TI  - Inflammatory bowel disease in returning travelers.

PMID- 11305246
TI  - A case of probable imported Moniliformis moniliformis infection in Tasmania.

PMID- 11305247
TI  - Inappropriate use of mosquito bed nets in the prevention of malaria: lessons from
      a familial cluster of ovale malaria.

PMID- 11305248
TI  - Limitations of rapid tests for malaria diagnosis by travelers.

PMID- 11305249
TI  - Coriander spice oil: effects of fruit crushing and distillation time on yield and
      composition.
AB  - Crushing intensity and distillation time were evaluated for their effects on the
      oil yield and composition of steam-distilled essential oil from fruits of
      Coriandrum sativum var. microcarpum L. A comparison of oils produced by
      laboratory- and pilot-scale stills showed that the two still types gave
      comparable yields and oil composition. The laboratory still was then used to
      compare oil yields and compositions from fruits crushed at three different
      intensities, at intervals during a distillation period of 60 min. Both crushing
      intensity and distillation time had significant (P< 0.05) effects on the yield
      and composition of the oil. The maximum oil yield was less from the light-crushed
      fruits, but the rate of oil recovery was significantly P < 0.05) higher. From the
      light-crushed fruits, 95% of the maximum yield was extracted in 22.5 min compared
      with 32 and 39 min for the standard and heavy-crushed fruits, respectively. The
      effect of crushing intensity on oil composition was most pronounced on the low
      boiling-point a-pinene and on the higher-boiling-point geranyl acetate. Crushing
      had little effect on linalool content, but distillation time could be manipulated
      to alter the linalool content of the oil.

PMID- 11305250
TI  - In vitro inhibition studies of phytoene desaturase by bleaching ketomorpholine
      derivatives.
AB  - The herbicidal activities of homochiral steroisomeric 5-methy1-2-(3
      trifluoromethybenzyl)-3-keto- morpholine derivatives were investigated in vitro
      as inhibitors of phytoene desaturase, a key enzyme in carotenoid biosynthesis. It
      was demonstrated that ketomorpholines are classical bleaching compounds which
      directly inhibit phytoene desaturase, accumulating phytoene at the expense of
      colored carotenoids. Ketomorpholines interact with phytoene desaturase in a
      noncompetitive manner with respect to phytoene. A structure-activity
      investigation for in vitro inhibition of phtoene desaturase activity revealed
      that the relative and absolute stereochemistry is important for optimum
      inhibition for the 5-methyl derivatives, and that the distance of the phenyl
      group from the ketomorpholine ring is critical for the inhibitory potential. The
      average herbicidal score on 7 weeds and the in vitro I(50) values related very
      well with the exception of two compounds. It was postulated that the
      discrepancies may possibly occur through modification in plants to compounds that
      are either more or less active herbicides.

PMID- 11305251
TI  - Mosquitocidal, nematicidal, and antifungal compounds from Apium graveolens L.
      seeds.
AB  - The methanolic extract of Apium graveolens seeds was investigated for bioactive
      compounds and resulted in the isolation and characterization of mosquitocidal,
      nematicidal, and antifungal compounds sedanolide (1), senkyunolide-N (2), and
      senkyunolide-J (3). Their structures were determined by 1H and 13C NMR spectral
      methods. Compounds 1-3 gave 100% mortality at 25, 100, and 100 microg mL(-1),
      respectively, on the nematode, Panagrellus redivivus. Compound 1 showed 100%
      mortality at 50 microg mL(-1) on nematode, Caenorhabditis elegans, and fourth
      instar mosquito larvae, Aedes aegyptii. Also, it inhibited the growth of Candida
      albicans and Candida parapsilasis at 100 microg mL(-1). Compounds 2 and 3 were
      isolated for the first time from A. graveolens. This is the first report of the
      mosquitocidal, nematicidal, and antifungal activities of compounds 1-3.

PMID- 11305252
TI  - Ion chromatographic analysis of selected free amino acids and cations to
      investigate the change of nitrogen metabolism by herbicide stress in soybean
      (glycine max).
AB  - A simple and reliable method for the determination of NH4+, K+, Na+, aspartic
      acid, asparagine, glutamine, and alanine by ion chromatography has been
      developed. It is suitable for monitoring changes of nitrogen metabolism in
      soybean because it can accurately measure concentrations o asparagine and NH4+,
      two key substances for nitrogen storage and transport in this plant species
      Analysis of asparagine distribution in soybean indicated that higher levels (up
      to 18.4 micromol g(-1) of fresh mass) occur in stems and lower levels in roots
      (2.0 micromol g(-1) of fresh mass) and leaves (1.6 micromol g(-1) of fresh mass).
      When the herbicide metsulfuron-methyl (0.5, 5, and 50 ppb) was applied via the
      nutrient solution to the root system, asparagine concentrations increased 3-6
      times in stems roots, and leaves. Metsulfuron-methyl is known to impair the
      synthesis of branched amino acids and, in consequence, protein synthesis. Thus,
      nitrogen consumption was limited, leading to ar accumulation of asparagine. The
      possible use of this physiological response in agricultural practice to identify
      herbicide stress in soybean and to detect low-level residues of sulfonylurea
      herbicides ir the soil is discussed.

PMID- 11305253
TI  - Certification of B-group vitamins (B1, B2, B6, and B12) in four food reference
      materials.
AB  - In 1989, the Community Bureau of Reference started a research program to improve
      the quality of vitamin analysis in food. To achieve this task, vitamin
      methodology was evaluated and tested by interlaboratory studies and the
      preparation of certified reference materials, which will be used for quality
      control of vitamin measurements. The main improvements in methodology were
      achieved by testing and standardizing the extraction condition and enzymatic
      hydrolysis procedures. Results for each individual material are derived from five
      replicate determinations using at least two independent methods: liquid
      chromatography (HPLC) and microbiological assay for vitamins B1, B2, and B6; and
      radioprotein binding and microbiological assays for vitamin B12. The certificate
      of analysis for four reference materials gives mass fraction values for water
      soluble vitamins. These certified values were based on the acceptable statistical
      agreement of results from collaborating laboratories. Certified values with
      uncertainties (mg/kg dry matter) for each CRM are as follows: 4.63 (0.20) and
      4.10 (0.51) for vitamins B1 and B6, respectively, in CRM 121 (wholemeal flour);
      6.51 (0.24), 14.54 (0.3), 6.66 (0.43), and 0.034 (0.003) for vitamins B1, B2, B6,
      and B12, respectively, in CRM 421 (milk powder); 3.07 (0.17) and 4.80 (0.40) for
      vitamins B1 and B6, respectively, in CRM 485 (lyophilized mixed vegetables), and
      8.58 (0.55), 106.8 (2.8), 19.3 1.5), and 1.12 (0.044) for vitamins B1. B2, B6,
      and B12, respectively, in CRM 487 (lyophilized pig liver).

PMID- 11305254
TI  - Modulation of the biosynthesis of some phenolic compounds in Olea europaea L.
      fruits: their influence on olive oil quality.
AB  - The phenolic composition of olive fruits (Olea europaea L.) (cv. Picual,
      Villalonga, Alfafarenca, and Cornicabra) grown in different areas of Spain was
      studied by high performance liquid chromatography-mass spectrometry. Different
      levels of tyrosol, catechin, p-coumaric acid, rutin, luteolin, and oleuropein
      were observed in the different varieties analyzed. Treating the fruit with 0.3%
      Brotomax 50 days after anthesis had a beneficial effect on fruit size, oil
      content, levels of polyphenolic compounds, and Trolox-equivalent antioxidant
      activity (TEAC) in all the varieties analyzed.

PMID- 11305255
TI  - Allium chemistry: synthesis, natural occurrence, biological activity, and
      chemistry of Se-alk(en)ylselenocysteines and their gamma-glutamyl derivatives and
      oxidation products.
AB  - Syntheses are reported for gamma-glutamyl Se-methylselenocysteine (Sa),
      selenolanthionine (16), Se-1-propenylselenocysteine (Gd), Se-2-methyl-2-propenyl
      L-selenocysteine (6e), and Se-2-propynyl-L-selenocysteine (6f). Oxidation of 8a
      and Se-methylselenocysteine (Ga) gives methaneseleninic acid (24), characterized
      by X-ray crystallography, and dimethyl diselenide (25). Oxidation of Se-2
      propenyl-L-selenocysteine (6c) gives allyl alcohol and 3-seleninoalanine (22).
      Compound 22 is also formed on oxidation of 16 and selenocystine (4). Oxidation of
      6d gives 2-[(E,Z)-1-propenylseleno]propanal (36). These oxidations occur by way
      of selenoxides, detected by chromatographic and spectroscopic methods. The
      natural occurrence of many of the Se-alk(en)ylselenocysteines and their gamma
      glutamyl derivatives and oxidation products is discussed. Three homologues of the
      potent cancer chemoprevention agents 6a and 6c, namely 6d-f, were evaluated for
      effects on cell growth, induction of apoptosis, and DNA-damaging activity using
      two murine mammary epithelial cell lines. Although each compound displays a
      unique profile of activity, none of these compounds (Gd-f) is likely to exceed
      the chemopreventive efficacy of selenocysteine Se-conjugates Ga and 6c.

PMID- 11305256
TI  - Inhibition of low-density lipoprotein oxidation by carnosine histidine.
AB  - Carnosine is a beta-alanylhistidine dipeptide found in skeletal muscle and
      nervous tissue that has been reported to possess antioxidant activity. Carnosine
      is a potential dietary antioxidant because it is absorbed into plasma intact.
      This research investigated the ability of carnosine to inhibit the oxidation of
      low-density lipoprotein (LDL) in comparison to its constituent amino acid,
      histidine. Carnosine (3 microM) inhibited Cu2+-promoted LDL (20 of protein/mL)
      oxidation at carnosine/copper ratios as low as 1:1, as determined by loss of
      tryptophan fluorescence and formation of conjugated dienes. Carnosine (6 microM)
      lost its ability to inhibit conjugated diene formation and tryptophan oxidation
      after 2 and 4 h of incubation, respectively, of LDL with 3 microM Cu2+. Compared
      to controls, histidine (3 microM) inhibited tryptophan oxidation and conjugated
      diene formation 36 and 58%, respectively, compared to 21 and 0% for carnosine (3
      microM) after 3 h of oxidation. Histidine was more effective at inhibiting copper
      promoted formation of carbonyls on bovine serum albumin than carnosine, but
      carnosine was more effective at inhibiting copper-induced ascorbic acid oxidation
      than histidine. Neither carnosine nor histidine was a strong inhibitor of 2,2'
      azobis(2-amidinopropane) dihydrochloride-promoted oxidation of LDL, indicating
      that their main antioxidant mechanism is through copper chelation.

PMID- 11305257
TI  - Chemical, microbiological, and AromaScan evaluation of mahi-mahi fillets under
      various storage conditions.
AB  - The quality for mahi-mahi stored at 1.7, 7.2, and 12.8 degrees C for 0, 1, 3, and
      5 days was determined using biogenic amine analysis, microbial counts, and
      sensory evaluation (by a sensory test panel and an AromaScan). Biogenic amines in
      methanol extracts from mahi-mahi samples were analyzed using capillary
      electrophoresis (CE) with ultraviolet detection at 210 nm and a gas
      chromatography (GC) method that can simultaneously determine the contents of
      putrescine, cadaverine, histamine, spermidine, and spermine within 20 min after
      pentafluoropropionic anhydride derivatization. A good correlation R2= 0.99) was
      found between CE and GC methods for detecting histamine in mahi-mahi. Fish
      quality deteriorated and correlated with increasing microbial numbers. Biogenic
      amines may be useful indicators for mahi-mahi quality and safety. AromaScan was
      able to correlate quality changes for mahi-mahi in microbiological and sensory
      analyses.

PMID- 11305258
TI  - Determination of benzoyl peroxide and benzoic acid levels by HPLC during wheat
      flour bleaching process.
AB  - Freshly milled wheat flour has a pale yellow color due to its carotenoids
      content. Benzoyl peroxide is a bleaching agent typically used to give such flour
      a better appearance. This free-radical initiator promotes carotenoids oxidation,
      thereby producing less colored compounds, and benzoic acid is a main final
      product. Samples of wheat flour were treated with 150 ppm of benzoyl peroxide to
      begin a bleaching process, and then subjected to ethyl ether extraction at
      different intervals of time. Benzoyl peroxide and benzoic acid levels in these
      extracts were monitored by means of HPLC in individual experiences. The resulting
      concentration of benzoyl peroxide after 9 days of contact with the bleaching
      agent was 11 ppm, dropping afterward to nondetectable levels. A maximum value for
      benzoic acid of 16 ppm was found after 12 h of bleaching. Subsequently this level
      decreased continuously until reaching a residual value of 6 ppm after 3 months.

PMID- 11305260
TI  - Time for a global strategy to improve the treatment of lung cancer?

PMID- 11305259
TI  - Reversible hepatic coma possibly induced by docetaxel treatment.

PMID- 11305261
TI  - Comment on Katsimbri et al.: endobronchial metastases secondary to solid tumours,
      Lung Cancer.

PMID- 11305262
TI  - Predicting the resting metabolic rate of young Australian males.
AB  - OBJECTIVES: The aims of this study were: (a) to generate regression equations for
      predicting the resting metabolic rate (RMR) of 18 to 30-y-old Australian males
      from age, height, mass and fat-free mass (FFM); and (b) cross-validate RMR
      prediction equations, which are frequently used in Australia, against our
      measured and predicted values. DESIGN: A power analysis demonstrated that 38
      subjects would enable us to detect (alpha = 0.05, power = 0.80) statistically and
      physiologically significant differences of 8% between our predicted/measured RMRs
      and those predicted from the equations of other investigators. SUBJECTS: Thirty
      eight males (chi +/- s.d.: 24.3+/-3.3y; 85.04+/-13.82 kg; 180.6+/-8.3 cm) were
      recruited from advertisements placed in a university newsletter and on community
      centre noticeboards. INTERVENTIONS: The following measurements were conducted:
      skinfold thicknesses, RMR using open circuit indirect calorimetry and FFM via a
      four-compartment (fat mass, total body water, bone mineral mass and residual)
      body composition model. RESULTS: A multiple regression equation using the easily
      measured predictors of mass, height and age correlated 0.841 with RMR and the SEE
      was 521 kJ/day. Inclusion of FFM as a predictor increased both the R and the
      precision of prediction, but there was virtually no difference between FFM via
      the four-compartment model (R = 0.893, SEE = 433 kJ/day) and that predicted from
      skinfold thicknesses (R = 0.886, SEE = 440 kJ/day). The regression equations of
      Harris & Benedict (1919) and Schofield (1985) all overestimated the mean RMR of
      our subjects by 518 - 600 kJ/day (P < 0.001) and these errors were relatively
      constant across the range of measured RMR. The equations of Hayter & Henry (1994)
      and Piers et al (1997) only produced physiologically significant errors at the
      lower end of our range of measurement. CONCLUSIONS: Equations need to be
      generated from a large database for the prediction of the RMR of 18 to 30-y-old
      Australian males and FFM estimated from the regression of the sum of skinfold
      thicknesses on FFM via the four compartment body composition model needs to be
      further explored as an expedient RMR predictor.

PMID- 11305263
TI  - High phosphorus intake only slightly affects serum minerals, urinary pyridinium
      crosslinks and renal function in young women.
AB  - OBJECTIVE: Assessment of the physiological effects of a diet rich in phosphorus
      in young women. DESIGN: Control period I--commercial basic diet containing 1700
      mg P and 1500 mg Ca/day for 4 weeks. Supplementation period--a 6 week high
      phosphorus period of 3008 mg P and 1995 mg Ca/day. Control period II--4 weeks
      washout with basic diet as in period I. SETTING: Institute of Nutritional
      Science, Friedrich Schiller University, Jena. SUBJECTS: Ten healthy women, aged
      20-30y. INTERVENTIONS: Orange juice and tablets, containing supplements of
      Ca5(PO4)3OH and NaH2PO4, totalling 1436 mg elemental phosphorus per day. RESULTS:
      There was an increase of 10.7+/-13.7 pg/ml in serum PTH, a decrease of 0.6+/-0.6
      ng/ml in serum osteocalcin, an increase of 73.6+/-136.6 nmol/mmol creatinine in
      urinary pyridinoline and of 19.3+/-36.0 nmol/ mmol creatinine in urinary
      deoxypyridinoline, and a decrease of 2.6+/-9.3 mg/l in urinary microalbumin. All
      changes were insignificant. There were no changes in serum levels of Ca, PO4 or
      Zn, in serum concentration of 1,25-(OH)2D3, and in urinary beta-2-microglobulin
      excretion. Phosphorus supplementation caused intestinal distress, soft stools or
      mild diarrhoea. CONCLUSIONS: In spite of a high phosphorus supplementation no
      significant changes in bone-related hormones, pyridinium crosslinks as markers of
      bone resorption and parameters of renal function in young women were found.

PMID- 11305264
TI  - Monitoring the adequacy of salt iodization in Switzerland: a national study of
      school children and pregnant women.
AB  - BACKGROUND: Several countries with long-standing salt iodization programs,
      including Switzerland, have recently reported declining and/or low urinary iodine
      (UI) levels in their populations. In Switzerland, in response to studies
      indicating low UI levels in children and pregnant women, the salt iodine level
      was increased in 1998 from 15 to 20 mg/kg. OBJECTIVE: Our objective was to
      evaluate iodine nutrition in a national sample of Swiss school children and
      pregnant women 8 16 months after the increase in the salt iodine level. DESIGN: A
      3-stage probability proportionate to size cluster sampling method was used to
      obtain a representative national sample of 600 children aged 6-12 y and 600
      pregnant women. We then measured UI in both groups, thyrotropin (TSH) in pregnant
      women and thyroid volume by ultrasound to determine goiter prevalence in school
      children. RESULTS: The median UI (range) of the children and pregnant women was
      115 microg/l (5-413) and 138 microg/l (5-1881), respectively. The median blood
      TSH concentration (range) of pregnant women was 0.6 mU/l (0.2-2.1). Based on the
      current WHO/ICCIDD normative data for thyroid volume, none of the children were
      goitrous, using either age/sex-specific or BSA/sex-specific cutoffs. CONCLUSIONS:
      The iodine status of the Swiss population is once again adequate, illustrating
      the value of periodic monitoring and prudent adjustments to the iodine level in
      salt. This approach could serve as a model for countries struggling to maintain
      dietary iodine intake in the face of shifting dietary habits and changes in the
      food supply.

PMID- 11305265
TI  - Determinants of infant growth in the slums of Dhaka: size and maturity at birth,
      breastfeeding and morbidity.
AB  - OBJECTIVE: To investigate the influences of size at birth, breastfeeding and
      morbidity on growth during infancy in poor areas of urban Bangladesh. DESIGN:
      This was a prospective observational study of a cohort of newborn infants
      followed until 12 months of age. SETTING: Slum areas of Dhaka City in Bangladesh.
      SUBJECTS: A total of 1654 newborn infants were enrolled at birth, and follow-up
      was completed for 1207 infants. Repeated anthropometric measurements and
      interviews of caretakers on infant feeding and morbidity were conducted. A mixed
      effects regression method was used for modeling infant growth. RESULTS: After
      adjusting for other variables, mean differences in body weight by birth weight
      and length, small-for-gestational age and prematurity categories remained
      relatively constant throughout infancy. A positive impact of exclusive
      breastfeeding in the first 3 5 months on infant growth was detectable at 12
      months of age. Although the bigger babies in the sample tended to grow relatively
      even bigger; exclusive breastfeeding appeared to counteract this pattern.
      Reported diarrhoea was associated with lower body weights and lengths even after
      adjusting for feeding patterns. CONCLUSIONS: Size at birth has an important role
      in determining growth during infancy. Effective strategies for improving birth
      weight, poorly addressed till now in Bangladesh, are needed. The sustained effect
      on growth and the even more beneficial effect in lighter infants are compelling
      reasons for promotion of exclusive breastfeeding in early infancy.

PMID- 11305266
TI  - Breast-feeding duration and the risk of malignant diseases in childhood in
      Sweden.
AB  - OBJECTIVE: To evaluate childhood cancer in relation to duration of breast
      feeding. SETTING: Sweden. Records from Child Healthcare Centres were scrutinised
      regarding information on breast-feeding and other health-related items. SUBJECTS:
      All children aged 0-14 y with a malignant disease (benign brain tumours included)
      during the time period 1988-91 (n = 962) were identified from the Swedish Cancer
      Register. An equal number of controls matched for sex and age were selected from
      the Swedish Birth Register. RESULTS: Information was obtained for 835 cases and
      860 controls. Overall, duration of breast-feeding did not influence the risk for
      a malignant disease in this age group. However, breast-feeding > or = 1 month
      increased the risk for non-Hodgkin's lymphoma (NHL) yielding an odds ratio (OR)
      5.5 with 95% confidence interval (CI) 1.2-25. Breast-feeding 1 -< 6 months gave
      OR 5.1, CI 1.1-24 and > 6 months gave OR 7.0, CI 1.3-37 with a significant trend
      (P = 0.04). Adjustment for maternal and birth-related co-variates gave similar
      results. For other malignancies no significant changes of the risk were obtained.
      CONCLUSIONS: Overall, no association between duration of breast-feeding and
      childhood malignancies was found except for a significantly increased risk for
      NHL, but this was based on low numbers of cases and needs to be confirmed in
      other investigations.

PMID- 11305267
TI  - Short-term effects of a hypocaloric diet on nitrogen excretion in morbid obese
      women.
AB  - OBJECTIVE: To determine whether the daily pattern of urine excretion of N wastes
      is affected by obesity and very low-calorie diets (VLCD). DESIGN: The plasma
      amino acid, urea and other energy parameters, as well as the urinary excretion of
      total nitrogen, urea and creatinine were studied in obese and normal-weight
      women. The obese women's data were obtained under hospital basal controlled
      conditions (8.1 MJ/day) and after 3 days of VLCD diet (1.9 MJ/day) controls were
      studied only once (5.8 MJ/day). The hourly excretion patterns of total N, urea
      and creatinine were determined from the composition of each bladder voiding.
      SUBJECTS: Twenty morbidly obese and 10 age-matched normal-weight control women.
      RESULTS: Plasma amino acid levels were higher in obese women, which showed a
      limited ability to metabolize amino acid hydrocarbon skeletons. Neither
      differences in the patterns between groups nor total 24 h values for urine volume
      were found. Total N and urea excretion diminished under VLCD diet. Hourly
      creatinine excretion showed a flat pattern and was higher in obese women than in
      the controls, VLCD diet diminished the amount of creatinine excreted in 24 h.
      CONCLUSIONS: The early change in energy availability that the creatinine
      excretion figures reflect may result from the energy conservation mechanisms
      induced in response to energy restriction. The early onset of this effect (3
      days, and the extent of decrease (approximately 19%) also suggest that the impact
      of VLCD on the muscle energy budget of the obese is more marked than usually
      assumed.

PMID- 11305268
TI  - Food and nutritional profile of high energy density consumers in an adult
      Mediterranean population.
AB  - OBJECTIVE: To test if an adult Mediterranean population consumes different food
      volumes while spontaneously ingesting diets of different energy density and to
      estimate which are the food and nutritional profiles of these diets. DESIGN: A
      cross-sectional study of food consumption. SETTING: Faculty of Medicine and
      Health Sciences, Universitat Rovira i Virgili, Reus. SUBJECTS: Five hundred and
      seventy two adult individuals (25 65 y) randomly selected from the population
      census of Reus. INTERVENTION: 24 hour recall method for 3 non-consecutive days
      including one holiday. The population was classified into three groups of
      differing energy densities by simple linear regression analysis. Means were
      compared by ANOVA. RESULTS: Both sexes consume similar food volumes across the
      different levels of energy density. High energy density consumers ingest
      significantly more red meat, olive oil, sweet cereals, cereals and sugars and
      less reduced fat milk, green vegetables and fruit compared to low energy density
      consumers. Male and female high energy density consumers show a significantly
      higher consumption of energy (1686 kJ and 2200 kJ, respectively) (P < 0.001), a
      5.2% (P < 0.001) and 2.3% (P < 0.05) respectively higher energy intake derived
      from fat and a 1.3% (P < 0.05) and 1.3% (P < 0.05) respectively higher energy
      intake derived from saturated fatty acids compared to low energy density
      consumers. CONCLUSIONS: Our adult Mediterranean population normally consumes
      similar food volumes, independently of the energy density ingested. High energy
      dense diets in our population could represent an important health risk because
      they are excessively rich in energy, fats and saturated fatty acids.

PMID- 11305269
TI  - Macronutrient and food intake in the Baltic republics.
AB  - OBJECTIVE: The objective of this study was to describe mean macronutrient and
      food intakes in the Baltic republics, with a particular focus on fat, vegetable
      and fruit consumption. DESIGN: Cross-sectional study. SETTING: Data from surveys
      conducted in Estonia, Latvia and Lithuania in the summer of 1997 were used.
      Information was collected using a 24 h recall of dietary intake and an
      interviewer-administered questionnaire. SUBJECTS: Representative national samples
      of adults were selected. All those with information from the dietary recall were
      included in the study (Estonia: n = 2015; Latvia: n = 2300; Lithuania: n = 2094).
      RESULTS: The mean proportion of energy from fat was high in each country, but
      particularly in Lithuania (44%) and Latvia (42%) compared with Estonia (36%). In
      contrast, percentage energy from carbohydrate, protein and alcohol was higher in
      Estonia. Mean protein intake was generally sufficient if not high in some
      population sub-groups. Median vegetable intakes were very low (<200 g/day) in
      each country, particularly in Latvia. While 78% of the Lithuanian respondents
      consumed vegetables daily, this was the case in only 60% of the Latvian and 48%
      of the Estonian respondents. CONCLUSIONS: This study suggests that there is a
      pressing need to replace high-fat energy dense foods by foods rich in complex
      carbohydrates and dietary fibre, such as vegetables and fruits, in the Baltic
      republics. This could provide the populations with a reduced risk and increased
      protection against non-communicable diseases. These issues will need to be
      tackled through comprehensive food and nutrition policies and health promotion
      campaigns.

PMID- 11305270
TI  - Measured and predicted resting metabolic rate in Italian males and females, aged
      18-59 y.
AB  - OBJECTIVES: To determine the resting metabolic rate in a sample of the Italian
      population, and to evaluate the validity of predictive equations for resting
      metabolic rate (RMR) from the literature in normal and obese subjects. DESIGN:
      Cross-sectional observational study. SETTINGS: Department of Human Physiology and
      Nutrition, University 'Tor Vergata', Rome. SUBJECTS: A total of 320 healthy
      subjects, 127 males and 193 females, aged 18-59 y. METHODS: Weight, height and
      resting metabolic rate by indirect calorimetry were measured. Resting metabolic
      rate was also predicted using equations from the literature. RESULTS: Resting
      metabolic rate (mean s.d.) in normal weight subjects was 7983+/-1007 kJ/24 h
      (males) and 6127 907 kJ/24h (females). Measured RMR and predicted RMR values
      using various equations from the literature were significantly different in males
      and females, except for the Harris-Benedict equation and the Schofield equations.
      Also, in overweight and obese subjects the prediction error was generally larger
      compared to normal-weight subjects for all formulas except for the Harris
      Benedict and Schofield formulas. In overweight and obese males but not in
      females, RMR was lower than in normal-weight subjects after correcting for weight
      and age differences. Stepwise multiple regression of resting metabolic rate
      against weight, height and age in males and females did not reveal a prediction
      formula with a lower prediction error than the Harris-Benedict or Schofield
      formulas and thus was not further explored. CONCLUSIONS: The Harris-Benedict
      formula and the Schofield formula provide a valid estimation of resting metabolic
      rate at a group level in both normal-weight and overweight Italians. However, the
      individual error can be so high that for individual use a measured value has to
      be preferred over an estimated value.

PMID- 11305271
TI  - The Mediterranean score of dietary habits in Chinese populations in four
      different geographical areas.
AB  - OBJECTIVE: To compare the dietary intake of Chinese people living in Pan Yu, Hong
      Kong, San Francisco and Sydney with respect to cardiovascular health, using the
      Mediterranean diet score, examining the effects of age, gender, urbanization and
      acculturation on the diet score. SUBJECTS: A total of 500 men and 510 women in
      Hong Kong were recruited as a territory-wide stratified random sample. Subjects
      were recruited in response to local advertisements for the other three sites: Pan
      Yu, 58 men, 95 women; San Francisco, 166 men, 192 women; Sydney, 95 men, 73
      women. METHOD: Food-frequency questionnaire over a 7 week period. A high/healthy
      score was taken as > or =4 for men and >3 for women, representing a dietary
      pattern beneficial for cardiovascular health. RESULTS: In Hong Kong, more women
      in the middle age group (35-54) had a high score than other age groups, and
      overall more women had high scores than men. In comparing the four geographical
      regions, Pan Yu had the highest number of subjects with high score, and Hong Kong
      had the lowest. With the exception of the younger population and men in Hong
      Kong, the percentage of the population with a high score in all sites is greater
      than among elderly Greeks consuming a more traditional heart-healthy
      Mediterranean diet. CONCLUSION: Considerable variations in Chinese dietary
      patterns exist with respect to age, gender and geographic location. Overall, the
      Chinese diet is comparable to the Mediterranean diet and may be expected to have
      similar health benefits that have been documented for the traditional
      Mediterranean diet.

PMID- 11305272
TI  - [Communication and cooperation between physicians, nurses and patients].

PMID- 11305273
TI  - ["We wish to be committed." Quality of nursing service based on comments at
      change-over].

PMID- 11305274
TI  - Senegal cuts deal for low-cost drugs.

PMID- 11305275
TI  - UN special session to address AIDS.

PMID- 11305276
TI  - US-Mexican border is porous when it comes to AIDS.

PMID- 11305277
TI  - Award recognizes link between poverty and AIDS.

PMID- 11305278
TI  - Mbeki's support eroding.

PMID- 11305280
TI  - Don't knock E-health.

PMID- 11305279
TI  - The effects of hook pattern and kyphotic angulation on mechanical strength and
      apical rod strain in a long-segment posterior construct using a synthetic model.
AB  - STUDY DESIGN: Synthetic spine models were used to compare the effects of hook
      pattern and kyphotic angulation on stiffness and rod strain in long-segment
      posterior spinal constructs. OBJECTIVES: To examine the biomechanical effects of
      hook patterns and kyphotic angulation on long-segment posterior spinal
      constructs. SUMMARY OF BACKGROUND DATA: Kyphotic deformities managed by
      increasing rod diameter and hence construct stiffness have shown decreased
      postoperative loss of correction and hardware complications. The biomechanical
      effects of hook pattern and kyphosis are unknown. METHODS: Spine models of 0
      degrees, 27 degrees 54 degrees sagittal contour, composed of polypropylene
      vertebral blocks and isoprene elastomer intervertebral spacers, representing T3
      T12, were used for biomechanical testing of long-segment posterior spinal
      constructs. Models were instrumented with 6.35-mm titanium rods and one of the
      following hook configurations: 20-hook compression, 16-hook compression, 16-hook
      claw apex-empty,16-hook claw apex-full, or 8-hook claw. Construct stiffness and
      rod strain during axial compression were determined. RESULTS: The compression
      hook patterns provided at least a 45% increase in construct stiffness (P =
      0.013)and a 22% decrease in rod strain (P < 0.0001) compared with those obtained
      with the claw-hook pattern with the best biomechanical performance. When
      analyzing all five hook patterns, there was a 19% decrease in construct stiffness
      and 27% increase in rod strain when progressing from straight alignment to 27
      degrees of sagittal contour (P < 0.0001). Progressing from straight alignment to
      54 degrees decreased construct stiffness by 48% and increased rod strain by 55%
      (P < 0.0001). Construct stiffness was inversely correlated to rod strain in all
      five hook patterns (R2 = 0.82-0.98, P < 0.001). CONCLUSIONS: Using compressive
      hook patterns and decreasing the kyphotic deformity significantly increases
      construct stiffness and decreases rod strain.

PMID- 11305281
TI  - Adding patients to the health equation.

PMID- 11305282
TI  - Sharing the costs of health care.

PMID- 11305283
TI  - Proceedings of the International Conference on Bone Morphogenetic Proteins. June
      7-11, 2000. Lake Tahoe, California, USA.

PMID- 11305284
TI  - Levodopa, ayurveda and Parkinson's disease.

PMID- 11305285
TI  - Aromatase deficiency and estrogen resistance: from molecular genetics to clinic.
AB  - Our knowledge of the physiologic roles of estrogen in women and men has been
      advanced by recent descriptions of mutations disrupting estrogen biosynthesis and
      action. Aromatase deficiency results from autosomal recessive inheritance of
      mutations in the CYP19 gene. It gives rise to ambiguous genitalia in 46,XX
      individuals. At puberty, affected girls have hypergonadotropic hypogonadism, fail
      to develop secondary sexual characteristics, and exhibit progressive
      virilization. The affected 46,XY individuals have normal male sexual
      differentiation and pubertal maturation. These men are extremely tall and have
      eunuchoid proportions with continued linear growth into adulthood, lack of
      epiphyseal closure, and osteoporosis due to estrogen deficiency. Although
      estrogen was shown to be essential for normal sperm production and function in
      mice, its role in fertility is not clear in men. Thus far, one estrogen-resistant
      human, a man with a mutant estrogen receptor-alpha gene, has been described. His
      clinical presentation was similar to that of aromatase-deficient men.

PMID- 11305286
TI  - Incidence of keratoconus in subjects with vernal keratoconjunctivitis: a
      videokeratographic study.
AB  - PURPOSE: To detect the incidence of keratoconus by videography in patients with
      vernal keratoconjunctivitis (VKC) and to evaluate the clinical characteristics of
      VKC associated with keratoconus. DESIGN: a prospective, cross-sectional
      (prevalence) study. PARTICIPANTS: Eighty-two consecutive subjects with the
      diagnosis of VKC. METHODS: Both eyes of VKC subjects were investigated by
      videokeratography in comparison with slit-lamp biomicroscopy and keratometry. To
      detect keratoconus, corneal topography maps were examined with modified
      Robinowitz-McDonnell test. MAIN OUTCOME MEASURES: In this test, maps with central
      corneal power greater than 47.2 diopters and/or the inferosuperior asymmetry
      value greater than 1.4 were considered to have a keratoconus pattern. The
      findings of VKC were also recorded, RESULTS: The distribution of clinical forms
      of VKC were as follows: 46.34% mixed, 43.90% palpebral, and 9.76% limbal types.
      Twenty-six (31.7%) of 82 subjects had complications with keratopathy such as
      pseudo-genontoxon, punctate keratitis, and shield ulcer. Forty-four eyes (26.8%)
      were detected as keratoconus by quantitative evaluation of videokeratography
      maps. 14 eyes (8.5%) by biomicroscopy, and 30 eyes (18.3%) by keratometry. The
      increased incidence of keratoconus was associated with male gender, long-standing
      disease, mixed and palpebral forms, and advanced corneal lesions. CONCLUSIONS:
      The higher incidence of keratoconus in our study compared with the previous
      reports may result from early detection of mild keratoconus by interpretation of
      color-coded videokeratographic maps with a sensitive quantitative method.

PMID- 11305287
TI  - [Mediastinal actinomycosis].
AB  - The history of a 45 year old man is reviewed who was treated with acute
      exacerbations of chronic mediastinitis. During one and a half year the patient
      was examined in different departments of internal medicine, he underwent into
      surgical interventions and several histological and microbiological examinations
      have been done. On the third occasion the bacterium of Actinomyces Israeli proved
      to be the etiologic factor of the disease. Some diagnostic and therapeutic points
      of view of different localization of the illness are discussed.

PMID- 11305289
TI  - [Biological monitoring of oral estroprogestagen contraception].

PMID- 11305290
TI  - Black carp and sick cows.

PMID- 11305288
TI  - Reliability, validity, and responsiveness of general and disease-specific quality
      of life measures in a clinical trial for cytomegalovirus retinitis.
AB  - The objective of this study was to evaluate a questionnaire for assessing general
      and disease-specific quality of life among people with cytomegalovirus (CMV)
      retinitis. Cross-sectional and longitudinal analyses of data from 279 people
      enrolled in the CMV Retinitis Retreatment Trial were used. At baseline,
      Cronbach's alpha and multitrait analysis were used to assess internal consistency
      and discriminant construct validity for scales of general health, vision, and
      treatment impact. Associations of scales with clinical measures of health and
      vision were assessed at baseline with Pearson correlations and t tests, and over
      time with generalized estimating equations regression. Internal consistency
      coefficients ranged from .68 to.88. Criteria for discriminant validity were
      fulfilled for most scales; however, the general health perceptions and energy
      scales were highly correlated. Scales were moderately correlated with clinical
      measures at baseline. Over time, scale scores were associated with Karnofsky
      scores and clinical measures of CMV retinitis and vision. General and CMV
      retinitis-specific quality of life measures appear reliable, valid, and
      responsive.

PMID- 11305291
TI  - U.S. science budget. For all but NIH, the devil is indeed in the details.

PMID- 11305292
TI  - Smithsonian Institution. Plan to close zoo lab draws fire.

PMID- 11305294
TI  - Plant physiology. Philodendrons like it hot and heavy.

PMID- 11305293
TI  - Neuroscience. Location neurons do advanced math.

PMID- 11305295
TI  - Genomics. Canada seeks economic payoff across species.

PMID- 11305296
TI  - Structural biology. Robots enter the race to analyze proteins.

PMID- 11305298
TI  - Astrophysicis. Galaxy mappers detect wiggly cosmic order.

PMID- 11305297
TI  - Structural biology. A plan to release data within six months.

PMID- 11305299
TI  - Cosmology. Big bang's new rival debuts with a splash.

PMID- 11305300
TI  - Paleoclimatology. An orbital confluence leaves its mark.

PMID- 11305301
TI  - Global warming. Rising global temperature, rising uncertainty.

PMID- 11305302
TI  - Global warming. Greenhouse warming passes one more test.

PMID- 11305303
TI  - Acid rain. Long-term data show lingering effects from acid rain.

PMID- 11305304
TI  - Object recognition. Where the brain tells a face from a place.

PMID- 11305305
TI  - Paleontology. Palentological rift in the Rift Valley.

PMID- 11305306
TI  - Paleontology. The case of the 'forged' letter.

PMID- 11305307
TI  - Invasive species. Will black carp be the next zebra mussel?

PMID- 11305308
TI  - Extinction: complexity of assessing risk.

PMID- 11305309
TI  - Tales from the DNA of domestic horses.

PMID- 11305310
TI  - Networked research: an EC model for U.S.?

PMID- 11305311
TI  - Public health. HIV/AIDS treatment for millions.

PMID- 11305312
TI  - Public health. Reducing HIV transmission in developing countries.

PMID- 11305313
TI  - Molecular biology. DNA ends ReQ-uire attention.

PMID- 11305314
TI  - Superconductivity. Toward tunable superconducting electronics.

PMID- 11305315
TI  - Neurobiology. Function following form.

PMID- 11305316
TI  - Physical chemistry. Single molecules rock and roll near the glass transition.

PMID- 11305317
TI  - Sun-climate connections. Earth's response to a variable Sun.

PMID- 11305318
TI  - Neuroscience. A kinase to dampen the effects of cocaine?

PMID- 11305319
TI  - 9th European Workshop on Bacterial Protein Toxins. Abstracts.

PMID- 11305320
TI  - Apoptosis in oncology.
AB  - Apoptosis is a complex process involving a large array of genes and mutation of
      any of these genes may lead to malignancy formation. Re-acquirement of FasL by
      tumor cells may enable them to evade the surveillance of immune system and thus
      contributes to the growth of tumor. Apart from traditional therapies, inducing
      apoptosis of tumor cell by new methods employing death receptor ligands and
      making use of Fas counterattack is also being developed.

PMID- 11305321
TI  - Differential screening and characterization analysis of the egg envelope
      glycoprotein ZP3 cDNAs between gynogenetic and gonochoristic crucian carp.
AB  - Gynogenetic silver crucian carp, Carassius auratus gibelio, is an intriguing
      model system. In the present work, a systemic study has been initiated by
      introducing suppression subtractive hybridization technique into this model
      system to identify the differentially expressed genes in oocytes between
      gynogenetic silver crucian carp and its closely related gonochoristic color
      crucian carp. Five differential cDNA fragments were identified from the
      preliminary screening, and two of them are ZP3 homologues. Moreover, the full
      length ZP3 cDNAs were cloned from their oocyte cDNA libraries. The length of ZP3
      cDNAs were 1378 bp for gyno-carp and 1367 bp for gono-carp, and they can be
      translated into proteins with 435 amino acids. Obvious differences are not only
      in the composition of amino acids, but also in the number of potential O-linked
      oligosaccharide sites. In addition, gyno-carp ZP3 amino acid sequence has an
      unexpected higher identity value with common carp (83.5%) than that with the
      closely related gono-carp (74.7%). The unique homology may be originated from the
      ancient hybridization. Northern blot analysis confirmed that expression of the
      ZP3 gene occurred exclusively in the oocytes. Because O-linked oligosaccharides
      on ZP3 have been demonstrated to play very important roles in fertilization, it
      is suggested that the extra O-linked glycosylation sites may be related to the
      unique sperm-egg recognition mechanism in gynogenesis.

PMID- 11305322
TI  - Partial characterization of the N-linked oligosaccharide structures on P-selectin
      glycoprotein ligand-1 (PSGL-1).
AB  - PSGL-1, a specific ligand for P-, E- and L-selectin, was isolated from in vivo
      [3H]-glucosamine labeled HL-60 cells by a combination of wheat germ agglutinin
      agarose and P- or E-selectin-agarose chromatography. N-linked oligosaccharides
      were released from the purified, denatured ligand molecule by peptide: N
      glycosidase F treatment and, following separation by Sephacryl S-200
      chromatography, partially characterized using lectin, ion-exchange and size
      exclusion chromatography in combination with glycosidase digestions. The data
      obtained suggest that the N-glycans on PSGL-1 are predominantly core-fucosylated,
      multiantennary complex type structures with extended, poly-N-acetyllactosamine
      containing outer chains. A portion of the outer chains appears to be substituted
      with fucose indicating that the N-glycans, in addition to the O-glycans on PSGL
      1, may be involved in selectin binding.

PMID- 11305323
TI  - Hydrogen peroxide-induced changes in intracellular pH of guard cells precede
      stomatal closure.
AB  - Epidermal bioassay demonstrated that benzylamine, a membrane-permeable weak base,
      can mimick hydrogen peroxide (H2O2) to induce stomatal closure, and butyric acid,
      a membrane-permeable weak acid, can partly abolish the H2O2-induced stomatal
      closure. Confocal pH mapping with the probe 5-(and-6)-carboxy
      seminaphthorhodafluor-1-acetoxymethylester (SNARF-1-AM) revealed that H2O2 leads
      to rapid changes in cytoplasmic and vacuolar pH in guard cells of Vicia faba L,
      i. e. alkalinization of cytoplasmic areas occur red in parallel with a decrease
      of the vacuolar pH, and that butyric acid pretreatment can abolish alkalinization
      of cytoplasmic areas and acidification of vacuolar areas of guard cells
      challenged with H2O2. These results imply that the alkalinization of cytoplasm
      via efflux of cytosol protons into the vacuole in guard cells challenged with
      H2O2 is important at an early stage in the signal cascade leading to stomatal
      closure.

PMID- 11305324
TI  - Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling
      pathway in a STAT6 independent manner: implications for cell survival and
      proliferation.
AB  - IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine
      phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated
      blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3' kinase
      in both resting and activated cells. By contrast, association of phosphorylated
      IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although
      both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2
      in B cell blasts. The pattern of IL-4-induced recruitment of p85 and GRB2 to IRS2
      observed in B cells derived from STAT6 null mice was identical to that observed
      for normal mice. While IL-4 alone does not induce activation of MEK, a MEK1
      inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B
      cell blasts. These results demonstrate that costimulation of splenic B cells
      alters IL-4-induced signal transduction independent of STAT6 leading to
      proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts
      is dependent upon the MAP kinase pathway.

PMID- 11305325
TI  - p53-independent upregulation of p21WAF1 in NIH 3T3 cells malignantly transformed
      by mot-2.
AB  - Mot-2 protein is shown to interact with p53 and inhibit its transcriptional
      activation function. Mot-2 overexpressing stable clones of NIH 3T3 cells were
      malignantly transformed, however, they had a high level of expression of a p53
      downstream gene, p21WAF1. The present study was undertaken to elucidate possible
      molecular mechanism(s) of such upregulation. An increased level of p21WAF1
      expression was detected in stable transfectants although an exogenous reporter
      gene driven by p21WAF1 promoter exhibited lower activity in these cells
      suggesting that some post-transcriptional mechanism contributes to upregulation.
      Western analyses of transient and stable clones revealed that upregulation of
      p21WAF1 in stable NIH 3T3/mot-2 cells may be mediated by cyclin D1 and cdk-2.

PMID- 11305326
TI  - Overexpression of gamma-aminobutyric acid transporter subtype I leads to
      susceptibility to kainic acid-induced seizure in transgenic mice.
AB  - Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter, and
      the GABAergic synaptic transmission is normally terminated by the rapid uptake
      through GABA transporters. With transgenic mice ubiquitously overexpressing GABA
      transporter subtype I (GAT1), the present study explored the pathophysiological
      role of GAT1 in epileptogenesis. Though displaying no spontaneous seizure
      activity, these mice exhibit altered electroencephalographic patterns and
      increased susceptibility to seizure induced by kainic acid. In addition, the
      GABA(A) receptor and glutamate transporters are up-regulated in transgenic mice,
      which perhaps reflects a compensatory or corrective change to the elevated level
      of GAT1. These preliminary findings support the hypothesis that excitatory and
      inhibitory neurotransmission, and seizure susceptibility can be altered by
      neurotransmitter transporters.

PMID- 11305327
TI  - Structural components of the nuclear body in nuclei of Allium cepa cells.
AB  - Nuclear bodies have long been noted in interphase nuclei of plant cells, but
      their structural component, origin and function are still unclear by now. The
      present work showed in onion cells the nuclear bodies appeared as a spherical
      structure about 0.3 to 0.8 microm in diameter. They possibly were formed in
      nucleolus and subsequently released, and entered into nucleoplasm. Observation
      through cytochemical staining method at the ultrastructural level confirmed that
      nuclear bodies consisted of ribonucleoproteins (RNPs) and silver-stainable
      proteins. Immunocytochemical results revealed that nuclear bodies contained no
      DNA and ribosomal gene transcription factor (UBF). Based on these data, we
      suggested that nuclear bodies are not related to the ribosome or other gene
      transcription activities, instead they may act as subnuclear structures for RNPs
      transport from nucleolus to cytoplasm, and may also be involved in splicing of
      pre-mRNAs.

PMID- 11305328
TI  - Rice bicoid-related cDNA sequence and its expression during early embryogenesis.
AB  - Bicoid is one of the important Drosophila maternal genes involved in the control
      of embryo polarity and larvae segmentation. To clone and characterize the rice
      bicoid-related genes, one cDNA clone, Rb24 (EMBL accession number: AJ2771380),
      was isolated by screening of rice unmature seed cDNA library. Sequence analysis
      indicates that Rb24 contains a putative amino acid sequence, which is homologous
      to unique 8 amino acids sequence within Drosophila bicoid homeodomain (50%
      identity, 75% similarity) and involves a lys-9 in putative helix 3. Northern blot
      analysis of rice RNA has shown that this sequence is expressed in a tissue
      specific manner. The transcript was detected strongly in young panicles, but less
      in young leaves and roots. This results are further confirmed with paraffin
      section in situ hybridization. The signal is intensive in rice globular embryo
      and located at the apical tip of the embryo, then, along with the development of
      embryo, the signal is getting reduced and transfers into both sides of embryo.
      The existence of bicoid-related sequence in rice embryo and the similarity of
      polar distribution of bicoid and Rb24 mRNA in early embryo development may
      implicates a conserved maternal regulation mechanism of body axis presents in
      Drosophila and in rice.

PMID- 11305329
TI  - Involvement of chromatin and histone acetylation in the regulation of HIV-LTR by
      thyroid hormone receptor.
AB  - The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical
      for viral propagation and pathology. Numerous host factors have been shown to
      participate in the regulation of the LTR promoter. Among them is the thyroid
      hormone (T3) receptor (TR). TR has been shown to bind to the critical region of
      the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier
      transient transfection studies in tissue culture cells have yielded contradicting
      conclusions on the role of TR in LTR regulation, likely due to the use of
      different cell types and/or lack of proper chromatin organization. Here, using
      the frog oocyte as a model system that allows replication-coupled chromatin
      assembly, mimicking that in somatic cells, we demonstrate that unliganded
      heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the
      addition of T3 relieves the repression and further activates the promoter. More
      importantly, we show that chromatin and unliganded TR/RXR synergize to repress
      the promoter in a histone deacetylase-dependent manner.

PMID- 11305330
TI  - Melanocortin-1 receptor gene variants in four Chinese ethnic populations.
AB  - There is strong relationship between melanocortin-1 receptor (MC1R) gene variants
      and human hair color and skin type. Based on a sequencing study of MC1R gene in
      50 individuals from the Uygur, Tibetan, Wa and Dai ethnic populations, we discuss
      the occurrence of 7 mc1r variants consisting of 5 nonsynonymous sites (Val60Leu,
      Arg67Gln, Val92Met, Arg163Gln and Ala299Val) and 2 synonymous sites (C414T and
      A942G), among which C414T and Ala299Val were reported for the first time.
      Confirmation and analysis were also made of 122 individuals at three common point
      mutations (Val92Met, Arg163Gln, A942G) using PCR-SSCP. The frequency of Arg163Gln
      variant varies in the four ethnic populations, with percentage of 40%, 85.0%,
      66.2% and 72.7%, respectively, while those of Val92Met and A942G are roughly
      similar in these four populations. The different environments, migration and
      admixture of various ethnic groups in China might have impact on the observed
      frequency of Arg163Gln.

PMID- 11305331
TI  - Chloroaromatic formation in incineration processes.
AB  - The high-temperature reactions of chlorinated hydrocarbons are reviewed with a
      primary focus on the gas-phase molecular growth chemistry and elementary reaction
      mechanisms leading to the formation of chlorinated benzenes and chlorinated
      polycyclic aromatic hydrocarbons. Recent heterogeneous mechanistic studies of the
      chlorination and condensation of aliphatic hydrocarbons at lower temperatures are
      also summarized. Copper(II) valent species play an important role as catalyst and
      reagent. The main thermal pathways for chlorinated dibenzodioxins and furans have
      been deduced by these laboratory experiments, which try to model the complex
      reality of the post-incineration zone of municipal and hazardous waste
      incinerators.

PMID- 11305332
TI  - Dynamic behaviour of 137Cs contamination in trees of the Briansk region, Russia.
AB  - Seven trees were felled in the Briansk region in 1997. The trees were sectioned
      for sampling, both at different heights and according to year rings, and samples
      were analysed for content of 137Cs. In general, the specific activity of 137Cs
      was much higher in the fresh parts of the three (needles, leaves and twigs) than
      in the core wood. The year ring study showed that 137Cs had penetrated deeply in
      to the trunk, and no peak was detectable in the year ring corresponding to the
      Chernobyl accident in 1986. The specific activity in the trunk wood had a maximum
      at the height corresponding to the growth years at approximately 1986. Neutron
      activation analysis was used to analyse for stable Cs. The results showed that
      the relationship between concentrations of 137Cs and stable caesium is much
      higher in the newer parts of growing trees than in the older parts. Together with
      a tendency of inward migration this leads to a preliminary conclusion that the
      137Cs activity will continue to accumulate in the core wood.

PMID- 11305333
TI  - Seasonal export of phosphorus from a lowland catchment: upper River Cherwell in
      Oxfordshire, England.
AB  - The export of phosphorus from a lowland catchment, the River Cherwell in southern
      England, was measured over a period of 1 year. The results describe total
      phosphorus concentrations in the water and river discharge at 4-day intervals.
      These were used to estimate the load of total phosphorus exported from the
      catchment. These annual loads were compared with exports estimated from sewage
      inputs and diffuse inputs calculated from land-coverage data, with assigned
      phosphorus export coefficients for particular land uses. The method was further
      developed to examine seasonal changes in phosphorus exports by predicting monthly
      losses using annual export coefficients normalised with respect to the relative
      hydraulic runoff for a particular month. The results show a strong seasonal
      dependence of total exports, with retention of phosphorus in the river system in
      the spring to early autumn and release of stored material during the winter. This
      pattern remained true, even with 50% increase in the main land-cover export and a
      similar increase in treated sewage exports.

PMID- 11305334
TI  - Platinum and rhodium distribution in airborne particulate matter and road dust.
AB  - In this work the platinum and rhodium content in the atmosphere of Madrid was
      monitored for 1 year at seven different sites. Samples were taken with medium
      volume PM-10 collectors (< 10 microm) for 48 h and analysed by ICP-MS. The Pt and
      Rh content was dependent on the sampling site, ranging from < 0.1 to 57.1 and <
      0.2 to 12.2 pg m(-3) with a medium value of 12.8 and 3.3 pg m(-3), respectively.
      These results show that the Pt and Rh content in airborne samples depends on the
      traffic density per day and also on medium driving speed. Road dust < 63 microm
      was analysed at the same time and at the same location. The Pt and Rh content at
      the six sites analysed was in the 31-2252 and 11-182 ng g(-1) range with an
      average of 317 and 74 ng g(-1), respectively. The average Pt/Rh ratio obtained
      was 4.3. similar to that obtained for airborne particles (4.0), and agrees with
      that of the more commonly used gasoline car catalyst [J.J. Mooney, Encyclopaedia
      of Chemical Technology (1996) 982]. Platinum distribution as a function of
      particle size in airborne particulate matter was also studied, by sampling with
      two high-volume sample collectors, a five-stage WRAC (from 10 to 65.3 microm and
      total) and a seven-stages PM-10) cascade impactor (from 9 to < 0.39 microm).
      Platinum is associated with a wide range of particle diameters. Due to the
      ultratrace level of Pt in airborne samples, its distribution in the atmosphere
      could not be considered as homogeneous. No trend could be established in Pt
      distribution in the different fractions, except that in most cases the highest
      value of Pt was obtained in the < 0.39-microm fraction. The Pt content was
      usually high in airborne samples when the Pb, Ce, Zr and Hf content was also
      high, thus confirming that the source of these pollutants is from traffic.

PMID- 11305335
TI  - Reduction of fine airborne particulates (PM3) in a small city centre office, by
      altering electrostatic forces.
AB  - A two stage intervention study was carried out to establish the degree to which a
      newly developed, electrostatic air cleaning (EAC) system can improve indoor air
      quality (IAQ) by reducing the number of airborne fine particles. The IAQ and how
      employees in a city centre office (49 m2) perceived it, was monitored from May
      until November 1998. The number of fine particles, PM3 (0.3-3.0 microm); number
      of coarse particles, PM7 (3.0-7.0 microm); number of small positive and negative
      air ions; relative humidity and temperature were recorded in and out of doors. To
      assess the employees' perception of any changes in their work environment, a
      questionnaire was completed. Number of particles, relative humidity and
      temperature were also recorded in a nearby office, equipped with an identical air
      processor, where no interventions were made. The results from the first
      intervention (Stage 1), comparing number of airborne particles outdoors to
      indoors, gave a 19% reduction for PM3 and a 67% reduction for PM7 (P < 0.001).
      The reduction in PM3 was inconsistent and not statistically significant (P =
      0.3). The reduction in PM7 from outdoors and the removal of PM7 created indoors
      was achieved by optimizing the existing air moving equipment. The results from
      the second intervention (Stage 2--with EAC units installed) comparing indoor to
      outdoor values, gave a further reduction in PM3 of 21% (P < 0.001) and a further
      3% reduction for PM7 (P > 0.05). Therefore, at the end of Stage 2, the total
      reductions in particles from outdoors to indoors were 40% for PM3 and 70% for PM7
      (P < 0.001). The Stage 2 results strongly suggest that electrostatic forces,
      created by the EAC unit(s) improved the removal of PM3, with no further
      significant improvement in the reduction of PM7. The questionnaire indicated an
      improvement in the IAQ, as perceived by the employees. The results suggest that
      the EAC system is effective in reducing PM3 and thereby improving IAQ in an urban
      office.

PMID- 11305336
TI  - Exposure of Chironomus riparius larvae to 17alpha-ethynylestradiol: effects on
      survival and mouthpart deformities.
AB  - Evidence from field studies shows that mouthpart deformities in chironomid larvae
      are a sublethal response to pollution. Interest has been shown to use this end
      point in programs for monitoring sediment quality. During laboratory studies,
      however, deformities were induced in only a few single pollutant exposures. These
      deformities develop at the endocrine regulated molting stage and disruption of
      this complex process is likely at the base of their ontogeny. Aiming to clarify
      the processes involved in the rise of such deformities, we tested the effects of
      ethynylestradiol (EE2) in an in vivo lab study. Chironomus riparius larvae were
      exposed to 1, 10 and 100 microg l(-1) EE2 (nominal concentrations). No adverse
      effects on the larvae, for the investigated end-points (survival and deformity
      induction), were found.

PMID- 11305337
TI  - Quantitative structure-property relationships on photodegradation of PCDD/Fs in
      cuticular waxes of laurel cherry (Prunus laurocerasus).
AB  - By the use of the partial least squares (PLS) method and 13 fundamental quantum
      chemical descriptors computed by PM3 Hamiltonian, a OSPR model was developed for
      first order rate constants of photodegradation of 10 PCDD/Fs dissolved in
      cuticular wax from laurel cherry (Prunus laurocerasus) leaves and exposed to
      sunlight. The QSPR showed that photodegradation rates increase with the degree of
      chlorination of the homologues. PCDD/Fs with large values of Q(Cl) (the largest
      positive atomic charge on a chlorine atom in a molecule), Q(O)- (the most
      negative atomic charge on the oxygen atoms in a molecule), and mu (dipole moment)
      tend to photodegrade fastest. PCDD/Fs with large values of E(lumo) (the energy of
      the lowest unoccupied molecular orbital), E(homo) (the energy of the highest
      occupied molecular orbital), and E(lumo) - E(homo) tend to have the lowest
      photodegradation rates.

PMID- 11305338
TI  - Blood lead levels in Jamaican school children.
AB  - Blood lead levels are reported for a total of 421 schoolchildren in 13 schools in
      rural and urban environments in Jamaica, including one highly contaminated
      community. In the rural areas blood lead levels ranged from 3 to 28.5 microg dl(
      1), with a median of 9.2 microg dl(-1); the range and median in the urban schools
      were 4-34.7 and 16.6 microg dl(-1), respectively. Forty-two percent of the rural
      and 71% of the urban blood lead levels exceeded the US Centers for Disease
      Control and Prevention intervention level of 10 microg dl(-1). Except in the
      contaminated area, the relationship between soil lead levels, which in Jamaica
      are in general typical of tropical lateritic soils, and blood lead levels is not
      clear-cut. Very high blood lead levels of 18 to > 60 microg dl(-1) with a median
      of 35 microg dl(-1) were observed among children in the contaminated area, the
      site of a former lead ore processing plant. These high blood lead levels were
      significantly reduced, by the implementation of relatively simple mitigation
      strategies which involved isolation of the lead, education, and a food
      supplementation programme, to levels similar to those observed in the urban
      schools. These values, however, remain higher than are desirable and
      unfortunately, all the sources of lead are not yet identified. The recent
      discontinuation of the use of leaded petrol is expected to result in significant
      reductions in exposure to lead.

PMID- 11305340
TI  - First observation of intersex cyprinids in the Po River (Italy).
AB  - Barbel (Barbus plebejus, Cyprinidae) were captured in the Po River, upstream and
      downstream from the confluence of the Lambro River, a polluted tributary of the
      major Italian watercourse. The gonads of the two groups of barbel have been
      histologically examined, and only the downstream specimens showed histo
      morphological alterations that can be related to the Lambro tributary as a source
      to the main river of endocrine disrupting chemicals, possibly with estrogenic
      effects. In fact, 50% of the barbel captured (8 of 16 fish) in the downstream
      reach showed intersex gonads.

PMID- 11305339
TI  - Wide use of skin-lightening soap may cause mercury poisoning in Kenya.
AB  - In a previous study, we speculated that some of the high mercury levels observed
      in head hair from a total of 14 subjects who resided around Lake Victoria,
      Tanzania, might be attributable to the habitual use of toilet soap containing
      considerable amounts of mercury (Harada et al. Sci Total Environ 1999;227:249
      256). In August 1998, the current study was conducted to investigate if such
      mercury-containing soap was also available in the surroundings of Lake Victoria,
      Kenya, and if so, its toxic effects. A total of nine goldminers, 44 fishermen and
      their families, and 12 residents of Kisumu City, Kenya, volunteered for the
      study. Fourteen types of toilet soap were collected in Kisumu. Total mercury
      content was very significantly higher than in European-made soap (0.47-1.7%, as
      mercury iodide) compared with Kenya-made soap (0.41 x 10(-4)-6.2 x 10(-4)%).
      Indeed, all the subjects with a high hair mercury level (> 36.1 ppm) had made
      habitual use of European-made soap, accompanied by various symptoms, such as
      tremor, lassitude, vertigo, neurosthenia, and black and white blots, suggesting
      inorganic-mercury poisoning. On the other hand, any subject who had used soap
      other than the European-made soap, did not exceed a mercury level of 10 ppm in
      hair that is well within normal limits (Harada et al. Sci Total Environ
      1999:227:249-256). The findings obtained suggest that the mercury-containing soap
      must be barred from circulation without delay, and that the residents' health in
      addition to the environmental pollution in Lake Victoria (Kenya as well as
      Tanzania) should be kept under close observation.

PMID- 11305341
TI  - Exposure to volatile organic compounds for individuals with occupations
      associated with potential exposure to motor vehicle exhaust and/or gasoline vapor
      emissions.
AB  - Workers who work near volatile organic compounds (VOCs) source(s), motor vehicle
      exhausts and/or gasoline vapor emissions, are suspected to be exposed to highly
      elevated VOC levels during their work-time. This study confirmed this suspicion
      and evaluated the work-time exposure VOCs for traffic police officers, parking
      garage attendants, service station attendants, roadside storekeepers and
      underground storekeepers, by measuring the concentrations of six aromatic VOCs in
      workplace air, or personal air and breath samples. For nearly all target VOCs,
      the post-work breath concentrations of the workers were slightly or significantly
      higher than the pre-work breath concentrations, depending on the compound and
      occupation. Furthermore, both the pre- and post-work breath concentrations of the
      workers showed elevated levels compared with a control group of college students.
      The post-work breath concentrations were significantly correlated with the
      personal air concentrations, while the pre-work breath concentrations were not.
      Smoking workers were not always exposed to higher aromatic VOC levels than non
      smoking workers. The breath and personal air concentrations for all the target
      compounds were both higher for underground parking garage attendants than for
      ground-level parking attendants. For all the target compounds except toluene,
      storekeepers exhibited similar levels of exposure for all store types. Print
      shopkeepers recorded the highest toluene exposure.

PMID- 11305342
TI  - Speciation of selenium in plant water extracts by ion exchange chromatography
      hydride generation atomic absorption spectrometry.
AB  - Determination of selenium (Se) speciation in plants is important in studying the
      bioavailability and toxicity of Se in Se-contaminated soil/sediment. In this
      study, we used an anion exchange resin (Dowex 1-10X) to separate Se into non
      amino acid organic Se, Se-amino acids, selenite (Se [IV]) and selenate (Se [VI])
      in a plant (Stanleya pinnata) extract. The hydride generation atomic absorption
      spectrometry (HGAAS) was used to determine concentrations of these Se compounds
      in plant extracts. Results showed that Se compounds can be quantitatively
      separated by the resin column. Recovery of five spiked standard Se compounds
      (trimethylselenonium ion (TMSe+), dimethylselenoxide (DMSeO), selenomethionine
      (Semet), Se [IV] and Se [VII]) in the plant extract ranged from 92.9 to 103%.
      Water extractable Se accounted for 60.4-72.6% of the total Se in the plant. Among
      the soluble Se compounds in the plant extract, Se-amino acids were 73-85.5%, Se
      [VI] ranged from 7.5 to 19.5% and non-amino acid organic Se was less than 7%. Se
      [IV] in most samples was below the detection limit (1 microg/g). This study
      showed that considerable amounts of the accumulated Se [VI] in the plant was
      metabolized to Se-amino acids during growth of the plant.

PMID- 11305343
TI  - Lead and zinc in the Wallsend Burn, an urban catchment in Tyneside, UK.
AB  - This paper examines lead and zinc concentrations in topsoils and stream sediments
      of public access areas in an urban catchment in Tyneside, UK. It examines the
      extent and severity of metal contamination, explores spatial patterns in relation
      to urban and industrial development, and makes inferences about potential metal
      mobility. Total and acetic-acid extractable lead and zinc concentrations, organic
      content and pH were determined on 121 topsoil and 22 stream sediment samples
      using standard laboratory procedures. Using the lowest trigger thresholds for
      total lead and zinc, almost 75% and 91%, respectively, of topsoil samples were
      classified as contaminated; proportions were rather lower for acetic acid
      extractable metals. Similarly, approximately 45% and 95% of stream sediment
      samples were contaminated with lead and zinc, respectively. The spatial
      distribution of metal concentrations was characterized by a hotspot pattern, with
      highest values in central and southern parts of the catchment where there is a
      long urban and industrial history. The potential mobility of zinc is considerably
      greater than that of lead in both topsoils and stream sediments, and for both
      metals is slightly higher in the stream sediments than in the topsoils; both of
      these differences are statistically significant (P < 0.05). The implications of
      the findings in this paper for assessment and monitoring of metal contaminated
      areas are explored.

PMID- 11305344
TI  - Serum selenium concentration in a representative sample of the Canarian
      population.
AB  - The concentration of serum selenium in 395 individuals (187 males + 218 females)
      living in the Canary Islands, Spain was determined by hydride generation atomic
      absorption spectrometry. The mean selenium concentration was 74.7 +/- 25.2
      microg/l ranging between 7.86 and 182.3 microg/l. Twenty-two adults (7.2% of the
      total) had serum selenium concentrations under 45 microg/l. It is widely accepted
      that below this selenium serum concentration (45 microg/l) there is an increased
      risk of cardiovascular disease and cancer. Our results fall within data recently
      published in other Spanish and European regions and are much lower than data
      observed in USA or seleniferous regions. The estimated Se intakes of our
      population were lower than the Recommended Dietary Allowances for American
      people. Individuals from Lanzarote had a mean Se concentration significantly
      higher than individuals from the other islands. This could be attributed to
      differences in Se content of soil and/or differences in dietary habits of the
      populations. Serum selenium concentration did not vary with the sex of the
      subjects. Individuals younger than 14 years old had a serum selenium
      concentration significantly lower than the rest of the individuals. No
      relationship with socio-economic status, educational level, smoking habits,
      physical exercise or beer consumption was found. However, individuals who consume
      wine more than three times a week showed higher selenium concentrations than
      individuals with lower consumption. Also, individuals with consumption above
      seven units of spirit drinks a week had the highest mean selenium concentration.

PMID- 11305345
TI  - Occurrence and fate of linear and branched alkylbenzenesulfonates and their
      metabolites in surface waters in the Philippines.
AB  - Laguna de Bay in the Philippines is one of the largest freshwater lakes in Asia
      and is considered a primary source of drinking water, but also receives daily
      discharges of effluent from both domestic and industrial activities. Branched
      alkylbenzenesulfonates (ABS), which were banned in Europe and withdrawn from the
      market in the U.S. since the mid-1960s, but not in Southeast Asia, and linear
      alkylbenzenesulfonates (LAS) are anionic surfactants used in detergent
      formulations and are therefore main components of effluent discharges. The
      presence of both LAS and ABS in several water streams in the catchment area of
      Laguna de Bay was determined using liquid chromatography-mass spectrometry (LC
      MS). The concentration levels of LAS (1.2-73 and 2.2-102 microg l(-1)) and ABS
      (1.1-75 and 1-66 microg l(-1)) in some tributaries of Laguna de Bay and its
      outlet (Pasig River) to Manila Bay were assessed in December 1999 and March 2000,
      respectively. The LAS/ABS ratio was calculated as an indication of the extent of
      the distribution and fate of these surfactants in the surface water. The nearer
      the location to the metropolitan area of Manila, the higher the levels of LAS and
      ABS detected in the waters. Moreover, the extent of biodegradation was
      investigated by monitoring their alkyl homologue distribution and the presence of
      sulfophenylcarboxylate (SPC) metabolites. Similarly, differences in the levels of
      SPC and the homologues were apparent at the different sampling points.
      Presumably, even the quite recalcitrant ABS form SPCs under the conditions
      present in Southeast Asia. Since wastewater treatment facilities are not well
      established in developing countries like the Philippines, the call for the use of
      environmentally friendly chemicals is of even higher significance.

PMID- 11305346
TI  - 137Cs availability for soil to understory transfer in different types of forest
      ecosystems.
AB  - A quantitative analysis of 137Cs bioavailability in forest soils in the long term
      after the Chernobyl NPP accident based on a 3-year (1996-1998) investigation is
      presented. Five forest sites with different trees, composition and properties of
      soil were studied to identify factors determining radiocaesium transfer to
      different understory species. The following parameters were investigated: 137Cs
      activity concentrations and its speciation in various horizons of forest soil,
      accumulation of this radionuclide by different species of understory vegetation
      and distribution of root biomass in the soil profile. It has been shown that one
      decade after the deposition maximum 137Cs activity in soil of the experimental
      sites considered is located in different soil layers dependent on moisture
      regime, characteristics of litter and soil properties. A linear dependence
      between aggregated transfer factors for different species and groups of species
      of understory vegetation and exchangeable and available fractions of radiocaesium
      in soil was found. The vertical distribution of 137Cs activity, percentage of
      exchangeable radiocaesium in each horizon of litter and soil, as well as
      distribution of root systems (mycelia) over the soil profile are key factors
      governing variations in the availability of 137Cs for transfer to all forest
      understory components.

PMID- 11305347
TI  - Fact, fiction, and function: mythmaking and the social construction of ecstasy
      use.
AB  - Myths and folklore about drugs represent important aspects of user subcultures.
      This paper explores Ecstasy users' perceptions about drug folklore as it relates
      to the social relationships of drug user lifestyles. The data for the study were
      collected through in-depth interviews with 50 current or former Ecstasy users in
      Northern Ireland. The findings indicate that although some Ecstasy users perceive
      the folklore to be an accurate reflection of reality others report that social
      relations among users change with continued usage, occur within selected venues,
      or are influenced by greater cultural relations that characterize mainstream
      society.

PMID- 11305348
TI  - Where you live and where you shoot: suggestive data from Valencia, Spain.
AB  - Residence appears to exert influence over choices of venues for injection among
      intravenous drug users (IDUs) in Valencia, Spain. While living in their parents'
      homes, young IDUs may resort to high-risk venues for injection, particularly
      chutaderos in which used needles and syringes are often reused. Residence
      patterns of young IDUs in Spain may be highly similar to residence of IDUs in
      Italy and Puerto Rico, which also have AIDS epidemics dominated by IDUs rather
      than men who have sex with men. Intervention in these places needs to take
      contextual factors of residence into account for effective prevention of HIV
      infection.

PMID- 11305349
TI  - Methods for estimating prevalence of opiate use as an aid to policy and planning.
AB  - Public health planning continues to be troubled by the uncertainty of the extent
      of hidden drug use. Methods for estimating the prevalence of opiate use are
      discussed. These include multisource enumeration, death multiplier, multiple
      indicator, and capture-recapture methods. The feasibility and data requirements
      for each of these methods is illustrated for the first time in an Irish context.
      Estimates presented are the result of years of intensive collaboration between
      previously unconnected government, health, and legal agencies. Finally, the
      implications of the methods and their results for the planning and provision of
      medical and social policy are highlighted and discussed.

PMID- 11305350
TI  - Computerized projection of future heroin epidemics: a necessity for the 21st
      century?
AB  - Although U.K. has seen significant advances in knowledge since the onset of its
      last major heroin epidemic in the early 1980s, it is still the case that most
      assessments of the extent of drug misuse are based on old data. Recognition of
      this problem is evidenced by the many attempts elsewhere to reduce the lag
      between data collection and data use in such programs as DAWN, ADAM, and PULSE
      CHECK. Such programs are an improvement, but they are nevertheless still
      estimates of unknown reliability, and still about the past rather than about the
      future. Building on the pioneering work of Hunt and Chambers in the 1970s, the
      authors present the output of a computerized model that attempts to forecast the
      heroin epidemics of the future.

PMID- 11305351
TI  - Normal drug use: ethnographic fieldwork among an adult network of recreational
      drug users in inner London.
AB  - A key debate in late 1990s Britain is the "normalization" of illicit drug use
      among young people. This qualitative research study explores recreational drug
      use (mainly cannabis and cocaine) among an adult friendship network in an inner
      London neighborhood. It finds that the use of these drugs is accepted as a normal
      and routine aspect of daily life. In addition to patterns of drug consumption and
      drug dealing, some aspects of risk perception are also described. Adults are
      neglected in current UK drug policy debates. "Normal" adult recreational drug use
      poses the need for a new public health policy agenda for the new century.

PMID- 11305352
TI  - Cross-cultural approaches to harm reduction research: some considerations on the
      Brazil experience.
AB  - Harm reduction initiatives for drug users comprise a range of approaches,
      including drug-user treatment, advocacy for changes in drug policy, needle
      exchange programs, bleach distribution, and broad-based interventions that focus
      on both safer drug use and less risky sexual behaviors. In many developing
      nations, harm reduction is a relatively new strategy, which focuses almost
      exclusively on the connections between drug use and the spread of HIV infection.
      In Brazil, harm reduction programs are few, and little has been documented about
      their scope, experience, and effectiveness. This paper reviews the status of
      Brazilian harm reduction initiatives in general, with a specific focus on lessons
      learned from the conduct of cross-national research in Rio de Janeiro. The study
      demonstrated the feasibility of implementing a community-based prevention program
      among an at-risk population of cocaine users in Brazil, and in other countries
      where there is little tradition of research with out-of-treatment drug users.
      Finally, the paper addresses aspects of the harm reduction movement that tend to
      hamper its progress in both developed and developing nations.

PMID- 11305353
TI  - Monitoring synthetic drug markets, trends, and public health.
AB  - The Drugs Information and Monitoring System (DIMS) in The Netherlands is a
      toxicoepidemiologic monitor of drug markets that was established in 1992. Its
      main focuses are to identify the compounds of synthetic drugs, describe
      prevalence and trends, and identify health risks. Here we discuss the insights
      gained in the Ecstasy market, based on the weekly testing of more than 100 drug
      samples, and key information of synthetic drug users delivering drug samples and
      personnel participating in the DIMS network. Pills used as Ecstasy may contain a
      wide variety of compounds. The percentage of samples containing MDMA increased
      slowly reaching almost 75% in 1996, but decreasing sharply in 1997. Amphetamines
      ("speed" and "ice") and experimental varieties were found in at least one third
      of the pills. Origins and effects of this development are discussed, as well as
      the risk assessment. In 1998 the percentage of MDMA pills increased more than
      ever before, indicating among other things that consumers prefer the conventional
      product. However, the use of "speed" and other drugs may also be stimulated by
      the decrease in 1997 of the percentage of MDMA pills. With more new types of
      drugs likely in the next century, a monitor such as DIMS provides important
      surveillance and data for public health and preventive aims.

PMID- 11305354
TI  - Reawakening the dragon: changing patterns of opiate use in Asia, with particular
      emphasis on China's Yunnan province.
AB  - Asian countries adjacent to the Golden Triangle and their neighbors have
      witnessed an evolution in "drug abuse" from traditional opium smoking to heroin
      eating, smoking, and finally heroin injection. A recent study of 630 heroin users
      was conducted in China's Yunnan Province, located close to the Golden Triangle.
      Data collected between August 1997 and February 1998 indicate injecting heroin
      users, in comparison to noninjectors, were more likely to have used drugs for a
      longer period of time, and to use drugs more frequently everyday. Other major
      differences existed between urban and rural subjects, especially highlighting
      differences between men and women. Women comprised a much higher proportion of
      urban subjects than rural subjects. Rural injectors were much more likely to be
      male, but urban injectors were almost evenly split between men and women. The
      emerging epidemic of heroin use in China and the continuing substance abuse
      problem in the United States provide an opportunity for collaborative research of
      mutual benefit.

PMID- 11305355
TI  - Infectious diseases and public health: risk-taking behavior during participation
      in the Swiss program for a medical prescription of narcotics (PROVE).
AB  - The medically controlled prescription of narcotics program (PROVE) followed a
      uniform protocol from January 1, 1994 until December 31, 1996. The program
      included 800 slots for heroin prescription, 200 slots for intravenous methadone
      prescription, and 200 slots for intraveneous morphine. Admission criteria were
      age 20 and above, minimum 2-year duration of daily heroin consumption, failure in
      at least two previous treatments, and documented social and/or health deficits.
      There was a very high seroprevalence of hepatitis B (73%) and hepatitis C (82%)
      among the 1035 entrants. The rate of HIV (15%) was also high compared with
      prevalence of infection in other therapy programs (methadone program, inpatient
      therapy). The prevalence of HIV and hepatitis B/C increased with the duration of
      drug dependence and cocaine use. During treatment, use of street heroin and
      cocaine could be reduced substantially. After 18 months of continued
      participation in the program, 74% of patients reported no illegal heroin
      consumption, and the rate of cocaine abstinence increased from 15% at entry to
      41%. Significant declines in visits to the drug scene, illegal income, and needle
      sharing were also observed. The high prevalence of HIV and hepatitis B and C
      confirm that a group of drug dependence with severe medical problems was reached
      in accordance with the admission criteria for the studies. During treatment, a
      significant reduction in risk-taking behavior was observed in a target population
      of heroin-dependent persons who failed in previous treatments.

PMID- 11305356
TI  - A comparison of HIV risk behaviors between new and long-term injection drug
      users.
AB  - The purpose of this study was to characterize the injection and sexual risk
      behaviors of a cohort of active drug injectors who have initiated injection
      within the past 4 years and to compare their behaviors with the risk behaviors of
      long-term injectors who have been injecting drugs since 1984. A stratified,
      network-based sample was used to recruit injection drug users from the streets in
      Miami-Dade, Florida. After screening for eligibility, which included a urine test
      to confirm current drug use, participants were administered a structured
      questionnaire that included basic demographic information, drug-use history, and
      HIV risk behavior practices. Both injector groups displayed a high level of HIV
      injection risk behavior. Although new initiates into injection demonstrated lower
      risk behavior than long-term injectors at the first injection episode, the
      current risk behavior between new and long-term injectors is similar.

PMID- 11305357
TI  - Genetic transformation of major wine grape cultivars of Vitis vinifera L.
AB  - We have developed an Agrobacterium-mediated transformation system for a number of
      important grapevine cultivars used in wine production. Transgenic plants were
      obtained for the seven cultivars: Cabernet Sauvignon, Shiraz, Chardonnay,
      Riesling, Sauvignon Blanc, Chenin Blanc and Muscat Gordo Blanco. Embryogenic
      callus was initiated from anther filaments and genotypic differences were
      observed for initiation and subsequent proliferation with Chardonnay responding
      most favourably to culture conditions. The transformation system allowed the
      recovery of germinating transgenic embryos 10-12 weeks after Agrobacterium
      inoculation and plants within 18 weeks. Examination of the expression patterns of
      the green fluorescent protein gene under the control of the CAMV35S promoter in
      leaf tissue of transgenic plants showed that for up to 35% of plants the pattern
      was not uniform. The successful transformation of a genetically diverse group of
      wine grape cultivars indicates that the transformation system may have general
      application to an even wider range of Vitis vinifera cultivars.

PMID- 11305359
TI  - Efficiency and stability of high molecular weight DNA transformation: an analysis
      in tomato.
AB  - The efficiency of the binary bacterial artificial chromosome (BIBAC) vector for
      Agrobacterium-mediated stable transfer of high molecular weight DNA into plants
      was tested in tomato. Several variables affecting transformation efficiency were
      examined including insert size, Agrobacterium genetic background, and the
      presence of additional copies of the virG, virE1 and virE2 genes. It was found
      that a helper plasmid containing extra copies of virG was an absolute requirement
      for obtaining tomato transformants with the BIBAC. MOG101 with the virG helper
      plasmid was found to be the most efficient strain for transfer of high molecular
      weight DNA (150 kb). Selected high molecular weight DNA transformants were
      advanced several generations (up to the R4) to assess T-DNA stability. This
      analysis showed that the T-DNA was stably maintained and inherited through
      several meioses regardless of whether it was in the hemizygous or homozygous
      state. Expression of a selectable marker gene within the T-DNA was also examined
      through several generations and no gene silencing was observed. Thus, the BIBAC
      is a useful system for transfer of large DNA fragments into the plant genome.

PMID- 11305358
TI  - Use of human CD4 transgenic mice for studying immunogenicity of HIV-1 envelope
      protein gp120.
AB  - HIV-1 envelope protein, gp120, is a major immunogenic protein of the AIDS virus.
      A specific feature of this protein is its interaction with the receptor protein,
      human CD4, an important component of the immune system. This interaction might
      affect the immunogenic properties of the gp 120 and modulate the immune response
      towards HIV. To test this hypothesis we used human CD4-transgenic mice for
      immunization with gp120. The dynamics of the immune response towards gp120, CD4
      and other proteins was followed. The results show that the primary immune
      response to gp120 (two weeks) developed somewhat faster in CD4-transgenic mice
      versus non-transgenic mice. Both animals, however, ultimately mounted the same
      level of response over time. The primary immune response to gp120 when complexed
      with soluble CD4 before the immunization, developed similarly in both groups. The
      secondary immune response was earlier and markedly stronger in non-transgenic
      mice compared with the transgenic mice where a less efficient memory response to
      gp120 was observed. The ability of gp120 to directly interact with CD4+ helper
      lymphocytes appears to affect the humoral response towards this antigen.
      Moreover, these effects illustrate how viral modulation of these cells may in
      turn lead to potentially different states of immunological equilibrium.

PMID- 11305360
TI  - A one-step gene amplification system for use in cultured mammalian cells and
      transgenic animals.
AB  - Gene amplification is widely used for the production of pharmaceuticals and
      therapeutics in situations where a mammalian system is essential to synthesise a
      fully active product. Current gene amplification systems require multiple rounds
      of selection, often with high concentrations of toxic chemicals, to achieve the
      highest levels of gene amplification. The use of these systems has not been
      demonstrated in specialised mammalian cells, such as embryonic-stem cells, which
      can be used to generate transgenic animals. Thus, it has not yet proved possible
      to produce transgenic animals containing amplified copies of a gene of interest,
      with the potential to synthesise large amounts of a valuable gene product. We
      have developed a new amplification system, based around vectors encoding a
      partially disabled hypoxanthine phosphoribosyltransferase (HPRT) minigene, which
      can achieve greater than 1000-fold amplification of HPRT and the human growth
      hormone gene in a single step in Chinese hamster-lung cells. The amplification
      system also works in mouse embryonic-stem cells and we have used it to produce
      mice which express 30-fold higher levels of human protein C in milk than obtained
      with conventional transgenesis using the same protein C construct. This system
      should also be applicable to large animal transgenics produced by nuclear
      transfer from cultured cell lines.

PMID- 11305361
TI  - Efficient co-transformation of Nicotiana tabacum by two independent T-DNAs, the
      effect of T-DNA size and implications for genetic separation.
AB  - The co-transformation of a single plant genome with two independent T-DNA regions
      provides opportunities for genetic separation in subsequent generations. In an
      effective strategy, co-delivery events must form a high proportion of the total
      transformed population. In this study, using the model plant species tobacco
      (Nicotiana tabacum), it was shown that the frequency of co-transformation within
      a given To population could be as high as 100% and this was found to be
      dependent, at least in part, on designing the plasmid vectors so that the kbp
      size of the first selected T-DNA region was >2-fold that of the designated T-DNA
      region for co-transfer. Overall, 40-50% of To lines demonstrated the capacity for
      segregational separation of co-transformed T-DNA regions. Hence, the estimate of
      the required number of total transformants for such an independent strategy may
      seem to be as little as 2-fold that for a conventional, single T-DNA strategy,
      but we strongly temper such estimates with indications that high co
      transformation frequencies may be associated with a higher incidence of linkage.
      In this co-transformation study we used a single (Agrobacterium) strain system in
      which a single binary plasmid contained either two or three T-DNA regions, each
      with a selectable marker. This arrangement could reveal that 'read-through'
      events within the Agrobacterium cells, resulting in the co-transfer of adjacent T
      DNA regions as a single linked unit, accounted for up to 20% of co-transformed
      plant lines. Such read-through co-delivery appeared to be more frequent from the
      'supervirulent' EHA101 A. tumefaciens strain, compared to the 'ordinary' LBA4404
      strain. By using the binary plasmid with three selectable T-DNA regions, we have
      been able to consider the frequency of co-integration of a third independent T
      DNA within a T0 subpopulation of co-transformants. This was found to be higher
      than expected. These observations were applied to the co-transfer of (unwanted)
      plasmid backbone sequences and showed that screening against such sequences may
      add a significant factor in achieving the desired, final genotype.

PMID- 11305362
TI  - Statistical parameters in behavioral tasks and implications for sample size of
      C57BL/6J:129S6/SvEvTac mixed strain mice.
AB  - Most mixed strain progeny from gene-knockout experiments typically originate from
      C57BL/6J and one of the 129 substrains, frequently 129S6/SvEvTac. The results of
      this behavioral survey suggest that C57BL/6J:129S6/SvEvTac mixed strain mice are
      amenable to behavioral testing. The variability in behavioral tasks for subjects
      arising from this mixed strain genetic background does not preclude screening
      with a battery of behavioral tests. With clues provided by a screen of mixed
      strain subjects, follow-up analyses with isogenic, congenic, or F1 hybrid animals
      may be targeted to specific behavioral themes.

PMID- 11305363
TI  - Sorting of glycoprotein B from human cytomegalovirus to protein storage vesicles
      in seeds of transgenic tobacco.
AB  - As part of ongoing studies into the use of plant expression systems for making
      human therapeutic proteins, we have successfully expressed the major
      glycoprotein, gB, of human cytomegalovirus (HCMV) in transgenic tobacco plants.
      Viral glycoprotein was detectable in the protein extracts of mature tobacco seeds
      using neutralizing and non-neutralizing monoclonal antibodies specific for gB.
      Although several mammalian proteins have been expressed in tobacco, localization
      of these proteins in transgenic tobacco tissue has not been extensively examined.
      The objective of this study was to identify the site(s) of recombinant gB
      deposition in mature tobacco seeds. Using immunogold labelling and electron
      microscopy, we found specific labelling for gB in the endosperm of transgenic
      seeds, with gB localized almost exclusively in protein storage vesicles (PSV).
      This occurred in seeds that were freshly harvested and in seeds that had been
      stored for several months. These data indicate that gB behaves like a plant
      storage protein when expressed in tobacco seeds, and provide further support for
      the suitability of plants for producing recombinant proteins of potential
      clinical relevance.

PMID- 11305365
TI  - G-protein-mediated signaling and its control in macrophages and mammalian cells.
AB  - G-protein coupled receptor (GPCR) in various cell types exert its effects through
      heterotrimetic GTP-binding proteins (G-proteins). The interaction of specific
      ligand or agonists with CPCR transuces signal and enhances gene expression,
      mitogen activated protein kinase (MAP kinase) activation, and thus regulates cell
      proliferation, differentation, and motility. Abnormal signaling or prolonged
      activation of G-protein signaling pathways blocks normal functioning of various
      cells and tissues of our body. New insights into the mechanisms governing the
      specificity and temporal regulation of G-protein signaling pathways have been
      provided by the recent discovery of GTPase-activating proteins (GAPs) and RGS
      proteins (regulators of G-protein signaling). Different molecular biological
      approaches are now being employed to study the G-protein-mediated signaling and
      its control in various mammalian cells. Recent developments on the activation of
      phagocytic cells, especially macrophages, via ligation or cross-linking of GPCR
      and their postreceptor ligation effect against several intramacrophage pathogens
      are also discussed.

PMID- 11305366
TI  - Penicillin fermentation: mechanisms and models for industrial-scale bioreactors.
AB  - Even after many years of research and industrial practice, the production of
      penicillin G in fed-batch fermentation by Penicillium crysogenum continues to
      attract research interest. There are many reasons: the commercial and therapeutic
      importance of penicillin and its derivatives, the complexity of cell growth, and
      the impact of engineering variables, the last of which are significant in large
      bioreactors but are not yet fully understood. Extensive research has generated
      new information on the mechanisms of cellular reactions and morphological
      features of the mycelia and their role in the synthesis of the product. Given a
      choice of mechanisms, models of different degrees of complexity, for both
      cellular differentiation and bioreactor performance, have been proposed. The more
      complex models require and provide more information. They are also more difficult
      to evaluate and apply in automatic control systems for production-scale
      bioreactors. The present review considers the evolution of recent knowledge and
      models from this perspective.

PMID- 11305367
TI  - Allelopathic bacteria and their impact on higher plants.
AB  - The impact of allelopathic, nonpathogenic bacteria on plant growth in natural and
      agricultural ecosystems is discussed. In some natural ecosystems, evidence
      supports the view that in the vicinity of some allelopathically active perennials
      (e.g., Adenostoma fasciculatum, California), in addition to allelochemicals
      leached from the shrub's canopy, accumulation of phytotoxic bacteria or other
      allelopathic microorganisms amplify retardation of annuals. In agricultural
      ecosystems allelopathic bacteria may evolve in areas where a single crop is grown
      successively, and the resulting yield decline cannot be restored by application
      of minerals. Transfer of soils from areas where crop suppression had been
      recorded into an unaffected area induced crop retardation without readily
      apparent symptoms of plant disease. Susceptibility of higher plants to
      deleterious rhizobacteria is often manifested in sandy or so-called skeletal
      soils. Evaluation of phytotoxic activity under controlled conditions, as well as
      ways to apply allelopathic bacteria in the field, is approached. The allelopathic
      effect may occur directly through the release of allelochemicals by a bacterium
      that affects susceptible plant(s) or indirectly through the suppression of an
      essential symbiont. The process is affected by nutritional and other
      environmental conditions, some may control bacterial density and the rate of
      production of allelochemicals. Allelopathic nonpathogenic bacteria include a wide
      range of genera and secrete a diverse group of plant growth-mediating
      allelochemicals. Although a limited number of plant growth-promoting bacterial
      allelochemicals have been identified, a considerable number of highly diversified
      growth-inhibiting allelochemicals have been isolated and characterized. Some
      species may produce more than one allelochemical; for example, three different
      phyotoxins, geldanamycin, nigericin, and hydanthocidin, were isolated from
      Streptomyces hygroscopicus. Efforts to introduce naturally produced
      allelochemicals as plant growth-regulating agents in agriculture have yielded two
      commercial herbicides, phosphinothricin, a product of Streptomyces
      viridochromogenes, and bialaphos from S. hygroscopicus. Many species of
      allelopathic bacteria that affect growth of higher plants are not plant specific,
      but some do exhibit specificity; for example, dicotyledonous plants were more
      susceptible to Pseudomonas putida than were monocotyledons. Differential
      susceptibility of higher plants to allelopathic bacteria was noted also in much
      lower taxonomical categories, at the subspecies level, in different cultivars of
      wheat, or of lettuce. Therefore, when test plants are employed to evaluate
      bacterial allelopathy, final evaluation must include those species that are
      assumed to be suppressed in nature. The release of allelochemicals from plant
      residues in plots of 'continuous crop cultivation' or from allelopathic living
      plants may induce the development of specific allelopathic bacteria. Both the
      rate by which a bacterium gains from its allelopathic activity through utilizing
      plant excretions, and the reasons for the developing of allelopathic bacteria in
      such habitats, are important goals for further research.

PMID- 11305364
TI  - Size matters: use of YACs, BACs and PACs in transgenic animals.
AB  - In 1993, several groups, working independently, reported the successful
      generation of transgenic mice with yeast artificial chromosomes (YACs) using
      standard techniques. The transfer of these large fragments of cloned genomic DNA
      correlated with optimal expression levels of the transgenes, irrespective of
      their location in the host genome. Thereafter, other groups confirmed the
      advantages of YAC transgenesis and position-independent and copy number-dependent
      transgene expression were demonstrated in most cases. The transfer of YACs to the
      germ line of mice has become popular in many transgenic facilities to guarantee
      faithful expression of transgenes. This technique was rapidly exported to
      livestock and soon transgenic rabbits, pigs and other mammals were produced with
      YACs. Transgenic animals were also produced with bacterial or P1-derived
      artificial chromosomes (BACs/PACs) with similar success. The use of YACs, BACs
      and PACs in transgenesis has allowed the discovery of new genes by
      complementation of mutations, the identification of key regulatory sequences
      within genomic loci that are crucial for the proper expression of genes and the
      design of improved animal models of human genetic diseases. Transgenesis with
      artificial chromosomes has proven useful in a variety of biological, medical and
      biotechnological applications and is considered a major breakthrough in the
      generation of transgenic animals. In this report, we will review the recent
      history of YAC/BAC/PAC-transgenic animals indicating their benefits and the
      potential problems associated with them. In this new era of genomics, the
      generation and analysis of transgenic animals carrying artificial chromosome-type
      transgenes will be fundamental to functionally identify and understand the role
      of new genes, included within large pieces of genomes, by direct complementation
      of mutations or by observation of their phenotypic consequences.

PMID- 11305368
TI  - Molecular taxonomy of the genus Chlorobium.
AB  - This review summarizes molecular studies on the taxonomy of the genus Chlorobium.
      Furthermore, we try to introduce a comprehensive view of how joining traditional
      phenotypic-based taxonomy with the current molecular approaches leads to a more
      natural classification. Moreover, we introduce the current insights that
      molecular techniques have brought to the detection and identification of
      nonisolated Chlorobium strains in their environments.

PMID- 11305369
TI  - What's new in the treatment of melanoma?

PMID- 11305370
TI  - What's new in hidradenitis suppurativa?

PMID- 11305371
TI  - What's new in acne inversa (alias hidradenitis suppurativa)?

PMID- 11305372
TI  - Helicobacter pylori and rosacea.

PMID- 11305373
TI  - Some thoughts on rosacea.

PMID- 11305374
TI  - Balneology today.

PMID- 11305375
TI  - Cutaneous manifestations of inflammatory bowel disease.

PMID- 11305376
TI  - What's going on in rosacea?

PMID- 11305377
TI  - Dermatoscopy in the diagnosis of pigmented skin lesions: a new semiology for the
      dermatologist.
AB  - Dermatoscopy or epiluminescence microscopy (ELM), is a noninvasive method that
      enables clinicians to evaluate fully--by means of a magnified oil immersion
      diascopy--numerous morphological features, not visible with the naked eye, which
      enhance the diagnosis of nearly all pigmented skin lesions. In recent years, a
      burst of research activity in this topic has been carried out, dealing with
      different aspects, and new frontiers, of this technique. First, a continuous
      refinement of dermatoscopic terminology is undertaken, paying particular
      attention to the diagnostic performance of dermatoscopy at peculiar anatomical
      sites and to the building of different dermatoscopic algorithms aimed at a
      simplified diagnosis of melanoma, even for less experienced observers. Another
      point of interest concerns the possible role of dermatoscopy in the pre-operative
      assessment of melanoma thickness. Finally, promising data about the role of
      digital equipment in the follow up of melanocytic skin lesions as well as in the
      automated diagnosis of pigmented skin lesions have been recently reported. This
      paper should enable readers to become familiar with the procedure and terminology
      of ELM in the diagnosis of pigmented skin lesions encouraging a greater
      understanding of different methods (pattern analysis, algorithms) in the
      diagnosis of melanoma using ELM.

PMID- 11305378
TI  - Epidemiology of sexually transmitted infections and human immunodeficiency virus
      in Europe.
AB  - Sexually transmitted infections and HIV in Europe present considerable social and
      medical problems and are not always adequately controlled. The recent trends for
      sexually transmitted infections and HIV in Western and Eastern Europe are
      reviewed.

PMID- 11305379
TI  - Pruritic urticarial papules and plaques of pregnancy in twin and triplet
      pregnancies.
AB  - BACKGROUND: Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a
      common dermatosis of unknown aetiology. Multiple pregnancies occur frequently in
      most reported series of PUPPP and increased abdominal distension has been
      considered a factor in its causation. OBJECTIVES: To determine the frequency of
      PUPPP in twin and triplet pregnancies. METHODS: A retrospective review of all the
      records of patients delivered of twin or triplet pregnancies over an 18-month
      period at a busy general maternity hospital. RESULTS: One hundred and thirty
      eight women delivered twins, four of whom developed PUPPP (2.9%). Fourteen women
      delivered triplet pregnancies, two of whom developed PUPPP (14%). Four of these
      six multiple pregnancies were conceived by in vitro fertilization. CONCLUSIONS:
      The reported rate of PUPPP in single pregnancies is 1 in 200 (0.5%). Our findings
      suggest that multiple pregnancies are at a higher risk of developing this
      cutaneous eruption with 2.9% of twin and 14% of triplet pregnancies affected in
      our study.

PMID- 11305380
TI  - Methotrexate in psoriasis: 26 years' experience with low-dose long-term
      treatment.
AB  - OBJECTIVE: To evaluate the efficacy, safety and side-effects of methotrexate
      (MTX) in psoriasis. DESIGN: A 26-year retrospective study. SETTING: Department of
      Dermatology, Leipzig University, Leipzig, Germany. PATIENTS: One hundred and
      fifty-seven patients with extensive plaque psoriasis, erythrodermic, pustular and
      arthropathic forms, were treated with low-dose methotrexate (15-20 mg maximum
      weekly dosage [Weinstein schedule]), the majority for long-term periods. The mean
      cumulative dose was 3394 mg, the mean duration 237 weeks. RESULTS: The effect of
      MTX treatment was good in 76%, moderate in 18% and poor in 6% of subjects; 61%
      experienced side-effects, most frequently due to liver function abnormalities,
      bone marrow suppression, nausea, gastric complaints and hair loss. In 20% of
      cases the subjects were forced to discontinue therapy; 9% refused therapy due to
      physical and psychological discomfort, 2% wanted to become pregnant, 16% were
      lost to follow-up, 6% died from multimorbidity and old age. Three subjects (2%)
      developed cancer of the lung, breast or cervix uteri, possibly in relation to
      long-term MTX treatment. Altogether there were no deaths or life-threatening side
      effects attributable to MTX treatment, and no cases of progressive liver
      cirrhosis apart from two extensive skin necroses due to overdosage
      (misunderstanding, suicidal attempt) that were treated successfully with
      citrovorum factor. CONCLUSION: Low-dose MTX (<15-20 mg/week) is an effective
      therapy for extensive and severe forms of psoriasis if patients are selected
      carefully and monitored regularly, particularly with respect to liver and bone
      marrow toxicity. This helps to reduce severe side-effects even during long-term
      treatment. Drug interactions must be avoided. MTX therapy according to the
      guidelines is relatively safe and still has a place in the systemic treatment of
      psoriasis with 40 years of experience and an acceptable safety record.

PMID- 11305381
TI  - The natural history of hidradenitis suppurativa.
AB  - AIM: To investigate aspects of the natural history of hidradenitis. BACKGROUND:
      The natural history of hidradenitis suppurativa (HS) is not well known. There is
      incomplete published data on the average age of disease onset, progression of the
      disease, average monthly incidence and duration of boils, and factors that
      relieve or exacerbate disease symptoms. STUDY DESIGN: Questionnaire-based survey
      among HS patients identified from hospital records of three hospitals in
      Nottinghamshire, UK. RESULTS: One hundred and ten of 156 questionnaires (70.5%)
      were returned, 93 from females and 17 from males. The average patient's age was
      40.1 years and the average reported age of disease onset was 21.8 years. At the
      time of the survey patients had suffered an average disease duration of 18.8
      years. Most patients (98 of 110) still had experienced active disease within the
      past year. There was some evidence that in women the condition has a tendency to
      ease or subside after the menopause. Forty-four per cent of women felt that their
      condition was aggravated by menstruation. Thirty-eight per cent of patients gave
      a positive family history of the disorder. The average duration of painful boils
      was 6.9 days. In addition, 62% of patients acknowledged the presence of
      permanently painful boils that failed to subside. Patients developed a median of
      two boils per month. Factors that could aggravate the condition were primarily
      sweating or heat, stress or fatigue and tight clothing or friction. Factors that
      could improve the condition consisted largely of a variety of medical treatments
      and a number of life-style measures, such as swimming or baths. Twenty-four per
      cent of patients had failed to find anything at all to help their condition,
      despite an average disease duration of almost 19 years. CONCLUSIONS: The study
      highlights several of the factors that make HS one of the most distressing
      dermatological diseases, such as the average monthly incidence of painful
      lesions, their average duration and the chronicity of the disease. It seems
      striking that the mean duration of an HS boil (6.9 days) roughly equals the
      duration of an average course of antibiotics. The postulated response of HS to
      oral antibiotics may thus simply have its explanation in the natural history of
      the condition itself.

PMID- 11305382
TI  - An open study of efficacy and safety of long-term treatment with mometasone
      furoate fatty cream in the treatment of adult patients with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated
      by the presence of microorganisms and often responds well to treatment with
      potent corticosteroids. However, the long-term use of potent topical
      corticosteroids are accompanied by side-effects such as skin atrophy. OBJECTIVE:
      To study the effect and safety of prophylactic treatment with mometasone furoate
      fatty cream (contains hexylene glycol) for 6 months in patients with atopic
      dermatitis. RESULTS: Sixty-one of 68 (90%) patients were still free of their
      disease after 6 months of twice weekly treatment and only one showed possible
      treatment related signs of skin atrophy. The number of Staphylococcus aureus and
      Pityrosporum ovale were significantly reduced in cleared patients. CONCLUSIONS:
      Mometasone furoate fatty cream is effective and safe both for treatment and as a
      prophylaxis in patients with atopic dermatitis.

PMID- 11305383
TI  - Clearance of ichthyosis linearis circumflexa with balneophototherapy.
AB  - We report a 13-year-old boy suffering from severe ichthyosis linearis
      circumflexa. Evidence of hair shaft abnormalities and impaired immunity could not
      be found. The patient was treated with salt water baths and artificial UVB
      radiation (balneophototherapy) 3-5 times weekly. After 40 treatments with
      balneophototherapy the skin lesions were almost completely cleared and
      maintenance UVB monotherapy was performed twice weekly for 2 months. After 4
      months, however, the disease relapsed. Balneophototherapy presents a potentially
      effective and well tolerated phototherapeutic option for ichthyosis linearis
      circumflexa. As only short periods of remission may be expected, intermittent
      balneophototherapy would be probably necessary to control the disease.

PMID- 11305384
TI  - The Merkel cell carcinoma: survival and oncogene markers.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare and malignant tumour. Survival
      data and prognostic factors are scarce. AIM: To investigate the usefulness of
      biological markers to predict the prognosis for these aggressive tumours.
      METHODS: C-myc oncoprotein and proliferation was analysed in specimens from 13
      patients with MCC, treated between 1983 and 1997. The average age at presentation
      was 68.3 years. Overall follow-up ranged from 14 to 158 months, with a mean of
      68.2 months. Specimens were analysed by immunohistochemistry for proliferation
      (mib-1) and flow cytometry for oncogene activity (c-myc). RESULTS: The median
      positivity was 52% for the c-myc oncogene and 50% for proliferation, but these
      did not correlate to survival as analysed by the Kaplan-Meier method. Other
      parameters such as median age at presentation, sex, site of tumour and adjuvant
      radiotherapy were also analysed, but none were found to be significant.
      CONCLUSIONS: This study showed that neither c-myc oncogene activity or mitotic
      index in MCC can be related to patient survival.

PMID- 11305385
TI  - Acute Crohn's colitis with lobular panniculitis--metastatic Crohn's?
AB  - One of the common lesions in Crohn's colitis is erythema nodosum, a septal
      panniculitis that may appear before diagnosis or in conjunction with flare up. We
      report a case of Crohn's colitis where the presenting sign was neutrophilic
      lobular panniculitis with few granulomas. The possibility that this case
      represents a forme fruste of metastatic Crohn's is suggested. As skin biopsies
      are not usually performed by gastroenterologists in erythema nodosum-like skin
      lesions in Crohn's patients it may well be that the incidence of lobular
      panniculitis is higher than reported in the literature.

PMID- 11305386
TI  - Intratracheal metastasis from malignant melanoma.
AB  - Malignant melanoma is increasing in incidence in most countries. Distant
      metastases are common but intratracheal metastasis is extremely rare. We report a
      54-year-old man who presented with increasing dyspnoea. Symptomatic treatment for
      asthma had been of no effect. Bronchoscopy showed that trachea was nearly
      occluded by a tumoral mass, and biopsy proved this to be a metastasis of
      malignant melanoma. The man's breathing difficulties disappeared after local
      laser therapy, but 2 months later he presented with symptoms of multiple brain
      metastases.

PMID- 11305387
TI  - Lupus erythematosus-like lesions in a carrier of X-linked chronic granulomatous
      disease.
AB  - Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease.
      Carrier status of CGD has been reported in association with lupus erythematosus
      type lesions. A 35-year-old woman, mother of a child with X-linked CGD presented
      an 8-year history of erythematous plaques with an arciform pattern on the upper
      trunk, back and arms. The nitroblue tetrazolium test revealed the carrier status
      of the patient. Haematological, biochemical and immunological tests (including
      ANA, DNA, SSA-Ro, SSB-La, RNP, SM and Jo1 antibodies) were normal or negative
      except for a polyclonal hypergammaglobulinaemia with high serum IgA. Histological
      examination showed a papillary and perifollicular lymphohistiocytic infiltrate.
      Direct immunofluorescence was negative. We report a female carrier of X-linked
      CGD who developed clinical subacute lupus erythematosus-like lesions. We review
      the literature and discuss the pathogenetic mechanisms involved in the condition.

PMID- 11305388
TI  - Successful treatment of angiosarcoma of the scalp by intralesional cytokine
      therapy and surface irradiation.
AB  - An 88-year-old woman presented to us with angiosarcoma of the scalp that had
      developed over a 6-month period following previous trauma. Despite explicit
      information concerning the extremely malignant potential of the tumour the
      patient refused any surgical intervention. However, she agreed to receive local,
      intralesional interferon alpha-2b and interleukin-2 therapy. After partial
      remission of the tumour, the intralesional cytokine injections were combined with
      surface radiotherapy. This combination therapy led to a 2-year remission of both
      the tumour and sonographically suspicious cervical lymph nodes. Apart from the
      typical, moderate side-effects of interferon alpha-2b and interleukin-2 the
      therapy was well tolerated. In conclusion, in our limited experience
      intralesional cytokine therapy--alone as well as in combination with surface
      irradiation--seems to be an alternative therapeutic option for patients who is
      not a candidate for surgery.

PMID- 11305389
TI  - Pemphigus vulgaris and disseminated nocardiosis.
AB  - Infectious diseases, in particular septicaemia from Staphylococcus aureus,
      Proteus vulgaris and Pseudomonas aeruginosa, are the most severe and frequent
      complications for the immunosuppressive therapy of pemphigus. Infection by
      Nocardia asteroides in subjects with pemphigus vulgaris is rare. We report the
      sixth case found of such an association; the subject died of disseminated
      nocardiosis while receiving steroids and immunosuppressive drugs, 4 years after
      being diagnosed with chronic pemphigus vulgaris.

PMID- 11305390
TI  - Digital gangrene: a rare skin symptom in systemic lupus erythematosus.
AB  - A case of digital gangrene in a patient with systemic lupus erythematosus without
      secondary anti-phospholipid syndrome is reported. The acute onset of the
      necrotizing acrovasculitis occurred without a history of Raynaud's phenomenon.
      Preceding symptoms of the systemic lupus erythematosus were arthritis,
      photosensitivity, alopecia and anorexia. Despite the seriousness of the acute
      episode the patient achieved an excellent outcome.

PMID- 11305391
TI  - Continuous terbinafine or pulse itraconazole: a comparative study on
      onychomycosis.

PMID- 11305392
TI  - A novel treatment for acne vulgaris and rosacea.

PMID- 11305393
TI  - Rosacea and Helicobacter pylori: interference of systemic antibiotic in the study
      of possible association.

PMID- 11305394
TI  - Balneophototherapy--combined treatment of psoriasis vulgaris and atopic
      dermatitis with salt water baths and artificial ultraviolet radiation.

PMID- 11305395
TI  - Systemic sarcoidosis revealed by the coexistence of scar and subcutaneous
      sarcoidosis.

PMID- 11305396
TI  - Generalized naevus spilus: a rare entity?

PMID- 11305397
TI  - Changing patterns of visual impairment.

PMID- 11305398
TI  - Neuropsychological outcome at adolescence of very preterm birth and its relation
      to brain structure.
AB  - Neuropsychological outcome at 14 to 15 years of age of a cohort of 75
      participants (39 male, 36 female) born at <33 weeks' gestation was investigated.
      Research was conducted parallel to a recent MRI study by Stewart and colleagues
      which reported that 55% of this cohort had evidence of brain abnormality. One aim
      of the study was to compare neuropsychological function in those very preterm
      children with and without MRI abnormality. Compared to a control sample of term
      adolescents, very preterm participants had impairment only on a measure of word
      production. On measures of attention, memory, perceptual skill, and visuomotor
      and executive function, the adolescents born very preterm performed in the normal
      range, whether or not they had evidence of MRI abnormality. Our findings are
      encouraging as the neuropsychological consequences of damage to the very preterm
      brain, still evident on MRI at 14 to 15 years of age, appear to be minor.

PMID- 11305399
TI  - Safety profile and efficacy of botulinum toxin A (Dysport) in children with
      muscle spasticity.
AB  - Botulinum toxin A (BTX-A) is widely used in the management of muscle spasticity
      in children. However, at present the dose of BTX-A for a given patient is
      selected empirically. The aim of this study is to provide dosage guidelines that
      are based on risk/benefit assessment. This was a multicentre retrospective study
      of the safety profile and efficacy of BTX-A in children with chronic muscle
      spasticity. Data in 758 patients who received a total of 1594 treatments were
      analysed (mean age 7.2 years; 429 males, 329 females). Spastic cerebral palsy
      (CP) was the most common diagnosis (94% of the study sample). Of all treatments
      7% resulted in adverse events; incidence was related to the total dose rather
      than the dose calculated on the basis of body weight. The highest incidence of
      adverse events was observed in patients who received >1000 IU of BTX-A per
      treatment session. The odds of an adverse event was 5.1 times greater for this
      group of patients than for those who had 250 IU or less (p<0.001). A good overall
      response to treatment was reported in 82% and treatment goals were fully or
      partially achieved in 3% and 94% of participants respectively. More patients in
      the highest dose group reported functional deterioration. Interestingly,
      multilevel treatments resulted in a better response than single-level treatments
      (odds ratio 1.7, 95% CI 1.3 to 2.2,p=0.001).

PMID- 11305400
TI  - Regional cerebral blood flow in weight-restored anorexia nervosa: a preliminary
      study.
AB  - Twenty-one individuals (19 females, two males) with teenage-onset anorexia
      nervosa (AN), 19 of whom were weight restored, were assessed using single-photon
      emission computed tomography (SPECT) 7 years after onset of AN, at a mean age of
      22 years. For comparison we recruited a younger group without neuropsychiatric
      disorder (mean age 9:8 years; five females, four males) who underwent SPECT at
      follow-up after an operation for coarctation of the aorta or because of lymphatic
      leukaemia. Ethical considerations precluded the study of regional cerebral blood
      flow (rCBF) in participants with completely normal development. The group with AN
      showed marked hypoperfusion of temporal, parietal, occipital, and orbitofrontal
      lobes compared to the contrast group. rCBF was not correlated to body mass index
      in any of the groups. Results suggest that, even long after re-feeding has
      occurred, AN may be associated with moderate to severe cerebral blood flow
      hypoperfusion in the temporoparietal (or temporoparietooccipital) region and in
      the orbitofrontal region. A limitation of the study is that the young contrast
      group in this study could be expected to have a higher global rCBF than the group
      with AN. However, this should not significantly affect the relative values used
      in this study.

PMID- 11305401
TI  - Landau-Kleffner syndrome: course and correlates with outcome.
AB  - The presenting characteristics of 18 (11 female, seven male) children with Landau
      Kleffner syndrome (LKS) were studied with respect to course and outcome of their
      condition at a mean length of 67 (SD 46) months' follow-up. All had regression of
      receptive language (mean age of onset 4 years 9 months) and electrical status
      epilepticus in sleep (ESES). Length of ESES correlated strongly with length of
      period between onset of illness and onset of recovery (p<0.006) and also with
      eventual receptive (p<0.001) and expressive (p<0.007) language. Behaviour during
      the acute phase was severely affected in nine children and associated with
      frontal lobe discharges in awake EEGs (p<0.004). Age at onset was not correlated
      with outcome. All children had impaired short-term memory at follow-up. Three
      children had language outcome within the normal range. No child with ESES lasting
      longer than 36 months had normal language outcome. These data lend support for
      intervention in ending ESES by 36 months using multiple subpial transection (MST)
      if steroids are ineffective or cause unacceptable side effects.

PMID- 11305402
TI  - Multiple subpial transection in Landau-Kleffner syndrome.
AB  - We have considered multiple subpial transection (MST) as a treatment option for
      Landau-Kleffner syndrome (LKS) for the past 6 years. The effect of this technique
      on language and cognitive ability, behaviour, seizures, and EEG abnormalities is
      analysed here. Five children (4 males, 1 female; aged 5.5 to 10 years) underwent
      MST with sufficiently detailed pre- and postoperative data for analysis.
      Behaviour and seizure frequency improved dramatically after surgery in all
      children. Improvement in language also occurred in all children, although none
      improved to an age-appropriate level. All five had electrical status epilepticus
      in sleep (ESES) before surgery, which was eliminated by the procedure. One child
      has had an extension of his MST due to the recurrence of ESES and accompanying
      clinical deterioration with good effect. An attempt is made to set the effect of
      MST against the natural history of the condition. MST is an important treatment
      modality in LKS, although the timing of this intervention and its effect on final
      language outcome remains to be defined.

PMID- 11305403
TI  - Factors influencing ambulation in myelomeningocele: a cross-sectional study.
AB  - A consecutive series of 53 children with myelomeningocele (mean age 7.6, range
      3.2 to 11.4 years) was assessed in order to see if the children with motor
      paresis of the lower limbs achieved the expected level of ambulation, and if not,
      to identify possible causative factors. Methods used were clinical examination of
      orthopaedic and neurological status, information from medical reports, and
      documentation of orthoses use. Functional skills were documented and energy
      expenditure was examined. Thirty-one of 53 children had reached the expected
      ambulation considered possible according to their motor paresis, whereas 22 of
      the 53 performed worse than expected. Balance disturbances, occurrence of
      spasticity in knee and hip joints, and number of shunt revisions made differed
      significantly between the groups that achieved and did not achieve expected
      ambulation. Functional skills of mobility differed significantly between two
      muscle-function levels in children who had walking ability. Energy expenditure
      was higher in the non-achieving group than in the group who achieved expected
      ambulation in each of the muscle-function levels. Results show that children with
      similar muscle paresis exhibit different ambulatory function. This indicates the
      importance of a close analysis of other factors which may cause ambulation to
      deteriorate in order to predict future ambulation in children with
      myelomeningocele.

PMID- 11305404
TI  - Compliance with home rehabilitation therapy by parents of children with
      disabilities in Jews and Bedouin in Israel.
AB  - Among key points in making progress and succeeding with a therapeutic programme
      for children with disabilities is parental compliance with the regime for their
      child. The purpose of this study was to evaluate factors influencing compliance
      with home therapy in the Jewish and Bedouin populations. Data were collected by
      structured questionnaires. A total of 193 families participated (84% response
      rate) with children who ranged in age from 6 months to 6 years (mean age at first
      visit to the centre was 9.5 years in Jews and 16.1 years in Bedouin). Compliance
      was significantly lower among the Bedouin. Multivariate regression analysis
      showed that the strongest contributory factor in lack of compliance was being
      Bedouin. The second factor was intensity of questioning destiny, indicating that
      parents with these feelings may be less likely to comply with therapeutic
      regimes. Other factors which were associated with compliance were parents'
      education and socioeconomic status: lower levels on these dimensions corresponded
      with lower parental compliance. These results were illuminated by a trial
      intervention programme for Bedouin families which involved telephone contact,
      translation facilities, and detailed explanations during visits to the centre.
      Intervention increased the compliance rate of the Bedouin appointments with
      specialists to 76% (91 of 120 appointments) thereby reaching similar levels to
      those of the Jewish group. These preliminary results indicate that the strong
      association between non-compliance and being Bedouin may be due to factors of
      communication, and that the Bedouin are receptive to therapeutic interventions
      when communicated in their own language.

PMID- 11305405
TI  - Gabapentin as add-on therapy in children with refractory partial seizures: a 24
      week, multicentre, open-label study.
AB  - The efficacy and safety of gabapentin as add-on therapy for refractory partial
      seizures in 237 children, aged 3 to 12 years were evaluated over a 6-month
      period. All children received gabapentin at 24 to 70 mg/kg/day. Efficacy
      variables included the percent change in seizure frequency and the responder rate
      (defined as those patients who showed >50% reduction in seizure frequency). For
      all partial seizures, the median percent change in seizure frequency was -34% and
      the overall responder rate was 34%. Simple partial seizures showed a median
      reduction of -53%; complex partial seizures, -38%; and secondarily generalized
      tonic-clonic seizures, -35%. Thirteen patients (5%) withdrew during the 6-month
      period because of adverse events. Concurrent antiepileptic medication remained
      unchanged in 185 patients (78%), was decreased in 27 (11%), and increased in 25
      (11%) patients. This 6-month follow-up study has demonstrated that gabapentin was
      well tolerated and appeared to show a sustained efficacy in a large population of
      children with refractory partial and secondarily generalized tonic-clonic
      seizures.

PMID- 11305406
TI  - Cervical spinal cord injury following cephalic presentation and delivery by
      Caesarean section.
AB  - We describe a term infant with an acute spinal cord injury following emergency
      Caesarean section. Foetal movements were normal on the day that the mother was
      admitted for postterm induction of labour. Caesarean section was performed
      because of foetal distress and failure to progress during labour. The initial
      clinical picture suggested acute birth asphyxia. The presence of a high cervical
      spine injury became more obvious as the clinical picture evolved over the next 7
      days. A discontinuity of the cervical spinal cord at C4-5 was confirmed on MRI.
      Spontaneous respiration failed to develop and intensive care was withdrawn on day
      15. No evidence of trauma, or a vascular, neurological, or congenital anomaly of
      the cervical spinal cord was found at post mortem. The absence of a similar case
      following cephalic presentation and Caesarean section made bereavement
      counselling of the parents especially difficult.

PMID- 11305407
TI  - Energy requirements of spasticity.
AB  - Direct measurement of energy expended by spasticity in children with severe
      spastic quadriparesis is difficult. Insertion of an intrathecal baclofen pump in
      a 13-year-old boy with severe spasticity and profound mental retardation resulted
      in an estimated 30 to 40% decrease in his spasticity. As he had been on a
      carefully calculated ketogenic diet and fed by gastrostomy, his precise caloric
      intake was known. Decrease in spasticity, on the same caloric intake, led to
      marked weight gain. Reduction of 100 calories intake resulted in new weight
      stability. It was possible therefore, to estimate indirectly energy used by his
      spasticity. This 100 calories, representing 34% of calories above his resting
      energy requirement, corresponded to an independently estimated 30 to 40% of
      caloric expenditure of his spasticity. It was concluded that when calculation of
      calories is critical, energy utilization by spasticity must be taken into
      consideration.

PMID- 11305408
TI  - Review of four tests of gross motor development.

PMID- 11305409
TI  - Cerebrospinal fluid neuropeptide Y in Prader-Willi syndrome.

PMID- 11305410
TI  - Abnormal aluminium metabolism in two siblings with progressive CNS calcification.

PMID- 11305411
TI  - Expression and hypoxic regulation of angiopoietins in human astrocytomas.
AB  - Vascular endothelial growth factor (VEGF) is a major inducer of tumor
      angiogenesis and edema in human astrocytomas by its interaction with cognate
      endothelial-specific receptors (VEGFR1/R2). Tie1 and Tie2/Tek are more recently
      identified endothelial-specific receptors, with angiopoietins being ligands for
      the latter. These angiogenic factors and receptors are crucial for the maturation
      of the vascular system, but their role in tumor angiogenesis, particularly in
      astrocytomas, is unknown. In this study, we demonstrate that the angiopoietin
      family member Ang1 is expressed by some of the astrocytoma cell lines. In
      contrast to VEGF, Ang1 is down regulated by hypoxia. Ang2 was not overexpressed.
      Expression profiles of low-grade astrocytoma specimens were similar to those of
      normal brain, with low levels of Ang1, Ang2, and VEGF expression. Glioblastoma
      multiforme expressed higher levels of Angl, but not to the same degree as
      pseudopalisading astrocytoma cells around necrotic and hypoxic zones expressed
      VEGF, as shown in previous studies. Ang2 expression in the highly proliferative
      tumor vascular endothelium was also increased, as was phosphorylated Tie2/Tek.
      The expression profile of these angiogenic factors and their endothelial cell
      receptors in human glioblastomas multiforme was similar to that in a transgenic
      mouse model of glioblastoma multiforme. These data suggest that both VEGF and
      angiopoietins are involved in regulating tumor angiogenesis in human
      astrocytomas.

PMID- 11305412
TI  - Decreased cyclin B1 expression contributes to G2 delay in human brain tumor cells
      after treatment with camptothecin.
AB  - DNA damage produces delayed mitosis (G2/M delay) in proliferating cells, and
      shortening the delay sensitizes human malignant glioma and medulloblastoma cells
      to cytotoxic chemotherapy. Although activation of the cyclin-dependent kinase
      CDC2 mediates G2/M transition in all tumor cells studied to date, regulation of
      CDC2 varies between tumor types. Persistent hyperphosphorylation of kinase and
      reduced cyclin expression have been implicated as mediators of treatment-induced
      G2 delay in different tumor models. To evaluate regulation of G2/M transition in
      human brain tumors, we studied the expression and/or activity of CDC2 kinase and
      cyclins A and B1 in U-251 MG and DAOY medulloblastoma cells after their treatment
      with camptothecin (CPT). Synchronized cells were treated during S phase, then
      harvested at predetermined intervals for evaluation of cell cycle kinetics,
      kinase activity mRNA, and protein expression. CPT produced G2 delay associated
      with decreased CDC2 kinase activity and cyclin B1 expression. Kinase activity was
      associated with CDC2 bound to cyclin B1, not cyclin A, in both cell lines. Cyclin
      A mRNA and protein expression were reduced after CPT treatment; however,
      decreased protein expression was short lived and moderate in the glioma and
      primitive neuroectodermal tumor/medulloblastoma cells, respectively. We conclude
      that G2 delay is a common response of brain tumor cells to chemotherapy with
      topoisomerase I inhibitors and that a mechanism of this delay may be reduced
      expression of cyclin B1.

PMID- 11305413
TI  - Inhibitory effect of epigallocatechin-gallate on brain tumor cell lines in vitro.
AB  - We investigated the effect of epigallocatechin-gallate (EGCG), the main
      constituent of green tea polyphenols, on human glioblastoma cell lines U-373 MG
      and U-87 MG, rat glioma cell line C6, and rat nonfunctioning pituitary adenoma
      cell line MtT/E. Cell viability was determined by assay with 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and the extent of
      apoptosis was studied by flow cytometric analysis. Apoptosis was also
      characterized by morphology using fluorescent microscopy. The role of insulin
      like growth factor-I (IGF-I) was studied by assay with MTT, immunohistochemistry,
      and immunoradiometric assay. After 72-h exposure, a statistically significant
      loss of viability (P = < 0.0001) was observed at concentrations of 12.5, 25, 50,
      and 100 microg/ml in U-373 MG cells and U-87 MG cells. EGCG at concentrations of
      50 microg/ml and higher significantly reduced the viability of C6 cells. EGCG
      inhibited viability of MtT/E cells only at a concentration of 100 microg/ml.
      Quantitative study by flow cytometry demonstrated that lower doses of EGCG (12.5,
      25, 50 microg/ml) induced apoptosis in U-373 MG, U-87 MG, and C6 cells; however,
      only the highest dose (100 microg/ml) induced apoptosis in MtT/E cells. Compared
      with other cell lines, MtT/E cells showed stronger IGF-I immunoreactivity.
      Neutralization of IGF-I with an antihuman IGF-I antibody reduced viability of the
      cell lines. It can be concluded that EGCG has an inhibitory effect on malignant
      brain tumors, and IGF-I may be involved in the effects of EGCG.

PMID- 11305414
TI  - Adult medulloblastoma: multiagent chemotherapy.
AB  - In this study, the records of 17 adult patients with medulloblastoma treated with
      craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed
      for progression-free survival, overall survival, and toxicity, and the patients
      were compared with each other and with similarly treated children and adults.
      Records of patients treated at 3 institutions were reviewed. Seventeen
      medulloblastoma patients (11 female, 6 male) with a median age of 23 years
      (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT)
      plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were
      infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten
      patients presented with hydrocephalus, and 7 of them were shunted. Eight patients
      had gross total resection, 7 had subtotal resection (>50% removed), and 2 had
      partial resection (<50% removed). Postoperatively, 3 patients had positive
      cytology and 3 had positive spinal MRI. Five patients were classified as good
      risk and 12 were classified as poor risk (Chang staging system). Ten patients
      were treated with the "Packer protocol," consisting of CSRT plus weekly
      vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven
      patients were treated with the Pediatric Oncology Group (POG) protocol,
      consisting of alternating courses of cisplatin/etoposide and
      cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed,
      with all 8 relapsing at the primary site. Other relapse sites included the
      leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free
      survival (Kaplan-Meier) for all patients was 48 months (95% confidence interval,
      >26 months to infinity). Median relapse-free survival for patients on the Packer
      protocol was 26 months, and for those on the POG regimen was 48 months (P =
      0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were
      relapse-free on the POG regimen. Two patients relapsed during chemotherapy and 6
      relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The
      estimated median survival of all patients was 56 months (95% confidence interval,
      27 to infinity) with 11 patients alive; for the Packer protocol, median survival
      was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard
      ratio was 0 (95% confidence interval, 0 to infinity). Toxicity during the Packer
      protocol was moderately severe, with only 1 of 10 patients able to complete all
      therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5
      had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB)
      occurred in 7, neutropenia (<500 microl) in 6, thrombocytopenia (<50,000 microl)
      in 6, nephrotoxicity (>25% decrease by creatinine clearance) in 2, and decreased
      pulmonary function (diffusing capacity for carbon monoxide decrease >40%) in 1.
      On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had
      peripheral neuropathy, and 3 had hearing deficit (>20 dB) or tinnitus. The POG
      and Packer protocols did not have a statistically significant difference in
      relapse-free or overall survival because of the small sample size. The POG
      protocol seemed to have less nonhematologic toxicity. Adults on the Packer
      protocol appeared to have shorter median survival and greater toxicity than did
      children. To know whether adding adjuvant chemotherapy to craniospinal radiation
      in adult therapy increases relapse-free and overall survival, we must await the
      results of a larger randomized controlled clinical trial.

PMID- 11305415
TI  - Interferon-alpha2a and 13-cis-retinoic acid with radiation treatment for high
      grade glioma.
AB  - Interferon-alpha (IFN-alpha) has been safely given concurrently with radiation
      therapy (RT) in treating gliomas. As single agents, both IFN-alpha and cis
      retinoic acid (CRA) have produced objective tumor regressions in patients with
      recurrent gliomas. In vitro, IFN-alpha2a and CRA enhance radiation therapy
      effects on glioblastoma cells more than either agent alone. This trial was
      conducted to determine the clinical effects of IFN-alpha2a and CRA when given
      concurrently with radiation therapy to patients with high-grade glioma. Newly
      diagnosed patients with high-grade glioma received IFN-alpha2a at a dosage of 3
      to 6 million IU s.c. 4 times a day for 3 days per week and 1 mg/kg CRA by mouth 4
      times a day for 5 days per week during the delivery of partial brain radiation
      therapy at 180 cGy x 33 fractions for 5 days per week for a total of 59.4 Gy
      during the 7-week period. Use of the antiepileptic phenytoin was prohibited after
      observing that the combination of IFN-alpha2a, CRA, and phenytoin was associated
      with a high rate of dermatologic toxicity not seen in a previous study with
      concurrent IFN-alpha2a and radiation therapy. Forty patients (26 men and 14
      women) with a median age of 60 (range, 19 to 81 years) were enrolled between
      August 1996 and October 1998. Histopathologic diagnoses were glioblastoma
      multiforme or grade 4 anaplastic astrocytoma in 36 patients, and grade 3
      anaplastic astrocytoma in 4 patients. Only 4 patients (10%) underwent a gross
      total resection of tumor prior to this therapy; 50% were asymptomatic when
      treatment was initiated. The planned 7-week course of concurrent therapy was
      completed by 75% of patients; 30% completed the 16-week course of IFN-alpha and
      CRA alone. At a median follow-up of 36 months, there were 37 deaths, with a
      median overall survival of 9.3 months and a 1-year survival rate of 42%. There
      was no improvement in survival compared with a similar group of 19 patients
      treated with concurrent IFN-alpha2a and radiation therapy in a previous trial. In
      the high-risk group of patients in the present study, concurrent treatment with
      IFN-alpha2a, CRA, and RT was feasible, but was not associated with a better
      outcome compared with a similar patient population treated with radiation therapy
      and IFN-alpha2a, or compared with radiation therapy alone in other trials.

PMID- 11305416
TI  - A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult
      patients with leptomeningeal metastases.
AB  - Leptomeningeal metastases (LMs) are common metastatic complications, occurring in
      at least 5% of patients with disseminated cancer. Cerebrospinal fluid (CSF)
      cytology remains the standard for diagnosis and assessment of treatment response,
      but may be inadequate. Our objective was to compare ventricular and lumbar CSF
      cytology in patients who had cytologically proven LM and were receiving intra-CSF
      chemotherapy. Sixty patients with LM, positive lumbar CSF cytology documented at
      diagnosis, limited extent of CNS disease, and no evidence of CSF flow obstruction
      were treated with a variety of intra-CSF chemotherapies. All patients underwent a
      single simultaneous ventricular and lumbar CSF sampling (mean volume of CSF per
      site examined, 10 ml) to assess response to therapy at either 1 or 2 months after
      treatment initiation. Ventricular CSF cytology was positive in 44 patients (73%),
      35 of whom were also positive by lumbar CSF cytology. Lumbar CSF cytology was
      positive in 45 patients (75%), of which 35 were also positive by ventricular CSF
      cytology. Samples were negative at both ventricular and lumbar sites in 6
      patients (10%). Paired CSF cytologies were discordant in 19 (32%) patients. The
      lumbar cytology was negative in 9, whereas the ventricular cytology was positive
      (lumbar false-negative rate of 17%); the ventricular cytology was negative in 10,
      whereas the lumbar cytology was positive (ventricular false-negative rate of
      20%). In the presence of spinal signs or symptoms of LM, the lumbar CSF cytology
      was more likely to be positive than was the ventricular (odds ratio = 2.86; 95%
      confidence interval, 0.86-9.56). Conversely, in the presence of cranial signs or
      symptoms, the ventricular CSF cytology was more likely to be positive than was
      the lumbar (odds ratio = 2.71; 95% confidence interval, 0.76-9.71). In this
      cohort of patients, whose LM was documented initially by positive lumbar CSF
      cytology, ventricular and lumbar CSF samples obtained during treatment had
      similar false-negative rates, depending on the site of clinical or radiologic
      disease. This suggests that both lumbar and ventricular sites must be sampled
      when assessing treatment response. If clinical or radiographic disease is present
      only at 1 site, then CSF from that site is more likely to be positive than is CSF
      obtained from the more distant site.

PMID- 11305417
TI  - Importance of dose intensity in neuro-oncology clinical trials: summary report of
      the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium.
AB  - Therapeutic options for the treatment of malignant brain tumors have been
      limited, in part, because of the presence of the blood-brain barrier. For this
      reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption
      Consortium, the focus of which was the "Importance of Dose Intensity in Neuro
      Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount
      Hood, Oregon. This meeting, which was supported by the National Cancer Institute,
      the National Institute of Neurological Disorders and Stroke, and the National
      Institute of Deafness and Other Communication Disorders, brought together
      clinicians and basic scientists from across the U.S. to discuss the role of dose
      intensity and enhanced chemotherapy delivery in the treatment of malignant brain
      tumors and to design multicenter clinical trials. Optimizing chemotherapy
      delivery to the CNS is crucial, particularly in view of recent progress
      identifying certain brain tumors as chemosensitive. The discovery that specific
      constellations of genetic alterations can predict which tumors are
      chemoresponsive, and can therefore more accurately predict prognosis, has
      important implications for delivery of intensive, effective chemotherapy regimens
      with acceptable toxicities. This report summarizes the discussions, future
      directions, and key questions regarding dose-intensive treatment of primary CNS
      lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic
      oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The
      promising role of cytoenhancers and chemoprotectants as part of dose-intensive
      regimens for chemosensitive brain tumors and development of improved gene
      therapies for malignant gliomas are discussed.

PMID- 11305418
TI  - Finding the balance.

PMID- 11305419
TI  - A new perspective in the estimation of postmortem interval (PMI) based on
      vitreous.
AB  - The relation between the potassium concentration in the vitreous humor, [K+], and
      the postmortem interval has been studied by several authors. Many formulae are
      available and they are based on a correlation test and linear regression using
      the PMI as the independent variable and [K+] as the dependent variable. The
      estimation of the confidence interval is based on this formulation. However, in
      forensic work, it is necessary to use [K+] as the independent variable to
      estimate the PMI. Although all authors have obtained the PMI by direct use of
      these formulae, it is, nevertheless, an inexact approach, which leads to false
      estimations. What is required is to change the variables, obtaining a new
      equation in which [K+] is considered as the independent variable and the PMI as
      the dependent. The regression line obtained from our data is [K+] = 5.35 + 0.22
      PMI, by changing the variables we get PMI = 2.58[K+] - 9.30. When only
      nonhospital deaths are considered, the results are considerably improved. In this
      case, we get [K+] = 5.60 + 0.17 PMI and, consequently, PMI = 3.92[K+] - 19.04.

PMID- 11305420
TI  - Postmortem assessment of fetal diaphyseal femoral length: validation of a
      radiographic methodology.
AB  - Depending on the general condition of fetal remains, forensic specialists might
      face difficulties concerning age estimation. Reference tables and regression
      equations are helpful devices in this task, although they are generally applied
      for complete fetuses or fetal remains including soft tissues. However, the
      problem of age estimation stays for osseous remains, both for entire bones and
      ossified parts, since most of the reference tables come from ultrasonographic
      measurements, which are not easily reproducible on fetal osseous remains.
      Furthermore, the ultrasonographic measurements contain slight errors in
      comparison to the real anatomical ones. This study describes a radiographic
      protocol and a measurement technique that facilitate and improve bone
      measurements, and therefore, facilitate age estimation, too. A qualitative
      criterion, namely a clear-cut bony endplate, was defined and tested. Its
      reliability (repeatability and reproducibility) turned out to be good, showing
      nonsignificative differences to the threshold of 0.05, with average errors of
      0.26 and 0.44 mm respectively. Moreover, concerning the test of eventual size
      differences between the right and left femurs showed a P value < 0.0001. The test
      of the qualitative criterion was based on the comparison of the radiographic in
      situ femur measurements and the radiographic measurements of the same bones after
      dissection. The results were satisfactory, since an average error of 0.58 mm was
      obtained, which did not give any significant differences to the threshold of
      0.05. It was concluded that this methodology provides an easy and precise new
      measurement tool for forensic practice, and can allow us to establish some
      nonultrasonographic tables, which fit our population.

PMID- 11305421
TI  - Differences in osteon banding between human and nonhuman bone.
AB  - The objective of this paper is to compare patterns of osteon organization in
      human and nonhuman bone. A linear organization of Haversian systems in nonhuman
      bone, where osteons line up in rows, has been reported but has not been
      quantified. The present research provides a quantitative examination of this
      observation through a comparative analysis of the femoral midshaft from human and
      nonhuman bone. Femoral midshaft thin sections from 60 humans were compared to
      femoral midshaft sections from nine sheep and six miniature swine. The presence
      or absence of osteon banding was recorded and, if present, described. Results
      indicate that 2 out of 60 human sections and 5 out of 15 nonhuman sections
      exhibit osteon banding (chi2 = 9.46; p < 0.01). Further, the type of banding
      present in the human and nonhuman samples is easily distinguished, indicating
      that human and nonhuman bone can be distinguished where handing is present in
      this study.

PMID- 11305422
TI  - Examination of variation in sternal rib end morphology relevant to age
      assessment.
AB  - The morphology of the sternal end of the right fourth rib has been proffered as
      an accurate age assessor in skeletonized individuals of both sexes. This
      technique was tested for its applicability on left and right II, III, V-IX. Tests
      were performed between phase scores obtained from right and left ribs; right rib
      IV phase scores and scores obtained from the others in the right rib series; and
      between right rib IV scores and a composite score composed of the average of an
      individual's phase scores (omitting rib IV). Left ribs IV-IX were found not to
      vary significantly from their right counterparts. Although only right rib II was
      found to vary significantly from rib IV, use of the other ribs in the series
      should be undertaken with caution due to questions concerning their statistical
      significance. A composite score is therefore recommended for use instead.

PMID- 11305423
TI  - Macroscopic characteristics of hacking trauma.
AB  - Hacking trauma is often encountered in forensic cases, but little experimental
      research has been conducted that would allow for the recognition of wounds caused
      by specific weapon types. In this paper, we report the results of a hacking
      trauma caused by machete, cleaver, and axe weapons and the characteristics of
      each weapon type on bone. Each weapon type was employed in multiple trials on pig
      (Sus scrofa) bones and then the wounds were examined macroscopically for several
      characteristics that serve to differentiate the weapons.

PMID- 11305424
TI  - Microscopic characteristics of hacking trauma.
AB  - The purpose of this study was to determine if it is possible to associate
      machetes, axes, and cleavers with the microscopic parallel striations they leave
      on the cut surfaces of the bone. Hacking trauma was experimentally inflicted on
      pig bones using machetes, axes, and cleavers. Negative impressions of both the
      cut surfaces of the bone and the weapon blades were analyzed using scanning
      electron microscopy. The results of this investigation indicate that it is
      possible to correlate a class of hacking weapons to trauma inflicted on bone by
      these weapons.

PMID- 11305425
TI  - Processes involved in the development of latent fingerprints using the
      cyanoacrylate fuming method.
AB  - Chemical processes involved in the development of latent fingerprints using the
      cyanoacrylate fuming method have been studied. Two major types of latent prints
      have been investigated-clean and oily prints. Scanning electron microscopy (SEM)
      has been used as a tool for determining the morphology of the polymer developed
      separately on clean and oily prints after cyanoacrylate fuming. A correlation
      between the chemical composition of an aged latent fingerprint, prior to
      development, and the quality of a developed fingerprint has been observed in the
      morphology. The moisture in the print prior to fuming has been found to be more
      important than the moisture in the air during fuming for the development of a
      useful latent print. In addition, the amount of time required to develop a high
      quality latent print has been found to be within 2 min. The cyanoacrylate
      polymerization process is extremely rapid. When heat is used to accelerate the
      fuming process, typically a period of 2 min is required to develop the print. The
      optimum development time depends upon the concentration of cyanoacrylate vapors
      within the enclosure.

PMID- 11305426
TI  - Improved MtDNA sequence analysis of forensic remains using a "mini-primer set"
      amplification strategy.
AB  - Mitochondrial DNA (mtDNA) analysis of highly degraded skeletal remains is often
      used for forensic identification due largely to the high genome copy number per
      cell. Literature from the "ancient DNA" field has shown that highly degraded
      samples contain populations of intact DNA molecules that are severely restricted
      in size (1-4). Hand et al. have demonstrated the targeting and preferential
      amplification of authentic human DNA sequences with small amplicon products of
      150 bp or less (1,2). Given this understanding of ancient DNA preservation and
      amplification, we report an improved approach to forensic mtDNA analysis of
      hypervariable regions 1 and 2 (HV1/HV2) in highly degraded specimens. This "mini
      primer set" (MPS) amplification strategy consists of four overlapping products
      that span each of the HV regions and range from 126 to 170 bp, with an average
      size of 141 bp. For this study, 11 extracts representing a range of sample
      quality were prepared from nonprobative forensic specimens. We demonstrate a
      significant increase in MPS amplification success when compared to testing
      methods using approximately 250 bp amplicons. Further, 16 of 17 independent
      amplifications previously "unreported" due to mixed sequences provided
      potentially reportable sequence data from a single, authentic template with MPS
      testing.

PMID- 11305427
TI  - An environmental survey relating to improvised and emulsion/gel explosives.
AB  - The detection and identification of traces of inorganic ions and sugars can play
      a major role in the forensic investigation of an explosives related incident.
      This survey investigated the background levels of these substances in the general
      environment. Six sampling locations were selected from around the mainland of the
      United Kingdom, representing urban and rural sites. Swab and vacuum samples were
      collected from different locations within each site including motor vehicles,
      private houses, hotels, the exterior of buildings, road surfaces, and street
      signs. Sampling was carried out in summer and winter to investigate changes in
      the levels of the target species due to seasonal factors such as road treatments
      or weather. The samples were extracted with water and analyzed for a range of
      inorganic anions, cations, and sugars using ion chromatography. Most of the
      target anions were found to be common to all locations. Chloride, sulphate,
      nitrate, and phosphate were found to be the most common and the most abundant.
      Chlorate was found at a low level in some external samples. Perchlorate and
      thiocyanate were not detected in any samples. There was a marked increase in the
      quantity of sodium and chloride detected in samples collected during the winter.
      Sodium and calcium were detected in most samples. Potassium and magnesium were
      detected in approximately half of the samples. Ammonium was less common but
      detected at significant levels in wall samples. Glucose, fructose, and sucrose
      were detected in the vacuum samples from the interior surfaces of houses, hotels,
      and cars.

PMID- 11305428
TI  - Compositional analysis for identification of arson accelerants by electron
      ionization Fourier transform ion cyclotron resonance high-resolution mass
      spectrometry.
AB  - Elemental compositions of each of 100 to 500 different constituents (i.e., every
      peak in a mass-to-charge ratio range, 50 < m/z < 300) of lighter fluid, kerosene,
      turpatine, gasoline, diesel fuel, and two brands of mineral spirits (and their
      weathered analogs) make possible direct identification of each accelerant in a
      experimental fire, based on electron ionization 6.0 Tesla Fourier transform ion
      cyclotron resonance (EI FT-ICR) ultrahigh resolution mass spectrometry. Septum
      injection of as little as 500 nL of accelerant into an all-glass heated inlet
      system yields definitive elemental compositions (molecular formulas) based on
      accurate (< +/-1 ppm average error) mass measurement alone. Extraction and EI FT
      ICR mass analysis of fire debris from a controlled burn of a couch with simple
      (lighter fluid) and complex (turpatine) ignitable liquid yielded dozens of
      elemental compositions serving as a unique "fingerprint" for each petroleum
      product, despite the presence of up to 249 additional extracted matrix and
      pyrolysis components. Forty-five of 56 lighter fluid constituents and 126 of 133
      turpatine constituents (not counting 13C-containing species) were identified in
      the debris from a fire staged for each respective accelerant.

PMID- 11305429
TI  - Adhesive tape analysis: establishing the evidential value of specific techniques.
AB  - This study investigated the evidential value of specific methods of analysis for
      packaging tapes and clear adhesive tapes available in Australia. Fifty-eight
      adhesive tapes were analyzed using a wide range of optical, physical, and
      chemical techniques. The results were collated for the purpose of creating an
      Australian database of adhesive tapes, which would be of assistance in criminal
      investigation. Each technique was evaluated for its discriminating power, both
      for comparative purposes and for the identification of adhesive tapes by
      comparing unknown samples with the database. The combined discriminating power of
      the techniques applied is very high. It is possible to individually identify the
      source of an unknown adhesive tape sample in many instances by searching the
      database. It is also possible to form an opinion on the significance of a failure
      to-discriminate result in comparative casework. Further work is still needed to
      expand and update the database, as well as compiling data on the relative market
      share of various products.

PMID- 11305430
TI  - Enhancement of an insufficient dye-formation in the ninhydrin reaction by a
      suitable post treatment process.
AB  - A study of the reaction between ninhydrin and alanine has been carried out taking
      into account that, adhered on the surface of a dry porous medium such as paper, a
      quasi-heterogeneous reaction has to take place. Instead of amino acids released
      from human sweat glands, aqueous solutions of alanine were taken to deliver a
      given amount of amino acid to the sample. The dye density, obtained after using a
      standard development process, could noticeably be increased by setting a drop of
      water on the dye dot, thus indicating that not all the alanine had been used for
      dye formation during the usually applied process. The incomplete reaction can be
      explained by the problem of bringing the reactants into contact with each other
      when both are in the solid phase in the porous surrounding. The temporary
      presence of water allows a reorientation of the insoluble reactants. With
      fingerprints an increase in both the rate of development and the final dye
      density could be obtained when the sample was post treated after the developing
      process with the blank solvent, thus also the background coloration could be
      decreased. The ideas presented in this paper may form the basis for a
      modification of developing processes with ninhydrin in order to increase the
      proportion of amino acids present (in the sample) used in dye formation without
      data loss.

PMID- 11305431
TI  - The application of signal detection theory to decision-making in forensic
      science.
AB  - Signal Detection Theory (SDT) has come to be used in a wide variety of fields
      where noise and imperfect signals present challenges to the task of separating
      hits and correct rejections from misses and false alarms. The application of SDT
      helps illuminate and improve the quality of decision-making in those fields in a
      number of ways. The present article is designed to make SDT more accessible to
      forensic scientists by: (a) explaining what SDT is and how it works, (b)
      explicating the potential usefulness of SDT to forensic science, (c) illustrating
      SDT analysis using forensic science data, and (d) suggesting ways to gain the
      benefits of SDT analyses in the course of carrying out existing programs of
      quality assessment and other research on forensic science examinations.

PMID- 11305432
TI  - A classification of psychological factors leading to violent behavior in
      posttraumatic stress disorder.
AB  - Posttraumatic stress disorder has long been linked to violent behavior. However,
      the exact nature of that association remains poorly characterized due to the
      limitations of knowledge in the area of phenomenology, contextual factors, the
      biology, and the nature of the aggression involved in the disorder. A clear
      understanding of the genesis of violence in posttraumatic stress disorder can be
      helpful to those involved in assessing psychiatric-legal issues relevant to the
      disorder and in its therapeutic management. In this article, we review the
      potential psychological links between posttraumatic stress disorder secondary to
      combat exposure and violent behavior and suggest a tentative classification of
      the main psychological causes of violence in that syndrome.

PMID- 11305433
TI  - Multiple-probe thermography for estimating the postmortem interval: I. Continuous
      monitoring and data analysis of brain, liver, rectal and environmental
      temperatures in 117 forensic cases.
AB  - One hundred seventeen forensic postmortem cases have been studied under
      controlled conditions. In each case, temperatures of the brain, liver, rectum,
      and the environment were monitored over a period beginning shortly after death
      and ending up to 60 h postmortem. The four temperature measurements were recorded
      every 5 to 10 min using the Microwave Thermography System. Rectal and
      environmental temperatures were measured by electrical thermocouples while brain
      and liver temperatures were measured using microwave probes. Data acquisition,
      analogue-to-digital conversion (ADC), and data processing were provided by a
      microcomputer. The ADC technique is described and its problems are discussed. The
      data were then transferred to a mainframe computer for extensive curve-fitting
      and statistical analysis. The microcomputer-based ADC and data logging and
      acquisition were found to be accurate, fast, easy to implement, and useful for
      the field. The postmortem rate of human body cooling was found to be adequately
      represented by triple-exponential equations.

PMID- 11305434
TI  - Multiple-probe thermography for estimating the postmortem interval: II. Practical
      versions of the Triple-Exponential Formulae (TEF) for estimating the time of
      death in the field.
AB  - A simple, reliable, and relatively accurate method for estimating the time since
      death is described. It is based on the Triple-Exponential Formulae (TEF), which
      are devised for the first time in this study. The postmortem cooling rate of the
      brain, liver, and rectum in 117 forensic cases were investigated (Part I). The
      method can be used in the field as a computer program, reference graph, or
      reference chart-ruler. The program is simple and can easily be run by any user.
      There are six reference graphs representing the average brain, liver, and rectal
      cooling curves for naked and covered body groups. The ruler is designed for the
      rectal cooling curves for covered and naked bodies. This method requires one
      temperature measurement of the chosen body site and the environment. The
      postmortem interval is estimated as a probable value +/- a possible range of time
      estimates with a built-in confidence limit.

PMID- 11305435
TI  - Immunostaining by complement C9: a tool for early diagnosis of myocardial
      infarction and application in forensic medicine.
AB  - Before the first 12 hours, diagnosis of early myocardial infarctions is always
      difficult for forensic pathologists. We tested complement C9 expression in 121
      formalin-fixed and paraffin-embedded heart samples by an immunohistochemical
      procedure. The heart specimens were separated into four groups: 33 cases in group
      1 with typical ischemic damages histologically located, 20 cases in group 2 with
      death related to myocardial infarction on the basis of ischemic presentation on
      electrocardiogram but no obvious histological ischemic damage, 35 cases in group
      3 with severe coronary disease without cause of death found at the autopsy, and
      33 cases in group 4 without sign of myocardial infarction and without coronary
      disease. In the first group, all 33 heart samples showed a well-defined C9
      expression in the necrotic areas. The second group in 17 of 20 cases showed
      positive areas for C9 expression. In the other three heart specimens, only few
      stained cells were observed whereas the painful symptoms had begun less than 1 h
      before death. The third group showed C9 immunopositive areas in six of 35 cases,
      few stained cells in 8 cases, and no C9 deposition in the 21 other cases. The
      last group showed no staining area. To avoid nonspecific C9 staining due to
      tissue autolysis, we studied C9 expression during a controlled putrefactive
      process in four cases included in group 1; staining was found only in infarcted
      myocardial areas, and was observed up to ten days. Specificity of C9 expression
      was evaluated to be 100% [89.4 to 100%] and sensitivity to be 85% [62.11 to
      96.79%]. In conclusion, evaluation of immunohistochemical expression of C9
      appears to be a highly sensitive and specific marker of early myocardial
      infarction, useful in forensic medicine if survival is more than 1 h after the
      beginning of myocyte damage.

PMID- 11305436
TI  - Comparison of the rates of hydrolysis of lorazepam-glucuronide, oxazepam
      glucuronide and tamazepam-glucuronide catalyzed by E. coli beta-D-glucuronidase
      using the on-line benzodiazepine screening immunoassay on the Roche/Hitachi 917
      analyzer.
AB  - The catalytic rates of hydrolysis of lorazepam-glucuronide, oxazepam-glucuronide,
      and temazepam-glucuronide when catalyzed by E. Coli. beta-glucuronidase both in
      phosphate buffer and buffered drug-free urine were compared as well as the pH
      dependence of enzyme activity. In 50 mM phosphate buffer pH 6.4, lorazepam
      glucuronide has the highest turnover rate of 3.7 s(-1) with an associated Km of
      about 100 microM, followed by oxazepam-glucuronide, which has a turnover rate of
      2.4 s(-1) with an associated Km of 60 microM. Temazepam-glucuronide has the
      lowest rate of 0.94 s(-1) with an associated Km of 34 microM. In buffered drug
      free urine, a similar trend was observed. In addition, an optimal pH for beta
      glucuronidase was determined to be between 6 and 7 when the enzyme hydrolyzes the
      benzodiazepine conjugates in buffered drug-free urine. Effects of temperature and
      incubation time were also examined. It can be concluded that the electron
      donating or withdrawing of the individual benzodiazepine structure may play an
      important role in the reactivity of the lorazepam-glucuronide, oxazepam
      glucuronide and temazepam-glucuronide catalyzed by beta-glucuronidase. This is
      consistent with other observations made for monosubstituted phenyl-beta
      glucuronides by Wang et al. (1).

PMID- 11305437
TI  - Evaluation of capillary electrophoresis performance through resolution
      measurements.
AB  - The application of resolution measurements to an electrophoretic system can give
      a quantitative analysis of the health of that system. Capillary electrophoresis
      has become a routine method for the analysis of DNA and resolution measurements
      can be used to assess the resulting electropherogram. A number of methods are
      available to evaluate resolution and three methods are detailed in the current
      work. Parameters such as polymer concentration and column length were also
      examined in terms of resolution, and changes therein, if these parameters were
      modified.

PMID- 11305438
TI  - Identifying sex chromosome abnormalities in forensic DNA testing using amelogenin
      and sex chromosome short tandem repeats.
AB  - Forensic DNA laboratories worldwide have begun using multiplexed STR systems to
      decrease analysis time and increase sample throughput. The loci used in these
      systems are basically "nonsense" regions of human DNA. However, due to the
      chromosome on which some of these loci are located, various genetic abnormalities
      can sometimes be detected. This paper will show one such abnormality-
      Klinefelter's Syndrome--and the process used to show the possibility of this
      defect in two undiagnosed males using peak height ratios at the Amelogenin locus,
      and X-Y STRs.

PMID- 11305439
TI  - Cytological detection of spermatozoa: comparison of three staining methods.
AB  - Sperm detection can be an important factor in confirming sexual assault in cases
      of rape. This paper compares three of the most commonly used staining methods
      cited in the scientific literature: Christmas tree. hematoxylin-eosin, and
      alkaline fuchsin. The population studied was composed of 174 consenting women
      seen at the Male Infertility Center in Toulouse. France. The date of their last
      sexual intercourse was accurately known. Alkaline fuchsin did not seem effective
      in detecting spermatozoa in vaginal samples. Compared with hematoxylin-eosin,
      Christmas tree stain appeared to be the most useful test in the first 72 h. Two
      external factors were associated with decreased detection of spermatozoa: time
      since in tercourse and sperm volume.

PMID- 11305440
TI  - An assessment of four solvents for the recovery of 2
      chlorobenzylidenemalononitrile and capsaicins from "CS" and "Pepper" type
      lachrymator sprays, and an examination of their persistence on cotton fabric.
AB  - The rising incidence of assaults involving lachrymator sprays has led to an
      increase in items being submitted to this laboratory for the analysis of the
      associated chemical residues. The following work was undertaken to identify an
      efficient solvent with which to extract the compounds of interest from cotton
      fabric. The persistence and subsequent recovery of such compounds was also
      examined following protracted exposure to wind and rain. Ethyl acetate was
      established as the most efficient solvent of those examined for the extraction of
      2-chlorobenzylidenemalononitrile and a range of capsaicins from "CS Gas" and
      '"Pepper" sprays respectively. Controlled experiments undertaken showed that
      capsaicins were recoverable after 72 h of exposure to the "elements" and 2
      chlorobenzylidenemalononitrile was still recoverable after one week.

PMID- 11305441
TI  - Absorption of ignitable liquids into polyethylene/polyvinylidine dichloride bags.
AB  - Clear plastic bags are often used for the collection, sampling and storage of
      ignitable liquid evidence. They are popular because they are easy to store.
      transport and are inexpensive. Cryovac and Globus brand
      polyethylene/polyvinylidine dichloride bags were tested for suitability in
      storing ignitable liquid evidence. Standards of diesel, kerosene and gasoline
      were placed in the bags and sampled by passive headspace adsorption. The bags
      were then heated to determine if absorbed components of the standards could be
      released upon heating. Recovered extracts were analyzed by GC and GCMS. These
      bags were found to absorb components of diesel, kerosene, and gasoline. and were
      also found to produce interfering by-products that obstruct the chromatographic
      results. Evidence containers need to be tested to ensure that low levels of
      ignitable liquids are not missed.

PMID- 11305442
TI  - Stature estimation from radiographically determined long bone length in a Spanish
      population sample.
AB  - The estimation of stature from of a variety of bones is an important aspect of
      forensic work. In order to obtain reliable results, it is important to have
      comparative data obtained from the same population group as the skeletal remains.
      However, lack of up to date information on the population groups of Southern
      Europe makes the estimation of stature from bones in this area subject to
      possible error. In this study, the stature of 104 healthy adults from Spain was
      measured, and an anteroposterior teleradiograph of the right lower and the right
      upper limb of every subject in the study was made in order to measure the lengths
      of the femur, tibia, fibula, humerus, cubitus and ulna. Pearson's regression
      formulae were obtained for both limbs. In males, we found the femur to be the
      most accurate predictor of stature (R = 0.851), whereas in females best results
      were obtained with the tibia (R = 0.876).

PMID- 11305443
TI  - Survey of stalking at WPI.
AB  - The purpose of this study was to ascertain the amount of stalking taking place on
      the Worcester Polytechnic Institute (WPI) campus in which computers play such a
      huge role in the lives of the students. Our results were then compared with those
      reported in a stalking study done at West Virginia University (WVU). Surprisingly
      (to us), a smaller percentage of both females and males were stalked at WPI. The
      use of the Internet did not play a major role in stalking as we had expected.
      Results reported in a TV news report and a newspaper article indicate, however,
      that much less stalking occurs among the general population than does at WVU and
      WPI.

PMID- 11305444
TI  - Hyperostosis cranii ex vacuo in adults: a consequence of brain atrophy from
      diverse causes.
AB  - Hyperostosis cranii ex vacuo is diffuse thickening of the bones of the cranium
      occurring after successful ventricular shunting in hydrocephalic children,
      presumably as a compensatory phenomenon. We present three adults with severe
      brain atrophy and correspondingly severe skull thickening. In each, the cause of
      cerebral atrophy was well defined, and none had undergone ventricular shunting.
      In two, brain atrophy resulted from different temporally discrete insults
      sustained in adult life, ischemic in one and traumatic in the other. In the third
      case. progressive brain atrophy resulted from a primary neurodegenerative
      disorder, Hallervordan Spatz disease. Our observations suggest that hyperostosis
      cranii ex vacuo is a more general phenomenon than has been previously recognized,
      and point to a relationship between dynamic changes in brain size and skull
      thickness. We suggest that such relationships should be taken into account in
      anthropometric evaluation of the skull.

PMID- 11305445
TI  - The application of minisatellite variant repeat mapping by PCR (MVR-PCR) in a
      paternity case showing false exclusion due to STR mutation.
AB  - A boy and a girl with their mother brought a paternity suit against an alleged
      but deceased father. We tested six conventional genetic markers, the AmpliType
      PM+ DQA1 and twelve STR loci the children and mother together with the alleged
      paternal grandparents. We also DNA typed the bloodstain found later in the
      alleged father's medical record. Only the result at D3S1358 in a nineplex STR
      system excluded the alleged father from parentage of the boy, whereas all markers
      were inclusive for the girl. Accordingly, we performed sequence analysis at
      D3S1358 to confirm the presence of a paternal exclusion or mutation. The sequence
      analysis indicated that the boy's allele 17 could have originated from either of
      the alleged father's allele 16 or 18 by a single-step mutation associated with
      slippage mutation in STR loci. We carried out minisatellite variant repeat
      mapping by PCR (MVR-PCR) at loci D1S8 (MS32) and D7S21 (MS31A) and mapped allele
      haplotypes of all individuals except the deceased alleged father. The MVR-PCR
      analysis showed that the boy has no inconsistency with the relationship between
      the alleged grandparents, and was very effective at increasing the paternity
      index (PI) value. We conclude that there is biological relationship between not
      only the girl but also the boy and the alleged father.

PMID- 11305446
TI  - A shot through the window.
AB  - At issue in this case was whether an unusual window defect seen in two of the
      crime scene photographs was due to a bullet and if so, if that same bullet
      fatally wounded the victim. The window appeared to have been cracked prior to the
      apparent shot through it. A .22 bullet recovered from autopsy, when examined only
      by light microscopy, failed to show associated glass fragments. A previously
      cracked test window was shot a number of times with .22 caliber bullets near the
      cracks in an effort to simulate the window defect seen in the crime scene
      photographs. Several of the defects produced by the test window shots appeared
      similar to the crime scene window defect. The .22 bullet taken from the victim
      and several of the test bullets (collected by a cotton box) were examined by
      scanning electron microscopy/energy dispersive X-ray spectroscopy. The test
      bullets showed glass particles on and embedded in their surfaces. Particles of
      similar size and composition were found embedded in the surface of the bullet
      from the victim. The bullet likely struck the window prior to hitting the victim.
      It was apparent by the morphology of some of the mushroomed test .22 bullets that
      they hit the window crack. These bullets showed that the glass on one side of a
      crack often fails before the other side during the strike. Aggregations of
      powdered glass on many of the mushroomed surfaces of the .22 bullets suggest that
      as the bullet mushrooms during impact on the window surface, the glass in contact
      with the bullet powderizes and coats the mushroomed surface of the bullet with a
      layer of fine glass particles.

PMID- 11305447
TI  - Suicidal ligature strangulation: case report and review of the literature.
AB  - An unusual case of suicidal ligature strangulation is described. The victim is a
      42-year-old white male who devised a very elaborate ligature mechanism comprised
      of thin wire, a plastic tub filled with water, and a combination of other common
      objects to commit suicide while in custody. A brief review of the literature
      follows.

PMID- 11305448
TI  - Fatal cranial injuries caused by an electric angle grinder.
AB  - A case of fatal cranial injuries caused by an angle grinder is reported. The
      scalp lesions were typical of those produced by a cutting disk in a side-slipping
      movement. On the cranial vault were two bony losses of substance, one of which
      was deep enough for intracranial penetration of the disk. Signs of deflection of
      the disk, identical to those found on the scalp, were observed on the external
      bony table. Because of the circumstances in which the victim was discovered, in
      particular the damage to the machine which had a broken handle, and the lack of
      any indication of homicide or suicide, an accident is the most likely hypothesis.

PMID- 11305449
TI  - Sudden death due to primary diffuse leptomeningeal gliomatosis.
AB  - Tumors of the central nervous system are an unusual cause of sudden death. This
      report describes the sudden death of a presumed healthy 28-year-old woman from
      primary diffuse leptomeningeal gliomatosis. She presented to an emergency room
      with headache and vomiting, subsequently became unresponsive and was pronounced
      dead 14 h later. Autopsy revealed a diffuse extensive infiltrate of well
      differentiated astrocytoma in the leptomeninges of the brain and spinal cord
      without an underlying parenchymal tumor. Primary diffuse leptomeningeal
      gliomatosis is a rare tumor that arises within the leptomeninges from small
      neuroglial heterotopic rests that undergo neoplastic transformation. Grossly.
      this tumor can mimic leptomeningeal carcinomatosis, pachymeningitis,
      tuberculosis, sarcoidosis, and fungal infections. However, the histologic
      features of primary diffuse leptomeningeal gliomatosis should allow it to be
      readily distinguished from grossly similar conditions. The mechanism of death in
      this case is most likely tumor obstruction of cerebrospinal fluid outflow
      resulting in the usual complications seen with increased intracranial pressure.
      Although this tumor is aggressive and is associated with a rapidly progressive
      fatal course, it has not been previously associated with sudden death.

PMID- 11305450
TI  - Post-traumatic left ventricular false aneurysm.
AB  - Most false aneurysms of the heart represent contained ventricular free wall
      ruptures after myocardial infarction. Post-traumatic aneurysms also may follow
      penetrating or non-penetrating trauma to the chest. Regardless of the origin of
      the false aneurysm there is a propensity for aneurysm rupture. We report a
      patient who developed a false aneurysm of her left ventricle that developed post
      motor vehicle accident. Her orthopedic problems were the clinical problems
      identified and after a hospital admission of 10 days she was discharged home.
      Four weeks later she died suddenly from anterior left ventricle false aneurysm
      rupture and tamponaide. Patients with significant chest wall trauma should be
      assessed for cardiac pathology prior to discharge. Presentation may be delayed
      and be overshadowed by more evident pathology. Trauma-related aneurysms may cause
      sudden death, and this may occur some later time after the trauma. Attributing
      the cause of death to the trauma, which may be remote, is important for the
      forensic investigator to remember.

PMID- 11305451
TI  - Death due to microvascular occlusion in sickle-cell trait following physical
      exertion.
AB  - The heterozygous condition characterized by the presence of hemoglobin AS (sickle
      cell trait) occurs in approximately 8% of the American black population. Unlike
      the homozygous state (sickle-cell disease), sickle-cell trait is not widely
      recognized as a cause of life-threatening illness or death despite over 30 case
      reports describing fatal or serious complications of exercise in young black
      males with this condition. These reports identify heat stress, dehydration, viral
      illness, and poor physical conditioning as factors which may contribute to
      exertional rhabdomyolysis and sudden death, suggesting multifactorial etiology.
      However, since sickling is known to occur postmortem, it remains controversial as
      to whether the pathogenesis of these exercise related deaths involves
      microvascular obstruction by sickled erythrocytes. We describe three young black
      individuals with no significant past medical history who died following physical
      exertion. In all three cases, postmortem hemoglobin electrophoresis demonstrated
      hemoglobin AS. In none of the cases was the body temperature found to be
      elevated. These cases serve to remind the forensic community that, in the proper
      setting, sickle-cell trait must be viewed as a potentially fatal disorder.

PMID- 11305452
TI  - Suicidal deaths using fireworks.
AB  - The use of commercial explosives is an unusual method of commiting suicide, and
      only a few cases have been described in the medicolegal literature. In this
      paper, two cases of suicide are considered that reflect backgrounds of financial
      problems and psychological illnesses, respectively. Both individuals comitted
      suicide by detonating an explosive (fireworks). In the first case putting the
      explosive on his head and in the second case into his mouth. In both cases the
      cause of death was the destruction of the central nervous system. The following
      cases emphasize the importance of the forensic pathologist in the recognition of
      the scene, as well as the systematical collection of trace evidence of the
      explosion for their subsequent study in the laboratory and their correlation with
      the autopsy findings.

PMID- 11305453
TI  - Carnivore voiding: a taphonomic process with the potential for the deposition of
      forensic evidence.
AB  - Carnivore defecation and regurgitation are taphonomic processes that create
      discrete concentrations of bone pieces and soft tissue fragments of animals that
      have been consumed. Experiments in which baboon carcasses were fed to leopards
      and spotted hyenas demonstrate that primate metapodials and phalanges are well
      represented as readily identifiable specimens in such scat concentrations. Most
      often phalanges are recovered from scat as whole, articulated digit units
      (composed of the proximal through distal phalanges) still covered with ligaments,
      intact skin and finger/toe nails. Considering the very basic similarities between
      baboon and human physiques, the potential applications of these findings to human
      forensic cases are significant. Fingers and toes possess features, including
      fingerprints and, sometimes, distinctive finger and toe rings, useful in the
      identification of human bodies.

PMID- 11305454
TI  - Sudden unexpected death in a patient with splenic sequestration and sickle cell
      beta+-thalassemia syndrome.
AB  - Acute splenic sequestration crisis is a rare disorder that usually occurs in
      children, with sickle cell anemia, who are under the age of five years. A few
      cases have been described in adults with heterozygous sickle cell syndromes.
      Though this entity can be fatal there have been no reported cases associated with
      sudden death. We describe a case of sudden, unexpected death, associated with
      splenic sequestration, in a 29-year-old African-American man with undiagnosed
      sickle cell-beta-thalassemia syndrome.

PMID- 11305455
TI  - Influence of light availability on leaf structure and growth of two Eucalyptus
      globulus ssp. globulus provenances.
AB  - Light availability strongly affects leaf structure of the distinctive ontogenetic
      leaf forms of Eucalyptus globulus Labill. ssp. globulus. Late-maturing plants
      from St. Marys, Tasmania and early maturing plants from Wilsons Promontory,
      Victoria (hereafter referred to as Wilsons Prom.) were grown for 9 months in 100,
      50 or 10% sunlight. Growth, biomass and leaf area were significantly reduced when
      plants were grown in 10% sunlight. Provenance differences were minimal despite
      retention of the juvenile leaf form by the Tasmanian plants throughout the study.
      The time taken for initiation of vegetative phase change by the Wilsons Prom.
      saplings increased with decreasing light availability, but the nodal position of
      change on the main stem remained the same. Both juvenile and adult leaves
      remained horizontal in low light conditions, but became vertical with high
      irradiance. Leaf dimensions changed with ontogenetic development, but were
      unaffected by light availability. Juvenile leaves retained a dorsiventral anatomy
      and adult Wilsons Prom. leaves retained an isobilateral structure despite a
      tenfold difference in light availability. Stomatal density and distribution
      showed ontogenetic and treatment differences. At all irradiances, juvenile leaves
      produced the smallest stomata and adult leaves the largest stomata. Amphistomy
      decreased with decreasing irradiance. Detrended, correspondence analysis
      ordination highlighted the structural changes influenced by ontogenetic
      development and light availability. Adult leaves had characteristics similar to
      the xeromorphic, sun-leaf type found in arid, high-light conditions. Although
      juvenile leaves had characteristics typical of mesomorphic leaves, several
      structural features suggest that these leaves are more sun-adapted than adult
      leaves.

PMID- 11305456
TI  - Genotypic variation in physiological and growth responses of Populus tremuloides
      to elevated atmospheric CO2 concentration.
AB  - Physiological and biomass responses of six genotypes of Populus tremuloides
      Michx., grown in ambient t (357 micromol mol(-1)) or twice ambient (707 micromol
      mol(-1)) CO2 concentration ([CO2]) and in low-N or high-N soils, were studied in
      1995 and 1996 in northern Lower Michigan, USA. There was a significant CO2 x
      genotype interaction in photosynthetic responses. Net CO2 assimilation (A) was
      significantly enhanced by elevated [CO2] for five genotypes in high-N soil and
      for four genotypes in low-N soil. Enhancement of A by elevated [CO2] ranged from
      14 to 68%. Genotypes also differed in their biomass responses to elevated [CO2],
      but biomass responses were poorly correlated with A responses. There was a
      correlation between magnitude of A enhancement by elevated [CO2] and stomatal
      sensitivity to CO2. Genotypes with low stomatal sensitivity to CO2 had a
      significantly higher A at elevated [CO2] than at ambient [CO2], but elevated
      [CO2] did not affect the ratio of intercellular [CO2] to leaf surface [CO2].
      Stomatal conductance and A of different genotypes responded differentially to
      recovery from drought stress. Photosynthetic quantum yield and light compensation
      point were unaffected by elevated [CO2]. We conclude that P. tremuloides
      genotypes will respond differentially to rising atmospheric [CO2], with the
      degree of response dependent on other abiotic factors, such as soil N and water
      availability. The observed genotypic variation in growth could result in altered
      genotypic representation within natural populations and could affect the
      composition and structure of plant communities in a higher [CO2] environment in
      the future.

PMID- 11305457
TI  - Photosynthetic capacity in relation to nitrogen in the canopy of a Quercus robur,
      Fraxinus angustifolia and Tilia cordata flood plain forest.
AB  - We measured gas exchange and various leaf parameters of ash (Fraxinus
      angustifolia Vahl.) and oak (Quercus robur L.) in the high canopy and of lime
      (Tilia cordata Mill.) in the lower canopy of a planted, 120-year-old floodplain
      forest in southern Moravia, Czech Republic. The high-canopy leaves of F.
      angustifolia and Q. robur had nitrogen concentrations on a leaf area basis
      (N(area)) that were twice those of low-canopy leaves of T. cordata. Upper-canopy
      leaves of F. angustifolia had a photosynthetic rate at light saturation (A(max))
      of about 16 micromol CO2 m(-2) s(-1), whereas A(max) of the upper-canopy foliage
      of Q. robur achieved only about two thirds of this value. Contrary to previous
      investigations of photosynthetic performance in monospecific stands, leaves of
      the uppermost branches of T. cordata at 15-m height had the highest A(max) and
      transpiration rate among the species studied. Water-use efficiency (WUE) was low
      in T. cordata at 15-m canopy height, whereas WUE was significantly higher for Q.
      robur leaves at 27-m height than for the other species. Leaves of T. cordata at
      15-m height showed the strongest relationship between A(max) and N(area) (R2 =
      0.90) followed by F. angustifolia (R2 = 0.69). The strong correlation between
      photosynthesis and nitrogen concentration in T. cordata at 15 m, together with
      the steep regression slope for the A(max):N(area) relationship, indicated that
      nitrogen allocation to the photosynthetic apparatus resulted in high nitrogen-use
      efficiency of light-saturated photosynthesis (PNUE). Despite differences in PNUE
      among species, PNUE was fairly constant for leaves sampled from the same canopy
      position, suggesting that single-leaf parameters are matched to optimize PNUE for
      prevailing light conditions. High PNUE in T. cordata at 15 m partially
      compensated for the species' subordinate position in the canopy, and may be an
      important mechanism for its coexistence in highly structured vegetation.

PMID- 11305458
TI  - Oxidase activity in lignifying xylem of a taxonomically diverse range of trees:
      identification of a conifer laccase.
AB  - In a diverse taxonomic range of tree species, including representative species of
      ancient families of angiosperms (Magnolia x soulangiana Soul.-Bod.) and
      gymnosperms (Ginkgo biloba L.), oxidase activity was associated with cell walls
      of developing xylem and was enriched in extracts of cell wall-associated
      glycoproteins. In all species where oxidase activity was detected
      histochemically, it was expressed in cell walls of lignifying, differentiating
      xylem cells and was absent from old wood, cambium and phloem, suggesting that
      oxidases have a conservative role in lignification of tree xylem. An oxidase from
      the developing xylem of Picea sitchensis (Bong) Carr. (Sitka spruce) was
      partially purified by a combination of lectin affinity and immobilized metal ion
      affinity chromatography. A portion of the total oxidase activity had high
      affinity for immobilized zinc ions and this feature allowed it to be separated
      from the bulk of oxidase activity. Two polypeptides that could have been
      responsible for the bound oxidase activity were enriched by this procedure. The
      smaller polypeptide of Mr approximately 73 kDa yielded an N-terminal amino-acid
      sequence that was homologous to laccase-like polyphenol oxidases (E.C. 1.10.3.2)
      from loblolly pine (Pinus taeda L.), poplar (Populus euramericana (Dode) Guinier)
      and Arabidopsis. The larger polypeptide (Mr approximately 77 kDa) yielded an N
      terminal amino-acid sequence that was homologous with a range of plant subtilisin
      like serine proteinases. The roles of oxidase and proteinase activities in
      developing xylem are discussed.

PMID- 11305459
TI  - Variation in branchlet delta13C in relation to branchlet nitrogen concentration
      and growth in 8-year-old hoop pine families (Araucaria cunninghamii) in
      subtropical Australia.
AB  - Carbon isotope composition (delta13C) of branchlet tissue at nine canopy
      positions, and nitrogen concentration (N(mass)) at four canopy positions, were
      assessed in 8-year-old hoop pine (Araucaria cunninghamii Ait. ex D. Don) trees
      from 23 half-sib families, grown in six blocks of a progeny test in southeastern
      Queensland, Australia. There was considerable variation among sampling positions,
      families and blocks in both delta13C and N(mass). The delta13C was positively
      related to N(mass) only for samples from the upper outer crown (P < 0.005).
      Phenotypic correlations existed between tree growth and canopy delta13C.
      Branchlet delta13C of the inner and lower outer crown was positively related (P <
      0.037) to tree height, but delta13C in branchlets of the upper outer crown was
      not related to tree height, or was related negatively (P < 0.045). There were
      significant differences in delta13C between hoop pine families for six canopy
      positions (upper canopy positions as well as lower canopy positions on the
      northern side), with heritabilities greater than 0.40. The significance of these
      findings is discussed in relation to water and light competition within the tree
      canopy of hoop pine.

PMID- 11305460
TI  - Temperature variation and distribution of living cells within tree stems:
      implications for stem respiration modeling and scale-up.
AB  - Few studies have examined variation in respiration rates within trees, and even
      fewer studies have focused on variation caused by within-stem temperature
      differences. In this study, stem temperatures at 40 positions in the stem of one
      30-year-old Norway spruce (Picea abies (L.) Karst.) were measured during 40 days
      between July 1994 and June 1995. The temperature data were used to simulate
      variations in respiration rate within the stem. The simulations assumed that the
      temperature-respiration relationship was constant (Q10 = 2) for all days and all
      stem positions. Total respiration for the whole stem was calculated by
      interpolating the temperature between the thermocouples and integrating the
      respiration rates in three dimensions. Total respiration rate of the stem was
      then compared to respiration rate scaled up from horizontal planes at the
      thermocouple heights (40, 140, 240 and 340 cm) on a surface area and on a sapwood
      volume basis. Simulations were made for three distributions of living cells in
      the stems: one with a constant 5% fraction of living cells, disregarding depth
      into the stem; one with a living cell fraction decreasing linearly with depth
      into the stem; and one with an exponentially decreasing fraction of living cells.
      Mean temperature variation within the stem was 3.7 degrees C, and was more than
      10 degrees C for 8% of the time. The maximum measured temperature difference was
      21.5 degrees C. The corresponding mean variation in respiration was 35% and was
      more than 50% for 24% of the time. Scaling up respiration rates from different
      heights between 40 and 240 cm to the whole stem produced an error of 2 to 58% for
      the whole year. For a single sunny day, the error was between 2 and 72%. Thus,
      within-stem variations in temperature may significantly affect the accuracy of
      scaling respiration data obtained from small samples to whole trees. A careful
      choice of chamber position and basis for scaling is necessary to minimize errors
      from variation in temperature.

PMID- 11305461
TI  - Testing a process-based model of tree seedling growth by manipulating.
AB  - A model was developed that simulated photosynthesis, growth and allocation in
      tree seedlings. The model was parameterized with data from experiments on
      seedlings of sycamore (Acer pseudoplatanus L.), Sitka spruce (Picea sitchensis
      (Bong) Carr.) and young birch trees (Betula pendula Roth.). In these experiments,
      CO2 concentration ([CO2]) and nutrient addition rate were varied. Parameters
      quantifying nutrient uptake, translocation and starch synthesis were fitted,
      based on data from control treatments. Elevated [CO2] and low-nutrient treatments
      were then used to test the predicted response of growth and allocation against
      observations. The model accurately predicted total seedling growth in the
      elevated [CO2] treatments. A response of growth to elevated [CO2] was seen in the
      birch and sycamore experiments, but not in the Sitka spruce, because of
      photosynthetic down-regulation. Predictions of allocation were reasonably
      accurate in the birch and Sitka spruce experiments, but were notably poorer in
      the sycamore experiments, possibly because of differences in sink strength
      between root and shoot. In the birch and sycamore experiments, little change in
      allocation with elevated [CO2] was observed or predicted. This was ascribed to
      the relative values of K(Tc) and K(Tn), the translocation coefficients that
      determine the sensitivity of allocation to carbon and nitrogen uptake rates,
      respectively. Growth and allocation in the low-nutrient treatments were poorly
      predicted by the model. In Sitka spruce, it was suspected that the photosynthetic
      parameters measured in August 1994 had been higher earlier in the season, before
      nutrients became depleted. In sycamore, the discrepancies were thought to relate
      to differences in sink strength between root and shoot that could not be
      described by the model.

PMID- 11305462
TI  - Early detection of human immunodeficiency virus infection using third- and fourth
      generation screening assays.
AB  - Early detection of infection with human immunodeficiency virus (HIV) is critical
      for clinical diagnosis and treatment of patients, as well as for ensuring the
      safety of blood transfusion products. Recently, a number of fourth-generation HIV
      screening assays have been developed that offer increased sensitivity over
      earlier tests by combining detection of anti-HIV antibodies with detection of the
      p24 viral antigen. Previously, six different HIV assays were compared against a
      broad range of 30 seroconversion panels. In the present study, three of the newer
      fourth-generation assays were tested together with three of the third-generation
      HIV antibody-only assays. This extensive analysis highlights (i) the importance
      of p24 antigen detection for early diagnosis, (ii) the improved sensitivity of
      fourth-generation assays over antibody-only tests, and (iii) the superior
      performance of the Vidas Duo assay, which allows reduction of the diagnostic
      window by up to 2 weeks. Finally, the results emphasize the detection limitations
      of the different assays and suggest improvements for future HIV screening assays.

PMID- 11305463
TI  - Detection of Chlamydia pneumoniae DNA in buffy-coat samples of patients with
      abdominal aortic aneurysm.
AB  - Recent studies have suggested that Chlamydia pneumoniae infection is a risk
      factor for abdominal aortic aneurysm. This study explores the presence of
      Chlamydia pneumoniae DNA in buffy-coat samples of control subjects and of
      patients with abdominal aortic aneurysm. The seroepidemiological association
      between abdominal aortic aneurysm and Chlamydia pneumoniae was also investigated.
      Buffy-coat samples and serum specimens were obtained from 88 patients and 88
      control subjects. Detection of Chlamydia pneumoniae DNA in buffy-coat samples and
      measurement of IgG antibodies to Chlamydia pneumoniae in serum specimens were
      performed by polymerase chain reaction and microimmunofluorescence, respectively.
      Chlamydia pneumoniae DNA was detected in buffy-coat samples of 18 (20%) patients
      and 8 (9%) control subjects (adjusted odds ratio 2.9, 95% confidence interval 1
      8.5). IgG antibodies to Chlamydia pneumoniae were detected in 85 (97%) patients
      and 71 (81%) control subjects (adjusted odds ratio 7.2, 95% confidence interval
      1.7-31). The results show an association between abdominal aortic aneurysm and
      either the presence of Chlamydia pneumoniae DNA in buffy-coat samples or IgG
      antibodies to Chlamydia pneumoniae. These findings support the hypothesis that
      previous infection with Chlamydia pneumoniae might be a risk factor for abdominal
      aortic aneurysm.

PMID- 11305464
TI  - Predisposing factors and outcome of Staphylococcus aureus bacteremia in
      neutropenic patients with cancer.
AB  - Staphylococcus aureus caused 30 of 438 (7%) cases of bacteremia in neutropenic
      patients with cancer during a 10-year study period. Acute leukemia as an
      underlying disease and severe oral mucositis were more frequent among patients
      with Staphylococcus aureus bacteremia (57% vs. 33%, P = 0.01, and 32% vs. 12%, P
      = 0.006, respectively) than among the 151 patients who had gram-negative
      bacteremia during the same study period. The most frequent source of
      Staphylococcus aureus bacteremia was the venous catheter (35% vs. 1%; P =
      0.00001). Septic metastases were more frequent in patients with Staphylococcus
      aureus bacteremia (14% vs. 4%, P = 0.03). Attributable mortality was 10% and
      overall mortality 23%. Staphylococcus aureus bacteremia remains a significant
      cause of morbidity and mortality in neutropenic patients with cancer.

PMID- 11305465
TI  - Use of GBS media for rapid detection of group B streptococci in vaginal and
      rectal swabs from women in labor.
AB  - In order to evaluate the differences in efficacy, three methods were used to
      detect group B streptococci (GBS) in women in labor. The recommended method for
      detecting GBS carriage in pregnant women is to culture vaginal and anorectal
      swabs in a selective broth medium and to subculture them onto blood agar. This
      method was compared with the use of GBS agar and GBS broth, both of which produce
      an orange pigment in response to GBS strains. A total of 319 women in labor were
      screened. Among the 638 specimens tested, 134 (21%) were positive in the
      selective Todd-Hewitt broth subcultured onto sheep blood agar, 133 (20.8%) were
      positive on the GBS agar and 126 (19.7%) were positive in the GBS broth.
      Altogether, 89 (27.9%) women in labor were found to be colonized with GBS; 87
      (97.8%) of them were identified as carriers using the Todd-Hewitt broth, 87
      (97.8%) with the GBS agar and 86 (96.6%) with the GBS broth. These results
      indicate that both GBS agar and GBS broth are reliable methods that can be used
      to screen for maternal and neonatal GBS colonization.

PMID- 11305466
TI  - Prospective cohort studies of shigellosis during military field training.
AB  - Epidemiological and clinical features of shigellosis occurring among cohorts of
      Israeli recruits followed-up for 3-6 months during the summer field training of
      years 1993-1997 were studied. The incidence rate of culture-proven shigellosis
      was the highest (78 cases per 1,000 recruits) in 1996 and the lowest (13 cases
      per 1,000 recruits) in 1995. Shigella sonnei (152 isolates) and Shigella flexneri
      (151 isolates) were the most common species. Fifty percent of the patients with
      shigellosis had fever (>37.5 degrees C), compared to only 18% of the subjects
      with other diarrheal diseases (P < 0.001). The duration of illness was longer
      among subjects with shigellosis than among those with other diarrheal diseases (P
      < 0.001). Illness due to Shigella flexneri was more severe than illness caused by
      Shigella sonnei.

PMID- 11305467
TI  - Specificity of a polymerase chain reaction assay of a target sequence on the 31
      kilodalton Brucella antigen DNA used to diagnose human brucellosis.
AB  - The aim of this study was to evaluate the specificity of a polymerase chain
      reaction assay for detecting Brucella DNA using primers specific for the
      amplification of a 223 bp region of the sequence encoding a 31 kDa immunogenic
      Brucella abortus protein (BCSP31). DNA from all Brucella strains, including type,
      reference, vaccine and field strains, were correctly amplified. With the
      exception of Ochrobactrum spp., no other amplification was detected with a broad
      panel of microorganisms serologically or phylogenetically related to Brucella
      spp. This very good degree of specificity, together with its high yield
      demonstrated in previous clinical studies, confirms that this polymerase chain
      reaction assay could be a useful tool for the diagnosis of human brucellosis.

PMID- 11305468
TI  - Candida tropicalis and Penicillium marneffei mixed fungaemia in a patient with
      Waldenstrom's macroglobulinaemia.
AB  - A patient with Waldenstrom's macroglobulinaemia who had previously been treated
      with cladribine presented with septic arthritis caused by Escherichia coli. The
      patient's condition subsequently deteriorated, and he succumbed to pneumonia and
      mixed fungaemia due to Candida tropicalis and Penicillium marneffei. Profound
      lymphopenia coexisted with fungaemia. This is the first reported case of mixed
      Penicillium marneffei and Candida fungaemia and penicilliosis marneffei in a
      patient with Waldenstrom's macroglobulinaemia. Penicilliosis marneffei should be
      considered as a potential complication in patients with markedly impaired cell
      mediated immunity who have travelled to or resided in endemic areas. Patients who
      have undergone therapy with purine nucleoside analogues such as fludarabine and
      cladribine are also at risk.

PMID- 11305469
TI  - Breakthrough Streptococcus pneumoniae meningitis during clarithromycin therapy
      for acute otitis media.

PMID- 11305470
TI  - A severe case of leptospirosis acquired during an iron man contest.

PMID- 11305471
TI  - A case of Trichosporon beigelii endocarditis.

PMID- 11305472
TI  - Oligella ureolytica in blood culture: contaminant or infection?

PMID- 11305473
TI  - Detection of HIV-1 RNA in apparently uninfected children born to mothers infected
      with HIV-1.

PMID- 11305474
TI  - Diagnosis of Streptococcus dysgalactiae subspecies equisimilis (Group C
      streptococci) associated with deep soft tissue infections using fluorescent in
      situ hybridization.

PMID- 11305475
TI  - In vitro susceptibility of Neisseria meningitidis isolates to gemifloxacin and
      ten other antimicrobial agents.

PMID- 11305476
TI  - Efficacy of amphotericin B lipid complex in the treatment of invasive fungal
      infections in immunosuppressed paediatric patients.
AB  - The safety and efficacy of amphotericin B lipid complex (ABLC) were evaluated in
      a retrospective study of 46 paediatric patients with invasive infections. The
      study included a large proportion of patients who were refractory to or
      intolerant of conventional antifungal therapy. The mean age of the children was
      9.7 +/- 4.8 years. Primary underlying conditions included mainly haematopoietic
      stem cell transplantation, leukaemia and lung transplantation. The mean daily
      dose given was 4.11 mg/kg for a mean duration of 38.7 days. At the end of
      therapy, 38 of 46 (83%) patients responded successfully to treatment with ABLC,
      including 18 of 23 (78%) with aspergillosis and 17 of 19 (89%) with candidiasis.
      ABLC was well tolerated, with a low incidence of adverse events. The mean
      creatinine value was 74.5 microl/mol/l at baseline and 78.2 micromol/l at the end
      of therapy. These results support the use of ABLC in the treatment of invasive
      fungal infections in children, including patients who have previously failed, or
      are intolerant of, traditional antifungal regimens.

PMID- 11305477
TI  - Case-control study of risk factors for the development of enterococcal
      bacteremia.
AB  - To determine the risk factors involved in the development of enterococcal
      bacteremia, a prospective, observational, case-control study was carried out over
      18 months. All episodes of enterococcal bacteremia with clinical significance
      detected in adults were included. A control matched by sex, age and
      hospitalization ward (medical, surgical or intensive care unit) was selected
      randomly for each patient with enterococcal bacteremia. Uni- and multivariate
      analyses of the epidemiological characteristics of both groups were performed.
      Etiologic fractions of every risk factor were also determined. One hundred twenty
      two pairs were included. The severity of the chronic underlying diseases was
      similar in both groups. Neutropenia, cirrhosis, organ transplantation,
      intravascular catheter, urinary catheter, nasogastric tube, parenteral nutrition
      and previous administration of cephalosporins and imipenem were the factors
      associated with enterococcal bacteremia in the univariate analysis. The factors
      independently associated with enterococcal bacteremia in the multivariate
      analysis were neutropenia (odds ratio [OR] = 8), urinary catheter (OR = 3) and
      previous administration of cephalosporins (OR = 4) and imipenem (OR = 10). Their
      respective etiologic fractions were 9%, 44%, 11% and 29%. Efforts to reduce the
      occurrence of enterococcal bacteremia should be focused on appropriate use of
      cephalosporins, imipenem and external devices.

PMID- 11305479
TI  - Development of a latex agglutination test for rapid identification of Escherichia
      coli.
AB  - Escherichia coli, one of the most important human pathogens, is usually
      identified by a battery of biochemical tests that require overnight incubation.
      For rapid identification of Escherichia coli, a latex agglutination test (LAT)
      was developed. Rabbits were immunized with cell-surface antigens extracted from
      Escherichia coli CCRC 15481 with 4 M urea, and the affinity-purified antibodies
      were used to coat latex particles for the identification of the bacterium. The
      following gram-negative bacteria were used to evaluate the LAT: Escherichia coli
      (n = 761), Enterobacteriaceae other than Escherichia coli (n = 632), Aeromonas
      spp. (n = 21), Pseudomonas spp. (n = 75), Vibrio spp. (n = 18), and other
      bacteria (n = 64). The LAT had a sensitivity and specificity of 99.2 and 93.3%,
      respectively. If the LAT was used in conjunction with the tests of indole
      production or lactose fermentation, the specificity values for the identification
      of Escherichia coli increased from 93.3 to 98.8 and 98.7%, respectively. If the
      LAT, indole production, and lactose fermentation were used together for the
      identification of Escherichia coli, the sensitivity and specificity were 94 and
      99.7%, respectively. Lactose fermentation could be detected by observing the
      colonies grown on selective media (e.g. MacConkey agar), and indole production
      could be analyzed simply by the spot indole test. Strains producing negative
      reactions (i.e. not identified as Escherichia coli) should be processed by the
      conventional procedures for identification. The present protocol integrating the
      LAT, indole production, and lactose fermentation for the identification of
      Escherichia coli offers considerable savings of time, manpower, and cost.

PMID- 11305478
TI  - Viral excretion in cervicovaginal secretions of HIV-1-infected women receiving
      antiretroviral therapy.
AB  - A longitudinal study was conducted to evaluate the viral shedding present in
      cervicovaginal secretions of HIV-1-seropositive women receiving antiretroviral
      therapy. A total of 128 paired cervicovaginal and blood samples was obtained from
      37 women during a median follow-up period of 21 months. A sensitive, competitive,
      polymerase chain reaction and a reverse transcription polymerase chain reaction
      were used for the simultaneous quantitation of HIV-1 proviral DNA and RNA in
      cervicovaginal cells and cell-free RNA in cervicovaginal secretions, as well as
      HIV-1 RNA in peripheral blood. The cumulative probability of detecting proviral
      DNA in genital secretions was significantly higher over time in women with
      detectable viremia than in women in whom HIV-1 RNA was persistently undetectable
      in plasma (< 50 copies/ml) (P = 0.028 by log-rank test). The presence and amount
      of proviral DNA, cell-associated RNA and cell-free RNA in the cervicovaginal
      secretions were positively correlated with the presence of detectable viremia or
      the number of HIV-1 RNA copies in plasma (Spearman rank correlation, 0.290,
      0.279, and 0.305, respectively; all P < 0.01), but no correlation was found with
      the CD4+ cell count. In addition, vaginal infections were positively correlated
      with the detection of proviral DNA in cervicovaginal secretions (odds ratio,
      2.60; 95% confidence interval, 1.07-5.70). However, the positive correlation
      between the presence and amount of HIV in cervicovaginal secretions and the viral
      load in plasma provides no assurance that HIV shedding does not occur in the
      genital tract of women with undetectable HIV-RNA in plasma.

PMID- 11305480
TI  - Improving in vitro maturation of oocytes in the human taking lessons from
      experiences in animal species.
AB  - One to three per cent of infertile women develop severe ovarian hyperstimulation
      syndrome after superovulation for assisted reproduction treatment (ART). This
      severe complication can be avoided when oocytes are obtained at an immature stage
      (germinal vesicle stage) out of small or medium-sized follicles. This hypothesis
      has been tested in several infertile women, but clinical pregnancies are
      disappointlingly low. This new approach in ART is still at an experimental phase
      and this treatment has still to be improved before routine clinical application.
      Experimental work in animals and humans suggest a beneficial effect in providing
      a short preliminary pretreatment with follicle-stimulating hormone to select for
      a developing cohort of follicles. The aspiration of oocyte cumulus complexes is
      carried out with a short needle applying reduced aspiration pressure. A crucial
      point is to provide the appropriate culture environment for the immature oocytes.
      An optimal cumulus-enclosed human oocyte culture system needs to be defined. The
      composition of the culture medium could be suggested by in vitro work carried out
      in animal models. As developmental competence is established during the latest
      phases of oocyte growth and is dependent on the storage of RNA, a prolonged in
      vitro maturation period (before inducing nuclear maturation) could provide the
      necessary transcriptional and translational changes. The conditions to achieve
      this improved cytoplasmic maturation by prolonging the in vitro culture remain to
      be defined. More objective noninvasive parameters for oocyte maturity are also
      needed to pursue research in this field.

PMID- 11305481
TI  - Protein synthesis during maturation of bovine oocytes, effect of epidermal growth
      factor.
AB  - The objective of this study was to determine whether epidermal growth factor
      (EGF) affected protein synthesis in oocytes during maturation. Initially, the
      effect of EGF on oocyte maturation was examined to ensure that there was a
      beneficial effect of EGF in the protein-free maturation medium used in these
      studies. Results showed that the presence of EGF during maturation significantly
      enhanced cleavage rate and development to the blastocyst stage. Development after
      maturation in the presence of EGF was similar to that seen in medium containing
      serum, luteinizing hormone, follicle-stimulating hormone and estradiol. Protein
      synthesis was examined in immature oocytes and after 16 or 24 h maturation.
      Oocytes from each group were labelled by incubation for 4 h with 35S-methionine,
      the proteins were then separated by two-dimensional sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. Between 400 and 500 proteins could be
      separated using this method and marked changes in protein synthesis was observed
      during maturation. Changes in eight different proteins were observed when protein
      patterns from oocytes matured for 16 h with and without EGF were compared. These
      results suggest that EGF plays a physiological role in oocyte maturation and
      identification of the proteins induced by EGF could be important for improving
      our understanding of oocyte maturation in vitro.

PMID- 11305482
TI  - From co-culture to defined medium: state of the art and practical considerations.
AB  - Embryo culture in domestic and laboratory animals, and also in humans has
      developed significantly during recent decades. It is the aim of this review to
      consider the historical development of different culture systems, with a special
      emphasis on the recent tendency to remove somatic cells and undefined proteins
      from the culture systems for sanitary reasons. In addition to the sanitary
      aspect, developing more standardized culture conditions is useful for diminishing
      variation between laboratories and for studying the needs of the embryo.

PMID- 11305483
TI  - Blastocyst evaluation by means of differential staining: a practical approach.
AB  - Techniques for in vitro production of embryos have been developed world-wide in
      different species, with promising results in human and ruminants. Thousands of
      human IVF-babies have been born during the last 20 years and thousands of in
      vitro-produced calves have been born since the late 1980s. With current methods
      for bovine in vitro fertilization, about 30-40% of in vitro-fertilized bovine
      oocytes develop further to the blastocyst stage and can be used for transfer. A
      proper evaluation of blastocyst quality remains however, an important challenge
      for every researcher involved in embryology and for every clinician who wants to
      select the best embryos for transfer. This review attempts to summarize the
      different methods available for estimation of blastocyst quality with a special
      emphasis upon differential staining.

PMID- 11305484
TI  - In vitro follicle growth: achievements in mammalian species.
AB  - The exact mechanisms regulating in vivo folliculogenesis in mammalians have only
      been partly unravelled. Some processes, such as the initiation of growth of
      primordial follicles are still poorly understood. This increases the difficulty
      to culture follicles in vitro as the primordial follicles will be the ultimate
      starting material for culture. There are important species differences in
      regulation and timing of maturation, which makes it difficult to transpose
      techniques. Only in the mouse model, live pups were born when primordial or early
      preantral follicles were cultured entirely in vitro. Although no systems are as
      yet permitting complete in vitro culture of early follicle stages in large
      animals or humans, parts of folliculogenesis have been successfully reproduced in
      vitro. This review summarizes achievements of the last years in follicle
      culturing starting off at several stages of development. Future applications of
      in vitro follicle culture include fertility preservation for humans, preservation
      of rare animal species and creation of oocyte banks for research.

PMID- 11305485
TI  - Enigmas and variations among mammalian embryos.

PMID- 11305486
TI  - Twenty-four-hour profiles of serum prolactin and luteinizing hormone in
      anoestrous crossbred bitches.
AB  - The dynamics of prolactin (PRL) and luteinizing hormone (LH) secretion in the
      anoestrous bitch is poorly known. Therefore, the objective of this study was to
      characterize the 24 h profiles of serum PRL and LH in crossbred anoestrous
      bitches and to assess whether a relationship exists between the secretory
      patterns of these two hormones. Serum PRL and LH concentrations were measured in
      10 healthy anoestrous crossbred bitches at 145 min intervals for 24 h. During the
      experiment the animals received continuous artificial illumination and remained
      undisturbed except at the time of blood sampling. Serum PRL was measured by a
      homologous enzyme-linked immunosorbent assay, whereas LH and progesterone (P4)
      were determined by radioimmunoassay. The anoestrous state of the bitches was
      assessed by vaginal cytology, vaginoscopy and physical examination. Two groups of
      animals were identified according to their PRL levels: a high PRL group (n = 3,
      mean +/- SEM 12.3 +/- 2.7 ng/ml) and a low PRL group (n = 7, mean +/- SEM: 2.5 +/
      0.9 ng/ml). In the low PRL group, the PRL profiles were flat and did not show
      any significant circadian pattern. Nevertheless, occasional single-point peaks
      were detected in some of the bitches. In the high PRL group the individual PRL
      profiles were variable. To detect the presence of a circadian change of PRL
      concentrations, two different sets of time windows (TW) of sampling were studied.
      The first set was: day [TW1A, samples 1-5 (0900-1840 h)] and night [TW1B, samples
      6-10 (2105-0645 h)]. The second set was chosen after visual inspection of the
      average PRL profiles for both (high and low) groups: [TW2A, samples 3-7 (1350
      2330 h) and TW2B, samples 1-2 and 8-10 (0155-1125 h)]. PRL concentrations were
      not significantly different between day and night. In the high PRL group, but not
      in the low PRL group, average serum PRL was significantly (p < 0.01) higher in
      TW2A than TW2B. In both groups serum LH levels were more homogeneous than PRL
      levels. Neither TW showed circadian changes in LH patterns of secretion (TW1A
      versus TW1B, p < 0.69; TW2A versus TW2B, p < 0.88). On the other hand, bitches in
      the high PRL group showed significantly (p < 0.01) lower serum LH levels than
      those in the low PRL group of animals. Serum PRL concentrations presented a
      significant inverse correlation with LH concentrations (r=-0.21, p < 0.03) and a
      significant positive correlation with P4 concentrations across the study (0.92, p
      < 0.01). It is concluded that in anoestrous crossbred bitches serum PRL is highly
      variable and inversely related to LH. No circadian rhythm of PRL secretion
      appears to exist in most anoestrous bitches.

PMID- 11305487
TI  - Adenocarcinoma of the pancreatic head: can survival be improved?

PMID- 11305489
TI  - Helicobacter pylori status and cell proliferation activity in chronic antral
      gastritis.
AB  - BACKGROUND: Helicobacter pylori is known to cause antral gastritis and multifocal
      atrophic gastritis. In addition to its inflammatory effect, H. pylori has a
      direct effect on gastric mucosa. Increased epithelial proliferation, which may be
      an early biologic change in the development of gastric carcinoma, can be measured
      using silver stain for nuclear organizer regions (AgNOR). AIM: To detect the
      relation between H. pylori colonization and AgNOR index. METHODS: One hundred and
      twenty consecutive antral endoscopic biopsy specimens from patients with
      dyspepsia were examined for H. pylori colonization, polymorphonuclear infiltrate,
      mononuclear infiltrate, germinal center formation, mucus depletion and AgNOR
      index. RESULTS: AgNOR indices were not significantly related to grades of H.
      pylori colonization and chronic and active inflammation. The index increased
      significantly (p=0.03; ANOVA) with increasing mucin depletion. CONCLUSION: H.
      pylori colonization and presence of gastric antral inflammation are not related
      to cell proliferation activity; the latter is associated with mucin depletion.

PMID- 11305488
TI  - Functional protein C and anti-cardiolipin antibody in children with portal vein
      thrombosis.
AB  - BACKGROUND: Portal vein thrombosis (PVT) is a common cause of portal hypertension
      in children from developing countries. Deficiencies of proteins C and S and
      elevated anticardiolipin antibody (aCL) levels have been shown to predispose to
      venous thrombosis. We studied these factors in children with idiopathic PVT.
      METHODS: 19 children with PVT (mean [SD] age 5.7 [2.1] y; 15 boys) were studied;
      all had had variceal bleeding, and had PVT on ultrasonography. Functional protein
      C activity was measured using a clotting assay; if it was normal, a clotting
      assay for functional protein S activity was performed. IgG aCL levels were
      measured in all sera using an in-house standardized solid-phase ELISA. RESULTS:
      Protein C functional activity ranged from 4% to 109%. Eight children had activity
      below 70%, the lower cut-off of the normal range. Protein S assay, done in 10 of
      the 11 children with normal protein C activity levels, was normal (above the cut
      off level of 65% of the normal range). IgG aCL levels were abnormally elevated
      (>mean + 2SD of 16 healthy control children) in nine children; of these, three
      had associated protein C deficiency. Thus, of the 19 children with idiopathic
      PVT, 14 had abnormality in one or more tests. CONCLUSION: A majority of children
      with PVT of unknown etiology have functional protein C deficiency or abnormally
      elevated levels of aCL antibodies.

PMID- 11305490
TI  - Pancreaticoduodenectomy for periampullary carcinoma.
AB  - OBJECTIVES: To assess the morbidity, mortality and 1- and 2-year survival rates,
      and safety of pancreaticoduodenectomy for periampullary (including pancreatic
      head) carcinomas in a non-oncology surgical set-up. METHODS: Records of 45
      patients undergoing pancreaticoduodenectomies for periampullary cancers between
      July 1996 and April 2000 were reviewed. These included ampullary (n=23),
      pancreatic (14) and duodenal (2) adenocarcinomas, lower-end cholangiocarcinoma
      (5), and ampullary carcinoid (1). Thirty-seven patients underwent the Whipple
      procedure and 8 underwent the pylorus-preserving modification. RESULTS: The
      overall mortality rate was 11% and morbidity rate was 46%. Wound infection was
      the most common postoperative complication. The 1- and 2-year survival rates for
      periampullary cancers were 61% and 39% and those for pancreatic cancers were 57%
      and 36%, respectively. CONCLUSION: Pancreaticoduodenectomy for periampullary
      tumors remains a formidable procedure in our set-up. However, it can be performed
      safely with low mortality and morbidity rates.

PMID- 11305491
TI  - Management of esophagorespiratory fistula due to carcinoma esophagus with
      palliative intubation, gastric decompression and transgastric feeding
      jejunostomy.
AB  - BACKGROUND: Carcinoma esophagus with esophagorespiratory fistula has a poor
      prognosis. Water and food intake suffers and pulmonary contamination leads to
      lung infection. Treatment is essentially palliative. METHODS: Thirty-five
      patients with esophagorespiratory fistula secondary to esophageal carcinoma were
      treated with palliative esophageal intubation, gastrostomy and transgastric
      feeding jejunostomy. RESULTS: Esophageal prosthesis could be implanted in 34
      patients. One patient died in the postoperative period. Twenty-nine patients were
      able to swallow saliva without leakage into the lungs. Only four patients were
      able to take full diet orally for any significant length of time. An 18-G needle
      inserted in the gastrostomy Malecot's catheter provided outlet for air in the
      stomach and prevented rise in intragastric pressure and gastroesophageal reflux.
      Transgastric feeding jejunostomy functioned satisfactory. Twenty patients were
      followed up; the average survival was 58 days (range 9-337 days). CONCLUSION:
      Esophageal intubation, gastrostomy and transgastric feeding jejunostomy provide
      satisfactory palliation for patients with esophagorespiratory fistula secondary
      to carcinoma esophagus.

PMID- 11305492
TI  - Risk factors of persistent diarrhea in children below five years of age.
AB  - BACKGROUND/OBJECTIVE: Persistent diarrhea is a known cause of childhood
      mortality, morbidity and malnutrition in developing countries. This study was
      conducted to find out the host and environmental risk factors associated with
      persistent diarrhea in Bangladeshi children below 5 years of age. DESIGN:
      Prospective analytic case-control study. SETTING: Tertiary hospital in Dhaka,
      Bangladesh. METHODS: Fifty children with persistent diarrhea and 50 controls with
      acute diarrhea (matched for age and sex) comprised the study subjects. RESULTS:
      Most of the children (82%) were aged below 2 years. Among the risk factors, Grade
      III malnutrition (p<0.008), irrational antibiotic use during acute diarrheal
      episode (p<0.0000005), use of unsafe drinking water (p<0.004) and lack of
      exclusive breast-feeding up to the first four months of life (p<0.004) were
      significantly associated with persistent diarrhea. Logistic analysis showed
      irrational antibiotic use (p<0.0001) during an episode of acute diarrhea and lack
      of exclusive breast-feeding (p<0.05) during the first four months of life as
      independent risk factors associated with persistent diarrhea. CONCLUSION:
      Improvement of nutritional status, encouraging exclusive breast-feeding during
      the first four months of life, discouraging the irrational use of antibiotic for
      the treatment of acute diarrhea, and provision of safe drinking water may be
      important for the prevention of persistent diarrhea as these have been identified
      as risk factors in Bangladeshi children below five years of age.

PMID- 11305493
TI  - Alterations in duodenal disaccharidases in chronic smokers.
AB  - OBJECTIVE: To assess the effect of smoking on activity of intestinal
      disaccharidases. METHODS: The study was conducted on patients with non-ulcer
      dyspepsia who were smokers (n=20) or non-smokers (n=20). Smokers were classified
      according to smoking index into mild, moderate and heavy smokers. Biopsy
      specimens were taken from the second part of the duodenum at endoscopy and
      examined histologically, and for disaccharidase (lactase, sucrase, maltase and
      trehalase) activities. RESULTS: Mean duration of symptoms was more in smokers
      than in non-smokers. None of the smokers had endoscopic evidence of duodenal
      inflammation. Lactase and trehalase levels were significantly decreased in
      smokers. There was no difference in enzyme levels between mild smokers and non
      smokers. Decreased lactase, maltase and trehalase activities were observed in
      moderate smokers compared to mild smokers. Duration of symptoms had no relation
      to enzyme activities. CONCLUSIONS: Intestinal disaccharidase levels are
      diminished by smoking.

PMID- 11305494
TI  - Primary prophylaxis of variceal bleeding in liver cirrhosis: failure to learn
      from past experience.
AB  - In patients with cirrhosis of liver, variceal bleeding is the most serious
      complication, with a mortality of up to 50%. Primary prophylaxis of variceal
      bleeding with shunt surgery or endoscopic variceal sclerotherapy was attempted
      and then abandoned, as higher rates of complications and mortality were observed.
      Endoscopic variceal ligation is now being recommended for primary prophylaxis in
      some centers, as it has fewer complications than sclerotherapy. But this has been
      done with inadequate evaluation of the cost-effectiveness of variceal ligation.
      Propranolol therapy is also being widely used for a selected group of patients
      (large varices with cherry red spots), despite its several limitations and side
      effects, to reduce frequency of bleeding but without improving survival. Is
      primary prophylaxis of variceal bleeding cost-effective? The cost involved needs
      to be accurately assessed in different countries.

PMID- 11305495
TI  - Pancreaticoduodenectomy for metastatic colonic cancer--report of two cases.
AB  - Benefit of resection of metastatic lesions to the liver and lung from colonic
      cancer is well established. Resection of solitary metastasis or of locally
      recurrent malignancies in the periampullary region has now become the norm, as it
      increases survival. We present our experience with two patients with metastases
      in the periampullary region from previously treated colonic carcinoma who were
      treated with pancreaticoduodenectomy.

PMID- 11305496
TI  - Laparoscopic repair of Morgagni hernia in adult.
AB  - Foramen of Morgagni hernias require surgical treatment; laparoscopic repair is
      another option with lower morbidity. We describe a 35-year-old man with Morgagni
      hernia treated successfully by laparoscopy.

PMID- 11305497
TI  - Gall bladder agenesis, pancreas divisum and undescended testes: a rare
      association.
AB  - Gall bladder agenesis is a rare congenital biliary anomaly that may be associated
      with other biliary and extrabiliary congenital anomalies. We report the
      association of gall bladder agenesis with pancreas divisum and undescended
      testes.

PMID- 11305498
TI  - Laparoscopic resection of liver metastasis using a harmonic scalpel.
AB  - We report successful laparoscopic resection of a solitary liver metastasis from a
      colorectal carcinoma in an obese man, using a harmonic scalpel.

PMID- 11305499
TI  - Intra-abdominal follicular dendritic cell tumor: report of two cases.
AB  - Follicular dendritic cell (FDC) tumor is an uncommon entity described mainly in
      the lymph nodes. We report two men with intra-abdominal FDC tumors--one arising
      from the colon and other presenting as a mesenteric mass. Both patients underwent
      successful surgical excision of the tumor.

PMID- 11305500
TI  - Mantle cell lymphoma presenting as solitary polypoid colonic lesions.
AB  - Mantle cell lymphoma of the intestine is rare, usually presenting as multiple
      small polyps. We report three men with colonic mantle cell lymphoma in the form
      of single large polypoid mass. The clinical picture suggested adenocarcinoma; the
      diagnosis was made at histology and immunohistochemistry of the colectomy
      specimens.

PMID- 11305501
TI  - Lymphocytic interstitial pneumonitis associated with autoimmune hepatitis.
AB  - A 49-year-old woman was diagnosed as autoimmune hepatitis and started on steroids
      and azathioprine. Subsequently, she developed fever; chest radiograph showed
      lower lobe nodular opacities. Bronchoalveolar lavage and transbronchial lung
      biopsy confirmed the diagnosis of lymphocytic interstitial pneumonitis.

PMID- 11305502
TI  - Prevalence of Helicobacter pylori infection by 13C-urea breath test in conference
      delegates.

PMID- 11305503
TI  - Mouth guard for endoscopy custom-made from plastic syringe.

PMID- 11305504
TI  - Acquisition of Helicobacter pylori and reinfection after eradication.

PMID- 11305505
TI  - Blister pack ingestion resulting in esophago-pleural fistula.

PMID- 11305506
TI  - Massive hemorrhage from colonic ulcers in typhoid fever.

PMID- 11305507
TI  - Effect of human immunodeficiency virus on the outcome of hepatitis C virus
      infection.

PMID- 11305508
TI  - The role of nitric oxide on cigarette smoke-induced programmed cell death in the
      gastric mucosa.
AB  - BACKGROUND: This study was designed to investigate the effect of cigarette
      smoking on apoptosis in the gastric mucosa and the role of nitric oxide (NO) in
      the gas phase and extracts in the tar phase in this pathological process.
      METHODS: Male Sprague-Dawley rats and human gastric epithelial cell line AGS were
      used in the study. RESULTS: Cigarette smoking significantly increased apoptotic
      bodies in the rat gastric mucosa. However, neither filtered cigarette smoke, in
      which most of the substances in the tar phase were removed, nor oral
      administration of the two cigarette smoke extracts produced any effect on
      apoptosis. Interestingly, in this experiment pretreatment with a NO donor, the
      chloroform extract (CE) could significantly increase apoptosis. In in vitro
      study, only the CE induced DNA fragmentation, which could be elevated further by
      preincubation with a NO donor. The same extract also elevated inducible nitric
      oxide synthase (iNOS) activity. Inhibition of iNOS by N(G)-nitro-L-arginine
      methylester hydrochloride (L-NAME) partially abolished CE-induced apoptosis.
      CONCLUSIONS: These findings suggested that exogenous and endogenous NO had a
      synergistic effect with substances in the tar phase to induce programmed cell
      death in gastric epithelial cells both in vivo and in vitro.

PMID- 11305509
TI  - Eradication of Helicobacter pylori restores the inhibitory effect of
      cholecystokinin on gastric motility in duodenal ulcer patients.
AB  - BACKGROUND: Increased gastric emptying and defective action of endogenous
      cholecystokinin (CCK), that is known to inhibit this emptying, have been
      implicated in the pathogenesis of duodenal ulcer (DU). The aim of this double
      blind study was to assess whether CCK and somatostatin participate in the
      impairment of gastric motility in active DU patients before and after
      Helicobacter pylori eradication. METHODS: Tests were undertaken in 10 DU patients
      without or with elimination of the action of endogenous CCK using loxiglumide, a
      selective CCK-A receptor antagonist, before and 4 weeks after eradication of H.
      pylori with 1 week triple therapy that resulted in healing of all DUs tested. The
      gastric emptying rate after feeding was determined using the 13C-acetate breath
      test. Before each test, samples of gastric juice were obtained by aspiration
      using a nasogastric tube for determination of somatostatin using specific
      radioimmunoassay. RESULTS: Prior to H. pylori eradication gastric emptying half
      time was 31 +/- 6 min in placebo-treated DU patients and this emptying rate was
      not significantly affected in tests after pretreatment with loxiglumide (10 mg/kg
      i.v.). Following eradication of H. pylori, in tests with placebo gastric emptying
      half-time was significantly longer (48 +/- 9 min) compared to that prior to H.
      pylori eradication. Pretreatment with loxiglumide in H. pylori eradicated DU
      patients significantly enhanced the gastric emptying rate with an emptying half
      time of only 33 +/- 4 min. Eradication of H. pylori resulted in a significant
      increase in somatostatin concentration in gastric juice and loxiglumide
      significantly reduced this luminal somatostatin in H. pylori-eradicated subjects
      compared to values before anti-H. pylori therapy. CONCLUSIONS: 1) H. pylori
      infection in DU patients is accompanied by enhanced gastric emptying and
      reduction in luminal release of somatostatin; 2) the failure of loxiglumide to
      affect gastric emptying in H. pylori-infected DU patients might be attributed, at
      least in part, to the failure of endogenous CCK to control gastric motility due
      to deficient release of somatostatin; and 3) H. pylori-infected patients appear
      to exhibit a deficient somatostatin release by endogenous CCK that can be
      reversed by the eradication of H. pylori indicating that both CCK and
      somatostatin may contribute to normalization of gastric emptying following H.
      pylori eradication in DU patients.

PMID- 11305510
TI  - Helicobacter pylori CagA-positive strains affect oxygen free radicals generation
      by gastric mucosa.
AB  - BACKGROUND: Helicobacter pylori plays a key role in production of reactive oxygen
      metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori
      strains remains to be determined. The aim of this study was to assess ROMs
      production in gastric biopsies of patients infected by H. pylori. Results were
      correlated to CagA status and acute inflammatory infiltration. METHODS: Patients
      undergoing gastroscopy were enrolled. H. pylori infection was assessed by
      histology and 13C urea breath test. CagA status was assessed through serology.
      ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence
      (CLS). Gastric mucosal inflammation was histologically graded and neutrophils
      were individually counted. Macroscopical damage was scored according to a
      modified Lanza score. RESULTS: 40 out of 60 patients evaluated were H. pylori
      (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission
      was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives
      and uninfected. ROMs production showed a significant correlation to neutrophil
      infiltrate in all groups. CONCLUSIONS: Gastric mucosa of patients infected by HP
      CagA-positive strains is characterized by a higher generation of ROMs and by
      greater neutrophil counts than that observed in HP-CagA-negative subjects. Since
      ROMs production is associated with DNA oxidative damage, a long-term stimulation
      by these strains might be relevant in the pathogenesis of gastric malignancies.
      Assessment of CagA status might be useful to discriminate patients in which H.
      pylori eradication is advisable.

PMID- 11305511
TI  - Intestinal adaptation in atrophic rat ileum is accompanied by supersensitivity to
      vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide and
      nitric oxide.
AB  - BACKGROUND: Intestinal inactivity leads to atrophic changes and concomitant
      alterations in the expression of neurotransmitters in the enteric nervous system.
      In atrophic rat ileum neurones expressing vasoactive intestinal peptide (VIP) and
      pituitary adenylate cyclase-activating peptide (PACAP) decrease in number while
      nitric oxide synthase (NOS) expressing neurones increase. Since little is known
      about functional changes accompanying intestinal atrophy the aim of the present
      study was to investigate relaxatory responses to VIP, PACAP-27 and nitric oxide
      (NO) in longitudinal smooth muscle from atrophic rat ileum. METHODS: To create a
      dysfunctional (atrophic) intestine, the distal 10 cm of rat ileum was surgically
      bypassed. In vitro experiments were carried out on longitudinal muscle strips
      from rat ileum having been sham-operated, one week or four weeks bypassed.
      RESULTS: The amplitudes of the relaxatory responses to PACAP-27, VIP and the NO
      donor S-nitroso-N-acetylpenicillamine (SNAP), but not forskolin, were
      significantly increased in the one-week bypassed ileum. In the four-weeks
      bypassed ileum the VIP, PACAP-27, SNAP and forskolin evoked relaxations were of
      the same magnitude as those of the sham-operated. The augmented responses to both
      VIP and PACAP-27 could be blocked by pre-treatment with apamin while N(G)-nitro-L
      arginine methyl ester (L-NAME) and tetrodotoxin were ineffective. In contrast to
      sham-operated and four-weeks bypassed ileum, cross-desensitization between VIP
      and PACAP-27 was noted after one week of bypass. CONCLUSION: Intestinal
      adaptation after bypassing the distal ileum of the rat includes a transient
      supersensitivity of the longitudinal muscle to the NO donor SNAP, VIP and PACAP
      27. These augmented relaxatory responses may contribute to the hypomotility noted
      in inactive intestine.

PMID- 11305512
TI  - Altered expression of the lymphocyte activation markers CD30 and CD27 in patients
      with pouchitis.
AB  - BACKGROUND: The mechanism underlying the development of ileal pouch inflammation
      in ulcerative colitis patients (pouchitis) after restorative proctocolectomy is
      unclear. Persistent systemic T cell activation or expansion of specific memory
      cell populations could predispose certain patients to develop local inflammation
      within the neo-rectum. Therefore, the aim was to study the expression of the
      lymphocyte activation markers CD27, CD30, CD25 and CD69 on the CD45RO+ memory
      cell subset of isolated peripheral blood mononuclear cells (PBMC), soluble CD30
      levels and mucosal CD30 expression in patients with pouchitis and in controls.
      METHODS: Flow cytometry was performed on PBMC isolated from patients with
      pouchitis (n = 9), without pouchitis (n = 10) and normal controls (n = 9). Serum
      CD30 was measured in patients with pouchitis (n = 25), without pouchitis (n = 26)
      and normal controls (n = 20) by ELISA. CD30 expression was quantified in
      pouchitis (n = 15) and normal pouch (n = 15) mucosa using a three-stage
      immunoperoxidase method. RESULTS: Naive CD45RO-CD27+ PBMC were significantly
      decreased in pouchitis (25.6%) compared to normal controls (34.4%), (P = 0.03).
      CD30, CD25 and CD69 subsets did not differ between the groups. Serum CD30 was
      increased in pouchitis patients 58 (1-380) U/ml compared to non-pouchitis 16.5 (1
      290) U/ml, P=0.007, and normal controls 11 (2-80) U/ml, P = 0.0005. In the
      mucosa, the numbers of CD30+ cells were increased in pouchitis compared to non
      inflamed pouches (P = 0.02). CONCLUSIONS: Increased sCD30 in pouchitis is
      associated with elevated mucosal expression. Of the activation markers studied,
      only the circulating naive CD27+ population differed in pouchitis patients
      compared with controls. The observed decrease in this cell type may reflect
      antigen priming and subsequent loss of CD27 implying that antigen driven
      activation of specific T cell subsets may occur in pouchitis.

PMID- 11305513
TI  - Increased levels of specific leukocyte- and platelet-derived substances during
      normal anti-tetanus antibody synthesis in patients with inactive Crohn disease.
AB  - BACKGROUND: Crohn disease is considered a consequence of inappropriate
      upregulation of immune reactions evoked by the intestinal microflora or luminal
      antigens. Since the intestinal mucosa is continuously exposed to tetanus toxoid
      we studied the antibody response to tetanus toxoid booster immunization in
      patients with Crohn disease and the subsequent release of various inflammatory
      mediators and growth factors in blood. METHODS: Ten patients with inactive
      disease and no concurrent medication and 12 age-and gender-matched healthy
      volunteers with anti-tetanus antibody levels less than 0.1 IU/ml were inoculated
      with 1 ml (6 Lf units) of tetanus toxoid vaccine. The anti-tetanus antibody
      levels were determined in serum obtained before inoculation and after 7, 14 and
      28 days, respectively. C-reactive protein (CRP), interleukin-6 (IL-6), tumour
      necrosis factor-alpha (TNF-alpha), histamine, vascular endothelial growth factor
      (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), plasminogen activator
      inhibitor type-1 (PAI-1) and myeloperoxidase (MPO) were determined in serum or
      plasma obtained on the same days. RESULTS: After inoculation anti-tetanus
      antibody levels were equally raised in patients and healthy volunteers. Pre
      inoculation CRP levels were below the upper level of the normal range (<10 mg/l)
      in all inoculated patients/volunteers. No differences in IL-6, TNF-alpha, MPO or
      histamine levels between patients and healthy volunteers were observed. CRP
      levels were within the normal range and IL-6, TNF-alpha, MPO and histamine levels
      were unchanged in patients and volunteers during the study period. The levels of
      VEGF, TIMP-1 and PAI-1 were unchanged in the healthy volunteers during the study
      period, but were significantly (P < 0.05) increased at day 14 in patients with
      Crohn disease. At day 28 the levels had fallen to pre-inoculation levels, apart
      from PAI-1, which was still significantly (P<0.05) increased. CONCLUSIONS: In
      patients with inactive Crohn disease, booster immunization against tetanus toxoid
      seems to result in normal anti-tetanus antibody synthesis, but it may cause
      inappropriate release of certain bioactive substances, which are known to play a
      major role in modulation of the inflammatory response.

PMID- 11305514
TI  - Inhibition of selectin function and leukocyte rolling protects against dextran
      sodium sulfate-induced murine colitis.
AB  - BACKGROUND: The selectin family of adhesion molecules (P-, E- and L-selectin)
      plays an important role in inflammatory reactions by mediating interactions
      between leukocytes and activated endothelial cells. However, a recent study using
      gene-targeted mice has suggested that adhesion molecules (P- and E-selectin and
      ICAM-1) may not be relevant targets in intestinal inflammation. The objective of
      the present study was to re-evaluate the potential role of selectins in
      experimental colitis in wild-type mice using the polysaccharide fucoidan, which
      inhibits the function of P- and L-selectin. METHODS: For this purpose, Balb/c
      mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for 5
      days with and without daily administration of fucoidan (25 mg/kg, i.v.). In
      separate experiments, the effect of fucoidan on leukocyte-endothelium
      interactions was examined by use of intravital microscopy. RESULTS: It was found
      that pretreatment with fucoidan (25 mg/kg/day) reduced mucosal damage and crypt
      destruction in the colon of DSS-treated mice. Moreover, this fucoidan treatment
      markedly reduced the colonic MPO activity in mice exposed to DSS. In vivo
      microscopy revealed that the dose of fucoidan used in the present study abolished
      TNF-alpha-induced venular leukocyte rolling and extravascular recruitment.
      CONCLUSIONS: These results suggest that selectins mediate leukocyte infiltration
      and tissue damage in experimental colitis. Moreover, our data support the concept
      that functional interference with adhesion molecules of the selectin family may
      have a beneficial effect in the treatment of inflammatory bowel disease.

PMID- 11305515
TI  - Transforming growth factor-alpha (TGF-alpha) is not needed for malignant
      transformation in experimental colitis.
AB  - BACKGROUND: Transforming growth factor-alpha (TGF-alpha) is a key mediator of
      colonic mucosal protection and/or repair mechanisms in orally induced acute
      dextran sodium sulphate (DSS) colitis. However, it also has been suggested that
      TGF-alpha may contribute to malignant transformation in the colon. The aim of the
      studies was to determine whether TGF-alpha is needed for malignant transformation
      in orally induced chronic DSS colitis using TGF-alpha deficient mice (wa-1) and
      Balb/c mice, a strain competent in TGF-alpha. METHODS: Chronic colitis was
      induced by oral administration of DSS (5%) for 7 days followed by drinking water
      for 10 days in wa-1 and Balb/c mice (n = 20, per group). In the two subsequent
      cycles (7 days DSS, 10 days water) 3% DSS-water was utilized due to a high
      mortality in the wa-1 group. Mucosal injury severity was assessed histologically
      and graded (three grades). A crypt damage score (CDS) reflecting all three grades
      of mucosal pathology was calculated. Mucosal dysplasia and cancerous lesions were
      noted. RESULTS: Seven per cent of the entire colonic mucosa was completely
      destroyed in wa-1 animals compared to 3% in Balb/c mice (P < 0.05). The CDS was
      10.2 +/- 0.4 and 4.8 +/- 0.3 in wa-1 and Balb/c mice, respectively (P < 0.05).
      Fifteen incidences of mucosal dysplasia were found in the 10 surviving wa-1
      animals and 31 incidences were found in 20 Balb/c animals. In both groups, one
      fully developed adenomatous cancerous lesion was present. CONCLUSIONS: The
      markedly increased severity of mucosal injury in chronic induced DSS colitis in
      TGF-alpha deficient wa-1 mice compared to Balb/c mice further substantiates that
      endogenous TGF-alpha is a pivotal mediator of protection and/or healing
      mechanisms in the colon. The appearance of dysplastic and cancerous lesions in
      TGF-alpha deficient animals suggests that TGF-alpha per se is not essential for
      malignant mucosal cell transformation in colitis.

PMID- 11305516
TI  - Role of N-methyl-N-nitrosourea in the induction of intestinal metaplasia and
      gastric adenocarcinoma in Mongolian gerbils infected with Helicobacter pylori.
AB  - BACKGROUND: Progression from intestinal metaplasia to neoplasia has not been
      demonstrated experimentally. The hypothesis that gastric adenocarcinoma arises
      from intestinal metaplasia was tested in a Mongolian gerbil model of Helicobacter
      pylori (H. pylori) infection. METHODS: One hundred and fourteen specific pathogen
      free gerbils were divided in five groups. A and D: infected with H. pylori and
      administered the carcinogen N-methyl-N-nitrosourea (MNU); C and E: received MNU;
      B: H. pylori, but no MNU. Animals were killed at 41 weeks, stomachs were mapped,
      and the relationship between metaplasia and cancer was assessed. RESULTS:
      Intestinal metaplasia occurred more frequently in the H. pylori-infected, MNU
      treated gerbils than in those receiving H. pylori inoculation only (P < 0.01).
      Carcinomas arose only in H. pylori-infected animals receiving MNU (8 well
      differentiated, 2 poorly differentiated, and 10 signet ring). Intestinal
      metaplasia occurred more frequently in association with intestinal-type
      carcinoma. CONCLUSIONS: Intestinal metaplasia and adenocarcinoma arise in
      stomachs subjected to the same injuries (in this study, H. pylori and MNU). Only
      two intestinal-type carcinomas were contiguous to intestinal metaplasia; all
      other tumors developed most commonly at non-metaplastic sites. This suggests that
      in this animal model H. pylori and MNU induce several phenotypes of gastric
      cancer, but intestinal metaplasia may be a direct precursor only in a subset of
      the intestinal-type tumors.

PMID- 11305517
TI  - A new fecal calprotectin test for colorectal neoplasia. Clinical results and
      comparison with previous method.
AB  - BACKGROUND: Fecal calprotectin is elevated in patients with colorectal cancer
      (CRC). An improved method has been developed. The aim was to evaluate sensitivity
      and specificity for CRC with the new fecal calprotectin method and to compare the
      results with those of the original method. METHODS: The study comprised 453
      subjects including symptomatic CRC patients and CRC high risk subjects with and
      without CRC. Complete colonoscopy was performed. Calprotectin was measured with
      an enzyme linked immunosorbent assay (ELISA) using small (50-100 mg) feces
      samples. RESULTS: Fecal calprotectin levels were significantly elevated in
      symptomatic CRC and in asymptomatic CRC detected in high risk subjects.
      Calprotectin levels were significantly decreased 3 months after cancer removal. A
      cut-off limit of 50 microg/g resulted in a sensitivity of 89% in CRC patients and
      79% in high risk subjects, compared to 89% and 75%, respectively, with the
      original method, using 10 mg/l as cut-off limit. Specificity was improved with
      the new method to 68% and 91% at cut-off of 50 and 150 microg/g, compared to 66%
      and 88%, respectively. Negative predictive value (NPV) was 99% for cut-off of 50
      microg/g in the high risk population. One stool sample was sufficient, but
      measurement of two spots in two stools increased sensitivity to 98% for
      symptomatic and 82% for asymptomatic CRC. CONCLUSION: The new simple method,
      using small samples of feces, had a higher diagnostic accuracy, suggesting that
      it should be preferred to the original one, in screening high risk groups for
      CRC.

PMID- 11305518
TI  - A potential approach for electrochemotherapy against colorectal carcinoma using a
      clinically available alternating current system with bipolar snare in a mouse
      model.
AB  - BACKGROUND: Although electrochemotherapy appears promising for the treatment of
      superficial tumors, its usefulness against internal tumors, such as colorectal
      carcinoma (CRC), has not been well examined. Furthermore, since direct current
      electric pulses have been used for electropermeabilization of tumors in all in
      vivo electrochemotherapy studies, including clinical trials, the usefulness of
      alternating current systems has not been examined at all. In a mouse model it was
      examined whether the alternating current system with a bipolar snare, which has
      been employed already as a clinical endoscopic treatment modality, was useful for
      electrochemotherapy against CRC. METHODS: Murine CRC colon 26 cells were
      implanted subcutaneously into syngeneic BALB/c mice and electrochemotherapy with
      bleomycin (BLM) using the alternating current system was performed against
      established CRC tumors. RESULTS: Electrochemotherapy significantly suppressed the
      growth of established CRC tumors, resulting in significantly prolonged survival
      of animals with CRC. Histological examination revealed that electrochemotherapy
      caused massive necrosis of CRC tumors. Subsequent analysis revealed that the
      delivery of alternating current electric pulses to CRC tumors profoundly
      increased intratumoral amounts of BLM. CONCLUSIONS: Because the alternating
      current system using a bipolar snare has been used widely as an endoscopic
      treatment modality in clinical settings, these results indicate that
      electrochemotherapy using the alternating current system may be a promising
      approach for the treatment of CRC.

PMID- 11305519
TI  - Hemodynamic, metabolic and hormonal responses to oral glibenclamide in patients
      with cirrhosis receiving glucose.
AB  - BACKGROUND: In patients with cirrhosis, glucose may induce splanchnic and renal
      vasodilation. Since the antidiabetic sulfonylurea glibenclamide is known to
      induce splanchnic and renal vasoconstriction in portal hypertensive animals, this
      drug may inhibit glucose-induced hemodynamic responses in patients with
      cirrhosis. The aim of the present study was to investigate, in patients with
      cirrhosis, the short-term effects of glibenclamide on hemodynamic and humoral
      responses to glucose. METHODS: Patients were randomly assigned to receive either
      glibenclamide (5-mg tablet) or a placebo. All patients received an infusion of
      10% glucose (62.5 ml/h for 12 h) that was started at the same time as
      glibenclamide or placebo administration. Studies were performed prior to and 90
      min after glibenclamide or placebo. RESULTS: Glibenclamide (i.e. glibenclamide
      plus glucose) significantly increased plasma insulin concentrations and glycemia
      while placebo (i.e. glucose alone) significantly increased glycemia but did not
      change plasma insulin levels. Glibenclamide did not significantly change the
      hepatic venous pressure gradient while this value was significantly increased
      following glucose alone. Glibenclamide did not significantly change renal blood
      flow and glomerular filtration rate while glucose alone significantly increased
      renal blood flow without affecting the glomerular filtration rate. Glibenclamide
      significantly decreased cardiac index while glucose alone did not change this
      value. CONCLUSIONS: In patients with cirrhosis receiving glucose, glibenclamide
      blunted glucose-induced splanchnic and renal vasodilation. In addition,
      glibenclamide per se induced a decrease in cardiac index. These findings should
      be taken into account when glibenclamide is administered to patients with
      cirrhosis and type 2 diabetes.

PMID- 11305520
TI  - Long-term efficacy of torsemide compared with frusemide in cirrhotic patients
      with ascites.
AB  - BACKGROUND: Torsemide is a new loop diuretic that has shown, in short-term
      studies, to induce a longer and higher diuretic and natriuretic action than
      frusemide. However, torsemide long-term effects and complications have not been
      sufficiently investigated. The aim was to compare the efficacy and safety of
      torsemide versus frusemide in cirrhotic patients with uncomplicated ascites.
      METHODS: Forty-six patients were randomized in two groups to receive torsemide 20
      mg/day (n = 22) or frusemide 40 mg/day (n = 24). Both drugs were administered in
      association with spironolactone 200 mg/day. The initial doses of diuretics were
      increased every 3 days up to 60, 120 and 400 mg/day, respectively, if the body
      weight loss was less than 300 g/day or natriuresis was below 50 mEq/day. RESULTS:
      Torsemide induced a significantly greater diuretic response than frusemide at 24
      h and the maximum diuresis while mean diuresis was similar in both groups.
      Natriuresis was also higher with torsemide but the difference was not
      significant. The body weight loss, the treatment period, the ascites resolution
      and complications were similar in both groups. Diuretic doses were increased in
      two patients treated with torsemide and in nine patients treated with frusemide
      (P < 0.05). CONCLUSIONS: These results show that torsemide is as effective and
      safe as frusemide for long-term treatment of cirrhotic patients with ascites.

PMID- 11305521
TI  - Long-term results after successful extracorporeal gallstone lithotripsy: outcome
      of the first 120 stone-free patients.
AB  - BACKGROUND: Long-term results after successful extracorporeal shock wave
      lithotripsy (ESWL) of symptomatic gallbladder stones are determined by stone and
      complaint recurrence. The long-term outcomes of the first successfully treated
      patients of our Department are presented. METHODS: The first consecutive 120
      patients with symptomatic gallbladder stones who became stone-free after ESWL
      plus oral bile acids in the years 1986 and 1987 were included in this study. They
      were followed up at 1-to 2-year intervals clinically and by ultrasonography until
      April 1998. Recurrence of stones and biliary symptoms and subsequent treatment
      were recorded. The effect of various factors on recurrence was analyzed. RESULTS:
      Median follow-up time was 6.0 years for all patients and 8.8 years for patients
      without recurrence (range, 0-11.2 years for both). Actuarial recurrence
      probability was 1.9%-16.6% per year reaching 60.2% (49.9%, 70.3%) (95% confidence
      interval) after 10 years. Patients with stone recurrence revealed significantly
      more stones before ESWL than patients without recurrence (P < 0.03). Other
      factors were not significantly different. The majority of stone recurrences were
      symptomatic requiring retreatment, mostly cholecystectomy. CONCLUSION: The
      probability of gallbladder stone recurrence after successful ESWL remains high
      during a decade of follow-up. Many patients require repeated nonsurgical
      treatment or cholecystectomy. Thus long-term results are unsatisfactory and ESWL
      should be offered only exceptionally.

PMID- 11305522
TI  - Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation
      against thermodilution and assessment of pharmacological effects of terlipressin
      in portal hypertension.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is a new modality allowing real-time flow
      measurements by means of the Doppler technique. The aim of the study was to
      evaluate azygos blood flow measurements by endoscopic ultrasound. METHODS:
      Measurements of azygos blood flow by EUS and by the thermodilution technique were
      compared in 20 patients with portal hypertension. The ability of EUS flowmetry to
      detect changes in the azygos and portal venous flow after an intravenous dose of
      2 mg of terlipressin was evaluated in 13 of the patients in a double-blind,
      randomized, placebo-controlled, cross-over design. RESULTS: The EUS Doppler and
      thermodilution measurements correlated significantly (R=0.81, P < 0.001). The
      azygos blood flow was found to be 14% higher by the EUS method than by
      thermodilution. The coefficient of variation of the EUS Doppler measurements of
      the azygos blood flow was 14.8%. After administration of terlipressin, the azygos
      blood flow, as measured by EUS Doppler, decreased significantly by 23% from 915
      to 704 ml/min (P = 0.014) and the portal venous flow decreased by 28% from 1170
      to 789 ml/min (P = 0.03). No effects of placebo were detected. CONCLUSIONS: These
      results show that EUS measurement of the azygos blood flow correlate strongly to
      the measurements by the thermodilution technique, and EUS is moreover well
      tolerated by the patients. The method is applicable for monitoring
      pharmacological effects on the superior porto-systemic collateral circulation and
      portal venous flow in patients with portal hypertension.

PMID- 11305524
TI  - Lymph folliculitis in ulcerative colitis.
AB  - Preferential involvement of the appendix has recently been confirmed in
      ulcerative colitis. Since the appendix is an aggregate of lymph follicles, this
      new observation implies a critical role of the lymph follicles, of both the large
      bowel and the appendix, in an etiopathogenesis of ulcerative colitis. This report
      presents two cases of ulcerative colitis in which lymph folliculitis and lymphoid
      hyperplasia were observed. Lymph folliculitis was observed endoscopically in a
      border between an established lesion and an uninvolved area. Case 1, proctitis
      type, relapsing remitting, mild in severity, showed lymph folliculitis in a
      proximal border of an established rectal lesion. Case 2, with left-sided colitis,
      mild in severity, had a skip appendiceal orifice inflammation. Lymph folliculitis
      was observed in the cecum surrounding established appendiceal orifice
      inflammation. In both cases, lymphoid hyperplasia was observed in an uninvolved
      area with clear vascular patterns. These two cases clearly demonstrate the
      involvement of gut lymph follicles in ulcerative colitis. Lymph folliculitis
      and/or lymphoid hyperplasia was proposed to be early lesions in ulcerative
      colitis. In addition, the need for microbiology targeting lymph follicles of the
      large bowel and appendix is stressed in order to disclose the casual microbial
      agents in ulcerative colitis.

PMID- 11305525
TI  - C-reactive protein in cardiovascular risk prediction. Zooming in and zooming out.

PMID- 11305523
TI  - Fas antigen expression on hepatocytes predicts the short- and long-term response
      to interferon therapy in patients with chronic hepatitis C.
AB  - BACKGROUND: Interaction between Fas antigen on hepatocytes and Fas ligand on
      cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV)
      -induced hepatocyte injury. We investigated the usefulness of Fas expression on
      hepatocytes as a predictor of short-and long-term response to interferon (IFN)
      therapy in 72 patients with chronic hepatitis C. METHODS: Ten million units of
      recombinant IFN-alpha2b were administered daily for the first 2 weeks, and three
      times a week for another 22 weeks. The short-term efficacy of IFN therapy was
      evaluated after 12-month follow-up from cessation of treatment. We also examined
      the long-term response to IFN at 56.6 +/- 10.8 (mean +/- s) months after
      termination of IFN therapy in 55 of 72 patients. RESULTS: Univariate analysis
      showed that serum HCV-RNA levels, HCV genotype and Fas expression significantly
      correlated with the short-term efficacy of IFN therapy (P = 0.005, 0.006, and
      0.04, respectively). Fas antigen expression did not correlate with serum HCV-RNA
      levels (P = 0.286), but significantly correlated with HCV genotype (P = 0.003).
      Multivariate analysis indicated that Fas expression and serum HCV-RNA levels were
      independent determinants of the short-term response to IFN therapy. Combined
      together, Fas expression and serum HCV-RNA levels accurately predicted the short
      term response to IFN therapy. On the other hand, in 55 patients who were examined
      the long-term response to IFN, about 60% of Fas-positive patients were HCV-RNA
      negative, whereas 30% of Fas-negative patients were HCV-RNA negative (P = 0.04).
      Among Fas-positive patients, the percentage of those with serum ALT levels
      persistently lower than twice the normal upper limit in long-term study (81.8%;
      9/11) was significantly higher than those in short-term study even among patients
      who failed to show elimination of HCV-RNA (36.4%; 4/11, P = 0.03). CONCLUSION:
      Our results indicate that Fas expression on hepatocytes is a good predictor of
      the short-and long-term response to IFN therapy.

PMID- 11305526
TI  - C-reactive protein: risk assessment in the primary prevention of atherosclerotic
      disease. Has the time come for including it in the risk profile?
AB  - About half of patients presenting with myocardial infarction do not have the
      "classic" risk factors. This has stimulated a search for other factors that may
      be responsible and, when present, may help to predict which patients are at
      greatest risk for myocardial infarction and other cardiovascular events. With
      improved understanding of the pathogenesis of ischemic cardiovascular disease, we
      have gleaned new insights into potential markers of underlying atherosclerosis
      and cardiovascular risk. In recent years, data suggesting that certain markers of
      inflammation--both systemic and local--play a key role in the development and
      progression of atherosclerosis, and in its final clinical complications have
      accumulated. Specifically, elevated levels of one systemic marker of
      inflammation, C-reactive protein (CRP), are associated with an increased risk of
      cardiovascular disease events. Among several markers of systemic inflammation,
      CRP shows the strongest associations with vascular events, and the addition of
      CRP to total cholesterol dramatically improves risk prediction. CRP fulfils most
      of the requirements needed to serve as a new risk factor, but still several
      issues await further confirmation and clarification before this marker can
      ultimately be included in the routine risk profile. Moreover, potentially
      important associations have been established between elevated CRP levels and
      increased efficacy of established therapies, in particular lipid-lowering therapy
      with statins; CRP testing may enable us to tailor expensive cardiovascular
      medication to the individual patient. Such an improved prescription strategy
      might be especially valuable in the primary care setting where the absolute
      cardiovascular risk is considerably lower compared to that in secondary
      prevention.

PMID- 11305527
TI  - Clinical use of C-reactive protein for the prognostic stratification of patients
      with ischemic heart disease.
AB  - C-reactive protein (CRP), the prototypic acute phase reactant and a sensitive
      marker of inflammation, consistently predicts new coronary events, including
      myocardial infarction and death, in patients with ischemic heart disease. The
      data are very consistent with regard to the long-term outcome, but in many
      studies are also significant for in-hospital events. The predictive value of CRP
      is, in the majority of the studies, independent of and additive to that of the
      troponins. Moreover recent data suggest that CRP may be a reliable marker of the
      risk of restenosis after percutaneous coronary interventions and that its levels
      can be modulated by statins. Taken together, all these data suggest that CRP,
      probably with different cut-offs, should be used as a marker of risk and as a
      guide to therapy in patients hospitalized for acute coronary syndromes and in
      outpatients suffering from ischemic heart disease.

PMID- 11305528
TI  - Determination of the habitual low blood level of C-reactive protein in
      individuals.
AB  - In order to use C-reactive protein (CRP) in risk prediction in individuals, it is
      necessary to know how to obtain the habitual level of an individual and hence its
      biological variations: i.e. longitudinal variability within subjects and
      variability between individuals. This paper provides data on biological
      variability that is used to propose a strategy for assessing individual low
      levels of CRP. The longitudinal variability in individuals (intraindividual
      variability) is essential to know, but only reported in a very limited way.
      Additional data were calculated from in-house and requested databases for periods
      of follow-up from 5 days to 1 year. The intraindividual coefficient of variation
      (CVi) was found to be rather similar for several groups and periods and on
      average was approximately 30%. Reported analytical coefficients of variation of
      commercial and in-house methods generally are below 6%, which is well below the
      desired limit of half the CVi. The distribution of CRP in apparently healthy
      individuals is wide and skewed with interquartile values ranging between 150-250%
      of the median and an estimate of the composite coefficient of variation (CVc) of
      approximately 120%. The distribution is equally broad in several other groups
      studied such as type II diabetics and pregnant women. It is concluded that the
      coefficient of variation for the determination of CRP in a single blood sample is
      as high as approximately 30%, but that this is acceptable for the reliable
      positioning of individuals within the distribution of CRP in the group with a CVc
      as high as -120%. CRP can show unexpected outliers (increases) which can
      sometimes be explained by information from a short questionnaire and definitely
      identified by the analysis of a second blood sample after an interval of
      approximately 2 weeks. Similarly, to ascertain high values in a first sample a
      second blood sample can be analyzed. It should be noted that, in view of the
      significant intraindividual variability of CRP, the difference between the first
      and second values may reach 71%. The large intraindividual variability of CRP
      approximating 30% renders it difficult to position an individual reliably in
      smaller categories such as tertiles, quartiles or quintiles of the total
      distribution. It is suggested that it would be most practical to have a goal of a
      single decision level or threshold only. Positioning an individual into two
      groups with equally wide distribution is on the borderline of reliability for one
      blood sample. Multiple blood samplings are required for smaller categories and
      higher threshold levels. The use of a decision limit should further acknowledge
      the limited interclass stability of around r = approximately 0.5 for a single
      blood sample. The above considerations are summarized in a practical working
      scheme. This scheme can serve as a basis for further refinement, discussions and
      development of sampling and decision limits to be selected from medical and
      economical perspectives and tested in practice.

PMID- 11305529
TI  - Medical-economical aspects of high sensitivity C-reactive protein assay for the
      prediction of coronary heart disease. An analysis in Germany and Italy.
AB  - BACKGROUND: Elevated plasma concentrations of C-reactive protein (CRP) are
      associated with increased cardiovascular risk. We studied the cost-effectiveness
      of CRP determination in primary and secondary prevention settings in two European
      countries: Germany and Italy. METHODS: Using a decision analytic model we
      evaluated the costs and consequences of testing or not testing using a high
      sensitivity (hs)-CRP assay. In a primary prevention model we analyzed a
      hypothetical cohort of 300000 apparently healthy men divided into three age
      groups (35-44, 45-54 and 55-64 years). Individuals with CRP levels > 3 mg/l were
      administered either aspirin or statins according to lipid levels. The cohort was
      followed for 5 years. In the secondary prevention model hs-CRP testing was
      evaluated in a cohort of 10000 patients with total cholesterol levels < 4.52
      mmol/l and a history of myocardial infarction or unstable angina. The two
      strategies tested were: 1) administer pravastatin only to those with high CRP
      values, and 2) treat all patients. The analysis was performed from the societal
      perspective. Event rates were obtained from epidemiological studies and clinical
      trials. RESULTS: In the primary prevention model, strategies including testing
      showed, for men aged 45 years and older, cost-effectiveness ratios between each
      life year saved (LYS) and cost savings in Germany equal to 10217euro and between
      each LYS and savings in Italy equal to 16950euro In the age group 35-44 years,
      therapy with aspirin showed cost-effectiveness ratios of 5318euro and 11203euro
      per LYS in Germany and in Italy respectively. The widespread use of statins
      showed an unfavorable cost-effectiveness profile: 44630euro per LYS in Germany
      and 36270euro per LYS in Italy. In the secondary prevention model, hs-testing for
      CRP can reduce the cost-effectiveness of pravastatin from 16400 to 6830euro per
      quality adjusted life year gained. Sensitivity analysis performed on the
      variables test price and costs of cardiovascular events resulted in minimal
      changes of the cost-effectiveness ratios. CONCLUSIONS: Both in the primary and
      the secondary prevention settings, hs-testing for CRP can better target
      individuals at higher risk, thus improving outcomes and resulting in a more cost
      effective strategy.

PMID- 11305530
TI  - Determinants of C-reactive protein concentration in blood.
AB  - C-reactive protein (CRP) is a very strong acute phase protein. During the acute
      phase of disease the CRP concentration can increase up to a thousand-fold.
      However, a higher CRP concentration is also observed during chronic stages of
      disease, for example in subjects with chronic bronchitis, periodontal disease or
      subjects with increased titers of Helicobacter pylori or Chlamydia pneumoniae.
      The concentration of CRP is also reported to be associated with age, sex, race,
      smoking, obesity, consumption of coffee and alcohol, stress, physical training,
      lipid levels, and blood pressure. Statins decrease the CRP concentration whereas
      estrogen increases it. With regard to most other drugs no consistent relationship
      has been reported.

PMID- 11305531
TI  - C-reactive protein and atherothrombosis.
AB  - Circulating concentrations of C-reactive protein (CRP), the classical acute phase
      protein and sensitive systemic marker of inflammation, significantly predict
      atherothrombotic events and outcome after acute myocardial infarction,
      demonstrating the key role of inflammation in atherosclerosis and its
      complications. The binding specificity of CRP for low density lipoproteins, for
      modified low density lipoproteins, and for damaged and dead cells, coupled with
      the capacity of bound CRP to activate complement, and with the presence of CRP in
      atheroma and acute myocardial infarction lesions, all suggest a possible
      pathogenetic role of CRP. Development of drugs to block binding of CRP to its
      various ligands in vivo will enable this hypothesis to be tested.

PMID- 11305532
TI  - Neural control of the cardiovascular system during exercise.
AB  - The objective of this review was to give an overview on the current knowledge on
      the neural mechanisms of cardiovascular regulation during exercise. Evidence
      derived mainly from human studies which supports the contribution of the
      different control mechanisms, namely the central command, the reflex drive from
      active muscles and the arterial baroreflex, with the attendant modifications in
      autonomic nervous system activity, in determining the cardiovascular responses to
      exercise are discussed, along with some controversial issues and evolving
      concepts in exercise physiology. In particular, data that show how the various
      neural mechanisms involved in cardiovascular regulation during exercise are
      differently modulated by factors related to the muscular activity being
      performed, such as the type and intensity of exercise and the size of the active
      muscle masses are presented, stressing the plasticity of the neural network.
      Finally, clinical implications pertaining to neural cardiovascular regulation and
      exercise are advanced.

PMID- 11305533
TI  - Incidence and predictors of sudden cardiac death during long-term follow-up in
      patients with dilated cardiomyopathy on optimal medical therapy.
AB  - BACKGROUND: In spite of a total mortality reduction in recent years, sudden
      cardiac death (SD) remains a major problem in patients with idiopathic dilated
      cardiomyopathy (IDC) and its occurrence is often unpredictable. Furthermore, the
      risk of SD may change during follow-up because of the natural history of the
      disease and the effects of therapeutic interventions. In our study, we evaluated
      the modifications of the risk of SD during follow-up in a cohort of patients with
      IDC and analyzed the variables predicting SD not only at enrolment but also at
      the last examination during optimal medical treatment. METHODS: Since 1978, 343
      consecutive patients with IDC were enrolled in the Heart Muscle Disease Registry
      of Trieste (Italy) and submitted to complete invasive and non-invasive study.
      Patients were re-evaluated usually at intervals of 12 months. RESULTS: After a
      mean of 68+/-45 months, 125 events (death, heart transplantation or aborted SD)
      had occurred. The cumulative risk after 5 years was 30%, while after 10 years it
      almost doubled (54%). During the first 3 months after enrolment, the incidence of
      SD was high (3%). A plateau, lasting about 3.5 years, followed. A slow but
      progressive rise in the risk of mortality then occurred (6% at 5 years, 18% at 10
      years). No variables evaluated at enrolment were associated with SD at
      multivariate analysis. On the other hand, the end-diastolic left ventricular
      diameter (> or = 38 mm/m2) and ejection fraction (< or = 0.30) were predictive of
      SD if evaluated within 1 year before the event. Beta-blocker treatment was
      associated with a non-significant reduction of risk. CONCLUSIONS: In patients
      with IDC the incidence of SD progressively increased during long-term follow-up,
      especially in those with persistent severe left ventricular dilation and
      dysfunction who were not on beta-blocker treatment. Serial clinical evaluation
      may help to select patients at higher risk for SD.

PMID- 11305534
TI  - Cardiac contusion in blunt chest trauma: a combined study of transesophageal
      echocardiography and cardiac troponin I determination.
AB  - BACKGROUND: The role of cardiac troponin I (cTnI) is well established in acute
      myocardial ischemia. However, its role in myocardial contusion remains to be
      clarified. Since transesophageal echocardiography (TEE) appears, at present, to
      be the best method for the diagnosis of myocardial contusion, the aim of this
      study was to measure the concentration of cTnI in patients with blunt chest
      trauma studied using TEE. METHODS: Thirty-two patients (27 males, 5 females, mean
      age 44+/-20 years), admitted to the Trauma Center of our Institution with
      clinical and/or radiological signs of acute blunt chest trauma, underwent biplane
      TEE within 24 hours of injury; serial blood samples were taken to measure cTnI
      levels (normal values < 0.4 ng/ml), using fluorimetric enzyme immunoassay.
      RESULTS: Abnormal levels of cTnI were found in 17 patients (53%): 7 patients had
      levels of cTnI between 0.4 and 1 ng/ml, whereas 10 patients had levels > 1 ng/ml.
      Segmental wall motion abnormalities consistent with myocardial contusion could be
      identified by echocardiography in 6/10 patients with cTnI levels > 1 ng/ml (60%)
      but in no patients with normal cTnI levels or with titers between 0.4 and 1
      ng/ml; mean cTnI levels showed a significant difference between the two groups of
      patients with and without echocardiographic signs of myocardial contusion (2.6+/
      1.6 vs 0.6+/-1.4 ng/ml, p < 0.001). CONCLUSIONS: Abnormal titers of cTnI
      suggesting myocardial contusion may be found in more than half of patients with
      blunt chest trauma; however, myocardial injury can be detected by TEE only for
      cTnI levels > 1 ng/ml; cTnI concentrations ranging between 0.4 and 1 ng/ml might
      be indicative of myocardial microlesions, not detectable by echocardiography,
      even if TEE is used; cTnI assay could therefore be suggested as a screening test
      before performing TEE after blunt chest trauma.

PMID- 11305535
TI  - A rare form of interrupted aortic arch.
AB  - We report the case of a newborn with DiGeorge syndrome and aortic atresia
      associated with a complex anomaly of the aortic arch, interpreted as interrupted
      aortic arch type C, a persistent right ventral aorta and an aberrant right
      innominate artery. At 8 months the child underwent Norwood palliation with
      interposition of an 8 mm PTFE tube between the pulmonary trunk and the descending
      aorta and of a 3.5 mm shunt between the junction of the right ventral aorta to
      the left carotid artery and the right pulmonary artery. At 11 months he had
      substitution of the PTFE tube and bidirectional cavopulmonary anastomosis; he is
      now waiting for biventricular correction.

PMID- 11305536
TI  - Amiodarone-induced torsade de pointes in a child with dilated cardiomyopathy.
AB  - Amiodarone has a high incidence of side effects, but few pro-arrhythmic effects.
      We report a case of amiodarone-induced torsade de pointes in a child aged 10
      years. The patient had severe dilated cardiomyopathy, and even though he was
      treated with low oral doses of amiodarone, without dosage increments and
      electrolyte imbalance, he developed torsade de pointes at nights, after T-wave
      modification and increases of the corrected QT interval (QTc, 20%), QT dispersion
      (QTd, 175%) and QTcd (116%). The arrhythmic events were preceded by sinus
      bradycardia at Holter monitoring. Amiodarone therapy was discontinued.
      Intravenous magnesium administration was not effective in the suppression of
      torsade de pointes. High-rate atrial pacing prevented recurrences of the
      arrhythmias and reduced the QTc interval by 20%, QTd by 50%, and QTcd by 70%; QTd
      and QTcd returned below normal limits. This case underscores the need of careful
      electrocardiographic monitoring during amiodarone therapy.

PMID- 11305537
TI  - Rupture of an aneurysm of the noncoronary sinus of valsalva into the right
      atrium: the "wind sock" echocardiographic appearance.

PMID- 11305538
TI  - Inadequate reducing systems in pre-eclampsia: a complementary role for vitamins C
      and E with thioredoxin-related activities.

PMID- 11305539
TI  - Cardiovascular function in pregnancy: effects of posture.
AB  - OBJECTIVE: To evaluate the cardiovascular response to active postural changes in
      pregnancy. DESIGN: Prospective study. SETTING: Outpatient Clinic, Fetal Maternity
      Unit. PARTICIPANTS: Sixteen healthy women referred prior to pregnancy. METHODS:
      Heart rate, arterial pressure, echocardiographic end-diastolic and end-systolic
      left ventricular volumes (Teichholz' s formula) were measured in the three months
      before pregnancy, at the end of the first and second trimester, at mid third
      trimester, and six months after delivery in the supine and standing position, in
      thirteen women (mean age 33, range 25-38 years). RESULTS: Cardiac output (supine
      position) significantly increased (28%): it reached its maximum at the second
      trimester, remained steadily elevated in the mid third trimester, and returned to
      baseline after delivery. Cardiac output increased during pregnancy also in the
      active orthostatic position, the percentage increase being greater (70%) since
      the standing pre-conception value was lower. The postural stress induced similar
      changes in heart rate, arterial pressure and left ventricular ejection fraction
      before, during and after pregnancy. However, the reduction in cardiac output
      associated with early standing attenuated significantly at the second trimester
      and it was absent at mid third trimester (F = 3.13, P = 0.021). This was due to
      the interplay between the significantly lesser increase in systemic vascular
      resistance, occurring since the first trimester, and the significantly lesser
      decrease in left ventricular end-diastolic volume which was observed in the mid
      third trimester. CONCLUSION: These data indicate that the elevated cardiac output
      is adequately maintained in pregnancy during the postural challenge, due to
      optimisation of the responses of preload and afterload.

PMID- 11305540
TI  - Assessment of cerebral hemodynamics during roll over test in healthy pregnant
      women and those with pre-eclampsia.
AB  - OBJECTIVE: To compare cerebral autoregulatory responses obtained during roll over
      tests in healthy pregnant women and those with pre-eclampsia in order to assess
      the middle cerebral artery velocity changes in relation to the roll over test in
      normotensive and pre-eclamptic women. PARTICIPANTS: Twenty-two healthy pregnant
      women and 26 with pre-eclampsia underwent transcranial Doppler measurements of
      the middle cerebral artery. METHODS: Systolic, mean and diastolic blood flow
      velocities and mean arterial blood pressures were recorded in the left lateral
      position and five minutes after turning to the supine position. Absolute values
      of mean blood flow velocities, mean arterial blood pressure values and calculated
      cerebral blood flow indices as well as cerebrovascular resistance area products
      were compared at different positions among the groups. RESULTS: Mean arterial
      blood pressure increased in both groups while turning from the left lateral to
      the supine position. In women with pre-eclampsia both mean arterial blood
      pressure and absolute values of mean blood flow velocity values were higher in
      both positions, compared with healthy pregnant women. In both groups, changing
      the position resulted in a decrease of absolute values of mean blood flow
      velocities. Calculated cerebral blood flow indices did not change, while
      cerebrovascular resistance area products increased significantly in the groups
      during roll over testing. In women with pre-eclampsia, the increase of
      cerebrovascular resistance area products was more pronounced as compared with
      healthy pregnant women. CONCLUSIONS: In women with pre-eclampsia roll over test
      results in an increase of the mean arterial blood pressure, which is accompanied
      by a decreased mean blood flow velocity in the middle cerebral artery. Further
      studies are needed to clarify the pathophysiological background of cerebral
      haemodynamic changes in pre-eclampsia.

PMID- 11305541
TI  - Circulatory responses to maternal hyperoxaemia and hypoxaemia assessed non
      invasively in fetal sheep at 0.3-0.5 gestation in acute experiments.
AB  - OBJECTIVES: To determine fetal haemodynamic responses to hyperoxaemia and
      hypoxaemia in early pregnancy. DESIGN: Repeated measurements in acute
      experiments. SETTING: Experimental physiology laboratory. METHODS: Non-invasive
      Doppler ultrasound of the umbilical vein, ductus venosus, umbilical and common
      carotid arteries of 12 fetal lambs (0.27-0.56 gestation) during maternal
      hyperoxaemia and hypoxaemia under ketamine anaesthesia. The effect of gestational
      age, hyperoxaemia, and hypoxaemia were assessed based on analysis of variance for
      dependent measurements and P < or = 0.05 was considered significant. Differences
      between groups were considered significant if the 95% confidence interval did not
      include zero. RESULTS: Gestational age had a significant effect on the blood
      velocity in the umbilical vein and ductus venosus. There were no circulatory
      changes during hyperoxaemia, but a simultaneous increase of pCO2 was an important
      confounder. However, hypoxaemia caused significantly reduced heart rate, reduced
      maximum and weighted mean blood velocity, and augmented pulsation in the
      umbilical vein. Hypoxaemia also caused reduced velocities in the ductus venosus
      (peak velocity during systole and minimum during diastole, and time-averaged
      velocity) and augmented pulsation of the flow velocity. Additionally, the
      pulsatility of blood flow increased in the umbilical artery and was reduced in
      the common carotid artery. CONCLUSIONS: Maternal hypoxaemia in early pregnancy
      causes similar fetal circulatory responses to those in late pregnancy:
      bradycardia, reduced venous flow velocities, augmented pulsatility in veins and a
      redistributional flow velocity pattern of the umbilical and common carotid
      arteries.

PMID- 11305542
TI  - Hepatitis C virus among high and low risk pregnant women in Dundee: unlinked
      anonymous testing.
AB  - OBJECTIVE: To determine the prevalence of the hepatitis C virus among pregnant
      women, to gauge the non-injecting, particularly sexual, risk of them being
      hepatitis C virus infected and to assess the potential impact of selective
      antenatal screening. POPULATION: Antenatal clinic attenders and women undergoing
      termination of pregnancy in 1997. SETTING: Ninewells Hospital, Dundee. DESIGN:
      Unlinked anonymous hepatitis C virus antibody testing of residual sera from
      specimens sent to the virus laboratory for routine serological testing. The
      results were linked to non-identifying risk information. RESULTS: Overall anti
      hepatitis C virus prevalence was 0.6% (23/3,548). Prevalences among injecting
      drug users, non-injectors who had a sexual partner who injected, and those with
      neither risk respectively were 41% (7/17), 15% (5/33) and 0.3% (11/3,498).
      Relative risks for being an injector and a sexual partner of an injector
      respectively were 131 (95% CI 58-297) and 48 (95% CI 5-32). It is estimated that
      one of the 18 antenatal clinic attenders gave birth to an infected child.
      CONCLUSION: Findings suggest that non-injecting partners of injectors may be at
      considerable risk of acquiring hepatitis C virus sexually. Efforts to promote the
      use of condoms among injectors and their sexual partners should be increased.
      Selective anti-hepatitis C virus screening of women who reported high risk
      behaviour would have failed to detect half the cases. Research to gauge the views
      of women of childbearing age on anti-hepatitis C virus testing is required.

PMID- 11305543
TI  - Effects of mode of delivery and infant feeding on the risk of mother-to-child
      transmission of hepatitis C virus. European Paediatric Hepatitis C Virus Network.
AB  - OBJECTIVE: To investigate the effects of mode of delivery and infant feeding on
      the risk of mother-to-child transmission of hepatitis C virus. DESIGN: Pooled
      retrospective analysis of prospectively collected data. SAMPLE: Data on hepatitis
      C virus seropositive mothers and their children identified around delivery were
      sent from 24 centres of the European Paediatric Hepatitis C Virus Network. MAIN
      OUTCOME MEASURES: Hepatitis C virus infection status of children born to
      hepatitis C virus infected women. RESULTS: A total of 1,474 hepatitis C virus
      infected women were identified, of whom 503 (35%) were co-infected with HIV. Co
      infected women were more than twice as likely to transmit hepatitis C virus to
      their children than women with hepatitis C virus infection alone. Overall 9.2%
      (136/1,474) of children were hepatitis C virus infected. Among the women with
      hepatitis C virus infection-only, multivariate analyses did not show a
      significant effect of mode of delivery and breastfeeding: caesarean section vs
      vaginal delivery OR = 1.17, P = 0.66; breastfed versus non-breastfed OR = 1.07, P
      = 0.83. However, HIV co-infected women delivered by caesarean section were 60%
      less likely to have an infected child than those delivered vaginally (OR = 0.36,
      P = 0.01) and those who breastfed were about four times more likely to infect
      their children than those who did not (OR = 6.41, P = 0.03). HIV infected
      children were three to four times more likely also to be hepatitis C virus
      infected than children without HIV infection (crude OR = 3.76, 95% CI 1.89-7.41).
      CONCLUSIONS: These results do not support a recommendation of elective caesarean
      section or avoidance of breastfeeding for women with hepatitis C virus infection
      only, but the case for HIV infected women undergoing caesarean section delivery
      and avoiding breastfeeding is strengthened if they are also hepatitis C virus
      infected.

PMID- 11305544
TI  - Epidural compared with general anaesthesia for caesarean delivery in conscious
      women with eclampsia.
AB  - OBJECTIVE: To compare retrospectively the outcome of caesarean section under
      epidural anaesthesia with that of general anaesthesia in "stable" women with
      eclampsia. DESIGN: Retrospective review. METHOD: Over the five-year study period,
      there were 533 women with eclampsia and of these 66 women (12.4%), fulfilled the
      criteria of being 'stable'. Of the 66 women, 37 received epidural, 27 general,
      and 2 spinal anaesthesia. RESULTS: There were no major complications with either
      general or epidural anaesthesia. Epidural anaesthesia was associated with higher
      one-minute Apgar scores. CONCLUSION: This study indicates that both maternal and
      neonatal outcomes are not affected adversely by the use of epidural anaesthesia
      in selected cases of eclampsia.

PMID- 11305545
TI  - Risk factors for third degree perineal ruptures during delivery.
AB  - OBJECTIVE: To determine risk factors for the occurrence of third degree perineal
      tears during vaginal delivery. DESIGN: A population-based observational study.
      POPULATION: All 284,783 vaginal deliveries in 1994 and 1995 recorded in the Dutch
      National Obstetric Database were included in the study. METHODS: Third degree
      perineal rupture was defined as any rupture involving the anal sphincter muscles.
      Logistic regression analysis was used to assess risk factors. MAIN OUTCOME
      MEASURES: An overall rate of third degree perineal ruptures of 1.94% was found.
      High fetal birthweight, long duration of the second stage of delivery and
      primiparity were associated with an elevated risk of anal sphincter damage.
      Mediolateral episiotomy appeared to protect strongly against damage to the anal
      sphincter complex during delivery (OR: 0.21, 95% CI: 0.20-0.23). All types of
      assisted vaginal delivery were associated with third degree perineal ruptures,
      with forceps delivery (OR: 3.33, 95%-CI: 2.97-3.74) carrying the largest risk of
      all assisted vaginal deliveries. Use of forceps combined with other types of
      assisted vaginal delivery appeared to increase the risk even further.
      CONCLUSIONS: Mediolateral episiotomy protects strongly against the occurrence of
      third degree perineal ruptures and may thus serve as a primary method of
      prevention of faecal incontinence. Forceps delivery is a stronger risk factor for
      third degree perineal tears than vacuum extraction. If the obstetric situation
      permits use of either instrument, the vacuum extractor should be the instrument
      of choice with respect to the prevention of faecal incontinence.

PMID- 11305546
TI  - Hysterectomy prevalence and adjusted cervical and uterine cancer rates in England
      and Wales.
AB  - OBJECTIVE: To present recent trends in cervical and uterine cancer adjusted for
      true population at risk, using accurate estimates of the prevalence of
      hysterectomy where the cervix has been removed or not. To describe trends and
      projections of hysterectomy incidence and prevalence with and without cervix
      removal. DESIGN: Collation of available NHS and private sector information.
      SETTING: England and Wales. SAMPLE: NHS operations from Hospital Inpatient
      Enquiry, Hospital Episode Statistics and Hospital Activity Analysis for England
      and Wales. Private sector data from surveys with up to 97% coverage. METHODS AND
      MAIN OUTCOME: Measures NHS data by 5-year age group, year and operation type were
      collated for 1961-1995. non-NHS operations for 1981, 1986, and 1992/3 were back
      projected. Hysterectomy incidence rates, 1961-95, were back-projected to estimate
      prevalence rates by accumulation. True populations at risk of disease and
      hysterectomy were calculated by applying one minus the relevant hysterectomy
      prevalence rates to the population by age group and year. RESULTS: When based on
      the true population at risk, the age standardised cervical cancer incidence rate
      in 1992 was 14.4 per 100,000, compared with 12.6 when based on the all women
      population estimate. Incidence rates for earlier years were also affected, but
      there was no important effect on the rate of change over time. Absolute changes
      for uterine cancer are greater because the true population at risk is
      proportionally smaller particularly at the older ages, but there are again no
      major effects on the rate of change. By 1995 2.3 million women in England and
      Wales were without a uterus, with a peak prevalence of 21.3% in the age group 55
      59. Projections based on 1995 incidence rates show hysterectomy prevalence for
      the screened age groups, 25-64, will now fall. Subtotal hysterectomy is 3.5% of
      operations and increasing. CONCLUSIONS: True populations at risk must be used to
      assess the impact of screening if further reductions in cervix cancer incidence
      rates are not to be masked. It is essential to monitor hysterectomy by type, as
      subtotal hysterectomy is becoming more common. Hysterectomy incidence may have
      peaked. Hysterectomy prevalence in England and Wales may not be as high as would
      be estimated from some regional studies.

PMID- 11305547
TI  - Antibiotic prophylaxis to prevent post-abortal upper genital tract infection in
      women with bacterial vaginosis: randomised controlled trial.
AB  - OBJECTIVE: To determine the prevalence of bacterial vaginosis in women undergoing
      first trimester suction termination of pregnancy and to evaluate the efficacy of
      metronidazole in reducing the risk of post abortal pelvic infection in women with
      bacterial vaginosis. DESIGN: Randomised double-blind placebo-controlled trial.
      SETTING: Two teaching hospitals and one district general hospital. SAMPLE: Two
      hundred and seventy-three women with bacterial vaginosis undergoing termination
      of pregnancy. METHODS: Women with bacterial vaginosis, diagnosed using modified
      Spiegel's criteria, were individually randomised to receive either a 2 g
      metronidazole suppository or identical placebo per-operatively. Participants,
      doctors and investigators were blinded to treatment allocation. Participants were
      asked to complete a questionnaire about post-operative symptoms, visits to the
      general practitioner, antibiotic treatment, readmission to hospital,
      contraception and emotional response after one month. RESULTS: The prevalence of
      bacterial vaginosis was 29.3% (326/1,111). Intention-to-treat analysis showed
      that post-operative upper genital tract infection developed in 12/142 (8.5%)
      women allocated to metronidazole and 21/131 (16.0%) women randomised to placebo,
      a difference of 7.6% (95% confidence intervals -15.4 to +0.2%; relative risk
      0.53. 0.27 to 1.03, P = 0.055). The effect of prophylaxis was similar when the
      analysis was restricted to women receiving the allocated treatment and with
      complete follow up. There was no difference in the risk of readmission to
      hospital and the frequencies of self reported symptoms in the two groups were
      similar. CONCLUSION: This randomised placebo-controlled trial among women with
      bacterial vaginosis provides weak evidence that metronidazole decreases the risk
      of upper genital tract infection after first trimester suction termination of
      pregnancy but a chance finding could not confidently be excluded. Large well
      conducted randomised trials with long term outcome measures are now needed to
      determine the most effective antibiotic combinations and strategy for prevention
      of post-abortal pelvic infection.

PMID- 11305548
TI  - Familial Mediterranean fever and menstruation.
AB  - OBJECTIVE: To study the prevalence, the nature and the genotype correlation of
      menstruation associated familial Mediterranean fever attacks. METHODS: One
      hundred and forty-one female patients with familial Mediterranean fever were
      studied. A questionnaire regarding the presence and nature of menstruation
      associated with familial Mediterranean fever was designed and filled in by the
      authors during the patients' visits to the familial Mediterranean fever clinic.
      The patients who had a positive history for this manifestation were analysed for
      their familial Mediterranean fever mutations. RESULTS: Ten out of 141 familial
      Mediterranean fever female patients (7%) had menstruation-associated familial
      Mediterranean fever attacks. These patients varied in their disease age of onset
      and disease duration. Increase of colchicine dose, daily or during the
      perimenstrual period or oral contraceptives were beneficial in preventing these
      familial Mediterranean fever attacks. No correlation was found with specific
      mutations causing familial Mediterranean fever. CONCLUSIONS: Menstruation
      associated familial Mediterranean fever attacks are relatively uncommon. They are
      not related to the age of the women, the chronicity of their disease or to the
      mutations they bear. Various therapeutic approaches have to be tried in order to
      abolish these attacks. A decrease in oestrogen level during menstruation may have
      a role in this unique manifestation of familial Mediterranean fever.

PMID- 11305549
TI  - A comparison of the objective and subjective outcomes of colposuspension for
      stress incontinence in women.
AB  - OBJECTIVES: To investigate the impact of colposuspension for stress incontinence
      on the symptoms and quality of life of women undergoing both primary and repeat
      surgery for genuine stress incontinence and in addition to assess the use of a
      condition specific quality of life questionnaire as an outcome measure following
      surgery. DESIGN: Prospective case series: videocystourethrography performed
      before and between six and twelve months after surgery. Validated condition
      specific quality of life (QoL) questionnaires completed by women before and six
      to twelve months after surgery. SETTING: A tertiary referral Urogynaecology Unit
      in a teaching hospital. PARTICIPANTS: A consecutive series of 83 women undergoing
      colposuspension between March 1995 and December 1997. Pre-operative assessment
      and surgery was performed by, or was under the direct supervision of, the unit
      director. INTERVENTION: Modified Burch colposuspension. MAIN OUTCOME MEASURES:
      Objective results of surgery assessed with videocystourethrography. Subjective
      results evaluated using a condition specific QoL tool, the Kings Health
      Questionnaire (KHQ). Symptom severity was evaluated as a component of the
      condition specific QoL questionnaire. RESULTS: Objective cure was demonstrated in
      92% of women undergoing primary surgery with an 8% incidence of de-novo detrusor
      instability and a 10% incidence of voiding difficulties. In the group of women
      having repeat surgery the objective cure rate was 81% with no de-novo detrusor
      instability and a 6% incidence of post-operative voiding difficulties. QoL scores
      improved in 95% of women. Improvements of over 25% were seen in 70% of women and
      of over 50% in 28%. However, 2.4% of women recorded a deterioration in QoL
      scores. CONCLUSIONS: Colposuspension performed in this setting, assessed using
      both objective and standardised subjective measures, completed by women
      themselves, appears to produce good objective and subjective results and leads to
      enhanced quality of life in the great majority of women.

PMID- 11305550
TI  - The tension-free vaginal tape procedure is successful in the majority of women
      with indications for surgical treatment of urinary stress incontinence.
AB  - OBJECTIVES: To evaluate the effectiveness and safety of the ambulatory, minimally
      invasive tension-free vaginal tape procedure in women scheduled for incontinence
      surgery. DESIGN: A prospective open study with a standardised protocol for pre-
      and post-operative evaluation. PARTICIPANTS: One hundred and sixty-one
      consecutive women with urodynamically proven stress incontinence. The mean age
      was 56 years; 45 women (28%) had recurrent incontinence, 59 women (37%) had mixed
      incontinence and 18 women (11%) had a low pressure urethra. MAIN OUTCOME
      MEASURES: Subjective and objective cure rates, complications and length of
      hospital stay. RESULTS: The average follow up time was 16 months. Ninety-four
      percent of the treated women were completely cured or significantly improved.
      Eighty percent of the women were released from hospital on the afternoon of the
      day of surgery. There were no major complications and 80.2% of the women had no
      complication at all. Seven women (4.3%) had no more than four days of urinary
      retention problems, five women (3.1%) developed de novo urge symptoms, ten women
      (6.1%) had urinary tract infection, six cases (3.7%) of intraoperative bladder
      perforation occurred and less than 3% had bleeding or infection problems. There
      was no difference in the cure rate between women suffering from primary,
      recurrent or mixed incontinence. CONCLUSIONS: The tension-free vaginal tape
      operation is an effective and safe procedure for treatment of most cases of
      female urinary stress incontinence. The operation can be performed as an
      ambulatory procedure because of the low risk of post-operative morbidity.

PMID- 11305551
TI  - Management of massive postpartum haemorrhage: use of a hydrostatic balloon
      catheter to avoid laparotomy.
AB  - Postpartum haemorrhage remains a significant complication of childbirth in the UK
      and worldwide. The most common cause of postpartum haemorrhage is uterine atony,
      but placent accreta is becoming more frequent. In these situations tamponade may
      be required. The successful use of the inflated stomach balloon (300ml) of a
      Sengstaken-Blakemore tube has been reported previously. We describe an innovative
      method of 'tamponade' which is simple and effective, using the Rusch urological
      hydrostatic balloon catheter. In two cases of failed medical therapy for PPH,
      where the catheter has been tried, further surgical interventions have been
      avoided.

PMID- 11305552
TI  - Use of a portable bladder scanner to reduce the incidence of bladder
      catheterisation prior to laparoscopy.
AB  - The aim of this study was to evaluate the usefulness of estimating bladder volume
      with a dedicated portable ultrasound device immediately prior to gynaecological
      laparoscopy. Catheterisation was performed if the estimated volume was greater
      than 100 ml. Forty consecutive women were studied prospectively. Twenty-six women
      did not require catheterisation. The procedure was quick and effective in safely
      reducing the frequency of pre-operative catheterisation.

PMID- 11305553
TI  - Maternal pyridoxine non-responsive homocystinuria: the role of dietary treatment
      and anticoagulation.

PMID- 11305554
TI  - Ex-utero intrapartum treatment for cervical teratoma.

PMID- 11305555
TI  - Spontaneous hepatic rupture and maternal death following an uncomplicated
      pregnancy and delivery.

PMID- 11305556
TI  - Successful intra-cytoplasmic sperm injection treatments in identical twin
      brothers with severe oligozoospermia.

PMID- 11305557
TI  - An unusual mode of delivery.

PMID- 11305558
TI  - Follow-up of patients with previous treatment for coarctation of the thoracic
      aorta: comparison between contrast-enhanced MR angiography and fast spin-echo MR
      imaging.
AB  - Regular follow-up is required in patients with previous intervention for
      coarctation of the aorta to detect recoarctation or aneurysm formation. In this
      study we describe the findings encountered on routine follow-up exams and we
      compare the use of contrast-enhanced 3D MR angiography (CE MRA) with fast spin
      echo MRI (FSE) to study the thoracic aorta after previous intervention. In 51
      consecutive patients previously treated for aortic coarctation, 74 MR studies of
      the thoracic aorta were performed during a 2-year period using CE MRA and FSE
      MRI. The thoracic aorta was evaluated for abnormalities of course, caliber,
      shape, and pathology of side branches. The CE MRA and FSE MRI studies were
      evaluated side by side by consensus of two reviewers evaluating which MR
      technique depicted the abnormalities of the thoracic aorta the best. Of 74 exams,
      six clinically important abnormalities were found: four aneurysms and two
      restenoses. Two small pseudoaneurysms were missed on the FSE studies. Contrast
      enhanced MRA was judged to visualize aortic abnormalities better than FSE (47 of
      74 MR studies) especially for the transverse aortic arch, coarctation site, left
      subclavian artery, and aortic arch configuration. For the ascending aorta and
      distal descending aorta, CE MRA and FSE performed equally well. Aortic diameters
      measured at four levels in the first 18 MRI studies showed no significant
      differences in diameter when measured by FSE or CE MRA (p = not significant).
      Clinically important abnormalities, such as aneurysm formation and restenosis,
      can be present years after treatment for aortic coarctation. In the regular
      follow-up of these patients, CE MRA may provide additional diagnostic information
      compared with FSE and should be included as part of the routine exam.

PMID- 11305559
TI  - Depiction of anomalous coronary vessels and their relation to the great arteries
      by magnetic resonance angiography.
AB  - Three-dimensional respiratory-gated coronary MR angiography (MRA) allowed
      accurate analysis of the anatomy of the coronary arteries and their relation to
      the adjacent anatomic structures in two patients with anomalous origin and
      proximal course of the coronary vessels. Together with functional tests, it
      decisively influenced further therapy.

PMID- 11305560
TI  - Two-dimensional thick-slice MR digital subtraction angiography for assessment of
      cerebrovascular occlusive diseases.
AB  - Although spatial resolution of current MR angiography is excellent, temporal
      resolution has remained unsatisfactory. We evaluated clinical applicability of 2D
      thick-slice, contrast-enhanced subtraction MR angiography (2D-MR digital
      subtraction angiography) with sub-second temporal resolution in cerebrovascular
      occlusive diseases. Twenty-five patients with cerebrovascular occlusive diseases
      (8 moyamoya diseases, 10 proximal internal carotid occlusions, and 2 sinus
      thromboses ) were studied with a 1.5-T MR unit. The MR digital subtraction
      angiography (MRDSA) was performed per 0.97 s continuously just after a bolus
      injection of 15 ml of gadolinium chelates up to 40 s in sagittal (covering
      hemisphere) or coronal planes. Subtraction images were generated at a
      workstation. We evaluated imaging quality and hemodynamic information of MRDSA in
      comparison with those of routine MR imaging, non-contrast MR angiography, and X
      ray intra-arterial DSA. Major cerebral arteries, all of the venous sinuses, and
      most tributaries were clearly visualized with 2D MRDSA. Also, pure arterial
      phases were obtained in all cases. The MRDSA technique demonstrated prolonged
      circulation in sinus thromboses, distal patent lumen of proximal occlusion, and
      some collateral circulation. Such hemodynamic information was comparable to that
      of intra-arterial DSA. Two-dimensional thick-slice MRDSA with high temporal
      resolution has a unique ability to demonstrate cerebral hemodynamics equivalent
      to that of intra-arterial DSA and may play an important role for evaluation of
      cerebrovascular occlusive diseases.

PMID- 11305561
TI  - Hypoplasia of the internal carotid artery: a noninvasive diagnosis.
AB  - We present the characteristic imaging findings of hypoplasia of the internal
      carotid artery (ICA) in two cases, one accompanied by an intracranial aneurysm.
      Finding of a diffuse luminal narrowing of the ICA on MR angiography or digital
      subtraction angiography (DSA) could wrongly evoke severe acquired diseases such
      as dissection or atherosclerosis. Absence of associated wall thickening and flow
      disturbances on color Doppler sonography (CDS) should suggest carotid hypoplasia.
      Confirmation of the diagnosis is obtained by CT of the skull showing a small
      carotid canal. Non-invasive procedures are sufficient to differentiate this rare
      congenital anomaly from acquired string signs.

PMID- 11305562
TI  - MR imaging findings in granular cell tumor of the neurohypophysis: a difficult
      preoperative diagnosis.
AB  - Granular cell tumor is a rare neoplasm arising within the neurohypophysis. We
      describe the MR imaging findings in two symptomatic patients. In one patient with
      history of panhypopituitarism, MR images showed a large sellar and suprasellar
      mass. The other patient presented with acute loss of vision in her left eye, and
      MR images showed a suprasellar mass with compression of the optic chiasm.

PMID- 11305563
TI  - Acute spontaneous spinal epidural haematoma in a child.
AB  - Spontaneous spinal epidural haematomas rarely occur. Patients tend to be in their
      sixties or seventies. Acute spontaneous spinal epidural haematomas in children
      without a predisposition for bleeding disorders, trauma, vascular malformations
      or anticoagulant therapy have seldom been described. We present a case of a 4
      year-old girl with a spontaneous cervical epidural haematoma diagnosed with MR.

PMID- 11305564
TI  - Hydro-dynamic CT preoperative staging of gastric cancer: correlation with
      pathological findings. A prospective study of 107 cases.
AB  - The aim of this study was to evaluate the accuracy of dynamic CT in the
      preoperative staging of gastric cancer. One hundred seven patients affected by
      gastric cancer diagnosed by endoscopic biopsy were prospectively staged by
      dynamic CT prior to tumor resection. After an oral intake of 400-600 ml of tap
      water and an intravenous infusion of a hypotonic agent, 200 ml of non-ionic
      contrast agent were administered by power injector using a biphasic technique.
      The CT findings were prospectively analyzed and correlated with the pathological
      findings at surgery. The accuracy of dynamic CT for tumor detection was 80 and
      99% in early and advanced gastric cancer, respectively, with overall detection
      rate of 96% (103 of 107). Three early (pT1) and one advanced (pT2) cancers were
      undetected. Tumor stage as determined by dynamic CT agreed with pathological
      findings in 83 of 107 patients with an overall accuracy of 78%. The accuracy of
      CT in detecting increasing degrees of depth of tumor invasion when compared with
      pathological TNM staging was 20% (3 of 15) and 87% (80 of 92) in early and
      advanced cancer, respectively. The sensitivity, specificity, and accuracy of CT
      in the preoperative staging (pT3-pT4 vs pT1-pT2) was 93, 90, and 91.6%,
      respectively. The sensitivity, specificity, and accuracy of CT in assessing
      metastasis to regional lymph nodes was 97.2, 65.7, and 87%, respectively.
      Computed tomography correctly staged liver metastases in 105 of 107 patients with
      an overall sensitivity of 87.5% and specificity of 99 %. The sensitivity of
      peritoneal involvement was 30% when ascites or peritoneal nodules were absent.
      Our findings show that dynamic CTcan play a role in the preoperative definition
      of gastric cancer stage. The results can be used to optimize the therapeutic
      strategy for each individual patient prior to surgery, thus avoiding unnecessary
      intervention and allowing careful planning of extended surgery in eligible
      patients.

PMID- 11305565
TI  - Sonography in acute appendicitis: diagnostic utility and influence upon
      management and outcome.
AB  - A study is made of the diagnostic utility of echography in clinically suspected
      appendicitis, and its influence upon patient management and outcome. A total of
      374 consecutive patients with possible appendicitis were prospectively evaluated
      by ultrasound. Two groups were established: group A (high clinical probability, >
      or =0.70) and group B (moderate clinical probability, 0.20-0.60). In group-A
      patients (n = 105, 28%), prevalence of appendicitis = 0.90) underwent surgery
      regardless of the echographic findings. In group B (n = 269, 72%), prevalence of
      appendicitis = 0.28) surgery was performed in the event of positive echography,
      whereas negative echographic findings did not definitively discard appendicitis.
      The diagnostic utility of echography was evaluated by applying the Pauker-Kasirer
      threshold approach to clinical decision making. The influence of ultrasound upon
      outcome was in turn evaluated by contrasting the total appendectomized patients
      (190 of 374) with a series of 181 individuals subjected to appendectomy prior to
      the introduction of echography. The probability of appendicitis in the presence
      of positive echography was 0.95 in group A (sensitivity = 0.92) and 0.89 in group
      B (sensitivity = 0.91). The probability of appendicitis in the event of negative
      ultrasound was 0.58 in group A (specificity = 0.55) and 0.03 in group B
      (specificity = 0.95) . In 46% of cases the echographic findings led to a change
      in therapeutic regimen. In addition, the incidence of negative appendectomies was
      significantly reduced (19.3 vs 11.6% with echography; p = 0.03), as was the delay
      in establishing a diagnosis (under 6 h in 68.5 vs 84.2% with echography; p =
      0.002) and the number of medical acts required (three in 71.3 vs 84.1% with
      echography; p = 0.001). There was no significant reduction in the incidence of
      perforated appendicitis (17.1 vs 17.9% with echography), in the number of
      postoperative complications (13.8 vs 7.6% with echography), or in the days of
      hospital stay (4.44 vs 4.80 with echography). Echography proved useful in group
      B, and was generally of little utility in group A. The technique had a positive
      influence on treatment, with management reorientation in a considerable number of
      patients, and on outcome, since ultrasound contributed to establishing an earlier
      diagnosis, with a reduction of unnecessary appendectomies.

PMID- 11305566
TI  - Accuracy of enteroclysis in Crohn's disease of the small bowel: a retrospective
      study.
AB  - The aim of this study was to evaluate the accuracy of enteroclysis in the
      diagnosis of Crohn's disease of the small bowel in a group of consecutive
      patients. From January 1992 to December 1995, 165 patients with suspected Crohn's
      disease of the small bowel presented to our institution for enteroclysis. In 14
      patients up to three enteroclysis exams were performed. Most patients (78%)
      underwent colonoscopy and retrograde ileoscopy. In the remaining patients
      clinical follow-up was used as gold standard. In 79 patients no radiographic
      abnormalities were found. Sixty-one patients (40 men and 21 women; mean age 34.2
      years) had a radiological diagnosis of Crohn's disease. This involved the
      terminal ileum in 39 patients (64%) either alone (n = 25) or in association with
      the pelvic ileum (n = 14). In 12 of these patients retrograde ileoscopy was not
      feasible. Twenty-one patients underwent surgery. In 4 patients pathology revealed
      diseases other than Crohn's. These patients had all ileocecal diseases
      (tuberculosis = 2; non-Hodgkin's lymphoma = 1; adenocarcinoma = 1). One false
      negative result was observed. Overall, enteroclysis showed a sensitivity of 98.2%
      and a positive predictive value of 93.4%. Enteroclysis is a sensitive technique
      in evaluating both the extent and the severity of small bowel involvement in
      Crohn's disease, although the overlap of radiographic findings may hamper its
      accuracy when the disease is confined to the ileocecal area.

PMID- 11305567
TI  - Estimation of spleen volume using MR imaging and a random marking technique.
AB  - The aim of this study was to apply a random marking volumetric technique in MR
      images for estimation of spleen volume. The MR imaging was performed in phantoms
      and 16 patients with indications unrelated to splenic disease. Images were
      transferred to a workstation to perform volumetric measurements using the random
      marking technique and the conventional technique of manual planimetry. Two
      observers independently measured splenic volume in order to evaluate
      reproducibility of both volumetric techniques. Phantom experiments revealed that
      the accuracy of the random marking technique and manual planimetry was
      approximately the same. In vivo splenic volume measurements derived from both
      volumetric techniques were highly correlated (r = 0.99, p < 0.0001). For both
      observers intraobserver variation was found to be lower with the random marking
      technique than with manual planimetry. Interobserver coefficient of variation
      using the manual planimetry was 4.6% and was reduced to 2.9% by adopting the
      random marking technique. The random marking technique was almost two times
      faster than the manual planimetry. The combination of the random marking
      technique with MR imaging might provide accurate, reproducible, quick splenic
      volume estimations.

PMID- 11305569
TI  - Castleman's disease in the porta hepatis.
AB  - We report the CT, ultrasonographic, and pathologic features of a localized forms
      of Castleman's disease in the porta hepatis due to their unusual location. Our
      report suggests that the CT and the ultrasonographic features of Castleman's
      disease in these locations without calcifications is nonspecific.

PMID- 11305568
TI  - Hydatid disease with unusual localization.
AB  - Hydatid disease (HD) may develop in almost any part of the body. The liver is the
      most frequently involved organ (75%), followed by the lung (15%) and the
      remainder of the body (10%). Hydatid cysts with unusual localizations may cause
      serious problems in the differential diagnosis. In this article the various
      imaging findings of hydatid cysts with unusual localizations are reviewed, based
      on our experience. Findings in brain, heart, pericard, kidney, intraperitoneum,
      retroperitoneum, bone, soft tissue, and breast are discussed. Hydatid disease
      should be considered in the differential diagnosis of all cystic masses in all
      anatomic locations, especially when they occur in areas where the disease is
      endemic. The combination of clinical history, imaging findings, and serologic
      test results usually help the diagnosis.

PMID- 11305570
TI  - Acute mesenteric ischemia caused by spontaneous isolated dissection of the
      superior mesenteric artery: treatment by percutaneous stent placement.
AB  - Spontaneous and isolated dissection of the superior mesenteric artery is a rare
      and often fatal event which has been successfully treated by surgery in several
      reported cases. We present a patient with acute mesenteric ischemia due to
      superior mesenteric artery dissection who was successfully treated by
      percutaneous endovascular placement of a Wallstent.

PMID- 11305571
TI  - Carpal tunnel syndrome: usefulness of sonography.
AB  - The aim of this study was to evaluate sonographic signs described for carpal
      tunnel syndrome (CTS). Sixty-four wrists from 40 patients with CTS confirmed by
      electromyography, and 42 wrists from 24 healthy individuals, were examined using
      sonography. Cross-sectional area, flattening ratio in proximal, middle and distal
      segments of the carpal median nerve and bowing of the flexor retinaculum were
      measured. The accuracies of the sonographic diagnostic criteria for CTS were
      assessed using receiver-operating-characteristic (ROC) analytical techniques. A
      significant swelling of the median nerve was observed at the proximal (p <
      0.001), middle (p < 0.0001) and distal (p< 0.0001) segments and a significant
      bowing of the flexor retinaculum in CTS patients with respect to healthy
      subjects. No significant differences were found in the mean value of flattening
      ratio between the groups. The sensitivity, specificity, positive predictive
      value, and the negative predictive value were 73.4, 57.1, 72.3 and 58.5%,
      respectively, in the proximal and middle segments; 75, 57.1, 72.7 and 60% in the
      distal segment for areas greater than 11 mm2: and 81.3, 64.3, 77.6 and 69.2% for
      the bowing of the flexor retinaculum greater than 2.5 mm. All sonographic
      criteria were found in 34 CTS patients (53.1%) and none in 3 patients. Sonography
      may be useful in the diagnosis of CTS. The most reliable sign was increased
      bowing of the flexor retinaculum and cross-sectional area of median nerve with
      specificity close to 60%.

PMID- 11305572
TI  - The role of MRI in the assessment of scaphoid fracture healing: a pilot study.
AB  - Twenty-two patients with fracture of the scaphoid treated by cast immobilisation
      underwent clinical examination, radiography and MR scanning 6 weeks after injury.
      On clinical and plain radiographic criteria alone, 12 patients were considered
      sufficiently healed to warrant mobilisation. The remaining 10 patients were
      considered unhealed and were immobilised for a further period. A musculoskeletal
      radiologist, blinded to the clinical diagnosis, reviewed the MRI scans. Of the 10
      patients considered unhealed, 5 had the MR appearances of a united fracture,
      based on normal marrow signal across the fracture line on T1-weighted images. Of
      the 12 patients deemed to have united, union could be confirmed by MRI criteria
      in only 5, but all 12 were healed at 1 year. The results suggest that MRI can
      provide additional information in this group of patients. It can confirm bony
      union in a high proportion of patients deemed clinically non-united. Its use in
      this context will allow a more rapid mobilisation and return to normal function.
      The significance of persistent MR signal abnormalities in patients who have
      clinical and radiographic signs of healing merits further study.

PMID- 11305573
TI  - A longitudinal insufficiency fracture of the tibia in association with a healed
      chronic osteomyelitis.
AB  - Longitudinal stress fracture of the tibia often present with an atypical clinical
      presentation which can be mistaken for osseous tumor or osteomyelitis. We present
      a case of longitudinal stress fracture of the tibia which occurred in a patient
      with healed chronic osteomyelitis of the tibia. Magnetic resonance imaging failed
      to make the correct diagnosis. Accurate diagnosis was only obtained by helical CT
      which showed the longitudinal fracture line. Magnetic resonance imaging showed
      only non-specific signs of bone marrow edema, suggesting recurrence of
      osteomyelitis. Magnetic resonance imaging can be misleading in the absence of
      direct visualization of the fracture line.

PMID- 11305574
TI  - Pulmonary MALT lymphoma: imaging findings in 24 cases.
AB  - The aim of this study was to describe the imaging features of pulmonary mucosa
      associated lymphoid tissue (MALT) lymphoma. The chest radiographs (n = 18) and CT
      scans (n = 17) of 24 patients (18 men and 6 women) aged 27-78 years (mean = 56
      years), with a known diagnosis of pulmonary MALT lymphoma, were retrospectively
      reviewed by two radiologists and the imaging findings are described. Six of the
      24 patients had a history of an autoimmune disorder and 1 patient had acquired
      immune deficiency syndrome. Multiple pulmonary lesions were identified in 19 of
      24 patients (79%) and solitary lesions in 4 of 24 patients (17%). Diffuse
      pulmonary infiltration was present in 1 patient. Lesions included masses or mass
      like areas of consolidation (n = 21) and pulmonary nodules (n = 18). Associated
      findings were air bronchograms, airway dilatation, a positive angiogram sign and
      a halo of ground-glass shadowing at lesion margins. Peribronchovascular
      thickening was also observed, as were hilar or mediastinal lymph node enlargement
      and pleural effusions or thickening. Although rare, the diagnosis of pulmonary
      MALT lymphoma should be considered in patients with the imaging features
      described, particularly when in association with an indolent clinical course or a
      history of autoimmune disease.

PMID- 11305575
TI  - Percutaneous treatment with amphotericin B of mycotic lung lesions from invasive
      aspergillosis: results in 10 immunocompromised patients.
AB  - The aim of this study was to evaluate the efficacy of percutaneous treatment of
      pulmonary lesions from invasive aspergillosis in immunocompromised patients. From
      1992 to 1998, ten patients (seven men and three women; mean age 56 years)
      affected by hematological neoplasms (8 acute myeloid leukemias, 2 non-Hodgkin's
      lymphomas) and post-chemotherapy prolonged neutropenia developed pulmonary
      lesions from invasive aspergillosis. A total of 13 lesions (diameter 2-7 cm,
      median 5 cm) were treated percutaneously due to insufficiency of the high-dose
      i.v. therapy; under CT guidance, a median of 10 cm3 per session of a 1 mg/cm3
      diluted solution of amphotericin B was injected through a fine needle (21-22 G);
      45 sessions overall were performed (one to five per lesion, median four),
      according to the volume of the nodules, tolerance, and complications. The results
      were retrospectively evaluated either radiologically or clinically. Complications
      were cough, mild hemoptysis, and small pneumothorax and/or pleural effusion. No
      major complications occurred. One month after the beginning of treatment, 8
      lesions completely resolved, 4 greatly improved, and 1 was not significantly
      reduced. In all ten patients symptoms improved (eight of ten could restart
      chemotherapy as scheduled). After antiblastic retreatment, 1 patient had mycotic
      recurrence. In our experience transthoracic topical treatment with amphotericin B
      of single or few lung lesions from invasive aspergillosis was effective,
      affording a rapid improvement of the lesions and symptoms, and allowing
      continuation of chemotherapy as scheduled, thereby reducing the risk of
      recurrences.

PMID- 11305576
TI  - Computed tomographic high-attenuation mediastinal lymph nodes after aluminum
      exposition.
AB  - A case with increased computed tomographic densities of mediastinal lymph nodes
      with histologically proven aluminum storage is presented. We suggest
      consideration of aluminosis as differential diagnosis in patients with increased
      native CT densities beyond 50 HU.

PMID- 11305577
TI  - Combination of signal intensity measurements of lesions in the peripheral zone of
      prostate with MRI and serum PSA level for differentiating benign disease from
      prostate cancer.
AB  - The aim of this study was to predict the benign or malignant nature of a
      prostatic lesion by defining a threshold value of signal intensity ratio and a
      limiting value of serum prostate-specific antigen (PSA) in patients with elevated
      PSA level. Twenty-six patients with elevated PSA level and no hypoechogenic
      lesions at endosonography underwent MR imaging using an endorectal body phased
      array coil at 1.5 T (Siemens Magnetom Symphony). A T2-weighted turbo-spin-echo
      (TSE) pulse sequence was applied in a transverse orientation. Two radiologists
      evaluated the images. In the presence of a pathological finding they defined
      regions of interest (ROI) in the suspicious pathological area of the peripheral
      zone and in muscle for reference. The quotient of the two ROIs was calculated and
      then correlated with the actual PSA level. Diagnosis was confirmed by prostate
      biopsy. Ten of 12 patients with quotients smaller than 4 showed cancer at
      histology. Nine of 12 men with cancer proven by biopsy had PSA levels higher than
      10 ng/ml. A significant difference (p < 0.001) was found between the quotients of
      cancer and quotients of chronic prostatitis, fibrosis, or glandular atrophy. The
      accuracy of tumor differentiation of the method was 77%. Measurement of signal
      intensity quotients in the peripheral zone of the prostate in combination with
      knowledge of defined limits of PSA levels the technique could be helpful in
      detecting additional cancer areas for prostate biopsy. False-negative tumor
      results of standard sextant biopsy can be reduced. In men with high PSA values
      the method has a role in differentiating between patients who require prostate
      biopsy and those of clinical observation.

PMID- 11305578
TI  - Adnexal torsion: MR imaging findings of viable ovary.
AB  - We report a case of torsed ovarian cystic tumor, in which contrast-enhanced high
      resolution MR images accurately contributed to the diagnosis of torsion despite
      the lack of symptoms and to the preoperative evaluation of viability of the
      edematous ovary. Accurate preoperative assessment by MR images and prompt
      conservative surgical approach succeeded in salvaging the involved ovary.

PMID- 11305579
TI  - Three-dimensional contrast-enhanced MRI using an intravascular contrast agent for
      detection of traumatic intra-abdominal hemorrhage and abdominal parenchymal
      injuries: an experimental study.
AB  - The aim of this study was to compare the performance of 3D MRI in conjunction
      with an intravascular contrast agent to spiral contrast-enhanced CT, regarding
      the detection of abdominal parenchymal injuries as well as peritoneal hemorrhage
      in an animal model. Liver and kidney injuries were created surgically in six
      female pigs under general anesthesia. All pigs underwent contrast-enhanced spiral
      CT and 3D MR imaging following administration of an intravascular contrast agent
      (NC100150 Injection). Two readers rated their confidence independently on MR and
      CT data sets using a five-point scale for the presence of organ injury and
      hemoperitoneum. Autopsy findings served as standard of reference. Sensitivity and
      specificity for MR in detecting hepatic and renal injuries as well as
      hemoperitoneum was 100%. Computed tomography was less accurate with sensitivity
      and specificity values of 90 and 94%, respectively. Receiver operating
      characteristics (ROC) analysis revealed a higher confidence when interpretation
      was based on MR images. In an animal model 3D MR imaging in conjunction with an
      intravascular contrast agent proved highly accurate in detecting and localizing
      parenchymal injuries to the upper abdomen as well as in detecting intraperitoneal
      blood collections.

PMID- 11305580
TI  - Delayed allergy-like reactions to X-ray contrast media: mechanistic
      considerations.
AB  - Iodinated X-ray contrast media are among the most frequently used pharmaceuticals
      for intravascular administration. Although the newer low osmolality, nonionic
      contrast media, are generally well tolerated, it is well known that they, like
      the ionic contrast media, give rise to immediate or delayed adverse reactions in
      susceptible individuals. In the present review, the delayed allergy-like
      reactions, which by definition occur more than 1 h after contrast medium
      administration, are described, and the possible pathophysiological mechanisms
      discussed. Delayed allergy-like reactions to contrast media, which have been
      reported to occur in 0.5-2% of recipients, are mainly mild to moderate skin
      reactions of the maculopapular exanthematous and urticarial/angioedematous types.
      Most of the reactions become apparent after a latency of 3 h to 2 days and
      disappear within 1 week. The incidence of more severe reactions is extremely low.
      Main risk factors for delayed allergy-like reactions appear to be a previous
      contrast medium reaction, a history of allergy, IL-2 treatment and being of
      Japanese descent. At present, the exact pathogenesis of these delayed reactions
      is still unclear. There is, however, increasing evidence that a significant
      proportion of the reactions are T-cell mediated.

PMID- 11305581
TI  - Report generation using digital speech recognition in radiology.
AB  - The aim of this study was to evaluate whether the use of a digital continuous
      speech recognition (CSR) in the field of radiology could lead to relevant time
      savings in generating a report. A CSR system (SP6000, Philips, Eindhoven, The
      Netherlands) for German was used to transform fluently spoken sentences into
      text. Two radiologists dictated a total of 450 reports on five radiological
      topics. Two typists edited those reports by means of conventional typing using a
      text editor (WinWord 6.0, Microsoft, Redmond, Wash.) installed on an IBM
      compatible personal computer (PC). The same reports were generated using the CSR
      system and the performance of both systems was then evaluated by comparing the
      time needed to generate the reports and the error rates of both systems. In
      addition, the error rate of the CSR system and the time needed to create the
      reports was evaluated. The mean error rate for the CSR system was 5.5%, and the
      mean error rate for conventional typing was 0.4%. Reports edited with the CSR, on
      average, were generated 19% faster compared with the conventional text-editing
      method. However, the amount of error rates and time savings were different and
      depended on topics, speakers, and typists. Using CSR the maximum time saving
      achieved was 28% for the topic sonography. The CSR system was never slower, under
      any circumstances, than conventional typing on a PC. When compared with a
      conventional manual typing method, the CSR system proved to be useful in a
      clinical setting and saved time in generating radiological reports. The amount of
      time saved, however, greatly depended on the performance of the typist, the
      speaker, and on stored vocabulary provided by the CSR system.

PMID- 11305582
TI  - Initial technical and clinical evaluation of a new universal image receptor
      system.
AB  - The aim of this study was to evaluate the physical performance of an experimental
      flat-panel digital X-ray detector plate (FDXD), and to assess its clinical
      potential in radiographic and fluoroscopic mode. The efficiency of the detector
      was assessed by calculating the low-frequency detective quantum efficiency
      (DQE(0)), and a measure of image quality was obtained using a threshold contrast
      detail detectability (TCDD) test object. A range of clinical examinations were
      also carried out, and the results reviewed by members of the radiology staff. The
      DQE(0) of the system was calculated to be almost 75%, compared with a value of
      approximately 20 % for modern computed radiography equipment, offering the
      potential for increased image quality or significant dose reduction. Measurements
      using the TCDD test object demonstrated a corresponding advantage for the FDXD in
      image quality and dose efficiency. Clinical studies are producing radiographic
      results which are at least the equal of the best currently available digital
      technology, and a limited number of examinations using fluoroscopic mode at 25
      frames per second have been equally encouraging. Equipment using FDXD technology
      could potentially fulfill all the radiographic and fluoroscopic requirements of
      the digital department, with improved image quality and dose efficiency.

PMID- 11305583
TI  - A Nordic survey of patient doses in diagnostic radiology.
AB  - The aim of this study was to test the applicability of the guidance levels for
      patient doses cooperatively set by the radiation protection authorities in the
      five Nordic countries. The kerma-area product (KAP) for five conventional
      radiological examination types was obtained from several hospitals in each of the
      Nordic countries. The number of radiographic images and fluoroscopy time were
      also registered, and the mean values for each examination type and hospital were
      established based on a representative number of patients (40-100 kg). The results
      indicate that the situation is very similar in the five Nordic countries, even
      though some differences were identified. Most of the hospitals demonstrated lower
      doses than the proposed guidance levels for chest, probably explained by use of
      faster film/screen combinations during the past decade. An increased use of
      fluoroscopy for positioning was observed for radiographic examinations of lumbar
      spine and urography. Large variations in patient doses were found for barium
      enema depending on the use of fluorospot or 100-mm camera vs full-format film,
      the range in fluoroscopy times, dose rate, and field size. The guidance levels
      for lumbar spine (10 Gy x cm2), pelvis (4 Gy x cm2), urography (20 Gy x cm2), and
      barium enema (50 Gy x cm2) seem to reflect the present quality of X-ray equipment
      and examination techniques in the Nordic countries. The guidance levels for chest
      (1 Gy x cm2) should be lowered to 0.6 Gy x cm2.

PMID- 11305584
TI  - Liver capsular retraction--not a specific sign of malignancy: a reminder.

PMID- 11305585
TI  - A giant cardiac hydatid cyst located in the left ventricle of the heart: MR
      imaging features.

PMID- 11305587
TI  - Quiz case of the month. Pulmonary arteriovenous malformation.

PMID- 11305586
TI  - Accumulation of superparamagnetic iron oxide and technetium-99m-galactosyl human
      serum albumin in a large regenerative nodule.

PMID- 11305588
TI  - Determination of topotecan by ELISA.
AB  - A highly sensitive ELISA for the determination of (s)-9-dimethylaminomethyl-10
      hydroxy-camptothecin (topotecan) capable of measuring as low as 80 pg/ml was
      developed. Anti-topotecan antibody was obtained by immunizing rabbits with
      topotecan conjugated with bovine serum albumin using diazotized m-aminobenzoic
      acid as a cross-linker. Enzyme labeling of topotecan with beta-D-galactosidase
      was performed by utilizing another cross-linker, N-(4-diazophenyl)maleimide. The
      specificity of this ELISA appears to be primarily toward the lactone moiety of
      topotecan, showing a very slight cross-reactivity with the lactone opened-ring of
      topotecan. The values for the topotecan concentrations detected using this assay
      were comparable with those detected using HPLC. There was a good correlation
      between the values determined by the two methods. These findings suggest that
      this ELISA can detect the natural amounts of the lactone form. Using this assay,
      drug levels were easily determined in the blood and urine of rats for 5 h after
      i.v. administration of topotecan at a single dose of 1 mg/kg. The sensitivity and
      specificity of the ELISA should provide a useful tool for developing
      pharmacokinetic and pharmacodynamic studies of topotecan.

PMID- 11305589
TI  - Orthovanadate decreases leptin secretion from isolated mouse fat pads.
AB  - When isolated mouse fat pads were incubated with orthovanadate (vanadate) or
      insulin for up to 4 h, the leptin secretion into the medium was decreased by
      vanadate and increased by insulin. Propranolol, a nonspecific antagonist of beta
      adrenergic receptors, bupranorol, a specific antagonist of beta3-adrenergic
      receptor, and H-89, an inhibitor of cAMP-dependent protein kinase (PKA) all
      inhibited the decrease by vanadate to various extents. In contrast, no inhibition
      was observed with specific antagonists of beta1- and beta2-adrenergic receptors
      or with inhibitors of protein kinase C and Ca/calmodulin kinase. Short-term
      incubation of the fat pads with vanadate showed a transient increase in the
      cellular cAMP content; this increase was inhibited by propranolol and bupranolol.
      Vanadate had no effect on the incorporation of [3H]-leucine into proteins of the
      fat pads with a 4-h incubation, although insulin stimulated the incorporation.
      The decreasing effect of vanadate on the leptin secretion seems to be independent
      of the regulation of protein synthesis. These results suggest that vanadate
      decreases the leptin secretion through mechanisms involving the increase in
      cellular cAMP content via beta3-adrenergic receptor, probably leading to the
      activation of PKA.

PMID- 11305590
TI  - 19-Oxygenation of C19-steroids with an A, B-ring enone structure, competitive
      inhibitors of estrogen biosynthesis, with human placental aromatase.
AB  - Aromatase is a cytochrome P-450 enzyme complex that catalyzes the conversion of
      androst-4-ene-3,17-dione (AD) to estrone through three sequential oxygenations of
      the 19-methyl group. To gain insight into the ability of AD isomers, 4-en-6-one
      1a, 5-en-4-one 2a, and 5-en-7-one 3a, competitive inhibitors of aromatase with an
      A, B-ring enone structure to serve as a substrate, we incubated the three
      inhibitors separately with human placental aromatase in the presence of NADPH in
      air. The metabolites were analyzed as the methoxime-trimethylsilyl ethers by gas
      chromatography-mass spectrometry. All of the inhibitors were found to be
      oxygenated with aromatase to produce the corresponding 19-hydroxy derivatives 1b,
      2b, and 3b with rates of 2.0, 51, and 0.3 pmol/min/mg protein, respectively. Only
      in the experiment with the 5-en-4-one steroid 2a, the production of the 19-oxo
      metabolite 2c was detected with a rate of 3.1 pmol/min/mg protein. The 19
      oxygenation of steroid 2a, the best substrate for aromatase among the three, was
      kinetically determined to give the Vmax value of 40 pmol/min/mg protein and the
      Km value of 1.43 microM, respectively. The results reveal that a good inhibitor
      of aromatase is not essentially a good substrate for the enzyme in a series of
      the A, B-ring enone steroids.

PMID- 11305591
TI  - Chelation of cellular Cu(I) raised the degree of glyoxalase I inactivation in
      human endothelial cells upon exposure to S-nitrosoglutathione through
      stabilization of S-nitrosothiols.
AB  - This study aimed to examine molecular mechanisms responsible for the metabolic
      fate of S-nitrosoglutathione (GSNO) in endothelial cells. After addition of 1 mM
      GSNO in culture medium, concentration of S-nitrosothiols (RSNO) significantly
      decreased with concomitant accumulation of nitrite (NO2-) only in the presence of
      human endothelial cells (ECV304), while no change in RSNO decomposition and NO2-
      accumulation was observed in case of S-nitrosocysteine. Bathocuproine disulfonic
      acid (BCS), a chelator for Cu(I), prevented the cell-mediated decomposition of
      RSNO and accumulation of NO2-. Chelator for Cu(III), Fe(II), or Fe(III);
      inhibitors of gamma-glutamyltranspeptidase; or a superoxide quenching enzyme had
      no effect on the cell-mediated degradation of RSNO and accumulation of NO2-.
      These results indicate that cellular Cu(I) would play a major role in the
      conversion of GSNO into NO2-. We recently demonstrated that human glyoxalase I
      (Glo I) interacts with GSNO in vitro and within cells. When Glo I interacts with
      GSNO, Glo I is inactivated and is chemically modified with pI alteration on 2D
      gels. So, we examined effect of Cu(I) chelation on the Glo I response. As a
      result, chelation of cellular Cu(I) by BCS enhanced the inactivation and chemical
      modification of Glo I by GSNO. The Glo I response could be detected when the
      cells were exposed to GSNO at 10 microM, corresponding to the concentration of
      RSNO under physiological conditions, with pretreatment of BCS. Metal chelators
      for copper and iron ions had no effect on the sensitivity of Glo I to an nitric
      oxide (NO) radical donor. These results indicate that chelation of cellular Cu(I)
      potentiates the sensitivity of GIo I to GSNO. The observation in the present
      study implicates that intracellular levels of GSNO might be elevated,
      accompanying with stabilization of extracellular RSNO.

PMID- 11305592
TI  - Improvement of separation method of fragmented DNA from an apoptotic cell DNA
      sample for the quantitation using agarose gel electrophoresis.
AB  - In order to quantify fragmented DNA extracted from apoptotic cells, we devised a
      separation method which condenses fragmented DNA into a small band, separating it
      from larger-size DNA with agarose gel electrophoresis. Calf thymus DNA and
      standard fragmented DNA were loaded onto 1.0% gel for 0.5, 1.0, 1.5 and 2.0 cm
      length, and onto 0.7, 1.0, 1.5 and 2.0% of gels for 1 cm length. DNA was then
      extracted from gel slices with the UltraClean 15 DNA Purification Kit, and
      estimated by measuring fluorescence intensity using Hoechst No.33258 dye. DNA
      recovery from the gel showed constant values regardless of the amount of loaded
      DNA up to 1 microg/assay, and a plot of loaded DNA amounts vs. the DNA amount
      yielded resulted in a strait line in any gel concentration used. Our results show
      the best conditions to estimate DNA fragmentation rates in apoptotic cells in
      which fragmented DNA was separated from thymus DNA by loading on 1.0% gel for 1.0
      cm length. We used our method to estimate fragmentation rates in DNA fractions
      extracted from apoptotic human cervical fibroblast, amnion epithelial and chorion
      laeve trophoblast cells by stimulation with actinomycin D. The results show that
      DNA fragmentation rates in these cells were consistent with the electrophoretic
      patterns of the DNA samples shown by their photographs.

PMID- 11305593
TI  - L-glutamate suppresses astrocyte stellation induced by actin breakdown in
      culture.
AB  - We have recently found that L-glutamate suppresses morphological changes of
      astrocytes induced by amyloid beta protein, adenosine 3',5'-cyclic monophosphate
      or phorbol ester in culture. To test the possibility that L-glutamate affects
      organization of the cytoskeleton, we investigated its effect on morphological
      changes induced by disruption of actin filaments with cytochalasin B. Cultured
      rat cortical astrocytes exhibited flat, polygonal morphology in the absence of
      stimulation, and changed into process-bearing stellate cells following treatment
      with cytochalasin B (50 microM). L-Glutamate strongly suppressed the stellation
      induced by cytochalasin B. The effect of L-glutamate was mimicked by D- and L
      aspartate and transportable glutamate uptake inhibitors. These results suggest
      that glutamate transporter activity leads to cytoskeletal actin organization in
      astrocytes.

PMID- 11305594
TI  - Interaction of phytoestrogens with estrogen receptors alpha and beta.
AB  - The human estrogen receptor (hER) exists as two subtypes, hER alpha and hER beta,
      that differ in the C-terminal ligand-binding domain and in the N-terminal
      transactivation domain. In this study, we investigated the estrogenic activities
      of soy isoflavones after digestion with enteric bacteria in competition binding
      assays with hER alpha or hER beta protein, and in a gene expression assay using a
      yeast system. The estrogenic activities of these isoflavones were also
      investigated by the growth of MCF-7 breast cancer cells. Isoflavone glycoside
      binds weakly to both receptors and estrogen receptor-dependent transcriptional
      expression is poor. The aglycones bind more strongly to hER beta than to hER
      alpha. The binding affinities of genistein, dihydrogenistein and equol are
      comparable to the binding affinity of 17 beta-estradiol. Equol induces
      transcription most strongly with hER alpha and hER beta. The concentration
      required for maximal gene expression is much higher than expected from the
      binding affinities of the compounds, and the maximal activity induced by these
      compounds is about half the activity of 17 beta-estradiol. Although genistin
      binds more weakly to the receptors and induces transcription less than does
      genistein, it stimulates the growth of MCF-7 cells more strongly than does
      genistein.

PMID- 11305595
TI  - Diesel exhaust particle-induced cell death of human leukemic promyelocytic cells
      HL-60 and their variant cells HL-NR6.
AB  - The cytotoxicity of diesel exhaust particles (DEPs) toward human leukemic
      promyelocytic cells HL-60 was examined. DEPs were toxic and cytotoxicity
      increased in a dose-dependent manner. All cells died with 750 microg/ml DEPs in
      culture media. Apoptosis occurred in HL-60 cells exposed to DEPs. The
      cytotoxicity of DEP extracts with organic solvents was much lower than those of
      DEPs and organic solvent-washed residual DEPs. HL-NR6 cells, an HL-60 variant
      cell line, having higher superoxide dismutase and catalase activities than HL-60
      cells, were more resistant to DEP cytotoxicity. When preincubated with the
      fluorescent probe diacetoxymethyl 6-carboxy-2',7'-dichlorodihydrofluorescinate
      diacetate and then exposed to DEPs, HL-60 cells emitted green fluorescence under
      blue illumination, indicating that reactive oxygen species were generated within
      the cells. The DEP cytotoxicity correlated inversely with the cellular
      concentration of reduced glutathione (GSH), which had been attenuated with L
      buthionine-(R,S)-sulfoximine, a gamma-glutamylcysteine synthetase inhibitor, and
      was lowered with ethyl reduced glutathionate, a GSH carrier across biomembranes.
      Further, DEPs themselves decreased the cellular concentration of GSH in a dose
      dependent manner. The alpha-tocopherol model compound 2,2,5,7,8
      pentamethylchroman-6-ol decreased DEP cytotoxicity, while alpha-tocopherol had no
      effect. In addition, quinacrine, an endocytosis inhibitor, decreased DEP
      cytotoxicity. These results show that DEPs are cytotoxic and suggest that the
      cytotoxicity results from generation of reactive oxygen species by DEPs which
      have been incorporated into cells.

PMID- 11305596
TI  - Spasmolytic activity of methyl angolensate: a triterpenoid isolated from
      Entandrophragma angolense.
AB  - Entandrophragma angolense is a medicinal plant used in folk medicine against
      several diseases including peptic ulcer. Methyl angolensate was isolated from E.
      angolense by recrystallization from methanol. The needle-like crystals were
      characterized and tested on isolated rabbit jejunum, guinea pig ileum and the rat
      fundus strip. The compound was also evaluated on the gastrointestinal transit in
      mice. The results showed that the compound exerted significant concentration
      dependent inhibition of smooth muscle and reduced the propulsive action of the
      gastrointestinal tract in mice. The relaxation observed did not attenuate
      acetylcholine and histamine induced contractions, but was found to inhibit
      contractions induced by serotonin. It is therefore suggested that methyl
      angolensate may exert its activity on gastrointestinal smooth muscle via
      serotonergic mechanisms.

PMID- 11305597
TI  - Comparative study on reduction of bone loss and lipid metabolism abnormality in
      ovariectomized rats by soy isoflavones, daidzin, genistin, and glycitin.
AB  - The effects of the soy isoflavone glycoside, daidzin, genistin, and glycitin on
      bone loss and lipid metabolism in ovariectomized (ovx) rats were compared with
      those of estrone. Thirty-six 11-week-old female Sprague-Dawley rats were assigned
      to six groups, sham-operated, ovx, ovx+glycitin, ovx+daidzin, ovx+genistin, and
      ovx+estrone and fed matched amounts of a commercial calcium-deficient diet for 4
      weeks. Throughout this period, daidzin, genistin or glycitin (25, 50 or 100
      mg/kg/d) was given orally using a stomach tube, or estrone (7.5 microg/kg/d) was
      administered subcutaneously. Daidzin, genistin and glycitin significantly
      prevented bone loss in ovx rats at a dose of 50 mg/kg/d, like estrone. At this
      dose glycitin and daidzin also prevented ovx-induced uterine atrophy and
      increases in body weight gain, abdominal fat, serum total cholesterol and
      triglyceride, and urinary excretion of pyridinoline and deoxypyridinoline with
      statistical significance, like estrone. On the other hand, genistin prevented ovx
      induced uterine atrophy only at a dose of 100 mg/kg, but did not block any other
      change of ovx rats at a dose of 50 or 100 mg/kg. These findings indicate that
      daidzin, glycitin, and genistin are effective in preventing bone loss and the
      former two compounds are effective in reversing the unfavorable changes of lipid
      metabolism in this model. It is suggested that the preventive effect of daidzin
      or glycitin on bone loss in ovx rats is due to suppression of bone turnover, as
      in the case of estrone, but genistin has a different mechanism of action from the
      other compounds. Soy isoflavone glycosides may represent a potential alternative
      therapy in the treatment of bone loss and lipid metabolism abnormality in ovarian
      hormone-deficient women.

PMID- 11305598
TI  - Molecular cloning, functional expression and characterization of d-limonene
      synthase from Schizonepeta tenuifolia.
AB  - Limonene is one of the most simple cyclic monoterpenes, and two enantiomers, d-
      and l-limonene occur due to the chiral carbon at 4-position. Cyclization of GPP
      into limonene is catalyzed by the limonene synthase, and some l-limonene synthase
      cDNAs have already been cloned from several species of plants, mainly from
      Labiatae family. However, the d-limonene synthase gene has not yet been obtained,
      therefore, no information is available on the molecular mechanism of
      stereochemical regulation in limonene formation. To resolve this, we cloned the d
      limonene synthase gene (dLMS) from Schizonepeta tenuifolia (Labiatae) by a
      reverse genetic approach, and we found that both d- and l-limonene synthase share
      similar features such as a transit peptide, an arginine rich domain, and a metal
      cation binding site in their structures. Here, we report on the cloning of dLMS,
      and the putative stereochemical regulation mechanism is discussed based on the
      comparison of the deduced amino acid sequence of dLMS with those of known l
      limonene synthases.

PMID- 11305599
TI  - Study on glutathionesulphonic acid as biodistribution promoter: concomitant use
      effect on verapamil hydrochloride and tegafur.
AB  - The effect of glutathionesulphonic acid (N-(N-gamma-L-glutamyl-L-beta
      sulphoalanylglycine, GSO3H), which is one of the minor metabolites of glutathione
      (GSH), on the pharmacokinetics of verapamil hydrochloride (verapamil x HCl) and
      tegafur was investigated in rats. GSO3H was concomitantly used as sodium salt
      (GSO3Na). No significant change by the concomitant use of GSO3Na was recognized
      in the pharmacokinetics parameters of verapamil x HCl and tegafur, and plasma
      elimination of both substances was not affected by GSO3Na. The tissue-to-plasma
      concentration ratio (Kp) of verapamil x HCl in the lung 5 min after its
      administration under concomitant use of GSO3Na rose significantly, however, this
      effect disappeared 120 min after administration. No significant change was
      recognized in other organs. On the other hand, a significant difference of Kp of
      tegafur under a steady state concentration of GSO3Na was not recognized in any
      organs. It seemed that the elevation of a lipid solubility (oil water partition
      coefficient) of verapamil x HCl by the concomitant use of GSO3Na was related to
      the increase of the Kp value of verapamil x HCl in the lung. The partition
      coefficient of GSO3Na itself decreased when it was used concomitantly with
      verapamil x HCl.

PMID- 11305600
TI  - Evaluation of insulin permeability and effects of absorption enhancers on its
      permeability by an in vitro pulmonary epithelial system using Xenopus pulmonary
      membrane.
AB  - The permeability of insulin across Xenopus pulmonary membrane and the effects of
      various absorption enhancers on insulin permeability were examined using an in
      vitro Ussing chamber technique. Absorption enhancers used in this study were
      sodium caprate (NaCap), sodium glycocholate (NaGC), sodium salicylate (NaSal) and
      ethylenediaminetetraacetic acid disodium salt (EDTA). The permeability of insulin
      across Xenopus pulmonary membrane significantly increased in the presence of
      NaCap and NaGC, while EDTA and NaSal did not enhance the permeability. In
      addition, the enhancing effect of NaGC increased as the concentrations of these
      enhancers increased. Transmembrane resistance (Rm) of Xenopus lung was markedly
      decreased in the presence of these enhancers, and NaCap showed a greater effect
      on Rm than NaGC. Furthermore, the amount of alkaline phosphatase (ALP) and
      lactate dehydrogenase (LDH) released from the apical side of the Xenopus
      pulmonary membrane increased in the presence of these enhancers. These results
      indicate that NaCap and NaGC improve the pulmonary absorption of insulin, but
      they are toxic to the pulmonary membrane. These findings suggest that this method
      is useful for estimating the permeability characteristics of peptides across the
      pulmonary membrane and for evaluating the effects of various additives on their
      permeability and their membrane toxicity.

PMID- 11305601
TI  - Influence of electrical and chemical factors on transdermal iontophoretic
      delivery of three diclofenac salts.
AB  - The aim of this present study was to investigate the in vitro transdermal
      iontophoretic delivery of three diclofenac salts--diclofenac sodium (DFS),
      diclofenac potassium (DFP), and diclofenac diethylammonium (DFD). A series of
      physicochemical and electrical variables which might affect iontophoretic
      permeation of diclofenac salts was studied. Application of 0.3 mA/cm2 current
      density significantly increased the transdermal flux of diclofenac salts as
      compared to passive transport. The iontophoretic enhancement increased in the
      order of DFS>DFP>DFD. The permeability coefficient of diclofenac salts all
      decreased with increasing donor concentration during iontophoresis. The addition
      of buffer ions and salt ions such as NaCl, KCl, and C4H12ClN reduced the
      permeation of diclofenac salts due to competition. However, this effect was
      lesser for DFD than for DFS and DFP. Comparing the various application modes of
      iontophoresis, the discontinuous on/off mode showed lower but more constant flux
      than the continuous mode.

PMID- 11305602
TI  - A moderate interaction of maltosyl-alpha-cyclodextrin with Caco-2 cells in
      comparison with the parent cyclodextrin.
AB  - The cytotoxicity of maltosyl-alpha-cyclodextrin (G2-alpha-CyD) and maltosyl-beta
      cyclodextrin (G2-beta-CyD) toward Caco-2 cells was compared with that of natural
      alpha-cyclodextrin (alpha-CyD), beta-cyclodextrin (beta-CyD) and gamma
      cyclodextrin (gamma-CyD). The degree of increase in cytotoxicity was dependent on
      the CyD's type and the concentration: the cytotoxicity of CyDs at the same
      concentration increased in the order of gamma-CyD<G2-beta-CyD<G2-alpha-CyD<<alpha
      CyD, although beta-CyD could not be compared to other CyDs because of low
      solubility in water. Alpha-CyD decreased transepithelial electrical resistance
      (TEER) and increased the apical-to-basolateral (AP-to-BL) transport of
      [3H]mannitol, a paracellular transport marker, in a concentration-dependent
      manner, suggesting that alpha-CyD decreased the integrity of Caco-2 cell
      monolayers. In addition, alpha-CyD increased the AP-to-BL transport of rhodamine
      123, a transcellular transport marker, under the experimental conditions being
      independent of P-glycoprotein. In contrast, G2-alpha-CyD, G2-betaCyD and gamma
      CyD had slight effect on both TEER and the transport of mannitol and rhodamine
      123 even at relatively high concentrations up to 150 mM. The inability of G2
      alpha-CyD and G2-beta-CyD to effect TEER and the transport of mannitol and
      rhodamine 123 could be explained by the findings that these maltosylated CyDs
      released only a small amount of membrane constituents from Caco-2 cell monolayers
      and interacted only weakly with monolayers composed of L-alpha
      dipalmitoylphosphatidylcholine (DPPC) formed on water. These results indicate
      that G2-alpha-CyD has less cytotoxicity and less disturbing ability toward Caco-2
      cell monolayers than alpha-CyD, and G2-beta-CyD has, at least, comparable
      cytotoxicity to beta-CyD toward them. Thus, from the safety point of view, highly
      water-soluble G2-alpha-CyD and G2-beta-CyD may be particularly useful in various
      pharmaceutical formulations.

PMID- 11305603
TI  - Factors influencing the prediction of steady state concentrations of digoxin.
AB  - The prediction error in the Bayesian analysis program for digoxin was evaluated
      in Japanese patients, and factors influencing the accuracy were investigated.
      Serum concentrations of digoxin were monitored two times and were compared with
      the predicted values obtained by using the Bayesian analysis program. The
      prediction error at the first time was 43.1%. Although this estimation error was
      reasonably restored at the second time of monitoring, the prediction error
      remained at 26.6%. These data suggested that unknown factors not included in the
      program affected the serum concentration of digoxin. Retrospective research of
      the digoxin serum concentrations in the patients suggested the coadministration
      of the drugs, which were the P-glycoprotein modulators, as well as the unexpected
      alteration of the serum creatinine, were the important factors influencing the
      prediction of the drug serum concentrations. We next examined the inhibitory
      effect of quinidine, verapamil and spironolactone on the transcellular transport
      of digoxin by using human P-glycoprotein overexpressing LLC-GA5-COL150 cells.
      Quinidine, verapamil and spironolactone could inhibit the transcellular transport
      of digoxin by 50%. In addition, the reduction of the renal clearance by 50%,
      which could possibly be caused by this inhibition, led to the increase of 36% in
      the steady state through concentrations of digoxin in the physiological
      pharmacokinetic model. In conclusion, the prediction of long-term serum
      concentration-time profiles of digoxin, based on the Bayesian analysis, will be
      disturbed by the coadministration of the P-glycoprotein modulators and the
      unexpected alteration of the serum creatinine.

PMID- 11305604
TI  - Changes in the dissolution of tolbutamide by a traditional Chinese medicine, Sho
      saiko-to (Xiao Chaihu Tang).
AB  - Dissolution rate is considered an important factor affecting absorption and
      efficacy after the oral administration of tolbutamide. Since in many cases
      traditional Chinese medicines, including Sho-saiko-to (TJ-9, Xiao Chaihu Tang),
      are taken with other drugs, it is likely that the dissolution and absorption of
      concomitant drugs in the gastrointestinal tract are influenced by the presence of
      traditional Chinese medicines. In this study, the effects of TJ-9 on the in vitro
      dissolution of tolbutamide were examined. We carried out the dissolution test of
      tolbutamide in the absence or presence of traditional Chinese medicines (Kakkon
      to, TJ-1; Hachimi-jio-gan, TJ-7; Chorei-to, TJ-40; Shakuyaku-kanzo-to, TJ-68; TJ
      9; Glycyrrhizae Radix, GR; glycyrrhizin, GL) by using a pH 1.2 dissolution
      medium. Tolbutamide was determined by HPLC assay. The moment parameters, ie.,
      mean dissolution time (MDT), and the dissolution rate constant up to 20 min (kd)
      were estimated from the dissolution profiles on the basis of the first-order
      kinetics. Preparations containing GR, namely TJ-1, TJ-9 and TJ-68, significantly
      reduced the kd and increased the MDT of tolbutamide, while TJ-7 and TJ-40 had no
      effect on the early dissolution profile of tolbutamide. The extent of decrease in
      the kd in the presence of TJ-1, TJ-9 and TJ-68 was dependent on their GR
      contents. Similar inhibitory effects on the dissolution rate of tolbutamide were
      observed when GR alone was added to the test medium. In addition, GL, a major
      constituent of GR, induced a 50% increase in MDT and a 30% decrease in kd. The
      above results indicate that Chinese traditional preparations containing GR have
      an inhibitory effect on the in vitro dissolution of tolbutamide, which is derived
      from GL in the preparations.

PMID- 11305605
TI  - Age difference in simultaneous permeation and metabolism of ethyl nicotinate in
      rat skin.
AB  - The age-dependent characteristics of transdermal permeation of ethyl nicotinate
      (EN) and its metabolism to nicotinic acid (NA) were examined in rats at the ages
      of a fetus at 21 d, 3, 10, 50, 270 and 360 d. Skin transport in vitro was
      investigated using mounted skin in side-by-side diffusion chambers, and flux of
      EN and NA was determined. With developing and aging in rats, EN flux from EN
      saturated solution declined gradually, however, NA flux increased drastically at
      10 and 50 d. To elucidate the mechanism of this age-dependent escalation of NA
      flux, a hydrolysis study was performed using skin homogenate, and the Michaelis
      Menten parameters (Vmax and Km) of EN were evaluated. Vmax and Vmax/Km ratio
      showed the same tendency with NA flux/total (EN+NA) flux ratio, suggesting that
      skin esterases in rats are developed gradually after birth, then increase
      markedly and become steady in the adult period. On the other hand, the affinity
      parameter, Km, was almost the same among all ages. Moreover, metabolic saturation
      of esterase during the transdermal process occurred in all ages, and maximal NA
      flux and EN concentration in the donor compartment for the maximal NA flux were
      also affected by age. These findings indicated that the discrepancy in
      transdermal profiles of EN among the ages tested was dominantly due to the
      difference in the development of esterase in the growth process.

PMID- 11305606
TI  - Involvement of reactive oxygen species in hemoglobin oxidation and virus
      inactivation by 1,9-dimethylmethylene blue phototreatment.
AB  - The participation of reactive oxygen species (ROS) in virus inactivation by 1,9
      dimethylmethylene blue (DMMB) phototreatment in stroma-free hemoglobin (SFH) was
      investigated with the use of scavengers, quenchers and enhancer. Virus (R17
      bacteriophage) photoinactivation by either activated monomer or dimer DMMB was
      suppressed by sodium azide (singlet oxygen quencher) and promoted by the
      substitution of H2O for deuterium oxide (D2O), which is known to prolong the
      lifespan of singlet oxygen. There was no or little effect of mannitol (hydroxyl
      radical scavenger) and superoxide dismutase (superoxide scavenger) on the
      photoinactivation. Similar experiments were conducted to investigate the
      mechanism of methemoglobin (Met-Hb) formation by the activated monomer of DMMB.
      There was little effect of the singlet oxygen quencher, histidine, or the
      enhancer, D2O, on Met-Hb formation. However, rutin, which inhibits not only
      singlet oxygen but also other ROS, and mannitol supressed the formation of Met-Hb
      by activated monomer. The addition of superoxide dismutase (SOD) did not inhibit
      the formation. In contrast to the activity of the DMMB monomer, that of the dimer
      was inhibited by histidine and enhanced by D2O. The addition of neither mannitol
      nor SOD affected Met-Hb formation by activated dimer. These results collectively
      suggest that virus photoinactivation by the activated monomer and dimer of DMMB
      as well as Met-Hb formation by the activated dimer proceed via a singlet oxygen
      mediated pathway. In contrast, singlet oxygen may play a less important role in
      Met-Hb formation by the activated monomer.

PMID- 11305607
TI  - Enzyme immunoassay for 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1
      piperazinyl)benzimidazole, a novel 5-HT3 receptor antagonist.
AB  - An enzyme immunoassay (EIA) has been developed for determination of 6-amino-5
      chloro-1-isopropyl-2-(4-methyl-1-piperazinyl) benzimidazole (KB-6806), a novel 5
      HT3 receptor antagonist. Anti-KB-6806 antiserum was elicited against the KB-6806
      bovine serum albumin (BSA) conjugate prepared by a diazo coupling reaction
      through the inherent 6-amino group. Beta-galactosidase-labeled 6-amino-5-chloro-1
      isobutyl-2-(4-methyl-1-piperazinyl)benzimidazole was similarly prepared by diazo
      coupling reaction as an enzyme-labeled antigen with a hapten heterologous
      combination of antiserum. The modification at the 4-methyl group of the
      piperazine moiety of KB-6806 significantly decreased the binding affinity to the
      antibody. This method could quantitate KB-6806 in dog plasma in the concentration
      range of 0.078-10 ng/ml with good accuracy and precision. The EIA method has been
      successfully applied to the determination of KB-6806 in plasma after intravenous
      administration of KB-6806 to dogs.

PMID- 11305608
TI  - Possible changes in expression of chemotaxin LECT2 mRNA in mouse liver after
      concanavalin A-induced hepatic injury.
AB  - The functions of leukocyte-derived chemotaxin 2 (LECT2), a novel liver-specific
      protein, are not well defined, especially after hepatic injury. The changes in
      expression of LECT2 mRNA were investigated after concanavalin A (Con A)-induced
      hepatic injury in mice. Serum glutamate pyruvate transaminase (s-GPT) activity
      and the percentage of liver DNA fragmentation, an indicator of hepatic apoptosis,
      increased 8 h after intravenous administration of Con A (13 mg/kg). Expression of
      LECT2 mRNA was reduced from 8-24 h after injection of Con A, but was detected
      again 48 h after recovery from hepatic injury. Expression of tumor necrosis
      factor (TNF)-alpha and interferon (IFN)-gamma mRNA was observed in liver 2 h
      after Con A injection. Z-Val-Ala-Asp(OMe)-CH2F (Z-VAD-FMK), a caspase inhibitor,
      was administered to mice to investigate whether LECT2 was involved in apoptosis
      of liver cells after Con A injection. Z-VAD-FMK inhibited s-GPT activity and DNA
      fragmentation in the liver 8 h after Con A-induced hepatic injury, but did not
      prevent the reduction of LECT2 mRNA, or induction of TNF-alpha and IFN-gamma mRNA
      expression. When the relation between expression of LECT2, TNF-alpha and IFN
      gamma mRNAs was examined 8 h after Con A injection in wild-type or
      immunodeficient (nu-/nu-) mice, the increase in TNF-alpha and IFN-gamma mRNA
      expression was found to be closely related to a reduction in LECT2 mRNA
      expression. These results suggest that the reduction in expression of LECT2 mRNA
      is not directly involved in apoptosis and may be inversely related to the
      expression of TNF-alpha and/or IFN-gamma mRNA in the injured liver.

PMID- 11305609
TI  - Influence of the light schedule on the toxic interaction between propranolol and
      disopyramide in chick embryos.
AB  - The effect of the light schedule on toxic interactions between propranolol and
      disopyramide were studied in chick embryos. Fertilized eggs of White Leghorns
      were incubated under dark conditions and investigated, on two occasions, under
      light conditions or under dark conditions. Propranolol, with and without
      disopyramide, was injected into the air sac of fertilized eggs on the 16th day of
      incubation. Electrocardiograms (ECGs) were recorded 0 to 60 min after the
      injection. After the injection of propranolol with disopyramide, the heart rate
      was significantly decreased compared with the injection of propranolol alone
      under light conditions. In addition, this toxic interaction between propranolol
      and disopyramide was more severe under dark conditions than under light
      conditions. These findings indicate that manipulation of the light schedule has a
      marked influence on the toxic interaction between propranolol and disopyramide in
      chick embryos.

PMID- 11305610
TI  - Pharmacokinetics of granisetron in adults and children with malignant diseases.
AB  - Granisetron (GRN) is widely used for patients with various cancers who suffer
      from chemotherapy-induced vomiting and nausea. The, pharmacokinetics of GRN has
      not been fully evaluated in such patients, however, and its dosage regimen is
      still controversial. In this study, we determined GRN levels in serum and urine
      from lung cancer patients and children suffering from cancer after intravenous
      infusion. In lung cancer patients, the interindividual variations in t(1/2beta),
      area under the concentration-time curve (AUC), and Vd(beta) were relatively
      smaller than expected from previous reports on healthy subjects, while t(1/2beta)
      was prolonged more than 5-fold in healthy subjects. Urinary excretion of
      unchanged GRN in lung cancer patients was ca. 15% of dose, consistent with
      previous reports, and one individual demonstrated an even higher urinary
      excretion (ca. 45%). The pharmacokinetic parameters of GRN in child cancer
      patients varied markedly among individuals, and some child patients had smaller
      t(1/2beta) than adult patients. In these cases, GRN should be administered at
      shorter intervals. These results suggested that a pharmacokinetic study of GRN
      was necessary for planning a dosage regimen and managing chemotherapy-induced
      vomiting and nausea.

PMID- 11305611
TI  - Pharmacokinetics of nimustine, cytosine arabinoside, and methotrexate in
      cerebrospinal fluid during cerebrospinal fluid perfusion chemotherapy.
AB  - This report investigates the pharmacokinetics of nimustine (ACNU), cytosine
      arabinoside (Ara-C), and methotrexate (MTX) in cerebrospinal fluid (CSF) during
      CSF perfusion chemotherapy. A 47-year-old Japanese man with spinal cord,
      cerebellum and brain stem dissemination of oligo-astrocytoma received nine
      courses of CSF perfusion chemotherapy with ACNU, Ara-C, and MTX. A CSF perfusion
      chemotherapy solution was perfused via an Ommaya reservoir in the ventricle, and
      was discharged by drainage though another Ommaya reservoir in the lumbar spinal
      canal. CSF samples via Ommaya reservoirs in the lumbar spinal canal were obtained
      during the fifth and eighth courses of treatment. The concentrations of ACNU and
      Ara-C in CSF were measured by HPLC, and the MTX concentrations by fluorescence
      polarization immunoassay. In the fifth course of treatment, a CSF injection
      chemotherapy solution, consisting of 5 mg of ACNU dissolved in 20 ml of
      artificial CSF, was injected over a few minutes using the Ommaya reservoir. Next,
      a CSF perfusion chemotherapy solution, consisting of 10 mg of Ara-C and 5 mg of
      MTX dissolved in 100 ml of artificial CSF, was perfused over 2 h. In the eighth
      course of treatment, a CSF perfusion chemotherapy solution, consisting of 5 mg of
      ACNU, 10 mg of Ara-C and 5 mg of MTX dissolved in 100 ml of artificial CSF, was
      perfused over 2 h. In both treatments, the highest concentrations of Ara-C and
      MTX in CSF were observed 1 or 2 h after the end of perfusion, with the values of
      each drug being similar. The CSF AUCs of Ara-C and MTX in each treatment were of
      similar values. Although the highest concentration of ACNU in CSF was observed in
      the fifth treatment 1 h after injection (an injection chemotherapy of ACNU plus a
      perfusion chemotherapy of Ara-C and MTX), the concentration of ACNU in CSF was
      undetectable in the eighth treatment (a perfusion chemotherapy of ACNU, Ara-C and
      MTX). We were successful in administering all anticancer drugs, and reaching a
      level of over 1.0 microg/ml concentration in CSF of the lumbar spinal canal,
      using an injection chemotherapy of ACNU plus a perfusion chemotherapy of Ara-C
      and MTX; this was done even though the drugs, in particular ACNU, underwent some
      perfusion-period dependent decomposition.

PMID- 11305612
TI  - Species difference in correlation between in vivo/in vitro liposome-complement
      interactions.
AB  - The objective of this study was to investigate the correlation between in vitro
      and in vivo liposome-complement interactions. Third component of the complement
      (C3) fragments associated with hydrogenated egg phosphatidylcholine (HEPC)-based
      liposomes in vivo and complement-dependent destabilization in vitro were
      determined as an indication of liposome-complement interaction in vivo and in
      vitro, respectively. C3 fragments on the liposomes were detected in both rats and
      guinea pigs. Pretreatment with K76COOH (K76), a complement inactivating agent,
      reduced the binding of C3 fragments. These findings indicated that the liposomes
      remarkably activated the complement system in both animals in vivo.
      Interestingly, significant complement-dependent liposome destabilization was
      observed in rat serum, but not in guinea pig serum, indicating that the liposomes
      activated the complement system in rats, but not in guinea pigs in vitro. Taken
      together, it is apparent that in vitro complement activation by the liposomes is
      not in agreement with in vivo complement activation in ginea pigs. This
      discrepancy in the liposome-complement interaction would suggest the need for
      further investigation to utilize the information obtained from the liposome
      complement interaction to predict in vivo behavior of the liposomes.

PMID- 11305613
TI  - MR imaging of the anterior cruciate ligament: value of thin slice direct oblique
      coronal technique.
AB  - PURPOSE: The value of the thin slice direct oblique coronal technique, which is
      parallel to the anterior cruciate ligament (ACL), was assessed in the evaluation
      of ACL injury in comparison with conventional oblique sagittal and coronal
      images. MATERIAL AND METHODS: A thin slice direct oblique coronal technique was
      developed and applied clinically to 62 patients after conventional oblique
      sagittal and coronal images had been obtained. MR images of these 62 patients (24
      with tears and 38 without tears) with an arthroscopic correlation were evaluated
      by three radiologists who were unaware of the arthroscopic results. The
      diagnostic accuracy of these new images was compared with that of oblique
      sagittal and coronal images by ROC analysis. RESULTS: Conventional oblique
      sagittal and coronal images for the diagnosis of ACL tears revealed accuracies of
      82%, 84%, and 84%, sensitivities of 92%, 92%, and 96% and specificities of 76%,
      79%, and 76% for the three reviewers, respectively. On thin slice direct oblique
      coronal images, specificities of 97%, 97%, and 97%, sensitivities of 96%, 96%,
      and 96%, and accuracies of 97%, 97%, and 97% were obtained, respectively.
      Diagnostic ability was significantly better with direct oblique coronal images
      (mean area under the ROC curve [Az]=0.99) than with conventional oblique sagittal
      and coronal images (Az=0.91) (p<0.05). CONCLUSION: The addition of thin slice
      direct oblique coronal images significantly improved specificity and accuracy in
      the diagnosis of ACL tears.

PMID- 11305614
TI  - Radiographic features of invasive lobular carcinoma of the breast.
AB  - PURPOSE: To evaluate the radiographic features of invasive lobular carcinoma of
      the breast. METHODS: We evaluated the radiographic features of 61 cases of
      histopathologically documented invasive lobular carcinoma. Mammography was
      performed in all cases. In seven of 61 cases, helical CT with contrast medium was
      also carried out. Mammographic findings were analyzed to determine true-positive
      and false-negative rates for the detection of neoplasm. Further, the diameter of
      the tumor as determined on mammography and helical CT was noted for comparison
      with the pathologic size. RESULTS: Mammographic features were divided into six
      types: spiculated mass (38%), indistinct mass (5%), obscured mass (23%),
      asymmetric opacity (16%), architectural distortion (16%), and no findings (2%).
      Microcalcifications were present in 12 cases (20%). The overall sensitivity rate
      was 59%. However, 20 (56%) of 36 cases that were diagnosed as detectable on
      mammography were underestimated in terms of tumor size compared with the
      histopathologic findings. Four cases examined by helical CT with contrast medium
      were compared with the histopathologic findings in terms of extent of the lesion.
      In three cases, helical CT was more precise than mammography, but the
      histopathologic findings showed lesions beyond the region evaluated by helical
      CT. CONCLUSION: Invasive lobular carcinoma is difficult to detect
      radiographically, and the extent of the lesion tends to be underestimated.

PMID- 11305615
TI  - Sensitizing effect of the phosphatidylinositol 3-kinase inhibitor wortmannin on
      thermal neutron irradiation with or without boron compound.
AB  - Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to be an
      efficient radiosensitizer. We have investigated the radiosensitizing effect of
      wortmannin on cell killing against thermal neutrons produced by the Kyoto
      University Research (KUR) reactor. Wortmannin was added to cells 2 hours before
      irradiation and removed 16 hours after irradiation. Cells were irradiated by
      thermal neutrons with or without boron at 0, 10, and 20 ppm. The biological end
      point of cell survival was measured by colony formation assay. The D0 values of
      thermal neutrons in different boron concentrations, 0, 10, and 20 ppm were 1.2,
      1.1, and 1.0 Gy, respectively. When cells were treated with wortmannin, the D0
      values decreased to 0.5, 0.6, and 0.8 Gy at boron concentrations of 0, 10, and 20
      ppm, respectively. Wortmannin enhanced cell death against thermal neutron
      irradiation especially in the absence of boron. Thus, our results suggest that
      wortmannin may be useful to combine with boron neutron capture therapy (BNCT)
      treatment when boron uptake by cells is limited.

PMID- 11305616
TI  - A case of right-sided aortic arch with isolation of the left subclavian artery:
      CT findings.
AB  - We report a case of right-sided aortic arch with isolation of the left subclavian
      artery diagnosed using computed tomography (CT). This was a rare type in which
      the left subclavian artery, originating from the pulmonary artery via the
      arterial duct, was isolated after closure of the ductus. Collateral circulation
      was considered to be obtained mainly from the left intercostal artery via the
      costocervical trunk through the supreme intercostal artery.

PMID- 11305617
TI  - Symptomatic child case of subependymoma in the fourth ventricle without
      hydrocephalus.
AB  - We report a rare child case of symptomatic subependymoma in the fourth ventricle
      without hydrocephalus. The upper half of the tumor was demonstrated as a non
      enhancing isodense mass with punctate calcification on CT, whereas the lower
      portion showed slightly irregular ring-like enhancement with a central hypodense
      area. The tumor was heterogeneously hyperintense on T2-weighted magnetic
      resonance (MR) images. When scanned with a T1-weighted sequence, the upper
      portion of the tumor was isointense to brain, but the lower portion was
      hypointense. However, using Gd-enhanced T1-weighted imaging, such as in
      postcontrast CT, the upper portion did not enhance, whereas the lower portion
      revealed similar ring-like enhancement, which was suggestive of necrosis. To
      further confirm the nature of the tumor, a diffusion-weighted imaging study with
      echo-planar technique was performed, and it indicated the solid nature of the
      tumor, which was confirmed histopathologically.

PMID- 11305618
TI  - Thyroid metastasis from hepatocellular carcinoma as an initial presentation: a
      case report.
AB  - Although metastases to the thyroid are not uncommon at autopsy, most of these
      lesions are clinically occult. To our knowledge, this is the first report of a
      case of hepatocellular carcinoma initially presenting as a thyroid mass. Various
      radiological studies suggested malignant thyroid tumor, and core needle biopsy
      was performed. Metastasis from hepatocellular carcinoma was histopathologically
      suspected, and subsequent abdominal CT revealed advanced hepatocellular
      carcinoma.

PMID- 11305619
TI  - MR imaging of synovial sarcoma arising from the floor of the mouth: a case
      report.
AB  - A previously unreported synovial sarcoma arising from the floor of the mouth
      occurred in a 46-year-old man. Preoperative MR imaging findings of the tumor
      reflected the macroscopic findings of the resected mass. MR imaging findings were
      helpful in the diagnosis of this malignancy.

PMID- 11305620
TI  - CT arteriographic confirmation of focal hepatic fatty infiltration adjacent to
      the falciform ligament associated with drainage of inferior vein of Sappey: a
      case report.
AB  - We experienced a case of focal fatty infiltration in the anteromedial edge of the
      medial segment of the liver adjacent to the falciform ligament associated with
      advanced esophageal cancer. By using CT during selective right internal thoracic
      arteriography, we confirmed that the inferior vein of Sappey drained into the
      area of focal fatty infiltration. This is the first case to directly establish
      the relationship between drainage of the inferior vein of Sappey and occurrence
      of focal fatty infiltration of the liver.

PMID- 11305621
TI  - Choriocarcinoma of the ovary associated with mucinous cystadenoma.
AB  - We report choriocarcinoma of the ovary associated with mucinous cystadenoma in a
      54-year-old postmenopausal woman, the first reported case of this condition.
      Doppler ultrasonography, computed tomography, and magnetic resonance imaging
      showed hypervascularity of the tumor that corresponded to the area of
      choriocarcinoma within the multilocular cyst. The patient exhibited multiple
      pulmonary metastases and died of intracerebral hemorrhage.

PMID- 11305622
TI  - Changes in performance status of elderly patients after radiotherapy.
AB  - BACKGROUND: To examine the feasibility of external radiation therapy for patients
      80 years old and older. METHODS: We analyzed changes in the performance status
      (PS) of 1353 patients by external radiotherapy at Osaka Teishin Hospital. In
      addition, factors influencing PS change and interruption of treatment were
      assessed in patients undergoing radical and palliative radiotherapy. RESULTS:
      Among elderly patients aged 80 years or more (n=67), two patients showed
      deterioration in PS (3%), whereas 128 (10%) did so among those 79 years old or
      younger. The rate of treatment completion was 90% (60/67) for patients aged 80
      years and over compared with 89% (1146/1286) for younger patients. Changes in PS
      were more frequent for palliative treatment (improvement 83/683, 12%;
      deterioration 77/683, 11%) than for radical treatment (improvement 12/305, 4%;
      deterioration 21/305, 7%) because patients with better performance status and
      early disease stages underwent radical treatment. For radical radiotherapy,
      patients with advanced disease (stages III and IV) showed more changes
      (improvement 4/108, 4%; deterioration 17/108, 16%) than those with early ones
      (stages I and II)(improvement 7/132, 5%; deterioration 3/132, 2%) (p<0.01).
      Better treatment results showed a higher treatment completion rate (CR 99%, PR
      86%) than poor treatment results (NC 75%, PD 50%)(p<0.01). For palliative
      therapy, better performance status (PS 0-2) showed a better correlation with
      completion of treatment (403/451 or 89%) than did poor performance status (PS 3
      4)(174/ 232, 75%)(p<0.01). CONCLUSIONS: Age is not a limiting factor for external
      radiation therapy. Poor performance status is a significant predisposing factor
      for interruption of palliative radiotherapy.

PMID- 11305623
TI  - A preliminary open label dose comparison using an antioxidant regimen to
      determine the effect on viral load and oxidative stress in men with HIV/AIDS.
AB  - OBJECTIVE: To investigate the effect of antioxidant supplementation on viral load
      and the antioxidant/reactive oxygen species system in people with HIV. DESIGN:
      Single centre, prospective, dose comparison study. SETTING: Outpatient clinic
      specializing in HIV care. SUBJECTS: Sixty-six participants were sequentially
      recruited by advertisement, and 48 subjects completed the study. INTERVENTIONS: A
      recommended dose antioxidant regimen (5,450 IU vitamin A as beta-carotene, 250 mg
      vitamin C, 100 IU vitamin E, 100 microg selenium, 50 mg coenzyme Q10) or a high
      dose antioxidant regimen (21,800 IU vitamin A as beta-carotene, 1,000 mg vitamin
      C, 400 IU vitamin E, 200 microg selenium, 200 mg coenzyme Q10) for a 12 week
      period. RESULTS: Using repeated measures analysis of variance, the changes over
      treatment time were significant for selenium, glutathione, glutathione peroxidase
      and lipid peroxides (P < 0.03). Changes in allantoin, uric acid and viral load
      were not significant (P > 0.05). The main effects for group and the interaction
      effects were not significant for any of the parameters measured (P > or = 0.05).
      CONCLUSION: Antioxidant supplementation significantly improved some measures of
      oxidative defence. There was no benefit in using a high-dose supplement in this
      study.

PMID- 11305624
TI  - Lipophilic antioxidants and polyunsaturated fatty acids in lipoprotein classes:
      distribution and interaction.
AB  - OBJECTIVE: To study the lipoprotein distribution of supplemented coenzyme Q10
      (CoQ10), vitamin E, and polyunsaturated fatty acids (PUFA). DESIGN: Balanced
      three-period crossover study. SETTING: University research unit. SUBJECTS:
      Eighteen apparently healthy free-living non-smoking volunteers (nine women, nine
      men), mean age 26 +/- 3 y, recruited among the university students; no dropouts.
      INTERVENTIONS: Three supplementation periods of 10 days: 100 mg/day CoQ10, 350
      mg/day D-alpha-tocopherol, and 2 g/day concentrated fish oil. Fasting venous
      blood samples were collected twice before the first period and then after each
      period. Plasma and isolated lipoproteins were analysed for cholesterol,
      triacylglycerol, alpha- and gamma-tocopherol, CoQ10, and fatty acid composition.
      RESULTS: Significant (P < 0.05) increase in CoQ10 and alpha-tocopherol occurred
      in all lipoprotein classes after supplementation. CoQ10 was primarily
      incorporated into low-density lipoprotein (LDL). alpha-tocopherol and fish oil n
      3 PUFAs had similar patterns. They were equally distributed between LDL and high
      density lipoprotein (HDL), with a smaller part in VLDL. The total sum of PUFA was
      unchanged following all supplementations, but fish oil increased the amount of n
      3 fatty acids at the expense of n-6 fatty acids. CONCLUSION: Lipoprotein
      distribution of CoQ10 is markedly different from that of alpha-tocopherol,
      suggesting that they may be metabolised by distinct routes. alpha-Tocopherol is
      distributed similarly to n-3 fatty acids, thus providing protection on location
      for the oxidatively labile PUFAs.

PMID- 11305625
TI  - Validation of food diary method for assessment of dietary energy and
      macronutrient intake in infants and children aged 6-24 months.
AB  - OBJECTIVES: To compare the estimated food diary record (ED) method against
      weighed intake record method (WI) for assessing dietary intake in infants and
      children aged 6-24 months; additionally, to compare WI with metabolisable energy
      intake (ME) measured by doubly labelled water (DLW) in infants aged 6 12 months.
      DESIGN: Cross-over study of 5 day WI vs 5 day ED. SUBJECTS: Seventy-two children
      aged 6-24 months. METHODS: Subjects were randomly assigned to one method during
      week 1 crossing over to the alternative method in week 2. Data were coded and
      translated into daily nutrient intakes using COMP-EAT version 5 nutritional
      analysis software. The analysis compared energy, protein, fat and carbohydrate.
      Twenty-one infants were dosed with DLW for measurement of total energy
      expenditure (TEE) and ME. RESULTS: Mean energy intake calculated from WI and ED
      was 3,782 and 3,920 kJ/day, respectively. There was no significant difference
      between these values. Using WI as a reference, ED showed a mean bias of 138
      kJ/day, equivalent to 3.6% of mean energy intake. Limits of agreement (+/- 2 s.d.
      of the bias) were wide at +/- 1,385 kJ/day. There were no significant differences
      between methods for any of the nutrient sub-classes. Using DLW as a reference, WI
      showed a mean bias of 243 kJ/day, equivalent to 7.3% of mean energy intake,
      limits of agreement were wide at +/- 1686 kJ/day. CONCLUSION: There is no
      evidence from the present analysis that ED is less accurate than WI for assessing
      energy and nutrient sub-class intakes in groups of this age but this good
      agreement between methods in groups does not extend to individuals.

PMID- 11305626
TI  - Dietary habits during adolescence--results of the Belgian Adolux Study.
AB  - OBJECTIVE OF THE PRESENT STUDY: To analyse the usual dietary habits of Belgian
      adolescents from a high cardiovascular risk population. METHODS: A food frequency
      questionnaire (57 items) was administered to the whole sample. Complementary
      questions specified some types of food (eg fat content). A subgroup of 234
      adolescents gave detailed information on portion size (picture book and food
      samples). SETTING: Twenty-four secondary schools in the Belgian province of
      Luxembourg. SUBJECTS: A total of 1,526 adolescents (12-17y) selected by a
      multiclustered stage sampling (participation: 83.6%). RESULTS: Respectively 46%
      and 60% of the adolescents did not eat fruit and vegetables daily. Most of the
      adolescents (72%) consumed at least one dairy product daily. The frequent
      consumption of chocolate and French fries indicated the strong cultural influence
      on dietary habits while imported foods (like hamburgers) had little success. One
      third of the adolescents (33%, n = 509) drank alcohol at least once a week and
      this proportion rose to 57% in the oldest age group. Boys and girls differed
      significantly in their diet, with girls choosing healthier foods. Dietary habits,
      in particular drinking habits, differed also significantly between education
      levels, assessed by the learning option of the participants. The semi
      quantitative questionnaire showed that two-thirds of the adolescents had a lipid
      intake (mainly saturated fatty acids) which exceeded 35% of the total caloric
      intake. Complex carbohydrates represented less than half of the total
      carbohydrates intake. CONCLUSION: The study of the diet of Belgian adolescents
      confirmed the strong influence of tradition, in particular on the consumption of
      high fat content foods. The promotion of healthy diet in adolescents should
      consider the cultural influence, even for this young age group.

PMID- 11305627
TI  - Reduced mortality among whole grain bread eaters in men and women in the
      Norwegian County Study.
AB  - OBJECTIVE: To study whether mortality is reduced among whole grain eaters in
      Norway. DESIGN: Non-interventional, prospective, baseline 1977-1983, followed for
      mortality through to 1994. SETTING: Three Norwegian counties. SUBJECTS: A total
      of 16,933 men and 16,915 women; systematic screening of all residents aged 35-56y
      at baseline, not disabled and free of cardiovascular disease (79% response rate).
      PREDICTOR VARIABLE: We combined self-report of type and number of bread slices
      (white, light whole grain, dense whole grain) to form a whole grain bread score,
      with range 0.05 (1 slice per day, made with 5% whole grain flour) to 5.4 (9
      slices per day, made with 60% whole grain flour). RESULTS: Norwegian whole grain
      bread eaters were less likely to be smokers, were more physically active, had
      lower serum cholesterol and systolic blood pressure, and ate less total and
      saturated fat as a proportion of energy intake than white bread eaters. After
      adjustment for age, energy intake, sex, serum cholesterol, systolic blood
      pressure, smoking, body mass index, physical activity at leisure and work, and
      use of cod liver oil or other vitamin supplements, hazard rate ratios (HRR) for
      total mortality were inverse and graded across whole grain bread score categories
      (category 5 vs category 1 HRR: 0.75, 95% confidence interval 0.63-0.89 in men and
      0.66, 0.44-0.98 in women). CONCLUSION: Protection by whole grain intake against
      chronic disease is suggested in Norway, where four times as much whole grain is
      consumed as in the United States.

PMID- 11305628
TI  - Multi-component body composition models: recent advances and future directions.
AB  - OBJECTIVE: This overview examines concepts related to a category of body
      composition methods generally referred to as multi-component models, that is,
      those models that include three or more components. We summarize the rationale
      for, applications, and types of multi-component models along with sources of
      error. Our review presents the strengths and limitations of available models and
      identifies important future research directions.

PMID- 11305629
TI  - Catechin intake and associated dietary and lifestyle factors in a representative
      sample of Dutch men and women.
AB  - OBJECTIVE: To study the intake of catechins in the Dutch population and to assess
      the relation between catechin intake and other dietary factors. Catechins,
      dietary components that belong to the flavonoid family, potentially protect
      against chronic diseases such as cancer and cardiovascular diseases. Catechins
      are the major components of tea, but they are present in many other plant foods
      as well. DESIGN: Data were used from a nationwide dietary survey carried out in
      1998 among a representative sample of 6200 Dutch men and women aged 1-97y.
      Dietary data were collected using a 2 day dietary record method. RESULTS: The
      average daily catechin intake was 50 mg (s.d. 56 mg/day). Catechin intake
      increased with age, and the intake was higher in women (60 mg/day) than in men
      (40 mg/day). Tea was the main catechin source in all age groups, whereas
      chocolate was second in children, and apples and pears were second in adults and
      elderly. Catechin intake was lower in smokers than in non-smokers, and increased
      with socio-economic status. A high intake was associated with a high intake of
      fiber (r = 0.20), vitamin C (r = 0.17) and beta-carotene (r = 0.10). CONCLUSIONS:
      Catechins are quantitatively important bioactive components of the daily diet,
      which should be taken into account when studying the relation between diet and
      chronic diseases. Catechin intake is only moderately associated with the intake
      of other nutrients, but much stronger with certain health behaviours such as
      smoking.

PMID- 11305630
TI  - Five decades of trends in anemia in Israeli infants: implications for food
      fortification policy.
AB  - OBJECTIVE: To describe the secular trends in the prevalence rates of iron
      deficiency anemia (IDA) in infants in Israel, identify population group
      differences and assess the effectiveness of the 1985 Public Health directives on
      iron supplementation and avoidance of cow's milk in the first year of life.
      DESIGN: A systematic analysis of published and unpublished cross-sectional
      studies. METHODS: IDA rates in 1-y-old infants between 1946 and 1997 were
      assessed from published papers and reports. Rates for Arab infants were available
      from 1984. Data on routine hemoglobin tests on 1-y-old infants for Arabs and Jews
      separately were obtained from four health districts for the period 1987 to 1997.
      Analyses were done for the periods prior to and following the Public Health
      directives. RESULTS: The prevalence of IDA in Jewish infants declined from 68% in
      1946 to 50% in 1985 at an average annual rate of -1.43%. Following the iron
      supplementation directives, the average annual rate of decline increased to -4.0%
      and reached a prevalence of about 11% in 1996. IDA rates in Arab infants declined
      by an annual average of -3.7%, and were consistently almost twice as high as for
      Jewish infants. CONCLUSIONS: Despite the contribution of the iron supplementation
      program to the reduction in TDA, the persistently high rates indicate inadequate
      iron content in the diet. This emphasizes the important role of a national food
      fortification program, using staple foods commonly consumed.

PMID- 11305631
TI  - A stearic acid-rich diet improves thrombogenic and atherogenic risk factor
      profiles in healthy males.
AB  - OBJECTIVE: To determine whether healthy males who consumed increased amounts of
      dietary stearic acid compared with increased dietary palmitic acid exhibited any
      changes in their platelet aggregability, platelet fatty acid profiles, platelet
      morphology, or haemostatic factors. DESIGN: A randomized cross-over dietary
      intervention. SUBJECTS AND INTERVENTIONS: Thirteen free-living healthy males
      consumed two experimental diets for 4 weeks with a 7 week washout between the two
      dietary periods. The diets consisted of approximately 30% of energy as fat (66%
      of which was the treatment fat) providing approximately 6.6% of energy as stearic
      acid (diet S) or approximately 7.8% of energy as palmitic acid (diet P). On days
      0 and 28 of each dietary period, blood samples were collected and anthropometric
      and physiological measurements were recorded. RESULTS: Stearic acid was increased
      significantly in platelet phospholipids on diet S (by 22%), while on diet P
      palmitic acid levels in platelet phospholipids also increased significantly (8%).
      Mean platelet volume, coagulation factor FVII activity and plasma lipid
      concentrations were significantly decreased on diet S, while platelet aggregation
      was significantly increased on diet P. CONCLUSION: Results from this study
      indicate that stearic acid (19g/day) in the diet has beneficial effects on
      thrombogenic and atherogenic risk factors in males. The food industry might wish
      to consider the enrichment of foods with stearic acid in place of palmitic acid
      and trans fatty acids.

PMID- 11305635
TI  - Application of directly coupled HPLC NMR to separation and characterization of
      lipoproteins from human serum.
AB  - Disorders in lipoprotein metabolism are critical in the etiology of several
      disease states such as coronary heart disease and atherosclerosis. Thus, there is
      considerable interest in the development of novel methods for the analysis of
      lipoprotein complexes. We report here a simple chromatographic method for the
      separation of high-density lipoprotein, low-density lipoprotein, and very low
      density lipoprotein from intact serum or plasma. The separation was achieved
      using a hydroxyapatite column and elution with pH 7.4 phosphate buffer with 100
      microL injections of whole plasma. Coelution of HDL with plasma proteins such as
      albumin occurred, and this clearly limits quantitation of that species by HPLC
      peak integration. We also show, for the first time, the application of directly
      coupled HPLC 1H NMR spectroscopy to confirm the identification of the three major
      lipoproteins. The full chromatographic run time was 90 min with stopped-flow 600
      MHz NMR spectra of each lipoprotein being collected using 128 scans, in 7 min.
      The 1H NMR chemical shifts of lipid signals were identical to conventional NMR
      spectra of freshly prepared lipoprotein standards, confirming that the
      lipoproteins were not degraded by the HPLC separation and that their gross
      supramolecular organization was intact.

PMID- 11305632
TI  - The realization of a project aimed at reducing the plasmatic lipid level in a
      large Italian population improves the mean calcium daily intake: the Brisighella
      Study.
AB  - OBJECTIVES: Evaluation of the impact of a coronary heart disease prevention
      program on calcium, magnesium, phosphorus and vitamin D dietary intake in respect
      of recommended daily allowances in a large Italian rural population. DESIGN:
      Retrospective analysis of the Brisighella Study dietary data. The Brisighella
      Study started in 1972 as a longitudinal study on atherosclerosis risk factors.
      SETTING: Brisighella, a rural North Italian village. SUBJECTS: The Brisighella
      population's dietary habits were monitored from 1980 every 4 h through a dietary
      record sheet. 1,350 constantly tested subjects were subdivided according to NHI
      Consensus Conference on Calcium RDA. INTERVENTION: In 1986, the studied subjects
      were invited to reduce their consumption of animal fats and cholesterol through a
      Nutrition Educational Program (NEP). RESULTS: Before NEP, calcium intake was low
      in each sex and age category: 20-40% of the populatioin had a daily intake < 550
      mg. In 1988, among the 1350 subjects who constantly completed the questionnaire
      (M = 651, F = 699), the mean calcium intake significantly rose in all age
      categories: M = 1,003 (25-65 y) and 877 ( > 65) mg/24h (P < 0.001 vs 1984); F =
      923 (25-50), 860 (51-65) and 767 (> 65)mg/24h (P < 0.05). In 1992, 3y after the
      NEP conclusion, calcium intake dropped in each sex and age category. The NEP
      influenced vitamin D, phosphorus and magnesium intakes less. CONCLUSIONS: A
      collective NEP aimed at lowering saturated fats and cholesterol intakes, improves
      the calcium intake; in order to maintain their efficacy on nutritional habit
      changes, these programs must become an ongoing item.

PMID- 11305636
TI  - Real-time dynamics of single-DNA molecules undergoing adsorption and desorption
      at liquid-solid interfaces.
AB  - The conformational dynamics and adsorption/desorption behavior of individual
      lambda-DNA molecules at liquid-solid interfaces were monitored by imaging within
      the evanescent field layer using total internal reflection fluorescence
      microscopy. At a fused-silica surface, molecular conformation and adsorption
      behavior were found to depend on both pH and buffer composition. A histogram of
      individual lambda-DNA adsorption durations measured by hydrodynamically flowing
      molecules along the interface exhibited asymmetry nearly identical to that of the
      corresponding elution peaks found in capillary liquid chromatography and
      capillary electrophoresis. The accessibility of the surface to the molecules,
      which is proportional to the capillary surface area-to-volume ratio, can be
      correlated with the capacity factor and the relative adsorption factor. At a C18
      surface, the dynamics of individual DNA molecules changed with the addition of
      organic solvent as well as with pH. Hydrophobic interaction rather than
      electrostatic interaction was the major driving force for adsorption of
      individual DNA molecules.

PMID- 11305637
TI  - Statistical analysis of single-molecule colocalization assays.
AB  - In chemical assays, specific molecular recognition events result in close
      physical proximity of two molecular species, e.g., ligands and receptors.
      Microscopy techniques that are able to image individual molecules allow for
      achieving a positional accuracy far beyond the resolution limit Therefore,
      independent position determination, e.g., by dual-color microscopy, becomes
      possible, permitting determination of intermolecular distances beyond the
      resolution limit. Nonzero measured distances occur due to experimental
      inaccuracies in case of a recognition event or due to accidental close proximity
      between ligand-receptor pairs. Using general statistical considerations, finite
      measured distances between single ligand-receptor pairs are directly translated
      into probabilities for true molecular recognition or mere accidental proximity.
      This enables a quantitative statistical analysis of single recognition events. It
      is demonstrated that in a general assay, even in the presence of strong
      unspecific background, the probability for a certain diagnosis and a measure for
      its reliability can be extracted from the observation of a few binding events.
      The power of the method is demonstrated at the example of a single-molecule DNA
      hybridization assay. Our findings are of major importance for future assay
      miniaturization and assaying with minute amounts of analyte.

PMID- 11305641
TI  - On-line analysis of nitrogen stable isotopes in NO from ambient air samples.
AB  - A method was developed for the on-line analysis of nitrogen stable isotopes at
      the natural abundance level in NO in order to study the NO contribution to the
      nitrogen cycle in ecosystems and in the atmosphere. The method enables a quick
      and accurate determination of 15N/14N ratios for NO and consists of the following
      steps: (a) accumulation of NO from air samples on a molecular sieve of 5 A, (b)
      desorption of NO from the molecular sieve during 15 min of heating at 350 degrees
      C (an offset of Deltadelta 4.6% must be corrected for), (c) trapping and
      cryofocusation of the desorbed NO on a PoraPlot Q matrix at -196 degrees C during
      heating, (d) release of the trapped NO from the PoraPlot Q matrix followed by
      chromatographic separation, reduction to N2, and isotopic composition analysis. A
      minimum sample size of 125 nmol of NO is recommended. A correction function for
      the calculation of the delta15N-NO values was introduced for sample sizes from
      125 to 220 nmol of NO. Measurements of NO in automobile exhaust have proven the
      applicability of the developed method.

PMID- 11305642
TI  - A genetically engineered fusion protein with  horseradish peroxidase as a marker
      enzyme for use in competitive immunoassays.
AB  - Horseradish peroxidase is one of the most widely used marker enzymes in
      immunoassays. Several disadvantages are encountered upon chemical conjugation of
      peroxidase with antibodies or antigens, as are low reproducibility and undefined
      stoichiometry. We here describe for the first time the production of a
      recombinant fusion of a protein analyte with horseradish peroxidase in
      Escherichia coli, employing refolding of inclusion bodies and reconstitution with
      heme. The genetic fusion approach enables preparation of conjugates with 1:1
      stoichiometry and defined structure. As a protein analyte, the human heart fatty
      acid binding protein (H-FABP) was chosen, which is a new and sensitive marker for
      acute myocardial infarction. The recombinant conjugate was fully active [650 U/mg
      with 2,2-azino-bis(3-ethyl-thiazoline-6-sulfonate) as substrate] and obtained in
      a yield of 12 mg/L of E. coli culture, which is better than that for recombinant
      peroxidase alone. The competitive immunoassay that was developed with the
      recombinant conjugate requires fewer incubation steps than the traditional
      sandwich ELISA format. It permitted the detection of H-FABP directly in plasma in
      the range of 10-1500 ng/mL which is the relevant range for clinical decision
      making.

PMID- 11305646
TI  - Layer-by-layer self-assembly of glucose oxidase and Os(Bpy)2CIPyCH2NH
      poly(allylamine) bioelectrode.
AB  - The uptake of glucose oxidase (GOx) onto a polycationic redox polymer (PAA-Os)
      modified surface, by adsorption from dilute aqueous GOx solutions, was followed
      by the quartz crystal microbalance (QCM) and shows double exponential kinetics.
      The electrochemistry of the layer-by-layer-deposited redox-active polymer was
      followed by cyclic voltammetry in glucose-free solutions, and the enzyme
      catalysis mediated by the redox polymer was studied in beta-D-glucose-containing
      solutions. AFM studies of the different layers showed the existence of large two
      dimension enzyme aggregates on the osmium polymer for 1 microM GOx and less
      aggregation for 50 nM GOx solutions. When the short alkanethiol, 2,2'
      diaminoethyldisulfide was preadsorbed onto gold, a monoexponential adsorption law
      was observed, and single GOx enzyme molecules could be seen on the surface where
      the enzyme was adsorbed from 50 nM GOx in water.

PMID- 11305648
TI  - Detection of viable oocysts of Cryptosporidium parvum following nucleic acid
      sequence based amplification.
AB  - A reliable method using nucleic acid sequence based amplification (NASBA) with
      subsequent electrochemiluminescent detection for the specific and sensitive
      detection of viable oocysts of Cryptosporidium parvum in environmental samples
      was developed. The target molecule was a 121-nt sequence from the C. parvum heat
      shock protein hsp70 mRNA. Oocysts of C. parvum were isolated from environmental
      water via vortex flow filtration and immunomagnetic separation. A brief heat
      shock was applied to the oocysts and the nucleic acid purified using an optimized
      very simple but efficient nucleic acid extraction method. The nucleic acid was
      amplified in a water bath for 60-90 min with NASBA, an isothermal technique that
      specifically amplifies RNA molecules. Amplified RNA was hybridized with specific
      DNA probes and quantified with an electrochemiluminescence (ECL) detection
      system. We optimized the nucleic acid extraction and purification, the NASBA
      reaction, amplification, and detection probes. We were able to amplify and detect
      as few as 10 mRNA molecules. The NASBA primers as well as the ECL probes were
      highly specific for C. parvum in buffer and in environmental samples. Our
      detection limit was approximately 5 viable oocysts/sample for the assay
      procedure, including nucleic acid extraction, NASBA, and ECL detection. Nonviable
      oocysts were not detected.

PMID- 11305650
TI  - Graphite-teflon composite bienzyme electrodes for the determination of
      cholesterol in reversed micelles. Application to food samples.
AB  - A bienzyme amperometric composite biosensor for the determination of free and
      total cholesterol in food samples is reported. Cholesterol oxidase and
      horseradish peroxidase, together with potassium ferrocyanide as a mediator, are
      incorporated into a graphite-70% Teflon matrix. The compatibility of this
      biosensor design with predominantly nonaqueous media allows the use of reversed
      micelles as working medium. The reversed micelles are formed with ethyl acetate
      as continuous phase (in which cholesterol is soluble), a 4% final concentration
      of 0.05 mol L(-1) phosphate buffer solution, pH 7.4, as dispersed phase, and 0.1
      mol L(-1) AOT as emulsifying agent. Studies on the repeatability of the
      amperometric response obtained at +0.10 V, with and without regeneration of the
      electrode surface by polishing, on the useful lifetime of one single biosensor
      and on the reproducibility in the fabrication of different pellets illustrate the
      robustness of the biosensor design. Determination of free and total cholesterol
      in food samples such as butter, lard, and egg yoke was carried out, and the
      obtained results were advantageously compared with those provided by using a
      commercial Boehringer test kit.

PMID- 11305651
TI  - Simultaneous measurement of dopamine and ascorbate at their physiological levels
      using voltammetric microprobe based on overoxidized poly(1,2-phenylenediamine)
      coated carbon fiber.
AB  - Overoxidized poly-(1,2-phenylenediamine) (OPPD)-coated carbon fiber
      microelectrodes (CFMEs) exhibit, in combination with square-wave voltammetry
      (SWV) detection mode, the attractive ability to simultaneously measure low nM
      dopamine (DA) and mM ascorbate (AA) in a pH 7.4 medium. The PPD polymer film is
      electrodeposited onto a carbon fiber at a constant potential of 0.8 V versus
      Ag/AgCl using a solution containing sodium dodecylsulfate as the dopant. After
      overoxidation using cyclic voltammetry (CV) in the potential range from 0 to 2.2
      V at a scan rate of 10 V/s, the resulting OPPD-CFME displays a high SWV current
      response to cationic DA at approximately 0.2 V and has a favorably low response
      to anionic AA at approximately 0.0 V vs Ag/AgCl. The preparation of the new OPPD
      sensing film has been carefully studied and optimized. The OPPD properties and
      behavior were characterized using CV and SWV under various conditions and are
      discussed with respect to DA and AA detection. The linear calibration range for
      DA in the presence of 0.3 mM AA is 50 nM to 10 microM, with a correlation
      coefficient of 0.998 and a detection limit of 10 nM using 45-s accumulation. The
      detection limit for DA in the absence of AA was estimated to be 2 nM (S/N = 3).
      The linear range for AA in the presence of 100 nM DA is 0.2-2 mM, with a
      correlation coefficient of 0.999 and a detection limit of 80 microM. The
      reproducibilities of SWV measurements at OPPD-CFCMEs are 1.6% and 2.5% for 100 nM
      DA and 0.3 mM AA, respectively. Potential interfering agents, such as 3,4
      dihydroxyphenylacetic acid, uric acid, oxalate, human serum proteins, and
      glucose, at their physiologically relevant or higher concentrations did not have
      any effect. These favorable features offer great promise for in vitro and in vivo
      application of the proposed OPPD-coated microprobe.

PMID- 11305652
TI  - Plant tissue-based chemiluminescence flow biosensor for glycolic acid.
AB  - A novel plant tissue-based chemiluminescence (CL) biosensor for glycolic acid
      combined with flow injection analysis is proposed in this paper. The spinach
      tissue acts as the molecular recognition element. Glycolic acid is oxidized by
      oxygen under the catalysis of glycolate oxidase in the tissue column to produce
      hydrogen peroxide, which can react with luminol in the presence of peroxidase of
      spinach tissue to generate a CL signal. The CL emission intensity was linear with
      glycolic acid concentration in the range of 4 x 10(-3)-4 x 10(-6) mol/L and the
      detection limit was 1.3 x 10(-6) mol/L. The biosensor was stable for about 3
      weeks. A complete analysis, including sampling and washing, could be performed in
      1.5 min with a relative standard deviation of 1.7%.

PMID- 11305653
TI  - Protein sizing on a microchip.
AB  - We have developed a microfabricated analytical device on a glass chip that
      performs a protein sizing assay, by integrating the required separation,
      staining, virtual destaining, and detection steps. To obtain a universal
      noncovalent fluorescent labeling method, we have combined on-chip dye staining
      with a novel electrophoretic dilution step. Denatured protein-sodium dodecyl
      sulfate (SDS) complexes are loaded on a chip and bind a fluorescent dye as the
      separation begins. At the end of the separation channel, an intersection is used
      to dilute the SDS below its critical micelle concentration before the detection
      point. This strongly reduces the background due to dye molecules bound to SDS
      micelles and also increases the peak amplitude by 1 order of magnitude. Both the
      on-chip staining and SDS dilution steps occur in the 100-ms time scale and are
      approximately 10(4) times faster than their conventional counterparts in SDS
      PAGE. This represents a much greater speed increase due to microfabrication than
      has been obtained in other assay steps such as electrophoretic separations. We
      have designed and tested a microchip capable of sequentially analyzing 11
      different samples, with sizing accuracy better than 5% and high sensitivity (30
      nM for carbonic anhydrase).

PMID- 11305654
TI  - Determination of carcinoembryonic antigen in human sera by integrated bead-bed
      immunoassay in a microchip for cancer diagnosis.
AB  - A bead-bed immunoassay system was structured on a microchip and applied to
      determine carcinoembryonic antigen (CEA), which is a commonly used marker of
      colon cancer. Polystyrene beads precoated with anti-CEA antibody were introduced
      into a microchannel, and then a serum sample containing CEA, the first antibody,
      and the second antibody conjugated with colloidal gold were reacted successively.
      The resulting antigen-antibodies complex, fixed on the bead surface, was detected
      using a thermal lens microscope (TLM). A highly selective and sensitive
      determination of an ultratrace amount of CEA in human sera was made possible by a
      sandwich immunoassay system that needs three antibodies for an assay. A detection
      limit dozens of times lower than the conventional ELISA was achieved. Moreover,
      when serum samples for 13 patients were assayed with this system, there was a
      high correlation (r = 0.917) with the conventional ELISA. The integration reduced
      the time necessary for the antigen-antibody reaction to approximately 1%, thus
      shortening the overall analysis time from 45 h to 35 min. Moreover, troublesome
      operations required for conventional heterogeneous immunoassays could be much
      simplified. This microchip-based diagnosis system is the first microchip-based
      system that is practically useful for clinical diagnoses with short analysis
      time, high sensitivity, and easy procedures.

PMID- 11305655
TI  - Differential screening and mass mapping of proteins from premalignant and cancer
      cell lines using nonporous reversed-phase HPLC coupled with mass spectrometric
      analysis.
AB  - Nonporous (NPS) RP-HPLC has been used to rapidly separate proteins from whole
      cell lysates of human breast cell lines. The nonporous separation involves the
      use of hard-sphere silica beads of 1.5-microm diameter coated with C18, which can
      be used to separate proteins ranging from 5 to 90 kDa. Using only 30-40 microg of
      total protein, the protein molecular weights are detectable on-line using an ESI
      oaTOF MS. Of hundreds of proteins detected in this mass range, approxinately 75
      80 are more highly expressed. The molecular weight profiles can be displayed as a
      mass map analogous to a virtual "1-D gel" and differentially expressed proteins
      can be compared by image analysis. The separated proteins can also be detected by
      UV absorption and differentially expressed proteins quantified. The eluting
      proteins can be collected in the liquid phase and the molecular weight and
      peptide maps determined by MALDI-TOF MS for identification. It is demonstrated
      that the expressed protein profiles change during neoplastic progression and that
      many oncoproteins are readily detected. It is also shown that the response of
      premalignant cancer cells to estradiol can be rapidly screened by this method,
      demonstrating significant changes in response to an external agent. Ultimately,
      the proteins can be studied by peptide mapping to search for posttranslational
      modifications of the oncoproteins accompanying progression.

PMID- 11305656
TI  - Screening of ion channel receptor agonists using capillary electrophoresis-patch
      clamp detection with resensitized detector cells.
AB  - Efficient techniques for identifying endogenous and synthetic ligands of ion
      channels are important in understanding neuronal communication and for screening
      drug libraries. This paper describes a technique based on capillary
      electrophoresis (CE) separation coupled to patch-clamp (PC) detection where a
      pulsed-flow superfusion scheme was implemented for improved detection. The
      nicotinic acetylcholine receptor (nAChr) agonists acetylcholine, carbachol, and (
      )-nicotine were fractionated and detected by patch-clamped pheochromcytoma
      detector cells. The high-conductance state of the nAChr during CE-PC detection
      was maintained and repetitively resensitized using pulsed-flow superfusion with
      agonist-free buffer. In this way, each agonist evoked an ensemble of peak
      currents that reflected the spatiotemporal distribution for the ligand at the
      cell surface. The technique takes advantage of the intrinsic high selectivity and
      sensitivity of membrane-expressed receptors and allowed for resolution and
      identification of closely migrating ligands. The method was employed for
      determination of acetylcholine content in cell lysates.

PMID- 11305657
TI  - Two-dimensional direct-reading fluorescence spectrograph for DNA sequencing by
      capillary array electrophoresis.
AB  - We report a compact, two-dimensional direct-reading fluorescence spectrograph and
      demonstrate its application to DNA sequencing by capillary array electrophoresis.
      The detection cuvette is based on sheath flow, wherein the capillaries terminate
      in a two-dimensional array in a fluid-filled chamber that is pressurized with
      buffer. A thin metal plate is located downstream from the capillaries. This
      barrier plate has an array of holes that precisely matches the location of the
      capillaries. Buffer flows through the holes, drawing analyte from the capillaries
      in a well-defined array of thin filaments. Fluorescence is excited in the upper
      chamber with an elliptically shaped laser beam. The bottom chamber is sealed with
      a glass window and drained from the side. Fluorescence is detected by imaging the
      illuminated sample streams through the holes in the barrier plate. A prism is
      used to disperse fluorescence from each sample across a CCD camera so that the
      emission spectrum is monitored simultaneously from each capillary. The instrument
      is demonstrated in a 32-capillary configuration but can be scaled to several
      thousand capillaries.

PMID- 11305659
TI  - High-mass accuracy of product ions produced by SORI-CID using a dual electrospray
      ionization source coupled with FTICR mass spectrometry.
AB  - High-mass accuracy is demonstrated using internal calibration for product ions
      produced by sustained off-resonance irradiation collision-induced dissociation
      (SORI-CID) of a 15-mer oligonucleotide, 5'-(CTG)5-3'. Internal calibration for
      this tandem MS experiment was accomplished using a dual electrospray ionization
      (ESI) source coupled with Fourier transform ion cyclotron resonance mass
      spectrometry (FTICR-MS) utilizing hexapole accumulation and gated trapping. The
      pulse sequence entails injection, trapping, and gas-phase isolation of the
      precursor ion of interest followed by the SORI-CID of this ion and, subsequently,
      injection and trapping of the internal mass calibrant (i.e., poly(ethylene
      glycol) with a 1000 Da average mass). The product ions and the poly(ethylene
      glycol) ions are then simultaneously excited by a broadband frequency chirp
      excitation waveform and detected. This technique corrects for space-charge
      effects on the measurement of an ion's cyclotron frequency experienced when
      externally calibrated data are used. While external calibration for FTICR-MS can
      result in mass errors of greater than 100 ppm, this internal standardization
      method demonstrated significantly more consistent accurate mass measurements with
      average mass errors ranging from -1.2 to -3.2 ppm for the 15-mer oligonucleotide
      used in this study. This method requires limited modifications to ESI-FTICR mass
      spectrometers and is applicable for both positive and negative modes of
      ionization as well as other sample types (e.g., pharmaceuticals, proteins, etc.).

PMID- 11305661
TI  - Mass spectrometric determination of O-glycosylation sites using beta-elimination
      and partial acid hydrolysis.
AB  - The present study demonstrates that treating O-glycosylated peptides with
      methylamine vapor followed by partial acid hydrolysis is an effective means for
      locating O-glycosylation site(s). The reaction with methylamine transforms the
      glycosylated Ser and Thr residues into stable methylamine derivatives with a mass
      increment of +13 Da relative to nonglycosylated Ser and Thr residues. Peptide
      sequencing based on partial acid hydrolysis followed by mass spectrometric
      analysis or in favorable cases by CID-MS/MS enables the determination of the
      formerly O-glycosylated sites.

PMID- 11305662
TI  - Tandem infrared multiphoton dissociation and collisionally activated dissociation
      techniques in a quadrupole ion trap.
AB  - Tandem infrared multiphoton dissociation and collisionally activated dissociation
      methods are implemented in a quadrupole ion trap mass spectrometer and used to
      characterize an array of antibiotic ions generated by electrospray ionization.
      The tandem methods prove useful for probing fragmentation genealogies, evaluating
      the structures of lower mass fragment ions produced from higher mass molecular
      ions, and differentiating isobaric ions. The infrared multiphoton dissociation
      method is more efficient for producing an array of fragment ions over a large
      mass range, whereas collisionally activated dissociation is preferable for the
      analysis of lower m/z ions.

PMID- 11305663
TI  - Identification of bacteriophage MS2 coat protein from E. coli lysates via ion
      trap collisional activation of intact protein ions.
AB  - Collisional activation of the intact MS2 viral capsid protein with subsequent
      ion/ion reactions has been used to identify the presence of this virus in E. coli
      lysates. Tandem ion trap mass spectrometry experiments on the +7, +8, and +9
      charge states, followed by ion/ion reactions, provided the necessary sequence tag
      information (and molecular weight data) needed for protein identification via
      database searching. The most directly informative structural information is
      obtained from those charge states that produce a series of product ions arising
      from fragmentation at adjacent residues. The formation of these product ions via
      dissociation at adjacent amino acid residues depends greatly on the charge state
      of the parent ion. Database searching of the charge-state-specific sequence tags
      was performed by two different search engines: the ProteinInfo program from the
      Protein information Retrieval On-line World Wide Web Lab or PROWL and the
      TagIdent program from the ExPASy molecular biology server. These search engines
      were used in conjunction with the sequence tag information generated via
      collisional activation of the intact viral coat protein. These programs were used
      to evaluate the feasibility of generating sequence tags from collisional
      activation of intact multiply charged protein ions in a quadrupole ion trap.

PMID- 11305664
TI  - Interfacing a polymer-based micromachined device to a nanoelectrospray ionization
      Fourier transform ion cyclotron resonance mass spectrometer.
AB  - Here we report the design, fabrication, and operation of a polymer-based
      microchip device interfaced to a nanoelectrospray ionization source and a Fourier
      transform ion cyclotron resonance mass spectrometer. The poly(methyl
      methacrylate) micromachined device was fabricated using X-ray lithography to
      produce a network of channels with high aspect ratios. Fabrication of high aspect
      ratio channels allows for zero dead volume interfaces between the microchip
      platform and the nanoelectrospray capillary interface. The performance of this
      device was evaluated with standard peptide and protein samples. High-quality mass
      spectral data from peptide and proteins (and mixtures thereof) were obtained
      without any interfering chemical noise from the polymer or the developers and
      plasticizers used in the fabrication process. Sample cross-contamination is not a
      problem using this polymer-based microchip device as demonstrated by the
      sequential analysis of several proteins. The nanoelectrospray source was operated
      at flow rates from 20 to 100 nL/min using pressure-driven flow, and uninterrupted
      operation for several hours is demonstrated without any noticeable signal
      degradation. The ability to fabricate multiple devices using injection molding or
      hot-embossing techniques of polymers provides a lower cost alternative to silica
      based devices currently utilized with mass spectrometry.

PMID- 11305665
TI  - Desorption-ionization mass spectrometry using deposited nanostructured silicon
      films.
AB  - We present a method for desorption ionization on silicon based on novel
      column/void-network-deposited silicon thin films. A number of different peptides
      and proteins in the < or = 6000 Daltons range are analyzed by time-of-flight mass
      spectrometry in this demonstration of our approach. A variety of sample
      preparation conditions, including the use of chemical additives, surface
      treatments, and sample purification are used to show the potential of mass
      analysis using deposited column/void-network silicon films for high throughput
      proteomic screening.

PMID- 11305666
TI  - Microseparation chips for performing multienzymatic dehydrogenase/oxidase assays:
      simultaneous electrochemical measurement of ethanol and glucose.
AB  - This report describes a new "lab-on-a-chip" protocol integrating on-line
      precolumn biocatalytic reactions of multiple (oxidase and dehydrogenase) enzymes
      and substrates with effective capillary electrophoresis microseparations and
      amperometric detection. The operation of the new oxidase/dehydrogenase
      reaction/separation microchip is illustrated for the simultaneous measurement of
      glucose and ethanol in connection to the corresponding glucose oxidase and
      alcohol dehydrogenase reactions, respectively. The enzymatic reactions generate
      hydrogen peroxide and NADH species that are separated (on the basis of their
      different charges) and detected amperometrically at the end-column thick-film
      detector. A driving voltage of 2000 V results in peroxide and NADH migration
      times of 74 and 230 s, respectively. Operating the gold-coated carbon detector at
      +1.0 V allows simultaneous anodic detection of both reaction products. Factors
      influencing the reaction, separation, and detection processes are examined and
      optimized. The applicability of the new multienzyme assay to wine samples is
      illustrated.

PMID- 11305667
TI  - Comparison of empirical peak capacities for high-efficiency capillary
      chromatographic techniques.
AB  - Experimental peak capacities for capillary gas chromatography (GC), capillary
      liquid chromatography (CLC), and capillary electrochromatography (CEC) were
      compared. To obtain a meaningful comparison, the following constraints were
      applied. First, the same sample (mixture of alkylbenzenes) was used as a test
      mixture for all three techniques; second, the same packing material and column
      diameter were used in CLC and CEC; and third, isothermal conditions were used in
      GC, while isocratic conditions were used both in CLC and in CEC. Comparison of
      peak capacities for the same total column efficiency (approximately 36000 plates)
      showed that the peak capacity of GC is greater than those of the liquid-phase
      separation techniques. Comparison of CEC and CLC for constant retention factor
      was also carried out. For this condition, the results depend on the particle size
      used; for 3-microm porous particles, CEC had a peak capacity larger than CLC due
      to higher efficiency from the flow profile generated by electroosmotic flow.
      However, when 1.5-microm nonporous particles were used, the peak capacities were
      approximately the same for both techniques. The effect of linear velocity on peak
      capacity was also studied for all three techniques. Practical conditions aimed at
      increasing peak capacities of liquid-phase separation techniques are discussed.

PMID- 11305668
TI  - Nanoflow gradient generator coupled with mu-LC-ESI-MS/MS for protein
      identification.
AB  - The large-scale identification of proteins from proteomes of complex organisms,
      and the availability of various types of protein and DNA databases, increasingly
      require the additional information provided by tandem mass spectrometry. HPLC and
      microLC coupled to ESI-MS/MS presently dominate the field of protein
      identification by tandem mass spectrometry and database searching. The analysis
      of protein digests is typically performed using HPLC or LC columns with 50-100
      microm diameters, requiring the delivery of solvent gradients at low to mid
      nanoliter per minute flow rates. This has been typically achieved using expensive
      generic HPLC pumping systems for the delivery of microliter per minute gradients
      that were either flow-split or sampled. Here we present an alternative system for
      the delivery of nanoliter per minute gradients. The inexpensive nanoflow gradient
      generator (etagrad) described here can be modulated to reproducibly deliver
      selected gradients. The performance of the etagrad on-line with a microLC-ESI
      MS/MS system has been demonstrated for the identification of standard protein
      digests. Moreover, the performance of the etagrad-microLC-ESI-MS/MS system, with
      protein prefractionation by IPG isoelectric focusing, was also evaluated for
      rapid study of yeast and human proteomes.

PMID- 11305670
TI  - Prediction of electrophoretic mobilities. 4. Multiply charged aromatic
      carboxylates in capillary zone electrophoresis.
AB  - The electrophoretic mobilites of aromatic carboxylates and sulfonates at zero
      ionic strength were correlated with models incorporating both hydrodynamic and
      dielectric friction. The hydrodynamic friction was predicted using either the
      Huckel spherical ion model or the Perrin ellipsoidal model. Dielectric friction
      is the charge-induced drag caused by the reorientation of the solvent dipoles in
      response to the analyte charge. Based on the Hubbard-Onsager and Zwanzig
      expressions, the dielectric friction is related to z2/V. Expressions
      incorporating both the hydrodynamic and dielectric frictional terms successfully
      predicted infinite-dilution mobilities to within 4.4%. The influence of
      dielectric friction ranged from 3-8% of the overall drag for singly charged
      analytes to 39% of the total frictional drag for 1,2,4,5-benzenetetracarboxylate.

PMID- 11305673
TI  - The effect of temperature oscillations on DNA sequencing by capillary
      electrophoresis.
AB  - Although capillary electrophoresis is a powerful sequencing technology, the low
      heat capacity of a capillary can make difficult the precise control of its
      temperature, particularly when the capillary is heated to reduce compressions in
      the separation of DNA sequencing fragments. In this paper, we demonstrate that
      minute oscillations in the capillary's temperature result in significant
      degradation in the number of theoretical plates, the resolution between adjacent
      peaks, and the number of bases of DNA sequence determined from the
      electrophoresis data. Temperature must be held stable to within 0.1 degrees C to
      obtain long read lengths. A Monte Carlo simulation demonstrates that this
      degradation is consistent with laminar flow induced by the periodic thermal
      expansion and contraction of the separation medium.

PMID- 11305675
TI  - Headspace analysis of engine oil by gas chromatography/mass spectrometry.
AB  - This study establishes the rationale necessary for determining the time to change
      engine oil. This is based on identifying gaseous components in new and used
      automobile lubricants. Key compounds, so-called "signature", are separated and
      identified qualitatively by coupled gas chromatography/mass spectrometry.
      Volatile antioxidants at zero miles and fuel contaminants at low mileage are
      observed in the headspace of engine oil. Several oxidative degradation components
      have been positively identified in the used oil, which include the following:
      acetaldehyde, acetone, butanal, 2-propanol, acetic acid, 2-hexanol, benzoic acid,
      benzaldehyde, and 1-pentanol. This study strongly suggests that the status of
      lubricating oil can be determined by the analysis of the gas phase above the oil.
      Most importantly, it opens the possibility of performing conditional maintenance
      of the combustion engine based on information obtained from gas sensors.

PMID- 11305676
TI  - Development of sandwich HPLC microcolumns for analyte adsorption on the
      millisecond time scale.
AB  - A new class of columns is reported that uses only microgram quantities of active
      support and that provides for the retention of biological compounds and other
      analytes on the millisecond time scale. This was accomplished by packing standard
      HPLC supports into layers as small as 60 microm in length and using only 90
      microg of support material. This provided columns with effective residence times
      in the millisecond time range when routine HPLC flow rates and pressures were
      used. The retention of analytes by such columns was examined under both
      adsorption- and diffusion-limited conditions. The RPLC adsorption of hemoglobin
      (a system with diffusion-limited retention) was found to give 95% binding in as
      little as 4 ms. The adsorption of fluorescein by an anti-fluorescein antibody
      column (an adsorption-limited system) gave 95% retention in 100-120 ms. One
      application examined for these columns was their use in a chromatographic-based
      competitive binding immunoassay. This used bovine serum albumin (BSA) as the
      model analyte, and fluorescein-labeled BSA was used for detection. The resulting
      approach had a contact time of 180 ms between the sample and an anti-BSA
      immunoaffinity microcolumn and provided a signal within 5-25 s after sample
      injection. The columns developed in this work should also be useful in other
      situations that involve a small amount of a stationary phase or that require
      short column residence times.

PMID- 11305677
TI  - Methylene retention indexes for isolated toxaphene congeners.
AB  - Toxaphene was a heavily used, broad-spectrum insecticide, which was banned in
      most countries in the 1980s. Early data suggested that a limited number of
      congeners in the technical mixture were responsible for its toxicity to insects.
      However, toxaphene research has historically focused on analyzing total
      toxaphene, largely due to insufficient analytical methodology to measure the
      individual congeners. In recent years, congener-specific toxaphene research has
      flourished due to analytical advances leading to the identification of several
      congeners, about 25 of which are commercially available. However, the high price
      of these standards may inhibit toxaphene research in some laboratories. We report
      here the methylene retention indexes for 28 isolated toxaphene congeners. When
      used in conjunction with mass spectrometry, methylene retention indexes provide
      an alternative method for identifying these compounds when direct comparison with
      standard compounds is not practical.

PMID- 11305681
TI  - Raman sensitivity enhancement for aqueous protein samples using a liquid-core
      optical-fiber cell.
AB  - We have demonstrated a sensitivity enhancement factor of 500 in aqueous solutions
      using a liquid core optical fiber (LCOF) Raman cell made from Teflon-AF. We were
      able to collect a spectrum of 54 microM lysozyme with a signal-to-noise ratio of
      31 in the LCOF Raman cell using 24 mW of laser power and 3 min of integration
      time. The lysozyme Raman intensity was only 1% of the background Raman intensity
      from water, but the water-subtracted lysozyme spectrum was still shot-noise
      limited and essentially free of nonrandom noise. The lack of nonrandom noise
      indicates that it should be possible to collect good quality Raman spectra of
      proteins such as lysozyme at even lower concentrations. The 2.4-microL sample
      volume of the LCOF Raman cell is an added benefit when limited quantities of
      sample are available. This volume of a 54 microM lysozyme solution corresponds to
      only 13 nanomoles or 1.9 microg of lysozyme.

PMID- 11305682
TI  - Neuroleptic malignant syndrome in children and adolescents.
AB  - Neuroleptic malignant syndrome is a rare but potentially fatal complication of
      treatment with antipsychotic medications. Prior to 1994, there was no accepted
      set of diagnostic criteria. This article presents four adolescents admitted at
      Cleveland Clinic Foundation from 1985 to 1998, illustrating the broad spectrum of
      neuroleptic malignant syndrome. A review of the pediatric literature is discussed
      as to the current risk factors, pathogenesis, management, and outcome. Early
      recognition and supportive and specific treatment of neuroleptic malignant
      syndrome reduced the morbidity and mortality.

PMID- 11305683
TI  - Pediatric patients with undetectable anticonvulsant blood levels: comparison with
      compliant patients.
AB  - Undetectable anticonvulsant blood levels indicate sustained noncompliance
      (several consecutive doses missed). We compared 91 consecutive outpatients with
      epilepsy and undetectable anticonvulsant blood levels to 100 patients seen during
      the same time period, verified as compliant by acceptable serum levels. We
      hypothesized that pay status, application for Supplemental Security Income,
      patient age, history of missed appointments, and functional status would differ
      between compliant and noncompliant patients. We were surprised to find large
      differences between clinic and insurance patients and between Caucasian and non
      Caucasian patients. The 100 compliant patients included 44 Caucasian and 56 non
      Caucasian patients, whereas only 9 of 91 noncompliant patients were Caucasian,
      and only 9 had insurance, compared to 32 compliant patients. Applications for
      Supplemental Security Income and history of missed appointments were
      significantly associated with noncompliance, but patient age, seizure type, and
      seizure control were not. Uninsured Caucasians were more often compliant than non
      Caucasians were. Many noncompliant patients had mild epilepsy, which was
      reportedly doing well. Race and pay status were closely correlated. Several
      noncompliant females became pregnant, whereas no compliant patients did.
      Compliant patients were much more likely to be accompanied by a parent or
      caretaker on clinic visits than noncompliant patients. Noncompliant patients had
      at least one acceptable subsequent serum level, although 2 patients with
      intractable epilepsy had undetectable serum levels on three or more occasions.
      Noncompliance may respond to discussion and advice. We reviewed 124 episodes of
      undetectable drug levels in the 91 noncompliant patients. Eighteen of these
      resulted in hospitalization, but in 25 cases, we were told that there had been no
      seizures since the preceding visit. Many noncompliant patients have infrequent
      seizures, even if they take little or no medication. Socioeconomic status
      influences health, life expectancy, and educational success, but it has been
      claimed to be irrelevant to compliance and adherence issues in epilepsy. Our data
      and the experience of other centers with childhood diabetes suggest that
      socioeconomic, racial, and family factors influence compliance or adherence to
      treatment for many chronic conditions. Educational efforts and support for
      parents at the start of anticonvulsant treatment may improve compliance.
      Uninsured patients missed more appointments and were much more likely to be
      noncompliant than insured patients. Attention to the special problems of Medicaid
      and minority children is needed.

PMID- 11305684
TI  - Effectiveness of N,N-dimethylglycine in autism and pervasive developmental
      disorder.
AB  - N,N-dimethylglycine, a dietary supplement, has been reported to be beneficial in
      children with autism and pervasive developmental disorder. We examined the
      effectiveness of dimethylglycine in children with autism and pervasive
      developmental disorder in a double-blind, placebo-controlled study. Thirty-seven
      children between 3 and 11 years of age with a diagnosis of autism and/or
      pervasive developmental disorder were gender and age matched and randomly
      assigned to receive either placebo or dimethylglycine for 4 weeks. All children
      were assessed before and after treatment on two behavioral measures, the Vineland
      Maladaptive Behavior Domain and the Aberrant Behavior Checklist. Standardized
      neurologic examinations before and after treatment on 33 children showed no
      change. An overall improvement on all behavioral measures was observed for both
      the placebo and the dimethylglycine groups. However, the improvement among the
      children who received dimethylglycine was not statistically different from the
      improvement observed among the children who received the placebo. The children
      who participated in this study were a heterogeneous group, and their apparent
      responses to the dimethylglycine varied. Some children appeared to respond
      positively to the dimethylglycine, and there was a smaller proportion of negative
      changes in the dimethylglycine group, but the quantitative changes in the
      dimethylglycine behavioral assessments were not significantly different from what
      was observed among children who received placebo.

PMID- 11305685
TI  - Febrile convulsions, ataxia, developmental delay, and obesity: a new syndrome?
AB  - We describe the association of recurrent complicated febrile convulsions,
      developmental delay, ataxia, and obesity in three unrelated girls. The three
      girls, aged 3 to 4 years, were all born to healthy, nonconsanguineous parents and
      have normal siblings. Their birth weight was appropriate for gestational age.
      They are not dysmorphic and have normal head circumference. Development is
      delayed; they all walked with an ataxic gait after the age of 2 years and started
      speaking at 3 years. Their growth charts are remarkably alike: they initially had
      a normal growth curve and around 24 months of age started to gain weight
      excessively. They all continue to suffer from complicated febrile seizures, which
      started before 12 months of age, and are resistant to prophylactic
      anticonvulsants. Metabolic evaluation is normal. They have normal magnetic
      resonance images and electroencephalograms. Fragile X and Prader-Willi syndromes
      were ruled out. We suggest that this is a new mental retardation syndrome that
      should be considered in children with recurrent febrile convulsions,
      developmental delay, and obesity. In a recent study, mutations in the beta4
      calcium channel were identified in the mutant epileptic mouse that presents with
      epilepsy, mental retardation, and ataxia. We hypothesize that a calcium channel
      gene may be involved in this syndrome.

PMID- 11305686
TI  - Williams (Williams Beuren) syndrome: a distinct neurobehavioral disorder.

PMID- 11305687
TI  - A didactic autobiography.

PMID- 11305688
TI  - Hot feet: erythromelalgia and related disorders.
AB  - Erythromelalgia is an extraordinary pain syndrome first described by S. Weir
      Mitchell in 1878. Episodes of severe burning pain in the distal limbs,
      accompanied by striking redness and warmth of the skin, are precipitated by heat
      or activity and can be terminated only by cooling the affected part. Primary
      erythromelalgia is a sporadic or autosomal-dominant hereditary disorder whose
      symptoms begin in childhood. Secondary erythromelalgia occurs in association with
      thrombocythemia, collagen-vascular diseases, diabetes mellitus, peripheral
      neuropathy, and use of certain drugs. Aspirin is effective for patients with
      thrombocythemia, but most other cases are very resistant to treatment. The
      pathogenesis of erythromelalgia has remained puzzling, especially the peculiar
      switch-like manner in which symptoms are turned on by heat and turned off by
      cold. Following Ochoa's description of the ABC (angry backfiring C nociceptors)
      syndrome, it seems plausible to regard erythromelalgia as a problem of sensitized
      skin polymodal C-fiber receptors. C-fiber threshold to activation by heat would
      be lowered to 32 degrees C to 36 degrees C; activated C fibers would cause
      vasodilation via axon reflexes with redness, heat, and swelling. Cooling would
      bring the nociceptors below threshold. Secondary erythromelalgia may result from
      humoral factors released from platelets or ischemic tissues or from C-fiber
      injury in some cases of neuropathy, whereas primary erythromelalgia could be due
      to a mutation of the capsaicin receptor.

PMID- 11305689
TI  - Progressive intracranial vascular disease with strokes and seizures in a boy with
      progeria.
AB  - Progeria, a rare genetic disorder, is characterized by severe growth failure,
      premature aging, and very early atherosclerosis with coronary artery and
      cerebrovascular disease. There has been no detailed description of progressive
      cerebrovascular changes in progeria or any attempted neurologic correlation of
      those changes. A 5-year-old boy developed signs of progeria at 4 months and
      hypertension at 4 years, treated with atenolol and dipyridamole. Left-sided
      seizures with a left hemiparesis occurred at 5 years. Magnetic resonance imaging
      (MRI) showed bilateral acute, subacute, and chronic cerebral infarctions.
      Magnetic resonance angiography disclosed severe stenosis of the left internal
      carotid artery. The child was also found to have an aortic valve vegetation and
      was anticoagulated. He subsequently developed right-sided seizures, and treatment
      with gabapentin was started. Later, severe stenosis also of the right internal
      carotid artery was found. MRI showed new left cerebral infarction. The child's
      neurologic symptoms almost certainly were caused by cerebral infarctions from
      progressive atherosclerosis of major intracranial vessels, but clinical
      neuroradiologic correlations were imprecise. There were multiple cerebral
      infarctions of different ages, some asymptomatic, others ipsilateral to the
      child's neurologic findings. No therapy has halted progression of the child's
      cerebrovascular disease.

PMID- 11305690
TI  - Neurodevelopmental delay associated with nonconvulsive status epilepticus in a
      toddler.
AB  - Nonconvulsive status epilepticus is a prolonged and continuous state of increased
      unawareness without overt motor seizures linked with repetitive generalized
      epileptic discharges. In children, it may occur de novo but more commonly may
      complicate a preexisting epileptic disorder. We report on a 2-year-old female who
      presented with global developmental delay as the main manifestation of
      nonconvulsive status epilepticus. Following valproic acid treatment, her motor,
      cognitive, and speech delays had gradually subsided and nearly completely
      resolved, in concert with normalization of electroencephalography (EEG). Hence,
      given a possible, albeit rare, presentation of nonconvulsive status epilepticus
      with global developmental delay, we suggest that EEG should be recommended in any
      infant who manifests neurodevelopmental delay.

PMID- 11305691
TI  - Hemihydranencephaly: case report and literature review.
AB  - Hydranencephaly is a severe brain condition characterized by complete or almost
      complete absence of cerebral cortex with preservation of meninges, basal ganglia,
      pons, medulla, cerebellum, and falx. It has been ascribed to different causes
      (infections, irradiations, fetal anoxia, medications, twin-twin transfusion), all
      leading to vascular disruption. Hemihydranencephaly is an extremely rare
      condition in which the vascular anomaly is unilateral. We report on a patient who
      was suspected to have hydrocephalus in utero; a brain magnetic resonance imaging
      scan showed left-sided hydranencephaly with preservation of basal ganglia. The
      patient developed signs of right hemiparesis but notably has only mild language
      delay. The available literature on hemihydranencephaly is reviewed.

PMID- 11305692
TI  - Infantile-onset paroxysmal dystonia: a diagnostic dilemma.
AB  - A 4-year-old boy presented with a history of paroxysmal dystonic posturing since
      birth. Episodes were triggered by stress, fatigue, and cold. Sleep, for as short
      as 1 minute, resulted in complete resolution of dystonia. He was developmentally
      normal, with no focal neurologic deficits. Cerebrospinal fluid, homovanillic acid
      (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were borderline low. On ictal
      spectroscopy, there was reduced blood flow to the right temporal region, caudate
      nuclei, and thalami. The typical infantile form of dystonia is benign, resolving
      by 2 years of age in an otherwise normal child. Our patient remains symptomatic
      at 4 years of age.

PMID- 11305693
TI  - Effects of gestational age and labor on the expression of prostanoid receptor
      genes in pregnant baboon cervix.
AB  - We sought to determine whether expression of genes encoding prostaglandin
      receptors varied with advancing gestational age and in association with the onset
      of spontaneous labor in the cervix of pregnant baboons. We performed cesarean
      hysterectomy on 14 pregnant baboons, five during spontaneous labor. Expression of
      genes was quantified by Northern analysis. Clear signals which were similar in
      estimated size to the human genes were detected by Northern analysis for the
      genes encoding the EP1, EP2, EP3, EP4, FP, IP and TP receptors. Expression of the
      gene encoding the prostanoid EP1 receptor increased with advancing gestational
      age prior to labor (r2 = 0.8, P = 0.007). There was a 4 fold lower level of
      expression of the EP2 receptor gene among animals in labor compared with animals
      not in labor (P = 0.006) and approximately 2-fold lower levels of expression of
      the FP and TP receptor genes (P < 0.0001 and P = 0.0002, respectively). We
      conclude that variation in the relative expression of prostanoid receptor types
      and sub-types may have a role in cervical dilatation in primate parturition.

PMID- 11305694
TI  - Identification of a prostaglandin E2 receptor splice variant and its expression
      in rat tissues.
AB  - The intercellular signalling actions of the lipid mediators, the eicosanoids, are
      transduced by a family of seven transmembrane domain receptors. Members of this
      receptor family with high affinity for PGE2 are termed EP receptors. There are
      four known EP receptor genes that are transcribed to generate EP1, EP2, EP3 and
      EP4 receptors. Two of these receptor transcripts, EP1 and EP3, are further
      modified by RNA splicing to give multiple receptor isoforms. The EP3 receptor is
      known to have multiple splice variants in human (9 variants), cow (4 variants),
      mouse (3 variants) and rat (3 variants). In the rat the three EP3 splice variants
      differ in the sequence of the intracellular C-terminus. We have identified a
      fourth splice variant of the rat prostaglandin EP3 receptor that has a greatly
      truncated intracellular C-terminus when compared to the other EP3 receptor
      isoforms. Using nested RT-PCR we have shown that this novel splice variant is
      strongly expressed in rat brain and is also found in spinal cord, kidney and
      spleen.

PMID- 11305695
TI  - Regulation of prostacyclin synthesis by angiotensin II and TNF-alpha in vascular
      smooth muscle.
AB  - We had previously established that in a model of Ang II-induced hypertension,
      administration of an anti-TNF-alpha antibody caused additional increases in mean
      arterial pressure. Production of vasodilator prostanoids (i.e. PGI2 and PGE2) is
      increased by Ang II in vascular smooth muscle and is part of a counter-regulatory
      mechanism that opposes increases in vascular tone. We, therefore, examined the
      effects of TNF-alpha on Ang II-induced increases in PGI2 production in vascular
      smooth muscle cells (VSMC). Addition of Ang II caused an increase in the
      production of PGI2, while addition of TNF-alpha had no effect. However,
      pretreatment with TNF-alpha potentiated the stimulatory effects of Ang II. The
      potentiating effect of TNF-alpha was neither at the level of prostacyclin
      synthetase nor at the level of acyl hydrolase activity. This potentiation was
      dependent on tyrosine kinase activity, as preincubation with genistein completely
      abolished the effect of TNF-alpha. TNF-alpha upregulated AA-induced PGI2
      synthesis, indicating that the effect of TNF-alpha is at the level of
      cyclooxygenase (COX). These data suggest that TNF-alpha potentiates Ang II
      induced synthesis of PGI2 and PGE2 in a tyrosine kinase-dependent manner, an
      effect that may contribute to the counter-regulatory influence of prostaglandins
      on the pressor effects of Ang II in the vasculature.

PMID- 11305697
TI  - The psychopharmacology of sex, part 2: effects of drugs and disease on the 3
      phases of human sexual response.

PMID- 11305696
TI  - Effects of indomethacin, luteinizing hormone (LH), prostaglandin E2 (PGE2),
      trilostane, mifepristone, ethamoxytriphetol (MER-25) on secretion of
      prostaglandin E (PGE), prostaglandin F2alpha (PGF2alpha) and progesterone by
      ovine corpora lutea of pregnancy or the estrous cycle.
AB  - Two experiments were conducted to determine the luteotropin of pregnancy in sheep
      and to examine autocrine and paracrine roles of progesterone and estradiol-17
      beta on progesterone secretion by the ovine corpus luteum (CL). Secretion of
      progesterone per unit mass by day-8 or day-11 CL of the estrous cycle was similar
      to day-90 CL of pregnancy (P > or = 0.05). In experiment 1, secretion of
      progesterone in vitro by slices of CL from ewes on day-8 of the estrous cycle was
      increased (P < or = 0.05) by LH or PGE2. Secretion of progesterone in vitro by CL
      slices from day-90 pregnant ewes was not affected by LH (P > or = 0.05) while
      PGE2 increased (P < or = 0.05) secretion of progesterone. Day 8 ovine CL of the
      estrous cycle did not secrete (P > or = 0.05) detectable quantities of PGF2alpha
      or PGE while day-90 ovine CL of pregnancy secreted PGE (P < or = 0.05) but not
      PGF2alpha. Secretion of progesterone and PGE in vitro by day-90 CL of pregnancy
      was decreased (P < or = 0.05) by indomethacin. The addition of PGE2, but not LH,
      in combination with indomethacin overcame the decreases in progesterone by
      indomethacin (P < or = 0.05). In experiment 2, secretion of progesterone in vitro
      by day-11 CL of the estrous cycle was increased at 4-h (P < or = 0.05) in the
      absence of treatments. Both day-11 CL of the estrous cycle and day-90 CL of
      pregnancy secreted detectable quantities of PGE and PGF2alpha (P < or = 0.05). In
      experiment 1, PGF2alpha secretion by day-8 CL of the estrous cycle and day-90
      ovine CL of pregnancy was undetectable, but was detectable in experiment 2 by day
      90 CL. Day 90 ovine CL of pregnancy also secreted more PGE than day-11 CL of the
      estrous cycle (P < or = 0.05), whereas day-8 CL of the estrous cycle did not
      secrete detectable quantities of PGE (P > or = 0.05). Trilostane, mifepristone,
      or MER-25 did not affect secretion of progesterone, PGE, or PGF2alpha by day- 11
      CL of the estrous cycle or day-90 CL of pregnancy (P > or = 0.05). It is
      concluded that PGE2, not LH, is the luteotropin at day-90 of pregnancy in sheep
      and that progesterone does not modify the response to luteotropins. Thus, we
      found no evidence for an autocrine or paracrine role for progesterone or
      estradiol-17 36 on luteal secretion of progesterone, PGE or PGF2alpha.

PMID- 11305698
TI  - Pharmacologic treatment of anxiety disorders in 1989 versus 1996: results from
      the Harvard/Brown anxiety disorders research program.
AB  - OBJECTIVE: This article reports on the pharmacologic treatment of patients
      diagnosed with generalized anxiety disorder (GAD) enrolled in a naturalistic long
      term study of anxiety disorders, with enrollment in 1989 through 1991 and follow
      up in 1996. METHOD: 711 patients were enrolled in the study during 1989-1991. At
      intake, 167 patients met DSM-III-R criteria for GAD; at 1996 follow-up, 103
      patients met these criteria. The patients were divided into 3 groups by
      diagnosis: GAD alone (N = 18 at intake, N =11 at follow-up), GAD comorbid with
      another anxiety disorder (N = 84 at intake, N = 52 at follow-up), and GAD
      comorbid with Research Diagnostic Criteria-defined major depressive disorder,
      with or without another anxiety disorder (N = 65 at intake, N = 40 at follow-up).
      The groups were evaluated at intake and follow-up on whether they received
      medication and the types of medication they received. RESULTS: Nearly one third
      of patients in the 1989-1991 sample were not receiving any medication for
      treatment of their anxiety disorder; in 1996, 27% of patients still were
      receiving no medication. There was a decrease in benzodiazepine treatment and an
      increase in antidepressant treatment in 1996 for GAD patients who did not have
      comorbid depression or another anxiety disorder. CONCLUSION: The finding of one
      quarter to one third of patients with GAD receiving no medication is consistent
      with previous observations of undertreatment of depression. The findings on
      medication type suggest a shift in the type of medications being prescribed for
      treatment of GAD from exclusive benzodiazepine treatment to the combination of
      benzodiazepine and antidepressant treatment.

PMID- 11305699
TI  - Risperidone liquid concentrate and oral lorazepam versus intramuscular
      haloperidol and intramuscular lorazepam for treatment of psychotic agitation.
AB  - BACKGROUND: Although agitation associated with psychosis is a common presentation
      in the psychiatric emergency service, there is no consensus concerning the best
      treatment. Standard treatment often consists of intramuscular (i.m.) injection of
      high-potency neuroleptics, sometimes combined with benzodiazepines. The objective
      of this study was to determine the relative efficacy, safety, and tolerability of
      oral risperidone versus intramuscular haloperidol, both in combination with
      lorazepam, for the emergency treatment of psychotic agitation in patients who are
      able to accept oral medications. METHOD: A convenience sample of psychotic
      patients admitted to a large psychiatric emergency service who required emergency
      medication for the control of agitation and/or violence was offered risperidone
      (2 mg liquid concentrate) and oral lorazepam (2 mg) as an alternative to standard
      care at the institution, haloperidol (5 mg i.m.) and lorazepam (2 mg i.m.).
      Subjects who refused the oral medications were given the intramuscular treatment
      as a component of routine care. RESULTS: Thirty patients were enrolled in each
      treatment group. Although men were significantly more likely to choose oral
      medication (chi2 = 5.165, p < .023), other demographic characteristics did not
      differ significantly between the 2 treatment groups. Both groups showed similar
      improvement in agitation as measured by 5 agitation subscales of the Positive and
      Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, and
      time to sedation. No patients receiving risperidone demonstrated any side effects
      or adverse events, while 1 patient receiving intramuscular treatment with
      haloperidol developed acute dystonia. One subject receiving risperidone required
      subsequent treatment with haloperidol for ongoing agitation. CONCLUSION: Oral
      treatment with risperidone and lorazepam appears to be a tolerable and comparable
      alternative to intramuscular haloperidol and lorazepam for short-term treatment
      of agitated psychosis in patients who accept oral medications.

PMID- 11305700
TI  - Which depressed patients respond to nefazodone and when?
AB  - BACKGROUND: Retrospective data analyses were conducted of a single-blind trial of
      993 outpatients with nonpsychotic major depression (DSM-III-R) treated for 12
      weeks with nefazodone to provide a more specific picture of the nature and timing
      of response or remission to acute-phase treatment. METHOD: All patients
      participated in a single-blind, 16-week lead-in to obtain responders eligible for
      a subsequent double-blind, randomized continuation phase trial. Outcomes were
      defined by the 17-item Hamilton Rating Scale for Depression (HAM-D). A > or = 50%
      reduction from baseline defined response, and a total HAM-D exit score of < or =8
      defined remission. RESULTS: Of all patients who entered the trial, 41.8% (last
      observation carried forward) responded at or before week 4 (early responders),
      and an additional 25.2% responded thereafter; 18.3% achieved remission at or
      before week 4; 33.6% achieved remission after week 4. Thus, 77.3% of those
      responding ultimately remitted. On average, remission followed response by 2
      weeks. The average end-of-treatment dose was 376 mg/day at exit (last observation
      carried forward). Responders or remitters (as opposed to nonresponders or
      nonremitters) had lower baseline depressive symptomatology and were more likely
      to be married or cohabiting. CONCLUSION: The full symptomatic benefit of
      antidepressant medication may not be apparent until completion of an 8- to 10
      week trial. A high number of responders ultimately attained remission. Baseline
      demographic and clinical features were not highly predictive of who would or
      would not benefit from nefazodone. For routine care, a minimal acute-phase trial,
      using a 50% reduction in baseline symptom severity to define response, should be
      8 weeks. Whether ultimate nonresponders can be identified earlier than 8 weeks
      deserves further study.

PMID- 11305701
TI  - An open trial of light therapy for women with seasonal affective disorder and
      comorbid bulimia nervosa.
AB  - OBJECTIVE: Many patients with seasonal affective disorder (SAD) have
      dysfunctional eating behaviors. Conversely, many women with bulimia nervosa have
      marked winter worsening of mood and bulimic symptoms. Controlled studies of light
      therapy in SAD and in bulimia nervosa have shown beneficial effects on mood and
      binge/purge symptoms. We explored the clinical use of light therapy in women with
      SAD who also had comorbid bulimia nervosa. METHOD: Twenty-two female patients
      diagnosed using DSM-IV criteria with both bulimia nervosa and major depressive
      disorder with a seasonal (winter) pattern were treated with an open design, 4
      week trial of light therapy (10,000 lux fluorescent light box with an ultraviolet
      filter, 30 to 60 minutes per day in the early morning). Patients were assessed
      before and after treatment with depression scales and with binge/purge diaries.
      RESULTS: Light therapy resulted in significant improvement in mood, with a mean
      56% reduction in 29-item Hamilton Rating Scale for Depression scores following
      treatment (p < .001). The frequency of binges and purges per week also
      significantly decreased (p < .001) from baseline by a mean of 46% and 36%,
      respectively. Two (9%) of 22 patients became abstinent of binge/ purge episodes,
      compared with 10 (45%) of 22 patients who met criteria for remission of
      depressive symptoms. The light therapy was well tolerated by patients.
      CONCLUSION: These results suggest that therapeutic effects of light therapy on
      mood and bulimic symptoms in patients with SAD and comorbid bulimia nervosa are
      sustained over at least 4 weeks. However, the low abstinence rate in bulimic
      symptoms indicates that light therapy may be most effectively used as an
      adjunctive treatment to medications and/or psychotherapy for bulimia nervosa.

PMID- 11305702
TI  - Triiodothyronine augmentation of selective serotonin reuptake inhibitors in
      posttraumatic stress disorder.
AB  - BACKGROUND: There is considerable comorbidity of major depression and
      posttraumatic stress disorder (PTSD), and antidepressants have been reported to
      be effective in treating PTSD. Addition of triiodothyronine (T3) to ongoing
      antidepressant treatment is considered an effective augmentation strategy in
      refractory depression. We report the effect of T3 augmentation of antidepressants
      in patients with PTSD. METHOD: T3 (25 microg/day) was added to treatment with a
      selective serotonin reuptake inhibitor (SSRI) (paroxetine or fluoxetine, 20
      mg/day for at least 4 weeks and 40 mg/day for a further 4 weeks) of 5 patients
      who fulfilled DSM-IV criteria for PTSD but not for major depressive disorder
      (although all patients had significant depressive symptoms). The Clinician
      Administered PTSD Scale, the 21-item Hamilton Rating Scale for Depression, and
      the Clinical Global Impressions-Severity of Illness scale were administered every
      2 weeks, and self-assessments were performed with a 100 mm visual analog mood
      scale. RESULTS: In 4 of the 5 patients, partial clinical improvement was observed
      with SSRI treatment at a daily dose of 20 mg with little further improvement when
      the dose was raised to 40 mg/day. This improvement was substantially enhanced by
      the addition of T3. Improvement was most striking on the Hamilton Rating Scale
      for Depression. CONCLUSION: T3 augmentation of SSRI treatment may be of
      therapeutic benefit in patients with PTSD, particularly those with depressive
      symptoms. Larger samples and controlled studies are needed in order to confirm
      this observation.

PMID- 11305703
TI  - Incidence and consistency of antiretroviral use among HIV-infected medicaid
      beneficiaries with schizophrenia.
AB  - OBJECTIVE: To investigate the incidence and consistency of antiretroviral (ARV)
      treatment in the period before the introduction of protease inhibitors among
      Medicaid beneficiaries in New Jersey who had both the human immunodeficiency
      virus (HIV) and schizophrenia. METHOD: HIV-infected Medicaid beneficiaries were
      identified using the HIV and acquired immunodeficiency syndrome (AIDS) registries
      for New Jersey; claims histories were used to identify patients diagnosed with
      ICD-9-CM schizophrenia and affective psychoses and to examine use of ARV drugs.
      RESULTS: Bivariate and multivariate analysis found no difference in the
      likelihood of receiving ARV drugs between patients with HIV and schizophrenia and
      HIV-infected patients without schizophrenia. However, once the therapy was
      initiated, patients with schizophrenia were more consistent users of ARV drugs.
      CONCLUSION: Results do not indicate that HIV-seropositive (HIV+) patients with
      schizophrenia are less adherent to HIV therapies than HIV+ patients without
      schizophrenia. In our study population, consistency of use was actually higher
      among HIV+ patients with schizophrenia, perhaps because their multiple diagnoses
      place them under closer medical scrutiny.

PMID- 11305704
TI  - A comparison of long-term outcome in first-episode schizophrenia following
      treatment with risperidone or a typical antipsychotic.
AB  - BACKGROUND: Most reports assessing the efficacy and tolerability of risperidone
      have involved patients previously treated with typical antipsychotics. Such
      patients are more likely to have a greater resistance or intolerance to
      treatment, thus restricting our interpretation of the impact a new treatment
      might have on the course of schizophrenia and possibly biasing the results. The
      present study examines the relative effectiveness of risperidone and typical
      antipsychotics in patients being treated for their first episode of
      schizophrenia. METHOD: From a cohort of 126 patients, 2 groups of 19 first
      episode DSM-III-R/DSM-IV schizophrenia patients matched for age, gender, length
      of illness, and length of treatment and treated with either a typical
      antipsychotic or risperidone for a minimum of 1 year were compared on a number of
      outcome dimensions during their course of treatment and at follow-up. Treatment
      allocation was not random, and patients were judged to be compliant with
      medication. Patients treated with typical antipsychotics were followed up for a
      statistically nonsignificantly longer time (mean = 2.7 vs. 1.9 years). RESULTS:
      Six patients (31.6%) from the typical antipsychotic group were admitted to the
      hospital within the first year following the index admission compared with 1
      patient (5.3%) in the risperidone group (admitted at month 14). Patients in the
      risperidone group showed a statistically significantly lower length of first
      hospitalization (p < .01), utilization of inpatient beds during the course of
      treatment (p < .001), and use of anticholinergic medication (p < .05). There were
      no statistically significant differences in symptom levels, either during the
      course of treatment or at follow-up; in the use of antidepressant, antianxiety,
      or mood-stabilizing drugs; or in changes in living circumstances or employment.
      CONCLUSION: These findings confirm at least equal long-term efficacy of typical
      antipsychotics and risperidone, but a possible advantage for risperidone in
      decreased service utilization and decreased use of anticholinergic drugs.

PMID- 11305705
TI  - Substitution of an SSRI with bupropion sustained release following SSRI-induced
      sexual dysfunction.
AB  - BACKGROUND: We examine changes in sexual functioning and depressive symptoms in
      patients' transition from a selective serotonin reuptake inhibitor (SSRI), which
      induced both a therapeutic response and sexual dysfunction, to bupropion
      sustained release (SR) over the course of an 8-week trial. METHOD: The study
      included 11 adults (8 women and 3 men) who had a DSM-IV diagnosis of major
      depressive disorder in remission (Hamilton Rating Scale for Depression [HAM-D]
      score < 11) and were receiving an SSRI. Depression (using the HAM-D) and sexual
      dysfunction (using the Changes in Sexual Functioning Questionnaire) were assessed
      at baseline, 2 weeks after bupropion SR was added to the current antidepressant
      (combined treatment), 2 weeks after taper of the SSRI was initiated and
      completed, and after 4 weeks of bupropion SR monotherapy. T tests were performed
      to assess changes in depression and sexual function. RESULTS: Patient
      participation dropped from the initial group of 11 at week 2 to 9 at week 4 and
      to 6 by week 8. Sexual functioning improved from week 0 (baseline) to week 2 and
      from week 2 to week 4. The patients showed no significant change in mean HAM-D
      scores in weekly comparisons during the study period; 55% of patients completed
      the substitution without significant adverse events or recurrence of depressive
      symptoms. CONCLUSION: Bupropion SR as a treatment for depression also alleviates
      sexual dysfunction due to SSRI treatment. Results show that sexual functioning
      improves after the addition of bupropion SR to SSRI treatment and continues to
      improve, after discontinuation of the SSRI, with bupropion SR treatment alone.

PMID- 11305706
TI  - Analysis of the QTc interval during olanzapine treatment of patients with
      schizophrenia and related psychosis.
AB  - BACKGROUND: There may be a temporal association between some antipsychotics and
      prolongation of the heart-rate-corrected QT interval (QTc) representing a delay
      in ventricular repolarization. QTc prolongation significantly exceeding normal
      intra-individual and interindividual variation may increase the risk of
      ventricular tachydysrhythmias, especially torsade de pointes, and therefore,
      sudden cardiac death. METHOD: Electrocardiogram recordings obtained as part of
      the safety assessment of olanzapine in 4 controlled, randomized clinical trials
      (N = 2,700) were analyzed. These analyses were conducted to characterize any
      change in QTc temporally associated with olanzapine, compared with placebo,
      haloperidol, and risperidone, in acutely psychotic patients (DSM-III-R and DSM
      IV) and to characterize variability and temporal course of the QTc in this
      patient population. Changes from baseline to minimum and maximum QTc were tested
      for significance, and baseline to acute-phase endpoint change in mean QTc was
      tested for significance within treatments and for differences between olanzapine
      and comparators. The possibility of a linear relationship between dose of
      olanzapine and mean change in QTc, as well as incidence of treatment-emergent
      prolongation of QTc (change from < 430 msec at baseline to > or =430 msec at
      endpoint), was tested. RESULTS: The incidence of maximum QTc > or = 450 msec
      during treatment was approximately equal to the incidence of QTc > or =450 msec
      at baseline. CONCLUSION: Results of these analyses suggest that olanzapine, as
      therapeutically administered to patients with schizophrenia and related
      psychoses, does not contribute to QTc prolongation resulting in potentially fatal
      ventricular arrhythmias.

PMID- 11305707
TI  - A preliminary double-blind, placebo-controlled trial of divalproex sodium in
      borderline personality disorder.
AB  - BACKGROUND: Borderline personality disorder is characterized by affective
      instability, impulsivity, and aggression and is associated with considerable
      morbidity and mortality. Since anticonvulsant agents may be helpful in such
      symptomatology, we compared divalproex sodium with placebo in patients with
      borderline personality disorder. METHOD: A 10-week, parallel, double-blind design
      was conducted. Sixteen outpatients meeting Structured Clinical Interview for DSM
      IV Axis II Personality Disorders criteria for borderline personality disorder
      were randomly assigned to receive placebo (N = 4) or divalproex sodium (N = 12).
      Change was assessed in global symptom severity (Clinical Global Impressions
      Improvement Scale [CGI-I]) and functioning (Global Assessment Scale [GAS]) as
      well as in specific core symptoms (depression, aggression, irritability, and
      suicidality). RESULTS: There was significant improvement from baseline in both
      global measures (CGI-I and GAS) following divalproex sodium treatment. A high
      dropout rate precluded finding significant differences between the treatment
      groups in the intent-to-treat analyses, although all results were in the
      predicted direction. CONCLUSION: Treatment with divalproex sodium may be more
      effective than placebo for global symptomatology, level of functioning,
      aggression, and depression. Controlled trials with larger sample sizes are
      warranted to confirm these preliminary results.

PMID- 11305708
TI  - Fatal body dysmorphic disorder by proxy.

PMID- 11305709
TI  - Treatment of refractory major depression with tramadol monotherapy.

PMID- 11305710
TI  - Emergence of PTSD in trauma survivors with dementia.

PMID- 11305711
TI  - Physical restraints, thromboembolism, and death in 2 patients.

PMID- 11305712
TI  - Lithium intoxication after administration of AT1 blockers.

PMID- 11305713
TI  - The clinical features of bipolar depression: a comparison with matched major
      depressive disorder patients.
AB  - BACKGROUND: Despite a resurgence of interest in the treatment of bipolar
      depression, there have been few controlled studies of the clinical
      characteristics of this condition. Identification of any distinctive clinical
      "signatures" of bipolar depression would be helpful in determining treatment
      options in the clinical setting. METHOD: From a cohort of 270 inpatients and
      outpatients assessed in detail during a DSM-IV major depressive episode, 39
      bipolar I disorder patients were identified and closely matched with 39 major
      depressive disorder patients for gender, age, and the presence or absence of DSM
      IV melancholic subtype. Patients were compared on a broad range of parameters
      including the Hamilton Rating Scale for Depression (depression severity), 54
      depressive symptoms, the Newcastle Endogenous Depression Diagnostic Index, 3
      family history items, 2 physical health items, the CORE scale (psychomotor
      disturbance), and 5 history items. RESULTS: Although the bipolar patients were no
      more severely depressed than the major depressive disorder controls, they were
      more likely to demonstrate psychomotor-retarded melancholic and atypical
      depressive features and to have had previous episodes of psychotic depression.
      These findings were largely duplicated even when the population was confined to
      those with DSM-IV melancholia. CONCLUSION: The clinical admixture of psychomotor
      retarded melancholic signs and symptoms, "atypical" features, and (less
      frequently) psychosis may provide a "bipolar signature" in clinical scenarios
      when there is uncertainty concerning the polarity of a depressive presentation.

PMID- 11305714
TI  - American Society of Pediatric Hematology/Oncology Distinguished Career Award goes
      to Beatrice C. Lampkin, M.D.

PMID- 11305715
TI  - Beatrice C. Lampkin, M.D. awarded the American Pediatric Hematology/Oncology
      Distinguished Career Award.

PMID- 11305716
TI  - Parental disclosure of HIV status.

PMID- 11305717
TI  - Detection of minimal residual disease in bone marrow during or after therapy as a
      prognostic marker for high-risk neuroblastoma.

PMID- 11305718
TI  - Nondisclosure of human immunodeficiency virus and hepatitis C virus coinfection
      in a patient with hemophilia: medical and ethical considerations.
AB  - This article discusses a medical and ethical dilemma: whether to disclose a
      positive HIV (human immunodeficiency virus)/HCV (hepatitis C virus) coinfection
      to an adolescent boy without symptoms with hemophilia despite the objections of
      his parents. An actual case history is presented and the dilemma faced by the
      medical team is discussed. Numerous family conferences, all excluding the
      patient, held during the last 5 years discussed the medical team's obligation for
      full disclosure, the emerging autonomy of the patient, and the potential for
      medical disaster (e.g., HIV transmission) if full disclosure were not permitted.
      Despite this, the family did not agree to allow disclosure. The patient and
      parents assured us of his sexual inactivity. Legal opinion was sought from the
      university counsel. The dilemmas are multiple. Is there a convincing argument to
      insist on disclosure of these facts to this patient, particularly when there is
      ambiguity regarding the appropriateness of HIV and HCV treatment? Does the
      ethical argument that he is at potential risk for transmitting HIV/HCV outweigh
      the rights of the family? What are the rights of the rest of the family? What are
      the rights of the minor? Is it our ethical responsibility to disclose a probably
      fatal diagnosis?

PMID- 11305719
TI  - Outcome of noncatheter-related thrombosis in children: influence of underlying or
      coexisting factors.
AB  - PURPOSE: To determine the hereditary and nonhereditary risk factors contributing
      to the development of noncatheter-related thrombosis in children. PATIENTS AND
      METHODS: Ninety-five children with noncatheter-related thrombosis from a single
      center were analyzed for clinical manifestations and outcome during a period of
      3.5 years. Patients with thrombosis were evaluated for congenital and acquired
      risk factors, and patients were screened for factor V Leiden, prothrombin 20210A
      mutations, protein C, protein S, antithrombin III deficiencies, and
      antiphospholipid antibodies. RESULTS: Twelve patients (12.5%) died of thrombosis
      that was associated with a nonmalignant underlying disorder, and 19 patients
      (20%) had significant complications, including amputation of extremities,
      epilepsy, hemiplegia, portal hypertension, recurrence of deep vein thrombosis,
      and postphlebitic syndrome. Two common mutations (factor V Leiden and prothrombin
      20210A) were found in 32.5% of the patients with thrombosis. The most frequent
      underlying disorder was infection (68%). Ninety-three patients (98%) had one or
      more risk factors. CONCLUSIONS: The coexistence of an underlying disorder and the
      presence of predisposing factors such as infection and the factor V Leiden
      mutation may cause high rates of death and complications in children with
      noncatheter-related thrombosis. The results of this study indicate that the
      underlying disorder and the site of thrombosis determine the rates of death and
      complications in children with thrombosis.

PMID- 11305720
TI  - Red blood cell folate and serum vitamin B12 status in children with sickle cell
      disease.
AB  - PURPOSE: To determine red blood cell (RBC) folate and serum vitamin B12 levels in
      children with sickle cell disease, SS-type, and to evaluate the associations of
      these nutrient levels with growth and hematologic parameters. PATIENTS AND
      METHODS: Subjects enrolled in this prospective, cross-sectional study were
      recruited from one tertiary care setting. Complete blood counts, measurement of
      red blood cell (RBC) folate and serum vitamin B12, anthropometric measures
      (height, weight, skinfold measurements), pubertal status, and 24-hour dietary
      recalls were obtained from 70 patients ages 1 to 19 years. RESULTS: Low RBC
      folate levels were found in 15% of the children. Fifty-seven percent of the
      sample had inadequate dietary folate intake. Three percent of the children had
      low serum vitamin B12 levels. All children and adolescents sampled had adequate
      dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12
      levels (P < 0.01) decreased with increasing age. CONCLUSIONS: More than half of
      the subjects had inadequate intake of folate from food, and despite daily folate
      supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were
      rare, and dietary vitamin B12 intake was adequate. Additional research is needed
      to explore the effects of improved folate status, the need for folate
      supplementation, and the relationship of folate, vitamin B12, and homocysteine
      levels and the risk for vascular damage and stroke in children with sickle cell
      disease.

PMID- 11305721
TI  - Successful chemotherapeutic decompression of primary endodermal sinus tumor
      presenting with severe spinal cord compression.
AB  - Management of spinal cord compression from a primary paraspinal endodermal sinus
      tumor (EST) is described. A 17-month-old child presented for treatment with near
      complete paraplegia secondary to spinal cord compression from a primary
      paraspinal EST. The child was treated with cisplatin-based chemotherapy without
      laminectomy or radiation therapy. Rapid resolution of symptoms was observed. The
      child had an excellent tumor response and complete neurologic recovery with no
      sequelae. Chemotherapy alone is an alternative to laminectomy or radiation
      therapy in the management of epidural cord compression from EST, even when the
      cord compression is severe.

PMID- 11305722
TI  - Relationship of chromosome 21 and acute leukemia in children with Down syndrome.

PMID- 11305723
TI  - Toward a rational use of recombinant thrombopoietin in the neonatal intensive
      care unit.

PMID- 11305724
TI  - p53, caspase 8, and regulation of apoptosis after ionizing radiation.

PMID- 11305725
TI  - Low-molecular-weight heparin therapy in children.

PMID- 11305726
TI  - Comparison of surgery and ultrasound guided sclerotherapy for treatment of
      saphenous varicose veins: must the criteria for assessment be the same?

PMID- 11305727
TI  - The home treatment of deep vein thrombosis with low molecular weight heparin,
      forced mobilisation and compression.
AB  - BACKGROUND: The aim of this prospective study was to analyse a group of patients
      with DVT (deep vein thrombosis) treated at home with LMWH (low-molecular weight
      heparin), compression and intensive mobilisation and to evaluate its feasibility,
      efficacy and safety from possible risks of pulmonary embolism. METHODS: From
      March 1997 to September 1999, 96 consecutive patients with diagnosed DVT were
      enrolled in a prospective study and treated at home with enoxaparin (Clexane Rh
      ne-Poulenc) administered subcutaneously at doses depending on body weight (1
      mg/kg) b.i.d. for a minimum of seven days. Oral anticoagulants were started two
      days before discontinuing LMWH and given later for three months according to the
      haemocoagulation parameters. All patients wore elastic second degree compression
      stockings during the whole period of treatment and for 12 months there after.
      They were encouraged to walk 1-3 km daily. The sites of thrombosis were ilio
      femoral vein--38 patients (40%), femoral or popliteal vein--32 patients (33%),
      crural veins--26 patients (27%). According to our surgical criteria two years ago
      17 patients would have been operated on and trombectomy performed. The diagnosis
      was made by compression ultrasonography using a colour duplex scanner (Acuscan
      125), by contrast phlebography, and platelet scintigraphy (Tromboscint test).
      Perfusion-ventilation scintigraphy of the lungs was performed only if there were
      clinical signs or even a suspicion of pulmonary embolism and on all patients with
      iliofemoral thrombosis. Perfusion gamagraphy of lungs was carried out on 51
      patients where thrombosis was localised in proximal veins. RESULTS: In 27
      patients there were signs of non-fatal pulmonary embolism (53%), but only seven
      patients (26%) suffered mild non-specific clinical signs; 20 patients with
      diagnosed pulmonary embolism (74%) were symptom-free. Out of 96 patients, three
      admitted to hospital (3%), 67 (70%) injected LMVH themselves and felt
      comfortable. Eight to 12 weeks after this treatment control sonography and
      phlebography were carried out in 70 patients to assess the localisation and
      progress of the thrombosis. In 51% (36 patients) partial and 31% (22 patients)
      total recanalisation was found. Five out of 96 complained of minor bleeding (5%).
      No thrombocytopenia was noticed. The first five days on home treatment were
      crucial. All patients were able to walk and live at home without difficulty. None
      of our patients with proximal deep vein thrombosis used a vena cava filter.
      CONCLUSIONS: Home treatment of DVT is possible and is effective, safe and less
      costly on average and per patient 40% in costs was saved compared with those of a
      hospital stay in spite of the greater expense of LMWH. The patients who received
      LMWH spent a mean of 1.2 days in the hospital, as compared with 12.7 days for the
      standard-heparin group.

PMID- 11305728
TI  - The value of computer analysis in predicting the long-term outcome of deep vein
      thrombosis.
AB  - BACKGROUND: The use of standardised computerised ultrasound images is an
      objective and quantitative method of determining the echogenicity of thrombus.
      This method had been applied to study the natural history of 100 acute thrombi
      over a period of one year to determine if early changes in echogenicity could
      indicate whether the thrombus would lyse, partially recanalise or remain
      occlusive. METHODS: A consecutive series of 100 above knee deep vein thromboses
      (DVT's) were analysed over a period of one year. The presence of a DVT was
      initially diagnosed by duplex scanning and the patients underwent follow-up scans
      at one week, one month, six months and at one year. A grey scale image of the
      thrombus was transferred to a computer at each examination and its grey scale
      median (GSM) was measured. The mean GSM's were calculated for each examination
      and compared. At one year the patients were divided into groups according to
      their final outcome (i.e. lysis, recanalisation or occlusion) and the mean GSM
      values from each group were compared. RESULTS: There were 100 proximal DVT's from
      89 patients. At one year 14% of the patients had died and 23% were lost to follow
      up. The mean GSM values increased over the one year period from 25.87+/-18.33 to
      a final value of 64+/-25.52 at one year. A total of 21 thrombi had fully resolved
      but there was no significant difference in their GSM values before resolution
      when compared to the other patients. Twenty-four patients had partially
      recanalised thrombi and 18 remained totally occluded. There was no significant
      difference in mean GSM values between these two groups until after six months
      when the permanently occluded venous segments had higher GSM values than those
      which partially recanalised. CONCLUSIONS: Measurement of GSM is an objective
      method of determining the degree of organisation of a thrombus and describes the
      subjective changes of individual thrombi. However, the organisation of a thrombus
      is a dynamic process and mean GSM values did not reflect these changes. Early
      changes in GSM could not predict the final outcome of the thrombus i.e. lysis,
      recanalisation or occlusion.

PMID- 11305729
TI  - The prevalence of factor V Leiden as a risk factor for venous thromboembolism in
      the population of North-Western Greece.
AB  - BACKGROUND: Many predisposing factors have been associated with the development
      of venous thromboembolism. Recently, Factor V Leiden has been described as a
      common genetic risk factor. The geographic distribution of this genetic
      abnormality in the general population greatly varies. The prevalence of the
      Factor V Leiden mutation in Europe is high, particularly in Greece, where
      according to some authors it is especially high. The purpose of this study was to
      estimate the prevalence of the Factor V Leiden mutation in patients presenting
      with at least one episode of venous thromboembolism and to compare it with that
      of the general population. METHODS: Blood samples were drawn from 388 subjects.
      240 healthy blood donors (controls) and 148 unselected patients with a history of
      one or more episodes of venous thrombosis. DNA analysis was performed using the
      polymerase chain reaction to amplify the factor V gene exon 10, and to detect the
      Factor V Leiden point mutation. RESULTS: DNA analysis revealed Factor V Leiden
      mutations in eight (3.3%) control subjects (seven heterozygous and one
      homozygous) and in twenty-four (16.2%) patients, (twenty-two heterozygous and two
      homozygous). The difference between the two groups is statistically significant
      (p<0.0001; chi2 test). CONCLUSIONS: The prevalence of the Factor V Leiden
      mutation in the general population of North-Western Greece is 3.3%, which is
      within the same range as that reported for other European countries. The Factor V
      Leiden mutation is one of the most important predisposing genetic factors in the
      development of venous thrombosis and was present in 16.2% of our patients.

PMID- 11305730
TI  - Colour Doppler ultrasonography of the ophthalmic artery: flow parameters in
      normal subjects. The significance of the resistance index.
AB  - BACKGROUND: The aim of this study was to assess the flow characteristics in
      ophthalmic arteries and to detect their possible relationships to those in the
      common and internal carotid arteries. METHODS: Sixty healthy subjects (age range
      20-74 years) with normal vascular findings, stratified by age and sex were
      recruited to the study. A colour Doppler ultrasound examination of the neck
      arteries was performed, followed by a colour Doppler ultrasound examination of
      the 120 ophthalmic arteries included. Peak systolic velocity, end diastolic
      velocity and resistance index (RI) of the common carotid, internal carotid and
      ophthalmic arteries, as well as the insonation depth of the ophthalmic arteries
      were measured. RESULTS: The mean values (standard deviation) of the measured
      parameters for the ophthalmic arteries were: insonation depth: 38.38 mm (2.60
      mm), peak systolic velocity: 34.71 cm/sec (6.38 cm/sec), end diastolic velocity:
      7.95 cm/sec (1.70 cm/sec), resistive index: 0.77 (0.04). The resistance index of
      the ophthalmic arteries was, in all cases, greater than that of the ipsilateral
      common carotid artery which in turn, was greater than that of the internal
      carotid. The value of the index in the ophthalmic arteries, when the circulation
      is normal in the extra- and intracranial arteries is rarely lower than 0.70.
      CONCLUSIONS: When an inversion of the ratio between the resistance index of the
      ophthalmic artery and that of the common carotid or an index value lower than
      0.70 in the ophthalmic artery is observed, further investigation is needed as
      this situation cannot be considered normal. The resistance index seems to be the
      most reliable parameter for the estimation of normal circulation in ophthalmic
      arteries.

PMID- 11305731
TI  - Colour Doppler diagnosis of perigraft flow following endovascular repair of
      abdominal aortic aneurysm.
AB  - BACKGROUND: Endovascular repair of abdominal aortic aneurysm is a relatively new
      surgical technique which is less invasive than conventional open abdominal
      surgery but is associated with a significant specific complication of endoleak.
      The aim of this study was to determine the accuracy of duplex ultrasound imaging,
      utilising colour Doppler, as the primary method for post surgical monitoring of
      endovascular aneurysm repair. METHODS:  EXPERIMENTAL DESIGN: a case cohort study
      of 45 patients undergoing endovascular repair of abdominal aortic aneurysm.
      SETTING: angiography, CT scanning and surgery performed at Westmead Hospital, a
      teaching hospital of the University of Sydney; patients followed postoperatively
      at the Westmead Vascular Laboratory, a dedicated vascular diagnostic ultrasound
      facility. PATIENTS: Forty males and five females, mean age 69.1 years (range 51
      to 84). INTERVENTIONS: patients underwent attempted insertion of an EVT
      (endovascular prosthesis) for exclusion of abdominal aortic aneurysm (mean
      diameter 5.3 cm; range 4.0 to 8.4 cm). Conversion to open repair was required in
      three cases (6.6%). An aorto-biliac graft was inserted in 28 patients, a tube
      graft in eight and an aorto-unilateral iliac graft with femorofemoral (or
      ilioilial) crossover graft in six. MEASURES: patients were followed over a period
      of 53 months (median follow-up time 15 months) with 106 colour Doppler scans of
      39 endovascular grafts (mean of 2.9 scans per patient). RESULTS: All aneurysms
      decreased in diameter (range 0.1 cm to 4.3 cm, mean 0.9 cm). Abnormal flow in the
      residual aneurysmal sac was found in three patients. In all three cases of
      endoleak the colour Doppler diagnosis was supported by CT scan and confirmed on
      angiography. The CT scans did not provide any additional information to that
      obtained by colour Doppler imaging. CONCLUSIONS: Colour Doppler provides an
      effective means of non-invasive follow-up assessment of patients who have had
      endovascular repair of abdominal aortic aneurysms.

PMID- 11305732
TI  - The independent correlation of the impact of lipoprotein(a) levels and
      apolipoprotein E polymorphism on carotid artery intima thickness.
AB  - BACKGROUND: Apolipoprotein E (apoE) plays a key role in lipoprotein metabolism.
      It occurs in three isoforms E2, E3 and E4. These isoforms have different impacts
      on plasma lipoprotein levels. The allele, or gene, coding apoE4 is considered a
      candidate for premature atherosclerosis development while the apoE2 gene is
      assumed to be protective. Lipoprotein(a) is also atherogenic and its increased
      plasma concentration is presumed to be an independent risk factor for premature
      atherosclerosis. Lipoprotein(a) is a protein depositing directly into the
      atheromatous plaques, enhancing cholesterol oxidation, competitively inhibiting
      plasminogen formation and thus having a prothrombogenic effect. The aim of our
      study was to establish a relationship between common carotid artery intima
      thickness and two independent risk factors, apoE polymorphism and elevation of
      plasma lipoprotein(a) levels. METHODS: A cross-sectional study was performed on
      114 patients who were referred to the lipid clinic for primary
      hyperlipoproteinaemia. The patients received no treatment prior to examination.
      Plasma levels of total cholesterol, triglycerides, HDL-cholesterol, LDL
      cholesterol, apoA, apoB, lipoprotein(a) and the apoE genotype were determined and
      the carotid artery intima thickness was measured using ultrasonography. RESULTS:
      The relative frequencies of apoE2, E3 and E4 were 0.049, 0.830 and 0.121. The
      equality of carotid intima thickness was tested using the Kruskal-Wallis test.
      Medians of intima thickness in a subgroup with the allele E2 were 0.72 mm, in a
      subgroup with the E3/E3 genotype 0.70 mm and in a subgroup with the E4 allele
      0.80 mm. The relationship between carotid intima thickness and lipoprotein(a)
      levels was tested using Spearman's correlation coefficient. CONCLUSIONS: No
      statistically significant differences of carotid intima thickness among subgroups
      divided according to their apoE genotype were found. No relationship between
      carotid intima thickness and lipoprotein(a) levels was found. On the contrary a
      close relationship between carotid intima thickness and age and also some of the
      plasma lipid variables was recorded using the method of multivariate linear
      regression.

PMID- 11305733
TI  - Angiotensin-converting enzyme gene insertion/deletion polymorphism and carotid
      artery wall thickness in patients with peripheral arterial occlusive disease.
AB  - BACKGROUND: It has been suggested that the deletion polymorphism of the
      angiotensin converting enzyme (ACE) gene is linked to a high risk of
      cardiovascular disease. The relationship between the insertion/deletion (I/D)
      polymorphism of the ACE gene and the carotid intima-media thickness in patients
      with peripheral arterial occlusive disease is unknown. We tested the hypothesis
      that the early progression of atherosclerosis in the extracranial carotid
      arteries in patients with peripheral arterial disease is associated with a
      genetic predisposition. METHODS: This prospective trial included 98 patients who
      only had manifestations of arteriosclerotic disease in peripheral arterial
      vascular regions of the lower extremities (stable stage II PAOD). Maximal common
      carotid intima-media thickness (mIMT) was measured using high resolution B-mode
      ultrasonography. Determinations of ACE gene polymorphism were made using a
      polymerase chain reaction technique. Multivariate regression analysis was
      performed to assess the influence of ACE genotypes, ACE activity and vascular
      risk factors on intima-media thickness. RESULTS: There was no significant
      association between intima-media thickness and ACE gene polymorphism. History of
      symptomatic peripheral arterial disease without local or systemic progression
      exists in subjects with the II-genotype significantly longer than in subjects
      with the DD genotype (p=0.01). With the presence of an II-genotype, there was
      also a tendency towards a thinner intima-media thickness. We found significant
      correlations between intima-media thickness and age (p<0.0001), fasting serum
      insulin (p=0.001), and lipoprotein (a) (p=0.008). CONCLUSIONS: In the present
      study involving patients with stage II peripheral arterial occlusive disease, ACE
      gene polymorphism could not be identified as a determining marker for the
      development of intima-media thickening in the common carotid artery. However, it
      can be assumed that there is a reduced risk for the systemic progression of
      atherosclerosis in patients with the II genotype.

PMID- 11305735
TI  - Seasonal variation in plasma levels of endothelin-1 and nitric oxide.
AB  - BACKGROUND: There is a seasonal variation in the incidence of stroke and coronary
      heart disease with admissions to hospital being higher in the colder months of
      the year. The mechanism whereby this winter prevalence of vascular disease occurs
      is still not fully understood. The aim of our study was to measure plasma levels
      of vasoactive compounds throughout the year to establish whether or not there
      were any fluctuations which could play a part in the higher winter incidence.
      METHODS: We measured plasma levels of the vasoconstrictive endothelin-1 (ET) and
      the vasorelaxant nitric oxide (NO) throughout the year. Blood samples were
      collected from 176 normal individuals. Samples were collected between 8.00 and
      10.00 hours after an overnight fast of at least 12 hours. RESULTS: Results were
      divided into two-monthly intervals and analysed using a Kruskal-Wallis one-way
      analysis of variance and Mann-Whitney U tests (SPSS). We found a significant
      seasonal variation in both parameters. Mean levels of endothelin were highest in
      January/February (4.0 pg/ml) and lowest in May/June (2.3 pg/ml), whereas plasma 5
      nitric oxide levels were lowest in January/February (5.7 microM) and highest in
      September/October (9.9 microM); p values were <0.0001 (Jan/Feb vs May/June) and
      0.049 (Jan/Feb vs Sept/Oct), respectively. CONCLUSIONS: The high levels of the
      vasoconstrictor endothelin combined with low levels of vasorelaxant nitric oxide
      may account in part for the increased incidence of stroke and coronary heart
      disease seen in these months.

PMID- 11305734
TI  - Changes in signal transduction in the platelets of patients with peripheral
      occlusive arterial disease.
AB  - BACKGROUND: The finding that platelets of patients with peripheral occlusive
      arterial disease (POAD) circulate in an activated state prompted us to study
      platelet signal transduction. We hypothesised that platelet hyperreactivity is
      caused by changes in intracellular signalling. METHODS:  EXPERIMENTAL DESIGN: a
      single blood sample was taken from the antecubital vein of each participant prior
      to the start of intravenous treatment with prostaglandins. SETTING: patients were
      recruited from our inpatient Department of Cardiology and Angiology at the
      University Hospital. PARTICIPANTS: 15 hospitalised patients with symptomatic POAD
      were randomly selected. Patients receiving antiplatelet drugs and those with
      diabetes were excluded. The control group consisted of 15 healthy volunteers from
      the medical staff. INTERVENTIONS: blood tests were performed on the day of
      admission before any therapeutic intervention. MEASURES: the platelet activation
      marker P-selectin was quantified on peripheral blood platelets before and after
      in vitro stimulation with platelet agonists (adenosine diphosphate, thrombin
      receptor activator peptide-6). The signal transduction cascade was also
      selectively blocked by preincubation with either: 1) forskolin, 2) phospholipase
      C inhibitor U-73122, or 3) bisindolylmaleimide. RESULTS: A stronger inhibitory
      effect on ADP-stimulated platelets was seen in patients with U-73122, as
      indicated by a decrease in mean fluorescence intensity of 51% versus 34% in
      controls (p<0.0005). CONCLUSIONS: Our findings support the assumption that
      changes in platelet signal transduction in POAD lead to platelet hyper
      reactivity.

PMID- 11305736
TI  - Weekly and seasonal variation of hospital admissions and outcome in patients with
      acute lower limb ischaemia treated by surgical and endovascular means.
AB  - BACKGROUND: The aim of this study was to investigate weekly and seasonal
      variation of hospital admissions, major amputations and mortality in patients
      treated for acute leg ischaemia by surgical and endovascular procedures. METHODS:
      EXPERIMENTAL DESIGN: Retrospective study. SETTING: University (5), central (16)
      and district (4) hospitals participating in the Finnish national vascular
      registry Finnvasc. PATIENTS: 1550 patients treated for acute leg ischaemia on the
      basis of the registry. INTERVENTIONS: Surgical or endovascular revascularisation.
      MEASURES: Day of the week of hospital admission, major amputation and death.
      RESULTS: The weekly pattern of the hospital admissions was significantly non
      uniform with a Monday peak and a weekend nadir. A tendency towards more hospital
      admissions in the winter season was found. PATIENTS hospitalised on Thursday or
      Friday tended to have a lower amputation rate compared to those hospitalised in
      any other day of week. The highest amputation and mortality rates were observed
      in the summer season. CONCLUSIONS: PATIENTS with acute leg ischaemia seek medical
      help in a non-uniform weekly and seasonal pattern with varying outcomes.

PMID- 11305737
TI  - Effect of intravenous iloprost and alprostadil (PGE1) on peripheral resistance
      during femoro-distal reconstructions.
AB  - BACKGROUND: A prospective, randomised study was undertaken to investigate the
      effect of intravenous infusion of either iloprost, the stable prostacyclin (PGI2)
      analogue, or alprostadil (prostaglandin E1) on peripheral resistance (PR) during
      femoro-distal reconstruction. METHODS: A prospective randomised study was
      performed with 35 patients. The PR Measurement of peripheral resistance involved
      a silicon tube temporarily inserted between the donor and recipient vessel. A
      flowmeter probe and a pressure transducer were inserted into the tube. The
      peripheral resistance was calculated as a quotient of pressure and flow under
      approximate physiological conditions. Patients received either alprostadil (4.4
      ng/min/kg) or iloprost (2 ng/min/kg) intravenously over ten minutes. After the
      end of the infusion, the measurements were taken for five minutes. RESULTS:
      Baseline peripheral resistance was similar for both groups (iloprost 0.76+/-0.54
      mmHg/ml/min, alprostadil 0.72+/-0.35 mmHg/ml/min, p>0.05). Following the
      measurement procedure, the final peripheral resistance in the iloprost group was
      reduced (0.57+/-0.33 mmHg/ml/min), but the difference to the alprostadil group
      (0.70+/-0.36 mmHg/ml/min) was not significant (p>0.05). The different decrease of
      ratio peripheral resistance (quotient between final and baseline resistance times
      one hundred) was highly significant (iloprost: 79.4+/-13.4% vs alprostadil:
      97.0+/-15.6%, p<0.01). CONCLUSIONS: Intravenous application of prostanoids,
      infused with usual doses over ten minutes during femoro-distal reconstructions,
      produces significant differences in decrease of peripheral resistance.
      Alprostadil only causes a slight drop of resistance, whereas iloprost causes a
      significant higher reduction of peripheral resistance.

PMID- 11305738
TI  - Superior vena cava thrombosis secondary to thoracic outlet syndrome. Case report.
AB  - A case of superior vena cava thrombosis secondary to the thoracic outlet syndrome
      is reported. The diagnosis was revealed by CT-scan and confirmed by phlebography
      performed to insert a catheter for intrathrombotic infusion of urokinase. The
      thrombolytic treatment was followed by complete clot lysis. A hyperabduction
      manoeuvre confirmed costoclavicular compression as the cause of the subclavian
      axillary vein thrombosis for which the patient underwent first rib resection.
      Axillary-subclavian vein thrombosis (or Paget-von Schroetter syndrome) is a
      relatively frequent complication of the thoracic outlet syndrome often treated
      with anticoagulants on the basis of a duplex examination. Involvement of the
      superior vena cava is not readily detected by duplex ultrasound so a partial
      thrombosis, with a possible fatal outcome could remain undiagnosed. Full
      investigation by phlebography or CT-scan is therefore recommended. In addition,
      transcatheter thrombolytic therapy has a lower incidence of follow-up
      complications than heparin.

PMID- 11305739
TI  - Extensive deep vein thrombosis in a young woman. Case report.
AB  - We report a case of a young lady with an extensive deep vein thrombosis (DVT)
      diagnosed by CT scan and duplex ultrasound examination. Contributory factors were
      relative immobilisation, oral contraception and hyperhomocysteinemia after
      methionine loading. No other thrombophilic factors could be found. The three main
      causes of hyperhomocysteinemia are genetic defects, nutritional deficiencies and
      insufficient elimination. In our case a genetic defect for one of the key enzymes
      of homocysteine metabolism, may be the underlying cause. Besides stopping oral
      contraceptive drugs, anticoagulation and supplementation with pyridoxine and
      folate was started. Family screening was carried out and revealed other members
      with hyperhomocysteinemia. Whether therapy with pyridoxine and folate can
      substantially reduce the recurrence of venous thromboembolic disease remains to
      be established.

PMID- 11305740
TI  - Hippocratic views with reference to the anatomical characteristics of "arteries"
      and "veins".
AB  - The anatomical knowledge, in the collection of books named after Hippocrates' the
      Hippocratic Corpus, is usually vague and limited. This is mainly due to the
      respect for the dead held by the ancients. Though the Hippocratic books, for the
      first time, supported the rationality of the aetiology of diseases, and prognosis
      and treatment were based on observation, the absence of dissection restricted the
      means of obtaining knowledge of the interior of the body until almost the time of
      the Renaissance. However in some cases, surprisingly enough, this ignorance is
      absent. In this essay we will attempt to elucidate some of the Hippocratic views-
      either erroneous or up to date--on the anatomy of the vascular system, mainly the
      "arteries" and "veins".

PMID- 11305741
TI  - The San Valentino's study.

PMID- 11305742
TI  - Evaluation of oxygen-dependent immunodefences of the polymorphonuclear cells of
      some tropical ruminants.
AB  - Activation of polymorphonuclear cells (PMNs) leads to the formation of
      superoxide, which is in turn dismutated to H2O2 by superoxide dismutase (SOD) and
      is partly responsible for oxygen-dependent microbicidal activity. However, no
      comparative information is available on the effect of SOD inhibition before PMN
      activation to allow simulation of the SOD defects that are known to occur in some
      ruminants. This paper attempts to examine the degranulative and phagocytic
      responses in buffalo, cattle and goat PMNs exposed to diethyldithiocarbamate, a
      known SOD inhibitor. The activity of glutathione peroxidase and reductase was
      increased in the presence of SOD inhibitor. On activation, H2O2 production
      increased significantly (p < 0.01), while SOD inhibition before the activation of
      PMNs caused a significant decline in the production of H2O2 (p < 0.05) in all the
      species studied. There was a significant increase (p < 0.05) in the phagocytosis
      of Candida albicans spores by buffalo PMNs activated with opsonized zymosan.
      Activation of bovine PMNs after exposure to the SOD inhibitor resulted in a
      significant decline (p < 0.05) in phagocytic activity; in the other species, the
      two values only approached significance. Among the activators, opsonized zymosan
      caused a significant increase in phagocytic activity as compared to
      lipopolysaccharide, particularly in the PMNs of buffaloes (p < 0.05). Increased
      fungicidal activity (p < 0.05) occurred with opsonized zymosan-activated PMNs of
      all the species studied. The fungicidal activity was found to decline in PMNs
      exposed to SOD inhibitor before activation (p < 0.05). Interestingly, the
      phagocytic activity of caprine PMNs was found to be lower than that of PMNs from
      cattle (p < 0.05).

PMID- 11305743
TI  - Nutritional condition affects the hepatic antioxidant systems in steers.
AB  - The objectives of this study were to evaluate the activity of antioxidant systems
      in the hepatic tissues of steers experimentally subjected to a restricted diet.
      Hence, the activities of superoxide dismutase (SOD) and reduced glutathione (GSH)
      and lipid peroxide levels were measured. Nine male Holstein steers were used.
      They were separated in two groups: three steers in group 1 (control) and six
      steers in group 2, which were subjected to a restricted diet that covered only
      60% of the maintenance requirements. After 30 days, the animals in both groups
      were killed and studies were completed. Both the CuZn-SOD and the glucose-6
      phosphate dehydrogenase activities were significantly decreased (p < 0.05) in
      group 2, reaching 68% and 60%, respectively, of the concentrations found in group
      1. The concentration of GSH in group 2 was 6.71+/-0.9 nmol/mg protein, which was
      significantly lower (p < 0.01) than that of the controls, 25.7+/-2.4 nmol/mg
      protein. In addition, the lipid peroxide levels were significantly increased (p <
      0.01) in group 2, being 50-60% higher than that in group 1. These results showed
      that the poor nutritional status caused modifications to the enzymatic
      antioxidant systems, with a lower ability to reduce oxidative compounds and a
      state of lipid peroxidation.

PMID- 11305744
TI  - Serum lipids and lipoproteins in clinically healthy male Camels (Camelus
      dromedarius).
AB  - Blood samples were collected from the jugular vein of 87 Iranian male dromedary
      camels of different age groups (<3, 3-5, 5-6 and 6-8 years). Variations in the
      serum concentrations of cholesterol, triglyceride, total lipid, very low-density
      lipoprotein (VLDL-cholesterol), low-density lipoprotein (LDL-cholesterol) and
      high-density lipoprotein (HDL-cholesterol) were investigated. The concentrations
      of cholesterol, triglyceride, total lipid, HDL-cholesterol, LDL-cholesterol and
      VLDL-cholesterol in the different age groups were significantly different (p <
      0.05). With an increase in the age of the animals, there were highly significant
      increases in the cholesterol, triglyceride, HDL-cholesterol and VLDL-cholesterol
      concentrations, whereas the concentration of LDL-cholesterol decreased (p <
      0.001).

PMID- 11305745
TI  - A preliminary comparative study of a dipstick colloidal dye immunoassay and two
      antigen-detection ELISAs for diagnosis of Trypanosoma evansi infection in cattle.
AB  - A dipstick colloidal dye immunoassay (DIA) was developed for the field diagnosis
      of Trypanosoma evansi infection using affinity-purified polyclonal antibodies
      (PcAbs) and the monoclonal antibody (McAb) 8B9. PcAbs were adsorbed onto Palanil
      Red dye particles and used as dye reagents. Dipsticks were dotted with four
      different antibodies; normal rabbit and mouse IgGs as negative controls, and anti
      T. evansi PcAb and McAb 8B9, which capture trypanosome antigens in the tested
      samples. Since the dye reagent bound to the captured antigens, the presence of
      coloured dots on the dipstick identified trypanosome infections. The sensitivity
      of the DIA was compared with two antigen detection ELISAs (Ag-ELISA); one was
      PcAb-based and the other was based on a combination of the same Mc- and PcAbs as
      were employed for the DIA. With a positive serum, the DIA detected trypanosomal
      antigen up to a dilution of 1:500 for both the PcAb and McAb dots, at which
      dilution the PcAb- and combination-based Ag-ELISA gave positive OD readings of
      0.13 and 0.36, respectively. When 124 field sera were tested, circulating
      antigens were detected in 51 (41%) samples by the DIA, and 76 (61%) and 49 (40%)
      samples by the PcAb- and combination-based Ag-ELISAs respectively, of which 48
      (63%) and 34 (69%) were also positive by the DIA.

PMID- 11305746
TI  - Review of canine transmissible venereal sarcoma.

PMID- 11305747
TI  - Lechiguana (focal proliferative fibrogranulomatous panniculitis) in cattle.
AB  - Lechiguana is a disease of cattle characterized by large, hard, subcutaneous
      swellings that grow rapidly and result in death after 3-11 months in untreated
      animals. Cattle treated with antibiotics recover. The disease has been reported
      from five states in south and southeastern Brazil. Histologically, the lesion
      consists of focal proliferation of fibrous tissue infiltrated by plasma cells,
      eosinophils, lymphocytes and sometimes neutrophils. The primary lesion is an
      eosinophilic lymphangitis, which results in eosinophilic abscesses, with
      occasional rosettes containing bacteria in their centres. Much experimental and
      epidemiological evidence, reviewed in this article, supports the suggestion that
      lechiguana is caused by an association of Pasteurella granulomatis (syn:
      Mannheimia granutomatis) and Dermatobia hominis.

PMID- 11305748
TI  - Toxicity testing of Senna occidentalis seed in rabbits.
AB  - The effect was investigated of administering ground Senna occidentalis seeds to
      rabbits in different concentrations (1%, 2%, 3% and 4%) in the ration. The
      experiment lasted 30 days and the toxic effects of the plant were evaluated on
      the basis of weight gain, histopathological, biochemical and morphometric
      parameters, as well as histochemistry and electron microscopy. Animals that
      received the ration containing 4% ground S. occidentalis seeds gained less weight
      (p < 0.05) and died in the third week. Histopathology revealed that the heart and
      liver were the main organs affected, with myocardial necrosis and centrolobular
      degeneration. There was a reduction in cytochrome oxidase activity in the
      glycogenolytic fibres, together with muscle atrophy, confirmed by the
      morphometric studies. Electron microscopy of the liver cells revealed dilated
      mitochondria, with destruction of the internal cristae.

PMID- 11305750
TI  - T2 relaxometry of brain in myotonic dystrophy.
AB  - We investigated the nature and extent of brain involvement in myotonic dystrophy
      (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients
      with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was
      performed at 0.5 T, and T2 values were calculated from signal intensity in two
      echoes. Regions of interest included: frontal, parietal, temporal, occipital and
      callosal (rostral and splenial) normal-appearing white matter; frontal,
      occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus
      pallidus and thalamus. All white-matter and occipital and right frontal cortex
      regions showed a significantly longer T2 in the patients. Multiple regression
      analysis, including grey- and white-matter T2 as dependent variables, plus age at
      onset and at imaging, disease duration, muscular disability, brain atrophy and
      CTG trinucleotide repeats as independent variables, revealed that only white
      matter T2 elongation and disease duration correlated positively. White-matter
      involvement in DM is more extensive than previously reported by MRI and
      neuropathological studies and seems to be progressive in the course of disease.

PMID- 11305749
TI  - Magnetic resonance imaging and 1H-magnetic resonance spectroscopy in amyotrophic
      lateral sclerosis.
AB  - We aimed to increase confidence in the combined use of MRI and proton MR
      spectroscopy (1H-MRS) in diagnosis of amyotrophic lateral sclerosis (ALS). We
      investigated 12 patients with ALS, seven definite and five probable, taking into
      account clinical measures of motor neuron function. On T2-weighted images we
      found high signal in the corticospinal tract in six and low signal in the primary
      motor cortex in seven of the 12 patients. Atrophy of the precentral gyrus was
      apparent in all the patients apart from one with probable ALS. Absolute
      quantification of cerebral metabolites using 1H-MRS demonstrated a significantly
      lower mean concentration of N-acetylaspartate (NAA) in the precentral gyrus of
      patients with probable and definite ALS (8.5 +/- 0.62) than in control subjects
      (10.4 +/- 0.71; P < 0.001). NAA concentration in primary motor cortex correlated
      with Norris scale scores (r = 0.30; P < 0.0001) but not with the ALS Functional
      Rating Scale score or disease duration. Significantly lower levels of NAA were
      detected in patients with low signal in the motor cortex than in those without (P
      < 0.01). Mean choline (Cho) and creatine (Cr) values did not differ between
      patients with ALS and controls.

PMID- 11305751
TI  - The circuit of Papez in mesial temporal sclerosis: MRI.
AB  - We looked at abnormalities in the circuit of Papez in patients with the mesial
      temporal sclerosis (MTS). We reviewed the MRI studies of 15 patients with
      probable MTS, seeking changes in the fornix, mamillary body, mamillothalamic
      tract, thalamus and cingulate and parahippocampal gyri. We correlated any
      abnormalities with each other and with clinical severity. Atrophy and/or signal
      change in one or more structures in the circuit of Papez were found in five
      patients. They involved the parahippocampal gyri in all five, the fornices in
      four, mamillary bodies in three, the thalamus in two and the cingulate gyrus in
      one. Changes in the fornix, mamillary body, thalamus or cingulate gyrus were
      always accompanied by hippocampal and parahippocampal atrophy. The patients with
      abnormalities of the circuit of Papez did not have more severe epilepsy than
      those without. Changes in the parahippocampal gyrus, including the entorhinal
      cortex and subiculum, in which forniceal fibres originate, may be crucial in
      causing abnormalities more distally in the circuit.

PMID- 11305752
TI  - Volume-selective proton MR spectroscopy for in-vitro quantification of
      anticonvulsants.
AB  - Administration of anticonvulsant drugs is clinically monitored by checking
      seizure frequency and by determining the serum concentration of the drug. In a
      few reports, drug concentrations in brain parenchyma have been determined using
      ex vivo techniques. Little is known about the in vivo concentration in the brain
      parenchyma. Our goals were to characterise the NMR spectra of the anticonvulsants
      at therapeutic concentrations, to determine the minimum detectable
      concentrations, and to quantify the drugs noninvasively. Volume-selective 1H-MR
      spectroscopy (MRS) was performed under standard clinical conditions using a
      single-voxel STEAM (stimulated-echo acquisition mode) sequence at 1.5 T. Spectra
      of the anticonvulsants carbamazepine, phenobarbital, phenytoin and valproate were
      acquired in vitro in hydrous solutions at increasing dilution. Phenytoin,
      phenobarbital and valproate were detectable below maximum therapeutic serum
      concentrations. Within therapeutic ranges, there was good agreement between
      concentrations determined by 1H-MRS and those by standard fluorescence
      polarisation immunoassay. Due to the absence of signals of brain metabolites, the
      aromatic protons of phenobarbital, phenytoin and carbamazepine, with resonance
      lines around 7.4 ppm, allow the drugs to be detected. Valproate, with two
      resonances around 1.2 ppm, should be differentiable from potential brain
      metabolites using nonlinear analysis of the brain spectrum. Volume-selective 1H
      MRS is therefore expected to be able to monitor anticonvulsant therapy in vivo.

PMID- 11305753
TI  - MRI demonstration of haemorrhage in the wall of a brain abscess: possible
      implications for diagnosis and management.
AB  - Haemorrhage in the wall of a brain abscess is rare and may falsely suggest a
      neoplasm on MRI. We describe two cases of haemorrhage in the wall of a brain
      abscess and discuss the role of in vivo proton MRS in the diagnosis and
      management.

PMID- 11305754
TI  - Practical injection-rate CT perfusion imaging: deconvolution-derived hemodynamics
      in a case of stroke.
AB  - Previously reported methods of dynamic, contrast-enhanced, CT perfusion imaging
      in acute stroke have been promising but substantially limited by their dependence
      on very rapid rates of injection (typically 10-20 ml/s in an arm vein). Newly
      available deconvolution software permits the use of lower rates of injection (e.
      g., 3-4 ml/s), and rapidly provides maps of cerebral blood flow, cerebral blood
      volume and mean transit time. We report the potential of CT perfusion imaging
      performed with an injection rate of 4 ml/s to provide information on the extent
      of hemodynamic abnormality, and to help distinguish viable from nonviable
      ischemic tissue. The slower injection rates permitted by deconvolution analysis
      substantially enhance the practicality of CT perfusion imaging for studying
      stroke.

PMID- 11305755
TI  - Intracerebral neurocysticercosis mimicking glioblastoma multiforme: a rare
      differential diagnosis in Central Europe.
AB  - A 47-year-old Greek man presented with a 4-week history of speech difficulties.
      CT and MRI revealed a low-density multilobulated cystic frontal mass with
      peripheral ring contrast enhancement adjacent to the sylvian fissure. Examination
      was normal. Blood tests revealed leucocytosis (16,000 cells/microl) and an
      elevated erythrocyte sedimentation rate (30/52). A malignant brain tumour was
      suspected and surgically removed. Histological examination disclosed
      intracerebral neurocysticercosis.

PMID- 11305756
TI  - High signal in the spinal cord on T2-weighted images in rapidly progressive
      tropical spastic paraparesis.
AB  - We report a 59-year-old woman with human T-cell lymphotrophic virus type-I (HTLV
      I) associated myelopathy/tropical spastic paraparesis who showed high signal in
      the cervical and thoracic spinal cord on T2-weighted and contrast enhancement on
      T1-weighted images.

PMID- 11305757
TI  - Extensive white-matter changes in case of adult polyglucosan body disease.
AB  - Extensive white matter signal changes were observed on T2-weighted images of a 49
      year-old man. He presented with a slowly progressive gait disorder, and finally
      developed severe dementia. Extensive metabolic and infectious investigations
      failed to disclose the underlying cause during life. Autopsy revealed adult
      polyglucosan body disease. We discuss MRI findings likely to permit this
      diagnosis if combined with clinical findings and nerve or skin biopsy.

PMID- 11305758
TI  - Agenesis of the internal carotid artery with a trans-sellar anastomosis: CT and
      MRI findings in late-onset congenital hypopituitarism.
AB  - A 29-year-old woman with a history of hypothyroidism since early childhood
      developed hypopituitarism. CT and MRI revealed anterior pituitary hypoplasia, an
      ectopic posterior lobe, a Chiari I malformation and agenesis of the right
      internal carotid artery with a trans-sellar anastomosis. This constellation of
      findings constitutes a previously unreported association in congenital
      hypopituitarism of late onset. The usefulness of imaging modalities and the
      pathogenic implications are also discussed.

PMID- 11305759
TI  - Subarachnoid hemorrhage associated with cyclosporine A neurotoxicity in a bone
      marrow transplant recipient.
AB  - We report subarachnoid hemorrhage associated with cyclosporine A (CSA)
      neurotoxicity after bone-marrow transplantation for chronic myelogenous leukemia.
      CT showed occipital subarachnoid hemorrhage. MRI confirmed this, and demonstrated
      cortical and subcortical edema in the posterior temporal, occipital, and
      posterior frontal lobes bilaterally, which was typical of CSA neurotoxicity.
      Recognition of CSA neurotoxicity as the cause of the subarachnoid hemorrhage
      obviated angiographic investigation. After cessation of cyclosporine therapy, the
      cortical and subcortical edema resolved on follow-up MRI with some residual blood
      products in the subarachnoid space.

PMID- 11305761
TI  - Traumatic basilar pseudoaneurysm with a basilar-cavernous arteriovenous fistula.
AB  - A traumatic pseudoaneurysm of the basilar artery with a basilar-cavernous sinus
      arteriovenous fistula was diagnosed in a 12-year-old girl using CT, MRI and
      angiography. It was successfully treated by coil embolisation. We speculate on
      the mode of formation of this rare traumatic lesion.

PMID- 11305760
TI  - Type III occipital condylar fracture presenting with hydrocephalus, vertebral
      artery injury and vasospasm: case report.
AB  - Occipital condylar fractures (OCF) are rare and have a high mortality rate. We
      report a patient with OCF who presented with acute hydrocephalus and died from
      diffuse vasospasm secondary to vertebral artery injury. A 45-year-old man fell 20
      feet from a deer stand and landed on his head. CT showed a type III OCF
      continuing to the anterior rim of the foramen magnum on the left, with a bone
      fragment pushing into the medulla, causing hydrocephalus. The patient was
      stabilized, and a four-vessel arteriogram showed diffuse vasospasm with complete
      occlusion of the left vertebral artery at the level of the OCF. To our knowledge,
      this is the first documented case of the conjunction of OCF, hydrocephalus, and
      vasospasm.

PMID- 11305762
TI  - Low-field interventional MRI in neurosurgery: finding the right dose of contrast
      medium.
AB  - MRI is increasingly being used as an interventional tool in neurosurgery. The
      field strength of "intraoperative" MR systems is usually lower than that of
      imagers commonly used for diagnostic purposes. However, lesion enhancement and
      apparent lesion extent depend on field strength. The aim of this study was to
      compare the contrast between intracranial, contrast-enhancing space-occupying
      lesions and the surrounding white matter obtained with low-field (0.2 T) and high
      field (1.5 T) MR imaging and to find the contrast medium dosage for low-field MRI
      that produces the same lesion-to-white-matter contrast as the one obtained with
      high-field MRI after the administration of a standard dose of the contrast
      medium. A total of 38 patients with intracranial metastases or high-grade glioma
      were enrolled in this study. T1-weighted spin-echo sequences were acquired. High
      field (1.5 T) studies were performed after the i.v. administration of 0.1 mmol
      gadolinium-DTPA/kg body weight. For low-field MRI (0.2 T) a dose escalation
      technique was used. T1-weighted sequences were repeated after each of three i. v.
      injections of 0.1 mmol gadolinium-DTPA/kg body weight. Thus, at the low-field
      examinations three T1-weighted sequences with a contrast medium dosage of 0.1,
      0.2 and 0.3 mmol gadolinium-DTPA/kg body weight were obtained. Lesion-to-white
      matter contrasts were calculated and compared. The average lesion-to-white-matter
      contrast obtained with high-field MR examinations was 1.63 (standard deviation
      0.32). In the low-field MR examinations the average lesion-to-white-matter
      contrast was 1.34 (0.2) after a single dose, 1.57 (0.2) after a double dose, and
      1.71 (.19) after a triple dose of contrast medium. The lesion-to-white-matter
      contrast of the high-field MR examination after a single dose of contrast medium
      was significantly higher than that of the low-field study after a single dose (P
      < 0.0001), but did not differ significantly from the low-field studies after a
      double (P = 0.28) or a triple dose (P = 0.17) of contrast medium. In a series of
      patients with contrast-enhancing space occupying brain lesions low-field MRI (0.2
      T) after a double dose of contrast medium yielded the same lesion-to-white-matter
      contrasts as high-field MRI (1.5 T) after a standard dose. This is an important
      finding to avoid errors in intraoperative MRI due to the immanently lower degree
      of lesion enhancement in low-field MR imaging.

PMID- 11305763
TI  - Communicating hydrocephalus secondary to a cardiac tumour compressing the
      superior vena cava.
AB  - An infant developing communicating hydrocephalus as a result of a rare cardiac
      tumour compressing the superior vena cava is reported. The development and
      regression of the hydrocephalus parallels the degree of obstruction to venous
      outflow. This finding is reviewed in the light of previous studies and case
      reports, and it is argued that the hydrocephalus is secondary to a reversible
      defect in cerebrospinal fluid absorption caused by the reversal of the normal
      cerebrospinal fluid to sagittal sinus pressure gradient.

PMID- 11305764
TI  - Radiation therapy in the management of childhood brain tumors.
AB  - Radiation therapy (RT) still plays a major role in the management of intracranial
      malignancies, together with surgical resection and, more recently, chemotherapy.
      This is a review of the experience with fractionated external beam RT. In
      medulloblastomas, combined modalities currently achieve a 5-year survival in
      excess of 70% in low-risk subgroups and 40% in the subgroups considered to be
      high risk. For the past decade, the emphasis has been on the quality of life in
      cured children. Recent advances have mainly aimed at limiting the toxicity of the
      "prophylactic" craniospinal irradiation by testing dose reductions and altered
      fractionations. Technical innovations have also greatly benefited gliomas: modern
      techniques dealing with 3D CT and MRI-based treatment combined with stereotactic
      positioning of the patients, achieve a high degree of conformity that might
      improve both local control and longterm neurocognitive and growth sequelae.

PMID- 11305765
TI  - Growth-inhibitory effect of adenovirus-mediated p53 gene transfer on
      medulloblastoma cell line, Daoy, harboring mutant p53.
AB  - To improve the survival rate, gene therapy, such as the replacement of
      inactivated tumor suppressor genes, has become a new investigational adjuvant
      treatment modality for human malignancies. We investigated the effect of
      adenovirus(Ad)-mediated transfer of wildtype p53 tumor suppressor gene on the
      medulloblastoma cell line, Daoy, which harbors mutant-type p53 gene. At 50
      multiplicity of infection (moi), immunohistochemical staining with p53 monoclonal
      antibody showed positive staining in all cells 2 days after Ad-CMV-p53 infection.
      The high expression of wild-type p53 protein was detected in Ad-CMV-p53-infected
      cells, and expression of wild-type p53 protein peaked on day 2 after the
      infection. The growth of Ad-CMV-p53-infected cells was greatly suppressed in
      vitro, and the Ad-CMV-p53 treatment significantly reduced the tumor mass in vivo.
      The mean weight of Ad-CMV- infected tumors was only 16% of those which were mock
      infected, and 25% of those which were Ad-CMV-beta-gal infected. On microscopic
      examination, Ad-CMV-p53-infected tumors showed numerous apoptotic bodies. This Ad
      CMV-p53 gene transfer showed high transduction efficacy and expression, resulting
      in significant growth inhibition of Daoy harboring mutant type p53.

PMID- 11305766
TI  - The clinical value of electroencephalogram/magnetic resonance imaging co
      registration and three-dimensional reconstruction in the surgical treatment of
      epileptogenic lesions.
AB  - With the rapid developments in image processing, new clinical applications of
      manipulation and three-dimensional (3-D) reconstruction of neuro-imaging are
      evolving. Combination with other non-invasive techniques aimed at localising
      electric sources in the brain is of particular interest. These techniques rely on
      the recording of brain electrical activity and/or the associated magnetic fields
      from multiple areas on the scalp. Data obtained from an electroencephalogram
      (EEG) or from magnetoencephalography (MEG) can be fused in 3-D arrangement with
      anatomical [magnetic resonance imaging/computerised tomography (MRI/CT)] and/or
      metabolic [positron emission tomography (PET)] data. Such techniques highlight
      information on the functional correlates of anatomical or space-occupying lesions
      and their role in the localisation of related symptomatic epilepsy. In the
      present study we report on methodological issues and preliminary clinical data on
      spectral EEG/MRI co-registration procedures, offering two examples of children
      presenting with hemispheric lesions, one frontal tumour and one temporal arterio
      venous malformation. The EEG was acquired from 32/64 electrode location. The
      electrode position and that of four reference points were measured with a dual
      sensor Polhemus 3D Isotrak digitiser. Sources of EEG activity were determined in
      3-D space with the inverse solution method low resolution electromagnetic
      tomography (LORETA), providing for each frequency component, the topographic
      distribution of active electrical sources. The positions of the reference points
      were also measured on MRI, and co-registration of EEG and MRI was achieved using
      a transformation algorithm. The reconstructed 3-D images of co-registered EEG/MRI
      clearly demonstrate the relationship between the space-occupying lesion and the
      epileptic activity. Preliminary results show that in all the patients it was
      possible to identify with a remarkable accuracy the 3-D topographic relationship
      between lesion and cortical areas showing localised abnormalities on the EEG. The
      present method could further enhance the understanding of the effect of resective
      treatment of structural lesions on brain functioning. The new combined images can
      be used in combination with image-guided surgery equipment to modify effective
      surgical resection.

PMID- 11305767
TI  - Magnetic resonance spectroscopy in neonatal hypoxic-ischaemic insults.
AB  - This article aims to review the major achievements of phosphorus (31P) and proton
      (1H) magnetic resonance spectroscopy (MRS) in the field of perinatal hypoxic
      ischaemic cerebral injury. Methodologies for applying MRS to the routine study of
      the infant brain are now well developed. Both 31P and 1H MRS reveal gross
      abnormalities in severe hypoxic-ischaemic injury--in 31P studies
      [phosphocreatine] and [adenosine triphosphate] are low whilst [inorganic
      phosphate] is high; 1H MRS reveals high [lactate] and reduced [N
      acetylaspartate]. The 31P abnormalities are not apparent in early spectra but
      develop after 12-24 h--a phenomenon termed "secondary energy failure". These
      metabolic changes have now been modelled, and investigations of cerebroprotective
      therapies are underway. Extensive long-term studies have revealed that both 31P
      and 1H MRS, performed within a few days of birth, have great prognostic utility.

PMID- 11305768
TI  - Pressure changes observed in Codman-Medos programmable valves following magnetic
      exposure and filliping.
AB  - OBJECTS: We wished to find what pressure changes were caused in Codman-Medos
      programmable valve by magnetic exposure and filliping. This pressure-adjustable
      valve system was used in an experimental investigation of the changes measured in
      the pressure setting following MR exposure and other impulses. METHODS: In one
      experiment, two valves were affixed to a human model: one was installed in the
      right retroauricular region and the other at the anterior chest wall. The
      pressure was changed in 58 (80.6%) of 72 tests in the valve in the right
      retroauricular region and in 46 (63.9%) of 72 tests in the valve at the anterior
      chest wall. In some tests with the valve pressure originally set at 200 mmH2O
      striking changes to lower pressures were observed. In the other experiment, the
      changes of pressure settings in seven patients with a shunt system installed were
      checked before and after random filliping with the tip of an index finger 50
      times. In all 7 patients, the pressures initially set were greatly changed, by up
      to 120 mmH2O of the maximum range. CONCLUSIONS: These results demonstrate that
      the pressure setting of the shunt system can be changed by various shocks,
      including magnetic impulses, and that the pressure level of the shunt system must
      be constantly monitored.

PMID- 11305769
TI  - A randomized trial of very early decompressive craniectomy in children with
      traumatic brain injury and sustained intracranial hypertension.
AB  - OBJECT: The object of our study was to determine, in children with traumatic
      brain injury and sustained intracranial hypertension, whether very early
      decompressive craniectomy improves control of intracranial hypertension and
      longterm function and quality of life. METHODS: All children were managed from
      admission onward according to a standardized protocol for head injury management.
      Children with raised intracranial pressure (ICP) were randomized to standardized
      management alone or standardized management plus cerebral decompression. A
      decompressive bitemporal craniectomy was performed at a median of 19.2 h (range
      7.3-29.3 h) from the time of injury. ICP was recorded hourly via an
      intraventricular catheter. Compared with the ICP before randomization, the mean
      ICP was 3.69 mmHg lower in the 48 h after randomization in the control group, and
      8.98 mmHg lower in the 48 hours after craniectomy in the decompression group
      (P=0.057). Outcome was assessed 6 months after injury using a modification of the
      Glasgow Outcome Score (GOS) and the Health State Utility Index (Mark 1). Two
      (14%) of the 14 children in the control group were normal or had a mild
      disability after 6 months, compared with 7 (54%) of the 13 children in the
      decompression group. Our conclusion was that when children with traumatic brain
      injury and sustained intracranial hypertension are treated with a combination of
      very early decompressive craniectomy and conventional medical management, it is
      more likely that ICP will be reduced, fewer episodes of intracranial hypertension
      will occur, and functional outcome and quality of life may be better than in
      children treated with medical management alone (P=0.046; owing to multiple
      significance testing P <0.0221 is required for statistical significance). This
      pilot study suggests that very early decompressive craniectomy may be indicated
      in the treatment of traumatic brain injury.

PMID- 11305770
TI  - The importance of valve alignment in determining the pressure/flow
      characteristics of differential pressure shunt valves with anti-gravity devices.
AB  - OBJECT: The proper functioning of shunt valves in vivo is dependent on many
      factors, including the valve itself, the anti-siphon device or ASD (if included),
      patency of inlet and outlet tubing, and location of the valve. One important, but
      sometimes overlooked, consideration in valve function is the valve location
      relative to the tip of the ventricular inlet catheter. As with any pressure
      measurement, the zero or reference position is an important concept. In the case
      of shunt valves, the position of the proximal inlet catheter tip is fixed and
      therefore serves as the reference point for all pressure measurements. This study
      was conducted to document the importance of this relationship for the
      pressure/flow characteristics of the shunt valve. METHODS: We bench-tested
      differential pressure valves (with integral anti-gravity devices; AGDs) from
      three manufacturers. Valves were connected to an "infinite" reservoir, and the
      starting head pressure for each was determined from product inserts. The inlet
      catheter tip was fixed at this position, and the valve body was moved in relation
      to the inlet catheter tip. Outflow rates were determined gravimetrically for
      positions varying between 4 cm above and 8 cm below the inlet catheter tip.
      CONCLUSIONS: All differential pressure valves utilized in this study that
      contained AGDs showed significant increases in outflow rate as the valve body was
      moved incrementally below the level of the inlet catheter tip. To allow
      functioning as a zero-hydrostatic pressure differential pressure valve, the AGD
      and the inlet catheter tip should be aligned at the same horizontal level.

PMID- 11305771
TI  - The treatment of meningiomas in the region of the cavernous sinus.
AB  - The diagnosis and treatment of meningiomas of the cavernous sinus remains a
      controversial part of skull base surgery practice. The most common presenting
      symptom headache is nonspecific. Visual loss and oculomotor disturbance are the
      next likely symptoms and signs. It is possible to achieve total tumor removal in
      about 50% of patients, but an increase in cranial nerve dysfunction occurs in
      nearly as many. Improvement of neurological function, except for vision, is
      unusual. Because of the risk of complicating cranial nerve dysfunction by
      surgery, focused radiation as an alternative treatment has been explored in a
      small number of patients. Unfortunately, volume reduction is only seen in about
      one-third, but risks do appear to be low and nearly 60% of patients recorded have
      improvement in preoperative cranial nerve deficits. With these indolent tumors,
      much longer follow-ups are required before the role of focused radiation can be
      assessed.

PMID- 11305772
TI  - Intracranial hemorrhage from an aneurysm encased in a pilocytic astrocytoma--case
      report and review of the literature.
AB  - The authors present an unusual complication of a recurrent chiasmal/hypothalamic
      pilocytic astrocytoma. From his second year of life onwards, the patient was
      repeatedly operated on and also underwent external radiation therapy (54 Gy total
      dose) 1 month after the first subtotal tumor resection. Nine years after
      irradiation, the patient was referred to our center with a sudden onset of severe
      headache, vomiting and neck stiffness. Computed tomography, magnetic resonance
      imaging, and cerebral angiography demonstrated an intratumoral, intraventricular,
      and subarachnoidal hemorrhage from an anterior communicating artery aneurysm
      encased in the pilocytic astrocytoma. The aneurysm was clipped and the patient
      recovered nicely from the hemorrhage. Three years later, the patient suddenly
      died of cardiac failure. Autopsy disclosed vessel wall changes compatible with
      radiation-induced vasculopathy. In light of this finding, the importance of
      radiation therapy and intracranial neoplasms for aneurysm formation is discussed.

PMID- 11305773
TI  - Spinal arachnoid cyst without neural tube defect.
AB  - Symptomatic arachnoid cysts of the spine are rare lesions in the pediatric age
      group. Although most commonly occurring in association with neural tube defects,
      such as myelomeningocele and diastematomyelia, in some cases the cysts appear in
      children without spinal anomalies. We describe a 12-month-old girl with lumbar
      intradural arachnoid cyst with progressive weakness of the lower limbs. There was
      full recovery after fenestration of the cyst.

PMID- 11305774
TI  - Spontaneous resolution of acute obstructive hydrocephalus in the neonate.
AB  - Spontaneous resolution of acute hydrocephalus without aspiration of cerebral
      fluid is rare. In a neonate born at full term this has only been reported once
      before. We report on one further case that was caused by intraventricular
      haemorrhage (IVH). The probable mechanism is resolution of the acute haemorrhage
      in the region of the aqueduct, resulting in resolution of the hydrocephalus
      itself. The importance of considering conservative management of acute
      hydrocephalus in the clinically stable neonate is emphasised.

PMID- 11305775
TI  - Intralaboratory validation of alternative endpoints in the murine local lymph
      node assay for the identification of contact allergic potential: primary ear skin
      irritation and ear-draining lymph node hyperplasia induced by topical chemicals.
AB  - We validated a two-tiered murine local lymph node assay (LLNA) with a panel of
      standard contact (photo)allergens and (photo)irritants with the aim of improving
      the discrimination between contact (photo) allergenic potential and true skin
      (photo)irritation potential. We determined ear weights to correlate chemical
      induced skin irritation with the ear-draining lymph node (LN) activation
      potential. During tier I LLNAs, a wide range of concentrations were applied on
      three consecutive days to the dorsum of both ears. Mice were exposed to UVA light
      immediately after topical application to determine the photoreactive potential of
      some test chemicals. Mice were killed 24 h after the last application to
      determine ear and LN weights and LN cell counts. It was possible to classify the
      tested chemicals into three groups according to their threshold concentrations
      for LN activation and skin irritation: (1) chemicals with a low LN activation
      potential and no or very low skin irritation potential; (2) chemicals with a
      marked LN activation potential higher than a distinct skin irritation potential;
      and (3) chemicals with LN activation potential equal to or lower than their skin
      irritation potential. Group 1 consisted only of contact allergens, indicating
      that LN activation in the absence of skin irritation points to a contact
      allergenic activity. Since groups 2 and 3 comprised irritants and contact
      allergens, a tier II LLNA protocol was used to finally differentiate between true
      irritants and contact allergens. Briefly, mice were pretreated with mildly to
      moderately irritating concentrations of the chemical to the shaved back and after
      12 days were challenged on the ears as described above in order to elicit a
      contact allergenic response in the ear skin and the ear-draining LN. With this
      approach, tier II LLNAs have to be conducted only in cases for which skin
      irritation potential is in the range of LN activation potential and no structure
      activity relationship data indicating a contact allergenic hazard are available.

PMID- 11305776
TI  - Bismuth overdosing-induced reversible nephropathy in rats.
AB  - Overdosing of colloidal bismuth subcitrate (CBS), used to treat peptic ulcers and
      Helicobacter pylori infections, has been reported to result in serious, though
      reversible, nephrotoxicity in humans. However, little is known about the nature
      of the renal damage induced by bismuth (Bi), and no well-described experimental
      model exists. Single large oral CBS doses (0.75, 1.5, and 3.0 mmol Bi/kg) were
      administered to three groups of 20 female Wistar rats. A control group (n = 20)
      received only the vehicle. Standard kidney function parameters, urinary excretion
      of N-acetyl-beta-D-glucosaminidase (NAG) and the Bi content were monitored in
      blood, urine, liver, and kidneys for 14 days. A dose of 3.0 mmol Bi/kg, 100 times
      the daily therapeutic dose, caused kidney damage within 6 h as detected by
      proteinuria, glucosuria, and elevated plasma urea and plasma creatinine levels.
      The kidneys of all animals, except two that died, recovered functionally within
      10 days. At a dose of 1.5 mmol Bi/kg, clinical parameters changed less and
      normalized within 48 h, whereas a dose of 0.75 mmol Bi/kg induced no changes.
      Histological evaluation revealed that the S3 tubular segment necrotized first
      with additional necrotization of the S1/S2 segment when more Bi was absorbed. The
      lesions were accompanied by interstitial infiltrates of CD45+ leukocytes. In
      summary, we developed a rat model for Bi-induced reversible nephropathy. A large
      single oral overdose of CBS administered to Wistar rats led to damage to the
      proximal tubule, especially in the last segment.

PMID- 11305777
TI  - Does the polymorphism of cytochrome P-450 2E1 affect the metabolism of N,N
      dimethylformamide? Comparison of the half-lives of urinary N-methylformamide.
AB  - The aim of this study was to clarify whether phenotypic variation exists when
      subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are exposed to
      N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirmed in 123
      healthy male volunteer subjects. Of the 123 subjects, the numbers of c1
      homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1,
      respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, and the
      one c2 homozygote (mean age: 22.7 years, range: 20-27 years) were exposed to DMF
      vapor twice, once via the skin and once via the lung, for a total of 8 h per
      subject at a concentration below 10 ppm, the occupational exposure limit
      recommended by the Japan Society for Occupational Health, the American Conference
      of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft,
      at 27 degrees C and 44% relative humidity. Exposure levels were 6.2+/-1.0 ppm in
      dermal exposure and 7.1+/-1.0 ppm in inhalation exposure. Urine samples were
      collected until 72 h after exposure. The half-lives of urinary N-methylformamide
      (NMF) were obtained as the phenotype. The average urinary NMF half-lives of the
      c1 homozygotes, the c2 heterozygotes, and the c2 homozygote were 3.86+/-1.90,
      4.38+/-1.53, and 4.2 h after dermal exposure, and 1.58+/-0.42, 1.84+/-0.61, and
      3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were
      not significantly different from those of the c2 heterozygotes, and there were no
      differences between the NMF half-lives on the subjects with and without the c2
      allele. Even though the data were obtained from only one c2 homozygote, it is
      noteworthy that the NMF half-life of this subject was slightly less than that of
      the c1 homozygotes after respiratory exposure.

PMID- 11305778
TI  - High-performance liquid chromatography/fluorescence detection of S
      methylglutathione formed by glutathione-S-transferase T1 in vitro.
AB  - Glutathione-S-transferase T1 (GSTT1-1) is a major isoenzyme for the
      biotransformation of halomethanes. The enzyme activity is located, among other
      places, in human liver and erythrocytes and is subject to a genetic polymorphism.
      Metabolism of the halomethanes via GSTT1-1 yields S-methylglutathione (MeSG). A
      new HPLC assay for the enzymatic formation of MeSG was developed. The glutathione
      conjugate was derivatized with 9-fluorenylmethyl chloroformate, followed by
      reverse-phase HPLC with gradient elution and fluorescence detection. The limit of
      detection was as low as about 39 pmol MeSG on-column. Including derivatization
      and HPLC analysis, samples could be run at 42-min intervals, thus enabling a high
      sample throughput. The entire method was validated for analyte recovery (78.2%)
      and for variations in detector response with replicated injections (11.8%) and
      with analyses on each of 11 consecutive days (15.2%) with erythrocyte lysate
      incubations as the matrix. The time-, protein-, and substrate-dependences of the
      enzymatic catalysis with the model substrates methyl bromide (MeBr) and methyl
      chloride (MeCl) were studied. Due to its strong electrophilic character, MeBr
      caused a high level of spontaneous MeSG formation from glutathione in a protein
      free medium and a substrate-trapping side reaction in the presence of proteins.
      Therefore, enzymatic MeSG formation rates may only be determined with MeBr
      concentrations of at least 3000 ppm in the presence of limited amounts of protein
      (e.g. 100 microl erythrocyte lysate). In contrast, MeCl showed a lower alkylating
      potential allowing enzymatic catalysis to be the dominant reaction in incubations
      with 10,000 ppm MeCl and 2 ml erythrocyte lysate.

PMID- 11305779
TI  - Effects of iodine on inducible nitric oxide synthase and cyclooxygenase-2
      expression in sulfur mustard-induced skin.
AB  - In a previous study we demonstrated the protective effect of topical iodine as
      postexposure treatment for sulfur mustard (SM) application. The iodine treatment
      results in significantly reduced inflammation and necrosis and increased
      epidermal hyperplasia. The expression and localization of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase 2 (COX-2) in paraffin-embedded skin samples
      from that study were evaluated in the present investigation. We compared the
      immunoreactivity of iNOS and COX-2 using five samples from each of the following
      four test sites: untreated control sites, SM-exposed sites, sites treated with
      iodine mixture 15 min after SM exposure, and sites treated with iodine 30 min
      after SM exposure. All animals were killed 2 days after irritant exposure. iNOS
      immunoreactivity was present only in skin sites exposed to SM without iodine
      treatment. The ulcerated skin was covered with a relatively thick band of exudate
      composed of iNOS-immunostained polymorphonuclear cells and macrophages. In
      untreated skin, COX-2 immunostaining was limited to the thin suprabasal epidermal
      layer. In SM-exposed skin, induction of COX-2 was noted in inflammatory cells
      located close to the site of epidermal injury. In skin sites treated with iodine
      15 or 30 min after SM exposure, the regenerating hyperplastic epithelium showed
      moderate cytoplasmic staining localized to the epithelium overlying the basal
      layer. This pattern of staining was also present in the nearby dermal
      fibroblasts. Thus, in contrast to the skin samples exposed to SM without iodine
      treatment, the epidermal layer expressing immunohistochemical positivity for COX
      2 was thicker and corresponded to the epidermal hyperplasia noted in samples
      treated with iodine. It is well documented that prostaglandins (PGs) promote
      epidermal proliferation, thereby contributing to the repair of injured skin. That
      the induction of the COX-2 shown in our study may also play a role in the healing
      process is indicated by the present evidence. The results suggest that nitric
      oxide radicals (NO*) are involved in mediating the damage induced by the SM and
      that iodine-related reduction in acute epidermal inflammation is associated with
      reduced iNOS expression.

PMID- 11305780
TI  - No parallel relationship between nitric oxide production and wet dog shakes
      susceptible to nitric oxide synthase inhibitors following systemic administration
      of paraquat in rats.
AB  - Shaking behavior, so-called wet dog shakes (WDS), in rats is characteristic
      behavior indicating morphine abstinence in morphine-dependence and central
      excitation in relation to seizures elicited by chemicals or electrical
      stimulation. We have found that paraquat (PQ), a nonselective herbicide,
      administered systemically to rats induces WDS in a dose-dependent manner. PQ
      induced WDS are suppressed by nitric oxide (NO) synthase (NOS) inhibitors, but
      this suppression is not reversed by an NO precursor, L-arginine (L-Arg). The
      present study was performed to determine whether the NO system is associated with
      PQ-induced WDS in rats. A time-course study on the frequency of WDS for each 30
      min period up to 120 min after PQ administration (70 mg/kg, s.c.) revealed that
      significant induction of WDS occurred during the first and second 30-min periods,
      that is within 60 min of PQ administration. A nonselective NOS inhibitor, Nomega
      nitro-L-arginine (L-NA; 30 mg/kg, i.p.), reduced the frequency of the PQ-induced
      WDS during both of these periods, but the reduced frequency was not reversed by L
      Arg (500 mg/kg, i.p.) in either period. Significant induction of WDS occurred
      when PQ (50 nmol) was administered directly into the ventral or dorsal
      hippocampus, but not when administered into the amygdala or the caudate putamen,
      indicating that the hippocampus plays an important role in PQ-induced WDS. The
      WDS after the administration of PQ into the dorsal hippocampus was significantly
      suppressed by pretreatment with L-NA (30 mg/kg, i.p.). The extracellular levels
      of nitrite (NO2-) and nitrate (NO3-), the oxidative products of NO, in the dorsal
      hippocampus determined by in vivo microdialysis, were stimulated after systemic
      PQ administration (70 mg/kg, s.c.) in urethane-anesthetized rats. The increases
      in extracellular NO2- and NO3- were inhibited by L-NA (30 mg/kg, i.p.), and this
      inhibition was partly reversed by L-Arg (500 mg/kg, i.p.). The increases in
      extracellular NO2- and NO3- in the dorsal hippocampus appeared 60 min after PQ
      administration, when the WDS had occurred and disappeared. These findings suggest
      that NO production in the hippocampus plays a minor role in PQ-induced WDS in
      rats and that the suppression of PQ-induced WDS by NOS inhibitors might be
      mediated though complex mechanisms in the brain.

PMID- 11305781
TI  - The effect of postnatal age on L-2-chloropropionic acid-induced cerebellar
      granule cell necrosis in the rat.
AB  - L-2-Chloropropionic acid (L-2-CPA) selectively damages the cerebellum in adult
      rats. The rat cerebellum continues to develop postnatally during the first 4
      weeks of life. In this study we examined the neurotoxic effect on rats of
      increasing postnatal age. Daily oral dosing of rats aged 56 days with 250 mg/kg
      per day of L-2-CPA for 3 days produced necrosis to neurons in the cerebellar
      granule cell layer and to neurons in the medial/ventral region of the habenular
      nucleus. Rats aged 22 days were resistant to the cerebellar toxicity while rats
      aged 32 days and older were sensitive. A single large oral dose of 500 or 750
      mg/kg L-2-CPA produced no clinical signs of neurotoxicity or lesions in the
      cerebellum 48 h after dosing in 22-day-old rats. Daily dosing of 22-day-old rats
      at 250 mg/kg per day L-2-CPA for 10 days also produced no signs of neurotoxicity
      or reduction in body weight gain, although histological examination of the brain
      revealed slight neuronal cell necrosis in the granule cell layer of the
      cerebellum with a minimal effect in the medial/ventral region of the habenular
      nucleus. In contrast, daily dosing of rats aged 32, 38, 48 and 58 days with 250
      mg/kg per day of L-2-CPA for 3 days produced clear signs of neurotoxicity which
      were associated with reduced body weight gain and loss of hindlimb function. In
      these rats there was clear evidence of neuronal cell loss in the cerebellar
      granule cell layer and medial/ventral region of the habenular nucleus. This study
      showed that the postnatal developing cerebellum is resistant to L-CPA-induced
      injury in rats up to 25 days of age, but becomes vulnerable to the toxicity by 32
      days of age. The basis for the resistance of the developing cerebellum to L-CPA
      is discussed.

PMID- 11305782
TI  - Is hyperthermia the triggering factor for hepatotoxicity induced by 3,4
      methylenedioxymethamphetamine (ecstasy)? An in vitro study using freshly isolated
      mouse hepatocytes.
AB  - The consumption of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) may cause
      hepatocellular damage in humans, a toxic effect that has been increasing in
      frequency in the last few years, although the underlying mechanisms are still
      unknown. The metabolism of MDMA involves the production of reactive metabolites
      which form adducts with intracellular nucleophilic sites, as is the case with
      glutathione (GSH). Also, MDMA administration elicits hyperthermia, a potentially
      deleterious condition that may aggravate its direct toxic effects. Thus, the
      objective of this study was to evaluate the extent of MDMA-induced depletion of
      GSH, induction of lipid peroxidation and loss of cell viability in freshly
      isolated mouse hepatocytes under normothermic conditions (37 degrees C) and to
      compare the results with the effects obtained under hyperthermic conditions (41
      degrees C). By itself, hyperthermia was an important cause of cell toxicity. A
      rise in incubation temperature from 37 degrees C to 41 degrees C caused oxidative
      stress in freshly isolated mouse hepatocytes, reflected as a time-dependent
      induction of lipid peroxidation and consequent loss of cell viability (up to 40
      45%), although the variations in GSH and GSSG levels were similar to those under
      normothermic conditions. MDMA (100, 200, 400, 800 and 1600 microM) induced a
      concentration- and time-dependent GSH depletion at 37 degrees C but had a
      negligible effect on lipid peroxidation and cell viability at this temperature.
      It is particularly noteworthy that hyperthermia (41 degrees C) potentiated MDMA
      induced depletion of GSH, production of lipid peroxidation and loss of cell
      viability (up to 90-100%). It is therefore concluded that hyperthermia
      potentiates MDMA-induced toxicity in freshly isolated mouse hepatocytes.

PMID- 11305783
TI  - Influence of metabolic activation on the induction of micronuclei by
      antihypertensive drugs in L929 cells.
AB  - The influence of metabolic activation on the genotoxic activity of the
      antihypertensive drugs hydralazine and dihydralazine was investigated. An in
      vitro micronucleus test for estimating the genotoxic activity of these drugs was
      used. The results obtained indicated that hydralazine and dihydralazine induce
      micronuclei formation in L929 cells. When L929 cell cultures were treated with
      drugs together with liver membrane fraction (S9 fraction) from polychlorinated
      biphenyl (Aroclor 1254) induced rat liver, the number of micronucleated cells
      decrease, however, almost to the level found in control cultures. The experiments
      with modified S9 mix allow the conclusion that the antioxidant enzymes catalase
      and superoxide dismutase present in S9 liver fraction play a role in the
      protection of cells from the genotoxic action of hydralazine and dihydralazine.

PMID- 11305784
TI  - Can molecular data place each neotropical monkey in its own branch?
AB  - Four different DNA datasets, representative of all extant neotropical primate
      genera, were tandemly aligned, comprising some 6,763 base pairs (bp) with 2,086
      variable characters and 674 informative sites. Maximum Parsimony, Maximum
      Likelihood and Neighbor-Joining analyses suggested three monophyletic families
      (Atelidae, Pitheciidae and Cebidae) that emerged almost at the same time during
      primate radiation. Combined molecular data showed congruent branching inside the
      atelid clade, placing Alouatta as the most basal lineage followed by Ateles and a
      more derived branch including Brachyteles and Lagothrix as sister groups. In the
      Pitheciidae, Callicebus was the most basal lineage with respect to Pithecia and
      to the more derived sister groups (Cacajao and Chiropotes). Conjoint analysis
      strongly supported the monophyly of the Cebidae, grouping Aotus, Cebus and
      Saimiri with the small callitrichines. Within callitrichines, Cebuella merged
      with Callithrix, Callimico appeared as a sister group of Callithrix/Cebuella,
      Leontopitecus as a sister group of the previous clade, and Saguinus was the
      earliest callitrichine offshoot. Two major points remained to be clarified in
      platyrrhine phylogeny: (i) the exact branching pattern of Aotus, Cebus, Saimiri
      and the callitrichines, and (ii), which two of these three families (Atelidae,
      Pitheciidae and Cebidae) are more closely related to one another.

PMID- 11305785
TI  - The accuracy of segregation of human mini-chromosomes varies in different
      vertebrate cell lines, correlates with the extent of centromere formation and
      provides evidence for a trans-acting centromere maintenance activity.
AB  - We show that the accuracy of mitotic segregation of three engineered, mapped
      human mini-chromosomes differs between human, mouse and chicken cell lines. We
      have studied the cause of these differences by analysing the extent of centromere
      formation on one mini-chromosome immunocytochemically. In human and chicken cell
      lines the mini-chromosomes segregate accurately and form centromeres but in one
      mouse cell line centromere formation is undetectable and mitotic segregation is
      inaccurate. These results indicate that the centromere is maintained by an
      activity that functions in trans and varies either in amount or specificity
      between different cells. Structurally defined mini-chromosomes may allow this
      activity to be studied.

PMID- 11305786
TI  - Expression and functional analysis of three isoforms of human heterochromatin
      associated protein HP1 in Drosophila.
AB  - Heterochromatin-associated protein 1 (HP1) is a nonhistone chromosomal protein
      associated with pericentromeric heterochromatin in Drosophila. HP1-like proteins
      have also been found associated with heterochromatin in human cells. The goal of
      this study was to determine whether proteins of the structurally conserved human
      HP1 family exhibit conserved heterochromatin targeting and silencing properties
      in Drosophila. We established transgenic lines of Drosophila melanogaster
      expressing each of the three human HP1 proteins, HP1Hsalpha, HP1HSbeta, and
      HP1Hsgamma, under the Hsp70 heat shock promoter. We show that all three isoforms
      of human HP1 are stably expressed in Drosophila and are associated with
      heterochromatin in Drosophila chromosomes. Like Drosophila HP1, all three human
      HP1 proteins are delocalized by an HP1-POLYCOMB chimeric protein, implying that
      both human HP1 and Drosophila HP1 interact in a common protein complex, and that
      at least some aspects of heterochromatin structure are highly conserved
      throughout the evolution of eukaryotes. Ectopic expression of two of the three
      human HP1 family proteins significantly enhances heterochromatic silencing in
      Drosophila.

PMID- 11305787
TI  - Nucleoplasmin binds to nuclear pore filaments and accumulates in specific regions
      of the nucleolar cortex.
AB  - Nucleoplasmin is a karyophilic protein that is involved in nucleosome formation
      and decondensation of chromatin, although other precise functions and modes of
      action of this molecule are still poorly understood. In the present paper we
      describe a novel nucleocytoplasmic transport assay that has enabled us to study
      the nuclear distribution of nucleoplasmin following its transport into the
      nucleus. Single Xenopus laevis oocyte nuclei were isolated and incubated with
      Xenopus egg extract containing colloidal gold-conjugated nucleoplasmin. After a
      period of incubation, each individual nucleus was processed for electron
      microscopy. The nuclear accumulation of nucleoplasmin was dependent upon the
      karyophilic properties of the protein, since BSA-conjugated gold particles did
      not enter the nuclear interior under the same experimental conditions. Once
      inside the nucleus, nucleoplasmin was detected in tracks emanating from the
      nuclear pores and reaching the nucleolus. Additionally, we found a striking
      accumulation of nucleoplasmin in specific areas of the nucleolar cortex. These
      perinucleolar regions were surrounded by areas of electron density similar to
      that of the fibrillar centers. Our results indicate that nucleoplasmin may play
      an important role in the transcription of ribosomal precursors. Moreover, this
      nucleocytoplasmic transport assay will enable the determination of the precise
      intranuclear localization of other karyophilic proteins.

PMID- 11305788
TI  - A broad replication origin of Drosophila melanogaster, oriDalpha, consists of AT
      rich multiple discrete initiation sites.
AB  - This work shows that the replication origin of Drosophila melanogaster,
      oriDalpha, consists of multiple discrete initiation sites. We attempted to map at
      high resolution the initiation sites in oriDalpha with a quantitative nascent DNA
      abundance assay using a competitive polymerase chain reaction (PCR) method.
      Nascent DNA was prepared from either cells blocked in very early S-phase and then
      labeled with 5-bromo-2'-deoxyuridine (BrdU), or asynchronously growing cells
      labeled briefly with BrdU. Denatured DNA was size-fractionated in alkaline
      sucrose gradients. BrdU-labeled nascent DNA was immuno-affinity purified using
      anti-BrdU antibodies. DNA was quantified with a competitive PCR method before and
      after immuno-purification. The results indicated that oriDalpha, whose size was
      presumed to be about 10 kb from two-dimensional gel electrophoretic analysis,
      contained four major initiation sites in its central 2.8 kb region, and six to
      approximately eight sites in 8.4 kb. All initiation sites corresponded with AT
      rich sequences. Detailed analysis of one major initiation site indicated that its
      range was restricted to 700 bp.

PMID- 11305789
TI  - Creating a new color by omission of 3 end blocking step for simultaneous
      detection of different chromosomes in multi-PRINS technique.
AB  - In the multiple color primed in situ labeling (multi-PRINS) technique, the
      blocking step using ddNTPs, incorporated by a DNA polymerase, is an important
      procedure that blocks the free 3' end generated in the previous PRINS reaction,
      thus avoiding the next PRINS reaction using it as a primer to perform spurious
      elongation at non-desired sites. However, we found that omission of the blocking
      step never affected the correct identification of two chromosomes because the
      signals from the second PRINS reaction site always showed the pure original
      color. Nevertheless, taking advantage of the color mixing, we successfully used a
      multi-PRINS technique to create a third color using the two most common forms of
      labeled dUTP (biotin- and digoxigenin-labeled dUTP) and two fluorochromes
      (fluorescein and rhodamine) in order simultaneously to detect three chromosomes
      in the same cell. By arranging the labeling either in bio-dig-bio or in dig-bio
      dig order in the sequential PRINS reaction, then detecting with a mixture of
      avidin-fluorescein/anti-dig-rhodamine or a mixture of anti-dig-fluorescein/avidin
      rhodamine, the signals at the centromeres of three different chromosomes
      displayed perfect yellow, red and green colors, respectively. The entire
      procedure could be completed in less than 90 min because the blocking step was
      omitted. We showed that this is a practical and efficient way to carry out
      multiPRINS so that even more than three chromosome targets could be detected in
      the same cell.

PMID- 11305790
TI  - The impact of the GH-IGF-I axis on gonadotropin secretion: inferences from animal
      models.
AB  - Given the tight, temporal coupling between growth and reproductive development,
      the idea that a common signal may regulate both adolescent growth and the
      initiation of puberty has been the focus of much research. Since the rate
      limiting step for the onset of puberty is the appropriate hypothalamic secretion
      of gonadotropin-releasing hormone (GnRH), any factor important for the initiation
      of puberty must affect GnRH pulsatility. This review examines the hypothesis that
      GH and/or IGF-I are growth-related signals that regulate the release of GnRH,
      initiating puberty. By extension, this review also addresses the hypothesis that
      the GH axis also impacts GnRH and gonadotropin secretion in post-pubertal
      individuals and, thus, affects the maintenance of fertility in adults. The review
      examines data from a range of animal models employing a number of different
      strategies which directly manipulate the activity of either GH or IGF-I. The
      success of these strategies for producing the desired effects on the GH-IGF-I
      axis is somewhat variable. Although IGF-I may only play a permissive role in the
      maintenance of adult fertility, acting at the level of the gonad to increase
      sensitivity to gonadotropin stimulation, the data indicate that IGF-I is
      essential for reproductive maturation. However, in addition to its well
      documented effects on the gonad, the specific mode of action of IGF-I on the
      neuroendocrine hypothalamus and GnRH pulsatility remains to be determined.
      Available evidence suggests that such action by IGF-I may be mediated through
      neurotransmitter effects on GnRH neurons, changing the availability of metabolic
      substrates for neuronal activity, or remodeling of synaptic input into GnRH
      neurons.

PMID- 11305791
TI  - Evidence for decreased growth hormone in patients with hypothalamic hamartoma due
      to Pallister-Hall syndrome.
AB  - Pallister-Hall syndrome (PHS) is characterized by hypothalamic hamartoma, bifid
      epiglottis, and central or postaxial polydactyly. Familial transmission is
      autosomal dominant; isolated cases also occur. To screen for hypothalamic
      pituitary dysfunction in PHS, we studied a 12 year-old boy (patient #1), and 14
      additional patients (patients #2-14: 7M, 7F; ages 4-72 yr). We performed serial
      sampling of GH, LH/FSH, TSH, and cortisol from 20.00-08 00 h. At 08.00 h, we
      measured IGF-I, peak responses of LH and FSH after GnRH, and cortisol after ACTH.
      We found that 6/7 children, including patient #1, and 6/8 adults had low or
      absent spontaneous GH secretion and/or low levels of IGF-I. Patient #1 also had
      accelerated pubertal development, but no other patient had abnormalities of the
      pituitary-gonadal axis, and none of the 14 patients had an abnormal thyroid or
      adrenal axis. We conclude that decreased pituitary GH secretion is common in PHS,
      and may exist in the absence of other forms of endocrine dysfunction.

PMID- 11305792
TI  - Insulin, insulin-like growth factors-I and -II and insulin-like growth factor
      binding protein-3 in newborn serum: association with normal fetal head growth and
      head circumference.
AB  - The insulin-like growth factors (IGF) and their binding proteins (IGFBP) have
      been implicated in the regulation of fetal weight and length. The aim of our
      study was to determine the relationship between head circumference at birth and
      serum levels of IGF-I, IGF-II, IGFBP-3 and insulin in full-term appropriate-for
      gestational age (AGA) infants. Serum samples were obtained from 77 singleton full
      term neonates, 69 AGA and 8 small-for-gestational age (SGA). The AGA infants were
      divided into three groups by head circumference: Group 1: < or = 3rd percentile;
      Group 2: at 50th percentile; Group 3: > or = 97th percentile. Serum levels of IGF
      I, IGF-II, IGFBP-3 and insulin were determined with commercial kits and
      immunometric methods. There were no statistically significant differences in mean
      serum levels of IGF-I, IGF-II and IGFBP-3 between the groups. A significantly
      higher mean serum insulin level was noted in the AGA infants with a head
      circumference > or = 97th percentile compared to those with a head circumference
      < or = 3rd percentile (4.6 +/- 0.3 vs 3.3 +/- 0.6 microU/ml; p = 0.04), and in
      AGA infants with a head circumference above the 50th percentile compared to those
      with a head circumference below the 50th percentile (4.4 +/- 0.4 vs 3.3 +/- 0.3
      microU/ml; p = 0.01). AGA infants with a head circumference above or below the
      50th percentile did not differ statistically in their mean IGF-II and IGFBP-3
      serum level, while IGF-I differed statistically between the groups (18 +/- 2.7 vs
      11.6 +/- 1.6 ng/ml, respectively; p = 0.045). Using univariate analysis, head
      circumference correlated positively with insulin (r = 0.29; p = 0.016) and with
      IGF-I (r = 0.26; p = 0.03). A stepwise multivariate linear regression analysis,
      however, did show statistically significant correlation of head circumference
      with birth weight (f = 36; p = 0.0001), and only marginally with birth length (f
      = 4.7; p = 0.06) and insulin (f = 3.4; p = 0.07). No correlations were found
      between head circumference and IGF-I, IGF-II or IGFBP-3. These data suggest that
      apart from genetic and nutritional factors, insulin may play a role in promoting
      intrauterine head growth, as reflected by head circumference at birth.

PMID- 11305793
TI  - Quantitative ultrasound measurements of bone strength in obese children and
      adolescents.
AB  - Very few studies have examined the effect of childhood obesity on bone
      mineralization. The purpose of the present study was to determine bone strength
      by quantitative ultrasound (QUS) measurements of bone speed of sound (SOS) in
      obese children (n = 45; age range 6-17 yr). SOS was measured (by Sunlight
      Omnisense) in the mid-tibial and radial bones. Data were compared to age- and
      gender-matched norms of Israeli non-obese children. Radial and tibial SOS was
      significantly reduced in obese compared to non-obese children (p < 0.05). Bone
      SOS in obese children with BMI > 95th percentile was not significantly different
      from obese children with BMI from 85-95th percentile. Tibial and radial SOS were
      correlated with pubertal stage (r = 0.52, p < 0.005; and r = 0.35, p < 0.01,
      respectively), and with chronological age (r = 0.47, p < 0.005; and r = 0.32, p <
      0.025, respectively). No significant correlation was found between endurance time
      as an indicator of fitness and bone SOS. Bone strength measured by QUS is reduced
      in obese children, but is not affected by the severity of obesity.

PMID- 11305794
TI  - Thyroid function and serum prolactin levels in patients with juvenile systemic
      lupus erythematosus.
AB  - OBJECTIVE: To evaluate both thyroid function and serum prolactin levels in
      patients with juvenile systemic lupus erythematosus (JSLE) and to detect possible
      correlation with disease activity. METHODS: Forty-two JSLE patients (3-15 years
      old at disease onset), twenty-two pubertal. All patients were evaluated according
      their clinical manifestations and disease activity. We determined serum
      prolactin, thyroid-stimulating hormone (TSH), T4, free T4, T3, thyroid
      peroxidasis and thyreoglobulin antibodies in all patients and controls. Thyroid
      ultrasonography was performed in the patients. RESULTS: We did not observe any
      difference in thyroid hormone and prolactin levels between patients and controls.
      One patient with JSLE presented with hyperthyroidism and six had thyroid
      antibodies. We observed abnormalities by ultrasonography in four patients (9.3%),
      specially heterogeneity of the gland echotexture. We did not find any correlation
      between prolactin levels, clinical manifestations or disease activity.
      CONCLUSIONS: Evaluation of thyroid function should not be routine for JSLE
      patients. Thyroid hormones and prolactin should be measured only in patients with
      clinical manifestations of hypo- or hyperthyroidism.

PMID- 11305795
TI  - Thyroid hormone profile in children with goiter in an endemic goiter area.
AB  - The thyroid hormone profile was investigated in goitrous schoolchildren aged 6-11
      years living in Antalya, an area with mild/ moderate iodine deficiency. With few
      exceptions, the serum levels of T4 and TSH were in the normal range in children
      with different grades of goiter. Compensatory elevated T3 levels were detected in
      24% of the subjects. Thyroid hormones did not differ significantly with respect
      to the urinary iodine (UI) level. No correlations were found between thyroid
      volume, UI excretion level and thyroid hormones. It was concluded that thyroid
      hormones, except compensatory T3 elevation in some subjects, were not affected
      significantly in a mild/moderate iodine deficient area.

PMID- 11305796
TI  - The clinical course of Hashimoto's thryoiditis in children and adolescents: 6
      years longitudinal follow-up.
AB  - Forty-six children and adolescents with Hashimoto's thyroiditis were followed up
      for 5.9 +/- 0.3 years. The mean age at diagnosis was 12.4 +/- 1.7 years (range 9
      15.4 yr). The patients were divided into three groups according to thyroid
      function: group 1 (n = 28) included patients who had normal concentrations of
      free thyroxine (FT4) and thyrotropin (TSH); group 2 (n = 8) included patients who
      had normal FT4 and elevated TSH, consistent with compensated hypothyroidism;
      group 3 (n = 10) included patients who had low FT4 and elevated TSH consistent
      with overt hypothyroidism. After 5.9 years of follow-up, four out of eight
      patients with compensated hypothyroidism had normal thyroid function and the
      other four patients developed overt hypothyroidism. Thyroxine therapy was
      administered in patients with overt hypothyroidism including the four patients
      with compensated hypothyroidism who later presented with overt hypothyroidism.
      All patients in both euthyroid and hypothyroid groups had normal growth and
      puberty. Final adult height was 0.43 +/- 0.80 SDS which was 1.58 +/- 3.03 cm
      above mid-parental height. The mean age at menarche (n = 43) was 12.4 +/- 1.1
      years, which was not different from normal children. The goiter remained the same
      size in most of the patients with euthyroidism without thyroxine therapy, but
      decreased in patients with overt hypothyroidism after thyroxine therapy.

PMID- 11305797
TI  - Association between serum leptin and anthropometric parameters at birth and at
      15th day of life in infants born asymmetrically small for gestational age.
AB  - The aim of this study was to investigate changes in skinfold measurements taken
      at three sites, mid-arm circumference and umbilical circumference during the
      first 15 days of life; and to evaluate relationships between anthropometric
      measurements and umbilical cord blood serum leptin levels in infants born small
      for gestational age (SGA) and appropriate for gestational age (AGA) infants. Of
      50 newborn infants, 25 were SGA and 25 were AGA. Neonates' weight, mid-arm
      circumference (MAC), umbilical circumference (UC), and triceps, subscapular and
      periumbilical skinfold thicknesses were measured (Holtain callipers) immediately
      after delivery. Anthropometric parameters were measured again at 15th days of
      age. At birth, mean birth weight, mean skinfold thickness, MAC and UC
      measurements in the AGA group were significantly higher than those of the SGA
      group. These differences were also found on the 15th day. Birth weight correlated
      with all skinfold thicknesses, MAC and UC at birth. Weight at 15th day of life
      correlated with skinfold thicknesses, MAC and UC at 15th day of life. Cord blood
      leptin level was significantly lower in the SGA than in the AGA infants. This
      difference continued on the 15th day. When cord blood leptin level was compared
      with that of the 15th day, we found that leptin levels in the cord blood were
      significantly higher. There were significantly positive correlations between
      leptin levels and birth weight and skinfold thicknesses when the infants were all
      grouped together. When the newborns were grouped according to birth weight, there
      were positive correlations between cord blood serum leptin levels and these
      parameters in the AGA group, but no correlation in the SGA group. At the 15th day
      of life serum leptin levels correlated with weight, subscapular and triceps
      skinfold thickness in the AGA group, but only with triceps skinfold thickness in
      the SGA group.

PMID- 11305798
TI  - Postprandial triglyceridemia in obese and non-obese adolescents. Importance of
      body composition and fat distribution.
AB  - BACKGROUND: It has recently been shown that obese adults have a disturbed
      metabolism of postprandial lipoproteins, resulting in postprandial
      hypertriglyceridemia. To the best of our knowledge, there are no data about
      postprandial triglyceridemia in obese and non-obese children and adolescents.
      SUBJECTS: 12 obese and 12 non-obese adolescents, aged 11.0 to 13.8 years.
      METHODS: Body composition and fat distribution (waist-to-hip circumference ratio
      and triceps/ subscapular skinfold thickness ratio) were assessed by
      anthropometry. An oral fat tolerance test was carried out, and fasting and
      postprandial lipid-lipoprotein serum concentrations were measured. RESULTS: We
      observed a significant increase in triglyceride serum concentrations 2 and 4
      hours after the oral fat load, in both obese and non-obese adolescents. In obese
      and non-obese adolescents there were significant correlations between some
      variables of postprandial lipemia and the studied indices of body fat
      distribution. When we compare postprandial lipemia in adolescents having a
      central pattern of fat distribution with those having a peripheral pattern of fat
      distribution, we observed higher variables related to postprandial lipemia in
      those having a central pattern of fat distribution compared with those with a
      peripheral pattern (sum of serum triglyceride concentrations: 6.06 vs 4.41, p =
      0.0243). CONCLUSIONS: We present a protocol to study postprandial lipemia in
      children and adolescents that allowed us to observe significant changes after an
      oral fat load. Results obtained indicate that the pattern of distribution of
      adipose tissue may be more important for lipid metabolism disturbances than total
      adipose tissue per se.

PMID- 11305799
TI  - A variation of vitamin D deficiency in children.
AB  - We report three children presenting with hypocalcemia, hyperphosphatemia,
      elevated levels of parathyroid hormone, low concentrations of 25(OH)-vitamin D,
      normal to elevated concentrations of 1,25(OH)2-vitamin D, and normal radiographs.
      Although these findings led to consideration of parathyroid hormone resistance,
      clinical and biochemical findings remained normal after discontinuation of
      therapy, suggesting a variation of vitamin D deficiency.

PMID- 11305800
TI  - Growth of children with primary hypothyroidism on treatment with respect to
      different ages at diagnosis.

PMID- 11305801
TI  - Effective growth hormone therapy in a growth hormone deficient patient with
      Duchenne muscular dystropy without evidence of acceleration of the dystrophic
      process.
AB  - We describe a patient with Duchenne muscular dystropy and growth hormone
      deficiency in whom treatment with human growth hormone for 2 years resulted in
      improved growth velocity without any detrimental effect on muscle strength.

PMID- 11305802
TI  - Two patients with Kabuki syndrome presenting with endocrine problems.
AB  - A 4 year-old boy with mental retardation and seizures presented to the pediatric
      endocrinology clinic because of a history of hypoglycemia; a 16 month-old girl
      with developmental delay presented with bilateral breast tissue enlargement; in
      both, a diagnosis of Kabuki syndrome was made because of typical facial features,
      neurodevelopmental delay and other stigmata consistent with Kabuki syndrome.
      Kabuki syndrome is a mental retardation-malformation syndrome affecting multiple
      organ systems with a broad spectrum of abnormalities. The facial features of the
      syndrome are specific and independent of ethnic origin. In addition to presenting
      with endocrine problems, the patients reported here exhibit some novel findings
      such as congenital alopecia areata and hyperpigmented skin lesion. The diagnosis
      of Kabuki syndrome should be considered in patients with hypoglycemia or
      premature thelarche when associated with developmental delay and a peculiar
      facies.

PMID- 11305803
TI  - Good metabolic control prevents post-surgical imbalance of mineral metabolism in
      patients with X-linked hypophosphatemic rickets.

PMID- 11305804
TI  - Elevated tissue factor circulating levels in children with hemolytic uremic
      syndrome caused by verotoxin-producing E. coli.
AB  - BACKGROUND: Microvascular thrombosis in the kidney plays an important role in the
      pathogenesis of hemolytic uremic syndrome (HUS). Tissue factor (TF), present on
      the vascular surface of endothelial cells, binds factor VIIa. The complex
      initiates the coagulating cascade by activating factors X and IX. PATIENTS AND
      METHODS: In cases of HUS associated with verotoxin-producing E. coli (VTEC)
      infection, VTEC gastroenteritis without HUS and normal controls, we measured
      plasma concentrations of TF and tissue factor pathway inhibitor (TFPI) to
      evaluate their clinical significance. In children with non-HUS chronic renal
      failure (CRF), the TF levels were also measured as another control group.
      RESULTS: In the acute phase of HUS, plasma levels of TF and TFPI were
      significantly elevated, then returned to normal range in the recovery phase. The
      TF levels were closely correlated with the thrombin antithrombin-III complex, a
      marker of thrombin activity in circulating blood, and with creatinine clearance
      (Ccr). Furthermore, a positive correlation was noted between plasma TF levels and
      plasma soluble thrombomodulin (sTM) levels, which is a marker of endothelial cell
      injury. The influence of decreased excretion from damaged kidneys should be
      considered since a definite lot correlation was observed between plasma TF levels
      and Ccr in children with non-HUS CRF. CONCLUSION: From these findings, we
      concluded that elevated TF circulating levels may also play an important role in
      blood-clotting activation observed in VTEC-HUS patients, and may also be a useful
      marker for renal damage.

PMID- 11305805
TI  - Distinct patterns of glomerular disease in Lima, Peru.
AB  - AIM: We performed both a retrospective and prospective study to elucidate the
      types of glomerular diseases present in adults in Lima, Peru. MATERIAL AND
      METHODS: In the retrospective study, we analyzed 1,263 renal biopsies over a 10
      year period (1985 -1995) that were processed at a central reference renal
      pathology laboratory in Lima. 101 cases were examined in the prospective study.
      RESULTS: The most common glomerular diseases observed were those due to systemic
      lupus erythematosus (30.2%), membranoproliferative glomerulonephritis (MPGN,
      14.8%), and focal and segmental glomerulosclerosis (FSGS, 13.9%). Although
      mesangial-proliferative nephritis was observed in 9.5% of cases, IgA nephropathy
      was rare (0.9%). Examination of the year to year frequency showed that MPGN has
      tended to decrease in frequency with time whereas FSGS has been increasing.
      Although there is known to be a high frequency of infections in Peru, only 4.2%
      of the cases in the retrospective study were associated with infection.
      Furthermore, in the prospective study, only one case of hepatitis C and no cases
      of hepatitis B viral infection were detected, including in the 11 cases of MPGN
      observed. CONCLUSION: We conclude that the epidemiology of glomerular disease in
      Lima, Peru, is distinct from most areas of the world, but has similarities to
      certain regions in Africa, in that MPGN is common whereas IgA nephropathy appears
      to be rare. Further studies are necessary to elucidate the reasons why the
      patterns of glomerular disease are different from that observed in other parts of
      the world.

PMID- 11305806
TI  - Detection of significant renal artery stenosis with color Doppler sonography:
      combining extrarenal and intrarenal approaches to minimize technical failure.
AB  - BACKGROUND: Renal artery disease can cause both hypertension and renal failure,
      and color Doppler sonography (CDS) may be a good screening method to detect it.
      Presently reported techniques of Doppler sonography have either a high rate of
      technical failure (4-42%), or low sensitivity and specificity, or detect only
      stenoses greater than 70%, or exclude patients with renal failure from analysis.
      In previous studies Doppler detection of renal artery stenosis (RAS) was based
      either on increased intrastenotic velocity or on the detection of post-stenotic
      Doppler phenomena. In the present prospective study these two approaches were
      combined to detect RAS (> or = 50% diameter reduction) in 226 consecutive
      patients (144 with normal and 82 with impaired renal function). METHODS: Stenosis
      of 50% or more was diagnosed if the maximal systolic velocity in the main renal
      artery was more than 180 cm/sec and velocity in the distal renal artery less than
      one quarter of the maximum velocity. When these velocities could not be
      determined a diagnosis of RAS was made when the acceleration time in intrarenal
      segmental arteries exceeded 70 msec. All patients subsequently underwent
      arteriography as the gold standard for the detection of RAS. RESULTS: With this
      combined approach, the technical failure rate of CDS was 0% in both patients with
      normal and those with impaired renal function. The mean time required for the
      Doppler investigation was 17 minutes. The sensitivity and specificity for
      detection of a significant stenosis in a given vessel (including accessory
      arteries), as compared to angiography, were 96.7% and 98.0%. CONCLUSION: Color
      Doppler sonography, evaluating both main renal and intrarenal arteries is an
      ideal screening method for detection of RAS of 50% or more because it allows
      accurate and rapid detection of stenosis in all patients, irrespective of renal
      function.

PMID- 11305807
TI  - Strategies and feasibility of hypertension control in a prevalent hemodialysis
      cohort.
AB  - BACKGROUND: There are few data to demonstrate the feasibility of long-term blood
      pressure (BP) control using short dialysis sessions as practiced in the US.
      Control of hypertension in hemodialysis patients may reduce the risk of
      cardiovascular events. METHODS: Forty-two dialysis patients had BPs and weights
      recorded before and after dialysis for two consecutive weeks and were followed by
      one physician over three years. Patients were treated by ultrafiltration and
      conventional antihypertensive drugs and BPs were repeated at three years in the
      32 survivors. RESULTS: 93% of the patients (39/42) were African-American. At
      inception, 85% of the patients were hypertensive with BPs of 154 +/- 23/83 +/- 14
      mmHg and 137 +/- 22/74 +/- 14 mmHg pre- and post-dialysis, respectively. The
      response to ultrafiltration was dependent upon gender, with women having a
      greater BP reduction compared to men. At three-year follow-up, the BP had dropped
      significantly in the survivors a mean of 9.4/6.7 mmHg. Pre- and post-dialysis
      weights, post dialysis BP and interdialytic weight-gain were unchanged. The BP
      reduction was achieved by an increase in the number of antihypertensive
      medications from 0.91 +/- 0.86 medications to 1.41 +/- 1.16. Improved BP control
      did not worsen the efficiency of dialysis (Kt/V). The use of beta-blockers
      doubled during the period of follow-up. Compared to the USRDS average
      cardiovascular death rate, the risk of cardiovascular deaths was improved 80%
      over three years. CONCLUSION: Long-term BP reduction can be achieved through the
      use of antihypertensive agents and volume control in a predominantly African
      American hemodialysis population. This may impact cardiovascular mortality.

PMID- 11305808
TI  - Optimal hematocrit for the maximum oxygen delivery to the brain with recombinant
      human erythropoietin in hemodialysis patients.
AB  - AIM: Although hematocrit (Ht) around 33 to 36% has been recommended, Ht of 30% is
      usually achieved as a target level during recombinant human erythropoietin
      (rHuEPO) therapy in the majority of hemodialysis (HD) patients. The present study
      aimed at estimating an optimal hematocrit (Ht) for the maximum oxygen delivery to
      the brain with rHuEPO. PATIENTS AND METHODS: Oxygen delivery was defined as a
      product of cerebral blood flow and arterial oxygen content (CaO2). The regional
      cerebral blood flow (rCBF) in each region of interest was measured by positron
      emission tomography and CaO2 was calculated from hemoglobin concentration,
      arterial oxygen saturation, and arterial oxygen tension before and after rHuEPO
      therapy (1,500 units, 3 times a week) in 5 HD patients (the mean age of 52 +/- 2
      (SEM) years old and the mean HD duration of 98 +/- 21 months). RESULTS: Ht rose
      significantly from 21 +/- 1 to 31 +/- 1% (p < 0.001) after the 3-month rHuEPO
      treatment in association with a significant increase in CaO2 from 7.7 +/- 0.4 to
      11.6 +/- 0.3 ml O2/100 ml (p < 0.01). Hemispheric rCBF decreased significantly
      from 40 +/- 3 to 32 +/- 1 ml/100 g/min (p < 0.02). In all data both before and
      after rHuEPO treatment, Ht inversely correlated with the hemispheric rCBF (y =
      55.7 - 0.76x, where y is rCBF and x is Ht, r = 0.80, p < 0.01), and positively
      with CaO2 (y = 0.85 + 0.34x, where y is CaO2 and x is Ht, r = 0.95, p < 0.01). By
      using these correlations, the hemispheric oxygen delivery was expressed as a
      function of Ht, being y = 47.3 + 18.3x - 0.3 x2, where y is cerebral oxygen
      delivery and x is Ht. From this curve, Ht at the highest cerebral oxygen delivery
      in the hemisphere, i.e. an optimal Ht was found to be 35.2%. Above this level of
      Ht, the hemispheric cerebral oxygen delivery would rather decline. CONCLUSION:
      The present study indicated that Ht of about 35% is required for a better oxygen
      delivery to the brain metabolism during anemia correction with rHuEPO.

PMID- 11305809
TI  - 24,25-dihydroxyvitamin D3 in combination with 1,25-dihydroxyvitamin D3
      ameliorates renal osteodystrophy in rats with chronic renal failure.
AB  - AIMS: This study compares the effects of 1,25(OH)2D3 and 24,25(OH)2D3 alone or in
      combination on renal osteodystrophy in rats with chronic renal failure (CRF).
      MATERIAL AND METHOD: One month subsequent to 5/6 nephrectomy animals were divided
      into four groups and treated for one or four weeks with either vehicle,
      1,25(OH)2D3, 24,25(OH)2D3 or 1,25(OH)2D3 + 24,25(OH)2D3. A sham-operated group
      with normal renal function matched for age and weight was used as control. At the
      termination of the study blood chemistry, parathyroid hormone (PTH) level and
      bone histomorphometry were analyzed. RESULTS: The main findings were:
      amelioration of 1,25(OH)2D3-induced hypercalcemia by 24,25(OH)2D3, and similar
      suppression of PTH by the two metabolites of vitamin D when administered alone or
      in combination. Bone histomorphometry showed that 1,25(OH)2D3 alone exerts a
      potent proliferative effect on the osteoblasts but severely depresses their
      mineralizing capacity in a dose- and time-dependent manner. By contrast,
      24,25(OH)2D3 improved the mineralizing activity with only a limited effect on
      osteoblast proliferation. Addition of 24,25(OH)2D3 potentiated the beneficial
      effect of 1,25(OH)2D3 on bone-resorbing parameters and corrected the
      mineralization failure. CONCLUSIONS: Based on the above observations we suggest
      that the combined treatment with 1,25(OH)2D3 and 24,25(OH)2D3 markedly improves
      the morphologic and metabolic abnormalities of renal osteodystrophy.

PMID- 11305810
TI  - Survival of vascular access during daily and three times a week hemodialysis.
AB  - AIM: A major cause of morbidity for hemodialysis patients is vascular access
      failure and/or occlusion. It is commonly believed that an increased frequency of
      dialysis sessions, among other factors, might lead to a higher rate of fistula
      complications. MATERIALS AND METHODS: To evaluate if patients on daily
      hemodialysis carry a higher risk of vascular access occlusion, we examined the
      incidence rate of access occlusion and the survival function of native vascular
      accesses in patients undergoing daily dialysis (DD; n = 24) as compared to
      patients on standard three times a week hemodialysis (TWD; n = 124). RESULTS: The
      mean follow-up time was 3.6 years. In the TWD group 42 patients had a first
      access closure, whereas only 2 patients out 24 had a similar event in the DD
      group. The proportion of first-access closure was 33.9% for TWD and 8.3% for DD
      (p < 0.01). The incidence rate was 9.8 (95% CI: 7.2 -13.2) and 2.2 (95% CI: 0.4 -
      7.1) events per 100 patient-years for TWD and DD, respectively. The rate
      difference was 7.6 (95% CI 3.4 - 11.9) events per 100 patient-years, and the
      unadjusted risk ratio was 4.5 (95% CI: 1.2 - 16.9; p < 0.01). The mean vascular
      access survival before closure was 3.3 years in TWD and 3.7 years in DD. Survival
      curves, obtained considering the first-access closure as the endpoint, showed a
      significant difference between DD and TWD (log-rank 5.16; p < 0.05). In a Cox
      proportional hazard model the relative risk (RR) of vascular-access closure in
      TWD remained significant (RR = 4.3; 95% CI 1.1 - 18.2) after adjustment for age.
      CONCLUSION: The results of this observational study, conducted on a limited
      number of DD patients, suggest that daily dialysis might not have an adverse
      prognostic significance for access closure.

PMID- 11305811
TI  - A pilot study of twin dialyzers in parallel to enhance delivered KT/V.
AB  - BACKGROUND: Adequacy of delivered dialysis is important in preventing morbidity
      in patients on hemodialysis for end-stage renal disease. A satisfactory KT/V is
      often difficult to obtain in patients with a large body mass despite optimization
      of remediable factors. AIM: This pilot study was performed to examine the
      hypothesis that twin dialyzers in parallel enhance delivered KT/V. METHODS: Three
      compliant patients on maintenance hemodialysis with post-dialysis weights greater
      than 95 kg who had a KT/V between 1.0 and 1.3 despite optimization of duration of
      dialysis, blood flow rates and anticoagulation and absence of access
      recirculation were studied using twin dialyzers in parallel after in vitro
      experiments demonstrated the safety of this technique. After a run-in period
      lasting over six months, during which the technique was perfected, three study
      treatments with twin dialyzers were compared to three treatments before and three
      treatments after study treatments. Both study and control treatments were
      performed under identical, rigidly standardized conditions. There was a wash-out
      period before the control and the study treatments. KT/V was calculated using the
      post-dialysis blood urea nitrogen (BUN) obtained by the stop-flow technique.
      RESULTS: KT/V was higher with twin dialyzers in parallel than with single
      dialyzers (mean +/- SD 1.54 +/- 0.32 for twin dialyzers vs 1.33 +/- 0.11 for
      single dialyzers) despite the lack of significant differences in potentially
      confounding variables. CONCLUSIONS: Using twin dialyzers in parallel appears to
      enhance delivered KT/V and is a safe and potentially useful technique especially
      in patients with a large body mass.

PMID- 11305812
TI  - Four cases of anti-myeloperoxidase antibody-related rapidly progressive
      glomerulonephritis during the course of idiopathic pulmonary fibrosis.
AB  - We report here 4 cases of rapidly progressive glomerulonephritis (RPGN) which
      developed during the management of idiopathic pulmonary fibrosis. In each
      patient, pulmonary disease preceded the onset of nephritis by 1 to 6 years. All
      patients had a high titer of serum autoantibodies against myeloperoxidase (MPO
      ANCA) when the diagnosis of RPGN was made. Although the association of pulmonary
      fibrosis with ANCA-related glomerulonephritis has been occasionally described in
      the past literature, the sequence of pulmonary and renal injury has not been well
      defined. The present report demonstrates that idiopathic pulmonary fibrosis
      exists as a preceding condition in some patients with MPO-ANCA-related nephritis.

PMID- 11305813
TI  - Membranous glomerulonephritis in a patient with inherited activated protein C
      resistance.
AB  - We present a patient with membranous glomerulonephritis, several clinical
      complications of the antiphospholipid syndrome and ulcerative colitis, but
      without lupus anticoagulant and antiphospholipid/cofactor antibodies.
      Immunological studies--other antibodies--were negative and failed to show enough
      criteria for any autoimmune diseases. Evaluation of her laboratory tests for
      hereditary thrombophilia revealed a heterozygous form of the Leiden mutation that
      might be associated with widespread vasculopathy. An interesting possibility is
      that the inherited activated protein C resistance could be an additional risk
      factor for vaso-occlusive manifestations appearing as a clinical sign of
      cardiovascular diseases and nephropathy.

PMID- 11305814
TI  - Chronic intestinal pseudo-obstruction due to dialysis-related amyloid deposition
      in the propria muscularis in a hemodialysis patient.
AB  - Dialysis-related amyloidosis (DRA) is one of the most serious complications
      interfering with rehabilitation in dialysis patients. Here, we report a case of
      beta2-microglobulin (beta2M)-related amyloidosis, in which the patient developed
      a severe intestinal pseudo-obstruction. The patient was a 42-year-old male who
      had been undergoing hemodialysis for 13 years, and who had no history of
      osteoarticular involvement of DRA. The first symptoms of the disease were severe
      abdominal fullness and nausea after meals. The whole intestinal wall biopsy
      revealed massive amyloid deposition in the propria muscularis. The patient became
      malnourished and died of acute subendocardial infarction 3 years after the onset.
      An autopsical examination revealed a massive deposition of amyloid, which was
      positively stained with anti-beta2M antibody but not AA amyloid, predominantly in
      the gastrointestinal muscular layer, including the tongue, esophagus, stomach,
      small intestines, colon, and rectum. These results suggest that the
      gastrointestinal involvement of beta2M-related amyloidosis might occur during the
      course of hemodialysis treatment, and that this possibility should be considered
      if patients suffer from intestinal pseudo-obstruction without osteoarticular
      symptoms.

PMID- 11305815
TI  - Efficacy of hemodiafiltration in a child with severe lactic acidosis due to
      thiamine deficiency.
AB  - We report the case of a child in whom severe lactic acidosis (LA) and
      hyperammonemia developed after twenty days of total parenteral nutrition (TPN)
      for diffuse esophageal damage due to caustic ingestion. The revision of TPN
      preparation revealed that thiamine was never included and the hypothesis of
      thiamine deficiency was later confirmed measuring the serum thiamine level.
      Because severe metabolic acidosis the dialytic treatment with hemodiafiltration
      (HDF) and bicarbonate infusion were performed: the patient very quickly recovered
      with dramatic reestablishment of the acid-basic balance. Thiamine administration
      restored lactate metabolism. We emphasize that HDF is a useful and prompt
      treatment for LA to get over the critical phase of neurological and cardiological
      damage.

PMID- 11305816
TI  - Successful management of polyneuropathy associated with IgM gammopathy of
      undetermined significance with antibody-based immunoadsorption.
AB  - Peripheral polyneuropathies associated with monoclonal IgM gammopathy of
      undetermined significance often have a progressive course and optimal treatment
      has not been established. We report on a patient diagnosed with polyneuropathy
      associated with benign IgM gammopathy, who was successfully treated with antibody
      based immunoadsorption only. The neurological symptoms of the patient improved
      continuously over six months of treatment. Controlled trials should be performed
      to define this indication for antibody-based immunoadsorption therapy.

PMID- 11305817
TI  - A reply to Reval et al.

PMID- 11305818
TI  - RPA defines minimal frequency for nephrologist/ESRD-dialysis patient contact.

PMID- 11305819
TI  - Optimizing obstetrical suite staffing: it's more than mathematics.

PMID- 11305820
TI  - Walking spinals: a myth or reality?

PMID- 11305821
TI  - Validity and reliability of undergraduate performance assessments in an
      anesthesia simulator.
AB  - PURPOSE: To examine the validity and reliability of performance assessment of
      undergraduate students using the anesthesia simulator as an evaluation tool.
      METHODS: After ethics approval and informed consent, 135 final year medical
      students and 5 elective students participated in a videotaped simulator scenario
      with a Link-Med Patient Simulator (CAE-Link Corporation). Scenarios were based on
      published educational objectives of the undergraduate curriculum in anesthesia at
      the University of Toronto. During the simulator sessions, faculty followed a
      script guiding student interaction with the mannequin. Two faculty independently
      viewed and evaluated each videotaped performance with a 25-point criterion-based
      checklist. Means and standard deviations of simulator-based marks were determined
      and compared with clinical and written evaluations received during the rotation.
      Internal consistency of the evaluation protocol was determined using inter-item
      and item-total correlations and correlations of specific simulator items to
      existing methods of evaluation. RESULTS: Mean reliability estimates for single
      and average paired assessments were 0.77 and 0.86 respectively. Means of
      simulator scores were low and there was minimal correlation between the checklist
      and clinical marks (r = 0.13), checklist and written marks (r = 0.19) and
      clinical and written marks (r = 0.23). Inter-item and item-total correlations
      varied widely and correlation between simulator items and existing evaluation
      tools was low. CONCLUSIONS: Simulator checklist scoring demonstrated acceptable
      reliability. Low correlation between different methods of evaluation may reflect
      reliability problems with the written and clinical marks, or that different
      aspects are being tested. The performance assessment demonstrated low internal
      consistency and further work is required.

PMID- 11305822
TI  - Perioperative intravenous flurbiprofen reduces postoperative pain after abdominal
      hysterectomy.
AB  - PURPOSE: To assess whether perioperative intravenous administration of
      flurbiprofen, a non-steroidal anti-inflammatory drug, reduced postoperative pain
      after abdominal hysterectomy. METHODS: Forty-five patients undergoing abdominal
      hysterectomy were randomly assigned to one of three groups of equal size. A
      control group (CONT) received a placebo 30 min before and at the end of surgery.
      The other two groups, PRE and POST, received 1 mg x kg(-1) flurbiprofen iv 30 min
      before and at the end of surgery, respectively. All patients received identical
      general and epidural anesthesia. Postoperatively, 50 mg diclofenac pr was given
      for pain relief on patient demand. One of the authors assessed pain using a 10 cm
      visual analog scale at rest and during coughing at the first request for
      diclofenac, and at 15, 24, 48, and 72 hr after surgery. The number of times
      diclofenac was required during the first 24 hr after surgery was also recorded.
      RESULTS: The number of diclofenac requests in the PRE (1.8 +/- 0.4) and POST
      groups (2.0 +/- 0.4) were less than in the CONT group (3.0 +/- 0.4). The PRE
      group showed lower visual analog scale at rest at 15 and 24 hr and on coughing at
      24, 48, and 72 hr after surgery than the CONT and POST groups. CONCLUSION:
      Intravenous 1 mg x kg(-1) flurbiprofen administered during anesthesia reduces
      postoperative rescue analgesic requirement after abdominal hysterectomy.
      Moreover, flurbiprofen is more effective when given before than after surgery.

PMID- 11305823
TI  - Dopexamine hydrochloride does not modify hemodynamic response or tissue
      oxygenation or gut permeability during abdominal aortic surgery.
AB  - PURPOSE: To assess the effects of intraoperative infusion of dopexamine (a DA-1
      and B2 adrenoreceptor agonist) on hemodynamic function, tissue oxygen delivery
      and consumption, splanchnic perfusion and gut permeability following aortic cross
      clamp and release. METHODS: In a randomised double blind controlled trial 24
      patients scheduled for elective infrarenal abdominal aortic aneurysm repair were
      studied in two centres and were assigned to one of two treatment groups. Group I
      received a dopexamine infusion starting at 0.5 microg x kg(-1) x min(-1)
      increased to 2 microg x kg(-1) x min(-1) maintaining a stable heart rate; Group
      II received a placebo infusion titrated in the same volumes following induction
      of anesthesia. Measured and derived hemodynamic data, tissue oxygen delivery and
      extraction and gut permeability were recorded at set time points throughout the
      procedure. RESULTS: Dopexamine infusion (0.5 -2 microg x kg x min(-1)) was
      associated with enhanced hemodynamic function (MAP 65 +/- 5.5 vs 92 +/- 5.7 mm
      Hg, P = <0.05) only during the period of aortic cross clamping. However, during
      the most part of infrarenal abdominal aortic surgery, dopexamine did not reduce
      systemic vascular resistance index, mean arterial pressure nor oxygen extraction
      compared with the control group. The lactulose/ rhamnose permeation ratio was
      elevated above normal in both groups (0.22 and 0.29 in groups I and II
      respectively). CONCLUSIONS: Dopexamine infusion (0.5 -2 microg x kg(-1) x min(
      1)) did not enhance hemodynamic function and tissue oxygenation values during
      elective infrarenal abdominal aortic aneurysm repair.

PMID- 11305824
TI  - Combined pre- and post-surgical bupivacaine wound infiltrations decrease opioid
      requirements after knee ligament reconstruction.
AB  - PURPOSE: To test the efficacy of a combination of selective pre- and post
      surgical local anesthetic infiltrations of the knee, compared with standard intra
      articular injection at the end of surgery alone, to reduce postoperative opioid
      requirements following arthroscopic cruciate ligament reconstruction (ACLR).
      METHODS: In a double-blind, randomized, controlled trial, we studied 23 patients
      (ASA I or II) scheduled for elective ACLR under general anesthesia. The treatment
      group (n = 12) received infiltrations with bupivacaine 0.25% with epinephrine
      1:200,000 presurgically (10 ml into the portals, 10 ml at the medial tibial
      incision site, 10 ml at the lateral femoral incision site, and 10 ml intra
      articularly) and postsurgically (5 ml at the medial tibial incision and 10 ml at
      the lateral femoral incision). The control group (n = 11) received infiltrations
      with saline 0.9% in the same manner. All patients received a standard intra
      articular local anesthetic instillation of the knee (25 ml of bupivacaine 0.25%
      with epinephrine 1:200,000) at the completion of surgery. RESULTS: Postoperative
      opioid requirements were lower in the treatment group (5.8 +/- 2.9 mg morphine
      equivalent) than in the control group ( 13.7 +/- 5.8 mg; P = 0.008). Treatment
      patients were ready for discharge approximately 30 min earlier than control
      patients (P = 0.046). There were no adverse events in the treatment group. In the
      control group, 2/11 patients vomited and a third experienced transient
      postoperative diaphoresis, dizziness and pallor. CONCLUSION: We conclude that a
      combination of selective pre- and post-surgical wound infiltration with
      bupivacaine 0.25% provides superior analgesia compared with a standard post
      surgical intra-articular injection alone.

PMID- 11305825
TI  - Complement split products and pro-inflammatory cytokines in salvaged blood after
      hip and knee arthroplasty.
AB  - PURPOSE: To determine whether salvaged autologous blood collected postoperatively
      contains complement split products (SC5b-9), and pro-inflammatory cytokines (IL-6
      and IL-8) and whether there are any differences between blood collected during
      hip or knee surgery. METHODS: Fifty-eight consecutive patients undergoing hip or
      knee replacement surgery were studied. Thirty-eight had postoperative bleeding
      large enough to require infusion of salvaged blood. The salvaged blood was
      filtered during collection through a 200 microm filter and before infusion a 40
      microm filter was used. Samples for complement and cytokine determinations were
      drawn from the circulation and from the collected blood. RESULTS: High
      concentrations of SC5b-9, IL-6, and IL-8 were found in salvaged blood. The
      concentrations were higher than in the circulation (P < 0.05). The circulating
      concentrations of IL-6 and IL-8 were increased 60 min and 12-18 hr after
      transfusion. There were no differences regarding SC5b-9, IL-6, and IL-8 in the
      blood collected after hip or knee surgery. CONCLUSION: Blood collected from a
      surgical wound contains large concentrations of inflammatory mediators. There
      were no differences between blood collected during hip or knee surgery.

PMID- 11305826
TI  - Selective spinal anesthesia for outpatient laparoscopy. I: characteristics of
      three hypobaric solutions.
AB  - PURPOSE: To determine the characteristics and recovery profiles of three
      hypobaric spinal anesthetic solutions. METHODS: Thirty outpatients undergoing
      outpatient laparoscopy were randomly assigned to receive spinal anesthesia with
      one of three small-dose solutions. Group I--20 mg lidocaine plus 25 microg
      fentanyl; Group II--20 mg lidocaine plus 10 microg sufentanil; Group III--10 mg
      lidocaine plus 10 microg sufentanil. Solutions were diluted to three ml with
      sterile water for injection. A 27-gauge Whitacre needle was inserted at L2-3 or
      L3-4 in the sitting position. Sensory and motor recovery were assessed with
      pinprick, proprioception, light touch and a modified Bromage scale. RESULTS:
      Operating conditions were good to excellent in all three groups. The incidence of
      shoulder tip discomfort, pruritus and nausea was not significantly different
      between groups. Light touch was present in all three groups and proprioception
      was present in most patients during and after surgery. Group III patients had a
      more rapid recovery of pinprick analgesia and Group II patients had the slowest
      recovery of pinprick analgesia. Motor block recovery was comparable in the three
      groups. Eighty percent of patients in Groups III and I were able to perform 'deep
      knee bends' and 'straight leg raises' at the end of surgery. CONCLUSION: For
      short duration laparoscopy, spinal 10 mg lidocaine with 1O microg sufentanil
      provided selective pin prick analgesia, with preserved touch, proprioception and
      limited motor block. Operating conditions were satisfactory and most patients
      were able to fulfill 'walk out' criteria at the end of surgery.

PMID- 11305827
TI  - Selective spinal anesthesia for outpatient laparoscopy. II: epinephrine and
      spinal cord function.
AB  - PURPOSE: To compare two small-dose solutions (with and without epinephrine) for
      spinal anesthesia during outpatient laparoscopy and to determine spinal cord
      function with these low-dose solutions. METHOD: Twenty outpatients undergoing
      gynecological laparoscopy were randomly assigned to receive spinal anesthesia
      with one of two low dose solutions. Group LS-10 mg lidocaine plus 10 microg
      sufentanil; Group LSE-10 mg lidocaine plus 10 microg sufentanil plus epinephrine
      50 microg. Solutions were diluted to three millilitres with sterile water for
      injection. A 27-gauge Whitacre needle was inserted at L2-3 or L3-4 in the sitting
      position. Operating conditions and spinal cord function (spinothalamic, dorsal
      column and motor) were assessed. RESULTS: Operating conditions were good
      excellent in both groups. The incidence of shoulder tip discomfort, pruritus and
      nausea, and the amount of supplementation with alfentanil and midazolam was not
      different between groups. Most patients in both groups had preserved dorsal
      column function and normal motor power on arrival in PACU and were able to
      satisfy 'walk out' criteria. Recovery of pinprick sensation and discharge times
      were not different. Mild pruritus (VAS score < or = 5) was present in both
      groups. CONCLUSION: For short duration laparoscopy, addition of 50 microg
      epinephrine to a small dose of spinal 10 mg lidocaine with 10 microg sufentanil
      did not provide additional benefit in terms of intraoperative analgesia or
      operating conditions. Spinal cord function was preserved with small-dose
      techniques.

PMID- 11305828
TI  - Selective spinal anesthesia for outpatient laparoscopy. III: sufentanil vs
      lidocaine-sufentanil.
AB  - PURPOSE: The efficacy of low dose intrathecal lidocaine-sufentanil was compared
      with intrathecal sufentanil for short duration outpatient gynecological
      laparoscopy. METHODS: Thirteen ASA I and II patients undergoing gynecological
      laparoscopy were studied in a randomized double-blind trial. Patients received
      either intrathecal 10 mg lidocaine plus 10 microg sufentanil (Group LS) or
      intrathecal 20 microg sufentanil (Group S), each diluted to 3 mL with sterile
      water through a 27g Whitacre needle in the sitting position. Sensory and motor
      recovery were assessed with pinprick and a modified Bromage scale. RESULTS: One
      of seven Group LS patients and two of five Group S patients required conversion
      to general anesthesia for failed skin test with forceps. Two of the remaining
      three Group S patients felt sharpness with skin incision. The study was
      terminated early because of inadequate anesthesia in Group S. The small sample
      size (n = 9) made statistical analysis uninformative. CONCLUSION: Intrathecal 20
      microg sufentanil is unsuitable as a sole agent for gynecological laparoscopy.

PMID- 11305829
TI  - Selective spinal anesthesia for outpatient laparoscopy. IV: population
      pharmacodynamic modelling.
AB  - PURPOSE: To apply a population pharmacodynamic model to small-dose hypobaric
      spinal anesthesia for outpatient laparoscopy. METHODS: The level of spinal
      analgesia after spinal blockade with small-dose (20-25 mg) hypobaric lidocaine
      was assessed by means of pinprick in patients undergoing outpatient laparoscopy.
      In 57 patients, 385 measurements were available for analysis. We first modelled
      the data for each patient with a mixed-effects model described by Schnider (Model
      1). The population mean parameters, inter-individual variance, and residual
      variance were estimated. Clinically important endpoints (time to reach T10
      (onset), time to maximal level, duration and maximally attained level) of each
      patient were calculated based on the estimated time course of analgesia level for
      each patient. The model was used to predict the later data with respect to level
      of spinal analgesia of each patient from fits based on the observed data in the
      first 75 min. RESULTS: The mean +/- SD onset time was 8.3 +/- 1.9 min, time to
      maximal level was 20.8 +/- 5.3 min, duration of effect was 37.9 +/- 13.1 min, and
      mean maximal level was T5. There was a good correlation (R2 = 0.90) between the
      observed levels of analgesia and those predicted from the model. Data from the
      first 75 min predicted the later observed data for each patient moderately well
      (R2 = 0.38). CONCLUSION: A population pharmacodynamic model was applied to low
      dose hypobaric lidocaine spinal anesthesia. Clinically important endpoints were
      determined and forecasting of later data with respect to level of spinal
      analgesia was attempted. Such an approach may be useful in the management of low
      dose spinal anesthetic techniques in outpatients.

PMID- 11305830
TI  - Selective spinal anesthesia for outpatient laparoscopy. V: pharmacoeconomic
      comparison vs general anesthesia.
AB  - PURPOSE: To compare the cost and effectiveness of small-dose spinal anesthesia
      (SP) with general anesthesia (GA) for outpatient laparoscopy. METHODS: A
      retrospective record analysis of 24 patients who received SP were compared with
      28 patients who received GA in our Daycare centre. The costs of anesthesia and
      recovery were calculated, from an institutional perspective, using 1997 Canadian
      Dollar values. Effectiveness was measured in terms of time for anesthesia and
      recovery, and postoperative antiemetic and analgesic requirements. RESULTS: Both
      groups were well matched for age, weight, duration and type of surgery. The mean
      total cost for the SP group of $53.45 +/- 10.40 was no different from that for
      the GA group of $48.92 +/- 10.25 (95% CI -10.3, 1.2). Time to administer
      anesthesia was longer in the SP group with a mean time of 18 +/- 8 min compared
      with 10 +/- 3 min in the GA group (CI -11.3, -4.7). Recovery time in the PACU was
      longer in the SP group 123 +/- 51 min compared with 94 +/- 48 min (CI -56.6,
      1.4). Postoperative antiemetic requirements were similar: 8% in SP group vs 14%
      in GA group, whereas analgesic requirements were less in the SP group with 25%
      receiving analgesia compared with 75% in the GA group (P < 0.05). CONCLUSION: The
      total cost of anesthesia and recovery using SP is similar to that for GA when
      used for outpatient laparoscopy. Spinal anesthesia was less effective than GA in
      time to administer anesthesia and in duration of recovery. Postoperative
      analgesic requirements were reduced using SP.

PMID- 11305831
TI  - Premedication modifies the quality of sedation with propofol during regional
      anesthesia.
AB  - PURPOSE: To determine the effects of diazepam or clonidine on the quality of
      sedation with propofol during regional anesthesia. METHODS: In a prospective
      randomised, controlled, double-blinded study, 60 patients undergoing elective
      gynecological surgery were studied. They were given premedication with 0.15-mg
      clonidine (Group-CL, n=20), 5-mg diazepam (Group-DZ, n = 20), or placebo (Group
      P, n = 20) po. After spinal anesthesia was established, sedation was provided
      with propofol and controlled using a five-point sedation score at 3, "eyes closed
      but rousable to command", and 4, "eyes closed but rousable to mild physical
      stimulation". During sedation, blinded anesthesiologist recorded occurrence of
      complications. At two hours after end of sedation, patients were asked if they
      had intraoperative dream and memory. RESULTS: The loading dose, steady-state
      infusion rate, and overall mean infusion rate in Group-CL were 0.80 mg x kg(-1),
      2.35 mg x kg(-1) x hr(-1) and 2.89 mg x kg(-1) x hr(-1), compared with 0.97 mg x
      kg(-1), 3.13 mg x kg(-1) x hr(-1) and 3.59 mg x kg(-1) x hr(-1) in Group-DZ, and
      1.38 mg x kg(-1), 4.10 mg x kg(-1) x hr(-1) and 4.36 mg x kg(-1) x hr(-1) in
      Group-P, respectively. Indices of both Group-CL (P < 0.001) and Group-DZ (P <
      0.05) were smaller than those of Group-P Moreover, clonidine reduced the
      incidence of uncontrolled movement (P < 0.01), while diazepam reduced the
      incidence of intraoperative memory and increased the incidence of dream (P <
      0.05). Premedication did not affect the incidence of other complications.
      CONCLUSION: Both premedicants reduced propofol requirements and exerted
      beneficial effects on the incidence of some complications during sedation with
      propofol as an adjunct to regional anesthesia.

PMID- 11305832
TI  - Synergistic analgesic effects of intrathecal midazolam and NMDA or AMPA receptor
      antagonists in rats.
AB  - PURPOSE: To investigate the interaction of midazolam and N-methyl-D-aspartate
      (NMDA) receptor or -amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA)
      receptor antagonist on the effects of persistent inflammatory nociceptive
      activation. METHODS: Male Sprague-Dawley rats were implanted with lumbar
      intrathecal catheters and were tested for their responses to subcutaneous
      formalin injection into the hindpaw. Saline, midazolam (1 to 100 microg), AP-5 (I
      to 30 microg), a NMDA receptor antagonist, or YM872 (0.3 to 30 microg), an AMPA
      receptor antagonist was injected intrathecally 10 min before formalin injection.
      The combinations of midazolam and AP-5 or YM872 in a constant dose ratio based on
      the 50% effective dose (ED50) were also tested and were analysed with an
      isobologram. RESULTS: Dose-dependent effects were observed with midazolam (ED50
      was 1.34 microg and 1.21 microg in phase 1 and 2 of the formalin test,
      respectively), AP-5 (7.64 microg and 1.4 microg) and YM872 (0.24 microg and 0.21
      microg). Synergistic effects in both phases were obtained when combining
      midazolam with AP-5 or YM872. The ED50 of midazolam decreased to 0.012 microg
      (phase 1) and 0.27 microg (phase 2) with AP-5 and to 0.09 microg (phase 1) and
      0.35 microg (phase 2) with YM872 (P < 0.01). CONCLUSIONS: These results suggest a
      functional coupling of benzodiazepine-aminobutyric acid (GABA)A receptor with
      NMDA and AMPA receptors in acute and persistent inflammatory nociceptive
      mechanisms in the spinal cord.

PMID- 11305833
TI  - Optimal number of beds and occupancy to minimize staffing costs in an obstetrical
      unit?
AB  - PURPOSE: We describe how the science of analyzing patient arrival and discharge
      data can be used to determine the optimal number of staffed OB beds to minimize
      labour costs. METHODS: The number of staffed beds represents a balance between
      having as few staffed beds as possible to care properly for parturients vs having
      enough capacity to assure available staff for new admissions. The times of
      admission and discharge of patients from the OB unit can be used to calculate an
      average census. From this average census, and the properties of the Poisson
      distribution, the optimal number of staffed beds can be estimated. This
      calculation requires specification of the risk of having all in-house and on-call
      staff caring for patients, such that additional staff are unavailable should
      another parturient arrive. As an example, patient admission and discharge times
      were obtained for 777 successive patients cared for at an obstetrical unit. The
      numbers of patients present in the OB unit each two-hour period were calculated
      and analyzed statistically. PRINCIPAL FINDINGS: There was variation in the
      average census among hours of the day and days of the week. Poisson distributions
      fit the data for each of four periods throughout the week. Simply benchmarking
      the current average occupancy and comparing it to a desired occupancy would have
      been inadequate as this neglected consideration of the risk of being unable to
      appropriately care for an additional patient. CONCLUSIONS: The optimal number of
      beds and occupancy of an OB unit to minimize staffing costs can be determined
      using straightforward statistical methods.

PMID- 11305834
TI  - Postpartum postural headache due to superior sagittal sinus thrombosis mistaken
      for spontaneous intracranial hypotension.
AB  - PURPOSE: To describe a case of superior sagittal sinus thrombosis in the
      puerperal period and the difficulties encountered in the diagnosis and
      management. CLINICAL FEATURES: A 29-yr-old multiparous woman presented with a
      postural headache four weeks after a normal pregnancy and vigorous delivery.
      Initial presentation suggested spontaneous intracranial hypotension (SIH) since
      there was no history of epidural or spinal anesthesia, or trauma or surgery to
      her back or neck. Conservative therapy was initially offered and then a lumbar
      epidural blood patch (LEBP) was performed, although it failed to relieve the
      postural headache. A dural leak could not be demonstrated but an MRV (magnetic
      resonance venography) revealed a superior sagittal sinus thrombosis (SSST).
      Although anticoagulant therapy was immediately initiated, the neurologist
      remained convinced that the postural headache was secondary to SIH, and,
      consequently, a second epidural blood patch was requested. Anesthesia was
      reluctant to perform an LEBP at this point and suggested continuing
      anticoagulation until a subsequent MRV demonstrated recannalization of the SSST.
      This advice was followed and the postural headache resolved spontaneously with
      intravenous anticoagulation. CONCLUSION: The present case illustrates the
      importance of a multidisciplinary approach to the management of this rare
      complication of pregnancy. This case also highlights the importance of reviewing
      the differential diagnosis when considering treatment of a postural headache in
      the puerperium.

PMID- 11305835
TI  - Asystole after intravenous neostigmine in a heart transplant recipient.
AB  - PURPOSE: To describe a heart transplant recipient who developed asystole after
      administration of neostigmine which suggests that surgical dennervation of the
      heart may not permanently prevent significant responses to anticholinesterases.
      CLINICAL FEATURES: A 67-yr-old man, 11 yr post heart transplant underwent left
      upper lung lobectomy. He developed asystole after intravenous administration of 4
      mg neostigmine with 0.8 mg glycopyrrolate for reversal of the muscle relaxant. He
      had no history of rate or rhythm abnormalities either prior to or subsequent to
      the event. CONCLUSION: When administering anticholinesterase medications to heart
      transplant patients, despite surgical dennervation, one must be prepared for a
      possible profound cardiac response.

PMID- 11305836
TI  - Pulmonary edema in the neuroradiology suite: a diagnostic dilemma.
AB  - PURPOSE: To present the case of an initially unexplained complication of sudden
      pulmonary edema in a patient during stenting of the carotid artery in the
      interventional neurology suite. CLINICAL FEATURES: A 46-yr-old woman (ASA III)
      having an intracavernous carotid artery angioplasty and stenting procedure under
      neurolept anesthesia developed sudden pulmonary edema on completion of an
      otherwise uneventful stenting procedure. The patient responded well to initial
      management of pulmonary edema although the cause of the edema remained unclear.
      On retrospective examination of data and with the evolution of clinical signs it
      became apparent that the patient had suffered a subarachnoid hemorrhage which
      eventually resulted in her death. CONCLUSIONS: Clinical signs of intracerebral
      events may be slow to evolve. The cause of sudden pulmonary edema in patients
      undergoing an interventional neuroendovascular procedure is likely to be
      neurogenic in origin despite the initial lack of neurological signs.

PMID- 11305837
TI  - Cochrane Anesthesia Review Group.

PMID- 11305838
TI  - Intermittent fluid drip suggests misplacement of central venous catheter into the
      interpleural space.

PMID- 11305839
TI  - High epidural block with chloroprocaine in a parturient with low
      pseudocholinesterase activity.

PMID- 11305840
TI  - TOF monitoring is required to achieve effective transient neuromuscular blockade
      in ICU patients.

PMID- 11305841
TI  - Pulmonary carbon dioxide embolism during laparoscopic cholecystectomy.

PMID- 11305842
TI  - Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients.
AB  - In clinical trials of dopamine-blocking antipsychotics, significant adverse
      events may occur in healthy volunteers at dose levels that are well tolerated by
      schizophrenic patients. Because of these differences in tolerability,
      bioequivalence and pharmacokinetic studies of antipsychotics should be performed
      in schizophrenic patients rather than in healthy volunteers. When clozapine is
      the drug being investigated, pharmacokinetic and bioequivalence studies should be
      carried out in real-life dosage conditions because the half-life of clozapine
      increases with multiple doses. Under real-life conditions, the evaluation of
      multiple doses of clozapine in a population of schizophrenic patients can provide
      direct therapeutic relevance to bioavailability findings. This article discusses
      patient recruitment and informed consent in pharmacokinetic trials of
      schizophrenia, issues in studying antipsychotic agents in healthy volunteers
      versus schizophrenic patients, and a bioequivalency study of Clozaril (Novartis
      Pharmaceuticals) and generic clozapine (Creighton [Sandoz]) in schizophrenic
      patients.

PMID- 11305843
TI  - Clinical effects of a randomized switch of patients from clozaril to generic
      clozapine.
AB  - INTRODUCTION: Clozapine was discovered in 1959 but withheld from the United
      States market after several deaths due to agranulocytosis. The medication was
      approved in the United States in 1989 on a compassionate-use basis and was first
      marketed in 1990 as Clozaril. In 1999, following approval by the U.S. Food and
      Drug Administration, Zenith Goldline Pharmaceuticals (ZGP) introduced a generic
      form of clozapine. METHOD: After 5 weeks of data collection (phase I), 24
      patients were randomly assigned to group A and 21 patients to group B. Patients
      had DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder
      with psychosis, or atypical psychosis with mood disorder. In phase II, group A
      received a mean daily dose of 630 mg of generic clozapine, and group B continued
      to receive Clozaril at a mean daily dose of 610 mg, each for 8 weeks. In phase
      III, group A was reassigned to Clozaril, and group B was switched to generic
      clozapine, each for 8 weeks. At the end of phase III, group B resumed Clozaril.
      Efficacy was measured with the Clinical Global Impressions-Improvement (CGI-I)
      scale, the Brief Psychiatric Rating Scale (BPRS), and the Beck Depression
      Inventory (BDI). RESULTS: Five patients experienced relapse when they were
      switched from Clozaril to generic clozapine. Eleven patients worsened short of
      full relapse, 9 while receiving ZGP generic clozapine and 2 while receiving
      Clozaril. CGI-I scores and BPRS scores favored patients receiving Clozaril
      significantly. Only BDI scores favored patients receiving generic clozapine
      significantly. CONCLUSION: Until more studies have been performed, clinicians and
      administrators should carefully monitor stable Clozaril-treated patients who are
      being switched to generic clozapine.

PMID- 11305844
TI  - Branded versus generic clozapine: bioavailability comparison and
      interchangeability issues.
AB  - Clozapine has been the treatment of choice for patients with refractory
      schizophrenia. Generic clozapine has recently become available, because of a
      waiver of the usual criteria for establishing bioequivalence. However, there are
      biopharmaceutical, bioavailability, and clinical concerns related to the generic
      formulation raised by both clinicians and academic researchers. We conducted a
      prospective, randomized, crossover study to evaluate steady-state
      pharmacokinetics, pharmacodynamics, and tolerability of generic clozapine (Zenith
      Goldline Pharmaceuticals) versus Clozaril (Novartis Pharmaceuticals) in
      schizophrenic patients. A preliminary report of the pertinent bioavailability
      results is presented here. Despite comparable mean plasma concentration-time
      curves, significant differences were found in the primary pharmacokinetic
      parameters of the 2 formulations in almost 40% of patients. Such intraindividual
      differences raise the issue of average bioequivalence versus individual
      bioequivalence and the implication for interchangeability of different clozapine
      formulations. The decision to switch a patient from branded to generic clozapine
      should be made on an individual basis with special emphasis on clinical outcome,
      and patients should be monitored closely during the transition.

PMID- 11305845
TI  - Comparison of the bioequivalence of generic versus branded clozapine.

PMID- 11305846
TI  - United States Food and Drug Administration requirements for approval of generic
      drug products.
AB  - As generic products become more available for the treatment of psychiatric
      disorders, clinicians must stay abreast of the U.S. Food and Drug Administration
      (FDA) requirements for the approval of generic drug products. The FDA declares
      that pharmaceutical equivalents only are therapeutically equivalent, and
      pharmacokinetic data are all that is usually required to determine therapeutic
      equivalence. The rationale behind the overall concept of bioequivalence is that
      if 2 pharmaceutical equivalents provide identical plasma concentration-time
      profiles in humans, there is no evidence to demonstrate that the 2 identical
      dosage forms will exhibit a difference in safety and efficacy. This article
      reviews current terminology used in abbreviated new drug applications for generic
      products, typical bioequivalence study designs, and FDA bioequivalence guidance
      for clozapine.

PMID- 11305847
TI  - Duration of untreated psychosis: a critical examination of the concept and its
      importance.
AB  - BACKGROUND: The concept of duration of untreated psychosis (DUP) has recently
      attracted much interest because of its possible relationship to treatment outcome
      and implications for preventive efforts with reference to psychotic disorders,
      especially schizophrenia. In this paper we review critically the literature
      concerning the concept and its importance. METHODS: Articles concerned with
      measuring DUP and those that have been suggested to provide indirect or direct
      evidence of the effect of DUP on treatment outcome are reviewed. RESULTS:
      Evidence thus far suggests that DUP may be related to ease of reducing psychotic
      symptoms once treatment begins for first episode patients, but there is no
      evidence of a relationship to likelihood of relapse. There has been little
      investigation of the relationship of DUP to other long-term outcomes such as
      negative symptoms and cognitive functioning neither have the possible confounds
      of DUP been widely investigated or controlled. CONCLUSIONS: It is important that
      there should be more thorough investigations of DUP, its correlates, and the
      extent to which it does mediate any advantages of earlier intervention.

PMID- 11305848
TI  - Life events and depression in a community sample of siblings.
AB  - BACKGROUND: The overall aim of the GENESiS project is to identify quantitative
      trait loci (QTLs) for anxiety/depression, and to examine the interaction between
      these loci and psychosocial adversity. Here we present life-events data with the
      aim of clarifying: (i) the aetiology of life events as inferred from sibling
      correlations; (ii) the relationship between life events and measures of anxiety
      and depression, as well as neuroticism; and (iii) the interaction between life
      events and neuroticism on anxiety/depression indices. METHODS: We assessed the
      occurrence of one network and three personal life-event categories and multiple
      indices of anxiety/depression including General Health Questionnaire, Anhedonic
      Depression, Anxious Arousal and Neuroticism in a large community-based sample
      of2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw
      ordinal maximum likelihood were used to estimate within-individual and between
      sibling correlations of life events. The relationship between life events and
      indices of emotional states and personality were assessed by multiple linear
      regression and canonical correlations. RESULTS: Life events showed sibling
      correlations of 0-37 for network events and between 0-10 and 0.19 for personal
      events. Adverse life events were related to anxiety and depression and, to a less
      extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism,
      anxiety and depression) accounted for 11% and life events for 3% of the variance
      in emotional states. There were no interaction effects. CONCLUSIONS: Life events
      show moderate familiality and are significantly related to symptoms of anxiety
      and depression in the community. Appropriate modelling of life events in linkage
      and association analyses should help to identify QTLs for depression and anxiety.

PMID- 11305849
TI  - Monozygotic twins discordant for major depression: a preliminary exploration of
      the role of environmental experiences in the aetiology and course of illness.
AB  - BACKGROUND: Genetic effects upon behaviour are pervasive. To what extent are the
      many correlates of major depression (MD) due to individual-specific environmental
      experiences versus genetic factors correlated with risk for MD? METHODS: From a
      population-based twin registry, we identified 72 female monozygotic pairs
      discordant for a lifetime history of MD and compared the affected and unaffected
      members on a wide range of putative correlates of MD. RESULTS: The affected twin
      differed from her unaffected co-twin on many variables, eight of which were
      maximally discriminating: (i) maternal protectiveness; (ii) conflictual parent
      child relationship; (iii) low optimism; (iv) current stressful life events; (v)
      financial difficulties and a history of (vi) phobia, (vii) nicotine dependence;
      and (viii) divorce. A cluster analysis suggested three 'environmental pathways'
      to MD characterized by: (i) childhood vulnerability and anxiety; (ii) acting-out
      and demoralization; and (iii) interpersonal difficulties. CONCLUSION: Important
      precursors and sequelae of MD originate in environmental experiences unique to
      the individual and are not mediated through genetic factors or family-of-origin
      effects. Such environmental factors cause pervasive differences in monozygotic
      twins discordant for MD, especially in the areas of interpersonal difficulties,
      psychopathology, social problems and self-concept. These findings should be
      interpreted in the context of possible retrospective recall bias and the
      difficulty of distinguishing risk factors from sequelae in co-twin-control
      studies.

PMID- 11305850
TI  - No evidence of increased risk for schizophrenia or bipolar affective disorder in
      persons with aneuploidies of the sex chromosomes.
AB  - BACKGROUND: Several case reports and reviews have suggested an increased
      incidence of schizophrenia or bipolar disorder among persons with sex chromosome
      aneuploidies, but this observation may have been caused by biased sampling.
      METHODS: The 1122 individuals with sex chromosome aneuploidies registered in the
      Danish Cytogenetic Central Register were screened in the Danish Psychiatric
      Central Register for admissions with schizophrenia or bipolar affective disorder.
      Both registers are population based and have existed since 1968 and 1969
      respectively. Relative risks were calculated for schizophrenia, bipolar affective
      disorder and either schizophrenia or bipolar disorder combined as one phenotype.
      Since hospitalization for a psychiatric disorder increases the probability that a
      cytogenetic examination is performed, the relative risks could be inflated, and
      they were therefore adjusted accordingly. RESULTS: Aneuploidies of the X or Y
      chromosomes were not associated with an increased risk of schizophrenia or
      bipolar disorder. The occurrence of the combined phenotype including both
      schizophrenia and bipolar disorder was significantly reduced among persons with
      Turner's syndrome and significantly increased among individuals with the 47, XYY
      karyotype. CONCLUSIONS: This population-based study did not find evidence
      supporting the presence of risk alleles for schizophrenia or bipolar disorder on
      the X chromosome or the pseudoautosomal region on the Y chromosome. The findings
      of an increased risk for the combined phenotype to XYY males and the reduced risk
      for persons with Turner's syndrome are interesting but difficult to explain with
      present neurobiological knowledge and inconsistent with the other findings of the
      study.

PMID- 11305851
TI  - Depression, APOE genotype and subjective memory impairment: a cross-sectional
      study in an African-Caribbean population.
AB  - BACKGROUND: Subjective memory impairment (SMI) is common in older populations but
      its aetiology and clinical significance is uncertain. Depression has been
      reported to be strongly associated with SMI. Associations with objective
      cognitive impairment are less clear cut. Other factors suggested to be associated
      with SMI include poor physical health and the apolipoprotein E (APOE) epsilon4
      allele. Studies of SMI have been predominantly confined to white Caucasian
      populations. METHOD: A community study was carried out in a UK African-Caribbean
      population aged 55-75, sampled from primary care lists. Twenty-three per cent
      were classified with SMI. Depression was defined using the 10-item Geriatric
      Depression Scale. Other aetiological factors investigated were education,
      objective cognitive function, APOE genotype, disablement and vascular
      disease/risk. The principal analysis was restricted to 243 participants scoring >
      20 on the Mini-Mental State Examination (85%). A second analysis included all 290
      participants. RESULTS: Depression, self-reported physical impairment and APOE
      epsilon4 were associated with SMI. The association between SMI and physical
      impairment was not explained by depression, vascular disease/risk, or
      disability/handicap. The association between epsilon4 and SMI increased as MMSE
      scores decreased and was particularly strong in those with depression. The
      epsilon4 allele was present in 69% (95% CI 41-89%) of those with depression and
      SMI compared with 28% (20-36%) of those with neither. CONCLUSIONS: Depression may
      not be a sufficient explanation for subjective memory complaints. Memory
      complaints in the presence of depression are associated with high prevalence of
      epsilon4 and therefore, presumably, a raised risk of subsequent dementia.

PMID- 11305852
TI  - Memory complaints as a precursor of memory impairment in older people: a
      longitudinal analysis over 7-8 years.
AB  - BACKGROUND: There is considerable dispute about the validity of memory
      complaints. While some studies find that complaints are an early indicator of
      dementia or cognitive decline, there are also many studies showing that
      complaints are more closely associated with negative affect (depression, anxiety
      and neuroticism). The present paper used three-wave longitudinal data to test
      three hypotheses: (1) that memory complaints reflect an evaluation of present and
      past memory performance; (2) that memory complaints predict future memory
      performance; and (3) that memory complaints predict current and future negative
      affect. METHODS: A longitudinal study was carried out with a community sample of
      people aged 70 and over. Participants were assessed for memory complaints, memory
      performance and negative affect at three waves separated by 3.6 years and 4.0
      years. There were 331 persons with data on all relevant variables. The data were
      analysed using structural equation modelling. RESULTS: Significant paths in the
      structural model were found from memory performance to future memory complaints,
      as well as from memory complaints to future memory performance, supporting
      hypotheses 1 and 2. Memory complaints were associated with current negative
      affect, but did not predict future negative affect. CONCLUSIONS: Memory
      complaints do reflect perceptions of past memory performance and are also an
      early manifestation of memory impairment. However, current negative affect
      (anxiety and depression symptoms) shows the greatest association with memory
      complaints.

PMID- 11305853
TI  - The NART as an index of prior intellectual functioning: a retrospective validity
      study covering a 66-year interval.
AB  - BACKGROUND: The National Adult Reading Test (NART) is widely used in research and
      clinical practice as an estimate of pre-morbid or prior ability. However, most of
      the evidence on the NART's validity as a measure of prior intellectual ability is
      based on concurrent administration of the NART and an IQ measure. METHOD: We
      followed up 179 individuals who had taken an IQ test (the Moray House Test) at
      age 11 and administered the NART and the Mini-Mental State Examination (MMSE) at
      age 77. A subset (N = 97) were also re-administered the original IQ test.
      RESULTS: The correlation between NART performance at age 77 and IQ age 11 was
      high and statistically significant (r = 0.73; P < 0001). This correlation was
      comparable to the correlation between NART and current IQ, and childhood IQ and
      current IQ, despite the shared influences on the latter variable pairings. The
      NART had a significant correlation with the MMSE but this correlation fell to
      near zero (r = 0.02) after partialling out the influence of childhood IQ.
      DISCUSSION: The pattern of results provides strong support for the claim that the
      NART primarily indexes prior (rather than current) intellectual ability.

PMID- 11305854
TI  - A pilot study of cognitive therapy in bipolar disorders.
AB  - BACKGROUND: The efficacy and effectiveness of cognitive therapy (CT) is well
      established for unipolar disorders, but little is known about its utility in
      bipolar disorders. This study aimed to explore the feasibility and efficacy of
      using CT as an adjunct to usual psychiatric treatment in this patient population.
      METHOD: Subjects referred by general adult psychiatrists were assessed by and
      independent rater and then randomly allocated to immediate CT (N = 21) or 6-month
      waiting-list control, which was then followed by CT (N = 21). Observer and self
      ratings of symptoms and functioning were undertaken immediately prior to CT,
      after a 6-month course of CT and a further 6-months later. Data on relapse and
      hospitalization rates in the 18 months before and after commencing CT were also
      collected. RESULTS: At 6-month follow-up, subjects allocated to CT showed
      statistically significantly greater improvements in symptoms and functioning as
      measured on the Beck Depression Inventory, the Internal State Scale, and the
      Global Assessment of Functioning than those in the waiting-list control group. In
      the 29 patients who eventually received CT, relapse rates in the 1 8 months after
      commencing CT showed a 60 % reduction in comparison with the 18 months prior to
      commencing CT. Seventy per cent of subjects who commenced therapy viewed CT as
      highly acceptable. CONCLUSION: Although the results of this study are
      encouraging, the use of CT in subjects with bipolar disorders is more complex
      than in unipolar disorders and requires a high level of therapist expertise. The
      therapy may prove to be particularly useful in the treatment of bipolar
      depression.

PMID- 11305855
TI  - Discriminating between chronic fatigue syndrome and depression: a cognitive
      analysis.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) and depression share a number of
      common symptoms and the majority of CFS patients meet lifetime criteria for
      depression. While cognitive factors seem key to the maintenance of CFS and
      depression, little is known about how the cognitive characteristics differ in the
      two conditions. METHODS: Fifty-three CFS patients were compared with 20 depressed
      patients and 38 healthy controls on perceptions of their health, illness
      attributions, self-esteem, cognitive distortions of general and somatic events,
      symptoms of distress and coping. A 6 month follow-up was also conducted to
      determine the stability of these factors and to investigate whether CFS-related
      cognitions predict ongoing disability and fatigue in this disorder. RESULTS:
      Between-group analyses confirmed that the depressed group was distinguished by
      low self-esteem, the propensity to make cognitive distortions across all
      situations, and to attribute their illness to psychological factors. In contrast,
      the CFS patients were characterized by low ratings of their current health
      status, a strong illness identity, external attributions for their illness, and
      distortions in thinking that were specific to somatic experiences. They were also
      more likely than depressed patients to cope with their illness by limiting stress
      and activity levels. These CFS-related cognitions and behaviours were associated
      with disability and fatigue 6 months later. CONCLUSIONS: CFS and depression can
      be distinguished by unique cognitive styles characteristic of each condition. The
      documented cognitive profile of the CFS patients provides support for the current
      cognitive behavioural models of the illness.

PMID- 11305856
TI  - The relationship between obsessive-compulsive disorder and anxiety and affective
      disorders: results from the Johns Hopkins OCD Family Study.
AB  - OBJECTIVE: This study investigates the relationship of specific anxiety and
      affective disorders to obsessive-compulsive disorder (OCD) in a blind, controlled
      family study. METHOD: Eighty case and 73 control probands, as well as 343 case
      and 300 control first-degree relatives of these probands, participated in the
      study. Subjects were examined by psychologists or psychiatrists using the
      Schedule for Affective Disorder and Schizophrenia-Lifetime Anxiety version (SADS
      LA). Two experienced psychiatrists independently reviewed all clinical materials,
      and final diagnoses were made according to DSM-IV criteria, by consensus
      procedure. RESULTS: Except for bipolar disorder, all anxiety and affective
      disorders investigated were more frequent in case than control probands.
      Substance dependence disorders were not more frequent. Generalized anxiety
      disorder (GAD), panic disorder, agoraphobia, separation anxiety disorder (SAD)
      and recurrent major depression were more common in case than control relatives.
      These disorders occurred more frequently if the relative was diagnosed with OCD.
      Only GAD and agoraphobia were more frequent in case relatives independent of OCD.
      CONCLUSION: GAD and agoraphobia share a common familial aetiology with OCD. The
      other anxiety and affective disorders, when comorbid with OCD, may emerge as a
      consequence of the OCD or as a more complex syndrome.

PMID- 11305857
TI  - The context of delusional experiences in the daily life of patients with
      schizophrenia.
AB  - BACKGROUND: Global characteristics and psychosocial risk factors related to
      delusions have been identified. The present study extends these findings to the
      level of everyday functioning, identifying characteristics of delusional moments
      (DMs) and contextual risk and protective factors for delusional exacerbations in
      daily life. METHODS: Data were collected using the Experience Sampling Method
      (ESM), a time-sampling technique. Forty-eight chronic patients diagnosed with
      schizophrenia rated the intensity of pathological symptoms and mood states and
      described their thoughts and the environmental context during consecutive moments
      in daily life. Delusions were defined on the basis of self-rated suspicion,
      preoccupation, feeling controlled, and coded thought pathology. Daily context
      included current activity, persons present and location. Characteristics of DMs
      and non-delusional moments (nDMs) were compared, and a multilevel logistic
      regression model was used to identify contexts that might trigger or prevent DMs.
      RESULTS: On average, patients experienced delusions less than one-third of the
      time. DMs were characterized by higher negative affect and lower positive affect.
      The presence of family or acquaintances decreased the risk of subsequently
      experiencing a DM, whereas withdrawal from activities increased this risk.
      CONCLUSIONS: Data support the validity of ESM for investigating delusions in
      schizophrenia. Daily life contexts appear to alter the probability that delusions
      will occur. Knowledge about such contexts may therefore be useful in helping
      patients develop better coping strategies and in creating therapeutic
      interventions that can lessen emotional distress.

PMID- 11305858
TI  - Face processing in schizophrenia: defining the deficit.
AB  - BACKGROUND: Abnormalities of face affect naming and face recognition occur in
      schizophrenia but it is not clear whether the deficits reflect wider underlying
      impairments of perception, memory, language or executive function. METHOD: Twenty
      six patients with schizophrenia were compared with 23 healthy volunteers on
      neuropsychological tests and tests of face and affect processing. Face and non
      face tests were compared at four levels of processing: visuo-spatial perception,
      recognition memory, language and naming, and executive function. We examined
      relationships with drug dose, duration of illness and pre-morbid and current IQ.
      RESULTS: Patients and controls did not differ in estimated pre-morbid IQ but
      current IQ was 12 points lower in patients. At each level of processing there
      were correlated deficits of face and non-face processing in the patients that
      were mostly independent of IQ decline. Impaired face and non-face visuo-spatial
      function and recognition performance were generally correlated with drug dose.
      Impairments in naming face emotions were correlated with other non-face naming
      tasks independently of drug dose. Patients performed less well than controls in
      classifying faces by emotion while ignoring identity and this was associated with
      poorer performance in Wisconsin Card Sorting. CONCLUSIONS: The pattern of results
      suggests that deficits in face processing reflect three wider neuropsychological
      impairments: a drug-related impairment of visual imagery, and disease-related
      impairments of semantic retrieval and executive function.

PMID- 11305859
TI  - Patients' and relatives' assessment of clozapine treatment.
AB  - BACKGROUND: Subjective evaluations by schizophrenic patients and their relatives
      of clozapine treatment were assessed as part of an exploratory study. METHODS: A
      problem-centred interview was carried out with 80 patients at discharge from in
      patient or day-hospital treatment. Views of 46 relatives on the treatment were
      also assessed. RESULTS: In addition to expected effects (improvement of or
      stabilisation of one's state of mental health, antipsychotic effects), patients
      surprisingly often highlighted the calming and relaxing effect of clozapine as
      well as improved sleep as particularly positive. While more than half of the
      respondents expected a worsening of their condition if they stopped taking
      medication, only every fifth patient feared a relapse. Among the negative
      effects, fatigue and sedation were cited by far the most often. The absence of
      extrapyramidal side effects was clearly noted as an advantage of clozapine. Only
      10% of those questioned were aware of the risks for the haemotopoetic system
      associated with the drug. Differences were found between patients' and relatives'
      assessments particularly with regard to the negative effects. CONCLUSIONS:
      Patients and relatives frequently hold specific and distinct views on clozapine
      treatment. These views should be considered when patients and relatives are
      informed and when compliance is addressed.

PMID- 11305860
TI  - Stratum-specific likelihood ratios of two versions of the general health
      questionnaire.
AB  - BACKGROUND: In other branches of epidemiology, stratum specific likelihood ratios
      (SSLRs) have been found to be preferable to fixed best threshold approaches to
      screening instruments. This paper presents SSLRs of GHQ-12 and GHQ-28 and
      compares the SSLR method with the traditional optimal threshold approach.
      METHODS: Random effects meta-analysis and meta-regression were used to obtain
      pooled estimates of SSLRs of the two questionnaires for the 15 centres
      participating in the WHO study of Psychological Problems in General Health Care.
      We illustrated the use of SSLRs by applying them to random samples of patients
      from centres with different backgrounds. RESULTS: For developed and urban
      centres, the estimates of SSLRs were homogeneous for 10 out of 12 strata of the
      GHQ-12 and GHQ-28. For other centres, the overall results, which were
      heterogeneous for six out of 12 strata, were deemed the currently available best
      estimates. When we applied these results to centres with different prevalences of
      mental disorders and backgrounds, the estimates matched the actually observed
      closely. These examples showed how the SSLR approach is more informative than the
      traditional threshold approach. CONCLUSIONS: Those working in developed urban
      settings can use the corresponding SSLRs with reasonable confidence. Those
      working in non-urban or developing areas may wish to use the overall results,
      while acknowledging that they must remain less certain until further research can
      explicate heterogeneity. These SSLRs have been incorporated into nomograms and
      spreadsheet programmes so that future researchers can swiftly derive the post
      test probability for a patient or a group of patients from a pre-test probability
      and GHQ score.

PMID- 11305861
TI  - Predicting admission rates to secure forensic psychiatry services.
AB  - BACKGROUND: The planning and development of secure forensic psychiatry services
      for mentally disordered offenders in England and Wales has proceeded
      independently within different regional areas. However, certain mental disorders,
      offenders, and offending behaviour are all more prevalent in geographical areas
      characterized by socio-economic deprivation and social disorganization. Failure
      to consider these factors has led to inadequate service provision in some areas
      and inequity in funding. A new model is required to predict admissions to these
      services as an aid to resource allocation. METHOD: Actual admissions (N = 3155)
      to high and medium secure psychiatric services for seven of 14 (pre
      reorganization) Regional Health Authorities, 1988-94. Expected admissions were
      calculated for each district using 1991 census data adjusted for under
      enumeration. Standardized psychiatric admission ratios were calculated and a
      range of social, health status, and service provision data were used as
      explanatory variables in a regression analysis to determine variation between
      districts. RESULTS: Actual psychiatric admissions varied from 160% above to 62%
      below expected for age, sex, and marital status, according to patients' catchment
      area of origin, measured according to deciles of the distribution of
      underprivileged area scores at ward level. The most powerful explanatory
      variables included a composite measure of social deprivation, ethnicity and
      availability of low secure beds at regional level. CONCLUSION: Admission rates to
      secure forensic psychiatry services demonstrate a linear correlation with
      measures of socio-economic deprivation in patients catchment area of origin. A
      model was developed to predict admissions from District Health Authorities and is
      recommended for future use in resource allocation. Identification of factors that
      explain higher admission rates of serious offenders with mental disorder from
      deprived areas is a priority for future research.

PMID- 11305862
TI  - An experimental investigation of hypervigilance for threat in children and
      adolescents with post-traumatic stress disorder.
AB  - BACKGROUND: The present study examined biases in visual attention for emotional
      material in children and adolescents with post-traumatic stress disorder (PTSD)
      and healthy controls. METHODS: The participants carried out an attentional
      deployment task in which probe detection latency data were used to determine the
      distribution of visual attention for threat-related and depression-related
      material. RESULTS: The results showed that children and adolescents with PTSD,
      relative to controls, selectively allocated processing resources towards socially
      threatening stimuli and away from depression-related stimuli. This attentional
      avoidance of depression-related information in the PTSD participants declined
      with age. CONCLUSIONS: The results of the study are interpreted as a
      consolidation and extension of previous research on attentional bias and
      emotional disorder in younger participants.

PMID- 11305863
TI  - Seasonality of suicide in Singapore: data from the equator.
AB  - BACKGROUND: Studies in the northern and southern hemispheres consistently
      identify seasonal patterns in suicidal deaths. In many such studies, bimodal
      yearly peaks have been described for females as against unimodal ones for males.
      The current study examines the monthly variation in suicidal deaths in Singapore
      to determine if any seasonal patterns exist in an equatorial region. METHODS:
      Monthly suicidal death data over the decade 1989-98 were examined for the whole
      sample and for gender- and age-specific subgroups. Both von Mises' distribution
      and harmonic analysis techniques were used to interpret the data. RESULTS: Among
      the 2013 male and 1382 female suicides, there was minimal variation in patterning
      of suicidal deaths. We found a weak suggestion of a later peak for the females in
      mid-May as opposed to mid-February for the males, and the peaks for those less
      than 25 years of age were 5-6 months later than for the older age groups. The
      magnitude of all peaks was, however, very small suggesting chance variation. The
      harmonic analyses confirmed that patterning was 'randomly' rather than
      'seasonally' determined. CONCLUSION: In an equatorial region, there was no
      evidence of any 'seasonal' patterning of suicidal deaths.

PMID- 11305864
TI  - Post-traumatic stress disorder in primary-care settings: prevalence and
      physicians' detection.
AB  - BACKGROUND: Little is known about the prevalence of PTSD in primary-care settings
      and regarding the ability of primary-care physicians to detect PTSD. The current
      study examines prevalence of PTSD in a national sample of primary-care attenders
      and primary-care physicians' detection of PTSD and general psychological distress
      in PTSD patients. METHODS: Data are from a national study of 2975 primary-care
      attenders in Israel. Demographic data, responses to the GHQ-28, PTSD Inventory
      and physicians' diagnoses were examined. RESULTS: Twenty-three per cent of all
      patients who attended clinics (N = 684) reported traumatic events, 39% of whom
      (males 37%, females 40%) met criteria for PTSD on the PTSD Inventory. Eighty per
      cent of the males and 92% of the females with PTSD were distressed according to
      the GHQ. According to physicians, 37% of persons who reported trauma (40% of the
      women, 32% of the men) suffered from psychological distress. Only 2% of patients
      meeting PTSD criteria on the self-report measure were given a diagnoses of PTSD
      by physicians. CONCLUSIONS: Many primary-care patients suffer from PTSD, which is
      usually accompanied by major psychological distress. Attention by primary-care
      physicians to a history of trauma could improve physicians' detection of this
      disabling disorder.

PMID- 11305865
TI  - Is early bereavement or chronic depression associated with breast cancer?

PMID- 11305866
TI  - The Worster-Drought syndrome and other syndromes of dementia with spastic
      paraparesis: the paradox of molecular pathology.

PMID- 11305867
TI  - Production of MMPs in human cerebral endothelial cells and their role in shedding
      adhesion molecules.
AB  - Matrix metalloproteinases (MMPs) are Zn2+-endopeptidases that seem to play an
      important role in chronic inflammatory diseases of the central nervous system by
      disrupting the blood-brain barrier (BBB) and mediating the destruction of myelin
      components. We therefore investigated the influence of the pro-inflammatory
      cytokine TNF-alpha. on the expression and activation of several MMPs in human
      cerebral endothelial cells (HCEC). HCEC constitutively express MMP-2 and MMP-3
      mRNA, but only MMP-3 is upregulated on mRNA and protein level after TNF-alpha
      stimulation. MMP-9 and MMP-12 mRNA could only be detected under inflammatory
      conditions. Furthermore, MMPs are involved in shedding of cell surface molecules.
      We therefore investigated the influence of MMPs on the release of soluble
      adhesion molecules using marimastat, a specific broad-spectrum MMP inhibitor and
      other protease inhibitors like aprotinin or leupeptin. Only marimastat inhibited
      the TNF-alpha mediated release of sVCAM-1 in the supernatants of HCEC. Western
      blot results of culture supernatants supported the time dependent release of the
      complete extracellular portion of the VCAM-1 molecule. These data suggest that
      MMPs produced by HCEC are actively involved in the shedding of soluble adhesion
      molecules at the BBB.

PMID- 11305868
TI  - Frontal lobe dementia with novel tauopathy: sporadic multiple system tauopathy
      with dementia.
AB  - We present a novel tauopathy in a patient with a 10-yr history of progressive
      frontal lobe dementia and a negative family history. Autopsy revealed mild
      atrophy of frontal and parietal lobes and severe atrophy of the temporal lobes.
      There were occasional filamentous tau-positive inclusions, but more interesting
      were numerous distinctive globular neuronal and glial tau-positive inclusions in
      both gray and white matter of the neocortex. Affected subcortical regions
      included substantia nigra, globus pallidus, subthalamic nucleus, and cerebellar
      dentate nucleus, in a distribution similar to progressive supranuclear palsy
      (PSP), but without significant accompanying neuronal loss or gliosis.
      Predominantly straight filaments were detected by electron microscopy (EM), while
      other inclusions were similar to fingerprint bodies. No twisted ribbons were
      detected. Immuno-EM studies revealed that only the filamentous inclusions were
      composed of tau. Immunoblotting of sarkosyl-insoluble tau revealed 2 major bands
      of 64 and 68 kDa. Blotting analysis after dephosphorylation revealed
      predominantly 4-repeat tau. Sequence analysis of tau revealed that there were no
      mutations in either exons 9-13 or the adjacent intronic sequences. The unique
      cortical tau pathology in this case of sporadic multiple system tauopathy with
      dementia adds a new pathologic profile to the spectrum of tauopathies.

PMID- 11305869
TI  - Quantitation of apoE domains in Alzheimer disease brain suggests a role for apoE
      in Abeta aggregation.
AB  - Apolipoprotein E (apoE) and apoE-derived proteolytic fragments are present in
      amyloid deposits in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA).
      In this study, we examined which apoE fragments are most strongly associated with
      amyloid deposits and whether apoE receptor binding domains were present. We found
      that both apoE2- and apoE4-specific residues were present on plaques and blood
      vessels in AD and CAA. We quantified Abeta plaque burden and apoE plaque burdens
      in 5 AD brains. ApoE N-terminal-specific and C-terminal-specific antibodies
      covered 50% and 74% of Abeta plaque burden, respectively (p < 0.003). Double
      labeling demonstrated that the plaque cores contained the entire apoE protein,
      but that outer regions contained only a C-terminal fragment, suggesting a
      cleavage in the random coil region of apoE. Presence of N- and C-terminal apoE
      cleavage fragments in brain extracts was confirmed by immunoblotting. The numbers
      of plaques identified by the apoE N-terminal-specific antibodies and the apoE C
      terminal-specific antibody were equal, but were only approximately 60% of the
      total Abeta plaque number (p < 0.0001). Analysis of the size distribution of
      Abeta and apoE deposits demonstrated that most of the Abeta-positive, apoE
      negative deposits were the smallest deposits (less than 150 microm2). These data
      suggest that C-terminal residues of apoE bind to Abeta and that apoE may help aid
      in the progression of small Abeta deposits to larger deposits. Furthermore, the
      presence of the apoE receptor binding domain in the center of amyloid deposits
      could affect surrounding cells via chronic interactions with cell surface apoE
      receptors.

PMID- 11305870
TI  - Oxidative stress and disturbed glutamate transport in hereditary nucleotide
      repair disorders.
AB  - Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA
      repair disorders complicated by progressive neurodegeneration. Here we
      immunohistochemically examine the in situ expression of materials that are
      produced by oxidative stress and glutamate transporters (which can contribute to
      prevention of glutamate neurotoxicity) in the brains of 5 autopsied patients each
      of XPA, CS, and control groups. All oxidative products, including nitrotyrosine,
      advanced glycation end product, and 4-hydroxy-2-nonenal-modified protein (HNE)
      were deposited in large amounts in the globus pallidus of CS patients compared to
      XPA patients. They were frequently recognized in the pseudocalcified foci and
      free minerals in the neuropil, and more rarely in foamy spheroids. In addition,
      the deposition of HNE was observed also in hippocampal and cerebellar dentate
      neurons of both CS and XPA patients. The expression of glial glutamate
      transporters, EAAT1 and GLT-1, was affected in the globus pallidus in 5 CS
      patients and 3 XPA patients. They were also altered in the cerebellar cortex in
      most of the CS patients. These data suggest that oxidative stress and disturbed
      glutamate transport may be involved in pallidal and/or cerebellar degeneration in
      hereditary nucleotide repair disorders.

PMID- 11305871
TI  - Neurofibrillary pathology in transgenic mice overexpressing V717F beta-amyloid
      precursor protein.
AB  - Overexpression of mutated human amyloid precursor protein (hAPP717V-->F) under
      control of the platelet-derived growth factor promoter (PDAPP minigene) in
      transgenic (tg) mice results in plaque formation and astroglial activation
      similar to Alzheimer disease (AD). However, the extent of the neurofibrillary
      pathology in this model is less understood. In order to determine if these mice
      develop AD-like neurofibrillary pathology, vibratome sections from PDAPP tg mice
      (4- to 20-months-old) were immunolabeled with antibodies against phosphorylated
      tau (AT8) and phosphorylated neurofilaments (SMI 312, TA51), and analyzed by
      laser scanning confocal and electron microscopy. Phosphorylated neurofilament
      immunoreactive dystrophic neurites in plaques were first seen in mice at 10 to 12
      months of age, while phosphorylated tau-immunoreactive dystrophic neurites were
      observed after 14 months of age. Immunoelectron microscopic analysis revealed
      that phosphorylated neurofilament immunoreactivity was diffusely distributed
      along filamentous aggregates (12-15 nm in diameter) in the plaque dystrophic
      neurites, and occasionally in neuronal cell bodies. In contrast, phosphorylated
      tau immunoreactivity was observed as clusters distributed along filamentous
      structures accumulating in the dystrophic neurites and around neurotubules in the
      axons. However, no paired helical filaments were observed. Taken together, these
      studies indicate that the PDAPP tg model recapitulates early cytoskeletal
      pathology similar to that observed in AD.

PMID- 11305872
TI  - Recruitment of nonexpanded polyglutamine proteins to intranuclear aggregates in
      neuronal intranuclear hyaline inclusion disease.
AB  - Recruitment of polyglutamine-containing proteins into nuclear inclusions (NIs)
      was investigated in neuronal intranuclear hyaline inclusion disease (NIHID). Some
      polyglutamine-containing proteins, ataxin-2, ataxin-3, and TATA box binding
      protein (TBP), as well as unidentified proteins with expanded polyglutamine
      tracts were recruited into NIs with different frequencies. Ataxin-3 was
      incorporated into most of the NIs and disappeared from its normal cytoplasmic
      localization, whereas only a small fraction of NIs contained ataxin-2 and TBP.
      The consistent presence of ataxin-3 in NIs could reflect a biological feature of
      wild-type ataxin-3, which is translocated into the nucleus under pathological
      conditions and participates in the formation of aggregates. Ataxin-2 also
      accumulated in the nucleus, but was not necessarily incorporated into NIs,
      suggesting that transport of these cytoplasmic proteins into the nucleus and
      their recruitment into NIs are not wholly explained by an interaction with a
      polyglutamine stretch and must be regulated in part by other mechanisms. The
      prevalence of ubiquitin-immunopositive NIs was inversely correlated to neuronal
      loss in all cases examined. This correlation could be explained if NI formation
      is a protective mechanism involving the ubiquitin-proteasome pathway. This
      hypothesis is supported by the finding that the polyglutamine epitope in the
      center of NIs was surrounded by ubiquitin.

PMID- 11305873
TI  - Hippocampal injury and alterations in neuronal chemokine co-receptor expression
      in patients with AIDS.
AB  - Hippocampal neurons express high levels of HIV chemokine co-receptors, activation
      of which causes injury or death in vitro. To determine if their in vivo
      expression correlates with injury, we evaluated neuronal CXCR4 and CCR5
      immunoreactivity and reactive gliosis in autopsy hippocampus of 10 control cases,
      11 AIDS cases without HIV encephalitis (HIVnE) or opportunistic
      infections/lymphomas (OI/L), and 11 AIDS cases with HIV encephalitis (HIVE). All
      groups had higher CXCR4 and CCR5 expression in CA3 and CA4 neurons than CA1
      neurons (p < 0.05). HIVE cases had increased neuronal CXCR4 and decreased
      neuronal CCR5 expression as well as increased numbers of hippocampal GFAP
      positive astrocytes and LN3-positive microglia. Changes were most severe in CA3
      and CA4 and lowest in CA1 regions. These findings also were noted in the 4 HIVE
      cases with neither hippocampal HIVE nor brain OI/L and in the HIVnE groups. This
      study quantitates the regional distribution of hippocampal neuronal CXCR4 and
      CCR5 and shows their respective increase and decrease in AIDS. It suggests a
      relationship between neuronal loss and gliosis with intensity of neuronal
      chemokine expression and raises the possibility of a selective vulnerability of
      hippocampal neurons to AIDS-related injury.

PMID- 11305874
TI  - Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes,
      microglia, and oligodendrocytes grown in culture.
AB  - Erythropoietin (EPO) is a hematopoietic growth factor that stimulates
      proliferation and differentiation of erythroid precursor cells and is also known
      to exert neurotrophic activity in the central nervous system (CNS). However,
      little is known about expression of EPO and EPO receptor (EPOR) in human CNS
      tissues. In the present study, we investigated the effects of proinflammatory
      cytokines on EPO and EPOR expression in highly purified cultures of human
      neurons, astrocytes, microglia, and oligodendrocytes using reverse transcription
      polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).
      EPO mRNA was demonstrated only in human astrocytes, while EPOR expression was
      found in human neurons, astrocytes, and microglia. Neither EPO nor EPOR
      expression was found in oligodendrocytes. In human astrocytes, EPO mRNA and
      secreted EPO protein levels were downregulated after exposure to proinflammatory
      cytokines (IL-1beta, IL-6, or TNF-alpha). In human neurons, TNF-alpha treatment
      markedly increased EPOR expression. These results suggest that proinflammatory
      cytokines regulate expression of EPO and EPOR in human neurons, astrocytes, and
      microglia and further facilitate interactions among different cell types in the
      human CNS.

PMID- 11305875
TI  - Substantia nigra in progressive supranuclear palsy, corticobasal degeneration,
      and parkinsonism-dementia complex of Guam: specific pathological features.
AB  - Disease-specific findings in the substantia nigra were examined in cases of
      progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and
      parkinsonism-dementia complex of Guam (PDC); diseases in which the patients
      exhibit dementia and parkinsonism, with neurofibrillary tangles (NFTs) and glial
      tangles composed of hyperphosphorylated tau. Loss of pigmented neurons was
      extremely severe in these 3 diseases, and decrease of the nonpigmented neurons
      was severe in PSP and CBD. On the other hand, in PDC the decrease of the
      nonpigmented neurons was different in each patient. Topographically, in PSP the
      nonpigmented neurons were particularly depleted in the ventral part and relative
      preservation of the pigmented neurons was observed in the medial part at the
      level examined. Many NFTs were observed in PDC. Although the number of NFTs was
      small, many pretangles were seen in the neurons in CBD. Granular and hazy
      astrocytic inclusions were identified exclusively in PDC. Numerous argyrophilic
      neuropile threads were identified in CBD and PSP, but these were few in PDC. Many
      foamy spheroid bodies as well as coiled bodies were observed in PSP and CBD, but
      only a few were observed in PDC. In conclusion, PDC is a disease that is
      distinctly different from PSP and CBD. It is possible to differentiate between
      PSP and CBD by the occurrence of many pretangles in CBD, but some similarities
      between these 2 diseases indicate the existence of common pathological
      mechanisms.

PMID- 11305876
TI  - The bilateral effect: callosal inhibition or intrahemispheric competition?
AB  - The magnification of visual field asymmetry observed with bilateral compared to
      unilateral tachistoscopic presentation of homologous stimuli (bilateral effect)
      can be explained by two hypothetical processes: homologous activation with
      subsequent inhibition of callosal information transfer or intrahemispheric
      competition for processing resources. A lexical decision task with unilateral and
      bilateral stimulation and response with the right or left hand was used in an
      attempt to decide between these hypotheses. Analysis of response time data
      revealed a bilateral effect, superimposed on a right visual field advantage, and
      no interaction between visual field and response hand. Results are consistent
      with the hypothesis of intrahemispheric competition in the left hemisphere.

PMID- 11305877
TI  - Bimanual coordination in chronic schizophrenia.
AB  - Anomalies of movement are observed both clinically and experimentally in
      schizophrenia. While the basal ganglia have been implicated in its pathogenesis,
      the nature of such involvement is equivocal. The basal ganglia may be involved in
      bimanual coordination through their input to the supplementary motor area (SMA).
      While a neglected area of study in schizophrenia, a bimanual movement task may
      provide a means of assessing the functional integrity of the motor circuit.
      Twelve patients with chronic schizophrenia and 12 matched control participants
      performed a bimanual movement task on a set of vertically mounted cranks at
      different speeds (1 and 2 Hz) and phase relationships. Participants performed in
      phase movements (hands separated by 0 degrees ) and out-of-phase movements (hands
      separated by 180 degrees ) at both speeds with an external cue on or off. All
      participants performed the in-phase movements well, irrespective of speed or
      cueing conditions. Patients with schizophrenia were unable to perform the out-of
      phase movements, particularly at the faster speed, reverting instead to the in
      phase movement. There was no effect of external cueing on any of the movement
      conditions. These results suggest a specific problem of bimanual coordination
      indicative of SMA dysfunction per se and/or faulty callosal integration. A
      disturbance in the ability to switch attention during the out-of-phase task may
      also be involved.

PMID- 11305878
TI  - P300 event-related potential decrements in well-functioning university students
      with mild head injury.
AB  - We compared the performance of 10 well-functioning university students who had
      experienced a mild head injury (MHI) an average of 6.4 years previously and 12
      controls on a series of standard psychometric tests of attention, memory, and
      thinking and on a series of auditory oddball vigilance tasks to which we also
      took event-related potentials (ERPs). The MHI and Control groups performed
      equivalently on all the psychometric tasks and on self-report questionnaires of
      everyday memory and attention difficulties. The MHI group performed more slowly
      and with lower accuracy on only the most difficult of the oddball tasks, yet they
      showed substantially and significantly reduced P300 amplitudes and subsequent
      attentuation on all the oddball tasks, both easy and difficult. There were no
      alterations of N1, P2, and N2 components. These data suggest that despite
      excellent behavioral recovery, subtle information processing deficits involving
      attention nevertheless may persist long after the original injury and may not be
      apparent on a variety of standard psychometric measures.

PMID- 11305879
TI  - An ERP study of famous face incongruity detection in middle age.
AB  - Age-related changes in famous face incongruity detection were examined in middle
      aged (mean = 50.6) and young (mean = 24.8) subjects. Behavioral and ERP responses
      were recorded while subjects, after a presentation of a "prime face" (a famous
      person with the eyes masked), had to decide whether the following "test face" was
      completed with its authentic eyes (congruent) or with other eyes (incongruent).
      The principal effects of advancing age were (1) behavioral difficulties in
      discriminating between incongruent and congruent faces; (2) a reduced N400 effect
      due to N400 enhancement for both congruent and incongruent faces; (3) a latency
      increase of both N400 and P600 components. ERPs to primes (face encoding) were
      not affected by aging. These results are interpreted in terms of early signs of
      aging.

PMID- 11305880
TI  - Preserved implicit learning on both the serial reaction time task and artificial
      grammar in patients with Parkinson's disease.
AB  - Thirteen nondemented patients with Parkinson's disease (PD) were compared with
      age-matched controls on two standard tests of implicit learning. A verbal version
      of the Serial Reaction Time (SRT) task was used to assess sequence learning and
      an artificial grammar (AG) task assessed perceptual learning. It was predicted
      that PD patients would show implicit learning on the AG task but not the SRT
      task, as motor sequence learning is thought to be reliant on the basal ganglia,
      which is damaged in PD. Patients with PD demonstrated implicit learning on both
      tasks. In light of these unexpected results the research on SRT learning in PD is
      reconsidered, and some possible explanations for the sometimes conflicting
      results of PD patient samples on the SRT task are considered. Four factors which
      merit further study in this regard are the degree to which the SRT task relies on
      overt motor responses, the effects of frontal lobe dysfunction upon implicit
      sequence learning, the effects of cerebellar degeneration, and the degree to
      which the illness itself has advanced.

PMID- 11305881
TI  - Stereotypes and steroids: using a psychobiosocial model to understand cognitive
      sex differences.
AB  - To further our understanding of cognitive sex differences, we studied the
      relationship between menstrual phase (via serum estradiol and progesterone
      levels) and cognitive abilities and cognitive performance in a sample of medical
      students in eastern Turkey. As expected, we found no sex differences on the
      Cattell "Culture Fair Intelligence Test" (a figural reasoning test), with females
      scoring significantly higher on a Turkish version of the Finding A's Test (rapid
      word knowledge) and males scoring significantly higher on a paper-and-pencil
      mental rotation test. The women showed a slight enhancement on the Finding A's
      Test and a slight decrement in Cattell scores during the preovulatory phase of
      their cycle that (probably) coincided with a rise in estrogen. There were also
      small cycle-related enhancements in performance for these women on the mental
      rotation test that may reflect cyclical increases in estrogen and progesterone.
      Additional analyses showed an inverted U-shaped function in level of estradiol
      and the Cattell Test. Finally, for women who were tested on Day 10 of their
      menstrual cycle, there was a negative linear relationship between their Cattell
      scores and level of progesterone. Stereotypes about the cognitive abilities of
      males and females did not correspond to performance on the mental rotation or
      Finding A's Test, so the sex-typical results could not be attributed to either
      stereotype threat or stereotype activation. For practical purposes, hormone
      related effects were generally small. Variations over the menstrual cycle do not
      provide evidence for a "smarter" sex, but they do further our understanding of
      steroidal action on human cognitive performance.

PMID- 11305883
TI  - Cognitive and contextual factors in the emergence of diverse belief systems:
      creation versus evolution.
AB  - The emergence and distribution of beliefs about the origins of species is
      investigated in Christian fundamentalist and nonfundamentalist school
      communities, with participants matched by age, educational level, and locale.
      Children (n = 185) and mothers (n = 92) were questioned about animate, inanimate,
      and artifact origins, and children were asked about their interests and natural
      history knowledge. Preadolescents, like their mothers, embraced the dominant
      beliefs of their community, creationist or evolutionist; 8- to 10-year-olds were
      exclusively creationist, regardless of community of origin; 5- to 7-year-olds in
      fundamentalist schools endorsed creationism, whereas nonfundamentalists endorsed
      mixed creationist and spontaneous generationist beliefs. Children's natural
      history knowledge and religious interest predicted their evolutionist and
      creationist beliefs, respectively, independently of parent beliefs. It is argued
      that this divergent developmental pattern is optimally explained with a model of
      constructive interactionism: Children generate intuitive beliefs about origins,
      both natural and intentional, while communities privilege certain beliefs and
      inhibit others, thus engendering diverse belief systems.

PMID- 11305884
TI  - Does learning a complex task have to be complex? A study in learning
      decomposition.
AB  - Many theories of skill acquisition have had considerable success in addressing
      the fine details of learning in relatively simple tasks, but can they scale up to
      complex tasks that are more typical of human learning in the real world? Some
      theories argue for scalability by making the implicit assumption that complex
      tasks consist of many smaller parts, which are learned according to basic
      learning principles. Surprisingly, there has been rather sparse empirical testing
      of this crucial assumption. In this article, we examine this assumption directly
      by decomposing the learning in the Kanfer-Ackerman Air-Traffic Controller Task
      (Ackerman, 1988) from the learning at the global level all the way down to the
      learning at the keystroke level. First, we reanalyze the data from Ackerman
      (1988) and show that the learning in this complex task does indeed reflect the
      learning of smaller parts at the keystroke level. Second, in a follow-up eye
      tracking experiment, we show that a large portion of the learning at the
      keystroke level reflects the learning even at a lower, i.e., attentional level.

PMID- 11305885
TI  - Activation and habituation in olfaction--an fMRI study.
AB  - This study investigated human BOLD responses in primary and higher order
      olfactory cortices following presentation of short- and long-duration odorant
      stimuli using a 3-T MR scanner. The goal was to identify temporal differences in
      the course of the response that might underlie habituation. A short-duration
      stimulus (9 s) consistently activated the primary olfactory cortex (POC). After a
      long stimulus (60 s), the temporal form of the response differed in different
      parts of the olfactory network: (1) The POC (piriform, entorhinal cortex,
      amygdala) and, interestingly, the hippocampus and, to a certain degree, the
      anterior insula show a short, phasic increase in the signal, followed by a
      prolonged decrease below baseline. (2) In the orbitofrontal cortex a sustained
      increase in activation was seen. This increase lasted approximately as long as
      the duration of odorant presentation ( approximately 60 s). (3) The mediodorsal
      nucleus of the thalamus and the caudate nucleus responded with an increase in
      signal which returned to baseline after approximately 15 to 30 s. The correlated
      biphasic hemodynamic response in the POC, hippocampus, and anterior insula during
      prolonged olfactory stimulation suggests that these three areas may interact
      closely with each other in the control of habituation. These results extend
      recent data which showed habituation of the rat piriform cortex and dissociation
      between the POC and the orbitofrontal cortex.

PMID- 11305886
TI  - Estimating tissue deformation between functional images induced by intracranial
      electrode implantation using anatomical MRI.
AB  - This paper examines a solution to the general problem of accurately relating
      points within functional data acquired before and after subdural intracranial
      electrode implantation. We develop an approach based on nonrigid registration of
      high resolution anatomical MRI acquired together with the functional data. This
      makes use of a free-form B-Spline deformation model and registration is recovered
      by maximizing the normalized mutual information between the preimplant MRI and
      the postimplant MRI. We apply the approach to estimate the tissue deformation
      induced by the presence of intracranial electrodes over 15 patient studies.
      Maximum tissue displacements of 4 mm or greater were observed in all cases either
      in the cortex or around the ventricles due to CSF loss. In studies involving
      larger 4 x 4 grids, local tissue displacement estimates exceeded 10 mm from the
      preimplant brain shape. The key issue with this approach is whether the
      deformation estimates are contaminated by the presence of susceptibility-induced
      imaging artifacts. We therefore evaluate the deformation estimates in recovering
      alignment of essentially identical SPECT studies of eight patients acquired
      before and after electrode placement. An ROI-based analysis of the variance of
      resulting subtraction values between pre- and postimplant SPECT was carried out
      in regions of tissue below electrode grids. Results indicate for all cases a
      substantial reduction in residual SPECT subtraction artifacts to a level
      comparable to that in an equivalent region of undeformed tissue.

PMID- 11305887
TI  - Anatomic and functional variability: the effects of filter size in group fMRI
      data analysis.
AB  - In the analysis of group fMRI scans, an optimal spatial filter should be large
      enough to accurately blend functionally homologous anatomic regions, yet small
      enough not to blur the functionally distinct regions. Hanning filters varying
      from 0.0 to 18.0 mm were evaluated in a group analysis of six healthy controls
      performing a simple finger-tapping paradigm. Test-retest reliability and
      Talairach-based measurements of the sensorimotor region were used to explore the
      optimal filter size. Two distinct regions of functional activation were noted in
      the sensorimotor cortex in group images (n = 6) at both time 1 and time 2. These
      regions merge once the filter size exceeds approximately 6.0 mm. The original
      hypothesis that these represented a motor and sensory activation was rejected on
      the basis of structural and functional variability. A discussion of the inherent
      difficulties in choosing an appropriate filter size is presented.

PMID- 11305888
TI  - Reduced event-related current density in the anterior cingulate cortex in
      schizophrenia.
AB  - There is good evidence from neuroanatomic postmortem and functional imaging
      studies that dysfunction of the anterior cingulate cortex plays a prominent role
      in the pathophysiology of schizophrenia. So far, no electrophysiological
      localization study has been performed to investigate this deficit. We
      investigated 18 drug-free schizophrenic patients and 25 normal subjects with an
      auditory choice reaction task and measured event-related activity with 19
      electrodes. Estimation of the current source density distribution in Talairach
      space was performed with low-resolution electromagnetic tomography (LORETA). In
      normals, we could differentiate between an early event-related potential peak of
      the N1 (90-100 ms) and a later N1 peak (120-130 ms). Subsequent current-density
      LORETA analysis in Talairach space showed increased activity in the auditory
      cortex area during the first N1 peak and increased activity in the anterior
      cingulate gyrus during the second N1 peak. No activation difference was observed
      in the auditory cortex between normals and patients with schizophrenia. However,
      schizophrenics showed significantly less anterior cingulate gyrus activation and
      slowed reaction times. Our results confirm previous findings of an electrical
      source in the anterior cingulate and an anterior cingulate dysfunction in
      schizophrenics. Our data also suggest that anterior cingulate function in
      schizophrenics is disturbed at a relatively early time point in the information
      processing stream (100-140 ms poststimulus).

PMID- 11305889
TI  - The functional neural architecture of components of attention in language
      processing tasks.
AB  - Using functional magnetic resonance imaging we examined three important
      dimensions of attentional control (selective attention, divided attention, and
      executive function) in 25 neurologically normal, right-handed men and women,
      using tasks involving the perception and processing of printed words, spoken
      words, or both. In the context of language-processing manipulations: selective
      attention resulted in increased activation at left hemisphere parietal sites as
      well as at inferior frontal sites, divided attention resulted in additional
      increases in activation at these same left hemisphere sites and was also uniquely
      associated with increased activation of homologous sites in the right hemisphere,
      and executive function (measured during a complex task requiring sequential
      decision-making) resulted in increased activation at frontal sites relative to
      all other conditions. Our findings provide support for the belief that specific
      functional aspects of attentional control in language processing involve widely
      distributed but distinctive cortical systems, with mechanisms associated with the
      control of perceptual selectivity involving primarily parietal and inferior
      frontal sites and executive function engaging specific sites in frontal cortex.

PMID- 11305890
TI  - Cortical responses to single mechanoreceptive afferent microstimulation revealed
      with fMRI.
AB  - The technique of intraneural microneurography/microstimulation has been used
      extensively to study contributions of single, physiologically characterized
      mechanoreceptive afferents (MRAs) to properties of somatosensory experience in
      awake human subjects. Its power as a tool for sensory neurophysiology can be
      greatly enhanced, however, by combining it with functional neuroimaging
      techniques that permit simultaneous measurement of the associated CNS responses.
      Here we report its successful adaptation to the environment of a high-field MR
      scanner. Eight median-nerve MRAs were isolated and characterized in three
      subjects and microstimulated in conjunction with fMRI at 3.0 T. Hemodynamic
      responses were observed in every case, and these responses were robust, focal,
      and physiologically orderly. The combination of fMRI with microstimulation will
      enable more detailed studies of the representation of the body surface in human
      somatosensory cortex and further studies of the relationship of that organization
      to short-term plasticity in the human SI cortical response to natural tactile
      stimuli. It can also be used to study many additional topics in sensory
      neurophysiology, such as CNS responses to additional classes of afferents and the
      effects of stimulus patterning and unimodal/crossmodal attentional manipulations.
      Finally, it presents unique opportunities to investigate the basic physiology of
      the BOLD effect and to compare the operating characteristics of fMRI and EEG as
      human functional neuroimaging modalities in an unusually specific and well
      characterized neurophysiological setting.

PMID- 11305891
TI  - Voxel-based morphometry of herpes simplex encephalitis.
AB  - Voxel-based morphometry (VBM) is a powerful tool for analyzing changes in gray or
      white matter density of the brain. By using an automated segmentation procedure
      and standardized parametric statistics it avoids biases inherent in operator
      dependent morphological operations (J. Ashburner and K. J. Friston, 2000,
      NeuroImage 11, 805-821). Since its introduction in 1995, VBM has been used to
      examine anatomical changes in a variety of diseases associated with neurologic
      and psychiatric dysfunction. Given the power of this technique for discerning
      subtle anatomical changes, we wanted to assess its performance on brains with
      gross structural abnormalities. Such results could have implications regarding
      the difficulties to be faced when examining other types of distorted brains
      (e.g., brains with changes due to degenerative disease). This report describes
      the use of VBM for examining individual and group changes in gray matter
      concentration in five patients who had recovered from herpes simplex encephalitis
      (HSE) compared with age- and sex-matched controls. Because HSE tends to affect a
      specific set of brain regions we thought that this would (1) provide an
      opportunity to assess the anatomical face validity of VBM, (2) allow us to assess
      the problems of this technique when used on distorted brains, and (3) provide an
      in vivo demonstration of the gray matter changes due to HSE. We found that,
      despite problems in normalizing and segmenting these severely distorted brains,
      VBM was able to identify correctly a number of the regional gray matter
      abnormalities in HSE. The results, while consistent with the well-known
      histopathology of the disease, also demonstrate potential difficulties with this
      method.

PMID- 11305892
TI  - Occipital activation by pattern recognition in the early blind using auditory
      substitution for vision.
AB  - This PET study aimed at investigating the neural structures involved in pattern
      recognition in early blind subjects using sensory substitution equipment (SSE).
      Six early blind and six blindfolded sighted subjects were studied during three
      auditory processing tasks: a detection task with noise stimuli, a detection task
      with familiar sounds, and a pattern recognition task using the SSE. The results
      showed a differential activation pattern with the SSE as a function of the visual
      experience: in addition to the regions involved in the recognition process in
      sighted control subjects, occipital areas of early blind subjects were also
      activated. The occipital activation was more important when the early blind
      subjects used SSE than during the other auditory tasks. These results suggest
      that activity of the extrastriate visual cortex of early blind subjects can be
      modulated and bring additional evidence that early visual deprivation leads to
      cross-modal cerebral reorganization.

PMID- 11305893
TI  - A cross-linguistic PET study of tone perception in Mandarin Chinese and English
      speakers.
AB  - PET was used in a cross-linguistic study to determine whether neural mechanisms
      subserving pitch perception differ as a function of linguistic relevance. We
      compared tone perception in 12 native Mandarin speakers, who use tonal patterns
      to distinguish lexical meaning, with that of 12 native speakers of a nontone
      language, English. Subjects were scanned under two conditions: a silent resting
      baseline and a tonal task involving discrimination of pitch patterns in Mandarin
      words. Both groups showed common regions of CBF increase, but only Mandarin
      speakers showed additional activation in frontal, parietal, and parieto-occipital
      regions of the left hemisphere; this latter finding indicates that language
      experience may influence brain circuitry in the processing of auditory cues. In
      contrast, only the English group showed activity in the right inferior frontal
      cortex, consistent with a right-hemispheric role in pitch perception.

PMID- 11305894
TI  - Is V1 necessary for conscious vision in areas of relative cortical blindness?
AB  - Visual field defects result from postgeniculate lesions. It is generally assumed
      that absolute defects are caused by total destruction or denervation of primary
      visual cortex (V1) and that the degraded but conscious vision that remains or
      returns in relative or partial defects is mediated by compromised V1 cortex that
      retains a sufficiently large population of functional neurons. We here report the
      results of three patients with long-standing postgeniculate lesions who underwent
      functional magnetic resonance imaging while their partial defect was stimulated
      with high-contrast reversing checkerboard stimuli. Although the stimulation
      evoked conscious visual impressions in all three, in only one patient did it
      activate perilesional V1. In the other two we found no evidence for perilesional
      activation, indicating that some conscious vision may return in the absence of
      functional ipsilesional V1.

PMID- 11305895
TI  - Evidence for a 7- to 9-Hz "sigma" rhythm in the human SII cortex.
AB  - Electrical activity of the human brain features several rhythmical components
      which can be readily studied with whole-scalp neuromagnetometers. We describe a
      new 7- to 9-Hz "sigma" rhythm in the human second somatosensory cortex, distinct
      from both the mu rhythm of the primary sensorimotor cortex and the tau rhythm of
      the supratemporal auditory cortex. Sigma shows rate-selective responsiveness to
      rhythmical median nerve stimulation and is enhanced by stimulation at the
      rhythm's dominant frequency. Single stimuli may trigger several periods of the
      rhythm. The functional significance of the sigma rhythm remains to be
      investigated.

PMID- 11305896
TI  - Probabilistic mapping and volume measurement of human primary auditory cortex.
AB  - Despite their potential utility in clinical and research settings, the range of
      intra- and interindividual variations in size and location of
      cytoarchitectonically defined human primary auditory cortex (PAC) is largely
      unknown. This study demonstrates that gyral patterns and the size and location of
      PAC vary independently to a considerable degree. Thus, the cytoarchitectonic
      borders of PAC cannot be reliably inferred from macroscopic-MR visible-anatomy.
      Given the remarkable topographical variability of architectonic areal borders,
      standard brain mapping which is made solely on the basis of macroanatomic
      landmarks may lead to structural-functional mismatch. Consequently,
      interpretations of individual auditory activity patterns might often be
      inaccurate. In view of the anatomic discrepancies, we generated probability maps
      of PAC in which the degree of intersubject overlap in each stereotaxic position
      was quantified. These maps show that the location of PAC in Talairach space
      differs considerably between hemispheres and individuals. In contrast to earlier
      cytoarchitectonic work which is based in most cases on studies of single brains,
      our systematic approach provides extensive microanatomic data as a reference
      system for studies of human auditory function.

PMID- 11305897
TI  - Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a
      spatial reference system.
AB  - The transverse temporal gyrus of Heschl contains the human auditory cortex.
      Several schematic maps of the cytoarchitectonic correlate of this functional
      entity are available, but they present partly conflicting data (number and
      position of borders of the primary auditory areas) and they do not enable
      reliable comparisons with functional imaging data in a common spatial reference
      system. In order to provide a 3-D data set of the precise position and extent of
      the human primary auditory cortex, its putative subdivisions, and its
      topographical intersubject variability, we performed a quantitative
      cytoarchitectonic analysis of 10 brains using a recently established technique
      for observer-independent definition of areal borders. Three areas, Te1.1, Te1.0,
      and Te1.2, with a well-developed layer IV, which represent the primary auditory
      cortex (Brodmann area 41), can be identified along the mediolateral axis of the
      Heschl gyrus. The cell density was significantly higher in Te1.1 compared to
      Te1.2 in the left but not in the right hemisphere. The cytoarchitectonically
      defined areal borders of the primary auditory cortex do not consistently match
      macroanatomic landmarks like gyral and sulcal borders. The three primary auditory
      areas of each postmortem brain were mapped to a spatial reference system which is
      based on a brain registered by in vivo magnetic resonance imaging. The
      integration of a sample of postmortem brains in a spatial reference system allows
      one to estimate the spatial variability of each cytoarchitectonically defined
      region with respect to this reference system. In future, the transfer of in vivo
      structural and functional data into the same spatial reference system will enable
      accurate comparisons of cytoarchitectonic maps of the primary auditory cortex
      with activation centers as established with functional imaging procedures.

PMID- 11305898
TI  - Early (N70m) neuromagnetic signal topography and striate and extrastriate
      generators following pattern onset quadrant stimulation.
AB  - The MEG signal generated by sinusoidal grating pattern onset at 1 and 3 cpd,
      presented randomly to the four quadrants, was analyzed in terms of gross signal
      properties and current dipole modeling and for a subset of subjects with magnetic
      field tomography (MFT). In all subjects a prominent wave was identified with a
      peak latency around 70 ms (N70m), modulated by spatial frequency and varying
      systematically with the stimulation quadrant. Sensors over occipital areas
      recorded stronger responses with lower field quadrants, while the signal for
      sensors a few centimeters more superior was stronger with upper quadrant stimuli.
      A strong signal in inferior occipitotemporal areas was less sensitive to upper
      and lower field stimulation and was stronger in the left hemisphere with
      contralateral (right) visual field stimulation. For lower visual field
      stimulation a good fit to the average data was obtained with a single dipole for
      3 cpd, but was less consistent across run repetitions for 1 cpd. Neither the
      single-dipole model nor the two-dipole model produced a good fit across runs with
      the upper field stimuli. MFT solutions identified overlapping activity in striate
      and extrastriate areas in all conditions. The MFT solutions in the V1/V2 at the
      N70m were highly reproducible across run repetitions for 1 and 3 cpd, and
      consistent with the cruciform model, even though they were often weaker than
      simultaneously activated extrastriate generators. Extrastriate generators in V5
      and the human homologue of V6, which were variable across run repetitions at
      N70m, settled to highly reproducible activations between 100 and 200 ms.

PMID- 11305899
TI  - Combined analysis of language tasks in fMRI improves assessment of hemispheric
      dominance for language functions in individual subjects.
AB  - Recent advances in functional neuroimaging techniques have prompted an increase
      in the number of studies investigating lateralization of language functions. One
      of the problems in relating findings of various studies to one another is the
      diversity of reported results. This may be due to differences in the tasks that
      are used to stimulate language processing regions and in the control tasks, as
      well as differences in the way imaging data are analyzed,in particular the
      threshold for significance of signal change. We present a simple method to assess
      language lateralization that allows for some variation of tasks and statistical
      thresholding, but at the same time yields reliable and reproducible results.
      Images acquired during a set of word-comprehension and -production tasks are
      analyzed conjointly. As opposed to the use of any one particular task, this
      combined task analysis (CTA) approach is geared toward identifying language
      regions that are involved in generic language functions rather than regions that
      are involved in functions that are specific to a single task. In two experiments
      CTA is compared to single-task analysis in healthy right-handed males. In a third
      experiment left-handed males were examined. Results indicate that CTA: (1)
      improves detection of language-related brain activity in individual subjects and
      (2) yields a high language laterality index (LI) in right-handed males with a
      small variance across subjects. The high LI matches the strong left-hemisphere
      dominance for language that is typical for these subjects as reported in
      neuropsychological and clinical tests in other studies. In the left-handed
      subjects dominance was found either in the left (n = 4) or the right (n = 1)
      hemisphere or was absent (n = 3). The LI derived from CTA is more consistent
      across statistical thresholds for significance of signal change in fMRI analysis
      than in individual-task analysis. Also, the CTA results are very similar to those
      obtained with conjunction analysis of the same data.

PMID- 11305900
TI  - Ranking fMRI time courses by minimum spanning trees: assessing coactivation in
      fMRI.
AB  - In fMRI, time courses with similar temporal "activation" patterns may belong to
      different brain regions (i.e., these regions are functionally connected,
      coactivated). A group of time courses (TCs) corresponding to a particular type of
      temporal activation pattern should be maximally self-consistent (homogeneous). We
      demonstrate that ordering a group of multidimensional fMRI time courses by a
      minimum spanning tree (MST) may be used to investigate the temporal homogeneity
      of a group of TCs. We show the utility of MST ranking for data-driven analysis
      methods in investigating coactivation in fMRI. MST ranking is equally useful for
      hypothesis-led methods. Furthermore, MST ranking enables pairwise comparisons of
      groups/clusters (i.e., any collection of TCs, no matter how derived) of fMRI time
      courses.

PMID- 11305901
TI  - Distinct neural systems for the encoding and recognition of topography and faces.
AB  - In a series of three positron emission tomography experiments the functional
      neuroanatomy of four different types of visual stimuli was investigated within
      the same experimental context. The stimuli were unknown buildings, landscapes,
      human faces, and animal faces. The purpose of the present study was to compare
      the stimulus types, both within the same category and across category, by
      examining if, at encoding (with several seconds exposure to each stimulus) or
      recognition (over time scales of minutes compared to the seconds of usual
      perception/one-back studies), common or different neural circuits were activated
      for all types/categories of stimuli. Within category and although visually very
      different, the encoding of both buildings and landscapes activated a similar set
      of brain regions, including bilateral parahippocampal gyrus. This was in contrast
      to the encoding of both human and animal faces, both of which resulted in
      activation of the fusiform gyrus bilaterally. Despite the perceptual inputs being
      identical to those during encoding, the recognition of both buildings and
      landscapes activated only unilateral right parahippocampal gyrus, while
      recognition of both human and animal faces activated unilateral right fusiform
      gyrus. In addition, right superior frontal gyrus and right inferior and medial
      parietal areas were more active during recognition compared with encoding for all
      stimulus types. Overall the data identify differential patterns of activation for
      encoding compared with retrieval of visual stimuli. Furthermore, medial temporal
      structures specifically are involved in the explicit learning and long-term
      recognition of topographically relevant stimuli, be they buildings or landscapes,
      while lateral temporal structures support nontopographical learning and
      recognition, in this case either human or animal faces.

PMID- 11305902
TI  - Removal of confounding effects of global signal in functional MRI analyses.
AB  - Local signals obtained from BOLD fMRI are generally confounded by global effects.
      In this paper, we make an essential distinction between global effects and the
      global signal. Global effects have a similar influence on local signals from a
      large proportion of cerebral voxels. They may reflect diffuse physiological
      processes or variations in scanner sensitivity and are difficult to measure
      directly. Global effects are often estimated from the global signal, which is the
      spatial average of local signals from all cerebral voxels. If the global signal
      is strongly correlated with experimental manipulations, meaningfully different
      results may be obtained whether or not global effects are modeled (G. K. Aguirre
      et al., 1998, NeuroImage, 8, 302-306). In particular, if local BOLD signals make
      a significant contribution to the global signal, analyses using ANCOVAor
      proportional scaling models may yield artifactual deactivations. In this paper,
      we present a modification to the proportional scaling model that accounts for the
      contribution of local BOLD signals to the global signal. An event-related oddball
      stimulus paradigm and a block design working memory task were used to illustrate
      the efficacy of our model.

PMID- 11305903
TI  - Detection power, estimation efficiency, and predictability in event-related fMRI.
AB  - Experimental designs for event-related functional magnetic resonance imaging can
      be characterized by both their detection power, a measure of the ability to
      detect an activation, and their estimation efficiency, a measure of the ability
      to estimate the shape of the hemodynamic response. Randomized designs offer
      maximum estimation efficiency but poor detection power, while block designs offer
      good detection power at the cost of minimum estimation efficiency. Periodic
      single-trial designs are poor by both criteria. We present here a theoretical
      model of the relation between estimation efficiency and detection power and show
      that the observed trade-off between efficiency and power is fundamental. Using
      the model, we explore the properties of semirandom designs that offer
      intermediate trade-offs between efficiency and power. These designs can
      simultaneously achieve the estimation efficiency of randomized designs and the
      detection power of block designs at the cost of increasing the length of an
      experiment by less than a factor of 2. Experimental designs can also be
      characterized by their predictability, a measure of the ability to circumvent
      confounds such as habituation and anticipation. We examine the relation between
      detection power, estimation efficiency, and predictability and show that small
      increases in predictability can offer significant gains in detection power with
      only a minor decrease in estimation efficiency.

PMID- 11305904
TI  - Enzymes of sphingolipid metabolism: from modular to integrative signaling.
AB  - Many enzymes of sphingolipid metabolism are regulated in response to extra- and
      intracellular stimuli and in turn serve as regulators of levels of bioactive
      lipids (such as sphingosine, ceramide, sphingosine 1-phosphate, and
      diacylglycerol), and as such, they serve a prototypical modular function in cell
      regulation. However, lipid metabolism is also closely interconnected in that a
      product of one enzyme serves as a substrate for another. Moreover, many cell
      stimuli regulate more than one of these enzymes, thus adding to the complexity of
      regulation of lipid metabolism. In this paper, we review the status of enzymes of
      sphingolipid metabolism in cell regulation and propose a role for these enzymes
      in integration of cell responses, a role that builds on the modular organization
      while also taking advantage of the complexity and interconnectedness of lipid
      metabolism, thus providing for a combinatorial mechanism of generating diversity
      in cell responses. This may be a general prototype for the involvement of
      metabolic pathways in cell regulation.

PMID- 11305905
TI  - Calcium regulates S-nitrosylation, denitrosylation, and activity of tissue
      transglutaminase.
AB  - Nitric oxide (NO) and related molecules play important roles in vascular biology.
      NO modifies proteins through nitrosylation of free cysteine residues, and such
      modifications are important in mediating NO's biologic activity. Tissue
      transglutaminase (tTG) is a sulfhydryl rich protein that is expressed by
      endothelial cells and secreted into the extracellular matrix (ECM) where it is
      bound to fibronectin. Tissue TG exhibits a Ca(2+)-dependent transglutaminase
      activity (TGase) that cross-links proteins involved in wound healing, tissue
      remodeling, and ECM stabilization. Since tTG is in proximity to sites of NO
      production, has 18 free cysteine residues, and utilizes a cysteine for catalysis,
      we investigated the factors that regulated NO binding and tTG activity. We report
      that TGase activity is regulated by NO through a unique Ca(2+)-dependent
      mechanism. Tissue TG can be poly-S-nitrosylated by the NO carrier, S
      nitrosocysteine (CysNO). In the absence of Ca(2+), up to eight cysteines were
      nitrosylated without modifying TGase activity. In the presence of Ca(2+), up to
      15 cysteines were found to be nitrosylated and this modification resulted in an
      inhibition of TGase activity. The addition of Ca(2+) to nitrosylated tTG was able
      to trigger the release of NO groups (i.e. denitrosylation). tTG nitrosylated in
      the absence of Ca(2+) was 6-fold more susceptible to inhibition by Mg-GTP. When
      endothelial cells in culture were incubated with tTG and stimulated to produce
      NO, the exogenous tTG was S-nitrosylated. Furthermore, S-nitrosylated tTG
      inhibited platelet aggregation induced by ADP. In conclusion, we provide evidence
      that Ca(2+) regulates the S-nitrosylation and denitrosylation of tTG and thereby
      TGase activity. These data suggest a novel allosteric role for Ca(2+) in
      regulating the inhibition of tTG by NO and a novel function for tTG in dispensing
      NO bioactivity.

PMID- 11305906
TI  - Biophysical characterization of recombinant human Bcl-2 and its interactions with
      an inhibitory ligand, antimycin A.
AB  - Apoptosis is an essential physiological process, regulated by the family of Bcl-2
      related proteins. However, the molecular mechanism by which Bcl-2 regulates
      apoptosis still remains elusive. Here we report the functional studies of
      recombinant human Bcl-2 with the deletion of 22 residues at the C-terminal
      membrane-anchoring region (rhBcl-2Delta22). Characterization of rhBcl-2Delta22
      showed that the recombinant protein is homogeneous and monodisperse in
      nondenaturing solutions, stable at room temperature in the presence of a metal
      chelator, and an alpha-helical protein with unfolding of secondary structure at a
      T(m) of 62.8 degrees C. Optimal membrane pore formation by rhBcl-2Delta22
      required negatively charged phospholipids. The existence of a hydrophobic groove
      in rhBcl-2Delta22 was demonstrated by the fluorescence enhancement of the
      hydrophobic ANS probe with which a pro-apoptotic Bak BH3 peptide competed. The
      respiratory inhibitor antimycin A also bound to the hydrophobic groove of rhBcl
      2Delta22 with a K(d) of 0.82 microM. The optimal binding conformation of
      antimycin A was predicted from molecular docking of antimycin A with the hBcl-2
      model created by homology modeling. Antimycin A selectively induces apoptosis in
      cells overexpressing Bcl-2, suggesting that hydrophobic groove-binding compounds
      may act as selective apoptotic triggers in tumor cells.

PMID- 11305907
TI  - The vnd/NK-2 homeodomain: thermodynamics of reversible unfolding and DNA binding
      for wild-type and with residue replacements H52R and H52R/T56W in helix III.
AB  - The conformational stabilities of the vnd (ventral nervous system defective)/NK-2
      homeodomain [HD(wt); residues 1-80 that encompass the 60-residue homeodomain] and
      those harboring mutations in helix III of the DNA recognition site [HD(H52R) and
      HD(H52R/T56W)] have been investigated by differential scanning calorimetry (DSC)
      and ellipticity changes at 222 nm. Thermal unfolding reactions at pH 7.4 are
      reversible and repeatable in the presence of 50-500 mM NaCl with DeltaC(p) = 0.52
      +/- 0.04 kcal K(-1) mol(-1). A substantial stabilization of HD(wt) is produced by
      50 mM phosphate or by the addition of 100-500 mM NaCl to 50 mM Hepes, pH 7.4,
      buffer (from T(m) = 35.5 degrees C to T(m) 43-51 degrees C; DeltaH(vH) congruent
      with 47 +/- 5 kcal mol(-1)). The order of stability is HD(H52R/T56W) > HD(H52R) >
      HD(wt), irrespective of the anions present. Progress curves for ellipticity
      changes at 222 nm as a function of increasing temperature are fitted well by a
      two-state unfolding model, and the cooperativity of secondary structure changes
      is greater for mutant homeodomains than for HD(wt) and also is increased by
      adding 100 mM NaCl to Hepes buffer. A 33% quench of the intrinsic tryptophanyl
      residue fluorescence of HD(wt) by phosphate binding (K(D)' = 2.6 +/- 0.3 mM
      phosphate) is reversed approximately 60% by DNA binding. Thermodynamic parameters
      for vnd/NK-2 homeodomain proteins binding sequence-specific 18 bp DNA have been
      determined by isothermal titration calorimetry (10-30 degrees C). Values of
      DeltaC(p) are +0.25, -0.17, and -0.10 +/- 0.04 kcal K(-1) mol(-1) for HD(wt),
      HD(H52R), and HD(H52R/T56W) binding duplex DNA, respectively. Interactions of
      homeodomains with DNA are enthalpically controlled at 298 K and pH 7.4 with
      corresponding DeltaH values of -6.6 +/- 0.5, -10.8 +/- 0.1, and -9.0 +/- 0.6 kcal
      mol(-1) and DeltaG' values of -11.0 +/- 0.1, -11.0 +/- 0.1, and -11.3 +/- 0.3
      kcal mol(-1) with a binding stoichiometry of 1.0 +/- 0.1. Thermodynamic
      parameters for DNA binding are not predicted from homeodomain structural changes
      that occur upon complexing to DNA and must reflect also solvent and possibly DNA
      rearrangements.

PMID- 11305908
TI  - Lack of catalytic activity of a murine mRNA cytoplasmic serine
      hydroxymethyltransferase splice variant: evidence against alternative splicing as
      a regulatory mechanism.
AB  - Mammalian serine hydroxymethyltransferase (SHMT) is a tetrameric, pyridoxal
      phosphate-dependent enzyme that catalyzes the reversible interconversion of
      serine and tetrahydrofolate to glycine and methylenetetrahydrofolate. This
      reaction generates single-carbon units for purine, thymidine, and methionine
      biosynthesis. Cytoplasmic SHMT (cSHMT) has been postulated to channel one-carbon
      substituted folates to various folate-dependent enzymes, and alternative splicing
      of the cSHMT transcript may be a mechanism that enables specific protein-protein
      interactions. The cytoplasmic isozyme is expressed from species-specific and
      tissue-specific alternatively spliced transcripts that encode proteins with
      modified carboxy-terminal domains, while the mitochondrial isozyme is expressed
      from a single transcript. While the full-length mouse and human cSHMT proteins
      are 91% identical, their alternatively spliced transcripts differ. The murine
      cSHMT gene is expressed as two transcripts. One transcript encodes a full-length
      55 kDa active enzyme (cSHMT), while the other transcript encodes a 35 kDa protein
      (McSHMTtr). The McSHMTtr protein present in mouse liver and kidney does not bind
      5-formyltetrahydrofolate, nor does it oligomerize with the full-length cSHMT
      enzyme. While recombinant cSHMT-glutathione S-transferase fusion proteins form
      tetramers and are catalytically active, McSHMTtr-glutathione S-transferase fusion
      proteins are catalytically inactive, do not form heterotetramers, and do not bind
      pyridoxal phosphate. Analysis of the murine cSHMT crystal structure indicates
      that the active site lysine that normally binds pyridoxal phosphate in the cSHMT
      protein is exposed to solvent in the McSHMTtr protein, preventing stable
      formation of a Schiff base with pyridoxal phosphate. Modeling studies suggest
      that the human cSHMT proteins expressed from alternatively spliced transcripts
      are inactive as well. Therefore, channeling mechanisms enabling specific protein
      protein interactions of active enzymes are not based on cSHMT alternative
      splicing.

PMID- 11305909
TI  - Equilibrium unfolding of dimeric desulfoferrodoxin involves a monomeric
      intermediate: iron cofactors dissociate after polypeptide unfolding.
AB  - Here we report the conformational stability of homodimeric desulfoferrodoxin
      (dfx) from Desulfovibrio desulfuricans (ATCC 27774). The dimer is formed by two
      dfx monomers linked through beta-strand interactions in two domains; in addition,
      each monomer contains two different iron centers: one Fe-(S-Cys)(4) center and
      one Fe-[S-Cys+(N-His)(4)] center. The dissociation constant for dfx was
      determined to be 1 microM (DeltaG = 34 kJ/mol of dimer) from the concentration
      dependence of aromatic residue emission. Upon addition of the chemical denaturant
      guanidine hydrochloride (GuHCl) to dfx, a reversible fluorescence change occurred
      at 2-3 M GuHCl. This transition was dependent upon protein concentration, in
      accord with a dimer to monomer reaction [DeltaG(H(2)O) = 46 kJ/mol of dimer]. The
      secondary structure did not disappear, according to far-UV circular dichroism
      (CD), until 6 M GuHCl was added; this transition was reversible (for incubation
      times of < 1 h) and independent of dfx concentration [DeltaG(H(2)O) = 50 kJ/mol
      of monomer]. Thus, dfx equilibrium unfolding is at least three-state, involving a
      monomeric intermediate with native-like secondary structure. Only after complete
      polypeptide unfolding (and incubation times of > 1 h) did the iron centers
      dissociate, as monitored by disappearance of ligand-to-metal charge transfer
      absorption, fluorescence of an iron indicator, and reactivity of cysteines to
      Ellman's reagent. Iron dissociation took place over several hours and resulted in
      an irreversibly denatured dfx. It appears as if the presence of the iron centers,
      the amino acid composition, and, to a lesser extent, the dimeric structure are
      factors that aid in facilitating dfx's unusually high thermodynamic stability for
      a mesophilic protein.

PMID- 11305910
TI  - Contribution of the active site histidine residues of ribonuclease A to nucleic
      acid binding.
AB  - His12 and His119 are critical for catalysis of RNA cleavage by ribonuclease A
      (RNase A). Substitution of either residue with an alanine decreases the value of
      k(cat)/K(M) by more than 10(4)-fold. His12 and His119 are proximal to the
      scissile phosphoryl group of an RNA substrate in enzyme-substrate complexes.
      Here, the role of these active site histidines in RNA binding was investigated by
      monitoring the effect of mutagenesis and pH on the stability of enzyme-nucleic
      acid complexes. X-ray diffraction analysis of the H12A and H119A variants at a
      resolution of 1.7 and 1.8 A, respectively, shows that the amino acid
      substitutions do not perturb the overall structure of the variants. Isothermal
      titration calorimetric studies on the complexation of wild-type RNase A and the
      variants with 3'-UMP at pH 6.0 show that His12 and His119 contribute 1.4 and 1.1
      kcal/mol to complex stability, respectively. Determination of the stability of
      the complex of wild-type RNase A and 6-carboxyfluorescein approximately d(AUAA)
      at varying pHs by fluorescence anisotropy shows that the stability increases by
      2.4 kcal/mol as the pH decreases from 8.0 to 4.0. At pH 4.0, replacing His12 with
      an alanine residue decreases the stability of the complex with 6
      carboxyfluorescein approximately d(AUAA) by 2.3 kcal/mol. Together, these
      structural and thermodynamic data provide the first thorough analysis of the
      contribution of histidine residues to nucleic acid binding.

PMID- 11305911
TI  - A structural characterization of the interactions between titin Z-repeats and the
      alpha-actinin C-terminal domain.
AB  - Titin and alpha-actinin, two modular muscle proteins, are with actin the major
      components of the Z-band in vertebrate striated muscles where they serve to
      organize the antiparallel actin filament arrays in adjacent sarcomeres and to
      transmit tension between sarcomeres during activation. Interactions between titin
      and alpha-actinin have been mainly localized in a 45-amino acid multiple motif (Z
      repeat) in the N-terminal region of titin and the C-terminal region of alpha
      actinin. In this study, we provide the first quantitative characterization of
      alpha-actinin-Z-repeat recognition and dissect the interaction to its minimal
      units. Different complementary techniques, such as circular dichroism,
      calorimetry, and nuclear magnetic spectroscopy, were used. Two overlapping alpha
      actinin constructs (Act-EF34 and Act-EF1234) containing two and four EF-hand
      motifs, respectively, were produced, and their folding properties were examined.
      Complex formation of Act-EF34 and Act-EF1234 with single- and double-Z-repeat
      constructs was studied. Act-EF34 was shown quantitatively to be necessary and
      sufficient for binding to Z-repeats, excluding the presence of additional high
      affinity binding sites in the remaining part of the domain. The binding
      affinities of the different Z-repeats for Act-EF34 range from micromolar to
      millimolar values. The strongest of these interactions are comparable to those
      observed in troponin C-troponin I complexes. The binding affinities for Act-EF34
      are maximal for Zr1 and Zr7, the two highly homologous sequences present in all
      muscle isoforms. No cooperative or additional contributions to the interaction
      were observed for Z-repeat double constructs. These findings have direct
      relevance for evaluating current models of Z-disk assembly.

PMID- 11305912
TI  - Rat coagulating gland secretion contains a kinesin heavy chain-like protein
      acting as a type IV transglutaminase substrate.
AB  - By a proteomic approach, we demonstrated in rat coagulating gland secretion the
      presence of a 120 kDa protein which shares at least 80% identity at the amino
      acid level with the most closely related kinesin heavy chain codified by the
      kinesin superfamily protein Kif5c gene. In addition, we identified 30 and 66 kDa
      proteolytic fragments of such a kinesin heavy chain-like protein, corresponding
      to the 73-299 N-terminal and 300-860 C-terminal regions, respectively. Finally,
      we demonstrated the occurrence in coagulating gland secretion of a 200 kDa
      protein probably derived by cross-linking reaction of the kinesin heavy chain
      like protein with type IV transglutaminase. In fact, kinesin heavy chain-like
      protein and its 66 kDa proteolytic fragment were also found to act as effective
      acyl donor substrates for the enzyme in vitro.

PMID- 11305913
TI  - Electrostatic steering and ionic tethering in the formation of thrombin-hirudin
      complexes: the role of the thrombin anion-binding exosite-I.
AB  - Electrostatic interactions between the thrombin anion-binding exosite-I (ABE-I)
      and the hirudin C-terminal tail play an important role in the formation of the
      thrombin-hirudin inhibitor complex and serves as a model for the interactions of
      thrombin with its many other ligands. The role of each solvent exposed basic
      residue in ABE-I (Arg(35), Lys(36), Arg(67), Arg(73), Arg(75), Arg(77a), Lys(81),
      Lys(109), Lys(110), and Lys(149e)) in electrostatic steering and ionic tethering
      in the formation of thrombin-hirudin inhibitor complexes was explored by site
      directed mutagenesis. The contribution to the binding energy (deltaG(degrees)b)
      by each residue varied from 1.9 kJ mol(-)(1) (Lys(110)) to 15.3 kJ mol(-1)
      (Arg(73)) and were in general agreement to their observed interactions with
      hirudin residues in the thrombin-hirudin crystal structure [Rydel, T. J.,
      Tulinsky, A., Bode, W., and Huber, R. (1991) J. Mol. Biol. 221, 583-601].
      Coupling energies (delta deltaG(degrees) int) were calculated for the major ion
      pair interactions involved in ionic tethering using complementary hirudin mutants
      (h-D55N, h-E57Q, and h-E58Q). Cooperativity was seen for the h-Asp(55)/Arg(73)
      ion pair (2.4 kJ mol(-1)); however, low coupling energies for h-Asp(55)/Lys(149e)
      (deltadeltaG(degrees)int 0.6 kJ mol(-1)) and h-Glu(58)/Arg(77a)
      (deltadeltaG(degrees)int 0.9 kJ mol(-1)) suggest these are not major
      interactions, as anticipated by the crystal structure. Interestingly, high
      coupling energies were seen for the intermolecular ion-pair h-Glu(57)/Arg(75)
      (deltadeltaG(degrees)int 2.3 kJ mol(-1)) and for the solvent bridge h
      Glu(57)/Arg(77a) (deltadeltaG(degrees)int 2.7 kJ mol(-1)) indicating that h
      Glu(57) interacts directly with both Arg(75) and Arg(77a) in the thrombin-hirudin
      inhibitor complex. The remaining ABE-I residues that do not form major contacts
      in tethering the C-terminal tail of hirudin make small but collectively important
      contributions to the overall positive electrostatic field generated by ABE-I
      important in electrostatic steering.

PMID- 11305914
TI  - Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex by an
      allosteric mechanism.
AB  - Phosphorothioate oligonucleotides (PS ODNs) prolong the activated partial
      thromboplastin time in human plasma by inhibition of intrinsic tenase (factor IXa
      factor VIIIa) activity. This inhibition was characterized using ISIS 2302, a 20
      mer antisense PS ODN. ISIS 2302 demonstrated hyperbolic, mixed-type inhibition of
      factor X activation by the intrinsic tenase complex. The decrease in V(max(app))
      was analyzed by examining complex assembly, cofactor stability, and protease
      catalysis. ISIS 2302 did not inhibit factor X activation by the factor IXa
      phospholipid complex, or significantly affect factor VIII-phospholipid affinity.
      Inhibitory concentrations of ISIS 2302 modestly decreased the affinity of factor
      IXa-factor VIIIa binding in the presence of phospholipid (K(D) = 11.5 vs 4.8 nM).
      This effect was insufficient to explain the reduction in V(max(app)). ISIS 2302
      did not affect the in vitro half-life of factor VIIIa, suggesting it did not
      destabilize cofactor activity. In the presence of 30% ethylene glycol, the level
      of factor X activation by the factor IXa-phospholipid complex increased 3-fold,
      and the level of chromogenic substrate cleavage by factor IXa increased more than
      50-fold. ISIS 2302 demonstrated partial inhibition of factor X activation by the
      factor IXa-phospholipid complex, and chromogenic substrate cleavage by factor
      IXa, only in the presence of ethylene glycol. Like the intact enzyme complex,
      ISIS 2302 demonstrated hyperbolic, mixed-type inhibition of chromogenic substrate
      cleavage by factor IXa (K(I) = 88 nM). Equilibrium binding studies with
      fluorescein-labeled ISIS 2302 demonstrated a similar affinity (K(D) = 92 nM) for
      the PS ODN-factor IX interaction. These results suggest that PS ODNs bind to an
      exosite on factor IXa, modulating catalytic activity of the intrinsic tenase
      complex.

PMID- 11305915
TI  - Importance of basic residues and quaternary structure in the function of MIP-1
      beta: CCR5 binding and cell surface sugar interactions.
AB  - Chemokines direct immune cells toward sites of infection by establishing a
      gradient across the extracellular matrix of the tissue. This gradient is thought
      to be stabilized by ligation of chemokines to sulfated polysaccharides known as
      glycosaminoglycans (GAGs) that are found on the surface of endothelial and other
      cells as well as in the tissue matrix. GAGs interact with chemokines and in some
      cases cause them to aggregate. The interaction between cell surface GAGs and
      chemokines has also been postulated to play a role in the anti-HIV activity of
      some chemokines, including MIP-1beta. Since many proteins interact with GAGs by
      utilizing basic residues, we mutated R18, K45, R46, and K48 in MIP-1beta to
      investigate the role of these residues in GAG binding and CCR5 function. We find
      that no single amino acid substitution alone has a dramatic effect on heparin
      binding, although change at R46 has a moderate effect. However, binding to
      heparin is completely abrogated in a mutant (K45A/R46A/K48A) in which the entire
      "40's loop" has been neutralized. A functional study of these mutants reveals
      that the charged residues in this 40's loop, particularly K48 and R46, are
      critical mediators of MIP-1beta binding to its receptor CCR5. However, despite
      the partially overlapping function of the residues in the 40's loop in binding to
      both CCR5 and heparin, the presence of cell surface sugars does not appear to be
      necessary for the ability of MIP-1beta to function on its receptor CCR5, as
      enzymatic removal of GAGs from cells results in little effect on MIP-1beta
      activity. Because the means by which the chemokine gradient transmits information
      to the recruited cells is not well defined, we also mutated the basic residues in
      MIP(9), a truncated form of MIP-1beta that is impaired in its ability to
      dimerize, to probe whether the quaternary structure of this chemokine influences
      its ability to bind heparin. None of the truncated variants bound as well as the
      full-length proteins containing the same mutation, suggesting that the MIP-1beta
      dimer participates in heparin binding.

PMID- 11305916
TI  - Sensitivity of single membrane-spanning alpha-helical peptides to hydrophobic
      mismatch with a lipid bilayer: effects on backbone structure, orientation, and
      extent of membrane incorporation.
AB  - The extent of matching of membrane hydrophobic thickness with the hydrophobic
      length of transmembrane protein segments potentially constitutes a major director
      of membrane organization. Therefore, the extent of mismatch that can be
      compensated, and the types of membrane rearrangements that result, can provide
      valuable insight into membrane functionality. In the present study, a large
      family of synthetic peptides and lipids is used to investigate a range of
      mismatch situations. Peptide conformation, orientation, and extent of
      incorporation are assessed by infrared spectroscopy, tryptophan fluorescence,
      circular dichroism, and sucrose gradient centrifugation. It is shown that peptide
      backbone structure is not significantly affected by mismatch, even when the
      extent of mismatch is large. Instead, this study demonstrates that for tryptophan
      flanked peptides the dominant response of a membrane to large mismatch is that
      the extent of incorporation is reduced, when the peptide is both too short and
      too long. With increasing mismatch, a smaller fraction of peptide is incorporated
      into the lipid bilayer, and a larger fraction is present in extramembranous
      aggregates. Relatively long peptides that remain incorporated in the bilayer have
      a small tilt angle with respect to the membrane normal. The observed effects
      depend on the nature of the flanking residues: long tryptophan-flanked peptides
      do not associate well with thin bilayers, while equisized lysine-flanked peptides
      associate completely, thus supporting the notion that tryptophan and lysine
      interact differently with membrane-water interfaces. The different properties
      that aromatic and charged flanking residues impart on transmembrane protein
      segments are discussed in relation to protein incorporation in biological
      systems.

PMID- 11305917
TI  - Folding mechanism of ketosteroid isomerase from Comamonas testosteroni.
AB  - Ketosteroid isomerase (KSI) from Comamonas testosteroni is a homodimeric enzyme
      with 125 amino acids in each monomer catalyzing the allylic isomerization
      reaction at rates comparable to the diffusion limit. Kinetic analysis of KSI
      refolding has been carried out to understand its folding mechanism. The refolding
      process as monitored by fluorescence change revealed that the process consists of
      three steps with a unimolecular fast, a bimolecular intermediate, and most likely
      unimolecular slow phases. The fast refolding step might involve the formation of
      structured monomers with hydrophobic surfaces that seem to have a high binding
      capacity for the amphipathic dye 8-anilino-1-naphthalenesulfonate. During the
      refolding process, KSI also generated a state that can bind equilenin, a reaction
      intermediate analogue, at a very early stage. These observations suggest that the
      KSI folding might be driven by the formation of the apolar active-site cavity
      while exposing hydrophobic surfaces. Since the monomeric folding intermediate may
      contain more than 83% of the native secondary structures as revealed previously,
      it is nativelike taking on most of the properties of the native protein. Urea
      dependence analysis of refolding revealed the existence of folding intermediates
      for both the intermediate and slow steps. These steps were accelerated by
      cyclophilin A, a prolyl isomerase, suggesting the involvement of a cis-trans
      isomerization as a rate-limiting step. Taken together, we suggest that KSI folds
      into a monomeric intermediate, which has nativelike secondary structure, an
      apolar active site, and exposed hydrophobic surface, followed by dimerization and
      prolyl isomerizations to complete the folding.

PMID- 11305919
TI  - Superoxide reductase from Desulfoarculus baarsii: reaction mechanism and role of
      glutamate 47 and lysine 48 in catalysis.
AB  - Superoxide reductase (SOR) is a small metalloenzyme that catalyzes reduction of
      O(2)(*)(-) to H(2)O(2) and thus provides an antioxidant mechanism against
      superoxide radicals. Its active site contains an unusual mononuclear ferrous
      center, which is very efficient during electron transfer to O(2)(*)(-) [Lombard,
      M., Fontecave, M., Touati, D., and Niviere, V. (2000) J. Biol. Chem. 275, 115
      121]. The reaction of the enzyme from Desulfoarculus baarsii with superoxide was
      studied by pulse radiolysis methods. The first step is an extremely fast
      bimolecular reaction of superoxide reductase with superoxide, with a rate
      constant of (1.1 +/- 0.3) x 10(9) M(-1) s(-1). A first intermediate is formed
      which is converted to a second one at a much slower rate constant of 500 +/- 50
      s(-1). Decay of the second intermediate occurs with a rate constant of 25 +/- 5
      s(-1). These intermediates are suggested to be iron-superoxide and iron-peroxide
      species. Furthermore, the role of glutamate 47 and lysine 48, which are the
      closest charged residues to the vacant sixth iron coordination site, has been
      investigated by site-directed mutagenesis. Mutation of glutamate 47 into alanine
      has no effect on the rates of the reaction. On the contrary, mutation of lysine
      48 into an isoleucine led to a 20-30-fold decrease of the rate constant of the
      bimolecular reaction, suggesting that lysine 48 plays an important role during
      guiding and binding of superoxide to the iron center II. In addition, we report
      that expression of the lysine 48 sor mutant gene hardly restored to a superoxide
      dismutase-deficient Escherichia coli mutant the ability to grow under aerobic
      conditions.

PMID- 11305918
TI  - Interaction of apo-cytochrome b5 with cytochromes P4503A4 and P45017A: relevance
      of heme transfer reactions.
AB  - Maximal activity of CYP3A4 is obtained using a reconstitution system consisting
      of NADPH-P450 reductase (CPR), dioleoylphosphatidylcholine (DOPC), an ionic
      detergent, and cytochrome b(5) (b(5)). The mechanism by which b(5) stimulates the
      catalytic activity of CYP3A4 is controversial. Recent data report that apo
      cytochrome b(5) (apo-b(5)) can substitute for holo-b(5) by serving as an
      allosteric effector. These authors concluded that b(5) is not directly involved
      in electron transfer reactions to CYP3A4. We have studied the effect of apo-b(5)
      on the ability of purified CYP3A4 to catalyze the 6beta-hydroxylation of
      testosterone and horse CYP17A to catalyze the 17,20-lyase reaction. The high
      molecular weight form of holo-b(5) (HMW-holo-b(5)) stimulates the 6beta
      hydroxylation of testosterone while the low molecular weight (truncated) form of
      holo-b(5) (LMW-holo-b(5)) does not. When added to the reconstituted system, HMW
      apo-b(5) stimulates the activity of CYP3A4 to a level 50-60% of that obtained
      with HMW-holo-b(5). A similar stimulation of 17alpha-hydroxyprogesterone
      metabolism is seen when studying the CYP17A-catalyzed reaction. Neither LMW-holo
      b(5) nor LMW-apo-b(5) stimulates the activity of CYP3A4 or CYP17A. CYP3A4 forms a
      complex during affinity chromatography with immobilized HMW-holo-b(5) but not
      with immobilized HMW-apo-b(5). Incubation of apo-b(5) with CYP3A4, using
      conditions required for reconstitution of enzymatic activities, results in the
      transfer of heme from the CYP3A4 preparation to apo-b(5), thereby forming holo
      b(5). The separation of heme proteins by thiol-disulfide exchange chromatography
      confirms the formation of holo-b(5). A His67Ala mutant of HMW-b(5) as well as the
      Zn-substituted protoporphyrin derivative of HMW-b(5) do not stimulate the
      activity of either CYP3A4 or CYP17A. These data show that the mechanism of
      stimulation of CYP3A4 and CYP17A activities by apo-b(5) results from the
      formation of holo-b(5) by a heme transfer reaction.

PMID- 11305920
TI  - Reduction precedes cytidylyl transfer without substrate channeling in distinct
      active sites of the bifunctional CDP-ribitol synthase from Haemophilus
      influenzae.
AB  - CDP-ribitol synthase is a bifunctional reductase and cytidylyltransferase that
      catalyzes the transformation of D-ribulose 5-phosphate, NADPH, and CTP to CDP
      ribitol, a repeating unit present in the virulence-associated polysaccharide
      capsules of Haemophilus influenzae types a and b [Follens, A., et al. (1999) J.
      Bacteriol. 181, 2001]. In the work described here, we investigated the order of
      the reactions catalyzed by CDP-ribitol synthase and conducted experiments to
      resolve the question of substrate channeling in this bifunctional enzyme. It was
      determined that the synthase first catalyzed the reduction of D-ribulose 5
      phosphate followed by cytidylyl transfer to D-ribitol 5-phosphate. Steady state
      kinetic measurements revealed a 650-fold kinetic preference for cytidylyl
      transfer to D-ribitol 5-phosphate over D-ribulose 5-phosphate. Rapid mixing
      studies indicated quick reduction of D-ribulose 5-phosphate with a lag in the
      cytidylyl transfer reaction, consistent with a requirement for the accumulation
      of K(m) quantities of D-ribitol 5-phosphate. Signature motifs in the C-terminal
      and N-terminal sequences of the enzyme (short chain dehydrogenase/reductase and
      nucleotidyltransferase motifs, respectively) were targeted with site-directed
      mutagenesis to generate variants that were impaired for only one of the two
      activities (K386A and R18A impaired for reduction and cytidylyl transfer,
      respectively). Release and free diffusion of the metabolic intermediate D-ribitol
      5-phosphate was indicated by the finding that equimolar mixtures of K386A and
      R18A variants were efficient for bifunctional catalysis. Taken together, these
      findings suggest that bifunctional turnover occurs in distinct active sites of
      CDP-ribitol synthase with reduction of D-ribulose 5-phosphate and release and
      free diffusion of the metabolic intermediate D-ribitol 5-phosphate followed by
      cytidylyl transfer.

PMID- 11305921
TI  - Biochemical characterization of the gamma-secretase activity that produces beta
      amyloid peptides.
AB  - Recent studies of gamma-secretase have pointed out that it may be comprised of a
      multisubunit complex with presenilin 1 and presenilin 2 as central components.
      Elucidation of the biochemical mechanism of this enzymatic activity will provide
      important information for developing gamma-secretase inhibitors in Alzheimer's
      disease therapy. Here we describe the biochemical characterization of gamma
      secretase activities using a sensitive, membrane-based assay system. Membranes
      were isolated from 293 cells expressing C99, the substrate of gamma-secretase.
      Upon incubation at 37 degrees C, C99 is cleaved by the endogenous gamma
      secretase, and Abeta peptides are liberated. Abeta40 and Abeta42 gamma-secretase
      activities are very similar in terms of their kinetic profiles and pH dependence,
      supporting the notion that a single enzyme is involved in both Abeta40 and
      Abeta42 production. Pepstatin A inhibited Abeta40 and Abeta42 gamma-secretase
      activities with similar potency. Peptide difluoroketone and peptide aldehyde
      inhibitors inhibited Abeta40 production in a dose-dependent fashion, enhanced
      Abeta42 production at low concentrations, and inhibited Abeta42 production at
      high concentrations. Although the selective increase of Abeta42 by low
      concentrations of peptide difluoroketone and peptide aldehyde inhibitors has been
      reported in intact cells, the finding that this phenomenon occurs in a membrane
      based assay system suggests that these compounds increase Abeta42 by a direct
      effect on gamma-secretase. The ability of these compounds to increase Abeta42
      production may reflect allosteric modulation of the gamma-secretase complex by a
      mechanism related to that responsible for the increase of Abeta42 production by
      mutations in presenilins.

PMID- 11305922
TI  - Quantitation of rate enhancements attained by the binding of cobalamin to
      methionine synthase.
AB  - Cobalamin-dependent methionine synthase (MetH) catalyzes the methylation of
      homocysteine using methyltetrahydrofolate as the methyl donor. The cobalamin
      cofactor serves as an intermediate carrier of the methyl group from
      methyltetrahydrofolate to homocysteine. In the two half-reactions that comprise
      turnover for MetH, the cobalamin is alternatively methylated by
      methyltetrahydrofolate and demethylated by homocysteine to form methionine. Upon
      binding to the protein, the usual dimethylbenzimidazole ligand is replaced by the
      imidazole side chain of His759 [Drennan, C. L., Huang, S., Drummond, J. T.,
      Matthews, R. G., and Ludwig, M. L. (1994) Science 266, 1669-1674]. Despite the
      ligand replacement that accompanies binding of cobalamin to the holo-MetH
      protein, a MetH(2-649) fragment of methionine synthase that contains the regions
      that bind homocysteine and methyltetrahydrofolate utilizes exogenously supplied
      cobalamin in methyl transfer reactions akin to those of the catalytic cycle.
      However, the interactions of MetH(2-649) with endogenous cobalamin are first
      order in cobalamin, while the half-reactions catalyzed by the holoenzyme are zero
      order in cobalamin, so rate constants for reactions of bound and exogenous
      cobalamins cannot be compared. In this paper, we investigate the catalytic rate
      enhancements generated by binding cobalamin to MetH after dividing the protein in
      half and reacting MetH(2-649) with a second fragment, MetH(649-1227), that
      harbors the cobalamin cofactor. The second-order rate constant for demethylation
      of methylcobalamin by Hcy is elevated 60-fold and that for methylation of
      cob(I)alamin is elevated 120-fold. Thus, binding of cobalamin to MetH is
      essential for efficient catalysis.

PMID- 11305923
TI  - Arrangement of apolipoprotein A-I in reconstituted high-density lipoprotein
      disks: an alternative model based on fluorescence resonance energy transfer
      experiments.
AB  - The folding and organization of apolipoprotein A-I (apoA-I) in discoidal, high
      density lipoprotein (HDL) complexes with phospholipids are not yet completely
      resolved. For about 20 years, it was generally accepted that the amphipathic
      helices of apoA-I lie parallel to the acyl chains of the phospholipids ("picket
      fence" model). However, based on the X-ray crystal structure of a large, lipid
      free fragment of apoA-I, a "belt model" was recently proposed. In this model, the
      helices of two antiparallel apoA-I molecules are extended in a circular
      arrangement and lie perpendicular to the phospholipid acyl chains. To obtain
      conclusive information on the spatial organization of apoA-I in discoidal HDL, we
      engineered three separate cysteine mutants of apoA-I (D9C, A124C, A232C) for
      specific labeling with the fluorescence probes ALEXA-488 or ALEXA-546
      (fluorescein and rhodamine derivatives). The labeled apoA-I was reconstituted
      into well-defined HDL complexes containing two molecules of protein and
      dipalmitoylphosphatidylcholine, and the complexes were used in three quantitative
      fluorescence resonance energy transfer (FRET) experiments to determine the
      distances between two specific sites in an HDL particle. Comparison of the
      distances measured by FRET (4.7-7.8 nm) with those predicted from the existing
      models indicated that neither the picket fence nor the belt model can account for
      the experimental results; rather, a hairpin folding of each apoA-I monomer with
      most helices perpendicular to the phospholipid acyl chains and a random head-to
      tail and head-to-head arrangement of the two apoA-I molecules in the HDL
      particles are strongly suggested by the distance and lifetime data.

PMID- 11305924
TI  - Predictability of weak binding from X-ray crystallography: inhaled anesthetics
      and myoglobin.
AB  - Xenon and dichloromethane are inhalational anesthetic agents whose binding to
      myoglobin has been demonstrated by X-ray crystallography. We explore the
      thermodynamic significance of such binding using differential scanning
      calorimetry, circular dichroism spectroscopy, and hydrogen-tritium exchange
      measurements to study the effect of these agents on myoglobin folding stability.
      Though specific binding of these anesthetics might be expected to stabilize
      myoglobin against unfolding, dichloromethane actually destabilized myoglobin at
      all examined concentrations of this anesthetic (15, 40, and 200 mM). On the other
      hand, xenon (1 atm) stabilized myoglobin. Thus, dichloromethane and xenon have
      opposite effects on myoglobin stability despite localization in comparably folded
      X-ray crystallographic structures. These results suggest a need for solution
      measurements to complement crystallography if the consequences of weak binding to
      proteins are to be appreciated.

PMID- 11305925
TI  - Configurations of the N-terminal amphipathic domain of the membrane-bound M13
      major coat protein.
AB  - The M13 major coat protein has been extensively studied in detergent-based and
      phospholipid model systems to elucidate its structure. This resulted in an L
      shaped model structure of the protein in membranes. An amphipathic alpha-helical
      N-terminal arm, which is parallel to the surface of the membrane, is connected
      via a flexible linker to an alpha-helical transmembrane domain. In the present
      study, a fluorescence polarity probe or ESR spin probe is attached to the SH
      group of a series of N-terminal single cysteine mutants, which were reconstituted
      into DOPC model membranes. With ESR spectroscopy, we measured the local mobility
      of N-terminal positions of the protein in the membrane. This is supplemented with
      relative depth measurements at these positions by fluorescence spectroscopy via
      the wavelength of maximum emission and fluorescence quenching. Results show the
      existence of at least two possible configurations of the M13 amphipathic N
      terminal arm on the ESR time scale. The arm is bound either to the membrane
      surface or in the water phase. The removal or addition of a hydrophobic membrane
      anchor by site-specific mutagenesis changes the ratio between the membrane-bound
      and the water phase fraction.

PMID- 11305926
TI  - A fluorescent sensor of the phosphorylation state of nucleoside diphosphate
      kinase and its use to monitor nucleoside diphosphate concentrations in real time.
AB  - A sensor for purine nucleoside diphosphates in solution based on nucleoside
      diphosphate kinase (NDPK) has been developed. A single cysteine was introduced
      into the protein and labeled with the environmentally sensitive fluorophore, N-[2
      (iodoacetamido)ethyl]-7-diethylaminocoumarin-3-carboxamide. The resultant
      molecule shows a 4-fold fluorescence increase when phosphorylated on His117; this
      phosphorylation is on the normal reaction pathway of the enzyme. The emission
      maximum of the phosphoenzyme is at 475 nm, with maximum excitation at 430 nm. The
      fluorescent phosphorylated NDPK is used to measure the amount of ADP and the
      unphosphorylated to measure ATP. The labeled protein is phosphorylated to > 90%,
      and the resultant molecule is stable on ice or can be stored at -80 degrees C.
      The fluorescence responds to the fraction of protein phosphorylated and so to the
      equilibrium between ADP plus NDPK approximately P and ATP plus NDPK. In effect,
      the sensor measures the ADP/ATP concentration ratio. The enzyme has a broad
      specificity for the purine of the nucleotides, so the sensor also can measure
      GDP/GTP ratios. The fluorescence and kinetic properties of the labeled protein
      are described. The binding rate constants of nucleotides are approximately 10(5)
      M(-1) s(-1), and the fluorescence change is at >200 s(-1) when the ADP
      concentration is >1 mM. Results are presented with two well-defined systems,
      namely, the kinetics of ADP release from myosin subfragment 1 and GDP release
      from the small G protein, human rho. The results obtained with this novel sensor
      agree with those from alternate methods and demonstrate the applicability for
      following micromolar changes in nucleoside diphosphate in real time.

PMID- 11305927
TI  - Second-site revertants of a low-sodium-affinity mutant of the Na+/H+ exchanger
      reveal the participation of TM4 into a highly constrained sodium-binding site.
AB  - On the basis of intracellular acidifications in the presence of 30 microM
      cariporide, we selected a fibroblast cell line termed CR5, expressing a mutated
      Na(+)/H(+) exchanger NHE-1 with a low affinity for cariporide (87 +/- 11.6
      microM) and extracellular sodium (248 +/- 63.7 mM). This mutated exchanger
      displays a Phe162Ser substitution in its fourth transmembrane segment. Using
      intracellular acidifications in the presence of 3 mM external sodium on the CR5
      fibroblasts, we isolated two revertants which exhibited a complete recovery for
      sodium affinity but were still resistant to cariporide. Sequencing the cDNAs
      encoding these revertants revealed the presence of two mutations situated at a
      distant location from Phe162 in the same fourth transmembrane segment (Ile169Ser
      and Ile170Thr). Interestingly, introducing these two mutations in the wild-type
      cDNA did not result in a significant increase in affinity for sodium.
      Furthermore, all the mutants characterized in this study display an unchanged
      affinity for lithium, another transported cation. These data suggest that the
      mutation resulting in the low sodium affinity and the two mutations responsible
      for the reversion of this phenotype affect the binding of sodium itself instead
      of the conformational changes triggering substrate translocation. Taken together,
      these results allow us to propose that optimal sodium binding by the Na(+)/H(+)
      exchangers requires the geometrical integrity of a highly constrained sodium
      coordination site.

PMID- 11305928
TI  - Mechanism of action of Escherichia coli ribonuclease III. Stringent chemical
      requirement for the glutamic acid 117 side chain and Mn2+ rescue of the Glu117Asp
      mutant.
AB  - Escherichia coli ribonuclease III (EC 3.1.24) is a double-strand- (ds-) specific
      endoribonuclease involved in the maturation and decay of cellular, phage, and
      plasmid RNAs. RNase III is a homodimer and requires Mg(2+) to hydrolyze
      phosphodiesters. The RNase III polypeptide contains an N-terminal catalytic
      (nuclease) domain which exhibits eight highly conserved acidic residues, at least
      one of which (Glu117) is important for phosphodiester hydrolysis but not for
      substrate binding [Li and Nicholson (1996) EMBO J. 15, 1421-1433]. To determine
      the side chain requirements for activity, Glu117 was changed to glutamine or
      aspartic acid. The mutant proteins were purified as (His)(6)-tagged species, and
      both exhibited normal homodimeric behavior as shown by chemical cross-linking.
      The Glu117Gln mutant is unable to cleave substrate in vitro under all tested
      conditions but can bind substrate. The Glu117Asp mutant also is defective in
      cleavage while able to bind substrate. However, low level activity is observed at
      extended reaction times and high enzyme concentrations, with an estimated
      catalytic efficiency approximately 15 000-fold lower than that of RNase III. The
      activity of the Glu117Asp mutant but not that of the Glu117Gln mutant can be
      greatly enhanced by substituting Mn(2+) for Mg(2+), with the catalytic efficiency
      of the Glu117Asp-Mn(2+) holoenzyme approximately 400-fold lower than that of the
      RNase III-Mn(2+) holoenzyme. For RNase III, a Mn(2+) concentration of 1 mM
      provides optimal activity, while concentrations >5 mM are inhibitory. In
      contrast, the Glu117Asp mutant is not inhibited by high concentrations of Mn(2+).
      Finally, high concentrations of Mg(2+) do not inhibit RNase III nor relieve the
      Mn(2+)-dependent inhibition. In summary, these experiments establish the
      stringent functional requirement for a precisely positioned carboxylic acid group
      at position 117 and reveal two classes of divalent metal ion binding sites on
      RNase III. One site binds either Mg(2+) or Mn(2+) and supports catalysis, while
      the other site is specific for Mn(2+) and confers inhibition. Glu117 is important
      for the function of both sites. The implications of these findings on the RNase
      III catalytic mechanism are discussed.

PMID- 11305929
TI  - Developmental expression of survivin during embryonic submandibular salivary
      gland development.
AB  - BACKGROUND: The regulation of programmed cell death is critical to developmental
      homeostasis and normal morphogenesis of embryonic tissues. Survivin, a member of
      the inhibitors of apoptosis protein (IAP) family primarily expressed in embryonic
      cells, is both an anti-apoptosis and a pro-survival factor. Since our previous
      studies have demonstrated the importance of apoptosis during embryonic
      submandibular salivary gland (SMG) development, we postulated that survivin is a
      likely mediator of SMG epithelial cell survival. RESULTS: We investigated the
      developmental expression of survivin in Pseudoglandular (approximately E14),
      Canalicular (approximately E15) and Terminal Bud (approximately E17) Stage SMGs.
      We report a significant 26% increase in transcript levels between the Canalicular
      and Terminal Bud Stages. Immunohistochemical studies demonstrate nuclear
      localized survivin protein in epithelial cells bounding forming lumina in
      Canalicular and Terminal Bud Stage SMGs. CONCLUSIONS: Survivin is known to be a
      pro-survival and anti-apoptotic factor. Given that survivin translocation into
      the nucleus is required for the induction of entry into the cell cycle and the
      inhibition of apoptosis, our demonstration of nuclear-localized survivin protein
      in presumptive ductal and proacinar lumen-bounding cells suggests that survivin
      may be a key mediator of embryonic SMG epithelial cell survival.

PMID- 11305931
TI  - The slide rule and the calculator.

PMID- 11305930
TI  - Sex differences in risk factors for coronary heart disease: a study in a
      Brazilian population.
AB  - BACKGROUND: In Brazil coronary heart disease (CHD) constitutes the most important
      cause of death in both sexes in all the regions of the country and interestingly,
      the difference between the sexes in the CHD mortality rates is one of the
      smallest in the world because of high rates among women. Since a question has
      been raised about whether or how the incidence of several CHD risk factors
      differs between the sexes in Brazil the prevalence of various risk factors for
      CHD such as high blood cholesterol, diabetes mellitus, hypertension, obesity,
      sedentary lifestyle and cigarette smoking was compared between the sexes in a
      Brazilian population; also the relationships between blood cholesterol and the
      other risk factors were evaluated. RESULTS: The population presented high
      frequencies of all the risk factors evaluated. High blood cholesterol (CHOL) and
      hypertension were more prevalent among women as compared to men. Hypertension,
      diabetes and smoking showed equal or higher prevalence in women in pre-menopausal
      ages as compared to men. Obesity and physical inactivity were equally prevalent
      in both sexes respectively in the postmenopausal age group and at all ages. CHOL
      was associated with BMI, sex, age, hypertension and physical inactivity.
      CONCLUSIONS: In this population the high prevalence of the CHD risk factors
      indicated that there is an urgent need for its control; the higher or equal
      prevalences of several risk factors in women could in part explain the high rates
      of mortality from CHD in females as compared to males.

PMID- 11305932
TI  - An apology for orthologs - or brave new memes.

PMID- 11305933
TI  - Goodbye to 'one by one' genetics.
AB  - The completion of the Arabidopsis thaliana (mustard weed) genome sequence
      constitutes a major breakthrough in plant biology. It will revolutionize how we
      answer questions about the biology and evolution of plants as well as how we
      confront and resolve world-wide agricultural problems.

PMID- 11305934
TI  - The Adaptive Evolution Database (TAED).
AB  - BACKGROUND: Developing an understanding of the molecular basis for the divergence
      of species lies at the heart of biology. The Adaptive Evolution Database (TAED)
      serves as a starting point to link events that occur at the same time in the
      evolutionary history (tree of life) of species, based upon coding sequence
      evolution analyzed with the Master Catalog. The Master Catalog is a collection of
      evolutionary models, including multiple sequence alignments, phylogenetic trees,
      and reconstructed ancestral sequences, for all independently evolving protein
      sequence modules encoded by genes in GenBank [1]. RESULTS: We have estimated from
      these models the ratio of nonsynonymous to synonymous nucleotide substitution
      (Ka/Ks), for each branch in their respective evolutionary trees of every subtree
      containing only chordata or only embryophyta proteins. Branches with high Ka/Ks
      values represent candidate episodes in the history of the family where the
      protein may have undergone positive selection, a phenomenon in molecular
      evolution where the mutant form of a gene must have conferred more fitness than
      the ancestral form. Such episodes are frequently associated with change in
      function. We have found that an unexpectedly large number of families (between 10
      and 20% of those families examined) have at least one branch with a notably high
      Ka/Ks value (putative adaptive evolution). As a resource for biologists wishing
      to understand the interaction between protein sequences and the Darwinian
      processes that shape these sequences, we have collected these into The Adaptive
      Evolution Database (TAED). CONCLUSIONS: Placed in a phylogenetic perspective,
      candidate genes that are undergoing evolution at the same time in the same
      lineage can be viewed together. This framework based upon coding sequence
      evolution can be readily expanded to include other types of evolution. In its
      present form, TAED provides a resource for bioinformaticists interested in data
      mining and for experimental evolutionists seeking candidate examples of adaptive
      evolution for further experimental study.

PMID- 11305935
TI  - Transcription of the genome: don't read it all at once.

PMID- 11305936
TI  - The accelerating convergence of genomics and microbiology.

PMID- 11305937
TI  - Signaling in development.

PMID- 11305938
TI  - A simple model based on mutation and selection explains trends in codon and amino
      acid usage and GC composition within and across genomes.
AB  - BACKGROUND: Correlations between genome composition (in terms of GC content) and
      usage of particular codons and amino acids have been widely reported, but poorly
      explained. We show here that a simple model of processes acting at the nucleotide
      level explains codon usage across a large sample of species (311 bacteria, 28
      archaea and 257 eukaryotes). The model quantitatively predicts responses (slope
      and intercept of the regression line on genome GC content) of individual codons
      and amino acids to genome composition. RESULTS: Codons respond to genome
      composition on the basis of their GC content relative to their synonyms
      (explaining 71-87% of the variance in response among the different codons,
      depending on measure). Amino-acid responses are determined by the mean GC content
      of their codons (explaining 71-79% of the variance). Similar trends hold for
      genes within a genome. Position-dependent selection for error minimization
      explains why individual bases respond differently to directional mutation
      pressure. CONCLUSIONS: Our model suggests that GC content drives codon usage
      (rather than the converse). It unifies a large body of empirical evidence
      concerning relationships between GC content and amino-acid or codon usage in
      disparate systems. The relationship between GC content and codon and amino-acid
      usage is ahistorical; it is replicated independently in the three domains of
      living organisms, reinforcing the idea that genes and genomes at
      mutation/selection equilibrium reproduce a unique relationship between nucleic
      acid and protein composition. Thus, the model may be useful in predicting amino
      acid or nucleotide sequences in poorly characterized taxa.

PMID- 11305939
TI  - A novel sodium bicarbonate cotransporter-like gene in an ancient duplicated
      region: SLC4A9 at 5q31.
AB  - BACKGROUND: Sodium bicarbonate cotransporter (NBC) genes encode proteins that
      execute coupled Na+ and HCO3- transport across epithelial cell membranes. We
      report the discovery, characterization, and genomic context of a novel human NBC
      like gene, SLC4A9, on chromosome 5q31. RESULTS: SLC4A9 was initially discovered
      by genomic sequence annotation and further characterized by sequencing of long
      insert cDNA library clones. The predicted protein of 990 amino acids has 12
      transmembrane domains and high sequence similarity to other NBCs. The 23-exon
      gene has 14 known mRNA isoforms. In three regions, mRNA sequence variation is
      generated by the inclusion or exclusion of portions of an exon. Noncoding SLC4A9
      cDNAs were recovered multiple times from different libraries. The 3' untranslated
      region is fragmented into six alternatively spliced exons and contains expressed
      Alu, LINE and MER repeats. SLC4A9 has two alternative stop codons and six
      polyadenylation sites. Its expression is largely restricted to the kidney. In
      silico approaches were used to characterize two additional novel SLC4A genes and
      to place SLC4A9 within the context of multiple paralogous gene clusters
      containing members of the epidermal growth factor (EGF), ankyrin (ANK) and
      fibroblast growth factor (FGF) families. Seven human EGF-SLC4A-ANK-FGF clusters
      were found. CONCLUSION: The novel sodium bicarbonate cotransporter-like gene
      SLC4A9 demonstrates abundant alternative mRNA processing. It belongs to a growing
      class of functionally diverse genes characterized by inefficient highly variable
      splicing. The evolutionary history of the EGF-SLC4A-ANK-FGF gene clusters
      involves multiple rounds of duplication, apparently followed by large insertions
      and deletions at paralogous loci and genome-wide gene shuffling.

PMID- 11305940
TI  - A basis for a visual language for describing, archiving and analyzing functional
      models of complex biological systems.
AB  - BACKGROUND: We propose that a computerized, internet-based graphical description
      language for systems biology will be essential for describing, archiving and
      analyzing complex problems of biological function in health and disease. RESULTS:
      We outline here a conceptual basis for designing such a language and describe
      BioD, a prototype language that we have used to explore the utility and
      feasibility of this approach to functional biology. Using example models, we
      demonstrate that a rather limited lexicon of icons and arrows suffices to
      describe complex cell-biological systems as discrete models that can be posted
      and linked on the internet. CONCLUSIONS: Given available computer and internet
      technology, BioD may be implemented as an extensible, multidisciplinary language
      that can be used to archive functional systems knowledge and be extended to
      support both qualitative and quantitative functional analysis.

PMID- 11305942
TI  - Development of a 950-gene DNA array for examining gene expression patterns in
      mouse testis.
AB  - BACKGROUND: Over the past five years, interest in and use of DNA array technology
      has increased dramatically, and there has been a surge in demand for different
      types of arrays. Although manufacturers offer a number of pre-made arrays, these
      are generally of utilitarian design and often cannot accommodate the specific
      requirements of focused research, such as a particular set of genes from a
      particular tissue. We found that suppliers did not provide an array to suit our
      particular interest in testicular toxicology, and therefore elected to design and
      produce our own. RESULTS: We describe the procedures used by members of the US
      Environmental Protection Agency MicroArray Consortium (EPAMAC) to produce a mouse
      testis expression array on both filter and glass-slide formats. The approaches
      used in the selection and assembly of a pertinent, nonredundant list of testis
      expressed genes are detailed. Hybridization of the filter arrays with normal and
      bromochloroacetic acid-treated mouse testicular RNAs demonstrated that all the
      selected genes on the array were expressed in mouse testes. CONCLUSION: We have
      assembled two lists of mouse (950) and human (960) genes expressed in the mouse
      and/or human adult testis, essentially all of which are available as sequence
      verified clones from public sources. Of these, 764 are homologous and will
      therefore enable close comparison of gene expression between murine models and
      human clinical testicular samples.

PMID- 11305941
TI  - Conservation of the binding site for the arginine repressor in all bacterial
      lineages.
AB  - BACKGROUND: The arginine repressor ArgR/AhrC is a transcription factor
      universally conserved in bacterial genomes. Its recognition signal (the ARG box),
      a weak palindrome, is also conserved between genomes, despite a very low degree
      of similarity between individual sites within a genome. Thus, the arginine
      repressor is different from two other universal transcription factors - HrcA,
      whose recognition signal is very strongly conserved both within and between
      genomes, and LexA/DinR, whose signal is strongly conserved within, but not
      between, genomes. The arginine regulon is well studied in Escherichia coli and to
      some extent in Bacillus subtilis and some other genomes. Here, we apply the
      comparative genomic approach to the prediction of the ArgR-binding sites in all
      completely sequenced bacterial genomes. RESULTS: Orthologs of ArgR/AhrC were
      identified in the complete genomes of E. coli, Haemophilus influenzae, Vibrio
      choleras, B. subtilis, Mycobacterium tuberculosis, Thermotoga maritima, Chlamydia
      pneumoniae and Deinococcus radiodurans. Candidate arginine repressor binding
      sites were identified upstream of arginine transport and metabolism genes.
      CONCLUSIONS: We found that the ArgR/AhrC recognition signal is conserved in all
      genomes that contain genes encoding orthologous transcription factors of this
      family. All genomes studied except M. tuberculosis contain ABC transport
      cassettes (related to the Art system of E. coli) belonging to the candidate
      arginine regulons.

PMID- 11305944
TI  - Ancient flowering plants: DNA sequences and angiosperm classification.
AB  - Phylogenetic analyses of gene sequences provide a clear pattern of which extant
      flowering plant genera diversified earliest. Combined with complete genomic
      sequences, these data will vastly improve understanding of the genetic basis of
      plant diversity.

PMID- 11305943
TI  - A tale of histone modifications.
AB  - The modification of chromatin structure is important for a number of nuclear
      functions, exemplified by the regulation of transcription. This review discusses
      recent studies of covalent histone modifications and the enzymatic machines that
      generate them.

PMID- 11305945
TI  - Genome-wide analysis of protein-DNA interactions in living cells.
AB  - Understanding the regulation of gene expression requires an analysis of gene
      specific transcription factors. This review highlights recent work that uses
      protein-DNA crosslinking, immunoprecipitation and DNA microarrays to determine
      the binding sites for specific transcription factors throughout the yeast genome.

PMID- 11305946
TI  - Dystrophins and dystrobrevins.
AB  - SUMMARY: A unique arrangement of domains makes up the common region of two
      otherwise very different proteins - long, elegant dystrophin, and its rather
      dumpy distant cousin, dystrobrevin. The two work in concert, forming the core of
      a large membrane-bound complex in all metazoa. Like many proteins, dystrophin and
      dystrobrevin have diversified in the vertebrate clade, as have their binding
      partners, yielding specialized complexes tailored to different cellular and
      subcellular locations. Disruption of several components of the complex is known
      to result in syndromes that include progressive myopathy, sometimes combined with
      cognitive defects; the best known of these is Duchenne muscular dystrophy.
      Despite a wealth of biochemical, cell biological and genetic information, the
      precise role of dystrophins, dystrobrevins and their collaborators remains
      unclear.

PMID- 11305947
TI  - The complexities of breast cancer desmoplasia.
AB  - The stromal, or 'desmoplastic', responses seen histologically in primary breast
      carcinomas can vary from being predominantly cellular
      (fibroblasts/myofibroblasts) with little collagen to being a dense acellular
      tissue. The mechanisms underlying the stromal response are complex; paracrine
      activation of myofibroblasts by growth factors is important but the contribution
      of cytokines/chemokines should not be ignored. A recent xenograft study has
      proposed that platelet-derived growth factor (PDGF) is the initiator of the
      desmoplastic response, but this has not been confirmed by (limited) analyses in
      vivo. Further studies are required to elaborate the mechanisms of the
      desmoplastic response, to determine its role in breast cancer progression and
      whether it is the same for all carcinomas.

PMID- 11305948
TI  - Telomerase and breast cancer.
AB  - Current therapies for breast cancer include treatments that are toxic and often
      result in drug resistance. Telomerase, a cellular reverse transcriptase that
      maintains the ends of chromosomes (telomeres), is activated in the vast majority
      of breast cancers (over 90% of breast carcinomas) but not in normal adjacent
      tissues. Telomerase is thus an attractive target for both diagnosis and therapy
      because of its distinct pattern of expression. We address the use of telomerase
      in the diagnostics of breast pathology, as well as the use of telomerase
      inhibitors in the treatment and prevention of breast cancer.

PMID- 11305949
TI  - Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?
AB  - Drug resistance is a fundamental problem in the treatment of most common human
      cancers. Our understanding of the cellular mechanisms underlying death and
      survival has allowed the development of rational approaches to overcoming drug
      resistance. The mitogen activated protein kinase family of protein
      serine/threonine kinases has been implicated in this complex web of signalling,
      with some members acting to enhance death and other members to prevent it. A
      recent publication by MacKeigan et al is the first to demonstrate an enhancement
      of drug-induced cell death by simultaneous blockade of MEK-mediated survival
      signalling, and offers the potential for targeted adjuvant therapy as a means of
      overcoming drug resistance.

PMID- 11305950
TI  - More breast cancer genes?
AB  - A new gene associated with a high risk of breast cancer, termed BRCAX, may exist
      on chromosome 13q. Tumours from multicase Nordic breast cancer families, in which
      mutations in BRCA1 and BRCA2 had been excluded, were analyzed using comparative
      genomic hybridization in order to identify a region of interest, which was
      apparently confirmed and refined using linkage analysis on an independent sample.
      The present commentary discusses this work. It also asks why there should exist
      genetic variants associated with susceptibility to breast cancer other than
      mutations in BRCA1 and BRCA2, and what might be their modes of inheritance,
      allele frequencies and risks. Replication studies will be needed to clarify
      whether there really is a tumour suppressor gene other than BRCA2 on chromosome
      13q.

PMID- 11305952
TI  - Update on endocrine aspects of breast cancer: report from the 23rd San Antonio
      Breast Cancer Symposium, San Antonio, Texas, USA, 6-9 December 2000.

PMID- 11305951
TI  - Applications of microarray technology in breast cancer research.
AB  - Microarrays provide a versatile platform for utilizing information from the Human
      Genome Project to benefit human health. This article reviews the ways in which
      microarray technology may be used in breast cancer research. Its diverse
      applications include monitoring chromosome gains and losses, tumour
      classification, drug discovery and development, DNA resequencing, mutation
      detection and investigating the mechanism of tumour development.

PMID- 11305953
TI  - Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary
      node invasion at the time of rescue mastectomy after induction chemotherapy.
AB  - BACKGROUND: Axillary node status after induction chemotherapy for locally
      advanced breast cancer has been shown on multivariate analysis to be an
      independent predictor of relapse. However, it has been postulated that responders
      to induction chemotherapy with a clinically negative axilla could be spared the
      burden of lymphadenectomy, because most of them will not show histological nodal
      invasion. P-glycoprotein expression in the rescue mastectomy specimen has finally
      been identified as a significant predictor of patient survival. MATERIALS AND
      METHODS: We studied the expression of the genes encoding multidrug resistance
      associated protein (MDR1) and lung cancer associated resistance protein (LRP) in
      formalin-fixed, paraffin-embedded tumor samples from 52 patients treated for
      locally advanced breast cancer by means of induction chemotherapy followed by
      rescue mastectomy. P-glycoprotein expression was assessed by means of
      immunohistochemistry before treatment in 23 cases, and by means of reverse
      transcriptase-mediated polymerase chain reaction (RT-PCR) after treatment in 46
      (6 failed). LRP expression was detected by means of immunohistochemistry, with
      the LRP-56 monoclonal antibody, in 31 cases before treatment.
      Immunohistochemistry for detecting the expression of c-erb-B2, p53, Ki67,
      estrogen receptor and progesterone receptor are routinely performed in our
      laboratory in every case, and the results obtained were included in the study.
      All patients had received between two and six cycles of standard 5-fluorouracil,
      doxorubicin and cyclophosphamide (FAC) chemotherapy, with two exceptions [one
      patient received four cycles of a docetaxel-adriamycin combination, and the other
      four cycles of standard cyclophosphamide-methotrexate-5-fluorouracil (CMF)
      polychemotherapy]. Response was assessed in accordance with the Response
      Evaluation Criteria In Solid Tumors (RECIST). By these, 2 patients achieved a
      complete clinical response, 37 a partial response, and the remaining 13 showed
      stable disease. This makes a total clinical response rate of 75.0%. None achieved
      a complete pathological response. RESULTS: MDR1 mRNA expression detected by RT
      PCR was associated with the presence of invaded axillary nodes at surgery in
      18/22 cases (81.8%), compared with 13/24 (54.2%) in the group with undetectable
      MDR1 expression. This difference was statistically significant (P < 0.05). LRP
      expression in more than 20% of tumor cells before any treatment was associated
      with axillary nodal metastasis after chemotherapy and rescue mastectomy in 17/23
      cases, compared with 3/8 in nonexpressors. Again, this difference was highly
      significant (P < 0.01). LRP expression before treatment and MDR1 mRNA expression
      after treatment were significantly interrelated (P < 0.001), which might reflect
      the presence of chemoresistant clones liable to metastasize to the regional
      nodes. Persistence of previously detected MDR1-positivity after treatment (7/9
      compared with 0/2 cases) was significantly associated with axillary node
      metastasis (P < 0.05). Finally, in a logistic regression multivariate model,
      histology other than ductal, a Ki67 labeling index of at least 20% and the
      combination of LRP and MDR1 positivity emerged as independent predictors of
      axillary node invasion at the time of rescue mastectomy. CONCLUSION: The
      expression of different genes involved in resistance to chemotherapy, both before
      and after treatment with neoadjuvant, is associated with the presence of axillary
      node invasion at rescue surgery in locally advanced breast cancer. This might
      reflect the presence of intrinsically resistant clones before any form of
      therapy, which persist after it, and could be helpful both for prognosis and for
      the choice of individual treatment.

PMID- 11305956
TI  - The future of urologic research in Canada:

PMID- 11305954
TI  - Allelic loss on chromosome band 18p11.3 occurs early and reveals heterogeneity in
      breast cancer progression.
AB  - We examined the stage specificity and heterogeneity of 18p11 alterations in a
      series of tumors representing 96 microdissected samples. Significant loss of
      heterozygosity (LOH) (63%) was found, with 56% occurring early in ductal
      carcinoma in situ. Although most cases indicated LOH was clonally inherited,
      heterogeneity for 18p LOH occurred in 27% of tumors. When compared with other LOH
      data, 18p LOH was found in conjunction with allelic deletion on 3p, 9p, 17p and
      17q, while 13q, 16q, and 11p were less frequently associated. These analyses
      suggest chromosome 18p11 alteration is a common and early event in breast
      disease.

PMID- 11305957
TI  - Combination medical therapy for symptomatic benign prostatic hyperplasia.
AB  - PURPOSE: The purpose of this study was to evaluate treatment response to
      terazosin, finasteride, or a combination of both in men with symptomatic benign
      prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with BPH were
      consecutively enrolled from a clinical urology practice. International Prostate
      Symptom Score (IPSS), peak urinary flow rate, and prostate volume were assessed
      at baseline and every 2 months for 12 months. Detrusor pressure at maximum flow
      was assessed at baseline, 4 and 12 months. Patients were randomized into 1 of 3
      treatment groups - terazosin alone, finasteride alone, or combination therapy.
      RESULTS: At 12 months, symptom scores had decreased significantly in all 3
      treatment groups (p<0.05). Combination therapy resulted in significantly greater
      reductions in IPSS than terazosin or finasteride (6.4, 4.9, 4.1 points,
      respectively, p<0.05) There were significant increases in peak urinary flow rate
      within each treatment group, although there were no significant changes between
      groups. Detrusor pressure also significantly decreased from baseline within each
      treatment group. Patients treated with combination therapy had a significantly
      greater mean decrease in detrusor pressure after 12 months when compared with
      finasteride-treated patients (16.7 versus 10.5 cm H20, p<0.03). There were no
      significant differences between terazosin and combination therapy or between
      terazosin and finasteride despite the relatively greater decrease in detrusor
      pressure seen in the terazosin group when compared with the finasteride group.
      CONCLUSIONS: Combination medical therapy with finasteride and terazosin provides
      greater symptom relief than monotherapy in men with BPH.

PMID- 11305958
TI  - Meta-analysis and economic evaluation of LH-RH agonists' depot formulations in
      advanced prostatic carcinoma.
AB  - The present study compares the relative efficacy, safety and cost of therapy of
      the following LH-RH agonists: buserelin acetate (Suprefact(R) Depot, Hoechst
      Marion Roussel), goserelin acetate (Zoladex(R) LA, Zeneca Pharma Inc.), and
      leuprolide acetate (Lupron(R) SR Depot, Abbott Laboratories Inc.). To support the
      conduct of a cost-minimization analysis in patients with advanced prostatic
      carcinoma their comparable efficacy and safety was first assessed using a meta
      analysis technique. The absence of statistically significant differences among
      the 2 major end points, survival and progression-free survival was confirmed. The
      cost-minimization analysis for the depot formulations was conducted from the
      perspectives of the provincial formulary and the Ministry of Health, and
      considered 2 time horizons: 1 year, and mean survival time of 2.5 years. Cost
      differences among LH-RH agonists were sensitive to changes in dosing interval and
      patient survival time but, even when these parameters were varied, for a general
      population of patients with advanced prostate cancer, buserelin remained the most
      cost-saving treatment alternative among LH-RH agonists.

PMID- 11305955
TI  - Low frequency of E-cadherin alterations in familial breast cancer.
AB  - In order to explore the possible role of E-cadherin in familial cancer, 19
      familial breast cancer patients, whose tumours demonstrated loss of
      heterozygosity (LOH) at the E-cadherin locus, were screened for germline
      mutations. No pathogenic germline alterations were detected in these individuals.
      However, a somatic mutation was found (49-2A-->C) in one of the tumours. This
      tumour showed a pattern of both ductal and lobular histology. Another 10 families
      with cases of breast, gastric and colon cancer were also screened for germline
      mutations, and no mutations were found. A missense mutation in exon 12 of E
      cadherin (1774G-->A; Ala592Thr) was previously found in one family with diffuse
      gastric cancer, and colon and breast cancer. An allelic association study was
      performed to determine whether the Ala592Thr alteration predisposes to breast
      cancer. In total, we studied 484 familial breast cancer patients, 614 sporadic
      breast cancer patients and 497 control individuals. The frequencies of this
      alteration were similar in these groups. However, a correlation between the
      Ala592Thr alteration and ductal comedo-type tumour was seen. These results,
      together with previously reported studies, indicate that germline mutations and,
      more commonly, somatic mutations in E-cadherin may have an influence on the
      behaviour of the tumours, rather than predispose to breast cancer.

PMID- 11305959
TI  - Renal cell carcinoma metastatic to the contralateral ureter.
AB  - The ureter is an uncommon location for cancer metastases, the majority of which
      are due to nonurologic cancers such as stomach and breast.(1) Renal cell
      carcinoma (RCC) metastatic to the ureter has been reported infrequently. We
      report a case of metachronous metastatic RCC to the contralateral ureter.

PMID- 11305960
TI  - Acute appendicitis presenting as priapism in an 8 year old.
AB  - Priapism is uncommon in children. When it does occur the etiology is usually
      leukemia, sickle cell disease, or trauma.(1) We present a case of priapism in a
      child in whom the underlying etiology was acute appendicitis. To our knowledge,
      this has never been reported in the literature.

PMID- 11305961
TI  - Primary extranodal perirenal malignant lymphoma.
AB  - We report 2 cases of primary extranodal perirenal malignant lymphoma. Complete
      examination of the retroperitoneum confirmed that the disease was confined to the
      perirenal space and was not associated with nodal or other body site involvement.
      Previous reports of perirenal lymphoma in the medical literature have based
      diagnosis on either radiologic findings and past history of malignant lymphoma
      with or without needle biopsy of the retroperitoneum. Due to circumscription of
      this lesion by the renal capsule and Gerota's capsule and isolated perirenal
      findings in early disease, perirenal lymphoma may mimic a renal neoplasm on
      clinical and radiologic examinations.

PMID- 11305962
TI  - Antegrade continence enema for adult neurogenic patients.
AB  - Urologists often care for adult patients with neurogenic bladder. Adult patients
      with neurogenic bladder may have concommitant neurogenic bowel. Neurogenic bowel
      may be refractory to conservative management. The Malone antegrade continence
      enema (ACE) has been successful in pediatric neurogenic bowel. Little experience
      has been described among adult neurogenic bowel patients. We describe the
      technique of the ACE and review our results for adult neurogenic bowel.

PMID- 11305963
TI  - EDITORIAL.

PMID- 11305964
TI  - Stability of reconstituted freeze-dried Bacille Calmette-Guerin used for
      intravesical immunotherapy for bladder cancer.
AB  - The product monographs for the commercially available products of Bacille
      Calmette-Guerin (BCG) state they must be used immediately following
      reconstitution. We hypothesized that the viability of the reconstituted
      preparations of BCG would not be altered for a period of up to 4 hours thus
      allowing a longer time interval between full preparation and its intravesical
      administration. Vials of freeze-dried ImmuCysttrade mark (Connaught Laboratories)
      and TICEtrade mark BCG (Organon-Teknika) were fully reconstituted in
      approximately 50 ml of saline and aliquots of the fully reconstituted product
      were serially diluted and inoculated onto freshly prepared Lowenstein-Jensen
      slants and colony counts were conducted at 0, 2, and 4 hours. The colony counts
      of the freeze-dried preparations of BCG varied between 0.1 and 0.3 x 108 and
      between 0.6 and 1.1 x 108 per reconstituted volume at 4 hours for the Connaught
      and TICE strains, respectively. There was no decrease in the colony counts
      between 0 and 4 hours for either product. There were no significant differences
      in the viability of the fully reconstituted freeze-dried preparation of BCG for
      up to 4 hours after complete reconstitution. These findings would suggest some
      latitude may be provided for institutions where the product is fully
      reconstituted prior to its actual administration.

PMID- 11305965
TI  - Relative accuracy of renal scan in estimation of renal function during partial
      ureteral obstruction.
AB  - This study is designed to evaluate the relative ability of DMSA and DTPA renal
      scans to accurately reflect differential renal function (DRF) compared with
      inulin clearance in the presence of partial unilateral ureteral obstruction. DRF
      was determined in 29 young rabbits by both renal scans. In the experimental group
      (n=21), left partial ureteral obstruction was created. Following 8 to 24 weeks,
      individual renal function in the obstructed animals were assessed by both renal
      scans and clearance of inulin. Eight animals were used as control. In the control
      group, DRF measured by DMSA, but not DTPA, correlated well with inulin clearance.
      Both scans documented a significant change in the DRF of the obstructed group
      (p<0.001). In the partially obstructed kidneys DRF derived by inulin was
      significantly lower than that measured by DMSA or DTPA scans (p<0.001 and
      p<0.0001). DRF measured by DMSA correlates well with inulin clearance in the
      control group. A similar correlation was not obtained by DMSA in the presence of
      obstruction. DTPA does not correlate with inulin clearance either in the control
      or the obstructed group.

PMID- 11305966
TI  - Progression of prostate cancer despite undetectable serum prostate specific
      antigen.
AB  - The serum prostate specific antigen (PSA), having been a valid marker for
      prostate cancer in 2 patients at the time of their diagnosis, ultimately became
      undetectable (<0.1 ng/ml) despite evidence of disease progression. This was
      documented by isotope bone scans and the results of subsequent CT guided bone
      biopsies. In both biopsy specimens, immunohistochemical staining for PSA was
      negative, but positive for prostate acid phosphatase after microwave antigen
      enhancement. In both cases the serum prostate acid phosphatase (PAP) had remained
      within normal limits. We would caution that prostate cancer may recur and
      progress with an undetectable serum PSA after antiandrogen therapy.

PMID- 11305967
TI  - Perinephric abscess following extracorporeal shockwave lithotripsy.
AB  - Since the introduction and widespread use of extracorporeal shockwave lithotripsy
      (SWL), various complications have been noted. Perinephric hematoma and ureteral
      obstruction may be anticipated by urologists as potential problems. We report the
      first case of perinephric abscess encountered after 17 895 SWL treatments at our
      institution. A 65 year old woman presented 4 months following a second SWL
      procedure with a perinephric abscess and was successfully treated with
      percutaneous drainage. A review of the English literature revealed only 3 other
      cases of perinephric abscess following SWL. This diagnosis should be considered
      in early and late presentations of flank pain following SWL.

PMID- 11305968
TI  - Combined percutaneous and endoscopic management of the distally ligated ureter.
AB  - While combined percutaneous and endoscopic techniques have been described
      previously as a means of dealing with the distally strictured ureter, this report
      confirms that these approaches can also be used successfully in the management of
      the very distally ligated ureter in the early post-injury period.

PMID- 11305969
TI  - Differences in outcome between percutaneous coronary intervention and coronary
      bypass grafting.

PMID- 11305971
TI  - The risk of congestive heart failure: sobering lessons from the Framingham Heart
      Study.
AB  - This review highlights recent contributions of the Framingham Heart Study to our
      understanding of the epidemiology of congestive heart failure (CHF). Given its
      uniform criteria for the diagnosis of CHF and its long duration of follow-up, the
      Framingham study has had a unique perspective on the short- and long-term risk of
      developing CHF, its predisposing risk factors, and its prognosis in a general,
      community-based population. Some recent studies from Framingham have provided
      important insights on CHF: the lifetime risk is estimated to be 20% for men and
      women; hypertension is the most important modifiable risk factor, with a
      population-attributable risk of CHF of 59% for women and 39% for men; a clinical
      prediction rule for development of CHF has recently been published; and the
      prognosis after development of CHF is grim, with a median survival of 1.7 years
      in men and 3.2 years in women.

PMID- 11305972
TI  - Heart failure in blacks: etiologic and epidemiologic differences.
AB  - Heart failure in black Americans has become a cardiovascular conundrum of
      increasing clinical significance. Over 60% of black patients with heart failure
      have an antecedent history of hypertension as a putative cause of left
      ventricular (LV) dysfunction, whereas only 30% have coronary artery disease as
      the suspected cause of LV dysfunction. Once affected with heart failure, the
      natural history of the disease becomes worrisome: LV dysfunction is more
      advanced, the severity of the disease is worse, the hospitalization rate is
      higher, and the mortality rate is at least 30% higher than that of white
      Americans. When treated in a conventional manner, available data have been
      inconsistent, and reliable drug efficacy has not been demonstrated. These
      differences do not appear to be due to socioeconomic factors. It is quite
      possible that unique pertubations in the neurohormonal environment may explain
      differences in the natural history of heart failure in blacks and yield new
      targets of therapy.

PMID- 11305973
TI  - Genomics and the pathophysiology of heart failure.
AB  - Heart failure is not a single disease entity, but a syndrome with various causes,
      including hypertension, ischemic and congenital heart disease, cardiomyopathy,
      and myocarditis. Because of the multiple etiologies and secondary adaptations
      contributing to heart failure, the study of the cellular and molecular mechanisms
      underlying the development and progression of this syndrome has been rather
      challenging. Much has been learned about the remodeling processes in heart
      failure, which involve complex interactions among numerous mediators in signaling
      and regulatory pathways. The Human Genome Project and related projects have
      provided a preliminary database for a genome-wide analysis of complex polygenic
      disorders such as heart failure. With the aid of expressed sequence tag
      technology and microarray applications, both known and previously uncharacterized
      genes involved in the induction and regression of cardiac hypertrophy and its
      progression to heart failure can be analyzed simultaneously. Deciphering the
      complexity of sequence-structure-function relationships in heart failure is a
      goal for the future, and will require advances in structural biology, proteomics,
      and computational technology. In this review, we summarize the cellular and
      molecular aspects of heart failure, and how recent applications of genomic
      technologies have been successful in achieving a more complete portrait of gene
      expression in this pathologic state.

PMID- 11305974
TI  - Novel neurohumoral factors in congestive heart failure: adrenomedullin.
AB  - Adrenomedullin is a 52-amino acid peptide that circulates in human plasma. The
      plasma concentrations of the peptide are increased in cardiovascular disease in
      proportion to the degree of hemodynamic impairment. Plasma adrenomedullin levels
      in heart failure, and in subjects with acute myocardial infarction, have been
      shown to convey independent prognostic information. Adrenomedullin has multiple
      biologic effects, but characteristically causes vasodilatation. The actions of
      adrenomedullin and the activation of this peptide in cardiovascular disease
      suggest it may have an important pathophysiologic role in heart failure.
      Manipulation of adrenomedullin or its receptor may have therapeutic potential.

PMID- 11305976
TI  - Therapeutic options in patients with reduced ejection fraction and nonsustained
      ventricular tachycardia.
AB  - The patient with a reduced ejection fraction and nonsustained ventricular
      tachycardia represents a common management problem for the physician. This
      article reviews the supporting evidence for the therapeutic options available for
      these patients according to the etiology of the reduced ejection fraction. In
      postinfarction patients, electrophysiology-guided implantable cardioverter
      defibrillator therapy improves survival more than antiarrhythmic therapy. In
      patients with nonischemic cardiomyopathy, the best therapy is yet undetermined.
      Ongoing clinical trials will hopefully direct future therapy.

PMID- 11305977
TI  - Low-level inotropic stimulation with type III phosphodiesterase inhibitors in
      patients with advanced symptomatic chronic heart failure receiving beta-blocking
      agents.
AB  - beta-blocking agents are now well established as a cornerstone therapy in mild to
      moderate heart failure. Patients with more advanced heart failure depend on
      adrenergic activation to maintain adequate myocardial function. This leads to
      significant difficulties in using beta-blockers in advanced or severe heart
      failure. In addition, recent data indicate that adrenergic withdrawal might be
      detrimental in some of these patients. In higher doses, positive inotropic agents
      have been shown to increase mortality when used alone in subsets with advanced
      heart failure. Preliminary data suggest that the combination of low-dose
      phosphodiesterase inhibitors and a beta-blocker may be better tolerated and does
      not appear to be associated with the adverse effects of either therapy used
      alone. We discuss the theoretic underpinning of this approach and the supportive
      clinical data.

PMID- 11305978
TI  - The role of endothelin receptor antagonists in the treatment of chronic heart
      failure.
AB  - A role of the potent and long-acting vasoconstrictor peptide endothelin-1 in the
      pathophysiology of chronic human heart failure has been postulated based on
      indirect evidence such as elevated plasma endothelin-1 levels, their correlation
      with the degree of hemodynamic impairment, and their predictive value for patient
      survival. The advent of specific of endothelin-1 receptor antagonists has
      provided the opportunity to directly evaluate its pathophysiologic role and
      assess its potential role as a new approach to heart failure therapy. This review
      summarizes the evidence linking endothelin-1 to the pathophysiology of chronic
      heart failure, and analyzes the clinical results obtained thus far in patients
      during acute intravenous, and more prolonged, oral administration of endothelin-1
      receptor antagonists.

PMID- 11305979
TI  - Mitral ring annuloplasty: an incomplete correction of functional mitral
      regurgitation associated with left ventricular remodeling.
AB  - Functional mitral regurgitation (FMR) occurs commonly in patients undergoing left
      ventricular (LV) remodeling. It is ubiquitous in patients referred to cardiac
      transplantation for LV systolic dysfunction and predicts a poor prognosis. The LV
      remodeling that is responsible for FMR is well understood and involves regional
      LV dysfunction Mitral annular dilatation is present in patients with idiopathic
      dilated cardiomyopathy but most often absent in patients with ischemic
      cardiomyopathy. Nonrandomized observations indicate that implantation of a mitral
      undersized flexible mitral ring reduces the amount of FMR, reverses LV
      remodeling, and improves symptoms in patients with end-stage cardiomyopathy and
      severe FMR. Whether a surgical procedure that does not correct the major LV
      alterations leading to FMR can have long-lasting effects on the amount of FMR and
      the reversal of LV remodeling remains to be demonstrated in randomized trials.

PMID- 11305980
TI  - The angiotensin-converting enzyme inhibitor and aspirin interaction in congestive
      heart failure: fear or reality?
AB  - Angiotensin-converting enzyme (ACE) inhibitors have become the cornerstone of
      therapy for congestive heart failure (CHF). Because ischemic heart disease is the
      most common cause of CHF, aspirin is frequently given concomitantly with ACE
      inhibitors in patients with CHF. Increased bradykinin levels, with the consequent
      enhanced synthesis of vasodilatory prostaglandins, appear to mediate a
      significant benefit of ACE inhibitor therapy in these patients. In contrast,
      aspirin inhibits cyclooxygenase, and thereby suppresses prostaglandin production.
      Thus, these counteracting effects on prostaglandins may result in antagonism
      between ACE inhibitor and aspirin therapy in heart failure patients. Several
      early reports questioned the safety of aspirin in CHF, and the potential
      antagonistic interaction between ACE inhibitors and aspirin in patients with
      heart failure has become the focus of both increasing research and intense
      debate. This article briefly highlights the theoretic considerations underlying
      this interaction, and reviews the available evidence for such an interaction from
      clinical trials.

PMID- 11305982
TI  - Effect of exercise intensity and frequency on lipid levels in men with coronary
      heart disease: Training Level Comparison Trial.
AB  - The objective of the Training Level Comparison Trial was to determine whether a
      more intense exercise program versus a less intensive program has additional
      favorable effects on blood lipids in men with coronary heart disease (CHD) over a
      12-month period. The study-a randomized, controlled trial conducted at 2 clinical
      centers-enrolled 185 patients with documented CHD. A simple randomization
      procedure led to unequal numbers of patients in the 2 interventions: 82 in the
      low-intensity and 103 in the high-intensity group. Target heart rate during
      exercise corresponded to 50% of maximum oxygen uptake (VO(2 max)) +/- 5 beats/min
      in the low-intensity group and 85% +/- 5 beats/min in the high-intensity group.
      The intensity of exercise made little difference on lipid improvements. However,
      the attendance rates for the 6- and 12-month periods (percentage of total
      exercise sessions attended) were significantly related to increased high-density
      lipoprotein (HDL) cholesterol (r(s) [Spearman rank correlation coefficient 0.20
      to 0.26, p <0.05]), and decreases in the ratios of low-density lipoprotein (LDL)
      to-HDL cholesterol (LDL:HDL, r(s) = -0.24 to -0.28, p < 0.01) and total-to-HDL
      cholesterol (total:HDL, r(s) = -0.25 to -0.29, p < 0.01) at 6 and 12 months. The
      relation of the attendance rate to LDL:HDL and total:HDL ratios remained
      significant in repeated-measures regression analysis. Exercise frequency may be
      more important than intensity in improving HDL cholesterol and LDL:HDL and
      total:HDL ratios in men with CHD.

PMID- 11305981
TI  - Detailed angiographic analysis of women with suspected ischemic chest pain (pilot
      phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE]
      Study Angiographic Core Laboratory).
AB  - The purpose of this study is to provide a contemporary qualitative and
      quantitative analysis of coronary angiograms from a large series of women
      enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study who had
      suspected ischemic chest pain. Previous studies have suggested that women with
      chest pain have a lower prevalence of significant coronary artery disease (CAD)
      compared with men. Detailed analyses of angiographic findings relative to risk
      factors and outcomes are not available. All coronary angiograms were reviewed in
      a central core laboratory. Quantitative measurement of percent stenosis was used
      to assess the presence and severity of disease. Of the 323 women enrolled in the
      pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had
      significant ( > 50% diameter stenosis) CAD. Of those with significant CAD, most
      had multivessel disease. Features suggesting complex plaque were identified in <
      10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI),
      current hormone replacement therapy, and unstable angina were all significant,
      independent predictors of presence of significant disease (p < 0.05). Subsequent
      hospitalization for a cardiac cause occurred more frequently in those women with
      minimal and significant disease compared with no disease (p = 0.001). The common
      findings of no and extensive CAD among symptomatic women at coronary angiography
      highlight the need for better clinical noninvasive evaluations for ischemia.
      Women with minimal CAD have intermediate rates of rehospitalization and
      cardiovascular events, and thus should not be considered low risk.

PMID- 11305983
TI  - Difference in the mortality of the CABRI diabetic and nondiabetic populations and
      its relation to coronary artery disease and the revascularization mode.
AB  - In diabetics with coronary artery disease (CAD), there remains uncertainty as to
      whether revascularization by percutaneous transluminal coronary angioplasty
      (PTCA) or coronary artery bypass surgery (CABG) is preferable. To address this, 4
      year mortality and level of pre- and postrevascularization angiographic CAD
      (measured by a series of coronary scores) were compared between both diabetics
      and nondiabetics and between revascularization modes in the Coronary Angioplasty
      versus Bypass Revascularization Investigation population as a whole, and then
      substratified by diabetic status and then by procedure to which they were
      randomized. The 1,054 randomized subjects contained 125 diabetics (11.9%) who had
      significantly greater mortality than nondiabetics (RR 2.19, p = 0.001). Among
      diabetics or nondiabetics, there was no significant mortality difference between
      those randomized to PTCA versus those to CABG. Diabetics randomized to PTCA and
      those to CABG had higher mortalities than respective nondiabetics; the
      association reached significance only in the former (RR 2.41, p = 0.002). All
      subgroups had similar prerevascularization CAD. Postrevascularization residual
      CAD was consistently significantly greater in PTCA than in respective CABG
      subgroups. Most measurements of CAD were greater in diabetic than in nondiabetic
      subgroups, but none was significant. In the Coronary Angioplasty versus Bypass
      Revascularization Investigation, diabetics had double the mortality of
      nondiabetics; this difference was statistically significant both for the entire
      population and for those randomized to PTCA, but not for those randomized to
      CABG. Among diabetics or nondiabetics, there was no significant mortality
      difference between PTCA and CABG. The higher diabetic mortality was more likely
      related to more rapid disease progression than to greater postrevascularization
      disease.

PMID- 11305984
TI  - Determinants and prognostic significance of spontaneous coronary recanalization
      in acute myocardial infarction.
AB  - Spontaneous recanalization (SR) occurs after the onset of acute myocardial
      infarction (AMI), but its clinical significance in the reperfusion era remains
      uncertain. We evaluated the determinants and prognostic significance of SR in 196
      consecutive patients with AMI who underwent primary angioplasty at our
      institution. The study population was divided into 2 groups according to the
      presence (group I, n = 44) or absence (group II, n = 152) of SR (Thrombolysis In
      Myocardial Infarction [TIMI] anterograde > or = 2 flow on the preintervention
      angiogram). The primary end point was the occurrence, within 6-weeks after AMI,
      of death, nonfatal reinfarction, and congestive heart failure. Baseline
      characteristics were similar between the 2 groups. Peak levels of creatine kinase
      were lower in group I than in group II (2,500 +/- 1,800 vs 4,000 +/- 2,900 U/L,
      respectively, p < 0.05). The rate of TIMI flow grade 3 after intervention was
      higher in group I than in group II (93.2% vs 79.6%, respectively, p < 0.05), and
      patients in group I had a faster corrected TIMI frame count than those in group
      II (22.7 +/- 12.4 vs 30.3 +/- 22.8, respectively, p < 0.05). Preinfarction angina
      (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.10 to 4.33, p < 0.05),
      heavy thrombi (OR 0.10, 95% CI 0.01 to 0.74, p < 0.05), and good angiographic
      collaterals (OR 0.12, 95% CI 0.02 to 0.89, p < 0.05) were independent predictors
      of SR. Death, reinfarction, and severe arrhythmia were not different between the
      2 groups. However, heart failure occurred more frequently in group II than in
      group I (15.1% vs 2.3%, respectively, p < 0.05). The primary end point was also
      significantly lower in group I than in group II (4.5% vs 18.4%, respectively, p <
      0.05). In conclusion, SR in AMI is associated with faster coronary flow, smaller
      infarct size, and a better clinical outcome after primary angioplasty.

PMID- 11305985
TI  - Early patency of the infarct-related artery after myocardial infarction preserves
      diastolic filling.
AB  - A patent infarct-related artery (IRA) following myocardial infarction has been
      associated with lower mortality, increased systolic function, decreased left
      ventricular remodeling, and electrical stability. The purpose of this study was
      to determine whether coronary artery patency early after myocardial infarction is
      associated with greater early diastolic filling than a closed artery.
      Radionuclide ventriculograms were performed at a central laboratory on 167
      patients who received alteplase for an acute myocardial infarction and had
      infarct artery patency determined by cardiac catheterization. The peak early
      filling rate (PEFR) was assessed by 4 different methods: (1) PEFR (EDV/s)-
      normalized to the end-diastolic volume; (2) PEFR (SV/s)--normalized to the stroke
      volume; (3) PEFR (ml/s/m(2))--an absolute diastolic filling rate; and (4) PEFR
      (PER)--normalized to the peak ejection rate. Patients with a closed IRA (n = 16,
      Thrombolysis In Myocardial Infarction [TIMI] 0 or 1 flow) and patients with an
      open IRA (n = 151, TIMI 2 or 3 flow) had similar ages, ejection fractions, and
      cardiac volumes. However, among patients with an occluded IRA, the PEFR was
      decreased by 12% to 18% by the 4 measures of diastolic filling (3 of 4 methods, p
      <0.05). PEFR (EDV/s) was 1.69 +/- 0.9 in the occluded group versus 2.06 +/- 0.4
      EDV/s in the open artery group (p = 0.005). By multivariate analysis, IRA patency
      was an independent predictor of the PEFR by all 4 methods. Early coronary artery
      patency after an acute myocardial infarction preserves diastolic filling.
      Improved diastolic function may in part explain part of the long-term benefits of
      a patent IRA after thrombolytic therapy when there is no documented improvement
      in the ejection fraction.

PMID- 11305986
TI  - Correlation of ST-segment depression during ambulatory electrocardiographic
      monitoring with myocardial perfusion and left ventricular function.
AB  - To assess the relation between silent ischemia and objective markers of ischemia
      we compared ambulatory electrocardiographic (AECG) monitoring, exercise stress
      testing, and technetium-99m methoxyisobutyl isonitrile single-photon emission
      computed tomography (SPECT) in 68 patients with coronary artery disease. ST
      segment depression at AECG monitoring occurred in 40%, exercise testing was
      positive in 88%, and SPECT was abnormal in 98% of patients. Patients with ST
      segment depression had a higher incidence of 3-vessel disease (70% vs 45%, p =
      0.04), shorter duration of exercise (267 +/- 109 vs 416 +/- 167 seconds, p <
      0.01), lower workload achieved (5.1 +/- 1.9 vs 7.6 +/- 2.8 METs, p < 0.0002), and
      a greater extent of ischemia at scintigraphy (p = 0.01). Patients with a total
      ischemic time of >30 minutes in a 24-hour period had a lower ejection fraction
      (48 +/- 21% vs 70 +/- 9%, p = 0.001), a higher perfusion index at rest (2.4 +/-
      0.6 vs 1.6 +/- 0.6, p = 0.001), and a greater number of segments with fixed
      perfusion defects (4.1 +/- 3.7 vs 1.3 +/- 1.8, p = 0.02) in comparison with those
      who had a shorter ischemic time. We conclude that AECG monitoring fails to
      identify a substantial proportion of patients with objective markers of ischemia;
      however, ST-segment depression reflects more significant disease. Longer total
      ischemic time correlates with the area of myocardial damage but not with other
      markers of ischemia.

PMID- 11305987
TI  - Changes in the practice of percutaneous coronary intervention: a comparison of
      enrollment waves in the National Heart, Lung, and Blood Institute (NHLBI) Dynamic
      Registry.
AB  - The National Heart, Lung, and Blood Institute Dynamic Registry includes 15
      clinical sites in wave 1, and 16 sites in wave 2 as well as a data-coordinating
      center. The first wave of enrollment began in July 1997 and was completed in
      February 1998. The second wave began in February 1999 and ended in June 1999.
      There were a total of 2,526 patients in wave 1 and 2,109 patients in wave 2.
      Comprehensive pre-, intra-, and postprocedure (in-hospital) data were analyzed
      for changes between recruitment waves. Patients in wave 2 were more frequently
      nonwhite (p < or = 0.001), hypertensive by history (p < or = 0.001), had more
      significant noncardiac comorbidity (p < or = 0.01), and had more frequently
      undergone prior percutaneous coronary intervention (p < 0.05). Patients in wave 2
      underwent percutaneous coronary intervention in a setting of acute coronary
      syndromes more frequently than wave 1 patients (p < or = 0.001). However, most
      interventions in both waves were performed on 1 vessel, irrespective of the
      extent of disease. Attempted lesions in wave 2 were longer (p < or = 0.001), less
      frequently totally occluded (p < or = 0.001), and more frequently in vessels with
      a prior stent (p < or = 0.01). Using the American Heart Association/American
      College of Cardiology lesion classification scheme, attempted lesions in wave 2
      were less complex than those in wave 1 (p < or = 0.001). Stent use increased
      significantly from wave 1 (67%) to wave 2 (79%, p < or = 0.001) as did the use of
      platelet glycoprotein IIb/IIIa antagonists (wave 1, 24%; wave 2, 32%: p < 0.001).
      Procedural outcomes (angiographic success without major in-hospital adverse
      events) were excellent in both waves 1 (94.6%) and 2 (95.6%) and were not
      significantly different. However, the frequency of significant procedural
      coronary dissection and in- and out-of-laboratory abrupt closure were
      significantly less in wave 2 (p < or = 0.001) Discharge medications were more
      likely to include angiotensin-converting enzyme inhibitors, beta-adrenergic
      blocking agents, and hypolipidemic treatment in wave 2 than in wave 1 (p < or =
      0.001). These data indicate a continuing aggressive approach to patient care over
      the time interval analyzed. Although overall procedural outcomes are excellent,
      procedural safety has been further enhanced. There is also a growing awareness of
      the importance of secondary prevention among interventional cardiologists.

PMID- 11305988
TI  - New electrocardiographic criteria for posterior wall acute myocardial ischemia
      validated by a percutaneous transluminal coronary angioplasty model of acute
      myocardial infarction.
AB  - The standard 12-lead electrocardiogram (ECG) fails to detect ST-segment elevation
      in patients with posterior wall acute myocardial ischemia. However, additional
      posterior leads V(7-9) provide limited additional diagnostic information to the
      standard 12-lead ECG when an ischemic criterion of 1-mm ST elevation is used. No
      study is available to delineate the ischemic criteria in the posterior
      electrocardiographic leads. Continuous 15-lead ECGs (standard 12 lead + V(7-9))
      were recorded in 53 subjects undergoing elective left circumflex coronary
      angioplasty (posterior ischemia model). ST amplitudes (J + 60 ms) at
      preangioplasty baseline were subtracted from maximal ST amplitudes during balloon
      occlusion to create a positive or negative change score (DeltaST) for each of the
      15 leads. During 53 left circumflex occlusions, 26 subjects (49%) had DeltaST
      elevation of > or = 1 mm and 24 subjects (45%) had DeltaST elevation ranging from
      0.5 to 0.95 mm in > or = 1 posterior leads. Five subjects (9%) had DeltaST
      elevation of > or = 1 mm in the posterior leads without DeltaST elevation
      anywhere in any of the 12 leads. The sensitivity in detecting myocardial ischemia
      using 15-lead ECGs (58%) was not statistically different from the standard 12
      lead ECG (49%) (p = 0.06). Adjusting the ischemic criterion from 1 to 0.5 mm in
      V(7-9) significantly improved the sensitivity from 49% in the 12-lead ECG to 94%
      in the 15-lead ECG (p = 0.000). In addition, 12 subjects (23%) had posterior ST
      segment elevation without anterior ST-segment depression. Thus, posterior leads
      V(7-9) contribute significant additional diagnostic information above and beyond
      the standard 12-lead ECG only when a new ischemic criterion of 0.5 mm instead of
      1 mm ST elevation is applied to the posterior leads.

PMID- 11305989
TI  - Long-term clinical outcome of patients with prior myocardial infarction after
      palliative radiofrequency catheter ablation for frequent ventricular tachycardia.
AB  - Patients with coronary artery disease and hemodynamically tolerated, highly
      frequent, sustained monomorphic ventricular tachycardia (VT) may undergo
      radiofrequency catheter ablation (RFCA) for elimination of > or = 1
      morphologically distinct VTs. The purpose of this study was to evaluate the long
      term clinical benefit following RFCA as a palliative treatment of highly frequent
      or incessant ischemic VT. Fifty-five patients underwent RFCA of 62 VTs. The
      target VT was successfully ablated in 82% of patients. Complication and
      perioperative mortality rates were 7.2% and 1.8%, respectively. At 5 years, total
      mortality was 51% and probability of freedom from all ventricular
      tachyarrhythmias was 28%. All patients had highly frequent or incessant drug
      refractory VT before RFCA. Clinical benefit was defined as either freedom from
      all ventricular tachyarrhythmias, or a reduction in frequency of recurrence from
      > 1 episode per month before RFCA to < or = 1 episode per year of any ventricular
      tachyarrhythmia, including all appropriate implantable cardioverter defibrillator
      (ICD) therapies. By this definition, 54% of the patients continued to benefit
      from RFCA at 5 years. Of 19 variables analyzed with a Cox univariate model, only
      the presence of a left ventricular aneurysm and a previously implanted ICD were
      predictive of any ventricular arrhythmia recurrence. However, at 5 years over
      half of the surviving patients still continued to benefit from RFCA of their
      clinical VT. Because the overall rate of any ventricular tachyarrhythmia
      occurrence during follow-up is high, additional protection, such as an ICD, is
      required.

PMID- 11305990
TI  - Gender differences in systolic left ventricular function in hypertensive patients
      with electrocardiographic left ventricular hypertrophy (the LIFE study).
AB  - Echocardiography was performed in 944 untreated hypertensive patients (391 women
      and 553 men, mean age 66 years) who had electrocardiographic left ventricular
      (LV) hypertrophy at baseline in the Losartan Intervention For End point reduction
      in hypertension (LIFE) study to evaluate gender-associated differences in
      systolic LV function. Women had significantly lower diastolic blood pressure
      (175/97 vs 173/99 mm Hg) and body surface area and a higher body mass index (all
      p < 0.01). Women also had higher LV ejection fraction (EF), endocardial and
      midwall fractional shortening (63% vs 60%, 35% and 33%, and 16% vs 15%,
      respectively, all p < 0.01), higher stress-corrected midwall fractional
      shortening (98% vs 96%, p < 0.05), and lower circumferential end-systolic wall
      stress (178 vs 187 kdynes/cm(2), p < 0.01). There was no difference in age or LV
      mass indexed for height(2.7), but relative wall thickness was higher in women
      (0.42 vs 0.41, p < 0.05). In multiple regression analyses: (1) EF and endocardial
      fractional shortening were 2% to 3% higher in women than men, independent of the
      effects of LV stress, body mass index, and height (multiple r = 0.77 and 0.75,
      respectively, gender p < 0.02 in both models); (2) midwall fractional shortening
      was 0.5% higher in women, independent of the effects of age, body mass index,
      circumferential end-systolic stress, and absence of diabetes (multiple r = 0.36,
      p = 0.014 for gender); and (3) stress-corrected LV midwall fractional shortening
      was 2% higher (p = 0.004) in women, independent of the effects of age, height,
      heart rate, body mass index, and diabetes (multiple r = 0.33). Thus, female
      gender is an independent predictor of higher systolic LV function in hypertensive
      patients with electrocardiographic LV hypertrophy.

PMID- 11305991
TI  - Cost-effectiveness analysis of long-term moderate exercise training in chronic
      heart failure.
AB  - The purpose of this study is to perform a cost-effectiveness analysis of long
      term moderate exercise training (ET) in patients with stable chronic heart
      failure. In particular, the study focuses on the survival analysis and cost
      savings from the reduction in the hospitalization rate in the exercise group. In
      the past 10 years, ET has been shown to be beneficial for patients with stable
      class II and III heart failure in many randomized clinical trials. However, the
      cost-effectiveness of a long-term ET program has not been addressed for outcomes
      related to morbidity/mortality end points or health care utilization. We examined
      the cost-effectiveness of a 14-month long-term training in patients with stable
      chronic heart failure. The estimated increment cost for the training group,
      $3,227/patient, was calculated by subtracting the averted hospitalization cost,
      $1,336/patient, from the cost of ET and wage lost due to ET, estimated at
      $4,563/patient. For patients receiving ET, the estimated increment in life
      expectancy was 1.82 years/person in a time period of 15.5 years, compared with
      patients in the control group. The cost-effectiveness ratio for long-term ET in
      patients with stable heart failure was thus determined at $1,773/life-year saved,
      at a 3% discount rate. Long-term ET in patients with stable chronic heart failure
      is cost-effective and prolongs survival by an additional 1.82 years at a low cost
      of $1,773 per/life-year saved.

PMID- 11305992
TI  - Association between selective serotonin-reuptake inhibitor therapy and heart
      valve regurgitation.
AB  - The identification of an association between fenfluramines and valvular disease
      has raised the possibility of a similar association between another class of
      medications that increases local levels of serotonin, the selective serotonin
      reuptake inhibitors (SSRIs). The objective of this study was to examine the
      association between heart valve regurgitation and treatment with SSRIs. We
      examined 5,437 consecutive patients who underwent echocardiography. Patients with
      a similar likelihood of SSRI treatment were identified by propensity models. The
      prevalence of regurgitation according to treatment was compared after adjusting
      for clinical characteristics associated with regurgitation. We also blindly
      reinterpreted a subset of 2,000 echocardiograms to identify characteristics
      associated with fenfluramine-associated valvular heart disease such as posterior
      mitral leaflet restriction. Among 5,437 consecutively hospitalized patients, we
      identified 292 who had taken SSRIs before admission. Patients taking SSRIs tended
      to be younger, female, Caucasian, unmarried, and more likely to have psychiatric
      illness and hypertension (p < or = 0.05). The overall prevalence of regurgitation
      meeting Food and Drug Administration criteria (at least moderate mitral
      regurgitation or mild aortic regurgitation) was 30%, with no significant
      difference in prevalence between those receiving SSRIs (26.7%) and controls
      (30.4%) (p = 0.19). The association remained negative when comparing SSRI-treated
      patients to controls with similar characteristics. Furthermore, the prevalence of
      features described in conjunction with fenfluramine exposure, such as posterior
      mitral leaflet restriction, was not higher in SSRI-treated patients. Among a
      large consecutive cohort of patients, the prevalence of mitral and aortic
      regurgitation in patients taking SSRIs was not different from that of controls,
      suggesting that SSRIs are not associated with valvular disease.

PMID- 11305993
TI  - Mitigation of the clinical significance of spurious elevations of cardiac
      troponin I in settings of coronary ischemia using serial testing of multiple
      cardiac markers.
AB  - The ability to differentiate between true positives, false positives, and
      sporadically elevated cardiac troponin levels has grown in importance as cardiac
      troponins assume an increasingly dominant role in the diagnosis of coronary
      syndromes. In a population sample of 1,000 patients who presented consecutively
      to a large urban hospital emergency room, 50 of 112 patients who had elevated
      troponin levels (> 0.6 ng/ml) during evaluation for myocardial injury were
      subsequently found to have had an isolated, spurious elevation of cardiac
      troponin, and not a diagnosed myocardial infarction. Logistic regression analysis
      shows that by hierarchically analyzing electrocardiographic changes with
      concurrent creating kinase-MB and myoglobin levels at the time of the troponin
      elevation, one may predict with 91% accuracy whether the troponin elevation is
      actually indicative of a myocardial infarction in a patient. Spurious troponin
      elevations may be a common occurrence, and if not detected, may result in an
      increased number of falsely diagnosed myocardial infarctions.

PMID- 11305994
TI  - Lipid lowering and weight reduction by home-delivered dietary modification in
      coronary heart disease patients taking statins.

PMID- 11305995
TI  - Association between plasma folate and coronary disease independent of
      homocysteine.

PMID- 11305996
TI  - Association of elevation of anti-Helicobacter pylori antibody with myocardial
      ischemic events in coronary artery disease.

PMID- 11305997
TI  - A simple, readily available method for risk stratification of patients with
      unstable angina and non-ST elevation myocardial infarction.

PMID- 11305998
TI  - Coronary vasoconstriction after coronary angioplasty is attenuated by endothelin
      a receptor antagonism.

PMID- 11305999
TI  - Intravascular ultrasound study in heart transplant recipients at proximal and
      distal branch points.

PMID- 11306000
TI  - Diagnosis and ablation of focal right atrial tachycardia using a new high
      resolution, non-contact mapping system.

PMID- 11306001
TI  - Exercise capacity after repair of Tetralogy of Fallot in infancy.

PMID- 11306002
TI  - Should ascending aortic intramural hematoma be treated surgically?

PMID- 11306003
TI  - Left ventricular function in Nigerian Africans with non-insulin-dependent
      diabetes mellitus.

PMID- 11306004
TI  - Effect of red wine and ethanol on production of nitric oxide in healthy subjects.

PMID- 11306005
TI  - Regulation of sensorimotor gating in rats by hippocampal NMDA: anatomical
      localization.
AB  - Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor
      gating that is reduced in humans with certain neuropsychiatric disorders,
      including schizophrenia, and in rats after manipulations of limbic cortico
      striato-pallido-pontine circuitry. We have reported that PPI is reduced after
      specific manipulations of the hippocampal complex (HPC) in rats, but the
      mechanisms for these effects remain poorly understood. For example, dopaminergic
      substrates clearly regulate PPI, but the PPI-disruptive effects of intra-HPC
      carbachol or NMDA are not reversed by D2 receptor antagonists. This study
      examined the anatomical specificity within the hippocampal complex of the PPI
      disruptive effects of NMDA infusion. Startle magnitude and PPI were assessed
      after acute bilateral infusion of NMDA (0, 0.4 or 0.8 microg) into the dorsal
      subiculum (DS), region CA1, the ventral subiculum (VS), the rostral entorhinal
      cortex (ECr) and the caudal entorhinal cortex (ECc). A dorsal-ventral gradient
      for NMDA effects was observed, with a dose-dependent disruption of PPI after NMDA
      infusion into the VS or EC, but not the DS, and with intermediate level effects
      observed after NMDA infusion into CA1. A second set of studies confirmed that the
      failure of NMDA effects in the DS did not reflect site-related differences in
      startle magnitude or baseline levels of PPI. These findings demonstrate the
      importance of the ventral, but not the dorsal HPC, in the glutamatergic
      regulation of PPI.

PMID- 11306006
TI  - Agonist-induced mu opioid receptor phosphorylation and functional desensitization
      in rat thalamus.
AB  - By metabolically labeling tissue slices from striatum and thalamus with
      [32P]orthophosphoric acid and immunoprecipitating the receptor with mu receptor
      specific antiserum, we found that the endogenous mu receptor in the brain tissue
      did undergo phosphorylation. The phosphorylation occurred at basal level (no drug
      treatment) and was enhanced with DAMGO-treatment. The enhancement of the
      phosphorylation was blocked by naloxone. Morphine stimulation also increased the
      phosphorylation, but the amount of enhancement was less than that caused by DAMGO
      treatment. Mu receptor phosphorylation in the thalamus was much greater than the
      striatum, while no phosphorylation of the mu receptor in the cerebellum was
      detected, even with DAMGO treatment. The extent of mu receptor phosphorylation
      identified in the thalamus, striatum and cerebellum is consistent with the
      previous studies of mu receptor distribution. The time course and dose-response
      studies demonstrated that mu receptor phosphorylation was a rapid event,
      exhibited a positive dose-dependent response, and was similar to that observed in
      the cloned mu receptor in CHO cells. Furthermore, we correlated the change of mu
      receptor phosphorylation with the desensitization of the mu receptor function,
      specifically, inhibition of adenylyl cyclase activity in the thalamus of morphine
      tolerant rats. We found that in the thalamus of rats chronically treated with
      morphine, the enhancement of mu receptor phosphorylation in basal and DAMGO
      treated samples paralleled the desensitization of DAMGO-mediated inhibition of
      adenylyl cyclase. Our results suggest that mu receptor phosphorylation in vivo
      may play an important role in the modulation of mu receptor function following
      both acute exposure to morphine and during the development of morphine tolerance.

PMID- 11306007
TI  - Astrocytic Fos expression in the rat posterior pituitary following LPS
      administration.
AB  - Systemic lipopolysaccharide (LPS) administration has been shown to cause profound
      Fos expression in multiple regions of the brain. In the present experiment, Fos
      expression in the hypothalamic supraoptic nucleus (SON), posterior pituitary, and
      anterior pituitary was investigated using quantitative immunohistochemistry. In
      the SON and anterior pituitary, a large number of Fos-positive cells were
      observed by restraint stress, hyperosmotic administration (1.5, 3, and 9% NaCl),
      and LPS administration (5, 25, and 125 microg/kg). In the posterior pituitary,
      LPS administration caused a significant increase in the number of Fos-positive
      nuclei in a dose-dependent manner, whereas restraint stress and hyperosmotic
      stimulation (1.5 and 3% NaCl) did not increase the number of Fos-positive cells
      and 9% NaCl administration induced weak Fos immunoreactivity. Moreover, a dual
      labeling study using a confocal microscope revealed that Fos-positive cells in
      the posterior pituitary were astrocytes using MAP2, an astrocytic marker in the
      posterior pituitary. Here, we demonstrated that the astrocytes of the posterior
      pituitary expressed Fos in response to LPS administration, which suggests that
      Fos expression participates in the activation of astrocytes during acute-phase
      responses with LPS administration.

PMID- 11306008
TI  - Cyclic AMP-mediated signaling components are upregulated in the prefrontal cortex
      of depressed suicide victims.
AB  - The components of cyclic AMP signaling cascade (catalytic (Calpha) subunit of
      cyclic AMP-dependent protein kinase (PKA) and cyclic AMP response element binding
      protein (CREB)) were quantitated by Western blotting in the prefrontal cortex of
      depressed suicide victims (n=23) and their matched controls (n=14). There was a
      significant increase in the levels of CREB, both in total (tCREB; 121+/-8%
      (mean+/-S.E.M.), P<0.02) and phosphorylated (pCREB; 128+/-9%, P<0.01) forms, but
      not in PKA Calpha levels (109+/-9%, ns), in brains of depressed suicides compared
      to those in control subjects. The increases in CREB were specifically observed in
      antidepressant drug-free subjects (tCREB: 137+/-11%, P<0.01; pCREB: 136+/-12%,
      P<0.02; n=9), but not in the antidepressant-treated subjects (tCREB: 108+/-18%,
      ns; pCREB: 111+/-17%, ns; n=8). There were significant correlations between the
      levels of PKA and those of tCREB and pCREB in the prefrontal cortex of depressed
      suicides. These results indicate that the components of cyclic AMP signaling are
      upregulated in a coordinated manner in brains of depressed suicides and that this
      alteration is not related to antidepressant treatment.

PMID- 11306009
TI  - cFOS and pCREB activation and maternal aggression in mice.
AB  - Lactating mice exhibit a dramatic increase in aggression, termed maternal
      aggression, only in association with the rearing and protection of their
      offspring. Previous work indicates that the neural mechanisms underlying maternal
      and male aggression are different in rodents. In this study, we sought to examine
      possible neural regions involved in the control of maternal aggression by
      combining behavioral testing with immunohistochemistry for both cFOS and pCREB,
      two indirect markers of neuronal activity. All lactating female mice were exposed
      to a male intruder for 20 min and those exhibiting maternal aggression were
      placed in one group and those that were non-aggressive were placed in a second
      group. Thus, the sensory stimuli were similar and the main difference between the
      two groups was the behavior. cFOS expression increased significantly in the
      claustrum, bed nucleus of the stria terminalis, medial preoptic nucleus,
      paraventricular nucleus, medial amygdala, and cortical amygdala in association
      with maternal aggression. In contrast, the number of pCREB-positive cells
      significantly increased only in the ventrolateral portion of the caudal
      periaqueductal gray and in the lateral septum in aggressive lactating mice. Due
      to large variance in the counts of pCREB-positive cells, the data were log
      transformed prior to statistical analysis. Thus, the sites of cFOS and pCREB
      increases do not overlap, but provide complementary indirect information on
      neural regions active during maternal aggression. These results complement
      previous studies of nitric oxide release during maternal aggression to create a
      possible map of the functional neural circuitry underlying maternal aggression.

PMID- 11306010
TI  - Relationships between beta- and alpha2-adrenoceptors and G coupling proteins in
      the human brain: effects of age and suicide.
AB  - Interactions between brain alpha2- and beta-adrenoceptors are of interest in
      physiological (aging) and pathological (major depression) processes involving
      both receptors. In this study, total beta-adrenoceptors and beta1/2-subtypes were
      quantitated in postmortem human brains to investigate their relationships with
      alpha2A-adrenoceptors and specific G proteins during the process of aging and in
      brains of suicide victims. Analysis of [3H]CGP12177 binding, in the presence of
      CGP20712A (beta1-antagonist), indicated that the predominant beta-adrenoceptor in
      the frontal cortex is the beta1-subtype (65-75%). The density of total beta- (r=
      0.60, n=44) or beta1-adrenoceptors (r=-0.78, n=22), but not the beta2-subtype,
      declined with aging (3-80 years). The density of total beta- or beta1
      adrenoceptors, but not the beta2-subtype, correlated with the number of alpha2
      adrenoceptors quantitated in the same brains with the agonist [3H]UK14304 (r=0.71
      0.81) or the antagonist [3H]RX821002 (r=0.61-0.66). Interestingly, the ratios
      alpha2/beta- or alpha2/beta1-adrenoceptors did not correlate with the age of the
      subject at death, indicating that the proportion of alpha2/beta-adrenoceptors in
      brain remains rather constant during the process of aging. The density of beta
      adrenoceptors correlated with the immunodensity of G(alpha)s (r=0.55) and Gbeta
      (r=0.61) proteins, and that of alpha2-adrenoceptors with those of G(alpha)i1/2
      (r=0.88) and Gbeta (r=0.65). In brains of suicides, compared to controls, the
      ratio between alpha2- and beta- or beta1-adrenoceptors (alpha2-full agonist
      sites/beta-sites) was greater (1.3- to 2.0-fold; P<0.05). The results demonstrate
      a close interdependence between brain alpha2- and beta-adrenoceptors during
      aging, and in brains of suicides. The quantitation of the alpha2A/beta
      adrenoceptor ratio could represent a relevant neurochemical index in the study of
      brain pathologies in which both receptors are involved.

PMID- 11306011
TI  - Selective behaviors altered in plasminogen-deficient mice are reconstituted with
      intracerebroventricular injection of plasminogen.
AB  - In vitro studies demonstrate a role for the plasminogen (Plg) system in
      neurological function and recently in vivo studies show a role of the Plg system
      in neurodegeneration after the injection of an excitotoxic agent. Differences in
      the development of neurological function, however, have not been demonstrated in
      the Plg-deficient (Plg-/-) mice compared to wild-type (WT) mice. The role of Plg
      system in neurological function may relate to remodeling which occurs in response
      to various environmental challenges. In this study, behaviors (open field,
      grooming, hind-leg gait, water maze, and acoustic startle reflex) were tested in
      the Plg-deficient and WT mice at 6-8 weeks of age. Grooming, a response to the
      stress of an open field or fur moistening, was increased in the Plg-/--deficient
      mice compared to WT mice, and the acoustic startle reflex (ASR) was markedly
      decreased in the Plg-/- mice. The reduced ASR in Plg-/- mice occurred in mice
      with a mixed C57BL:129 background or in mice with a C57BL background. Plg was
      required for the ASR, since a deficiency of the Plg activators, urokinase (uPA)
      or tissue Plg activator (tPA), did not cause a reduction in the ASR compared to
      their WT control. Infusion of Plg directly into the brain was effective in
      restoring the ASR in the Plg-/- mice, but had no effect on the ASR of WT mice.
      Peripheral bolus injections of Plg or infusion into the jugular vein were
      ineffective in restoring the ASR in the Plg-/- mice. These results indicate that
      Plg is required for the appropriate response to the environmental challenge of a
      sudden loud sound, and that the response can be restored in Plg-/- mice by
      directly infusing Plg into the brain.

PMID- 11306012
TI  - Evidence that oxytocin is an endogenous stimulator of autonomic sympathetic
      preganglionics: the pupillary dilatation response to vaginocervical stimulation
      in the rat.
AB  - Vaginocervical mechanostimulation (VS) was shown previously to release oxytocin
      within the spinal cord and to induce pupillary dilatation. In the present study,
      (a) injection of oxytocin directly to the spinal cord (10 or 25 microg
      intrathecally [i.t.] in 5 microl saline) induced pupillary dilatation when
      observed 1 min after the end of the injection and (b) injection of an oxytocin
      receptor antagonist ([d(CH2)5-Tyr (Me)2-Orn8]-Vasotocin [OTA]; 25 microg i.t. in
      5 microl saline) significantly attenuated the pupillary dilatation response to
      VS, when VS was applied 3 min after the end of the injection. Since activation of
      autonomic sympathetic preganglionic neurons in the thoracic spinal cord produces
      pupillary dilatation, we propose that oxytocin is a central nervous system
      neurotransmitter that stimulates these neurons directly, or perhaps indirectly,
      and thus is a mediator of VS-produced pupillary dilatation.

PMID- 11306013
TI  - Co-administration of adenovirus vector expressing CTLA4-Ig prolongs transgene
      expression in the brain of mice sensitized with adenovirus.
AB  - The duration of transgene expression in the brain is known to be shortened by
      previous sensitization to adenovirus. In order to prolong transgene expression,
      adenovirus vectors expressing CTLA4-Ig (AdCTLA), which blocks the B7-CD28 co
      stimulatory signals required for T-cell activation, were used. Local
      administration of AdCTLA into the brain suppressed both the cellular and humoral
      immune responses to adenovirus vectors, and prolonged the duration of transgene
      expression. AdCTLA may be an effective tool for repeated gene transfer.

PMID- 11306014
TI  - The use-dependent sodium channel blocker mexiletine is neuroprotective against
      global ischemic injury.
AB  - Mechanisms responsible for anoxic/ischemic cell death in mammalian CNS grey and
      white matter involve an increase in intracellular Ca2+, however the routes of
      Ca2+ entry appear to differ. In white matter, pathological Ca2+ influx largely
      occurs as a result of reversal of Na+-Ca2+ exchange, due to increased
      intracellular Na+ and membrane depolarization. Na+ channel blockade has therefore
      been logically and successfully employed to protect white matter from ischemic
      injury. In grey matter ischemia, it has been traditionally presumed that
      activation of agonist (glutamate) operated and voltage dependent Ca2+ channels
      are the primary routes of Ca2+ entry. Less attention has been directed towards
      Na+-Ca2+ exchange and Na+ channel blockade as a protective strategy in grey
      matter. This study investigates mexiletine, a use-dependent sodium channel
      blocker known to provide significant ischemic neuroprotection to white matter, as
      a grey matter protectant. Pentobarbital (65 mg/kg) anesthetized, mechanically
      ventilated Sprague-Dawley rats were treated with mexiletine (80 mg/kg, i.p.).
      Then 25 min later the animals were subjected to 10 min of bilateral carotid
      occlusion plus controlled hypotension to 50 Torr by temporary partial
      exsanguination. Animals were sacrificed with perfusion fixation after 7 days.
      Ischemic and normal neurons were counted in standard H&E sections of hippocampal
      CA1 and the ratio of ischemic to total neurons calculated. Mexiletine pre
      treatment reduced hippocampal damage by approximately half when compared to
      control animals receiving saline alone (45 vs. 88% damage, respectively;
      P<0.001). These results suggest that mexiletine (and perhaps other drugs of this
      class) can provide protection from ischemia to grey matter as well as white
      matter.

PMID- 11306015
TI  - Optical recording of spreading depression in rat neocortical slices.
AB  - A spreading depression (SD) was elicited in adult rat neocortical slices by
      microdrop application of high potassium and the SD propagation pattern was
      analyzed by recording simultaneously the extracellular DC potential and the
      changes in the intrinsic optical signal. The electrical SD with an average peak
      amplitude of 13.2+/-3.4 mV showed a good spatial and temporal correlation with
      the optical signal. In 79% of the slices, the SD was characterized by an initial
      increase of light reflectance by 2.3+/-1.6%, followed by a reflectance decrease
      of 0.5+/-2.4% and finally a larger and long-lasting increase by 5+/-2.4%. In the
      remaining slices, the SD revealed an initial decrease in light reflectance by
      5.8+/-1.8% followed by an increase of 1.4+/-1.2%. In all slices, the recovery in
      the DC recording was faster as in the optical signal. The SD preferentially
      propagated within layers I-IV and could be blocked in most experiments by a
      vertical incision through upper layers or by local glutamate receptor blockade
      following microdrop application of kynurenic acid in layers II-III. The SD could
      be also blocked by bath application of kynurenic acid, MK-801 and octanol, but
      not by the more specific gap junction blocker carbenoxolone. Our results indicate
      that the high density of dendritic processes and glutamate receptors in layers II
      IV promote the horizontal spread of the SD in these cortical layers and that gap
      junctions are not required for the propagation of SD in neocortical slices.

PMID- 11306016
TI  - Lubeluzole inhibits accumulation of extracellular glutamate in the hippocampus
      during transient global cerebral ischemia.
AB  - Increases in extracellular glutamate during cerebral ischemia may play an
      important role in neuronal injury. Lubeluzole is a novel neuroprotective drug,
      which in previous in vitro and focal ischemia studies has been shown to inhibit
      nitric oxide synthesis, to block voltage-gated Na+-ion channels, and to inhibit
      glutamate release. In this study, we investigated the ability of lubeluzole to
      inhibit glutamate accumulation during episodes of transient global cerebral
      ischemia. Twenty-five New Zealand white rabbits were randomized to one of four
      groups: a normothermic control group; a hypothermic group; a 1.25 mg/kg
      lubeluzole group; or a 2.5 mg/kg lubeluzole group. The animals were anesthetized,
      intubated, and ventilated before microdialysis probes were placed in the
      hippocampus. Lubeluzole was given intravenously 90 min before the onset of
      ischemia. Esophageal temperature was maintained at 38 degrees C in the control,
      and lubeluzole treated groups, while the animals in the hypothermia group were
      cooled to 30 degrees C. A 15-min period of global cerebral ischemia was produced
      by inflating a neck tourniquet. Glutamate concentrations in the microdialysate
      were determined using high-performance liquid chromatography (HPLC). During
      ischemia and early reperfusion, glutamate concentrations increased significantly
      in the control group and returned to baseline after 15 min of reperfusion. In the
      lubleuzole 2.5 mg/kg and hypothermia groups, glutamate levels were significantly
      lower (P<0.05) than in the control group and there was no significant change from
      baseline levels during the entire experiment. This study suggests that lubeluzole
      is effective in inhibiting extracellular glutamate accumulation during global
      cerebral ischemia, and has the potential to produce potent neuroprotection when
      instituted prior to an ischemic event.

PMID- 11306017
TI  - Vaginocervical stimulation-induced release of classical neurotransmitters and
      nitric oxide in the nucleus of the solitary tract varies as a function of the
      oestrus cycle.
AB  - The effects of vaginocervical stimulation (VCS) on glutamate (GLU), aspartate
      (ASP), gamma-aminobutyric acid (GABA), noradrenaline (NA), arginine (ARG) and
      nitric oxide (NO) (citrulline) release in the nucleus of the solitary tract (nTS)
      were measured in anaesthetised female rats as a function of the oestrus cycle.
      During pro-oestrus/oestrus (P/E), but not during met-oestrus/di-oestrus (M/D),
      VCS significantly increased concentrations of NA, ASP, GLU, NO (citrulline) and
      GABA, but not ARG. Basal NA concentrations were also increased in P/E. These
      effects were prevented by bilateral section of either the vagus nerve or pelvic
      and hypogastric nerves. Vagotomy also significantly decreased basal NO
      concentrations in M/D and P/E while pelvic and hypogastric nerve section
      significantly increased GABA concentrations. Our results therefore confirm that
      the nTS is a relay structure for the visceral afferents sending information from
      the uterus into the central nervous system. The ability of VCS to trigger
      classical transmitter release and NO in the female is influenced by the stage of
      the oestrous cycle and is routed both via the vagus and pelvic/hypogastric
      nerves.

PMID- 11306018
TI  - Exposure to repeated low-level formaldehyde in rats increases basal
      corticosterone levels and enhances the corticosterone response to subsequent
      formaldehyde.
AB  - Low-level exposure to volatile organic compounds may produce symptoms in humans
      reporting multiple chemical sensitivity (MCS) through altered hypothalamic
      pituitary-adrenal (HPA) axis functioning. We determined whether repeated
      formaldehyde (Form) exposure would alter corticosterone (CORT) levels in a rat
      model of MCS. Male Sprague-Dawley rats were given acute chamber exposures to Air
      or Form (0.7 or 2.4 ppm), and trunk blood was collected 20 or 60 min later. All
      groups showed increased CORT levels above naive basal levels at 20 min and a
      return to baseline by 60 min, with no differences between treatment groups. The
      second experiment examined the effect of repeated Form exposure (1 h/day x 5
      days/week x 2 or 4 weeks) on basal CORT levels and after a final challenge. Basal
      CORT was increased above naive values after 2 week exposure to Air or 0.7 ppm
      Form. By 4 week, CORT levels in the Air group returned to naive values, but
      remained elevated in the 0.7 ppm Form group. There were no differences in basal
      CORT levels among either 2.4 ppm exposed groups. After a final Air or Form
      challenge, the 2 and 4 week Air and 0.7 ppm Form groups had elevated CORT levels
      similar to their acute response, while the 2 and 4 week 2.4 ppm Form groups had
      elevated CORT levels compared to their acute response, indicating enhanced
      reactivity of the HPA axis to subsequent Form. These findings suggest that
      altered HPA axis functioning occurs after repeated low-level Form exposure, and
      may have implications for mechanisms mediating MCS in humans.

PMID- 11306019
TI  - Auditory evoked potentials from auditory cortex, medial geniculate nucleus, and
      inferior colliculus during sleep-wake states and spike-wave discharges in the
      WAG/Rij rat.
AB  - OBJECTIVE: Click auditory evoked potentials (AEP) were simultaneously recorded
      from the auditory cortex (ACx), the medial geniculate nucleus (MGN), and the
      inferior colliculus (IC) in the freely moving WAG/Rij rat, to investigate state
      dependent changes of the AEP in different anatomical locations along the auditory
      pathway. METHODS: AEPs obtained during active (AW) and passive wakefulness (PW),
      slow wave sleep (SWS), rapid-eye-movement sleep (REM) and generalized spike-wave
      discharges (SWD; a specific trait of the WAG/Rij rat, a genetic model for absence
      epilepsy), were compared. RESULTS: The early components in ACx, MGN and IC were
      stable throughout the sleep-wake cycle and SWD, apart from a slight increase in
      the IC during SWD. At all three locations a prominent enlargement of a later
      component (i.e., N32 in IC, N33 in MGN, and N44 in ACx) was found during SWS and
      SWD. CONCLUSIONS: The early AEP components are not modulated by the normal sleep
      wake states, and are not impaired during SWD. A strong state-dependent modulation
      of a later AEP component occurs at all three anatomical locations investigated.
      This suggests that apart from the thalamic burst firing mode, additional
      mechanisms must exist for the enlargement of the AEP during EEG-synchronized
      states at the prethalamic and cortical level.

PMID- 11306020
TI  - Increase in antidromic excitability in presumed serotonergic dorsal raphe neurons
      during paradoxical sleep in the cat.
AB  - Putative serotonergic dorsal raphe (DRN) neurons display a dramatic state-related
      change in behaviour, discharging regularly at a high rate during waking and at
      progressively slower rates during slow-wave sleep (SWS) and ceasing firing during
      paradoxical sleep (PS). Using the antidromic latency technique and extracellular
      recording, we have examined the change in neuronal excitability of presumed
      serotonergic DRN neurons during the wake-sleep cycle in freely moving cats. We
      found that, under normal conditions, suprathreshold stimulation of the main
      ascending serotonergic pathway resulted in a marked decrease in both the
      magnitude and variability of antidromic latency during PS, while subthreshold
      stimulation led to a marked increase in antidromic responsiveness during PS
      compared with during other behavioural states. The antidromic latency shift
      resulted from a change in the delay between the initial segment (IS) and soma
      dendritic (SD) spikes, the antidromic latency being inversely related to the
      interval between the stimulus and the preceding spontaneous action potential. A
      marked decrease in the magnitude and variability of antidromic latency was also
      seen following suppression of the spontaneous discharge of DRN neurons by
      application of 5-HT autoreceptor agonists or muscimol, a potent GABA agonist. A
      marked IS-SD delay or blockage of SD spikes was, however, seen in association
      with the PS occurring during recovery from 5-HT autoreceptor agonist or during
      muscimol application. The present findings are discussed in the light of previous
      in vitro intracellular recording data and our recent findings of the
      disfacilitation mechanisms responsible for the cessation of discharge of DRN
      neurons during PS.

PMID- 11306021
TI  - Lesion and electrical stimulation of the ventral tegmental area modify persistent
      nociceptive behavior in the rat.
AB  - The ventral tegmental area (VTA) has been traditionally related with the control
      of motor responses. However, some studies show that this area is also involved in
      the processing of nociceptive information. It has been reported that this nucleus
      participates in the dissociative analgesia phenomenon. In the few works where
      electrical stimulation and lesion of the VTA have been performed, evaluated with
      persistent or chronic pain related behaviors, contradictory results have been
      obtained. Thus, a more detailed analysis of the role of the VTA in persistent
      pain is needed. Two series of experiments were performed: lesions of this nucleus
      were done with radiofrequency, (bilaterally at two points per side using a
      temperature range from 50 to 80 degrees C), and the VTA was electrically
      stimulated (10 min daily over 5 days, 2 ms rectangular pulses at 100 Hz during 1
      s every 5 s) using two different schemes:10 min before the induction of the
      nociceptive stimulus and 90 min after the induction of the nociceptive stimulus.
      The latter allowed us to distinguish if the VTA electrical stimulation had a
      distinctive antinociceptive effect when applied before or after the induction of
      the nociceptive stimulus on a persistent pain related behavioral response in the
      rat, the self injury behavior (SIB). Our results showed that VTA lesions enhanced
      the occurrence of SIB; while activation of this same nucleus by electrical
      stimulation after the nociceptive stimulus, but not before, facilitates the
      analgesic process, expressed as a 1 day delay in SIB onset. These results
      indicate that the VTA is a brain structure that plays a key role in the
      processing and modulation of persistent pain information. Data are discussed in
      terms of the relationship of the VTA with the affective component of pain.

PMID- 11306022
TI  - Activated caspase-3 expression in Alzheimer's and aged control brain: correlation
      with Alzheimer pathology.
AB  - Several studies have suggested that activated caspase-3 has properties of a cell
      death executioner protease. In this study, we examined the expression of
      activated caspase-3 in AD and aged control brains. Activated caspase-3
      immunoreactivity was seen in neurons, astrocytes, and blood vessels, was elevated
      in AD, and exhibited a high degree of colocalization with neurofibrillary tangles
      and senile plaques. These data suggest that activated caspase-3 may be a factor
      in functional decline and may have an important role in neuronal cell death and
      plaque formation in AD brain.

PMID- 11306023
TI  - Acoustic priming lowers the threshold for electrically induced seizures in mice
      inferior colliculus, but not in the deep layers of superior colliculus.
AB  - Mice become highly susceptible to audiogenic seizures (AGS) after exposing them
      to an intense noise in their early life (priming). To elucidate the brain
      mechanisms for this priming effect of AGS, we compared the threshold current
      intensities inducing AGS syndromes between primed (n=88) and non-primed (n=84)
      mice by electrically stimulating the central nucleus and external cortex of the
      inferior colliculus (CIC and ECIC), and the deep layers of the superior
      colliculus (DLSC). The threshold for wild running was significantly lower for the
      primed mice than for the control mice in the case of the CIC and ECIC, but not
      the DLSC. The current intensity for inducing clonic seizure was lower for the
      primed mice than for the control mice in the case of the ECIC. These results show
      that the inferior colliculus (IC) plays an important role in the priming effect
      of AGS in mice, but that the DLSC does not.

PMID- 11306024
TI  - Expression of connexin 30 in the developing mouse cochlea.
AB  - Mutations in the GJB6 gene encoding connexin 30 (Cx30) can cause dominant forms
      of nonsyndromic deafness. By studying immunohistochemical localization of Cx30 in
      the mouse cochlea at different ages from 0 to 30 days after birth, we found that
      the expression of Cx30 is nearly the same as that of Cx26. These findings suggest
      that as well as Cx26, Cx30 may also contribute to the generation and maturation
      of endocochlear potential.

PMID- 11306026
TI  - Order and disorder in mitochondrial aldehyde dehydrogenase.
AB  - One of the most notable and currently unexplained features of the mitochondrial
      form of aldehyde dehydrogenase is its property of half-of-the-sites reactivity.
      An appropriate description of this phenomenon can be to consider this as the
      extreme example of negative cooperativity. This implies, therefore, that a
      pathway of communication must exist between active sites in order to convey the
      structural consequences of ligand binding. Data from four different structures of
      human ALDH2 collected during the past 2 years may shed some light on one possible
      pathway for the propagation of structural information. We recently published a
      2.6 A structure of a binary complex between ALDH2 and NAD(+) in which the
      predominant conformation of the cofactor differed between different subunits in
      the structure. We now have three unpublished structures, a wild-type apo-enzyme
      structure at 2.25 A resolution, a wild-type structure complexed with NADH at 2.45
      A resolution, and a site-directed mutant of ALDH2 where Arg475 is mutated to Gln,
      as an apo-enzyme to 2.75 A resolution. A detailed comparison of their structures
      reveals that a disorder-to-order transition occurs upon coenzyme binding in the
      area immediately surrounding the adenosine-binding site (residues 224-233 and 246
      262). These residues correspond to the two helices that surround the adenine ring
      of the cofactor. Since the helix comprised of residues 246-262 contacts its dimer
      related helix across the subunit interface, this could induce as of yet
      unidentified subtle changes in structure that impair productive binding of the
      cofactor in the second subunit. The unique characteristics and three-dimensional
      structure of the R475Q variant of ALDH2 supports a role in subunit communication
      for these residues. This mutated enzyme displays positive cooperativity for
      cofactor binding. The structure of the apo-enzyme shows that the average thermal
      parameters for the residues involved in adenosine binding are drastically
      elevated as is a stretch of amino acids surrounding the site of mutation
      (residues 471-480). We hypothesize that cofactor binding displays a Hill
      coefficient of approximately 2 because binding of coenzyme to one subunit in a
      dimer orders the residues responsible for cofactor binding in the second, thus
      promoting binding. The difference between these alterations being positively
      versus negatively cooperative is likely related to the magnitude of the
      structural changes. Further work is in progress to confirm this hypothesis as it
      may shed light on the dominant effects of the E487K allelic variant, since Glu487
      interacts with Arg475.

PMID- 11306027
TI  - Chemical mechanism and substrate binding sites of NADP-dependent aldehyde
      dehydrogenase from Streptococcus mutans.
AB  - Non-phosphorylating glyceraldehyde 3-phosphate dehydrogenase from Streptococcus
      mutans (GAPN) belongs to the aldehyde dehydrogenase (ALDH) family, which
      catalyzes the irreversible oxidation of a wide variety of aldehydes into acidic
      compounds via a two-step mechanism: first, the acylation step involves the
      formation of a covalent ternary complex ALDH-cofactor-substrate, followed by the
      oxidoreduction process which yields a thioacyl intermediate and reduced cofactor
      and second, the rate-limiting deacylation step. Structural and molecular factors
      involved in the chemical mechanism of GAPN have recently been examined.
      Specifically, evidence was put forward for the chemical activation of catalytic
      Cys-302 upon cofactor binding to the enzyme, through a local conformational
      rearrangement involving the cofactor and Glu-268. In addition, the invariant
      residue Glu-268 was shown to play an essential role in the activation of the
      water molecule in the deacylation step. For E268A/Q mutant GAPNs, nucleophilic
      compounds like hydrazine and hydroxylamine were shown to bind and act as
      substrates in this step. Further studies were focused at understanding the
      factors responsible for the stabilization and chemical activation of the covalent
      intermediates, using X-ray crystallography, site-directed mutagenesis, kinetic
      and physico-chemical approaches. The results support the involvement of an
      oxyanion site including the side-chain of Asn-169. Finally, given the strict
      substrate-specificity of GAPN compared to other ALDHs with wide substrate
      specificity, one has also initiated the characterization of the G3P binding
      properties of GAPN. These results will be presented and discussed from the point
      of view of the evolution of the catalytic mechanisms of ALDH.

PMID- 11306028
TI  - Differences in nucleotide specificity and catalytic mechanism between Vibrio
      harveyi aldehyde dehydrogenase and other members of the aldehyde dehydrogenase
      superfamily.
AB  - The fatty aldehyde dehydrogenase (Vh-ALDH) isolated from the luminescent
      bacterium, Vibrio harveyi, differs from other aldehyde dehydrogenases in its high
      affinity for NADP(+). The binding of NADP(+) appears to arise from the
      interaction of the 2'-phosphate of the adenosine moiety of NADP(+) with a
      threonine (T175) in the nucleotide recognition site just after the beta(B) strand
      as well as with an arginine (R210) that pi stacks over the adenosine moiety. The
      active site of Vh-ALDH contains the usual suspects of a cysteine (C289), two
      glutamates (E253 and E377) and an asparagine (N147) involved in the aldehyde
      dehydrogenase mechanism. However, Vh-ALDH has one polar residue in the active
      site that distinguishes it from other ALDHs; a histidine (H450) is in close
      contact with the cysteine nucleophile. As a glutamate has been implicated in
      promoting the nucleophilicity of the active site cysteine residue in ALDHs, the
      close contact of a histidine with the cysteine nucleophile in Vh-ALDH raises the
      possibility of alternate routes to increase the reactivity of the cysteine
      nucleophile. The effects of mutation of these residues on the different functions
      catalyzed by Vh-ALDH including acylation, (thio)esterase, reductase and
      dehydrogenase activities should help define the specific roles of the residues in
      the active site of ALDHs.

PMID- 11306029
TI  - Beyond the catalytic core of ALDH: a web of important residues begins to emerge.
AB  - Site-directed mutagenesis was performed in class 3 aldehyde dehydrogenase (ALDH)
      on both strictly conserved, non-glycine residues, Glu-333 and Phe-335. Both lie
      in Motif 8 and are indicated to be of central catalytic importance from their
      positions in the tertiary structure. In addition, a highly conserved residue at
      the end of Motif 8, Pro-337, and Asp-247, which interacts with the main chain of
      Motif 8, were also mutated. All substitutions were conservative. Kinetic values
      clearly show that Glu-333 and Phe-335 are crucial to efficient catalysis, along
      with Asp-247. Pro-337 appears to have a different role, most likely relating to
      folding.

PMID- 11306030
TI  - Subunit communication in tetrameric class 2 human liver aldehyde dehydrogenase as
      the basis for half-of-the-site reactivity and the dominance of the oriental
      subunit in a heterotetramer.
AB  - Data has been published showing that in heterotetrameric liver mitochondrial
      aldehyde dehydrogenase composed of the active (E487) and the inactive Oriental
      variant (K487) subunit, the Oriental variant was dominant and caused the
      inactivation of the E487 subunit. The published structures of the enzyme showed
      that the glutamate at position 487 is salt bonded to an arginine (475) in a
      different subunit. Arg475 was mutated to a glutamine to test for its importance
      in causing the Oriental variant to be an enzyme with a high Km for NAD and a low
      specific activity. Unexpectedly, the R475Q mutant exhibited positive
      cooperativity in NAD binding with a Hill coefficient of 2. Individual
      heterotetramers composed of subunits of E487 and K487 were produced by making
      changes to two residues on the surface of the enzyme and then co-expressing both
      cDNAs in E. coli. The E(3)K form had essentially 50% the activity of the E(4)
      homotetrameric form while EK(3) had essentially the same properties as did the
      homotetrameric K(4) Oriental variant. This showed that in a dimer pair composed
      of one K- and one E- subunit the K-subunit became dominant and caused the
      inactivation of its E-partner. Further, pre-steady state burst data and steady
      state kinetic data make it appear that there was one functioning active subunit
      in each of the dimer pairs that made up the tetrameric enzyme. Thus, the half-of
      the-site reactivity is a result of having one functioning and one non-functioning
      subunit in each dimer pair. The actual structural basis for this is still not
      understood, but could be related to the E487-R475 inter-dimer salt bond.

PMID- 11306031
TI  - Interaction of sheep liver cytosolic aldehyde dehydrogenase with quercetin,
      resveratrol and diethylstilbestrol.
AB  - The effects of quercetin and resveratrol (substances found in red wine) on the
      activity of cytosolic aldehyde dehydrogenase in vitro are compared with those of
      the synthetic hormone diethylstilbestrol. It is proposed that quercetin inhibits
      the enzyme by binding competitively in both the aldehyde substrate binding-pocket
      and the NAD(+)-binding site, whereas resveratrol and diethylstilbestrol can only
      bind in the aldehyde site. When inhibition is overcome by high aldehyde and
      NAD(+) concentrations (1 mM of each), the modifiers enhance the activity of the
      enzyme; we hypothesise that this occurs through binding to the enzyme-NADH
      complex and consequent acceleration of the rate of dissociation of NADH. The
      proposed ability of quercetin to bind in both enzyme sites is supported by gel
      filtration experiments with and without NAD(+), by studies of the esterase
      activity of the enzyme, and by modelling the quercetin molecule into the known
      three-dimensional structure of the enzyme. The possibility that interaction
      between aldehyde dehydrogenase and quercetin may be of physiological significance
      is discussed.

PMID- 11306032
TI  - Complexes of NADH with betaine aldehyde dehydrogenase from leaves of the plant
      Amaranthus hypochondriacus L.
AB  - The kinetic mechanism of betaine aldehyde dehydrogenase from leaves of the plant
      Amaranthus hypochondriacus is ordered with NAD(+) adding first. NADH is a
      noncompetitive inhibitor against NAD(+), which was interpreted before as evidence
      of an iso mechanism, in which NAD(+) and NADH binds to different forms of free
      enzyme. With the aim of testing the proposed kinetic mechanism, we have now
      investigated the ability of NADH to form different complexes with the enzyme. By
      initial velocity and equilibrium binding studies, we found that the steady-state
      levels of E.glycine betaine are negligible, ruling out binding of NADH to this
      complex. However, NADH readily bind to E.betaine aldehyde, whose levels most
      likely are kinetically significant given its low dissociation constant. Also,
      NADH combined with E.NADH and E.NAD(+). Finally, NADH was not able to revert the
      hydride transfer step, what suggest that there is no acyl-enzyme intermediate,
      i.e. the release of the reduced dinucleotide takes place after the deacylation
      step. Although formation of the complex E.NAD(+).NADH would produce an
      uncompetitive effect in the inhibition of NADH against NAD(+), the iso mechanism
      cannot be conclusively discarded.

PMID- 11306033
TI  - Overview--in vitro inhibition of aldehyde dehydrogenase by disulfiram and
      metabolites.
AB  - Disulfiram (DSF) has found extensive use in the aversion therapy treatment of
      recovering alcoholics. It is known that DSF or a metabolite irreversibly inhibits
      aldehyde dehydrogenase (ALDH). However, the actual mechanism of inhibition is
      still not known. In this work we describe the in vitro interactions of DSF, as
      well as a principal metabolite S-methyl-N,N-diethylthiocarbamoyl sulfoxide (MeDTC
      SO), with both recombinant rat liver mitochondrial monomeric ALDH (rmALDH) and
      homotetrameric rmALDH. We show that DSF directly inhibits rmALDH (IC(50)=36.4
      microM) by inducing the formation of an intramolecular disulfide bond. We also
      demonstrate by HPLC-MS analysis of a Glu-C digest of DSF-treated rmALDH that the
      intramolecular disulfide bridge formed involves two of the three cysteines
      located at the active site of the enzyme. Using a combination of HPLC-MS and HPLC
      MS/MS, we further show that the electrophilic metabolite MeDTC-SO also inhibits
      rmALDH (IC(50)=4.62 microM). We isolate and identify a carbamoylated peptide at
      Cys(302) with the sequence FNQGQC(301)C(302)C(303). Hence we show that MeDTC-SO
      exhibits its inhibitory effect by covalently modifying the -SH side-chain of
      Cys(302), present at the active site rmALDH. Finally we show using SEC-MS that
      both DSF and MeDTC-SO do not prevent formation of the homotetramer of rmALDH, but
      inhibit the enzyme by acting directly at the active site of specific monomers of
      rmALDH.

PMID- 11306034
TI  - In vivo inhibition of aldehyde dehydrogenase by disulfiram.
AB  - Disulfiram (DSF) has found extensive use in the aversion therapy treatment of
      recovering alcoholics. Although it is known to irreversibly inhibit hepatic
      aldehyde dehydrogenase (ALDH), the specific mechanism of in vivo inhibition of
      the enzyme by the drug has not yet been determined. In this report, we
      demonstrate a novel, but simple and rapid method for structurally characterizing
      in vivo derived protein-drug adducts by linking on-line sample processing to HPLC
      electrospray ionization mass spectrometry (HPLC-MS) and HPLC-tandem mass
      spectrometry (HPLC-MS/MS). Employing this approach, rats were administered DSF,
      and their liver mitochondria were isolated and solubilized. Both native and in
      vivo DSF-treated mitochondrial ALDH (rmALDH) were purified in one-step with an
      affinity cartridge. The in vivo DSF-treated rmALDH showed 77% inhibition in
      enzyme activity as compared to that of the control. Subsequently, the control and
      DSF-inhibited rmALDH were both subjected to HPLC-MS analyses. We were able to
      detect two adducts on DSF-inhibited rmALDH as indicated by the mass increases of
      approximately 71 and approximately 100 Da. To unequivocally determine the site
      and structure of these adducts, on-line pepsin digestion-HPLC-MS and HPLC-MS/MS
      were performed. We observed two new peptides at MH(+)=973.7 and 1001.8 in the
      pepsin digestion of DSF-inhibited enzyme. These two peptides were subsequently
      subjected to HPLC-MS/MS for sequence determination. Both peptides possessed the
      sequence FNQGQC(301)C(302)C(303), derived from the enzyme active site region, and
      were modified at Cys(302) by N-ethylcarbamoyl (+71 Da) and N-diethylcarbamoyl
      (+99 Da) adducts. These findings indicated that N-dealkylation may be an
      important step in DSF metabolism, and that the inhibition of ALDH occurred by
      carbamoylation caused by one of the DSF metabolites, most likely S-methyl-N,N
      diethylthiocarbamoyl sulfoxide (MeDTC-SO).

PMID- 11306035
TI  - Catalysis of dehydrogenation of 4-trans-(N,N-dimethylamino)cinnamaldehyde by
      aldehyde dehydrogenase.
AB  - 4-trans-(N,N-dimethylamino)cinnamaldehyde (DACA) is a chromophoric and
      fluorogenic substrate of aldehyde dehydrogenase. Fluorescence of DACA is enhanced
      by binding to aldehyde dehydrogenase in the absence of catalysis both in the
      presence and absence of the coenzyme analogue 5'AMP. DACA binds to aldehyde
      dehydrogenase with a dissociation constant of 1-3 microM and stoichiometry of 2
      mol mol(-1) enzyme. Incorporation of DACA during catalysis was also investigated
      and found to be 2 mol DACA mol(-1) enzyme. Effect of pH on the stoichiometry of
      DACA incorporation during catalysis has shown that DACA incorporation remained
      constant at 2 mol DACA mol(-1) enzyme, despite a 74-fold velocity enhancement
      between pH 5.0 and 9.0. Increase of pH increased decomposition of enzyme-acyl
      intermediate without affecting the rate-limiting step of the reaction. At pH 7.0
      the pH stimulated velocity enhancement was 10-fold over that at pH 5.0; further
      velocity enhancement (11.5-fold that of pH 7.0) was achieved by 150 microM Mg(2+)
      ions. The velocity at pH 7.0 with Mg(2+) exceeded that of pH 9.0, and that at
      maximal pH stimulation at pH 9.5. It was observed that level of intermediate
      decreased to about 1 mol mol(-1) enzyme, indicating that Mg(2+) ions increased
      the rate of decomposition of the enzyme-acyl intermediate and shifted the rate
      limiting step of the reaction to another step in the reaction sequence.

PMID- 11306036
TI  - Coenzyme specificity in aldehyde dehydrogenase.
AB  - Influences on coenzyme preference are explored. Lysine 137 (192 in class 1/2
      ALDH) lies close to the adenine ribose, directly interacting with the adenine
      ribose in NAD-specific ALDHs and the 2'-phosphate of NADP in NADP-specific ALDHs.
      Lys-137 in class 3 ALDH interacts with the adenine ribose indirectly through an
      intervening water molecule. However, this residue is present in all ALDHs and, as
      a result, is unlikely to directly influence coenzyme specificity. Glutamate 140
      (195) coordinates the 2'- and 3'-hydroxyls of the adenine ribose of NAD in the
      class 3 tertiary structure. Thus, it appeared that this residue would influence
      coenzyme specificity. Mutation to aspartate, asparagine, glutamine or threonine
      shifts the coenzyme specificity towards NADP, but did not completely change the
      specificity. Still, the mutants show the 2'-phosphate of NADP is repelled by Glu
      140 (195). Although Glu-140 (195) has a major influence on coenzyme specificity,
      it is not the only influence since class 3 ALDHs, can use both coenzymes, and
      class 2 ALDHs, which are NAD-specific, have a glutamate at this position. One
      explanation may be that the larger space between Lys-137 (192) and the adenine
      ribose hydroxyls in the class 3 ALDH:NAD binary structure may provide space to
      accommodate the 2'-phosphate of NADP. Also, a structural shift upon binding NADP
      may also occur in class 3 ALDHs to help accommodate the 2'-phosphate of NADP.

PMID- 11306037
TI  - Interaction of human aldehyde dehydrogenase with aromatic substrates and ligands.
AB  - The substrate benzaldehyde (but not propionaldehyde) could elute aldehyde
      dehydrogenase from a p-hydroxyacetophenone-affinity column, and inhibit the
      esterase activity (K(i)=47 microM), indicating that this simple aromatic aldehyde
      binds to the free enzyme and possibly in the substrate-binding site. Thus, the
      kinetic mechanism for aldehyde dehydrogenase might be dependent upon which
      aldehyde is used in the reaction. Chloramphenicol which also elutes the enzyme
      from the affinity column, shows a discriminatory effect by inhibiting the ALDH1
      oxidation of benzaldehyde and activating that of propionaldehyde while showing no
      effect when assayed with hexanal or cyclohexane-carboxaldehyde. Chloramphenicol
      is an uncompetitive inhibitor against NAD when benzaldehyde is the substrate. We
      propose that this drug might interact with both the benzaldehyde and NAD binding
      sites.

PMID- 11306038
TI  - Inhibition of ALDH3A1-catalyzed oxidation by chlorpropamide analogues.
AB  - In our efforts to identify agents that would specifically inhibit ALDH3A1, we had
      previously studied extensively the effect of an N(1)-alkyl, an N(1)-methoxy, and
      several N(1)-hydroxy-substituted ester derivatives of chlorpropamide on the
      catalytic activities of ALDH3A1s derived from human normal stomach mucosa
      (nALDH3A1) and human tumor cells (tALDH3A1), and of two recombinant aldehyde
      dehydrogenases, viz. human rALDH1A1 and rALDH2. The N(1)-methoxy analogue of
      chlorpropamide, viz. 4-chloro-N-methoxy-N
      [(propylamino)carbonyl]benzenesulfonamide (API-2), was found to be a relatively
      selective and potent inhibitor of tALDH3A1-catalyzed oxidation as compared to its
      ability to inhibit nALDH3A-catalyzed oxidation, but even more potently inhibited
      ALDH2-catalyzed oxidation, whereas an ester analogue, viz. (acetyloxy)[(4
      chlorophenyl)sulfonyl]carbamic acid 1,1-dimethylethyl ester (NPI-2), selectively
      inhibited tALDH3A1-catalyzed oxidation as compared to its ability to inhibit
      nALDH3A1-, ALDH1A1- and ALDH2-catalyzed oxidations, and this inhibition was
      apparently irreversible. Three additional chlorpropamide analogues, viz. 4-chloro
      N,O-bis(ethoxycarbonyl)-N-hydroxybenzenesulfonamide (NPI-4), N,O
      bis(carbomethoxy)methanesulfohydroxamic acid (NPI-5), and 2-[(ethoxycarbonyl)oxy]
      1,2-benzisothiazol-3(2H)-one 1,1-dioxide (NPI-6), were evaluated in the present
      investigation. Quantified were NAD-linked oxidation of benzaldehyde catalyzed by
      nALDH3A1 and tALDH3A1, and NAD-linked oxidation of acetaldehyde catalyzed by
      rALDH1A1 and rALDH2, all at 37 degrees C and pH 8.1, and in the presence and
      absence of inhibitor. NPI-4, NPI-5 and NPI-6 were not substrates for the
      oxidative reactions catalyzed by any of the ALDHs studied. Oxidative reactions
      catalyzed by the ALDH3A1s, rALDH1A1 and rALDH2 were each inhibited by NPI-4 and
      NPI-5. NPI-6 was a poor inhibitor of nALDH3A1- and tALDH3A1-catalyzed oxidations,
      but was a relatively potent inhibitor of rALDH1A1- and rALDH2-catalyzed
      oxidations. In all cases, inhibition of ALDH-catalyzed oxidation was directly
      related to the product of inhibitor concentration and preincubation
      (enzyme+inhibitor) time. As judged by the product values (microMxmin) required to
      effect 50% inhibition (IC(50)): (1) nALDH3A1 and tALDH3A1 were essentially
      equisensitive to inhibition by NPI-4 and NPI-5, and both enzymes were poorly
      inhibited by NPI-6; (2) rALDH1A1 was, relative to the ALDH3A1s, slightly more
      sensitive to inhibition by NPI-4 and NPI-5, and far more sensitive to inhibition
      by NPI-6; and (3) rALDH1A1 was, relative to rALDH2, essentially equisensitive to
      inhibition by NPI-5, whereas, it was slightly more sensitive to inhibition by NPI
      4 and NPI-6.

PMID- 11306039
TI  - Role of the C-terminal tail on the quaternary structure of aldehyde
      dehydrogenases.
AB  - To assess the importance of the C-terminal tail in the structure of aldehyde
      dehydrogenases (ALDH), mutants of tetrameric ALDH1 were generated by adding a
      tail of 5 amino acids (ALDH1-5aa) or the tail from the class 3 enzyme. A mutant
      of dimeric ALDH3 was made, where 17 amino acids from the C-terminus were deleted
      to generate ALDH3DeltaTail. The expression and solubility of the ALDH1 mutants
      was slightly lower than the wild type. Expression of ALDH3DeltaTail mutant was
      similar to wild type, but the solubility was only about 30%. The activity of
      ALDH1-5aa mutant was 30%, while ALDH1-H3Tail mutant was 60% active, compared to
      the wild type. The activity of the class 3 mutant was similar to the activity of
      the parent ALDH3 enzyme. Analysis of stability against temperature demonstrated
      that ALDH1-5aa was more stable than ALDH1 wild type, while the ALDH1-H3Tail
      mutant was considerably less stable than ALDH1, showing a stability similar to
      ALDH3. However, native gel and size exclusion analysis, showed no changes in the
      oligomerization state of these mutants. ALDH3DeltaTail mutant was more stable
      than wild type; the stability against temperature was similar to ALDH1. The
      ALDH3DeltaTail mutant showed an elution similar to that of ALDH1 from the size
      exclusion column, indicating that it was possibly a tetramer. These results show
      that the tail in ALDH3, is involved in the determination of the quaternary
      structure of ALDH3, but has no effect on the ALDH1 enzyme; the absence of the C
      terminal tail is not the only factor participating in holding the dimers
      together. Thus, the interaction between single residues, or interactions with the
      N-terminal region might be more important for maintaining stable tetramers.

PMID- 11306040
TI  - Purification and characterization of grass carp mitochondrial aldehyde
      dehydrogenase.
AB  - The molecular biology and enzymology of aldehyde dehydrogenase (ALDH) have been
      extensively investigated. However, most of the studies have been confined to the
      mammalian forms, while the sub-mammalian vertebrate ALDHs are relatively
      unexplored. In the present investigation, an ALDH was purified from the
      hepatopancreas of grass carp (Ctenopharygodon idellus) by affinity
      chromatographies on alpha-cyanocinnamate-Sepharose and Affi-gel Blue agarose. The
      800-fold purified enzyme had a specific activity of 4.46 U/mg toward the
      oxidation of acetaldehyde at pH 9.5. It had a subunit molecular weight of 55000.
      Isoelectric focusing showed a single band with a pI of 5.3. N-terminal amino acid
      sequencing of 30 residues revealed a positional identity of approximately 70%
      with mammalian mitochondrial ALDH2. The kinetic properties of grass carp ALDH
      resembled those of mammalian ALDH2. The optimal pH for the oxidation of
      acetaldehyde was 9.5. The K(m) values for acetaldehyde were 0.36 and 0.31 microM
      at pH 7.5 and 9.5, respectively. Grass carp ALDH also possessed esterase activity
      which could be activated in the presence of NAD(+).

PMID- 11306041
TI  - Making an Oriental equivalent of the yeast cytosolic aldehyde dehydrogenase as
      well as making one with positive cooperativity in coenzyme binding by mutations
      of glutamate 492 and arginine 480.
AB  - Yeast has at least three partially characterized aldehyde dehydrogenases.
      Previous studies by gene disrupted in our laboratory revealed that the
      Saccharomyces cerevisiae cytosol ALDH1 played an important role in ethanol
      metabolism as did the class 2 mitochondrial enzyme. To date, few mutagenesis
      studies have been performed with the yeast enzymes. An important human variant of
      ALDH is one found in Asian People. In it, the glutamate at position 487 is
      replaced by a lysine. This glutamate interacts with an arginine (475) that is
      located in the subunit that makes up the dimer pair in the tetrameric enzyme.
      Sequence alignment shows that these two residues are located at positions 492 and
      480, respectively, in the yeast class 1 enzyme which shares just 45% sequence
      identity with the human enzymes. Mutating glutamate 492 to lysine produced an
      enzyme with altered kinetic properties when compared to the wild-type glutamate
      enzyme. The K(m) for NADP of E492K increased to nearly 3600 microM compare to 40
      microM for wild-type enzyme. The specific activity decreased more than 10-fold
      with respect to the recombinant wild-type yeast enzyme. Moreover, substituting a
      glutamine for a glutamate was not detrimental in that the E492Q had wild-type
      like K(m) for NADP and V(max). These properties were similar to the changes found
      with the human class 2 E487K mutant form. Further, mutating arginine 480 to
      glutamine produced an enzyme that exhibited positive cooperativity in NADP
      binding. The K(m) for NADP increased 11-fold with a Hill coefficient of 1.6. The
      NADP-dependent activity of R480Q mutant was 60% of wild-type enzyme. Again, these
      results are very similar to what we recently showed to occur with the human
      enzyme [Biochemistry 39 (2000) 5295-5302]. These findings show that the even
      though the glutamate and arginine residues are not conserved, similar changes
      occur in both the human and the yeast enzyme when either is mutated.

PMID- 11306042
TI  - Corneal and stomach expression of aldehyde dehydrogenases: from fish to mammals.
AB  - We have studied the distribution of the ALDH3A1, ALDH1A1 and ALDH2 proteins in
      the cornea and stomach of several animal species, including mammals (C57BL/6J and
      SWR/J mice, rat and pig), birds (chicken and turkey), amphibians (frog) and fish
      (trout and zebrafish). High ALDH3A1 protein levels and catalytic activities were
      detected in C57BL/6J mouse, rat and pig. We found complete absence of the ALDH3A1
      protein in SWR/J mice, which carry the Aldh3a1(c) allele characterized by four
      amino acid substitutions (G88R, I154N, H305R and I352V) and lack of enzymatic
      activity. This indicates that the SWR/J mouse strain is a natural gene knockout
      model for ALDH3A1. Traces of ALDH3A1 were detected in rabbit, whereas expression
      was absent from chicken, turkey, frog, trout, and zebrafish. Interestingly,
      significant levels of the cytosolic ALDH1A1 and mitochondrial ALDH2 proteins were
      detected by immunoblot analysis in all examined species that are deficient in
      ALDH3A1 expression. In contrast, no ALDH1A1 or ALDH2 protein was detected in the
      species expressing ALDH3A1. It can, therefore, be concluded that corneal
      expression of ALDH3A1 or ALDH1A1/ALDH2 occurs in a taxon-specific manner,
      supporting the protective role of these ALDHs in cornea against the UV-induced
      oxidative damage.

PMID- 11306043
TI  - Betaine aldehyde dehydrogenase from rat liver mitochondrial matrix.
AB  - An NAD-linked aldehyde dehydrogenase which in addition to aliphatic and aromatic
      aldehydes, metabolizes aminoaldehydes and betaine aldehyde, has been purified to
      homogeneity from male Sprague-Dawley rat liver mitochondria. The properties of
      the rat mitochondrial enzyme are similar to those of a rat liver cytoplasmic
      betaine aldehyde dehydrognase and the human cytoplasmic E3 isozyme. The primary
      structure. of four tryptic peptides were also similar; only one difference in
      primary structure was observed. The close similarity of properties of the
      cytoplasmic with the mitochondrial form suggest that the cytoplasmic and
      mitochondrial betaine aldehyde dehydrogenase may be coded for by the same nuclear
      gene. Investigation of the mitochondrial form by isoelectric focusing resulted in
      visualization of multiple forms, different from those seen in the cytoplasm
      suggesting that the enzyme may be processed in the mitochondria.

PMID- 11306044
TI  - Molecular dynamics simulation of class 3 aldehyde dehydrogenase.
AB  - Molecular dynamics (MD) simulation of the rat class 3 aldehyde dehydrogenase
      (ALDH) with nicotinamide dinucleotide (NAD) cofactors and explicit water
      molecules are reported. Our results demonstrate that MD simulation using the
      latest methodologies can maintain the crystal structure of the enzyme, as well as
      closely reproduce the short timescale dynamics of the enzyme. Furthermore, the
      examination of the distance between the nucleophilic Cys-243 and the NAD cofactor
      reveal important fluctuations that could be linked to ALDH catalysis. Finally,
      our quantum mechanical model of benzaldehyde in the active site of ALDH
      demonstrates that the enzyme requires only minor conformational changes to be
      poised for nucleophilic attack on the substrate.

PMID- 11306045
TI  - The effect of a novel irreversible inhibitor of aldehyde dehydrogenases 1 and 3
      on tumour cell growth and death.
AB  - Aldehyde dehydrogenases (ALDHs) are a family of several isoenzymes expressed in
      various tissues and in all subcellular fractions. In some tumours, there is an
      increase of ALDH activity, especially that of class 1 and 3. The increase in the
      activity of these isoenzymes is correlated with cell growth and drug resistance
      shown by these cells. It has been observed that hepatoma cells expressing low
      ALDH3 activity are more susceptible to growth inhibition by low concentration of
      lipid peroxidation products than hepatoma cells expressing high ALDH3 activity.
      The products of lipid peroxidation are good substrates for ALDH, but when their
      intracellular levels are increased in hepatoma cells treated repeatedly with
      prooxidants, they inhibit ALDH3 and bring about growth inhibition or cell death.
      As a follow up to the work previously reported on S-methyl 4-amino-4-methylpent-2
      ynethioate, a synthetic suicide inhibitor of ALDH1, which induced bcl2
      overexpressing cells into apoptosis and exhibited an ED50 of 400 microM, a novel
      broad spectrum inhibitor of ALDH1 and ALDH3 was synthesised. This new compound
      (ATEM) is a suicide inhibitor of ALDH1, an irreversible inhibitor of ALDH3 and
      exhibits an ED50 of 10-25 microM on rat cultured hepatoma cells. Four hours after
      treatment with 25 microM ATEM, ALDH activity using benzaldehyde or
      propionaldehyde in hepatoma cells was decreased by 40% and cell number by 15%
      compared with controls. As cell growth did not resume when the inhibitor was
      removed from the culture medium, it suggested strongly that ALDHs play a pivotal
      role in mediating cell death.

PMID- 11306046
TI  - Inhibition of cytosolic class 3 aldehyde dehydrogenase by antisense
      oligonucleotides in rat hepatoma cells.
AB  - Aldehyde dehydrogenases (ALDHs) are a superfamily of several isoenzymes widely
      expressed in bacteria, yeast, plant and animals. Three major classes of ALDHs
      have been traditionally identified, classes 1, 2 and 3. Both exogenous and
      endogenous aldehydes, including aldehydes derived from lipid peroxidation, are
      oxidized by the ALDH superfamily. Several changes in ALDH isoenzyme expression
      take place in hepatoma cells, in particular cytosolic class 3 ALDH (ALDH3), not
      expressed in normal hepatocytes, appears and increases with the degree of
      deviation. It has been demonstrated that cytosolic ALDH3 is important in
      determining the resistance of tumor cells to antitumor drugs, such as
      cyclophosphamide. Moreover, hepatoma-associated ALDH3 seems to be important in
      metabolizing aldehydes derived from lipid peroxidation, and in particular the
      cytostatic aldehyde 4-hydroxynonenal (4-HNE). We demonstrated previously that
      restoring endogenous lipid peroxidation in hepatoma cells by enriching them with
      arachidonic acid causes a decrease of mRNA, protein and enzyme activity of ALDH3
      and that this decrease reduces cell growth and/or causes cell death, depending on
      basal class 3 ALDH activity. To confirm the correlation between inhibition of
      class 3 ALDH and reduction of cell proliferation, we exposed hepatoma cells to
      antisense oligonucleotides (ODNs) against ALDH3. In JM2 hepatoma cell line, with
      high ALDH3 activity, the exposure to antisense ODNs significantly decreases mRNA
      and enzyme activity (90%). At the same time, cell growth was reduced by about
      70%. The results confirm that in hepatoma cells ALDH3 expression is closely
      related with cell growth, and that its inhibition is important in reducing the
      proliferation of hepatoma cells overexpressing ALDH3.

PMID- 11306047
TI  - Aldehyde dehydrogenase 3 gene regulation: studies on constitutive and hypoxia
      modulated expression.
AB  - We have previously shown that expression of the Class 3 aldehyde dehydrogenase
      gene (ALDH3) is abrogated by hypoxia. This phenomenon occurs in rat hepatoma
      systems in which ALDH3 expression is xenobiotic-inducible as well as in rat
      primary corneal epithelial cells that exhibit high constitutive ALDH3 expression.
      We have begun to test various segments of the ALDH3 5' flanking region for
      elements that may mediate this effect using CAT reporter gene constructs. In
      addition, although the involvement of the Ah receptor nuclear translocator (ARNT)
      in xenobiotic induction of ALDH3 is well established, the role of ARNT in
      constitutive ALDH3 expression is not clear. Moreover, ARNT is also a component of
      the hypoxia inducible factor-1 (HIF-1) bipartite transcription factor complex
      that mediates hypoxic induction of a variety of genes. Concomitant activation of
      the xenobiotic and hypoxia pathways results in cross-talk and functional
      interference. It has been hypothesized that this interference is due to limiting
      levels of ARNT. To examine if ARNT levels are limiting during hypoxic and
      xenobiotic induction in the context of ALDH3 expression and to examine possible
      roles of ARNT in constitutive expression of ALDH3 in corneal epithelial cells we
      co-transfected rat corneal epithelial cells and H4-II-EC3 rat hepatoma cells with
      ALDH3 5' UTR-CAT reporter genes and expression vectors containing either wild
      type or dominant negative forms of ARNT. Our results indicate that during hypoxia
      and xenobiotic induction of ALDH3 in H4-II-EC3 cells ARNT is not the limiting
      transcription factor. Further, neither wild type nor dominant negative ARNT had
      effects on constitutive ALDH3 expression in corneal epithelial cells.

PMID- 11306048
TI  - Effects of 3-methylcholanthrene and aspirin co-administration on ALDH3A1 in HepG2
      cells.
AB  - The effects of two different protocols of 3-methylcholanthrene (3MC) and aspirin
      co-administration were studied in a well-established human hepatoma cell line
      (HepG2). During this work, we have performed toxicity tests for cell
      viability/cell proliferation as well as studies on the expression of ALDH3A1
      after exposure of HepG2 cells to 3MC or/and aspirin. For the evaluation of toxic
      concentrations of 3MC and aspirin, the WST-1 test was used. WST-1 is a reliable
      cytotoxicity test which is based on the cleavage of the tetrazolium salt WST-1 to
      formazan by mitochondrial enzymes of living cells. A broad range of drug
      concentrations for either 3MC (0.25-50.0 microM) or aspirin (0.05-10.0 mM) were
      used for cell exposure, in several periods of time. The expression of ALDH3A1 in
      HepG2 cells showed typical time- and dose-response curves of induction after
      application of 3MC (1-5 days, 1.5-5.0 microM, respectively). When cells were
      firstly exposed to 3MC (2.5 and 5.0 microM) and then to aspirin (0.25 mM), the
      induced ALDH3A1 activity was further enhanced in a statistically significant way
      (P<0.05). On the contrary, when aspirin application was preceded 3MC exposuring a
      statistically significant decrease in ALDH3A1 inducibility was observed, as
      compared with the application of 3MC alone.

PMID- 11306049
TI  - Three different stable human breast adenocarcinoma sublines that overexpress
      ALDH3A1 and certain other enzymes, apparently as a consequence of constitutively
      upregulated gene transcription mediated by transactivated EpREs (electrophile
      responsive elements) present in the 5'-upstream regions of these genes.
AB  - ALDH3A1 catalyzes the detoxification of cyclophosphamide, mafosfamide, 4
      hydroperoxycyclophosphamide and other oxazaphosphorines. Constitutive ALDH3A1
      levels, as well as those of certain other drug-metabolizing enzymes, e.g. NQO1
      and CYP1A1, are relatively low in cultured, relatively oxazaphosphorine
      sensitive, human breast adenocarcinoma MCF-7 cells. However, transient cellular
      insensitivity to the oxazaphosphorines can be brought about in these cells by
      transiently elevating ALDH3A1 levels in them as a consequence of transient
      exposure to: (1) electrophiles such as catechol that induce the transcription of
      a battery of genes, e.g. ALDH3A1 and NQO1, having in common an electrophile
      responsive element (EpRE) in their 5'-upstream regions; or (2) Ah-receptor
      agonists, e.g. indole-3-carbinol and polycyclic aromatic hydrocarbons such as 3
      methylcholanthrene, that induce the transcription of a battery of genes, e.g.
      ALDH3A1, NQO1 and CYP1A1, having in common a xenobiotic responsive element (XRE)
      in their 5'-upstream regions. Further, MCF-7 sublines that are constitutively,
      i.e. when grown in the absence of the original selecting pressure, relatively
      oxazaphosphorine-insensitive as a consequence of constitutively relatively
      elevated cellular ALDH3A1 levels evolved when MCF-7 cells were: (1) continuously
      exposed for several months to gradually increasing concentrations of 4
      hydroperoxycyclophosphamide or benz(a)pyrene; or (2) briefly exposed (once for 30
      min) to a high concentration (1 mM) of mafosfamide. Each of these three stable
      sublines is constitutively relatively cross-insensitive to benz(a)pyrene and
      other polycyclic aromatic hydrocarbons. Cellular levels of NQO1, but not of
      CYP1A1, are also constitutively relatively elevated in each of the three
      sublines. RT-PCR-based experiments established that ALDH3A1 mRNA levels are
      constitutively elevated ( approximately 5- to 8-fold) in each of the three
      sublines. The elevated ALDH3A1 mRNA levels are not the consequence of gene
      amplification, hypomethylation of a relevant regulatory element, or ALDH3A1 mRNA
      stabilization. Collectively, these observations suggest that constitutively
      elevated levels of ALDH3A1 and certain other enzymes in the three stable sublines
      are probably the consequence of a constitutive change in the cellular
      concentration of a key component of the EpRE signaling pathway, such that the
      cellular concentration of the relevant ultimate transactivating factor is
      constitutively elevated, i.e. gene transcription promoted by transactivated EpREs
      is constitutively upregulated. Further, constitutively upregulated gene
      transcription mediated by transactivated EpREs can be relatively easily induced,
      whereas that mediated by transactivated XREs cannot, at least in MCF-7 cells.
      Still further, the three sublines may facilitate study of the signaling pathway
      that leads to transactivation of the EpREs present in the 5'-upstream regions of
      ALDH3A1, NQO1 and other gene loci.

PMID- 11306050
TI  - Selective protection by stably transfected human ALDH3A1 (but not human ALDH1A1)
      against toxicity of aliphatic aldehydes in V79 cells.
AB  - Toxic medium chain length alkanals, alkenals, and 4-hydroxyalkenals that are
      generated during lipid peroxidation are potential substrates for aldehyde
      dehydrogenase (ALDH) isoforms. We have developed transgenic cell lines to examine
      the potential for either human ALDH1A1 or ALDH3A1 to protect against damage
      mediated by these toxic aldehydes. Using crude cytosols from stably transfected
      cell lines, these aldehydes were confirmed to be excellent substrates for
      ALDH3A1, but were poorly oxidized by ALDH1A1. Expression of ALDH3A1 by stable
      transfection in V79 cells conferred a high level of protection against growth
      inhibition by the medium-chain length aldehyde substrates with highest substrate
      activity, including hexanal, trans-2-hexenal, trans-2-octenal, trans-2-nonenal,
      and 4-hydroxy-2-nonenal (HNE). This was reflected in a parallel ability of
      ALDH3A1 to prevent depletion of glutathione by these aldehydes. Expression of
      hALDH3 completely blocked the potent induction of apoptosis by HNE in both V79
      cells and in a RAW 264.7 murine macrophage cell line, consistent with the
      observed total prevention of HNE-protein adduct formation. Structure-activity
      studies indicated that the rank order of potency for the contributions of HNE
      functional groups to toxicity was aldehyde >/=C2=C3 double bond>>C4-hydroxyl
      group. Oxidation of the aldehyde moiety of HNE to a carboxyl by ALDH3A1 expressed
      in stably transfected cell lines drastically reduced its potency for growth
      inhibition and apoptosis induction. In contrast, ALDH1A1 expression provided only
      moderate protection against trans-2-nonenal (t2NE), and none against the other
      six-nine carbon aldehydes. Neither ALDH1A1 nor ALDH3A1 conferred any protection
      against acrolein, acetaldehyde, or chloroacetaldehyde. A small degree of
      protection against malondialdehyde was afforded by ALDH1A1, but not ALDH3A1.
      Paradoxically, cells expressing ALDH3A1 were 1.5-fold more sensitive to
      benzaldehyde toxicity than control V79 cells. These studies demonstrate that
      expression of class 3 ALDH, but not class 1 ALDH, can be an important determinant
      of cellular resistance to toxicity mediated by aldehydes of intermediate chain
      length that are produced during lipid peroxidation.

PMID- 11306051
TI  - Phenobarbital inducibility and differences in protein expression of an animal
      model.
AB  - Aldehyde dehydrogenases (ALDHs) are a group of enzymes which catalyze the
      conversion of aldehydes to the corresponding carboxylic acids in a NAD(P)(+)
      dependent reaction. In mammals, different ALDHs are constitutively expressed in
      liver, stomach, eye and skin. In addition, inducible ALDH-isoenzymes are
      detectable in many tissues; apart from other physico- and immuno-chemical
      differences, two cytosolic ALDHs (ALDH1A3 and ALDH3A1) are known to be activated
      in rat liver, by different types of inducers of drug metabolism. Phenobarbital
      type inducers increase the ALDH1A3, while polycyclic hydrocarbons (such as BaP
      and TCDD) increase the expression of the two members of ALDH3A subfamily (3A1 and
      3A2). In this study, we used two Wistar rat substrains which have been well
      characterized for different inducibility of ALDH1A3 enzyme activity after
      treatment with phenobarbital. Animals that respond (RR) or do not respond (rr) to
      treatment have been inbred for almost 25 years, offering a useful experimental
      model. Apart from the level of ALDH1A3 induced enzyme expression after
      phenobarbital treatment, no other differences between the two substrains have
      been noticed, as far as drug metabolizing enzyme activities (like the pentoxy-
      and ethoxy-O-dealkylation rate) are concerned. According to the present results,
      the ALDH1A3 expression is still the only difference between the two substrains.
      Immunoblotting experiments with polyclonal antibodies raised against CYP2B1
      or/and CYP1A1/1A2 showed no differences between the two substrains. Additionally,
      data concerning time- and dose-response induction of ALDH1A3 after phenobarbital
      and griseofulvin treatment are presented. It is concluded that these two Wistar
      rat substrains represent a unique animal model for studying what seems to be the
      only difference between these substrains - the genetic basis of the phenobarbital
      induction.

PMID- 11306052
TI  - The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic
      mechanism in isolated rat hepatocytes.
AB  - The toxicity and carcinogenicity of formaldehyde (HCHO) has been attributed to
      its ability to form adducts with DNA and proteins. A marked decrease in
      mitochondrial membrane potential and inhibition of mitochondrial respiration that
      was accompanied by reactive oxygen species formation occurred when isolated rat
      hepatocytes were incubated with low concentrations of HCHO in a dose-dependent
      manner. Hepatocyte GSH was also depleted by HCHO in a dose-dependent manner. At
      higher HCHO concentrations, lipid peroxidation ensued followed by cell death.
      Cytotoxicity studies were conducted in which isolated hepatocytes exposed to HCHO
      were treated with inhibitors of HCHO metabolising enzymes. There was a marked
      increase in HCHO cytotoxicity when either alcohol dehydrogenase or aldehyde
      dehydrogenase was inhibited. Inhibition of GSH-dependent HCHO dehydrogenase
      activity by prior depletion of GSH markedly increased hepatocyte susceptibility
      to HCHO. In each case, cytotoxicity was dose-dependent and corresponded with a
      decrease in hepatocyte HCHO metabolism and increased lipid peroxidation.
      Antioxidants and iron chelators protected against HCHO cytotoxicity. Cytotoxicity
      was also prevented, when cyclosporine or carnitine was added to prevent the
      opening of the mitochondrial permeability transition pore which further suggests
      that HCHO targets the mitochondria. Thus, HCHO-metabolising gene polymorphisms
      would be expected to have toxicological consequences on an individual's
      susceptibility to HCHO toxicity and carcinogenesis.

PMID- 11306053
TI  - Fatty aldehyde dehydrogenase: genomic structure, expression and mutation analysis
      in Sjogren-Larsson syndrome.
AB  - Fatty aldehyde dehydrogenase (FALDH) is a microsomal enzyme that catalyzes the
      oxidation of medium- and long-chain aliphatic aldehydes derived from metabolism
      of fatty alcohol, phytanic acid, ether glycerolipids and leukotriene B4. The
      FALDH gene (ALDH3A2) in man and mouse consists of 11 exons and is closely linked
      to the gene for ALDH3. In both species, alternative splicing results in formation
      of a second minor protein, FALDHv, that has a unique carboxy-terminal end. The
      functional significance of this alternate protein is not known. In humans,
      mutations in the FALDH gene cause Sjogren-Larsson syndrome (SLS), which is
      characterized by ichthyosis, mental retardation and spasticity. Missense
      mutations involving 24 amino acid positions in FALDH have been identified. These
      amino acids are more highly conserved among related class 3 aldehyde
      dehydrogenase enzymes than expected, suggesting that they are critically
      important for protein folding, catalysis or stability. Studies of mutations in
      SLS should prove useful for understanding structure-function correlations in
      FALDH and other aldehyde dehydrogenase proteins.

PMID- 11306054
TI  - Characterization of Xenopus cytosolic thyroid-hormone-binding protein (xCTBP)
      with aldehyde dehydrogenase activity.
AB  - Multiple cytosolic thyroid-hormone-binding proteins (CTBPs) with varying
      characteristics, depending on the species and tissue, have been reported. We
      first purified a 59-kDa CTBP from Xenopus liver (xCTBP), and found that it is
      responsible for major [125I]T(3)-binding activity in Xenopus liver cytosol. Amino
      acid sequencing of internal peptide fragments derived from xCTBP demonstrated
      high identity to the corresponding sequence of mammalian aldehyde dehydrogenases
      1 (ALDH1). To confirm whether or not xCTBP is identical to xALDH1, we isolated
      cDNAs encoding xALDH1 from an adult Xenopus hepatic cDNA library. The amino acid
      sequences deduced from the two isolated xALDH1 cDNAs were very similar to those
      of mammalian ALDH1 enzymes. The recombinant xALDH1 protein exhibited both T(3)
      binding activity and ALDH activity converting retinal to retinoic acid (RA),
      which were similar to those of xCTBP purified from liver cytosol. The T(3)
      binding activity was inhibited by NAD, while the ALDH activity was inhibited by
      thyroid hormones. Our results demonstrate that xCTBP is identical to ALDH1 and
      suggest that this protein might modulate RA synthesis and intracellular
      concentration of free T(3). Communications between thyroid hormone and retinoid
      pathways are discussed.

PMID- 11306055
TI  - Aldehyde dehydrogenase gene superfamily: the 2000 update.
AB  - Aldehyde dehydrogenase (ALDH) superfamily represents a group of NAD(P)(+)
      dependent enzymes that catalyze the oxidation of a wide spectrum of endogenous
      and exogenous aldehydes. With the advent of megabase genome sequencing, the ALDH
      superfamily is expanding rapidly on many fronts. As expected, ALDH genes are
      found in virtually all genomes analyzed to date, indicating the importance of
      these enzymes in biological functions. Complete genome sequences of various
      species have revealed additional ALDH genes. As of July 2000, the ALDH
      superfamily consists of 331 distinct genes, of which eight are found in archaea,
      165 in eubacteria, and 158 in eukaryota. The number of ALDH genes in some species
      with their genomes completely sequenced and annotated, Escherichia coli and
      Caenorhabditis elegans, ranges from 10 to 17. In the human genome, 17 functional
      genes and three pseudogenes have been identified to date. Divergent evolution,
      based on multiple alignment analysis of 86 eukaryotic ALDH amino-acid sequences,
      was the basis of the standardized ALDH gene nomenclature system (Pharmacogenetics
      9: 421-434, 1999). Thus far, the eukaryotic ALDHs comprise 20 gene families. A
      complete list of all ALDH sequences known to date is presented here along with
      the evolution analysis of the eukaryotic ALDHs.

PMID- 11306056
TI  - Class II alcohol dehydrogenase (ADH2)--adding the structure.
AB  - Class II alcohol dehydrogenase (ADH2) represents a highly divergent class of
      alcohol dehydrogenases predominantly found in liver. Several species variants of
      ADH2 have been described, and the rodent enzymes form a functionally distinct
      subgroup with interesting catalytic properties. First, as compared with other
      ADHs, the catalytic efficiency is low for this subgroup. Second, the substrate
      repertoire is unique, e.g. rodent ADH2s are not saturated with ethanol as
      substrate, and while omega-hydroxy fatty acids are common substrates for the
      human ADH1-ADH4 isoenzymes, including ADH2, these compounds function as
      inhibitors rather than substrates. The recently determined structure of mouse
      ADH2 reveals a novel substrate-pocket topography that accounts for the observed
      substrate specificity and may, therefore, be important for the exploration of
      orphan substrates of ADH2. It is possible to improve the catalytic efficiency of
      mouse ADH2 by an array of mutations at position 47. Residue Pro47 of the wild
      type ADH2 enzyme seems to strain the binding of coenzyme, which prevents a close
      approach between the coenzyme and substrate for efficient hydrogen transfer.
      Based on crystallographic and mechanistic investigations, the effects of residue
      replacements at position 47 are multiple, affecting the distance for hydride
      transfer, the pK(a) of the bound alcohol substrate as well as the affinity for
      coenzyme.

PMID- 11306057
TI  - Crystal structure of sorbitol dehydrogenase.
AB  - Sorbitol dehydrogenase (SDH) is a distant relative to the alcohol dehydrogenases
      (ADHs) with sequence identities around 20%. SDH is a tetramer with one zinc ion
      per subunit. We have crystallized rat SDH and determined the structure by
      molecular replacement using a tetrameric bacterial ADH as search object. The
      conformation of the bound coenzyme is extended and similar to NADH bound to
      mammalian ADH but the interactions with the NMN-part have several differences
      with those of ADH. The active site zinc coordination in SDH is significantly
      different than in mammalian ADH but similar to the one found in the bacterial
      tetrameric NADP(H)-dependent ADH of Clostridiim beijerinckii. The substrate cleft
      is significantly more polar than for mammalian ADH and a number of residues are
      ideally located to position the sorbitol molecule in the active site. The SDH
      molecule can be considered to be a dimer of dimers, with subunits A-B and C-D,
      where the dimer interactions are similar to those in mammalian ADH. The tetramers
      are composed of two of these dimers, which interact with their surfaces opposite
      the active site clefts, which are accessible on the opposite side. In contrast to
      the dimer interactions, the tetramer-forming interactions are small with only few
      hydrogen bonds between side-chains.

PMID- 11306058
TI  - Characterization of a microsomal retinol dehydrogenase gene from amphioxus:
      retinoid metabolism before vertebrates.
AB  - Amphioxus, a member of the subphylum Cephalochordata, is thought to be the
      closest living relative to vertebrates. Although these animals have a vertebrate
      like response to retinoic acid, the pathway of retinoid metabolism remains
      unknown. Two different enzyme systems - the short chain dehydrogenase/reductases
      and the cytosolic medium-chain alcohol dehydrogenases (ADHs) - have been
      postulated in vertebrates. Nevertheless, recent data show that the vertebrate
      ADH1 and ADH4 retinol-active forms originated after the divergence of
      cephalochordates and vertebrates. Moreover, no data has been gathered in support
      of medium-chain retinol active forms in amphioxus. Then, if the cytosolic ADH
      system is absent and these animals use retinol, the microsomal retinol
      dehydrogenases could be involved in retinol oxidation. We have identified the
      genomic region and cDNA of an amphioxus Rdh gene as a preliminary step for
      functional characterization. Besides, phylogenetic analysis supports the
      ancestral position of amphioxus Rdh in relation to the vertebrate forms.

PMID- 11306059
TI  - Ternary complexes of liver alcohol dehydrogenase.
AB  - Liver alcohol dehydrogenase (LADH; E.C. 1.1.1.1) provides an excellent system for
      probing the role of binding interactions with NAD(+) and alcohols as well as with
      NADH and the corresponding aldehydes. The enzyme catalyzes the transfer of
      hydride ion from an alcohol substrate to the NAD(+) cofactor, yielding the
      corresponding aldehyde and the reduced cofactor, NADH. The enzyme is also an
      excellent catalyst for the reverse reaction. X-ray crystallography has shown that
      the NAD(+) binds in an extended conformation with a distance of 15 A between the
      buried reacting carbon of the nicotinamide ring and the adenine ring near the
      surface of the horse liver enzyme. A major criticism of X-ray crystallographic
      studies of enzymes is that they do not provide dynamic information. Such data
      provide time-averaged and space-averaged models. Significantly, entries in the
      protein data bank contain both coordinates as well as temperature factors.
      However, enzyme function involves both dynamics and motion. The motions can be as
      large as a domain closure such as observed with liver alcohol dehydrogenase or as
      small as the vibrations of certain atoms in the active site where reactions take
      place. Ternary complexes produced during the reaction of the enzyme binary
      entity, E-NAD(+), with retinol (vitamin A alcohol) lead to retinal (vitamin A
      aldehyde) release and the enzyme binary entity E-NADH. Retinal is further
      metabolized via the E-NAD(+)-retinal ternary complex to retinoic acid (vitamin A
      acid). To unravel the mechanistic aspects of these transformations, the kinetics
      and energetics of interconversion between various ternary complexes are
      characterized. Proton transfers along hydrogen bond bridges and NADH hydride
      transfers along hydrophobic entities are considered in some detail. Secondary
      kinetic isotope effects with retinol are not particularly large with the wild
      type form of alcohol dehydrogenase from horse liver. We analyze alcohol
      dehydrogenase catalysis through a re-examination of the reaction coordinates. The
      ground states of the binary and ternary complexes are shown to be related to the
      corresponding transition states through topology and free energy acting along the
      reaction path.

PMID- 11306060
TI  - Bioinorganic and bioorganic studies of liver alcohol dehydrogenase.
AB  - Liver alcohol dehydrogenase (E.C.1.1.1.1) is an NAD(+)/NADH dependent enzyme with
      a broad substrate specificity being active on an assortment of primary and
      secondary alcohols. It catalyzes the reversible oxidation of a wide variety of
      alcohols to the corresponding aldehydes and ketones as well as the oxidation of
      certain aldehydes to their related carboxylic acids. Although the bioinorganic
      and bioorganic aspects of the enzymatic mechanism, as well as the structures of
      various ternary complexes, have been extensively studied, the kinetic
      significance of certain intermediates has not been fully evaluated. Nevertheless,
      the availability of computer-assisted programs for kinetic simulation and
      molecular modeling make it possible to describe the biochemical mechanism more
      completely. Although the true physiological substrates of this zinc metalloenzyme
      are unknown, alcohol dehydrogenase effectively catalyzes not only the
      interconversion of all-trans-retinol and all-trans-retinal but also the oxidation
      of all-trans-retinal to the corresponding retinoic acid. Retinal and related
      vitamin A derivatives play fundamental roles in many physiological processes,
      most notably the vision process. Furthermore, retinoic acid is used in
      dermatology as well as in the prevention and treatment of different types of
      cancer. The enzyme-NAD(+)-retinol complex has an apparent pK(a) value of 7.2 and
      loses a proton rapidly. Proton inventory modeling suggests that the transition
      state for the hydride transfer step has a partial negative charge on the oxygen
      of retinoxide. Spectral evidence for an intermediate such as E-NAD(+)-retinoxide
      was obtained with enzyme that has cobalt(II) substituted for the active site
      zinc(II). Biophysical considerations of water in these biological processes
      coupled with the inverse solvent isotope effect lead to the conclusion that the
      zinc-bound alkoxide makes a strong hydrogen bond with the hydroxyl group of Ser48
      and is thus activated for hydride transfer. Moderate pressure accelerates enzyme
      action indicative of a negative volume of activation. The data with retinol is
      discussed in terms of enzyme stability, mechanism, adaptation to extreme
      conditions, as well as water affinities of substrates and inhibitors. Our data
      concern all-trans, 9-cis, 11-cis, and 13-cis retinols as well as the
      corresponding retinals. In all cases the enzyme utilizes an approximately ordered
      mechanism for retinol-retinal interconversion and for retinal-retinoic acid
      transformation.

PMID- 11306061
TI  - Mammalian alcohol dehydrogenase of higher classes: analyses of human ADH5 and rat
      ADH6.
AB  - Alcohol dehydrogenases (ADH) of classes V and VI, ADH5 and ADH6, have been
      defined in man and rodents, respectively. Sequence data have been obtained at
      cDNA and genomic levels, but limited data are available for functionality and
      substrate repertoire. The low positional identity (65%) between the two ADHs,
      place them into separate classes. We have shown that the ADH5 gene yields two
      differently processed mRNAs and harbors a gene organization identical to other
      mammalian ADHs. This is probably due to an alternative splicing in the eighth
      intron that results in a shorter message missing the ninth exon or a normal
      message with the expected number of codons. The isolated rat ADH6 cDNA was found
      to be fused to ADH2 at the 5'-end. The resulting main open reading frame
      translates into an N-terminally extended polypeptide. In vitro translation
      results in a polypeptide of about 42 kDa and further, protein was possible to
      express in COS cells as a fusion product with Green Fluorescent Protein. Both
      ADH5 and ADH6 show genes and gene products that are processed comparably to other
      mammalian ADHs and the deduced amino acid sequences indicate a lack of ethanol
      dehydrogenase activity that probably explains why no corresponding proteins have
      been isolated. The functionality of these ADHs is therefore still an enigma.

PMID- 11306062
TI  - Genesis of Drosophila ADH: the shaping of the enzymatic activity from a SDR
      ancestor.
AB  - Drosophila alcohol dehydrogenase (ADH) is an NAD(H)-dependent oxidoreductase that
      catalyzes the oxidation of alcohols and aldehydes. Structurally and biochemically
      distinct from all the reported ADHs (typically, the mammalian medium-chain
      dehydrogenase/reductase-ethanol-metabolizing enzyme), it stands as the only small
      alcohol transforming system that has originated from a short-chain
      dehydrogenase/reductase (SDR) ancestor. The crystal structures of the apo, binary
      (E.NAD(+)) and three ternary (E.NAD(+).acetone, E.NAD(+).3-pentanone and
      E.NAD(+).cyclohexanone) forms of Drosophila lebanonensis ADH have allowed us to
      infer the structural and kinetic features accounting for the generation of the
      ADH activity within the SDR lineage.

PMID- 11306063
TI  - The activity of yeast ADH I and ADH II with long-chain alcohols and diols.
AB  - The activities of yeast ADH I and ADH II towards long chain alcohols and diols
      were studied using rather unusual conditions (1.0 M Tris pH 8.75, approximately
      0.3 mg/ml enzyme and [S]<<<K(m) ) where the alcohols are oxidised quantitatively
      in a first-order manner. Plots of the apparent first-order rate constant versus
      primary alcohol chain length show double peaks with similar values for ethanol
      and 1-decanol and relatively low values for 1-butanol through to 1-octanol. With
      the alpha,omega diols only one peak of activity was observed with 1,14
      tetradecanediol, the preferred substrate, being oxidised about the same rate as
      ethanol. Both enzymes were essentially inactive with short-chain diols (C(2)
      C(8)). For all of these assays normalised rates with ADH II were about threefold
      faster than with ADH I.

PMID- 11306064
TI  - Characterization and functional role of Saccharomyces cerevisiae 2,3-butanediol
      dehydrogenase.
AB  - Using a conserved sequence motif, a new gene (YAL060W) of the MDR family has been
      identified in Saccharomyces cerevisiae. The expressed protein was a
      stereoespecific (2R,3R)-2,3-butanediol dehydrogenase (BDH). The best substrates
      were (2R,3R)-2,3-butanediol for the oxidation and (3R/3S)-acetoin and 1-hydroxy-2
      propanone for the reduction reactions. The enzyme is extremely specific for
      NAD(H) as cofactor, probably because the presence of Glu223 in the cofactor
      binding site, instead of the highly conserved Asp223. BDH is inhibited
      competitively by 4-methylpyrazole with a K(i) of 34 microM. Yeast could grow on
      2,3-butanediol or acetoin as a sole energy and carbon sources, and a 3.6-fold
      increase in BDH activity was observed when cells were grown in 2,3-butanediol,
      suggesting a role of the enzyme in 2,3-butanediol metabolism. However, the
      disruption of the YAL060W gene was not lethal for the yeast under laboratory
      conditions, and the disrupted strain could also grow in 2,3-butanediol and
      acetoin. This suggests that other enzymes, in addition to BDH, can also
      metabolize 2,3-butanediol in yeast.

PMID- 11306065
TI  - Kinetic effects of a single-amino acid mutation in a highly variable loop
      (residues 114-120) of class IV ADH.
AB  - Class IV alcohol dehydrogenase shows a deletion at position 117 with respect to
      class I enzymes, which typically have a Gly residue. In class I structures,
      Gly117 is part of a loop (residues 114-120) that is highly variable within the
      alcohol dehydrogenase family. A mutant human class IV enzyme was engineered in
      which a Gly residue was inserted at position 117 (G117ins). Its kinetic
      properties, regarding ethanol and primary aliphatic alcohols, secondary alcohols
      and pH profiles, were determined and compared with the results obtained in
      previous studies in which the size of the 114-120 loop was modified. For the
      enzymes considered, a smaller loop was associated with a lower catalytic
      efficiency towards short-chain alcohols (ethanol and propanol) and secondary
      alcohols, as well as with a higher K(m) for ethanol at pH 7.5 than at pH 10.0.
      The effect can be rationalized in terms of a more open, solvent-accessible active
      site in class IV alcohol dehydrogenase, which disfavors productive binding of
      ethanol and short-chain alcohols, specially at physiological pH.

PMID- 11306066
TI  - Mouse alcohol dehydrogenase 4: kinetic mechanism, substrate specificity and
      simulation of effects of ethanol on retinoid metabolism.
AB  - Mouse ADH4 (purified, recombinant) has a low catalytic efficiency for ethanol and
      acetaldehyde, but very high activity with longer chain alcohols and aldehydes, at
      pH 7.3 and temperature 37 degrees C. The observed turnover numbers and catalytic
      efficiencies for the oxidation of all-trans-retinol and the reduction of all
      trans-retinal and 9-cis-retinal are low relative to other substrates; 9-cis
      retinal is more reactive than all-trans-retinal. The reduction of all-trans- or 9
      cis-retinals coupled to the oxidation of ethanol by NAD(+) is as efficient as the
      reduction with NADH. However, the Michaelis constant for ethanol is about 100 mM,
      which indicates that the activity would be lower at physiologically relevant
      concentrations of ethanol. Simulations of the oxidation of retinol to retinoic
      acid with mouse ADH4 and human aldehyde dehydrogenase (ALDH1), using rate
      constants estimated for all steps in the mechanism, suggest that ethanol (50 mM)
      would modestly decrease production of retinoic acid. However, if the K(m) for
      ethanol were smaller, as for human ADH4, the rate of retinol oxidation and
      formation of retinoic acid would be significantly decreased during metabolism of
      50 mM ethanol. These studies begin to describe quantitatively the roles of
      enzymes involved in the metabolism of alcohols and carbonyl compounds.

PMID- 11306067
TI  - Cloning of the human RoDH-related short chain dehydrogenase gene and analysis of
      its structure.
AB  - We have previously characterized the first human NAD(+)-dependent short chain
      dehydrogenase capable of oxidizing all-trans-retinol and androgens, and found
      only in the liver and skin. In a search for related human enzymes, we identified
      a partial open reading frame, which exhibited >60% sequence identity to human
      RoDH-4. The full-length cDNA for this enzyme was determined in our laboratory by
      5'-RACE PCR and was found to be identical to the recently reported novel type of
      oxidative human 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Analysis of the
      genomic structure revealed that the gene for RoDH-like 3alpha-HSD has four
      translated exons and, possibly, a fifth exon that codes for the 5'-untranslated
      region. The gene for RoDH-4 appears to have only four exons. The positions of
      exon-intron boundaries and the sizes of the protein coding regions are identical
      in 3alpha-HSD and RoDH-4. Moreover, both genes are mapped to chromosome 12q13,
      and are located in a close proximity to each other. Both genes appear to have
      satellite pseudogenes. Thus, RoDH-4 and 3alpha-HSD genes share similar structural
      organization and cluster on human chromosome 12, near the gene for 11-cis retinol
      dehydrogenase.

PMID- 11306068
TI  - Genetic dissection of retinoid dehydrogenases.
AB  - Biochemical studies indicate that alcohol dehydrogenase (ADH) metabolizes retinol
      to retinal, and that aldehyde dehydrogenase (ALDH) metabolizes retinal to
      retinoic acid, a molecule essential for growth and development. Summarized herein
      are several genetic studies supporting in vivo functions for ADH and ALDH in
      retinoic acid synthesis. Gene targeting was used to create knockout mice for
      either Adh1 or Adh4. Both knockout mice were viable and fertile without obvious
      defects. However, when wild-type and Adh4 knockout mice were subjected to vitamin
      A deficiency during gestation, the survival rate at birth was 3.3-fold lower for
      Adh4 knockout mice. When adult mice were examined for production of retinoic acid
      following retinol administration, Adh1 knockout mice exhibited 10-fold lower
      retinoic acid levels in liver compared with wild-type, whereas Adh4 knockout mice
      differed from wild-type by less than 2-fold. Thus, Adh1 plays a major role in the
      metabolism of a large dose of retinol to retinoic acid in adults, whereas Adh4
      plays a role in maintaining sufficient retinol metabolism for development during
      retinol deficiency. ALDHs were examined by overexpression studies in frog
      embryos. Injection of mRNAs for either mouse Raldh1 or Raldh2 stimulated retinoic
      acid synthesis in frog embryos at the blastula stage when retinoic acid is
      normally undetectable. Overexpression of human ALDH2, human ALDH3, and mouse Aldh
      pb did not stimulate retinoic acid production. In addition, Raldh2 knockout mice
      exhibit embryonic lethality with defects in retinoid-dependent tissues. Overall,
      these studies provide genetic evidence that Adh1, Adh4, Raldh1, and Raldh2 encode
      retinoid dehydrogenases involved in retinoic acid synthesis in vivo.

PMID- 11306069
TI  - Identification and expression of cosmids with an allelic variant of class I
      alcohol dehydrogenase in transgenic mice.
AB  - The mouse Adh1 gene exhibits tissue-specific regulation, is developmentally
      regulated, and is androgen regulated in kidney and adrenal tissue. To study this
      complex regulation phenotype a transgenic mouse approach has been used to
      investigate regulatory regions of the gene necessary for proper tissue expression
      and hormonal control. Transgenic mice have been produced with an Adh1 minigene as
      a reporter behind either 2.5- or 10 kb of 5'-flanking sequence [1]. Complete
      androgen regulation in kidney requires a region between -2.5 and -10 kb. A
      sequence extending to -10 kb does not confer liver expression in this minigene
      construct. B6.S mice express an electrophoretically variant protein resulting
      from a known nucleotide substitution resulting in a restriction endonuclease
      length polymorphism. Transgenic mice harboring B6.S cosmids can be studied for
      expression analysis at both protein and mRNA levels, identification of transgenic
      founders and inheritance studies are greatly facilitated by a PCR-restriction
      endonuclease cleavage approach, the entire mouse gene is used as a reporter, and
      the formation of heterodimeric enzyme molecules can be used to infer expression
      of the transgene in the proper cell types within a given tissue. Expression of a
      B6.S cosmid containing the entire Adh1 gene and 6 kb of 5'- and 21 kb of 3'
      flanking region occurs in transgenic mice in a copy number dependent manner in a
      number of tissues, but expression in liver does not occur. The ability to analyze
      expression at the protein and mRNA levels has been confirmed using this system.
      Future directions will involve the use of large BAC clones modified by RARE
      cleavage to identify the liver specific elements necessary for expression.

PMID- 11306070
TI  - Variations and constant patterns in eukaryotic MDR enzymes. Conclusions from
      novel structures and characterized genomes.
AB  - Medium-chain dehydrogenases/reductases (MDR) alcohol dehydrogenases exhibit
      multiple forms through a number of gene duplications. A crucial duplication was
      the one leading from the glutathione-dependent formaldehyde dehydrogenase line to
      the liver alcohol dehydrogenase (ADH) lines of vertebrates, the first duplication
      of which can now be further positioned at early vertebrate times. Similarly,
      screening of MDR forms in recently completed eukaryotic genomes of Caenorhabditis
      elegans and Drosophila melanogaster suggest that the MDR family may constitute a
      moderately sized protein family centered around a limited number of enzyme
      activities of five different structural types.

PMID- 11306071
TI  - The aldo-keto reductase (AKR) superfamily: an update.
AB  - The aldo-keto reductases (AKRs) are one of three enzyme superfamilies
      encompassing a range of oxidoreductases. Members of the AKR superfamily are
      monomeric (alpha/beta)(8)-barrel proteins, about 320 amino acids in length, which
      bind NAD(P)(H) to metabolize an array of substrates. AKRs have been identified in
      vertebrates, invertebrates, plants, protozoa, fungi, eubacteria, and
      archaebacteria, implying that this is an ancient superfamily of enzymes. Earlier,
      in an attempt to clarify the confusion caused by multiple names for particular
      AKRs, we proposed a systematic and expandable nomenclature system to assign
      consistent designations to unique members of the AKR superfamily. Since then, the
      number of characterized AKRs has expanded to 105 proteins in 12 families. In
      addition, molecular cloning and genome sequencing projects have identified 125
      potential AKR genes, many of which have no assigned function. The nomenclature
      system for the AKR superfamily is accepted by the Human Genome Project. Using the
      earlier described nomenclature system, we now provide an updated listing of AKRs
      and potential superfamily members.

PMID- 11306072
TI  - The crystal structure of the GCY1 protein from S. cerevisiae suggests a divergent
      aldo-keto reductase catalytic mechanism.
AB  - The crystal structure of the GCY1 gene product from Saccharomyces cerevisiae has
      been determined to 2.5 A and is being refined. The model includes two protein
      molecules, one apo and one holo, per asymmetric unit. Examination of the model
      reveals that the active site surface is somewhat flat when compared with the
      other aldo-keto reductase structures, possibly accommodating larger substrates.
      The K(m) for NADPH (28.5 microM) is higher than that seen for other family
      members. This can be explained structurally by the lack of the 'safety belt' of
      residues seen in other aldo-keto reductases with higher affinity for NADPH.
      Catalysis also differs from the other aldo-keto reductases. The tyrosine that
      acts as an acid in the reduction reaction is flipped out of the catalytic pocket.
      This implies that the protein must either undergo a conformational change before
      catalysis can take place or that there is an alternate acid moiety.

PMID- 11306073
TI  - Characterization of the glutathione binding site of aldose reductase.
AB  - Despite extensive investigations, the physiological role of the polyol pathway
      enzyme-aldose reductase (AR) remains obscure. While the enzyme reduces glucose in
      vivo and in vitro, kinetic and structural studies indicate inefficient
      carbohydrate binding to the active site of the enzyme. The active site is lined
      by hydrophobic residues and appears more compatible with the binding of medium-
      to long-chain aliphatic aldehydes or hydrophobic aromatic aldehydes. In addition,
      our recent studies show that glutathione (GS) conjugates are also reduced
      efficiently by the enzyme. For instance, the GS conjugate of acrolein is reduced
      with a catalytic efficiency 1000-fold higher than the parent aldehyde, indicating
      specific recognition of glutathione by the active site residues of AR. An
      increase in the catalytic efficiency upon glutathiolation was also observed with
      trans-2-nonenal, trans-2-hexenal and trans, trans-2,4-decadienal, establishing
      that enhancement of catalytic efficiency was specifically due to the glutathione
      backbone and not specific to the aldehyde. Structure-activity relationships with
      substitution or deletion of amino acids of GSH indicated specific interactions of
      the active site with gamma-Glu1 and Cys of GSH. Molecular modeling revealed that
      the glutathione-propanal conjugate could bind in two distinct orientations. In
      orientation 1, gamma-Glu1 of the conjugate interacts with Trp20, Lys21 and Val47,
      and Gly3 interacts with Ser302 and Leu301, whereas in orientation 2, the molecule
      is inverted with gamma-Glu1 interacting with Ser302, and Leu301. Taken together,
      these data suggest that glutathiolation of aldehydes enhances their compatibility
      with the AR active site, which may be of physiological significance in
      detoxification of endogenous and xenobiotic aldehydes.

PMID- 11306074
TI  - Metabolism of the 2-oxoaldehyde methylglyoxal by aldose reductase and by
      glyoxalase-I: roles for glutathione in both enzymes and implications for diabetic
      complications.
AB  - Numerous physiological aldehydes besides glucose are substrates of aldose
      reductase, the first enzyme of the polyol pathway which has been implicated in
      the etiology of diabetic complications. The 2-oxoaldehyde methylglyoxal is a
      preferred substrate of aldose reductase but is also the main physiological
      substrate of the glutathione-dependent glyoxalase system. Aldose reductase
      catalyzes the reduction of methylglyoxal efficiently (k(cat)=142 min(-1) and
      k(cat)/K(m)=1.8x10(7) M(-1) min(-1)). In the presence of physiological
      concentrations of glutathione, methylglyoxal is significantly converted into the
      hemithioacetal, which is the actual substrate of glyoxalase-I. However, in the
      presence of glutathione, the efficiency of reduction of methylglyoxal, catalyzed
      by aldose reductase, also increases. In addition, the site of reduction switches
      from the aldehyde to the ketone carbonyl. Thus, glutathione converts aldose
      reductase from an aldehyde reductase to a ketone reductase with methylglyoxal as
      substrate. The relative importance of aldose reductase and glyoxalase-I in the
      metabolic disposal of methylglyoxal is highly dependent upon the concentration of
      glutathione, owing to the non-catalytic pre-enzymatic reaction between
      methylglyoxal and glutathione.

PMID- 11306075
TI  - Involvement of aldose reductase in the metabolism of atherogenic aldehydes.
AB  - Phospholipid peroxidation generates a variety of aldehydes, which includes free
      saturated and unsaturated aldehydes, and aldehydes that remain esterified to the
      phosphoglyceride backbone - the so-called 'core' aldehydes. However, little is
      known in regarding the vascular metabolism of these aldehydes. To identify
      biochemical pathways that metabolize free aldehydes, we examined the metabolism
      of 4-hydroxy-trans-2-nonenal in human aortic endothelial cells. Incubation of
      these cells with [3H]-HNE led to the generation of four main metabolites, i.e.
      glutathionyl HNE (GS-HNE), glutathionyl dihydroxynonene (GS-DHN), DHN and 4
      hydroxynonanoic acid (HNA), which accounted for 5, 50, 6, and 23% of the total
      HNE metabolized. The conversion of GS-HNE to GS-DHN was inhibited by tolrestat,
      indicating that it is catalyzed by aldose reductase (AR). The AR was also found
      to be an efficient catalyst for the reduction of the core aldehyde - 1-palmitoyl
      2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine, which is generated in
      minimally modified low-density lipoprotein, and activates the endothelium to bind
      monocytes. As determined by electrospray mass spectrometry, reduction of POVPC
      (m/z=594) by AR led to the formation of 1-palmitoyl-2- (5)-hydrovaleryl-sn
      glycero-3-phosphorylcholine (PHVPC; m/z=596). These observations suggest that due
      to its ability to catalyze the reduction of lipid-derived aldehydes AR may be
      involved in preventing inflammation and diminishing oxidative stress during the
      early phases of atherogenesis.

PMID- 11306076
TI  - Metabolic regulation of aldose reductase activity by nitric oxide donors.
AB  - Regulation of aldose reductase (AR), a member of the aldo-keto reductase
      superfamily, by nitric oxide (NO) donors was examined. Incubation of human
      recombinant AR with S-nitrosoglutathione (GSNO) led to inactivation of the enzyme
      and the formation of an AR-glutathione adduct. In contrast, incubation with S
      nitroso-N-acetyl penicillamine (SNAP) or N-(beta-D-glucopyranosyl)-SNAP
      (GlycoSNAP) led to an increase in enzyme activity which was accompanied by the
      direct nitrosation of the enzyme and the formation of a mixed disulfide with the
      NO-donor. To examine in vivo modification, red blood cells (RBC) and rat aortic
      vascular smooth muscle cells (VSMC) were incubated with 1 mM GSNO or SNAP.
      Exposure of VSMC to SNAP and GSNO for 2 h at 37 degrees C led to approximately
      71% decrease in the enzyme activity with DL-glyceraldehyde as the substrate.
      Similarly, exposure of RBC in 5 mM glucose to NO-donors for 30 min at room
      temperature, followed by increasing the glucose concentration to 40 mM, resulted
      in >75% decrease in the formation of sorbitol. These investigations indicate that
      NO and/or its bioactive metabolites can regulate cellular AR, leading to either
      activation (by nitrosation) or inactivation (by S-thiolation).

PMID- 11306077
TI  - Structural and functional properties of aldose xylose reductase from the D-xylose
      metabolizing yeast Candida tenuis.
AB  - The primary structure of the aldose xylose reductase from Candida tenuis (CtAR)
      is shown to be 39% identical to that of human aldose reductase (hAR). The
      catalytic tetrad of hAR is completely conserved in CtAR (Tyr51, Lys80, Asp46,
      His113). The amino acid residues involved in binding of NADPH by hAR (D.K.
      Wilson, et al., Science 257 (1992) 81-84) are 64% identical in CtAR. Like hAR the
      yeast enzyme is specific for transferring the 4-pro-R hydrogen of the coenzyme.
      These properties suggest that CtAR is a member of the aldo/keto reductase
      superfamily. Unlike hAR the enzyme from C. tenuis has a dual coenzyme specificity
      and shows similar specificity constants for NADPH and NADH. It binds NADP(+)
      approximately 250 times less tightly than hAR. Typical turnover numbers for
      aldehyde reduction by CtAR (15-20 s(-1)) are up to 100-fold higher than
      corresponding values for hAR, probably reflecting an overall faster dissociation
      of NAD(P)(+) in the reaction catalyzed by the yeast enzyme.

PMID- 11306078
TI  - Modulation of aldose reductase activity through S-thiolation by physiological
      thiols.
AB  - The glutathionyl-modified aldose reductase (GS-ALR2) is unique, among different S
      thiolated enzyme forms, in that it displays a lower specific activity than the
      native enzyme (ALR2). Specific interactions of the bound glutathionyl moiety (GS)
      with the ALR2 active site, were predicted by a low perturbative molecular
      modelling approach. The outcoming GS allocation, involving interactions with
      residues relevant for catalysis and substrate allocation, explains the rationale
      behind the observed differences in the activity between GS-ALR2 and other thiol
      modified enzyme forms. The reversible S-glutathionylation of ALR2 observed in
      cultured intact bovine lens undergoing an oxidative/non oxidative treatment cycle
      is discussed in terms of the potential of ALR2/GS-ALR2 inter-conversion as a
      response to oxidative stress conditions.

PMID- 11306079
TI  - Effect of bovine small intestine thioredoxin on aldose reductase activity.
AB  - Under oxidative stress mediated by H(2)O(2), significant activation of purified
      aldose reductase from bovine small intestine was observed in the presence of
      purified thioredoxin from bovine small intestine.

PMID- 11306080
TI  - The role of aldose reductase in sugar cataract formation: aldose reductase plays
      a key role in lens epithelial cell death (apoptosis).
AB  - Since aldose reductase is localized primarily in lens epithelial cells, osmotic
      insults induced by the accumulation of sugar alcohols occur first in these cells.
      To determine whether the accumulation of sugar alcohols can induce lens
      epithelial cell death, galactose-induced apoptosis has been investigated in dog
      lens epithelial cells. Dog lens epithelial cells were cultured in Dulbecco's
      modified Eagle's mimimum essential medium (DMEM) supplemented with 20% fetal calf
      serum (FCS). After reaching confluence at fifth passage, the medium was replaced
      with the same DMEM medium containing 50 mM D-galactose and the cells were
      cultured for an additional 2 weeks. Almost all of the cells cultured in galactose
      medium were stained positively for apoptosis with the terminal deoxynucleotidyl
      transferance-mediated biotin-dUTP nick end labeling (TUNEL) technique. Agarose
      gel electrophoresis of these cells displayed obvious DNA fragmentation, known as
      a ladder formation. All of these apoptotic changes were absent in similar cells
      cultured in galactose medium containing 1 microM of the aldose reductase
      inhibitor AL 1576. Addition of AL 1576 also reduced the cellular galactitol
      levels from 123+/-10 microgram/10(6) cells (n=5) to 3.9+/-1.9 microgram/10(6)
      cells (n=5). These observations confirm that galactose induced apoptosis occurs
      in dog lens epithelial cells. Furthermore, the prevention of apoptosis by an
      aldose reductase inhibitor suggests that this apoptosis is linked to the
      accumulation of sugar alcohols.

PMID- 11306081
TI  - Regulation of vascular smooth muscle cell growth by aldose reductase.
AB  - Aldose reductase (AR) is a broad-specificity aldo-keto reductase with wide
      species and tissue distribution. The enzyme has been implicated in the
      development of pleiotropic complications of long-term diabetes. However, the
      euglycemic function of the enzyme remains unclear. To examine its potential role
      in cell growth, changes in AR mRNA and protein were measured in human aortic
      smooth muscle cells exposed in culture to serum or thrombin. Stimulation by these
      mitogens led to an increase in the abundance of AR mRNA and protein. Furthermore,
      inhibition of the AR by tolrestat and sorbinil diminished DNA synthesis and cell
      proliferation in response to serum. Immunohistochemical staining with anti-AR
      antibodies revealed no significant expression of AR in the smooth muscle cells of
      rat carotid arteries. However, 10 and 21 days after balloon injury, intense
      staining was associated with the proliferating cells of the neointima. Treatment
      of these animals with 40 mg/kg/day sorbinil diminished the ratio of neointima to
      the media. Together, these observations suggest that, in vascular smooth muscle
      cells (VSMC), AR is a growth-responsive gene product and that inhibition of AR
      prevents VSMC growth and decreases intimal hyperplasia and restenosis.

PMID- 11306082
TI  - Molecular mechanisms of estrogen recognition and 17-keto reduction by human
      17beta-hydroxysteroid dehydrogenase 1.
AB  - The reduction of inactive estrone (E1) to the active estrogen 17beta-estradiol
      (E2) is catalyzed by type 1 17beta-hydroxysteroid dehydrogenase (17HSD1).
      Crystallographic studies, modeling and activity measurement of mutants and
      chimeric enzymes have led to the understanding of its mechanism of action and the
      molecular basis for the estrogenic specificity. An electrophilic attack on the
      C17-keto oxygen by the Tyr 155 hydroxyl is proposed for initiation of the
      transition state. The active site is a hydrophobic pocket with catalytic residues
      at one end and the recognition machinery on the other. Tyr 155, Lys 159 and Ser
      142 are essential for the activity. The presence of certain other amino acids
      near the substrate recognition end of the active site including His 152 and Pro
      187 is critical to the shape complementarity of estrogenic ligands. His 221 and
      Glu 282 form hydrogen bonds with 3-hydroxyl of the aromatic A-ring of the ligand.
      This mechanism of recognition of E1 by 17HSD1 is similar to that of E2 by
      estrogen receptor alpha. In a ternary complex with NADP(+) and equilin, an equine
      estrogen with C7=C8 double bond, the orientation of C17=O of equilin relative to
      the C4-hydride is more acute than the near normal approach of the hydride for the
      substrate. In the apo-enzyme structure, a substrate-entry loop (residues 186-201)
      is in an open conformation. The loop is closed in this complex and Phe 192 and
      Met 193 make contacts with the ligand. Residues of the entry loop could be
      partially responsible for the estrogenic specificity.

PMID- 11306083
TI  - The crystal structure of an aldehyde reductase Y50F mutant-NADP complex and its
      implications for substrate binding.
AB  - In order to understand more fully the structural features of aldo-keto reductases
      (AKRs) that determine their substrate specificities it would be desirable to
      obtain crystal structures of an AKR with a substrate at the active site.
      Unfortunately the reaction mechanism does not allow a binary complex between
      enzyme and substrate and to date ternary complexes of enzyme, NADP(H) and
      substrate or product have not been achieved. Previous crystal structures, in
      conjunction with numerous kinetic and theoretical analyses, have led to the
      general acceptance of the active site tyrosine as the general acid-base catalytic
      residue in the enzyme. This view is supported by the generation of an
      enzymatically inactive site-directed mutant (tyrosine-48 to phenylalanine) in
      human aldose reductase [AKR1B1]. However, crystallization of this mutant was
      unsuccessful. We have attempted to generate a trapped cofactor/substrate complex
      in pig aldehyde reductase [AKR1A2] using a tyrosine 50 to phenylalanine site
      directed mutant. We have been successful in the generation of the first high
      resolution binary AKR-Y50F:NADP(H) crystal structure, but we were unable to
      generate any ternary complexes. The binary complex was refined to 2.2A and shows
      a clear lack of density due to the missing hydroxyl group. Other residues in the
      active site are not significantly perturbed when compared to other available
      reductase structures. The mutant binds cofactor (both oxidized and reduced) more
      tightly but shows a complete lack of binding of the aldehyde reductase inhibitor
      barbitone as determined by fluorescence titrations. Attempts at substrate
      addition to the active site, either by cocrystallization or by soaking, were all
      unsuccessful using pyridine-3-aldehyde, 4-carboxybenzaldehyde, succinic
      semialdehyde, methylglyoxal, and other substrates. The lack of ternary complex
      formation, combined with the significant differences in the binding of barbitone
      provides some experimental proof of the proposal that the hydroxyl group on the
      active site tyrosine is essential for substrate binding in addition to its major
      role in catalysis. We propose that the initial event in catalysis is the binding
      of the oxygen moiety of the carbonyl-group of the substrate through hydrogen
      bonding to the tyrosine hydroxyl group.

PMID- 11306084
TI  - Engineering steroid hormone specificity into aldo-keto reductases.
AB  - Steroid hormone transforming aldo-keto reductases (AKRs) include virtually all
      mammalian 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs), 20alpha-HSDs, as
      well as the 5beta-reductases. To elucidate the molecular determinants of steroid
      hormone recognition we used rat liver 3alpha-HSD (AKR1C9) as a starting structure
      to engineer either 5beta-reductase or 20alpha-HSD activity. 5beta-Reductase
      activity was introduced by a single point mutation in which the conserved
      catalytic His (H117) was mutated to Glu117. The H117E mutant had a k(cat)
      comparable to that for homogeneous rat and human liver 5beta-reductases. pH
      versus k(cat) profiles show that this mutation increases the acidity of the
      catalytic general acid Tyr55. It is proposed that the increased TyrOH(2)(+)
      character facilitates enolization of the Delta(4)-3-ketosteroid and subsequent
      hydride transfer to C5. Since 5beta-reductase precedes 3alpha-HSD in steroid
      hormone metabolism it is likely that this metabolic pathway arose by gene
      duplication and point mutation. 3alpha-HSD is positional and stereospecific for 3
      ketosteroids and inactivates androgens. The enzyme was converted to a robust
      20alpha-HSD, which is positional and stereospecific for 20-ketosteroids and
      inactivates progesterone, by the generation of loop-chimeras. The shift in
      log(10)(k(cat)/K(m)) from androgens to progestins was of the order of 10(11).
      This represents a rare example of how steroid hormone specificity can be changed
      at the enzyme level. Protein engineering with predicted outcomes demonstrates
      that the molecular determinants of steroid hormone recognition in AKRs will be
      ultimately rationalized.

PMID- 11306085
TI  - Functional genomic studies of aldo-keto reductases.
AB  - Aldose reductase (AR) is considered a potential mediator of diabetic
      complications and is a drug target for inhibitors of diabetic retinopathy and
      neuropathy in clinical trials. However, the physiological role of this enzyme
      still has not been established. Since effective inhibition of diabetic
      complications will require early intervention, it is important to delineate
      whether AR fulfills a physiological role that cannot be compensated by an
      alternate aldo-keto reductase. Functional genomics provides a variety of powerful
      new tools to probe the physiological roles of individual genes, especially those
      comprising gene families. Several eucaryotic genomes have been sequenced and
      annotated, including yeast, nematode and fly. To probe the function of AR, we
      have chosen to utilize the budding yeast Saccharomyces cerevisiae as a potential
      model system. Unlike Caenorhabditis elegans and D. melanogaster, yeast provides a
      more desirable system for our studies because its genome is manipulated more
      readily and is able to sustain multiple gene deletions in the presence of either
      drug or auxotrophic selectable markers. Using BLAST searches against the human AR
      gene sequence, we identified six genes in the complete S. cerevisiae genome with
      strong homology to AR. In all cases, amino acids thought to play important
      catalytic roles in human AR are conserved in the yeast AR-like genes. All six
      yeast AR-like open reading frames (ORFs) have been cloned into plasmid expression
      vectors. Substrate and AR inhibitor specificities have been surveyed on four of
      the enzyme forms to identify, which are the most functionally similar to human
      AR. Our data reveal that two of the enzymes (YDR368Wp and YHR104Wp) are notable
      for their similarity to human AR in terms of activity with aldoses and
      substituted aromatic aldehydes. Ongoing studies are aimed at characterizing the
      phenotypes of yeast strains containing single and multiple knockouts of the AR
      like genes.

PMID- 11306086
TI  - Three aldo-keto reductases of the yeast Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is an industrially important yeast, which is also used
      extensively as a model eukaryote. The S. cerevisiae genome has been sequenced in
      its entirety and therefore represents an ideal organism in which to carry out
      functional analysis of genes. We have identified several open reading frames in
      the S. cerevisiae genome which show significant similarity to members of the aldo
      keto reductase superfamily. The physiological roles of these gene products have
      not been previously determined, but their similarity to other enzymes suggests
      they may perform roles in carbohydrate metabolism and detoxification pathways.
      Cloning and expression of three of these enzymes has allowed their substrate
      specificities to be determined. Expression profiling and gene disruption analysis
      will allow potential roles for these enzymes within the cell to be examined.

PMID- 11306087
TI  - Forms and functions of human SDR enzymes.
AB  - Short-chain dehydrogenases/reductases (SDR) are defined by distinct, common
      sequence motifs but constitute a functionally heterogenous superfamily of
      enzymes. At present, well over 1600 members from all forms of life are annotated
      in databases. Using the defined sequence motifs as queries, 37 distinct human
      members of the SDR family can be retrieved. The functional assignments of these
      forms fall minimally into three main groups, enzymes involved in intermediary
      metabolism, enzymes participating in lipid hormone and mediator metabolism, and
      open reading frames (ORFs) of yet undeciphered function. This overview, prepared
      just before completion of the human genome project, gives the different human SDR
      forms and relates them to human diseases.

PMID- 11306088
TI  - 3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas
      testosteroni: biological significance, three-dimensional structure and gene
      regulation.
AB  - 3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) catalyses
      the oxidoreduction at carbon 3 of steroid hormones and is postulated to initiate
      the complete mineralisation of the steroid nucleus to CO(2) and H(2)O in
      Comamonas testosteroni. The enzyme was found to be functional towards a variety
      of steroid substrates, including the steroid antibiotic fusidic acid. The enzyme
      also catalyses the carbonyl reduction of non-steroidal aldehydes and ketones such
      as a novel insecticide. It is suggested that 3alpha-HSD/CR contributes to
      important defense strategies of C. testosteroni against natural and synthetic
      toxicants. The 3alpha-HSD/CR gene (hsdA) is 774 base pairs long and the deduced
      amino acid sequence comprises 258 residues with a calculated molecular mass of
      26.4 kDa. A homology search revealed 3alpha-HSD/CR as a new member of the short
      chain dehydrogenase/reductase (SDR) superfamily. Upon gel permeation
      chromatography the purified enzyme elutes as a 49.4 kDa protein indicating a
      dimeric nature of 3alpha-HSD/CR. The protein was crystallised and the structure
      solved by X-ray analysis. The crystal structure reveals one homodimer per
      asymmetric unit, thereby verifying its dimeric nature. Dimerisation takes place
      via an interface essentially built-up by helix alphaG and strand betaG of each
      subunit. So far, this type of intermolecular contact has exclusively been
      observed in homotetrameric SDRs, but never in the structure of a homodimeric SDR.
      The formation of a tetramer is blocked in 3alpha-HSD/CR by the presence of a
      predominantly alpha-helical subdomain, which is missing in all other SDRs of
      known structure. The promoter domain was localised within the 93 bp region
      upstream of hsdA and the transcriptional start site was identified at 28 bp
      upstream of the translation start site. Interestingly, hsdA expression was found
      to be under negative control by two repressor proteins, the genes of which were
      found in opposite direction downstream or overlapping with hsdA. Based on our
      results, we propose that induction of hsdA expression in C. testosteroni by
      steroids actually appears to be a de-repression by preventing the binding of
      repressor proteins to regulatory regions.

PMID- 11306089
TI  - A model on the regulation of 3alpha-hydroxysteroid dehydrogenase/carbonyl
      reductase expression in Comamonas testosteroni.
AB  - 3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) from
      Comamonas testosteroni is a key enzyme involved in the degradation of steroids
      and xenobiotic carbonyl compounds. The enzyme has recently been cloned and
      characterized by our group. A strong induction of enzyme activity is observed in
      the presence of steroids like testosterone. In the present investigation, two
      repressor proteins (Rep1 and Rep2) containing 78 and 420 amino acids,
      respectively, were found to regulate 3alpha-HSD/CR gene (hsdA) expression. Gel
      shift experiments showed that Rep2 binds to a 10 nucleotide sequence 9 bp
      upstream of the hsdA promoter. The deletion of this cis-regulating sequence
      significantly increases hsdA expression. About 1633 bp further upstream, a second
      ten nucleotide sequence, complementary to the first one, was found, which is also
      recognized by Rep2 and increases hsdA expression, if deleted. To purify the
      repressor proteins, the genes encoding each were cloned into His-tag expression
      vectors and overexpressed in Escherichia coli. Rep1 does not bind to DNA but may
      bind to 3alpha-HSD/CR mRNA as predicted by its secondary structure. Concluding
      from our data, induction of 3alpha-HSD/CR in C. testosteroni by steroids in fact
      appears to be a de-repression, where the steroidal 'inducer' prevents the binding
      of the two repressor proteins to the hsdA promoter and mRNA, respectively.

PMID- 11306090
TI  - Characterization of enzymes participating in carbonyl reduction of 4
      methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human placenta.
AB  - 4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) has been identified as one of
      the strongest nitrosamine carcinogens in tobacco products in all species tested.
      Carbonyl reduction to 4-methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL) followed
      by glucuronosylation is considered to be the main detoxification pathway in
      humans. In previous investigations, we have identified a microsomal NNK carbonyl
      reductase as being identical to 11beta-hydroxysteroid dehydrogenase 1, a member
      of the short-chain dehydrogenase/reductase (SDR) superfamily. Recently, we
      provided evidence that carbonyl reduction of NNK does also take place in cytosol
      from mouse and human liver and lung. In human liver cytosol, carbonyl reductase,
      a SDR enzyme, and AKR1C1, AKR1C2 and AKR1C4 from the aldo-keto reductase (AKR)
      superfamily were demonstrated to be responsible for NNK reduction. Since NNK
      and/or its metabolites can diffuse through the placenta and reach fetal tissues,
      we now investigated NNK carbonyl reduction in the cytosolic fraction of human
      placenta in addition to that in microsomes. Concluding from the sensitivity to
      menadione, ethacrynic acid, rutin and quercitrin as specific inhibitors, mainly
      carbonyl reductase (EC 1.1.1.184) seems to perform this reaction in human
      placenta cytosol. The presence of carbonyl reductase was confirmed by RT-PCR.
      This is the first report to provide evidence that NNAL formation in placenta is
      mediated by carbonyl reductase.

PMID- 11306091
TI  - Human 11beta-hydroxysteroid dehydrogenase 1/carbonyl reductase: additional
      domains for membrane attachment?
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) is a membrane
      integrated glycoprotein, which physiologically performs the interconversion of
      active and inactive glucocorticoid hormones and which also participates in
      xenobiotic carbonyl compound detoxification. Since 11beta-HSD 1 is fixed to the
      endoplasmic reticulum (ER) with a N-terminal membrane spanning domain, the enzyme
      is very difficult to purify in an active state. Upon expression experiments in
      Escherichia coli, 11beta-HSD 1 turns out to be hardly soluble without detergents.
      This study describes attempts to increase the solubility of 11beta-HSD 1 via
      mutagenesis experiments by generating several truncated forms expressed in E.
      coli and the yeast Pichia pastoris. Furthermore, we investigated if the codon for
      methionine 31 in human 11beta-HSD 1 could serve as an alternative start codon,
      thereby leading to a soluble form of the enzyme, which lacks the membrane
      spanning segment. Our results show that deletion of the hydrophobic membrane
      spanning domain did not alter the solubility of the enzyme. In contrast, the
      enzyme remained bound to the ER membrane even without the N-terminal membrane
      anchor. However, activity could not be found, neither with the truncated protein
      expressed in E. coli nor with that expressed in P. pastoris. Hydrophobicity plots
      proved the hydrophobic nature of 11beta-HSD 1 and indicated the existence of
      additional membrane attachment sites within its primary structure.

PMID- 11306093
TI  - Identity of dimeric dihydrodiol dehydrogenase as NADP(+)-dependent D-xylose
      dehydrogenase in pig liver.
AB  - Dimeric dihydrodiol dehydrogenases (DDs, EC 1.3.1.20), which oxidize trans
      dihydrodiols of aromatic hydrocarbons to the corresponding catechols, have been
      molecularly cloned from human intestine, monkey kidney, pig liver, dog liver, and
      rabbit lens. A comparison of the sequences with the DNA sequences in databases
      suggested that dimeric DDs constitute a novel protein family with 20 gene
      products. In addition, it was found that dimeric DD oxidizes several pentoses and
      hexoses, and the specificity resembles that of NADP(+)-dependent D-xylose
      dehydrogenase (EC 1.1.1.179) of pig liver. The inhibition of D-xylose
      dehydrogenase activity in the extracts of monkey kidney, dog liver and pig liver,
      its co-purification with dimeric DD activity from pig liver, and kinetic analysis
      of the D-xylose reduction by pig dimeric DD indicated that the two enzymes are
      the same protein.

PMID- 11306092
TI  - Expression and NNK reducing activities of carbonyl reductase and 11beta
      hydroxysteroid dehydrogenase type 1 in human lung.
AB  - The tobacco specific nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone
      (NNK), which is found in high amounts in tobacco products, is believed to play an
      important role in lung cancer induction in smokers. NNK requires metabolic
      activation by cytochrome P450 mediated alpha-hydroxylation to exhibit its
      carcinogenic properties. On the other hand, NNK is inactivated by carbonyl
      reduction to its alcohol-equivalent 4-methylnitrosamino-1-(3-pyridyl)-1-butanol
      (NNAL) followed by glucuronidation and final excretion into urine or bile.
      Carbonyl reduction and alpha-hydroxylation are the predominant pathways in man,
      and it has been postulated that the extent of these competing pathways determines
      the individual susceptibility to lung cancer. Moreover, only a minor part of all
      habitual smokers develop lung cancer, suggesting the existence of susceptibility
      genes. Microsomal 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) (EC
      1.1.1.146) and cytosolic carbonyl reductase (CR) (EC 1.1.1.184) have been shown
      to be mainly responsible for NNAL formation in liver and lung. In the present
      study, we performed comparative investigations of human lung tissue samples from
      several patients with respect to the expression and activity of 11beta-HSD 1 and
      carbonyl reductase. We observed varying levels in 11beta-HSD 1 and carbonyl
      reductase expression in these patients, as revealed by RT-PCR and ELISA. Also,
      the tissue samples showed a different activity and inhibitor profile for both
      enzymes. According to our results, variations in the expression and activity of
      NNK carbonyl reducing enzymes may constitute a major determinant in the overall
      NNK detoxification capacity and thus may be linked to the great differences
      observed in the individual susceptibility of tobacco-smoke related lung cancer.

PMID- 11306094
TI  - New developments in our understanding of the beta-hydroxyacid dehydrogenases.
AB  - The beta-hydroxyacid dehydrogenases are a structurally conserved family of
      enzymes that catalyze the NAD(+) or NADP(+)-dependent oxidation of specific beta
      hydroxyacid substrates like beta-hydroxyisobutyrate. These enzymes share distinct
      domains of amino acid sequence homology, most of which now have assigned putative
      functions. 6-phosphogluconate dehydrogenase and beta-hydroxyisobutyrate
      dehydrogenase, the most well-characterized members, both appear to be readily
      inactivated by chemical modifiers of lysine residues, such as 2,4,6
      trinitrobenzene sulfonate (TNBS). Peptide mapping by ESI-LCMS showed that
      inactivation of beta-hydroxyisobutyrate dehydrogenase with TNBS occurs with the
      labeling of a single lysine residue, K248. This lysine residue is completely
      conserved in all family members and may have structural importance relating to
      cofactor binding. The structural framework of the beta-hydroxyacid dehydrogenase
      family is shared by many bacterial homologues. One such homologue from E. coli
      has been cloned and expressed as recombinant protein. This protein was found to
      have enzymatic activity characteristic of tartronate semialdehyde reductase, an
      enzyme required for bacterial biosynthesis of D-glycerate. A homologue from H.
      influenzae was also cloned and expressed as recombinant protein. This protein was
      active in the oxidation of D-glycerate, but showed approximately ten-fold higher
      activity with four carbon substrates like beta-D-hydroxybutyrate and D-threonine.
      This enzyme might function in H. influenzae, and other species, in the
      utilization of polyhydroxybutyrates, an energy storage form specific to bacteria.
      Cloning and characterization of these bacterial beta-hydroxyacid dehydrogenases
      extends our knowledge of this enzyme family.

PMID- 11306095
TI  - 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus:
      structural and functional aspects.
AB  - 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) activity has been described in
      all filamentous fungi tested, but until now only one 17beta-HSD from Cochliobolus
      lunatus (17beta-HSDcl) was sequenced. We examined the evolutionary relationship
      among 17beta-HSDcl, fungal reductases, versicolorin reductase (Ver1),
      trihydroxynaphthalene reductase (THNR), and other homologous proteins. In the
      phylogenetic tree 17beta-HSDcl formed a separate branch with Ver1, while THNRs
      reside in another branch, indicating that 17beta-HSDcl could have similar
      function as Ver1. The structural relationship was investigated by comparing a
      model structure of 17beta-HSDcl to several known crystal structures of the short
      chain dehydrogenase/reductase (SDR) family. A similarity was observed to
      structures of bacterial 7alpha-HSD and plant tropinone reductase (TR).
      Additionally, substrate specificity revealed that among the substrates tested the
      17beta-HSDcl preferentially catalyzed reductions of steroid substrates with a 3
      keto group, Delta(4) or 5alpha, such as: 4-estrene-3,17-dione and 5alpha
      androstane-3,17-dione.

PMID- 11306096
TI  - Novel enzymological profiles of human 11beta-hydroxysteroid dehydrogenase type 1.
AB  - The human enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) catalyzes the
      reversible oxidoreduction of 11beta-OH/11-oxo groups of glucocorticoid hormones.
      Besides this important endocrinological property, the type 1 isozyme (11beta
      HSD1) mediates reductive phase I reactions of several carbonyl group bearing
      xenobiotics, including drugs, insecticides and carcinogens. The aim of this study
      was to explore novel substrate specificities of human 11beta-HSD1, using
      heterologously expressed protein in the yeast system Pichia pastoris. In addition
      to established phase I xenobiotic substrates, it is now demonstrated that
      transformed yeast strains catalyze the reduction of ketoprofen to its hydroxy
      metabolite, and the oxidation of the prodrug DFU-lactol to the pharmacologically
      active lactone compound. Purified recombinant 11beta-HSD1 mediated oxidative
      reactions, however, the labile reductive activity component could not be
      maintained. In conclusion, evidence is provided that human 11beta-HSD1 in vitro
      is involved in phase I reactions of anti-inflammatory non-steroidal drugs like
      ketoprofen and DFU-lactol.

PMID- 11306097
TI  - Metabolic activation of polycyclic aromatic hydrocarbon trans-dihydrodiols by
      ubiquitously expressed aldehyde reductase (AKR1A1).
AB  - Polycyclic aromatic hydrocarbons (PAHs) are metabolized to trans-dihydrodiol
      proximate carcinogens by CYP1A1 and epoxide hydrolase (EH). CYP1A1 or aldo-keto
      reductases (AKRs) from the 1C subfamily can further activate the trans
      dihydrodiols by forming either anti-diol-epoxides or reactive and redox active o
      quinones, respectively. To determine whether other AKR superfamily members can
      divert trans-dihydrodiols to o-quinones, the cDNA encoding human aldehyde
      reductase (AKR1A1) was isolated from hepatoma HepG2 cells using RT-PCR, subcloned
      into a prokaryotic expression vector, overexpressed in E. coli and purified to
      homogeneity in milligram amounts. Studies revealed that AKR1A1 preferentially
      oxidized the metabolically relevant (-)-[3R,4R]-dihydroxy-3,4
      dihydrobenz[a]anthracene. AKR1A1 also displayed high utilization ratios
      (V(max)/K(m)) for the following PAH trans-dihydrodiols: (+/-)trans-3,4-dihydroxy
      3,4-dihydro-7-methylbenz[a]anthracene, (+/-)trans-3,4-dihydroxy-3,4-dihydro-7,12
      dimethylbenz[a]anthracene and (+/-)trans-7,8-dihydroxy-7,8-dihydro-5
      methylchrysene. Multiple tissue expression (MTE) arrays were used to measure the
      co-expressed of CYP1A1, EH and AKR1A1. All the three enzymes co-expressed to
      sites of PAH activation. The high catalytic efficiency of AKR1A1 for potent
      proximate carcinogen trans-dihydrodiols and its presence in tissues that contain
      CYP1A1 and EH suggests that it plays an important role in this alternative
      pathway of PAH activation (supported by CA39504).

PMID- 11306098
TI  - Role of the conserved Ser-Tyr-Lys triad of the SDR family in sepiapterin
      reductase.
AB  - Sepiapterin reductase (EC 1.1.1.153; SPR) is an enzyme involved in the
      biosynthesis of tetrahydrobiopterin; and SPR has been identified as a member of
      the NADP(H)-preferring short-chain dehydrogenase/reductase (SDR) family based on
      its catalytic properties for exogenous carbonyl compounds and molecular
      structure. To examine possible differences in the catalytic sites of SPR for
      exogenous carbonyl compounds and the native pteridine substrates, we investigated
      by site-directed mutagenesis the role of the highly conserved Ser-Tyr-Lys triad
      (Ser and YXXXK motif) in SPR, which was shown to be the catalytic site of SDR
      family enzymes. From the analysis of catalytic constants for single- and double
      point mutants against the triad, Ser and YXXXK motif, in the SPR molecule,
      participate in the reduction of the carbonyl group of both pteridine and
      exogenous carbonyl compounds. The Ser and the Tyr of the triad may co-act in
      proton transfer and stabilization for the carbonyl group of substrates, as was
      demonstrated for those in the SDR family. But either the Tyr or the Ser of SPR
      can function alone for proton transfer to a certain extent and show low activity
      for both substrates.

PMID- 11306099
TI  - Site-directed mutagenesis studies of bovine liver cytosolic dihydrodiol
      dehydrogenase: the role of Asp-50, Tyr-55, Lys-84, His-117, Cys-145 and Cys-193
      in enzymatic activity.
AB  - A previous report on the cloning, bacterial expression and purification of bovine
      liver cytosolic dihydrodiol dehydrogenase (DD3) cDNA (1,330 bp in full length)
      using pKK223-3 expression vector characterize the properties of the recombinant
      DD3 in the aspects of substrate specificity and inhibitor sensitivity (Terada et
      al., Adv. Exp. Biol. Res. 414 (1997) 543-53). The nucleotide sequence of this DD3
      cDNA completely matches that of bovine liver-type prostaglandin F synthase (PGFS)
      (Suzuki et al., J. Biol. Chem. 274 (1999) 241-8). In the present study, a large
      amount of recombinant DD3 (rDD3) was expressed in Escherichia coli BL21 (DE3)
      with a pET28a expression vector. The recombinant DD3 (rDD3) was easily and
      quickly purified to an apparent homogeneity with one step column chromatography
      of Ni(2+)-affinity resin. The rDD3 showed essentially the same substrate
      specificity and inhibitor sensitivity as purified liver DD3 (DD3). To analyze the
      role of amino acid residues of DD3 in its enzymatic activity, site-directed
      mutagenesis of DD3 with PCR method was performed. The results of the analyses of
      these mutants in the aspects of substrate specificity and cofactor-binding
      suggested a variety of functions in the enzymatic activity: as an active site Tyr
      55 may act as a general acid and Asp-50, Lys-84 and His-117 may play an important
      role in the control of protonation of Tyr-55 as a general acid in the
      dehydrogenase activity under higher pH conditions, though these residues may not
      be involved in reductase activity under lower pH conditions. Though the mutated
      DD3s (Cys to Ser) did not show significant differences in their substrate
      specificities, these mutants showed different sensitivities to SH-reagents.
      Present results indicate that Cys-193 may play an important role in the
      modulation of enzymatic activity under redox conditions generated with GSH+GSSG
      among five cysteines in DD3.

PMID- 11306100
TI  - Characterization of multiple Chinese hamster carbonyl reductases.
AB  - Carbonyl reductase (CR) is an enzyme which can catalyze the oxidoreduction of
      various carbonyl compounds in the presence of NAD(P)H. With the PCR method, using
      primers carrying the conserved nucleotide sequence among mammalian CRs, we
      isolated three different cDNAs (CHCR1, CHCR2 and CHCR3) which encode a unique
      carbonyl reductase from the Chinese hamster. The PCR products of CHCR1 and CHCR2
      were clearly isolated with Bpu1102I, BspEI and XmaI restriction enzymes. The
      nucleotide-sequence of CHCR3 was completely different from those of CHCR1 and
      CHCR2. The predicted double-wound betaalphabetaalpha-structures of the CHCRs
      suggests the presence of a typical NADP(+)-binding motif and is similar to the
      corresponding region of 3alpha,20beta-hydroxysteroid dehydrogenase and mouse lung
      tetrameric carbonyl reductase. The deduced amino acid sequence of CHCR1 showed a
      high homology to CHCR2 (>96%) and the other mammalian CRs (>81%). However, CHCR3
      showed a high homology to human CBR3 (>86%) and a relatively lower homology to
      the other CHCRs (<76%). Bacterial recombinant CHCRs showed typical carbonyl
      reductase activities towards 4-benzoylpyridine, 4-nitrobenzaldehyde and pyridine
      4-carboxyaldehyde. These three CRs showed not only 3-keto reductase of steroids,
      but also 20-keto reductase. However, these CRs did not show any activity of 17
      keto reductase activity. Both CHCR1 and CHCR2 have prostaglandin 9-keto reductase
      and 15-hydroxyprostaglandin dehydrogenase activities towards PGE(2) and
      PGF(2alpha) from the analyses of enzymatic reaction products. The results of
      Western blotting and RT-PCR suggest these CHCRs have a tissue-dependent
      distribution in the Chinese hamster.

PMID- 11306101
TI  - Cloning and expression of cDNA encoding hamster liver 3
      hydroxyhexobarbital/17beta(3alpha)-hydroxysteroid dehydrogenase 1.
AB  - Using RACE techniques we have cloned and sequenced one of the hamster liver 3
      hydroxy-hexobarbital dehydrogenases which catalyze not only cyclic alcohols but
      also 17beta-hydroxy-steroids and 3alpha-hydroxysteroids. The gene specific
      primers to 3-hydroxyhexobarbital dehydrogenase 1 (G2) were synthesized on the
      basis of its partial peptide sequences. The sequence of full length cDNA
      generated by 3'- and 5'-RACE PCR consisted of 1225 nucleotides including an open
      reading frame of 972 nucleotides encoding a protein of 323 amino acids. The
      deduced amino acid sequence matched exactly with the partial peptide sequences of
      hamster liver 3-hydroxyhexobarbital dehydrogenase 1 (G2). The sequence showed
      84.5% identity to mouse liver 17beta-dehydrogenase(A-specific), and 74-76%
      identity to human liver bile acid binding protein/3alpha-hydroxysteroid
      dehydrogenase (DD2), human liver 3alpha-hydroxysteroid dehydrogenase type I (DD4)
      and type II (DD3), and rabbit ovary 20alpha-hydroxysteroid dehydrogenase. The
      protein contains catalytic residues of aldo-keto reductases, Asp50, Tyr55, Lys84,
      His117. These results suggest that the hamster liver 3
      hydroxyhexobarbital/17beta(3alpha)-hydroxysteroid dehydrogenase belongs to aldo
      keto reductase superfamily. The insert containing the full-length cDNA of 3
      hydroxyhexobarbital dehydrogenase and vector specific overhang produced by PCR
      was annealed with pET-32 Xa/LIC vector. The plasmid was transformed into BL21
      (DE3) cells containing pLysS. The recombinant enzyme was induced 1 mM IPTG. The
      expressed enzyme was produced as fusion protein and purified by nickel chelating
      affinity chromatography followed by POROS CM column chromatography and superdex
      75 gel filtration. Molecular weight of the recombinant enzyme fused thioredoxin
      and his*tag was about 55000 and that was 35000 after Factor Xa protease
      treatment. The recombinant enzyme dehydrogenated 3-hydroxy-hexobarbital, 1
      acenaphthenol, 2-cyclohexen-1-ol, testosterone, glycolithocholic acid as well as
      the native enzyme purified from hamster liver.

PMID- 11306102
TI  - Coenzyme specificity of human monomeric carbonyl reductase: contribution of Lys
      15, Ala-37 and Arg-38.
AB  - Short-chain dehydrogenases/reductases catalyze the oxidoreduction of alcohol and
      carbonyl compounds using either NAD or NADPH as coenzyme. Structural analysis
      suggests that specificity for NADPH is conferred by two highly conserved basic
      residues in the N-terminal part of the peptide chain, whereas specificity for NAD
      correlates with the presence of an Asp adjacent to the position of the distal
      basic residue in NADP-dependent enzymes. We carried out site-directed mutagenesis
      of the two basic residues: Lys-15 and Arg-38, as well as of Ala-37 of human
      monomeric carbonyl reductase in order to investigate their contribution to
      coenzyme binding and specificity. Substitution of Lys-15 or Arg-38 by Gln and,
      even more pronounced Asp decreased the catalytic efficiency (k(cat)/K(m,NADPH))
      by more than three orders of magnitude. Similarly, substitution of Asp for Ala-37
      decreased k(cat)/K(m,NADPH) 1000-fold but had little effect on k(cat)/K(m,NADH).
      The results demonstrate the importance of basic residues at positions 15 and 38
      and the absence of an acidic residue at position 37 for NADPH binding and
      catalysis.

PMID- 11306103
TI  - Molecular cloning, expression and tissue distribution of hamster diacetyl
      reductase. Identity with L-xylulose reductase.
AB  - Using rapid amplification of cDNA ends PCR, a cDNA species for diacetyl reductase
      (EC 1.1.1.5) was isolated from hamster liver. The encoded protein consisted of
      244 amino acids, and showed high sequence identity to mouse lung carbonyl
      reductase and hamster sperm P26h protein, which belong to the short-chain
      dehydrogenase/reductase family. The enzyme efficiently reduced L-xylulose as well
      as diacetyl, and slowly oxidized xylitol. The K(m) values for L-xylulose and
      xylitol were similar to those reported for L-xylulose reductase (EC 1.1.1.10) of
      guinea pig liver. The identity of diacetyl reductase with L-xylulose reductase
      was demonstrated by co-purification of the two enzyme activities from hamster
      liver and their proportional distribution in other tissues.

PMID- 11306104
TI  - Enzyme regulation by reversible zinc inhibition: glycerol phosphate dehydrogenase
      as an example.
AB  - Since cellular zinc is not freely available as the inorganic ion, zinc proteins
      must acquire their metal from some other source. But how, when, and where they
      acquire it is unknown. Metallothionein can participate in the controlled delivery
      of zinc by binding it with high stability and by mobilizing it through a novel
      biochemical mechanism that critically depends on the redox activity of the zinc
      sulfur bond. Thus, metallothionein activates zinc-depleted alcohol (sorbitol)
      dehydrogenases by glutathione-modulated zinc transfer. In addition to its
      catalytic, co-catalytic, and/or structural roles in a myriad of enzymes, zinc
      also inhibits some enzymes that are not necessarily zinc enzymes, e.g.
      glyceraldehyde and glycerol phosphate dehydrogenases, and aldehyde dehydrogenase.
      Zinc inhibits glycerol phosphate dehydrogenase with an IC(50) value of 100 nM.
      Zinc binding is slow at low pH, but instantaneous at high pH. Thionein, the
      apoprotein of metallothionein, re-activates the zinc-inhibited enzyme. Tight
      inhibition by zinc and activation of glycerol phosphate dehydrogenase by
      thionein, a biological chelating agent, provide further support that modulation
      of zinc binding by metallothionein and thionein is a physiological mechanism of
      enzyme regulation. Since glycerol phosphate dehydrogenase is a key enzyme in
      energy metabolism, the effect of zinc is expected to elicit significant
      physiological responses.

PMID- 11306105
TI  - Physiological functions and hormonal regulation of mouse vas deferens protein
      (AKR1B7) in steroidogenic tissues.
AB  - The MVDP (mouse vas deferens protein) gene encodes an aldose reductase-like
      protein (AKR1B7) highly expressed in vas deferens epithelium and zona fasciculata
      of the adrenal cortex. Recombinant MVDP showed kinetic properties distinct from
      those of aldose reductase, including its spectrum of substrates, cofactor
      preference and sensitivity to inhibitors. We demonstrate that in adrenocortical
      cells, MVDP, rather than aldose reductase, is the principal reductase for
      isocaproaldehyde (a product of side-chain cleavage of cholesterol) and 4
      hydroxynonenal (a lipid peroxidation product). In steroidogenic tissues MVDP
      expression is regulated by pituitary trophic hormones, namely ACTH in adrenals,
      FSH in ovaries, and LH in testicular Leydig cells.

PMID- 11306106
TI  - Biogenic aldehyde(s) derived from the action of monoamine oxidase may mediate the
      antidipsotropic effect of daidzin.
AB  - Daidzin, a major active principle of an ancient herbal treatment for 'alcohol
      addiction', was first shown to suppress ethanol intake in Syrian golden hamsters.
      Since then this activity has been confirmed in Wistar rats, Fawn hooded rats,
      genetically bred alcohol preferring P rats and African green moneys under various
      experimental conditions, including two-level operant, two-bottle free-choice,
      limited access, and alcohol-deprivation paradigms. In vitro, daidzin is a potent
      and selective inhibitor of mitochondrial aldehyde dehydrogenase (ALDH-2).
      However, in vivo, it does not affect overall acetaldehyde metabolism in golden
      hamsters. Using isolated hamster liver mitochondria and 5-hydroxytryptamine (5
      HT) and dopamine (DA) as the substrates, we demonstrated that daidzin inhibits
      the second but not the first step of the MAO/ALDH-2 pathway, the major pathway
      that catalyzes monoamine metabolism in mitochondria. Correlation studies using
      structural analogs of daidzin led to the hypothesis that the mitochondrial
      MAO/ALDH-2 pathway may be the site of action of daidzin and that one or more
      biogenic aldehydes such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or DOPAL
      derived from the action of monoamine oxidase (MAO) may be mediators of its
      antidipsotropic action.

PMID- 11306107
TI  - Cytochrome P450 2E1 metabolically activates propargyl alcohol: propiolaldehyde
      induced hepatocyte cytotoxicity.
AB  - Pargyline, an antihypertensive agent and monoamine oxidase inhibitor, induces
      hepatic GSH depletion and hepatotoxicity in vivo in rats [E.G. De Master, H.W.
      Sumner, E. Kaplan, F. N. Shirota, H.T. Nagasawa, Toxicol. Appl. Pharmacol. 65
      (1982) 390-401]. Propargyl alcohol (2-propyn-1-ol), because of its structural
      similarity to allyl alcohol, was thought to be activated by alcohol
      dehydrogenase. However, it is a poor substrate compared to allyl alcohol and it
      was therefore proposed that propargyl alcohol-induced liver injury involved
      metabolic activation by catalase/H(2)O(2) [E.G. De Master, T. Dahlseid, B.
      Redfern, Chem. Res. Toxicol. 7 (1994) 414-419]. In the following we showed that;
      (1) propargyl alcohol-induced cytotoxicity was markedly enhanced in CYP 2E1
      induced hepatocytes and prevented by various CYP 2E1 inhibitors but was only
      slightly affected when alcohol dehydrogenase was inhibited with
      methylpyrazole/DMSO or when catalase was inactivated with azide or aminotriazole,
      (2) hepatocyte GSH depletion preceded cytotoxicity and was inhibited by
      cytochrome P450 inhibitors but not by catalase/alcohol dehydrogenase inhibitors.
      GSH conjugate formation during propargyl alcohol metabolism by microsomal mixed
      function oxidase in the presence of GSH was also prevented by anti-rat CYP 2E1 or
      CYP 2E1 inhibitors, (3) cytotoxicity was prevented when lipid peroxidation was
      inhibited with antioxidants, desferoxamine (ferric chelator) or dithiothreitol.
      Propargyl alcohol-induced cytotoxicity and reactive oxygen species formation were
      markedly increased in GSH-depleted hepatocytes. All of this evidence suggests
      that propargyl alcohol-induced cytotoxicity involves metabolic activation by CYP
      2E1 to form propiolaldehyde that causes hepatocyte lysis as a result of GSH
      depletion and lipid peroxidation.

PMID- 11306108
TI  - Apoptosis of PC12 cells by 4-hydroxy-2-nonenal is mediated through selective
      activation of the c-Jun N-terminal protein kinase pathway.
AB  - Cytotoxic lipid peroxides such as 4-hydroxy-2-nonenal (HNE) are produced when
      cells are exposed to toxic chemicals. However, the mechanism by which HNE induces
      cell death has been poorly understood. In this study, we investigated the
      molecular mechanism of HNE-induced apoptosis in PC12 cells by measuring the
      activities of the mitogen-activated protein (MAP) kinases involved in early
      signal transduction pathways. Within 15-30 min after HNE treatment, c-Jun N
      terminal protein kinase (JNK) was maximally activated, before returning to
      control level after 1 h post-treatment. In contrast, activities of extracellular
      signal regulated kinase (ERK) and p38 MAP kinase remained unchanged from their
      basal levels. SEK1, an upstream kinase of JNK, was also activated
      (phosphorylated) within 5 min after HNE treatment and remained activated for up
      to 60 min. Marked activation of the JNK pathway through SEK1 was demonstrated by
      the transient transfection of cDNA for wild type SEK1 and JNK into COS-7 cells.
      Furthermore, significant reductions in JNK activation and HNE-induced cell death
      were observed when the dominant negative mutant of SEK1 was co-transfected with
      JNK. Pretreatment of PC12 cells with a survival promoting agent, 8-(4
      chlorophenylthio)-cAMP, prevented both the HNE-induced JNK activation and
      apoptosis. Nonaldehyde, a nontoxic aldehyde, caused neither apoptosis nor JNK
      activation. Pretreatment of PC12 cells with SB203580, a specific inhibitor of p38
      MAP kinase, had no effect on HNE-induced apoptosis. All these data suggest that
      the HNE-mediated apoptosis of PC12 cells is likely to be mediated through the
      selective activation of the SEK1-JNK pathway without activation of ERK or p38 MAP
      kinase.

PMID- 11306109
TI  - Binding of pyridine coenzymes to the beta-subunit of the voltage sensitive
      potassium channels.
AB  - The beta-subunit of the voltage-sensitive K(+) channels shares 15-30% amino acid
      identity with the sequences of aldo-keto reductases (AKR) genes. However, the AKR
      properties of the protein remain unknown. To begin to understand its
      oxidoreductase properties, we examine the pyridine coenzyme binding activity of
      the protein in vitro. The cDNA of K(v)beta2.1 from rat brain was subcloned into a
      prokaryotic expression vector and overexpressed in Escherichia coli. The purified
      protein was tetrameric in solution as determined by size exclusion
      chromatography. The protein displayed high affinity binding to NADPH as
      determined by fluorometric titration. The K(D) values for NADPH of the full
      length wild-type protein and the N-terminus deleted protein were 0.1+/-0.007 and
      0.05+/-0.006 M, respectively - indicating that the cofactor binding domain is
      restricted to the C-terminus, and is not drastically affected by the absence of
      the N-terminus amino acids, which form the ball and chain regulating voltage
      dependent inactivation of the alpha-subunit. The protein displayed poor affinity
      for other coenzymes and the corresponding values of the K(D) for NADH and NAD
      were between 1-3 microM whereas the K(D) for FAD was >10 microM. However,
      relatively high affinity binding was observed with 3-acetyl pyridine NADP,
      indicating selective recognition of the 2' phosphate at the binding site. The
      selectivity of K(v)beta2.1 for NADPH over NADP may be significant in regulating
      the K(+) channels as a function of the cellular redox state.

PMID- 11306110
TI  - The nine-banded armadillo (Dasypus novemcinctus) is naturally infected with
      Sarcocystis neurona.
AB  - Sarcocysts were dissected from the tongue of a nine-banded armadillo (Dasypus
      novemcinctus). DNA was extracted and characterised by PCR amplification followed
      by restriction fragment length polymorphism analysis and nucleotide sequencing. A
      total of 1879 nucleotides were compared; the sarcocyst DNA sequence was identical
      to that reported for Sarcocystis neurona. DNA was extracted from the sarcocysts
      of five more nine-banded armadillos. A 254-nucleotide sequence was determined for
      each and found to be identical to S. neurona. Western blot techniques for
      detection of anti-S. neurona antibody were developed for use with armadillo
      plasma and samples from 19 wild-caught and 17 captive-raised armadillos were
      examined. Whereas all of the 19 wild-caught armadillos had antibodies to S.
      neurona, only one of 17 captive-raised armadillos did. These results suggest that
      the nine-banded armadillo are naturally infected with S. neurona.

PMID- 11306111
TI  - The nine-banded armadillo (Dasypus novemcinctus) is an intermediate host for
      Sarcocystis neurona.
AB  - The nine-banded armadillo (Dasypus novemcinctus) is an intermediate host of at
      least three species of Sarcocystis, Sarcocystis dasypi, Sarcocystis diminuta, and
      an unidentified species; however, life cycles of these species have not been
      determined. Following feeding of armadillo muscles containing sarcocysts to the
      Virginia opossum (Didelphis virginiana), the opossums shed sporulated Sarcocystis
      sporocysts in their faeces. Mean dimensions for sporocysts were 11.0x7.5 microm
      and each contained four sporozoites and a residual body. Sporocysts were
      identified as Sarcocystis neurona using PCR and DNA sequencing. A 2-month-old
      foal that was negative for S. neurona antibodies in the CSF was orally inoculated
      with 5x10(5) sporocysts. At 4 weeks post-infection, the foal had a 'low positive'
      result by immunoblot for CSF antibodies to S. neurona and by week 6 had a 'strong
      positive' CSF result and developed an abnormal gait with proprioceptive deficits
      and ataxia in all four limbs. Based on the results of this study, the nine-banded
      armadillo is an intermediate host of S. neurona.

PMID- 11306112
TI  - The effect of the acanthocephalan parasite Pomphorhynchus laevis on the lipid and
      glycogen content of its intermediate host Gammarus pulex.
AB  - Besides conspicuous changes in behaviour, manipulative parasites may also induce
      subtle physiological effects in the host that may also be favourable to the
      parasite. In particular, parasites may be able to influence the re-allocation of
      resources in their own favour. We studied the association between the presence of
      the acanthocephalan parasite, Pomphorhynchus laevis, and inter-individual
      variation in the lipid and glycogen content of its crustacean host, Gammarus
      pulex (Amphipoda). Infected gravid females had significantly lower lipid contents
      than uninfected females, but there was no difference in the lipid contents of non
      gravid females and males that were infected with P. laevis. In contrast, we found
      that all individuals that were parasitised by P. laevis had significantly
      increased glycogen contents, independent of their sex and reproductive status. We
      discuss our results in relation to sex-related reproductive strategies of hosts,
      and the influence they may have on the level of conflict over energy allocation
      between the host and the parasite.

PMID- 11306113
TI  - Male-female larval interactions in Schistosoma mansoni-infected Biomphalaria
      glabrata.
AB  - This paper investigates Schistosoma mansoni male-female larval interactions in
      simultaneous bi-miracidial Biomphalaria glabrata infections. Larval interactions
      were analysed at four levels of infection: (i), miracidial infectivity, estimated
      by the prevalence of mollusc infection; (ii), mollusc pathology, measured by the
      mollusc growth and survival; (iii), dynamics of the cercarial sex ratio; and
      (iv), cercarial infectivity, measured as the success of development into
      adulthood. Our results showed that larval interactions exist in S. mansoni
      infected B. glabrata. These interactions do not occur in miracidial infectivity,
      but occur in mollusc pathology, cercarial sex ratio dynamics and cercarial
      infectivity. Regarding mollusc pathology, we showed that the bi-miracidially
      infected molluscs were smaller than the mono-miracidially-infected ones. This
      could be the result of larval competition. Regarding the dynamics of the
      cercarial sex ratio, we showed larval female superiority as compared with male
      larvae inducing the shedding of female-biased cercarial sex ratios. These sex
      ratios were rhythmic and could be the reflection of an external expression of the
      intramolluscan development. Regarding cercarial infectivity, we showed that the
      simultaneous presence of both sexes in a mollusc increased the cercarial
      infectivity. This result could be due to male-female larval synergism.

PMID- 11306114
TI  - Characterisation of Haemonchus contortus-derived cell populations propagated in
      vitro in a tissue culture environment and their potential to induce protective
      immunity in sheep.
AB  - Cell populations derived from viable Haemonchus contortus L(3) larvae were
      propagated in vitro in a tissue culture environment for a prolonged period (>48
      months). Microscopic evaluation of H. contortus-derived cell populations revealed
      gross morphological characteristics highly analogous to those described for cell
      types originating from species of plant nematodes propagated in vitro in a tissue
      culture environment for a briefer period of time (<6 months). The
      characterisation of extracts harvested from tissue culture populations of H.
      contortus-derived cells by SDS-PAGE analysis detected molecular fractions of
      approximately 29, 45, 55, and 200-kDa that closely correlated with reports for
      preparations obtained from intact/viable H. contortus larvae. Complementary
      investigations detected the dual biochemical expression of phosphohydrolase and
      aminopeptidase-M activities based on the hydrolysis of the synthetic enzyme
      specific substrates, para-nitrophenylphosphate and leucine-para-nitroanaline,
      respectively. The identification of phosphohydrolase and aminopeptidase-M-like
      biochemical activity in fractions harvested from H. contortus-derived cell
      populations and propagated in vitro in tissue culture served as evidence
      validating their parasitic-origin. Further validation of H. contortus-derived
      cell populations propagated in tissue culture entailed the formulation of Triton
      X-100 extracts containing potential immunoprotective antigens with SEAM adjuvant
      and its administration by intramuscular injection (100 microg total protein) to
      healthy sheep (n=8) on day 0 (left rear-limb) and day +14 (right rear-limb).
      Animals on day 28 subsequently received a single oral challenge of 10,000
      infective L(3)-stage H. contortus larvae. Applying ELISA methodologies, increases
      in antigen-specific IgM and IgG were detected in ovine serum samples.
      Interpretation of experimental findings revealed that sheep with the greatest
      antigen-specific humoral immune responses (IgG titre 1/3125) also demonstrated a
      degree of reduced abomasal H. contortuslarvae burdens (60% reduction). Polyclonal
      antibody from immunoprotected sheep was subsequently found to recognise both the:
      (i), digestive tract; and (ii), antigen extracts associated with intact/viable H.
      contortus larvae. These experimental findings reveal the potential feasibility of
      propagating parasite-derived cell populations in an in vitro tissue culture
      environment in a manner that retains their ability to express immunoprotective
      antigenic fractions.

PMID- 11306115
TI  - PCR amplification of putative gpa-2 and gpa-3 orthologs from the (A+T)-rich
      genome of Strongyloides stercoralis.
AB  - Two G protein alpha subunit genes orthologous to gpa-2 and gpa-3 in
      Caenorhabditis elegans have been identified in the parasitic nematode,
      Strongyloides stercoralis. These genes mediate chemosensory signal transduction
      regulating dauer arrest in C. elegans. In the parasite, they represent candidate
      mediators for regulation of the choice between free-living and parasitic life
      cycles, the obligatory developmental arrest of infective larvae, and reactivation
      of development after infection. The (A+T) content of these genes is 72.2% for
      coding sequences, 90% for introns, and 84.1% for 5' and 3' flanking regions,
      requiring the use of low extension temperatures for long distance PCR. The
      possible significance of conserved structural motifs of these proteins is
      discussed.

PMID- 11306116
TI  - Detection of Babesia caballi and Babesia equi in Dermacentor nuttalli adult
      ticks.
AB  - Ticks play an important role in human and veterinary medicine particularly due to
      their ability to transmit protozoan pathogens. In this study we have demonstrated
      that polymerase chain reaction (PCR) and nested PCR methods enabled detection of
      Babesia caballi and Babesia equi in field isolates of Dermacentor nuttalli adult
      ticks from Mongolia. Primers specific for 218 bp fragment merozoite antigen 1
      (EMA-1) gene of B. equi successfully amplified products from all samples of D.
      nuttalli adult ticks while primers for the 430 bp fragment product from BC48 gene
      of B. caballi amplified products from seven of the 54 samples. Using PCR and
      nested PCR methods we have found mixed infections with B. equi and B. caballi in
      the tick vector. The amplified DNA fragment from D. nuttalli ticks was inserted
      into the EcoRV site of pBluescript SK and sequenced. The sequence of the 430 bp
      fragment was completely identical to the nucleotide sequence of the USDA strain
      of B. caballi. These results suggest that D. nuttalli may play an important role
      as a vector of both B. caballi and B. equi and also may be important in
      maintaining endemicity of equine piroplasmosis in Mongolia.

PMID- 11306117
TI  - Primary structure and sexual stage-specific expression of a LAMMER protein kinase
      of Plasmodium falciparum.
AB  - We have isolated a LAMMER-like gene from Plasmodium falciparum by vectorette
      technique. The gene consists of 3316 bp encoding a protein 881 amino acids with a
      predicted molecular mass of approximately 106.7 kDa. The encoded protein, termed
      PfLAMMER, is composed of two distinct domains. The N-terminal domain is not
      related to any previously described protein kinases and has several interesting
      features including multiple consensus phosphorylation sites for a range of
      protein kinases, a number of RS/SR dipeptides, a large proportion of charged
      amino acids, two putative nuclear localisation signals and 14 copies of a
      tetramer DKYD repeats. The C-terminal domain is characteristic of a kinase in the
      LAMMER family with the highest homology to the Arabidopsis thaliana AFC3 kinase.
      Genomic restriction analysis showed that PfLAMMER is encoded by a single copy
      gene in the parasite genome. A single transcript of approximately 3800
      nucleotides is expressed specifically in the sexual stage, indicating that
      PfLAMMER may be important in regulating the processes of sexual differentiation
      of the parasite.

PMID- 11306118
TI  - Phylogenetic relationships within the polyopisthocotylean monogeneans
      (Platyhelminthes) inferred from partial 28S rDNA sequences.
AB  - Recent studies based on molecular data (18S rDNA and partial 28S rDNA) and
      morphology did not resolve a terminal polytomy within the Polyopisthocotylea.
      Here, we have used sequences from the full domain D2 of the 28S rDNA for 24
      species (18 new sequences) with three phylogenetic methods, maximum parsimony,
      neighbour-joining and maximum likelihood, to infer the relationships among the
      Polyopisthocotylea. The analysis of the domain D2 of the 28S rDNA has been
      performed on two data sets. The first one, complete, included the Polystomatidae
      as the outgroup in order to infer general relationships, and the second one,
      reduced, excluded the Polystomatidae and the polyopisthocotylean parasites of
      chondrichthyans, but used the Mazocraeidae as the outgroup in order to resolve
      the relationships between the terminal groups. The topology found, sustained by
      high bootstrap and decay index value, is: (outgroup (Chimaericolidae
      (Mazocraeidae (Gastrocotylinea, other Polyopisthocotylea)))). The
      polyopisthocotylean parasites of chondrichthyans are the sister-group of the
      polyopisthocotylean parasites of teleosts. In the latter, the Mazocraeidae,
      essentially parasites of Clupeidae, have a basal position. The polytomy between
      Gastrocotylinea, Discocotylinea and Microcotylinea is partially resolved in this
      study for the first time: the Gastrocotylinea are the sister-group of an
      unresolved group including the Microcotylinea, Discocotylinea and
      Plectanocotylidae. Inclusion of the Plectanocotylidae in the suborder
      Mazocraeinea is rejected. Monophyly of the Microcotylinea and Plectanocotylidae
      is confirmed, but monophyly of the Discocotylinea is questioned by the exclusion
      of Diplozoon.

PMID- 11306119
TI  - Synonymous codon usage in Cryptosporidium parvum: identification of two distinct
      trends among genes.
AB  - The usage of alternative synonymous codons in the apicomplexan Cryptosporidium
      parvum has been investigated. A data set of 54 genes was analysed. Overall, A-
      and U-ending codons predominate, as expected in an A+T-rich genome. Two trends of
      codon usage variation among genes were identified using correspondence analysis.
      The primary trend is in the extent of usage of a subset of presumably
      translationally optimal codons, that are used at significantly higher frequencies
      in genes expected to be expressed at high levels. Fifteen of the 18 codons
      identified as optimal are more G+C-rich than the otherwise common codons, so that
      codon selection associated with translation opposes the general mutation bias.
      Among 40 genes with lower frequencies of these optimal codons, a secondary trend
      in G+C content was identified. In these genes, G+C content at synonymously
      variable third positions of codons is correlated with that in 5' and 3' flanking
      sequences, indicative of regional variation in G+C content, perhaps reflecting
      regional variation in mutational biases.

PMID- 11306120
TI  - Multiple origin of the dihomoxenous life cycle in sarcosporidia.
AB  - Although their ssrRNA gene sequences are closely related, the lizard
      sarcosporidia (Apicomplexa, Sarcocystidae) Sarcocystis lacertae and Sarcocystis
      gallotiae posses heteroxenous and dihomoxenous life cycles, respectively. When
      aligned with available sarcosporidian ssrRNA genes, both species constitute a
      monophyletic clade that is only distantly related with sarcosporidia that have a
      viperid snake as their definitive host (Sarcocystis sp., Sarcocystis atheridis).
      To test the phyletic status of the dihomoxenous life style, Sarcocystis
      rodentifelis and Sarcocystis muris, two dihomoxenous parasites of mammals were
      included into this study. All studied species group together with former
      Frenkelia spp., Sarcocystis neurona and related marsupial and bird sarcosporidia
      in a monophyletic clade. However, the available dataset supports independent
      appearance of the dihomoxenous life cycle at least twice during the evolution of
      the Sarcocystidae.

PMID- 11306121
TI  - Serological evidence for naturally occurring transmission of Neospora caninum
      among foxes (Vulpes vulpes).
AB  - The study describes the time course of the Neospora caninum-specific antibody
      response in experimentally infected foxes, in naturally N. caninum-seropositive
      vixens and their litters. An immunofluorescence test, a tachyzoite surface
      antigen based ELISA and an immunoblot assay were established for this purpose.
      The immunoblot patterns of naturally seropositive and experimentally infected
      foxes revealed a high degree of similarity and resembled those reported for other
      intermediate host species. Reactions against immunodominant antigens of Mr 56, 68
      and >94 kDa were observed which could be linked with a period of 14 days-2 months
      post experimental infection with tachyzoites. Cubs born by naturally seropositive
      vixens were found to be persistently or transiently seropositive, in the latter
      case, specific antibodies were detected only up to 44 days after birth. These
      antibodies may thus be of maternal origin. Differences between the immunoblot
      patterns of persistently positive cubs, those of their mothers and of transiently
      positive cubs, in particular the differential response to antigens of Mr 56 and
      68 kDa, prove that cubs with persistent antibodies had actively mounted an
      antibody response. This result provides the first evidence for the postnatal or
      vertical transmission of N. caninum among naturally seropositive foxes.

PMID- 11306122
TI  - Toxic marine microalgae.

PMID- 11306123
TI  - Purification and biochemical characterization of F II(a), a fibrinolytic enzyme
      from Agkistrodon acutus venom.
AB  - A fibrinolytic enzyme, F II(a), was isolated from Agkistrodon acutus venom by ion
      exchange chromatography and gel filtration. F II(a) consisted of a single
      polypeptide chain with a molecular weight of 26,000 and an isoelectric point of
      4.6. F II(a) was shown to solubilize fibrin and fibrinogen. F II(a) cleaved,
      primarily, the alpha chain of fibrinogen and fibrin followed by the beta chain,
      while the gamma chain was minimally affected. Thus, the enzyme was an alpha,beta
      fibrinogenase. The cleavage pattern of fibrinogen clearly varied from plasmin
      cleavage of the same molecule. In vivo, F II(a) had no influence on the rat's
      tissue-type plasminogen activator and plasminogen activator inhibitor-1
      activities in plasma. At the dosage of 5mg/kg, histological examination of heart,
      liver and lung tissue showed no hemorrhage. F II(a) is an enzyme that hydrolyzed
      fibrin directly without hemorrhagic activity.

PMID- 11306124
TI  - Systemic skeletal muscle necrosis induced by crotoxin.
AB  - Systemic skeletal muscle necrosis induced by crotoxin, the major component of the
      venom of Crotalus durissus terrificus, was investigated. Mice received an
      intramuscular injection of crotoxin (0.35mg/kg body weight) into the right
      tibialis anterior (TA) muscles, which were evaluated 3h, 24h and 3 days later.
      Control mice were injected with saline. Right and left TAs, gastrocnemius, soleus
      and right masseter and longissimus dorsi were removed and frozen. Histological
      sections were stained with Toluidine Blue or incubated for acidic phosphatase
      reaction. Three and 24h after the injection, signals of muscle fiber injury were
      found: (a) in the injected TA muscles; (b) in both right and contralateral soleus
      and red gastrocnemius; and (c) in the masseter muscles. Contralateral TA,
      longissimus dorsi and white gastrocnemius muscles were not injured. In
      conclusion, crotoxin induced a systemic and selective muscle injury in muscles or
      muscle regions composed by oxidative muscle fibers.

PMID- 11306125
TI  - Active-site mutagenesis of tetanus neurotoxin implicates TYR-375 and GLU-271 in
      metalloproteolytic activity.
AB  - Tetanus neurotoxin (TeNT) blocks neurotransmitter release by cleaving
      VAMP/synaptobrevin, a membrane associated protein involved in synaptic vesicle
      fusion. Such activity is exerted by the N-terminal 50kDa domain of TeNT which is
      a zinc-dependent endopeptidase (TeNT-L-chain). Based on the three-dimensional
      structure of botulinum neurotoxin serotype A (BoNT/A) and serotype B (BoNT/B),
      two proteins closely related to TeNT, and on X-ray scattering studies of TeNT, we
      have designed mutations at two active site residues to probe their involvement in
      activity. The active site of metalloproteases is composed of a primary sphere of
      residues co-ordinating the zinc atom, and a secondary sphere of residues that
      determines proteolytic specificity and activity. Glu-261 and Glu-267 directly co
      ordinates the zinc atom in BoNT/A and BoNT/B respectively and the corresponding
      residue of TeNT was replaced by Asp or by the non conservative residue Ala. Tyr
      365 is 4.3A away from zinc in BoNT/A, and the corresponding residue of TeNT was
      replaced by Phe or by Ala. The purified mutants had CD, fluorescence and UV
      spectra closely similar to those of the wild-type molecule. The proteolytic
      activity of TeNT-Asp-271 (E271D) is similar to that of the native molecule,
      whereas that of TeNT-Phe-375 (Y375F) is lower than the control. Interestingly,
      the two Ala mutants are completely devoid of enzymatic activity. These results
      demonstrate that both Glu-271 and Tyr-375 are essential for the proteolytic
      activity of TeNT.

PMID- 11306126
TI  - Secretory granule-cytoplasm relationships in serous glands of anurans:
      ultrastructural evidence and possible functional role.
AB  - A survey covering the serous (granular) cutaneous glands in several anuran
      families from the Old and New Worlds (Bombinatoridae, Discoglossidae, Ranidae,
      Hylidae, Pseudidae and Leptodactylidae) has revealed consistent patterns of
      complex interactions between the syncytial secretory unit and serous deposits
      (granules). These relationships involve outgrowths from the syncytial cytoplasm
      encircling the granules and complex invaginations of the perigranular compartment
      (halo) into the syncytium. The outgrowths are branched, cytoplasm processes
      resembling ramified microvilli, or can be larger, dome-like to cylindrical
      structures. Despite their different features and origins, all these structures
      are efficient devices for amplifying the cytoplasmic surfaces round the granules,
      so improving exchange between the secretory syncytium and serous product. These
      complex secretory granule-cytoplasm interactions affect the product released from
      the Golgi apparatus and are consistent with the hypothesis of prolonged serous
      maturation following the initial phase of biosynthesis. Post-Golgian maturation
      modifies the secretory material on a centripetal gradient, causing condensation
      and, possibly, the transfer of component molecules from and/or to the cytoplasm.

PMID- 11306127
TI  - Pharmacological modulation of hyperalgesia induced by Bothrops asper (terciopelo)
      snake venom.
AB  - The ability of Bothrops asper snake venom to cause hyperalgesia was investigated
      in rats, using the paw pressure test. Intraplantar injection of the venom (5-15
      microg/paw) caused a dose and time-related hyperalgesia, which peaked 2h after
      venom injection. Bothrops asper venom-induced hyperalgesia was blocked by the
      bradykinin B(2) receptor antagonist HOE 140 and attenuated by dexamethasone, an
      inhibitor of phospholipase A(2). Inhibition of the lipoxygenase pathway by NDGA
      abrogated the algogenic phenomenon. The hyperalgesic response was not modified by
      pretreatment with indomethacin, an inhibitor of the cyclo-oxygenase pathway, by
      meloxicam, an inhibitor of the type 2 cyclo-oxygenase pathway, by the PAF
      receptor antagonist BN52021 or by anti-TNF-alpha or anti-interleukin 1
      antibodies. Intraplantar injection of the venom also caused an oedematogenic
      response which was not modified by any of these pharmacological treatments. These
      results suggest that hyperalgesia induced by Bothrops asper venom is, at least
      partially, mediated by bradykinin, phospholipase A(2) activity and leukotrienes.
      Distinct mechanisms are involved in the development of hyperalgesia and oedema
      induced by the venom.

PMID- 11306128
TI  - Different methods for toxin analysis in the cyanobacterium Nodularia spumigena
      (Cyanophyceae).
AB  - The brackish water cyanobacterium Nodularia spumigena produce the hepatotoxic
      cyclic pentapeptide nodularin. Intoxications for both human as well as animal may
      arise when water reservoirs are contaminated with potentially toxic Nodularia
      species. Here, results of three independent methods for the determination of
      nodularin in different strains of N. spumigena are presented. The results
      obtained with a protein phosphatase assay and a HPLC/UV/MS method are compared
      with the results obtained with a bioluminescence assay, which is successfully
      introduced here for nodularin determination. Statistical evaluation of the three
      applied methods revealed a good comparability towards the detected toxin content.
      The methods were evaluated taking into consideration the parameters: handling,
      efficiency, sensitivity and selectivity. The detection limit in the protein
      phosphatase assay is highest (0.05ng nodularin) and lowest (250ng nodularin) in
      the bioluminescence assay- it was determined with 5ng (MS) and 25ng (UV) for the
      HPLC/UV/MS methods. The different selectivities and sensitivities are critically
      discussed and an analytical pathway for the determination of the biotoxin
      nodularin from Nodularia samples is proposed.

PMID- 11306129
TI  - Cloning and characterization of cDNA sequences encoding two novel alpha-like
      toxin precursors from the Chinese scorpion Buthus martensii Karsch.
AB  - According to a relative conserved fragment of alpha-scorpion toxins, a degenerate
      primer was designed and synthesized. Two full-length cDNAs encoding the
      precursors of two novel putative alpha-like-toxins were then amplified from the
      total cDNAs of venomous glands of the Chinese scorpion Buthusmartensi Karsch
      using 3' and 5' RACE (rapid amplification of cDNA ends). The precursors were both
      composed of 85 amino acid residues, including a putative signal peptide of 19
      residues and a mature toxin of 66 residues, respectively. The predicted amino
      acid sequences of these two toxins show a homology of 82% with each other, and of
      55-70% with other BmK-originated alpha-like-toxins. Interestingly, it is rarely
      seen in other alpha or alpha-like-toxins that: (1) Met residue but not a basic
      amino acid residue (Arg or Lys) is located on position 58 for BmKalpha2; (2) both
      toxins are ended with double Gly in the C-terminus.

PMID- 11306130
TI  - Morphological and toxicological variability of Prorocentrum lima clones isolated
      from four locations in the south-west Indian Ocean.
AB  - Eight clones of the toxic dinoflagellate Prorocentrum lima (Ehrenberg) Dodge from
      four sites (two clones per site) on the coral reef of La Reunion, Mayotte,
      Europa, and Mauritius Islands in the SW Indian Ocean were isolated and cultivated
      under the same conditions. Morphological features of each clone, including cell
      size and valve and marginal pore numbers, were examined by scanning electron
      microscopy. The toxic potential of each clone was determined by protein
      phosphatase type 2A (PP2A) inhibition test and fibroblast cell line FR3T3
      bioassay. Scanning electron microscopy showed that variation in morphological
      features of clones within and between sites was minimal and not significant.
      However, equivalent okadaic acid content, determined by PP2A assay, was different
      within and between clones isolated from the four islands. Cytotoxicity bioassay
      with the FR3T3 cell line confirmed the variation on global toxic potential within
      and between the eight P. lima clones. This test also suggested the presence of
      other toxic compounds without PP2A inhibiting activity in crude extracts of some
      clones.

PMID- 11306131
TI  - Purification and characterization of jerdofibrase, a serine protease from the
      venom of Trimeresurus jerdonii snake.
AB  - A fibrin(ogen)olytic serine protease from Trimeresurus jerdonii venom was
      identified and purified to SDS-polyacrylamide gel electrophoresis homogeneity. It
      is a single chain polypeptide with a molecular weight of 32kDa under reduced
      condition and 28kDa under non-reduced condition, respectively. The venom protease
      catalysed the hydrolysis of some chromogenic substrates such as S2238, S2160,
      S2302 and S2251. It degraded Bbeta-chain of human fibrinogen preferentially. Also
      the enzyme degraded fibrin directly. Its enzymatic activity was completely
      inhibited by phenylmethylsulfonyl fluoride (PMSF), but not affected by EDTA. That
      suggested it was a serine protease. N-terminal sequence of the purified component
      showed high homology with other snake venom serine proteases.

PMID- 11306132
TI  - Expression and processing of recombinant sarafotoxins precursor in Pichia
      pastoris.
AB  - Sarafotoxins are peptides isolated from the Atractaspis snake venom, with strong
      constrictor effect on cardiac and smooth muscle. They are structurally and
      functionally related to endothelins. The sarafotoxins precursor cDNA predicts an
      unusual structure 'rosary-type', with 12 successive similar stretches of
      sarafotoxin (SRTX) and spacer. In the present work, the recombinant precursor of
      SRTXs was sub-cloned and expressed in the yeast Pichia pastoris, and secreted to
      the culture medium. Characterization by SDS-PAGE, immunoblot, mass spectrometry
      and biological activity, suggests that intact precursor was expressed but
      processing into mature toxins also occurred. Furthermore, our results indicate
      that the correct proportion of sarafotoxin types as contained in the precursor,
      is obtained in the yeast culture medium. Contractile effects of the expressed
      toxins, on rat and Bothrops jararaca isolated aorta, were equivalent to 5x10(
      10)M and 5x10(-11)M of sarafotoxin b, respectively. The enzymes responsible for
      the complete maturation of sarafotoxins precursor are still unknown. Our results
      strongly suggest that the yeast Pichia pastoris is able to perform such a
      maturation process. Thus, the yeast Pichia pastoris may offer an alternative to
      snake venom gland to tentatively identify the molecular process responsible for
      SRTXs release.

PMID- 11306133
TI  - First report of the cyanobacterial toxin cylindrospermopsin in New Zealand.
AB  - Cylindrospermopsin, a hepatotoxin produced by cyanobacteria, has been
      unambiguously detected in cyanobacteria collected from a recreational lake in the
      Wellington region of New Zealand. To our knowledge this is the first report of
      cylindrospermopsin in New Zealand. Cylindrospermopsin and several microcystins
      were identified by reversed phase high-performance liquid chromatography-mass
      spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS) using an atmospheric
      pressure ionization source and an ionspray interface. The presence of
      cylindrospermopsin in New Zealand highlights the risk of direct cyanobacterial
      toxin exposure in recreational waters.

PMID- 11306134
TI  - UT841 purified from sea urchin (Toxopneustes pileolus) venom inhibits time
      dependent (45)Ca(2+) uptake in crude synaptosome fraction from chick brain.
AB  - To clarify the mechanism by which the toxic abstract from Toxopneustes pileolus
      inhibits time-dependent (Time-dep.) Ca(2+) uptake in crude synaptosome fraction,
      the effective component from pedicellarial venom of the sea urchin was purified.
      The crude extracts were purified by a series of steps including ion exchange
      (DEAE-sephadex-A25 gel), gel filtration (with Superdex-2000 and Superdex-peptide
      columns) and reversed-phase chromatography (Sephasil-C18 column). The effective
      component that inhibited Time-dep. 45Ca(2+) uptake was purified and named UT841.
      Its IC(50) was determined to be lower than 35ng/ml. UT841 is an acidic protein
      with an apparent molecular weight of about 18,000. The N-terminal sequence (40
      amino acids) was almost identical to that of Contractin A (a protein purified
      from the same kind of venom which induces smooth muscle contraction). Even though
      it is unclear whether or not UT841 is Contractin A, Ca(2+) mobilization in nerve
      cells was shown to be influenced by UT841. This investigation also revealed that
      a donor of nitric oxide, arachidonic acid and an inhibitor of phospholipase C
      selectively inhibit Time-dep. (45)Ca(2+) uptake. These results suggest that UT841
      purified from sea urchin venom may affect Time-dep. (45)Ca(2+) uptake through the
      metabolism of some lipids and nitric oxide.

PMID- 11306135
TI  - Cardiovascular effects of lepadiformine, an alkaloid isolated from the ascidians
      Clavelina lepadiformis (Muller) and C. moluccensis (Sluiter).
AB  - The effects of lepadiformine, a natural marine alkaloid isolated from the
      ascidians Clavelina lepadiformis (Muller) and C. moluccensis (Sluiter), were
      studied in vivo by arterial blood pressure (aBP) recordings and
      electrocardiograms (ECG) in anaesthetised rats and in situ by peripheral vascular
      pressure recordings on perfused rabbit ear. Transmembrane resting (RP) and action
      (AP) potentials were also recorded by intracellular microelectrodes on
      electrically stimulated left ventricular papillary muscle and spontaneously
      beating atrium isolated from rat and frog hearts, respectively. Intravenous
      injection of lepadiformine (6mg/kg) produced marked bradycardia and a lengthening
      of ECG intervals as well as a transient decrease of aBP, which rapidly returned
      to normal. The decrease of aBP may have been related to a vasoconstrictor effect
      observed in the perfused ear experiment. Lepadiformine did not alter RP, but
      significantly lengthened the repolarising phase of AP in rat papillary muscle and
      frog atrium. Lepadiformine also mimicked the effect of Ba(2+) (0.2mM) on the rat
      AP repolarising phase. Moreover, the lengthening of the AP in frog atrium induced
      by lepadiformine still developed after the delayed outward K(+) current (I(K))
      was blocked by tetraethylammonium (10mM). These observations suggest that
      lepadiformine-induced lengthening of AP duration was not due to a decrease of
      I(K), but may reasonably be attributed to a reduction of the inward rectifying
      K(+) current (I(K1)). This blockade of I(K1) could account for the cardiovascular
      effects of lepadiformine in vivo and in vitro and suggests that lepadiformine has
      antiarrhythmic properties.

PMID- 11306136
TI  - Inhibition of egg hatching success and larvae survival of the scallop, Chlamys
      farreri, associated with exposure to cells and cell fragments of the
      dinoflagellate Alexandrium tamarense.
AB  - We report an apparently novel toxic effect of the dinoflagellate Alexandrium
      tamarense, manifested by inhibition of the egg hatching success of the scallop,
      Chlamys farreri. The hatching rate of C. farreri approached only 30% of controls
      when its fertilised eggs were exposed for 36h to A. tamarense cells or cellular
      fragments at a concentration of 100 cells/ml, and the hatching rate was just 5%
      after exposure to A. tamarense of 500 cells/ml. Similar exposures of the
      fertilised scallop eggs to two other algal species, the diatom Phaeodactylum
      tricornutum and the raphidophyte Heterosigma carterae, resulted in no such
      toxicity or inhibitory effects. Likewise, exposure of eggs to standard STX toxin,
      as well as to A. tamarense cell contents (supernant of re-suspended algal cells
      following ultrasonication and centrifugation), did not elicit this inhibitory
      response. However, exposure of the scallop eggs to cell cultures, intact algal
      cells, or cell fragments of A. tamarense produced marked toxicity. The alga also
      influenced larvae at early D-shape stage of scallop. The survival rates began to
      decrease significantly after exposed for 6 days at concentration of 3000 cells/ml
      and above; no larvae could survive after 14-day exposure to A. tamarense at
      10,000 cells/ml or 20-day at 5000 cells/ml. The results indicated the production
      of novel substances from A. tamarense which can cause adverse effects on egg
      hatching and survival of the scallop larvae. The experiment also found that the
      developmental stages before blastula was the developmental period most sensitive
      to the A. tamarense toxin(s) and the alga at early exponential stage had the
      strongest effect on egg hatching comparing with other growth phases. The adverse
      effect of A. tamarense on early development of scallops may cause decline of
      shellfish population and may have further impact on marine ecosystem.

PMID- 11306137
TI  - Domoic acid accumulation in French shellfish in relation to toxic species of
      Pseudo-nitzschia multiseries and P. pseudodelicatissima.
AB  - Within the French phytoplankton monitoring network (REPHY), domoic acid (DA), the
      toxin responsible for amnesic shellfish poisoning, was first detected in samples
      collected in 1998. Toxin analysis by the official method [liquid chromatography
      with diode array detection (LC/DAD)] was performed when Pseudo-nitzschia cell
      concentration was greater than 1.0 x 10(5) cells/l. LC/DAD results obtained in
      1999 and 2000 showed increased DA accumulation in bivalves sampled at different
      sites along French coasts. The toxin maximum in 1999 was 3.2 microg DA/g of whole
      tissue, whereas the levels in 2000 (53 microg) were above the sanitary threshold
      (20 microg DA/g tissue). Phytoplankton samples collected during blooms were
      observed by both light and scanning electron microscopy (SEM). Identification of
      phytoplankton species by SEM analyses confirmed the presence of two known DA
      producing species, P. pseudodelicatissima and P. multiseries. LC/DAD results for
      a mass culture of P. multiseries indicated that this species was involved in DA
      accumulation in French shellfish.

PMID- 11306138
TI  - Primary structure of two cytolysin isoforms from Stichodactyla helianthus
      differing in their hemolytic activity.
AB  - Sticholysin I (St-I) and sticholysin II (St-II) are cytolysins purified from the
      sea anemone Stichodactyla helianthus with a high degree of sequence identity
      (93%) but clearly differenced in their hemolytic activity. In order to go further
      into the structural determinants for the different behavior of St-I and St-II, we
      report here the complete amino acid sequences and the consensus secondary
      structure prediction of both proteins. The complete determination of St-II
      primary structure confirms the partial revision of cytolysin III amino acid
      sequence. All nonconservative changes between St-I and St-II are located at the N
      terminal. According to our prediction these changes could be located at the same
      face of an alpha-helix during pore formation events and could account for the
      observed differences in hemolytic activity between St-I and St-II.

PMID- 11306139
TI  - Isolation and sequence determination of peptides in the venom of the spider wasp
      (Cyphononyx dorsalis) guided by matrix-assisted laser desorption/ionization time
      of flight (MALDI-TOF) mass spectrometry.
AB  - Micro-scale (sub-pmol) isolation and sequence determination of three peptides
      from the venom of the solitary spider wasp Cyphononyx dorsalis is described. We
      isolated two novel peptides Cd-125 and Cd-146 and a known peptide Thr(6)
      bradykinin from only two venom sacs of solitary spider wasp Cyphononyx dorsalis
      without bioassay-guided fractionation, but instead guided by MALDI-TOF MS. The
      MALDI-TOF MS analysis of each fraction showed the purity and molecular weight of
      the components, which led to the isolation of the peptides virtually without loss
      of sample amount. The sequences of the novel peptides Cd-125 (Asp-Thr-Ala-Arg-Leu
      Lys-Trp-His) and Cd-146 (Ser-Glu-Thr-Gly-Asn-Thr-Val-Thr-Val-Lys-Gly-Phe-Ser-Pro
      Leu-Arg) were determined by Edman degradation together with mass spectrometry,
      and finally corroborated by solid-phase synthesis. The known peptide Thr(6)
      bradykinin (Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg) was identified by comparison
      with the synthetic authentic specimen. This is the first example for any kinins
      to be found in Pompilidae wasp venoms. The procedure reported here can be
      applicable to studies on many other components of solitary wasp venoms with
      limited sample availability.

PMID- 11306140
TI  - The levels of tetrodotoxin and its analogue 6-epitetrodotoxin in the red-spotted
      newt, Notophthalmus viridescens.
AB  - Tetrodotoxin (TTX) and its analogue 6-epiTTX were detected in 11-12 specimens of
      the red-spotted newt, Notophthalmus viridescens, by a post-column fluorescent
      HPLC system and by LC/MS in selected ion monitoring mode. TTX levels varied
      considerably among individuals from low (less than 0.15 microg TTX/g newt) to
      high concentrations (23.5 microg TTX/g newt), while 6-epiTTX was found to be a
      minor constituent in all specimens.

PMID- 11306141
TI  - Facilitation of functional compartmentalization of bone marrow cells in leukemic
      mice by biological response modifiers: an immunotherapeutic approach.
AB  - Biological Response Modifiers (BRMs) including interleukin-2 (IL-2), interferon
      gamma (IFN-gamma) and sheep erythrocytes (SRBC) protected N,N'-ethylnitrosourea
      (ENU) induced leukaemic mice. Two cell types from the bone marrow were isolated
      in density specific gradient representing two distinct compartments, the low
      density cells being more CD34 positive than the high density group.
      Investigations with the functional efficacy of such compartments revealed
      significant improvement of cytotoxic efficacy and phagocytic burst at the high
      density compartment (HDC) level. The high density compartment was found to be
      more responsive towards the BRMs compared to the cells of the low density
      compartment (LDC). It was suggested that use of BRMs in vivo can stimulate a
      potent functional progenitor compartmentalization in normal as well as leukaemic
      mice. These observations are expected to help a logistic approach towards
      combined BRM therapy at the clinical level.

PMID- 11306142
TI  - Dexamethasone inhibits the antigen presentation of dendritic cells in MHC class
      II pathway.
AB  - Glucocorticoids (GC) are physiological inhibitors of inflammatory responses and
      are widely used as anti-inflammatory and immunosuppressive agents in treatment of
      many autoimmune and allergic diseases. In the present study, we demonstrated that
      one of the mechanisms by which GC can suppress the immune responses is to inhibit
      the differentiation and antigen presentation of dendritic cells (DC). DC were
      differentiated from murine bone marrow hematopoietic progenitor cells by culture
      with GM-CSF and IL-4 with or without dexamethasone (Dex). Our data showed that
      Dex, in a dose dependent manner, down-regulated surface expression of CD86, CD40,
      CD54 and MHC class II molecules by DC, but the expression of MHC class I, CD80,
      CD95 and CD95L were not affected. In addition, Dex-treated DC showed an impaired
      function to activate alloreactive T cells and to secrete IL-Ibeta and IL-12p70.
      Moreover, Dex inhibited DC to present antigen by MHC class II pathway. However,
      the endocytotic activity of DC was not affected. The inhibitory effect of Dex on
      the expression of costimulatory molecules and the antigen-presenting capacity of
      DC could be blocked by the addition of RU486, a potent steroid hormone
      antagonist, suggesting the requirement of binding to cytosolic receptors in the
      above-described action of Dex. Since DC have the unique property to present
      antigen to responding naive T cells and are required in the induction of a
      primary response, the functional suppression of DC by Dex may be one of the
      mechanisms by which GC regulate immune responses in vivo.

PMID- 11306143
TI  - Catalytic heterogeneity of polyclonal DNA-hydrolyzing antibodies from the sera of
      patients with multiple sclerosis.
AB  - Various catalytic antibodies or abzymes have been detected recently in the sera
      of patients with several autoimmune pathologies, where their presence is most
      probably associated with autoimmunization. Recently we have shown that DNase
      activity is associated with IgGs from the sera of patients with multiple
      sclerosis (MS) but not with those from the sera of normal humans. Here we present
      evidence showing that MS IgG, its F(ab) fragments, and separated L-chains
      catalyze DNA hydrolysis. The properties of the DNase activity of these polyclonal
      IgGs distinguish them from other known human DNases. In addition, their specific
      activities with different oligonucleotide substrates and the range of optimal
      pHs, apparent K(M) values and substrate specificities varied widely for different
      patients. The findings speak in favor of the generation by the immune systems of
      individual patients of a variety of polyclonal catalytic IgG pools, from
      relatively small to extremely large ones.

PMID- 11306144
TI  - Survivin expression correlates with apoptosis resistance after lymphocyte
      activation and is found preferentially in memory T cells.
AB  - The prevention of apoptosis may be critical for immunological function. Survivin
      is a recently cloned member of the inhibitor of apoptosis protein family. We
      analyzed survivin expression before and after lymphocyte activation in isolated
      cell populations. Prior to activation, survivin was undetectable. After
      activation with IL-2 and OKT-3, CD3(+) cells expressed survivin. Next, we
      correlated survivin expression with Fas, FasL and the amount of apoptosis over
      time in culture. After activation, survivin was readily detected by day 2 and
      decreased thereafter. Prior to activation (day 0), Fas was present on 60% of the
      cells and on 100% by days 2-6. Peak FasL mRNA expression was at day 2. During
      peak survivin expression (days 2-4) the apoptotic fraction was low, but when
      survivin expression decreased the apoptotic fraction increased rapidly. Finally,
      we found that CD45RO(+) memory T cells showed a higher expression of survivin
      than did CD45RA(+) naive T cells after activation. These results suggest that
      survivin may contribute to T-cell survival early in T-cell responses as well as
      in memory immune responses.

PMID- 11306145
TI  - Inhibition of effects of endogenously synthesized histamine disturbs in vitro
      human dendritic cell differentiation.
AB  - Histamine, a principal mediator in various physiological and pathological cell
      functions is synthesized from L-histidine exclusively by histidine decarboxylase,
      an enzyme, which is expressed in many tissues of mammalian organism. Histamine
      plays a role in various cellular functions, including cell differentiation. The
      aim of this study was to determine the presence and to characterize the role of
      the endogenously produced histamine during in vitro dendritic cell (DC)
      differentiation induced by interleukin-4 (IL-4) and granulocyte-monocyte colony
      stimulating factor (GM-CSF). The changes in intracellular histamine content,
      biosynthesis and gene expression of histidine decarboxylase were investigated
      during this process. One also studied how histamine receptor antagonists and a
      histamine synthesis blocker influence the expression of differentiation antigens
      on the DC during in vitro maturation. During in vitro differentiation parallel
      culture incubations were performed by adding H1 receptor antagonist triprolidine,
      H2 receptor antagonist tiotidine, the tamoxifene derivate DPPE which blocks the
      intracellular binding of histamine, and an irreversible blocker of histidine
      decarboxylase, alpha-fluoromethyl histamine (alpha-FMH). The results show
      simultaneous increase in both histidine decarboxylase level and histamine content
      during differentiation of elutriated monocytes toward DC. Both blockade of de
      novo histamine production (by alpha-FMH) and inhibition of histamine binding (by
      H1 and H2 receptor antagonists, triprolidine and tiotidine, respectively)
      markedly decreased CD40 expression and that of CD45 from the 3rd day of
      treatment. DPPE by disturbing intracellular interaction of histamine with
      cytochrome P-450 moieties was able to decrease the expression of CD45, CD86, HLA
      DR, CD33, CD40 and CD11c. Based on the data it is suggested that endogenous
      histamine is actively synthesized during cytokine-induced in vitro DC
      differentiation. The functional relevance and autocrine and paracrine action of
      endogenously produced histamine is supported by the data showing that inhibition
      of histamine synthesis by HDC, blocking of histamine binding by both
      'extracellular' histamine receptors (by specific antagonists, triprolidine and
      tiotidine) and 'intracellular' antagonists (DPPE) disturb the differentiation of
      DC. This conclusion is supported by the fact, that by the inhibition of histamine
      acting in an autocrine/paracrine way, the expression pattern of differentiation
      markers on DC is markedly changed.

PMID- 11306146
TI  - Differential clonal expansion of CD4 and CD8 T cells in response to 4-1BB
      ligation: contribution of 4-1BB during inflammatory responses.
AB  - Cell surface proteins of the tumor necrosis factor (TNF) family of receptors have
      been intimately involved in inducing T cell death. A feature of these family
      members that is less well studied is their ability to rescue T cells from
      apoptosis. One such member is 4-1BB; an activation induced surface receptor on
      CD4 and CD8 T cells. This study demonstrates that the costimulatory effects of 4
      1BB, which was found to enhance clonal expansion, required cross-linking of the
      receptor. The survival of the activated CD8 T cells following expansion was not
      associated with an increase in Bcl-2 expression. Provided that 4-1BB signaling
      was present, the amplification of activated CD8 T cell growth in vivo was
      independent of CD28 ligation. In vivo clonal expansion of activated CD4 T cells,
      however, was not as responsive to 4-1BB cross-linking. Moreover, 4-1BB-induced
      expansion was comparable to that mediated by LPS which can incite multiple
      costimulatory signals. Furthermore, LPS-mediated growth and survival of
      superantigen (SAg) stimulated T cells appeared to be partially dependent on
      interactions between 4-1BB and 4-1BB ligand (4-1BBL).

PMID- 11306147
TI  - CCR1-specific non-peptide antagonist: efficacy in a rabbit allograft rejection
      model.
AB  - The classic signs of acute cellular rejection during organ transplantation
      include the infiltration of mononuclear cells into the interstitium. This
      recruitment of leukocytes into the transplanted tissue is promoted by chemokines
      like RANTES. Since RANTES is a potent agonist for the CC chemokine receptor CCR1,
      we examined whether the CCR1 antagonist BX 471 was efficacious in a rabbit kidney
      transplant rejection model. BX 471 was able to compete with high affinity with
      the CCR1 ligands MIP-1alpha and RANTES for binding to HEK 293 cells expressing
      rabbit CCR1. BX 471 was a competitive antagonist of rabbit CCR1 in Ca(2+) flux
      studies. Two separate studies in which animals were subcutaneously implanted with
      slow release pellets of BX 471 demonstrated that animals implanted with BX 471
      had increased survival compared with untreated controls or animals implanted with
      placebo. The mean survival time for the placebo group was 12.33+/-1.7 days. The
      animals in the BX 471 treated group had mean survival times of 16.9+/-2.1 and
      16.0+/-1.7 days, respectively, for the two studies. Analysis of the combined data
      by Student t-test gave a P value of 0.03 that is significant at the 0.05 level.
      In addition, there was a marked reduction in the urea and creatinine levels in
      the BX 471 treated animals compared with the control and placebo groups in both
      studies. Finally, pathologic analysis of the kidneys in the rabbit renal
      transplantation model from animals in the different groups showed that BX 471 was
      similar to cyclosporin in its ability to prevent extensive infarction of
      transplanted kidneys. Based on the data from these studies, BX 471 shows clear
      efficacy at the single dose tested compared with animals treated with placebo.

PMID- 11306148
TI  - Calculating confidence intervals for the number needed to treat.
AB  - The number needed to treat (NNT) has gained much attention in the past years as a
      useful way of reporting the results of randomized controlled trials with a binary
      outcome. Defined as the reciprocal of the absolute risk reduction (ARR), NNT is
      the estimated average number of patients needed to be treated to prevent an
      adverse outcome in one additional patient. As with other estimated effect
      measures, it is important to document the uncertainty of the estimation by means
      of an appropriate confidence interval. Confidence intervals for NNT can be
      obtained by inverting and exchanging the confidence limits for the ARR provided
      that the NNT scale ranging from 1 through infinity to -1 is taken into account.
      Unfortunately, the only method used in practice to calculate confidence intervals
      for ARR seems to be the simple Wald method, which yields too short confidence
      intervals in many cases. In this paper it is shown that the application of the
      Wilson score method improves the calculation and presentation of confidence
      intervals for the number needed to treat. Control Clin Trials 2001;22:102-110

PMID- 11306149
TI  - A self-designing rule for clinical trials with arbitrary response variables.
AB  - For testing both one-sided and two-sided hypotheses concerning several treatment
      arms in group sequentially performed clinical trials with arbitrary outcome
      variables, a general method is considered that allows one to completely self
      design a study. All information available prior to a stage is used for estimating
      the sample size and the weight for the next step. In "using up" the variance, the
      test statistic is built in a bounded finite but random number of stages to test
      just once the rejection of the null hypothesis. Control Clin Trials 2001;22:111
      116

PMID- 11306150
TI  - A three-outcome design for phase II clinical trials.
AB  - The goal of a phase II trial is to make a preliminary determination regarding the
      activity and tolerability of a new treatment and thus to determine whether the
      treatment warrants further study in the phase III setting. Phase II clinical
      trials are typically designed in the hypothesis testing framework with two
      possible outcomes, either reject the null hypothesis H(0) or reject the
      alternative hypothesis H(a), based on the observed activity level. However, in
      cases where the observed activity is "borderline," the decision regarding the
      future of the agent is not as clear as the prespecified hypothesis test would
      indicate. In this paper we propose an alternative design that allows for three
      outcomes: reject H(0), reject H(a), or reject neither. We describe the
      theoretical properties of this design and illustrate it with several examples. We
      focus on the clinical implications of the three-outcome design. Control Clin
      Trials 2001;22:117-125

PMID- 11306151
TI  - Isotonic designs for phase I trials.
AB  - The purpose of a phase I trial in cancer is to determine the level (dose) of the
      treatment under study that has an acceptable level of adverse effects. Although
      substantial progress has recently been made in this area using parametric
      approaches, the method that is widely used is based on treating small cohorts of
      patients at escalating doses until the frequency of toxicities seen at a dose
      exceeds a predefined tolerable toxicity rate. This method is popular because of
      its simplicity and freedom from parametric assumptions. In this paper, we
      consider cases in which it is undesirable to assume a parametric dose-toxicity
      relationship. We propose a simple model-free approach by modifying the method
      that is in common use. The approach assumes toxicity is nondecreasing with dose
      and fits an isotonic regression to accumulated data. At any point in a trial, the
      dose given is that with estimated toxicity deemed closest to the maximum
      tolerable toxicity. Simulations indicate that this approach performs
      substantially better than the commonly used method and it compares favorably with
      other phase I designs. Control Clin Trials 2001;22:126-138

PMID- 11306152
TI  - Who's on first? what's on second?

PMID- 11306153
TI  - ACTG (AIDS Clinical Trials Group) 384: a strategy trial comparing consecutive
      treatments for HIV-1.
AB  - ACTG (AIDS Clinical Trials Group) 384 is designed to evaluate different
      strategies for antiretroviral treatment in HIV-1-infected individuals with no
      previous exposure to antiretroviral treatment. The study is a randomized,
      partially double-blinded, controlled trial with 980 subjects at 81 centers in the
      United States and Italy. The study has a factorial design that addresses the
      following scientific questions: (1) Does the best initial choice of therapy
      include both a protease inhibitor (PI) and non-nucleoside reverse transcriptase
      inhibitor (NNRTI) in a four-drug combination with nucleoside analogue (NRTI)
      drugs, or should these agents be used sequentially in three-drug combinations?;
      (2) Which sequence is best in a three-drug regimen-PI followed by NNRTI or NNRTI
      followed by PI ?; (3) Which is the best sequence of dual NRTI combinations
      zidovudine plus lamivudine followed by didanosine plus stavudine, or the
      converse? Subjects in the three-drug combination arms are offered a salvage
      regimen after failure of their second regimen; subjects in the four-drug
      combination arm are offered a salvage regimen after failure of their first
      regimen. The primary endpoint of the study is the time until salvage; secondary
      endpoints include time to virological failure and time to toxicity-related
      discontinuation of therapy. A Division of AIDS Data and Safety Monitoring Board
      will review the trial for safety and efficacy. Control Clin Trials 2001;22:142
      159

PMID- 11306154
TI  - An open-label randomized trial to evaluate different therapeutic strategies of
      combination therapy in HIV-1 infection: design, rationale, and methods of the
      initio trial.
AB  - This article discusses the design of an ongoing open-label, randomized trial
      comparing three strategies of initial and subsequent HIV therapy in terms of long
      term immunological and virological effect. The three treatment arms are (1)
      didanosine (ddI) plus stavudine (d4T) plus efavirenz (EFV) followed by zidovudine
      (ZDV) plus lamivudine (3TC) plus abacavir (ABC) plus nelfinavir (NFV); (2) ddI
      plus d4T plus NFV followed by ZDV plus 3TC plus ABC plus EFV; (3) ddI plus d4T
      plus EFV plus NFV followed by ZDV plus 3TC plus ABC plus saquinavir plus
      ritonavir. The primary objective is to determine whether it is best to start with
      a protease inhibitor (PI)-containing regimen, a non-nucleoside analogue reverse
      transcriptase inhibitor (NNRTI)-containing regimen, or with a regimen containing
      both a PI and an NNRTI. The aim is to recruit over 1000 patients followed for at
      least 3 years. The entry criteria are broad with no restriction on stage of
      disease, CD4 count, or HIV viral load. The criteria for therapeutic failure
      determining change of treatment are not defined and are left to the clinicians,
      but randomization is stratified by country and by the current criteria used for
      changing treatment. We describe the rationale behind various aspects of the
      design and discuss the complexities involved in undertaking such a large trial in
      HIV-infected patients from 180 clinical sites in 17 countries. Control Clin
      Trials 2001;22:160-175

PMID- 11306155
TI  - The rationale and design of the CPCRA (Terry Beirn Community Programs for
      Clinical Research on AIDS) 058 FIRST (Flexible Initial Retrovirus Suppressive
      Therapies) trial.
AB  - The CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 058
      FIRST (Flexible Initial Retrovirus Suppressive Therapies) trial is a large, long
      term, randomized, prospective comparison of three different antiretroviral
      strategies in highly active antiretroviral therapy-naive, HIV-1-infected persons.
      The trial was designed as a flexible framework upon which other studies could be
      added to answer more limited, but still important, questions. This article
      presents the study design, discusses the challenges we have faced in implementing
      the trial, and describes our preliminary experiences. Control Clin Trials
      2001;22:176-190

PMID- 11306156
TI  - Challenges with studies investigating longevity of dental restorations--a
      critique of a systematic review.
AB  - OBJECTIVES: A systematic review is a method of evaluating the published and
      unpublished literature relating to a specific area or topic. The objectives of
      this paper are to identify and discuss problems encountered in synthesising the
      available literature; and to make recommendations for the future conduct and
      reporting of clinical trials that aim to determine the longevity of dental
      restorations. DATA SOURCES: Studies were identified by a wide search of published
      and unpublished material in any language using a large number of general and
      specialist data bases, hand searching of key dental journals and searching of
      abstracts from conference proceedings. STUDY SELECTION: Pre-defined inclusion
      criteria based on objective outcome measures of restoration longevity and study
      designs were applied to determine study selection. CONCLUSIONS: A review of the
      longevity of dental restorations completed recently encountered substantial
      problems in designing an appropriate protocol to address this issue. The review
      found that many of the factors reported previously as affecting restoration
      longevity could not be confirmed using the agreed systematic review protocol that
      incorporated an objective study design. Further, the multiplicity of study
      designs, and reporting methods found in the literature made meta-analyses
      impossible. A proforma is proposed in order to aid the design of future research
      into the longevity of restorations.

PMID- 11306157
TI  - Influence of Carisolv for resin adhesion to sound human primary dentin and young
      permanent dentin.
AB  - OBJECTIVE: This study evaluated the influence of Carisolv (Medi Team) for resin
      adhesion to sound human primary and young permanent dentin. METHOD: The buccal
      surfaces of 64 primary molars and 74 premolars were used. Two adhesive systems
      and resin composites were used; SD: Super-Bond D Liner DUAL (Sun Medical) and
      Clearfil Photo Anterior(Kuraray), and FB: Imperva Fluorobond and Lite-Fil IIA
      (Shofu). Ten groups were prepared. Groups 1-5 were primary dentin and Groups 6-10
      were permanent dentin. Groups 1 and 6: Carisolv applied and agitated for 3min, SD
      was used. Groups 2 and 7: etched with 10-3 solution (Sun Medical) for 10s, SD was
      used. Groups 3 and 8: treated with Carisolv and then etched, SD was used. Groups
      4 and 9: treated with Carisolv, FB was used. Groups 5 and 10: FB was used. The
      microstructural effects of Carisolv, 10-3 solution and Carisolv plus 10-3
      solution applied to dentin were evaluated by SEM. In addition, the microstructure
      of the resin-dentin interfaces of each group were studied using SEM. Shear bond
      strengths (SBS) were tested, and the failed surfaces were observed using SEM.
      Data was statistically analyzed using ANOVA with subsequent application of post
      hoc Duncan's new multiple range test at p<0.05. RESULTS: The effect of Carisolv
      on primary dentin was stronger than that to permanent dentin. The mean SBS
      (unit:MPa) of Groups 1-10 were: 5.6, 15.8, 7.6, 17.5, 13.5, 8.1, 16.2, 18.2, 31.4
      and 15.5. The SBS of Group 9 (Carisolv treated permanent dentin) was
      significantly higher than those of other groups. There was no significant
      difference of SBS among Groups 2, 4, 5, 7, 8 and 10, Groups 3, 5 and 6, and
      Groups 1, 3 and 6. SIGNIFICANCE: Carisolv treatment before etching significantly
      decreased the SBS to primary dentin in SD groups, but significantly increased the
      SBS to permanent dentin in FB groups.

PMID- 11306158
TI  - Factors affecting patients' and potential patients' choices among anaesthetics
      for periodontal recall visits.
AB  - OBJECTIVES: Dentinal hypersensitivity and recurrent disease may necessitate the
      use of anaesthetic during periodontal recall visits. However, an aversion to
      injections may affect patient compliance. The objectives of this study were to
      determine choices patients and 'potential' patients make when provided with
      information on the risks and benefits of alternative anaesthetic choices for root
      planing during periodontal recalls and to examine which factors influence these
      choices. METHODS: Using an interactive computer tool, scenarios described the
      risks and benefits of root planing during periodontal maintenance and the
      anaesthetic alternatives (no anaesthetic, an experimental thermosetting gel
      anaesthetic and traditional local infiltration anaesthesia). Compliant patients
      for whom anaesthesia was recommended during recall cleanings were recruited from
      private periodontal practices (n=97). General population subjects (potential
      patients) were recruited by random digit dialing (n=196) RESULTS: As dental
      insurance was one of the inclusion criteria, the sample was representative of a
      working population. Most subjects reported tooth sensitivity (recall 84.5%,
      general 59.9%). The majority of patients wanted some form of anaesthetic, either
      gel (recall 82.5%, general 81.0%) or local infiltration (recall 10.3%, general
      16.4%). Fifty-five percent of subjects reported moderate or severe pain from
      their previous dental injection(s). Asked if they were to have a dental needle
      tomorrow, 52.5% would be somewhat or very anxious. Of those who chose gel, 63.47%
      would be more or much more willing to return for recall visits if the gel were
      available. Using multivariate logistic regression, concern about pain and anxiety
      associated with needles were the only statistically significant characteristics
      associated with anaesthetic preference. CONCLUSIONS: Concern about pain and
      anxiety associated with needles dominates preferences for dental anaesthesia. The
      overwhelming preference for a non-injectable anaesthetic reveals a strong
      clinical need for such alternatives.

PMID- 11306159
TI  - Plaque, gingival health and post-operative sensitivity in titanium inlays and
      onlays: a randomized controlled clinical trial.
AB  - OBJECTIVES: Few clinical data on the use of titanium for restorative appliances
      are available. The aim of this study was to clinically evaluate titanium
      restorations compared to gold alloy restorations with regard to plaque, gingival
      health and post-operative sensitivity. METHODS: In 54 patients, 99 titanium
      restorations were placed. The control group comprised 56 patients with 96 high
      gold alloy restorations. The material was chosen by random. Each patient received
      one or two Class II restorations. Plaque Index (Silness and Loe, 0-3), Gingival
      Index (Loe and Silness, 0-3), and post-operative sensitivity (1-4, 1=none) were
      rated at 2 weeks, 3 months, 6 months, 12 months, and 18 months, post-operatively.
      RESULTS: The mean plaque scores ranged from 0.89 to 0.99 in the titanium group,
      and from 0.88 to 1.04 in the gold group. The mean gingival scores ranged from
      0.91 to 1.07 in the titanium group, and from 0.82 to 0.99 in the gold group. The
      mean plaque and gingival scores of the titanium and gold group did not differ
      significantly at any visit (P>0.05). To evaluate post-operative sensitivity,
      patients with one MOD restoration each were included, resulting in 46 titanium
      and 44 high gold restored teeth. Mean values of the post-operative sensitivity
      scores in the titanium group were significantly higher than in the gold group
      (P<0.05). The restoration material was found to be the dominating variable with
      regard to post-operative sensitivity, which was not influenced by age, sex and
      the application of calcium hydroxide liner. CONCLUSIONS: It is concluded that
      neither higher plaque scores nor adverse effects on gingival health are to be
      expected in titanium restorations.

PMID- 11306160
TI  - Comparison of three types of fiber-reinforced composite molar crowns on their
      fracture resistance and marginal adaptation.
AB  - Three types of fiber-reinforced composite (FRC) molar crowns were tested on their
      fracture resistance and marginal adaptation under simulated oral stress
      conditions. Two glass fiber systems, one processed with a vacuum/pressure system,
      the other by manual fiber adaptation, and a polyethylene fiber system were
      evaluated. Every group consisted of 12 crowns. All crowns were luted adhesively
      on human molars and exposed to thermal cycling and mechanical loading (TCML: 6000
      x 5 degrees C/55 degrees C; 1.2 x 10(6) x 50N; 1.66Hz). The marginal adaptation
      was evaluated through dye-penetration and analyzed semi-quantitatively with a
      scanning electron microscope. The fracture resistance was measured using a Zwick
      universal testing machine. The highest fracture resistance was observed on the
      glass-fiber systems (FibreKor/Sculpture 1875N +/- 596; Vectris/Targis 1726+/
      542), though statistically, the polyethylene system (belleGlass/Connect 1388+/
      620) was not significantly weaker. All systems exceeded the fracture resistance
      required to withstand the maximum masticatory forces expected in the molar
      region. The marginal adaptation generally had a tendency towards larger gaps
      after TCML. The crown/composite-cement bond deteriorated significantly after TCML
      with the manual fiber adaptation and the polyethylene fiber system. The
      cement/tooth bond strength depended on which composite-cement/dentin-adhesive
      system was used. CONCLUSION: The fracture resistance of molar crowns made of
      glass-fiber reinforced composite was higher than those of polyethylene fiber
      reinforced composite crowns. However, there was no statistically significant
      difference. The marginal adaptation seems to depend on the fiber systems and
      composite-cement/dentin adhesive system used.

PMID- 11306162
TI  - Effect of mixing methods on the compressive strength of glass ionomer cements.
AB  - OBJECTIVE: The purpose of the study was to evaluate the effect of the mixing
      method on the compressive strength and porosity of dental glass ionomer cements.
      METHOD: Five glass ionomer cements were chosen for use in the study. Two were
      hand mixed and three were encapsulated. The latter were mixed either by shaking
      or rotating. Following mixing by rotation some samples were centrifuged before
      use. The 24h compressive strength was determined for each cement/mixing regime
      combination and fracture surfaces were examined using SEM. RESULTS: The mixing
      method had a significant effect on compressive strength (P<0.05). For the
      luting/lining cement, hand mixing produced a significantly greater compressive
      strength (P<0.05). For the restorative cement, there were only small differences
      between specimens mixed by different methods and hand mixing gave a significantly
      lower compressive strength than mixing by rotation followed by centrifuging
      (P<0.05). Porosity was incorporated in all samples and low values of compressive
      strength were associated with larger pores. SIGNIFICANCE: The strength of glass
      ionomer cements is affected by incorporated porosity and this is dependent on the
      method of mixing. For some cements hand mixing is favoured in order to reduce
      porosity and increase strength but this is not generally applicable to all
      cements.

PMID- 11306161
TI  - The effect of acquired salivary pellicle on the surface free energy and
      wettability of different denture base materials.
AB  - OBJECTIVE: The objective of the present study was to evaluate the effect of
      salivary coating on the wettability and surface free energy of different denture
      base materials. METHODS: Five acrylic resin and two metallic denture base
      materials were investigated. Ten specimens of each material (20 x 15x1.5mm) were
      fabricated and a standardized method was used for polishing the test specimens.
      Whole unstimulated saliva was collected from a single healthy donor. The
      wettability properties of the materials were tested before and after organic
      layer formation. The wetting forces were determined according to the Wilhelmy
      Plate Technique. Diiodomethane, ethylene glycol and formamide were used as probe
      liquids. The contact angles, Lifshitz-van der Waals surface energy components,
      Lewis acid-base surface energy components and total surface energies were
      calculated using the equations described in the paper. The significance of the
      differences in the experimentally determined surface energies of different
      denture materials are calculated by statistical methods. CONCLUSIONS: Light-cured
      acrylic resin was the most wettable material with a significant basic character.
      Organic layers decreased the total surface free energies of all materials and at
      the same time imparted a more basic character. The coatings had a homogenizing
      effect in terms of the surface free energy components of the denture materials,
      nevertheless, their adhesive properties were still influenced by the substrate
      employed.

PMID- 11306163
TI  - Mineralization in bovine dentin adjacent to glass-ionomer restorations.
AB  - OBJECTIVES: To assess the uptake of fluoride as well as the increase in
      mineralization by bovine dentin after restoring an experimentally made cavity
      with conventional glass-ionomer cement or a polyacid resin composite. METHODS:
      Cylindrical cavities were prepared on the labial root surfaces in bovine dentin.
      The cavities were restored with the test material. The restored teeth were
      individually suspended in distilled water at 37 degrees C for 30 days. The teeth
      were sectioned and the superficial dentin cavity walls were analyzed for
      fluoride, calcium, and phosphorus by an EPMA device. The effects of the different
      fluoride-releasing materials on the hardness of the dentin were determined by
      indentation (20-microm intervals below the filled surface into the underlying
      sound dentin from the surface to a depth of 100microm). RESULTS: Conventional
      glass-ionomer cement had a significant effect on fluoride uptake. In addition,
      the calcium and phosphorus scan revealed the elevation of calcium and phosphorus
      levels in a deeper zone corresponding to the locations of the fluoride uptake at
      the surface of axial wall. However, the polyacid resin composite did not exhibit
      a zone of calcium and phosphorus elevation. The average dentin hardness under
      conventional glass-ionomer cement in the studied five distances ranged from 84.3
      to 61.3KHN, however, that of the polyacid resin composite ranged from 62.5 to
      64.9KHN. Analysis of variance for these data demonstrated a significant
      difference in hardness between the 20-microm depth and the other depths (P<0.01,
      ANOVA Fisher's PSLD). CONCLUSION: The present paper indicates that the fluoride
      penetrated deeper into the dentin with conventional glass-ionomer cement than the
      polyacid resin composite. Conventional glass-ionomer cement had a significant
      effect on fluoride uptake. In addition, hypermineralization occurred within the
      superficial dentin cavity wall region of conventional glass-ionomer cement.

PMID- 11306164
TI  - Fracture resistance of dentin-composite interfaces using different adhesive resin
      layers.
AB  - OBJECTIVES: The objective of this study was to study the effect of different
      adhesive layers on the interfacial fracture toughness (K(ICi)) of dentin-resin
      composite interfaces. METHODS: Miniature short-rod fracture toughness specimens
      containing a chevron-shaped dentin-bonded interface along their midplane were
      used for testing. Each interface zone contained a thinned (one coat of unfilled
      adhesive resin, air-thinned), one-layer (one coat of unfilled adhesive resin,
      brush-thinned), two-layer (two coats of unfilled adhesive resin, brush-thinned),
      10% filled or 45% filled adhesive resin layer. After storage in distilled water
      at 37 degrees C for 24h, the fracture toughness test specimens were loaded in
      tension at an extension rate of 0.5mm/min until fracture and the K(ICi) were
      determined. The results were analysed by ANOVA and Fisher's LSD test (p<0.05).
      Scanning electron microscopy was used to examine representative fracture
      surfaces. RESULTS: There were no significant differences in mean K(ICi) among the
      different unfilled adhesive resin layer groups. SEM examination of these
      specimens showed that fracture generally occurred between the resin-infiltrated
      layer and adhesive resin layer during interfacial fracture toughness testing. The
      mean K(ICi) for the 10% filled groups was not significantly different from the
      unfilled groups. The 45% filled group, however, demonstrated the highest K(ICi)
      values, the thickest adhesive resin layer under SEM examination, and a fracture
      path through the adhesive resin layer. CONCLUSIONS: There were no significant
      differences in K(ICi) when the unfilled adhesive resin was used despite different
      application methods. The 45% filled adhesive resin improved the properties of the
      dentin-composite interface with respect to both interfacial fracture resistance
      and dentinal seal after fracture.

PMID- 11306165
TI  - Effect of primers containing N-methylolacrylamide or N-methylolmethacrylamide on
      dentin bond durability of a resin composite after 5 years.
AB  - OBJECTIVES: The effect of experimental dentin primers containing N
      methylolacrylamide (MEAA) or N-methylolmethacrylamide (MEMA) on bond durability
      of a resin composite (Photo Clearfil A) with a bonding agent (Clearfil Photo
      Bond) to bovine dentin was investigated. METHODS: The etching agents were 10%
      maleic acid (10% MA), 10% phosphoric acid (10% PA) and 10% citric acid-3% ferric
      chloride (10-3 solution). Water solutions of 35% hydroxyethyl methacrylate
      (HEMA), 50% MEAA or 30% MEMA were used as dentin primers. The etched dentin was
      pre-treated with the dentin primers for 30s. The resin composite systems were
      applied in a Teflon tube positioned onto pre-treated dentin surfaces. After water
      immersion for 1 day and 5 years, the shear bond strengths were measured. The
      amounts of calcium dissolved with etching agents were measured using atomic
      absorption spectrometry. The thicknesses of hybrid layers at the dentin-resin
      interfaces treated with 6 mol/l HCl and 1% NaOCl were measured using scanning
      electron microscopy. RESULTS: The bond strengths of the specimens (Controls)
      without primers to dentin etched with 10% MA and 10-3 solution significantly
      decreased after immersion in water for 5 years (p<0.05) while other bond
      strengths did not decrease. The bond strengths of the composites to MEMA- and
      MEAA-primed dentin were significantly higher than that of the control after 1
      day, regardless of the types of etching agents (p<0.05). The 5 year bond
      strengths of the composites to HEMA-, MEMA- and MEAA-primed dentin were
      significantly higher than that of the control, regardless of the types of etching
      agents (p<0.05). The 1 day and 5 year bond strengths of the composite to MEAA
      primed dentin were significantly higher than those of the composites to HEMA
      primed dentin, regardless of the types of etching agents (p<0.05). The highest
      amount (182.3+/-8.0 microg/cm(2)) of dissolved calcium was determined for the pre
      treatment with 10% PA, followed by that (152.0+/-6.9 microg/cm(2)) with 10% MA
      and that (140.1+/-2.8 microg/cm(2)) with 10-3 solution (p<0.05). The hybrid layer
      thicknesses (approximately 1 microm) for 10-3 solution were thinner than those
      (approximately 2 microm) for others after HCl immersion. For the controls, the
      hybrid layers after NaOCl immersion become narrower or disappeared. The main
      fracture pattern of specimens was a mixture of resin-dentin interface failure and
      dentin cohesive fracture after the bond test. CONCLUSIONS: MEAA solution was more
      effective in improving the bond strength of the controls to etched dentin than
      was HEMA after 1 day and 5 years. Clearfil Photo Bond created good hybrid dentin
      layers which could resist NaOCl-attack and showed good dentin bond durability
      when dentin primers were used, regardless of the type of etching agent.

PMID- 11306166
TI  - Molecular cloning of cDNA encoding thyroid stimulating hormone beta subunit of
      bighead carp Aristichthys nobilis and regulation of its gene expression.
AB  - The complementary DNA (cDNA) encoding pituitary thyroid stimulating hormone beta
      subunit (TSH-beta) of bighead carp was cloned and regulation of its gene
      expression was investigated for understanding phylogenetic divergence and
      evolution of TSH molecule. The cDNA was obtained from bighead carp pituitary
      total RNA by reverse transcription and polymerase chain reaction. Oligonucleotide
      primers were designed from the sequence of common carp. The full length sequence
      was then obtained by 3' and 5' rapid amplification of cDNA ends (RACE). The full
      length sequence consisting of 3' and 5' untranslated regions was 585 bp long. The
      predicted amino acid sequence consisted of a signal peptide of 19 amino acid
      residues and a mature TSH beta subunit protein of 131 residues. The coding
      sequences of the cDNAs showed variable percentage homologies with those of other
      teleosts and vertebrate species. The predicted amino acid sequence shared 71%
      identity with rainbow trout and salmon, 90% with goldfish, 50% with eel and 94%
      with common carp in the mature protein region. The percentages of identity in the
      same region in comparison with bovine, porcine, rat, mouse, human and chicken
      were only 39, 42, 41, 40, 45 and 46%, respectively. TSH beta mRNA expression was
      found only in the pituitary tissue out of other tissues tested as testis, muscle,
      brain and heart. For the first time, thyrotropin releasing hormone (TRH) and
      thyroxine (T4) effects on pituitary TSH mRNA expression were tested in teleosts
      under in vitro conditions. TRH treatment on pituitary cells increased TSH beta
      mRNA level, while T4 treatment decreased TSH beta mRNA level. The present study
      provides a direct evidence, for the first time that TRH directly upregulates TSH
      beta gene expression in teleosts.

PMID- 11306167
TI  - Actions of monoclonal antibodies on the activity of human growth hormone (GH) in
      an in vitro bioassay.
AB  - An in vitro bioassay for GH was established, based on the response of the 3T3
      F442A mouse preadipocyte cell line, together with a parallel receptor-binding
      assay using the same cells. The effects of monoclonal antibodies on the
      biological activity of human GH in vitro were then explored. Antibodies that did
      not bind GH had no effect on the bioassay or on receptor binding. Antibodies EB1
      and EB2, which strongly enhance growth-promoting actions in vivo, inhibited the
      actions of human GH in the in vitro bioassay, and blocked binding of human GH to
      receptors. Antibody NA71, which weakly enhances growth promotion by human GH in
      vivo, enhanced biological activity in vitro but did not affect receptor binding.
      Thus, enhancement of the biological activity of human GH has been shown in this
      in vitro system, but the effect does not correlate completely with the
      established enhancement effects in vivo. Of the various mechanisms that have been
      proposed to explain the enhancement effect these results support the 'restriction
      hypothesis'--the idea that monoclonal antibodies may enhance GH action in vivo by
      preventing binding of GH to receptors/binding sites that are not involved in
      growth promotion.

PMID- 11306168
TI  - Estrogen and antiestrogen actions on transforming growth factorbeta (TGFbeta) in
      normal human breast epithelial (HBE) cells.
AB  - We have previously shown that estradiol (E2) increases the growth of normal human
      breast epithelial (HBE) cells and the antiestrogen 4-hydroxytamoxifen (4-OHT)
      inhibits estrogen-induced proliferation. These effects of estrogens and
      antiestrogens on proliferation have also been well documented in breast cancer
      cells. One mechanism for the antiproliferative effects of antiestrogens is the
      stimulation of TGFbeta in hormone-dependent MCF-7 and T47D cells. The role of
      this inhibitory growth factor in normal human breast cells has not been well
      studied. Accordingly, we measured the amounts of total and active TGFbeta1 and
      TGFbeta2 by specific E(max) immunoassay (EIA) in culture medium from normal
      breast cells (epithelial and fibroblasts) and from various ER- and ER+ breast
      cancer cell lines. We established that HBE cells are sensitive to the
      antiproliferative effect of TGFbetas, and studied the effect of E2 and 4-OHT,
      alone or in combination, on the secretion and activation of TGFbetas by HBE
      cells. HBE cells secrete TGFbeta1 and even more TGFbeta2, and are sensitive to
      these factors. However, in contrast to MCF-7 cells, TGFbeta secretion in normal
      breast cells is not regulated by E2 and 4-OHT.

PMID- 11306169
TI  - Expression of a single betaalpha chain protein of equine LH/CG in milk of
      transgenic rabbits and its biological activity.
AB  - Equine chorionic gonadotropin (eCG) is a heavily glycosylated glycoprotein
      composed of non-covalently linked alpha- and beta-subunits. eCG possesses the
      particularity to bind to both LH and FSH receptors in species other than horses
      and to have a prolonged plasma half-life. All these properties make it of utmost
      interest for livestock fertilization program. Up to now, the only source of eCG
      is the serum of pregnant mare. Rabbit mammary gland is considered as a system
      able to produce recombinant glycoproteins in sufficient quantity for
      pharmaceutical use. Here we described the production of a recombinant single
      betaalpha chain of eLH/CG in the milk of transgenic rabbit. The construction of a
      single-chain permits to by-pass the problem of association-dissociation of the
      subunits. This recombinant hormone is greatly expressed (21.7 mg/l) and presents
      similar in vitro LH and FSH bioactivities. However, betaalphaeLH/CG shows an
      extremely rapid clearance (approximately 10 min), which could explain the absence
      of in vivo biological activity. So the rabbit mammary gland is not appropriate
      for the production of a recombinant active eLH/CG.

PMID- 11306170
TI  - Human FSH isoforms: carbohydrate complexity as determinant of in-vitro
      bioactivity.
AB  - Differences in sialic acid content of the hormone have been considered the main
      determinant of FSH polymorphism. The aim of the present study was to investigate
      the effect of variations in the oligosaccharide structure of the intrapituitary
      human FSH (hFSH) glycosylation variants on their intrinsic biological activity.
      FSH charge isoforms obtained after chromatofocusing were further separated by
      lectin affinity chromatography [Concanavalin A (ConA), Wheat germ agglutinin
      (WGA), Lentil lectin (LcH)]. Isolated isoforms were separately tested for in
      vitro bioactivity in a rat Sertoli cell aromatization bioassay. Our results show
      that: (1) FSH microheterogeneity is due not only to variations in the sialic acid
      content of the hormone but also to differences in the internal structure of the
      carbohydrate chains, and (2) variations in the sialic acid content as well as
      differences in the complexity of the glycans determine the full biological
      expression of FSH glycosylation variants.

PMID- 11306171
TI  - Molecular cloning of preproinsulin cDNAs from several osteoglossomorphs and a
      cyprinid.
AB  - Several preproinsulin cDNAs were isolated and characterized from four members of
      the Osteoglossomorpha (an ancient teleost group); Osteoglossum bicirrhosum
      (arawana), Pantodon buchholzi (butterfly fish), Notopterus chitala (feather fin
      knife fish), Hiodon alosoides (goldeye) and Gnathonemus petersii (elephantnose).
      In addition, we isolated and characterized the preproinsulin cDNA from Catostomus
      commersoni (white sucker, as a representative of a generalized teleost). The
      comparative analysis of the sequences revealed conservation of the cystine
      residues known to be involved in the formation of the disulfide bridges, as well
      as residues involved in the hexamer formation, except for B-17 in the butterfly
      fish, the arawana and the goldeye. However, the N-terminus of the B-chain was
      very weakly conserved among the species studied. Residues known to be significant
      for maintaining receptor-binding conformation and those known to comprise the
      receptor-binding domain were all conserved, except for a conservative
      substitution at B13, aspartate substituted glutamate in the arawana, goldeye,
      butterfly fish and white sucker, and at B16, phenylalanine substituted tyrosine
      in the elephantnose. Phylogenetic analysis of the sequences revealed a
      monophyletic grouping of the osteoglossomorphs, and showed that they were not the
      most basal living teleost. Comparative sequence analysis of preproinsulins among
      the osteoglossomorphs was useful in assessment of intergroup relationship,
      relating elephantnose with the feather fin knife fish and the arawana, butterfly
      fish, and goldeye. This arrangement of species is consistent with relationships
      based on other more classical parameters, except for the goldeye which was
      assessed as being sister to all the osteoglossomorphs. The white sucker was
      grouped with the common carp and both are cyprinids.

PMID- 11306172
TI  - In vitro effect of Triac on resistance to thyroid hormone receptor mutants:
      potential basis for therapy.
AB  - Resistance to thyroid hormone (RTH) is a syndrome caused by a mutation in the
      carboxyl-terminal domain of the thyroid hormone receptor beta (TRbeta) gene.
      3,5,3'-triiodothyroacetic acid (Triac) has been used on an empirical basis to
      treat RTH but its efficacy is still controversial. In previous studies, we
      demonstrated that Triac has TR isoform- and TRE-specific effects. In this report,
      we used five natural RTH mutations of the ligand-binding domain in both TRbeta1
      and TRbeta2 isoforms for the evaluation of the effect of T3 and Triac on
      regulation of transcription and binding affinity. We show that Triac has superior
      activity on negatively and positively regulated promoters and higher binding
      affinity than T3 for a majority of TRbeta1 and TRbeta2 mutants. However, the
      difference of transcriptional activity and binding affinity between both ligands
      is less for RTH mutants than for wild type receptors. These results suggest that
      Triac could be a potential treatment for RTH patients.

PMID- 11306173
TI  - Isoform-specific regulation of vascular endothelial growth factor (VEGF) family
      mRNA expression in cultured mouse brown adipocytes.
AB  - We have shown that brown adipose tissue (BAT), a thermogenic organ in mammals,
      expresses high levels of vascular endothelial growth factor (VEGF) mRNA in
      response to exposure to cold, which may contribute to angiogenesis associated
      with cold-induced hyperplasia of this tissue. In the present study, we examined
      mRNA expression of not only VEGF, but also VEGF-B and VEGF-C, recently cloned
      VEGF isoforms, in vitro using immortal brown adipocytes (HB2) isolated from mouse
      BAT. HB2 preadipocytes expressed detectable levels of VEGF, VEGF-B and VEGF-C
      mRNA, but a low level of VEGF. After HB2 cells differentiated into adipocytes,
      the VEGF mRNA level increased without a noticeable change in the VEGF-B and VEGF
      C mRNA levels. When HB2 cells were stimulated by norepinephrine, the VEGF mRNA
      level increased without a change in that of VEGF-B, while the VEGF-C mRNA level
      decreased. A marked reduction of VEGF-C mRNA expression was also found when HB2
      cells were treated with agonists of peroxisome proliferator-activated receptor
      gamma (PPARgamma, troglitazone), retinoic acid receptor (RAR, all-trans retinoic
      acid) and retinoid X receptor (RXR, 9-cis retinoic acid). These results suggest a
      specific adrenergic mechanism for up-regulation of VEGF expression different from
      those for other VEGF isoforms, and thereby the major contribution of VEGF to the
      cold-induced angiogenesis in BAT. In addition, the agonists of PPARgamma, RAR and
      RXR are suggested to be inhibitory to angiogenesis through the reduction of VEGF
      C production.

PMID- 11306174
TI  - Stage-specific modification of G protein beta subunits in rat placenta.
AB  - We previously analysed the plasma membrane proteins of rat placenta and prepared
      a database of 150 plasma membrane proteins, expressed in a stage-specific manner,
      utilizing two-dimensional gel electrophoresis (2D/E) [Mol. Cell. Endocrinol.
      115(1995)149]. In this study, we focused on the proteins, tentatively named psL-I
      (MW 36.2 kDa, pI 5.3) and psL-II (35.9 kDa, 5.3), which were expressed mainly in
      late pregnancy. Close to psL-I and psL-II on 2D/E gels, we also recognized more
      abundant proteins [psC-I (36.2 kDa, 5.4) and psC-II (35.9 kDa, 5.4),
      respectively] arranged side by side with the same MW but different pI. Expression
      of psL-I and psL-II was detected only in junctional zone of placenta, whereas psC
      I and psC-II were expressed in both labyrinth and junctional zones. In addition,
      psL-I and psL-II began to increase on day 16 of pregnancy and peaked at term,
      whereas expression of psC-I and psC-II was relatively constant. The analysis of
      these four proteins (psL-I, psL-II, psC-I and psC-II) by preparative 2D/E,
      peptide mapping, amino acid sequence and mass spectrometry (MALDI-TOF-MS)
      revealed that psC-I was a G protein beta1 subunit, and psC-II was a beta2
      subunit, and showed that psL-I and psL-II were molecular modified forms of psC-I
      and psC-II, respectively. Expression of these G protein beta subunits (psL-I, psL
      II, psC-I and psC-II) was also observed in rat choriocarcinoma cells, Rcho-1
      cells. Expression of psC-I and psC-II was much higher than those of psL-I and psL
      II, and their level was relatively constant regardless of the stage of
      differentiation in vitro. Interestingly, expression of psL-I and psL-II gradually
      increased in association with the differentiation. Since the expression of beta1
      and beta2 subunit proteins and their mRNAs was constant during the process of
      differentiation in Rcho-1 cells, the expression of these lower pI forms of G
      protein subunits (psL-I and psL-II) was thought to be post-translationally
      regulated. In conclusion, there are modified forms of G protein beta1 and beta2
      subunits, in the placenta and Rcho-1 cells, which are expressed in a pregnancy
      stage or differentiation stage specific manner.

PMID- 11306175
TI  - The role of nitric oxide in the biological activity of prolactin in the mouse
      mammary gland.
AB  - In mouse mammary epithelial cells, prolactin transiently elevates nitric oxide
      (NO) to a maximum of 6 nmol/mg protein at 15 min, after which levels fall
      rapidly. This stimulation can be achieved by as little as 100 ng prolactin/ml and
      can be mimicked by 100 microg sodium nitroprusside/ml. NO is both necessary and
      sufficient to mediate the prolactin-induced redistribution of its receptor from
      internal pools to the cell surface. NO can also enhance DNA synthesis stimulated
      by submaximal prolactin concentrations (50 ng/ml), but it is not necessary at
      pharmacological prolactin concentrations (1 microg/ml). In contrast, NO
      completely inhibits alpha-lactalbumin production. In summary, prolactin
      transiently elevates NO to enhance DNA synthesis and suppress premature
      differentiation; thereafter, NO declines, DNA synthesis ceases and
      differentiation proceeds. This data suggest that NO may mediate some of the
      effects of prolactin on growth in the mammary gland.

PMID- 11306176
TI  - Differential expression of activin/inhibin subunit and activin receptor mRNAs in
      normal and neoplastic ovarian surface epithelium (OSE).
AB  - Ovarian surface epithelium (OSE) is the tissue of origin for the majority of
      ovarian cancers. The mechanism underlying the neoplastic transformation of OSE to
      ovarian cancer is poorly understood. Activin, a member of the transforming growth
      factor-beta superfamily, has been shown to increase cell proliferation in ovarian
      cancer cells. The present study was carried out to investigate the expression and
      regulation of activin/inhibin subunits and activin receptors in normal and
      neoplastic OSE. Using reverse transcriptase-polymerase chain reaction and
      Southern blot analysis, the mRNA levels of alpha, betaA and betaB subunits and
      activin receptor type IIA and IIB were analyzed in normal OSE and the ovarian
      cancer cell line, OVCAR-3 cells. The alpha and betaA subunits were highly
      expressed in normal OSE when compared to OVCAR-3 cells. By contrast, betaB
      subunit was highly expressed in OVCAR-3 cells, when compared to normal OSE cells.
      Interestingly, activin receptor IIB mRNA levels were significantly higher in
      OVCAR-3 when compared to normal OSE cells, whereas activin receptor IIA mRNA
      levels were the same in both cell types. To characterize the growth modulatory
      role of activin during neoplastic progression, normal OSE and OVCAR-3 cells were
      treated with recombinant human activin A (rh-activin A). At concentrations of
      1,10 and 100 ng/ml, rh-activin A stimulated the growth of OVCAR-3 cells, but not
      of normal OSE. Treatment with follistatin, binding protein of activin, attenuates
      the stimulatory effect of activin. To determine whether the growth stimulatory
      action of activin in the neoplastic OSE is mediated via an autocrine regulatory
      mechanism, OVCAR-3 cells were treated with rh-activin A in a dose- and time
      dependent manner and the expression levels of activin/inhibin subunits and
      activin receptors were investigated. Treatments with activin increased the alpha
      and betaA subunit mRNA levels in a dose- and time-dependent manner. However, no
      difference was observed in levels of betaB subunit, or in activin receptor type
      IIA and IIB mRNAs following activin treatments in OVCAR-3 cells. Taken together,
      these results suggest that different levels of activin/inhibin and activin
      receptor isoforms are expressed in normal and neoplastic OSE cells. In addition,
      the altered expression of the activin/inhibin subunits, as well as the cell
      proliferative effect of activin observed in OVCAR-3 but not in normal OSE cells,
      indicate that activin may act as an autocrine regulator of neoplastic OSE
      progression.

PMID- 11306177
TI  - Temporal and spatial distribution of corticosteroidogenic enzymes
      immunoreactivity in developing human adrenal.
AB  - Steroid hormones secreted by fetal adrenocortical cells are considered to be a
      requirement for a fetus to maintain intrauterine life, but, to date, the
      regulation of steroid hormone secretion has not been studied in detail in the
      human fetal adrenal gland. In this study, we examined the immunolocalization of
      steroidogenic enzymes and their local regulation, including adrenal 4-binding
      protein (Ad4BP or NR5A1), steroidogenic acute regulatory protein (StAR), P450
      cholesterol side-chain cleavage (P450scc or CYP11A1), P450 17alpha
      hydroxylase/17,20-lyase (P450c17 or CYP17), 3beta-hydroxysteroid
      dehydrogenase/isomerase (3beta-HSD), P450 21 hydroxylase (P450c21 or CYP21),
      dehydroepiandrosterone sulfotransferase (DHEA-ST), P450 oxidoreductase and
      cytochrome b5, in the human fetal adrenal gland (n=31) obtained from fetuses
      ranging in ages from 14 to 40 weeks of gestation. Ad4BP immunoreactivity was
      detected in all adrenocortical zones throughout gestation, suggesting that this
      nuclear protein is likely to be essential in the development of the human
      adrenal. Immunoreactivity for StAR, P450scc, P450c21, P450 oxidoreductase and
      cytochrome b5 was detected only in fetal and transitional zone between 14 and 22
      weeks of gestation, but was detected in all three zones after 23 gestational
      weeks. 3beta-HSD immunoreactivity was not detected in any of the three cortical
      zones prior to 22 weeks of gestation, but became discernible in the transitional
      zone and definitive zone after 23 weeks. Immunoreactivity for P450c17 and DHEA-ST
      was detected in the transitional and fetal zones throughout gestation, but not in
      the definitive zone. These results suggest that the human adrenal cortex may
      produce dehydroepiandrosterone (DHEA) in the transitional and fetal zones
      throughout gestation, and cortisol in the transitional zone after the 23rd week
      of gestation.

PMID- 11306178
TI  - Insulin-like growth factor (IGF)-binding protein-6 inhibits IGF-II-induced but
      not basal proliferation and adhesion of LIM 1215 colon cancer cells.
AB  - IGF-II is an autocrine growth factor for many colon cancer cells. This study
      aimed to determine the role of IGF-II in proliferation and adhesion of LIM 1215
      colon cancer cells. RT-PCR demonstrated expression of IGF-I and IGF-II mRNA.
      Addition of IGF-I or -II increased monolayer proliferation in a dose-dependent
      manner. Although addition of IGFBP-6 had no effect on basal proliferation,
      coincubation of IGFBP-6 decreased IGF-II but not IGF-I-induced proliferation.
      Colony formation in agar was increased by IGF-II, an effect inhibited by
      coincubation with IGFBP-6. IGFBP-6 alone significantly decreased colony
      formation. Preincubation of cells with IGF-II increased adhesion to type IV
      collagen, fibronectin and laminin. IGFBP-6 had no effect on basal cell adhesion
      but completely inhibited the effects of IGF-II. LIM 1215 colon cancer cells are
      therefore IGF-responsive but IGF-II is not a major autocrine factor for these
      cells in monolayer, suggesting heterogeneity between colon carcinoma cell lines
      with respect to the role of the IGF system.

PMID- 11306179
TI  - The distribution of neuropeptide Y gene expression in the chicken brain.
AB  - Neuropeptide Y (NPY) is demonstrated to play an important role in central control
      of voluntary feed intake (FI) of a variety of species. The commercial broiler
      chicken has been intensively selected over generations for increased body weight,
      achieved largely through increased FI. This has resulted in a contemporary animal
      that does not regulate FI to maintain energy balance, and represents a model for
      hyperphagia and obesity if allowed unrestricted access to feed. In the present
      study, the distribution of NPY mRNA was mapped in the brain of juvenile, broiler
      strain chicken, and results interpreted in the context of previous data for
      strains that do not exhibit hyperphagia. NPY mRNA was widely distributed in the
      broiler brain, and highly expressed in the hippocampus, nucleus commissurae
      pallii, infundibular hypothalamic nucleus, nucleus pretectalis pars ventralis and
      neurons around the nucleus rotundus. Moderately labeled neurons were found in the
      lateral septal organ, nucleus periventricularis hypothalamus and nucleus
      paraventricularis magnocellularis. The pallium exhibited only sparse labeling.
      Generally, the distribution of cell groups expressing NPY mRNA was consistent
      with those regions exhibiting NPY immunoreactivity, and also matches the
      distribution of receptor binding sites reported in the literature for the chicken
      brain. This suggests that NPY may be involved in functions controlled by these
      regions. The observation of NPY gene expression in brain regions involved in
      appetite regulation is consistent with the recognized importance of NPY in FI
      regulation in a variety of species, and with the chronic hyperphagia,
      characteristic of the broiler.

PMID- 11306180
TI  - Ontogeny of the neurosteroid enzyme Cyp7b in the mouse.
AB  - The function of the major adrenal steroid dehydroepiandrosterone (DHEA) is not
      known. It has been reported to improve learning and memory in mice and can exert
      neuroprotective and trophic effects, particularly in the hippocampus. We recently
      described a cytochrome P450 (Cyp7b), that catalyses the 7alpha-hydroxylation of
      DHEA and related steroids and sterols. In this paper, we have used mRNA in situ
      hybridisation to map the ontogeny of cyp7b in the foetal and adult mouse. Cyp7b
      mRNA is highly expressed throughout from embryonal (E) day 12.5 (the earliest day
      studied). There is also expression throughout the body, including the spine,
      thymus, developing kidneys, lungs and urogenital region. Widespread expression
      becomes more restricted towards birth: in newborn mice expression is largely
      limited to the hippocampus, with some expression being detected in kidney. The
      overall decline in mRNA, and increasing restriction to the hippocampus, is
      reflected in the DHEA hydroxylation activity of brain homogenates. This pattern
      of cyp7b mRNA expression in specific organs could be consistent with a protective
      role in foetal development, with highest expression seen when the foetus is most
      vulnerable to steroid excess (i.e.) early gestation.

PMID- 11306181
TI  - Dynamic changes in stanniocalcin gene expression in the mouse uterus during early
      implantation.
AB  - Blastocyst implantation is accompanied by dramatic changes in gene expression to
      facilitate decidualization and remodelling of uterine architecture. Stanniocalcin
      (STC) is a new mammalian polypeptide hormone with roles in ion transport,
      reproduction and development. Here we report dynamic changes in STC mRNA and
      protein distributions in the early post-implantation mouse uterus. In the non
      pregnant state, STC gene expression was confined to the uterine lumenal
      epithelium. Following implantation STC gene expression shifted to mesometrial
      stromal cells bordering the uterine lumen. Between E6.5-E8.5 expression shifted
      once more to cells of the mesometrial lateral sinusoids, and then declined
      thereafter. Intriguingly immunoreactive STC did not entirely co-localize with
      areas of high STC gene activity and instead appeared to accumulate in presumptive
      targets of the hormone (uterine epithelium, stromal and decidual cells,
      trophoblastic giant cells). STC is only the fourth gene identified as being
      expressed mesometrially in the uterus following implantation.

PMID- 11306182
TI  - Estrogen response element sequence impacts the conformation and transcriptional
      activity of estrogen receptor alpha.
AB  - Estrogens play a critical role in mammary gland development, bone homeostasis,
      reproduction, and the pathogenesis of breast cancer by activating estrogen
      receptors (ERs) alpha and beta. Ligand-activated ER stimulates the expression of
      target proteins by interacting with specific DNA sequences: estrogen response
      elements (EREs). We have demonstrated that the ERE sequence and the nucleotide
      sequences flanking the ERE impact ERalpha binding affinity and transcriptional
      activation. Here, we examined whether the sequence of the ERE modulates ERalpha
      conformation by measuring changes in sensitivity to protease digestion. ERalpha,
      occupied by estradiol (E2) or 4-hydroxytamoxifen (4-OHT), was incubated with
      select EREs and digested by chymotrypsin followed by a Western analysis with
      antibodies to ERalpha. ERE binding increased the sensitivity of ERalpha to
      chymotrypsin digestion. We found both ligand-specific and ERE-specific
      differences in ERalpha sensitivity to chymotrypsin digestion. The ERE-mediated
      increase in ERalpha sensitivity to chymotrypsin digestion correlates with E2
      stimulated transcriptional activity from the same EREs in transiently transfected
      cells. Transcriptional activity also correlates with the affinity of ERalpha-ERE
      binding in vitro. Our results support the hypothesis that the ERE sequence acts
      as an allosteric effector, altering ER conformation. We speculate that ERE
      induced alterations in ERalpha conformation modulate interaction with co
      regulatory proteins.

PMID- 11306183
TI  - Cytokines and the central nervous system.
AB  - Cytokines are involved both in the immune response and in controlling various
      events in the central nervous system, that is, they are equally immunoregulators
      and modulators of neural functions and neuronal survival. On the other hand,
      cytokine production is under the tonic control of the peripheral and the central
      nervous system and the cytokine balance can be modulated by the action of
      neurotransmitters released from nonsynaptic varicosities [131]. The neuroimmune
      interactions are therefore bidirectional-cytokines and other products of the
      immune cells can modulate the action, differentiation, and survival of neuronal
      cells, while the neurotransmitter and neuropeptide release play a pivotal role in
      influencing the immune response. Cytokines and their receptors are constitutively
      expressed by and act on neurons in the central nervous system, in both its normal
      and its pathological state, but cytokine overexpression in the brain is an
      important factor in the pathogenesis of neurotoxic and neurodegenerative
      disorders. Accordingly, it can be accepted that the peripheral and central
      cytokine compartments appear to be integrated, and their effects might synergize
      or inhibit each other; however, it should always be taken into account that they
      are spatiotemporally differentially regulated. New concepts are reviewed in the
      regulation of relations between cytokine balance and neurodegeneration, including
      intracellular receptor-receptor, cell-cell, and systemic neuroimmune interactions
      that promote the further elucidation of the complexities and cascade of the
      possible interactions between cytokines and the central nervous system.

PMID- 11306184
TI  - Ovulation delay induced by blockade of the cholinergic system on dioestrus-1, is
      related to changes in dopaminergic activity of the preoptic anterior-hypothalamic
      area of the rat.
AB  - One hour after the injection of 100 mg/kg of atropine-sulphate at 1300 h of
      dioestrus-1, there was an abrupt increase of 17beta-oestradiol plasma level and a
      significant increase in dopaminergic neural activity in preoptic anterior
      hypothalamic area, without changes in luteinizing hormone serum level, in
      comparison with the saline injected group. Animals injected with atropine
      sulphate showed a second increase in dopaminergic neural activity in the preoptic
      anterior-hypothalamic at 1100 of dioestrus-2 (atropine-sulphate 0.471 +/- 0.7 vs.
      saline 0.241 +/- 0.03, p < 0.01). In this group of animals, the preovulatory
      surges of 17beta-oestradiol and luteinizing hormone occurred simultaneously at
      1700 h of the expected day of oestrus; spontaneous ovulation was delayed until
      the expected day of dioestrus-1. Present results suggest that during dioestrus-1
      there is a functional relationship between the cholinergic and dopaminergic
      systems in preoptic anterior-hypothalamic area, regulating the release of
      luteinizing hormone resulting in ovulation.

PMID- 11306185
TI  - Changes in monoaminergic activity in the anterior, medium and posterior
      hypothalamus, gonadotropins levels and ovarian hormones during puberty of the
      female rat.
AB  - The aim of present study is the analysis of monoamines concentrations changes in
      the anterior, medium and posterior hypothalamus, as well as changes in serum
      gonadotropins levels, ovarian steroids and follicular growth during the
      prepubertal development of the female rat. Noradrenergic activity in the
      anterior, medium and posterior hypothalamus reached highest level at day 13 after
      birth, followed by a subsequent decrease from day 15 to 19 and an increase on
      days 22 and 27 postnatal. At day 1, neural activity in the medium hypothalamus
      was higher than the activity in the anterior and posterior hypothalamus.
      Serotoninergic activity in three portions of the hypothalamus was higher
      throughout the prepubertal development. Follicle-stimulating hormone and
      luteinizing hormone serum levels increased between days 11 and 17 and decreased
      from day 19 to 36. The concentration of 17beta-estradiol was consistently low
      throughout the prepubertal development and increased at day 39 after birth. These
      results indicate that during the prepubertal development of the rat, the three
      regions of the hypothalamus show significant changes in the monoaminergic neural
      activity. There is an inverse relationship between the noradrenergic activity on
      the anterior and medium hypothalamus and serotoninergic activity in the posterior
      hypothalamus with ovarian steroids during sexual maturation. These changes may be
      linked to the development of the neuroendocrine processes that modulate
      gonadotropin secretion and ovarian function.

PMID- 11306186
TI  - Glial reaction to volkensin-induced selective degeneration of central neurons.
AB  - Volkensin, a highly toxic protein retrogradely transported through axons, was
      used to target primary neuronal death in brainstem precerebellar relays after
      injection in the cerebellar cortex of rats. The reaction of astrocytes and
      microglia was studied with immunohistochemistry in the inferior olivary and
      pontine nuclei from 6 h to 14 days. Neurodegenerative features were evident since
      the first hours, especially in the pontine nuclei, and neuronal loss reached a
      plateau at 7 days in the inferior olive and at 10 days in the pons. Astrocytic
      activation, revealed by glial fibrillary acidic protein immunoreactivity, was
      concomitant with early signs of neuronal death and gradually increased. Microglia
      activation, revealed by OX-42 immunoreactivity, was evident at 2 days and became
      rapidly intense in precerebellar relays. At 1 week, marked ED-1 immunoreactivity
      also revealed phagocytic features of microglia, which persisted during the second
      week. In addition, major histocompatibility complex antigens (MHC) class I and II
      were induced in cells exhibiting microglial features. In the inferior olive, MHC
      I immunoreactivity was evident since 4 days and persisted at 14 days, whereas MHC
      II induction was intense at 7 days and subsided at 2 weeks. In the pontine nuclei
      high expression of both MHC antigens persisted instead at 14 days, probably
      reflecting the progression of neuronal death. Thus, targeted lethal injury of
      central neurons elicited prompt activation of both astrocytes and microglia; the
      marked microglia activation resulted in phagocytic features and immunophenotypic
      changes, with a temporal regulation that paralleled the evolution of
      neurodegenerative phenomena.

PMID- 11306187
TI  - Stimuli that induce a cholinergic neuronal phenotype of NG108-15 cells upregulate
      ChAT and VAChT mRNAs but fail to increase VAChT protein.
AB  - The vesicular acetylcholine transporter (VAChT) and choline acetyltransferase
      (ChAT) are encoded by genes organized in a single gene locus, and coregulation of
      the transcription of the two genes has been repeatedly reported in cholinergic
      tissues. In the present study, different stimuli were used to induce the
      differentiation of the hybridoma cells NG108-15 and we examined their effects on
      the modulation of VAChT and ChAT expression at the mRNA and protein levels. All
      agents upregulated the VAChT and ChAT mRNA levels, but to a different extent.
      ChAT activity was increased by retinoic acid, dexamethasone, and dibutyrylcyclic
      AMP (dbcAMP), and a synergistic effect was observed with a combined dexamethasone
      and dbcAMP treatment. Nonetheless, no changes in the VAChT protein level could be
      observed, as judged from ligand binding studies as well as from immunochemical
      detection. Hemicholinium-3-sensitive choline uptake, hemicholinium-3 binding, and
      acetylcholine content were increased by differentiating agents, with a rank order
      of potency comparable to their effects on ChAT activity. Prominent changes were
      observed in the expression of vesicular protein markers, particularly with the
      associated treatment dexamethasone and dbcAMP. Thus, it appears that although the
      different stimuli we have been using are able to stimulate neuronal features and
      activate the transcription of cholinergic genes, they did not contrive to
      increase the level of VAChT protein in these cells.

PMID- 11306188
TI  - Neurochemical phenotype of sympathetic nervous system outflow from brain to white
      fat.
AB  - The sympathetic innervation of white adipose tissue (WAT) appears to be a
      dominant mechanism triggering lipolysis. The purpose of this study was to
      determine the neurochemical phenotype of neurons comprising the sympathetic
      outflow from brain to WAT. This was accomplished by injecting Siberian hamster
      WAT with a viral retrograde transneuronal tract tracer, the pseudorabies virus
      (PRV), in combination with immunocytochemical characterization of several
      neurotransmitters or their synthetic enzymes in the brain. Catecholaminergic
      (tyrosine hydroxylase [TH] and dopamine-beta-hydroxylase [DBH] immunoreactivity)
      and peptidergic (arginine vasopressin [AVP] and oxytocin [OXY] immunoreactivity)
      neurons were part of this outflow, but the percentage of double-labeled cells was
      small, consistent with previous studies. Brainstem PRV + TH- or PRV + DBH-labeled
      cells were in previously identified noradrenergic areas (A5, A6, and
      subcoeruleus, rostroventrolateral medulla [RVL], some reticular nuclei).
      Forebrain double labeling was greatest in the paraventricular (TH, AVP, OXY) and
      suprachiasmatic (AVP) nuclei, both implicated in the central control of
      lipolysis. Differences between the PRV double labeling reported here for WAT
      versus that of other sympathetic peripheral targets were PRV + DBH in A5 and RVL,
      and PRV + TH in RVL and in the lateral paragigantocellular and lateral reticular
      nuclei. Collectively, these results begin to identify the neurochemical identity
      of the sympathetic outflow from brain to WAT.

PMID- 11306189
TI  - Hypercapnia stimulates prostaglandin E(2) but not prostaglandin I(2) release in
      endothelial cells cultured from microvessels of human fetal brain.
AB  - Hypercapnia-induced cerebral vasodilation involves prostanoids, in newborns. The
      source of these prostanoids, however, is not yet determined. In the present study
      we address the hypothesis that microvascular endothelial cells of human fetal
      cerebrum increase the synthesis of dilator prostanoids in response to high
      pCO(2). Cells were isolated from a 22-week-old human fetus. Indication of induced
      abortion was 46 XY-t(3,10) 3q-25 chromosome abnormality. Normocapnia or
      hypercapnia was performed during normoxic and normothermic conditions in the
      medium of the cell culture. After normocapnic or hypercapnic stimuli, the amounts
      of released prostaglandin E(2) and 6-keto-prostaglandin F(1alpha) (the stable
      metabolite of prostaglandin I(2)) were measured by radioimmunoassay. Endothelial
      cells cultured from human fetal brain microvessels express PGE(2) and 6-keto
      PGF(1alpha) in different degrees. Hypercapnic stimulus induced a significant
      increase of PGE(2), while expression of 6-keto-PGF(1alpha) was not augmented by
      the same stimulus. PGE(2) of endothelial origin, therefore, could be a factor in
      the mediation of the hypercapnia-induced vasodilation in human fetuses.

PMID- 11306190
TI  - Effects of intraplantar injection of carrageenan on central dopamine release.
AB  - The present study examined the changes of extracellular concentration of dopamine
      and its metabolite homovanillic acid in the striatum, the periaqueductal gray and
      the dorsal horn of lumbar spinal cord following intraplantar injection of
      carrageenan. In vivo microdialysis and high-performance liquid chromatography
      with electrochemical detection were performed. The results showed that
      intraplantar injection of carrageenan significantly increased dopamine or
      homovanillic acid levels in the different central regions. The present study
      suggested that the central dopamine system (at least including ascending
      nigrostrialtal pathway and descending A11--the dorsal horn fibers) be activated
      following the carrageenan, while the activation probably mediated
      antinociception.

PMID- 11306191
TI  - The inhibitory effect of serotonin on the spontaneous discharge of
      suprachiasmatic neurons in hypothalamic slice is mediated by 5-HT(7) receptor.
AB  - The effects of serotonin (5-HT) receptor agonists and antagonists on the
      spontaneous discharge of suprachiasmatic nucleus (SCN) neurons were investigated
      using rat hypothalamic slice. It was found that: (1) the SCN neurons showed a
      persistent rhythm in the spontaneous discharge rate, which was higher during the
      light phase than during the dark phase; (2) the effects of 5-HT on SCN neurons
      was inhibitory in nature and the sensitivity of SCN neurons to 5-HT during the
      light phase was lower than that during the dark phase; (3) both 5-HT and 5
      HT(1/7) receptor agonist, (+/-)-8-hydroxy-2-(DL-N-propylamino) tetralin
      hydrobromide, could inhibit the spontaneous discharge of SCN neurons. This
      inhibitory effect could be blocked by 5-HT(2/7) receptor antagonist ritanserin
      and putative 5-HT(7) receptor antagonists clozapine, but neither by selective 5
      HT(2) receptor antagonist ketanserin, nor by 5-HT(1) receptor antagonist
      pindolol. It was suggested that the inhibitory effect of 5-HT on the spontaneous
      discharge of SCN neurons in rat hypothalamic slice is mediated by 5-HT(7)
      receptor subtype.

PMID- 11306192
TI  - Tecto-isthmo-optic transmission in pigeons is mediated by glutamate and nitric
      oxide.
AB  - The isthmo-optic nucleus of the centrifugal system in birds receives primarily
      input from the ipsilateral tectum and projects to the contralateral retina. The
      present study using brain slices and microiontophoresis shows that synaptic
      transmission from the tectum to the centrifugal nucleus in pigeons is excitatory.
      About 75% of tecto-isthmo-optic fibers are glutamatergic, mediated by alpha-amino
      3-hydroxy-5-methyl-4-isoxazole propionic acid but not N-methyl-D-aspartate
      receptors, and 25% of others may use nitric oxide as a transmitter or modulator.
      On the other hand, about 60% of isthmo-optic cells receive glutamatergic
      afferents, 20% receive nitric oxidergic afferents, and 20% of others receive both
      glutamatergic and nitric oxidergic afferents from the tectum. In the last group,
      it is more likely that both glutamate and nitric oxide may co-release from the
      same tecto-isthmo-optic terminals. All the isthmo-optic cells examined in the
      present study also receive gamma-aminobutyric acid (GABA)ergic afferents via
      GABA(A) and GABA(B) receptors probably from some extratectal structures.

PMID- 11306193
TI  - Alpha-spectrins are major ubiquitinated proteins in rat hippocampal neurons and
      components of ubiquitinated inclusions in neurodegenerative disorders.
AB  - We have demonstrated that alpha-spectrins (alphaSpISigma* and alphaSpIISigma1)
      are major ubiquitinated proteins in terminally differentiated hippocampal neurons
      in culture. Western blotting experiments, using alphaSpISigma1, alphaSpIISigma1,
      and ubiquitin antibodies and lysates of 11-day-old cultured rat hippocampal
      neurons, have demonstrated that a single band comigrating with alphaSpISigma* and
      alphaSpIISigma1 in a 5% polyacrylamide sodium dodecyl sulfate gel is recognized
      by ubiquitin antibodies when (125)I-protein A is used for detection.
      Immunofluorescence staining of the 7- and 12 -day-old rat hippocampal neuron
      cultures using ubiquitin, alphaSpISigma1, and alphaSpIISigma1 antibodies
      demonstrated that all of these antibodies label neurons but not the astrocytes in
      the cultures. Immunoprecipitation of spectrin subunits in lysates of 12-day-old
      rat hippocampal neurons under stringent conditions (9.5 M urea) using
      alphaSpISigma1 and alphaSpIISigma1 antibodies followed by Western blot
      experiments of the immunoprecipitated spectrin subunits using alphaSpISigma1,
      alphaSpIISigma1 and ubiquitin antibodies confirmed that both alphaSpISigma* and
      alphaSpIISigma1 are ubiquitinated in rat hippocampal neurons. Furthermore, we
      demonstrated by immunohistochemistry that alpha-spectrins are components of the
      cytoplasmic ubiquitinated inclusions in hippocampal neurons in Alzheimer's and
      Parkinson's disease patients.

PMID- 11306194
TI  - Characteristics of protective effects of NMDA antagonist and calcium channel
      antagonist on ischemic calcium accumulation in rat hippocampal CA1 region.
AB  - Effects of excitatory amino acid receptor antagonists and voltage-dependent
      Ca(2+) channel antagonists on ischemia-induced intracellular free Ca(2+)
      accumulation in rat hippocampal slices were examined. Ischemia caused a large
      Ca(2+) accumulation in CA1 region but a small Ca(2+) accumulation in CA3 and
      dentate gyrus regions. When applied during ischemia, the NMDA receptor antagonist
      MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine
      maleate) inhibited the ischemic Ca(2+) accumulation only in the CA1, but the non
      NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) inhibited it
      in all the three regions. The L-type Ca(2+) channel antagonists nifedipine and
      verapamil inhibited the ischemic Ca(2+) accumulation only in the CA1 region, but
      omega-conotoxin, a N- and L-type Ca(2+) channel antagonist inhibited the Ca(2+)
      accumulation in all the three regions of the hippocampus. When applied after 5
      min ischemia, nifedipine but not MK-801, inhibited sustained postiscehmic Ca(2+)
      elevation in the CA1 region but not in the CA3 and dentate gyrus regions. These
      findings suggest that the enhanced ischemia-induced Ca(2+) accumulation in the
      CA1 region is mediated via activation of both NMDA receptors and L-type-like
      Ca(2+) channels. It appears that sustained postischemic Ca(2+) elevation in the
      CA1 region is mediated via activation of L-type-like Ca(2+) channels, but not of
      NMDA receptors.

PMID- 11306195
TI  - Activation of the subfornical organ enhances extracellular noradrenaline
      concentrations in the hypothalamic paraventricular nucleus in the rat.
AB  - Experiments were carried out to investigate whether angiotensinergic efferent
      pathways from the subfornical organ (SFO) regulate the noradrenergic system in
      the region of the hypothalamic paraventricular nucleus (PVN). Intracerebral
      microdialysis techniques were utilized to quantify the extracellular content of
      noradrenaline (NA) in the PVN area. In urethane-anaesthetized male rats,
      electrical stimulation (5-20 Hz, 600 microA) of the SFO significantly increased
      the NA concentration in the region of the PVN, and the increase was significantly
      prevented by pretreatment with the angiotensin II (ANG II) antagonist saralasin
      (Sar, 5 microg), into the third ventricle (3V). Injections of ANG II (5 microg)
      into the 3V significantly enhanced NA release in the PVN area. These results
      suggest that the angiotensinergic pathways from the SFO to the PVN may act to
      enhance NA release in the region of the PVN.

PMID- 11306196
TI  - Brain electrical microstates in subjects with panic disorder.
AB  - Brain electrical microstates represent spatial configurations of scalp recorded
      brain electrical activity and are considered to be the basic elements of stepwise
      processing of information in the brain. In the present study, the hypothesis of a
      temporo-limbic dysfunction in panic disorder (PD) was tested by investigating the
      topographic descriptors of brain microstates, in particular the one corresponding
      to the Late Positive Complex (LPC), an event-related potential (ERP) component
      with generators in these regions. ERPs were recorded in PD patients and matched
      healthy subjects during a target detection task, in a central (CC) and a lateral
      condition (LC). In the CC, a leftward shift of the LPC microstate positive
      centroid was observed in the patients with PD versus the healthy control
      subjects. In the LC, the topographic descriptor of the first microstate showed a
      rightward shift, while those of both the second and the fourth microstate,
      corresponding to the LPC, revealed a leftward shift in the PD patients versus the
      healthy control subjects. These findings indicate an overactivation of the right
      hemisphere networks involved in early visual processing and a hypoactivation of
      the right hemisphere circuits involved in LPC generators in PD. In line with this
      interpretation, the abnormal topography of the LPC microstate, observed in the
      CC, was associated with a worse performance on a test exploring right temporo
      hippocampal functioning. Topographical abnormalities found for the LPC microstate
      in the LC were associated with a higher number of panic attacks, suggesting a
      pathogenetic role of the right temporo-hippocampal dysfunction in PD.

PMID- 11306197
TI  - Deficient energy metabolism is associated with low free magnesium in the brains
      of patients with migraine and cluster headache.
AB  - We used phosphorus magnetic resonance spectroscopy to assess in vivo the brain
      cytosolic free magnesium concentration and the free energy released by the
      reaction of adenosine triphosphate (ATP) hydrolysis (DeltaG(ATPhyd)), the latter
      being an index of the cell's bioenergetics condition. We studied 78 patients with
      migraine in attack-free periods (7 with migraine stroke, 13 with migraine with
      prolonged aura, 37 with migraine with typical aura or basilar migraine, and 21
      with migraine without aura), and 13 patients with cluster headache. In the
      occipital lobes of all subgroups of migraine and in cluster headache patients
      cytosolic free [Mg(2+)] as well as the free energy released by the reaction of
      ATP hydrolysis were significantly reduced. Among migraine patients, the level of
      free energy released by the reaction of ATP hydrolysis and the cytosolic free
      [Mg(2+)] showed a trend in keeping with the severity of clinical phenotype, both
      showing the lowest values in patients with migraine stroke and the highest in
      patients with migraine without aura. These results support our current hypothesis
      that the reduction in free [Mg(2+)] in tissues with mitochondrial dysfunction is
      secondary to the bioenergetics deficit, and are against a primary role of low
      brain cytosolic free [Mg(2+)] in causing the bioenergetics deficit in headache.

PMID- 11306198
TI  - Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery
      and brain following intraperitoneal administration of bacterial
      lipopolysaccharide.
AB  - Gram-negative bacteria-derived lipopolysaccharide (LPS or endotoxin) is known to
      play an important role in immune and neurological manifestations during bacterial
      infections. LPS exerts its effects through cytokines, and peripheral or brain
      administration of LPS activates cytokine production in the brain. In this study,
      we investigated cytokine and neuropeptide mRNA profiles in specific brain regions
      and peripheral organs, as well as serum tumor necrosis factor (TNF)-alpha protein
      levels, in response to the intraperitoneal administration of LPS. For the first
      time, the simultaneous analysis of interleukin (IL)-1beta system components
      (ligand, signaling receptor, receptor accessory proteins, receptor antagonist),
      TNF-alpha, transforming growth factor (TGF)-beta1, glycoprotein 130 (IL-6
      receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, and
      pro-opiomelanocortin (opioid peptide precursor) mRNAs was done in samples from
      specific brain regions in response to peripherally administered LPS. The same
      brain region/organ sample was assayed for all cytokine mRNA components.
      Peripherally administered LPS up-regulated pro-inflammatory cytokine (IL-1beta
      and/or TNF-alpha) mRNAs within the cerebral cortex, cerebellum, hippocampus,
      spleen, liver, and adipose tissue. LPS also increased plasma levels of TNF-alpha
      protein. LPS did not up-regulate inhibitory (anti-inflammatory) cytokine (IL-1
      receptor antagonist and TGF-beta1) mRNAs in most brain regions (except for IL-1
      receptor antagonist in the cerebral cortex and for TGF-beta1 in the hippocampus),
      while they were increased in the liver, and IL-1 receptor antagonist was up
      regulated in the spleen and adipose tissue. Overall, peripherally administered
      LPS modulated the levels of IL-1beta system components within the brain and
      periphery, but did not affect the neuropeptide-related components studied. The
      data suggest specificity of transcriptional changes induced by LPS and that
      cytokine component up-regulation in specific brain regions is relevant to the
      neurological and neuropsychiatric manifestations associated with peripheral LPS
      challenge.

PMID- 11306199
TI  - Quantitative changes in mitochondria of spinal ganglion neurons in aged rabbits.
AB  - Within the context of our research on the age-related structural changes in
      spinal ganglia, we studied the mitochondria of the neuronal perikaryon in the
      spinal ganglia of 12-, 42-, and 79-month-old rabbits. Both the volume of the
      perikaryon and the total mitochondrial mass within the perikaryon increased
      significantly passing from young adult to old animals. Hence, there is no net
      loss of mitochondria in these neurons with age. Since, however, the volume of the
      perikaryon increased by more than 63% while the total mitochondrial mass within
      the perikaryon increased by only 18%, the mean percentage of perikaryal volume
      occupied by mitochondria decreased with age. This decrease is only in very minor
      part a consequence of lipofuscin accumulation, so that the ratio between the
      total mitochondrial mass and the functionally active volume of cytoplasm
      decreased with age. Possible causes of this decrease are discussed briefly.
      Moreover, while the mitochondrial structure did not change, mitochondrial size
      increased with age. Finally, in each of the three age groups both the mean
      percentage volume of mitochondria and the mean mitochondrial size were very
      similar in large light and in small dark neurons.

PMID- 11306200
TI  - Climacteric symptoms in a representative Dutch population sample as measured with
      the Greene Climacteric Scale.
AB  - OBJECTIVE: To measure climacteric symptoms in a population-based survey as
      assessed by the Greene Climacteric Scale and to obtain normative data for the
      total score and subscales (psychological, somatic, vasomotor, and sexual) of the
      Greene Climacteric Scale. METHODS: A sample representative of the Dutch female
      population is interviewed. The sample was drawn from the NIPO-Telepanel (with 269
      women aged 45-65 years) and from the NIPO-CAPI@HOME database (a sample of 235
      women aged 45-65 years). They all filled in the 21 items of the Greene
      Climacteric Scale. The women were divided in four groups according their
      menopausal status: premenopausal, perimenopausal, postmenopausal and
      posthysterectomy. RESULTS: The total score of the Greene Climacteric Scale (mean;
      SD) was in premenopausal women 10.53 +/- 7.36). The score in perimenopausal women
      (15.78 +/- 9.09) and postmenopausal women (15.33 +/- 9.01) were significant
      higher than in the premenopause. The same significant difference between pre and
      peri/postmenopausal women was observed in the psychological, somatic and
      vasomotor subscales. The depression subscale did not change significantly during
      the menopausal transition. Hysterectomized women had the same score as
      postmenopausal women, reflecting the rather high mean age of the hysterectomized
      women (55.8 years). CONCLUSIONS: Prevalence and intensity of climacteric symptoms
      as expressed in the Greene Climacteric Scale do increase during the menopausal
      transition and stay high during the postmenopause. Data presented can be
      considered normative for the Greene Climacteric Scale in a mainly Caucasian
      population.

PMID- 11306201
TI  - Women at mid-life: symptoms, attitudes, and choices, an internet based survey.
AB  - OBJECTIVES: This Internet-based survey questioned middle-aged women (age 35-69)
      regarding their current attitudes, beliefs, symptoms, and treatment choices
      surrounding the climacteric. METHODS: 448 respondents completed the 189 item, WEB
      based survey that included measures of quality of life, lifestyle habits, anxiety
      symptoms, and questions regarding attitude toward and sources of information
      about menopause. RESULTS: Three relationships were hypothesized and supported:
      frequency of self-reported menopause symptoms would be: (1) negatively associated
      with healthy behaviors; (2) positively associated with anxiety; (3) positively
      associated with stress. All measures were self-report. Fatigue, muscle and joint
      aches, and impatience were the most commonly reported symptoms. No particular
      symptom was strongly correlated (r > 0.4) to lifestyle behaviors. Questions
      regarding information exchange reveal that many women are not consulting with
      their healthcare providers about HRT or frequently discussing alternatives. Many
      receive health information from lay sources. CONCLUSIONS: There is a need for
      improved information exchange on this subject. Our results are similar to those
      found using large randomized telephone survey methods, which supports the use of
      the Internet as a reliable and convenient venue for gathering data regarding
      health issues. It is important to consider healthy lifestyle behaviors toward the
      regulation of the climacteric syndrome.

PMID- 11306202
TI  - Effects of hormone replacement therapy on cognitive performance in elderly women.
AB  - OBJECTIVE: To determine the effects of 9 months of hormone replacement therapy
      (HRT) on cognitive performance in women aged 75 years and older. METHODS: A 9
      month randomized, double-blinded, placebo-controlled parallel trial. Fifty-two
      elderly postmenopausal women (age range 75-91 years) without known
      contraindications to HRT or evidence of dementia or depression were enrolled.
      Participants were randomly assigned in a 1:2 ratio to placebo or conjugated
      estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for
      13 days (HRT). Main outcome measures were change from baseline and rate of change
      from baseline for the following psychometric tests: Verbal Fluency Test, Weschler
      Paired Associate Learning and 20 min Delayed Recall, Trailmaking A and B Tests,
      Cancellation Random Letter and Random Form Tests. RESULTS: At baseline, women in
      the HRT group reported a younger age of onset of menopause and a higher
      prevalence of hysterectomy, but otherwise did not differ from women in the
      placebo group. After 9 months of treatment, there were no significant group
      differences for any of the cognitive performance measures. The lack of an
      observed group-by-time difference for all cognitive tests remained after
      controlling for age of onset of menopause, education, and previous hysterectomy.
      CONCLUSIONS: Although conclusions are limited by small sample size and the
      relatively short duration of treatment, results suggest that 9 months of estrogen
      replacement in combination with trimonthly progestin does not improve cognitive
      performance in women over 75 years who do not have dementia or depression.

PMID- 11306203
TI  - Prognosis of breast cancers detected in women receiving hormone replacement
      therapy.
AB  - OBJECTIVE: To determine the influence of hormone replacement therapy (HRT) on
      various prognostic factors of breast cancer (BC). METHODS: A multi-centre case
      control study was conducted, in which a comparison was made of the differences
      between various histological and biological clinical variables of BC detected in
      121 women undergoing HRT at the time of diagnosis, and those cancers detected in
      121 women of similar age not undergoing HRT. The variables were also analysed in
      function of the type of HRT and the length of time treated. RESULTS: The tumours
      detected in patients receiving HRT presented significantly lower tumoural stages,
      a lower degree of affected axillary lymph node dissemination, and a greater
      percentage of well-differentiated tumours and positive estrogen receptors than
      those detected in women not under HRT. Most of these results due principally to
      those patients who were undergoing CONCLUSIONS: Although the better prognosis of
      tumours detected in women receiving HRT may be due largely to their diagnosis at
      earlier stages, there is an increasing body of data leading one to think that
      these tumours present certain histological and biological characteristics that
      make such cancers less aggressive.

PMID- 11306204
TI  - Course of primary headaches during hormone replacement therapy.
AB  - OBJECTIVE: The aim of the present study was to evaluate how hormone replacement
      therapy (HRT) could influence the course of primary headaches in postmenopausal
      women. METHODS: Fifty patients presenting for clinical evaluation of menopausal
      status and suffering from headache were enrolled. The observational period lasted
      7 months during which women filled in a diary with the clinical characteristics
      of headache attacks (frequency, days with headache, severity) and the analgesic
      use (no. of analgesic/month). Climacteric symptoms and both anxiety and
      depression were also measured. At the first visit the patients were divided into
      two groups: those suffering from migraine without aura (MwA) and those suffering
      from episodic tension-type headache (ETTH) and separately randomized. After a
      month of run-in period, they received two different HRT regimen, either: (1)
      transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone
      acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens
      0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up
      evaluations were planned after 1, 3 and 6 months of treatment. RESULTS: While we
      did not observe any significance change regarding headache parameters in ETTH
      patients during both transdermal and oral treatment, the course of migraine was
      significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P
      < 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased
      during HRT in the subgroup assuming oral formulation. On the contrary, no changes
      in the same parameters were found in the group taking transdermal treatment.
      Moreover, while severity of migraine was unaffected by HRT, analgesic consumption
      was significantly increased in the subgroup on oral treatment (F = 6.3; P =
      0.001). CONCLUSIONS: HRT significantly affects the course of headache in
      postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH
      remained stable throughout the observational period, patients suffering from MwA
      worsened their symptoms within the first 3 months of treatment. In particular,
      the oral route of administration significantly worsened migraine in comparison to
      the transdermal route.

PMID- 11306205
TI  - The effects of hormone replacement therapy on lipid peroxidation and antioxidant
      status.
AB  - OBJECTIVE: A number of studies have consistently shown a lower cardiovascular
      risk in women who received postmenopausal hormone replacement therapy (HRT). The
      aim of our study was to examine the effects of HRT on lipid peroxidation and
      antioxidant status, which were likely to be involved in the pathophysiology of
      atherosclerosis. METHODS: We measured erythrocyte and plasma thiobarbituric acid
      reactive substances (TBARS) levels as expression of lipid peroxidation-end
      product malondialdehyde, and also erythrocyte reduced glutathione (GSH) level and
      glutathione peroxidase (GSH-Px) activity as indicators of the antioxidant status
      of the 35 postmenopausal women with HRT (mean age: 51.81 +/- 4.57 yr; body mass
      index (BMI): 26.56 +/- 3.78 kg/m(2)) and 35 postmenopausal women without HRT
      (mean age: 47.50 +/- 3.64; BMI: 27.42 +/-3.43 kg/m2). RESULTS: In the group with
      HRT, erythrocyte and plasma TBARS levels were significantly lower than in the
      group without HRT (P < 0.003 and P < 0.001, respectively). Erythrocyte GSH level
      and GSH-Px activity was found to be increased significantly in the group with HRT
      in comparison with the group without HRT (P < 0.001 and P < 0.001, respectively).
      There was not any correlation between the erythrocyte and plasma TBARS and
      erythrocyte GSH levels and GSH-Px activity with duration of HRT (mean 3.5+/-1.3
      yr). CONCLUSION: Our results show that HRT is beneficial in the protection
      against oxidative damage and can prevent atherosclerotic complications.

PMID- 11306206
TI  - Effects of short-term melatonin administration on lipoprotein metabolism in
      normolipidemic postmenopausal women.
AB  - OBJECTIVE: To investigate the effects of short-term administration of melatonin
      on lipoprotein metabolism in normolipidemic postmenopausal women. METHODS:
      Fifteen such women received 6.0 mg melatonin daily for 2 weeks. Blood was sampled
      before and after treatment. We measured concentrations of total cholesterol and
      total triglyceride in the plasma, as well as the levels of cholesterol,
      triglyceride, and protein in the very low-density lipoprotein (VLDL), low-density
      lipoprotein (LDL), and high-density lipoprotein (HDL). Plasma apolipoprotein
      levels were determined by immunoturbidimetric assay. Activities of lipoprotein
      lipase, hepatic triglyceride lipase, and lecithin cholesterol acyltransferase
      were also determined by enzymatic analysis. RESULTS: Melatonin administration
      significantly increased the plasma levels of triglyceride by 27.2% (P < 0.05), of
      VLDL-cholesterol by 37.2% (P < 0.01), of VLDL-triglyceride by 62.2% (P < 0.001),
      and of VLDL-protein by 30.0% (P < 0.05). However, the plasma total cholesterol
      level and the concentration of lipid and protein in LDL and HDL were not
      significantly affected. Melatonin significantly increased the plasma levels of
      apolipoprotein C-II by 29.5% (P < 0.005), of C-III by 17.1% (P < 0.001), and of E
      by 7.6% (P < 0.05). The plasma levels of apolipoprotein A-I, A-II, and B were not
      altered. Melatonin significantly inhibited the activity of lipoprotein lipase by 
      14.1% (P < 0.05), but did not significantly affect the activities of hepatic
      triglyceride lipase or of lecithin cholesterol acyltransferase. CONCLUSIONS:
      Findings indicate that melatonin increases the plasma level of VLDL particles by
      inhibiting the activity of lipoprotein lipase, but may not affect the plasma
      levels of LDL and HDL particles in postmenopausal women with normolipidemia.

PMID- 11306207
TI  - Detection of testosterone and estrogen receptors in the postmenopausal
      endometrium.
AB  - OBJECTIVE: To detect the presence of testosterone and estrogen receptors in the
      stroma and glandular epithelium in the malignant and non-malignant endometrium.
      METHODS: One hundred and forty-five consecutively-enrolled peri- or
      postmenopausal patients were submitted to diagnostic or operative hysteroscopy.
      These patients either had a history of abnormal uterine bleeding or they were
      asymptomatic with an endometrial echo greater than 4 mm. The presence of estrogen
      and testosterone receptors was determined in endometrial samples by
      immunohistochemistry, using monoclonal antibodies and a streptavidin-biotin
      peroxidase complex system with diamino benzidine as the chromogen. RESULTS:
      Testosterone receptors were detected mainly in the stroma in the non-malignant
      endometrial lesions and in the atypical glandular epithelium in cases of estrogen
      positive endometrial carcinomas. CONCLUSIONS: The presence of testosterone
      receptors in estrogen receptor positive endometrial carcinomas may be involved in
      the mechanism of cell proliferation in these tumors. The strong staining reaction
      for testosterone receptors in the endometrial glands can be considered one of the
      features of invasive malignancy.

PMID- 11306208
TI  - Comparative absorption and variability in absorption of estradiol from a
      transdermal gel and a novel matrix-type transdermal patch.
AB  - OBJECTIVES: To compare the absorption of estradiol from a transdermal gel and a
      novel matrix-type patch and to study the variability in absorption. METHODS:
      Twenty-four healthy postmenopausal women were treated in an open, randomized,
      cross-over study for 18 days with 1.0 mg estradiol daily as a transdermal gel and
      a transdermal patch releasing estradiol 50 microg/24 h without a wash-out between
      the periods. Venous blood samples for estradiol pharmacokinetics were taken on
      the 15th and 18th study days of the gel period and during the 15th-18th study
      days during the patch period. RESULTS: There was no significant difference in
      peak estradiol level or area under the estradiol time-concentration curve between
      the gel and the patch. However, trough estradiol concentration was significantly
      lower and fluctuation higher with the patch. Estradiol time-concentration curves
      on the 15th and 18th study days with the gel were almost superimposable. A
      significant difference was observed in peak estradiol levels, whereas area under
      the curve or trough estradiol level did not differ between the 15th and 18th
      study days with the gel. Inter- and intra-individual coefficients of variability
      were around 30% for peak estradiol level and area under the curve, except for the
      intra-individual coefficient of variability for area under the curve (21%) for
      the gel. The total coefficient of variability for area under the curve was 35%
      for the gel and 39% for the patch. CONCLUSIONS: A daily 1.0 mg estradiol dose as
      a transdermal gel seems to correspond with a matrix-type patch releasing 50
      microg estradiol daily in the extent of estradiol absorption. High variability
      was associated with both treatments, and both the variabilities within and
      between the subjects were high with the gel. Wider than generally applied
      confidence limits should be applied for bioequivalence testing of transdermal
      estradiol formulations.

PMID- 11306209
TI  - 17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or
      20 mg/day) increases bone mineral density in postmenopausal women.
AB  - Although the minimal dose of 17beta-estradiol in hormone replacement regimens was
      originally considered to be 2 mg/day, it is now increasingly accepted that a
      lower dose of 1 mg/day is effective in protecting women from the detrimental
      effects of the menopause. A 1-year, multicentre, double-blind, randomised study
      was conducted in 214 healthy postmenopausal women in order to assess the effect
      of 17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10
      or 20 mg/day) in preventing bone loss. Bone mineral density (BMD) was evaluable
      in 177 women who completed the study. In all women, a statistically significant
      increase from baseline in lumbar vertebrae (L2-L4) BMD was seen after 6 months (
      + 2.4%; p < 0.01); this increase was somewhat greater after 12 months ( + 3.6%; p
      < 0.01). Similar effects were seen in the hip. After 6 months, BMD in the femoral
      neck, Ward's triangle and trochanter had increased by 0.20% (not significant
      [n.s.]), 0.32% (n.s.) and 1.08% (p < 0.01), respectively, compared with baseline.
      Greater increases were again seen after 12 months ( + 1.16%, + 1.62% and + 2.83%,
      respectively), all of which were statistically significant (p < 0.01) compared
      with baseline. The change in BMD from baseline did not differ significantly
      between the three dydrogesterone dosages for either L2-L4 or hip. All dosages
      were well-tolerated and amenorrhoea was achieved in over 70%. In conclusion,
      17beta-estradiol (1 mg/day) continuously combined with dydrogesterone (5, 10 or
      20 mg/day) results in a significant increase in lumbar vertebrae and hip BMD in
      postmenopausal women. The lower dose of oestrogen and the avoidance of cyclical
      bleeding make this a particularly suitable regimen for the prevention and
      treatment of osteoporosis in older women.

PMID- 11306210
TI  - Oral, water-soluble combined estrogen/calcium preparation for postmenopausal
      therapy.
AB  - OBJECTIVES: Estrogen is often prescribed for symptoms and sequelae of ovarian
      estrogen loss after menopause. METHODS: To assess efficacy and acceptability of a
      new, highly soluble estrogen-calcium preparation, we formulated a water-soluble
      powdered combination of estrogen (0.625 mg estrone piperazine sulfate) and
      calcium (1 g, ions) as the highly soluble glycerophosphate salt (Estrosol).
      Effects of once-daily administration on bone mineral turnover of Estrosol
      dissolved in water (n = 11) was compared with 0.625 mg conjugated estrogens
      (Premarin) + 1 g calcium (Tums 500 Calcium Supplement) (n = 8). All women had had
      a previous hysterectomy, were between the ages 40 and 75, within 25% of ideal
      body weight, and had not taken hormonal preparations for at least 3 months.
      Assessment of bone mineral turnover was by monitoring N-telopeptides and bone
      specific alkaline phosphatase (BSAP) on 5 occasions: pretreatment and once during
      each of the 4 months of treatment. RESULTS: Mean N-telopeptide values decreased
      (p = .005) in both groups: Estrosol, 29.2% (40 --> 29 mmol bone collagen
      equivalents (BCE)/mmol creatinine), and Premarin(R) + calcium, 44.8% (33 --> 18
      mmol). Mean BSAP values also decreased (p = 0.007) in both groups: Estrosol,
      12.6% (12.06 --> 10.54 mg/l), Premarin(R) + calcium, 19.1% (11.57 --> 9.36 mg/l).
      The difference between groups for both N-telopeptides and BSAP was not
      significant, although sample size was small. Symptoms (hot flashes, vaginal
      dryness) improved similarly in both groups. Symptoms during treatment (breast or
      nipple tenderness, bloating) also were similar in both groups. Both preparations
      were well-tolerated. There were no changes in CBC, liver function tests,
      electrolytes or urinalyses in either group . CONCLUSIONS: This pilot study
      indicates that the combined, highly water-soluble preparation of estrogen and
      calcium is effective in reducing bone mineral turnover, acceptable and well
      tolerated. Use of this single aqueous preparation may lead to better compliance
      than using two separate pills.

PMID- 11306212
TI  - Duplicative publication of data and other ethical issues in publishing of
      scientific findings.

PMID- 11306213
TI  - Medical care use by treated and untreated substance abusing medicaid patients.
AB  - Medicaid reimbursement costs for county residents at least 18 years old who used
      a treatment service (n = 1043) and residents who were Medicaid enrollees with a
      substance abuse diagnosis but who did not receive treatment (n = 2125) were
      compared. Untreated patients were more likely to be male (47% vs. 39%), white
      (56% vs. 45%), and older (39.7 yrs. +/- 13 SD vs. 35.5 yrs +/- 10 SD). The
      average monthly Medicaid costs ($257) for the untreated were higher in the year
      prior to identification than were costs ($207) for the treated. The monthly costs
      in the six months following identification were $761 for the untreated and $373
      for the treated. The costs in the next six months returned to near the original
      for the treated ($224), while those for the untreated remained higher at $340.
      Medicaid enrollees with untreated substance abuse pose a significant cost to the
      Medicaid system.

PMID- 11306214
TI  - Violent traumatic events and drug abuse severity.
AB  - We examined the occurrence of violent traumatic events, DSM-III-R diagnosis of
      posttraumatic stress disorder (PTSD), and PTSD symptoms, and the relationship of
      these variables to drug abuse severity. One-hundred fifty opioid-dependent drug
      abusers who were participants in a randomized trial of two methadone treatment
      interventions were interviewed using the Diagnostic Interview Schedule, the
      Addiction Severity Index, and the Beck Depression Inventory. Twenty-nine percent
      met diagnostic criteria for PTSD. With the exception of rape, no gender
      differences in the prevalence of violent traumatic events were observed. The
      occurrence of PTSD-related symptoms was associated with greater drug abuse
      severity after controlling for gender, depression, and lifetime diagnosis of
      PTSD. The high rate of PTSD among these methadone patients, the nature of the
      traumatic events to which they are exposed, and subsequent violence-related
      psychiatric sequelae have important implications for identification and treatment
      of PTSD among those seeking drug abuse treatment.

PMID- 11306215
TI  - The Drinking Context Scale. A confirmatory factor analysis.
AB  - The current article examines the development and validation of the Drinking
      Context Scale through the use of confirmatory factor analysis. The scale measures
      the self-reported likelihood of excessive drinking across a number of specific
      social-cognitive drinking contexts. Five-hundred-and-five college students
      adjudicated for breaking university drinking rules filled out the anonymous
      questionnaire. Three factors including convivial, intimate, and negative coping
      contexts were confirmed, and these factors demonstrated good reliability and
      evidence of concurrent validity with other substance abuse indices, including the
      Alcohol Use Disorders Identification Test and the College Alcohol Problem Scale.
      Implications for the DCS as an assessment tool for prevention and early
      intervention with young people are discussed.

PMID- 11306216
TI  - Treatment retention and birth outcomes of crack users enrolled in a substance
      abuse treatment program for pregnant women.
AB  - This study examined characteristics of pregnant crack users that were associated
      with their retention in a residential treatment program and the outcomes of their
      pregnancies. The participant characteristics were assessed when the women were
      admitted to the program, and were related to their demographic status, physical
      health, psychological functioning, substance use, and pregnancy. In general, the
      findings point to the importance of early interventions with this population.
      Implications and limitations of this study, as well as suggestions for future
      research, are discussed.

PMID- 11306217
TI  - An early report on the mother-baby interactive capacity of substance-abusing
      mothers.
AB  - OBJECTIVE: Examination of maternal interactive behavior and psychosocial
      situation of substance-abusing mothers in treatment. METHOD: Twelve mothers with
      an alcohol or drug abuse problem and 12 control mothers were assessed in random
      order with the Parent-Child Early Relational Assessment, for the analysis of
      videotaped mother-infant interactions at 3 and 6 months' postpartum. Depressive
      symptoms were assessed with Edinburgh Postnatal Depression Scale and aspects of
      social support with two Social Support Questionnaires. RESULTS: Substance-abusing
      mothers tended to have more problematic areas in their interactive behavior, a
      tendency which increased during the study period. As was expected, they were more
      often depressive, and experienced more social environment difficulties and less
      social support. CONCLUSIONS: Mothers with alcohol and drug abuse problems need
      intensive professional support in early motherhood, and are seen to be
      particularly motivated to strive for abstinence and accept help at this stage of
      life.

PMID- 11306218
TI  - Treatment compliance in the trajectory of treatment progress among offenders.
AB  - Research on drug treatment process has been limited, with most studies centering
      on individual and program factors associated with successful treatment
      completion. Recent literature has begun highlighting the salience of treatment
      engagement in reducing drug dependence among criminal offenders. This study
      descriptively analyzes incidents of treatment noncompliance identified in monthly
      progress reports for 150 criminal justice-mandated clients in residential
      treatment. We identify seven problem types and seven dimensions of noncompliance
      in the trajectory of treatment engagement. The latter are prevalence, frequency,
      types, specialization, temporal distribution, paths, and correlates. It is found
      that incidents of rule violations are common among criminal justice participants
      of residential treatment. Although for most clients these troubles do not appear
      to evolve into serious obstacles to recovery, a few clients with a high frequency
      of noncompliant behavior never engage in treatment. Clinical implications for
      improving treatment engagement and retention are discussed.

PMID- 11306219
TI  - Treating substance abuse in schizophrenia. An initial report.
AB  - Schizophrenia patients show alarmingly high rates of substance use disorders.
      These patients experience neurocognitive and social deficits that make it
      difficult for them to benefit from effective treatment strategies designed for
      less-impaired populations. Previously, we described Behavioral Treatment for
      Substance Abuse in Schizophrenia and discussed how the program was adapted for
      this population. Here we provide an update of BTSAS, discuss our clinical
      experience running the intervention, and review how it has changed over five
      years of development. We present attendance, participation, and substance use
      data on patients who consented to attend (n = 42), completed (n=14), and dropped
      out (n = 14) of the program. Outcome data are provided for 14 patients, and
      comparisons are made between good (n = 5; > or = 67% of urine tests clean from a
      goal drug over 6 months) and poor (n = 9; < or = 66% of urine tests clean)
      progress patients. Implications for the treatment are discussed.

PMID- 11306220
TI  - Opening the black box. The impact of inpatient treatment services on client
      outcomes.
AB  - This study examined the effects of specific services provided in therapeutic
      communities (TCs) to treatment outcomes. Findings are compared to prior analyses
      of treatment outcomes from the District of Columbia Treatment Initiative (DCI)
      that did not utilize the treatment service information. A subsample of DCI
      clients randomly assigned to two TC programs, who had remained in inpatient
      treatment for at least 60 days, were included in the analyses (n = 371). Logistic
      regression results illustrated that the level of vocational education services
      received was positively associated with completing treatment, and participation
      in group services was associated with decreases in postdischarge arrest. In
      addition, clients who received a greater number of all inpatient services were
      more likely to complete treatment and were less likely to be arrested after
      discharge. Findings suggest that TC programs should consider offering more
      vocational education and group treatment services to enhance prosocial behavior
      following treatment discharge.

PMID- 11306221
TI  - Drug use, HIV-related risk behaviors and dropout status of new admissions and re
      admissions to methadone treatment.
AB  - New entrants to methadone maintenance treatment programs (MMTP) have been
      reported to have different drug use patterns than re-admissions. This study
      assesses differences between 211 re-admissions and 128 new admissions to a NYC
      MMTP. Those new to MMTP were found to be less likely to have ever injected drugs,
      have used more types of drugs, and used heroin at higher frequencies in the 30
      days prior to admission. Within the first three months of treatment, new
      admissions dropped out at a higher rate than the re-admissions (31% vs. 20%, p <
      0.05). The most frequent reasons for dropout, for both groups, included "lost to
      contact" and incarceration. Further research on strategies to address polydrug
      use of MMTP admissions is needed. Efforts to identify concerns of new admissions
      early in treatment, and programs to continue drug treatment services to
      incarcerated clients, are indicated.

PMID- 11306222
TI  - A pilot test of motivational interviewing groups for dually diagnosed inpatients.
AB  - Motivational interviewing is a brief treatment approach designed to produce
      rapid, internally motivated change in addictive behaviors. Motivational
      interviewing shows promise for engaging clients with dual psychiatric and
      psychoactive substance use diagnoses in treatment. While initially developed as
      an individual treatment approach, key motivational enhancement principles may be
      applied to structured group interventions to facilitate its introduction to
      inpatient dual-diagnosis treatment. We describe how we developed and pilot-tested
      a motivational interviewing group for dually diagnosed inpatients, and illustrate
      successes and pitfalls in clinical implementation. Group participants were
      readily engaged by the entertaining format and often provocative content, and
      appeared to benefit from exploration of their ambivalence regarding change.
      Directions for further development and evaluation are proposed.

PMID- 11306223
TI  - The Agency for Healthcare Research and Quality and the U.S. Preventive Services
      Task Force: public support for translating evidence into prevention practice and
      policy.

PMID- 11306224
TI  - Introducing the third US Preventive Services Task Force.

PMID- 11306225
TI  - Evidence-based prevention and international collaboration.

PMID- 11306226
TI  - New USPSTF guidelines: integrating into clinical practice. US Preventive Services
      Task Force.

PMID- 11306227
TI  - The methodologic partnership of effectiveness reviews and cost-effectiveness
      analysis.

PMID- 11306228
TI  - The evolving role of prevention in health care: contributions of the U.S.
      Preventive Services Task Force.

PMID- 11306229
TI  - Current methods of the US Preventive Services Task Force: a review of the
      process.
AB  - The U.S. Preventive Services Task Force (USPSTF/Task Force) represents one of
      several efforts to take a more evidence-based approach to the development of
      clinical practice guidelines. As methods have matured for assembling and
      reviewing evidence and for translating evidence into guidelines, so too have the
      methods of the USPSTF. This paper summarizes the current methods of the third
      USPSTF, supported by the Agency for Healthcare Research and Quality (AHRQ) and
      two of the AHRQ Evidence-based Practice Centers (EPCs). The Task Force limits the
      topics it reviews to those conditions that cause a large burden of suffering to
      society and that also have available a potentially effective preventive service.
      It focuses its reviews on the questions and evidence most critical to making a
      recommendation. It uses analytic frameworks to specify the linkages and key
      questions connecting the preventive service with health outcomes. These linkages,
      together with explicit inclusion criteria, guide the literature searches for
      admissible evidence. Once assembled, admissible evidence is reviewed at three
      strata: (1) the individual study, (2) the body of evidence concerning a single
      linkage in the analytic framework, and (3) the body of evidence concerning the
      entire preventive service. For each stratum, the Task Force uses explicit
      criteria as general guidelines to assign one of three grades of evidence: good,
      fair, or poor. Good or fair quality evidence for the entire preventive service
      must include studies of sufficient design and quality to provide an unbroken
      chain of evidence-supported linkages, generalizable to the general primary care
      population, that connect the preventive service with health outcomes. Poor
      evidence contains a formidable break in the evidence chain such that the
      connection between the preventive service and health outcomes is uncertain. For
      services supported by overall good or fair evidence, the Task Force uses outcomes
      tables to help categorize the magnitude of benefits, harms, and net benefit from
      implementation of the preventive service into one of four categories:
      substantial, moderate, small, or zero/negative. The Task Force uses its
      assessment of the evidence and magnitude of net benefit to make a recommendation,
      coded as a letter: from A (strongly recommended) to D (recommend against). It
      gives an I recommendation in situations in which the evidence is insufficient to
      determine net benefit. The third Task Force and the EPCs will continue to examine
      a variety of methodologic issues and document work group progress in future
      communications.

PMID- 11306230
TI  - The art and science of incorporating cost effectiveness into evidence-based
      recommendations for clinical preventive services.
AB  - As medical technology continues to expand and the cost of using all effective
      clinical services exceeds available resources, decisions about health care
      delivery may increasingly rely on assessing the cost-effectiveness of medical
      services. Cost-effectiveness is particularly relevant for decisions about how to
      implement preventive services, because these decisions typically represent major
      investments in the future health of large populations. As such, decisions
      regarding the implementation of preventive services frequently involve,
      implicitly if not explicitly, consideration of costs. Cost-effectiveness analysis
      summarizes the expected benefits, harms, and costs of alternative strategies to
      improve health and has become an important tool for explicitly incorporating
      economic considerations into clinical decision making. Acknowledging the
      usefulness of this tool, the third U.S. Preventive Services Task Force (USPSTF)
      has initiated a process for systematically reviewing cost-effectiveness analyses
      as an aid in making recommendations about clinical preventive services. In this
      paper, we provide an overview and examples of roles for using cost-effectiveness
      analyses to inform preventive services recommendations, discuss limitations of
      cost-effectiveness data in shaping evidence-based preventive health care
      policies, outline the USPSTF approach to using cost-effectiveness analyses, and
      discuss the methods the USPSTF is developing to assess the quality and results of
      cost-effectiveness studies. While this paper focuses on clinical preventive
      services (i.e., screening, counseling, immunizations, and chemoprevention), the
      framework we have developed should be broadly portable to other health care
      services.

PMID- 11306231
TI  - Screening for skin cancer: recommendations and rationale.

PMID- 11306232
TI  - Screening for skin cancer.
AB  - CONTEXT: Malignant melanoma is often lethal, and its incidence in the United
      States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is
      seldom lethal, but, if advanced, can cause severe disfigurement and morbidity.
      Early detection and treatment of melanoma might reduce mortality, while early
      detection and treatment of nonmelanoma skin cancer might prevent major
      disfigurement and to a lesser extent prevent mortality. Current recommendations
      from professional societies regarding screening for skin cancer vary. OBJECTIVE:
      To examine published data on the effectiveness of routine screening for skin
      cancer by a primary care provider, as part of an assessment for the U.S.
      Preventive Services Task Force. DATA SOURCES: We searched the MEDLINE database
      for papers published between 1994 and June 1999, using search terms for
      screening, physical examination, morbidity, and skin neoplasms. For information
      on accuracy of screening tests, we used the search terms sensitivity and
      specificity. We identified the most important studies from before 1994 from the
      Guide to Clinical Preventive Services, second edition, and from high-quality
      reviews. We used reference lists and expert recommendations to locate additional
      articles. STUDY SELECTION: Two reviewers independently reviewed a subset of 500
      abstracts. Once consistency was established, the remainder were reviewed by one
      reviewer. We included studies if they contained data on yield of screening,
      screening tests, risk factors, risk assessment, effectiveness of early detection,
      or cost effectiveness. DATA EXTRACTION: We abstracted the following descriptive
      information from full-text published studies of screening and recorded it in an
      electronic database: type of screening study, study design, setting, population,
      patient recruitment, screening test description, examiner, advertising targeted
      at high-risk groups or not targeted, reported risk factors of participants, and
      procedure for referrals. We also abstracted the yield of screening data including
      probabilities and numbers of referrals, types of suspected skin cancers,
      biopsies, confirmed skin cancers, and stages and thickness of skin cancers. For
      studies that reported test performance, we recorded the definition of a
      suspicious lesion, the "gold-standard" determination of disease, and the number
      of true positive, false positive, true negative, and false negative test results.
      When possible, positive predictive values, likelihood ratios, sensitivity, and
      specificity were recorded. DATA SYNTHESIS: No randomized or case-control studies
      have been done that demonstrate that routine screening for melanoma by primary
      care providers reduces morbidity or mortality. Basal cell carcinoma and squamous
      cell carcinoma are very common, but detection and treatment in the absence of
      formal screening are almost always curative. No controlled studies have shown
      that formal screening programs will improve this already high cure rate. While
      the efficacy of screening has not been established, the screening procedures
      themselves are noninvasive, and the follow-up test, skin biopsy, has low
      morbidity. Five studies from mass screening programs reported the accuracy of
      skin examination as a screening test. One of these, a prospective study, tracked
      patients with negative results to determine the number of patients with false
      negative results. In this study, the sensitivity of screening for skin cancer was
      94% and specificity was 98%. Several recent case-control studies confirm earlier
      evidence that risk of melanoma rises with the presence of atypical moles and/or
      many common moles. One well-done prospective study demonstrated that risk
      assessment by limited physical exam identified a relatively small (<10%) group of
      primary care patients for more thorough evaluation. CONCLUSIONS: The quality of
      the evidence addressing the accuracy of routine screening by primary care
      providers for early detection of melanoma or nonmelanoma skin cancer ranged from
      poor to fair. We found no studies that assessed the effectiveness of periodic
      skin examination by a clinician in reducing melanoma mortality. Both self
      assessment of risk factors or clinician examination can classify a small
      proportion of patients as at highest risk for melanoma. Skin cancer screening,
      perhaps using a risk-assessment technique to identify high-risk patients who are
      seeing a physician for other reasons, merits additional study as a strategy to
      address the excess burden of disease in older adults.

PMID- 11306233
TI  - Screening for bacterial vaginosis in pregnancy: recommendations and rationale.

PMID- 11306234
TI  - Screening for bacterial vaginosis in pregnancy.
AB  - CONTEXT: Bacterial vaginosis (BV) is a strong independent risk factor for adverse
      pregnancy outcomes. BV is found in 9% to 23% of pregnant women. Symptoms include
      vaginal discharge, pruritus, or malodor, but often women with BV are
      asymptomatic. OBJECTIVES: To determine whether screening and treating pregnant
      women for BV reduces adverse pregnancy outcomes, as part of an assessment for the
      U.S. Preventive Services Task Force. DATA SOURCES: Randomized clinical trials of
      BV treatment in pregnancy that measured pregnancy outcomes were identified from
      multiple searches in MEDLINE from 1966 to 1999, the Cochrane Controlled Trials
      Register and Library, and national experts. STUDY SELECTION: All randomized
      controlled trials of BV treatment in pregnancy that specifically measured
      pregnancy outcomes. DATA EXTRACTION: The following information was abstracted:
      study design and blinding, diagnostic methods, antibiotic interventions, timing
      of antibiotic treatment in pregnancy, criteria for treatment, comorbidities,
      demographic details, risk factors for preterm delivery such as previous preterm
      delivery, compliance, rates of spontaneous and total preterm delivery less than
      37 weeks and less than 34 weeks, preterm premature rupture of membranes, low
      birth weight less than 2500 grams, spontaneous abortion, postpartum endometritis,
      and neonatal sepsis. For each study, we measured the effect of treatment by
      calculating the difference in the rate of a given pregnancy outcome in the
      control group minus the treatment group (the absolute risk reduction [ARR]). A
      stepwise procedure based on the profile likelihood was applied to assess
      heterogeneity, to pool studies when appropriate, and to calculate the mean and
      90% confidence intervals (CIs) for the effect of treatment. DATA SYNTHESIS: Seven
      randomized controlled trials met inclusion criteria for the meta-analysis. We
      found no benefit to BV treatment in average-risk women for any pregnancy outcome.
      Results of studies of high-risk populations, women with previous preterm
      delivery, were statistically heterogeneous. They clustered into two groups; one
      showed no benefit (ARR=-0.08, 90% CI=-0.19 to 0.04), whereas the three
      homogeneous studies showed potential benefit of BV treatment (pooled ARR=0.22;
      90% CI=0.13 to 0.31) for preterm delivery before 37 weeks. Four high-risk studies
      reported results for preterm delivery less than 34 weeks. The pooled estimate
      showed no benefit (ARR=0.04; 90% CI=-0.02 to 0.09), but variation was noted among
      individual studies. Two trials of high-risk women found an increase in preterm
      delivery less than 34 weeks in women who did not have BV but received BV
      treatment. Comparisons of patient populations, treatment regimens, and study
      designs did not explain the heterogeneity among studies. CONCLUSIONS: We found no
      benefit to routine BV screening and treatment. A subgroup of high-risk women may
      benefit from BV screening and treatment; however, there may be a subgroup for
      whom BV treatment could increase the occurrence of preterm delivery.

PMID- 11306235
TI  - Screening adults for lipid disorders: recommendations and rationale.

PMID- 11306236
TI  - Screening and treating adults for lipid disorders.
AB  - CONTEXT: Screening and treatment of lipid disorders in people at high risk for
      future coronary heart disease (CHD) events has gained wide acceptance, especially
      for patients with known CHD, but the proper role in people with low to medium
      risk is controversial. OBJECTIVE: To examine the evidence about the benefits and
      harms of screening and treatment of lipid disorders in adults without known
      cardiovascular disease for the U.S. Preventive Services Task Force. DATA SOURCES:
      We identified English-language articles on drug therapy, diet and exercise
      therapy, and screening for lipid disorders from comprehensive searches of the
      MEDLINE database from 1994 through July 1999. We used published systematic
      reviews, hand searching of relevant articles, the second Guide to Clinical
      Preventive Services, and extensive peer review to identify important older
      articles and to ensure completeness. DATA SYNTHESIS: There is strong, direct
      evidence that drug therapy reduces CHD events, CHD mortality, and possibly total
      mortality in middle-aged men (35 to 65 years) with abnormal lipids and a
      potential risk of CHD events greater than 1% to 2% per year. Indirect evidence
      suggests that drug therapy is also effective in other adults with similar levels
      of risk. The evidence is insufficient about benefits and harms of treating men
      younger than 35 years and women younger than 45 years who have abnormal lipids
      but no other risk factors for heart disease and low risk for CHD events (less
      than 1% per year). Trials of diet therapy for primary prevention have led to long
      term reductions in cholesterol of 3% to 6% but have not demonstrated a reduction
      in CHD events overall. Exercise programs that maintain or reduce body weight can
      produce short-term reductions in total cholesterol of 3% to 6%, but longer-term
      results in unselected populations have found smaller or no effect. To identify
      accurately people with abnormal lipids, at least two measurements of total
      cholesterol and high-density lipoprotein cholesterol are required. The role of
      measuring triglycerides and the optimal screening interval are unclear from the
      available evidence. CONCLUSIONS: On the basis of the effectiveness of treatment,
      the availability of accurate and reliable tests, and the likelihood of
      identifying people with abnormal lipids and increased CHD risk, screening appears
      to be effective in middle-aged and older adults and in young adults with
      additional cardiovascular risk factors.

PMID- 11306237
TI  - Screening for chlamydial infection: recommendations and rationale.

PMID- 11306238
TI  - Screening for chlamydial infection.
AB  - OBJECTIVES: To examine data on the effectiveness of screening for chlamydial
      infection by a physician or other health care professional. Specifically, we
      examine the evidence that early treatment of chlamydial infection improves health
      outcomes, as well as evidence of the effectiveness of screening strategies in
      nonpregnant women, pregnant women, and men, and the accuracy of tests used for
      screening. This review updates the literature since the last recommendation of
      the U.S. Preventive Services Task Force published in 1996. SEARCH STRATEGY: We
      searched the topic of chlamydia in the MEDLINE, HealthSTAR, and Cochrane Library
      databases from January 1994 to July 2000, supplemented by reference lists of
      relevant articles and from experts in the field. Articles published prior to 1994
      and research abstracts were cited if particularly important to the key questions
      or to the interpretation of included articles. SELECTION CRITERIA: A single
      reader reviewed all English abstracts. Articles were selected for full review if
      they were about Chlamydia trachomatis genitourinary infections in nonpregnant
      women, pregnant women, or men and were relevant to key questions in the analytic
      framework. Investigators read the full-text version of the retrieved articles and
      applied additional eligibility criteria. For all topics, we excluded articles if
      they did not provide sufficient information to determine the methods for
      selecting subjects and for analyzing data. DATA COLLECTION AND ANALYSIS: We
      systematically reviewed three types of studies about screening in nonpregnant
      women that relate to three key questions: (1) studies about the effectiveness of
      screening programs in reducing prevalence rates of infection, (2) studies about
      risk factors for chlamydial infection in women, and (3) studies about chlamydial
      screening tests in women. Our search found too few studies on pregnant women to
      systematically review, although pertinent studies are described. We
      systematically reviewed two types of studies about screening in men: (1) studies
      about prevalence rates and risk factors for chlamydial infection in men and (2)
      studies about chlamydial screening tests in men. MAIN RESULTS: Nonpregnant women.
      The results of a randomized controlled trial conducted in a large health
      maintenance organization indicate that screening women selected by a set of risk
      factors reduces the incidence of pelvic inflammatory disease (PID) over a 1-year
      period. Changes in population prevalence rates have not been well documented
      because few studies have employed a representative population sample. Age
      continues to be the best predictor of chlamydial infection in women, with most
      studies evaluating cut-offs at age younger than 25 years. Other risk factors may
      be useful predictors, but these are likely to be population specific. To
      determine the accuracy of screening tests for women, we retrieved and critically
      reviewed 34 articles on test performance. Results indicate that endocervical swab
      specimens and first-void urine specimens have similar performance when using DNA
      amplification tests and have better sensitivity than endocervical culture.
      Recurrent chlamydial infections in women have been associated with increased
      risks for PID and ectopic pregnancies. Pregnant women. The Second Task Force
      recommendations for screening pregnant women were based on two major studies
      demonstrating improved pregnancy outcomes following treatment of chlamydial
      infection. We identified no recent studies on this topic in our literature
      search. Very few studies describe risk factors for chlamydial infection in
      pregnant women. Nonculture testing techniques appear to perform well in pregnant
      women, although studies are limited. Men. No studies described the effectiveness
      of screening or early treatment for men in reducing transmission to women or in
      preventing acute infections or complications in men. Studies of prevalence rates
      and risk factors for chlamydial infection in men are limited. Age lower than 25
      years is the strongest known risk factor cited so far. Results of urethral swab
      specimens compared to first-void urine specimens were similar for DNA
      amplification tests. DNA amplification techniques are more sensitive than
      culture. CONCLUSIONS: Screening women for Chlamydia trachomatis reduces the
      incidence of PID, and it is associated with reductions in prevalence of infection
      in uncontrolled studies. No studies were found to determine whether screening
      asymptomatic men would reduce transmission or prevent acute infections or
      complications. Age is the strongest risk factor for men and women. A variety of
      tests can detect chlamydial infection with acceptable sensitivity and
      specificity, including new DNA amplification tests that use either endocervical
      swabs in women, urethral swabs in men, or first-void urine specimens from men and
      women.

PMID- 11306239
TI  - Natriuretic peptide signalling: molecular and cellular pathways to growth
      regulation.
AB  - The natriuretic peptides (NPs) constitute a family of polypeptide hormones that
      regulate mammalian blood volume and blood pressure. The ability of the NPs to
      modulate cardiac hypertrophy and cell proliferation as well is now beginning to
      be recognized. The NPs interact with three membrane-bound receptors, all of which
      contain a well-characterized extracellular ligand-binding domain. The R1 subclass
      of NP receptors (NPR-A and NPR-B) contains a C-terminal guanylyl cyclase domain
      and is responsible for most of the NPs downstream actions through their ability
      to generate cGMP. The R2 subclass lacks an obvious catalytic domain and functions
      primarily as a clearance receptor. This review focuses on the signal transduction
      pathways initiated by ligand binding and other factors that help to determine
      signalling specificities, including allosteric factors modulating cGMP
      generation, receptor desensitization, the activation and function of cGMP
      dependent protein kinase (PKG), and identification of potential nuclear or
      cytoplasmic targets such as the mitogen-activated protein kinase signalling
      (MAPK) cascade. The inhibition of cardiac growth and hypertrophy may be an
      important but underappreciated action of the NP signalling system.

PMID- 11306240
TI  - Modulation of neutrophil phospholipase C activity and cyclic AMP levels by fMLP
      OMe analogues.
AB  - The N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-OMe (1) analogues for
      Thp-Leu-Ain-OMe (2), for-Thp-Leu-Phe-OMe (3), for-Met-Leu-Ain-OMe (4), for-Met
      Delta(z)Leu-Phe-OMe (5), for-Met-Lys-Phe-For-Met-Lys-Phe (6), for-Met-Leu-Pheol
      COMe (7), and for-Nle-Leu-Phe-OMe (8) have been studied. Some of these have been
      found selective towards the activation of different biological responses of human
      neutrophils. In particular, peptides 2 and 3, which evoke only chemotaxis, are
      ineffective in enhancing inositol phosphate, as well as cyclic AMP (cAMP) levels.
      On the contrary, analogues 5 and 7, which induce superoxide anion production and
      degranulation, but not chemotaxis, significantly increase the levels of the two
      intracellular messengers, as is the case of the full agonists 1 and 6. The Ca(2+)
      ionophore A23187 also activates phospholipase C (PLC) and increases the
      nucleotide levels; when tested in combination with peptide 1 or 5, a supra
      additive enhancement of cAMP concentration is obtained. The PLC blocker, U-73122,
      inhibits the formylpeptide-induced inositol phosphate formation, as well as cAMP
      increase. Moreover, this drug drastically reduces superoxide anion release
      triggered by 1 or 5, whereas it inhibits to a much lesser extent neutrophil
      chemotaxis induced by 1 or 2. Our results suggest that: (i) PLC stimulation is
      involved in cAMP enhancement by formylpeptides; (ii) the activation of PLC by
      formylpeptides, in conditions of increased Ca(2+) influx, induces a supra
      additive enhancement of the nucleotide; (iii) the inability of pure
      chemoattractants to significantly alter the PLC activity or cAMP level,
      differently from full agonists or peptides specific in inducing superoxide anion
      release, appears as a general property. Thus, the activation of neutrophil PLC
      seems essential for superoxide anion release, but less involved in the
      chemotactic response.

PMID- 11306241
TI  - Modulation of CREB and NF-kappaB signal transduction by cannabinol in activated
      thymocytes.
AB  - Cannabinoid compounds inhibit the cAMP signalling cascade in leukocytes. One of
      these compounds, cannabinol (CBN) has been shown to inhibit interleukin-2 (IL-2)
      expression and the activation of cAMP response element binding protein (CREB) and
      nuclear factor for immunoglobulin kappa chain in B cells (NF-kappaB) following
      phorbol-12-myristate-13 acetate (PMA) plus ionomycin (Io) treatment of
      thymocytes. Therefore, the objective of the present studies was to determine the
      role of cAMP and protein kinase A (PKA) in the CBN-mediated inhibition of IL-2,
      CREB, and NF-kappaB in PMA/Io-activated thymocytes. The inhibition of CREB/ATF-1
      phosphorylation, or cAMP response element (CRE) or kappaB DNA binding activity
      produced by CBN in PMA/Io-activated thymocytes, could not be reversed by DBcAMP
      costimulation. Furthermore, DBcAMP failed to reverse the concentration-dependent
      inhibition of IL-2 protein secretion by CBN. Pretreatment of thymocytes with H89
      produced a modest inhibition of PMA/Io-induced CREB/ATF-1 phosphorylation and CRE
      DNA binding activity but H89 had no effect on protein binding to a kappaB motif.
      Additionally, H89 modestly inhibited PMA/Io-induced IL-2 secretion. In light of
      the modest involvement of the cAMP pathway in CBN-mediated inhibition of CREB and
      IL-2 in PMA/Io-activated thymocytes, PD098059 (PD), the MEK inhibitor, was
      utilized to determine the role of ERK MAP kinases in thymocytes. ERKs play a
      critical role in IL-2 production but not for CREB phsophorylation. Collectively,
      these findings suggest that CBN may modulate several signalling pathways in
      activated T cells.

PMID- 11306242
TI  - Specific combinations of G-protein subunits discriminate hormonal signalling in
      rat pituitary (GH(3)) cells in culture.
AB  - It was previously shown that hormone receptor coupling to voltage-dependent
      calcium channels in prolactin and growth hormone-producing GH(3) cells was
      heavily dependent on the specific heterotrimeric combinations of alpha, beta, and
      gamma subunits of the guanosine triphosphate (GTP)-binding protein family.
      Consequently, we assessed whether this was also the case for hormonal modulation
      of the adenylate cyclase (AC) and phospholipase C (PL-C) effector enzymes in
      GH(3) cells in culture. By employing polyclonal antibodies directed towards C
      terminal decapeptides of various alpha subunits in membrane assays, as well as
      antisense oligonucleotides towards certain beta- and gamma-subunit genes in whole
      cell incubations, it was possible to unravel a tentative profile of heterotrimers
      preferred by some of the seven-transmembrane-stretch receptors in their
      modulation of AC and PL-C activities. Vasoactive intestinal peptide (VIP) and
      thyroliberin (TRH) activate membrane-bound AC through alpha(s)beta(2)gamma(2),
      while somatostatin (SRIH) and dopamine (DA) inhibited the AC through
      alpha(i2)beta(1)gamma(3). TRH activated membrane-bound PL-C through
      alpha(q/11)beta(4)gamma(2), while DA inhibition of the PL-C was accomplished via
      alpha(o)beta(3)gamma(4). Hence, it seems that not only the specificity of alpha
      subunits determines the coupling between G protein-associated receptors in GH
      cells, the receptor binding to G proteins also requires certain combinations of
      beta and gamma subunits.

PMID- 11306244
TI  - The mechanism of angiotensin II-induced extracellular signal-regulated kinase-1/2
      activation is independent of angiotensin AT(1A) receptor internalisation.
AB  - The aim of this study was to determine whether internalisation of the angiotensin
      II (Ang II) AT(1A) receptor (AT(1A)R) was a prerequisite for Ang II-induced
      activation of the extracellular signal-regulated kinases, ERK-1/2. The human
      embryonic kidney (HEK293) cell line stably transfected with either the wild-type
      rat AT(1A)R or an internalisation-deficient C-terminal truncated mutant of the
      AT(1A)R (AT(1A)T318R) was used as a model for these studies. Inhibition of
      AT(1A)R internalisation by treatment with an inhibitor of clathrin-mediated
      endocytosis, Concanavalin A (Con A), did not inhibit Ang II-induced ERK-1/2
      activation. Furthermore, cells transfected with the internalisation-deficient
      AT(1A)T318R mutant readily activated ERK-1/2 in response to Ang II. Ang II
      activated ERK-1/2 via two distinct signalling pathways in HEK-AT(1A)R cells.
      Approximately half of Ang II-induced ERK-1/2 activation was protein kinase C
      (PKC)-dependent, and the remainder was calcium- and c-Src-dependent and involved
      transactivation of the epidermal growth factor receptor (EGFR). In summary, Ang
      II-induced activation of ERK-1/2 occurs via two distinct pathways in HEK293
      cells, neither of which requires AT(1A)R internalisation.

PMID- 11306243
TI  - Mechanisms of thrombin-induced MAPK activation associated with cell proliferation
      in human cultured tracheal smooth muscle cells.
AB  - The elevated level of thrombin has been detected in the airway fluids of
      asthmatic patients. However, the implication of thrombin in the pathogenesis of
      bronchial hyperreactivity was not completely understood. Therefore, in this study
      we investigated the effect of thrombin on cell proliferation and p42/p44 mitogen
      activated protein kinase (MAPK) activation in human tracheal smooth muscle cells
      (TSMCs). Thrombin stimulated [3H]thymidine incorporation and p42/p44 MAPK
      phosphorylation in a time- and concentration-dependent manner in TSMCs.
      Pretreatment of TSMCs with pertussis toxin (PTX) significantly inhibited
      [3H]thymidine incorporation and phosphorylation of MAPK induced by thrombin.
      These responses were attenuated by tyrosine kinase inhibitors genistein and
      herbimycin A, phosphatidyl inositide (PI)-phospholipase C (PLC) inhibitor U73122,
      protein kinase C (PKC) inhibitor GF109203X, removal of Ca(2+) by addition of
      BAPTA/AM plus EGTA, and PI 3-kinase inhibitors wortmannin and LY294002. In
      addition, thrombin-induced [3H]-thymidine incorporation and p42/p44 MAPK
      phosphorylation was completely inhibited by PD98059 (an inhibitor of MEK1/2),
      indicating that activation of MEK1/2 was required for these responses.
      Furthermore, overexpression of dominant negative mutants, RasN17 and Raf-301,
      significantly suppressed p42/p44 MAPK activation induced by thrombin and PDGF-BB,
      indicating that Ras and Raf may be required for activation of these kinases.
      These results conclude that the mitogenic effect of thrombin was mediated through
      the activation of Ras/Raf/MEK/MAPK pathway. Thrombin-mediated MAPK activation was
      modulated by PI-PLC, Ca(2+), PKC, tyrosine kinase, and PI 3-kinase associated
      with cell proliferation in cultured human TSMCs.

PMID- 11306245
TI  - Comparison of anti-apoptotic signalling by the insulin receptor and IGF-I
      receptor in preadipocytes and adipocytes.
AB  - We compared the effectiveness of insulin receptor (IR) and type I insulin-like
      growth factor (IGF) receptor (IGFR) cytoplasmic domains in mediating anti
      apoptotic effects in 3T3-L1 preadipocytes and adipocytes. We used TrkC/IR and
      TrkC/IGFR chimeras, stably expressed in these cells and stimulated with
      neurotrophin-3 (NT-3), so as to avoid interference from endogenous receptors.
      After 24-h serum deprivation, 10% of preadipocytes and 2% of adipocytes appeared
      apoptotic as determined by fluorescence-activated cell sorter (FACS) analysis of
      cells stained with propidium iodide (PI) and Annexin V. When NT-3 was added, the
      two chimeras inhibited apoptosis to the same extent by 80% in preadipocytes and
      50% in adipocytes. Mutation of juxtamembrane tyrosines (IR Y960F, IGFR Y950F)
      abrogated these anti-apoptotic effects. Qualitatively similar results were
      obtained by determination of viable rather than apoptotic cells. We conclude that
      IR and IGFR have equal potential to inhibit apoptosis in cell backgrounds, which
      are normally responsive to either IGF-I or insulin.

PMID- 11306246
TI  - Identification of inhibitor binding sites of the cAMP-specific phosphodiesterase
      4.
AB  - Using the technique of site-directed mutagenesis, point mutants of human PDE4A
      have been developed in order to identify amino acids involved in inhibitor
      binding. Relevant amino acids were selected according to a peptidic binding site
      model for PDE4 inhibitors, which suggests interaction with two tryptophan
      residues, one histidine and one tyrosine residue, as well as one Zn(2+) ion.
      Mutations were directed at those tryptophan, histidine, and tyrosine residues,
      which are conserved among the PDE4 subtypes (PDE4A-D) and lie within the high
      affinity 4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram) binding
      domain of human PDE4A (amino acids 276-681 according to the PDE4A sequence
      L20965). Truncations to this region do not alter enzyme activity or inhibitor
      sensitivity. The mutants were expressed in COS1 cells, and the recombinant cyclic
      nucleotide phosphodiesterase (PDE) forms have been characterized in terms of
      their catalytic activity and inhibitor sensitivities. Tyrosine residues 432 and
      602, as well as histidine 588, were found to be involved in inhibitor binding,
      but no interaction was detected between tryptophan and PDE inhibitors tested. To
      test the possibility that other amino acids are of importance for hydrophobic
      interactions, selected phenylalanine residues were also mutated. We found
      phenylalanine 613 and 645 to influence inhibitor binding to PDE4. The significant
      differences in the inhibitor sensitivities of the mutants show that the various
      inhibitors have different enzyme binding sites. Based on the assumption that the
      known side effects of PDE4 inhibitors (like emesis and nausea) are caused
      directly by selective inhibition of different conformation states of PDE4, our
      results may be a hint to differ between PDE4 inhibitors, which have emetic side
      effects (like rolipram), and those that do not have side effects (like N-(3,5
      dichlorpyrid-4-yl)-[1-(4-fluorbenzyl)-5-hydroxy-indol-3-yl]-glyoxylateamide
      [AWD12-281]) by the differences of their binding sites and in that context
      contribute to the development of novel drugs. Furthermore, the identification of
      amino acid interactions proposed by the peptidic binding site model, which was
      used for the mutant selection, verifies the PrGen modeling as a useful method for
      the prediction of inhibitor binding sites in cases where detailed knowledge of
      the protein structure is not available.

PMID- 11306247
TI  - Anatomical MRI study of basal ganglia in bipolar disorder patients.
AB  - This study examined possible anatomical abnormalities in basal ganglia structures
      in bipolar disorder patients. Caudate and putamen gray matter volumes, and globus
      pallidus total volume were measured with magnetic resonance imaging (MRI) in 22
      DSM-IV bipolar patients (age+/-S.D.=36+/-10 years; eight drug-free and 14 lithium
      monotherapy patients) and 22 matched healthy control subjects (age+/-S.D.=38+/-10
      years). No significant differences were found between bipolar patients and
      healthy control subjects for any of the basal ganglia measures (t-tests, P>0.05).
      Age was inversely correlated with left putamen volumes in patients (R=-0.44,
      P=0.04), but not in healthy control subjects (R=-0.33, P=0.14). Older patients
      (>36 years old) had a significantly larger left globus pallidus than younger ones
      (< or =36 years old) (ANOVA, P=0.01). In a multiple regression analysis, after
      entering age as independent variable, the length of illness predicted smaller
      left putamen volumes, explaining 10.4% of the variance (F=4.07, d.f.=2, P=0.03).
      No significant effects of episode type, number of prior episodes, or gender were
      found in any basal ganglia measurements (ANOVA, P>0.05). In conclusion, our
      findings indicate that the basal ganglia may be anatomically preserved in bipolar
      patients. This is in contrast to available findings for unipolar disorder.
      However, our findings also suggest that age and length of illness may have
      significant effects on basal ganglia structures in bipolar patients, which may be
      more pronounced among bipolar I patients, and of relevance for the
      pathophysiology of the disorder.

PMID- 11306248
TI  - Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and.
AB  - The test/retest reproducibility of brain measures of 5-HT2A receptors with
      positron emission tomography (PET) and [18F]deuteroaltanserin was examined in a
      group of eight healthy human subjects. PET measures of 5-HT2A receptors were
      obtained under an equilibrium paradigm, with a 40-min PET acquisition starting
      approximately at 300 min (308+/-11 min) after bolus plus constant infusion of the
      radiotracer. Three brain outcome measures were obtained at equilibrium, V(3)
      (ratio of specific brain uptake to free parent plasma concentration of
      radiotracer), V(3)' (ratio of specific brain uptake to total parent plasma
      concentration) and RT (ratio of specific to non-displaceable brain uptakes).
      V(3)' and RT had high test/retest reproducibility, as measured by mean intra
      subject% change for cortical brain areas of 14.1 and 11.0%, respectively. They
      also had high reliability, as measured by mean intra-class correlation
      coefficients (ICC) for cortical brain areas of 0.86 and 0.88, respectively. V(3)
      had low test/retest reproducibility, due to high variability in the measures of
      free parent tracer in plasma. This study supports the feasibility of equilibrium
      imaging of 5-HT2A receptors with PET and [18F]deuteroaltanserin. The equilibrium
      imaging method with [18F]deuteroaltanserin allows a single acquisition and blood
      measurement to provide an image whose pixel values equal a receptor volume of
      distribution. Since the single image pixel values are proportional to receptor
      densities, the images can be used in pixel-by-pixel statistical methods, such as
      SPM, to assess the distribution and density of 5-HT2A receptors in
      neuropsychiatric disorders.

PMID- 11306249
TI  - Effects of bupropion SR on anterior paralimbic function during waking and REM
      sleep in depression: preliminary findings using.
AB  - This study sought to clarify the effects of bupropion SR on anterior paralimbic
      function in depressed patients by studying changes in the activation of these
      structures from waking to REM sleep both before and after treatment. Twelve
      depressed patients underwent concurrent EEG sleep studies and [18F]fluoro-2-deoxy
      D-glucose ([18F]-FDG) positron emission tomography (PET) scans during waking and
      during their second REM period of sleep before and after treatment with bupropion
      SR. Nine subjects completed pre- and post-treatment waking PET studies. Five
      subjects completed pre- and post-treatment waking and REM sleep PET studies.
      Bupropion SR treatment did not suppress electrophysiologic measures of REM sleep,
      nor did it alter an indirect measure of global metabolism during either waking or
      REM sleep. Bupropion SR treatment reversed the previously observed deficit in
      anterior cingulate, medial prefrontal cortex and right anterior insula activation
      from waking to REM sleep. In secondary analyses, this effect was related to a
      reduction in waking relative metabolism in these structures following treatment
      in the absence of a significant effect on REM sleep relative metabolism. The
      implications of these findings for the relative importance of anterior paralimbic
      function in REM sleep in depression and for the differential effects of anti
      depressant treatment on brain function during waking vs. REM sleep are discussed.

PMID- 11306250
TI  - The measurement of regional cerebral blood flow during the complex cognitive task
      of meditation: a preliminary SPECT study.
AB  - This study measured changes in regional cerebral blood flow (rCBF) during the
      complex cognitive task of meditation using single photon emission computed
      tomography. Eight experienced Tibetan Buddhist meditators were injected at
      baseline with 7 mCi HMPAO and scanned 20 min later for 45 min. The subjects then
      meditated for 1 h at which time they were injected with 25 mCi HMPAO and scanned
      20 min later for 30 min. Values were obtained for regions of interest in major
      brain structures and normalized to whole brain activity. The percentage change
      between meditation and baseline was compared. Correlations between structures
      were also determined. Significantly increased rCBF (P<0.05) was observed in the
      cingulate gyrus, inferior and orbital frontal cortex, dorsolateral prefrontal
      cortex (DLPFC), and thalamus. The change in rCBF in the left DLPFC correlated
      negatively (P<0.05) with that in the left superior parietal lobe. Increased
      frontal rCBF may reflect focused concentration and thalamic increases overall
      increased cortical activity during meditation. The correlation between the DLPFC
      and the superior parietal lobe may reflect an altered sense of space experienced
      during meditation. These results suggest a complex rCBF pattern during the task
      of meditation.

PMID- 11306251
TI  - EEG power, frequency, asymmetry and coherence in male depression.
AB  - Quantitative electroencephalographic (EEG) power topography has served as a
      useful tool for investigating brain regional mechanisms underlying affective
      disorders. In an attempt to examine the role of gender and widen the scope of the
      measurement probes used in these investigations, the traditional power and inter
      hemispheric power ratio indices were supplemented with intra-hemispheric power
      ratios, mean frequency and both inter and intra-hemispheric coherence indices, in
      the comparison of depressed male patients and healthy controls. Resting (eyes
      closed), vigilance controlled EEG recordings from 21 scalp sites were collected
      from 70 male, unmedicated, unipolar major depressive disorder outpatients and 23
      normal control male subjects. Absolute and relative power, frequency, asymmetry
      and coherence measures derived from spectrally analyzed EEGs were subjected to
      univariate analyses for group comparisons as well as to discriminant function
      analysis to examine their utility as classification indices. Compared with
      controls, patients evidenced greater overall relative beta power and, at
      bilateral anterior regions, greater absolute beta power and faster mean total
      spectrum frequency. Inter-hemispheric alpha power asymmetry index differences
      were noted, with controls exhibiting relatively reduced left hemisphere
      activation, and widespread reduced delta, theta, alpha and beta coherence
      indices. Whereas intra-hemispheric theta power asymmetry reduction was exhibited
      in patients bilaterally at all regions, group differences with intra-hemispheric
      beta power asymmetry were unilateral, being restricted to the right hemisphere.
      Discriminant analysis correctly classified 91.3% of the patients and controls.
      Quantitative EEG measurements in male depression appear to describe a pattern of
      aberrant inter-hemispheric synchrony/asymmetry and a profile of frontal
      activation.

PMID- 11306252
TI  - A serial longitudinal quantitative MRI study of cerebral changes in first-episode
      schizophrenia using image segmentation and subvoxel registration.
AB  - Lateral ventricular enlargement is the most consistently replicated brain
      abnormality found in schizophrenia. This article reports a first episode,
      longitudinal study of ventricular volume using high-resolution serial magnetic
      resonance imaging (MRI) and recently developed techniques for image registration
      and quantitation. Baseline and follow-up (on average 8 months later) MRI scans
      were carried out on 24 patients and 12 controls. Accurate subvoxel registration
      was performed and subtraction images were produced to reveal areas of regional
      brain change. Whereas there were no differences between patients and controls
      with respect to the mean change in ventricular volume, the patients were much
      more variable in this respect and showed larger increases and decreases. The
      percentage increase in ventricular size was greater than one standard deviation
      of control values for 14 patients and the percentage decrease exceeded one
      standard deviation in eight patients. Although the finding of progressive
      ventricular enlargement in a proportion of patients supports other studies
      indicating an ongoing neuropathological process in the early stages of
      schizophrenia, the reduction of ventricular size in the remaining patients is
      more difficult to explain. It is suggested that this may reflect improvement in
      nutrition and hydration following treatment.

PMID- 11306253
TI  - SNAREs and the specificity of membrane fusion.
AB  - A major problem of intracellular membrane traffic concerns the way in which
      transport vesicles find and fuse with their target organelles. SNARE proteins are
      involved in fusion, and their mutual recognition could in principle provide the
      necessary specificity. Alternatively, the preliminary tethering of vesicles,
      mediated by peripheral membrane proteins, could hold the key. Previous studies of
      SNARE complex assembly in solution have suggested little specificity, but recent
      experiments with yeast SNAREs anchored in liposomes show that their interactions
      can be highly selective. It is likely that both tethering and SNARE engagement
      contribute to the accuracy of membrane transport.

PMID- 11306254
TI  - Towards an understanding of complex protein networks.
AB  - Large-scale two-hybrid screens have generated a wealth of information describing
      potential protein--protein interactions. When compiled with data from systematic
      localizations of proteins, mutant screens and other functional tests, a network
      of interactions among proteins and between proteins and other components of
      eukaryotic cells can be deduced. These networks can be viewed as maps of the
      cell, depicting potential signaling pathways and interactive complexes. Most
      importantly, they provide potential clues to the function of previously
      uncharacterized proteins. Focusing on recent experiments, we explore these
      protein-interaction studies and the maps derived from such efforts.

PMID- 11306255
TI  - Plexins: making links to the cytoskeleton and reducing the GAPs in our knowledge.

PMID- 11306256
TI  - FRETting about your receptors.

PMID- 11306257
TI  - At long last: identification of an oocyte mitogen receptor.

PMID- 11306263
TI  - Farmer's research goes against the grain.

PMID- 11306264
TI  - Promising clinical trials on kinase inhibitor.

PMID- 11306268
TI  - The Science--Celera deal: incident or trend?

PMID- 11306271
TI  - Ribosome exchange revisited: a mechanism for translation-coupled ribosome
      detachment from the ER membrane.
AB  - In current models, ribosome release from the endoplasmic reticulum (ER) is
      coupled to the termination of protein translation. Thus, coincident with
      termination, membrane-bound ribosomes dissociate into their component subunits
      and are released into the cytosol. Here, we review past and current data and
      propose that the affinity of the ribosome for the ER membrane is decreased during
      translation, with ribosome release occurring when a membrane-bound ribosome is
      engaged in the synthesis of a protein lacking a signal sequence. Our model
      emphasizes a role for the conformation of the large ribosomal subunit in the
      regulation of membrane affinity and provides a mechanism for translation-coupled
      ribosome release.

PMID- 11306272
TI  - Secretory granule biogenesis: rafting to the SNARE.
AB  - Regulated secretion of hormones occurs when a cell receives an external stimulus,
      triggering the secretory granules to undergo fusion with the plasma membrane and
      release their content into the extracellular milieu. The formation of a mature
      secretory granule (MSG) involves a series of discrete and unique events such as
      protein sorting, formation of immature secretory granules (ISGs), prohormone
      processing and vesicle fusion. Regulated secretory proteins (RSPs), the proteins
      stored and secreted from MSGs, contain signals or domains to direct them into the
      regulated secretory pathway. Recent data on the role of specific domains in RSPs
      involved in sorting and aggregation suggest that the cell-type-specific
      composition of RSPs in the trans-Golgi network (TGN) has an important role in
      determining how the RSPs get into ISGs. The realization that lipid rafts are
      implicated in sorting RSPs in the TGN and the identification of SNARE molecules
      represent further major advances in our understanding of how MSGs are formed. At
      the heart of these findings is the elucidation of molecular mechanisms driving
      protein--lipid and protein--protein interactions specific for secretory granule
      biogenesis.

PMID- 11306273
TI  - The ins and outs of calreticulin: from the ER lumen to the extracellular space.
AB  - Calreticulin was first isolated 26 years ago. Since its discovery as a minor
      Ca(2+)-binding protein of the sarcoplasmic reticulum, the appreciation of its
      importance has grown, and it is now recognized to be a multifunctional protein,
      most abundant in the endoplasmic reticulum (ER). The protein has well-recognized
      physiological roles in the ER as a molecular chaperone and Ca(2+)-signalling
      molecule. However, it has also been found in other membrane-bound organelles, at
      the cell surface and in the extracellular environment, where it has recently been
      shown to exert a number of physiological and pathological effects. Here, we will
      focus on these less-well-characterized functions of calreticulin.

PMID- 11306274
TI  - Integrin-associated protein (CD47) and its ligands.
AB  - Integrin-associated protein (IAP or CD47) is a receptor for thrombospondin family
      members, a ligand for the transmembrane signaling protein SIRP alpha and a
      component of a supramolecular complex containing specific integrins,
      heterotrimeric G proteins and cholesterol. Peptides containing a VVM motif in the
      C-terminal domain of thrombospondins are agonists for CD47, initiating
      heterotrimeric Gi protein signaling that augments the functions of integrins of
      the beta 1, beta 2 and beta 3 families, thus modulating a range of cell
      activities including platelet activation, cell motility and adhesion, and
      leukocyte adhesion, migration and phagocytosis.

PMID- 11306275
TI  - Congenital disorders of glycosylation: genetic model systems lead the way.
AB  - N-linked glycosylation is the most frequent modification of secretory proteins in
      eukaryotic cells. The highly conserved glycosylation process is initiated in the
      endoplasmic reticulum (ER), where the Glc(3)Man(9)GlcNAc(2) oligosaccharide is
      assembled on the lipid carrier dolichylpyrophosphate and then transferred to
      selected asparagine residues of polypeptide chains. In recent years, several
      inherited human diseases, congenital disorders of glycosylation (CDG), have been
      associated with deficiencies in this pathway. The ER-associated glycosylation
      pathway has been studied in the budding yeast Saccharomyces cerevisiae, and this
      model system has been invaluable in elucidating the molecular basis of novel
      types of CDG.

PMID- 11306276
TI  - Paracrine regulation of keratinocyte proliferation and differentiation.
AB  - The histoarchitecture and function of the epidermis depend on a well-controlled
      balance between keratinocyte proliferation and differentiation. This balance is
      perturbed after skin injury, and imbalance is a characteristic feature of major
      human skin diseases such as psoriasis and epidermal cancers. Recent studies have
      highlighted the importance of fibroblast-derived soluble factors for the
      regulation of keratinocyte proliferation and differentiation. Therefore,
      identification of these paracrine-acting factors and the elucidation of their
      mechanisms of action are necessary for understanding epidermal homeostasis,
      repair and disease, and these approaches will offer new potential targets for
      drug therapy. Here, we review exciting recent findings on the identification,
      regulation and function of paracrine-acting cytokines in the skin. In particular,
      we describe the role of fibroblast-derived mitogens as regulators of keratinocyte
      proliferation and differentiation, and we summarize the regulation of these
      factors by keratinocyte-derived interleukin 1 that involves the transcription
      factors c-Jun and JunB.

PMID- 11306277
TI  - Pictures in cell biology. Spatial dynamics of rRNAs.

PMID- 11306278
TI  - Stay tuned for some importin news about spindle assembly.

PMID- 11306279
TI  - Vacuoles fuse with V0.

PMID- 11306280
TI  - Where the nucleus comes from.

PMID- 11306281
TI  - AP-3: what color's your coat?

PMID- 11306282
TI  - Phagocytosis in C. elegans: CED-1 reveals its secrets.

PMID- 11306294
TI  - LIS1: cellular function of a disease-causing gene.
AB  - Brain development is severely defective in children with lissencephaly. The
      highly organized distribution of neurons within the cerebral cortex is disrupted,
      a condition that might arise from improper migration of neuronal progenitors to
      their cortical destinations. Type I lissencephaly results from mutations in the
      LIS1 gene, which has been implicated in the cytoplasmic dynein and platelet
      activating factor pathways. Recent studies have identified roles for the product
      of LIS1 in nuclear migration, mitotic spindle orientation and chromosome
      alignment, where it appears to act in concert with cytoplasmic dynein. A unifying
      hypothesis for the subcellular function of LIS1 is presented.

PMID- 11306295
TI  - Control of spindle polarity and orientation in Saccharomyces cerevisiae.
AB  - Control of mitotic spindle orientation represents a major strategy for the
      generation of cell diversity during development of metazoans. Studies in the
      budding yeast Saccharomyces cerevisiae have contributed towards our present
      understanding of the general principles underlying the regulation of spindle
      positioning in an asymmetrically dividing cell. In S. cerevisiae, the mitotic
      spindle must orient along the cell polarity axis, defined by the site of bud
      emergence, to ensure correct nuclear division between the mother and daughter
      cells. Establishment of spindle polarity dictates this process and relies on the
      concerted control of spindle pole function and a precise program of cues
      originating from the cell cortex that directs cytoplasmic microtubule attachments
      during spindle morphogenesis. These cues cross talk with the machinery
      responsible for bud-site selection, indicating that orientation of the spindle in
      yeast cells is mechanistically coupled to the definition of a polarity axis and
      the division plane. Here, we propose a model integrating the inherently
      asymmetric properties of the spindle pathway with the program of positional
      information contributing towards orienting the spindle in budding yeast. Because
      the basic machinery orienting the spindle in higher-eukaryotic cells appears to
      be conserved, it might be expected that similar principles govern centrosome
      asymmetry in the course of metazoan development.

PMID- 11306297
TI  - Magic bullets for protein kinases.
AB  - A chemical-genetic method for the generation of target-specific protein kinase
      inhibitors has been developed recently. This strategy utilizes a functionally
      silent active-site mutation to sensitize a target kinase to inhibition by a small
      molecule that does not inhibit wild-type kinases. Tyrosine and serine/threonine
      kinases are equally amenable to the drug-sensitization approach, which has been
      used to generate selective inhibitors of mutant Src-family kinases, Abl-family
      kinases, cyclin-dependent kinases, mitogen-activated kinases, p21-activated
      kinases and Ca(2+)/calmodulin-dependent kinases. The designed inhibitors are
      specific for the sensitized kinase in a cellular background where the wild-type
      kinase has been inactivated. By these means, kinase-sensitization has been used
      systematically to generate and analyze conditional alleles of several yeast
      protein kinases in vivo.

PMID- 11306298
TI  - Moving the insulin-regulated glucose transporter GLUT4 into and out of storage.
AB  - The glucose transporter isoform GLUT4 is unique among the glucose transporter
      family of proteins in that, in resting cells, it is sequestered very efficiently
      in a storage compartment. In insulin-sensitive cells, such as fat and muscle,
      insulin stimulation leads to release of GLUT4 from this reservoir and its
      translocation to the plasma membrane. This process is crucial for the control of
      blood and tissue glucose levels. Investigations of the composition and structure
      of the GLUT4 storage compartment, together with the targeting motifs that direct
      GLUT4 to this compartment, have been extensive but have been controversial.
      Recent findings have now provided a clearer consensus of opinion on the
      mechanisms involved in the formation of this storage compartment. However,
      another controversy has now emerged, which is unresolved. This concerns the issue
      of whether the insulin-regulated step occurs at the level of release of GLUT4
      from the storage compartment or at the level at which released vesicles fuse with
      the plasma membrane.

PMID- 11306299
TI  - Peter Satir -- investigating the structural basis for cell function.
AB  - Peter Satir has devoted his research career to elucidating the structural basis
      for ciliary motility. His ingenious use of structural analysis, combined with
      identification of powerful model systems, provided a model for the sliding
      microtubule hypothesis of ciliary bending and led to the discovery that dynein is
      a 'minus-end'-directed motor whose regulated activity underpins the bending
      motion of cilia. Here, we focus on ciliary motility to illustrate Satir's
      pioneering contributions to cell biology.

PMID- 11306300
TI  - Airway complications after lung transplantation: a review of 151 anastomoses.
AB  - OBJECTIVE: To analyze the incidence, treatment and follow up of airway
      complications after lung transplantation. METHODS: From October 1993 to April
      2000, 104 lung transplants were performed in 101 patients. One hundred and fifty
      one bronchial anastomoses at risk were included in the study (29 single lung and
      61 sequential double lung). Donor lungs were flushed both antegradely and
      retrogradely with Eurocollins. In the recipients, either a single or a sequential
      bilateral lung transplantation was performed when indicated. The bronchial
      anastomosis was telescoped and covered with peribronchial tissue in all cases.
      Postoperative fiberoptic bronchoscopic examinations were dictated by clinical
      grounds. Recipient variables were recorded and analyzed to assess possible
      differences between both complicated and non-complicated groups. RESULTS: Eight
      bronchial anastomotic complications (5.3%) occurred in six patients (6.8%). All
      complicated cases developed in sequential bilateral lung recipients (P=0.08):
      stenosis (n=5), granulation tissue (n=2), and bronchial dehiscence (n=1).
      Treatment consisted of lobectomy and subsequent completion pneumonectomy in one
      patient, rigid bronchoscopy dilation in two, balloon bronchodilation in two,
      laser debridement and stenting in one, and conservative therapy in two cases. One
      patient with severe sepsis and bronchial dehiscence died on day +30. The rest of
      the patients remain well so far. Airway complications were related to longer
      intubation periods (P<0.01). Other perioperative donor and recipient factors
      including the incidence of infections and acute rejection episodes, and actuarial
      survival, did not differ between groups. CONCLUSION: In our experience, the
      incidence of airway complications after lung transplantation is 5.3%. The careful
      surgical technique and organ preservation, the close surveillance of rejection
      and infection, and early postoperative extubation might play a role in reducing
      this incidence. Either surgical therapy or bronchoscopic dilation and stenting
      methods may contribute to resolve these complications.

PMID- 11306301
TI  - Pulmonary sequestration: a comparison between pediatric and adult patients.
AB  - OBJECTIVE: Modern large single institutional reports on pulmonary sequestration
      (PS) are extremely rare. We were interested in comparing patients with PS
      referred by our pediatric versus adult pulmonologists. METHODS: Hospital notes of
      all patients operated on between 1978 and 1997 for a congenital broncho-pulmonary
      malformation were reviewed. In 28 patients, the parenchymal lesion was
      vascularized by a systemic artery and was separated from the bronchial tree, thus
      matching the strict definition of PS. Patient characteristics and outcome were
      analyzed comparing the pediatric group (< or =16 years: n=13; mean age, 3+/-5
      years) versus the adult group (>16 years: n=15; mean age, 33+/-13 years).
      RESULTS: No significant differences between both groups were observed in sex,
      side, type of sequestration, pulmonary venous drainage, associated anomalies,
      hospital and late outcome, and patient's overall score. Patients (n=21) with the
      intralobar type of sequestration presented significantly more often with an
      infection when compared with patients (n=7) with the extralobar type (91 versus
      14%; P=0.0033). When compared with the pediatric group, patients in the adult
      group had significantly more respiratory infections (87 versus 38%; P=0.016), and
      also required a lobectomy more often (67 versus 31%; P=0.056). CONCLUSIONS: The
      extralobar type of sequestration often remains asymptomatic, and is usually an
      incidental finding during infancy. The intralobar type mostly presents with
      recurrent infections in adulthood resulting in more lobectomies. We believe these
      findings support our current policy to remove any pulmonary malformation whenever
      diagnosed in order to: (1), prevent infection and other potentially serious late
      complications which may compromise the surgical outcome; and (2), enhance the
      chance of a parenchymal-sparing resection.

PMID- 11306302
TI  - Recurrences following videothoracoscopic treatment of primary spontaneous
      pneumothorax: the role of redo-videothoracoscopy.
AB  - OBJECTIVE: There is very little experience regarding recurrences following
      videothoracoscopic (VATS) treatment of primary spontaneous pneumothorax. We
      report our experience with 19 patients who underwent redo-VATS to evaluate the
      feasibility of such surgical approach. METHODS: From July 1, 1992 to September 1,
      2000, out of 2136 VATS procedures performed at our institution, 597 patients
      (27.94%) underwent VATS treatment of primary spontaneous pneumothorax with a
      recurrence rate of 3.85% (23 cases). Primary VATS treatment in these patients
      was: talc poudrage, three cases; subtotal pleurectomy, three cases; ligation of
      the bullae + subtotal pleurectomy, 12 cases; stapling of the bullae + subtotal
      pleurectomy, two cases; ligation of the bullae + talc poudrage, one case;
      stapling of the bullae + talc poudrage, one case. Treatment of the 23 recurrences
      included: 15 redo-VATS, four standard thoracotomy, three pleural drainage, one
      bed rest. Four additional redo-VATS were also performed in four patients operated
      on in different institutions. Redo-VATS showed residual bullae in nine cases and
      a minimal leaking area in one patient; in the remaining nine patients no lesion
      was found. Redo-VATS treatment was: stapling of the bullae + talc poudrage in
      nine patients; suture of the leaking area with a no-knife stapler + talc poudrage
      in one patient; isolated talc poudrage in the remaining nine patients with no
      evidence of bullae or blebs. RESULTS: No mortality was reported; no major
      complications occurred. The conversion rate in the group of redo-VATS was 5.2%
      (one patient). At a mean follow-up of 32 months no patient showed recurrent
      pneumothorax. CONCLUSIONS: In the light of our initial experience, redo-VATS
      seems to be a promising tool for the surgical therapy of recurrences following
      VATS treatment of primary spontaneous pneumothorax.

PMID- 11306303
TI  - Esophageal reconstruction for hypopharyngoesophageal strictures after corrosive
      injury.
AB  - OBJECTIVE: To evaluate the surgical outcome of patients with caustic stricture of
      the hypopharyngoesophagus. MATERIALS AND METHODS: During a 25-year period, we
      performed esophageal reconstruction in 152 patients with diffuse or multiple
      caustic esophageal stricture. Of them, esophageal substitute was pulled up and
      anastomosed to the hypopharynx in 50 (33%) patients, and anastomosed to the
      cervical esophagus in the other 102 (67%) patients. Patients whose esophageal
      substitute anastomosed to the hypopharynx were enrolled to the present study.
      Among these 50 study patients, 13 underwent ablation of damaged organs and
      feeding jejunostomy in acute stage of corrosive injury, and the remaining 37
      patients were initially organ preserved with or without feeding gastrostomy or
      jejunostomy. Six patients had respiratory distress caused by laryngotracheal
      stricture. The ileocolon (28/50) was commonly used as an esophageal substitute in
      reconstruction and most substitutes (43/50) went through the substernal route.
      RESULTS: There was one operative death. Eight (16%) patients had major early
      postoperative complications. Six patients underwent revision for late stenosis of
      hypopharyngeal anastomosis, and one redoing reconstruction using the jejunum
      because of failure of the transplanted ileocolon. Postoperatively, swallow
      function and maintaining body weight were considered good in 42 patients (84%)
      after an average of 8 months follow-up. Five of six patients who underwent
      concomitant tracheostomy or laryngosurgery for laryngotracheal stricture got
      unsatisfactory result. The surgical outcome of the study patients was worse than
      that in patients with esophageal substitute anastomosed to a healthy cervical
      esophagus. In the later group of patients, 95/102 (93%) had good swallow function
      and only 7/102 (6.8%) had major early complications. CONCLUSION: Caustic
      stricture of the hypopharyngoesophagus is a challenging reconstructive problem. A
      successful reconstruction requires a correct hypopharyngeal opening and
      anastomosis, a good esophageal substitute, and a patent esophageal route and
      airway.

PMID- 11306304
TI  - Functional results following pharyngolaryngooesophagectomy with free jejunal
      graft reconstruction.
AB  - OBJECTIVE: A free jejunal graft is used for reconstruction following
      pharyngolaryngooesophagectomy, due to the relative ease of harvesting, low donor
      site morbidity and a lumen diameter compatible with that of the oesophagus. Our
      aim is to evaluate the postoperative outcome and functional results of the
      procedure. METHODS: Retrospective analysis of 20 consecutive patients, with a
      mean age of 62.5 years (range 48--76), who underwent free jejunal reconstruction
      following pharyngolaryngooesophagectomy for laryngeal malignancy. Surgery was
      performed secondary to radiotherapy or as the main stem of treatment. The
      functional results were assessed at 6 months and 1 year and correlated with
      postoperative morbidity. Chi-square test was used for statistical significance
      and Kaplan--Meyer to estimate survival. RESULTS: There were six transient leaks
      and six cases with anastomotic stricture. There was no morbidity associated with
      the donor site and the perioperative mortality (30 days) was zero. At 6 months,
      13 (87%) out of the 15 patients alive had satisfactory speech and 11 (78%) had
      satisfactory swallowing. At 1 year, 11 patients were alive and maintained a
      satisfactory speech, while nine (81%) of them were eating well. The incidence of
      leaks, strictures, or the moment of radiotherapy has no influence on the
      functional outcome. The 1- and 3-year survival rates were 52.3 and 33.2%,
      respectively. CONCLUSIONS: A free jejunal graft reconstruction is technically
      demanding, but provides a near-physiologic swallowing mechanism, avoiding the
      complications of a gastric pull-up procedure. Functional results are good and
      justify the procedure despite the relatively high co-morbidity.

PMID- 11306305
TI  - Active cooling during open repair of thoraco-abdominal aortic aneurysms improves
      outcome.
AB  - OBJECTIVE: Evaluate impact of active cooling with partial cardiopulmonary bypass
      (CPB) and low systemic heparinization during open repair of thoracoabdoninal
      aortic aneurysms. METHODS: Prospective analysis of 100 consecutive patients
      undergoing surgical repair of thoracoabdominal aortic aneurysms. Partial CPB and
      normothermic (36 degrees C) or hypothermic (29 degrees C) perfusion was selected
      in accordance to the surgeons preference. In the hypothermic group, aortic cross
      clamp was applied when the target temperature of the venous blood was achieved
      and rewarming was started after declamping. RESULTS: 52/100 patients (62.2+/-10.9
      years) received normothermic and 48/100 patients hypothermic perfusion (63.8+/
      10.6 years: NS). Emergent procedures accounted for 18/52 (35%) with normothermia
      vs. 21/48 (44%: NS) with hypothermia. The number of aortic segments (eight =
      maximum including arch and bifurcation) replaced was 3.9+/-1.5 with normothermia
      vs. 4.1+/-1.5 with hypothermia (NS); Crawford type II aneurysms accounted for
      21/52 patients (40%) for normothermia vs. 20/48 (42%:NS) for hypothermia. Total
      clamp time was 38+/-21 min with normothermia vs. 47+/-28 min with hypothermia
      (P=0.05). Pump time was 55+/-28 min with normothermia vs. 84+/-34 min with
      hypothermia (P=0.001). Mortality at 30 days was 8/52 patients (15%) with
      normothermia vs. 2/48 (4%) with hypothermia (P=0.06; odds ratio = 4.1).
      Parapareses/plegias occurred in 4/52 patients (8%) with normothermia vs. 4/48
      (8%) with hypothermia (NS). Revisions for bleeding were required in 4/52 patients
      (8%) with normothermia vs. 2/48 patients (4%) with hypothermia (P=0.38).
      Revisions for distal vascular problems were necessary in 5/52 patients (10%) with
      normothermia vs. 2/48 (4%) with hypothermia (P=0.25). Freedom from death,
      paraplegia, and surgical revision was 89.9% with normothermia vs. 94.8% with
      hypothermia (P=0.04; odds ratio 2.0). CONCLUSIONS: Active cooling during repair
      of thoracoabdominal aortic aneurysms allows for longer cross-clamp times, more
      complex repairs and improves outcome.

PMID- 11306306
TI  - Is aortic surgery using hypothermic circulatory arrest in octogenarians
      justifiable?
AB  - OBJECTIVE: This study was undertaken to analyze the risk of mortality and
      neurological complications after aortic surgery requiring hypothermic circulatory
      arrest (HCA) in octogenarians. METHODS: All patients of >80 years at the time of
      aortic surgery requiring HCA since 1988 were examined. Of 51 patients, 23 were
      male; the median age was 83. Twenty-six (51%) had proximal repair; the arch was
      replaced in eight (16%), and 17 (33%) had descending aorta repair. Eleven (22%)
      were emergencies. Multivariate analysis was carried out to determine the risk
      factors for in-hospital mortality and/or stroke (adverse outcome) using variables
      with P<0.1 after univariate analysis. RESULTS: The hospital mortality was 16%.
      Five patients suffered strokes (9.8%): only one survived >6 months, and three
      died before discharge. The overall adverse outcome was 22%, but elective
      operation was associated with much better results, with an adverse outcome of
      only 3.6% after operations via a median sternotomy. Adverse outcome was
      strikingly higher with more distal resections via a left thoracotomy: 47 vs. 8.8%
      for ascending aorta/arch resections (P=0.003). Emergency operation via a lateral
      thoracotomy was associated with a prohibitively high adverse outcome. Twenty-nine
      patients (73%) had temporary neurological dysfunction (TND). Multivariate
      analysis revealed emergency operation (P=0.01; odds ratio (OR), 10.6) and
      operations via a lateral thoracotomy (P=0.008; OR, 11) as independent
      preoperative predictors of adverse outcome. The overall survival was 66% at 2
      years and 39% at 5 years, compared with 85 and 52% among age- and sex-matched
      controls. CONCLUSIONS: Aortic surgery utilizing HCA in octogenarians can be
      performed with an acceptable risk of mortality and stroke. From the evidence in
      this study, it seems that elective aneurysm repair via a median sternotomy can be
      undertaken for the usual indications, even in octogenarians. However, the
      enhanced vulnerability of the brain in the elderly is reflected by a high early
      mortality following stroke, and a high incidence of TND. Emergency operations
      increase the possibility of adverse outcome dramatically, and patients who
      require a lateral thoracotomy are at significantly higher risk than those
      operated via a median sternotomy.

PMID- 11306307
TI  - Fibrin gel -- advantages of a new scaffold in cardiovascular tissue engineering.
AB  - OBJECTIVE: The field of tissue engineering deals with the creation of tissue
      structures based on patient cells. The scaffold plays a central role in the
      creation of 3-D structures in cardiovascular tissue engineering like small
      vessels or heart valve prosthesis. An ideal scaffold should have tissue-like
      mechanical properties and a complete immunologic integrity. As an alternative
      scaffold the use of fibrin gel was investigated. METHODS: Preliminary, the
      degradation of the fibrin gel was controlled by the supplementation of aprotinin
      to the culture medium. To prevent tissue from shrinking a mechanical fixation of
      the gel with 3-D microstructure culture plates and a chemical fixation with poly
      L-lysine in different fixation techniques were studied. The thickness of the gel
      layer was changed from 1 to 3 mm. The tissue development was analysed by light,
      transmission and scanning electron microscopy. Collagen production was detected
      by the measurement of hydroxyproline. Injection molding techniques were designed
      for the formation of complex 3-D tissue structures. RESULTS: The best tissue
      development was observed at an aprotinin concentration of 20 microg per cc
      culture medium. The chemical border fixation of the gel by poly-L-lysine showed
      the best tissue development. Up to a thickness of 3 mm no nutrition problems were
      observed in the light and transmission electron microscopy. The molding of a
      simplified valve conduit was possible by the newly developed molding technique.
      CONCLUSION: Fibrin gel combines a number of important properties of an ideal
      scaffold. It can be produced as a complete autologous scaffold. It is moldable
      and degradation is controllable by the use of aprotinin.

PMID- 11306308
TI  - Edge-to-edge mitral repair: gradients and three-dimensional annular dynamics in
      vivo during inotropic stimulation.
AB  - OBJECTIVE: The edge-to-edge (Alfieri) mitral repair technique appears to be
      clinically promising, but the potential for functional mitral stenosis,
      especially with exercise, remains a concern. We used the myocardial marker method
      combined with Doppler echocardiography to evaluate mitral annular (MA) three
      dimensional (3-D) dynamics and transvalvular gradients after leaflet
      approximation before and during dobutamine infusion. METHODS: Eight adult sheep
      underwent implantation of eight myocardial markers around the MA and nine in the
      left ventricle. Mitral leaflet edges were approximated at the valve center and
      micromanometers were placed in the left ventricle and atrium. The animals were
      studied with biplane videofluoroscopy to determine 3-D marker coordinates for
      computation of precise 3-D MA area and left ventricular (LV) volume. Epicardial
      Doppler echocardiography measured peak and mean diastolic mitral valve gradients
      at baseline and during dobutamine infusion (10 microg/kg per min). RESULTS:
      During dobutamine stimulation, left ventricular dP/dt increased from 1776+/-712
      to 3390+/-618 mmHg/s (P=0.002), and cardiac output (CO) increased from 2.7+/-1.1
      to 5.1+/-1.2 l/min (P=0.009). Mitral annular area (MAA) at end-diastole (ED) fell
      from 8.6+/-1.4 to 7.0+/-1.8 cm(2) (P=0.001) with inotropic stimulation, but only
      a modest increase was observed in mean (1.4+/-0.4 vs. 2.4+/-1.0 mmHg, P=0.046)
      and peak (2.7+/-0.8 vs. 4.9+/-2.5 mmHg, P=0.03) diastolic mitral valve gradients.
      MAA changed dynamically throughout the cardiac cycle, reflecting normal
      physiology, but the magnitude of MAA change was augmented during inotropic
      stimulation (18+/-5% and 27+/-4% for control and dobutamine, respectively;
      P=0.004). CONCLUSION: Dobutamine increased CO by 89% and decreased ED annular
      area by 19% after edge-to-edge repair, yet only a small increase in valve
      gradient occurred. Marker analysis showed enhanced dynamic motion of the mitral
      annulus. Thus, the edge-to-edge mitral valve repair was not associated with
      substantial transvalvular obstruction during high flow conditions and did not
      perturb normal MA 3-D dynamics in normal ovine hearts.

PMID- 11306309
TI  - The efficacy of the Cox/maze procedure combined with mitral valve surgery: a
      matched control study.
AB  - OBJECTIVE: To evaluate the results of the maze procedure combined with mitral
      valve (MV) surgery in patients with chronic atrial fibrillation (AF). METHODS:
      From 1994--1999, 47 patients with chronic AF underwent the maze procedure
      combined with MV surgery (maze group). They were compared to 47 patients matched
      for age, sex, left ventricular function and type of MV surgery (non-maze group).
      The maze group had less severe symptoms but larger left atrium, and AF of longer
      duration than the non-maze group. One surgeon performed all operations in both
      groups of patients. RESULTS: There were two early deaths in the maze group (4.5%)
      and one (2.2%) in the non-maze group. The duration of cardiopulmonary bypass
      (P=0.0001) and aortic crossclamping (P=0.0001) were greater in the maze group.
      Mean follow-up was 26+/-3 months in the maze group and 32+/-4 months in the non
      maze group, and was 100% complete. Three-year survival was 96+/-3% for the maze
      group compared to 85+/-7% for the non-maze group (P=0.16). At the latest follow
      up, 75% of the maze patients were in sinus rhythm compared to 36% of the non-maze
      patients (P=0.0004); 38% of the maze group were on coumadin postoperatively,
      compared to 69% in the non-maze group (P=0.003); and patients in the maze group
      were on fewer antiarrhythmic medications (P=0.0002). Three-year freedom from
      thromboembolic complications was 100% for the maze group compared to 83+/-7% for
      the non-maze group (P=0.03). CONCLUSIONS: In this retrospective study the maze
      procedure did not seem to increase operative mortality of MV surgery, was
      effective in eliminating atrial fibrillation, and reduced the risk of
      thromboembolic complications and the need for long-term anticoagulation after
      mitral valve repair or replacement with a bioprosthesis.

PMID- 11306310
TI  - The radiofrequency modified maze procedure. A less invasive surgical approach to
      atrial fibrillation during open-heart surgery.
AB  - OBJECTIVE: Patients with mitral valve disease and suffering of atrial
      fibrillation of more than 1 year's duration have a low probability of remaining
      in sinus rhythm after valve surgery alone. Intraoperative radiofrequency ablation
      was used as an alternative to simplify the surgical maze procedure. METHODS:
      Seventy-two patients with mitral valve disease, aged 63+/-11 years ranging from
      31 to 80 years, underwent valve surgery and radiofrequency energy applied
      endocardially, based on the maze III procedure to eliminate the arrhythmia. The
      right-sided maze was performed on the beating heart and the left-sided maze
      during aorta cross-clamping. RESULTS: Surgical procedures included mitral valve
      repair (n=38) or replacement (n=34) and in addition tricuspid valve repair
      (n=42), closure of an atrial septal defect (n=2) and correction of cor
      triatriatum (n=1). The left-sided maze needed 14+/-3 min extra ischemic time.
      There were two in-hospital deaths (2.7%) and three patients (4.2%) died during
      follow-up of 20+/-15 months. Among 67 surviving patients, 51 patients (76%) were
      in sinus rhythm, two patients (3%) had an atrial rhythm and eight patients (12%)
      had persistent atrial fibrillation or atrial flutter. Four patients had a
      pacemaker implanted, in one patient because of sinus node dysfunction. Doppler
      echocardiography in 64 patients demonstrated right atrial contractility in 89%
      and left atrial transport in 91% of patients. CONCLUSIONS: Intraoperative
      radiofrequency ablation of atrial fibrillation is an effective and less invasive
      alternative for the original maze procedure to eliminate atrial fibrillation.

PMID- 11306311
TI  - Sequential map-guided endocardial resection for ventricular tachycardia improves
      outcome.
AB  - OBJECTIVE: Surgery for ventricular tachycardias late after myocardial infarction
      is frequently associated with high mortality including sudden death, and
      arrhythmia recurrences. We examined our results of sequential map-guided
      endocardial resection at normothermia in patients with ventricular
      tachyarrhythmias late after myocardial infarction to assess the efficacy of this
      technique as well as the early and long-term outcome. METHODS: From 1995 to 1999,
      22 patients underwent normothermic sequential map-guided endocardial resection
      for ventricular tachyarrhythmias late after myocardial infarction. Mean age was
      61.2+/-6.5 years and left ventricular ejection fraction 32.5+/-8.7%. Adjunctive
      procedures included endoventricular patch repair of left ventricular aneurysm in
      21 patients, coronary artery bypass grafting in 15 patients, and mitral valve
      replacement in one patient. Inducibility of ventricular tachycardia was evaluated
      postoperatively and patients were treated with sotalol or defibrillator
      implantation. RESULTS: The intraoperative number of inducible different
      ventricular tachycardia morphologies was 4.0+/-2.7. More than one mapping
      resection sequence was needed in ten patients. In only one patient, sustained
      ventricular tachycardia was induced postoperatively, sotalol was not tolerated
      and a defibrillator was implanted. Five patients with inducible non-sustained
      ventricular tachycardia became non-inducible while on sotalol. There was one
      operative death (4.5%). During a median follow-up of 26 (1--62) months, there
      were neither cardiac deaths nor ventricular tachycardia recurrences. Two patients
      died from non-cardiac causes. Cumulative probability of survival at 5 years was
      0.83+/-0.09. CONCLUSIONS: Sequential map-guided endocardial resection at
      normothermia was associated with low operative mortality and low postoperative
      inducibility of sustained ventricular tachycardia. The selected therapeutic
      approach resulted in freedom of arrhythmia recurrence and cardiac mortality
      including sudden death, during long-term follow-up.

PMID- 11306312
TI  - Atrial fibrillation after coronary artery bypass grafting: does the type of
      procedure influence the early postoperative incidence?
AB  - OBJECTIVE: Atrial fibrillation (AF), the common postoperative complication, has
      been observed after coronary artery bypass grafting (CABG) in 7--40% of patients.
      Cardiopulmonary bypass (CPB), eliminated in off-pump operations (OPCABG) may
      decrease the incidence of AF, whereas the combination of CABG with heart valve
      replacement may result in more frequent postoperative atrial fibrillation. The
      aim of our study was to compare the early postoperative AF incidence rate during
      ICU stay in three groups of patients: after CABG, OPCABG, and CABG combined with
      valve replacement. MATERIAL AND METHODS: A prospective study of 906 consecutive
      patients was carried out between January 1999 and January 2000. Clinical profile
      of 906 patients, including factors having potential influence on postoperative AF
      did not showed any significant differences between the groups. The presence of
      arrhythmia history was the reason of excluding 85 patients from the statistical
      analysis. The observation was performed in each case during ICU-stay, using a HP
      system for continuous automated arrhythmia analysis. Early postoperative
      incidence of AF was recorded and compared between three groups of patients: 650
      after conventional CABG, 118 after OPCABG, and 53 after CABG combined with valve
      replacement. Chi-square and a Mann--Whitney tests, Statistica 5.0 PL were used
      for the statistical analysis. RESULTS: Atrial fibrillation occurred during the
      postoperative ICU stay in 9.8% of patients after CABG, in 10.2% after OPCABG, and
      in 21% after CABG combined with valve replacement. There was no significant
      difference between CABG and OPCABG groups (P=0.965). The confidence interval of
      the odds ratio ranges from 0.5 to 1.85. Consequently, an increased risk would be
      possible for both methods. We observed a statistically significant increase of
      the early postoperative atrial fibrillation incidence rate in patients after CABG
      combined with valve replacement, when compared with both CABG + OPCABG groups
      (P=0.005). CONCLUSIONS: (1) Atrial fibrillation is a common postoperative
      complication after myocardial revascularization procedures which prolongs ICU
      stay. (2) The study did not show that the incidence of postoperative AF is
      influenced by the technique of coronary artery bypass grafting: with or without
      CPB. (3) The prevalence of postoperative AF increase when CABG is combined with
      valve replacement.

PMID- 11306313
TI  - Fast track as a routine for open heart surgery.
AB  - OBJECTIVE: Evaluation of thoracic epidural analgesia (TEA), normothermic
      cardiopulmonary bypass (CPB) and normothermic blood cardioplegia as a routine
      procedure for fast track open heart surgery. METHODS: Consecutive patients
      (n=250, age 36--81 years, mean 63, M/F, ratio=4) were subjected to the
      combination of general anaesthesia using ultra-short acting opiates, TEA,
      normothermic CBP, normothermic whole blood cardioplegia. Operative procedures
      included coronary artery bypass grafting (CABG), valve replacement, combined CABG
      and valves, aortic aneurysm and Maze III. LVEF ranged 20--76%. Eighty percent
      were in Tuman score 0--5 and 20% in score >5. RESULTS: All patients were
      extubated within 10 min after skin closure. There was one myocardial infarction.
      Four percent were shortly treated with cathecholamines. Postoperative atrial
      fibrillation was noticed in 9.6%. Four transient cerebral ischemic events were
      encountered. No neurological disturbance related to the use of TEA was seen.
      Seven patients were reoperated because of bleeding. Blood transfusion was given
      to 6.4% of the patients. Mortality was 0.8%. CONCLUSIONS: The combined methods
      provides a way for routine immediate postoperative extubation, with low morbidity
      and short hospital stay.

PMID- 11306314
TI  - Single vessel revascularization with beating heart techniques -- minithoracotomy
      or sternotomy?
AB  - OBJECTIVE: The purpose of the study was to evaluate the best surgical approach in
      off-pump single vessel revascularization of the left anterior descending coronary
      artery (LAD). METHODS: In 256 patients a single left internal mammary artery
      (LIMA) to LAD bypass was performed with beating heart techniques through a left
      anterior minithoracotomy (minimally invasive direct coronary artery bypass
      (MIDCAB), n=129) or a full sternotomy (off-pump coronary artery bypass (OPCAB),
      n=127). RESULTS: In the OPCAB group, significantly more severe comorbidities
      (P=0.001) and redo-operations were noted (P<0.001). Conversion to sternotomy or
      CPB was necessary in five MIDCAB patients and one OPCAB patient. No
      cerebrovascular accident was seen in both groups. There was no hospital death in
      MIDCAB- and two deaths in OPCAB procedures (P=ns). There was a significant
      reduction in time of surgery (P=0.028) and coronary occlusion (P=0.009) in the
      OPCAB group. No differences in postoperative ventilation time, ICU stay and
      length of hospital stay were recorded between groups. Wound infections occurred
      in six MIDCAB patients (4.7%) and one OPCAB patient (0.8%). Early postoperative
      reoperation due to graft failure was necessary in three patients after MIDCAB and
      two patients after OPCAB (P=ns). Confirmed by angiography, the early graft
      patency rate was 96 and 98%, respectively (P=ns). CONCLUSIONS: Both beating heart
      techniques showed good results with low hospital mortality, low early
      complications and comparable angiographic results. Nevertheless, MIDCAB is a
      challenging technique as demonstrated by the longer times of surgery and coronary
      occlusion with a tendency towards a higher risk of conversion and wound
      infection. Thus, this technique should only be performed in selected patients
      with favourable coronary anatomy. Through a sternotomy approach, single vessel
      revascularization can be performed safely off-pump even in high-risk patients.

PMID- 11306315
TI  - Sternal wound complications after primary isolated myocardial revascularization:
      the importance of the post-operative variables.
AB  - OBJECTIVE: Select pre-, peri-, and post-operative variables, predictive for
      sternal wound complications (SWC), in a clinical setting. METHODS: We analyzed
      pre-, peri-, and post-operative data of 3815 patients who underwent a primary
      isolated bypass grafting. 100 patients (2.6%) had post-operative SWC. Unifactor
      and multifactor risk analysis, were used for statistical analysis. RESULTS:
      Unifactor analysis identified age (P=0.05), obesity (P=0.001), lung disease
      (P=0.001), extracorporeal circulation >100 min (P=0.02), graft choice (P=0.01),
      post-operative low cardiac output, reoperation, nephrological, pulmonary problems
      (P<0.001) as risk factors. Multifactor analysis, identified obesity (P=0.005),
      reoperation (P=0.01), nephrological (P=0.0001), pulmonary problems (P=0.001) and
      No-IMA-use (P=0.05) as independent predictors. Age <50 years (P=0.04) decreased
      the risk for SWC. There is, however, an interaction of the graft-use and the pre
      operative and post-operative predictors, that can mask the precise effect of the
      graft-use. CONCLUSION: Reoperation, nephrological and pulmonary problems are
      strong predictors, obesity and age independent preoperative risk factors for
      sternal wound complications.

PMID- 11306316
TI  - Animal model to compare the effects of suture technique on cross-sectional
      compliance on end-to-side anastomoses.
AB  - OBJECTIVE: An animal model has been developed to compare the effects of suture
      technique on the luminal dimensions and compliance of end-to-side vascular
      anastomoses. METHODS: Carotid and internal mammalian arteries (IMAs) were exposed
      in three pigs (90 kg). IMAs were sectioned distally to perform end-to-side
      anastomoses on carotid arteries. One anastomosis was performed with 7/0
      polypropylene running suture. The other was performed with the automated suture
      delivery device (Perclose/Abbott Labs Inc.) that makes a 7/0 polypropylene
      interrupted suture. Four piezoelectric crystals were sutured on toe, heel and
      both lateral sides of each anastomosis to measure anastomotic axes. Anastomotic
      cross-sectional area (CSAA) was calculated with: CSAA = pi x mM/4 where m and M
      are the minor and major axes of the elliptical anastomosis. Cross-sectional
      anastomotic compliance (CSAC) was calculated as CSAC=Delta CSAA/Delta P where
      Delta P is the mean pulse pressure and Delta CSAA is the mean CSAA during cardiac
      cycle. RESULTS: We collected a total of 1200000 pressure-length data per animal.
      For running suture we had a mean systolic CSAA of 26.94+/-0.4 mm(2) and a mean
      CSAA in diastole of 26.30+/-0.5 mm(2) (mean Delta CSAA was 0.64 mm(2)). CSAC for
      running suture was 4.5 x 10(-6)m(2)/kPa. For interrupted suture we had a mean
      CSAA in systole of 21.98+/-0.2 mm(2) and a mean CSAA in diastole of 17.38+/-0.3
      mm(2) (mean Delta CSAA was 4.6+/-0.1 mm(2)). CSAC for interrupted suture was 11 x
      10(-6) m(2)/kPa. CONCLUSIONS: This model, even with some limitations, can be a
      reliable source of information improving the outcome of vascular anastomoses. The
      study demonstrates that suture technique has a substantial effect on cross
      sectional anastomotic compliance of end-to-side anastomoses. Interrupted suture
      may maximise the anastomotic lumen and provides a considerably higher CSAC than
      continuous suture, that reduces flow turbulence, shear stress and intimal
      hyperplasia. The Heartflo anastomosis device is a reliable instrument that
      facilitates performance of interrupted suture anastomoses.

PMID- 11306317
TI  - Phenoxybenzamine is more effective and less harmful than papaverine in the
      prevention of radial artery vasospasm.
AB  - OBJECTIVES: There is an increasing use of arterial conduits for coronary artery
      bypass grafting, and the radial artery is commonly used as the third graft. The
      major drawback of the radial artery is its proclivity to spasm. Both papaverine
      and phenoxybenzamine have been recommended as topical vasodilators in clinical
      practice. We compared the efficacy of both drugs to prevent radial artery spasm
      and their ability to preserve endothelial function. METHODS: The ability of both
      drugs to prevent alpha-adrenoreceptor mediated constriction was tested in vitro
      in an organ bath in radial artery segments obtained from 20 patients. Vessel
      viability was determined by potassium (K(+)) constriction, and endothelial
      function was assessed by observing endothelium-dependent relaxation by a
      synthetic analogue of acetylcholine, carbachol. RESULTS: Papaverine consistently
      abolished and prevented spasm for up to a maximum of 30 min in all segments. In
      contrast, phenoxybenzamine consistently abolished and prevented radial artery
      spasm in all segments for at least 6 h. Whereas papaverine damaged the
      endothelium of 70% of vessels, there was no evidence of endothelial damage in any
      arterial segments after exposure to phenoxybenzamine. CONCLUSIONS:
      Phenoxybenzamine more effectively prevents alpha-adrenoreceptor mediated spasm of
      the human radial artery than papaverine. It is also less harmful to the
      endothelium.

PMID- 11306318
TI  - Prevention of neointimal proliferation by immunosuppression in synthetic vascular
      grafts.
AB  - OBJECTIVE: Immunosuppressive agents have been proposed to reduce neointimal
      hyperplasia in synthetic vascular grafts. Thus, the purpose of the present study
      was to evaluate the safety and efficacy of rapamycins (systemic vs. local vs.
      oral administration) and mycophenolate mofetil (MMF) to reduce intimal
      hyperplasia in infrarenal synthetic vascular grafts of the rat. METHODS: Fifty
      four Wistar rats (250 g) completed the study after a synthetic vascular graft
      (ePTFE, Gore-tex, 2 mm diameter, 10 mm length) was implanted end-to-end in the
      infrarenal aorta. The animals were divided into three groups: group 1 consisted
      of 12 control animals, group 2 consisted of 37 rats receiving rapamycins, either
      per os (RAD, 1.5 or 3 mg/kg), intraperitoneally (RPM, 1.5 or 3 mg/kg) or locally
      (RPM soaking of the graft); and in group 3 (n=5), MMF (40 mg/kg) was administered
      orally. The animals were followed weekly with weight controls and signs of
      toxicity for 30 (n=37) and 60 (n=17) days, respectively. All animals were
      sacrificed and underwent histological examination at completion of the study.
      RESULTS: All animals survived in groups 1 and 3, but five died in group 2. The
      weight gain was normal in all groups, except for the subgroup 2a receiving high
      dose rapamycins orally. All rats in group 3 suffered from diarrhea, whereas
      animals receiving high dose rapamycins showed toxic signs (hair loss, wound
      healing problems). Histological examination showed a significant increase in
      intimal hyperplasia in group 1 (0.03+/-0.01 and 0.14+/-0.05 microm after 30 and
      60 days, respectively; P<0.01). Rapamycins in either application or dosage had no
      significant effect on intimal hyperplasia. CONCLUSIONS: Local or systemic
      administration of rapamycins has no effect on intimal hyperplasia in synthetic
      vascular grafts. In contrast, toxic signs with weight loss were observed in
      animals treated with high dose rapamycins, but not in those treated with MMF.
      Thus, in the rat model, immunosuppression with rapamycins or MMF cannot be
      recommended for the prevention of intimal hyperplasia in the synthetic vascular
      graft model.

PMID- 11306319
TI  - Differential effect of preconditioning on post-ischaemic myocardial performance
      in the absence of substantial infarction and in extensively infarcted rat hearts.
AB  - OBJECTIVES: There is controversy concerning the beneficial effects of ischaemic
      preconditioning during short periods of ischaemia (stunning). The aim of the
      study was to investigate post-ischaemic myocardial performance after various
      periods of ischaemia in both non-preconditioned and preconditioned hearts and to
      compare these results with infarct volume estimation. METHODS: Isolated perfused
      rat hearts were subjected to various periods of sustained ischaemia (15, 20, 30,
      and 45 min). Haemodynamic parameters, infarct size and lactate dehydrogenase
      (LDH) leakage were recorded in both preconditioned and non-preconditioned hearts.
      RESULTS: After 15 min of ischaemia, preconditioned hearts revealed significantly
      lower developed pressure than non-preconditioned hearts (80+/-4.1 vs. 95+/-0.3%,
      P=0.02). In the 20 min ischaemia group, preconditioning resulted in non
      significantly lower developed pressure (76+/-3.1% in preconditioned hearts vs.
      87+/-5.3% in non-preconditioned hearts, P=0.11). In these groups infarct volume
      was small and not different between non-preconditioned and preconditioned hearts.
      After 30 min of ischaemia, preconditioning significantly improved developed
      pressure (66+/-3.1% in preconditioned and 44+/-5% in non-preconditioned hearts,
      P=0.002). LDH leakage was significantly higher in non-preconditioned hearts
      compared with preconditioned hearts (16+/-2.3 vs. 9.0+/-1.3, P=0.04), whereas
      infarct volume was not (12.5+/-0.8 and 9.8+/-1.5, respectively, P=0.1). Non
      preconditioned hearts of this group, subjected to inotropic stimulation at the
      end of reperfusion, responded poorly. Significantly higher developed pressure was
      attained by preconditioned hearts (150+/-3.1 vs. 123+/-7.5%, P=0.01). After 45
      min of ischaemia, preconditioning resulted in 69% limitation of infarct volume
      (P<0.0001) and 53% reduction in LDH release (P=0.009). Developed pressure was
      57+/-8.5% in preconditioned hearts and 32+/-4.5% in non-preconditioned hearts
      (P=0.02). CONCLUSIONS: When ischaemic insult results in minimally lethal
      injuries, preconditioned hearts do not have the advantage of not being prone to
      stunning rather than non-preconditioned. If ischaemic insult is potentially able
      to produce extensive infarction, improvement in post-ischaemic myocardial
      function is mainly due to infarct size limitation evoked by preconditioning.

PMID- 11306320
TI  - Comparison of histopathologic effects of carnitine and ascorbic acid on
      reperfusion injury.
AB  - OBJECTIVE: Reperfusion injury can be seen after acute arterial occlusion, acute
      myocardial infarctus and during open heart surgery and vascular surgery.
      Protective effects of ascorbic acid and carnitine on reperfusion damage were
      tested and compared using histopathologic examination on ischemia model in the
      rabbit hind limb. METHODS: Four groups (each containing ten animals) were used.
      In group I (G1), only anesthesia was administered and a biopsy was taken from the
      soleus muscle after 6 h. In group II (G2), group III (G3), and group IV (G4),
      after induction of anesthesia, arterial blood circulation of right posterior
      extremity was blocked by a tourniquet proximally. After four hours of ischemia,
      just before releasing of tourniquet, physiologic saline solution, sodium
      ascorbate (Redoxan) and L-carnitine (Carnitine) were administered intravenously
      to G2, G3 and G4, respectively. Following 2 h of reperfusion, biopsies were taken
      from soleus muscles. All of the biopsy slides were observed under the light
      microscope from the aspect of six different histopathologic criteria (loss of
      striation, nuclear centralisation, formation of ring and/or splitting, changing
      on diameters of muscle fibers, necrosis and minimal fibrosis) of ischemic muscle.
      RESULTS: Ischemic change criteria were seen less frequency in both vitamin C and
      carnitine groups compared to the control and placebo groups. However, this
      protective effect was statistically significant only for the aspect of segmental
      necrosis, centralization of nuclei and diameter change parameters in G3 and in
      G4. When G3 and G4 were compared, the differences on protective effects were
      significant only from the aspect of fibrosis (P<0.001) and changing on diameter
      of the fibers (P<0.001). CONCLUSIONS: Both sodium ascorbate and carnitine are
      effective on reducing the reperfusion injury in skeletal muscle. But when we
      compared these two agents to each other, we found that carnitine seems a little
      more protective on our experimental model.

PMID- 11306321
TI  - Smart suction device for less blood trauma: a comparison with Cell Saver.
AB  - OBJECTIVE: The major source of hemolysis during cardiopulmonary bypass remains
      the cardiotomy suction and is primarily due to the interaction between air and
      blood. The Smart suction system involves an automatically controlled aspiration
      designed to avoid the mixture of blood with air. This study was set-up to compare
      this recently designed suction system to a Cell Saver system in order to
      investigate their effects on blood elements during prolonged intrathoracic
      aspiration. METHODS: In a calf model (n=10; mean weight, 69.3+/-4.5 kg), a
      standardized hole was created in the right atrium allowing a blood loss of 100
      ml/min, with a suction cannula placed into the chest cavity into a fixed position
      during 6 h. The blood was continuously aspirated either with the Smart suction
      system (five animals) or the Cell Saver system (five animals). Blood samples were
      taken hourly for blood cell counts and biochemistry. RESULTS: In the Smart
      suction group, red cell count, plasma protein and free hemoglobin levels remained
      stable, while platelet count exhibited a significant drop from the fifth hour
      onwards (prebypass: 683+/-201*10(9)/l, 5 h: 280+/-142*10(9)/l, P=0.046). In the
      Cell Saver group, there was a significant drop of the red cell count from the
      third hour onwards (prebypass: 8.6+/-0.9*10(12)/l, 6 h: 6.3+/-0.4*10(12)/l,
      P=0.02), of the platelet count from the first hour onwards (prebypass: 630+/
      97*10(9)/l, 1 h: 224+/-75*10(9)/l, P<0.01), and of the plasma protein level from
      the first hour onwards (prebypass: 61.7+/-0.6 g/l, 1 h: 29.3+/-9.1 g/l, P<0.01).
      CONCLUSIONS: In this experimental set-up, the Smart suction system avoids damage
      to red cells and affects platelet count less than the Cell Saver system which
      induces important blood cell destruction, as any suction device mixing air and
      blood, as well as severe hypoproteinemia with its metabolic, clotting and
      hemodynamic consequences.

PMID- 11306322
TI  - Endobronchial lipoma.

PMID- 11306323
TI  - Intracardiac foreign body: a sewing needle in right ventricle.

PMID- 11306324
TI  - Ectopic mediastinal pancreas.
AB  - Ectopic localisation of the pancreas is not an uncommon entity, but it is mostly
      seen in the gastrointestinal tract. Herein we report a 45-year-old woman with a
      cyst containing pancreatic tissue in the mediastinum. The English literature
      reveals only three previous cases of this extremely rare localisation of the
      pancreas.

PMID- 11306325
TI  - Metastatic granulosa cell tumour of the diaphragm 15 years after the primary
      neoplasm.
AB  - We present the case of a female patient who complained of dyspnoea and was found
      to have a pleural effusion. A tumour involving the right diaphragm was seen on CT
      and after excision this was shown to be a recurrent granulosa cell tumour, 15
      years after the original ovarian lesion had been treated by oophrectomy and
      radiotherapy. The case and literature relating to such a rare intra-thoracic
      metastatic tumour is discussed.

PMID- 11306326
TI  - Castleman's disease: unusual intrathoracic localization.
AB  - Chest-wall is a rare localization of Castleman's disease. The tumour is often
      diagnosed after onset of non-specific thoracic symptoms but can be occasionally
      detected in asymptomatic patients. Surgical removal is curative and should be
      conservative with no recurrences. We report a new case and we review the
      international literature.

PMID- 11306327
TI  - Role of pre-operative assessment in the surgical management of leiomyoma extended
      to the right heart chambers: a compendium of information from isolated reports.
AB  - Recurrent intravenous leiomyoma extending to the right heart chambers is
      extremely rare. A large range of surgical techniques and approaches (i.e. two
      step procedure, hypothermia and circulatory arrest) have been previously
      described. We report a recent case where the tumour was excised in a one-step
      procedure under normothermic cardiopulmonary bypass. This report associated to a
      comprehensive literature review allows us to discuss the role of pre-operative
      assessment and to propose refinement of surgical techniques according to the
      anatomy of the tumour.

PMID- 11306328
TI  - Budd--Chiari syndrome and heparin-induced thrombocytopenia.
AB  - We report on a patient suffering from Budd--Chiari disease who developed heparin
      induced thrombocytopenia preoperatively. Dorsocranial liver resection and
      hepatoatrial anastomosis were performed with the extracorporeal circulation and
      perioperative anticoagulation was achieved with r-hirudin. Surprisingly, thrombus
      formation was observed in the venous reservoir although ACT was 590 s and aPTT 55
      s. An additional bolus of hirudin and rinsing the reservoir allowed unproblematic
      discontinuation of the cardiopulmonary bypass.

PMID- 11306329
TI  - A dual strategic approach to mega-aortic aneurysms.
AB  - Staged resection of mega-aortas with Borst's two-stage elephant trunk (ETK) is
      the gold standard but has a higher mortality and morbidity compared to single
      segment repair. We report the first case of combined surgical and covered-stent
      approach in Europe. Location and dilatation of the proximal landing zone accounts
      for the majority of failures in covered-stenting but an ETK is stable, easy to
      localise and gives an excellent seal. In high-risk cases where surgical resection
      is not offered, stenting is an option. The lack of a thoracotomy is an advantage
      in often-frail patients recovering from stage-I and shortens ITU-stay. Therefore,
      a combined approach is an acceptable alternative in selected individuals.

PMID- 11306330
TI  - Proximal pseudoaneurysm of ascending-abdominal aortic bypass.
AB  - Proximal pseudoaneurysm of ascending-abdominal aortic bypass is an uncommon
      surgical disease. We report a repair of complete detachment of proximal
      anastomosis of the ascending-abdominal aortic bypass in a 68-year-old man that
      underwent surgery in 1988 for chronic descending thoracic aortic aneurysm treated
      with thromboesclusion technique. The clinical, diagnostic, and operative aspects
      are discussed.

PMID- 11306331
TI  - Thrombotic formations within the aortic arch as source of embolization in
      patients with coagulopathia.
AB  - Thrombotic formations on atherosclerotic lesions of the thoracic aorta are
      potential sources of cerebral and systemic embolization. Especially younger
      patients without calcifications of atherosclerotic plaques or coagulation
      disorders have a higher risk for embolization. Magnetic resonance imaging and
      transesophageal echocardiography are the diagnostic methods of choice. As an
      alternative to anticoagulation surgical therapy is indicated to prevent severe
      brain damage or multiorgan failure in patients with mobile thrombotic formations.
      Herein we describe two patients in whom successful surgical treatment was
      performed in deep hypothermic circulatory arrest by excision of the aortic arch
      atheroma.

PMID- 11306332
TI  - Lessons from anticancer research might provide new insights into mechanisms of
      hormone action.
AB  - The extent to which specific anticancer drugs induce apoptosis in tumors
      frequently predicts the success of chemotherapy for a particular type of cancer.
      Recent results from experiments designed to evaluate drug-induced apoptosis in
      colon cancer cells revealed that the levels of BCL-2-related apoptotic suppressor
      proteins were dramatically reduced compared with those of pro-apoptotic proteins.
      In the case of nonsteroidal anti-inflammatory drugs, this might be a consequence
      of inhibition of the cyclooxygenase-mediated production of prostaglandins.

PMID- 11306333
TI  - Cranial irradiation and central hypothyroidism.
AB  - Cranial irradiation causes thyrotropin (TSH)-releasing hormone (TRH) secretory
      abnormalities. TRH deficiency leads to abnormal glycosylation of TSH alpha and
      beta subunits and loss of the normal circadian pattern of TSH secretion (low in
      the afternoon, a surge in the evening, higher at night). This disruption results
      in either mixed hypothyroidism (raised TSH with abnormal secretory kinetics) or
      central hypothyroidism (abnormal secretory kinetics without raised TSH). Although
      primary hypothyroidism is more common in the general population and cancer
      survivors, the cumulative incidence of central and mixed hypothyroidism is high
      during the ten years after cranial irradiation. Monitoring for decline in free
      thyroxine (FT(4)) and rise in serum TSH, and early recognition using TSH surge
      and TRH tests, are clinically valuable. Early thyroid hormone replacement therapy
      to achieve serum FT(4) in the upper half of the normal range is crucial for
      maintaining optimal health and growth in cancer survivors.

PMID- 11306334
TI  - Apparent mineralocorticoid excess.
AB  - Apparent mineralocorticoid excess (AME) is a potentially fatal genetic disorder
      causing severe juvenile hypertension, pre- and postnatal growth failure,
      hypokalemia and low to undetectable levels of renin and aldosterone. It is caused
      by autosomal recessive mutations in the HSD11B2 gene, which result in a
      deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2). The 11
      beta-HSD2 enzyme is responsible for the conversion of cortisol to the inactive
      metabolite cortisone and, therefore, protects the mineralocorticoid receptors
      from cortisol intoxication. In 1998, a mild form of this disease was reported,
      which might represent an important cause of low-renin hypertension. Early and
      vigilant treatment might prevent or improve the morbidity and mortality of end
      organ damage.

PMID- 11306335
TI  - Glycodelins.
AB  - Glycodelin is a major glycoprotein that is synthesized in the endometrium in
      response to progesterone and relaxin exposure. Endometrium-derived glycodelin-A
      has contraceptive and immunosuppressive properties. Glycodelin is absent from the
      endometrium during the fertile periovulatory phase, but is synthesized in this
      tissue during the peri-implantation phase and is abundant during the last week of
      the luteal phase. Changes in local and/or circulating glycodelin concentrations
      have been observed in women with reproductive disorders. The chemical
      modification of glycodelins has resulted in compounds with antiviral activity.

PMID- 11306336
TI  - Ghrelin: discovery of the natural endogenous ligand for the growth hormone
      secretagogue receptor.
AB  - Growth hormone (GH) secretagogues (GHSs) are small synthetic molecules that act
      through a specific G-protein-coupled receptor (GPCR) called GHS-R. Until the
      recent identification of 'ghrelin' from rat and human stomachs, GHS-R was an
      orphan receptor (i.e. had no known natural ligand). Ghrelin is a 28-amino acid
      peptide with an essential n-octanoyl modification at Ser3. This peptide is found
      in the secretory granules of X/A-like cells, whose hormonal products and
      physiological functions have not been previously clarified. The discovery of
      ghrelin indicates that the release of GH from the pituitary might be regulated
      not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from
      the stomach and hypothalamus.

PMID- 11306337
TI  - Novel glucocorticoid receptor coactivator effector mechanisms.
AB  - Glucocorticoids regulate numerous distinct physiological processes, most of which
      rely on the ability of the hormone-bound glucocorticoid receptor (GR) to change
      the expression of target genes in a cell- and promoter-dependent manner. The
      transcriptional activity of GR depends on coactivators that regulate
      transcription by remodeling chromatin or by facilitating the recruitment of the
      basal transcriptional machinery. Coactivators are often part of multiprotein
      complexes that are not specific for GR but also mediate the activity of other
      nuclear receptors (NRs) and unrelated transcription factors. Surprisingly, recent
      results reveal that the activity of coactivators might contribute to the
      receptor, promoter and cell specificity of NR action. The emerging picture shows
      coactivators as flexible, but precise, coordinators of complex and dynamic
      networks, in which transcriptional regulation by GR and other NRs is linked to
      other signaling pathways.

PMID- 11306338
TI  - The TRAP/SMCC/Mediator complex and thyroid hormone receptor function.
AB  - The TRAP/SMCC/Mediator complex is a mammalian transcriptional regulatory complex
      that contains over 25 polypeptides and is, in part, phylogenetically conserved.
      It was originally isolated as a thyroid hormone receptor (TR)-associated protein
      (TRAP) complex that mediates TR-activated transcription from DNA templates in
      conjunction with the general transcription machinery, and probably acts in vivo
      after the action of other receptor-interacting coactivators involved in chromatin
      remodeling. Subsequently, the TRAP complex was identified as a more broadly used
      coactivator complex for a wide variety of activators. The TRAP220 subunit
      mediates ligand-dependent interactions of the complex with TR and other nuclear
      receptors; and genetic ablation of murine TRAP220 has revealed that it is
      essential both for optimal TR function and for a variety of early developmental
      and adult homeostasis events in mice, but not for cell viability per se.

PMID- 11306339
TI  - A qualitative study of subject recruitment for familial cancer research.
AB  - PURPOSE: Familial epidemiological studies of cancer raise familiar ethical issues
      relating to informed consent and recruitment of participants. When the family is
      the unit of study, however, additional complexity arises. Educating and
      recruiting participants must be tailored to the relatives', as well as the
      proband's needs. An understanding of the prospective participants' concerns will
      aid the development of strategies for recruitment and will facilitate informed
      and voluntary consent. In the present study, qualitative methods were used to
      investigate these issues. METHODS: Focus groups with cancer patients, relatives
      of cancer patients, and individuals from the general population were separately
      conducted to identify issues that concern people who are asked to participate in
      family studies. RESULTS: Many of the issues which arose in the course of the
      focus group discussions were similar to those in any study. Yet, some of the
      themes emerging from the discussions were specific to familial research. In
      particular, participants expressed that the study should be endorsed by a trusted
      and familiar source; group discussions might facilitate the consent process; the
      benefit of the research should be clear and personal, as well as benefit the
      participants' family members; risks of participation should be explicit (e.g.,
      insurance discrimination); and education about the disease and its familial
      nature would maintain commitment to the study. Finally, participants expressed
      concerns about being approached by programs to facilitate the identification and
      recruitment of other family members for research on family health issues.
      CONCLUSIONS: Findings from this study will aid future familial studies in
      developing a protocol that both adequately informs potential participants of the
      nature of familial research and maximize participation.

PMID- 11306340
TI  - Active and passive smoking and risk of colds in women.
AB  - PURPOSE: To evaluate the association between active and passive smoking and
      frequency of colds in women. METHODS: Data on cigarette smoking and frequency and
      duration of colds were analyzed in the Women's Health Study (WHS), a randomized,
      double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the
      primary prevention of cardiovascular disease and cancer among 39,876 female
      health professionals. RESULTS: After adjustment for age, body-mass index,
      prevalence of asthma and chronic lung diseases, alcohol intake, physical
      activity, and multivitamin use, current heavy smokers had no appreciable increase
      in the frequency of colds (relative risk (RR) for >or= 3 versus no colds in the
      past year, 1.05; 95% confidence interval (CI), 0.80-1.39), but a significantly
      increased risk of prolonged colds (RR for colds of > 7 vs. 1-3 days, 2.53; 95%
      CI, 1.95-3.29). There was no difference in the number of days confined to home.
      Nonsmoking women passively exposed to cigarette smoke had a slightly increased
      risk of both more frequent colds (RR, 1.33; 95% CI, 1.18-1.51) and more prolonged
      colds during the previous year (RR, 1.12; 95% CI, 0.99-1.27). CONCLUSIONS: Women
      who are currently heavy smokers are at increased risk of having colds with longer
      duration compared with nonsmokers. Nonsmoking women passively exposed to
      cigarette smoking are at slightly increased risk of having more frequent and
      longer colds than nonsmoking women not exposed to passive smoke.

PMID- 11306341
TI  - Smoking, other risk factors and fibrinogen levels. evidence of effect
      modification.
AB  - PURPOSE: Recent investigations have indicated that smoking may act as an
      important modifier of the risk associated with dyslipidemia. We hypothesized as a
      potential mechanism that smoking modifies the association between traditional
      risk factors of early atherosclerosis, such as dyslipidemia, hypertension, or
      diabetes, with fibrinogen, a risk factor more closely related to plaque
      progression and thrombosis. METHODS: The sample for this cross-sectional study,
      was collected from the MONICA Augsburg population survey of 1989/90 and included
      1840 men and 1784 women, aged 25 to 64 years. Traditional risk factors
      hypertension, diabetes mellitus, and dyslipidemia were assessed by personal
      interviews, and medical examinations. Plasma fibrinogen concentration was
      determined by nephelometry. Effect modification was assessed by stratified
      analyses and tests for statistical interaction. RESULTS: Fibrinogen levels were
      higher in women than in men and, after adjustment for potential confounders,
      higher in smokers than in nonsmokers (each p < 0.001). The effect of smoking was
      greater in men (p < 0.001). The elevation of mean adjusted fibrinogen levels
      associated with hypertension or with diabetes in men was significantly higher in
      smokers as compared to nonsmokers (test for interaction, p < 0.001). By contrast,
      smoking in women showed significantly stronger impacts only with regard to the
      association of dyslipidemia and fibrinogen (p < 0.001). Comparing groups of
      subjects with increasing numbers of concomitant risk factors, stratified
      according to their smoking status, effect modification by smoking was
      particularly evident in male participants with two or more risk factors. Numbers
      of women with more than one risk factor and smoking were too low for analysis.
      CONCLUSIONS: We demonstrate that smoking contributes more than additively to the
      strong influences of single and combined traditional risk factors on fibrinogen
      levels. These data confirm that smoking is a dominant determinant of fibrinogen
      levels in the general population.

PMID- 11306342
TI  - Presenting manifestations, cigarette smoking, and detection bias in age at
      diagnosis of lung cancer.
AB  - PURPOSE: To examine the possible role of detection bias in the association
      between amount of cigarette smoking and age at diagnosis of lung cancer. The bias
      can occur because primary lung cancer can often escape detection during life and
      will be found (if at all) as a "necropsy surprise" unless a diagnostic workup is
      provoked by such presenting manifestations as hemoptysis and a localized chest
      lesion. The necropsy surprises will be reduced and the reported rates of pre
      mortem incidence will be raised if a cigarette smoking history also acts as a
      diagnostic incentive. METHODS: This possibility was examined in a case series of
      1266 patients whose primary lung cancer had been carefully classified according
      to diverse features at the time of presentation. For the total case group and for
      pertinent clinical, anatomic, and demographic subgroups, we then examined the
      trends for age at diagnosis in relation to amount of cigarette smoking. RESULTS:
      The overall age at diagnosis (median = 63 years; mean = 61.2) remained
      essentially similar in five ordinal groups of Tumor, Nodes, Metastases (TNM) and
      four of five Clinical Severity stages, but had an inverse monotonic gradient in
      six ordinal groups of customary cigarette smoking [from none to >2 packs per day
      (ppd)]. Because an earlier age of discovery can be explained by either etiologic
      or detection-bias roles for heavier smoking, its impact was checked in subgroups
      with and without diagnostically provocative manifestations. In localized lesions,
      the smoking-age gradient vanished if suspicious "indicator" symptoms were
      present, but persisted if they were absent. Regardless of symptoms, the age
      gradient was strengthened in non-localized cancer lesions where smoking might
      particularly point to a primary diagnostic source in the lung. CONCLUSIONS:
      Detection bias may play a distinctive, although often overlooked, role in the
      work-up decisions that precede and lead to a diagnosis of lung cancer.

PMID- 11306343
TI  - Cancer risk at sites other than the breast following augmentation mammoplasty.
AB  - PURPOSE: There has been limited investigation of cancer risk other than breast
      cancer among patients with breast implants, despite some clinical and laboratory
      evidence suggesting links with certain cancer sites, including hematopoietic and
      connective tissue malignancies. METHODS: A retrospective cohort study of 13,488
      patients who received cosmetic breast implants at 18 plastic surgery practices in
      six geographic areas was conducted to assess long-term health effects. After an
      average of 12 years of follow-up, questionnaires were administered to subjects
      located and alive (78% of eligible population). Attempts were made to obtain
      death certificates for deceased subjects and medical verification for all
      reported cancers. Expected numbers of cancers were derived using general
      population cancer incidence rates and an internal comparison series of 3936
      patients who received other types of plastic surgery at the same practices as the
      implant patients. RESULTS: A total of 359 malignancies was observed versus 295.95
      expected based on general population rates, resulting in a standardized incidence
      ratio (SIR) of 1.21 [95% confidence interval (CI) 1.1-1.4]. Individual
      malignancies for which incidence was significantly elevated included cancers of
      the stomach (SIR = 2.65), cervix (SIR = 3.18), vulva (SIR = 2.51), brain (SIR =
      2.16), and leukemia (SIR = 2.19). No excess risks were observed for other
      hematopoietic malignancies, including multiple myeloma. The internal analyses,
      however, based on cancer rates derived among the comparison patients, showed no
      increased cancer risk among the implant patients [relative risk (RR) = 1.00, 95%
      CI 0.8-1.2], as well as no statistically significant elevations for most
      individual sites. Cervical cancer continued to be elevated (RR = 1.78), although
      to a lesser extent than in the external analyses, while the risk for respiratory
      cancers was higher (RR = 2.40). Non-significant elevations in risk persisted in
      this analysis for liver cancer (RR = 2.65), brain cancer (RR = 2.83), and
      leukemia (RR = 1.83). Many of the cancers showing excesses were defined on the
      basis of death certificates, requiring caution in interpretation. The histologies
      of the leukemias were quite varied, which makes a biologic relationship appear
      unlikely. However, respiratory cancers showed some evidence of increasing risk
      with follow-up time and both respiratory and brain cancers were elevated in the
      mortality analyses. CONCLUSIONS: Although excesses of cervical and vulvar cancer
      among implant patients might be attributable to lifestyle factors, reasons for
      excesses of respiratory and brain cancers were less apparent.

PMID- 11306344
TI  - Variation in mammographic breast density by race.
AB  - PURPOSE: Because of the observed racial differences in risk of developing breast
      cancer, the authors conducted a study to determine the variation in breast
      density, a strong predictor of breast cancer risk, by race and age. METHODS:
      Study subjects were women enrolled in Group Health Cooperative of Puget Sound,
      Seattle, WA, aged 20-79 years, who had a screening mammogram between 6/1/96 and
      8/1/97. Women with increased breast density (BI-RADS "heterogeneously dense" and
      "extremely dense") (n = 14,178) were compared to those with fatty breasts (BI
      RADS "almost entirely fat" and "scattered fibroglandular tissue") (n = 14,323).
      Logistic regression was used with adjustment for age, parity, age at first birth,
      menopausal status, current use of hormone replacement therapy, and body mass
      index. RESULTS: The odds ratio (OR) for having dense breasts versus fatty
      breasts, comparing Asian to White women, increased from 1.2 [95% confidence
      interval (CI) 0.9-1.6] for women age <45 to 1.6 (95% CI 1.3-2.2) for women over
      65. Conversely, the OR for Black compared to White women was highest for the
      women age 65 and younger (OR 1.7 (1.2-2.3), 1.3(1.0-1.7), and 1.7 (1.2-2.3) for
      women age <45, 46-55, and 56-65, respectively), whereas Black women over 65 had
      similar density as Whites. Hispanic women had similar density compared to Whites
      for all ages. CONCLUSIONS: These racial differences in breast density generally
      do not conform to differences in race and age-specific breast cancer incidence
      rates.

PMID- 11306345
TI  - Referral to autopsy: effect of antemortem cardiovascular disease: a population
      based study in Olmsted County, Minnesota.
AB  - PURPOSE: Autopsy studies can provide insight into disease trends and their
      determinants, including data on the prevalence of atherosclerosis. However, such
      studies are subject to autopsy bias, which limits their generalizability to the
      source population. The impact of this bias on autopsy based estimates of time
      trends in heart disease prevalence is unknown. To report on the trends over time
      in autopsy rates in Olmsted County, MN, to examine the association between
      clinical diagnoses of cardiovascular diseases (CVDs) and referral to autopsy and
      how this association may have changed over time. METHODS: We examined the trends
      in autopsy rates between 1979 and 1994 in Olmsted County, and the association
      between antemortem characteristics including cardiovascular diagnoses and autopsy
      referral. RESULTS: From 1979 to 1994, a total of 9110 residents died in Olmsted
      County. The average annual autopsy rate was 30%. Autopsy rates declined from 36%
      in 1979 to 23% in 1994, corresponding to an average decline of 0.6%/year (p <
      0.01). Referral to autopsy was positively associated with younger age, male sex,
      in-hospital place of death, antemortem diagnoses of myocardial infarction (MI) or
      peripheral vascular disease (PVD), and earlier calendar period. There was no
      evidence of an interaction between calendar period and any of these predictor
      variables. Antemortem diagnosis of heart failure was associated with a decrease
      in the odds of referral to autopsy over time as compared to persons without such
      diagnosis. CONCLUSIONS: In Olmsted County, autopsy rates, although declining over
      time, have remained on average approximately 30%. Antemortem diagnoses of MI or
      PVD are associated with autopsy referral but this association did not change over
      time. While the greater decline overtime in the use of autopsy observed among
      decedents with an antemortem diagnosis of congestive heart failure (CHF) deserves
      further studies, the present findings reduce the concern for bias of time trends
      in the prevalence of atherosclerosis by changes in the clinical characteristics
      of decedents referred to autopsy.

PMID- 11306346
TI  - Birth cohort evidence of population influences on blood pressure in the United
      States, 1887-1994.
AB  - PURPOSE: Mean blood pressure (BP) has declined in the U.S. for several decades.
      It is unknown to what extent this decline was due to treatment of persons with
      recognized high BP or to population-wide influences on BP. Treatment would shift
      only the highest values lower, whereas, population-wide influences on BP would
      shift the entire distribution downward. METHODS: We examined changes in the
      distributions of systolic and diastolic BP (SBP, DBP) across birth cohorts born
      between 1887 and 1975 in 52,646 individuals examined in the National Health (and
      Nutrition) Examination Surveys between 1960 and 1994. The BP distributions were
      estimated as functions of age and birth-year to examine changes between birth
      cohorts. We postulated that the age-adjusted 10th, 50th and 90th percentiles of
      SBP and DBP had decreased in more recent versus earlier birth cohorts. RESULTS:
      The series of birth cohorts exhibited successively lower SBP and DBP at low,
      middle and high percentiles. In general, the 10th percentile of SBP decreased
      approximately 1.19 mmHg per decade of birth-year, whereas the 50th percentile
      decreased 2.40 mmHg per decade, and the 90th percentile decreased 4.62 mmHg per
      decade. A similar pattern of results was seen for DBP. CONCLUSIONS: The entire
      distribution of both SBP and DBP shifted downward. The downward shifts at the
      50th percentile and below unequivocally demonstrate a strong prevention effect in
      the U.S. population during the period 1887 through 1975. This epidemiologic
      analysis indicates that population-wide influences can alter favorably the
      distribution of BP throughout the whole population.

PMID- 11306347
TI  - Functional and dysfunctional roles of quadruplex DNA in cells.
AB  - A number of biological roles have been proposed for quadruplex, also referred to
      as G4 or tetraplex, DNA. The presence of quadruplex DNA may lead to errors in
      some biological processes and be required in others. Proteins that interact with
      quadruplex DNA have been identified including those that cause Bloom's and
      Werner's syndromes. There are small molecules that specifically bind to
      quadruplex DNA, inhibit telomerase, and are cytotoxic towards tumor cells
      indicating a role for quadruplex DNA in telomere function. It is now possible to
      make testable proposals for the possible biological implications of quadruplex
      DNA in replication, transcription, and recombination as well as possible routes
      to therapeutic intervention.

PMID- 11306348
TI  - Characterizing Class I WW domains defines key specificity determinants and
      generates mutant domains with novel specificities.
AB  - INTRODUCTION: WW domains are small protein interaction modules found in a wide
      range of eukaryotic signaling and structural proteins. Five classes of WW domains
      have been annotated to date, where each class is largely defined by the type of
      peptide ligand selected, rather than by similarities within WW domains. Class I
      WW domains bind Pro-Pro-Xxx-Tyr containing ligands, and it would be of interest
      to determine residues within the domains that determine this specificity.
      RESULTS: Fourteen WW domains selected Leu/Pro-Pro-Xxx-Tyr containing peptides
      ligands via phage display and were thus designated as Class 1 WW domains. These
      domains include those present in human YAP (hYAP) and WWP3, as well as those
      found in ubiquitin protein ligases of the Nedd4 family, including mouse Nedd4
      (mNedd4), WWP1, WWP2 and Rsp5. Comparing the primary structures of these WW
      domains highlighted a set of highly conserved residues, in addition to those
      originally noted to occur within WW domains. Substitutions at two of these
      conserved positions completely inhibited ligand binding, whereas substitution at
      a non-conserved position did not. Moreover, mutant WW domains containing
      substitutions at conserved positions bound novel peptide ligands. CONCLUSIONS:
      Class I WW domains contain a highly conserved set of residues that are important
      in selecting Pro-Xxx-Tyr containing peptide ligands. The presence of these
      residues within an uncharacterized WW domain can be used to predict its ability
      to bind Pro-Xxx-Tyr containing peptide ligands.

PMID- 11306349
TI  - A sensitive fluorescence monitor for the detection of activated Ras: total
      chemical synthesis of site-specifically labeled Ras binding domain of c-Raf1
      immobilized on a surface.
AB  - BACKGROUND: The Ras.GDP-Ras.GTP cycle plays a central role in eukaryotic
      signaling cascades. Mutations in Ras which stabilize activated Ras.GTP lead to a
      continuous stimulation of downstream effectors and ultimately to cell
      proliferation. Ras mutants which increase the steady-state concentration of
      Ras.GTP are involved in about 30% of all human cancers. It is therefore of great
      interest to develop a biosensor which is sensitive to Ras.GTP but not to Ras.GDP.
      RESULTS: The Ras binding domain (RBD) of c-Raf1 was synthesized from two
      unprotected peptide segments by native chemical ligation. Two fluorescent amino
      acids with structures based on the nitrobenz-2-oxa-1,3-diazole and coumaryl
      chromophores were incorporated at a site which is close to the RBD/Ras.GTP
      binding surface. Additionally, a C-terminal tag consisting of His6 was
      introduced. The Kd values for binding of the site-specifically modified proteins
      to Ras.GTP are comparable to that of wild-type RBD. Immobilization of C-terminal
      His6 tag-modified fluorescent RBD onto Ni-NTA-coated surfaces allowed the
      detection of Ras.GTP in the 100 nM range. Likewise, Ras.GTP/Q61L (an oncogenic
      mutant of Ras with very low intrinsic GTP hydrolysis activity) can also be
      detected in this assay system. Ras.GDP does not bind to the immobilized RBD, thus
      allowing discrimination between inactive and activated Ras. CONCLUSIONS: The site
      specific incorporation of a fluorescent group at a strategic position in a Ras
      effector protein allows the detection of activated Ras with high sensitivity.
      This example illustrates the fact that the chemical synthesis of proteins or
      protein domains makes it possible to incorporate any kind of natural or unnatural
      amino acid at the position of choice, thereby enabling the facile preparation of
      specific biosensors, enhanced detection systems for drug screening, or the
      synthesis of activated proteins, e.g. phosphorylated proteins involved in
      signaling pathways, as defined molecular species.

PMID- 11306350
TI  - Identification of a sugar flexible glycosyltransferase from Streptomyces
      olivaceus, the producer of the antitumor polyketide elloramycin.
AB  - BACKGROUND: Elloramycin is an anthracycline-like antitumor drug related to
      tetracenomycin C which is produced by Streptomyces olivaceus Tu2353. Structurally
      is a tetracyclic aromatic polyketide derived from the condensation of 10 acetate
      units. Its chromophoric aglycon is glycosylated with a permethylated L-rhamnose
      moiety at the C-8 hydroxy group. Only limited information is available about the
      genes involved in the biosynthesis of elloramycin. From a library of chromosomal
      DNA from S. olivaceus, a cosmid (16F4) was isolated that contains part of the
      elloramycin gene cluster and when expressed in Streptomyces lividans resulted in
      the production of a non-glycosylated intermediate in elloramycin biosynthesis, 8
      demethyl-tetracenomycin C (8-DMTC). RESULTS: The expression of cosmid 16F4 in
      several producers of glycosylated antibiotics has been shown to produce
      tetracenomycin derivatives containing different 6-deoxysugars. Different
      experimental approaches showed that the glycosyltransferase gene involved in
      these glycosylation events was located in 16F4. Using degenerated oligoprimers
      derived from conserved amino acid sequences in glycosyltransferases, the gene
      encoding this sugar flexible glycosyltransferase (elmGT) has been identified.
      After expression of elmGT in Streptomyces albus under the control of the
      erythromycin resistance promoter, ermEp, it was shown that elmG can transfer
      different monosaccharides (both L- and D-sugars) and a disaccharide to 8-DMTC.
      Formation of a diolivosyl derivative in the mithramycin producer Streptomyces
      argillaceus was found to require the cooperative action of two mithramycin
      glycosyltransferases (MtmGI and MtmGII) responsible for the formation of the
      diolivosyl disaccharide, which is then transferred by ElmGT to 8-DMTC.
      CONCLUSIONS: The ElmGT glycosyltransferase from S. olivaceus Tu2353 can transfer
      different sugars into the aglycon 8-DMTC. In addition to its natural sugar
      substrate L-rhamnose, ElmGT can transfer several L- and D-sugars and also a
      diolivosyl disaccharide into the aglycon 8-DMTC. ElmGT is an example of sugar
      flexible glycosyltransferase and can represent an important tool for
      combinatorial biosynthesis.

PMID- 11306351
TI  - Modulating cell surface immunoreactivity by metabolic induction of unnatural
      carbohydrate antigens.
AB  - BACKGROUND: Sialic acid is a component of many tumor-associated oligosaccharide
      antigens. The repertoire of sialic acids presented by cells can be expanded to
      include unnatural variants by intercepting the sialic acid biosynthetic pathway
      with unnatural precursors. We explored whether unnatural cell surface sialosides
      produced by metabolism can act as neo-antigens and modulate the immunogenicity of
      cells. RESULTS: Immunization of rabbits with synthetic conjugates of an unnatural
      sialic acid bound to keyhole limpet hemocyanin produced significant titers of
      antibodies that were specific for the structurally altered sialic acid. The
      antibodies recognized cells that were fed the unnatural biosynthetic precursor,
      and were capable of directing complement-mediated lysis. CONCLUSIONS: Structural
      alteration of sialic acids replaces a tolerized self-antigen with an antigenic
      determinant. Incorporation of unnatural sialosides into cell surface
      glycoconjugates through biosynthetic means can alter the immunoreactivity of
      cells, providing new possibilities for tumor immunotherapy.

PMID- 11306352
TI  - The estrogen receptor: a structure-based approach to the design of new specific
      hormone-receptor combinations.
AB  - BACKGROUND: The specificity of hormone action arises from complementary steric
      and electronic interactions between a hormonal ligand and its cognate receptor.
      An analysis of such key ligand-receptor contact sites, often delineated by
      mutational mapping and X-ray crystallographic studies, can suggest ways in which
      hormone-receptor specificity might be altered. RESULTS: We have altered the
      hormonal specificity of the estrogen receptor alpha (ER) by making 'coordinated'
      changes in the A-ring of the ligand estradiol and in the A-ring binding subpocket
      of ER. These changes were designed to maintain a favorable interaction when both
      E and ER are changed, but to disfavor interaction when only E or ER is changed.
      We have evaluated several of these altered ligand and receptor pairs in
      quantitative ligand binding and reporter gene assays. CONCLUSIONS: In best cases,
      the new interaction is sufficiently favorable and orthogonal so as to represent
      the creation of a new hormone specificity, which might be useful in the
      regulation of transgene activity.

PMID- 11306353
TI  - A small molecule designed to bind to the adenine nucleotide pocket of Hsp90
      causes Her2 degradation and the growth arrest and differentiation of breast
      cancer cells.
AB  - BACKGROUND: The Hsp90s contain a conserved pocket that binds ATP/ADP and plays an
      important role in the regulation of chaperone function. Occupancy of this pocket
      by several natural products (geldanamycin (GM) and radicicol) alters Hsp90
      function and results in the degradation of a subset of proteins (i.e. steroid
      receptors, Her2, Raf). We have used the structural features of this pocket to
      design a small molecule inhibitor of Hsp90. RESULTS: The designed small molecule
      PU3 competes with GM for Hsp90 binding with a relative affinity of 15-20 microM.
      PU3 induces degradation of proteins, including Her2, in a manner similar to GM.
      Furthermore, PU3 inhibits the growth of breast cancer cells causing
      retinoblastoma protein hypophosphorylation, G1 arrest and differentiation.
      CONCLUSIONS: PU3 is representative of a novel class of synthetic compounds that
      binds to Hsp90 and inhibits the proliferation of cancer cells. These reagents
      could provide a new strategy for the treatment of cancers.

PMID- 11306354
TI  - Serum prostate-specific antigen for prostate cancer early detection: total, free,
      age- stratified, or complexed?

PMID- 11306355
TI  - Percent free prostate-specific antigen for first-time prostate biopsy.

PMID- 11306356
TI  - Evaluation of asymptomatic microscopic hematuria in adults: the American
      Urological Association best practice policy--part I: definition, detection,
      prevalence, and etiology.

PMID- 11306357
TI  - Evaluation of asymptomatic microscopic hematuria in adults: the American
      Urological Association best practice policy--part II: patient evaluation,
      cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow
      up.

PMID- 11306358
TI  - Osteoprotegerin and rank ligand expression in prostate cancer.
AB  - OBJECTIVES: To investigate the expression of osteoprotegerin (OPG) and RANK
      ligand (RANKL) in human prostatic tissues. The factors regulating the increased
      turnover associated with prostate cancer (CaP) bone metastasis are unknown. OPG
      and RANKL are recently identified regulators of bone resorption and bone
      remodeling. METHODS: Tissues from 28 patients with CaP and from 4 normal organ
      donors were analyzed by reverse transcriptase-polymerase chain reaction and
      immunohistochemistry for the expression of OPG and RANKL. RESULTS: OPG and RANKL
      messages were detected in both normal and cancerous prostate samples. In the
      normal prostate, OPG protein was detected in luminal epithelial and stromal cells
      (5% to 65% and 15% to 70%, respectively) and RANKL immunoreactivity was observed
      in 15% to 50% of basal epithelial cells, 40% to 90% of luminal epithelial cells,
      and 70% to 100% of stromal cells. OPG was not detected in 8 of 10 primary CaP
      specimens; RANKL was heterogeneously expressed in 10 of 11 CaP specimens. The
      percentage of tumor cells expressing OPG and RANKL was significantly increased in
      all CaP bone metastases compared with nonosseous metastases or primary CaP.
      CONCLUSIONS: CaP bone metastases were consistently immunoreactive for both OPG
      and RANKL compared with nonosseous metastases or primary CaP. The presence of
      these crucial bone resorption regulators in CaP bone metastases suggests a
      mechanism whereby CaP cells may modulate bone turnover and has profound
      implications for the establishment and development of CaP bone metastases in
      advanced disease.

PMID- 11306359
TI  - Leukocyturia as a predictor of tolerance and efficacy of intravesical BCG
      maintenance therapy for superficial bladder cancer.
AB  - OBJECTIVES: To examine leukocyturia as a predictor of tumor recurrence and
      occurrence of adverse events after bacille Calmette-Guerin (BCG) immunotherapy.
      The use of BCG immunotherapy, a very major advance in the management of
      superficial bladder cancer, is limited by the frequency of adverse events. As
      yet, we have no way of predicting the efficacy and tolerability of BCG
      instillation in clinical practice. This problem is even more acute during BCG
      maintenance therapy. METHODS: Adverse events in 72 patients who received 518
      instillations were prospectively assessed using a four-class scale based on
      severity and duration. Urinary leukocytes were counted 3 days after each
      instillation, using the KOVA-Slide 10 method. RESULTS: High leukocyturia during
      BCG treatment (cutoff value 1.65 x 10(5)/mL urine) correlated with recurrence
      free status (P = 0.009). The degree of leukocyturia correlated with the
      severity/duration of adverse events (P <0.0001); the median leukocyturia values
      associated with class I, II, and III adverse events were 4 x 10(4)/mL, 1.5 x
      10(5)/mL, and 3.5 x 10(5)/mL, respectively. No class IV events occurred. The
      cutoff point indicating treatment cessation for adverse events was leukocyturia
      of 8.6 x 10(4)/mL. CONCLUSIONS: These results suggest a link between adverse
      events and efficacy during BCG maintenance therapy. Leukocyturia appears to
      correlate with both efficacy and tolerability in this setting. Prospective
      randomized studies are required to evaluate leukocyturia as a basis on which to
      adapt the BCG instillation schedule to individual patient susceptibility.

PMID- 11306361
TI  - Sildenafil citrate for penile hemodynamic determination: an alternative to
      intracavernosal agents in Doppler ultrasound evaluation of erectile dysfunction.
AB  - OBJECTIVES: To suggest a new noninvasive method for penile Doppler ultrasound
      (PDU) evaluation of erectile dysfunction using oral sildenafil citrate as an
      erection induction agent. METHODS: A total of 20 patients admitted with the
      complaint of erectile dysfunction were evaluated by the short form of the
      International Index of Erectile Function. A total score of less than 25 was
      accepted as erectile dysfunction and PDU was performed. The initial penile study
      consisted of PDU examination under visual sexual stimulation (VSS), and the peak
      systolic velocity, end-diastolic velocity, and resistance index were recorded.
      Measurements of all the parameters were repeated on the same patients after
      intracavernosal papaverine, intracavernosal prostaglandin E(1) (PGE(1)), and oral
      sildenafil citrate administration, plus VSS. All patients had these four tests in
      the same order at weekly intervals. Sildenafil citrate was given orally 45
      minutes before Doppler investigation, and patients had VSS during the waiting
      period. The patients were asked about their satisfaction and comfort after each
      test. Statistical analysis was performed using the Wilcoxon and Mann-Whitney U
      tests. RESULTS: The measurements with papaverine, PGE(1), and sildenafil citrate
      were significantly different from those after only VSS (P <0.008); however, the
      papaverine, PGE(1), and sildenafil citrate results were not different from each
      other according to the peak systolic velocity, end-diastolic velocity, and
      resistance index measurements (P >0.008). Patients commented that although PGE(1)
      was the strongest erectogenic agent, sildenafil citrate was the most convenient.
      CONCLUSIONS: Since the results of PDU with oral sildenafil citrate in association
      with VSS were not statistically different, we suggest a new noninvasive erection
      induction method for the purpose of PDU evaluation of erectile dysfunction.

PMID- 11306365
TI  - Early endoscopic realignment of post-traumatic posterior urethral disruption.
AB  - OBJECTIVES: The management of complete or partial urethral disruption is
      controversial, and much debate continues regarding immediate versus delayed
      definitive therapy. We further analyze our experience and long-term results using
      early endoscopic realignment. METHODS: Between April 1987 and January 1999, 29
      men with posterior urethral disruption (23 complete and 6 partial) underwent
      primary urethral realignment 0 to 8 days after injury. Pelvic fractures were
      present in 23 patients. In all patients, the actual operating time for
      realignment was 75 minutes or less. All patients were evaluated postoperatively
      for incontinence, impotence, and strictures. RESULTS: After a mean follow-up of
      68 months (range 18 to 155), all patients were continent. Four patients (13.7%)
      required conversion to an open perineal urethroplasty. At the last follow-up
      visit, 25 (86%) of the 29 patients were potent and 4 achieved adequate erections
      for intercourse using intracorporeal injections (prostaglandin E(1)). Twelve
      patients (41%) developed short secondary strictures and were successfully treated
      with internal urethrotomy. The mean follow-up of these 12 patients was 83 months
      (range 34 to 120). Urinary flow rate measurement at the last follow-up visit
      revealed satisfactory voiding parameters in all patients. CONCLUSIONS: Primary
      endoscopic realignment offers an effective method for treating traumatic urethral
      injuries. Our long-term follow-up provides additional support for the use of this
      technique by demonstrating that urethral continuity can be established without an
      increased incidence of impotence, stricture formation, or incontinence. In case
      of failure, endoscopic realignment does not compromise the result of secondary
      urethroplasty.

PMID- 11306366
TI  - Primary genitourinary melanoma.
AB  - OBJECTIVES: To describe the presentation, management, and clinical outcome of
      patients with genitourinary melanoma. METHODS: We identified 14 patients with
      genitourinary melanoma treated at Memorial Sloan-Kettering Cancer Center, New
      York and Tripler Army Medical Center, Honolulu, Hawaii. The presentation,
      surgical treatment, disease progression, and outcome of these patients were
      reviewed. Survival was analyzed, using the Kaplan-Meier product limit method.
      RESULTS: The presentation and management of patients with genitourinary melanoma
      were varied. Overall, the prognosis was poor, with a median survival of 43
      months, and only 3 patients were alive, without disease, at last follow-up. Our
      findings confirm a poor prognosis in patients with this rare disease.
      CONCLUSIONS: Genitourinary melanoma is a rare form of the disease with an
      unfavorable clinical outcome. Less than one third of patients survive long term,
      although patients with scrotal melanomas may have a better prognosis.

PMID- 11306367
TI  - Routine placement of ureteral stents is unnecessary after ureteroscopy for
      urinary calculi.
AB  - OBJECTIVES: To report a matched comparison of patients with and without stenting
      after ureteroscopy for calculi, including middle or proximal ureteral and renal
      calculi. The elimination of routine stenting after ureteroscopy would prevent
      stent pain, minimize the need for re-instrumentation, and reduce costs-as long as
      efficacy and safety are not diminished. METHODS: Of 318 patients who underwent
      ureteroscopy, 81 (25%) did not have a ureteral stent placed. Of those, 51 were
      suitable for analysis and included patients with distal ureteral (n = 22), middle
      or proximal ureteral (n = 11), and renal calculi (n = 18). This cohort was
      matched to a stented group by stone size and location. RESULTS: The preoperative
      characteristics of the groups were similar. A stone-free rate of 86% and 94% was
      achieved in the stented and nonstented groups, respectively (P = 0.32).
      Complications in the nonstented group were less frequent (flank pain in 3 and
      postoperative nausea in 1) than in the stented group (hospital visits for flank
      pain in 12, persistent nausea and vomiting in 1, sepsis in 1, perinephric
      hematoma in 1, and urinary retention in 1) (total of 4 versus 16, P = 0.025).
      CONCLUSIONS: Ureteroscopy for distal ureteral stones without ureteral stent
      placement has been previously described. Our experience expands to include the
      elimination of stent placement after ureteroscopy for middle or proximal ureteral
      (22%) and renal (35%) calculi. Our data suggest that after ureteroscopies with
      short operative times and minimal ureteral trauma, ureteral stents may not be
      necessary, even if proximal ureteral or renal ureteroscopy has been performed.

PMID- 11306369
TI  - Retroperitoneoscopic nephrectomy and nephroureterectomy for benign nonfunctioning
      kidneys: a single-center experience.
AB  - OBJECTIVES: To report our experience of 185 cases of retroperitoneoscopic
      nephrectomy and nephroureterectomy for benign nonfunctioning kidneys with various
      modified techniques for differing etiologies. The feasibility, complications, and
      long-term outcomes are discussed. METHODS: The present study comprised 185
      patients who underwent retroperitoneoscopic nephrectomy or nephroureterectomy
      during a 57-month period beginning July 1995. All procedures were done using the
      retroperitoneoscopic approach. Thirty-two patients had a history of previous
      surgery, 20 patients had a percutaneous nephrostomy, and 12 patients had mild
      renal impairment. RESULTS: Retroperitoneoscopic nephrectomy and
      nephroureterectomy were completed successfully in 167 patients. Eighteen patients
      required conversion to open surgery, 4 on an emergent basis and 14 electively.
      The mean operating time was 100 minutes (range 45 to 240), mean blood loss was
      133 mL (range 30 to 1200), and mean hospital stay was 3 days (range 2 to 8). A
      total of 37 complications (16.2% were minor and 3.78% were major) occurred. Re
      intervention was needed in 1 patient. No mortality resulted. Previous surgery,
      percutaneous nephrostomy, and chronic renal impairment did not affect the
      outcome. Apart from one incisional hernia, no long-term complications occurred.
      CONCLUSIONS: Retroperitoneoscopic nephrectomy and nephroureterectomy can be
      performed safely and successfully with obvious advantages for benign
      nonfunctioning kidneys regardless of the etiology or pathogenesis, with
      modifications in the approach in very difficult cases. Patients with conditions
      often considered to be contraindications (ie, genitourinary tuberculosis,
      pyonephrosis, history of previous surgery, percutaneous nephrostomy, stone
      disease, chronic renal failure, and horseshoe kidney) can also be successfully
      treated by skillful dissection and modifications in the surgical technique.

PMID- 11306370
TI  - Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in
      advanced renal cell carcinoma: a phase II study.
AB  - OBJECTIVES: Chemotherapy resistance of renal cell carcinoma (RCC) has been
      attributed in large part to multidrug resistance (MDR). Reported MDR-modulated
      chemotherapy for RCC, however, has resulted in only marginal response benefits.
      In this study, the MDR-modulated effect of paired tamoxifen and colchicine on
      vinblastine and the possible additive effect of 5-fluorouracil (5-FU) were
      investigated in the treatment of advanced RCC. METHODS: Chemotherapy was
      administered every 4 weeks with biweekly vinblastine (4 mg/m(2)/day,
      intravenously on days 1 and 15) modulated by oral tamoxifen (100 mg/day) and
      colchicine (1 mg/day) from days -1 to 2 and from days 13 to 16. 5-FU (800
      mg/m(2)/day from days 2 to 5) was administered after vinblastine administration
      as a continuous infusion. RESULTS: Of 17 eligible patients with advanced RCC
      available for evaluation, 1 achieved a complete response (CR) and 3 a partial
      response (PR), with an overall response (CR plus PR) rate of 23.5%. The median
      overall survival time of all patients was 10 months (95% confidence interval [CI]
      3.5 to 16.5); that of our patients with poor, intermediate, and favorable risks
      as stratified by Motzer's model was 6 (95% CI 1.7 to 10.3), 10 (95% CI 7.9 to
      12.2), and 26 (95% CI 24.4 to 27.6) months, respectively. These results are
      encouraging in view of the poor efficacy of chemotherapy in RCC observed
      previously. Additionally, the treatment toxicity was limited: toxicity of grade 3
      or greater occurred in only 1 patient with leukopenia, and no treatment-related
      mortality was found. CONCLUSIONS: The encouraging response rates and overall
      survival with limited toxicity warrant further investigation of this combination
      therapy as an integrated part of immunochemotherapy for RCC.

PMID- 11306371
TI  - Can the sensory threshold toward electrical stimulation be used to quantify the
      subjective perception of bladder filling? A study in young healthy volunteers.
AB  - OBJECTIVES: To evaluate whether electrosensation can be used as a quantitative
      measurement for the sensations felt during bladder distension. METHODS: A total
      of 48 healthy volunteers were examined. Sensations of bladder distension were
      evaluated during medium-fill cystometry. Electrosensation was quantified by
      obtaining electrical thresholds at different sites in the lower urinary tract
      with constant current stimulation at 2.5 and 95 Hz. RESULTS: Both currents were
      perceived differently. Thresholds at 95 Hz were significantly higher than at 2.5
      Hz for each location. With neither current could a significant correlation be
      found between the parameters of filling perception and electrosensation in the
      lower urinary tract. CONCLUSIONS: Although the use of electrical thresholds is a
      valuable technique in the diagnosis of neuropathic disorders in the lower urinary
      tract, at the current settings it cannot be used to quantify the perception of
      bladder filling.

PMID- 11306374
TI  - Endoluminal magnetic resonance imaging in the evaluation of urethral diverticula
      in women.
AB  - OBJECTIVES: Accurate determination of the size and extent of urethral diverticula
      can be important in planning operative reconstruction and repair. Voiding
      cystourethrography (VCUG) is currently the most commonly used study in the
      preoperative evaluation of urethral diverticula. We reviewed our experience with
      the use of endoluminal (endorectal or endovaginal) magnetic resonance imaging
      (eMRI) in these patients as an adjunctive study to VCUG to evaluate whether the
      MRI provided anatomically important information that was not apparent on VCUG.
      METHODS: A retrospective analysis of all patients with a clinical diagnosis of
      urethral diverticula undergoing MRI at a single institution was performed.
      Patients were evaluated with history, physical examination, cystoscopy, VCUG, and
      eMRI. Endoluminal MRI was retrospectively compared to VCUG with respect to size,
      extent, and location found at operative exploration. RESULTS: Twenty-seven
      consecutive patients underwent endorectal or endovaginal coil MRI in the
      evaluation of suspected urethral diverticula. Twenty patients subsequently had
      attempted transvaginal operative repair of the diverticulum. In 2 patients, eMRI
      demonstrated a urethral diverticulum, whereas VCUG did not. Operative exploration
      in these patients revealed a urethral diverticulum. In 14 of 27 patients, the
      VCUG underestimated the size and complexity of the urethral diverticulum as
      compared to eMRI and operative exploration. In 13 of 27 patients, the size,
      location, and extent of the urethral diverticulum on VCUG correlated well with
      the eMRI and/or operative findings. CONCLUSIONS: We have found endorectal and
      endovaginal coil MRI to be extremely accurate in determining the size and extent
      of urethral diverticula as compared to VCUG. This information can be critical
      when planning the approach, dissection, and reconstruction of these sometimes
      complex cases.

PMID- 11306375
TI  - Transvaginal sacrospinous colpopexy by palpation-a new minimally invasive
      procedure using an anchoring system.
AB  - OBJECTIVES: To evaluate the preliminary results and complications of a new,
      minimally invasive, transvaginal sacrospinous colpopexy for vault and
      uterovaginal prolapse. METHODS: Twelve women, 41 to 79 years old, underwent
      sacrospinous fixation by palpation using the Raz Anchoring System (RAS) between
      October 1998 and September 1999. The vaginal vault prolapse was grade II and III
      in 4 and 6 patients, respectively. Two patients had grade III uterovaginal
      prolapse. Two patients underwent RAS alone, and 10 underwent RAS in conjunction
      with simultaneous related vaginal surgery. Eleven patients underwent vaginal
      vault and one uterovaginal fixation. RAS features two components: first, a 15-mm
      long cylindrical titanium anchor and second, a disposable inserter. A penetration
      limiter tube allows one to penetrate the sacrospinous ligament up to the desired
      depth. The anchor is released into the ligament and then the vaginal apex is
      fixed in place. RESULTS: The minimum and mean follow-up was 12 and 16 months,
      respectively. The operative time to complete the colpopexy ranged from 8 to 15
      minutes. We recorded only one recurrent vaginal vault prolapse due to pull
      through of the suspension sutures through the vagina. No significant
      perioperative complications occurred. No de novo or recurrent cystocele,
      rectocele, enterocele, stress urinary incontinence, urgency, or frequency was
      seen. Defecation was normal in all patients. Coital function was normal in 8
      patients who were still sexually active. No patient experienced perineal or
      buttock pain. CONCLUSIONS: RAS seems to be quick, easy, safe, and effective in
      the suspension of vaginal apex to the sacrospinous ligament, but our preliminary
      results must be confirmed by controlled prospective studies with a larger number
      of patients and wider follow-up.

PMID- 11306377
TI  - Interposition flaps in transabdominal vesicovaginal fistula repairs: are they
      really necessary?
AB  - Objectives. To evaluate the use of interposition flaps in repairing vesicovaginal
      fistulas (VVFs) of benign and malignant etiologies. Interposition flaps are not
      routinely used in the repair of VVFs when the surrounding tissues appear healthy
      and well-vascularized, such as in a benign etiology.Methods. We retrospectively
      reviewed the charts of 37 women (mean age 49.1 years) at our institution who
      underwent transabdominal repair of their VVF by urologic surgeons between August
      1978 and June 1999. The preoperative and postoperative medical records were
      reviewed.Results. Of the 37 VVFs repaired transabdominally, 29 had a benign
      etiology (25 related to gynecologic procedures) and 8 a malignant etiology (all
      related to gynecologic neoplasia). Of the 29 benign VVFs, an interposition flap
      was used in 10 repairs with all 10 successful (100%). The remaining 19 benign VVF
      repairs were performed without using a flap, with 12 successful (63%). Of the 8
      malignant fistulas, an interposition flap was used in 2 repairs with both
      successful (100%). The remaining 6 malignant VVF repairs were performed without a
      flap, with 4 successful (67%).Conclusions. The results of our study indicate a
      higher success rate for transabdominal VVF repairs performed with an
      interposition flap (100% success rate at our institution). This observation holds
      true regardless of the appearance of healthy surrounding tissue or, more
      importantly, a benign or malignant etiology. We recommend interposition flaps in
      transabdominal repairs of VVFs, even in the cases of benign fistulas with well
      preserved surrounding tissue.

PMID- 11306379
TI  - Excretion of matrix metalloproteinases 2 and 9 in urine is associated with a high
      stage and grade of bladder carcinoma.
AB  - OBJECTIVES: To analyze the excretion of matrix metalloproteinases (MMPs) 2 and 9
      in the urine of patients with bladder cancer according to the stage and grade of
      tumor and to evaluate their diagnostic clinical validity. In numerous carcinomas,
      increased expression of MMPs is associated with a higher grade of malignancy and
      poor prognosis. METHODS: The study population included 44 controls without
      evidence of malignancy, 14 patients with cystitis, and 43 patients with Stage Ta
      T1, 18 patients with Stage T2, and 10 patients with Stage T3-T4 bladder cancer.
      MMP-2 and MMP-9 excretion in urine samples was measured with gelatin zymography
      and related to the urine creatinine concentration. The evaluation of data was
      performed by univariate statistical analysis, logistic regression analysis, and
      receiver operating characteristic analysis. RESULTS: The upper cutoff limit for
      MMP-2 and MMP-9 excretion was 277 microg/g creatinine and 648 microg/g
      creatinine, respectively. Levels of MMP-2 and MMP-9 correlated with each other
      and with tumor stage and grade. Elevated excretions were mainly observed in
      patients with invasive tumors (Stage T2-T4). In the receiver operating
      characteristic analysis, the areas under the curves for MMP-2 and MMP-9 were
      significantly higher in patients with muscle-invasive than in patients with
      noninvasive tumors. Related to the cutoff limits, the overall sensitivity to
      detect bladder cancer was 0.51 for MMP-2 and 0.31 for MMP-9. In logistic
      regression analysis, MMP-2 showed the best results. CONCLUSIONS: Urinary
      excretion of MMP-2 and MMP-9 is associated with a high stage and grade of bladder
      cancer, and they may serve as indicators of tumor progression and recurrence in
      the future.

PMID- 11306380
TI  - Analysis of false-positive BTA STAT test results in patients followed up for
      bladder cancer.
AB  - OBJECTIVES: To evaluate the role of a positive BTA stat Test result in patients
      with negative cystoscopic findings. METHODS: Five hundred one consecutive
      patients in follow-up for bladder cancer were studied. A voided urine sample was
      obtained before cystoscopy and split for culture, cytology, and BTA stat testing.
      In the case of a positive BTA stat Test, but negative cystoscopic findings,
      patients underwent additional investigations. RESULTS: Of 501 patients, 133
      (26.5%) had bladder cancer recurrence at cystoscopy, of which the BTA stat Test
      detected 71 (53.4%); only 21 of the cases (17.9%) were detected by cytologic
      examination. Of the remaining 368 patients with no visible tumor at cystoscopy,
      96 (26.1%) had a positive BTA stat Test result. Fifty-five of those (57.3%)
      underwent intravenous urography or renal ultrasound and random biopsies, and an
      additional 9 recurrences (16.4%) were detected. Of those 46 patients who had a
      true false-positive BTA stat Test, 3 (3 of 43, 7.0%) had recurrence at the next
      follow-up cystoscopy, 4 (8.7%) had a urine infection, and 8 (17.4%) had ongoing
      intravesical instillations; the latter two percentages were significantly higher
      than among those with true-negative BTA stat Test results (0% and 6.8%,
      respectively). CONCLUSIONS: Patients with a positive BTA stat Test result but
      negative cystoscopic findings have about a 16% risk of an undetected recurrence.
      False-positive results may be due to present instillation treatment and urine
      infection, and the predictive value of a BTA stat Test for subsequent recurrence
      seems relatively low.

PMID- 11306381
TI  - Usefulness of the BTA STAT Test for the diagnosis of bladder cancer.
AB  - OBJECTIVES: To evaluate the usefulness of the Bard BTA stat Test in the diagnosis
      and follow-up of bladder cancer and to compare this test to cytologic analysis
      and cystoscopy, routine diagnostic methods. METHODS: Three hundred seventy-nine
      patients being followed up because of bladder cancer or with symptoms suggestive
      of bladder cancer underwent cystoscopy, cytologic analysis, and the BTA stat Test
      using a recently voided urine sample. In suspected cases, transurethral resection
      and histopathologic analysis were performed. RESULTS: Of the 379 patients, 235
      proved to have bladder cancer and 144 did not. The sensitivity was 73.62% for the
      BTA stat, 61.70% for cytologic examination, and 99.57% for cystoscopy. The
      specificity was 83.33% for the BTA stat, 92.36% for cytologic analysis, and
      85.42% for cystoscopy. The BTA stat Test's sensitivity for grades 1, 2, and 3
      tumor was 47.27%, 69.15%, and 95.35%, respectively. The sensitivity of cytologic
      analysis was 30.91%, 55.32%, and 88.37%. The BTA stat Test's sensitivity for
      stage was 45.65% in Stage Ta, 75.52% in T1, and 95.56% in Stage T2-4; the
      cytologic results were 28.26%, 65.03%, and 84.44%, respectively. The combination
      of both tests improved the sensitivity and decreased the specificity slightly.
      CONCLUSIONS: The high sensitivity of the BTA stat Test, together with the data
      obtained from the parameters used for the evaluation of the test, demonstrate the
      better results of the BTA stat Test compared with cytologic analysis, making it a
      thoroughly valid diagnostic tool in the diagnosis of bladder cancer. In our
      opinion, the BTA stat Test can replace the use of cytologic analysis in the
      diagnosis of bladder cancer, but not the use of cystoscopy.

PMID- 11306382
TI  - Endoscopic detection of transitional cell carcinoma with 5-aminolevulinic acid:
      results of 1012 fluorescence endoscopies.
AB  - OBJECTIVES: The initial encouraging results using 5-aminolevulinic acid (5-ALA)
      induced fluorescence endoscopy (AFE) have promised a procedure with an
      outstanding sensitivity for the detection of early stage bladder cancer.
      Summarized here is our clinical experience and data comprising 1012 fluorescence
      endoscopies. METHODS: Two hours, 30 minutes before endoscopy, 1.5 g 5-ALA
      dissolved in 50 mL of 5.7% sodium monohydrogen phosphate was instilled in
      patients intravesically. Before AFE, all patients underwent white light
      endoscopy, and a bladder washing cytologic specimen was obtained. A special light
      source provided blue light (375 to 440 nm) for fluorescence excitation.
      Suspicious sites were identified by their red fluorescence contrasting against
      backscattered blue light when observed through the long pass filter (445 nm)
      integrated into the telescope eyepiece. RESULTS: Two thousand four hundred
      seventy-five specimens were obtained (2.4 biopsies per AFE). In 552 AFEs (54.5%),
      neoplastic urothelial lesions were detected, in 34.2% only because of their
      positive fluorescence; 38.7% of these additionally detected neoplastic foci had
      poorly differentiated histologic features. CONCLUSIONS: AFE has proved to be a
      clinically feasible procedure with an outstanding detection rate for flat,
      urothelial, high-risk lesions.

PMID- 11306383
TI  - Symptoms and quality of life versus age, prostate volume, and urodynamic
      parameters in 565 strictly selected men with lower urinary tract symptoms
      suggestive of benign prostatic hyperplasia.
AB  - OBJECTIVES: To investigate the associations of symptoms and quality of life with
      age, prostate volume, and urodynamic parameters in a large group of strictly
      selected men with lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia. METHODS: The 565 consecutive men met all the criteria of the
      International Consensus Committee on benign prostatic hyperplasia and voided more
      than 150 mL during uroflowmetry. The residual volumes and prostate sizes were
      estimated. The International Prostate Symptom Score (IPSS) and quality-of-life
      score were collected and urodynamic evaluations performed. RESULTS: The prostate
      volume and obstruction grade were not, but low detrusor contractility and low
      bladder capacity were, significantly associated with symptoms. Except for
      nocturia, older men presented with lower voiding scores on the IPSS. The presence
      of a residual urine volume hardly influenced patients' symptoms and quality of
      life. Men with an unstable bladder scored higher on frequency, urgency, and
      nocturia on the IPSS, but the symptom index and quality-of-life score were not
      affected by the presence of an unstable bladder. Because of the high variability
      and subjective interpretation of symptoms and because urodynamic parameters may
      have opposite implications than symptoms and vice versa, associations were still
      weak. CONCLUSIONS: Except for nocturia, older men had lower voiding scores on the
      IPSS. Prostate volume and obstruction grade were not, but low detrusor
      contractility and low capacities were, associated with the symptom index. The
      presence of an unstable bladder and/or residual volume was hardly associated with
      the symptom index or quality-of-life score. Although we used a large group of
      strictly selected men, the associations were still weak.

PMID- 11306384
TI  - Microwave thermotherapy for benign prostatic hyperplasia with the Dornier
      Urowave: response durability and variables potentially predicting response.
AB  - OBJECTIVES: To evaluate the clinical efficacy and durability of transurethral
      microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia.
      The clinical variables useful in predicting outcome were identified. METHODS:
      From October 1996 to March 2000, 58 patients with symptomatic benign prostatic
      hyperplasia were treated with TUMT using the Urowave device. Treatment outcome
      was evaluated by the International Prostate Symptom Score (IPSS), quality-of-life
      assessment score, and urodynamic investigation. The patients were divided into
      those having a good and poor response on the basis of the degree of IPSS decrease
      at 3 months. RESULTS: The mean IPSS significantly decreased from 19.2 at baseline
      to 13.3 at 3 months (P <0.0001). The mean quality-of-life score changed from 4.6
      at baseline to 2.9 at 3 months (P <0.0001). No statistically significant
      differences in peak flow rate, postvoid residual volume, Schafer's obstruction
      scale, or detrusor pressure at peak flow were noted before or after TUMT. The
      pretreatment IPSS of the good response group was significantly higher than that
      of the poor response group (P=0.017). A more significant difference was obtained
      for the obstructive score (P = 0.002), and no difference was observed in the
      irritative score (P = 0.631). The Schafer grading scale score of the good
      response group was significantly smaller than that of the poor response group (P
      = 0.047). CONCLUSIONS: TUMT with the Urowave was effective in eliminating
      symptoms associated with benign prostatic hyperplasia, but did not markedly
      improve the objective voiding parameters. Patients with urodynamically less
      obstructive symptoms but subjectively more obstructive symptoms are therefore
      probably good candidates for TUMT.

PMID- 11306387
TI  - Serum acid phosphatase level and biochemical recurrence following radical
      prostatectomy for men with clinically localized prostate cancer.
AB  - OBJECTIVES: Serum acid phosphatase (ACP) was once used as the marker for advanced
      prostate cancer. However, with the development of assays for prostate-specific
      antigen (PSA), a more sensitive and specific tumor marker, the use of ACP has
      diminished. We investigated the prognostic value of preoperative serum ACP in
      predicting prognosis for men with localized prostate cancer following radical
      retropubic prostatectomy (RRP). METHODS: Of 2293 men treated from 1982 to 1998,
      1681 men had a preoperative ACP measurement using an enzymatic assay. We analyzed
      the actuarial freedom from biochemical (PSA) progression following RRP according
      to ACP levels. We used multivariate logistic regression and proportional hazards
      models to determine the independent prognostic value of ACP level with respect of
      pathologic stage and biochemical recurrence. RESULTS: ACP was not an independent
      predictor of organ confinement or lymph node involvement in the multivariate
      logistic regression models using preoperative variables. However, in the
      proportional hazards model, ACP was an independent predictor of tumor recurrence
      following RRP, and there was a statistically significant improvement in
      biochemical recurrence-free survival for men with lower levels of ACP (P <0.001).
      Furthermore, the normalized hazard ratios of ACP and PSA for predicting
      biochemical recurrence were similar. CONCLUSIONS: Stratification of men according
      to their preoperative ACP levels was predictive of patient outcome after RRP.
      Proportional hazards modeling using preoperative variables demonstrated that the
      serum ACP level is an independent predictor of tumor recurrence following RRP.

PMID- 11306388
TI  - Evaluation of a low-invasive strategy for prostate cancer screening with prostate
      specific antigen.
AB  - OBJECTIVES: To evaluate a two-step strategy for the detection of prostate cancer
      within the context of serial screening and compare this strategy with other
      screening strategies. The optimal combination of tests proposed for prostate
      cancer screening remains undetermined, particularly when screening is repeated
      over time. METHODS: A prospective serial prostate cancer screening study with
      follow-up to 55 months was performed in a general community screening clinic. One
      thousand seven hundred seven self-referred men, 50 to 75 years old, without a
      history of prostate cancer agreed to undergo screening for prostate cancer on an
      annual basis. Serum prostate-specific antigen (PSA) measurement was the first
      step screening test. If the serum PSA test was positive, a standard urologic
      evaluation was performed. Biopsy was recommended only if a test other than serum
      PSA was suspicious for cancer. The outcome measures were the biopsy rate and
      prostate cancer detection rate. The comparisons with other studies were age
      standardized to correct for differences in age distribution. RESULTS: The biopsy
      and cancer detection rates after the first test were 7.0% and 2.0%, respectively.
      After 4 years of the study, the cumulative biopsy rate and cumulative cancer
      detection rate per enrolled man was 12% and 4.1%, respectively. The comparisons
      between studies revealed that screening strategies using serum PSA as a first
      line test had similar detection rates but lower biopsy rates than strategies
      performing biopsy when one of several screening tests was positive. CONCLUSIONS:
      A two-step screening strategy using serum PSA alone as the initial test seemed
      able to detect as many cancers as when all screening tests were used at the same
      time but reduced the number of unnecessary biopsies.

PMID- 11306389
TI  - Prostate-specific antigen in female urine: a prospective study involving 217
      women.
AB  - OBJECTIVES: Histomorphologic studies have provided evidence of prostate-specific
      antigen (PSA)-producing tissue in the female urethra. Some urine samples from
      women in a small series were positive for PSA, but no systematic investigation of
      this subject has been done to date. METHODS: In a prospective study, we analyzed
      whether PSA occurs in the urine of women and what factors induce detectable PSA
      levels. The urine samples of 217 women were analyzed (Hybritech-Tandem E-PSA)
      under standardized conditions. The impact of urine pH and volume was
      investigated, and the results were correlated with clinical data (age, residual
      urine, urinary tract infection and prior sexual intercourse within 48 hours).
      RESULTS: A positive PSA level greater than the detection limit of 0.1 ng/mL was
      found in 11% of the analyzed samples; their mean value was 0.29 ng/mL. pH
      correction did not result in a significant difference. The voiding volume had no
      influence on the PSA level. Among the cases of detectable PSA, women younger than
      50 years of age (n = 14) had a mean PSA of 0.34 ng/mL and those older than 50
      years (n = 9) a mean of 0.23 ng/mL. One of 9 women with and 22 of 208 women
      without residual urine volume had a detectable PSA level, as did 0 of 20 with and
      23 of 197 women without urinary tract infection, and 3 of 7 with and 20 of 210
      women without prior sexual intercourse within the previous 48 hours. None of the
      differences were significant. CONCLUSIONS: A urine PSA level was detected in 11%
      of all women studied, with PSA values apparently age dependent. Any urine portion
      is suitable for analysis. No influence was determined for residual urine volume
      or urinary tract infection. Sexual intercourse may cause detectable PSA values,
      but the data of this study did not provide sufficient evidence for this
      hypothesis.

PMID- 11306390
TI  - Dynamic endorectal magnetic resonance imaging for local staging and detection of
      neurovascular bundle involvement of prostate cancer: correlation with
      histopathologic results.
AB  - OBJECTIVES: To assess the staging accuracy and detection of neurovascular bundle
      involvement by dynamic subtraction contrast-enhanced endorectal magnetic
      resonance imaging (MRI) in patients with localized prostate cancer. METHODS: In
      38 patients with biopsy-proven prostate cancer, endorectal MRI was performed on a
      1.5-Tesla magnetic resonance system using the dynamic technique with gadolinium
      diethylenetriaminepentaacetic acid bolus enhancement. Two radiologists
      prospectively assessed the tumor involvement, localization, capsular penetration,
      seminal vesicle invasion, and neurovascular bundle involvement. All patients
      subsequently underwent radical prostatectomy, and the MRI findings were
      correlated with the histopathologic results. RESULTS: The overall accuracy of
      detecting cancer localization in the prostate was 72%. The detection of
      involvement in the peripheral zone had an 80% accuracy rate, but for lesions in
      the transition zone, the rate was 63%. The sensitivity and specificity of tumor
      detection was 81% and 79% for peripheral zone cancers and 37% and 97% for
      transition zone cancers, respectively. The accuracy rate, was 84%, 97%, and 97%
      for the detection of capsular penetration, seminal vesicle invasion, and
      neurovascular bundle involvement, respectively. CONCLUSIONS: Prostatic MRI with
      an endorectal surface coil using the dynamic technique more accurately detected
      tumor localization, capsular penetration, seminal vesicle invasion, and
      neurovascular bundle involvement than previously reported methods. The detection
      of tumor localization was more accurate in the peripheral zone than in the
      transition zone. This technique may be useful for the selection of patients for
      radical prostatectomy and, particularly, for identifying candidates for nerve
      sparing surgery.

PMID- 11306391
TI  - Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate
      cancer: a systematic review.
AB  - OBJECTIVES: Combined androgen blockade with medical or surgical castration plus a
      nonsteroidal antiandrogen for metastatic prostate cancer has been the subject of
      20 randomized trials. The findings range from no expected increase in survival in
      17 studies to an estimated 3.7 to 7 months' survival improvement noted in 3
      studies. Most recently, a 1999 evidence report from the Agency for Healthcare
      Research and Quality and a 2000 overview from the Prostate Cancer Trialists
      Collaborative Group indicated that combined androgen blockade was associated with
      an approximately 3% to 5% increase in 5-year survival. We report herein a
      systematic review on combined androgen blockade performed by the Cochrane
      Collaborative Review Group on Prostate Diseases. METHODS: Controlled trials that
      included a randomization of immediate nonsteroidal antiandrogens with castration
      versus castration alone for metastatic prostate cancer and provided information
      on survival were reviewed. Information on overall survival, toxicity, progression
      free survival, cancer-specific survival, and type of nonsteroidal antiandrogen
      and castration therapies was abstracted by two independent reviewers. RESULTS:
      Twenty trials (n = 6320 patients) were included. The pooled odds ratio (OR) for
      overall survival with combined androgen blockade was 1.03 (95% confidence
      interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95% CI 1.00 to 1.33;
      n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials)
      at 1, 2, and 5 years, respectively. Progression-free survival was improved at 1
      year (OR = 1.38; 95% CI 1.15 to 1.67; n = 2278 from 7 trials). Cancer-specific
      survival was improved at 5 years (OR = 1.58; 95% CI 1.05 to 2.37; n = 781 from 2
      trials). When analysis was limited to studies identified as being of high
      quality, the pooled OR for overall survival progressively increased but was not
      significant at any follow-up interval. CONCLUSIONS: We find that there is a 5%
      improvement in the percentage of men surviving at 5 years (30% vs. 25%) with
      combined androgen blockade with nonsteroidal antiandrogens as well as
      improvements in progression-free survival at 1 year. Appropriate patients with
      metastatic prostate cancer should be informed of the potential benefits,
      toxicities, and out-of-pocket expenditures.

PMID- 11306392
TI  - Disappearance of well-differentiated carcinoma of the prostate: effect of
      transurethral resection of the prostate, prostate-specific antigen, and prostate
      biopsy.
AB  - OBJECTIVES: To characterize the effect of prostate-specific antigen (PSA) and
      transurethral resection of the prostate (TURP) on the rate of diagnosis of well
      differentiated (WD) prostate cancer (PCa) and PCa mortality. METHODS: All cases
      of PCa and rates of TURP at both Wilford Hall and Brooke Army Medical Centers
      between 1984 and 1995 were reviewed. Tumor grade was compared between prostate
      needle biopsy and TURP. The pattern of diagnosis was analyzed annually and for
      two time periods: pre-PSA (1984 to 1988) and post-PSA (1989 to 1995). RESULTS:
      The number of WD tumors fell by 50% over the period of study and was caused by a
      fall in number of TURPs as well as in WD tumors detected by TURP. PSA for early
      detection of PCa began in 1988, and within 5 years a more than 50% fall in the
      rate of metastatic disease was witnessed. These two events (PSA screening and
      fall in TURPs) led to an increase from 57% to 92% of tumors that were both
      clinically significant and potentially curable. CONCLUSIONS: These data help
      explain the fall in the rate of diagnosis of WD PCa. The resultant increase in
      the diagnosis of moderately and poorly differentiated PCa, coupled with the
      dramatic fall in the rate of diagnosis of metastatic PCa, may explain the reports
      of a fall in PCa mortality. If this observation is replicated in other
      populations, it may provide further impetus for a stronger recommendation for
      early detection with PSA and digital rectal examination.

PMID- 11306393
TI  - Comparison of two different doses of preoperative recombinant erythropoietin in
      men undergoing radical retropubic prostatectomy.
AB  - OBJECTIVES: To determine whether the response to recombinant erythropoietin is
      dose dependent in men undergoing radical prostatectomy and to elucidate the
      relative cost-effectiveness of two dosing regimens. METHODS: A prospective, open
      label study comparing the effectiveness, cost, and safety of two different doses
      of recombinant erythropoietin was performed in men undergoing radical retropubic
      prostatectomy. The first 100 men received 600 IU/kg (high dose) of epoetin alfa.
      A second group of 100 men received 300 IU/kg (low dose). All men received two
      doses of erythropoietin on preoperative days 14 and 7, provided their baseline
      hematocrit levels were less than 48%. Hematocrit levels were measured at baseline
      (more than 14 days before surgery), at the time of anesthesia induction, in the
      recovery room postoperatively, on the first postoperative day, and on the morning
      of discharge. RESULTS: The mean increase in hematocrit from baseline to induction
      for the high and low-dose groups was 4.50 and 4.69, respectively (P = 0.7225).
      Six men (6%) in the high-dose group and seven (7%) in the low-dose group required
      allogenic blood transfusions. The mean cost of high and low-dose epoetin alfa was
      $1218 and $656, respectively. The cost per percentage point increase in
      hematocrit in the low-dose group was significantly less than in the high-dose
      group. No thromboembolic events occurred in the high or low-dose group.
      CONCLUSIONS: In men undergoing radical retropubic prostatectomy, the
      administration of epoetin alfa on preoperative days 14 and 7 was a safe and
      effective treatment strategy for reducing the risk of allogenic blood
      transfusions. The 300 IU/kg dosing regimen was significantly more cost effective
      than the 600 IU/kg dosing regimen.

PMID- 11306394
TI  - Anastomotic strictures following radical prostatectomy: insights into incidence,
      effectiveness of intervention, effect on continence, and factors predisposing to
      occurrence.
AB  - OBJECTIVES: To examine the incidence, effectiveness of intervention, effect on
      continence, and factors predisposing to the occurrence of anastomotic strictures
      following radical retropubic prostatectomy. METHODS: Between January 1994 and
      June 1999, 753 radical retropubic prostatectomies were performed by a single
      surgeon. Anastomotic strictures were managed by dilatation followed by a self
      catheterization regimen. Dilatations were repeated unless more than three
      dilatations were required over a 9-month interval. A control group representing a
      randomly selected group of men who did not develop anastomotic strictures was
      identified. The largest width of the midline vertical abdominal scar was
      measured. RESULTS: Of the 753 radical retropubic prostatectomies, 36 (4.8%)
      developed an anastomotic stricture. The mean time interval between the surgical
      procedure and diagnosis of the stricture was 4.22 months. Of the 26 cases of
      anastomotic strictures with at least 1-year follow-up, 24 (92.3%) were managed
      successfully by dilatations alone. No baseline characteristics before surgery
      were associated with the development of a stricture. The maximal scar width was
      the only factor that was associated with the development of a stricture in this
      study. Men with a maximal scar of greater than 10 mm were eight times more likely
      to develop strictures than men with smaller scars. The percentage of men who
      required protective pads 1 year following radical retropubic prostatectomy in the
      control and stricture groups was 12.5% and 46.2%, respectively. CONCLUSIONS:
      Anastomotic strictures are relatively rare following radical prostatectomy and
      have a negative effect on the development of continence. Most men are
      successfully managed with dilatations alone. The development of anastomotic
      strictures in some men appears to be related to a generalized hypertrophic wound
      healing mechanism.

PMID- 11306395
TI  - Cancer incidence in relatives of patients with testicular cancer in the eastern
      part of The Netherlands.
AB  - OBJECTIVES: To investigate the incidence of malignant tumors in first-degree
      relatives of patients with testicular cancer. METHODS: Information about the
      occurrence of cancer in relatives of patients treated for testicular germ cell
      cancer (TC) at the Department of Urology of the University Medical Centre
      Nijmegen from 1986 to 1997 was collected using postal questionnaires from 379
      (72%) of 524 patients. The expected numbers of cancers in relatives were computed
      from age- and sex-specific incidence data in the Netherlands Cancer Registry. The
      observed/expected (O/E) ratios with 95% confidence intervals (CIs) were
      calculated using Byar's approximation of the exact Poisson test. RESULTS: The O/E
      ratio for developing cancer in the families of patients with TC was 1.2 (95% CI
      1.0 to 1.3). Among first-degree relatives of patients with TC, more TC was
      observed than expected (O/E 3.3; 95% CI 1.4 to 6.9). The risk for brothers of
      patients with TC increased 5.9-fold (95% CI 2.2 to 12.8). Both the risk of
      developing lung cancer (O/E 1.5) and malignancy of the female genital tract in
      sisters (O/E 2.8) was slightly increased. In contrast, the risk of urinary tract
      malignancies (O/E 0.3) and other and unknown primary tumors (O/E 0.2) had a lower
      incidence among relatives. However, both the increased and decreased risk of
      nontesticular cancer for first-degree relatives may have been caused by
      misclassification. CONCLUSIONS: TC clusters in families were more pronounced
      among brothers than among fathers and sons. This study supports previous reports
      that families of patients with TC do not seem to be prone to nontesticular
      cancer. Additional investigations in families with TC are recommended to map
      candidate genes for TC.

PMID- 11306396
TI  - Use of porcine small intestinal submucosal graft in the surgical management of
      Peyronie's disease.
AB  - OBJECTIVES: To report the use of a new acellular, xenographic porcine jejunal
      submucosal graft as a closure material for the tunica albuginea after plaque
      incision. METHODS: Twelve patients with at least a 12-month history of Peyronie's
      disease with a penile curvature of 70 degrees or greater were evaluated. Patient
      age ranged from 39 to 61 years (mean 50). Preoperatively, all underwent Doppler
      ultrasound after an intracavernous injection. Lyophilized (freeze-dried) small
      intestinal submucosa immersed in normal saline was used to graft the tunical
      deficit after the plaque incision using a subcoronal incisional approach.
      RESULTS: Surgical correction of the penile curvature was achieved in 11 of 12
      patients. At a mean follow-up of 11 months (range 5 to 20), all patients were
      potent, with one requiring intracavernous injection therapy. One patient
      developed a 60 degrees curvature 6 months postoperatively and required
      reoperation. No reports of penile shortening, pain, infection, hematoma, bulging
      at the graft site, or evidence of a local immunogenic rejection reaction have
      been noted. CONCLUSIONS: At this early stage, acellular porcine jejunal
      submucosal grafts for coverage of cavernosal defects after Peyronie's plaque
      incision allow for satisfactory clinical results. The ease of surgical handling
      and placement and no associated comorbidities from harvesting techniques, coupled
      with no adverse reactions, make this material an anatomic and functional tunical
      substitute.

PMID- 11306399
TI  - Honeymoon impotence: psychogenic or organic in origin?
AB  - OBJECTIVES: Honeymoon impotence is the inability to perform successful sexual
      intercourse during the initial experience, especially during the first nights of
      marriage, and it is relatively frequent in Turkey. We investigated the underlying
      penile vascular abnormalities in patients presenting with honeymoon impotence and
      sought to differentiate between psychogenic and organic etiologies. METHODS:
      Between 1989 and 1999, 90 patients sought urologic help for honeymoon impotence.
      Patient age ranged from 18 to 39 years (mean 28.06 +/- 3.4). All patients were
      given an intracavernous injection of 60 mg papaverine combined with self-manual
      genital stimulation (CIS test) to assess the degree of tumescence. Patients with
      a positive response to the CIS test were later evaluated with nocturnal penile
      tumescence (NPT) monitoring. Patients with a negative response to the CIS test
      and/or NPT monitoring were evaluated further using penile color Doppler
      ultrasound. RESULTS: A psychogenic etiology was found in 61 patients (67.7%), 50
      (55.5%) of whom achieved satisfactory sexual intercourse after intracavernous
      injection. Twenty-five patients (27.7%) exhibited penile vascular abnormalities
      by color Doppler ultrasound. Neurogenic erectile dysfunction was considered in
      the remaining 4 patients (4.4%) with a positive response to the CIS test,
      abnormal findings on NPT monitoring, and a normal vascular system with color
      Doppler ultrasound. CONCLUSIONS: The present study is the first to report penile
      vascular abnormalities in patients presenting with honeymoon impotence, which was
      previously believed to be exclusively psychogenic in origin. The evaluation of
      the penile vascular system in patients with honeymoon impotence may reveal
      underlying penile vascular abnormalities, allowing the choice of the appropriate
      therapeutic option.

PMID- 11306400
TI  - Erectile and ejaculatory dysfunction in a community-based sample of men 50 to 78
      years old: prevalence, concern, and relation to sexual activity.
AB  - OBJECTIVES: To determine the prevalence rates of erectile and ejaculatory
      dysfunction, associated bother, and their relation to sexual activity in a
      population-based sample of elderly men.Methods. Data were collected from 1688 men
      by way of self-administered questionnaires (including the International
      Continence Society male sex questionnaire) and measurements at a health center
      and urology outpatient department. RESULTS: The prevalence of significant
      erectile dysfunction (ie, erections of severely reduced rigidity or no erections)
      increased from 3% in men 50 to 54 years old to 26% in men 70 to 78 years old. In
      the same age strata, the prevalence of significant ejaculatory dysfunction (ie,
      ejaculations with significantly reduced volume or no ejaculations) increased from
      3% to 35%. Pain or discomfort during ejaculation was rare (1%) and independent of
      age. In general, men were more concerned about erectile dysfunction than about
      ejaculatory dysfunction. However, most men had no or only little concern about
      their dysfunction. The percentage of men who reported being sexually active
      declined with increasing age and was lower in men with erectile and ejaculatory
      dysfunction and in men without a partner. In sexually active men, 17% to 28% had
      no normal erections, indicating that with advancing age normal erections are not
      an absolute prerequisite for a sexually active life. CONCLUSIONS: Erectile and
      ejaculatory dysfunction are common in elderly men. The results of this study
      indicate that these conditions are much less of a problem for older men than
      previously suggested.

PMID- 11306401
TI  - Sildenafil citrate effectively reverses sexual dysfunction induced by three
      dimensional conformal radiation therapy.
AB  - OBJECTIVES: We evaluated the response of sildenafil citrate in patients with
      prostate cancer treated with three-dimensional conformal radiation therapy
      (3DCRT) whose sexual function (SF) was known prior to therapy initiation.
      METHODS: From March 1996 to April 1999, 24 men with median age of 68 years (range
      51 to 77) had 3DCRT for localized prostate cancer (median prescribed dose to the
      planning target volume of 70.2 Gy). These men started taking sildenafil for
      relief of sexual dysfunction at a median time of 1 year after completing 3DCRT.
      We used the self-administered O'Leary Brief Sexual Function Inventory to evaluate
      in series SF and overall satisfaction at three time points. These points were (a)
      before initiation of all therapies (3DCRT or hormonal treatment [HT]) for
      prostate cancer, (b) before starting sildenafil (50 mg or 100 mg) but after
      completion of all therapies, and (c) at least 2 months afterward. Rates of SF
      were based on the number of men responding to a given question. We tested for
      significance of these two interventions to change SF by applying the Wilcoxon
      sign rank test. RESULTS: Prior to all treatments, 20 (87%) of 23 men were
      sexually potent, with 8 (36%) of 22 fully potent (little or no difficulty for
      penetration at intercourse). After 3DCRT with or without HT and prior to
      sildenafil use, 13 (65%) of the 20 potent patients remained potent, with only 2
      (11%) of 19 being fully potent. The use of sildenafil citrate resulted in 21
      (91%) of 23 men being potent, with 7 (30%) being fully potent. In 16 men
      responding to the satisfaction question, 10 (63%) and 12 (75%) were mixed to very
      satisfied with their sex life before 3DCRT with or without HT and after
      sildenafil citrate use, respectively. This response corresponded to potency and
      satisfaction scores significantly decreasing and subsequently increasing on
      average by one unit after 3DCRT and sildenafil citrate use, respectively (P
      <0.05). CONCLUSIONS: In men receiving 3DCRT for prostate cancer, these data
      indicate that sildenafil citrate is effective for restoring SF and associated
      satisfaction back to baseline before treatment.

PMID- 11306402
TI  - Determinants of continence in the bladder exstrophy population: predictors of
      success?
AB  - OBJECTIVES: To delineate factors that may predict eventual urinary continence
      after bladder neck reconstruction (BNR) in the bladder exstrophy population.
      METHODS: The records of 65 patients who underwent all phases of bladder exstrophy
      reconstruction at our institution between 1975 and 1997 with greater than 1-year
      follow-up were reviewed and data analyzed. RESULTS: Fifty patients (77%) are
      continent day and night and voiding per urethra without need for augmentation or
      intermittent catheterization. Nine (14%) patients have social continence, dry for
      more than 3 hours during the day. Two patients required continent diversion for
      continence after failed BNR. Four patients are completely incontinent. The mean
      age of BNR was 4 years with a mean and median capacity of 93 and 85 cc (range 45
      to 175). Analysis of bladder capacity measurements prior to BNR revealed that
      patients with a bladder capacity greater than 85 cc median capacity at the time
      of BNR had better outcomes. No correlation was found between the age of BNR and
      obtaining eventual continence. The mean time to daytime continence was 14 months
      (range 4 to 21) and the mean time to nighttime continence was 22 months (range 11
      to 33). CONCLUSIONS: Determinants of continence in the bladder exstrophy
      population are multifactorial. In our experience, 77% of patients are completely
      dry, day and night, and 91% can achieve social continence, being dry for at least
      3 hours. However, with careful evaluation of bladder capacity and bladder growth,
      urinary continence may be improved in this population with better patient
      selection.

PMID- 11306403
TI  - A comprehensive analysis of a tubularized incised plate hypospadias repair.
AB  - OBJECTIVES: To critically evaluate my experience using a modified tubularized
      incised plate (TIP) hypospadias repair. METHODS: Sixty-four boys, 7 months to 11
      years old (mean age 22.9 months), underwent a TIP urethroplasty by a single
      pediatric urologist for primary hypospadias. The hypospadias defects included 53
      distal and 11 midshaft. The incision of the urethral plate was always deep and
      proximal but never extended the entire length of the plate. In 25 cases (39%),
      the incision was less than one half the length of the urethral plate. A two-layer
      urethroplasty was always obtained. A vascularized subcutaneous pedicle was always
      placed onto the urethroplasty. This pedicle was ventrally based in 56 of the
      repairs (87.5%). Postoperative urethral stents were not used in 52 boys (81.3%),
      including 7 with midshaft repairs. All children were scheduled for a
      postoperative evaluation at 1 month. A confidential phone survey was later
      conducted by someone other than the surgeon. The parents were asked if they were
      satisfied or dissatisfied with the direction and caliber of the urinary stream,
      chordee correction, and overall general appearance. RESULTS: The clinical
      evaluation was performed in 54 boys (84.7%) not earlier than 1 month after the
      repair. The examination revealed a conical glans, slit meatus, circumferential
      mucosal collar, and a straight phallus in all cases. No cases of fistula,
      stricture, or dehiscence occurred. A follow-up phone survey 3 to 43 months (mean
      21 months) postoperatively was obtained from the parents of 40 patients. Without
      exception, the parents were satisfied with the urinary stream, chordee
      correction, and overall appearance. CONCLUSIONS: Without incising the entire
      urethral plate and stenting the repair, a TIP urethroplasty can still be expected
      to provide excellent results when correcting distal and midshaft hypospadias.
      Parents were satisfied with the long-term cosmetic and functional results
      obtained with a TIP urethroplasty.

PMID- 11306405
TI  - Medicolegal aspects of testicular torsion.
AB  - OBJECTIVES: Testicular torsion is an active area of medical malpractice
      litigation because of the diagnostic uncertainty, delays in diagnosis and
      treatment, diagnostic errors, and resultant testicular loss. We reviewed this
      topic to determine the nature of patient claims and their clinical and legal
      outcomes. METHODS: All closed case files of a large medical malpractice insurance
      company based in New Jersey involving testicular torsion from the years 1979 to
      1997 were retrospectively reviewed. The following data were collected: patient
      demographics, timing of presentation, initial complaints, diagnosis given,
      consultations obtained, radiographic studies, treatment provided, outcomes, and
      indemnity payments. RESULTS: Thirty-nine cases consisting of 58 individual claims
      were reviewed. Indemnity payments were made in 26 cases (67%), of which 25 (96%)
      were settlements, and 13 cases (33%) ended in favor of the physicians. Five cases
      went to trial, with only one verdict in favor of the plaintiff. The median
      indemnity payment was $45,000. Urologists were named most frequently (48%), and a
      misdiagnosis of epididymitis (61%) was most commonly cited. The mean patient age
      was 24.3 years. Atypical initial complaints were common (46%). Late presentation
      (greater than 8 hours) did not affect the medicolegal outcome. The major
      liabilities for paid claims were an error in diagnosis (74%), a delay in or lack
      of referral (48%), lack of radiologic examination (19%), failure to explore
      (13%), error in surgical technique or judgment (13%), and falsified records
      (10%). CONCLUSIONS: Testicular torsion litigation most often focuses on the
      urologist. Claims are more common in older patients and those with atypical
      complaints. Settlement is the most common outcome, with a fairly standard
      indemnity payment rewarded. The initial treating physician must have a high index
      of suspicion for the diagnosis and refer promptly. In lieu of a definitive
      radiologic study, or when the diagnosis is in question, the urologist should
      strongly consider exploration and should perform contralateral exploration when
      torsion is found.

PMID- 11306407
TI  - Hypospadias: a contemporary epidemiologic assessment.
AB  - OBJECTIVES: To determine whether the incidence of hypospadias is increasing and
      whether racial differences among patients are significant, we evaluated the
      current incidence of hypospadias and patient race in an equal-access healthcare
      system. METHODS: We undertook a retrospective review of discharge records between
      1990 and 1998 from 15 military treatment facilities to determine the total number
      of male live births and the number of male live births with hypospadias reported
      by race (categorized as white, black, Asian, Native American, and unknown).
      RESULTS: Among 99,210 male live births, 709 cases of hypospadias were identified
      (0.7%). Of the total male live births, 68,444 were white, 18,984 were black, 1761
      were Asian, 175 were Native American, and 9846 were unknown, with an incidence of
      hypospadias of 0.8%, 0.6%, 0.5%, 0.6%, and 0.6%, respectively. Racial differences
      were not statistically significant (P = 0.2). CONCLUSIONS: The 0.7% incidence of
      hypospadias detected is near the upper limit of what has been historically
      reported. No significant difference between races was found, but the incidence of
      hypospadias in minorities is higher than previously reported.

PMID- 11306409
TI  - Utility of biofeedback for the daytime syndrome of urinary frequency and urgency
      of childhood.
AB  - OBJECTIVES: To evaluate in a preliminary study the utility of biofeedback for the
      treatment of the daytime syndrome of urinary frequency and urgency of childhood,
      a benign, self-limited condition with symptoms that can last for months or years.
      Observation is a commonly recommended approach to this syndrome because
      medications and other forms of therapy are often not effective. METHODS: During a
      2-year period, 89 children (34 boys and 55 girls) presented with this syndrome.
      Patient age ranged from 4 to 11 years, and duration of symptoms ranged from 1 to
      38 months. All children were evaluated with a history, physical examination,
      urinalysis and culture, and renal and bladder ultrasound scanning. After the
      evaluation, the parents were offered either observation or surface patch
      electromyography biofeedback for the problem. RESULTS: Overall, 84 parents
      (94.3%) selected biofeedback for their child. After 1 month of biofeedback, 34.5%
      of children were able to achieve a 2 to 4-hour voiding interval. After 2 to 4
      months of biofeedback, another 51.2% of patients experienced the same
      improvement. Overall, 85.7% of children who underwent biofeedback had symptom
      improvement. In 14.3% of children, no symptom improvement was noted after 4
      months of biofeedback and these children were considered nonresponders.
      CONCLUSIONS: The results of this study suggest that biofeedback may be a
      treatment option for this disorder and warrants further investigation.

PMID- 11306412
TI  - A fishnet gantry for pediatric extracorporeal shock wave lithotripsy on the
      Sonolith 3000.
AB  - A new type of lithotripsy gantry composed of fishnet and bungee cords has been
      developed to allow proper patient positioning of infants and small children who
      undergo extracorporeal shock wave lithotripsy on the Sonolith 3000 lithotriptor.
      The materials are safe, inexpensive, easy to use, and do not interfere with shock
      wave delivery during a lithotripsy session. The gantry can be used for other
      lithotripsy machines that have a similar construction with a self-contained
      waterbath and a large lithotripsy table window.

PMID- 11306413
TI  - Bladder endometriosis: pertinent clinical images.

PMID- 11306414
TI  - High-flow priapism: a novel way of lateralizing the lesion in radiologically
      inapparent cases.
AB  - High-flow priapism is a rare entity, which is typically diagnosed with the help
      of either color flow Doppler ultrasound or arteriogram. In the case presented,
      both of these diagnostic modalities were unsuccessful in uncovering a vascular
      lesion. The patient underwent an empiric selective embolization of the left
      pudendal artery followed by a repeat angiogram of the right because of persistent
      tumescence. This procedure uncovered a previously unseen arteriolacunar fistula,
      which was treated successfully with a second selective embolization.

PMID- 11306415
TI  - Percutaneous transpouch management of a ureteral stone and ureteral-pouch
      stricture in a pelvic kidney.
AB  - Stones in pelvic kidney collecting systems have not been routinely managed
      percutaneously in most urologic practices. Especially challenging is the
      management of stones in a pelvic kidney collecting system positioned posteriorly
      to a urinary diversion. In the present case, a 32-year-old man with a pelvic
      kidney and continent urinary diversion presented with fever and hydronephrosis.
      Drainage of the kidney was obtained percutaneously by way of an anterior approach
      through-and-through the urinary diversion. The patient was found to have both a
      ureteral stone and a ureteral-pouch anastomotic stricture on subsequent imaging.
      We were able to successfully treat both these problems endoscopically through a
      solitary percutaneous access.

PMID- 11306416
TI  - External beam radiotherapy for synchronous rectal and prostatic tumors.
AB  - Two patients were diagnosed with large rectal tumors and localized prostate
      cancer. The prostate-specific antigen level at diagnosis was 7.9 ng/mL and 9.0
      ng/mL in the 2 patients. Knowledge of the presence of both tumors and their close
      proximity allowed creation of a modified three-dimensional conformal radiotherapy
      plan to treat both tumors. The patients had no evidence of rectal tumor
      recurrence and their prostate-specific antigen level was 0.5 ng/mL and 0.7 ng/mL
      at 1 and 2 years after therapy, respectively. We conclude that efficient,
      effective pelvic irradiation can be designed for synchronous rectal and prostate
      malignancies.

PMID- 11306417
TI  - Primary retroperitoneal seminoma with utrasonically abnormal testes.
AB  - Primary retroperitoneal seminomas account for approximately 2% of all seminomas.
      Differentiating the primary retroperitoneal tumor from a metastatic tumor with an
      occult testicular primary remains difficult despite the availability of
      ultrasonic examination. We present a case of primary retroperitoneal seminoma
      with ultrasonically demonstrated abnormalities in both testes. The patient
      underwent a unilateral orchiectomy and ultrasound-guided biopsy of the opposite
      testis. All surgical specimens were negative for testis cancer. Controversial
      issues in the diagnosis and treatment of primary retroperitoneal germ cell tumors
      are discussed.

PMID- 11306418
TI  - Metastatic renal cell carcinoma neovasculature expresses prostate-specific
      membrane antigen.
AB  - OBJECTIVES: To determine whether the tumor-associated neovasculature of
      metastatic prostate and metastatic conventional (clear cell) renal carcinoma
      express prostate-specific membrane antigen (PSMA). PSMA is a type II integral
      membrane glycoprotein highly expressed in prostate cancer cells and also recently
      discovered to be expressed in the neovasculature of non-prostatic primary
      malignancies. METHODS: We examined metastatic prostate carcinoma (22 patients)
      and metastatic conventional (clear cell) renal carcinoma (20 patients) in various
      anatomic sites, including bone, lymph nodes, liver, lung, and soft tissue. Using
      the biotin-streptavidin method, we performed immunohistochemical reactions with
      the anti-PSMA monoclonal antibodies (mAbs) 7E11 and PM2J004.5 and with the anti
      endothelial cell mAb CD34. RESULTS: Metastatic conventional (clear cell) renal
      carcinoma consistently expressed PSMA. The PM2J004.5 mAb was positive in 20 of 20
      specimens, and the 7E11 mAb was positive in 15 of 20. The anti-PSMA
      immunoreactions with the neovasculature were confirmed by similar staining by the
      anti-CD34 mAb (20 of 20). Although the metastatic prostatic cancer cells
      expressed PSMA in all the specimens, only 2 of 22 had neovasculature PSMA
      expression. CONCLUSIONS: As in primary prostatic adenocarcinomas, the
      neovasculature of metastatic prostate cancer, regardless of site, rarely express
      PSMA. The neovascular endothelial cells of metastatic clear cell renal carcinoma,
      however, express PSMA. This expression may make PSMA an effective target for mAb
      based antineovasculature therapy in metastatic renal carcinoma.

PMID- 11306419
TI  - Comparison of 2-octyl cyanoacrylate adhesive, fibrin glue, and suturing for wound
      closure in the porcine urinary tract.
AB  - OBJECTIVES: To evaluate 2-octyl cyanoacrylate glue (OCG) for wound closure in the
      urinary tract and compare the ability of OCG, fibrin glue (FG), and suture to
      withstand physiologic and supraphysiologic stress, because the use of tissue
      adhesives such as OCG or FG might simplify laparoscopic surgery. METHODS: Female
      domestic pigs (n = 22) underwent a 7.5-cm cystotomy. Of these, 8 had closure with
      OCG and 8 with FG (6 open and 2 laparoscopic in each group). The controls were
      closed with suture (n = 4) or not at all (n = 2). Postoperative catheter drainage
      was not used. At 2 days or 4 weeks postoperatively, the bladders were filled with
      saline to 200 mm Hg pressure and the cystotomy scars inspected for leakage. The
      excised scars were also examined histologically. RESULTS: The 2 OCG and 2 FG pigs
      tested on postoperative day 2 leaked at less than 200 mm Hg. None of the 6 OCG
      pigs tested at 4 weeks leaked at less than 200 mm Hg, including the 2 closed
      laparoscopically. Of the 6 FG pigs intended for study at 4 weeks, 3 (including
      the 2 closed laparoscopically) died from a massive urine leak, 1 tested at 4
      weeks leaked, and 2 did not leak. Thus, 4 of 6 FG pigs leaked by 4 weeks compared
      with none in the OCG group (P = 0.06). The histologic examination was similar in
      the two groups. CONCLUSIONS: Preliminary results suggest that OCG provides enough
      strength to hold together a large bladder wound. In the same model, FG did not
      consistently provide adequate closure.

PMID- 11306420
TI  - Noninvasive detection and prediction of bladder cancer by fluorescence in situ
      hybridization analysis of exfoliated urothelial cells in voided urine.
AB  - OBJECTIVES: To investigate the clinical utility of fluorescence in situ
      hybridization (FISH) of voided urine in the detection of bladder cancer and the
      prediction of its recurrence. METHODS: FISH with centromere-specific probes for
      chromosomes 9 and 17 was performed to evaluate the chromosomal alterations of
      exfoliated urothelial cells in voided urine obtained from 44 patients with
      bladder cancer and 20 controls. The analysis was also performed in 17 patients
      with bladder cancer after complete transurethral resection to prospectively
      determine whether FISH can predict tumor recurrence. RESULTS: The sensitivity to
      detect bladder cancer by FISH analysis (85%) was significantly higher than that
      by urine cytologic examination (32%) and by the bladder tumor antigen test (64%)
      (P <0.0001 and P = 0.026, respectively). The specificity of FISH, cytologic
      analysis, and the bladder tumor antigen test was 95%, 100%, and 80%,
      respectively. Among the 17 patients tested after transurethral resection, 7 of 13
      FISH-positive patients developed tumor recurrence within the 27-month follow-up
      period; none of 4 FISH-negative patients developed recurrence during the same
      period. The recurrence rate in patients with the loss of chromosome 17 was 100%,
      significantly higher than the 23% for patients without this alteration (P =
      0.015). CONCLUSIONS: These findings suggest that FISH analysis of exfoliated
      urothelial cells in voided urine can efficiently detect bladder cancer and
      predict its recurrence.

PMID- 11306421
TI  - Nonadrenergic, noncholinergic relaxation of human isolated corpus cavernosum
      induced by scorpion venom.
AB  - OBJECTIVES: To examine the effects of Tityus serrulatus scorpion venom (TSV) on
      human corpus cavernosum (HCC) using a bioassay cascade. Priapism is occasionally
      observed in scorpion envenomation, mostly in children. METHODS: HCC strips were
      suspended in a cascade system and superfused with aerated and warmed Krebs'
      solution at 5 mL/min. Noradrenaline (3 micromol/L) was infused to induce a
      submaximal contraction of the HCC strips. The release of cyclooxygenase products
      was prevented by infusing indomethacin (6 micromol/L). RESULTS: N(omega)-nitro-L
      arginine methyl ester (10 micromol/L; n = 10) increased the tone of the
      preparations and significantly reduced (P <0.01) the acetylcholine (ACh) and TSV
      induced relaxations. Subsequent infusion of L-arginine (300 micromol/L) partially
      reversed the increased tone and significantly restored the relaxations induced by
      TSV and ACh (P <0.01). The soluble guanylyl cyclase inhibitor ODQ (10 micromol/L;
      n = 8) markedly reduced (P <0.01) the relaxations induced by TSV, ACh, glyceryl
      trinitrate, and bradykinin. 7-Nitroindazole (10 micromol/L; n = 8) inhibited the
      relaxations induced by TSV by 84% (P <0.01) and also caused small, but
      significant, reductions in the ACh and bradykinin-induced HCC relaxations (P
      <0.05). Atropine (1 micromol/L; n = 6) abolished the relaxations evoked by ACh (P
      <0.01), but had no effect on those elicited by TSV. Tetrodotoxin (1 micromol/L; n
      = 6) abolished the relaxations induced by TSV (P <0.01) and also reversed the
      established TSV-induced relaxation (n = 4). CONCLUSIONS: Our results indicate
      that TSV relaxes HCC through the release of nitric oxide from nonadrenergic,
      noncholinergic (NANC) nerves. The elucidation of the mechanism responsible for
      the TSV-induced relaxations might be useful for a better understanding of the
      development of priapism in cases of scorpion envenomation.

PMID- 11306422
TI  - Increased hypoxia correlates with increased expression of the angiogenesis marker
      vascular endothelial growth factor in human prostate cancer.
AB  - OBJECTIVES: To test the hypothesis that increasing levels of hypoxia are
      associated with increased expression of vascular endothelial growth factor (VEGF)
      in prostate cancer by correlating the level of median tissue oxygenation in human
      prostate tumors with the immunohistochemically determined level of VEGF
      expression. METHODS: Custom-made Eppendorf oxygen microelectrodes were used to
      quantitate the pO(2) levels in prostate tumors of 13 men undergoing radical
      prostatectomy. All pO(2) measurements were performed under fluorine-based general
      anesthesia. Paraffin-embedded tumor tissue from these men was analyzed to measure
      the level of VEGF expression by immunohistochemical staining. The significance of
      the associations between the pO(2) levels and VEGF staining were determined by
      the Pearson correlations. RESULTS: The range of the median pO(2) levels (based on
      between 97 and 129 individual measurements) among 13 prostate tumors was 0.5 to
      44.9 mm Hg. The blinded comparison of pO(2) levels and VEGF staining intensity
      demonstrated a significant correlation between increasing hypoxia and the
      percentage of cells staining positive for VEGF (r = -0.721, P = 0.005). This
      correlation was also significant when pO(2) levels were compared with the overall
      immunoreactive score, which takes into account staining intensity (r = -0.642, P
      = 0.018). CONCLUSIONS: To our knowledge, this is the first study demonstrating a
      significant association between increasing levels of hypoxia and increased
      expression of the angiogenesis marker VEGF in human prostate carcinoma. The
      results of our study further support the exploration of antiangiogenesis
      strategies for the treatment of human prostate cancer.

PMID- 11306423
TI  - Muscle-derived cell transplantation and differentiation into lower urinary tract
      smooth muscle.
AB  - OBJECTIVES: To explore the feasibility of primary skeletal muscle-derived cell
      (MDC)-based tissue engineering and gene transfer into the lower urinary tract and
      to explore whether the injected primary skeletal MDCs can persist and
      differentiate into myotubes and myofibers in the bladder wall. METHODS: Primary
      MDCs isolated from normal mice were first transduced with adenovirus encoding the
      expression of the beta-galactosidase reporter gene. Adult severe combined
      immunodeficiency mice (n = 12) were used in this study. The MDCs were injected
      into the right and left lateral bladder walls with a 10-microL Hamilton
      microsyringe. The amount of injected MDCs ranged from 1 to 1.5 x 10(6) cells. The
      tissue was harvested after 5, 35, and 70 days, sectioned, stained for fast myosin
      heavy chain, and assayed for beta-galactosidase expression. RESULTS: We observed
      a large number of cells expressing beta-galactosidase in the bladder wall at each
      time point. Many myotubes and myofibers expressing beta-galactosidase and
      positively stained for fast myosin heavy chain were also seen in the bladder wall
      at 35 and 70 days after injection. Additionally, the size of the injected MDCs
      significantly increased during the course of the study (P <0.05). CONCLUSIONS: We
      have demonstrated the long-term survival and beta-galactosidase expression of
      MDCs injected into the bladder wall. Moreover, our results suggest that some
      injected MDCs can differentiate into myofibers. These results suggest that MDCs
      can be a desirable substance for tissue engineering and an ex vivo method for
      gene transfer into the lower urinary tract.

PMID- 11306424
TI  - Functional effects of unilateral laser papillectomy in the pig.
AB  - OBJECTIVES: To evaluate the use of endoscopic laser papillectomy in a multi
      papillary animal model to unilaterally impair concentrating ability and increase
      the urinary flow rate. METHODS: Domestic pigs underwent unilateral retrograde
      flexible nephroscopy. With a holmium:yttrium-aluminum-garnet laser, varying
      numbers of papillae were ablated. Four weeks after the procedure, renal function
      studies were performed during hydropenia and after hydration, the animals were
      killed, and the kidneys were examined histologically. RESULTS: The urine flow
      rate per 100 mL creatinine clearance was significantly increased in the
      papillectomized kidney compared with the control kidney during hydropenia (1.50
      versus 0.94, P <0.01). The papillectomized kidneys were unable to concentrate the
      urine as well as the control kidneys during both hydropenia (urine osmolarity 430
      versus 534 mOsm/L, P <0.01) and after hydration (329 versus 362 mOsm/L, P =
      0.02). The free water reabsorption per 100 mL creatinine clearance was impaired
      in the papillectomized kidneys compared with the control kidneys (0.48 versus
      1.00, P = 0.02) after hydration. A significant correlation existed between the
      percentage of papillae ablated and the difference in osmolarity between the
      operated and control kidneys (r(2) = 0.50, P = 0.015). Histologic examination
      demonstrated transitional re-epithelialization with moderate collecting duct
      dilation and medullary fibrosis underlying the ablated papillae early in the
      series; however, the histologic features normalized and the creatinine clearance
      was less impaired with a more proficient technique later in the series.
      CONCLUSIONS: Endoscopic laser papillectomy results in increased urine flow and
      impaired urinary concentrating ability. This surgical technique should be
      investigated further for its role in the prevention of nephrolithiasis.

PMID- 11306425
TI  - Age-associated changes in collagen content and its subtypes within rat corpora
      cavernosa with computerized histomorphometric analysis.
AB  - OBJECTIVES: To study the age-associated changes in the percentage of collagen and
      subtypes I, III, and IV within the corpora cavernosa in a rat model. METHODS: The
      corpora cavernosa tissues were obtained from 30 male Wistar rats at three
      different ages. Processed with Masson's trichrome staining for collagen and with
      immunohistochemical staining for the collagen subtypes, the values of the
      collagen percentage, the percentage of area, and relative proportion of each
      collagen subtype within the rat corpora cavernosa were measured using an
      automatic image analysis system. The relationships between an increase in age and
      these parameters were analyzed. RESULTS: The percentage of collagen within the
      corpora cavernosa was higher in the old rats (80 weeks) than in the young (20
      weeks) and intermediate-age (40 weeks) rats (P = 0.02 and P = 0.25, respectively)
      and significantly increased with age (P = 0.021). The values of the percentage of
      area of collagen subtypes III and IV also increased significantly with age (P =
      0.039 and P = 0.019, respectively). The value of the percentage of area of
      collagen subtype I was not significantly increased (P = 0.159). Also, no
      significant differences were found in the relative proportions of all three
      collagen subtypes with age among the three age groups. CONCLUSIONS: The
      percentages of collagen within rat corpora cavernosa significantly increased, but
      not strongly, with age, especially collagen subtypes III and IV. However, the
      relative proportion of each subtype did not change with age. Therefore, we
      conclude that the amount of collagen may only partly contribute to erectile
      dysfunction in the aging process of the rat.

PMID- 11306426
TI  - Conversations with Frank Hinman, Jr.

PMID- 11306427
TI  - IL-9 and lung fibrosis: a Th2 good guy?

PMID- 11306428
TI  - Interleukin-9 reduces lung fibrosis and type 2 immune polarization induced by
      silica particles in a murine model.
AB  - We examined the effect of interleukin (IL)-9, a cytokine active on B and T
      lymphocytes and associated with bronchial asthma, on the development of lung
      fibrosis induced by crystalline silica particles. Therefore, we compared the
      response to silica (1 and 5 mg/animal, intratracheally) in transgenic mice that
      constitutively express high levels of IL-9 (Tg5) and their wild-type counterparts
      (FVB). At 2 and 4 mo after treatment with silica, histologic examination and
      measurement of lung hydroxyproline content showed that the severity of fibrosis
      was significantly less important in Tg5 mice than in their wild-type
      counterparts. Intraperitoneal injection of IL-9 in C57BL/6 mice also reduced the
      amplitude of silica-induced lung fibrosis. The reduction of lung fibrosis by IL-9
      was associated with a significant expansion of the B-lymphocyte population, both
      in bronchoalveolar lavage (BAL) and in the pulmonary parenchyma. In wild-type
      animals, silica-induced fibrosis correlated with markers of a T helper 2-like
      response such as upregulation of IL-4 levels in lung tissue and an increased
      immunoglobulin (Ig) G1/IgG2a ratio in BAL. Immunohistochemical studies
      demonstrated that the upregulation of IL-4 associated with the development of
      fibrosis was mainly localized in inflammatory alveolar macrophages. In transgenic
      mice, the level of IL-4 in lung homogenates was not significantly affected by
      silica treatment, and a reduced IgG1/IgG2a ratio was observed upon treatment with
      silica. The levels of interferon-gamma were significantly decreased after silica
      treatment in both strains. Together, these observations point to an antifibrotic
      effect of IL-9 in pulmonary fibrosis associated with a limitation of the type 2
      polarization which accompanies lung fibrosis.

PMID- 11306429
TI  - Ontogeny of CLCN3 chloride channel gene expression in human pulmonary epithelium.
AB  - Human fetal bronchopulmonary epithelia secrete liquid, and this chloride (Cl)
      dependent process is important for normal lung growth. At the time of birth there
      is a maturational transition from a secretory to an absorptive phenotype. The
      pathways for Cl exit from the apical membrane which are required for fetal lung
      liquid secretion are unknown but are thought to be independent of the cystic
      fibrosis transmembrane conductance regulator. We determined the ontogeny of
      expression of the CLCN family of voltage-dependent Cl channel genes (CLCN2
      through 6, K(a) and K(b)) in the human lung to identify potential pathways for
      pulmonary liquid secretion. Only CLCN3 and CLCN6 messenger RNA were detected by
      Northern analysis of fetal whole lung tissue. Ribonuclease protection assays
      confirmed the expression of CLCN3 and also revealed expression of CLCN2. The
      ontogeny of expression of these two channels was similar, peaking in midgestation
      and declining postnatally. In situ hybridization localized the CLCN2 and CLCN3
      messages to airway and distal pulmonary epithelia and to pulmonary blood vessels.
      We conclude that CLCN3 is expressed in human airway epithelia and expression is
      developmentally regulated. The contribution of these channels to pulmonary
      epithelial liquid transport and lung development remains to be determined.

PMID- 11306430
TI  - Regulated production of the T helper 2-type T-cell chemoattractant TARC by human
      bronchial epithelial cells in vitro and in human lung xenografts.
AB  - The chemokine TARC is a ligand for the chemokine receptor CCR4 expressed on T
      helper (Th)2-type CD4 T cells. Allergic airway inflammation is characterized by a
      local increase in cells secreting Th2-type cytokines. We hypothesized that
      bronchial epithelial cells may be a source of chemokines known to chemoattract
      Th2 cells. Regulated TARC expression was studied using normal human bronchial
      epithelial cells and a human lung xenograft model. TARC expression was increased
      in normal human bronchial epithelial cells in response to tumor necrosis factor
      alpha stimulation, and further upregulation of TARC was observed with interferon
      (IFN)-gamma but not interleukin (IL)-4 costimulation. TARC functions as a nuclear
      factor (NF)-kappa B target gene, as shown by the abrogation of TARC expression in
      response to proinflammatory stimuli when NF-kappa B activation is inhibited. In
      an in vivo model, minimal constitutive TARC expression was observed in human lung
      xenografts. Consistent with our findings in vitro, TARC messenger RNA (mRNA)
      expression was upregulated in the xenografts in response to IL-1, and
      costimulation with IFN-gamma but not IL-4 further increased TARC mRNA and protein
      expression. In addition, bronchoalveolar lavage fluid from asthmatic subjects
      after allergen challenge contained significantly increased levels of TARC,
      suggesting that TARC production by bronchial epithelial cells may play a role in
      the pathogenesis of allergic asthma.

PMID- 11306431
TI  - Antiinflammatory properties of inducible nitric oxide synthase in acute hyperoxic
      lung injury.
AB  - The objective of this study was to determine whether endogenous nitric oxide
      (NO), specifically the inducible NO synthase isoform (iNOS: NOS II), reduces or
      amplifies lung injury in mice breathing at a high oxygen tension. Previous
      studies have shown that exogenous (inhaled) NO protects against hyperoxia-induced
      lung injury, and that endogenous NO derived from iNOS inhibits leukocyte
      recruitment and protects against lung injury induced by lipopolysaccharide. In
      the present study, hyperoxia (> 98% O(2) for 72 h) induced acute lung injury in
      both wild-type and iNOS-deficient mice as determined by elevated albumin and
      lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) and by
      increased extravascular lung water. Lung injury was greater in iNOS-deficient
      mice than in wild-type mice and was associated with an increased number of
      polymorphonuclear leukocytes in BALF. iNOS messenger RNA expression levels
      increased in the lungs of wild-type hyperoxic mice. Nitrotyrosine, a marker of
      reactive NO species, was expressed in both wild-type and iNOS-deficient mice in
      hyperoxia, indicating an iNOS-independent pathway for protein nitration. We
      conclude that iNOS is capable of reducing pulmonary leukocyte accumulation and
      lung injury. The data indicate that iNOS induction serves as a protective
      mechanism to minimize the effects of acute exposure to hyperoxia.

PMID- 11306432
TI  - Microsatellite instability in transforming growth factor-beta 1 type II receptor
      gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis.
AB  - It has been reported that transforming growth factor (TGF)-beta, which plays an
      integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF),
      suppresses proliferation of alveolar epithelial cells in vitro. Although
      hyperplastic lesions of alveolar lining epithelial cells (ALECs) are
      characteristic pathologic features of IPF, the mechanism of their involvement in
      the pathogenesis has not yet been extensively studied. On the assumption that the
      hyperplastic ALECs have escaped from the growth-inhibitory effects of TGF-beta,
      we searched for mutations in the microsatellite of the TGF-beta receptor type II
      (T beta RII) gene. To detect a deletion in the polyadenine tract in exon 3 of the
      T beta RII gene, cells were isolated by microdissection from lung sections of IPF
      patients, and DNA was extracted from these cells and amplified by high-fidelity
      polymerase chain reaction. A total of 121 sites of hyperplastic ALECs from 11 IPF
      patients were analyzed, and a one-base-pair deletion was detected in nine sites
      from five patients. The mutation was also detected in smooth muscle-like cells of
      the thickened pulmonary artery. In some tissue areas where the deletion was
      detected, low T beta RII expression was confirmed by immunohistochemical
      staining. These data suggest that microsatellite instability in the T beta RII
      gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low
      incidence, and that this genetic disorder might play a partial role in the
      pathologic changes of IPF.

PMID- 11306433
TI  - Different accumulation of activated extracellular signal-regulated kinases (ERK
      1/2) and role in cell-cycle alterations by epidermal growth factor, hydrogen
      peroxide, or asbestos in pulmonary epithelial cells.
AB  - The extracellular signal-regulated kinase (ERK) pathway is induced by cytokines
      and oxidative stress. In this study we examined the patterns of localization of
      phosphorylated ERK proteins in relationship to subsequent phenotypic responses by
      the mitogenic agent epidermal growth factor (EGF) (5 ng/ ml); hydrogen peroxide
      (H(2)O(2)) (100 to 300 microM), an inducer of apoptosis; and crocidolite asbestos
      (5 microg/cm(2) dish) in a nontransformed murine alveolar type II epithelial cell
      line (C10). Laser scanning cytometry and flow cytometry were used to determine:
      (1) whether expression of phosphorylated ERKs was cell cycle-related; and (2)
      whether cell-cycle alterations by agents could be modified after addition of the
      mitogen-activated protein kinase/ERK kinase (MEK) 1 inhibitor PD98059. In
      contrast to other stimuli which induced transient increases in phosphorylated
      ERKs, asbestos caused fiber-associated localization of phosphorylated ERKs that
      were elevated from 1 to 24 h (P < or = 0.05), and striking apoptosis followed by
      increased numbers of cells in the S phase at 72 h. In both control and asbestos
      exposed cells, the percentage of phosphorylated ERK-positive cells was greatest
      in cells in the G(2)/M and S phases of the cell cycle. All stimuli caused
      increased proportions of cells in G(2)/M at 24 h that were inhibited by PD98059
      (30 microM). Increases in G(2)/M cells by H(2)O(2) and asbestos also were
      decreased at 48 h by the MEK1 inhibitor. In addition, PD98059 abrogated
      elevations in S-phase cells by EGF and H(2)O(2) at 24 h and by asbestos at 72 h.
      Our results suggest that ERKs mediate cell-cycle alterations during the
      development of epithelial cell apoptosis or proliferation by diverse ERK stimuli.

PMID- 11306434
TI  - High levels of exhaled nitric oxide (NO) and NO synthase III expression in
      lesional smooth muscle in lymphangioleiomyomatosis.
AB  - Smooth-muscle proliferation is the hallmark of lymphangioleiomyomatosis (LAM).
      Although little is known about the pathogenesis of LAM, nitric oxide (NO) is a
      key regulator of smooth-muscle proliferation. NO is linked to the pathogenesis of
      other lung diseases such as asthma, in part by the finding of higher-than-normal
      levels of exhaled NO. If NO were involved in the abnormal smooth-muscle
      proliferation in LAM, we reasoned that exhaled NO from individuals with LAM would
      also differ from that of healthy control subjects. To evaluate this hypothesis,
      we studied exhaled NO in individuals with LAM in comparison with healthy and
      asthmatic women using a chemiluminescent NO analyzer. Women with LAM had higher
      exhaled NO than did healthy women but lower than asthmatic women (NO [parts per
      billion] median (25 to 75%): LAM 8 [7 to 15] [n = 28], control 6 [5 to 8] [n =
      21], asthma 14 [8 to 25] [n = 22]; Kruskal-Wallis P < 0.001). Immunohistochemical
      studies on formalin-fixed, paraffin-embedded sections of surgical and autopsy
      material from lungs of individuals with LAM showed diffuse NO synthase III
      (NOSIII) expression in the lesional smooth muscle of LAM similar to that in the
      vascular endothelium. NOSIII expression was limited to the vascular endothelium
      and bronchial smooth muscle in healthy control lungs. The increased NO and the
      presence of NOSIII expression in lesional smooth muscle warrants further study
      into the potential role for NO in the pathogenesis of LAM.

PMID- 11306435
TI  - Benzene-extracted components are important for the major activity of diesel
      exhaust particles: effect on interleukin-8 gene expression in human bronchial
      epithelial cells.
AB  - Epidemiologic and experimental studies suggest that diesel exhaust particles
      (DEPs) may be related to increasing respiratory mortality and morbidity. We have
      shown that DEPs augmented the production of inflammatory cytokines by human
      airway epithelial cells in vitro. To better understand the mechanisms of their
      proinflammatory activities, we studied the effects of several components
      extracted from DEPs on interleukin (IL)-8 expression in human bronchial
      epithelial cell line BEAS-2B and normal human airway epithelial cells obtained
      from very peripheral airways by an ultrathin bronchoscope. We used several agents
      active on signal transduction pathways in cytokine expression, such as the
      protein kinase C inhibitor staurosporin, antioxidant agents including N-acetyl
      cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), and p38 mitogen-activated
      protein kinase (MAPK) inhibitor SB203580. Benzene-extracted components showed
      effects mimicking DEPs on IL-8 gene expression, release of several cytokines (IL
      8; granulocyte macrophage colony-stimulating factor; and regulated on activation,
      normal T cells expressed and secreted) and nuclear factor (NF)-kappa B
      activation. We also found that NAC, PDTC, and SB203580 suppressed the activities
      of DEPs and their benzene extracts, suggesting the roles of oxidants-mediated NF
      kappa B activation and p38MAPK pathways. Finally, benzo[a]pyrene, one of the
      important compounds included in the benzene component, replicated the activities
      shown by DEPs.

PMID- 11306436
TI  - Relationship of fiber surface iron and active oxygen species to expression of
      procollagen, PDGF-A, and TGF-beta(1) in tracheal explants exposed to amosite
      asbestos.
AB  - To investigate the role of iron and active oxygen species (AOS) in asbestos
      induced fibrosis, we loaded increasing amounts of Fe(II)/Fe(III) onto the surface
      of amosite asbestos fibers and then applied the fibers to rat tracheal explants.
      Explants were harvested after 7 d in air organ culture. Asbestos by itself
      doubled procollagen gene expression, and a further increase was seen with
      increasing iron loading; actual collagen content measured as hydroxyproline was
      increased in a similar pattern. Iron loading also increased gene expression of
      platelet-derived growth factor (PDGF)-A and transforming growth factor (TGF)
      beta(1). Neither asbestos alone nor iron-loaded asbestos affected gene expression
      of PDGF-B, tumor necrosis factor-alpha, or TGF-alpha. The AOS scavenger
      tetramethylthiourea or treatment of fibers with the iron chelator deferoxamine
      prevented asbestos-induced increases in procollagen, PDGF-A, and TGF-beta gene
      expression, whereas glutathione had no effect. The proteasome inhibitor MG-132
      abolished asbestos-induced increases in procollagen gene expression but did not
      affect increases in PDGF-A or TGF-beta(1) expression, whereas the extracellular
      signal-regulated protein kinase (ERK) inhibitor PD98059 had exactly the opposite
      effect. We conclude that surface iron as well as the iron-catalyzed generation of
      AOS play a role in asbestos-induced matrix (procollagen) production and that this
      process is driven in part through oxidant-induced nuclear factor kappa B
      activation. Surface iron and AOS also play a role in PDGF-A and TGF-beta gene
      expression, but through an ERK-dependent mechanism.

PMID- 11306437
TI  - Overexpression of manganese superoxide dismutase protects lung epithelial cells
      against oxidant injury.
AB  - To determine whether overexpression of antioxidant enzymes in lung epithelial
      cells prevents damage from oxidant injury, stable cell lines were generated with
      complementary DNAs encoding manganese superoxide dismutase (MnSOD) and/or
      catalase (CAT). Cell lines overexpressing MnSOD, CAT, or MnSOD + CAT were
      assessed for tolerance to hyperoxia or paraquat. After exposure to 95% O(2) for
      10 d, 44 to 57% of cells overexpressing both MnSOD and CAT and 37 to 47% of cells
      overexpressing MnSOD alone were viable compared with 7 to 12% of empty vector or
      parental cells (P < 0.05). To assess if viable cells were capable of cell
      division after hyperoxic exposures (up to 5 d), a clonogenicity assay was
      performed. The clonogenic potential of cells overexpressing MnSOD + CAT and MnSOD
      alone were significantly better than those expressing CAT alone or empty vector
      controls. In addition, 54 to 72% of cells overexpressing both MnSOD and CAT
      survived in 1 mM paraquat compared with 58 to 73% with MnSOD alone and 27% with
      control cells. Overexpression of CAT alone did not improve survival in hyperoxia
      or paraquat. The combination of MnSOD + CAT did not provide additional protection
      from paraquat. Data demonstrate that overexpression of MnSOD protects cells from
      oxidant injury and CAT offers additional protection from hyperoxic injury when co
      expressed with MnSOD.

PMID- 11306438
TI  - Human lung tissue macrophages, but not alveolar macrophages, express matrix
      metalloproteinases after direct contact with activated T lymphocytes.
AB  - Human alveolar macrophages (AM) and lung tissue macrophages (LTM) have a distinct
      localization in the cellular environment. We studied their response to direct
      contact with activated T lymphocytes in terms of the production of interstitial
      collagenase (MMP-1), 92-kD gelatinase (MMP-9), and of TIMP-1, one of the counter
      regulatory tissue inhibitors of metalloproteinases. Either AM obtained by
      bronchoalveolar lavage or LTM obtained by mincing and digestion of lung tissue
      were exposed for 48 h to plasma membranes of T lymphocytes previously activated
      with phorbol myristate acetate and phytohemagglutinin for 24 h. Membranes of
      activated T cells strongly induced the production of MMP-1, MMP-9, and TIMP-1
      exclusively in LTM but not in AM, whereas membranes from unstimulated T cells
      failed to induce the release of MMPs. Both populations of mononuclear phagocytes
      spontaneously released only small amounts of MMPs and TIMP-1. Similar results
      were obtained when MMP and TIMP-1 expression was analyzed at pretranslational and
      biosynthetic levels, respectively. Blockade experiments with cytokine antagonists
      revealed the involvement of T-cell membrane-associated interleukin-1 and tumor
      necrosis factor-alpha in MMP production by LTM upon contact with T cells. These
      data suggest that the ability of lung macrophages to produce MMPs after direct
      contact with activated T cells is related to the difference in phenotype of
      mononuclear phagocytes and cell localization. In addition, these observations
      indicate that cell-cell contact represents an important biological mechanism in
      potentiating the inflammatory response of mononuclear phagocytes in the lungs.

PMID- 11306439
TI  - Alveolar macrophages, surfactant lipids, and surfactant protein B regulate the
      induction of immune responses via the airways.
AB  - The influences of alveolar macrophages (AM) and pulmonary surfactant on the
      induction of immune responses via the airways were assessed. Mice were depleted
      of their AM by intratracheal instillation of multilamellar vesicles containing
      dichloromethylene-diphosphonate followed by intratracheal instillation of a T
      cell--dependent antigen, trinitrophenyl--keyhole limpet hemocyanin, in vesicles
      of various compositions. The primary immune response was determined in the spleen
      of these animals using an ELI-Spot assay. The secondary immune responses in the
      sera of the mice were assessed using enzyme-linked immunosorbent assays. An
      immune response was detected in animals depleted of their AM and intratracheally
      instilled with antigen in small unilamellar vesicles consisting of either
      phosphatidylcholine cholesterol or surfactant lipids. Incorporation of surfactant
      protein (SP)-B in the antigen vesicles enhanced the immune response, whereas SP-A
      or SP-C in the antigen vesicle did not have an effect. Strikingly, intratracheal
      instillation of SP-B containing antigen vesicles can induce an immunoglobulin M
      immune response in mice without depletion of AM. These results indicate that SP-B
      containing vesicles can enhance the induction of immune responses via the airways
      and further illustrate the important roles of both AM and pulmonary surfactant in
      the pulmonary immune system.

PMID- 11306440
TI  - Acid exposure stimulates the adherence of Streptococcus pneumoniae to cultured
      human airway epithelial cells: effects on platelet-activating factor receptor
      expression.
AB  - To examine the effects of acid exposure on the adherence of Streptococcus
      pneumoniae to cultured human tracheal epithelial cells, cells were exposed to
      acid at various pH levels, and various concentrations of S. pneumoniae were added
      to the culture medium. The number of S. pneumoniae adhering to cultured human
      tracheal epithelial cells increased after acid exposure. Y-24180, a specific
      inhibitor of the receptor for the platelet-activating factor (PAF) and PAF itself
      decreased the number of S. pneumoniae adhering to cultured human tracheal
      epithelial cells after acid exposure. Acid exposure increased the activation of
      transcription factor nuclear factor (NF)-kappa B and the expression of protein
      and messenger RNA (mRNA) of the PAF receptor. The pyrrolidine derivative of
      dithiocarbamate (PDTC), an inhibitor of NF-kappa B, also decreased the number of
      S. pneumoniae adhering to the cultured human tracheal epithelial cells after acid
      exposure. Acid exposure increased the content of interleukin (IL)-1 alpha and IL
      1 beta in the culture supernatants, but monoclonal antibodies to IL-1 alpha and
      IL-1 beta failed to inhibit the increased number of S. pneumoniae adhering to
      cultured human tracheal epithelial cells after acid exposure. These findings
      suggest that acid exposure stimulates the adherence of S. pneumoniae to the
      airway epithelial cells via increases in PAF receptors. Increases in PAF receptor
      expression may be, in part, mediated via activation of transcription factors and
      subsequent PAF receptor mRNA expression by acid exposure. Increased adherence of
      S. pneumoniae may be one of the reasons why pneumonia develops after gastric
      juice aspiration.

PMID- 11306441
TI  - Genetic ablation of the src kinase p59fynT exacerbates pulmonary inflammation in
      an allergic mouse model.
AB  - p59fynT is a protein tyrosine kinase in the src family that has been associated
      with and believed to function in the signaling of many receptors, including the T
      cell receptor. A role for the kinase in antigen-driven pulmonary inflammation was
      examined using mice whose p59fynT gene had been genetically ablated. FynKO mice
      that were sensitized to ovalbumin exhibited a marked increase in bronchoalveolar
      lavage eosinophils and cytokines, including interleukin (IL)-4 and IL-5, relative
      to wild-type mice in response to antigen aerosol exposure. Ovalbumin-stimulated
      IL-5 production was also increased in cultured splenocytes derived from fynKO
      mice relative to wild-type mice, whereas interferon-gamma levels were unchanged.
      Diminished concanavalin A--stimulated IL-4 levels from fynKO splenocytes were
      consistent with reduced serum immunoglobulin (Ig)E levels observed in
      sensitized/saline aerosol-challenged animals and may reflect defective natural
      killer 1.1(+) T cell development. Normalization of IgE levels in sensitized fynKO
      mice relative to wild-type mice occurred after repeat antigen challenge, which
      suggests a secondary source of IL-4. Overall, these data demonstrate fyn is a
      negative regulator of allergic airway inflammation in mice because its absence
      promotes a shift to a T helper-2 phenotype that may reflect the kinase's role in
      T-cell receptor signaling.

PMID- 11306442
TI  - Carbohydrate recognition domain of surfactant protein D mediates interactions
      with Pneumocystis carinii glycoprotein A.
AB  - Pneumocystis carinii continues to cause severe pneumonia in immunocompromised
      patients. Surfactant protein D (SP-D), a lung collectin, markedly accumulates
      during P. carinii pneumonia and binds to glycoprotein A (gpA) on the surface of
      P. carinii, thereby enhancing interactions with alveolar macrophages. Herein, we
      report the structural basis of the interaction of SP-D with gpA. We demonstrate
      that natural SP-D binds to purified gpA in the presence of 2 mM calcium in a
      saturable, concentration-dependent manner, which is abolished by 10 mM
      ethylenediaminetetraacetic acid. Increasing concentrations of calcium under
      otherwise cation-free conditions significantly enhance SP-D binding to gpA,
      whereas manganese and magnesium cations have minimal effect. Maximal SP-D binding
      occurs at pH 7.4, with significant inhibition at pH 4. SP-D binding to gpA is
      also competitively inhibited by maltose>glucose>mannose>N-acetyl-glucosamine.
      Comparison of the binding of various natural and recombinant forms of SP-D to gpA
      reveals that the number of carbohydrate recognition domains (CRDs) in a given SP
      D form determines the relative extent of binding to gpA. Maximal binding is
      observed with natural SP-D (dodecamers and higher order SP-D complexes) followed
      by recombinant dodecamers. In contrast, recombinant full-length trimers exhibit
      substantially less binding, which is similar to that observed with a recombinant
      truncated molecule consisting of the CRD and neck regions, and containing trimers
      of this portion of the molecule. Taken together, these findings strongly indicate
      that the CRD of SP-D mediates interaction with P. carinii gpA through its
      attached oligosaccharides and that the extent of SP-D binding to P. carinii is
      greatest with dodecamers and higher order forms of SP-D.

PMID- 11306444
TI  - Quartz exposure of the rat lung leads to a linear dose response in inflammation
      but not in oxidative DNA damage and mutagenicity.
AB  - Exposure to quartz and high concentrations of other poorly soluble particles can
      lead to the development of lung tumors in the rat. The mechanisms involved in
      particle-induced carcinogenesis seem to include inflammation-associated
      production of reactive oxygen species (ROS) and DNA damage. ROS induce 8
      oxoguanine (8-oxoGua) and a panel of other oxidation products in DNA. In
      proliferating cells such DNA lesions can lead to various types of mutations,
      which might be critical for cancer-related genes with respect to tumor formation.
      Quartz is known to mediate the induction of 8-oxoGua in the nuclear DNA of lung
      cells when applied to the lung of rats. We have investigated the time- and dose
      dependent biologic effects of quartz and, as a control, corundum, on cell
      proliferation and various pulmonary inflammation and toxicity markers in rat
      bronchoalveolar lavage fluid (BALF); on the induction of 8-oxoGua in the DNA of
      rat lung cells; and on the cellular levels of p53 wild-type and p53 mutant (mut)
      protein. Rats were exposed by intratracheal instillation to various amounts of
      quartz (0.3, 1.5, or 7.5 mg/rat) or corundum (0.3, 1.5, or 7.5 mg/rat) and
      measured at Days 7, 21, and 90 after exposure. Corundum had no adverse effects
      except a slight elevation of 8-oxoGua at a dose of 7.5 mg/rat. However,
      significant changes in the BALF were detected at all quartz doses. 8-oxoGua was
      significantly increased only at 1.5 and 7.5 mg quartz/rat. The amount of cells
      with detectable p53 wild-type protein levels was increased at 1.5 and 7.5 mg
      quartz/rat at 7 and 21 d. Elevated amounts of cells with enhanced p53 mut protein
      levels were measured at all time points after instillation of 7.5 mg quartz/rat.

PMID- 11306443
TI  - Glucocorticoid treatment increases inhibitory m(2) muscarinic receptor expression
      and function in the airways.
AB  - M(2) muscarinic receptors on parasympathetic nerve endings inhibit acetylcholine
      release in the airways. In this study, the effects of dexamethasone on M(2)
      receptors in vivo and in primary cultures of airway parasympathetic neurons were
      tested. Treating guinea pigs with dexamethasone (0.1 mg/kg, daily for 2 d)
      substantially increased inhibitory M(2) muscarinic receptor function, decreasing
      airway responsiveness to electrical stimulation of the vagi. At the same time,
      dexamethasone decreased the response to acetylcholine but not to methacholine,
      suggesting that cholinesterase activity was increased. When both cholinesterase
      and M(2) receptors were blocked (using physostigmine and gallamine, respectively)
      vagally induced bronchoconstriction was increased to control values. In primary
      cultures of airway parasympathetic neurons, dexamethasone significantly decreased
      the release of acetylcholine in response to electrical stimulation. Blocking
      inhibitory M(2) receptors using atropine (10(-5) M) increased acetylcholine
      release. After the M(2) receptors were blocked there was no difference in
      acetylcholine release between control and dexamethasone-treated cultures. M(2)
      receptor gene expression was increased by more than fivefold in dexamethasone
      treated cultures. Immunostaining of dexamethasone-treated neurons demonstrated
      more intense staining. Thus, decreased vagally mediated reflex
      bronchoconstriction after glucocorticoid treatment may be the result on increased
      M(2) receptor expression and function as well as increased degradation of
      acetylcholine by cholinesterase.

PMID- 11306445
TI  - 4-Hydroxy-2-nonenal increases gamma-glutamylcysteine synthetase gene expression
      in alveolar epithelial cells.
AB  - Previous studies from this laboratory demonstrated that 4-hydroxy-2-nonenal
      (4HNE), a lipid peroxidation product, induces expression of gamma
      glutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo
      glutathione (GSH) synthesis, in rat alveolar epithelial L2 cells. The present
      study demonstrates that 4HNE also induces GCS in primary cultured alveolar
      epithelial type II (AT2) cells. Enzyme activity, protein content, and messenger
      RNA levels of both the catalytic (GCS-HS) and regulatory (GCS-LS) subunits were
      significantly increased in AT2 cells treated with 5 or 10 microM 4HNE, the same
      concentrations that induced GCS expression in L2 cells. As in L2 cells, 4HNE
      induced a greater AT2-cell increase in GCS-LS than in GCS-HS, suggesting that
      modulation of GCS-LS may play a dominant role in regulating GSH concentration in
      response to oxidative stress. Additional studies using mitogen-activated protein
      kinase pathway inhibitors showed that induction by 4HNE of GCS-HS, but not GCS
      LS, was mediated through activation of the extracellular regulated kinase pathway
      in L2 cells. The results demonstrate that L2 cells maintain the same
      responsiveness to oxidant challenge as do primary cultured AT2 cells in terms of
      increasing GSH synthetic capacity, and that different pathways are involved in
      the induction of two GCS subunits by 4HNE.

PMID- 11306446
TI  - The association of human papillomavirus 16/18 infection with lung cancer among
      nonsmoking Taiwanese women.
AB  - Lung cancer is the leading cause of cancer death in Taiwanese women since 1982.
      High lung cancer mortality ratio of male:female in Taiwan (2:1) was observed,
      although less than 10% of female lung cancer patients are smokers. Until now, the
      etiological factor remains unknown. We hypothesize that high-risk human
      papillomavirus (HPV) 16/18 may be associated with lung cancer development based
      on high prevalence of p53 negative immunostainings in female lung tumors compared
      with that of male lung tumors. In this study, 141 lung cancer patients and 60
      noncancer control subjects were enrolled to examine whether HPV 16/18 DNA existed
      in lung tumor and normal tissues by nested PCR and in situ hybridization (ISH),
      respectively. The concordant detection of HPV 16 and 18 DNA between nested PCR
      and ISH method was 73 and 85.5%, respectively. Our data showed that 77 (54.6%) of
      141 lung tumors had HPV 16/18 DNA compared with 16 (26.7%; P = 0.0005) of 60
      noncancer control subjects. In addition, ISH data showed that HPV 16/18 DNA was
      uniformly located in lung tumor cells, but not in the adjacent nontumor cells.
      When study subjects were stratified by gender, age, and smoking status,
      nonsmoking female lung cancer patients who were older than 60 years old had
      significantly high prevalence of HPV 16/18 infection. The odds ratio of HPV 16/18
      infection of nonsmoking female lung cancer patients is much higher at 10.12 (95%
      confidence interval, 3.88-26.38) compared with 1.98 (95% confidence interval,
      0.84-4.76) of nonsmoking male lung cancer patients. This result strongly suggests
      that HPV infection is associated with lung cancer development of nonsmoking
      female lung cancer patients. The high prevalence of HPV 16/18 infection may
      explain to a certain extent why Taiwanese women nonsmokers had a higher lung
      cancer mortality rate.

PMID- 11306447
TI  - Highly specific tumor binding of a 213Bi-labeled monoclonal antibody against
      mutant E-cadherin suggests its usefulness for locoregional alpha
      radioimmunotherapy of diffuse-type gastric cancer.
AB  - A monoclonal antibody (E-cadherin delta 9-1) directed against a characteristic E
      cadherin mutation (in-frame deletion of exon 9), found in diffuse-type gastric
      cancer but not in any normal tissue, was conjugated with the high linear energy
      transfer alpha-emitter 213Bi and tested for its binding specificity in s.c. and
      i.p. nude mice tumor models. After intratumoral application in s.c. tumors
      expressing mutant E-cadherin, the 213Bi-labeled antibody was specifically
      retained at the injection site as shown by autoradiography. After injection into
      the peritoneal cavity, uptake in small i.p. tumor nodules expressing mutant E
      cadherin was 17-fold higher than in tumor nodules expressing wild-type E-cadherin
      (62% injected dose/g versus 3.7% injected dose/g). 78% of the total activity in
      the ascites fluid was bound to free tumor cells expressing mutant E-cadherin,
      whereas in control cells, binding was only 18%. The selective binding of the
      213Bi-labeled, mutation-specific monoclonal antibody E-cadherin delta 9-1
      suggests that it will be successful for alpha-radioimmunotherapy of disseminated
      tumors after locoregional application.

PMID- 11306449
TI  - Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in
      hereditary nonpolyposis colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer syndrome is associated with an
      inherited predisposition to primarily colorectal cancer (CRC) and endometrial
      cancer (EC); however, the biological basis of the organ involvement remains
      unknown. As an attempt to explore whether the expression levels of MLH1, MSH2,
      and MSH6 may play a role, we used immunohistochemistry to study 42 ECs and 35
      CRCs from patients carrying the same predisposing mutations. Among MSH2 mutation
      carriers, MLH1 was expressed in both tumor types, whereas MSH2 and, in many
      cases, also MSH6, were absent. Remarkably, among MLH1 mutation carriers, 54% of
      ECs (21 of 39), but none of the CRCs (0 of 32), lacked the MSH2 and/or MSH6
      protein in addition to lacking MLH1 protein expression. These results demonstrate
      a marked difference between hereditary nonpolyposis colorectal cancer-related
      CRCs and ECs and suggest that the development of the latter tumors is selectively
      associated with the MSH2/MSH6 protein complex deficiency.

PMID- 11306448
TI  - A light, nontoxic interleukin 12 protocol inhibits HER-2/neu mammary
      carcinogenesis in BALB/c transgenic mice with established hyperplasia.
AB  - With a slight asynchronous but consistent progression, all of the mammary glands
      of female BALB/c mice transgenic for the transforming rat HER-2/neu oncogene
      progress to atypical hyperplasia and to invasive carcinoma. Previous studies have
      shown that chronic administration of interleukin (IL) 12 started at the 2nd week
      of age hampers this progression because of its ability to inhibit tumor
      angiogenesis and activate a nonspecific immune response. Here we show that a
      similar inhibition is achieved when 7-week-old mice with fully blown atypical
      hyperplasia receive a weekly injection of 100 ng IL-12 for 16 times. This lower
      dose and later IL-12 administration induces high and sustained levels of serum
      IFN-gamma equivalent to those elicited by more frequent administrations. A lower
      dose and less toxic treatment may thus be envisaged as a possible option in the
      management of preneoplastic mammary lesions.

PMID- 11306450
TI  - p14ARF silencing by promoter hypermethylation mediates abnormal intracellular
      localization of MDM2.
AB  - The INK4a/ARF locus encodes two distinct tumor suppressors, p16INK4a and p14ARF.
      Although the contribution of p16INK4a to human tumorigenesis through point
      mutation, deletion, and hypermethylation has been widely documented, little is
      known about specific p14ARF lesions and their consequences. Recent data indicate
      that p14ARF suffers inactivation by promoter hypermethylation in colorectal
      cancer cells. Because it is known that p14ARF prevents MDM2 nucleocytoplasmic
      shuttling and thus stabilizes p53 by attenuating MDM2-mediated degradation, we
      studied the relationship of p14ARF epigenetic silencing to the expression and
      localization of MDM2 and p53. Cancer cell lines with an unmethylated p14ARF
      promoter showed strong nuclear expression of MDM2, whereas in a colorectal cell
      line with p14ARF hypermethylation-associated inactivation, MDM2 protein was also
      seen in the cytosol. Treatment with the demethylating agent 5-aza-2'
      deoxycytidine was able to reinternalize MDM2 to the nucleus, and p53 expression
      was restored. No apparent changes in retinoblastoma localization were observed.
      We also studied the profile of p14ARF promoter hypermethylation in an extensive
      collection of 559 human primary tumors of different cell types, observing that in
      colorectal, gastric, renal, esophageal, and endometrial neoplasms and gliomas,
      aberrant methylation of p14ARF was a relatively common epigenetic event. MDM2
      expression patterns revealed that lack of p14ARF promoter hypermethylation was
      associated with tumors showing exclusive nuclear MDM2 staining, whereas MDM2
      cytosolic staining was frequently observed in neoplasms with aberrant p14ARF
      methylation. Taken together, these data support that epigenetic silencing of
      p14ARF by promoter hypermethylation is a key mechanism in the disturbance of the
      MDM2 nuclear localization in human cancer.

PMID- 11306451
TI  - Mutations in the carcinoembryonic antigen gene in colorectal cancer patients:
      implications on liver metastasis.
AB  - Carcinoembryonic antigen (CEA) expression is used clinically to monitor patients
      with colorectal and other cancers. A subset of patients have extraordinarily high
      CEA levels that cannot be attributed solely to tumor load. We have shown
      mutations in the region of CEA (PELPK motif) responsible for its hepatic
      clearance in three of eight patients with high CEA levels. We used denaturing
      high-performance liquid chromatography to provide evidence of polymorphism in
      these patients. These mutations were scored by DNA cycle sequencing and shown to
      be heterozygous. The patients with mutations in the PELPK motif showed remarkably
      reduced circulatory clearance rates in an animal model. A patient without
      mutation in the region showed normal clearance rates. Mutations in PELPK may
      affect structural stability and binding affinity to the Kupffer cell receptor in
      the liver. These studies have implications for the role of CEA as a facilitator
      of hepatic metastasis.

PMID- 11306452
TI  - Identification of breast cancer resistant protein/mitoxantrone
      resistance/placenta-specific, ATP-binding cassette transporter as a transporter
      of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole
      structure.
AB  - The antitumor drugs NB-506 and J-107088 are potent topoisomerase I inhibitors
      with an indolocarbazole structure. To clarify the factors involved in resistance
      to these drugs, we established two NB-506-resistant mouse fibroblast cell lines
      (LY/NR1 and LY/NR2), a human colon carcinoma cell line (HCT116/NR1), and a lung
      cancer cell line (PC13/NR1). These cell lines were highly resistant to NB-506 and
      J-107088, and LY/NR2 cells showed markedly reduced accumulation and strong efflux
      of NB-506, suggesting activation of a drug efflux pump in the resistant cells. To
      identify the molecules responsible for efflux of NB-506, we compared the gene
      expressions of the mouse resistant LY/NR1 cells, LY/NR2 cells, and their parental
      cells by oligonucleotide microarray. Of 34,020 genes analyzed, we found that an
      ATP-binding cassette transporter BCRP/MXR/ABCP (BCRP) gene showed the highest
      increase in the expression, 31-fold higher in the LY/NR2-resistant cells than in
      their parental cells. The selective overexpression of this gene was also detected
      in the two human resistant cell lines, suggesting the involvement of breast
      cancer resistant protein (BCRP) in the resistance and efflux of these drugs.
      Finally, a PC-13 cell line transfected with BCRP expression vector displayed 22-
      and 17-fold resistance to NB-506 and J-107088 and enhanced efflux activity of J
      107088. However, the transfectants were not resistant to mitoxantrone or
      topotecan, the drugs previously thought to be the substrates of BCRP. Thus, our
      study presents a novel mechanism of drug resistance mediated by BCRP.

PMID- 11306454
TI  - Ultraviolet irradiation induces BRCA2 protein depletion through a p53-independent
      and protein synthesis-dependent pathway.
AB  - It has been suggested that BRCA2, the protein product of the breast cancer
      susceptibility gene BRCA2, is involved in DNA damage repair. It is therefore
      likely that BRCA2 plays a role in a signaling pathway induced by DNA-damaging
      agents. To test this possibility, we examined the alteration of the BRCA2 protein
      level in human cell lines after UV irradiation. We found that UV irradiation down
      regulated BRCA2 in a dose-dependent manner in all cell lines tested. The down
      regulation of BRCA2 occurred soon (within 4 h) after UV treatment. Surprisingly,
      down-regulation of BRCA2 by UV does not require functional p53, which has been
      suggested to be required for the down-regulation of BRCA1 and BRCA2 mRNAs by DNA
      damaging agents. Moreover, the proteosome- and calpain-mediated protein
      degradation pathways do not have an important role in the UV-induced BRCA2
      depletion. However, blocking protein synthesis temporally inhibited the depletion
      of BRCA2 and BRCA1 in some cell lines. Ectopic expression of BRCA2 in cells
      increased resistance of cells to high-dose UV irradiation. These results
      demonstrate that BRCA2 is involved in a DNA-damaging signaling pathway induced by
      UV radiation and that expression of BRCA2 can protect cells from UV-mediated cell
      death.

PMID- 11306453
TI  - Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression
      is inversely related to histological pattern in advancing human prostatic
      cancers.
AB  - We have shown recently (B. A. Yoshida et al., Cancer Res., 59: 5483-5487) that
      mitogen-activated protein kinase kinase 4 (MKK4) can suppress AT6.1 rat prostate
      cancer metastases in vivo. Evaluation of the expression of components of the MKK4
      signaling cascade showed a loss or down-regulation of expression of MKK4 or c
      Jun, a downstream mediator of MKK4, in six of eight human prostate cancer cell
      lines. Given these findings, we next assessed whether MKK4 dysregulation occurs
      during the development of clinical prostate cancer. Immunohistochemical studies
      showed high levels of MKK4 expression in the epithelial but not the stromal
      compartment of normal prostatic tissues. In neoplastic tissues, a statistically
      significant, direct, inverse relationship between Gleason pattern and MKK4 was
      established. These results demonstrate that MKK4 protein is consistently down
      regulated during prostate cancer progression and support a role for dysregulation
      of its signaling cascade in clinical disease. To test the possibility that down
      regulation of MKK4 protein is the result of allelic loss, metastatic prostate
      cancer lesions were examined for loss of heterozygosity (LOH) within the MKK4
      locus (D17S969). These studies showed a 31% (5 of 16) LOH of MKK4 that is not
      associated with coding region mutations, which suggests that the nucleotide
      sequence of the gene in the remaining allele is infrequently mutated.

PMID- 11306455
TI  - Extracellularly tumor-activated prodrugs for the selective chemotherapy of
      cancer: application to doxorubicin and preliminary in vitro and in vivo studies.
AB  - Oligopeptidic derivatives of anthracyclines unable to penetrate cells were
      prepared and screened for their stability in human blood and their reactivation
      by peptidases secreted by cancer cells. N-beta-alanyl-L-leucyl-L-alanyl-L-leucyl
      doxorubicin was selected as a new candidate prodrug. The NH2-terminal beta
      alanine allows a very good blood stability. A two-step activation by peptidases
      found in conditioned media of cancer cells ultimately yields N-L-leucyl
      doxorubicin. In vitro, when MCF-7/6 cancer cells are exposed to the prodrug, they
      accumulate about 14 times more doxorubicin than MRC-5 normal fibroblasts, whereas
      when exposed to doxorubicin the uptake is slightly higher in fibroblasts than in
      MCF-7/6 cells. This increased specificity of the prodrug over doxorubicin was
      confirmed in cytotoxicity assays using the same cell types. In vivo, the prodrug
      proved about nine times less toxic than doxorubicin in the normal mouse and also
      much more efficient in two different experimental chemotherapy models of human
      breast tumors.

PMID- 11306456
TI  - CpG island methylation in premalignant stages of gastric carcinoma.
AB  - There are limited reports on methylation analysis of the premalignant lesions of
      gastric carcinoma thus far. This is despite the fact that gastric carcinoma is
      one of the tumors with a high frequency of CpG island hypermethylation. To
      determine the frequency and timing of hypermethylation during multistep gastric
      carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and
      carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1),
      death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue
      inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation
      specific PCR. Three different classes of methylation behaviors were found in the
      five tested genes. DAP-kinase was methylated at a similar frequency in all four
      stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%,
      respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%,
      respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16
      were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in
      all stages but showed a marked increase in hypermethylation frequency from
      chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7%
      and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%,
      respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1,
      THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal
      metaplasia and adenomas, but the p16 hypermethylation frequency tended to be
      higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The
      average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per
      sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas,
      respectively. This shows a marked increase in methylated genes from non
      metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from
      premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG
      island hypermethylation occur early in multistep gastric carcinogenesis and tend
      to accumulate along the multistep carcinogenesis.

PMID- 11306457
TI  - Reduced 1alpha-hydroxylase activity in human prostate cancer cells correlates
      with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition.
AB  - Evidence from epidemiological, molecular, and genetic studies suggests a role for
      vitamin D in the development and/or progression of prostate cancer. In
      experimental models and clinical trials, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      was shown to exert antiproliferative, prodifferentiating, and
      antimetastatic/invasive effects on prostatic epithelial cells. Because the direct
      clinical application of 1,25(OH)2D3 is limited by the major side effect of
      hypercalcemia, we investigated the potential therapeutic utility of its less
      calcemic precursor, 25-hydroxyvitamin D3 [25(OH)D3], which is converted locally
      within the prostate to 1,25(OH)2D3 by 1alpha-hydroxylase. Quantification of
      1alpha-hydroxylase activity in human prostatic epithelial cells by enzyme
      substrate reaction analyses revealed a significantly decreased activity in cells
      derived from adenocarcinomas compared with cells derived from normal tissues or
      benign prostatic hyperplasia (BPH). In growth assays, we found that 25(OH)D3
      inhibited growth of normal or BPH cells similarly to 1,25(OH)2D3. In contrast, in
      primary cultures of cancer cells and established cell lines, the
      antiproliferative action of 25(OH)D3 was significantly less pronounced than that
      of 1,25(OH)2D3. Our results indicate that growth inhibition by 25(OH)D3 depends
      on endogenous 1alpha-hydroxylase activity, and that this activity is deficient in
      prostate cancer cells. This finding has ramifications for both the prevention and
      therapy of prostate cancer with vitamin D compounds.

PMID- 11306458
TI  - Progression and enhancement of metastatic potential after exposure of tumor cells
      to chemotherapeutic agents.
AB  - Data presented in this report indicate short-term in vitro treatment of
      nonmetastatic MCF-7 breast carcinoma cells with the chemotherapeutic agents-,
      Adriamycin and/or 5-fluoro-2'-deoxyuridine (FUdR), induced changes in the
      expressed phenotype. Cells treated sequentially with Adriamycin and FUdR
      expressed a metastatic phenotype. The results also show short-term exposure of
      MCF-7 cells to either Adriamycin or FUdR rapidly increases, in a dose-dependent
      manner, the release of the angiogenic cytokine, interleukin-8(IL-8), which is
      released at consistently higher levels in metastatic cell lines. Cell populations
      surviving a single treatment with either one or both of these chemotherapeutic
      agents continue to stably release IL-8. Survivors of sequential treatment with
      Adriamycin and FUdR (MCF-7 A/F) release the most IL-8 and express the greatest
      phenotypic variance from the parental, MCF-7 cells. Parental MCF-7 cells and MCF
      7 A/F cells both form primary tumors when used in an orthotopic tumor model;
      however, the MCF-7 A/F tumors have a more rapid initial growth phase in situ and
      give rise to spontaneous lung metastases within 10 weeks. A cell line that is
      established from lung metastases releases more IL-8, has a higher cloning
      efficiency, and forms looser colonies in monolayer than do their parental cells.
      These experiments indicate the in vitro exposure of tumor cells to
      chemotherapeutic agents either selects more aggressive cells or enhances the
      metastatic potential of the surviving cells.

PMID- 11306459
TI  - A unique pathway in the homing of murine multiple myeloma cells: CD44v10 mediates
      binding to bone marrow endothelium.
AB  - Our group recently reported that multiple myeloma (MM) cells preferentially
      adhere to bone marrow (BM) endothelial cells and selectively home to the BM,
      suggesting the involvement of specific adhesive interactions in this process. The
      highly regulated expression of CD44 variant isoforms (CD44v) on the MM cells
      makes them good candidate adhesion molecules involved in this homing. We
      addressed this in the 5T experimental mouse model of myeloma. Fluorescence
      activated cell sorting analysis demonstrated expression of CD44v6, CD44v7, and
      CD44v10 on the in vivo growing 5T2MM and 5T33MM myeloma lines. Antibody blocking
      experiments revealed the involvement of CD44v10 in the adhesion of 5T2MM and
      5T33MM cells to BM endothelial cells. Coinjection of anti-CD44v10 antibodies with
      the myeloma cells into syngeneic mice demonstrated a selective blocking of their
      BM homing which resulted in a decreased BM tumor load and serum paraprotein at
      the end stage of the disease. The highly restricted expression of CD44v10 on MM
      cells, the blocking of MM adhesion to BM endothelial cells and of homing to BM by
      anti-CD44v10, and the decreased BM tumor load suggest that myeloma cells home to
      the BM via interactions mediated by this specific region of the adhesion molecule
      CD44.

PMID- 11306460
TI  - Norepinephrine-induced migration of SW 480 colon carcinoma cells is inhibited by
      beta-blockers.
AB  - Beta-adrenoceptors are highly expressed on SW 480 colon carcinoma cells as was
      assessed by flow cytometry. We investigated the influence of norepinephrine on
      the migration of these cells using time-lapse videomicroscopy. Norepinephrine
      treatment increased the locomotor activity within the population from 25%
      spontaneously locomoting cells to 65% locomoting cells. The beta1/2-blocker
      propranolol but not the beta1-blocker atenolol inhibited this increase. The
      intracellular signaling solely of norepinephrine-induced locomotion involved
      protein tyrosine kinase activity, whereas both spontaneous and norepinephrine
      induced migration were reduced by inhibiting phospholipase Cgamma and protein
      kinase Calpha activity. In summary, norepinephrine-induced locomotion of SW 480
      cells is beta2-adrenoceptor mediated and distinct from spontaneous locomotion
      concerning the PTK involvement.

PMID- 11306461
TI  - Cloning and characterization of CLLD6, CLLD7, and CLLD8, novel candidate genes
      for leukemogenesis at chromosome 13q14, a region commonly deleted in B-cell
      chronic lymphocytic leukemia.
AB  - Chromosome 13q14 deletions constitute the most common structural aberration in B
      cell chronic lymphocytic leukemia (B-CLL). We constructed a high-resolution
      physical map covering the critical deleted region in B-CLL at 13q14 and flanking
      sequences. The order and position of both genomic markers and known genes were
      determined precisely. Three novel genes, CLLD6, CLLD7, and CLLD8, were isolated
      and characterized. The predicted protein sequence of CLLD6 revealed no homology
      with known proteins. However, both CLLD7 and CLLD8 predicted proteins contain
      known functional domains. CLLD7 has both an RCC1 and a BTB domain, and could thus
      be involved in cell cycle regulation by chromatin remodeling. CLLD8 contains a
      methyl-CpG binding, a preSET and a SET domain, suggesting that CLLD8 might be
      associated with methylation-mediated transcriptional repression. Mutation
      analysis of hematopoietic tumor cell lines and B-CLL tumor samples revealed no
      point mutations within the coding region of these three novel genes. The
      functional domains present within CLLD7 and CLLD8 suggest that the proteins may
      be involved in critical cellular processes such as cell cycle and transcriptional
      control and could therefore be directly or indirectly involved in leukemogenesis.

PMID- 11306462
TI  - Caspase-3 activation by lysosomal enzymes in cytochrome c-independent apoptosis
      in myelodysplastic syndrome-derived cell line P39.
AB  - In most cases, apoptosis is considered to involve mitochondrial dysfunction with
      sequential release of cytochrome c from mitochondria, resulting in activation of
      caspase-3. However, we found that etoposide induced apoptosis in P39 cells, a
      myelodysplastic syndrome-derived cell line, without the release of cytochrome c.
      Furthermore, in etoposide-treated P39 cells, no changes in mitochondrial membrane
      potential (delta psi m) were detected by flow cytometry. Flow cytometry using a
      pH-sensitive probe demonstrated that lysosomal pH increased during early
      apoptosis in P39 cells treated with etoposide. A reduction in the ATP level
      preceded the elevation of lysosomal pH. In addition, specific inhibitors of
      vacuolar H+-ATPase induced apoptosis in P39 cells but not in HL60 cells. Although
      etoposide-induced activation of caspase-3 was followed by DNA ladder formation in
      P39 cells, E-64d, an inhibitor of lysosomal thiol proteases, specifically
      suppressed etoposide-induced activation of caspase-3. Western blotting analysis
      provided direct evidence for the involvement of a lysosomal enzyme, cathepsin L.
      These findings indicate that lysosomal dysfunction induced by a reduction in ATP
      results in leakage of lysosomal enzymes into the cytosolic compartment and that
      lysosomal enzyme(s) may be involved in activation of caspase-3 during apoptosis
      in P39 cells treated with etoposide.

PMID- 11306463
TI  - A cyclin D1/cyclin-dependent kinase 4 binding site within the C domain of the
      retinoblastoma protein.
AB  - Phosphorylation of the retinoblastoma protein (Rb) by the cyclin D1/cyclin
      dependent kinase (cdk) 4 complex (cdk4/D1) is a key regulatory step for
      maintaining the orderly progression of the cell cycle. The B domain of Rb
      contains a site that recognizes and binds the LXCXE motif found in D-type
      cyclins. This interaction is important for phosphorylation of Rb by cdk4/D1,
      although in vitro the Rb C domain alone is efficiently phosphorylated by cdk4/D1.
      A mutation in the C domain of Rb, L901Q, has been identified that completely
      abolishes cdk4/D1 phosphorylation of the isolated C domain. By contrast, the
      L901Q mutation has no effect on phosphorylation by either cyclin E/cdk2 or cyclin
      B/cdk1, suggesting that the interaction between L901Q and cdk4/D1 is specific.
      Introduction of the L901Q mutation into Rb containing the A, B, and C domains
      results in phosphorylation becoming predominantly dependent on the LXCXE binding
      region. However, when the LXCXE binding region of Rb is mutated, phosphorylation
      becomes dependent on the L901 site within the C domain. The L901 binding site can
      supplant the LXCXE binding site for the cdk4/D1-dependent phosphorylation of S780
      and S795 but not S807/S811. Despite the limited homology between C domains of Rb,
      p107, and p130, the L901 site is conserved and introduction of the L925Q mutation
      into the isolated C domain of p107 also inhibits phosphorylation by cdk4/D1.
      These data support a model for cdk4/D1 recognizing two independent binding sites
      in Rb and suggests a conservation of this C domain binding motif for cyclin
      D1/cdk4 kinase among the Rb family of proteins.

PMID- 11306464
TI  - Androgen receptor stabilization in recurrent prostate cancer is associated with
      hypersensitivity to low androgen.
AB  - The androgen receptor (AR) is highly expressed in androgen-dependent and
      recurrent prostate cancer (CaP) suggesting it has a role in the growth and
      progression of CaP. Previously proposed mechanisms for AR reactivation in
      recurrent CaP include altered growth factor signaling leading to protein
      phosphorylation and AR mutations that broaden ligand specificity. To further
      establish a role for AR in recurrent CaP, we compared several properties of AR in
      relation to the growth response to low levels of androgens in model systems of
      androgen-dependent and recurrent CaP. AR from all of the tumors and cell lines
      bound [3H]R1881 with similar high affinity (mean Kd, 0.12 nM). In the absence of
      androgen, AR in androgen-dependent LNCaP cells was unstable with a degradation
      half-time (t(1/2)) of 3 h at 37 degrees C. In contrast, AR was 2-4 times more
      stable in recurrent CWR22 tumors (t(1/2), >12 h) and CWR-R1 or LNCaP-C4-2 cell
      lines (t(1/2), 6-7 h) derived from recurrent prostate tumors. In the recurrent
      CWR22 tumor and its CWR-R1 cell line grown in the absence of androgen, AR
      immunostaining was entirely nuclear, whereas under the same conditions AR in
      LNCaP-C4-2 and LNCaP cells was predominantly nuclear but was also detected in the
      cytoplasm. High level expression, increased stability, and nuclear localization
      of AR in recurrent tumor cells were associated with an increased sensitivity to
      the growth-promoting effects of dihydrotestosterone in the femtomolar range. The
      concentration of dihydrotestosterone required for growth stimulation in CWR-R1
      and LNCaP-C4-2 cells was four orders of magnitude lower than that required for
      androgen-dependent LNCaP cells. The results suggest that AR is transcriptionally
      active in recurrent CaP and can increase cell proliferation at the low
      circulating levels of androgen reported in castrated men.

PMID- 11306465
TI  - Increased beta-catenin expression and nuclear translocation accompany cellular
      hyperproliferation in vivo.
AB  - Beta-catenin performs critical roles in development and cellular adhesion. More
      recently, an oncogenic role has been described. In colon cancer, decreased E
      cadherin/beta-catenin association is causally linked to increased beta-catenin
      regulated gene expression and increased cellular division. Whether the same
      pathway is active in native epithelia remains unknown. To address this question,
      we used the transmissible murine colonic hyperplasia model to measure changes in
      beta-catenin abundance, nuclear partitioning, target gene (c-myc and cyclin D1)
      expression, and subcellular distribution. Colonocyte hyperproliferation was
      associated with a 4.3 +/- 0.56 (SD)-fold increase in total cellular beta-catenin
      protein content, whereas modest changes in gamma-catenin and E-cadherin
      expression were recorded. The beta-catenin signal increased before changes in
      mucosal crypt length, a gross index of cellular proliferation/apoptosis. Beta
      catenin detected in Triton X-100-soluble (cytosolic) cellular fractions was
      enriched 4.3 +/- 0.9 (SD)-fold, whereas a modest decrease of 0.9 +/- 0.09 (SD)
      fold was recorded in Triton X-100-insoluble (cytoskeletal) fractions. After these
      changes, nuclear beta-catenin partitioning increased 2.4 +/- 0.4 (SD)-fold,
      accompanied by 2.5 +/- 0.4- and 4.0 +/- 0.8-fold (SD) increases in cellular c-myc
      and cyclin D1 levels, respectively. Thus, increased cellular cytosolic and
      nuclear beta-catenin levels were associated with increased beta-catenin target
      protein expression. Significant alterations in beta-catenin subcellular
      distribution were also recorded immunohistochemically. Apical/lateral junctional
      labeling was observed in normal crypts with increased lateral membrane staining
      within the upper regions. During transmissible murine colonic hyperplasia, these
      gradients were dissipated, and basilar plaques were formed within a subset of
      basal crypt cells. These findings predict that an oncogenic signaling mechanism
      related to non-E-cadherin-bound beta-catenin is active in hyperproliferating
      native colonocytes and is similar to that recorded during the early stages of
      colon carcinogenesis.

PMID- 11306466
TI  - Tumor vascularity: a histological measure of angiogenesis and hypoxia.
AB  - In this study we sought to clarify the relationship between tumor vascularity,
      hypoxia, and angiogenesis in human cervix tumors. Two hypotheses were
      established: first, that measurement of tumor vascularity can provide a
      histological assessment of both hypoxia and angiogenesis; and second, that
      expression of angiogenesis-related proteins will provide a surrogate measure of
      tumor hypoxia. To test the first hypothesis, we studied the prognostic
      significance of tumor vascularity measured as both intercapillary distance (ICD;
      thought to reflect tumor oxygenation) and microvessel density (MVD; the hotspot
      method that provides a histological assessment of tumor angiogenesis). The
      relationship was also examined of tumor hypoxia, measured using an Eppendorf
      needle electrode [percentage of values less than 5 mm Hg (HP5)], with ICD and
      MVD. To test the second hypothesis we examined the relationship between HP5 and
      the expression of angiogenesis-associated proteins [vascular endothelial growth
      factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)]. All
      of the biological measurements were made on pretreatment tumors. Analysis of data
      was carried out using log-rank statistics, Cox multivariate analysis, and
      Spearman's rank correlation. Both ICD and MVD were significant independent
      prognostic factors for local control. Patients with poorly vascularized tumors
      (long ICD) had poor local control (P = 0.042). However, patients with poorly
      vascularized tumors, measured as low MVD, had good local control (P = 0.036). For
      107 patients in whom both of the measurements were obtained on the same tumor
      sections, ICD and MVD provided independent prognostic information in multivariate
      analysis. There was a significant correlation between tumor hypoxia and ICD (P <
      0.005) but not MVD (P = 0.41). There was no relationship between hypoxia and the
      expression of angiogenic factors (VEGF, PD-ECGF). These analyses show that
      measurement of tumor vascularity can provide different biological information
      that is dependent on the method used. It is, therefore, important that studies
      measuring vascularity should include an appropriate definition. There is no
      relationship between hypoxia and angiogenesis in advanced carcinoma of the cervix
      and examining the levels of angiogenic proteins may not have a role in assessing
      hypoxia in cervix cancer.

PMID- 11306467
TI  - Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic
      parameter in the radiotherapy of oropharyngeal cancer.
AB  - Hypoxia has long been recognized as detrimental to the successful treatment of
      malignant tumors with ionizing radiation. Because hypoxia-inducible factor (HIF)
      1alpha plays an essential role in oxygen homeostasis in vitro, we explored the
      predictive potential of this factor in a cohort of 98 patients with squamous cell
      cancer of the oropharynx, who were treated by curative radiation therapy. Ninety
      four % of the primary tumors showed overexpression of HIF-1alpha, relative to the
      surrounding tissue, as determined by immunohistochemistry. The degree of HIF
      1alpha immunoreactivity correlated inversely with both the rate of complete
      remission of the primary tumor (odds ratio, 0.33; P = 0.03) and lymph node
      metastases (odds ratio, 0.34; P = 0.02) as well as with local failure-free
      survival (risk ratio, 2.15; P = 0.006), disease-free survival (risk ratio, 2.01;
      P = 0.008), and overall survival (risk ratio, 2.17; P = 0.002). The multivariate
      analysis revealed the predictive power of HIF-1alpha to be independent of other
      covariables. We conclude that HIF-1alpha is overexpressed in the vast majority of
      patients with squamous cell cancer of the oropharynx and that the degree of
      expression has predictive and prognostic significance in individuals undergoing
      curative radiation therapy.

PMID- 11306468
TI  - Circumventing tamoxifen resistance in breast cancers using antiestrogens that
      induce unique conformational changes in the estrogen receptor.
AB  - Tamoxifen inhibits estrogen receptor (ER) transcriptional activity by
      competitively inhibiting estradiol binding and inducing conformational changes in
      the receptor that may prevent its interaction with coactivators. In bone, the
      cardiovascular system, and some breast tumors, however, tamoxifen exhibits
      agonist activity, suggesting that the tamoxifen-ER complex is not recognized
      identically in all cells. We used phage display to demonstrate that the
      antiestrogen GW5638 induces a unique structural change in the ER. The biological
      significance of this conformational change was revealed in studies that
      demonstrated that tamoxifen-resistant breast tumor explants are not cross
      resistant to GW5638. Because of these properties, this drug is currently being
      developed as a potential therapeutic for tamoxifen-resistant breast cancers.

PMID- 11306469
TI  - Characterization of the biological activity of gamma-glutamyl-Se
      methylselenocysteine: a novel, naturally occurring anticancer agent from garlic.
AB  - Gamma-glutamyl-Se-methylselenocysteine (GGMSC) has recently been identified as
      the major Se compound in natural garlic and selenized garlic. Our working
      hypothesis is that GGMSC serves primarily as a carrier of Se-methylselenocysteine
      (MSC), which has been demonstrated in past research to be a potent cancer
      chemopreventive agent in animal carcinogenesis bioassays. The present study was
      designed to examine the in vivo responses to GGMSC or MSC using a variety of
      biochemical and biological end points, including (a) urinary Se excretion as a
      function of bolus dose; (b) tissue Se accumulation profile; (c) anticancer
      efficacy; and (d) gene expression changes as determined by cDNA array analysis.
      Our results showed that like MSC, GGMSC was well absorbed p.o., with urinary
      excretion as the major route for eliminating excess Se. When fed chronically, the
      profile of Se accumulation in various tissues was very comparable after treatment
      with either GGMSC or MSC. In rats that had been challenged with a carcinogen,
      supplementation with either GGMSC or MSC resulted in a lower prevalence of
      premalignant lesions in the mammary gland, and fewer mammary carcinomas when
      these early lesions were allowed to progress. More importantly, we found that a
      short term GGMSC/MSC treatment schedule of 4 weeks immediately after carcinogen
      dosing was sufficient to provide significant cancer protection, even in the
      absence of a sustained exposure past the initial 4-week period. With the use of
      the Clontech Atlas Rat cDNA Array, we further discovered that the gene expression
      changes induced in mammary epithelial cells of rats that were given either GGMSC
      or MSC showed a high degree of concordance. On the basis of the collective
      biology, biochemistry, and molecular biology data, we conclude that GGMSC is an
      effective anticancer agent with a mechanism of action very similar to that of
      MSC.

PMID- 11306470
TI  - Inhibition of platelet-derived growth factor receptors reduces interstitial
      hypertension and increases transcapillary transport in tumors.
AB  - Most solid malignancies display interstitial hypertension and a poor uptake of
      anticancer drugs. Platelet-derived growth factor (PDGF) and the cognate tyrosine
      kinase receptors are expressed in many tumors. Signaling through PDGFbeta
      receptors was shown recently to increase interstitial fluid pressure (IFP) in
      dermis after anaphylaxis-induced lowering of IFP. In this study, we show that
      treatment with the selective PDGF receptor kinase inhibitor, STI571, formerly
      known as CGP57148B, decreased the interstitial hypertension and increased
      capillary-to-interstitium transport of 51Cr-EDTA in s.c. growing rat PROb colonic
      carcinomas. Furthermore, treatment with an antagonistic PDGF-B oligonucleotide
      aptamer decreased interstitial hypertension in these tumors. PDGFbeta receptors
      were expressed in blood vessels and stromal cells but not in the tumor cells of
      PROb colonic carcinomas. Our study indicates a previously unrecognized role of
      PDGF receptors in tumor biology, although similar effects of PDGF on IFP have
      been demonstrated previously in the dermis. The data suggest interference with
      PDGF receptors, or their ligands, as a novel strategy to increase drug uptake and
      therapeutic effectiveness of cancer chemotherapy.

PMID- 11306471
TI  - Comparative biodistribution and metabolism of carbon-11-labeled N-[2
      (dimethylamino)ethyl]acridine-4-carboxamide and DNA-intercalating analogues.
AB  - The tricyclic carboxamide N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA)
      is a DNA-intercalating agent capable of inhibiting both topoisomerases I and II
      and is currently in Phase II clinical trial. Many related analogues have been
      developed, but despite their potent in vitro cytotoxicities, they exhibit poor
      extravascular distribution. As part of an ongoing drug development program to
      obtain related "minimal intercalators" with lower DNA association constants, we
      have compared the biodistribution and metabolite profiles of the prototype
      compound, DACA, with three analogues to aid rational drug selection. All of these
      compounds share a common structural feature, N-dimethyl side chain, which was
      radiolabeled with the positron-emitting radioisotope, carbon-11. This strategy
      was selected because it allows promising candidates emerging from preclinical
      studies in animals to be evaluated rapidly in humans using positron emission
      tomography (PET). The acridine DACA, the phenazine SN 23490, the pyridoquinoline
      SN 23719, and the dibenzodioxin SN 23935 were found to be cytotoxic in in vitro
      assays with an IC50 of 1.4-1.8 microM, 0.4-0.6 microM, 1.3-1.6 microM, and 24-36
      microM, respectively, in HT29, U87MG, and A375M cell lines. Ex vivo
      biodistribution studies with carbon-11 radiolabeled compounds in mice bearing
      human tumor xenografts showed rapid clearance of 11C-radioactivity (parent drug
      and metabolites) from blood and the major organs. Rapid hepatobiliary clearance
      and renal excretion were also observed. There was low [<5% of injected dose/gram
      (%ID/g)] and variable uptake of 11C-radioactivity in three tumor types for all of
      the compounds. Tumor (U87MG) to blood 11C-radioactivity for [11C]DACA, [11C](9
      methoxyphenazine-1-carboxamide (SN 23490), [11C]2-(4-pyridyl)quinoline-8
      carboxamide (SN 23719), and [11C]dibenzo[1,4]dioxin-1-carboxamide (SN 23935) at
      30 min were 2.9 +/- 1.1, 2.3 +/- 0.6, 2.6 +/- 0.6, and 0.7 +/- 0.2, respectively.
      For SN 23719, the distribution of 11C-radioactivity in normal tissues and tumors
      determined ex vivo was in broad agreement with that determined in vivo by whole
      body PET scanning. [11C]DACA was rapidly and extensively metabolized to several
      plasma metabolites and a major tumor metabolite. In contrast, [11C]SN 23935,
      [11C]SN 23490, and [11C]SN 23719 showed less extensive metabolism. In the tumor
      samples, the parent [11C]DACA and [11C]SN 23935 represented between 0.3 and
      1.5%ID/g, whereas [11C]SN 23490 and [11C]SN 23719 represented between 1.5 and
      2.8%ID/g. In conclusion, by using a strategy with 11C-labeling, we have
      determined the tissue distribution and metabolic stability of novel tricyclic
      carboxamides with the view of selecting analogues with potentially better in vivo
      activity against solid tumors. SN 23490 and SN 23719 had more favorable
      distribution and metabolic stability compared with DACA and SN 23935 and may
      warrant further development. The radiolabeling strategy used allows ex vivo and
      in vivo evaluation of promising anticancer agents in animals and offers the
      potential of rapid translation to studies in humans using PET.

PMID- 11306472
TI  - Inhibition of heat shock protein 90 function by ansamycins causes the
      morphological and functional differentiation of breast cancer cells.
AB  - 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is an ansamycin antibiotic that
      binds to a conserved pocket in Hsp90 and induces the degradation of proteins that
      require this chaperone for conformational maturation. 17-AAG causes a
      retinoblastoma (RB)-dependent G1 block in cancer cells and is now in clinical
      trial. In breast cancer cells, G1 block is accompanied by differentiation and
      followed by apoptosis. The differentiation is characterized by specific changes
      in morphology and induction of milk fat proteins and lipid droplets. In cells
      lacking RB, neither G1 arrest nor differentiation occurs; instead, they undergo
      apoptosis in mitosis. Introduction of RB into these cells restores the
      differentiation response to 17-AAG. Inhibitors of the ras, mitogen-activated
      protein kinase, and phosphatidylinositol 3-kinase pathways cause accumulation of
      milk fat proteins and induction of lipid droplets when associated with G1 arrest
      but do not cause morphological changes. Thus, regulation of Hsp90 function by 17
      AAG in breast cancer cells induces RB-dependent morphological and functional
      mammary differentiation. G1 arrest is sufficient for some but not all aspects of
      the phenotype. Induction of differentiation may be responsible for some of the
      antitumor effects of this drug.

PMID- 11306473
TI  - Fiber knob modifications overcome low, heterogeneous expression of the
      coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and
      oncolysis for human rhabdomyosarcoma cells.
AB  - Exploiting the lytic life cycle of viruses has gained recent attention as an
      anticancer strategy (oncolysis). To explore the utility of adenovirus (Ad)
      mediated oncolysis for rhabdomyosarcoma (RMS), we tested RMS cell lines for Ad
      gene transduction and infection. RMS cells were variably transduced by Ad.
      Compared with control cells, RMS cells were less sensitive or even resistant to
      oncolysis by wild-type virus. RMS cells expressed the Ad internalization
      receptors, alpha(v) integrins, but had low or undetectable expression of the
      major attachment receptor, coxsackievirus-Ad receptor (CAR). Mutant Ads with
      ablated CAR binding exhibited only 5-20% of transgene expression in RMS cells
      seen with a wild-type vector, suggesting that residual or heterogeneous CAR
      expression mediated the little transduction that was detectable.
      Immunohistochemical analysis of archived clinical specimens showed little
      detectable CAR expression in five embryonal and eight alveolar RMS tumors. Stable
      transduction of the cDNA for CAR enabled both efficient Ad gene transfer and
      oncolysis for otherwise resistant RMS cells, suggesting that poor CAR expression
      is the limiting feature. Gene transfer to RMS cells was increased >2 logs using
      Ads engineered with modified fiber knobs containing either an integrin-binding
      RGD peptide or a polylysine peptide in the exposed HI loop. The RGD modification
      enabled increased oncolysis for RMS cells by a conditionally replicative Ad, Ad
      delta24RGD, harboring a retinoblastoma-binding mutation in the E1A gene. Thus,
      the development of replication-competent vectors targeted to cell surface
      receptors other than CAR is critical to advance the use of Ad for treating RMS.

PMID- 11306474
TI  - Unusual potency of BN 80915, a novel fluorinated E-ring modified camptothecin,
      toward human colon carcinoma cells.
AB  - BN 80915 is the lead compound from a novel class of E-ring modified camptothecin
      analogues, the homocamptothecins, which show potent antitumor activities in
      animal models. Here, we report that BN 80915 induces up to 2-fold more cleavable
      complexes between plasmid DNA and purified human topoisomerase I than SN-38 and
      camptothecin. BN 80915 also induces DNA-topoisomerase I complexes in living HT-29
      colon carcinoma cells, as shown by the in vivo link assay. BN 80915 is an
      extremely potent inducer of DNA-protein complexes in these cells starting at a
      concentration of 5 nM in the media. BN 80915 is clearly more potent than SN-38,
      because at least 20 times more SN-38 is needed to induce comparable levels of
      cleavable complexes. Kinetic experiments show that BN 80915 induces cleavable
      complexes within minutes that remain stable for at least 6 h in the presence of
      drug. Whereas the majority of the complexes are reversed within 15 min after drug
      removal, a substantial fraction (30%) persists for at least 4 h, in contrast with
      SN-38-treated cells, where all complexes have disappeared by this time. BN 80915
      shows strong antiproliferative effects toward HT-29 cells with an IC50 of 0.3 nM
      compared with 20 nM for SN-38 and 40 nM for topotecan. BN 80915 is also potent
      against other colon carcinoma cells as well as toward cells growing in three
      dimensions as multicellular spheroids. HL-60 cells expressing functional P
      glycoprotein or multidrug resistance protein show no cross-resistance toward BN
      80915. Taken together, our results show that BN 80915 is unusually potent toward
      human colon carcinoma cells because of the formation of high levels of stable,
      covalent DNA-topoisomerase complexes.

PMID- 11306475
TI  - A novel metastatic animal model reflecting the clinical appearance of human
      neuroblastoma: growth arrest of orthotopic tumors by natural, cytotoxic human
      immunoglobulin M antibodies.
AB  - Neuroblastoma (NB), the most common extracranial solid tumor in childhood is
      associated with poor prognosis in patients with advanced tumor stages. Natural
      human cytotoxic anti-NB IgM antibodies present in the serum of healthy humans are
      discussed as a potential novel immunotherapeutic regimen against human NB because
      these antibodies have been shown to affect growth arrest of solid s.c. xenografts
      of human NB in nude rats. Subcutaneously induced tumors, however, exhibit a
      different growth pattern compared with the typical growth pattern of NB tumors in
      humans. Therefore, we developed in this study a novel metastatic tumor model in
      nude rats that reflects the clinical appearance of human NB and used this model
      to study the therapeutic efficacy of human anti-NB IgM. Intra-aortal injection of
      human NB cells in nude rats resulted in the development of large invasive adrenal
      gland tumors and micrometastases in the liver and bones. Apparently, adrenal
      glands provide most favorable growth conditions for human NB cells, as documented
      by the preferential and rapid growth of NB cells in this location. We studied
      three different treatment protocols of natural human anti-NB IgM. Anti-NB IgM
      completely inhibited tumor formation and metastases when injected simultaneously
      with human LAN-1 NB cells (P < 0.05). When antibody treatment was started 6 days
      after tumor cell injection (i.e., micrometastatic stage), tumor growth was
      inhibited by 90% (P < 0.05). An anti-NB IgM therapy directed against established
      tumors (14 days after tumor cell injection) shrank adrenal gland tumors by 90% (P
      < 0.05). Analysis of the tumors revealed both complement activation and an
      induction of apoptosis as two independent mechanisms of antitumor function. This
      study strongly suggests human anti-NB IgM antibodies as new agents for the
      therapy of neuroblastoma.

PMID- 11306476
TI  - Doppler ultrasound imaging detects changes in tumor perfusion during antivascular
      therapy associated with vascular anatomic alterations.
AB  - Noninvasive monitoring of antiangiogenic therapy was performed by serial power
      Doppler ultrasound imaging of murine tumors treated with recombinant interleukin
      12, the results of which were correlated with assessments of tumor vascularity by
      microscopy. Growth of established K1735 tumors, but not of IFN-gamma-unresponsive
      K1735.N23 variants, was suppressed by treatment. Serial Doppler imaging of K1735
      tumor vascularity during treatment revealed a progressive change from a diffuse
      perfusion pattern to a more punctate distribution. Quantitative analysis of the
      images revealed that color-weighted fractional average, representing overall
      tumor perfusion, consistently decreased in these tumors, primarily because of a
      decrease in fractional tumor cross-sectional area carrying blood flow. In
      contrast, these parameters increased in nonresponsive tumors during treatment.
      Confocal microscopy of thick tumor sections revealed a reduction in the density
      and arborization of vessels labeled in vivo by fluorochrome-conjugated lectin
      with effective treatment. Immunohistological examination of thin tumor sections
      confirmed the preferential loss of small vessels with successful therapy. Similar
      changes in tumor vascular anatomy and perfusion were also observed during
      recombinant interleukin 12 treatment of two other responsive murine tumor types.
      These results indicate that power Doppler ultrasound is a sensitive, noninvasive
      method for reporting functional consequences of therapy-induced vascular
      anatomical changes that can be used to serially monitor tumor perfusion and
      efficacy of antivascular therapy in clinical trials.

PMID- 11306477
TI  - Positron emission tomography-based imaging of transgene expression mediated by
      replication-conditional, oncolytic herpes simplex virus type 1 mutant vectors in
      vivo.
AB  - To evaluate the efficiency of gene delivery in gene therapy strategies for
      malignant brain tumors, it is important to determine the distribution and
      magnitude of transgene expression in target tumor cells over time. Here, we
      assess the time- and vector dose-dependent kinetics of recombinant herpes simplex
      virus (HSV)-1 vector-mediated gene expression and vector replication in culture
      and in vivo by a recently developed radiotracer method for noninvasive imaging of
      gene expression (J. G. Tjuvajev et al., Cancer Res., 55: 6126-6132, 1995). The
      kinetics of viral infection of rat 9L gliosarcoma cells by the replication
      conditional HSV-1 vector, hrR3, was studied by measuring the accumulation rate of
      2-[14C]-fluoro-5-iodo-1-beta-D-arabinofuranosyl-uracil (FIAU), a selective
      substrate for viral thymidine kinase (TK). The level of viral TK activity in 9L
      cells was monitored by the radiotracer assay to assess various vector doses and
      infection times, allowing vector replication and spread. In parallel, viral
      yields and levels of Escherichia coli beta-galactosidase activity were assessed
      quantitatively. To study vector replication, spread and HSV-1-tk and lacZ gene
      coexpression in vivo, first- or second-generation recombinant HSV-1 vectors (hrR3
      or MGH-1) were injected into s.c. growing rat 9L or human U87 deltaEGFR gliomas
      in nude rats at various times (8 h to 8 days) and at various vector doses [1 x
      10(6) to 2 x 10(9) plaque-forming units (PFUs)] prior to imaging. For noninvasive
      assessment of HSV-1-tk gene expression (124I-labeled FIAU % dose/g), 0.15 mCi of
      124I-labeled FIAU was injected i.v. 8 h after the last vector administration, and
      FIAU positron emission tomography (PET) was performed 48 h later. For the
      assessment of HSV-1-tk and lacZ gene coexpression, 0.2 mCi of 131I-labeled FIAU
      was injected i.v. 24 h after the last vector administration. Forty-eight h later,
      animals were killed, and tumors were dissected for quantitative
      autoradiographical and histochemical assessment of regional distribution of
      radioactivity (TK expression measured as 131I-labeled FIAU % dose/g) and
      coexpressed lacZ gene activity. The rates of FIAU accumulation (Ki) in hrR3
      infected 9L cells in culture, which reflect the levels of HSV-1-tk gene
      expression, ranged between 0.12 and 3.4 ml/g/min. They increased in a vector dose
      and infection time-dependent manner and correlated with the virus yield
      (PFUs/ml), where the PFUs:Ki ratios remained relatively constant over time.
      Moreover, a linear relationship was observed between lacZ gene expression and
      FIAU accumulation 5-40 h after infection of 9L cells with a multiplicity of
      infection of 1.5. At later times (> 52 h postinjection), high vector doses
      (multiplicity of infection, 1.5) led to a decrease of FIAU accumulation rates,
      viral yield, and cell pellet weights, indicating vector-mediated cell toxicity.
      Various levels of HSV-1-tk gene expression could be assessed by FIAU-PET after in
      vivo infection of s.c. tumors. The levels of FIAU accumulation were comparatively
      low (approximately ranging from 0.00013 to 0.003% injected dose/g) and were
      spatially localized; this may reflect viral-induced cytolysis of infected tumor
      cells and limited lateral spread of the virus. Image coregistration of tumor
      histology, HSV-1-tk related radioactivity (assessed by autoradiography), and lacZ
      gene expression (assessed by beta-galactosidase staining) demonstrated a
      characteristic pattern of gene expression around the injection sites. A rim of
      lacZ gene expression immediately adjacent to necrotic tumor areas was observed,
      and this zone was surrounded by a narrow band of HSV-1-tk-related radioactivity,
      primarily in viable-appearing tumor tissue. These results demonstrate that
      recombinant HSV-1 vector-mediated HSV-1-tk gene expression can be monitored
      noninvasively by PET, where the areas of FIAU-derived radioactivity identify the
      viable portion of infected tumor tissue that retains FIAU accumulation ability,
      and that the accumulation rate of FIAU in culture, Ki, reflects the number of HSV
      1 viral particles in the infected tumor cell population [4.1 +/- 0.6 x 10(6)
      PFUs/Ki unit (PFUs divided by ml/min/g)]. Moreover, time-dependent and spatial
      relationships of HSV-1-tk and lacZ gene coexpression in culture and in vivo
      indicate the potential for indirect in vivo imaging of therapeutic gene
      expression in tumor tissue infected with any recombinant HSV-1 vector where a
      therapeutic gene is substituted for the lacZ gene.

PMID- 11306478
TI  - Radiosensitization of tumor-targeted radioimmunotherapy with prolonged topotecan
      infusion in human breast cancer xenografts.
AB  - Clinical radioimmunotherapy (RIT) of solid tumors holds great promise, but as yet
      has been unable to deliver tumoricidal radiation doses without unacceptable
      toxicity. Our experimental approach aims to potentiate the therapeutic action of
      radioimmunoconjugates at the tumor site and thus improve the efficacy of RIT by
      combination with other treatment modalities. The topoisomerase I inhibitors are a
      unique class of chemotherapeutic agents that interfere with DNA breakage-reunion
      by inhibiting the action of topoisomerase I. Preclinical studies suggest that
      prolonged infusion of topoisomerase I inhibitors enhances cell toxicity due to
      ionizing radiation. We evaluated the efficacy of combined treatment with
      continuous administration of topotecan and 90Y-MX-DPTA BrE3 monoclonal antibody
      (which recognizes an epitope of breast epithelial mucin expressed in most breast
      cancers) on human mammary carcinoma xenografts in nude mice. Topotecan or 90Y
      BrE3 treatment alone delayed overall tumor growth rate transiently but did not
      affect survival. The combination of RIT with topotecan substantially reduced
      growth of relatively large established tumors and caused complete tumor
      regressions and prolonged tumor-free survival in a substantial proportion of
      treated animals. In vitro studies demonstrated an increase in apoptotic rate and
      a decrease in cell proliferation of tumor cell lines treated with this
      combination. We combined the radiosensitization property of topotecan and the
      specificity of systemic RIT to establish a novel therapy for solid tumors in an
      experimental tumor xenograft model.

PMID- 11306479
TI  - Tamoxifen inhibits nerve growth factor-induced proliferation of the human breast
      cancerous cell line MCF-7.
AB  - An array of polypeptide growth factors contribute to the development of breast
      cancer, the most common tumor-related cause of death in women of Western
      countries. Therefore, breast cancer therapy should be aimed at inhibition of
      growth factor-dependent breast cancerous cell proliferation. However, the
      relative contribution of each individual factor in the development and
      maintenance of the transformed phenotype is largely unknown. Here we report for
      the first time that the proliferative effects of nerve growth factor, (NGF) a
      typical neurotrophin, are similar to those of epidermal growth factor (EGF) and
      insulin-like growth factor II, and are enhanced by 17beta-estradiol in the human
      breast cancer cell line MCF-7. The effect of NGF appeared to be mediated by its
      trkA receptors (trkA(NGFR)), as suggested by the potent inhibition of both MCF-7
      cell proliferation and trkA(NGFR) phosphorylation occurring upon treatment of
      cultures with the selective trkA(NGFR) inhibitor K252a. Surprisingly, the
      antiestrogen drug tamoxifen (TAM) inhibited NGF-induced MCF-7 cell proliferation
      and trkA(NGFR) phosphorylation in a concentration-related fashion. The effect of
      TAM seemed to be estrogen receptor-independent, because the pure estrogen
      receptor antagonist ICI 182.780 was unable to block NGF-induced trkA(NGFR)
      phosphorylation. Our data underline the new emerging role of trkA(NGFR) in breast
      tumor growth, and suggest a related novel therapeutic use of TAM in breast
      cancer.

PMID- 11306480
TI  - Biological purging of breast cancer cells using an attenuated replication
      competent herpes simplex virus in human hematopoietic stem cell transplantation.
AB  - Autologous hematopoietic stem cell transplantation after myelosuppressive
      chemotherapy is used for the treatment of high-risk breast cancer and other solid
      tumors. However, contamination of the autologous graft with tumor cells may
      adversely affect outcomes. Human hematopoietic bone marrow cells are resistant to
      herpes simplex virus type 1 (HSV-1) replication, whereas human breast cancer
      cells are sensitive to HSV-1 cytotoxicity. Therefore, we examined the utility of
      G207, a safe replication-competent multimutated HSV-1 vector, as a biological
      purging agent for breast cancer in the setting of stem cell transplantation. G207
      infection of human bone marrow cells had no effect on the proportion or
      clonogenic capacity of CD34+ cells but did enhance the proliferation of bone
      marrow cells in culture and the proportion of CD14+ and CD38+ cells. On the other
      hand, G207 at a multiplicity of infection of 0.1 was able to purge bone marrow of
      contaminating human breast cancer cells. Because G207 also stimulates the
      proliferation of human hematopoietic cells, it overcomes a limitation of other
      purging methods that result in delayed reconstitution of hematopoiesis. The
      efficient infection of human bone marrow cells in the absence of detected
      toxicity suggests that HSV vectors may also prove useful for gene therapy to
      hematopoietic progenitor cells.

PMID- 11306481
TI  - Gene therapy targeting for hepatocellular carcinoma: selective and enhanced
      suicide gene expression regulated by a hypoxia-inducible enhancer linked to a
      human alpha-fetoprotein promoter.
AB  - We previously reported that the retroviral vector expressing the herpes simplex
      virus-thymidine kinase gene under the control of 0.3-kb human alpha-fetoprotein
      (AFP) gene promoter (AF0.3) provided the cytotoxicity to ganciclovir (GCV) in
      high-AFP-producing human hepatoma cells but not in low-AFP-producing cells.
      Therefore, specific enhancement of AFP promoter activity is likely to be required
      to induce enough cytotoxicity in low-AFP-producing hepatoma cells. In this study,
      we constructed a hybrid promoter, [HRE]AF, in which a 0.4-kb fragment of human
      vascular endothelial growth factor 5'-flanking sequences containing hypoxia
      responsive element (HRE) was fused to AF0.3 promoter. By means of the reporter
      gene transfection assay, hypoxia-inducible transcriptions that were mediated by
      [HRE]AF promoter were detected in low- and non-AFP-producing human hepatoma
      cells, but not in nonhepatoma cells. When the herpes simplex virus-thymidine
      kinase gene controlled by [HRE]AF promoter was transduced into hepatoma and
      nonhepatoma cells by a retroviral vector, the exposure to 1% O2 induced GCV
      cytotoxicity specifically in the hepatoma cells. Moreover, in nude mice bearing
      solid tumor xenografts, only the tumors consisting of the virus-infected hepatoma
      cells gradually disappeared by GCV administration. These results indicate that
      the hypoxia-inducible enhancer of the human vascular endothelial growth factor
      gene, which is directly linked to human AFP promoter, involves selective and
      enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.

PMID- 11306482
TI  - Herpes simplex virus-1 thymidine kinase mutants created by semi-random sequence
      mutagenesis improve prodrug-mediated tumor cell killing.
AB  - Cancer suicide gene therapy affords the prospect of using the most optimal genes
      available because the source of the therapeutic gene is often irrelevant.
      Currently, there are numerous preclinical and clinical trials to develop tumor
      ablative therapies that use viral, yeast, or bacterial genes. One such gene, the
      herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) is widely used as a
      suicide gene in combination with ganciclovir. In the study reported here, a
      restricted set of random sequences (semi-random) was introduced into the active
      site of HSV-1 TK, and the resulting variants were selected on the basis of their
      ability to confer increased ganciclovir or acyclovir sensitivity to Escherichia
      coli. Sequence analysis demonstrated that functional mutants contained three to
      five amino acid substitutions that are unique and novel combinations. On the
      basis of enzyme assay results, three mutants were identified for further analysis
      in vitro. These three mutants conferred substantial increased sensitivity to both
      ganciclovir and acyclovir when compared with IC50s of wild-type TK expressing rat
      C6 glioma cells. One mutant, SR39, was further evaluated in a xenograft tumor
      model in nude mice. Expression of SR39 in tumors was shown to prevent tumor
      growth at prodrug dosages that did not affect wild-type HSV-1 TK-expressing
      tumors. The use of any of these mutants as a suicide gene should provide a more
      effective and safer alternative to wild-type TK, because lower, less
      immunosuppressive doses of ganciclovir will be necessary for tumor ablation, and
      the use of acyclovir may now be possible.

PMID- 11306483
TI  - Characterization of the effect of hyperthermia on nanoparticle extravasation from
      tumor vasculature.
AB  - The efficacy of novel cancer therapeutics can be hampered by inefficient delivery
      of agents to the tumor at effective concentrations. Liposomes have been used as a
      method to overcome some delivery issues and, in combination with hyperthermia,
      have been shown to increase drug delivery to tumors. This study investigates the
      effects of a range of temperatures (34-42 degrees C) and hyperthermia treatment
      scheduling (time between hyperthermia and drug administration as well as between
      consecutive hyperthermia treatments) on the extravasation of nanoparticles (100
      nm liposomes) from tumor microvasculature in a human tumor (SKOV-3 ovarian
      carcinoma) xenograft grown in athymic nude mouse window chambers. Under
      normothermic conditions (34 degrees C) and at 39 degrees C, nanoparticles were
      unable to extravasate into the tumor interstitium. From 40 to 42 degrees C,
      nanoparticle extravasation increased with temperature, reaching maximal
      extravasation at 42 degrees C. Temperatures higher than 42 degrees C led to
      hemorrhage and stasis in tumor vessels. Enhanced nanoparticle extravasation was
      observed several hours after heating, decaying back to baseline at 6 h
      postheating. Reheating (42 degrees C for 1 h) 8 h after an initial heating (42
      degrees C for 1 h) did not result in any increased nanoparticle extravasation,
      indicating development of vascular thermotolerance. The results of this study
      have implications for the application and scheduling of hyperthermia combined
      with other therapeutics (e.g., liposomes, antibodies, and viral vectors) for the
      treatment of cancer.

PMID- 11306484
TI  - 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine
      (101M): a novel sulfonylhydrazine prodrug with broad-spectrum antineoplastic
      activity.
AB  - Our laboratory has synthesized and evaluated the anticancer activity of a number
      of sulfonylhydrazine DNA modifying agents. As a class, these compounds possess
      broad spectrum antitumor activity, demonstrating significant activity against a
      variety of experimental murine tumors, including the P388 and L1210 leukemias,
      B16 melanoma, M109 lung carcinoma, and M5076 reticulum cell sarcoma, as well as
      against the human LX-1 lung carcinoma xenograft. The current report describes the
      activity of a more recently synthesized member of this class, 1,2
      bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M).
      101M was active in mice against the i.p. implanted L1210 leukemia over a wide
      range of doses and produced long-term survivors when administered as a single
      i.p. bolus of 10, 20, 40, 60, or 80 mg/kg, demonstrating a wider margin of safety
      than the nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Curative
      therapy was achieved with doses of 101M that did not produce depression of the
      bone marrow. 101M was also highly effective against the L1210 leukemia when
      administered by the oral route. The ability of 101M to penetrate the blood-brain
      barrier and eradicate leukemia cells in the brain was remarkable (>6 log kill).
      This agent was also curative against L1210 variants resistant to
      cyclophosphamide, BCNU, or melphalan. Mice implanted with the murine C26 colon
      carcinoma were also cured by two injections of 10 or 20 mg/kg of 101M.
      Administration of 101M by two different well-tolerated regimens caused complete
      regression of established human glioblastoma U251 xenografts in 100% of treated
      mice, and significant responses were also obtained with 101M against advanced
      murine M109 lung carcinomas in mice. The broad spectrum of anticancer activity of
      the sulfonylhydrazine prodrug 101M coupled with the wide range of therapeutic
      safety exhibited by this agent, makes 101M particularly attractive for further
      development and clinical evaluation.

PMID- 11306485
TI  - Magnetic resonance pharmacoangiography to detect and predict chemotherapy
      delivery to solid tumors.
AB  - Detection and prediction of drug delivery to the tumor interstitium are of
      critical importance in cancer chemotherapy. Prediction of drug delivery derived
      from standard pharmacokinetic models is frequently inadequate because of the
      complex nature of tumor blood flow and the microenvironment. Although drug
      concentrations can be directly sampled with microdialysis or in biopsy samples,
      we currently lack methods capable of detecting and/or predicting drug delivery to
      tumors noninvasively. In this study, we describe a novel magnetic resonance (MR)
      technique to directly detect the drug, and we present the correlation between
      delivery of drug and the delivery of MR contrast agents to the tumor. Experiments
      were performed with tumor xenografts in severe combined immunodeficient mice.
      Three-dimensional maps of the drug distribution within the tumors were obtained
      with 13C spectroscopic MR imaging with a spatial resolution of 2 x 2 x 2 mm,
      using signals of the 13C-labeled anticancer agent phenylacetate. Three
      dimensional maps of uptake of gadolinium-diethylenetriaminepentaacetic acid
      (GdDTPA) contrast agent were obtained for the same tumors using dynamic MR
      imaging. Experimental data were analyzed for correlation between delivery of the
      drug and the contrast. Histological analysis was performed for excised tumors.
      Experimental data demonstrated a significant spatial correlation (r = 0.59 with P
      < 0.001) between the parameter representing delivery of the contrast to tumor
      interstitium, determined from the kinetic curves of GdDTPA, and integral tissue
      drug concentrations for two different tumor models. The method is designed to
      probe extravasation of the drug molecules from the bloodstream into the tumor
      interstitium. Although therapeutic efficiency of the drug will also depend upon
      drug retention in the tumor and the ability of the molecules to cross cellular
      membranes, inefficient drug transfer from plasma to tissue can be a major
      impediment in achieving effective tumor chemotherapy. The results of this study
      demonstrate that the uptake kinetics of a low molecular weight MR contrast agent
      can be used to predict delivery of drug molecules of similar size to the
      interstitium of solid tumors.

PMID- 11306486
TI  - Use of a modified ornithine decarboxylase promoter to achieve efficient c-MYC- or
      N-MYC-regulated protein expression.
AB  - One of the advantages of viral-directed enzyme prodrug therapy (VDEPT) is its
      potential for tumor-specific cytotoxicity. However, the viruses used to deliver
      cDNAs encoding prodrug-activating enzymes transduce normal cells as well as tumor
      cells, and several approaches to achieve tumor-specific expression of the
      delivered cDNAs are being investigated. One such approach is to regulate
      transcription of the prodrug-activating enzyme with a promoter that is
      preferentially activated by tumor cells. Published data suggest that the most
      promising transcription factor/promoter/enhancer combinations are those activated
      by a tumor-specific transcription factor to retain tumor cell specificity but
      that are equal in strength to nonspecific viral promoters in their ability to up
      regulate target cDNAs. This report identifies MYC-responsive, modified ornithine
      decarboxylase (ODC) promoter/enhancer sequences that up-regulate target protein
      expression in tumor cells overexpressing either N-MYC or c-MYC protein. The most
      efficient of the four constructs assessed contained six additional CACGTG MYC
      binding sites 5' to the endogenous ODC promoter (R6ODC). Reporter assays with
      this chimeric promoter/enhancer regulating expression of chloramphenicol
      acetyltransferase demonstrated 50-250-fold more activity in MYC-expressing cells
      compared with similar assays with promoterless plasmids. The R6ODC regulatory
      sequence was approximately equivalent to the CMV promoter in inducing expression
      of the neomycin resistance gene in c-MYC-expressing SW480 and HT-29 colon
      carcinoma cells and in N-MYC-expressing NB-1691 neuroblastoma cells. The modified
      ODC promoter may, therefore, be useful in achieving tissue-specific expression of
      target proteins in tumor cells that overexpress c- or N-MYC.

PMID- 11306487
TI  - Ribozyme cleavage of telomerase mRNA sensitizes breast epithelial cells to
      inhibitors of topoisomerase.
AB  - Telomerase activity is necessary and sufficient for immortality in many cells and
      hence represents a prime target for antitumor strategies. Here, we show that a
      hammerhead ribozyme cleaves human telomerase (hTERT) mRNA in vitro. Stable
      transfection in clones of the human breast tumor line MCF-7 and the immortal
      breast cell line HBL-100 results in expression of the ribozyme, diminishes the
      abundance of hTERT mRNA, and inhibits telomerase activity. This led to shortened
      telomeres, inhibition of net growth, and induction of apoptosis. In HBL-100 mass
      cultures infected with a ribozyme-expressing adenovirus diminution of hTERT mRNA,
      attenuation of telomerase activity, inhibition of net growth, and induction of
      apoptosis was found as well. Attenuation of telomerase activity increased the
      sensitivity of HBL-100 and MCF-7 clones specifically to inhibitors of
      topoisomerase. Likewise, expression of exogenous telomerase in originally
      telomerase-negative human fibroblasts decreased their sensitivity to
      topoisomerase poisons but not to a number of other cytotoxic drugs. The data
      validate a ribozyme approach for telomerase inhibition therapy in cancer and
      suggest that it might be combined advantageously with topoisomerase-directed
      chemotherapy.

PMID- 11306488
TI  - Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU
      145 prostate cancer cells.
AB  - Apoptosis induction may be a mechanism mediating the anticancer activity of
      selenium. Our earlier work indicated that distinct cell death pathways are likely
      involved in apoptosis induced by the CH3SeH and the hydrogen selenide pools of
      selenium metabolites. To explore the role of caspases in cancer cell apoptosis
      induced by selenium, we examined the involvement of these molecules in the death
      of the DU-145 human prostate carcinoma cells induced by methylseleninic acid
      (MSeA), a novel penultimate precursor of the putative critical anticancer
      metabolite CH3SeH. Sodium selenite, a representative of the genotoxic selenium
      pool, was used as a reference for comparison. The results show that MSeA-induced
      apoptosis was accompanied by the activation of multiple caspases (caspase-3, -7, 
      8, and -9), mitochondrial release of cytochrome c (CC), poly(ADP-ribose)
      polymerase (PARP) cleavage, and DNA fragmentation. In contrast, selenite-induced
      apoptotic DNA fragmentation was observed in the absence of these changes, but was
      associated with the phosphorylation of c-Jun-NH2-terminal kinase 1/2 and p38
      mitogen-activated protein kinase/stress-activated protein kinase 2. A general
      caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone,
      blocked MSeA-induced cleavage of procaspases and PARP, CC release, and DNA
      nucleosomal fragmentation, but did not prevent cell detachment. Furthermore, PARP
      cleavage and caspase activation were confined exclusively to detached cells,
      indicating that MSeA induction of cell detachment was a prerequisite for caspase
      activation and apoptosis execution. This process therefore resembled "anoikis," a
      special mode of apoptosis induction in which adherent cells lose contact with the
      extracellular matrix. Additional experiments with irreversible caspase inhibitors
      show that MSeA-induced anoikis involved caspase-3- and -7-mediated PARP cleavage
      that was initiated by caspase-8 and probably amplified through CC-caspase-9
      activation and a feedback activation loop from caspase-3. Taken together, the
      data support a methyl selenium-specific induction of DU-145 cell apoptosis that
      involves cell detachment as a prerequisite (anoikis) and is executed principally
      through caspase-8 activation and its cross-talk with multiple caspases.

PMID- 11306489
TI  - The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes
      drug resistance in human multiple myeloma cells.
AB  - Human multiple myeloma (MM) is a presently incurable hematological malignancy,
      and novel biologically based therapies are urgently needed. Proteasome inhibitors
      represent a novel potential anticancer therapy. In this study, we demonstrate
      that the proteasome inhibitor PS-341 directly inhibits proliferation and induces
      apoptosis of human MM cell lines and freshly isolated patient MM cells; inhibits
      mitogen-activated protein kinase growth signaling in MM cells; induces apoptosis
      despite induction of p21 and p27 in both p53 wild-type and p53 mutant MM cells;
      overcomes drug resistance; adds to the anti-MM activity of dexamethasone; and
      overcomes the resistance to apoptosis in MM cells conferred by interleukin-6. PS
      341 also inhibits the paracrine growth of human MM cells by decreasing their
      adherence to bone marrow stromal cells (BMSCs) and related nuclear factor kappaB
      dependent induction of interleukin-6 secretion in BMSCs, as well as inhibiting
      proliferation and growth signaling of residual adherent MM cells. These data,
      therefore, demonstrate that PS-341 both acts directly on MM cells and alters
      cellular interactions and cytokine secretion in the BM millieu to inhibit tumor
      cell growth, induce apoptosis, and overcome drug resistance. Given the acceptable
      animal and human toxicity profile of PS-341, these studies provide the framework
      for clinical evaluation of PS-341 to improve outcome for patients with this
      universally fatal hematological malignancy.

PMID- 11306490
TI  - Adoptive transfer enables tumor rejection targeted against a self-antigen without
      the induction of autoimmunity.
AB  - We have previously described a tumor model in which the influenza hemagglutinin
      protein (HA) expressed on the BALB/c-derived MT901 tumor line serves as an
      immunization-dependent tumor rejection antigen in normal syngeneic mice. Although
      the HA antigen in this model is clearly foreign to normal BALB/c mice, many tumor
      antigens recognized by T cells in humans and mice are nonmutated antigens that
      are expressed on normal tissues as well as on the tumor cells, thereby raising
      issues of self-tolerance and autoimmunity in attempts to use such antigens
      therapeutically. To examine these issues, we have applied our tumor model to
      syngeneic mice that broadly express HA at low levels as a "self"-transgene.
      Unlike the situation in normal BALB/c mice, immunization of HA-transgenic mice
      did not result in tumor protection nor did it generate cytotoxic T cell or IgG
      responses against the HA self-antigen. However, if immunization of HA-transgenic
      mice was preceded by adoptive transfer of spleen and lymph node cells from normal
      untreated BALB/c mice, then HA-specific tumor protective immune responses were
      generated. Despite the self-nature of the HA antigen, no obvious manifestations
      of autoimmunity were observed. The immunity established in the transgenic mice
      was notably different from that observed in normal mice in that it was
      considerably more transient and required CD4 T cells for both successful
      immunization and subsequent tumor protection, qualities that were not associated
      with the immunity established in normal BALB/c mice. Collectively our results
      suggest that transferred cells can be transiently and selectively directed
      against a tumor-expressed self-antigen before returning to a tolerant state.

PMID- 11306491
TI  - Fas-induced expression of chemokines in human glioma cells: involvement of
      extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein
      kinase.
AB  - Fas transduces not only apoptotic signals through various pathways but also
      angiogenic and proinflammatory responses in vivo. Human glioma cells express Fas
      although sensitivity to Fas-mediated cell death is variable, suggesting that Fas
      may have functions other than apoptosis in these cells. In this study, we
      addressed alternative functions of Fas expressed on human gliomas by Fas ligation
      in three human glioma cell lines, CRT-MG, U373-MG, and U87-MG, and the in vivo
      expression of Fas and chemokines in human glioblastoma multiforme (GBM). Herein,
      we demonstrate that: (a) stimulation with agonistic anti-Fas monoclonal antibody
      CH-11 and human recombinant soluble Fas ligand induces expression of the CC
      chemokine MCP-1 and the CXC chemokine interleukin-8 by human glioma cell lines at
      the mRNA and protein levels in a dose- and time-dependent manner; (b) selective
      pharmacological inhibitors of MEK1 (U0126 and PD98059) and p38 mitogen-activated
      protein kinase (MAPK) (SB202190) suppress Fas-mediated chemokine expression in a
      dose-dependent manner; (c) Fas ligation on human glioma cells leads to activation
      of both extracellular signal-regulated kinases ERK1/ERK2 and p38 MAPK; and (d)
      GBM samples express higher levels of Fas compared with normal control brain,
      which correlates with increased interleukin 8 expression. These findings indicate
      that Fas ligation on human glioma cells leads to the selective induction of
      chemokine expression, which involves the ERK1/ERK2 and p38 MAPK signaling
      pathways. Therefore, the Fas-Fas ligand system in human brain tumors may be
      involved not only in apoptotic processes but also in the provocation of
      angiogenic and proinflammatory responses.

PMID- 11306492
TI  - Inhibition of caspases maintains the antineoplastic function of gammadelta T
      cells repeatedly challenged with lymphoma cells.
AB  - T lymphocytes recognizing tumor antigens eventually undergo anergy or Fas
      mediated death. V gamma9/V delta2+ T cells recognize poorly characterized ligand
      moieties on human B-cell lymphomas. Here we show that gammadelta T cells, a model
      for the study of activation-induced apoptosis, activate on repeated in vitro
      antigen-recognition caspase 3 and 8 and dramatically down-regulate their
      cytotoxic and secretory function. Caspase hindrance enhanced gammadelta T cell
      survival and sustained the killing of neoplastic cells and the release of IFN
      gamma and tumor necrosis factor alpha. Caspases of tumor-specific T cells
      represent a candidate target to complement adoptive immunotherapy strategies.

PMID- 11306493
TI  - IL-4 prevents the blockade of dendritic cell differentiation induced by tumor
      cells.
AB  - Malignant cells may escape from the immune response in vivo because of a
      defective differentiation of professional antigen-presenting cells (APCs), i.e.,
      dendritic cells (DCs). We recently reported that tumor cells release interleukin
      (IL)-6 and macrophage colony stimulating factor (M-CSF), which inhibit the
      differentiation of CD34+ cells into DCs and promote their commitment toward
      monocytic lineage with a poor APC function. The results presented here show that
      both IL-4 and IL-13 reverse the inhibitory effects of renal cell carcinoma
      conditioned media (RCC CM) or IL-6+M-CSF on the phenotypic and functional
      differentiation of CD34+ into DCs. IL-4 was found to act through a rapid blockade
      of the expression of M-CSF and the IL-6 receptor-transducing chain (gp130), along
      with a decrease of the secondary production of M-CSF, thereby preventing the loss
      of granulocyte macrophage colony stimulating factor (GM-CSF) receptor alpha chain
      expression on differentiating CD34+ cells. Consistent with these observations,
      the differentiation of DCs from monocytes cultured with GM-CSF and IL-4 was also
      impaired by RCC CM, but the minimal inhibitory concentrations of RCC CM were 10
      fold higher than for CD34+ cells. In these conditions, monocytes cultured with GM
      CSF and IL-4 also exhibited profound phenotypic changes (CD14+ D32+ CD86+ HLA-DR+
      CD115(low) CD23(low) CD1a-) and a poor APC function. These alterations were
      overcome in a dose-dependent manner by IL-4 (5-500 IU/ml), although not beyond a
      40% final concentration of RCC CM. The capacity of RCC CM to block DC
      differentiation from monocytes strongly correlated with IL-6 and M-CSF
      concentrations in medium. Taken together, these results demonstrate that IL-4 and
      IL-13 reverse the inhibitory effect of tumor cells on DC differentiation.

PMID- 11306494
TI  - Hypermethylation of the cpG island of Ras association domain family 1A (RASSF1A),
      a putative tumor suppressor gene from the 3p21.3 locus, occurs in a large
      percentage of human breast cancers.
AB  - The human Ras association domain family 1A gene (RASSF1A), recently cloned from
      the lung tumor suppressor locus 3p21.3, was shown to be hypermethylated in
      primary lung tumors, and reexpression of RASSF1A suppressed the growth of lung
      cancer cells (R. Dammann et al., Nat. Genet., 25: 315-319, 2000). In this study,
      we analyzed the expression and possible alterations of RASSF1A in breast cancer.
      In five breast cancer cell lines (MCF7, MDAMB157, MDAMB231, T47D, and ZR75-1),
      the CpG island and promoter of RASSF1A was completely methylated, and
      transcription was silenced. Treatment with the DNA methylation inhibitor 5-aza-2'
      deoxycytidine reactivated the expression of RASSF1A. In 28 of 45 (62%) primary
      mammary carcinomas, the promoter of RASSF1A was highly methylated at its CpG
      sites. Coincident with methylation, the expression level of RASSF1A was lower in
      tumors compared with matching normal tissues. No somatic mutations were found in
      the samples that were unmethylated. The data suggest that hypermethylation of the
      CpG island promoter of RASSF1A may play an important role in breast cancer
      pathogenesis.

PMID- 11306495
TI  - The retinoblastoma gene regulates somatic growth during mouse development.
AB  - Overexpression of the retinoblastoma gene (Rb) in mice leads to the dwarf
      phenotype. To explore the potential mechanism of Rb effects on the somatic
      growth, bitransgenic mice with tetracycline-regulated Rb expression were
      generated, and their phenotypes were compared with those of previously
      established Rb mouse models. By gestational day 12.5, embryos lacking Rb and
      those expressing twice the regular amount of Rb are 15% larger and 10-30%
      smaller, respectively, compared with their wild-type littermates. The dwarf
      phenotype is associated with increased plasma levels of insulin-like growth
      factor-I (IGF-I) but not with growth hormone and glucose concentrations. Down
      regulation of the Rb transgene expression results in a reduction of the IGF-I
      plasma concentrations to normalcy and an increase of somatic growth prenatally
      and postnatally. Consistent with the in vivo results, cells overexpressing Rb
      require higher thresholds of IGF-I to stimulate proliferation. Thus, Rb plays an
      integral role for mouse somatic growth and maintenance during ontogenesis, and
      IGF-I pathway is likely to be a target for such regulation.

PMID- 11306496
TI  - Unusual profile and high prevalence of p53 mutations in esophageal squamous cell
      carcinomas from northern Iran.
AB  - Over 15,000 human tumor p53 mutations have been recorded in the scientific
      literature, including over 700 mutations in esophageal tumors. There are no data
      on p53 mutations in esophageal cancer patients from Iran yet; however, this
      country experiences one of the highest cancer mortality rates in the world for
      esophageal squamous cell carcinomas (ESCCs). The causes of this high cancer
      burden in Iran remain obscure and do not appear to be related to tobacco and
      alcohol consumption, the two major risk factors identified in Europe and North
      America. Because molecular analysis of tumors can provide clues to endogenous or
      environmental factors contributing to high cancer risk, we examined 74 Iranian
      ESCCs for the presence of mutations in exons 5-8 of the p53 gene by PCR and
      direct sequencing. Forty-eight of the 74 tumors (65%) had one or more p53 gene
      point mutations, including 5 patients with two or more mutations and one with a
      tandem mutation in codon 242. Surprisingly, over one-third of the 54 mutations we
      identified were transitions at CpG sites (20 of a total of 54 mutations, or 37%),
      a class of mutation that is significantly less common (16% of mutations) in the
      compilation of ESCC mutations from other countries (chi2 statistic, P < 0.0002),
      whereas transversions, which the literature shows to be common in ESCCs from non
      Iranian patients, were infrequent in the tumors we examined here. Elevated levels
      of cyclooxygenase-2 and inducible nitric oxide synthase were observed in 74 and
      91%, respectively, of tumors from Tehran as determined by immunohistochemistry,
      and high COX-2 expression correlated significantly with the presence of a p53
      mutation in the tumor. Mediators of the inflammatory response in esophageal
      mucosa, perhaps in conjunction with specific dietary or cultural practices in
      Iran, may contribute importantly to the p53 mutation load in Iranian ESCC
      patients.

PMID- 11306497
TI  - Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma,
      and normal tissue examined by oligonucleotide arrays.
AB  - Using an oligonucleotide array containing sequences complementary to
      approximately 3200 full-length human cDNAs and 3400 expressed sequence tags
      (GeneChip, Affymetrix), mRNA expression patterns were probed in 18 colon
      adenocarcinomas and 4 adenomas. Paired normal tissue was available and analyzed
      for each of the tumors. Relatively few changes in transcript expression are
      associated with colon cancer. Nineteen transcripts (0.48% of those detected) had
      at least 4-10.5-fold higher mRNA expression in carcinoma compared with paired
      normal samples, whereas 47 transcripts (1.3% of those detected) had at least 4-38
      fold or lower expression in the tumor tissue compared with the normal samples.
      Some of these differences were confirmed by reverse transcription-PCR. Many of
      these transcripts were already known to be abnormally expressed in neoplastic
      tissue in general, or colon cancer in particular, and several of these
      differences were also observed in premalignant adenoma samples. A two-way
      hierarchical clustering algorithm successfully distinguished adenoma from
      adenocarcinoma and normal tissue, generating a phylogenetic tree that
      appropriately represented the clinical relationship between the three tissue
      types included in the analysis. This supports the concept that genome-wide
      expression profiling may permit a molecular classification of solid tumors.

PMID- 11306498
TI  - Identification of a novel human fibroblast growth factor and characterization of
      its role in oncogenesis.
AB  - The fibroblast growth factor (FGF) family of signaling molecules has been
      implicated in normal developmental and physiological processes, as well as in
      human malignancy. Using a homology-based genomic DNA mining process, we
      identified a human gene encoding a novel member of the FGF family, that we
      designate FGF-20. The FGF-20 cDNA was isolated, and its sequence confirmed the
      gene prediction. FGF-20 is expressed in normal brain, particularly the
      cerebellum, and in some cancer cell lines. Recombinant FGF-20 protein induces DNA
      synthesis in a variety of cell types and is recognized by multiple FGF receptors.
      Ectopic expression of FGF-20 in NIH 3T3 cells renders the cells transformed in
      vitro and tumorigenic in nude mice. These results underscore the utility of
      mining genomic DNA databases and reveal FGF-20 to be a novel oncogene that may
      play a role in human cancer.

PMID- 11306499
TI  - Genetic and clinical features of human pancreatic ductal adenocarcinomas with
      widespread microsatellite instability.
AB  - The incidences of microsatellite instability (MSI) and underlying DNA mismatch
      repair (MMR) defects in pancreatic carcinogenesis have not been well established.
      We analyzed 100 sporadic and 3 hereditary pancreatic ductal adenocarcinomas for
      MSI, and high-frequency MSI (MSI-H) and low-frequency MSI (MSI-L) tumors were
      further analyzed for frameshift mutations of possible target genes and for
      promoter methylation and mutation of DNA MMR genes, including hMLH1, hMSH2,
      hMSH3, and hMSH6 genes. Among the 100 sporadic tumors, 13 (13%) were MSI-H, 13
      (13%) were MSI-L, and 74 (74%) were microsatellite stable (MSS) tumors. All of
      the three hereditary tumors from hereditary nonpolyposis colorectal cancer
      (HNPCC) patients were MSI-H. MSI-H tumors were significantly associated with poor
      differentiation and the presence of wild-type K-RAS and p53 genes. Patients with
      MSI-H tumors had a significantly longer overall survival time than did those with
      MSI-L or MSS tumors (P = 0.0057). Frameshift mutations of hMSH3, hMLH3, BRCA-2,
      TGF-beta type II receptor, and BAX genes were detected in MSI-H tumors.
      Hypermethylation of the hMLH1 promoter was observed in 6 (46%) of the 13 sporadic
      MSI-H tumors but not in any of the 3 hereditary MSI-H tumors or 13 MSI-L tumors.
      All of the 3 HNPCC cases had germ-line hMLH1 mutation accompanied by loss of
      heterogeneity or other mutation in the tumor. Our results suggest that pancreatic
      carcinomas with MSI-H represent a distinctive oncogenic pathway because they
      exhibit peculiar clinical, pathological, and molecular characteristics. Our
      results also suggest the principal involvement of epigenetic or genetic
      inactivation of the hMLH1 gene in the pathogenesis of pancreatic carcinoma with
      MSI-H.

PMID- 11306500
TI  - The alternative reading frame tumor suppressor inhibits growth through p21
      dependent and p21-independent pathways.
AB  - The alternative reading frame (ARF) tumor suppressor mediates growth arrest or
      apoptosis through activation of the p53 tumor suppressor. A prevailing concept is
      that ARF uses p21Cip1/Waf1, a p53-responsive gene and cyclin-dependent kinase
      (Cdk) inhibitor, to block cell cycle progression. Using p21 nullizygous cells, we
      demonstrate that p21 is nonessential for the antiproliferative activity of ARF
      and p53, although it likely governs the arrest through Cdk inactivation when
      present. ARF overexpression in p21-positive and p21-negative mouse embryo
      fibroblasts (MEFs), but not in primary cells lacking p53, induced a biphasic (G1
      and G2) cell cycle arrest. The ARF-induced growth arrest, regardless of p21
      status, coincided with activation of p53 and accumulation of hypophosphorylated
      retinoblastoma protein (retinoblastoma protein). In ARF-arrested p21-positive
      cells, the presence of growth-inhibitory retinoblastoma protein correlated with
      an absence of Cdk2-dependent kinase activity, an increase in p21 association with
      inactive Cdks, and a lack of cyclin A expression. In contrast, p21-/- mouse
      embryo fibroblasts were arrested by ARF despite containing elevated levels of
      cyclin A protein and highly active Cdk2-dependent kinases. These findings provide
      evidence that ARF can block growth through a p21-independent pathway(s) that
      overrides Cdk2 activation.

PMID- 11306501
TI  - Bin1 mediates apoptosis by c-Myc in transformed primary cells.
AB  - The Bin1 gene encodes a c-Myc-interacting adapter protein with tumor suppressor
      and cell death properties. In this study, we offer evidence that Bin1
      participates in a mechanism through which c-Myc activates programmed cell death
      in transformed primary chick or rat cells. Antisense or dominant inhibitory Bin1
      genes did not affect the ability of c-Myc to drive proliferation or
      transformation, but they did reduce the susceptibility of cells to c-Myc-induced
      apoptosis. Protein-protein interaction was implicated, suggesting that Bin1
      mediates a death or death sensitization signal from c-Myc. Our findings offer
      direct support for the "dual signal" model of Myc apoptotic function, based on
      interactions with a binding protein. Loss of Bin1 in human tumors may promote
      malignant progression in part by helping to stanch the death penalty associated
      with c-Myc activation.

PMID- 11306502
TI  - p53 and p21waf-1 expression correlates with apoptosis or cell survival in poorly
      differentiated, but not well-differentiated, retinoblastomas.
AB  - In human retinoblastomas, rare genetic mutations of the retinoblastoma gene cause
      massive cell proliferation, altered differentiation, and tumor formation; but
      paradoxically, this is accompanied by extensive apoptotic cell loss. We
      quantified the immunohistochemical distribution of p53, its downstream effector
      p21 (WAF-1), and apoptotic cells in 50 human retinoblastomas, within three
      concentric zones of sleeves of tumor cells surrounding blood vessels. In poorly
      differentiated retinoblastomas, both p53 expression and apoptosis increase toward
      the outer zone of tumor sleeves, whereas p21 expression occurs primarily within
      the inner zone. This staining pattern of p53 expression is reversed in well
      differentiated tumors, whereas p21 staining and apoptotic cell distributions are
      unchanged. We detected no p53 mutations in four retinoblastomas and two
      retinoblastoma cell lines. We postulate that oxygen and cell "survival/growth
      factors" delivered via blood vessels protect retinoblastoma cells from apoptosis.
      In poorly differentiated tumors, apoptosis is spatially associated with increased
      p53 expression and may be p53 mediated, but in well-differentiated tumors,
      apoptosis does not colocalize with p53 and may be p53 independent. In
      retinoblastomas, p21 is involved not in cell death by apoptosis but in cell
      survival. Thus, p53 varies its expression (and by implication its function) with
      altered differentiation in retinoblastomas.

PMID- 11306503
TI  - Genomic alterations in malignant transformation of Barrett's esophagus.
AB  - The incidence of adenocarcinoma in Barrett's esophagus has been increasing
      rapidly over the past decades. Neoplastic progression is characterized by three
      well-defined premalignant stages: metaplasia, low-grade dysplasia, and high-grade
      dysplasia. A genome-wide overview, based on comparative genomic hybridization,
      was performed, evaluating 30 Barrett's adenocarcinomas and 25 adjacent
      precursors, i.e., 6 metaplasias, 9 low-grade dysplasias, and 10 high-grade
      dysplasias. The frequency of losses and gains significantly increased in the
      subsequent stages of malignant transformation. Losses of 5q21-q23, 9p21, 17p12
      13.1, 18q21, and Y were revealed in low-grade dysplasias. This was followed by
      loss of 7q33-q35 and gains of 7p12-p15, 7q21-q22, and 17q21 in high-grade
      dysplasias along with high-level amplification (HLA) of 7q21 and 17q21. In the
      invasive cancers, additional losses of 3p14-p21, 4p, 4q, 8p21, 13q14-q31, 14q24.3
      q31, 16q21-q22, and 22q as well as gains of 3q25-q27, 8q23-24.1, 12p11.2-12,
      15q22-q24, and 20q11.2-q13.1 were distinguished along with HLAs of 8p12-p22 and
      20q11.2-q13.1. Approximately one-third of the alterations in the dysplasias were
      also found in the adjacent adenocarcinomas, illustrating that multiple clonal
      lineages can be present in Barrett's esophagus. Novel findings include loss on
      7q, gain on 12p, and the observation of several HLAs in high-grade dysplasias.
      Furthermore, loss of 7q33-q35 was found to represent a significant distinction
      between low-grade and high-grade dysplasia (P = 0.01), whereas loss of 16q21-q22
      and gain of 20q11.2-q13.1 were disclosed to significantly discriminate between
      high-grade dysplasia and adenocarcinoma (P = 0.02 and P = 0.03, respectively).
      This inventory of genetic aberrations increases our understanding of malignant
      transformation in Barrett's esophagus and might provide useful biomarkers for
      disease progression.

PMID- 11306504
TI  - Characterization of molecular abnormalities in human fibroblastic neoplasms: a
      model for genotype-phenotype association in soft tissue tumors.
AB  - Desmoid tumors and fibrosarcomas (FS) are part of a wide spectrum of disordered
      fibroblastic growth that display striking clinical and phenotypic differences.
      This study was designed to characterize molecular abnormalities that are
      associated with these differences and to determine their clinical relevance. A
      cohort of 24 desmoid tumors and 25 low-grade (LG) and 14 high-grade (HG) FS that
      were clinically and pathologically well characterized was analyzed for
      alterations in expression of Ki-67, Bcl-2, retinoblastoma gene product (pRB), and
      p53 by immunohistochemistry. LG-FS and HG-FS showed abnormal expression of Ki-67
      (32 versus 86%), Bcl-2 (48 versus 57%), and pRB (56 versus 93%). In contrast,
      desmoid tumors showed a normal phenotype with these markers. p53 overexpression
      was identified in 20% of LG-FS and in 29% of HG-FS cases but only in 4% of
      desmoid tumors. There was an increasing trend in the proportion of abnormal
      expression of Ki-67, Bcl-2, pRB, and p53 with the increase of tumor
      aggressiveness from desmoid tumors to LG-FS to HG-FS. The molecular differences
      between tumor entities were highly statistically significant (P < 0.01).
      Significant associations between abnormal expression of pRB and recurrence-free
      survival of LG-FS patients (P = 0.05) and between Ki-67 overexpression and
      recurrence-free survival for tumors of >5 cm were observed (P = 0.02). The
      demonstrated differences of molecular alterations in HG-FS, LG-FS, and desmoids
      appear to be related to biological aggressiveness of such tumors, and they might
      be useful to differentiate between histologically similar cases of desmoid tumors
      and LG-FS. pRB and Ki-67 status may be useful to predict recurrence in certain
      subsets of patients.

PMID- 11306505
TI  - Expression profiling suggested a regulatory role of liver-enriched transcription
      factors in human hepatocellular carcinoma.
AB  - By using a cDNA array representing 14,000 cDNA clusters, we studied the
      expression profiles in paired clinical hepatocellular carcinoma (HCC) samples and
      the distal nontumorous liver tissues from the same patients. Despite the
      significant heterogeneity among the clinical samples, 72 genes (including 30
      novel genes) were down-regulated and 84 genes (including 48 novel genes) were up
      regulated in >50% of the cancer samples that were identified. The alterations in
      gene expression levels were confirmed by Northern blot and reverse-transcription
      PCR in all of 4 randomly selected genes. It was conspicuous that 21 of 38
      hepatocarcinoma (HCC) down-regulated genes studied previously were reportedly
      regulated by a group of liver-enriched transcription factors (LETFs), and 12 of
      36 HCC up-regulated genes studied previously were involved in protein
      translation. Reexamination of the cDNA array data further revealed that most of
      the genes known to be regulated by LETFs were down-regulated in at least a
      portion of the HCC samples. Among the LETFs, the expression level of
      CCAAT/enhancer-binding protein (C/EBP) alpha was down-regulated in cancer,
      whereas hepatocyte nuclear factor 1 (HNF-1), HNF-3beta, HNF-4alpha, and HNF
      4gamma were up-regulated. The expression profiling thus suggested multiple
      regulatory pathways involved in HCC, especially that related to LETFs.

PMID- 11306506
TI  - Nitric oxide synthase II gene disruption: implications for tumor growth and
      vascular endothelial growth factor production.
AB  - The expression of a primary initiator of tumor angiogenic responses, vascular
      endothelial growth factor (VEGF), may be induced by nitric oxide (NO) in
      carcinoma cells. However, the net impact of NO on carcinogenesis remains unclear,
      because manipulation of NO levels has been shown to either stimulate or inhibit
      tumor growth. We have investigated the relationship between inducible NO synthase
      (NOS II), VEGF expression, and growth of B16-F1 melanoma over 14 days in wild
      type (NOS II+/+) mice and in those in which the gene for NOS II has been deleted
      (NOS II-/-). B16-F1 tumor growth was measured as wet weight of the excised
      tissue. Tumor NOS II and VEGF localization were evaluated by
      immunohistochemistry, and VEGF mRNA levels were measured by Northern blot
      analysis. In NOS II+/+ mice inoculated with B16-F1 melanoma cells, macroscopic
      tumors were always observed at 14 days; however, 22% of NOS II-/- mice had no
      detectable tumor mass. Immunoreactive NOS II was detected in tumor cells of
      tumors grown in NOS II+/+ but not in NOS II-/- mice. Although immunoreactive VEGF
      was detected in the granules of tumor-associated mast cells from both NOS II+/+
      and NOS II-/- mice, VEGF mRNA expression in tumors from NOS II-/- was half that
      in NOS II+/+ mice. Neither NOS II inhibition, exogenous NO, nor peroxynitrite
      influenced DNA synthesis in culture B16-F1 melanoma cells. The NO donor did not
      alter either VEGF mRNA levels or degranulation in cultures of the mast cell line
      RBL-2H3, but peroxynitrite increased both VEGF mRNA expression and degranulation.
      We conclude that host expression of NOS II contributes to induction of NOS II in
      the tumor and to melanoma growth in vivo, possibly by regulating the amount and
      availability of VEGF.

PMID- 11306507
TI  - Overexpression of CDC25B overrides radiation-induced G2-M arrest and results in
      increased apoptosis in esophageal cancer cells.
AB  - CDC25B phosphatase plays a key role in controlling G2-M progression by
      dephosphorylating two inhibitory residues of CDC2 and also has been suggested to
      have an oncogenic property. In this study, we investigated the effect of CDC25B
      overexpression on radiation-induced G2-M arrest and radiation sensitivity in
      esophageal cancer cells. TE8-CDC25B, in which CDC25B was overexpressed under an
      inducible system, was more radiosensitive than the vector control (TE8-neo) in a
      clonogenic survival assay. Without radiation, CDC25B overexpression had little
      effect on cell cycle fractions or growth rate. After 10-Gy radiation, TE8-CDC25B
      showed decreased G2-M arrest and increased apoptosis, whereas TE8-neo displayed
      prolonged G2-M arrest and less apoptosis. During this period, there were no
      differences in the protein amounts of CDC2 and cyclin B1 between the two cell
      lines. However, more CDC25B expression, which was reduced immediately by
      radiation, was sustained in TE8-CDC25B than in TE8-neo. Moreover, induction of
      tyrosine phosphorylation of CDC2 and reduction of CDC2 kinase activity after
      irradiation was less significant in TE8-CDC25B than in TE8-neo. These results
      indicate that cancer cells that overexpress CDC25B override G2-M arrest by
      retaining CDC2 kinase activity and undergo apoptosis after radiation. This may
      point to an effective approach toward improving radiotherapy outcomes of various
      cancers.

PMID- 11306508
TI  - Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP
      dependent invasion in ovarian cancer cells.
AB  - Ovarian cancer is an highly metastatic disease characterized by ascites formation
      and diffuse i.p. adhesion, invasion, and metastasis. Levels of lysophosphatidic
      acid (LPA) are elevated in the plasma of patients with ovarian carcinoma,
      including 90% of patients with stage I disease, suggesting that LPA may promote
      early events in ovarian carcinoma dissemination. Expression of matrix
      metalloproteinases (MMPs) is also up-regulated in ovarian cancer tissues and
      ascites, and numerous studies have provided evidence for a direct role of MMPs in
      i.p. invasion and metastasis. Using three-dimensional type I collagen cultures or
      immobilized beta1 integrin subunit-specific antibodies, we previously
      demonstrated that beta1 integrin clustering promotes activation of proMMP-2 and
      processing of membrane type 1 MMP in ovarian cancer cells (S. M. Ellerbroek et
      al., Cancer Res., 59: 1635-1641, 1999). In the current study, the effect of LPA
      on MMP expression and invasive activity was investigated. Treatment of ovarian
      cancer cells with pathophysiological levels of LPA increased cellular adhesion to
      type I collagen and beta1 integrin expression. A significant up-regulation of MMP
      dependent proMMP-2 activation was observed in LPA-treated cells, leading to
      enhanced pericellular MMP activity. As a result of increased MMP activity,
      haptotactic and chemotactic motility, in vitro wound closure, and invasion of a
      synthetic basement membrane were enhanced. These data indicate that LPA
      contributes to metastatic dissemination of ovarian cancer cells via up-regulation
      of MMP activity and subsequent downstream changes in MMP-dependent migratory and
      invasive behavior.

PMID- 11306509
TI  - Notch signaling induces cell cycle arrest in small cell lung cancer cells.
AB  - Among the various forms of human lung cancer, small cell lung cancer (SCLC)
      exhibits a characteristic neuroendocrine (NE) phenotype. Neural and NE
      differentiation in SCLC depend, in part, on the action of the basic-helix-loop
      helix (bHLH) transcription factor human achaete-scute homologue-1 (hASH1). In
      nervous system development, the Notch signaling pathway is a critical negative
      regulator of bHLH factors, including hASH1, controlling cell fate commitment and
      differentiation. To characterize Notch pathway function in SCLC, we explored the
      consequences of constitutively active Notch signaling in cultured SCLC cells.
      Recombinant adenoviruses were used to overexpress active forms of Notch1, Notch2,
      or the Notch effector protein human hairy enhancer of split-1 (HES1) in DMS53 and
      NCI-H209 SCLC cells. Notch proteins, but not HES1 or control adenoviruses, caused
      a profound growth arrest, associated with a G1 cell cycle block. We found up
      regulation of p21(waf1/cip1) and p27kip1 in concert with the cell cycle changes.
      Active Notch proteins also led to dramatic reduction in hASH1 expression, as well
      as marked activation of phosphorylated extracellular signal-regulated kinase
      (ERK)1 and ERK2, findings that have been shown to be associated with cell cycle
      arrest in SCLC cells. These data suggest that the previously described function
      of Notch proteins as proto-oncogenes is highly context-dependent. Notch
      activation, in the setting of a highly proliferative hASH1-dependent NE neoplasm,
      can be associated with growth arrest and apparent reduction in neoplastic
      potential.

PMID- 11306510
TI  - Vascular endothelial growth factor-B and vascular endothelial growth factor-C
      expression in renal cell carcinomas: regulation by the von Hippel-Lindau gene and
      hypoxia.
AB  - Angiogenesis is essential for tumor growth and metastasis. It is regulated by
      numerous angiogenic factors, one of the most important being vascular endothelial
      growth factor (VEGF). Recently VEGF-B and VEGF-C, two new VEGF family members,
      have been identified that bind to the tyrosine kinase receptors flt-1 (VEGFR1),
      KDR (VEGFR2), and flt-4 (VEGFR3). Although the importance of VEGF-A has been
      shown in renal carcinomas, the contribution of these new ligands in kidney tumors
      is not clear. We have, therefore, measured the mRNA level of VEGF-B and VEGF-C
      together with their receptors by RNase protection assay (RPA) in 26 normal kidney
      samples and 45 renal cell cancers. We observed a significant up-regulation of
      VEGF-B (P = 0.002) but not VEGF-C (P = 0.3) in neoplastic kidney compared with
      normal tissues. In addition, although VEGF receptors were higher in tumors than
      normal kidney, there was a significant up-regulation of only flt-1 (P = 0.003)
      but not KDR (P = 0.12) or flt-4 (P = 0.09). There was also a significant
      correlation between VEGF-C and both of its receptors flt-4 (P = 0.006) and KDR (P
      = 0.03) but no association between VEGF-B and its receptor flt-1 (P = 0.23). A
      significant increase was observed in flt-1 (P < 0.001), KDR (P = 0.02), and flt-4
      (P = 0.01) but not VEGF-B (P = 0.82) or VEGF-C (P = 0.52) expression in clear
      cell compared with chromophil (papillary) carcinomas. No significant association
      was demonstrated between VEGF-B, VEGF-C, flt-1, KDR, and flt-4 with patient sex,
      patient age, or tumor size (P > 0.05). The effect of von Hippel-Lindau (VHL) gene
      and hypoxia on VEGF-B and VEGF-C expression in the renal carcinoma cell line 786
      0 transfected with wild-type and mutant VHL was determined by growing cells under
      21% O2- and 0.1% O2. In wild-type VHL cells, whereas VEGF-A was significantly up
      regulated under hypoxic compared with normoxic conditions (P < 0.001), expression
      of VEGF-C was reduced (P < 0.002). Nevertheless, the repression of VEGF-C was
      lost in mutant VHL cell lines under hypoxia. In contrast VEGF-B was not regulated
      by VHL despite clear up-regulation in vivo. These findings strongly support an
      enhanced role for this pathway in clear cell carcinomas by regulating
      angiogenesis and/or lymphangiogenesis. The study shows that clear cell tumors are
      able to up-regulate angiogenic growth factor receptors more efficiently than
      chromophil (papillary), that clear cell tumors can use pathways independent of
      VHL to regulate angiogenesis, and that this combined regulation may account for
      their more aggressive phenotype, which suggests that targeting VEGFR1 (flt-l) may
      be particularly effective in these tumor types.

PMID- 11306511
TI  - Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive
      breast cancer.
AB  - mdm2 is part of a complex mechanism that regulates the expression of p53 as well
      as the function of Rb, p19ARF, and other genes. In humans, mdm2 dysregulation is
      associated with gene amplification. This study was undertaken to characterize
      altered mdm2 expression in a cohort of 38 invasive breast cancers and 9 normal
      breast specimens. Reverse-transcription PCR with primers spanning the entire open
      reading frame of the mdm2 gene in breast tissue RNA samples generated PCR
      products of full-length mdm2 (1526 bp) as well as smaller products (653, 281,
      254, and 219 bp). Sequence analysis demonstrated that the 653-bp product was an
      alternatively spliced product (defined as splicing at the exon/intron boundary
      consensus sites), whereas the 281, 254, and 219 bp mdm2 products were aberrantly
      spliced products (splicing at sites not considered to be exon/intron boundary
      sites). Reverse-transcription-PCR with normal breast tissue RNA samples yielded
      only the 1526-bp product in five samples and the 1526-bp product and the 653-bp
      product in four samples. The 653-bp alternatively spliced product was expressed
      in 21% of breast cancers, and the smaller, aberrantly spliced mRNA products (281
      bp, 254 bp, and/or 219 bp) were expressed in 16% of breast cancers. The protein
      products predicted by the alternatively spliced mRNAs and the aberrantly spliced
      mRNAs lacked either the entire binding domain for p53 or the majority of the
      binding domain for p53. Immunohistochemical analysis of HER2/neu (c-erbB2),
      estrogen receptor, progesterone receptor, epidermal growth factor receptor, and
      p53 protein was performed. p53 sequence alterations were identified by mismatch
      detection and confirmed by p53 oligonucleotide microarray technology. An
      association was demonstrated between the expression of aberrantly and/or
      alternatively spliced mdm2 mRNAs and a lack of progesterone receptor. An
      association was also demonstrated between mdm2 aberrantly and/or alternatively
      expression products and the presence of p53 tumor suppressor gene mutations. mdm2
      is transcribed from two different promoters: one, p53-dependent, and the other,
      p53-independent. The 5' untranslated region of the transcripts was evaluated to
      determine the promoter usage in each breast cancer specimen. No correlation was
      observed between mdm2 splice products and promoter usage. The presence of
      aberrant expression products of mdm2 in breast cancer specimens was correlated
      with a shortened overall patient survival. These observations suggest that mdm2
      expression is altered in invasive breast cancer and is associated with more
      aggressive disease.

PMID- 11306513
TI  - Role of vascular endothelial growth factor in the stimulation of cellular
      invasion and signaling of breast cancer cells.
AB  - The expression of vascular endothelial growth factor (VEGF) by breast tumors has
      been previously correlated with a poor prognosis in the pathogenesis of breast
      cancer. Furthermore, VEGF secretion is a prerequisite for tumor development.
      Although most of the effects of VEGF have been shown to be attributable to the
      stimulation of endothelial cells, we present evidence here that breast tumor
      cells are capable of responding to VEGF. We show that VEGF stimulation of T-47D
      breast cancer cells leads to changes in cellular signaling and invasion. VEGF
      increases the cellular invasion of T-47D breast cancer cells on Matrigel/
      fibronectin-coated transwell membranes by a factor of two. Northern analysis for
      the expression of the known VEGF receptors shows the presence of moderate levels
      of Flt-1 and low levels of Flk-1/KDR mRNAs in a variety of breast cancer cell
      lines. T-47D breast cancer cells bind 125I-labeled VEGF with a Kd of 13 x 10(-9)
      M. VEGF induces the activation of the extracellular regulated kinases 1,2 as well
      as activation of phosphatidylinositol 3'-kinase, Akt, and Forkhead receptor L1.
      These findings in T-47D breast cancer cells strongly suggest an autocrine role
      for VEGF contributing to the tumorigenic phenotype.

PMID- 11306514
TI  - Activation of c-Jun NH2-terminal kinase/stress-activated protein kinase
      (JNK/SAPK) is critical for hypoxia-induced apoptosis of human malignant melanoma.
AB  - Mitogen-activated protein kinase (MAPK) signaling was examined in malignant
      melanoma cells exposed to hypoxia. Here we demonstrate that hypoxia induced a
      strong activation of the c-Jun NH2-terminal kinase (JNK), also termed stress
      activated protein kinase (SAPK), in the melanoma cell line 530 in vitro. Other
      members of the MAPK family, e.g., extracellular signal-regulated kinase and p38,
      remained unaffected by the hypoxic stimulus. Activated JNK/SAPK could also be
      observed in the vicinity of hypoxic tumor areas in melanoma metastases as
      detected by immunohistochemistry. Functional analysis of JNK/SAPK activation in
      the melanoma cell line 530 revealed that activation of JNK/SAPK is involved in
      hypoxia-mediated tumor cell apoptosis. Both a dominant negative mutant of
      JNK/SAPK (SAPKbeta K-->R) and a dominant negative mutant of the immediate
      upstream activator of JNK/SAPK, SEK1 (SEK1 K-->R), inhibited hypoxia-induced
      apoptosis in transient transfection studies. In contrast, overexpression of the
      wild-type kinases had a slight proapoptotic effect. Inhibition of extracellular
      signal-regulated kinase and p38 pathways by the chemical inhibitors PD98058 and
      SB203580, respectively, had no effect on hypoxiainduced apoptosis. Under normoxic
      conditions, no influence on apoptosis regulation was observed after inhibition of
      all three MAPK pathways. In contrast to recent findings, JNK/SAPK activation did
      not correlate with Fas or Fas ligand (FasL) expression, suggesting that the
      Fas/FasL system is not involved in hypoxia-induced apoptosis in melanoma cells.
      Taken together, our data demonstrate that hypoxia-induced JNK/SAPK activation
      appears to play a critical role in apoptosis regulation of melanoma cells in
      vitro and in vivo, independent of the Fas/FasL system.

PMID- 11306515
TI  - Apoptotic signaling during initiation of detachment-induced apoptosis ("anoikis")
      of primary human intestinal epithelial cells.
AB  - Apoptosis after the loss of cell anchorage--"anoikis"--plays an important role in
      the life cycle of adherent cells. Furthermore, loss of anchorage dependency is
      believed to be a critical step in metastatic transformation. The aim of this
      study was to further characterize the sequence of intracellular events during
      anoikis in a nontransformed population of human intestinal epithelial cells
      (IECs). Purified human IECs were kept in suspension to induce anoikis in over 90%
      of IECs within 3 h. Two initiator caspases, caspase-2 and -9, are activated
      within 15 min, followed by the hierarchical activation of downstream caspases
      within 1 h. The activation of the caspase FLICE (caspase-8) does not contribute
      to the initiation of anoikis, and massive release of cytochrome c from
      mitochondria cannot be detected before 60 min, indicating that cytochrome c
      release does not play a role during initiation of anoikis. This study delineates
      the signaling cascade during anoikis of nontransformed cells. Future studies may
      identify alterations of this cascade in neoplastic cells, thereby possibly
      gaining insight into carcinogenesis and metastatic transformation.

PMID- 11306516
TI  - Signaling mediated by the closely related mammalian Rho family GTPases TC10 and
      Cdc42 suggests distinct functional pathways.
AB  - The mammalian Rho family GTPases TC10 and Cdc42 share many properties. Activated
      forms of both proteins stimulate transcription mediated by nuclear factor kappaB,
      serum response factor, and the cyclin D1 promoter; activate c-Jun NH2-terminal
      kinase; cooperate with activated Raf to transform NIH-3T3 cells; and, by a
      mechanism independent of all of these effects, induce filopodia formation. In
      contrast, previously reported differences between TC10 and Cdc42 are not
      striking. We now present studies of TC10 and Cdc42 in cell culture that reveal
      clear functional differences: (a) wild-type TC10 localizes predominantly to the
      plasma membrane and less extensively to a perinuclear membranous compartment,
      whereas wild-type Cdc42 localizes predominantly to this compartment and less
      extensively to the plasma membrane; (b) expression of Rho guanine nucleotide
      dissociation inhibitor alpha results in a redistribution of wild-type Cdc42 to
      the cytosol but has no effect on the plasma membrane localization of wild-type
      TC10; (c) TC10 fails to rescue a Saccharomyces cerevisiae cdc42 mutation, unlike
      mammalian Cdc42; (d) dominant negative Cdc42, but not dominant negative TC10,
      inhibits neurite outgrowth in PC12 cells stimulated by nerve growth factor; and
      (e) activation of nuclear factor kappaB-dependent transcription by Cdc42, but not
      by TC10, is inhibited by sodium salicylate. These findings point to distinct
      pathways in which TC10 and Cdc42 may act and distinct modes of regulation of
      these proteins.

PMID- 11306517
TI  - Interleukin-9 (IL-9) induces cell growth arrest associated with sustained signal
      transducer and activator of transcription activation in lymphoma cells
      overexpressing the IL-9 receptor.
AB  - Murine interleukin (IL)-9 inhibits apoptosis in murine T lymphomas via signal
      transducer and activator of transcription (STAT) factors. After transfection of
      the human IL-9 receptor, human IL-9 had a similar antiapoptotic activity, but,
      unlike the mouse protein, inhibited proliferation. This effect was correlated
      with the level of receptor expression and the extent of STAT phosphorylation.
      Expression of a moderate level of suppressor of cytokine signaling 3 (SOCS3)
      reduced STAT activation by human IL-9 and prevented inhibition of growth but not
      of apoptosis. Using mutated IL-9 receptors, we showed that inhibition of
      proliferation was correlated with STAT1 and STAT3 activation by IL-9 and
      induction of the cell cycle inhibitor p19/ink4d, a STAT3 target gene. Activation
      of STAT1 by IFN-gamma did not result in cell growth arrest. In this model, cell
      growth inhibition is therefore associated with a higher number of receptors, a
      more robust STAT activation, and a greater sensitivity to SOCS3 expression,
      compared to apoptosis inhibition.

PMID- 11306518
TI  - Measuring circulating oxidized low-density lipoprotein to evaluate coronary risk.

PMID- 11306519
TI  - Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high
      sensitive C-reactive protein levels.
AB  - BACKGROUND: Prospective studies indicate that baseline levels of C-reactive
      protein (CRP), the prototypic marker of inflammation, are associated with an
      increased risk for cardiovascular events. Limited studies have examined therapies
      that influence high-sensitive CRP (hs-CRP) levels, especially in hyperlipidemic
      patients. Thus, we tested the effects of 3 hydroxymethyl glutaryl coenzyme A
      reductase inhibitors (statins), simvastatin (20 mg/d), pravastatin (40 mg/d), and
      atorvastatin (10 mg/d), on levels of hs-CRP in a randomized, double-blind,
      crossover trial of 22 patients with combined hyperlipidemia (LDL cholesterol >130
      mg/dL and triglycerides of 200 to 600 mg/dL). METHODS AND RESULTS: After 6 weeks
      of an American Heart Association Step 1 diet, fasting blood samples were drawn at
      baseline and after 6 weeks of therapy with each drug. hs-CRP levels were
      significantly decreased after treatment with all 3 statins compared with baseline
      (median values: baseline, 2.6 mg/L; atorvastatin, 1.7 mg/L; simvastatin, 1.7
      mg/L; and pravastatin, 1.9 mg/L; P<0.025). The reductions obtained with the 3
      statins were similar. In addition, there was no significant effect on either
      plasma interleukin-6 or interleukin-6 soluble receptor levels. There was no
      relationship between reductions in hs-CRP and LDL cholesterol. CONCLUSIONS:
      Pravastatin, simvastatin, and atorvastatin significantly decreased levels of hs
      CRP. These data support an anti-inflammatory effect of these drugs.

PMID- 11306520
TI  - Impaired coronary tissue plasminogen activator release is associated with
      coronary atherosclerosis and cigarette smoking: direct link between endothelial
      dysfunction and atherothrombosis.
AB  - BACKGROUND: The aim of the study was to establish the influence of proximal
      coronary artery atheroma and smoking habit on the stimulated release of tissue
      plasminogen activator (tPA) from the heart. METHODS AND RESULTS: After diagnostic
      coronary angiography in 25 patients, the left anterior descending coronary artery
      (LAD) was instrumented, and the proximal LAD plaque volume was determined by use
      of intravascular ultrasound (IVUS). Blood flow and fibrinolytic responses to
      selective LAD infusion of saline, substance P (10 to 40 pmol/min; endothelium
      dependent), and sodium nitroprusside (5 to 20 microgram/min; endothelium
      independent) were measured by intracoronary IVUS and Doppler, combined with
      arterial and coronary sinus blood sampling. Mean plaque burden was 5.5+/-0.8
      mm(3)/mm vessel (range 0.6 to 13.7 mm(3)/mm vessel). LAD blood flow increased
      with both substance P and sodium nitroprusside (P<0.001), although coronary sinus
      plasma tPA antigen and activity concentrations increased only during substance P
      infusion (P<0.006 for both). There was a strong inverse correlation between the
      LAD plaque burden and release of active tPA (r=-0.61, P=0.003). Cigarette smoking
      was associated with impaired coronary release of active tPA (current smokers,
      31+/-23 IU/min; ex-smokers, 50+/-33 IU/min; nonsmokers 202+/-73 IU/min; P<0.05).
      CONCLUSIONS: We found that both the coronary atheromatous plaque burden and
      smoking habit are associated with a reduced acute local fibrinolytic capacity of
      the heart. These important findings provide evidence of a direct link between
      endogenous fibrinolysis, endothelial dysfunction, and atherothrombosis in the
      coronary circulation and may explain the greater efficacy of thrombolytic therapy
      for myocardial infarction in cigarette smokers.

PMID- 11306521
TI  - Fluvastatin lowers atherogenic dense low-density lipoproteins in postmenopausal
      women with the atherogenic lipoprotein phenotype.
AB  - BACKGROUND: Although HMG-CoA reductase inhibitors (HMGRIs) are effective lipid
      lowering agents, it remains controversial whether these agents also lower dense
      LDL (dLDL), a predominance of which is considered to contribute to the
      atherogenicity of the metabolic syndrome. METHODS AND RESULTS: In a multicenter,
      double-blind, randomized, placebo-controlled study, we determined the effect of
      the HMGRI fluvastatin on lipids, apolipoproteins, and LDL subfractions (by
      equilibrium density gradient ultracentrifugation). A total of 52 postmenopausal
      women with combined hyperlipidemia and increased dLDL were treated with either
      fluvastatin 40 mg/d (n=35) or placebo (n=17). After 12 weeks' treatment,
      significant reductions (P<0.001) in total cholesterol (-19%), IDL cholesterol (
      35%), LDL cholesterol (-23%), apolipoprotein B (-21%), and apolipoprotein B in
      dLDL (-42%) were apparent among fluvastatin recipients. No significant changes in
      triglycerides or HDL cholesterol were observed. The effect of fluvastatin on dLDL
      was correlated with baseline values. There was no consistent relationship,
      however, between the effect of fluvastatin on triglycerides and the decrease in
      dLDL. CONCLUSIONS: Fluvastatin lowers total and LDL cholesterol and the
      concentration of dLDL. This profile may contribute to an antiatherogenic effect
      for fluvastatin that is greater than expected on the basis of changes in lipids
      and apolipoproteins.

PMID- 11306522
TI  - Cardiovascular status of carriers of the apolipoprotein A-I(Milano) mutant: the
      Limone sul Garda study.
AB  - BACKGROUND: Carriers of the apolipoprotein A-I(Milano) (apoA-I(M)) mutant present
      with very low plasma HDL cholesterol and moderate hypertriglyceridemia,
      apparently not leading to premature coronary heart disease. The objective of this
      study was to establish whether this high-risk lipid/lipoprotein profile is
      associated with structural changes in the carotid arteries and heart, indicative
      of preclinical atherosclerosis. METHODS AND RESULTS: Twenty-one A-I(M) carriers
      were compared with age- and sex-matched control subjects from the same kindred
      and with 2 series of matched subjects with primary hypoalphalipoproteinemia (HA).
      Structural changes in the carotid arteries were defined as the intima-media
      thickness (IMT) measured by B-mode ultrasound. HA subjects, both recruited among
      patients attending our Lipid Clinic and blood donors, showed significant
      thickening of the carotids (average IMT, 0.86+/-0.25 and 0.88+/-0.29 mm,
      respectively) compared with control subjects (average IMT, 0.64+/-0.12 mm); the
      apoA-I(M) carriers instead showed normal arterial thickness (average IMT, 0.63+/
      0.10 mm). Moreover, a significantly higher prevalence of atherosclerotic plaques
      was found in patients and blood donors with HA (both 57%) compared with apoA-I(M)
      carriers (33%) and control subjects (21%). Echocardiographic findings and maximal
      treadmill ECG did not differ significantly between apoA-I(M) carriers and control
      subjects, apart from a slight increase in left ventricular end-diastolic
      dimension in the carriers. CONCLUSIONS: Despite severe HA, carriers of the apoA
      I(M) mutant do not show structural changes in the arteries and heart, in contrast
      to HA subjects, who are characterized by a marked increase in carotid IMT and
      increased prevalence of atherosclerotic plaques.

PMID- 11306523
TI  - Elevated levels of oxidized low density lipoprotein show a positive relationship
      with the severity of acute coronary syndromes.
AB  - BACKGROUND: There is accumulating data that acute coronary syndromes relate to
      recent onset activation of inflammation affecting atherosclerotic plaques.
      Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a
      role in these circumstances. METHODS AND RESULTS: Ox-LDL levels were measured in
      135 patients with acute myocardial infarction (AMI; n=45), unstable angina
      pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control
      subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens
      obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were
      studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were
      significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in
      controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/
      0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein;
      control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and
      LDL cholesterol did not differ among these patient groups. In the atherectomy
      specimens, the surface area containing ox-LDL-positive macrophages was
      significantly higher in patients with UAP than in those with SAP (P<0.0001).
      CONCLUSIONS: This study demonstrates that ox-LDL levels show a significant
      positive correlation with the severity of acute coronary syndromes and that the
      more severe lesions also contain a significantly higher percentage of ox-LDL
      positive macrophages. These observations suggest that increased levels of ox-LDL
      relate to plaque instability in human coronary atherosclerotic lesions.

PMID- 11306524
TI  - Vascular effects of synthetic or natural progestagen combined with conjugated
      equine estrogen in healthy postmenopausal women.
AB  - BACKGROUND: Synthetic, not natural, progestagen may negate the favorable effects
      of estrogen. Nonetheless, observational studies report no differences in risk for
      clinical cardiovascular events between users of unopposed estrogen and users of
      estrogen combined with synthetic progestin. METHODS AND RESULTS: In a double
      blind study, we randomly assigned 20 healthy postmenopausal women to micronized
      progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days
      with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5
      days off cyclically during 2 months, followed by crossover to the alternate
      therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated
      dilator response to hyperemia relative to baseline measurements (P=0.004 by
      ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E
      selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion
      molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by
      ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM
      1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did
      (P=0.040). Both therapies significantly decreased monocyte chemoattractant
      protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree
      (P=0.194). Both therapies significantly decreased tissue factor antigen and
      increased tissue factor activity levels from baseline values (P=0.003 and P<0.001
      by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for
      activity). Both therapies significantly lowered plasma plasminogen activator
      inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree
      (P=0.533). CONCLUSIONS: CEE+MP and CEE+MPA provide similar improvement in
      endothelium-dependent vasodilator responsiveness and effects on markers of
      inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal
      women.

PMID- 11306525
TI  - Stent thrombosis in the modern era: a pooled analysis of multicenter coronary
      stent clinical trials.
AB  - BACKGROUND: There are limited studies of stent thrombosis in the modern era of
      second-generation stents, high-pressure deployment, and current antithrombotic
      regimens. METHODS AND RESULTS: Six recently completed coronary stent trials and
      associated nonrandomized registries that enrolled 6186 patients (6219 treated
      vessels) treated with >/=1 coronary stent followed by antiplatelet therapy with
      aspirin and ticlopidine were pooled for this analysis. Within 30 days, clinical
      stent thrombosis developed in 53 patients (0.9%). The variables most
      significantly associated with the probability of stent thrombosis were persistent
      dissection NHLBI grade B or higher after stenting (OR, 3.7; 95% CI, 1.9 to 7.7),
      total stent length (OR, 1.3; 95% CI, 1.2 to 1.5 per 10 mm), and final minimal
      lumen diameter within the stent (OR, 0.4; 95% CI, 0.2 to 0.7 per 1 mm). Stent
      thrombosis was documented by angiography in 45 patients (0.7%). Clinical
      consequences of angiographic stent thrombosis included 64.4% incidence of death
      or myocardial infarction at the time of stent thrombosis and 8.9% 6-month
      mortality. CONCLUSIONS: Stent thrombosis occurred in <1.0% of patients undergoing
      stenting of native coronary artery lesions and receiving routine antiplatelet
      therapy with aspirin plus ticlopidine. Procedure-related variables of persistent
      dissection, total stent length, and final lumen diameter were significantly
      associated with the probability of stent thrombosis. Continued efforts to
      eliminate this complication are warranted given the serious clinical
      consequences.

PMID- 11306526
TI  - Prognostic value of radionuclide angiography in patients with right ventricular
      arrhythmias.
AB  - BACKGROUND: The prognosis of patients with right ventricular (RV) arrhythmias
      remains uncertain. This study prospectively evaluated the prognostic value of RV
      and left ventricular (LV) involvement assessed by radionuclide angiography (RNA)
      as predictors for sudden death. METHODS AND RESULTS: Patients (n=188) with severe
      arrhythmias originating from the RV were followed up for a mean of 45+/-34
      months. Data on clinical presentation, resting and stress ECG, signal-averaged
      ECG, 24-hour Holter monitoring, and programmed stimulation were collected along
      with RNA. Patients were classified as group I (n=82) with normal RNA or group II
      (n=106) with an abnormal RV suggestive of arrhythmogenic RV cardiomyopathy,
      classified as diffuse or localized disease, with or without associated LV
      abnormalities. During follow-up, 14 patients died suddenly, all in group II. None
      of the clinical and electrical data were predictive of death. An abnormal RNA
      study was a highly predictive factor for death (P<0.005), as well as the presence
      of LV abnormalities (P<0.01). CONCLUSIONS: The present study confirms that
      arrhythmogenic RV cardiomyopathy is a severe disease with a high risk for cardiac
      death. Evidence of RV abnormalities in patients presenting with RV arrhythmias is
      highly predictive for sudden death, as is its association with LV involvement.

PMID- 11306527
TI  - Relationship of heart rate variability to parasympathetic effect.
AB  - BACKGROUND: Baroreflex-mediated parasympathetic stimulation has variable effects
      on heart rate variability (HRV). We postulated that a quadratic function would
      describe the relationship between HRV and parasympathetic effect better than a
      linear function. METHODS AND RESULTS: Twenty-nine normal volunteers (15 women;
      mean age 39+/-12 years) were studied after beta-adrenergic blockade with
      intravenous propranolol. Five-minute ECG recordings were made during graded
      infusions of phenylephrine and nitroprusside to achieve baroreflex-mediated
      increases and decreases in parasympathetic effect, respectively. Time- and
      frequency-domain measures of HRV were calculated from the R-R interval
      tachograms. The R-R interval and the vagal-sympathetic effect (VSE=R-R
      interval/intrinsic R-R interval) were used as indices of parasympathetic effect.
      The data were fit to both quadratic and linear models. In each case, the
      quadratic model (with a negative coefficient for the squared term) was superior
      to the linear model. There was some evidence that age influenced the
      responsiveness of the HRV parameters with changing parasympathetic effect,
      although the regression analysis was significant only in the models for MSSD
      (P<0.03) and pNN50 (P<0.001). CONCLUSIONS: The relationship between HRV and
      parasympathetic effect is best described by a function in which there is an
      ascending limb where HRV increases as parasympathetic effect increases until it
      reaches a plateau level; HRV then decreases as parasympathetic effect increases.
      Because there is marked interindividual variation in this relationship,
      differences in HRV between individuals may reflect differences in this
      relationship and/or differences in autonomic effects.

PMID- 11306528
TI  - Serpin protein CrmA suppresses hypoxia-mediated apoptosis of ventricular
      myocytes.
AB  - BACKGROUND: In this study, we ascertain whether caspase 8 activation and
      mitochondrial defects underlie apoptosis of ventricular myocytes during hypoxia.
      As an approach to circumvent the potential shortcomings surrounding the limited
      permeability and short half-life of the synthetic peptide inhibitors designed to
      block caspase activation, we constructed a replication-defective adenovirus
      encoding the serpin caspase inhibitor protein CrmA to ensure efficient and
      continual inhibition of caspase 8 activity during chronic hypoxia. METHODS AND
      RESULTS: In contrast to normoxic cells, oxygen deprivation of postnatal
      ventricular myocytes for 24 hours resulted in a 9-fold increase (P<0.05) in
      apoptosis as determined by Hoechst 33258 staining and nucleosomal DNA laddering.
      Moreover, hypoxia provoked a 1.5-fold increase (P<0.01) in caspase 8-like
      activity. Furthermore, hypoxia provoked perturbations to mitochondria consistent
      with the mitochondrial death pathway, including permeability transition pore (PT)
      opening, loss of mitochondrial membrane potential ((m)), and cytochrome c
      release. Importantly, CrmA suppressed caspase 8 activity, PT pore changes, loss
      of (m), and apoptosis but had no effect on hypoxia-mediated cytochrome c release.
      Furthermore, Bongkrekic acid, an inhibitor of PT pore, prevented hypoxia-induced
      PT pore changes, loss of (m), and apoptosis but had no effect on hypoxia-mediated
      cytochrome c release. CONCLUSIONS: To our knowledge, we provide the first direct
      evidence for the operation of CrmA as an antiapoptotic factor in ventricular
      myocytes during prolonged durations of hypoxia. Furthermore, our data suggest
      that perturbations to mitochondria including PT pore changes and (m) loss are
      caspase-regulated events that appear to be separable from cytochrome c release.

PMID- 11306529
TI  - Flow-induced dilation of human coronary arterioles: important role of Ca(2+)
      activated K(+) channels.
AB  - BACKGROUND: Flow-induced vasodilation (FID) is a physiological mechanism for
      regulating coronary flow and is mediated largely by nitric oxide (NO) in animals.
      Because hyperpolarizing mechanisms may play a greater role than NO in the
      microcirculation, we hypothesized that hyperpolarization contributes importantly
      to FID of human coronary arterioles. METHODS AND RESULTS: Arterioles from atria
      or ventricles were cannulated for videomicroscopy. Membrane potential of vascular
      smooth muscle cells (VSMCs) was measured simultaneously. After constriction with
      endothelin-1, increases in flow induced an endothelium-dependent vasodilation.
      Nomega-Nitro-L-arginine methyl ester 10(-4) mol/L modestly impaired FID of
      arterioles from patients without coronary artery disease (CAD), whereas no
      inhibition was seen in arterioles from patients with CAD. Indomethacin 10(-5)
      mol/L was without effect, but 40 mmol/L KCl attenuated maximal FID.
      Tetraethylammonium 10(-3) mol/L but not glibenclamide 10(-6) mol/L reduced FID.
      Charybdotoxin 10(-8) mol/L impaired both FID (15+/-3% versus 75+/-12%, P<0.05)
      and hyperpolarization (-32+/-2 mV [from -28+/-2 mV after endothelin-1] versus 
      42+/-2 mV [-27+/-2 mV], P<0.05). Miconazole 10(-6) mol/L or 17-octadecynoic acid
      10(-5) mol/L reduced FID. By multivariate analysis, age was an independent
      predictor for the reduced FID. Conclusions-We conclude that shear stress induces
      endothelium-dependent vasodilation, hyperpolarizing VSMCs through opening Ca(2+)
      activated K(+) channels in human coronary arterioles. In subjects without CAD, NO
      contributes to FID. NO and prostaglandins play no role in patients with CAD;
      rather, cytochrome P450 metabolites are involved. This is consistent with a role
      for endothelium-derived hyperpolarizing factor in FID of the human coronary
      microcirculation.

PMID- 11306530
TI  - Index matching to improve optical coherence tomography imaging through blood.
AB  - BACKGROUND: Most myocardial infarctions are caused by the rupture of small rather
      than large plaques in the arteries of the heart that are beyond the detection
      limit of current technologies. METHODS AND RESULTS: Recently, optical coherence
      tomography (OCT) has demonstrated considerable potential as a method for high
      resolution assessment of vulnerable plaque. However, intravascular OCT imaging is
      complicated by the need to remove blood from the imaging field because blood
      results in substantial signal attenuation. This work examines index matching as a
      method for increasing penetration. Index matching is based on the hypothesis that
      the predominant source of scattering in blood is the difference in refractive
      index between the cytoplasm of erythrocytes and serum. By increasing the
      refractive index of serum to a value near that of the cytoplasm, or index
      matching, scattering can be substantially reduced. The concept was tested with a
      system that pumped blood in vitro through transparent tubing. The test compounds,
      dextran and intravenous contrast agent, both led to significant improvements in
      penetration (69+/-12% and 45+/-4%). No significant effect was seen with the
      saline control. For dextran, the effect could not be attributed to reductions of
      red cell number or volume because changes in these parameters were not different
      from the control. In the case of intravenous contrast, a small but significant
      relative reduction in red cell volume was seen. CONCLUSIONS: This study
      demonstrates the feasibility of index matching for improving OCT imaging through
      blood. Future studies are required to identify compounds for effective index
      matching in vivo.

PMID- 11306531
TI  - Instability and triangulation of the action potential predict serious
      proarrhythmia, but action potential duration prolongation is antiarrhythmic.
AB  - BACKGROUND: Prolongation of action potential duration (APD) is considered a major
      antiarrhythmic mechanism (class 2I), but paradoxically, it frequently is also
      proarrhythmic (torsade de pointes). METHODS AND RESULTS: The cardiac
      electrophysiological effects of 702 chemicals (class 2I or HERG channel block)
      were studied in 1071 rabbit Langendorff-perfused hearts. Temporal instability of
      APD, triangulation (duration of phase 3 repolarization), reverse use-dependence,
      and induction of ectopic beats were measured. Instability, triangulation, and
      reverse use-dependence were found to be important determinants of proarrhythmia.
      Agents that lengthened the APD by >50 ms, with induction of instability,
      triangulation, and reverse use-dependence (n=59), induced proarrhythmia
      (primarily polymorphic ventricular tachycardia); in their absence (n=19), the
      same prolongation of APD induced no proarrhythmia but significant antiarrhythmia
      (P<0.001). Shortening of APD, when accompanied by instability and triangulation,
      was also markedly proarrhythmic (primarily monomorphic ventricular tachycardia).
      In experiments in which instability and triangulation were present, proarrhythmia
      declined with prolongation of APD, but this effect was not large enough to become
      antiarrhythmic. Only with agents without instability did prolongation of APD
      become antiarrhythmic. For 20 selected compounds, it was shown that instability
      of APD and triangulation observed in vitro were strong predictors of in vivo
      proarrhythmia (torsade de pointes). CONCLUSIONS: Lengthening of APD without
      instability or triangulation is not proarrhythmic but rather antiarrhythmic.

PMID- 11306532
TI  - Deficiency of urokinase-type plasminogen activator-mediated plasmin generation
      impairs vascular remodeling during hypoxia-induced pulmonary hypertension in
      mice.
AB  - BACKGROUND: Chronic hypoxia results in the development of pulmonary hypertension
      and subsequent right heart failure. A role of the plasminogen system in the
      pathogenesis of pulmonary hypertension and pulmonary vascular remodeling has been
      suggested. METHODS AND RESULTS: Mice with targeted deficiency of the gene
      encoding tissue-type plasminogen activator (t-PA(-/-)), urokinase-type
      plasminogen activator (u-PA(-/-)), u-PA receptor (u-PAR(-/-)), or plasminogen
      (plg(-/-)) were subjected to hypoxic conditions. Hypoxia caused a significant 2.5
      fold rise in right ventricular pressure in wild-type mice. Deficiency of u-PA or
      plasminogen prevented this increase in right ventricular pressure, t-PA(-/-) mice
      showed changes that were fully comparable with wild-type mice, and u-PAR(-/-)
      mice showed a partial response. Hypoxia induced an increase in smooth muscle
      cells within pulmonary arterial walls and a vascular rarefaction in the lungs of
      wild-type but not of u-PA(-/-) or plg(-/-) mice. Elastic lamina fragmentation,
      observed in hypoxic wild-type but not in u-PA or plasminogen-deficient mice,
      suggested that proliferation of vascular smooth muscle cells was dependent on u
      PA-mediated elastic membrane degradation. Hypoxia-induced right ventricular
      remodeling in wild-type mice, characterized by cardiomyocyte hypertrophy and
      increased collagen contents, was not seen in u-PA(-/-) and plg(-/-) mice.
      CONCLUSIONS: Loss of the u-PA or plasminogen gene protects against the
      development of hypoxia-induced pulmonary hypertension and pulmonary vascular
      remodeling. These observations point to an essential role of u-PA-mediated
      plasmin generation in the adaptive response to chronic hypoxia and the occurrence
      of hypoxic pulmonary vascular disease.

PMID- 11306533
TI  - Assessment of myocardial postreperfusion viability by intravenous myocardial
      contrast echocardiography: analysis of the intensity and texture of
      opacification.
AB  - BACKGROUND: Although defects on intracoronary myocardial contrast
      echocardiography (MCE) indicate loss of viability after reperfusion, opacified
      segments may also exhibit persistent dyssynergy. Therefore, we related the
      intensity and texture of opacification produced by an intravenous contrast agent
      to histological findings to determine the characteristics of necrotic tissue by
      postreperfusion MCE. METHODS AND RESULTS: MCE was performed by intravenous
      injection of 0.15 mL/kg QW7437 in 14 dogs who underwent 3-hour coronary occlusion
      followed by 3-hour reperfusion. At baseline and 3 hours after reperfusion,
      midventricular short-axis images were digitized and segmented. Infarction
      fraction (IF) for each segment was determined by triphenyltetrazolium chloride
      stain. Of 224 segments, 140 showed no or small infarction and served as a control
      group. Of 84 segments with significant infarction (IF>30%), 52 exhibited a defect
      on MCE, and 32 exhibited no defect. Echo texture was quantified by computing
      entropy based on the co-occurrence matrix analysis of gray-level pairs within
      each segment. Three hours after reperfusion, average and maximal entropies in the
      infarct segments without opacification defects were significantly higher than
      control levels. Histologically, the degree of intracapillary erythrocyte stasis
      was less in this group than in the infarcted segments with MCE defects with
      similar magnitude of tissue injuries. CONCLUSIONS: Opacification defects by MCE
      may be present or absent in myocardium with histologically confirmed infarction.
      The texture of MCE from opacified but infarcted myocardium differed significantly
      from control segments and may assist in determination of segmental viability
      after reperfusion.

PMID- 11306534
TI  - Left main coronary artery to left atrial fistula causing mild pulmonary
      hypertension.

PMID- 11306535
TI  - Cine magnetic resonance imaging of myocardial ischemia and reperfusion in mice.

PMID- 11306537
TI  - Blame the press?

PMID- 11306538
TI  - Genetically modified crops: hope for developing countries? The current GM debate
      widely ignores the specific problems of farmers and consumers in the developing
      world.

PMID- 11306539
TI  - A vision for European science: more integration and a long-term policy is needed.

PMID- 11306540
TI  - Cashing in on nature's pharmacy: Bioprospecting and protection of biodiversity
      could go hand in hand.

PMID- 11306541
TI  - The same, only different. Postdoctoral experience in Japan: an alternative worth
      considering.

PMID- 11306542
TI  - Science--love it or hate it? A young scientist's view of the public relations
      problem of European science and the possible solutions.

PMID- 11306546
TI  - Cell migration: GAPs between membrane traffic and the cytoskeleton.
AB  - During cell migration, coordination between membrane traffic, cell substrate
      adhesion and actin reorganization is required for protrusive activity to occur at
      the leading edge. Actin organization is regulated by Rho family GTPases and, with
      a contribution from the endocytic cycle, serves to extend the cell front. The
      details of the molecular mechanisms that direct membrane traffic at sites of
      adhesion and rearrange actin at the cell edge are still unknown. However, recent
      findings show that a number of multi-domain proteins characterized by an ArfGAP
      domain interact with both actin-regulating and integrin-binding proteins, as well
      as affecting Rac-mediated protrusive activity and cell migration. Some of these
      proteins have been shown to localize to endocytic compartments and to have a role
      in regulating endocytosis. Given the participation of Arf proteins in regulating
      membrane traffic, one appealing hypothesis is that the ArfGAPs act as molecular
      devices that coordinate membrane traffic and cytoskeletal reorganization during
      cell motility.

PMID- 11306547
TI  - Mechanisms of nutritional and hormonal regulation of lipogenesis.
AB  - Fat build-up is determined by the balance between lipogenesis and lipolysis/fatty
      acid oxidation. In the past few years, our understanding of the nutritional,
      hormonal and particularly transcriptional regulation of lipogenesis has expanded
      greatly. Lipogenesis is stimulated by a high carbohydrate diet, whereas it is
      inhibited by polyunsaturated fatty acids and by fasting. These effects are partly
      mediated by hormones, which inhibit (growth hormone, leptin) or stimulate
      (insulin) lipogenesis. Recent research has established that sterol regulatory
      element binding protein-1 is a critical intermediate in the pro- or anti
      lipogenic action of several hormones and nutrients. Another transcription factor
      implicated in lipogenesis is the peroxisome proliferator activated receptor
      gamma. Both transcription factors are attractive targets for pharmaceutical
      intervention of disorders such as hypertriglyceridemia and obesity.

PMID- 11306548
TI  - Homologous recombination in planta is stimulated in the absence of Rad50.
AB  - Chromosomal double-strand DNA breaks must be repaired; in the absence of repair
      the resulting acentromeric (and telomereless) fragments may be lost and/or the
      broken DNA ends may recombine causing general chromosomal instability. The
      Rad50/Mre11/Xrs2 protein complex acts at DNA ends and is implicated in both
      homologous and non-homologous recombination. We have isolated a rad50 mutant of
      the plant Arabidopsis thaliana and show here that it has a somatic hyper
      recombination phenotype in planta. This finding supports the hypothesis of a
      competition between homologous and illegitimate recombination in higher
      eukaryotes. To our knowledge, this is the first direct in vivo support for the
      role of this complex in chromosomal recombination in a multicellular organism and
      the first description of a mutation of a known gene leading to hyper
      recombination in plants.

PMID- 11306549
TI  - A highly efficient ligand-regulated Cre recombinase mouse line shows that LoxP
      recombination is position dependent.
AB  - Conditional gene inactivation using the Cre/loxP system is widely used, but the
      difficulty in properly regulating Cre expression remains one of the bottlenecks.
      One approach to regulate Cre activity utilizes a mutant estrogen hormone-binding
      domain (ERT) to keep Cre inactive unless the non-steroidal estrogen analog 4
      hydroxytamoxifen (OHT) is present. Here we describe a mouse strain expressing Cre
      ERT from the ubiquitously expressed ROSA26 (R26) locus. We demonstrate efficient
      temporal and spatial regulation of Cre recombination in vivo and in primary cells
      derived from these mice. We show the existence of marked differences in
      recombination frequencies between different substrates within the same cell. This
      has important consequences when concurrent switching of multiple alleles within
      the same cell is needed, and highlights one of the difficulties that may be
      encountered when using reporter mice as indicator strains.

PMID- 11306550
TI  - Direct competition between Brinker and Drosophila Mad in Dpp target gene
      transcription.
AB  - Brinker is a nuclear protein that antagonizes Dpp signalling in Drosophila. Its
      expression is negatively regulated by Dpp. Here, we show that Brinker represses
      Ultrabithorax (Ubx) in the embryonic midgut, a HOX gene that activates, and
      responds to, the localized expression of Dpp during endoderm induction. We find
      that the functional target for Brinker repression coincides with the Dpp response
      sequence in the Ubx midgut enhancer, namely a tandem of binding sites for the Dpp
      effector Mad. We show that Brinker efficiently competes with Mad in vitro,
      preventing the latter from binding to these sites. Brinker also competes with
      activated Mad in vivo, blocking the stimulation of the Ubx enhancer in response
      to simultaneous Dpp signalling. These results indicate how Brinker acts as a
      dominant repressor of Dpp target genes, and explain why Brinker is a potent
      antagonist of Dpp.

PMID- 11306551
TI  - Perturbation of the tight junction permeability barrier by occludin loop peptides
      activates beta-catenin/TCF/LEF-mediated transcription.
AB  - Here we show that interference with the integrity of the transepithelial
      permeability barrier of mouse mammary epithelial cells by treatment with
      synthetic peptides, homologous to the second extracellular domain of occludin,
      decreased the amount of occludin protein present at tight junctions and led to
      the formation of multilayered, unpolarized cell clusters. In addition,
      transcription of the adherens junction protein beta-catenin was induced.
      Following accumulation of soluble beta-catenin protein, transcription by beta
      catenin/TCF/LEF was increased, as revealed by transcriptional assays following
      transient transfection of the reporter construct. Furthermore, treatment with
      occludin-II peptides up-regulated RNA levels of the known beta-catenin/TCF/LEF
      downstream target gene c-myc. The data presented imply a functional cross-talk
      between tight and adherens junctions that possibly contributes to the stepwise
      transformation during oncogenesis.

PMID- 11306552
TI  - Three-dimensional reconstruction of a recombinant influenza virus
      ribonucleoprotein particle.
AB  - A three-dimensional structural model of an influenza virus ribonucleoprotein
      particle reconstituted in vivo from recombinant proteins and a model genomic vRNA
      has been generated by electron microscopy. It shows a circular shape and contains
      nine nucleoprotein monomers, two of which are connected with the polymerase
      complex. The nucleoprotein monomers show a curvature that may be responsible for
      the formation of helical structures in the full-size viral ribonucleoproteins.
      The monomers show distinct contact boundaries at the two sides of the particle,
      suggesting that the genomic RNA may be located in association with the
      nucleoprotein at the base of the ribonucleoprotein complex. Sections of the three
      dimensional model show a trilobular morphology in the polymerase complex that is
      consistent with the presence of its three subunits.

PMID- 11306553
TI  - Structural basis for selectivity and toxicity of ribosomal antibiotics.
AB  - Ribosomal antibiotics must discriminate between bacterial and eukaryotic
      ribosomes to various extents. Despite major differences in bacterial and
      eukaryotic ribosome structure, a single nucleotide or amino acid determines the
      selectivity of drugs affecting protein synthesis. Analysis of resistance
      mutations in bacteria allows the prediction of whether cytoplasmic or
      mitochondrial ribosomes in eukaryotic cells will be sensitive to the drug. This
      has important implications for drug specificity and toxicity. Together with
      recent data on the structure of ribosomal subunits these data provide the basis
      for development of new ribosomal antibiotics by rationale drug design.

PMID- 11306554
TI  - Stoichiometry and kinetics of transport vesicle fusion with Golgi membranes.
AB  - The in vitro complementation assay established by Rothman and co-workers
      continues to be an important tool to study intra-Golgi transport. In this study,
      kinetic modeling is used to identify four main parameters that, together, explain
      the basic features of an assay that is a modification of the original assay.
      First, the assay signal depends on the ratio of Golgi membranes to transport
      intermediates in the assay. Secondly, an inactivation rate describes how the
      activity of transport intermediates decreases over time. Thirdly, the rate at
      which transport intermediates irreversibly bind to Golgi membranes is measured
      independently of membrane fusion, thus allowing a quantitative distinction
      between these two steps. Fourthly, a single rate constant describes the remaining
      reactions, which result in membrane fusion. This approach of kinetic modeling of
      experiments is generally applicable to other in vitro assays of cell biological
      phenomena, permitting quantitative interpretations and an increased resolution of
      the experiments.

PMID- 11306555
TI  - Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi
      network.
AB  - Autophagy is an intracellular bulk protein degradation system. Beclin is known to
      be involved in this process; however, its role is unclear. In this study, we
      showed that Beclin was co-immunoprecipitated with phosphatidylinositol (PtdIns) 3
      kinase, which is also required for autophagy, suggesting that Beclin is a
      component of the PtdIns 3-kinase complex. Quantitative analyses using a cross
      linker showed that all Beclin forms a complex with PtdIns 3-kinase, whereas
      approximately 50% of PtdIns 3-kinase remains free from Beclin. Indirect
      immunofluorescence microscopy demonstrated that the majority of Beclin and PtdIns
      3-kinase localize to the trans-Golgi network (TGN). Some PtdIns 3-kinase is also
      distributed in the late endosome. These results suggest that Beclin and PtdIns 3
      kinase control autophagy as a complex at the TGN.

PMID- 11306556
TI  - The Golgi matrix protein GM130: a specific interacting partner of the small
      GTPase rab1b.
AB  - To detect specific partners of the small Golgi-localized GTPase rab1b we
      generated rab1b mutants and used them as bait proteins in yeast two-hybrid
      screens. We isolated several specifically interacting clones. Two of them encode
      large protein fragments highly homologous to rat GM130 and to human Golgin95. The
      full-length human GM130 cDNA was cloned and its interaction with rab1b was
      characterized in detail by yeast two-hybrid and in vitro binding assays. Here we
      report for the first time that the rab1b protein interacts specifically with
      GM130 in a GTP-dependent manner and therefore needs the hypervariable regions of
      the N- and C-termini. We mapped the rab1b binding site of GM130 and provide
      evidence that it is different to the previously described p115 and Grasp65
      binding sites of the GM130 protein.

PMID- 11306557
TI  - Association of structural polymorphisms in the human period3 gene with delayed
      sleep phase syndrome.
AB  - Recent progress in biological clock research has facilitated genetic analysis of
      circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and
      non-24-h sleep-wake syndrome (N-24). We analyzed the human period3 (hPer3) gene,
      one of the human homologs of the Drosophila clock-gene period (Per), as a
      possible candidate for rhythm disorder susceptibility. All of the coding exons in
      the hPer3 gene were screened for polymorphisms by a PCR-based strategy using
      genomic DNA samples from sleep disorder patients and control subjects. We
      identified six sequence variations with amino acid changes, of which five were
      common and predicted four haplotypes of the hPer3 gene. One of the haplotypes was
      significantly associated with DSPS (Bonferroni's corrected P = 0.037; odds ratio
      = 7.79; 95% CI 1.59-38.3) in our study population. Our results suggest that
      structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis
      of DSPS.

PMID- 11306558
TI  - Normal neurogenesis and scrapie pathogenesis in neural grafts lacking the prion
      protein homologue Doppel.
AB  - The agent that causes prion diseases is thought to be identical to PrPSc, a
      conformer of the normal prion protein PrPC. Recently a novel protein, termed
      Doppel (Dpl), was identified that shares significant biochemical and structural
      homology with PrPC. To investigate the function of Dpl in neurogenesis and in
      prion pathology, we generated embryonic stem (ES) cells harbouring a homozygous
      disruption of the Prnd gene that encodes Dpl. After in vitro differentiation and
      grafting into adult brains of PrPC-deficient Prnp0/0 mice, Dpl-deficient ES cell
      derived grafts contained all neural lineages analyzed, including neurons and
      astrocytes. When Prnd-deficient neural tissue was inoculated with scrapie prions,
      typical features of prion pathology including spongiosis, gliosis and PrPSc
      accumulation, were observed. Therefore, Dpl is unlikely to exert a cell
      autonomous function during neural differentiation and, in contrast to its
      homologue PrPC, is dispensable for prion disease progression and for generation
      of PrPSc.

PMID- 11306559
TI  - Folding of prion protein to its native alpha-helical conformation is under
      kinetic control.
AB  - The recombinant mouse prion protein (MoPrP) can be folded either to a monomeric
      alpha-helical or oligomeric beta-sheet-rich isoform. By using circular dichroism
      spectroscopy and size-exclusion chromatography, we show that the beta-rich
      isoform of MoPrP is thermodynamically more stable than the native alpha-helical
      isoform. The conformational transition from the alpha-helical to beta-rich
      isoform is separated by a large energetic barrier that is associated with
      unfolding and with a higher order kinetic process related to oligomerization.
      Under partially denaturing acidic conditions, MoPrP avoids the kinetic trap posed
      by the alpha-helical isoform and folds directly to the thermodynamically more
      stable beta-rich isoform. Our data demonstrate that the folding of the prion
      protein to its native alpha-helical monomeric conformation is under kinetic
      control.

PMID- 11306561
TI  - Discovery of a novel enzyme, isonitrile hydratase, involved in nitrogen-carbon
      triple bond cleavage.
AB  - Isonitrile containing an N triple bond C triple bond was degraded by
      microorganism sp. N19-2, which was isolated from soil through a 2-month
      acclimatization culture in the presence of this compound. The isonitrile
      degrading microorganism was identified as Pseudomonas putida. The microbial
      degradation was found to proceed through an enzymatic reaction, the isonitrile
      being hydrated to the corresponding N-substituted formamide. The enzyme, named
      isonitrile hydratase, was purified and characterized. The native enzyme had a
      molecular mass of about 59 kDa and consisted of two identical subunits. The
      enzyme stoichiometrically catalyzed the hydration of cyclohexyl isocyanide (an
      isonitrile) to N-cyclohexylformamide, but no formation of other compounds was
      detected. The apparent K(m) value for cyclohexyl isocyanide was 16.2 mm. Although
      the enzyme acted on various isonitriles, no nitriles or amides were accepted as
      substrates.

PMID- 11306560
TI  - Pathogenic Neisseria trigger expression of their carcinoembryonic antigen-related
      cellular adhesion molecule 1 (CEACAM1; previously CD66a) receptor on primary
      endothelial cells by activating the immediate early response transcription
      factor, nuclear factor-kappaB.
AB  - Neisseria gonorrhoeae express opacity-associated (Opa) protein adhesins that
      mediate binding to various members of the carcinoembryonic antigen-related
      cellular adhesion molecule (CEACAM; previously CD66) receptor family. Although
      human umbilical vein endothelial cells express little CEACAM receptor in vitro,
      we found neisserial infection to induce expression of CEACAM1, CEACAM1-3L, and
      CECAM1-4L splice variants. This mediates an increased Opa(52)-dependent binding
      of gonococci by these cells. The induced receptor expression did not require
      bacterial Opa expression, but it was more rapid with adherent bacteria. Because
      the time course of induction was similar to that seen for induced proinflammatory
      cytokines, we tested whether CEACAM1 expression could be controlled by a similar
      mechanism. Gonococcal infection activated a nuclear factor-kappaB (NF-kappaB)
      heterodimer consisting of p50 and p65, and inhibitors that prevent the nuclear
      translocation of activated NF-kappaB complex inhibited CEACAM1 transcript
      expression. Each of these effects could be mimicked by using culture filtrates or
      purified lipopolysaccharide instead of intact bacteria. Together, our results
      support a model whereby the outer membrane "blebs" that are actively released by
      gonococci trigger a Toll-like receptor-4-dependent activation of NF-kappaB, which
      up-regulates the expression of CEACAM1 to allow Opa(52)-mediated neisserial
      binding. The regulation of CEACAM1 expression by NF-kappaB also implies a broader
      role for this receptor in the general inflammatory response to infection.

PMID- 11306562
TI  - Nucleo-cytoplasmic trafficking of metal-regulatory transcription factor 1 is
      regulated by diverse stress signals.
AB  - The metal-regulatory transcription factor 1 (MTF-1) is a key regulator of heavy
      metal-induced transcription of metallothionein I and II and other genes in
      mammals and other metazoans. Transcriptional activation of genes by MTF-1 is
      mediated through binding to metal-responsive elements of consensus TGCRCNC in the
      target gene promoters. In an attempt to further clarify the mechanisms by which
      certain external signals activate MTF-1 and in turn modulate gene transcription,
      we show here that human MTF-1 has a dual nuclear and cytoplasmic localization in
      response to diverse stress stimuli. MTF-1 contains a consensus nuclear
      localization signal located just N-terminal to the first zinc finger that
      contributes to but is not essential for nuclear import. MTF-1 also harbors a
      leucine-rich, nuclear export signal. Under resting conditions, the nuclear export
      signal is required for cytoplasmic localization of MTF-1 as indicated by
      mutational analysis and transfer to the heterologous green fluorescent protein.
      Export from the nucleus was inhibited by leptomycin B, suggesting the involvement
      of the nuclear export protein CRM1. Our results further show that in addition to
      the heavy metals zinc and cadmium, heat shock, hydrogen peroxide, low
      extracellular pH (pH 6.0), inhibition of protein synthesis by cycloheximide, and
      serum induce nuclear accumulation of MTF-1. However, heavy metals alone (and not
      the other stress conditions) induce a significant transcriptional response via
      metal-responsive element promoter sequences, implying that nuclear import of MTF
      1 is necessary but not sufficient for transcriptional activation. Possible roles
      for nuclear import under non-metal stress conditions are discussed.

PMID- 11306563
TI  - Cloning and characterization of MST4, a novel Ste20-like kinase.
AB  - MST4, a novel member of the germinal center kinase subfamily of human Ste20-like
      kinases, was cloned and characterized. Composed of a C-terminal regulatory domain
      and an N-terminal kinase domain, MST4 is most closely related to mammalian Ste20
      kinase family member MST3. Both the kinase and C-terminal regulatory domains of
      MST4 are required for full activation of the kinase. Northern blot analysis
      indicates that MST4 is ubiquitously distributed, and the MST4 gene is localized
      to chromosome Xq26, a disease-rich region, by fluorescence in situ hybridization.
      Although some members of the MST4 family function as upstream regulators of
      mitogen-activated protein kinase cascades, expression of MST4 in 293 cells was
      not sufficient to activate or potentiate extracellular signal-regulated kinase, c
      Jun N-terminal kinase, or p38 kinase. An alternatively spliced isoform of MST4
      (MST4a) was isolated by yeast two-hybrid interaction with the catalytic domain of
      Raf from a human fetal brain cDNA library and also found in a variety of human
      fetal and adult tissues. MST4a lacks an exon encoding kinase subdomains IX-XI
      that stabilizes substrate binding. The existence of both MST4 isoforms suggests
      that the MST4 kinase activity is highly regulated, and MST4a may function as a
      dominant-negative regulator of the MST4 kinase.

PMID- 11306565
TI  - Interactions within the coiled-coil domain of RetGC-1 guanylyl cyclase are
      optimized for regulation rather than for high affinity.
AB  - RetGC-1, a member of the membrane guanylyl cyclase family of proteins, is
      regulated in photoreceptor cells by a Ca(2+)-binding protein known as GCAP-1.
      Proper regulation of RetGC-1 is essential in photoreceptor cells for normal light
      adaptation and recovery to the dark state. In this study we show that cGMP
      synthesis by RetGC-1 requires dimerization, because critical functions in the
      catalytic site must be provided by each of the two polypeptide chains of the
      dimer. We also show that an intact alpha-helical coiled-coil structure is
      required to provide dimerization strength for the catalytic domain of RetGC-1.
      However, the dimerization strength of this domain must be precisely optimized for
      proper regulation by GCAP-1. We found that Arg(838) within the dimerization
      domain establishes the Ca(2+) sensitivity of RetGC-1 by determining the strength
      of the coiled-coil interaction. Arg(838) substitutions dominantly enhance cGMP
      synthesis even at the highest Ca(2+) concentrations that occur in normal dark
      adapted photoreceptor cells. Molecular dynamics simulations suggest that Arg(838)
      substitutions disrupt a small network of salt bridges to allow an abnormal
      extension of coiled-coil structure. Substitutions at Arg(838) were first
      identified by linkage to the retinal degenerative disease, autosomal dominant
      cone rod dystrophy (adCORD). Consistent with the characteristics of this disease,
      the Arg(838)-substituted RetGC-1 mutants exhibit a dominant biochemical
      phenotype. We propose that accelerated cGMP synthesis in humans with adCORD is
      the primary cause of cone-rod degeneration.

PMID- 11306564
TI  - Effects of the beta-amyloid and carboxyl-terminal fragment of Alzheimer's amyloid
      precursor protein on the production of the tumor necrosis factor-alpha and matrix
      metalloproteinase-9 by human monocytic THP-1.
AB  - To explore the direct role of beta-amyloid (Abeta) and carboxyl-terminal
      fragments of amyloid precursor protein in the inflammatory processes possibly
      linked to neurodegeneration associated with Alzheimer's disease, the effects of
      the 105-amino acid carboxyl-terminal fragment (CT(105)) of amyloid precursor
      protein on the production of tumor necrosis factor-alpha (TNF-alpha) and matrix
      metalloproteinase-9 (MMP-9) were examined in a human monocytic THP-1 cell line
      and compared with that of Abeta. CT(105) elicited a marked increase in TNF-alpha
      and MMP-9 production in the presence of interferon-gamma in a dose- and time
      dependent manner. Similar patterns were obtained with Abeta despite its low
      magnitude of induction. Autocrine TNF-alpha is likely to be a main mediator of
      the induction of MMP-9 because the neutralizing antibody to TNF-alpha inhibits
      MMP-9 production. Genistein, a specific inhibitor of tyrosine kinase,
      dramatically diminished both TNF-alpha secretion and subsequent MMP-9 release in
      response to CT(105) or Abeta. Furthermore, PD98059 and SB202190, specific
      inhibitors of ERK or p38 MAPK respectively, efficiently suppressed CT(105)
      induced effects whereas only PD98059 was effective at reducing Abeta-induced
      effects. Our results suggest that CT(105) in combination with interferon-gamma
      might serve as a more potent activator than Abeta in triggering inflammatory
      processes and that both tyrosine kinase and MAPK signaling pathways may represent
      potential therapeutic targets for the control of Alzheimer's disease progression.

PMID- 11306566
TI  - The cytokines tumor necrosis factor-alpha (TNF-alpha ) and TNF-related apoptosis
      inducing ligand differentially modulate proliferation and apoptotic pathways in
      human keratinocytes expressing the human papillomavirus-16 E7 oncoprotein.
AB  - Keratinocytes are the natural target cells for infection by human
      papillomaviruses (HPVs), most of which cause benign epithelial hyperplasias
      (warts). However, a subset of papillomaviruses, the "high risk" HPVs, cause
      lesions that can progress to carcinomas. Inflammatory mediators such as tumor
      necrosis factor-alpha (TNF-alpha) and TNF-related apoptosis-inducing ligand
      (TRAIL) are produced by cells in response to a viral infection. To determine the
      effects of TNF-alpha and TRAIL on keratinocytes expressing the high risk HPV-16
      oncoprotein E7, human foreskin keratinocytes stably expressing E7 were treated
      with TNF-alpha and TRAIL. Treatment with TNF-alpha alone, but not TRAIL, induced
      growth arrest and differentiation in keratinocytes that was almost completely
      overcome by expression of HPV-16 E7. Both cytokines induced apoptosis when
      administered in combination with the protein synthesis inhibitor cycloheximide,
      but the apoptotic response to TRAIL was significantly more rapid and efficient
      compared with the response seen after TNF-alpha treatment. HPV-16 E7-expressing
      keratinocytes were more prone to both TNF-alpha- and TRAIL-mediated apoptosis
      compared with vector-infected controls.

PMID- 11306567
TI  - Calexcitin B is a new member of the sarcoplasmic calcium-binding protein family.
AB  - Calexcitin (CE) is a calcium sensor protein that has been implicated in
      associative learning. The CE gene was previously cloned from the long-finned
      squid, Loligo pealei, and the gene product was shown to bind GTP and modulate
      K(+) channels and ryanodine receptors in a Ca(2+)-dependent manner. We cloned a
      new gene from L. pealei, which encodes a CE-like protein, here named calexcitin B
      (CE(B)). CE(B) has 95% amino acid identity to the original form. Our sequence
      analyses indicate that CEs are homologous to the sarcoplasmic calcium-binding
      protein subfamily of the EF-hand superfamily. Far and near UV circular dichroism
      and nuclear magnetic resonance studies demonstrate that CE(B) binds Ca(2+) and
      undergoes a conformational change. CE(B) is phosphorylated by protein kinase C,
      but not by casein kinase II. CE(B) does not bind GTP. Western blot experiments
      using polyclonal antibodies generated against CE(B) showed that CE(B) is
      expressed in the L. pealei optic lobe. Taken together, the neuronal protein CE
      represents the first example of a Ca(2+) sensor in the sarcoplasmic calcium
      binding protein family.

PMID- 11306569
TI  - Amylosucrase, a glucan-synthesizing enzyme from the alpha-amylase family.
AB  - Amylosucrase (E.C. 2.4.1.4) is a member of Family 13 of the glycoside hydrolases
      (the alpha-amylases), although its biological function is the synthesis of
      amylose-like polymers from sucrose. The structure of amylosucrase from Neisseria
      polysaccharea is divided into five domains: an all helical N-terminal domain that
      is not similar to any known fold, a (beta/alpha)(8)-barrel A-domain, B- and B'
      domains displaying alpha/beta-structure, and a C-terminal eight-stranded beta
      sheet domain. In contrast to other Family 13 hydrolases that have the active site
      in the bottom of a large cleft, the active site of amylosucrase is at the bottom
      of a pocket at the molecular surface. A substrate binding site resembling the
      amylase 2 subsite is not found in amylosucrase. The site is blocked by a salt
      bridge between residues in the second and eight loops of the (beta/alpha)(8)
      barrel. The result is an exo-acting enzyme. Loop 7 in the amylosucrase barrel is
      prolonged compared with the loop structure found in other hydrolases, and this
      insertion (forming domain B') is suggested to be important for the polymer
      synthase activity of the enzyme. The topology of the B'-domain creates an active
      site entrance with several ravines in the molecular surface that could be used
      specifically by the substrates/products (sucrose, glucan polymer, and fructose)
      that have to get in and out of the active site pocket.

PMID- 11306568
TI  - An essential role for Mad homology domain 1 in the association of Smad3 with
      histone deacetylase activity*.
AB  - The Smads are a family of sequence-specific DNA-binding proteins that modulate
      transcription in response to transforming growth factor beta (TGFbeta) by
      recruiting transcriptional activators like the histone acetyltransferase,
      p300/CBP, or repressors like the histone deacetylase, HDAC1, to TGFbeta target
      genes. The association of Smads and HDAC1 is mediated in part by direct binding
      of Smads to the HDAC1-associated proteins, TG-interacting factor, c-ski, and
      SnoN. Although ectopic expression of these proteins inhibits Smad-activated
      transcription, the contribution of histone deacetylase enzymatic activity to
      transcriptional repression by TGFbeta is unknown. Here, the biological
      requirements for the interaction between Smads and endogenous histone deacetylase
      activity are investigated. We identify residues in Mad homology domain 1 of Smad3
      that are required for association with histone deacetylase activity. An amino
      acid change at one of these critical residues does not disrupt the association of
      Smad3 with c-ski, SnoN, and transforming growth-interacting factor but does
      abrogate the ability of Smad3 to repress transcription. These findings indicate
      that the association of Smad3 and histone deacetylase activity relies on
      additional protein mediators that make contact with Smad3 at its amino terminus.
      Moreover, these data suggest that the suppressive effect of Smad3 on
      transcription is dependent upon its association with histone deacetylase
      enzymatic activity.

PMID- 11306570
TI  - Molecular basis for the homophilic activated leukocyte cell adhesion molecule
      (ALCAM)-ALCAM interaction.
AB  - Activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the
      immunoglobulin superfamily with five extracellular immunoglobulin-like domains,
      facilitates heterophilic (ALCAM-CD6) and homophilic (ALCAM-ALCAM) cell-cell
      interactions. While expressed in a wide variety of tissues and cells, ALCAM is
      restricted to subsets of cells usually involved in dynamic growth and/or
      migration processes. A structure-function analysis, using two monoclonal anti
      ALCAM antibodies and a series of amino-terminally deleted ALCAM constructs,
      revealed that homophilic cell adhesion depended on ligand binding mediated by the
      membrane-distal amino-terminal immunoglobulin domain and on avidity controlled by
      ALCAM clustering at the cell surface involving membrane-proximal immunoglobulin
      domains. Co-expression of a transmembrane ALCAM deletion mutant, which lacks the
      ligand binding domain, and endogenous wild-type ALCAM inhibited homophilic cell
      cell interactions by interference with ALCAM avidity, while homophilic, soluble
      ligand binding remained unaltered. The extracellular structures of ALCAM thus
      provide two structurally and functionally distinguishable modules, one involved
      in ligand binding and the other in avidity. Functionality of both modules is
      required for stable homophilic ALCAM-ALCAM cell-cell adhesion.

PMID- 11306571
TI  - Uncoupling farnesol-induced apoptosis from its inhibition of phosphatidylcholine
      synthesis.
AB  - Genetic inactivation of the synthesis of phosphatidylcholine, the most abundant
      membrane lipid in eukaryotic cells, induces apoptosis. Administration of
      farnesol, a catabolite within the isoprenoid/cholesterol pathway, also induces
      apoptosis. The mechanism by which farnesol induces apoptosis is currently
      believed to be by direct competitive inhibition with diacylglycerol for
      cholinephosphotransferase, the final step in the phosphatidylcholine biosynthetic
      pathway. Our recent isolation of the first mammalian cholinephosphotransferase
      cDNA has enabled us to more precisely assess how farnesol affects
      phosphatidylcholine synthesis and the induction of apoptosis. Induced over
      expression of cholinephosphotransferase in Chinese hamster ovary cells prevented
      the block in phosphatidylcholine biosynthesis associated with exposure to
      farnesol. However, induced over-expression of cholinephosphotransferase was not
      sufficient for the prevention of farnesol-induced apoptosis. In addition,
      exogenous administration of diacylglycerol prevented farnesol-induced apoptosis
      but did not relieve the farnesol-induced block in phosphatidylcholine synthesis.
      We also developed an in vitro lipid mixed micelle cholinephosphotransferase
      enzyme assay, as opposed to the delivery of the diacylglycerol substrate in a
      detergent emulsion, and demonstrated that there was no direct inhibition of
      cholinephosphotransferase by farnesol or its phosphorylated metabolites. The
      execution of apoptosis by farnesol appears to be a separate and distinct event
      from farnesol-induced inhibition of phosphatidylcholine biosynthesis and instead
      likely occurs through a diacylglycerol-mediated process that is downstream of
      phosphatidylcholine synthesis.

PMID- 11306572
TI  - Functional analysis of the protein-interacting domains of chloroplast SRP43.
AB  - The chloroplast signal recognition particle (cpSRP) consists of an evolutionarily
      conserved 54-kDa subunit (cpSRP54) and a dimer of a unique 43-kDa subunit
      (cpSRP43). cpSRP binds light-harvesting chlorophyll proteins (LHCPs) to form a
      cpSRP/LHCP transit complex, which targets LHCP to the thylakoid membrane.
      Previous studies showed that transit complex formation is mediated through the
      binding of the L18 domain of LHCP to cpSRP43. cpSRP43 is characterized by a four
      ankyrin repeat domain at the N terminus and two chromodomains at the C terminus.
      In the present study we used the yeast two-hybrid system and in vitro binding
      assays to analyze the function of different domains of cpSRP43 in protein complex
      formation. We report here that the first ankyrin repeat binds to the 18-amino
      acid domain on LHCP that binds to cpSRP43, whereas the third and fourth ankyrin
      repeats are involved in the dimerization of cpSRP43. We show further that the
      interaction of cpSRP43 with cpSRP54 is mediated via binding of the methionine
      rich domain of cpSRP54 to the C-terminally located chromodomains of cpSRP43. Both
      chromodomains contain essential elements for binding cpSRP54, indicating that the
      closely spaced chromodomains together create a single binding site for cpSRP54.
      In addition, our data demonstrate that the interaction of cpSRP54 with the
      chromodomains of cpSRP43 is enhanced indirectly by the dimerization motif of
      cpSRP43.

PMID- 11306573
TI  - Activation of calcium/calmodulin-dependent protein kinase IV in long term
      potentiation in the rat hippocampal CA1 region.
AB  - The importance of well characterized calcium/calmodulin-dependent protein kinase
      (CaMK) II in hippocampal long term potentiation (LTP) is widely well established;
      however, several CaMKs other than CaMKII are not yet clearly characterized and
      understood. Here we report the activation of CaMKIV, which is phosphorylated by
      CaMK kinase and localized predominantly in neuronal nuclei, and its functional
      role as a cyclic AMP-responsive element-binding protein (CREB) kinase in high
      frequency stimulation (HFS)-induced LTP in the rat hippocampal CA1 region. CaMKIV
      was transiently activated in neuronal nuclei after HFS, and the activation
      returned to the basal level within 30 min. Phosphorylation of CREB, which is a
      CaMKIV substrate, and expression of c-Fos protein, which is regulated by CREB,
      increased during LTP. This increase was inhibited mainly by CaMK inhibitors and
      also by an inhibitor for mitogen-activated protein kinase cascade, although to a
      lesser extent. Our results suggest that CaMKIV functions as a CREB kinase and
      controls CREB-regulated gene expression during HFS-induced LTP in the rat
      hippocampal CA1 region.

PMID- 11306574
TI  - A novel pathway of aerobic benzoate catabolism in the bacteria Azoarcus evansii
      and Bacillus stearothermophilus.
AB  - The aerobic catabolism of benzoate was studied in the Gram-negative
      proteobacterium Azoarcus evansii and in the Gram-positive bacterium Bacillus
      stearothermophilus. In contrast to earlier proposals, benzoate was not converted
      into hydroxybenzoate or gentisate. Rather, benzoyl-CoA was a product of benzoate
      catabolism in both microbial species under aerobic conditions in vivo. Benzoyl
      CoA was converted into various CoA thioesters by cell extracts of both species in
      oxygen- and NADPH-dependent reactions. Using [ring-(13)C(6)]benzoyl-CoA as
      substrate, cis-3,4-[2,3,4,5,6-(13)C(5)]dehydroadipyl-CoA, trans-2,3-[2,3,4,5,6
      (13)C(5)]dehydroadipyl-CoA, the 3,6-lactone of 3-[2,3,4,5,6
      (13)C(5)]hydroxyadipyl-CoA, and 3-[2,3,4,5,6-(13)C(5)]hydroxyadipyl-CoA were
      identified as products by NMR spectroscopy. A protein mixture of A. evansii
      transformed [ring-(13)C(6)]benzoyl-CoA in an NADPH- and oxygen-dependent reaction
      into 6-[2,3,4,5,6-(13)C(5)]hydroxy-3-hexenoyl-CoA. The data suggest a novel
      aerobic pathway of benzoate catabolism via CoA intermediates leading to beta
      ketoadipyl-CoA, an intermediate of the known beta-ketoadipate pathway.

PMID- 11306575
TI  - The EMAPII cytokine is released from the mammalian multisynthetase complex after
      cleavage of its p43/proEMAPII component.
AB  - Endothelial-monocyte-activating polypeptide II (EMAPII) is an inflammatory
      cytokine released under apoptotic conditions. Its proEMAPII precursor proved to
      be identical to the auxiliary p43 component of the aminoacyl-tRNA synthetase
      complex. We show here that the EMAPII domain of p43 is released readily from the
      complex after in vitro digestion with caspase 7 and is able to induce migration
      of human mononuclear phagocytes. The N terminus of in vitro-processed EMAPII
      coincides exactly with that of the mature cytokine isolated from conditioned
      medium of fibrosarcoma cells. We also show that p43/proEMAPII has a strong tRNA
      binding capacity (K(D) = 0.2 microm) as compared with its isolated N or C domains
      (7.5 microm and 40 microm, respectively). The potent general RNA binding capacity
      ascribed to p43/proEMAPII is lost upon the release of the EMAPII domain. This
      suggests that after onset of apoptosis, the first consequence of the cleavage of
      p43 is to limit the availability of tRNA for aminoacyl-tRNA synthetases
      associated within the complex. Translation arrest is accompanied by the release
      of the EMAPII cytokine that plays a role in the engulfment of apoptotic cells by
      attracting phagocytes. As a consequence, p43 compares well with a molecular fuse
      that triggers the irreversible cell growth/cell death transition induced under
      apoptotic conditions.

PMID- 11306576
TI  - Tetramer dissociation and monomer partial unfolding precedes protofibril
      formation in amyloidogenic transthyretin variants.
AB  - Amyloid fibril formation and deposition is a common feature of a wide range of
      fatal diseases including spongiform encephalopathies, Alzheimer's disease, and
      familial amyloidotic polyneuropathies (FAP), among many others. In certain forms
      of FAP, the amyloid fibrils are mostly constituted by variants of transthyretin
      (TTR), a homotetrameric plasma protein. Recently, we showed that transthyretin in
      solution may undergo dissociation to a non-native monomer, even under close to
      physiological conditions of temperature, pH, ionic strength, and protein
      concentration. We also showed that this non-native monomer is a compact
      structure, does not behave as a molten globule, and may lead to the formation of
      partially unfolded monomeric species and high molecular mass soluble aggregates
      (Quintas, A., Saraiva, M. J. M., and Brito, R. M. M. (1999) J. Biol. Chem. 274,
      32943-32949). Here, based on aging experiments of tetrameric TTR and chemically
      induced protein unfolding experiments of the non-native monomeric forms, we show
      that tetramer dissociation and partial unfolding of the monomer precedes amyloid
      fibril formation. We also show that TTR variants with the least thermodynamically
      stable non-native monomer produce the largest amount of partially unfolded
      monomeric species and soluble aggregates under conditions that are close to
      physiological. Additionally, the soluble aggregates formed by the amyloidogenic
      TTR variants showed morphological and thioflavin-T fluorescence properties
      characteristic of amyloid. These results allowed us to conclude that amyloid
      fibril formation by some TTR variants might be triggered by tetramer dissociation
      to a compact non-native monomer with low conformational stability, which
      originates partially unfolded monomeric species with a high tendency for ordered
      aggregation into amyloid fibrils. Thus, partial unfolding and conformational
      fluctuations of molecular species with marginal thermodynamic stability may play
      a crucial role on amyloid formation in vivo.

PMID- 11306577
TI  - Transcription repression of human hepatitis B virus genes by negative regulatory
      element-binding protein/SON.
AB  - A negative regulatory element (NRE) is located immediately upstream of the
      upstream regulatory sequence of core promoter and second enhancer of human
      hepatitis B virus (HBV). NRE represses the transcription activation function of
      the upstream regulatory sequence of core promoter and the second enhancer. In
      this study, we described the cloning and characterization of an NRE-binding
      protein (NREBP) through expression cloning. NREBP cDNA is 8266 nucleotides in
      size and encodes a protein of 2386 amino acids with a predicted molecular mass of
      262 kDa. Three previously described cDNAs, DBP-5, SONB, and SONA, are partial
      sequence and/or alternatively spliced forms of NREBP. The genomic locus of the
      NREBP/SON gene is composed of 13 exons and 12 introns. The endogenous NREBP
      protein is localized in the nucleus of human hepatoma HuH-7 cells. Antibody
      against NREBP protein can specifically block the NRE binding activity present in
      fractionated nuclear extracts in gel shifting assays, indicating that NREBP is
      the endogenous nuclear protein that binds to NRE sequence. By polymerase chain
      reaction-assisted binding site selection assay, we determined that the consensus
      sequence for NREBP binding is GA(G/T)AN(C/G)(A/G)CC. Overexpression of NREBP
      enhances the repression of the HBV core promoter activity via NRE. Overexpression
      of NREBP can also repress the transcription of HBV genes and the production of
      HBV virions in a transient transfection system that mimics the viral infection in
      vivo.

PMID- 11306578
TI  - Disruption of imprinted expression of U2afbp-rs/U2af1-rs1 gene in mouse
      parthenogenetic fetuses.
AB  - The present study shows that the U2afbp-rs gene, a paternally expressed imprinted
      gene, is activated and expressed in a biallelic manner from maternal alleles in
      parthenogenetic mouse fetuses on day 9.5 of gestation. The mean expression was
      detected to be 88% (31-134%) of that in control biparental fetuses, using real
      time quantitative reverse transcription and polymerase chain reaction. This
      disrupted expression of the gene was associated with changes in the chromatin
      structure but not with the methylation pattern in the regulation region. The
      present results show that parental specific expression of imprinted genes is not
      always maintained in uniparental embryos. This suggests that both parental
      genomes are necessary to establish parental specific expression of the U2afbp-rs
      gene.

PMID- 11306579
TI  - HSP-CBF is an NF-Y-dependent coactivator of the heat shock promoters CCAAT boxes.
AB  - The cellular response to toxic stimuli is elicited through the expression of heat
      shock proteins, a transcriptional process that relies upon conserved DNA elements
      in the promoters: the Heat Shock Elements, activated by the heat shock factors,
      and the CCAAT boxes. The identity of the CCAAT activator(s) is unclear because
      two distinct entities, NF-Y and HSP-CBF, have been implicated in the HSP70
      system. The former is a conserved ubiquitous trimer containing histone-like
      subunits, the latter a 110-kDa protein with an acidic N-terminal. We analyzed two
      CCAAT-containing promoters, HSP70 and HSP40, with recombinant NF-Y and HSP-CBF
      using electrophoretic mobility shift assay, protein-protein interactions,
      transfections and chromatin immunoprecipitation assays (ChIP) assays. Both
      recognize a common DNA-binding protein in nuclear extracts, identified in vitro
      and in vivo as NF-Y. Both CCAAT boxes show high affinity for recombinant NF-Y but
      not for HSP-CBF. However, HSP-CBF does activate HSP70 and HSP40 transcription
      under basal and heat shocked conditions; for doing so, it requires an intact NF-Y
      trimer as judged by cotransfections with a diagnostic NF-YA dominant negative
      vector. HSP-CBF interacts in solution and on DNA with the NF-Y trimer through an
      evolutionary conserved region. In yeast two-hybrid assays HSP-CBF interacts with
      NF-YB. These data implicate HSP-CBF as a non-DNA binding coactivator of heat
      shock genes that act on a DNA-bound NF-Y.

PMID- 11306580
TI  - Dynamin and Rab5a-dependent trafficking and signaling of the neurokinin 1
      receptor.
AB  - Understanding the molecular mechanisms of agonist-induced trafficking of G
      protein-coupled receptors is important because of the essential role of
      trafficking in signal transduction. We examined the role of the GTPases dynamin 1
      and Rab5a in substance P (SP)-induced trafficking and signaling of the neurokinin
      1 receptor (NK1R), an important mediator of pain, depression, and inflammation,
      by studying transfected cells and enteric neurons that naturally express the
      NK1R. In unstimulated cells, the NK1R colocalized with dynamin at the plasma
      membrane, and Rab5a was detected in endosomes. SP induced translocation of the
      receptor into endosomes containing Rab5a immediately beneath the plasma membrane
      and then in a perinuclear location. Expression of the dominant negative mutants
      dynamin 1 K44E and Rab5aS34N inhibited endocytosis of SP by 45 and 32%,
      respectively. Dynamin K44E caused membrane retention of the NK1R, whereas
      Rab5aS34N also impeded the translocation of the receptor from superficially
      located to perinuclear endosomes. Both dynamin K44E and Rab5aS34N strongly
      inhibited resensitization of SP-induced Ca(2+) mobilization by 60 and 85%,
      respectively, but had no effect on NK1R desensitization. Dynamin K44E but not
      Rab5aS34N markedly reduced SP-induced phosphorylation of extracellular signal
      regulated kinases 1 and 2. Thus, dynamin mediates the formation of endosomes
      containing the NK1R, and Rab5a mediates both endosomal formation and their
      translocation from a superficial to a perinuclear location. Dynamin and Rab5a
      dependent trafficking is essential for NK1R resensitization but is not necessary
      for desensitization of signaling. Dynamin-dependent but not Rab5a-dependent
      trafficking is required for coupling of the NK1R to the mitogen-activated protein
      kinase cascade. These processes may regulate the nociceptive, depressive, and
      proinflammatory effects of SP.

PMID- 11306581
TI  - Astrocytes regulate N-methyl-D-aspartate receptor subunit composition increasing
      neuronal sensitivity to excitotoxicity.
AB  - We have examined the dependence of rat cerebellar granule neurons (CGNs) for
      protection against glutamate toxicity. Under co-culture conditions, rat CGNs
      require astrocytes to protect against glutamate. The CGNs become more sensitive
      to glutamate toxicity in co-culture than when grown in cultures with only low
      numbers of astrocytes. If the protection of the astrocytes was withdrawn or
      blocked, this sensitivity led to neuronal death. Differing changes in NMDA
      receptor subunit subtype composition were noted depending on the conditions in
      which the CGNs were grown. Suppression of individual NMDA subunit subtypes by
      oligonucleotide knockdown resulted in inhibition of toxicity. This result implies
      that astrocytes regulate the expression of NMDA receptor subunit subtypes which
      influence neuronal sensitivity to glutamate toxicity.

PMID- 11306582
TI  - Cathepsin S regulates the expression of cathepsin L and the turnover of gamma
      interferon-inducible lysosomal thiol reductase in B lymphocytes.
AB  - Loading of antigenic peptide fragments on major histocompatibility complex class
      II molecules is essential for generation of CD4(+) T cell responses and occurs
      after cathepsin-mediated degradation of the invariant chain chaperone molecule.
      Cathepsins are expressed differentially in antigen presenting cells, and mice
      deficient in cathepsin S or cathepsin L exhibit severely impaired antigen
      presentation in peripheral lymphoid organs and the thymus, respectively. To
      determine whether these defects are due solely to the block in invariant chain
      cleavage, we used cathepsin-deficient B cells to examine the role of cathepsins S
      and B in the degradation of other molecules important in the class II
      presentation pathway. Our data indicate that neither cathepsin S nor B is
      critical for H-2M degradation or processing of precursor gamma-interferon
      inducible lysosomal thiol reductase (GILT) to a mature thiol reductase, but
      suggest a role for cathepsin S in the turnover of mature GILT and in regulating
      levels of mature cathepsin L protein in B cells. Despite the presence of mature
      cathepsin L protein, no enzyme activity could be detected in B cells or dendritic
      cells. These experiments suggest a novel mechanism by which these functionally
      important enzymes may be regulated.

PMID- 11306583
TI  - Mechanism of Inhibition of beta-site amyloid precursor protein-cleaving enzyme
      (BACE) by a statine-based peptide.
AB  - Inhibition of beta-site amyloid precursor protein-cleaving enzyme by a statine
      based inhibitor has been studied using steady state and stopped-flow methods. A
      slow onset rate of inhibition has been observed under steady state conditions,
      and a K(i) of 22 nm has been derived using progress curves analysis. Simulation
      of stopped-flow protein fluorescence transients provided an estimate of the K(d)
      for initial inhibitor binding of 660 nm. A two-step inhibition mechanism is
      proposed, wherein slower "tightening up" of the initial encounter complex occurs.
      Two hypotheses have been proposed in the literature to address the nature of the
      slow step in the inhibition of aspartic proteases by peptidomimetic inhibitors: a
      conformational change related to the "flap" movement and displacement of a
      catalytic water. We compared substrate and inhibitor binding rates under pre
      steady-state conditions. Both ligands are likely to cause flap movement, whereas
      no catalytic water replacement occurs during substrate binding. Our results
      suggest that both ligands bind to the enzyme at a rate significantly lower than
      the diffusion limit, but there are additional rate limitations involved in
      inhibitor binding, resulting in a k(on) of 3.5 x 10(4) m(-)1 s(-)1 for the
      inhibitor compared with 3.5 x 10(5) m(-)1 s(-)1 for the substrate. Even though
      specific intermediate formation steps might be different in the productive
      inhibitor and substrate binding to beta-site amyloid precursor protein-cleaving
      enzyme, a similar final optimized conformation is achieved in both cases, as
      judged by the comparable free energy changes (DeltaDeltaG of 2.01 versus 1.97
      kcal/mol) going from the initial to the final enzyme-inhibitor or enzyme
      substrate complexes.

PMID- 11306584
TI  - A CD45 polymorphism associated with multiple sclerosis disrupts an exonic
      splicing silencer.
AB  - Previous studies have identified a single nucleotide polymorphism that
      significantly increases the splicing of variable exon 4 in transcripts of the
      human protein-tyrosine phosphatase CD45. Strikingly, the presence of this
      polymorphism correlates with susceptibility to the autoimmune disease multiple
      sclerosis. In this study we investigated the mechanism by which the polymorphism
      enhances splicing of CD45 exon 4. We found that at least four distinct splicing
      regulatory elements exist within exon 4 and that the strongest of these elements
      is an exonic splicing silencer (designated ESS1), which is disrupted by the
      polymorphism. We show that ESS1 normally functions to repress the weak 5' splice
      site (ss) of CD45 exon 4. The ESS1 sequence also suppresses the splicing of a
      heterologous 5'ss and associates with a specific complex in nuclear extracts. We
      further demonstrate that ESS1 is juxtaposed to a purine-rich enhancer sequence
      that activates the use of the 5'ss of exon 4. Thus, proper functioning of the
      immune system is dependent on a complex interplay of regulatory activities that
      mediate the appropriate splicing of CD45 exon 4.

PMID- 11306585
TI  - Pho23 is associated with the Rpd3 histone deacetylase and is required for its
      normal function in regulation of gene expression and silencing in Saccharomyces
      cerevisiae.
AB  - The Rpd3 histone deacetylase (HDAC) functions in a large complex containing many
      proteins including Sin3 and Sap30. Previous evidence indicates that the pho23,
      rpd3, sin3, and sap30 mutants exhibit similar defects in PHO5 regulation. We
      report that pho23 mutants like rpd3, sin3, and sap30 are hypersensitive to
      cycloheximide and heat shock and exhibit enhanced silencing of rDNA, telomeric,
      and HMR loci, suggesting that these genes are functionally related. Based on
      these observations, we explored whether Pho23 is a component of the Rpd3 HDAC
      complex. Our results demonstrate that Myc-Pho23 co-immunoprecipitates with HA
      Rpd3 and HA-Sap30. Furthermore, similar levels of HDAC activity were detected in
      immunoprecipitates of HA-Pho23, HA-Rpd3, or HA-Sap30. In contrast, HDAC activity
      was not detected in immunoprecipitates of HA-Pho23 or HA-Sap30 from strains
      lacking Rpd3, suggesting that Rpd3 is the HDAC associated with these proteins.
      However, HDAC activity was detected in immunoprecipitates of HA-Sap30 or HA-Rpd3
      from cells lacking Pho23, although levels were significantly lower than those
      detected in wild-type cells, indicating that Rpd3 activity is compromised in the
      absence of Pho23. Together, our genetic and biochemical studies provide strong
      evidence that Pho23 is a component of the Rpd3 HDAC complex, and is required for
      the normal function of this complex.

PMID- 11306586
TI  - Contribution of the bacterial endosymbiont to the biosynthesis of pyrimidine
      nucleotides in the deep-sea tube worm Riftia pachyptila.
AB  - The deep-sea tube worm Riftia pachyptila (Vestimentifera) from hydrothermal vents
      lives in an intimate symbiosis with a sulfur-oxidizing bacterium. That involves
      specific interactions and obligatory metabolic exchanges between the two
      organisms. In this work, we analyzed the contribution of the two partners to the
      biosynthesis of pyrimidine nucleotides through both the "de novo" and "salvage"
      pathways. The first three enzymes of the de novo pathway, carbamyl-phosphate
      synthetase, aspartate transcarbamylase, and dihydroorotase, were present only in
      the trophosome, the symbiont-containing tissue. The study of these enzymes in
      terms of their catalytic and regulatory properties in both the trophosome and the
      isolated symbiotic bacteria provided a clear indication of the microbial origin
      of these enzymes. In contrast, the succeeding enzymes of this de novo pathway,
      dihydroorotate dehydrogenase and orotate phosphoribosyltransferase, were present
      in all body parts of the worm. This finding indicates that the animal is fully
      dependent on the symbiont for the de novo biosynthesis of pyrimidines. In
      addition, it suggests that the synthesis of pyrimidines in other tissues is
      possible from the intermediary metabolites provided by the trophosomal tissue and
      from nucleic acid degradation products since the enzymes of the salvage pathway
      appear to be present in all tissues of the worm. Analysis of these salvage
      pathway enzymes in the trophosome strongly suggested that these enzymes belong to
      the worm. In accordance with this conclusion, none of these enzyme activities was
      found in the isolated bacteria. The enzymes involved in the production of the
      precursors of carbamyl phosphate and nitrogen assimilation, glutamine synthetase
      and nitrate reductase, were also investigated, and it appears that these two
      enzymes are present in the bacteria.

PMID- 11306587
TI  - Stalk segment 5 of the yeast plasma membrane H+-ATPase: mutational evidence for a
      role in glucose regulation.
AB  - In P(2)-type ATPases, a stalk region connects the cytoplasmic part of the
      molecule, which binds and hydrolyzes ATP, to the membrane-embedded part through
      which cations are pumped. The present study has used cysteine scanning
      mutagenesis to examine structure-function relationships within stalk segment 5
      (S5) of the yeast plasma-membrane H(+)-ATPase. Of 29 Cys mutants that were made
      and examined, two (G670C and R682C) were blocked in biogenesis, presumably due to
      protein misfolding. In addition, one mutant (S681C) had very low ATPase activity,
      and another (F685C) displayed a 40-fold decrease in sensitivity to orthovanadate,
      reflecting a shift in equilibrium from the E(2) conformational state toward E(1).
      By far the most striking group of mutants (F666C, L671C, I674C, A677C, I684C,
      R687C, and Y689C) were constitutively activated even in the absence of glucose,
      with rates of ATP hydrolysis and kinetic properties normally seen only in glucose
      metabolizing cells. Previous work has suggested that activation of the wild-type
      H(+)-ATPase results from kinase-mediated phosphorylation in the auto-inhibitory C
      terminal region of the 100-kDa polypeptide. The seven residues identified in the
      present study are located on one face of the S5 alpha-helix, consistent with the
      idea that mutations along this face serve to release the auto-inhibition.

PMID- 11306588
TI  - The Leishmania ATP-binding cassette protein PGPA is an intracellular metal-thiol
      transporter ATPase.
AB  - The Leishmania ATP-binding cassette (ABC) transporter PGPA is involved in metal
      resistance (arsenicals and antimony), although the exact mechanism by which PGPA
      confers resistance to antimony, the first line drug against Leishmania, is
      unknown. The results of co-transfection experiments, transport assays, and the
      use of inhibitors suggest that PGPA recognizes metals conjugated to glutathione
      or trypanothione, a glutathione-spermidine conjugate present in Leishmania. The
      HA epitope tag of the influenza hemagglutinin as well as the green fluorescent
      protein were fused at the COOH terminus of PGPA. Immunofluorescence, confocal,
      and electron microscopy studies of the fully functional tagged molecules clearly
      indicated that PGPA is localized in membranes that are close to the flagellar
      pocket, the site of endocytosis and exocytosis in this parasite. Subcellular
      fractionation of Leishmania tarentolae PGPAHA transfectants was performed to
      further characterize this ABC transporter. The basal PGPA ATPase activity was
      determined to be 115 nmol/mg/min. Transport experiments using radioactive
      arsenite-glutathione conjugates clearly showed that PGPA recognizes and actively
      transports thiol-metal conjugates. Overall, the results are consistent with PGPA
      being an intracellular ABC transporter that confers arsenite and antimonite
      resistance by sequestration of the metal-thiol conjugates.

PMID- 11306589
TI  - Translational repression and specific RNA binding by the coat protein of the
      Pseudomonas phage PP7.
AB  - PP7 is a single-strand RNA bacteriophage of Pseudomonas aeroginosa and a distant
      relative to coliphages like MS2 and Qbeta. Here we show that PP7 coat protein is
      a specific RNA-binding protein, capable of repressing the translation of
      sequences fused to the translation initiation region of PP7 replicase. Its RNA
      binding activity is specific since it represses the translational operator of
      PP7, but does not repress the operators of the MS2 or Qbeta phages. Conditions
      for the purification of coat protein and for the reconstitution of its RNA
      binding activity from disaggregated virus-like particles were established. Its
      dissociation constant for PP7 operator RNA in vitro was determined to be about 1
      nm. Using a genetic system in which coat protein represses translation of a
      replicase-beta-galactosidase fusion protein, amino acid residues important for
      binding of PP7 RNA were identified.

PMID- 11306590
TI  - Identification of apocalmodulin and Ca2+-calmodulin regulatory domain in skeletal
      muscle Ca2+ release channel, ryanodine receptor.
AB  - Fusion proteins and full-length mutants were generated to identify the Ca(2+)
      free (apoCaM) and Ca(2+)-bound (CaCaM) calmodulin binding sites of the skeletal
      muscle Ca(2+) release channel/ryanodine receptor (RyR1). [(35)S]Calmodulin (CaM)
      overlays of fusion proteins revealed one potential Ca(2+)-dependent (aa 3553
      3662) and one Ca(2+)-independent (aa 4302-4430) CaM binding domain. W3620A or
      L3624D substitutions almost abolished completely, whereas V3619A or L3624A
      substitutions reduced [(35)S]CaM binding to fusion protein (aa 3553-3662). Three
      full-length RyR1 single-site mutants (V3619A,W3620A,L3624D) and one deletion
      mutant (Delta4274-4535) were generated and expressed in human embryonic kidney
      293 cells. L3624D exhibited greatly reduced [(35)S]CaM binding affinity as
      indicated by a lack of noticeable binding of apoCaM and CaCaM (nanomolar) and the
      requirement of CaCaM (micromolar) for the inhibition of RyR1 activity. W3620A
      bound CaM (nanomolar) only in the absence of Ca(2+) and did not show inhibition
      of RyR1 activity by 3 microm CaCaM. V3619A and the deletion mutant bound apoCaM
      and CaCaM at levels compared with wild type. V3619A activity was inhibited by CaM
      with IC(50) approximately 200 nm, as compared with IC(50) approximately 50 nm for
      wild type and the deletion mutant. [(35)S]CaM binding experiments with
      sarcoplasmic reticulum vesicles suggested that apoCaM and CaCaM bind to the same
      region of the native RyR1 channel complex. These results indicate that the intact
      RyR1 has a single CaM binding domain that is shared by apoCaM and CaCaM.

PMID- 11306591
TI  - Suppressor of cytokine signaling-1 attenuates the duration of interferon gamma
      signal transduction in vitro and in vivo.
AB  - Suppressor of cytokine signaling-1 (SOCS-1) is a cytokine-inducible intracellular
      protein that functions to negatively regulate cytokine signal transduction
      pathways. Studies in vitro have shown that constitutive overexpression of SOCS-1
      inhibits signaling in response to a range of cytokines, including interferons
      (IFN). Mice lacking SOCS-1 die from a complex disease characterized by liver
      degeneration and massive inflammation. Whereas there is clear evidence of
      increased IFNgamma signaling in SOCS-1(-/-) mice, it is unclear to what extent
      this is due to increased IFNgamma levels or to increased IFNgamma sensitivity.
      Here we have used SOCS-1(-/-) IFNgamma(-/-) mice, which remain healthy and
      produce no endogenous IFNgamma, to demonstrate that in vitro and in vivo
      hepatocytes lacking SOCS-1 exhibit a prolonged response to IFNgamma and that this
      correlates with a dramatically increased sensitivity to the toxic effects of
      IFNgamma in vivo. Thus, SOCS-1 is required for the timely attenuation of IFNgamma
      signaling in vivo.

PMID- 11306592
TI  - Functional mapping of destabilizing elements in the protein-coding region of the
      Drosophila fushi tarazu mRNA.
AB  - The instability of the fushi tarazu (ftz) mRNA is essential for the proper
      development of the Drosophila embryo. Previously, we identified a 201-nucleotide
      instability element (FIE3) in the 3' untranslated region (UTR) of the ftz mRNA.
      Here we report on the identification of two additional elements in the protein
      coding region of the message: the 63-nucleotide-long FIE5-1 and the 69-nucleotide
      long FIE5-2. The function of both elements was position-dependent; the same
      elements destabilized RNAs when present within the coding region but did not when
      embedded in the 3' UTR of the hybrid mRNAs. We conclude that ftz mRNA has three
      redundant instability elements, two in the protein-coding region and one in the
      3' UTR. Although each instability element is sufficient to destabilize a
      heterologous mRNA, the destabilizing activity of the two 5'-elements depended on
      their position within the message.

PMID- 11306594
TI  - Syndecans: transmembrane modulators of adhesion and matrix assembly.

PMID- 11306593
TI  - Thrombospondins as matricellular modulators of cell function.

PMID- 11306595
TI  - Infection, mimics, and autoimmune disease.

PMID- 11306596
TI  - More weapons in the arsenal against ischemic retinopathy.

PMID- 11306597
TI  - Beta-adrenergic receptors in the failing heart: the good, the bad, and the
      unknown.

PMID- 11306598
TI  - Expression of IL-5 alters bone metabolism and induces ossification of the spleen
      in transgenic mice.
AB  - We have developed a transgenic mouse line, NJ.1638, which expresses high levels
      of IL-5 from T cells, with profound hematological consequences. Eosinophils
      comprise more than 60% of circulating white blood cells in these animals, with
      the total peripheral white blood cell counts increasing more than 40-fold
      relative to wild-type littermates. This extraordinary proliferative capacity is
      sustained by expanded sites of extramedullary hematopoiesis and is accompanied by
      multifocal, ectopic bone formation in the spleen. Histology of the splenic
      nodules revealed the presence of osteoid matrices and osteocytes trapped within
      mineralized trabecular plates. In addition, polarized light microscopy of
      calcified tissue sections revealed both woven bone and areas of organized
      lamellar bone. Morphometric assessments demonstrated that both the growth and
      mineralization of splenic bone occurred at rates nearly an order of magnitude
      higher than in skeletal bone. Skeletal bone metabolic parameters were also
      perturbed. We also observed heterotopic ossification of the spleen and
      perturbation of skeletal bone homeostasis following adoptive engraftment of
      transgenic marrow to wild-type recipients. These data suggest that IL-5
      overexpression mediates bone formation through the mobilization of marrow-derived
      osteogenic progenitors and/or the inhibition of recruited osteoclasts.

PMID- 11306599
TI  - Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice.
AB  - Targeted ablation of the vitamin D receptor (VDR) results in hypocalcemia,
      hypophosphatemia, hyperparathyroidism, rickets, osteomalacia, and alopecia--the
      last a consequence of defective anagen initiation. To investigate whether the
      markedly elevated levels of 1,25-dihydroxyvitamin D led to the alopecia, we
      raised VDR-null mice in a ultraviolet light-free environment and fed them chow
      lacking vitamin D for five generations. Despite undetectable circulating levels
      of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, alopecia persisted in the VDR
      null mice, demonstrating that the alopecia was not secondary to toxic levels of
      1,25-dihydroxyvitamin D interacting with an alternative receptor. Furthermore,
      alopecia was not seen in control littermates, suggesting that absence of ligand
      and absence of receptor cause different phenotypes. To identify the cell
      population responsible for the alopecia, we performed hair-reconstitution assays
      in nude mice and observed normal hair follicle morphogenesis, regardless of the
      VDR status of the keratinocytes and dermal papilla cells. However, follicles
      reconstituted with VDR-null keratinocytes demonstrated a defective response to
      anagen initiation. Hence, alopecia in the VDR-null mice is due to a defect in
      epithelial-mesenchymal communication that is required for normal hair cycling.
      Our results also identify the keratinocyte as the cell of origin of the defect
      and suggest that this form of alopecia is due to absence of ligand-independent
      receptor function.

PMID- 11306600
TI  - Alterations in cardiac adrenergic signaling and calcium cycling differentially
      affect the progression of cardiomyopathy.
AB  - The medical treatment of chronic heart failure has undergone a dramatic
      transition in the past decade. Short-term approaches for altering hemodynamics
      have given way to long-term, reparative strategies, including beta-adrenergic
      receptor (betaAR) blockade. This was once viewed as counterintuitive, because
      acute administration causes myocardial depression. Cardiac myocytes from failing
      hearts show changes in betaAR signaling and excitation-contraction coupling that
      can impair cardiac contractility, but the role of these abnormalities in the
      progression of heart failure is controversial. We therefore tested the impact of
      different manipulations that increase contractility on the progression of cardiac
      dysfunction in a mouse model of hypertrophic cardiomyopathy. High-level
      overexpression of the beta(2)AR caused rapidly progressive cardiac failure in
      this model. In contrast, phospholamban ablation prevented systolic dysfunction
      and exercise intolerance, but not hypertrophy, in hypertrophic cardiomyopathy
      mice. Cardiac expression of a peptide inhibitor of the betaAR kinase 1 not only
      prevented systolic dysfunction and exercise intolerance but also decreased
      cardiac remodeling and hypertrophic gene expression. These three manipulations of
      cardiac contractility had distinct effects on disease progression, suggesting
      that selective modulation of particular aspects of betaAR signaling or excitation
      contraction coupling can provide therapeutic benefit.

PMID- 11306601
TI  - Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide
      receptor A-deficient mice.
AB  - Mice lacking natriuretic peptide receptor A (NPRA) have marked cardiac
      hypertrophy and chamber dilatation disproportionate to their increased blood
      pressure (BP), suggesting, in support of previous in vitro data, that the NPRA
      system moderates the cardiac response to hypertrophic stimuli. Here, we have
      followed the changes in cardiac function in response to altered mechanical load
      on the heart of NPRA-null mice (Npr1-/-). Chronic treatment with either
      enalapril, furosemide, hydralazine, or losartan were all effective in reducing
      and maintaining BP at normal levels without affecting heart weight/body weight.
      In the reverse direction, we used transverse aortic constriction (TAC) to induce
      pressure overload. In the Npr1-/- mice, TAC resulted in a 15-fold increase in
      atrial natriuretic peptide (ANP) expression, a 55% increase in left ventricular
      weight/body weight (LV/BW), dilatation of the LV, and significant decline in
      cardiac function. In contrast, banded Npr1+/+ mice showed only a threefold
      increase in ANP expression, an 11% increase in LV/BW, a 0.2 mm decrease in LV end
      diastolic dimension, and no change in fractional shortening. The activation of
      mitogen-activated protein kinases that occurs in response to TAC did not differ
      in the Npr1+/+ and Npr1-/- mice. Taken together, these results suggest that the
      NPRA system has direct antihypertrophic actions in the heart, independent of its
      role in BP control.

PMID- 11306602
TI  - Dominant T- and B-cell epitopes in an autoantigen linked to Chagas' disease.
AB  - In Chagas' disease caused by Trypanosoma cruzi, a paradigm of autoimmune disease,
      both autoantibodies and autoreactive T cells have been described. We have
      identified a novel dominant autoantigen, named Cha, recognized by the majority of
      sera from T. cruzi-infected humans and mice. We noted significant homologies
      between amino acids 120-129 of Cha, where the B-cell epitope maps, and an
      expressed sequence tag from T. cruzi, and also between amino acids 254-273 of Cha
      and a repeated amino acid sequence from the shed acute-phase antigen (SAPA) of T.
      cruzi. Moreover, T. cruzi-infected mice contain autoreactive T cells that can
      cross-react with Cha and the SAPA homologous peptides. Transfer of T cells from
      infected mice triggered anti-Cha (120-129) Ab production in naive recipients.
      Interestingly, heart tissue sections from those adoptive transferred mice showed
      cardiac pathology similar to T. cruzi-infected mice. Our results demonstrate the
      presence of both T- and B-cell cross-reactive epitopes in the Cha antigen. This
      dual mimicry may lead to T/B cell cooperation and give rise to a pathological
      immunodominant response against Cha in T. cruzi infected animals.

PMID- 11306603
TI  - Discordant effects of anti-VLA-4 treatment before and after onset of relapsing
      experimental autoimmune encephalomyelitis.
AB  - Initial migration of encephalitogenic T cells to the central nervous system (CNS)
      in relapsing experimental autoimmune encephalomyelitis (R-EAE), an animal model
      of multiple sclerosis (MS), depends on the interaction of the alpha4 integrin
      (VLA-4) expressed on activated T cells with VCAM-1 expressed on activated
      cerebrovascular endothelial cells. Alternate homing mechanisms may be employed by
      infiltrating inflammatory cells after disease onset. We thus compared the ability
      of anti-VLA-4 to regulate proteolipid protein (PLP) 139-151-induced R-EAE when
      administered either before or after disease onset. Preclinical administration of
      anti-VLA-4 either to naive recipients of primed encephalitogenic T cells or to
      mice 1 week after peptide priming, i.e., before clinical disease onset, inhibited
      the onset and severity of clinical disease. In contrast, Ab treatment either at
      the peak of acute disease or during remission exacerbated disease relapses and
      increased the accumulation of CD4(+) T cells in the CNS. Most significantly, anti
      VLA-4 treatment either before or during ongoing R-EAE enhanced Th1 responses to
      both the priming peptide and endogenous myelin epitopes released secondary to
      acute tissue damage. Collectively, these results suggest that treatment with anti
      VLA-4 Ab has multiple effects on the immune system and may be problematic in
      treating established autoimmune diseases such as MS.

PMID- 11306604
TI  - Fetal parathyroids are not required to maintain placental calcium transport.
AB  - We used Hoxa3 knockout mice and other mouse models to study the role of the fetal
      parathyroids in fetal calcium homeostasis. Hoxa3-null fetuses lack parathyroid
      glands, and absence of parathyroid hormone (PTH) was confirmed with a rodent PTH
      immunoradiometric assay. The ionized calcium level of Hoxa3-null fetuses was
      significantly lower than that of wild-type or heterozygous littermates or of the
      mother. Both the rate of placental calcium transfer and the plasma PTHrP level
      were normal in Hoxa3 mutants and their heterozygous siblings. Because we had
      previously observed an increase in placental calcium transfer in PTH/PTHrP
      receptor 1-null (Pthr1-null) fetuses, we assayed plasma PTHrP in those mice.
      Pthr1-null fetuses had plasma PTHrP levels 11-fold higher than those of their
      littermates. Northern analysis, immunohistochemical, and in situ hybridization
      studies of Pthr1-null fetuses indicated that liver and placenta had increased
      expression of PTHRP: In summary, loss of fetal parathyroids in Hoxa3-null fetuses
      caused marked hypocalcemia but did not alter placental calcium transfer or the
      circulating PTHrP level. The findings in the Pthr1-null fetuses indicate that
      several tissues may contribute to the circulating PTHrP level in fetal mice.

PMID- 11306605
TI  - Critical role for thyroid hormone receptor beta2 in the regulation of
      paraventricular thyrotropin-releasing hormone neurons.
AB  - Thyroid hormone thyroxine (T(4)) and tri-iodothyronine (T(3)) production is
      regulated by feedback inhibition of thyrotropin (TSH) and thyrotropin-releasing
      hormone (TRH) synthesis in the pituitary and hypothalamus when T(3) binds to
      thyroid hormone receptors (TRs) interacting with the promoters of the genes for
      the TSH subunit and TRH. All of the TR isoforms likely participate in the
      negative regulation of TSH production in vivo, but the identity of the specific
      TR isoforms that negatively regulate TRH production are less clear. To clarify
      the role of the TR-beta2 isoform in the regulation of TRH gene expression in the
      hypothalamic paraventricular nucleus, we examined preprothyrotropin-releasing
      hormone (prepro-TRH) expression in mice lacking the TR-beta2 isoform under basal
      conditions, after the induction of hypothyroidism with propylthiouracil, and in
      response to T(3) administration. Prepro-TRH expression was increased in
      hypothyroid wild-type mice and markedly suppressed after T(3) administration. In
      contrast, basal TRH expression was increased in TR-beta2-null mice to levels seen
      in hypothyroid wild-type mice and did not change significantly in response to
      induction of hypothyroidism or T(3) treatment. However, the suppression of TRH
      mRNA expression in response to leptin reduction during fasting was preserved in
      TR-beta2-null mice. Thus TR-beta2 is the key TR isoform responsible for T(3)
      mediated negative-feedback regulation by hypophysiotropic TRH neurons.

PMID- 11306607
TI  - Na+ - and Cl- -coupled active transport of nitric oxide synthase inhibitors via
      amino acid transport system B(0,+).
AB  - Nitric oxide synthase (NOS) inhibitors have therapeutic potential in the
      management of numerous conditions in which NO overproduction plays a critical
      role. Identification of transport systems in the intestine that can mediate the
      uptake of NOS inhibitors is important to assess the oral bioavailability and
      therapeutic efficacy of these potential drugs. Here, we have cloned the Na+ - and
      Cl- -coupled amino acid transport system B(0,+) (ATB(0,+)) from the mouse colon
      and investigated its ability to transport NOS inhibitors. When expressed in
      mammalian cells, ATB(0,+) can transport a variety of zwitterionic and cationic
      amino acids in a Na+ - and Cl- -coupled manner. Each of the NOS inhibitors tested
      compete with glycine for uptake through this transport system. Furthermore, using
      a tritiated analog of the NOS inhibitor N(G)-nitro-L-arginine, we showed that Na+
      - and Cl- -coupled transport occurs via ATB(0,+). We then studied transport of a
      wide variety of NOS inhibitors in Xenopus laevis oocytes expressing the cloned
      ATB(0,+) and found that ATB(0,+) can transport a broad range of zwitterionic or
      cationic NOS inhibitors. These data represent the first identification of an ion
      gradient-driven transport system for NOS inhibitors in the intestinal tract.

PMID- 11306606
TI  - PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null
      mice.
AB  - PPARalpha is a ligand-dependent transcription factor expressed at high levels in
      the liver. Its activation by the drug gemfibrozil reduces clinical events in
      humans with established atherosclerosis, but the underlying mechanisms are
      incompletely defined. To clarify the role of PPARalpha in vascular disease, we
      crossed PPARalpha-null mice with apoE-null mice to determine if the genetic
      absence of PPARalpha affects vascular disease in a robust atherosclerosis model.
      On a high-fat diet, concentrations of atherogenic lipoproteins were higher in
      PPARalpha(-/-)apoE(-/-) than in PPARalpha(+/+)apoE(-/-) mice, due to increased
      VLDL production. However, en face atherosclerotic lesion areas at the aortic
      arch, thoracic aorta, and abdominal aorta were less in PPARalpha-null animals of
      both sexes after 6 and 10 weeks of high-fat feeding. Despite gaining as much or
      more weight than their PPARalpha(+/+)apoE(-/-) littermates, PPARalpha(-/-)apoE(-/
      ) mice had lower fasting levels of glucose and insulin. PPARalpha-null animals
      had greater suppression of endogenous glucose production in hyperinsulinemic
      clamp experiments, reflecting less insulin resistance in the absence of
      PPARalpha. PPARalpha(-/-)apoE(-/-) mice also had lower blood pressures than their
      PPARalpha(+/+)apoE(-/-) littermates after high-fat feeding. These results suggest
      that PPARalpha may participate in the pathogenesis of diet-induced insulin
      resistance and atherosclerosis.

PMID- 11306608
TI  - Calcium-dependent inhibition of L, N, and P/Q Ca2+ channels in chromaffin cells:
      role of mitochondria.
AB  - The hypothesis that the buffering of Ca(2+) by mitochondria could affect the
      Ca(2+)-dependent inhibition of voltage-activated Ca(2+) channels, (I(Ca)), was
      tested in voltage-clamped bovine adrenal chromaffin cells. The protonophore
      carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), the blocker of the Ca(2+)
      uniporter ruthenium red (RR), and a combination of oligomycin plus rotenone were
      used to interfere with mitochondrial Ca(2+) buffering. In cells dialyzed with an
      EGTA-free solution, peak I(Ca) generated by 20 msec pulses to 0 or +10 mV,
      applied at 15 sec intervals, from a holding potential of -80 mV, decayed rapidly
      after superfusion of cells with 2 microm CCCP (tau = 16.7 +/- 3 sec; n = 8). In
      cells dialyzed with 14 mm EGTA, CCCP did not provoke I(Ca) loss. Cell dialysis
      with 4 microm ruthenium red or cell superfusion with oligomycin (3 microm) plus
      rotenone (4 microm) also accelerated the decay of I(Ca). After treatment with
      CCCP, decay of N- and P/Q-type Ca(2+) channel currents occurred faster than that
      of L-type Ca(2+) channel currents. These data are compatible with the idea that
      the elevation of the bulk cytosolic Ca(2+) concentration, [Ca(2+)](c), causes the
      inhibition of L- and N- as well as P/Q-type Ca(2+) channels expressed by bovine
      chromaffin cells. This [Ca(2+)](c) signal appears to be tightly regulated by
      rapid Ca(2+) uptake into mitochondria. Thus, it is plausible that mitochondria
      might efficiently regulate the activity of L, N, and P/Q Ca(2+) channels under
      physiological stimulation conditions of the cell.

PMID- 11306609
TI  - Stimulation of beta-amyloid precursor protein trafficking by insulin reduces
      intraneuronal beta-amyloid and requires mitogen-activated protein kinase
      signaling.
AB  - Alzheimer's Disease (AD) is characterized by cerebral accumulation of beta
      amyloid peptides (Abeta), which are proteolytically derived from beta-amyloid
      precursor protein (betaAPP). betaAPP metabolism is highly regulated via various
      signal transduction systems, e.g., several serine/threonine kinases and
      phosphatases. Several growth factors known to act via receptor tyrosine kinases
      also have been demonstrated to regulate sbetaAPP secretion. Among these
      receptors, insulin and insulin-like growth factor-1 receptors are highly
      expressed in brain, especially in hippocampus and cortex. Emerging evidence
      indicates that insulin has important functions in brain regions involved in
      learning and memory. Here we present evidence that insulin significantly reduces
      intracellular accumulation of Abeta and that it does so by accelerating
      betaAPP/Abeta trafficking from the trans-Golgi network, a major cellular site for
      Abeta generation, to the plasma membrane. Furthermore, insulin increases the
      extracellular level of Abeta both by promoting its secretion and by inhibiting
      its degradation via insulin-degrading enzyme. The action of insulin on betaAPP
      metabolism is mediated via a receptor tyrosine kinase/mitogen-activated protein
      (MAP) kinase kinase pathway. The results suggest cell biological and signal
      transduction mechanisms by which insulin modulates betaAPP and Abeta trafficking
      in neuronal cultures.

PMID- 11306610
TI  - Physiological patterns of electrical stimulation can induce neuronal gene
      expression by activating N-type calcium channels.
AB  - Activity-dependent neuronal gene expression is thought to require activation of L
      type calcium channels, a view based primarily on studies in which chronic
      potassium (K(+)) depolarization was used to mimic neuronal activity. However, N
      type calcium channels are primarily inactivated during chronic depolarization,
      and their potential contribution to gene expression induced by physiological
      patterns of stimulation has not been defined. In the present study, electrical
      stimulation of dissociated primary sensory neurons at 5 Hz, or treatment with
      elevated K(+), produced a large increase in the percentage of neurons that
      express tyrosine hydroxylase (TH) mRNA and protein. However, blockade of L-type
      channels, which completely inhibited K(+)-induced expression, had no effect on TH
      expression induced by patterned stimulation. Conversely, blockade of N-type
      channels completely inhibited TH induction by patterned stimulation, whereas K(+)
      induced expression was unaffected. Similar results were obtained for
      depolarization-induced expression of the immediate early genes Nurr1 and Nur77.
      In addition, TH induction by patterned stimulation was significantly reduced by
      inhibitors of PKA and PKC but was unaffected by inhibition of the mitogen
      activated protein kinase (MAPK) pathway. On the other hand, K(+)-induced TH
      expression was significantly reduced by inhibition of the MAPK pathway but was
      unaffected by inhibitors of PKA or PKC. These results demonstrate that N-type
      calcium channels can directly link phasic membrane depolarization to gene
      expression, challenging the view that activation of L-type channels is required
      for nuclear responses to physiological patterns of activity. Moreover, our data
      show that phasic and chronic depolarizing stimuli act through distinct mechanisms
      to induce neuronal gene expression.

PMID- 11306611
TI  - Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity
      by inhibiting activation and proliferation of microglia.
AB  - Minocycline, a semisynthetic tetracycline derivative, protects brain against
      global and focal ischemia in rodents. We examined whether minocycline reduces
      excitotoxicity in primary neuronal cultures. Minocycline (0.02 microm)
      significantly increased neuronal survival in mixed spinal cord (SC) cultures
      treated with 500 microm glutamate or 100 microm kainate for 24 hr. Treatment with
      these excitotoxins induced a dose-dependent proliferation of microglia that was
      associated with increased release of interleukin-1beta (IL-1beta) and was
      followed by increased lactate dehydrogenase (LDH) release. The excitotoxicity was
      enhanced when microglial cells were cultured on top of SC cultures. Minocycline
      prevented excitotoxin-induced microglial proliferation and the increased release
      of nitric oxide (NO) metabolites and IL-1beta. Excitotoxins induced microglial
      proliferation and increased the release of NO metabolites and IL-1beta also in
      pure microglia cultures, and these responses were inhibited by minocycline. In
      both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated
      protein kinase (p38 MAPK) exclusively in microglia. Minocycline inhibited p38
      MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK
      inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal
      survival. In pure microglia cultures, glutamate induced transient activation of
      p38 MAPK, and this was inhibited by minocycline. These findings indicate that the
      proliferation and activation of microglia contributes to excitotoxicity, which is
      inhibited by minocycline, an antibiotic used in severe human infections.

PMID- 11306612
TI  - The surface accessibility of the glycine receptor M2-M3 loop is increased in the
      channel open state.
AB  - Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1
      subunit have been shown previously to affect channel gating. In this study, the
      substituted cysteine accessibility method was used to investigate whether a
      structural rearrangement of the M2-M3 loop accompanies GlyR activation. All
      residues from R271C to V277C were covalently modified by both positively charged
      methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged
      methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an
      irregular surface loop. The MTSET modification rate of all residues from R271C to
      K276C was faster in the glycine-bound state than in the unliganded state. MTSES
      modification of A272C, L274C, and V277C was also faster in the glycine-bound
      state. These results demonstrate that the surface accessibility of the M2-M3 loop
      is increased as the channel transitions from the closed to the open state,
      implying that either the loop itself or an overlying domain moves during channel
      activation.

PMID- 11306614
TI  - The homeostatic regulation of sleep need is under genetic control.
AB  - Delta power, a measure of EEG activity in the 1-4 Hz range, in slow-wave sleep
      (SWS) is in a quantitative and predictive relationship with prior wakefulness.
      Thus, sleep loss evokes a proportional increase in delta power, and excess sleep
      a decrease. Therefore, delta power is thought to reflect SWS need and its
      underlying homeostatically regulated recovery process. The neurophysiological
      substrate of this process is unknown and forward genetics might help elucidate
      the nature of what is depleted during wakefulness and recovered during SWS. We
      applied a mathematical method that quantifies the relationship between the sleep
      wake distribution and delta power to sleep data of six inbred mouse strains. The
      results demonstrated that the rate at which SWS need accumulated varied greatly
      with genotype. This conclusion was confirmed in a "dose-response" study of sleep
      loss and changes in delta power; delta power strongly depended on both the
      duration of prior wakefulness and genotype. We followed the segregation of the
      rebound of delta power after sleep deprivation in 25 BXD recombinant inbred
      strains by quantitative trait loci (QTL) analysis. One "significant" QTL was
      identified on chromosome 13 that accounted for 49% of the genetic variance in
      this trait. Interestingly, the rate at which SWS need decreases did not vary with
      genotype in any of the 31 inbred strains studied. These results demonstrate, for
      the first time, that the increase of SWS need is under a strong genetic control,
      and they provide a basis for identifying genes underlying SWS homeostasis.

PMID- 11306613
TI  - Differential mechanisms of neuroprotection by 17 beta-estradiol in apoptotic
      versus necrotic neurodegeneration.
AB  - The major goal of this study was to compare mechanisms of the neuroprotective
      potential of 17 beta-estradiol in two models for oxidative stress-independent
      apoptotic neuronal cell death with that in necrotic neuronal cell death in
      primary neuronal cultures derived from rat hippocampus, septum, or cortex.
      Neuronal apoptosis was induced either by staurosporine or ethylcholine
      aziridinium (AF64A), as models for necrotic cell death glutamate exposure or
      oxygen-glucose deprivation (OGD) were applied. Long-term (20 hr) pretreatment
      (0.1 microm 17 beta-estradiol) was neuroprotective in apoptotic neuronal cell
      death induced by AF64A (40 microm) only in hippocampal and septal neuronal
      cultures and not in cortical cultures. The neuroprotective effect was blocked by
      the estrogen antagonists ICI 182,780 and tamoxifen and the phosphatidylinositol 3
      kinase (PI3-K) inhibitor LY294002. In glutamate and OGD-induced neuronal damage,
      long-term pretreatment was not effective. In contrast, short-term (1 hr)
      pretreatment with 17 beta-estradiol in the dose range of 0.5-1.0 microm
      significantly reduced the release of lactate dehydrogenase and improved
      morphology of cortical cultures exposed to glutamate or OGD but was not effective
      in the AF64A model. Staurosporine-induced apoptosis was not prevented by either
      long- or short-term pretreatment. The strong expression of the estrogen receptor
      alpha and the modulation of Bcl proteins by 17 beta-estradiol in hippocampal and
      septal but not in cortical cultures indicates that the prevention of apoptotic,
      but not of necrotic, neuronal cell death by 17 beta-estradiol possibly depends on
      the induction of Bcl proteins and the density of estrogen receptor-alpha.

PMID- 11306615
TI  - A common mechanism underlies vertebrate calcium signaling and Drosophila
      phototransduction.
AB  - Drosophila phototransduction is an important model system for studies of inositol
      lipid signaling. Light excitation in Drosophila photoreceptors depends on
      phospholipase C, because null mutants of this enzyme do not respond to light.
      Surprisingly, genetic elimination of the apparently single inositol trisphosphate
      receptor (InsP(3)R) of Drosophila has no effect on phototransduction. This led to
      the proposal that Drosophila photoreceptors do not use the InsP(3) branch of
      phospholipase C (PLC)-mediated signaling for phototransduction, unlike most other
      inositol lipid-signaling systems. To examine this hypothesis we applied the
      membrane-permeant InsP(3)R antagonist 2-aminoethoxydiphenyl borate (2-APB), which
      has proved to be an important probe for assessing InsP(3)R involvement in various
      signaling systems. We first examined the effects of 2-APB on Xenopus oocytes. We
      found that 2-APB is efficient at reversibly blocking the robust InsP(3)-mediated
      Ca(2+) release and store-operated Ca(2+) entry in Xenopus oocytes at a stage
      operating after production of InsP(3) but before the opening of the surface
      membrane Cl(-) channels by Ca(2+). We next demonstrated that 2-APB is effective
      at reversibly blocking the response to light of Drosophila photoreceptors in a
      light-dependent manner at a concentration range similar to that effective in
      Xenopus oocytes and other cells. We show furthermore that 2-APB does not directly
      block the light-sensitive channels, indicating that it operates upstream in the
      activation of these channels. The results indicate an important link in the
      coupling mechanism of vertebrate store-operated channels and Drosophila TRP
      channels, which involves the InsP(3) branch of the inositol lipid-signaling
      pathway.

PMID- 11306616
TI  - GABA transaminase inhibition induces spontaneous and enhances depolarization
      evoked GABA efflux via reversal of the GABA transporter.
AB  - The GABA transporter can reverse with depolarization, causing nonvesicular GABA
      release. However, this is thought to occur only under pathological conditions.
      Patch-clamp recordings were made from rat hippocampal neurons in primary cell
      cultures. Inhibition of GABA transaminase with the anticonvulsant gamma-vinyl
      GABA (vigabatrin; 0.05-100 microm) resulted in a large leak current that was
      blocked by bicuculline (50 microm). This leak current occurred in the absence of
      extracellular calcium and was blocked by the GABA transporter antagonist SKF
      89976a (5 microm). These results indicate that vigabatrin induces spontaneous
      GABA efflux from neighboring cells via reversal of GABA transporters,
      subsequently leading to the stimulation of GABA(A) receptors on the recorded
      neuron. The leak current increased slowly over 4 d of treatment with 100 microm
      vigabatrin, at which time it reached an equivalent conductance of 9.0 +/- 4.9 nS.
      Blockade of glutamic acid decarboxylase with semicarbazide (2 mm) decreased the
      leak current that was induced by vigabatrin by 47%. In untreated cells, carrier
      mediated GABA efflux did not occur spontaneously but was induced by an increase
      in [K(+)](o) from 3 to as little as 6 mm. Vigabatrin enhanced this depolarization
      evoked nonvesicular GABA release and also enhanced the heteroexchange release of
      GABA induced by nipecotate. Thus, the GABA transporter normally operates near its
      equilibrium and can be easily induced to reverse by an increase in cytosolic
      [GABA] or mild depolarization. We propose that this transporter-mediated
      nonvesicular GABA release plays an important role in neuronal inhibition under
      both physiological and pathophysiological conditions and is the target of some
      anticonvulsants.

PMID- 11306617
TI  - Contribution of the plasmalemma to Ca2+ homeostasis in hair cells.
AB  - Calcium influx through transduction channels and efflux via plasmalemmal Ca(2+)
      ATPases (PMCAs) are known to contribute to calcium homeostasis and modulate
      sensory transduction in vertebrate hair cells. To examine the relative
      contributions of apical and basolateral pathways, we analyzed the calcium
      dynamics in solitary ciliated and deciliated guinea pig type I and type II
      vestibular hair cells. Whole-cell patch-clamp recordings demonstrated that these
      cells had resting potentials near -70 mV and could be depolarized by 10-20 mV by
      superfusion with high potassium. Fura-2 measurements indicated that ciliated type
      II cells and deciliated cells of either type had low basal [Ca(2+)](i), near
      approximately 90 nm, and superfusion with high potassium led to transient calcium
      increases that were diminished in the presence of Ca(2+) channel blockers. In
      contrast, measurements of type I ciliated cells, hair cells with large calyceal
      afferents, were associated with a higher basal [Ca(2+)](i) of approximately 170
      nm. High-potassium superfusion of these cells induced a paradoxical decrease in
      [Ca(2+)](i) that was augmented in the presence of Ca(2+) channel blockers.
      Optical localization of dihydropyridine binding to the kinocilium suggests that
      they contain L-type calcium channels, and as a result apical calcium influx
      includes a contribution from voltage-dependent ion channels in addition to entry
      via transduction channels localized to the stereocilia. Eosin block of PMCA
      significantly altered both [Ca(2+)](i) baseline and transient responses only in
      ciliated cells suggesting that, in agreement with immunohistochemical studies,
      PMCA is primarily localized to the bundles.

PMID- 11306618
TI  - Two-tiered inhibition of axon regeneration at the dorsal root entry zone.
AB  - Glial-derived inhibitory molecules and a weak cell-body response prevent sensory
      axon regeneration into the spinal cord after dorsal root injury. Neurotrophic
      factors, particularly neurotrophin-3 (NT-3), may increase the regenerative
      capacity of sensory neurons after dorsal rhizotomy, allowing regeneration across
      the dorsal root entry zone (DREZ). Intrathecal NT-3, delivered at the time of
      injury, promoted an upregulation of the growth-associated protein GAP-43
      primarily in large-diameter sensory profiles (which did not occur after rhizotomy
      alone), as well as regeneration of cholera toxin B-labeled sensory axons across
      the DREZ and deep into the dorsal horn. However, delaying treatment for 1 week
      compromised regeneration: although axons still penetrated the DREZ, growth within
      white matter was qualitatively and quantitatively restricted. This was not
      associated with an impaired cell-body response (GAP-43 upregulation was
      equivalent for both immediate and delayed treatments), or with astrogliosis at
      the DREZ, which begins almost immediately after rhizotomy, but with the delayed
      appearance of mature ED1-expressing phagocytes in the dorsal white matter between
      1 and 2 weeks after lesion, marking the beginning of myelin breakdown. After
      rhizotomy with immediate NT-3 treatment, regeneration continues beyond 2 weeks,
      but in the dorsal gray matter rather than in the degenerating dorsal columns. The
      ability of NT-3 to promote regeneration across the DREZ, but not after the
      beginning of degeneration after delayed treatment reveals a hierarchy of
      inhibitory influences: the astrogliotic, but not the degenerative barrier is
      surmountable by NT-3 treatment.

PMID- 11306619
TI  - DNA replication precedes neuronal cell death in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a devastating dementia of late life that is
      correlated with a region-specific neuronal cell loss. Despite progress in
      uncovering many of the factors that contribute to the etiology of the disease,
      the cause of the nerve cell death remains unknown. One promising theory is that
      the neurons degenerate because they reenter a lethal cell cycle. This theory
      receives support from immunocytochemical evidence for the reexpression of several
      cell cycle-related proteins. Direct proof for DNA replication, however, has been
      lacking. We report here the use of fluorescent in situ hybridization to examine
      the chromosomal complement of interphase neuronal nuclei in the adult human
      brain. We demonstrate that a significant fraction of the hippocampal pyramidal
      and basal forebrain neurons in AD have fully or partially replicated four
      separate genetic loci on three different chromosomes. Cells in unaffected regions
      of the AD brain or in the hippocampus of nondemented age-matched controls show no
      such anomalies. We conclude that the AD neurons complete a nearly full S phase,
      but because mitosis is not initiated, the cells remain tetraploid. Quantitative
      analysis indicates that the genetic imbalance persists for many months before the
      cells die, and we propose that this imbalance is the direct cause of the neuronal
      loss in Alzheimer's disease.

PMID- 11306620
TI  - Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in
      brain endothelial cells of rats during endotoxin-induced fever.
AB  - Fever is triggered by an elevation of prostaglandin E(2) (PGE(2)) in the brain.
      However, the mechanism of its elevation remains unanswered. We herein cloned the
      rat glutathione-dependent microsomal prostaglandin E synthase (mPGES), the
      terminal enzyme for PGE(2) biosynthesis, and examined its induction in the rat
      brain after intraperitoneal injection of pyrogen lipopolysaccharide (LPS). In
      Northern blot analysis, mPGES mRNA was weakly expressed in the brain under the
      normal conditions but was markedly induced between 2 and 4 hr after the LPS
      injection. In situ hybridization study revealed that LPS-induced mPGES mRNA
      signals were mainly associated with brain blood vessels, especially vein or
      venular-type ones, in the whole brain area. Immunohistochemical study
      demonstrated that mPGES-like immunoreactivity was expressed in the perinuclear
      region of brain endothelial cells, which were identified as von Willebrand factor
      positive cells. Furthermore, in the perinuclear region of the endothelial cells,
      mPGES was colocalized with cyclooxygenase-2 (COX-2), which is the enzyme
      essential for the production of the mPGES substrate PGH(2). Inhibition of
      cyclooxygenase-2 activity resulted in suppression of both PGE(2) level in the CSF
      and fever (Cao et al., 1997), suggesting that the two enzymes were functionally
      linked and that this link is essential for fever. These results demonstrate that
      brain endothelial cells play an essential role in the PGE(2) production during
      fever by expressing COX-2 and mPGES.

PMID- 11306621
TI  - Transport and localization of the DEG/ENaC ion channel BNaC1alpha to peripheral
      mechanosensory terminals of dorsal root ganglia neurons.
AB  - Mammalian brain sodium channel (BNaC, also known as BNC/ASIC) proteins form acid
      sensitive and amiloride-blockable sodium channels that are related to putative
      mechanosensory channels. Certain BNaC isoforms are expressed exclusively in
      dorsal root ganglia (DRG) and have been proposed to form the ion channels
      mediating tissue acidosis-induced pain. With antibody labeling, we find that the
      BNaC1alpha isoform is expressed by most large DRG neurons (low-threshold
      mechanosensors not involved in acid-induced nociception) and few small nociceptor
      neurons (which include high-threshold mechanoreceptors). BNaC1alpha is
      transported from DRG cell bodies to sensory terminals in the periphery, but not
      to the spinal cord, and is located specifically at specialized cutaneous
      mechanosensory terminals, including Meissner, Merkel, penicillate, reticular,
      lanceolate, and hair follicle palisades as well as some intraepidermal and free
      myelinated nerve endings. Accordingly, BNaC1alpha channels might participate in
      the transduction of touch and painful mechanical stimuli.

PMID- 11306622
TI  - Rapid signaling at inhibitory synapses in a dentate gyrus interneuron network.
AB  - Mutual synaptic interactions between GABAergic interneurons are thought to be of
      critical importance for the generation of network oscillations and for temporal
      encoding of information in the hippocampus. However, the functional properties of
      synaptic transmission between hippocampal interneurons are largely unknown. We
      have made paired recordings from basket cells (BCs) in the dentate gyrus of rat
      hippocampal slices, followed by correlated light and electron microscopical
      analysis. Unitary GABA(A) receptor-mediated IPSCs at BC-BC synapses recorded at
      the soma showed a fast rise and decay, with a mean decay time constant of 2.5 +/-
      0.2 msec (32 degrees C). Synaptic transmission at BC-BC synapses showed paired
      pulse depression (PPD) (32 +/- 5% for 10 msec interpulse intervals) and multiple
      pulse depression during repetitive stimulation. Detailed passive cable model
      simulations based on somatodendritic morphology and localization of synaptic
      contacts further indicated that the conductance change at the postsynaptic site
      was even faster, decaying with a mean time constant of 1.8 +/- 0.6 msec.
      Sequential triple recordings revealed that the decay time course of IPSCs at BC
      BC synapses was approximately twofold faster than that at BC-granule cell
      synapses, whereas the extent of PPD was comparable. To examine the consequences
      of the fast postsynaptic conductance change for the generation of oscillatory
      activity, we developed a computational model of an interneuron network. The model
      showed robust oscillations at frequencies >60 Hz if the excitatory drive was
      sufficiently large. Thus the fast conductance change at interneuron-interneuron
      synapses may promote the generation of high-frequency oscillations observed in
      the dentate gyrus in vivo.

PMID- 11306623
TI  - Diverse types of interneurons generate thalamus-evoked feedforward inhibition in
      the mouse barrel cortex.
AB  - Sensory information, relayed through the thalamus, arrives in the neocortex as
      excitatory input, but rapidly induces strong disynaptic inhibition that
      constrains the cortical flow of excitation both spatially and temporally. This
      feedforward inhibition is generated by intracortical interneurons whose precise
      identity and properties were not known. To characterize interneurons generating
      feedforward inhibition, neurons in layers IV and V of mouse somatosensory
      ("barrel") cortex in vitro were tested in the cell-attached configuration for
      thalamocortically induced firing and in the whole-cell mode for synaptic
      responses. Identification as inhibitory or excitatory neurons was based on
      intrinsic firing patterns and on morphology revealed by intracellular staining.
      Thalamocortical stimulation evoked action potentials in approximately 60% of
      inhibitory interneurons but in <5% of excitatory neurons. The inhibitory
      interneurons that fired received fivefold larger thalamocortical inputs compared
      with nonfiring inhibitory or excitatory neurons. Thalamocortically evoked spikes
      in inhibitory interneurons followed at short latency the onset of excitatory
      monosynaptic responses in the same cells and slightly preceded the onset of
      inhibitory responses in nearby neurons, indicating their involvement in
      disynaptic inhibition. Both nonadapting (fast-spiking) and adapting (regular
      spiking) inhibitory interneurons fired on thalamocortical stimulation, as did
      interneurons expressing parvalbumin, calbindin, or neither calcium-binding
      protein. Morphological analysis revealed that some interneurons might generate
      feedforward inhibition within their own layer IV barrel, whereas others may
      convey inhibition to upper layers, within their own or in adjacent columns. We
      conclude that feedforward inhibition is generated by diverse classes of
      interneurons, possibly serving different roles in the processing of incoming
      sensory information.

PMID- 11306624
TI  - Combinatorial expression patterns of LIM-homeodomain and other regulatory genes
      parcellate developing thalamus.
AB  - The anatomical and functional organization of dorsal thalamus (dTh) and ventral
      thalamus (vTh), two major regions of the diencephalon, is characterized by their
      parcellation into distinct cell groups, or nuclei, that can be histologically
      defined in postnatal animals. However, because of the complexity of dTh and vTh
      and difficulties in histologically defining nuclei at early developmental stages,
      our understanding of the mechanisms that control the parcellation of dTh and vTh
      and the differentiation of nuclei is limited. We have defined a set of regulatory
      genes, which include five LIM-homeodomain transcription factors (Isl1, Lhx1,
      Lhx2, Lhx5, and Lhx9) and three other genes (Gbx2, Ngn2, and Pax6), that are
      differentially expressed in dTh and vTh of early postnatal mice in distinct but
      overlapping patterns that mark nuclei or subsets of nuclei. These genes exhibit
      differential expression patterns in dTh and vTh as early as embryonic day 10.5,
      when neurogenesis begins; the expression of most of them is detected as
      progenitor cells exit the cell cycle. Soon thereafter, their expression patterns
      are very similar to those that we observe postnatally, indicating that unique
      combinations of these genes mark specific cell groups from the time they are
      generated to their later differentiation into nuclei. Our findings suggest that
      these genes act in a combinatorial manner to control the specification of nuclei
      specific properties of thalamic cells and the differentiation of nuclei within
      dTh and vTh. These genes may also influence the pathfinding and targeting of
      thalamocortical axons through both cell-autonomous and non-autonomous mechanisms.

PMID- 11306625
TI  - Ephrin B1 is expressed on neuroepithelial cells in correlation with neocortical
      neurogenesis.
AB  - To identify molecules involved in neurogenesis, we have raised monoclonal
      antibodies against embryonic day 12.5 mouse telencephalon. One antibody,
      monoclonal antibody 25H11, stains predominantly the ventricular zone of the
      anterior and lateral telencephalon. Purification of the 25H11 antigen, a 47 kDa
      integral membrane protein, from approximately 2500 mouse telencephali reveals its
      identity with ephrin B1. Ephrin B1 appears at the onset of neocortical
      neurogenesis, being first expressed in neuron-generating neuroepithelial cells
      and rapidly thereafter in virtually all neuroepithelial cells. Expression of
      ephrin B1 persists through the period of neocortical neurogenesis and is
      downregulated thereafter. Ephrin B1 is present on the ventricular as well as
      basolateral plasma membrane of neuroepithelial cells and exhibits an ventricular
      high to pial-low gradient across the ventricular zone. Expression of ephrin B1 is
      also detected on radial glial cells, extending all the way to their pial endfeet,
      and on neurons in the mantle/intermediate zone but not in the cortical plate. Our
      results suggest that ephrin B1, presumably via ephrin-Eph receptor signaling, has
      a role in neurogenesis. Given the ventricular-to-pial gradient of ephrin B1 on
      the neuroepithelial cell surface and its known role in cell migration in other
      systems mediated by its repulsive properties, we propose that ephrin B1 may be
      involved in the migration of newborn neurons out from the ventricular zone toward
      the neocortex.

PMID- 11306626
TI  - Spatiotemporal dynamics of brain-derived neurotrophic factor mRNA induction in
      the vestibulo-olivary network during vestibular compensation.
AB  - Vestibular compensation, which is the behavioral recovery from vestibular
      dysfunction produced by unilateral labyrinthectomy (UL), is attributed to
      functional and structural reorganization of neural networks in the central
      vestibular system. To assess the possible contribution of brain-derived
      neurotrophic factor (BDNF) to this recovery process, we investigated changes in
      mRNA expression levels in the central vestibular system after UL. We evaluated
      BDNF mRNA expression levels by quantitative reverse transcription-PCR and in situ
      hybridization. We found that BDNF mRNA is differentially induced in the medial
      vestibular nucleus ipsilateral to UL and in the prepositus hypoglossi and
      inferior olive on the contralateral side. The BDNF mRNA induction lasted for at
      least 24 hr and returned to the basal expression level within 72 hr after UL. In
      contrast to BDNF mRNA induction, the expression of an immediate-early gene, c
      fos, quickly reached the maximum level at 3 hr and decreased to the basal level
      within 24 hr after UL. Neither BDNF or c-fos induction was observed in sham
      operated animals. The persistent induction of BDNF after UL temporally
      corresponded to early behavioral manifestations of vestibular compensation. We
      further found that trkB mRNA was expressed in the central vestibular network at
      high levels, although its expression levels did not change over time after UL.
      Because BDNF is implicated in regulating synaptic structure and function, these
      results provide support for the hypothesis that BDNF is involved in neuronal
      reorganization that allows vestibular compensation.

PMID- 11306627
TI  - Cortical axon guidance by the glial wedge during the development of the corpus
      callosum.
AB  - Growing axons are often guided to their final destination by intermediate
      targets. In the developing spinal cord and optic nerve, specialized cells at the
      embryonic midline act as intermediate targets for guiding commissural axons. Here
      we investigate whether similar intermediate targets may play a role in guiding
      cortical axons in the developing brain. During the development of the corpus
      callosum, cortical axons from one cerebral hemisphere cross the midline to reach
      their targets in the opposite cortical hemisphere. We have identified two early
      differentiating populations of midline glial cells that may act as intermediate
      guideposts for callosal axons. The first differentiates directly below the corpus
      callosum forming a wedge shaped structure (the glial wedge) and the second
      differentiates directly above the corpus callosum within the indusium griseum.
      Axons of the corpus callosum avoid both of these populations in vivo. This
      finding is recapitulated in vitro in three-dimensional collagen gels. In
      addition, experimental manipulations in organotypic slices show that callosal
      axons require the presence and correct orientation of these populations to turn
      toward the midline. We have also identified one possible candidate for this
      activity because both glial populations express the chemorepellent molecule slit
      2, and cortical axons express the slit-2 receptors robo-1 and robo-2.
      Furthermore, slit-2 repels-suppresses cortical axon growth in three-dimensional
      collagen gel cocultures.

PMID- 11306628
TI  - Patterns of neural circuit activation and behavior during dominance hierarchy
      formation in freely behaving crayfish.
AB  - Creation of a dominance hierarchy within a population of animals typically
      involves a period of agonistic activity in which winning and losing decide
      relative positions in the hierarchy. Among crayfish, fighting between size
      matched animals leads to an abrupt change of behavior as the new subordinate
      retreats and escapes from the attacks and approaches of the dominant (Issa et
      al., 1999). We used high-speed videography and electrical recordings of aquarium
      field potentials to monitor the release of aggressive and defensive behavior,
      including the activation of neural circuits for four different tail-flip
      behaviors. We found that the sequence of tail-flip circuit excitation traced the
      development of their dominance hierarchy. Offensive tail flipping, attacks, and
      approaches by both animals were followed by a sharp rise in the frequency of
      nongiant and medial giant escape tail flips and a fall in the frequency of
      offensive tail flips of the new subordinate. These changes suggest that sudden,
      coordinated changes in the excitability of a set of neural circuits in one animal
      produce the changes in behavior that mark its transition to subordinate status.

PMID- 11306629
TI  - Spatial structure of cone inputs to color cells in alert macaque primary visual
      cortex (V-1).
AB  - The spatial structure of color cell receptive fields is controversial. Here,
      spots of light that selectively modulate one class of cones (L, M, or S, or
      loosely red, green, or blue) were flashed in and around the receptive fields of V
      1 color cells to map the spatial structure of the cone inputs. The maps generated
      using these cone-isolating stimuli and an eye-position-corrected reverse
      correlation technique produced four findings. First, the receptive fields were
      Double-Opponent, an organization of spatial and chromatic opponency critical for
      color constancy and color contrast. Optimally stimulating both center and
      surround subregions with adjacent red and green spots excited the cells more than
      stimulating a single subregion. Second, red-green cells responded in a luminance
      invariant way. For example, red-on-center cells were excited equally by a
      stimulus that increased L-cone activity (appearing bright red) and by a stimulus
      that decreased M-cone activity (appearing dark red). This implies that the
      opponency between L and M is balanced and argues that these cells are encoding a
      single chromatic axis. Third, most color cells responded to stimuli of all
      orientations and had circularly symmetric receptive fields. Some cells, however,
      showed a coarse orientation preference. This was reflected in the receptive
      fields as oriented Double-Opponent subregions. Fourth, red-green cells often
      responded to S-cone stimuli. Responses to M- and S-cone stimuli usually aligned,
      suggesting that these cells might be red-cyan. In summary, red-green (or red
      cyan) cells, along with blue-yellow and black-white cells, establish three
      chromatic axes that are sufficient to describe all of color space.

PMID- 11306630
TI  - Consistent features in the forelimb representation of primary motor cortex in
      rhesus macaques.
AB  - The purpose of this study was to systematically map the forelimb area of primary
      motor cortex (M1) in rhesus macaques in an effort to investigate further the
      organization of motor output to distal and proximal muscles. We used stimulus
      triggered averaging (StTAing) of electromyographic activity to map the cortical
      representation of 24 simultaneously recorded forelimb muscles. StTAs were
      obtained by applying 15 microA stimuli to M1 sites while the monkey performed a
      reach and prehension task. Motor output to body regions other than the forelimb
      (e.g., face, trunk, and hindlimb) was identified using repetitive intracortical
      microstimulation to evoke movements. Detailed, muscle-based maps of M1 revealed a
      central core of distal (wrist, digit, and intrinsic hand) muscle representation
      surrounded by a "horseshoe"-shaped zone of proximal (shoulder and elbow) muscle
      representation. The core distal and proximal zones were separated by a relatively
      large region representing combinations of both distal and proximal muscles. On
      the basis of its size and characteristics, we argue that this zone is not simply
      the result of stimulus-current spread, but rather a distinct zone within the
      forelimb representation containing cells that specify functional synergies of
      distal and proximal muscles. Electrode tracks extending medially from the medial
      arm of the proximal muscle representation evoked trunk and hindlimb responses. No
      distal or proximal muscle poststimulus effects were found in this region. These
      results argue against the existence of a second, major noncontiguous distal or
      proximal forelimb representation located medially within the macaque M1
      representation.

PMID- 11306631
TI  - Predictability modulates human brain response to reward.
AB  - Certain classes of stimuli, such as food and drugs, are highly effective in
      activating reward regions. We show in humans that activity in these regions can
      be modulated by the predictability of the sequenced delivery of two mildly
      pleasurable stimuli, orally delivered fruit juice and water. Using functional
      magnetic resonance imaging, the activity for rewarding stimuli in both the
      nucleus accumbens and medial orbitofrontal cortex was greatest when the stimuli
      were unpredictable. Moreover, the subjects' stated preference for either juice or
      water was not directly correlated with activity in reward regions but instead was
      correlated with activity in sensorimotor cortex. For pleasurable stimuli, these
      findings suggest that predictability modulates the response of human reward
      regions, and subjective preference can be dissociated from this response.

PMID- 11306632
TI  - Progression of changes in dopamine transporter binding site density as a result
      of cocaine self-administration in rhesus monkeys.
AB  - The present study examined the time course of alterations in levels of dopamine
      transporter (DAT) binding sites that accompany cocaine self-administration using
      quantitative in vitro receptor autoradiography with [(3)H]WIN 35,428. The density
      of dopamine transporter binding sites in the striatum of rhesus monkeys with 5 d,
      3.3 months, or 1.5 years of cocaine self-administration experience was compared
      with DAT levels in cocaine-naive control monkeys. Animals in the long-term (1.5
      years) exposure group self-administered cocaine at 0.03 mg/kg per injection,
      whereas the initial (5 d) and chronic (3.3 months) treatment groups were each
      divided into lower dose (0.03 mg/kg per injection) and higher dose (0.3 mg/kg per
      injection) groups. Initial cocaine exposure led to moderate decreases in
      [(3)H]WIN 35,428 binding sites, with significant changes in the dorsolateral
      caudate (-25%) and central putamen (-19%) at the lower dose. Longer exposure, in
      contrast, resulted in elevated levels of striatal binding sites. The increases
      were most pronounced in the ventral striatum at the level of the nucleus
      accumbens shell. At the lower dose of the chronic phase, for example, significant
      increases of 21-42% were measured at the caudal level of the ventral caudate,
      ventral putamen, olfactory tubercle, and accumbens core and shell. Systematic
      variation of cocaine dose and drug exposure time demonstrated the importance of
      these factors in determining the intensity of increased DAT levels. With self
      administration of higher doses especially, increases were more intense and
      included dorsal portions of the striatum so that every region at the caudal level
      exhibited a significant increase in DAT binding sites (20-54%). The similarity of
      these findings to previous studies in human cocaine addicts strongly suggest that
      the increased density of dopamine transporters observed in studies of human drug
      abusers are the result of the neurobiological effects of cocaine, ruling out
      confounds such as polydrug abuse, preexisting differences in DAT levels, or
      comorbid psychiatric conditions.

PMID- 11306633
TI  - Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states
      mediated by spinal cord proinflammatory cytokines.
AB  - Perispinal (intrathecal) injection of the human immunodeficiency virus-1 (HIV-1)
      envelope glycoprotein gp120 creates exaggerated pain states. Decreases in
      response thresholds to both heat stimuli (thermal hyperalgesia) and light tactile
      stimuli (mechanical allodynia) are rapidly induced after gp120 administration.
      gp120 is the portion of HIV-1 that binds to and activates microglia and
      astrocytes. These glial cells have been proposed to be key mediators of gp120
      induced hyperalgesia and allodynia because these pain changes are blocked by
      drugs thought to affect glial function preferentially. The aim of the present
      series of studies was to determine whether gp120-induced pain changes involve
      proinflammatory cytokines [interleukin-1beta (IL-1) and tumor necrosis factor
      alpha (TNF-alpha)], substances released from activated glia. IL-1 and TNF
      antagonists each prevented gp120-induced pain changes. Intrathecal gp120 produced
      time-dependent, site-specific increases in TNF and IL-1 protein release into
      lumbosacral CSF; parallel cytokine increases in lumbar dorsal spinal cord were
      also observed. Intrathecal administration of fluorocitrate (a glial metabolic
      inhibitor), TNF antagonist, and IL-1 antagonist each blocked gp120-induced
      increases in spinal IL-1 protein. These results support the concept that
      activated glia in dorsal spinal cord can create exaggerated pain states via the
      release of proinflammatory cytokines.

PMID- 11306634
TI  - Regulation of limbic information outflow by the subthalamic nucleus: excitatory
      amino acid projections to the ventral pallidum.
AB  - The subthalamic nucleus (STN), a component of the basal ganglia motor system,
      sends an excitatory amino acid (EAA)-containing projection to the ventral
      pallidum (VP), a major limbic system output region. The VP contains both NMDA and
      AMPA subtypes of EAA receptors. To characterize the physiology of the subthalamic
      pathway to the VP, and to determine the influence of EAA receptor subtypes, in
      vivo intracellular recordings, and in vivo extracellular recordings combined with
      microiontophoresis, were made from VP neurons in anesthetized rats. Of the
      intracellularly recorded neurons, 86% responded to STN stimulation, and these
      displayed EPSPs with an onset of 8.7 msec, consistent with a monosynaptic input.
      The EPSPs evoked in spontaneously firing neurons were nearly twice the amplitude
      of those in nonfiring cells (13.1 vs 6.8 mV, respectively). As neurons were
      depolarized by current injection, the latency for spiking decreased from 24.2 to
      14.2 msec, although EPSP latency was unaffected. Eighty-seven percent of the
      extracellularly recorded VP neurons responded to STN stimulation with a rapid and
      robust enhancement of spiking; the response onset, like the EPSP onset, equaled
      8.7 msec. Firing rate was enhanced by NMDA in 94% of the STN-excited cells, and
      AMPA increased firing in 94% as well. The NMDA-selective antagonist AP-5
      attenuated 67% of the STN-evoked excitatory responses, and the AMPA-selective
      antagonist CNQX attenuated 52%. Both antagonists attenuated 33% of responses, and
      78% were attenuated by at least one. This evidence suggests that a great majority
      of VP neurons are directly influenced by STN activation and that both NMDA and
      non-NMDA receptors are involved. Moreover, the VP response to STN stimulation
      appears to be strongly dependent on the depolarization state of the neuron.

PMID- 11306635
TI  - Regulation of serotonin release in the lateral septum and striatum by
      corticotropin-releasing factor.
AB  - The serotonergic dorsal raphe nucleus (DRN) is innervated by corticotropin
      releasing factor (CRF)-immunoreactive fibers and contains CRF receptor-binding
      sites, suggesting that endogenous CRF regulates this system. The present study
      examined the possibility that CRF in the DRN regulates the release of serotonin
      (5-HT) in forebrain terminal regions. Intracerebroventricular administration of
      CRF produced a bimodal effect on extracellular levels of 5-HT in the lateral
      septum. Doses of 0.3 and 1.0 microg decreased extracellular 5-HT levels, whereas
      both a higher (3.0 microg) and a lower (0.1 microg) dose had no effect. The
      reduction of extracellular 5-HT in the lateral septum by CRF (0.3 microg, i.c.v.)
      was blocked by pretreatment with the CRF receptor antagonist d-PheCRF(12-41) (3.0
      microg, i.c.v.). Direct administration of CRF (30 ng) into the DRN reduced
      extracellular 5-HT levels in the lateral septum and the striatum. Furthermore,
      injection of d-PheCRF(12-41) (10 ng) into the DRN before ventricular
      administration of CRF (0.3 microg, i.c.v.) blocked the decrease in extracellular
      5-HT in both the lateral septum and striatum. Taken together, these data support
      the hypothesis that CRF may modulate 5-HT release in terminal regions via its
      effects at the level of the DRN. This modulation supports a potential interaction
      between CRF and 5-HT in stress-related psychiatric disorders in which both
      systems have been implicated.

PMID- 11306636
TI  - Neuronal population codes and the perception of object distance in weakly
      electric fish.
AB  - Weakly electric fish use an electric sense to navigate and capture prey in the
      dark. Objects in the surroundings of the fish produce distortions in their self
      generated electric field; these distortions form a two-dimensional Gaussian-like
      electric image on the skin surface. To determine the distance of an object, the
      peak amplitude and width of its electric image must be estimated. These sensory
      features are encoded by a neuronal population in the early stages of the
      electrosensory pathway, but are not represented with classic bell-shaped neuronal
      tuning curves. In contrast, bell-shaped tuning curves do characterize the
      neuronal responses to the location of the electric image on the body surface,
      such that parallel two-dimensional maps of this feature are formed. In the case
      of such two-dimensional maps, theoretical results suggest that the width of
      neural tuning should have no effect on the accuracy of a population code. Here we
      show that although the spatial scale of the electrosensory maps does not affect
      the accuracy of encoding the body surface location of the electric image, maps
      with narrower tuning are better for estimating image width and those with wider
      tuning are better for estimating image amplitude. We quantitatively evaluate a
      two-step algorithm for distance perception involving the sequential estimation of
      peak amplitude and width of the electric image. This algorithm is best
      implemented by two neural maps with different tuning widths. These results
      suggest that multiple maps of sensory features may be specialized with different
      tuning widths, for encoding additional sensory features that are not explicitly
      mapped.

PMID- 11306637
TI  - Modulation of hippocampal and amygdalar-evoked activity of nucleus accumbens
      neurons by dopamine: cellular mechanisms of input selection.
AB  - Inputs from multiple sites in the telencephalon, including the hippocampus and
      basolateral amygdala (BLA), converge on neurons in the nucleus accumbens (NAc),
      and dopamine (DA) is believed to play an essential role in the amplification and
      gating of these different limbic inputs. The present study used extracellular
      single-unit recordings of NAc neurons in combination with chronoamperometric
      sampling of mesoaccumbens DA efflux to assess the importance of DA in the
      integration of different limbic inputs to the NAc. Tetanic stimulation of the
      fimbria potentiated hippocampal-evoked firing activity of NAc neurons and
      increased DA extracellular levels. Systemic administration of the D(1) receptor
      antagonist SCH23390 or the NMDA receptor antagonist CPP abolished the
      potentiation of hippocampal-evoked activity and produced a D(2) receptor-mediated
      suppression of evoked firing. In neurons that received converging input from the
      hippocampus and BLA, fimbria tetanus potentiated hippocampal-evoked firing
      activity and suppressed BLA-evoked activity in the same neurons. Both D(1) and
      NMDA receptors participated in the potentiation of fimbria-evoked activity,
      whereas the suppression of BLA-evoked activity was blocked by either D(1)
      receptor antagonism with SCH23390 or the adenosine A(1) antagonist 8-cyclopentyl
      1,2-dimethylxanthine. Coincidental tetanus of both the fimbria and BLA resulted
      in potentiation of both inputs, indicating that DA and adenosine-mediated
      suppression of BLA-evoked firing was activity-dependent. These data suggest that
      increases in mesoaccumbens DA efflux by hippocampal afferents to the NAc play a
      critical role in an input selection mechanism, which can ensure preferential
      responding to the information conveyed from the hippocampus to the ventral
      striatum.

PMID- 11306638
TI  - Distinct K currents result in physiologically distinct cell types in the inferior
      colliculus of the rat.
AB  - The inferior colliculus (IC) processes auditory information ascending from the
      brainstem. The response of the IC to this information and its ability to
      transform it is partly determined by the types of ionic currents that generate
      the intrinsic discharge patterns of IC neurons and their susceptibility to
      changes in the external environment. We have used whole-cell patch-clamp
      techniques on IC neurons in rat brain slices to characterize the potassium
      currents present and to correlate them with the firing patterns observed. Neurons
      in the IC can be classified into six physiologically distinct cell types. Each of
      these cell types has a firing pattern that is generated by a unique potassium
      current and set of cellular parameters. Sustained-regular cells show mainly
      delayed rectifier K(+) channels. Onset cells have a unique high-threshold
      tetraethylammonium-sensitive K(+) current. Pause-build cells have an A-current.
      Rebound-regular cells have calcium-dependent rebound depolarizations. Rebound
      adapting cells have both an apamin-sensitive calcium-dependent K(+) current and a
      calcium-dependent rebound depolarization. Transient-rebound cells have a
      charybdotoxin-sensitive calcium-dependent K(+) current and a calcium-dependent
      rebound. Our data suggest that there would be similarities as well as differences
      among IC neurons in their responses to excitatory or inhibitory inputs.
      Furthermore, some cells are likely to show little or no plasticity and behave as
      simple relays of temporal and intensity information, whereas others are likely to
      transform their inputs.

PMID- 11306639
TI  - Propagation of neocortical inputs in the perirhinal cortex.
AB  - The perirhinal area is a rostrocaudally oriented strip of cortex in which lesions
      produce memory and perceptual impairments. It receives topographically organized
      transverse projections from associative neocortical areas and is endowed with
      intrinsic longitudinal connections that could distribute neocortical inputs in
      the rostrocaudal axis. In search of distinguishing network properties that might
      support perirhinal involvement in memory, we have performed whole-cell recordings
      in horizontal perirhinal slices with preserved transverse neocortical links and
      intrinsic longitudinal connections. Neocortical stimulation sites in rostrocaudal
      register with regular spiking perirhinal neurons elicited a sequence of
      excitatory and inhibitory synaptic potentials. In contrast, apparently pure
      excitatory responses were observed when the stimulating and recording sites were
      separated by >/=1 mm in the rostrocaudal axis. This suggested that adjacent and
      distant neocortical stimuli influence regular spiking perirhinal neurons by
      pathways that respectively form and do not form synapses with inhibitory
      interneurons. In keeping with this, presumed interneurons did not respond to
      distant neocortical stimuli. These results suggest that neocortical inputs
      recruit perirhinal inhibitory interneurons located at the same transverse level,
      limiting the depolarization of principal perirhinal cells. In contrast, distant
      neocortical inputs only evoke excitation because longitudinal perirhinal pathways
      do not engage inhibitory interneurons. This leads us to suggest that the
      perirhinal network is biased to favor Hebbian-like associative interactions
      between coincident and spatially distributed inputs.

PMID- 11306640
TI  - Growth and functional efficacy of intrastriatal nigral transplants depend on the
      extent of nigrostriatal degeneration.
AB  - Previous studies have shown that the functional efficacy of intrastriatal
      transplants of fetal dopamine (DA) neurons in the rat Parkinson model depends on
      their ability to establish a new functional innervation of the denervated
      striatum. Here we report that the survival, growth, and function of the grafted
      DA neurons greatly depend on the severity of the lesion of the host nigrostriatal
      system. Fiber outgrowth, and to a lesser extent also cell survival, were
      significantly reduced in animals in which part of the intrinsic DA system was
      left intact. Moreover, graft-induced functional recovery, as assessed in the
      stepping, paw-use, and apomorphine rotation tests, was obtained only in severely
      lesioned animals, i.e., in rats with >70% DA denervation of the host striatum.
      Functional recovery seen in these animals in which the 6-hydroxydopamine (6-OHDA)
      lesion was confined to the striatum was more pronounced than that previously
      obtained in rats with complete lesions of the mesencephalic DA system, indicating
      that spared portions of the host DA system, particularly those innervating
      nonstriatal forebrain areas, may be necessary for the grafts to exert their
      optimal functional effect. These data have implications for the optimal use of
      fetal nigral transplants in Parkinson patients in different stages of the
      disease.

PMID- 11306641
TI  - Circadian clock regulation of pH in the rabbit retina.
AB  - Although it is generally accepted that the acid-base ratio of tissue, as
      represented by the pH, is strictly regulated to maintain normal function, recent
      studies in the mammalian nervous system have shown that neuronal activity can
      result in significant shifts in pH. In the mammalian retina, many cellular
      phenomena, including neuronal activity, are regulated by a circadian clock. We
      thus investigated whether a clock regulates retinal pH, using pH-sensitive
      microelectrodes to measure the extracellular pH (pH(o)) of the in vitro rabbit
      retina in the subjective day and night, that is, under conditions of constant
      darkness. These measurements demonstrated that a circadian clock regulates the
      pH(o) of the rabbit retina so that the pH(o) is lower at night than in the day.
      This day/night difference in retinal pH(o) was observed when the rabbits were
      maintained on a normal light/dark cycle and after they were maintained on a
      light/dark cycle that was phase-delayed by 9 hr. Continuous recordings of retinal
      pH(o) around subjective dusk indicated that the change from daytime to nighttime
      pH(o) is relatively fast and suggested that the clock that regulates pH(o) is
      located in the retina. The lowest pH(o) recorded in the retina in both the day
      and night was in the vicinity of the inner segments of photoreceptor cells,
      supporting the idea that photoreceptors serve as the primary source of protons.
      The circadian-induced shift in pH(o) was several times greater than light-induced
      pH(o) changes. These findings suggest that a circadian clock in the mammalian
      retina regulates retinal pH.

PMID- 11306642
TI  - Multiple types of control by identified interneurons in a sensory-activated
      rhythmic motor pattern.
AB  - Modulatory interneurons that can drive central pattern generators (CPGs) are
      considered as good candidates for decision-making roles in rhythmic behaviors.
      Although the mechanisms by which such neurons activate their target CPGs are
      known in detail in many systems, their role in the sensory activation of CPG
      driven behaviors is poorly understood. In the feeding system of the mollusc
      Lymnaea, one of the best-studied rhythmical networks, intracellular stimulation
      of either of two types of neuron, the cerebral ventral 1a (CV1a) and the slow
      oscillator (SO) cells, leads to robust CPG-driven fictive feeding patterns,
      suggesting that they might make an important contribution to natural food
      activated behavior. In this paper we investigated this contribution using a lip
      CNS preparation in which feeding was elicited with a natural chemostimulant
      rather than intracellular stimulation. We found that despite their CPG-driving
      capabilities, neither CV1a nor SO were involved in the initial activation of
      sucrose-evoked fictive feeding, whereas a CPG interneuron, N1M, was active first
      in almost all preparations. Instead, the two interneurons play important and
      distinct roles in determining the characteristics of the rhythmic motor output;
      CV1a by modulating motoneuron burst duration and SO by setting the frequency of
      the ongoing rhythm. This is an example of a distributed system in which (1)
      interneurons that drive similar motor patterns when activated artificially
      contribute differently to the shaping of the motor output when it is evoked by
      the relevant sensory input, and (2) a CPG rather than a modulatory interneuron
      type plays the most critical role in initiation of sensory-evoked rhythmic
      activity.

PMID- 11306643
TI  - Deficiency of growth hormone-releasing hormone signaling is associated with sleep
      alterations in the dwarf rat.
AB  - The somatotropic axis, and particularly growth hormone-releasing hormone (GHRH),
      is implicated in the regulation of sleep-wake activity. To evaluate sleep in
      chronic somatotropic deficiency, sleep-wake activity was studied in dwarf (dw/dw)
      rats that are known to have a defective GHRH signaling mechanism in the pituitary
      and in normal Lewis rats, the parental strain of the dw/dw rats. In addition,
      expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and
      in the pituitary was also determined by means of reverse transcription-PCR, and
      GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and
      pituitary GHRH-R mRNA levels were decreased in the dw/dw rats, indicating
      deficits in the central GHRHergic transmission. Hypothalamic GHRH content in
      dw/dw rats was also less than that found in Lewis rats. The dw/dw rats had less
      spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid
      eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4
      hr of sleep deprivation, rebound increases in NREMS and REMS were normal in the
      dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram
      (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in
      the dw/dw rats were only one-half of the response in the Lewis rats. The results
      are compared with sleep findings previously obtained in GHRH-deficient transgenic
      mice. The alterations in NREMS are attributed to the defect in GHRH signaling,
      whereas the decreases in REMS might result from the growth hormone deficiency in
      the dw/dw rat.

PMID- 11306644
TI  - Functional anatomy of nonvisual feedback loops during reaching: a positron
      emission tomography study.
AB  - Reaching movements performed without vision of the moving limb are continuously
      monitored, during their execution, by feedback loops (designated nonvisual). In
      this study, we investigated the functional anatomy of these nonvisual loops using
      positron emission tomography (PET). Seven subjects had to "look at" (eye) or
      "look and point to" (eye-arm) visual targets whose location either remained
      stationary or changed undetectably during the ocular saccade (when vision is
      suppressed). Slightly changing the target location during gaze shift causes an
      increase in the amount of correction to be generated. Functional anatomy of
      nonvisual feedback loops was identified by comparing the reaching condition
      involving large corrections (jump) with the reaching condition involving small
      corrections (stationary), after subtracting the activations associated with
      saccadic movements and hand movement planning [(eye-arm-jumping minus eye
      jumping) minus (eye-arm-stationary minus eye-stationary)]. Behavioral data
      confirmed that the subjects were both accurate at reaching to the stationary
      targets and able to update their movement smoothly and early in response to the
      target jump. PET difference images showed that these corrections were mediated by
      a restricted network involving the left posterior parietal cortex, the right
      anterior intermediate cerebellum, and the left primary motor cortex. These
      results are consistent with our knowledge of the functional properties of these
      areas and more generally with models emphasizing parietal-cerebellar circuits for
      processing a dynamic motor error signal.

PMID- 11306645
TI  - Neural processing of naturalistic optic flow.
AB  - Stimuli traditionally used for analyzing visual information processing are much
      simpler than what an animal sees in normal life. When characterized with
      traditional stimuli, neuronal responses were found to depend on various
      parameters such as contrast, texture, or velocity of motion, and thus were highly
      ambiguous. In behavioral situations, all of these parameters change
      simultaneously and differently in different parts of the visual field. Thus it is
      hardly possible to predict from traditional analyses what information is encoded
      by neurons in behavioral situations. Therefore, we characterized an identified
      neuron in the optomotor system of the blowfly with image sequences as they were
      seen by animals walking in a structured environment. We conclude that during
      walking, the response of the neuron reflects the animal's turning direction
      nearly independently of the texture and spatial layout of the environment. Our
      findings stress the significance of analyzing the performance of neuronal
      circuits under their natural operating conditions.

PMID- 11306646
TI  - Early onset of spontaneous activity in uninjured C-fiber nociceptors after injury
      to neighboring nerve fibers.
AB  - Ligation and transection of the L5 spinal nerve in the rat lead to behavioral
      signs of pain and hyperalgesia. Discharge of injured nociceptors has been
      presumed to play a role in generating the pain. However, A fibers, but not C
      fibers, in the injured L5 spinal nerve have been shown to develop spontaneous
      activity. Moreover, an L5 dorsal root rhizotomy does not reverse this pain
      behavior, suggesting that signals from other uninjured spinal nerves are
      involved. We asked if abnormal activity develops in an adjacent, uninjured root.
      Single nerve fiber recordings were made from the L4 spinal nerve after ligation
      and transection of the L5 spinal nerve. Within 1 d of the lesion, spontaneous
      activity developed in approximately half of the C fiber afferents. This
      spontaneous activity was at a low level (median rate, seven action potentials/5
      min), originated distal to the dorsal root ganglion, and was present in
      nociceptive fibers with cutaneous receptive fields. The incidence and level of
      spontaneous activity were similar 1 week after injury. The early onset of
      spontaneous activity in uninjured nociceptive afferents could be the signal that
      produces the central sensitization responsible for the development of mechanical
      hyperalgesia. Because L4 afferents comingle with degenerating L5 axons in the
      peripheral nerve, we hypothesize that products associated with Wallerian
      degeneration lead to an alteration in the properties of the adjacent, uninjured
      afferents.

PMID- 11306647
TI  - Absorbing competition for carnitine.

PMID- 11306648
TI  - The adenosine A(2A) receptor of the basal ganglia.

PMID- 11306649
TI  - Three Ca2+ levels affect plasticity differently: the LTP zone, the LTD zone and
      no man's land.

PMID- 11306651
TI  - Na+- and Cl--coupled active transport of carnitine by the amino acid transporter
      ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes.
AB  - 1. ATB(0,+) is an amino acid transporter energized by transmembrane gradients of
      Na+ and Cl(-) and membrane potential. We cloned this transporter from mouse colon
      and expressed the clone functionally in mammalian (human retinal pigment
      epithelial, HRPE) cells and Xenopus laevis oocytes to investigate the interaction
      of carnitine and its acyl esters with the transporter. 2. When expressed in
      mammalian cells, the cloned ATB(0,+) was able to transport carnitine,
      propionylcarnitine and acetylcarnitine. The transport process was Na(+) and Cl(-)
      dependent and inhibitable by the amino acid substrates of the transporter. The
      Michaelis constant for carnitine was 0.83 +/- 0.08 mM and the Hill coefficient
      for Na(+) activation was 1.6 +/- 0.1. 3. When expressed in Xenopus laevis
      oocytes, the cloned ATB(0,+) was able to induce inward currents in the presence
      of carnitine and propionylcarnitine under voltage-clamped conditions. There was
      no detectable current in the presence of acetylcarnitine. Carnitine-induced
      currents were obligatorily dependent on the presence of Na(+) and Cl(-). The
      currents were saturable with carnitine and the Michaelis constant was 1.8 +/- 0.4
      mM. The analysis of Na(+)- and Cl(-)-activation kinetics revealed that 2 Na(+)
      and 1 Cl(-) were involved in the transport of carnitine via the transporter. 4.
      These studies describe the identification of a novel function for the amino acid
      transporter ATB(0,+). Since this transporter is expressed in the intestinal
      tract, lung and mammary gland, it is likely to play a significant role in the
      handling of carnitine in these tissues. 5. A Na(+)-dependent transport system for
      carnitine has already been described. This transporter, known as OCTN2 (novel
      organic cation transporter 2), is expressed in most tissues and transports
      carnitine with high affinity. It is energized, however, only by a Na(+) gradient
      and membrane potential. In contrast, ATB(0,+) is a low-affinity transporter for
      carnitine, but exhibits much higher concentrative capacity than OCTN2 because of
      its energization by transmembrane gradients of Na(+) and Cl(-) as well as by
      membrane potential.

PMID- 11306650
TI  - Vesicular trafficking machinery, the actin cytoskeleton, and H+-K+-ATPase
      recycling in the gastric parietal cell.
AB  - Gastric HCl secretion by the parietal cell involves the secretagogue-regulated re
      cycling of the H+-K+-ATPase at the apical membrane. The trafficking of the H+-K+
      ATPase and the remodelling of the apical membrane during this process are likely
      to involve the co-ordination of the function of vesicular trafficking machinery
      and the cytoskeleton. This review summarizes the progress made in the
      identification and characterization of components of the vesicular trafficking
      machinery that are associated with the H+-K+-ATPase and of components of the
      actin-based cytoskeleton that are associated with the apical membrane of the
      parietal cell. Since many of these proteins are also expressed at the apical pole
      of other epithelial cells, the parietal cell may represent a model system to
      characterize the protein- protein interactions that regulate apical membrane
      trafficking in many other epithelial cells.

PMID- 11306652
TI  - A light-dependent increase in free Ca2+ concentration in the salamander rod outer
      segment.
AB  - 1. The Ca(2+) indicator dye fluo-5F was excited by an argon ion laser to measure
      changes in free Ca(2+) concentration ([Ca2+]i) in the outer segments of isolated
      salamander rods rapidly exposed to a 0 Ca(2+), 0 Na(+) solution designed to
      minimise surface membrane Ca(2+) fluxes. Over 30-60 s of laser illumination, the
      fluorescence first increased rapidly and then declined at a rate that was much
      slower than in Ringer solution and consistent with previous physiological
      evidence that 0 Ca(2+), 0 Na(+) solution greatly retards light-induced changes in
      [Ca(2+)]i. 2. The initial increase in fluorescence was investigated with a
      sequence of 100 ms laser flashes presented at 5 s intervals. The fluorescence
      evoked by the second laser flash was on average 30 % larger than the first, and
      subsequent responses exhibited a slow decline like that measured with continuous
      laser exposures. The initial increase in fluorescence did not depend upon the
      timing of exposure to 0 Ca(2+), 0 Na(+) solution but appeared to be evoked by
      exposure to the laser light. 3. Both the increase and subsequent decline in
      fluorescence measured with brief laser flashes could be reduced by incorporation
      of the Ca(2+) chelator BAPTA. This and other results indicate that the
      fluorescence increase was unlikely to have been caused by a change in the
      affinity of fluo-5F for Ca(2+) or an increase in the quantity of incorporated dye
      available to bind Ca(2+) but reflects an actual release of intracellular Ca(2+)
      within the outer segment. 4. The pool of Ca(2+) available to be released could be
      decreased if, before the first laser flash, the rod was exposed to light bright
      enough to bleach a substantial fraction of the photopigment. The releasable pool
      could also be depleted by exposure to saturating light of much lower intensity if
      delivered in Ringer solution but not if delivered in 0 Ca(2+), 0 Na(+) solution.
      We conclude that Ca(2+) can be released within the outer segment both by the
      bleaching of rhodopsin and by the reduction in [Ca(2+)]i which normally
      accompanies illumination in Ringer solution. 5. The activation of rhodopsin
      appears somehow to induce the release of Ca(2+) from a binding site or store
      within the outer segment. Substantial release, however, required stimulating
      light of an intensity sufficient to bleach a considerable fraction of the visual
      pigment. It therefore seems unlikely that such release contributes to the normal
      Ca(2+)-mediated modulation of transduction during light adaptation. The mechanism
      and physiological function of light-induced Ca(2+) release are unknown.

PMID- 11306653
TI  - Calcium influx-independent depression of transmitter release by 5-HT at lamprey
      spinal cord synapses.
AB  - 1. The mechanisms by which 5-hydroxytryptamine (5-HT) depresses transmitter
      release from lamprey reticulospinal axons were investigated. These axons make
      glutamatergic synapses onto spinal ventral horn neurons. 5-HT reduces release at
      these synapses, yet the mechanisms remain unclear. 2. Excitatory postsynaptic
      currents (EPSCs) evoked by stimulation of reticulospinal axons were recorded in
      ventral horn neurons. 5-HT depressed the EPSCs in a dose-dependent manner with an
      apparent Km of 2.3 microM. 3. To examine the presynaptic effect of 5-HT,
      electrophysiological and optical recordings were made from presynaptic axons.
      Action potentials evoked Ca(2+) transients in the axons loaded with a Ca(2+)
      sensitive dye. 5-HT slightly reduced the Ca(2+) transient. 4. A third-power
      relationship between Ca(2+) entry and transmitter release was determined.
      However, presynaptic Ca(2+) currents were unaffected by 5-HT. 5. Further, in the
      presence of a K(+) channel blocker, 4-aminopyridine (4-AP), 5-HT left unaltered
      the presynaptic Ca(2+) transient, ruling out the possibility of its direct action
      on presynaptic Ca(2+) current. 5-HT activated a 4-AP-sensitive current with a
      reversal potential of -95 mV in these axons. 6. The basal Ca(2+) concentration
      did not affect 5-HT-mediated inhibition of release. Although 5-HT caused a subtle
      reduction in resting axonal [Ca(2+)]i, synaptic responses recorded during
      enhanced resting [Ca(2+)]i, by giving stimulus trains, were equally depressed by
      5-HT. 7. 5-HT reduced the frequency of TTX-insensitive spontaneous EPSCs at these
      synapses, but had no effect on their amplitude. We propose a mechanism of
      inhibition for transmitter release by 5-HT that is independent of presynaptic
      Ca(2+) entry.

PMID- 11306654
TI  - RGS2 blocks slow muscarinic inhibition of N-type Ca(2+) channels reconstituted in
      a human cell line.
AB  - 1. Native N-type Ca(2+) channels undergo sustained inhibition through a slowly
      activating pathway linked to M1 muscarinic acetylcholine receptors and Galphaq/11
      proteins. Little is known concerning the regulation of this slow inhibitory
      pathway. We have reconstituted slow muscarinic inhibition of N-type channels in
      HEK293 cells (a human embryonic kidney cell line) by coexpressing cloned alpha1B
      (Ca(V)2.2) Ca(2+) channel subunits and M1 receptors. Expressed Ca(2+) currents
      were recorded using standard whole-cell, ruptured-patch techniques. 2. Rapid
      application of carbachol produced two kinetically distinct components of Ca(2+)
      channel inhibition. The fast component of inhibition had a time constant of < 1
      s, whereas the slow component had a time constant of 5-40 s. Neither component of
      inhibition was reduced by pertussis toxin (PTX) or staurosporine. 3. The fast
      component of inhibition was selectively blocked by the Gbetagamma-binding region
      of beta-adrenergic receptor kinase 1, suggesting that fast inhibition is mediated
      by Gbetagamma released from Galphaq/11. 4. The slow component of inhibition was
      selectively blocked by regulator of G protein signalling 2 (RGS2), which
      preferentially interacts with Galphaq/11 proteins. RGS2 also attenuated channel
      inhibition produced by intracellular dialysis with non-hydrolysable GTPgammaS.
      Together these results suggest that RGS2 selectively blocked slow inhibition by
      functioning as an effector antagonist, rather than as a GTPase-accelerating
      protein (GAP). 5. These experiments demonstrate that slow muscarinic inhibition
      of N-type Ca(2+) channels can be reconstituted in non-neuronal cells, and that
      RGS2 can selectively block slow muscarinic inhibition while leaving fast
      muscarinic inhibition intact. These results identify RGS2 as a potential
      physiological regulator of the slow muscarinic pathway.

PMID- 11306655
TI  - External K(+) relieves the block but not the gating shift caused by Zn(2+) in
      human Kv1.5 potassium channels.
AB  - 1. We used the whole-cell recording technique to examine the effect of
      extracellular Zn(2+) on macroscopic currents due to Kv1.5 channels expressed in
      the human embryonic kidney cell line HEK293. 2. Fits of a Boltzmann function to
      tail current amplitudes showed that 1 mM Zn2+ shifted the half-activation voltage
      from -10.2 +/- 0.4 to 21.1 +/- 0.7 mV and the slope factor increased from 6.8 +/-
      0.4 to 9.4 +/- 0.7 mV. The maximum conductance in 1 mM Zn2+ and with 3.5 mM K(+)o
      was 33 +/- 7 % of the control value. 3. In physiological saline the apparent KD
      for the Zn(2+) block was 650 +/- 24 M and was voltage independent. A Hill
      coefficient of 1.0 +/- 0.03 implied that block is mediated by the occupation of a
      single binding site. 4. Increasing the external concentration of K(+) ([K(+)]o)
      inhibited the block by Zn(2+). Estimates of the apparent K(D) of the Zn(2+) block
      in 0, 5 and 135 mM K(+) were 69, 650 and 2100 M, respectively. External Cs(+)
      relieved the Zn(2+) block but was less effective than K(+). Changing [K(+)]o did
      not affect the Zn(2+)-induced gating shift. 5. A model of allosteric inhibition
      fitted to the relationship between the block by Zn(2+) and the block relief by
      external K(+) gave KD estimates of approximately 70 M for Zn(2+) and
      approximately 500 M for K(+). 6. We propose that the gating shift and the block
      caused by Zn(2+) are mediated by two distinct sites and that the blocking site is
      located in the external mouth of the pore.

PMID- 11306656
TI  - Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their
      modulation by heteropolymerisation with Kir5.1.
AB  - 1. The inwardly rectifying potassium channel Kir5.1 appears to form functional
      channels only by coexpression with either Kir4.1 or Kir4.2. Kir4.1-Kir5.1
      heteromeric channels have been shown to exist in vivo in renal tubular epithelia.
      However, Kir5.1 is expressed in many other tissues where Kir4.1 is not found.
      Using Kir5.1-specific antibodies we have localised Kir5.1 expression in the
      pancreas, a tissue where Kir4.2 is also highly expressed. 2. Heteromeric Kir5.1
      Kir4.1 channels are significantly more sensitive to intracellular acidification
      than Kir4.1 currents. We demonstrate that this increased sensitivity is primarily
      due to modulation of the intrinsic Kir4.1 pH sensitivity by Kir5.1. 3. Kir4.2 was
      found to be significantly more pH sensitive (pK(a) = 7.1) than Kir4.1 (pK(a) =
      5.99) due to an additional pH-sensing mechanism involving the C-terminus. As a
      result, coexpression with Kir5.1 does not cause a major shift in the pH
      sensitivity of the heteromeric Kir4.2-Kir5.1 channel. 4. Cell-attached single
      channel analysis of Kir4.2 revealed a channel with a high open probability (P(o)
      > 0.9) and single channel conductance of approximately 25 pS, whilst coexpression
      with Kir5.1 produced novel bursting channels (P(o) < 0.3) and a principal
      conductance of approximately 54 pS with several subconductance states. 5. These
      results indicate that Kir5.1 may form heteromeric channels with Kir4.2 in tissues
      where Kir4.1 is not expressed (e.g. pancreas) and that these novel channels are
      likely to be regulated by changes in intracellular pH. In addition, the extreme
      pH sensitivity of Kir4.2 has implications for the role of this subunit as a
      homotetrameric channel.

PMID- 11306657
TI  - Unitary synaptic currents between lacunosum-moleculare interneurones and
      pyramidal cells in rat hippocampus.
AB  - 1. Unitary inhibitory postsynaptic currents (uIPSCs) were characterised between
      23 synaptically coupled interneurones at the border of stratum radiatum and
      lacunosum-moleculare (LM) and CA1 pyramidal cells (PYR) using dual whole-cell
      recordings and morphological identification in rat hippocampal slices. 2. LM
      interneurones presented a morphology typical of stellate cells, with a fusiform
      soma as well as dendritic and axonal arborisations in stratum radiatum and
      lacunosum-moleculare. 3. Single spikes in interneurones triggered uIPSCs in
      pyramidal cells that were blocked by the GABA(A) antagonist bicuculline and
      mediated by a chloride conductance. The latency, rise time, duration and decay
      time constant of uIPSCs were a function of amplitude in all pairs, suggesting a
      homogeneity in the population sampled. 4. During paired pulse stimulation,
      individual LM-PYR connections exhibited facilitation or depression. The paired
      pulse ratio was inversely related to the amplitude of the first response. The
      transition from facilitation to depression occurred at 26 % of the maximal
      amplitude of the first uIPSC. Paired pulse depression was not modified by CGP
      55845 and thus was GABA(B) receptor independent. 5. CGP 55845 failed to modify
      the amplitude of uIPSCs, suggesting an absence of tonic presynaptic GABA(B)
      inhibition at LM-PYR connections. 6. Increasing GABA release by repetitive
      activation of interneurones failed to induce GABA(B) IPSCs. With extracellular
      minimal stimulation, increasing stimulation intensity above threshold, or
      repetitive activation, evoked GABA(B) IPSCs, probably as a result of coactivation
      of several GABAergic fibres. 7. Thus, dendritic inhibition by LM interneurones
      involves GABA(A) uIPSCs with kinetics dependent on response amplitude and subject
      to GABA(B)-independent paired pulse plasticity.

PMID- 11306658
TI  - Slow recovery from inactivation regulates the availability of voltage-dependent
      Na(+) channels in hippocampal granule cells, hilar neurons and basket cells.
AB  - 1. Fundamental to the understanding of CNS function is the question of how
      individual neurons integrate multiple synaptic inputs into an output consisting
      of a sequence of action potentials carrying information coded as spike frequency.
      The availability for activation of neuronal Na(+) channels is critical for this
      process and is regulated both by fast and slow inactivation processes. Here, we
      have investigated slow inactivation processes in detail in hippocampal neurons.
      2. Slow inactivation was induced by prolonged (10-300 s) step depolarisations to 
      10 mV at room temperature. In isolated hippocampal dentate granule cells (DGCs),
      recovery from this inactivation was biexponential, with time constants for the
      two phases of slow inactivation tau(slow,1) and tau(slow,2) ranging from 1 to 10
      s and 20 to 50 s, respectively. Both (slow,1) and tau(slow,2) were related to the
      duration of prior depolarisation by a power law function of the form tau(t) = a
      (t/a)b, where t is the duration of the depolarisation, a is a constant kinetic
      setpoint and b is a scaling power. This analysis yielded values of a = 0.034 s
      and b = 0.62 for tau(slow,1) and a = 24 s and b = 0.30 for tau(slow,2) in the
      rat. 3. When a train of action potential-like depolarisations of different
      frequencies (50, 100, 200 Hz) was used to induce inactivation, a similar
      relationship was found between the frequency of depolarisation and both
      tau(slow,1) and tau(slow,2) (a = 0.58 s, b = 0.39 for tau(slow,1) and a = 3.77 s
      and b = 0.42 for tau(slow,2)). 4. Using nucleated patches from rat hippocampal
      slices, we have addressed possible cell specific differences in slow
      inactivation. In fast-spiking basket cells a similar scaling relationship can be
      found (a = 3.54 s and b = 0.39) as in nucleated patches from DGCs (a = 2.3 s and
      b = 0.48) and non-fast-spiking hilar neurons (a = 2.57 s and b = 0.49). 5.
      Likewise, comparison of human and rat granule cells showed that properties of
      ultra-slow recovery from inactivation are conserved across species. In both
      species ultra-slow recovery was biexponential with both tau(slow,1) and
      tau(slow,2) being related to the duration of depolarisation t, with a = 0.63 s
      and b = 0.44 for tau(slow,1) and a = 25 s and b = 0.37 for tau(slow,2) for the
      human subject. 6. In summary, we describe in detail how the biophysical
      properties of Na(+) channels result in a complex interrelationship between
      availability of sodium channels and membrane potential or action potential
      frequency that may contribute to temporal integration on a time scale of seconds
      to minutes in different types of hippocampal neurons.

PMID- 11306659
TI  - Ligand sensitivity of the 2 subunit from the bovine cone cGMP-gated channel is
      modulated by protein kinase C but not by calmodulin.
AB  - 1. Homomeric cyclic nucleotide-gated (CNG) channels composed of alpha2 subunits
      from bovine cone photoreceptors were heterologously expressed in the human
      embryonic kidney (HEK) 293 cell line. Modulation of cGMP sensitivity by protein
      kinase C (PKC)-mediated phosphorylation and by binding of calmodulin (CaM) was
      investigated in inside-out patches. 2. A peptide encompassing the putative CaM
      binding site within the N-terminus of the channel protein binds Ca(2+)-CaM with
      high affinity, yet the ligand sensitivity of alpha2 channels is not modulated by
      CaM. 3. PKC-mediated phosphorylation increased the activation constant (K(1/2))
      for cGMP from 19 to 56 microM and decreased the Hill coefficient (from 2.5 to
      1.5). The change in ligand sensitivity involves phosphorylation of the serine
      residues S577 and S579 in the cGMP-binding domain. The increase in K(1/2) was
      completely abolished in mutant channels in which the two serine residues were
      replaced by alanine. 4. An antibody specific for the delta isoform of PKC
      strongly labels the cone outer segments. 5. Modulation of cGMP affinity of bovine
      alpha2 CNG channels by phosphorylation could play a role in the regulation of
      photoreceptor sensitivity.

PMID- 11306660
TI  - Functional diversity and developmental changes in rat neuronal kainate receptors.
AB  - 1. Whole-cell currents evoked by kainate and the GluR5-selective agonist (RS)-2
      amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl)propanoic acid (ATPA) were used to
      compare the physiological properties of kainate receptors expressed by neurons
      from rat hippocampus, spinal cord and dorsal root ganglia. 2. In contrast to
      kainate, which evoked desensitizing currents with similar decay rates and steady
      state components in all three cell types, responses to ATPA were distinctly
      different in the three cell populations. Currents evoked by ATPA displayed a
      significant steady-state component in hippocampal neurons, but decayed rapidly to
      baseline in dorsal root ganglion (DRG) cells. ATPA failed to evoke current in
      many of the spinal neurons. 3. ATPA caused steady-state desensitization in DRG
      cells with an IC50 of 41 nM. Recovery from desensitization of DRG cell receptors
      by ATPA was significantly slower than for any previously described agonist. In
      contrast, hippocampal kainate receptors recovered from desensitization by ATPA
      within a few seconds. 4. Half-maximal activation of kainate receptors in
      hippocampal neurons required 938 nM ATPA. In DRG cells treated with concanavalin
      A the EC50 for ATPA was 341 nM. ATPA evoked current in embryonic hippocampal
      neurons but with lower amplitude relative to kainate than in cultured postnatal
      neurons. 5. Collectively, these results highlight functional differences between
      neuronal kainate receptors that may reflect their distinct subunit composition
      and their diverse roles in synaptic transmission.

PMID- 11306661
TI  - Adenosine A(2A) receptor enhances GABA(A)-mediated IPSCs in the rat globus
      pallidus.
AB  - 1. The actions of adenosine A(2A) receptor agonists were examined on GABAergic
      synaptic transmission in the globus pallidus (GP) in rat brain slices using whole
      cell patch-clamp recording. GP neurones were characterized into two major groups,
      type I and type II, according to the degree of time-dependent hyperpolarization
      activated inward rectification and the size of input resistance. 2. The A(2A)
      receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido-
      adenosine (CGS21680; 0.3-3 microM) enhanced IPSCs evoked by stimulation within
      the GP. The actions of CGS21680 were blocked by the A(2A) antagonists (E)-8-(3,4
      dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837) and 4-(2-[7-amino-2-(2
      furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385). 3.
      The CGS21680-induced increase in IPSCs was associated with a reduction in paired
      pulse facilitation. CGS21680 (0.3 microM) increased the frequency of miniature
      IPSCs (mIPSCs) without affecting mIPSC amplitude. These observations demonstrated
      that the enhancement of IPSCs in the GP was attributable to presynaptic, but not
      postsynaptic, A(2A) receptors. 4. The results suggest that A(2A) receptors in the
      GP serve to inhibit GP neuronal activity, thereby disinhibiting subthalamic
      nucleus neurone activity. Thus, the A(2A) receptor-mediated presynaptic
      regulation in the GP, together with the A(2A) receptor-mediated intrastriatal
      presynaptic control of GABAergic neurotransmission described previously, may play
      a crucial role in controlling the neuronal functions of basal ganglia. This A(2A)
      receptor-mediated presynaptic dual control in the striatopallidal pathway could
      also afford the mode of action of A(2A) antagonists for ameliorating the symptoms
      of Parkinson's disease in an animal model.

PMID- 11306662
TI  - Voltage-dependent flickery block of an open cystic fibrosis transmembrane
      conductance regulator (CFTR) channel pore.
AB  - 1. Fast flickery block of the cystic fibrosis transmembrane conductance regulator
      (CFTR) was studied with cell-attached and whole-cell patch-clamp recordings from
      mouse NIH3T3 cells stably expressing a mutant CFTR channel, K1250A-CFTR. This
      mutant CFTR channel, once open, can stay open for minutes. Within a prolonged
      opening, the kinetics of fast flickery closures can be readily quantified. 2.
      Flickering block of K1250A-CFTR channels was voltage dependent since the open
      probability within an opening burst decreased as the membrane was hyperpolarized.
      3. Mean open time (tau(o)) and mean closed time (tau(c)), obtained from single
      channel kinetic analysis, were corrected for missed events. Our data show that
      corrected tau(c) was voltage dependent while corrected tau(o) exhibited little
      voltage dependence. Results from whole-cell current relaxation upon voltage jump
      further indicate that tau(c) at a membrane potential of -100 mV was at least 10
      fold longer than that at +100 mV. 4. tau(c), but not tau(o), was sensitive to
      external permeant anions. After complete replacement of external Cl(-) with
      impermeant anions, tau(c) showed little voltage dependence and approximated a
      value observed under strong hyperpolarization in the presence of high external
      permeant anions. These results suggest that the resident time of the blocker is
      prolonged by conditions (i.e. hyperpolarization or the absence of external
      permeant anions) that deplete Cl(-) in the CFTR pore. 5. Results from macroscopic
      current noise analysis of both wild-type CFTR and K1250A-CFTR channels further
      confirm the voltage dependence and Cl(-) sensitivity of the fast flickery block
      observed with single-channel analysis. 6. We conclude that the voltage dependence
      of the flickery block in CFTR is mainly due to the voltage-dependent occupancy of
      an anion-binding site in the channel pore by trans-anions. The blocker acquires a
      voltage-dependent off rate through an electrostatic interaction with Cl(-) in the
      pore.

PMID- 11306663
TI  - Renal proximal tubule function is preserved in Cftr(tm2cam) deltaF508 cystic
      fibrosis mice.
AB  - 1. Changes in proximal tubule function have been reported in cystic fibrosis
      patients. The aim of this study was to investigate proximal tubule function in
      the Cftr(tm2cam)deltaF508 cystic fibrosis (CF) mouse model. A range of techniques
      were used including renal clearance studies, in situ microperfusion, RT-PCR and
      whole-cell patch clamping. 2. Renal Na(+) clearance was similar in wild-type (1.4
      +/- 0.3 microl min(-1), number of animals, N = 12) and CF mice (1.6 +/- 0.4
      microl min(-1), N = 7) under control conditions. Acute extracellular volume
      expansion resulted in significant natriuresis in wild-type (7.0 +/- 0.8 microl
      min(-1), N = 8) and CF mice (9.3 +/- 1.4 microl min(-1), N = 9); no difference
      between genotypes was observed. 3. In situ microperfusion revealed that fluid
      absorptive rate (Jv) was similar under control conditions between wild-type (2.2
      +/- 0.4 nl mm(-1) min(-1), n = 10) and CF mice (1.9 +/- 0.3 nl mm(-1) min(-1), n
      = 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate
      caused no significant change in Jv in either wild-type (2.6 +/- 0.7 nl mm(-1)
      min(-1), n = 10) or Cftr(tm2cam)deltaF508 mice (2.0 +/- 0.5 nl mm(-1) min(-1), n
      = 10). 4. CFTR expression was confirmed in samples of outer cortex using RT-PCR.
      However, no evidence for functional CFTR was obtained when outer cortical cells
      were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch
      clamping. 5. In conclusion, no functional deficit in proximal tubule function was
      found in Cftr(tm2cam)deltaF508 mice. This may be a consequence of a lack of whole
      cell cAMP-dependent Cl(-) conductance in mouse proximal tubule cells.

PMID- 11306664
TI  - An experimental test of the role of postsynaptic calcium levels in determining
      synaptic strength using perirhinal cortex of rat.
AB  - 1. We have investigated the prediction of a relationship between the magnitude of
      activity-dependent increases in postsynaptic calcium and both the magnitude and
      direction of synaptic plastic change in the central nervous system. 2. Activity
      dependent increases in calcium were buffered to differing degrees using a range
      of concentrations of EGTA and the effects on synaptic plasticity were assessed.
      Activity-dependent synaptic plasticity was induced during whole-cell recording in
      rat perirhinal cortex in vitro. In control conditions (0.5 mM EGTA) low frequency
      stimulation (LFS; 200 stimuli) delivered to neurones held at -40 or -70 mV
      induced long-term depression (LTD) or, at -10 mV, induced long-term potentiation
      (LTP). 3. The relationship between EGTA concentration (0.2 to 10 mM) and the
      magnitude of LTD was examined. This relationship described a U-shaped curve, as
      predicted by models of synaptic plasticity. This provides strong evidence that
      the magnitude of LTD is determined by the magnitude of the increase in
      intracellular calcium concentration. 4. LFS paired with depolarisation to -10 mV
      induced LTD, no change or LTP as activity-dependent postsynaptic calcium levels
      were allowed to increase progressively by the use of progressively lower
      concentrations of buffer (10 to 0.2 mM EGTA). 5. We investigated if the lack of
      plasticity that occurs at the transition between LTD and LTP is due to induction
      of both of these processes with zero net change, or is due to neither LTD nor LTP
      being induced. These experiments were possible as LTP but not LTD was blocked by
      the protein kinase inhibitor staurosporine while LTD but not LTP was blocked by
      the mGlu receptor antagonist MCPG. At the transition between LTD and LTP,
      blocking LTP mechanisms did not uncover LTD whilst blocking LTD mechanisms did
      not uncover LTP. This suggests that the transition between LTD and LTP is due to
      the lack of induction of both of these processes and also suggests that these two
      processes are induced independently of one another.

PMID- 11306665
TI  - Microdialysis perfusion of 5-HT into hypoglossal motor nucleus differentially
      modulates genioglossus activity across natural sleep-wake states in rats.
AB  - 1. Serotonin (5-hydroxytryptamine, 5-HT) excites hypoglossal (XII) motoneurons in
      reduced preparations, and it has been suggested that withdrawal of 5-HT may
      underlie reduced genioglossus (GG) muscle activity in sleep. However, systemic
      administration of 5-HT agents in humans has limited effects on GG activity.
      Whether 5-HT applied directly to the XII motor nucleus increases GG activity in
      an intact preparation either awake or asleep has not been tested. 2. The aim of
      this study was to develop a novel freely behaving animal model for in vivo
      microdialysis of the XII motor nucleus across sleep-wake states, and test the
      hypothesis that 5-HT application will increase GG activity. 3. Eighteen rats were
      implanted with electroencephalogram and neck muscle electrodes to record sleep
      wake states, and GG and diaphragm electrodes for respiratory muscle recording.
      Microdialysis probes were implanted into the XII motor nucleus and perfused with
      artificial cerebrospinal fluid (ACSF) or 10 mM 5-HT. 4. Normal decreases in GG
      activity occurred from wakefulness to non-rapid eye movement (non-REM) and REM
      sleep with ACSF (P < 0.01). Compared to ACSF, 5-HT caused marked GG activation
      across all sleep-wake states (increases of 91-251 %, P < 0.015). Importantly, 5
      HT increased sleeping GG activity to normal waking levels for as long as 5-HT was
      applied (3-5 h). Despite tonic stimulation by 5-HT, periods of phasic GG
      suppression and excitation occurred in REM sleep compared with non-REM. 5. The
      results show that sleep-wake states differentially modulate GG responses to 5-HT
      at the XII motor nucleus. This animal model using in vivo microdialysis of the
      caudal medulla will enable the determination of neural mechanisms underlying
      pharyngeal motor control in natural sleep.

PMID- 11306666
TI  - Changes in cat medullary neurone firing rates and synchrony following induction
      of respiratory long-term facilitation.
AB  - 1. Long-term facilitation is a respiratory memory expressed as an increase in
      motor output lasting more than an hour. This change is induced by repeated
      hypoxia, stimulation of carotid chemoreceptors, or electrical stimulation of the
      carotid sinus nerve or brainstem mid-line. The present work addressed the
      hypothesis that persistent changes in medullary respiratory neural networks
      contribute to long-term facilitation. 2. Carotid chemoreceptors were stimulated
      by close arterial injection of CO(2)-saturated saline solution. Phrenic nerve
      efferent activity and up to 30 single medullary neurones were recorded
      simultaneously in nucleus tractus solitarii (NTS) including the dorsal
      respiratory group (DRG), Botzinger-ventral respiratory group (Bot-VRG), and
      nucleus raphe obscurus of nine adult cats, anaesthetized, injected with a
      neuromuscular blocking agent, vagotomized and artificially ventilated. 3. The
      firing rates of 87 of 105 neurones (83 %) changed following induction of long
      term facilitation. Nine of eleven DRG and Bot-VRG putative premotor inspiratory
      neurones had increased firing rates with long-term facilitation. Fourteen of
      twenty-one raphe obscurus neurones with control firing rates less than 4 Hz had
      significant long-term increases in activity. 4. Cross-correlogram analysis
      suggested that there were changes in effective connectivity of neuron pairs with
      long-term facilitation. Joint peristimulus time histograms and pattern detection
      methods used with 'gravity' analysis also detected changes in short time scale
      correlations associated with long-term facilitation. 5. The results suggest that
      changes in firing rates and synchrony of VRG and DRG premotor neurones and
      altered effective connectivity among other functionally antecedent elements of
      the medullary respiratory network contribute to the expression of long-term
      facilitation.

PMID- 11306667
TI  - Effects of ADP on sarcoplasmic reticulum function in mechanically skinned
      skeletal muscle fibres of the rat.
AB  - 1. The sarcoplasmic reticulum (SR) Ca(2+) content (expressed in terms of
      endogenous SR Ca(2+) content under physiologically resting conditions and
      measured from caffeine-induced force responses) and the effective rates of the SR
      Ca(2+) pump and SR Ca(2+) leak (measured from the temporal changes in SR Ca(2+)
      content) were determined in mechanically skinned skeletal muscle fibres of the
      rat at different [ADP] (< 0.10 microM to 1.04 mM). 2. The estimated SR Ca(2+)
      pump rate at 200 nM Ca(2+) did not change when [ADP] increased from below 0.10
      microM to 10 microM but decreased by about 30 % when [ADP] increased from 10
      microM to 1.04 mM. 3. The rate constant of SR Ca(2+) leak increased markedly with
      rising [ADP] when [Ca(2+)] in solution was 200 nM (apparent dissociation constant
      Kd(ADP) = 64 +/- 27 microM). Decreasing the [Ca(2+)] in solution from 200 nM to <
      10 nM significantly increased the leak rate constant at all [ADP]. The SR Ca(2+)
      leak rate constant could be significantly reduced by blocking the SR Ca(2+) pump
      with 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ). 4. The decrease in the SR Ca(2+)
      pump rate and the increase in the rate constant of SR Ca(2+) leak when the [ADP]
      increased from < 0.10 microM to 1.04 mM caused a 4.4-fold decrease in SR Ca(2+)
      loading ability at 200 nM Ca(2+). 5. The results can be fully explained by a
      mechanism whereby the presence of ADP causes a marked increase in the ADP
      sensitive fraction of the phosphorylated pump protein, which can act as a Ca(2+)
      Ca(2+) exchanger and demonstrates that ADP is an important modulator of SR
      function in skeletal muscle.

PMID- 11306668
TI  - Charge movements in intact amphibian skeletal muscle fibres in the presence of
      cardiac glycosides.
AB  - 1. Intramembrane charge movements were examined in intact voltage-clamped
      amphibian muscle fibres following treatment with cardiac glycosides in the
      hypertonic gluconate-containing solutions hitherto reported to emphasise the
      features of q(gamma) at the expense of q(beta) charge. 2. The application of
      chlormadinone acetate (CMA) at concentrations known selectively to block Na(+)
      K(+)-ATPase conserved the steady-state voltage dependence of intramembrane
      charge, contributions from delayed (q(gamma)) charging transients, and their
      inactivation characteristics brought about by shifts in holding potential. 3. The
      addition of either ouabain (125, 250 or 500 nM) or digoxin (5 nM) at
      concentrations previously reported additionally to influence excitation
      contraction coupling similarly conserved the steady-state charge-voltage
      relationships, Q(V), in fully polarised fibres to give values of maximum charge,
      Q(max), transition voltage, V*, and steepness factor, k, that were consistent
      with a persistent q component as reported on earlier occasions (Q(max)
      approximately = 25-27 nC F-1, V* approximately = -45 to -50 mV, k approximately =
      7-9 mV). 4. In both cases shifts in holding potential from -90 to -50 mV produced
      a partial inactivation that separated steeply and more gradually voltage
      dependent charge components in agreement with previous characterisations. 5.
      However, charge movements that were observed in the presence of either digoxin or
      ouabain were monotonic decays in which delayed (q(gamma)) transients could not be
      distinguished from the early charging records. These features persisted despite
      the further addition of chlormadinone acetate over a 10-fold concentration range
      (5-50 microM) known to displace ouabain from the Na(+)-K(+)-ATPase. 6. Ouabain
      (500 nM) restored the steady-state charge movement that was previously abolished
      by the addition of 2.0 mM tetracaine in common with previous results of using
      ryanodine receptor (RyR)-specific agents. 7. Perchlorate (8.0 mM) restored the
      delayed 'on' relaxations and increased the prominence of the 'off' decays
      produced by q(gamma) charge following treatment with cardiac glycosides. This was
      accompanied by a negative (approximately 10-15 mV) shift in the steady-state
      charge-voltage relationship but an otherwise conserved maximum charge, Q(max),
      and steepness factor, k, in parallel with previously reported effects of
      perchlorate following treatments with RyR-specific agents. 8. The features of
      cardiac glycoside action thus parallel those of other agents that act on RyR
      Ca(2+) release channels yet influence the kinetics but spare the steady-state
      properties of intramembrane charge.

PMID- 11306669
TI  - Effect of pulmonary stretch receptor feedback and CO(2) on upper airway and
      respiratory pump muscle activity in the rat.
AB  - 1. Our purpose was to examine the effects of chemoreceptor stimulation and lung
      inflation on neural drive to tongue protrudor and retractor muscles in the rat.
      2. Inspiratory flow, tidal volume, transpulmonary pressure, compliance and
      electromyographic (EMG) activity of genioglossus (GG), hyoglossus (HG) and
      inspiratory intercostal (IIC) muscles were studied in 11 anaesthetized,
      tracheotomized and spontaneously breathing rats. Mean EMG activity during
      inspiration was compared with mean EMG activity during an occluded inspiration,
      at each of five levels of inspired CO(2) (0, 3, 6, 9 and 12 %). 3. Lung inflation
      suppressed EMG activity in all muscles, with the effect on both tongue muscles
      exceeding that of the intercostal muscles. Static elevations of end-expiratory
      lung volume evoked by 2 cmH(2)O positive end-expiratory pressure (PEEP) had no
      effect on tongue muscle activity. 4. Despite increasing inspiratory flow, tidal
      volume and transpulmonary pressure, the inhibition of tongue muscle activity by
      lung inflation diminished as arterial PCO2 (P(a),CO(2)) increased. 5. The onset
      of tongue muscle activity relative to the onset of IIC muscle activity advanced
      with increases in P(a),CO(2) but was unaffected by lung inflation. This suggests
      that hypoglossal and external intercostal motoneuron pools are controlled by
      different circuits or have different sensitivities to CO(2), lung inflation
      and/or anaesthetic agents. 6. We conclude that hypoglossal motoneuronal activity
      is more strongly influenced by chemoreceptor-mediated facilitation than by lung
      volume-mediated inhibition. Hypoglossal motoneurons driving tongue protrudor and
      retractor muscles respond identically to these stimuli.

PMID- 11306670
TI  - Respiratory activity in glossopharyngeal, vagus and accessory nerves and
      pharyngeal constrictors in newborn rat in vitro.
AB  - 1. Previously, in a brainstem-spinal cord-rib preparation from neonatal rats we
      demonstrated that a decrement in extracellular pH (from about 7.4 to 7.1) caused
      expiratory activity in an internal intercostal muscle (IIM) during the first half
      of the expiratory phase (Ea). As the initial step in finding nerves or muscles
      firing during the second half of the expiratory phase (Eb), the patterns of
      activity in the glossopharyngeal, vagus and accessory nerves were examined in the
      present study. 2. Since the emerging motor rootlets of these three nerves (> 20;
      collected into about 10 bundles before the jugular foramen) are distributed in a
      continuous fashion from rostral to caudal levels of the brainstem, visual
      identification was impossible. Therefore, antidromic compound action potentials
      evoked by stimulation of the glossopharyngeal nerve (IX), the pharyngeal branch
      of the vagus nerve (PhX), the superior laryngeal nerve (SLN), the cervical vagus
      nerve (CX) and the accessory nerve (XI) were recorded from the peripheral stumps
      of the various rootlets. Nerve rootlets could be categorised into rostral,
      intermediate and caudal groups (rostIX-XI, intIX-XI, caudIX-XI). The rostIX-XI
      rootlets showed their largest potential on IX stimulation, while the intIX-XI and
      caudIX-XI rootlets showed their largest potentials on CX stimulation. The intIX
      XI rootlets showed larger potentials on PhX and SLN stimulation than the caudIX
      XI rootlets. 3. Activity was recorded simultaneously from the central stumps of
      the rootlets in the above three groups. Most rootlets showed inspiratory bursts.
      Under low pH conditions, all representatives of group rostIX-XI, most of intIX-XI
      and about half of caudIX-XI showed additional bursts during the Ea phase. Groups
      intIX-XI and caudIX-XI but not rostIX-XI also showed discrete bursts during the
      Eb phase in some preparations. In general, expiratory activity was prominent in
      intIX-XI. The spinal branch of XI showed no consistent respiratory activity. 4.
      Since the intIX-XI rootlets showed Eb bursts and large antidromic potentials on
      stimulation of PhX and SLN (which innervate the inferior pharyngeal constrictor
      muscle (IPC)), electromyograms were recorded from the rostral and caudal parts of
      IPC (rIPC and cIPC). Under low pH conditions, cIPC showed bursts during the Ea
      and Eb phases, while rIPC showed bursts predominantly during the Eb phase. 5.
      These results indicate that recording from rIPC would be a useful way of
      examining the neuronal mechanisms responsible for Eb phase activity.

PMID- 11306671
TI  - Reflex vascular responses to independent changes in left ventricular end
      diastolic and peak systolic pressures and inotropic state in anaesthetised dogs.
AB  - 1. Ventricular mechanoreceptors are known to exist and can when stimulated induce
      reflex vasodilatation, but the nature of the effective stimuli and the
      physiological role of the reflex remain to be established. 2. Dogs were
      anaesthetised with chloralose and a cardiopulmonary bypass established.
      Ventricular pressures were separated from those in the aortic root and coronary
      arteries by a balloon inflated in the ventricular outflow tract. Ventricular
      filling was controlled by adjusting the rate of inflow of blood through an apical
      cannula and peak pressure by regulating the outflow pressure from the same
      cannula. Carotid and aortic pressures were also controlled and vascular
      resistance was assessed from changes in perfusion pressure (constant flow
      conditions) to the descending abdominal aorta. 3. Increased coronary or carotid
      sinus pressure induced a significant vasodilatation. Changes in ventricular peak
      systolic pressure, without associated changes in end-diastolic pressure, had no
      significant effect on vascular resistance. In contrast, changes in end-diastolic
      pressure did induce vasodilatation that, although small, was proportional to the
      magnitude of the end-diastolic pressure change. 4. Changes in ventricular
      inotropic state induced by dobutamine infusion or by stimulation of efferent
      cardiac sympathetic nerves did not induce significant responses. Furthermore, the
      combined effects of reduced ventricular filling and increased inotropic state
      were also ineffective in inducing responses. 5. We conclude that, to induce
      reflex responses, the only effective stimulus to ventricular mechanoreceptors was
      an increase in filling. Compared with other mechanoreflexes, however, responses
      to ventricular distension were small and seem unlikely to be of importance except
      perhaps during abnormal ventricular distension.

PMID- 11306672
TI  - Modulation of primary afferent discharge by dynamic and static gamma motor axons
      in cat muscle spindles in relation to the intrafusal fibre types activated.
AB  - 1. Recordings were made from muscle spindle primary afferents from medial
      gastrocnemius and soleus muscles of the cat to study the modulating effects of
      varying gamma-motor stimulation frequency at constant muscle length. Stimulus
      trains had a mean frequency of 50 Hz and were sinusoidally frequency modulated at
      1 Hz, with an amplitude of modulation of +/- 5 to +/- 30 Hz. 2. When dynamic
      gamma-axons (gamma(d)) were selected for their pure effect on bag(1) fibres, they
      were found to have very little modulating effect on afferent firing. 3. Static
      gamma-axons (gamma(s)) were tested with a random stimulus and correlation method
      to determine whether they acted purely on bag(2) fibres, purely on chain fibres
      or on both together. Pure bag(2) gamma(s)-axons had weak modulating effects with
      large values of phase lag. Pure chain connections were effective in modulating
      with very little phase lag, but their mean gain was low. Mixed bag(2) and chain
      axons were most effective and showed phase shifts proportional to gain. 4. The
      effects of muscle length changes recorded previously from locomotor movements
      were also tested, with and without accompanying stimulation of mixed gamma(s)
      axons with pulse trains recorded from gamma(s)-axons. This gamma(s) stimulation
      had a powerful effect in increasing afferent discharge during muscle shortening.
      The difference in afferent firing between the stimulated and non-stimulated
      conditions accurately predicted the profile of the gamma(s) stimulation. 5. The
      results are discussed in relation to the ways in which the gamma-motor system may
      be used in natural movements.

PMID- 11306673
TI  - Latency and duration of stimulation of human muscle protein synthesis during
      continuous infusion of amino acids.
AB  - 1. The aim of this study was to describe the time course of the response of human
      muscle protein synthesis (MPS) to a square wave increase in availability of amino
      acids (AAs) in plasma. We investigated the responses of quadriceps MPS to a
      approximately 1.7-fold increase in plasma AA concentrations using an intravenous
      infusion of 162 mg (kg body weight)(-1) h(-1) of mixed AAs. MPS was estimated
      from D3-leucine labelling in protein after a primed, constant intravenous
      infusion of D3-ketoisocaproate, increased appropriately during AA infusion. 2.
      Muscle was separated into myofibrillar, sarcoplasmic and mitochondrial fractions.
      MPS, both of mixed muscle and of fractions, was estimated during a basal period
      (2.5 h) and at 0.5-4 h intervals for 6 h of AA infusion. 3. Rates of mixed MPS
      were not significantly different from basal (0.076 +/- 0.008 % h(-1)) in the
      first 0.5 h of AA infusion but then rose rapidly to a peak after 2 h of
      approximately 2.8 times the basal value. Thereafter, rates declined rapidly to
      the basal value. All muscle fractions showed a similar pattern. 4. The results
      suggest that MPS responds rapidly to increased availability of AAs but is then
      inhibited, despite continued AA availability. These results suggest that the fed
      state accretion of muscle protein may be limited by a metabolic mechanism
      whenever the requirement for substrate for protein synthesis is exceeded.

PMID- 11306674
TI  - Cyanovirin-N defines a new class of antiviral agent targeting N-linked, high
      mannose glycans in an oligosaccharide-specific manner.
AB  - Herein we report that the novel HIV-inactivating protein cyanovirin-N (CV-N)
      targets specific, N-linked high-mannose oligosaccharides found on the viral
      envelope of HIV-1. First, we released the oligosaccharides by PnGase-treatment of
      HIV-gp120 (containing high-mannose, hybrid-type and complex-type
      oligosaccharides) or HSV-1 gC (containing only complex-type). Then, in an
      affinity chromatographic system, we found that CV-N bound to the free
      oligosaccharides from gp120 but not from gC-1, suggesting that high-mannose
      oligosaccharides constitute a target structure for CV-N. This was supported by
      the affinity of CV-N for high-mannose glycans released from gp120 by endo-H as
      well as high-mannose glycans released from castanospermine-treated HSV-1 gC.
      Furthermore, free Man-8 or Man-9 oligosaccharides partially inhibited the binding
      of CV-N to gp120, although neither oligosaccharides smaller than Man-7 nor
      monosaccharides interfered with CV-N/gp120 interaction, thereby establishing the
      oligosaccharide-specific affinity of CV-N to high-mannose glycans. This affinity
      for high-mannose oligosaccharides may explain the broad antiviral activity of CV
      N against human and primate immunodeficiency retroviruses as well as certain
      other viruses that carry these oligosaccharides.

PMID- 11306675
TI  - The CB(1) cannabinoid receptor of astrocytes is coupled to sphingomyelin
      hydrolysis through the adaptor protein fan.
AB  - Cannabinoids exert most of their effects through the CB(1) receptor. This G
      protein-coupled receptor signals inhibition of adenylyl cyclase, modulation of
      ion channels, and stimulation of mitogen- and stress-activated protein kinases.
      In this article, we report that Delta(9)-tetrahydrocannabinol (THC), the major
      active component of marijuana, induces sphingomyelin hydrolysis in primary
      astrocytes but not in other cells expressing the CB(1) receptor, such as primary
      neurons, U373 MG astrocytoma cells, and Chinese hamster ovary cells transfected
      with the CB(1) receptor cDNA. THC-evoked sphingomyelin breakdown in astrocytes
      was also exerted by the endogenous cannabinoid anandamide and the synthetic
      cannabinoid HU-210 and was prevented by the selective CB(1) antagonist SR141716.
      By contrast, the effect of THC was not blocked by pertussis toxin, pointing to a
      lack of involvement of G(i/o) proteins. A role for the adaptor protein FAN in
      CB(1) receptor-coupled sphingomyelin breakdown is supported by two observations:
      1) coimmunoprecipitation experiments show that the binding of FAN to the CB(1)
      receptor is enhanced by THC and prevented by SR141716; 2) cells expressing a
      dominant-negative form of FAN are refractory to THC-induced sphingomyelin
      breakdown. This is the first report showing that a G-protein-coupled receptor
      induces sphingomyelin hydrolysis through FAN and that the CB(1) cannabinoid
      receptor may signal independently of G(i/o) proteins.

PMID- 11306676
TI  - Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate
      receptor current.
AB  - Protein kinase-C (PKC) activation differentially affects currents from N-methyl-D
      aspartate (NMDA) type glutamate receptors depending upon their subunit
      composition. Experiments using chimeras initially indicated that the cytoplasmic
      C-terminal tails of NR2B (responsive to PKC) and NR2C (unresponsive to PKC)
      subunits contain the amino acid residues responsible for the observed disparity
      of PKC effects. However, truncation and point mutation experiments have suggested
      that PKC action on NMDA receptors may be entirely indirect, working via the
      phosphorylation of associated proteins. Here we suggest that PKC does, in fact,
      affect NR2B/NR1-011 NMDA currents by direct phosphorylation of the NR2B tail at
      residues S1303 and S1323. Replacement of either of these residues with Ala
      severely reduces PKC potentiation. To verify that S1303 and S1323 are sites of
      direct phosphorylation by PKC, synthetic peptides from the regions surrounding
      these sites were used as substrates for in vitro assays with purified rat brain
      PKC. These results indicate that PKC can directly phosphorylate S1303 and S1323
      in the NR2B C terminus, leading to enhanced currents through NMDA receptor
      channels. The direct action of PKC on certain NMDA receptor subtypes may be
      important in any physiological or pathological process where PKC and NR2B/NR1
      receptors interact.

PMID- 11306677
TI  - BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse
      agonist activity.
AB  - L-Glutamate (Glu) activates at least eight different G protein-coupled receptors
      known as metabotropic glutamate (mGlu) receptors, which mostly act as regulators
      of synaptic transmission. These receptors consist of two domains: an
      extracellular domain in which agonists bind and a transmembrane heptahelix region
      involved in G protein activation. Although new mGlu receptor agonists and
      antagonists have been described, few are selective for a single mGlu subtype.
      Here, we have examined the effects of a novel compound, BAY36-7620 [(3aS,6aS)- 6a
      Naphtalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on], on mGlu
      receptors (mGlu1-8), transiently expressed in human embryonic kidney 293 cells.
      BAY36-7620 is a potent (IC(50) = 0.16 microM) and selective antagonist at mGlu1
      receptors and inhibits >60% of mGlu1a receptor constitutive activity (IC(50) =
      0.38 microM). BAY36-7620 is therefore the first described mGlu1 receptor inverse
      agonist. To address the mechanism of action of BAY36-7620, Glu dose-response
      curves were performed in the presence of increasing concentrations of BAY36-7620.
      The results show that BAY36-7620 largely decreases the maximal effect of Glu.
      Moreover, BAY36-7620 did not displace the [(3)H]quisqualate binding from the Glu
      binding pocket, further indicating that BAY36-7620 is a noncompetitive mGlu1
      antagonist. Studies of chimeric receptors containing regions of mGlu1 and regions
      of DmGluA, mGlu2, or mGlu5, revealed that the transmembrane region of mGlu1 is
      necessary for activity of BAY36-7620. Transmembrane helices 4 to 7 are shown to
      play a critical role in the selectivity of BAY36-7620. This specific site of
      action of BAY36-7620 differs from that of competitive antagonists and indicates
      that the transmembrane region plays a pivotal role in the agonist-independent
      activity of this receptor. BAY36-7620 will be useful to further delineate the
      functional importance of the mGlu1 receptor, including its putative agonist
      independent activity.

PMID- 11306678
TI  - Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine in MRP2-deficient rats.
AB  - MRP2 is an apical transporter expressed in hepatocytes and the epithelial cells
      of the small intestine and kidney proximal tubule. It extrudes organic anions,
      conjugated compounds, and some uncharged amphipaths. We studied the transport of
      an abundant food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) in vitro, using an MRP2 transfected epithelial cell line (MDCK
      II) and intestinal explants from Wistar and MRP2-deficient TR(-) rats in Ussing
      chambers. In the experiments with the transfected cell line, we could demonstrate
      more than 3-fold higher transport from basolateral to apical than vice versa,
      whereas the transport in the parent cell line was equal in both directions. These
      results were confirmed in studies using isolated pieces of small intestine from
      Wistar and TR(-) rats in the Ussing chamber. Subsequent in vivo experiments
      demonstrated that after oral administration, absorption of PhIP was 2-fold higher
      in the TR(-) rat than in the Wistar rat. Consequently, PhIP tissue levels in
      several organs (liver, kidney, lung, and colon) were 1.7- to 4-fold higher 48 h
      after oral administration. MRP2 mediated transport of unchanged PhIP probably
      involves intracellular GSH, because GSH depletion by BSO-treatment in Wistar rats
      reduced intestinal secretion in the Ussing chamber to the same level as in TR(-)
      rats. In accordance, BSO treatment increased oral bioavailability in intact
      Wistar rats. This study shows for the first time that MRP2-mediated extrusion
      reduces oral bioavailability of a xenobiotic and protects against an abundant
      food-derived carcinogen.

PMID- 11306679
TI  - Zn(2+) induces stimulation of the c-Jun N-terminal kinase signaling pathway
      through phosphoinositide 3-Kinase.
AB  - Zn(2+), one of the most abundant trace metal ions in mammalian cells, modulates
      the functions of many regulatory proteins associated with a variety of cellular
      activities. In the central nervous system, Zn(2+) is highly localized in the
      cerebral cortex and hippocampus. It has been proposed to play a role in normal
      brain function as well as in the pathophysiology of certain neurodegenerative
      disorders. We here report that Zn(2+) induced stimulation of the c-Jun N-terminal
      kinase (JNK) pathway in mouse primary cortical cells and in various cell lines.
      Exposure of cells to Zn(2+) resulted in the stimulation of JNK and its upstream
      kinases including stress-activated protein kinase kinase and mitogen-activated
      protein kinase kinase kinase. Zn(2+) also induced stimulation of phosphoinositide
      3-kinase (PI3K) The Zn(2+)-induced JNK stimulation was blocked by LY294002, a
      PI3K inhibitor, or by a dominant-negative mutant of PI3Kgamma. Furthermore,
      overexpression of Rac1N17, a dominant negative mutant of Rac1, suppressed the
      Zn(2+)- and PI3Kgamma-induced JNK stimulation. The stimulatory effect of Zn(2+)
      on both PI3K and JNK was repressed by the free-radical scavenging agent N
      acetylcysteine. Taken together, our data suggest that Zn(2+) induces stimulation
      of the JNK signaling pathway through PI3K-Rac1 signals and that the free-radical
      generation may be an important step in the Zn(2+) induction of the JNK
      stimulation.

PMID- 11306680
TI  - Transcriptional induction of hepatic NADPH: cytochrome P450 oxidoreductase by
      thyroid hormone.
AB  - Studies were carried out to elucidate the mechanism whereby thyroid hormone (T3)
      induces NADPH:cytochrome P450 oxidoreductase (P450R) mRNA in rat liver in vivo.
      Northern blot analysis revealed that T3 treatment increases unspliced liver
      nuclear P450R RNA 4-fold within 8 h and that this induction precedes the
      induction of mature, cytoplasmic P450R RNA. Unspliced nuclear P450R RNA was
      suppressed below basal levels 24 h after T3 treatment, despite the continued
      presence of elevated circulating T3 levels. To determine whether the T3
      stimulated increase in nuclear P450R RNA reflects an increase in P450R
      transcription initiation, nuclear run-on transcription assays were carried out.
      T3 induced a 6- to 8-fold increase in P450R transcription rate within 12 h,
      sufficient to account for the observed increase in nuclear P450R precursor RNA,
      followed by a decrease back to basal transcription levels at 24 h, consistent
      with the nuclear RNA profile. Similar transcriptional increases were observed in
      nuclear run-on transcription studies using hybridization probes corresponding to
      nine different fragments of the P450R gene, spanning exon 2 to exon 16. Thus,
      P450R transcription initiation, not transcription elongation, is the T3-regulated
      event. Similar results were obtained during short (5 min) compared with long (45
      min) nuclear run-on transcription assays, suggesting that changes in nuclear RNA
      processing or regulated degradation do not contribute to the overall RNA
      induction. This finding was confirmed by the ability of the RNA polymerase
      inhibitor actinomycin D, administered in vivo, to block T3 induction of P450R
      transcriptional activity. We conclude that P450R transcription, rather than
      nuclear RNA processing or mRNA stabilization, is the primary mechanism whereby T3
      induces hepatic P450R mRNA.

PMID- 11306681
TI  - Molecular cloning, genomic positioning, promoter identification, and
      characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10.
AB  - We describe the cloning and expression of HSPDE4A10, a novel long form splice
      variant of the human cAMP phosphodiesterase PDE4A gene. The 825 amino acid
      HSPDE4A10 contains a unique N terminus of 46 amino acids encoded by a unique 5'
      exon. Exon-1(4A10) lies approximately 11 kilobase pairs (kb) downstream of exon
      1(4A4) and approximately 13.5 kb upstream of the PDE4A common exon 2. We identify
      a rat PDE4A10 ortholog and reveal a murine ortholog by nucleotide sequence
      database searching. PDE4A10 transcripts were detected in various human cell lines
      and tissues. The 5' sequence flanking exon-1(4A10) exhibited promoter activity
      with the minimal functional promoter region being highly conserved in the
      corresponding mouse genomic sequence. Transient expression of the engineered
      human PDE4A10 open reading frame in COS7 cells allowed detection of a 121-kDa
      protein in both soluble and particulate fractions. PDE4A10 was localized
      primarily to the perinuclear region of COS7 cells. Soluble and particulate forms
      exhibited similar K(m) values for cAMP hydrolysis (3-4 microM) and IC(50) values
      for inhibition by rolipram (50 nM) but the V(max) value of the soluble form was
      approximately 3-fold greater than that of the particulate form. At 55 degrees C,
      soluble HSPDE4A10 was more thermostable (T(0.5) = 11 min) than the particulate
      enzyme (T(0.5) = 5 min). HSPDE4A10 and HSPDE4A4B are shown here to be similar in
      size and exhibit similar maximal activities but differ with respect to
      sensitivity to inhibition by rolipram, thermostability, interaction with the SRC
      homology 3 domain of LYN, an SRC family tyrosyl kinase, and subcellular
      localization. We suggest that the unique N-terminal regions of PDE4A isoforms
      confer distinct properties upon them.

PMID- 11306682
TI  - Role of protein kinase Calpha in signaling from the histamine H(1) receptor to
      the nucleus.
AB  - Stimulation of histamine H(1) receptors produced a marked activation of inositol
      phospholipid hydrolysis, intracellular calcium mobilization, and stimulation of
      the c-fos promoter in CHO-H1 cells expressing the H(1) receptor at a level of 3
      pmol/mg protein. The latter response was determined using a luciferase-based
      reporter gene (pGL3). This response to histamine was not sensitive to inhibition
      by pertussis toxin but could be completely attenuated by the protein kinase C
      (PKC) inhibitor Ro-31-8220, or by 24-h pretreatment with the phorbol esters
      phorbol 12,13-dibutyrate or phorbol-12-myristate-13-acetate. Several isoforms of
      PKC can be detected in CHO-H1 cells (alpha, delta, epsilon, mu, iota, zeta) but
      only PKCalpha and PKCdelta were down-regulated by prolonged treatment with
      phorbol esters. Of the two isoforms that were down-regulated, only protein kinase
      Calpha was translocated to CHO-H1 cell membranes after stimulation with either
      histamine or phorbol esters. The PKC inhibitor Go 6976, which inhibits PKCalpha
      but not PKCdelta, was also able to significantly attenuate the c-fos-luciferase
      response to histamine. The mitogen-activated protein kinase kinase inhibitor PD
      98059 markedly inhibited the response to histamine, suggesting that the likely
      major target for PKCalpha was the mitogen-activated protein kinase pathway. These
      data suggest that the histamine H(1) receptor can signal to the nucleus via
      PKCalpha after activation of phospholipase Cbeta.

PMID- 11306683
TI  - Mutational analysis of the functional role of conserved arginine and lysine
      residues in transmembrane domains of the murine reduced folate carrier.
AB  - The reduced folate carrier (RFC1) plays a major role in the delivery of folates
      into mammalian cells. RFC1 is an anion exchanger with seven conserved positively
      charged amino acid residues within 12 predicted transmembrane domains. This
      article explores the role of these residues in transport function by the
      development of cell lines in which arginines and lysines in RFC1 were replaced
      with leucine by site-directed mutagenesis. Three cell lines transfected with
      R131L, R155L, or R366L all lacked activity, despite high levels of protein
      expression in the plasma membrane, suggesting the crucial role of these amino
      acid residues in RFC1 function. In several mutant carriers, R26L, R42L, and
      K332L, there was little or no change in the influx K(t) value for MTX or influx
      K(i) value for folic acid. However, the R26L, R42L, and K332L carriers had
      decreased affinity for reduced folates. This was most prominent for K404L, which
      had 11- and 4-fold increases in influx K(i) for 5-methyl-THF and 5-formyl-THF,
      respectively, compared with L1210 cells. The marked influx stimulation observed
      with wild-type carrier when extracellular chloride was decreased was
      significantly diminished when influx was mediated by the K404L carrier, but was
      only slightly decreased with the R26L, R42L, and K332L mutants. This suggested
      that the K404 residue may be a major site of inhibition by chloride in the wild
      type carrier. These studies indicate the important role that some positively
      charged residues within transmembrane domains of RFC1 play in RFC1 function.

PMID- 11306684
TI  - Expression of multiple subtypes of muscarinic receptors and cellular distribution
      in the human heart.
AB  - Five isoforms of the muscarinic acetylcholine receptor (mAChR) have been
      identified by molecular cloning and designated m(1)-m(5), of which four
      correspond to the functional subtypes M(1), M(2), M(3), and M(4) in primary
      tissues. The presence of M(5) receptors in tissues remains uncertain. The present
      study was designed to explore the diversity and cellular distribution of various
      mAChR subtypes in human hearts. Competition binding of [N-methyl-(3)H]
      scopolamine methyl chloride with various mAChR antagonists yielded data
      consistent with the presence of multiple subtypes (M(1)/M(2)/M(3)/M(5)) of mAChRs
      in both human atrial (HA) and ventricular (HV) tissues. Expression of mRNAs
      encoding all five subtypes was readily detected by reverse transcription
      polymerase chain reaction in both HA and HV samples. Immunoblotting with subtype
      specific antibodies confirmed the presence of M(1), M(2), M(3), and M(5), but not
      M(4), proteins in membrane preparations from both HA and HV. The protein levels
      of M(1) and M(2) were comparable between HA and HV. Although the density of M(3)
      appeared approximately 10-fold higher in HV than HA, that of M(5) was
      approximately 5 times lower in HV than in HA. Positive immunostaining of single
      ventricular myocytes by M(1), M(2), M(3), and M(5) antibodies, respectively, was
      consistently detected. Under confocal microscopy, M(5) showed characteristic
      localization to the intercalated discs, whereas other subtypes were more evenly
      distributed throughout the surface membrane. Our results provide the first
      molecular evidence for the presence of multiple subtypes of mAChR, including
      endogenous M(5) receptors, in human hearts and suggest that different subtypes
      have different tissue distributions and cellular localization.

PMID- 11306685
TI  - Characterization of glutamate-gated chloride channels in the pharynx of wild-type
      and mutant Caenorhabditis elegans delineates the role of the subunit GluCl-alpha2
      in the function of the native receptor.
AB  - Glutamate-gated chloride (GluCl) channels are the site of action of the
      anthelmintic ivermectin. Previously, the Xenopus laevis oocyte expression system
      has been used to characterize GluCl channels cloned from Caenorhabditis elegans.
      However, information on the native, pharmacologically relevant receptors is
      lacking. Here, we have used a quantitative pharmacological approach and
      intracellular recording techniques of C. elegans pharynx to characterize them.
      The glutamate response was a rapidly desensitizing, reversible, chloride
      dependent depolarization (EC(50) = 166 microM), only weakly antagonized by
      picrotoxin. The order of potency of agonists was ibotenate > L-glutamate >
      kainate = quisqualate. Ivermectin potently and irreversibly depolarized the
      muscle (EC(50) = 2.7 nM). No further depolarization was seen with coapplication
      of maximal glutamate during the maximal ivermectin response, indicating that
      ivermectin depolarizes the muscle by the same ionic mechanism as glutamate (i.e.,
      chloride). The potency of ivermectin on the pharynx was greater than at any of
      the GluCl subunits expressed in X. laevis oocytes. This effect of ivermectin was
      abolished in the mutant avr-15, which lacks a functional GluCl-alpha2 subunit.
      However, a chloride-dependent, nondesensitizing response to glutamate persisted.
      Therefore, the GluCl-alpha2 subunit confers ivermectin sensitivity and a high
      affinity desensitizing glutamate response on the native pharyngeal GluCl
      receptor.

PMID- 11306686
TI  - Antimitogenic actions of organic nitrates are potentiated by sildenafil and
      mediated via activation of protein kinase A.
AB  - Migration and proliferation of vascular smooth muscle cells (SMC) in response to
      platelet-derived growth factor (PDGF) and other mitogens play an important role
      in restenosis after coronary angioplasty. Elevation of both cAMP and cGMP has
      been shown to inhibit SMC mitogenesis. The aim of this study was to examine the
      antimitogenic actions of organic nitrates and sildenafil and to clarify the role
      of cyclic nucleotide-dependent protein kinases (PKA, PKG) in this action. Organic
      nitrates [glycerol trinitrate (GTN), isosorbide 5'-mononitrate (ISMN),
      pentaerythrityl-tetranitrate (PETN)] and the PDE5 inhibitor sildenafil reduced
      PDGF-induced DNA synthesis, measured by ((3)H]thymidine incorporation. GTN, ISMN,
      and PETN acted synergistically with sildenafil (1 microM) on inhibition of PDGF
      induced DNA synthesis, increase of intracellular cyclic nucleotides, and
      vasodilator-stimulated phosphoprotein phosphorylation. The highly selective PKA
      inhibitor PKI abolished these actions of sildenafil and organic nitrates, whereas
      the PKG inhibitors KT5823 and (Rp)-8-pCPT-cGMPS had no effect. In addition,
      selective activation of PKG without inhibition of PDE3 by the cGMP analog 8-pCPT
      cGMP (100 microM) had no antimitogenic effect. The data suggest that 1) organic
      nitrates and sildenafil exert antimitogenic actions by activation of PKA via
      inhibition of PDE3, but not by activation of PKG and 2) that antimitogenic
      effects of organic nitrates are potentiated by sildenafil at therapeutic plasma
      levels.

PMID- 11306687
TI  - Characterization of the dizocilpine binding site on the nicotinic acetylcholine
      receptor.
AB  - Although the dissociative anesthetic dizocilpine [(+)-MK-801] inhibits nicotinic
      acetylcholine receptor (AChR) function in a noncompetitive manner, the location
      of the dizocilpine binding site(s) has yet to be clearly established. Thus, to
      characterize the binding site for dizocilpine on the AChR we examined 1) the
      dissociation constant (K(d)) and stoichiometry of [(3)H]dizocilpine binding; 2)
      the displacement of dizocilpine radioligand binding by noncompetitive inhibitors
      (NCIs) and conversely dizocilpine displacement of fluorescent and radiolabeled
      NCIs from their respective high-affinity binding sites on the AChR; and 3)
      photoaffinity labeling of the AChR using (125)I-dizocilpine. The results
      establish that one high-affinity (K(d) = 4.8 microM) and several (3-6) low
      affinity (K(d) = approximately 140 microM) binding sites exist for dizocilpine on
      the desensitized and resting AChR, respectively. The binding of the fluorescent
      NCIs ethidium, quinacrine, and crystal violet as well as
      [(3)H]thienylcyclohexylpiperidine was inhibited by dizocilpine on desensitized
      AChRs. However, Schild-type analyses indicate that only the inhibition of
      quinacrine in the desensitized state seems to be mediated by a mutually exclusive
      action. Photoaffinity labeling of the AChR by (125)I-dizocilpine was primarily
      restricted to the alpha1 subunit and subsequent mapping revealed that the
      principal sites of labeling are localized to the M4 (approximately 70%) and M1
      (30%) transmembrane domains. Collectively, the data indicate that the high
      affinity dizocilpine binding site is not located in the lumen of the ion channel
      but probably near the quinacrine binding locus at a nonluminal domain in the AChR
      desensitized state.

PMID- 11306688
TI  - Direct activation of an inwardly rectifying potassium channel by arachidonic
      acid.
AB  - Arachidonic acid (AA) is an important constituent of membrane phospholipids and
      can be liberated by activation of cellular phospholipases. AA modulates a variety
      of ion channels via diverse mechanisms, including both direct effects by AA
      itself and indirect actions through AA metabolites. Here, we report excitatory
      effects of AA on a cloned human inwardly rectifying K(+) channel, Kir2.3, which
      is highly expressed in the brain and heart and is critical in regulating cell
      excitability. AA potently and reversibly increased Kir2.3 current amplitudes in
      whole-cell and excised macro-patch recordings (maximal whole-cell response to AA
      was 258 +/- 21% of control, with an EC(50) value of 447 nM at -97 mV). This
      effect was apparently caused by an action of AA at an extracellular site and was
      not prevented by inhibitors of protein kinase C, free oxygen radicals, or AA
      metabolic pathways. Fatty acids that are not substrates for metabolism also
      potentiated Kir2.3 current. AA had no effect on the currents flowing through
      Kir2.1, Kir2.2, or Kir2.4 channels. Experiments with Kir2.1/2.3 chimeras
      suggested that, although AA may bind to both Kir2.1 and Kir2.3, the transmembrane
      and/or intracellular domains of Kir2.3 were essential for channel potentiation.
      These results argue for a direct mechanism of AA modulation of Kir2.3.

PMID- 11306689
TI  - Cocaine blocks HERG, but not KvLQT1+minK, potassium channels.
AB  - Cocaine causes cardiac arrhythmias, sudden death, and occasionally long QT
      syndrome in humans. We investigated the effect of cocaine on the human K(+)
      channels HERG and KvLQT1+minK that encode native rapidly (I(Kr)) and slowly
      (I(Ks)) activating delayed rectifier K(+) channels in the heart. HERG and
      KvLQT1+minK channels were heterologously expressed in human embryonic kidney 293
      cells, and whole-cell currents were recorded. Cocaine had no effect on
      KvLQT1+minK current in concentrations up to 200 microM. In contrast, cocaine
      reversibly blocked HERG current with half-maximal block of peak tail current of
      7.2 microM. By using a protocol to quickly activate HERG channels, we found that
      cocaine block developed rapidly after channel activation. At 0 mV, the time
      constants for the development of block were 38.2 +/- 2.1, 15.2 +/- 0.8, and 6.9
      +/- 1.1 ms in 10, 50 and 200 microM cocaine, respectively. Cocaine-blocked
      channels also recovered rapidly from block after repolarization. At -100 mV,
      recovery from block followed a biphasic time course with fast and slow time
      constants of 3.5 +/- 0.7 and 100.3 +/- 15.4 ms, respectively. Using N-methyl
      cocaine, a permanently charged, membrane-impermeable cocaine analog, block of
      HERG channels rapidly developed when the drug was applied intracellularly through
      the patch pipette, suggesting that the cocaine binding site on the HERG protein
      is located on a cytoplasmic accessible domain. These results indicate that
      cocaine suppresses HERG, but not KvLQT1+minK, channels by preferentially blocking
      activated channels, that it unblocks upon repolarization, and does so with unique
      ultrarapid kinetics. Because the cocaine concentration range we studied is
      achieved in humans, HERG block may provide an additional mechanism for cocaine
      induced arrhythmias and sudden death.

PMID- 11306690
TI  - Charged amino acids in the transmembrane domains are involved in the
      determination of the substrate specificity of rat Mrp2.
AB  - Multidrug resistance-associated protein 2 (MRP2) transports glutathione
      conjugates, glucuronide conjugates, and sulfated conjugates of bile acids. In the
      present study, we examined the role of charged amino acids in the transmembrane
      domains of rat Mrp2, conserved among MRP families, using the isolated membrane
      vesicles from Sf9 cells infected with the recombinant baculoviruses. By
      normalizing the transport activity for compounds by that for estradiol 17beta-D
      glucuronide (E(2)17betaG), it was indicated that the site-directed mutagenesis
      from Lys to Met at 325 (K325M) and from Arg to Leu at 586 (R586L) results in a
      marked reduction in the transport for glutathione conjugates [2,4-dinitrophenyl-S
      glutathione (DNP-SG) and leukotriene (LT) C(4)] without affecting that for 6
      hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridymethyl) benzothiazole glucuronide
      and taurolithocholate sulfate. In contrast to the reduced affinity for DNP-SG,
      the affinity for E(2)17betaG was increased severalfold in these mutant Mrp2s,
      suggesting the amino acids at 325 and 586 play an important role in
      distinguishing between glutathione and glucuronide conjugates. The comparable
      affinity for LTD(4), LTE(4), and LTF(4) in these mutant Mrp2s with that in wild
      type Mrp2 indicates that recognition of LTC(4) metabolites by Mrp2 is different
      from that of LTC(4). The transport activity for glutathione conjugate was
      retained on R586K, whereas no such complementary cationic amino acid effect was
      observed in K325R. In addition, R1206M and E1208Q exhibited the loss of transport
      activity for the tested compounds. The results of the present study demonstrate
      that the charged amino acids in the transmembrane domain of rat Mrp2 may play an
      important role in the recognition and/or transport of its substrates.

PMID- 11306691
TI  - Phospholipids as modulators of K(ATP) channels: distinct mechanisms for control
      of sensitivity to sulphonylureas, K(+) channel openers, and ATP.
AB  - Recent work has established membrane phospholipids such as phosphatidylinositol
      4,5-bisphosphate (PIP(2)) as potent regulators of K(ATP) channels controlling
      open probability and ATP sensitivity. We here investigated the effects of
      phospholipids on the pharmacological properties of cardiac type K(ATP)
      (Kir6.2/SUR2A) channels. In excised membrane patches K(ATP) channels showed
      considerable variability in sensitivity to glibenclamide and ATP. Application of
      the phosphatidylinositol phosphates (PIPs) phosphatidylinositiol-4-phosphate,
      PIP(2), and phosphatidylinositol-3,4,5-trisphosphate reduced sensitivity to ATP
      and glibenclamide closely resembling the native variability. Insertion of the
      patch back into the oocyte (patch-cramming) restored high ATP and glibenclamide
      sensitivity, indicating reversible modulation of K(ATP) channels via endogenous
      PIPs-degrading enzymes. Thus, the observed variability seemed to result from
      differences in the membrane phospholipid content. PIP(2) also diminished
      activation of K(ATP) channels by the K(+) channel openers (KCOs) cromakalim and
      P1075. The properties mediated by the sulphonylurea receptor (sensitivity to
      sulfonylureas and KCOs) seemed to be modulated by PIPs via a different mechanism
      than ATP inhibition mediated by the Kir6.2 subunits. First, polycations abolished
      the effect of PIP(2) on ATP inhibition consistent with an electrostatic mechanism
      but only weakly affected glibenclamide inhibition and activation by KCOs. Second,
      PIP(2) had clearly distinct effects on the concentration-response curves for ATP
      and glibenclamide. However, PIPs seemed to mediate the different effects via the
      Kir6.2 subunits because a mutation in Kir6.2 (R176A) attenuated simultaneously
      the effects of PIP(2) on ATP and glibenclamide inhibition. Finally, experiments
      with various lipids revealed structural features necessary to modulate K(ATP)
      channel properties and an artificial lipid (dioleoylglycerol-succinyl
      nitriloacetic acid) that mimicked the effects of PIPs on K(ATP) channels.

PMID- 11306692
TI  - The novel triterpenoid CDDO induces apoptosis and differentiation of human
      osteosarcoma cells by a caspase-8 dependent mechanism.
AB  - The oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is
      a multifunctional molecule that induces monocytic differentiation of human
      myeloid leukemia cells and inhibits proliferation of diverse human tumor cell
      lines. The present studies on human osteosarcoma cells demonstrate that CDDO
      induces mitochondrial cytochrome c release, caspase-3 activation, and
      internucleosomal DNA fragmentation. Overexpression of the caspase-8 inhibitor
      CrmA blocked CDDO-induced cytochrome c release and apoptosis. By contrast,
      overexpression of the antiapoptotic Bcl-x(L) protein blocked CDDO-induced
      cytochrome c release, but only partly inhibited caspase-3 activation and
      apoptosis. In concert with these findings, we demonstrate that CDDO: 1) activates
      caspase-8 and thereby caspase-3 by a cytochrome c-independent mechanism and 2)
      induces cytochrome c release by caspase-8-dependent cleavage of Bid. The results
      also demonstrate that treatment of osteosarcoma cells with CDDO induces
      differentiation, as assessed by alkaline phosphatase activity and osteocalcin
      production, and that this response is abrogated in cells that overexpress CrmA.
      These findings demonstrate that CDDO induces both osteoblastic differentiation
      and apoptosis by caspase-8-dependent mechanisms.

PMID- 11306693
TI  - Disparate role of Na(+) channel D2-S6 residues in batrachotoxin and local
      anesthetic action.
AB  - Batrachotoxin (BTX) stabilizes the voltage-gated Na(+) channels in their open
      conformation, whereas local anesthetics (LAs) block Na(+) conductance. Site
      directed mutagenesis has identified clusters of common residues at D1-S6, D3-S6,
      and D4-S6 segments within the alpha-subunit Na(+) channel that are critical for
      binding of these two types of ligands. In this report, we address whether segment
      D2-S6 is similarly involved in both BTX and LA actions. Thirteen amino acid
      positions from G783 to L795 of the rat skeletal muscle Na(+) channel ((mu)1/Skm1)
      were individually substituted with a lysine residue. Four mutants (N784K, L785K,
      V787K, and L788K) expressed sufficient Na(+) currents for further studies.
      Activation and/or inactivation gating was altered in mutant channels; in
      particular, mu1-V787K displays enhanced slow inactivation and exhibited use
      dependent inhibition of peak Na(+) currents during repetitive pulses. Two of
      these four mutants, (mu)1-N784K and (mu)1-L788K, were completely resistant to 5
      microM BTX. This BTX-resistant phenotype could be caused by structural
      perturbations induced by a lysine point mutation in the D2-S6 segment. However,
      these two BTX-resistant mutants remained quite sensitive to bupivacaine block
      with affinity for inactivated Na(+) channels (K(I)) of approximately 10 microM or
      less, which suggests that (mu)1-N784 and (mu)1-L788 residues are not in close
      proximity to the LA binding site.

PMID- 11306694
TI  - Effect of alpha subunit on allosteric modulation of ion channel function in
      stably expressed human recombinant gamma-aminobutyric acid(A) receptors
      determined using (36)Cl ion flux.
AB  - Inhibitory gamma-aminobutyric acid (GABA)(A) receptors are subject to modulation
      at a variety of allosteric sites, with pharmacology dependent on receptor subunit
      combination. The influence of different alpha subunits in combination with
      beta3gamma2s was examined in stably expressed human recombinant GABA(A) receptors
      by measuring (36)Cl influx through the ion channel pore. Muscimol and GABA
      exhibited similar maximal efficacy at each receptor subtype, although muscimol
      was more potent, with responses blocked by picrotoxin and bicuculline. Receptors
      containing the alpha3 subunit exhibited slightly lower potency. The comparative
      pharmacology of a range of benzodiazepine site ligands was examined, revealing a
      range of intrinsic efficacies at different receptor subtypes. Of the diazepam
      sensitive GABA(A) receptors (alpha1, alpha2, alpha3, alpha5), alpha5 showed the
      most divergence, being discriminated by zolpidem in terms of very low affinity,
      and CL218,872 and CGS9895 with different efficacies. Benzodiazepine potentiation
      at alpha3beta3gamma2s with nonselective agonist chlordiazepoxide was greater than
      at alpha1, alpha2, or alpha5 (P < 0.001). The presence of an alpha4 subunit
      conferred a unique pharmacological profile. The partial agonist bretazenil was
      the most efficacious benzodiazepine, despite lower alpha4 affinity, and FG8205
      displayed similar efficacy. Most striking were the lack of affinity/efficacy for
      classical benzodiazepines and the relatively high efficacy of Ro15-1788 (53 +/-
      12%), CGS8216 (56 +/- 6%), CGS9895 (65 +/- 6%), and the weak partial inverse
      agonist Ro15-4513 (87 +/- 5%). Each receptor subtype was modulated by
      pentobarbital, loreclezole, and 5alpha-pregnan-3alpha-ol-20-one, but the type of
      alpha subunit influenced the level of potentiation. The maximal pentobarbital
      response was significantly greater at alpha4beta3gamma2s (226 +/- 10% increase in
      the EC(20) response to GABA) than any other modulator. The rank order of
      potentiation for pregnanolone was alpha5 > alpha2 > alpha3 = alpha4 > alpha1, for
      loreclezole alpha1 = alpha2 = alpha3 > alpha5 > alpha4, and for pentobarbital
      alpha4 = alpha5 = alpha2 > alpha1 = alpha3.

PMID- 11306695
TI  - High-intensity p38 kinase activity is critical for p21(cip1) induction and the
      antiproliferative function of G(i) protein-coupled receptors.
AB  - G protein-coupled receptors can stimulate the p38 kinase cascade, but the effect
      this has on cell growth remains poorly characterized. Here we show human
      somatostatin sst(2) and sst(4) receptors inhibit basic fibroblast growth factor
      (bFGF)-induced proliferation, via a mechanism that was blocked by the p38
      inhibitor PD 169316. The sst(4) receptor could also induce a proliferative
      activity in the absence of bFGF, which was unaffected by PD 169316. In contrast,
      the sst(3) receptor had no effect on basal cell growth or on the proliferation
      evoked by bFGF. The extracellular signal-regulated kinase activity stimulated by
      the sst(3) receptor was transient in duration compared with a sustained activity
      induced by the sst(2) and sst(4) receptors and which was critical for the
      proliferative response of the latter receptor. In addition, activated sst(2) and
      sst(4) but not sst(3) receptors evoked a prolonged phosphorylation of p38 that
      was amplified by bFGF. The accumulation of the cell cycle inhibitor p21(cip1) was
      only apparent after sst(2) and sst(4) receptor activation in the presence of
      bFGF, which was sensitive to PD 169316 or pertussis toxin. Thus, the contrasting
      antiproliferative effects evoked by the human sst(2), sst(3), and sst(4)
      receptors can be accounted for by their differential abilities to activate p38.
      This activity is critical for p21(cip1) induction, blockade of entry into S
      phase, as indicated by the lack of retinoblastoma protein phosphorylation, and
      the associated antiproliferative activity of somatostatin. Furthermore, by
      changing the intracellular signaling threshold of p38 through cooperative effects
      of somatostatin and bFGF, the sst(4) receptor can mediate opposing effects on
      cell proliferation.

PMID- 11306696
TI  - Quantitative analysis of inward and outward transport rates in cells stably
      expressing the cloned human serotonin transporter: inconsistencies with the
      hypothesis of facilitated exchange diffusion.
AB  - Quantitative aspects of inward and outward transport of substrates by the human
      plasmalemmal serotonin transporter (hSERT) were investigated. Uptake and
      superfusion experiments were performed on human embryonic kidney 293 cells
      permanently expressing the hSERT using [(3)H]serotonin (5-HT) and [(3)H]1-methyl
      4-phenylpyridinium (MPP(+)) as substrates. Saturation analyses rendered K(m)
      values of 0.60 and 17.0 microM for the uptake of [(3)H]5-HT and [(3)H]MPP(+),
      respectively. Kinetic analysis of outward transport was performed by prelabeling
      the cells with increasing concentrations of the two substrates and exposing them
      to a saturating concentration of p-chloroamphetamine (PCA; 10 microM). Apparent
      K(m) values for PCA induced transport were 564 microM and about 7 mM
      intracellular [(3)H]5-HT and [(3)H]MPP(+), respectively. Lowering the
      extracellular Na(+) concentrations in uptake and superfusion experiments revealed
      differential effects on substrate transport: at 10 mM Na(+) the K(m) value for
      [(3)H]5-HT uptake increased approximately 5-fold and the V(max) value remained
      unchanged. The K(m) value for [(3)H]MPP(+) uptake also increased, but the V(max)
      value was reduced by 50%. When efflux was studied at saturating prelabeling
      conditions of both substrates, PCA as well as unlabeled 5-HT and MPP(+) (all
      substances at saturating concentrations) induced the same efflux at 10 mM and 120
      mM Na(+). Thus, notwithstanding a 50% reduction in the V(max) value of transport
      into the cell, MPP(+) was still able to induce maximal outward transport of
      either substrate. Thus, hSERT-mediated inward and outward transport seems to be
      independently modulated and may indicate inconsistencies with the classical model
      of facilitated exchange diffusion.

PMID- 11306697
TI  - PI3K inhibitors reverse the suppressive actions of insulin on CYP2E1 expression
      by activating stress-response pathways in primary rat hepatocytes.
AB  - Insulin-associated signaling pathways are critical in the regulation of hepatic
      physiology. Recent inhibitor-based studies have implicated a mechanistic role for
      phosphatidylinositol 3' kinase (PI3K) in the insulin-mediated suppression of
      CYP2E1 mRNA levels in hepatocytes. We investigated the dose dependence for this
      response and for the effects of insulin and extracellular matrix on PI3K
      signaling and CYP2E1 mRNA expression levels using a highly defined rat primary
      hepatocyte culture system. The PI3K inhibitors wortmannin and LY294002 stimulated
      stress-activated protein kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK) and p38
      mitogen-activated protein kinase (MAPK) phosphorylation in a rapid and
      concentration-dependent manner that paralleled the inhibition of protein kinase B
      (PKB) phosphorylation. Although PI3K inhibitors reversed the suppressive effects
      of insulin on CYP2E1 expression, these effects only occurred at concentrations
      well in excess of those required to achieve complete inhibition of PKB
      phosphorylation. These same concentrations produced cytotoxic responses as
      evidenced by perturbed cellular morphology and elevated release of lactate
      dehydrogenase. Wortmannin-mediated activation of the SAPK/JNK and p38 MAPK
      pathways also resulted in the mobilization of activator protein-1 complex to the
      nuclear compartment. We conclude that the suppression of CYP2E1 mRNA expression
      by insulin is not directly associated with PI3K-dependent pathway activation, but
      rather is linked to a cytotoxic response stemming from acute challenge with PI3K
      inhibitors.

PMID- 11306698
TI  - Activation of phosphatidylinositol 3-kinase and Akt by tert-butylhydroquinone is
      responsible for antioxidant response element-mediated rGSTA2 induction in H4IIE
      cells.
AB  - The protective adaptive response to electrophiles and reactive oxygen species is
      mediated by enhanced expression of phase II detoxifying genes, including
      glutathione S-transferases, through activation of antioxidant response element
      (ARE). The current study was designed to investigate the role of
      phosphatidylinositol 3-kinase (PI3-kinase)-Akt and mitogen-activated protein
      (MAP) kinase signaling pathways in the induction of rGSTA2 by tert
      butylhydroquinone (t-BHQ). Nuclear ARE complex was activated 1 to 6 h after
      treatment of H4IIE cells with t-BHQ. The rGSTA2 mRNA level was elevated 6 to 24 h
      after t-BHQ treatment, which led to the enzyme induction. Activities of PI3
      kinase and Akt were increased 10 min through 6 h after t-BHQ treatment, whereas
      wortmannin or LY294002, PI3-kinase inhibitors, completely abolished ARE binding
      activity and increases in rGSTA2 mRNA and protein. Extracellular signal-regulated
      kinase (ERK), p38 MAP kinase, and c-Jun N-terminal kinase (JNK) were all
      activated by t-BHQ. Treatment with PD98059, an ERK inhibitor, however, increased
      rGSTA2 mRNA and further enhanced t-BHQ-induced expression of rGSTA2. Neither
      SB203580 nor overexpression of JNK1 dominant negative mutant altered t-BHQ
      inducible rGSTA2 expression. These results demonstrated that t-BHQ activated PI3
      kinase and Akt, which was responsible for ARE-mediated rGSTA2 induction, and that
      ERK might negatively regulate rGSTA2 expression, whereas activation of p38 MAP
      kinase or of JNK by t-BHQ was not associated with the enzyme induction.

PMID- 11306699
TI  - Dual incorporation of photoaffinity ligands on dopamine transporters implicates
      proximity of labeled domains.
AB  - We have recently developed novel high-affinity blockers for the dopamine
      transporter (DAT) by carrying out structure-activity studies of GBR 12909
      molecule piperidine analogs. To investigate the molecular basis of binding of
      these compounds in comparison to known sites of action of GBR 12909, cocaine, and
      benztropine analogs, we developed a piperidine-based photoaffinity label
      [(125)I]4-[2-(diphenylmethoxy)ethyl]-1-[(4-azido- 3-iodophenyl)methyl]-piperidine
      [(125)I]AD-96-129), and used proteolysis and epitope-specific immunoprecipitation
      to identify the protein domains that interact with the ligand. [(125)I]AD-96-129
      became incorporated into two different regions of the DAT primary sequence, an N
      terminal site containing transmembrane domains (TMs) 1 to 2, and a second site
      containing TMs 4 to 6. Both of these regions have been identified previously as
      sites involved in the binding of other DAT photoaffinity labels. However, in
      contrast to the previously characterized ligands that showed nearly complete
      specificity in their binding site incorporation, [(125)I]AD-96-129 became
      incorporated into both sites at comparable levels. These results suggest that the
      two domains may be in close three-dimensional proximity and contribute to binding
      of multiple uptake blockers. We also found that DATs labeled with [(125)I]AD-96
      129 or other photoaffinity labels displayed distinctive sensitivities to
      proteolysis of a site in the second extracellular loop, with protease resistance
      related to the extent of ligand incorporation in the TM4 to 6 region. These
      differences in protease sensitivity may indicate the relative proximity of the
      ligands to the protease site or reflect antagonist-induced conformational changes
      in the loop related to transport inhibition.

PMID- 11306700
TI  - Involvement of nuclear factor kappaB in c-Myc induction by tubulin polymerization
      inhibitors.
AB  - We showed previously that microtubule disassembly by vinblastine induces the
      proto-oncogene c-myc in epithelial mammary HBL100 cells. In this study, we
      demonstrate that vinblastine treatment in these cells, in contrast to what was
      observed with the colon adenocarcinoma cell line HT29-D4, activated the
      transcription factor NFkappaB, which has been involved in c-myc regulation. The
      microtubule disassembly also induced IkappaB degradation. Using transient
      transfection analysis, we show that the trans-activation of c-myc by vinblastine
      was decreased when NFkappaB binding sites on c-myc promoter were mutated.
      Additionally, we demonstrate that microtubule dissolution trans-activated a
      thymidine kinase-CAT construct containing an NFkappaB binding site at -1180 to 
      1080 bp relative to the P1 promoter. Thus, vinblastine up-regulates the enhancer
      activity of the NFkappaB binding site. These results suggest that microtubule
      disassembly induced by vinblastine can trans-activate the c-myc oncogene through
      NFkappaB. Taking into consideration the paradoxical roles of both c-myc and
      NFkappaB in proliferation or apoptosis, this data reveals the complex action
      mechanism of this microtubule interfering agent.

PMID- 11306701
TI  - Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and atpase
      activities by interaction with dietary flavonoids.
AB  - The 190-kDa phosphoglycoprotein multidrug resistance protein 1 (MRP1) (ABCC1)
      confers resistance to a broad spectrum of anticancer drugs and also actively
      transports certain xenobiotics with reduced glutathione (GSH) (cotransport) as
      well as conjugated organic anions such as leukotriene C(4) (LTC(4)). In the
      present study, we have investigated a series of bioflavonoids for their ability
      to influence different aspects of MRP1 function. Most flavonoids inhibited MRP1
      mediated LTC(4) transport in membrane vesicles and inhibition by several
      flavonoids was enhanced by GSH. Five of the flavonoids were competitive
      inhibitors of LTC(4) transport (K(i), 2.4-21 microM) in the following rank order
      of potency: kaempferol > apigenin (+ GSH) > quercetin > myricetin > naringenin (+
      GSH). These flavonoids were less effective inhibitors of 17beta-estradiol 17beta
      (D-glucuronide) transport. Moreover, their rank order of inhibitory potency for
      this substrate differed from that for LTC(4) transport inhibition but correlated
      with their relative lipophilicity. Several flavonoids, especially naringenin and
      apigenin, markedly stimulated GSH transport by MRP1, suggesting they may be
      cotransported with this tripeptide. Quercetin inhibited the ATPase activity of
      purified reconstituted MRP1 but stimulated vanadate-induced trapping of 8-azido
      alpha-[(32)P]ADP by MRP1. In contrast, kaempferol and naringenin stimulated both
      MRP1 ATPase activity and trapping of ADP. In intact MRP1-overexpressing cells,
      quercetin reduced vincristine resistance from 8.9- to 2.2-fold, whereas
      kaempferol and naringenin had no effect. We conclude that dietary flavonoids may
      modulate the organic anion and GSH transport, ATPase, and/or drug resistance
      conferring properties of MRP1. However, the activity profile of the flavonoids
      tested differed from one another, suggesting that at least some of these
      compounds may interact with different sites on the MRP1 molecule.

PMID- 11306702
TI  - Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine
      cytidine kinases.
AB  - Uridine-cytidine kinases (UCK) have important roles for the phosphorylation of
      nucleoside analogs that are being investigated for possible use in chemotherapy
      of cancer. We have cloned the cDNA of two human UCKs. The approximately 30-kDa
      proteins, named UCK1 and UCK2, were expressed in Escherichia coli and shown to
      catalyze the phosphorylation of Urd and Cyd. The enzymes did not phosphorylate
      deoxyribonucleosides or purine ribonucleosides. UCK1 mRNA was detected as two
      isoforms of approximately 1.8 and approximately 2.7 kb. The 2.7-kb band was
      ubiquitously expressed in the investigated tissues. The band of approximately 1.8
      kb was present in skeletal muscle, heart, liver, and kidney. The two isoforms of
      UCK2 mRNA of 1.2 and 2.0 kb were only detected in placenta among the investigated
      tissues. The genes encoding UCK1 and UCK2 were mapped to chromosome 9q34.2-9q34.3
      and 1q22-1q23.2, respectively. We tested 28 cytidine and uridine nucleoside
      analogs as possible substrates of the enzymes. The enzymes phosphorylated several
      of the analogs, such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5
      bromouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, 5-fluorocytidine, 2
      thiocytidine, 5-methylcytidine, and N(4)-anisoylcytidine. The cloning and
      recombinant expression of the two human UCKs will be important for development of
      novel pyrimidine ribonucleoside analogs and the characterization of their
      pharmacological activation.

PMID- 11306703
TI  - Determination of amino acid residues that are accessible from the ligand binding
      crevice in the seventh transmembrane-spanning region of the human A(1) adenosine
      receptor.
AB  - The substituted-cysteine accessibility method (SCAM) was applied to transmembrane
      span seven of the human A(1) adenosine receptor (hA(1)AR) to reveal a subset of
      amino acids that are exposed to the ligand-binding crevice. The SCAM approach
      involved a systematic probe of receptor structure by individual substitutions of
      residues K265 (7.30) to R296 (7.61) with cysteine. In most cases, hA(1)AR
      substituted-cysteine mutant membranes displayed antagonist dissociation binding
      constants that did not differ significantly from wild-type (WT). Radioligand
      binding assays were used to compare cell membranes that were treated with
      hydrophilic, sulfhydryl-specific methanethiosulfonate derivatives with control
      cell membranes. Position H278 was previously reported to be required for A(1)AR
      ligand binding; however, that report did not establish that H278 represents a
      contact point for ligands. Cysteine-substitution at H278 yields membrane
      preparations with greatly decreased receptor density compared with WT membranes
      from cells in the same transfection experiment. However, H278C membranes retain a
      measurable fraction of antagonist binding. This observation allows for the
      investigation of binding-crevice accessibility at position 278 and suggests that
      H278 may not be required for binding of antagonist ligands. Our data reveal the
      binding-crevice accessibility of residues T270 (7.35), A273 (7.38), I274 (7.39),
      T277 (7.42), H278 (7.43), N284 (7.49), and Y288 (7.53) in the hA(1)AR. These data
      are consistent with the high-resolution structure of bovine rhodopsin that
      features three alpha-helical turns in this region that are interrupted by an
      elongated, nonhelical structure from positions 7.43 to 7.48 in the primary amino
      acid sequence.

PMID- 11306704
TI  - Tripterygium wilfordii Hook F extract suppresses proinflammatory cytokine-induced
      expression of matrix metalloproteinase genes in articular chondrocytes by
      inhibiting activating protein-1 and nuclear factor-kappaB activities.
AB  - The major pathologic manifestations of rheumatoid arthritis (RA) and
      osteoarthritis (OA) are joint inflammation and articular cartilage resorption by
      proinflammatory cytokine-stimulated matrix metalloproteinases (MMPs) and
      aggrecanases. The Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) is
      effective for treatment of various types of arthritis. However, mechanisms and
      targets of its actions are poorly understood. Anti-inflammatory activities of the
      extracts of this plant were previously attributed to inhibition of cyclooxygenase
      2 mRNA and prostaglandin E(2) synthesis. Here, we show that in primary human
      femoral head osteoarthritic and normal bovine chondrocytes, TWHF partially or
      completely inhibited mRNA and protein expression of tumor necrosis factor-alpha,
      interleukin (IL)-1, and IL-17-inducible MMP-3 and MMP-13. This agent also
      inhibited cytokine-stimulated MMP-3 protein expression in human synovial
      fibroblasts. A dose range of 2.5 to 10 ng/ml of TWHF was effectively inhibitory
      for IL-1. Pretreatment for 30 min or 1 h (but not 2-10 h) after IL-1 treatment
      with TWHF inhibited MMP-3 RNA induction. The inhibitory doses had no adverse
      effect on the viability of chondrocytes. Mechanistic studies revealed no impact
      on the activation of extracellular signal-regulated kinase, p38, and c-Jun N
      terminal kinase mitogen-activated protein kinases. Instead, TWHF partially
      inhibited DNA binding capacity of cytokine-stimulated activating protein-1 (AP-1)
      and nuclear factor-kappaB (NF-kappaB) transcription factors. Therefore, besides
      its anti-inflammatory activity, this agent may also be effective in blocking
      cartilage matrix resorption by MMPs by impairing AP-1 and NF-kappaB binding
      activities. Thus, TWHF extract contains novel inhibitors of MMP expression that
      may be of therapeutic potential in arthritis and other conditions associated with
      increased MMPs.

PMID- 11306705
TI  - Structural determinants of adenophostin A activity at inositol trisphosphate
      receptors.
AB  - Adenophostin A is the most potent known agonist of inositol 1,4,5-trisphosphate
      (InsP(3)) receptors. Ca(2+) release from permeabilized hepatocytes was 9.9 +/-
      1.6-fold more sensitive to adenophostin A (EC(50), 14.7 +/- 2.4 nM) than to
      InsP(3) (145 +/- 10 nM), consistent with the greater affinity of adenophostin A
      for hepatic InsP(3) receptors (K(d) = 0.48 +/- 0.06 and 3.09 +/- 0.33 nM,
      respectively). Here, we systematically modify the structures of the glucose,
      ribose, and adenine moieties of adenophostin A and use Ca(2+) release and binding
      assays to define their contributions to high-affinity binding. Progressive
      trimming of the adenine of adenophostin A reduced potency, but it fell below that
      of InsP(3) only after complete removal of the adenine. Even after substantial
      modifications of the adenine (to uracil or even unrelated aromatic rings,
      retaining the beta-orientation), the analogs were more potent than InsP(3). The
      only analog with an alpha-ribosyl linkage had massively decreased potency. The 2'
      phosphate on the ribose ring of adenophostin A was essential and optimally active
      when present on a five-membered ring in a position stereochemically equivalent to
      its location in adenophostin A. Xylo-adenophostin, where xylose replaces the
      glucose ring of adenophostin A, was only slightly less potent than adenophostin
      A, whereas manno-adenophostin (mannose replacing glucose) had similar potency to
      InsP(3). These results are consistent with the relatively minor role of the 3
      hydroxyl of InsP(3) (the equivalent is absent from xylo-adenophostin) and greater
      role of the equatorial 6-hydroxyl (the equivalent is axial in manno
      adenophostin). This is the first comprehensive analysis of all the key structural
      elements of adenophostin A, and it provides a working model for the design of
      related high-affinity ligands of InsP(3) receptors.

PMID- 11306706
TI  - Mitogen-activated protein kinase kinase inhibitor PD98059 blocks the trans
      activation but not the stabilization or DNA binding ability of hypoxia-inducible
      factor-1alpha.
AB  - Under low oxygen tension, cells increase the transcription of specific genes that
      are involved in angiogenesis, erythropoiesis, and glycolysis. Hypoxia-induced
      gene expression primarily depends on the stabilization of the alpha-subunit of
      hypoxia-inducible factor-1 (HIF-1alpha), which acts as a heterodimeric trans
      activator. Our results indicate that stabilization of HIF-1alpha protein by
      treatment of proteasome inhibitors, is not sufficient for hypoxia-induced gene
      activation, and an additional hypoxia-dependent modification is necessary for
      gene expression by HIF-1alpha. Here, we demonstrate that mitogen-activated
      protein kinase kinase-1 (MEK-1) inhibitor PD98059 does not change either the
      stabilization or DNA binding ability of HIF-1alpha but it inhibits the trans
      activation ability of HIF-1alpha, thereby it reduces the hypoxia-induced
      transcription of both an endogenous target gene and a hypoxia-responsive reporter
      gene. We found that hypoxia induced p42/p44 mitogen-activated protein kinases
      (MAPKs) that are target protein kinases of MEK-1, and that expression of dominant
      negative p42 and p44 MAPK mutants reduced HIF-1-dependent transcription of the
      hypoxia-responsive reporter gene. Our results are the first to identify that
      hypoxia-induced trans-activation ability of HIF-1alpha is regulated by different
      mechanisms than its stabilization and DNA binding, and that these processes can
      be experimentally dissociated. MEK-1/p42/p44 MAPK regulates the trans-activation,
      but not the stabilization or DNA binding ability, of HIF-1alpha.

PMID- 11306707
TI  - Cloning and characterization of the mouse alpha1C/A-adrenergic receptor gene and
      analysis of an alpha1C promoter in cardiac myocytes: role of an MCAT element that
      binds transcriptional enhancer factor-1 (TEF-1).
AB  - alpha1-Adrenergic receptor (AR) subtypes in the heart are expressed by myocytes
      but not by fibroblasts, a feature that distinguishes alpha1-ARs from beta-ARs.
      Here we studied myocyte-specific expression of alpha1-ARs, focusing on the
      subtype alpha1C (also called alpha1A), a subtype implicated in cardiac
      hypertrophic signaling in rat models. We first cloned the mouse alpha1C-AR gene,
      which consisted of two exons with an 18 kb intron, similar to the alpha1B-AR
      gene. The receptor coding sequence was >90% homologous to that of rat and human.
      alpha1C-AR transcription in mouse heart was initiated from a single Inr consensus
      sequence at -588 from the ATG; this and a putative polyadenylation sequence 8.5
      kb 3' could account for the predominant 11 kb alpha1C mRNA in mouse heart. A 5'
      nontranscribed fragment of 4.4 kb was active as a promoter in cardiac myocytes
      but not in fibroblasts. Promoter activity in myocytes required a single muscle
      CAT (MCAT) element, and this MCAT bound in vitro to recombinant and endogenous
      transcriptional enhancer factor-1. Thus, alpha1C-AR transcription in cardiac
      myocytes shares MCAT dependence with other cardiac-specific genes, including the
      alpha- and beta-myosin heavy chains, skeletal alpha-actin, and brain natriuretic
      peptide. However, the mouse alpha1C gene was not transcribed in the neonatal
      heart and was not activated by alpha1-AR and other hypertrophic agonists in rat
      myocytes, and thus differed from other MCAT-dependent genes and the rat alpha1C
      gene.

PMID- 11306708
TI  - Use of antisense oligonucleotides to verify the role of the alpha(1A)-adrenergic
      receptor in the contractility of the rat uterus post partum.
AB  - The adrenergic system plays a major role in the regulation of the contractility
      of the uterus during pregnancy. This study investigated the role of the alpha(1A)
      adrenergic receptor (AR) in this regulation. The use of partial phosphorothioate
      antisense oligodeoxynucleotides (AONs) permitted the sequence-selective
      inhibition of AR gene expression. AONs were injected together with a cationic
      liposomal carrier agent into the post partum rat uterus. Incubation for 12 or 24
      h with the most effective AON (480-AON) caused a 58.7 or 53.0% inhibition,
      respectively, of the expression of the alpha(1A)-AR density, whereas incubation
      for 36 or 48 h resulted in only a 38.8 or 26.7% inhibition, respectively. The
      decrease of the alpha(1A)-AR density by 480-AON was demonstrated by Western blot
      analysis and a radioreceptor binding assay on rat uterus preparations 24 h after
      delivery. The changes in the contractility of the uterus after AON treatment were
      measured on isolated rat uterine tissue by electric field stimulation. The
      significant decrease in the ability of the uterus to contract was indicated by
      the area under the curve method. The electric field studies revealed that the
      specific alpha(1A)-blockers 5-methylurapidil and WB 4101 inhibited the rhythmic
      contraction by about 74 and 70% in the control uteri and by 25 and 20% in 480-AON
      treated uteri, respectively. The curves for the beta-mimetic (terbutaline) and
      alpha(1D)-antagonist (BMY7370) inhibitors were unchanged after 480-AON treatment
      of the uteri. These results suggest the importance of the alpha(1A)-AR in the
      tocolytic effect exerted by the alpha(1)-antagonist, although high concentrations
      of antagonists can not exclude the role of alpha(1D)-ARs, too. Additionally,
      these prove that the knockdown transformation by AONs offers a useful animal
      model for the investigation of receptors controlling the function of uterine
      tissue.

PMID- 11306709
TI  - Calcium channel alpha(2)delta subunits-structure and Gabapentin binding.
AB  - High-voltage activated calcium channels are modulated by a series of auxiliary
      proteins, including those of the alpha(2)delta family. Until recently, only a
      single alpha(2)delta subunit was known, but two further members, alpha(2)delta-2
      and -3, have since been identified. In this study, the structure of these two
      novel subunits has been characterized and binding of the antiepileptic drug
      gabapentin investigated. Using antibodies directed against the amino terminal
      portion of the proteins, the gross structure of the subunits could be analyzed by
      Western blotting. Similar to alpha(2)delta-1, both alpha(2)delta-2 and -3
      subunits consist of two proteins-a larger alpha(2) and a smaller delta that can
      be separated by reduction. The subunits are also highly N-glycosylated with
      approximately 30 kDa of their mass consisting of oligosaccharides. alpha(2)delta
      1 was detected in all mouse tissues studied, whereas alpha(2)delta-2 was found at
      high levels in brain and heart. The alpha(2)delta-3 subunit was observed only in
      brain. alpha(2)delta-1 and alpha(2)delta-2, but not alpha(2)delta-3, were found
      to bind gabapentin. The K(d) value of gabapentin binding to alpha(2)delta-2 was
      153 nM compared with the higher affinity binding to alpha(2)delta-1 (K(d) = 59
      nM).

PMID- 11306710
TI  - Synthetic phytoceramides induce apoptosis with higher potency than ceramides.
AB  - Ceramides are naturally occurring compounds recognized to mediate apoptosis. N
      acylsphingosines, containing a double bond at carbons 4 and 5 of their sphingoid
      backbone, are thought to be the active form, because N-acylsphinganines with
      completely saturated sphingoid are inactive. In the present study, we synthesized
      a series of N-acyl-4D-ribo-phytosphingosines (phytoceramides) that contain a
      hydroxyl group at carbon 4 and investigated structure-cytotoxicity relationship
      of the presumed functional groups in ceramides. N-Acetylphytoceramide (PCer2) and
      N-hexanoylphytoceramide (PCer6) were found to be more cytotoxic than ceramides as
      determined by released lactate dehydrogenase activity and morphological criteria.
      This was not caused by intracellular conversion of phytoceramides to ceramides,
      because no N-hexanoylsphingosine was formed after incubation of cell lysate with
      PCer6. Among phytoceramides having acyl chains two to eight carbons long, the
      cytotoxicity was highest with five or six carbons. The carbonyl group of the
      amide bond did not seem to be critical, because substitution of the oxygen with
      sulfur did not influence the cytotoxicity. The phytoceramide-induced cell death
      was observed to be apoptotic in nature with the use of terminal deoxynucleotidyl
      transferase dUTP nick-end labeling and propidium iodide staining. Because
      phytoceramides can be readily synthesized from yeast sources, they may present a
      potential and economical alternative to ceramide in future studies and therapies.

PMID- 11306711
TI  - Agonist-dependent delivery of M(2) muscarinic acetylcholine receptors to the cell
      surface after pertussis toxin treatment.
AB  - The internalization of the M(2) muscarinic cholinergic receptor (mAChR) proceeds
      through an atypical pathway that is independent of arrestin and clathrin function
      and shows a unique sensitivity to dynamin when the receptor is expressed in human
      embryonic kidney 293 cells. In this report we demonstrate that the
      internalization of the M(2) mAChR was modulated by activation of heterotrimeric G
      proteins, because treatment with pertussis toxin, which ADP-ribosylates G
      proteins of the G(i/o) family, caused a significant delay in the onset of
      internalization of the M(2) mAChR. The effects of pertussis toxin could not be
      explained by alteration of the agonist-dependent phosphorylation of the M(2)
      mAChR. The modulation of internalization by pertussis toxin was revealed to be
      due to recruitment of intracellular receptors to the cell surface upon agonist
      treatment. Pretreatment with pertussis toxin also greatly increased both the rate
      and extent of recovery of M(2) mAChRs to the cell surface after agonist-mediated
      internalization. These results demonstrate a novel aspect involved in the
      regulation of GPCRs. As with the tightly controlled internalization of GPCRs, the
      delivery of GPCRs to the cell surface is also highly regulated.

PMID- 11306712
TI  - Induction of differentiation in F9 cells and activation of peroxisome
      proliferator-activated receptor delta by valproic acid and its teratogenic
      derivatives.
AB  - The antiepileptic drug valproic acid (VPA) is teratogenic, because it induces
      birth defects in some children of mothers treated for epilepsy. Cellular and
      molecular actions associated with teratogenicity were identified by testing
      differentiation of F9 embryocarcinoma cells. VPA altered cell morphology and
      delayed proliferation. Specific differentiation markers (e.g., c-fos and keratin
      18 mRNA and particularly the activating protein-2 transcription factor protein)
      were induced. This pattern differs from the pattern induced by other teratogens
      or F9 cell-differentiating agents. Induction of differentiation correlated with
      teratogenicity because teratogenic derivatives of VPA, such as (S)-4-yn-VPA,
      induced differentiation, whereas closely related nonteratogenic compounds, such
      as (R)-4-yn-VPA, 2-en-VPA, and 4-methyl-VPA, did not. In the cellular signaling
      network, the peroxisome proliferator-activated receptor delta (PPARdelta) was
      activated selectively by VPA and teratogenic derivatives. Depletion of PPARdelta
      by antisense RNA expression precluded the response of F9 cells to VPA. In
      conclusion, our data show that VPA and its teratogenic derivatives induce a
      specific type of F9 cell differentiation and that PPARdelta is a limiting factor
      in the control of differentiation.

PMID- 11306713
TI  - Identification and characterization of human organic anion transporter 3
      expressing predominantly in the kidney.
AB  - A cDNA encoding a multispecific organic anion transporter 3 (hOAT3) was isolated
      from a human kidney cDNA library. The hOAT3 cDNA consisted of 2179 base pairs
      that encoded a 543-amino-acid residue protein with 12 putative transmembrane
      domains. The deduced amino acid sequence of hOAT3 showed 36 to 51% identity to
      those of other members of the OAT family. Northern blot analysis revealed that
      hOAT3 mRNA is expressed in the kidney, brain, and skeletal muscle. When expressed
      in Xenopus laevis oocytes, hOAT3 mediated the transport of estrone sulfate (K(m)
      = 3.1 microM), p-aminohippurate (K(m) = 87.2 microM), methotrexate (K(m) = 10.9
      microM), and cimetidine (K(m) = 57.4 microM) in a sodium-independent manner.
      hOAT3 also mediated the transport of dehydroepiandrosterone sulfate, ochratoxin
      A, PGE(2), estradiol glucuronide, taurocholate, glutarate, cAMP and uric acid.
      Estrone sulfate did not show any trans-stimulatory effects on either influx or
      efflux of [(3)H]estrone sulfate via hOAT3. hOAT3 interacted with chemically
      heterogeneous anionic compounds, such as nonsteroidal anti-inflammatory drugs,
      diuretics, sulfobromophthalein, penicillin G, bile salts and tetraethyl ammonium
      bromide. The hOAT3 protein was shown to be localized in the basolateral membrane
      of renal proximal tubules and the hOAT3 gene was determined to be located on the
      human chromosome 11q12-q13.3 by fluorescent in situ hybridization analysis. These
      results suggest an important role of hOAT3 in the excretion/detoxification of
      endogenous and exogenous organic anions in the kidney.

PMID- 11306714
TI  - Scabronine G-methylester enhances secretion of neurotrophic factors mediated by
      an activation of protein kinase C-zeta.
AB  - Glial cells release neurotrophic factors that maintain neurons functionally.
      Previously, we have shown that the scabronines isolated from Sarcodon scabrosus
      enhanced the secretion of neurotrophic factors from 1321N1 human astrocytoma
      cells. In the present study, we examined the mechanism of newly synthesized
      scabronine G-methylester (ME)-induced secretion of neurotrophic factors from
      1321N1 cells. The dramatic neuronal differentiation of rat pheochromocytoma cells
      (PC-12) was observed by scabronine G-ME-conditioned medium of 1321N1 cells.
      Scabronine G-ME increased the secretion of nerve growth factor (NGF) and
      interleukin-6 (IL-6) from 1321N1 cells with the enhancement of their mRNA
      expressions. Scabronine G-ME concentration-dependently inhibited the carbachol
      induced inositol phosphate accumulation in 1321N1 cells, which was reversed by
      GF109203X, an inhibitor of protein kinase C (PKC) isoforms. Furthermore,
      GF109203X inhibited the scabronine G-ME-induced mRNA expressions of both NGF and
      IL-6 and the differentiation of PC-12 cells, showing that scabronine G-ME
      activated PKC. Although scabronine G-ME enhanced activities of neither
      conventional nor novel types of PKCs, it translocated PKC-zeta to membranes in
      intact cells and cell-free condition. Furthermore, recombinant PKC-zeta activity
      was also increased by scabronine G-ME, suggesting the involvement of PKC-zeta in
      the effect of scabronine G-ME. Concerning the downstream effectors of the PKC
      zeta, scabronine G-ME translocated nuclear factor-kappaB to nucleus, and enhanced
      its transcriptional activity. In addition, scabronine G-ME caused the degradation
      of inhibitor of nuclear factor-kappaB concentration-dependently, which was
      inhibited by GF109203X. These results suggest that scabronine G-ME potentially
      enhances the secretion of neurotrophic factors from 1321N1 cells mediated via the
      activation of PKC-zeta.

PMID- 11306715
TI  - Diamidine compounds: selective uptake and targeting in Plasmodium falciparum.
AB  - Extensive drug resistance in Plasmodium falciparum emphasizes the urgent
      requirement for novel antimalarial agents. Here we report potent antimalarial
      activity of a number of diamidine compounds. The lead compound pentamidine is
      concentrated 500-fold by erythrocytes infected with P. falciparum. Pentamidine
      accumulation can be blocked by inhibitors of hemoglobin digestion, suggesting
      that the drug binds to ferriprotoporphyrin IX (FPIX). All of the compounds bound
      to FPIX in vitro and inhibited the formation of hemozoin. Furthermore, inhibitors
      of hemoglobin digestion markedly antagonized the antimalarial activity of the
      diamidines, indicating that binding to FPIX is crucial for the activity of
      diamidine drugs. Pentamidine was not accumulated into uninfected erythrocytes.
      Pentamidine transport into infected cells exhibits an initial rapid phase,
      nonsaturable in the micromolar range and sensitive to inhibition by furosemide
      and glibenclamide. Changing the counter-ion in the order Cl(-) < Br(-) < NO(2)(-)
      < I(-) <SCN(-) markedly stimulated pentamidine transport. These data suggest that
      pentamidine is transported although a pore or ion channel with properties similar
      to those of the recently characterized 'induced permeability pathway' on the
      infected red cell membrane. In summary, the diamidines exhibit two levels of
      selectivity against P. falciparum. The route of entry and molecular target are
      both specific to malaria-infected cells and are distinct from targets in other
      protozoa. Drugs that target the hemoglobin degradation pathway of malaria
      parasites have a proven record of accomplishment. The employment of induced
      permeability pathways to access this target represents a novel approach to
      antiparasite chemotherapy and offers an additional level of selectivity.

PMID- 11306716
TI  - Antimineralocorticoid 11beta-substituted spirolactones exhibit androgen receptor
      agonistic activity: a structure function study.
AB  - In humans, spironolactone and mespirenone are well known antimineralocorticoids
      without C-11beta substituents. These compounds display antagonist properties by
      acting through the human androgen receptor (hAR). In contrast, we demonstrate
      here that synthetic mineralocorticoid antagonists bearing hydrophobic C-11beta
      substituents and C-17gamma-lactone are potent hAR agonists in vitro. The three
      dimensional construction of both the ligand binding domain (LBD) of the hAR and
      the human mineralocorticoid receptor (hMR), based on the crystal structure of the
      LBD of the human progesterone receptor, revealed not only that the interactions
      with the steroidal A- and D-rings seemed to be crucial for stabilization of
      active hMR or hAR conformation, but that other steroidal substitutions could
      influence the agonist versus antagonist activity of ligands. The docking of
      synthetic compounds bearing C-11beta hydrophobic substituents within the ligand
      binding pocket of hAR demonstrated that precise positions of the steroid, such as
      C-11 and C-17, are in close contact with some residues on the receptor, C-11 with
      Gly 708 and C-17 with Asn705 and Thr877. These contacts are crucial for the
      stabilization of the active receptor conformation. Mutation of Asn705 by alanine
      altered the 11beta-substituted spirolactone-mediated trans-activation function of
      hAR, suggesting an anchoring of the C-17-lactone carbonyl group (C-22) with this
      residue. The stabilizing effect of the H12 helix in its active conformation is
      also induced by hydrophobic contacts between the Gly708 and C-11beta
      substituents, as recently observed with the A773G-hMR mutant in the presence of
      similar drugs. The study of the role of these substituents suggests efficient new
      directions for the drug design of selective androgen agonists.

PMID- 11306717
TI  - Involvement of caveolin in ligand-induced recruitment and internalization of A(1)
      adenosine receptor and adenosine deaminase in an epithelial cell line.
AB  - Chronic exposure of A(1) adenosine receptors (A(1)R) to A(1)R agonists leads to
      activation, phosphorylation, desensitization, and internalization to
      intracellular compartments of the receptor. Desensitization and internalization
      of A(1)R is modulated by adenosine deaminase (ADA), an enzyme that regulates the
      extracellular concentration of adenosine. ADA interacts with A(1)R on the cell
      surface of the smooth muscle cell line DDT1 MF-2, and both proteins are
      internalized following agonist stimulation of the receptor. The mechanism
      involved in A(1)R and ADA internalization upon agonist exposure is poorly
      understood in epithelial cells. In this report, we show that A(1)R and ADA
      interact in LLC-PK(1) epithelial cells. Exposure of LLC-PK(1) cells to A(1)R
      agonists induces aggregation of A(1)R and ADA on the cell surface and their
      translocation to intracellular compartments. Biochemical and cell biology assays
      were used to characterize the intracellular vesicles containing both proteins
      after agonist treatment. A(1)R and ADA colocalized together with the rafts marker
      protein caveolin. Filipin, a sterol-binding agent that disrupts rafts (small
      microdomains of the plasma membrane), was able to inhibit A(1)R internalization.
      In contrast, acid treatment of the cells, which disrupts internalization via
      clathrin-coated vesicles, did not inhibit agonist-stimulated A(1)R
      internalization. We demonstrated that A(1)R agonist N(6)-(R)-phenylisopropyl
      adenosine promotes the translocation of A(1)R into low-density gradient fractions
      containing caveolin. Furthermore, a direct interaction of the C-terminal domain
      of A(1)R with caveolin-1 was demonstrated by pull down experiments. These results
      indicate that A(1)R and ADA form a stable complex in the cell surface of LLC
      PK(1) cells and that agonist-induced internalization of the A(1) adenosine
      receptor and ADA is mediated by clathrin-independent endocytosis.

PMID- 11306718
TI  - Carboxypeptidase D is up-regulated in raw 264.7 macrophages and stimulates nitric
      oxide synthesis by cells in arginine-free medium.
AB  - Membrane-bound carboxypeptidase D (CPD) is a B-type carboxypeptidase that
      specifically cleaves C-terminal Arg or Lys from peptides and proteins. RAW 264.7
      cells contained significant membrane-bound CPD activity as shown by activity
      assays and immunoprecipitation. To determine whether CPD can increase nitric
      oxide (NO) synthesis by releasing precursor Arg, cells were activated in Arg-free
      medium with 50 U/ml interferon-gamma (IFN-gamma) and 0.1 microg/ml
      lipopolysaccharide (LPS) to up-regulate inducible NO synthase. Addition of the
      specific carboxypeptidase substrate, 200 microM furylacryloyl-Ala-Arg, stimulated
      NO production by 6-fold and this effect was blocked 83% by a specific inhibitor,
      DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA). MGTA did not
      inhibit NO synthesis stimulated by added free Arg. Lys, an inhibitor of Arg
      transport, also blocked the effect of the carboxypeptidase substrate. In cells
      stimulated with IFN-gamma and LPS in Arg-free medium, CPD activity increased 2-
      to 3-fold between 8 and 16 h after treatment, but did not change in cells
      stimulated in medium containing 0.4 mM Arg. The NO synthase inhibitor N
      monomethyl-L-arginine blocked the inhibitory Arg effect and the NO donor S
      nitroso-acetylpenicillamine mimicked it, indicating that high levels of NO block
      the up-regulation of CPD. Immunohistochemical staining and Western analysis
      revealed an increase in CPD protein, and Northern analysis showed increased CPD
      mRNA upon stimulation of cells in Arg-free medium. CPD was localized both on the
      plasma membrane and in the Golgi. These data suggest that CPD expression is
      enhanced during inflammatory processes and may stimulate NO production by
      cleaving Arg from peptide substrates.

PMID- 11306719
TI  - Rhodostomin, a snake venom disintegrin, inhibits angiogenesis elicited by basic
      fibroblast growth factor and suppresses tumor growth by a selective
      alpha(v)beta(3) blockade of endothelial cells.
AB  - Angiogenesis consists of the proliferation, migration, and differentiation of
      endothelial cells, although angiogenic factor and integrin-extracellular matrix
      interaction modulate this process. We report here that a snake venom-derived
      disintegrin, rhodostomin, inhibited distinct steps in angiogenesis elicited by
      basic fibroblast growth factor (bFGF), and also suppressed in vivo murine
      melanoma tumor growth. Rhodostomin dose-dependently inhibited bFGF-induced human
      umbilical vein endothelial cell (HUVEC) proliferation as examined by cell number
      count, metabolic activity, and BrdU incorporation assays with submicromolar
      IC(50) values. However, it apparently did not affect the viability of murine
      B16F10 melanoma cells, even up to 50 microM. Rhodostomin also inhibited HUVEC
      migration and invasion evoked by bFGF, and tube formation of bFGF-treated HUVECs
      in Matrigel. Moreover, rhodostomin selectively inhibited bFGF-, but not vascular
      endothelial growth factor-associated angiogenesis in the chick chorioallantoic
      membrane model. Furthermore, rhodostomin blocked both bFGF- and B16F10-induced
      neovascularization in murine Matrigel plug model and suppressed the growth of
      subcutaneously inoculated B16F10 solid tumor, leading to a prolonged survival of
      the rhodostomin-treated C57BL/6 mice. The antiangiogenic effect of rhodostomin on
      bFGF-treated HUVECs is related to the integrin alpha(v)beta(3) blockade, as
      evidenced by its selective inhibition on the binding of 7E3, a monoclonal
      antibody (mAb) raised against alpha(v)beta(3,) but not that of P1F6, an
      alpha(v)beta(5) mAb toward both naive and bFGF-primed HUVECs. Moreover, 7E3
      specifically blocked fluorescein isothiocyanate-conjugated rhodostomin binding to
      HUVEC, whereas P1F6 and anti-integrin alpha(2), alpha(3), alpha(4), or alpha(5)
      mAbs did not.

PMID- 11306720
TI  - Molecular mechanism for agonist-promoted alpha(2A)-adrenoceptor activation by
      norepinephrine and epinephrine.
AB  - We present a mechanism for agonist-promoted alpha(2A)-adrenergic receptor
      (alpha(2A)-AR) activation based on structural, pharmacological, and theoretical
      evidence of the interactions between phenethylamine ligands and alpha(2A)-AR. In
      this study, we have: 1) isolated enantiomerically pure phenethylamines that
      differ both in their chirality about the beta-carbon, and in the presence/absence
      of one or more hydroxyl groups: the beta-OH and the catecholic meta- and para-OH
      groups; 2) used [(3)H]UK-14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6
      quinoxalinamine; agonist] and [(3)H]RX821002 [2-(2-methoxy-1,4-benzodioxan-2-yl)
      2-imidazoline; antagonist] competition binding assays to determine binding
      affinities of these ligands to the high- and low-affinity forms of alpha(2A)-AR;
      3) tested the ability of the ligands to promote receptor activation by measuring
      agonist-induced stimulation of [(35)S]GTPgammaS binding in isolated cell
      membranes; and 4) used automated docking methods and our alpha(2A)-AR model to
      predict the binding modes of the ligands inside the alpha(2A)-AR binding site.
      The ligand molecules are sequentially missing different functional groups, and we
      have correlated the structural features of the ligands and ligand-receptor
      interactions with experimental ligand binding and receptor activation data. Based
      on the analysis, we show that structural rearrangements in transmembrane helix
      (TM) 5 could take place upon binding and subsequent activation of alpha(2A)-AR by
      phenethylamine agonists. We suggest that the following residues are important in
      phenethylamine interactions with alpha(2A)-AR: Asp113 (D(3.32)), Val114
      (V(3.33)), and Thr118 (T(3.37)) in TM3; Ser200 (S(5.42)), Cys201 (C(5.43)), and
      Ser204 (S(5.46)) in TM5; Phe391 (F(6.52)) and Tyr394 (Y(6.55)) in TM6; and Phe411
      (F(7.38)) and Phe412 (F(7.39)) in TM7.

PMID- 11306723
TI  - Update on the treatment of multiple myeloma.
AB  - The patient with multiple myeloma should be carefully evaluated from the
      standpoint of symptoms, physical findings, and laboratory data. If there are no
      symptoms or evidence of early or impending complications, the patient should not
      be treated. He or she should be followed and treatment delayed until progression
      of the disease occurs. If the patient is younger than 70 years, autologous
      peripheral blood stem cell transplantation should be considered. Hematopoietic
      stem cells should be collected before the patient is exposed to alkylating
      agents. If the patient is older than 70 years, chemotherapy is indicated. The two
      major shortcomings of autologous stem cell transplantation are: A) failure to
      eradicate myeloma, and B) contamination of autologous peripheral blood stem
      cells. Most physicians initially treat the patient with vincristine, doxorubicin
      (Adriamycin), and dexamethasone (VAD) for three to four months and then collect
      the peripheral blood stem cells. One can then proceed with transplant or treat
      the patient with alkylating agents and delay the transplant until the patient
      progresses. In a prospective trial comparing autologous bone marrow
      transplantation with conventional chemotherapy, five-year overall survival
      favored the transplant group (52% versus 12%). In a randomized trial of 400
      patients from France, there was no difference in event-free or overall survival
      between double and single autologous stem cell transplant when evaluated at two
      years. In a subsequent evaluation, patients with a low beta(2)-microglobulin
      value at diagnosis appeared to have better results with a double transplant.
      There is no evidence that combinations of chemotherapeutic agents are more
      effective than melphalan and prednisone. Allogeneic transplantation is associated
      with a high mortality. Depletion of T-cells or a mini-allogeneic transplant may
      be beneficial in an effort to reduce mortality. Thalidomide produces objective
      response in approximately 30% of refractory patients. The use of intravenous
      bisphosphonates is recommended for patients with skeletal lesions. Hypercalcemia
      and renal failure must be treated promptly.

PMID- 11306724
TI  - Clinical significance of occult metastatic cells in bone marrow of breast cancer
      patients.
AB  - The early and clinically occult spread of viable tumor cells to the organism is
      increasingly considered a hallmark in cancer progression, as emerging data
      suggest that these cells are precursors of subsequent distant relapse. Using
      monoclonal antibodies to epithelial cytokeratins or tumor-associated cell
      membrane glycoproteins, individual carcinoma cells can be detected on cytologic
      bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical
      studies have shown that the presence of these immunostained cells in bone marrow,
      as a frequent site of overt metastases, is prognostically relevant with regard to
      relapse-free and overall survival. This screening approach may be, therefore,
      used to improve tumor staging and guide the stratification of patients for
      adjuvant therapy in clinical trials. Another promising application is monitoring
      the response of micrometastatic cells to adjuvant therapies, which, at present,
      can only be assessed retrospectively after an extended period of clinical follow
      up. The present review summarizes the current data on the clinical significance
      of occult metastatic breast cancer cells in bone marrow.

PMID- 11306725
TI  - Chemotherapy of metastatic breast cancer: what to expect in 2001 and beyond.
AB  - Chemotherapy plays an important role in the management of metastatic breast
      cancer. The anthracyclines (doxorubicin, epirubicin) and the taxanes (paclitaxel,
      docetaxel) are considered the most active agents for patients with advanced
      breast cancer. Traditionally, the anthracyclines have been used in combination
      with cyclophosphamide and 5-fluorouracil (FAC, FEC). The taxanes have single
      agent activity similar to older combination chemotherapy treatments. There is
      great interest in developing anthracycline/taxane combinations. Capecitabine is
      indicated for patients who progress after anthracycline and taxane therapy.
      Vinorelbine and gemcitabine have activity in patients with metastatic breast
      cancer and are commonly used as third- and fourth-line palliative therapy. The
      role of high-dose chemotherapy is not well-defined and remains experimental.
      Novel cytotoxic therapy strategies include the development of anthracycline,
      taxane, and oral fluoropyrimidine analogues; antifolates; topoisomerase I
      inhibitors, and multidrug resistance inhibitors. A better understanding of the
      biology of breast cancer is providing novel treatment approaches. Oncogenes and
      tumor-supressor genes are emerging as important targets for therapy. Trastuzumab,
      a monoclonal antibody directed against the Her-2/neu protein, has been shown to
      prolong survival in patients with metastatic breast cancer. Other novel biologic
      therapies interfere with signal transduction pathways and angiogenesis. The
      challenge for the next decade will be to integrate these promising agents in the
      management of metastatic and primary breast cancer.

PMID- 11306726
TI  - Early lung cancer action project: a summary of the findings on baseline
      screening.
AB  - PURPOSE: The Early Lung Cancer Action Project (ELCAP) is designed to evaluate
      baseline and annual repeat screening by low radiation dose computed tomography
      (low-dose CT) in persons at high-risk for lung cancer. METHODS: Since starting in
      1993, the ELCAP has enrolled 1,000 asymptomatic persons, 60 years of age or
      older, with at least 10 pack-years (1 pack per day for 10 years, or 2 packs per
      day for 5 years) of cigarette smoking, no prior cancer, and medically fit to
      undergo thoracic surgery. After a structured interview and informed consent,
      baseline chest radiographs and low-dose CT were obtained on each subject. The
      diagnostic work-up of screen-detected noncalcified pulmonary nodules (NCN) was
      guided by ELCAP recommendations which included short-term high-resolution CT
      follow-up for the smallest nodules. Baseline RESULTS: On low-dose CT at baseline
      compared to chest radiography, NCN were detected three times as commonly (23%
      versus 7%), malignancies four times as commonly (2.7% versus 0.7%), and stage I
      malignancies six times as commonly (2.3% versus 0.4%). Of the 27 CT-detected
      cancers, 96% (26/27) were resectable; 85% (23/27) were stage I, and 83% (19 of
      the 23 stage I) were not seen on chest radiography. Following the ELCAP
      recommendations, biopsies were performed on 28 of the 233 subjects with NCN; 27
      had a malignant and one a benign NCN. Another three individuals underwent biopsy
      outside of the ELCAP recommendations; all had benign NCNS: No one had thoracotomy
      for a benign nodule. CONCLUSION: Baseline CT screening for lung cancer provides
      for detecting the disease at earlier and presumably more commonly curable stages
      in a cost-effective manner.

PMID- 11306727
TI  - Noncardiogenic pulmonary edema: an unusual and serious complication of anticancer
      therapy.
AB  - Noncardiogenic pulmonary edema (NCPE) is a rare and less well-recognizable
      pulmonotoxic syndrome of anticancer therapy than pneumonitis/fibrosis. NCPE is a
      clinical syndrome characterized by simultaneous presence of severe hypoxemia,
      bilateral alveolar infiltrates on chest radiograph, and no evidence of left
      atrial hypertension/congestive heart failure. The diagnosis of drug-related NCPE
      relies upon documented exclusion of any infectious, metabolic, or cancer-related
      causes. The time proximity to therapy with drugs that are known to precipitate
      NCPE, any preceding episodes of flu-like symptoms during previous chemotherapy
      courses and possible response to corticosteroids may further support such a
      diagnosis. Cancer therapeutic agents clearly associated with NCPE are cytarabine,
      gemcitabine, and interleukin-2, as well as all-trans retinoic acid in acute
      promyelocytic leukemia patients, while a few other compounds have rarely or
      occasionally been implicated. The pathophysiology of lung injury in drug-induced
      NCPE remains unclear. There are indications suggesting that both a direct
      cytotoxic insult to the lung epithelial cells and induction of a cytokine
      triggered inflammatory response may be involved in its pathogenesis. By
      distinction to drug-induced pulmonary pneumonitis that may lead to permanent
      pulmonary fibrosis, NCPE if not fatal, can be reversed upon prompt recognition,
      following immediate discontinuation of the offensive drug and start of intensive
      supportive treatment and intravenous corticosteroids.

PMID- 11306728
TI  - Hepatotoxicity of chemotherapy.
AB  - After assessment of tumor histology, the next important factor to consider in the
      selection of a chemotherapy regime is organ function. Patients who are to receive
      chemotherapy require careful assessment of liver function prior to treatment to
      determine which drugs may not be appropriate, and which drug doses should be
      modified. Following therapy abnormalities of liver function tests may be due to
      the therapy rather than to progressive disease, and this distinction is of
      critical importance. Furthermore, not all abnormalities in liver function are due
      to the tumor or its treatment, and other processes, such as hepatitis, must be
      kept in mind. This article reviews the hepatic toxicity of chemotherapeutic
      agents, and suggests dose modifications based upon liver function abnormalities.
      Emphasis is placed on agents known to be hepatotoxic, and those agents with
      hepatic metabolism.

PMID- 11306729
TI  - Treatment of localized prostate cancer with intermittent triple androgen
      blockade: preliminary results in 110 consecutive patients.
AB  - OBJECTIVES: To determine the effectiveness of triple androgen blockade as an
      alternative to watchful waiting, radical prostatectomy or radiation therapy in
      the management of patients with clinical stage T1 to T3 prostate cancer. METHODS:
      The records of 110 consecutive patients were retrospectively evaluated. Patients
      were treated with a three-drug androgen blockade regimen, consisting of a
      luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) plus an
      antiandrogen (flutamide or bicalutamide) plus finasteride (a 5-alpha-reductase
      inhibitor), followed by finasteride maintenance therapy, as the sole
      intervention. All patients refused local therapy and had their prostates intact.
      Determinants of efficacy included serum prostate-specific antigen (PSA) levels
      and disease-specific survival. RESULTS: Patients were treated for a median of 13
      months with triple androgen blockade. At baseline, mean PSA level was 13.2 +/-
      1.2 ng/ml (range, 0.39-100 ng/ml), and mean Gleason score was 6.6 +/- 0.1 (range,
      4-10). During treatment, PSA levels declined to < or =0.1 ng/ml in all patients,
      with a median time of 3 months. After a median follow-up of 36 months since
      initiation of treatment, PSA levels have remained stable in 105 of 110 patients
      (95.5%). At a median follow-up of 55 months (range, 38-125 months), the mean PSA
      level for the first 57 patients treated in this series is 1.88 +/- 0.1 (range, 0
      11.0 ng/ml). Only 9 of 110 (8.1%) patients have a PSA level > or =4.0 ng/ml. To
      date, no patient has received a second cycle of hormone blockade. CONCLUSIONS:
      Although median follow-up is short, triple androgen blockade therapy followed by
      finasteride maintenance appears to be a promising alternative for the management
      of patients with clinically localized or locally advanced prostate cancer.
      Further study of this approach is warranted.

PMID- 11306730
TI  - Progressing prostate carcinoma.
AB  - In the Karnell Cancer Center Grand Rounds, we present a patient who underwent
      radical prostatectomy with bilateral pelvic lymphadenectomy, but had positive
      margins and subsequently developed local recurrence and then systemic disease.
      Pathologic and radiologic aspects of his disease are discussed. Therapeutic
      options at different stages of the disease are examined from the point of view of
      the urologist, radiation oncologist, and medical oncologist. The surgical portion
      of the discussion focuses on the selection of initial therapy. Both the selection
      of surgical candidates and choice of pre- or post-operative therapy in patients
      can be aided by prognostic tools looking at several variables, including prostate
      specific antigen (PSA) level, Gleason score of the tumor, seminal vesicle
      invasion, extracapsular invasion, and lymph node involvement. Low-risk patients
      can be treated with monotherapy, such as radical prostatectomy, external beam
      radiation therapy, prostate brachytherapy, or cryosurgical ablation of the
      prostate. Higher risk patients may require adjuvant and possibly neoadjuvant
      therapy in addition. The radiation portion of the discussion focuses on the use
      of radiation therapy as salvage for relapsing disease. Of particular importance
      is the point that treating high-risk patients whose PSA levels have started to
      rise but are less than 1 ng/ml results in a long-term PSA control rate as high as
      75%, but that limiting the use of salvage radiation therapy to patients with high
      PSA levels or biopsy confirmation of local recurrence in the face of a negative
      bone scan results in biochemical long-term control of less than 40%. In the
      medical oncology part of the discussion, the major focus is on the use of
      chemotherapy to treat patients whose disease has become resistant to hormonal
      therapy. Mitoxantrone plus a corticosteroid has been found to offer significant
      palliation for such patients. Combination therapy with estramustine plus taxanes,
      other microtubule inhibitors, or other agents such as topoisomerase II
      inhibitors, has been found to cause shrinkage of measurable soft tissue disease
      and diminution of serum PSA levels. The development of effective hormonal and
      chemotherapeutic drugs for treatment of metastatic disease has led to new
      interest in adjuvant and neoadjuvant therapy of high-risk patients.

PMID- 11306732
TI  - The molecular perspective: cytochrome p450.

PMID- 11306731
TI  - Caring for colleagues.
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The
      Schwartz Center is a non-profit organization dedicated to supporting and
      advancing compassionate health care delivery, which provides hope to the patient,
      support to caregivers, and sustenance to the healing process. The center sponsors
      the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers
      reflect on important psychosocial issues faced by patients, their families, and
      their caregivers, and gain insight and support from fellow staff members. Caring
      for colleagues who develop cancer is a privilege woven with an extra dimension
      caregiver-patient issues. As well as stretching the usual need for a supportive
      relationship, when one of the health care team develops cancer it particularly
      provokes concerns about our own mortality. The case is presented of a well-known
      physician who developed a second cancer and has been cared for at the MGH Cancer
      Center Staff discuss her care as it has been effected by her status as a
      colleague. They perceived unique barriers to optimal care such as assumptions
      about the patient's level of medical knowledge, and technical, informational,
      emotional, and hierarchical issues that may obstruct the development of a
      trusting relationship between caregivers and the physician/patient. Emotional
      stress may prevent the sharing of an accurate prognosis. In the case under
      consideration, the patient had a frank and open attitude to her cancer yet her
      caregivers were concerned about continual breeches of patient confidentiality.
      Despite the many potential problems inherent when the caregiver becomes the
      patient, this case discussion was a poignant reminder of the unique challenges of
      every experience with cancer and the weighty privilege of being involved with
      patient care.

PMID- 11306733
TI  - First symposium of novel molecular targets for cancer therapy.

PMID- 11306737
TI  - Doppler aortic flow velocity measurement in healthy children.
AB  - To determine normal values for Doppler parameters of left ventricular function,
      ascending aortic blood flow velocity was measured by pulsed wave Doppler
      echocardiography in 63 healthy children with body surface area (BSA) < 1 m(2)
      (age < 10 yr). Peak velocity was independent of sex, but increased with body
      size. Mean acceleration was related to peak velocity (r = 0.75, p < 0.0001). Both
      stroke distance and ejection time had strong negative correlations with heart
      rate and positive correlations with BSA, suggesting that these parameters should
      be evaluated in relation to heart rate and body size. Mean intra- and
      interobserver variability for peak velocity, ejection time, stroke and minute
      distance ranged from 3 to 7%, whereas variability for acceleration time was 9 to
      13%. These data may be used as reference values for the assessment of hemodynamic
      states in young children with cardiac disease.

PMID- 11306736
TI  - The levels of MDM2 protein are decreased by a proteasome-mediated proteolysis
      prior to caspase-3-dependent pRb and PARP cleavages.
AB  - MDM2 is a substrate of caspase-3 in p53-mediated apoptosis. In addition, MDM2
      mediates its own ubiquitination in a RING finger-dependent manner. Thus, we
      investigated whether MDM2 is degraded through a ubiquitin-dependent proteasome
      pathway in the absence of p53. When HL-60 cells, p53 null, were treated with
      etoposide, MDM2 was markedly decreased prior to caspase-3-dependent
      retinoblastoma tumor suppressor protein (pRb) and poly (ADP- ribose) polymerase
      (PARP) cleavages. Moreover, down-regulation of MDM2 level was not coupled with
      its mRNA down-regulation. However, the level of MDM2 was partially restored by
      proteasome inhibitors such as LLnL and lactacystin, even in the presence of
      etoposide. Our results suggest that, in the p53 null status, MDM2 protein level
      is decreased by proteasome-mediated proteolysis prior to caspase-3-dependent PARP
      and pRb cleavages.

PMID- 11306738
TI  - Detection of fetal erythroid cells from maternal blood using fluorescence in situ
      hybridization and liquid culture.
AB  - Fetal nucleated erythrocytes circulating in maternal blood are a potential source
      of fetal DNA for noninvasive prenatal genetic diagnosis. However, the estimated
      ratio of fetal to maternal cells is extremely small. In order to enrich these
      cells, we performed direct culture using a two-phase liquid system. Mononuclear
      cells were obtained from maternal blood samples at 8-10(+3) weeks of gestation
      and cultured in the first phase. After 4-5 days, the nonadherent cells were
      harvested and recultured with erythropoietin in the second phase for another 3-5
      days. We examined cellular morphology, and counted the number of benzidine-
      positive cells and the percentage of glycophorin A/CD71 positive erythroid cells.
      We also did Kleihauer-Betke stain for Hb F, polymerase chain reaction (PCR) for
      SRY/DYZ1, chromosome analysis, and fluorescence in situ hybridization (FISH). The
      number of total erythroid cells reached about 0.1 x 10(6)-1.0 x 10(6)/mL with a
      purity of 84.0-97.3%. Hb F stain showed total erythroid cells of approximately
      0.4 x 10(4)-9.8 x 10(4)/mL. Male DNA was detected in one case by PCR. In this
      case, the XY karyotype was confirmed by FISH and amniocentesis. This approach
      provides enriched source of fetal cells for further prenatal genetic analysis
      without complicated separation or sorting procedures.

PMID- 11306739
TI  - A clinicopathologic study on three cases of constrictive bronchiolitis.
AB  - We describe the characteristic clinical and pathologic findings of three cases of
      constrictive bronchiolitis. All three patients were middle-aged women with
      chronic respiratory illness characterized by chronic cough, dyspnea, mild to
      severe obstructive pulmonary dysfunction, relatively normal chest radiographs
      with occasional peribronchial infiltration, and lack of response to
      bronchodilators or prednisolone. The patients also had medical diseases such as
      non-Hodgkin's lymphoma and hyperprolactinemia in case 1 and 3, respectively. None
      of the patients smoked cigarettes and had clinical evidence of recent viral lower
      respiratory tract infection. Histologic study by open lung biopsy revealed a
      spectrum of changes ranging from active cellular bronchiolitis to obliterative
      peribronchiolar fibrosis. The intervening interstitial and alveolar areas showed
      no remarkable lesion. Immunohistochemically, the bronchiolar or peribronchiolar
      inflammatory infiltrates mainly comprised of mixed T- and B-lymphocytes. It may
      be possible that the active form of constrictive bronchiolitis is initiated by
      attendant lymphocytic inflammation of the airways, which is followed by fibrous
      obliteration of bronchioles.

PMID- 11306740
TI  - Prevalences of symptoms of asthma and other allergic diseases in korean children:
      a nationwide questionnaire survey.
AB  - The purpose of this study was to estimate the national prevalence of childhood
      asthma and other allergic diseases in Korea, and to determine potential risk
      factors for the diseases. Stratified random samples of 42,886 were selected from
      34 elementary (6-12 yr olds) and 34 middle schools (12-15 yr olds) nationwide,
      and 38,955 were in the final analysis. The Korean-translated modified version of
      the International Study of Asthma and Allergies in Childhood questionnaire was
      used in this cross-sectional survey. Twelve-month prevalences of the symptoms of
      asthma, rhinoconjunctivitis, and flexural eczema were 8.7%, 10.5%, 7.3% in 6-12
      yr olds, and 8.2%, 10.0%, 3.9% in 12-15 yr olds, respectively. For allergic
      conjunctivitis, food allergy, and drug allergy, the prevalences in 6-12 yr olds
      were 11.2%, 6.5%, and 1.5%, respectively. Asthma and flexural eczema decreased
      significantly with age. Other significant risk factors were also noted. For 6-12
      yr-old asthma, adjusted odds ratio (aOR) of body mass index was 1.21 with 95%
      confidence interval (CI) 1.0-1.48, aOR of passive smoking was 1.37 with 95%CI
      1.24-1.51, aOR of carpet use was 1.28 with 95%CI 1.10-1.49. For 6-12 yr-old
      eczema, aOR of affluence was 1.22 with 95%CI 1.07-1.39. The control of obesity
      and passive smoking would be the most important preventive measures of allergic
      diseases.

PMID- 11306741
TI  - Apoptosis, bcl2 expression, and cell cycle analyses in nickel(II)-treated normal
      rat kidney cells.
AB  - Nickel compounds are carcinogenic to human and are potent inducers of kidney and
      lung tumors in experimental animals. In this study, the effects of nickel(II)
      acetate on apoptosis, cell cycle and bcl2 expression in normal rat kidney (NRK-
      52E) cells were investigated. Nickel(II) induced apoptosis in NRK-52E cells as
      demonstrated by DNA laddering. Apparent DNA laddering was observed in cells
      treated with 480 microM for 48 hr. In the flow cytometric analysis using
      propidium iodide fluorescence, an increase of cell proportion in G2/M phase was
      shown in cells exposed to at least 320 microM of nickel(II) acetate, from 7.7%
      for 0 microM of nickel(II) to 16.5% for 480 microM of nickel(II) acetate.
      Induction of apoptotic cell death by nickel(II) was accompanied by reduction of
      bcl2 protein expression, while the level of p53 protein was not changed. Taken
      together, our data indicate that nickel(II)-induced apoptosis in NRK-52E cells is
      accompanied by G2/M cell cycle arrest, regardless of p53 function, and that bcl2
      mediated signaling pathway may be involved in positive regulation of nickel(II)
      induced apoptotic cell death in NRK-52E cells.

PMID- 11306742
TI  - Human papillomavirus 16/18 expression of endocervical glandular lesions:
      relationship with p53 and MIB-1 Expressions.
AB  - The pathogenesis of endocervical glandular lesions are not clearly understood.
      The aims of this study are to evaluate the etiologic role of human papillomavirus
      (HPV) 16/18 and the relationship of HPV 16/18, p53 and MIB-1 expressions in
      endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and
      adenocarcinoma. The materials included 14 endocervical adenocarcinoma and 5 AIS
      and 18 high grade EGD and 39 low grade EGD. Immunohistochemistry for p53 and MIB
      1, and in situ PCR for HPV 16/18 were done. HPV 16/18 positivity was 84.2%, 16.7%
      and 17.9% in malignant glandular lesion (adenocarcinoma and AIS), high grade EGD
      and low grade EGD, respectively. P53 protein expression rates of malignant
      glandular lesions, high grade EGD and low grade EGD were 31.6%, 11.1%, and 0%,
      respectively. High MIB-1 labelling index was found in 73.7% of malignant
      glandular lesions, but in only 5.7% and 3.6% of high and low grade EGD,
      respectively. There were statistically significant differences in HPV 16/18, p53
      and MIB-1 expressions between malignant endocervical glandular lesions and EGD,
      but no significant difference in p53 and MIB-1 expressions in relation to HPV
      16/18 expression. In malignant endocervical glandular lesions, HPV 16/18
      infection may be a major causative factor, but not be related to p53 and MIB-1
      expressions.

PMID- 11306744
TI  - Effect of graded running on esophageal motility and gastroesophageal reflux in
      fed volunteers.
AB  - The effects of different grades of running on esophageal motility and
      gastroesophageal reflux in the fed state were evaluated. We studied healthy
      volunteers (male: 12, age: 27 +/- 5 yr) using ambulatory esophageal manometry, pH
      catheter and portable digital data recorder. Each exercise was performed 30 min
      after meal, with 20 min of rest between exercises. Subjects exercised on a
      treadmill at 40% and 70% maximal heart rate. The number of gastroesophageal
      reflux episodes, the duration of esophageal acid exposure and percent time pH
      below 4 were significantly (p < 0.01) increased during exercise at 70% maximal
      heart rate. The frequency of contraction (contraction/min) (p < 0.05), frequency
      of repetition (p < 0.01), percent of simultaneous contraction (p < 0.01), percent
      of above 100 mmHg amplitude (p < 0.05), and frequency of 2-peak contraction (p <
      0.01) were significantly increased during exercise at 70% maximal heart rate.
      However, median amplitude and median duration showed no significant changes
      between each exercise session. Postprandial running exercises induce
      gastroesophageal reflux, which correlates with exercise intensity. These effects
      are mediated by disorganized esophageal motility.

PMID- 11306743
TI  - Clinical impacts of tumor cell contamination of hematopoietic stem cell products
      in metastatic breast cancer patients undergoing autologous peripheral blood stem
      cell transplantation: multicenter trial.
AB  - To determine whether the tumor cell contamination of peripheral blood stem cells
      influences clinical impacts on high-dose chemotherapy in patients with metastatic
      breast cancer, we analyzed carcinoembryonic antigen (CEA) mRNA in the apheresis
      products by nested RT-PCR (reverse transcriptase-polymerase chain reaction). A
      total of 38 metastatic breast cancer patients and ten normal healthy subjects as
      a negative control were included. Twenty out of 38 (51.3%) apheresis products
      from patients with metastatic breast cancer were positive for CEA mRNA. CEA mRNA
      was noted in 54.8% (17/31) of patients mobilized with chemotherapy plus G-CSF and
      42.8% (3/7) of patients with G-CSF alone. There was no significant difference in
      age, estrogen receptor, menopausal status, mobilization method, disease free
      interval, or number of metastasis sites (1 vs > or = 2) between positive and
      negative groups. The presence of CEA mRNA in apheresis products did not influence
      the time to progression and overall survival in both groups. However, both the
      univariate and the multivariate analysis disclosed that the number of metastasis
      was associated with survival significantly. We suggest that the tumor cell
      contamination does not predict poor treatment outcome in patients with metastatic
      breast cancer.

PMID- 11306745
TI  - Lack of relationship between vitamin D receptor polymorphism and bone erosion in
      rheumatoid arthritis.
AB  - We performed this study to investigate the possible association between vitamin D
      receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid
      arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were
      enrolled and two control groups were selected. The focal bone erosion score was
      assessed by modified Sharp's method. Genotyping of VDR polymorphisms was
      performed by polymerase chain reaction and restriction fragment length
      polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the
      distribution of VDR genotype in Korean population was different from Caucasians.
      The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and
      in control groups. The frequency distribution of the Taq I and Bsm I genotype was
      not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb,
      5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb,
      8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion
      score (mean +/- SD) according to the VDR genotypes of RA patients (TT, 0.92 +/-
      1.79; Tt, 0.4 +/- 0.79; Bb, 0.43 +/- 0.80; bb, 0.92 +/- 1.79; p > 0.05). In
      conclusion, these results suggest that VDR gene polymorphisms are not associated
      with the focal bone erosion in RA patients in Korea.

PMID- 11306746
TI  - Cephalic spreading levels after volumetric caudal epidural injections in chronic
      low back pain.
AB  - The volumetric caudal epidural steroid injection has been advocated to facilitate
      the delivery of medications to the lesion site. This study was aimed to examine
      the actual spreading patterns of this technique, using epidurogram. A total of 32
      patients with chronic low back pain accompanied by radiculopathy of various
      causes (degenerative spondylosis, herniated nucleus pulposus, spondylolisthesis,
      and spinal stenosis) were included. The volumetric caudal epidural injection of
      the 10 mL mixture of contrast medium 5 mL, 0.5% bupivacaine 1 mL, triamcinolone
      1.5 mL (60 mg) and normal saline 25 mL was performed. Immediately after the
      cessation of the first spread, the subsequent solution of another 10 mL of
      contrast medium 5 mL, 0.5% bupivacaine 1 mL and normal saline 4 mL was injected.
      This procedure was repeated serially until the total volume to be 50 mL.
      Continuous fluoroscopic imaging was obtained after each injection. Average time
      taken to complete the study was 37 sec per every 10 mL. The spreading levels of
      the mixture were distributed mainly at mid to lower lumbar area in the majority
      of the patients. During the subsequent injections, the levels were not changed
      significantly. This was thought to be due to the minimal resistance in cephalad
      direction, anatomic variations and Starling effect of epidural space.

PMID- 11306747
TI  - Circulating levels of interleukin-8 and vascular endothelial growth factor in
      patients with carotid stenosis.
AB  - Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) are important
      factors that induce the migration and proliferation of endothelial cells,
      increase the vascular permeability, and the modulate chemotaxis of monocytes.
      These molecules have been found in human atherosclerotic plaques. However, it is
      not clear whether the circulating levels of IL-8 and VEGF correlate with the
      extents of carotid stenosis. In this study, we investigated the relationship
      between circulating levels of IL-8 as well as VEGF and the extents of carotid
      stenosis. Sera from 41 patients with carotid stenosis were assessed for
      concentrations of IL-8 and VEGF by enzyme-linked immunosorbent assay. The degree
      of stenosis of extracranial carotid artery was calibrated by carotid B- mode
      ultrasonography. The serum concentration of IL-8 (r = -0.04733, p > 0.05) was not
      correlated with the degree of stenosis. However, the serum concentration of VEGF
      (r = 0.4974, p < 0.01) was significantly correlated with the degree of carotid
      stenosis. These findings suggest that increased serum level of VEGF might be a
      marker for higher degree of stenosis of extracranial carotid artery.

PMID- 11306748
TI  - Distal anterior cerebral artery aneurysms: clinical features and surgical
      outcome.
AB  - Aneurysms of the distal anterior cerebral artery (DACA) are rare and their
      surgical treatments present some unique difficulties from a technical standpoint.
      In this report, we presented our experiences of cases with DACA aneurysms, and
      analyzed the clinical features and prognostic factors affecting the final
      outcomes. Among 770 cases of intracranial aneurysms operated from 1990 to 1998,
      19 cases of DACA aneurysms (2.5%) were studied retrospectively. The
      characteristic findings were female preponderance (M:F = 1:2.8), common multiple
      aneurysms (57.9%), and frequent intracerebral hemorrhage (ICH) on initial brain
      CT scan (42.1%). All patients were operated via interhemispheric approach.
      Intraoperative aneurysmal rupture was developed only in 3 cases (15.8%), and had
      no relationship with the final outcome Fifteen out of 19 patients (78.9%) showed
      favorable outcome with a mortality rate of 5.3%. The follow-up data suggest that
      the initial ICH on brain CT scan portend a poor prognosis.

PMID- 11306749
TI  - CNS cholinergic innervation to the hippocampus in the rat using pseudorabies
      virus as a neurotracer.
AB  - The hippocampus is a central area of the memory-related neural system. Combined
      immunohistochemistry against choline acetyl transferase and retrograde
      transneuronal labelling of the pseudorabies virus were used to identify
      cholinergic neurons in the central nervous system projecting to the hippocampal
      formation of the rat. Five to ten microL of Bartha strain of pseudorabies virus
      were injected into the dentate gyrus, CA1 and CA3 of the hippocampus of 20
      Sprague Dawley rats using stereotaxic instrument. Forty eight to 96 hr after the
      injection, the brains were removed and the tissue sections were processed for
      double immunofluorescence procedure using polyclonal antibodies against
      pseudorabies virus or choline acetyl transferase. The double labelled neurons
      were distributed at several different nuclei and the labelling patterns of three
      different areas of the hippocampus were similar. These data suggests that the
      cholinergic innervation to the hippocampus were distributed in a transsynaptic
      manner throughout the whole brain area.

PMID- 11306750
TI  - Cytologic and histologic correlation of atypical glandular cells of undetermined
      significance.
AB  - To determine the cytologic and histologic correlation of atypical glandular cells
      of undetermined significance (AGUS) in Papanicolaou smears, a cytology file from
      January 1998 to May 1999 was reviewed. Surgical pathology files were searched to
      determine which patients received subsequent biopsies. One hundred thirty-two
      patients with AGUS were identified. Corresponding biopsies were available for 82
      of these cases. AGUS has been sub-classified into 3 subtypes: 1) AGUS, favor
      reactive; 2) AGUS, not otherwise specified; and 3) AGUS, favor neoplasia. The
      pathologic findings for the respective Papanicolaou smears with the diagnosis of
      each subtype of AGUS through the follow-up period were as follows: benign lesions
      in 56.1%, 0%, and 1.2%; squamous intraepithelial lesions 2.4%, 0%, and 1.2%;
      glandular intraepithelial lesions 0%, 0%, and 17.1%; endometrial simple
      hyperplasia 1.2%, 0%, and 0%; and carcinoma 0%, 9.8%, and 11%, respectively. In
      conclusion, AGUS, on cervical cytologic screening, was correlated with
      significant pathologic findings in 41.5% of the patients (37.8% with preinvasive
      or invasive glandular lesions and 9.6% with combined squamous intraepithelial
      lesions). It is thought that intensive follow-up studies, including colposcopy,
      cervical biopsy, and curettage, should be recommended for complete evaluation of
      AGUS.

PMID- 11306751
TI  - Malignant solitary fibrous tumor of the pleura causing recurrent hypoglycemia;
      immunohistochemical stain of insulin-like growth factor i receptor in three
      cases.
AB  - We present three cases of malignant solitary fibrous tumors of the pleura (SFTP)
      that produced recurrent hypoglycemia. Removal of the tumors produced
      normoglycemia. The tumors were well circumscribed and lobulated, and consisted of
      firm masses weighing 1,150 g to 1,450 g with the greatest diameter of 15 to 20
      cm. The tumors were composed of spindle cells in fascicles or in a haphazard
      arrangement and were highly cellular and mitotically active (3-8 mitoses/10 high
      power fields), showing histologically malignant features. Ultrastructurally,
      fibroblastic features of the tumor cells were present. Insulin-like growth
      factors (IGF) have been implicated in the presentation of hypoglycemia. The serum
      insulin and C-peptide levels were not elevated. Serum IGF-I levels were also low
      with values of 97.4, 157.1 and 51.9 ng/mL (ref. 125-317 ng/mL), respectively.
      However, tumor cells were strongly positive for IGF-I receptor on
      immunohistochemical analysis. It is tempting to speculate that IGF-I contributes
      to the hypoglycemia, even though the circulating levels were low.

PMID- 11306752
TI  - A case of localized persistent interstitial pulmonary emphysema.
AB  - Interstitial pulmonary emphysema is a well-documented complication of assisted
      mechanical ventilation in premature infants with respiratory distress syndrome.
      Localized persistent interstitial pulmonary emphysema (LPIPE) confined to a
      single lobe was incidentally presented in a 4-day-old female infant. This patient
      was a normal full-term baby with no respiratory distress symptom and no
      experience of assisted mechanical ventilation. Chest radiograph showed
      radiolucent area in right lower lobe zone, which needed differential diagnosis
      from other congenital lesions such as congenital cystic adenomatoid malformation
      and congenital lobar emphysema. CT scan showed irregular-shaped air cystic spaces
      and pathologically, cystic walls primarily consisted of compressed lung
      parenchyma and loose connective tissue intermittently lined by multinucleated
      foreign body giant cells.

PMID- 11306753
TI  - Gastric lymphangioma.
AB  - Gastric lymphangioma is a rare benign gastric tumor composed of unilocular or
      multilocular lymphatic spaces. On gastrofiberscopy a submucosal tumor covered
      with smooth transparent normal mucosa is revealed in the stomach with or without
      a stalk. Endoscopic ultrasonography has become an indispensable tool for
      differentiating these gastric tumors. Treatment of lymphangioma depends on its
      size, location, and presence of complications. Endoscopic resection is safe and
      easy and plays an important role in confirming the diagnosis and treatment of the
      tumors especially of small-sized ones. We report a case of gastric lymphangioma
      in a 68-yr-old woman who presented with nausea and vague epigastric discomfort
      for two months. She was diagnosed by gastrofiberscopy with endoscopic
      ultrasonography and treated successfully with endoscopic resection by strip
      biopsy method.

PMID- 11306754
TI  - Juxtaglomerular cell tumor of the kidney: a case report.
AB  - We report a case of renin-secreting juxtaglomerular cell tumor which developed in
      a hypertensive 47-yr-old Korean man. Presumptive clinical diagnosis was made
      before surgery based on the high level of plasma renin and the radiologic
      evidence of renal mass. Grossly, a round, bulging, well-encapsulated mass of 3 x
      3 cm was located in the mid-portion of the right kidney. On microscopic
      examination, the tumor was composed of ovoid to polyhedral cells with bland
      nuclei, indistinct nucleoli and light eosinophilic cytoplasm. The immunostaining
      for renin showed strong positivity in the cytoplasm of tumor cells. The
      characteristic rhomboid shaped renin protogranules were observed in
      ultrastructural analysis.

PMID- 11306755
TI  - Mucinous cystadenoma coexisting with stromal tumor with minor sex-cord elements
      of the ovary: a case report.
AB  - Mucinous neoplasms occur rarely in association with cystic teratoma, Sertoli
      Leydig cell tumor, granulosa cell tumor or carcinoid tumor. Several cases of an
      ovarian stromal tumor with minor sex-cord elements have been reported in the
      literatures. However, there has been no report about an ovarian mucinous neoplasm
      coexisting with a stromal tumor with sex-cord elements yet. We report a case of
      an ovarian neoplasm composed of both mucinous cystadenoma and stromal tumor with
      minor sex-cord elements in a 58-yr-old female. The ovary including the mass
      measured 5 cm in size. On section, it revealed an unilocular cyst (4.5 cm in
      diameter) filled with mucinous fluid. There was a round, yellow, solid nodule,
      1.5 cm in diameter within the wall. Microscopically, the cyst was lined by a
      single layer of endocervical mucinous epithelium and the nodule was composed of
      spindle cells showing an intersecting and whorled arrangement. There were cell
      nests showing polygonal shape with abundant cytoplasm among the spindle cells.
      They showed immunoreactivity for inhibin and did not have any connection with the
      adjacent mucinous epithelium. Therefore, we interpret the mucinous cystadenoma as
      having arisen de novo.

PMID- 11306756
TI  - Hemangioendothelioma of the sphenoid bone: a case report.
AB  - Hemangioendothelioma is borderline or intermediate type of vascular neoplasm.
      Hemangioendothelioma is rare lesion that constitutes less than 0.5% of the
      malignant tumors of bone. We present a case of low-grade hemagioendothelioma of
      the skull in a 29-yr-old woman. She had pain, diplopia and exophthalmos of the
      left eye. Radiographic images showed a relatively well-demarcated, expansile
      osteolytic lesion with irregularly thickened trabeculae and calcifications in the
      left greater wing of sphenoid bone. Histologically, the tumor was an infiltrative
      vasoformative lesion. The vessels are generally well-formed with open or
      compressed lumina surrounded by endothelial cells showing mild atypia. It lacked
      frequent mitotic figures and severe atypia. Although excessive bleeding occurred
      during the operation, the mass was totally resected. Postoperative radiation was
      not necessary. She is free of disease and well 6 months postoperatively.

PMID- 11306757
TI  - Multiple intracranial aneurysms associated with branchio-oto-dysplasia.
AB  - Branchio-oto-dysplasia is characterized by abnormalities of embryonic branchial
      arch system and deafness inherited as autosomal dominant with variable gene
      expression. We present a rare case of multiple intracranial aneurysms associated
      with branchio-oto-dysplasia. A 40-yr-old man with severe headache presented as
      spontaneous subarachnoid hemorrhage on brain computed tomographic scan. The
      patient also manifested clinical features of branchio-oto-dysplasia and right
      hemifacial hypoplasia. Carotid angiogram confirmed an aneurysm in the anterior
      communicating artery. Intraoperative findings demonstrated multiple aneurysms in
      the anterior communicating artery and in the left posterior communicating artery,
      which were clipped successfully. Postoperative course was uneventful. This
      condition has not been reported previously. We also reviewed literatures to
      discuss whether the intracranial aneurysm was as a coincidental finding or a part
      of this malformation.

PMID- 11306758
TI  - A case of retroperitoneal lipoleiomyoma.
AB  - We report a case of lipoleiomyoma which arose in retroperitoneum and presented
      with progressively distended abdomen in a 56-yr-old woman. The tumor was well
      encapsulated and consisted of two components, benign smooth muscle cells and
      mature adipose tissue without any atypia. It is likely to be mistaken as
      extrarenal angiomyolipoma, well-differentiated liposarcoma and leiomyoma with
      fatty change. We review the histologic characteristics of previously reported
      myolipoma and describe essential points of differential diagnosis.

PMID- 11306759
TI  - Imaging of acute stroke.
AB  - The utility of diagnostic imaging during the critical first few hours after
      stroke onset has many important applications. First and foremost, imaging
      technologies that can reliably detect and quantify the location of acute stroke
      will greatly enhance the clinician's ability to accurately diagnose individual
      stroke patients. Secondly, if imaging technology could provide information about
      the likely severity of the ischemic injury, patient prognosis and management
      would be enhanced. The possibility of potentially distinguishing severely injured
      and likely irreversible ischemic brain tissue from ischemic tissue likely not yet
      irreversibly injured may soon be attainable. The ability of imaging technology to
      reliably distinguish the status of focally ischemic brain will presumably
      dramatically impact upon patient management. This information, along with the
      data about the severity and extent of blood flow and tissue perfusion
      abnormalities, will help acute stroke care evolve beyond rigid time windows to
      individualized, pathophysiologically based treatment decisions. Not only will
      decisions to treat or not be made based upon imaging-derived status, but also the
      most appropriate type of therapy to be employed, i.e. thrombolysis,
      neuroprotection, therapy to reduce secondary reperfusion-related injury or
      combinations of these modalities. In this brief and necessarily incomplete
      overview of acute stroke imaging, the focus will be on new developments in CT and
      MRI.

PMID- 11306760
TI  - Early diagnosis of hemorrhagic transformation: diffusion/perfusion-weighted MRI
      versus CT scan.
AB  - Standard magnetic resonance imaging (MRI) techniques failed to image adequately
      acute hemorrhagic transformation (HT). Therefore, computed tomography (CT) is
      still needed to exclude intracerebral hemorrhage. New MRI techniques such as
      diffusion- and perfusion-weighted imaging (DWI and PWI) may improve the early
      detection of HT. The utility of this approach requires a direct comparison of the
      sensitivity of CT with these MRI techniques. METHODS: Nine patients experienced
      an acute carotid artery territory ischemic stroke diagnosed on a first CT
      performed 3.8 +/- 2 h after the onset of stroke. They underwent a second CT 12 +/
      4 h after the onset of stroke, followed 35 +/- 10 min later by an MRI protocol
      including: (1) an axial isotropic DWI SE echo-planar imaging (EPI) sequence; (2)
      time of flight MR angiography (TOF MRA); (3) PWI with an axial T(2)*-weighted
      gradient echo EPI sequence using 20 ml gadolinium contrast agent (Gd-DTPA); HT
      was characterized on DWI SE EPI as a heterogeneous area of signal loss within the
      ischemic area; (4) at day 7, CT was also performed in all patients who had an
      early suspicion of bleeding according to MRI. RESULTS: An HT was detected
      exclusively with CT in 1 out of 9 patients, while an MRI pattern of HT was found
      in 6 out of 9 patients. In 5 of these 6 patients, the CT scan did not show an
      obvious pattern of HT. Day 7 CT confirmed HT in all patients who had early
      suspicion of bleeding according to DWI criteria. CONCLUSION: This study suggests
      that new MRI techniques may allow an early detection of HT, thus improving the
      management of stroke.

PMID- 11306761
TI  - Scattered brain infarct pattern on diffusion-weighted magnetic resonance imaging
      in patients with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Infarct patterns on brain imaging contribute to the
      etiologic classification of ischemic stroke. However, the association of specific
      subtypes of infarcts and etiologic mechanisms is often weak, and acute lesions
      are frequently missed on initial computed tomography (CT). Diffusion-weighted
      imaging (DWI) is superior in visualizing acute ischemic lesions as compared to CT
      and conventional magnetic resonance imaging (MRI). In our prospective study, we
      addressed the question whether a distinct pattern of infarction on DWI is
      associated with infarct etiology and clinical outcome. METHODS: Sixty-two
      patients with clinical signs of acute ischemic stroke and negative acute CT upon
      admission underwent DWI within 10 days after the ictus. Neurological status was
      documented using the NIH stroke scale. A scattered lesion pattern was defined by
      at least 2 separate hyperintense DWI lesions within the territory of one of the
      major cerebral arteries. Ischemic lesions were defined as acute if the region was
      demarcated strongly hyperintense in all DW images, and if the apparent diffusion
      coefficient was below normal. RESULTS: In 32 patients, DWI revealed a scattered
      lesion pattern, while in 30 patients a single acute lesion was detected. In
      patients with scattered lesions, potential arterial or cardiac embolic sources
      were detected in 26 patients (81.3%), as compared to 5 patients (16.6%) in the
      group with single lesions (chi(2) test, p < 0.0001). The neurological status of
      patients with scattered lesions improved significantly more than among patients
      with single lesions (Mann-Whitney test, p < 0.0003). CONCLUSION: A scattered
      lesion pattern on DWI in patients with acute brain infarction and negative
      initial CT scan is associated with an embolic etiology and may indicate a
      favorable clinical outcome.

PMID- 11306762
TI  - Linear hyperintensity objects on magnetic resonance imaging related to
      hypertension.
AB  - Linear hyperintensity lesions, which are sometimes recognized in the cerebral
      white matter on T(2)-weighted magnetic resonance (MR) images, have never been
      studied from the clinical viewpoint. We refer to these lesions as linear
      hyperintensity objects (LHOs) and have investigated them quantitatively. Twenty
      six consecutive patients underwent routine 1.5-Tesla MR imaging. LHOs were found
      in 24 patients. We measured the width and number of LHOs at the upper corona
      radiata level on T(2)-weighted images (repetition time: 4,500.0 ms, echo time:
      96.0 ms) using a scale loupe. The diameters were significantly correlated with
      the stages of hypertension (WHO classification). The LHOs may associated with the
      dilated perivascular spaces of cortical medullary arteries and may become an
      indicator for hypertensive small vessel disease.

PMID- 11306763
TI  - Diffusion-weighted mr in cerebral venous thrombosis.
AB  - The diagnosis of cerebral venous thrombosis is often difficult both clinically
      and radiologically and until now there is no method available to predict if brain
      lesions, detected clinically and using conventional brain imaging methods, may
      lead to full recovery, as expected in vasogenic edema or ischemic infarcts and
      even a hematoma. New fast neuroimaging techniques such as diffusion-weighted
      imaging (DWI) are sensitive to different reasons of changes in local tissular
      water concentration thus giving further insight into the pathophysiological
      mechanism as well as prognosis of cerebral venous thrombosis. We report the cases
      of 18 consecutive patients with a diagnosis of cerebral venous thrombosis based
      on clinical and imaging criteria. All patients underwent magnetic resonance
      imaging (MRI) of the brain, which comprised isotropic diffusion-weighted MR.
      Diffusion-weighted MRI showed positive findings in 17/18 cases. In 7 cases the
      clot could be directly visualized as an area of hyperintensity in the affected
      vein on DWI. In 7 cases DWI showed areas of signal loss corresponding to
      hematomas. In 6 cases DWI showed changes in signal intensity that were more
      subtle. In 4 cases of superficial venous thrombosis, there were areas of
      decreased ADC values (0.65-0.79 x 10(-3) mm(2)/s) whereas in 2 cases of deep
      venous thrombosis, increased DWI intensities could be found that corresponded to
      both an increase and a decrease in ADC, corresponding to a coexistence of
      cytotoxic and vasogenic edemas. Diffusion-weighted MRI can demonstrate directly
      the presence of an intravenous clot in a select number of patients. It can also
      demonstrate early ischemic changes, and can differentiate conventional T2
      weighted MR areas of cytotoxic from vasogenic edema.

PMID- 11306764
TI  - Cerebral vein and dural sinus thrombosis in Portugal: 1980-1998.
AB  - There is insufficient information on the prognosis and safety of anticoagulation
      in acute cerebral vein and dural sinus thrombosis (CVDST). To describe the
      clinical aspects and medical management of CVDST in Portuguese hospitals, to
      evaluate the safety of anticoagulation in this setting, and to identify subgroups
      of CVDST patients with different prognoses, we registered symptomatic CVDST
      patients admitted to Portuguese hospitals since 1980. Cases were collected from
      file review up to 6/95 and from consecutively admitted patients from 6/95 to
      6/98. One hundred and forty-two patients were included from 20 centers (51
      retrospectively and 91 prospectively). One hundred and twelve patients (79%) were
      anticoagulated. There were only 6 new intracranial hemorrhages (4 in
      anticoagulated patients) and 2 systemic hemorrhages. Nine (6%) patients died. At
      discharge, 96 (68%), had recovered completely and only 6 (4%) were dependent
      (Rankin > or = 3). Significant multivariate predictors of death/dependency were
      central nervous system infection as a predisposing cause (odds ratio, OR = 15.4;
      95% confidence interval CI = 111-1.1), encephalopathy on admission (OR = 5.2; 95%
      CI = 18.7-1.5) and hemorrhage on admission CT/MR (OR = 3.6; 95% CI = 12.9-1).
      Significant predictors of complete recovery were no encephalopathy on admission
      (OR = 5; 95% CI = 12.5-2.1), age < 45 years (OR = 3.8; 95% CI = 9.2-1.6) and
      anticoagulation (OR = 3.8; 95% CI = 9.6-1.5). It is possible to identify CVDST
      patients with potential bad or good prognosis in the acute phase. Anticoagulation
      was safe and a predictor of complete recovery in acute CVDST.

PMID- 11306765
TI  - Can we predict poor outcome at presentation in patients with lobar hemorrhage?
AB  - OBJECTIVE: Supratentorial lobar hemorrhage can be devastating. Outcome prediction
      at presentation is important in triage and management decisions as well as
      appropriate resource utilization. We performed a decision tree analysis combining
      clinical and CT scan features to predict poor and hopeless outcome at initial
      presentation in patients with lobar hemorrhage. METHODS: We analyzed 81 patients
      with spontaneous lobar hemorrhage presenting within 48 hours of initial
      neurologic symptoms. In the first analysis, poor outcome was defined as Glasgow
      outcome score (GOS) of 1 (death), 2 (vegetative state) or 3 (dependence) at
      discharge. A second analysis was based on worst possible outcome (GOS 1-2).
      Binary recursive partitioning was fitted in a model, and odds ratios with 95%
      confidence intervals (CI) were calculated. RESULTS: Lobes involved were temporal
      (36%), parietal (33%), frontal (25%) and occipital (6%). Seventy-three percent of
      patients presented less than 17 h after initial ictus. The probability of poor
      outcome was 97% (CI 85-100%) in patients with hemorrhage greater than 40 cm(3).
      In the subset of patients with a volume less than 40 cm(3), time interval from
      ictus to presentation (< 17 h) together with a Glasgow coma score (GCS) less than
      or equal to 13 predicted poor outcome. Eighty-five percent (CI 42-99%) of those
      presenting early with GCS less than or equal to 13 had a poor outcome. In the
      second analysis, all patients with GCS less than or equal to 12 and septum
      pellucidum shift > 6 mm had GOS of 1 or 2 (CI 72-100%). CONCLUSION: Poor outcome
      in patients with lobar hemorrhage is associated with a hemorrhage size of more
      than 40 cm(3), GCS less than or equal to 13, but also dependent on time interval
      between ictus and presentation. This is consistent with prior studies
      demonstrating deterioration from enlargement may occur when patients present
      early on. Stupor and septum pellucidum shift greater than 6 mm on CT scan at
      presentation predict a hopeless outcome in conservatively treated patients.
      Ninety-one percent of patients were treated medically, thus these outcomes are
      largely a reflection of the natural history of spontaneous lobar hemorrhage.
      These signs may influence triage and management decisions.

PMID- 11306766
TI  - Treatment of cerebellar hematoma in The Netherlands. A questionnaire survey.
AB  - A questionnaire was sent to Dutch neurosurgeons and neurologists in order to
      assess current management strategies for cerebellar hematoma. Seven patients were
      presented, using as determinants: size of hematoma, coma score, interval to
      clinical deterioration, hydrocephalus, comorbidity, anticoagulant treatment and
      age. Neurological management options were: no treatment, monitoring or referral
      for neurosurgery. Neurosurgical options were: no treatment, monitoring, hematoma
      evacuation, and/or external ventricular drainage. Ninety-seven of 161 (60%)
      neurologists, and 58 of 85 neurosurgeons (68%) responded. Only 20 respondents
      (13%) made use of a local guideline. Overall agreement was perfect in 1 case and
      moderate to high in the others, but chance-adjusted agreement (kappa) between
      pairs of neurologists and neurosurgeons who were matched for referral center was
      not statistically significant except in 1 case, a deeply comatose patient with a
      4-cm hematoma. In an alert, slightly ataxic patient with a large (4.5-cm)
      hematoma, 84 neurologists (88%) decided not to refer the patient. The estimated
      time for transfer between centers was of no influence on this decision. We
      conclude that the management of cerebrellar hematoma can be improved upon by
      encouraging the use of local guidelines, and by promoting early referral to a
      center with neurosurgical facilities.

PMID- 11306768
TI  - Acute phase predictors of subsequent psychosocial burden in carers of elderly
      stroke patients.
AB  - The objective was to describe the psychosocial burden experienced by informal
      carers of elderly stroke victims, and to identify its predictors among baseline
      characteristics of the patients. From a prospective study of 171 elderly stroke
      patients admitted to a geriatric ward for rehabilitation in the acute phase, 68
      patients living at home with a primary caregiver were identified 6 months after
      the stroke. At baseline, all the patients were assessed with respect to motor
      function, cognitive function, global handicap and activities of daily living, and
      after 6 months the caregivers were assessed, using the Relatives' Stress Scale.
      According to this, the most frequent impacts were worries that an accident might
      befall their relatives, that they had to reorganise their household routines and
      further, that their social life and ability to take holidays had been reduced.
      Impaired cognitive function was the only baseline patient characteristic that
      predicted a subsequent psychosocial burden on the carer. Special attention should
      be paid to elderly stroke patients initially assessed with impaired cognitive
      function and their caregivers.

PMID- 11306767
TI  - Intracranial hemorrhage and oral anticoagulant treatment.
AB  - OBJECTIVE: To detect risk factors for intracranial hemorrhage (ICH) in patients
      with long-term oral anticoagulant and to identify clinical or radiological data
      specific of anticoagulant-related ICH. METHODS AND PATIENTS: Three groups of
      patients were included. Group 1 represents patients who were admitted because of
      anticoagulant-related ICH between January 1984 and February 1996. All patients
      underwent CT scan. Clinical data, anticoagulation parameters, location and volume
      of the ICH, treatment and the 30-days in-hospital mortality were analyzed. Group
      2 consisted of patients selected at random among all patients with spontaneous
      ICH admitted to our department during the same period of time. Patients without
      ICH, but regularly taking oral anticoagulants constituted group 3. RESULTS:
      Seventy-nine patients with anticoagulant-related ICH were compared to 127
      patients with spontaneous ICH. The volume of supratentorial ICH was greater in
      group 1 of patients and was correlated with a worse prognosis. Comparison of
      group 1 with group 3 (212 controls) demonstrated that length of anticoagulation,
      prothrombin time or excessive anticoagulation, prior cerebral infarct and use of
      acenocoumarol, but not age or indication of anticoagulant, were significant risk
      factors for ICH in multivariate analysis. CONCLUSIONS: The results emphasize that
      anticoagulant-related ICH are not clinically different from spontaneous ICH
      except for volume of bleeding, and that frequent and careful coagulation
      monitoring is needed, especially during the first year in order to decrease the
      risk of ICH.

PMID- 11306769
TI  - Potentially reversible factors during the very acute phase of stroke and their
      impact on the prognosis: is there a large therapeutic potential to be explored?
AB  - In the Copenhagen Stroke Study, we evaluated the combined impact on stroke
      outcome of potentially treatable factors such as acute body temperature, blood
      glucose, and stroke in progression. The patients were stratified into two groups:
      (1) patients with 'good' prognostic parameters (body temperature on admission <
      or = 37.0 degrees C and plasma glucose on admission < or = 6.5 mmol/l and who did
      not develop stroke in progression) and (2) patients with correspondingly 'poor'
      prognostic parameters. A poor outcome was observed in 4% of the patients with
      good prognostic parameters versus in 49% of the patients with poor prognostic
      parameters (p < 0.01). In the multivariate analysis which also included stroke
      severity, blood glucose contributed significantly to poor outcome with an odds
      ratio (OR) of 1.2/1.0 mmol/l increase, body temperature with an OR of 2.2/1
      degrees C increase, and stroke in progression with an OR of 2.9. However, the
      combined effect of all three factors was more than additive with an OR of 10.0
      (95% CI 1.5-56; p < 0.01). We have shown that in human stroke a strong and more
      than additive association exists between potentially reversible parameters and
      outcome. Intervention trials can prove whether these marked relations are causal.

PMID- 11306770
TI  - Intravenous thrombolysis in proximal middle cerebral artery occlusion.
AB  - Subgroup analyses of data from an open-label study of intravenous recombinant
      tissue plasminogen activator (rt-PA) administered to stroke patients were
      performed. Clinical outcome and incidence of intracranial hemorrhage were
      evaluated in 20 patients diagnosed by transcranial Doppler ultrasound as having
      proximal middle cerebral artery (MCA) occlusion. Additionally early infarct signs
      and size of final infarction were assessed. A favorable outcome (mRS 0-2) was
      seen in 30% of all patients. The incidence of symptomatic intracranial hematoma
      (10%) in patients with proximal MCA occlusion was higher than the overall
      hemorrhage rate of intravenous rt-PA treatment, but comparable to the data on
      intra-arterial thrombolysis in this stroke subgroup. All patients except 1
      developed ischemic infarction in the MCA territory. Intravenous rt-PA treatment
      within 3 h may also be effective in patients with proximal MCA occlusion. The
      risk of intracerebral hematoma does not seem to be greater than in intra-arterial
      thrombolysis.

PMID- 11306771
TI  - Prestroke dementia.
AB  - OBJECTIVE: To determine the frequency, associated factors and outcome of dementia
      previous to a stroke. DESIGN: Cross-sectional study of a cohort of 324
      consecutive unselected stroke patients (mean age 70.9 years, range 20-98; 255
      ischaemic, 46 haemorrhagic and 25 indefinite). METHODS: Cognitive and functional
      status prior to stroke were assessed by means of an interview to a relative, a
      short version of the Informant Questionnaire on Cognitive Decline in the Elderly
      and the Barthel Index. The DSM-III-R criteria were used to establish the
      diagnosis of prestroke dementia. Clinical and CT features of patients with and
      without prestroke dementia were compared. RESULTS: Forty-nine patients (15%) were
      demented before stroke; they were significantly older, less well educated, they
      had more frequently female gender, prior cerebrovascular disease, cerebral and
      medial temporal lobe atrophy and leukoaraiosis in the CT scan, and they had a
      higher mortality rate. Female sex (OR 3.7, CI 95% 1.2-12), low education (OR 2.1,
      CI 95% 1.1-4.2), previous stroke (OR 3.6, CI 95% 1.2-11), and cerebral atrophy
      (OR 3.8, CI 95% 1.7-8.3) were independently associated with prestroke dementia in
      the logistic regression analysis. CONCLUSIONS: Fifteen percent of stroke patients
      have prestroke dementia and they have a worse outcome. Factors associated with
      prestroke dementia are reminiscent both of degenerative and vascular brain
      pathology.

PMID- 11306772
TI  - Longitudinal study of blood pressure and stroke in over 37,000 People in China.
AB  - As part of a longitudinal study performed in urban China, 37,655 subjects were
      evaluated for stroke risk factors, including having their blood pressure measured
      in a standard fashion. The cohort was followed for 3.5 years during which time
      427 subjects experienced incident strokes--221 ischemic, 203 hemorrhagic, and 3
      undefined. Both systolic and diastolic blood pressure were significantly related
      to risk of stroke and stroke type. Associations were stronger for systolic than
      diastolic blood pressure. These results emphasize the importance of systolic
      blood pressure, as opposed to diastolic, as a risk factor for stroke. In this
      study, the risk of stroke is increased by about 25% with each 10 mm Hg increase
      in systolic blood pressure.

PMID- 11306773
TI  - Blood pressure variability in Binswanger's disease and isolated lacunar
      infarction.
AB  - To determine whether blood pressure (BP) variability is increased in hypertensive
      patients with Binswanger's disease (BD), we studied two samples of consecutive
      treated hypertensive patients: (1) 11 with BD (mean age 71.3 +/- 5.2 years); (2)
      16 with lacunar infarction (mean age 65.2 +/- 8.3 years) without cognitive
      impairment. An averaged baseline office BP was obtained for 3 consecutive weeks.
      Ambulatory BP monitoring was then carried out to obtain the averaged mean
      systolic (SBP) and diastolic BP, and BP variability was defined as the standard
      deviation of consecutive BP values. RESULTS: Diurnal SBP variability was
      significantly increased in the BD group (p = 0.04). However, with the analysis of
      covariance for age and baseline office BP, the difference was no longer
      significant (p = 0.17 and p = 0.09, respectively). We conclude that increased BP
      variability in BD patients is probably due to older age and increased baseline
      office BP. Increased BP variability may be a risk factor for small-vessel
      disease, but not for cognitive impairment.

PMID- 11306774
TI  - Amantadine increases gait steadiness in frontal gait disorder due to subcortical
      vascular encephalopathy: a double-blind randomized placebo-controlled trial based
      on quantitative gait analysis.
AB  - In a randomized, double-blind placebo-controlled trial, 40 patients diagnosed as
      subcortical vascular encephalopathy (SVE) were given a daily dose of 500 ml i.v.
      amantadine vs. placebo for 5 days. Both groups were treated with physiotherapy on
      a daily basis. Quantitative gait analyses were performed at days 1 and 6 to
      evaluate gait steadiness from cadence, length of heel-to-toe movements,
      variability of centre of gravity (COG) and double support time. Both placebo- and
      amantadine-receiving patient groups showed mild improvement in gait parameters
      after study, which failed to show the superiority of amantadine, when comparing
      drug-induced changes between both groups. However, analysing the treatment
      effects from day 0 to day 6 in both groups separately, statistically significant
      changes could be found in the amantadine group for cadence, length of heel-to-toe
      movements in single support phase as well as for variability in double support
      phase and double support time (two-tailed paired t-test, p < 0.05), whereas in
      the placebo group, a statistically significant effect could only be seen for
      double support time (p < 0.05). In this small pilot study, amantadine tends to
      improve gait steadiness as evaluated by cadence, length of heel-to-toe movements
      in single support phase, variability in double support phase and double support
      time, in patients with moderate frontal gait disorder due to SVE. Improvements in
      the placebo group can be interpreted as physiotherapy effect, which improved gait
      steadiness slightly, however, this was statistically significant only for double
      support time.

PMID- 11306775
TI  - Carbon disulfide vasculopathy: a small vessel disease.
AB  - We present the clinical manifestations of 4 male patients with acute stroke-like
      symptoms and polyneuropathy after long-term exposure to carbon disulfide (CS2) in
      a viscose rayon plant. The ages of onset of polyneuropathy ranged from 42 to 45
      years with a duration of CS2 exposure between 6 and 21 years. The ages of onset
      of stroke were from 42 to 48 years. The risk factors for stroke including heart
      disease and diabetes were denied, except for smoking in 4, hyperlipidemia in 2
      and hypertension in 1. At the initial visit in 1992, only 2 patients developed
      sudden onset of hemiparesis suggesting a lacunar stroke before the diagnosis of
      CS2 intoxication. Brain computed tomography (CT) scans showed low-density lesions
      in the basal ganglia in 2 patients, cortical atrophy in 1 and normal in 1. Brain
      magnetic resonance image (MRI) study disclosed multiple lesions in the corona
      radiata and basal ganglia on T(2)-weighted images in 3 patients and cortical
      atrophy in 1. After the diagnosis, they left their jobs for a CS2-free
      environment, and improvement of the working conditions was noted. During 5 years
      follow-up period, another 2 patients also developed an acute episode of stroke
      with hemiparesis. Brain CT and/or MRI follow-up studies in these 2 patients
      revealed new lesions in the basal ganglia and corona radiata. Intriguingly, a
      patient with previous stroke also developed new lesions in the bilateral thalami
      and brainstem. Carotid Doppler scan, transcranial Doppler scan and/or cerebral
      angiography did not show any prominent stenosis or occlusion in the major
      intracranial large arteries. We conclude that encephalopathy may occur in
      patients after long-term CS2 exposure, probably due to impaired cerebral
      perfusion. The lesions tend to occur in the basal ganglia, corona radiata and
      even brainstem, particularly involving the small-sized vessels. In addition, the
      cerebral lesions may progress even after cessation of CS2 exposure. Therefore, we
      suggest that CS2 exposure may be a risk factor for stroke.

PMID- 11306776
TI  - Treatment of acute cerebral infarction with arginine esterase: a controlled study
      with heparin.
AB  - BACKGROUND AND PURPOSE: [corrected] There is no treatment proven to be of
      definitive benefit for ischemic stroke. Arginine esterase, a natural product from
      a snake venom, has been shown to reduce the serum fibrinogen level in human
      beings and may be useful in the treatment of ischemic stroke. In the present
      study, we compared the therapeutic effect of arginine esterase with that of
      heparin. SUBJECTS AND METHODS: We studied 50 consecutive patients with acute
      ischemic stroke who were admitted to the Asan Medical Center. We randomly
      administered either arginine esterase 0.005 unit/kg x 2 times/day or heparin
      (activated partial thromboplastin time 2-3 times of baseline value) intravenously
      for 7 days. Antiplatelets were administered afterwards in both groups. Blood
      fibrinogen, fibrinogen degradation product (FDP) and D-dimer levels were measured
      at 0, 6, 12, 18 h and 1, 2, 3, 7 and 30 days after the onset of stroke. NIH
      stroke scale was measured daily by 2 neurologists while Barthel index and Rankin
      scale were assessed at 7 days and 1 month after the onset of stroke by a research
      nurse. All these investigators were blinded to the therapeutic regimen each
      patient received. RESULTS: There were no significant differences in the mean age,
      gender proportion, stroke subtypes and baseline neurological severity between the
      two groups. One patient in the arginine esterase group died in an acute stage due
      to massive herniation and 1 in the heparin group underwent surgery for
      herniation. One (arginine esterase group) died of massive gastrointestinal
      bleeding due to previously unrecognized stomach cancer. Otherwise, no significant
      clinical and laboratory side effects were observed in both groups. In the
      arginine-esterase treated group, D-dimer and FDP levels were significantly (p <
      0.05) elevated, and fibrinogen level significantly (p < 0.05) decreased at 2-7
      days after the onset of stroke compared to the heparin-treated group. However,
      there was no significant difference in the neurological improvement reflected by
      NIH stroke scale, Barthel index and Rankin scale. CONCLUSION: Arginine esterase
      seems to be safe and has significant fibrinolytic effects when administered in
      the patients with acute ischemic stroke. However, in this preliminary study, it
      was not superior to heparin in terms of the improvement of neurological deficits.
      Further studies with larger doses and a larger number of subjects are required.

PMID- 11306777
TI  - Correlation of aphasia and/or neglect with cortical infarction in a subpopulation
      of RANTTAS.
AB  - Classically in neurology, aphasia and neglect were accepted as reliable markers
      of cortical lesions. The actual prognostic values of aphasia and neglect have yet
      to be formally tested. This analysis sought to determine the predictive accuracy
      of aphasia and/or neglect in acute stroke for cortical infarction. Data from the
      RANTTAS investigation of tirilazad mesylate in stroke patients were reanalyzed,
      comparing acute National Institutes of Health Stroke Scale (NIHSS) measures of
      aphasia and neglect to lesion location on day 7-10 CT scans. Correlations between
      the presence of aphasia and/or neglect and the presence of a cortical lesion were
      only in the moderate range, and positive predictive values were far from perfect,
      as would be expected. 'Subcortical' aphasia or neglect was more likely in large,
      subcortical lesions. Aphasia and neglect, as determined in the acute setting by
      the NIHSS, are only moderately associated with cortical infarct identified on
      follow-up CT scans. If selective neuroprotection is envisioned for acute stroke
      patients, more accurate markers of cortical infarction may be needed.

PMID- 11306779
TI  - Recovery of motor functions following hemiparetic stroke: a clinical and magnetic
      resonance-morphometric study.
AB  - Predictors for the degree of clinical recovery after stroke are still poorly
      defined. In this study we tried to assess the predictive value of clinical data
      and of lesion size for motor recovery after ischemic stroke. In 52 hemiparetic
      patients we monitored the course of clinical recovery by a dedicated score of
      sensorimotor hand function after their first stroke. The course of the lesion
      size was measured in proton density magnetic resonance images. Three groups of
      patients were identified. Patients with moderate initial motor deficit recovered
      almost completely within 9 days (17/17, group 1). From the patients with severe
      initial motor deficit, about equal numbers recovered (16/35, group 2) or remained
      severely impaired during the entire observation period of more than 6 months
      (19/35, group 3). There was no correlation between changes of lesion size and
      motor deficit. Logistic regression of probability of good clinical outcome on
      initial lesion size, initial motor score and subcortical versus cortical location
      of lesion showed that only the initial motor score was predictive (p = 0.006). A
      relative improvement of the initial motor score of about 20% in the first 4 weeks
      after stroke appeared to be a relevant cut point for good outcome. The data
      indicate that patients with mild initial motor deficits recover well, whereas
      severely affected patients may differ in outcome. Since lesion size was not
      correlated with outcome the amount of spared residual function appeared as major
      determinant for the capacity for motor recovery.

PMID- 11306778
TI  - The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on blood
      pressure and platelet function in acute stroke.
AB  - BACKGROUND AND PURPOSE: Hypertension is a common medical complication in acute
      stroke and is associated with a poor outcome. However, no large trials have
      assessed the effect of lowering blood pressure (BP) on outcome, and it remains
      unclear how BP should be managed in acute stroke. We assessed, in a double-blind
      randomised controlled trial, whether the nitric oxide (NO) donor glyceryl
      trinitrate (GTN, a known systemic and cerebral vasodilator), would lower BP and
      alter platelet function. METHODS: Thirty-seven patients with recent (< 5 days)
      ischaemic or haemorrhagic stroke were randomised by minimisation to 12 days of
      daily treatment with transdermal GTN or matching placebo patches. Twenty-four
      hour ambulatory BP was measured before and during GTN treatment at days 0, 1 and
      8. Platelet aggregation and expression of adhesion molecules were assessed at the
      same time points. Functional outcome (Rankin scale) and case fatality were
      assessed at 3 months. Analysis was by intention-to-treat. RESULTS: GTN
      significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8.
      The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was
      developing. Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1
      and 8, respectively, in the placebo group. GTN had no effect on heart rate, or
      platelet aggregation or expression of platelet adhesion molecules, including
      glycoproteins Ia, Ib, IIIa and P-selectin. Additionally, GTN did not alter case
      fatality or dependency, although the study was not powered for these outcomes.
      CONCLUSIONS: Transdermal GTN, an NO donor, lowered BP by 5-8%, a clinically
      significant and relevant, but not excessive, degree in patients with acute
      stroke. However, GTN had no effect on platelet aggregation or expression of
      adhesion molecules. Since NO donors increase cerebral blood flow in patients with
      acute ischaemic stroke, GTN may be an appropriate drug for testing the effect of
      lowering BP on functional outcome.

PMID- 11306780
TI  - Cerebral venous thrombosis in Hong Kong.

PMID- 11306781
TI  - Cerebrovascular disease associated with marijuana abuse: a case report.

PMID- 11306782
TI  - ESPRIT: protocol change.

PMID- 11306783
TI  - Pharmacokinetics of high-dose meropenem in adult cystic fibrosis patients.
AB  - Because patients with cystic fibrosis (CF) have pulmonary exacerbations secondary
      to multi-antibiotic-resistant Gram-negative bacilli, antibiotics, like meropenem,
      are often utilized. We studied the pharmacokinetics of meropenem (2 g i.v.
      administered every 8 h in clinically stable CF patients to determine if the
      recommended maximum doses could sustain adequate concentrations during the dosing
      interval. These pharmacokinetic data were similar to those obtained in non-CF
      populations. Using this regimen, concentrations of meropenem exceed the
      susceptibility breakpoint (4 microg/ml) for 50% of the dosing interval, and
      therefore provide optimization of the pharmacodynamic profile of the compound.

PMID- 11306784
TI  - In vitro and in vivo antibacterial activity and pharmacokinetics of SC-002 and
      its derivative, SC-004: new oral cephalosporins.
AB  - SC-002 is a novel oral cephalosporin possessing a unique thiadiazolylethenyl
      moiety at the 3 position. In the present study, it was the most active against
      gram-positive bacteria among oral cephalosporins such as cefdinir (CFDN),
      cefpodoxime, cefditoren and cefaclor (CCL). It was equal to or 16 times more
      active than CFDN against standard and clinical strains. In particular, against
      clinical isolates of Morganella morganii and Haemophilus influenzae, SC-002 was 8
      64 times more active than CFDN. The antibacterial activity of SC-002 against some
      beta-lactam-resistant strains was superior to that of CFDN. The in vivo
      antibacterial activity of SC-004, a pivaloyloxymethyl ester of SC-002, was 1.2-8
      times more protective against systemic infections due to Streptococcus
      pneumoniae, Escherichia coli and Klebsiella pneumoniae than that of CFDN. The
      therapeutic effects of SC-004 on experimental respiratory tract infections caused
      by S. pneumoniae or H. influenzae were superior to those of CFDN and CCL. SC-004
      showed higher and longer-lasting blood levels and higher urinary excretion in
      pharmacokinetics in mice.

PMID- 11306785
TI  - Improvement of water-soluble cephalosporin derivatives having antibacterial
      activity against methicillin-resistant Staphylococcus aureus.
AB  - We evaluated a series of novel cephem antibiotics, N-alkylpyridinium (alkyl
      group), N-carboxyethylpyridinium (carboxylic group), N-sulfoethylpyridinium
      (sulfonic group) and N-alkylquaternary ammonium salts (ammonioethyl group), N
      alkyl-aromatic-quaternary ammonium salts and N-alkyl-heterocyclic quaternary
      ammonium salts (cyclic group) as vinylthio pyridinium derivatives at the C-3
      position and hydroxyiminoaminothiazol at the C-7 position, for their activity
      against methicillin-resistant Staphylococcus aureus (MRSA) and their solubility,
      by measuring the minimum inhibitory concentrations (MICs) and the dissolving test
      in phosphate buffer. All tested compounds, except for the alkyl group, showed
      good solubility (>10%) in 1/15 M phosphate buffer (pH 7.2). The concentrations
      required to inhibit 80% of the bacterial strains (MIC80s) of the alkyl group,
      carboxylic group, sulfonic group, ammonioethyl group and cyclic group against
      MRSA were 1.56, 12.5-25, 6.25, 1.56 and 1.56 microg/ml, respectively. These
      results indicated that the ammonioethyl and cyclic groups yield the maximum anti
      MRSA and anti-Enterococcus faecalis activity, and also good water solubility.

PMID- 11306786
TI  - Isolation and antimicrobial susceptibility testing of fecal strains of the
      archaeon Methanobrevibacter smithii.
AB  - BACKGROUND: The archaeon Methanobrevibacter smithii is regarded as part of the
      indigenous microflora of the human intestine but may be connected with
      pathological conditions. The microbe is extremely oxygen intolerant and is not
      detectable by anaerobic culture techniques for bacteria. Accordingly, to date
      quantitative antimicrobial susceptibility data of human isolates are missing.
      METHODS: The anoxic Hungate technique and a three-step culture procedure using
      media supplemented with antibiotics were applied to isolate M. smithii from
      randomly selected human feces. The minimum inhibitory concentrations (MICs) of 15
      isolates and the reference strain DSM 861 were determined using a broth
      macrodilution test resembling the procedure for testing anaerobic bacteria.
      RESULTS: The 16 strains were highly resistant (MICs >64 mg/l) against penicillin
      G, cephalothin, vancomycin, streptomycin, gentamicin, ciprofloxacin, and
      clindamycin. Metronidazole inhibited the strains at MICs between 0.5 and 64 mg/l.
      CONCLUSIONS: Multiple-antibiotic-resistant Methanoarchaea occur in the human gut.
      They may be selected during therapy with common antibacterial agents and may be
      eliminated by the application of metronidazole.

PMID- 11306787
TI  - Effect of Sub-MICs of antibiotics on the hydrophobicity and production of acidic
      polysaccharide by Vibrio vulnificus.
AB  - BACKGROUND: Subinhibitory concentrations of antibiotics, which can occur in vivo,
      have been demonstrated to alter the production of bacterial virulence factors,
      including the capsule, or the interaction between microorganism and phagocyte by
      affecting surface hydrophobicity. METHODS: Using a microtiter assay system, the
      effect of subinhibitory concentrations of amikacin, gentamicin, cephalothin and
      doxycycline on the surface hydrophobicity and production of acidic polysaccharide
      by Vibrio vulnificus (8 human isolates, 8 environmental isolates) was determined.
      RESULTS: All four drugs, in a dose-dependent manner, caused alterations in
      adherence to polystyrene, a measure of surface hydrophobicity, and the production
      of acidic polysaccharides, as determined by Alcian blue staining. CONCLUSION: The
      changes in capsule production and surface hydrophobicity measured in response to
      sub-MICs of antibiotics appear to be independent variables.

PMID- 11306788
TI  - Circulating tumor necrosis factor-alpha production during the progression of rat
      endotoxic sepsis.
AB  - The endotoxin-mediated tumor necrosis factor-alpha (TNF-alpha) induction was
      investigated in a rat endotoxin septic shock model. Rats were challenged
      intravenously with lethal doses of endotoxin. Circulating endotoxin and TNF-alpha
      concentrations were measured over various times following endotoxin
      administration. A derivative of human immunoglobulin G, 5S-IgG, was administered
      at various times relative to endotoxin dosing to test its anti-endotoxin
      activity. Results showed that endotoxin challenge initiated substantial amounts
      of TNF-alpha release into the rat circulatory system leading to death. A temporal
      pattern of TNF-alpha increases following endotoxin administration was observed;
      the rat plasma TNF-alpha level rapidly increased 60 min after endotoxin
      injection, peaked around 120 min and returned to low levels by 240 min. A rapid
      clearance pattern of endotoxin was also observed in rats. 5S-IgG exhibited its
      moderate anti-endotoxin activity by partially suppressing the endotoxin-mediated
      TNF-alpha release and decreasing the overall mortality only when given before
      triggering of TNF-alpha induction. However, this inhibitory effect of 5S-IgG on
      endotoxin-mediated TNF-alpha release and the resultant protective effect against
      endotoxin lethality rapidly diminished when 5S-IgG was administered after the
      occurrence of TNF-alpha induction. Collectively, these results suggest that the
      timing of the anti-endotoxin treatment is critical in achieving its effectiveness
      and imply that the endotoxin levels after the onset of the cytokine cascade is of
      questionable significance.

PMID- 11306789
TI  - The antibacterial effects of ornidazole on primary molars with infected pulps.
AB  - The purpose of this study was to investigate the antibacterial effects of a short
      term topical application of ornidazole on anaerobic microorganisms. The
      antibacterial properties of such materials against organisms at infected primary
      root canals have not been well documented. Twenty infected primary molars in this
      study were treated using ornidazole (Biteral, Roche). The bacterial contents of
      the roots were collected with sterile paper points before the application.
      Freshly mixed ornidazole and sterile saline were placed into the root canals.
      After 1 week, the bacterial contents of the root canals were collected again.
      Microbiological analyses were made. Based on our results, it appears that the
      antibacterial activity of ornidazole caused significant changes in rates of
      microorganisms (94.53% reduction).

PMID- 11306790
TI  - Bacterial adhesiveness: effects of the SH metabolite of erdosteine (mucoactive
      drug) plus clarithromycin versus clarithromycin alone.
AB  - After metabolization, erdosteine (a mucoactive drug) produces an active
      metabolite (Met I) with an SH group that is capable of opening disulphide bonds,
      including those of pilin, a protein of bacterial fimbriae. This induces
      stereochemical conformational changes that interfere with the binding of
      bacterial adhesins (fimbriae) to receptors on eukaryotic cells. At subinhibitory
      concentrations, the macrolide clarithromycin inhibits the expression of adhesins
      on bacterial cell surfaces. The addition of 5 and 10 microg/ml of Met I to 1/8,
      1/16 and 1/32 MIC of clarithromycin potentiated the inhibition of Staphylococcus
      aureus adhesiveness to human mucosal cells in comparison with the antibiotic
      alone. This finding opens up a new possibility of interfering with bacterial
      adhesiveness and its resulting pathogenicity not only by using antibiotics but
      also by means of their combination with agents devoid of antibacterial activity.

PMID- 11306791
TI  - Prospective evaluation of the impact of amoxicillin, clarithromycin and their
      combination on human gastrointestinal colonization by Candida species.
AB  - BACKGROUND: Amoxicillin and clarithromycin have been used extensively for the
      eradication of Helicobacter pylori. However, no study has examined the impact of
      their combination on the Candida albicans concentration of the gastrointestinal
      (GI) tract. This is the first study examining and comparing directly the effect
      of amoxicillin, clarithromycin and their combination on the C. albicans
      concentration of the human GI tract. METHODS: Thirty-three adult patients (11 in
      each antibiotic group) were studied prospectively. Quantitative stool cultures
      for Candida were conducted at the beginning, the end and 1 week after the
      discontinuation of antibiotic treatment. RESULTS: All three regimens increased
      the GI colonization in patients by Candida. The combination of amoxicillin with
      clarithromycin caused the highest increase; however, this was not statistically
      significant. CONCLUSION: Amoxicillin and clarithromycin used either alone or in
      combination cause a small to moderate increase in GI colonization by Candida.
      Hence, these drugs could be safely used in patients at risk for candidiasis
      originating from the GI tract.

PMID- 11306792
TI  - Ceftriaxone for the treatment of febrile episodes in nonneutropenic patients with
      hematooncological disease or HIV infection: comparison of outpatient and
      inpatient care.
AB  - BACKGROUND: Patients with hematooncological disease or HIV infection and febrile
      episodes are usually treated in hospital with broad-spectrum antibiotics. The aim
      of this observational study was to assess the feasibility of ambulatory
      parenteral antibiotic therapy in hematooncological or HIV-infected patients with
      confirmed or suspected infection. METHODS: The results in an outpatient treatment
      group were compared with those obtained in a group initially treated in hospital.
      Data were gathered on 90 outpatients and 72 inpatients. The inclusion criteria
      were fever > or =37.5 degrees C with an identified focus of infection, fever > or
      =38.0 degrees C of suspected bacterial origin with no identified focus of
      infection, leukocytosis > or =9,000/microl or C-reactive protein elevation > or
      =10 mg/l. RESULTS: Eighty outpatients and 69 inpatients were evaluable. Treatment
      in the outpatient group was begun with ceftriaxone. This led to defervescence in
      87.5% of cases. The mean treatment duration was 7.1 days. Comparison of results
      in the outpatients with those initially hospitalized for treatment showed similar
      success rates. The mean hospital stay in the latter group was 12.9 days.
      CONCLUSIONS: Ceftriaxone represents an effective treatment for outpatient
      management of febrile episodes in patients with hematooncological disease or HIV
      infection. Outpatient treatment is more cost-effective than inpatient care.

PMID- 11306793
TI  - Treatment of febrile neutropenia with cefepime monotherapy.
AB  - BACKGROUND AND OBJECTIVE: The empirical administration of a broad-spectrum beta
      lactam antibiotic, either as monotherapy or in combination with an
      aminoglycoside, is an essential component of the initial management of patients
      with fever and severe neutropenia. Multiple antibiotics have been tested for this
      indication. Cefepime is a fourth-generation cephalosporin with in vitro activity
      against most gram-negative and many gram-positive bacteria. We have studied the
      use of this agent as monotherapy in this indication. METHODS: One hundred and
      twenty-six episodes of febrile neutropenia in 98 adults with hematological
      malignancies were treated with cefepime monotherapy. Cefepime was given at a dose
      of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while
      a microbiologically documented and clinically documented infection occurred in
      25% episodes each. Seventy-six (61%) episodes occurred after conventional
      chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation.
      RESULTS: Twelve episodes (10%) were not evaluable for response. Among the 114
      evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable)
      responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the
      initial sample and 39% of those evaluable), including 14 cases who developed
      breakthrough bacteremia during therapy. There were no deaths due to bacterial
      infection. At the end of all antibiotic therapy (final outcome) 69 episodes were
      cured only with monotherapy, 47 were cured with modification of therapy and 10
      patients died from an unrelated cause. The only variable that appeared to
      correlate with response to therapy was the duration of neutropenia, which was
      longer among patients who failed or developed breakthrough bacteremia than among
      those who responded to monotherapy. INTERPRETATION AND CONCLUSIONS: Initial
      empirical antibiotic therapy with cefepime as a single agent in patients with
      febrile neutropenia and a hematological malignancy is effective, but patients
      with prolonged neutropenia appear to be at higher risk for failure. However, with
      appropriate therapeutic changes the risk of dying from a bacterial infection is
      very low.

PMID- 11306794
TI  - Report and abstracts of the ninth international workshop on the molecular biology
      of human chromosome 21 and Down syndrome. Bar Harbor, Maine, USA. 23-26 September
      2000.

PMID- 11306795
TI  - Report and abstracts of the sixth international workshop on human chromosome 1
      mapping 2000. Iowa City, Iowa, USA. 30 September-3 October 2000.

PMID- 11306796
TI  - Report on the tenth international workshop on the identification of transcribed
      sequences 2000. Heidelberg, Germany, October 28-31, 2000.

PMID- 11306797
TI  - Improvement of FISH mapping resolution on combed DNA molecules by iterative
      constrained deconvolution: a quantitative study.
AB  - Image restoration approaches, such as digital deconvolution, are becoming widely
      used for improving the quality of microscopic images. However, no quantification
      of the gain in resolution of fluorescence images is available. We show that,
      after iterative constrained deconvolution, fluorescent cosmid signals appear to
      be 25% smaller, and 1.2-kb fragment signals on combed molecules faithfully
      display the expected length.

PMID- 11306798
TI  - Meiotic segregation analysis by FISH investigation of spermatozoa of a
      46,Y,der(X),t(X;Y)(qter-->p22::q11-->qter) carrier.
AB  - Chromosome analysis performed on a 30-year-old man revealed a
      46,Y,der(X),t(X;Y)(qter-->p22::q11-->qter) karyotype, confirmed by fluorescence
      in situ hybridization (FISH). The man was of short stature, and no mental
      retardation was noticed; genitalia and testes were normal, as were the patient's
      FSH, LH, and testosterone blood levels. Sperm analysis showed azoospermia at the
      time of the first sampling and severe oligozoospermia, with 125,000
      spermatozoa/milliliter, at the time of the second sampling. The sperm gonosomal
      complement of this patient and of a 46,XY donor were analyzed using multicolor
      FISH with X- and Y-chromosome probes. Our results clearly indicated that germinal
      cells carrying the translocation are able to complete the meiotic process by
      producing spermatozoa compatible with normal embryonic development, with more
      than 80% of the spermatozoa having either a Y chromosome or a der(X); however, a
      high level of spermatozoa with gonosomal disomies was observed. We also found a
      significant increase in the frequency of autosomal disomies in the carrier, which
      would suggest an interchromosomal effect. All previously reported cases in adult
      males were associated with azoospermia; testicular histological studies,
      performed in patients carrying the same X;Y translocation, showed spermatogenetic
      arrest after pachytene. To our knowledge, this is the first molecular analysis of
      the gonosomal complement in spermatozoa of men with a t(X;Y)(qter-->p22::q11-
      >qter).

PMID- 11306800
TI  - The human Y chromosome derives largely from a single autosomal region added to
      the sex chromosomes 80-130 million years ago.
AB  - Mapping of human X-borne genes in distantly related mammals has defined a
      conserved region shared by the X chromosome in all three extant mammalian groups,
      plus a region that was recently added to the eutherian X but is still autosomal
      in marsupials and monotremes. Using comparative mapping of human Y-borne genes,
      we now directly show that the eutherian Y is also composed of a conserved and an
      added region which contains most of the ubiquitously expressed Y-borne genes.
      Little of the ancient conserved region remains, and the human Y chromosome is
      largely derived from the added region.

PMID- 11306799
TI  - A mitotically stable marker chromosome negative for whole chromosome libraries,
      centromere probes and chromosome specific telomere regions: a novel class of
      supernumerary marker chromosome?
AB  - A two year-old child presented with mild developmental delay. On karyotype
      analysis, a supernumerary small marker chromosome (SMC) was found in all cells
      examined. This SMC was approximately the size of an isochromosome 18p, being
      symmetrical with a central constriction. C-banding and silver staining were
      negative and FISH with all chromosome-specific paints, centromere probes and
      telomere probes showed no hybridization to the SMC; telomere repeat sequences
      were however present on both arms. Comparative genomic hybridization showed no
      amplification of any chromosome region. Flow sorting of the SMC and reverse
      painting onto normal metaphase spreads showed no hybridization to any chromosome,
      whereas reverse painting onto the patient's own metaphases showed hybridization
      to the SMC only. This SMC may thus represent either a complex amplicon of
      different genomic regions, or a multifold amplification of a very small region,
      with a neocentromere comprising an active kinetochore but no alphoid DNA.
      Prognostic implications for the proband were difficult to assess due to the
      absence of reports of similar marker chromosomes in the literature.

PMID- 11306801
TI  - Genomic organization and promoter identification of ZNF146, a gene encoding a
      protein consisting solely of zinc finger domains.
AB  - The ZNF146 gene (alias OZF) encodes a protein consisting solely of ten zinc
      finger motifs. It is amplified and overexpressed in pancreatic carcinomas. To
      better understand the mechanisms controlling its expression, we have isolated the
      human ZNF146 gene and performed an initial assessment of its promoter activity.
      ZNF146 encompasses 25 kb of sequence and consists of four non-coding exons
      located upstream of a single coding exon. The sequence of proximal 1.4 kb of
      ZNF146 promoter has a high GC content, is devoid of a TATA box and contains
      several potential transcriptional elements. This region directs high-level
      expression of a transfected reporter construct in human cell lines. Analysis of a
      series of 5'-deletion constructs indicated that the first 80 bp upstream of the
      potential start site of transcription carry minimal promoter activity whereas the
      first 550 bp are required for maximal promoter activity.

PMID- 11306802
TI  - The functional myosin light chain kinase (MYLK) gene localizes with marker
      D3S3552 on human chromosome 3q21 in a >5-Mb yeast artificial chromosome region
      and is not linked to olfactory receptor genes.
AB  - The myosin light chain kinase (MYLK) gene is duplicated on human chromosome 3
      (3q13-->q21; 3p13), two sites known to contain olfactory receptor (OR) genes. The
      3p13 site contains a MYLK pseudogene (MYLKP) associated with a cluster of OR
      pseudogenes and therefore could have arisen from the duplication of a large
      region in 3q13-->q21. Here, we present the localization of the MYLK gene in a >5
      Mb region of the chromosome 3q21 integrated map. MYLK colocalizes with marker
      D3S3552. OR genes are absent from this region, suggesting that the 3p13
      duplicated region incurred further rearrangements during evolution.

PMID- 11306803
TI  - Chromosomal distribution, localization and expression of the human endogenous
      retrovirus ERV9.
AB  - ERV9 is a class I family of human endogenous retroviral sequences. Somatic cell
      hybrid genomic hybridization experiments using a mono-chromosomal panel indicate
      the presence of approximately 120 ERV9 loci in the human genome distributed on
      most chromosomes. Fluorescence in situ hybridization (FISH) using an ERV9 cDNA
      probe containing gag, pol and env sequences, verified this observation and a
      consistent signal was found at the chromosome region 11q13.3-->q13.5. By analysis
      of a panel of radiation hybrids, an ERV9 locus was mapped to within a 300-kbp
      region at the chromosome site 11q13. The marker cCLGW567 and the locus
      MAP3K11/D11S546 centromeric and telomeric flanked it, respectively. Northern blot
      analysis, using an ERV9 LTR probe, indicated that most normal tissues examined
      expressed low abundant ERV9 LTR driven mRNAs of various sizes. The most prominent
      expression was found in adrenal glands and testis. However, the level of
      expression varied in the same tissues among different individuals indicating that
      ERV9 mRNA expression probably is inducible in certain tissues or at various cell
      stages.

PMID- 11306805
TI  - Mapping of genes and transcribed sequences in a gene rich 400-kb region on human
      chromosome 11p15.1-->p14.
AB  - We have identified a number of transcribed sequences within a 400-kb interval on
      chromosome 11p15.1--> p14. Six genes and 13 novel transcripts including ESTs,
      cDNAs and exons have been identified and assigned to this region. Comparison of
      mRNA sequence with genomic sequence has enabled us to determine the exon/intron
      structure of four of the genes (NUCB2, PIK3C2A, RPS13 and OR7E14P).

PMID- 11306804
TI  - A high-density transcript map of the human dominant optic atrophy OPA1 gene locus
      and re-evaluation of evidence for a founder haplotype.
AB  - Dominant optic atrophy (DOA, gene OPA1) is the commonest form of inherited optic
      atrophy. Linkage studies have shown that a locus for this disease lies in a 1.4
      cM region at chromosome 3q28-->q29 and have suggested a founder haplotype for as
      many as 95% of the linked families. To aid the identification of candidate genes
      for this disease, we have constructed a Bacterial Artificial Chromosome (BAC)
      contig covering approximately 3.3 Mb and encompassing the OPA1 critical region
      (flanking markers D3S3669 and D3S3562). This physical map corrects errors in the
      marker order reported in the literature, allowing the OPA1 critical region to be
      precisely defined. A reassessment of the founder effect in the light of the
      revised marker order suggests that it may not be as significant as had previously
      been suggested. A high-density transcript map was created by precisely mapping
      genes and expressed sequence tags (ESTs) from GeneMap'99, that have been loosely
      assigned to the region by radiation hybrid mapping. One known gene (KIAA0567
      protein) and 15 ESTs were found to lie within the minimal disease region.
      Analysis of the sequence data already available from within the OPA1 critical
      region allowed the identification and mapping of a further 31 ESTs. The work
      presented in this study provides the basis for the characterisation of candidate
      genes and the ultimate identification of the gene mutated in DOA.

PMID- 11306806
TI  - Identification of the Y chromosome in chinook salmon (Oncorhynchus tshawytscha).
AB  - The Y chromosome in chinook salmon, Oncorhynchus tshawytscha, was identified
      using fluorescence in situ hybridization (FISH) with a probe to a male-specific
      repetitive sequence isolated from this species. The probe highlights the distal
      end of the short arm of an acrocentric chromosome with a DAPI-bright interstitial
      band of variable size. The proximal portion of the short arm of the Y chromosome
      contains 5S rDNA sequences, which are also found on the short arms of six other
      acrocentric chromosomes in this species.

PMID- 11306807
TI  - Cloning of the 18S rDNA gene, an internal transcribed spacer, and the 5' region
      of the 28S rDNA gene of Cope's gray treefrog, Hyla chrysoscelis.
AB  - The location of rDNA genes on the chromosomes of most species is identical within
      that species, usually occurring on the same chromosome or chromosomes. This is
      not the case in Cope's gray treefrog, Hyla chrysoscelis, where the rDNA genes are
      polymorphic for chromosome location. The occasions leading to this polymorphism
      have yet to be determined. The first step in understanding the nature of the
      polymorphism is the characterization of the ribosomal gene array. Here we
      describe the cloning, sequencing, and confirmation, by fluorescence in situ
      hybridization, of the 18S rDNA gene, a region which includes the end of the 18S
      rDNA gene, an internal transcribed spacer, and a portion of the 5' end of the 28S
      rDNA gene in H. chrysoscelis.

PMID- 11306808
TI  - The murine GABA(B) receptor 1: cDNA cloning, tissue distribution, structure of
      the Gabbr1 gene, and mapping to chromosome 17.
AB  - GABA (gamma-aminobutyric acid) is a major inhibitory neurotransmitter in the
      central nervous system (CNS) which activates both ionotropic (GABA(A)/GABA(C))
      and metabotropic (GABA(B)) receptor systems. We identified two alternatively
      spliced cDNA variants of the murine GABA(B) receptor 1 that are predominantly
      expressed in the CNS. Deduced protein structures are highly homologous to the
      previously characterized rat and human receptors. Comparison of the genomic
      structures of mouse and human revealed that alternative splicing occurred at the
      same position, whereas the mouse gene has an additional 5' exon. Radiation hybrid
      mapping, combined with database searches, indicated that the GABA(B) receptor
      gene (Gabbr1) is located on mouse chromosome 17, adjacent to the marker D17Mit24
      in a region homologous to human chromosome 6p21.3.

PMID- 11306809
TI  - Isolation and initial characterization of the mouse Dnmt3l gene.
AB  - We have isolated and sequenced the mouse zinc finger gene, Dnmt3l (DNA cytosine-5
      methyltransferase 3-like), on mouse chromosome 10, showing similarity to members
      of the DNMT3/Dnmt3 family. The Dnmt3l protein contains an ADD zinc finger, which
      Dnmt3l shares with other Dnmt3 family members and Atrx. RT-PCR analysis showed
      Dnmt3l expression in testis, thymus, ovary, and heart, as well as in 7-day, 15
      day, and 17-day mouse embryos.

PMID- 11306810
TI  - Chromosome assignment of four plexin A genes (Plxna1, Plxna2, Plxna3, Plxna4) in
      mouse, rat, Syrian hamster and Chinese hamster.
AB  - We determined chromosome locations of four plexin A subfamily genes, Plxna1,
      Plxna2, Plxna3 and Plxna4, in four rodent species, mouse, rat, Syrian hamster and
      Chinese hamster, by fluorescence in situ hybridization. Plxna1, Plxna2, Plxna3
      and Plxna4 were localized to Chr 6E2, 1H6, XB-C1 and 6B1 in mouse, Chr 4q34.1,
      13q26-->q27, Xq37.1-->q37.2 and 4q21.3-->q22 in rat, Chr 8qb1.1-->qb1.3, 11qb8,
      Xpb8 and 5qb3.3 in Syrian hamster, and Chr 8q1.2, 5q3.7, Xp2.7 and 1q2.2-->q2.3
      in Chinese hamster, respectively. All the mouse and rat plexin A genes were
      localized to chromosome regions where conserved homology has been identified
      among human, mouse and rat.

PMID- 11306811
TI  - Improved radiation hybrid map of rat chromosome 2: colocalization of the genes
      encoding corticotropin-releasing hormone and IL6-receptor with quantitative trait
      loci regulating the inflammatory response.
AB  - We established a radiation hybrid (RH) map of several genes and anonymous markers
      in the lower half of rat chromosome 2, a chromosome region that contains
      quantitative trait loci (QTLs) for blood pressure, diabetes and inflammatory
      response. Two of the newly localized genes (Crh and Il6r) encode proteins
      involved in the regulation of inflammatory and immune events. Our data show that
      they reside within regions that were genetically defined as QTLs controlling the
      inflammatory response. These genes are thus both functional and positional
      candidates.

PMID- 11306812
TI  - Cloning, organisation, chromosomal localization and expression analysis of the
      mouse Prkag1 gene.
AB  - The mammalian 5'-AMP-activated protein kinase (AMPK) is a heterotrimeric protein
      consisting of alpha-, beta- and gamma-subunits. The alpha-subunit is the
      catalytic subunit. The non-catalytic subunits AMPK-beta and AMPK-gamma form,
      together with the catalytic AMPK-alpha, the active kinase complex in mammals and
      its homologue in yeast. The gene for AMPK-gamma-1 has been designated recently as
      PRKAG1. We have isolated mouse Prkag1 cDNA from testis (1623 nt) coding for 330
      aa and we have shown its ubiquitous expression as a 1.8-kb transcript. A
      comparison between mouse, rat and human PRKAG1 cDNA and protein sequences shows
      that the gene is highly conserved among these species with a homology of 96% at
      the protein level. Southern blot analysis indicates that there is more than one
      gene for PRKAG in the mouse genome. Prkag1 contains 12 exons with short introns.
      Analysis of 50 interspecific backcross mice mapped the mouse gene to the distal
      region of chromosome 15.

PMID- 11306813
TI  - Conservation of chromosome 1 in turtles over 66 million years.
AB  - Fluorescence in situ hybridization of a whole chromosome 1-specific probe from
      the yellow-bellied slider turtle (Trachemys scripta) to cells from four other
      species of turtle ranging from a desert tortoise to a loggerhead sea turtle
      resulted in specific and exclusive hybridization to chromosome 1 in all five
      species. Previous observations of conservation in the giemsa banding pattern and
      chromosome morphology and number among turtles are thus extended to the DNA
      sequence level, revealing a cytogenetic stability of chromosome 1 in these
      turtles during the past 66-144 million years. This contrasts with the situation
      for various hominoid species where, in many instances, extensive chromosomal
      rearrangements have been reported in one third of that time period. Our probe,
      which was prepared by microdissecting whole chromosomes from embryonic T. scripta
      fibroblasts and amplifying using DOP-PCR, is the first report of a whole
      chromosome FISH probe for any reptile.

PMID- 11306814
TI  - Isolation, characterization and FISH assignments of horse BAC clones containing
      type I and II markers.
AB  - In order to increase the number of markers on the horse cytogenetic map and
      expand the integration with the linkage map, an equine BAC library was screened
      for genes and for microsatellites. Eighty-nine intra-exon primers were designed
      from consensus gene sequences in documented species. After PCR screening, 38
      clones containing identified genes were isolated and FISH mapped. These data
      allowed us to refine the available Zoo-FISH results, to define ten new conserved
      cytogenetic segments and expand two others, thus leading to the identification of
      a total of 26 conserved segments between horse and human. Interestingly, a new
      homeology segment was detected between ECA6p and HSA2q. Screening BAC clones for
      dinucleotide repeats led to the isolation of 33 microsatellites. Ten of the
      clones each contained at least a polymorphic microsatellite and one specific
      gene. The success of the approach in the production of integrative anchor loci
      and their potential use in localization and analysis of traits of interest by the
      candidate gene and positional cloning approach, are discussed.

PMID- 11306815
TI  - Analysis of DEXI/Dexi refines the organization of the mouse 7C and human 15q11-
      >q13 imprinting clusters.
AB  - Identification of imprinted genes in the Prader-Willi/Angelman syndrome deletion
      region is complicated by the presence of large flanking repeats. While inactive
      copies of DEXI are located within the repeats, we have now localized the active
      DEXI gene to 15q11-->q13 outside the PWS/AS deletion and Dexi to mouse chromosome
      16, suggesting complex evolution of this genomic region in both species.

PMID- 11306816
TI  - Induction and characterization of hypoxanthine-phosphoribosyltransferase (Hprt-)
      deficient cell lines of Akodon cursor (Rodentia, Sigmodontinae).
AB  - Hypoxanthine-phosphoribosyltransferase negative (Hprt-) cell lines derived from
      an Akodon cursor liposarcoma were obtained by induced mutagenesis. All but one
      Hprt- cell line lacked Hprt mRNA transcripts while one (AKO 3) coded for a
      truncated protein. Cell fusion and karyotypic analyses showed that one cell line
      (AKO 1-15) could be successfully used for constructing hybrid panels and allow
      for a clear identification of human chromosomes in hybrid cells.

PMID- 11306817
TI  - Distribution of HOX genes in the chicken genome reveals a new segment of
      conservation between human and chicken.
AB  - Homeobox genes play an important role in the regulation of early embryonic
      development. They represent a family of evolutionarily highly conserved
      transcription factors. In this work, several genes that belong to the four HOX
      gene clusters are assigned by in situ hybridization to four distinct chicken
      chromosomes. The four gene clusters are mapped to 2p2.1 (HOXA), 3q3.1 (HOXB),
      1q3.1 (HOXC) and 7q1.3--> q1.4 (HOXD). We confirm partial homologies already
      detected by genetic mapping between chicken chromosomes 1, 2 and 7 and human
      chromosomes 12, 7 and 2 and we describe a new conserved segment between chicken
      chromosome 3 and human chromosome 17. These results represent the first data that
      confirm the physical linkage between chicken HOX genes and may improve our
      understanding of phylogenetic relationships and genome evolution.

PMID- 11306818
TI  - Assignment of the mouse Extl1 gene to the distal part of chromosome 4 by in situ
      hybridization and radiation hybrid mapping.

PMID- 11306820
TI  - Assignment of p22 dynactin light chain (DCTN3) to human chromosome region 9p13 by
      radiation hybrid mapping.

PMID- 11306819
TI  - Assignment of TACSTD1 (alias TROP1, M4S1) to human chromosome 2p21 and refinement
      of mapping of TACSTD2 (alias TROP2, M1S1) to human chromosome 1p32 by in situ
      hybridization.

PMID- 11306821
TI  - Assignment of SLC17A6 (alias DNPI), the gene encoding brain/pancreatic islet-type
      Na+-dependent inorganic phosphate cotransporter to human chromosome 11p14.3.

PMID- 11306822
TI  - Assignment of sodium-dependent vitamin C transporter (SLC23A1) to bovine
      chromosome band 13q17 by in situ hybridisation.

PMID- 11306823
TI  - Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle
      adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes
      2p13.3 and 14q21, respectively, by physical and radiation hybrid mapping.

PMID- 11306824
TI  - Assignment of TERF1 to chicken chromosome 2q32 and TERF2 to chicken
      microchromosome 11 by fluorescence in situ hybridization.

PMID- 11306825
TI  - The centenary of the Japanese Dermatological Association.

PMID- 11306826
TI  - Facts and myths about electrical measurement of stratum corneum hydration state.
AB  - Some of the views presented in the chapter on 'Examination of stratum corneum
      hydration state by electrical methods' in Skin Bioengineering - Techniques and
      Applications in Dermatology and Cosmetology (Karger, 1998) are in strong
      disagreement with the results from basic research that has been conducted on skin
      impedance measurement over the last decades. This research has e.g. non
      ambiguously shown that the frequency response of the stratum corneum does not
      obey the Cole equation and that measurement depth is strongly dependent on
      measurement frequency. One consequence of these findings is that multifrequency
      electrical measurements on stratum corneum are impossible to achieve in vivo with
      any electrode system known today. Hence, electrical measurements of stratum
      corneum hydration must be conducted at one single, low frequency.

PMID- 11306827
TI  - Bcl-2 expression in skin pathergy reaction of Behcet's disease.
AB  - BACKGROUND: Bcl-2 expression in leukocytes plays an important role in autoimmune
      and inflammatory disease. OBJECTIVE: In the present study, we investigated the
      Bcl-2 expression in the skin pathergy reaction (SPR) of Behcet's disease (BD).
      METHODS: The skin pathergy test (SPT) was performed on 23 patients with BD and 7
      healthy controls. After 48 h, SPT specimens were taken by punch biopsy. Control
      samples were also obtained from the normal skin of 7 patients with BD and 11
      patients with BD-unrelated leukocytoclastic vasculitis. Biopsy specimens were
      evaluated by routine histopathological examination and immunohistochemical Bcl-2
      staining. RESULTS: The SPT was clinically positive in 9 of 23 patients and
      histopathologically positive in 13 but never in the healthy controls. The
      majority of leukocytes in 12 of 13 histopathologically positive specimens were
      stained with Bcl-2. Only 3 BD-unrelated leukocytoclastic vasculitis samples
      showed Bcl-2 positivity. No Bcl-2 staining was found in healthy controls and
      normal skin samples of patients with BD. CONCLUSION: Our data may suggest a role
      of Bcl-2-mediated inflammation in the pathogenesis of the SPR in BD.

PMID- 11306828
TI  - Granzyme-B-containing lymphocyte involvement in epidermal injury in graft-versus
      host disease.
AB  - BACKGROUND: Skin lesions from graft-versus-host disease (GVHD) show histological
      features of epidermal cell death with lymphocyte infiltration. Perforin and
      granzyme B are involved in the process of apoptosis induced by cytotoxic T
      lymphocytes (CTL). OBJECTIVE: To elucidate the role of CTL in the mechanism of
      epidermal injury in GVHD. METHODS: We studied immunohistochemical staining for
      granzyme B and perforin in the skin lesions of 8 patients who developed GVHD
      after bone marrow transplantation. RESULTS: Granzyme-B-positive lymphocytes were
      CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute
      GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it
      was negative. Perforin-positive lymphocytes were observed in the epidermis of the
      specimens from 1 acute and 1 chronic GVHD. CONCLUSIONS: Granzyme B derived from
      CTL may be involved in the mechanisms of epidermal injury in GVHD.

PMID- 11306829
TI  - Clinico-immunological heterogeneity in Comel-Netherton syndrome.
AB  - BACKGROUND: Comel-Netherton syndrome (CN) is characterized by atopic-eczema-like
      skin abnormalities combined with linear ichthyotic lesions, hair shaft
      abnormalities and atopy with high IgE levels. OBJECTIVE: Five children with CN
      are described. In 2 of the 3 CN patients still alive, analysis of cytokines
      regulating IgE synthesis was performed. METHODS: In peripheral blood mononuclear
      cells and cultures of purified T cells, mRNA expression and protein production of
      interleukin 4 (IL-4), IL-13, IL-5 and interferon gamma were analysed. The results
      were compared with the values in age-matched atopic dermatitis patients and
      healthy children. RESULTS: The 5 CN patients showed striking differences in
      disease severity and evolution. Marked differences were found in several
      cytokines in the 2 analysed CN patients. Low percentages of natural killer cells
      were observed in both CN patients. CONCLUSION: The regulation of IgE production
      in patients with CN is varied and complex. The CN patients were heterogeneous in
      terms of Th2 skewing.

PMID- 11306830
TI  - Phototherapy of psoriasis: comparative experience of different phototherapeutic
      approaches.
AB  - BACKGROUND: Broad-band UVB alone or in combination with different topical drugs
      (anthralin, calcipotriol), systemic PUVA and bath-PUVA therapy are very effective
      and well-established treatment modalities for psoriasis. OBJECTIVE: The aim of
      this retrospective study was to assess which of these routinely applied
      phototherapeutic modalities might be most effective and safe for the treatment of
      plaque-type psoriasis. METHODS: Patients (n = 203) with moderate to severe
      (pretreatment Psoriasis Area and Severity Index score between 12 and 35) chronic
      plaque-type psoriasis treated between 1992 and 1998 at our department with either
      UVB (with/without anthralin or calcipotriol; n = 97), systemic PUVA (n = 19) or
      bath-PUVA therapy (n = 87) were evaluated for efficacy, duration of treatment,
      number of treatments necessary for complete remission (CR), cumulative light
      dose, side effects of therapy and duration of remission after therapy. RESULTS:
      No statistically significant difference comparing the efficacy of bath-PUVA (CR
      in 72.4%), PUVA (CR in 89.5%) and UVB phototherapy (CR in 69.1%) was found.
      Although the duration of therapy was significantly longer for bath-PUVA (66 +/-
      42 days) as compared to UVB treatment (50 +/- 27 days), the mean number of
      treatments did not differ significantly between bath-PUVA (28 +/- 12), UVB
      therapy (30 +/- 12) and PUVA (26 +/- 13). Significantly fewer side effects of
      phototherapy were observed with bath-PUVA (14.9%) therapy compared to UVB
      treatment (30.9%). Also, the duration of remission after successful therapy was
      significantly longer for bath-PUVA (8.4 +/- 3.5 months) as compared to UVB
      phototherapy (5.1 +/- 4.2 months). CONCLUSION: Bath-PUVA therapy has some
      advantages over UVB phototherapy in the treatment of psoriasis: fewer UV-related
      acute side effects and a longer period of remission after therapy. However, the
      choice of treatment with either UVB, bath-PUVA or systemic PUVA should also be
      based on a history of previous response to treatment and patient considerations,
      including compliance and responsibility for following the precautions to avoid
      potential side effects.

PMID- 11306831
TI  - Assessment of the clinical effect of topical tacalcitol on ichthyoses with
      retentive hyperkeratosis.
AB  - BACKGROUND: Topical tacalcitol (1alpha,24-dihydroxyvitamin D3) has been
      demonstrated to produce beneficial clinical effects on epidermo
      hyperproliferative disorders such as psoriasis and pityriasis rubra pilaris.
      However, the efficacy of the agent has not been elucidated in retentive
      hyperkeratotic disorders. OBJECTIVE: The object of the study was to assess the
      clinical efficacy of topical tacalcitol against ichthyoses with retentive
      hyperkeratosis; X-linked ichthyosis (XLI), ichthyosis vulgaris (IV), and acquired
      ichthyosis (AI). METHODS: Tacalcitol was topically applied on 9 patients with the
      retention ichthyoses, using a single-blinded, bilaterally paired approach with
      right-left comparison of tacalcitol and the base. RESULTS: Clinical improvement
      obtained by topical tacalcitol exclusively was not superior to that of the
      vehicle alone in any of the ichthyotic patients. CONCLUSION: Topical tacalcitol
      therapy was ineffective against ichthyoses without epidermal hyperproliferation.

PMID- 11306832
TI  - Treatment of classical Kaposi's sarcoma with gemcitabine.
AB  - BACKGROUND: Several drugs are active in aggressive classical Kaposi's sarcoma
      (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and
      able to overcome resistance to previous treatment are advisable when treating
      patients in a second line. Gemcitabine, an analogue of deoxycytidine with
      cytotoxic activity in the treatment of solid tumours, has been found to have no
      serious side-effects. OBJECTIVE: To evaluate the usefulness of treating patients
      affected by aggressive CKS with gemcytabine. METHODS: Twelve patients with a
      recurrent aggressive form of CKS previously treated with chemotherapy were
      treated with gemcitabine. The drug was administered intravenously at the dose of
      1.2 g/week for 2 weeks, followed by a 1-week interval, until maximal response was
      reached. Objective responses and toxicity were evaluated according to WHO
      criteria. RESULTS: Eleven evaluable patients achieved an objective response: CR
      in 1/11 and PR in 10/11. Toxicity was limited. CONCLUSION: This study shows the
      usefulness of treating patients affected with aggressive CKS with gemcitabine, in
      order to obtain control of the disease and to reduce the related symptoms as well
      as to overcome a possible resistance to previous treatments.

PMID- 11306833
TI  - Cutaneous leukocytoclastic vasculitis in dermatomyositis suggests malignancy.
AB  - BACKGROUND: Dermatomyositis (DM) is a rare connective tissue disease which has
      been shown to be associated with an underlying malignancy. OBJECTIVE: Evaluation
      of the prevalence of malignancy in DM at our clinic and search for
      characteristics of the paraneoplastic form of disease. METHODS: Retrospective
      review of patient files and histology reports over the period from 1991 to 1998.
      RESULTS: 23 patients (14 women and 9 men) with DM could be identified in this
      time period with a median age at diagnosis of 48 years. Malignancies were found
      in 5 (22%) cases. The skin biopsies of all patients showed features of DM; in 7
      cases, a leukocytoclastic vasculitis was detected. Four of the 5 cases with an
      associated malignancy demonstrated histologically a vasculitis in lesional skin,
      compared to only 3 out of 18 cases without malignancy (p < 0.05, Fisher's exact
      test). CONCLUSION: Our data suggest that vasculitis in lesional skin biopsies has
      a predictive value for the presence of underlying malignancy.

PMID- 11306834
TI  - Widespread cutaneous carcinomas associated with human papillomaviruses 5, 14 and
      20 after introduction of methotrexate in two long-term PUVA-treated patients.
AB  - BACKGROUND: PUVA treatment for patients with severe psoriasis has been
      demonstrated to be highly effective. However, an increased risk of nonmelanoma
      and melanoma skin cancers has been reported. It is generally accepted that the
      risk of squamous-cell carcinoma (SCC) is significantly increased in patients with
      long-term PUVA therapy. The role of methotrexate (MTX) and infection with
      oncogenic human papillomaviruses which may act as cocarcinogens is poorly
      documented. CASE REPORTS: Two cases of multiple SCCs associated with numerous
      PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent
      treatment with MTX are presented. In 1 case, the tumor progressed to metastatic
      SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the
      presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV
      5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification.
      CONCLUSION: These observations support the concept that long-term PUVA treatment
      is carcinogenic and rise questions concerning an additional influence of MTX in
      the development and progression of skin cancer. The risk of metastatic SCC seems
      to be underestimated in high-dose PUVA-treated patients due to longer latency for
      developing metastases and the small number of studies with long-term follow-up.
      Treatment with MTX should be considered cautiously in patients previously exposed
      to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic
      skin lesions detected only with the highly sensitive nested PCR method is not
      necessarily a proof of their implication in skin carcinogenesis.

PMID- 11306835
TI  - Cutaneous nocardiosis of the chest wall and pleura--10-year consequences of a
      hand actinomycetoma.
AB  - We report an unusual case of primary cutaneous nocardiosis due to Nocardia
      otitidiscaviarum presenting first as a mycetoma of the right hand and wrist. The
      patient refused treatment and was lost to follow-up until he showed up 10 years
      later with numerous discharging large sinuses and abscesses on the upper right
      quadrant of the chest wall and in the right armpit. Roentgenograms revealed
      pleural masses. Histology was in keeping with the diagnosis of mycetoma.
      Treatment with amikacin, rifampicin and co-trimaxole proved to be successful.

PMID- 11306836
TI  - Pigmented Paget's disease of the male breast: report of a case.
AB  - An 83-year-old man with pigmented Paget's disease of the breast is reported. He
      had a blackish swollen right nipple with bloody discharge that lasted for 8
      months. Histopathology of the lesion disclosed intraepidermal and dermal atypical
      cells forming small clusters and underlying intraductal carcinoma. Melanocytes
      were dispersed in the epidermis. Dermal melanophages were also detected. The
      atypical cells were positive for carcinoembryonic antigen, human-milk fat globule
      protein and a recently described new antigen, RCAS-1, but negative for S-100 or
      HMB-45. We diagnosed this case as Paget's disease of the male breast. Paget's
      disease of the breast is usually nonpigmented and occurs almost exclusively in
      women. Pigmented Paget's disease of the male breast is extremely rare, and only a
      few cases have been reported. Albeit rare, pigmented Paget's disease has to be
      included in the differential diagnosis of pigmented lesions of the nipple.

PMID- 11306837
TI  - Drug-induced linear IgA bullous dermatosis mimicking toxic epidermal necrolysis.

PMID- 11306838
TI  - Cellular blue nevus in association with phototherapy.

PMID- 11306839
TI  - Acute generalized exanthematous pustulosis due to teicoplanin.

PMID- 11306840
TI  - Aspergillus versicolor infection of the external auditory canal successfully
      treated with terbinafine.

PMID- 11306841
TI  - Localized morphea after silicone-gel-filled breast implant.

PMID- 11306842
TI  - Paraneoplastic pemphigus with constrictive bronchiolitis obliterans.

PMID- 11306844
TI  - Bilateral corneal melting in a patient with paraneoplastic pemphigus.
AB  - An 80-year-old man, with a solid abdominal tumor and multiple skin lesions, was
      admitted to the hospital because of a perforated right cornea and an impending
      perforation of the left. The clinical, histological, immunohistological and
      immunoprecipitation findings of the skin lesions were consistent with Anhalt's
      criteria for paraneoplastic pemphigus (PNP). The underlying malignancy proved to
      be an incurable peripheral neuronal shaft tumor. Both conjunctivae appeared
      normal. The right eye revealed a flat anterior chamber, due to a spontaneous,
      central corneal perforation. The central part of the left cornea had severely
      thinned, resulting in a descemetocele, which eventually perforated. Multiple
      surgical interventions were needed to restore the anterior chamber in both eyes.
      Although a causative association between PNP and corneal perforation could not be
      demonstrated, we think that corneal melting should be added to the list of ocular
      complications in patients with PNP.

PMID- 11306845
TI  - Paraneoplastic pemphigus in a patient with a thymoma.
AB  - A 76-year-old woman, with a history of thymoma, presented with a painful
      extensive stomatitis, painful paronychia, lichenoid papules on the hands and
      superficial erosions on the neck and the trunk. Histological examination showed
      lichenoid changes, acantholytic blister formation and apoptotic keratinocytes.
      Direct immunofluorescence was positive for IgG both in the epidermal
      intercellular spaces and along the basement membrane zone. Indirect
      immunofluorescence was similarly positive in a pemphigus vulgaris pattern. There
      was only a partial response to intravenous corticoids. These findings allowed the
      diagnosis of paraneoplastic pemphigus. The diagnostic characteristics,
      histopathology and the differential diagnosis of this disease are discussed.

PMID- 11306846
TI  - Superficial granulomatous pyoderma gangrenosum of the face, successfully treated
      by ciclosporine: a long-term follow-up.
AB  - We report a case of the superficial granulomatous (vegetating) form of pyoderma
      gangrenosum, involving the forehead and the left temporal area in a 44-year-old
      woman. No association with other pathologies could be found. Lesions responded
      dramatically to systemic ciclosporine (5 mg/kg/day), and complete healing was
      reached after 6 months. Doses were tapered progressively. Treatment was
      discontinued after 4.5 years. Discontinuation was not followed by recurrence of
      the disease. Healing is maintained after another 4.5 years of follow-up.

PMID- 11306847
TI  - Autologous cellular suspensions and sheets in the treatment of achromic
      disorders: the need for future controlled studies.
AB  - Transplantation techniques using cultured and noncultured keratinocyte and/or
      melanocyte suspensions or sheets have been reported as successful in inducing
      repigmentation in achromic epidermal diseases such as vitiligo and piebaldism.
      However, the role of a lot of variable factors in the transplantation procedure
      remains unclear. Occasionally control sites are included in the reported patient
      series. We point out the need for future controlled studies when performing
      transplantations of cellular suspensions and sheets. This approach will help to
      understand how these techniques induce repigmentation and may eventually indicate
      the essential requirements for successful results.

PMID- 11306848
TI  - Surgical techniques for vitiligo: a review.
AB  - Although the treatment of vitiligo has improved during the last decade, therapy
      is still not satisfying for many patients. This is probably due to the fact that
      the aetiopathogenesis is unknown. Several treatment modalities, such as PUVA, UVB
      and local corticosteroids are currently used in the treatment of active vitiligo.
      However, these treatments usually induce incomplete repigmentation. Surgical
      methods intended to repigment leucoderma are an interesting therapeutic option if
      patients have stable disease. Two types of surgical techniques are available:
      tissue grafts and cellular grafts, with in between autologous cultured epithelial
      grafts. Tissue grafts are full-thickness punch grafts, split-thickness grafts and
      suction blister grafts. With tissue grafts, only a limited surface area can be
      treated but with good results in the majority of cases. Cellular grafts include
      non-cultured keratinocytes/melanocytes and cultured melanocytes. The exact
      success rate of repigmentation with cellular grafts is still unknown, since only
      a small number of studies have been published. Starting from autologous cellular
      suspensions, epithelial grafts of various compositions can be cultured in vitro.
      They can be used for larger areas. The purpose of this review is to describe the
      applications of different surgical techniques used to treat recalcitrant
      vitiligo.

PMID- 11306849
TI  - Beneficial effects of softened fabrics on atopic skin.
AB  - There is general concern about the possible cutaneous adverse effects of wearing
      garments treated with household laundry products, particularly on atopic skin.
      Our objective was to compare softened and non- softened fabrics in a forearm wet
      and dry test, under conditions simulating real-life conditions. Twenty atopic
      volunteers entered a single-blind 12-day (3 sessions per day) forearm wetting and
      drying test. Cotton fabrics were machine washed and liquid fabric conditioner was
      added or not to the final rinse. To simulate conditions of skin damage, a dilute
      solution of sodium lauryl sulphate was applied under occlusion to the forearm of
      each volunteer before the start of the study. Skin effects were evaluated by
      visual grading (redness, dryness and smoothness), squamometry and in vivo
      instrumental measurements (capacitance, transepidermal water loss and
      colorimetry). Rubbing of atopic skin with fabrics generally resulted in discrete
      to moderate alterations of the structure of the stratum corneum. Both for control
      and pre-irritated skin, all measured parameters indicated that softened fabric
      was less aggressive to the skin than unsoftened fabric. In the case of pre
      irritated skin, the recovery of the skin was significantly faster when rubbed
      with softened than with unsoftened fabrics. In conclusion, softened fabrics help
      mitigate the skin condition in atopic patients.

PMID- 11306850
TI  - Effect of ketoconazole 1% and 2% shampoos on severe dandruff and seborrhoeic
      dermatitis: clinical, squamometric and mycological assessments.
AB  - Ketoconazole (KET) is active to control dandruff and seborrhoeic dermatitis.
      Objective assessments comparing the 1% and 2% shampoo formulations are scant.
      This open, randomized parallel-group trial was carried out to differentiate the
      effectiveness of KET 1% and 2% in severe dandruff and seborrhoeic dermatitis. A
      total of 66 patients with severe dandruff or seborrhoeic dermatitis were
      randomized to each of the two groups. A 2-week run-in phase was followed by a 4
      week treatment phase, in turn followed by a 4-week follow-up. The efficacy of
      treatments was evaluated by combining squamometry X, Malassezia spp. counts and
      clinical assessments. After 2 and 4 weeks of treatment, KET 2% was significantly
      superior over KET 1% (p < 0.001) for decreasing both in flakiness and Malassezia
      density from baseline. The same trend was observed in the mean change from
      baseline in the overall dandruff severity score. Only 6 mild adverse events were
      reported. During follow-up KET 2% showed a trend to fewer relapses than KET 1%.
      KET 2% had superior efficacy compared to KET 1% in the treatment of severe
      dandruff and scalp seborrhoeic dermatitis. Biometrological evaluations were
      correlated with the clinical improvements and therefore useful to incorporate in
      future dandruff studies.

PMID- 11306851
TI  - Influence of body posture and gravitational forces on shear wave propagation in
      the skin.
AB  - The body posture and gravitational forces govern in part the intrinsic skin
      tensile strength because they influence the orientation of the dermal fibre
      networks. Our objective was to assess changes in shear wave propagation in the
      skin according to the body posture and orientation of the gravitational forces.
      The study was performed in 30 middle-aged women with a normal body mass index.
      The Reviscometer was used to assess the mechanical wave propagation on the volar
      forearm in extension or flexion. Similar measurements were made on the supra
      areolar region of the breast when the trunk was in the horizontal or vertical
      position. Four measurements were made in each of 4 directions at given angles
      with regard to the body axis. The device gave reproducible data. Shear wave
      propagation was influenced by the body posture. The intra-individual variability
      in shear wave velocity according to the directions of measurements increased when
      the tissues were in a relaxed position. Skin tensile anisotropy increased in a
      relaxed body posture. Shear wave propagation may be a convenient non-invasive
      tool to better identify the natural skin tension lines in the skin, thus refining
      the orientation of incision during cutaneous surgery.

PMID- 11306852
TI  - Dual presentation of extranodal marginal B-cell lymphoma involving the skin,
      viscera and bones.
AB  - A 65-year-old man presented with an erythematous indurated plaque on the scalp
      and forehead. A low-grade marginal-zone B-cell lymphoma with small cells and
      kappa-chain monoclonality was diagnosed. Radiotherapy was initiated. He soon
      developed abdominal pain and hematemesis. A high-grade marginal-zone B-cell
      lymphoma with large cells and lambda-chain predominance was disclosed
      infiltrating the stomach and lungs. Bone localizations were also found. There was
      no evidence for lymph node and bone marrow involvement. The distinct cytological
      and immunophenotypic presentations in the skin and viscera are a puzzling
      finding.

PMID- 11306853
TI  - Scytalidium dimidiatum melanonychia and scaly plantar skin in four patients from
      the Maghreb: imported disease or outbreak in a Belgian mosque?
AB  - Scytalidium dimidiatum is a geophilic dematiaceous, non-dermatophyte mould that
      can become a pathogen for plants and humans particularly in tropical and
      subtropical regions. We report 4 cases of S. dimidiatum onychomycosis presenting
      clinically as thickened and dark toenails. The skin of the soles was scaly. The
      time and location of the contaminations were uncertain. Indeed, the patients were
      ancient immigrants from the Maghreb to Belgium. They were also regularly
      travelling to their countries of origin. They were also often barefoot in the
      same Belgian mosque. The disease was unresponsive to current oral antifungal
      treatments.

PMID- 11306854
TI  - Minimizing the risks of missing a contact allergy.
AB  - The diagnosis of a contact allergy can be missed in the various stages of the
      allergological investigation: the clinical examination of the patients, the
      anamnesis, the skin testing as well as the determination of the relevance of a
      positive test. This is illustrated by means of examples from the literature.

PMID- 11306855
TI  - Diagnostic and classification criteria for the Guillain-Barre syndrome.
AB  - BACKGROUND: Diagnostic criteria for the Guillain-Barre syndrome (GBS) have been
      available since 1978. Since then, several variants have been described. More
      recently, a distinction has been made between pure motor forms, severe sensory
      forms, primary axonal and primary demyelinating varieties. Associations of
      clinical characteristics, and specific infections and the presence of
      antiganglioside antibodies have been found. For further studies on GBS, it is
      therefore necessary to reconsider the available diagnostic criteria and add
      additional criteria for subclassification. METHODS: A panel of (20) experts was
      formed. The literature representing the recent developments in GBS
      subclassification was reviewed. Following a consensus protocol, diagnostic and
      classification criteria were formulated. RESULTS: The diagnosis of GBS can
      usually be made on clinical characteristics. A schedule for subclassification has
      been made to cover also the clinical variants in a systematic manner.

PMID- 11306856
TI  - A new visual rating scale for white matter low attenuation on CT.
AB  - The pathological substrate and clinical significance of white matter low density
      change on computed tomography (CT) remains incompletely understood, hampered by
      suboptimal rating scales. We developed a new scale and applied it to 647 CTs in
      382 patients. White matter change was categorised by region (anterior and
      posterior frontal, parietal, occipital), severity (mild, moderate, severe) and
      extent (periventricular, extending to deep white, full thickness). Multiplying
      extent by severity gave regional scores, which were summated to give an overall
      score. CTs were read separately by 2 radiologists. Intraobserver reliabilities
      were 0.69 and 0.55, interobserver 0.70 (kappa values). Each assessment required
      only 1 min.

PMID- 11306857
TI  - Atherosclerotic aortic arch plaques in cryptogenic stroke: a microembolic signal
      monitoring study.
AB  - BACKGROUND AND PURPOSE: To find out the prevalence of relevant atherosclerotic
      plaques in the aortic arch and their potential role as a source of embolism in
      cryptogenic stroke. METHODS: We performed a transoesophageal echocardiography
      (TEE) on 49 patients with cryptogenic stroke from a total series of 212 non
      selected patients with acute ischaemic stroke studied prospectively by cranial
      computed tomography (CT), colour-duplex and transcranial Doppler (TCD) sonography
      with micro-embolic signal (MES) monitoring. Cryptogenic stroke was diagnosed in
      those patients without carotid or intracranial stenosis > 50%, nor lacunar or
      cardio-embolic strokes. We defined relevant plaques as those > or = 4 mm thick
      located in the ascending aorta or proximal arch. RESULTS: Twenty-three patients
      (46.9%) had atherosclerotic aortic plaques (AAP): 3 in the ascending aorta (in 1
      > or = 4 mm), 11 in the proximal aortic arch (in 4 > or = 4 mm) and 9 in the
      descending aorta (in 5 > or = 4 mm). Hence, 5 patients (10.2%) had relevant
      plaques. Aortic plaques were significantly related to older age (p < 0.001) and
      male gender (p = 0.042). A carotid artery stenosis < 50% was found in 39% of
      patients with AAP and in 8% of those without AAP (p = 0.009). MES were detected
      in 3 patients with plaques > or = 4 mm thick, but not in those without AAP or
      with AAP < 4 mm thick (p = 0.006). CONCLUSION: Although few patients with
      cryptogenic stroke had relevant plaques in our non-selected population, our
      results support the hypothesis that relevant aortic plaques have embolic
      potential.

PMID- 11306859
TI  - Double dissociations between neglect tests: possible relation to lesion site.
AB  - In 20 patients who had suffered a first right hemisphere stroke, we examined the
      prevalence of double dissociations between the results of a star cancellation and
      a line bisection test. Both are common methods to assess spatial hemineglect.
      Within the group of neglect patients, we found no significant correlation between
      the two tasks. Furthermore, 5 patients with impaired performance on one of the
      tests were within the normal range on the other one. In agreement with
      experimental studies, we argue that spatial hemineglect is not a unitary
      syndrome. Furthermore, the findings in one of our patients are compatible with
      the view that an isolated deficit on cancellation tasks might follow from a
      lesion in the right anterior cingulate gyrus.

PMID- 11306858
TI  - S-100 protein and neuron-specific enolase as markers of subclinical cerebral
      damage after cardiac surgery: preliminary observation of a 6-month follow-up
      study.
AB  - Cerebral damage remains one of the hazards related to cardiac surgery with
      cardiopulmonary bypass. The use of biochemical markers of cerebral injury may be
      of practical value. We investigated the plasma release patterns of S-100 protein
      and neuron-specific enolase (NSE) during the intervention and their relationship
      with the development of neuropsychological deficits assessed 6 months after the
      intervention in 16 patients undergoing elective cardiac surgery with
      cardiopulmonary bypass. Both S-100 and NSE significantly increased peri- and
      postoperatively. Significant correlations were found between values measured at
      several time points and impaired performance in a few tests at the 6-month follow
      up. A stratification into two age subgroups led to the hypothesis that age might
      have a confounding or a modifying effect on the association between S-100 and NSE
      levels, and cognitive impairment.

PMID- 11306860
TI  - Transient ischaemic attack: a common initial manifestation of cardiac myxomas.
AB  - BACKGROUND AND AIMS: Cardiac myxomas may present clinically with many different
      features. Since highly effective treatments exist, it is important that they are
      diagnosed quickly in order to avoid further complications. Our aim was to
      determine the influence of neurological presentation in diagnosis and prognosis
      of cardiac myxomas. METHODS: We have reviewed the clinical charts of 28 patients
      diagnosed with cardiac myxomas seen at our centre in the last 20 years. RESULTS:
      Mean age at diagnosis in patients with neurological events was 49.22 years and
      60.84 years in those without neurological manifestations (p = 0.0325). Most
      frequent presentations were: cardiac manifestations (92.8%), general
      manifestations (71.4%) and embolic events (39.3%). Nine patients (32.1%)
      presented with cerebral embolism; 7 of whom presented with transient ischaemic
      attacks (TIA), which was the first manifestation in 6 of them; 3 of them later
      suffered complete cerebral infarction with sequelae. Echocardiography confirmed
      diagnosis in 26 out of 27 patients in which it was performed. None of the
      patients presented neurological symptoms after surgery. CONCLUSION: The most
      frequent initial neurological manifestation in our series was TIA. Nevertheless,
      none of the patients were diagnosed after the first neurological symptom.
      Although the contribution of cardiac myxomas to the total amount of TIA is low,
      since surgery is highly effective and of low risk, and patients with neurological
      manifestations are younger, it is vital to consider the possibility of cardiac
      myxoma after a TIA of unknown origin.

PMID- 11306861
TI  - Mutation in the methylenetetrahydrofolate reductase gene might be a risk factor
      for cerebrovascular disease in peripartum and under oral contraceptive use.
AB  - Nine women (age 22-43 years) with cerebrovascular diseases (CVD) related to
      pregnancy, puerperium or contraceptive use were studied. Five were pregnant, 2
      were post partum and 2 were taking oral contraceptives. All under- went a
      complete etiological examination including assessment for the thermolabile C677T
      mutation in the methylenetetrahydrofolate reductase (MTHFR) gene mutation. Three
      of the 9 patients were homozygotic for the C677T MTHFR mutation, and 3 were
      heterozygotic. In these 6 patients, no other etiology could be found. Mutation in
      the thermolabile MTHFR gene might be an important cause for CVD related to
      peripartum or contraceptive use.

PMID- 11306862
TI  - The predictive value of achieved motor milestones assessed in 441 patients with
      infantile spinal muscular atrophy types II and III.
AB  - Proximal spinal muscular atrophy (SMA) is classified into three main subtypes (I
      III), defined by age at onset and achieved motor milestones. As age at onset can
      be very early in SMA II and III (IIIa, onset < 3 years) and does not necessarily
      correlate with prognosis, the question arises whether the child can be correctly
      assigned to a specific SMA type at the time of presentation based on the
      assessment of motor function. Therefore we studied the motor milestones in 175
      SMA type II and 266 SMA type III patients. In SMA II, 73% of the patients sat
      within the normal age range (up to 9 months), the remainder learned to do so at
      ages between 10 and 30 months. In SMA III, the walking milestone was passed with
      delay (given an upper normal limit of 18 months) in 10% of all and 16% of SMA
      IIIa patients (median age 13 months, range 9-53 months). There was a correlation
      between late sitting and walking in SMA III, since those who sat after 9 months
      were responsible for the majority of delayed walkers. The median age when
      becoming chairbound did not differ between early-onset SMA III patients who
      walked with delay and those who walked within the normal age range (10.2 versus
      10.5 years). In conclusion, a significant proportion of patients with early-onset
      SMA classified as SMA II on the basis of achieved motor function turned out to be
      SMA III at later follow-up. It is important to reassess a child in the first 2-4
      years, to determine whether walking can be achieved with or without aids, as
      children who start to walk late have a similar favourable outcome for ambulation
      compared to earlier walkers.

PMID- 11306863
TI  - Hemiballism-hemichorea and posterior communicating artery stenosis.

PMID- 11306864
TI  - Involvement of CD45RO+ T lymphocyte infiltration in a patient with primary
      angiitis of the central nervous system restricted to small vessels.

PMID- 11306865
TI  - Spinal and bulbar muscular atrophy without tongue atrophy.

PMID- 11306866
TI  - Guillain-Barre syndrome and allopurinol-induced hypersensitivity.

PMID- 11306867
TI  - Hypermetabolism of the medial temporal lobe in limbic encephalitis on (18)FDG-PET
      scan: a case report.

PMID- 11306868
TI  - Internal ophthalmoplegia as a presenting sign of herpes zoster ophthalmicus.

PMID- 11306869
TI  - Reversible leukoencephalopathy associated with thrombotic thrombocytopenic
      purpura.

PMID- 11306870
TI  - Cytokine production from peripheral mononuclear cells in 2 patients affected by
      adrenomyeloneuropathy.

PMID- 11306871
TI  - Cortical reflex action myoclonus in neurosyphilis.

PMID- 11306872
TI  - The future of urology in Europe: an overview from the European association of
      urology.
AB  - INTRODUCTION: In order to be able to influence and monitor future developments
      for urologists, strategies should be promoted in advance to guarantee the future
      of the speciality and to accommodate the inevitable changes. Faced with this
      challenge, the EAU, through its Strategy Planning Office (SPO), has prepared a
      document which is offered, here, in abbreviated form, to the European and
      international urological communities for general consideration. MATERIAL AND
      METHODS: A group of subjects, related to the domains and internal consistency of
      urology as a speciality, were selected and discussed among the members of the SPO
      and later submitted to open consultation among distinguished members of the
      urological community. The topics selected for discussion included: what is
      urology; urology in the university; sub-specialization in urology; training in
      urology; does kidney transplantation belong to urology, and others. RESULTS: It
      is shown that urology is going through an exciting and hazardous transition
      period. Urology has conflicting problems in its traditional domains due to
      changes in health care policy, and internal identification problems due to its
      permanent expansion and sub-specialization options. Weaker points are its
      relation with primary care medicine (shared care options), the presence and role
      of urology in institutions such as the university, department of surgery,
      children's hospitals, administration, etc.; the desegregating effect of the sub
      specialities; the increasing encroachment of other specialities, and the
      increasing outpatient effect of technological progress. CONCLUSION: An action
      plan is proposed to confront these changes without loosing manpower, internal
      consistency or social image and improving patient care quality, excellence of
      training and scientific progress.

PMID- 11306873
TI  - Comparison of individual urologists' performance.
AB  - OBJECTIVE: In the last few years, comparative outcome quality statistics have
      been one of the key topics for discussion in health care. Comparative audits
      using overall mortality and morbidity figures can be misleading as they do not
      take into account variations in urological procedure and patient fitness. The
      purpose of our study was to compare the crude operative morbidity and mortality
      rates with the predicted rates using an established scoring system (POSSUM).
      MATERIALS AND METHODS: To examine these effects, we compared 5 urological
      operations (transurethral resection of the prostate, transurethral resection of
      the bladder, radical nephrectomy, suprapubic enucleation of the prostate and
      radical prostatovesiculectomy) performed by 2 urologists in a prospective study
      during a 12-month period. POSSUM consists of a simple preoperative physiological
      score, a postoperative score and defined kinds of complications. RESULTS: One
      urologist operated on 160 patients, with an operative mortality of 2.5% and
      morbidity of 31.3%. The other urologist operated on 144 patients, with an
      operative mortality of 0.7% and morbidity of 9%. At first sight, there appear to
      be significant differences in operative outcome between the 2 urologists.
      However, analysis using the POSSUM system predicts a mortality rate of 3.1% for
      the first urologist and 0.7% for the second urologist (morbidity rates of 35% for
      the first urologist and 10.4% for the second urologist). Receiver operating curve
      analysis demonstrated no significant difference between the 2 urologists.
      CONCLUSION: The present study demonstrates how misleading crude mortality and
      morbidity figures can be when comparing different urologists. By producing a
      single assessment of physiological status at the time of operation and of
      operative severity, POSSUM analysis allows a more realistic comparison between
      different urologists.

PMID- 11306874
TI  - Surgery for stress incontinence: a non-randomised trial of colposuspension,
      needle suspension and anterior colporrhaphy.
AB  - OBJECTIVE: To compare the outcome, 12 months after surgery, of three principal
      categories of procedure (colposuspension, needle suspension and anterior
      colporrhaphy) used for treating stress incontinence. METHODS: A non-randomised
      trial design comparing 221 colposuspensions, 54 needle suspensions and 130
      anterior colporrhaphies performed by 49 surgeons in 18 hospitals in the North
      Thames health region in 1993-1994. Four outcomes were considered: complications,
      severity of stress incontinence, social impact of incontinence, and activities of
      daily living score. Results were adjusted, using logistic regression, for 13 case
      mix variables. RESULTS: Significant differences existed between the three
      procedures in the characteristics of the patients. The cure rate varied by
      procedure (colposuspension 34% dry; needle suspensions 13%; anterior colporrhaphy
      19%). Two thirds of women, however, reported an improvement (colposuspension 75%;
      needle suspension 68%; anterior colporrhaphy 55%). After adjusting for
      confounders, colposuspension was significantly more likely to result in an
      improvement than anterior colporrhaphy (odds ratio 2.2). While this was reflected
      in improvements in the social life of the women, the difference between
      procedures did not reach statistical significance (p = 0.05). CONCLUSION: These
      results suggest surgery for stress incontinence in typical settings is not as
      good as reported in textbooks. This is mostly because this study was based on
      women's own reports (and not surgeons' reports) and partly because of the
      unselected nature of the patients. The information on outcomes given to patients
      should be reviewed and a large, pragmatic randomised trial including patient
      assessed outcomes is needed.

PMID- 11306875
TI  - Transurethral implantation of macroplastique for the treatment of female stress
      urinary incontinence secondary to urethral sphincter deficiency.
AB  - OBJECTIVE: To assess the results of transurethral implantation of Macroplastique
      in women with stress incontinence secondary to urethral sphincter deficiency
      using subjective and objective outcome measures. METHODS: A total of 60 women
      with genuine stress incontinence secondary to intrinsic urethral sphincter
      deficiency were treated with transurethral implantation of Macroplastique. The
      patients had undergone a mean of 1.9 (range 0-7) previous episodes of continence
      surgery. Up to three treatment episodes were used, if necessary. The outcome was
      assessed by telephone interview (56 patients, mean follow-up period 19 months)
      and videocystometry (41 patients, mean follow-up period 16 months). Transurethral
      ultrasound scanning was performed in a further 9 patients. RESULTS:
      Symptomatically, 19.6% of the women interviewed by telephone considered
      themselves cured of their incontinence or were no longer using pads. A further
      41.1% said their symptoms had significantly improved. Pad usage was reduced from
      a median of five to three pads per day (p < 0.001). Videocystometry in 41 women
      (mean follow-up period 16 months) was normal in 16 patients (39%) and showed
      genuine stress incontinence in 18 (43.9%) and detrusor instability in 12 patients
      (29.3%). Overall, 71.4% stated that they would undergo the procedure again under
      the same circumstances, and 80.4% would recommend this form of treatment to a
      friend with the same condition. Transurethral ultrasound scanning was performed
      in 9 patients (5 subjectively improved or cured, 1 patient with persistent
      symptoms but normal cystometry, and 3 patients with persistent genuine stress
      incontinence). Hyperechoic foci were seen surrounding the proximal urethra,
      consistent with implanted Macroplastique boluses. When completely encircling the
      urethra, the outcome was generally good. A total of 10 patients have undergone or
      are awaiting open surgery, and 3 are awaiting repeat implantation. CONCLUSION:
      Sustained improvement or cure of genuine stress incontinence has been achieved
      using Macroplastique in a large proportion of women with intrinsic sphincter
      deficiency, often following previous unsuccessful continence surgery.
      Transurethral ultrasound may prove to be a clinically useful imaging technique
      for the assessment and subsequent management of treatment failure following
      Macroplastique implantation.

PMID- 11306876
TI  - The progression of benign prostatic hyperplasia: examining the evidence and
      determining the risk.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is often associated with
      enlargement of the prostate gland, lower urinary tract symptoms, decreased
      urinary flow and a reduced quality of life. Furthermore, if the symptoms
      associated with BPH are left untreated, serious complications, such as acute
      urinary retention, may ensue. Evidence is emerging from long-term clinical
      studies to suggest that BPH is a progressive disease, with some patients
      progressing much more rapidly than others. OBJECTIVE: This article aims to
      explore the natural history of BPH progression from a molecular, pathological and
      clinical perspective, with emphasis on the key clinical evidence to support the
      progressive nature of this disease. How our increased understanding of the
      disease and of the risk factors for BPH progression might be applied to improve
      current management practices are also discussed. CONCLUSION: Strategies to
      identify patients most at risk and guidelines directed towards long-term
      management, in addition to short-term treatment, may be useful in helping to
      prevent BPH progression.

PMID- 11306877
TI  - Microwave thermotherapy in patients with benign prostatic hyperplasia and chronic
      urinary retention.
AB  - OBJECTIVE: To evaluate microwave thermotherapy as a treatment option for benign
      prostate hyperplasia (BPH) in patients with chronic retention and an indwelling
      catheter. PATIENTS AND METHODS: 24 unselected patients, 53-91 years old (mean age
      73 years) with chronic urinary retention and an indwelling catheter were treated
      with ProstaLund Feedback TreatmentR. Patients had had an indwelling catheter for
      1-12 months prior to treatment. ProstaLund Feedback Treatment is an enhanced
      microwave treatment where the actual intraprostatic temperature is monitored and
      used to control the microwave power. RESULTS: 19 (80%) of the 24 patients were
      successfully relieved of their indwelling catheter with satisfactory peak flow,
      residual urine and symptom score. Treatment failed in 5 (20%) out of the 24
      cases. The reasons of failure were identified in all 5 cases and indicate that
      the method may be less suitable in case of a median lobe or large protruding
      lobes into the bladder. There were no serious complications such as bleeding
      requiring hospital intervention, sepsis or urine incontinence. Isolated cases of
      urinary infection occurred. CONCLUSION: The satisfying outcome of a 1-hour-long
      out-patient procedure for this patient category suggests that ProstaLund Feedback
      Treatment may be a good alternative to surgery for BPH patients with chronic
      retention and an indwelling catheter.

PMID- 11306878
TI  - Initial experience with a new transurethral microwave thermotherapy treatment
      protocol '30-minute TUMT'.
AB  - OBJECTIVE: We report on our experience with a less invasive treatment for benign
      prostatic hyperplasia (BPH), a high-energy '30-minute' treatment algorithm of
      transurethral microwave thermotherapy (TUMT). As initial investigators of this
      new device, we have tested its safety, tolerance and efficacy. METHODS: From
      April 1998 to May 1999, all males attending our Outpatient Clinic for symptomatic
      BPH were evaluated with physical examination, symptoms questionnaire, bladder and
      prostate ultrasound scan, cystomanometry and pressure-flow study. Sixty-one males
      with: prostate volume > 30 cm3, prostate length > 25 mm, Qmax < 15 ml/s, IPSS >
      or =13, MSS > or = 8, and without excessive middle lobe, underwent one session of
      30-min TUMT treatment after informed consent was obtained. Treatments were
      performed on an outpatient basis and with oral sedation and local analgesia.
      Follow-up visits were scheduled for 2 weeks, 1, 3, 6 and 12 months post
      treatment. RESULTS: Fifty-six out of 61 patients (92%) completed the 6-month
      follow-up visit: mean MSS improved from 12.0 to 4.3; IPSS changed from 18.1 to
      5.2. The mean maximum flow rate improved from 9.1 to 17.8 ml/s and the mean post
      void residual decreased from 92 to 18 ml. Cavities within prostatic tissue were
      observed in 54 out of 56 patients (95%). The most frequent adverse event was UTI
      (21.3%); no major complications were observed. CONCLUSION: Our experience
      demonstrated that 30-min TUMT is a safe, effective and well-tolerable treatment
      for patients with BPH and LUTS, although further studies are needed to assess
      result durability and long-term efficacy.

PMID- 11306879
TI  - Is there a relationship between the amount of tissue removed at transurethral
      resection of the prostate and clinical improvement in benign prostatic
      hyperplasia.
AB  - OBJECTIVE: To assess in a prospective trial the influence of the amount of tissue
      resected at transurethral resection of the prostate (TURP) for benign prostatic
      enlargement on the symptom improvement as assessed by symptom scores. METHODS:
      Between December 1996 and August 1998 a total of 138 men (mean age 68.2, range 53
      89) with symptomatic benign prostatic enlargement who underwent TURP participated
      in this prospective study. Patients were assessed preoperatively with the
      International Prostate Symptom Score (IPSS), the American Urological Association
      Bother Score (AUA-BS) and the Benign Prostatic Hyperplasia Impact Index (BPH-II)
      as well as urinary flow rate measurements (Qmax) and prostate volume (PV) and
      residual urine determination by ultrasound. The amount of tissue resected was
      weighed. Patients were followed with reevaluation of Q(max), residual urine and
      the symptom and bother scores at 3 and 6 months. RESULTS: A close correlation
      between preoperative PV (mean 49.0 ml, SD 22.0, range 13-140) and the resected
      tissue weight (RTW, mean 24.7 g, SD 18.0, range 6-128) was seen (r = 0.75, p <
      0.001). Age was correlated with preoperative PV (r = 0.23, p < 0.05). While
      significant mean improvements in Q(max), residual volume and IPSS, AUA-BS and BPH
      II were found 3 and 6 months postoperatively, a negative correlation was seen
      between the RTW and the IPSS, the AUA-BS and the BPH-II 3 months after TURP (r = 
      0.23, p < 0.024; r = -0.23, p < 0.025; r = -0.20, p = 0.05). No statistically
      significant correlation was seen between symptom change and the percentage of PV
      removed or the residual prostatic weight. Classification of the patients into
      groups depending on preoperative PV (< 30, 31-50, 51-70 and >70 ml) showed a
      tendency for patients with larger PV to gain more symptom improvement
      postoperatively. CONCLUSIONS: Early symptom improvement after TURP will depend on
      the amount of tissue removed but the relationship is weak and affected by several
      other confounding factors. Apparently, the symptomatic improvement after TURP is
      not primarily dependent on the relative completeness of the resection. Patients
      with larger prostates and larger RTW tend to gain more symptomatic benefit from
      TURP than do patients with smaller prostates.

PMID- 11306880
TI  - Biochemical course after radical retropubic prostatectomy: preliminary results.
AB  - OBJECTIVE: To investigate prognostic factors in localized and lymphatically
      spread prostate cancer. METHODS: The biochemical course after radical retropubic
      prostatectomy in 306 patients was subject to a retrospective analysis. RESULTS:
      Prostate-specific antigen (PSA), Gleason score (prostatectomy specimen) and
      pathological stage proved to be prognostically relevant (p < 0.0001). PSA,
      Gleason score and tumor stage also were to be considered as (independent)
      prognostic factors by means of a multivariate analysis (p < 0.001), whereas
      perineural invasion (prostatectomy specimen) and preoperative bone marrow
      findings (CK 2) had no impact on the course of the disease. After a median follow
      up of 1,307 days (3.6 years), a biochemical relapse occurred in 41.8%.
      CONCLUSION: High preoperative PSA values and the resulting high portion of
      advanced tumor stages are a possible basis for the high biochemical relapse rate
      in our collective. The learning curves of several surgeons and the previously
      more restrictive pelvic lymphadenectomy (surgical understaging) may also be
      considered causes.

PMID- 11306881
TI  - Radiotherapy for PSA recurrence after radical prostatectomy.
AB  - OBJECTIVES: The treatment of patients presenting with an isolated PSA recurrence
      after radical prostatectomy (RP) remains controversial. The present study aims at
      assessing the results of salvage radiotherapy (RT), to define prognostic factors
      and to identify subgroups of patients most suitable for RT with curative intent.
      MATERIALS AND METHODS: A retrospective study was performed of 53 patients,
      diagnosed with a rising PSA after RP, and treated with RT to the prostate bed,
      between July 1992 and July 1998. RESULTS: On univariate analysis, significant
      determinants to obtain and maintain a nondetectable PSA (< 0.02 ng/ml) were
      Gleason grade (< or = III vs. < or = IV), pre-RT PSA, considered as categorical
      or continuous variable, and pathological stage, pT (2 vs. 3). Pre-RP PSA (< or =
      10 vs. >10), time interval between surgery and moment of rising PSA and
      pathological section margin status were not significant. On multivariate
      analysis, only Gleason grade and pre-RT PSA remained significant. For the patient
      group with a Gleason grade < or = III the PSA-free survival at 3 years was 75%
      (+/- 11%) compared to 27% (+/- 9%) for the patients with a Gleason grade > or =
      IV (p = 0.002). Pre-RT PSA significantly influenced PSA-free survival in the
      first group, but not in the latter. CONCLUSION: From the group of RP patients
      with rising PSA following a postsurgery PSA-free period, subgroups can be defined
      with a distinctly different probability of obtaining and maintaining
      nondetectable PSA levels after salvage RT.

PMID- 11306882
TI  - Differences in gene expression in muscle-invasive bladder cancer: a comparison of
      Italian and American patients.
AB  - OBJECTIVE: To seek differences in gene expression in the primary muscle-invasive
      bladder cancers of two cohorts of patients having different survival rates. An
      Italian group treated by transurethral resection of the bladder tumor (TURBT) and
      neo-adjuvant chemotherapy using methotrexate, vinblastine, adriamycin and
      cisplatin (M-VAC) followed by TURBT, partial cystectomy or radical cystectomy
      (75% 3-year survival) was compared to an American cohort treated by radical
      cystectomy (51% 3-year survival). METHODS: Immunohistochemistry was used to
      examine the protein expression levels of three genes that act at the G1/S cell
      cycle checkpoint, p53, p21/waf-1/cip1 (a downstream effector gene in the p53
      pathway) and Rb, plus a major inhibitor of apoptosis, Bcl-2. RESULTS: For the
      bladder cancers of the Italian patient cohort, there was a significantly higher
      rate of p53 immunopositivity (93 vs. 63%, p = 0.002) and a significantly lower
      rate of Rb loss (25 vs. 54%, p = 0.009). In bivariate analysis, 72% of Italian
      tumors were immunopositive for both p53 and p21 (p53+/p21+) vs. 49% for the
      American tumors. The subset of Italian patients with p53+/p21+ tumors were more
      frequently disease-free (stage pT0) following chemotherapy and were less likely
      to fail therapy than those with p53+/p21- tumors (p = 0.0357). Loss of Rb
      staining was associated with a decreased 5-year survival in the Italian, but not
      in the American patients. CONCLUSIONS: (1) Significant differences in the
      expression of the p53, p21 and Rb genes were found between the 2 groups of
      patients. (2) Italian patients with p53+/p21+ tumors had significantly lower
      recurrence rates after TURBT and chemotherapy than those having p53+/p21- tumors.
      (3) Absence of p21 immunopositivity in the Italian tumors may identify
      alterations in the p53 pathway that predict poor outcome.

PMID- 11306883
TI  - Prognostic significance of histopathological grading and immunoreactivity for p53
      and p21/WAF1 in grade 2 pTa transitional cell carcinoma of the urinary bladder.
AB  - OBJECTIVE: At present, there are no predictors of tumour behaviour for grade (G)
      2 pTa transitional cell carcinomas (TCC) of the bladder. Here we analyse the
      prognostic relevance of histopathological grading and the immunohistochemical
      detection of p53 and p21/WAF1. METHODS: 70 patients were newly diagnosed with G2
      pTa TCC of the bladder based on transurethral resection specimens. Two
      pathologists, blinded with respect to the clinical outcome, confirmed the initial
      grade and subclassified the G2 lesions into G2a and G2b carcinomas based on the
      degree of nuclear atypia and the number of mitoses. Immunoreactivity for p53 and
      p21/WAF1 was evaluated semiquantitatively. RESULTS: There were 52 G2a and 18 G2b
      tumours, mean follow-up was 49.2 months. Of all patients, 31.4% remained tumour
      free, 48.6% recurred with the same tumour grade and stage, and 20.0% showed
      tumour progression. Patients with G2a tumours developed tumour progression in 13%
      in contrast to 39% with G2b lesions (p = 0.037). Of 21 p53-positive tumours, 33%
      (7/21) developed progressive disease, whereas 14% (7/49) of p53-negative patients
      showed tumour progression (p = 0.102). Neither p21/WAF1 expression alone nor the
      combination of p53 and p21/WAF1 correlated with clinical outcome. CONCLUSION: The
      more detailed grading system but not p53 or p21/WAF1 immunohistochemistry was
      found to be an independent prognostic factor for tumour progression.

PMID- 11306884
TI  - Encrusted cystitis and pyelitis.
AB  - Encrusted cystitis (EC) and encrusted pyelitis (EP) are rare chronic inflammatory
      diseases of the bladder and renal pelvis, respectively, and are characterized by
      mucosal inflammation with deposits of ammonium magnesium phosphate on the
      urothelium. Corynebacterium urealyticum is the pathogen responsible in the vast
      majority of cases. We report 4 cases of EC and 1 case of EP. In 1 case of EC
      Ureaplasma urealyticum was isolated as the microorganism responsible. To the best
      of our knowledge, U. urealyticum-induced EC has never been reported previously.

PMID- 11306885
TI  - Effects of abdominal location and epididymal or vasal obstructions either
      individually or in association on ipsilateral and contralateral testes. A
      histologic and DNA flow cytometric analyses.
AB  - OBJECTIVE: An experimental study was conducted to evaluate the damages in
      ipsilateral and contralateral testes in individual or associated presences of
      abdominal location and vasal or epididymal obstructions. METHODS: Six groups each
      consisting of 8 rats were established. The groups included sham operation,
      ligation of the vas deferens, detachment of the epididymis from testis, abdominal
      placement of the testis, abdominal placement of the testis with vas deferens
      ligation, and abdominal placement of the testis with detachment of epididymis
      from testis. After 30 days, bilateral orchidectomy was performed. Mean
      seminiferous tubular diameters (MSTD) and mean testicular biopsy scores (MTBS)
      were obtained for each testis. Relative proportions of haploid, diploid and
      tetraploid cells were determined by DNA flow cytometry. MSTD, MTBS and the
      proportions of haploid cells were compared through one-way analysis of variance.
      RESULTS: While vas deferens ligation has diminished MSTD only in the
      contralateral testes, abdominal testis and detachment of epididymis have
      diminished MSTD in both ipsilateral and contralateral testes. MTBS were depressed
      only in the ipsilateral testes in groups of abdominal testis, vas deferens
      ligation and detachment of epdidymis. However, ratios of haploid DNA were
      depressed in both ipsilateral and contralateral testes. Abdominal testis together
      with vas ligation or detachment of epididymis has further depressed the ratios of
      haploid DNA in both ipsilateral and contralateral testes. CONCLUSION: Compared to
      their individual presence, the associated presence of abdominal testis and vasal
      or epididymal obstructions may augment the damages encountered within the
      ipsilateral and contralateral testes.

PMID- 11306886
TI  - Outcomes for surgical management of orchalgia in patients with identifiable
      intrascrotal lesions.
AB  - OBJECTIVE: The outcome of surgery for relief of orchalgia in patients with
      identifiable intrascrotal pathology is not well defined. We evaluated the success
      of commonly performed surgical procedure indicated for pain relief in patients
      with specific intrascrotal lesions. METHODS: Surgical cases performed for relief
      of painful scrotal pathology were reviewed, including ligation of internal
      spermatic vein, hydrocelectomy, spermatocelectomy, and orchiopexy for suspected
      intermittent torsion. Relief of pain as reported to the physician and time for
      return to full activity were determined. Pain relief was compared to a 50%
      placebo rate using Fisher's exact test. RESULTS: Eigthy-five of 151 patients
      (56%) undergoing surgery for pain relief had complete data and adequate follow-up
      for analysis. Of 40 patients who had ligation of the internal spermatic vein, 30
      (75%) were relieved of pain (p = 0.037). All 19 patients with painful hydroceles
      and 16 of 17 (94%) with spermatoceles were relieved of pain (p < 0.001). Of 9
      patients undergoing scrotal orchiopexy for suspected intermittent torsion, 8
      (89%) were pain-free (p < 0.001). CONCLUSION: Surgical management of specific
      intrascrotal lesions is highly effective.

PMID- 11306887
TI  - Unenhanced helical computed tomography in the evaluation of acute flank pain.
AB  - OBJECTIVE: The diagnostic value of unenhanced helical computed tomography (CT)
      for the evaluation of acute flank pain is investigated in a prospective study.
      PATIENTS AND METHODS: In 125 patients aged 18-86 years, we performed unenhanced
      helical CT in addition to abdominal plain film, abdominal ultrasound and
      urinalysis as a diagnostic measure for acute flank pain. Ureteral calculi were
      confirmed or, respectively, excluded by retrograde ureteropyelography in 80
      cases. In the other cases, diagnosis was verified by clinical course and/or stone
      asservation. RESULTS: In 91 of 125 patients the flank pain was caused by a
      ureteral calculus. In 67 of 91 patients with urolithiasis, stones could be
      collected for analysis. Helical CT was able to precisely identify 90 ureteral
      calculi. Abdominal plain films led to 8 false-positive and 48 false-negative
      findings. Thus, sensitivity of plain radiography, ultrasound and urinalysis was
      47, 11 and 84% with a specificity 76, 97 and 32%, respectively. CONCLUSIONS:
      Unenhanced helical CT reaches a distinctively increased diagnostic value
      (sensitivity 99%, specificity 97%) in the evaluation of acute flank pain as
      compared to plain radiography, ultrasound and urinalysis.

PMID- 11306888
TI  - Percutaneous suprapubic cystolithotripsy for pediatric bladder stones in a
      developing country.
AB  - OBJECTIVE: To evaluate our experience with percutaneous suprapubic
      cystolithotripsy (PCCL) in Yemeni children with endemic urinary bladder stones.
      PATIENTS AND METHODS: Between January 1993 and December 1998, 117 children
      underwent percutaneous suprapubic lithotripsy in Arabia Felix Modern Hospital,
      Sana'a Republic of Yemen. The patients' ages ranged from 8 months to 14 years
      (average 3.7 years). Ninety patients (77%) were under 5 years old; 20 patients
      (16%) were between 6 and 10 years old, and 7 patients (6%) were between 11 and 14
      years old. There were 116 boys and 1 girl. The stone size ranged from 0.7 to 4
      (average 2.3) cm. Five patients had coexisting urinary bilharziasis and another 5
      patients had coexisting renal stone. In 10 patients, the stone was in the
      urethra. The procedure was done under general anesthesia. Dilation of the tract
      was made under fluoroscopy. The instrument was an adult 26-french nephroscope,
      the same as that used for percutaneous nephrolithotripsy. Ultrasound
      disintegration was needed for stones of > 1 cm. A suprapubic catheter was left
      for 24 h, and a urethral catheter was kept for 48 h. RESULTS: All patients became
      stone free. The average operating time was 15 (5-50) min. The average hospital
      stay was 2.7 (2-5) days. No severe intra- or postoperative complication was
      observed. The nucleus and/or the main component of the stones were ammonium acid
      urate in 109 patients (93%). CONCLUSION: Based on our experience we can conclude
      that percutaneous suprapubic lithotripsy is a safe and effective method for the
      treatment of bladder stones in children. It reduces morbidity and hospital stay
      and thus the cost of treatment. Our series proves the nutritional etiology of
      endemic pediatric bladder stones. To our knowledge, this is the largest series
      reported on percutaneous suprapubic management of endemic bladder stones in
      children.

PMID- 11306889
TI  - Organ and species specificity in the stimulation of transitional epithelial cell
      growth by fibroblasts.
AB  - OBJECTIVES: Culture of transitional epithelium for urinary tract reconstruction
      has been problematic due, in part, to the dependence of urothelial cells on a
      basal layer of bladder fibroblasts for growth. In vitro studies on the effect of
      bladder, ureter, and intestinal fibroblast cocultures and conditioned media upon
      urothelial cell growth were conducted to better characterize the dependence of
      urothelial cells of fibroblasts. METHODS: Primary cultures of human and porcine
      bladder, ureter, and intestinal fibroblasts and bladder and ureter urothelial
      cells were established. The urothelial cells were incubated with fibroblasts in a
      coculture system and growth compared to that of individual fibroblast and
      urothelial cultures. Urothelium-specific medium was exposed to the fibroblast
      cultures for 6, 12, and 24 h. Urothelial cell growth in each of the fibroblast
      conditioned media was evaluated. RESULTS: Coculture of human urothelial cells
      with human bladder and ureter fibroblasts yielded increased cell growth when
      compared to the cells in individual culture. This improvement was greatest for
      the bladder fibroblasts in coculture with bladder epithelial cells. The media
      exposed to bladder and ureter fibroblasts for 24 h significantly increased
      bladder and ureter urothelial growth compared to fresh medium. Coculture with
      intestinal fibroblasts and exposure to intestinal fibroblast conditioned media
      did not significantly stimulate urothelial cell growth. Similarly, coculture and
      conditioned media studies of porcine urothelial cells with porcine bladder and
      ureter fibroblasts (but not intestinal fibroblasts) yielded increased cell growth
      when compared to the cells in individual culture, particularly with bladder
      fibroblasts. However, human urothelial cells were not stimulated by porcine
      bladder and ureter fibroblast conditioned media, nor were porcine urothelial
      cells stimulated by human bladder and ureter fibroblast conditioned media.
      CONCLUSIONS: The ability of urinary fibroblasts to stimulate urothelial cell
      proliferation resides in an unidentified soluble factor secreted into the medium,
      independent of the presence of the fibroblasts. This factor is relatively organ
      and species-specific.

PMID- 11306890
TI  - Interferon-alpha suppresses the antiapoptotic effect of NF-kB and sensitizes
      renal cell carcinoma cells in vitro to chemotherapeutic drugs.
AB  - BACKGROUND: Immunochemotherapy (ICT) with interleukin-2 (IL-2) and interferon
      alpha (IFNalpha) with a secondary effector (5-fluorouracil, 5 FU) is the only
      promising treatment for advanced renal cell carcinoma (RCC). With IFNalpha,
      besides the activation mechanisms of the immunosystem, a direct antitumor effect
      on tumor cells is expected. MATERIALS AND METHODS: NF-kB activity in three
      permanent cell lines (Hep2, HepG2, HT29) and in primary RCC cell lines was
      measured after incubation with tumor necrosis factor-alpha (TNFalpha), IFNalpha,
      IFN-gamma, TNFalpha+IFNalpha, and IFNgamma+TNFalpha, respectively. NF-kB activity
      and induction of apoptosis by chemotherapeutic drugs (5FU and doxorubicin) were
      determined in cells transfected with a constitutively active NF-kB p65 or a
      dominant negative IkB. RESULTS: NF-kB signaling induced by TNFalpha is suppressed
      by IFNalpha and IFNgamma in the permanent cell lines and in the primary RCC tumor
      cell cultures. In an in vitro ICT model we show that pretreatment of RCC with IL
      2 and IFNalpha leads to a diminished NF-kB response to TNFalpha. In certain
      tumors, this correlates with increased susceptibility to investigated
      chemotherapeutic drugs as shown by annexin stain and cell elimination. Modulation
      of the cellular NF-kB state by a constitutively active p65 or a dominant negative
      IkB mimics this effect. The IkB construct leads to the same effects as IL
      2/IFNalpha pretreatment as shown by predominant elimination of the transfected
      cells from the overall population, while introduction of p65 leads to a partial
      rescue from the effect of IL-2 and IFNalpha. The described effect, however,
      applies only to a selection of primary cell cultures. CONCLUSIONS: Besides the
      immunomodulation effects, treatment of RCC with IL-2/IFNalpha leads to a
      proapoptotic state in certain tumors. The relevant mediator seems to be IFNalpha
      by suppression of the antiapoptotic effect of NF-kB. These data can provide an
      experimental base for correlation with real patient outcome after ICT.

PMID- 11306891
TI  - Solitary fibrous tumour of the urinary bladder with expression of bcl-2, CD34,
      and insulin-like growth factor type II.
AB  - We describe a solitary fibrous tumour of the urinary bladder wall removed from a
      50-year-old man with a history of pelvic pain, dysuria, and urinary bleeding.
      Anamnesis revealed a weight increase during the preceding 3 months, but no
      apparent episodes of biochemical hypoglycaemia or hormonal abnormalities. The
      patient is alive and well 18 months after surgery. Pathological examination
      revealed a 6.5-cm well-circumscribed nodular mass composed of uniform spindle
      cells arranged in bundles and fascicles with varying amounts of collagen and a
      typical haemangiopericytoma-like vascular pattern. The tumour cells were positive
      for bcl-2, CD34, and vimentin and ultrastructurally showed mesenchymal
      myofibroblastic traits. These cells produced insulin-like growth factor type II
      mRNA as demonstrated by non-isotopic in situ hybridization. This rare case with a
      solitary fibrous tumor suggests that insulin-like growth factor type II could
      join CD34 and bcl-2 as markers for postoperative differential diagnosis.

PMID- 11306894
TI  - Long-term effects on BPH of medical and instrumental therapies.
AB  - A variety of methods are available that provide relief of lower urinary tract
      symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). This paper
      reviews approaches for assessing treatment outcomes, along with morbidity and
      long-term reintervention rates for different mechanical treatments. Symptom
      scores do not necessarily correlate with the severity of bladder outlet
      obstruction, whereas reintervention rates provide a reliable objective measure of
      long-term outcomes. Less invasive procedures, such as transurethral needle
      ablation (TUNA) and transurethral microwave therapy (TUMT), have lower rates of
      haemorrhage than transurethral resection of the prostate (TURP) and transurethral
      vaporisation of the prostate (TUVP), and retrograde ejaculation is not seen after
      TUNA. Reintervention rates are generally low with such treatments, and appear to
      be lower for TURP than for thermotherapy and TUNA. In contrast, the secondary
      intervention rate for contact laser prostatectomy increases with time after
      treatment. It can be concluded that the treatment of BPH should be individualised
      according to patient's needs. The staged approach of medical therapy, followed by
      thermotherapy, then TURP, is the best approach to minimise the negative impact of
      LUTS on quality of life.

PMID- 11306895
TI  - Does acute urinary retention respond to alpha-blockers alone?
AB  - Studies show that men who undergo prostatectomy after acute urinary retention
      (AUR) are at increased risk of intraoperative complications, transfusions,
      postoperative complications and hospital death. Urethral catheterisation for AUR
      has also been shown to result in bacterial colonization at a rate of 4% per day.
      Consequently, it is preferable that patients undergo a trial without catheter
      (TWOC) after an episode of AUR to potentially avoid surgery altogether, or to
      avoid having a urinary catheter in situ even if they do come to prostatectomy. A
      number of small studies indicate that alpha(1) blockers may improve the success
      rate of a TWOC. A placebo-controlled TWOC study of alfuzosin in 81 patients with
      AUR shows that a successful TWOC was achieved in 55% of alfuzosin-treated
      patients compared with 29% in the placebo group (p = 0.03). Long-term follow-up
      suggest that 32% (11/34; 22 treated with alfuzosin and 12 with placebo) of the
      patients had a further episode of AUR at a mean of 4.1 months following their
      first episode. This shows that there is a window of opportunity for surgical
      intervention prior to the occurrence of a second episode of AUR. Patients who had
      a subsequent episode of AUR or who needed surgery were found to have a higher
      post-void residual (PVR) urine following their successful TWOC, and thus may be
      identified as candidates for close follow-up and early intervention. As alfuzosin
      has been shown to reduce PVR, this factor may help prevent recurrent retention
      following TWOC.

PMID- 11306896
TI  - Do alpha-blockers prevent the occurrence of acute urinary retention?
AB  - Acute urinary retention (AUR) is a common complication of benign prostatic
      hyperplasia (BPH) and the incidence varies widely from 0.4 to 25% per year in men
      seen in urology practices. It has been estimated that AUR is the indication for
      surgery in around 25-30% of patients undergoing transurethral resection of the
      prostate (TURP) and that emergency TURP for AUR is associated with greater
      morbidity than elective TURP. Risk factors for AUR include lower urinary tract
      symptoms (LUTS), depressed peak urinary flow rate, enlarged prostate, high
      postvoid residual (PVR) urine and old age. Alfuzosin has been shown to
      significantly increase maximum flow rate and relieve bladder outlet obstruction,
      resulting in a reduction in PVR urine. A pooled analysis of 11 placebo-controlled
      studies involving 1,470 patients with LUTS suggestive of BPH indicates that
      significantly greater improvements were observed in patients treated with
      alfuzosin than with placebo. A 6-month placebo controlled study of 518 patients
      reported a 0.4% incidence of AUR in the alfuzosin group compared with a 2.4%
      incidence with placebo (p = 0.04). These positive effects on PVR could be related
      to the reduction in incidence of AUR seen in alfuzosin-treated patients.

PMID- 11306897
TI  - The efficacy and safety of a new once-a-day formulation of an alpha-blocker.
AB  - OBJECTIVES: To assess the long-term efficacy and safety of alfuzosin 10 mg OD in
      patients with symptomatic BPH. METHODS: Patients (>50 years) were randomised to
      alfuzosin 10 mg OD, alfuzosin 2.5. mg t.i.d. or placebo for 3 months. Open-label
      alfuzosin 10 mg OD was continued for up to 1 year. Efficacy assessments included
      the International Prostate Symptom Score (I-PSS) and quality of life index and
      uroflowmetry. RESULTS: At 3 months, there was a significant reduction in I-PSS
      and a significant improvement in peak flow rate for both alfuzosin groups
      compared with placebo (p < 0.05). Vasodilatory adverse experiences were more
      common in the alfuzosin 2.5 mg group than the 10 mg OD group. Improvements in
      symptoms and flow rate with alfuzosin 10 mg OD were maintained for up to 12
      months. CONCLUSION: Alfuzosin 10 mg OD is an effective treatment for symptomatic
      BPH for at least 12 months, with a better cardiovascular safety profile than the
      immediate release formulation.

PMID- 11306898
TI  - Lipid peroxidation and antioxidant status in maternal and cord blood.
AB  - The present study was undertaken to determine the change of blood lipid peroxide
      and antioxidant status in healthy nonpregnant women (n = 20), pregnant women in
      the third trimester (n = 20), pregnant women during delivery (n = 26) and fetal
      cord blood. Plasma and erythrocyte malondialdehyde (MDA) levels were found to be
      significantly higher and erythrocyte glutathione (GSH) levels were significantly
      lower in pregnant women in the third trimester than in nonpregnant women (p <
      0.02, p < 0.03 and p < 0.001, respectively). The highest plasma and erythrocyte
      MDA levels and the lowest GSH levels were obtained from the pregnant women during
      delivery (6.99 +/- 2.35 nmol/ml, 283.20 +/- 43.81 nmol/g Hb, 6.73 +/- 2.34
      micromol/g Hb, respectively). Erythrocyte glutathione peroxidase (GSH-P) and
      glutathione reductase (GSH-R) activities were not different between the groups.
      Maternal plasma and erythrocyte MDA levels were significantly correlated with
      cord blood plasma and erythrocyte MDA levels (r = 0.63, p < 0.001, and r = 0.41,
      p < 0.001, respectively). There was a significant positive correlation in GSH-R
      and in GSH-P activities between maternal and cord blood erythrocytes (r = 0.81, p
      < 0.001, and r = 0.79, p < 0.001, respectively). A significant correlation was
      found between maternal erythrocyte GSH-P and both cord blood erythrocyte GSH-R
      activities (r = 0.74, p < 0.001) and cord erythrocyte GSH levels (r = 0.73, p <
      0.001). There was also a significant negative correlation between maternal
      erythrocyte MDA and cord erythrocyte GSH-R levels (r = -0.9, p < 0.001). Our
      results suggest that lipid peroxidation and antioxidant status may be changed
      during delivery, and these changes may affect the fetus by creating oxidative
      stress.

PMID- 11306899
TI  - Erythropoietin in the treatment of iron deficiency anemia during pregnancy.
AB  - The aim of this study was to investigate the efficacy of recombinant human
      erythropoietin (rHuEPO) combined with parenteral iron, in the treatment of
      moderate and severe iron deficiency anemia during pregnancy. Twenty-six pregnant
      women, who had been ineffectively treated with iron supplementation alone for at
      least 8 weeks, were enrolled. They met the following criteria for inclusion in
      the study: hemoglobin (Hb) concentration <8.5 g/dl, evidence of iron deficiency
      anemia, and absence of other pregnancy complications, or severe systemic
      diseases. The treatment protocol comprised of a combination therapy with 150
      IU/kg rHuEPO subcutaneously three times per week and 100 mg parenteral iron
      daily, for a total period of 4 weeks. Nineteen out of 26 women (73%) showed a
      quick response, with Hb reaching normal levels within the first 2 weeks of
      treatment. They displayed an average of 3.17 g/dl increase in Hb concentration
      during the total period of therapy, with 3.0 g/dl increase within the first 2
      weeks. In 5 women (19.2%) there was no significant increase in Hb levels, while
      in 2 women (7.6%) a further decline in Hb concentration was observed, that
      necessitated a blood transfusion. In conclusion, rHuEPO combined with parenteral
      iron is an effective treatment for moderate and severe iron deficiency anemia
      during pregnancy, with minimal adverse or side effects. It may serve as an
      alternative to blood transfusion, or in cases of resistant anemia that are not
      effectively treated by iron supplementation alone. However, further studies are
      needed to investigate the poor response observed in about 25% of treated
      patients.

PMID- 11306900
TI  - Fetal circulatory responses to maternal blood loss.
AB  - We examined the fetal circulatory responses to maternal blood loss in pregnant
      women during the third trimester. Seven healthy women with placenta previa and
      singleton pregnancies underwent phlebotomies in an autologous donation program.
      Four hundred milliliters of blood was collected within 15 min at 34 and 35 weeks
      of gestation. Continuous electric recordings of fetal heart rate were performed
      during the first blood collection, and the maternal uterine artery (UtA),
      umbilical artery (UmA) and fetal middle cerebral artery (MCA) Doppler velocity
      waveforms were recorded before, immediately after and 24 h after the second
      collection in each patient. The average fetal heart rate, maternal UtA and UmA
      pulsatility indices did not change measurably during or after maternal blood
      collections. However, the average fetal MCA pulsatility index decreased
      significantly 24 h after maternal blood loss. The observation of a decrease in
      fetal MCA pulsatility index may indicate delayed fetal asphyxia following mild
      maternal hemorrhage.

PMID- 11306901
TI  - Maternal and paternal family history of diabetes in women with gestational
      diabetes or insulin-dependent diabetes mellitus type I.
AB  - Animal studies have shown that prenatal exposure to a diabetic intrauterine
      milieu leads to an increased risk in the female offspring of developing
      gestational diabetes (GD). In the present study, the family history of non
      insulin-dependent diabetes mellitus type II (NIDDM) and insulin-dependent
      diabetes mellitus type I (IDDM) was evaluated in 106 women with GD, as compared
      to 189 women with IDDM. In GD patients, the prevalence of diabetes was
      significantly greater in mothers than in fathers (p = 0.03). This was mainly due
      to a greater prevalence of NIDDM in the mothers (p = 0.05). Furthermore, a
      significant aggregation of NIDDM was also observed in the maternal-grandmaternal
      line of GD women, as compared to the paternal-grandpaternal side (p = 0.02). In
      patients with IDDM no significant difference concerning the prevalence of any
      type of diabetes between mothers and fathers was observed. In conclusion, an
      aggregation of NIDDM in mothers and grandmothers of women with GD is reported
      here. A history of NIDDM on the maternal side of pregnant women should be
      considered as a particular risk factor for GD and, hence, for intergenerative
      transmission of NIDDM, which therefore might be prevented, at least in part, by
      strict avoidance of GD.

PMID- 11306902
TI  - Elevated interleukin-8 concentrations in cervical secretions are associated with
      preterm labour.
AB  - The aim of this study was to assess the potential clinical utility of interleukin
      8 (IL-8) present in cervical secretions as a marker of preterm labour and
      delivery. Samples of cervical mucus from 91 pregnant women were assessed for the
      presence and concentration of IL-8. Two samples were collected (at 18 +/- 2 and
      28 +/- 2.5 weeks of gestation) and correlated with cervicovaginal microbiology
      and cervical length, as measured by transvaginal ultrasound. The IL-8
      concentration at 28/40 was significantly higher in women who went on to deliver
      preterm (p < 0.01), and there was a greater than five-fold increase from 18 to 28
      weeks in 6/7 of these women.

PMID- 11306903
TI  - Relation between serum uric acid and plasma adenosine levels in women with
      preeclampsia.
AB  - The aim of this study was to examine the relationship between plasma adenosine
      and serum uric acid levels in women with preeclampsia. Maternal arterial blood
      sampling was performed to measure serum uric acid and plasma adenosine levels in
      20 pregnant women complicated by preeclampsia and 22 normal pregnant women at 33
      38 weeks of gestation. The average plasma adenosine levels were 0.31 +/- 0.12
      micromol/l in the normal pregnant group and 0.45 +/- 0.11 micromol/l in the
      preeclampsia group. The mean serum uric acid level in women with preeclampsia was
      5.9 +/- 0.60 mg/dl, significantly higher than in the normal pregnant women (4.4
      +/- 0.69 mg/dl). Positive correlations were found between serum uric acid and
      plasma adenosine levels in both the group with (r(2) = 0.38, p < 0.05) and the
      group without (r(2) = 0.54, p < 0.05) preeclampsia. There was also a significant
      correlation between serum uric acid and plasma adenosine levels on the whole
      (r(2) = 0.59, p < 0.05). Our results suggest that increased adenosine is a
      contributing source of preeclamptic hyperuricemia.

PMID- 11306904
TI  - Umbilical artery pulsatility index in pregnancies complicated by insulin
      dependent diabetes mellitus without hypertension.
AB  - OBJECTIVE: In a group of diabetic pregnant women, the umbilical artery
      pulsatility index (PI) was compared with both pregnancy complications and
      perinatal outcomes. METHOD: We evaluated 67 women with pregnancies complicated by
      insulin-dependent diabetes mellitus (IDDM), without hypertension. For the study
      we took the last umbilical PI value before delivery into consideration. Doppler
      results were not used for patient management. Umbilical artery PI was correlated
      with the route of delivery and the following perinatal complications:
      intrauterine growth retardation; cesarean sections for acute fetal distress;
      respiratory distress syndrome (RDS); neonatal hyperbilirubinemia; hypocalcemia;
      hypoglycemia; macrosomia, and neonatal intensive care unit (NICU). RESULTS: Among
      the 67 diabetic patients enrolled in this study, 44 (66%) had umbilical PIs
      ranging from the 5th to the 95th percentile (PI mean +/- SD = 1.2 +/- 0.3), while
      23 (34%) had PIs above the 95th percentile (PI mean +/- SD = 1.6 +/- 0.3). Among
      the group with pathologic umbilical PIs, analysis of the data revealed a
      significantly higher incidence of both cesarean sections for acute fetal distress
      and perinatal complications: RDS; hyperbilirubinemia; hypoglycemia, and the need
      for NICU, respectively. CONCLUSION: In 34% of the diabetic pregnant women without
      hypertension, we found increased vascular resistances. Among these patients the
      incidence of perinatal complications was higher, and both closer maternal
      metabolic control and stricter care of fetal conditions are needed.

PMID- 11306905
TI  - Effect of heparin on activated partial thromboplastin time in patients undergoing
      gynecologic or obstetric surgery.
AB  - The exaggerated prolongation of the activated partial thromboplastin time (APTT)
      by heparin prophylaxis for postoperative thromboembolism may cause bleeding
      complications. We examined the effects of various doses of unfractionated heparin
      on the APTT in patients who underwent a gynecologic or obstetric operation. A
      total of 68 patients who underwent a gynecologic operation (n = 47) or a cesarean
      section (n = 21) with risk factors for thromboembolism received a continuous
      intravenous infusion of unfractionated heparin (110-285 IU/kg/day) after surgery
      until the patient was mobilized the next day. A group of 61 postoperative
      patients who did not receive heparin served as controls. The APTT was measured in
      these 129 patients preoperatively and on postoperative day 1. A clinical deep
      vein thrombosis occurred in only 1 patient, who was in the control group. No
      bleeding complications occurred in any patient. The percent change in the APTT
      was significantly correlated with the dose of heparin administered (p < 0.001).
      Compared with the control group, the mean APTT was not prolonged in the patients
      who received heparin at 110-149 IU/kg/day. It was prolonged significantly in the
      patients who received heparin at greater than 150 IU/kg/day. An exaggerated
      prolongation of the APTT, defined as an APTT greater than 150% of the
      preoperative value, was found in 0 of 32 patients in the 110-149 IU/kg/day group,
      1 of 28 patients (3.6%) in the 150-199 IU/kg/day group and 2 of 8 patients (25%)
      in the 200-285 IU/kg/day group. The continuous postoperative administration of
      intravenous heparin at less than 200 IU/kg/day does not result in an exaggerated
      prolongation of the APTT.

PMID- 11306906
TI  - Combined tension-free vaginal tape and prolapse repair under local anaesthesia in
      patients with symptoms of both urinary incontinence and prolapse.
AB  - OBJECTIVE: To study the combination of tension-free vaginal tape (TVT) and
      prolapse repair under local anaesthesia in patients suffering from stress
      incontinence and prolapse. STUDY DESIGN: The study was designed as a prospective,
      open, nonrandomized study. A standardized protocol was used for pre- and
      postoperative evaluation. Check-ups were performed after 2, 6, 12 and 24 months.
      The protocol included medical history, stress test (supine and standing position
      with a comfortably filled bladder), life quality assessment including a visual
      analogue scale, 24- to 48-hour pad test, and 48-hour micturition diary. PATIENTS:
      In total 32 patients participated. All suffered from urinary stress incontinence
      (grade 1-3) and prolapse (grade 1-3). 2 patients had previously undergone surgery
      2 and 3 times, respectively, for urinary incontinence with methods other than TVT
      (traditional anti-incontinence surgery). 3 patients had a history of total
      hysterectomy. 1 patient had a large rectocele with urinary and faecal
      incontinence. Mean age was 54 (range 31-74) years, mean parity 2 (range 0-5), and
      mean duration of incontinence 13 (range 2-29) years. SURGICAL TECHNIQUE: TVT was
      carried out according to the standardized technique as originally described. The
      prolapse repair included anterior and/or posterior colporrhaphy. All operations
      could be performed under local anaesthesia. RESULTS: 30 of 32 patients (93%) were
      cured. One patient (3%) was considerably improved, and 1 patient (3%) was
      considered a failure. Mean urinary leakage in 24 h was 96 (range 12-355) g
      preoperatively, and postoperatively 2.7 (range 0-28) g. Mean intraoperative
      bleeding was 75 (range 25-300) ml. Mean residual urine preoperatively was 15
      (range 0-85) ml, and postoperatively 7 (range 0-40) ml. The mean stay in hospital
      after surgery was 2 (range 1-5) days. No postoperative urinary retention, no
      defective healing, and no tape rejection occurred. There was one uneventful
      bladder perforation in a patient who had previously undergone traditional
      incontinence surgery. This patient left the hospital the day after surgery
      without postoperative catheterization. CONCLUSION: The study clearly demonstrates
      that TVT can be combined with prolapse surgery to effectively treat symptoms of
      prolapse and urinary stress incontinence.

PMID- 11306907
TI  - Pudendal nerve terminal motor latency in women with genuine stress incontinence
      and prolapse.
AB  - The aim of this study was to investigate changes in pudendal nerve terminal motor
      latency (PNTML) time in women with genuine stress incontinence (GSI) and with or
      without prolapse, in conjunction with measurement of maximal urethral closure
      pressure (MUCP). Eighty-five patients participated in the study and they were
      allocated to one of four groups, including the control group. A statistically
      significant difference was found in the PNTML time between patients with GSI and
      patients of the control group. The conduction time in patients with prolapse but
      no GSI did not show a statistically significant difference compared to the
      patients of the control group. The MUCP was reduced in patients with GSI, but no
      cutoff value of MUCP, which is pathognomonic of GSI, could be identified. We
      conclude that GSI is associated with a prolongation of PNTML time and a reduction
      in MUCP.

PMID- 11306908
TI  - Differential regulation of protein kinase C isoforms in human uterine leiomyoma.
AB  - The protein kinase C (PKC) isoenzyme expression pattern in human uterine
      leiomyoma was compared with that obtained in homologous myometrium distal from
      the tumor. The six PKC isoforms (PKCalpha, PKCbeta1, PKCbeta2, PKCdelta,
      PKCepsilon and PKCzeta) evidenced in the myometrium were found to be similarly
      expressed in leiomyoma. Quantitative immunoblotting revealed that all PKC
      isoforms were preferentially localized in the particulate fraction. To gain
      insight into the possible functional consequences of PKC expression patterns,
      subcellular redistribution in response to the mitogenic peptide endothelin-1 (ET
      1) was studied. After stimulation with ET-1, differential redistribution occurred
      in leiomyoma and myometrium, suggesting a selective role of PKC isoforms in the
      myometrial growth process.

PMID- 11306909
TI  - Effect of p53 polymorphism on the susceptibility of cervical cancer.
AB  - Using PCR amplification followed by confirmation with BstU I restriction enzyme
      digestion, the p53 Pro sequence was determined in tissues from 88 normal
      cervices, in 184 cervical swabs with mildly abnormal Pap smear, in 50 squamous
      cell cervical carcinoma specimens, and in 30 cervical adenocarcinoma samples. The
      frequencies for homozygous proline (Pro-72), homozygous arginine (Arg-72), and
      heterozygous proline/arginine (Pro/Arg-72) were 23% (n = 20), 28% (n = 25), and
      49% (n = 43), respectively, in normal cervices; 24% (n = 45), 28% (n = 51), and
      48% (n = 88), respectively, in samples with mild dyskaryotic changes in Pap
      smears; 26% (n = 13), 28% (n = 14), and 46% (n = 23), respectively, in squamous
      cell carcinomas, and 33.3% (n = 26), 46.2% (n = 36), and 20.5% (n = 16),
      respectively, in adenocarcinomas. In the present study, we have found that p53
      polymorphism may have a role in the development of adenocarcinoma but not
      squamous cell carcinoma. The arginine-encoding allele may thus be an important
      factor affecting host susceptibility to the development of adenocarcinoma.

PMID- 11306911
TI  - Neonatal vaginal prolapse.
AB  - We present an unusual case of neonatal vaginal prolapse in a term newborn and
      review the literature pertaining to this rare condition.

PMID- 11306910
TI  - Clinical and prognostic significance of human papillomavirus in a Chinese
      population of cervical cancers.
AB  - OBJECTIVE: To investigate the clinical and prognostic significance of human
      papillomavirus (HPV) in a Chinese population of cervical cancers. METHODS: We
      studied 121 cervical cancer tissue samples from patients treated at our hospital.
      Identification and typing of HPV were done by polymerase chain reaction (PCR)
      using consensus primers MY11 and MY09 followed by direct DNA sequencing. The
      results were correlated with various clinical and prognostic parameters. RESULTS:
      We found HPV DNA in 95 (78.5%) cases, including HPV-16 in 59 (48.8%) and HPV-18
      in 14 (11.6%) cases. chi(2) analysis revealed no significant correlation between
      the presence of HPV DNA and age at diagnosis, clinical stage, histologic type,
      tumor grading, 2-year and 5-year survival rate. Of the factors evaluated, age at
      diagnosis and histologic type were found to have a statistically significant
      relationship with HPV type. The mean age of the HPV-18 group was 48.6 years
      compared to 57.1 years for the HPV-16 group (p = 0.045) and 58.2 years for the
      HPV-negative group (p = 0.04). HPV-18 was detected more often in adenocarcinomas
      (AC) than in squamous cell carcinomas (SCC). Conversely HPV-16 was detected
      significantly more often in SCC (p < 0.0001). The HPV-negative group also had a
      higher incidence of SCC (p = 0.007). HPV-18-positive patients seemed to have more
      nodal involvement than both HPV-16-positive patients (45.5 vs. 20.8%) and HPV
      negative patients (45.5 vs. 18.2%); however, it did not reach statistical
      significance. CONCLUSIONS: These observations suggest that the presence of HPV
      DNA does not bear any clinical or prognostic significance in a Chinese population
      of cervical cancers. HPV-18 is found more often in younger patients and is
      associated with AC.

PMID- 11306912
TI  - Carney complex--an unexpected finding during puerperium.
AB  - Carney complex is an extremely rare, autosomal dominant, multi-system disorder
      characterized by multiple neoplasias and lentiginosis. The genetic defect
      responsible for this complex has been localized to the short arm of chromosome 2
      (2p16). The most prevalent clinical manifestations in patients with Carney
      complex are spotty skin pigmentation, skin and cardiac myxomas, Cushing's
      syndrome and acromegaly. Here we report the case of a 31-year-old woman with a
      spontaneous pregnancy. At 32 weeks of gestation, she was admitted to our
      Department of Obstetrics with hypertension and severe back pain. In addition, she
      had unusual pigmentation and typical cushingoid features. One day after
      admission, the pregnancy was terminated by emergency cesarian section because of
      preeclampsia and pathological CTG. During the postoperative period the severe
      back pain persisted, and radiographic evaluation revealed a collapse of L(2)/L(3)
      with severe osteopenia. A CT scan showed a mass in the right suprarenal area.
      Histopathological examination revealed a primary pigmented nodular adrenocortical
      disease. After biochemical confirmation of the diagnosis of Cushing's syndrome,
      it was recognized that the patient met the diagnostic criteria for Carney
      complex.

PMID- 11306913
TI  - Assisted reproductive technologies in conjunction with conservatively treated
      endometrial adenocarcinoma. A case report.
AB  - This case report illustrates the successful use of assisted reproductive
      technologies (ARTs) in a patient receiving conservative treatment for endometrial
      adenocarcinoma. A 31-year-old infertile woman, diagnosed as FIGO stage Ia
      endometrial adenocarcinoma (grade 1), received oral medroxyprogesterone acetate
      400 mg/day for 12 weeks. Endometrial curettage was performed and the absence of
      endometrial carcinoma was confirmed. A single pregnancy was achieved with in
      vitro fertilization and embryo transfer. A healthy female infant was born via
      cesarean section at 42 weeks' gestation. The carcinoma has not recurred, and the
      patient now desires a second child. We conclude that ART combined with
      progesterone treatment might be a powerful option for the treatment of infertile
      patients with early stage, well-differentiated endometrial adenocarcinoma.

PMID- 11306914
TI  - Vaccine strategies against schistosomiasis: from concepts to clinical trials.
AB  - Schistosomiasis, the second major parasitic disease in the world after malaria,
      affects 200 million people. Vaccine strategies represent an essential component
      of the control of this chronic debilitating disease where the deposition of
      millions of eggs in the tissues is the main cause of pathology. Research
      developed in our laboratory over the last 20 years has led to the identification
      of novel effector mechanisms, pointing for the first time to the protective role
      of Th2 responses and of IgE antibodies now supported by seven studies in human
      populations. The identification and molecular cloning of a target antigen, a
      glutathione S-transferase (GST), has made it possible to demonstrate its vaccine
      potential in several animal species (rodents, cattle, primates) and to establish
      consistently the capacity of vaccination to reduce female worm fecundity and egg
      viability through the production of neutralizing antibodies (IgA and IgG).
      Following promising preclinical studies, clinical trials (phase I and II) have
      been undertaken using Schistosoma haematobium GST, Sh28GST. High titers of
      neutralizing antibodies were produced (IgG3 and IgA) together with Th2 cytokines,
      consistently with the concepts developed from experimental models. With these
      results we are on the way towards a feasible approach of vaccine development
      against a major human parasitic disease.

PMID- 11306915
TI  - Mutant mice: a useful tool for studying the development of mast cells.
AB  - We have used various mouse mutants for studying the development of mast cells.
      The bone marrow origin of mast cells was shown by using giant granules of beige
      mice as a marker. Mast cell-deficient W/W(v) and Sl/Sl(d) mice are useful for
      investigation of the developmental processes. The mi locus encodes a member of
      the basic helix-loop-helix-leucine zipper protein family of transcription factors
      (MITF), and mast cells of mi/mi mice showed phenotypic abnormalities. Mast cells
      of mi/mi mice synthesized the mutant mi-MITF in normal amounts, and mi-MITF
      showed an inhibitory effect on the transcription of various mast cell-specific
      genes. On the other hand, mice of tg/tg possess the transgene insertional
      mutation in the 5' flanking region of the mi gene and do not express any MITFs.
      Genes whose transcription was suppressed were more numerous in mast cells of
      mi/mi mice than in those of tg/tg mice. The comparison between phenotypes of
      mi/mi mast cells and those of tg/tg mast cells gave some insights into the
      regulation of mast cell phenotypes by transcription factors.

PMID- 11306916
TI  - The monocyte/IgE connection: may polymorphisms in the CD14 gene teach us about
      IgE regulation?
AB  - BACKGROUND: Total IgE levels are known to be under genetic control. Linkage
      studies have indicated that one or more loci on chromosome 5q may control total
      IgE, as well as asthma and bronchial hyperresponsiveness to nonspecific stimuli.
      Our group has undertaken a systematic analysis of chromosome 5q, and has recently
      characterized five single nucleotide polymorphisms at position -1619, -1359, 
      1145, -809 and -159 in the promoter of the gene encoding CD14, the myeloid
      pattern recognition receptor that is critical for efficient innate immune
      response to lipopolysaccharide (LPS) and bacterial ligands. METHODS: Carriers of
      the major CD14 haplotypes were analyzed for serum levels of IgE and soluble CD14.
      In vitro IgE synthesis was assessed in peripheral blood mononuclear cells
      stimulated with IL-4 in the presence or absence of LPS or anti-CD14 monoclonal
      antibodies. RESULTS: An inverse correlation was found between serum levels of IgE
      and soluble CD14. On the other hand, in vitro IL-4-dependent IgE synthesis was
      strongly upregulated by LPS, but suppressed by anti-CD14 monoclonal antibodies.
      CONCLUSION: Our results highlight the complex role played by monocytes in IgE
      regulation.

PMID- 11306917
TI  - Enu mouse mutagenesis: generation of mouse mutants with aberrant plasma IgE
      levels.
AB  - BACKGROUND: The ENU Mouse Mutagenesis Project aims at a large-scale, systematic
      production of mouse mutants using the alkylating agent ethyl-nitrosourea (ENU).
      Offspring of mutagenized mice are subjected to a multiparameter screen to detect
      alterations in various phenotypes with the ultimate goal of identifying novel
      genes relevant for the expression of the phenotype. Using this approach, we have
      analyzed plasma IgE concentrations to identify mouse mutants with aberrant plasma
      IgE levels. METHODS AND RESULTS: ENU-mutagenized male C3HeB/FeJ were mated to
      wild-type females to produce F1 offspring. F1 animals were analyzed for
      alterations in their plasma IgE concentrations that showed a dominant mode of
      inheritance, or bred further to screen for recessive phenotypes. Plasma IgE
      concentrations were determined by ELISA and a normal range for plasma IgE was
      established using C3HeB/FeJ wild-type animals. So far we have tested 6568 F1
      animals. Repeated testing confirmed a stable aberrant IgE phenotype in 124
      animals. To confirm the genetic basis of the observed phenotype, these mice were
      subjected to confirmation crossing. Currently we have established 9 independent
      mutant mouse lines (3 with high plasma IgE and 6 with plasma IgE below detection
      limit) that have been genetically confirmed and additional 24 variant mouse lines
      are currently undergoing confirmation testing. CONCLUSION: ENU mouse mutagenesis
      allowed us to generate and identify mouse mutants with aberrant plasma IgE
      levels, which may be used to characterize novel genes involved in IgE regulation
      and may serve as animal models for IgE-mediated diseases.

PMID- 11306918
TI  - Promiscuous use of light chains by human IgE antibodies specific for three major
      grass pollen allergens.

PMID- 11306919
TI  - The IgE antigen receptor: a key regulator for the production of IgE antibodies.
AB  - Immunoglobulins in general form a substantial component of serum proteins, and
      play a role in homeostatic mechanisms, a first line of defense against pathogenic
      organisms and in immunological memory. In the secreted form, immunoglobulins
      represent the effector arm of the humoral immune system. However, immunoglobulins
      are not only secreted, but can also be expressed on the surface of a B lymphocyte
      (membrane immunoglobulin), and, in this physical state, most likely convey
      signals to steer the B cell along its differentiation pathway. A step forward in
      the understanding of the role of membrane immunoglobulins other than membrane IgM
      or IgD was achieved with two mouse lines with mutations in the epsilon heavy
      chain gene. In IgE(DeltaM1M2) mice serum IgE is reduced to less than 10% of
      normal mice, while IgE(KVKDeltatail) mice show a reduction of 50%, reflecting a
      serious impairment of the IgE-mediated immune response. We think that the
      cytoplasmic tail of IgE is involved in a signal transduction which leads to the
      expression of high quantities and qualities of secreted IgE immunoglobulins.

PMID- 11306920
TI  - Unexpected functions of FcepsilonRI on antigen-presenting cells.
AB  - In contrast to mast cells and basophils, the high affinity IgE receptor
      (FcepsilonRI) on antigen-presenting cells (APC) shows structural and functional
      differences. It consists only of a minimal structure of one alpha- and two gamma
      chains and enables APC to efficiently take up and present antigen in IgE-mediated
      delayed-type hypersensitivity reactions that are thought to play a pivotal role
      in atopic diseases. However, recent studies of FcepsilonRI signal transduction
      and function on APC suggest additional mechanisms by which FcepsilonRI engagement
      on APC could affect inflammatory reactions. FcepsilonRI ligation is able to
      induce major signaling events like protein tyrosine kinase activation including
      p72(syk) leading to PLC-gamma1 phosphorylation and consecutive calcium influx.
      Late signaling events like the activation of transcription factors such as NF
      kappaB provide a link to the release of proinflammatory cytokines and chemokines,
      Th-polarizing factors such as IL-12 and the induction of antiapoptotic factors.
      FcepsilonRI-mediated IL-10 production in monocytes could also influence their
      differentiation. Since there are hints that in vivo a functional FcepsilonRI
      signaling pathway only exists in individuals from an atopic background, we
      suggest that these unexpected mechanisms may have an effect on inflammatory
      reactions in atopic diseases.

PMID- 11306921
TI  - The role of alpha-galactosylceramide-activated Valpha14 natural killer T cells in
      the regulation of Th2 cell differentiation.
AB  - Valpha14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN
      gamma upon stimulation with a ligand, alpha-galactosylceramide (alpha-GalCer),
      and play a crucial role in various immune responses, including allergic diseases.
      Interestingly, Valpha14 NKT cells are not essential for the induction of IgE
      responses but rather induce suppression of specific IgE production upon
      activation. The suppression in the IgE production is not detected either in
      Valpha14 NKT cell-deficient mice or in IFN-gamma-deficient mice. Thus, activated
      Valpha14 NKT cells are likely to exert a potent suppressive activity on Th2 cell
      differentiation and subsequent IgE production by producing a large amount of IFN
      gamma. In marked contrast, little regulatory effect of IL-4 produced by Valpha14
      NKT cells on Th2 cell differentiation is suggested.

PMID- 11306922
TI  - Tapping allergen repertoires by advanced cloning technologies.
AB  - BACKGROUND: Complex allergenic sources such as moulds, foods and mites contain
      complex panels of IgE-binding molecules which need to be cloned, produced and
      characterized in order to mimic the entire allergenicity of whole extracts
      reconstituted by mixing single standardized recombinant allergens. METHODS: Phage
      surface display of cDNA libraries selectively enriched for allergen-expressing
      clones using IgE from allergic patients allows rapid isolation of large panels of
      allergens. For the characterization of all different clones present in enriched
      cDNA libraries in a fast and cost-effective way, high-throughput screening
      technology is required. RESULTS: The combination of selective enrichment of cDNA
      libraries based on biopanning against serum IgE from sensitized patients and
      automated robot technology for picking and high-density gridding of clones onto
      filter membranes, followed by hybridization, enables fast identification of all
      the different clones present in an enriched library. The consequent application
      of selective enrichment and robotic-based screening allows, within weeks, cloning
      and characterization of the whole allergenic repertoire of any organisms.
      CONCLUSIONS: Robotic-based high-throughput screening of clones selected for IgE
      binding capacity from phage surface-displayed cDNA libraries of Aspergillus
      fumigatus, Cladosporium herbarum, Coprinus comatus, Malassezia furfur, peanut and
      human lung tissue allowed rapid characterization of 81, 28, 37, 27, 8 and 151
      different sequences, respectively. All these cDNAs bear a high probability to
      encode allergens derived from the respective allergenic source.

PMID- 11306923
TI  - Rapid production of recombinant allergens in Nicotiana benthamiana and their
      impact on diagnosis and therapy.
AB  - BACKGROUND: Type I allergies are immunological disorders that afflict a quarter
      of the world's population. Recombinant allergens have improved the diagnosis of
      allergic diseases and allow the formulation of new therapeutic approaches. Over
      50% of all allergens are of plant origin. OBJECTIVE: We have applied a novel
      method of overexpressing plant allergens in the tobacco-related species Nicotiana
      benthamiana. METHOD: This method is based on the use of a chimeric tobacco mosaic
      virus that harbors a foreign gene sequence and directs its transcription after
      the infection of the host plant. RESULTS: We have expressed the model allergen
      Bet v 1, the major birch pollen allergen, and two Hevea brasiliensis latex
      allergens, the spina-bifida-associated allergens Hev b 1 and Hev b 3, in N.
      benthamiana using such a viral vector. Bet v 1, Hev b 1 and Hev b 3 produced by
      this method were recognized by patients' IgE suggesting that the plant-produced
      allergens were properly folded. Nonpurified Bet v 1 expressed in N. benthamiana
      leaves had the same immunogenicity as purified Bet v 1 expressed in Escherichia
      coli or natural Bet v 1 when tested in a murine model of type I allergy.
      CONCLUSION: We conclude that this plant expression system offers a viable
      alternative to fermentation-based production of allergens in bacteria or yeasts.

PMID- 11306924
TI  - Reduction in allergenicity of grass pollen by genetic engineering.
AB  - BACKGROUND: Hay fever and allergic asthma triggered by grass pollen allergens
      affect approximately 20% of the population in cool temperate climates. Ryegrass
      is the dominant source of allergens due to its prodigious airborne pollen
      production. Lol p 5 or group 5 is among the most important and widespread grass
      pollen allergen because it reacts with IgE antibodies of more than 90% of grass
      pollen-allergic patients, contains most of the grass pollen-specific IgE epitopes
      and elicits strong biological responses. Significant efforts have been made in
      developing diagnostic and therapeutic reagents for designing new and more
      effective immunotherapeutic strategies for treatment of allergic diseases. An
      alternative approach to this problem could be to reduce the amount of allergen
      content in the source plant. METHODS: High velocity microprojectile bombardment
      was used to genetically engineer ryegrass. Antisense construct targeted to one of
      major allergen, Lol p 5, was introduced. The expression of antisense RNA was
      regulated by a pollen-specific promoter. Pollen was analysed for IgE reactivity.
      RESULTS: Analysis of proteins with allergen-specific monoclonal and polyclonal
      antibodies did not detect Lol p 5 in the transgenic pollen. The transgenic pollen
      showed remarkably reduced allergenicity as reflected by low IgE binding capacity
      of pollen extract as compared to control pollen. The transgenic ryegrass plants
      in which Lol p 5 gene expression is perturbed showed normal fertile pollen
      development. CONCLUSIONS: Our studies showed that it is possible to selectively
      'switch off' allergen production in pollen of ryegrass demonstrating feasibility
      of genetic engineering of plants for reduced allergenicity.

PMID- 11306925
TI  - Identification of a novel cat allergen--cystatin.
AB  - BACKGROUND: Cat allergen is an important cause of sensitization among children
      with asthma in Japan. Although there is good evidence that cats produce other
      allergens, only one major allergen, Fel d 1, has been studied in detail. AIMS: To
      identify and define the molecular structure of the other potential cat allergens.
      METHODS: A cat skin cDNA library was screened using IgE antibodies to cat dander
      and selected clones were sequenced and expressed. RESULTS: One cDNA clone
      contained an open reading frame encoding a 98-amino acid residue protein.
      Sequence homology searches revealed a high degree of identity with bovine and
      human cystatin A, 79 and 75%, respectively. This cat cystatin clone contained the
      conserved cysteine protease motif and two of three lipocalin motifs. By plaque
      immunoassay, 60-90% of cat allergic sera had IgE Ab to cat cystatin. This
      cysteine protease inhibitor motif was partially conserved in dog allergens, Can f
      1 and Can f 2, which are lipocalins. Recombinant cystatin was produced in
      Escherichia coli cells and purified as an 11-kD protein, corresponding to the
      predicted MW of cystatin. The structure of cat cystatin was modeled on human
      cystatin B using the SWISS-MODEL. CONCLUSION: A newly identified allergen,
      cystatin, has been cloned from cat skin and is a member of the cysteine protease
      inhibitor family.

PMID- 11306926
TI  - Sensitisation to the lipid-binding apolipophorin allergen Der p 14 and the
      peptide Mag-1.
AB  - BACKGROUND: The IgE-binding peptides Mag 1 and Mag 3 and the high-molecular
      weight protein M-177 have been identified as parts of the apolipophorin-like
      group 14 house dust mite allergen. By analogy with the homologous insect
      proteins, apolipophorins are hydrophobic proteins found in lipid bodies and lipid
      transport particles. This explains why they degrade and are poorly represented in
      extracts. METHODS: We have examined the T cell stimulation induced by a 341
      residue recombinant Der p 14 peptide equivalent to the Mag 1 polypeptide examined
      by others. RESULTS: Peripheral blood mononuclear cells from both allergic and non
      allergic donors responded strongly in in vitro proliferation assays to the Der p
      14 peptide to induce markedly more (3)H-thymidine incorporation than Der p 2 and
      the release of Th2 cytokines. CONCLUSIONS: The apolipophorin-like group 14
      allergens, despite their predicted hydrophobicity and lipid-binding activity, can
      induce high IgE responses and T cell stimulation. They appear to be important
      mite allergens unsuited to representation by aqueous extracts of mites.

PMID- 11306927
TI  - Sequence polymorphisms and antibody binding to the group 2 dust mite allergens.
AB  - BACKGROUND: The group 2 allergens Der p 2, Der f 2 and Eur m 2 are 14-kD proteins
      with > 80% sequence identity. Isoforms within each genus have been identified
      which differ by 3-4 amino acids. The aim of this study was to investigate the
      importance of these substitutions to antibody binding. METHODS: Recombinant
      allergens were expressed and purified from Escherichia coli. ELISA and skin
      testing were used to evaluate antibody binding. Molecular modeling of the
      tertiary structure was preformed to examine the location of substitutions.
      RESULTS: The three Der f 2 isoforms and two of three of the Der p 2 isoforms
      reacted with all monoclonal antibodies (mAb). Der p 2.0101, the isoform with
      aspartate at position 114, bound all mAb except 1D8. Substitution of asparagine
      for aspartate restored binding of rDer p 2.0101 to mAb 1D8 and increased the
      correlation coefficient for IgE binding from 0.72 to 0.77. The three Der p 2
      isoforms showed comparable skin test reactivity to nDer p 2 and commercial
      extract. rEur m 2.0101 bound to all mAb except 7A1 and when compared with rDer p
      2 for IgE binding, r(2) = of 0.58 (n = 72). Lep d 2 did not react with mAb or
      with Dermatophagoides spp. allergic sera. Modeling revealed that Eur m 2, Lep d 2
      and Tyr p 2 retain the tertiary fold of Der p 2 and the substitutions are on the
      surface. CONCLUSIONS: mAb could distinguish isoform substitutions. IgE binding
      showed a good correlation among all isoforms, thus the recombinant allergens are
      useful for diagnosis.

PMID- 11306928
TI  - cDna cloning and characterization of a cross-reactive birch pollen allergen:
      identification as a pectin esterase.

PMID- 11306929
TI  - Lipid transfer protein: a pan-allergen in plant-derived foods that is highly
      resistant to pepsin digestion.
AB  - BACKGROUND: Lipid transfer proteins (LTPs) are stable and highly conserved
      proteins of around 10 kD. They have recently been identified as allergens in
      fruits of the Rosaceae family. OBJECTIVE: The aim of this study was to
      investigate whether the highly conserved structure of LTPs justifies a
      designation as a true pan-allergen, and to study the role of protein stability in
      allergenicity. METHODS: Thirty-eight patients with a positive skin prick test to
      Rosaceae fruit extracts were characterized by interviews and skin prick tests. To
      investigate IgE cross-reactivity between Rosaceae and non-Rosaceae LTPs, RAST and
      RAST inhibition as well as ELISA and ELISA inhibition were performed, using whole
      food extracts and purified natural and recombinant LTPs. To address the role of
      protein stability in the allergenicity of LTP, fruit extracts and LTPs were
      digested with pepsin. RESULTS: IgE antibodies to Rosaceae LTPs cross-reacted with
      a broad range of non-Rosaceae vegetable foods. Inhibition studies with purified
      natural and recombinant LTPs confirmed the role of LTP in this cross-reactivity.
      Many of the patients with this type of cross-reactive IgE antibodies had a
      clinical food allergy. In contrast to the typical birch Rosaceae cross-reactive
      patients, the oral allergy syndrome was frequently accompanied by more severe and
      systemic reactions. IgE reactivity to LTP was shown to be resistant to pepsin
      treatment of the allergen. CONCLUSION: LTP is a true pan-allergen with a degree
      of cross-reactivity comparable to profilin. Due to its extreme resistance to
      pepsin digestion, LTP is a potentially severe food allergen.

PMID- 11306930
TI  - Engineering, characterization and in vitro efficacy of the major peanut allergens
      for use in immunotherapy.
AB  - BACKGROUND: Numerous strategies have been proposed for the treatment of peanut
      allergies, but despite the steady advancement in our understanding of atopic
      immune responses and the increasing number of deaths each year from peanut
      anaphylaxis, there is still no safe, effective, specific therapy for the peanut
      sensitive individual. Immunotherapy would be safer and more effective if the
      allergens could be altered to reduce their ability to initiate an allergic
      reaction without altering their ability to desensitize the allergic patient.
      METHODS: The cDNA clones for three major peanut allergens, Ara h 1, Ara h 2, and
      Ara h 3, have been cloned and characterized. The IgE-binding epitopes of each of
      these allergens have been determined and amino acids critical to each epitope
      identified. Site-directed mutagenesis of the allergen cDNA clones, followed by
      recombinant production of the modified allergen, provided the reagents necessary
      to test our hypothesis that hypoallergenic proteins are effective
      immunotherapeutic reagents for treating peanut-sensitive patients. Modified
      peanut allergens were subjected to immunoblot analysis using peanut-positive
      patient sera IgE, T cell proliferation assays, and tested in a murine model of
      peanut anaphylaxis. RESULTS: In general, the modified allergens were poor
      competitors for binding of peanut-specific IgE when compared to their wild-type
      counterpart. The modified allergens demonstrated a greatly reduced IgE-binding
      capacity when individual patient serum IgE was compared to the binding capacity
      of the wild-type allergens. In addition, while there was considerable variability
      between patients, the modified allergens retained the ability to stimulate T cell
      proliferation. CONCLUSIONS: These modified allergen genes and proteins should
      provide a safe immunotherapeutic agent for the treatment of peanut allergy.

PMID- 11306943
TI  - The role of particulate matter in exacerbation of atopic asthma.
AB  - Increasing evidence shows that elevated levels of particulate matter (PM) can
      exacerbate existing asthma, while evidence that PM can promote the induction of
      asthma is limited. PM in ambient air has been associated with increased emergency
      room visits and medication use by asthmatics. Controlled human exposure studies
      of acid aerosols suggest increased responses among adolescent asthmatics.
      Increased ambient and indoor levels of bioaerosols (e.g., house dust mite, fungal
      spores, endotoxin) have been associated with exacerbation of asthma.
      Environmental Protection Agency (EPA) studies focus on the effects of exposing
      humans and animal models to a combination of various PM samples (e.g., diesel
      exhaust particles, oil fly ash) and allergens (e.g., house dust mite, ovalbumin).
      These research efforts to understand the mechanisms by which PM exposure can
      promote allergic sensitization and exacerbate existing asthma concentrate on the
      role of transition metals. Exposure of animal models to combined PM and allergen
      promotes allergic sensitization and increases allergic inflammation and airway
      hyperresponsiveness. Exposure of healthy human volunteers to emission source PM
      samples promotes inflammation and increased indices of oxidant formation
      correlating with the quantity of transition metals in the samples. Results of
      these studies suggest that transition metals in ambient PM promote the formation
      of reactive oxygen species and subsequent lung injury, inflammation, and airway
      hyperresponsiveness leading to airflow limitation and symptoms of asthma.

PMID- 11306944
TI  - Can Mycobacterium tuberculosis infection prevent asthma and other allergic
      disorders?
AB  - It is generally considered that tuberculosis (TB) is a disease which upregulates
      Th1 cell function. There is a hypothesis that infection of Mycobacterium
      tuberculosis may prevent allergic disorders such as bronchial asthma. However,
      our clinical experience of patients with TB somewhat conflicts this hypothesis.
      Hence, we investigated Th1/Th2 balance in the peripheral blood of patients with
      active TB by measuring serum levels of IgE antibody and by intracellular cytokine
      assay. We found that serum levels of IgE in the patients with active TB were
      significantly higher than in those with lung cancer or with COPD. In the TB
      patients, titers of IgE tended to correlate with disease severity. Intracellular
      cytokine assay demonstrated that IFN-gamma-positive cells were significantly
      decreased in the patients with active TB compared to normal controls. The ratio
      of IFN-gamma-positive (Th1-like)/IL-4-positive (Th2-like) cells was remarkably
      reduced in the TB patients (p < 0.0001). This ratio showed a significant negative
      correlation with erythrocyte sedimentation rate and with C-reactive protein.
      Therapy against TB for 2-3 months did not result in significant changes of the
      Th1/Th2 ratio. These findings suggest that infection of M. tuberculosis does not
      systematically upregulate Th1 cells in some patients, and is unlikely to prevent
      allergic disorders like asthma.

PMID- 11306945
TI  - Reduced interferon-gamma production and mutations of the interleukin-12 receptor
      beta(2) chain gene in atopic subjects.
AB  - BACKGROUND: The atopic patient has a predisposition to selective synthesis of IgE
      antibodies to common environmental antigens. IgE production is upregulated by
      interleukin-4 (IL-4) and downregulated by interferon-gamma (IFN-gamma). IL-12 is
      a cytokine that induces IFN-gamma production. The signal of IL-12 is transduced
      through the IL-12 receptor (IL-12R) and Stat4. METHODS: We examined IFN-gamma
      production in peripheral blood mononuclear cells (PBMCs) following stimulation
      with IL-12 or phytohemagglutinin (PHA) in healthy controls and atopic patients.
      Moreover, sequences of the IL-12R beta(2) chain gene were analyzed. RESULTS: The
      serum IgE levels were negatively correlated (p < 0.001) with IFN-gamma
      production. In 24 out of 75 atopic patients, IFN-gamma production in PBMCs
      following stimulation with IL-12 was under the detection limit, but PHA
      stimulation elicited detectable IFN-gamma production. Sequence analysis of the
      cDNA of IL-12R beta(2) revealed three kinds of distinct genetic mutations (2496
      del 91, 1577 A to G and 2799 A to G) in 10 unrelated subjects of the 24 whose IFN
      gamma production following IL-12 stimulation was under the detection limit. PBMCs
      cultured with IL-12 and PHA in these 10 subjects showed decreased tyrosine
      phosphorylation of Stat4. CONCLUSIONS: The results of our study indicate that
      atopic diseases are caused, in part, by impairment of the IL-12 signal cascade,
      which downregulates IgE production, and that the mutation of the IL-12R beta(2)
      chain gene is one of the causative genes for atopy.

PMID- 11306946
TI  - Secretion of proinflammatory eicosanoid-like substances precedes allergen release
      from pollen grains in the initiation of allergic sensitization.
AB  - It is commonly believed that allergic sensitization starts when an allergen
      contacts the surface of an antigen-presenting cell in mucosal or skin epithelia.
      Most studies dealing with this aspect use allergen extracts as stimulus. Under
      natural exposure conditions, however, the bioavailability of allergen depends on
      allergen liberation from internal binding sites within the allergen carrier, e.g.
      pollen grains. In comparing total protein and major allergen release from timothy
      grass (Phleum pratense L.) pollen freshly collected on rural meadows or near high
      traffic roads, there was a striking difference between the pollen, with higher
      allergen release rates from rural meadow pollen grains. Thus, allergen release
      does not explain the higher prevalence rates of atopic sensitization and disease
      observed in many epidemiological studies in children exposed to automobile
      exhaust. Therefore, other possible effectors from pollen grains were
      investigated. Pollen grains incubated in protein- free buffer were found to
      secrete significant amounts of eicosanoid-like substances, namely leukotriene
      (LT) B(4)-like and prostaglandin E(2)-like substances, in a pH-, time- and
      temperature-dependent fashion. The highest values of eicosanoid secretion were
      found in birch, grass and mugwort pollen, while pine (Pinus sylvestris L.) pollen
      showed only marginal eicosanoid-like secretion. Additionally, the release of
      these substances was significantly higher from pollen which had been collected
      near roads with heavy traffic, indicating a stronger proinflammatory activity of
      these pollen grains. In order to investigate the effects of air pollutants,
      native pollen grains were exposed in a dose- and time-dependent fashion in a
      fluidized bed reactor to traffic-related pollutants, e.g. volatile organic
      compounds (toluene, m-xylene), leading again to a significant increase in the
      secretion of LTB(4)-like immunoreactivity, in contrast to exposure with sulfur
      dioxide. This finding opens a new dimension of understanding of the early events
      in allergic sensitization, indicating that proinflammatory effects of the
      allergen carrier, e.g. the pollen grain itself, can lead to activation of the
      mucosal membrane. These findings might help to also explain the higher prevalence
      rates of pollen allergy in areas with high automobile exhaust emissions.
      Furthermore, the allergenic 'potency' of various allergens has to be redefined at
      the allergen carrier level with regard to different stages of allergen and
      mediator release prior to the contact with the host's immune system.

PMID- 11306947
TI  - Serum IgG and IgG4 antibodies to Fel d 1 among children exposed to 20 microg Fel
      d 1 at home: relevance of a nonallergic modified Th2 response.
AB  - Exposure to foreign antigens is an essential element of all immune responses,
      including allergic sensitization. For some allergens (e.g. mite and cockroach),
      the prevalence of sensitization is directly correlated with exposure. However,
      for allergens derived from domestic animals, several studies have suggested that
      children with a cat in the home have a decreased risk of sensitization and
      asthma. We have now shown that many children exposed to greater than 20 microg of
      Fel d 1/g of dust at home made an IgG and IgG4 antibody response to Fel d 1
      without IgE antibody. This modified Th2 response is not associated with symptoms
      and should be regarded as a form of immunological tolerance. The fact that the
      dose-response relationship between cat exposure and sensitization is bell shaped,
      while that for mite exposure and sensitization is linear, is highly relevant to
      understanding the role of allergens in the increase in allergic disease.

PMID- 11306948
TI  - Studies of different aspects of the role of protein kinase C in mast cells.
AB  - Mast cells induce the inflammatory process when their FcepsilonRI receptors
      aggregate in response to an antigen binding to immunoglobulin E. Direct
      interactions between FcepsilonRI receptor cytoplasmic domains and various
      intracellular proteins initiate diverse signal transduction pathways resulting in
      the immediate release of proinflammatory agents. A delayed response also occurs
      that includes the release of various cytokines. It is clear that the activation
      of kinases, such as protein kinase C (PKC), is a requirement for both the early
      and delayed responses of this inflammatory process. In this review we present the
      results of various studies investigating the role of PKC isozymes in mast cells.

PMID- 11306949
TI  - Nonspecific B and T cell-stimulatory activity mediated by mast cells is
      associated with exosomes.
AB  - Bone marrow-derived mouse mast cells (BMMC) and mast cell lines P815 and MC9 have
      recently been shown to induce antigen-independent B and T lymphocyte activation.
      It has been demonstrated that a physical contact between mast cells and B and T
      lymphocytes is not necessary since mast cell supernatants contain full activity.
      Electron microscopy studies revealed the presence in mast cell supernatants of
      small vesicles called exosomes with a heterogeneous size from 60 to 100 nm of
      diameter. When cocultured with spleen cells, purified exosomes induce B and T
      cell blast formation, proliferation as well as IL-2 and IFN-gamma production. In
      contrast to P815 and MC9 mast cell lines, a pretreatment with IL-4 is required
      for BMMC to produce active exosomes. Structurally, these exosomes were found to
      harbor immunologically relevant molecules such as MHC class II, CD86, LFA-1 and
      ICAM-1. Here we provide for the first time the evidence that mast cells use
      exosomes as sophisticated messengers to communicate with cells of the immune
      system.

PMID- 11306950
TI  - A perspective: regulation of IgE receptor-mediated mast cell responses by a LAT
      organized plasma membrane-localized signaling complex.
AB  - BACKGROUND: To understand how the high-affinity IgE receptor (FcepsilonRI)
      communicates with downstream effectors, we focused on exploring the functional
      importance of the FcepsilonRI-mediated formation and localization of a signaling
      complex that contains the hematopoietic cell-specific scaffolding protein linker
      for activation of T cells (LAT) and the guanine nucleotide exchange factor Vav1.
      METHODS: Using the mast cell line RBL-2H3, we explored the localization of these
      proteins by confocal microscopy and cell fractionation. Additionally, the
      mechanism of function and the importance of LAT and Vav1 to mast cells was
      studied in genetically disrupted mice and in mast cells derived from their bone
      marrow. RESULTS: We found that LAT, Vav1 and the adapter molecule SLP-76
      associated in detergent-resistant microdomains (lipid rafts) found in the plasma
      membrane upon FcepsilonRI stimulation. In the absence of LAT, mast cells showed a
      remarkable loss of the secretory response and reduced cytokine responses. Vav1
      deficiency also affected secretion, although not to the extent of LAT deficiency,
      and inhibited IL-2 and IFN-gamma production. LAT- and Vav1-deficient mice showed
      reduced blood histamine levels after a systemic anaphylaxis challenge as compared
      to their normal counterparts. CONCLUSIONS: The results demonstrate that LAT is a
      central mediator in IgE receptor signaling by regulating multiple signaling
      pathways that affect mast cell degranulation and cytokine production. Vav1, a
      component of this LAT-containing signaling complex, regulates a specific subset
      of these responses.

PMID- 11306951
TI  - SDF-1 induces IL-8 production and transendothelial migration of human cord blood
      derived mast cells.
AB  - BACKGROUND: Mast cell numbers and expression of chemokines are known to increase
      in the context of angiogenesis and inflammation, but the mechanisms by which this
      occurs are not understood. Stromal-derived factor-1 (SDF-1) is an important
      chemokine in angiogenesis and cell migration. The effects of SDF-1 on human mast
      cells were examined. METHODS: Expression of the SDF-1 receptor CXC chemokine
      receptor 4 (CXCR4) on mast cells was examined by RT-PCR and flow cytometry. The
      ability of labeled cord blood-derived mast cells to migrate across HUVEC
      monolayers in response to SDF-1 was determined. The cytokine and chemokine
      responses of cord blood-derived mast cells to SDF-1 treatment over 24 h were
      examined by ELISA. RESULTS: Cord blood-derived human mast cells expressed the
      CXCR4 receptor for SDF-1 and migrated across HUVEC monolayers in response to this
      chemokine. Treatment of cord blood-derived mast cells with SDF-1 did not induce
      degranulation or the production of several cytokines but did induce a highly
      selective IL-8 response. CONCLUSION: Human mast cells can both migrate across
      vascular endothelium and produce the pro-angiogenic chemokine IL-8 in response to
      SDF-1. These responses may be important in angiogenic processes.

PMID- 11306952
TI  - Expression of the chemokine receptor CCR3 on human mast cells.
AB  - BACKGROUND: The aim of this study was to investigate whether human mast cells
      express functional active CCR3 receptors, which are activated by CC chemokines.
      These ligands include the CCR3-selective chemokines eotaxin and eotaxin-2 and the
      more promiscuous CC chemokines, MCP-4, MCP-3, MCP-2 and RANTES. METHODS:
      Immunohistochemical analysis was performed on skin, gut and lung specimens.
      Double immunostaining was performed with anti-CCR3 and antitryptase, and anti
      CCR3 and antichymase antibody (Ab) by using the avidin-biotin-peroxidase system
      with two different substrates. Mast cells were isolated and purified from human
      lung parenchyma (HLMC) by countercurrent elutriation followed by discontinuous
      Percoll density gradient. Flow-cytometric analysis of HLMC surface CCR3
      expression was performed with the monoclonal Ab anti-CCR3 (7B11). Functional
      activation of HLMC was verified by the ability of cells to release histamine
      and/or migrate in response to eotaxin. RESULTS: High percentages (>70%) of
      tryptase-positive cells showing CCR3 expression were found in the skin and in the
      intestinal submucosa, whereas much lower percentages (< or = 20%) were found in
      the intestinal mucosa and in the lung interstitium. Eotaxin (1-100 nM) neither
      induced histamine release from HLMC nor enhanced anti-IgE-induced histamine
      release. In contrast, eotaxin (10-100 nM) and RANTES (10-100 nM) induced HLMC
      chemotaxis in vitro. Preincubation of HLMC with antibody anti-CCR3 (5 microg/ml)
      before loading into the chemotaxis chamber abrogated chemotaxis elicited by
      eotaxin. Double immunostaining with anti-CCR3 and anti-chymase antibody showed
      that the vast majority of CCR3-expressing mast cells in the various human tissues
      examined were tryptase-chymase double-positive. CONCLUSIONS: These results
      indicate that CCR3 is expressed on human mast cells and that these cells are
      attracted by CCR3-binding chemokines.

PMID- 11306953
TI  - Interleukin-4 induces a switch of human intestinal mast cells from
      proinflammatory cells to Th2-type cells.
AB  - BACKGROUND: During the last years, mast cells have been recognized as a potent
      cellular source of multiple cytokines. However, little is known about the
      regulation of cytokine production by mature human mast cells derived from mucosal
      sites. METHODS: Human mast cells were isolated from intestinal mucosa and
      cultured for 14 days in the presence of stem cell factor (SCF) alone or in
      combination with IL-4. Mast cells were then stimulated by IgE receptor cross
      linking or bacterial infection and cytokine production was examined by RT-PCR and
      ELISA. RESULTS: We found that human intestinal mast cells produce proinflammatory
      cytokines such as TNF-alpha, IL-1beta and IL-6 without further stimulation.
      Stimulation of the cells with gram-negative bacteria (Escherichia coli and
      others) caused an upregulation of TNF-alpha expression. Following IgE receptor
      cross-linking, we found additional expression of the Th2 cytokines IL-3, IL-5 and
      IL-13. Interestingly, mRNA for IL-3, IL-5 and IL-13 was also expressed in
      unstimulated mast cells provided they were cultured in the presence of SCF and IL
      4. Moreover, IL-4 rendered mast cells capable of releasing IL-5 in response to
      bacterial challenge. CONCLUSION: In the presence of the mast cell survival factor
      SCF, mature human mast cells produce predominantly proinflammatory cytokines,
      whereas in the presence of SCF and IL-4, mast cells produce not only
      proinflammatory but also Th2 cytokines.

PMID- 11306954
TI  - Further characterization of FcgammaRII and FcgammaRIII expression by cultured
      human mast cells.
AB  - BACKGROUND: We have reported that resting human mast cells exhibit minimal
      expression for FcgammaRI, and that interferon-gamma will upregulate this
      expression. The expression of FcgammaRII and FcgammaRIII by human mast cells
      remains to be fully examined. METHODS: To investigate FcgammaRII and FcgammaRIII
      expression, we determined mRNA and protein expression of FcgammaRII and
      FcgammaRIII in human peripheral blood CD34+ derived cultured mast cells by RT-PCR
      and flow cytometry. The expression of FcgammaRII and FcgammaRIII in intact and
      permeabilized mast cells was also compared. We measured histamine release to
      monitor mast cell degranulation following cross-linking of FcgammaRII. RESULTS:
      We found by RT-PCR that resting human mast cells exhibit mRNA for FcgammaRIIA,
      FcgammaRIIb1, FcgammaRIIb2 and FcgammaRIII but not FcgammaRIIC. FACS analysis of
      Fcgamma receptors in intact versus permeabilized mast cells showed expression of
      FcgammaRII to be 42.2 +/- 3.9% and this was unchanged by permeabilization.
      FcgammaRIII protein expression was minimal and this was also unchanged by
      permeabilization. Aggregation of FcgammaRII on human mast cells led to no
      significant degranulation as evidenced by histamine release. CONCLUSIONS: In
      addition to FcgammaRI expression, human mast cells express FcgammaRIIA,
      FcgammaRIIb1, FcgammaRIIb2 and FcgammaRIII mRNA, and significant surface
      expression of FcgammaRII. Aggregation of FcgammaRII on cultured human mast cells
      in this model was not followed by histamine release.

PMID- 11306960
TI  - Selective regulation of T cell IL-5 synthesis by OM-01, JTE-711 and p38 MAP
      kinase inhibitor: independent control of Th2 cytokines, IL-4 and IL-5.
AB  - BACKGROUND: Helper T cells are involved in chronic eosinophilic inflammation.
      Control of cytokine production seems to be an effective management. METHODS: The
      effect of nonactin, SB203580, a p38 MAP kinase inhibitor, and JTE-711 on the
      cytokine production of allergen-specific T cell clones was determined. The effect
      of nonactin on the airway eosinophilia was investigated using murine asthma
      model. RESULTS: Nonactin suppressed IL-5 synthesis by human Th cells in a dose
      dependent manner without affecting IL-2 or IL-4 synthesis, and still
      significantly suppressed murine airway eosinophilia induced by the antigen
      inhalation. SB203580 and JTE-711 also selectively inhibited IL-5 synthesis in
      vitro. CONCLUSION: Synthesis of IL-5 by human Th cells can be differentially
      regulated from that of other major T cell cytokines. The in vivo effects of
      selective IL-5 synthesis inhibitors suggest that IL-5 is the reasonable target
      for the regulation of allergic disorders accompanied by eosinophilic
      inflammation.

PMID- 11306961
TI  - Regulation of cytokine production in T-cell responses to inhalant allergen:GATA-3
      expression distinguishes between Th1- and Th2-polarized immunity.
AB  - BACKGROUND: The precise nature of allergen-specific cytokine responses in atopics
      versus non-atopics, in particular the 'Th1 polarity' of responses in non-atopics,
      remains controversial. This is due in part to the relative insensitivity of
      cytokine detection systems, and associated variations in kinetics of cytokine
      production and catabolism in in vitro culture systems. As an alternative to
      cytokine measurement, this study focuses on expression of the transcription
      factor GATA-3 for analysis of allergen-specific Th cell responses. METHODS: Cord
      blood mononuclear cells were Th1- or Th2-polarized by culture in IL-12- or IL-4
      employing established methods; PBMC from house dust mite (HDM)-sensitive atopics
      and controls were stimulated overnight with HDM; cytokine production was measured
      by ELISA and GATA-3 mRNA expression by PCR. RESULTS: Cytokine-driven Th2
      polarization of naive T cells is associated with marked upregulation of GATA-3
      expression, whereas a reciprocal expression pattern accompanies differentiation
      towards the Th1 cytokine phenotype. In T cells from HDM skin prick test-positive
      (HDM-SPT+/HDM-IgE+) volunteers, overnight stimulation results in marked
      upregulation of GATA-3 expression, compared to an equally marked downregulation
      of expression in T cells from SPT-/IgE- subjects. In subjects who are HDM-SPT+
      but IgE-, GATA-3 expression levels remained relatively stable during culture with
      HDM. CONCLUSIONS: Upregulation of GATA-3 expression in PBMC is a hallmark of the
      early phase of Th2 recall responses to specific allergen in atopics. The
      reciprocal expression pattern observed in HDM-specific recall responses of non
      atopics provides independent confirmation of the presence of underlying Th1-like
      immunity in these subjects. The parallel findings in neonatal T cells suggest
      that the same approach may be utilized for monitoring the progress of allergen
      specific Th1/Th2 memory development during early childhood, and hence in
      assessment of risk for future allergic disease.

PMID- 11306962
TI  - Mechanism of IL-10-induced T cell inactivation in allergic inflammation and
      normal response to allergens.
AB  - BACKGROUND: Induction of specific unresponsiveness (tolerance/anergy) in
      peripheral T cells and recovery by cytokines from the tissue microenvironment
      represent two key steps in specific immunotherapy (SIT) with whole allergen or
      antigenic T cell peptides. METHODS: Antigen-specific T cell responses and
      molecular mechanisms of T cell inactivation were investigated during conventional
      SIT, T cell epitope peptide immunotherapy and natural exposure to bee venom in
      allergic and hyperimmune individuals. RESULTS: T cell unresponsiveness, initiated
      by autocrine action of IL-10, is characterized by suppressed proliferative and
      cytokine responses. The unresponsive T cells can be reactivated by different
      cytokines that may mimic the microenvironmental cytokine influence. IL-10
      initiates peripheral tolerance by blocking the CD28 costimulatory signal in T
      cells. Coprecipitation experiments reveal that upon stimulation CD28 and IL-10
      receptor are physically associated in T cells. Accordingly, IL-10 binding to its
      receptor inhibits CD28 tyrosine phosphorylation, the initial step of the CD28
      signaling pathway. This leads to inhibition of phosphatidylinositol 3-kinase p85
      binding to CD28. IL-10 only affects T cells that receive a stimulation with low
      numbers of triggered T cell receptors and that require costimulatory signals by
      CD28. CONCLUSION: These data demonstrate the pivotal role of autocrine IL-10 and
      the interaction of its receptor with CD28 in the induction of T cell tolerance as
      an immunoregulatory mechanism controlling antigen-specific T cell responses.

PMID- 11306964
TI  - T cytotoxic 1 and T cytotoxic 2 CD8 T cells both inhibit IgE responses.
AB  - BACKGROUND: It is well recognized that CD8 T cells inhibit IgE responses. In this
      study, we investigated the mechanism of CD8 T cell-mediated IgE suppression by
      comparing the capacity of T cytotoxic 1 (Tc1) and T cytotoxic 2 (Tc2) CD8 T cells
      to inhibit IgE responses to ovalbumin (OVA). METHODS: Tc1 and Tc2 CD8 T cells
      were generated from OVA(257-264)-specific Vbeta5.2 T cell receptor (TcR)
      transgenic mice by stimulation with anti-CD3 and anti-CD28 under Tc1 and Tc2
      polarizing conditions. Tc1 and Tc2 Vbeta5.2 TcR CD8 T cells (10(6)) were
      adoptively transferred to syngeneic mice, and following immunization with 100
      micro of OVA/alum, serum IgE antibodies were measured by passive cutaneous
      anaphylaxis and expressed as the highest dilution that gave a detectable skin
      response. RESULTS: Both Tc1 and Tc2 CD8 T cells from OT-I mice inhibited IgE.
      CONCLUSION: Both Tc1 and Tc2 CD8 T cells promote Th1 immunity and inhibit IgE
      responses. This process appears to be independent of CD8 T cell-derived IFN
      gamma, as both Tc2 (IFN-gamma-) and Tc1 (IFN-gamma+) CD8 T cells inhibited IgE.

PMID- 11306963
TI  - Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular
      use of albuterol in asthma.
AB  - BACKGROUND: Regular use of inhaled beta-adrenergic agonists may have adverse
      effects in some asthma patients. Polymorphisms of the beta(2)-adrenergic receptor
      (beta(2)-AR) can affect its regulation; however, results of smaller studies of
      the effects of such polymorphisms on response to beta-agonist therapy have been
      inconsistent. METHODS: We examined the possible effects of polymorphisms at
      codons 16 (beta(2)-AR-16) and 27 (beta(2)-AR-27) on response to albuterol by
      genotyping 190 asthmatics who had participated in a trial of regular versus as
      needed albuterol use. RESULTS: During the 16-week treatment period, patients
      homozygous for arginine (Arg/Arg) at beta(2)-AR-16 who used albuterol regularly
      had a small decline in morning peak expiratory flow (AM PEF). This effect was
      magnified during a 4-week run-out period, when all patients returned to as-needed
      albuterol only. By the end of the study, Arg/Arg subjects who had used albuterol
      regularly had an AM PEF 30.5 +/- 12.1 liters/min lower (p = 0.012) than Arg/Arg
      patients who had used albuterol as needed only. Subjects homozygous for glycine
      at beta(2)-AR-16 showed no such decline. Evening PEF also declined in the Arg/Arg
      regular but not in as-need albuterol users. No significant differences between
      regular and as-needed treatment were associated with polymorphisms at beta(2)-AR
      27. CONCLUSIONS: Polymorphisms of the beta(2)-AR may influence airway responses
      to regular inhaled beta-agonist treatment.

PMID- 11306965
TI  - Histamine upregulates Th1 and downregulates Th2 responses due to different
      patterns of surface histamine 1 and 2 receptor expression.
AB  - Histamine, which acts via G protein-coupled receptors, is an important mediator
      of immediate hypersensitivity and is also able to influence the nature of T cell
      responses. We demonstrated that TH1 and Th2 cells express distinct surface
      histamine receptor patterns and that Th1-type responses are enhanced by
      histamine, whereas Th2-type responses are negatively regulated, due to different
      intracellular signals generated by histamine stimulation. These findings account
      for negative feedback regulation in a wide variety of pathologies.

PMID- 11306966
TI  - Allergic sensitization and allergen exposure during pregnancy favor the
      development of atopy in the neonate.
AB  - BACKGROUND: Several studies have considered that the in utero environment plays
      an important role in the onset of the allergic phenotype. We assessed whether
      allergic sensitization and allergen exposure during pregnancy favor the postnatal
      onset of allergy in the neonate. METHODS: BALB/c mice were sensitized to
      ovalbumin (OVA) before mating followed by allergen aerosol exposure during
      pregnancy. T and B cell responses in offspring were followed up until day 60
      postpartum. At the age of 4 weeks offspring were exposed to a heterologous
      antigen, beta-lactoglobulin (BLG). RESULTS: Pregnant mice developed immediate
      hypersensitivity responses and Th-2/ Th-0 immunity following allergen aerosol
      exposure. At birth, T cells from offspring of nonsensitized BALB/c mice were
      characterized by an impaired IFN-gamma production, which was lowered even further
      in offspring of OVA-sensitized BALB/c mice. Offspring of OVA-sensitized BALB/c
      mice responded with immediate-type cutaneous hypersensitivity reactions to OVA
      which could be related to the pre- and postnatal transfer of maternal OVA
      specific IgG1 antibodies. After exposure to BLG, offspring of OVA-sensitized
      BALB/c mice developed an accelerated Th-2-driven immune response compared to
      offspring from nonsensitized BALB/c mice as indicated by enhanced anti-BLG IgG1
      antibody production and increased numbers of positive immediate-type cutaneous
      hypersensitivity reactions to BLG. CONCLUSION: Our data suggest that Th-2/Th-0
      immunity present during pregnancy has a decisive impact on shaping the Th-1/Th-2
      T cell profile in response to postnatal allergen exposure.

PMID- 11306967
TI  - Genetics of allergic disease: evidence for organ-specific susceptibility genes.
AB  - BACKGROUND: While previous studies have probed the genetics of asthma and serum
      IgE levels, there have been no studies on the genetics of allergic
      conjunctivitis. This paper describes the initial phase of a genetic study of
      allergic conjunctivitis. METHODS: Approximately 117 families with probands with
      allergic conjunctivitis were recruited generating 245 affected sib pairs. Each
      family member completed a detailed questionnaire on atopic symptoms, and results
      from skin testing were obtained. Genomic DNA was extracted and genotyped using
      thirty-five polymorphic markers spanning human chromosomes 5, 6, 11, 12, 16 and
      17. Heritability was assessed using the POINTER program, and nonparametric
      linkage analysis using the BETA program. RESULTS: Evidence for genetic linkage of
      allergic conjunctivitis was obtained for chromosomes 5, 16 and 17. Weak linkage
      was detected for chromosome 6 when studies were restricted to specific allergens.
      No evidence for linkage was detected for chromosomes 11 and 12. CONCLUSIONS:
      Consistent with heritability analysis discussed in this paper, genetic linkage
      for allergic conjunctivitis is shown to differ from that reported for atopic
      asthma. This indicates that there are likely to be organ-specific disease
      susceptibility genes, which together with general atopy genes target the allergic
      response to specific mucosal tissues.

PMID- 11306968
TI  - Inhibition of allergic inflammation by C-terminal peptides of the prohormone
      submandibular rat 1 (SMR-1).
AB  - BACKGROUND: The C-terminal of the prohormone submandibular rat 1 protein (SMR-1)
      contains several small peptides that reduce the severity of allergic inflammation
      and septic shock, and are part of the cervical sympathetic trunk-submandibular
      gland (SMG) axis of neuroendocrine immunology. These peptides include the
      heptapeptide, submandibular gland peptide-T and the tripeptide FEG. The D
      isomeric form of this tripeptide, feG, which is active when administered orally,
      reduces LPS-provoked leukocyte rolling on mesenteric venules and influx of
      inflammatory cells into the peritoneum and intestinal muscle. METHODS: To
      investigate the mechanism of action of these peptides, the influx of inflammatory
      molecules into the airways, and several properties of human neutrophils were
      examined. RESULTS: Oral feG (1 mg/kg) inhibited the influx of inflammatory cells
      into the airways lumen of allergen challenged, sensitized Brown Norway rats. This
      inhibition occurred whether feG was given 30 min prior to 6 h post allergen
      challenge. Moreover, feG in picomolar to nanomolar concentrations inhibited PAF
      elicited chemotaxis by 30-40%, but the peptides did not affect superoxide
      production or phagocytosis by neutrophils. feG reduced PAF-stimulated expression
      of CD11b. CONCLUSIONS: feG may exert its anti-inflammatory effects by modulating
      the expression and functions of beta(2) integrins. The CST-SMG axis may be a
      major neuroendocrine pathway that modulates allergic asthma and other
      inflammatory responses.

PMID- 11306969
TI  - Nerve growth factor induces airway hyperresponsiveness in mice.
AB  - BACKGROUND: Previous studies indicated an upregulation of nerve growth factor
      (NGF) production during allergic inflammation. However, the function of NGF in
      the lungs is currently poorly understood. It was suggested that NGF could play an
      important role in the pathophysiology of airway hyperresponsiveness. The
      regulatory network between immunological events and altered neuronal control of
      airway smooth muscle contractility remains to be defined. METHODS: NGF was
      delivered into the airways of mice either by nasal instillation or by genetic
      engineering. Airway reactivity was then measured by electrical field stimulation.
      RESULTS: Treatment of mice with NGF induced airway hyperresponsiveness to a
      similar extent as demonstrated in allergen-sensitized mice. NGF-transgenic mice,
      overexpressing NGF in Clara cells, were hyperreactive in comparison to wild-type
      mice. CONCLUSION: These data suggest that NGF by itself determines the induction
      of airway hyperresponsiveness in the absence of airway inflammation in mice.

PMID- 11306970
TI  - Immune reactivity to mite allergens in nonatopic subjects: immune deviation or
      immune ignorance.
AB  - Most subjects without IgE to Dermatophagoides pteronyssinus do not have IgG to
      Der p 1 or Der p 2 (as measured by RIA). However, by immunoblot or ELISA, IgG
      reactivity (mostly IgG1) to mite components is easily detectable. This
      discrepancy is caused largely by immune reactivity to mite components with a high
      molecular weight under native conditions (possibly mite gut flora cross-reactive
      with human gut flora) and partially by the presence of IgG with low affinity for
      fluid-phase antigen. We conclude that the pattern of IgG antibody in subjects
      without IgE to mites does not support the notion of immune deviation, but rather
      indicates a lack of a mite-induced high-affinity immune response.

PMID- 11306976
TI  - Invited lecture: role of membrane receptors in the release of T helper 1 and 2
      cytokines by eosinophils.

PMID- 11306977
TI  - Aminooxypentane-RANTES induces CCR3 activation and internalization of CCR3 from
      the surface of human eosinophils.
AB  - Eosinophils are predominant effector cells in allergic diseases attracted by
      several CC chemokines into the inflammatory tissue. According to their important
      role in attracting leukocytes, several kinds of chemokine receptor antagonists
      have been developed. Therefore, the aim of this study was to investigate the
      effect of aminooxypentane (AOP)-RANTES on the activation of the CC chemokine
      receptor 3, CCR3, exemplary on human eosinophils, because they represent the
      dominant CCR3+ cell type. AOP-RANTES dose-dependently induced an increase of
      intracellular calcium concentration ([Ca(2+)](i)) and a release of reactive
      oxygen species, which could be inhibited by pertussis toxin, in human eosinophils
      from normal nonatopic donors. AOP-RANTES was as effective as RANTES but less
      effective than eotaxin and eotaxin-2 in the activation of the respiratory burst.
      Flow-cytometric analyses revealed that eosinophils constitutively expressed the
      CC chemokine receptors CCR1 and CCR3, whereas CCR5 was not expressed. AOP-RANTES,
      RANTES, eotaxin and eotaxin-2, but not Met-RANTES, induced a downregulation of
      CCR3 at 37 degrees C. Reexpression of CCR3 on eosinophils was observed within 120
      min. Whereas no differences of CCR3 downregulation and recycling after
      stimulation with AOP-RANTES, RANTES, eotaxin and eotaxin-2 were found there
      exists a distinct profile of activity with respect to the activation of the
      respiratory burst in human eosinophils.

PMID- 11306978
TI  - Role of apoptosis in atopic dermatitis.

PMID- 11306979
TI  - Effects of retinoids on in vitro and in vivo IgE production.
AB  - BACKGROUND: Retinoids modulate the growth and number of different cell types,
      including B cells. We could previously show that retinoic acid (RA) strongly
      inhibits CD40 + IL-4-mediated IgE production in vitro. The aim of the present
      study was to extend these findings regarding the potential use of retinoids for
      the treatment of allergic diseases. METHODS: In vitro IgE production was studied
      in anti-CD40 + IL-4-stimulated peripheral blood mononuclear cells (PBMC) from
      allergic donors in the presence of 10(-15)-10(-5) M all-trans and 13-cis RA and
      in ovalbumin (OVA)-sensitized BALB/c mice treated with RA (20 mg/kg) before and
      during sensitization. IgE and IgG1 levels were determined in the sera of the mice
      at day 21 after 2 injections (days 1 and 8) of aluminum hydroxide-absorbed OVA.
      RESULTS: All-trans and 13-cis RA inhibited in vitro IgE production from PBMC in a
      dose-dependent manner, but were more efficient in atopic dermatitis patients with
      low total serum IgE levels (< 400 kU/ml), maximal inhibition for all-trans RA at
      10(-7) M (87%) and for 13-cis RA at 10(-5) M (96%) compared to patients with high
      serum IgE levels (>2,000 kU/ml), maximal inhibition for both all-trans and 13-cis
      RA at 10(-5) M (53 and 39%, respectively). In contrast, the in vivo data from OVA
      sensitized mice revealed comparable total IgE and IgG1 levels in control versus
      all-trans RA or CD336-treated groups, specific IgE was even higher in the CD336
      treated group (n = 10, 2,814 ng/ml), and was comparable in mice treated with OVA
      alone or with additional all-trans RA (n = 10, 1,447 and 1,354 ng/ml,
      respectively). CONCLUSIONS: These results indicate that the efficacy of retinoids
      to inhibit IgE production in vitro depends on the frequency of switched cells in
      the peripheral blood and that in an in vivo model using OVA-sensitized mice,
      retinoids fail to inhibit IgE production.

PMID- 11306980
TI  - The role of STAT1 in activation of IL-3- and IL-5-induced eosinophils by
      interferon gamma.
AB  - Tyrosine phosphorylation of STAT1alpha in eosinophils after IFN-gamma stimulation
      has been shown, but the biological significance of eosinophil STAT1alpha
      activation in transmitting the signals through the IFN-gamma receptor remains
      unknown. The purpose of this study is to determine whether STAT1 is involved in
      the regulation of eosinophils by IFN-gamma-IFN-gamma receptor interaction. rhIL-3
      and rhIL-5-induced eosinophils from CD34+ cells of cord blood on day 28 of
      culture were used. The cells were washed and further incubated in IL-3- and IL-5
      free medium for 48 h. The induced eosinophils constitutively expressed CD69 and
      lost this expression after a further 48-hour incubation without the cytokines.
      IFN-gamma significantly upregulated CD69 expression on the 48-hour incubated
      cells. In inhibitory experiments on STAT1, a phosphorothioate oligo antisense DNA
      against STAT1alpha was added to IL-3- and IL-5-containing medium from day 15 to
      day 28 of culture. The oligo DNAs altered neither the expressions of myeloid cell
      marker CD9 and 13 nor the expression of IFN-gamma receptor on the cells. The
      added STAT1alpha antisense, but not sense, DNA significantly reduced STAT1alpha
      mRNA expression in the cells. The STAT1 antisense also significantly inhibited
      IFN-gamma-induced CD69 expression on the 48-hour incubated eosinophils. In
      conclusion, these results indicate that IFN-gamma induces CD69 expression in the
      induced eosinophils through STAT1alpha, suggesting that STAT1alpha may play a
      significant role in eosinophil regulation by IFN-gamma.

PMID- 11306981
TI  - Clinical and immunological features of patients with interleukin-5-producing T
      cell clones and eosinophilia.
AB  - Recent work suggests that in some patients with the hypereosinophilic syndrome, a
      clone of abnormal T cells produces large amounts of interleukin-5. In this study,
      we examined 60 patients with idiopathic eosinophilia. Sixteen patients had
      circulating T cells with an aberrant immunophenotype that, in most cases, were
      associated with different forms of skin inflammation. The abnormal T cells
      produced large amounts of interleukin-5, which may have increased eosinophil
      differentiation in the bone marrow of these patients.

PMID- 11306982
TI  - Regulation of IL-5 receptor on eosinophil progenitors in allergic inflammation:
      role of retinoic acid.
AB  - We and others have shown that IL-5 plays a central role in eosinophil and
      basophil differentiation, exerting its effects through the IL-5 receptor (IL-5R).
      Little is currently known concerning regulation of IL-5Ralpha gene transcription
      in the context of commitment of hemopoietic progenitor cells to the eosinophil
      and basophil lineages; recent studies have indicated that IL-5 itself can
      regulate IL-5Ralpha expression on mature eosinophils. We now provide evidence to
      indicate that IL-5 can upregulate IL-5Ralpha on bone marrow CD34+ progenitors in
      vitro, as we have demonstrated in vivo in atopic asthmatics. Given that all-trans
      retinoic acid (ATRA) is known to modulate some granulopoiesis, causing
      neutrophilic differentiation, we examined the effects of ATRA on
      eosinophil/basophil differentiation and IL-5Ralpha expression. In cultures of
      normal human bone marrow, ATRA selectively suppressed eosinophil/basophil
      differentiation. Similarly, ATRA inhibited eosinophil/basophil differentiation of
      cord blood CD34+ cells, while neutrophil differentiation proceeded without
      impediment. Most importantly, these effects of ATRA on CD34+ cells were
      associated with selective, dose-dependent inhibition of membrane-bound IL
      5Ralpha, upregulation of soluble IL-5Ralpha transcription, but no change in GM
      CSF receptor expression. These findings indicate that retinoids can
      differentially regulate membrane and soluble isoforms of IL-5Ralpha, and that
      these effects have functional consequences in vitro on eosinophil and basophil
      differentiation. ATRA may be of therapeutic benefit in allergic inflammatory
      disorders in which eosinophil differentiation and membrane-bound IL-5R are
      upregulated.

PMID- 11306983
TI  - Histamine-induced activation of human lung macrophages.
AB  - BACKGROUND: Histamine plays a central role in the pathogenesis of allergic and
      inflammatory diseases by modulating vascular and airway responses. Increasing
      evidence suggests that histamine also regulates the function of inflammatory and
      immune cells. Macrophages are primarily involved in inflammatory diseases of the
      lung. We explored the ability of low concentrations of histamine to induce the
      release of proinflammatory mediators from human lung macrophages. METHODS:
      Macrophages purified (> 95%) from lung parenchyma by Percoll density gradients
      and adherence to polystyrene dishes were incubated (37 degrees C, 2-24 h) with
      histamine (10(-9)-10(-6) M). At the end of incubation, the release of beta
      glucuronidase and IL-6 was determined. RESULTS: Histamine induced a concentration
      dependent release of beta-glucuronidase and IL-6 with a maximum release after 2
      and 6 h of incubation, respectively. Exocytosis induced by histamine was
      noncytotoxic and was Ca(2+)- and temperature-dependent. The effect of histamine
      was inhibited by the H(1) receptor antagonist fexofenadine but not by the H(2)
      antagonist ranitidine. CONCLUSIONS: These data indicate that histamine is an
      effective stimulus for exocytosis and cytokine production from human lung
      macrophages. These effects are inhibited by pharmacological concentrations of
      fexofenadine. Our results suggest that histamine may contribute to the long-term
      evolution of lung inflammation and tissue remodelling in allergic diseases by
      modulating the production of proinflammatory and immunoregulatory mediators by
      macrophages.

PMID- 11306984
TI  - Invited lecture: activation of the epithelial mesenchymal trophic unit in the
      pathogenesis of asthma.
AB  - BACKGROUND: A recent NIH Workshop and an ERS Task Force concluded that more work
      was needed to understand mechanisms of severe and chronic asthma. This report
      describes a series of studies that identify aberrant epithelial mesenchymal
      signalling in the airways as an important event in maintaining inflammation and
      driving remodelling in response to environmental injury. METHODS:
      Immunohistochemistry, genotyping and functional studies conducted on cultured
      asthmatic cells and mucosal biopsies were used to identify biochemical pathways
      involved in epithelial injury and repair in asthma and their relationship to
      disease severity. RESULTS: Our findings suggest that the asthmatic state results
      from an interaction between a susceptible epithelium and Th-2-mediated
      inflammation to alter the communication between the epithelium and the underlying
      mesenchyme - the epithelial mesenchymal trophic unit - leading to disease
      persistence, airway remodelling and refractoriness to corticosteroid treatment.
      CONCLUSIONS: Asthma is more than an inflammatory disorder, but requires
      engagement of important signalling pathways involved in epithelial repair and
      tissue remodelling. These pathways involving EGFRs and TGF-betaRs provide targets
      against which to develop novel therapies for chronic asthma.

PMID- 11306985
TI  - In vivo effects of apoptosis in asthma examined by a murine model.
AB  - BACKGROUND: One of the characteristic features of bronchial asthma is the
      accumulation of various inflammatory cells, predominantly eosinophils, at the
      subepithelial region beneath the basement membrane of the airway. Apoptosis is a
      form of physiological cell death, through which the cellular contents including
      biologically active substances are kept in the cell membrane and are removed
      without their harmful effects. So, attempts were made to clarify whether the
      induction of apoptosis is beneficial in asthma by using a murine model with
      ovalbumin (OA) as responsible allergen. METHODS: A/J mice, which are genetically
      predisposed to be hyperresponsive to acetylcholine, were immunized with OA and
      alum, accompanied by OA inhalation for 2 weeks, during which some of the mice
      were also treated with either anti-Fas monoclonal antibody or sham control
      hamster IgG intranasally. Airway responsiveness to acetylcholine was then
      analyzed by measuring airway resistance with a body plethysmograph box. Apoptosis
      was assessed by propidium iodide and TUNEL staining. RESULTS: Inhalation of OA
      increased both airway responsiveness to acetylcholine and the number of cells,
      mostly eosinophils, infiltrated into the airway. Administration of anti-Fas
      antibody induced apoptosis in the infiltrated eosinophils and abolished
      augmentation of airway hyperresponsiveness caused by OA inhalation. CONCLUSION:
      Induction of apoptosis in proinflammatory cells including eosinophils at the
      airway may have a beneficial effect on suppressing airway hyperresponsiveness.

PMID- 11306986
TI  - Airways hyperresponsiveness and the effects of lung inflation.
AB  - Lung inflation has a beneficial effect on the airways of healthy subjects. It
      acts as a bronchoprotector, that is to prevent bronchoconstriction, and as a
      bronchodilator, in that it reverses bronchial obstruction. The bronchoprotective
      effect of deep inspiration is more potent than the bronchodilatory one, and the
      two phenomena appear to advocate different mechanisms. Asthmatics and rhinitics
      with airways hyperresponsiveness show an impairment in bronchoprotection induced
      by deep breaths, whereas the bronchodilatory effect, although reduced, is still
      effective. The lack of the bronchoprotective effect of deep inspiration may
      contribute to the development of airways hyperresponsiveness. The mechanisms
      through which lung inflation exerts its beneficial role in healthy subjects, and
      the factors impairing such an effect in those with airways hyperresponsiveness,
      are currently under investigation.

PMID- 11306987
TI  - Characteristics of the Inflammatory response in bronchial lavage fluids from
      patients with status asthmaticus.
AB  - Status asthmaticus (SA) is a sudden respiratory failure characterized by an acute
      bronchospasm with a severe inflammation, requiring in some cases mechanical
      ventilation (MV). Initial postmortem studies emphasized the presence of
      eosinophils in the bronchial wall and of mucus plugs filling the bronchi. More
      recently a prominent neutrophil influx was observed in patients with fatal or
      near fatal asthma. The aim of our study was to evaluate characteristics of
      bronchial inflammation in terms of cellular influx, mediators, cytokines and
      chemokines. Ten patients with SA were compared with 11 patients with chronic
      asthma, 4 without preexisting pulmonary disease requiring MV and 8 healthy
      subjects. Bronchial lavages in SA were indicated to remove bronchial plugs in
      case of atelectasis and/or refractory SA. The main findings in patients with SA
      were a massive influx of neutrophils (81.5 +/- 4.5%) with a dramatic increase of
      neutrophil elastase. Although more limited than the neutrophil influx,
      eosinophils were present and associated with high levels of eosinophil cationic
      protein (ECP), which suggested that a part of the eosinophils were activated and
      degranulated. In parallel to the neutrophil and eosinophil influx, we observed
      elevated amounts of proinflammatory (IL-1beta, IL-5, IL-6, TNFalpha) and anti
      inflammatory (IL-10, IL-1 receptor antagonist, soluble TNF receptors) cytokines
      with a balance in favor of a net proinflammatory activity. Chemokines were also
      present in large quantities with a predominance of MCP-1, MIP-alpha and RANTES
      with a significant correlation between MCP-1, RANTES, IL-5 and both eosinophil
      and ECP values. In addition an acute 10- to 160-fold increase of 92-kD gelatinase
      (MMP9) was detected in bronchial lavage fluid from patients with SA associated
      with a free metallogelatinolytic activity, suggesting an imbalance in the local
      production of proteases and antiproteases. Therefore, our results indicate that
      the bronchi in SA are the site of an intense production of pro- and anti
      inflammatory cytokines and chemokines that are implicated in the influx of
      eosinophils and neutrophils. The inflammatory pattern in SA clearly differs from
      the usual profile observed in chronic asthma.

PMID- 11306988
TI  - Mechanisms of T cell peptide epitope-dependent late asthmatic reactions.
AB  - Short peptide sequences corresponding to T cell epitopes have been identified in
      the major cat allergen Fel d 1. In order to directly activate allergen-specific T
      cells in cat-allergic asthmatic individuals, peptides were administered by
      intradermal injection. Subsequently, a proportion of subjects experienced a
      delayed reduction of airway calibre manifested as a decrease in FEV(1). Changes
      in lung function occurred approximately 3 h after peptide injection, peaked at 6
      h and resembled an isolated late asthmatic reaction (LAR). Using molecular tissue
      typing techniques, it was determined that many of the individuals experiencing
      isolated LAR expressed particular HLA-DR molecules. These molecules were shown in
      subsequent experiments to bind individual peptides within the preparation and
      thus to activate T cells in a major histocompatibility complex (MHC)-restricted
      fashion. The precise mechanisms whereby MHC-restricted activation of allergen
      specific T cells gives rise to bronchoconstriction are currently under
      investigation.

PMID- 11307006
TI  - New aspects of itch pathophysiology: component analysis of atopic itch using the
      'Eppendorf Itch Questionnaire'.
AB  - Itch represents a leading symptom in dermatological practice with many
      psychophysiological aspects. Instruments for qualitative registration of these
      central nervous factors and evaluation of therapeutic measures are still missing.
      We analyzed in detail the subjective itch sensation in 108 patients with acute
      atopic eczema with a new questionnaire developed in analogy to the McGill pain
      questionnaire. The descriptors with the highest load in atopic itch and the most
      frequent reaction patterns in atopic eczema patients were identified. Itch
      intensity (mean VAS 62%) and eczema severity (SCORAD mean 41 points) showed a
      different frequency distribution pattern with a correlation of r = 0.33 (p <
      0.05). Principal component analysis of the itch questionnaire data was performed
      and compared with the standardized SCORAD severity index for the patients with
      atopic eczema. Three main factors of atopic itch explained 58% of the total
      variance: (1) 'suffering' (correlation with SCORAD, r = 0.6); (2) 'phasic
      intensity' (correlation with SCORAD, r = 0.4), and (3) 'ecstatic' component
      (associated with certain active reaction patterns). In conclusion, the complete
      description of itch has to consider different factors, which may be described on
      a more general level by three main components. Two of these are correlated with
      objective criteria of disease activity.

PMID- 11307007
TI  - Homing receptor expression on cord blood T lymphocytes and the development of
      atopic eczema in infants.
AB  - Expression of the gut-homing receptor integrin alphaEbeta7, but not cutaneous
      lymphocyte-associated antigen (CLA), on milk allergen-stimulated cord blood T
      lymphocytes precedes the development of milk-induced eczema in early infancy. The
      data indicate the involvement of integrin alphaEbeta7 in the development of
      infantile allergic eczema and provide a clue to the avoidance of specific
      allergens and novel therapy targeting homing receptors in food allergy.

PMID- 11307008
TI  - Pathogenesis of drug-induced exanthema.
AB  - BACKGROUND: In vitro data derived from drug-specific T cell clones have revealed
      that heterogeneous T cell subsets with distinct phenotypes (CD4+ > CD8+) and cell
      functions (strong IL-5 production, cytotoxic potential) are generated. The aim of
      this study was to elaborate the relevance of these findings in vivo. METHODS:
      Skin biopsy specimens from drug-induced maculopapular exanthema and normal skin
      were analyzed for CD4, CD8, CD25, HLA-DR, CD54, perforin, granzyme B, IL-5 and
      IFN-gamma using immunohistochemistry. RESULTS: The majority of infiltrating
      lymphocytes in maculopapular drug eruptions were CD4+. Both CD4+ and CD8+ T cells
      expressed perforin and granzyme B and were partly located at the dermoepidermal
      junction and in the epidermis. In addition, strong immunoreactivity for IL-5 and
      moderate immunoreactivity for IFN-gamma were observed in the mononuclear cell
      infiltrate. CONCLUSIONS: Our data indicate that skin infiltrating T cells with a
      cytotoxic potential and the ability to produce IL-5 and IFN-gamma may contribute
      to the damage of keratinocytes and the activation of eosinophils, which are
      typical features of drug-induced maculopapular exanthema.

PMID- 11307009
TI  - Activation of the plasma kinin forming cascade along cell surfaces.
AB  - Proteins of the plasma kinin-forming cascade bind to endothelial cells and
      activation of the cascade can be initiated along the surface. The light chain of
      high molecular weight kininogen (HK) (domain 5) and factor XII bind to gC1qR, the
      heavy chain of HK (domain 3) binds to cytokeratin 1 and the interactions are zinc
      dependent. Prekallikrein binds to domain 6 of HK. Antisera to gC1qR and
      cytokeratin 1 inhibit binding and activation. Incubation of normal plasma with
      endothelial cells leads to gradual conversion of prekallikrein to kallikrein,
      while plasma deficient in factor XII or HK are inactive within a 2-hour time
      frame. Thus factor XII is critical for activation to proceed. Augmentation of
      these reactions may occur when C1 inhibitor is functionally deficient or with ACE
      inhibitors which also inhibit kininases.

PMID- 11307025
TI  - Mucosal tolerance induction with hypoallergenic molecules in a murine model of
      allergic asthma.
AB  - Type I allergy, frequently elicited by airborne allergens, has constantly
      increased within recent years. Birch pollen and its major allergen Bet v 1
      represent a major source of type I allergens. By genetic engineering
      hypoallergenic Bet v 1 fragments were produced, which lost the IgE binding
      capacity but retained the T cell epitopes. We have established a murine model of
      aerosol sensitization to birch pollen and its major allergen Bet v 1, leading to
      type I allergic immune responses and airway hyperresponsiveness. In the present
      study we demonstrate that mucosal administration of recombinant Bet v 1 prior to
      sensitization led to allergen-specific suppression of B and T cell responses in
      vivo and in vitro, reduction of eosinophilic infiltration in the lungs and
      inhibition of airway hyperresponsiveness. Intranasal pretreatment with the
      nonanaphylactic fragments of Bet v 1 prevented allergic immune responses and
      airway inflammation to the same degree as the pretreatment with the complete
      molecule. We conclude from our studies that mucosal tolerance induction with
      hypoallergenic molecules could provide a safe and convenient treatment strategy
      against type I allergies.

PMID- 11307026
TI  - IgE mimotopes of birch pollen allergen Bet v 1 induce blocking IgG in mice.
AB  - BACKGROUND: The induction of nonanaphylactogenic 'blocking' IgG antibodies
      capable of inhibiting the IgE/allergen interaction represents a favorable
      therapeutic concept for type I allergy. However, IgG antibodies to allergens may
      block or enhance specific IgE binding, depending on the recognized epitope.
      Taking the major birch pollen allergen Bet v 1 as a model, we developed a
      strategy for the precise induction of IgG antibodies of a desired epitope
      specificity. METHODS: Random phage display peptide libraries were applied to
      define peptide structures mimicking natural epitopes (mimotopes) of Bet v 1.
      Selections were performed with BIP 1, a murine monoclonal antibody known to
      enhance the IgE binding to Bet v 1, and with anti-Bet v 1 IgE purified from
      patients' sera. The characterized Bet v 1 mimotopes were used to localize the
      corresponding epitope at the surface of Bet v 1 by a computer-aided mathematical
      approach based on the three-dimensional structure and the chemical character of
      the amino acids. The Bet v 1 mimotopes were further used to immunize BALB/c mice.
      The specificity of the induced antibodies was tested by immunoblotting and
      inhibition assays. RESULTS: With the three-dimensional epitope search it became
      possible to localize a discontinuous IgE epitope on the surface of Bet v 1 in a
      substantial distance from the IgG epitope of the monoclonal antibody BIP 1.
      Moreover, we could demonstrate that phage displaying mimotopes are immunogenic
      vectors for the precise induction of epitope-specific IgG. Immunization with BIP
      1 mimotopes induced IgG enhancing the IgE binding to Bet v 1, whereas
      immunization with IgE mimotopes resulted in IgG capable of blocking human IgE
      binding in vitro. CONCLUSION: Allergen mimotopes can be used for the induction of
      anti allergen IgG of desired specificity. We propose that mimotope immunotherapy
      based on IgE mimotopes generated by biopannings may represent a future concept
      for therapy of type I allergy.

PMID- 11307027
TI  - Nonallergenic peptides from surface-exposed areas or B-cell epitopes of allergens
      for specific immunotherapy.

PMID- 11307028
TI  - Humanized anti-IgE mAb Hu-901 prevents the activation of allergen-specific T
      cells.
AB  - BACKGROUND: As a result of the very efficient capture of allergens by IgE that
      focuses to CD23 on B cells or FcepsilonRI on dendritic cells, allergen-specific T
      cells can be activated after exposure to very low levels of allergens. This IgE
      mediated allergen presentation is 100- to 1,000-fold more efficient than fluid
      phase endocytosis. The aim of the present study was to determine whether
      humanized anti-IgE mAb Hu-901 can prevent the activation of allergen-specific T
      cells by inhibiting IgE-mediated allergen presentation. METHODS: A house dust
      mite major allergen Der p 1-specific T cell line was generated from an allergic
      asthma patient, and a model was set up to show IgE-facilitated allergen
      presentation via CD23 on EBV-transformed B cells. In addition, experiments were
      performed by FACS analysis, detecting the presence of IgE-allergen complexes
      bound to EBV-B cells by polyclonal FITC-labeled anti-IgE antisera. RESULTS: The
      anti-IgE mAb Hu-901 inhibited proliferation of allergen-specific T cells at low
      allergen concentrations. Inhibition was dose-dependent. This effect could be
      explained by Hu-901 inhibition of binding of allergen-IgE complexes to CD23
      expressed on EBV-transformed B lymphocytes. CONCLUSIONS: These data clearly
      indicate that anti-IgE antibodies for the treatment of allergy exert their effect
      not only by inhibiting mast cell/basophil degranulation, but also by preventing T
      cell activation, which possibly explains the effect of anti-IgE treatment on late
      phase reactions noted in clinical studies.

PMID- 11307029
TI  - Mosquito allergy: recombinant mosquito salivary antigens for new diagnostic
      tests.
AB  - In patients with mosquito allergy, lack of a readily available, sensitive,
      specific, safe test is the major obstacle to accurate diagnosis. Three
      recombinant mosquito salivary antigens, rAed a 1 (68 kD), rAed a 2 (37 kD) and
      rAed a 3 (30 kD), from Aedes aegypti have been cloned, expressed, purified and
      characterized. All three recombinant antigens are shared by Aedes vexans and
      other mosquito species, and all have been found to have biologic activity in
      humans. In recent studies, 43% of 28 mosquito bite test-positive subjects had a
      positive skin test to rAed a 1, 11% to rAed a 2 and 32% to rAed a 3. The sizes of
      the skin test reactions to the recombinant antigens correlated with the sizes of
      the A. aegypti bite test reactions. None of 15 A. aegypti bite test-negative
      subjects had a positive skin test to any of the recombinant antigens. Recombinant
      mosquito salivary antigens will facilitate the diagnosis of mosquito allergy.

PMID- 11307030
TI  - The influence of CpG motifs on a protein or DNA-based Th2-type immune response
      against major pollen allergens Bet v 1a, Phl p 2 and Escherichia coli-derived
      beta-galactosidase.
AB  - BACKGROUND: DNA immunization and protein immunization with CpG motifs as
      adjuvants represent promising approaches in allergen-specific immunotherapy.
      OBJECTIVE: We investigated the effect of coinjection or prepriming with CpG-ODN
      on Th2-type responses induced by gene gun and protein immunization. METHODS:
      BALB/c mice were immunized with the gene gun using plasmid DNA containing the
      cDNAs coding for the genes of Bet v 1a, Phl p 2 and beta-galactosidase or with
      the purified Al(OH)(3)-adsorbed proteins. In addition, CpG-ODN were applied by
      coinjection or by prepriming treatment. Antibody and cytokine responses were
      measured by ELISA, proliferative and cytotoxic responses were determined by
      standard labeling procedures. Furthermore, the allergenic activity of sera was
      measured by passive cutaneous anaphylaxis. RESULTS: Gene gun immunization and
      protein immunization induced a clear Th2-type response for all antigens. The Th1
      promoting effect of CpG-ODN coinjection together with gene gun immunization was
      restricted to beta-galactosidase as indicated by the increase of IgG2a and a
      marked expression of IFN-gamma. CpG motifs also increased the specific cytotoxic
      response against beta-galactosidase. Prepriming with CpG-ODN and gene gun or
      protein immunization with Bet v 1a exhibited no significant difference to the non
      CpG control group. However, sera from mice preprimed with CpG-ODN induced no
      anaphylaxis with gene gun immunization, but with protein immunization.
      CONCLUSIONS: The effect of CpG motifs in vivo depends on a variety of parameters
      like the nature of the antigen and the immunization modality. Furthermore, our
      studies indicate that a combination of CpG + DNA immunization may be more
      effective in antagonizing Th2 responses than the combination of CpG + protein
      immunization.

PMID- 11307031
TI  - Allergic manifestations as the results of a conditional autoimmune response.
AB  - By means of repertoire cloning we have isolated human anti-IgE antibodies as well
      as human anti-FcepsilonRI antibodies. Whether the naturally occurring anti-IgE
      autoantibodies play a pathophysiological role may be disputed, but the beneficial
      role of recombinant anti-IgE antibodies as a therapeutic agent has been shown. On
      the other hand, the natural antibodies isolated from an antibody library of a
      nonallergic individual against the FcepsilonRI alpha-chain are anaphylactogenic,
      if FcepsilonRI was not occupied. Thus, anti-FcepsilonRI autoantibodies may be
      part of a conditional autoimmune reaction, leading to urticaria if local IgE is
      consumed, e.g. after an immediate reaction. Thus, anti-FcepsilonRI antibodies may
      represent an amplification arm of the late reaction. The normal occurrence of
      anti-IgE and anti-IgE receptor autoantibodies may suggest that it might also be
      feasible to induce such autoantibodies by vaccination. In a monkey model using a
      mimotope of human IgE it was possible to induce a beneficial anti- IgE autoimmune
      response. The actual epitope of the IgE molecule was then also molecularly
      reconstructed by generating recombinant anti-idiotypic antibodies. These
      antibodies also induced effectively an anti-IgE response in monkeys, suggesting
      that not only mimotopes but also anti-idiotypic antibodies may be used to
      generate an autoimmune response. Both of our projects suggest that active
      immunization may be a new form of immunomodulation for the treatment of allergic
      disease.

PMID- 11307032
TI  - Step-down and step-up therapy in moderate persistent asthma.
AB  - BACKGROUND: A step-down therapy may be more beneficial for the management of
      asthma than a step-up therapy. METHODS: Eighty-two asthmatic patients with
      moderate persistent asthma were enrolled in the study and randomized into three
      groups. One group of patients received 400 microg/day of beclomethasone
      dipropionate (BDP) for 4 weeks and then 800 microg/day for another 4 weeks (step
      up group). The other two groups of patients received 1,200 microg/day of BDP for
      4 weeks with or without short-term oral steroid (prednisolone, 0.5 mg/day for 1
      week) and then 800 microg/day for another 4 weeks (step-down group). Severe
      exacerbation of asthma, asthma symptoms, respiratory function and rescue use of
      inhaled beta(2)-agonists were monitored. If asthma was well controlled, the dose
      of BDP was decreased every 3 months and if asthma was exacerbated, the dose of
      BDP was increased until 8 months after the initial treatment. RESULTS: Twenty-two
      patients during the run-in period, 4 patients in the step-up group, 2 patients in
      the step-down group treated with a high dose of BDP and no patients in the step
      down group with oral steroids during first 4 weeks dropped out because of severe
      exacerbation of asthma. Although asthma symptoms and respiratory function
      significantly improved 8 weeks after the therapy in all groups, more significant
      and prompt improvements of these parameters were observed in patients of the step
      down group than in patients of the step-up group after the first 2 weeks of
      treatment. Furthermore, step-down therapy with short-term oral steroid resulted
      in the lowest maintenance doses of BDP at 8 months of the three groups.
      CONCLUSIONS: These results suggest that step-down therapy starting with a high
      dose of inhaled steroid and short-term oral steroid is more effective in gaining
      prompt control of asthma and reducing the severe exacerbation of asthma and the
      maintenance dose of inhaled steroids than a step-up therapy starting with a low
      dose of inhaled steroids in patients with moderate persistent asthma.

PMID- 11307033
TI  - Regulation of gonadotropin-releasing hormone (GnRH) gene expression during GnRH
      neuron migration in the mouse.
AB  - The mechanisms underlying the migration of the gonadotropin-releasing hormone
      (GnRH) neurons from the nose into the forebrain are not resolved. In an attempt
      to characterize further the migrating GnRH neurons, we have employed in situ
      hybridization techniques and transgenic mouse models to examine levels of GnRH
      mRNA and GnRH gene transcription in GnRH neurons during migration in the mouse.
      In the first experiment, cellular levels of GnRH mRNA in neurons located
      throughout the nose and forebrain were examined in embryonic day (E) 12.5, 14.5,
      16.5 and 19.5 mice using in situ hybridization. The GnRH mRNA content of cells
      located in both the nose (p < 0.01) and forebrain (p < 0.05) was found to
      increase significantly from E12.5 to E19.5 and from E14.5 to E19.5, respectively.
      However, cellular levels of GnRH mRNA were not significantly different in neurons
      located in the nose compared with the brain at each developmental age. In the
      second experiment, levels of GnRH gene transcription were investigated at E14.5
      using two different GNLZ transgenic mouse lines in which 13.5 kb of GnRH gene
      sequences direct the expression of the LacZ reporter to the nucleus of GnRH
      neurons. Migrating GnRH neurons displayed up to a 3-fold increase (p < 0.01) in
      transgene expression, an index of GnRH transcription, precisely as they
      approached and entered the forebrain. These results indicate that GnRH gene
      expression in migrating GnRH neurons is likely regulated by temporal as well as
      spatial factors and that, as found postnatally, this may involve both
      transcriptional and post-transcriptional regulatory mechanisms.

PMID- 11307034
TI  - Immortalized gonadotropin-releasing hormone neurons (GT1-7 cells) exhibit
      synchronous bursts of action potentials.
AB  - Although it has been assumed that synchronized firing of gonadotropin-releasing
      hormone (GnRH) neurons is necessary for pulsatile GnRH secretion, there is no
      clear evidence for this. In the present study we simultaneously recorded
      spontaneous action potentials from multiple cells. Immortalized GnRH neurons (GT1
      7 cells) were cultured on a multi-electrode dish (MED) and action potentials
      recorded by an extracellular recording method. One to two weeks after the
      beginning of culture, spontaneous action potentials appeared, exhibiting bursts
      composed of 5-10 action potentials. Burst activity was intermittent and periodic
      with mean burst intervals of 13.3 s. Furthermore, burst activity was recorded
      almost simultaneously from several micro-electrodes, suggesting that electrical
      activities of GT1-7 cells were synchronized with each other. Periodic bursts were
      completely and reversibly blocked by 1-5 microM tetrodotoxin, indicating that
      voltage-dependent Na(+) channels are involved in their generation. gamma
      Aminobutyric acid (GABA) given at a 10-microM concentration shortened inter-burst
      intervals, whereas 10 microM bicuculline lengthened them. Finally, the gap
      junctional blockers n-octyl alcohol (1 mM) and carbenoxolone (100 microM)
      reversibly blocked periodic burst activity. The present study provides direct
      evidence that the electrical activity of GT1-7 cells exhibits synchronous and
      periodic bursts composed of action potentials. In addition, endogenous GABA is
      involved in GT1-7 cells in determining burst frequency. Although the precise
      mechanism of synchronized burst activities needs to be clarified, gap junctional
      communications among GT1-7 cells are at least partially involved.

PMID- 11307035
TI  - Estrogens act in rat hippocampus and frontal cortex to produce rapid, receptor
      mediated decreases in serotonin 5-HT(1A) receptor function.
AB  - Previously our laboratory has shown that 17beta-estradiol in vivo rapidly
      decreases R(+)-8-OH-DPAT-stimulated [(35)S]GTPgammaS binding (a measure of the
      initial biochemical event in the intracellular signaling pathway associated with
      5-HT(1A) receptors) in the hippocampus, frontal cortex and amygdala. Studies were
      designed to determine if 17beta-estradiol also acts in vitro on estrogen
      receptors in the hippocampus and frontal cortex to decrease 5-HT(1A) receptor
      function. Hippocampus and frontal cortex were dissected from ovariectomized rats
      and incubated for up to 3 h with various estrogens and antiestrogens; membrane
      homogenates were prepared for R(+)-8-OH-DPAT-stimulated [(35)S]GTPgammaS binding
      assays. 17beta-Estradiol (10(-6) M) decreased the maximal response in the R(+)-8
      OH-DPAT-stimulated [(35)S]GTPgammaS binding assay in a time-dependent manner
      (observed at 30, 60 and 120 min) in both hippocampus and frontal cortex. The
      hormone, however, did not alter the EC(50) of R(+)-8-OH-DPAT. When hippocampus
      and frontal cortex were incubated in graded concentrations of 17beta-estradiol
      for 1 h, the calculated EC(50) was approximately 2.5 x 10(-8) M in both brain
      regions. The nonestradiol estrogen diethylstilbestrol also decreased 5-HT(1A)
      receptor function while the less potent estrogens 17alpha-estradiol and estriol
      were inactive at 5 x 10(-8) M. The estrogen receptor antagonist ICI 182,780
      potently and completely blocked the effects of 17beta-estradiol on 5-HT(1A)
      receptor function with an apparent K(B) of approximately 10(-9) M. These data
      demonstrate clearly that estrogens can act on estrogen receptors located in
      hippocampus and frontal cortex of ovariectomized rats to produce rapid
      heterologous decreases in 5-HT(1A) receptor function.

PMID- 11307036
TI  - Lactation alters gamma-aminobutyric acid neuronal activity in the hypothalamus
      and cerebral cortex in the rat.
AB  - Gamma-aminobutyric acid (GABA) neurons terminating in the hypothalamus have been
      implicated in the neuroendocrine regulation of reproductive hormones,
      particularly luteinizing hormone (LH) and prolactin. The aim of this study was to
      examine whether GABAergic neuronal activity in the hypothalamus was modified
      during lactation, and whether any observed changes correlated with changes in
      secretion of these hormones. Animals were divided into three experimental groups:
      diestrous controls, lactating with pups present (with pups), and lactating with
      pups removed for 4 h (without pups). Animals were decapitated either without
      treatment, or 60 min after inhibition of GABA degradation by aminooxyacetic acid
      (AOAA) (100 mg/kg, i.p.). The rate of GABA accumulation in the tissue after AOAA
      is a measure of GABA turnover. GABA turnover was estimated in 13 microdissected
      brain regions, and serum prolactin and LH measured by radioimmunoassay. Suckling
      was associated with significantly increased prolactin and significantly decreased
      LH compared with diestrous rats. In lactating rats with pups, GABA turnover was
      significantly increased in the cingulate cortex compared with diestrous rats.
      GABA turnover was significantly increased in the ventrolateral preoptic nucleus
      of lactating rats with pups compared with diestrous rats or lactating rats
      without pups. There was significantly lower GABA turnover in the anterior
      hypothalamic area, ventromedial and dorsomedial hypothalamic nuclei in lactating
      rats without pups compared with diestrous rats. There were no significant changes
      in other brain regions examined. The results demonstrate that activity of
      GABAergic neurons in specific parts of the hypothalamus and cerebral cortex is
      altered during lactation.

PMID- 11307037
TI  - Hypothalamo-pituitary-adrenal axis sensitization after chronic salt loading.
AB  - Hypothalamic parvocellular vasopressin (VP) and corticotropin-releasing hormone
      (CRH) in the paraventricular nucleus (PVN) are major secretagogues of
      corticotropin (ACTH), and central plasticity including their alteration is
      closely related to hypothalamic-pituitary-adrenal (HPA) axis modulation. Chronic
      hyperosmotic stress caused by 2% salt loading has been known to alter VP and CRH
      expression. We recently reported that rehydration, a recovery stage from salt
      loading, induced a prolonged increase in parvocellular VP mRNA expression and
      suggested that rehydration can modulate HPA axis function without obvious
      external stress. In the present study, we examined hypothalamic VP and CRH mRNA
      expression and their responsiveness to acute immobilization stress in control,
      salt-loaded and rehydrated animals, in order to clarify the precise mechanism of
      HPA axis regulation during rehydration. The results were further compared with
      plasma corticosterone and ACTH levels. Plasma corticosterone decreased during
      salt loading, whereas it increased during rehydration at 1 week. Basal ACTH
      concentration increased in 1-week-rehydrated animals, with enhanced
      responsiveness to the acute immobilization stress. In the hypothalamic
      parvocellular PVN, basal CRH mRNA levels also decreased during salt loading and
      increased during rehydration. Basal VP mRNA was up-regulated during both salt
      loading and rehydration. VP mRNA responded to additional acute stress during salt
      loading and rehydration, but CRH mRNA did not. These results indicate that the
      HPA axis activity of parvocellular neurons is still altered at 1 week of
      rehydration and that VP plays a dominant role in regulating ACTH release in
      response to acute stress. This rehydration stage may thus be a good model for
      analysis of post-stress sensitization of the HPA axis.

PMID- 11307038
TI  - Prenatal glucocorticoid modifies hypothalamo-pituitary-adrenal regulation in
      prepubertal guinea pigs.
AB  - We hypothesized that exposure to synthetic glucocorticoid during rapid brain
      growth (d50-52, birth = 68 days) in fetal guinea pigs modifies hypothalamo
      pituitary-adrenal (HPA) function after birth, and that this involves changes in
      central corticosteroid receptor regulation. On the basis of our previous studies,
      we proposed that this effect is sex-specific. Pregnant guinea pigs were treated
      with dexamethasone (1 mg/kg) or vehicle on d50-51 of gestation, and juvenile
      offspring were euthanized at rest or following isolation stress on postnatal day
      18. Dexamethasone increased the length of gestation (1.5 days) and altered body
      and organ (brain, heart, adrenal) growth. Resting plasma cortisol concentrations
      were significantly elevated in young male, but not female guinea pigs exposed to
      dexamethasone as fetuses. In female offspring born to dexamethasone-treated
      mothers, cortisol responses to isolation stress were attenuated. In males,
      elevated basal cortisol levels were not increased further by isolation. In the
      brain, hippocampal glucocorticoid receptor (GR) mRNA levels were significantly
      lower (10-25%) in females exposed to dexamethasone in utero. In contrast, GR mRNA
      levels were elevated (10-20%) in males from this prenatal treatment group.
      Mineralocorticoid receptor mRNA in the limbic system and GR mRNA levels in the
      pars distalis were unaffected. Pro-opiomelanocortin mRNA was significantly lower
      (30%) in the male pars intermedia following dexamethasone exposure. In
      conclusion, prenatal glucocorticoid exposure affects growth and HPA function as
      well as limbic and hypothalamic GR expression in juvenile offspring, and these
      effects are highly sex-specific.

PMID- 11307039
TI  - Central bombesin activates the hypothalamic-pituitary-adrenal axis. Effects on
      regional levels and release of corticotropin-releasing hormone and arginine
      vasopressin.
AB  - While corticotropin-releasing hormone (CRH) is a primary regulator of the
      hypothalamic-pituitary-adrenal (HPA) axis, the mechanism(s) triggering the
      release of this corticotropin (ACTH) secretagogue remains unknown. Stressful and
      appetitive events evoke the release of not only CRH but also of bombesin (BN)
      like peptides. Furthermore, CRH antagonists attenuate the endocrine and
      behavioral effects of BN, suggesting that BN-like peptides may mediate their
      effects via CRH release. An initial (mapping) study revealed that centrally
      administered BN (0.25 or 0.5 microg i.c.v.) increased circulating corticosterone
      and ACTH levels and decreased immunoreactive (ir)-CRH at the nucleus of the
      solitary tract, ventromedial (VMH) and anterior hypothalamic nuclei, and the
      central amygdaloid nucleus. Whereas BN treatment decreased ir-vasopressin (AVP)
      at the VMH, it elevated levels of this peptide in the hypothalamic
      paraventricular and median eminence/arcuate (Me/Arc) regions. Dynamic, in vivo
      release experiments (using push-pull perfusion) revealed that BN evoked the
      release of ir-CRH and ir-AVP from the Me/Arc and increased interstitial levels of
      these secretagogues at the anterior pituitary. These results suggest that BN-like
      peptides may regulate certain hypothalamic and extrahypothalamic circuits,
      including the HPA axis, by affecting regional utilization of ir-CRH and ir-AVP,
      and/or by provoking the release of these peptides at the Me/Arc, thus increasing
      their availability downstream at the anterior pituitary and increasing
      circulating ACTH and corticosterone levels.

PMID- 11307040
TI  - Glutamatergic influences on the basal ganglia.
AB  - Glutamate is the predominant excitatory neurotransmitter of the basal ganglia,
      where it acts on ionotropic and metabotropic receptors. In the best studied of
      the basal ganglia disorders, Parkinson's disease, there is compelling evidence
      that the activities of glutamatergic pathways are altered. Of particular
      importance, the glutamatergic subthalamic nucleus becomes overactive.
      Pharmacologic blockade of subthalamic neurotransmission has antiparkinsonian
      symptomatic effects and may also help to protect the remaining dopamine neurons
      of the substantia nigra from excitotoxic neurodegeneration. Development of drugs
      to manipulate the glutamatergic system with appropriate pharmacologic and
      anatomic selectivity is likely to dramatically improve our ability to treat
      disorders of the basal ganglia.

PMID- 11307041
TI  - Pharmacokinetic and pharmacodynamic analysis of sedative and amnesic effects of
      lorazepam in healthy volunteers.
AB  - This study describes for the first time the pharmacokinetic and pharmacodynamic
      modeling of the psychomotor and amnesic effects of a single 2-mg oral dose of
      lorazepam in healthy volunteers. Twelve healthy volunteers were included in this
      randomized, double-blinded, placebo-controlled two-way crossover study. The
      effect of lorazepam was examined for a battery of tests that explored mood,
      vigilance, psychomotor performance, and memory. The pharmacokinetic and
      pharmacodynamic modeling of these tests was performed using the indirect response
      model. Vigilance and psychomotor performance were significantly impaired. Short
      term memory was not affected, but a paradoxical tendency to improvement of the
      score was observed 0.4 hours after drug intake. Significant impairment was
      observed for immediate and delayed cued verbal recall, for immediate and delayed
      free recall, and for picture recognition as well as for visual-verbal recall, but
      not for cued visual-spatial recall or priming. Globally, the different effects
      were greatest between 0.4 to 3 hours after dosing. However, the time course
      profile of the recovery period suggests a possible dissociation between the
      kinetics of the effects of lorazepam on vigilance, psychomotor performance, and
      visual episodic memory, on the one hand, and on verbal episodic memory, on the
      other. The pharmacokinetic and pharmacodynamic model used two compartments with
      first-order absorption to describe the lorazepam concentrations and an indirect
      response model with inhibition or stimulation of Kin to describe the effects. The
      mean values for calculated median effective concentration (EC50) derived from the
      pharmacokinetic and pharmacodynamic modeling of the different tests ranged from
      11.3 to 39.8 ng/mL. According to these EC50 values, lorazepam seemed to be more
      potent on the delayed-recall trials than on the immediate-recall trials; similar
      observations were made concerning the free-recall versus cued-recall trials. The
      previously stated results suggest that the tests performed in this study
      represent sensitive measurements of the effects of lorazepam on the central
      nervous system. Moreover, the parameter values derived from pharmacokinetic and
      pharmacodynamic modeling, especially, the EC50 values, may provide sensitive
      indices that can be used to compare the central nervous system effects of
      benzodiazepines.

PMID- 11307042
TI  - Multiple-dose tolerability, pharmacodynamics, and pharmacokinetics of the
      quinolizinone hypnotic Ro 41-3696 in elderly subjects.
AB  - The objectives of this double-blind, placebo-controlled study were to assess the
      multiple-dose tolerability, pharmacodynamics, and pharmacokinetics of the
      hypnotic agent Ro 41-3696 in elderly men and women (55-75 y of age). On day 1 and
      days 3-8, doses of 1, 3, 5, and 10 mg were administered sequentially to 4 groups
      of 10 subjects, 2 of whom received placebo. Psychomotor performance tests
      (tracking and attention) were conducted just before and at 1.5, 4, and 8 hours
      after drug intake on days 1, 4, 6, and 8. Memory was assessed at 24 hours after
      drug intake on days 1 and 8 by recall of a list of 10 words, which had been
      learned at 2 hours after intake. Ro 41-3696 was well tolerated at all dose
      levels. One subject dropped out of the study because of a hypersensitive skin
      reaction during treatment with 10 mg. Performance in both a tracking test and a
      memory search test was significantly affected by a dose of 10 mg and moderately
      affected by doses of 3 and 5 mg. The results of the 1-mg dose were
      indistinguishable from those of placebo. Long-term memory, as assessed by a word
      learning and recall test, showed the same pattern. Partial tolerance to the
      impairing effects in the psychometric tests developed over the course of
      treatment. Pharmacokinetics of both Ro 41-3696 and its O-desethyl metabolite Ro
      41-3290 were dose proportional and time independent. Ro 41-3696 was absorbed and
      eliminated rapidly (time of maximum plasma concentration, approximately 1 hour;
      elimination half-life, approximately 2 hours). Plasma levels of Ro 41-3290 were
      higher than those of the parent drug, and it was more slowly eliminated (values
      for time of maximum plasma concentration and elimination half-life, approximately
      2 and approximately 7 hours, respectively).

PMID- 11307043
TI  - Levodopa-induced drowsiness in healthy volunteers: results of a choice reaction
      time test combined with a subjective evaluation of sedation.
AB  - The aim of the present study was to assess levodopa (L-Dopa)-induced drowsiness
      in healthy volunteers using two parameters: choice reaction time and a subjective
      rating of sedation. Sixteen subjects participated in a randomized, double
      blinded, crossover study. A single dose of 200 mg L-Dopa or placebo was
      administered at 9:00 AM. To limit peripheral side effects connected with L-Dopa,
      subjects were treated with 20 mg domperidone three times daily. Subjective rating
      of sedation consisted of visual analogue scale. Reaction time was measured by
      means of responses to two light-emitting diodes. The illumination of one of these
      diodes constituted the imperative signal. Manual responses were performed on two
      buttons located under the right and left index fingers. Results demonstrated a
      positive correlation between sedation level and reaction time (r = 0.70, p =
      0.0026). Adverse events of L-Dopa were nausea (four cases) and excitation (one
      case). Subjects who did not develop adverse events were faster under L-Dopa than
      under placebo (p = 0.02), whereas subjects who had nausea or excitation were
      slower. A single dose of L-Dopa either deteriorated or improved choice reaction
      time in healthy volunteers according to whether it was sedative and whether it
      generated disruptive adverse events.

PMID- 11307044
TI  - The pharmacokinetic profile of the "first ever" oral dose of levodopa in de novo
      patients with Parkinson's disease.
AB  - To understand the delay in the clinical benefit that commonly occurs after
      initiation of levodopa (L-Dopa) treatment, we examined the pharmacokinetic
      profile of L-Dopa after the first oral dose ever taken of L-Dopa/carbidopa in
      untreated patients with Parkinson's disease and followed these parameters after 1
      month of treatment. This was performed in correlation with the clinical
      therapeutic effect. Plasma levels of L-Dopa were measured with use of high
      performance liquid chromatography with electrochemical detection after
      administration of the "first ever" 125 mg L-Dopa/12.5 mg carbidopa tablet in 15
      patients with de novo Parkinson's disease (mean age, 69 +/- 11 y, mean disease
      duration, 1.5 +/- 0.8 years). Blood samples were drawn before administration and
      thereafter at various intervals for a period of 4 hours. Repeated measurements
      after the same oral dose were performed after 1 month of continued therapy with L
      Dopa/carbidopa 125/12.5 mg three times daily. Patients were clinically evaluated
      by unified Parkinson's disease rating scale motor scores. There was a modest
      clinical improvement after 1 month of continuous L-Dopa treatment (motor scores,
      13.1 +/- 11.6 vs. 17.6 +/- 11.7; p < 0.01). Peak plasma L-Dopa levels and area
      under the curve did not differ significantly between the first-ever dose and
      after 1 month of continuous treatment (0.9 +/- 0.1 vs. 1.0 +/- 0.1 microg/mL and
      66.0 +/- 30.9 vs. 86.2 +/- 34.9 microg/mL, respectively; p < 0.1. There was also
      no change in time to peak levels between measurements. Results indicate that the
      first-ever dose of oral L-Dopa is well absorbed and that pharmacokinetic
      mechanisms such as reduced absorption of L-Dopa probably do not play a major role
      in the initial delay in clinical response to oral L-Dopa/carbidopa in patients
      with Parkinson's disease. The latter phenomena may be linked to central
      pharmacodynamic mechanisms.

PMID- 11307045
TI  - The effect of levodopa on vocal function in Parkinson's disease.
AB  - Phonatory and articulatory dysfunctions are frequent observations in Parkinson's
      disease. We have investigated, using acoustic measures, the effects of levodopa
      treatment on vocal function in 20 patients with Parkinson's disease before and
      after levodopa. These patients were also compared with a matched control group.
      The mean age was 63.5 +/- 9.66 years, Hoehn-Yahr stage was 2.38 +/- 0.45, and
      onset mean age was 56.5 +/- 10.36 years. Paired Wilcoxon tests were performed to
      compare measurements before and after levodopa. The acoustic analysis using
      Computerized Speech Lab and MultiDimensional Voice Program software programs (Kay
      Elemetrics, Lincoln Park, NJ, USA) showed that measurements of fundamental
      frequency (p < 0.017) were significantly increased after medication, whereas
      short-term frequency perturbation jitter (p < 0.033), soft phonation index (noise
      parameter) (p < 0.015 ), and frequency tremor intensity index (p < 0.018) were
      significantly decreased after medication. The objective measurements of acoustic
      analysis are useful in evaluating the dopaminergic pharmacologic response in
      Parkinson's disease. The improvement in fundamental frequency and other vocal
      parameters may be a result of decrease in laryngeal hypokinesia and rigidity.

PMID- 11307046
TI  - Gabapentin-induced hypersensitivity syndrome.
AB  - Hypersensitivity syndrome is a rare but potentially fatal reaction to some
      pharmacologic agents, including some antiepileptic drugs. Typically, the syndrome
      presents with fever, rash, tender lymphadenopathy, hepatitis, and eosinophilia.
      We report a novel case of clinical hypersensitivity syndrome secondary to
      gabapentin. A patient developed altered mental status, fever, diffuse macular
      rash, and an enlarged spleen. This constellation of symptoms and signs began 9
      days after gabapentin therapy was begun. Quick resolution was noted after
      gabapentin was discontinued. To our knowledge, there are no reports of
      hypersensitivity syndrome to gabapentin.

PMID- 11307047
TI  - Reversal of pathologic cardiac parameters after transition from clozapine to
      olanzapine treatment: a case report.
AB  - Antipsychotic medications have been associated with significant cardiovascular
      adverse effects and instances of sudden cardiac death. Recently, we started to
      evaluate cardiac parameters in medicated patients with schizophrenia using power
      spectrum analysis of heart rate variability. We present a case of a patient with
      long-standing schizophrenia who was treated with clozapine. His electrocardiogram
      revealed minor abnormalities, including a prolonged QT interval. Power spectrum
      analysis of heart rate variability demonstrated marked abnormalities in autonomic
      nervous system activity. Two years later, his treatment was switched to
      olanzapine. We reevaluated his cardiac parameters. Power spectrum analysis
      studies revealed that heart rate had significantly improved and that power
      spectrum cardiovascular parameters had returned to normal. Serial
      electrocardiograms revealed a minimally and asymptomatically prolonged QT
      interval. This case demonstrates the importance of screening electrocardiograms,
      even in healthy young patients. It also emphasizes how minor changes in
      electrocardiogram can be overlooked on standard electrocardiograms. Power
      spectrum analysis of heart rate variability is useful in this instance because it
      magnifies the trace and detects even minor disturbances. Care should be taken in
      prescribing antipsychotic drugs to patients who are prone to cardiovascular side
      effects, and alternatives to antipsychotics with prominent anticholinergic
      profile, in particular, should be sought.

PMID- 11307048
TI  - Topiramate in trigeminal neuralgia: a randomized, placebo-controlled multiple
      crossover pilot study.
AB  - We conducted a pilot study to evaluate the efficacy of topiramate in trigeminal
      neuralgia using a randomized, double-blind, placebo-controlled, two-period
      crossover design. Three patients were enrolled in and completed the study. All
      three patients responded to topiramate in this main study and entered a
      subsequent confirmatory study consisting of three topiramate-placebo crossovers.
      In the main study, topiramate reduced pain by 31%, 42%, and 64% in the three
      patients (p = 0.04). However, topiramate showed no effect in the confirmatory
      study. Given that trials of less common pain conditions are fraught with low
      patient recruitment rates, a multiple crossover design provides more information,
      which is important in conditions associated with considerable pain fluctuation.
      Larger trials are needed to more precisely estimate the effect of topiramate in
      trigeminal neuralgia.

PMID- 11307050
TI  - Low-dose clozapine for the treatment of Parkinson's disease in a patient with
      schizophrenia.
AB  - Clozapine is known to be beneficial for the treatment of dopamine agonist-induced
      psychotic states in patients with Parkinson's disease (PD). Many reports have
      suggested that it may also be efficacious for the treatment of parkinsonian
      tremor. We describe a patient with schizophrenia in whom early-onset PD appeared
      after treatment with antipsychotic drugs. When the parkinsonian symptoms proved
      resistant to anticholinergic agents, we introduced a trial with up to 50 mg
      clozapine daily, which yielded a prompt and dramatic response. Thereafter, the
      parkinsonian symptoms reappeared each time the patient discontinued clozapine and
      rapidly disappeared on its repeat initiation. There was also a marked improvement
      in his psychotic and depressive symptoms. This report suggests that some patients
      with concomitant schizophrenia and PD-a difficult treatment challenge-may benefit
      from clozapine treatment alone for both disorders.

PMID- 11307049
TI  - Possible oxcarbazepine interaction with cyclosporine serum levels: a single case
      study.
AB  - We studied the influence of an add-on medication with oxcarbazepine on the
      cyclosporine trough level in a kidney transplant recipient with pharmacoresistant
      epilepsy. Two weeks after the beginning of the trial we observed a decrease of
      the cyclosporine trough and the Na serum levels. Both could be corrected by a
      small-dose reduction of oxcarbazepine, an augmentation of the cyclosporine dosis,
      and oral sodium chloride substitution. After this episode the cyclosporine trough
      and the Na serum levels remained stable. Seizure frequency was reduced by 95%.
      The influence of oxcarbazepine on the cyclosporine serum level has to be studied
      carefully in other patients after transplantation before the use of oxcarbazepine
      can be recommended in patients with an immunosuppressive medication with
      cyclosporine. Our data suggest that oxcarbazepine may be an effective drug with
      tolerable side effects in this group of patients.

PMID- 11307051
TI  - Autopsy follow-up of a patient with schizophrenia and presumed idiopathic
      Parkinson's disease.

PMID- 11307052
TI  - Re: polyradiculoneuritis after botulinum toxin therapy for cervical dystonia.

PMID- 11307053
TI  - Valproate-related edema.

PMID- 11307054
TI  - Ocular manifestations of central nervous system lymphoma.
AB  - Primary intraocular lymphoma (PIOL) is a variant of primary central nervous
      system lymphoma in which lymphoma cells are initially present only in the eyes
      without evidence of disease in the brain or cerebrospinal fluid. Patients with
      PIOL are typically older adults who present with blurred vision and floaters. The
      ophthalmic examination characteristically shows a cellular infiltrate in the
      vitreous with or without the presence of subretinal infiltrates. Diagnostic
      evaluation for PIOL includes neuroimaging, cytologic examination of the
      cerebrospinal fluid, and a diagnostic vitrectomy with special handling of the
      vitreous specimen, if the former is nondiagnostic. Molecular and cytokine
      analyses are useful adjuncts to cytology for the diagnosis of PIOL. Recent
      molecular studies demonstrating viral DNA in the ocular lymphoma cells suggest a
      role for infectious agents in the pathogenesis of PIOL. To date, the best mode
      for treatment of PIOL or recurrent primary central nervous system lymphoma
      involving only the eyes remains undefined.

PMID- 11307055
TI  - Brain tumor animal models: importance and progress.
AB  - Recent experiments indicate that some of the genetic abnormalities found in human
      brain tumors can induce tumors in mice with similar histologic characteristics to
      their human counterparts. Such studies help unravel the biology of tumorigenesis
      and indicate that some of the mutations and alterations in gene expression found
      in human central nervous system tumors may actually contribute to the etiology of
      these diseases. In addition, these mouse-modeling experiments may identify
      essential targets for therapy and provide test animals for preclinical trials of
      mechanistically designed therapeutics.

PMID- 11307056
TI  - New advances in brain tumor imaging.
AB  - During the period of this review, there has been continued use and development of
      neuroimaging techniques in brain tumor diagnosis and management. Although no
      monumental developments or improvements in neuroimaging techniques or technology
      have occurred, important studies continue to be published showing the clinical
      impact and utility of various neuroimaging techniques to improve the care of
      patients with brain tumors. Several studies have shown the power of functional
      neuroimaging techniques with both magnetic resonance imaging (MRI) and positron
      emission tomography (PET) to map eloquent cortex and assist in the planning of
      surgical and radiation therapy. New nuclear imaging radiopharmaceuticals,
      including various PET ligands and single photon emission computed tomography
      (SPECT) agents, have also been developed and show their potential power in the
      evaluation of brain tumor patients. New MRI pulse sequences to improve image
      quality and shorten imaging time have also been developed. Several excellent
      reviews of the use of fluorodeoxyglucose (FDG)-PET and MRI techniques were also
      published. This article reviews the relevant and important neuroimaging
      literature related to brain tumor that was published during the defined time
      period of November 1, 1999 to October 31, 2000. Discussion is organized by
      modality, including nuclear imaging techniques (SPECT and PET) and MRI (pulse
      sequence development, contrast agent development, functional MRI developments,
      and general MRI-related information).

PMID- 11307057
TI  - Treatment controversies in medulloblastoma.
AB  - Medulloblastoma, the most common primary malignant brain tumor in children, is a
      radiosensitive and chemosensitive tumor. Nevertheless, medulloblastoma remains a
      management challenge for the clinical oncologist, because the optimal sequence
      and dosage for each treatment modality has not yet been defined. In addition,
      effective management strategies for medulloblastoma may result in profound
      neuroendocrine and neuropsychologic sequelae. In this article, we review the
      clinical and biologic prognostic factors for classifying medulloblastoma, current
      strategies for the management of this disease, and potential strategies to
      prevent or minimize long-term treatment sequelae.

PMID- 11307058
TI  - Brain and other central nervous system tumors: rates, trends, and epidemiology.
AB  - Reports that central nervous system (CNS) cancer rates are increasing have
      prompted debate on whether secular trends reflect environmental changes related
      to etiology or artifacts of case ascertainment. We present the most recent data
      from the National Cancer Institute's Surveillance, Epidemiology, and End Results
      program on incidence rates and trends of CNS malignancies, including primary CNS
      lymphomas, and on survival probability. We discuss the new 2000 standard for
      adjusting rates; underreporting of CNS tumor rates resulting from the exclusion
      of nonmalignancies in most cancer registries; and information on CNS tumor risk
      factors, including concerns related to nonionizing electromagnetic fields and
      wireless mobile telephones.

PMID- 11307060
TI  - Targeting growth factor receptors: integration of novel therapeutics in the
      management of head and neck cancer.
AB  - Tyrosine kinase (type 1) growth factor receptors include the erbB family. These
      cell surface receptors were discovered in the context of cellular transformation
      and have subsequently been found to be overexpressed in many types of human
      cancer. Cumulative evidence suggests that upregulation of the most well
      characterized receptor, erbB1, also known as the epidermal growth factor
      receptor, plays a significant role in the development and progression of head and
      neck squamous cell carcinoma. A variety of strategies have been developed that
      specifically target epidermal growth factor receptor, including monoclonal
      antibodies, ligand-linked immunotoxins, tyrosine kinase inhibitors, and antisense
      approaches. Epidermal growth factor receptor blockade in head and neck squamous
      cell carcinoma cell lines and preclinical animal models inhibits cell
      proliferation and tumor growth. Clinical trials are under way to test the safety
      and efficacy of many of these targeting strategies in head and neck squamous cell
      carcinoma patients. Encouraging preliminary results combining an epidermal growth
      factor receptor targeting approaches with chemotherapy or radiotherapy suggest
      that interference with this growth factor receptor may enhance antitumor efficacy
      of standard therapies. As erbB family member interactions and downstream
      signaling pathways are elucidated in head and neck squamous cell carcinoma,
      specific targeting strategies may become incorporated into standard treatment
      approaches.

PMID- 11307061
TI  - Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic
      characteristics and implications for management.
AB  - Squamous cell carcinoma of the head and neck has been strongly linked to chronic
      tobacco and alcohol abuse. However, we are increasingly recognizing subgroups of
      patients without traditional risk factors. Recent clinical and molecular
      investigations suggest that there are distinctive clinical entities, particularly
      affecting young patients with cancers of the oral tongue and oropharynx. We
      review data from clinical observations and current biologic inquiries and
      consider therapeutic implications for these important patient subgroups.

PMID- 11307062
TI  - Human papillomavirus-associated head and neck squamous cell carcinoma: mounting
      evidence for an etiologic role for human papillomavirus in a subset of head and
      neck cancers.
AB  - There is increasing molecular and epidemiologic evidence that human
      papillomavirus (HPV) is associated with a distinct subset of head and neck
      squamous cell carcinomas. The strength and consistency of HPV DNA presence in
      oropharyngeal cancers bolster the argument that this association is likely
      causal. HPV-positive tonsillar cancer in particular is emerging as a specific
      disease entity with distinct molecular, pathologic, and clinical characteristics.
      Recent data suggest that the incidence of tonsillar carcinoma in the United
      States is increasing, despite a decline in tobacco use, supporting the existence
      of other important risk factors such as HPV infection. Individuals with a history
      of an HPV-associated anogenital cancer and HIV-infected men are at increased risk
      for tonsillar carcinoma. This review focuses on the recent literature (since
      1998) investigating the relationship between HPV and head and neck cancer
      development, using the current paradigm for causal inference in epidemiologic
      research attributed to Sir A. Bradford Hill. Data examining the association of
      HPV with pathogenesis of head and neck squamous cell carcinoma before 1999 were
      previously reviewed in this journal.

PMID- 11307064
TI  - Testicular cancer.
AB  - A report of a 5-year survival rate of 39% for all patients with testis cancer in
      Kenya contrasts sharply with the 62% 5-year survival rate after tandem high-dose
      chemotherapy in first-line salvage of metastatic nonseminoma, and this figure
      provides a stark reminder of the differences in level of health care in the
      world. Nothing matches, however, the international significance of the success of
      Lance Armstrong in winning the Tour de France for the second time. It brings home
      the message of how complete the cure of this disease is and the need for more to
      be done to educate people about this success and encourage us to seek to discover
      the scientific basis for why this cancer is so different from all other cancers.
      The discovery that Lance Armstrong's brain metastases were totally necrotic at
      day 21 after the first treatment, taken with a report on the use of day 21
      computed tomograph response to predict outcome, reinforces that message. With a
      second report suggesting that there are regions of the world that may have
      escaped the environmental damage to fertility that is now increasingly accepted
      as the most significant risk factor for development of this disease, we also need
      to remember the importance of germ cells as a weather vane of the environment.
      The first breakthrough in identifying a specific genetic region on the X
      chromosome with susceptibility to germ cell cancer of the testis by its
      association with development of undescended testis was one of the scientific
      landmarks of this past year. Clinically, with such high cure rates after salvage
      treatments, most of the controversy focuses now on early management of this
      disease. Debate continues regarding the need for orchidectomy or node dissection
      before chemotherapy in patients with metastases. There is also considerable
      debate concerning the need for any adjuvant treatment in stage 1 disease, whether
      surgical, chemotherapeutic, or radiotherapeutic. With reviews on late events
      highlighting the possibility that cisplatin dosage may be critical in synergizing
      with etoposide in causing leukemia and late cardiovascular events and reports
      suggesting that circulating cisplatin can be detected in the plasma as long as 20
      years after treatment, the message of the year is clearly how to safely minimize
      the amount of treatment.

PMID- 11307065
TI  - Renal cell carcinoma.
AB  - Several renal cell carcinoma (RCC) prognostic factors show promise, including K1
      67, p53/mdm-2, and vascular endothelial growth factor. The combination of
      increased incidence of RCC and diagnosis during earlier stages has generated
      interest in local therapeutic options. Nephron-sparing surgery and laparoscopic
      nephrectomy continue to gain support and may become the standard of care in
      select patients. Standard therapy for metastatic disease continues to be cytokine
      based therapy with little benefit gained from adding granulocyte-macrophage
      colony-stimulating factor, retinoic acid, or adoptive immunotherapy. The addition
      of chemotherapy, such as capecitabine, floxuridine, and vinblastine, may increase
      the effectiveness of immunotherapy; nonmyeloablative stem cell transplantation
      has shown early promise in metastatic disease.

PMID- 11307066
TI  - An update on prostate cancer.
AB  - Consideration of the number of prostate biopsy samples found to be positive for
      cancer may add clinically useful information to T stage, Gleason score, and
      prostate-specific antigen level in predicting outcome after radical
      prostatectomy. Higher radiation doses and neoadjuvant hormone therapy has been
      applied successfully to patients with higher risk disease. Brachytherapy has
      emerged as a modality for localized prostate cancer with outcomes and toxicity
      being further defined. Efforts to measure and improve quality of life are an
      important part of prostate cancer research. Standard management of metastatic
      disease remains androgen ablation, with long-term side effects being recognized.
      Newer hormonal and chemotherapeutic agents are being explored for patients with
      metastatic disease.

PMID- 11307067
TI  - Pediatric genitourinary tumors.
AB  - Each year advances are made in the evaluation and management of genitourinary
      tumors in children. There is increased understanding of molecular and genetic
      processes in tumorigenesis. In addition, knowledge concerning the current
      treatment modalities is increasing, thus allowing us to tailor treatments in
      order to decrease long-term complications. In this article, we review this past
      year's literature regarding pediatric genitourinary tumors with emphasis on Wilms
      tumor, rhabdomyosarcoma, and testicular tumors.

PMID- 11307068
TI  - Obstructive sleep apnea: A sleep disorder with major effects on health.

PMID- 11307069
TI  - Rotator cuff repairs in patients 62 years of age or older.
AB  - We retrospectively reviewed 105 consecutive patients aged 62 years and older who
      had undergone a repair of a rotator cuff tear to evaluate the efficacy of this
      surgery in patients in this age range. Six patients died, and 7 had less than 2
      years of follow-up or were incapable of returning for examination. Ninety-two
      patients with 97 rotator cuff tears were re-examined. The average preoperative
      UCLA (University of California, Los Angeles) score was 12.9 (range 8 to 20), and
      the average postoperative score was 32.4 (range 12 to 35). Five patients (5%) had
      failure of the repair, accounting for the poor results. Severe complications
      included infection (1 patient) and brachial plexus stretch injury (1 patient).
      Four additional patients sustained minor complications, for an overall rate of
      6%. Overall, 87% of patients had good or excellent results. Eight additional
      patients, while satisfied, were classified as fair. Of the 5 failures, 3 were
      revised to a satisfactory result. Thus 90 of the 92 patients in the study were
      satisfied with the result of the surgery at final follow-up. Rotator cuff repair
      in patients 62 years and older results in increased function, decreased pain, and
      satisfactory results.

PMID- 11307070
TI  - The natural course of atraumatic shoulder instability.
AB  - Over the years, we have observed a shifting among loose shoulder, voluntary
      dislocation, habitual dislocation, and sustained subluxation, leading us to the
      conclusion that they are all varieties of the same condition: atraumatic shoulder
      instability. For this study, we followed the natural course of atraumatic
      shoulder instability in 341 patients (573 shoulders) for 3 years or more. There
      were 467 cases of loose shoulder, 49 cases of voluntary dislocation, 56 cases of
      habitual dislocation, and 1 case of sustained subluxation. The average follow-up
      period was 4 years and 6 months. Spontaneous recovery occurred in 50 cases. The
      average age of patients at the onset of atraumatic shoulder instability who
      exhibited a change in instability was 14.6 years. The average age of patients at
      the onset of atraumatic shoulder instability who exhibited no change in shoulder
      instability was 19.4 years. There was a significant difference of P < .01 in the
      age of onset between these two groups. The incidence of spontaneous recovery in
      the group that discontinued overhead sports was 8.7 times greater than in the
      group that continued to play overhead sports. The incidence of spontaneous
      recovery in the group that discontinued non-overhead sports was only 1.4 times
      greater than in the group that continued to play non-overhead sports. However, no
      instance of spontaneous recovery was observed among patients who changed from
      playing non-overhead sports to playing overhead sports. The spontaneous recovery
      of atraumatic shoulder instability encountered in this study shows that it is
      best to place priority on observing the course of atraumatic shoulder instability
      for several years and to avoid performing unnecessary surgery.

PMID- 11307071
TI  - Comparison of an arthroscopic and an open procedure for posttraumatic instability
      of the shoulder: a prospective, randomized multicenter study.
AB  - From 1993 through 1996, a multicenter study was conducted on the surgical
      treatment of patients with posttraumatic recurrent anterior shoulder
      dislocations. Fifty-six patients (40 men, 16 women; mean age 26 years [range 18
      51 years]), were evaluated with shoulder arthroscopy. If a Bankart lesion was
      present, the patients were randomly allocated to either an arthroscopic
      reconstruction with the use of biodegradable tacks or an open reconstruction with
      suture anchors. The postoperative rehabilitation protocol for the two groups was
      identical. In all patients, the range of shoulder motion, stability, and the
      Constant and Rowe scores were evaluated at 3, 12, and 24 months postoperatively.
      Thirty patients were surgically treated with the arthroscopic technique and 26
      patients with the open technique. In the arthroscopic group, there were
      recurrences in 7 (23%) of 30 patients at a mean of 13 months (range 5 to 21
      months) after surgery. All patients with stable shoulders had a negative
      apprehension test result. In the open group, there were recurrences in 3 (12%) of
      26 patients at a mean of 10 months (range 2 to 23 months) after surgery (P = not
      significant). In the arthroscopic group, 2 patients had new traumatic
      redislocations, whereas 1 patient redislocated during an epileptic seizure. In
      the open group, 1 traumatic redislocation occurred. The 2-year results in this
      study demonstrate a large number of redislocations after reconstruction, even in
      the open surgery group. Patient noncompliance with the rehabilitation protocol
      and predisposing disease may partially explain these results. A tendency was seen
      toward more redislocations in the arthroscopic group, which emphasizes the
      importance of correct patient selection and careful surgical technique in the
      difficult surgical procedure.

PMID- 11307072
TI  - Laminated tears of the human rotator cuff: a histologic and immunochemical study.
AB  - Laminated tears of the rotator cuff are often lined by a cellular layer that has
      an appearance suggestive of synovium. This study demonstrates, by histologic and
      immunohistochemical means, that the lining cells are synovial. It remains unclear
      whether these cells arise by synovial extension from the joint or bursa, or by
      metaplasia in the presence of synovial fluid, and this has implications for
      surgical repair of laminated cuff defects. We suggest that these defects be
      curetted, to remove at least some of this synovial lining, before suture repair.

PMID- 11307073
TI  - In vivo characterization of glenoid with use of computed tomography.
AB  - Improvement in the treatment of the shoulder could be achieved by accurately
      describing the pathologic characteristics of the joint. The goal of this study
      was to characterize, in vivo, glenoids with 3 different diagnoses by using
      computed tomography (CT): rotator cuff pathology with a limited rupture and
      without bony changes (group A, n = 15), primary osteoarthritis (group B, n = 13),
      and rheumatoid arthritis (group C, n = 4). The bone density distribution was
      assessed by means of the CT value expressed in Hounsfield units. The version
      angle was also measured. The examination of the CT value showed different
      distributions according to the pathology. In group A, the cancellous bone
      presented a central area with a relatively homogeneous and low density. In group
      B, the reinforcement of the density along with the posterior region seemed to be
      correlated with the retroversion angle. In the rheumatoid arthritis group, the
      main characteristic was the loss of the subchondral bone margin. The cartography
      of the CT value was not reproducible among the 4 cases examined. These in vivo
      descriptions provide guidelines for the surgeon before total shoulder
      arthroplasty, helping preoperative planning as well as simulation of
      implantation.

PMID- 11307074
TI  - Fibrous connection to bone after immediate repair of the canine infraspinatus:
      the most effective bony surface for tendon attachment.
AB  - The purpose of this histologic study was to identify the most effective bony
      surface for fibrous connection to bone after immediate repair of the canine
      infraspinatus. Light microscopic views were used to evaluate collagen fiber
      development. The left infraspinatus tendon of 15 dogs was transected and repaired
      to 3 different bone surfaces: a tendon end adjacent to the tendon insertion
      (group 1, n = 5), a calcified fibrocartilage layer (group 2, n = 5), and a
      cancellous surface (group 3, n = 5). Tendon repair to distal tendon ends restored
      the 4-layered enthesis in the healing period, whereas tendon repair to the
      calcified fibrocartilage layer considerably delayed fiber development into bone.
      Fiber connection to cancellous surface developed according to the remodeling of
      trabecular bone. Secure fiber connection into the thickened trabecular bone
      developed by 16 postoperative weeks. On the basis of these results, in clinical
      settings, ruptured tendon ends should be attached to the remaining distal tendon
      end or to a cancellous surface; they should not be attached to a calcified
      fibrocartilage layer.

PMID- 11307075
TI  - Sex-specific differences of subacromial space width during abduction, with and
      without muscular activity, and correlation with anthropometric variables.
AB  - The objectives of this study were to determine sex-specific differences of the
      subacromial space width during active and passive arm abduction and to analyze
      the correlation of this space with general and regional anthropometric variables.
      Fourteen healthy subjects (7 men, 7 women) were examined with an open magnetic
      resonance system at 30 degrees and 90 degrees of abduction (with and without
      muscle activity). After 3-dimensional reconstruction, the minimal acromiohumeral
      distance, the glenoid size, and the humeral head radius were determined. At 30
      degrees of abduction, a significant difference of the acromiohumeral distance was
      observed between men (8.18 +/- 1.0 mm) and women (6.98 +/- 0.75 mm) (P < .05),
      but not at 90 degrees (6.7 +/- 2.0 mm versus 5.9 +/- 1.0 mm) or under muscle
      activity (4.9 +/- 2.4 mm versus 3.5 +/- 2.1 mm). Significant correlations between
      the acromiohumeral distance and anthropometric variables were found at 30 degrees
      of abduction (r = 0.48 to 0.72), but not at 90 degrees, with or without muscle
      activity (r = 0.21 to 0.55). The results demonstrate that at physical rest, the
      subacromial space width is dependent on sex, but the interindividual variability
      increases substantially during abduction and under muscle activity.

PMID- 11307076
TI  - The bicipital groove as a landmark for orientation of the humeral prosthesis in
      cases of fracture.
AB  - We studied 45 dry cadaveric humeri to determine whether the bicipital groove of
      the humerus can be used as a landmark for a proper, individualized orientation of
      a humeral prosthesis, especially in the case of a fracture. We performed 3
      computed tomography sections (at a level just below the lower portion of the
      head, at the middle of the humeral head, and at a distance 5 cm below the first
      section), and we used special software for 3-dimensional image processing. To
      reproduce the individual posterior version of the head, when a humeral prosthesis
      is implanted for fracture, the lateral fin of the prosthesis should be a mean
      distance 5.2 +/- 2.6 mm (-1.5 to 10.7 mm) from the posterior edge of the
      bicipital groove. If the lateral fin of the humeral prosthesis seats just behind
      the posterior edge of the bicipital groove, a difference of -6.3 degrees to 41.7
      degrees from the normal posterior version occurs. A new, simple methodology for
      an individualized posterior version of a humeral prosthesis in cases of fracture
      is proposed. We applied this in 6 consecutive patients with fracture of the
      humeral head that required hemiarthroplasty.

PMID- 11307077
TI  - Radiologic, mechanical, and histologic evaluation of 2 glenoid prosthesis designs
      in a canine model.
AB  - Aseptic loosening of glenoid components is a common problem associated with total
      shoulder arthroplasty. A new glenoid design aimed at improving fixation outcomes
      was compared with conventional keeled glenoids in weight-bearing canine
      shoulders. Radiographic, histologic, and mechanical tests were performed at 3
      postoperative intervals (0, 3, and 6 months). The uncemented pegged glenoid
      achieved bone ingrowth around the peg flanges in each case. This result was
      confirmed histologically and radiographically. Mechanical results indicated that
      mean fixation strength increases significantly between 0 and 3 months after
      surgery and remains strong through 6 months. In contrast, conventional keeled
      glenoids were found to have partial or complete radiolucent lines around the keel
      in each instance, and mechanical testing demonstrated that mean fixation strength
      weakens significantly between 0 and 3 months after surgery and remains weak
      through 6 months. These results show that stem design changes can improve implant
      fixation. A cementless fluted peg stem was superior to a conventional cemented
      keel design in achieving osseous integration and fixation in a weight-bearing
      animal model.

PMID- 11307078
TI  - The association between frozen shoulder and Dupuytren's disease.
AB  - Fifty-eight patients with the diagnosis of primary frozen shoulder were
      independently examined by 3 surgeons for evidence of Dupuytren's disease. The
      disease was found in 52% (30/58) of the patients reviewed. These figures were
      compared with previously reported figures for a population of similar age. This
      showed that Dupuytren's disease is 8.27 (95% CI, 6.25-11.2) times more common in
      patients with frozen shoulder than in the general population; the difference
      between the two was highly statistically significant (P < .001, chi(2) test). We
      discuss the literature on the association between frozen shoulder and Dupuytren's
      disease and the implications of such a high proportion of patients sharing these
      two conditions.

PMID- 11307079
TI  - Ulnar collateral ligament reconstruction in athletes: muscle-splitting approach
      without transposition of the ulnar nerve.
AB  - Eighty-three athletes with medial elbow instability underwent reconstruction of
      the anterior band of the ulnar collateral ligament with a muscle-splitting
      approach without transposition of the ulnar nerve. The purposes of this study
      were to describe postoperative neurologic outcomes in all 83 athletes and to
      describe the 2-year follow-up in 33 athletes. Postoperatively, 5% of this group
      had transient ulnar nerve symptoms, all of which resolved with nonoperative
      management. There were no reoperations for nerve dysfunction and no permanent
      nerve problems. At 2- to 4-year follow-ups, 93% of the highly competitive
      athletes who had not had a prior surgical procedure had an excellent result. All
      athletes, regardless of whether they had a prior procedure, were able to return
      to their sport. These surgical modifications to the ulnar collateral ligament
      reconstruction yielded a decreased postoperative complication rate and improved
      outcomes compared with the results of prior procedures.

PMID- 11307080
TI  - Bony changes at the lateral epicondyle of possible significance in tennis elbow
      syndrome.
AB  - Examination of a large number (1232) of elbows from skeletal specimens revealed
      that 16% displayed a characteristic pattern of bone formation exactly underlying
      the area of exquisite point tenderness at the lateral humeral epicondyle found in
      clinical cases of tennis elbow. These changes are usually not seen on standard
      roentgenograms and can be missed, even at the time of surgery, because this area
      is not commonly exposed in standard tennis elbow approaches. In a group of
      clinical cases of tennis elbow (20 patients), similar bony changes could be
      demonstrated in the majority (60%) of patients with chronic tennis elbow symptoms
      by the use of specialized x-ray techniques-most notably, coronal reconstructions
      with computed axial tomography. Ten cadaver specimens were also dissected to
      delineate the muscular and capsulotendinous insertions in this area. We call
      attention to these bony changes in the supposition that they may be involved in
      the development and persistence of symptoms in tennis elbow.

PMID- 11307081
TI  - Early, wide excision of heterotopic ossification in the medial elbow.
AB  - To prevent the occurrence of secondary contracture during maturation of
      heterotopic ossification of the elbow, early, wide excision of heterotopic
      ossification was performed on 9 consecutive patients with a stiff elbow caused by
      the mass. The average duration between initial injury and operation was 7.7
      months. The thick, elastic mass on the posterior oblique ligament of the medial
      collateral ligament, which included mature and immature heterotopic ossification,
      was resected widely with the posterior oblique ligament, the posteromedial joint
      capsule, and the surrounding scar tissue. After an average follow-up of 52.0
      months, the total arc of motion improved from a preoperative mean of 37.3 degrees
      to a postoperative mean of 112.8 degrees. No patient complained of instability or
      pain on movement. Despite recurrence of spotty heterotopic ossification at the
      medial elbow in 5 cases, at final follow-up, a sufficient range of motion was
      obtained in all patients.

PMID- 11307082
TI  - Which morphologies of synovial folds result from degeneration and/or aging of the
      radiohumeral joint: an anatomic study with cadavers and embryos.
AB  - The synovial folds of the radiohumeral joints in cadaveric elbows from 179
      elderly subjects and 40 embryos were investigated macroscopically and
      histologically to determine any morphologic changes caused by aging or
      degeneration. The anterior and posterior folds found in the elderly population
      shared characteristics of folds seen in embryos, with some modifications, and
      were thought to originate from the primitive septum. Proportionally, the length,
      width, and thickness of these folds were consistent between adults and embryos.
      However, the embryonic folds showed a homogenous morphology. In contrast, in the
      adult the anterior fold was characterized by a shorter and narrower villous
      pattern, and the posterior fold tended to be wider. Lateral extension of the
      anterior or posterior folds was also observed. Moreover, the lateral fold, never
      seen in embryos, was present and characterized by a hard plicate pattern in the
      adult. These derived or specific morphologies in adults probably result from
      alterations in the movement of the radial head caused by aging.

PMID- 11307083
TI  - An atypical appearance of a posterior dislocation of the shoulder with a fracture
      of the proximal humerus.

PMID- 11307084
TI  - Two cases of synovial chondromatosis of the subacromial bursa.

PMID- 11307085
TI  - Surgical treatment of a desmoid tumor from the serratus anterior in the
      subscapular region with use of a scapula-splitting posterior approach.

PMID- 11307086
TI  - Cubital tunnel syndrome caused by tumoral deposition of calcium pyrophosphate
      dihydrate crystals: a case report.

PMID- 11307087
TI  - Rotational dissociation of glenoid components in a total shoulder prosthesis: an
      indication that sagittal torque forces may be important in glenoid component
      design.

PMID- 11307089
TI  - Fusion of unstable os acromiale.

PMID- 11307091
TI  - Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and
      prognostic indicators.
AB  - This large-volume, single-institution review examines factors influencing long
      term survival after resection in patients with adenocarcinoma of the head, neck,
      uncinate process, body, or tail of the pancreas. Between January 1984 and July
      1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent
      surgical resection. A retrospective analysis of a prospectively collected
      database was performed. Both univariate and multivariate models were used to
      determine the factors influencing survival. Of the 616 patients, 526 (85%)
      underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or
      uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for
      adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy
      for adenocarcinoma extensively involving the gland. The mean age of the patients
      was 64.3 years, with 54% being male and 91% being white. The overall
      perioperative mortality rate was 2.3%, whereas the incidence of postoperative
      complications was 30%. The median postoperative length of stay was 11 days. The
      mean tumor diameter was 3.2 cm, with 72% of patients having positive lymph nodes,
      30% having positive resection margins, and 36% having poorly differentiated
      tumors. Patients undergoing distal pancreatectomy for left-sided lesions had
      larger tumors (4.7 vs. 3.1 cm, P < 0.0001), but fewer node-positive resections
      (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P <
      0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided
      lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5
      years, with a median survival of 17 months. For right-sided lesions the 1- and 5
      year survival rates were 64% and 17%, respectively, compared to 50% and 15% for
      left-sided lesions. Factors shown to have favorable independent prognostic
      significance by multivariate analysis were negative resection margins (hazard
      ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor
      diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated
      blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02),
      well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005),
      and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P < 0.0001).
      Tumor location in head, neck, or uncinate process approached significance in the
      final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic
      resection remains the only hope for long-term survival in patients with
      adenocarcinoma of the pancreas. Completeness of resection and tumor
      characteristics including tumor size and degree of differentiation are important
      independent prognostic indicators. Adjuvant chemoradiation is a strong predictor
      of outcome and likely decreases the independent significance of tumor location
      and nodal status.

PMID- 11307092
TI  - Effective treatment of pancreatic tumors with two multimutated herpes simplex
      oncolytic viruses.
AB  - Pancreatic cancer is an aggressive, rapidly fatal disease against which current
      nonsurgical therapy has minimal impact. This study evaluates the efficacy of two
      novel, replication-competent, multimutated herpes viruses (G207 and NV1020) in an
      experimental model of pancreatic cancer. Four human pancreatic carcinoma cell
      lines were exposed to G207 or NV1020, and cell survival and viral progeny
      production were determined. Flank tumors in athymic mice were subjected to single
      or multiple injections of 1 x 10(7) G207 or NV1020, and tumor volume was
      evaluated over time. For all of the cell lines, G207 and NV1020 produced
      infection, viral replication, and cell lysis (P < 0.05). NV1020 resulted in a
      higher production of viral progeny compared to G207. The efficacy of viral tumor
      cell kill was greatest in those cells with the shortest in vitro doubling time.
      For flank tumors derived from hs766t, single or multiple injections of both
      viruses were equally effective and significantly reduced flank tumor burden (P <
      0.05). Complete hs766t flank tumor eradication was achieved in 25% (5 of 20) of
      animals treated with G207 and 40% (8 of 20) of animals treated with NV1020. In
      vivo efficacy correlated with in vivo tumor doubling time. There were no adverse
      effects related to viral administration observed in any animal. NV1020 and G207
      effectively infect and kill human pancreatic cancer cells in vitro and in vivo.
      Given the lack of effective nonoperative treatments for pancreatic cancer,
      oncolytic herpes viruses should be considered for clinical evaluation.

PMID- 11307093
TI  - Transjugular intrahepatic portosystemic shunt vs. small-diameter prosthetic H
      graft portacaval shunt: extended follow-up of an expanded randomized prospective
      trial.
AB  - We report herein the results of extended follow-up of an expanded randomized
      clinical trial comparing transjugular intrahepatic portosystemic shunt (TIPS) to
      8 mm prosthetic H-graft portacaval shunt as definitive treatment for variceal
      bleeding due to portal hypertension. Beginning in 1993, through this trial, both
      shunts were undertaken as definitive therapy, never as a "bridge to
      transplantation." All patients had bleeding esophageal/gastric varices and failed
      or could not undergo sclerotherapy/banding. Patients were excluded from
      randomization if the portal vein was occluded or if survival was hopeless.
      Failure of shunting was defined as inability to shunt, irreversible shunt
      occlusion, major variceal rehemorrhage, hepatic transplantation, or death. Median
      follow-up after each shunt was 4 years; minimum follow-up was 1 year. Patients
      undergoing placement of either shunt were very similar in terms of age, sex,
      cause of cirrhosis, Child's class, and circumstances of shunting. Both shunts
      provided partial portal decompression, although the portal vein-inferior vena
      cava pressure gradient was lower after H-graft portacaval shunt (P < 0.01). TIPS
      could not be placed in two patients. Shunt stenosis/occlusion was more frequent
      after TIPS. After TIPS, 42 patients failed (64%), whereas after H-graft
      portacaval shunt 23 failed (35%) (P < 0.01). Major variceal rehemorrhage, hepatic
      transplantation, and late death were significantly more frequent after TIPS (P <
      0.01). Both TIPS and H-graft portacaval shunt achieve partial portal
      decompression. TIPS requires more interventions and leads to more major
      rehemorrhage, irreversible occlusion, transplantation, and death. Despite
      vigilance in monitoring shunt patency, TIPS provides less optimal outcomes than H
      graft portacaval shunt for patients with portal hypertension and variceal
      bleeding.

PMID- 11307094
TI  - Ten and more years after vertical banded gastroplasty as primary operation for
      morbid obesity.
AB  - Long-term follow-up (>10 years) after vertical banded gastroplasty (VBG) is
      almost nonexistent. The aim of this study was to determine long-term outcome
      after VBG in a group of 71 patients studied prospectively. Seventy-one
      consecutive patients with morbid obesity (54 women and 17 men; mean age 40 years
      [range 22 to 71 years]) underwent VBG from 1985 to 1989 and were followed
      prospectively. Follow-up was obtained in 70 (99%) of the 71 patients. Weight
      (mean +/- standard error of the mean) preoperatively was 138 +/- 3 kg and
      decreased to 108 +/- 2 kg 10 or more years postoperatively. Body mass index
      decreased from 49 +/-1 to 39 +/- 1. Only 14 (20%) of 70 patients lost and
      maintained the loss of at least half of their excess body weight with the VBG
      anatomy. Vomiting one or more times per week continues to occur in 21% and
      heartburn in 16%. Fourteen patients have undergone conversion from VBG to Roux-en
      Y gastric bypass (11 patients) or other procedures (3 patients) because of a
      combination of inadequate weight loss in 13 patients, gastroesophageal reflux in
      five, and frequent vomiting in four. Only 26% of patients after VBG have
      maintained a weight loss of at least 50% of their excess body weight; 17%
      underwent bariatric reoperation with good results. Thus VBG is not an effective,
      durable bariatric operation.

PMID- 11307095
TI  - Comparison of ceftibuten vs. amoxicillin/clavulanic acid as antibiotic
      prophylaxis in cholecystectomy and/or biliary tract surgery.
AB  - A randomized, comparative, prospective clinical trial was carried out at a
      tertiary care center to compare the efficacy of two antibiotic regimens in the
      prophylaxis of postoperative infection in patients undergoing biliary tract
      surgery. One hundred patients undergoing cholecystectomy or biliary tract
      exploration were randomly allocated to one of the following antibiotic regimens:
      the standard regimen of three doses of amoxicillin/clavulanic acid (1000/200 mg)
      given by intravenous infusion, or a single dose of ceftibuten (400 mg) given
      orally. Patients were monitored during their stay in the hospital and over a 2
      week period as outpatients. Fifty adult patients were included in each group.
      Mean age was 49 years, and sex distribution was 82 women and 18 men. The groups
      were comparable in terms of demographic characteristics and comorbidity. There
      were no cases of postoperative infection in the ceftibuten group, but five cases
      of infection occurred in the amoxicillin/clavulanic acid group (P < 0.05). No
      adverse effects were observed with either antibiotic. The treatment cost per
      patient was significantly lower for ceftibuten. The results indicate that
      ceftibuten is well tolerated and more effective than amoxicillin/clavulanic acid
      for prophylaxis following gallbladder and biliary tract surgery. In addition,
      ceftibuten has the advantage of being more cost-effective and easier to
      administer than amoxicillin/clavulanic acid so it could be considered as an
      alternative for antibiotic prophylaxis in these types of surgical procedures.

PMID- 11307096
TI  - Hemangioma of the spleen: presentation, diagnosis, and management.
AB  - Splenic hemangioma is a rare disorder but remains the most common benign neoplasm
      of the spleen. It often has a latent clinical picture; however, spontaneous
      rupture has been reported to occur in as many as 25% of this patient population.1
      Treatment most often consists of splenectomy. This report reviews an 8-year
      experience with splenic hemangioma at Mayo Clinic. Thirty-two patients were
      identified with SH during the 8-year study period. The average age was 63 years
      (range 23 to 94 years) with 17 women and 15 men. Six patients presented with
      symptoms potentially related to the SH. The remainder (80%) were asymptomatic,
      and the SH was discovered incidentally during evaluation for other disorders. A
      mass or palpable spleen was appreciated in only four patients (12.5%). SHs ranged
      in size from 0.3 to 7 cm maximum diameter. A diagnosis of SH was made in 11
      patients based on the findings of a splenic mass on computed tomography or
      ultrasound. Each of these SHs was < or =4 cm. Three of the 11 patients had
      multiple SHs. All 11 patients were managed successfully with observation. All but
      one of the patients remains asymptomatic, and no complications have developed
      during follow-up (range 0.6 to 7 years, mean 2.9 years). The diagnosis of splenic
      hemangioma was made at the time of surgery in the remaining 21 patients (65%).
      Splenectomy was performed for suspicion of primary or secondary splenic
      pathology. There were no instances of spontaneous rupture of the SH. Small
      splenic lesions, which meet the radiologic criteria for hemangiomas, may be
      safely observed.

PMID- 11307097
TI  - Matrix metalloproteinase inhibition improves survival in an orthotopic model of
      human pancreatic cancer.
AB  - Matrix metalloproteinases (MMPs) have been implicated in the growth and
      invasiveness of primary and metastatic tumors. Hypothesizing that MMP inhibition
      would slow cancer growth, the MMP inhibitor BB-94 (batimistat) was evaluated in
      an orthotopic animal model of human pancreatic carcinoma. Ten million human
      pancreatic cancer cells were surgically implanted into the pancreata of 30
      athymic nu/nu mice. Intraperitoneal administration of 30 mg/kg BB-94 or vehicle
      control began 7 days after tumor implantation (13 mice with confirmed
      implantations in each group) and continued daily for 21 days, and then three
      times weekly until death or sacrifice at day 70. Representative tumors harvested
      from mice in each group were analyzed for presence and activity of MMP-2 and MMP
      9. Animal weights were significantly higher in the BB-94-treated group at
      sacrifice (mean 58.4 +/- 7.9 g vs. 39.8 +/- 6.2 g; P < 0.05, Student's t test).
      The likelihood of survival to 70 days was significantly higher in the treated
      group (4 of 13 vs. 0 of 13, P < 0.05, Z-test for end points) than in the control
      group as was overall survival (P = 0.03, Wilcoxon test). Nine mice in the control
      group developed metastases to the liver, peritoneum, abdominal wall, or local
      lymph nodes, whereas only two mice in the BB-94 group had evidence of metastatic
      disease (P < 0.02, Fisher's exact test), in both instances confined to the
      abdominal wall. Tumors from treated mice manifested lower MMP activity than those
      from control animals. These reports support the use of MMP inhibitors alone or as
      an adjunct in the treatment of pancreatic cancer.

PMID- 11307098
TI  - Development of an in vivo tumor-mimic model for learning radiofrequency ablation.
AB  - Radiofrequency ablation requires accurate probe placement using ultrasound
      guidance. The purpose of this study was to develop an in vivo tumor-mimic model
      for learning open and laparoscopic radiofrequency ablation. Tumor-mimics were
      created in ex vivo porcine livers by injecting a mixture of 3% agarose, 3%
      cellulose, 7% glycerol, and 0.05% methylene blue, which formed 1 cm hyperechoic,
      discrete lesions on ultrasound. Open and laparoscopic (using a box-trainer)
      ablation techniques were practiced. In vivo experiments were then conducted in 10
      pigs. Three tumor-mimics were created in each animal using a laparoscopic
      approach. Lesions were characterized sonographically, ablated using an open (n =
      5) or laparoscopic (n = 5) approach, and examined pathologically. An ablation in
      normal liver tissue was performed as a control. Tissue impedance was recorded.
      Target creation took 81 minutes per animal and 96% of injections were successful.
      Tissue impedance (48.8 +/- 5.8 vs. 49.6 +/- 5.4) and ablation size (25.1 +/- 3.4
      vs. 24.3 +/- 5.1) were not significantly different for controls (n = 8) and tumor
      mimics (n = 26), respectively. One animal died of a pulmonary embolism following
      injection of agarose into a hepatic vein. The agarose-based tissue-mimic creates
      realistic sonographic targets for learning ultrasound-guided open and
      laparoscopic radiofrequency ablation in an in vivo model.

PMID- 11307099
TI  - Achalasia developing years after surgery for reflux disease: case reports,
      laparoscopic treatment, and review of achalasia syndromes following antireflux
      surgery.
AB  - Two case reports demonstrate the paradoxical occurrence of achalasia many years
      after the successful surgical treatment of gastroesophageal reflux disease
      (GERD). These patients had remedial surgery laparoscopically. The three types of
      achalasia syndromes that can follow antireflux surgery are discussed. In type 1,
      primary achalasia is misdiagnosed as GERD and inappropriate antireflux surgery
      causes worsening dysphagia immediately after surgery without any symptom-free
      interval. In type 2, secondary iatrogenic achalasia is seen early after
      antireflux surgery and is characterized by the presence of stenosis and scar
      formation at the site of the fundic wrap. Although the motility studies resemble
      achalasia, the repair needs only to be taken down and refashioned when there is
      no response to balloon dilatation. In type 3, illustrated by the case reports,
      primary achalasia follows antireflux surgery after a significant symptom-free
      interval. There is complete absence of any stenosis or fibrosis of the esophagus
      and periesophageal tissues at remedial surgery. Moreover, surgical treatment of
      this condition needs to include esophageal myotomy.

PMID- 11307100
TI  - Functional results after laparoscopic rectopexy for rectal prolapse.
AB  - We investigated the functional results after laparoscopic rectopexy for rectal
      prolapse in 29 patients at least 12 months postoperatively. Twenty patients were
      evaluated completely pre- and postoperatively (median 22 months postoperatively,
      range 12 to 54 months). Six patients were interviewed by telephone, two patients
      were lost to follow-up, and one patient died of causes unrelated to rectal
      prolapse. Patients underwent a proctologic examination, anoscopy, rigid
      sigmoidoscopy, fluoroscopic defecography, and anorectal manometry pre- and
      postoperatively, and an additional standardized interview postoperatively.
      Anorectal manometry showed a significant increase in maximum anal resting and
      squeeze pressures postoperatively (resting pressure 72 +/- 8 vs. 95 +/- 13 mm Hg,
      pre- vs. postoperatively; P = 0.046; squeeze pressure 105 +/- 17 vs. 142 +/- 19
      mm Hg, pre- vs. postoperatively; P = 0.035), and continence improved
      postoperatively (Wexner incontinence score 6.0 +/- 1.0 vs. 3.9 +/- 0.8 pre- vs.
      postoperatively, P = 0.02). Twenty (77%) of 26 patients were satisfied with the
      operative result, but functional morbidity was observed in four patients, with
      two patients complaining of severe evacuation problems. Rectal prolapse recurred
      in one patient 42 months postoperatively (recurrence rate 1 [3.8%] of 26
      patients). Functional results were very similar to those obtained after open
      rectopexy, with symptoms of prolapse and incontinence improved in the great
      majority of patients.

PMID- 11307102
TI  - Caring for hemodialysis patients in Saudi Arabia. Past, present and future.
AB  - There are currently 5706 patients receiving hemodialysis therapy in the Kingdom
      of Saudi Arabia - a 15 fold increase when compared to 1983. The annual increase
      in the number of patients on dialysis for 1999 is 696 (10 fold increase when
      compared to 1983). Besides the massive increase in the number of patients in the
      last 20 years, we have noticed a marked increase in the mean age of patients
      (51.3 years in 1999 as compared to 37.9 years in the early 80s). Diabetes
      mellitus which was an insignificant contributory etiology (4%) in the early 80s
      is now a major cause (16-25%). Similarly mortality has increased from 4% annually
      to 11-14% annually. This is largely due to increasing age and prevalence of
      diabetes mellitus. Within the expired cohort the mean age was 62.3 years compared
      to 51.3 years of the total dialysis population, and diabetes mellitus was present
      in 60.5% in those who expired. Moreover, ischemic heart disease was diagnosed in
      50% before death. Tuberculosis and Hepatitis C virus incidences, however, have
      not improved over the years but the degree of rehabilitation has, largely due to
      better hemoglobin level and due to the technological advances in dialysis
      delivery. This article describes these changes, their causes and implications.

PMID- 11307101
TI  - Symptomatic gallstones in patients with spinal cord injury.
AB  - Patients with spinal cord injury (SCI) have an increased prevalence of
      cholelithiasis. The goal of this study was to clarify the presentation and
      management of symptomatic gallstone disease in patients with SCI. We performed a
      retrospective study of presentation of gallstone complications in patients with
      SCI who underwent cholecystectomy for complications of gallstone disease. The
      West Roxbury Veterans Administration Medical Center SCI registry (605 patients)
      was searched for patients who had undergone cholecystectomy more than 1 year
      after SCI (35 patients). Gallbladder disease profiles for the 35 patients
      undergoing cholecystectomy for complications of gallstone disease were prepared,
      including demographics, clinical presentation, diagnostic studies, operative and
      pathologic findings, and postoperative complications. All patients were white.
      Thirty-four were male and the mean age was 50 years (range 35 to 65 years). The
      majority of patients (66%) complained of right upper quadrant abdominal pain,
      even those patients with SCI at high (i.e., cervical) levels. Of the 35 patients
      in our study group, 22 (63%) had biliary colic and chronic cholecystitis, nine
      (26%) had acute cholecystitis (gangrenous cholecystitis in two), two (6%) had
      choledocholithiasis symptoms or cholangitis, and two (6%) had gallstone
      pancreatitis. Major perioperative morbidity occurred in two (6%) of the 35
      patients (pulmonary embolus; intraoperative hemorrhage), and there were no
      deaths. In the great majority of patients with SCI, cholelithiasis presents with
      chronic pain and not with life-threatening complications. Our findings suggest
      that presentation is no more acute in patients with SCI than in the general
      population. Characteristic symptoms and signs are not necessarily obscured by SCI
      injury, regardless of the level.

PMID- 11307103
TI  - Current concepts in the management of obesity. An evidence based review.
AB  - The increasing prevalence of overweight and obesity is an important public health
      problem contributing to significant excess in morbidity and mortality. A cross
      sectional national epidemiological household survey showed that the prevalence of
      obesity in female Saudi subjects was among the highest reported. Obesity is a
      complex multifactorial chronic disease that develops from an interaction of
      genotype and the environment. Our understanding of how and why obesity develops
      is incomplete, but involves the integration of social behavioral, cultural
      physiological, metabolic and genetic factors. While there is agreement about
      health risks of over weight and obesity, there is less agreement about their
      management. Primary health care services should play the dominant role for
      obesity management. Family physicians need to assess the patient's readiness to
      enter weight loss therapy and take appropriate steps for motivation. Weight loss
      and weight maintenance therapy should employ the combination of low caloric diet,
      increased physical activity, and behavioral therapy. Weight loss drugs may be
      used as part of comprehensive weight loss program. Weight loss surgery is an
      option for carefully selected patients with severe obesity Body Mass Index
      greater than 40. After successful weight loss, a program consisting of dietary
      therapy, physical activity, and behavioural therapy, which should be continued
      indefinitely, enhances the likelihood of weight loss maintenance.

PMID- 11307104
TI  - Hepatic artery thrombosis after orthotopic liver transplantation.
AB  - OBJECTIVE: Hepatic artery thrombosis after liver transplantation is uncommon, but
      represents an important cause of morbidity and mortality. The aim of this study
      is to identify the possible risk factors for the development of hepatic artery
      thrombosis, and the impact of hepatic artery thrombosis on the patients and graft
      survival. METHODS: Between January 1994 and June 1998, we reviewed
      retrospectively a series of 86 liver transplant procedures performed on 81 adult
      patients. Arterial anomalies of the donor graft, rejection episodes, cold
      ischemia time, ABO matching, the use of blood/fresh frozen plasma during and
      after surgery, and the use of heparin as prophylactic anticoagulation therapy
      were examined as a possible contributing risk factors for the development of
      hepatic artery thrombosis. RESULTS: Hepatic artery thrombosis occurred in 7
      procedures out of 86 (9%). Early cases of Hepatic artery thrombosis within 15
      days after transplant occurred in 4 patients. Late thrombosis occurred in 3
      patients. Analysis of potential risk factors for the development of hepatic
      artery thrombosis was carried out. Five out of 40 patients who did not received
      prophylactic heparin had hepatic artery thrombosis (12.5%), while only 2 out of
      46 patients who received prophylactic heparin had hepatic artery thrombosis 4%.
      On the other hand, 6 out of the 7 patients developed hepatic artery thrombosis
      received more than 5 units of blood transfusion during the transplant procedure
      (11%) while only one patient developed hepatic artery thrombosis who received
      less than 5 units intra-operatively (3%). Management of hepatic artery thrombosis
      cases were carried out in the form of: thrombectomy (n = 1), thrombectomy
      followed by retransplantation (n = 2), and non-surgical or conservative treatment
      (n = 4). The overall survival rate was (43%) (3 out of 7). Out of four deaths, 3
      were directly related to hepatic artery thrombosis while the cause of death iin
      the remaining patients was attributed to pulmonary sepsis. CONCLUSION: Early
      hepatic artery thrombosis leads to death unless quick retransplantation follows.
      Conservative treatment for the late onset hepatic artery thrombosis on occasion
      has been useful. The use of postoperative prophylactic anticoagulation therapy
      might be of benefit in the prevention of hepatic artery thrombosis after liver
      transplantation. Increased transfusion requirement for red blood cells during
      transplant procedure was independently associated with increase incidence of
      hepatic artery thrombosis.

PMID- 11307105
TI  - Pattern of acute pancreatitis.
AB  - OBJECTIVE: The aim of this communication was to study the clinical pattern of
      acute pancreatitis with special reference to aetiology, severity, seasonal
      variation and outcome in the high altitude region of Asir. METHODS: This is a
      cross-sectional, hospital-based study. All consecutive cases of acute
      pancreatitis admitted to Asir Central Hospital, Abha, Saudi Arabia over a two and
      half-year period (May 1996 - October 1998) were included. Clinical and laboratory
      data were analyzed to determine the severity of the attack according to Ranson's
      criteria. RESULTS: There was a total of 73 attacks of acute pancreatitis in 69
      patients. Mean patient age was 51.01 years (range = 13-120 years) and the male to
      female ratio was 0.6:1. In 68.5%, gallstones were the associated cause and
      idiopathic acute pancreatitis was diagnosed in 25%. Using Ranson's severity
      prediction criteria, 44% of the attacks were classified as "severe", but only 22%
      of the patients so classified developed complications. Pseudocysts and Pancreatic
      abscess complicated three cases. Complications were significantly correlated with
      cold seasons (P = 0.04), intervention by Endoscopic retrograde
      cholangiopancreatography (P = 0.02) and severity (P = 0.02). CONCLUSION: This
      study revealed that acute pancreatitis seen in Asir region is predominantly
      biliary-associated and is more frequent in females. Although near half of the
      attacks were classified as severe pancreatitis, according to Ranson's criteria,
      complications occurred in only 22% of the attacks and this may indicate that
      Ranson's criteria needs to be modified before application in our setting.

PMID- 11307106
TI  - Knowledge of hypoglycemia by primary health care centers registered diabetic
      patients.
AB  - OBJECTIVE: To assess the knowledge of diabetic patients about symptoms of
      Hypoglycemia, and the variables that may be associated with that knowledge.
      METHODS: A cross-sectional study of 1039 diabetic subjects, registered in the
      urban and rural primary health care centers of Makkah. The tool of data
      collection was a structured questionnaire. The parameters of the study were lack
      of knowledge about hypoglycemia measured as knowledge of individual symptoms; and
      the proportions of patients with poor knowledge score. RESULTS: The frequency of
      lack of knowledge of symptoms of hypoglycemia was around 50% of subjects. Two
      third of subjects had a poor knowledge score. Main variables significantly
      associated with poor knowledge score were male gender (P < 0.001), low education
      (P < 0.0001), non-compliance with treatment (P < 0.02), and lack of knowledge
      about hypoglycemia (P < 0.00001). CONCLUSION: There is a need for health
      education of diabetic subjects about symptoms of hypoglycaemia, in order to deal
      with it in an effective way.

PMID- 11307107
TI  - Chromosome studies in male patients suffering from infertility.
AB  - OBJECTIVE: The goal was to estimate the contribution of chromosome anomalies in
      the Iraqi infertile males. METHODS: Sixty-four male patients were included in the
      present study. Blood culture and chromosomal harvesting were conducted according
      to standard methods. RESULTS: The percentage of normal karyotype was 87.5%. The
      number of abnormal karyotypes constitute about 12.5%. In our azoospermic
      patients, about 11% of patients stated to have abnormal karyotype comparing to
      15% in oligospermic patients. On the other hand, sex chromosomal anomalies were
      detected in 4 patients with azoospermia. No autosomal anomalies were found in
      this group. Meanwhile, 3 patients with sex chromosomal anomalies were recorded in
      oligospermic patients. The unique autosomal anomaly was detected in one
      oligospermic patient. CONCLUSION: Karyotyping of subfertile males will still be
      important not only from a diagnostic viewpoint, but even more importantly, in
      order to gain a better understanding of gametogenic impairment, which is
      associated with chromosomal abnormalities. Moreover, the value of cytogenetic
      screening is emphasized since this group of chromosomally abnormal patients can
      be excluded from conventional treatment.

PMID- 11307108
TI  - Developmental risk factors for unintentional childhood poisoning.
AB  - OBJECTIVE: To identify main risk factors for unintentional childhood poisoning in
      Ahwaz, Iran and to suggest possible causes and preventative measures. METHODS:
      This is an epidemiological description and a case-control study. The study was
      undertaken in Ahwaz, Iran in 1996-1997. Cases were 100 children who were taken to
      one of the 17 Accident and Emergency Departments due to poisoning. For every case
      two controls were selected. Age, gender, hospital and date of attendance to
      Accident and Emergency Department were matched between cases and controls. All
      parents of the children were interviewed by using a questionnaire that included
      demographic and poisoning characteristic information. RESULTS: Children without
      adult supervision (odds ratio = 4.8), and those with previous poisoning (odds
      ratio = 5.2) were at increased risk of poisoning (P < 0.05). Drug poisoning was
      more common among children (60%), and most poisoning occurred inside the home
      (89%). Boys (65%), and children aged 2-4 years (79%) had more poisoning than
      others. In 75% of cases, poisonous products were accessible. CONCLUSION: Adequate
      parental supervision and safe packing, storage and disposal of potentially
      hazardous substances could be the most important activities for prevention of
      childhood poisoning. Furthermore, manufactures and traders must by law put
      certain toxic household products and drugs in child resistant containers, and
      mark toxic medicines with warning labels or signs.

PMID- 11307109
TI  - An epidemiological study of neonatal necrotizing enterocolitis.
AB  - OBJECTIVE: To study epidemiology including various risk factors incorporated in
      neonatal necrotizing enterocolitis in Kashmir. METHODS: A retrospective hospital
      based study on 3235 neonates admitted in Neonatal Intensive Care Unit of Sheri
      Kashmir Institute, were evaluated. Forty two were diagnosed as cases of Neonatal
      Necrotizing Enterocolitis on the basis of various clinical and radiological
      parameters and grouped in 3 stages as per modified Bell's classification. The
      case records of these 42 babies and 303 of the control group were reviewed for
      the purported risk factors and recorded on pretested proforma and finally
      statistically analyzed. RESULTS: Over a period of 10 years, we documented
      necrotizing enterocolitis in 42 neonates, with an incidence of 1% of all Neonatal
      Intensive Care Unit admissions and 1% of all live births. Eighty one percent were
      less than 2000 gms and 76% less than 36 weeks of gestation. Twenty four percent
      had stage I disease, 33% had stage II, and 43% babies had stage III disease.
      Multiple risk factors were present in these babies, with significant differences
      among Necrotizing Enterocolitis and the control group of patients, particularly
      hypothermia (P < 0.001), respiratory distress (P < 0.05), polycythemia (P <
      0.001) acidosis (P < 0.01), sepsis (P < 0.001), enteral feeding and asphyxia (P <
      0.001). Of the 59 babies (< 2000 gms) with hypothermia (< 35 degrees C), 39%
      developed Necrotizing Enterocolitis, compared to 4% babies (11/278), who did not
      have hypothermia, statistically a significant finding. Mean birth weight and
      gestational age were lower than in control group (P < 0.05). The age of
      presentation was 5.2 +/- 4.0 days and majority (81%) presented during first week
      of life, most severe cases presenting earlier than the mild cases. Severity of
      Necrotizing Enterocolitis as per modified Bell's classification and mortality was
      inversely related to birth weight and gestational age. One hundred percent
      mortality was noted in the babies, with birth weight less than 1000 gms and
      gestational age less than 28 weeks. The overall mortality was 45%, for stage I,
      20%; for stage II, 36% and 67% for stage III. Necrotizing Enterocolitis cases
      accounted for maximum mortality in Neonatal Intensive Care Unit than in control
      group (P < 0.001). CONCLUSION: Recognition of factors such as prematurity, low
      birth weight, hypothermia, asphyxia and their timely prevention would help in
      reducing morbidity and mortality due to Necrotizing Enterocolitis.

PMID- 11307110
TI  - Comparative in-vitro activity of trovafloxacin and other related drugs against
      isolates of streptococcus oralis.
AB  - OBJECTIVE: The in-vitro activity of trovafloxacin a new quinolone was compared
      with that of ciprofloxacin, erythromycin, various b-lactam and other appropriate
      antibiotics such as vancomycin, teicoplanin and clindamycin against 60 isolates
      of S. oralis. METHODS: Minimal inhibitory concentration was performed using the
      agar dilution technique and micro-titer method. In addition minimal bactericidal
      concentration and time-kill studies were carried out to estimate the bactericidal
      activity of trovafloxacin against S. oralis isolates. RESULTS: Trovafloxacin
      showed a four-fold increase in activity over ciprofloxacin, with a narrow minimal
      inhibitory concentration range, MIC50 and mode values of 0.25 mg/l. Although the
      minimal inhibitory concentrations of trovafloxacin for S.oralis were relatively
      high compared to all the antibiotics tested. The in-vitro bactericidal activity
      of Trovafloxacin was greater than all other antibiotics against S. oralis. Five
      out of 10 isolates showed there was a 100% kill within 6 hours of contact; in all
      other cases, the kill time was between 6 and 24 hours. CONCLUSION: Overall,
      trovafloxacin showed superior minimal inhibitory concentration, bactericidal
      concentration and kill time when compared with different antibiotics.

PMID- 11307111
TI  - Audit of management of respiratory infections among children.
AB  - OBJECTIVE: To study the pattern of drugs prescribing for acute respiratory
      infections among young children under 5 years and to establish the first step in
      auditing acute respiratory infections management in two large Primary Health Care
      Centers in Abha, Asir region. METHODS: Three hundred and thirteen prescriptions
      of children less than 5 years old were selected randomly and evaluated for: age,
      sex, nationality, and drugs prescribed in two large Primary Health Care Centers
      in Abha city, Asir region, Saudi Arabia. The medical records of children who
      received antibiotics were further evaluated for: process of recording symptoms
      and signs and appropriateness with diagnosis. Structures of acute respiratory
      infections care in both Primary Health Care Centers were evaluated in both
      centers using checklist and scoring system. RESULTS: Common cold was the most
      common diagnosis encountered. Antibiotics were the most common prescribed drugs
      in both Primary Health Care Centers. Less than one third of files revealed
      appropriate recording of history and physical examination. CONCLUSION: There were
      inadequate structures in both Primary Health Care Centers which negatively
      affected the process of acute respiratory infections care in both centers. Urgent
      providing of those structures and establish continuing medical education for the
      Primary Health Care Center team and health education of the community about acute
      respiratory infections are two important priorities at both Primary Health Care
      Centers.

PMID- 11307112
TI  - Exhaled nitric oxide levels in exacerbations of asthma, chronic obstructive
      pulmonary disease and pneumonia.
AB  - OBJECTIVE: Nitric oxide is known to be present in the exhaled air of normal
      subjects and at higher concentrations in asthmatics. The aim of this study was to
      measure exhaled nitric oxide levels in patients admitted to hospital with acute
      exacerbations of asthma, or chronic obstructive pulmonary disease, or with
      pneumonia. METHODS: Within 24 hours of admission exhaled nitric oxide levels were
      measured by a chemiluminescent analyzer in 11 patients with acute sever asthma,
      19 patients with acute exacerbation of chronic obstructive pulmonary disease, and
      in 12 patients with pneumonia. In asthmatics measurements were made on 3
      occasions, at day 1, 4, and 28 and were related to changes in peak expiratory
      flow rate. RESULTS: On admission median exhaled nitric oxide levels (range) were
      significantly higher in asthmatics 22 (9.3-74) parts per billion in comparison to
      patients with chronic obstructive pulmonary disease 10.3 (2.7-34) parts per
      billion; p < 0.01, pneumonia 7 (4-17) parts per billion; p<0.001, and normal
      subjects 8.7 (5-13.3) parts per billion; p < 0.001. Following treatment the
      asthmatics had a significant reduction in their exhaled nitric oxide levels from
      22 (9.3-74) parts per billion on day 1 to 9.7 (5.7-18.3) parts per billion on day
      28; p = 0.005. Peak expiratory flow rate measurements increased from 200 (120
      280) l/min on day 1 to 280 (150-475) l/min on day 4; p < 0.05 and to 390 (150
      530) l/min on day 28; p < 0.01. A strong negative correlation existed between
      peak expiratory flow rate measurements and exhaled nitric oxide levels in
      asthmatics on day 28 (r = -0.70; p = 0.017). CONCLUSION: Acute exacerbations of
      asthma are associated with increased levels of exhaled nitric oxide in contrast
      to exacerbations of chronic obstructive pulmonary disease and acute pneumonia.
      Exhaled nitric oxide may be a useful indirect marker of asthmatic airway
      inflammation. The differing time course of response of nitric oxide to peak flow
      measures suggests that these two measures are reflecting differing airway events.

PMID- 11307113
TI  - Recurrence risk after a first febrile convulsion.
AB  - OBJECTIVE: Fever is the most common cause of convulsions, in infancy and
      childhood. Parents usually are concerned by the risk of recurrence. Our aim is to
      determine this risk of subsequent convulsions within the first year of the first
      episode of convulsion. METHODS: This is a prospective study over one year, May 97
      to April 98 in which all children with first febrile seizure were enrolled.
      RESULTS: There were two hundred and thirty six children who had their first
      febrile convulsion within the study period. Male-to-female ratio was 1.2:1; the
      mean age at onset was 19 months (standard deviation 14.4). Generalized seizure
      occurred in 95.6% of the patients with an average duration of 7 minutes (SD 6.4).
      Ten percent of patients needed anticonvulsant drugs to stop convulsion. Seizure
      clusters occurred in 13.6 %, and complex febrile seizure was noticed in 21%.
      Family history was positive for epilepsy in 6.6% and febrile convulsions in 22%.
      Recurrence within a year from onset occurred in 52 (21%) of the patients. Factors
      associated with recurrence were: male sex, as male to female ratio was 2.25:1 (P
      = 0.02) and history of seizure clusters, 23/52, 44% (P = 0.00001). CONCLUSION:
      Risk factors for recurrence noted were male sex, and complex febrile seizures.

PMID- 11307114
TI  - In situ measurements of muscle fiber conduction velocity in Duchenne muscular
      dystrophy.
AB  - OBJECTIVE: To measure the muscle fiber conduction velocity in Duchenne muscular
      dystrophy patients. METHODS: The muscle fiber conduction velocity of the biceps
      brachii and tibialis anterior was measured with the needle electrode. Eighteen
      controls and 32 Duchenne muscular dystrophy patients were studied. Clinical
      neurological examination, serum cretin kinase level estimation, conventional
      electromyogram were carried out for every individual and 17 of the Duchene
      muscular dystrophy patients were biopsied for further histological and
      histochemical examination. RESULTS: The muscle fiber conduction velocity of the
      control group showed good reproducibility. The frequent distribution of the
      Duchenne muscular dystrophy data characterized by multi-peaks curve as compared
      to the control group. This is demonstrated as significant slowing (P < 0.005) of
      the muscle fiber conduction velocity in the two muscle examined of the patients
      group. CONCLUSION: The slowing of the muscle fiber conduction velocity is
      proposed to be due to the small size of the regenerating and splitting fibers.
      The multi-peaks frequency distribution curve indicates a great variability in the
      muscle fiber diameter. The muscle fiber conduction velocity is a useful tool for
      diagnosing myopathies.

PMID- 11307115
TI  - Satisfaction and correlates of patients' satisfaction with physicians' services
      in primary health care centers.
AB  - OBJECTIVE: To estimate quantitatively consumers' satisfaction and correlates of
      satisfaction with physicians' services provided by Ministry of Health Primary
      Health Care Centers in attending consumers. METHODS: Consumers (n = 540)
      attending the selected Primary Health Care Centers in Riyadh were asked about
      their satisfaction with physician's services. Eight Primary Health Care Centers
      were randomly selected according to the geographical location, two from each
      geographical zone. Seventy-five subjects were selected systematically where every
      tenth Saudi aged 15 years and above who visited the selected Primary Health Care
      Centers during the study period was chosen. Data was collected via a self
      administered pilot tested, internally consistent patient satisfaction
      questionnaire which included socio-demographic characteristics as well as the
      overall and differential satisfaction with the different aspects of physicians'
      services in the selected Primary Health Care Centers rated in a scale of 1 5
      points, the higher the score the higher the satisfaction. RESULTS: The results
      revealed that males constituted 60%, and 58% of all patients were married, more
      than 60% were employees and more than 70% have a monthly income of less than 6000
      Saudi Riyals. Almost 95% have an open file in the Primary Health Care Center and
      39% think that the distance to the Primary Health Care Center is far or very far.
      The summary satisfaction score was 3.77 points and the mean satisfaction with the
      services provided by physicians was 2.56 points out of a maximum of 5 points The
      highest satisfaction was for discussing psychological aspects of patients'
      problems (2.96 points) and the lowest was for attentive listening to patients'
      complaints (2.22 points). Physicians' communication skills were more satisfactory
      to patients than their professional skills and satisfying patients' wishes scored
      the lowest satisfaction- Unskilled laborers, literate patients and patients with
      higher income showed significantly higher mean satisfaction while students,
      illiterates, those aged less than 50 years and patients with income less than
      6000 Riyals per months scored the lowest satisfaction. The longer the distance
      travelled the lower the satisfaction scores but having a file or not was not
      related to satisfaction. CONCLUSION: Some physicians' service items need
      corrective intervention and students and young patients appear to need more
      attention.

PMID- 11307116
TI  - Clinicopathological study of pilomatricoma.
AB  - OBJECTIVE: To study the clinical and histopathologic spectrum of pilomatricoma,
      the benign tumor of hair matrix. METHODS: Retrospective review of 27 cases of
      pilomatricoma (Calcifying epithelioma of Malherbe) reported at Bahrain Defence
      Force Hospital from 1993-1999. RESULTS: Most of the cases were confused
      clinically with sebaceous cysts. Seventy eight per cent of the cases occurred
      below the age of 30 years. Female to male ratio was 5:4. Head, neck and upper
      limb were the most common sites for pilomatricoma. The size of the tumors ranged
      from between 4-35 mm in diameter. Tumors were encapsulated and solid composed of
      shadow and basophilic cells, and stroma containing varying amounts of
      calcification, ossification and inflammatory cells. CONCLUSION: Pilomatricomas
      have a wide variety of clinical characteristics and are often misdiagnosed with
      other skin conditions. They should be considered along with other benign and
      malignant conditions in the clinical differential diagnosis of solitary firm skin
      nodules especially those, which occur in the head, neck and upper limb.

PMID- 11307117
TI  - Third degree tears and episiotomy.
AB  - OBJECTIVE: To investigate the relation of episiotomy to third degree perineal
      tears, and to detect the rate, indications and risk factors of both episiotomy
      and third degree perineal tears. METHODS: Between 1994 and 1999, 17,559 singleton
      vaginal deliveries were retrospectively investigated to find frequency, risk
      factors and relation of episiotomy to third degree Perineal tears. To avoid the
      affect of confounding factors, we analyzed a sub-sample that included only vertex
      presentation with spontaneous occipito-anterior vaginal deliveries. RESULTS: The
      incidence of episiotomy was 39%. Third degree tears occurred in 1% of the
      deliveries with episiotomy in 0.2% of the deliveries without episiotomy. Third
      degree tears were more commonly occurred in primiparae, instrumental deliveries,
      episiotomy, and birth weight more than 4 kg. After stratification for birth
      weight and parity, no relation between episiotomy and third degree tear was
      found. CONCLUSION: In uncomplicated deliveries, no significant relation between
      third degree perineal tear and episiotomy was found.

PMID- 11307118
TI  - Living-related liver transplantation.
AB  - We report here, the first pediatric living-related liver transplant in Saudi
      Arabia and the Middle East. Our patient is a 2 year old girl with a diagnosis of
      progressive familial intrahepatic cholestasis, causing intractable pruritus and
      failure to thrive requiring liver transplantation. The child was successfully
      transplanted using a segment of her mother's liver for living-related liver
      transplantation. Two years post-transplantation the patient is doing well. With
      the ongoing crises in cadaveric organ availability and the high prevalence of
      pediatric liver disease, living related liver transplantation is an ideal
      solution to this difficult and challenging problem.

PMID- 11307119
TI  - Hepatocellular carcinoma in Najran.

PMID- 11307120
TI  - An experience with rigid oesophagscopy.

PMID- 11307121
TI  - Ten tips for writing fair multiple choice questions.

PMID- 11307122
TI  - Sequential bilateral total knee arthroplasty under 1 anesthetic in patients > or
      = 75 years old: complications and functional outcomes.
AB  - The objectives of this study were to determine the perioperative surgical and
      medical risks associated with sequential bilateral total knee arthroplasty (TKA)
      in patients > or = 75 years old and to assess their functional status and overall
      level of satisfaction at follow-up. Study participants were 82 consecutive
      patients > or = 75 years old who underwent a sequential bilateral TKA and 82
      matched patients who underwent a unilateral TKA. There were 46 postoperative
      complications in the bilateral TKA group compared with 27 in the unilateral TKA
      group (P = .003). Postoperative cardiovascular complications were significantly
      greater in the sequential bilateral TKA group and were associated significantly
      with preoperative cardiovascular comorbidity. The mean Modified Hospital for
      Special Surgery knee score was rated as good (mean, 63.5 out of 80), and 95% of
      patients rated their knees as excellent or good at follow-up. Sequential
      bilateral TKA in patients > or =75 years old results in high patient satisfaction
      and good functional status at follow-up; however, there is an increased risk of
      cardiovascular complications during the postoperative period in bilateral
      sequential TKA patients when compared with a matched cohort of unilateral TKA
      patients.

PMID- 11307123
TI  - Total knee arthroplasty using the S-ROM mobile-bearing hinge prosthesis.
AB  - A retrospective study was performed on 15 patients receiving 16 S-ROM mobile
      bearing hinge total knee prostheses that were evaluated with at least a 2-year
      follow-up (range, 27-71 months). Indications for its use included severe
      instability and bone loss. The average patient age was 63 years (range, 33-83
      years). There were 15 revision arthroplasties and 1 primary arthroplasty. Knee
      Society scores showed notable improvement in pain, motion, and stability (33.6
      preoperatively vs 76.5 postoperatively; P <.0001) and approached significant
      improvement in function (29.2 preoperatively vs 43.5 postoperatively; P =.11).
      After excluding a patient with a traumatically ruptured patellar tendon, the
      probability of the latter comparison improved (P <.01). There was no evidence of
      loosening, and complete bone apposition was seen in nearly all cases. A high
      percentage of satisfactory results can be achieved when using this mobile-bearing
      hinge knee prosthesis for these indications.

PMID- 11307124
TI  - Systemic fat and thrombus embolization in patients undergoing total knee
      arthroplasty with regional heparinization.
AB  - A double-blind, randomized, controlled study was undertaken to determine if a
      technique of intraoperative anticoagulation would decrease the incidence or
      severity of venous embolization after tourniquet release during total knee
      arthroplasty. Sixty-six patients were randomized to receive either the heparin or
      placebo treatment. Transesophageal echocardiography was performed before and
      after tourniquet release to detect embolic material in the right atrium.
      Transient opacification of the right atrium was observed in all patients within
      the first 30 seconds after tourniquet release. Regional limb heparinization is
      not effective in reducing the intensity of right atrium opacification because
      much of the echogenic material was composed of fat rather than thrombus.

PMID- 11307125
TI  - A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty.
AB  - Deep venous thrombosis (DVT) is common in total knee arthroplasty (TKA). Because
      of the rarity of the most serious outcomes, most randomized controlled trials
      lack the power to analyze these outcomes. A meta-analysis was performed for
      agents used in DVT prophylaxis in TKA employing a Medline literature search.
      Study inclusion criteria were randomized controlled trials comparing prophylactic
      agents in elective TKA with mandatory screening for DVT by venography. Fourteen
      studies (3,482 patients) met inclusion criteria. For total DVT, all agents except
      dextran and aspirin protected significantly better than placebo (P < .0001). For
      proximal DVT rates, low-molecular-weight heparin was significantly better than
      warfarin (P = .0002). There was a trend that aspirin was better than warfarin (P
      = .0106). No significant difference was found for symptomatic pulmonary embolism,
      fatal pulmonary embolism, major hemorrhage, or total mortality.

PMID- 11307126
TI  - Determining femoral rotational alignment in total knee arthroplasty: reliability
      of techniques.
AB  - Several anatomic axes routinely are used for determining femoral rotational
      alignment in total knee arthroplasty. The purpose of this study was to determine
      the reliability of these techniques. The transepicondylar axis, anteroposterior
      axis, and balanced flexion gap tension line were identified relative to the
      posterior condylar axis in 8 fresh frozen cadaver knees by 3 independent
      observers. The flexion-extension axis was defined in each knee for comparison.
      The anteroposterior and balanced tension axes defined most reliably the flexion
      extension axis and best balanced the flexion gap with no significant
      interobserver differences. The transepicondylar axis was less predictable and
      significantly more externally rotated than the anteroposterior axis (P < .005)
      and the balanced tension line (P < .00001). Flexion gap tensioning may offer
      superior reliability because of its independence of obscured or distorted bone
      landmarks.

PMID- 11307127
TI  - The efficacy of intra-articular analgesia after total knee arthroplasty in
      patients with rheumatoid arthritis and in patients with osteoarthritis.
AB  - The pain relief provided by intra-articular injection of morphine plus
      bupivacaine after total knee arthroplasty (TKA) plus partial synovectomy in
      patients with rheumatoid arthritis was compared with pain relief after TKA alone
      in patients with osteoarthritis. There were lower pain scores, a much smaller
      requirement for systemic analgesics, longer duration until the first requirement
      of systemic analgesics, and improvement in the range of motion of the knee joint
      in the patients who received intra-articular injection of analgesics. There was
      more pronounced postoperative analgesia in the patients with rheumatoid arthritis
      than in the patients with osteoarthritis in the study groups that received intra
      articular injection of analgesics.

PMID- 11307128
TI  - Clinical and radiographic results of cementless AML total hip arthroplasty in
      young patients.
AB  - A retrospective study was undertaken of the radiographic and clinical results and
      complications of 52 cementless (AML) total hip arthroplasties in 52 patients with
      a mean age of 48.3 years. The follow-up ranged from 9 to 12 years with a mean of
      10.5 years. Of the patients, 88% had good or excellent results. Forty-two
      patients (81%) complained of anterior thigh pain at 3 months after surgery when
      weight bearing was allowed. The pain continued for a mean period of 4.3 months.
      In 4 patients (8%), this pain persisted after the first postoperative year.
      Calcar resorption was seen in 21 patients (40%), and 16 patients (31%) showed
      clinically insignificant heterotopic ossification. Four patients required
      revisions: 1 for acetabular loosening, 1 for persistent thigh pain, and 2 for
      massive osteolysis of the proximal femur. There were no dislocations, infections,
      thromboembolic events, or neurologic injuries.

PMID- 11307129
TI  - Total knee arthroplasty after ipsilateral peripheral arterial bypass graft: acute
      arterial occlusion is a risk with or without tourniquet use.
AB  - A retrospective review was done of the total joint registry at the Mayo Clinic,
      Rochester, Minnesota, which contains the computerized records of 19,808
      consecutive total knee arthroplasties (TKAs) including primary and revision that
      were performed from 1970 to 1997. From that database, 9 patients were found to
      have had a TKA after an ipsilateral peripheral arterial reconstruction. One
      patient had had bilateral peripheral arterial reconstruction followed by
      bilateral TKA, and 10 TKAs were reviewed. The medical records were reviewed
      retrospectively with particular attention given to the type of peripheral bypass
      surgery performed, the bypass graft source, the timing of the bypass surgery
      relative to TKA, the use of a tourniquet at the time of TKA, and the occurrence
      of complications after TKA. Of the 10 TKAs, 2 patients had acute arterial
      occlusion. One patient had a tourniquet, and the other patient did not. There was
      not a statistical correlation between graft type, tourniquet use, timing of
      surgery, postoperative anticoagulation, and occurrence of arterial occlusion.
      There is a marked risk of acute thrombosis of an ipsilateral arterial bypass
      graft after TKA that cannot be eliminated by performing the TKA without a
      tourniquet. Careful monitoring of the vascular status of the limb is required in
      the early postoperative period to detect arterial compromise. Should limb
      ischemia be suspected, an emergent vascular surgery consultation is required, and
      arterial flow to the lower extremity must be re-established.

PMID- 11307130
TI  - Preoperative planning for lower extremity osteotomies: an analysis using 4
      different methods and 3 different osteotomy techniques.
AB  - Lower extremity osteotomy is a common procedure for managing deformity and
      unicompartmental gonarthrosis. One consideration not typically addressed is how
      the osteotomy will affect the leg length of the extremity. This article presents
      a numerical analysis of apparent leg-length change before and after osteotomy
      surgery. It also compares the differences resulting from the 3 different major
      types of osteotomies (closing wedge, opening wedge, and dome). Three different
      preoperative planning methods and a fourth intraoperative technique were studied.
      Using different methods of preoperative planning with the same osteotomy
      technique resulted in leg-length changes of 0.5 to 3 mm. Differences > 7 degrees
      in lower extremity alignment may result depending on the planning method used.
      When comparing osteotomy techniques, 2 cm in leg-length difference was
      calculated.

PMID- 11307131
TI  - Infection after total joint arthroplasty in patients with human immunodeficiency
      virus or intravenous drug use.
AB  - Patients with intravenous drug use (IVDU) and patients with human
      immunodeficiency virus (HIV) with painful joint arthrosis present a difficult
      treatment decision. The purpose of this study was to determine the rate of deep
      periprosthetic infection in patients with HIV or IVDU after total joint
      arthroplasty (TJA). Twenty-nine patients with HIV or a history of IVDU or both
      underwent TJA. Of 28 HIV-positive patients undergoing TJA, 4 (14%) developed
      infections. Two of 8 joints (25%) in the IVDU group developed an infection. Two
      of 5 joints (40%) with both IVDU and HIV developed a deep infection. Patients
      with HIV or a history of IVDU are more likely to develop a deep infection
      compared with other patients undergoing TJA. The decision to proceed with TJA in
      HIV-positive and IVDU patients should be made only after weighing the ratio of
      risks and benefits.

PMID- 11307132
TI  - Use of continuous passive motion after total knee arthroplasty.
AB  - Sixty primary total knee arthroplasties in 43 Chinese patients were included into
      a prospective study. Twenty-six patients who had unilateral knee arthroplasty
      were randomized to receive continuous passive motion (CPM) or immobilization in
      the first week. The 2 groups of patients were comparable in demographic data and
      preoperative knee range of motion (ROM). In 17 patients who had 1-stage
      sequential bilateral arthroplasties, one side had CPM and the other side was
      immobilized. The active knee ROM was assessed regularly until 1 year after the
      operation. For all patients, the early active knee ROM in the CPM group was
      significantly better than the immobilization group. There was no difference after
      7 days, however. For patients who had 1-stage bilateral total knee
      arthroplasties, the active knee ROM was significantly better on the CPM side
      until day 28. After 4 weeks, there was no difference between the CPM group and
      the immobilization group. Immobilization after total knee arthroplasty does not
      preclude good ROM.

PMID- 11307133
TI  - Primary Charnley total hip arthroplasty: a comparison of American and Japanese
      cohorts followed for 10-20 years.
AB  - Primary Charnley total hip arthroplasties (THAs) followed for 10 to 20 years were
      compared between an American (183 sockets and 178 femoral prostheses) and a
      Japanese (145 sockets and 148 femoral prostheses) series, each performed by a
      single surgeon at a single hospital using similar techniques. The primary
      etiology was developmental dysplasia of the hip (70%) in the Japanese series and
      primary osteoarthrosis (50%) in the American series. Radiographic socket survival
      was inferior in the Japanese series at 4- to 11-year follow-up, which was
      attributed mainly to the etiologic difference. The American patients had higher
      levels of postoperative activity and developed more accelerated polyethylene
      wear, which may lead to an increased loosening rate of sockets > or = 10 years
      after THA. The American series had higher rates of femoral revision at > or = 9
      years follow-up, which was attributed mainly to lower canal flare indices in that
      series.

PMID- 11307135
TI  - Noncemented Cathcart elliptical head endoprosthesis for displaced femoral neck
      fractures.
AB  - A total of 93 patients (95 hips) undergoing unipolar noncemented elliptical head
      endoprosthetic replacement for an acute displaced femoral neck fracture were
      reviewed clinically and radiographically at an average follow-up of 28 months.
      The 12-month mortality rate was 22%. The medical complication rate was 15%, and
      the surgical complication rate was 19%. At most recent follow-up, 66% of patients
      used an assist device for ambulation or were nonambulatory. Of patients, 64%
      required full-time nursing care. Radiographically, subsidence of the component
      was identified in 66% of the hips and acetabular erosion in 29%. More than half
      of these patients had complaints of either thigh or groin pain. Hips with
      evidence of subsidence had a statistically significant greater length of follow
      up (36 months) compared with hips that did not show subsidence (18 months; P =
      .014). Noncemented unipolar replacement for displaced femoral neck fractures is
      an accepted form of treatment. In this group of predominantly male patients,
      noncemented elliptical head unipolar replacement was associated with a high
      medical and surgical complication rate as well as poor clinical and radiographic
      results.

PMID- 11307134
TI  - Change in pain and function while waiting for major joint arthroplasty.
AB  - The objective of this study was to examine the change in pain and physical
      function that occurs while waiting for major arthroplasty. Data were collected
      prospectively from a cohort of 313 patients who were waiting > 1 month for total
      hip arthroplasty or total knee arthroplasty. The WOMAC and the SF-36 health
      status instruments were administered at the time the patient was placed on the
      waiting list and again just before surgery. Minimal amounts of change in pain and
      physical and psychosocial function occurred for hip and knee arthroplasty
      patients while they waited. Overall, waiting time did not appear to have a
      negative impact on the amount of pain and dysfunction experienced.

PMID- 11307136
TI  - Fuji film and ultrasound measurement of total knee arthroplasty contact areas.
AB  - This article describes tibiofemoral contact area measurement results from tests
      on 1 commercial total knee arthroplasty (TKA) using 2 experimental methods-fuji
      film and diagnostic ultrasound. The study presents a novel diagnostic ultrasound
      technique developed specifically for measuring TKA contact areas. Because most
      experimental investigations have been concerned with interimplant comparison,
      this article is one of few parametric TKA studies in the literature. Fuji film
      and ultrasound provide lower and upper bound contact area measurements based on
      their physical operating principles; this implies that no single measurement
      method can be relied on exclusively to glean contact area data. Designers should
      be cautious in using contact area and contact stress as the exclusive predictors
      of TKA failure.

PMID- 11307137
TI  - The use of handheld cement sample as a guide to the setting of in situ cement
      mantle.
AB  - During cemented joint arthroplasties, it is necessary to monitor the hardening of
      the cement to know when it is soft enough to allow insertion of the prosthesis
      but viscous enough to maintain bone interlock. Most often, a small piece of
      cement is left out and checked for hardening. These cement pieces are exposed to
      different fates, which include being held in the hand, held between fingers and
      kneaded, and left on the instrument table. The value of any of these techniques
      for predicting the cement's hardening has not been investigated formally. During
      9 total hip arthroplasties, polymethyl methacrylate bone-cement was used in
      cementing the femoral component. Three 1-cm(3) samples collected from each
      operation site were exposed to the aforementioned 3 different conditions. The
      fingertip-held and kneaded cement specimens most closely predicted the time to
      setting of the cement mantle at the operation site.

PMID- 11307138
TI  - Periprosthetic femoral fractures treated with a long-stem cementless component.
AB  - Periprosthetic femoral fractures can be a difficult management problem. Proximal
      femoral fractures with a loose component are managed best with revision
      arthroplasty. We reviewed the midterm follow-up of 14 proximal femoral fractures
      managed with a long-stem extensively porous-coated femoral component. The average
      follow-up in this series was 8.2 years (minimum, 5.3 years). Fractures were
      treated with open reduction and internal fixation, supplemental cortical strut
      grafting when required, and a canal-filling implant. All fractures achieved union
      with an average time to union of 4 months. There have been no component failures
      requiring revision. Twelve prostheses achieved stable bone ingrowth, 1 component
      showed stable fibrous ingrowth, and 1 component was not stable but was not
      symptomatic enough to warrant revision.

PMID- 11307139
TI  - Total knee arthroplasty in an adult with congenital dislocation of the patella.
AB  - This article reports the use of total knee arthroplasty with release of the
      lateral retinaculum, proximal extensor mechanism realignment, and patellar
      resurfacing as a valid treatment option for adult patients with congenital
      dislocation of the patella who have absence of the femoral sulcus and associated
      osteoarthritis. The patient presented in this case report had improvement of his
      Knee Society knee score and function score from preoperative levels of 8 and 45
      to 77 and 80 postoperatively.

PMID- 11307140
TI  - Paratibial cyst associated with wear debris after total knee arthroplasty.
AB  - We present a case in which a synovial cyst arose from the proximal tibia and
      expanded in the calf of a patient after total knee arthroplasty. A cystogram
      showed a direct communication between the joint cavity and the cyst, apparently
      associated with a screw that penetrated the tibial cortex. Histologic examination
      of the cyst showed an inflammatory reaction, including macrophages, foreign body
      giant cells, and metal and polyethylene particles. To our knowledge, this is the
      first case report illustrating a paraosseous cyst that developed after total knee
      arthroplasty. Wear debris from the total knee prosthesis may have been
      responsible for this unusual cyst.

PMID- 11307141
TI  - Arteriovenous malformation mimicking femoral osteolysis after total hip
      arthroplasty.
AB  - We encountered a case of apparent progressive femoral osteolysis around a well
      fixed cementless implant in a young patient. At the time of revision
      arthroplasty, massive hemorrhaging occurred during exposure and attempted femoral
      component extraction. Urgent packing of the exposed endosteum with polymethyl
      methacrylate controlled the bone bleeding. Emergent angiography confirmed an
      arteriovenous malformation with extensive proximal diaphyseal involvement
      directly at the site of osteolysis. This arteriovenous malformation was treated
      successfully with selective arterial embolization and second-stage resection. In
      retrospect, the index arthroplasty operative note indicated an excessive amount
      of blood loss, and prerevision radiographs showed osteolysis with
      uncharacteristic vascular markings. The presence of an osteolytic lesion in total
      hip arthroplasty should not be assumed to be attributed to polyethylene
      granuloma, and any atypical radiographic features should prompt further
      preoperative investigations.

PMID- 11307142
TI  - Fatal pulmonary embolus after shoulder arthroplasty.
AB  - Pulmonary embolus after upper-extremity surgery is a rare complication of upper
      extremity surgery. A case of a fatal pulmonary embolus after shoulder
      arthroplasty is reported. The embolus originated from a lower-extremity deep
      venous thrombosis. The cause of the deep venous thrombosis and subsequent
      pulmonary embolus was attributed to prolonged immobilization in the perioperative
      period.

PMID- 11307143
TI  - Aggressive granulomatous lesion presenting as tumor in cementless long stem total
      hip arthroplasty.
AB  - We describe a patient with an aggressive granulomatous lesion around a cementless
      total hip prosthesis, which simulated a tumor. The granuloma showed a uniform
      histopathology, which included mononuclear cells and metal wear particles.
      Aggressive granulomatous lesions in replaced hips are a distinct condition,
      different from simple loosening or infection; the lesions may grow rapidly, so
      that revision surgery is indicated soon after diagnosis.

PMID- 11307144
TI  - Expression of p21 predicts PSA failure in locally advanced prostate cancer
      treated by prostatectomy.
AB  - The management of prostate cancer is based on several clinicopathological
      criteria. The ability to determine the tumor's biological potential is one goal
      of tumor markers in order to identify patients who may require more intensive
      treatment strategies. The purpose of our study was to determine if
      p21/(WAF1/CIP1) expression can predict biochemical failure in patients with
      locally advanced prostate cancer treated by radical retropubic prostatectomy
      (RRP). We used immunohistochemistry to analyze patterns of p21 expression in a
      population of 296 patients with locally advanced (pT3) prostate cancer treated by
      RRP. Results were correlated with clinicopathological parameters and time to PSA
      failure. For the entire cohort of 296 patients, after adjustment for prognostic
      factors, p21 expression was associated with an increased risk of PSA failure
      (relative risk [RR] = 1.48) of statistical significance at a median follow-up of
      54.5 months. Other parameters that independently predicted the risk of PSA
      failure included lymph node metastasis and seminal vesicle involvement. Because
      neoadjuvant hormonal therapy (NHT) is known to lead to involutional changes in
      prostatic carcinoma, we performed multivariate analyses after stratifying for NHT
      prior to surgery. Among the 172 patients treated by RRP alone, p21 expression was
      an independent predictor of PSA failure (RR = 2.30), as were lymph node
      metastases (RR = 3.19) and pathological grade 5-7 and 8-10 (RR = 2.87 and 3.50,
      respectively). p21 over-expression is an independent predictor of PSA failure in
      pT3 patients treated by radical prostatectomy, especially if they did not receive
      NHT. This tumor marker may help clinicians identify patients who may require
      adjuvant treatment strategies following radical prostatectomy.

PMID- 11307145
TI  - Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese
      population.
AB  - Ser326Cys polymorphism in the hOGG1 gene, which is involved in the repair of 8
      hydroxyguanine in oxidatively damaged DNA, has been identified and the variant
      genotype appears to be related to susceptibility to certain cancers. We
      investigated the association between Ser326Cys polymorphism and squamous-cell
      carcinoma of the esophagus among a Chinese population. hOGG1 gene polymorphism
      was detected by PCR-based single-strand conformation polymorphism and DNA
      sequencing among 201 normal controls and 196 patients with esophageal cancer from
      Linxian, China, a high-risk area for the disease. The association between this
      genetic polymorphism and risk of the cancer was examined by a multivariate
      analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among
      controls (Ser/Ser, 33.8%; Ser/Cys, 52.8%; and Cys/Cys, 13.4%) was significantly
      different from that among esophageal cancer cases (39.8%, 38.8% and 21.4%,
      respectively) (p < 0.05). Homozygosity for the Cys/Cys genotype significantly
      increased the risk of developing esophageal squamous-cell carcinoma, with the
      odds ratio (OR) adjusted for age, sex and smoking being 1.9 (95% confidence
      interval [CI] = 1.3-2.6). Although smoking alone also significantly increased
      esophageal cancer risk in this case-control study (adjusted OR = 2.6; 95% CI =
      1.7-3.9), no significant interaction between smoking and the Cys/Cys genotype was
      observed in terms of risk. Our results suggest that the hOGG1 326Cys allele might
      play a role in the carcinogenesis of the esophagus.

PMID- 11307146
TI  - Differential expression of somatostatin receptors in ependymoma: implications for
      diagnosis.
AB  - Somatostatin receptors (SSts) have been found in a variety of brain tumors, e.g.,
      meningiomas, medulloblastomas and astrocytomas. Our aim was to investigate their
      expression in ependymomas. Using RT-PCR, expression of mRNA for the different SSt
      subtypes was analyzed and quantified in 28 ependymomas and correlated with
      different variables (age, tumor location, histological grade, recurrence and
      survival). In addition, in 8 cases, protein expression was studied in vitro,
      using immunohistochemistry, and in vivo, by somatostatin scintigraphy. mRNAs for
      all 5 subtypes were variably expressed in each ependymoma. The Southern blotting
      signal obtained after SSt(1) and SSt(2) amplification was higher than that for
      the other receptor subtypes. No significant correlation was seen between the
      level of SSt(1) and SSt(2) mRNA expression and age, location, histological
      grading, recurrence or survival. In the 8 cases, SSt(1) staining was negative in
      3 and low in 5. Staining for SSt(2A) was positive but low in every specimen
      analyzed. SSt(1) and SSt(2) immunoreactivity was seen only in the cytoplasm of
      tumoral cells. Somatostatin scintigraphy showed clear uptake, which agreed with
      MRI data in the majority of cases. However, no correlation was seen between
      tracer uptake intensity and histological grade, SSt(1) and SSt(2) mRNA expression
      or immunostaining intensity. This evidence for the expression of SSt(2) receptors
      in ependymomas opens interesting prospects for their follow-up.

PMID- 11307147
TI  - Polymorphisms of glutathione-S-transferase genes (GSTP1, GSTM1 and GSTT1) and
      prostate-cancer risk.
AB  - Several polymorphic glutathione-S-transferase (GST) enzymes are involved in the
      metabolism of a number of potential prostate carcinogens and are thought to
      engage in the transport of steroid hormones. A case-control study was conducted
      to determine the association of the GSTP1, GSTM1 and GSTT1 polymorphisms and
      prostate-cancer risk. The study population consisted of 166 patients with
      previously untreated, histologically proven prostate cancer and 166 age-matched
      control patients with benign prostatic hyperplasia (BPH), all of them Caucasians.
      In the GSTP1 gene, 2 polymorphic alleles, GSTP1*B and GSTP1*C, have been
      described in addition to the wild-type allele, GSTP1*A. Both polymorphic GSTP1
      alleles have an A-to-G transition in exon 5, causing an isoleucine-to-valine
      change. The GSTP1*C allele has an additional transition from C to T. For GSTM1 as
      well as GSTT1, the polymorphic allele is a deletion of the gene. The proportion
      of individuals homozygous for the GSTP1 variant alleles (GSTP1*B/*B, GSTP1*B/*C
      and GSTP1*C/*C) was significantly lower in prostate-cancer patients (4.8%) than
      in BPH controls (14.5%), and the odds ratio (OR) was 0.24 [95% confidence
      interval (CI) = 0.09-0.61). The heterozygous genotypes (GSTP1*A/*B and
      GSTP1*A/*C) were also lower in the cancer group, though this was not significant.
      On the contrary, no significant effect on prostate-cancer risk was detectable for
      either GSTM1 (OR = 0.86, 95% CI = 0.55-1.36) or GSTT1 (OR = 0.78, 95% CI = 0.43
      1.42). Of the polymorphic GSTs, GSTP1 is the most interesting candidate as a
      biomarker for prostate-cancer risk as we found a 76% reduced risk in men
      homozygous for the polymorphic GSTP1 alleles compared to those with wild-type
      GSTP1.

PMID- 11307148
TI  - Presence of telomerase activity in different musculoskeletal tumor histotypes and
      correlation with aggressiveness.
AB  - Telomerase is a ribonucleoprotein enzyme that maintains the protective structures
      at the ends of eukaryotic chromosomes, called telomeres. Telomerase activity was
      observed and correlated with aggressiveness in different neoplasms such as
      breast, prostate, blood and brain cancers, among others. To investigate whether
      telomerase activity is an index of aggressiveness in bone and soft tissue lesions
      of the extremities, 66 biopsy samples from our tissue bank were studied. These
      samples included 43 high-grade sarcomas, 9 aggressive benign tumors and 14
      totally benign lesions. The samples were collected from patients homogeneously
      treated at the Rizzoli Orthopaedic Institute with a follow-up ranging from 4 to
      11 years (median, 7 years). A non-radioactive polymerase chain reaction-based
      enzyme-linked immunosorbent assay was used for the study. All tumors investigated
      were positive for telomerase activity. Among benign lesions, only 2 aneurysmal
      bone cysts showed higher telomerase activity than the cut-off point, whereas all
      the other benign lesions had lower activity. Our results indicate that high
      levels of telomerase activity in bone and soft tissue lesions correlate with more
      aggressive clinical behavior in patients treated with surgery alone. An
      interesting inverse correlation between telomerase activity and occurrence of
      pulmonary metastasis was detected in osteosarcoma patients treated with
      chemotherapy. A parallel increase of telomerase activity and malignancy was
      observed in the adipose and cartilagineous tissue lesions. Our data suggest that
      telomerase activity could be considered a marker of tumor aggressiveness for bone
      and soft tissue lesions. The results obtained in osteosarcoma samples suggest
      that low levels of telomerase activity may be predictive of the prognosis and
      should influence the therapeutic protocol.

PMID- 11307149
TI  - Determination of microsatellite instability, p53 and K-RAS mutations in hepatic
      metastases from patients with colorectal cancer: relationship with response to 5
      fluorouracil and survival.
AB  - In vitro and clinical studies have suggested that high-frequency microsatellite
      instability (MSI-H) phenotype, p53 and K-ras mutations might influence the
      response to chemotherapy in a variety of tumors, including primary colorectal
      cancers (CRC). Unresectable hepatic metastases from CRC are commonly treated with
      5-fluorouracil (5FU) and folinic acid. Since several new active drugs are now
      used for treating CRC, molecular determinants predictive to response to 5FU would
      thus be crucial for optimizing indications of chemotherapy to those patients. MSI
      H phenotype, p53 and K-ras status were characterized in a prospective study of 56
      patients with CRC metastatic to the liver and treated with 5FU-based
      chemotherapy. The objective response rate after a 3-month treatment was 32.1%.
      The prevalence of p53 mutations, K-ras mutations and MSI-H phenotype was 62.5%,
      30.3% and 1.8%, respectively. No significant association was found between
      response to chemotherapy and p53 mutations (78% mutated tumors in responders vs.
      55% in nonresponders; p = 0.10) and K-ras mutations (39% mutated tumors in
      responders vs. 26% in nonresponders; p = 0.34). Survival was longer for patients
      with p53-mutated metastases than for patients with unresected wild-type p53
      metastases (median survival 15 months vs. 17 months; p = 0.06). The determination
      of the MSI-H phenotype, p53 and K-ras status in hepatic metastases from CRC does
      not discriminate a group of patients that should preferentially benefit from 5FU
      based chemotherapy. The prognosis of patients with treated liver metastases is
      better when p53 is mutated.

PMID- 11307150
TI  - Amplification of the MDM2 gene, but not expression of splice variants of MDM2
      MRNA, is associated with prognosis in soft tissue sarcoma.
AB  - The MDM2 gene encodes a 90-kDa oncoprotein that is overexpressed in several human
      carcinomas, osteosarcomas, gliomas and soft tissue sarcomas (STSs). This
      overexpression is the result of several mechanisms, for example, enhanced
      transcription or translation, gene amplification and alternative splicing. We
      found that 19 of 67 (28.4%) STS specimens contained an amplified MDM2 gene. The
      amplification was more likely to be present in grade 1 tumors than in grade 2 or
      3 tumors (58% of grade 1 tumors vs. 15% of grade 2 or 3 tumors, p = 0.001, chi(2)
      test). Furthermore, patients with tumors that contained an amplified MDM2 gene
      had a survival estimate (87 months) that was longer than that of patients with
      tumors that lacked an amplified gene (40 months; p = 0.02, log-rank test).
      Alternatively and aberrantly spliced MDM2 mRNAs were detected in human STSs by a
      highly sensitive reverse transcription-polymerase chain reaction method. Of 71
      tumor samples, 38 (54%) showed evidence of the spliced forms, which included MDM2
      A, MDM2-B and several variants exclusively expressed in STSs. A common feature of
      all forms was the absence of the MDM2 N-terminal region, which includes the TP53
      binding region. Furthermore, the presence of the spliced forms was associated
      with elevated levels of TP53 (p = 0.01, chi(2) test). Although the presence of
      spliced forms was associated with late-stage tumor phenotypes (p = 0.05, chi(2)
      test), we observed no relationship between the presence of splice variants and
      patient outcome.

PMID- 11307151
TI  - Expression of P27(KIP1) is prognostic and independent of MYCN amplification in
      human neuroblastoma.
AB  - Amplification of the MYCN gene is significantly associated with an unfavorable
      prognosis and rapid progression in human neuroblastoma tumors. One potential
      mechanism by which MYCN may cause these effects is by deregulating cell
      proliferation. Tissue culture experiments support a model in which MYC genes
      stimulate cell cycle progression by antagonizing the function of the cell cycle
      inhibitor p27(kip1). In culture, activation of MYC induces both sequestration of
      p27(kip1) by cyclin D complexes and its subsequent proteolytic degradation. We
      have tested whether this model applies to human neuroblastoma in a retrospective
      study of 100 primary tumor biopsy samples from neuroblastoma patients with a
      documented follow-up. Consistent with this hypothesis, MYCN-amplified tumors
      express high levels of both cyclin A and proliferating cell nuclear antigen, 2
      marker proteins of cell proliferation. Further, expression levels of p27(kip1)
      are of prognostic significance in human neuroblastoma patients. Similar to tissue
      culture systems, p27(kip1) is sequestered by cyclin D complexes in a subset of
      human neuroblastoma samples. Surprisingly, however, expression levels of
      p27(kip1) are prognostic independent of MYCN amplification, and tumors that have
      an amplified MYCN gene do not express elevated levels of D-type cyclins or
      contain significantly lower levels of p27(kip1). Our data do not support a model
      in which regulation of p27(kip1) function is an important mechanism by which
      amplified MYCN deregulates cell proliferation in neuroblastoma.

PMID- 11307152
TI  - Interleukin-10 gene promoter polymorphisms in multiple myeloma.
AB  - Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of
      malignant plasma cells in the bone marrow. It is unclear whether genetic
      background could have an etiological impact on MM or influence the course of the
      disease. Interleukin-10 (IL-10) has been implicated in the growth and
      differentiation of normal B cells, and has also been shown to enhance the
      proliferation of MM cells. To address the putative involvement of IL-10 genetic
      variation in MM, we analyzed previously defined loci for bi-allelic polymorphism
      at position -1082 and two microsatellite loci (IL10.G and IL10.R) in the IL-10
      promoter region. Seventy-three patients with MM, 27 with monoclonal gammopathy of
      undetermined significance, and 109 ethnically matched individuals as controls
      were included in the study. Significantly increased frequencies of the IL10.G
      genotype 136/136 and the IL10.R genotype 112/114, in addition to a decreased
      frequency of the IL10.R genotype 114/116, were found among the MM patients.
      Increased production of IL-10 was detected in the supernatants of
      lipopolysaccharide-stimulated peripheral blood mononuclear cells from MM patients
      who were homozygotes (136/136) and heterozygotes (136/non-136) for the IL10.G
      allele 136, as compared with the other IL10.G genotype carriers (non-136/non
      136). These results suggest that the genetic variation in the IL-10 promoter
      region may play a role in the development of MM.

PMID- 11307153
TI  - Founder BRCA1 and BRCA2 mutations in early-onset French Canadian breast cancer
      cases unselected for family history.
AB  - Recently, founder BRCA1 and BRCA2 mutations were identified in Canadian breast
      cancer and breast-ovarian cancer families of French ancestry. The presence of a
      breast cancer case diagnosed at younger than 36 years of age was strongly
      predictive of the presence of any founder mutation screened. Here we report the
      occurrence of founder BRCA1 and BRCA2 mutations in a series of 61 French Canadian
      women with invasive breast cancer diagnosed at age 40 or younger, unselected for
      family history of breast and ovarian cancer. Germline mutations in BRCA1 (n = 4)
      and BRCA2 (n = 4) were identified in 8 of 61 (13%) cases. All BRCA1 mutations
      were found in invasive ductal carcinomas, the most common histologic type of
      tumor in this series. In contrast, the BRCA2 mutations were found in tumors of
      various histologic types: two ductal carcinomas, a tumor containing both ductal
      and lobular histologic types and an invasive lobular carcinoma. Of the 37 women
      with at least one first-, second- or third-degree relative with breast or ovarian
      cancer and the 24 women with no history of these cancers, 7 (19%) and 1 (4%),
      respectively, were mutation carriers. The seven mutation carriers with a family
      history of cancer had at least one first-, second- or third-degree relative with
      a breast cancer diagnosis at less than 51 years of age. The identification of
      founder BRCA1 and BRCA2 mutations in young-onset breast cancer cases unselected
      for family history can facilitate carrier detection when the expected yield of a
      comprehensive screen may be low.

PMID- 11307154
TI  - Reduced membranous and ectopic cytoplasmic expression of beta -catenin correlate
      with cyclin D1 overexpression and poor prognosis in pancreatic cancer.
AB  - Beta-catenin is a component of the E-cadherin-catenin cell adhesion complex. It
      plays also a role in intracellular signaling and can function as an oncogene when
      it binds to the T-cell factor 4 (Tcf4)-binding site in the promoter region of
      cyclin D1 and transactivates genes after translocation to the nucleus. We
      evaluated the immunohistochemical expression pattern of beta-catenin in
      relationship with cyclin D1 overexpression, tumor grade, clinicopathologic
      parameters and patients' survival in 43 ductal adenocarcinomas of the pancreas
      and 5 normal pancreatic tissues. We were able to show that, both reduced
      membranous beta-catenin expression (25 of 43, 58.1%) and accumulation of beta
      catenin in the cytoplasm (28 of 43, 65.1%) correlated significantly with cyclin
      D1 overexpression (both p < 0.0005). Furthermore, we could show a clear
      correlation between reduced membranous expression and ectopic cytoplasmic
      expression of beta-catenin (p < 0.0005). Among patients with carcinomas showing
      no cytoplasmic expression, the 1-year survival was 86.6% whereas among patients
      with carcinomas showing cytoplasmic expression only 35.7% survived 1 year (p <
      0.01). Co-precipitation experiments revealed reduced beta-catenin bound to the E
      cadherin-catenin complex in pancreatic tumor tissues compared with normal
      pancreatic tissues. These results suggest that beta-catenin may be involved in
      the tumorigenesis of pancreatic cancer and exhibited its effects mainly by the
      transactivation of cyclin D1.

PMID- 11307155
TI  - Up-regulation of thioredoxin and thioredoxin reductase in human malignant pleural
      mesothelioma.
AB  - Thioredoxin (Trx) with a redoxactive dithiol together with NADPH and thioredoxin
      reductase (TrxR) is a major disulfide reductase regulating cellular redox state
      and cell proliferation and possibly contributing to the drug resistance of
      malignant cells. We assessed the Trx system in malignant pleural mesothelioma
      cell lines, in nonmalignant pleural mesothelium and in biopsies of malignant
      pleural mesothelioma. The mRNA and immunoreactive proteins of Trx and cytosolic
      and mitochondrial TrxR were positive in all four human mesothelioma cell lines
      investigated. Six cases of nonmalignant, histologically healthy pleural
      mesothelium showed no Trx or TrxR immunoreactivity, whereas immunohistochemistry
      on 26 biopsies of human malignant pleural mesothelioma showed positive Trx in all
      cases and positive TrxR in 23 (88%) of the cases. Moderate or strong
      immunoreactivity for Trx or TrxR was detected in 85% (22 cases) and 61% (14
      cases) of the mesothelioma cases, respectively. Both Trx and TrxR staining
      patterns were mainly diffuse and cytoplasmic, but in 39% of the mesothelioma
      cases prominent nuclear staining could also be detected. Although staining for
      Trx and TrxR was seen in tumor cells, no significant association could be
      demonstrated between Trx or TrxR expression and tumor cell proliferation or
      apoptosis in the biopsies of mesothelioma. There was no significant association
      between the intensity of Trx or TrxR immunoreactivity and patient survival, which
      may possibly be related to moderate or intense Trx and TrxR reactivity in most of
      the cases. Although the Trx system may have an important role in the drug
      resistance of malignant mesothelioma, these studies also suggest that multiple
      factors contribute to the promotion, cell proliferation and apoptosis of
      malignant mesothelioma cells in vivo.

PMID- 11307156
TI  - Strain-dependent susceptibility to MPTP and MPP(+)-induced parkinsonism is
      determined by glia.
AB  - Parkinson's disease (PD) is a debilitating neurological disorder that strikes
      approximately 2% of people over age 50. Current hypotheses propose that the cause
      of PD is multifactorial, involving environmental agents and genetic
      predisposition. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces
      parkinsonism in many species, including humans and shows strain specificity in
      mice. The mechanism of strain specificity, however, remains unknown. Using novel
      chimeric murine substantia nigra cultures, we demonstrate that sensitivity to
      MPTP is conferred by glia and that it does not involve the MAO-B conversion of
      MPTP to MPP(+). C57Bl/6J dopaminergic neurons exposed to MPP(+) demonstrated a
      39% loss when cultured on C57Bl/6J glia compared with 17% neuron loss when
      cultured on resistant SWR/J glia. Similarly, SWR/J neurons exposed to MPP(+)
      demonstrated a 4% loss when cultured on SWR/J glia, but a 14% loss when cultured
      on sensitive C57Bl/6J glia. The identification of glia as the critical cell type
      in the genesis of experimental Parkinsonism provides a target for the development
      of new anti-parkinsonian therapies.

PMID- 11307157
TI  - New method of purification for establishing primary cultures of ensheathing cells
      from the adult olfactory bulb.
AB  - Ensheathing cells exclusively enfold olfactory axons. The ability of olfactory
      axons to reinnervate the adult mammalian olfactory bulb throughout the lifetime
      of an organism is believed to result from the presence of this unique glial cell
      in the olfactory system. This theory has been substantiated by research
      demonstrating the ability of transplanted ensheathing cells to promote axonal
      regrowth in areas of the central nervous system that are normally nonpermissive.
      A simple method for purifying ensheathing cells resulting in a large yield of
      cells is therefore invaluable for transplantation studies. We have developed such
      a method based on the differing rates of attachment of the various harvested cell
      types. The greatest percentage of cells (70.4%) that attached during the first
      step of the separation was determined to be fibroblasts. The remainder of the
      cells were classified as astrocytes (20.8%) and ensheathing cells (6.8%). The
      percentage of attached astrocytes (67.6%) was greatly increased during the second
      purification step while the percentage of fibroblasts decreased greatly (27.9%)
      and the percentage of ensheathing cells (5.3%) slightly decreased. In the final
      cultures, 93.2 % of the attached cells were ensheathing cells, while astrocytes
      (5.9%) and fibroblasts (1.4%) were only minor components. This simple,
      inexpensive method of purifying ensheathing cells will facilitate their use in
      central nervous system regeneration research.

PMID- 11307158
TI  - Modifications of retinal afferent activity induce changes in astroglial
      plasticity in the hamster circadian clock.
AB  - The circadian clock, located in the suprachiasmatic nucleus (SCN) of the
      hypothalamus in mammals, exhibits astroglial plasticity indicated by GFAP
      expression over the 24-h period. In this study, we evaluated the role of neuronal
      retinal input in the observed changes. Modifications of retinal input, either by
      rearing animals under darkness (DD) or under constant light (LL), or by
      suppressing afferent input (bilateral enucleation), induced drastic changes in
      astroglial plasticity. In enucleated animals, a dramatic decrease in GFAP
      expression was evident in the area of the SCN deprived of retinal projections,
      whereas persistence of a rhythmic variation was in those areas still exhibiting
      GFAP expression. By contrast, no changes in astrocytic plasticity were detected
      in hamsters maintained under LL. These data suggest two fundamental roles for
      astrocytes within the SCN: (1) to regulate and mediate glutamate released by
      retinal terminals throughout the neuronal network to facilitate photic signal
      transmission; (2) to contribute to synchronization between suprachiasmatic
      neurons.

PMID- 11307159
TI  - Reactive microglia in dysmyelination and demyelination.
AB  - The relationship between microglial activation and dysmyelination/demyelination
      was analyzed in a long-lived myelin mutant, the Long Evans shaker (les) rat,
      which exhibits early dysmyelination and a later loss of abnormal myelin sheaths.
      A microglial reaction characterized by progressive morphological transformation
      and increasing cell density was localized exclusively to white matter during
      postnatal 2-4 weeks, suggesting a microglial response to dysmyelination and
      oligodendroglial pathology. A further microglial reaction as marked by microglial
      expression of MHC II and a concomitant expression in the brain and spinal cord of
      mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha),
      and inducible nitric oxide synthase (iNOS) began around 4 weeks when the
      remaining myelin was lost. Ultrastructurally, activated microglia ingested
      numerous myelin figures, suggestive of active phagocytosis. Thus, this study
      indicates that microglial reaction is graded in chronic neurological disorders
      and suggests that MHC II expression marks a functional change of activated
      microglia.

PMID- 11307160
TI  - Expression of the Kruppel-type zinc finger protein rKr2 in the developing nervous
      system.
AB  - Zinc finger transcription factors of the Kruppel-class figure prominently in cell
      fate specification and differentiation in the nervous system. One of the Kruppel
      type genes that was originally cloned from an oligodendrocyte library by virtue
      of its homology with the prototypic Kruppel motif is the rat rKr2 gene (Pott et
      al., 1995). In primary cultures of rat glial cells, the rKr2 protein was only
      present in the oligodendrocyte lineage, predominantly in progenitors. Ninety
      percent of A2B5(+) oligodendrocyte progenitors displayed rKr2 immunoreactivity,
      while most MBP(+) oligodendrocytes lacked detectable rKr2. A similar pattern was
      found in vivo, in which the peak expression of rKr2 in the oligodendrocyte
      lineage of rats coincided with the wave of progenitor proliferation in early
      postnatal life. The subventricular zone, a source of neuronal and glial
      progenitors, displayed intense staining for rKr2 at late embryonic and postnatal
      stages. In the adult, cells within the remnants of this germinal zone continued
      to express rKr2 protein strongly. Some populations of mature neurons also
      displayed rKr2 immunostaining. Astrocytes and microglia were not labeled with the
      polyclonal anti-rKr2 antibody in vitro or in vivo. At all developmental stages,
      the rKr2 protein was localized to the nucleus. The stage-specific expression
      pattern and the subcellular localization of rKr2 recommend a role for this
      Kruppel-type gene in the progression of neural stem cells and in the early
      development of the oligodendrocyte lineage.

PMID- 11307161
TI  - Ischemia-induced neuronal expression of the microglia attracting chemokine
      Secondary Lymphoid-tissue Chemokine (SLC).
AB  - Recently, it has been demonstrated that Secondary Lymphoid-tissue Chemokine (SLC)
      is constitutively expressed in secondary lymphoid organs and controls the homing
      of naive T-cells and mature dendritic cells. By screening cDNA isolated from
      ischemic mouse brain, we found expression of SLC mRNA 6 h up to 4 days after the
      onset of ischemia. In situ hybridization combined with immunohistochemistry
      showed neurons expressing SLC mRNA in the ischemic area of the cortex. SLC mRNA
      expression was also found in cultured neurones after various treatments known to
      induce neuronal death, but not in cultured glial cells. Stimulation with SLC
      induced intracellular calcium transients and chemotaxis in cultured microglia.
      Since mRNA encoding CXCR3, an alternative receptor for SLC, but no CCR7 mRNA was
      found in microglia, we suggest that the effects of SLC on microglia are mediated
      by CXCR3. This assumption was corroborated by cross-desensitization experiments
      using IP-10 as a ligand for CXCR3. The inducible expression of SLC in neurones
      acting on microglia suggests a new and important role of SLC in the neuroimmune
      system. We propose that SLC is part of a neurone-microglia signaling system which
      is related to pathological conditions of the brain like ischemia.

PMID- 11307162
TI  - Rapid astrocyte death induced by transient hypoxia, acidosis, and extracellular
      ion shifts.
AB  - Death of astrocytes requires hours to days in injury models that use hypoxia,
      acidosis, or calcium paradox protocols. These methods do not incorporate the
      shifts in extracellular K(+), Na(+), Cl(-), and Ca(2+) that accompany acute brain
      insults. We studied astrocyte survival after exposure to hypoxic, acidic, ion
      shifted Ringer (HAIR), with respective [Ca(2+)], [K(+)], [Na(+)], [Cl(-)], and
      [HCO(-)(3)] of 0.13, 65, 51, 75, and 13 mM (15% CO(2)/85% N(2), pH 6.6).
      Intracellular pH (pH(i)) was monitored with the fluorescent dye BCECF. Cell death
      was indicated by a steep fall in the pH-insensitive, 440-nm-induced fluorescence
      (F440) and was confirmed by propidium iodide staining. After 15-40-min HAIR
      exposure, reperfusion with standard Ringer caused death of most cultured (and
      acutely dissociated) astrocytes within 20 min. Cell death was not prevented if
      low Ca(2+) was maintained during reperfusion. Survival fell with increased HAIR
      duration, elevated temperature, or absence of external glucose. Comparable
      durations of hypoxia, acidosis, or ion shifts alone did not lead to acute cell
      death, while modest loss was noted when acidosis was paired with either hypoxia
      or ion shifts. Severe cell loss required the triad of hypoxia, acidosis, and ion
      shifts. Intracellular pH was significantly higher in HAIR media, compared with
      solutions of low pH alone or with low pH plus hypoxia. These results indicate
      that astrocytes can be killed rapidly by changes in the extracellular
      microenvironment that occur in settings of traumatic and ischemic brain injury.

PMID- 11307163
TI  - Calcium dependence of rapid astrocyte death induced by transient hypoxia,
      acidosis, and extracellular ion shifts.
AB  - Exposure to hypoxic, acidic, ion-shifted Ringer (HAIR) for 15-40 min has been
      shown to cause rapid astrocyte death upon reperfusion with normal media. The ion
      shifts of the HAIR solution included a rise in extracellular K(+) (e.g.,
      [K(+)](o)) and a fall in [Na(+)](o), [Cl(-)](o), and [Ca(2+)](o), characteristic
      of ischemic-traumatic brain insults. We investigated the ionic basis of the HAIR
      induced injury. After HAIR exposure, reperfusion in 0 Ca(2+)/EGTA media
      completely protected astrocytes. Preincubation of cells in BAPTA-AM ester was
      also protective, indicating that the injury was triggered by Ca(2+) influx during
      reperfusion. Neither nimodipine, CNQX, APV, nor TTX reduced injury. Astrocyte
      death could be blocked by 100 microM Ni(2+) or 100 microM benzamil, suggesting
      involvement of Na(+)-Ca(2+) exchange. KB-R7943, which preferentially inhibits
      reverse Na(+)-Ca(2+) exchange, also protected astrocytes. Elevation of [K(+)](o)
      was not necessary for astrocyte death. However, when [Na(+)](o) was maintained at
      151 mM throughout the HAIR protocol, cell death was markedly reduced. We
      postulate that [Na(+)](o) shifts aid reversal of Na(+)-Ca(2+) exchange by
      favoring cytosolic Na(+) loading. Possible means of astrocytic Na(+) accumulation
      are discussed.

PMID- 11307164
TI  - Differential tissue growth and patterns of cell death in mouse limb autopod
      morphogenesis.
AB  - Programmed cell death (PCD) is considered one of the most important cellular
      processes in the morphogenesis of organs and tissues during animal development.
      Although the embryonic limb has been established as a classic model for the study
      of PCD, detailed studies on this process' contribution to morphogenesis are still
      lacking. In the present work, using modern computer-aided techniques, we
      estimated the contribution of PCD to mouse limb morphogenesis. For the detection
      of apoptotic cell death, we stained whole embryonic limbs with acridine orange
      or, in some instances, used the TUNEL technique, and visualized the tissues by
      confocal laser scanning microscopy. We found that cell death patterns are dynamic
      during limb development, and occur in gradients oriented with the main limb axes,
      anteroposterior, dorsoventral and distoproximal. Interdigital apoptosis in the
      autopod was initially detected at the most distal region, and then more
      proximally as development proceeded. Interestingly, we found that digit
      separation is more pronounced on the dorsal side, contrary to what is expected
      from the apoptotic cell distribution, which shows more abundant cell death in the
      ventral region. Using 2-D and 3-D models, we found that most digit
      individualization occurs rather by digit growth than by interdigital cell death.
      Therefore, digits do not mainly individualize by degeneration of preformed
      interdigital tissue, but probably by a dynamic balance between proliferation and
      cell death, reducing interdigital growth, which results in protrusion of digits.
      We determined the expression pattern of fgf-8 during the period of digit
      individualization, as the product of this gene could participate in defining the
      limb growth pattern. Initially, fgf-8 expression was coincident with the apical
      ectodermal ridge, but when cell death was first detected in the interdigits, fgf
      8 expression became restricted to the tip of the growing digits. Therefore, FGF-8
      could be one of the factors responsible for differential digit-interdigit growth,
      and might also act as a survival factor on interdigital tissue. We also found
      that the expression patterns of rar-beta, bmp-2, bmp-4, bmp-7, msx-1, and msx-2
      genes, proposed to be involved in the activation of interdigital cell death, did
      not overlap with, or were not highly expressed in the major zones of cell death
      in the developing limb.

PMID- 11307165
TI  - Type IIA procollagen: expression in developing chicken limb cartilage and human
      osteoarthritic articular cartilage.
AB  - Type IIA procollagen is an alternatively spliced product of the type II collagen
      gene and uniquely contains the cysteine (cys)-rich globular domain in its amino
      (N)-propeptide. To understand the function of type IIA procollagen in cartilage
      development under normal and pathologic conditions, the detailed expression
      pattern of type IIA procollagen was determined in progressive stages of
      development in embryonic chicken limb cartilages (days 5-19) and in human adult
      articular cartilage. Utilizing the antibodies specific for the cys-rich domain of
      the type IIA procollagen N-propeptide, we localized type IIA procollagen in the
      pericellular and interterritorial matrix of condensing pre-chondrogenic
      mesenchyme (day 5) and early cartilage (days 7-9). The intensity of
      immunostaining was gradually lost with cartilage development, and staining became
      restricted to the inner layer of perichondrium and the articular cap (day 12).
      Later in development, type IIA procollagen was re-expressed at the onset of
      cartilage hypertrophy (day 19). Different from type X collagen, which is
      expressed throughout hypertrophic cartilage, type IIA procollagen expression was
      transient and restricted to the zone of early hypertrophy. Immunoelectron
      microscopic and immunoblot analyses showed that a significant amount of the type
      IIA procollagen N-propeptide, but not the carboxyl (C)-propeptide, was retained
      in matrix collagen fibrils of embryonic limb cartilage. This suggests that the
      type IIA procollagen N-propeptide plays previously unrecognized roles in
      fibrillogenesis and chondrogenesis. We did not detect type IIA procollagen in
      healthy human adult articular cartilage. Expression of type IIA procollagen,
      together with that of type X collagen, was activated by articular chondrocytes in
      the upper zone of moderately and severely affected human osteoarthritic
      cartilage, suggesting that articular chondrocytes, which normally maintain a
      stable phenotype, undergo hypertrophic changes in osteoarthritic cartilage. Based
      on our data, we propose that type IIA procollagen plays a significant role in
      chondrocyte differentiation and hypertrophy during normal cartilage development
      as well as in the pathogenesis of osteoarthritis.

PMID- 11307166
TI  - Enhanced expression and stable transmission of transgenes flanked by inverted
      terminal repeats from adeno-associated virus in zebrafish.
AB  - Mosaic expression of transgenes in the F0 generation severely hinders the study
      of transient expression in transgenic fish. To avoid mosaicism, enhanced green
      fluorescent protein (EGFP) gene cassettes were constructed and introduced into
      one-celled zebrafish embryos. These EGFP gene cassettes were flanked by inverted
      terminal repeats (ITRs) from adeno-associated virus (AAV) and driven by zebrafish
      alpha-actin (palpha-actin-EGFP-ITR) or medaka beta-actin promoters (pbeta-actin
      EGFP-ITR). EGFP was expressed specifically and uniformly in the skeletal muscle
      of 56% +/- 8% of the palpha-actin-EGFP-ITR-injected survivors and in the entire
      body of 1.3% +/- 0.8% of the pbeta-actin-EGFP-ITR-injected survivors. Uniform
      transient expression never occurred in zebrafish embryos injected with EGFP genes
      that were not flanked by AAV-ITRs. In the F0 generation, uniformly distributed
      EGFP could mimic the stable expression in transgenic lines early in development.
      We established five transgenic lines derived from palpha-actin-EGFP-ITR-injected
      embryos crossed with wild-type fish and 11 transgenic lines derived from pbeta
      actin-EGFP-ITR-injected embryos crossed with wild-type fish. None of these
      transgenic lines failed to express the transgene, a result confirmed by
      polymerase chain reaction analysis. Stable mendelian transmission of the
      transgenes was achieved in both alpha-actin and beta-actin transgenic lines
      without changing the patterns of expression and integration. Progeny inheritance
      test and Southern blot analysis results strongly suggest that transgenes flanked
      by AAV-ITRs were integrated randomly into the genome at a single locus with a
      concatamerized multiplier. Thus, incorporating AAV-ITRs into transgenes results
      in uniform gene expression in the F0 generation and stable transmission of
      transgenes in zebrafish.

PMID- 11307168
TI  - Type IIA procollagen in development of the human intervertebral disc: regulated
      expression of the NH(2)-propeptide by enzymic processing reveals a unique
      developmental pathway.
AB  - Type II collagen can be synthesized in two forms generated by alternative
      splicing of the precursor mRNA. Type IIA procollagen, which contains a cysteine
      rich domain in the NH(2)-propeptide (exon 2), is produced by precartilage and
      noncartilage epithelial and mesenchymal cells, and type IIB procollagen, without
      the cysteine-rich domain, is characteristic of chondrocytes. Mice lacking type II
      collagen fail to develop intervertebral discs. We have previously shown that the
      human intervertebral disc and notochord synthesize primarily the type IIA form of
      procollagen. Therefore, we investigated the distribution of type IIA procollagen
      during early disc development in humans. By processes of radioactive in situ
      hybridization and fluorescence immunohistochemistry, we localized mRNA and
      protein of type IIA procollagen, type I collagen, and type III collagen in fetal
      intervertebral disc specimens ranging from day 42 (embryonic stage 17) to day 101
      (week 14.5) of gestation. Antibodies to the three distinct domains of type IIA
      procollagen: the NH(2)-propeptide, the fibrillar domain, and the COOH-propeptide
      were used. The earliest stage of developing intervertebral disc (42 days, stage
      17) was characterized by diffuse synthesis of types I and III collagens in the
      dense zone (intervertebral area) and synthesis of type IIA procollagen by the
      chondrocyte progenitor cells surrounding the disc. The notochord cells
      synthesized and deposited into the notochordal sheath all three fibrillar
      collagens. By 54 days (stage 22), the developing disc was clearly divided into
      three regions: 1.) the outer annulus, characterized by synthesis and deposition
      of types I and III collagens; 2.) the inner annulus, characterized by synthesis
      and deposition of type IIA collagen containing the NH(2)-propeptide but devoid of
      the COOH-propeptide (pN-procollagen); and 3.) the notochord, the cells of which
      synthesized and deposited of all three fibrillar collagens. In later stages of
      fetal development (72-101 days), a change in type IIA procollagen processing was
      observed in the cells of the inner annulus: even though these cells continued to
      synthesize type IIA procollagen, they deposited into the extracellular matrix
      (ECM) only the processed fibrillar domain, with the NH(2)-propeptide removed.
      This finding indicates that there is a developmentally regulated change in the
      processing of type IIA procollagen NH(2)-propeptide in the cells of the inner
      annulus. This mechanism is in contrast to previously shown developmental
      regulation of the cysteine-rich domain of the NH(2)-propeptide by alternative
      splicing of the precursor mRNA. Although the cells of the inner annulus have been
      identified as chondrocytes, based on their shape and synthesis of characteristic
      ECM components, they appear to represent a distinct developmental pathway
      characterized by their synthesis and differential processing of type IIA
      procollagen. This developmental pattern may prove important for disc
      regeneration.

PMID- 11307167
TI  - Loss of alpha3beta1 integrin function results in an altered differentiation
      program in the mouse submandibular gland.
AB  - Mammalian submandibular gland (SMG) development leads to the establishment of
      highly organized secretory acinar and nonsecretory ductal epithelial cells. The
      ability of maturing salivary epithelial cells to attain their differentiated
      state has been shown to depend, in part, on interactions between extracellular
      matrix (ECM) proteins and their integrin receptors. In a search for key
      regulators of salivary cell lineage, we have studied alpha3beta1 integrin, a
      receptor for the basement membrane protein laminin, by characterizing embryonic
      day 18 (E18) SMGs isolated from mice carrying a targeted mutation in the alpha3
      integrin gene. Transmission electron microscopy studies showed that the mutant
      SMGs exhibited an aberrant differentiation phenotype with defects in the apical
      basal polarity axis and in the basement membrane. Based on immunohistochemistry
      and Western blot analyses, the alpha3beta1-deficient SMGs had altered expression
      and/or localization of several ECM and adhesive molecules, including laminin
      beta1, fibronectin, alpha5 integrin, and E-cadherin. These changes correlated
      with alterations in the activation state of Ras-extracellular signal-regulated
      kinase (ERK), as well as the expression and/or localization of Cdc42 and RhoA,
      two Rho GTPases that regulate the organization of the actin cytoskeleton. We
      conclude that alpha3beta1 is required for normal salivary cell differentiation
      and that its absence affects multiple components of adhesive complexes and their
      associated signalling pathways.

PMID- 11307169
TI  - Comparative localization of Dax-1 and Ad4BP/SF-1 during development of the
      hypothalamic-pituitary-gonadal axis suggests their closely related and distinct
      functions.
AB  - Two nuclear receptors, Ad4BP/SF-1 and Dax-1, are essential regulators for
      development and function of the mammalian reproductive system. Similarity in
      expression sites, such as adrenal glands, gonads, pituitary, and hypothalamus,
      suggests a functional interaction, and the phenotype similarities were manifested
      in Ad4BP/SF-1-deficient mice and in cases of natural human mutations of Dax-1. In
      this study, quantitative reverse transcriptase polymerase chain reaction analyses
      revealed that expression profiles of Dax-1 in embryonic gonads are different
      between the two sexes and also from those of Ad4BP/SF-1. Immunohistochemical
      analyses clarified the spatial and temporal expressions of the Dax-1 protein
      during development of tissues composing the hypothalamic-pituitary-gonadal axis.
      During gonadal development, Dax-1 occurred after Ad4BP/SF-1 exhibiting a sexually
      dimorphic expression pattern at indifferent stages, indicating a possibility of
      Dax-1 involvement in earliest sex differentiation. When cord formation begins in
      the testis at embryonic day 12.5 (E12.5), Dax-1 was expressed strongly in Sertoli
      cells, but its expression level markedly decreased in Sertoli cells and increased
      in interstitial cells between E13.5 and E17.5. In the female, Dax-1 was strongly
      expressed in the entire ovarian primordium from E12.5 until E14.5, and then its
      expression level was decreased and limited to cells near the surface epithelium
      between E17.5 and postnatal day 0 (P0). During postnatal development of the
      testis, the variable staining of Dax-1 in Sertoli cells was detected as early as
      P7 and Dax-1-expressing Leydig cells became rare. In the postnatal ovary, Dax-1
      expression was detected in granulosa cells with variable staining intensity, and
      occasionally in interstitial cells. During pituitary organogenesis, Dax-1 but not
      Ad4BP/SF-1 was expressed in the dorsal part of Rathke's pouch from E9.5. Later in
      development after E14.5, the distribution of Dax-1 overlapped with that of
      Ad4BP/SF-1, being restricted to gonadotropic cells in the anterior pituitary. In
      the ventromedial hypothalamus (VMH), Dax-1 and Ad4BP/SF-1 were mostly colocalized
      throughout the embryonic and postnatal development. Thus, the coexpression of Dax
      1 and Ad4BP/SF-1 indicates their closely related functions in the development of
      the reproductive system. Furthermore, we noticed the presence of cells that
      express Dax-1 but not Ad4BP/SF-1, further indicating additional functions of Dax
      1 in an Ad4BP/SF-1-independent molecular mechanism.

PMID- 11307170
TI  - Regulation of Epha4 expression in paraxial and lateral plate mesoderm by ectoderm
      derived signals.
AB  - Somitogenesis in all vertebrates involves a mesenchymal to epithelial transition
      of segmental plate cells. Such a transition involves cells altering their
      morphology and their adhesive properties. The Eph family of receptor tyrosine
      kinases has been postulated to regulate cytoskeletal organization. In this study,
      we show that a receptor belonging to this family, EphA4, is expressed in the
      segmental plate in a region where cells are undergoing changes in cell shape as a
      prelude to epithelialization. We have identified the ectoderm covering the
      somites and the midline ectoderm as sources of signals capable of inducing EphA4.
      Loss of EphA4 results in cells of irregular morphology and somites fail to form.
      We also show that when somites fail to develop, expression of EphA4 in the
      lateral plate is also lost. We suggest that signaling occurs between the somites
      and the lateral plate mesoderm and provide evidence that retinoic acid is
      involved in this communication.

PMID- 11307171
TI  - Structural and biophysical simulation of angiogenesis and vascular remodeling.
AB  - The purpose of this report is to introduce a new computer model for the
      simulation of microvascular growth and remodeling into arteries and veins that
      imitates angiogenesis and blood flow in real vascular plexuses. A C++ computer
      program was developed based on geometric and biophysical initial and boundary
      conditions. Geometry was defined on a two-dimensional isometric grid by using
      defined sources and drains and elementary bifurcations that were able to
      proliferate or to regress under the influence of random and deterministic
      processes. Biophysics was defined by pressure, flow, and velocity distributions
      in the network by using the nodal-admittance-matrix-method, and accounting for
      hemodynamic peculiarities like Fahraeus-Lindqvist effect and exchange with
      extravascular tissue. The proposed model is the first to simulate interdigitation
      between the terminal branches of arterial and venous trees. This was achieved by
      inclusion of vessel regression and anastomosis in the capillary plexus and by
      remodeling in dependence from hemodynamics. The choice of regulatory properties
      influences the resulting vascular patterns. The model predicts interdigitating
      arteriovenous patterning if shear stress-dependent but not pressure-dependent
      remodeling was applied. By approximating the variability of natural vascular
      patterns, we hope to better understand homogeneity of transport, spatial
      distribution of hemodynamic properties and biomass allocation to the vascular
      wall or blood during development, or during evolution of circulatory systems.

PMID- 11307172
TI  - Isolation and characterization of posteriorly restricted genes in the zebrafish
      gastrula.
AB  - In order to understand anteroposterior axis formation in vertebrates, we have
      used subtractive hybridization to clone genes expressed posteriorly in the
      zebrafish gastrula-stage embryo. Here we report the initial characterization of
      eight clones isolated from this screen. We find that all eight genes are
      expressed in posteriorly restricted domains, suggesting that they are involved in
      regulating posterior development during zebrafish embryogenesis.

PMID- 11307174
TI  - Hemoglobin variants and determination of glycated hemoglobin (HbA1c).
AB  - Measurement of glycated hemoglobin in diabetic patients is an established
      procedure for evaluating long-term control of diabetes. The Diabetes Control and
      Complications Trial (DCCT), as well as the United Kingdom Prospective Diabetes
      Study (UKPDS), confirmed the direct relationship between the degree of glycemic
      control as estimated by glycohemoglobin (GHb) determinations and the development
      and progression of long-term complications in diabetic patients. Samples with
      known interferences of HbA(1c) determination as hemoglobinopathies are
      specifically excluded from certification testing and there are no guidelines or
      requirements for comparability of samples containing hemoglobin (Hb) variants.
      This paper reviews the interference of Hb variants on determination methods of
      glycated hemoglobin as they result in false HbA(1c) results.

PMID- 11307175
TI  - Diabetes and mass spectrometry.
AB  - Mass spectrometry (MS) has been successfully employed to investigate non
      enzymatic protein glycation, a process relevant in diabetic disease. The high
      sensitivity and specificity of this technique allowed the development of methods
      that can individuate and evaluate some glycation markers to be validly employed
      in monitoring diabetes. More recent mass spectrometric techniques, such as the
      matrix-assisted laser desorption/ionization (MALDI), are able to determine the
      molecular weight of intact proteins. They were first employed in studying the in
      vitro reaction between hexoses and different proteins. Once the validity of the
      results obtained by this analytical approach was confirmed, a series of
      investigations on plasma proteins were undertaken in healthy and diabetic
      subjects. The method led to the evaluation of the number of glucose molecules
      condensed on the protein being studied, and consequently can be validly used for
      an accurate follow-up of metabolic control in diabetic patients. When applied to
      studies on haemoglobin glycation, the method showed that both alpha- and beta
      globins are glycated to a similar extent and that the simply glycated molecules
      are accompanied by glyco-oxidized species therefore giving information on the
      oxidative stress experimented on in the subject. Furthermore, in the case of
      immunoglobulins, MALDI/MS was able to determine not only the total glycation
      level of IgG, but also to establish that the fragment antigen binding (Fab)
      moiety is the most glycated one, thus suggesting that the possible immunological
      impairment sometimes invoked in diabetes is related to the inhibition of the
      process of molecular recognition between antibody and antigen.

PMID- 11307176
TI  - Sensors for glucose monitoring: technical and clinical aspects.
AB  - The aim of this article is to critically discuss the technical and clinical
      aspects of glucose sensors and to briefly review current technical developments.
      This includes sensors for spot glucose measurements as well as those used for
      continuous glucose monitoring. Continuous glucose monitoring in particular should
      supply the diabetic patient with all the information required to optimize insulin
      therapy and metabolic control. Such systems should also allow hypo- and
      hyperglycemic episodes to be avoided. During the last 30 years numerous attempts
      have been made to develop glucose sensors, and new major breakthroughs have been
      announced repeatedly. However, up until now no glucose sensor has been available
      that can be used by diabetic patients in daily life conditions. Also one type of
      glucose sensor, a glucose electrode, recently received approval by the Food and
      Drug Administration (USA) and is commercially available. Other glucose sensors
      employing the transdermal, microdialysis or open tissue microperfusion technique
      are currently under clinical development and may also become available in the
      near future. The types of glucose sensors referred to so far are not truly non
      invasive, but only minimally invasive. They measure glucose concentration in the
      interstitial fluid of the skin or the subcutis. Non-invasive optical glucose
      sensors are designed to monitor glucose changes in the skin by directing light
      through it. They measure the characteristics of the reflected light that are
      changed as the result of an interaction with glucose. However, none of the
      attempts with optical glucose sensors have resulted thus far in the development
      of a sensor that allows monitoring of glucose with sufficient accuracy and
      precision within the clinically relevant glucose range in daily life conditions.
      Nevertheless, more minimal-invasive glucose sensors systems will become available
      for practical use in the near future, whereas it is still uncertain if this can
      be said for any non-invasive glucose sensor.

PMID- 11307177
TI  - Hyperfibrinogenemia and metabolic syndrome in type 2 diabetes: a population-based
      study.
AB  - BACKGROUND: It has been hypothesized that fibrinogen clusters with several
      components of the metabolic syndrome, thus increasing its cardiovascular risk.
      The aims of the present study were to assess in a large population-based cohort
      of patients with type 2 diabetes (1) variables associated with fibrinogen and (2)
      the relationship between hyperfibrinogenemia, a number of components of the
      metabolic syndrome, and coronary heart disease (CHD). METHODS: We identified a
      cross-sectional, population-based cohort of 1574 patients with type 2 diabetes
      using multiple sources of ascertainment. Components of the metabolic syndrome
      were hypertension (systolic blood pressure > or = 160 mmHg and/or diastolic blood
      pressure > or = 95 mmHg and/or treatment with antihypertensive drugs),
      dyslipidemia (tryglicerides >2.82 mmol/l and/or HDL-cholesterol <1.03 mmol/l),
      hyperuricemia (uric acid >416 micromol/l) and increased albumin excretion rate
      (AER > or = 20 microg/min). RESULTS: Fibrinogen increases with age, HbA(1c),
      smoking, hypertension and a number of components of the metabolic syndrome, even
      after adjustment for confounders. Prevalence of CHD increases linearly across
      quartiles of fibrinogen (from 26.1 to 40.6%, p=0.046). However, in logistic
      regression, after adjustment for both confounders and known risk factors for CHD,
      the role of fibrinogen is no more significant, whereas ORs for HbA(1c) between
      6.8 and 8.8% and >8.8% vs values <6.8% are, respectively, 1.91 (95% CI 1.36-2.69)
      and 1.56 (1.07-2.27). CONCLUSIONS: This population-based study shows that
      fibrinogen increases with age, HbA(1c), smoking, hypertension and a number of
      components of the metabolic syndrome, independent of major confounders. We also
      found that poor blood glucose control was associated with CHD.

PMID- 11307178
TI  - Treatment with antioxidants at onset of type 1 diabetes in children: a
      randomized, double-blind placebo-controlled study.
AB  - BACKGROUND: In recent years different types of immune interventions have been
      tried at the onset of type 1 diabetes. Although some have shown effects, none
      have proven to be sufficiently effective to justify the inherent risks and side
      effects. Antioxidants have no or minimal side effects. If they can protect the
      beta cells against free oxygen radicals during the inflammatory process this
      would be a safe and cheap intervention. To evaluate this hypothesis a combination
      of various antioxidative agents was employed in a double-blind randomized study.
      METHODS: The study group comprised 46 children aged 1-17 years at diagnosis. They
      were followed for 3 years: 2 years whilst taking the tablets and 1 year of follow
      up. Twenty-four children were randomly allocated to active treatment with high
      doses of antioxidants and 22 children to placebo tablets. The tablets were the
      same size and tasted identical. RESULTS: Twenty patients had for more than 1
      month an insulin dose <0.5 U/kg in parallel with a normal HbA(1c) value and
      stable blood glucose values, but with no difference observed between those with
      and without active treatment. Nor was any significant difference observed
      regarding C-peptide values, fasting as well as stimulated. Whilst the
      antioxidants demonstrated no positive effect, they also had no negative side
      effects. CONCLUSION: At diagnosis of type 1 diabetes in children, high doses of
      antioxidative agents have no effect either on the preservation of beta cell
      function or on metabolic balance.

PMID- 11307179
TI  - Insulin secretion, obesity, and potential behavioral influences: results from the
      Insulin Resistance Atherosclerosis Study (IRAS).
AB  - BACKGROUND: This work was conducted to evaluate associations of insulin secretion
      with overall and central obesity, dietary fats, physical activity, and alcohol.
      METHODS: A frequently sampled intravenous glucose tolerance test (FSIGT) was used
      to assess acute insulin response to glucose (AIR) and insulin sensitivity (S(I))
      among adult participants (n=675 with normal, NGT; n=332 with impaired glucose
      tolerance, IGT) in the Insulin Resistance Atherosclerosis Study (IRAS).
      Disposition index (DI) was calculated as the sum of the log-transformed AIR and
      S(I) to reflect pancreatic compensation for insulin resistance. Obesity was
      measured as body mass index (kg/m(2), BMI) and central fat distribution by waist
      circumference (cm). Dietary fat intake (total, saturated, polyunsaturated, oleic
      acid), physical activity, and alcohol intake were assessed by standardized
      interview. RESULTS: In unadjusted analyses, BMI and waist were each positively
      correlated with AIR among NGTs (r=0.26 and 0.23, respectively; p<0.0001) but
      correlations were weaker among the IGTs (r=0.10, NS; r=0.13, p<0.05 for BMI and
      waist, respectively). BMI and waist were inversely correlated with DI among NGTs
      (r=-0.13 and -0.20, respectively; p<0.0001) and among IGTs (r=-0.20 and -0.19,
      respectively, p<0.0001). Dietary fat variables were positively related, and
      alcohol was inversely related, to AIR among NGTs (p<0.01) but not among IGTs.
      With all factors considered simultaneously in a pooled analysis of IGTs and NGTs,
      waist, but not BMI, was positively associated with AIR (p<0.001) and inversely
      associated with DI (p<0.01). None of the behavioral variables were independently
      related to either outcome. CONCLUSION: Among non-diabetic patients, central
      obesity appears to be related to higher insulin secretion, but to lower capacity
      of the pancreas to respond to the ambient insulin resistance.

PMID- 11307180
TI  - Thymic expression of insulin-related genes in an animal model of autoimmune type
      1 diabetes.
AB  - BACKGROUND: Insulin and multiple other autoantigens have been implicated in the
      pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self
      reactivity specifically oriented against insulin-secreting islet beta-cells
      remains obscure. The primary objective of the present study was to investigate
      the hypothesis that a defect in thymic central T-cell self-tolerance of the
      insulin hormone family could contribute to the pathophysiology of type 1
      diabetes. This hypothesis was investigated in a classic animal model of type 1
      diabetes, the Bio-Breeding (BB) rat. METHODS: The expression of the mammalian
      insulin-related genes (Ins, Igf1 and Igf2) was analysed in the thymus of inbred
      Wistar Furth rats (WF), diabetes-resistant BB (BBDR) and diabetes-prone BB (BBDP)
      rats. RESULTS: RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealed
      that Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and
      5-week-old WF, BBDR and BBDP rats. In contrast, a complete absence of Igf2 mRNA
      was observed in more than 80% of BBDP thymi. The absence of detectable Igf2
      transcripts in the thymus of BBDP rats is tissue-specific, since Igf2 mRNAs were
      detected in all BBDP brains and livers examined. Using a specific
      immunoradiometric assay, the concentration of thymic IGF-2 protein was
      significantly lower in BBDP than in BBDR rats (p<0.01). CONCLUSIONS: The present
      study suggests an association between the emergence of autoimmune diabetes and a
      defect in Igf2 expression in the thymus of BBDP rats. This tissue-specific defect
      in gene expression could contribute both to the lymphopenia of these rats (by
      impaired T-cell development) and the absence of central T-cell self-tolerance of
      the insulin hormone family (by defective negative selection of self-reactive T
      cells).

PMID- 11307181
TI  - Current literature in diabetes.

PMID- 11307182
TI  - Multiple authors: positive or negative consequences?

PMID- 11307183
TI  - Soft to hard tissue movement ratios: orthognathic surgery in a Hispanic
      population.
AB  - Prediction of the movement ratio of soft to hard tissues is an important part of
      an orthodontic and orthognathic treatment plan. Previous studies have shown that
      various ethnic populations have significantly different average cephalometric
      measurements when compared to European-American norms. Therefore, a difference
      may exist in soft to hard tissue movement ratios in different ethnic populations.
      This study was undertaken to create norms for soft to hard tissue movement ratios
      for orthognathic surgery in a Hispanic population. These results were compared to
      previously published data on European-American populations. Presurgical and
      postsurgical cephalographs were traced and analyzed. The data were divided into 3
      groups based on the surgical procedure performed: maxillary surgery alone,
      mandibular surgery alone, and treatment with a combination of maxillary and
      mandibular surgery. The results indicate that differences exist in soft to hard
      tissue ratios between the European-American and Hispanic populations. It is
      important to incorporate ratios for patients of Hispanic descent into a treatment
      planning protocol so that these patients are treated appropriately.

PMID- 11307184
TI  - Three-dimensional virtual reality surgical planning and simulation workbench for
      orthognathic surgery.
AB  - A new integrated computer system, the 3-dimensional (3D) virtual reality surgical
      planning and simulation workbench for orthognathic surgery (VRSP), is presented.
      Five major functions are implemented in this system: post-processing and
      reconstruction of computed tomographic (CT) data, transformation of 3D unique
      coordinate system geometry, generation of 3D color facial soft tissue models,
      virtual surgical planning and simulation, and presurgical prediction of soft
      tissue changes. The basic mensuration functions, such as linear and spatial
      measurements, are also included. The surgical planning and simulation are based
      on 3D CT reconstructions, whereas soft tissue prediction is based on an
      individualized, texture-mapped, color facial soft tissue model. The surgeon
      "enters" the virtual operatory with virtual reality equipment, "holds" a virtual
      scalpel, and "operates" on a virtual patient to accomplish actual surgical
      planning, simulation of the surgical procedure, and prediction of soft tissue
      changes before surgery. As a final result, a quantitative osteotomy-simulated
      bone model and predicted color facial model with photorealistic quality can be
      visualized from any arbitrary viewing point in a personal computer system. This
      system can be installed in any hospital for daily use.

PMID- 11307185
TI  - Introduction of "vario plates" for retention after mandibular distraction
      osteogenesis.
AB  - This report introduces a new removable orthodontic appliance called "vario
      plates" for retention following distraction osteogenesis of the mandible. The
      "vario plates" consist of removable orthodontic appliances in the maxilla and the
      mandible. These are fabricated out of self-curing resin with typical wire
      elements. They are connected with telescoping maxillomandibular guidance rods,
      which have a smoothly variable length, from the maxillary molar region to the
      mandibular premolar region on each side. The telescope on both sides is
      adjustable in this length by means of a protrusion nut. Thus, it is possible to
      move the mandible forward an exactly controlled amount. The "vario plates" are in
      function for 24 hours a day in the patient for the first 6 months after
      mandibular distraction osteogenesis and subsequently only at night. The
      application of the plates is demonstrated in a patient with Goldenhar syndrome.
      Application of "vario plates" after distraction osteogenesis makes it possible to
      hold the mandible in a stable position. The combination of maxillofacial surgery
      with distraction osteogenesis and orthodontic treatment and retention leads to an
      improvement in therapy of patients with severe dentofacial anomalies.

PMID- 11307186
TI  - Cephalometric assessment of sagittal jaw base relationship prior to orthognathic
      surgery: the role of anterior cranial base inclination.
AB  - In a cephalometric study, 71 presurgical lateral radiographs of patients
      suffering from malpositions of 1 or both jaws were analyzed to assess the
      influence of cranial base inclination on anteroposterior cephalometric angles.
      Angles SNA and SNB, as well as the angle between sella-nasion (SN) and Frankfort
      horizontal (FH), were measured. To verify the true sagittal position of the jaws,
      SNA and SNB were related to a corrected normal anterior cranial base inclination
      (mSNA, mSNB). Two geometric models were calculated and examined. The application
      of the first and second models for SNA and SNB resulted in different estimations
      of the sagittal jaw position in 46% and 38% of the presented patients,
      respectively. Linear regression analysis demonstrates that FH may not be
      substituted for SN as a reference line in anteroposterior measurements, but
      underlines that a correction with regard to anterior cranial base inclination is
      beneficial. According to the results of the second model, the most valuable
      reference line appears to be located approximately halfway between SN and FH.
      Considering the frequent coincidence of jaw malposition and cranial base
      dysmorphia, cranial base-related cephalometric parameters should be interpreted
      carefully.

PMID- 11307187
TI  - An algorithm for determination of ideal location of interdental osteotomies in
      presurgical orthodontic treatment planning.
AB  - Treatment-planning patients with dentofacial deformities begins with the desired
      final occlusal results in mind. Examination of occlusal models and subsequent
      feasibility model surgery determine whether segmentalization of one or both
      arches is necessary to accomplish the final occlusal scheme desired.
      Segmentalization of the maxilla and/or mandible may be used to resolve transverse
      or arch configuration discrepancies, level occlusal plane(s), correct
      dentoalveolar inclination, and/or remove extraction spaces by osteotomy. With so
      many variables to consider, it is often difficult even for an experienced
      clinician to systematically evaluate and select the ideal location of interdental
      osteotomies prior to presurgical orthodontics. This manuscript describes an
      algorithmic approach to diagnosis and treatment planning that will assist the
      clinician in determining the most favorable location(s) for interdental
      osteotomy(ies).

PMID- 11307188
TI  - The predictability of inferior medial canthus as a stable external vertical
      reference point in maxillary repositioning surgery.
AB  - The purpose of this study was to investigate the predictability of using the
      inferior medial canthus as a stable external reference point for establishment of
      the vertical dimension in maxillary orthognathic surgery. Ten consecutive
      patients with skeletal Class II malocclusion and open bite who underwent
      orthognathic reconstructive surgery were included in the study. Prediction
      tracings were completed preoperatively and superimposed on an immediate
      postoperative lateral cephalometric radiograph. In 7 patients, the vertical
      positioning of the maxillary incisal edge on the immediate postoperative lateral
      cephalometric radiograph showed no difference from the superimposed preoperative
      prediction tracing. One patient showed 1 mm difference and 2 patients showed 2 mm
      difference from the preoperative prediction tracings. All cases resulted in
      acceptable maxillary incisal exposure relative to upper lip stomion. It is
      concluded that the inferior medial canthus can be used as a reproducible external
      vertical reference for orthognathic surgery when the technique described herein
      is used.

PMID- 11307189
TI  - Long-term dentofacial stability after bimaxillary surgery in skeletal Class III
      open bite patients.
AB  - The purpose of this study was to evaluate long-term dentofacial stability after
      bimaxillary surgery in skeletal Class III open bite patients. Twenty-three
      Japanese adults (5 males, 18 females) were randomly selected as the experimental
      group from the files of Tohoku University Dental Hospital according to the
      following criteria: (1) skeletal Class III malocclusion with anterior open bite,
      (2) simultaneous Le Fort I and sagittal split ramus osteotomies, and (3) complete
      set of cephalograms taken at predetermined intervals until 5 years after
      debonding. Based on the manner of maxillary surgical repositioning, they were
      divided into the following 2 groups: (1) impaction group of 13 subjects (2 males,
      11 females) who had maxillary superior repositioning without rotation of the
      palatal plane, and (2) rotation group of 10 subjects (3 males, 7 females) who had
      maxillary repositioning with clockwise rotation of the palatal plane. These
      patients were compared to a control group of 11 adults (1 male, 10 females) with
      skeletal Class III malocclusion without open bite who underwent bimaxillary
      surgery by the same techniques. Our data showed that overbite stability in the
      rotation group was better than that in the impaction group. This suggests that
      clockwise rotation of the palatal plane, which moves the anterior maxillary
      structures down, is an effective way to produce a reasonably stable correction of
      the anterior open bite. In contrast, superior repositioning of the maxilla that
      significantly rotates the mandible in the closing direction should be applied
      with caution.

PMID- 11307190
TI  - Comparison of microbial composition in the subgingival plaque of adult crowded
      versus non-crowded dental regions.
AB  - It has been reported in the literature that certain species of bacteria
      (periodontopathogens) present in the subgingival plaque are associated with
      destructive periodontal disease. The purpose of this study was to investigate and
      compare the presence and proportional distribution of periodontopathogens in the
      subgingival plaque of adult crowded versus non-crowded dental regions. Thirty
      adult patients with anterior dental crowding were selected from the Orthodontic
      Clinic of the University of Pennsylvania. After orthodontic records were taken
      and the periodontal examination was performed, subgingival plaque samples were
      collected from crowded (experimental) and contralateral non-crowded regions
      (control) of each patient. The presence of 9 periodontopathic species,
      Actinobacillus actinomycetemcomitans, Prevotella intermedia, Eikenella corrodens,
      Campylobacter rectus, Capnocytophaga species, Fusobacterium species,
      Peptostreptococcus micros, Porphyromonas gingivalis, and Bacteroides forsythus,
      was determined using culture and immunofluorescence techniques. The bacterial
      morphotype was also determined by the use of dark-field microscopy. It was found
      that supragingival plaque accumulation in crowded regions was significantly
      greater than in non-crowded regions. Analysis of the bacteria showed that the
      samples from crowded regions consistently contained more species of
      periodontopathogens than the samples from non-crowded regions. Morphologically,
      more spirochetes and motile rods were present in the crowded-region samples. In
      terms of the presence of individual periodontopathogens, Fusobacterium species,
      Capnocytophaga species, C rectus, and P micros were significantly more common in
      the crowded samples than in the non-crowded samples. It was concluded that: (1)
      more plaque accumulated in crowded areas; (2) more species of periodontopathogens
      were present in the subgingival plaque of crowded regions; (3) morphologically,
      more spirochetes and motile rods were present in crowded areas; and (4)
      Fusobacterium species, Capnocytophaga species, C rectus, and P micros were
      present more often in crowded areas than in non-crowded areas (P < 0.05).

PMID- 11307191
TI  - Simple but effective--the Rickanator.

PMID- 11307192
TI  - Rational and philosophic basis for a functional approach to TMJ fractures in
      children.
AB  - Craniofacial injuries can cause future disturbances of dentofacial development in
      children and youths: their treatment is very important to prevent and minimize
      the consequences on face development. A case of a bilateral condylar fracture is
      reported. Problems connected with clinical management are discussed.

PMID- 11307194
TI  - Second molar replacement therapy made easy with the Viazis bracket.

PMID- 11307193
TI  - The use of surface electromyography in objective measurement of the muscle
      function in facial pain/temporomandibular dysfunction patients.

PMID- 11307195
TI  - Insurance frustration--what can be done?

PMID- 11307196
TI  - Osteogenesis imperfecta and orthognathic surgery: case report with long-term
      follow-up.
AB  - Osteogenesis imperfecta (OI) is the product of the abnormal synthesis and/or
      production of Type I collagen. Successful surgical management of extremity and
      spinal skeletal problems secondary to OI is documented in the orthopedic
      literature. Reports of successful facial skeletal surgery in all types of OI are
      encouraging. The purpose of this paper is to report on the long-term results of
      an orthognathic surgery patient successfully treated to correct a severe
      dentofacial deformity. The patient underwent an uncomplicated Le Fort I osteotomy
      with homologous interpositional bone grafts to advance and inferiorly reposition
      the maxilla. Clinically, the patient appeared to heal without difficulty, and a
      stable Class I skeletal and dental relationship was achieved. Nine years after
      surgery, the patient has a Class I occlusion, with maintenance of his facial
      height and skeletal relationship. Craniomaxillofacial surgery can be predictably
      performed in patients with OI as long as the surgeon maintains strict adherence
      to proper surgical technique and bears in mind the deficiencies of bone density
      and other possible medical complications.

PMID- 11307197
TI  - Obstructive sleep apnea (OSA): a cephalometric analysis of severe and non-severe
      OSA patients. Part II: A predictive discriminant function analysis.
AB  - One hundred male obstructive sleep apnea (OSA) patients were classified into 2
      groups on the basis of apnea-hypopnea index (AHI) as severe (AHI > or = 50) and
      non-severe (AHI < 50). A comprehensive cephalometric analysis of
      cervicocraniofacial skeletal and upper airway soft tissue morphology was
      performed in 51 non-severe and 49 severe OSA patients. In addition, a
      multivariate statistical method (principal component, analysis and predictive
      discriminant analysis) was performed to identify the components that could
      correctly differentiate the severe from the non-severe OSA patients. Eight
      principal components (PCs) of cervicocraniofacial skeletal morphology, 4 PCs of
      hyoid bone position and head posture, and 7 PCs of upper airway soft tissue
      morphology, together with the selected demographic variables, were deduced to
      formulate a linear canonical discriminant function. The equation of a 9-variable
      model was generated as follows: PDF score = 4.127 - 0.144 (Body Mass Index) -
      0.376 (PC1.1) + 0.311 (PC1.4) + 0.214 (PC1.5) + 0.075 (PC 2.1) - 1.309 (PC2.3) +
      0.708 (PC3.2) - 0.059 (PC3.3) + 0.609 (PC3.6). The cutoff score was -0.03899. The
      overall rate of correct classification was 83%. The results showed that Body Mass
      Index and 8 other PCs contributed significantly to the OSA severity. These
      analyses are proven to be a useful adjunctive diagnostic tool to select optimal
      treatment regimens for OSA patients with varying degrees of severity.

PMID- 11307198
TI  - Irreversible alteration in occlusion caused by a mandibular advancement
      appliance: an unexpected complication of sleep apnea treatment.
AB  - A 56-year-old woman who had suffered from socially disturbing snoring, daytime
      tiredness, and panic-like apnea episodes showed mild obstructive apnea in
      somnography. She was examined in the Oral and Maxillofacial Unit of Vaasa Central
      Hospital, Finland. She did not wish to have her malocclusion and lower airway
      obstruction corrected with orthognathic surgery, but instead chose to be treated
      with a mandibular advancement appliance. After having used the appliance nightly
      for more than 3 years, an irreversible alteration in her occlusion was noticed.
      The case is presented and possible reasons for this change are discussed.

PMID- 11307199
TI  - Stability of Le Fort I osteotomy in maxillary inferior repositioning: review of
      the literature.
AB  - Inferior repositioning of the maxilla to correct vertical maxillary deficiency
      has been one of the more unstable orthognathic procedures performed. This kind of
      maxillary movement is the logical correction of short face syndrome due to
      maxillary vertical deficiency, but in spite of the esthetic improvement that it
      produces, a great tendency to relapse was observed. Unfortunately, the procedure
      is relatively rare, and this is reflected in the small sample of the studies. The
      literature concerning the stability of Le Fort I osteotomy in maxillary inferior
      repositioning was reviewed to analyze and discuss the stability of the surgical
      techniques proposed.

PMID- 11307200
TI  - Harmonization of free mandibular movements by orthodontic-surgical treatment of
      patients with mandibular retrognathism.
AB  - The aim of the following study was to investigate whether adult patients with
      mandibular retrognathism combined with a dental Class II relationship without
      craniomandibular pain show a characteristic structure of free mandibular
      movements caused by the neuromuscular system compared to patients with neutral
      skeletal and dental relationships. The authors also analyzed whether these
      characteristic structures changed following orthodontic-surgical treatment. To
      record the spatial movement of the mandible, an ultrasound measurement system was
      chosen and diagnostic software was developed for computer analysis of the
      recorded movements based on physical and biomechanical concepts. Clinically
      complaint-free, adult patients with mandibular retrognathism and distal bite
      exhibited a structure of mandibular movement that was markedly displaced as
      compared to patients with neutral skeletal and dental alignment. After completion
      of orthodontic and surgical treatment, it is apparent that the entire
      neuromuscular system of movement was transformed from one characterized by
      massive dysco-ordination to one of harmonized, coordinated motion, as is seen in
      patients with nonpathologic, neutral relation.

PMID- 11307201
TI  - The effect of ethnicity and age on palatal size and shape: a study in a northern
      Chilean healthy population.
AB  - Race and ethnicity influence the form of the human craniofacial complex in
      varying ways. The aim of the present investigation was to quantify the effects of
      ethnicity (mestizos, Aymara, non-Aymara), age (adolescents and adults), and sex
      on the form (size and shape) of the hard palate in normal Native American
      individuals. From the dental casts of 51 individuals with a complete permanent
      dentition, the x, y, and z coordinates of several standardized palatal landmarks
      were obtained with a computerized 3-dimensional digitizer. Palatal landmarks were
      used to derive a mathematical equation for palatal shape in the frontal and
      sagittal planes. Palatal width and length, frontal and sagittal heights, sagittal
      slope, and deviation of the raphe from the midline were also calculated. In the
      Aymara subjects, there was no effect of sex on palatal size, but there was an
      effect on palatal shape independent of size, especially with respect to male
      growth. Indeed, female palates apparently did not change their shape between
      adolescence and adulthood, while male palates increased their posterior "height."
      Overall, the 3 ethnic groups appeared to possess similar palatal size, with small
      significant differences. In the adult individuals, ethnicity did not seem to
      influence palatal shape. In contrast, adolescent males showed differences: non
      Aymara subjects had the "highest" palatal shape, Aymara the "lowest," and
      mestizos an intermediate position. In conclusion, ethnicity does not seem to be a
      factor of major variability of human hard palate morphology, at least in the
      present 3 northern Chilean groups, as already found for dental arch shape. Age
      probably has a larger effect, particularly in the posterior part of the palate,
      where the eruption of the second and third molars between adolescence and young
      adulthood may play a role. A further development of the present investigation may
      involve larger samples of individuals from different ethnic groups.

PMID- 11307202
TI  - Orthodontic and orthognathic surgical correction of a Class III open bite: a case
      report.
AB  - A significant Class III skeletal discrepancy with open bite and excessive lower
      facial height is presented. The malocclusion was treated with a combination of
      orthodontics and orthognathic surgery.

PMID- 11307203
TI  - An overview of nickel-titanium alloys used in dentistry.
AB  - The nickel-titanium alloy Nitinol has been used in the manufacture of endodontic
      instruments in recent years. Nitinol alloys have greater strength and a lower
      modulus of elasticity compared with stainless steel alloys. The super-elastic
      behaviour of Nitinol wires means that on unloading they return to their original
      shape following deformation. These properties are of interest in endodontology as
      they allow construction of root canal instruments that utilize these favourable
      characteristics to provide an advantage when preparing curved canals. This review
      aims to provide an overview of Nitinol alloys used in dentistry in order for its
      unique characteristics to be appreciated.

PMID- 11307205
TI  - Root canal treatment in general practice in Sudan.
AB  - AIM: The aim of this study was to evaluate the practice and depth of knowledge of
      root canal treatment by dental practitioners in Khartoum, the capital city of
      Sudan, in order to improve the current status of endodontic therapy. METHODOLOGY:
      A questionnaire was posted to 55 registered dental practitioners. Completed
      questionnaires were analysed in term of simple summary statistics. RESULTS: A
      total of fifty-two (95%) practitioners responded. Eighty-five per cent of the
      respondents indicated that they performed root canal treatment for their
      patients. Of these, 84% included molars in their activity. Amongst those who
      carried out root canal treatment, only one practitioner used rubber dam for
      isolation, whilst the remainder used cotton wool rolls. The majority of
      respondents (80%) used hydrogen peroxide to irrigate canals during treatment.
      Three-quarters of practitioners used formocresol as an inter-appointment
      medicament. The stepback preparation technique was the method of choice for 98%
      of respondents. All practitioners used hand instruments to prepare root canals
      and all used gutta-percha for obturation; three-quarters of them used cold
      lateral condensation for all or some cases. The average number of radiographs
      routinely taken for root canal treatment was three. Only 73% used radiographs for
      measuring the working length. Ninety-five per cent of respondents indicated that
      they usually completed a root filling in three or more visits. Three-quarters of
      practitioners restored the teeth permanently immediately after the obturation and
      one-quarter preferred waiting for 1 or 2 weeks. CONCLUSIONS: In Sudan, there are
      no dental practices limited to endodontics and no postgraduate training
      programmes. This survey shows the importance of establishing higher specialist
      training or continuing dental education for practitioners to update their
      knowledge.

PMID- 11307204
TI  - Comparative radiopacity of tetracalcium phosphate and other root-end filling
      materials.
AB  - AIM: This study compared the radiopacity of tetracalcium phosphate (TTCP) and 11
      root-end filling materials relative to human dentine. METHODOLOGY: Specimens of 2
      mm thickness and a graduated aluminium stepwedge were placed on dental X-ray
      films and exposed to an X-ray beam. The optical densities of the specimens and
      aluminium steps were measured. The optical densities of the specimens were
      correlated to the equivalent thickness of aluminium with a regression analysis
      equation. The equation was used to calculate the equivalent aluminium thickness
      of each of the specimens. RESULTS: Nine of the materials were found to be of
      acceptable radiopacity (at least 2 mm Al more radiopaque than dentine). TCCP and
      two of the glass-ionomer compounds were found to have insufficient radiopacity to
      be radiographically distinguishable from human dentine. CONCLUSIONS: All the
      materials were found to be distinguishable radiographically from dentine, except
      for Vitrebond, TTCP and Ketac-Fil. Amalgam was the most radiopaque material and
      Ketac-Fil was the least radiopaque material tested.

PMID- 11307206
TI  - Cleaning efficacy of a new root canal irrigation solution: a preliminary
      evaluation.
AB  - AIM: A new product, electro-chemically activated water, was compared to NaOCl for
      its cleaning effect on root canal walls. METHODOLOGY: Root canal treatment was
      carried out on two groups of extracted teeth with one of the irrigants being used
      in each group. The control group received no treatment. All teeth were split and
      the canal walls viewed in a scanning electron microscope. RESULTS: The canal
      walls of the control group were covered by debris and bacteria. Sodium
      hypochlorite produced clean surfaces with the dentinal tubules open in some areas
      and occluded by the smear layer in other areas; in some areas bacteria were
      visible inside or under the smear layer. Electro-chemically activated water
      produced markedly cleaner surfaces, removing the smear layer in large areas.
      CONCLUSIONS: The cleaning efficacy of electro-chemically activated water in root
      canals was considered to be superior to NaOCl.

PMID- 11307207
TI  - A comparison of thermocouple and infrared thermographic analysis of temperature
      rise on the root surface during the continuous wave of condensation technique.
AB  - AIM: This study was designed to use two methods of temperature measurement to
      analyse and quantify the in vitro root surface temperature changes during the
      initial stage of the continuous wave technique of obturation of 17 single-rooted
      premolar teeth with standard canal preparations. METHODOLOGY: A model was
      designed to allow simultaneous temperature measurement with both thermocouples
      and an infrared thermal imaging system. Two thermocouples were placed on the root
      surface, one coronally and the other near the root apex. A series of thermal
      images were recorded by an infrared thermal imaging camera during the downpack
      procedure. RESULTS: The mean temperature rises on the root surface, as measured
      by the two thermocouples, averaged 13.9 degrees C over the period of study,
      whilst the infrared thermal imaging system measured an average rise of 28.4
      degrees C at the same sites. Temperatures at the more apical point were higher
      than those measured coronally. After the first wave of condensation, the second
      activation of the plugger in the canal prior to its removal always resulted in a
      secondary rise in temperature. The thermal imaging system detected areas of
      greater temperature change distant from the two selected thermocouple sites.
      CONCLUSIONS: The continuous wave technique of obturation may result in high
      temperatures on the external root surface. Infrared thermography is a useful
      device for mapping patterns of temperature change over a large area.

PMID- 11307208
TI  - In vitro evidence that lipopolysaccharide of an oral pathogen leaks from root-end
      filled teeth.
AB  - AIM: The ability to achieve a complete apical seal of the root canal system is
      thought to be important in the success of non-surgical and surgical endodontics.
      The aim of this study was to establish whether or not root-end filled teeth allow
      leakage of lipopolysaccharide (LPS) from a known oral pathogen in vitro.
      METHODOLOGY: Lipopolysaccharide (LPS) from a virulent strain of Prophyromonas
      gingivalis (P. gingivalis) (A7436 from patient with refractory periodontitis),
      was isolated by the Westphall and Jann technique, dialysed extensively,
      lyophilyzed, resuspended in distilled water and analysed by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Root canals from 10 teeth
      were instrumented endodontically and the apical 3 mm of resected roots were
      filled with gutta-percha. The teeth were mounted in 12 mL polypropylene vials by
      using sticky wax and root surfaces were covered with two layers of nail varnish.
      Teeth were filled with 3.3 mg mL-1 LPS and the vials filled with 11 mL of Tris
      Buffered Saline (TBS) containing 0.05% sodium azide. Both positive and negative
      controls were run in parallel with the experimental specimens. Aliquots were
      removed each day and subjected to slot blot analysis to quantitate the amount of
      LPS that had leaked into the bottom of the vials. The density of slots was
      analyzed using a laser densitometer and regression analysis was used to generate
      a standard curve, confidence intervals and experimental values. RESULTS: The data
      indicated that teeth obturated apically with gutta-percha leaked, whilst no LPS
      leakage was detected in teeth covered completely with nail varnish (P < 0.05).
      CONCLUSIONS: In vitro teeth with gutta-percha root-end fills can permit leakage
      of LPS from an identified oral pathogen.

PMID- 11307209
TI  - Sealer distribution in root canals obturated by three techniques.
AB  - AIM: The aim of this study was to observe sealer distribution in root canals
      filled by different root filling techniques. METHODOLOGY: AH26 (0.05 mL) dyed
      with carbon black powder was placed into the prepared root canals of maxillary
      central incisors using a lentulo spiral. Thereafter the canals were obturated
      using three different gutta-percha root-filling techniques. Horizontal sections
      were cut in the apical and middle portions of the filled canals. Images of the
      cross sections were scanned and the percentage of sealer coated canal perimeter
      (PSCP) was measured using a computer digital imaging system. RESULTS: At 3 mm
      from the apex, the PSCP after lateral condensation was similar to that after
      vertical condensation (P > 0.05). At 6 mm from the apex, however, the PSCP was
      significantly higher after lateral condensation than after vertical condensation
      (P < 0.05). At both levels the PSCP was significantly higher after single cone
      (no condensation) than after the other two condensation techniques (P < 0.0001).
      CONCLUSIONS: Sealer may be removed from the canal wall by the condensation
      procedures.

PMID- 11307210
TI  - Canal shapes produced sequentially during instrumentation with Quantec LX rotary
      nickel-titanium instruments: a study in simulated canals.
AB  - AIM: The aim of this study was to determine the shaping ability of Quantec LX
      nickel-titanium rotary instruments in simulated root canals. METHODOLOGY: Forty
      simulated canals consisting of four different shapes in terms of angle and
      position of curvature were prepared with Quantec LX instruments. Sequential still
      images were taken of the canals using a video camera attached to a computer with
      image analysis software. Images were taken preoperatively; after, instrument 7
      (Size 25, 0.05 taper), instrument 8 (size 25, 0.06 taper), and instrument 10
      (size 45, 0.02 taper) were taken to length. Each sequential postoperative image
      was superimposed individually over the preoperative image in order to highlight
      the amount and position of material removed during preparation. Intra-canal
      impressions after preparation to size 10 were taken to evaluate three-dimensional
      canal form. RESULTS: Overall, the mean preparation time to size 10 was 4.7 min;
      canal shape did not have a significant effect on speed of preparation. No
      instruments fractured within the canal, but 7 instruments separated from the
      latch grip, and a further 3 instruments deformed. All canals remained patent.
      Following preparation to size 10, 29 canals (72%) retained their length, 7 (17%)
      lost length, and 4 gained length; the magnitude of the change in length was
      always below 1 mm. Zips were created in 3 canals (7%) after use of size 10
      instruments, but no perforations or danger zones were produced. Excess removal of
      material along the outer aspect of the curve between the beginning of the curve
      and the end-point (outer widening) was found in 22 canals (55%) after instrument
      7, in 30 (75%) canals after size 8 and in 35 canals (88%) after size 10. There
      was a significant difference (P < 0.0001) between canal shapes for the incidence
      of this aberration at all sizes. CONCLUSIONS: Under the conditions of the study,
      Quantec LX instruments tended to remove excess material from the outside of the
      curve between the beginning of the curve and the end-point. These aberrations
      increased in prevalence and severity following the use of larger instruments when
      they were taken to length. Size 8, 9 and 10 Quantec LX instruments should be used
      with care and short of length, especially in severely curved canals.

PMID- 11307212
TI  - A comparison of the relative efficacies of four hand and rotary instrumentation
      techniques during endodontic retreatment.
AB  - AIM: The purpose of this study was to quantify the amount of remaining gutta
      percha/scaler on the walls of root canals when two engine-driven instruments
      (Quantec and ProFile) and two hand instruments (K-file and Hedstrom file) were
      used to remove these materials. The amount of apically extruded debris and the
      time required for treatment were also recorded. METHODOLOGY: One hundred
      extracted mandibular premolars were prepared using a modified step-back, flare
      technique and obturated with the lateral condensation technique. After
      repreparation with the test instruments, the specimens were cut transversally at
      the cervical, middle and apical thirds with steel discs and the three sections
      were split longitudinally. The amount of residual debris on the canal walls in
      each section was examined using a stereomicroscope. RESULTS: In all groups the
      cervical and middle thirds showed no debris. In the apical third, obturating
      material was observed in some specimens. No statistically significant difference
      was found between the two groups for incidence of debris, although the Hedstrom
      group showed a greater number of samples with remaining gutta-percha/sealer. When
      analysing dirty specimens only, there was a statistically significant difference
      between the four groups (P < 0.01) with the Hedstrom group having significantly
      less length of canal wall with remaining obturation material than the Quantec
      group. There was no significant difference amongst the groups for weight of
      extruded debris. However, there was a significant difference amongst the groups
      for mean treatment time with the Hedstrom file group requiring significantly less
      time than the Quantec group (P < 0.001); no significant differences were found
      between the other groups. Six instruments fractured in the Quantec group, four in
      the ProFile group, two in the Hedstrom group and two in the K-type group.
      CONCLUSIONS: The results showed that overall, all instruments may leave filling
      material inside the root canal. During retreatment there is a risk of instrument
      breakage, especially rotary instruments.

PMID- 11307211
TI  - The effect of root canal preparation on microleakage within endodontically
      treated teeth: an in vitro study.
AB  - AIM: The purpose of this study was to evaluate the effects of smear layer and
      canal instrumentation on leakage in root-filled teeth. METHODOLOGY: Six groups (n
      = 12) of freshly extracted human canines and premolars with closed apices and
      single roots were used. Groups A, B, C, and D were instrumented with engine
      driven rotary nickel-titanium MCXIM files and Groups E and F were instrumented
      with conventional stainless steel hand files. Groups A, C, and E were flushed
      with 3.0 mL of 17.0% REDTA to remove the smear layer prior to obturation. All
      teeth were flushed with 5.25% NaOCl, then obturated with AH-26 sealer and either
      the lateral condensation (Groups C-E) or thermomechanical compaction technique
      (Groups A and B). Copper wire was placed coronally in contact with the gutta
      percha in each tooth and, after immersion in 0.9% NaCl solution, a 10 volt dc
      voltage was connected between each tooth and a stainless steel electrode. The
      current flow in the circuit was observed for 45 days. One way ANOVA and Duncan's
      Multiple Range Test were used to compare Groups A-F at time intervals of 10, 20,
      30 and 45 days and identify statistically significant differences. RESULTS:
      Significantly less microleakage occurred when the smear layer was removed and
      when the canals were obturated with thermoplasticized gutta-percha. Canals
      instrumented with engine-driven NiTi files exhibited less leakage than hand
      instrumented canals irrespective of obturation method. CONCLUSIONS: Smear layer
      removal is beneficial to root canal sealing. Obturation with thermoplasticized
      gutta-percha provides a superior seal whilst canal instrumentation with engine
      driven NiTi files reduces the extent of microleakage in root canals.

PMID- 11307213
TI  - Response of Class II molecule-expressing cells and macrophages to cavity
      preparation and restoration with 4-META/MMA-TBB resin.
AB  - AIM: The aim was to test the hypothesis that the resin and bonding agent 4
      META/MMA-TBB (4-META), has the potential to prevent transdentinal antigenic
      challenges. METHODOLOGY: Class I cavity preparation and immediate restoration
      with 4-META were made in the maxillary right first molars of 36 six-week-old
      Wistar rats. Contralateral teeth with an unrestored cavity served as positive
      control (cavity without 4-META) group. The maxillary first molars of 12 age
      matched normal rats (total 24 teeth) were also examined as negative control
      (intact tooth group). At 3 or 28 days after cavity preparation, the teeth were
      subjected to immunoperoxidase staining using OX6 (anticlass II molecules) and ED1
      (antimacrophages) as primary antibodies. RESULTS: A total of 10 teeth were not
      available for histological examination. In the teeth filled with 4-META at 3
      days, the density of OX6+ and ED1+ cells in the coronal pulp was significantly
      higher than that in the intact tooth group. At 28 days, formation of sound
      reparative dentine was noted and the density of the immunocompetent cells was
      comparable to the intact teeth. In the teeth without 4-META at 3 days, pulpal
      abscess was observed in 14 out of 16 and the density of OX6+ and ED1+ cells was
      significantly increased (P < 0.001, paired t-test) compared with the 4-META
      group. Partial pulp necrosis had developed in the teeth without 4-META at 28
      days. CONCLUSIONS: Restoration with 4-META significantly reduced transdentinal
      antigenic challenges. This property may have special implications for 4-META's
      capacity to protect the dentine/pulp complex.

PMID- 11307214
TI  - Detection of a transitional ion concentration zone during electronic measurement
      of root canal length: a study in vitro.
AB  - AIM: The aim of this study was to examine the importance of a transitional ion
      concentration zone at the apical foramen during electronic root canal length
      measurement (ERCLM). METHODOLOGY: The model comprised 21 extracted single-rooted
      human teeth, divided into two experimental groups and one control group, each of
      seven teeth. The anatomical tooth length was determined from the site of
      reference on the tooth crown to the canal orifice and was measured using an
      endodontic file and a vernier caliper. Two aqueous solutions of various NaCl, KCl
      and CaCl2 concentrations were mixed with agar. The Na+, K+ and Ca++
      concentrations corresponded to the average value of each group as determined by
      atomic spectrophotometry evaluation of the extirpated human pulps. The agar
      containing cations was injected into the root canals after their preparation to a
      foramen diameter of 0.70 mm. The control teeth were then completely immersed in
      agar having the same concentration of cations as the agar inside the canal. In
      the first experimental group (group 1), the teeth were immersed in agar so that
      the ion concentration was higher inside the canal; in the second experimental
      group (group 2), the concentrations were reversed. In all three groups, ERCLM was
      performed by an EED 11--resistance type device. Length d1 was defined as the
      length of the root when measured to a value one degree less than the test value.
      Length d2 was defined as the length of the root inducted by the test value, which
      corresponded to the resistance of the periapical agar. RESULTS: In group 1 the
      average d1 length was 0.44 +/- 1.05 shorter than the anatomical foramen (AF), and
      in group 2, 1.11 +/- 0.43 mm longer than AF. In the control group the d1 length
      was on average--3.02 +/- 3.72 mm from the AF. The d1 values of all groups were
      not statistically significantly different from the anatomical length (AL). In all
      three experimental groups the d2 length was statistically significantly different
      from the AL (P < 0.05, t-test); group 1 d2 = AL + 6.32 +/- 1.38 mm; group 2 d2 =
      AL + 6.27 +/- 1.47; control group d2 = AL + 9.15 +/- 1.00 mm. CONCLUSIONS: The
      results of this study indicated that when the electroconductive medium in the
      canal had a different ion concentration than the periapex, and the canal orifice
      had a wide diameter (0.70 mm), the transitional concentration zone influenced the
      accuracy of measurement during ERCLM with a resistance type device. When ion
      concentrations inside and outside the canal were identical, in teeth with a wide
      foramen diameter (0.70 mm or more) the lack of a transitional ion concentration
      zone meant that the length of the root canal could not be determined by ERCLM.

PMID- 11307215
TI  - An in vitro comparison of canal preparation using two automated rotary nickel
      titanium instrumentation techniques.
AB  - AIM: The aim of this study was to compare the efficacy of root canal preparation
      using two automated rotary nickel-titanium instrumentation techniques with a
      double flared balanced forces hand preparation technique, using stainless steel
      files in extracted human teeth. METHODOLOGY: Sixty root canals in extracted human
      teeth were matched for curvature, length and diameter and divided evenly between
      three groups (group 1 = double flare using Flexofiles, group 2 = rotary nickel
      titanium using McXIM instruments and group 3 = rotary nickel-titanium using
      Profile .04 Taper Series 29 instruments). The instruments were used according to
      the manufacturer's instructions in a torque controlled motor and handpiece
      (groups 2 and 3) and according to a predetermined procedure in group 1. A
      standardized radiographic technique using mercury as a contrast medium was used
      to evaluate the canal shape before and after preparation in the plane of maximum
      curvature. The pre- and postoperative radiographic images were compared against
      each other and with a predicted 'ideal preparation' calculated from a projection
      of the final instrument dimensions. The outcome measures were changes in canal
      dimensions as quantified by measuring the changes in the position of the inner
      and outer wall at 1 mm intervals. Alteration in canal curvature could be inferred
      by comparison with the ideal preparation. RESULTS: The degree of canal curvature
      did not influence the effectiveness of any of the techniques. The results showed
      no statistically significant differences in the outcome measures between the
      groups (two-way ANOVA). There were no significant differences in canal wall
      position changes at any level except the apical three, where significantly less
      change occurred in all groups (P = 1%). Instruments fractured in three canals,
      with acute curves in groups 2 and 3. CONCLUSIONS: Canal curvatures were equally
      and well maintained following preparation in all the groups, as long as the
      instrument did not fracture.

PMID- 11307216
TI  - Identification of root canals in molars by tuned-aperture computed tomography.
AB  - AIM: To compare the tuned-aperture computed tomography system of imaging to
      conventional D-speed film for their ability to identify root canals in extracted
      human molars. METHODOLOGY: Thirteen maxillary and six mandibular human molars
      were mounted in acrylic blocks to simulate clinical conditions by surrounding the
      teeth with a radiodense structure. The teeth were then imaged with conventional D
      speed film using a standard paralleling technique, and with a modified
      orthopantomograph OP100 machine using a Schick no. 2 size CCD sensor as the image
      receptor. The source images were registered and TACT slices were generated using
      TACT Workbench Software. Three observers were asked to identify the number of
      canals in the conventional film group and the TACT image group using specific
      criteria. Ground truth was established by cross-sectioning the teeth at the
      coronal, middle, and apical thirds of the roots and directly visualizing the root
      canal morphology. RESULTS: TACT imaging detected 36% of 4th canals in maxillary
      molars and 80% of third canals in mandibular molars. Conventional film detected
      0% of fourth canals in maxillary molars and 0% of third canals in mandibular
      molars. The differences in canal detection between the two techniques were
      statistically significant (Wilcoxon matched pair sign rank test, P = 0.001).
      CONCLUSIONS: In this study, the TACT system of digital imaging was superior to
      conventional film in the detection of root canals in human molars and may be
      useful for the detection of root canals that will probably be missed upon
      conventional X-ray examination.

PMID- 11307218
TI  - Pre- and postsurgical psycho-emotional aspects of the orthognathic surgery
      patient.
AB  - The current study represents an attempt to examine psychologic changes, emotional
      impact, expectations, and satisfaction in patients before and after orthognathic
      surgery. Levels of presurgical anxiety, postsurgical depression, body concept,
      and all the important changes in physiologic functions were measured by 4
      questionnaires, which were self-administered before and after surgery. The
      results of this study suggest that surgery does, in fact, produce improvements in
      self-esteem and body image (patient's evaluation of his or her facial
      attractiveness) and in mastication and speech, and therefore in their lifestyle.
      All patients experienced a medium to high level of presurgical anxiety, but no
      major problems after surgery.

PMID- 11307217
TI  - A 'one-bottle' adhesive system for bonding a fibre post into a root canal: an SEM
      evaluation of the post-resin interface.
AB  - AIM: This report presents a case in which a 'one-bottle' adhesive system was used
      in combination with proprietary resin cement for bonding a fibre post.
      METHODOLOGY: The fibre post was placed into the root canal of a fractured root
      under clinical conditions and then extracted 1 week later. Using scanning
      electron microscopy, half of the root was evaluated for hybrid layer formation
      and the other half for assessing resin tags. RESULTS: The investigation
      demonstrated that a 'one-bottle' system can infiltrate etched dentine.
      CONCLUSIONS: The 'one-bottle' system tested in this study can create a mechanical
      interlocking with root etched dentine under clinical conditions.

PMID- 11307219
TI  - Predictability of bimaxillary orthognathic surgery using "piggyback" intermediate
      splints.
AB  - Ten consecutive patients underwent bimaxillary surgery including segmental Le
      Fort I and bilateral sagittal split ramus osteotomies. All 10 patients were
      symmetric skeletal Class II malocclusion with an anterior open bite. Asymmetry
      cases were excluded. Dimensional changes depicted on the cephalometric prediction
      tracing were reproduced in the model surgery and then transferred to the patient
      during the operative procedure using a "piggyback" intermediate splint. All
      dimensional changes, except vertical, were transferred from the model surgery to
      the patient intraoperatively by using a "piggyback" intermediate splint. The
      accuracy of this transfer and final skeletal result was examined. All the data
      clearly showed that in no case was any discrepancy greater than 2 mm, which
      demonstrates the predictable results that can be achieved by using a "piggyback"
      intermediate splint in bimaxillary orthognathic surgery.

PMID- 11307220
TI  - Skeletal relapse of maxillary osteotomies in unilateral cleft lip and palate
      patients.
AB  - The outcomes of a consecutive series of 10 adults who had unilateral cleft lip
      and palate and who had undergone Le Fort I advancement fixed with miniplates were
      investigated. The amount and timing of horizontal and vertical relapse, the
      correlation between advancement and relapse, and the effectiveness of various
      methods of internal fixation were analyzed with respect to the authors' clinical
      experience and the data from the international literature. Tracings of the
      preoperative and serial postoperative lateral cephalograms--taken immediately and
      during the 1 1/2 to 2 postoperative years--were analyzed to calculate horizontal
      and vertical maxillary change. We found that the use of rigid fixation is
      associated with a significantly more stable postoperative result, as described by
      other authors. Our study suggests that this useful technique does not eliminate
      but reduces and controls the problem of relapse in a series of unilateral cleft
      lip and palate adult patients undergoing Le Fort I osteotomy.

PMID- 11307221
TI  - The Le Fort I downsliding osteotomy: a study of long-term hard tissue stability.
AB  - Surgical maxillary repositioning in individuals with vertical maxillary
      deficiency may be accompanied by skeletal instability. Long-term skeletal changes
      in 13 patients who underwent a Le Fort I downsliding osteotomy were studied
      retrospectively. Nine patients underwent a single-jaw procedure, and 4 patients
      underwent a bimaxillary procedure. Rigid fixation was used in 10 patients, and
      wire osteosynthesis was used in 3. Descriptive statistics, Pearson moment
      correlation, and significance testing were performed at the 5% level. The maxilla
      was stable horizontally over the long term, but it underwent a mean 26.7%
      superior relapse anteriorly. The results were variable, however. Rigid internal
      fixation appeared to enhance the horizontal stability of the maxilla in patients
      who underwent single-jaw surgery. The maxilla was more stable vertically in
      patients who underwent bimaxillary surgery with rigid internal fixation, compared
      to isolated maxillary surgery and rigid internal fixation. The results indicate
      that a 2-mm relapse value may be useful in planning the vertical amount of
      maxillary incisor exposure.

PMID- 11307222
TI  - Pursuing the future while remembering the past.

PMID- 11307223
TI  - Reliability of bimaxillary surgical planning with the 3-D orthognathic surgery
      simulator.
AB  - Functional and esthetic dysgnathia surgery requires accurate planning and precise
      surgical technique. Programs that simulate such surgery have thus become
      increasingly important. These are useless, however, when there is no technique
      for reproduction of surgical planning in the patient. This can be mediated by a
      surgical model. The present study investigates the accuracy resulting from use of
      the 3-D orthognathic surgery simulator (3-D OSS) in reproducing planned patient
      treatment. Eighteen patients with Angle Class III malocclusions who required
      bimaxillary surgery were evaluated. Planning criteria depended on the
      orthognathically intended occlusion and the jaw position simulated in the
      dentofacial planner, which predicted a harmonious profile. Model planning was
      carried out in the 3-D OSS. The accuracy of surgical reproduction was determined
      by cephalometric comparison of the postoperative cephalograms and computer
      simulation images. There were horizontal repositioning errors of 0.61 +/- 0.45 mm
      to 0.78 +/- 0.52 mm at the maxillary reference points (posterior nasal spine,
      anterior nasal spine, point A, and incision superius). Analysis of the
      positioning precision attained vertically was of the same order of magnitude,
      with values between 0.57 +/- 0.46 mm and 0.85 +/- 0.71 mm. Less precision was
      achieved in the mandible. The mean horizontal variation observed at incision
      inferius (0.91 +/- 0.51 mm) was still within the range of values for the maxilla,
      but an increase in the error to 1.61 +/- 0.79 mm was registered caudally to
      menton. The attained position of the maxilla did not vary significantly from the
      planned position (P < or = 0.05). Use of the orthognathic surgery simulator
      allowed precise implementation of the planned surgery. The model planning proved
      to be very helpful in preparing difficult bimaxillary operations.

PMID- 11307224
TI  - An innovative method for accurate positioning of the proximal segment in sagittal
      split osteotomies.
AB  - Ten patients underwent bilateral sagittal split ramus osteotomy for the
      correction of mandibular retrognathia. Prior to the surgery, predictive
      cephalometric tracings were completed, utilizing horizontal and vertical
      reference guides. The anticipated horizontal and vertical changes were determined
      from the predictive tracings, and these results were recorded on the prediction
      tracing. During surgery, corresponding reference marks were made on the lateral
      surface of the mandible. These reference marks were utilized to position the
      proximal segment during surgery, prior to placement of stabilization screws. A
      postoperative lateral cephalometric radiograph was taken within 24 hours in each
      case. The positions of the proximal segments were compared pre- and
      postsurgically. The results of this study indicate that this simple method
      results in accurate positioning of the proximal segments.

PMID- 11307225
TI  - Three-dimensional magnetic resonance imaging of the orbit in craniofacial
      malformations and trauma.
AB  - Craniofacial malformations and trauma often lead to changes in orbital soft
      tissues, requiring surgical correction of both hard and soft tissues. Computed
      tomographic scans and 3-dimensional reconstructions are the optimal tools for
      evaluation of the bony structures. However, there is no equivalent method for the
      orbital soft tissues. The aim of this study was to establish a 3-dimensional
      magnetic resonance imaging (3-D MRI) technique that allows a differentiated
      visualization of the different types of soft tissue in the orbit. A total of 8
      patients with different pathologic conditions of the orbit was examined. Five of
      these patients underwent secondary correction after trauma, and 3 had
      craniofacial malformations. The 3-D reconstruction was performed in the volume
      rendering technique after acquisition of 3-mm axial slices. It was shown that a
      differentiated visualization of the orbital soft tissues is possible. Although
      the thin bony structures have a weak signal and, therefore, the imaging is poor,
      reliable reconstruction of the globe was achieved by different radiologists
      because of its circular delimitation from the bone. This technique is an
      additional support in the planning of orbital surgery.

PMID- 11307226
TI  - Interrelationships between the width, depth, and perimeter of the dental arch.
AB  - Recently, beta function has been shown to be an accurate mathematical model of
      the human dental arch. In this article a beta function-based nomograph is
      presented that shows interrelationships between arch width, arch depth, and arch
      perimeter. This nomograph can be especially useful in predicting the effect of
      orthognathic surgery on these 3 variables of a dental arch.

PMID- 11307227
TI  - Psychosocial predictors of satisfaction among orthognathic surgery patients.
AB  - This study assessed the usefulness of selected psychosocial tests and demographic
      measures in identifying satisfied versus dissatisfied patients who received
      orthognathic surgery. Data were collected prior to placement of orthodontic
      appliances, 1 to 2 weeks presurgery, and at 1 week, 8 weeks, 6 months, 12 months
      and and 2 years postsurgery. The Revised Symptom Checklist-90 (SCL-90-R) scales,
      the Eysenck Personality Inventory (EPI), the Sickness Impact Profile (SIP), and
      the Oral Health Status Questionnaire (OHSQ) were used as independent variables.
      Indicators from the Post-Surgical Patient Satisfaction Questionnaire (PSPSQ),
      which assesses patient satisfaction regarding psychosocial issues, oral
      functioning, and esthetics, served as a postsurgical dependent measure of patient
      satisfaction. Thirty-one male and 86 female subjects participated in the
      multisite randomized trial comparing rigid and wire fixation. Patient age was
      significantly correlated with patient satisfaction from 8 weeks postsurgery
      through 2 years postsurgery. Older patients appear to report greater postsurgical
      satisfaction in comparison to younger patients. The postsurgical OHSQ (esthetics
      subscale) and postsurgical PSPSQ (satisfaction) were significantly related at 8
      weeks, 6 months, 12 months, and 2 years postsurgery. Additionally, PSPSQ
      (satisfaction) and postsurgical OHSQ (general oral health scale) were correlated
      at 12 months. The EPI, SIP, and SCL-90-R were not significantly associated with
      postsurgical satisfaction when assessing the entire study sample. Postsurgical
      qualitative data from the PSPSQ indicated that 50% of the patients reported
      positive outcomes in oral functioning. Sixty-five percent reported esthetic
      improvements, and 37% reported neurosensory loss.

PMID- 11307228
TI  - Fixed implant rehabilitation of the edentulous maxilla: clinical guidelines and
      case reports. Part II.
AB  - Fixed prosthetic implant reconstruction of the edentulous maxilla demands skill
      and state-of-the-art techniques of both the surgeon and the restorative dentist.
      As discussed in Part I (Implant Dent. 1999;8: 186-193), accurate diagnosis and
      treatment planning are essential to successful, predictable clinical results. How
      and where implants are placed have a lasting impact on the quality and prognosis
      of the final restoration. A series of clinical guidelines and considerations is
      reviewed with illustrative clinical treatment protocols of edentulous maxillae of
      unfavorable anatomy including attendant prosthetic difficulties. This article
      addresses the fixed implant rehabilitation of edentulous maxillas with inadequate
      posterior bone and favorable arch position, inadequate posterior bone and
      unfavorable arch position, and inadequate anterior and posterior bone and
      unfavorable arch position.

PMID- 11307229
TI  - Alarms are sounded. Are we listening?

PMID- 11307230
TI  - Effects of xerostomia and the positive advantage of dental implants in these
      patients.

PMID- 11307231
TI  - Marketing the GP/specialist referral system: an opportunity for the future.
AB  - Despite the predictions of some gloom casters, there is a strong economic future
      for dentistry. One of the ways to ensure this strength is to develop an enhanced
      integrated approach to the general practitioner/specialist referral system. This
      requires a planned marketing technique that draws the two practices--GP and
      specialist--into an alliance of greater understanding.

PMID- 11307232
TI  - Histologic analysis of implant sites after grafting with demineralized bone
      matrix putty and sheets.
AB  - Grafting to restore lost alveolar bone is frequently used to enable placement of
      endosseous implants and improve cosmesis. Conflicting reports concerning the
      osteoinductivity of demineralized bone matrix (DBM) and historical use of
      synthetic bone graft substitutes has limited the use of DBM in oral and
      maxillofacial applications. Implant placement after bone grafting provides the
      unique opportunity to biopsy and histologically evaluate new bone formation. Bone
      grafting of the mandible or maxilla was performed to fill extraction sockets and
      restore ridge structures in a consecutive series of eight patients. DBM prepared
      as malleable putty (Grafton DBM Putty) or flexible sheets (Grafton DBM Flex) was
      used. Biopsies were taken at reentry, and histologic analysis determined the
      amount and quality of regenerated bone. Extensive new bone formation and minimal
      residual bone graft matrix were observed at an average of 5 months postoperative.
      The pattern of new bone maturity and remodeling varied by patient and the time in
      situ. Putty and Flex regenerated excellent bone height and width for the
      placement of dental implants, were easy to handle intraoperatively, and readily
      conformed to bony defects.

PMID- 11307233
TI  - Use of hydroxyapatite cement to support implants in extraction sockets.
AB  - Bioactive cements based on calcium phosphate chemistry have been developed to
      serve as bone substitute materials. One such commercial product, BoneSource, is a
      hydroxyapatite cement (HAC) used for small bone defects in the craniofacial
      complex. We have investigated the possibility that HAC could be used to support
      bone growth adjacent to dental implants placed in immediate tooth extraction
      sites. Variable levels of bone contact were noted up to 3 months
      postimplantation. Considerable loss of HAC occurred and was thought to be because
      of "washout" of the cement before complete cement setting. When HAC was immobile
      in the surgical site, the bioactive nature of the cement led to HAC resorption
      and bone deposition. Efforts to maintain the HAC in situ should be expanded so
      that the full clinical potential of the HAC can be realized.

PMID- 11307234
TI  - Three-dimensional finite element analyses of four designs of a high-strength
      silicon nitride implant.
AB  - The effects of implant shape and size on the stress distribution around high
      strength silicon nitride implants under vertical and oblique forces were
      determined using a three-dimensional finite element analysis. Finite element
      models were designed using as a basis the serial sections of the mandible. Using
      Auto-CAD software, the model simulated the placement of implants in the molar
      region of the left mandible. Results of the analyses demonstrated that mainly the
      implant root shape and the directions of bite forces influence the stress
      distributions in the supporting bone around each implant. Implant size is a
      lesser factor. The serrated implants presented a larger surface area to the bone
      than either the cylindrical or tapered implants, which resulted in lower
      compressive stress around the serrated implants. With increasing implant diameter
      and length, compressive stress decreased. The mean compressive stress
      distribution on the serrated implants was more flat (platykurtic) than on either
      the cylindrical or tapered implants. Results of studies on two load directions
      (vertical and oblique) showed that, in either case, the compressive stress in the
      cortical bone around the neck of the implant was higher than in the cancellous
      bone along the length of the implant. The most extreme principal compressive
      stress was found with oblique force. This study provides the first information on
      the relationship between shape of the silicon nitride implant and stress on the
      supporting bone.

PMID- 11307235
TI  - Use of collagen membranes for guided bone regeneration: a review.
AB  - There has been an increase in the use of the resorbable membranes that do not
      require a second stage surgery for removal in guided bone regeneration. The
      purpose of this review is to discuss the immune response of the host to the
      collagen, the use of resorbable membranes derived from Type I collagen of bovine
      Achilles tendon around dental implants, and its potential significance in the
      future of dental implantology.

PMID- 11307236
TI  - Block autografts for localized ridge augmentation: Part II. The posterior
      mandible.
AB  - The posterior edentulous mandible presents unique challenges for implant
      reconstruction because of deficiencies in bone quality and quantity. Autogenous
      mandibular block grafts can be used in a predictable manner to enhance bone
      volume and density, allowing for placement of maximum diameter implants to
      facilitate stress distribution for long-term implant survival. This article will
      feature the importance of staging and recipient site preparation using mandibular
      block autografts for posterior mandibular edentulous reconstruction.

PMID- 11307237
TI  - Use of immediately loaded press-fit cylinder implants in oral reconstruction.
AB  - Press-fit implants can be used to meet the prosthetic needs of patients who
      require immediate loading of their implants. This procedure may be necessary
      because of a patient's unwillingness and/or inability to tolerate a removable
      prosthesis. The implants reported in this study had a similar success rate to
      those immediately loaded screw-type implants previously reported by others. The
      lack of large numbers of long-term immediately loaded implants dictates the need
      for detailed informed consent when using immediately loaded cylinder implants for
      dental reconstruction.

PMID- 11307238
TI  - Inter-implant papilla reconstruction by means of a titanium guide.
AB  - To help reconstruct the osseous support for a missing interdental papilla between
      two adjacent dental implant, an inter-implant papillary template has been
      conceived and fabricated. This titanium housing or stent carries the bone
      grafting mixture to protect the process of osteogenesis during the healing
      period. It eliminates the need for harvesting bone from another area in the oral
      cavity. Because the placement of this titanium component is bone at the first
      stage of surgery (that is, at the implant placement stage), there is no need for
      another surgical invasive procedure. This article describes the shape,
      manipulation, and the handling of the inter-implant papillary template.

PMID- 11307239
TI  - Mandibular flexure and dental implants: a case report.
AB  - The mandibular deformation as a result of jaw movement from rest position has
      been studied and documented by other authors. Here, we report that there is a
      possible correlation between this phenomenon and the discomfort experienced by a
      patient rehabilitated with implant-supported restoration for the mandibular arch
      during function. The recovery from pain and symptoms was achieved only after
      splitting the prosthesis into three sections. This case report serves to remind
      clinicians of the importance of following biological concepts as the key to a
      successful result.

PMID- 11307240
TI  - Fabrication of implant overdentures that are passive and biocompatible.
AB  - Passive-fitting mesostructures and superstructures are required to be
      superimposed on osseointegrated endosseous implants. The tightening of an
      inaccurate framework to the abutments will transmit stresses to the bone-implant
      interface. Precision, until now, has been inconsistent and unpredictable with
      conventional methods of casting, soldering, and welding techniques. By machining
      the framework with the Spark Erosion method using electrodischarge machining, a
      substantial improvement in the passive seat of the prosthetic elements is
      achieved. Chemical reactions caused by galvanic corrosion are also important
      factors in the precise approach to the treatment planning of implant-supported
      prostheses. The application of a pure 11.8% grade 1 titanium casting system
      allows the restorative team to fabricate porcelain-fused-to-metal crowns and
      bridges, conventional fixed-removable restorations and implant prostheses in pure
      titanium within completely biocompatible parameters that are absolutely mercury
      free. This article explains why the spark erosion machining and the unique
      titanium casting system have a significant impact on today's implant dentistry.

PMID- 11307241
TI  - A TMD specialty?

PMID- 11307243
TI  - Radiographic anomalies: are your patient records accurate?

PMID- 11307242
TI  - Second molar extraction therapy--two case reports.
AB  - As in many areas of dentistry, the topic of second molar extraction therapy has
      its followers and its critics. Besides the problem of accurately predicting the
      eruption position of the third molars, I have also been concerned about the
      effect on the cranium and the temporo-mandibular joints. The majority of my
      patients with mild or moderate crowding are treated without extractions. The
      third molars, if present, are kept under observation. There is, however, one
      group of patients that responds well to the loss of second molars and for which,
      in my opinion, any alternative extraction pattern would compromise the patient
      with regard to function and facial appearance. This group is the mild Class III
      skeletal pattern with buccally crowded canines.

PMID- 11307244
TI  - OPAP--a new approach to the management of obstructive sleep apnea.

PMID- 11307245
TI  - Removal of second molars to alleviate crowding and to facilitate orthodontic
      treatment.

PMID- 11307246
TI  - An interview with Dr. Pamela A. Steed. 1997 AAFO Clinician of the Year. Interview
      by Dr. Craig C. Stoner.

PMID- 11307247
TI  - A comparative evaluation of apical linear dye penetration of Glass ionomer based
      sealers with conventional root canal sealers. An in vitro study.
AB  - This study was done to evaluate the clinical practicality of a new Water mixable
      Glass ionomer root canal sealer with conventional type 11a Glass ionomer cement,
      if used as a sealer, along with Zinc oxide Eugenol and Calcium Hydroxide
      containing sealers. Forty freshly extracted single rooted Maxillary incisors were
      selected for the study. Ten teeth were assigned for each sealer group. Access
      cavity was prepared, wording length determined, modified step-back preparation
      and obturation of the root canal done with lateral condensation technique.
      Assigned groups were Group 1--Type 11a Glass ionomer cement, Group 11--Mixed
      Tubliseal, Group 111--Mixed Sealapex, Group IV--Endion. Micro leakage Values were
      assessed by the amount of linear dye penetration in to the apical pulp space.
      Statistical analysis was done with one way analysis (ANOVA), using Fisher's 'F'
      test and students unpaired 't' test. Seal apex exhibited the least micro leakage
      value and found to be the best sealer among the four sealer groups.

PMID- 11307248
TI  - An investigation into the effect of solidification shrinkage on distortion of
      casting and flexure strength of various solders for base metal alloys. A
      laboratory study.
AB  - This study was undertaken to determine the distortion due to solidification
      shrinkage and to evaluate the flexure strength properties of soldered joints
      between combination of three commercially available base metal alloys and
      solders. Ninety rectangular bars were cast using three commercially available
      alloys for soldering (30 bars of each alloys). Ten bars of each alloy were
      soldered using electrical soldering unit and solder recommended by respective
      manufacturers, twenty bars (ten pairs each) were soldered using other solders.
      Length between the references markings on the specimen were measured using a
      vernier caliper and travelling microscope to check the possible solidification
      shrinkage. The specimens were then subjected to flexure strength evaluation using
      a universal testing machine. Statistical comparison of dimensional changes due to
      solidification shrinkage and flexure strength evaluation of soldered joints was
      done using analysis of variance test. Recommended Ni-Cr solders showed less
      shrinkage compared to that of the Co-Cr solders from the tested specimens and
      superior flexure strength was found in Co-Cr alloy specimen (P value P > .001)
      soldered with Co-Cr alloy solders.

PMID- 11307249
TI  - Stress variations in recast Ni-Cr alloy--a finite element analysis.
AB  - A finite element analysis was carried out to analyse the stress variations in a
      mandibular posterior fixed partial denture (FPD), made of recast nickel-chromium
      alloy. A two dimensional finite element model was developed and then analysed
      with STAAD III/ISDS program with an occlusal load of 1 kg applied to the casting
      surface. The analysis revealed that the connectors experienced maximum stresses
      and the generated stress values decreased within the fixed partial denture made
      of recast Ni-Cr alloy. It seemed unlikely that FPD inspite of being made of
      recast alloy might fail before the other tissue components show signs of
      degeneration thus establishing the potential for recycling the Ni-Cr alloy in
      actual dental practice.

PMID- 11307250
TI  - Oral health and treatment needs in institutionalized psychiatric patients in
      India.
AB  - The caries prevalence, oral hygiene status, periodontal health and treatment
      needs were evaluated in a group of institutionalized psychiatric patients in Goa,
      India. Of the total 153 inmates, males constituted 59 percent, the mean age was
      25 years, 96 percent were self sufficient and the response rate was 84 percent.
      63 percent were diagnosed with schizophrenia. They did not receive any assistance
      in daily self-care activities including oral hygiene maintenance. None of the 5
      edentulous patients had dentures, 5% had been referred for emergency dental care
      during the period of institutionalization. 15 subjects (12%) were caries-free,
      the stepwise linear regression analysis showed that the mean DMFT index
      significantly increased with age (t = 2-819, PL 0.05). Two third of the study
      population (88%) were in need of conservative dental treatment. The stepwise
      linear regression analysis showed that the mean OHI-S index significantly
      increased with age (t = 2.412, P < 0.01). Only 5.4% reported a healthy
      periodontium whereas 16.27% required complex periodontal therapy. Soft tissue
      lesions included dorsal lingual depapillation/heavily coated areas and angular
      cheilitis in addition to incidental observations such as mucosal
      hyperpigmentation, gingival hyperplasia, and leucoedema. Bruxism and factitious
      injuries were also noted. The onus of meeting the oral health needs of this
      marginalized patient population therefore depends on the effectiveness of
      community dentistry programs vis a vis the efforts of the staff of the
      institution to provide such services on a regular basis.

PMID- 11307251
TI  - Apical inflammatory root resorption: a correlative radiographic and histological
      assessment.
AB  - AIM: To assess the reliability of routine single radiographs in the diagnosis of
      inflammatory apical root resorption by correlating the radiographic and
      histological findings. METHODOLOGY: The material comprised serial and step serial
      sections of plastic-embedded root-apices with attached apical periodontitis
      lesions that were prepared for a previous study and the diagnostic radiographs.
      The histological sections of 114 specimens were analysed by light microscopy and
      categorized into three groups: (i) those without any resorption (0); (ii) those
      with moderate resorption (+); and (iii) those with severe resorption (+ +). The
      radiographs were examined by a separate examiner and graded with a similar
      categorization of no resorption (0); moderate (+); and severe (+ +) apical
      resorption. RESULTS: Radiographically, 19% of the teeth were diagnosed as having
      apical inflammatory root resorption, whereas histologically, 81% of the teeth
      revealed apical inflammatory root resorption. A correlative radiographic and
      histological assessment (n = 104) revealed a coincidence of diagnosis in 7% of
      the specimens and noncoincidence of diagnosis in 76% of the specimens.
      CONCLUSIONS: The results indicate that routine single radiographs are not
      sufficiently accurate or sensitive to consistently diagnose apical root
      resorptive defects developing as a consequence of apical periodontitis.

PMID- 11307252
TI  - Cleaning effectiveness of root canal irrigation with electrochemically activated
      anolyte and catholyte solutions: a pilot study.
AB  - AIM: The aim of this study was to evaluate the potential of electrochemically
      activated (ECA) anolyte and catholyte solutions to clean root canals during
      conventional root canal preparation. METHODOLOGY: Twenty extracted single-rooted
      human mature permanent teeth were allocated randomly into four groups of five
      teeth. The pulp chambers were accessed and the canals prepared by hand with
      conventional stainless steel endodontic instruments using a double-flared
      technique. One or other of the following irrigants was used during preparation:
      distilled water, 3% NaOCl, anolyte neutral cathodic (ANC) (300 mg L-1 of active
      chlorine), and a combination of anolyte neutral cathodic (ANC) (300 mg L-1 of
      active chlorine) and catholyte. The teeth were split longitudinally and the canal
      walls examined for debris and smear layer by scanning electron microscopy. SEM
      photomicrographs were taken separately in the coronal, middle and apical parts of
      canal at magnification of x800 to evaluate the debridement of extracellular
      matrix and at a magnification of x2500 to evaluate the presence of smear layer.
      RESULTS: Irrigation with distilled water did not remove debris in the apical part
      of canals and left a continuous and firm smear layer overlying compressed low
      mineralized predentine. All chemically active irrigants demonstrated improved
      cleaning potential compared to distilled water. The quality of loose debris
      elimination was similar for NaOCl and the anolyte ANC solution. The combination
      of anolyte ANC and catholyte resulted in improved cleaning, particularly in the
      apical third of canals. The evaluation of smear layer demonstrated that none of
      the irrigants were effective in its total removal; however, chemically active
      irrigants affected its surface and thickness. Compared to NaOCl, the ECA
      solutions left a thinner smear layer with a smoother and more even surface. NaOCl
      enhanced the opening of tubules predominantly in the coronal and middle thirds of
      canals, whereas combination of ANC and catholyte resulted in more numerous open
      dentine tubules throughout the whole length of canals. CONCLUSIONS: Irrigation
      with electrochemically activated solutions cleaned root canal walls and may be an
      alternative to NaOCl in conventional root canal treatment. Further investigation
      of ECA solutions for root canal irrigation is warranted.

PMID- 11307253
TI  - Pulpal response to prolonged dentinal exposure to sodium hypochlorite.
AB  - AIM: The aim of this study was to examine the effect of undiluted NaOCl on vital
      pulp tissue when applied to freshly cut dentine. METHODOLOGY: Class V cavities
      were prepared to a depth of 2 mm in 20 teeth in four Beagle dogs. The cavities on
      one side of each dog were irrigated continuously for 5 min with 5.25% NaOCl,
      whilst the cavities on the opposite side in each dog were irrigated with saline
      for the same length of time. Prior to filling each cavity with Cavit, they were
      again rinsed with saline and gently dried with an air stream. The dogs were
      sacrificed to allow for investigation of pulpal conditions under the cavities
      after periods of 24 h, 1 week, and 4 weeks. Histological preparations were made
      and stained with H & E for evaluation of the pulp subjacent to each cavity. The
      tissues were examined for presence of inflammatory cells and categorized as (i)
      no inflammation, (ii) mild, (iii) moderate, and (iv) severe inflammation.
      RESULTS: The six teeth in the 24 h observation group all showed mild
      inflammation, both in the NaOCl and the saline groups. After 1 week and 4 weeks,
      the pulps from all the teeth were free of inflammatory cells. CONCLUSION: Under
      the conditions of this experiment, the use of NaOCl in a freshly cut cavity in an
      intact tooth of a dog, with exposed dentinal tubules, does not appear to cause
      additional pulpal damage to that caused by the physical contact in cutting tooth
      structure.

PMID- 11307254
TI  - Periapical status and quality of root fillings and coronal restorations in a
      Danish population.
AB  - AIM: The aim of this study was to investigate the quality of endodontic and
      coronal restorations and the association with periapical status in a Danish
      population. METHODOLOGY: A total of 614 randomly selected individuals (20-60+
      years of age) from Aarhus County had a full-mouth radiographic examination. The
      quality of endodontic and coronal restorations and the periapical status of
      endodontically treated teeth were assessed by radiographic criteria. Root
      fillings were categorized as 'adequate' or 'inadequate' with regard to root
      filling length and lateral seal. Coronal restorations were categorized into
      'adequate' and 'inadequate', defined by the absence or presence of radiographic
      signs of overhangs or open margins. Results were analysed statistically using the
      chi-squared test. RESULTS: The total number of endodontically treated teeth was
      773, and 52.3% had apical periodontitis (AP). Root-filled teeth with an adequate
      lateral seal had a lower incidence of AP than teeth with an inadequate seal
      (44.3% vs. 57.8%), and teeth with an adequate root filling length were associated
      with a better periapical status than teeth with inadequate length of the root
      filling (42.0% vs. 67.6%). Similarly, adequate coronal restorations were
      associated with better periapical status than inadequate restorations (48.0% vs.
      63.9%). When both root filling and coronal restoration quality were assessed, the
      incidence of AP ranged from 31.2% (optimal quality) to 78.3% (all parameters
      scored as inadequate). CONCLUSIONS: Inadequate root canal and coronal
      restorations were associated with an increased incidence of AP.

PMID- 11307255
TI  - The standardized-taper root canal preparation--Part 1. Concepts for variably
      tapered shaping instruments.
AB  - AIM: To introduce the concept of variable taper instruments for predictable and
      ergonomic root canal preparation, and demonstrate the design features of Greater
      Taper files. SUMMARY: Optimal root canal shaping is difficult to practice and
      teach with traditional instruments. Instrument sequences are complex, with up to
      18 instruments and 63 procedural stages, providing almost limitless scope for
      poor results and iatrogenic error. In the first of six articles, Dr Buchanan
      describes the Variable Taper concept, which grew from such frustrations, and
      represents a new concept in file design. Milled from NiTi alloys in tapers of
      0.06, 0.08, 0.10 and 0.12 mm mm-1, with accessory files for wide canals, their
      design embodies the key shaping features of adequate coronal enlargement, full
      deep shape, and predictable apical resistance form case after case. The ease and
      simplicity of their use is described, and enhanced cleaning and obturation
      outcomes discussed in relation to their unique design features. KEY LEARNING
      POINTS: Canal preparation is difficult to practice and teach with traditional K
      files and Gates Glidden drills. Variable Taper files are designed to offer the
      optimal preparation features of adequate (not excessive) coronal enlargement,
      full deep shape, and apical resistance form in a simple instrument sequence.
      Variable Taper technique is simple to master, and offers predictable cleaning and
      obturation outcomes, even in inexperienced hands.

PMID- 11307256
TI  - An unusual case of furcation external resorption.
AB  - AIM: To describe the presentation and management of an unusual external root
      resorption. SUMMARY: An unusual external inflammatory root resorption presented
      in the furcation of a mandibular first molar. Review of earlier radiographs
      suggested that the lesion was non-progressive. Occlusal trauma associated with
      anterior open bite was the most likely aetiological factor. No active treatment
      was prescribed. KEY LEARNING POINTS: External resorption may occur following loss
      of the external root surface. Occlusal trauma may be a propagating stimulus for
      progressive resorption. Lesions may sometimes be non-progressive, and treatment
      may therefore be more damaging than observation.

PMID- 11307257
TI  - Effects of endodontic instrument handle diameter on electromyographic activity of
      forearm and hand muscles.
AB  - AIM: To determine the influence of the handle diameter of endodontic instruments
      on forearm and hand muscle activity using electromyographic (EMG) recording.
      METHODOLOGY: Size 45 K-type files were fitted with four different handle
      diameters; 3.5, 4.0, 5.0, and 6.0 mm. Seven dentists then attempted to negotiate
      to the working length acrylic resin root canals with each of the four handle
      sizes using a reaming motion. EMG activities were recorded from the flexor
      pollicis brevis muscle (f.p.b.), the flexor carpi radialis muscle (f.c.r.), and
      the brachioradialis muscle (b) with bipolar surface electrodes. The time taken to
      negotiate the canals, the area of integrated EMG that corresponded to the amount
      of EMG activity required during penetration and the maximum amplitude of EMG were
      measured using the EMG data. Results were analysed statistically using a one-way
      factorial ANOVA test and multiple comparison tests. RESULTS: Reaming time and
      integrated EMG area of each muscle decreased with an increase in handle diameter.
      The most significant difference in time and area of integrated EMG was detected
      between handles of 6 mm and 3.5 mm diameter (time: P < 0.01, area of the f.p.b.:
      P < 0.01, area of the f.c.r. and b: P < 0.05), and between handles of 5 mm and
      3.5 mm diameter (P < 0.05). Both 5 mm and 6 mm handles significantly decreased
      the maximum amplitude of EMG recorded from the f.p.b. compared with 3.5 mm
      handles (between 3.5 mm and 6 mm: P < 0.01, between 3.5 mm and 5 mm: P < 0.05).
      CONCLUSION: The results indicate that handle diameter has an effect on reaming
      time as well as on muscle activity. As a consequence, handle diameter influenced
      operator performance during instrumentation.

PMID- 11307258
TI  - Canal shapes produced sequentially during instrumentation with Quantec SC rotary
      nickel-titanium instruments: a study in simulated canals.
AB  - AIM: The aim of this study was to determine the shaping ability of Quantec SC
      nickel-titanium rotary instruments in simulated root canals. METHODOLOGY: Forty
      simulated canals consisting of four different shapes in terms of angle and
      position of curvature were prepared with Quantec SC instruments. Sequential still
      images were taken of the canals using a video camera attached to a computer with
      image analysis software. Images were taken preoperatively, and then after
      instrument 7 (Size 25, 0.05 taper), instrument 8 (size 25, 0.06 taper), and
      instrument 10 (size 45, 0.02 taper) were taken to length. Each sequential
      postoperative image was superimposed individually over the preoperative image in
      order to highlight the amount and position of material removed during
      preparation. RESULTS: Overall, the mean preparation time to size 10 was 3.6 min
      with 12 mm canals taking on average less time than 8 mm canals. There was a
      highly significant difference between the canal types (P < 0.0001). No
      instruments fractured within the canal or deformed, although one instrument
      separated from the latch grip. All canals remained patent. Following preparation
      to size 10, 19 canals (48%) retained their length, eight (20%) lost length, and
      13 (32%) gained length; the magnitude of the change in length was always 0.5 mm
      or below. Following preparation to size 7 instruments all canals showed aberrant
      shapes. Excess removal of material along the outer aspect of the curve between
      the beginning of the curve and the end-point (outer widening) was found in 26
      canals (65%) after instrument 7. At the same stage of preparation six canals
      (15%) had zips, three (8%) had ledges and five (13%) had perforations. Following
      preparation to size 10, 27 (68%) canals were perforated. CONCLUSIONS: Under the
      conditions of the study, Quantec SC instruments consistently produced aberrations
      when canals were enlarged to size 7 (size 25, 0.05 taper) or above. Care should
      be exercised when using these instruments in real teeth.

PMID- 11307259
TI  - Effect of exposing dentine to sodium hypochlorite and calcium hydroxide on its
      flexural strength and elastic modulus.
AB  - AIM: The aim of this study was to evaluate the effect of sodium hypochlorite
      (NaOCl) solutions (3%, 5%) and saturated calcium hydroxide (Ca(OH)2) solution,
      individually and consecutively, on the flexural strength and modulus of
      elasticity of standardized dentine bars. METHODOLOGY: Standardized plano-parallel
      dentine bars (n = 121) were divided into five test groups and one control group.
      The control group 1 consisted of dentine bars, stored in normal saline until
      testing. The dentine bars in the five test groups were treated by exposure to the
      following solutions; group 2--3% NaOCl, 2 h; group 3--5% NaOCl, 2 h; group 4-
      saturated Ca(OH)2 solution, 1 week; group 5--3% NaOCl, 2 h and then saturated
      Ca(OH)2 solution 1 week; group 6--5% NaOCl, 2 h and then saturated Ca(OH)2
      solution 1 week. The dentine bars were then loaded to failure in a three-point
      bend test. RESULTS: The data revealed a significant (P < 0.001) decrease in the
      modulus of elasticity and flexural strength of the dentine bars treated with 3%
      and 5% NaOCl. There was no significant difference in the flexural strength and
      the modulus of elasticity between the 3% and 5% NaOCl groups. Exposure to Ca(OH)2
      significantly (P < 0.001) reduced the flexural strength but had no significant
      effect on the modulus of elasticity. The groups treated with sodium hypochlorite
      followed by calcium hydroxide did not have moduli of elasticity and flexural
      strengths that were significantly different from those treated only with sodium
      hypochlorite. CONCLUSIONS: NaOCl (3 & 5%) reduced the modulus of elasticity and
      flexural strength of dentine. Saturated Ca(OH)2 reduced the flexural strength of
      dentine but not the modulus of elasticity. Sequential use of NaOCl and Ca(OH)2
      has no additional weakening effect.

PMID- 11307260
TI  - Effect of sodium hypochlorite on mechanical properties of dentine and tooth
      surface strain.
AB  - AIM: The aim of this study was to test the null hypothesis that sodium
      hypochlorite irrigation of root canals does not alter the properties of dentine
      and contribute to the weakening of root-treated teeth. METHODOLOGY: The effect of
      two concentrations (0.5%, 5.25%) of sodium hypochlorite (NaOCl) and saline on (i)
      the elastic modulus and flexural strength of machined dentine bars, and (ii)
      changes in strain of 'whole' extracted human teeth were evaluated. One hundred
      standardized plano-parallel dentine bars (> 11.7 x 0.8 x 0.8 mm) were randomly
      divided into the three groups, immersed for 2 h in the respective solutions and
      then subjected to a three-point bend test. Changes in strain of each of 10 teeth
      on cyclical nondestructive occlusal loading were measured using electrical
      resistance strain gauges bonded to the cervical aspects. Each tooth had its crown
      and enamel reduced and root canal prepared. These were irrigated sequentially in
      a series of four separate, 30-minute regimes; initial-saline, 0.5% NaOCl, 5.25%
      NaOCl and final-saline. The changes in strains after each irrigation regime were
      compared. RESULTS: There was a significant decrease in elastic modulus of the
      dentine bars immersed in 5.25% NaOCl compared with the saline group (P < 0.01).
      There was also a significant decrease in flexural strength of the dentine bars in
      the 5.25% NaOCl group compared to both the saline and 0.5% NaOCl groups (P <
      0.01). The strain data from the nondestructive tooth loading tests revealed
      significant increases in tensile strain between the initial-saline and the final
      saline stages (P < 0.01). Significant increases in compressive strains were also
      found between initial-saline and 5.25% NaOCl; and between 0.5% NaOCl and 5.25%
      NaOCl stages (P < 0.01). CONCLUSIONS: The null hypothesis was rejected, 5.25%
      NaOCl reduced the elastic modulus and flexural strength of dentine. Irrigation of
      root canals of single, mature rooted premolars with 5.25% NaOCl affected their
      properties sufficiently to alter their strain characteristics when no enamel was
      present.

PMID- 11307261
TI  - Dye penetration in dry and water-filled gaps along root fillings.
AB  - AIM: The aim of this study was to investigate the influence of hydration in voids
      along root fillings on methylene blue penetration. METHODOLOGY: A total of 80
      human root canals were prepared using a step-back technique and filled with a
      zinc oxide based sealer and gutta-percha. Leakage along the fillings was measured
      by a transport fluid model and classified into three categories: gross leakage
      (GL), slight leakage (SL) and no leakage (NL). Specimens with NL and SL were
      immersed into methylene blue (MB) 2% for 24 h (group I). Specimens with GL which
      had wide gaps filled with water were randomly divided into two groups (II, III).
      Transport air was applied to remove water from gaps only in specimens of group
      III. All tested specimens from groups II and III were also immersed into MB 2%
      for 24 h. Each specimen was then split longitudinally and linear measurements of
      dye penetration were recorded. RESULTS: Group III (with dry gaps) showed
      significantly more dye penetration than group II. No significant difference was
      found between group I and group II. CONCLUSIONS: Methylene blue penetrates along
      root fillings more easily in dry gaps than in water-filled gaps.

PMID- 11307262
TI  - A primary observation on the preparation and obturation of oval canals.
AB  - AIM: The aim of this study was to observe the existence and assess the quality of
      obturation of uninstrumented recesses in oval canals. METHODOLOGY: The balanced
      force technique was used in two groups of oval canals in human mandibular
      incisors. The canals in group 1 were enlarged to conventional sizes, whereas
      canals in group 2 were enlarged more widely. All canals were obturated with cold
      laterally condensed gutta-percha. Two horizontal sections were cut in the apical
      portion of each filled root. Images of the cross-sections were scanned and
      analysed using the KS100 Imaging system. RESULTS: Uninstrumented recesses
      appeared in 13 (65%) oval canals. The recesses in five of these 13 canals were
      obturated without visible voids. The recesses in the other eight canals were
      either obturated with visible voids or completely unfilled. The percentage of
      filled area was significantly higher in group 1 than in group 2 (P < 0.05).
      CONCLUSIONS: Uninstrumented recesses may be left in many oval canals after
      preparation using the balanced force technique and these recesses may often not
      be completely obturated with cold laterally condensed gutta-percha.

PMID- 11307263
TI  - An in vitro study comparing root-end cavities prepared by diamond-coated and
      stainless steel ultrasonic retrotips.
AB  - AIM: This study compared the appearance of root-end cavity preparations and the
      time required to prepare them using prototype ultrasonic diamond-coated (DC) and
      stainless-steel (SS) retrotips. METHODOLOGY: In 12 maxillary and 12 mandibular
      molar teeth 48 root-end cavities were prepared ultrasonically in the palatal,
      mesio-buccal, distal and mesial root-ends using DC and SS retrotips, alternately.
      Replicas of the resected root tips and the root-end cavities were examined under
      a scanning electron microscope (SEM), recording (i) incidence and extent of
      dentine cracks (ii) minimum remaining thickness of the dentine walls and (iii)
      surface quality of the resected root-ends. The time taken to complete the
      preparation was also recorded. Means of these parameters were compared for both
      types of retrotips using nonparametric tests. RESULTS: No resected root-ends had
      cracks before preparation. However, after preparation one root-end cavity shaped
      by an SS retrotip had a microcrack visible at 23x magnification. Four and seven
      other root-ends had crazed surfaces in the DC and SS groups, respectively (P >
      0.05). Remaining minimum dentine thickness was 0.56 +/- 0.28 mm and 0.71 +/- 0.24
      for the DC and SS groups, respectively, and this difference was significant (P <
      0.05). A root-end cavity in one specimen in the DC group was perforated.
      Preparation times ranged from 25 s to 361 s and were significantly lower for DC
      tips (P < 0.01) than the SS tips. The time required to prepare root-end cavities
      also differed between roots; root-end preparation in mandibular molars was more
      time consuming. CONCLUSIONS: A better quality surface was produced by the
      prototype diamond-coated retrotips, in less time than the SS retrotips, which in
      turn caused fewer cracks than previously reported. DC retrotips removed more
      dentine than SS retrotips and should therefore be used with care to avoid
      overpreparation or perforation.

PMID- 11307264
TI  - The standardized-taper root canal preparation--Part 3. GT file technique in large
      root canals with small apical diameters.
AB  - AIM: To describe the preparation of Large Root canals with small apical diameters
      by the GT file technique. SUMMARY: Large Root canals with small apical diameters
      can usually be prepared with one to three GT files; one to nine clinical steps,
      and one to five minutes of clinical time. Following proper access, pulp tissue
      should be removed, and lubricant applied to prevent pulp compaction and blockage.
      Initial crown-down enlargement is accomplished with up to three standard GT
      rotary files 0.10, 0.08 and 0.06 taper, running at 300 r.p.m., and with light
      touch. Care should be taken not to overload instruments, and they should be
      withdrawn, cleaned and inspected whenever they bind. Sometimes, the shaping
      objective is achieved with a single instrument; often waves of instrumentation
      are required before the shaping objective file cuts to length. Prior to cone-fit,
      the apical resistance form is confirmed with conventional files, employed as
      feeler gauges of the tapering form created at the canal terminus. Regardless of
      the shaping time, canals should be soaked with sodium hypochlorite solution for
      at least 30 min for effective cleaning. KEY LEARNING POINTS: Large Root canals
      with small apical diameters should be prepared to shaping objectives 0.08 or 0.10
      taper. Compacted pulp tissue causes many canal blockages. It should be removed
      early, and canals should be well lubricated. Large Root canals with small apical
      diameters should be prepared in crown-down sequence, with recapitulation of steps
      until the shaping objective is achieved. Apical resistance form should always be
      confirmed before cone-fit. Canals should be exposed to sodium hypochlorite for at
      least 30 min for effective cleaning.

PMID- 11307265
TI  - The standardized-taper root canal preparation--Part 4. GT file technique in large
      root canals with large apical diameters.
AB  - AIM: To describe the GT file shaping steps required to create apical resistance
      in the presence of a wide root apex. SUMMARY: Canals are occasionally encountered
      with apices wider than 0.25 mm. These can be some of the most difficult to manage
      with conventional instruments, and overfills are common. Shaping such canals with
      GT files requires a paradigm shift of thinking, extending tapered files through
      the apex to create linear resistance in the apical few mm of the canal. GT
      standard and accessory files allow canals with apices up to around 0.7 mm to be
      prepared for tapered gutta percha cone-fit. Apices larger than this should be
      considered too large for further shaping, and repaired with MTA before filling.
      KEY LEARNING POINTS: Tapered apical preparations offer optimal resistance form
      for obturation. Tapered apical preparations can be prepared in most roots with
      wide apices by extending GT files and GT accessory files to or through the apex.
      Apices wider than 0.7 mm should be repaired with MTA prior to filling.

PMID- 11307266
TI  - The influence of ultrasound on the retention of cast posts cemented with
      different agents.
AB  - AIM: The aim of this study was to evaluate the influence of ultrasound during the
      removal of posts cemented with either zinc phosphate cement, glass ionomer cement
      or resin cement. METHODOLOGY: Eighty-four single-rooted teeth were prepared and
      after cementation of cast posts, they were randomly divided into six groups of
      14. Group 1, 2 and 3 did not receive ultrasonic vibration, whilst groups 4, 5 and
      6 received ultrasonic vibration for 10 min. The force necessary for post removal
      was determined using a universal testing machine. Results were statistically
      analysed using ANOVA and Tukey tests (5%). RESULTS: The application of ultrasonic
      vibration reduced the retention provided by zinc phosphate and glass ionomer
      cements by 39% and 33%, respectively. CONCLUSIONS: A statistically significant
      reduction in the force necessary to remove posts cemented with zinc phosphate and
      glass ionomer cements occurred following application of ultrasound. The
      application of ultrasonic vibration did not influence the retention of cast posts
      cemented with resin cement.

PMID- 11307267
TI  - The orthodontic shift towards functional jaw orthopedics.
AB  - FJO treatment is exceptionally unique and differs dramatically from traditional
      orthodontics. Parents are demanding earlier treatment, less bicuspid extractions,
      and broader smiles. A national trend towards FJO treatment methods will continue
      because FJO treatment has been shown to be medically effective for a number of
      common human disorders. Progressive dentists who provide cutting edge FJO therapy
      are uniquely positioned to impact human development and general health starting
      at birth, in ways yet to be charted. Early FJO treatment fulfills the ADA Code of
      Ethics which "calls upon dentists to follow high ethical standards which have the
      benefit of the patient as their primary goal: Do No Harm and Do Good."

PMID- 11307268
TI  - Some thoughts about orthodontics and TMJ troubles.

PMID- 11307269
TI  - Ankyloglossia and its influence on maxillary and mandibular development. (A seven
      year follow-up case report).
AB  - The consequences of not treating improper tongue function may be very important
      as this organ can influence face development and dental therapy. The role of the
      tongue in the development of the skeletal structures of the face has been
      considered in different perspectives over the years. For some, the tongue adapts
      to the "tongue box," for others the "tongue box" has been created and stabilized
      by the morphogenetic action of the tongue during development and growth. A case
      of ankyloglossia treated with lingual frenectomy and followed clinically and
      radiologically for seven years is reported. Spontaneous upper arch expansion
      occurred and therefore orthodontic treatment following surgical intervention was
      unnecessary.

PMID- 11307270
TI  - Chewing and occlusal function.
AB  - Full diagnostic records are a medical-legal necessity to diagnose, treatment
      plan, monitor clinical progress, and evaluate outcome. "We (orthodontists) have
      been concerned with the anatomical relations of the teeth, the relation of the
      mandible to the maxilla, the relation of the teeth in the entire facial
      component, but this is not enough. We must enlarge our scope of knowledge and
      responsibilities to be equally concerned and competent as physiological
      orthodontists." (Thompson) Treatment outcome distinction is made between static
      evaluation of records and "plaster models on the table", and functional
      evaluation of the finished case. Most occlusal "chewing" function occurs with the
      first molar and premolar teeth. It is reported that 90% of chewing function is
      first molar and bicuspid region. Physiologically oriented orthodontists must
      consider: soft tissue profile and facial esthetics, incisal misguidance
      (interference), narrow or constricted maxilla, underdeveloped or retruded
      maxilla, overdeveloped or prognathic mandible (Class III actual of effective
      condition relative to maxilla), crowding or displacement of teeth, and (TMJ)
      temporomandibular joints must be considered. Second molars are the common cause
      of working balancing, and protrusive occlusal disturbances. The mesial distal
      width of second molar teeth and premolar teeth is not significantly different.
      Second molar replacement is a viable option for many patients (not all)
      undergoing orthopedic and orthodontic treatment who require removal of teeth for
      treatment purposes. The most important teeth for chewing are first molar to first
      molar teeth.

PMID- 11307271
TI  - Class I, pseudo-Class I, super Class I: which is it and why is it important?

PMID- 11307272
TI  - Surgeon general's report a call to action on oral health. HSDM programs
      addressing disparity on access to care.

PMID- 11307273
TI  - Dental training applied to the arts.

PMID- 11307274
TI  - [Acute pulmonary artery thromboembolism].

PMID- 11307275
TI  - [Epidemiology of acute pulmonary thromboembolism].

PMID- 11307276
TI  - [Etiological factors and symptoms of acute pulmonary thromboembolism].

PMID- 11307277
TI  - [Pathology of acute pulmonary thromboembolism].

PMID- 11307279
TI  - [Hemodynamics in acute pulmonary thromboembolism].

PMID- 11307278
TI  - [Thrombotic diathesis and acute pulmonary thromboembolism].

PMID- 11307280
TI  - [Diagnosis of acute pulmonary thromboembolism: electrocardiography,
      echocardiography, and thoracic radiography].

PMID- 11307281
TI  - [Diagnosis of acute pulmonary thromboembolism: blood gas analysis].

PMID- 11307282
TI  - [Diagnosis of acute pulmonary thromboembolism: application of techniques of
      nuclear medicine].

PMID- 11307283
TI  - [Diagnosis of acute pulmonary thromboembolism: CT].

PMID- 11307284
TI  - [Diagnosis of acute pulmonary thromboembolism: angiography of the pulmonary
      artery].

PMID- 11307285
TI  - [Therapeutic approach in acute pulmonary thromboembolism: thrombolytic therapy].

PMID- 11307286
TI  - [Therapeutic approach in acute thromboembolism: An inferior vena cava filter].

PMID- 11307287
TI  - [Therapeutic approach in acute pulmonary thromboembolism: surgical therapy].

PMID- 11307288
TI  - [Treatment of deep venous thrombosis].

PMID- 11307289
TI  - [Prevention of acute pulmonary thromboembolism].

PMID- 11307290
TI  - [Intravascular ultrasonography and angioscopic examination of pulmonary
      thromboembolism].

PMID- 11307291
TI  - [Diagnosis and treatment of acute pulmonary thromboembolism: discussion].

PMID- 11307292
TI  - [Idiopathic hypoparathyroidism with neurological manifestations: successful
      treatment with vitamin D3].

PMID- 11307293
TI  - [Pure red cell aplasia due to persistent human parvovirus B19 infection in
      healthy adult].

PMID- 11307294
TI  - [Sarcoidosis with diabetes insipidus and pituitary tumor].

PMID- 11307295
TI  - [A case of Sjogren syndrome associated with bronchiolitis obliterans organizing
      pneumonia].

PMID- 11307296
TI  - [Propylthiouracil induced ANCA-associated nephritis occurred in the course of
      membranous nephropathy].

PMID- 11307297
TI  - [Response to respiratory tract infections of the aged].

PMID- 11307298
TI  - [Current status of kidney transplantation].

PMID- 11307299
TI  - [Diagnosis and treatment of diabetic nephropathy].

PMID- 11307300
TI  - [The history of Helicobacter pylori].
AB  - Histological and ultrastructural studies of gastric mucosa with spiral bacteria
      had been published at the Royal Perth Hospital of Western Australia in 1979. The
      pathologist Warren correlated them with inflammation. In 1981, Marshall was
      training in internal medicine. Warren, Marshall and Goodwin started culture of
      bacteria, but spiral bacteria were not cultured. The 35th culture was left during
      the Easter holiday, and after 5 days 1-mm transparent colonies were seen on the
      plate. Since discovery Helicobacter pylori(H. pylori) have continued to fascinate
      and challenge doctors and scientists for 18 years to come. In 2000, triple
      therapy with PPI, Amoxicillin and clarithromycin was approved for treatment of
      peptic ulcer disease in Japan.

PMID- 11307301
TI  - [Analysis of virulence factors of Helicobacter pylori].
AB  - Many virulence factors of Helicobacter pylori have been reported. Analysis of
      such virulence factors in relation to the occurrence of gastroduodenal diseases
      is discussed. Several adhesins of H. pylori are involved in its adhesion to
      gastric epithelial cells, and urease activity is necessary for its colonization
      in acidic gastric mucosa. Vacuolation cytotoxin(VacA)-positive Type I strains are
      frequently isolated from the patients with peptic ulcer diseases in western
      countries, but not in east Asia. CagA has been reported to be transported into
      epithelial cells through type IV secretion machinery coded by genes in cag
      pathogenicity island(PAI) and phosphorylated by cellular tyrosine kinase. Heat
      shock protein is also considered to be a virulence factor to play a role of
      triggering autoimmune response, stimulating its adhesion and inducing several
      cytokines.

PMID- 11307302
TI  - [Helicobacter pylori & gastric disease].
AB  - Since the discovery of Helicobacter pylori(H. pylori), causal linkage between H.
      pylori infection and some of gastric disease has been generally accepted from the
      results of many studies. Indeed the usefulness of H. pylori eradication therapy
      for acute gastritis, peptic ulcer, gastric polyp and MALT lymphoma etc. has been
      reported. In the low grade MALT lymphoma, the regression rate by this therapy is
      about 70%. On the other hand, we should pay the caution to several adverse
      effects, such as drug resistance and GERD, of H. pylori eradication therapy.
      However, based on the several results of comparative studies between antibiotic
      therapy and the other one, the antibiotic therapy for peptic ulcer is only
      covered by national health insurance at present. The reversibility of gastric
      precancerous conditions such as mucosal atrophy, intestinal metaplasia and
      dysplasia by antibiotic therapy has been studied, but its significance is not
      clear yet. In animal experiment, H. pylori infection induced gastric
      adenocarcinoma in Mongolian Gerbils. However, this phenomenon is limited to this
      kind of animal only. To proof the causal link between H. pylori infection and
      genesis of gastric cancer in human being, clinical intervention trials are
      ongoing in the world. If these trials can clarify it, the H. pylori eradication
      therapy will be established as preventive measure for gastric carcinogenesis.

PMID- 11307303
TI  - [New evidence for detecting Helicobacter pylori in clinics].
AB  - A part of diagnostic tests for Helicobacter pylori was approved as National
      Health Insurance system in Ministry of Health and Welfare Japan on last November
      2000. The gold standard for the presence of most infectious diseases is
      successful culture of the organism. H. pylori is fastidious and time consuming
      for growth in media. Instead of bacterial culture of H. pylori from biopsy
      sample, we need to effort to develop rapid methods to identify gene segment of H.
      pylori and its antibiotic resistance. Even the genetic methods would be
      developed, circular antigen product of H. pylori must be important for diagnosis
      of its clinical pathology. Here we listed the available diagnostic tests for
      histology, bacterial culture, rapid urease test, urea breath testing, and
      serological testing for H. pylori in Japan.

PMID- 11307304
TI  - [Eradication therapy of Helicobacter pylori infection].
AB  - Helicobacter pylori(H. pylori) infection is recognized to be a pathogen of
      various gastro-duodenal diseases. Eradication therapy of H. pylori reduces the
      recurrence of gastro-duodenal ulcer, and improves gastritis histologically.
      Recently, proton pump inhibitor(PPI) based triple therapy, that combining PPI,
      clarithromycin, amoxicillin is widely accepted throughout the world, and shows
      high eradication rate which ranged about 80-90%. In Japan, one week triple
      therapy is recommended for the treatment of gastro-duodenal ulcer, though it is
      expected the improvement of recurrent peptic ulcer. In the present studies, the
      rate of clarithromycin resistant strains has been increased gradually, and this
      fact may lead to the development of failure of PPI based triple therapy. Another
      problem is suggested by several studies that gastro-esophageal reflux
      disease(GERD) may increase after successful eradication of H. pylori. Reflux
      esophagitis and Barrett's esophagus are recognized as precancerous lesion of
      esophageal adenocarcinoma, but the association of newly occurrence of GERD after
      H. pylori eradication and increase of esophageal adenocarcinoma is not clear.
      Merits and demerits of H. pylori eradication need to be observed carefully over a
      long term.

PMID- 11307305
TI  - [Helicobacter pylori test and medical reimbursement].
AB  - There are an estimated 60 million people with Helicobacter pylori(H. pylori)
      infection who occupied 50% of the population of Japan. In Japanese medical
      reimbursement H. pylori tests were introduced on November 1, 2000 and they are
      able to use only to patients with gastric and duodenal ulcer. H. pylori tests
      were composed of rapid urease test, urea breath test, antibody test, bacterial
      culture and pathologic test. Payment of each test is 700 Yen. Classification and
      cost of H. pylori tests are shown. Usage of laboratory tests for H. pylori
      infection is mentioned. Those particular tests are useful to decrease the number
      of gastric and duodenal ulcer in Japan.

PMID- 11307306
TI  - [The present status and future prospect of the molecular diagnostic tests].
AB  - Assays for DNA or RNA sequences to diagnose infectious, neoplastic and genetic
      diseases have been widely used through recent progress in the molecular biology
      and biotechnology, and are now essential in care of patients under the advanced
      medicine through earlier and more accurate diagnosis. Automated systems have been
      developed for amplification and detection of nucleic acid sequence for infectious
      agents, using various nucleic acid amplification technology such as PCR. A fully
      automated PCR system and automated extraction of specific sequence for infectious
      agents such as hepatitis C virus RNA has been developed. These automated systems
      have provided improvement of not only assay efficiency but also quality control
      of the tests and have contributed to the standardization of them. Importance of
      development of systems for quality assessment and laboratory accreditation has
      been emphasized, particularly in those that still have been performed with manual
      methods. Based on the information on the genome sequence as the outcome of the
      human genome project, functions of genes and proteins have been studied by post
      genomics such as expression profiling using DNA microarray, proteomics, single
      nucleotide polymorphisms analysis, coupled with bioinformatics. Along with
      advances in pharmacogenomics, these studies have raised the prospect of the
      development of tests for individualized medicine based on genetic information
      such as those predicting individual susceptibility to diseases for prevention and
      responsiveness to drugs for choice of treatment. For practice of such medicine,
      each genetic information and tests for it must be carefully evaluated and
      determined whether it is appropriate for cost-effective medicine through
      contributions to efficient process of decision-makings on patient care for
      prevention or avoidance of diseases and thus to cost savings.

PMID- 11307307
TI  - [Clinical significance and strategies to analyze genetic polymorphisms].
AB  - A DNA polymorphism can be defined as a difference in the primary sequence of DNA,
      and the frequency of the rarer allele among the general population exceeds 1%.
      Several types of polymorphisms, including minisatellite and microsatellite
      markers, deletion or insertion of short nucleotide sequences, and single
      nucleotide polymorphisms(SNPs), are present in human genome, with different
      frequencies and different distribution patterns. SNPs are very common and
      clinically important, because they often appear within genes, particularly within
      coding sequences. The biological significance of a polymorphism differs
      significantly depending upon its location within the genome. For example,
      polymorphisms located outside genes usually do not have biological consequences,
      and will be used merely as markers for genetic linkage. On the other hand, those
      located within a gene may cause subtle changes in transcription, mRNA stability,
      or protein conformation if amino acid substitution occurs. These subtle changes
      in biologically important factors then alter susceptibility to certain disorders.
      Environmental factors often interact with genes. Relationships between genetic
      polymorphisms and disease susceptibility have been reported on many kinds of
      human diseases, including neurological and psychiatric disorders, infectious
      diseases, endocrine and metabolic disorders, malignancy, as well as
      cardiovascular diseases. Recent years have seen the progress in novel strategies
      for rapid genotyping of a large numbers of polymorphisms, and also, for searching
      unknown SNPs.

PMID- 11307308
TI  - [Hypertension and gene polymorphisms].
AB  - For our understanding of the genetic factors of human essential hypertension,
      gene polymorphisms have played a significant role as DNA markers in association
      and linkage studies. We found positive linkages between hypertension and 4 gene
      polymorphisms including angiotensinogen Met235Thr, angiotensin converting enzyme
      I/D, aldosterone synthase CYP11B2 T-344C, and endothelial nitric oxide synthase
      Glu298Asp in the Aomori population. These results suggest that the 4 gene
      polymorphisms might be genetic risk factors for hypertension in this district.
      However, there has been a frustration with the inconsistencies of accumulated
      evidence. Because, the genetic associations tend to vary across race, ethnicity,
      and ecological states. Thus, the rates of racial inter-mixture can explain
      regional differences in disease susceptibility. We emphasize that human lineage
      based analysis across populations may lead to the better understanding of the
      variability.

PMID- 11307309
TI  - [Diabetes mellitus].
AB  - Diabetes mellitus is a group of metabolic disorders characterized by
      hyperglycemia resulting from defects in insulin secretion, insulin action or
      both. Genetic factors contribute to the development of diabetes. Some forms such
      as the condition called maturity-onset diabetes of the young(MODY) result from
      mutations in a single gene. Other forms such as type 1 or type 2 diabetes are
      multifactorial in origin with different combinations of genes together with non
      genetic factors contributing to the development of hyperglycemia. MODY has been a
      good model for studying the genetics and pathophysiology of diabetes. This form
      of diabetes can result from mutations in at least seven different genes:
      hepatocyte nuclear factor(HNF)-4 alpha/MODY1, glucokinase/MODY2, HNF-1
      alpha/MODY3, insulin promoter factor(IPF-1)/MODY4, HNF-1 beta/MODY5,
      NeuroD1/MODY6 and Islet(Isl)-1/MODY7. Mutations in HNF-1 alpha/MODY3 are the most
      common cause of MODY in Japanese identified to date accounting for about 15% of
      cases of MODY. Mutations in the HNF-4 alpha/MODY1, glucokinase/MODY2, HNF-1
      beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they
      are rare causes of MODY. Clinical studies indicate that patients with MODY are
      generally not obese and that all forms of MODY are characterized by pancreatic
      beta-cell dysfunction. Patients who have mutations in the HNF-1 beta/MODY5 gene
      have non-diabetic kidney dysfunction including renal cysts. Female carriers may
      also exhibit abnormalities in the upper vagina and uterus. Genetic approach for
      type 2 diabetes had done by using non-parameteric linkage analysis such as
      sibpair analysis which worked well and NIDDM1 and NIDDM2 have been identified to
      date. The responsible gene for NIDDM1 was recently identified to be Calpain 10,
      and SNP43 in this gene could explain all of the evidence for linkage in Mexican
      American type 2 diabetes.

PMID- 11307310
TI  - [Genetic polymorphism and risk of thromboses].
AB  - We have attempted to establish a systematic pathogenetic analysis of
      thrombophilia by including assays of antithrombin III(AT III), protein C(PC),
      protein S(PS), fibrinogen, plasminogen and heparin cofactor II by both functional
      and immunological methods as well as detecting lupus anticoagulants. Such a
      comprehensive scheme was instrumental in systematically identifying and
      confirming the pathogenesis of 164 cases which otherwise would have escaped
      detection since 1994 in our laboratory (Kyushu University Hospital). The analysis
      was conducted on 485 consecutive patients with venous thrombosis, arterial
      thrombosis and disorders in which small vessel thrombosis were implicated.
      Hundred and sixty four patients, (40% of the examined patients), were found to
      have low activities of PS, PC, ATIII etc. Among them, seventy five patients(46%)
      had low PS activity, and twenty nine(18%) had low PC activity. Genetic analyses
      performed on specimens with low PS/PC activities resulted in the confirmation of
      24 genetic abnormalities. Such genetic abnormalities, however, does not solely
      lead to the pathogenesis of thromboses. We have found that some genetic
      polymorphisms, such as PS Tokushima, factor XII 46C allele, were also additional
      risk factors for thromboses.

PMID- 11307311
TI  - [Genetic polymorphism and cancer].
AB  - The clinical pathological significance of genetic polymorphism in cancer is
      reviewed from the following standpoint. 1) Genetic diagnosis of cancer,
      especially for loss of heterozygosity 2) Interference with laboratory data: For
      example, the polymorphisms in secretor and Lewis genes make effect on the serum
      levels of CA19-9. 3) Cancer susceptibility: Molecular epidemiological studies
      revealed some genetic polymorphisms were related with cancer susceptibility and
      were useful for biomarkers of cancer risk. 4) Drug sensitivity: The differences
      in drug toxicity are sometimes attributed to genetic variability in some enzymes
      responsible for drug metabolism. When the polymorphisms related with drug
      degradation were examined, the exact drug would have been selected for each
      individual. Genetic polymorphisms are strongly related with clinical practice of
      cancer. After the information about genetic polymorphisms is accumulated, tailor
      made medicine(therapy/prevention/diagnosis) will be applicable to medical care of
      individuals.

PMID- 11307312
TI  - [Recent progress in laboratory standardization and clinical chemistry].

PMID- 11307313
TI  - [Establishment of a reference interval for highly sensitive CRP by exclusion of
      individuals with abnormal values in related laboratory tests].
AB  - In November, 1999, U.S. Food and Drug Administration approved a highly sensitive
      CRP(hs-CRP) assay that could assist medical doctors to predict the risk of
      cardiovascular accidents. Many doctors are now interested in the assay and trying
      to elucidate the relationship between serum CRP levels and cardiovascular
      diseases. In the past, it was difficult to establish a valid reference interval
      of serum CRP because of the poor analytical sensitivity and difficulty in
      sampling reference individuals. We have established a reference interval of serum
      CRP for the hs-CRP assay(Dade Behring). The study population consisted of 7,224
      individuals(21-81 years old) who received a regular medical check-up. Potentially
      abnormal samples were excluded, depending on the results of other laboratory
      tests related to serum CRP variation. The upper limit of the reference interval
      was 0.15 mg/dl. The serum CRP was higher in smokers than in non-smokers,
      especially in men.

PMID- 11307314
TI  - [Efficacy of radiofrequency catheter ablation in a patient with sinus node
      reentrant tachycardia].
AB  - We performed electrophysiological study and catheter ablation on a 62-year-old
      patient with supraventricular tachycardia(SVT). This SVT was reproducibly
      initiated and terminated by atrial stimulation during the electrophysiological
      testing. The P-wave morphology and atrial activation sequence of intracardiac
      electrograms were identical to those in normal sinus rhythm. SVT was terminated
      with carotid sinus massage that increased vagal tone, and for this reason, the
      reentry circuit of SVT could be localized in sinus node. On the basis of these
      findings, the SVT was diagnosed as sinus node re-entrant tachycardia and was
      successfully eliminated by radiofrequency catheter ablation. Radiofrequency
      catheter ablation would be effective in patients with sinus node reentrant
      tachycardia refractory to anti-arrhythmic drugs. It should, however, be performed
      with careful consideration to the influence of the sinus node.

PMID- 11307315
TI  - [A case of Miller-Dieker syndrome associated with satellite on chromosome 17p].
AB  - In this report, we describe a one-year-old girl of the Miller-Dieker
      syndrome(MDS) with lissencephaly, seizures, microcephaly and mental disorders.
      Cytogenetic studies of this patient confirmed the presence of a 46,XX, 17ps+
      chromosome karyotype, but it could not find the microdeletion of 17p13.3.
      Fluorescence in situ hybridization(FISH) studies confirmed a terminal deletion in
      the patient using the LIS1 gene probe which mapped to 17p13.3. Further it was
      also found the satellite on 17p13(17ps) in the patient who was rare associated
      with MDS. These findings suggest that FISH analysis may be useful method to
      detect microdeletion of LIS1 gene as 17-specific probe in the investigation of
      MDS patients.

PMID- 11307316
TI  - [Molecular diagnostic tests in hematologic diseases].
AB  - Molecular diagnostic tests are widely performed in managing hematologic
      malignancies such as leukemia and lymphoma. In this article, we review the
      present application and problems of the tests. Karyotyping is performed at
      diagnosis of all kinds of hematologic malignancies. This method needs dividing
      cells as samples and skilled experts. Fluorescence in situ hybridization(FISH)
      analysis using cells in interphase is performed, for example, to monitor the
      effect of interferon on chronic myelogenous leukemia patients. The weak point of
      this method is that approximately 2% of false-positive cells are inevitable.
      Southern blot method is used for clonal analysis in some disease, for example,
      adult T-cell leukemia/lymphoma. Polymerase chain reaction(PCR) method using
      genomic DNA is performed for limited types of diseases such as lymphoma with bcl
      2/IgH fusion gene. Reverse transcription(RT)-PCR method can detect fusion gene
      transcripts with high sensitivity. This method is useful for detecting minimal
      residual diseases after chemotherapy or bone marrow transplantation. To perform
      quantitative analysis, real-time PCR or competitive PCR must be done. In the near
      future, new technology such as gene expression profiling analysis using DNA
      microarrays or spectral karyotyping(SKY) method will be used in clinical
      practice.

PMID- 11307317
TI  - [Analyses of preanalytical issues on samplings and samples].
AB  - To obtain "exact" laboratory data which show or reflect the pathophysiological
      conditions of patients, preanalytical, analytical and postanalytical processes
      should be checked. However, it is difficult to know the preanalytical situation
      or out of laboratories. We realize preanalytical issue is one of the weak points
      in current laboratory medicine. I reported the results of analyses on the issues
      concerning abnormal laboratory data produced by inadequate handling of samples
      and sample collection. Five issues are described as follows: 1) The effect of
      detergents on fecal occult blood test. Immunological methods were affected
      markedly to moderately by various sanitizers and detergents tested. In collecting
      feces for immunological fecal occult blood test, contact of feces with toilet
      flush water dissolving sanitizers should be inhibited. 2) Blood storage and
      potassium(K) release. Causes of slight elevation of K in serum are sometimes
      unknown. Addition of injection drugs in vitro showed that various drugs induced K
      release from erythrocytes. Cold storage of blood is well-known to bring elevation
      of K level, however, the detailed mechanism is still unknown. We developed a
      simple method to measure K flux activity of erythrocytes and the decreased
      activity was shown in patients with chronic renal insufficiency and the aged as
      well as the aged erythrocytes. 3) Thawed serum and concentration difference.
      Frozen serum samples were thawed without mixing and various layers contained
      different concentrations in 60 items tested. Comparing the concentration before
      freezing, the upper layer contained 1/2 and the bottom 2 times more. T3 and FT4
      showed exceptionally smaller difference, significance of which is unknown. 4) Two
      syringe method in blood collection. Blood samples drawn in the first half and the
      latter half were comparatively measured for APTT, PT and TT. Blood amount of 1 ml
      or more showed no differences. TT showed elevation in the first half in 0.5 ml
      sample. The effects of local treatment by warming, tapping and congestion were
      examined. In some cases, tissue factor level elevated by such physical
      pretreatment. However, in usual blood collection in human, two syringe method is
      not necessarily employed. 5) Heat-inactivation and cold storage of serum.
      Preheating sera at 56 degrees C for 30 min reduced markedly the levels of ALT,
      ALP, CK, ChE, ATIII and alpha 2-PI. In seroimmunology, some complement components
      are markedly affected and rheumatoid factor of IgM classes was also affected. In
      about a half of HCV-Ab positive sera, CH50 levels were decreased by the cold
      storage(cold activation). We reported previously the non-participation of C1q in
      this phenomenon. In such sera, temperature management is important. Scientific
      data on the storage and collection of samples should be informed not only to
      laboratory staffs but to nurses and doctors in order to provide "exact" data.

PMID- 11307318
TI  - [Advances in immunoserology tests in clinical medicine: autoantibodies, immune
      complexes and DNA analysis].
AB  - I reviewed first the history of detection for autoantibodies and the methods to
      detect the circulating immune complexes. Then I presented several unusual tests
      for detecting autoantibodies which I had experienced. They are agglutination
      tests in agarose gel using the particulate antigens of human tissues or lipid
      antigens and the mixed agglutination test using the cultured cells. The
      characteristics of rheumatoid factor(RF) were analyzed by the following methods:
      1) solid-phase radioimmunoassay for IgG-RF using the formalinized sheep RBC, 2)
      mixed agglutination test for IgG-RF on the slide glass smeared with the
      sensitized sheep RBC, 3) hemolysis in agarose gel for competitive reaction of RF
      with complement to the IgG hemolysin and 4) ELISA for detecting the complement
      fixation of the monoclonal IgM-RF. The IgG-Fc and C3b receptors on the tissue
      sections of the mammalian aorta were detected by an adhesion of the IgG
      sensitized or C3b-bound RBC. DNA-analysis studies using the molecular biology
      techniques which were done in the Department of Internal Medicine II, Fukushima
      Medical University were presented. 1) Nucleic acid sequences of the cloned DNA
      polypeptide fragments in the serum of patients with systemic lupus erythematosus.
      2) SSCP analysis for clonality of Vb repertoires in T cell receptors in the
      patients with rheumatoid arthritis, primary biliary cirrhosis or CREST syndrome.
      3) Detection of mRNA of TNFa and Fas ligand in the mononuclear cells(FICL-PCR) in
      the synovial fluids of RA patients.

PMID- 11307319
TI  - [Regulatory factors for changing laboratory data before and after dialysis
      therapy].
AB  - The proper assessment of laboratory data in dialysis patients is important to
      maintain the effectiveness of therapy. The factors for regulating laboratory data
      in dialysis patients are as follows: 1. abnormal data associated with renal
      dysfunction(uremic state). 2. changes in laboratory data related to dialysis
      therapy. 3. changes in data related to biocompability for dialysis. 4. changes in
      data related to movement of fluid between different compartments. 5. changes in
      data related to different methods of therapy. The goal of this discussion is to
      describe the general principles for the assessment of laboratory data in dialysis
      patients, to offer a good therapy and to provide the best outcome in order to
      improve the ADL and QOL in the patients.

PMID- 11307320
TI  - [Disorders of potassium metabolism in hemodialysis patients].
AB  - The fecal K concentration and the K-flux activity of erythrocytes were examined
      to investigate the role of extrarenal K excretion and K transport in peripheral
      tissue cells in hemodialysis patients. The fecal K concentration of hemodialysis
      patients was increased significantly(p < 0.01) compared to that of healthy
      subjects. The K-flux activity of erythrocytes and the serum K concentration
      correlated negatively(r = -0.482, p < 0.01) in non-diabetic hemodialysis
      patients, but did not correlate in diabetic hemodialysis patients. K-flux
      activity and Kt/V for urea correlated significantly(r = 0.412, p < 0.05). The K
      flux activity of erythrocytes collected after hemodialysis therapy significantly
      increased (p < 0.05) compared with that of erythrocytes collected before therapy.
      We speculated that the K-flux activity of various cells including erythrocytes
      participates in the regulation of serum K in hemodialysis patients and that the
      inhibitory factors on K-flux activity are removed partially by hemodialysis
      therapy.

PMID- 11307321
TI  - [PTH and bone metabolism in chronic dialysis patients].
AB  - The abnormal metabolism of calcium and bone is one of the most common
      complications seen in chronic dialysis patients. The activity of PTH has been
      mainly assessed by intact PTH assay; however, recent data suggest that this assay
      may overestimate PTH activity by detecting 7-84 PTH fragments in addition to 1-84
      PTH molecules(whole PTH). Another issue in this field is that higher levels of
      PTH are needed to maintain normal bone turnover in uremic patients. Accumulated
      osteoprotegerin in uremic serum may be responsible for this skeletal resistance
      to PTH.

PMID- 11307322
TI  - [Pathophysiology of blood pressure variability in patients with chronic renal
      failure under maintenance hemodialysis].
AB  - The rise of blood pressure is negatively related with the glomerullar filtration
      rate(GFR) in patients with terminal renal failure. Hypertension may be a
      mechanism to maintain renal blood flow and GFR constant by the increased driving
      force of blood to the kidney. Elevated levels of a so-called third factor, now
      designated as endogenous digitalis, are found in those patients. The most likely
      candidate of the endogenous digitalis is ouabain, which causes hypertension with
      chronic administration. On the other hand, extreme hypotension often occurs
      during maintenance hemodialysis, and since hemodynamic alterations closely
      resemble endotoxin shock, the involvement of nitric oxide(NO) over-production has
      been suggested. When we measured nitrate anion as the final metabolite of NO, the
      concentration was significantly higher in patients with marked hypotension during
      hemodialysis than those without hypotension. Since reflex tachycardia was not
      observed during hypotension, we speculated that those patients had autonomic
      disturbances, and assessed autonomic function by heart rate spectral analysis.
      Although the high frequency spectral power, regarded as the vagal tone, was not
      significantly different between the groups, low/high frequency spectral power
      ratio, which was thought to be a sympathetic component, was significantly lower
      in patients with hypotension during hemodialysis than that in patients without
      hypotension. We speculated that NO synthase may be induced by the stimuli to
      monocytes by tubes and dialyser membrane made of synthetic materials leading to
      the over production of NO during and after regular hemodialysis. Thus, cytokines
      may be the mediator of the induction of NO synthase. Dilated capacitance vessels
      decrease the venous return to the heart, which may be the direct cause of
      dialysis-induced hypotension.

PMID- 11307323
TI  - [Beta 2-microglobulin and dialysis-related amyloidosis].
AB  - Dialysis-related amyloidosis is a common complication encountered in patients
      receiving chronic hemodialysis. beta 2-microglobulin(beta 2-m) constitutes the
      causative protein of amyloidosis, and its deposition in tissues has been proven
      to be a primary cause of the onset. However, many other risk factors are also
      associated including (1) prolonged duration of dialysis, (2) advanced age, (3)
      dialysate of low purity, and (4) the use of a dialysis membrane with poor
      biocompatibility. Recently we confirmed that apolipoprotein E is a risk factor
      for the onset of carpal tunnel syndrome associated with dialysis-related
      amyloidosis. Dialysis using high-flux membranes and the clinical application of a
      column that selectively adsorbs beta 2-m are currently being assessed interms of
      the ability to remove as much beta 2-m from the blood as possible. Drug therapy
      may also be useful at present in symptomatic treatment; a low dose of
      adrenocorticosteroids has recently been demonstrated as extremely effective for
      joint pain associated with beta 2-m amyloid deposits. The long-term use of drugs,
      however, carries a risk of side effects. As a therapeutic approach to dialysis
      related amyloidosis, high-flux dialysis membranes permitting the elimination of
      beta 2-m with satisfactory biocompatibility have been developed and positive
      clinical effects have been observed both in the retrospective and prospective
      studies in the use of high-flux membranes together with a decrease in the serum
      beta 2-m level. However, there is no evidence yet of the long term reduction of
      amyloid deposits when the elimination of beta 2-m is maintained using a high-flux
      membrane.

PMID- 11307324
TI  - [Viral hepatitis in hemodialysis patients].
AB  - Hemodialysis patients are one of the high-risk groups for viral hepatitis,
      especially hepatitis C virus(HCV) infection. Although using recombinant human
      erythropoietin to treat anemia and introducing HCV testing of donated blood have
      been expected to reduce the incidence of HCV infection, occasional transmission
      of HCV to hemodialysis patients still occurs. The epidemiological and
      phylogenetic analysis provides the evidence for nosocomial infection of HCV in
      hemodialysis units. On the other hand, the discrepancy between results of anti
      HCV antibody and HCV RNA is observed in some hemodialysis patients, indicating
      that the isolation of patients positive for anti-HCV antibody is not effective
      for the prevention of transmission of HCV. The strict enforcement of universal
      precaution such as carefully changing gloves should be more important for the
      prevention of nosocomial infection.

PMID- 11307325
TI  - [New techniques and laboratory examinations in the detection and evaluation of
      hypertension].
AB  - Monitoring of 24-hour ambulatory blood pressure(ABPM), measurements of
      circulating vasoactive substances and microalbuminuria, and assessment of gene
      polymorphisms as genetic markers are introduced to detect and evaluate
      hypertension. Classifications of ABPM based on impact on risks of cardiovascular
      diseases have been currently available. Plasma level of brain natriuretic
      peptide(BNP), a cardiac hormone, increases markedly in congestive heart failure,
      in proportion to its severity, and is evaluated as a potential index of severity
      of heart failure. In addition, serum level of hepatocyte growth factor(HGF), a
      member of endothelium specific growth factors, in hypertension might be useful
      for evaluating the presence of complications and degree of endothelial
      dysfunction. In diabetes mellitus, onset of microalbuminuria appeared as an
      important sign of early nephropathy. There is growing evidence that
      microalbuminuria is an independent predictor of atherosclerosis and premature
      death in the general population. Current studies have shown that gene
      polymorphisms including components of the renin-angiotensin-aldosterone system
      may be possible genetic markers for hypertension and its associated
      cardiovascular diseases. Our data suggest positive linkages between hypertension
      and 4 gene polymorphisms including angiotensinogen Met235Thr, angiotensin
      converting enzyme I/D, aldosterone synthase CYP11B2 T-344C, and endothelial
      nitric oxide synthase Glu298Asp in the Aomori population.

PMID- 11307326
TI  - [Diagnostic test approved by Ministry of Health and Welfare (February 2001)].

PMID- 11307328
TI  - [Informed consent for the use of the remaining portion of laboratory specimens
      for education, research, and quality control of laboratory tests].
AB  - The remaining portion of a laboratory specimen is usually used for education,
      research, and quality control of laboratory tests in hospitals, but informed
      consent has not been obtained because of the high volume of patients who undergo
      laboratory tests. However, patients must be informed in some manner. Therefore,
      we decided to inform patients that any remaining specimen would be used for
      various purposes by placing such a notice on walls in the central clinical
      laboratory and hospital lobby. We then obtained a signature on a dissent
      document, instead of a consent document, from any patient who dissented from such
      use. This indirect process for obtaining informed consent was approved by the
      ethics committee of Osaka University Medical School. The number of dissent
      documents sent in to the director was 54 of about 400,000 patients who underwent
      laboratory tests over the last 3 years, and there was no complaint against this
      "informed consent process".

PMID- 11307327
TI  - [Identification of microbial subtypes from antibiotic susceptibility data in
      clinical laboratory for nosocomial infection surveillance].
AB  - We developed an algorism to identify microbial subtypes automatically from daily
      antibiotic susceptibility data in clinical microbiology laboratory. The
      susceptibility pattern was expressed as a string of digits, each consisting of
      0(resistant), 1(intermediate) or 2(susceptible) to respective antibiotics. Any
      two patterns were regarded identical and combined if the difference at each digit
      never exceeds 1. The combined pattern was expressed as an array of digit-by-digit
      weighted averages of the two. The second combination was based on a degree of
      similarity among the numerical patterns using a formula, which was designed to
      emphasize differences in highly variable elements. This subgrouping procedure was
      done every three months. Identity of the detected subtypes between the intervals
      was determined using the same algorism as for the second combination. The
      algorism was applied to data of clinical isolates of MRSA, Pseudomonas aeruginosa
      (PA), Klebsiella pneumoniae (KP), Enterococcus faecalis (EF), Streptococcus
      pneumoniae (SP), Escherichia coli (EC) that were obtained over a period of 4
      years. Three major subtypes of MRSA, KP and EF were consistently detected with
      shifting mutual frequencies. Most of EC isolates belonged to two consistent
      subtypes. Although PA and SP had one or two consistent subtypes, there were
      multiple minor subtypes of varying frequencies. This analysis is regarded as an
      "infotyping", in contrast to serotype or genotype, of clinical microbial
      isolates, which is useful for nosocomial infection surveillance.

PMID- 11307329
TI  - [Extraction of RNA from paraffin embedded tissues and analysis of p53 gene
      expression in colonic cancer].
AB  - We examined, immunohistochemically and molecular biologically, p53 gene
      expression in 10 patients with colonic cancer. RNA was extracted from paraffin
      embedded normal and colonic cancer tissues by using RNA isolator kit and
      proteinase K. The most effective time and concentration of proteinase K for RNA
      extraction was 24 hours and 100 micrograms/ml, respectively. P53 gene expression
      was analyzed by ABI PRISM 7700 Sequence Detection System(ABI 7700 System,
      Perkinelmer). Gene expression level in each sample was estimated on the basis of
      the standard curve of ABI 7700 System. Human G3PDH gene was used as the internal
      control. Immunohistochemically, the tumor cells in all examined cases showed a
      strong positivity for anti-p53 gene antibody. In ABI 7700 System, expression of
      p53 gene in the malignant tissues revealed a high level in only 2 cases that had
      a clinical stage IV, however, in remaining 8 cases a clinical stage was I to III
      and expression level of p53 was relatively lower. These results suggest that
      colonic cancer cells show mutant-p53 gene expression, and a ratio of mutant- to
      wild-p53 gene may have something to do with a relationship between gene
      expression and clinical stage.

PMID- 11307330
TI  - [Clinical significance of a new fibrinogen/fibrin degradation products(FDP) test
      using plasma samples for the diagnosis of fibrinogenolysis and fibrinolysis].
AB  - Recently, a new fibrinogen/fibrin degradation products(FDP) test using monoclonal
      antibodies against FDP(LPIA FDP-P: FDP-P) has been developed, which is able to
      measure FDP directly in plasma. The objective of this study is to clarify
      clinical significance of the test in the diagnosis of fibrinogenolysis and
      fibrinolysis in comparison with a conventional FDP test using polyclonal
      antibodies against fibrinogen(FDP-S) and D-dimer test using monoclonal antibodies
      against D-dimer(D-D). The monoclonal antibodies used in FDP-P test was shown to
      recognize fragment X, Y and D1 derived from fibrinogen digested by urokinase, and
      was also to recognize XDP fragments, D-dimer and D derived from cross-linked
      fibrin digested by tissue plasminogen activator using SDS-PAGE and immunoblotting
      analysis. There was a good correlation of FDP levels between FDP-P test and FDP-S
      test. However, levels of FDP in both tests were discrepant in several samples.
      There was a tendency that the levels of FDP were higher in FDP-S test than in FDP
      P test. Such discrepancy was suggesting that soluble fibrin monomer complex(FM)
      was recognized by the antibodies used in FDP-S test, but not recognized by the
      antibodies used in FDP-P test. There was also a good correlation of FDP levels
      between FDP-P test and D-D test. However, the levels of FDP in both tests were
      discrepant in several samples. The levels of FDP were higher in FDP-P test than
      in D-D test. These discrepant samples had lower levels of antiplasmin and higher
      levels of plasmin antiplasmin complex(PIC), and also showed XDP fragments, D
      dimer, X, Y, and D1 by using SDS-PAGE. These observations suggest that D-D test
      measures only fibrinolytic fragments, while FDP-P test measures fibrinogenolytic
      fragments as well as fibrinolysis. In results, the FDP-P test was confirmed to be
      a useful tool to examine fibrinogenolysis as well as fibrinolysis more
      specifically than the conventional FDP test.

PMID- 11307333
TI  - [Hypertension in medicine and medical care in Japan].

PMID- 11307331
TI  - [A case of primary HIV infection with oral candidiasis not diagnosed by western
      blot].
AB  - Seroconversion to human immunodeficiency virus(HIV) associated with an illness
      characterized by fever, sore throat, and lymphadenopathy, sometimes with rash,
      diarrhea, and vomiting. Leukopenia and liver dysfunction also can occur in some
      patients. The antibody response associated with HIV infection is directed against
      a variety of viral proteins. Western blot analysis(WB) is used currently for
      determining HIV-1 infection. A 47-year-old man whose wife was infected with HIV
      was found to have contracted primary HIV infection. His first HIV antibody
      examination 4 weeks after speculated exposure was negative by particle
      agglutination(PA) method and WB. Approximately 2 weeks later he experienced
      fever, general fatigue, oral candidiasis. His second laboratory examination
      showed positive PA and indeterminate WB tests, an HIV-RNA PCR of 4.4 x 10(5)
      copies/ml, 223 CD4+ lymphocytes/microliter, and liver dysfunction. Two weeks
      later, all of his symptoms and the abnormal lab data had improved with antifungal
      therapy alone and no anti-HIV therapy. Subsequently, it took 16 more weeks before
      HIV infection could be diagnosed by WB. It is necessary to adopt an appropriate
      HIV-1 PCR method to shorten the diagnostic window in primary HIV infection.

PMID- 11307334
TI  - [Challenge to the 21st century--the age of globalization for the new century:
      training of truly professional internists].

PMID- 11307335
TI  - [Physiopathology and treatment of chronic viral hepatitis].

PMID- 11307336
TI  - [Physiopathology and treatment of refractory anemia].

PMID- 11307337
TI  - [Molecular mechanism involved in arteriosclerosis--the roles of nitric oxide and
      Rho/Rho-kinase].

PMID- 11307338
TI  - [Physiopathology and treatment of glomerulonephritis].

PMID- 11307339
TI  - [Physiopathology and treatment of the acute stage of cerebral infarction].

PMID- 11307340
TI  - [Angiitis syndrome--from the analysis at a molecular level to clinical studies].

PMID- 11307341
TI  - [Emerging and re-emerging infections].

PMID- 11307342
TI  - [Life style-related diseases--from the etiological mechanism to prevention].

PMID- 11307343
TI  - [Internal medicine for the new century--from medical science to medical care].

PMID- 11307344
TI  - [A 63-year-old woman following valve replacement--blood coagulation and
      hemorrhage].

PMID- 11307345
TI  - Relationship between mouth breathing and postural alterations of children: a
      descriptive analysis.
AB  - The research within this article seeks to verify and demonstrate the consequences
      of mouth breathing versus nasal respiration and to view supposed postural
      alterations in groups of children within specific age ranges. The authors state
      that children with nasal respiration, age 8 and above, present with better
      posture than those who continue oral breathing beyond age 8. The importance of
      picture documentation is stressed in order to provide the most information
      regarding postural changes. A review of research and literature is provided in
      the article.

PMID- 11307346
TI  - The development of normal feeding and swallowing: Showa University study of the
      feeding function.
AB  - Since the 1980s the Department of Hygiene and Oral Health at the Showa University
      School of Dentistry has focused its research efforts on the development of
      feeding function and disorders. In addition, we have treated dysphagic children
      and dysphagic elderly using our feeding training program approach. The
      developmental course of the feeding function includes the following steps: 1)
      Suckle feeding and prefeeding period; 2) Acquiring the ability to swallow with
      lips closed; 3) Acquiring the ability to take food with lips closed; 4) Acquiring
      the ability to push mashed food with the tongue and anterior hard palate; 5)
      Acquiring the ability to perform mastication; 6) Beginning self-feeding; 7)
      Beginning finger feeding; 8) Beginning using table ware.

PMID- 11307347
TI  - Assessment of the development of hand and mouth coordination when taking food
      into the oral cavity.
AB  - The purpose of this study was to establish an assessment method for evaluation of
      hand and mouth coordination during self-feeding. The subjects were four normally
      developed infants. Their feeding behavior was videotaped at two or four week
      intervals (from age eight months to thirty-six months). The items analyzed were
      nine viewpoints for finger feeding and eight viewpoints for spoon-feeding. The
      results obtained included: finger feeding--development of cylinder and pinch
      grasp, two patterns of hand in relation to neck and trunk, placement of food into
      the mouth, developmental aspects of neck rotation when taking food with the lips;
      spoon feeding--holding technique, flexion of elbow and shoulder, taking food from
      the spoon bowl by the lips, patterns of neck rotation. From the results of these
      observations, we conclude that the items analyzed in this study can be useful for
      the assessment of the developmental process of hand and mouth coordination in
      self-feeding.

PMID- 11307348
TI  - Tongue lip and jaw differentiation and its relationship to orofacial
      myofunctional treatment.
AB  - A number of developmental changes occur in eating patterns from infancy through
      childhood. Initially a primitive reflexive process, deglutition develops into a
      complex, integrated voluntary/reflexive process. The movements of the tongue,
      lips and mandible are easily observed to undergo a transformation from
      synergistic, undifferentiated movements in the infant, to differentiated and
      refined movements required for biting, chewing, bolus formation and propulsion in
      the toddler and young child. This transformation is also crucial for the
      development of higher levels of articulatory precision and coordination required
      for verbal communication. This developmental process does not always occur in
      individuals exhibiting orofacial myofunctional disorders. This article will
      review current research in this area as well as describe how to evaluate for
      normal tongue, lip and jaw differentiation, and present exercises to develop
      these skills, which are necessary for successful outcomes in orofacial
      myofunctional treatment.

PMID- 11307349
TI  - The speech pathology treatment with alterations of the stomatognathic system.
AB  - This article analyzes differences in orthodontic and craniofacial classifications
      and the role of the speech-language pathologist in adequately treating those
      patients with varying Class II and Class III malocclusions. Other symptoms, such
      as those of mouth breathing and tongue position, are compared and contrasted in
      order to identify characteristics and treatment issues pertaining to each area.
      The author emphasizes a team approach to myofunctional therapy and stresses the
      importance of collaborative treatment.

PMID- 11307350
TI  - Case presentation: resolution of an oral lesion as a result of orofacial
      myofunctional therapy.
AB  - This case presentation examines the etiology, evaluation and treatment of a 57
      year-old-female presenting with an area of irritation/chronic lesion on the
      anterior lingual surface. Orthodontic history and lingual and labial postures are
      discussed.

PMID- 11307351
TI  - Mastication in the oral myofunctional disorders.
AB  - The aim of this article is to show two ways of clinical work with mastication in
      Oral Myofunctional Disorders. Consideration is given to limitations that make
      direct treatment impossible: symptoms/signs of temporo-mandibular joint,
      occlusions alterations, types of orthodontics or orthopedics appliances and
      loosing teeth. The procedures suggested are named procedures WITH and WITHOUT
      LIMITATIONS.

PMID- 11307352
TI  - [World's mental health day in 2001 focuses on destigmatization].

PMID- 11307353
TI  - [Current treatment of psychosis].

PMID- 11307354
TI  - [Reactions to mental stress].

PMID- 11307355
TI  - [Discovering depression].

PMID- 11307356
TI  - [Is prevalence of depression overestimated?].

PMID- 11307357
TI  - [Current drug treatment. Effects of antidepressive agents in nervous and stress
      related disorders].
AB  - Antidepressants have a much broader range of indication than the name suggests.
      The efficacy of antidepressant treatment of nervous and stress-related disorders
      has been documented in several controlled trials, both in comparison with placebo
      and with other antidepressants. Most studies have included testing in panic
      disorder, with or without agoraphobia, and obsessive compulsive disorder, but
      there is empirical evidence for the efficacy of the drugs in most anxiety
      disorders. Antidepressants with a preference for serotonergic neurotransmission
      (i.e. clomipramine and SSRIs (serotonin specific reuptake inhibitors) are
      particularly effective in the treatment of panic disorder and obsessive
      compulsive disorder. Owing to their more favourable side effect profile as
      compared with classical antidepressants, the SSRIs are considered to be the drugs
      of first choice, except for generalised anxiety disorder, where the efficacy of
      venlafaxine has been most thoroughly documented. Studies comparing different
      antidepressant are warranted. So are studies elucidating the relative benefits of
      drug treatment and psychotherapy, but, with the concept of modern anxiety
      treatment, there is no principal objection to combining the two treatment
      methods.

PMID- 11307358
TI  - [Reactions to torture and persecution. Traumatized refugees in the Danish health
      service].
AB  - The Danish health services encounter a growing number of refugees who suffer from
      the effects of persecution and torture. To be a traumatised refugee in a foreign
      culture often causes psychological reactions and biological changes, and, at the
      same time, adaptation to a new culture is a demanding existential challenge. The
      condition is rather poorly described by the diagnoses "post-traumatic stress
      disorder" and "enduring personality change after catastrophic experience". These
      conditions can cause difficulties both diagnostically and treatment-wise, as the
      trauma story can awaken violent reactions in the doctor, and because the symptoms
      can be so culturally framed they are difficult to interpret. The prognosis
      depends on a number of issues pertaining to the patient, the trauma, and the
      patient's overall state after the trauma. At best, the prognosis is relatively
      good, but in a number of cases the patient's state becomes chronic and disabling.
      At present, the recommended treatment is a combination of psychotherapy,
      psychopharmacological treatment, physiotherapy, and social initiatives. There is
      still uncertainty as to the optimal treatment, and the organisational situation
      regarding treatment in Denmark is unclear.

PMID- 11307359
TI  - [From evidence to tobacco policy--health policy analysis].

PMID- 11307360
TI  - [Psychiatric diagnoses and treatment with psychopharmaceuticals. Guidelines from
      the National Board of Health and Welfare].

PMID- 11307361
TI  - [The eight's decade--heart massage--no, thank you].

PMID- 11307362
TI  - [Statins. A new osteoporosis prophylaxis?].

PMID- 11307363
TI  - [Therapeutic monitoring by blood concentrations with the focus on cyclosporin A].
AB  - Cyclosporin A therapeutic drug monitoring with through concentrations results in
      a high frequency of toxicity or therapeutic failure. There is no simple relation
      between the through and the mean concentration, and thus the therapeutic effect.
      Estimation of the AUC on sparse sampling or population pharmacokinetic analysis
      and the Bayesian fit of the parameters are discussed.

PMID- 11307364
TI  - [Clozapine-induced toxic hepatitis].
AB  - A case of clozapine-induced toxic hepatitis in a 49-year old woman with
      schizophrenia is described. The daily clozapine dose was clinically titrated to
      300 mg. Subsequently, the patient experienced lethargy and anorexia, and fever,
      eosinophilia, leucocytosis and abnormal liver parameters were found. The serum
      concentration of clozapine was 8595 nmol/l, and treatment was discontinued. After
      eight days, the condition stabilised, and low-dose clozapine treatment was
      successfully reinstituted with serum monitoring (TDM).

PMID- 11307365
TI  - Diagnosis of infection in sepsis.

PMID- 11307366
TI  - Immunological therapy of sepsis: experimental therapies.

PMID- 11307367
TI  - Other supportive therapies in sepsis.
AB  - Patients who survive the circulatory and organ deficits in sepsis may still fall
      victim to complications such as pulmonary embolism and stress ulcer bleeding.
      Although there is no clearcut evidence to quantitate the impact of such
      complications on mortality, the anticipated impact is grave when considering the
      compromised physiological reserve of these patients. For this reason it is
      important to institute effective prophylaxis to minimize the impact. In addition,
      catabolism associated with sepsis likely influences the recovery of patients with
      sepsis and moreover can compromise the response of the immune system against an
      infectious insult. Early and adequate nutritional support therefore appears
      important. There is much controversy and lack of prospective research regarding
      effect of supportive therapies on outcome in patients with severe sepsis. This
      research is needed.

PMID- 11307368
TI  - Definition of sepsis.

PMID- 11307369
TI  - Antibiotics in sepsis.

PMID- 11307370
TI  - Source control in the management of sepsis.
AB  - The process of surgical decision making is based on both general principles that
      are amenable to evaluation using rigorous techniques of clinical research and the
      intangible element of surgical judgment that seeks to apply those principles to
      the care of an individual patient. The role of surgical judgment is inescapable,
      even though it is intrinsically subjective and recalcitrant to objective
      evaluation, for a host of factors modify the application of principle in each
      patient, and render the circumstances of a given problem sufficiently
      distinctive, that evidence must be tempered with common sense. We have tried to
      provide, through an evidence-based approach to a series of questions, the
      rationale for the basic principles that should guide the clinician in initiating
      or modifying source control, recognizing that sound clinical judgement demands,
      at times, that these be set aside. In the individual patient, evidence of
      clinical improvement is the most important marker of the approach selected.
      Evaluation of the adequacy of source control in the critically ill patient can be
      difficult. As with other modes of anti-infective therapy, effective source
      control measures are expected to result in clinical improvement, reflected in:
      Resolution of clinical signs of sepsis or systemic inflammation. Bacteriological
      resolution. Evidence of reversal of the metabolic sequelae of infection, with
      normal progression of wound healing, reflected in the formation of granulation
      tissue, and epithelialization. Radiographic evidence of control of an infectious
      focus. Prevention of further organ dysfunction, and resolution of existing organ
      dysfunction. Survival. Evaluation of the adequacy of source control may
      necessitate planned reoperation. The adequacy of debridement of necrotizing soft
      tissue infections can be assessed by repeat exploration under general anesthesia,
      continuing the process until there is evidence of healthy granulation tissue
      throughout the wound. Planned reexploration is also indicated for patients with
      diffuse intestinal ischemia to ensure bowel viability. The appropriate
      interventions to determine the adequacy of source control are dictated by the
      clinical circumstances. A residual or recurrent abscess can usually be
      demonstrated by CT or ultrasound examination, while resolution of an abscess
      cavity can be monitored using sinograms. The diagnosis of persistent or evolving
      tissue necrosis is guided by the clinical setting. Retroperitoneal necrosis can
      be detected by CT, while sigmoid ischemia following aortic aneurysmectomy can be
      evaluated by sigmoidoscopy. Occasionally diagnostic peritoneal lavage assists in
      establishing a diagnosis of gut ischemia; the lavage fluid appears bloody with
      established ischemia. The diagnosis of an infected foreign body requires an
      appropriate history and is supported by recurrent bacteremia or by positive
      cultures drawn retrograde through an indwelling vascular or peritoneal dialysis
      catheter. Finally, ongoing contamination from a breach of the gastrointestinal
      tract can be documented by appropriate contrast studies. The general principles
      that guide the use of source control techniques in the management of the patient
      with severe sepsis or septic shock are readily articulated. Their implementation
      in practice, however, is more complex, and does not, as a rule, lend itself to
      simple algorithms that are applicable in all cases. Moreover evidence-based
      support for these principles is weak. In the final analysis, the elusive process
      of experienced surgical judgement is invaluable for all but the most
      straightforward problems.

PMID- 11307371
TI  - Airway and lung in sepsis.

PMID- 11307372
TI  - Hemodynamic support in septic shock.

PMID- 11307373
TI  - Immunological therapy in sepsis: currently available.

PMID- 11307374
TI  - Aetiology of root canal treatment failure: why well-treated teeth can fail.
AB  - LITERATURE REVIEW: Root canal treatment usually fails when the treatment is
      carried out inadequately. However, there are some cases in which the treatment
      has followed the highest standards yet still results in failure. In most of the
      cases, the endodontic failure results from persistent or secondary intraradicular
      infection. Extraradicular infections may also be implicated in the failure of
      some cases. In addition, it has been claimed that a few cases can fail because of
      intrinsic or extrinsic nonmicrobial factors. The purpose of this paper is to
      discuss the aetiology of the failure of root canal treatment, particularly in
      cases of well-treated root canals. Indications for the treatment of endodontic
      failures are also discussed.

PMID- 11307375
TI  - Expression of beta 1 integrins in human dental pulp in vivo: a comparative
      immunohistochemical study on healthy and chronic marginal periodontitis samples.
AB  - AIM: The objective of this study was to determine the tissue distribution of beta
      1 integrin chains in sound human dental pulps and to compare the findings with
      connective tissue compartments of other organs and to pulp tissue in teeth
      extracted due to periodontal disease. METHODOLOGY: Freshly frozen pulp tissue
      samples from teeth extracted for orthodontic reasons were examined and compared
      to samples from teeth extracted due to chronic (marginal) periodontitis. beta 1
      integrin chains were determined using an indirect-immunoperoxidase technique.
      Seven monoclonal antibodies recognizing alpha 1, alpha 2, alpha 3, alpha 4, alpha
      5, alpha 6 and beta 1 chains of Very Late Activation Antigen (VLA) integrins were
      used for this purpose. RESULTS: VLA-1, VLA-2, VLA-3 and VLA-5 were expressed by
      vascular endothelium and vascular smooth muscle in varying intensities in both
      groups. VLA-6 reactivity was observed in the basal surfaces of arterial, venous
      and capillary endothelia. Our results indicate that there was no significant
      difference in the expression of VLA integrins in sound pulp tissue when compared
      to the samples from chronic (marginal) periodontitis and the connective tissue
      compartments of other viscera. CONCLUSION: The present findings suggest that
      human dental pulp tissue is not different from other connective tissue
      compartments in the body with respect to VLA integrin expression, and chronic
      marginal periodontitis does not affect pulp tissue to a histopathologically
      detectable extent.

PMID- 11307376
TI  - A study of endodontic treatment carried out in dental practice within the UK.
AB  - AIM: The purpose of this study was to gather both qualitative and quantitative
      information on the nature of root canal treatment carried out by a group of
      dentists working within the United Kingdom. METHODOLOGY: A two-part questionnaire
      was posted to 720 dentists who graduated from the Dental School, Cardiff, Wales,
      UK. The first part requested basic information regarding age, year of
      qualification, field of practice, etc. The second part consisted of 15 questions
      on endodontic practice and root canal treatment. RESULTS: The response rate was
      41.5%. Two hundred and ninety-nine questionnaires contained useful information.
      The majority of practitioners did not use rubber dam during root canal treatment.
      The vast majority (89%) exposed a radiograph with an instrument of known length
      in situ to gauge the 'working length', a small number relied upon tactile
      sensation. Most practitioners used local anaesthetic solution as an irrigant
      during instrumentation of the root canal. A wide variety of instruments were used
      for root canal treatment; a stepback technique was preferred by almost half the
      practitioners. Antiseptic solution was preferred as an interappointment dressing.
      More than half of the respondents used laterally condensed gutta-percha to
      obturate root canals in anterior teeth but only one-third used the same technique
      in posterior teeth. Less than half the respondents exposed a radiograph to check
      the fit of the master point prior to obturation. Two-thirds of practitioners used
      a zinc oxide based material as their root canal sealer. Three-quarters of the
      practitioners exposed a post obturation radiograph. CONCLUSIONS: The results of
      this study suggest that although some dentists are using the techniques taught
      during their undergraduate careers, a large percentage now use techniques with no
      evidence of clinical effectiveness.

PMID- 11307377
TI  - Dimensional variability of nonstandardized greater taper finger spreaders with
      matching gutta-percha points.
AB  - AIM: The purpose of this research was to determine the compatibility and
      dimensional variability between nonstandardized gutta-percha points and matching
      finger spreaders. METHODOLOGY: The diameters of nonstandardized gutta-percha
      points (n = 15) and matching finger spreaders (n = 15) from different
      manufacturers (Kerr, Dentsply Maillefer, Vereignigte Dentalwerke and Roeko) were
      determined and statistically analysed using a profile projector under a
      magnification of 50 x (+/- 0.002 mm). RESULTS: The dimensions of the finger
      spreaders and gutta-percha cones were inconsistent. Of the 29 groups of
      nonstandardized gutta-percha cones evaluated, 22 had standard deviations larger
      than 0.020 at D1. The standard deviations at D11 were greater than at D1, with
      the exception of those manufactured by Roeko. Overall, nonstandardized gutta
      percha cones made by VDW had the greatest dimensional consistency within each
      size group; the largest variations were seen in the Dentsply Maillefer gutta
      percha points. The 13 sizes of nonstandardized finger spreaders were more
      consistent. CONCLUSIONS: The results of this study show that corresponding sizes
      of nonstandardized finger spreaders and gutta-percha cones have statistically
      significant differences. There were large dimensional variations within sizes and
      discrepancies between the nominal size and actual size. Thus, these discrepancies
      may cause problems during root canal filling.

PMID- 11307378
TI  - Digitization, analysis and processing of dental images during root canal
      preparation with Quantec Series 2000 instruments.
AB  - AIM: The aim of this study was to determine the shaping ability of Quantec Series
      2000 nickel-titanium instruments in the mesio-buccal roots of maxillary first
      molars and the mesial roots of mandibular first molars. METHODOLOGY: A total of
      20 canals were prepared with Quantec instruments, adopting the technique
      recommended by the manufacturer. Each canal was sectioned horizontally into four
      and the canal in each portion photographed before and after preparation. The
      images obtained were digitized and the increase in canal surface for each
      quadrant of the four sections was evaluated, along with the variation in centre
      of mass after instrumentation. RESULTS: Mechanical instrumentation of the canals
      generated mean centre of mass displacements that did not vary between sections,
      except for the mid-apical section, which showed significant mesial displacement,
      i.e. toward the side opposite the furcation. Thus, overall, the widening of the
      canal was symmetrical. CONCLUSIONS: Under the conditions of the study, the
      Quantec Series 2000 rotary system was simple and safe to use, and created good
      three-dimensional mechanical preparation of natural canals.

PMID- 11307379
TI  - An in vitro study into the effect of the ferrule preparation on the fracture
      resistance of crowned teeth incorporating prefabricated post and composite core
      restorations.
AB  - AIM: This in vitro study investigated the effect of a ferrule preparation on the
      fracture resistance of crowned central incisors incorporating a prefabricated
      post (Parapost) cemented with Panavia-Ex and with a composite core. METHODOLOGY:
      The test group consisted of 10 post crowned natural central incisor teeth with a
      2-mm wide ferrule preparation, whilst the control group of 10 teeth had no
      ferrule. The specimens were mounted on a Lloyd universal testing machine and a
      compressive load was applied at an angle of 135 degrees to the palatal surface of
      the crown until failure occurred. RESULTS: In both groups, failure occurred at
      higher loads compared with previous studies. The mean failure load was 1218 N for
      the unferruled group and 1407 N for the ferruled group. Statistical analysis
      showed no significant difference between the groups. CONCLUSIONS: Under the
      conditions of this study, when composite cement and core materials are utilized
      with a Parapost prefabricated system in vitro the additional use of a ferrule
      preparation has no benefit in terms of resistance to fracture.

PMID- 11307380
TI  - Influence of rotational speed, torque and operator's proficiency on ProFile
      failures.
AB  - AIM: The purpose of this study was to evaluate the influence of rotational speed,
      torque, and operator experience with a specific Ni-Ti rotary instrumentation
      technique on the incidence of locking, deformation and separation of instruments.
      METHODOLOGY: ProFile Ni-Ti rotary instruments (PRI) sizes 40-15 with a 6% taper
      were used in a crown-down technique. In one group of canals (n = 300) speeds of
      150, 250 and 350 rpm (subgroups 1, 2 and 3) were used. Each one of the subgroups
      included 100 canals. In a second group (n = 300) torque was set at 20, 30 and 55
      Ncm (subgroups 4, 5 and 6). In the third group (n = 300) three operators with
      varying experience (subgroups 7, 8 and 9) were also compared. Each subgroup
      included the use of 10 sets of PRI and 100 canals of extracted human molars. Each
      set of PRI was used in up to 10 canals and then sterilized before each case.
      NaOCl 2.5% was used as an irrigant. The number of locked, deformed, and separated
      instruments for the different groups, and within each part of the study was
      analysed statistically for significance with chi-squared tests. RESULTS: In group
      1 only one instrument was deformed in the 150-rpm group and no instruments
      separated or locked. In the 250-rpm group instrument separation did not occur,
      however, a high incidence of locking, deformation and separation was noted in the
      350-rpm group. In general, instrument sizes 30-15 locked, deformed and separated.
      Chi-squared statistics showed a significant difference between the 150 and 350
      rpm groups but no difference between the 150 and 250 rpm groups with regard to
      instrument separation. Overall, there was a trend toward a higher incidence of
      instrument deformation and separation in smaller instruments. Locking and
      separation occurred during the final passage of the instruments, in the last
      (tenth) canal in each subgroup. In the second group, neither separation nor
      deformation and locking occurred during the use of the ProFile instruments, at
      150 rpm, and at the different torque values. In the third group, chi-squared
      analysis demonstrated that significantly more instruments separated with the
      least experienced operator. Instrument locking, deformation, and separation did
      not occur with the most experienced operator. CONCLUSIONS: Preclinical training
      in the use of the PRI technique with crown-down at 150 rpm were crucial in
      avoiding instrument separation and reducing the incidence of instrument locking
      and deformation.

PMID- 11307381
TI  - A survey of interfacial forces used during endosonic instrumentation of root
      canals.
AB  - AIM: The aim of this in-vitro study was to measure interfacial forces acting
      between root canal dentine and ultrasonic files during endosonic instrumentation.
      METHODOLOGY: Single-rooted teeth were mounted on a cantilevered aluminium beam to
      which two pairs of single element strain gauges were joined in a half-bridge
      configuration mounted at right angles to each other. The strain gauges were
      connected to an analogue-to-digital converter fitted in a microcomputer via a
      conditioning amplifier. This enabled strains to be recorded as a function of
      interfacial forces over a period of time. Twenty operators instrumented root
      canals using sizes 15, 20 and 25 ultrasonically energized K-type files. The
      lateral forces generated were calculated. RESULTS: The mean interfacial forces
      used varied widely between operators and files, ranging from 18 g to 149 g, but
      there was a consistency in the relative magnitude for each operator. The average
      force used by the operators increased with file size; the differences between
      file sizes were significant (P < 0.05). CONCLUSIONS: The range of forces measured
      is broader than previously reported and may have a bearing on possible
      uncontrolled dentine removal, even during ultrasonically activated irrigation.

PMID- 11307382
TI  - The standardized-taper root canal preparation--Part 2. GT file selection and safe
      handpiece-driven file use.
AB  - AIM: To present guidelines on GT file selection, and safe operation. SUMMARY: It
      is not necessary to remove excessive dentine for effective root canal
      preparation. GT files allow safe, standardized preparation, and should be
      selected to fit the case in hand. Small Root canals should be prepared with 0.06
      and 0.08 taper GT files, whilst Large Root canals should be prepared with 0.10 GT
      or 0.12 Accessory GT files. The greatest challenge is un-learning habits acquired
      from traditional instrumentation methods. GT files should be used with light
      touch, and without up-down pumping motions. Spin speeds should be controlled
      below 300 r.p.m. for routine preparation. GT files are subject to fatigue and
      should be tracked to avoid overuse. It is recommended that GT files are discarded
      after the equivalent of five root canal preparations. For severe curvatures, GT
      files should be single-case tools. KEY LEARNING POINTS: The standard GT file set
      comprises three instruments of 0.06, 0.08 and 0.10 taper. All are size 20 at the
      tip, and have a maximum diameter of 1 mm. Accessory GT files have a standard
      taper 0.12, and maximum diameter of 1.5 mm. They are available in tip sizes 35,
      50 and 70. Large Roots are lower canines, upper anteriors, upper and lower single
      rooted premolars, palatal roots of upper molars and distal roots of lower molars.
      They should be prepared with 0.10 GT or 0.12 Accessory GT files. Small Roots are
      lower incisors, multirooted premolars, buccal roots of upper molars and mesial
      roots of lower molars. They should be prepared with 0.06 or 0.08 GT files. All GT
      files should be used with light force and at the correct spin speed. GT files
      should be discarded after the equivalent of five root canal uses.

PMID- 11307383
TI  - Calcium hydroxide in endodontic retreatment after two nonsurgical and two
      surgical failures: report of a case.
AB  - AIM: To describe the role of calcium hydroxide in infection control during
      complex endodontic retreatment. SUMMARY: A case is presented in which two
      conventional endodontic treatments and two surgical interventions failed to bring
      periapical healing. Despite this history, a further conventional treatment
      augmented by long-term disinfection with calcium hydroxide finally delivered a
      successful outcome. KEY LEARNING POINTS: Periapical healing follows proper
      intracanal infection control. Despite repeated surgical and nonsurgical
      intervention, careful retreatment can often bring healing. Calcium hydroxide has
      long-acting antimicrobial and soft-tissue dissolving activity. It is a helpful
      adjunct in endodontic retreatment.

PMID- 11307384
TI  - Bite force and occlusal load in healthy young subjects--a methodological study.
AB  - This study compares a new technique (Dental Prescale System) using pressure
      sensitive foils for recording of maximal jaw closing force with a conventional
      clinical measurement using a miniature force transducer in 17 students. For
      assessment of load distribution the "pressure" image was superimposed on
      digitiZed images of dental casts and compared with clinical registrations of
      tooth contact. The bite force recorded with foil was systematically higher than
      that recorded by conventional measurements. Further more teeth were assessed as
      being loaded than having clinical occlusal contact. The new technique seems
      promising, although time consuming.

PMID- 11307385
TI  - A comparison of the early postoperative care required by patients treated with
      single and two stage surgical techniques for the provision of Branemark implant
      supported mandibular overdentures.
AB  - Patients who underwent a single stage surgical procedure to place two Branemark
      implants to stabilise complete mandibular overdentures with bar attachments,
      required no more postoperative follow-up visits before definitive prosthesis
      construction than patients who had their implants placed at two separate surgical
      stages. However, the visits of the single stage group, occurred over a shorter
      time-scale and more attention was required to tighten or replace their healing
      abutments.

PMID- 11307386
TI  - Case report: aesthetic management of a localised periodontal defect with a
      gingival veneer prosthesis.
AB  - Traditionally acrylic resin gingival veneer prostheses have been used to disguise
      aesthetic deficiencies of maxillary anterior teeth following successful
      periodontal therapy and have been retained by engaging horizontal undercuts
      distal to the canine teeth. They are, however, versatile prostheses with uses in
      fixed and removable prosthodontics and therapeutic treatment of gingival
      conditions. In the case presented a small acrylic resin gingival veneer
      prosthesis retained by a resilient lining material was used to manage a localised
      periodontal defect of the mandibular central incisor teeth.

PMID- 11307387
TI  - Surface strains induced by measured loads on teeth in vivo: a methodological
      study.
AB  - Visual feedback enabled three subjects to apply predetermined near-axial loads to
      the incisal edge of an intact maxillary central incisor. In two subjects,
      principal strains and orientations developed on the labial surface of the intact
      incisor were resolved from strains recorded with a multiple element strain gauge.
      Load application was accurate and precise enough to allow resolution of strains
      induced by target loads of 10 to 50 N. Axially orientated compressive labial
      surface strains were induced by measured loads. The method could be used to
      validate bench-top stress analyses and investigate the effects of restoration on
      the structural integrity of teeth.

PMID- 11307388
TI  - Long-term experience with telescopically retained overdentures (double crown
      technique).
AB  - To evaluate the long term results of telescopically retained overdentures, 92
      patients with a total of 106 overdentures on 236 teeth were examined after two to
      eleven years. Thirty-three teeth were lost during the follow-up period. A higher
      tooth survival rate of the double-crowned teeth was found under mandibular
      overdentures (92%) than under maxillary overdentures (86%) after five years. The
      palladium-silver-alloy used seemed to be more suitable for telescopic crowns than
      the use of precious gold-copper-alloys because of tarnishing the latter alloys.

PMID- 11307389
TI  - The lateral fixation screw in implant dentistry.
AB  - This clinical report presents a means of retaining implant supported
      superstructures using lateral fixation screws (Novadent). 244 lateral fixation
      screws have been used for the retention of a variety of restorations including
      single teeth, short span and full arch bridgework as well as overdenture bars.
      Over a period of observation of 4 years, the authors have found the restorations
      to have effective retention, ease of retrievability, good aesthetics and occlusal
      contours.

PMID- 11307390
TI  - Facial prosthetics: techniques used in the retention of prostheses following
      ablative cancer surgery or trauma and for congenital defects.
AB  - The retention of facial prostheses is a major factor influencing the successful
      outcome of rehabilitative treatment following ablative cancer surgery or trauma
      and for the prosthetic replacement of congenitally absent tissue. Since the
      sixteenth century to the present day, facial prosthetic devices have been
      retained by methods including adhesives and spectacle frames. The introduction of
      the Branemark extra oral implant system enhanced the stability of life-like
      prostheses thus giving patients more confidence in their use. This paper outlines
      the retention systems commonly used at the authors unit and the benefits gained
      by the use of implants to retain facial prostheses. The use of a single stage
      surgical technique instead of the usual two stage procedure is detailed.

PMID- 11307391
TI  - Anterior loop of the mental canal: an anatomical-radiologic study.
AB  - This study sought to characterize the anatomical dimensions of the anterior
      mental loop and to determine the accuracy of conventional radiographs in
      identifying its presence and dimensions. The study group consisted of 46
      hemimandibles fixed in formalin. Radiographs of the area between the mental
      foramen and the midline were obtained and evaluated for each hemimandible,
      followed by dissection and physical examination of the same area. Anatomically,
      an anterior loop of the mental nerve was observed in only 13 hemimandibles (28%).
      The anterior extension of the loop ranged from 0.4 to 2.19 mm. No correlation was
      found between the radiographic image and the anatomical shape of the loop. Of the
      radiographically diagnosed loops, 40% were not seen in anatomical examination. In
      cases with a false radiologic loop, a correlation was found between the diameter
      of the origin of the incisive canal and the radiologic interpretation of the
      loop. The radiologic appearance or diagnosis of the anterior mental loop in
      cadaver mandibles does not disclose the true ramification of the inferior
      alveolar nerve to the mental and incisive nerve.

PMID- 11307392
TI  - Laser Doppler flowmetry for clinical detection of blood flow as a measure of
      vitality in sinus bone grafts.
AB  - Blood flow in sinus grafts and adjacent oral tissues was investigated using Laser
      Doppler Flowmetry (LDF). Special LDF probes were inserted into pilot drill holes
      before the final sizing drill to prepare recipient dental implant sites in the
      grafted sinus after a 6-month maturation time. Patients in the study had
      previously undergone sinus grafting with irradiated mineralized cancellous
      allografts alone, which had been prepared by either hydration in saline or
      autogenous serum. LDF detected positive blood flow in all sites investigated. No
      significant differences were recorded between saline- and serum-treated grafts.
      However, blood flow at the superior aspect of the grafts was significantly lower
      than that recorded at midway and at the most inferior aspects of the sinus
      grafts. Sinus membrane blood flow was noted to be very low compared with bone and
      mucosal sites. LDF may be a useful technique in the verification of vitality in
      sinus grafts relative to that of adjacent oral structures.

PMID- 11307393
TI  - Histomorphometric study of bone healing around laminar implants in experimental
      diabetes.
AB  - The aim of this study was to evaluate the effects of experimental diabetes on the
      healing period leading to osseointegration. Wistar rats were injected with a
      single dose of streptozotocin (STZ); body weight and food intake were assessed
      every 48 hours. On days 2, 12, 26, and 42 post-STZ, glucemia, plasma hemoglobin,
      and urea were determined. Twelve days post-STZ, a titanium laminar implant was
      placed in the right tibia of each rat. Two groups of 20 rats each were killed on
      days 14 and 30 postimplantation, respectively. Results (ANOVA test) showed STZ
      treated rats to have 1) a significant decrease in body weight; 2) an increase in
      food intake; 3) normal hemoglobin and plasma urea values; 4) a significant
      increase in glucemia; and 5) a decrease in tibiae length. Microscopic evaluation
      14 days postimplantation revealed the presence of woven bone, and, at 30 days,
      laminar bone was in contact with the implant. Our findings show that, in this
      model of periimplant bone repair and under the experimental conditions stated
      herein, STZ-induced diabetes retards periimplant bone healing.

PMID- 11307394
TI  - Maintaining cosmetics and marginal bone with a dental implant.
AB  - Inherent concerns for all implant systems exist. These concerns include complex
      restorative procedures, abutment rotational problems, marginal bone loss, and, in
      some cases, less than ideal cosmetic results. To overcome or reduce these
      problems, a new implant has been designed. The implant has been evaluated in this
      prospective study. Thirty-three new design implants were placed in 11 patients
      for an average time of 27.25 months. The new implant design proved to be easier
      to restore, posed no abutment rotational problems, resulted in no marginal bone
      loss problems (positive bone maintenance), and produced exceptional favorable
      cosmetic results.

PMID- 11307395
TI  - Connection designs of three different implant systems in the resorbed edentulous
      maxilla: a case report.
AB  - This report presents the mixed use of three different system implants for an
      implant-supported fixed bridge in a resorbed maxilla. Two of six implants that
      had been placed were lost. New implants were combined with the remaining implants
      that had been placed by the previous dentists in 1992 and 1997. The three implant
      systems consisted of the following: one incorporated an intramobile element into
      an implant device, and the other two were whole titanium screw-type implants (one
      with a machined surface and the other with a plasma-sprayed surface). This
      clinical report describes the connection designs of these different system
      implants to the fixed bridge and lists the complications that followed.

PMID- 11307396
TI  - Postextraction ridge preservation using a synthetic alloplast.
AB  - Ridge preservation is the prevention of the 40% to 60% jaw-bone atrophy that
      normally takes place 2 to 3 years postextraction and continues at a rate of 0.25%
      to 0.5% per year until death. It is achieved by the immediate grafting of the
      extraction socket with or without the use of an immediate implant. It offers the
      dentist the ability to preserve the alveolar ridge for future implant and
      restorative dentistry, to achieve anterior esthetics, and to prevent
      postoperative pain and bleeding. The practice of ridge preservation involves
      advanced extraction therapy and replacement therapy.

PMID- 11307397
TI  - Osteotome sinus elevation and implant placement with narrow size bioactive glass.
AB  - A procedure using osteotomes and bioactive glass as an alloplastic bone graft
      material is discussed, and three clinical cases are reviewed. Bioactive glass of
      a narrow size range (300-355 microns) has been shown to be osteoconductive and
      allows for good integration and regeneration of surrounding bony tissue. We have
      found this technique to be a predictable method of preparing and placing longer
      implants in the region of the maxillary premolar region without the need for
      additional donor site morbidity.

PMID- 11307398
TI  - Fabrication of a single-appointment emergency overdenture using failed fixed
      prosthetics: a case report.
AB  - A single appointment fabrication of an emergency overdenture is described. The
      technique was used in the treatment of a failed implant-supported fixed bridge
      that was unable to be reinserted due to fractured components and a lack of
      passive fit. This technique may also be used for the treatment of a failing
      natural dentition as well as an implant prosthesis.

PMID- 11307399
TI  - Case report: restorative maintenance of prostheses stabilised by non-endosseous
      implants.
AB  - For over a century, dentists have looked to dental implants to enhance the
      stability of dental prostheses. During this time, many approaches and different
      materials have been used. The purpose of this article is to report on two cases
      where non-endosseous implant systems were used and to outline how the replacement
      prostheses were customiZed to comply with the different implant types.
      Intramucosal inserts and sub-periosteal implants are briefly reviewed in the
      context of current prosthodontic practise. There are still a small number of
      patients with clinically acceptable intramucosal and subperiosteal implant
      retained prostheses, which will continue to need servicing and replacement.

PMID- 11307400
TI  - Tooth colour analysis by a new optoelectronic system.
AB  - The difficulties in assessing and comparing tooth shades are well documented.
      This pilot study introduces an alternative method of photoelectric tooth colour
      measurement, the silicon photodiode array apparatus. This apparatus was used to
      determine colorimetric values for samples of acrylic resin teeth and the results
      compared with colour values obtained using a conventional photoelectric
      tristimulus colorimeter. Whilst a significant difference was found between some
      colorimetric data produced by the two types of apparatus for the same sample
      these differences existed purely at the mathematical level and would not be
      perceived by a human observer.

PMID- 11307401
TI  - The effectiveness of palate-less versus complete palatal coverage dentures (a
      pilot study).
AB  - The aim of this pilot study was to evaluate the effectiveness of palate-less
      dentures as a substitute for conventional complete palatal coverage. Ten
      edentulous patients who had recently received maxillary and mandibular complete
      dentures were included in the study. The patients' maxillary conventional
      dentures were duplicated to construct 'U' shape palate-less dentures. A strain
      gauge biting fork was used to compare the maximum biting force and chewing tests
      using almond were performed. They failed to show significant differences. Eight
      patients were more comfortable with the palate-less dentures than the complete
      palatal coverage. It was concluded that Palate-less dentures could be as
      effective as dentures with complete palatal coverage.

PMID- 11307402
TI  - Case report: a non-rigid connector for a resin bonded bridge.
AB  - The use of rigid connectors between pontics and retainers is common for
      conventional bridges. Restoration of two missing teeth and an intermediate pier
      abutment with a rigid bridge is not an ideal treatment. In this report a resin
      bonded bridge with a non-rigid connector within the pontic distal to the pier
      abutment was constructed and remained in place without debonding for seven years.

PMID- 11307403
TI  - Disinfection of dental impressions and occlusal records by ultraviolet radiation.
AB  - As chemical disinfection of dental impressions may cause adverse effects on
      materials and the dental personnel this study examined disinfection by
      ultraviolet radiation. Alginate, addition silicone rubber and red wax
      contaminated by Streptococcus salivarius, Fusobacterium nucleatum and five other
      bacteria in different suspension media were radiated for up to 18 min, and the
      number of colony forming units was compared to non-radiated controls. The effect
      of ultraviolet radiation differed among bacterial species and depended on the
      organic content in the suspension. Generally, the bacterial reduction after
      ultraviolet radiation was below 4 log steps and thus insufficient for
      disinfection of dental impressions.

PMID- 11307404
TI  - A dental laboratory study of the dimensions of metal frameworks for fixed partial
      dentures.
AB  - The purpose of this study was to record the dimensions of the metal substructure
      of metal ceramic restorations under fabrication in dental laboratories. The
      dimensions of the joints as well as the metal thickness of the occlusal, buccal
      and lingual/palatal surfaces of the abutment crowns were measured on 115 fixed
      partial dentures. The results showed that the greatest dimensions in a vertical
      direction were found in the anterior region, and in a horizontal direction in the
      posterior region. The occlusal, buccal and lingual/palatal surfaces of the
      abutment crowns often showed sub-optimal dimensions.

PMID- 11307405
TI  - Where's the rush?

PMID- 11307406
TI  - Sinus graft procedures and implant dentistry: a review of 21 years of surgical
      experience (1979-2000).

PMID- 11307407
TI  - Stress distribution in the single-unit osseointegrated dental implant: finite
      element analyses of axial and off-axial loading.
AB  - Occlusal overload may contribute to the extensive crestal bone loss often noted
      around late-failure dental implants. A particularly high risk of traumatic
      overload occurs with the posterior single-unit implant restoration because the
      restoration itself is usually wider than the implant, creating the potential for
      a cantilever effect with high bending moments. The objective of this study was to
      evaluate the simulated effects of axial and off-axial vertical loads on stress
      gradients at the implant/bone interface of a single-unit osseointegrated root
      form endosseous dental implant. A two-dimensional finite element model was
      generated. A 490-N load was applied at 0, 2, 4, and 6 mm from the vertical axis
      of the implant. Off-axis loading resulted in greatly increased compressive
      stresses within the crestal cortical bone on the side to which the load was
      applied and similarly increased tensile stresses on the side opposite the load.
      These stresses increased considerably with each mm increase off axis of the
      applied load. These data suggest that off-axis loading of single-unit implant
      restorations provides a significant contribution to increased stresses at the
      implant/cortical bone interface. The distance off axis at which the load is
      applied is also significant.

PMID- 11307408
TI  - Evaluation of guided bone regeneration in rabbit femur using collagen membranes.
AB  - The aim of the study was to evaluate the mechanical performance and the structure
      of neoformed bone around hydroxyapatite-coated titanium fixtures according to
      guided bone regeneration techniques. Ten hydroxyapatite-coated titanium fixtures
      were inserted in the femurs of five rabbits, in which a cortical defect was
      created and after the insertion of the fixture, covered with a resorbable
      membrane obtained from bovine Achilles tendon collagen Type I (A implant). In the
      same femur, a second fixture was inserted in similar cavities without application
      of the membrane (B implant). After 60 days, the animals were sacrificed, and
      block sections of the femoral bone containing the implants were embedded in
      polymethylmetacrylate and subjected to tensile shear-stress at break testing.
      After the detachment of the implants from the bone, their surfaces were examined
      with a scanning electron microscope. Tensile shear-stress values for A and B
      implant specimens were comparable to some extent, but the former had a lower
      performance. In this regard, scanning electron microscope observations showed
      that the neoformed cortical bone present cervically around implant A was much
      thicker than around implant B.

PMID- 11307409
TI  - Evaluation of the effects of different biomaterials on bone defects.
AB  - Studies concerning natural and synthetic graft materials that have been used in
      different medical procedures have focused on freeze-dried bone, coral,
      hydroxylapatite, and tricalcium phosphate. This study histologically investigates
      the effects of these materials on the healing of bone defects. The experiments
      were performed on 30 albino rabbits. Cavities were drilled in the posterior right
      tibias of rabbits and were filled with coral, freeze-dried bone, hydroxylapatite,
      or calcium hydroxide. One cavity was left unfilled as a control. The bone in
      which the materials were implanted was excised at 7, 15, 30, 45, and 60 days.
      After the histological staining procedures, the prepared materials were observed
      using a light microscope. Although all materials showed good bone remodeling at
      the end of 60 days, coral and hydroxylapatite materials could be seen in the bone
      structure. The most effective materials within bone defect improvement were
      freeze-dried bone and calcium hydroxide.

PMID- 11307410
TI  - Reuse of healing abutments: an in vitro model of plasma cleaning and common
      sterilization techniques.
AB  - The reuse of transgingival healing abutments has been advocated by several
      implant manufacturers, but cleaning and sterilization procedures to yield clean
      and optimal surfaces have yet to be developed. The objective of this in vitro
      project was to investigate various cleaning and sterilization regimens for the
      removal of biological debris to support reattachment of subgingival connective
      tissue. Simulated clinical healing abutment surfaces were exposed to culture
      medium with serum for 1 hour to simulate biological exposure. Simulated healing
      abutment surfaces not contaminated by serum were used to represent the "as-is"
      healing abutment surface without prior in vivo use. The discs were cleaned with
      detergent before sterilization by ultraviolet light (UV) or steam autoclaving
      (AC) both with and without 1- and 5-minute plasma cleaning (PC). A series of
      surface analytical techniques (XPS, AES, and surface contact angles) and in vitro
      analysis of cell attachment and spreading using gingival fibroblasts were
      performed. After exposure to the simulated biological conditions, clinical
      cleaning followed by UV resulted in contaminated surfaces and relatively high
      levels of cell attachment. PC before UV treatment enhanced surface energetics but
      did not affect cell attachment and spreading. AC increased surface wetting
      angles; which were decreased somewhat by previous PC. Cell attachment was
      significantly reduced by AC. Although some increase in cell attachment after
      longer plasma cleaning was noted in the AC group, no difference in cell spreading
      was seen in any AC group. Cell spreading seemed to be less for all AC groups
      compared with all UV, as-is, and control groups. Although certain cleaning (PC)
      and sterilization (UV) procedures can be effective for cleaning transgingival
      healing abutments, those using AC are questionable due to their propensity for
      organic and inorganic contamination and unfavorable surface alteration.

PMID- 11307411
TI  - Conventional versus laser-assisted therapy of periimplantitis: a five-year
      comparative study.
AB  - Between 1994 and 1999, 50 patients were treated with either profound
      parodontopathy (30) or periimplantitis (20). Half of each of the two groups of
      patients was treated conventionally, and the other half was treated with laser
      support. Before the operation, microbiological examinations were carried out, in
      addition to registering the clinical findings and taking x-rays. These procedures
      were repeated after the operation, and again after 6, 12, 24, 36, 48, and 60
      months. The surgical part of therapy for each half of the patient groups included
      surface decontamination with diode laser light (1-watt output, maximum of 20
      seconds) in addition to conventional procedures. The values of the laser
      supported therapy were lower than those specified in the relevant literature. The
      relapse rate of the two diseases (13% for the periimplantitis and 23% for the
      parodontopathy group) after 5 years was lower than the comparative values of
      researched literature where decontamination was not included in the therapy. We
      think that integrating diode laser light decontamination in the approved
      treatment schemes for periimplantitis and parodontitis contributes considerably
      to the success of this therapy.

PMID- 11307413
TI  - Morphological study of Osteoplate 2000-extension implants after bending.
AB  - Unfavorable anatomical conditions of implant sites often require the insertion of
      implants in a direction that may interfere with the positioning of
      suprastructural elements in a functionally and esthetically satisfying manner. In
      some implant systems, bending of the implant neck is one of the possible methods
      for optimizing the insertion angle for the superimposed prosthesis. The aim of
      this study was to investigate whether bending procedures of the implant neck
      cause changes in the surface properties at the implant neck area. After bending
      of the implant neck up to 30 degrees, scanning electron microscopy revealed
      changes in the surface texture of the titanium. Superficial rips approximately 5
      microns wide and 100 microns long had formed. These findings were confirmed by
      metallographic examinations. Values of Vickers hardness testing in the implant
      neck area after bending of 30 degrees showed significant differences between the
      compression or stretched zone and the neutral zone of the bending area. Bending
      of the implant neck between 0 and 20 degrees may influence the surface
      morphology, promoting superficial rips. Plaque accumulation and mechanically
      induced mucosal irritations due to changes of surface morphology and properties
      by bending should be further analyzed.

PMID- 11307412
TI  - Preliminary evaluation of a new dental implant design in canine models.
AB  - Problems with crestal bone resorption and bone adaptation to dental implants in
      compromised and weak bone present clinical challenges due to insufficient bone
      volume. Mathematical models have shown that a new, square-thread, dental implant
      design increases functional surface area and reduces shear loading at the implant
      interface. The aim of this investigation was to evaluate the ability of bone to
      grow between the threads of the new implant and its general biocompatibility in a
      canine model. Test implants were placed in the mandibles of four beagle dogs
      after posterior partial edentulism. Three months after implantation, the animals
      received independent fixed partial dentures, were followed for an additional 6
      months, and then euthanized for histological analyses. Analyses revealed that
      bone grew between the threads and closely apposed the new implant design.
      Histological observations also revealed that the inferior aspect of the test
      implant threads were apposed by more bone than the coronal aspect, suggesting a
      biological advantage for the compressive load transfer mechanism of the new
      implant design. The results of this study revealed that the new implant design
      became osseointegrated with bone growing between the threads of the device.

PMID- 11307414
TI  - Reconstruction of severely resorbed atrophic maxillae and management with
      transitional implants.
AB  - The reconstruction of the severely resorbed maxilla requires complex surgical
      treatment sequencing. Often, multiple grafting procedures are required either
      before or in conjunction with implant placement. Regardless of the surgical
      modality, the grafting procedures and the placement of implants in poor quality
      bone require undisturbed healing during which no pressure is placed on the
      grafted implant ridge. The use of transitional implants allows the surgeon to
      provide stable temporary prostheses throughout the healing phase, while
      preventing pressure from being placed on the grafted or implant reconstructed
      ridge throughout the maturation. These transitional implant-supported temporaries
      allow the implant team to maintain vertical dimension, and they provide the
      patient with the benefits of implant-supported restorations during the time
      leading up to final prosthetic reconstruction.

PMID- 11307415
TI  - Implant-related damage to an adjacent tooth: a case report.
AB  - Implant-related damage to an adjacent tooth is shown to be an iatrogenic
      complication. The affected tooth may require apical curettage, root canal
      therapy, apicoectomy, or even extraction. A case is presented of a patient who
      complained of damage to an adjacent root after implant placement.

PMID- 11307417
TI  - Alarms are sounded, are we listening?

PMID- 11307416
TI  - Treatment options for augmentation of the posterior maxilla.
AB  - The uses of conventional sinus augmentation procedures, trephines and osteotomes,
      with and without concomitant buccal-lingual ridge augmentation are discussed.
      Indications and contraindications for the application of each therapeutic
      modality, material selection, and the appropriate timing of implant placement are
      detailed.

PMID- 11307418
TI  - Fixed functional appliances--a classification.

PMID- 11307419
TI  - Craniometer/Aqualizer techniques.

PMID- 11307420
TI  - Visiting another planet.

PMID- 11307421
TI  - The use of a face mask for postoperative retention in cleft lip and palate
      patients.
AB  - Surgical relapse in cleft lip and palate patients following Le Fort I osteotomy
      can be pronounced due to the presence of scar tissue from previous surgical
      episodes. This article reviews the literature on the use of protraction face
      masks. It describes the use of a face mask in the postoperative management of
      osteotomy patients undergoing surgery for the correction of severe skeletal Class
      III relationships. The management of a patient with repaired unilateral cleft lip
      and palate is illustrated.

PMID- 11307422
TI  - Cephalometric characteristics of Korean Class III surgical patients and their
      relationship to plans for surgical treatment.
AB  - In comparison to gender-matched normal Koreans, Korean patients selected for
      surgical correction of skeletal Class III problems have, on average, a shorter
      anterior and posterior cranial base, a shorter maxilla, a longer mandible,
      increased lower facial height, and a retrusive upper lip. In both males and
      females, about 40% of a group of Class III patients scheduled for surgery had a
      maxilla within one standard deviation of the normal position and a prognathic
      mandible, as compared with a group of normal Korean adults. Almost as many males
      (37%) in the surgical group had both a retrognathic maxilla and a prognathic
      mandible, while 18% had a retrognathic maxilla and normal mandible. In females,
      25% had only a retrognathic maxilla and 25% had both jaws outside the normal
      range. The percentage of the Korean patients whose Class III relationship was
      primarily a result of mandibular prognathism (48%) is more than twice as high as
      the corresponding number for American Class III surgical patients (19%), somewhat
      higher than in Chinese patients (39%), and similar to the percentage of Japanese
      (50%). Maxillary surgery, alone or in conjunction with mandibular setback, is
      currently used in the treatment of most Class III patients. Both the esthetic
      consideration of widening the already broad Asian nose and the relative
      proportions of maxillary versus mandibular abnormalities suggest that mandibular
      setback alone can be considered for a higher number of Asian than Caucasian Class
      III patients.

PMID- 11307423
TI  - An implant to eliminate anchorage loss during molar distalization: a case report
      involving the Graz implant-supported pendulum.
AB  - Based on the philosophy of the pendulum appliance, a new non-integrated implant
      supported device is presented, the Graz Implant-Supported Pendulum (GISP). It is
      designed to distalize maxillary first and second molars in adults. It consists of
      2 parts: the anchorage plate, which is fixed to the palatal bone via 4
      miniscrews, and the removable part, which is a pendulum-type appliance. A
      finished clinical case is shown, and experiences with the GISP in comparison with
      other orthodontic implants are discussed. The system can be loaded 2 weeks after
      surgical placement, actively distalize maxillary molars consecutively, serve as
      an active anchor unit, and provide stability against rotational movements.

PMID- 11307424
TI  - Obstructive sleep apnea (OSA): a cephalometric analysis of severe and non-severe
      OSA patients. Part I: Multiple comparison of cephalometric variables.
AB  - One hundred male obstructive sleep apnea (OSA) patients were classified into 2
      groups, on the basis of Apnea-Hypopnea Index (AHI), as severe (AHI > or = 50) and
      non-severe (AHI < 50). A comprehensive cephalometric analysis of
      cervicocraniofacial skeletal morphology and upper airway soft tissue morphology
      was performed in 51 non-severe OSA patients, 49 severe OSA patients, and 36
      controls with the purpose of examining the different features among these 3
      groups. Sixty-eight cephalometric variables were compared among these 3 groups by
      1-way analysis of variance with post hoc Bonferroni test. The results showed that
      both OSA groups had aberrations of cervicocraniofacial skeletal morphology and
      upper airway soft tissue morphology versus the controls. Severe OSA patients
      demonstrated increased maxillo-mandibular retrognathism, with a high mandibular
      plane angle resulting from increased anterior lower facial height and decreased
      posterior lower facial height, versus the non-severe OSA group. The
      craniocervical extension, forward head posture, inferiorly positioned hyoid bone,
      and the enlarged and elongated soft palate and upright tongue posture were more
      exaggerated as well. These findings imply that there should be different
      treatment regimens for the 2 subgroups of OSA patients to achieve treatment
      success. Cephalometric analysis is therefore highly recommended to verify the
      aberrant cervicocraniofacial morphology in severe and non-severe OSA patients.

PMID- 11307426
TI  - Clinical research, protection of human subjects, and regulation.

PMID- 11307425
TI  - Lingual orthodontics and orthognathic surgery.
AB  - Lingual orthodontics is an appealing option for patients requiring orthognathic
      surgical correction, since these patients are invariably adults or mature
      teenagers who are no longer at the usual "orthodontic age." Appearance is
      undoubtedly the most important motivating factor for adults seeking orthodontic
      treatment, and since the more physically attractive person has the advantage over
      the not-so-attractive person, it is self-evident that these patients would prefer
      an appliance that is less visible. Using the Ormco, Creekmore, or Begg lingual
      appliances in the maxillary arch and a labial appliance in the mandibular arch,
      the authors have successfully treated a variety of dentofacial deformities with a
      combined lingual orthodontic and surgical approach. The aim of this article is to
      establish some guidelines for the treatment of a variety of surgical cases and to
      highlight what are perceived to be the advantages and disadvantages of these 3
      lingual appliances in the treatment of orthognathic cases and of the lingual
      orthognathic approach in general.

PMID- 11307427
TI  - Long-term stability of mandibular setback surgery: a follow-up of 80 bilateral
      sagittal split osteotomy patients.
AB  - The objective of this cephalometric study was to evaluate skeletal stability and
      time course of postoperative changes in 80 consecutive mandibular prognathism
      patients operated with bilateral sagittal split osteotomy (BSSO) and rigid
      fixation. Lateral cephalograms were taken on 6 occasions: immediately
      preoperative, immediately postoperative, 2 and 6 months postoperative, and 1 and
      3 years postoperative. The results indicate that BSSO with rigid fixation for
      mandibular setback is a fairly stable clinical procedure. Three years after
      surgery, mean relapse at pogonion represented 26% of the surgical setback (19% at
      point B). Most of the relapse (72%) took place during the first 6 months after
      surgery. Clockwise rotation of the ascending ramus at surgery with lengthening of
      the elevator muscles, though evident in this study and apparently responsible for
      the early horizontal postoperative changes, does not seem to be associated with
      marked relapse. Changes occurring in some of the younger patients between 1 and 3
      years postoperatively are likely to be manifestations of late mandibular growth.

PMID- 11307428
TI  - Stability of extraoral vertical ramus osteotomy: plate fixation versus
      maxillomandibular/skeletal suspension wire fixation.
AB  - The objective of this cephalometric study was to evaluate skeletal stability and
      time course of postoperative changes in 2 groups of mandibular prognathism
      patients following extraoral oblique vertical ramus osteotomy (VRO). One group (n
      = 22) received maxillomandibular fixation and skeletal suspension wires (MMF
      group) for a period of 8 weeks. In the other group (n = 22), the segments were
      rigidly fixed with plates and the patients were allowed to function immediately
      after surgery. Lateral cephalograms were taken on 5 occasions: immediately
      presurgical, immediately postsurgical, 8 weeks postsurgical, 6 months
      postsurgical, and 1 year postsurgical. During the first 8 weeks after surgery,
      the MMF group demonstrated posterior movement of the mandible, with an increase
      in mandibular plane angle, shortening of the rami, and dental compensations. Upon
      release of MMF and skeletal suspension wiring, a small anterior relapse tendency
      was observed, but the net setback 1 year after surgery was still greater than the
      actual surgical setback. In the plate fixation group, postoperative changes were
      mainly in the form of a small anterior relapse tendency in the range of 10% of
      the surgical setback. The results indicate that the use of plate fixation with
      VRO, while eliminating the inconvenience for the patient of several weeks of MMF
      and preventing the early side effects observed in the MMF group, also resulted in
      a more predictable surgical procedure, with excellent stability 1 year after
      surgery.

PMID- 11307429
TI  - Comparative SEM study on the effect of root conditioning with EDTA or
      tetracycline Hcl on periodontally involved root surfaces.
AB  - This study compared the surface characteristics of periodontally diseased single
      human teeth extracted after treatment with either EDTA or Tetracycline Hcl. The
      study was comprised of 30 teeth from 20 patients with advanced periodontal
      disease. Diseased root surfaces were root planed by hand curette or finishing
      bur. The teeth were sectioned and solutions of EDTA (pH 7.3) or Tetracycline Hcl
      (pH 1.8) were applied to the surface with cotton pellets for 3 minutes using
      light pressure. Specimens were processed and examined by Scanning Electron
      Microscope. The surfaces of both etched treated sets of specimens differed
      considerably from specimens treated with root planing alone, regardless of the
      root planing method. The etched specimens exhibited numerous dentinal tubules
      exposed by the removal of smear layer.

PMID- 11307430
TI  - Juxtacortical osteogenic sarcoma of mandible. A case report.
AB  - Juxtacortical osteogenic sarcoma of bone is a relatively uncommon form of
      osteogenic sarcoma. In the jaw bones, it is extremely rare. Here, we present a
      case of Juxtacortical Osteogenic Sarcoma of mandible in a 45 year old man which
      presented as an epulis in the mandibular incisor region.

PMID- 11307431
TI  - Eagle' syndrome. Anatomy of the styloid process.
AB  - The observations made on the angulations and the length of styloid processes from
      a hundred skulls are presented. Morphometrical data compiled is correlated to
      those available in literature. The dimension and angularity of the process when
      in extreme is known to produce symptoms classified as Eagle's syndrome. This
      paper discusses the probable incidence of dysphagia due to predisposition of the
      elongated styloid process in Indian context. Most statistics on the metrics of
      the process are called from radiographic studies done in western centres.
      Osteometry of the styloid with reference to the risk factors in causation of the
      syndromes probably, presented in this paper for the first time in this part of
      the world. It is hoped that despite the rarity of the syndrome, this brief study
      will spur research into the osteological basis for the peculiar clinical
      condition.

PMID- 11307432
TI  - Teeth and numerology from zodiac signs. A correlative study.
AB  - Comparative anatomical descriptions have been time and again mentioned in the
      literature. Based on these aspects, an attempt is made to correlate the
      morphological features of the human teeth, the zodiac sun signs and numerology.
      This unique study (first ever of its kind) is also done with a purpose as to
      whether a particular 'Zodiac Sunsign' or numerology can predict about an
      individual dental health, the same way the future predictions are being made. It
      was quite interesting to note that there are few definite attributable dental
      morphological traits and health to the specific sun signs and numerology.

PMID- 11307433
TI  - Lasers in endodontics: a review.
AB  - Since the development of the ruby laser by Maiman in 1960 and the application of
      the laser for endodontics by Weichman in 1971, a variety of papers on potential
      applications for lasers in endodontics have been published. The purpose of this
      paper is to summarize laser applications in endodontics, including their use in
      pulp diagnosis, dentinal hypersensitivity, pulp capping and pulpotomy,
      sterilization of root canals, root canal shaping and obturation and apicectomy.
      The effects of laser on root canal walls and periodontal tissues are also
      reviewed. The essential question is whether a laser can provide equal or improved
      treatment over conventional care. Secondary issues include treatment duration and
      cost/benefit ratio. This article reviews the role of lasers in endodontics since
      the early 1970s, summarizes many research reports from the last decade, and
      surmises what the future may hold for lasers in endodontics. With the potential
      availability of many new laser wavelengths and modes, much interest is developing
      in this promising field.

PMID- 11307434
TI  - Complications during root canal irrigation--literature review and case reports.
AB  - LITERATURE REVIEW AND CASE REPORTS: The literature concerning the aetiology,
      symptomatology and therapy of complications during root canal irrigation is
      reviewed. Three cases of inadvertent injection of sodium hypochlorite and
      hydrogen peroxide beyond the root apex are presented. Clinical symptoms are
      discussed, as well as preventive and therapeutic considerations.

PMID- 11307435
TI  - Detection of bacterial virulence genes associated with infective endocarditis in
      infected root canals.
AB  - AIM: The aim of this study was to examine whether bacteria associated with root
      canals possess genes that might predispose to bacterial colonization of the
      endocardium. METHODOLOGY: Oligonucleotides were designed from DNA sequences
      encoding the functional binding regions of streptococcal fibronectin-binding
      protein (FnBP) and staphylococcal fibrinogen-binding protein (FgBP). The
      specificity and cross-reactivity of the oligonucleotide primers were
      investigated; streptococcal primers were tested for recognition of FnBP genes in
      other strains of streptococci, and the staphylococcal primers for detection of
      FgBP from other staphylococci. Interspecies specificity of these primers was also
      investigated. In a pilot clinical study, the pulp chambers of 16 nonvital teeth
      without sinus tracts, were opened aseptically. Root canal samples were collected,
      along with samples from the gingival sulcus and anterior nares. From these
      samples DNA was extracted, subjected to polymerase chain reaction (PCR) and
      analysed by agarose gel electrophoresis. RESULTS: Using the streptococcal FnBP
      primers, PCR bands were amplified from eight root canal samples, eight gingival
      samples and three nasal samples. With the staphylococcal primers, PCR bands were
      amplified from seven root canals, 11 gingival and nine nasal samples. This study
      showed that PCR could be used to detect bacteria in root canals that possess
      genes with homology to functional regions of those encoding FnBP or FgBP.
      CONCLUSIONS: If bacteria in root canals possess FnBP or FgBP, they may have the
      potential to cause infective endocarditis.

PMID- 11307436
TI  - Cyclic fatigue of ProFile rotary instruments after clinical use.
AB  - AIM: The purpose of this study was to evaluate cyclic fatigue of .06 ProFile Ni
      Ti rotary instruments after clinical use in molar teeth. METHODOLOGY: In group 1,
      instruments size 40-15 were used in a crown-down technique using 2.5% NaOCl as an
      irrigant. Fifty-two molars were included and 13 sets of Profile Ni-Ti rotary
      instruments were used. Each set of instruments was used in four molars, and was
      steam autoclaved before each use. Group 2 (10 sets of new ProFile Ni-Ti rotary
      instruments) was the control group. Cyclic fatigue was tested by rotating the
      instruments in a 90 degrees metallic tube until they broke. RESULTS: One-way
      analysis of variance did not show any statistically significant differences
      amongst the files from both groups regarding cyclic fatigue. CONCLUSIONS: It was
      concluded that sterilization and clinical use in the presence of NaOCl did not
      lead to a decrease in the number of rotations to breakage of the files.

PMID- 11307437
TI  - Endodontic retreatment decisions: no consensus.
AB  - AIM: The objectives of the present study were to: (i) evaluate the consensus, if
      any, amongst dental schools, students and their instructors managing the same
      clinical cases, all of which involved endodontically treated teeth; and (ii)
      determine the predominant proposed treatment option. METHODOLOGY: Final year
      students, endodontic staff members and instructors of 10 European dental schools
      were surveyed as decision makers. Fourteen different radiographic cases of root
      canal treated teeth accompanied by a short clinical history were presented to
      them in a uniform format. For each case the decision makers were requested to:
      (i) choose only one out of nine treatment alternatives proposed, from 'no
      treatment' to 'extraction' via 'retreatment' and 'surgery' (ii) assess on two 5
      point scales: the difficulty of making a decision, and the technical complexity
      of the retreatment procedure. RESULTS: The results indicate wide inter- and also
      intra-school disagreements in the clinical management of root canal treated
      teeth. Analysis of variance showed that the main source of variation was the
      'school effect', explaining 1.8% (NS) to 18.6% (P < 0.0001) of the treatment
      variations. No other factor explained as much variance. Decision difficulty was
      moderately correlated to technical complexity (Pearsons' r ranging from 0.19 to
      0.35, P < 0.0001). CONCLUSIONS: No clear consensus occurred amongst and within
      dental schools concerning the clinical management of the 14 cases. The lack of
      consensus amongst schools seems to be due mainly to chance or uncertainty, but
      can be partly explained by the 'school effect'.

PMID- 11307438
TI  - Influence of calcium hydroxide intracanal dressings on the prognosis of teeth
      with endodontically induced periapical lesions.
AB  - AIM: This prospective clinical study explored the influence of calcium hydroxide
      as an interappointment dressing on the healing of periapical lesions associated
      with pulpless teeth that had not been endodontically treated previously. This was
      achieved by comparing the prognosis after a two-visit root canal treatment with
      that following a one-visit treatment. METHODOLOGY: Seventy-three patients were
      recruited having one tooth with an endodontically induced lesion. Of these
      patients, 67 could be re-examined. Calcium hydroxide was placed in the
      instrumented root canals of 31 teeth for at least one week and the treatment
      finished at the second visit. Thirty-six teeth were root canal treated at one
      visit. The criteria for success were the absence of signs and symptoms indicating
      an acute phase of periapical periodontitis and radiographically a periodontal
      ligament space of normal width. Methods for event time analysis were used to
      evaluate and compare the prognosis of both treatment approaches. RESULTS: The
      probability that complete periapical healing will take place increased
      continuously with the length of the observation period. In both treatment groups
      the likelihood that the root canal treatment yields a success within an
      observation time of five years exceeded 90%. A statistically significant
      difference between the two treatment groups could not be detected. CONCLUSIONS:
      From a microbiological perspective, one-visit root canal treatment created
      favourable environmental conditions for periapical repair similar to the two
      visit therapy when calcium hydroxide was used as antimicrobial dressing. One
      visit root canal treatment is an acceptable alternative to two-visit treatment
      for pulpless teeth associated with an endodontically induced lesion.

PMID- 11307439
TI  - The effects of Ledermix paste on discolouration of mature teeth.
AB  - AIM: The aims of this study were to: (i) investigate the effects of Ledermix
      paste as an intracanal medicament on discolouration of mature teeth, (ii) examine
      whether the discolouring effects were related to the method of application, and
      (iii) examine the effects of sunlight upon discolouration of mature teeth.
      METHODOLOGY: The root canals of 45 mature extracted human teeth were prepared and
      filled with either Ledermix paste, calcium hydroxide [Ca(OH)2], or saline. In
      group 1, Ledermix paste was placed apical to the cemento-enamel junction (CEJ),
      whilst in groups 2 and 3 the paste filled the entire pulp chamber and root
      canals. In group 4, a Ca(OH)2 and methyl cellulose paste and, in group 5, saline
      (control) were allowed to fill the pulp chamber and the root canals. Group 3
      teeth were kept in the dark and the other groups were exposed to indirect
      sunlight for 12 weeks. RESULTS: After 12 weeks, sunlight exposure had caused dark
      grey-brown staining of the teeth in the Ledermix groups, but this did not occur
      when the teeth were kept in the dark. More severe staining was noted when
      Ledermix paste filled the pulp chamber than when the paste was restricted to
      below the CEJ. CONCLUSIONS: It was concluded that Ledermix paste may cause
      discolouration of teeth. Such effects can be minimized if placement of the paste
      is restricted to below the gingival margin. Clinicians should ensure that
      Ledermix paste is not left on the walls of access cavities.

PMID- 11307440
TI  - The effects of Ledermix paste on discolouration of immature teeth.
AB  - AIM: The aims of this study were to: (i) investigate the effects of Ledermix
      paste as an intracanal medicament on discolouration of immature teeth, (ii)
      examine whether the discolouring effects were related to the method of
      application, (iii) examine the effects of sunlight upon discolouration of
      immature teeth and (iv) compare the degree of discolouration between mature and
      immature teeth. METHODOLOGY: The root canals of 45 immature extracted human teeth
      were prepared and filled with either Ledermix paste, calcium hydroxide [Ca(OH)2],
      or saline. In group 1, Ledermix paste was only placed apical to the cemento
      enamel junction (CEJ) whilst in groups 2 and 3, the paste filled the entire pulp
      chamber and the root canals. In group 4, Ca(OH)2 paste and in group 5, saline
      (control) were allowed to fill the pulp chamber and the root canals. Group 3
      teeth were kept in the dark and the other groups were exposed to daylight for 12
      weeks. RESULTS: After 12 weeks, sunlight exposure had caused dark grey-brown
      staining in the Ledermix groups but this did not occur when the teeth were kept
      in the dark. More severe staining was noted when Ledermix paste filled the pulp
      chamber than when the paste was restricted to below the CEJ and when teeth were
      exposed to sunlight. When compared to the results of a similar study using mature
      teeth, the results were similar but the immature teeth were more severely stained
      than the mature teeth. The Ca(OH)2 paste caused an increase in lightness and
      yellowness in immature teeth. CONCLUSION: It was concluded that Ledermix paste
      may cause discolouration of immature teeth. Such effects can be minimized if
      placement of the paste is restricted to below the gingival margin. Clinicians
      should ensure that Ledermix paste is not left on the walls of access cavities,
      especially in immature teeth.

PMID- 11307441
TI  - A laboratory study evaluating the release of hydroxyl ions from various calcium
      hydroxide products in narrow root canal-like tubes.
AB  - AIM: The aim of the present study was to describe pH changes in a variety of
      buffering solutions within a narrow test tube containing either a gutta-percha
      point with incorporate calcium hydroxide, a commercial calcium hydroxide paste
      (Calcicur) or a freshly mixed paste of calcium hydroxide in distilled water.
      METHODOLOGY: The test material was placed centrally in a test tube of 2 mm inner
      diameter. Saline (1%) was placed at one end, whilst the buffering solutions were
      introduced at the other. The pH of the buffering solutions was monitored using
      electrodes placed at each end of the test tube. RESULTS: It was found that the pH
      4.01 buffer strongly resisted pH changes at levels below 6.0, whilst saliva and
      bovine serum was buffered less and more evenly in the whole range up to pH 11.5.
      The calcium hydroxide containing gutta-percha points caused the pH to increase
      quickly in the sodium chloride solution to levels above 11.5. However, in bovine
      serum, in saliva and in the pH 4.01 buffer the pH remained below 8.5, 8.0 and
      6.0, respectively, 1 mm from the point. In contrast, the release of hydroxyl ions
      from the two calcium hydroxide pastes brought pH above pH 11.5 irrespective of
      the buffering of the solutions 5 mm from the paste. CONCLUSION: It is concluded
      that Calcicur and the calcium hydroxide-water mixture contained substantially
      more available calcium hydroxide than did the calcium hydroxide containing gutta
      percha points, with the result that the release of hydroxyl ions from the points
      was limited in comparison to that from the pastes.

PMID- 11307442
TI  - The use of 3D computerized reconstruction for the study of coronal microleakage.
AB  - AIM: The purpose of this study was to evaluate a new method for studying coronal
      microleakage associated with root-filled teeth. METHODOLOGY: Twenty human
      mandibular posterior teeth were prepared chemomechanically with the stepback
      technique and then divided into two groups of 10 teeth each. The canals were
      filled using lateral condensation of gutta-percha points; Roth's 801 was used as
      a sealer for the first group, and Ketac-Endo for the second. After 48 h, the
      temporary fillings in the access cavities were removed, the roots coated with
      three layers of nail polish and then the teeth were exposed to artificial saliva
      for 40 days. Subsequently, the crowns of the teeth were placed into Indian ink
      for 4 days before the coating was removed and the teeth embedded in a two-phase
      polyester resin. Serial cross sections were taken from each specimen using a
      microtome, and each cross section photographed under a stereoscopic microscope.
      The photographs of the cross sections were digitized using an image scanner and
      the contours of the external surface of the teeth, the obturated root canals and
      the boundaries of dye penetration were followed. Finally, a three-dimensional
      surface representation was achieved using the triangulation method. RESULTS:
      Although the sample size and the experimental methods were not designed to form
      valid groups, the results showed that all roots obturated with Ketac-Endo sealer
      had dye microleakage, whilst only three teeth of the Roth's 801 group had dye
      microleakage. CONCLUSIONS: The 3D reconstruction of dye microleakage proved to be
      an interesting method and a useful tool for the evaluation of coronal
      microleakage when using different types of root canal sealers.

PMID- 11307443
TI  - Shaping ability of Hero 642 rotary nickel-titanium instruments in simulated root
      canals: Part 1.
AB  - AIM: To determine the general efficacy and shaping ability of Hero 642 nickel
      titanium rotary instruments during the preparation of simulated canals. Part 1 of
      this two-part report describes the efficacy of the instruments in terms of three
      dimensional canal form. METHODOLOGY: A total of 40 simulated root canals made up
      of four different shapes in terms of angle and position of curvature were
      prepared by Hero 642 instruments using a crown-down preparation sequence. The
      efficacy of the instruments was assessed in terms of preparation time, instrument
      failure, canal blockages and loss of canal length. Intra-canal impressions were
      taken of the prepared canals in order to assess three-dimensional canal form.
      RESULTS: The mean time for canal preparation was 8.6 min and was influenced
      significantly (P < 0.05) by canal shape. Two instruments fractured and eight
      instruments deformed; significant differences were observed between canal shapes
      (P < 0.05). All of the canals remained patent. Fifteen canals (39.5%) maintained
      the correct working distance, 15 lost distance and eight canals gained length.
      Examination of intracanal impressions demonstrated that the majority of canals
      (79%) had apical stops; canal shape had a significant influence (P < 0.001) on
      the quality of apical stops. With one exception all canals had smooth canal walls
      and all of the canals showed good flow characteristics. Taper was poor in 30
      canals (79%) and good in eight canals (21%). CONCLUSIONS: Hero 642 rotary nickel
      titanium instruments prepared simulated canals rapidly but with a three
      dimensional form that lacked adequate taper.

PMID- 11307444
TI  - Shaping ability of Hero 642 rotary nickel-titanium instruments in simulated root
      canals: Part 2.
AB  - AIM: To determine the shaping ability of Hero 642 nickel-titanium rotary
      instruments during the preparation of simulated canals. METHODOLOGY: A total of
      40 simulated root canals made up of four different shapes, in terms of angle and
      position of curvature, were prepared by Hero 642 instruments using a crown-down
      preparation sequence. Pre- and postoperative images of the canals were taken
      using a video camera attached to a computer with image analysis software. The pre
      and postoperative views were superimposed to highlight the amount and position
      of material removed during preparation. This report describes the efficacy of the
      instruments in terms of prevalence of canal aberrations, the amount and direction
      of canal transportation and overall postoperative shape. RESULTS: Four zips and
      four elbows were created during preparation, all in canals with 40 degrees, 12 mm
      curves. No perforations or danger zones were created. Highly significant
      differences (P < 0.001) were apparent between the canal shapes in total canal
      width at the apex and beginning of the curve, and in the amount of resin removed
      from the inner and outer aspects of the curve at the orifice. Canal
      transportation was most frequently directed toward the outer aspect of the curve
      at specific points along the canal, except at the orifice, where it was apparent
      that canals with 20 degrees curves transported toward the inner. Overall, mean
      absolute transportation was always less than 0.15 mm; however, significant
      differences occurred between canal shapes at the end-point (P < 0.01), apex of
      the curve (P < 0.01) and at the orifice (P < 0.01). CONCLUSIONS: Under the
      conditions of this study, Hero 642 rotary nickel-titanium instruments created
      canals with few aberrations and no perforations. The relatively high proportion
      of aberrations in canals with short, acute curves may indicate that instruments
      with increased taper should be used with caution at or near the full working
      distance. Further research in real teeth is necessary to elucidate the full
      potential of these new rotary instruments for use in root canal preparation.

PMID- 11307445
TI  - Cleaning efficacy of two apical preparation regimens following shaping with hand
      files of greater taper.
AB  - AIM: The aim of this investigation was to assess canal cleaning following shaping
      with hand files of greater taper. METHODOLOGY: Thirty mesial canals and 30 distal
      canals in mandibular molars were prepared with .08 and .10 hand files of greater
      taper, respectively. Following initial preparation, 0.02 instruments were used
      incrementally shorter in a stepback manner. In half the canals instrumentation
      was performed to size 35 1 mm short of the canal terminus. In the other half the
      series was continued through to size 60 using stepback increments of half to one
      millimetre as appropriate (foramen size was maintained at size 20 in all groups).
      Sodium hypochlorite (4.5%) and REDTA (17%) were used as irrigants for all groups.
      Cleaning efficacy was evaluated by scoring the amount of remaining debris using a
      light microscope (x50) and calibrated eyepiece micrometer (range 0-3). RESULTS:
      Canals stepped back through to a size 60 were significantly cleaner than those
      instrumented to a size 35 only (Mann-Whitney P < 0.05). CONCLUSION: Refining the
      apical region of canal preparation by stepping back through to a size 60 reduced
      remaining debris following shaping with files of greater taper.

PMID- 11307446
TI  - Effects of pulsed Nd:YAG laser irradiation on smear layer at the apical stop and
      apical leakage after obturation.
AB  - AIM: This study evaluated the removal of smear layer at the apical stop by pulsed
      Nd:YAG laser irradiation with or without black ink, and the degree of apical
      leakage after obturation in vitro. METHODOLOGY: Sixty extracted human single
      rooted teeth were used in this study. The teeth were instrumented up to a size 40
      K-file, and then divided into three groups of 20 teeth each: group 1 was unlased
      as a control group; group 2 was treated with a laser; group 3 was treated with a
      laser and black ink. The laser was operated at 2 W and 20 pp for 2 s, and
      irradiation was performed twice with a 30-s interval. In each group, 10 teeth for
      the leakage study were obturated and immersed in rhodamine B solution for 48 h at
      37 degrees C, and the others were used for evaluation of remaining smear layer.
      All teeth were bisected longitudinally and observed by stereoscopy or scanning
      electron microscopy. RESULTS: The smear layer in the laser-treated groups almost
      melted or evaporated, and was removed significantly compared with the control
      group (P < 0.05). Leakage was observed in 60% of samples in group 1 and in 20% of
      samples in group 2. No leakage was observed in group 3, which was significantly
      different from the control (P < 0.05). CONCLUSIONS: These results suggest that
      pulsed Nd:YAG laser irradiation with black ink increases the removal of smear
      layer compared with that without black ink, and reduces apical leakage after
      obturation significantly.

PMID- 11307447
TI  - Reliability of radiographic observations recorded on a proforma measured using
      inter- and intra-observer variation: a preliminary study.
AB  - AIM: The aim of this preliminary study was to test the reliability of
      radiographic evaluation of features of endodontic interest using a newly devised
      data collection system. METHODOLOGY: Twelve endodontic MSc postgraduate students
      and one specialist endodontist examined sample radiographs derived from a random
      selection of 42 patients seen previously on an Endodontic New Patient Clinic
      (EDI). Each student examined a random selection of 8-9 roots on periapical
      radiographs of single- and multirooted teeth, with and without previous root
      canal therapy and 3-4 dental panoramic tomograms (DPTs). A total of 100 roots
      were examined. A proforma was used to record observations on 67 radiographic
      features using predefined criteria. Intra-observer agreement was tested by asking
      the students to re-examine the radiographs. The principle investigator and the
      specialist endodontist examined the same radiographs and devised a Gold Standard
      using the same criteria. This was compared with the student assessments to
      determine inter-observer variation. The postgraduates then attended a revision
      session on the use of the form. Each student subsequently examined 8-9 different
      roots from the pool of radiographs. A further assessment of inter-observer
      variation was made by comparing these observations with the Gold Standard.
      RESULTS: Of the 67 radiographic features, only 25 had sufficient response to
      allow statistical analysis. Kappa values for intra- and inter-observer variation
      were estimated. These varied depending on the particular radiographic feature
      being assessed. Fifteen out of 25 intra-observer recordings showed 'good' or
      'very good' Kappa agreement, but only three out of 25 inter-observer observations
      achieved 'good' or 'very good' values. Inter-observer variation was improved
      following the revision session with 16 out of 25 observations achieving 'good' or
      'very good' Kappa agreement. CONCLUSIONS: Modification to the proforma, the
      criteria used, and training for radiographic assessment were considered necessary
      to improve the accuracy and reproducibility of the observations entered.

PMID- 11307448
TI  - A comparison of two nickel-titanium instrumentation techniques in teeth using
      microcomputed tomography.
AB  - AIM: The aim of the study was to compare the shaping of root canals by two nickel
      titanium instrumentation techniques using microcomputed tomography (MCT).
      METHODOLOGY: Ten mandibular first molar teeth (30 canals) that had intact crowns
      and fully formed roots were scanned using MCT. Fifteen canals were instrumented
      using NiTiFlex hand files (Maillefer) using balanced force. The remainder were
      instrumented using prototype ProFile 0.04 Taper instruments (Dentsply) in a crown
      down manner to an apical size ISO 25. The teeth were scanned again following
      instrumentation. The two instrumentation techniques were compared in a total of
      27 canals. The area of dentine removed at predetermined levels (2.0, 3.0, 4.5,
      6.0, 7.5 mm) from the apex was measured. Transportation and centring were
      recorded. Images constructed at these levels were compared with video images of
      equivalent physical sections created after the second scan. The volume of dentine
      removed in the apical 7.5 mm of the root canals of each tooth was calculated and
      the different techniques compared. Rendered three-dimensional images were used to
      assess the preparations qualitatively. The time taken for preparation was
      recorded. RESULTS: There was no significant difference between hand
      instrumentation with NitiFlex files and machine instrumentation with prototype
      ProFile 0.04 Taper instruments for any of the variables tested. CONCLUSIONS: Both
      techniques produced well centred and tapered preparations.

PMID- 11307449
TI  - Apparent periapical repair without operative intervention: a case report and
      discussion.
AB  - CASE REPORT: A case is described where substantial reduction of an established
      periapical lesion appeared to take place in the absence of operative
      intervention, and as the crown of the tooth was progressively destroyed by dental
      caries. The case raises debate on the pathogenesis, diagnosis and monitoring of
      endodontic lesions, and may stimulate renewed research interest in these most
      fundamental elements of clinical endodontology.

PMID- 11307450
TI  - The preparation of periapical lesions for flow cytometry.
AB  - AIM: To devise an optimal protocol and to analyse the leucocyte composition of
      periapical (PA) lesions by flow cytometry. METHODOLOGY: PA lesions were
      mechanically agitated, with and without proteolysis. This was with either 0.2%
      collagenase alone, or in combination with 0.02% DNA-ase in serial incubations
      until all tissue was digested. The efficacy of each method was assessed by
      counting total cell yield and cell viability. Phenotype stability was gauged by
      the percentage of peripheral blood leucocytes (PBL) which expressed CD45RB, CD3,
      CD20, CD4 and CD8 before and after mechanical and collagenase treatment. RESULTS:
      Disaggregation of PA lesions was superior if collagenase was present, but cell
      clumping was problematic unless the DNA-ase was also added, and serial digestion
      with this combination produced optimal cell yield and viability. Nevertheless,
      the total number of cells released rarely exceeded 105, though viability was in
      excess of 80%. Mechanical agitation and proteolysis adversely affected PBL
      phenotypes, but collagenase digestion limited to 10 min caused least damage. Flow
      cytometric analysis of disaggregated PA lesions failed to identify more than 7.9%
      (mean, range 6-10%) CD45RB + cells. CONCLUSIONS: Because of the necessity for
      single cell suspensions, flow cytometry is not easily applied to the analysis of
      leucocytes in PA lesions, and further refinements in tissue disaggregation and
      cell preparation are required.

PMID- 11307451
TI  - Periapical health related to the quality of root canal treatment in a Belgian
      population.
AB  - AIM: The aim of this study was to collect data on the prevalence and technical
      standard of root canal treatment as well as the prevalence of apical
      periodontitis in Belgium. METHODOLOGY: The panoramic radiographs of 206 Belgian
      adults attending the Dental School of the University Hospital of Gent were
      examined for endodontic treatment, periapical conditions and coronal
      restorations. RESULTS: Of the 4617 teeth examined, 6.8% were endodontically
      treated. Periapical radiolucencies were found in 6.6% of all teeth and in 40.4%
      of the endodontically treated teeth. More than half of the root-filled teeth
      (56.7%) were scored inadequate on the basis of a criterion evaluating the level
      of the root canal filling. CONCLUSION: The endodontic treatment need of this
      Belgian subpopulation was great and the technical standard of root canal
      treatment disappointing. The findings indicate that there is still a substantial
      need for postgraduate endodontic education in Belgium and a need for specialists
      in endodontology.

PMID- 11307452
TI  - Diminished leakage along root canals filled with gutta-percha without sealer over
      time: a laboratory study.
AB  - AIM: The aim of this study was to investigate the long-term seal of gutta-percha
      (GP) without sealer. METHODOLOGY: Extracted human maxillary central incisors were
      prepared and obturated using heat- or chloroform-softened GP only, or GP in
      combination with a root canal sealer. Leakage along root fillings was measured at
      48 h and after a period of 6 months using a fluid transport model. RESULTS: At 48
      h the GP-filled roots without sealer leaked more than the control roots filled
      with GP and sealer (P < 0.0001). At 6 months a significant reduction in leakage
      was found in the GP-only groups (P < 0.05 for both heat- and chloroform-softened
      GP). After 6 months, roots filled by vertical condensation of GP-only had similar
      leakage as vertically condensed GP with a sealer (P > 0.05). CONCLUSIONS: The
      long-term seal of root fillings is affected by the volume change of both GP and
      sealer. Leakage reduction due to expansion of GP may compensate to a certain
      extent for leakage that may occur from sealer dissolution.

PMID- 11307453
TI  - Inactivation of local root canal medicaments by dentine: an in vitro study.
AB  - AIMS: The aim of the study was to investigate the inactivation by dentine of the
      antibacterial activity of various commonly used local root canal medicaments.
      METHODOLOGY: The medicaments tested were saturated calcium hydroxide solution, 1%
      sodium hypochlorite, 0.5% and 0.05% chlorhexidine acetate, and 2/4% and 0.2/0.4%
      iodine potassium iodide. Dentine was sterilized by autoclaving and crushed into
      powder with a particle size of 0.2-20 microns. Aliquots of dentine suspension
      were incubated with the medicaments in sealed test tubes at 37 degrees C for 24 h
      or 1 h before adding the bacteria. In some experiments bacteria were added
      simultaneously with dentine powder and the medicament. Enterococcus faecalis
      A197A was used as a test organism. Samples for bacterial culturing were taken
      from the suspensions at 5 min, 1 h and 24 h after adding the bacteria. RESULTS:
      Dentine powder had an inhibitory effect on all medicaments tested. The effect was
      dependent on the concentration of the medicament as well as on the length of the
      time the medicament was preincubated with dentine powder before adding the
      bacteria. The effect of calcium hydroxide on E. faecalis was totally abolished by
      the presence of dentine powder. Similarly, 0.2/0.4% iodine potassium iodide lost
      its effect after preincubation for 1 h with dentine before adding the bacteria.
      The effect of 0.05% chlorhexidine and 1% sodium hypochlorite on E. faecalis was
      reduced but not totally eliminated by the presence of dentine. No inhibition
      could be measured when full strength solutions of chlorhexidine and iodine
      potassium iodide were used in killing E. faecalis. CONCLUSIONS: The dentine
      powder model appears to be an efficient tool for the study of interactions
      between local endodontic medicaments, dentine, and microbes.

PMID- 11307454
TI  - Determination of endotoxins in caries: association with pulpal pain.
AB  - AIM: The aims of this study were: (i) to determine the presence or absence of
      endotoxins in the superficial and deep layers of carious lesions of symptomatic
      and asymptomatic teeth with vital pulps; (ii) to quantify the amount of endotoxin
      present; and (iii) to associate the presence of endotoxins with the acute pulpal
      pain derived from the irreversible pulpitis. METHODOLOGY: Two specimens of
      carious dentine were taken under aseptic conditions from symptomatic teeth with
      irreversible pulpitis (n = 9) and asymptomatic teeth with reversible pulpitis (n
      = 11). The first specimen was taken from a layer of superficial caries and the
      second from a deeper one. Sound dentine was also collected from intact teeth
      without restoration and used as a noncarious control group (n = 4). During the
      patient sampling procedure an effort was made to collect an equal quantity of
      caries and sound dentine in all cases (approximately 6 mg). The extraction of
      endotoxins was performed using the Phenol-water method. The assay and
      quantitative determination of endotoxins was performed by the Quantitative
      Chromogenic test using Limulus Lysate. Data were analysed statistically using
      either independent or paired t-tests. RESULTS: The results indicated that
      endotoxins were present in the superficial and deep layers of caries of all
      symptomatic teeth with irreversible pulpitis (0.15078 and 0.12111 ng mL-1,
      respectively), with significantly greater amount (P < 0.01) in the superficial
      compared to the deep layer. Endotoxins were found in superficial and deep layer
      of caries of all asymptomatic teeth with reversible pulpitis (0.12091 and 0.07163
      ng mL-1, respectively), with significantly greater amounts (P < 0.001) in the
      superficial compared to the deep layer. The results also demonstrated that
      significantly greater concentrations (P < 0.005) of endotoxins were present in
      the superficial carious layer of symptomatic compared with asymptomatic teeth
      (0.15078 and 0.12091 ng mL-1, respectively). Likewise, significantly greater
      amounts (P < 0.001) of endotoxins were present in the deep carious layer of
      symptomatic compared with asymptomatic teeth (0.12111 and 0.07163 ng mL-1,
      respectively). In sound dentine no endotoxins were detected. CONCLUSIONS: This
      study demonstrates that endotoxins are present in carious lesions of symptomatic
      and asymptomatic teeth. The amount of endotoxin was significantly greater in the
      superficial compared to the deep layer of carious dentine. More endotoxins are
      present in caries of painful teeth compared with those without symptoms.

PMID- 11307455
TI  - Four second molars with single roots and single canals in the same patient.
AB  - CASE REPORT: Studies on canal configuration have demonstrated a substantial
      variation in the number of roots and root canals in different teeth. Maxillary
      and mandibular molars may have three and two roots, respectively, and generally
      present with three of four root canals. This case describes the presence of one
      single root and one root canal in all second molars of the same patient.

PMID- 11307456
TI  - Prognosis in periradicular surgery: a clinical prospective study.
AB  - AIM: The purpose of this prospective study was to evaluate the prognosis of
      periradicular surgery using well-defined case selection and a rigorous surgical
      protocol. METHODOLOGY: Teeth to be treated surgically demonstrated a
      periradicular lesion of strictly endodontic origin with or without clinical signs
      and symptoms of inflammation. A total of 114 teeth were treated. Following the
      reflection of a full mucoperiosteal tissue flap, residual soft tissues were
      curetted, root ends were resected with a fine high-speed diamond bur, root-end
      cavities were prepared ultrasonically with diamond tips, and IRM root-end
      fillings were placed. Cases were followed clinically and radiographically for a
      period ranging from 1 to 4 years. RESULTS: The results of this study showed 91.2%
      success out of a total of 102 teeth available for follow-up, based on accepted
      parameters of evaluation. Cases were considered successful if there were no
      clinical signs or symptoms present and there was radiographic evidence of
      complete or incomplete healing (scar tissue). Factors related to case selection,
      parameters of healing and surgical technique are discussed in relation to the
      success rate identified in this prospective study. CONCLUSIONS: Adherence to a
      strict endodontic surgical protocol and the use of contemporary techniques and
      materials will result in a predictably successful outcome in a wide range of
      teeth.

PMID- 11307457
TI  - CD57+ cells in radicular cyst.
AB  - AIM: As CD57 antigen is an important modulator of the immune system, the purpose
      of the present study was to compare the expression of this antigen on radicular
      cysts (RC) with hyperplastic or atrophic epithelium. METHODOLOGY: Twenty cases of
      RC were retrieved and classified as atrophic or hyperplastic. A biotin
      streptavidin amplified system was used for identification of the CD57 receptor.
      RESULTS: The results demonstrated a greater percentage of CD57+ cells in RC with
      atrophic epithelium compared to hyperplastic epithelium. CONCLUSION: As the
      expression of CD57 is indicative of immunosuppression, it may constitute a
      negative immunomodulator of RC's epithelium growth. Further studies are necessary
      to understand the importance of this cell to the biological activity or
      inactivity of RC's epithelium development.

PMID- 11307458
TI  - Root canal anatomy of maxillary first and second permanent molars.
AB  - AIM: The aim of this investigation was to study the root canal anatomy of
      maxillary first and second molar teeth from an Irish population sample using a
      clearing technique. METHODOLOGY: Eighty-three extracted permanent maxillary right
      first molars and 40 permanent right maxillary second molars were included in this
      investigation. The specimens were demineralized and then cleared using methyl
      salicylate. The following observations were made: number of roots, prevalence of
      fusion, types of root canals using Vertucci's classification, presence and
      position of lateral canals, presence and position of transverse anastomoses,
      number and position of apical foramina and the frequency of occurrence of apical
      deltas. RESULTS: Eleven per cent of maxillary first molars and 43% of maxillary
      second molars had fused roots. A total of 78% of mesiobuccal roots in maxillary
      first and 58% in maxillary second molars had two canals. Sixty-two per cent of
      maxillary first and 50% of maxillary second molars had two apical foramina. There
      was a significant inverse relationship between age and the occurrence of two
      canals and between age and the occurrence of transverse anastomoses in both tooth
      morphotypes (P < or = 0.05). CONCLUSIONS: It is concluded that a significant
      proportion of the first and second molar specimens studied had two canals in the
      mesiobuccal root (78% and 58%, respectively) and that the occurrence of two
      canals and transverse anastomoses decreased significantly with increasing age.

PMID- 11307459
TI  - Comparison of cold lateral condensation and a warm multiphase gutta-percha
      technique for obturating curved root canals.
AB  - AIM: The aim of this project was to evaluate and compare the radiographic quality
      and sealability of root fillings in extracted human teeth using lateral
      condensation of gutta-percha or multiphase gutta-percha obturation (Alphaseal).
      METHODOLOGY: A total of 108 freshly extracted human, mature single-rooted teeth
      were divided into two identical groups of 54 teeth on the basis of root canal
      shape. The canals were prepared to a minimum 0.055 taper and enlarged to size 35
      at the apex. All root canals were flushed with 17% EDTA solution and 2.5% NaOCl
      to remove the dentinal smear layer. The canals of one group were obturated using
      cold lateral condensation of gutta-percha and the canals of the other group were
      filled using a warm multiphase gutta-percha obturation technique. The extrusion
      of sealer and/or gutta-percha through the apex of the teeth was recorded using a
      simple yes/no scheme. The sealability of each technique was assessed by a dye
      penetration method. The radiographic quality of obturation was determined for
      each canal using a four-point scale. RESULTS: Root canals filled by multiphase
      obturation had significantly more extrusion of sealer (P < 0.001) and gutta
      percha (P < 0.001) than canals filled by lateral condensation. Canals filled by
      multiphase gutta-percha obturation had significantly less apical dye leakage than
      those obturated by lateral condensation (P < 0.05). Lateral condensation achieved
      significantly better scores for radiographic quality than multiphase obturation
      from the bucco-lingual view (P < 0.01). CONCLUSIONS: Under laboratory conditions
      multiphase gutta-percha had better sealability but poorer radiographic quality
      than lateral condensation.

PMID- 11307460
TI  - TGF-beta 1 alone and in combination with calcium hydroxide is synergistic to TGF
      beta 1 production by osteoblasts in vitro.
AB  - AIM: To examine the effects of calcium hydroxide (Ca(OH)2), transforming growth
      factor-beta (TGF-beta 1), and Ca(OH)2/TGF-beta 1 coadministration on TGF-beta 1
      and interleukin-6 (IL-6) synthesis by early (subculture 1) and late (subculture
      5) osteoblast cultures. METHODOLOGY: Early and late cultures were established
      using bone cells harvested from 21-day-old fetal rat calvaria. Cell cultures of
      both early and late osteoblasts were divided into four groups: group 1, control;
      group 2, cells challenged with Ca(OH)2; group 3, cells challenged with TGF-beta
      1; and group 4, cells challenged with Ca(OH)2 and TGF-beta 1 in combination. TGF
      beta 1 and IL-6 levels for all groups were determined using ELISA methodology.
      RESULTS: ANOVA and Tukey HS analyses revealed that osteoblasts of groups 3 and 4
      significantly increased (P < 0.001) TGF-beta 1 synthesis in both early and late
      cultures of osteoblasts. IL-6 was not detected in any of the groups considered in
      this study. CONCLUSIONS: Exogenous TGF-beta 1 has an autocrine effect on cell
      cultures of osteoblasts. Administration of TGF-beta 1 alone or in combination
      with Ca(OH)2 increases the synthesis of TGF-beta 1 in osteoblast cultures.
      Ca(OH)2 and TGF-beta 1 are compatible when placed in a culture of osteoblasts.
      Ca(OH)2 provides a favourable environment for the anabolic effects of TGF-beta 1.

PMID- 11307461
TI  - Endodontic teaching in Philippine dental schools.
AB  - AIM: The aim of this study was to evaluate the pattern of undergraduate
      endodontic teaching in Philippine dental schools. METHODOLOGY: Data were gathered
      by sending questionnaires to the deans of the 23 dental schools in the country to
      determine details of the teaching of root canal treatment in permanent teeth. The
      covering letter requested that endodontic staff complete the questionnaire.
      RESULTS: Twenty of 23 dental schools returned completed questionnaires.
      Similarities were observed in the timing of undergraduate endodontic teaching,
      working length determination, and root canal preparation technique. Irrigating
      fluids recommended included one or a combination of the following: sodium
      hypochlorite, hydrogen peroxide, distilled water and EDTA. The root canal
      medicaments popularly employed were CMCP and eugenol. Most schools used slow
      setting zinc oxide eugenol cement as sealer. Differences between schools were
      noted in the laboratory component of the course. The time allotted for the
      laboratory exercises, as well as the number of teeth used, differed greatly
      between each school. An inadequate tutor to student ratio was noted in the
      majority of schools. Teaching aids were limited and, in most instances, produced
      by faculty members. Most faculty members teaching endodontics had no specialist
      training. CONCLUSION: The results of this study have demonstrated that there is a
      need to review endodontic teaching in the majority of the Philippine dental
      schools to ensure that the course content and curriculum employed by all schools
      meet specified standards and that appropriate measures should be considered to
      enhance the learning experience of students.

PMID- 11307462
TI  - Use of rubber dam and irrigant selection in UK general dental practice.
AB  - AIM: To evaluate factors which influence rubber dam use and irrigant selection in
      UK National Health Service (NHS) endodontics. METHODOLOGY: A postal survey was
      conducted amongst two age cohorts of dentists, representing all of the 1970-73
      (older) and 1990-93 (younger) graduates of two northern English dental schools (n
      = 643). Key and supplementary questions were posed on levels of rubber dam use,
      irrigant selection, and factors influencing practice in NHS endodontics. After
      manual checking, validated (dual) entry of responses was made to a flat ASCII
      data file before analysis with SPSS software. The threshold for statistical
      significance was set at the 95% probability level. RESULTS: Eighty-five per cent
      of the valid sample responded to the questionnaire. Regardless of age and
      qualifying school, less than one-fifth of dentists always or frequently used
      rubber dam, whilst 60% never used it. Qualifying school had a significant
      influence on rubber dam use, whilst age had a variable influence. Major
      disincentives to the use of rubber dam included the perception that patients do
      not like it, that the NHS fee was inadequate to justify its use, that it took too
      long to apply, and that dentists had received inadequate training. Frequent users
      of rubber dam were significantly less likely to cite these disincentives than
      nonusers. Overall, local anaesthetic solution was the most common endodontic
      irrigant. Irrigant choice was strongly linked to rubber dam use, and to
      graduation cohort. Seventy-one per cent of rubber dam users irrigated with sodium
      hypochlorite, compared with only 38% of nonusers. This pattern was reversed for
      local anaesthetic irrigation. Younger graduates were significantly more likely to
      irrigate with local anaesthetic solution than their older counterparts, and the
      younger graduates of one school showed a highly significant increase in the use
      of chlorhexidine. CONCLUSIONS: 1) The majority of UK Health Service dentists
      never use rubber dam isolation in endodontic treatment. 2) Qualifying school has
      a significant impact on rubber dam use, and irrigant selection. 3) Use of rubber
      dam has a significant association with irrigant choice in endodontics.

PMID- 11307463
TI  - Computerized infrared thermographic imaging and pulpal blood flow: Part 1. A
      protocol for thermal imaging of human teeth.
AB  - AIM: To observe the thermographic appearance of teeth and to develop a suitable
      protocol for imaging teeth in human subjects using modern thermographic imaging
      (TI) equipment in a thermologically controlled environment. METHODOLOGY: The
      emissivity of enamel was investigated using an extracted incisor tooth. A total
      of 12 unrestored maxillary lateral incisors in six healthy patients were then
      imaged under rubber dam after a 20-min equilibration period and the thermographic
      data analysed using a dedicated software package. Recordings were made from
      standardized gingival and incisal sites on each tooth and the temperature
      gradient established for each tooth. Subsequently, a sequence of images of both
      maxillary central incisors in one patient was stored every 30 s during a 20-min
      equilibration period with and without an air-conditioning unit in operation.
      RESULTS: For the lateral incisors there was a consistent temperature gradient
      (mean 1.28 degrees C) from gingival area to incisal area and there were no
      statistically significant differences between right and left sides for the
      gingival site (t = 0.34, NS) or the incisal site (t = 0.62, NS). The air
      conditioning unit had a rapid and profound cooling effect. With the air
      conditioning disabled there was a mean tooth surface temperature increase of 1.1
      degrees C from 0 to 5 min of the equilibration period and 0.3 degree C from 15 to
      20 min. CONCLUSIONS: There was no significant difference in gingival or incisal
      temperatures between pairs of contralateral maxillary lateral incisors and a
      consistent temperature gradient existed from gingival to incisal areas of healthy
      maxillary lateral incisor teeth. The protocol described is suitable for TI of
      vital teeth. However, TI measured tooth surface temperature only which was
      extremely sensitive to air currents. A 15-min acclimatization period under rubber
      dam was adequate to allow stable tooth surface temperature measurement.

PMID- 11307465
TI  - Efficacy of Quantec rotary instruments for gutta-percha removal.
AB  - AIM: The purpose of this study was to evaluate Quantec SC rotary instruments for
      removal of gutta-percha during retreatment of straight root canals. METHODOLOGY:
      The root canals of 30 central incisors were instrumented and obturated before the
      teeth were randomly divided into three groups of 10 specimens each. Quantec SC
      rotary instruments and a 16:1 reduction handpiece powered by an electric motor
      were then used to remove the gutta-percha and sealer from canals. A different
      speed was used in each group (group 1, 350 r.p.m.; group 2, 700 r.p.m.; and group
      3, 1500 r.p.m.). The followings factors were evaluated: time taken to reach
      working length, time for gutta-percha removal, total time, apically extruded
      material during filling removal and number of fractured instruments. Radiographs
      were taken after the filling removal and after the canal wall cleanliness was
      evaluated. The teeth were grooved longitudinally, divided, and the walls of each
      half were evaluated visually for cleanliness. They were then digitized using a
      scanner and the residual debris measured. RESULTS: The group in which a speed of
      1500 r.p.m. was used had significantly faster treatment than the other groups.
      The amount of apically extruded material was not significantly different between
      groups. The only significant difference between groups for canal cleanliness was
      the middle third by radiographic evaluation: the group of 350 r.p.m. had larger
      amount of debris than the others. In group 1, six instruments fractured; in group
      2, four instruments fractured; and in group 3, one instrument fractured.
      CONCLUSIONS: Cleanliness and residual debris were equivalent for each group, but
      the use of 1500 r.p.m. speed was more rapid and fewer instruments fractured.

PMID- 11307464
TI  - Computerized infrared thermographic imaging and pulpal blood flow: Part 2.
      Rewarming of healthy human teeth following a controlled cold stimulus.
AB  - AIM: To investigate the rewarming pattern and rewarming rate of clinically
      healthy teeth following a controlled cold stimulus using TI techniques.
      METHODOLOGY: A controlled cold stimulus was developed using an air stream at 20
      degrees C. Gingival and incisal sites on 12 healthy maxillary lateral incisors in
      six patients were imaged under rubber dam following 20 s cooling. Images were
      captured at 10 s intervals during a 3-min rewarming period and the data used to
      construct graphs of the rewarming rate. Log transformation of the data was used
      to produce 'best fit' straight line graphs. Linear regression analysis was used
      to examine three variables, viz. the side of the mouth (right or left), the site
      of measurement (gingival or incisal) and the phase of rewarming (early 0-90 s,
      late 91-180 s). RESULTS: The mean temperature change (delta t degree C) during
      rewarming was 8.5 degrees C (SD 1.0 degree C) for gingival sites and 7.2 degrees
      C (SD 1.1 degrees C) for incisal sites. The slope of the 'best fit' straight line
      data enabled a rewarming index to be calculated for each site on each tooth.
      Linear regression analysis showed that the phase of rewarming was highly
      significant but the other variables were not. A one-way ANOVA showed no
      significant differences between or within groups. CONCLUSIONS: Three min is an
      appropriate time to record rewarming of teeth cooled for 20 s with an airstream
      at 20 degrees C. The side or site used to record surface temperatures using this
      technique is not significant. Rewarming is exponential and log transformation of
      the data produces a well-fitting straight line graph. The slope of this line
      provides a rewarming index which should enable comparison of TI and laser Doppler
      flowmetry in determining pulpal blood flow as a measure of tooth vitality.

PMID- 11307466
TI  - Mandibular first molar with three distal root canals.
AB  - CASE REPORT: A right mandibular first molar requiring root canal treatment was
      found to have one mesial and two distal roots and a total of five canals. The
      mesial and distobuccal root had two separate canals; the distolingual root had
      one. This case demonstrates a rare anatomical configuration and supplements
      previous reports of the existence of such configurations in mandibular first
      molars.

PMID- 11307467
TI  - Lateral breakdown of nonendodontic origin adjacent to maxillary left incisors.
AB  - CASE REPORT: A 16-year-old female presented with a labial fistula located between
      the central and lateral left maxillary incisors. The teeth had normal colour,
      responded positively to pulp testing, demonstrated negative percussion tests and
      had no evidence of periodontal pockets. The patient reported no history of
      trauma, but mentioned that she had received orthodontic treatment. Radiographic
      examination showed bone loss between these two teeth. Explorative surgery
      followed by antibiotic treatment was performed, but a fistula reappeared after 22
      months. Surgical retreatment combined with antibiotic treatment resulted in
      gradual healing over a three-year period. No root canal treatment was performed.
      Aetiological considerations connected to tissue injury and inflammation are
      discussed. Inflammation induced disturbances in local homeostasis may possibly
      explain the lateral breakdown of bone. Such areas of reduced resistance may,
      under unfavourable conditions, be infected by blood-born pathogens. Information
      about such aberrant cases is important in endodontic decision making.

PMID- 11307468
TI  - Root canal treatment and general health: a review of the literature.
AB  - REVIEW: The focal infection theory was prominent in the medical literature during
      the early 1900s and curtailed the progress of endodontics. This theory proposed
      that microorganisms, or their toxins, arising from a focus of circumscribed
      infection within a tissue could disseminate systemically, resulting in the
      initiation or exacerbation of systemic illness or the damage of a distant tissue
      site. For example, during the focal infection era rheumatoid arthritis (RA) was
      identified as having a close relationship with dental health. The theory was
      eventually discredited because there was only anecdotal evidence to support its
      claims and few scientifically controlled studies. There has been a renewed
      interest in the influence that foci of infection within the oral tissues may have
      on general health. Some current research suggests a possible relationship between
      dental health and cardiovascular disease and published case reports have cited
      dental sources as causes for several systemic illnesses. Improved laboratory
      procedures employing sophisticated molecular biological techniques and enhanced
      culturing techniques have allowed researchers to confirm that bacteria recovered
      from the peripheral blood during root canal treatment originated in the root
      canal. It has been suggested that the bacteraemia, or the associated bacterial
      endotoxins, subsequent to root canal treatment, may cause potential systemic
      complications. Further research is required, however, using current sampling and
      laboratory methods from scientifically controlled population groups to determine
      if a significant relationship between general health and periradicular infection
      exists.

PMID- 11307469
TI  - Dissolution of root canal sealer cements in volatile solvents.
AB  - AIM: There are few published data on the solubility profiles of endodontic
      sealers in solvents commonly employed in root canal retreatment. This study
      tested the hypothesis that root canal sealer cements are insoluble in the
      volatile solvents chloroform and halothane. METHODOLOGY: Standardized samples (n
      = 5) of glass ionomer (Ketac Endo), zinc oxide-eugenol (Tubli-Seal EWT), calcium
      hydroxide (Apexit) and epoxy resin (AH Plus) based sealers were immersed in
      chloroform or halothane for 30 s, 1 min, 5 min and 10 min. Mean loss of weight
      was plotted against time of exposure, and differences in behaviour assessed by
      multiple paired t-tests (P < 0.01). RESULTS: Clear differences were shown in the
      solubility profiles of major classes of root canal sealer cements in two common
      volatile solvents. In comparison with other classes of material, Ketac Endo was
      the least soluble in chloroform and halothane (P < 0.01), with less than 1%
      weight loss after 10 min exposure to either solvent. Apexit had low solubility
      with 11.6% and 14.19% weight loss after 10 min exposure to chloroform and
      halothane, respectively. The difference between solvents was not significant (P >
      0.01). Tubli-Seal EWT was significantly less soluble in halothane than chloroform
      (5.19% and 62.5% weight loss after 10 min exposure, respectively (P < 0.01)). Its
      solubility in halothane was not significantly different from that of Apexit. AH
      Plus was significantly more soluble than all other materials in both chloroform
      and halothane (96% and 68% weight loss after 10 min exposure, respectively (P <
      0.01)). CONCLUSIONS: There are significant differences in the solubility profiles
      of major classes of root canal sealer in common organic solvents. Efforts should
      continue to find a more universally effective solvent for use in root canal
      treatment.

PMID- 11307470
TI  - Evaluation of apical sealing of three endodontic sealers.
AB  - AIM: The apical sealing ability of three different endodontic sealers was
      evaluated in extracted teeth using dye penetration. METHODOLOGY: The root canals
      of 99 extracted human maxillary central incisors were prepared sequentially 2 mm
      beyond the apical foramen with a size 55 Nitiflex file. The teeth were divided
      into three experimental groups and obturated by lateral condensation of cold
      gutta-percha and one of the following sealers: group 1, zinc oxide and eugenol
      sealer (Fill Canal); group 2, glass ionomer sealer (Ketac-Endo) and group 3,
      epoxy resin sealer (AH Plus). The teeth were covered with nail varnish to within
      1 mm of the apical foramen and immersed in 2% methylene blue in a reduced
      pressure environment for 24 h. After this period, the teeth were washed and cut
      longitudinally for apical leakage analysis. The values were obtained from the
      maximum depth of leakage as well as the average between the maximum and minimum
      values observed for each group. RESULTS: Statistical evaluation of the results
      showed no significant difference in the leakage between Fill Canal and Ketac-Endo
      (P > 0.05). Leakage with AH Plus was significantly less (P < 0.01) than with the
      other sealers. CONCLUSIONS: All three sealers allowed some leakage to occur.
      Leakage with AH Plus was significantly different than with Fill Canal or Ketac
      Endo.

PMID- 11307471
TI  - Penetration of bacteria in bovine root dentine in vitro.
AB  - AIM: The aim of this study was to develop a test model to quantify the
      penetration of bacteria into dentinal tubules. METHODOLOGY: The model consisted
      of two compartments separated by a bovine dentine specimen with a thickness of
      1.5-3.1 mm. The root cementum was removed from the root surface and the specimens
      were oriented in the model with the pulpal side facing the inoculated chamber of
      the test model. One compartment contained the test organism and the other was
      filled with sterile broth that was evaluated for growth of the test organism. The
      depth of bacterial penetration was measured in the dentine with or without a
      smear layer using both a histological and a quantitative recovering grinding
      technique, after 6 weeks of exposure to the microorganisms. RESULTS: E. faecalis
      penetrated dentine significantly deeper than A. israelii (P < 0.001). After
      removal of the smear layer with EDTA, E. faecalis penetrated significantly deeper
      than in dentine pretreated with saline only (P < 0.01) or with a combination of
      saline and sodium hypochlorite (P < 0.01). Microorganisms were found in 89% of
      the cultured specimens and in 80% of the specimens that were evaluated with light
      microscopy. Total penetration through the dentine specimen and infection of the
      broth in the test compartment of the model occurred in only two out of 72
      specimens. CONCLUSION: Collection and immediate culturing of infected dentine
      dust and counting colony forming units (CFU) allowed an overview of the number of
      bacteria per sample and was more sensitive than microscopy. Removal of the smear
      layer enhanced bacterial penetration.

PMID- 11307472
TI  - Analysis of the healing response to gutta-percha and Diaket when used as root-end
      filling materials in periradicular surgery.
AB  - AIM: To analyse the healing response to gutta-percha and Diaket when used as root
      end filling materials in periradicular surgery. METHODOLOGY: Periradicular
      surgery was completed using the mandibular second, third and fourth premolar
      teeth from nine male mongrel dogs. The six roots on one side of the mouth were
      randomly allocated to one of the following groups: group A: a resected root end
      and a burnished gutta-percha root filling; group B: cavities were prepared to a
      depth of 4.0 mm, using ultrasonic root-end preparation and filled with Diaket.
      The response was evaluated histologically at 55 (nine specimens) and 150 (three
      specimens) days post operatively. RESULTS: The data for the 55-day period was
      analysed statistically using Wilcoxon's Signed Ranks test. No statistical
      analysis was carried out on the 150-day group due to the small number of
      specimens. The level of significance was set at P < 0.05. No statistical
      significance was observed in the healing response between Diaket and gutta-percha
      in the following categories at 55 days: inflammatory response, angiogenesis, root
      end resorption, and cementum deposition. Statistically significant differences
      were observed in the healing categories: bone apposition (P < 0.05) and
      periodontal ligament formation (P < 0.05). CONCLUSIONS: At both time intervals,
      Diaket had a better healing response that was characterized by hard tissue
      formation adjacent to the root-end filling material bordered by occasional
      multinucleated giant cells. The nature of both the hard tissue formation and the
      adjacent cells, however, remains undetermined. Diaket displayed the best healing
      of either material used in this study.

PMID- 11307473
TI  - Effectiveness of 1 mol L-1 citric acid and 15% EDTA irrigation on smear layer
      removal.
AB  - AIM: The aim of this study was to evaluate in vitro the cleansing and smear layer
      removal capability of alternate canal irrigation with citric acid and NaOCl.
      METHODOLOGY: Eighty-one teeth were divided into three groups on the basis of the
      type of instrumentation, namely, manual stainless steel, Ni-Ti mechanized ProFile
      .04 taper or MACXim. The groups were further divided on the basis of irrigation
      protocol: 5% NaOCl alone, NaOCl alternated with 1 mol L-1 citric acid solution or
      a combination of 15% EDTA and Cetrimide solution. After longitudinal sectioning,
      dentinal walls were microphotographed with scanning electron microscopy at x300
      and x1000 magnifications. Qualitative and quantitative cleansing level
      evaluations were performed using computerized image analysis software. Data were
      statistically evaluated using Kruskal-Wallis analysis and t-test. RESULTS:
      Qualitative evaluation at x300 and x1000 showed no statistically significant
      differences in cleansing ability between citric acid, EDTA and NaOCl groups.
      Quantitative evaluation of smear layer removal, measured as open tubules/total
      dentinal surface ratio, showed that 1 mol L-1 citric acid solution was comparable
      to EDTA (11.97% vs. 10.36%) (NS); in samples treated with ProFile .04 taper
      instruments citric acid was most effective (16.17%), whilst in the group treated
      with manual instrumentation EDTA and Cetrimide were the most effective (11.94%).
      Specimens irrigated with 5% NaOCl demonstrated significantly more cleansing than
      those obtained in the other two groups (P < 0.001). CONCLUSIONS: 1 mol L-1 citric
      acid solution was as effective in removing smear layer as EDTA, but was superior
      in specimens treated with ProFile .04 taper instruments.

PMID- 11307474
TI  - Effect of eugenol-containing sealer on marginal adaptation of dentine-bonded
      resin fillings.
AB  - AIM: Eugenol is claimed to interfere with the polymerization of composite resins
      and to affect shear bond strengths of dentine-bonded composite restorations.
      Eugenol-based sealers are used during root canal treatment in teeth that may
      require build-ups or extensive restorations. Unfortunately, the adverse effect of
      eugenol has mostly been assessed in shear bond tests and this variable may be
      clinically inappropriate. The current study evaluate the effect of eugenol in a
      eugenol-based endodontic sealer on marginal adaptation of composite resin
      restorations with and without thermo-mechanical stress. METHODOLOGY: Thirty Class
      V cavities with half of the cavity margins in dentine and half of the cavity
      margins in enamel were prepared in extracted human premolars and then divided
      into 5 groups. Teeth in group 1 were not contaminated with eugenol. Cavities in
      groups 2-4 were contaminated with a eugenol-based sealer (Tubli-Seal, Kerr) and
      cleaned with: (i) sandblasting, (ii) bur finishing alone or (iii) bur finishing
      combined with swabbing with alcohol. These 4 groups were temporized for 6 weeks
      (Ketac, ESPE), whilst group 5 received no eugenol, was not temporized and acted
      as the control. Cavities were restored with Tetric Ceram using Syntac Classic
      (Vivadent) as a dentine-bonding agent. The specimens were then thermo
      mechanically stressed. The percentages of marginal adaptation in dentinal and
      enamel margins were assessed in a SEM at x200 magnification before and after
      stress using a replica method. Mean percentages of marginal adaptation were
      calculated and compared using a two way-ANOVA (influence of eugenol and cleaning
      procedure) and non-parametric tests. RESULTS: Marginal adaptation in enamel
      exceeded 95% and 92% in all specimens before and after thermo-mechanical stress,
      respectively. Before stress, marginal adaptation in dentine ranged from 92.3 +/-
      7.9% to 95.7 +/- 6.2% in groups 1-5. After stress, the percentage of marginal
      adaptation in dentine decreased significantly overall (P < 0.05, range 39.8 +/-
      21.1% to 82.9 +/- 13.7%). The effect of contamination with eugenol was not
      significant (P > 0.05): in contrast, there was a significantly beneficial effect
      when the entire cavity was finished with burs (P < 0.01). CONCLUSIONS: Under the
      conditions of this study, the eugenol containing sealer did not significantly
      impair marginal adaptation in dentinal margins of mixed Class V restorations when
      bur finishing was employed before placement. However, no other cleaning method
      was sufficient to produce acceptable figures of marginal adaptation.

PMID- 11307475
TI  - Radiographic evaluation of periapical healing after obturation of infected root
      canals: an in vivo study.
AB  - AIM: To radiographically compare periapical repair of roots with infected root
      canals obturated in one-step or with calcium hydroxide (Ca(OH)2) intracanal
      medication in two steps. METHODOLOGY: Standardized preoperative periapical
      radiographs were taken of 72 roots of vital dogs' teeth. All roots were then
      aseptically instrumented to ISO size 45. As negative controls, 12 roots were
      aseptically obturated. The remaining roots were infected with dental plaque and
      closed. Six weeks later, apical periodontitis was radiographically confirmed in
      the infected roots. The roots were divided into the following groups: group 1,
      one-step (n = 24); roots were irrigated with 10 cc saline, obturated, and
      permanently restored. Group 2, Ca(OH)2 (n = 24); roots were treated as in group
      1, except that after saline irrigation Ca(OH)2 medicament was placed in the canal
      1 week before obturation. Group 3, positive control (n = 12); the roots were
      irrigated with saline, access permanently closed but canals not obturated. Group
      4, negative control (n = 12); previously aseptically obturated roots were
      permanently restored. After 6 months, standardized postoperative radiographs were
      obtained. Three independent evaluators blinded to the treatment groups evaluated
      the preoperative and postoperative radiographs. The evaluators were instructed to
      rate each root, based on changes on the radiographs, as failed, improved or
      healed. RESULTS: Radiographically, the percentage of cases that completely healed
      were similar for the one-step and Ca(OH)2 groups (35.3% vs. 36.8%). However, the
      Ca(OH)2 group had fewer failed cases (15.8% vs. 41.2%) and more improved cases
      (47.4% vs. 23.5%) than the one-step group. CONCLUSION: Power statistics
      demonstrated that at 43 cases per group, Ca(OH)2 treatment would be statistically
      superior to one-step treatment. We consider this number to be clinically
      important.

PMID- 11307476
TI  - Necrosis of the gingiva caused by calcium hydroxide: a case report.
AB  - CASE REPORT: The present case demonstrates the possible detrimental effect of an
      overextension of a calcium hydroxide intracanal dressing into the periradicular
      and soft tissue after iatrogenic buccal root perforation of a maxillary central
      incisor. At first this perforation was not recognized by the dentist, which
      resulted in the introduction of a large amount of non-setting calcium hydroxide
      paste under the gingival tissues through a dehiscence on the buccal side of the
      root. This report describes the consequences and management of the necrosis of
      the buccal gingiva and mucosa, and the subsequent treatment and follow-up of the
      root perforation.

PMID- 11307477
TI  - Heritable collagen disorders: from genotype to phenotype.

PMID- 11307478
TI  - [Aspects of kidney donation by living donors].

PMID- 11307479
TI  - Metabolic alkalosis in the intensive care unit.

PMID- 11307480
TI  - The Diabetic Foot Project of Flanders, the northern part of Belgium:
      implementation of the St Vincent consensus. Sensibilisation and registration in
      diabetes centres.
AB  - As a result of the St Vincent declaration, a Belgian "task force" was installed
      in 1992 and consequently 16 working groups were formed. They presented their
      objectives in 1995. The working group "prevention and treatment of diabetic foot
      lesions" started the implementation of a screening program to obtain an overview
      of the presentation of diabetic foot lesions, the amputation rate and the
      prevalence of patients with a foot at risk. This study reports the results from
      43 out of 73 Flemish diabetes centres. 1653 patients were enrolled in this study
      (53% women, 47% men, median age 61). 34.6% were type 1 and, 65.4% type 2. One or
      more arterial pedal pulses were absent in 28%, 30.5% had an abnormal monofilament
      test, 35% skin lesions and 28% malformations. Still 19% smoked, 15.8% had visual
      problems and 11% had already developed an ulcer previously. Ulcers were reported
      in 8.7% of which almost 2/3 belonged to Wagner class I. 69 (3.87%) of the
      patients had had amputations. According to the four-risk categories-scale 46.3%
      of the patients belonged to the highest one; peripheral vascular disease,
      previous amputations, previous ulcers, and Charcot joints. In our region we
      didn't have previous data on the prevalence and morbidity of the amputation rate
      with diabetes patients. We observed 3.87% amputations, which is rather high in
      comparison with international data (0.44% - 2.4%). The general follow-up of
      diabetic foot problems can be organised in co-operation with other care
      providers. A national program therefore is going to start in the next months. We
      all have to be aware of the size of the problem to offer the best possible
      prevention. As we have seen, the use of inlay soles and podiatrist-made ortheses
      for example is very low. We hope that all care providers will participate in this
      important project, so that they will acquire a specific attitude towards these
      patients. In daily clinical practice there are some key-roles to be respected by
      all health care providers. In our opinion the next are of the utmost importance:
      take off your diabetic patient's shoes when they visit you; give specific
      education if your patient has a foot at risk; if an ulcer is present, carefully
      follow-up is mandatory and if no good evolution of the ulcer is seen, an early
      referral to a diabetic foot clinic is obvious. Together we can lower down the
      amputation rate of diabetic foot lesions. And that would be a marvelous
      implementation of the St Vincent declaration in Belgium.

PMID- 11307481
TI  - Study of the in vitro activity of amoxicillin/clavulanic acid and other beta
      lactam antibiotics against Escherichia coli isolated from urine specimens.
AB  - A total of 205 serial, unduplicated urinary isolates of Escherichia coli was
      collected from June through August 1998 in 2 community and 3 hospital
      laboratories. By using the NCCLS broth microdilution technique, their in vitro
      susceptibility to ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefuroxime
      axetil, ticarcillin/clavulanic acid and piperacillin/tazobactam was determined.
      One hundred and twenty isolates were from hospitalised patients, 85 from
      ambulatory, 129 community acquired and 76 nosocomial. Half of the nosocomial
      isolates were obtained from naturally produced and half from alternatively
      produced urine specimens. In general, the highest susceptibility rates, following
      NCCLS criteria, were found for piperacillin/tazobactam (93.2%) followed by
      cefuroxime (92.2%) and amoxicillin/clavulanic acid (82.9%). Ampicillin showed a
      clear bimodal distribution with a clear peak for the resistant population. The
      highest degree of ampicillin resistance was found in nosocomial isolates.
      Overall, ampicillin showed the lowest degree of susceptibility. Most of the
      ampicillin resistant isolates remained susceptible to piperacillin/tazobactam,
      cefuroxime and amoxicillin/clavulanic acid. In general, the community acquired
      isolates had higher susceptibility rates than the nosocomial isolates.

PMID- 11307482
TI  - Usefulness of bacteriological surveillance cultures for monitoring infection in
      hospitalized patients: a critical reappraisal.
AB  - Untargeted bacteriological surveillance of superficial and deep body sites is
      frequently performed routinely in various clinical settings. This practice is
      based on the assumption that early identification of surface microbial flora
      might be predictive of organisms that will later cause invasive disease and that
      it may consequently assist in guiding empirical antibiotic therapy. A
      comprehensive review of the literature however indicates that the clinical value
      and cost-effectiveness of such practices still remain debated and appear largely
      unproven in most conditions and situations where they are routinely advocated.
      The present article reviews and critically discusses the available body of
      evidence supporting or disproving the use of bacteriological surveillance
      cultures. It is also aimed to issue general recommendations, strategies and
      methodologies that could be applied in different hospital care settings including
      the neonatal or adult intensive care as well as the hematology-oncology units.

PMID- 11307483
TI  - Progressive bouts of acute abdomen: pet the peritoneum.
AB  - The recent discovery of the mutated gene responsible for Familial Mediterranean
      Fever (FMF) is supposed to facilitate its diagnosis which up till now is a
      clinical one because there are no specific laboratory tests. The sensitivity of
      genetic testing is limited because these tests search only for known mutations.
      In this case report we describe a patient with periodic abdominal pain in whom
      the diagnosis of FMF was wrongly discarded because of lack of a durable effect of
      colchicine and negative genetic testing. Diffuse peritoneal inflammation was
      nicely demonstrated by a FDG-PET (fluoro-deoxy-glucose positron-emission
      tomography) performed during a typical crisis. We discuss the possible diagnostic
      pitfalls and conclude that a crisis-PET might upgrade the level of diagnostic
      certainty in equivocal cases.

PMID- 11307484
TI  - [Avoidable "fever of unknown origin" due to Ralstonia pickettii bacteremia].
AB  - Ralstonia pickettii bacteraemia from the atrial part of a ventriculo-atrial shunt
      was diagnosed as the cause of recurring febrile episodes with systemic toxicity
      in a 38-year old female. A prior neurosurgical resection of intracerebral
      cavernoma was complicated by postoperative recurrent meningitis with this non
      fermenting gram-negative rod, due to an intra-operative contamination of a in
      situ shunt, from which only the intracerebral part of the ventriculo-atriostomy
      had been removed, following the episodes of meningitis. Ralstonia pickettii is a
      rare isolate and is seldom identified as a human pathogen. It formerly belonged
      to the genera Pseudomonas and Burkholderia. There are some casuistic reports of
      nosocomial bacteraemias, associated with the use of contaminated IV products or
      aerosols. There was an important diagnostic delay due to (1) insufficient
      communication between the different medical doctors in several hospitals, in
      different episodes of the clinical follow-up and (2) a misinterpretation of a
      positive blood culture with R. pickettii, which was interpreted as contamination.
      This misinterpretation and insufficient data transfer caused a considerable delay
      in the diagnostic process.

PMID- 11307485
TI  - Anorexia nervosa complicated by pancytopenia and sepsis.

PMID- 11307486
TI  - [Oral anticoagulation in older patients. Establishment and validation of a new
      posologic warfarin regimen].
AB  - OBJECTIVE: Warfarin is highly effective in preventing thromboembolism and more
      recent clinical trials have established that adjusted dosing is highly effective
      in reducing the risk of ischemic stroke in patients with nonvalvular atrial
      fibrillation. Fear of major hemorrhage frequently dissuades physicians from use
      of anticoagulants in older people. In addition, the time needed to reach the
      therapeutic range may be excessively long and delicate in this population.
      PATIENTS AND METHODS: This study was undertaken in two phases. In the first
      phase, 20 patients (mean age 84 years) were given 5 mg of warfarin once daily for
      3 consecutive days. During the following days, the dose of warfarin was adjusted
      to reach an International Normalized Ratio (INR) in the therapeutic range
      (between 2 and 3). The good correlation (r = -0.77, p < 0.01) between the INR on
      day 4 and the daily maintenance dose was used to establish an algorithm to
      predict the maintenance dose of warfarin. In the second phase, this algorithm was
      successfully tested in 94 elderly patients, mean age 84 years (range 74-99).
      RESULTS: The predicted dose on day 4 was effective in 56% within +/- 0.5 mg and
      in 92% within +/- 1 mg of the original predicted dose. No hemorrhagic
      complication occurred during the study. The therapeutic range was reached on day
      4 in 63.5% and on day 1 in 91% of the patients. CONCLUSION: We have developed a
      method of predicting the maintenance dose of warfarin in a very old population
      based on the INR. This method is safe and easy to use.

PMID- 11307487
TI  - [Gastrointestinal functional disorders. National evaluation survey of patient
      symptoms and management].
AB  - OBJECTIVE: An anonymous self-administered questionnaire was completed by patients
      with gastrointestinal functional disorders to determine symptoms and management
      strategies employed. METHODS: The questionnaire was filled out by 1266 patients
      who complained of abdominal pain in 8 out of 10 cases as well as disturbed bowel
      movements and abdominal distension. RESULTS: Half of the patients had started
      self medication, generally before consulting their general practitioner. The
      patients were generally satisfied with their medical care. Superior efficacy was
      observed for antispasmodics in combination or not with anxiolytic agents (75%,
      71% and 69% efficacy respectively). The digestive disorders led to an
      interruption of occupational activities in 21% of the patients. DISCUSSION:
      Optimal management of patients with this benign chronic disorder that
      nevertheless has a major impact on their quality of life requires sufficient
      knowledge of the opinions of both the patients and their physicians. A second
      survey on this question has been initiated.

PMID- 11307488
TI  - [Highly elevated alphafetoprotein and hepatic cirrhosis. It is not always
      hepatocarcinoma].
AB  - BACKGROUND: Alphafetoprotein assay contributes considerably to the diagnosis of
      hepatocarcinoma in patients with hepatic cirrhosis. We report the case of a
      cirrhotic patient whose elevated alphafetoprotein level was not associated with
      liver disease. CASE REPORT: Alphafetoprotein level was followed in a 64-year-old
      man with hepatic cirrhosis. A rise from 415 to 7690 ng/ml between June and
      November 1997 led to the discovery of adenocarcinoma of the cardia with liver
      metastasis. This extrahepatic adenocarcinoma was probably the cause of
      inappropriate secretion of alphafetoprotein. DISCUSSION: Primary liver tumors are
      obviously not the only source of elevated alphafetoprotein levels. High levels
      can also be observed in certain, notably digestive tract and embryonary, cancers.
      Gastric hepatoid adenocarcinoma is a recently described histological entity first
      described in 1970. Typically, there is an inappropriate secretion of
      alphafetoprotein due to a secondary liver tumor.

PMID- 11307489
TI  - [Domestic malaria in Nice (France) probably transmitted via the airport].

PMID- 11307490
TI  - [Treatment of acute malaria with quinine in a non-immunized patient: rationale
      for a 7-day regimen].

PMID- 11307491
TI  - [Pleural sarcoidosis: contribution of thoracoscopy].

PMID- 11307492
TI  - [Short-term psychotherapy and "standard" care in depressed patients in general
      medicine].

PMID- 11307493
TI  - [History of continuing medical education in the United States].
AB  - Continuing medical education came into being in the United States in the late
      twenties when the mediocrity of the initial medical training of practicing
      physicians was recognized. Medical schools created a classical system of
      continuing education; the first mandatory program was initiated in urology in
      1934. By 1957, the first set of guidelines for good medical practice were
      published by the American Medical Association (AMA). The mandatory nature of
      continuing education was widespread by the end of the sixties with variable
      regulations from state to state. At the same time, the AMA created an honorary
      diploma for physicians who complete 150 h post-graduate training within 3 years.
      Starting in 1970, the political predominance of the AMA in continuing education
      was questioned by other professional associations (hospitals, medical schools).
      After much discussion and opposing debate, a common association for continuing
      education was created in 1981. The AMA remained a leader in the early nineties
      and now has started programs targeted to patients.

PMID- 11307495
TI  - [Epidemiology of tinea capitis].
AB  - PREDOMINANT IN CHILDREN: Tinea capitis is the most frequent fungal infection in
      children under the age of puberty. It occurs only rarely in men but is observed
      in adult women. Human-to-human, animal-to-human and soil-to-human transmission
      can be involved. HISTORICAL BACKGROUND: The spectrum of fungal species known to
      cause tinea capitis has steadily grown for more than a century, varying with the
      local urban or rural environment. Since the beginning of the 20th century and up
      to the advent of griseofulvin in the sixties, M. audouinii, an anthropophilic
      species, caused major epidemics in France, England and the USA. In the sixties to
      eighties, M. canis was the cause of most cases observed throughout the world.
      Over the last 20 years, anthropophilic species have again become the leading
      cause of tinea capitis epidemics, particularly in large cities, in relationship
      with immigration: T. tonsuransi in the USA and England and T. soudanense and M.
      langeronii in France. HYGIENE AND EDUCATION: Despite the benign curable nature of
      the disease, interhuman transmission of tinea capitis is nevertheless a
      considerable public health problem due to the increasing number of children
      affected and the risk of contagion in schools. The considerations resulting from
      recent studies point out the fact that transmission occurs more often in the
      family than the school setting, particularly indirectly by common use of grooming
      instruments. This would explain the high percentage of tinea capitis in large
      immigrant families where hair combing habits favor transmission. In France, these
      observations should lead to a revision of the current regulations concerning
      expulsion from school of children affected by tinea capitis. Better education
      would be a more appropriate response to the problem.

PMID- 11307496
TI  - [Arachidonic acid and prostaglandins, inflammation and oncology].
AB  - CYCLOOXYGENASE PATHWAY: Among the 3 metabolic pathways leading to oxidation of
      arachidonic acid, the cyclooxygenase (COX) pathway produces prostaglandin G2 that
      is rapidly transformed into prostaglandin H2. PROSTAGLANDINS: Prostaglandins are
      inflammation mediators that are strongly implicated in tumorgenesis. They
      participate in tumor initiation, promotion and growth. INFLAMMATION AND
      EPITHELIAL CANCER: Chronic inflammation is a risk factor for epithelial cancer.
      It induces prostaglandin synthesis via activation of COX-2. There is a cause and
      effect relationship between chronic inflammation and carcinogeneis via COX-2
      expression. It has been demonstrated that COX-2 favors tumor invasion and
      inhibits apoptosis. Tumor growth is favored by PGE2-induced reduction in
      immunity; COX-2 inhibitors reinforce the immune response. Finally COX-2 is
      expressed in tumor neovessels and plays a role in angiogenesis.

PMID- 11307494
TI  - [Treatment of arthritis in the elderly: how should paracetamol be prescribed?].

PMID- 11307497
TI  - [Cyclooxygenases].
AB  - TWO ISOFORMS: There are two isoforms of cyclooxygenase (COX) with similar
      structure and metabolic activity. COX-1 is a constitutional enzyme. COX-2 is an
      inductible form. CYCLOOXYGENASE-1: COX-1 is present in most tissues, particularly
      in the kidney, the digestive tract mucosa, platelets, brain, liver and spleen.
      CYCLOOXYGENASE-2: COX-2 expression can be induced by an inflammatory process.
      Implicated in the development of certain cancers, COX-2 is expressed in numerous
      tumor cell lines and in most epithelial carcinomas. COX-2 favors tumor invasion
      and inhibits apoptosis. When it is absent, tumor growth is slower or stopped.

PMID- 11307499
TI  - [To sum up. Who we are and where we are going].

PMID- 11307500
TI  - [The electric revolution that changed the world. Two centuries ago Volta
      presented the pile].

PMID- 11307498
TI  - [Cyclooxygenase inhibitors].
AB  - DISTINCT EFFECTS: Since the discovery of the two isoforms of COX, the therapeutic
      effects of nonsteroidal antiinflammatory drugs (NSAID) can be distinguished from
      their adverse effects linked to the inhibition of the constitutional form via
      selective inhibition of the inducible form. Non-selective NSAID that inhibit both
      COX isoforms are difficult to use for long-term regimens. NSAID AND CANCER
      PREVENTION: Epidemiology studies and animal and in vitro studies have
      demonstrated that regular use of NSAID reduced the incidence of colorectal cancer
      and certain precancer lesions. PROMISING PERSPECTIVES: COX-2 specific inhibitors,
      for example cerecoxib or rofecoxib, are potentially interesting for human therapy
      for chemoprevention of epithelial cancer or as medical treatment, alone or in
      combination with other anticancer treatments.

PMID- 11307501
TI  - [Beta-thalassemia. History began also in Ferrara].

PMID- 11307503
TI  - [Diagnostic imaging of bone metastases].
AB  - PURPOSE: To present an "algorithm" for detection and diagnosis of skeletal
      metastases, which may be applied differently in symptomatic and asymptomatic
      cancer patients. MATERIAL AND METHODS: February to March 1999 we randomly
      selected and retrospectively reviewed the clinical charts of 100 cancer patients
      (70 women and 30 men; mean age: 63 years, range: 55-87). All the patients had
      been staged according to TNM criteria and had undergone conventional radiography
      and bone scan; when findings were equivocal, CT and MRI had been performed too.
      RESULTS: The primary lesions responsible for bone metastases were sited in the:
      breast (51 cases), colon (30 cases: 17 men and 13 women), lung (7 cases: 6 men
      and 1 woman), stomach (4 cases: 2 men and 2 women), skin (4 cases: 3 men and 1
      woman), kidney (2 men), pleura (1 woman), and finally liver (1 men). The most
      frequent radiographic pattern was the lytic type (52%), followed by
      osteosclerotic, mixed, lytic vs. mixed and osteosclerotic vs lytic patterns. The
      patients were divided into two groups: group A patients were asymptomatic and
      group B patients had local symptoms and/or pain. DISCUSSION: Skeletal metastases
      are the most common malignant bone tumors: the spine and the pelvis are the most
      frequent sites of metastasis, because of the presence of high amounts of red
      (hematopoietic active) bone marrow. Pain is the main symptom, even though many
      bone metastases are asymptomatic. Pathological fractures are the most severe
      consequences. With the algorithm for detection and diagnosis of skeletal
      metastases two different diagnostic courses are available for asymptomatic and
      symptomatic patients. Bone scintigraphy remains the technique of choice in
      asymptomatic patients in whom skeletal metastases are suspected. However this
      technique, though very sensitive, is poorly specific, and thus a negative bone
      scan finding is double-checked with another physical examination: if the findings
      remain negative, the diagnostic workup is over. On the contrary, in patients with
      a positive bone scan or with local symptoms and pain, radiography and CT are used
      for screening of metastatic lesions: results may be negative (for low sensitivity
      of conventional radiology) or questionable (in which case bone biopsy is
      necessary), or else symptoms may be due to different causes than metastatic
      lesions (i.e., osteoarthritis). Before bone biopsy is made, MRI must be
      performed, because it is the only technique that allows to distinguish between
      bone marrow components. The limitation of MRI is the poor specificity of its
      findings, which may provide misleading findings.

PMID- 11307502
TI  - [3D spiral computerized tomography in the reconstructive treatment of malignant
      maxillofacial tumors].
AB  - PURPOSE: To investigate the role of Helical CT and the usefulness of three
      dimensional (3D) imaging for preoperative planning and follow-up of
      reconstructive maxillofacial surgery with alloplastic material in neoplastic
      disease involving this region. MATERIAL AND METHODS: From 1996 to 1999 eleven
      patients were examined with Helical CT and 3D images for planning of
      maxillofacial plastic and reconstructive surgery for advanced cancer of this
      anatomically complex region. A 3D-modulated titanium mesh (100%) or micronets was
      used to rebuild the anterior surface of maxillary bone and the orbital floor. The
      mesh was cut to the appropriate size and shape and curved where necessary. Within
      the residual sinusal cavity a siliconed filling was used surmounting an acrylic
      prosthesis with dental arch to rebuild the palate. A rehydrated bovine
      pericardium was affixed and moduled on the borders in two cases only. Three
      dimensionally reconstructed CT images were obtained preoperatively and at least 6
      months postoperatively in all patients. The images were generated on a computer
      workstation using the shaded surface display (SSD) software with threshold values
      ranging 425 to 630 HU, and a more closed window for the imaging of titanium
      mesh/bone interface in the postsurgical follow-up. RESULTS: We always obtained an
      excellent complete spatial depiction of maxillofacial region both before and
      after surgery, with no artefacts so important as to affect the 3D reconstruction
      process and the image quality. Together with the head-neck surgical team we could
      work for preoperative planning through CT scans by different 3D points of view.
      The 3D reconstructed follow-up scans showed good filling of the defect in the
      area where the titanium mesh had been used. Then efficacious bone modelling and
      good biocompatibility of the alloplastic material were seen in all patients, with
      no inflammatory reactions. CONCLUSIONS: Titanium is a well-known material, which
      is widely used for cranioplasty. It is a radiolucent, nonferrous metal of low
      atomic number that allows very clear CT and MR images to be obtained. Further Ti
      features are strength, biocompatibility and easy handling. 3D Helical CT scan has
      proved to be the most complete and accurate imaging technique for reconstructive
      plastic surgery with alloplastic material in advanced maxillofacial cancer, also
      considering the anatomic and functional complexity of this area. The prospect is
      provided to identify virtual 3D presurgical ablation planes. These may allow the
      surgeon to improve plastic reconstruction and shorten intervention time.

PMID- 11307504
TI  - [Diagnostic imaging of lobular carcinoma of the breast: mammographic,
      ultrasonographic and MR findings].
AB  - PURPOSE: To evaluate the most frequent mammographic, US and MR findings of
      invasive lobular carcinoma and the role of MRI in defining multifocality and/or
      multicentricity of this tumor histotype. MATERIAL AND METHODS: We studied 45
      lobular carcinomas (39 patients) were selected from 421 breast cancers. Core
      biopsy with a 14 G needle was performed in 39 cases, under US guidance in 36/39
      and under mammographic guidance in 3/39 cases. Surgical biopsy was performed in 2
      cases and the diagnosis could be made only after mastectomy in 5 cases. All
      patients were examined with mammography and US and (10-13 MHz) and 8 also with
      MRI. RESULTS: 28/46 palpable lesions (60.9%). Core biopsy correctly diagnosed
      38/39 lesions (97.4%). The most frequent mammographic findings was that of a
      nodular opacity without microcalcifications (34.8%), followed by a mass with
      spiculated borders (30.4%). Microcalcifications were seen in one case only
      (2.2%). Mammography detected no abnormalities in 15.2% of cases, but US showed a
      lesion in 2 of these cases. The most frequent US pattern was that of a hypoechoic
      lesion (43.5%), followed by posterior US beam attenuation. No US signs of
      abnormality were seen 15.2%. MRI correctly detected 13 lesions. Contrast
      enhancement was greater than 70% at one minute in 10 cases and greater than 40%
      in one case; two lesions exhibited atypical slow contrast enhancement, peaking at
      5 minutes. MRI detected 5 lesions missed at both mammography and US and showed
      multifocal (3 and 2) lesions where the other techniques had detected one lesion
      only. DISCUSSION: At mammography and US invasive lobular carcinoma exhibits no
      different features than ductal carcinoma but is difficult to identify especially
      in its early stages. US is a useful tool especially to characterize mammography
      detected lesions but in our experience it also demonstrated 2 lesions missed at
      mammography. MRI is a precious examination to define the multifocal, multicentric
      or bilateral character of invasive lobular carcinoma. CONCLUSIONS: Invasive
      lobular carcinoma of the breast is often very difficult to diagnose. Thus, we
      suggest the use of integrated diagnostic imaging with mammography, US and, in
      some cases, MRI for earlier diagnosis and to identify further tumor
      localizations.

PMID- 11307505
TI  - [Computerized tomography in the study of thoracic-pulmonary complications after
      liver transplantation].
AB  - PURPOSE: To review the role of Computed Tomography (CT) in thoracic complications
      following orthotopic liver transplantation (OLT). MATERIAL AND METHODS: In a post
      OLT population of 567 patients transplanted in our institution, 100 patients
      (17.6%) were examined with chest CT. We reviewed data relative to the total
      number of examinations, clinical and/or radiographic indications, the CT
      technique--i.e., conventional (with(out) intravenous, i.v., contrast material) or
      high-resolution (HRCT). We also reviewed the radiologic patterns and their
      correlation with the other clinical, bronchoscopic and/or laboratory results.
      RESULTS: Of 152 chest CT examinations, 45 (29.6%) were performed because of
      clinical indications, 31 (20.4%) because of a radiographic abnormality, 64
      (42.1%) because of clinical and radiographic indications, while in 12 cases
      (7.9%) the reasons were unknown; 133/152 (87.5%) examinations had been performed
      with conventional CT scanning (100 with i.v. contrast agent and 33 without) and
      19/152 (12.5%) with HRCT. Twenty of 152 (13.2%) examinations, in 16 patients,
      were normal; in the other 84 patients, 132/152 (86.8%) CT/HRCT studies showed 247
      pathological findings (99 pleural effusions, 3 pericardial effusions, 62 cases of
      atelectasis, 1 pulmonary calcification, 70 suspected inflammatory parenchymal
      consolidations, 64 of them alveolar and 6 interstitial, 4 cases of interstitial
      edema and finally 8 neoplastic infiltrates). DISCUSSION: Correlated with clinical
      data, CT findings are very useful in detailing clinical-radiographic screening
      findings, despite the limitations in typifying pleural effusions, in
      differentiating atelectases from inflammatory parenchymal consolidations and in
      assessing pneumonia etiology. Also, despite its high sensitivity (94.1%) and
      specificity (92.8%), CT was not accurate enough in the differential diagnosis of
      pneumonia. History data were necessary to characterize the histology of
      neoplastic infiltrates. CONCLUSIONS: Chest CT has relatively uncommon, and
      sometimes only clinical, indications in post-OLT patients. The technique is
      chosen based on clinical-radiographic findings. CT proved useful in showing
      negative cases and in detailing clinical and radiographic findings but must be
      integrated with clinical findings to define inflammatory and neoplastic
      conditions.

PMID- 11307506
TI  - [Evaluation of hemodynamic significance of arteriovenous coronary fistulas:
      diagnostic integration of coronary angiography and stress/rest myocardial
      scintigraphy].
AB  - PURPOSE: We report on the importance of the integration of data obtained from
      digital coronary angiography and stress/rest 99mTc sestamibi myocardial perfusion
      single photon emission tomography in evaluating the hemodynamic significance of
      coronary arteriovenous fistulae. MATERIAL AND METHODS: Coronary fistulae were
      detected with coronary angiography in 9 patients. All patients underwent clinical
      examination, transthoracic echocardiography, stress electrocardiogram and
      stress/rest 99mTc sestamibi myocardial perfusion single photon emission
      tomography. RESULTS: Stress/rest 99mTc sestamibi myocardial perfusion single
      photon emission tomography and stress electrocardiogram showed stress-induced
      myocardial ischemia in 2 patients. The first patient with familial predisposition
      and risk factors for ischemic heart disease presented a mesocardic heart murmur
      on clinical examination. At stress ECG (125 Watt, 153 b/m' max frequency 93%,
      arterial pressure 230 mmHg, max frequency pressure product 35,200) ischemic
      alterations were recorded at the first minute of the second stage of the Bruce
      protocol. Coronary angiography detected a circumflex artery fistula in the
      coronary sinus. Stress/rest 99mTc sestamibi myocardial perfusion single photon
      emission tomography for the evaluation of stress/rest perfusion detected a
      reversible perfusion defect of the proximal portion of the posterolateral and
      lateral walls, thus confirming the hemodynamic importance of the flow through the
      fistula during stress cycloergometric testing. In the second patient familial
      predisposition to ischemic heart disease and previous inferior wall myocardial
      infarction and non-significant stress ECG, coronary angiography identified a
      subocclusive stenosis of the right coronary artery and an anomaly between the
      anterior interventricular artery and the left pulmonary artery. The presence of
      the contrast medium in the left pulmonary artery identified a flow from the left
      ventricle to the left pulmonary artery. Good angiographic results were obtained
      after percutaneous coronary angiography of the right coronary artery stenosis.
      Due to the onset of angina stress/rest 99mTc sestamibi myocardial perfusion
      single photon emission tomography was performed to evaluate stress/rest perfusion
      (75 Watt, 125 b/m', 88% max frequency, arterial pressure 200 mmHg, double max
      product 25,000 with ST depression of 1.5 mm in V1-V4) and identified an
      irreversible perfusion defect due to infarction and a reversible perfusion defect
      of the anterior wall and apex due to ischemia caused by the anomalous flow
      through the coronary fistula. The correspondence between the site of the coronary
      artery where the fistula originates, identified by coronary angiography, and the
      reversible perfusion defects, identified by stress/rest 99mTc sestamibi
      myocardial perfusion single photon emission tomography, indicates that the
      anomalous flow through the fistula may cause myocardial ischemia. The
      irreversible perfusion defects of the inferior wall are the result of right
      coronary artery subocclusive stenosis. CONCLUSIONS: Coronary fistulae cause
      myocardial ischemia only in a small number of patients. Data obtained from single
      photon emission tomography in evaluating stress/rest myocardial perfusion,
      correlated with data from coronary angiography, have shown that changes in
      patients with terminal coronary anomalies may be due to different coronary
      diseases: ischemia to anomalous flow through the fistula and myocardial
      infarction to subocclusive right coronary artery stenosis. Stress/rest 99mTc
      sestamibi single photon emission tomography for the evaluation of myocardial
      perfusion is a reliable means of assessing the functional importance of the
      terminal coronary anomalies detected by coronary angiography. Evaluation of the
      hemodynamic importance of the coronary fistulae is indispensable in programming
      corrective surgery.

PMID- 11307507
TI  - [Optimization of the technique of virtual colonoscopy using a multislice spiral
      computerized tomography].
AB  - PURPOSE: To optimize scanning parameters for virtual colonoscopy utilizing a
      multislice Helical CT scanner in an in vitro study (using a homemade colonic
      phantom) and in a preliminary clinical study. MATERIAL AND METHODS: A colonic
      phantom was built using a plastic tube and 12 plastiline polyps were placed
      inside. The colonic phantom was studied with a multislice Helical CT scanner.
      Axial images were obtained with the phantom parallel to the long axis of the
      moving table (in order to simulate the evaluation of ascending and descending
      colon): oblique images were acquired with the phantom at 45 degrees relative to
      the long axis of the moving table (in order to simulate the evaluation of sigmoid
      colon and colonic flexures). Four different scanning protocols were tested: 1)
      slice collimation, 5 mm; slice width, 7 mm; table speed, 25 mm; reconstruction
      index, 5 mm; 2) slice collimation, 2.5 mm; slice width, 3 mm; table speed, 15 mm;
      reconstruction index, 3 mm; 3) slice collimation, 1 mm; slice width, 1.25 mm;
      table speed, 5 mm; reconstruction index, 1 mm; 4) slice collimation, 1 mm; slice
      width, 1.25 mm; table speed, 4 mm; reconstruction index, 1 mm. Quantitative
      analysis consisted in evaluation of the number of identified polyps and polyp
      size along the longitudinal axis. Qualitative analysis consisted in the
      evaluation of image artifacts and quality of 3D reconstructed images (step
      artifacts and polyp geometry distortion). This preliminary clinical study was
      performed in 12 patients (7 men and 5 women) who underwent multislice Helical CT
      colonography. We selected patients with clinical indications for conventional
      colonoscopy or after unsuccessful conventional colonoscopy. RESULTS: Multislice
      Helical CT colonography was 100% sensitive in the detection of all polyps and in
      all scanning protocols. With oblique scans, only a 3-mm polyp was missed during
      protocol 1 (sensitivity: 92%). Polyp geometry distortion was observed on
      longitudinal reconstructions, whereas no distortion was seen on axial images.
      Image quality was graded as optimal for protocols 2, 3, and 4; protocol 1 was
      graded as good on transverse scans and as poor on oblique scans. In our
      preliminary clinical study, two colonic carcinomas and three polyps were
      identified. CONCLUSIONS: At present, the introduction of multislice technology in
      virtual colonoscopy permits to improve spatial resolution and image definition.
      The actual clinical advantage, in terms of increased diagnostic accuracy, needs
      further investigation in larger clinical studies.

PMID- 11307508
TI  - [Liver trauma due to penetrating lesions: miscellanea, personal case series,
      clinical and CT findings].
AB  - PURPOSE: Penetrating liver wounds are related to many causes and rank second
      after blunt abdominal and liver trauma. We will report the clinical and
      radiological findings of our personal series of patients with penetrating trauma,
      especially by firearms and stab and cut wounds. We will also try to define the
      diagnostic workup of these traumas, which is especially based on CT signs of
      liver damage and associated changes and which is of basic importance for
      following treatment, both surgical or conservative. MATERIAL AND METHODS: In the
      last seven years we retrospectively reviewed 31 cases of penetrating liver
      trauma. The patients were 19 men and 12 women, ranging in age 18 to 73 (mean 42),
      with penetrating liver injuries from firearms (16 patients) and stab (9 cases)
      wounds; 6 patients had injuries from different causes. Abdominal CT was carried
      out in emergency with the CT Angiography (CTA) technique in all patients. In the
      patients with suspected chest and abdomen involvement CT was performed from the
      mid-chest for accurate assessment of diaphragm and lung bases and to exclude
      associated pleuropulmonary damage. RESULTS: Penetrating liver wounds were caused
      by firearms in 70% of cases, by stabbing in 12% and, in the extant 18%, by other
      causes such as home accidents, road and work traumas, and liver biopsy. In our
      series, the liver was most frequently involved, especially by firearms wounds; in
      our 16 cases the most frequent injuries were hemorrhagic tears. We found bullets
      in the liver in 6 cases. In one case of home accident the patient wounded himself
      while slicing bread with a long knife, which cut into the anterior abdominal wall
      and tore the anterior liver capsule, as seen at CTA. DISCUSSION AND CONCLUSIONS:
      Penetrating wounds to liver and abdomen are less frequent than those to the
      chest. In the past decade the use of CT has changed the diagnostic and
      therapeutic approach to such injuries completely, decreasing the resort to
      explorative laparotomy and hepatorrhaphy. Indeed, CT provides a clear picture of
      the extent and severity of damage, which permits to choose a conservative
      treatment in case of intraparenchymal hematomas and lacerocontusive foci without
      hemoperitoneum, which can be followed-up with physical and CT examinations.
      Moreover, Helical CT could provide the early diagnosis of active bleeding in the
      peritoneum and of focal bleeding in the liver, thus permitting prompt
      hepatorrhaphy or targeted hepatectomy. A diaphragm injury suspected at CT should
      always prompt the surgeon to intervention, especially when hemothorax, lung base
      pneumothorax, large liver hematoma or tear of the liver dome are associated.
      Finally, subdiaphragmatic free gas indicates gut perforation associated with
      liver damage, in which case surgery is necessary too.

PMID- 11307509
TI  - [Diffusion weighted MR: principles and clinical use in selected brain diseases].
AB  - PURPOSE: To define the principles and technical bases of diffusion weighted MR
      imaging of the brain and report our experience in the evaluation of selected
      brain disorders including age-related ischemic white matter changes
      (leukoaraiosis), neoplastic and infective cysts and wallerian degeneration.
      MATERIAL AND METHODS: Between May 1999 and June 2000 we examined seventeen
      patients: 10 patients with leukoaraiosis and deterioration of cognitive and motor
      function, 5 patients with focal cystic lesions (one anaplastic astrocytoma, one
      glioblastoma, one metastasis from squamous cell lung carcinoma, one pyogenic
      abscess and one case with cerebral tubercolosis) and 2 patients with wallerian
      degeneration (one with post-hemorrhagic degeneration of right corticospinal tract
      and one with post-traumatic degeneration of left optic tract). All patients
      underwent a standard cranial MR examination including SE T1-, proton density, T2
      weighted, FLAIR and diffusion weighted images. Post-contrast T1-weighted
      sequences were also obtained in the patients with cystic lesions. Diffusion
      weighted images were acquired with double shot echoplanar sequences. Diffusion
      sensitizing gradient along the x, y and z axes and b values ranging 800 to 1200
      s/mm2 were used. For each slice a set of three orthogonal diffusion "anisotropic"
      images, an "isotropic" image and a standard T2-weighted image were reconstructed.
      Postprocessing included generation of the apparent diffusion coefficient maps and
      of the "trace" image that reflects pixel by pixel the diffusional properties of
      water particles only. Values of mean diffusivity within regions of interest were
      computed in the "trace" image and compared with those obtained in contralateral
      brain areas. In patients with leukoaraiosis the diffusivity in posterior
      periventricular white matter was compared with that measured in 10 age-matched
      control subjects without leukoaraiosis. RESULTS: In patients with leukoaraiosis
      the areas of increased periventricular signal intensity on T2-weighted images
      showed a significantly higher (p < 0.001) diffusivity (mean values 124.7 +/- 21.3
      x 10(-5) mm2/s) as compared to control subjects (mean values 85 +/- 7 x 10(-5)
      mm2/s). Diffusion weighted images in 2 patients revealed the presence of a small
      focal area of increased signal and reduced diffusivity in "trace" images
      consistent with recent ischemic lesion. In neoplastic cystic lesions the central
      necrotic/cystic content was always hypointense on diffusion weighted images and
      showed increased diffusivity on "trace" images. On the other hand the central
      necrotic content of the pyogenic brain abscess was hyperintense and showed low
      diffusivity. In patients with wallerian degeneration diffusion weighted images
      and "trace" images demonstrated loss of anisotropy and increased diffusivity in
      the affected white matter tract relative to the contralateral. DISCUSSION: The
      increased diffusivity observed in areas of leukoaraiosis and the identification
      of subclinical acute ischemic lesions by diffusion weighted images might be more
      useful than standard MR sequences for monitoring the disease progression.
      Diffusion weighted images allow differentiation of the different parts of focal
      cystic lesions (edema, solid and cystic/necrotic portion) and are useful to
      differentiate pyogenic brain abscess from necrotic tumors. In patients with
      wallerian degeneration the loss of anisotropy and the increase of diffusivity
      values in the affected tract are probably related to myelin breakdown and allow
      better recognition of the affected tract relative to standard MR images.
      CONCLUSIONS: Diffusion weighted MR imaging can be performed during a standard
      cranial MR examination and add useful clinical information in several brain
      disorders besides acute ischemic stroke.

PMID- 11307510
TI  - [Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach.
      Clinical results].
AB  - PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric
      approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or
      uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189
      patients with biochemically confirmed hyperthyroidism and performed thyroid
      ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43
      patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in
      89 patients. In 28 patients we found cold thyroid nodules and performed fine
      needle aspiration with negative cytology for thyroid malignancy in all cases.
      Antithyroid drugs were stopped 5 days till radioiodine administration and, if
      necessary, restored 15 days after the treatment. Radioiodine uptake test was
      performed in all patients and therapeutic activity calculated to obtain a minimal
      activity of 185 MBq in the thyroid 24 hours after administration. The minimal
      activity was adjusted based on clinical, biochemical and imaging data to obtain a
      maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical
      tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was
      started when hypothyroidism occurred. In Graves' disease patients a mean activity
      of 370 MBq (distribution 259-555 MBq) was administered. Three months after
      treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%)
      patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%)
      hyperthyroid. Three of the latter were immediately submitted to a new radioiodine
      administration while 32 hypothyroid patients received thyroxine treatment. One
      year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43
      (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni-
      and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555
      MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were
      euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately
      submitted to a new radioiodine administration. One year posttreatment 142 of 146
      (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels
      above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS:
      The simplified dosimetric method illustrated in our paper is very effective in
      clinical practice because it permits to avoid resorting to sophisticated but also
      imprecise quantitative methods. Hypothyroidism should not be considered as a
      major collateral effect of radioiodine treatment, particularly in Graves'
      disease. In fact, the pathogenesis of the disease requires an ablative treatment
      with both surgery and radioidine treatment and the control of hyperthyroidism and
      the prevention of relapse are the major clinical targets. Vice versa,
      hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our
      dosimetric approach was applied.

PMID- 11307511
TI  - [Patient radiation protection: the radiologist's duties and responsibility
      according to Italian law D.Lgs 187/00 and Euratom law 97/43].

PMID- 11307512
TI  - [The reducing lens: usefulness of a simple instrument in thoracic radiology].

PMID- 11307513
TI  - [Medals of radiology].

PMID- 11307514
TI  - [A case of condensing osteitis of the clavicle].

PMID- 11307516
TI  - [Pediatric use of thoracic high-resolution CT in the diagnosis of idiopathic
      pulmonary fibrosis. A case report].

PMID- 11307515
TI  - [A rare case of cystic ameloblastoma with multiple recurrences: diagnostic
      imaging].

PMID- 11307517
TI  - [A rare complication caused by prosthetic mesh in inguinal hernioplasty. A case
      report].

PMID- 11307519
TI  - [Necrotizing fasciitis of the scrotum (Fournier's gangrene): ultrasound
      findings].

PMID- 11307518
TI  - [Wide neoplastic perforation of diverticular colon. Report of a case studied with
      computerized tomography].

PMID- 11307520
TI  - [Current role of computerized tomography in the diagnosis and follow-up of
      Castleman's disease. Evaluating 2 mixed-variety cases].

PMID- 11307521
TI  - [Solitary cerebral metastasis of endometrial carcinoma. A case report].

PMID- 11307522
TI  - [Primary choriocarcinoma of the mediastinum with paraneoplastic syndromes. A case
      report].

PMID- 11307523
TI  - [Rarely its is really spontaneous....].

PMID- 11307524
TI  - [Reflux esophagitis].

PMID- 11307525
TI  - [Helicobacter-related gastric and duodenal lesions].

PMID- 11307526
TI  - [Inflammatory intestinal diseases].

PMID- 11307527
TI  - [Colonic adenoma and precancerous condition].

PMID- 11307528
TI  - [Chronic viral liver dysfunction].

PMID- 11307529
TI  - [Increasing incidence of type C hepatic cancer: current status of diagnosis and
      treatment].

PMID- 11307530
TI  - [Physiopathology, diagnosis, and treatment of cholelithiasis--with special
      reference to hepato-intestinal circulation of bile acid].

PMID- 11307531
TI  - [Physiopathology and treatment of severe acute pancreatitis].

PMID- 11307532
TI  - [Progress in the study of physiopathology, diagnosis, and treatment of digestive
      system diseases].

PMID- 11307533
TI  - [Treatment of peptic ulcer in the age of Helicobacter pylori].

PMID- 11307534
TI  - [Diagnosis and treatment of early colonic cancer].

PMID- 11307535
TI  - [From viral hepatitis to hepatocellular carcinoma].

PMID- 11307536
TI  - [Headache--recent progress in diagnosis and treatment].

PMID- 11307537
TI  - [Physiopathology and treatment of neuropathies--recent progress].

PMID- 11307538
TI  - [Diabetes mellitus--current topics].

PMID- 11307539
TI  - [Diagnosis, treatment, and exacerbating factors of thyroid diseases].

PMID- 11307540
TI  - [Systemic lupus erythematosus--current concept and treatment].

PMID- 11307541
TI  - [Diagnosis and non-surgical treatment of chronic rheumatoid arthritis].

PMID- 11307542
TI  - [Current status of hypertension therapy--application of evidence-based medicine].

PMID- 11307543
TI  - [Physiopathology and the current status of treatment of chronic heart failure-
      application of evidence-based medicine].

PMID- 11307544
TI  - [New strategy for the management of interstitial pneumonia].

PMID- 11307545
TI  - [Physiopathology and treatment of bronchial asthma].

PMID- 11307546
TI  - [Diagnosis and treatment of chronic leukemia].

PMID- 11307547
TI  - [Clinical application of hematopoietic factors].

PMID- 11307548
TI  - [Physiopathology and treatment of progressive kidney diseases].

PMID- 11307549
TI  - [Current status of HIV infection].

PMID- 11307550
TI  - Wanted--universal guidelines.

PMID- 11307551
TI  - Human histologic and histomorphometric analysis comparing OsteoGraf/N with PepGen
      P-15 in the maxillary sinus elevation procedure: a case report.
AB  - The use of the anorganic bovine bone mineral OsteoGraf/N combined with
      demineralized freeze-dried bone allograft has received widespread use in sinus
      elevations. This composite graft material has proven to be suitable, predictable,
      and successful for the placement and integration of endosseous implants in the
      edentulous, atrophic maxilla. In this case study, the current materials and
      accepted methodology were compared with the latest tissue-engineered bone
      replacement graft material, PepGen P-15. PepGen P-15 is a combination of
      OsteoGraf/N and a synthetic peptide (P-15) that mimics the cell-binding domain of
      Type-I collagen responsible for cell migration, differentiation, and
      proliferation. The radiographic, histologic, and histomorphometric evaluations of
      the sinus grafted with PepGen P-15 showed enhanced bone formation within a
      shorter time interval compared with the composite graft material of OsteoGraf/N
      and demineralized freeze-dried bone allograft.

PMID- 11307552
TI  - Histomorphometric evaluation of titanium implants in osteoporotic rabbits.
AB  - In this study, the osteointegration of two kinds of titanium implants were
      analyzed (cylindrical and screw-type) inserted in the tibiae of control (n = 8)
      and osteoporotic (n = 12) female rabbits. Osteoporosis was induced by the
      surgical removal of the ovaries (oophorectomy). Bone mass density of all animals
      was evaluated by densitometry of the tibiae and vertebrae. Densitometry was
      carried out at the beginning of the study and 4 months after oophorectomy. Mass
      loss in the tibia was not observed, however, in the vertebrae there was an 11%
      loss compared with the initial value. The implants remained for 8 weeks, after
      which the animals were then sacrificed and bone segments were analyzed by
      histomorphometry. The trabecular volume and mineral apposition rate was
      significantly greater in control animals than in osteoporotic animals,
      independent of which type of implant was used. In the osteoporotic animals, the
      area and osteoid perimeter were greater than in the control animals. By measuring
      the thickness of the compact layer in the tibia, it was observed that in the
      control animals, it was 28% thicker than in the osteoporotic animals. This study
      leads to the conclusion that bone formation was greater in the control animals
      than in the osteoporotic animals. The screw-type implants yielded the greatest
      formation of bone both in the control and in the osteoporotic animals.

PMID- 11307553
TI  - Effect of varying fixture width on stress and strain distribution associated with
      an implant stack system.
AB  - The purpose of this investigation was to evaluate the dissipation of a force
      applied to an assembled stack of implant components. The stack consisted of a 10
      mm threaded implant, a screw-retained abutment and a screw-retained gold crown.
      The dissipation of force was analyzed in relation to varying the implant diameter
      with and without a concomitant change in abutment diameter. Two experimental
      groups were evaluated. The first group consisted of 25 titanium screw-form
      implants (Implant Innovations, Inc.). These implants measured 10 mm in length and
      3.25 mm, 3.75 mm, 4.0 mm, 5.0 mm, and 6.0 mm in diameter. The second group
      included 15 titanium screw-form implants (Nobel Biocare, Inc.) measuring 10 mm in
      length and 3.75 mm, 4.0 mm, and 5.0 mm in diameter. All implants were embedded in
      standardized photoelastic resin blocks. Points of interest were marked on each
      block using standardized templates to ensure consistency. Implants were restored
      using system-specific conical abutments and standardized single-unit
      restorations. A strain gauge was affixed to each abutment, and an eccentric load
      of 176 N was applied to the restoration. Periimplant stresses were measured using
      photoelastic analysis. Abutment strain was determined using an electronic strain
      indicator. Data were collated and compared using ANOVA and the Duncan multiple
      range statistical tests. When stress was analyzed at points on the resin-implant
      interface or a fixed distance from the interface, stress tended to decrease from
      the 5-mm-wide implant to the 6-mm-wide implant. Stress in relation to the 3.25
      mm, 3.75-mm, and 4.0-mm implant was not as well defined, indicating the
      possibility that some deformation of implants was occurring. Increased abutment
      width resulted in decreased abutment strain. Therefore, using a wider abutment
      may be helpful in preventing preload reduction in clinical applications. This may
      reduce the incidence of loosening and fracture of abutment and restoration
      screws.

PMID- 11307554
TI  - Histometric evaluation of bone regeneration around immediate implants partially
      in contact with bone: a pilot study in dogs.
AB  - Bone regeneration was evaluated around immediate implants partially in contact
      with bone, with or without the concurrent application of a combination of
      platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-1).
      Mandibular premolars were removed, and the implant osteotomies were prepared; a
      uniform circumferential gap was prepared 1.25 mm beyond the width of the implant
      bed in the coronal half. Twelve implants (8.5 x 3.75 mm) were inserted in six
      dogs. Before insertion, an implant received a single application of 5
      micrograms/mL of PDGF and IGF-1 delivered in 0.10 mL of 4% methylcellulose gel or
      0.10 mL of 4% methylcellulose gel only as a control. To label regenerated bone, a
      2% calcein green solution was administered by intramuscular injection at 0, 7,
      15, 30, and 45 days after implant insertion Three and 8 weeks after implant
      insertion undecalcified sections were obtained, and the degree of bone to implant
      contact, the bone area, and the intensity of bone labeling were measured into the
      limits of the eight most coronal threads of the implant (four threads on each
      side of each implant). The results showed a greater extension of bone-to-implant
      contact, a larger percentage of bone area, and greater intensity of bone labeling
      for test versus control implants (P < .01). Within the limits of the present
      study, it was concluded that the combination of PDGF/IGF-1 might be an
      alternative for enhancing bone healing around implants partially in contact with
      bone.

PMID- 11307555
TI  - Retrospective multicenter study of an anodized, tapered, diminishing thread
      implant: success rate at exposure.
AB  - Performance of a new tapered, threaded implant at exposure was evaluated
      retrospectively using conservative assessment criteria. The criteria used were
      intended to ensure that an implant in the early stages of failing as well as
      those implants that have clearly failed would be identified as such. These
      results reflect an evaluation preliminary to comparing the performance of the
      implant at exposure and its performance (i.e., success rate) observed after
      longer periods (i.e., > or = 1 year) of loaded service. Data from 663 patients
      treated in the setting of the authors' private practice offices were evaluated to
      assess the performance of the implant under representative "clinical practice"
      usage conditions. The implant success/failure criteria were prospectively defined
      and applied to data obtained in a masked fashion from patients' records. Neither
      the dentist nor personnel involved in the analysis of the data were aware of
      which patients were qualified for and included into the study. Of 1100 implants
      available for evaluation, 15 implants failed at or before exposure. The success
      rate at exposure was 98.6%. There was no correlation between the anatomical
      region in which an implant was placed and the incidence of implant failure.
      Implants placed in fresh extraction sites and/or grafted sites appeared to be
      more likely to fail at exposure. Conversely, the failure rate of implants placed
      using a single-stage surgical procedure was comparable to that of implants placed
      using a conventional two-stage surgical methodology. Immediately loaded implants
      experienced a success rate comparable to that of implants placed using
      conventional two-stage surgical procedures. Factors under the clinician's control
      may play a substantial role in determining implant performance at exposure.

PMID- 11307556
TI  - Evaluation of the inferior alveolar canal by cross-sectional hypocycloidal
      tomography.
AB  - The aim of this study was to evaluate the possibility of locating the inferior
      alveolar canal (IAC) before mandibular posterior osteotomy or implant surgery
      using a computer-controlled hypocycloidal tomographic system. A 1-mm-thick cross
      section and a 6-mm-thick sagittal tomographic layer were made either through the
      proposed implant sites or through the center of the mandibular posterior teeth in
      55 patients. The system used was a CommCAT IS 2000 tomographic unit in a
      hypocycloidal motion. The visibility of the location of the IAC was graded as
      excellent, good, fair, or invisible. In total, 119 sites were assessed. The
      visibility of the IAC was graded as excellent or good in 74% and fair in 11.7% of
      the sites. In 14.3% of cases, the canal was graded as invisible. Conventional
      hypocycloidal tomography has been shown to be a useful radiographic technique for
      preoperative assessment of the IAC in the posterior mandible.

PMID- 11307557
TI  - Retrievable cement-retained implant-tooth-supported prosthesis: a new technique.
AB  - Clinicians often encounter difficulties with connecting natural teeth and
      osseointegrated implants. A new clinical technique with laboratory procedures are
      presented. The technique involves cementation of a two-part prosthesis over
      natural teeth and customized implant gold cylinders. This method achieved a
      passive-fit fixed bridge with retrievability maintained.

PMID- 11307558
TI  - Immediate loading of titanium hexed screw-type implants in the edentulous
      patient: case report.
AB  - Histologic and histomorphometric studies in both animals and humans have shown
      that more rapid and greater bone-to-implant contact can be achieved with implants
      that incorporate certain surface characteristics compared with the original
      machined-surface implants. Such findings are significant because various implant
      designs may allow the fixtures to sufficiently resist functional loading sooner
      than originally thought. The case report presented here indicates that immediate
      loading of hexed titanium screw-type implants in the anterior mandible can lead
      to successful osseointegration and clinical outcome. The number of implants
      placed, their distribution, and the type of rigid connection are critical
      considerations for immediate loading. A bone height that can accommodate dental
      implants > or = 10 mm long is recommended. Biomechanically, the implants to be
      immediately loaded must be stable and resistant to macromovement to ensure good
      osseointegration.

PMID- 11307559
TI  - Use of a titanium papillary insert for the construction of interimplant papillae.
AB  - Constructing the interimplant papilla is important to achieve an optimally
      esthetic implant-supported restoration. To obtain support for the soft tissue
      between two implants so as to result in the desired interdental papilla-like
      shape, a papillary titanium insert was fabricated. It eliminates the need for any
      bone grafting procedures with less armamentarium and a reduction of the number of
      surgical entries. This article describes the papillary titanium insert and
      focuses on its advantages, manipulations, and handling.

PMID- 11307560
TI  - A new sinus lift technique in conjunction with placement of 265 implants: a 6
      year retrospective study.
AB  - A new surgical crestal approach for implant placement in deficient alveolar
      ridges is presented. Drills of different and increasing lengths allow the surgeon
      to approach the membrane without risk of tearing it. The study is supported by
      265 cases and a 6-year follow-up period (1994-1999). Implants that were 13 and 15
      mm in length were inserted, respectively, in 205 and 60 cases. The alveolar ridge
      height varied between 4 and 10 mm. All implants were HA-coated and had a 3.25-mm
      diameter. The results of this investigation suggest that this is a reliable and
      predictable technique for the prosthetic rehabilitation of the maxillary
      posterior regions in the presence of anatomical restrictions for implant
      placement.

PMID- 11307562
TI  - The relationship between cigarette smoking and dental implant failure.
AB  - This paper examines the effect of tobacco use on the failure rates of dental
      implants. A review of 56 dental implant patients with a total of 187 endosseous
      dental implants, placed over a four year period, demonstrated a significant
      association between increased implant failure rates and cigarette smoking with
      failure rates of 16.6% in smokers compared to 6.9% in non-smokers. Also implant
      length was shown to be a significant factor with shorter implants (< or = 10 mm)
      being more susceptible to failure in smokers. A chi-square test was used for data
      analysis. Current recommendations that should be given to implant patients who
      smoke are included.

PMID- 11307561
TI  - Implant-supported overdenture therapy: a 3- to 8-year prospective study.
AB  - Inflammatory changes in periimplant soft tissues and loss of alveolar bone can
      develop as in periodontal diseases. This clinical phenomena has been described as
      periimplantitis. Microorganisms such as Gram-negative anaerobic rods,
      spirochetes, and bacteroides that are seen in subgingival flora in periodontitis
      have also been found in sulcular microflora in periimplantitis. The purpose of
      this study was to evaluate periimplant tissue changes in totally edentulous
      patients who had implant-supported overdentures for 3 to 8 years (5-5.5 years)
      clinically from both a subjective and an objective point of view. The clinical
      parameters used in this study can be helpful in the evaluation of periimplant
      tissue health.

PMID- 11307563
TI  - In vitro repair of all-ceramic and fibre-reinforced composite crowns.
AB  - Shear bond strength between fibre reinforced composite and all-ceramic frameworks
      and veneering/repair composites was investigated after different surface
      treatments for evaluating the possibility of a repair. Then, 24 crowns were
      adhesively luted on human teeth and artificially aged. Repair quality was
      characterized by a loading to fracture test, where undamaged crowns were compared
      to repaired crowns. To simulate repeated damage, aging and repair, the procedure
      was performed three times for each crown. A combined silicate-silane treatment of
      the fibre-reinforced composite frameworks and the hydrofluoric acid etching of
      the ceramic showed good repair qualities and a sufficient fracture strength for
      clinical application.

PMID- 11307564
TI  - Control of jaw closing forces: a comparison between natural tooth and
      osseointegrated implant.
AB  - The aim of this in vivo study was to compare the precision of control of jaw
      closing forces through implants versus natural teeth. Ten partially dentate
      subjects with fixed implant prostheses in their mandibles took part in the study.
      A force transducer was used to assess the ability of the subjects to follow pre
      determined jaw closing cycles. The error in tracking the target increased as the
      force increased for both implant and tooth sites. Within the range of forces
      tested, there was no significant difference in the error between the implant and
      natural tooth sites.

PMID- 11307565
TI  - Long-term results of telescopic crown retained dentures--a retrospective study.
AB  - The clinical data for 250 telescopic crown retained dentures involving 617
      abutment teeth preparations were collected and analysed in a retrospective study
      to ascertain the survival rate of the dentures and their abutment teeth. During
      the study period 10.6% of the abutment teeth had to be extracted. An increased
      number of telescopic crowns significantly improved the longevity of the
      prostheses and their associated abutment teeth in most denture designs, but this
      was not found to be the case with bilateral free-end saddle designs without an
      anterior bounded saddle. The use of more than four abutment teeth did not result
      in a higher survival rate.

PMID- 11307566
TI  - A literature review of the techniques to measure tooth wear and erosion.
AB  - This paper reviews methods to measure tooth wear especially those more recently
      introduced as a result of improvements in technology. The review searched methods
      to measure tooth wear and dental erosion from large epidemiological
      investigations, in vitro and in vivo studies. There seems to be wide variation in
      techniques used to measure tooth wear and erosion. In vitro techniques may have
      little direct clinical relevance but can lead to new and more accurate clinical
      methods. In vivo studies have problems with reference points and accurate
      validation of the techniques. There is a need for a simple, reliable technique to
      quantify tooth wear due to erosion.

PMID- 11307567
TI  - Patient knowledge concerning their referral to a restorative dental unit in a
      community clinic: a pilot study.
AB  - One hundred patients referred to a Community Dental Service completed a
      questionnaire, the purpose of which was to find out why they perceived they had
      been referred and to whom they thought they had been referred. The results showed
      that most patients (64) perceived they would see a Specialist rather than a
      Consultant and most (63) thought they had been referred because their dentist
      could not treat their problem. There was no significant relationship between age
      and to whom the patient thought they had been referred, and further analysis to
      estimate the effect of age, gender and length of time with the current dentist or
      the reasons for referral failed to show any significant relationships.

PMID- 11307568
TI  - Empirical investigation and conceptual development.

PMID- 11307569
TI  - "Managing" the poor: neoliberalism, Medicaid HMOs and the triumph of consumerism
      among the poor.
AB  - In order to explore the contradictions of neoliberal health policy, this article
      examines Medicaid managed care in Philadelphia. At the federal and state levels,
      government is increasingly promoting private-sector market-based strategies over
      policies formerly associated with the welfare state, arguing that the former are
      the most effective means of achieving economic growth and guaranteeing social
      welfare. A prime example of this shift, Medicaid managed care is a policy by
      which states contract with private-sector health maintenance organizations to
      provide health coverage to the poor. Drawing on ethnographic and historical data,
      this paper shows how Pennsylvania's Medicaid managed care program has created
      access barriers for poor Philadelphians. It also illustrates how ideologies that
      justify this policy shift serve to mask its detrimental effects on the poor. By
      contrasting the state's consumerist model with one group's protest efforts, this
      article calls into question the neoliberal ideology that undergirds health and
      welfare "reform."

PMID- 11307570
TI  - Sociocultural change and health status among the Seri Indians of Sonora, Mexico.
AB  - The influence of changes in sociocultural status on obesity, arterial blood
      pressure, and depression was examined in a cohort of 81 Seri Indians living in
      two communities in Sonora, Mexico. Residents of the less acculturated and
      modernized community, Desemboque, exhibited significantly higher waist
      circumference and prevalence of obesity than did residents of the more
      acculturated and modernized community of Punta Chueca. The prevalence of obesity
      was also significantly associated with low levels of acculturation and
      modernization, while the prevalence of clinically significant depressive symptoms
      was associated with low levels of modernization and household income. Lifestyle
      incongruity was a significant independent risk factor for body mass index and
      depressive symptom scores but not for arterial blood pressure. The results
      support the notion of a curvilinear relationship between health status and
      sociocultural change in which health status initially declines with increasing
      lifestyle incongruity but eventually improves with increasing acculturation,
      modernization, and income.

PMID- 11307571
TI  - Risk, uncertainty, and agency: culture and safe motherhood in Morocco.
AB  - This article critically examines the notion that Moroccan women's infrequent use
      of health facilities during pregnancy and birth results from their lack of
      awareness of the risks of childbirth. It argues that while ethnographic data
      appear at first to lend support to this hypothesis, a closer examination of the
      customs surrounding birth shows that ideas about risk are found in local
      constructions of childbirth. The choices women make regarding birth and the
      flexibility that characterizes their decisions reflect the uncertain
      circumstances of labor and problems in the accessibility and quality of health
      services. Differences in the notions of risk that women hold and express are a
      function, not of an inability to conceive of risks, but rather of the real
      alternatives they have for controlling these risks.

PMID- 11307572
TI  - Executive Summary of the Health Care Productivity Report.
AB  - Governments and health care organizations are increasingly interested in ways to
      rethink and reform their health care systems. To help provide a foundation for
      future reform, the authors examined the health care systems in the United States,
      Germany, and the United Kingdom. The authors assessed productivity in the
      treatment of four diseases during the late 1980s: diabetes, cholelithiasis
      (gallstones), breast cancer, and lung cancer. The authors looked at the different
      day-to-day actions of doctors and hospitals and tried to connect these actions to
      differences in longevity and the quality of life.

PMID- 11307573
TI  - Assessing the impact of payment method and practice setting on German physicians'
      practice patterns.
AB  - This project determined the impact that a physician's practice setting and
      reimbursement method has on his or her practice behavior. Multivariate
      regressions that controlled for physician, patient, and practice characteristics
      were conducted. The primary data source was a questionnaire that sampled
      ambulatory physicians practicing in the state of Brandenburg, Germany. This
      research demonstrated that physicians paid on a fee-for-service basis differ
      significantly from practitioners paid a salary in captured utilization measures:
      more patient visits per week, including more follow-up visits; a decreased rate
      of hospitalization; and an increased likelihood of making house calls. A group
      practice setting demonstrated little impact when compared with a solo practice.

PMID- 11307574
TI  - How Israeli primary care physicians perceive their role in the health care
      system.
AB  - In some Western European countries, primary care physicians (PCPs) play a major
      role in the health care system, but in Israel the health care system is in the
      process of being reformed and the role of PCPs has not yet been established. The
      purpose of the study described in this article was to determine the attitude of
      PCPs toward the role that they should play in the health care system in Israel
      and the formal training they need to fill this role. PCPs cited 12 primary
      functions that they should carry out, including coordinating patient care and
      counseling patients. Also, 60% of PCPs have undergone specialty training, and 94%
      think that this training is essential. Among the conclusions of the study are
      that a higher percentage of PCPs should undergo specialty training in order to
      enhance their professional status and that continued medical education should
      emphasize specific issues, such as the consideration of economic factors in
      patient management decisions, responsibility for patients' administrative issues,
      24-hour responsibility for patients, and house calls.

PMID- 11307575
TI  - Quality improvement in primary care and the importance of patient perceptions.
AB  - Increasing consumerism poses many challenges for health care providers,
      particularly for those in primary care. Quality improvement to meet patients'
      heightened demand for service excellence will require effective, continuous
      measurement of patient perceptions. The study described in this article evaluated
      the psychometric properties of a new instrument designed to survey patients'
      experiences with the delivery of primary care and assessed the factors that
      contribute to patient retention and likelihood to return. By systematically
      measuring patient satisfaction and perceptions of quality, medical practices can
      increase the effectiveness of primary care, improve patient outcomes, and control
      costs.

PMID- 11307576
TI  - Conducting clinical trials in a constantly changing health care environment.
AB  - Continuous change and cost containment characterize the current health care
      system, making conduct of clinical trials and other clinical research difficult.
      Identification, accrual, and follow-up of patients who move between health care
      environments such as hospitals, nursing homes, schools and the home is
      particularly challenging. This article describes a circuit rider approach to
      patient identification and follow-up that was established by the Communication
      Sciences and Disorders Clinical Trials Research Group. It also gives suggestions
      for design of clinical trials in a constantly changing environment.

PMID- 11307577
TI  - Health claims data as a strategy and tool in disease management.
AB  - A comprehensive definition of disease management provides an opportunity to track
      a population of patients across the entire continuum of a condition, from
      wellness through disease and disability, so that improvements in health status
      and quality of life and efficiencies in the application of health care resources
      can be demonstrated. The need is great for information systems that can
      computerize clinical encounter, summarize, and apply the information to help
      identify opportunities for improvement in the performance of quality and cost
      control, monitor processes of care, and report outcomes that are meaningful to
      the organization. By tracking health care charges as a proxy for the application
      of health care resources, health claim data analyses can identify conditions for
      disease management, facilitate provider buy-in, develop the disease management
      program, monitor interventions, and report outcomes.

PMID- 11307579
TI  - The leverage of the law: the increasing influence of law on healthcare ethics
      committees.

PMID- 11307580
TI  - Healthcare ethics committees and the law: uneasy but inevitable bedfellows.

PMID- 11307581
TI  - Persistent legislative state: law, education, and the well-intentioned healthcare
      ethics committee.

PMID- 11307582
TI  - The reach of ethics into the law.

PMID- 11307583
TI  - Maryland's ethics committee legislation--a leading edge model or a step into the
      abyss?

PMID- 11307584
TI  - The Texas Advance Directives Act of 1999: politics and reality.

PMID- 11307585
TI  - Ethics committees under Texas law: effects of the Texas Advance Directives Act.

PMID- 11307586
TI  - The spectrum of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.
      Clinical experience based on 22 patients from 18 Spanish families.
AB  - The enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) catalyzes the
      reutilization of hypoxanthine and guanine to the purine nucleotides IMP and GMP,
      respectively. HPRT deficiency is an X-linked disorder characterized by uric acid
      overproduction and variable neurologic impairment. The complete deficiency of
      HPRT is diagnostic of Lesch-Nyhan syndrome manifested by choreoathetosis,
      spasticity, mental retardation, and self-injurious behavior. In some HPRT
      deficient patients the enzyme defect appeared to be "partial" and the neurologic
      symptoms mild to severe (Kelley-Seegmiller syndrome). This has prompted the
      classification of HPRT deficiency in 2 distinct groups: Lesch-Nyhan syndrome and
      Kelley-Seegmiller syndrome, which has created much confusion. A spectrum of
      clinical consequences of HPRT deficiency has been recognized in small series of
      patients, but the complete spectrum of the neurologic disorder has not been
      described in a single series of patients examined by the same observers. We
      analyzed our experience with 22 patients belonging to 18 different families with
      HPRT deficiency diagnosed at "La Paz" University Hospital in Madrid over the past
      16 years. The clinical spectrum of these HPRT-deficient Spanish patients was
      similar to the different phenotypes occasionally reported in the literature, in
      some cases diagnosed as Lesch-Nyhan "variants." The clinical, biochemical,
      enzymatic, and molecular genetic studies on these 22 patients allowed us to
      delineate a new classification of HPRT deficiency. Based on the neurologic
      symptoms, dependency for personal care, HPRT activity in hemolysate and in intact
      erythrocytes, and predicted protein size, patients were classified into 4 groups:
      Group 1 (2 patients), normal development with no neurologic symptoms, HPRT
      activity was detectable in hemolysates and in intact erythrocytes, and the
      mutation did not affect the predicted protein size. Group 2 (3 patients) mild
      neurologic symptoms that did not prevent independent lives, HPRT activity was
      detectable in intact erythrocytes, and the protein size was normal. Group 3 (2
      patients), severe neurologic impairment that precluded an independent life, no
      residual HPRT activity, and normal protein size. Group 4 (15 patients), clinical
      characteristics of Lesch-Nyhan syndrome (some may not show self-injurious
      behavior), no residual HPRT activity, and in most (7 of 8 patients in whom the
      mutation could be detected) the mutation affected the predicted protein size.
      This classification of HPRT deficiency into 4 groups may be more useful in terms
      of accuracy, reproducibility, assessment for treatment trials and prognosis. The
      study of this Spanish series allows us to conclude that HPRT deficiency may be
      manifested by a wide spectrum of neurologic symptoms; the overall severity of the
      disease is associated with mutations permitting some degree of residual enzyme
      activity; and mutation analysis provides a valuable tool for prognosis, carrier
      identification, and prenatal diagnosis.

PMID- 11307587
TI  - Enterobacter sakazakii infections among neonates, infants, children, and adults.
      Case reports and a review of the literature.
AB  - Enterobacter sakazakii can cause serious infections especially among the very
      young and the elderly. It continues to be more common among neonates and infants
      than adults. Its tropism for the central nervous system in neonates and infants
      remains a mystery. Among neonates and infants, E. sakazakii has a propensity to
      cause meningitis resulting in ventriculitis, brain abscess or cyst formation, and
      development of hydrocephalus requiring ventricular-peritoneal shunt. Computed
      tomography of the head is therefore useful in following patients with E.
      sakazakii meningitis. Mortality and morbidity of E. sakazakii meningitis is high,
      and virtually all patients recovering from the central nervous system infection
      suffered mental and physical developmental delays. The case-fatality rate
      decreased among patients with meningitis treated with the third-generation
      cephalosporins. Most adults with E. sakazakii infection had serious underlying
      diseases and 50% of the adults with the infection had malignancies. However there
      has never been a known case of meningitis. Increasing antibiotic resistance among
      Enterobacter species should lead one to consider using the carbapenems or the
      newer cephalosporins in combination with a second agent such as an
      aminoglycoside. Limited data suggest that trimethoprim-sulfamethoxazole may be a
      useful agent in the treatment of infections caused by the Enterobacter species,
      especially in view of the production of extended-spectrum beta-lactamases capable
      of inactivating the cephalosporins and extended-spectrum penicillin.

PMID- 11307589
TI  - Commercial tattooing as a potentially important source of hepatitis C infection.
      Clinical epidemiology of 626 consecutive patients unaware of their hepatitis C
      serologic status.
AB  - Tattooing in commercial tattoo parlors is known to transmit blood-borne viral
      infections, including hepatitis C virus (HCV), in other countries, but its
      contribution to the high population prevalence of HCV infection in the United
      States has been incompletely evaluated. Risk factors for blood-borne infection
      were assessed by physician's interview of 626 consecutive patients undergoing
      medical evaluation for spinal problems in 1991 and 1992 while unaware of their
      HCV status. Later all were screened for HCV infection with enzyme-linked
      immunosorbent assay (EIA-1 and EIA-2), and positives were confirmed with second
      generation recombinant immunoblot assay (RIBA). Forty-three patients were
      seropositive for HCV (sample prevalence 6.9%, population-standardized prevalence
      2.8%). Logistic regression analysis identified 4 independent risk factors for HCV
      infection: injection-drug use (adjusted prevalence odds ratio [OR] = 23.0; 95%
      confidence intervals [CI] = 7.5-70.6), ancillary hospital jobs held by men (OR =
      9.6; 95% CI = 3.8-24.3), tattoos from commercial tattoo parlors (OR = 6.5; 95% CI
      = 2.9-14.8), and drinking > or = 3 6-packs of beer per month (OR = 4.0; 95% CI =
      1.8-8.7). If causal, these 4 risk factors account for 91% of HCV infections, with
      tattooing explaining 41%, heavy beer drinking 23%, injection-drug use 17%, and
      ancillary health care jobs for men 8%. Transfusions, promiscuous sexual activity,
      bone grafts, acupuncture, perinatal or intimate transmission in families, and
      other modes were not independently associated with serologic evidence of HCV
      infection. Unlikely to be explained by confounding or incomplete disclosure of
      other risk factors, tattooing in commercial tattoo parlors may have been
      responsible for more HCV infections than injection-drug use.

PMID- 11307588
TI  - Infections in patients with immunodeficiency with thymoma (Good syndrome). Report
      of 5 cases and review of the literature.
AB  - Immunodeficiency with thymoma (Good syndrome, GS) is a rare, adult-onset
      condition that is characterized by thymoma, hypogammaglobulinemia, and low
      numbers of peripheral B cells. CD4+ T lymphopenia and an inverted CD4:CD8+ T-cell
      ratio may be present. Here we report 5 patients with GS and infectious
      complications who were seen at 3 institutions between 1983 and 1999. Three
      patients had recurrent sinopulmonary infections, 3 had severe cytomegalovirus
      (CMV) disease, and 1 had Pneumocystis carinii pneumonia. Review of the literature
      identified 46 other reports of infections in GS patients. The infections reported
      in all 51 patients included recurrent sinopulmonary infection (19 cases with
      documented respiratory pathogens), generally with encapsulated bacteria, most
      often Haemophilus influenzae (11 cases); CMV disease (5 cases); bacteremia (7
      cases); oral or esophageal candidiasis (6 cases); persistent mucocutaneous
      candidiasis (5 cases); chronic diarrhea (5 cases with documented stool
      pathogens); urinary tract infections (4 cases); P. carinii pneumonia (3 cases);
      tuberculosis (2 cases); Kaposi sarcoma (1 case); disseminated varicella (1 case);
      candidemia (1 case); wound infection with Clostridium perfringens (1 case);
      Mycoplasma arthritis (1 case); and other infections. Patients with GS present
      with a spectrum of sinopulmonary infections and pathogens similar to common
      variable immunodeficiency (CVID). Compared with patients with CVID, opportunistic
      infections, including severe CMV disease, P. carinii pneumonia, and mucocutaneous
      candidiasis, appear to be more common in patients with GS, and patients with GS
      may have a worse prognosis. GS should be ruled out in patients with thymoma or
      CVID who develop severe, especially opportunistic, infections. Treatment with
      intravenous immune globulin is recommended for all patients with GS.

PMID- 11307590
TI  - Community-acquired pneumonia. A prospective outpatient study.
AB  - We initiated a prospective study with a group of practitioners to assess the
      etiology, clinical presentation, and outcome of community-acquired pneumonia in
      patients diagnosed in the outpatient setting. All patients with signs and
      symptoms suggestive of pneumonia and an infiltrate on chest X-ray underwent an
      extensive standard workup and were followed over 4 weeks. Over a 4-year period,
      184 patients were eligible, of whom 170 (age range, 15-96 yr; median, 43 yr) were
      included and analyzed. In 78 (46%), no etiologic agent could be demonstrated. In
      the remaining 92 patients, 107 etiologic agents were implicated: 43 were due to
      "pyogenic" bacteria (39 Streptococcus pneumoniae, 3 Haemophilus spp., 1
      Streptococcus spp.), 39 were due to "atypical" bacteria (24 Mycoplasma
      pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella spp.), and
      25 were due to viruses (20 influenza viruses and 5 other respiratory viruses).
      There were only a few statistically significant clinical differences between the
      different etiologic categories (higher age and comorbidities in viral or in
      episodes of undetermined etiology, higher neutrophil counts in "pyogenic"
      episodes, more frequent bilateral and interstitial infiltrates in viral
      episodes). There were 2 deaths, both in patients with advanced age (83 and 86
      years old), and several comorbidities. Only 14 patients (8.2%) required
      hospitalization. In 6 patients (3.4%), the pneumonia episode uncovered a local
      neoplasia. This study shows that most cases of community-acquired pneumonia have
      a favorable outcome and can be successfully managed in an outpatient setting.
      Moreover, in the absence of rapid and reliable clinical or laboratory tests to
      establish a definite etiologic diagnosis at presentation, the spectrum of the
      etiologic agents suggest that initial antibiotic therapy should cover both S.
      pneumoniae and atypical bacteria, as well as possible influenza viruses during
      the epidemic season.

PMID- 11307591
TI  - Extracolonic manifestations of Clostridium difficile infections. Presentation of
      2 cases and review of the literature.
AB  - Clostridium difficile is most commonly associated with colonic infection. It may,
      however, also cause disease in a variety of other organ systems. Small bowel
      involvement is often associated with previous surgical procedures on the small
      intestine and is associated with a significant mortality rate (4 of 7 patients).
      When associated with bacteremia, the infection is, as expected, frequently
      polymicrobial in association with usual colonic flora. The mortality rate among
      patients with C. difficile bacteremia is 2 of 10 reported patients. Visceral
      abscess formation involves mainly the spleen, with 1 reported case of pancreatic
      abscess formation. Frequently these abscesses are only recognized weeks to months
      after the onset of diarrhea or other colonic symptoms. C. difficile-related
      reactive arthritis is frequently polyarticular in nature and is not related to
      the patient's underlying HLA-B27 status. Fever is not universally present. The
      most commonly involved joints are the knee and wrist (involved in 18 of 36
      cases). Reactive arthritis begins an average of 11.3 days after the onset of
      diarrhea and is a prolonged illness, taking an average of 68 days to resolve.
      Other entities, such as cellulitis, necrotizing fasciitis, osteomyelitis, and
      prosthetic device infections, can also occur. Localized skin and bone infections
      frequently follow traumatic injury, implying the implantation of either
      environmental or the patient's own C. difficile spores with the subsequent
      development of clinical infection. It is noteworthy that except for cases
      involving the small intestine and reactive arthritis, most of the cases of
      extracolonic C. difficile disease do not appear to be strongly related to
      previous antibiotic exposure. The reason for this is unclear. We hope that
      clinicians will become more aware of these extracolonic manifestations of
      infection, so that they may be recognized and treated promptly and appropriately.
      Such early diagnosis may also serve to prevent extensive and perhaps unnecessary
      patient evaluations, thus improving resource utilization and shortening length of
      hospital stay.

PMID- 11307592
TI  - Penicillium marneffei: types and drug susceptibility.
AB  - The PCR fingerprints of 30 Penicillium marneffei isolates from Chiang Rai in
      Northern Thailand and Bangkok in central Thailand were studied through use of
      single-nucleotide primers (GACA)4 and the phage M13 core sequence. Discrimination
      of fingerprint patterns was based on differences in the number of major bands.
      The P. marneffei isolates were divided into four types, i.e., A, B, C, and D.
      Type A was found in two isolates from Chiang Rai (6.7%). Types B and C
      respectively were found in two (6.7%) and one (3.3%) isolates from Bangkok. The
      predominate type D (83.3%) was found in isolates obtained from Chiang Rai and
      Bangkok. The PCR fingerprinting method was found to be useful for the
      epidemiological study of P. marneffei, a dimorphic opportunistic fungus and an
      emerging pathogen in the HIV pandemic. In vitro drug susceptibility testing by
      broth macrodilution to four antifungal agents against the yeast form of P.
      marneffei was performed. The MIC ranges for amphotericin B, fluconazole,
      itraconazole, and ketoconazole were 0.125-0.5, 4.0-8.0, < 0.032, and < 0.125
      microgram/ml respectively.

PMID- 11307593
TI  - Electrophoretic karyotyping and antifungal susceptibility patterns of Candida
      parapsilosis clinical isolates causing deep and superficial fungal infections.
AB  - Forty-six isolates of Candida parapsilosis, each from a single patient, were
      collected from July 1993 through March 1999 at the University of Ancona Hospitals
      and Clinics. Twenty-eight strains were isolated from superficial lesioned sites,
      including skin, nails and other sources while 18 strains were isolated from
      blood. The isolates were typed by electrophoretic karyotyping (EK) and tested for
      their susceptibility to fluconazole (FLC), itraconazole (ITC), flucytosine (5
      FC), and amphotericin B (AMB). Our data confirmed that EK is a useful technique
      for DNA typing of isolates of Candida parapsilosis and showed that the source of
      isolation is not associated with a given DNA type. Although strains belonging to
      this species of Candida are susceptible to the most common antifungals, including
      the triazoles, the degree of ITC susceptibility was dose dependent (MIC ranging
      from 0.25-0.5 microgram/ml) for 98% of the isolates.

PMID- 11307594
TI  - Respiratory syndrome very similar to extrinsic allergic alveolitis due to
      Penicillium verrucosum in workers in a cheese factory.
AB  - A respiratory syndrome very similar to extrinsic allergic alveolitis due to
      Penicillium verrucosum was recognized in 4 workers employed in a Gorgonzola
      cheese factory. A mycogen allergy to P. verrucosum, used as starter in the
      production, was demonstrated by positive sputum culture and detection of specific
      antibodies in the blood. Intense and prolonged exposure to inhalation of fungal
      spores could have lead to the development of this allergic response. The fact
      that 2 of the subjects are siblings seems to indicate host susceptibility or
      immunological constitution in the pathogenesis of the respiratory allergy.

PMID- 11307595
TI  - Extracellular enzymatic activity of Malassezia spp. isolates.
AB  - Extracellular enzymatic activity of different species of Malassezia spp was
      evaluated. Thirty-three isolates of animal origin (dogs and cats) and stock
      culture samples were studied. Twenty isolates of M. pachydermatis, 8 of M.
      furfur, 2 of M. sympodialis and M. globosa and one of M. restricta, M. obtusa and
      M. slooffiae were examined. The enzymatic activity was investigated using Api Zym
      system. The enzymatic patterns showed light differences. Esterase lipase,
      Phosphatase acid and Naphtol-AS-BI-phosphohydrolase were produced in significant
      amounts from most isolates excepted for M. restricta, confirming the limited
      enzymatic activity of this species. Data obtained from the other new species
      described after the revision of the genus, appear to be quite homogeneous.
      Dixon's broth appeared to be a valid medium for the growth of all Malassezia spp.

PMID- 11307596
TI  - Muscular-skeletal cryptococcosis in a patient with idiopathic CD4+ lymphopenia.
AB  - A healthy 27-year-old woman presented, four months after childbirth, ingravescent
      pain and claudication of the left lower limb. Magnetic Resonance Imaging of the
      lumbosacral and iliac regions showed widespread muscular-skeletal lesions. The
      patient underwent surgery; Cryptococcus neoformans was isolated from surgical
      samples. Liposomal amphotericin B, fluconazole and itraconazole were
      administered. Laboratory findings showed lymphocytopenia, with reduction of CD4+
      lymphocytes (23 cells per cubic millimeter) in the absence of HIV infection and
      any other defined immunodeficiency. This is a rare case of muscular-skeletal
      cryptococcal infection isolated in a subject affected with idiopathic CD4+
      lymphocytopenia.

PMID- 11307597
TI  - Systemic Candida infection in University hospital 1997-1999: the distribution of
      Candida biotypes and antifungal susceptibility patterns.
AB  - A total of 102 Candida species were isolated from blood cultures from January
      1997 to October 1999. Using assimilation of carbohydrate test, 52 (51.0%) of the
      Candida sp. were identified as C. parapsilosis, 25.5% (26) were C. tropicalis. C.
      albicans made up 11.8% (12), 6.9% (7) were C. rugosa, 3.8% (4) C. glabrata and 1%
      (1) C. guilliermondii. No C. dubliniensis was found in the study. In vitro
      antifungal susceptibility tests showed that all Candida species were sensitive to
      nystatin, amphotericin B and ketoconazole. Although all isolates remained
      sensitive to fluconazole, intermediate susceptibility was found in 3 C. rugosa
      isolates. Antifungal agents with high frequency of resistance were econazole,
      clotrimazole, miconazole and 5-fluorocytosine. Candida species found to have
      resistance to these antifungal agents were non-C. albicans.

PMID- 11307598
TI  - Tinea cruris epidemiology (Sao Paulo, Brazil).
AB  - In order to determine the epidemiology of tinea cruris in Sao Paulo, Brazil, an
      investigation was carried out from April 95 to March 1997. A total of 2000
      individuals were studied, of whom 105 were suspected of having tinea cruris
      infection. Direct microscopy and/or culture were positive in 66 [62.8%] of the
      cases. Erythematous-scale plaques and erythematous-liquenificated plaques were
      the most frequently found clinical types. T. rubrum was the prevalent
      dermatophyte in 90% of the cases, followed by T. tonsurans (6%) and T.
      mentagrophytes (4%).

PMID- 11307599
TI  - Incidence of seed-borne fungi and aflatoxins in Sudanese lentil seeds.
AB  - Thirteen seed samples of lentil (Lens esculenta) were incubated on agar plate and
      moist filter papers (Moist Chambers) at 28 +/- 2 degrees C for determination of
      the incidence of seed-borne fungi. Aflatoxins content of the seeds was measured
      using the bright greenish- yellow fluorescence test (BGYF) and thin-layer
      chromatography (TLC). Sixty-nine species and seven varieties, which belong to 24
      genera of fungi, were isolated from this crop. Of these fungi, 51 species and two
      varieties are considered new for this crop, whereas seven genera and 13 species
      are new to the mycoflora of the Sudan. The genus Aspergillus (13 species and 6
      varieties) which comprising 44% of the total colony count was the most prevalent
      genus followed by Rhizopus (2 species, 19%), Penicillium (6 species) and Fusarium
      (8 species) (12%), Chaetomium (3 species) and Cladosporium (5 species) (6%),
      where the 18 genera (1-4 species) showed very low level of incidence (19%). Of
      the possible pathogens of lentil plants, F. oxysporum the main cause of vascular
      wilt was recovered from seeds of this crop. Thin layer chromatographic analysis
      of chloroform extracts of 13 seed samples showed that only one samples was
      naturally contaminated with aflatoxins B1, B2, G1 and G2 (14.3 micrograms/kg).

PMID- 11307600
TI  - Reading Winnicott.

PMID- 11307601
TI  - Sexuality and attachment: a passionate relationship or a marriage of convenience?
AB  - The ubiquitous and persistent bodily urges of sexuality and their vicissitudes
      are explored in this paper, focusing on the complex relationship between
      libidinal desire and the attachment system, especially the latter's affect
      regulating function. This complicated interrelationship is highlighted with
      clinical vignettes. Implications for transference and countertransference are
      explored in the discussion of affect regulation and its possible sexual
      entwining. Clinical data is presented to highlight the plasticity of sexuality.
      Sexuality's protean nature allows for a reassessment of the case of Little Hans,
      with emphasis on the unique interconnections between sexuality and the vital need
      for an attachment relationship. Stressing such interconnections raises important
      questions about the traditional concept of psychosexual stages.

PMID- 11307602
TI  - Psychoanalysts' multiple relational perspectives.
AB  - The specific contribution of the person of the analyst--his or her attitudes,
      fantasies, and entire range of emotional responses to the patient--have become
      the subject of much investigation in psychoanalytic literature. This paper
      describes the phenomenon of distinct and sometimes contradictory self-experiences
      in analysts that develop as part of the moment-to-moment process of a
      predominantly adaptive coping mechanism. It is suggested that at any given point,
      the analyst's perspectives (reflecting various self-states), like those of the
      patient, are multiple, and that the analyst "choose" to place one such
      perspective at the center of experience. By choosing a certain self-state, the
      analyst can adopt, for example, a warm and loving stance with a regressed and
      demanding patient, or become harsh (e.g., setting boundaries, ending a session)
      with one who seeks affection and protection. This paper also suggests that the
      capacity to move between versions of self-states, to see them as complementary
      even when they are paradoxical, promotes a deeper understanding of paradoxes in
      the personality of the patient. Only when the analyst maintains a dialogue
      between various dissociated aspects of his or her analytic experience can a
      dialogue of this kind begin in the patient.

PMID- 11307603
TI  - Nonphysical touch: modes of containment and communication within the analytic
      process.
AB  - Psychoanalysis has struggled with issues of touching and being touched, and of
      holding and being held, since Freud's early essays toward "taking hold" of
      elusive thoughts through various means. More recently, observations of early
      dyadic interchanges between caretaker and child have illuminated how facets of
      the analytic process, such as the quality of gaze, tone, or empathic resonance,
      affect feelings of "being held" within the object world. These studies interplay
      with other analytic depictions and the work of affect theorists to show how
      meanings become represented and manifested over time through verbal versus
      nonverbal means. The author uses this literature to explore how our capacity to
      receive and transmit information cross-modally creates an interpenetration of
      meanings between self and other in the absence of actual physical contact.
      Clinical illustrations explore some of the meanings and uses of nonphysical modes
      of touch within the analytic environment.

PMID- 11307604
TI  - The holding environment and intersubjectivity.
AB  - The holding environment is explored in the context of the analytic dyad, where it
      is seen as rooted in the patient's need to be experientially known through the
      intersubjective interaction. In examining previous emphasis on holding as an
      optimally attuned empathic environment provided by the analyst, a broadened view
      of what constitutes a holding environment is presented, underscoring its
      interactional nature. A distinction is made between empathic holding based on the
      patient's expressed material, and holding that is generated through the analyst's
      intersubjective knowledge, gained via ongoing intersubjective engagements and
      enactments. It is argued that the unmediated connection to the patient's internal
      representations resulting from these intersubjective interactions, and the
      ensuing verbal exploration of them, can create a profound sense of being
      understood and thus held. A clinical process depicting the experience of holding
      in an intersubjective context is presented.

PMID- 11307605
TI  - Empathy and the unconscious.
AB  - The author examines the complex relationship between the concepts of empathy and
      unconscious, including exploration of topical, structural, and dynamic aspects;
      and the risk of oversimplification of empathy is discussed. Two clinical examples
      are then presented to demonstrate some of the complex factors that may contribute
      to or hinder the development and utilization of empathy by the analyst, many of
      which lie outside the analyst's conscious awareness.

PMID- 11307606
TI  - Recognition of basic fuchsin prestained microfissures of intravital origin with
      fluorescence microscopy: validation of a shortcut.
AB  - For 70 years it has been suspected that not all microfissures in histological
      bone sections are artifacts, but that some are provoked in vivo through
      repetitive stress. The development of undecalcified bone techniques and of the
      bulk staining technique has established a method for demonstrating the existence
      of intravital cracks and enhanced the discrimination towards artifactual
      microfissures in the load-bearing skeleton. Recently the presence of intravital
      microfissures has also been ascertained in temporal bones by these techniques.
      Due to the fluorescent properties of basic fuchsin it is possible to use
      epifluorescence microscopy for analysis of microfissures after bulk staining with
      basic fuchsin. This provides a more steady microscopic background and a sharper
      delineation of surface level structures since no projection from lower levels
      interfere. Artifactual cracks, which in transmitted light microscopy may look
      like darkly stained intravital microfissures due to refraction phenomena, become
      invisible or colorless. Epifluorescence microscopy enhances the detection of both
      smaller and larger prestained intravital microfissures, and leaves only a minor
      part of the cracks without certain categorization. The epifluorescence mode of
      analysis has the further advantage of being independent of slice thickness,
      making feasible whole-specimen analysis by serial stepwise grinding. The present
      study shows that the number and the length of microfissures in the human otic
      capsule, counted and measured under the epifluorescence microscope, equals
      numerically the findings in light microscopy, enabling the routine use of this
      mode of analysis. This may prove to be of particular value in the research into
      the etiology and pathogenesis of otosclerosis as well as perilymphatic fistulae.

PMID- 11307607
TI  - Transient evoked and distortion product otoacoustic emissions following
      successful stapes surgery.
AB  - BACKGROUND: The effect of stapes surgery on the recording of otoacoustic
      emissions is unknown. The aim of the present study was to evaluate the success of
      stapes surgery by using acoustically evoked otoacoustic emissions as an objective
      and fast method for postoperative hearing evaluation. METHODS: Transient evoked
      (TEOAE) and distortion product otoacoustic emissions (DPOAE) were measured
      consecutively in otosclerosis patients before as well as 3 and 6 months after
      stapes surgery. RESULTS: Air-bone gaps in the pure-tone audiograms were
      significantly reduced in all patients. TEOAEs and DPOAEs were not measurable
      preoperatively and were only evident in one patient postoperatively with low
      amplitudes in a narrow frequency range. CONCLUSIONS: Despite a subjective hearing
      improvement and a significant reduction of the conductive loss, otoacoustic
      emissions are only rarely evident after successful stapes surgery.

PMID- 11307608
TI  - Occurrence of NaK-ATPase isoforms during rat inner ear development and functional
      implications.
AB  - This study examined the presence of NaK-ATPase isoforms in the developing inner
      ear of the rat and studied the importance of functional subunit combinations in
      endolymph homeostasis. The findings were: (a) the combination alpha 1 beta 1 is
      found in epithelial, mesenchymal, and neural inner ear cells with an early
      starting expression 14 days postconception (dpc) in some endolymphatic sac cells;
      (b) from 1 day after birth (dab) expression of alpha 1 beta 2 is observed in
      marginal cells, vestibular dark cells, and certain vestibular nonsensory cells;
      (c) a transient expression of alpha 2 beta 1 is found in suprastrial fibrocytes
      and spiral ligament fibrocytes type II between 10 and 15 dab; (d) starting at 16
      dpc the combination alpha 3 beta 1 is uniquely expressed in inner ear neural
      cells (as in other neural tissues). In conclusion, during development a switch
      from alpha 2 beta 1 towards alpha 1 beta 1 is observed in suprastrial fibrocytes
      and in spiral ligament fibrocytes type II. Thus, according to the biochemical
      characteristics of these combinations, a switch towards a NaK-ATPase with higher
      capacity takes place. In addition, prominent expression of the alpha 1 beta 2
      combination in predominantly K+ ion transporting marginal and dark cells is in
      accordance with the characteristic of this combination and thus with the presumed
      function of these cells as important K+ suppliers for the endolymph. We believe
      this combination in certain vestibular nonsensory cells to be involved in K+
      sensing. Early expression of the alpha 1 beta 1 combination in the endolymphatic
      sac, prior to that in the other parts of the inner ear, suggests that this
      structure may be involved to some extent in the development of the vestibulum and
      cochlea.

PMID- 11307609
TI  - Cholesterol granuloma and aspergilloma of the maxillary sinus.
AB  - Cholesterol granuloma (CG) of the paranasal sinuses is rare. The proposed
      mechanisms of initiation are haemorrhage, impaired drainage and obstruction of
      ventilation. To the best of our knowledge, association of CG with a specific
      infection has not been described before. We have recently observed CG and
      aspergilloma of Aspergillus flavus type from the left maxillary sinus of a 58
      year-old male patient presenting with nasal obstruction, headache and postnasal
      discharge. Any causative relationship between the two findings is obscure. The
      suspected mechanisms underlying aspergilloma and CG of the paranasal sinuses
      seems similar, since there is obstruction of ventilation and drainage. The
      cholesterol accumulation cannot be attributed to cellular components or breakdown
      products of the aspergillus as the major sterol of the plasma membranes of fungi
      is ergosterol, not cholesterol.

PMID- 11307610
TI  - A basic protocol for functional assessment of voice pathology, especially for
      investigating the efficacy of (phonosurgical) treatments and evaluating new
      assessment techniques. Guideline elaborated by the Committee on Phoniatrics of
      the European Laryngological Society (ELS).
AB  - The proposal of this basic protocol is an attempt to reach better agreement and
      uniformity concerning the methodology for functional assessment of pathologic
      voices. The purpose is to allow relevant comparisons with the literature when
      presenting/publishing the results of voice treatment, e.g. a phonosurgical
      technique, or a new/improved instrument or procedure for investigating the
      pathological voice. Meta-analyses of the results of voice treatments are
      generally limited and may even be impossible owing to the major diversity in the
      ways functional outcomes are assessed. A multidimensional set of minimal basic
      measurements suitable for all "common" dysphonias is proposed. It includes five
      different approaches: perception (grade, roughness, breathiness),
      videostroboscopy (closure, regularity, mucosal wave and symmetry), acoustics
      (jitter, shimmer, Fo-range and softest intensity), aerodynamics (phonation
      quotient), and subjective rating by the patient. The protocol is elaborated on
      the basis of an exhaustive review of the literature, of the experience of the
      Committee members, and of plenary discussions within the European Laryngological
      Society. Instrumentation is kept to a minimum, but it is considered essential for
      professionals performing phonosurgery.

PMID- 11307611
TI  - Tumor markers in squamous cell carcinoma of the head and neck: clinical
      effectiveness and prognostic value.
AB  - Despite recent advances in tumor surgery and multimodal treatment regimens the
      prognosis of squamous cell carcinomas of the head and neck is still relatively
      poor and has shown only slow progress. Additional clinical and biological factors
      are therefore urgently needed that aid tumor diagnosis, early detection of tumor
      recurrences, prediction of the results of therapeutic interventions, and
      identification of subsets of patients with unfavorable outcome during follow-up.
      A tumor marker should fulfill the criteria of specificity and clinical
      effectiveness. So far none of the known serological and biological markers fits
      all these criteria. Although some biological markers can be determined
      serologically without the need for tumor tissue, their low specificity limits
      their applicability to early detection of tumor recurrences during follow-up. A
      large number of molecular or genetic markers have been examined in squamous cell
      carcinomas of the head and neck. All of these are controversial regarding their
      prognostic value and clinical effectiveness. UICC tumor stage and patient's age
      and performance still remain the basis for therapeutic decisions. Further search
      for more sensitive and specific markers is needed to improve individual treatment
      and prognostic statements.

PMID- 11307612
TI  - Comparison between nasogastric tube feeding and percutaneous fluoroscopic
      gastrostomy in advanced head and neck cancer patients.
AB  - Wasting is a major complication of advanced head and neck cancer and the aim of
      this study was to compare nasogastric tube feeding (NG) and percutaneous
      fluoroscopic gastrostomy (PFG) in these patients. The goal of these two methods
      of nutritional support was to improve or maintain the initial nutritional status
      during treatment. A total of 90 patients, all stage IV oropharynx or hypopharynx
      tumor, were reviewed from a prospective databank. All these patients were treated
      by concomitant chemotherapy and twice-daily continuous radiotherapy with no
      acceleration. Fifty patients were managed by PFG, and the rest by NG. Mechanical
      failure, duration of feeding, complications, nutritional evaluation and quality
      of life were analysed. Mechanical failure occurred in 32 of the 40 NG patients
      and in seven of the gastrostomy group. In the PFG group, 80% of patients
      conserved their nutritional support after the end of the radiotherapy, none
      patient in the NG group. In the PFG group, two presented a wound infection and
      six had aspiration pneumonia while in the NG group, 21 had aspiration pneumonia
      probably due to the NG tube (gastroesophageal reflux). The feeding methods were
      found to be equally effective at maintaining body weight and body mass index at
      time 1 (3 weeks) and at time 2 (6 weeks). Advantages were associated with PFG
      cosmesis, mobility and quality of life. PFG is a safe and effective method of
      providing enteral nutrition during treatment to patients with advanced head and
      neck cancer and offers important advantages over NG.

PMID- 11307613
TI  - Primary papillary adenocarcinoma confined to the middle ear and mastoid.
AB  - Primary adenocarcinoma is a rare tumor of the middle ear and temporal bone; its
      most frequent symptoms are hearing loss, otalgia, and facial paralysis. Otoscopic
      examination of a 27-year-old man revealed purulent discharge in the ear canal,
      diffuse edema, and hypertrophy of the right tympanic membrane. He presented with
      a grade III (House-Brachman) facial paralysis and right conductive hearing loss
      with a history of aural discharge for 6 months, otalgia, and facial weakness for
      2 days. Computed tomography of the temporal bone showed an opacity filling the
      tympanic cavity, antrum, and aditus. Tympanotomy revealed diffuse edema of the
      middle ear mucosa, and granulation tissue was encountered during mastoidectomy
      filling the antrum and periantral cells and eroding the fallopian canal at the
      level of the oval window. After the histopathological examination revealed
      papillary adenocarcinoma, a subtotal temporal bone resection, facial nerve
      segmenter resection, and end-to-end anastomosis of the facial with the
      hypoglossal nerves were performed. The importance of histopathological
      examination in all cases of chronic otitis media with granulation tissue is
      stressed.

PMID- 11307614
TI  - Quality of life after treatment for early laryngeal carcinoma.
AB  - Radiotherapy and surgery for early laryngeal cancer achieve comparably good
      results in patient survival, and the choice of treatment between them is being
      influenced increasingly by the expected voice quality and quality of life (QoL).
      The superiority of vocal function after radiotherapy has been shown in previous
      objective voice assessment studies. This study compared the QoL of long-term
      survivors after endoscopic laser surgery or radiotherapy for early laryngeal
      carcinoma. QoL was evaluated with two validated questionnaires: the global EORTC
      QLQ-C30 and the head- and neck-specific EORTC QLQ-H&N35. A total of 62 patients
      were included. Among 56 patients completing the questionnaires (90% completion
      rate) 40 were treated by endoscopic CO2 laser surgery and 16 with radiation
      therapy. All 56 patients showed a good global QoL with no significant difference
      between the two treatment modalities. The head- and neck-specific evaluation
      revealed significantly better scores for surgically treated patients in questions
      about swallowing of solid food, xerostomia, and tooth problems, but no difference
      in questions about voice quality. Both treatment modalities achieve good QoL
      after treatment of early laryngeal tumors. Irradiated patients mainly complain
      about xerostomia related problems. In contrast to objective measurements long
      term survivors after surgery do not rate their voice poorer than irradiated
      patients. The EORTC questionnaires are validated and useful tools in assessing
      QoL and should further be used in prospective trials.

PMID- 11307615
TI  - Promoter hypermethylation and homozygous deletion of the p14ARF and p16INK4a
      genes in oligodendrogliomas.
AB  - The INK4a/ARF locus on chromosome 9p21 encodes two gene products that are
      involved in cell cycle regulation through inhibition of CDK4-mediated RB
      phosphorylation (p16INK4a) and binding to MDM2 leading to p53 stabilization
      (p14ARF). The locus is deleted in up to 25% of oligodendrogliomas and 50% of
      anaplastic oligodendrogliomas, but little is known on the frequency of gene
      silencing by DNA methylation. We assessed promoter hypermethylation of p14ARF and
      p16INK4a using methylation-specific PCR, and homozygous deletion of the p14ARF
      and p16INK4a genes by differential PCR in 29 oligodendrogliomas (WHO grade II)
      and 20 anaplastic oligodendrogliomas (WHO grade III). Promoter hypermethylation
      of the p14ARF gene was detected in 6/29 (21%) oligodendrogliomas and 3/20 (15%)
      anaplastic oligodendrogliomas. None of the oligodendrogliomas and only 1 out of
      20 anaplastic oligodendrogliomas showed hypermethylation of p16INK4a. Homozygous
      deletion was not detected in any of the WHO grade II oligodendrogliomas but was
      present in 5/20 (25%) anaplastic oligodendrogliomas and always affected both
      genes. In one tumor containing distinct areas with and without anaplasia, p14ARF
      hypermethylation was detected in the WHO grade II area, while homozygous co
      deletion of p14ARF and p16INK4a was found in the region with anaplastic features
      (grade III). These data suggest that aberrant p14ARF expression due to
      hypermethylation is the earliest INK4a/ARF change in the evolution of
      oligodendrogliomas, while the presence of p14ARF and p16INK4a deletions indicates
      progression to anaplastic oligodendroglioma.

PMID- 11307616
TI  - P39 immunoreactivity in glial cytoplasmic inclusions in brains with multiple
      system atrophy.
AB  - Glial cytoplasmic inclusions (GCIs) characteristically occur in the
      oligodendrocytes of patients with multiple system atrophy (MSA). Cyclin-dependent
      kinase 5 (Cdk5) regulates cytoskeletal dynamism through phosphorylation of
      cytoskeletal proteins such as neurofilament proteins, tau and microtubule
      associated protein 2. We examined the immunohistochemical localization of p39, a
      Cdk5 activator, in human brain specimens obtained post mortem from controls and
      patients with MSA. Among control specimens, p39 immunoreactivity was found in
      some neuronal somata and axons. Similar immunoreactivity was detected in MSA
      neuronal cell bodies and axons, but a number of inclusions were heavily labeled.
      These results suggest that p39 and Cdk5 are up-regulated in oligodendrocytes and
      may be involved in the formation of GCIs through phosphorylation of cytoskeletal
      proteins in oligodendrocytes in MSA.

PMID- 11307617
TI  - alpha-synuclein immunopositive Parkinson's disease-related inclusion bodies in
      lower brain stem nuclei.
AB  - Advanced silver stains and immunohistochemical reactions against alpha-synuclein
      were used to detect Parkinson's disease-related cytoskeletal abnormalities in
      select lower brain stem nuclei. Various types of inclusion bodies including
      inconspicuous and heretofore unnoted granular particles and thread-like Lewy
      neurites were visualized. Of the nuclei investigated (gigantocellular reticular
      nucleus, bulbar raphe nuclei, coeruleus-subcoeruleus area), only lipofuscin- or
      neuromelanin-laden neuronal types showed a propensity to develop the pathological
      changes. Neuronal types devoid of pigment deposits remained free of the
      cytoskeletal abnormalities. Fine, dust-like particles and small globular Lewy
      bodies were encountered solely within the limits of intraneuronal lipofuscin or
      neuromelanin deposits.

PMID- 11307618
TI  - Developmental expression of the tuberous sclerosis proteins tuberin and hamartin.
AB  - Tuberous sclerosis complex is an autosomal dominant multisystem disorder,
      characterized by the development of hamartomas in multiple organs, primarily the
      skin, heart, kidney, and brain. The tuberous sclerosis genes, TSC1 and TSC2,
      encode hamartin and tuberin, respectively. Employing specific antibodies for
      hamartin and tuberin, we analyzed the expression of these two proteins by Western
      blot analyses in normal developing human and rat tissues. Both proteins are
      expressed ubiquitously in human fetal tissues and placenta, but are expressed at
      relatively low levels in human adult tissues, except brain. Similarly, high
      expression of these two proteins is observed in rat embryonic tissues, with a
      progressive decline after birth. To better characterize the developmental
      expression of tuberin and hamartin, we conducted a detailed study in rat tissues
      from embryonic day 13 to adult by Western blot analysis and immunohistochemistry.
      Immunohistochemical staining of rat tissues for tuberin and hamartin revealed
      tissue-specific expression patterns throughout development. Both tuberin and
      hamartin are expressed in epithelia, muscle (smooth, cardiac and skeletal muscle)
      and the nervous system (neurons, glia, choroid plexus and arachnoid). Except for
      the central nervous system, immunostaining intensity declines with age,
      confirming the protein blot analysis. These results indicate that tuberin and
      hamartin may play a critical role in development, and thus provide a framework
      for understanding the developmental and hamartomatous manifestations of tuberous
      sclerosis. These findings also suggest that tuberin and hamartin have additional
      functions in the adult brain, consistent with the marked neurological problems
      that afflict many patients with tuberous sclerosis.

PMID- 11307619
TI  - Alzheimer morphology is not increased in dialysis-associated encephalopathy and
      long-term hemodialysis.
AB  - This study examines the role of aluminium in the etiology of Alzheimer's disease
      (AD). Brains taken at autopsy (n = 50) from patients with a history of long-term
      hemodialysis (HD) and intake of aluminium (Al)-containing drugs were examined by
      light microscopy. Using our modified silver stain we have been able to
      demonstrate and clearly discriminate between AD changes and dialysis-associated
      encephalopathy (DAE) on paraffin sections; evaluation was done with a 3-point
      scale. DAE morphology is characterized by lysosome-derived intracytoplasmic, Al
      containing, pathognomonic, argyrophilic inclusions in choroid plexus epithelia,
      cortical glia and neurons. A statistically significant difference was found
      between the amounts of drug-related Al ingested and the degree of DAE-related
      morphological change (P < 0.001). On the other hand no apparent microscopical
      increase in AD morphology was found. No AD changes were seen whatsoever in
      patients under the age of 60, despite a history of long-term HD with ingestion of
      "pure" Al up to 2.5 kg. Patients over 60 years of age occasionally presented with
      sparse deposits of beta A4 amyloid (beta A4) and/or a low incidence of AD-type
      neurofibrillary tangles (NFT). In accordance with CERAD criteria these were
      identified as normal, age-related phenomena (P < 0.001 for beta A4; P < 0.001 for
      NFT). Rare, isolated cases from a group of 127 long-term hemodialyzed patients
      have been reported previously, who presented with intermingled, clearly
      distinguishable lesions of both age-related AD morphology and DAE changes.
      Comparison of AD morphology with an age-matched control group was not
      statistically significant (P > 0.6 for beta A4, P > 0.7 for NFT). In our
      experience, Al does not cause an increase in AD morphology, at least not in terms
      of bioavailable Al in drugs or as a result of long-term HD.

PMID- 11307620
TI  - Lovastatin and phenylacetate induce apoptosis, but not differentiation, in human
      malignant glioma cells.
AB  - Induction of differentiation is an attractive approach to the management of
      infiltrative tumors such as malignant glioma. Here, we report that lovastatin and
      phenylacetate induce apoptosis, but fail to induce differentiation, in malignant
      glioma cell lines and untransformed rat astrocytes. Lovastatin and phenylacetate
      promote p21 accumulation but fail to induce cell cycle arrest. BCL-2 gene
      transfer inhibits apoptosis induced by lovastatin but not apoptosis induced by
      phenylacetate. Wild-type p53 gene transfer promotes lovastatin-induced apoptosis
      in p53 wild-type LN-229 cells but not in p53 mutant T98G cells. Phenylacetate
      induced apoptosis is attenuated by wild-type p53 gene transfer in both cell
      lines. Neither lovastatin nor phenylacetate modulate glioma cell sensitivity to
      CD95 ligand-induced apoptosis or cancer chemotherapy. Thus, this study provides
      no rationale for clinical trials of lovastatin or phenylacetate in the
      differentiation therapy of malignant glioma. We conclude that neoplastic glioma
      cells as well as untransformed rat astrocytes are refractory to the induction of
      differentiation by lovastatin and phenylacetate.

PMID- 11307621
TI  - A lysosomal storage disease of Romney sheep that resembles human type 3 GM1
      gangliosidosis.
AB  - During a large neuropathological survey of clinically normal sheep for evidence
      of scrapie, three adult Romney ewes from the same farm were found to have
      populations of distended neurons containing granular eosinophilic storage
      material. The affected neurons were confined to the striatum. The granules had
      the tinctorial properties of glycolipid and the ultrastructural appearance of
      spherical bodies containing concentric membranous whorls. The bodies resembled
      those of GM1 gangliosidosis. The restricted neuroanatomical distribution of
      changes together with the age of the sheep suggests a similarity to human type 3
      GM1 gangliosidosis, which has not previously been reported in animals.

PMID- 11307622
TI  - Brain-derived neurotrophic factor reduces cortical cell death by ischemia after
      middle cerebral artery occlusion in the rat.
AB  - Stroke is the major cause of adult brain dysfunction. In an experimental approach
      to evaluate the possible beneficial effects of administration of neurotrophic
      factors in stroke, we have used a model of distal middle cerebral artery (MCA)
      occlusion in adult rats. In this model, we found: (1) a permanent reduction of
      brain-derived neurotrophic factor (BDNF) and its full-length receptor, TrkB, in
      the infarcted core; (2) a transient increase in BDNF immunoreactivity in the
      internal region of the border of the infarct (penumbra area) at 12 h after MCA
      occlusion; (3) increased truncated TrkB immunoreactivity in astrocytes
      surrounding the area of the infarction; and (4) increased full-length TrkB
      immunoreactivity in scattered neurons, distant from the infarct, in ipsilateral
      and contralateral cortices at 24 and 48 h after MCA occlusion. We next studied
      the regulation of TrkB expression by BDNF, after ischemia, and its
      neuroprotective effects in vivo. In control non-ischemic rats, grafting of mock-
      or BDNF-transfected fibroblasts (F3A-MT or F3N-BDNF cell lines, respectively) in
      the medial part of the somatosensory cortex increased truncated TrkB
      immunoreactivity in neighboring astrocytes. Grafting alone also increased full
      length TrkB in the vicinity of the mock graft (at 24 and 48 h) and the BDNF
      grafted graft (at 4 days). Interestingly, ischemic animals grafted with the mock
      transfected cell line did not show any further regulation of TrkB receptors.
      However, ischemic animals grafted with the BDNF cell line showed an up-regulation
      of full-length TrkB expression in neurons located in the internal border of the
      infarct. Analysis of nuclear DNA fragmentation in situ, combined with microtubule
      associated protein 2 immunohistochemistry, revealed that most cells dying in the
      borders of the infarct (penumbra area) at 48 h following MCA occlusion were
      neurons. No differences in the infarct size were found between MCA occluded, mock
      transfected MCA-occluded, and BDNF-transfected MCA-occluded rats. Moreover, cell
      death was similar in nongrafted and mock-grafted rats subjected to MCA occlusion.
      However, the number of cells with nuclear DNA breaks was significantly reduced in
      the penumbra area close to the BDNF graft in ischemic rats. Thus, our results
      show that BDNF specifically up-regulates its full-length TrkB receptor in
      cortical neurons of the penumbra area and prevents their death in an in vivo
      model of focal ischemia.

PMID- 11307623
TI  - Miller Fisher syndrome: immunofluorescence and immunoelectron microscopic
      localization of IgG at the mouse neuromuscular junction.
AB  - In vitro electrophysiological experiments have demonstrated that IgG antibodies
      from patients with Miller Fisher syndrome (MFS) impair neuromuscular transmission
      by a fast and completely reversible combined pre- and postsynaptic blockade. In
      this study we investigated the cellular and subcellular binding sites of IgG from
      four MFS patients at the mouse hemidiaphragm by immunofluorescence and
      immunoelectron microscopy. IgG from all patients produced significant
      immunostaining at the neuromuscular junction, whereas sera from healthy
      volunteers or from patients with other neurological diseases did not stain
      neuromuscular junction. Immunoelectron microscopy revealed that, when living
      hemidiaphragms were incubated with IgG from MFS patients, labeling was found on
      both pre- and postsynaptic membranes of the neuromuscular junction, whereas
      terminal Schwann cells and the basal lamina covering the synaptic membranes were
      not labeled. These findings demonstrate that IgG from MFS patients binds to
      synaptic membranes of the neuromuscular junction where it might interfere with
      the function of both the pre- and postsynaptic activities.

PMID- 11307624
TI  - Increased microglia proliferation separates pilocytic astrocytomas from diffuse
      astrocytomas: a double labeling study.
AB  - It is not known how many non-tumorous cells in gliomas contribute to the
      proliferation rate. We investigated the proliferative activity of microglia in an
      immunohistochemical double-labeling study of pilocytic astrocytomas and
      astrocytomas WHO grade II-IV using the antibodies MIB-1 (Ki67) as proliferation
      marker and Ki-M1P (CD68) as microglia marker. We found the highest indices of
      proliferating microglia in pilocytic astrocytomas with an average rate of 32% (+/
      6.8) of all proliferating cells. In contrast, the proliferation indices of
      microglia were lowest in fibrillary astrocytomas with 8.6% (+/- 2.5) of all
      proliferating cells. In anaplastic astrocytomas and glioblastomas the percentage
      of proliferating microglia showed a slight increase to 8.8% (+/- 3.6) and 13.4%
      (+/- 8.7), respectively. We conclude that microglial cells in astrocytic brain
      tumors proliferate and show different proliferative activities at different
      grades of malignancy with the highest rates of proliferating microglia especially
      in pilocytic astrocytomas. Thus, the proliferation rate does not solely reflect
      the proliferation of tumor cells, but also of non-tumorous cells. This should be
      considered in particular when proliferation rates are used as a criterion for
      prognosis and grading of pilocytic astrocytomas.

PMID- 11307625
TI  - Local distribution of microglia in the normal adult human central nervous system
      differs by up to one order of magnitude.
AB  - Although microglia are considered to be a sensitive sensor for pathological
      processes in the central nervous system, there are only a few studies about the
      distribution and density of microglia in the normal human brain. Therefore, a
      study of local density of microglial cells was conducted by investigating 20
      normal human brains with no clinical neurological symptoms or diseases and no
      neuropathological alterations. Microglial cells were visualized by immunolabeling
      of proteins which are known to be expressed either constitutively or
      facultatively, such as CD68, major histocompatibility complex class II (MHC-II),
      leukocyte common antigen (LCA), leukocyte chemotactic factor (LCF), macrophage
      inhibitory factor-related protein (MRP) 8, MRP14, CD4 and allograft-inflammatory
      factor-1 (AIF-1). CD68, MHC-II and AIF-1 showed the highest densities with
      significant regional differences ranging from 0.5% to 16.6% of all cells in the
      brain parenchyma with significantly more microglia in white than in gray matter.
      LCF and LCA showed a similar pattern of distribution as the proteins described
      above, but with lower percentages of microglial cells. CD4 was not found in the
      brain parenchyma. We conclude that CD68, MHC-II and AIF-1 define the main
      microglial cell population, whereas LCF and LCA are expressed by a subpopulation
      of microglial cells. The brains showed no or a negligible vascular expression of
      MRP8 and MRP14. Information about the local microglia density in the normal human
      brain can serve as a reference for the evaluation of pathological microglial
      responses.

PMID- 11307626
TI  - Frontotemporal dementia: evidence for impairment of ascending serotoninergic but
      not noradrenergic innervation. Immunocytochemical and quantitative study using a
      graph method.
AB  - A graph method was employed to analyze the spatial neuronal patterns of nuclear
      grays of the pontine tegmentum with ascending aminergic projections to the
      forebrain in 12 cases of frontotemporal dementia (FTD). The nuclear grays
      examined were the nucleus centralis superior (NCS), a part of the nucleus raphae
      dorsalis (NRD), and the locus coeruleus (LC). The results were compared with 30
      cases of Alzheimer's disease (AD) and 35 non-demented controls. In addition to
      the graph evaluations, neuronal cytoplasmic inclusion bodies were stained by
      silver impregnation and ubiquitin (Ub) and tau immunohistochemistry. The FTD
      cases showed a significant, 40%, decline in number of neurons in the NCS and NRD,
      while the LC was spared. The magnitude of neuronal loss matched that of AD where,
      by contrast, the LC was also severely changed. Amyloid deposition and Alzheimer
      neurofibrillary tangles occurred in the aminergic nuclei almost exclusively in AD
      and, to a minor extent, in some aged controls. No cytoplasmic inclusion bodies
      were found in the aminergic nuclei of the FTD cases. However, 6 cases had Ub
      positive but tau-negative neuronal inclusions in the hippocampal dentate fascia
      and in layer 2 of the prefrontal isocortex, and 3 showed clinical and
      histological signs of motor neuron disease. Our results suggest that the
      serotoninergic raphe nuclei with ascending projections to the forebrain, but not
      the LC, become directly or indirectly involved in frontotemporal dementia both
      with and without motor neuron disease.

PMID- 11307627
TI  - Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain.
AB  - Using immunohistochemistry, expression of erythropoietin (EPO), a hypoxia
      inducible neuroprotective factor, and its receptor (EPOR) were investigated in
      human brain tissue after ischemia/hypoxia. Autopsy brains of neuropathologically
      normal subjects were compared to those with ischemic infarcts or hypoxic damage.
      In normal brain, weak EPO/EPOR immunoreactivity was mainly neuronal. In fresh
      infarcts, EPO immunoreactivity appeared in vascular endothelium, EPOR in
      microvessels and neuronal fibers. In older infarcts reactive astrocytes exhibited
      EPO/EPOR immunoreactivity. Acute hypoxic brain damage was associated with
      vascular EPO expression, older hypoxic damage with EPO/EPOR immunoreactivity in
      reactive astrocytes. The pronounced up-regulation of EPO/EPOR in human
      ischemic/hypoxic brains underlines their role as an endogenous neuroprotective
      system and suggests a novel therapeutic potential in cerebrovascular disease for
      EPO, a clinically well-characterized and safe compound.

PMID- 11307628
TI  - Mixed pituitary adenoma-gangliocytoma in a female albino rat.
AB  - A mixed intrasellar pituitary adenoma-gangliocytoma was found incidentally in an
      aged female Sprague-Dawley-derived rat. The animal was killed at the end of a 104
      week carcinogenicity study. At necropsy, the pituitary fossa was occupied by a
      large, hemorrhagic nodule compressing and displacing the base of the brain. The
      lesion consisted of large areas of a prolactin-secreting adenoma surrounding a
      central island of gangliocytoma. In the latter, ganglion-like cells of varying
      size exhibited, occasionally, beta-tubulin and neurofilament protein
      immunoreactivity in their perikarya, while their cell processes expressed intense
      neurofilament immunoreactivity. Accompanying satellite cells in the neuropil
      immunostained for glial acidic and S-100 proteins. To the best of our knowledge,
      the presence of mixed pituitary adenoma-gangliocytoma has not been previously
      reported in rats.

PMID- 11307629
TI  - Bunina body in frontal lobe dementia without clinical manifestations of motor
      neuron disease.
AB  - We report here an early autopsy case of a 60-year-old woman clinically diagnosed
      as having frontal lobe dementia without other neurological deficits. Postmortem
      examination revealed mild spongiosis in layers II and III of the frontal cortex,
      together with depletion of melanin-containing neurons in the substantia nigra. In
      addition to ubiquitin-positive neurites, ubiquitin-positive, tau-negative
      inclusions, which were previously considered to be a hallmark for motor neuron
      disease with or without dementia, were identified in neurons of the hippocampal
      dentate gyrus and of the temporal cortex. Although the patient lacked lower motor
      symptoms, the presence of Bunina bodies identified in the hypoglossal nuclei
      further supported the relationship of this case to motor neuron disease. Bunina
      bodies might be present in some cases of frontal lobe dementia. The presence or
      absence of Bunina bodies should be scrutinized even in cases without motor
      symptoms. In this case, creatine kinase of skeletal muscle origin was elevated,
      which might also be a potential indicator that suggests subclinical involvement
      of lower motor neurons.

PMID- 11307630
TI  - Co-localization of alpha-synuclein and phosphorylated tau in neuronal and glial
      cytoplasmic inclusions in a patient with multiple system atrophy of long
      duration.
AB  - Neuronal and glial cytoplasmic inclusions (NCIs and GCIs), which contain alpha
      synuclein as a major component, are characteristic cytopathological features of
      multiple system atrophy (MSA). We report MSA of 19 years' duration in a 73-year
      old woman. Her initial symptom was parkinsonism, with dementia appearing about 8
      years later. Postmortem examination showed marked atrophy of the frontal and
      temporal white matter and limbic system, in addition to the pathology typical of
      MSA. In the limbic system, severe neuronal loss and astrocytosis were observed,
      and the remaining neurons often had lightly eosinophilic, spherical cytoplasmic
      inclusions. Interestingly, a double-labeling immunofluorescence study revealed
      that the NCIs in the dentate gyrus and amygdaloid nucleus, and the GCIs in the
      frontal and temporal white matter often expressed both alpha-synuclein NACP-5 and
      phosphorylated tau AT8 epitopes. Double-immunolabeling electron microscopy of the
      NCIs in the dentate gyrus and the GCIs in the temporal white matter clearly
      revealed labeling of their constituent granule-associated filaments with NACP-5,
      and some of them were also labeled with AT8. These findings strongly suggested
      that some alpha-synuclein filaments were decorated with phosphorylated tau
      without formation of fibrils such as paired helical filaments. Immunoblotting of
      sarkosyl-insoluble tau indicated that the accumulated tau consisted mainly of
      four-repeat tau isoforms of 383 amino acids and 412 amino acids. We consider that
      the limbic system can be a major site of neurodegeneration in MSA of long
      duration. The mechanisms of such abnormal tau accumulation in the NCIs and GCIs
      are unknown.

PMID- 11307631
TI  - Inhalation toxicity of Dioxole and Dioxolane compounds in the rat.
AB  - Four chemicals (Dioxole 418, Dioxolane 418, Dioxolane 416 and Dioxolane 456)
      which are used as stabilizers in highresolution image were tested or both their
      acute and repeated inhalation toxicity in the rat using nose-only exposures.
      Acute studies determined the lethal concentrations following a single 4-hour
      exposure; repeated exposure inhalation studies determined the potency and target
      tissue(s) following 6-hour/day exposures, 5 days/week for 2 weeks. Each of the
      chemicals was at least mildly toxic acutely with approximate lethal
      concentrations of > 1,500 ppm for Dioxole 418, 1,300 ppm for Dioxolane 418, 1,700
      ppm for Dioxolane 416, and 4,300 ppm for Dioxolane 456. No specific unusual
      clinical signs of response were seen in the rats exposed acutely. Repeated
      exposures with Dioxole 418 and Dioxolane 418 resulted in no evidence of toxicity
      with NOAEL's being 440 and 500 ppm respectively (the highest concentrations
      tested). Repeated exposures to 250 ppm Dioxolane 456 were not tolerated with
      mortalities observed after exposure. Severe bone marrow hypoplasia along with
      reductions in platelet and neutrophil counts were observed at this concentration
      with less severe hemopoietic changes seen also at 10 and 51 ppm. The no-effect
      level for Dioxolane 456 was determined to be 10 ppm in female rats and I ppm in
      males. The same hemopoietic effects were seen with Dioxolane 416 at exposures of
      53 ppm or greater in males but not in females exposed to 53 ppm Dioxolane 416.
      Hepatocellular hypertrophy and depression of serum alkaline phosphatase activity
      were seen in male rats exposed to 500 but not 53 ppm Dioxolane 416. Testicular
      degeneration was also seen in rats exposed to 500 ppm Dioxolane 416. The NOAEL
      was 5 ppm for the chemical.

PMID- 11307632
TI  - Evaluation of the immunomodulatory effects of the macrolide antibiotic,
      clarithromycin, in female B6C3F1 mice: a 28-day oral gavage study.
AB  - The macrolide antibiotic, clarithromycin, is used extensively to treat bacterial
      infections associated with pneumonia, duodenal ulcers, and the advanced stages of
      human immunodeficiency viral (HIV) infection. In addition to its antimicrobial
      properties, several studies have indicated that clarithromycin also has anti
      inflammatory and immunomodulatory properties. In this study, clarithromycin's
      immunomodulatory properties were evaluated using female B6C3F1 mice and a panel
      of immune assays that were designed to evaluate potential changes in innate, and
      acquired cellular and humoral immune responses. Female B6C3F1 mice were treated
      daily by gavage with clarithromycin (0, 125, 250, and 500 mg/kg) for 28 days then
      evaluated for immunomodulation. Minimal immunological changes were observed after
      28 days of treatment. A slight increase in the number of spleen antibody-forming
      cells was observed at the 250 mg/kg treatment level, but not at other doses.
      Serum IgM levels were unaffected by the clarithromycin treatment. A significant
      increase in the number of splenic macrophages was also observed in mice treated
      with 125 mg/kg of clarithromycin, but this increase was not observed at the other
      treatment levels. Innate and cell-mediated immunity, as measured by natural
      killer cell activity, and mixed leukocyte and cytotoxic T cell response,
      respectively, were unchanged following treatment with clarithromycin. These
      results suggest that the immune system is not a target for clarithromycin at
      doses of 500 mg/kg or below.

PMID- 11307633
TI  - Effects of cresols (o-, m-, and p-isomers) on the bioenergetic system in isolated
      rat liver mitochondria.
AB  - It is known that o-, m- and p-cresols exert a toxic effect on rat liver cells.
      However, there is little information on the mechanism for the hepatotoxicity of
      cresols. We, therefore, investigated the effects of o-, m-, and p-cresols on the
      bioenergetic system using isolated rat liver mitochondria. When o-, m- or p
      cresol was added to liver mitochondria with glutamate or succinate at
      concentrations of 0.3 to 6.0 mumol/mg protein, each cresol isomer reduced the
      rate of state 3 respiration dose-dependently. Three cresol isomers at 6.0
      mumol/mg protein each inhibited state 3 respiration in liver mitochondria with
      glutamate or succinate by about 60 or 20%, respectively. The three isomers
      affected NAD- and succinate-linked respirations in liver mitochondria, by which
      the respiratory control ratio was dose-dependently attenuated. The inhibitory
      effects of o-, m- and p-cresols on the NAD-linked respiration were stronger than
      those on the succinate-linked respiration. However, three cresol isomers had
      little effect on the P/O ratio in liver mitochondria with glutamate or succinate.
      Three cresol isomers at 15 mumol/mg protein each induced the swelling in the
      absence of Ca2+ in medium and accelerated the swelling of liver mitochondria in
      the presence of Ca2+ in medium. These results indicate that o-, m- and p-cresols
      inhibit liver mitochondrial respiration and induce or accelerate the swelling of
      liver mitochondria, and suggest that liver mitochondria may be one of the targets
      for the hepatotoxic actions of cresols.

PMID- 11307634
TI  - Placebo-controlled, blinded comparison of antenatal betamethasone on mouse liver
      development.
AB  - The objective of this investigation was to evaluate, in a placebo-controlled
      manner, the developing mouse liver after antenatal exposure either to a single
      dose or to a multidose of betamethasone. Ninety gravid CD-1 mice were randomly
      divided into three groups (n = 30/group) to receive either saline (0.25 mL s.c.)
      or betamethasone (0.10 mg s.c.) as a single dose on gestational day (GD) 14 of a
      19-day gestation or as a 0.10 mg dose given twice daily on GD 14 and on GD 15 (4
      doses). GD 0 is defined by the presence of a copulatory plug. These exposures of
      betamethasone cause fetal mouse lung maturation as would be observed in premature
      humans at 24-34 weeks of gestation. The livers were removed either from the
      fetuses on GD 16.5 or from the offspring on postnatal day 1, 3, 5, and 120.
      Special stains were used to evaluate hepatocyte architecture, glycoprotein and
      glycogen content, extramedullary hematopoiesis and iron storage. Hepatocyte
      intranuclear DNA content, cell size, and cell shape were measured by image
      analysis (CAS 200). At GD 16.5, betamethasone produced a significant decrease in
      the liver/body weight ratio that, when compared with the placebo group, was
      greater with the multidose (p < 0.01) than with the single dose (p < 0.05). 16.5
      GD single dose hepatocytes were smaller in size as compared to placebo without
      impact on intranuclear DNA (p < 0.01). Single dose PND 1 hepatocytes demonstrated
      an increase in intranuclear DNA as compared to placebo but without change in cell
      size (p < 0.001). The prenatal reduced liver weight recovered in the newborn
      period. No difference in microscopic architecture of the hepatocytes or
      histologic differences between either of the three treatment groups was found in
      glycogen deposition, extramedullary hematopoiesis or iron metabolism at GD 16.5
      and postnatally. It was concluded antenatal betamethasone can cause a decrease in
      the liver/body weight ratio in the fetal mouse that recovers eventually without
      any functional impact as assessed histologically.

PMID- 11307635
TI  - In vivo genotoxic effect of zinc sulfate in mouse peripheral blood leukocytes
      using Comet assay.
AB  - Single stranded DNA breaks induced by Zinc sulfate in mice has been studied in
      vivo using Alkaline Single Cell Gel Electrophoresis (Comet assay). Mice were
      administered orally with doses of 5.70, 8.55, 11.40, 14.25, 17.10 and 19.95 mg/kg
      body weight of zinc sulfate respectively. The samples of whole blood were
      collected at 24, 48, 72, 96 hr and first week post-treatment and the assay was
      carried out to determine single strand DNA breaks as represented by comet tail
      lengths. Results indicated a significant DNA damage at all the doses after
      treatment with zinc sulfate when compared to controls showing a clear dose
      dependent response (p < 0.05). A gradual decrease in the tail-lengths from 48 hr
      post-treatment onwards was observed indicating a time dependent decrease in the
      DNA damage. The study confirms that zinc sulfate causes significant DNA damage at
      the doses used as revealed by comet assay.

PMID- 11307636
TI  - Histologic study of a bovine demineralized bone matrix on bone repair process in
      rabbits calvaria.
AB  - The aim of this study was to evaluate histologically the bovine demineralized
      bone matrix, Osseobond, on bone repair process in rabbit's calvaria. Nine rabbits
      were used and two surgical defects were created on each calvaria, one was just
      filled with the animal blood and the other was filled with demineralized bone
      matrix. The animals were sacrificed in postoperative period of 3, 7, and 15
      weeks. Specimens on light microscopy analysis revealed that bone repair were
      improved on cavities filled with bovine demineralized bone matrix.

PMID- 11307637
TI  - Comparative evaluation of strength of various core restorative materials for
      endodontically treated anterior teeth.
AB  - In the present study, four restorative materials were used for the restoration of
      endodontically treated anterior teeth and their strength were compared with that
      of natural teeth. 100 freshly extracted Maxillary Central Incisors were used. The
      teeth were restored with Pin-retained amalgam-core buildups, Dowel-post with
      Glass ionomer-Amalgam alloy combination Cast Core build up. The natural tooth
      showed the maximum strength. Though some of the restorative materials showed
      promising results, none of them is able to show strength anywhere near to that of
      natural tooth.

PMID- 11307638
TI  - Knowledge of dental health and diseases among dental patients, a multicentre
      study in Saudi Arabia.
AB  - The aim of this study was to assess the knowledge of dental patients about dental
      health and diseases. A questionnaire was developed with three sets of questions,
      1-general knowledge of dental conditions, 2-use of alternate methods in
      prevention and treatment of dental diseases, 3-awareness about personal oral
      health. Six hundred questionnaires were distributed in 6 cities from 4 different
      regions (i.e. Makkah, Riyadh, Tabuk, Gizan). 367 respondents (61% response rate)
      constituted 233 (63.5%) male and 134 (36.5%) female with the age range 11-70
      years (mean 30 +/- 11.9). The data were analyzed by SPSS version 9.0 and results
      presented in frequency distributions. 99% male and 96% female considered their
      teeth for chewing food, 97% male and 96% female knew that increased carbohydrate
      intake and poor oral hygiene are related to tooth decay, 89% male and 96% female
      used toothbrush and paste to prevent dental diseases and 75% male and 66% female
      were regular user of miswak (chewing sticks.) 67% male and 59% female visit
      dentist, only in pain. 46% used miswak after their meals, only 14% of the
      subjects used miswak on their lingual and palatal surfaces of teeth, while 38% of
      the subjects used clove as remedy for toothache, 25.6% used saline and 10% used
      lemon for bleaching their teeth. 15% considered honey important for their good
      oral health. Regarding personal oral health, 35% had pain in gums, 36.8% were
      with bad breath, 28% had tooth hypersensitivity, and almost 50% used toothbrush
      twice daily while 42% had bleeding gums. It is important to note that knowledge
      and awareness about dental health and disease conditions are better in male
      subjects, dietary habits and oral hygiene methods need to be addressed in future
      investigations. There is a need to provide more health education to female
      subjects to improve their oral health.

PMID- 11307639
TI  - Awareness about biomedical waste management and infection control among dentists
      of a teaching hospital in New Delhi, India.
AB  - All 64 dentists working in a teaching hospital of New Delhi participated in a
      survey. A pre-tested self-administered questionnaire was used to assess knowledge
      and practices of biomedical waste management and infection control among these
      dentists. The results show that not all dentists were aware of the risks they
      were exposed to and only half of them observed infection control practices. In
      addition to this, majority of them were not aware of proper hospital waste
      management. The dentists need to be educated on Biomedical Waste (Management &
      Handling) Rules, 1998 through extensive training programme.

PMID- 11307641
TI  - I need an implant part! Who do I contact? What do I request?

PMID- 11307640
TI  - Local anaesthetic for minor oral surgical procedures. Review.
AB  - Pain following any surgical procedure is difficult to combat by man. Analgesics
      can be given for some amount of symptomatic relief. The need for a long lasting
      local anaesthetic is with the intention to reduce the most severe nature of pain,
      and decrease the analgesic consumption. This study was conducted to compare the
      efficacy of, Bupivacaine over Lidocaine for minor oral surgical procedures. The
      popularly used lidocaine works for 3 to 3.9 hours. This is not sufficient since
      the most severe nature of pain is felt six to eight hours post surgery, where as
      Bupivacaine has duration of action of seven to eight hours. Hence the post
      operative pain experienced following administration of bupivacaine was found to
      be considerably lesser in degree than compared to the lidocaine group. To avoid
      severe pain and discomfort to the patient following any minor oral surgical, the
      use of bupivacaine is recommended.

PMID- 11307642
TI  - Pain and dental implantology: sensory quantification and affective aspects. Part
      I: At the private dental office.
AB  - After an extensive review of the dental literature, few articles were found
      related to pain and implantology. Management of orofacial pain has traditionally
      been a difficult challenge for the dental-medical profession. Patients may be
      afraid of dental pain, particularly in cases of dental implantology. Therefore, a
      study to obtain more conclusive data was developed. Taking into account that the
      perception of pain and the threshold of pain vary among individuals, a 2-year
      clinical study was established in private practice utilizing a verbal method
      (double-blind). The study was used to quantify sensory and affective aspects of
      pain associated with dental implantology on 75 patients in a private dental
      office. All of the implants were placed by the same clinician. Data were recorded
      following a Pain Data Sheet designed for this particular study. The aim of this
      study was to obtain different aspects of data as follows: 1) Fear of the dentist
      and fear of dental implant procedures utilizing a descriptive scale of 1 to 10,
      with 1 indicative of no fear. 2) Dental areas and ridges: Dental pain, pain in
      edentulous areas, and pain in the implanted area utilizing a scale of 0 to 8,
      with 0 indicative of no pain. 3) Function and pain: during mastication,
      swallowing, speech, yawning, opening, closing, and lateral excursions and
      indication of cervical pain or back pain, each calibrated by the presence or
      absence of pain. 4) Palpation and pain of the temporomandibular joint, the
      temporal muscle, the area of the pterygoid muscles, masseter muscle, and
      sternocleidomastoid muscle, all calibrated on the indication of presence or
      absence of pain. 5) Others: ear pain, neuralgia, headaches, edema, and hematoma,
      calibrated on the basis of presence or absence. The aforementioned factors were
      evaluated immediately before surgery and after surgery, at 24 hours, and during a
      follow up for a period of 2 years at intervals of 1 week; 1, 2, 3, 4, and 6
      months; and 1 and 2 years after surgery. Also recorded were the uses of
      presurgical and postsurgical medication at the first and second surgical phases,
      age, sex, buccal opening, number and position of implants, previous dental
      experiences, and the psychological preparation for dental implant treatment. The
      results of the statistical analysis indicate no correlation between pain and
      dental implantology procedures, in a private dental practice, at the level of
      significance of P > .001.

PMID- 11307643
TI  - Maxillofacial surgical application of bone inductor materials.

PMID- 11307644
TI  - Immediate loading of implant-fixed mandibular prostheses: a prospective 18-month
      follow-up clinical study--preliminary report.
AB  - A prospective study was conducted on 13 consecutive patients who received
      immediately loaded mandibular fixed-implant prostheses. The exclusion criteria
      were 1) general: heavy smoking, demonstrated bruxism, or general ill health and
      2) local: lesions in the bone area to be implanted or inadequate morphology
      requiring augmentation techniques. After suturing the surgical wounds,
      impressions were taken, and transitional prostheses were screwed in within 2
      weeks of surgery. A total of 61 implants of four different designs were placed.
      Thirty-two of the implants were placed at the same time as performing the
      extractions of the residual dentition. In 13 of the implants, there was a 2-month
      period between extraction surgery and implantation. The other 16 implants were
      inserted in alveolar bone that had been edentulous for more than 12 months.
      Despite these differences, all 61 implants were immediately loaded. Parallel x
      rays were taken of the 13 patients at the time of transitional prosthesis
      placement, at the time of definite prosthesis placement, and 6 months later at
      the first control. During the 18-month follow-up period, two implants failed, and
      the remaining 59 implants were found to be clinically immobile, asymptomatic, and
      free of any radiolucency, giving a survival rate of 96.7%. Analysis of
      radiographic bone levels gives us a cumulative success rate of 93.4%. These
      figures are comparable to those obtained in similar studies and are no different
      than those from implant prostheses loaded in the conventional delayed manner.
      Based on these preliminary results, we can conclude that the immediate loading of
      mandibular implants is a viable and efficient approach.

PMID- 11307645
TI  - Advanced alveolar crest atrophy: an alternative treatment technique for maxilla
      and mandible.
AB  - A concept of oral implantology for the treatment of advanced crest atrophy is
      presented: The lateral insertion technique with disk-design implants is less
      invasive than bone grafting. An implant case demonstrates the simultaneous
      surgery of an edentulous maxilla and a mandible. Implant loading zones in the
      anterior and posterior areas of the arch are created with disk-design implants.
      Their support is tricortical or multicortical. Seven to eight days after surgery,
      the implants are immediately loaded with fixed esthetic temporaries. After
      another 40 days, the definitive restorations on the implants can be fabricated.
      The procedure is safe and shortens chairtime.

PMID- 11307646
TI  - Rehabilitation of a patient with severe dentoalveolar injuries: a case report
      with a 10-year follow-up.
AB  - This clinical report describes the emotional and physical rehabilitation of a
      young man. The impact of the injuries sustained and repeated failure of
      traditional dental treatment methods had caused the patient to become quite
      withdrawn. A successful outcome followed surgical placement of multiple titanium
      plasma-sprayed cylindrical fixtures in severely damaged dental supporting tissues
      to serve as intermediary abutments for complex maxillary and mandibular fixed
      prostheses. The loss of crestal bone during the postprosthetic years is
      determined. The advantages only implant dentistry could bring are identified.

PMID- 11307647
TI  - Restoration of the atrophied mandible using basal osseointegrated implants and
      fixed prosthetic superstructures.
AB  - The nonremovable reconstruction of the atrophic mandible is possible with basal
      osseointegrated implants in an immediate-load procedure. Between 4 and 5 implants
      are necessary to form a reliable foundation for a fixed bridge. The vertical
      dimension and the aesthetic appearance may be reconstructed in the desired way.

PMID- 11307648
TI  - Collagen membrane resorption in dogs: a comparative study.
AB  - Guided tissue barriers using materials such as collagen are used in the hope of
      excluding epithelium and the gingival corium from the root surface or alveolar
      bone to facilitate regeneration. Convention suggests that the longer a membrane
      remains intact, the better the regeneration results. The purpose of this study
      was to determine the resorption rates of various collagen membranes in the oral
      cavity of dogs. Twelve adult mongrel dogs had three different collagen membranes
      (BioGide, AlloDerm porcine-derived, and AlloDerm human-derived) randomly inserted
      and secured into surgical pouches made in their palates. Full-thickness tissue
      punch biopsy specimens taken at 1, 2, 3, or 4 months after surgery were evaluated
      histologically for membrane intactness and other associated changes. At 1 month,
      all membranes had slight to moderate degradation. At 2 months, all membranes had
      moderate to severe degradation with the exception of one AlloDerm human-derived
      membrane that was intact. At 3 months, all membranes had severe degradation to
      not identifiable. At 4 months, all membranes had severe degradation to completely
      absent. Blood vessel penetration varied from none to moderate. Inflammation was
      found in only two samples. In the dog, all three tested collagen membranes showed
      slight to moderate degradation at 1 month and were severely degraded to
      completely absent at 4 months. Within the limits of transferring animal data to
      humans, clinicians need to be aware of these resorption rates when selecting
      membranes for guided tissue and bone regeneration.

PMID- 11307649
TI  - Effects of a modified sandblasting surface treatment on topographic and chemical
      properties of titanium surface.
AB  - A modified sandblasting surface treatment (a noncoating, roughening surface
      modification of dental implants) has been developed that will overcome the
      defects of conventional coating techniques. To verify the feasibility and
      reliability of this method at the chemical and topographic levels, scanning
      electron microscopy, x-ray diffraction, and a titanium ion releasing test were
      used; the topography of titanium surface, the embedding of sandblasting
      particles, nonpollution of heteroelements, and anticorrosiveness of titanium were
      criteria. Results showed that the rough surface created by sandblast was rather
      irregular, full of sharp tips and many embedded sandblast particles, and its
      corrosive rate was increased. These characteristics were modified by oxalic acid
      attack; the contour of the rough surface became more regular and round, the
      embedded particles and the heteroelement pollution were thoroughly removed, and
      the Ti corrosive rate decreased dramatically. Oxalic acid attack modification
      also created numerous secondary micropores (2.0-micron diameter) on the basis of
      sandblasted surface macrotexture. This modified sandblasting surface treatment is
      feasible and reliable to apply to dental implants and does not decrease the
      biocompatibility of titanium.

PMID- 11307650
TI  - An assessment of implant coverage in dental benefit plans.
AB  - In the last 30 years, dental implantology has undergone widespread advances in
      technology and now complex, high-risk procedures are routine. Patients are
      becoming more vocal in their requests for this service from dentists in private
      practice and academic institutions. Unfortunately, although treatment modalities
      have improved, the cost for this service remains beyond the reach of the average
      patient. The purpose of this article is to assess the present status of implant
      coverage in dental benefit plans in the US.

PMID- 11307651
TI  - Survey of clinical members of the association of dental implantology in the
      United Kingdom: Part I. Levels of activity and experience in oral implantology.
AB  - The aims of this survey were to 1) determine recruitment rates of active oral
      implantologists, 2) establish the proportion of participants who carry out the
      surgical aspects of implantology, 3) quantify levels of surgical activity, 4)
      determine the type of qualifications held by this sample, and 5) identify the
      location of implant activity of clinical members of the Association of Dental
      Implantology (UK). Questionnaires were mailed to the 408 members of the ADI
      registered as clinical members of the ADI; data were collected between July 1998
      and May 1999. A response rate of 66.9% was achieved. Active members increased
      markedly from 1985 to 1995. Surgical activity and clinical experience varied
      widely: 32.9% had placed 100 to 499 implants, 29.8% had inserted 1 to 49
      implants, and 4.3% had inserted > or = 2,000 implants. The total number of
      implants inserted by this sample could only be estimated (between 51,000 and
      90,000). The majority of this sample possessed postgraduate qualifications,
      although only 2.6% possessed a degree in oral implantology. The data from this
      sample indicated that the recruitment rate to the ADI (UK) increased markedly
      between 1985 to 1995, after which it seems to have slowed down. Most of the
      respondents were involved in the surgical aspects of implantology, although the
      level of surgical involvement varied widely. The low incidence of postgraduate
      degrees in implantology might reflect the relatively limited opportunities
      currently available for such training in the UK.

PMID- 11307652
TI  - Nonsteroidal anti-inflammatory drugs and paracetamol in children.
AB  - The cyclooxygenase enzymes produce large amounts of prostaglandins in presence of
      tissue injury and inflammation. Prostaglandins exert their influence on nerve
      membrane excitability both at the peripheral site and at the spinal dorsal horn.
      Their key role in peripheral tissue inflammation and central sensitization
      warrants their incorporation in pain management strategies for children. As the
      COX2 isoenzyme is the main target for controlling hyperalgesia, nonsteroidal anti
      inflammatory drugs (NSAIDs) with high affinity for this enzyme will provide
      reliable antihyperalgesic effects. The benefits of NSAIDs for postsurgical pain
      therapy must be balanced against the risk of postoperative bleeding in children
      in whom any derangement of hemostasis could adversely affect outcome. If
      contraindications for NSAID use exist, paracetamol is the alternative.
      Paracetamol has potent antipyretic and analgesic effects, but no anti
      inflammatory effect. The rectal route of administration is notoriously unreliable
      for eliciting an analgesic effect and the oral route is to be preferred. The
      dosage of paracetamol must take into account the pharmacokinetic properties of
      the drug in children. The maximum daily dosage should not be exceeded to avoid
      excessive production of a hepatotoxic metabolite.

PMID- 11307653
TI  - Anaesthetic management of a child with type VIIc Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome type VIIc is characterized by altered tensile strength of
      connective tissue. Several severe complications exist but skin fragility is the
      origin of perioperative morbidity during routine procedures. We describe the
      difficulties encountered during the anaesthetic management of a child suffering
      from the disease, and suggest special care advices to avoid any skin injury.

PMID- 11307654
TI  - Miss-'n-mix and mimics.

PMID- 11307655
TI  - "Tibia cervicalis": an unusual cause of difficult intubation.

PMID- 11307657
TI  - Do guidelines for good clinical practice last forever?

PMID- 11307656
TI  - Intravenous tramadol compared to propacetamol for postoperative analgesia
      following thyroidectomy.
AB  - We compared the efficacy and side effects of propacetamol (P), an injectable
      prodrug of acetaminophen, 2 g and tramadol (T), a weak synthetic opioid, 1.5
      mg.kg-1, given intravenously following thyroidectomy. 80 patients were randomly
      assigned to blindly receive one dose of P or T on request in the PACU. Residual
      pain was treated with i.v. PCA morphine. Pain and patient satisfaction were
      assessed with Visual Analog Scales. Demographic and peroperative data were
      comparable in both groups. Although the morphine consumption was comparable (p =
      0.71), the decrease in VAS pain scores was significantly higher following
      tramadol (p = 0.03). More patients complained of nausea and vomiting (p = 0.01)
      during the first two hours following injection of tramadol, but there was no
      difference throughout the whole study. Oversedation was not observed in any
      group. We conclude that a single dose of tramadol provides a better quality of
      analgesia than propacetamol during the first six hours after thyroidectomy, but
      fails to ensure optimal analgesia, since VAS pain scores failed to fall below 3
      despite the use of supplemental morphine.

PMID- 11307658
TI  - Safety first--five years later. Belgian standards for patient safety in
      anaesthesia revisited.
AB  - Belgian Standards for Patient Safety in Anaesthesia, established in 1989 by a
      joint effort of the Belgian Professional Association of Anesthesiologists and the
      Belgian Scientific Society of Anaesthesia and Resuscitation, were intended to be
      fully implemented within hospital practice by January 1st, 1995. In order to
      gather follow-up data with regard to this deadline, the Professional Association
      of Anesthesiologists conducted a survey in 1995: a questionnaire was circulated
      to all Belgian anaesthetists in order to evaluate the extent to which these
      guidelines had been implemented in clinical practice and to determine the areas
      in which residual noncompliance remained. 71% of responders complied with the
      safety guidelines as far as monitoring in the operating room was concerned.
      Nursing help was available to 95% of the responders. Concerning the requirement
      for continuous attendance during anaesthesia by a doctor anaesthetist, some
      questions remain: although the principle was accepted by 53% of responders, the
      practical consequences are such that flexibility in working conditions is
      hampered by the obligation to stay at the side of the anaesthetised patient,
      under all circumstances. The survey reveals that 65% of responders do not totally
      comply with this guideline of continuous attendance by a doctor. Many of them
      propose professional assistance by nursing staff with a specific education and
      training in anaesthesia.

PMID- 11307659
TI  - Lymphedema-distichiasis and FOXC2 gene mutations.

PMID- 11307660
TI  - Lymphology in the second millennium.

PMID- 11307661
TI  - Early diagnosis of lymphedema using multiple frequency bioimpedance.
AB  - Multiple frequency bioelectrical impedance analysis (MFBIA) has previously been
      shown to provide accurate relative measures of lymphedema in the upper limb of
      patients (1). This paper reports the results of a three year prospective study to
      evaluate the efficacy of MFBIA to predict the early onset of lymphedema in
      patients following treatment for breast cancer. Bioelectrical impedance
      measurements and circumferential measurements of each upper limb were recorded in
      healthy control subjects (n = 60) to determine the normal range of the ratio
      (dominant/non-dominant) of extracellular and total limb volumes respectively.
      Patients undergoing surgery for the treatment of breast cancer were recruited as
      the study group; MFBIA and circumferential measurements were recorded pre
      surgery, one month post-surgery and then at two month intervals for 24 months.
      One hundred and two patients were recruited into the study. Twenty patients
      developed lymphedema in the 24 months follow up period of this study. In each of
      these 20 cases MFBIA predicted the onset of the condition up to 10 months before
      the condition could be clinically diagnosed. Estimates of the sensitivity and
      specificity were both approximately 100%. At the time of detection by MFBIA, only
      one of the patients returned a positive test result from the total limb volumes
      determined from the circumferential measures. These results confirmed the
      suitability of the MFBIA technique as a reliable diagnostic procedure for the
      early detection of lymphedema.

PMID- 11307662
TI  - Newly-formed lymph nodes in the submucosa in chronic inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Routine diagnostic work revealed cell aggregates reminiscent
      of lymph nodes in the bowel submucosa in occasional cases of chronic inflammatory
      bowel disease. We therefore investigated whether they fulfill criteria for
      classification as lymph nodes. METHODS: Colon with terminal ileum from a patient
      with florid Crohn's disease and a colectomy specimen from a patient with
      ulcerative colitis were investigated. Sections were immunostained with antibodies
      that recognize endothelial and sinus-lining cells, immune-accessory cells, and
      lymphoid cells. RESULTS: Circumscribed collections of cells that fulfill all the
      major criteria for classification as lymph nodes were found in the large and
      small bowel. They had marginal and intermediate sinuses (positive for BMA 120,
      CD34, CD31, X-11, and von Willebrand's factor), afferent lymph vessels, T- and B
      regions, and a capsule. Small collections composed predominantly of B cells that
      had only a marginal sinus were also occasionally observed. CONCLUSION: Secondary
      mucosa-associated lymphoid tissue, typically seen as follicular lymphoid
      hyperplasia, also appears to occur as secondary submucosal lymph nodes. This
      phenomenon seems inconsistent with the notion that lymph nodes do not develop
      after birth. We have also noted secondary development of lymph nodes in
      lymphangioma and lymphangioleiomyomatosis. It is possible that local lymph vessel
      proliferation, possibly with chronic lymphedema of the tissue involved, is an
      important prerequisite for lymph node neogenesis.

PMID- 11307663
TI  - Annular subvalvular left ventricular aneurysm associated with cardiac
      lymphostasis.

PMID- 11307664
TI  - Choosing hospice care.

PMID- 11307665
TI  - Lancaster Cleft Palate Clinic: teaming with heroes.

PMID- 11307666
TI  - The many degrees of health professionals.

PMID- 11307668
TI  - Eat Mediterranean style for good health.

PMID- 11307667
TI  - The "super germs" are here.

PMID- 11307669
TI  - The ultimate challenge. Exercise at any age.

PMID- 11307670
TI  - Can ginkgo biloba dust off mental cobwebs?

PMID- 11307671
TI  - Communicating end-of-life care.

PMID- 11307672
TI  - Stepping into Pennsylvania spring.

PMID- 11307673
TI  - Diabetes can strike at any age.

PMID- 11307674
TI  - Blast waves and how they interact with structures.
AB  - The paper defines and describes blast waves, their interaction with a structure
      and its subsequent response. Explosions generate blast waves, which need not be
      due to explosives. A blast wave consists of two parts: a shock wave and a blast
      wind. The paper explains how shock waves are formed and their basic properties.
      The physics of blast waves is non-linear and therefore non-intuitive. To
      understand how an explosion generates a blast wave a numerical modelling computer
      code, called a hydrocode has to be employed. This is briefly explained and the
      cAst Eulerian hydrocode is used to illustrate the formation and propagation of
      the blast wave generated by a 1 kg sphere of TNT explosive detonated 1 m above
      the ground. The paper concludes with a discussion of the response of a structure
      to a blast wave and shows that this response is governed by the structures
      natural frequency of vibration compared to the duration of the blast wave. The
      basic concepts introduced are illustrated in a second simulation that introduces
      two structures into the blast field of the TNT charge.

PMID- 11307675
TI  - Blast injuries: biophysics, pathophysiology and management principles.

PMID- 11307676
TI  - Small fragment wounds: biophysics, pathophysiology and principles of management.
AB  - Military surgical doctrine has traditionally taught that all ballistic wounds
      should be formally managed by surgical intervention. There is now, however, both
      experimental and clinical evidence supporting the nonoperative treatment of
      selected small fragment wounds. Low energy-transfer wounds affecting the soft
      tissues, without neuro-vascular compromise and with stable fracture patterns, may
      be suitable for early antibiotic treatment. The management of ballistic wounds to
      the gastrointestinal tract requires surgical intervention but, advances in the
      treatment of these wounds, especially those involving the colon, may allow more
      effective treatment with a reduced morbidity.

PMID- 11307677
TI  - The interaction of projectiles with tissues and the management of ballistic
      fractures.
AB  - Wounds to the limbs are the commonest injuries seen during armed conflict and
      injury results from the transfer of energy from the missile to the tissues. There
      are a number of factors that determine the transfer of energy, and thus the
      extent of wounding. These include the velocity of the missile, its shape and
      stability, and the tissue through which the missile passes. Many of the wounds
      involve bone, and because of the interaction of missiles with bone, significant
      fractures can occur. In many previous conflicts amputation was considered the
      treatment of choice for many limb injuries, but with recent advances in the
      management of severe open fractures, many of these limbs are now salvageable.
      Whilst the basic principles of the initial debridement remain unchanged,
      techniques of fracture stabilisation and definitive soft tissue cover have
      changed, and it is necessary to consider these in relation to military fractures.
      Definitive soft tissue closure can be safely delayed until evacuation further
      down the medical chain, but stabilisation of the fracture must be considered at
      the time of initial surgery. Many of the advances in fracture management may be
      unsuitable for use in a military environment due to logistical constraints. In
      addition it is likely that wound infection will be more common with military
      injuries, and this will influence the treatment. This paper considers the
      interaction of missiles with soft tissue and bone, and discusses possible methods
      of fracture stabilisation in the military environment.

PMID- 11307678
TI  - Penetrating wounds of the torso.
AB  - Penetrating trauma is on the increase as a result of interpersonal violence
      throughout the world. It is essential that military surgeons are familiar with
      such injuries and trained not only in the principles of their management, but
      also have first-hand operative experience before deployment in the field of
      conflict. More often than not, this experience is to be gained in the civilian
      urban setting in countries such as South Africa and the USA. The article
      addresses the first requirement--the principles of management--and outlines basic
      measures to enable those unfamiliar with penetrating wounds of the torso to make
      a reasonable and directed approach to dealing with these patients. It does not
      attempt to give definitive advice on specific injuries. It is organised according
      to anatomical regions, but emphasises that this is only in order to put shape to
      the article; penetrating injuries frequently having no respect for anatomical
      boundaries. Particular attention is drawn to difficult areas such as mediastinal
      injuries, and to modern concepts of 'damage control' surgery and the 'abdominal
      compartment syndrome'. The emphasis throughout is on how to get out of trouble
      and where particular danger spots may be anticipated. Reference will be made to
      the differences that may be expected within the military environment as opposed
      to the civilian setting, where rapid and (usually) safe evacuation to a well
      equipped secure facility may not be possible. The article aims to raise the
      awareness of those involved in the care of patients with penetrating wounds of
      the torso that a methodical approach with a practised team of experienced
      individuals can salvage injuries which at first sight may seem terrifying or
      hopeless.

PMID- 11307679
TI  - Combat casualties in the first decade of the 21st century--new and emerging
      weapon systems.
AB  - This paper reviews new and emerging weapons systems targeted directly or
      indirectly against personnel. It distinguishes emerging technologies that may
      form the basis of usable weapons in the next 10 years, from the speculations and
      aspirations of weapons designers, and identifies six groups of weapons systems
      which will present significant new or changing threats to UK forces. The article
      combines this information with knowledge of biophysical interactions and clinical
      effects, to identify possible consequences for the DMS in terms of types,
      patterns and numbers of casualties. Ballistic threats will continue to be the
      most common casualty-producing mechanism for servicemen in any environment.

PMID- 11307680
TI  - Anti-personnel mine injury; mechanism and medical management.

PMID- 11307681
TI  - New blast weapons.
AB  - Over the last decade a large number of weapon systems have appeared that use
      blast as their primary damage mechanism. This is a notable trend; until recently
      very few warheads relied on blast as their primary output. Most warheads in
      service use explosives to drive metal such as fragments and shaped charge jets to
      engage targets. New technologies are now being integrated into warheads that
      claim to have enhanced blast performance. Blast weapons could have been designed
      to fill a gap in capability; they are generally used for the attack of 'soft'
      targets including personnel, both in the open and within protective structures.
      With the increased number and range of these weapons, it is likely that UK forces
      will have to face them in future conflicts. This paper briefly describes fuel-air
      explosive blast weapons and reviews a range of enhanced blast weapons that have
      been developed recently. The paper concludes with a brief discussion on the
      reasons why enhanced blast technologies may be proliferating and how this could
      affect the Defence Medical Services.

PMID- 11307682
TI  - Behind armour blunt trauma--an emerging problem.
AB  - Behind Armour Blunt Trauma (BABT) is the non-penetrating injury resulting from
      the rapid deformation of armours covering the body. The deformation of the
      surface of an armour in contact with the body wall arises from the impact of a
      bullet or other projectile on its front face. The deformation is part of the
      retardation and energy absorbing process that captures the projectile. In extreme
      circumstances, the BABT may result in death, even though the projectile has not
      perforated the armour. An escalation of the available energy of bullets and the
      desire of armour designers to minimise the weight and bulk of personal armour
      systems will increase the risk of BABT in military and security forces personnel.
      In order to develop materials that can be interposed between the armour and the
      body wall to attenuate the transfer of energy into the body, it is essential that
      the mechanism of BABT is known. There is a great deal of activity within UK and
      NATO to unravel the interactions; the mechanism is likely to be a combination of
      stress (pressure) waves generated by the rapid initial motion of the rear of the
      armour, and shear deformation to viscera produced by gross deflection of the body
      wall. Physical and computer model systems are under development to characterise
      the biophysical processes and provide performance targets for materials to be
      placed between armours and the body wall in order to attenuate the injuries
      (trauma attenuating backings-TABs). The patho-physiological consequences of BABT
      are being clarified by research, but the injuries will have some of the features
      of blunt chest trauma observed in road traffic accidents and other forms of
      civilian blunt impact injury. The injuries also have characteristics of primary
      blast injury. An overview diagnosis and treatment is described.

PMID- 11307683
TI  - Burns and military clothing.
AB  - Burn injury is a ubiquitous threat in the military environment. The risks during
      combat are well recognised, but the handling of fuel, oil, munitions and other
      hot or flammable materials during peacetime deployment and training also imposes
      an inherent risk of accidental burn injury. Over the last hundred years, the burn
      threat in combat has ranged from nuclear weapons to small shoulder-launched
      missiles. Materials such as napalm and white phosphorus plainly present a risk of
      burn, but the threat extends to encompass personnel in vehicles attacked by anti
      armour weapons, large missiles, fuel-air explosives and
      detonations/conflagrations on weapons platforms such as ships. Large numbers of
      burn casualties were caused at Pearl Harbor, in Hiroshima and Nagasaki, Vietnam,
      during the Arab/Israeli Wars and in the Falkland Islands conflict. The threat
      from burns is unlikely to diminish, indeed new developments in weapons seek to
      exploit the vulnerability of the serviceman and servicewoman to burns. Clothing
      can be a barrier to some types of burn--both inherently in the properties of the
      material, but also by trapping air between clothing layers. Conversely, ignition
      of the clothing may exacerbate a burn. There is hearsay that burnt clothing
      products within a wound may complicate the clinical management, or that materials
      that melt (thermoplastic materials) should not be worn if there is a burn threat.
      This paper explores the incidence of burn injury, the mechanisms of heat transfer
      to bare skin and skin covered by materials, and the published evidence for the
      complication of wound management by materials. Even light-weight combat clothing
      can offer significant protection to skin from short duration flash burns; the
      most vulnerable areas are the parts of the body not covered--face and hands.
      Multilayered combat clothing can offer significant protection for short periods
      from engulfment by flames; lightweight tropical wear with few layers offers
      little protection. Under high heat loads in the laboratory, combat clothing can
      ignite, but there is little evidence that clothing ignition is a common
      occurrence in military burn casualties. Thermoplastic materials have many
      benefits in civil and military clothing. There is little objective evidence that
      they exacerbate burns, or complicate burn management. Their use in military
      clothing must be based on objective evidence, not hearsay.

PMID- 11307684
TI  - Asthmagenicity of coal mine roof-bolting resins: an assessment using inhalation
      provocation tests.
AB  - Inhalation provocation tests were used to assess whether the volatile products of
      an activated resin had caused occupational asthma in a non-random sample of six
      asthmatic coal miners. The resin system uses the polymerization of polyester and
      styrene under the influence of the cross-linking agent dibenzoyl peroxide to
      secure roof, wall and floor bolts in mine tunnels. The tests were conducted
      sequentially in a double-blind fashion over a 'dose' range which extended just
      beyond the maximum likely to have been experienced occupationally during a single
      day's work. The tests were monitored by symptoms, changes in the forced
      expiratory volume in 1 s (FEV1) and changes in airway responsiveness. All
      subjects completed the series of tests without any significant decrements in FEV1
      or significant increases in airway responsiveness. We conclude that the use of
      this resin system is not likely to have been the cause of the asthma in the test
      subjects, nor in the larger group of miners of which they were a sample, but
      neither possibility is fully excluded and the participants may not have been
      adequately representative of other asthmatic coal miners.

PMID- 11307685
TI  - Frequency of oral mucosa micronuclei in gas station operators after introducing
      methanol.
AB  - Methanol has been proposed in different countries as an alternative automotive
      fuel to be used as an additive to, or replacement for, gasoline or ethanol.
      Utilization of methanol is increasing exposure to low levels of methanol vapors
      in the environment and more specifically in occupational settings such as gas
      stations. Pump operators are exposed to relatively high levels of fuel vapors,
      the consequences of which have not been fully examined. In this study, the
      micronucleus assay in squamous oral cells was performed on pump operators of 28
      gas stations in three different periods in the city of Sao Paulo, Brazil. The
      frequency of micronuclei (MN) was evaluated before and 1 year after a mixed fuel
      called MEG, which contains 33% methanol, 60% ethanol and 7% gasoline, was
      introduced. The third evaluation, 3 years later, represents a period where the
      number of cars using alcohol fuel had decreased drastically and the pump operator
      exposure to MEG became very low. The frequency of MN observed in 76 employees in
      1992 (mean = 3.62 +/- 0.39) was significantly increased (P < 0.001) as compared
      with 76 operators exposed in 1989 (mean = 1.41 +/- 0.26) and 129 exposed in 1995
      (mean = 1.20 +/- 0.15). These differences were also significant when compared
      with control groups not exposed professionally to motor fuel. These findings
      could indicate a mutagenic hazard of the MEG occurring in those with occupational
      exposure.

PMID- 11307686
TI  - Tetanus in a central Italian region: scope for more effective prevention among
      unvaccinated agricultural workers.
AB  - In 1997, Italy had the highest number of tetanus cases in the European Union;
      cases in the Marches region were more numerous than in France or Germany. In a
      retrospective study of the patients infected in Marches in 1996-1999, subjects or
      relatives were interviewed to ascertain disease severity, infection mode,
      occupation and immunization state at the time of infection. There were 32 cases,
      29 (90.6%) females and three (9.4%) males, mean age 74.65 years (SD 9.06). The
      raw annual incidence was 5.6 per million and raw annual mortality 0.5 (n = 3).
      Twenty-seven patients (84.4%) were agricultural workers and five (15.6%)
      housewives; 25 (78.2%) had never been vaccinated, two (6.2%) had been immunized
      several years earlier and five (15.6%) had received only the first dose of
      vaccine at least 15 years earlier. In Italy, tetanus vaccination is compulsory
      for agricultural workers. Occupational health physicians should monitor workers'
      tetanus immunization state during their periodic surveillance visits.

PMID- 11307687
TI  - The design of hazard risk assessment matrices for ranking occupational health
      risks and their application in mining and minerals processing.
AB  - Two hazard risk assessment matrices for the ranking of occupational health risks
      are described. The qualitative matrix uses qualitative measures of probability
      and consequence to determine risk assessment codes for hazard-disease
      combinations. A walk-through survey of an underground metalliferous mine and
      concentrator is used to demonstrate how the qualitative matrix can be applied to
      determine priorities for the control of occupational health hazards. The semi
      quantitative matrix uses attributable risk as a quantitative measure of
      probability and uses qualitative measures of consequence. A practical application
      of this matrix is the determination of occupational health priorities using
      existing epidemiological studies. Calculated attributable risks from
      epidemiological studies of hazard-disease combinations in mining and minerals
      processing are used as examples. These historic response data do not reflect the
      risks associated with current exposures. A method using current exposure data,
      known exposure-response relationships and the semi-quantitative matrix is
      proposed for more accurate and current risk rankings.

PMID- 11307688
TI  - Occupational health guidelines for the management of low back pain at work:
      evidence review.
AB  - There is increasing demand for evidence-based health care. Back pain is one of
      the most common and difficult occupational health problems, but there has been no
      readily available evidence base or guidance on management. There are well
      established clinical guidelines for the management of low back pain, but these
      provide limited guidance on the occupational aspects. Occupational Health
      Guidelines for the Management of Low Back Pain at Work were launched by the
      Faculty of Occupational Medicine in March 2000. These are the first national
      occupational health guidelines in the UK and, as far as we are aware, the first
      truly evidence-linked occupational health guidelines for back pain in the world.
      They were based on an extensive, systematic review of the scientific literature
      predominantly from occupational settings or concerning occupational outcomes. The
      full evidence review is on the Faculty web site (www.facoccmed.ac.uk), but an
      abridged version is presented here to aid its dissemination.

PMID- 11307689
TI  - Severe headache associated with occupational exposure to Stoddard solvent.
AB  - We report a case of recurrent headaches in a woman with a workplace exposure to
      airborne (misted) lubricating fluid containing Stoddard solvent. For 2 months,
      the employee was seen by her family physician, a neurologist and an
      ophthalmologist. All attempted to diagnose the cause of and treat her headaches.
      Despite extensive testing, no etiology was discovered. Her headaches continued
      despite the use of medications. The employee, suspecting an occupational
      connection, changed the lubricating fluid at her workstation to a non-Stoddard
      solvent. Within 2 days she reported the complete resolution of her headaches with
      no further recurrences. A thorough occupational history and literature review
      supported exposure to Stoddard solvent as the probable source of her headaches.

PMID- 11307690
TI  - Idiopathic central serous chorioretinopathy--a physical complication of stress?
AB  - The adverse psychological sequelae of stress are well recognized by occupational
      health specialists. Potential adverse physical effects, such as ischaemic heart
      disease, are more contentious but are biologically plausible. This report
      outlines a case of idiopathic central serous chorioretinopathy (ICSC), an
      uncommon but potentially sight-threatening condition, which is widely accepted
      amongst ophthalmologists to be stress related. The condition is not referred to
      in standard occupational health texts or databases. The report includes a brief
      review of the ophthalmological literature on which the connection between ICSC
      and stress has been made, and a need for further research promoted.

PMID- 11307691
TI  - Respiratory symptoms and wheat flour exposure: a study of flour millers.

PMID- 11307692
TI  - Developing evidence-based guidelines in occupational health.

PMID- 11307693
TI  - The analysis of sensitivity, specificity, positive predictive value and negative
      predictive value of cold provocation thermography in the objective diagnosis of
      the hand-arm vibration syndrome.
AB  - The diagnosis of digital artery vasospasm in the hand-arm vibration syndrome
      (HAVS) is clinically based, and the need for an accurate objective test to
      support the diagnosis has been highlighted. This study aims to analyse the
      potential of cold provocation thermography (CPT) to fulfill this role. CPT was
      performed on two groups of subjects: 10 controls and 21 patients with Raynaud's
      phenomenon (RP) secondary to HAVS. After taking a pre-cooling image, patients
      donned latex gloves and immersed their hands in water at a temperature of 5
      degrees C for 1 min. The patients removed their hands from the water and
      discarded the gloves, and further images were taken every 30 s for 10 min. On
      each image, the temperatures of the tip and base were analysed for each digit.
      The sensitivity, specificity, positive and negative predictive values for
      fingertip temperatures only, fingertip and fingerbase temperatures combined, and
      fingertip temperature, fingerbase temperature and temperature gradient combined
      were determined. Patients with RP secondary to HAVS demonstrated significantly
      lower finger tip and base temperatures and lower digital temperature gradients at
      all time intervals when compared with controls (P < 0.01, Student's t-test). CPT
      has good sensitivity, specificity, positive predictive value and negative
      predictive value; it strongly supports the clinical diagnosis of digital
      vasospasm.

PMID- 11307694
TI  - Current best practice for the health surveillance of enzyme workers in the soap
      and detergent industry.
AB  - This study defines current best practice for the health surveillance of workers
      who are potentially exposed to enzymes in the manufacture of enzymatic detergent
      products. It is recommended that health surveillance is performed 6-monthly for
      the first 2 years and annually thereafter. The health surveillance programme
      should include a respiratory questionnaire to detect symptoms, assessment of lung
      function to detect pre-symptomatic changes and an immunological test to detect
      specific immunoglobulin E (IgE) to enzymes. The International Union Against
      Tuberculosis and Lung Disease respiratory questionnaire should be used since it
      has been validated extensively for detecting asthma. Operators should observe the
      American Thoracic Society performance criteria for spirometers and standardized
      procedures for conducting spirometry. Since current airborne monitoring
      techniques for enzymes do not detect short-duration peak exposures, the incidence
      of employee sensitizations remains the most reliable measure of the integrity of
      environmental control. The Pepys skin prick test has been validated as a
      sensitive, specific and practical test for detecting specific IgE to many
      inhalant allergens including enzymes. For newly sensitized workers, a multi-cause
      investigation should be conducted to identify potential sources of exposure.
      Group results of immunological test results assist in the evaluation of workplace
      control measures, and should be used to monitor the effectiveness of hygiene and
      engineering programmes and to help prioritize areas for improvement. Positive
      responses to a questionnaire or abnormal spirometry should be assessed further.
      Occupational asthma should be excluded in any case of adult-onset asthma that
      starts or deteriorates during working life. This is particularly important
      because an accurate diagnosis of occupational asthma with early avoidance of
      exposure to its cause can result in remission of symptoms and restoration of lung
      function.

PMID- 11307695
TI  - A special courage: dealing with the Paddington rail crash.
AB  - Supporting traumatized employees requires special skills and techniques if it is
      to be effective. Unfortunately, there is little to inform or guide organizations
      on how this should be achieved. The present controversy over the use of trauma
      management systems and debriefing has not been helpful in informing organizations
      on the best way to take care of employees who become traumatized during the
      course of their work. This paper looks at how Sainsbury's Supermarkets Ltd
      managed traumatization through the activation of its Violence at Work policy and
      procedures, and finally presents the results of an evaluation exercise that was
      undertaken following the Paddington rail crash.

PMID- 11307696
TI  - His mother-tongue: from stuttering to separation, a case history.
AB  - This paper delineates the transference and countertransference experiences in the
      analysis of a patient whose presenting symptom and main concern was his stutter.
      I suggest that oral-sadistic rather than anal-sadistic hostile elements may be
      identified in this patient's particular stutter. I focus on its significance in
      terms of object relationship: my patient's struggle to 'get born', to emerge as a
      separate other. I argue that early symbiotic fusion needs in conflict with the
      need to separate produce his stutter. Speech and language are seen as the vehicle
      for separation and the stutter as a flight from separateness back to an illusion
      of fusion with mother.

PMID- 11307697
TI  - Enactments and amplification.
AB  - Advances in the understanding and articulation of enactments allow a reassessment
      of analytical psychology's method of amplification. Subjective and objective
      aspects of the amplificatory process, evolving notions of its role in analysis
      together with the use of countertransference phenomena provide the frame for
      reexamination of this method. Using a single analytic day, this paper explores
      the inevitable play of enactments with a focus on countertransferential
      components contained in the act of amplification. An internal examination of such
      an act is used to attempt to identify and differentiate the operative personal,
      interpersonal and collective aspects. The impact and traces of this act are
      followed through the workings of the day and demonstrate that the impulse to
      amplify is a suitable object for analytic scrutiny. This leads to a more general
      question of the mythic nature of enactments.

PMID- 11307698
TI  - Archetypes, complexes and self-organization.
AB  - There has always been confusion and disagreement about the nature of the terms
      archetype and complex in Jungian circles, not to mention non-Jungian ones.
      Another ongoing concern is whether Jung's concept of the archetype and complex
      can be justified in terms of current scientific research, most notably that of
      neurophysiologists and others interested in the brain and consciousness. This
      paper proposes a theory of the formation of complexes, namely, that they are
      created through self-organization within the brain/mind. Self-organization is a
      process typical of large complex systems, and is generally accepted to operate
      within the brain and to be important in its functioning. Examples of self
      organization in biology are related to the psychic processes that form the
      complexes. It is then natural to define the archetype in terms of the complex,
      and the authors propose a definition of the archetype as an equivalence class of
      complexes. On this view, the archetype is an emergent property of the activity of
      the brain/mind, and is, appropriately, defined at the level at which it emerges.
      This definition is in line with the original development of Jung's ideas, in that
      he derived the concept of the archetype from his earlier discovery of the feeling
      toned complex.

PMID- 11307699
TI  - The future of analysis.
AB  - The aim of analysis is to enable our patients to differentiate themselves from
      their past. The question we face as analysts is whether we are in fact
      neurotically bound to repeat the past. This paper addresses this question by
      considering some of the reasons that there is a 'crisis in analysis'. Two central
      problems within the practice of analysis are identified as contributing to this
      'crisis': 1) a view of the patient as 'enemy', or as innately destructive; and 2)
      a trend towards here-and-now interpretations within the transference which
      disregards history and the role of external reality. The danger of such an
      approach is that it does not allow patients to separate from their hateful primal
      scenes and to become free of neurotic guilt. When we are anxious about our own
      destructiveness and aggression and do not link this to a failure to form a loving
      relation, we run the risk of fostering compliance and conformity within our
      patients and within our own professional societies. In contrast, it is the
      recognition of the past and its influence on the present that makes analysis a
      tool for revolution.

PMID- 11307700
TI  - Institutional conflicts in Jungian analysis.
AB  - This paper explores how the institutional life of analytical psychology has been
      beset by its historical and continuing conflictual relationship with
      psychoanalysis. Stemming from a division in Jung's identity, that of the
      spiritual seeker and that of a mental health practitioner, the organizations of
      analytical psychology have repeatedly enacted that division, resulting in an
      unclear mission and considerable conflict. In England those conflicts have led to
      schisms; in America they have played out in internal conflicts within training
      institutes. Examples of areas of conflict are provided, along with suggestions
      for addressing these conflicts by recognizing them more openly.

PMID- 11307701
TI  - What is our age suffering from? The Schweizer Illustrierte interviews the well
      known psychiatrist Prof. Dr C. G. Jung. (August 12, 1942).

PMID- 11307702
TI  - A lecture by Barbara Hannah as recalled by David Lindorff.

PMID- 11307703
TI  - The role of scaffolding errors in reading development: evidence from a
      longitudinal and a correlational study.
AB  - BACKGROUND: Identification of patterns of early reading behaviour that predict
      later reading success is clearly important. Reading errors of 6-year-olds
      represent a source of such early assessment information, but their significance
      as predictors of later reading is unknown. AIMS: The relationship between word
      reading errors at age 6 and accurate word reading at age 8 is investigated here.
      SAMPLES, METHODS, RESULTS: In study 1, 44 children completed word reading tests
      at 6 and 8 years. 'Scaffolding errors' preserving both initial and final phonemes
      (e.g., 'bark' misread as 'bank'); errors preserving either initial or final
      phonemes (e.g., 'bark' misread as 'bed' or 'like'); distant or unrelated errors
      (e.g., 'bark' misread as 'can' or 'men') and non-responses were measured at age
      6. Scaffolding errors were the best predictors of word reading at age 8. Study 2
      investigated the correlations between word and nonsense word reading, and
      scaffolding errors in 30 children aged 6 years. Scaffolding errors predicted
      unique variance in word reading after nonword reading was entered. CONCLUSIONS:
      Scaffolding errors represent a significant qualitative indicator of later word
      reading success. Implications of findings for early identification of reading
      difficulties, and facilitating reading interventions are discussed.

PMID- 11307704
TI  - Approaches to learning in science: a longitudinal study.
AB  - BACKGROUND: Longitudinal studies of students' approaches to learning in higher
      education can tell us much about the impact of the tertiary experience. More
      information about teaching and learning practices and how students respond to
      these may enable educators to better assist students to gain the maximum benefit
      from their tertiary studies. AIMS: The study set out: (i) to monitor the change
      in approaches to learning over a three-year period; (ii) to evaluate the
      relationship between student age, sex and university entry mode on students'
      approaches to learning; and (iii) to evaluate the predictive validity of the SPQ
      scales on one mode of learning outcome, that being annual GPA. SAMPLES: The
      sample consisted of 200 commencing students studying in a science course at an
      Australian university. METHOD: The Biggs SPQ was administered in a first-year
      chemistry class and repeated at intervals of 4 and 8 months. This was followed by
      administration by post after 16 months and 30 months. RESULTS: Student approach
      to learning is dynamic and amenable to change as a result of the learning
      experience. Of the three SPQ scales, the achieving approach appears to undergo
      the greatest change with time, while the deep approach showed a consistent
      positive correlation with assessment outcomes. Student age was a major factor in
      both the SPQ scores and assessment outcomes but no gender effect was evident.
      CONCLUSIONS: Students see university study, and in particular the first year, as
      a survival course and adopt strategies suited to that task. Older students adopt
      approaches to study which differ from their younger colleagues and as a
      consequence they are in general more successful in the tertiary environment.

PMID- 11307705
TI  - The revised two-factor Study Process Questionnaire: R-SPQ-2F.
AB  - AIM: To produce a revised two-factor version of the Study Process Questionnaire
      (R-SPQ-2F) suitable for use by teachers in evaluating the learning approaches of
      their students. The revised instrument assesses deep and surface approaches only,
      using fewer items. METHOD: A set of 43 items was drawn up for the initial tests.
      These were derived from: the original version of the SPQ, modified items from the
      SPQ, and new items. A process of testing and refinement eventuated in deep and
      surface motive and strategy scales each with 5 items, 10 items per approach
      score. The final version was tested using reliability procedures and confirmatory
      factor analysis. SAMPLE: The sample for the testing and refinement process
      consisted of 229 students from the health sciences faculty of a university in
      Hong Kong. A fresh sample of 495 undergraduate students from a variety of
      departments of the same university was used for the test of the final version.
      RESULTS: The final version of the questionnaire had acceptable Cronbach alpha
      values for scale reliability. Confirmatory factor analysis indicated a good fit
      to the intended two-factor structure. Both deep and surface approach scales had
      well identified motive and strategy subscales. CONCLUSION: The revision process
      has resulted in a simple questionnaire which teachers can use to evaluate their
      own teaching and the learning approaches of their students.

PMID- 11307706
TI  - How to make it easier for children to revise their writing: a study of text
      revision from 3rd to 5th grades.
AB  - BACKGROUND: Writing is considered as a complex activity, involving at least three
      processes: planning, translating and revising. The experiment proposed here
      focused on this last process, from a developmental perspective. AIMS: The
      objective of this study was to examine if a delay between writing and revising
      could improve the frequency and the nature of revisions. In two out of three
      writing sessions the revising period was delayed to lighten the cognitive load
      associated with the revising process. The main hypothesis was that the revisions
      would be more frequent in older children's texts and during the sessions in which
      the revising process was delayed. SAMPLE: Sixty children (20 per grade) from 3rd
      to 5th grades participated in the study. METHOD: These children were asked to
      write a text, and to revise it, when the revising phase occurred, whether during
      the writing phase or afterwards. RESULTS: The text length, the frequency of
      errors and the frequency and the nature of revisions were analysed. The main
      results showed that, surprisingly, 3rd graders produced shorter texts, containing
      more errors, but revised more than 4th and 5th graders. The two postponed
      revising conditions led to more revisions than the revision occurring during
      writing. Surface revisions were more frequent than meaning revisions, but this
      result was only significant for younger children, or when revision occurred
      during writing. For all grades and revising conditions, surface revisions were
      mainly script and spelling corrections; meaning revisions were mainly additions
      and deletions of words or parts of texts. CONCLUSION: This study shows the effect
      of children's grade on revision, and that postponing the revising process seems
      to help children to increase the frequency and the depth of their revisions.

PMID- 11307707
TI  - Self-handicapping status, claimed self-handicaps and reduced practice effort
      following success and failure feedback.
AB  - BACKGROUND: Self-handicapping involves the strategic establishment of an
      impediment or obstacle to success prior to a performance situation which thereby
      provides a convenient excuse for poor performance. AIMS: The study sought to
      establish that relative to low trait self-handicappers, high trait self
      handicappers exposed to failure in an intellectually evaluative situation will
      (a) pre-emptively claim more handicaps, and (b) behaviourally self-handicap
      through reduced practice effort, and (c) report greater anxiety and negative
      affect relative to low trait self-handicappers. SAMPLE: Participants were 72
      undergraduate students, divided equally between high and low self-handicapping
      groups. METHOD: This study utilised a 2 (self-handicapping status: high, low) x 3
      (performance feedback: fail, low task importance; fail, high task importance;
      success) between-subjects factorial design to investigate claimed and behavioural
      self-handicapping through reduced practice effort. This was done by manipulating
      performance outcome and perceived task importance. RESULTS: Relative to low trait
      self-handicappers, high trait high self-handicappers claimed more handicaps and
      engaged in greater behavioural self-handicapping following failure when working
      on tasks that were described as potentially diagnostic of low ability. While low
      self-handicappers internalised their success more than their failure in the high
      task importance condition, high self-handicappers were undifferentiated in their
      attributions across performance conditions. Greater anxiety and greater negative
      affect were also characteristic of high self-handicappers. CONCLUSIONS: The study
      highlights the self-protective benefit of self-handicapping in sparing the
      individual from conclusions of low ability, and the failure of high self
      handicappers to fully internalise their success. These elements and the role of
      uncertain estimates of ability are discussed in considering implications for
      intervention.

PMID- 11307708
TI  - Inattention, hyperactivity and impulsiveness: their impact on academic
      achievement and progress.
AB  - BACKGROUND: Children with Attention Deficit Hyperactivity Disorder (ADHD) have
      been found to achieve lower grades at school than their peers. Does this extend
      to pupils who are apparently exceptionally inattentive, hyperactive or impulsive,
      but have not been diagnosed as having ADHD? AIMS: This study determined the
      proportion of children who were assessed by their teachers as exceptionally
      inattentive, hyperactive or impulsive in the classroom. The relationships between
      these traits, achievement and progress were examined. SAMPLE: The participants
      comprised 4148 children from a nationally representative sample of schools in
      England. METHODS: Reading and mathematics achievement of the participants was
      assessed at the start and end of the reception year, and in year 2. Behaviour was
      assessed at the end of reception using a rating scale based on the diagnostic
      criteria for ADHD (American Psychiatric Association, 1994). RESULTS: The
      proportion of children with exceptional scores on the behaviour rating scale was
      reported. The reading and mathematics attainment and value-added of children with
      high scores on the behaviour rating scale were found to be educationally and
      statistically significantly lower than children with zero scores. CONCLUSIONS:
      The achievement of children with high scores on the behaviour rating scale
      replicated previous studies which investigated the achievement of children with
      ADHD. The behaviour rating scale could be a useful tool for raising the awareness
      of teachers to young children with severe behavioural problems of inattention,
      hyperactivity and impulsivity who have not been diagnosed as having ADHD but may
      nevertheless be at risk of similar outcomes.

PMID- 11307709
TI  - Student teachers' beliefs about mentoring and learning to teach during teaching
      practice.
AB  - BACKGROUND: Various interpretations of mentor roles, by teacher educators and
      mentors, have been described in the literature on mentoring, while those of
      student teachers have received less attention. Therefore, this study focuses on
      student teachers' expectations of mentors and their own contributions to their
      learning process while they are supervised by a mentor. AIMS: The main aims of
      this study were: (1) bridging the research on mentoring and the research on
      higher education students' learning conceptions by investigating student
      teachers' beliefs about mentoring and learning to teach, and (2) comparing these
      beliefs to mentors' ones and recent views on mentoring and learning in order to
      make suggestions for improving learning to teach. SAMPLE: Thirty student
      teachers, graduates in various academic disciplines, participated. They were
      attending a one-year teacher education programme at Leiden University in the
      Netherlands. METHODS: Structured interviews with the student teachers were audio
      taped. Firstly, categories of mentor roles and learning activities were derived
      from the data. These were linked, secondly, by their focus of attention and,
      thirdly, empirically by a homogeneity analysis (HOMALS). RESULTS: Six mentor
      roles, ten learning activities, and one regulation activity were combined in six
      foci: (1) affective aspects of learning to teach, (2) mentors' teaching styles,
      (3) assessment of student teachers' performance, (4) reflecting on students'
      lessons, (5) school context, and (6) self-regulation of learning. The HOMALS
      analysis yielded a process-product dimension. CONCLUSION: In this study, the
      student teachers' beliefs about mentoring were similar to those of mentors.
      Furthermore, a third of the student teachers expected themselves as thinking
      critically about their lessons, but nobody expected their mentors to explicate
      their practical knowledge underlying their teaching. Therefore, the articulation
      of this knowledge is indicated as an additional mentor role and will be
      elaborated.

PMID- 11307710
TI  - The relationship of work avoidance and learning goals to perceived competence,
      externality and meaning.
AB  - BACKGROUND: Motivational researchers have suggested that work avoidance may be an
      academic goal in which students seek to minimise the amount of work they do in
      school. Additionally, research has also suggested that emotions may be catalysts
      for goals. AIM: This study examined the relationship between emotions and
      learning or work avoidance goals. Do emotions explain goals? SAMPLE: The
      participants were 512 senior high school students in Eastern Canada. METHOD:
      Students completed a survey assessing motivation related constructs. A structural
      equation model was postulated in which students' affect predicted learning goals
      and work avoidant goals. A cluster analysis of affect scores was performed
      followed by between-group and within-group contrasts of goal scores. RESULTS: The
      structural equation model suggested that a sense of competence and control were
      predictive of a learning goal while lack of meaning was related to work
      avoidance. The cluster analysis showed that confidence and control were
      associated with a learning goal but that a sense of inadequacy, lack of control
      or lack of meaning could give rise to work avoidance. CONCLUSIONS: Emotions seem
      to be directly linked to goals. Teachers who foster feelings of self-assuredness
      will be helping students develop learning goals. Students who feel less
      competent, bored or have little control will adopt work avoidant goals.

PMID- 11307711
TI  - The predictive and discriminant validity of the zone of proximal development.
AB  - BACKGROUND: Dynamic measurement procedures are supposed to uncover the zone of
      proximal development and to increase predictive validity in comparison to
      conventional, static measurement procedures. AIMS: Two alternative explanations
      for the discrepancies between static and dynamic measurements were investigated.
      The first focuses on Vygotsky's learning potential theory, the second considers
      the role of anxiety tendency during test taking. If test anxious tendencies are
      mitigated by dynamic testing procedures, in particular the availability of
      assistance, the concept of the zone of proximal development may be superfluous in
      explaining the differences between the outcomes of static and dynamic
      measurement. SAMPLE: Participants were students from secondary education in the
      Netherlands. They were tested repeatedly in grade three as well as in grade four.
      Participants were between 14 and 17 years old; their average age was 15.4 years
      with a standard deviation of .52. METHOD: Two types of mathematics tests were
      used in a longitudinal experiment. The first type of test consisted of open-ended
      items, which participants had to solve completely on their own. With the second
      type of test, assistance was available to participants during the test. The
      latter so-called learning test was conceived of as a dynamic testing procedure.
      Furthermore, a test anxiety questionnaire was administered repeatedly. Structural
      equation modelling was used to analyse the data. RESULTS: Apart from emotionality
      and worry, lack of self-confidence appears to be an important constituent of test
      anxiety. The learning test appears to contribute to the predictive validity of
      conventional tests and thus a part of Vygotsky's claims were substantiated.
      Moreover, the mere inclusion of a test anxiety factor into an explanatory model
      for the gathered data is not sufficient. Apart from test anxiety and mathematical
      ability it is necessary to assume a factor which may be construed as mathematics
      learning potential. CONCLUSION: The results indicate that the observed
      differences between a conventional, static testing procedure and an experimental,
      dynamic testing procedure for mathematics cannot be explained sufficiently by a
      differential bias towards test anxiety. The dynamic testing approach renders
      scores which add to the predictive validity of conventional testing procedures.
      Since this gain in predictive validity is not a result of the removal of bias
      towards test anxiety, this result should be understood as supportive for the
      validity of the concept of the zone of proximal development.

PMID- 11307712
TI  - Neuroimmunomodulation: perspectives at the new millennium. Proceedings of the 4th
      International Congress of the International Society for Neuroimmunomodulation.
      September 29-October 2, 1999. Lugano, Switzerland.

PMID- 11307713
TI  - [Pathology 2000 Meeting. 11-15 December 2000. Paris, France. Proceedings and
      abstracts].

PMID- 11307714
TI  - Hypermutation in antibody genes. Papers of a discussion meeting. 5-6 July 2000.

PMID- 11307715
TI  - Proceedings of a conference on setting the agenda for rural women's health.

PMID- 11307716
TI  - [Consensus conference on the management of infant bronchiolitis. Paris, France,
      21 September 2000. Proceedings].

PMID- 11307717
TI  - 10th Winternational Symposium of the Canadian Society of Biochemistry and
      Molecular and Cellular Biology: Genes and Development. Banff, Alberta, Canada.
      March 2-5, 2000. Proceedings and abstracts.

PMID- 11307719
TI  - Annual Clinical Genetics Meeting. March 19-21, 1999. Miami, Florida, USA.
      Abstracts.

PMID- 11307718
TI  - Proceedings of the ECPI World Vaccine Congress. Geneva, Switzerland, 27-29
      September 1999.

PMID- 11307720
TI  - [Trends in clinical neurology research. Annual meeting of the French Society of
      Neurology. Paris, France, 11 January 2001. Abstracts].

PMID- 11307722
TI  - Canadian Digestive Diseases Week. February 21-28, 2001. Banff, Alberta, Canada.
      Abstracts.

PMID- 11307723
TI  - Abstracts of the 70th Annual Meeting of the American Association of Physical
      Anthropologists. Kansas City, Missouri, USA. March 28-31, 2001.

PMID- 11307721
TI  - The European registry of cardiac catheter interventions 1996.

PMID- 11307724
TI  - Abstracts of meetings of the European Association for Endoscopic Surgery, the
      Association of Endoscopic Surgeons of Great Britain and Ireland, and the Society
      of American Gastrointestinal and Endoscopic Surgeons. 1999-2001.

PMID- 11307725
TI  - [82nd Congress of the Association of Morphologists. 1-3 June 2000. Dijon, France.
      Abstracts].

PMID- 11307726
TI  - [Association of Morphologists. Membership list].

PMID- 11307727
TI  - American Urogynecologic Society 21st Annual Scientific Meeting. October 25-28,
      2000. Hilton Head, South Carolina, USA. Abstracts.

PMID- 11307728
TI  - Tracheal intubation: training and retention.

PMID- 11307729
TI  - Radial arterial lines and sticks: what are the risks?

PMID- 11307730
TI  - Dual control modes, closed loop ventilation, handguns, and tequila.

PMID- 11307731
TI  - Innovations in mechanical ventilation: what are (and what should be) the drivers?
      The Roger C. Bone Memorial Lecture.

PMID- 11307732
TI  - Device evaluation: a critique.

PMID- 11307733
TI  - Allen's test: fact or myth?

PMID- 11307734
TI  - Aerosols and the profession of respiratory care: leading the way out of the fog.

PMID- 11307735
TI  - The lack of data on off-label use of noninvasive positive pressure ventilation in
      children.

PMID- 11307736
TI  - Recent Advances on the Nutritional Effects Associated with the Use of Garlic as a
      Supplement. November 15-17, 1998. Newport Beach, California, USA. Proceedings.

PMID- 11307737
TI  - Do we need controlled clinical trials in pulmonary arterial hypertension?

PMID- 11307738
TI  - In vitro assessment of equipment and software to assess tidal breathing
      parameters in infants.
AB  - The aim of this in vitro study was to compare the measurement accuracy of two
      currently available devices for measuring tidal breathing in infants. A
      mechanical model pump was used to generate flow profiles which simulated those
      observed in infants. A range of flows was applied simultaneously to two different
      devices, namely the commercially available SensorMedics 2600 (SM 2600) and more
      recently developed, custom-made equipment based on the flow-through technique
      (FTT). Automatically derived values from both devices were compared with one
      another and with manual calculations of printouts of the same breaths. There were
      no differences in the raw flow signal obtained from the two devices, nor between
      values calculated automatically or manually from the FTT. Similarly, the
      deviations between the FTT and SM 2600 were <3% for tidal volume, respiratory
      frequency and minute ventilation. However, when comparing either with manually
      calculated values or those derived automatically from the FTT, there was a
      systematic and highly significant underestimation of shape-dependent parameters,
      such as the time to peak tidal expiratory flow as a proportion of tidal
      expiratory time (tPTEF/tE), derived by the SM 2600. The lower the applied flow,
      the higher the observed deviations, the underestimation being up to 60% when
      flows simulating those observed in preterm neonates were applied. These errors
      appear to result from differences in signal processing such as the algorithms
      used for breath detection and can only be detected if appropriate nonsinusoidal
      flow profiles representing those seen in infants are used to evaluate equipment.

PMID- 11307739
TI  - Effect of apparatus dead space on breathing parameters in newborns: "flow
      through" versus conventional techniques.
AB  - Commercial devices for tidal breathing measurements in newborns allow only short
      term measurements, due to the high apparatus dead space of the face mask and
      pneumotachometer. The flow-through technique (FTT) minimizes the dead space by a
      background flow, thereby allowing long-term measurements. The aim of this study
      was to investigate the comparability of tidal breathing parameters using both
      techniques. Paired measurements of tidal breathing were performed in 86 sleeping
      infants (median (range) body weight 2.8 kg (1.9-5.3 kg), age 65 days (3-150
      days)), using the FTT and SensorMedics 2600 (SM 2600). There was a significant
      bias (p <0.001) in all tidal breathing parameters. Compared with the FTT,
      increases (95% confidence interval (CI)) in tidal volume (VT), respiratory
      frequency (fR), and minute ventilation (V'E) were 0.74 (0.5-1.0) mL.kg(-1), 9.0
      (6.9-11.2).min(-1) and 92 (74-109) mL.min(-1).kg(-1) when measured with the SM
      2600, representing average increases of 13, 17 and 30%, respectively, in response
      to the added dead space. By contrast, time to peak tidal expiratory flow as a
      proportion of expiratory time (tPTEF/tE) was changed by -0.09 (-0.11-0.08). The
      mean (95% CI) change in tPTEF/tE of -54 (-62-45)%, when measured in infants by
      the SM 2600, was remarkably similar to that observed during in vitro validation
      studies (-59 (-73-44)%), suggesting that the discrepancies in timing parameters
      may be largely attributable to differences in signal processing. In conclusion,
      differences in measurement technique and precision of the devices used can result
      in significant differences in tidal breathing parameters. This may impede the
      comparison of results within and between infants and the clinical interpretation
      of tidal breathing measurements in newborns.

PMID- 11307740
TI  - Dynamic respiratory system mechanics in infants during pressure and volume
      controlled ventilation.
AB  - Dynamic respiratory system mechanics can be determined using multiple linear
      regression (MLR) analysis. There is no need for a particular ventilator setting
      or for a special ventilatory manoeuvre. The purpose of this study was to
      investigate whether or not different ventilator modes and the flow-dependent
      resistance of the endotracheal tube (ETT) influence the determination of
      resistance and compliance by MLR. Ten paediatric patients who were on controlled
      mechanical ventilation for various disorders were investigated. The ventilator
      modes were changed between pressure control (PC) and volume control (VC). Flow
      and airway pressure were measured and tracheal pressure was continuously
      calculated. Each mode was applied for 3 min, and 10 consecutive breaths at the
      end of each period were analysed. Respiratory mechanics were determined by MLR
      based on either airway pressure, thus including the resistance of the ETT, or
      tracheal pressure. Resistance was found to be slightly higher in PC than in VC.
      There was no effect on determination of compliance between the different modes.
      Elimination of the flow-dependent resistance of the ETT preserved the differences
      between the modes. The authors conclude that using multiple linear regression
      compliance is not affected by the actual ventilator mode, whereas resistance is.

PMID- 11307741
TI  - Smoking-related interstitial lung diseases: a concise review.
AB  - Interstitial lung diseases (also known as diffuse infiltrative lung diseases) are
      a heterogeneous group of parenchymal lung disorders of known or unknown cause.
      These disorders are usually associated with dyspnoea, diffuse lung infiltrates,
      and impaired gas exchange. The majority of interstitial lung diseases are of
      unknown cause. Known causes of interstitial lung disease include inhalation of
      organic and inorganic dusts as well as gases or fumes, drugs, radiation, and
      infections. This review summarizes the clinical, radiological, and
      histopathological features of four interstitial lung disorders that have been
      linked to smoking. These disorders include desquamative interstitial pneumonia,
      respiratory bronchiolitis-associated interstitial lung disease, pulmonary
      Langerhans' cell histiocytosis, and idiopathic pulmonary fibrosis. Available
      evidence suggests most cases of desquamative interstitial pneumonia, respiratory
      bronchiolitis-associated interstitial lung disease, and pulmonary Langerhans'
      cell histiocytosis are caused by cigarette smoking in susceptible individuals.
      Smoking cessation should be a main component in the initial therapeutic approach
      to smokers with these interstitial lung diseases. In addition, smoking appears to
      be a risk factor for the development of idiopathic pulmonary fibrosis.

PMID- 11307742
TI  - Fungal infections in transplant recipients.
AB  - Fungi are ubiquitous and the respiratory tract is exposed to aerosolized spores
      of both fungi that are "pathogenic" even in the normal host, such as Cryptococus
      neoformans, and those that are "opportunistic", such as Candida and Aspergillus
      species, among others. Although these latter species may occasionally form fungal
      balls or induce allergic phenomena in the normal host, they produce more invasive
      diseases in immunosuppressed patients. Among these diseases, pseudomembranous
      aspergillosis has recently been described. The diagnostic approach to these
      entities, and, in particular, the thin dividing line between colonization and
      infection are addressed, along with the diagnostic value of the various
      procedures. New prophylactic regimens are reviewed such as the possibility of
      using amphotericin aerosols in combination with systemic azole administration.
      The authors would emphasize the importance of restoring lung defences by not only
      decreasing immunosuppressive regimens but also considering the use of newly
      available recombinant cytokines such as growth factors, to reduce neutropenia,
      for instance, in addition to antifungal drugs when infection is diagnosed.
      However, immunomodulation procedures are far from being well established.

PMID- 11307743
TI  - Ultrasonic versus jet nebulization of iloprost in severe pulmonary hypertension.
AB  - Inhalation of iloprost, a stable prostacyclin analogue, is a promising
      perspective in the treatment of pulmonary hypertension. In initial clinical
      studies, a conventional jet nebulizer system was successfully used to decrease
      pulmonary vascular resistance and pressure, requiring however, up to twelve
      inhalations of 12-15 min per day. The aim of this study was to investigate if the
      application of an equal dose of iloprost at a drastically reduced duration of
      inhalation with the use of a more efficient ultrasonic nebulizer, leads to
      comparable haemodynamic effects, without escalation of side effects. The physical
      features of the jet nebulizer system (Ilo-Neb) and the ultrasonic nebulizer
      (Multisonic Compact) were characterized by laser diffractometry and a Tc99m
      tracer technique. Mass median aerodynamic diameters were 3.2 microm for the jet
      and 3.9 microm for the ultrasonic nebulizer. Total output (mean+/-SD) was 60+/-7
      microL.min(-1) (jet) and 163+/-15 microL.min(-1)(ultrasonic), and efficiency of
      the devices was 39+/-3% (jet) and 86+/-5% (ultrasonic). Based on these data, a
      total inhalative dose of 2.8 microg iloprost was delivered by jet nebulization
      within 12 min and by ultrasonic nebulization within 4 min, in 18 patients with
      severe primary and secondary pulmonary hypertension (New York Heart Association
      class III and IV), in a randomized crossover design. Haemodynamics were assessed
      by right heart catheterization. Inhalation with the ultrasonic device and jet
      nebulizer, reduced mean+/-SEM pulmonary artery pressure from 54.3+/-2.1 to 47.1+/
      2.0 and from 53.5+/-2.2 to 47.0+/-2.2 mmHg, respectively, and mean+/-SEM
      pulmonary vascular resistance from 1,073+/-109 to 804+/-87 and from 1,069+/-125
      to 810+/-83 dyn.s.cm(-5), respectively. Both modes of aerosolization were well
      tolerated. In conclusion, due to the markedly higher efficiency and output of the
      ultrasonic device, wastage of drug is largely avoided and the duration of
      inhalation can be shortened to one-third, with comparable haemodynamic effects
      and without enforcing side effects.

PMID- 11307744
TI  - Passive respiratory mechanics: the occlusion techniques.
AB  - The aim of this position paper is to define quality control and acceptance
      criteria for measuring passive respiratory mechanics in infants using the
      occlusion techniques to ensure that valid results are obtained. These guidelines
      cover numerous aspects including: 1) terminology and definitions; 2) equipment;
      3) data acquisition; 4) data handling and analysis; 5) reporting of results.
      Adherence to these guidelines should ensure that measurement of passive
      respiratory mechanics in infants in different lung function laboratories could be
      performed with an acceptable degree of safety, precision, and reproducibility.
      This will facilitate multi-centre collection of data and performance of clinical
      investigations.

PMID- 11307745
TI  - Yellow nail syndrome: does protein leakage play a role?
AB  - Yellow nail syndrome is characterized by primary lymphoedema, recurrent pleural
      effusion and yellow discoloration of the nails. Although mechanical lymphatic
      obstruction is assumed to be the underlying pathology, it cannot explain the
      common finding of high albumin concentration in the pleural space. This paper
      describes a case of yellow nail syndrome presenting with the classical triad of
      lymphoedema, recurrent pleural effusion and yellow discoloration of the nails,
      associated with persistent hypoalbuminaemia and increased enteric loss of
      albumin. Based on the findings in this case and those in the literature, it is
      speculated that increased microvascular permeability may contribute to the
      pathogenesis of this syndrome.

PMID- 11307746
TI  - Sleep apnoea and Turner's syndrome.
AB  - A 32-yr-old female with Turner's syndrome and anatomical craniofacial
      abnormalities, presented with obstructive sleep apnoea syndrome. This was
      initially treated by nasal continuous positive airway pressure and secondarily
      cured by maxillomandibullar advancement osteotomy. Anatomical upper airway
      abnormalities and hormonal factors, which predispose Turner patients to develop
      obstructive sleep apnoea syndrome, are discussed. A systematic assessment and
      treatment of sleep-disordered breathing is probably of interest in these
      patients.

PMID- 11307747
TI  - Allergic bronchopulmonary aspergillosis in cystic fibrosis.

PMID- 11307748
TI  - Systemic bioavailability of inhaled steroids: the importance of appropriate and
      comparable methodology.

PMID- 11307749
TI  - Role of NO pathway, calcium and potassium channels in the peripheral pulmonary
      vascular tone in dogs.
AB  - Because hypoxic pulmonary vasoconstriction occurs mainly in the small pulmonary
      arteries, the authors investigated the effects of drugs acting on the nitric
      oxide (NO) pathway and the calcium and potassium channels in the peripheral
      pulmonary circulation, without interference with the overall pulmonary or
      systemic circulation. Mixed venous blood was infused in wedged areas to study the
      pressure/flow relationship and to compute peripheral pulmonary vascular
      resistance (PPVR). The authors studied the effects of Nomega-nitro-L-arginine
      methyl ester (L-NAME), an NO synthase inhibitor, sodium nitroprusside (SNP, an NO
      donor), the calcium channel blockers verapamil, nifedipine and nicardipine, and
      the potassium channel opener levcromakalim, during normoxia and acute mild
      normocapnic hypoxia. In the peripheral pulmonary circulation, L-NAME caused an
      increase in PPVR during normoxia (+95%; p<0.001) and hypoxia (+60%; p<0.01).
      Following the increase by L-NAME, SNP decreased PPVR during normoxia (-24%;
      p<0.05) and hypoxia (-23%; p<0.05). Verapamil, nifedipine and nicardipine did not
      modify PPVR during normoxia but during hypoxia they decreased PPVR (-28%,
      nonsignificant; -27%, p<0.01 and -33%, p<0.05, respectively). Levcromakalim did
      not modify PPVR during normoxia or hypoxia. In conclusion, the nitric oxide
      pathway and voltage-dependent calcium channels, and not adenosine triphosphate
      sensitive potassium channels, play an important role in the control of peripheral
      pulmonary circulation in dogs.

PMID- 11307750
TI  - Inflammation in cystic fibrosis airways: relationship to increased bacterial
      adherence.
AB  - It is unclear whether inflammation in the cystic fibrosis (CF) lung relates
      predominantly to bacterial infection, or occurs as a direct consequence of mutant
      cystic fibrosis transmembrane conductance regulator (CFTR) protein. Interleukin
      (IL)-8 secretion from CF and non-CF cell lines, and from CF and non-CF human
      primary nasal epithelial cells incubated with or without Pseudomonas aeruginosa,
      was measured. Activation of nuclear factor-kappaB (NF-kappaB) in unstimulated CF
      and non-CF nasal epithelial cells, cell lines and murine tissues was measured by
      gel-shift assays. No significant difference in basal IL-8 production or NF-kappaB
      activation was observed between CF and non-CF primary nasal cells. However, CF
      cells exhibited a significantly (p<0.01) increased IL-8 secretion following P.
      aeruginosa stimulation. Equalization of the increased P. aeruginosa adherence
      observed in CF cells, to non-CF levels, resulted in comparable IL-8 secretion.
      Further, IL-8 production did not differ with mutations which result in either
      correctly localized CFTR, or in partial/total mislocalization of this protein.
      Similar levels of NF-kappaB activation were observed in a number of organs of
      wildtype and CF mice. Finally, IL-8 secretion and NF-kappaB activity were not
      consistently increased in CF cell lines. Cos-7 cell transfection with plasmids
      expressing deltaF508 or G551D mutant CFTR protein resulted in increased
      activation of a p50-containing NF-kappaB complex, but IL-8 secretion was similar
      to wild-type cells. The authors conclude that the stimulus produced by
      Pseudomonas aeruginosa is the predominant inflammatory trigger in their models.

PMID- 11307751
TI  - Nebulized heparin in Burkholderia cepacia colonized adult cystic fibrosis
      patients.
AB  - Viscous negatively charged cystic fibrosis (CF) sputum allows colonization by
      pathogens, inducing a chronic inflammatory response. Heparin thins sputum by
      decreasing the mucin molecule amino group negative charge, altering its
      intermolecular hydrogen bonding, and ionically shielding its polyionic moieties.
      It also has an anti-inflammatory effect within the lung. It may, therefore, be
      useful in the treatment of CF patients. In order to test this, six fully informed
      Burkholderia cepacia colonized stable adult CF patients, received 25,000 IU
      nebulized heparin sulphate daily for 7 days. Subjective sputum parameters,
      spirometry, platelets, coagulation parameters, and serum and sputum interleukin
      (IL)-6 and -8 were measured before and after treatment. All patients tolerated
      the heparin with no evidence of bleeding, thrombocytopenia or change in
      coagulation parameters. There was no change in spirometry, but a reduction in
      interleukins (sputum IL-6, p=0.01; sputum IL-8, p=0.002; serum IL-6, p=0.02;
      serum IL-8, p=0.02). Sputum was easier to expectorate (p < 0.04), with a trend
      towards thinner sputum (p=0.07) but no change in sputum volume. Heparin therapy
      was well tolerated and had an anti-inflammatory effect, with subjective sputum
      mucolysis. Further studies are necessary to define the role of heparin in the
      treatment of cystic fibrosis patients.

PMID- 11307752
TI  - Nedocromil sodium versus sodium cromoglycate in treatment of exercise-induced
      bronchoconstriction: a systematic review.
AB  - The objective of this review was to compare the effects of prophylactic doses of
      nedocromil sodium (NCS) and sodium cromoglycate (SCG) on postexercise lung
      function, in persons diagnosed with exercise-induced bronchoconstriction.
      Randomized controlled trials were identified from the Cochrane Airways Review
      Group Asthma Register, plus hand searching for trials in journals, bibliographies
      of relevant studies and review articles. Randomized controlled trials comparing
      NCS to SCG in prophylactic treatment of exercise-induced bronchoconstriction were
      eligible. Studies were pooled using odds ratios (OR) for dichotomous outcomes or
      weighted mean differences (WMD) with 95% confidence intervals (95% CI) for
      continuous outcomes. No significant differences were noted between NCS and SCG
      with respect to the maximum per cent decrease in forced expiratory volume in one
      second (WMD=-0.88; 95% CI -4.50-2.74), complete protection (OR=0.95; 95% CI 0.50
      1.81), clinical protection (OR=0.71; 95% CI 0.36-1.39), unpleasant taste
      (OR=6.85; 95% CI 0.77-60.73), or sore throat (OR=3.46; 95% CI 0.32-37.48).
      Subgroup analyses based on age, dosages of medications and timing of exercise
      postinhalation were consistent with the overall pooled analyses. No significant
      differences were evident between the effects of nedocromil sodium and sodium
      cromoglycate during the immediate postexercise period in adults and children with
      exercise-induced bronchoconstriction, with regards to maximum per cent decrease
      in forced expiratory volume in one second, complete protection, or clinical
      protection. Side-effect profiles were similar.

PMID- 11307753
TI  - Inflammation and infection in cystic fibrosis--hen or egg?

PMID- 11307754
TI  - Methacholine inhalation challenge: a shorter, cheaper and safe approach.
AB  - Increased nonspecific bronchial hyperresponsiveness to pharmacological agents
      such as histamine or methacholine (MCh) is a hallmark of asthma. The measurement
      of airway reactivity is quite sensitive but testing is tedious, and time and
      money consuming. The present aim was, therefore, to design the shortest possible,
      yet safe inhalation challenge protocol applicable for a lung function referral
      centre. All records of studies performed in our institution during 1996 were
      analyzed retrospectively with a baseline ratio (bl) of forced expiratory volume
      in one second/forced vital capacity (FEV1/FVC) > or = 0.7 (n=449). It was
      questioned what the initial dose should be, and whether some inhalation steps
      could have been skipped without losing pertinent information and/or causing an
      adverse response (a fall in FEV1 >40%). When unavailable, provocative dose
      causing a 20% fall in FEV1 (PD20) values were obtained by linear inter- or
      extrapolation of the existing data. The present study showed that three-fold
      concentration steps could have been employed with minimal change in outcome. Only
      151449 patients (3.3%) would have experienced a severe response. Five subjects
      (of 169, 3.0%) with FEV1/FVCbl 0.7-0.8 reacted to inhalation up to 0.073
      micromol. Four subjects (of 280, 1.4%) with FEV1/ FVCbl> or =0.8 reacted to
      inhalation up to 0.219 micromol. The authors suggest that: 1) an initial dose of
      0.219 micromol (initial concentration= 0.21 mg.mL(-1)) may be used when the
      baseline ratio of forced expiratory volume in one second to forced vital capacity
      > or =0.8 and 0.073 micromol (initial concentration=0.07 mg.mL(-1)) when the
      baseline ratio is <0.8; 2) a tripling dose protocol is easier to perform, cheaper
      and 30.2%, faster, yet just as safe; and 3) other abbreviated protocols used in
      epidemiologic settings may not be applicable in a referral centre setting.

PMID- 11307755
TI  - Development and validation of the Adolescent Asthma Quality of Life Questionnaire
      (AAQOL).
AB  - Current asthma-specific quality of life questionnaires have major conceptual and
      methodological deficiencies for use in adolescents. The aim of this study was to
      develop and validate the "Adolescent Asthma Quality of Life Questionnaire
      (AAQOL)", specifically developed for adolescents with asthma. One-hundred and
      eleven adolescents with frequent-episodic or persistent asthma aged 12-17 yrs
      were recruited from three tertiary paediatric asthma clinics. The standardized
      multi-step method consisted of: 1) item selection including semistructured
      interviews (n=14); 2) item reduction and validation (n=66); and 3) assessment of
      reproducibility (n=31). Item reduction was performed applying the clinical impact
      method. The 32 item AAQOL covers six domains: symptoms, medication, physical
      activities, emotion, social interaction and positive effects. There was high
      internal consistency for the six domains (alpha=0.70-0.90) and for the total
      score (alpha=0.93). Test-retest reliability was high for all domain scores
      (r=0.76-0.85) and the total score (r=0.90), indicating high reproducibility of
      the AAQOL. There was high correlation with the paediatric Asthma Quality of Life
      Questionnaire (rho=0.81) which focuses primarily on symptoms and emotional well
      being. There was weak to moderate correlation with clinical parameters of asthma
      severity (rho=0.25-0.65). The 32-item Adolescent Asthma Quality of Life
      Questionnaire is a valid, developmentally age-appropriate and dimensionally
      comprehensive asthma-specific quality of life measure for use in adolescents.

PMID- 11307756
TI  - Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British
      asthmatics.
AB  - Whole genome scan analyses have revealed that chromosomal region 3p21-24, which
      contains a gene cluster of CC chemokine receptors such as CCR3, is possibly
      linked to asthma. Because CCR3 ligands play a pivotal role in the selective
      recruitment and activation of inflammatory cells in the asthmatic airway, the
      authors examined whether there is any association between asthma and the CCR3
      gene polymorphisms. Three polymorphisms were identified using the single stranded
      conformational polymorphism method in Japanese (Asian) and British (Caucasian)
      subjects; one silent mutation T51C and two missense mutations G824A and T971C.
      These polymorphisms were examined in 391 Japanese subjects (210 asthmatics and
      181 nonasthmatic controls) and 234 British subjects (142 asthmatics and 92
      nonasthmatic controls). Asthma diagnosis was based on episodic symptoms,
      documented wheeze, and the presence of reversible airflow limitation. CCR3 T51C
      demonstrated a significant association with the diagnosis of asthma in the
      British population (odds ratio 2.35, p<0.01), but not in the Japanese population.
      Multiple logistic regression analysis also showed that CCR3 T51C was associated
      with asthma (odds ratio 2.83, p < 0.02), independent of atopic phenotypes such as
      high levels of total or house dust mite-specific immunoglobulin-E in serum. In
      conclusion, a significant association between asthma and CCR3 T51C polymorphism
      localized on chromosome 3p21 was found.

PMID- 11307757
TI  - Trials of inhaled iloprost and other new vasodilating prostaglandins.

PMID- 11307758
TI  - Bronchoconstriction induced by inhaled adenosine 5'-monophosphate in subjects
      with allergic rhinitis.
AB  - Adenosine and its related nucleotide, adenosine 5'-monophosphate (AMP) induce
      bronchoconstriction in asthmatics, probably caused by histamine release from
      airway mast cells. The objective of this study was to determine the effect of
      inhaled AMP on lung function in subjects with allergic rhinitis. A total of 52
      adults (28 subjects with allergic rhinitis, 14 asthmatics and 10 healthy
      subjects) were challenged with increasing concentrations of AMP and methacholine.
      Airflow was assessed after each concentration and the response to each
      bronchoconstrictor agent was measured by the provocative concentration required
      to produce a 20% fall (PC20) in forced expired volume in one second (FEV1). All
      14 asthmatics, 10 subjects with allergic rhinitis and none of the healthy
      controls were hyperresponsive to AMP. Subjects with allergic rhinitis had higher
      prevalence of hyperresponsiveness to AMP than healthy controls (p=0.038).
      Although the prevalence of hyperresponsiveness for methacholine and for AMP in
      subjects with allergic rhinitis was similar (39% and 36%, respectively), four
      subjects had hyperresponsiveness to methacholine but not to AMP, whereas three
      subjects had hyperresponsiveness to AMP but not to methacholine. To conclude,
      inhaled adenosine 5'-monophosphate causes airway narrowing in a significantly
      higher proportion of subjects with allergic rhinitis than healthy volunteers.
      Furthermore, methacholine and adenosine 5'-monophosphate hyperresponsiveness are
      not detected in the same individuals with allergic rhinitis, thus suggesting that
      responsiveness to the two bronchoconstrictor stimuli is not reflecting the same
      abnormalities of the airways.

PMID- 11307759
TI  - Respiratory impedance response to continuous negative airway pressure in awake
      controls and OSAS.
AB  - The aim of the study was to determine whether the response of respiratory
      impedance (Zrs) to decreasing levels of continuous negative airway pressure
      (CNAP) during wakefulness, differs in controls and subjects with obstructive
      sleep apnoea syndrome (OSAS). Zrs was measured by the forced oscillation
      technique (4-32 Hz) in 15 controls and 21 patients with OSAS (apnoea/hypopnoea
      index >20 per sleep hour) with normal lung function, in the basal state and with
      application of decreasing CNAP of -5, -10, and -15 hPa. Respiratory resistance
      was extrapolated to 0 Hz (R0) and estimated at 16 Hz (R16) by linear regression
      analysis of respiratory resistive impedance versus frequency. Respiratory
      elastance (Ers) and inertance (Irs) were estimated by multilinear regression
      analysis of respiratory reactance versus frequency, and resonance frequency (RF)
      was determined as RF=(1/2pi)(Ers/Irs)0.5. In both groups, R0, R16, Ers and RF
      significantly increased as the CNAP level decreased (p <0.0001 for all). R0, Ers,
      and RF increased significantly more in OSAS than in controls (p < 0.01, 0.001,
      and 0.0001, respectively), independently of the severity of obesity. Receiver
      operator characteristic curves showed that the parameter which best detected OSAS
      was RF, with a sensitivity of 81% and 93% specificity for the 13.6 Hz cut-off
      point. The results of the present study suggest that the response of respiratory
      impedance to decreasing continuous negative airway pressure levels, might allow
      detection of obstructive sleep apnoea syndrome in subjects with normal lung
      function.

PMID- 11307760
TI  - Magnetic resonance imaging of the pharynx in OSA patients and healthy subjects.
AB  - Obstructive sleep apnoea (OSA) occurs because of recurrent narrowing and
      occlusion of the velopharynx (VP) during sleep. The specific cause of OSA is
      unknown. Cephalometric radiography, fibreoptic nasopharyngoscopy, acoustic
      reflection techniques, and computerized tomography have limitations (dynamic and
      tridimensional evaluation) in the mechanism of occlusion investigation. Static
      and dynamic examination of the soft tissue structures surrounding the upper
      airway during the respiratory cycle in wakefulness and sleep, can lead to a
      better understanding of the process. Ultrafast magnetic resonance imaging (one
      image per 0.8 s) was used to study the upper airway and surrounding soft tissue
      in 17 patients with OSA during wakefulness and sleep, and in eight healthy
      subjects whilst awake. The major findings of this investigation in the 25
      subjects were as follows: 1) the VP was smaller in apnoeic patients, only during
      part of the respiratory cycle; 2) the variation in VP area during the respiratory
      cycle was greater in apnoeic patients than in controls, particularly during
      sleep, suggesting an increased compliance of the VP in these patients; 3) VP
      narrowing was similar in the lateral and anterior-posterior dimensions, both in
      controls and apnoeic patients while awake; apnoeic patients during sleep have a
      more circular VP upon reaching the minimum area; 4) there was an inverse
      relationship between dimensions of the lateral pharyngeal walls and airway area,
      probably indicating that lateral walls are passively compressed or stretched as a
      result of changes in the airway calibre; and 5) soft palate and parapharyngeal
      fatpads were larger in apnoeic patients, although their role in the genesis of
      OSA is uncertain. It was concluded that changes in the velopharynx area and
      diameter during the respiratory cycle are greater in apnoeic patients than in
      normal subjects, particularly during sleep. This suggests that apnoeic patients
      have a more collapsible velopharynx, this being the main mechanism of
      obstruction.

PMID- 11307761
TI  - Long-term treatment of pulmonary hypertension with aerosolized iloprost.
AB  - Pulmonary arterial hypertension (PAH), defined as elevated pulmonary arterial
      pressure and pulmonary vascular resistance, is an end-point of a variety of
      conditions. The only therapy that has been shown to improve both quality of life
      and survival is intravenous prostacyclin (prostaglandin I2 (PGI2), epoprostenol).
      The effect of long-term aerosolized iloprost (Ilomedin, Schering, Berlin, Germany
      and Vienna, Austria), a stable prostacyclin analogue and potent vasodilator, on
      haemodynamics and functional status was investigated in 12 patients with severe
      pulmonary hypertension. Haemodynamic measurements and vasodilator testing by
      right heart catheterization were performed prior to and after long-term iloprost
      inhalation therapy. Haemodynamic improvement or increased exercise tolerance was
      not observed in any of the patients. After a mean+/-SD treatment period of 10+/-5
      months, mean+/-SD pulmonary vascular resistance had increased from 11+/-3 Wood
      Units (mmHg.L(-1).min) to 13+/-4 Wood Units, with unchanged arterial oxygen
      saturation (92+/-4%, versus 91+/-4%). Within the study period, three patients
      went into right heart failure and had to be placed on intravenous epoprostenol.
      The authors conclude that inhaled iloprost in addition to conventional therapy in
      the presently recommended dose of 100 microg.day(-1) delivered in 8-10 2 h
      portions, is not an efficient vasodilator therapy in severe pulmonary
      hypertension. It remains to be shown whether dose increases and/or combination
      protocols will be effective, or whether inhalation of iloprost may be safe for
      selected cases of pulmonary hypertension.

PMID- 11307762
TI  - Reappraisal of the aetiology and prognostic factors of severe acute respiratory
      failure in HIV patients.
AB  - The introduction of highly active antiretroviral therapy with protease inhibitors
      in 1996 has changed the morbidity and mortality of acquired immune deficiency
      syndrome patients. Therefore, the aetiologies and prognostic factors of human
      immunodeficiency virus (HIV)-infected patients with life-threatening respiratory
      failure requiring intensive care unit (ICU) admission need to be reassessed. From
      1993 to 1998, we prospectively evaluated 57 HIV patients (mean+/-SEM age 36.5+/
      1.3 yrs) admitted to the ICU showing pulmonary infiltrates and acute respiratory
      failure. A total of 21 and 30 patients were diagnosed as having Pneumocystis
      carinii and bacterial pneumonia, respectively, of whom 13 and eight died during
      their ICU stay (p=0.01). Both groups of patients had similar age, Acute
      Physiology and Chronic Health Evaluation (APACHE) II score, and severity in
      respiratory failure. The number of cases with bacterial pneumonia admitted to ICU
      decreased after 1996 (p=0.05). Logistic regression analysis showed that (APACHE)
      II score >17, serum albumin level <25 g.(-1), and diagnosis of P. carinii
      pneumonia were the only factors at entry associated with ICU mortality (p=0.02).
      Patients with bacterial pneumonia are less frequently admitted to the intensive
      care unit after the introduction of highly active antiretroviral therapy with
      protease inhibitors in 1996. Compared to the previous series, it was observed
      that the few Pneumocystis carinii pneumonia patients that need intensive care
      still have a bad prognosis.

PMID- 11307763
TI  - Plethysmography for the assessment of pneumococcal pneumonia and passive
      immunotherapy in a mouse model.
AB  - The increasing prevalence of resistance to antibiotics of Streptococcus
      pneumoniae, the main causative agent of community-acquired bacterial pneumonia,
      necessitates the development of both new therapeutic strategies and noninvasive
      methods in order to evaluate their efficacy. The efficacy of passive
      immunotherapy with human intravenous immunoglobulin (IVIG) or solvent alone,
      administered intranasally or intravenously, was evaluated in a mouse model of
      acute pneumonia. Lung bacterial load was also evaluated, using a classical but
      invasive method, as was respiratory function (minute ventilation, respiratory
      frequency and tidal volume) using plethysmography, a simple noninvasive method
      commonly used in inhalation toxicology, but not previously used to assess
      respiratory infection. Forty-eight hours after infectious challenge, the lung
      bacterial load was significantly lower in IVIG-treated mice than in untreated
      mice. At the same time, minute ventilation was significantly lower than reference
      values for untreated mice (36+/-3 versus 57+/-8 mL.min(-1), p<0.01, and 31+/-2
      versus 50+/-5 mL.min(-1), p<0.01 for intranasal and intravenous administration of
      solvent, respectively) but not in mice treated with IVIG by either route of
      administration. Plethysmography therefore appears to be a simple and reliable
      test for the follow-up of acute respiratory infection.

PMID- 11307764
TI  - British Society for Investigative Dermatology, annual meeting. Warwick, 9-11
      April 2001. Abstracts.

PMID- 11307765
TI  - 47th Annual Conference of the American Society for Artificial Internal Organs.
      New York, New York, USA. June 7-9, 2001. Abstracts.

PMID- 11307766
TI  - American Society of Regional Anesthesia and Pain Medicine Annual Meeting. May 10
      13, 2001. Vancouver, British Columbia, Canada. Abstracts.

PMID- 11307767
TI  - [Neoadjuvant strategies in the treatment of non-small cell lung cancer].
AB  - The prognosis of patients with resectable non-small cell lung cancer (NSCLC),
      other than stage IA disease, remains disappointing, with 5 year survival rates
      ranging from 40-55%. For the past 15-20 years, several phase II trials have
      investigated the efficacy of chemotherapy and chemoradiotherapy prior to surgery
      in the management of stage IIIA NSCLC, with encouraging results. Phase III trials
      comparing surgery alone with chemotherapy plus surgery have confirmed the
      efficacy of this multimodality approach. Gemcitabine, one of the new agents with
      significant activity against NSCLC, has undergone extensive clinical testing in
      combination with cisplatin in this setting. In 47 patients with stage IIIA
      disease, induction with gemcitabine/cisplatin was well tolerated and yielded a
      response rate of >70%. Downstaging of the mediastinal lymph nodes occurred in 53%
      of patients. Preliminary data from another study employing mitomycin C,
      ifosfamide and cisplatin in resectable NSCLC suggest that there are favourable
      effects of induction treatment, especially in early-stage disease. With the
      availability of chemotherapeutic combinations such as gemcitabine/cisplatin,
      which are both effective and well tolerated, combination therapy is likely to
      become a major advance in the treatment of patients with early-stage (IB, II)
      NSCLC.

PMID- 11307768
TI  - [Gemcitabine + Cisplatin combinations in advanced non-small cell lung cancer].
AB  - Until recently there was widespread scepticism among oncologists about the true
      benefit of chemotherapy in patients with non-small cell lung cancer. The results
      of randomised trials comparing the efficacy of chemotherapy in addition to the
      best palliative treatments with the same supportive care given alone have been
      contradictory. It has been necessary to wait for the publication of a number of
      meta-analyses during the 1990s to have scientific evidence of the efficacy of
      cytotoxic therapy on the mean survival time of patients with metastatic tumours.

PMID- 11307769
TI  - [Chemotherapy of non-small cell lung cancer: non-cisplatin based combinations].
AB  - The rationale for the association of two cytotoxic agents is based on obtaining
      the best possible synergy with the lowest level of interactive toxicity. The
      original mechanism of action of gemcitabine makes this drug a logical choice in
      the treatment of non-small cell lung cancer (NSSLC). Numerous phase I and phase
      II studies assessing the use of gemcitabine-based combinations in NSSLC are
      currently underway. These associations without cisplatin will quite naturally be
      positioned as second line therapy for NSSLC. The high response rates, however,
      also make these combinations particularly interesting candidates for first-line
      therapy, and they are shortly to be compared in phase II trials with traditional
      cisplatin-based treatment regimens. Protocols using cisplatin-based associations
      already have proven efficacy, but the same is expected to apply to other
      protocols without cisplatin, particularly those using innovative drugs such as
      gemcitabine, vinorelbine and taxanes. The different studies already concluded, or
      those currently underway, therefore constitute a basis for developing sequential
      treatment strategies in NSSLC. Gemcitabine is one of the new tools available to
      practitioners to improve patient prognosis in terms of clinical benefits and
      improved survival.

PMID- 11307770
TI  - [Current treatment of bladder cancer: from epidemiology to surgical treatment].
AB  - Urothelial carcinoma of the bladder accounts for over 95% of bladder tumours in
      France. The incidence of this disease is increasing in industrialised countries.
      Several types of bladder cancer can be distinguished: (1) superficial tumours
      which have a risk of recurrence and progression, although conservative treatment
      based on endoscopic resection possibly followed by adjuvant therapy is a feasible
      option; (2) muscle-invasive tumours which require radical treatment; and (3) a
      group of so-called superficial tumours which require particularly close
      monitoring since they present a high risk of progression. Management of bladder
      tumours requires assessment of their potential to progress to a more invasive
      stage, and also consideration of a number of prognostic factors including
      endoscopic, histological and biological findings.

PMID- 11307772
TI  - Disappearance of chromosomal abnormalities and recovery of hematopoiesis after
      immunosuppressive therapy for hypoplastic refractory anemia with excess of
      blasts.

PMID- 11307771
TI  - [Gemcitabine and urothelial tumours].
AB  - Since 1985, standard chemotherapy of metastatic urothelial tumours has been based
      on a combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC
      protocol). Two major lessons have been learned from the use of M-VAC, namely,
      clear evidence of chemo-sensitivity, and an absence of chemo-curability
      associated with notable toxicity. Three phase II studies using gemcitabine
      monotherapy have demonstrated promising efficacy with an objective response rate
      of 22-28%, and a satisfactory toxicity profile. Three further phase II studies
      have confirmed the efficacy of gemcitabine in association with cisplatine (GC
      protocol), with a response rate of 42-66%, of which 18-28% were complete
      responses. The main adverse effects were haematological, including neutropenia,
      or grade 3 or 4 thrombocytopenia without any symptoms of fever or significant
      haemorrhage. Current research with gemcitabine in the treatment of urothelial
      tumours is aimed at optimising administration of the GC protocol, investigating
      the use of gemcitabine in association with other cytotoxic agents such as
      taxanes, or expanding the use of this drug as adjuvant therapy. The results of a
      phase III study to compare the efficacy and toxicity of the M-VAC and GC
      protocols are eagerly awaited.

PMID- 11307773
TI  - Discrepancy between phenotype and genotype on screening for factor V Leiden after
      transplantation.

PMID- 11307774
TI  - Serum viral interleukin-6 in AIDS-related multicentric Castleman disease.

PMID- 11307775
TI  - Development of a myeloproliferative disorder in a patient with monoclonal
      gammopathy of undetermined significance secreting immunoglobulin of the M class
      and treated with thalidomide and anti-CD20 monoclonal antibody.

PMID- 11307776
TI  - Expression of CD10 by human T cells that undergo apoptosis both in vitro and in
      vivo.

PMID- 11307777
TI  - Angiogenesis is increased in B-cell chronic lymphocytic leukemia.

PMID- 11307778
TI  - Cationic peptides from leukocytes might kill bacteria by activating their
      autolytic enzymes causing bacteriolysis: why are publications proposing this
      concept never acknowledged?

PMID- 11307779
TI  - [Treatment with statins for the reduction of cardiovascular risk].

PMID- 11307780
TI  - [The promise of statins].
AB  - Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors,
      are a class of drugs with a potent lipid-lowering effect that have been shown to
      reduce LDL cholesterol by 35-45% at therapeutic doses. Recent trials have
      demonstrated that in subjects with coronary artery disease, an aggressive
      treatment with high doses of statins, which lowers LDL cholesterol below 100
      mg/dl, can obtain better results in terms of reduction of cardiovascular events,
      compared to the currently used dosage of statins. The pharmacologic effect of
      statins is far beyond the mere reduction of LDL cholesterol, in that it has been
      demonstrated that they are able to inhibit the proliferation of smooth muscle
      cells and macrophages, to restore the endothelial activity, and to inhibit the
      inflammatory response of macrophages. These effects have been called "pleiotropic
      effects" of statins. These metabolic activities of statins play an important role
      in contrasting the inflammatory elements of the atherosclerotic plaque. The
      atherosclerotic plaque is formed by a lipid core and a fibrous cap. Smooth muscle
      cells, macrophages and T lymphocytes are present in the plaque, particularly in
      the fibrous cap. In stable plaques, smooth muscle cells produce extracellular
      matrix, i.e. collagen and elastin, which strengthens the fibrous cap. In the
      presence of inflammatory stimuli, primarily oxidized LDL, T lymphocytes activate
      macrophage and smooth muscle cells to secrete cytokines and proteolytic enzymes,
      the collagenolytic metalloproteases, that can weaken the extracellular matrix and
      rupture the fibrous cap. A local thrombotic mechanism starts in the ruptured
      plaque, promoted by the tissue factor released by macrophages in the lipid core
      of the plaque, which can propagate to the coronary lumen with total occlusion.
      Statins have been demonstrated to contrast the inflammatory activity of
      macrophages and smooth muscle cells, inducing smooth muscle cells to secrete
      extracellular matrix which strengthens the fibrous cap and prevents rupture. At
      present, the primary target of statins is LDL cholesterol reduction, but with
      additional effects on the inflammatory cell of the plaque with a reduction in
      macrophages and secretion of collagenolytic metalloproteases and reinforcing the
      fibrous skeleton of the plaque by increasing the content of interstitial
      collagen.

PMID- 11307781
TI  - [Characteristics of a statine of the most recent generation].
AB  - LDL cholesterol levels are directly related to increased risk of cardiovascular
      disease. Several classes of drugs are available for the reduction of high
      cholesterol levels, but the highest efficacy has been demonstrated by HMG-CoA
      reductase inhibitors (statins). Cerivastatin is a third generation, synthetic
      statin, characterized by the highest pharmacological and therapeutic potency
      among currently marketed statins, and whose lipid-lowering efficacy has been
      demonstrated in a number of large, multicenter trials. Along with improvements in
      triglycerides and HDL cholesterol, cerivastatin at the dosage of 0.4 mg/day
      achieved a mean 36% reduction in LDL cholesterol. Analysis of clinical trials
      indicates that the molecule has age and gender-related effects, with a greater
      cholesterol reduction in women than in men and in elderly than younger patients.
      Cerivastatin has a dual hepatic metabolism pathway, via the CYP3A4 and CYP2C8
      isoenzymes of cytochrome P450; therefore no potentially significant drug
      interactions with other CYP3A4 inhibitors, for instance erythromycin and
      itraconazole, have been reported. Cerivastatin tolerability profile at dosages
      investigated is similar to that of placebo.

PMID- 11307782
TI  - [Heart arrest].
AB  - Cardiac arrest is one of the leading causes of mortality in industrialized
      countries and is mainly due to ischemic heart disease. According to ISTAT
      estimates, approximately 45,000 sudden deaths occur annually in Italy whereas
      according to the World Health Organization, its incidence is 1 per 1000 persons.
      The most common cause of cardiac arrest is ventricular fibrillation due to an
      acute ischemic episode. During acute ischemia the onset of a ventricular
      tachyarrhythmia is sudden, unpredictable and often irreversible and lethal. Each
      minute that passes, the probability that the patient survives decreases by 10%.
      For this reason, the first 10 min are considered to be priceless for an
      efficacious first aid. The possibility of survival depends on the presence of
      witnesses, on the heart rhythm and on the resolution of the arrhythmia. In the
      majority of cases, the latter is possible by means of electrical defibrillation
      followed by the reestablishment of systolic function. An increase in equipment
      alone does not suffice for efficacious handling of cardiac arrest occurring
      outside the hospital premises. Above all, an adequate intervention strategy is
      required. Ambulance personnel must be well trained and capable of intervening
      rapidly, possibly within the first 5 min. The key to success lies in the
      diffusion and proper use of defibrillators. The availability of new generation
      instruments, the external automatic defibrillators, encourages their widespread
      use. On the territory, these emergencies are the responsibility of the 118
      organization based, according to the characteristics specific to each country, on
      the regulated coordination between the operative command, the crews and the first
      aid means. Strategies for the handling of these emergencies within hospitals have
      been proposed by the Conference of Bethesda and tend to guarantee an efficacious
      resuscitation with a maximum latency of 2 min between cardiac arrest and the
      first electric shock. The diffusion of external automatic defibrillators is a
      preventive measure. Such equipment has permitted early defibrillation by non
      medical first-aid personnel. These instruments contain software capable of
      recognizing an arrhythmia which may be defibrillated and of instructing the
      operator whether and when to press the defibrillation button. The latest
      instruments deliver the shock by means of a biphasic wave necessitating a lesser
      amount of energy which can be provided by lighter condensers. Thus such equipment
      weighs just a couple of kilograms. As suggested by ILCOR, for reasons of
      priority, such instruments should not only be available within hospitals and in
      ambulances but also on the territory, in particular in more crowded places. The
      availability of external automatic defibrillators in such places should reduce
      the time latency before intervention and thus increase survival. The ILCOR
      guidelines have suggested the constitution of an itinerary team well equipped for
      defibrillation and composed of trained personnel of State Institutions such as
      the Municipal Police, Traffic Police and the Fire Brigades. With regard to the
      majority of arrhythmias amenable to defibrillation which occur at home or in less
      crowded places, other strategies, such as primary prevention and training
      programs for categories at increased risk, must be employed. Antiarrhythmic drugs
      have long been considered the best solution for the prevention and treatment of
      ventricular tachyarrhythmias. However, the approach to these pathologies has
      drastically changed during the last few years owing to accumulating evidence in
      favor of defibrillators which may be implanted for the primary and secondary
      prevention of malignant ventricular arrhythmias. For patients with previous
      cardiac arrest, randomized studies have proven the advantages of such an approach
      compared to medical therapy. On the basis of the above, the guidelines for the
      use of antiarrhythmic implants have been modified. In most western countries, the
      laws regarding this aspect of medicine have recently been renewed. In the United
      States, where there is the "Law of the Good Samaritan", in order to protect and
      acquit persons who give first-aid, many states have adopted new laws which
      promote the use of external automatic defibrillators. Following recent
      dispositions by the President of the United States that defibrillators should be
      present in all Federal properties and on civil aircraft, a new Federal Law is
      about to pass. Italy lacks legislation regarding the use of defibrillators: in
      order to rectify this position, which is still anchored to existing dispositions
      of the civil and penal codes including those regarding the omission of first-aid,
      a bill entitled "The definition and modalities of the use of the external cardiac
      defibrillator" has recently been presented.

PMID- 11307783
TI  - [Long QT syndrome and Brugada syndrome: 2 aspects of the same disease?].
AB  - In clinical cardiology, resort has recently been made to molecular genetics in
      order to explain some mechanisms that underlie sudden cardiac death in young
      people with structurally normal hearts. It has become evident that genetic
      mutations regarding cardiac ion channels may disrupt the delicate balance of
      currents in the action potential, thus inducing malignant ventricular
      tachyarrhythmias. The cardiac sodium channel gene, SCN5A, is involved in two of
      such arrhythmogenic diseases, the Brugada syndrome and one form of the long QT
      syndrome (LQT3). It is believed that these syndromes result from opposite
      molecular effects: Brugada syndrome mutations cause a reduced sodium current,
      while LQT3 mutations are associated with a gain of function. The effects of class
      I antiarrhythmic drugs have been used to differentiate these diseases.
      Intravenous flecainide is used as a highly specific test to unmask the
      electrocardiographic phenotype of the Brugada syndrome. On the other hand, on the
      basis of experimental and clinical studies, the possibility that the same drugs
      act as a gene-specific therapy in this disorder by contrasting the effect of
      mutations in LQT3 has been explored. Recent evidence shows that phenotypic
      overlap may exist between the Brugada syndrome and LQT3. One large family with a
      SCN5A mutation and a "mixed" electrocardiographic pattern (prolonged QT interval
      and ST-segment elevation) has been reported. Moreover, our recent data showed
      that flecainide challenge may elicit ST-segment elevation in some LQT3 patients.
      The presence of "intermediate" phenotypes highlights a remarkable heterogeneity
      suggesting that clinical features may depend upon the single mutation. Only
      deepened understanding of the genotype-phenotype correlation will allow the
      definition of the individual patient's risk and the development of guidelines for
      clinical management.

PMID- 11307784
TI  - [Reporting echocardiography exams with the G8-Cardio ANMCO software].
AB  - BACKGROUND: The availability of a common computerized program for
      echocardiographic study archiving and reporting at national and/or international
      level could make it possible to standardize the echo reports of different
      echocardiographic laboratories, and to use the wealth of data thus obtainable
      with echocardiography, and to exploit its capillary territorial distribution,
      with the aim of collecting echocardiographic data in a standard format for
      epidemiological, scientific and administrative purposes. METHODS: To develop such
      a software, an ad hoc joint National Association of Hospital Cardiologists and
      Italian Society of Echocardiography task force worked in conjunction with the
      Italian Branch of Agilent Technologies to standardize the phraseology of accepted
      echocardiographic terms and of the quantitative parameters derived from
      transthoracic and transesophageal echocardiographic examination at rest as well
      as during exercise and pharmacological stress, and to develop an ad hoc software.
      This echocardiographic study archiving and reporting program is part of the whole
      G8-Cardio ANMCO software developed to computerize the whole cardiological chart.
      The software has been developed by Agilent Technologies to provide a fast, easy
      access and easy to use report generator for the non-computer specialist using
      DBMS Oracle 7.3 database and Power Builder 5.0 to develop a user-friendly
      interface. RESULTS: The number of qualitative and quantitative variables
      contained in the program is 733 for echocardiography at rest, while it depends on
      the stressor and on the length of the examination for the stress echo
      (dipyridamole 214-384, dobutamine 236-406, exercise 198-392). The program was
      tested and refined in our laboratory between November 1999 and May 2000. During
      this time period, 291 resting and 56 stress echocardiographic studies were
      reported and recorded in a database. On average, each resting echocardiographic
      study lasting 10 +/- 4 (range 5-17) min was recorded using 50 +/- 11 (range 33
      67) variables and 41,566 bytes of hard-disk memory space. Stress
      echocardiographic studies, each lasting 7 +/- 5 (range 5-21) min, were recorded
      using 143 +/- 74 (range 38-194) variables and 38,531 bytes of hard-disk memory
      space. CONCLUSIONS: To our knowledge this software represents the first
      experience of a common computerized program for echo archiving and reporting
      carried out at national level.

PMID- 11307785
TI  - [Electronic medical records: medical and legal aspects, privacy, safety, and
      legal validity].
AB  - Medical records must collect all data concerning in-hospital management of
      patients: data have to be verified and easily retrievable. Clinicians are
      responsible for both format and content of medical records. Respect of patient's
      privacy must be made sure both during on-line management and long-term storage of
      records. Computerization can offer many advantages to clinicians, but needs some
      significant adjustments: training and motivation of operators, arrangement of
      clinical processes and of administrative rules to technological developments.
      Nevertheless, some important results can be afforded: standardization of
      procedures, distribution of univocal, verified and ubiquitous data to all
      concerned operators, protection against undesired retrieval, reliability of
      effective reports. Preliminary condition is a clinical local area network,
      widespread into the institution. Database implementation must follow well
      accepted methodology: flow chart design of data dictionary, standardization of
      data coding, input of verified data, effective reporting. Access to data must be
      controlled by sophisticated and sure password system. Back-up of data must be
      automatically available with adequate timing and methodology. Respect of rules on
      patient's privacy must be realized whenever possible. Complex clinical records
      should be made available, containing data, signals and images (both single frames
      and dynamic sequences), due to continuous technical progress of diagnostic tools.
      Medical records must be available for long periods of time: database engine and
      managing tools must be selected among well accepted and largely available
      producers; informatic assistance must be assured for management and evolution of
      systems over the years.

PMID- 11307786
TI  - [Prevalence of vascular disease in candidates for myocardial revascularization
      with aortocoronary bypass: review of the literature and practical implications].
AB  - BACKGROUND: Cardiovascular disease remains the main cause of death and morbidity
      in the industrialized world. Atherosclerosis is a slowly progressive disease;
      coronary artery disease may be the first presentation of a systemic pathology.
      The association between coronary artery disease and peripheral vascular disease
      has often been confirmed by multicenter trials; nevertheless it still remains a
      subject of debate. METHODS: In order to assess the incidence of coronary artery
      disease and the degree of associated vascular lesions, between January 1997 and
      September 1999, in the Department of Cardiothoracic Surgery of the Second
      University of Naples (Italy), all candidates to coronary artery bypass grafting
      (CABG) were submitted to routine preoperative echo color Doppler study of the
      carotid vessels, abdominal aorta and iliac-femoral arteries. The correlation
      between the echo color Doppler findings, the angiographic patterns of coronary
      lesions and atherosclerotic risk factors was analyzed in all cases. RESULTS:
      Among 540 patients undergoing CABG, 418 (77.4%) had carotid disease, with a
      stenosis > 70% in 62 (11.3%). Forty-nine (79%) patients had asymptomatic severe
      carotid disease. A significant correlation between the severity of coronary
      disease and the incidence of severe carotid disease was found (p = 0.02). An
      abdominal aortic dilation was found in 37 cases (6.7%). Its diameter exceeded 35
      mm in 14 patients (2.5%) and in 8 it was associated with triple vessel coronary
      disease. Atherosclerotic lesions of the iliac-femoro-popliteal axis were found in
      394 (72.9%) patients and strongly correlated with the severity of coronary artery
      disease (p = 0.02); lesions were hemodynamically significant in 91 (16.8%) cases.
      CONCLUSIONS: Our study emphasizes the association between coronary artery disease
      and vascular disease. Non-invasive complete arterial investigation should be
      routinely performed in patients undergoing CABG.

PMID- 11307787
TI  - [Socioeconomic aspects and cardiovascular risk factors: experience at the
      Cardiovascular Epidemiologic Observatory].
AB  - BACKGROUND: Cardiovascular diseases are more frequent among the poorer social
      classes of the population. Studies including social and economic factors offer
      useful information when planning the strategy required in primary prevention. The
      aim of this investigation was to evaluate the association between socio-economic
      levels and cardiovascular risk factors in 3198 women and 3218 men aged 35-74
      years enrolled for a cross sectional study within the Cardiovascular
      Epidemiologic Observatory, carried out in 1998 to evaluate the distribution of
      risk factors and the prevalence of cardiovascular risk conditions. METHODS: The
      level of education was used to determine the socio-economic status; the
      distribution of the risk factors and the prevalence of risk conditions were
      analyzed for the different levels of education. Models of logistic regression
      were used to evaluate the relation between the socio-economic status and obesity,
      cigarette smoking, hypertension, and hypercholesterolemia. RESULTS: A higher
      level of education is significantly protective against both obesity and cigarette
      smoking. With regard to obesity among males compared to those with a university
      degree the odds ratio increased to 1.6 for those with an upper secondary
      education diploma (95% confidence interval--CI 1.09-2.51) and to 3.5 for those
      without any qualification (95% CI 1.97-6.21). Among women the odds ratio
      increased to 3.2 (95% CI 1.81-5.81) and to 4.8 (95% CI 2.55-8.98) for the same
      levels of education. With regard to smoking among males compared to those with a
      university degree the odds ratio increased to 1.4 for those holding an upper
      secondary education diploma (95% CI 1.07-1.94) and to 2.3 for those without any
      qualification (95% CI 1.40-3.68). For men living in central or southern Italy,
      the odds ratio for cigarette smoking increased to 1.3 (95% CI 1.06-1.57) and to
      1.5 (95% CI 1.24-1.82) and the odds ratio for hypercholesterolemia decreased to
      0.8 (95% CI 0.62-0.95) and to 0.7 (95% CI 0.58-0.89); with regard to women,
      living in the same geographic areas the odds ratio for obesity increased to 1.3
      (95% CI 1.03-1.65) and to 2.3 (95% CI 1.81-2.83). CONCLUSIONS: In primary
      prevention it is important to focus the attention on obesity and on smoking
      habits among the poorer social classes.

PMID- 11307788
TI  - [Hypersensitivity to oral anticoagulants: report of a case].
AB  - We report a case regarding a 71 year-old Caucasian man with NYHA functional class
      III congestive heart failure, who was under warfarin treatment due to left
      ventricular thrombosis. After a few days, although the drug was not overdosed,
      the INR increased up to 11.68. Normal values were reestablished only after a 20
      day pharmacological wash-out. Surprisingly, no episode of major or minor bleeding
      occurred. Gene typing of cytochrome P450 CYP2C9, a liver enzyme responsible for
      warfarin metabolism, showed that the patient was a carrier of both the mutant
      alleles (CYP2C9*2/*3) of this enzyme. This genetic defect caused a reduced
      catabolism of S-warfarin and excessive anticoagulation.

PMID- 11307789
TI  - [Supravalvular aortic stenosis. Report of 3 cases].
AB  - In the following article three cases of supravalvular aortic stenosis are
      presented: the first two cases refer to two brothers. The older, a 22-year-old
      man presenting with palpitations, underwent echocardiography and Doppler that
      showed an hour-glass supravalvular aortic stenosis with a peak gradient of 115
      mmHg, associated with dilation of the left main coronary artery and stenosis of
      the left carotid artery at its origin. The patient's family was evaluated by
      echocardiography, and an 18-year-old brother was similarly found to have an hour
      glass supravalvular aortic stenosis, graded mild to moderate (peak gradient 40
      mmHg). Both cases are probably familiar forms of supravalvular aortic stenosis
      with normal facies and intelligence (autosomal dominant transmission). The elder
      brother, with severe stenosis, underwent surgical replacement of the ascending
      aorta. The third patient was a 23-year-old woman with a previous diagnosis of
      congenital aortic stenosis. Her characteristic elfic facies induced us to suspect
      the syndrome of Williams-Beuren; transthoracic and transesophageal
      echocardiographic examination showed an hour-glass supravalvular aortic stenosis
      with a peak gradient of 60 mmHg. Magnetic resonance imaging showed hypoplasia of
      the descending aorta and the iliac arteries. Since she was asymptomatic and
      presented only with a moderate gradient, the patient was not referred to surgical
      therapy. In this manuscript we present the three cases and review the
      histopathological, clinical, genetic, diagnostic and therapeutic aspects of this
      disease and its natural history.

PMID- 11307790
TI  - [Heart rupture during pre-discharge stress test after myocardial infarction].
AB  - A 65-year-old man with a postero-lateral myocardial infarction, complicated by
      rapid atrial fibrillation was admitted to the Intensive Coronary Care Unit. He
      received thrombolytic treatment. Electrocardiography and laboratory analysis were
      suggestive of reperfusion; the rapid atrial fibrillation was converted to sinus
      rhythm using i.v. amiodarone. Two echocardiograms performed on days 1 and 6
      revealed hypokinesis of the postero-lateral wall and a mild reduction in the left
      ventricular ejection fraction. On day 7, after pharmacological wash-out, he was
      submitted to a bicycle exercise test: soon after the beginning of the 75 W step,
      the patient presented cardiac arrest due to electromechanical dissociation and
      hemopericardium. Despite prolonged cardiopulmonary resuscitation maneuvers and
      drainage of a few milliliters of pericardial blood, the patient did not survive.
      At autopsy, a huge clot filling the pericardial space was detected together with
      two linear 3 cm tears of the left ventricular lateral wall. The authors stress
      the possibility of unpredictable deaths during a pre-discharge exercise testing;
      good clinical judgment should therefore be used in deciding which patients should
      undergo this procedure and appropriate information about its potential risks
      should be given.

PMID- 11307791
TI  - [Effects of pravastatin in 3260 patients with unstable angina: results from the
      LIPID study].

PMID- 11307792
TI  - [Statins and the risk of dementia].

PMID- 11307793
TI  - [Rhythm or rate control in atrial fibrillation -- Pharmacological Intervention in
      Atrial Fibrillation (PIAF): a randomized trial].

PMID- 11307794
TI  - [Efficacy and safety of oral dofetilide in converting to and maintaining sinus
      rhythm in patients with chronic atrial fibrillation or atrial flutter].

PMID- 11307795
TI  - [Triggering of sudden death from cardiac causes by vigorous exertion].

PMID- 11307796
TI  - [The Doppler test].

PMID- 11307797
TI  - NF-kappa B may determine whether epithelial cell--microbial interactions in the
      intestine are hostile or friendly.

PMID- 11307798
TI  - Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene:
      a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood.
AB  - In this study of 118 children (median age 5.1 years; range 6 months to 17 years)
      with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were
      homozygous for the thermolabile variant of the methylenetetrahydrofolate
      reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference
      population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular
      disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared
      with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a
      significant (p<0.025) increment of plasma total homocysteine concentration in
      homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the
      t-MTHFR allele, and control children with no history of stroke. In four of 12
      homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised,
      compared with three of 38 of those who were negative or heterozygous (p=0.047; OR
      5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly
      more likely to have a recurrent event than those who were negative or
      heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42).
      These data suggest that homozygosity for the t-MTHFR allele is associated with
      raised homocysteine levels in children and is a risk factor for primary and
      secondary stroke and TIA.

PMID- 11307799
TI  - Tissue factor as a therapeutic target.

PMID- 11307800
TI  - Conventional fibrinolytic assays for the evaluation of patients with venous
      thrombosis: don't bother.

PMID- 11307801
TI  - Generation of a humanized, high affinity anti-tissue factor antibody for use as a
      novel antithrombotic therapeutic.
AB  - Blocking the cofactor function of human tissue factor may be beneficial in
      various coagulation-mediated diseases. The murine antibody D3 binds to the
      membrane proximal substrate interaction region of human tissue factor and blocks
      tissue factor function even in the presence of bound factor VIIa. The cloned
      murine D3 antibody was humanized and affinity matured by exchanging amino acids
      in the complementarity determining regions as well as in the antibody framework.
      The humanized antibody, D3H44, bound to tissue factor with a 100-fold increased
      affinity (KD 0.1 nM) as compared to the original murine and chimeric versions.
      Depending on the particular disease, different pharmacokinetic properties of the
      antibody may be required and, therefore, several antibody variants-- F(ab),
      F(ab')2, IgG2, IgG4 and IgG4b-were generated. In vitro, the humanized D3
      antibodies displayed potent inhibition of plasma clotting and tissue factor:
      factor VIIa-mediated activation of factors IX and X (e.g. D3H44-F(ab')2,
      IC50(F.X) 47 pM). In addition, D3H44-F(ab')2 completely prevented fibrin
      deposition in a human ex vivo thrombosis model under venous blood flow conditions
      (IC50 37 nM). The humanized D3 antibodies may be utilized for treatment of
      cardiovascular diseases which involve tissue factor activity, e.g. acute coronary
      syndrome and venous thrombosis.

PMID- 11307802
TI  - Fibrinolytic variables in patients with recurrent venous thrombosis: a
      prospective cohort study.
AB  - To determine whether fibrinolytic testing predicts recurrent venous thrombosis,
      we have performed a prospective cohort study in which 303 patients with a first
      episode of venous thromboembolism underwent comprehensive fibrinolytic testing
      while receiving oral anticoagulants, and after anticoagulants had been
      discontinued. They were then followed for up to 3 years for recurrent venous
      thrombosis. No systematic differences in the levels or activity of type 1
      plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or
      euglobulin clot lysis times were detected between patients who did, or did not,
      suffer recurrent thrombosis. There were also no differences in these variables
      when patients whose initial thrombosis was idiopathic were compared to patients
      whose thrombosis occurred in the setting of a known thrombotic risk factor. Based
      on these results, neither measuring fibrinolytic parameters in patients with
      venous thromboembolism, nor modification of treatment based on the results of
      such testing, are justified. Our study also confirms that patients with
      idiopathic venous thromboembolism have a high risk of recurrence.

PMID- 11307803
TI  - Platelet function inhibitors in the Year 2000.

PMID- 11307804
TI  - Open multicentre study of the P2T receptor antagonist AR-C69931MX assessing
      safety, tolerability and activity in patients with acute coronary syndromes.
AB  - Platelet aggregation is the central process in the pathophysiology of acute
      coronary syndromes. ADP contributes to thrombosis by activating platelets, and AR
      C69931MX is a specific antagonist of this process acting at the P2T receptor. At
      5 hospitals, 39 patients with unstable angina or non-Q wave myocardial
      infarction, who were receiving aspirin and heparin, were administered intravenous
      AR-C69931MX with stepped dose increments over 3 h to a plateau of either 2
      microg/kg/min for 21 h (Part 1; n = 12) or up to 69 h (Part 2; n = 13) or 4
      microg/kg/min for up to 69 h (Part 3: n = 14). Safety parameters, platelet
      aggregation (PA) induced by ADP 3 micromol/L (impedance aggregometry), bleeding
      time (BT) and plasma concentrations of AR-C69931XX were assessed. AR-C69931MX was
      well tolerated. 33 patients completed the study. There were no deaths at 30 days
      and no serious adverse events attributed to AR-C69931MX. Trivial bleeding (56%)
      was common. At 24 h, mean inhibition of PA was 96.0 +/- 8.6, 94.9 +/- 14.4 and
      98.7 +/- 2.1% and BT was 9.5 +/- 8.4, 14.0 +/- 9.7 and 16.0 +/- 11.1 min for
      Parts 1, 2 and 3 respectively. At 1 h post-infusion, mean inhibition of PA was
      36.2 +/- 39.2, 20.7 +/- 25.9 and 40.7 +/- 36.7% respectively. 90% patients had a
      plasma half-life for AR-C69931XX of <9 min. In conclusion, AR-C69931MX is a
      potent, short-acting platelet ADP receptor antagonist suitable for further
      studies as an antithrombotic agent.

PMID- 11307805
TI  - Coagulation factor XIII and cardiovascular disease in UK Asian patients
      undergoing coronary angiography.
AB  - Possession of the coagulation factor XIII Val34Leu (FXIIIVal34Leu) polymorphism
      is associated with protection against myocardial infarction (MI) in Caucasians,
      in the absence of features of insulin resistance. The role of this polymorphism
      in the UK Asian population, with its high prevalence of insulin resistance and
      ischaemic heart disease, is unknown. We investigated the frequency of genotypes
      at this polymorphism, and measures of circulating FXIII in a group of UK Asians
      attending for coronary angiography. Genotype at the FXIIIVal34Leu polymorphism
      was not associated with MI. FXIII B-subunit levels correlated with waist: hip
      ratio (r = 0.19, p <0.005), HbA1c (r = 0.18, p <0.05), fasting triglycerides (r =
      0.21, p <0.005), total cholesterol (r = 0.29, p <0.0005) and PAI-1 antigen (r =
      0.24, p <0.005). An association between FXIIIVal34Leu and FXIII cross-linking
      activity was confirmed in these subjects (one-way ANOVA p <0.0005). This evidence
      does not support the hypothesis that FXIIIVal34Leu is protective against MI in
      the UK Asian population. FXIII B-subunit levels are strongly linked to risk
      factors for cardiovascular disease, suggesting an underlying association with
      insulin resistance.

PMID- 11307806
TI  - Impact of apolipoprotein(a) isoform size heterogeneity on the lysine binding
      function of lipoprotein(a) in early onset coronary artery disease.
AB  - Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease.
      Unique to Lp(a) is the apoprotein, apo(a) which can vary from 250 to 800 kDa in
      molecular weight. Small isoforms are also associated with the risk of
      cardiovascular disease. The purpose of this study was to examine the association
      of Lp(a) concentration, apo(a) size, and Lp(a) lysine-binding site(s) (LBS)
      function in patients with early onset heart disease, and age-matched controls.
      Mean values of Lp(a) were significantly higher in the patients than for the age
      matched group. The smallest molecular weight isoform for each subject had
      significantly fewer kringles for the patients than the age-matched controls.
      There was a significant correlation between LBS activity and kringle number in
      the single-banded phenotypes of the patients, but not the controls. LBS activity
      was significantly higher in patients with small isoforms (< or =18 kringles)
      compared to controls. The odds ratio for coronary artery disease for high LBS
      activity and high Lp(a) concentration was 4.4 (p = 0.002) and for high LBS
      activity and small isoforms was 10.1 (p = 0.002). In the patients, Lp(a)
      concentration was higher, apo(a) size was smaller, and LBS activity higher in the
      small isoforms compared to the controls. This study suggests an association of
      high LBS activity in small isoforms of Lp(a) with disease in humans.

PMID- 11307807
TI  - Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and
      risk of bleeding. A Multicenter Inception Cohort Study.
AB  - Oral anticoagulants (OA) are the drug of choice for stroke prevention in patients
      with non-rheumatic atrial fibrillation (NRAF). This clear benefit/risk ratio
      comes from several randomized clinical trials (RCT) in which highly selected
      patients were strictly monitored. The aim of this study was to ascertain whether
      the safety of OA was also obtained outside the setting of clinical trials in
      consecutive patients starting treatment and routinely followed at Italian
      anticoagulation clinics. A total of 433 patients with NRAF were enrolled in the
      ISCOAT study and followed up for a mean of 1.4 years. Two patients (0.3% per
      year) suffered from a complete non-fatal ischemic stroke, 8 patients (1.3% per
      year) died of thrombosis-related vascular death, and 11 patients (11 events, 1.8%
      per year) suffered from major bleedings (2 fatal). Major bleeding occurred more
      frequently in patients >75 years of age (6 events, 5.1% per year) than in younger
      patients (5 events, 1.0% per year). The cumulative incidence of major bleeding in
      patients over 75 years of age (10.8%; 95% CI, 1.8-19.8) was significantly higher
      than in younger patients (2.8%; 95% CI, 0.3-5.3, p = 0.006). Major primary
      bleeding unrelated to organic lesions (7 patients, 1 male and 6 females) occurred
      in 5 elderly patients (>75 years old) with a cumulative incidence (9.6%; 95% CI
      0.8-18.4) significantly higher than in younger patients (1.2%; 95% CI, 0-3.0, p =
      0.0003). Univariate analysis revealed a higher frequency of major primary
      bleeding in females, in diabetic patients and in in those who had suffered a
      previous thromboembolic event. Multivariate analysis revealed that only age
      grater than 75 years was independently related to major primary bleedings (RR
      6.6; 95% CI 1.2-37, p = 0.032). Minor bleedings (n = 27) were not more frequent
      in elderly patients (6% vs 4% per year, p = ns). Patients were kept at optimal
      intensity of treatment for 63% of the time. These data confirm the efficacy of OA
      but identify elderly patients as a high risk group of major bleeding.

PMID- 11307808
TI  - P-selectin antagonism causes dose-dependent venous thrombosis inhibition.
AB  - Inhibition of P-selectin by antibody or selectin antagonist decreases
      inflammation and thrombosis. This study evaluates the dose-response relationship
      using a selectin receptor antagonist. Eight male baboons (Papio anubis) underwent
      inferior vena caval thrombosis using a 6 h balloon occlusion model. Three animals
      received 500 microg/kg P-selectin antagonist (rPSGL-Ig) and five 1 mg/kg rPSGL-Ig
      with or without a non-anticoagulant dose of Dalteparin. These animals were
      compared to our published results in this model with 4 saline controls and 8
      animals that received 4 mg/kg rPSGL-Ig. A statistically significant dose-response
      relationship existed between rPSGL-Ig dose and thrombosis (p < 0.01), and between
      rPSGL-Ig dose and spontaneous recanalization (p<0.05). Inflammatory assessment
      revealed decreased gadolinium enhancement in all rPSGL-Ig groups compared to
      previously reported control, despite no significant differences in inflammatory
      cell extravasation. No dose of rPSGL-Ig caused anticoagulation. Selectin
      antagonism results in a dose-dependent decrease in thrombosis and increase in
      spontaneous recanalization.

PMID- 11307809
TI  - The incidence of deep venous thrombosis and pulmonary embolism among patients
      with inflammatory bowel disease:  a population-based cohort study.
AB  - BACKGROUND: There is an impression mostly from specialty clinics that patients
      with inflammatory bowel disease (IBD) have an increased risk of venous
      thromboembolic disorders. Our aim was to determine the incidence of deep venous
      thrombosis (DVT) and pulmonary embolism (PE) from a population-based database of
      IBD patients and, to compare the incidence rates to that of an age, gender and
      geographically matched population control group. METHODS: IBD patients identified
      from the administrative claims data of the universal provincial insurance plan of
      Manitoba were matched 1:10 to randomly selected members of the general population
      without IBD by year, age, gender, and postal area of residence using Manitoba
      Health's population registry. The incidence of hospitalization for DVT and PE was
      calculated from hospital discharge abstracts using ICD-9-CM codes 451.1, 453.x
      for DVT and 415.1x for PE. Rates were calculated based on person-years of follow
      up for 1984-1997. Comparisons to the population cohort yielded age-adjusted
      incidence rate ratios (IRR). Rates were calculated based on person-years of
      follow-up (Crohn's disease = 21,340, ulcerative colitis = 19,665) for 1984-1997.
      RESULTS: In Crohn's disease the incidence rate of DVT was 31.4/10,000 person
      years and of PE was 10.3/10,000 person-years. In ulcerative colitis the incidence
      rates were 30.0/10,000 person-years for DVT and 19.8/10,000 person-years for PE.
      The IRR was 4.7 (95% CI, 3.5-6.3) for DVT and 2.9 (1.8-4.7) for PE in Crohn's
      disease and 2.8 (2.1-3.7) for DVT and 3.6 (2.5-5.2) for PE, in ulcerative
      colitis. There were no gender differences for IRR. The highest rates of DVT and
      PE were seen among patients over 60 years old; however the highest IRR for these
      events were among patients less than 40 years. CONCLUSION: IBD patients have a
      threefold increased risk of developing DVT or PE.

PMID- 11307810
TI  - Interpreting the International Normalized Ratio (INR) in individuals receiving
      argatroban and warfarin.
AB  - The effects of argatroban, a direct thrombin inhibitor, on the International
      Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and
      functional factor X during warfarin co-administration were established to provide
      means to interpret INRs during argatroban/warfarin co-therapy. Twenty-four
      subjects receiving warfarin (7.5 mg, day 1; 3-6 mg/day, days 2-10) and argatroban
      (1-4 microg/kg/min over 5 h, days 1-11) were assessed daily for these coagulation
      parameters prior to argatroban infusion (warfarin "monotherapy") and at its
      conclusion ("co-therapy"). Argatroban increased aPTTs dose-dependently. Co
      therapy INR increased linearly with monotherapy INR, with slope sensitive to
      argatroban dose and thromboplastin used. Prediction errors for monotherapy INRs
      were < or =+/- 0.4 for argatroban 1-2 microg/kg/min but > or = +/-1.0 for higher
      doses. Despite co-therapy INRs >7, no major bleeding occurred. Factor X remained
      > or =37% of normal. Therefore, the predictable effect of argatroban (< or =2
      microg/kg/min only) [corrected] on INRs during warfarin co-therapy allows for
      reliable prediction of the level of oral anticoagulation.

PMID- 11307811
TI  - Pulmonary fibrosis is increased in mice carrying the factor V Leiden mutation
      following bleomycin injury.
AB  - Increased fibrin deposition following inflammatory lung injury has been proposed
      to facilitate the development of pulmonary fibrosis. Therefore, factors
      predisposing to thrombosis may affect the fibrotic response to injury. Activated
      protein C (aPC) resistance due to the factor V Leiden mutation (FvL) is a common
      genetic risk factor for vascular thrombosis. To examine the relationship between
      aPC resistance and the development of pulmonary fibrosis, lung inflammation was
      induced by bleomycin in mice carrying the FvL mutation. Three weeks following the
      instillation of 0.0375 U of bleomycin, the lungs of mice homozygous and
      heterozygous for FvL contained significantly more hydroxyproline (35 +/- 4 and 36
      +/- 7 ug hydroxyproline/mg total protein, respectively) than wild-type mice (26
      +/- 6 ug/mg protein, p <0.01 for both comparisons). These data demonstrate a
      strong relationship between aPC resistance and the pulmonary fibrosis that occurs
      following inflammatory lung injury.

PMID- 11307812
TI  - Intratracheal administration of recombinant human factor IX (BeneFix) achieves
      therapeutic levels in hemophilia B dogs.
AB  - The purpose of this paper was to establish proof of concept for administration of
      human recombinant F.IX (rF.IX) by inhalation for therapy of hemophilia B. The
      pharmacokinetics of intratracheal (IT) administration of rF.IX was studied in
      nine hemophilia B dogs randomized into 3 groups that received 200 IU/kg IT, 1,000
      IU/kg IT, or 200 IU/kg intravenously (IV). IT rF.IX produced therapeutic levels
      of F.IX antigen and activity and the pharmacokinetic parameters were consistent
      with a slow release from a depot site within the lungs. Bioavailability compared
      to IV administration was 11% for 200 IU/kg IT and 4.9% for 1,000 IU/kg. The whole
      blood clotting time began to shorten at 2 h but F.IX bioactivity was not detected
      until 8 h post infusion in both IT groups. In all groups, F.IX activity was
      detected through 72 h post administration. These data demonstrate that
      biologically active rF.IX can reach the systemic circulation when given IT.
      Aerosolization of rF.IX may provide a needle-free therapeutic option for delivery
      of rF.IX to hemophilia B patients.

PMID- 11307813
TI  - Hypofibrinogenemia due to novel 316 Asp --> Tyr substitution in the fibrinogen
      Bbeta chain.
AB  - We investigated the molecular basis of hypofibrinogenemia in a woman with a
      plasma fibrinogen of 1.0 mg/mL. After sequencing the coding region and intronic
      boundaries of all three fibrinogen genes a single heterozygous GAC-->TAC mutation
      was identified at codon 316 of the Bbeta gene. This Asp-->Tyr substitution
      segregated with the hypofibrinogenemia in the only other affected family member.
      Examination by SDS-PAGE, isoelectric focussing, reverse phase chromatography and
      electrospray ionisation (ESI) mass spectrometery, failed to detect expression of
      the new Bbeta chain in purified plasma fibrinogen. The absence of the variant
      chain was confirmed by ESI tryptic mapping; while the [M + 1 H] and [M + 2 H]
      ions of the affected peptide (MGPTELLIEMEDWK) were clearly visible at 1,692 and
      847 m/z, there were no new signals (1,741 or 871 m/z) that would at indicate
      expression of the variant in plasma. Asp 316 and its gamma chain homologue (Asp
      252) are conserved in all known species and this is the first report of a
      mutation at either of these. The residue appears to be critical in maintaining
      the structure of the five stranded sheet that forms the dominant structural
      feature of the D domains.

PMID- 11307814
TI  - Genetic predisposition to bleeding during oral anticoagulant therapy: evidence
      for common founder mutations (FIXVal-10 and FIXThr-10) and an independent CpG
      hotspot mutation (FIXThr-10).
AB  - The recent discovery of five patients with coumarin sensitive FIX-variants due to
      a missense mutation in the FIX propeptide, either Ala-10Val or Ala-10Thr, has
      highlighted a novel type of genetic predisposition to bleeding during oral
      anticoagulant therapy (OAT). In the present study, we report six additional
      patients with such FIX variants. Haplotype analysis of FIX polymorphisms revealed
      a founder effect in the five German and Swiss patients with the Val-10 variant.
      Also, four Thr-10 variants detected in Germany, Switzerland and Great Britain
      derived from a common founder. Two Thr-10 variants from USA showed an independent
      de novo origin at a CpG dinucleotide that in general represents a mutation
      hotspot. These findings implicate the existence of additional subjects with
      corresponding variants in the populations of various countries. Even though the
      rare occurrence of these variants does not justify a general aPTT screening
      during OAT, it is recommended to monitor each bleeding event during OAT in males
      in order to exclude a genetic predisposition to bleeding by means of the
      following testing strategy: a) aPTT-testing in each bleeding complication of male
      patients during OAT, b) if aPTT is disproportionately prolonged, determination of
      FIX:C, and c) if FIX:C is disproportionately decreased as compared to FII:C,
      FVII:C and FX:C, sequencing of exon 2 of the FIX gene. This strategy will provide
      a cost-effective and safe procedure to identify patients that carry the FIX
      variants. Moreover, such a strategy accumulates data about the prevalence of
      these FIX mutations in a given population.

PMID- 11307815
TI  - The role of catalytic cleft and exosite residues of factor VIIa for complex
      formation with tissue factor pathway inhibitor.
AB  - The extrinsic coagulation pathway is initiated by the binding of plasma factor
      VIIa (VIIa) to the cell surface receptor tissue factor (TF). Formation of the TF
      VIIa complex results in allosteric activation of VIIa as well as the creation of
      an extended macromolecular substrate binding exosite that greatly enhances
      proteolytic activation of substrate factor X. The catalytic function of the TF
      VIIa complex is regulated by a specific Kunitz-type inhibitor, tissue factor
      pathway inhibitor (TFPI). TFPI inhibition of the TF-VIIa complex was enhanced by
      the presence of Xa. This study investigates the relative contribution of
      catalytic cleft and exosite residues in VIIa for inhibitory complex formation
      with TFPI. VIIa protease domain residues Q176, T239 and E296 are involved in the
      formation of stable inhibitor complex with free TFPI. Kinetic analysis further
      demonstrated a predominant role of the S2' subsite residue Q176 for the initial
      complex formation with TFPI. In contrast, no significant reductions in inhibition
      by TFPI-Xa were found for each of the mutants in complex with phospholipid
      reconstituted TF. However, reduced rates of inhibition of the VIIa Gla-domain
      (R36) and Q176 mutant by TFPI-Xa were evident when TF was solubilized by
      detergent micelles. These data demonstrate docking of the TFPI-Xa complex with
      the macromolecular substrate exosite and the catalytic cleft, in particular the
      S2' subsite. The masking of the mutational effect by the presence of phospholipid
      shows a critical importance of Xa Gla-domain interactions in stabilizing the
      quaternary TF-VIIa-Xa-TFPI complex.

PMID- 11307816
TI  - Depletion of plasma factor XIII prevents disseminated intravascular coagulation
      induced organ damage.
AB  - The impact of clot stability affecting the vasculopathy and tissue necrosis in
      Shwartzman reaction was investigated using plasma Factor XIII A2-depleted rabbit
      (FXIII-DR). Plasma Factor XIIIA2 (FXIIIA2) was depleted by infusion of the mono
      specific goat anti-rabbit FXIIIA2 IgG. Generalized Shwartzman reaction (GSR) was
      induced by priming and challenged by i.v. injection of LPS and local Shwartzman
      reaction (LSR) was primed by intradermal injection of LPS and challenged by i.v.
      injection of LPS. Histological examination of the GSR animals showed, extensive
      thrombi accumulation in renal tubules and bilateral cortical necrosis of kidney
      in 8 out of 10 rabbits but none in the FXIII-DR. Fibrinogen levels were elevated
      to 3 approximately 4 fold at 24 h and lowered at 48 h whereas a steady rise was
      seen in the FXIII-DR. FDP levels in GSR animals were significantly elevated at 24
      h and further increased at 48 h but only slightly elevated in the FXIII-DR.
      Examination of the LSR tissues after 48 h showed an acute onset of progressive
      cutaneous vascular thrombosis, purpura, and secondary hemorrhagic necrosis
      whereas neither fibrin deposit nor necrosis of tissue were detected in FXIII-DR
      despite of an early edema formation. Fibrinogen levels were also increased two
      fold at 24 h but returned to basal levels at 48 h in control LSR animals but not
      affected at all in FXIII-DR. These results suggest that during the severe
      inflammatory conditions such as sepsis, the fibrinolytic system is functionally
      sufficient to dissipate the pathogenic accumulation of disseminated intravascular
      clots and exudated fibrin clots if those clots were prevented from getting
      crosslinked in plasma.

PMID- 11307817
TI  - The amino acid sequence in fibrin responsible for high affinity thrombin binding.
AB  - Human fibrin has a low affinity thrombin binding site in its E domain and a high
      affinity binding site in the carboxy-terminal region of its variant gamma' chain
      (gamma'408-427). Comparison of the gamma' amino acid sequence
      (VRPEHPAETEYDSLYPEDDL) with other protein sequences known to bind to thrombin
      exosites such as those in GPIbalpha, the platelet thrombin receptor,
      thrombomodulin, and hirudin suggests no homology or consensus sequences, but Glu
      and Asp enrichment are common to all. Tyrosine sulfation in these sequences
      enhances thrombin exosite binding, but this has not been uniformly investigated.
      The fibrinogen gamma' chain mass determined by electrospray ionization mass
      spectrometry, was 50,549 Da, a value 151 Da greater than predicted from its amino
      acid/carbohydrate sequence. Since each sulfate group increases mass by 80 Da,
      this indicates that both tyrosines at 418 and 422 are sulfated. A series of
      overlapping gamma' peptides was prepared for evaluation of their inhibition of
      125I-labeled PPACK-thrombin binding to fibrin. gamma'414-427 was as effective an
      inhibitor as gamma'408-427 and its binding affinity was dependent on all carboxy
      terminal residues. Mono Tyr-sulfated peptides were prepared by substituting non
      sulfatable Phe for Tyr at gamma'418 or 422. Sulfation at either Tyr residue
      increased binding competition compared with non-sulfated peptides, but was less
      effective than doubly sulfated peptides, which had 4 to 8-fold greater affinity.
      The reverse gamma' peptide or the forward sequence with repositioned Tyr residues
      did not compete well for thrombin binding, indicating that the positions of
      charged residues are important for thrombin binding affinity.

PMID- 11307818
TI  - Inhibition of arterial thrombosis by a soluble tissue factor mutant and active
      site-blocked factors IXa and Xa in the guinea pig.
AB  - The substrate recognition region of tissue factor contains two residues, Lys165
      and Lys166, which are important for macromolecular substrate activation by the
      tissue factor:factor VIIa complex. Replacement of these two residues with alanine
      in a soluble version of human tissue factor resulted in a mutant, hTFAA, which
      can bind factor VIIa but forms an enzymatically inactive complex. We found that
      hTFAA inhibits the activity of guinea pig factor VIIa, allowing us to evaluate
      hTFAA's effects on thrombosis and hemostasis in a guinea pig model of recurrent
      arterial thrombosis. In addition to heparin, the effects of hTFAA were compared
      to active site inhibited factor IXa (F.IXai) and factor Xa (F.Xai). We found that
      hTFAA, F.IXai and F.Xai were potent antithrombotics and may possess a decreased
      risk of hemorrhage when compared to unfractionated heparin. When administered at
      a dose that inhibited thrombosis by about 90%, hTFAA neither affected cuticle
      bleeding nor the activated partial thromboplastin time, and had only a modest
      effect on the prothrombin time. At equi-efficacious doses, F.IXai, F.Xai and
      heparin prolonged bleeding times by 20% (p >0.5), 50% (p <0.05) and 100% (p
      <0.01), respectively. In summary, our study demonstrates that, unlike heparin,
      specific inhibitors of factors VIIa, IXa and Xa can produce antithrombotic
      effects without or with only minimally disturbing normal hemostasis. The results
      further suggest that factor VIIa and factor IXa are especially promising targets
      for antithrombotic drug development.

PMID- 11307819
TI  - Novel design of peptides to reverse the anticoagulant activities of heparin and
      other glycosaminoglycans.
AB  - Patients undergoing anticoagulation with unfractionated heparin, low molecular
      weight heparin, or danaparoid may experience excess bleeding which requires
      reversal of the anticoagulant agent. Protamine is at present the only agent
      available for reversal of unfractionated heparin. Protamine is not effective in
      patients who have received low molecular weight heparin or danaparoid. We have
      developed a series of peptides based on consensus heparin binding sequences
      (Verrecchio et al., J Biol Chem 2000; 275: 7701-7707) that are capable of
      neutralizing the anti-thrombin activity of unfractionated heparin in vitro, the
      antifactor Xa activity of unfractionated heparin, Enoxaparin (Lovenox) and
      danaparoid (Orgaran) in vitro and the anti-Factor Xa activity of Enoxaparin in
      vivo in rats. These peptides may serve as alternatives for Protamine reversal of
      UFH and may be useful for neutralization of enoxaparin and danaparoid in humans.

PMID- 11307820
TI  - Antithrombotic effects of ionic and non-ionic contrast media in nonhuman
      primates.
AB  - Thromboembolic complications have been attributed to the use of radiographic
      contrast media (CM) during interventional procedures for arterial
      revascularization. However, due to the low frequency of adverse events,
      comparisons between different CM have been difficult to perform, although it has
      been suggested that ionic (vs. non-ionic) CM may be associated with fewer
      thrombotic events. The present study was undertaken using well-characterized
      baboon thrombosis models in order to compare different CM under physiologically
      relevant and controlled conditions of blood flow, exposure time, and CM
      concentration. Three CM were studied: ioxaglate, iohexol, and iodixanol. CM were
      locally infused into the proximal segment of femoral arteriovenous shunts. Palmaz
      Schatz stents (4 mm i.d.) and expanded tubular segments (9 mm i.d.), which
      exhibited venous-type flow recirculation and stasis, were deployed into the
      shunts distally. Saline was infused in identical control studies. Blood flow was
      maintained at 100 ml/min. Thrombosis was measured over a blood exposure period of
      2 hours by gamma camera imaging of 111In-platelets and by gamma counting of
      deposited 125I-fibrin. CM concentrations within the flowfield were predicted
      using computational fluid dynamics. At infusion rates of 0.1 and 0.3 ml/min, the
      low-osmolar ionic CM ioxaglate reduced both platelet and fibrin deposition on the
      stents by 75-80% (p <0.005), while both iohexol and iodixanol reduced platelet
      deposition by 30-50% (p <0.05). In the regions of low shear flow, ioxaglate (0.3
      ml/min) also reduced platelet deposition significantly (by 52% vs. control
      results; p <0.05). Thus the three agents evaluated--ioxaglate, iohexol, and
      iodixanol--all produced anticoagulant and antiplatelet effects and were
      inherently antithrombotic in vivo. The most striking effects were seen with the
      low osmolarity, ionic contrast agent ioxaglate.

PMID- 11307821
TI  - Elevated plasma levels of crosslinked fibrinogen gamma-chain dimer indicate
      cancer-related fibrin deposition and fibrinolysis.
AB  - Cancer-related fibrin deposition and fibrinolysis were investigated by two
      dimensional gel electrophoresis of human solid tumor and effusion specimen in
      addition to plasma samples. Fibrinogen gamma-chain dimer indicating fibrin
      deposition and plasmin-generated fibrinogen beta-chain fragments were identified
      in various solid tumor types by amino acid sequencing, mass spectrometry analysis
      and Western blotting. In tumor-associated effusions, these techniques allowed to
      observe plasmin-generated fragments of fibrinogen alpha, beta and gamma-chains in
      addition to elevated levels of acute-phase proteins. Similar observations were
      made in case of inflammation-associated effusions. No fibrin degradation product
      was observed in plasma samples, however, high amounts of fibrinogen gamma-chain
      dimer crosslinked by transglutaminase were detected in plasma from tumor
      patients, but not in plasma from controls and patients suffering acute infections
      and/or inflammations. This finding demonstrated that high transglutaminase
      activity may be associated with cancer. The presented data indicate that the
      amount of crosslinked fibrinogen gamma-chain dimer in plasma may correlate with
      tumor-associated fibrin deposition. The tumor-biological relevance of this
      potential marker protein is discussed.

PMID- 11307822
TI  - Like fibrin, (DD)E, the major degradation product of crosslinked fibrin, protects
      plasmin from inhibition by alpha2-antiplasmin.
AB  - Plasmin generation is localized to the fibrin surface because tissue-type
      plasminogen activator (t-PA) and plasminogen bind to fibrin, an interaction that
      stimulates plasminogen activation over a hundred-fold. To ensure efficient
      fibrinolysis, plasmin bound to fibrin is protected from inhibition by alpha2
      antiplasmin. (DD)E, a major soluble degradation product of cross-linked fibrin
      that is a potent stimulator of t-PA, compromises the fibrin-specificity of t-PA
      by promoting systemic activation of plasminogen. In this study we investigated
      whether (DD)E also protects plasmin from inhibition by alpha2-antiplasmin,
      facilitating degradation of this soluble t-PA effector. (DD)E and fibrin reduce
      the rate of plasmin inhibition by alpha2-antiplasmin by 5- and 10-fold,
      respectively. Kringle-dependent binding of plasmin to (DD)E and fibrin, with Kd
      values of 52 and 410 nM, respectively, contributes to the protective effect. When
      (DD)E is extensively degraded by plasmin, yielding uncomplexed fragment E and
      (DD), protection of plasmin from inhibition by alpha2-antiplasmin is attenuated.
      These studies indicate that (DD)E-bound plasmin, whose generation reflects the
      ability of (DD)E to stimulate plasminogen activation by t-PA, has the capacity to
      degrade (DD)E by virtue of its resistance to inhibition. This provides a
      mechanism to limit the concentration of (DD)E and maintain the fibrin-specificity
      of t-PA.

PMID- 11307823
TI  - Contribution of platelet-derived factor Va to thrombin generation on immobilized
      collagen- and fibrinogen-adherent platelets.
AB  - Adhesion of platelets to immobilized collagen induces the expression of anionic
      phospholipids, e.g. phosphatidylserine (PS), in the outer leaflet of the plasma
      membrane of these platelets. In contrast, of the platelets that adhere to
      immobilized fibrinogen only a small sub-population representing 10 +/- 3% of the
      total population of the fibrinogen-adherent platelets has exposed PS as probed by
      annexin V binding. Although the presence of PS is thought to be critical for
      thrombin generation at the platelet surface, no information is available about
      the effect of this differential PS exposure on the ability of adherent platelets
      to support thrombin generation. Perfusion of the fibrinogen- or collagen-adherent
      platelets with solutions containing factor Xa and prothrombin resulted in
      thrombin generation that i) increased linear during the first perfusion minutes,
      ii) was about two-fold faster at collagen-adherent than at fibrinogen-adherent
      platelets and iii) was for more than 98% restricted to the surface of the
      adherent platelets. It appeared that the lower thrombin generating capacity of
      fibrinogen-adherent platelets is not due to a lower overall surface density of
      PS, but is caused by lower amounts of platelet-bound factor Va. Firstly, in both
      cases thrombin generation could be completely attenuated with antibodies against
      human factor Va, and secondly, in the presence of an excess of exogenous plasma
      derived factor Va similar initial rates of thrombin formation were measured for
      collagen- and fibrinogen-adherent platelets. Our findings suggest a unique role
      for immobilized collagen in maintaining haemostasis.

PMID- 11307824
TI  - Rho-kinase is involved in the sustained phosphorylation of myosin and the
      irreversible platelet aggregation induced by PAR1 activating peptide.
AB  - We have addressed the role of Rho-kinase in the different steps of thrombin
      receptor agonist peptide (TRAP)-induced platelet activation. Interestingly, under
      physiological conditions, incubation of platelets with increasing concentrations
      of the specific Rho-kinase inhibitor Y-27632 resulted in a dose-dependent
      reversion of the aggregation induced by 10 microM TRAP, without affecting
      serotonin secretion. Addition of Y-27632 after three minutes of TRAP stimulation,
      when the maximal aggregation was reached, resulted in a rapid disaggregation of
      platelets. Accordingly, the early peak of myosin light chain (MLC)
      phosphorylation induced by TRAP was not affected by Y-27632 but its sustained
      phosphorylation, observed during the irreversible phase of aggregation, was
      dependent of Rho-kinase activity. The rapid decrease in MLC phosphorylation upon
      Y-27632 treatment correlated well with the specific disappearance of myosin heavy
      chain from the cytoskeleton and preceded platelet disaggregation. Finally, we
      provide evidence that secreted ADP, known to play a key role in TRAP-induced
      irreversible phase of aggregation, was involved in the sustained MLC
      phosphorylation through Rho-kinase and could be replaced by epinephrine.

PMID- 11307825
TI  - Antiplatelet and antithrombotic activity of SL65.0472, a mixed 5-HT1B/5-HT2A
      receptor antagonist.
AB  - The antiplatelet and antithrombotic activity of SL65.0472 (7-fluoro-2-oxo-4-[2-[4
      (thieno [3,2-c]pyrin-4-yl) piperazin-1-yl]ethyl]-1,2-di-hydroquinoline
      acetamide), a mixed 5-HT1B/5-HT2A receptor antagonist was investigated on 5HT
      induced human platelet activation in vitro, and in rat, rabbit and canine
      platelet dependent thrombosis models. SL65.0472 inhibited 5-HT-induced platelet
      shape change in the presence of EDTA (IC50 values = 35, 69 and 225 nM in rabbit,
      rat and human platelet rich plasma (PRP)), and also inhibited aggregation induced
      in human PRP by 3-5 microM 5-HT + threshold concentrations of ADP (0.5-1 microM)
      or collagen (0.3 microg/ml) with mean IC50 values of 49 +/- 13 and 48 +/- 6 nM
      respectively. SL65.0472 inhibited thrombus formation when given both
      intravenously 5 min and orally 2 h prior to assembly of an arterio-venous (A-V)
      shunt in rats as from 0.1 and 0.3 mg/kg respectively. It was active in a rabbit A
      V shunt model with significant decreases in thrombus weight as from 0.1 mg/kg i.
      v. and at 10 mg/kg p.o. The delay to occlusion in an electric current-induced
      rabbit femoral artery thrombosis model was increased by 251% (p <0.05) after 20
      mg/kg p.o. SL65.0472 (30 microg/kg i.v.) virtually abolished coronary cyclic flow
      variations (7.2 +/- 1.0/h to 0.6 +/- 0.6/h, p <0.05) and increased minimum
      coronary blood flow (1.2 +/- 0.8 ml/min to 31.8 +/- 8.4 ml/min, p <0.05) in a
      coronary artery thrombosis model in the anaesthetised dog. Finally, SL65.0472
      significantly increased the amount of blood lost after rat tail transection at 3
      mg/kg p.o. Thus the anti-5-HT2A component of SL65.0472 is reflected by its
      ability to inhibit 5-HT-induced platelet activation, and platelet-rich thrombus
      formation.

PMID- 11307826
TI  - Targeted disruption of the mouse Gz-alpha gene: a role for Gz in platelet
      function?
AB  - Gz is one of nine G proteins identified in platelets and its role in these cells
      is unknown. Our laboratory has generated a mouse deficient in the Gz-alpha gene
      in the hope of determining its in vivo function. Bleeding times from the tail tip
      of Gzalpha deficient mice was significantly longer than wild type mice. Platelet
      aggregation and ATP secretion did not differ between wild type and Gzalpha
      deficient mice. When mice were presented with a thromboembolism challenge no
      differences were observed in the survival or mortality of wild type or Gzalpha
      deficient mice, however a strain difference was observed. Ignoring the genetic
      background of a mutant mouse might lead to a misinterpretation of results and
      thus it is absolutely critical to take the genetic background into account when
      assessing any aspect of a mutant mouse.

PMID- 11307827
TI  - Neutrophil proteases can inactivate human PAR3 and abolish the co-receptor
      function of PAR3 on murine platelets.
AB  - Three members of the protease-activated receptor family, PAR1, PAR3 and PAR4, are
      activated when thrombin cleaves the receptor N-terminus, exposing a tethered
      ligand. Proteases other than thrombin can also cleave PAR family members and,
      depending upon whether this exposes or removes the tethered ligand, either
      activate or disable the receptor. For example, on human platelets PAR1 is
      disabled by cathepsin G, although aggregation still occurs because cathepsin G
      can activate PAR4. The present studies examine the interaction of cathepsin G and
      a second neutrophil protease, elastase, with PAR3 using two model systems: COS-7
      cells transfected with human PAR3 and mouse platelets, which express PAR3 and
      PAR4, but not PAR1. In contrast to human platelets, cathepsin G did not aggregate
      murine platelets, and prevented their activation only at low thrombin
      concentrations. Elastase had no effect on thrombin responses in mouse platelets,
      but when added to COS cells expressing human PAR3, both cathepsin G and elastase
      prevented activation of phospholipase C by thrombin. Notably, this inhibition
      occurred without loss of the binding sites for two monoclonal antibodies that
      flank the tethered ligand on human PAR3. We therefore conclude that 1) exposure
      to cathepsin G disables signaling through human PAR3, and prevents murine PAR3
      from serving its normal role, which is to facilitate PAR4 cleavage at low
      thrombin concentrations, 2) elastase disables human, but not murine, PAR3, 3) in
      contrast to human PAR4, mouse PAR4 will not support platelet aggregation in
      response to cathepsin G, and 4) the inactivation of human PAR3 by cathepsin G and
      elastase involves a mechanism other than amputation of the tethered ligand
      domain. These results extend the range of possible interactions between PAR
      family members and proteases, and provide further support for species-specific
      differences in the interaction of these receptors with proteases other than
      thrombin.

PMID- 11307828
TI  - Effect of Ca2+ chelation on the platelet inhibitory ability of the GPIIb/IIIa
      antagonists abciximab, eptifibatide and tirofiban.
AB  - OBJECTIVE: Enhanced GPIIb/IIIa binding and inhibition of platelet aggregation of
      eptifibatide by the reduction of ionized plasma calcium concentrations have been
      reported. The present study compared the importance of Ca2+ chelation on the in
      vitro platelet inhibitory profiles of the GPIIb/IIIa antagonists abciximab,
      eptifibatide and tirofiban. METHODS AND RESULTS: Turbidimetric platelet
      aggregation dose response curves of the various GPIIb/IIIa antagonists were
      performed using platelet rich plasma (PRP) anticoagulated with either trisodium
      citrate, or the non-chelating anticoagulant, PPACK. The concentrations of
      antagonist that resulted in 50% inhibition of TRAP-induced (10 microM) platelet
      aggregation (IC50) were measured in the presence of either citrate or PPACK. In
      addition, the influence of Ca2+ chelation on the binding properties (relative
      affinity, on- and off-rates) of abciximab for the GPIIb/IIIa receptor on
      platelets was measured. For all three agonists, the IC50 concentrations were
      lower for platelets treated with citrate than PPACK, but the degree of difference
      varied among the agents. The mean TRAP IC50 values for citrate and PPACK were
      88.2 +/- 12.2 nM and 126.1 +/- 28.4 nM for abciximab (1.4 fold enhancement; p =
      0.0007), 75.9 +/- 13.3 nM and 142.6 +/- 32.6 nM for tirofiban (1.9-fold
      enhancement; p = 0.001), and 260.2 +/- 62.5 nM and 810.3 +/- 182.5 nM for
      eptifibatide (3.1-fold enhancement; p = 0.001). A similar shift in effective
      inhibitor concentrations for abciximab was observed with ADP (10 microM). The
      relative affinities (EC50), on- and off-rates of abciximab for the platelet
      GPIIb/IIIa receptor in the presence of trisodium citrate and PPACK were
      equivalent. CONCLUSIONS: These data confirm previous observations that Ca2+
      chelation afforded by citrate decreases the effective inhibitor concentrations of
      GPIIb/IIIa antagonists, as assessed by turbidimetric platelet aggregation.
      However, the extent of decrease was less for abciximab and tirofiban, compared to
      eptifibatide.

PMID- 11307829
TI  - Factor XI assembly and activation on human umbilical vein endothelial cells in
      culture.
AB  - Biotin-FXI optimally bound to HUVEC in the presence of 40 nM high molecular
      weight kininogen (HK) and > or =7 microM Zn2+. There was little specific FXI
      binding in the absence of added HK and at concentrations of Zn2+ <15 microM. FXI
      and prekallikrein, but not prothrombin, blocked biotin-FXI binding to HUVEC in
      the presence of HK with an IC50 of 18 nM and 180 nM, respectively. Monoclonal
      antibody HKL16 and peptide SDD31 also inhibited biotin-XI binding in the presence
      of HK with an IC50 of 4.7 nM and 50 microM, respectively. Alternatively, peptide
      T249-F260 of FXI's apple domain 3 and heparin monosulfate were weak inhibitors of
      FXI binding to HUVEC. FXI bound to HUVEC with an apparent Kd of 6.9 +/- 3.0 nM
      and Bmax of 13 +/- 2.6 x 10(6) sites/cell. FXI bound to HK on HUVEC, but not
      prothrombin, became converted to FXIa. FXI activation on HUVEC resulted from
      tissue culture media bovine factor XIIa. HUVEC grown in human factor XI-deficient
      serum did not support FXI activation. FXI binding to HUVEC in culture was mostly
      mediated by HK and FXI activation on HUVEC is dependent on cell-associated factor
      XIIa.

PMID- 11307830
TI  - The subendothelium of the HMEC-1 cell line supports thrombus formation in the
      absence of von Willebrand factor and collagen types I, III and VI.
AB  - The macromolecular composition of the extracellular matrix (ECM) produced by the
      human microvascular endothelial cell line (HMEC-1) was determined by ELISA and
      its thrombogenicity was studied in blood perfusion assays. Results were compared
      with those obtained with the ECM produced by human umbilical vein endothelial
      cells (HUVEC). The HMEC-1's ECM contains collagen type IV, fibronectin, laminin
      and thrombospondin, but no detectable levels of collagen types I, III and VI, or
      von Willebrand factor (vWF), whereas all these components were found in the ECM
      synthesized by HUVEC. HMEC-1's ECM was perfused with low-molecular-weight heparin
      anticoagulated blood at two wall shear rates (650/s and 2,600/s), representative
      of moderate and high arterial wall shear rates, in parallel plate flow chambers
      for 5 min. This resulted in the formation of large platelet aggregates, compared
      to essentially a monolayer of adherent platelets on HUVEC's ECM. Interestingly,
      large thrombi were formed at 2,600/s when HMEC-1's ECM was perfused with the
      blood of a patient with severe type III von Willebrand disease lacking both
      plasma and platelet vWF, indicating that vWF was not absolutely required for
      thrombus formation on this matrix. Thrombin generated on the HMEC-1's ECM
      contributed importantly to the large platelet thrombi formed, shown by performing
      blood perfusion experiments in the presence of thrombin inhibitors. Our results
      indicate that 1) platelet adhesion and aggregate formation on a subendothelium
      may occur at a high shear rate (2600/s) without the participation of collagen
      types I, III and VI, and vWF; and 2) the HMEC-1 cell line may prove useful for in
      vitro studies of the thrombogenic properties of microvascular subendothelium
      which in most cases does not contain fibrillar collagens and vWF.

PMID- 11307831
TI  - Definitions in hemophilia. Recommendation of the scientific subcommittee on
      factor VIII and factor IX of the scientific and standardization committee of the
      International Society on Thrombosis and Haemostasis.

PMID- 11307832
TI  - Unexpected flow cytometric results with two small GPIIb/IIIa blockers:
      eptifibatide and tirofiban.

PMID- 11307833
TI  - Idiopathic deep vein thrombosis in siblings with homozygous factor V Leiden
      mutation.

PMID- 11307834
TI  - Feasibility of LMW heparin prophylaxis for management of thrombophilia
      investigation in patients on oral anticoagulation therapy.

PMID- 11307835
TI  - Nomograms for the administration of unfractionated heparin.

PMID- 11307836
TI  - No association between the R2 factor V gene and acute coronary events.

PMID- 11307837
TI  - Coagulation factor IX propeptide mutations causing coumarin hypersensitivity:
      identification of female alanine-10 valine heterozygotes.

PMID- 11307838
TI  - Factor XIII activity and antigen levels in patients with coronary artery disease.

PMID- 11307839
TI  - A novel nonsense mutation in the antithrombin III gene (Ser365 to stop) causing
      deep and mesenteric venous thromboses.

PMID- 11307840
TI  - Elevated expression of mitochondrial NADH dehydrogenase subunit 4/4L genes in
      vascular endothelial cells undergoing sphingosine-induced apoptosis.

PMID- 11307841
TI  - Stroke and platelet glycoprotein Ibalpha polymorphisms.

PMID- 11307842
TI  - Acute local release of fibroblast growth factor-2 but not transforming growth
      factor-beta1 following coronary stenting.

PMID- 11307843
TI  - The genus Gluconobacter and its applications in biotechnology.
AB  - Organisms of the genus Gluconobacter have been widely utilized within the
      biotechnology industry for many decades, due to their unique metabolic
      characteristics. The metabolic features that render Gluconobacter so useful in
      biotransformation processes, vitamin synthesis, and, as the biological element in
      sensor systems, are critically evaluated, and the relevance of recent biochemical
      genetic studies to current and future industrial Gluconobacter processes is
      discussed. The impact of recombinant gene technology on the status of
      Gluconobacter processes and the potential use of such techniques in clarifying
      aspects of the physiology of Gluconobacter is reviewed.

PMID- 11307844
TI  - Escherichia coli O157:H7 as an emerging foodborne pathogen: a literature review.

PMID- 11307845
TI  - Grain processing and nutrition.
AB  - Whole grains provide a wide range of nutrients and phytochemicals that optimize
      health. Epidemiologic studies support the protectiveness of whole grain
      consumption for cardiovascular disease and cancer. Dietary guidance endorses
      increased whole grains in our diet. A crucial question remaining is the effect of
      processing of whole grains on their content of nutrients and phytochemicals.
      Although processing is often considered to be a negative attribute in nutrition,
      and some forms of processing reduce nutritional value, many factors support the
      importance of processing of grains to enhance grain consumption. First, whole
      grains as harvested are generally not consumed directly by humans but require
      some processing prior to consumption. While refining, that is, removal of the
      bran and the germ, reduces the nutrient content of grain, milling of grains
      otherwise concentrates desirable grain components and removes poorly digested
      compounds and contaminants. Cooking of grains generally increases digestibility
      of nutrients and phytochemicals. Studies in both animal models and humans support
      the notion that processed grains are often nutritionally superior to unprocessed
      grains, probably because of enhanced nutrient bioavailability in processed
      grains. Processing of grains also provides shelf-stable products that are
      convenient and good tasting for consumers.

PMID- 11307846
TI  - pH-dependent actions of aluminum on voltage-activated sodium currents in snail
      neurons.
AB  - The pH-dependent actions of aluminum(III) hydroxides (Al(III))on the voltage
      activated sodium currents (VASCs) in the giant neurons of the pond snail Lymnaea
      stagnalis L. were studied by means of a conventional two-electrode voltage-clamp
      technique. The final concentration of Al(III) was 5-500 microM at pH 7.7, 6.9 or
      6.0. A significant and concentration-dependent increase in the peak amplitude of
      the VASCs was recorded over the entire voltage range at pH 7.7 (EC50 = 100.7 +/-
      33.7 microM, n = 9), without alteration of the gating properties. A concentration
      dependent decrease in the peak amplitude (IC50 = 175.9 +/- 73.6 microM, n = 6)
      and concomitant increases in the time constants of activation and inactivation of
      the VASCs were recorded in slightly acidic media (pH 6.0), whereas there were no
      changes in the investigated parameters at pH 6.9. A significant increase in the
      V1/2 of the half-maximal current of the steady-state inactivation resulted on
      Al(III) application at pH 7.7, but not at pH 6.9 or 6.0. These results suggest
      that Al(III) can differentially up- and down-modulate the sodium current and
      related physiological functions to extents dependent on the pH-determined
      speciation of the Al(III) hydroxides present.

PMID- 11307847
TI  - Effects of thienylphencyclidine (TCP) on seizure activity and brain damage
      produced by soman in guinea-pigs: ECoG correlates of neurotoxicity.
AB  - The capacity of thienylcyclohexylpiperidine (TCP), a non-competitive blocker of
      the N-methyl-D-aspartate (NMDA) receptor, to counteract the convulsant, lethal,
      and neuropathological effects of 2 x LD50 of soman (an irreversible inhibitor of
      cholinesterase) was investigated in guinea-pigs treated by pyridostigmine and
      atropine sulphate. The effects of a weak dose of TCP (1 mg/kg) used in the
      present study globally reproduced those previously obtained with a higher dose
      (2.5 mg/kg; [Neurotoxicology 15 (1994) 837]): TCP was again most protective when
      given curatively within the first hour of soman-induced seizures. In this
      condition, (a) paroxysmal activity ceased in 10-20 min, (b) all the animals
      survived, (c) the majority of them recovered remarkably well and did not show any
      brain damage 24 h after the intoxication, and (d) the minimal duration of seizure
      activity normally required for producing soman-induced brain damage in other
      pharmacological environments was increased from 10 to 40 min to 80 min.
      Strikingly, when TCP was given 120 min after seizure onset, it failed to show any
      anticonvulsant activity but still provided neuroprotection in the hippocampus.
      The present study also gives additional evidence (see [Neurotoxicology 21 (4)
      (2000) 521]) that in soman poisoning, (a) the development of brain damage depends
      on the occurrence of ECoG seizures, (b) the topographical distribution of lesions
      depends on seizure duration, and (c) an increase of the relative power in the
      lowest (delta) frequency band might be a reliable marker of neuronal degradation.
      All these findings confirm that (a) glutamatergic NMDA receptors are involved in
      the mechanisms of soman-induced seizures and brain damage, (b) non-competitive
      antagonists of NMDA receptors might be promising candidates for post-treatment of
      soman poisoning, and (c) ECoG parameters from ECoG tracings and power spectrum
      might serve as useful external predictors for soman-induced neuropathological
      changes.

PMID- 11307849
TI  - Acute toxicity screening of novel AChE inhibitors using neuronal networks on
      microelectrode arrays.
AB  - Spontaneously active neuronal networks grown from embryonic murine frontal cortex
      on substrate integrated electrode arrays with 64 recording sites were used to
      assess acute neurobiological and toxic effects of a series of seven symmetrical,
      bifunctional alkylene-linked bis-thiocarbonate compounds designed to possess
      anticholinesterase activity. Acute functional neurotoxicity in the absence of
      cytotoxicity was defined as total collapse of spontaneous activity. All of the
      compounds were characterized as mixed inhibitors of AChE, with K(i)'s in the 10(
      7)-10(-6) M range. The neuronal network assays revealed high repeatability for
      each compound, but surprisingly diverse effects among these closely related
      compounds. Six of the seven compounds produced changes in network activity at
      concentrations of 10-350 microM. Three of the compounds were excitatory, two were
      biphasic (excitatory at lower concentrations, inhibitory at higher), and one was
      solely inhibitory. Two of the inhibitory compounds produced irreversible
      inhibition of activity. Responses of cortical cultures to eserine were compared
      to the effects produced by the test compounds, with only one of seven providing a
      close match to the eserine profile. Matching of response patterns allows the
      classification of new drugs according to their response similarity to well
      characterized agents. Spontaneously active neuronal networks reflect the
      interactions of multiple neurotransmitter and receptor systems, and can reveal
      unexpected side effects due to secondary binding. Utilizing such networks holds
      the promise of greater research efficiency through a more rapid recognition of
      physiological tissue responses.

PMID- 11307848
TI  - Effects of Huperzine used as pre-treatment against soman-induced seizures.
AB  - Huperzine A (HUP), an alkaloid isolated from the Chinese club moss, Huperzia
      serrata is a reversible inhibitor of cholinesterases which crosses the blood
      brain barrier and shows high specificity for acetylcholinesterase (AChE) and a
      prolonged biological half-life. We tested, in vivo, its efficiency in protecting
      cortical AChE from soman inhibition and preventing subsequent seizures. The
      release of acetylcholine (ACh) was also followed in the cortex of freely moving
      rats using microdialysis techniques. We previously found that soman-induced
      seizures occurred in rodents only when the cortical AChE inhibition was over 65%
      and when the increase of ACh level was over 200 times the baseline level. This
      was verified in the present study in control animals intoxicated by 1 LD50 of
      soman (90 microg/kg). Using the same dose of soman in rats pre-treated with 500
      microg/kg of HUP, we observed that 93% of the animals survived and none of them
      had seizures. This dose of HUP reduced AChE inhibition to 54% and increase of ACh
      level to 230 times baseline value. HUP thus appears as a promising compound to
      protect subjects against organophosphorus intoxication.

PMID- 11307850
TI  - Age-related effects of chlorpyrifos on acetylcholine release in rat brain.
AB  - Chlorpyrifos (CPF) is an organophosphorus insecticide that elicits toxicity
      through inhibition of acetylcholinesterase (AChE). Young animals are markedly
      more sensitive than adults to the acute toxicity of CPF. We evaluated
      acetylcholine (ACh) release and its muscarinic receptor-mediated regulation (i.e.
      muscarinic autoreceptor function, MAF) during maturation as a possible
      contributing factor to age-related differences in sensitivity. Cortical and
      striatal slices were prelabeled with [3H]choline chloride, superfused in the
      presence or absence of the anticholinesterase physostigmine (PHY, 20 microM) and
      stimulated twice (S1 and S2) with a high concentration of potassium chloride (20
      mM). Depolarization-stimulated ACh release (DSAR) was lowest in neonatal,
      intermediate in juvenile and markedly higher in adult tissues. MAF was not
      detectable in tissues from neonatal rats but was present in juvenile and adult
      tissues. ACh release and MAF were studied at 4, 24 and 96 h following oral
      exposure to CPF (0, 0.5 or 1 x LD10). In general, 40-60% and 80-90% maximal AChE
      inhibition followed exposure to the respective 0.5 and 1 x LD10 dosages. DSAR was
      decreased in neonatal cortex 1 day after LD10 exposure but increased in juvenile
      striatum 1 day after LD10 treatment. In adults, DSAR was reduced at 4 and 24 h
      after exposure, but increased 96 h after CPF exposure. In juveniles, MAF was
      reduced in both brain regions at 24 h after 0.5LD10 exposure and at 24 and 96 h
      after LD10 exposure in cortex. A later reduction in MAF was noted in adult
      tissues (i.e. only at 96 h after LD10 treatment). Together, the results suggest
      that ACh release dynamics in brain vary markedly during postnatal maturation and
      that acute CPF exposure can alter ACh release in an age-related manner. The
      functional status of presynaptic processes regulating neurotransmitter release
      may contribute to age-related neurotoxicity elicited by high-dose exposures to
      chlorpyrifos.

PMID- 11307851
TI  - Lead exposure in pheochromocytoma (PC12) cells alters neural differentiation and
      Sp1 DNA-binding.
AB  - Previous studies have revealed that lead modulates the DNA-binding profile of the
      transcription factor Sp1 both in vivo and in vitro (Dev Brain Res 1998;107:291).
      Sp1 is a zinc finger protein, that is selectively up-regulated in certain
      developing cell types and plays a regulatory role during development and
      differentiation (Mol Cell Biol 1991;11:2189). In NGF-stimulated PC12 cells, Sp1
      DNA-binding activity was induced within 48 h of exposure of NGF naive cells.
      Exposure of undifferentiated PC12 cells to lead alone (0.1 microM) also produced
      a similar increase in Sp1 DNA-binding. Since lead altered the DNA-binding profile
      of Sp1 in newly differentiating cells, neurite outgrowth was assessed as a
      morphological marker of differentiation to determine whether or not the effects
      of lead on differentiation were restricted to the initiation phase (unprimed) or
      the elaboration phase of this process (NGF-primed). NGF-primed and unprimed PC12
      cells were prepared for bioassay following exposure to various concentrations of
      NGF and/or lead. Neurite outgrowth was measured at 48 and 72 h during early
      stages of NGF-induced differentiation and at 14 h in NGF primed/replated cells.
      In the absence of NGF, exposure to lead alone (0.025, 0.05, 0.1 microM) promoted
      measurable neurite outgrowth in unprimed PC12 cells at 48 and 72 h. A similar
      phenomenon was also observed in primed/replated PC12 cells at 14 h. However, this
      effect was two to five times greater than unprimed control cells. In the presence
      of NGF, a similar trend was apparent at lower concentrations, although the
      magnitude and temporal nature was different from lead alone. In most cases, the
      administration of higher lead concentrations (1 and 10 microM), in both the
      absence or presence of NGF, was less effective than the lower concentrations in
      potentiating neurite outgrowth. These results suggest that lead alone at low
      doses may initiate premature stimulation of morphological differentiation that
      may be related to lead-induced alterations in Sp1 binding to DNA.

PMID- 11307852
TI  - Differential toxicity of aluminum salts in human cell lines of neural origin:
      implications for neurodegeneration.
AB  - Aluminum is highly oxophilic and its minerals are usually found surrounded by six
      oxygen atoms. A role for the metal has been established in dialysis
      encephalopathy and Al-induced osteomalacia. The metal has been implicated in
      Alzheimer's disease but the issue is at present controversial. Human cell lines
      of neural origin were utilized to study the effect of lipophilic aluminum
      acetylacetonate and non-lipophilic aluminum sulfate on cell proliferation and
      viability. Although analysis of Al species in the cell culture media demonstrated
      that there are positively charged Al species present in solutions prepared with
      both Al salts, only the aluminum acetylacetonate salt caused changes in cell
      proliferation and viability. Therefore, the lipophilic nature of the organic Al
      salt is a critical determinant of toxicity. The effect of aluminum
      acetylacetonate was dose-dependent and time-dependent. Neuroblastoma (SK-N-SH)
      cells were more susceptible to decreased cell proliferation although the
      lipophilic Al salt was more toxic to the glioblastoma (T98G) cells. While the
      toxicity of aluminum acetylacetonate was inhibited in the T98G cells by the
      addition of phosphate, the same treatment did not reverse cell death in the SK-N
      SH cells. Thus, the mechanism of Al toxicity appears to be different in the two
      cell lines. It is possible that the principal neurotoxic target of the metal is
      glial and when these cells are in a compromised state, this may secondarily
      impact the neuronal population and thus eventually lead to neurodegeneration.

PMID- 11307853
TI  - Effects of senescence and citral on neuronal vacuolar degeneration in rat pelvic
      ganglia.
AB  - A significant part of the morbidity in elderly men involves pelvic organs and
      their autonomic neural regulation. Environmental stimuli also impair the
      structure and function of pelvic organs. One of these factors is citral, a widely
      used cosmetic fragrance constituent, which causes severe prostatic hyperplasia in
      rats. In this study, we assessed the effect of topical administration of citral
      (30 days) on the morphology of pelvic ganglia (PG) in young adult and old Wistar
      rats. Neuronal vacuolar degeneration with preserved nuclei of PG neurons was
      observed in untreated senescent, but not young rats. Citral significantly
      increased the rate of vacuolated neurons in old rats (from 3 to 14%), but only
      slightly in young ones (from 0 to 0.5-0.3%). Similar lesions were not found in
      inferior cervical or celiac ganglia, in either group. This shows that
      environmental stimuli enhance age-related processes of vacuolar neuronal
      degeneration in PG, and may contribute to the dysfunction of pelvic organs in the
      elderly.

PMID- 11307854
TI  - Behavioral effects following subacute inhalation exposure to m-xylene or
      trimethylbenzene in the rat: a comparative study.
AB  - Trimethylbenzene (TMB), like xylene (dimethylbenzene), is a significant
      constituent of some industrial solvent mixtures. In earlier studies, we found
      that in the rat a subacute low-level inhalation exposure to some of the TMB
      isomers may result in behavioral alterations detectable weeks after the exposure
      [Neurotoxicol Teratol 19;1997:327; Int J Occup Med Environ Health 11;1998:319].
      The purpose of the present study was to compare m-xylene (XYL) and each of the
      TMB isomers: 1,2,3-TMB (hemimellitene - HM), 1,2,4-TMB (pseudocumene - PS), and
      1,3,5-TMB (mesitylene - MES) with respect to the ability for inducing behavioral
      effects in the rat. The rats (10-11 animals per group) were exposed repeatedly
      for 4 weeks (6 h per day, 5 days per week) to XYL (XYL group), HM (HM group), PS
      (PS group) or MES (MES group) at 100 ppm, or sham exposed (C group) in 1.3 cu/m
      dynamic inhalation chambers. Starting 2 weeks after exposure the following forms
      of rat's behavior were assessed: radial maze performance, spontaneous activity in
      an open field, learning and retention of passive and active (two-way) avoidance
      response, and heat-induced paw licking before and after a 2 min footshock (a test
      for assessment of the stress response). None of the solvent-exposed groups
      differed considerably from the control one with respect to the radial maze
      performance. Compared to control rats, the rats of the XYL, PS and MES groups,
      but not those of HM group, showed a significantly higher spontaneous locomotor
      activity in the open field, an impaired passive avoidance learning and
      significantly longer paw-lick latencies 24 h after footshock. Acquisition, but
      not retention, of the two-way active avoidance response was significantly
      impaired in all solvent-exposed groups. The XYL group did not differ
      significantly from PS, MES or HM group in any of the behavioral parameters. The
      above results show that a short-term exposure to any of the TMB isomers or m
      xylene at concentration as low as 100 ppm may induce persistent behavioral
      alterations in the rat.

PMID- 11307855
TI  - Nerve conduction and ATP concentrations in sciatic-tibial and medial plantar
      nerves of hens given phenyl saligenin phosphate.
AB  - To assess the relationship of nerve conduction and adenosine triphosphate (ATP)
      status in organophosphorus-induced delayed neuropathy (OPIDN), we evaluated both
      in adult hen peripheral nerves following exposure to a single 2.5 mg/kg dose of
      phenyl saligenin phosphate (PSP). ATP concentrations were determined at days 2,
      4, 7, and 14 post-dosing, from five segments (n = 5 per group) representing the
      entire length of the sciatic-tibial and medial plantar nerve. Initial effects of
      PSP dosing were seen in the most distal segment at day 2, when a transient ATP
      concentration increase (388 +/- 79 pmol/ml/mg versus control value of 215 +/- 23,
      P < 0.05) was noted. Subsequently, ATP concentration in this distal segment
      returned to normal. In the most proximal nerve segment, ATP concentrations were
      decreased on day 7, and further decreased on day 14 post-dosing (P < 0.05).
      Changes in ATP concentration and nerve conduction velocity begin at post-dosing
      day 2, and were found prior to development of clinical neuropathy and axonopathic
      lesions. These results suggest that alterations in sciatic-tibial and medial
      plantar nerve conduction associated with sciatic-tibial and medial plantar nerve
      ATP concentration are early events in the development of OPIDN.

PMID- 11307856
TI  - Regional potassium distribution in the brain in forensic relevant types of
      intoxication preliminary morphometric evaluation using a histochemical method.
AB  - A histochemical-morphometric method was used to measure potassium (K+) levels in
      gray and white matter of rats following sublethal intoxication with 11 different
      neurotoxic compounds of high forensic significance. Six rats were each given a
      single substance applied intraperitoneally, the same dosage being given to two
      animals each. The animals were subsequently killed, the brains immediately
      frozen, and cryosections cut. K+ levels were evaluated morphometrically. A drop
      in K+ levels was used as the criterion for cytotoxic edema. Application of
      ethanol, atropine, carbromal, carbon monoxide, morphine or triethyltin led to a
      rise in K+ levels in the gray matter and a simultaneous decline in the white
      matter. By contrast, administration of amitriptyline, glycerin, potassium
      cyanide, parathion or phenobarbital initiated an increase in K+ levels in both
      gray and white matter. A cytotoxic edema could thus be reliably excluded in these
      intoxications. Although the study design allows no statistical analysis, these
      conclusions are supported by the marked differences in K+ levels in gray and
      white matter induced by the different toxicants.

PMID- 11307857
TI  - A local training and pruning approach for neural networks.
AB  - The training of neural networks using the extended Kalman filter (EKF) algorithm
      is plagued by the drawback of high computational complexity and storage
      requirement that may become prohibitive even for networks of moderate size. In
      this paper, we present a local EKF training and pruning approach that can solve
      this problem. In particular, the by-products obtained along with the local EKF
      training can be utilized to measure the importance of the network weights.
      Comparing with the original global approach, the proposed local EKF training and
      pruning approach results in a much lower computational complexity and storage
      requirement. Hence, it is more practical in solving real world problems. The
      performance of the proposed algorithm is demonstrated on one medium- and one
      large-scale problems, namely, sunspot data prediction and handwritten digit
      recognition.

PMID- 11307858
TI  - Local linear independent component analysis based on clustering.
AB  - In standard Independent Component Analysis (ICA), a linear data model is used for
      a global description of the data. Even though linear ICA yields meaningful
      results in many cases, it can provide a crude approximation only for general
      nonlinear data distributions. In this paper a new structure is proposed, where
      local ICA models are used in connection with a suitable grouping algorithm
      clustering the data. The clustering part is responsible for an overall coarse
      nonlinear representation of the data, while linear ICA models of each cluster are
      used for describing local features of the data. The goal is to represent the data
      better than in linear ICA while avoiding computational difficulties related with
      nonlinear ICA. Several data grouping methods are considered, including standard K
      means clustering, self-organizing maps, and neural gas. Connections to existing
      methods are discussed, and experimental results are given for artificial data and
      natural images. Furthermore, a general theoretical framework encompassing a large
      number of methods for representing data is introduced. These range from global,
      dense representation methods to local, very sparse coding methods. The proposed
      local ICA methods lie between these two extremes.

PMID- 11307859
TI  - Combining regression trees and radial basis function networks.
AB  - We describe a method for non-parametric regression which combines regression
      trees with radial basis function networks. The method is similar to that of
      Kubat, who was first to suggest such a combination, but has some significant
      improvements. We demonstrate the features of the new method, compare its
      performance with other methods on DELVE data sets and apply it to a real world
      problem involving the classification of soybean plants from digital images.

PMID- 11307860
TI  - Dynamical properties of min-max networks.
AB  - In this paper we study the dynamical behavior of a class of neural networks where
      the local transition rules are max or min functions. We prove that sequential
      updates define dynamics which reach the equilibrium in O(n2) steps, where n is
      the size of the network. For synchronous updates the equilibrium is reached in
      O(n) steps. It is shown that the number of fixed points of the sequential update
      is at most n. Moreover, given a set of p < or = n vectors, we show how to build a
      network of size n such that all these vectors are fixed points.

PMID- 11307861
TI  - Neurocomputers: a dead end?
AB  - The last decade saw a proliferation of research into the design of
      neurocomputers. Although such work still continues, much of it is never beyond
      the prototype-machine stage. In this paper, we argue that, on the whole,
      neurocomputers are no longer viable; like, say, database computers before them,
      their time has passed before they became a common reality. We consider the
      implementation of hardware neural networks, from the level of arithmetic to
      complete individual processors and parallel processors and show that currents
      trends in computer architecture and implementation are not supportive of a case
      for custom neurocomputers. We argue that in the future, neural-network processing
      ought to be mostly restricted to general-purpose processors or to processors that
      have been designed for other widely-used applications. There are just one or two,
      rather narrow, exceptions to this.

PMID- 11307862
TI  - Rival Penalized Competitive Learning based approach for discrete-valued source
      separation.
AB  - This paper presents an approach based on Rival Penalized Competitive Learning
      (RPCL) rules for discrete-valued source separation. In this approach, we first
      build a connection between the source number and the cluster number of
      observations. Then, we use the RPCL rule to automatically find out the correct
      number of clusters such that the source number is determined. Moreover, we tune
      the de-mixing matrix based on the cluster centers instead of the observation
      themselves, whereby the noise interference is considerably reduced. The
      experiments have shown that this new approach not only quickly and automatically
      determines the number of sources, but also is insensitive to the noise in
      performing blind source separation.

PMID- 11307863
TI  - Obesity and coronary heart disease.
AB  - Obesity is commonly cited as a risk factor for the development of coronary heart
      disease (CHD). Epidemiologic studies tend to support this contention,
      particularly those focusing on patients with central obesity. Such studies
      however, are imprecise and prone to misclassification bias. Angiographic and post
      mortem studies have demonstrated little or no correlation of total fat mass and
      coronary atherosclerosis except in those with abdominal obesity. There is a
      strong association of obesity, particularly central obesity, and traditional risk
      factors for CHD such as hypertension, type II diabetes mellitus, and
      dyslipidemia. There may also be an association between obesity and several
      nontraditional risk factors such as hyperhomocystinemia, elevated Lp(a) levels
      and factors that increase thrombogenesis. Obesity may also alter endothelial
      function. Weight loss, although associated with favorable modification of
      multiple risk factors for CHD, has not been shown to independently and
      definitively reduce CHD risk.

PMID- 11307864
TI  - Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome.
AB  - Obesity produces an increase in total blood volume and cardiac output because of
      the high metabolic activity of excessive fat. In moderate to severe cases of
      obesity, this may lead to left ventricular dilation, increased left ventricular
      wall stress, compensatory (eccentric) left ventricular hypertrophy, and left
      ventricular diastolic dysfunction. Left ventricular systolic dysfunction may
      occur if wall stress remains high because of inadequate hypertrophy. Right
      ventricular structure and function may be similarly affected by the
      aforementioned morphologic and hemodynamic alterations and by pulmonary
      hypertension related to the sleep apnea/ obesity hypoventilation syndrome. The
      term obesity cardiomyopathy is applied when these cardiac structural and
      hemodynamic changes result in congestive heart failure. Obesity cardiomyopathy
      typically occurs in persons with severe and long-standing obesity. The
      predominant causes of death in those with obesity cardiomyopathy are progressive
      congestive heart failure and sudden cardiac death.

PMID- 11307865
TI  - Management of obesity cardiomyopathy.
AB  - Therapy of acute exacerbations of congestive heart failure associated with
      obesity cardiomyopathy consists of dietary salt restriction, inspired oxygen,
      diuretics, and angiotensin-converting enzyme inhibitors or, if left ventricular
      systolic dysfunction is present, hydralazine/isosorbide dinitrate. Digitalis may
      be indicated in selected cases. These measures may also be useful chronically in
      association with weight loss. Substantial weight loss is capable of reversing all
      of the hemodynamic abnormalities associated with obesity except elevation of left
      ventricular filling pressure. Substantial weight loss may also reduce left
      ventricular mass and improve left ventricular diastolic filling in those with
      left ventricular hypertrophy before weight loss. Left ventricular systolic
      function also improves after weight loss in those with impaired pre-weight-loss
      systolic function. These beneficial effects of weight loss occur partly because
      of favorable alterations in left ventricular loading conditions. Substantial
      weight loss in patients with congestive heart failure associated with obesity
      cardiomyopathy produces a reversal of many of the clinical manifestations of
      cardiac decompensation and improves New York Heart Association functional class
      in most patients.

PMID- 11307866
TI  - Obesity, hypertension, and the heart.
AB  - Hypertension occurs more commonly in obese than in lean persons at virtually
      every age. A variety of endocrine, genetic, and metabolic mechanisms have been
      linked to the development of obesity hypertension. These include insulin
      resistance and hyperinsulinemia, increased serum aldosterone levels, salt
      sensitivity and expanded plasma volume in the presence of increased peripheral
      vascular resistance, a genetic predisposition, and possibly increased leptin
      levels. Pressure and volume overload are present in obese hypertensives. This
      leads to a mixed eccentric-concentric form of left ventricular hypertrophy and
      increases the predisposition to congestive heart failure. Weight loss, even in
      modest decrements, is effective in reducing obesity-hypertension, possibly by
      ameliorating several of the proposed pathophysiologic mechanisms. There are
      currently no specific recommendations concerning pharmacotherapy of obesity
      hypertension because each drug group has pros and cons.

PMID- 11307867
TI  - Pulmonary complications of obesity.
AB  - Obesity can profoundly alter pulmonary function and diminish exercise capacity by
      its adverse effects on respiratory mechanics, resistance within the respiratory
      system, respiratory muscle function, lung volumes, work and energy cost of
      breathing, control of breathing, and gas exchange. Weight loss can reverse many
      of the alterations of pulmonary function produced by obesity. Obesity places the
      patient at risk of aspiration pneumonia, pulmonary thromboembolism, and
      respiratory failure. It is the most common precipitating factor for obstructive
      sleep apnea and is a requirement for the obesity hypoventilation syndrome, both
      of which are associated with substantial morbidity and increased mortality. There
      are numerous medical and surgical therapies for obstructive sleep apnea and
      obesity hypoventilation. Weight reduction in the obese is among the most
      effective of these measures.

PMID- 11307868
TI  - Cardiovascular complications of weight reduction diets.
AB  - Weight reduction diets may reduce the severity of risk factors for coronary heart
      disease such as diabetes mellitus, hypertension, and dyslipidemia. Several case
      reports and small studies of patients receiving starvation diets have reported
      hypotension and sudden cardiac death. Myofibrillar damage was documented in 1
      case. Very-low-calorie diets are generally safe and well-tolerated. However, low
      QRS voltage, QT interval prolongation, and both nonsustained ventricular
      arrhythmias and sudden cardiac death have been described in subjects treated with
      such diets. Orthostatic hypotension may complicate very-low-calorie protein diets
      because of sodium depletion and depressed sympathetic nervous system activity.
      Bariatric surgery is associated with disproportionately high mortality rates in
      both the perioperative and postoperative periods.

PMID- 11307869
TI  - Appetite suppressants and valvular heart disease.
AB  - The association between valvular heart disease and diet pills was discovered
      several years ago in a small cohort of patients. Subsequent uncontrolled surveys
      and reports suggested a prevalence of cardiac abnormalities as high as 30%. These
      results led to widespread concern by millions of appetite suppressant users and
      the withdrawal of both fenfluramine and dexfenfluramine from the market. Through
      this review of the literature, it becomes apparent that we have better defined
      the association between valvular heart disease and appetite suppressants;
      nonetheless, many questions and controversies remain. Most large scale,
      multicenter, controlled studies have shown that a prevalence of significant valve
      regurgitation is between 2 and 12% and that the likelihood of disease increases
      with increasing dose and/or duration of appetite suppressant use, but several
      other issues, such as the mechanism of action, remain unanswered.

PMID- 11307870
TI  - Anorectic drugs and pulmonary hypertension from the bedside to the bench.
AB  - Anorectic drugs have been used for more than 30 years as an aid in weight
      reduction for obese persons. The use of aminorex, an amphetamine analog that
      increases norepinephrine levels in the central nervous system, led to an epidemic
      of primary pulmonary hypertension (PPH) in Europe in the late 1960s and early
      1970s. The use of fenfluramine and later dexfenfluramine [drugs that inhibit 5
      hydroxytryptamine (5-HT) release and reuptake and increases 5-HT and thus 5-HT
      secretion in the brain] was associated with a second epidemic of PPH. All of
      these drugs have been voluntarily withdrawn from the market. The pathogenesis of
      PPH in patients treated with these agents is uncertain, but recent evidence
      suggests that potassium channel abnormalities and vasoactive and proliferative
      properties of 5-HT may play a role. There is increasing experimental evidence
      suggesting that aminorex, fenfluramine and dexfenfluramine inhibit 4
      aminopyridine-sensitive currents in potassium channels resulting in
      vasoconstriction in pulmonary resistance vessels and perhaps smooth muscle cell
      proliferation. 5-HT causes pulmonary artery vasoconstriction and smooth muscle
      cell proliferation. Its levels are known to be high in those with fenfluramine
      induced PPH. However, a firm cause-and-effect relationship has not yet been
      established. One potentially beneficial effect of the epidemics of anorectic
      related PPH is that it may have provided important insights into the causes of
      PPH unrelated to anorectic agents.

PMID- 11307871
TI  - Heterotaxy syndrome in an adult, with polysplenia, visceral and cardiovascular
      malposition.
AB  - A rare case of an asymptomatic heterotaxy syndrome associated with dextrocardia
      is presented in a 45-year-old woman. This anomaly was incidentally discovered on
      computed tomography and ultrasound of the upper abdomen. Besides the presence of
      multiple abnormally positioned spleens, right-sided stomach, left-sided liver,
      short pancreas and venous anomalies, like interrupted left-sided inferior vena
      cava with azygos continuation, and dextrocardia were seen. Although cardiac
      abnormalities are frequently associated with heterotaxy syndromes with
      polysplenia in children, this is far less frequent in adults because of early
      decease in children with cardiac abnormalities. To the best of our knowledge,
      this is the third reported case of heterotaxy with polysplenia associated with
      dextrocardia in an asymptomatic adult patient.

PMID- 11307872
TI  - MR imaging anatomy of the knee.
AB  - MRI of the knee joint is one of the most common and important clinical
      applications in most MRI units today. Thorough knowledge of the detailed anatomy
      is a prerequisite for the understanding of knee pathology. This article reviews
      the MR anatomy of menisci, the cruciate ligaments, the medial and lateral
      supporting structures, the extensor mechanism, synovial plicae around the joint
      and some pitfalls in the interpretation.

PMID- 11307873
TI  - Partial liquid ventilation with perfluorocarbon.

PMID- 11307874
TI  - Spinal ganglioneuroma presenting as a highly vascular lesion with hypertrophic
      venous drainage.
AB  - We present the case of a 33-year-old man with a highly vascular spinal
      ganglioneuroma associated with hypertrophic draining veins mimicking
      arteriovenous malformation. Ganglioneuromas are classically known as avascular
      and association with hypertrohic venous drainage has not been previously
      reported. The magnetic resonance imaging and digital subtraction angiography
      features of this benign tumor were strongly suspicious for malignancy because of
      the high vascularity caused by intratumoral arteriovenous shunts. This case
      emphasizes the importance of including ganglioneuroma in the differential
      diagnosis of vascular spinal tumors and recalls that hypertrophic draining veins
      may be associated with spinal tumors.

PMID- 11307875
TI  - Paravertebral and diaphragmatic mass: an ectopic location of bronchogenic cyst.
AB  - Bronchogenic cysts constitute one area of the broad spectrum of developmental
      anomalies of the primitive foregut. They arise from anomalous budding of the
      primitive tracheobronchial tube and are commonly located in the mediastinum or
      the lung parenchyma, closely related to the tracheobronchial tree. In rare cases,
      they can migrate to subpleural, pericardial, paravertebral and cervical
      locations, if embryological connections with their parent bronchus are lost.
      Plain chest radiography and computed tomography have been the primary imaging
      modalities used for diagnosis. Computed tomography is frequently associated with
      misleading information with respect to the cyst density. Magnetic resonance
      imaging has been shown to be useful in the differential diagnosis of cystic
      mediastinal masses. We present a patient with two asymptomatic bronchogenic cysts
      found at a distance from the tracheobronchial tree.

PMID- 11307876
TI  - "The boundary for growth of Zygosaccharomyces bailii in acidified products
      described by models for time to growth and probability of growth," a comment on:
      J. Food Prot. 63(2):222-230 (2000).

PMID- 11307877
TI  - Evaluation of volatile chemical treatments for lethality to Salmonella on alfalfa
      seeds and sprouts.
AB  - A study was done to evaluate natural volatile compounds for their ability to kill
      Salmonella on alfalfa seeds and sprouts. Acetic acid, allyl isothiocyanate (AIT),
      trans-anethole, carvacrol, cinnamic aldehyde, eugenol, linalool, methyl
      jasmonate, and thymol were examined for inhibitory and lethal activity against
      Salmonella by exposing inoculated alfalfa seeds to compounds (1,000 mg/liter of
      air) for 1, 3, and 7 h at 60 degrees C. Only acetic acid, cinnamic aldehyde, and
      thymol caused significant reductions in Salmonella populations (>3 log10 CFU/g)
      compared with the control (1.9 log10 CFU/g) after treatment for 7 h. Treatment of
      seeds at 50 degrees C for 12 h with acetic acid (100 and 300 mg/liter of air) and
      thymol or cinnamic aldehyde (600 mg/liter of air) significantly reduced
      Salmonella populations on seeds (>1.7 log10 CFU/g) without affecting germination
      percentage. Treatment of seeds at 50 degrees C with AIT (100 and 300 mg/liter of
      air) and cinnamic aldehyde or thymol (200 mg/liter of air) did not significantly
      reduce populations compared with the control. Seed germination percentage was
      largely unaffected by treatment with gaseous acetic acid, AIT, cinnamic aldehyde,
      or thymol for up to 12 h at 50 degrees C. The number of Salmonella on seeds
      treated at 70 degrees C for 80 min with acetic acid (100 and 300 mg/liter of
      air), AIT (100 mg/liter of air), and cinnamic aldehyde and thymol (600 mg/liter
      of air) at water activity (a(w)) 0.66 was not significantly different than the
      number inactivated on seeds at a(w) 0.49. Acetic acid at 200 and 500 mg/liter of
      air reduced an initial population of 7.50 log10 CFU/g of alfalfa sprouts by 2.33
      and 5.72 log10 CFU/g, respectively, within 4 days at 10 degrees C. whereas AIT at
      200 and 500 mg/liter of air reduced populations to undetectable levels; however,
      both treatments caused deterioration in sensory quality. Treatment of sprouts
      with 1 or 2 mg of AIT per liter of air adversely affected sensory quality but did
      not reduce Salmonella populations after 11 days of exposure at 10 degrees C.

PMID- 11307878
TI  - Hot water immersion to eliminate Escherichia coli O157:H7 on the surface of whole
      apples: thermal effects and efficacy.
AB  - The effect of hot water immersion on both the reduction of Escherichia coli
      O157:H7 on the apple surface and internal temperatures of the apple was assessed
      in this study. Microbial reductions were measured experimentally, whereas
      internal temperatures were calculated through a mathematical analysis of
      experimental heat transfer data obtained from the apples. A method was developed
      to provide a purely surface-based inoculation of E. coli O157:H7. Rinsing
      produced no reduction, and treatments at 80 and 95 degrees C produced reductions
      of more than 5 logs in 15 s or less. The heat transfer analysis based on
      experimental data was used to calculate surface heat transfer coefficients and
      predict temperatures throughout the apple. The analysis indicated a low heat
      transfer rate. Although it reduces thermal degradation, a low heat transfer rate
      precludes thermal-based reduction of any internalized microorganisms.

PMID- 11307879
TI  - Inhibition and reversal of Salmonella typhimurium attachment to poultry skin
      using zinc chloride.
AB  - A skin attachment model was used to determine if ZnCl2 would reverse or inhibit
      Salmonella attachment to broiler skin. In the reversal experiments, skin samples,
      treated first with 1 ml of Salmonella Typhimurium suspension (10(8) CFU/ml) for
      30 min, were then treated with 25 or 50 mM ZnCl2 for 5 or 15 min. Zinc chloride
      solutions were applied while the culture was present on the skin. In the
      inhibition experiments, ZnCl2 solutions were added first; treatment solutions
      were discarded after 5 or 15 min of application, and then the culture was added.
      Firmly and loosely attached Salmonella were enumerated on xylose lactose tergitol
      plates. A duplicate section of skin, subjected concurrently to the above
      treatments, was observed under a scanning electron microscope to enumerate
      attached bacteria directly. In the reversal experiments, 25 and 50 mM ZnCl2
      reduced (P < 0.01) firmly attached cells by 77 and 89%, respectively, when
      compared to the control (water). Micrographs indicated that 25 and 50 mM ZnCl2
      reduced (P < 0.1) Salmonella attachment by 69 and 99.9%, respectively, in the
      reversal experiments. In the inhibition experiments, 25 and 50 mM ZnCl2 reduced
      (P < 0.01) firmly attached cells by 82 and 91%, respectively. Reduction of
      Salmonella may be attributed, in part, to the bactericidal activity of ZnCl2 in
      addition to bacterial cell detachment.

PMID- 11307880
TI  - Predicting the behavior of Escherichia coli introduced as a postprocessing
      contaminant in shrikhand, a traditional sweetened lactic fermented milk product.
AB  - The increasing popularity of traditional milk-based foods has placed emphasis on
      the need for microbial safety in food-chain establishments, as there are ample
      possibilities for foodborne pathogens to occur as postprocessing contaminants.
      The behavioral pattern of an enterotoxigenic strain of Escherichia coli D 21
      introduced as a postprocessing contaminant in shrikhand, a traditional sweetened
      lactic fermented milk product, was studied with variables of initial inoculum
      (4.3, 5.3, and 6.3 log10 CFU/g), storage temperature (4, 10, and 16 degrees C),
      and storage period (4, 9, and 14 days). During storage of shrikhand prepared
      individually with Lactobacillus delbruecki ssp. bulgaricus CFR 2028 and
      Lactococcus lactis ssp. cremoris B-634, there was a steady decrease in the viable
      count of E. coli that was proportional to the initial inoculum of E. coli
      introduced into shrikhand. The data were subjected to multivariate analysis, and
      equations were derived to predict the behavior of E. coli in shrikhand. The
      predicted values for the probable survival of E. coli showed good agreement with
      the experimental values with a majority of these predictions being fail-safe. The
      values of statistical indices showed that the model fits ranged between extremely
      good and satisfactory. Response surface plots were generated to describe the
      behavioral pattern of E. coli. The derived models and response surface plots
      enabled prediction of the survival of E. coli in shrikhand as a function of
      initial inoculum levels, storage temperatures, and storage periods of shrikhand.
      These predictions were valid within the limits of the experimental variables used
      to develop the model.

PMID- 11307881
TI  - Antimicrobial edible packaging based on cellulosic ethers, fatty acids, and nisin
      incorporation to inhibit Listeria innocua and Staphylococcus aureus.
AB  - Edible cellulosic films made with hydroxypropylmethylcellulose (HPMC) have proven
      to be inadequate moisture barriers. To improve its water vapor barrier
      properties, different hydrophobic compounds were incorporated into the HPMC
      matrix. Some fatty acids and derivatives were included into the film-forming
      solution prior to film formation. Stearic acid was chosen because of its high
      capacity to reduce significantly the water vapor transmission rate. Antimicrobial
      activity of edible HPMC film was obtained by the incorporation of nisin into the
      film-forming solution. Nisin is an antimicrobial peptide effective against gram
      positive bacteria. The inhibitory activity of this bacteriocin was tested for
      inhibition of Listeria innocua and Staphylococcus aureus. The use of stearic acid
      was observed to reduce the inhibitory activity of active HPMC film against both
      selected strains. This phenomenon may be explained by electrostatic interactions
      between the cationic nisin and the anionic stearic acid. Further studies showed
      that antimicrobial activity of film varied with the nature of the hydrophobic
      compound incorporated, in decreasing order: film without lipid, methylstearate
      film, and stearic acid film. This corroborated the idea of electrostatic
      interactions.

PMID- 11307882
TI  - Effect of benzalkonium chloride on viability and energy metabolism in exponential
      and stationary-growth-phase cells of Listeria monocytogenes.
AB  - The difference in killing exponential- and stationary-phase cells of Listeria
      monocytogenes by benzalkonium chloride (BAC) was investigated by plate counting
      and linked to relevant bioenergetic parameters. At a low concentration of BAC (8
      mg liter(-1)), a similar reduction in viable cell numbers was observed for
      stationary-phase cells and exponential-phase cells (an approximately 0.22-log
      unit reduction), although their membrane potential and pH gradient were
      dissipated. However, at higher concentrations of BAC, exponential-phase cells
      were more susceptible than stationary-phase cells. At 25 mg liter(-1), the
      difference in survival on plates was more than 3 log units. For both types of
      cells, killing, i.e., more than 1-log unit reduction in survival on plates,
      coincided with complete inhibition of acidification and respiration and total
      depletion of ATP pools. Killing efficiency was not influenced by the presence of
      glucose, brain heart infusion medium, or oxygen. Our results suggest that growth
      phase is one of the major factors that determine the susceptibility of L.
      monocytogenes to BAC.

PMID- 11307883
TI  - Thermal inactivation of stationary-phase and salt-adapted Listeria monocytogenes
      during postprocess pasteurization of surimi-based imitation crab meat.
AB  - The heat resistance of Listeria monocytogenes in surimi-based imitation crab meat
      was examined after growth to stationary phase or adaptation to 15% NaCl. An in
      package pasteurization treatment at the cold spot of 71.1 degrees C for 15 s was
      calculated as adequate to inactivate 5 logs of L. monocytogenes (z-value of 5.8
      degrees C). The heat resistance of L. monocytogenes in surimi did not increase
      after adaptation to salt.

PMID- 11307884
TI  - Altering the thermal resistance of foodborne bacterial pathogens with an eggshell
      membrane waste by-product.
AB  - Eggshells from egg-breaking operations are a significant waste disposal problem.
      Thus, the development of value-added by-products from this waste would be
      welcomed by the industry. The ability of extracted eggshell membranes containing,
      several bacteriolytic enzymes (i.e., lysozyme and beta-N-acetylglucosaminidase)
      or other membrane components to alter the thermal resistance of gram-positive and
      gram-negative bacterial pathogens was evaluated. Mid-log phase cells of
      Salmonella Enteritidis (SE), Salmonella Typhimurium (ST), Escherichia coli
      O157:H7 (EC), Listeria monocytogenes Scott A (LM), and Staphylococcus aureus (SA)
      were suspended in 100 ml of 0.1% peptone water (pH 6.9, 10(7-8) CFU/ml)
      containing either 0 (control) or 10 g of an eggshell membrane extract and
      incubated at 37 degrees C for 45 min. Following exposure, membrane-free samples
      (1.5 ml) were heated in a 56 degrees C (LM, SA), 54 degrees C (SE, ST), or 52
      degrees C (EC) water bath from 0 to 14 min in sealed glass reaction vials (12 by
      32 mm), and the survivors were recovered on brain heart infusion agar. Population
      reductions ranging from 27.6% (SA) to 99.8% (LM) (ST, 43.8%; SE, 47.5%; EC,
      71.8%) were observed for cells treated for 45 min with extracted membrane, as
      compared to controls. D-value reductions ranging from 0 (LM) to 87.2% (SE) (SA,
      36.7%; EC, 83.3%; ST, 86.3%) were observed when membrane-treated cells were
      subsequently heat inactivated. The effects of exposure pH, time, temperature, and
      organic load on membrane activity were also evaluated with Salmonella
      Typhimurium. Exposure pH (5.0 versus 6.9), time (15 versus 45 min), and
      temperature (4 degrees C versus 37 degrees C) did not significantly reduce the
      impact of eggshell membranes on D-values. However, the presence of organic matter
      (0.1% peptone water versus skim milk) significantly reduced the thermal
      resistance-reducing capacity of the membranes. These preliminary findings provide
      information on the potential use of extracted eggshell membranes to alter
      bacterial heat resistance.

PMID- 11307885
TI  - Attachment of bacteria to beef from steam-pasteurized carcasses.
AB  - The extent to which a bacterial cocktail containing equal numbers of Pseudomonas
      fragi NCTC 10689, Listeria monocytogenes BL5/2, Salmonella Typhimurium LT2, and
      Escherichia coli JM 109 attached to loin surface cuts (7 by 5 cm) derived from
      steam-pasteurized beef carcasses has been evaluated. The extent of attachment was
      categorized as loosely attached (removed by rinsing), firmly attached (released
      by stomaching), and irreversibly bound. No significant difference (P > 0.10) in
      the attachment of bacteria to steam-pasteurized carcasses was found compared with
      control loin samples that had received no treatment. No significant difference (P
      > 0.05) was also found in the attachment strength between the different bacterial
      species tested. Most bacteria inoculated onto the loin cuts were reversibly
      bound, since they had been removed by rinsing and stomaching. The irreversible
      attachment of bacteria to loin cuts was found to vary significantly (P < 0.01)
      among the different carcass sets used but was independent of whether the carcass
      had undergone steam pasteurization treatment. Use of a bioluminescent strain of
      E. coli showed that cells bound preferentially to cut edges and convoluted areas
      on the loin surface and could not be removed by rinsing. The possible mechanisms
      of bacterial attachment and the suitability of steam pasteurization to remove
      contamination incurred during slaughter are discussed.

PMID- 11307886
TI  - Microbiological quality of chilled beef carcasses in Northern Ireland: a baseline
      survey.
AB  - To standardize the assessment of the hygienic quality of beef carcasses in
      Northern Ireland (NI) abattoirs, swabbing techniques were evaluated. Six
      materials, including two commercially produced swabs, were compared for their
      ability to recover spoilage and pathogenic bacteria and for their ease of use as
      carcass swabs. A sponge retailed for domestic use was selected on the basis of
      efficiency of recovery of microorganisms, ease of use, and cost. On sample
      carcasses, 1,000 cm2 of the brisket was swabbed, since this site is normally
      readily contaminated. For 9 months, 420 carcasses in seven of the nine European
      Union-approved abattoirs in NI were sampled while in the chiller (24 to 48 h
      after kill). Total viable count (TVC), yeasts and molds, and Enterobacteriaceae
      were enumerated after incubation at 22 (48 h) and 37 degrees C (48 h), and the
      results were expressed as log CFU/cm2. The mean TVC results at 22 and 37 degrees
      C were 2.80+/-0.70 and 2.75+/-0.64, respectively. Although 63% of samples had
      yeasts that grew at 22 degrees C, only 35% were positive at 37 degrees C. The
      respective mean yeast counts were 1.12+/-0.59 and 0.46+/-0.51. Enterobacteriaceae
      were present in 15% of samples at 22 degrees C and 21% of samples at 37 degrees
      C. The mean counts for positive samples were 0.41+/-0.37 and 0.40+/-0.30,
      respectively. Molds were found in less than 4% of samples. Given that the brisket
      is normally one of the most heavily contaminated parts of the carcass, these
      results suggest that good hygienic practices are in operation in NI abattoirs.
      The results also enabled the abattoirs with the cleanest carcasses to be
      identified, hence permitting best practices to be found.

PMID- 11307887
TI  - Microbial contamination occurring on lamb carcasses processed in the United
      States.
AB  - Lamb carcasses (n = 5,042) were sampled from six major lamb packing facilities in
      the United States over 3 days during each of two visits (fall or winter, October
      through February; spring, March through June) in order to develop a
      microbiological baseline for the incidence (presence or absence) of Salmonella
      spp. and for populations of Escherichia coli after 24 h of chilling following
      slaughter. Samples also were analyzed for aerobic plate counts (APC) and total
      coliform counts (TCC). Additionally, incidence (presence or absence) of
      Campylobacter jejuni/coli on lamb carcasses (n = 2,226) was, determined during
      the slaughtering process and in the cooler. All samples were obtained by sponge
      sampling the muscle-adipose tissue surface of the flank, breast, and leg of lamb
      carcasses (100 cm2 per site; 300 cm2 total). Incidence of Salmonella spp. in
      samples collected from chilled carcasses was 1.5% for both seasons combined, with
      1.9% and 1.2% of fall or winter and spring samples being positive, respectively.
      Mean (log CFU/cm2) APC, TCC, and E. coli counts (ECC) on chilled lamb carcasses
      across both seasons were 4.42, 1.18, and 0.70, respectively. APC were lower (P <
      0.05) in samples collected in the spring versus fall or winter, while TCC were
      higher in samples collected in the spring. There was no difference (P > 0.05)
      between ECC from samples collected in the spring versus winter. Only 7 out of
      2,226 total samples (0.3%) tested positive for C. jejuni/coli, across all
      sampling sites. These results should be useful to the lamb industry and
      regulatory authorities as new regulatory requirements for meat inspection become
      effective.

PMID- 11307888
TI  - Comparisons of microbiological evaluations of selected kitchen areas with visual
      inspections for preventing potential risk of foodborne outbreaks in food service
      operations.
AB  - Most local health departments utilize visual, but not microbiological, methods
      when inspecting food service operations. To evaluate the marginal utility of
      microbial testing for minimizing potential risks of foodborne outbreaks in
      restaurants, swab samples were taken from handwashing sink faucets, freshly
      cleaned and sanitized food-contact surfaces, and from cooler or freezer door
      handles in 70 of 350 category-three (high-risk) food service operations in
      Toledo, Ohio. The swabs were inoculated onto different selective media, and
      standard procedures were used to identify pathogenic and nonpathogenic bacteria.
      Microbiological evaluations of the sampled food service operations were compared
      with visual inspection reports, using a numeric rating scale. Enteric bacteria
      (that may indicate fecal contamination) were found on food contact surfaces, on
      cooler or freezer door handles, and on handwashing sink faucets in 86, 57, and
      53% of the food service operations, respectively. Approximately 27, 40, and 33%
      of the restaurants received visual ratings of very poor to poor, fair, and good
      to very good, respectively. In comparison, 10, 17, and 73% of the restaurants
      received microbiological rating scores of very poor to poor, fair, and good to
      very good, respectively. Restaurants with trained personnel received
      significantly higher visual rating scores than restaurants without trained
      personnel (P < 0.01). Although more restaurants received poor rating scores by
      visual inspection than by microbiological evaluation, the presence of fecal
      bacteria from different sites in more than 50% of the food service operations
      indicated that visual inspection alone might not be sufficient for minimizing
      potential risk for foodborne disease outbreaks. Therefore, we recommend periodic
      microbiological evaluation of high-risk food service operations, in addition to
      visual inspection, for minimizing the risk of foodborne disease outbreaks.

PMID- 11307889
TI  - The effect of growth stage and growth temperature on high hydrostatic pressure
      inactivation of some psychrotrophic bacteria in milk.
AB  - The effect of high hydrostatic pressure on the survival of the psychrotrophic
      organisms Listeria monocytogenes, Bacillus cereus, and Pseudomonas fluorescens
      was investigated in ultrahigh-temperature milk. Variation in pressure resistance
      between two strains of each organism were studied. The effect of growth stage
      (exponential and stationary phase), growth temperature (8 and 30 degrees C) on
      pressure resistance, and sublethal pressure injury were investigated. Exponential
      phase cells were significantly less resistant to pressure than stationary-phase
      cells for all of the three species studied (P < 0.05). Growth temperature was
      found to have a significant effect at the two growth stages studied. Exponential
      cells grown at 8 degrees C were more resistant than those grown at 30 degrees C,
      but for stationary-phase cells the reverse was true. B. cereus stationary-phase
      cells grown at 30 degrees C were the most pressure resistant studied. L.
      monocytogenes showed the most sublethal damage compared to B. cereus and P.
      fluorescens. B. cereus spores were more resistant to pressure than vegetative
      cells. Pressure treatment at 400 MPa for 25 min at 30 degrees C gave a 0.45-log
      inactivation. Pressure treatment at 8 degrees C induced significantly less spore
      germination than at 30 degrees C. This study indicates the importance of the
      history of a bacterial culture prior to pressure treatment and that bacterial
      spores require more severe pressure treatments, probably in combination with
      other preservation techniques, to ensure inactivation.

PMID- 11307890
TI  - Inactivation of Cryptosporidium parvum oocysts in cider by flash pasteurization.
AB  - Cryptosporidium parvum is a well-recognized pathogen of significant medical
      importance, and cider (apple juice) has been associated with foodborne
      cryptosporidiosis. This study investigated the effect of flash pasteurization on
      the viability of contaminant C. parvum oocysts. Cider inoculated with oocysts was
      heated at 70 or 71.7 degrees C for 5, 10, or 20 s, and oocyst viability was
      measured by a semiquantitative in vitro infectivity assay. By infecting multiple
      wells of confluent Madin-Darby bovine kidney cells with serial dilutions of heat
      treated oocysts and examining infected cells by indirect fluorescent antibody
      staining, the most probable number technique was applied to quantify log
      reduction of oocyst viability. Heating for 10 or 20 s at either temperature
      caused oocyst killing of at least 4.9 log (or 99.999%), whereas oocyst
      inactivation after pasteurization for 5 s at 70 and 71.7 degrees C was 3.0 log
      (99.9%) and 4.8 log (99.998%), respectively. Our results suggested that current
      practices of flash pasteurization in the juice industry are sufficient in
      inactivating contaminant oocysts.

PMID- 11307891
TI  - Production of alternariol and alternariol methyl ether by Alternaria alternata
      grown on fruits at various temperatures.
AB  - Two toxigenic strains of the fungus Alternaria alternata (ATCC 56836 and ATCC
      66868) were grown on surface-disinfected, fresh, ripe fruits and tested for the
      production of alternariol (AOH) and alternariol methyl ether (AME). Examined
      fruits included strawberries; red and green seedless grapes; concord grapes; red
      delicious, golden delicious, and gala apples; and blueberries. After inoculation,
      fruits were incubated at 4, 10 degrees C, or room temperature (approximately 21
      degrees C) for up to 3 weeks. At weekly intervals, duplicate samples were
      analyzed for AOH and AME by using liquid chromatography. Results indicated that
      A. alternata and its metabolites were not a major problem in strawberries due to
      the presence of fast-growing molds like Rhizopus and Botrytis that outgrew and
      possibly inhibited Alternaria. Both Alternaria strains showed limited growth on
      apples, although fast-growing molds were not present after surface disinfection;
      AOH and AME were produced only by the ATCC 56836 strain on the golden delicious
      and gala varieties, (ranging from <0.1 to 5 microg/g and <0.1 to 14 microg/g for
      AOH and AME, respectively). Restricted growth of both strains without toxin
      production occurred in blueberries, whereas moderate growth and AOH (<0.1 to
      3,336 microg/g) and AME (<0.1 to 1,716 microg/g) production took place in grapes.

PMID- 11307892
TI  - Determination of ochratoxin A in red wine and vinegar by immunoaffinity high
      pressure liquid chromatography.
AB  - A method is described for the determination of ochratoxin A (OTA) in red wine and
      vinegar using an acidic chloroform extraction, an immmunoaffinity clean-up step,
      and a high-performance liquid chromatographic determination with fluorescence
      detection. The detection limit was estimated at 0.002 microg/liter. The mean
      recovery factors were found at 91.3 and 96.6% for wine and vinegar, respectively.
      Thirty-one samples of red wine originating from Mediterranean sea countries and
      15 samples of vinegar were examined for the presence of OTA. All red wine samples
      contained OTA. Seventy-two percent of these samples were found to be contaminated
      over 0.1 microg/liter. Among them, nine samples contained ochratoxin A in the
      range of 0.5 to 3.4 microg/liter, 12 samples in the range of 0.10 to 0.50
      microg/liter (median: 0.176 microg/liter), and 9 samples in the range of 0.010 to
      0.100 microg/liter (median: 0.041 microg/liter). All 15 vinegar samples showed
      the presence of OTA. The most contaminated ones were three balsamic vinegar
      samples containing 0.156 microg/liter, 0.102 microg/liter, and 0.252 microg/liter
      of OTA. In the remaining 12 samples, ochratoxin A levels ranged from 0.008
      microg/liter to 0.046 microg/liter (median: 0.012 microg/liter). These data are
      in good agreement with the hypothesis that wine originating from Southern
      countries might contain significant OTA concentration and showed the possible
      occurrence of traces of OTA in vinegar.

PMID- 11307893
TI  - Quantification of the contamination of chicken and chicken products in the
      netherlands with Salmonella and Campylobacter.
AB  - The research described in this contribution provides quantitative data on
      contamination levels with Salmonella and Campylobacter in chicken and chicken
      products in The Netherlands at retail level using the most probable number method
      and direct counting. Most samples contained <10 Salmonella per carcass, both in
      fresh (89%) and frozen (68%) products, contamination levels with Campylobacter
      varied from <10 (18%) to more than 5,500 (18%) per fresh carcass. Most frozen
      samples (57%) contained < 10 Campylobacter per carcass.

PMID- 11307894
TI  - Incidence of Salmonella in five Swedish slaughterhouses.
AB  - Five Swedish slaughterhouses where pig slaughter takes place were sampled and
      tested for Salmonella. Each slaughterhouse was visited six times, and sampling
      was done repeatedly at specific points in the slaughter line during the day. Both
      sampling of pork carcasses and the slaughterhouse environment was done. This
      study was part of a larger European project, entitled Salmonella in Pork
      (Salinpork), with the aim of identifying specific risk points or risk factors
      associated with Salmonella contamination that contribute to health hazards for
      humans. During the study, a total of 3,388 samples from the five slaughterhouses
      were collected and cultured for Salmonella. All of the samples were culture
      negative for Salmonella.

PMID- 11307895
TI  - Survival of staphylococcus aureus and Escherichia coli as affected by ethanol and
      NaCl.
AB  - Growth of three strains of Staphylococcus aureus and two strains of Escherichia
      coli on nutrient agar (NA) supplemented with ethanol and NaCl was investigated.
      S. aureus did not grow on NA containing > or =10% ethanol (wt/wt) combined with >
      or =0% NaCl (wt/wt), or 7.5% ethanol combined with 7.5% NaCl. Neither E. coli nor
      E. coli O157:H7 grew on NA containing > or =7.5% ethanol combined with > or =0%
      NaCl, 5% ethanol combined with > or =2.5% NaCl, or > or =5% NaCl combined with >
      or =0% ethanol. It is apparent that NaCl enhanced the inhibitory effect of
      ethanol on growth of S. aureus and E. coli When cells were suspended in nutrient
      broth containing 12.5, 20, or 40% ethanol combined with NaCl, viable cells
      decreased with an increase of ethanol concentration. Ethanol sensitivity among
      strains and between genera varied in a limited range. When the cells were exposed
      to 20% ethanol in combination with 5% NaCl, S. aureus and E. coli lost viability
      after 30 and 10 min, respectively. When treated with 40% ethanol combined with >
      or =0% NaCl, all test strains lost viability within 5 min.

PMID- 11307896
TI  - Listeria species in raw and ready-to-eat foods from restaurants.
AB  - From September 1999 to March 2000, meat (pork, beef, and chicken), fish (salmon,
      hake, and sole), vegetable (lettuce and spinach), and Spanish potato omelette
      samples obtained at restaurants were collected and tested for the occurrence of
      Listeria spp. Listeria monocytogenes was isolated from 3 (2.9%) out of 103
      studied samples. Other species isolated were Listeria grayi (13.6%), Listeria
      innocua (1.9%), Listeria ivanovii (5.8%), Listeria seeligeri (3.9%), and Listeria
      welshimeri (1.9%). Listeria was neither isolated from beef nor any type of fish.

PMID- 11307897
TI  - Incidence and characterization of Listeria spp. from foods available in Korea.
AB  - A total of 410 domestic Korean food samples were analyzed for the presence of
      Listeria spp. by the conventional U.S. Department of Agriculture protocol, and
      presumptive strains were identified by morphological, cultural and biochemical
      tests according to Bergey's manual and confirmed by API-Listeria kit. Among the
      total 410 food samples, 46 samples (11.2%) were found to be contaminated with
      Listeria species. Among the 46 strains of Listeria spp. isolates, 8 strains
      (17.42%) for Listeria monocytogenes, 3 strains (6.5%) for Listeria seeligeri, 33
      strains (71.7%) for Listeria innocua, and 2 strains (4.4%) for Listeria
      welshimeri were identified, respectively. Also, only beef, chicken, pork, frozen
      foods, and sausage were contaminated with L. monocytogenes, and the other
      products were free of L. monocytogenes. Of 46 Listeria spp. isolates, L. innocua
      (71.7%) was the most predominantly isolated in a variety of foods compared to
      other Listeria spp. An in vitro virulence assay for Listeria spp. using myeloma
      and hybridoma cells from murine and human sources was performed. The result
      showed that only L. monocytogenes killed approximately 95 to 100% hybridoma cells
      after 6 h and the other Listeria species, such as L. innocua, L. seeligeri, and
      L. welshimeri strains had about 0 to 10% lethal effect on hybridoma cells. Also,
      an antibiotic susceptibility test showed that Listeria spp. isolates were very
      susceptible to the antibiotics tested, except for nalidixic acid. Also,
      serotyping results showed 75% of L. monocytogenes isolates from beef, chicken,
      and frozen pizza belonged to serotype 1 and 25% from sausage were type 4.

PMID- 11307898
TI  - Characterization of the lactic acid bacteria in ewe's milk and cheese from
      northwest Argentina.
AB  - Indigenous lactic acid bacteria in ewe's milk and artisanal cheese were studied
      in four samples of fresh raw milk and four 1-month-old cheeses from the provinces
      of northwest Argentina. Mean growth counts on M17, MRS, and MSE agar media did
      not show significant differences (P < 0.05) in raw milk and cheeses. Isolates of
      lactic acid bacteria from milk were identified as Enterococcus (48%), lactococci
      (14%), leuconostocs (8%), and lactobacilli (30%). All lactococci were identified
      as Lactococcus lactis (subsp. lactis and subsp. cremoris). Lactobacilli were
      identified as Lactobacillus plantarum (92%) and Lactobacillus acidophilus (8%).
      Enterococci (59%) and lactobacilli (41%) were isolated from cheeses. L. plantarum
      (93%), L. acidophilus (5%), and Lactobacillus casei (2%) were most frequently
      isolated. L. lactis subsp. lactis biovar diacetylactis strains were considered as
      fast acid producers. L. lactis subsp. cremoris strains were slow acid producers.
      L. plantarum and L. casei strains identified from the cheeses showed slow acid
      production. The majority of the lactobacilli and Lactococcus lactis strains
      utilized citrate and produced diacetyl and acetoin in milk. Enzyme activities
      (API-ZYM tests) of lactococci were low, but activities of L. plantarum strains
      were considerably higher. The predominance of L. plantarum in artisanal cheese is
      probably important in the ripening of these cheeses due to their physiological
      and biochemical characteristics.

PMID- 11307899
TI  - Validation of a polymerase chain reaction method for the detection of rendered
      bovine-derived materials in feedstuffs.
AB  - This study validated a polymerase chain reaction-based method for the detection
      of a specific bovine mitochondrial gene derived from rendered bovine tissues and
      admixed with complete animal feed. Four laboratories participated in this effort:
      one state laboratory and three Food and Drug Administration (FDA) laboratories,
      including one FDA field laboratory. The protocol used a statistical approach of
      90% probability, with a 95% confidence interval for determining acceptable rates
      of false-positive and false-negative samples. Each participating laboratory
      analyzed 30 samples of feed each containing 0, 0.125, and 2.0% bovine meat and
      bone meal (BMBM), for a total of 90 feed samples. The samples were randomized
      such that the analysts were unaware of the true identity of the test samples. The
      results demonstrated that all laboratories met the acceptance criteria
      established for this protocol. The overall rates of false-negative results were
      0.83% (1/120) at the level of 0.125% BMBM and 1.67% (2/120) at the level of 2%
      BMBM. The overall rate of false-negative results for all levels of BMBM was 1.25%
      (3/240). The rate for false-positive results was 0.83%.

PMID- 11307900
TI  - Production of alternaria mycotoxins by Alternaria alternata isolated from weather
      damaged wheat.
AB  - The production of Alternaria mycotoxins by Alternaria alternata isolated from
      Chinese weathered wheat kernels were first investigated on polished rice and
      durum wheat grains. These mycotoxins included alternariol (AOH) and its
      monomethyl ether (AME), altenuene (ALT), altertoxin I (ATX-I), and tenuazonic
      acid (TA). Of 25 isolates tested, all were AOH and AME producers, 21 (84%)
      coproduced ALT and ATX-I, and 8 (32%) produced TA in rice culture. TA was the
      most abundant toxin produced at a level ranging from 1,369 to 3,563 mg/kg. Much
      smaller amounts of AOH, AME, ALT, and ATX-I were present with average
      concentrations of 54, 40, 44, and 8 mg/kg, respectively. There were linear
      correlations between the level of AOH and AME (r = 0.846), alternariols (AOH plus
      AME) and ALT (r = 0.785), and ATX-I and TA (r = 0.553). Polished rice medium
      seems to support a bit more production of Alternaria metabolites than wheat but
      with an insignificant difference in concentrations (P > 0.05). A study of the
      time-course of toxin production by A. alternata isolates indicated that AOH
      production began faster than any other toxins monitored, and ALT production
      exhibited a progressive increase throughout the experiment. TA producers might
      reveal their considerably higher ability to produce toxin in the field despite
      their low frequency.

PMID- 11307901
TI  - A review of hepatitis E virus.
AB  - Hepatitis E virus (HEV) is a major cause of outbreaks and sporadic cases of viral
      hepatitis in tropical and subtropical countries but is infrequent in
      industrialized countries. The virus is transmitted by the fecal-oral route with
      fecally contaminated drinking water being the usual vehicle. Hepatitis resulting
      from HEV infection is a moderately severe jaundice that is self-limiting in most
      patients. Young adults, 15 to 30 years of age, are the main targets of infection,
      and the overall death rate is 0.5 to 3.0%. However, the death rate during
      pregnancy approaches 15 to 25%. Death of the mother and fetus, abortion,
      premature delivery, or death of a live-born baby soon after birth are common
      complications of hepatitis E infection during pregnancy. Hepatitis E virus is
      found in both wild and domestic animals; thus, HEV is a zoonotic virus. The
      viruses isolated from swine in the United States or Taiwan are closely related to
      human HEV found in those areas. The close genetic relationship of the swine and
      human virus suggests that swine may be a reservoir of HEV. In areas where swine
      are raised, swine manure could be a source of HEV contamination of irrigation
      water or coastal waters with concomitant contamination of produce or shellfish.
      Increasing globalization of food markets by industrialized countries has the
      potential of introducing HEV into new areas of the world. The purpose of this
      review is to cover certain aspects of hepatitis E including the causative agent,
      the disease, diagnosis, viral detection, viral transmission, epidemiology,
      populations targeted by HEV, and the role of animals as potential vectors of the
      virus.

PMID- 11307902
TI  - Stroboscopic assessment of vocal fold keratosis and glottic cancer.
AB  - Disruption of the normal viscoelastic properties of the superficial lamina
      propria (SLP) results in aberrant vocal fold vibration and mucosal wave
      propagation. Therefore, an investigation was performed to determine whether
      stroboscopy is a reliable method for 1) differentiating invasive glottic
      carcinoma from intraepithelial atypia or 2) determining the depth of cancer
      invasion. An analysis was done on the preoperative vocal fold vibration
      characteristics of 62 keratotic (intraepithelial, 45; cancer, 17) lesions that
      were subsequently resected by means of microlaryngoscopy. Histopathology and
      intraoperative mapping were used to specify the depth of invasion. A panel of 4
      blinded judges was used to assess the amplitude of vocal fold vibration and the
      magnitude of mucosal wave activity in the region of the lesion from
      videostroboscopic recordings. The final comparative data set comprised only those
      ratings that achieved at least 75% interjudge agreement. Of the 28
      intraepithelial lesions that could be reliably evaluated for amplitude of vocal
      fold vibration, only 2 were normal, with the amplitude reduced in 24 and absent
      in 2. Of the 30 intraepithelial lesions in which mucosal wave activity could be
      reliably assessed, only 2 were normal, with the wave reduced in 24 and absent in
      4. Furthermore, amplitude of vocal fold vibration and magnitude of mucosal wave
      propagation were absent in 2 of 4 carcinomas in which the depth of microinvasion
      did not reach the vocal ligament. According to the findings herein, reduced
      amplitude of vocal fold vibration and/or mucosal wave propagation associated with
      keratosis did not reliably predict the presence of cancer or the depth of cancer
      invasion into the laminae propriae. However, the presence of a flexible mucosal
      wave probably indicates that there is not extensive vocal ligament invasion.
      Reductions in the amplitude of vocal fold vibration and in mucosal wave magnitude
      were usually noted in intraepithelial atypia, despite the fact that there was no
      invasion into the SLP. The reduced epithelial pliability could be due to bulky
      keratosis and/or alteration of the SLP occurring as a result of inflammation or
      fibrovascular scarring.

PMID- 11307903
TI  - Role of laryngoscopy, dual pH probe monitoring, and laryngeal mucosal biopsy in
      the diagnosis of pharyngoesophageal reflux.
AB  - There is no standard for determining significant pharyngoesophageal reflux. This
      prospective blind comparison study compared dual pH probe studies, direct
      laryngoscopy, and mucosal biopsy in children without symptoms of gastroesophageal
      reflux who underwent airway evaluation. Significant reflux to the lower
      esophageal probe did not correlate with statistical significance with reflux to
      the upper probe. In this group of asymptomatic patients, a positive lower pH
      probe finding did not correlate with upper or lower esophageal mucosal
      inflammation. Eosinophilia in the esophageal mucosa is diagnostic of
      gastroesophageal reflux disease, and was seen in 5 of the laryngeal biopsies. A
      weak correlation was seen between positive findings at laryngoscopy and positive
      posterior cricoid biopsy in this group. There may be no consistent way to predict
      significant pharyngoesophageal reflux in asymptomatic patients. Single-probe pH
      testing will not predict significant pharyngoesophageal reflux with mucosal
      changes. Laryngoscopy and upper pH probe findings only weakly correlate with
      significant histologic findings. Laryngeal and posterior cricoid biopsy may be
      the only sensitive test for mucosal injury. Clinical trials of empiric antireflux
      therapy should be used to determine whether the laryngeal changes seen in these
      patients are reversible.

PMID- 11307904
TI  - Idiopathic progressive subglottic stenosis: findings and treatment in 52
      patients.
AB  - Rarely, patients develop severe idiopathic subglottic stenosis. In 34 years, we
      have observed this disorder in 52 patients. All but 1 of the patients were female
      -a finding that suggests a hormonal cause. Without treatment, the airway
      progressively narrows--in some cases, until the patient requires tracheotomy.
      Laser submucosal resection and rotation mucosal flaps open and stabilize the
      airway and provide effective palliation. However, unlike traumatic subglottic
      stenosis, which has been cured with this technique, the idiopathic form causes
      submucosal fibrosis that regenerates spontaneously. Thus, treatment helps, but
      does not cure, the patient. The characteristic pathological finding is of
      submucosal dense fibrotic tissue with evidence of chronic inflammation. The
      clinical findings and treatment are here discussed.

PMID- 11307905
TI  - Laser cordotomy versus radiotherapy: an objective cost analysis.
AB  - This study presents a cost analysis of and comparison between laser cordotomy and
      external beam irradiation for the treatment of early glottic carcinoma. It
      compares the curative results of the two modalities from data of a retrospective
      study at my institution and a literature review of published cure rates. It also
      reviews the results of objective voice assessments in cases representing both
      treatments. The findings of this study indicate that the cure rates are
      equivalent and that voice quality obtained after laser cordotomy is comparable to
      that obtained after irradiation, yet the total cost of external beam radiotherapy
      is significantly higher than that of laser surgery. Hence, the findings of this
      study provide strong support for initially treating early glottic tumors with
      laser surgery.

PMID- 11307906
TI  - Stellate cells in the human vocal fold.
AB  - Cells have been discovered that are star-like in appearance and that actively
      synthesize extracellular matrices in the human adult vocal fold mucosa. These
      cells have no nomenclature and are thus designated as vocal fold stellate cells
      (VFSC) in this study. Light and electron microscopic investigation of VFSC in the
      human vocal fold mucosa was carried out on excised human adult larynges. A
      comparison between VFSC and conventional fibroblasts was made. The results are
      summarized as follows. 1) The VFSC are distributed in human adult maculae flavae.
      2) The VFSC are irregular and stellate in shape, possessing slender cytoplasmic
      processes. 3) Lipid droplets are present in the cytoplasm. 4) The VFSC have a
      small nucleus-cytoplasm ratio and well-developed rough endoplasmic reticulum,
      suggesting active protein synthesis in these cells. 5) No basal lamina is
      present, and filaments can be seen in the cytoplasm. 6) The VFSC show strong
      cytoplasm staining with periodic acid-Schiff stain and type III collagen. 7) The
      VFSC actively synthesize collagenous fibers, including reticular fibers, as well
      as other extracellular matrices, such as elastic fibers and glycosaminoglycan
      (hyaluronic acid). 8) The VFSC, first demonstrated in this study, actively
      synthesize extracellular matrices in the human adult vocal fold mucosa under
      normal conditions. 9) The VFSC participate in the metabolism of the extracellular
      matrices essential for the viscoelastic properties of the lamina propria of the
      human adult vocal fold mucosa as a vibrating tissue.

PMID- 11307907
TI  - Assessment of vestibular schwannoma growth: application of a new measuring
      protocol to the results of a longitudinal study.
AB  - This study pertains to a group of 44 patients with unilateral vestibular
      schwannoma who did not undergo surgery. Prospectively, the dimensions of the
      tumor were depicted at regular intervals by means of magnetic resonance imaging
      and then judged independently by an otolaryngologist and a neuroradiologist.
      Retrospectively, the size of the tumor was quantified by measuring the maximum
      surface of the lesion in the axial plane. The retrospective surface measurements
      confirmed the assessments made in the prospective part of the study: growth in
      18% of the patients and shrinkage in 7%; 75% remained unchanged. This approach is
      a pragmatic means to determine whether the size of a tumor has changed over the
      course of time.

PMID- 11307908
TI  - Aneurysmal bone cyst in the sphenoid bone: treatment with minimally invasive
      surgery.
AB  - Aneurysmal bone cysts are vascular lesions that destroy and expand bone. We
      report a recently treated case of an aneurysmal cyst of the sphenoid bone. A 14
      year-old girl presented with frontal headaches, bouts of nausea, and vomiting.
      Computed tomography and magnetic resonance imaging showed typical features of an
      aneurysmal bone cyst. Arterial embolization was undertaken before surgery. The
      endoscopic transnasal procedure used allowed the complete removal of the
      aneurysmal bone cyst. This use of minimally invasive surgery makes this case of
      interest to surgeons of the skull base and sinuses.

PMID- 11307909
TI  - Transnasal treatment of congenital choanal atresia with the KTP laser.
AB  - This retrospective analysis presents a minimally invasive method for a transnasal
      approach to treat bilateral and unilateral choanal atresia and stenosis in
      infants and children. We describe an advanced surgical technique that applies the
      use of a KTP laser and give recommendations for preoperative diagnosis and
      postoperative assessment. We report 13 cases of bilateral and unilateral choanal
      atresia or stenosis treated over a 3 1/2-year period. We used a transnasal
      approach and endoscopic control. For bilateral choanal atresia, the operation was
      performed within the first few days of birth. For unilateral choanal atresia or
      stenosis, surgery was performed several weeks after birth. In all cases, an
      intranasal stent was inserted. Our findings demonstrate that this transnasal
      approach provides significant benefits. A primary advantage is the diminished
      risk of intraoperative or postoperative complications. Additional benefits
      include lower rates of re-obstruction and a decreased incidence of subsequent
      disease, including chronic secretory otitis media.

PMID- 11307910
TI  - Epidermal inclusion cyst versus thyroglossal duct cyst: sistrunk or not?
AB  - Epidermal inclusion cyst (EIC) is a recognized cause of an anterior neck mass in
      children. Controversy exists as to the proper surgical management of an anterior
      neck EIC: is simple excision adequate treatment, or is a Sistrunk procedure
      necessary? A retrospective review of the operative logs of the two senior authors
      (M.M.A., R.F.W.) from 1993 to the present revealed 16 children, ages 6 months to
      9 years (mean, 4.5 years), with a diagnosis of anterior neck EIC. An accurate
      intraoperative diagnosis of an EIC in all cases allowed for a simple excision of
      the mass rather than a Sistrunk procedure. The final histologic diagnosis was EIC
      in all 16 patients. Follow-up of these 16 patients for a mean of 4.5 years
      revealed no recurrences or complications. When the diagnosis of EIC can be made
      confidently in the operating room, simple excision is an adequate surgical
      treatment.

PMID- 11307911
TI  - Pediatric tracheotomy: is postoperative chest X-ray necessary?
AB  - A retrospective study of 101 children who underwent tracheotomy at the Children's
      Hospital of Pittsburgh from 1993 to 1996 was performed. The following criteria
      were reviewed in each patient: age, gender, race, prematurity, weight during
      tracheotomy, presence of preoperative airway support, duration of tracheotomy,
      nature (emergent versus elective), tracheotomy tube size, reason for tracheotomy,
      accompanying medical diagnoses, chest x-ray (CXR) findings, surgical service,
      postoperative symptoms (up to 3 days), and operative mortality rate. Of these
      criteria, our results show that CXR-screenable complications occurred in patients
      who underwent emergent recannulation, as well as those who exhibited ventilatory
      distress (oxygen saturation level of <90%) and specific changes in postoperative
      symptoms. Pneumothorax developed after tracheotomy in 3 of the 101 patients; each
      had one of these risk factors. We conclude that CXR of all pediatric patients
      after tracheotomy may be unnecessary with the use of flexible endoscopy and
      screening restrictions that are both health-conscious and cost-effective.

PMID- 11307912
TI  - Concurrent glottic and tracheal stenoses: restoration of airway continuity in end
      stage malignant disease.
AB  - Six patients known to have inoperable esophageal carcinoma presented with stridor
      due to both malignant tracheal stenosis (with additional respiratory-digestive
      tract fistula in 2 patients) and bilateral vocal cord paralysis. Patency was
      restored by endotracheal stenting plus unilateral cordotomy. Four patients had
      immediate relief. Two patients required enlargement of the vocal cord incision.
      One of them declined reoperation and underwent tracheostomy. The stent function
      was uneventful, with no dislodgment or mucus impaction. The fistula seal was
      complete, with no aspiration through the newly shaped glottic orifice. The peak
      expiratory flow increased from 24.4% +/- 9.7% of predicted normal before the
      procedure to 40.5% +/- 13.7% after the procedure. Restoration of airway
      continuity in serial laryngotracheal stenoses by a combined approach is a
      feasible technique in end-stage cancer patients. It effectively relieves
      respiratory distress and ensures voice preservation. In addition, it may avoid
      the risks of tracheotomy.

PMID- 11307913
TI  - Epidemiological studies on hearing impairment with reference to genetic factors
      in Sichuan, China.
AB  - Hearing impairment is the most common disorder of sensorineural function and is
      an economically and socially important cause of human morbidity. A large-scale
      epidemiological survey of hearing loss was conducted with 126,876 unselected
      subjects (63,741 male and 63,135 female) from Sichuan, China. The overall
      prevalence of hearing loss was 3.28% (4,164 of 126,876), and the prevalence
      increased with age, reaching 12.8% (1,465 of 11,421) at 60 years of age. In
      73.03% of all cases (3,041 of 4,164), the hearing loss was sensorineural, and in
      20.39% (849 of 4,164), it was conductive; the remaining cases (6%) were mixed
      hearing loss. Bilateral loss was found in 74.5% of cases (3,103 of 4,164). In
      63.79% of cases (2,656 of 4,164), the degree of hearing loss was less than 55 dB
      hearing level (HL), and in 5.67% of cases (236 of 4,164), it was greater than 90
      dB HL. The prevalence of hearing loss in childhood (<15 years of age) was 0.67%
      (227 of 34,157), of which 57.7% of cases were conductive and 38.8% were
      sensorineural. The prevalence of genetic hearing loss was 0.28% (349 of 126,876).
      Persons who lived in the flatlands appeared to have a higher prevalence than
      those who lived in the hills. Several ethnic groups, including Tibetans, the Yi,
      and the Lisu, had a higher prevalence of hearing loss. Presbycusis, otitis media,
      and genetic factors were the most commonly recognized causes of hearing
      impairment overall, but otitis media and genetic factors were the main causes of
      hearing loss in children. Causes for the observed differences in prevalence and
      etiologic factors between China and industrialized countries will be discussed.
      In China, infections and genetic factors appear to be of major importance as
      causes of hearing loss.

PMID- 11307914
TI  - Incidence of pharyngeal hypophysis in neonates a histologic study.
AB  - The presence of adenohypophysial tissue in the nasopharynx is no longer disputed.
      This study was performed in 50 neonatal cadavers subjected to medical autopsy
      within 6 hours of death. The aim was to study the incidence of extrasellar
      pituitary tissue in the nasopharynx and its various histologic cell types. The
      transpalatal approach was used to obtain the specimens. The specimens were
      stained with hematoxylin and eosin and periodic acid-Schiff-orange G for
      selective demonstration of adenohypophysial cells. Histopathologic evaluation led
      to the detection of pituitary tissue in 16% of the examined specimens. Selective
      staining demonstrated a 6% positive incidence of adenohypophysial cells. The
      pharyngeal hypophysis exists in 2 forms: a typical adenohypophysial collection of
      cells and an atypical subepithelial cluster. The incidence of hypophysial tissue
      was higher in the older neonates, perhaps because of hormonal stimulation of the
      caudal remnant of Rathke's pouch.

PMID- 11307915
TI  - Malignant melanoma arising within a burn scar case report and review of the
      literature.
AB  - Burn scar carcinomas, also called Marjolin's ulcers, are uncommon tumors that
      arise from an antecedent burn. Most burn scar carcinomas are diagnosed about 30
      years after the burn, and most are well-differentiated squamous cell carcinomas.
      We report a case in which a squamous cell carcinoma developed within a burn scar
      on the cheek and then a malignant melanoma arose within the burn scar after the
      squamous cell carcinoma had been excised. We also review the available literature
      on burn scar carcinoma, covering the demographics, pathogenesis, diagnosis,
      prognosis, and treatment of the disease. Given the multifocality of this disease
      process, we advocate aggressive resection of the entire burn scar, as well as the
      tumor, to prevent the development of further cancers within the wound.

PMID- 11307916
TI  - Fungal malignant otitis externa due to Scedosporium apiospermum.
AB  - Malignant otitis externa (MOE) is an infection of the external auditory canal
      that invades the skull base. Aspergillus species fungi were the pathological
      organism in 21 of 23 reported cases of fungal MOE. We report on a 21-year-old man
      with end-stage acquired immunodeficiency syndrome (AIDS) and fungal MOE caused by
      Scedosporium apiospermum. Fungal MOE is most common in patients with end-stage
      AIDS and hematologic malignancies. Granulation tissue is not a common finding in
      these patients, and the infectious process often starts in the mastoid air cells
      or middle ear space, as opposed to the external auditory canal. Surgical
      debridement and amphotericin B are the mainstays of therapy; resolution of the
      infection depends greatly on the severity of the underlying disease.

PMID- 11307917
TI  - Bilateral chylothorax following neck dissection: a new method of treatment.
AB  - Chylothorax is a serious condition with a high rate of morbidity that may lead to
      death. Although it is encountered more frequently with certain thoracic
      procedures, it is considered to be a rare complication of neck dissection.
      Different forms of management have been postulated; however, no consensus of
      treatment has been achieved. A case of severe bilateral chylothorax that
      developed after bilateral neck dissection in a patient with laryngeal carcinoma
      is presented. Somatostatin injection was successful after total parenteral
      nutrition failed to control the chylothorax. On the basis of this case and the
      review of the literature discussed here, we advocate the use of somatostatin with
      other conservative measures in the management of chylothorax.

PMID- 11307918
TI  - Non-inflatable sterile sheath for introduction of the flexible
      nasopharyngolaryngoscope.
AB  - Since the inception of the flexible nasopharyngolaryngoscope, sterility has been
      a primary concern. The increased incidence of hepatitis, tuberculosis, and
      acquired immunodeficiency syndrome has raised the fear of cross-contamination.
      Sterilization requires the use of ethylene oxide, which is economically
      disadvantageous, forcing most practitioners to disinfect rather than sterilize
      their nasopharyngolaryngoscopes. A presterilized, disposable sheath was designed
      in 1993. The system was cumbersome, because it required an air pump. Thus, it was
      not adopted by the majority of physicians. As a result, the manufacturer
      developed a new system, which I evaluated. It is cost-effective, smoother
      surfaced, 70% thinner-walled, and much simpler to use. The disposable, single-use
      sheath is sterile, with no need for a pump or any additional device, and can be
      used anywhere at any time. I believe it will become the standard method for
      sterile introduction of the nasopharyngolaryngoscope.

PMID- 11307919
TI  - Does cochlear nerve aplasia always occur in the presence of a narrow internal
      auditory canal?

PMID- 11307920
TI  - Decreased concentration of serum apolipoprotein C-III in cows with fatty liver,
      ketosis, left displacement of the abomasum, milk fever and retained placenta.
AB  - Apolipoprotein (apo) C-III is a low molecular mass protein mainly distributed in
      the high-density lipoprotein (HDL) fraction. In cows with postparturient diseases
      such as ketosis, concentrations of cholesterol, phospholipids and apoA-I and the
      activity of lecithin:cholesterol acyltransferase, which are mainly distributed in
      or functionally associated with HDL, are reduced. The purpose of the present
      study was to examine whether the serum concentration of apoC-III was similarly
      decreased in the postparturient diseases. Compared with healthy controls, the
      apoC-III concentration was significantly (P<0.01) decreased in cows with fatty
      liver, ketosis, left displacement of the abomasum, milk fever and retained
      placenta. Concentrations of apoC-III in the HDL fractions from diseased cows were
      also lower than in controls. Of the diseased cows, the decreased apoC-III
      concentration was particularly distinct in cows with milk fever. Increased
      nonesterified fatty acid and reduced free cholesterol, cholesteryl ester and
      phospholipid concentrations were observed in cows with milk fever, as in the
      other diseased cows. The decrease in the apoC-III concentration is suggested to
      be closely associated with the postparturient disorders, in particular with milk
      fever.

PMID- 11307921
TI  - Detection of Cryptosporidium parvum oocysts in environmental water in Hokkaido,
      Japan.
AB  - Control of cryptosporidiosis is important in public health. Rivers that are
      polluted with Cryptosporidium and drinking water that is treated for drinking
      water production from polluted rivers could result in the waterborne disease of
      cryptosporidiosis. We carried out an epidemiological study of natural water
      supplies in Hokkaido, one of the largest dairy prefectures in Japan. To detect
      Cryptosporidium oocysts in environmental water, the filtration method was used
      for 28 samples, which were collected from 10 rivers. A method adapted from the
      United States Environmental Protection Agency (U.S. EPA) filtration method using
      a cartridge filter has been used for the collection of samples. Oocysts were
      separated from a pellet by discontinuous sucrose gradient method. Twelve samples
      were collected from 10 rivers and parasites were purified by iron (III)
      flocculation method. Cryptosporidium parvum oocysts were identified with the
      immunofluorescence antibody technique using DIF kit (Cellabs Pty. Ltd.,
      Sydney/Australia). We detected Cryptosporidium oocysts in 6 out of 10 rivers
      sampled. Fifty percentage (14/28) of the samples were Cryptosporidium-positive.
      The average number of Cryptosporidium oocysts was 16.73/100 L (max. 80/100 L).

PMID- 11307922
TI  - Analysis of the epitopes on staphylococcal enterotoxin A responsible for emetic
      activity.
AB  - To identify which region of staphylococcal enterotoxin A (SEA) is responsible for
      the emetic activity, twelve synthetic peptides corresponding to the entire SEA
      amino acid sequence and their respective anti-peptide antibodies were prepared
      and tested. The anti-peptide antibodies were tested for neutralization of SEA
      induced emesis in Suncus murinus (Shrew mouse). The results indicate that SEA
      induced emesis was neutralized by the mixture of three anti-peptide antibodies to
      A-7 (corresponding to amino acid residues 121-140), A-8 (141-160) and A-9 (160
      180). These findings suggest that the regions corresponding to residues 121-180
      may be the epitopes responsible for the emetic activity of SEA.

PMID- 11307923
TI  - Association between exogenous atrial natriuretic peptide and hemodynamics in dogs
      with congestive heart failure produced by experimental mitral regurgitation.
AB  - Association between exogenous atrial natriuretic peptide (ANP) and hemodynamic
      changes was ascertained in 3 dogs with overt congestive heart failure (CHF(+))
      and 3 dogs without congestive heart failure (CHF(-)) caused by experimental
      mitral regurgitation (MR). The hemodynamic measurements were recorded in all dogs
      during and after 1 hr infusion of ANP at the rate of 0.1 (low dose), 0.5 (medium
      dose) and 1.0 (high dose) microg/kg/min, respectively. Heart rate, mean arterial
      pressure, pulmonary capillary wedge pressure (PCWP) and systemic vascular
      resistance decreased significantly during and after ANP infusion even with low
      dose in the CHF(+). Stroke volume, stroke volume index and cardiac output in the
      CHF(+) during and after ANP infusion showed an increasing trend as compared with
      the CHF(-). Double product, an indicator of myocardial oxygen consumption,
      significantly decreased during and after ANP administration at all doses in the
      CHF(+). These findings indicate that even at low dose, exogenous ANP improves
      cardiac performance and reduces myocardial oxygen consumption in the CHF(+), and
      suggest that ANP has beneficial effects in the treatment of dogs with overt
      congestive heart failure resulting from MR.

PMID- 11307924
TI  - Bee venom pretreatment has both an antinociceptive and anti-inflammatory effect
      on carrageenan-induced inflammation.
AB  - Although the injection of bee venom (BV) has been reported to evoke tonic pain
      and hyperalgesia, there is conflicting evidence in the literature indicating that
      BV can also exert an anti-inflammatory and antinociceptive effects on
      inflammation. In this regard, BV has been traditionally used in Oriental medicine
      to relieve pain and to treat chronic inflammatory diseases such as rheumatoid
      arthritis. The present study was designed to test the hypothesis that BV induces
      acute nociception under normal conditions, but that it can serve as a potent anti
      inflammatory and antinociceptive agent in a localized inflammatory state. The
      experiments were designed to evaluate the effect of BV pretreatment on
      carrageenan (CR)-induced acute paw edema and thermal hyperalgesia. In addition,
      spinal cord Fos expression induced by peripheral inflammation was quantitatively
      analyzed. In normal animals subcutaneous BV injection into the hindlimb was found
      to slightly increase Fos expression in the spinal cord without producing
      detectable nociceptive behaviors or hyperalgesia. In contrast pretreatment with
      BV (0.8 mg/kg) 30 min prior to CR injection suppressed both the paw edema and
      thermal hyperalgesia evoked by CR. In addition, there was a positive correlation
      between the percent change in paw volume and the expression of Fos positive
      neurons in the spinal cord. These results indicate that BV pretreatment has both
      antinociceptive and anti-inflammatory effects in CR-induced inflammatory pain.
      These data also suggest that BV administration may be useful in the treatment of
      the pain and edema associated with chronic inflammatory diseases.

PMID- 11307925
TI  - Aberrant expression of cyclin D1 in pulmonary proliferative lesions induced by
      high doses of urethane in transgenic mice carrying the human prototype c-H-ras
      gene.
AB  - In our previous study, when rasH2 mice and non-transgenic (non-Tg) littermates
      were injected intraperitoneally with 1,000 mg/kg of urethane once or three times
      at two-day intervals, the incidence of lung proliferative lesions in rasH2 mice
      given triple doses of urethane was significantly increased, compared to that in
      rasH2 mice given a single dose of urethane, and the mutation frequency of the
      transgene in lung tumors in rasH2 mice given triple doses was lower than that in
      rasH2 mice given a single dose of urethane. In the present study, differential
      immunohistochemical expressions of Cyclin D1 and PCNA, that lead to abnormal cell
      proliferation and tumor development due to uncontrolled G1-S transition in the
      cell cycle, as well as p53 tumor suppressor gene in pulmonary proliferative
      lesions obtained from our previous study were investigated. Over-expression of
      Cyclin D1 in hyperplasias in rasH2 mice given triple doses was significantly
      increased, compared to that in the single-injection group, but no significant
      differences in Cyclin D1 between the single and triple injection groups were
      observed in hyperplasias in non-Tg mice or lung tumors in either rasH2 or non-Tg
      mice. There were no differences in the PCNA labeling index of hyperplasias in
      rasH2 or non-Tg mice between the triple-injection and single-injection groups,
      while the PCNA labeling index tended to be increased in the tumor, compared with
      that in hyperplasias. There was neither mutation of p53 nor an increase in
      immunoreactivity of wild type p53 in these proliferative lesions. These results
      suggest that cyclin D1 over-expression in alveolar/bronchiolar hyperplasias in
      rasH2 mice in the triple-injection group is not only indicative of a high cell
      proliferation rate but also of an important role in the process of malignant
      transformation.

PMID- 11307926
TI  - Enhanced phagocytic activity of neutrophils caused by administration of egg white
      derivatives (EWD) in cats injected with cyclophosphamide (CPA).
AB  - To examine in vivo effects of egg white derivatives (EWD), the numbers of
      peripheral blood cells and neutrophil phagocytosis were evaluated in cats
      injected intramuscularly with cyclophosphamide (CPA). There were no changes in
      the number of red blood cells (RBC) or packed cell volume (PCV) values regardless
      of oral administration of EWD or injection of CPA, but the numbers of platelets,
      white blood cells (WBC) and neutrophils in cats administered EWD significantly
      increased (p<0.05 to 0.01) when compared with those in control cats which
      received saline solution. In addition, the administration of EWD resulted in a
      significant enhancement in the phagocytic activity of neutrophils (p<0.01) when
      compared to control cats, suggesting that EWD has a stimulating effect on
      leukocyte progenitors. The numbers of platelets, WBC and neutrophils, and the
      phagocytic activity of neutrophils in cats injected with CPA alone were
      significantly lower (p<0.05 to 0.01) than those in control cats. However, co
      administration of EWD to cats injected with CPA resulted in a significant
      increase in the numbers of platelets, WBC and neutrophils (p<0.05 to 0.01), and
      in the phagocytic response of neutrophils (p<0.01) when compared to cats injected
      with CPA alone. Therefore, these results suggest that co-administration of EWD
      may be effective in reducing some possible side effects in animals treated with
      immunosuppressive or antitumor agents.

PMID- 11307927
TI  - Immunization against intestinal bacterial endotoxin prevents alcoholic fatty
      liver in rats.
AB  - Accumulating evidences indicate that an endotoxin originating from intestinal
      gram-negative bacteria may be involved in alcohol-induced liver injury including
      fatty liver. Therefore, whether immunization against intestinal bacterial
      endotoxin blocked fatty liver induced by chronic alcohol and diet including much
      unsaturated fatty acid was investigated in rats. The titer of antibody against
      the endotoxin increased significantly after 13 weeks of continuous immunization.
      Daily alcohol treatment was initiated at 12 weeks and continued for 4 weeks.
      Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase
      (GOT) and triglyceride (TG) levels increased significantly in non-immunized rats
      receiving alcohol, but not in immunized rats. Continuous alcohol treatment
      gradually decreased the survival rate to 60% from 13 days after beginning
      administration in non-immunized, but not immunized, rats. A histochemical study
      revealed that continuous treatment with alcohol and unsaturated fatty acids
      caused fatty liver in non-immunized, but not immunized, rats. This study strongly
      supports the hypothesis that alcohol-induced fatty liver is due to a circulating
      endotoxin, and suggests that immunization for endotoxin prevent the alcoholic
      fatty liver.

PMID- 11307928
TI  - Adsorption effect of activated charcoal on enterohemorrhagic Escherichia coli.
AB  - The adsorption property of activated charcoal on verotoxin (VT)-producing
      Escherichia coli (VTEC) was examined using E. coli O157:H7. In the present study,
      E. coli O157:H7 strains were effectively adsorbed by activated charcoal.
      Adsorption was dose-dependent, and the maximum adsorption occurred within 5 min.
      At 10 mg of activated charcoal, bacteria tested were completely adsorbed.
      Activated charcoal also had the capacity to adsorb toxin (verotoxin 2) activity
      from the bacterial extract. Furthermore, the adsorption efficiency of activated
      charcoal for the normal bacterial flora in the intestine was assessed using
      Enterococcus faecium, Bifidobacterium thermophilum, and Lactobacillus
      acidophilus. Activated charcoal showed lower binding capacity to the normal
      bacterial flora tested than that to E. coli O157:H7 strains. These results
      suggest that activated charcoal could be a good adsorbent system for the removal
      of VTEC and verotoxin.

PMID- 11307929
TI  - Electron microscopic cytochemical studies of anionic sites in the rat spleen.
AB  - The distribution patterns of the intensity of negative charge on the free
      surfaces (glycocalyx of the plasma membrane) of endothelial cells (ECs) in blood
      vessels and reticular cells (RCs) in the splenic cord of the rat spleen were
      studied by an electron microscopic cytochemical method using polyethyleneimine
      (PEI) as a cationic probe. Spleens from adult male rats were perfusion-fixed with
      0.5% glutaraldehyde -4% paraformaldehyde containing 0.05% cetylpyridinium
      chloride and then perfused with 0.5% PEI at pH 7.4. On the free surfaces
      (glycocalyx of the plasma membrane) of the ECs examined, distinct PEI-positive
      reactions were observed in blood vessels, such as trabecular arteries, central
      arteries, arterial capillaries, pulp veins and trabecular veins. These PEI
      positive electron-dense substances in the trabecular arteries, central arteries,
      and trabecular veins took the shape of a band of 170-250 nm in thickness. On the
      other hand, the corresponding ultrastructure of the ECs lining the splenic
      sinuses and the RCs in the splenic cord showed exceedingly weak PEI reactions.
      The PEI-reactive deposits were significantly thinner than those in the above
      blood vessels. As the thickness of the electron-dense substances can be related
      to the density of the negative charge, these results suggest that there is a high
      intensity of negative charge on the free surfaces (glycocalyx of the plasma
      membrane) of ECs in blood vessels where blood cells and plasma pass into the red
      pulp or are discharged from the red pulp. In contrast, the splenic sinuses and
      RCs, which are the main components of the red pulp, contain weakly negative
      charged sites. This may contribute to the microcirculation of the splenic blood
      vessels and elucidate the possible physiological functions of the spleen, such as
      blood storage.

PMID- 11307930
TI  - Reproductive pattern of the sun bear (Helarctos malayanus) in Sarawak, Malaysia.
AB  - Fecal progesterone assays were conducted in 3 captive female sun bears (Helarctos
      malayanus) segregated from males to characterize the species-specific
      reproductive pattern in their original distribution area in Sarawak, Malaysia.
      Peaks of fecal progesterone concentrations were observed once annually, and
      lactation was observed after increasing progesterone concentrations in all
      females without mating stimulus. These results suggest that sun bears in Sarawak,
      Malaysia, may have a seasonal reproductive pattern and ovulation was noted to
      occur spontaneously, followed by pseudopregnancy.

PMID- 11307931
TI  - Immunohistochemical analysis of molecular events in tubulo-interstitial fibrosis
      in a mouse model of diffuse mesangial sclerosis (ICGN strain).
AB  - Diffuse mesangial sclerosis (DMS) is one of the hereditary glomerular diseases
      and histologically characterized by severe glomerulosclerosis and subsequent
      tubulo-interstitial fibrosis (TIF). In DMS patients, renal dysfunction correlates
      well with TIF, rather than with glomerular lesions. Thus, molecular mechanisms
      whereby TIF in DMS progresses should be addressed. Previously, we found that
      nephrotic ICGN mice manifest DMS-like lesions and develop renal dysfunction in
      accordance with onset of TIF. In the present study, we investigated fibrogenic
      events involved in the progression of TIF after DMS manifestation, using the DMS
      mouse model. Immunohistochemistry revealed that expression of transforming growth
      factor-beta (TGF-beta) was rare in the interstitial cells of the nephrotic mice
      at the early-stage of DMS, while the TGF-beta expression became evident in the
      late-stage DMS mice. Platelet-derived growth factor (PDGF) was mildly expressed
      in the distal tubules of the early-stage DMS mice, whereas the PDGF expression
      markedly increased at the late-stage of DMS. As a result, alpha-actin-positive
      myofibroblastic cells were found dominant in the interstitial spaces of the late
      stage DMS mice. Finally, TIF became severe in accordance with the overexpressions
      of these molecules. Our results suggest that in our murine model: 1) persistent
      proteinuria leads to over-expression of TGF-beta and PDGF in non-glomerular
      areas; 2) these cytokines provoke interstitial myofibroblast accumulation; and 3)
      the myofibroblasts produce fibrotic matrix proteins in the interstitial spaces.
      This process may possibly contribute to the development of TIF in DMS patients.

PMID- 11307932
TI  - Beta 3-adrenergic agonist up-regulates uncoupling proteins 2 and 3 in skeletal
      muscle of the mouse.
AB  - Chronic stimulation of the beta3-adrenergic receptor (AR) in obese animals
      resulted in a reduced adiposity associated with an increased expression of
      thermogenic uncoupling protein (UCP)1 in adipose tissues. In this study, the mRNA
      expression of newly cloned UCP isoforms (UCP2 and UCP3) were examined in obese
      yellow KK and C57BL control mice. UCP2 mRNA was found in all tissues examined,
      with higher levels in adipose tissues and skeletal muscle of the obese mice. UCP3
      mRNA was expressed in skeletal muscle, heart and brown adipose tissue similarly
      in the two mouse strains. Daily injection of a selective beta3-adrenergic
      agonist, CL316,243 (0.1 mg/kg), for 10 days resulted in a marked reduction of
      white fat pad weight and 1.8-4.8-fold increase in the mRNA levels of UCP2 and
      UCP3 in skeletal muscle of obese mice. No noticeable change in the UCP2 and 3
      mRNA levels was found in brown and white adipose tissues. It was also found that
      CL316,243 injection produced a marked and sustained elevation of the plasma free
      fatty acid level. These results, together with our previous findings of the fatty
      acid-induced UCP expression in a myocyte cell line in vitro, suggest that the
      beta3-AR agonist-induced UCP expression in skeletal muscle may be mediated
      through the elevated plasma free fatty acids. It was also suggested that anti
      obesity effect of beta3-AR agonists is attributable to increased thermogenesis
      not only by UCP1 but also by UCP2 and UCP3.

PMID- 11307933
TI  - An investigation of heavy metal exposure and risks to wildlife in the Kafue flats
      of Zambia.
AB  - Exposure and ecological risks to heavy metals (copper, zinc, manganese, iron) at
      Lochnivar and Blue Lagoon National Parks in wildlife dependent on the Kafue river
      contaminated with mining waste was evaluated. Samples included water, fish,
      grasses and Kafue Lechwe (Kobus leche kafuensis) liver. At both parks copper
      ranged from 0.03-0.04 mg/l; 3.0-6.0 mg/kg; 11.0-44.0 mg/kg; trace -199.0 mg/kg;
      while zinc was 0.01 mg/l; 32.0-82.0 mg/kg; 15.0-21.0 mg/kg; and 52.0-138.0 mg/kg;
      in water, fish, grasses and lechwe, respectively. Manganese ranges were 0.15-0.16
      mg/l; 7.0-18.0 mg/kg; 51.0-145.0 mg/kg; and 40.0-53.0 mg/kg while iron ranges
      were 0.13-0.14 mg/l; 26.0-134.0 mg/kg; 1766.0-1797.0 mg/kg; and 131.0-856.0
      mg/kg; in water, fish, grasses and lechwe, respectively. Levels in all samples
      except water were high indicating potential for adverse effects.

PMID- 11307934
TI  - Infectivity and oocyst excretion patterns of Cryptosporidium muris in slightly
      infected mice.
AB  - To determine the infectivity of Cryptosporidium to hosts in slight infections, we
      examined the infectivity and oocyst output patterns of Cryptosporidium muris in
      mice inoculated with small numbers of oocysts. One of the 25 ICR mice inoculated
      with 2.4 x 10(1) oocysts and 19 of the 25 mice inoculated with 2.4 x 10(2)
      oocysts shed oocysts in the feces after inoculation. Four of the 50 mice
      inoculated with 2.4 x 10(1) oocysts for 10 consecutive days also shed oocysts and
      their OPG values were similar to that of the mice which received 2.4 x 10(2)
      oocysts. Consequently, it is clear that less than 10% of the mice which received
      2.4 x 10(1) C. muris oocysts for 10 consecutive days.

PMID- 11307935
TI  - Expression of Kit, the receptor for stem cell factor, in bovine peripheral blood.
AB  - The expression of Kit, the receptor for stem cell factor (SCF), on bovine
      peripheral blood cells (PBCs) was examined by using monoclonal antibodies against
      the bovine Kit protein. Flow cytometric analysis showed that approximately 1.5%
      of PBCs expressed Kit. In cytospin preparations, the morphology of most Kit+ PBCs
      was similar to that of large lymphocytes. Subsets of Kit+ PBCs coexpressed CD3,
      IgM, and/or CD11b but not CD14 or G1. SCF did not induce the proliferation of
      Kit+ PBCs in vitro. These results indicate that Kit is expressed on subsets of
      lymphocytes in bovine peripheral blood, but the ligand of Kit, SCF, does not
      directly induce the proliferation of this cell population.

PMID- 11307936
TI  - Effects of salivary gland extract from Rhipicephalus sanguineus on immunoglobulin
      class productivity of canine peripheral blood lymphocytes.
AB  - Effects of salivary gland extract (SGE) from Rhipicephalus sanguineus on
      immunoglobulin class productivity of canine peripheral blood lymphocytes (PBL) in
      vitro were studied. The detectable limit of the ELISA for canine total
      immunoglobulin, IgM and A was at least 1, 1 and 15 ng/ml, respectively, and it
      seems to be useful for the evaluation of non-specific immunoglobulin class
      productivity in vitro. SGE from R. sanguineus suppressed pokeweed mitogen- or
      lipopolysaccharide-induced total immunoglobulin and IgA productivity of canine
      PBL although IgM productivity was not suppressed. These results suggested that
      the suppression was caused partly by the direct effect of SGE on B lymphocytes.

PMID- 11307937
TI  - Survey of arthroscopic surgery for carpal chip fractures in thoroughbred
      racehorses in Japan.
AB  - Medical and racing records of 155 Thoroughbred racehorses that underwent
      arthroscopic surgery for carpal chip fractures were investigated. Articular
      damage for 98.4% of the fractures was classified as G1 or G2 using McIlwraith's
      criteria. The rate of return to racing after surgery was 82.6%. Evaluation of
      racing performance after surgery was attempted using a placing index (PI) based
      on race finish position. There was no significant difference in the PI
      distribution between horses that underwent surgery and other healthy horses.

PMID- 11307938
TI  - Malignant fibrous histiocytoma (MFH) cells and macrophages/histiocytes have a
      common antigen recognized by a monoclonal antibody risen against a rat MFH
      derived cloned cell line.
AB  - A monoclonal antibody (B9) was generated by using a rat malignant fibrous
      histiocytoma (MFH)-derived cloned cell line (MT-8) as the immunogen.
      Immunohistochemically, B9 reacted specifically with a cytoplasmic antigen of MT-8
      cells. Furthermore, B9 immunolabeled another MFH-derived cloned cells (MT-9) and
      histiocytic sarcoma cells, as well as macrophages/histiocytes in normal and
      diseased tissues of rats. These findings suggest the presence of a common antigen
      recognized by B9 between MFH cells and macrophages/histiocytes. This suggests
      that MFH cells may express histiocytic nature.

PMID- 11307939
TI  - Effect of supplementation of dry cat food with D,L-methionine and ammonium
      chloride on struvite activity product and sediment in urine.
AB  - Feeding dry foods supplemented with urine acidifier (D,L-methionine (Met) or
      ammonium chloride) decreased urinary pH and struvite activity product in
      clinically normal cats. As a result, the number of struvite crystals in urine was
      greatly reduced. Supplementation with 3% Met but not 1% Met caused decrease in
      the urinary concentration of sediment, which resulted from a reduction in the HCl
      soluble fraction. The concentration of HCl-insoluble sediment was not affected by
      supplementation with the urine acidifier.

PMID- 11307940
TI  - Antimicrobial susceptibility of Actinobacillus pleuropneumoniae isolated from
      pigs in Korea using new standardized procedures.
AB  - The in vitro susceptibilities of 76 isolates of Actinobacillus pleuropneumoniae
      collected from pigs with pleuropneumonia were tested with 12 commonly used
      antimicrobial drugs by an agar dilution minimal inhibitory concentration
      procedure according to National Committee for Clinical Laboratory Standards
      (NCCLS) guidelines. Field isolates had low MICs for ceftiofur, danofloxacin and
      penicillin. No correlation of antimicrobial resistance was related to serotype.

PMID- 11307941
TI  - Determination of canine beta2-microgloblin in plasma and urine by enzyme-linked
      immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay was developed for the determination of
      canine beta2-microglobulin (beta2-m) in plasma and urine. The detectable
      sensitivity for pure canine beta2-m was 0.05 microg/l and the analytical range
      was 0.1 to 50 microg/l. The mean analytical recovery when pure canine beta2-m was
      added to normal plasma was 101.9%. The mean analytical recovery in the urine was
      102.1%. The intra-day variation coefficient was 3.1% in plasma, 4.3% in serum and
      1.9% in urine. No difference was found between the concentration of beta2-m in
      plasma and serum (n=17). The concentration of beta2-m in the plasma of normal
      dogs was 1.82 +/- 0.57 mg/l (n=31). The mean excretion in 24 hr urine collected
      from normal dogs was 17.6 +/- 9.2 microg/l, 0.22 +/- 0.12 microg/kg of body
      weight or 14.2 +/- 9.4 microg/g of urine creatinine. The beta2-m creatinine index
      of random urine samples was 23.5 +/- 16.6 microg/g (n=26). There was a close
      correlation between the beta2-m creatinine index of 24 hr urine samples and that
      of random urine samples (r=0.872).

PMID- 11307942
TI  - Induction of primer pheromone production by dihydrotestosterone in the male goat.
AB  - Castrated goats were treated with dihydrotestosterone (DHT) for four weeks. Skin
      samples were collected from the head and the rump regions before and after the
      DHT treatment. The primer pheromone activities of these samples were assessed
      neurophysiologically by recording electrophysiological manifestations of the
      hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity.
      Pheromone activity was detected in both the head and rump skin samples following
      the DHT treatment, although the development of sebaceous glands was limited to
      the head region. Taken together with our previous finding that testosterone
      treatment results in the appearance of primer pheromone activity in the skin
      sample of the head region but not of the rump region. these observations suggests
      that the regional difference of pheromone production would be ascribed to
      intrinsic expression levels of 5alpha-reductase, an enzyme converting
      testosterone to DHT.

PMID- 11307943
TI  - Pneumocystis carinii pneumonia in a Cavalier King Charles Spaniel.
AB  - Pneumocystis carinii pneumonia was diagnosed by postmortem examination of a one
      year-old Cavalier King Charles Spaniel with four-week history of dyspnea.
      Cytologic and histologic examination of lung tissues revealed numerous P. carinii
      trophozoites and cysts, and P. carinii specific DNA was detected by polymerase
      chain reaction. The dog showed hypogammagloblinemia and extremely low levels of
      serum IgG. It was considered that P. carinii pneumonia in this case was
      associated with an immunodeficient condition which has already been reported in
      Miniature Dachshunds.

PMID- 11307944
TI  - Molecular cloning of a cDNA coding for feline liver xanthine dehydrogenase.
AB  - A cDNA coding for feline liver xanthine dehydrogenase (XDH, EC 1.1.204) was
      amplified by RT-PCR and cloned for determining the sequence. The clones contained
      an open reading frame of 4002 base pairs encoding 1333 amino acid residues. The
      calculated molecular weight and isoelectric point were approximately 146 kDa and
      7.0. Comparison of the deduced amino acid sequences indicated remarkable high
      homology, i.e., the amino acid residues of feline XDH shared approximately 90%,
      87%, 87% and 86% identity with those of human, bovine, rat and mouse,
      respectively. The anino acid sequences of two putative iron-sulfur centers, one
      NAD binding site and one molybdenum binding site were well conserved among
      mammalian animals.

PMID- 11307945
TI  - Antimicrobial susceptibility of Staphylococcus intermedius isolated from healthy
      and diseased dogs.
AB  - A total of 90 strains of Staphylococcus intermedius isolated from dogs were
      examined for antimicrobial susceptibility. There were no significant differences
      in the distribution patterns of MICs between strains from 1982 to 1985 and those
      from 1999, and between strains from healthy dogs and those from diseased dogs.
      All of the strains were susceptible to ABPC, DMPPC, CEX, TDM, ERFX, BFLX, and FF
      at concentrations of 0.05 to 6.25 microg/ml. The MICs of OTC, KM, EM, AIV-TS, and
      LCM were distributed in a broad range of 0.1 to >100 microg/ml, indicating the
      existence of resistant as well as susceptible populations of S. intermedius.
      Thirty-three strains (36.7%) were resistant to one or more anitmicrobial agents
      such as OTC (n=32), KM (n=9), EM (n=7), AIV-TS (n=7), and LCM (n=7).

PMID- 11307946
TI  - Oligosaccharides as immunodeterminants of erythropoietin for two sets of anti
      carbohydrate antibodies.
AB  - Antibodies directed against recombinant erythropoietin have been obtained by
      immunization of rabbits with the hormone in Freund's complete adjuvant. Two sets
      of antibodies are present in the serum of the immunized rabbits. The results of
      oxidation of the erythropoietin with periodate, inhibition of the antibodies with
      the structural monosaccharide residues of the hormone, and reaction of the
      antibodies with lectins of known carbohydrate specificity have established the
      antibodies to be anti-carbohydrate antibodies. These antibodies may be of value
      as tracking agents for some diseases and should be useful for detecting abuses of
      the hormone in enhancing performance in athletic competitions.

PMID- 11307947
TI  - Intrinsic tryptophan fluorescence of human serum proteins and related
      conformational changes.
AB  - The unfolding of human serum proteins (HSP) was studied by measuring the
      intrinsic fluorescence intensity at a wavelength of excitation corresponding to
      tryptophan's or typosine's fluorescence and surface hydrophobicity. The maxima
      emission wavelengths (lambdamax) of human serum albumin (HSA) and human serum
      globulin (HSG) before beer consumption (BC) were 336.0 and 337.0 nm and after BC
      shifted to 335.0 and 334.0 nm, respectively. The surface hydrophobicity slightly
      increased after BC. In a solution of 8 M urea the lambdamax of BSA shifted to
      346.4 and that of BSG to 342.5 nm. In contrast, in the same solution but after BC
      the lambdamax positions of HSA and HSG shifted to 355.9 and 357.7 nm,
      respectively. A decrease in fluorescence intensity, a shift in the maximum of
      emission, and an increase in surface hydrophobicity which reflected unfolding of
      proteins were observed. Here we provide evidence that the loosening of the HSP
      structure takes place primarily in various concentrations of urea before and
      after beer consumption. Differences in the fluorescence behavior of the proteins
      are attributed to disruption of the structure of proteins by denaturants as well
      as by the change in their compactability as a result of ethanol consumption.

PMID- 11307948
TI  - Conformational changes in truncated p47phox proteins monitored by fluorescent
      labeling.
AB  - The leukocyte NADPH oxidase of neutrophils is a membrane-bound enzyme that
      catalyzes the reduction of oxygen to O2- at the expense of NADPH. During
      activation, the cytosolic oxidase components p47phox and p67phox, each containing
      two Src homology 3 (SH3) domains, migrate to the plasma membrane. p47phox and
      p67phox associate with cytochrome b558, a membrane-integrated flavohemoprotein,
      to assemble the active oxidase. Oxidase activation can be mimicked in a cell-free
      system using an anionic amphiphile, such as sodium dodecyl sulfate or arachidonic
      acid, as an activating agent. Activators of the oxidase in vitro cause exposure
      of the SH3 domains of p47phox, which has probably been masked by the C-terminal
      region of this protein in a resting state. We show here that the fluorescence
      exhibited by the covalently labeled N,N'-di-methyl-N(iodoacetyl)-N'-(7-nitrobenz
      2-oxa-1,3-diazol-4-yl) ethyleneamine (IANBD) was increased when N-terminal
      truncated p47Phox-(SH3)2-C was treated with anionic amphiphiles. This finding was
      similar to the results obtained with the full-length p47phox. However, the
      fluorescence of C-terminal-truncated p47Phox-N-(SH3)2 and that of both C-terminal
      and N-terminal truncated p47Phox-(SH3)2 were not altered by the activators. These
      results indicate that the C-terminal region of p47phox is a primary target of the
      conformational change during the activation of NADPH oxidase.

PMID- 11307949
TI  - Expression and properties of recombinant HbA2 (alpha2delta2) and hybrids
      containing delta-beta sequences.
AB  - Hemoglobin A2 (alpha2delta2), which is present at low concentration (1-2%) in the
      circulating red cells of normal individuals, has two important features that
      merit its study, i.e., it inhibits polymerization of sickle HbS and its elevated
      concentration in some thalassemias is a useful clinical diagnostic. However,
      reports on its functional properties regarding O2 binding are conflicting. We
      have attempted to resolve these discrepancies by expressing, for the first time,
      recombinant hemoglobin A2 and systematically studying its functional properties.
      The construct expressing HbA2 contains only alpha and delta genes so that the
      extensive purification required to isolate natural HbA2 is circumvented. Although
      natural hemoglobin A2 is expressed at low levels in vivo, the amount of
      recombinant alpha2delta2 expressed in yeast is similar to that found for adult
      hemoglobin A and for fetal hemoglobin F when the alpha + beta or the alpha +
      gamma genes, respectively, are present on the construct. Recombinant HbA2 is
      stable, i.e., not easily oxidized, and it is a cooperative functional hemoglobin
      with tetramer-dimer dissociation properties like those of adult HbA. However, its
      intrinsic oxygen affinity and response to the allosteric regulators chloride and
      2,3-diphosphoglycerate are lower than the corresponding properties for adult
      hemoglobin. Molecular modeling studies which attempt to understand these
      properties of HbA2 are described.

PMID- 11307950
TI  - A functional raw starch-binding domain of barley alpha-amylase expressed in
      Escherichia coli.
AB  - The mature form of barley seed low-pI alpha-amylase (BAA1) possesses a raw starch
      binding site in addition to the catalytic site. A truncated cDNA encoding the C
      terminal region (aa 281-414) and containing the proposed raw starch-binding
      domain (SBD) but lacking Trp278/Trp279, a previously proposed starch granule
      binding site, was synthesized via PCR and expressed in Escherichia coli as an N
      terminal His-Tag fusion protein. SBD was produced in the form of insoluble
      inclusion bodies that were extracted with urea and successfully refolded into a
      soluble form via dialysis. To determine binding, SBD was purified by affinity
      chromatography with cycloheptaamylose as ligand cross-linked to Sepharose. This
      work demonstrates that a SBD is located in the C-terminal region and retains
      sufficient function in the absence of the N-terminal, catalytic, and Trp278/279
      regions.

PMID- 11307951
TI  - Effect of redox mediators on nitrogenase and hydrogenase activities in
      Azotobacter vinelandii.
AB  - In bioelectrochemical studies, redox mediators such as methylene blue, natural
      red, and thionine are used to studying the redox characteristics of enzymes in
      the living cell. Here we show that nitrogenase activity in Azotobacter vinelandii
      is completely inhibited by oxidized methylene blue (MBo) when the concentration
      of this mediator in the medium is increased up to 72 microM. This activity in A.
      vinelandii is somewhat inhibited by a coenzyme, ascorbic acid (AA). However, the
      nitrogenase activity within the A. vinelandii cell is unchanged even for a high
      concentration of oxidized natural red (NRo) alone. Interestingly, these mediators
      and AA do not have the capacity to inhibit the H2 uptake activity of the
      hydrogenase in A. vinelandii. Average active rates of 66 nM H2 evolved/mg cell
      protein/min from the nitrogenase and 160 nM H2-uptake/mg cell protein/min from
      the hydrogenase in A. vinelandii are found in aid of the activities of the
      enzymes for H2 evolution and for H2 uptake are compared. The activities of both
      enzymes in A. vinelandii are strongly inhibited by thionine having high oxidative
      potential. Mechanisms of various mediators acting in vivo for both enzymes in A.
      vinelandii are discussed.

PMID- 11307952
TI  - Enzymatic characterization of a novel phospholipase A2 from Crotalus durissus
      cascavella rattlesnake (Maracamboia) venom.
AB  - The PLA2 and crotapotin subunits of crotoxin from Crotalus durissus cascavella
      venom were purified by a combination of high-performance liquid chromatography
      (HPLC) molecular exclusion (Protein Pack 300SW column) and reverse-phase HPLC (RP
      HPLC). Tricine SDS-PAGE showed that the PLA2 and crotapotins migrated as single
      bands with estimated molecular masses of 15 and 9 kDa, respectively. The amino
      acid composition of the PLA2 showed the presence of 14 half-cysteines and a high
      content of basic residues (Lys, Arg, His), whereas the crotapotins were rich in
      hydrophobic, negatively charged residues and half-cysteines. The PLA2 showed
      allosteric behavior, with maximal activity at pH 8.3 and 35-40 degrees C. C. d.
      cascavella PLA2 required Ca2+ for activity but was inhibited by Cu2+ and Zn2+ and
      by Cu2+ and Mg2+ in the presence and absence of Ca2+, respectively. Crotapotin
      (F3) and heparin inhibited the catalytic activity of the PLA2 by acting as
      allosteric inhibitors.

PMID- 11307953
TI  - The proteolytic activity of the recombinant cryptic human fibronectin type IV
      collagenase from E. coli expression.
AB  - Human plasma fibronectin (pFN) contains a cryptic metalloprotease present in the
      collagen-binding domain. The enzyme could be generated and activated in the
      presence of Ca2+ from the purified 70-kDa pFN fragment produced by cathepsin D
      digestion. In this work we cloned and expressed the metalloprotease, designated
      FN type IV collagenase (FnColA), and a truncated variant (FnColB) in E. coli. The
      recombinant pFN protein fragment was isolated from inclusion bodies, and
      subjected to folding and autocatalytic degradation in the presence of Ca2+, and
      yielded an active enzyme capable of digesting gelatin, helical type II and type
      IV collagen, alpha- and beta-casein, insulin b-chain, and a synthetic Mca
      peptide. In contrast, isolated plasma fibronectin, type I collagen, and the DNP
      peptide were no substrates. Both catalytically active recombinant pFN fragments
      were efficiently inhibited by EDTA, and batimastat, and, in contrast to the
      glycosylated enzyme isolated from plasma fibronectin, were also inhibited by TIMP
      2.

PMID- 11307954
TI  - Purification, characterization, and relation to bikunin of rat urinary trypsin
      inhibitors.
AB  - Two forms of urinary trypsin inhibitor (UTI-1 and UTI-2) were purified from
      pooled urine of normal male rats to apparent homogeneity by salting out, affinity
      chromatography, gel filtration, and reverse-phase HPLC. UTIs-1 and 2 were shown
      to be thermostable glycoproteins with the respective molecular weights of 22,000
      and 18,000 estimated by SDS-PAGE. These inhibitors combined with bovine trypsin
      in a 1:1 molar ratio: the Kd values were 2.5 x 10(-10) and 2.3 x 10(-10) M,
      respectively. Amino acid composition and sequence analysis indicated that UTI-1
      corresponded to rat bikunin of which the amino acid sequence was deduced from a
      rat liver cDNA clone encoding alpha1-microglobulin [Lindqvist et al. (1992),
      Biochim. Biophys. Acta 1130, 63-67] except that the protein sequence seemed to
      lack C-terminal serine, and UTI-2 corresponded to UTI-1 lacking N-terminal 21
      amino acid residues.

PMID- 11307955
TI  - Recombinant derivatives of clostridial neurotoxins as delivery vehicles for
      proteins and small organic molecules.
AB  - Clostridial neurotoxins are the most powerful toxins known. Nevertheless,
      derivatives of these toxins may find broad applications both in science and
      medicine because of their unique abilities to recognize neurons and deliver small
      and large molecules into them. In this paper we describe the construction of two
      types of such derivatives. Proteins belonging to the first class were designed to
      allow direct conjugation with one or few molecules of interest. Proteins
      belonging to the second class contain biotin residue and therefore could be
      easily connected to streptavidin loaded with multiple molecules of interest. Only
      C-terminal regions of neurotoxin heavy chains were incorporated in the structure
      of recombinant proteins. Nevertheless, recombinant proteins were found to be able
      to recognize specific neuronal receptors and target model molecules to rat
      synaptosomes and human neuroblastoma cells.

PMID- 11307956
TI  - Purification and catalytic properties of two catechol 1,2-dioxygenase isozymes
      from benzoate-grown cells of Acinetobacter radioresistens.
AB  - Two catechol 1,2-dioxygenase (C1,2O) isozymes (IsoA and IsoB) have been purified
      to homogeneity from a strain of Acinetobacter radioresistens grown on benzoate as
      the sole carbon and energy source. IsoA and IsoB are both homodimers composed of
      a single type of subunit with molecular mass of 38,600 and 37,700, Da
      respectively. In conditions of low ionic strength, IsoA can aggregate as a
      trimer, in contrast to IsoB, which maintains the dimeric structure, as also
      supported by the kinetic parameters (Hill numbers). IsoA is identical to the
      enzyme previously purified from the same bacterium grown on phenol, whereas the
      IsoB is selectively expressed using benzoate as carbon source. This is the first
      evidence of the presence of differently expressed C1,2O isozymes in A.
      radioresistens or more generally of multiple C1,2O isozymes in benzoate-grown
      Acinetobacter cells. Purified IsoA and IsoB contain approximately 1 iron(III) ion
      per subunit and both show electronic absorbance and EPR features typical of
      Fe(III) intradiol dioxygenases. The kinetic properties of the two enzymes such as
      the specificities toward substituted catechols, the main catalytic parameters,
      and their behavior in the presence of different kind of inhibitors are,
      unexpectedly, very similar, in contrast to most of the previously known
      dioxygenase isozymes.

PMID- 11307957
TI  - Congenital adrenal hyperplasia: from genetics and biochemistry to clinical
      practice, part 2.
AB  - Congenital adrenal hyperplasia (CAH) refers to a group of genetic disorders with
      defects in the synthesis of cortisol. The synthesis of other steroids such as
      mineralocorticoids and adrenal/ gonadal sex steroids may also be affected. The
      clinical presentation of the various forms of CAH depend on the following: (1)
      the affected enzyme, (2) the residual enzymatic activity, (3) the physiologic
      consequences of deficiencies of the end-products and excess of precursors. The
      second part of this two-part review discusses the diagnosis and the management of
      CAH. Although methods for the diagnosis of CAH have not changed over the past few
      years, new therapeutic approaches are changing the management of CAH. In
      particular, new drugs and new drug combinations are being tested and old dogmas
      are being questioned. Early diagnosis, careful discussion with family members of
      newborns with CAH during the early decision-making process, and close management
      will decrease the mortality rate and improve the long-term psychological/physical
      outcome of these children.

PMID- 11307958
TI  - Adolescents with ASCUS: are they a high risk group?
AB  - Population demographics, risk behaviors, and compliance rates for the management
      of an ASCUS (atypical squamous cells of undetermined significance) diagnosis are
      not well studied in the adolescent population. From June 1994 to December 1996,
      1,175 Papanicalou (pap) smears were performed in an urban adolescent clinic on
      patients age 12 to 18. Of these, 124 (10.5%) were diagnosed with ASCUS or ASCUS
      with a qualifying statement. A retrospective chart review (n=83) and telephone
      interview was performed on patients with ASCUS. Ninety-nine percent of enrollees
      were African American. Comparisons were made between those patients with normal
      pap smears and those with ASCUS. No statistically significant difference existed
      pertaining to age at pap smear, age at menarche, age at first coitus, and
      education level. A positive association was found in the ASCUS group for the
      presence of sexually transmitted diseases (P < 0.001), number of sexual partners
      (P < 0.0007), and pregnancy (P < 0.001). Of the 80% of patients who had an ASCUS
      diagnosis and were referred for colposcopy (n = 62), only 61% attended their
      appointment (n = 38). Thirty-nine percent of these patients were aware of an
      abnormal diagnosis after colposcopy. For those that attended colposcopy, 56% were
      accompanied by a parent. For those who were not compliant with attendance, none
      cited parental consent for the procedure as a barrier to obtaining treatment.
      Adolescent females in an urban setting with multiple sexual partners, history of
      sexually transmitted diseases, and prior pregnancy are at a greater risk for
      ASCUS on cervicovaginal smear when compared to their age-matched controls. In
      addition, the adolescent compliance rate for colposcopy is low. We, therefore,
      recommend that these adolescent females be observed diligently.

PMID- 11307959
TI  - The utility of skin biopsies in pediatric cancer patients: a single-institution,
      retrospective review.
AB  - Medical records of all patients who were diagnosed with a malignancy and who
      underwent a skin biopsy were reviewed to determine the clinical utility of skin
      biopsies in this population. Skill biopsies resulted in a change or refinement of
      the prebiopsy diagnosis in 44% of patients undergoing an initial evaluation for a
      malignancy, 57% of patients on therapy, and 17% of patients off therapy. Skin
      biopsies led to a change in therapy in 26%, 34%, and 17% of each respective
      group. Overall, the skin biopsy changed or refined the prebiopsy diagnosis in 45%
      of cases and altered therapy in 38%. Skin biopsy is a clinically useful tool in
      pediatric oncology patients for the evaluation of cutaneous findings that elude
      diagnosis by visual inspection.

PMID- 11307960
TI  - Serum homocysteine and lipoprotein (a) concentrations in hypercholesterolemic and
      normocholesterolemic children.
AB  - The relationship between lipids, lipoproteins, total homocysteine, and
      lipoprotein (a) was studied in hypercholesterolemic and normocholesterolemic
      children. In hypercholesterolemic children, concentrations of total cholesterol,
      low-density lipoprotein (LDL) cholesterol, apolipoprotein B, and triglycerides
      were significantly higher compared to levels in controls, whereas concentrations
      of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were lower
      compared to those in the control group. Total serum homocysteine concentrations
      in children with a positive family history for cardiovascular disease CHD(+)
      (7.28 micromol/L) were significantly higher than those in the control group (5.45
      micromol/L), and in the group of CHD(-) children (5.25 micromol/L). The median
      value of lipoprotein (a) in patients was 31.5 mg/dL (range, 11-209 mg/dL) and in
      the control group, 19 mg/dL (range, 11-95 mg/dL). Concentrations of Lp (a),
      exceeding 30 mg/dL, were present in 45% of CHD(+) children, in 29% of CHD(-)
      children, and in only 11% of the control group.

PMID- 11307961
TI  - A 10-week old infant with meningitis.

PMID- 11307962
TI  - Pasteurella multocida pneumonia in an adolescent with Duchenne's muscular
      dystrophy following exposure to his helper dog.

PMID- 11307963
TI  - Precocious puberty resulting from congenital hypothalamic hamartoma: persistent
      darkened areolae after birth as the hallmark of estrogen excess.

PMID- 11307964
TI  - A health passport for adolescent parents and their children.

PMID- 11307965
TI  - PPD-tuberculin skin testing and TB prophylaxis of children, The Bronx, New York.

PMID- 11307966
TI  - Corynebacterium xerosis sepsis in a pediatric patient with sickle cell disease (a
      case report).

PMID- 11307967
TI  - A rare cause of obstructive respiratory distress in the newborn: congenital
      nasopharyngeal teratoma.

PMID- 11307968
TI  - NADH-dependent reduction of sulphamethoxazole hydroxylamine in dog and human
      liver microsomes.
AB  - 1. Reduction of hydroxylamine drug metabolites by NADH-dependent hydroxylamine
      reductase (NDHR) has been suggested to be involved in the pathogenesis of
      idiosyncratic sulphonamide toxicity in humans. The dog represents a naturally
      occurring clinical model for sulphonamide toxicity in humans. he purpose of these
      studies, therefore, was to characterize the presence of hepatic NADH-dependent
      hydroxylamine reductase activity in the dog and to compare this activity with
      that found in humans. 2. NDHR activity was characterized by the presence of two
      enzymes in both dog and human liver microsomes, with comparable estimates of Km
      (Km1 = 75 microM, Km2 = 404 microM in dog; Km1 = 69 microM, Km2 = 503 microM in
      human). Estimates of maximal velocity were significantly, but not dramatically,
      higher for dog NDHR (Vmax1 = 2.09 nmole mg(-1) min(-1) Vmax2 = 4.58 nmole mg(-1)
      min(-1) compared with human NDHR (Vmax1 = 0.42 nmole mg(-1) min(-1), Vmax2 = 1.56
      nmole mg(-1) min(-1)). NDHR in dog, as in humans, preferred NADH to NADPH, was
      more active at pH 6.3 than at 7.4 and was not inhibited by carbon monoxide,
      azide, anaerobic conditions, the CYP substrate inhibitors tolbutamide,
      dextromethorphan, or erythromycin, or antibodies directed against CYP2C, CYP2D or
      CYP3A. 3. It is concluded that two forms of NDHR are present in dog and humans
      with similar biochemical characteristics. Although NDHR activity has been
      attributed to a CYP2D isoform in pig, there is no evidence for involvement of
      CYP450 in the reduction of sulphamethoxazole hydroxylamine in either dogs or
      humans.

PMID- 11307969
TI  - Effects of flupyrazofos on liver microsomal cytochrome P450 in the male Fischer
      344 rat.
AB  - 1. The effects of flupyrazofos on liver microsomal cytochrome P450 were
      investigated in the male Fischer 344 rat. When rats were treated
      intraperitoneally with flupyrazofos for 3 consecutive days, the activities of
      ethoxyresorufin O-deethylase and testosterone 2 beta-hydroxylase were
      significantly reduced, whereas the activities of pentoxyresorufin beta
      depentylase and testosterone 6beta- and 7 alpha-hydroxylases were induced in
      liver microsomes. 2. Within 24 h after treatment with 50 m kg(-1) flupyrazofos,
      most enzyme activities were decreased, indicating the interaction of flupyrazofos
      with cytochrome P450. 3. In Western immunoblotting, cytochrome P4502B1/2 proteins
      were clearly induced by treatment with flupyrazofos, whereas P4501A1/2 and 2C6
      proteins were reduced in liver microsomes. 4. The present results indicate that
      flupyrazofos modulates the expression of cytochrome P450 in rat.

PMID- 11307970
TI  - Determining the best animal model for human cytochrome P450 activities: a
      comparison of mouse, rat, rabbit, dog, micropig, monkey and man.
AB  - 1. In the present study, nine cytochrome P450 enzyme activities in seven species
      were characterized to allow a practical means of comparing this important
      metabolic step between various test animals and man. 2. Enzyme activities and
      kinetic parameters were first determined towards marker substrates for human
      cytochrome P450 enzymes. Inhibition profiles were then determined with both
      antibodies directed against various cytochrome P450 enzymes and with chemical
      inhibitors. 3. Both the enzyme kinetic parameters/enzyme activities, and the
      inhibition profiles obtained for the animal species were compared with those
      obtained for human liver microsomes in order to postulate the animal species most
      similar to man with regard to each individual cytochrome P450 enzyme activity. 4.
      It was found that, as expected, none of the tested species was similar to man for
      all the measured P450 enzyme activities, but that in each species only some of
      the P450 enzyme activities could be considered as similar to man. 5. When it is
      known which human cytochrome P450 enzymes are involved in the metabolism of a
      compound, the comparative data presented here can be used for selecting the most
      suitable species for in vitro and in it no experiments.

PMID- 11307971
TI  - Metabolism of N-isopropylacetanilide in rat.
AB  - 1. Radioactivity from oral doses of N-isopropyl[1-14C]acetanilide was excreted in
      urine (53.5%), faeces (8.1%) and expired air (17.0%) of rat. 2. Enterohepatic
      circulation occurred during formation of approximately 34% of the metabolites. N
      isopropylacetanilide was metabolized by oxidation in all moieties of the molecule
      with subsequent conjugation with glucuronic and sulphuric acids. 3. The sulphate
      ester of 4'-hydroxyacetanilide (acetaminophen) was the major metabolite (28 % of
      the dose).

PMID- 11307972
TI  - Role of helix formation for the retention of peptides in reversed-phase high
      performance liquid chromatography.
AB  - In order to get insight into the role of helix formation for retention in
      reversed-phase HPLC, we have studied the isocratic retention behavior of
      amphipathic and non-amphipathic potentially helical model peptides. Plots of the
      logarithmic capacity factor in absence of organic solvent (ln k0) versus l/T were
      used to derive the enthalpy, deltaH0, the free energy, deltaG0, the entropy of
      interaction, deltaS0, and the heat capacity change, deltaCp. Retention of all
      peptides was accompanied by negative deltaCp revealing that hydrophobic
      interactions play a large role independent of peptide sequence and secondary
      structure. deltaH0 was negative for the amphipathic analogs and was attributed
      mainly to helix formation of these peptides upon interaction with the stationary
      phase. In contrast, deltaH0 was considerably less exothermic or even endothermic
      for the non-amphipathic analogs. The differences in helix formation between the
      individual analogs were quantified on the basis of thermodynamic data of helix
      formation previously derived for peptides in a hydrophobic environment.
      Correlation of the helicity with the free energy of stationary phase interaction
      revealed that helix formation accounts for approximately 40-70% of deltaG0, and
      is hence in addition to the hydrophobic effect a major driving force of
      retention.

PMID- 11307973
TI  - Selectivity assessment of popular stationary phases for open-tubular column gas
      chromatography.
AB  - The solvation parameter model is used to study the influence of temperature and
      composition on the selectivity of nine poly(siloxane) and two poly(ethylene
      glycol) stationary phase chemistries for open-tubular column gas chromatography.
      A database of system constants for the temperature range 60-140 degrees C was
      constructed from literature values with additional results determined for HP-50+,
      DB-210, DB-1701, DB-225 and SP-2340 columns. The general contribution of monomer
      composition (methyl, phenyl, cyanopropyl, and trifluoropropyl substituents) on
      the capacity of poly(siloxane) stationary phases for dispersion, electron lone
      pair, dipole-type and hydrogen-bond interactions is described. The selectivity
      coverage of the open-tubular column stationary phases is compared with a larger
      database for packed column stationary phases at a reference temperature of 120
      degrees C. The open-tubular column stationary phases provide reasonable coverage
      of the range of dipole-type and hydrogen-bond base interactions for non-ionic
      packed column stationary phases. Deficiencies are noted in the coverage of
      electron lone pair interactions. None of the open-tubular column stationary
      phases are hydrogen-bond acids. The system constants are shown to change
      approximately linearly with temperature over the range 60-140 degrees C. The
      intercepts and slopes of these plots are used to discuss the influence of
      temperature on stationary phase selectivity.

PMID- 11307974
TI  - Sensitive determination of bisphenol A in environmental water by gas
      chromatography with nitrogen-phosphorus detection after cyanomethylation.
AB  - A new technique is proposed for the determination of bisphenol A in environmental
      water. The sample preparation consists of a single-step extraction of bisphenol A
      from a water sample with methylene chloride and the cyanomethyl derivatization of
      bisphenol A. 2,2'-Biphenol is used as an internal standard. Bisphenol A and
      biphenol can be quantitatively converted to their corresponding cyanomethyl
      ethers, which are then measured by gas chromatography with nitrogen-phosphorus
      detection. Peak shape and quantification of bisphenol A are excellent, with
      linear calibration curves over a range of 0.1-100 ng/ml. The detection limit is
      0.1 ng/ml in water samples. The average recovery and RSD at a concentration of 5
      ng/ml are 89.3 and 4.5%, respectively. The procedure is applicable to the
      quantification of bisphenol A in tap water, raw water and stream water.

PMID- 11307975
TI  - Monitoring of isothiocyanates emanating from Arabidopsis thaliana upon paraquat
      spraying.
AB  - Arabidopsis thaliana plants were sprayed with the superoxide-generating herbicide
      paraquat. The headspace of sprayed plants was characterized by a number of
      compounds, which were absent in the headspace of untreated plants. They were
      identified as isothiocyanates (ITCs) with 4-methylthiobutyl isothiocyanate as
      main compound. After identification, a GC-system, based on PDMS sorption, was
      used to continuously monitor the ITC emissions. The specificity of isothiocyanate
      emission was also determined by subjecting the Arabidopsis thaliana plants to in
      vitro mechanical wounding. Again, 4-methylthiobutyl isothiocyanate was the main
      component, but the emission profile was completely different since the compound
      was emitted immediately, i.e., during wounding itself.

PMID- 11307976
TI  - On the equations describing chromatographic peaks and the problem of the
      deconvolution of overlapped peaks.
AB  - The problem of the appropriate choice of the function that describes a
      chromatographic peak is examined in combination with the deconvolution of
      overlapped peaks by means of the non-linear least-squares method. It is shown
      that the majority of the functions proposed in the literature to describe
      chromatographic peaks are not suitable for this purpose. Only the polynomial
      modified Gaussian function can describe almost every peak but it is
      mathematically incorrect unless it is redefined properly. Two new functions are
      proposed and discussed. It is also shown that the deconvolution of an overlapping
      peak can be done with high accuracy using a non-linear least-squares procedure,
      like Microsoft Solver, but this target is attained only if we use as fitted
      parameters the position of the peak maximum and the peak area (or height) of
      every component in the unresolved chromatographic peak. In case we use as fitted
      parameters all the parameters that describe each single peak enclosed in the
      multi-component peak, then Solver leads to better fits, which though do not
      correspond to the best deconvolution of the peak. Finally, it is found that
      Solver gives much better results than those of modern methods, like the immune
      and genetic algorithms.

PMID- 11307977
TI  - Low-temperature clean-up method for the determination of organophosphorus
      insecticides in olive oil.
AB  - A simple, extremely low-cost method using low-temperature lipid precipitation has
      been developed for the rapid analysis of virgin olive oil for organophosphorus
      insecticides and triazine herbicides commonly used in olive groves. The method
      gives good clean-up for GC analysis with nitrogen-phosphorus detection and
      recoveries between 77 and 104%, with RSD values of 7-16%. Matrix enhancement was
      observed for some pesticides and metabolites.

PMID- 11307978
TI  - Application of micro-scale sealed vessel thermal desorption-gas chromatography
      mass spectrometry for the organic analysis of airborne particulate matter:
      linearity, reproducibility and quantification.
AB  - Micro-scale sealed vessel thermal desorption-gas chromatography-mass spectrometry
      (MSSV-TD-GC-MS) has been applied to the analysis of airborne particulate matter
      using the US NIST Standard Reference Material (SRM1649a) urban dust. We make
      qualitative comparisons with open system desorption and illustrate that caution
      should be used when using the technique without an open system comparison. We
      report linear responses over the same particulate mass range (1-5 mg) and good
      reproducibility [SD< or =0.62 mg kg(-1) (< or = 11%)]. We show linearity for a
      series of 10 n-alkanes and 10 polycyclic aromatic hydrocarbons (PAHs) in the SRM.
      The technique is also shown to be quantifiable (PAH concentrations typically 4-6
      mg kg(-1)).

PMID- 11307979
TI  - New method for rapid solid-phase extraction of large-volume water samples and its
      application to non-target screening of North Sea water for organic contaminants
      by gas chromatography-mass spectrometry.
AB  - A method has been developed that allows the solid-phase extraction of
      microorganic compounds from large volumes of water (10 l) for non-target analysis
      of filtered seawater. The filtration-extraction system is operated with glass
      fibre filter candles and the polymeric styrene-divinylbenzene sorbent SDB-1 at
      flow-rates as high as 500 ml/min. Recovery studies carried out for a couple of
      model substances covering a wide range of polarity and chemical classes revealed
      a good performance of the method. Especially for polar compounds (log Kow 3.3
      0.7) quantitative recovery was achieved. Limits of detection were between 0.1 and
      0.7 ng/l in the full scan mode of the MS. The suitability of the method for the
      analysis of marine water samples is demonstrated by the non-target screening of
      water from the German Bight for the presence of organic contaminants. In the
      course of this screening a large variety of substances was identified including
      pesticides, industrial chemicals and pharmaceuticals. For some of the identified
      compounds their occurrence in marine ecosystems has not been reported before,
      such as dichloropyridines, carbamazepine, propyphenazone and caffeine.

PMID- 11307980
TI  - On-line flow sample stacking in a flow injection analysis-capillary
      electrophoresis system: 2000-fold enhancement of detection sensitivity for
      priority phenol pollutants.
AB  - A flow injection analysis-capillary electrophoresis system has been used for on
      line flow stacking of 11 US Environmental Protection Agency priority phenol
      pollutants. Samples containing low concentrations of phenols dissolved in
      deionised water are continuously delivered to the capillary opening by means of a
      peristaltic pump. The sample components stack at the boundary between the highly
      conductive separation electrolyte and the introduced sample. By selecting an
      appropriate electrolyte and stacking conditions the movement of the electrolyte
      solution inside the capillary can be reduced, thereby improving the stacking
      efficiency. The electrolyte used here contained 20 mM phosphate, 8% 2-butanol,
      and 0.001% hexamethonium bromide at pH 11.95, and the stacking was carried out at
      2 kV for 240 s. These conditions allowed up to 2000-fold preconcentration of the
      selected phenols. No matrix removal was necessary.

PMID- 11307981
TI  - High-performance chiral separation of fourteen triazole fungicides by sulfated
      beta-cyclodextrin-mediated capillary electrophoresis.
AB  - In this paper, sulfated beta-cyclodextrin-mediated capillary electrophoresis (CE)
      is evaluated as a new approach for the chiral separation of triazole-type
      fungicides. The 14 fungicides investigated were bitertanol, cyproconazole,
      difenoconazole, diniconazole, flutriafol, hexaconazole, myclobutanil,
      paclobutrazol, penconazole, propiconazole, tebuconazole, tetraconazole,
      triadimefon and triadimenol. Under the optimal conditions, excellent
      enantioseparation was achieved for all the 14 fungicides, including those
      fungicides containing two chiral centers. To our knowledge, this is the only
      system to date that offers outstanding enantiodiscrimination towards all triazole
      type fungicides. The impact of the molecular structures of the triazole compounds
      on their migration behavior was studied. Similar to other chemical systems
      involving host-guest complexation, the interaction between sulfated beta
      cyclodextrin and the triazole compounds was found to be affected by a variety of
      factors, including electrostatic force, hydrogen bonding, steric effect and
      hydrophobicity. These factors, coupled with the countercurrent electroosmotic
      flow (EOF), were believed to be the major forces behind the exceptional chiral
      selectivity.

PMID- 11307982
TI  - Preparative isolation and purification of acteoside and 2'-acetyl acteoside from
      Cistanches salsa (C.A. Mey.) G. Beck by high-speed counter-current
      chromatography.
AB  - High-speed counter-current chromatography (HSCCC) was applied to the separation
      and purification of phenylethanoid glycosides (PhGs) acteoside and 2'
      acetylacteoside from Cistanches salsa (C.A. Mey) G. Beck with a quaternary two
      phase solvent system composed of ethyl acetate-n-butanol-ethanol-water
      (4:0.6:0.6:5, v/v). HPLC analyses of the CCC fractions revealed that the two main
      PhGs were over 98% purity. Their chemical structures were identified by 1H NMR,
      13C NMR and MS.

PMID- 11307983
TI  - Analysis of triacylglycerol positional isomers in food products as brominated
      derivatives by high-performance liquid chromatography coupled with a flame
      ionization detection.
AB  - Reversed-phase HPLC resolution and HPLC-flame ionization detection quantitation
      of model triacylglycerol positional isomer pairs (important in the study of food
      formulation lipids) after facile conversion to brominated derivatives is
      reported. The positional isomers in the triacylglycerol pairs were at least 98%
      resolved from each other during reversed-phase HPLC. Triacylglycerol quantitation
      obtained by HPLC-flame ionization detector was checked against standard
      positional isomer pairs known by mass. The flame ionization detection area
      percent gave absolute error range of 0.3-1.6% per triacylglycerol.

PMID- 11307984
TI  - Poly(glycidyl methacrylate-divinylbenzene-triallylisocyanurate) continuous-bed
      protein chromatography.
AB  - A novel continuous bed with high dynamic adsorption capacity for protein has been
      developed. It is a macroporous poly(glycidyl methacrylate-divinylbenzene
      triallylisocyanurate) rod prepared by in situ copolymerization in a
      chromatographic tube. The bed matrix contained epoxy groups, so
      diethylaminohydroxypropyl groups were coupled to the matrix, leading to an anion
      exchange continuous bed. The component, specific surface area, and the pore
      structure of the bed matrix were characterized by Fourier transform infrared
      spectroscopy, BET method and scanning and transmission electron microscopies,
      respectively. The flow properties, column efficiency and the dynamic adsorption
      behavior of the bed were studied. The results show that the continuous bed, a
      ternary copolymer of glycidyl methacrylate (GMA), divinylbenzene (DVB) and
      triallylisocyanurate (TAIC) with a specific surface area of 56.4 m2/g, consisted
      of a three-dimensional structure made up of continuous clusters of microspheres
      (300 nm) and interconnected irregular pores. The rate of mass transfer is
      enhanced by the convection of the mobile phase through the pores. The dynamic
      adsorption isotherm of the anion-exchange column for bovine serum albumin was
      expressed by the Langmuir equation with a dynamic capacity as high as 76.0 mg/g.
      Moreover, the separation of proteins, i.e. lysozyme, hemoglobin and bovine serum
      albumin, is little affected by mobile-phase velocity up to 902.5 cm/h; it was
      completed within 5 min at 902.5 cm/h.

PMID- 11307985
TI  - Microdialysis of salicylic acid from viscous emulsion samples prior to high
      performance liquid chromatographic determination.
AB  - A micro-dialysis method was developed to isolate aqueous salicylic acid from
      viscous emulsion samples prior to HPLC determination. The optimal conditions for
      obtaining dialysis efficiency of salicylic acid as well as chromatographic
      conditions were investigated. Experimental results indicated that the dialysis
      achieved at pH 2.0 (0.025 M phosphate solution), 0.5 M NaCl addition, and 50
      microl/min flow-rate of perfusion stream offered an optimal result. The proposed
      method provided a simple procedure for isolating salicylic acid from viscous
      emulsion samples. Application was illustrated by the analysis of salicylic acid
      in cosmetic products.

PMID- 11307986
TI  - Separation of steroids using temperature-dependent inclusion chromatography.
AB  - The influence of temperature on retention and separation of estrogens,
      progesterone derivatives and beta-cyclodextrin in reversed-phase high-performance
      liquid chromatography has been studied. Steroids were detected using direct UV
      detection at 240 and 280 nm. Detection of beta-cyclodextrin was achieved using a
      post-column indirect photometric method. Chromatographic experiments were
      performed using an acetonitrile-water mobile phase (30%, v/v) and a wide range of
      column temperatures from 0 to 80 degrees C with 20 degrees C steps. Linear Van't
      Hoff plots were observed for steroids and beta-cyclodextrin when an unmodified
      binary mobile phase was applied. The retention of steroids was strongly
      influenced by temperature when the mobile phase was modified with beta
      cyclodextrin at a concentration of 12 mM. Particularly, for 17beta-estradiol and
      20alpha-hydroxyprogesterone a strong deviation from the linear Van't Hoff plots
      and a remarkable affinity for beta-cyclodextrin was observed. Polynomial
      regression calculations were performed to fit the set of experimental data
      points. Using third-order polynomial equations, minimum separation factor values
      (alphamin) were calculated for temperatures from -10 to + 100 degrees C with 1
      degrees C steps. The best chromatographic conditions for separation of
      multicomponent samples were chosen. A possible retention mechanism for solutes in
      the presence of macrocyclic additives is discussed. The results presented
      describe the role of temperature in high-performance liquid chromatography
      systems in which the mobile phase is modified with an inclusion agent.

PMID- 11307987
TI  - Analysis of sulfonated compounds by ion-exchange high-performance liquid
      chromatography-mass spectrometry.
AB  - Ion-exchange high-performance liquid chromatography (HPIEC)-mass spectrometry
      (MS) was used for the analysis of different sulfonated compounds. HPIEC was
      performed on an aminopropyl column applying a gradient with increasing
      concentration of a buffer consisting of ammonium acetate-acetic acid and
      acetonitrile as the organic modifier. HPIEC is well suited to highly efficient
      separation of sulfonated compounds and furthermore, due to the volatility of
      ammonium acetate, the method is also appropriate for LC-MS coupling by the means
      of either atmospheric pressure chemical ionization or electrospray ionization.
      The applicability range of HPIEC-MS is demonstrated on the basis of a complex
      mixture of model substances consisting of sulfonated aromatics and textile dyes
      largely differing from each other in their structural properties.

PMID- 11307988
TI  - Supercritical fluid extraction for liquid chromatographic determination of
      carotenoids in Spirulina Pacifica algae: a chemometric approach.
AB  - An experimental design procedure was used to investigate the effects of some
      operating parameters on the supercritical fluid extraction of carotenoids beta
      carotene, beta-cryptoxanthin and zeaxanthin from Spirulina Pacifica algae, a
      carotenoid-rich dietary product. Variables tested were temperature and pressure
      of the supercritical fluid, dynamic extraction time and percentage of ethanol
      added as the modifier. Each variable was tested at three levels; 31 experiments
      were performed in random order. Analyses of the extracts were performed by high
      performance liquid chromatography with UV-Vis photodiode array detection.
      Analytical responses (chromatographic peak areas) were processed by using a
      stepwise multiple regression analysis, in order to find polynomial functions
      describing the relationships between variables and responses. For all the
      analytes the experimental conditions providing the highest extraction yield
      inside the experimental domain considered were found. Supercritical fluid
      extraction results obtained in these conditions were compared with those obtained
      by performing solvent extraction in order to evaluate the effectiveness of the
      supercritical fluid extraction procedure.

PMID- 11307989
TI  - Evaluation and comparison of two improved techniques for the on-line detection of
      antioxidants in liquid chromatography eluates.
AB  - Two methods for the on-line detection in HPLC eluates of analytes possessing
      radical scavenging activity were improved and compared. The instrumental set-up
      of the method that is based on on-line inhibition of luminol chemiluminescence
      (CL) by antioxidants was improved using better quality syringe pumps, employing a
      diode array detector, and introducing a mixing/neutralisation coil and a pulse
      damper. Sensitivity of the HPLC-CL detection increased by a factor of 4. Post
      column neutralisation of eluates improved compatibility of this detection method
      with acidified HPLC eluents. The second method, which is based on the post-column
      quenching of 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH*), was improved by
      readjusting composition and flow-rate of the reagent, mounting an additional
      pulse damper and detecting unreacted DPPH* with a detector equipped with a
      tungsten lamp. Purging of the DPPH* solution with He gas prior to analysis was
      introduced. This led to 30-fold better detection limits. The improved methods
      were compared with respect to limits of detection, the radical scavenging
      mechanism involved, compatibility with common HPLC solvents and pH range, and
      some technical aspects. The techniques described have high potential for the
      rapid identification of radical scavengers in complex samples like plant
      extracts.

PMID- 11307991
TI  - Identification of unknown degradation products in a new cholesterol-reducing drug
      by ion-chromatography coupled to mass spectrometry.
AB  - The combination of suppressed and non-suppressed cation-exchange chromatography
      with electrospray ionization mass spectrometry was demonstrated for the
      structural elucidation of unknown by-products (mostly quaternary ammonium
      compounds) in a new cholesterol-reducing drug. The suppressed mode using
      methanesulfonic acid and acetonitrile turned out to be unsuitable because of
      regenerant (tetrabutylammonium hydroxide) passing through the membrane of the
      suppressor into the eluent which led to a significant increase of spectral
      background in the mass spectrometer. Employing a mobile phase consisting of 200
      mM formic acid and 60% (v/v) acetonitrile, the separation and detection of 8
      unknown compounds was possible in the non-suppressed mode. The three most
      prominent compounds were selected for structural elucidation utilizing collision
      induced dissociation experiments. In a series of experiments the fragmentation
      behavior was investigated for different fragmentation voltages finally leading to
      structure proposals. Using gas chromatography hyphenated with mass spectrometry,
      additional information for the structure of the unknowns was collected and a
      possible way of their formation was proposed.

PMID- 11307990
TI  - Selective enrichment of 17 pyrethroids from lyophilised agricultural samples.
AB  - The screening of agricultural samples to determine 17 synthetic pyrethroids was
      investigated. Samples were lyophilised without losses of the insecticides, and
      then extracted with n-hexane. A simple, continuous preconcentration-elution
      system was developed, which included a silica sorbent column (packed with 50 mg)
      and used an air stream to carry the eluent (ethyl acetate) which minimised the
      eluate volume thus increasing the preconcentration factor; so no evaporation step
      was required. Pyrethroids were determined by gas chromatography-electron capture
      detection (GC-ECD) by using a 5% phenylmethylpolysiloxane-coated fused-silica
      capillary column; gas chromatography-mass spectrometry was used to identify the
      pyrethroids detected by GC-ECD monitoring. Limits of detection varied between 0.1
      and 0.8 ng/ml (except for piperonyl butoxide, 25 ng/ml) with linear ranges from 1
      to 200 ng/ml; the precision of the method was high (3-6%). Recoveries of 17
      insecticides from 14 different agricultural samples fortified at levels of 20-100
      ng/g ranged from 66 to 102% (bifenthrin and deltamethrin were those providing the
      lowest values, 66-87%). Pyrethroids were detected in eight samples (from the 100
      unfortified agricultural samples tested) at concentrations lower than the
      established maximum residue limits (MRLs).

PMID- 11307992
TI  - New halogen-specific detector applied to the analysis of chlorinated fatty acids.
AB  - A new halogen-specific detection method (XSD) was tested for determination of
      chlorinated fatty acids in marine biota. In XSD, an increased emission of ions
      and electrons is caused by the high-temperature combustion of halogen-containing
      compounds. The detection limit of methyl dichlorooctadecanoate and the
      selectivity at a reactor temperature of 900 degrees C match those of electrolytic
      conductivity detection (ELCD). The relative standard deviation is less than 11%
      for > or =0.2 ng methyl dichlorooctadecanoate. An XSD chromatogram of a complex
      sample, chlorinated fatty acid methyl esters liberated from fish lipids, agreed
      with a previously obtained ELCD chromatogram.

PMID- 11307993
TI  - Open versus percutaneous dilatational tracheostomy: efficacy and cost analysis.
AB  - The economic advantages of percutaneous dilatational tracheostomies versus open
      tracheostomies in the operating room have been thoroughly evaluated. We are now
      reporting our comparison of the costs and charges of percutaneous dilatational
      tracheostomies with those of open bedside tracheostomies at our institution. The
      current literature comparing the two open techniques and the percutaneous method
      of placing tracheostomies was reviewed and the charges and costs for these
      procedures at our institution were compared. Patients were placed into one of
      three groups for analysis: open tracheostomies in the operating room (Group I),
      open tracheostomies in the intensive care unit (Group II), and percutaneous
      dilatational tracheostomies in the intensive care unit (Group III). Based on our
      own experience and a literature review it is evident that all three approaches to
      tracheostomies are safe. Economic analysis showed a savings of $180 in cost per
      procedure and a $658 savings in charges per procedure for the open method at the
      bedside when compared with the percutaneous method at the bedside. The
      professional fee for bronchoscopy was not included in this calculation; including
      this would lead to greater savings with the open method over the percutaneous
      method. Open tracheostomy in the operating room increased costs over the bedside
      procedure by $2194 and increased charges by $2871. For the 150 to 180
      tracheostomies done each year at our institution utilization of the open
      technique at the bedside results in a cost savings of approximately $31,500 and a
      charge savings of $109,000 compared with the percutaneous dilatational
      tracheostomy. Both the open bedside and percutaneous dilatational methods are
      reasonable and safe options. However, the open bedside tracheostomy is a better
      utilization of resources and is more cost effective, and it is the procedure of
      choice at our institution.

PMID- 11307994
TI  - Intraoperative and early postoperative gastric intramucosal pH predicts morbidity
      and mortality after major abdominal surgery.
AB  - The present study was undertaken to investigate the correlation between the
      intraoperative and postoperative gastric intramucosal pH (pHi) with important
      perioperative variables and to explore any potential relationship of the measured
      pHi with the patients' postoperative course. A prospective study was carried out
      in a group of 48 patients who underwent major abdominal operations over an 8
      month period at St. John Hospital and Medical Center. An automated air tonometer
      was used for gastric pHi monitoring. Twenty-eight elective and 20 emergency
      abdominal operations were performed in 23 men and 25 women. Twenty-six patients
      (54%) required postoperative hospitalization in the Intensive Care Unit (ICU).
      Seventeen patients (35%) developed early postoperative complications. The non-ICU
      and ICU mortality rates were 4.5 and 19.2 per cent respectively. The mean
      intraoperative pHi (pHiOR) and postoperative pHi (pHiPO) ranged between 7.03 and
      7.58 (7.38+/-0.12) and 6.89 and 7.56 (7.35+/-0.12) respectively (mean +/-
      standard deviation). There was a significant decrease of the gastric pHi at the
      first hour intraoperatively compared with the pHi after induction to anesthesia
      (7.44 vs 7.38+/-0.14, P < 0.001). Patients who underwent emergent abdominal
      procedures were characterized by lower pHiOR and pHiPO values (7.43+/-0.08 vs
      7.30+/-0.13 and 7.39+/-0.84 vs 7.30+/-0.15, P < 0.001 and P < 0.05). Similarly
      patients who required surgical ICU admission had significantly lower pHiOR and
      pHiPO measurements (7.3+/-0.12 and 7.28+/-0.12) compared with the rest (7.46+/
      0.06 and 7.43+/-0.06; P < 0.001). Overall, lower pHiOR and pHiPO values were
      associated with the occurrence of postoperative complications (P < 0.001), the
      postoperative mortality (P < 0.001), the requirement for postoperative mechanical
      ventilator (P < 0.001) and its duration (P < 0.001), longer ICU stay (P < 0.001),
      and prolonged hospitalization (P < 0.05). Evidence of intraoperative and early
      postoperative gastric mucosal ischemia (pHiOR and pHiPO < or = 7.32) was observed
      in 12 (25%) and 15 (31%) patients respectively. The incidence of postoperative
      complications and the mortality rate were higher in this group of patients (P <
      0.001). At a cutoff point of 7.32 gastric pHiOR gave a sensitivity of 69 per cent
      and specificity of 97 per cent for predicting postoperative complications as well
      as a sensitivity and specificity of 67 per cent and 81 per cent for predicting
      death. Intraoperative and early postoperative gastric pHi is a reliable predictor
      of patient outcome after major abdominal operations. Splanchnic ischemia may play
      an important role in determining early complications and survival; therapy guided
      by the gastric pHi might improve outcome.

PMID- 11307995
TI  - Refractory renal hyperparathyroidism: clinical features and outcome of surgical
      therapy.
AB  - Despite improvements in medical management parathyroidectomy has an important
      role in treatment of refractory renal hyperparathyroidism (HPT). The medical
      records of all patients who underwent parathyroidectomy from 1991 through 2000
      were reviewed to determine the clinical and laboratory features and outcomes of
      treatment in patients with renal versus primary HPT. Twenty-one of 92 patients
      who underwent parathyroidectomy had renal HPT with a mean age of 47+/-3 years
      compared with 56+/-2 years for patients with primary HPT (P < 0.05). Clinical
      manifestations included osteodystrophy (19), pruritus (six), extraosseous
      calcification (three), and calciphylaxis (one). Parathyroid hormone, phosphorus,
      and alkaline phosphatase levels and weights of excised glands were higher in
      renal versus primary HPT (P < 0.05). Supernumerary glands were found in three
      patients (14%) with renal HPT and none of nine patients with primary parathyroid
      hyperplasia. After surgical therapy persistent or recurrent HPT occurred in three
      (14%) patients with renal and one (1.4%) patient with primary HPT (P < 0.05).
      Postoperative hypocalcemia occurred in 20 (95%) patients with renal HPT all of
      whom required intravenous calcium, compared with 25 (35%) patients with primary
      HPT (P < 0.05) of whom only three (4%) required intravenous calcium (P < 0.05).
      In contrast to those with primary HPT patients with renal HPT are younger and
      more likely to have severe osteodystrophy, postoperative hypocalcemia, and
      persistent or recurrent HPT.

PMID- 11307996
TI  - Perioperative factors as predictors of operative mortality and morbidity in
      pneumonectomy.
AB  - Pneumonectomy for lung cancer is associated with significant morbidity and
      mortality. Risk factors for the morbidity and mortality have been reported, but
      consistent conclusive data are undetermined. Current accepted 30-day mortality
      rates for pneumonectomy range from 7 to 11 per cent. The objective of this study
      is to determine whether various perioperative factors can serve as predictors of
      morbidity and mortality in pneumonectomy patients and to review outcome data on
      patients undergoing pneumonectomy for lung cancer. A total of 105 patients
      undergoing pneumonectomy for lung cancer from 1988 through 1998 are studied in a
      retrospective chart review. The main outcome measure is the 30-day operative
      mortality and morbidity. Complications occurring in 10 per cent or more of the
      patients included atrial fibrillation (33.3%), respiratory failure (23.8%),
      pneumonia (21.9%), and bronchopleural fistula (12.4%). The 30-day mortality rate
      was 10.5 per cent (11 deaths). By Fisher's exact test for Chi-square only three
      statistically significant mortality factors were identified: respiratory failure
      (P < 0.021), sepsis (P < 0.008), and male sex (P < 0.031); respiratory failure,
      sepsis, and sex were predictors of death. Significant correlation could not be
      made to predict postoperative morbidity. Overall long-term clinical outcome for
      pneumonectomy as lung cancer treatment was poor. Clinical judgment remains an
      essential factor when considering pneumonectomy as an option for lung cancer
      treatment.

PMID- 11307997
TI  - Objective Structured Clinical Examination technical skill stations correlate more
      closely with postgraduate year level than do clinical skill stations.
AB  - Validity of an examination format is supported by its ability to distinguish
      levels of training among examinees. The Objective Structured Clinical Examination
      (OSCE) is a developing format generally composed of various types of task
      oriented stations used to evaluate clinical skills of students and residents. The
      ideal composition of OSCE stations to maximize validity has not been determined.
      We examined the relative correlation between selected types of stations and level
      of resident postgraduate year (PGY). A 12-station OSCE was administered to
      surgical residents of all PGY levels at a university program. Individual station
      scores were correlated with PGY level. The overall correlation of the total
      examination score with PGY level was good (R = 0.681). Technical skill stations
      exhibited a significantly greater correlation with PGY level (0.679 vs 0.203) as
      compared with clinical skill stations (P < 0.05). These data suggest that
      technical skill evaluation is more sensitive in distinguishing level of training
      of surgical residents than is clinical skill evaluation.

PMID- 11307998
TI  - Decreased recurrent carotid stenosis by routine patching and intraoperative
      scanning.
AB  - Our objective was to review the results of carotid endarterectomies (CEAs) with
      Dacron patch angioplasty and intraoperative color-flow duplex scanning (CFS). In
      a 3-year period, patients who underwent CEA with Dacron patch angioplasty and
      intraoperative CFS were studied. We excluded patients who had primary closure,
      vein patch, and redo endarterectomy. Serial CFS was obtained first in the early
      postoperative period (one day to 3 weeks), then at 6 months, and then yearly.
      Intraoperative CFS abnormalities were classified as major, requiring immediate
      revision, or minor, which were observed. The diagnosis of recurrent stenosis by
      US was based on the detection of an increased peak systolic frequency (>8000 MHz)
      or velocity (>250 cm/second) in the internal carotid artery. There were 212 CEAs
      performed in 200 patients (128 men and 84 women) included in this study. Three
      patients (1.4%) awoke with a stroke, two (0.94%) had transient ischemic attacks,
      and three (1.4%) developed transient hypoglossal nerve paresis. Intraoperative
      CFS showed a major defect that required an immediate revision in six patients
      (2.8%). Minor abnormalities were detected in another 41 patients (19.3%), but no
      revision was necessary. In follow-up three patients were identified with a severe
      recurrent carotid stenosis (>80%) and they underwent redo CEA. This rate of
      recurrence (1.4%) is significantly lower than the rate we had previously reported
      in a larger study (82 of 1209, 6.8%; P = 0.003). We conclude that the combined
      use of Dacron patch angioplasty and intraoperative CFS after CEA is associated
      with a low perioperative morbidity and a low incidence of recurrent stenosis in
      the first 2 years after operation.

PMID- 11307999
TI  - Telemedicine in vascular surgery: does it work?
AB  - Telemedicine (TM) using closed-circuit television systems allows specialists to
      evaluate patients at remote sites. Because an integral part of the vascular
      examination involves palpation of peripheral pulses the applicability of TM for
      the evaluation of vascular surgery patients is open to question. This study was
      carried out to test the hypothesis that TM is as effective as direct patient
      examination for the development of a care plan in vascular patients. Sixty-four
      vascular evaluations were done in 32 patients. The patients presented with a
      variety of vascular problems and were seen in regularly scheduled rural outreach
      vascular clinics. Two faculty vascular surgeons evaluated each patient; one was
      on site and the second, using TM, remained at the medical center. Each surgeon
      was blinded to the other's findings. The TM physician was aided by a nonphysician
      assistant, who obtained blood pressures, utilized a continuous-wave Doppler
      probe, positioned the patient, and operated the TM equipment. The results of each
      surgeon's evaluations were compared. Patient and physician satisfaction with the
      TM evaluation was appraised by questionnaires. Eight patients were seen for
      initial evaluations; 24 patients were seen for follow-up visits. Patients were
      seen with a variety of diagnoses, including aneurysm (seven), cerebrovascular
      disease (five), lower extremity occlusive disease (13), multiple vascular
      problems (three), and other disease (four). The average duration for the TM and
      on-site evaluations were 20.6+/-1.4 and 19.0+/-1.3 minutes, respectively (P = not
      significant). Physician concordance, as determined by treatment recommendations,
      was the same in 29 (91%) patients. Physician confidence in the ability to obtain
      an accurate history via TM was rated as excellent in 97 per cent; confidence in
      the TM physical examination was rated as excellent in 70 per cent. All patients
      rated the TM evaluation as the "same as" or "better than" the on-site
      examination, and all indicated a preference for being seen locally using TM as
      opposed to traveling to a regional medical center. We conclude that the TM
      evaluation of vascular patients is accurate and is as effective as on-site
      evaluations for a variety of vascular problems. Important adjuncts to enhance the
      success of a TM evaluation are physician experience with the technology and the
      presence of a knowledgeable on-site assistant. This technology can be easily
      adapted to other clinical situations.

PMID- 11308000
TI  - Laparoscopic versus conventional live donor nephrectomy: experience in a
      community transplant program.
AB  - Fifty-nine consecutive patients underwent live donor nephrectomy for
      transplantation. Twenty-nine patients (Group I) had open kidney procurement, and
      30 patients (Group II) had laparoscopic procurement. The mean operative time in
      Group I was 2:30 hours (range 1:55-2:59), whereas in Group II it was 3:01 hours
      (1:54-5:21). All kidneys functioned immediately after transplantation. The
      average warm ischemia time was not calculated in Group I; it was 3.9 minutes (2
      15) in Group II. Intraoperative complications occurred in two patients in Group
      II. One patient had bleeding from an accessory renal artery. The second patient
      had a tear in the splenic capsule. No ureteral complications occurred in either
      group. Postoperatively one patient in Group I developed incisional hernia, one
      developed pneumothorax, and two developed atelectasis. In Group II one patient
      developed pancreatitis, one developed flank ecchymosis, and two had suprapubic
      wound hematomas. Using the laparoscopic approach the hospital stay decreased from
      4.1 to 1.27 days (69%) (P < 0.001) and return to work decreased from 28.4 to 14.8
      days (49%) (P < 0.01). Live donation increased by 67 per cent. We conclude that
      the laparoscopic procurement of kidneys for transplantation compares well with
      the open method. It offers several advantages that may increase the living donor
      pool.

PMID- 11308001
TI  - Emergency cricothyrotomy: long-term results.
AB  - In 1996 we reviewed the literature and reported on our own series of emergency
      cricothyrotomy (EC) patients. The success rate in obtaining an airway was very
      good. The survival rate was also acceptable. However, there have been no reports
      of long-term results of EC. We retrospectively reviewed the long-term results in
      27 survivors of 65 original EC patients. The average length of follow-up was 37
      months (1-77 months). In 13 patients no airway problems were found. The remaining
      14 patients had only minor problems such as hoarse voice and mild untreated
      stenosis. Of these 27 patients, however, only seven were doing well. Five
      patients had relatively minor problems such as the need for a gastrostomy tube,
      minor shortness of breath, or minor neurological problems. Fifteen patients had
      major problems: cervical spine injuries, changes in mental status, need for
      permanent nursing home care, seizure disorders, or injuries that precluded their
      working. In most cases these problems were due to the underlying disease process.
      EC is effective in obtaining an airway with a low incidence of later severe
      airway problems. However, many of these patients do poorly overall.

PMID- 11308002
TI  - Adult intussusception due to a malignant polyp: a case report.
AB  - Intussusception is primarily a disease of childhood; only about 5 to 10 per cent
      of cases occur in adults. In contrast to childhood intussusception 90 per cent of
      adults have an associated pathologic process, usually a malignant lesion. Adult
      cases do not have the classical symptoms and diagnosis may be difficult. CT scan
      and barium studies are the most useful diagnostic methods. We report a very rare
      case of adult ileocecocolic intussusception caused by a pedunculated malignant
      polyp of the cecum and review the clinical features of intussusception.

PMID- 11308003
TI  - Blood pressure effects of thoracic gunshot wounds: the role of bullet image
      diameter.
AB  - Differences in handgun bullet diameter, expansion, and penetration (no exit)
      versus perforation (with exit) may be the cause of variable blood pressure
      effects after thoracopulmonary injury. Forty nonlethal isolated gunshot wounds of
      the thorax were evaluated excluding wounds of the heart, great vessels, and
      spinal cord. Chest radiographs were assessed for bullet base diameter, bullet
      expansion, and wound length. Large bullets were defined as having radiographic
      base images of 9 mm or more in diameter. Systolic blood pressures were compared
      between penetrating large and small bullet groups and with perforating wounds.
      Response times and demographics were compared. Wounds caused by large bullet
      penetration resulted in lower initial systolic blood pressures than wounds caused
      by small bullet penetration (98 vs 125 mm Hg, P < 0.05). The average age,
      transport time, and wound length were similar among the bullet groups. We
      conclude that penetrating thoracopulmonary wounds caused by large bullets
      resulted in lower initial systolic blood pressure.

PMID- 11308004
TI  - Twelve-year experience with the Thow long intestinal tube: a means of preventing
      postoperative bowel obstruction.
AB  - The purpose of this study was to determine the effectiveness of the Thow long
      intestinal tube (LIT) for prevention of postoperative adhesive small bowel
      obstruction (ASBO) and to compare the Thow tube with other LITs. The charts of
      all patients who had placement of a Thow tube between January 1986 and November
      1998 were reviewed. Thirty-four patients ranging in age from 9 to 86 years (mean
      57.9) were included in the study. Twenty-five were contacted by phone for long
      term follow-up. Twenty-nine patients had undergone previous abdominal surgery,
      and in 11 of 29 the previous surgery was for ASBO. Indications for surgery and
      Thow tube placement included: bowel obstruction (25), perforated viscus (five),
      carcinomatosis (two), colitis (one), and atonic bowel (one). Review of the
      operative notes revealed no difficulty in advancing the Thow tube in 32 of 34
      patients (94%). Thow tube-related complications occurred in nine patients (25%).
      All complications were associated with the gastrostomy site, and only one patient
      required surgery for the complication. Two (5.9%) patients developed recurrent
      obstruction during a mean follow-up of 52 months. In one patient the obstruction
      was caused by adhesions and in another it was the result of an intra-abdominal
      abscess. Of 23 patients treated for ASBO at the time of Thow tube placement no
      patient (0%) developed recurrent ASBO during the follow-up period (total 110.5
      patient-years). This study along with a review of the literature suggests that
      LITs decrease the risk of recurrent ASBO. The Thow tube, however, is easily
      placed and is associated with fewer and less severe complications than other
      LITs.

PMID- 11308005
TI  - Transfemoral extraction of an intracardiac bullet embolus.
AB  - Missiles may reach the heart via direct penetration of the thoracic cavity or
      indirectly by means of the venous circulation. Often the hemodynamic stability of
      the patient dictates the approach that is used not only to retrieve the
      projectile but also to repair associated life-threatening injuries. The case of a
      40-year-old man with an intracardiac missile after a gunshot wound to the right
      gluteal area is presented along with the transfemoral technique used to recover
      an intracardiac projectile. This approach may be used instead of thoracotomy for
      missile extraction in stable patients.

PMID- 11308007
TI  - Effect of pneumoperitoneal pressure on tumor dissemination and tumor recurrence
      at port-site and midline incisions.
AB  - Over the past several years numerous cases of port site tumor recurrence after
      laparoscopic resection of a cancerous tissue have been reported. Possible
      mechanisms for tumor seeding include tumor removal, contaminated instruments,
      pneumoperitoneum, and aerosolization of tumor cells. This experiment examined the
      relationship among trocar contamination, aerosolization, and tumor recurrence
      with increasing pneumoperitoneal pressure using a hamster model. Increased
      pneumoperitoneal pressure significantly increased both instrument contamination
      and tumor recurrence at midline and port site incisions. Interestingly,
      increasing pneumoperitoneal pressure had no significant effect on the number of
      aerosolized tumor cells. The results reaffirm that the use of a reduced
      pneumoperitoneum or gasless laparoscopy may significantly lower port site tumor
      recurrence.

PMID- 11308006
TI  - Defining the learning curve for the Focused Abdominal Sonogram for Trauma (FAST)
      examination: implications for credentialing.
AB  - Focused Abdominal Sonogram for Trauma (FAST) examination is being used
      increasingly for the torso evaluation of injured patients. In a controlled
      setting using peritoneal dialysis patients as models for injured patients with
      free fluid we hypothesized that more experienced providers would perform FAST
      with greater accuracy. Twelve fellow or attending level trauma surgeons, two
      radiologists, and one ultrasound technician were studied for their ability to
      detect intraperitoneal fluid (0-1600 cm3) in nine peritoneal dialysis patients
      with two different volumes of dialysate/patient. FAST experience with injured
      patients was defined as minimal (<30 patients examinations), moderate (30-100),
      or extensive (>100). All surgeons had participated in a didactic/practical course
      before the study. Test results were reported as "+" or "-" by the participant;
      "+" results were further quantified by volume. The sensitivity of those in the
      minimal-, moderate-, and extensive-experience to detect <1 L was 45, 87, and 100
      per cent, respectively; the accuracy in detecting dialysate volume within 250 cm3
      was 38, 63, and 90 per cent, respectively. In this controlled setting the
      accuracy of FAST particularly in diagnosing smaller volumes, as well as the
      ability to quantify volume, improves with experience. The learning curve for FAST
      starts to flatten out at 30 to 100 examinations. Training and credentialing
      policies should consider these findings to optimize patient care.

PMID- 11308008
TI  - Idiopathic spontaneous intraperitoneal hemorrhage: a clinical update on abdominal
      apoplexy in the year 2001.
AB  - Idiopathic spontaneous intraperitoneal hemorrhage is a rare and often fatal
      condition that has been historically referred to as abdominal apoplexy. The
      presentation varies widely, and preoperative diagnosis is seldom obtained.
      Immediate surgical exploration remains the treatment of choice. At the time of
      exploration a through examination of the visceral arteries and solid organs
      should be done, as these are common sites for intra-abdominal bleeding. Often the
      site of hemorrhage cannot be localized at time of surgery despite thorough
      exploration. Today a postoperative diagnosis can often be confirmed and treated
      with interventional radiology. In rare cases the site of bleeding remains unknown
      despite intraoperative exploration and radiographic studies.

PMID- 11308009
TI  - Treatment of severe acute respiratory distress syndrome: a final report on a
      phase I study.
AB  - Adult respiratory distress syndrome (ARDS) has a high mortality. Its only
      effective treatment is respiratory therapy. If this fails mortality is probably
      100 per cent. No other treatment for ARDS has proved effective including "magic
      bullets." Twenty patients suffering from ARDS secondary to trauma and/or sepsis
      failed to respond to treatment with mechanical ventilation and positive end
      expiratory pressure. On the assumption that disseminated intravascular
      coagulation initiates ARDS by occluding the pulmonary microcirculation with
      microclots, the patients were treated with plasminogen activators. The patients
      responded with significant improvement in partial pressure of oxygen in arterial
      blood. No bleeding occurred and clotting parameters remained normal. We conclude
      that ARDS can be safely treated with plasminogen activator.

PMID- 11308010
TI  - Jejunoileal causes of overt gastrointestinal bleeding: diagnosis, management, and
      outcome.
AB  - Major bleeding from the small intestine is uncommon and difficult to localize. We
      examined its etiologies and assessed available diagnostic and therapeutic
      approaches. The records of all adults undergoing operation for small intestinal
      hemorrhage over a 10-year period (1/89-12/98) were reviewed. There were eight men
      and four women with a mean age of 54 years. Six patients presented with
      arteriovenous malformations. Preoperative diagnosis was by endoscopy (three of
      six), scintigraphy (two of two), and/or angiography (two of six). Intraoperative
      panendoscopy was used for localization in 5 cases. Three other patients had
      tumors (leiomyoma, leiomyosarcoma, and adenocarcinoma) by CT scan (two) and/or
      scintigraphy (two). All were resected but one patient died of recurrence. Two
      patients underwent resection of a Meckel's diverticulum, one after angiographic
      diagnosis. Another patient with Crohn's disease had a positive angiogram and
      colonoscopy before resection. There were no operative deaths but major morbidity
      occurred in five patients (42%) and hospitalization averaged 17 days. We conclude
      that jejunoileal lesions are a rare cause of intestinal bleeding but can be
      associated with substantial morbidity. Arteriovenous malformations and tumors
      remain the most common causes. An accurate diagnosis and definitive management
      depend on selective preoperative imaging and judicious operative exploration.

PMID- 11308011
TI  - Reliability of histologic diagnosis of breast cancer with stereotactic vacuum
      assisted biopsy.
AB  - The purpose of this study was to determine the accuracy of 11-gauge stereotactic
      vacuum-assisted breast biopsy (SVAB) for the diagnosis of breast cancer.
      Percutaneous biopsies of 426 suspicious breast lesions in 365 patients using 11
      gauge SVAB were performed between September 1996 and June 1998. Of these biopsies
      59 (13.8%) resulted in a diagnosis of breast carcinoma and 56 (95%) were
      surgically excised. These 56 lesions constitute the basis of this study.
      Pathology of SVAB and surgically excised tissue of the 56 carcinomas as well as
      imaging findings were correlated. At percutaneous biopsy 34 (61%) lesions
      demonstrated ductal carcinoma in situ (DCIS) and 22 (39%) invasive carcinomas.
      Surgical excision demonstrated the presence of an invasive cancer in three
      lesions percutaneously diagnosed as DCIS (9%; confidence interval 2-24%). No
      residual carcinoma was surgically demonstrated in seven (12.5%) lesions.
      Sensitivity of 11-gauge SVAB for the diagnosis of invasion in breast cancer was
      88 per cent. Using SVAB the diagnosis of invasive carcinoma is reliable. However,
      a percutaneous finding of DCIS does not exclude the presence of invasion in 9 per
      cent of cases as confirmed by subsequent surgery. Using SVAB 12.5% of carcinomas
      are completely excised.

PMID- 11308013
TI  - O-glycosylation of the mucin type.
AB  - While only about ten percent of the databank entries are defined as
      glycoproteins, it has been estimated recently that more than half of all proteins
      are glycoproteins. Mucin-type O-glycosylation is a widespread post-translational
      modification of proteins found in the entire animal kingdom, but also in higher
      plants. The structural complexity of the chains initiated by O-linked GalNAc
      exceeds that of N-linked chains by far. The process during which serine and
      threonine residues of proteins become modified is confined to the cis to trans
      Golgi compartments. The initiation of this process by peptidyl GalNAc
      transferases is ruled by the sequence context of putative O-glycosylation sites,
      but also by epigenetic regulatory mechanisms, which can be mediated by enzyme
      competition. The cellular repertoir of glycosyltransferases with their distinct
      donor sugar and acceptor sugar specificities, their sequential action at highly
      ordered surfaces, and their localizations in subcompartments of the Golgi finally
      determine the cell-specific O-glycosylation profile. Dramatic alterations of the
      glycosylation machinery are observed in cancer cells, resulting in aberrantly O
      glycosylated proteins that expose previously masked peptide motifs and new
      antigenic targets. The functional aspects of O-linked glycans, which comprise
      among many others their potential role in sorting and secretion of glycoproteins,
      their influence on protein conformation, and their multifarious involvement in
      cell adhesion and immunological processes, appear as complex as their structures.

PMID- 11308015
TI  - Congenital disorders of glycosylation: glycosylation defects in man and
      biological models for their study.
AB  - Several inherited disorders affecting the biosynthetic pathways of N-glycans have
      been discovered during the past years. This review summarizes the current
      knowledge in this rapidly expanding field and covers the molecular bases of these
      disorders as well as their phenotypical consequences.

PMID- 11308016
TI  - Mitochondrial single-stranded DNA-binding proteins: in search for new functions.
AB  - During the evolution of the eukaryotic cell, genes encoding proteins involved in
      the metabolism of mitochondrial DNA (mtDNA) have been transferred from the
      endosymbiont into the host genome. Mitochondrial single-stranded DNA-binding
      (mtSSB) proteins serve as an excellent argument supporting this aspect of the
      endosymbiotic theory. The crystal structure of the human mtSSB, together with an
      abundance of biochemical and genetic data, revealed several exciting features of
      mtSSB proteins and enabled a detailed comparison with their prokaryotic
      counterparts. Moreover, identification of a novel member of the mtSSB family,
      mitochondrial telomere-binding protein of the yeast Candida parapsilosis, has
      raised interesting questions regarding mtDNA metabolism and evolution.

PMID- 11308014
TI  - Glycoproteins from insect cells: sialylated or not?
AB  - Our growing comprehension of the biological roles of glycan moieties has created
      a clear need for expression systems that can produce mammalian-type
      glycoproteins. In turn, this has intensified interest in understanding the
      protein glycosylation pathways of the heterologous hosts that are commonly used
      for recombinant glycoprotein expression. Among these, insect cells are the most
      widely used and, particularly in their role as hosts for baculovirus expression
      vectors, provide a powerful tool for biotechnology. Various studies of the
      glycosylation patterns of endogenous and recombinant glycoproteins produced by
      insect cells have revealed a large variety of O- and N-linked glycan structures
      and have established that the major processed O- and N-glycan species found on
      these glycoproteins are (Gal beta1,3)GalNAc-O-Ser/Thr and Man3(Fuc)GlcNAc2-N-Asn,
      respectively. However, the ability or inability of insect cells to synthesize and
      compartmentalize sialic acids and to produce sialylated glycans remains
      controversial. This is an important issue because terminal sialic acid residues
      play diverse biological roles in many glycoconjugates. While most work indicates
      that insect cell-derived glycoproteins are not sialylated, some well-controlled
      studies suggest that sialylation can occur. In evaluating this work, it is
      important to recognize that oligosaccharide structural determination is tedious
      work, due to the infinite diversity of this class of compounds. Furthermore,
      there is no universal method of glycan analysis; rather, various strategies and
      techniques can be used, which provide glycobiologists with relatively more or
      less precise and reliable results. Therefore, it is important to consider the
      methodology used to assess glycan structures when evaluating these studies. The
      purpose of this review is to survey the studies that have contributed to our
      current view of glycoprotein sialylation in insect cell systems, according to the
      methods used. Possible reasons for the disagreement on this topic in the
      literature, which include the diverse origins of biological material and
      experimental artifacts, will be discussed. In the final analysis, it appears that
      if insect cells have the genetic potential to perform sialylation of
      glycoproteins, this is a highly specialized function that probably occurs rarely.
      Thus, the production of sialylated recombinant glycoproteins in the baculovirus
      insect cell system will require metabolic engineering efforts to extend the
      native protein glycosylation pathways of insect cells.

PMID- 11308017
TI  - Do rodent and human brains have different N-glycosylation patterns?
AB  - A large number of studies on the structure of N-glycosidically linked
      oligosaccharides from glycoproteins of different organs and/or different species
      have been carried out in the past using various combinations of techniques such
      as monosaccharide analysis, permethylation, peracteylation, exoglycosidase
      sequencing, normal and reversed phase HPLC, mass spectrometry and nuclear
      magnetic resonance spectroscopy. Although it is widely accepted that the
      processing of N-glycans in the ER and Golgi of mammalian cells follows the same
      principal metabolic rules, analyses have revealed that the glycosylation pattern
      of a particular protein may differ depending on the cell type in which it is
      expressed. N-glycans from brain glycoproteins have been shown to include a
      variety of hybrid- and complex-type structures with structural features that are
      not so commonly found on glycoproteins from other organs and which have,
      therefore, been classified as 'brain-specific'. Comparison of the N-glycans of
      glycoproteins from homogenates of rat, mouse and human brains confirm that, in
      general, glycoproteins from human brain show a similar profile of brain-specific
      N-glycans as glycoproteins from mouse and rat brain.

PMID- 11308018
TI  - The liver flukes Fasciola gigantica and Fasciola hepatica express the leucocyte
      cluster of differentiation marker CD77 (globotriaosylceramide) in their tegument.
AB  - Glycosphingolipids from the parasitic liver flukes Fasciola gigantica and
      Fasciola hepatica were isolated and their carbohydrate moieties were structurally
      analysed by methylation analysis, exoglycosidase treatment, on-target
      exoglycosidase cleavage and matrix-assisted laser desorption/ionisation time-of
      flight mass spectrometry. For both liver fluke species, the ceramide
      monohexosides Gal1-ceramide and Glc1-ceramide were found in relative amounts of
      1.0 to 0.1, respectively. From F. gigantica, the ceramide dihexoside was isolated
      in sufficient amounts to be structurally determined as lactosylceramide, Gal
      beta4-Glc1-ceramide, while for both liver fluke species the ceramide trihexoside
      was shown to be Gal alpha4Gal beta4-Glc1-ceramide, which is designated as either
      globotriaosylceramide, Pk-blood group antigen or CD77 leucocyte cluster of
      differentiation antigen. To our knowledge, this is the first report on the
      expression of globo-series glycosphingolipids in non-mammalian species. Ceramide
      analysis of ceramide monohexosides yielded as major components octadecanoic and 2
      hydroxyoctadecanoic fatty acids together with C18- and C20-phytosphingosines. By
      the use of an anti-CD77 monoclonal antibody and the Escherichia coli Shiga toxin
      B1 subunit, globotriaosylceramide could be immunolocalised to the tegument of F.
      hepatica cryosections. The sharing of CD77 between liver flukes and their
      mammalian hosts fits in with the concept of molecular mimicry, which is closely
      parallel to the established imitation of host CD15 (Lewis X) displayed by the
      blood fluke Schistosoma mansoni.

PMID- 11308019
TI  - Cloning and expression of Drosophila melanogaster UDP-GlcNAc:alpha-3-D-mannoside
      beta1,2-N-acetylglucosaminyltransferase I.
AB  - A TBLASTN search of the Drosophila melanogaster expressed sequence tag (EST)
      database with the amino acid sequence of human UDP-N-acetylglucosamine:alpha-3-D
      mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I, EC 2.4.1.101) as
      probe yielded a clone (GM01211) with 56% identity over 36 carboxy-terminal amino
      acids. A 550 base pair (bp) probe derived from the EST clone was used to screen a
      Drosophila cDNA library in lambda-ZAP II and two cDNAs lacking a start ATG codon
      were obtained. 5'-Rapid amplification of cDNA ends (5'-RACE) yielded a 2828 bp
      cDNA containing a full-length 1368 bp open reading frame encoding a 456 amino
      acid protein with putative N-terminal cytoplasmic (5 residues) and hydrophobic
      transmembrane (20 residues) domains. The protein showed 52% amino acid sequence
      identity to human GnT I. This cDNA, truncated to remove the N-terminal
      hydrophobic domain, was expressed in the baculovirus/Sf9 system as a secreted
      protein containing an N-terminal (His)6 tag. Protein purified by adsorption to
      and elution from nickel beads converted Man alpha1-6(Man alpha1-3)Man beta-octyl
      (M3-octyl) to Man alpha1-6(GlcNAc beta1-2Man alpha1-3)Man beta-octyl. The Km
      values (0.7 and 0.03 mM for M3-octyl and UDP-GlcNAc respectively), temperature
      optimum (37 degrees C), pH optimum (pH 5 to 6) and divalent cation requirements
      (Mn > Fe, Mg, Ni > Ba, Ca, Cd, Cu) were similar to mammalian GnT I. TBLASTN
      searches of the Berkeley Drosophila Genome Project database with the Drosophila
      GnT I cDNA sequence as probe allowed localization of the gene to chromosomal
      region 2R; 57A9. Comparison of the cDNA and genomic DNA sequences allowed the
      assignment of seven exons and six introns; all introns showed GT-AG splice site
      consensus sequences. This is the first insect GnT I gene to be cloned and
      expressed.

PMID- 11308020
TI  - Pathways of mucin O-glycosylation in normal and malignant rat colonic epithelial
      cells reveal a mechanism for cancer-associated Sialyl-Tn antigen expression.
AB  - The Sialyl-Tn antigen (Sialyl alpha-Ser/Thr) is expressed as a cancer-associated
      antigen on the surface of cancer cells. Its presence is associated with a poor
      prognosis in patients with colorectal and other cancers. We previously reported
      that Sialyl-Tn expression in LSC human colon cancer cells could be explained by a
      specific lack of the activity of core 1 beta3-Gal-transferase (Brockhausen et
      al., Glycoconjugate J. 15, 595-603, 1998) and an inability to synthesize the
      common O-glycan core structures. To support this mechanism, or find other
      mechanisms to explain Sialyl-Tn antigen expression, we investigated the O
      glycosylation pathways in clonal rat colon cancer cell lines that were selected
      for positive or negative expression of Sialyl-Tn antigen, and compared these
      pathways to those in normal rat colonic mucosa. Normal rat colonic mucosa had
      very active glycosyltransferases synthesizing O-glycan core structures 1 to 4.
      Several sialyl-, sulfo- and fucosyltransferases were also active. An M type core
      2 beta6-GlcNAc-transferase was found to be present in rat colon mucosa and all of
      the rat colon cancer cells. O-glycosylation pathways in rat colon cancer cells
      were significantly different from normal rat colonic mucosa; for example, rat
      colon cancer cells lost the ability to synthesize O-glycan core 3. All rat colon
      cancer cell lines, regardless of the Sialyl-Tn phenotype, expressed
      glycosyltransferases assembling complex O-glycans of core 1 and core 2 structures
      (unlike human LSC colon cancer cells which lack core 1 beta3-Gal-transferase
      activity). It was the activity of CMP-sialic acid:GalNAc-mucin alpha6
      sialyltransferase that coincided with Sialyl-Tn expression. Sialyl-Tn negative
      cells had a several fold higher activity of core 2 beta6-GlcNAc-transferase which
      synthesizes complex O-glycans that may mask adjacent Sialyl-Tn epitopes. The
      results suggest a new mechanism controlling Sialyl-Tn expression in cancer cells.

PMID- 11308021
TI  - 6-O-sulfo de-N-acetylsialyl Lewis X as a novel high-affinity ligand for human L
      selectin: total synthesis and structural characterization.
AB  - Total synthesis and structural characterization of a novel 6-O-sulfo de-N
      acetylsialyl Lewis X, which was originally discovered as a minor by-product of
      the parent 6-O-sulfo N-acetylsialyl Lewis X, a high-affinity endogenous ligand
      for human L-selectin, are described. The total synthesis has been achieved by a
      highly efficient, regio- and alpha-stereoselective glycosylation of N
      trifluoroacetylneuraminic acid, selective protections of the 3- and 6-hydroxyl
      groups of N-acetylglucosamine that undergo fucosylation and sulfation, and
      construction of the glycolipid structure containing a ceramide. The structure of
      6-O-sulfo de-N-acetylsialyl Lewis X ganglioside was characterized by fast atom
      bombardment mass spectrometry (FAB-MS).

PMID- 11308022
TI  - Segregation of gangliosides GM1 and GD3 on cell membranes, isolated membrane
      rafts, and defined supported lipid monolayers.
AB  - Lateral assemblies of sphingolipids, glycosphingolipids and cholesterol, termed
      rafts, are postulated to be present in biological membranes and to function in
      important cellular phenomena. We probed whether rafts are heterogeneous by
      determining the relative distribution of two gangliosides, GM1 and GD3, in
      artificial supported monolayers, in intact rat primary cerebellar granule
      neurones, and in membrane rafts isolated from rat cerebellum. Fluorescence
      resonance energy transfer (FRET) using fluorophore-labelled cholera toxin B
      subunit (which binds GM1) and mAb R24 (which binds GD3) revealed that GM1
      spontaneously self-associates but does not co-cluster with GD3 in supported
      monolayers and on intact neurones. Cholera toxin and immunocytochemical labelling
      of isolated membrane rafts from rat cerebellum further demonstrated that GM1 does
      not co-localise with GD3. Furthermore, whereas the membrane raft resident
      proteins Lyn and caveolin both co-localise with GD3 in isolated membrane rafts,
      GM1 appears in separate and distinct aggregates. These data support prior reports
      that membrane rafts are heterogeneous, although the mechanisms for establishing
      and maintaining such heterogeneity remain to be determined.

PMID- 11308023
TI  - Structural characterization of fucose-containing oligosaccharides by high
      performance liquid chromatography and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry.
AB  - Eight pyridylamino (PA) derivatives of fucose-containing oligosaccharides, which
      occur as free oligosaccharides in human milk and also are derived from
      glycosphingolipids, have been analyzed by high-performance liquid chromatography
      (HPLC) on normal-phase and reversed-phase columns, and by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Six out of
      eight PA-oligosaccharides were clearly separated by both normal- and reversed
      phase HPLC at a column temperature of 40 degrees C, but two PA-oligosaccharides,
      lacto-N-fucopentaose II [Gal beta1-3(Fuc alpha1-4)GlcNAc beta1-3Gal beta1-4GIcPA]
      and lacto-N-fucopentaose III [Gal beta1-4(Fuc alpha1-3)GlcNAc beta1-3Gal beta1
      4GIcPA], were not separated. The two unresolved PA-oligosaccharides were finally
      separated by reversed-phase HPLC at a column temperature of 11 degrees C. MALDI
      TOF mass spectra of PA-oligosaccharides demonstrated pseudo-molecular ions as the
      predominant signals, therefore information about the molecular mass of each PA
      oligosaccharide was easily obtained. Post-source decay (PSD) MALDI-TOF mass
      spectra of PA-oligosaccharides gave information about the carbohydrate sequences
      and carbohydrate species of each PA-oligosaccharide by detecting the ions
      responsible for the cleavage of the glycosidic bonds. The detection limits of the
      PA-oligosaccharides by HPLC, MALDI-TOF mass spectrometry, and PSD MALDI-TOF mass
      spectrometry were 20 fmol, 20 fmol, and 2 pmol, respectively. These results
      suggest that a system including HPLC and MALDI-TOF mass spectrometry or HPLC and
      PSD MALDI-TOF mass spectrometry is quite useful for the structural
      characterization of sub-pmol or pmol levels of fucose-containing
      oligosaccharides, and that these methods could be used for the analysis of
      various types of oligosaccharides derived from glycoproteins and
      glycosphingolipids.

PMID- 11308024
TI  - Anencephaly: structural characterization of gangliosides in defined brain
      regions.
AB  - Gangliosides from histopathologically-defined human cerebrum-resembling remnant
      and cerebellum from 37 and 30 gestational week-old anencephaluses were identified
      using mass spectrometry and high performance thin layer chromatography combined
      with immunochemical analysis in comparison to respective normal newborn/fetal and
      adult brain regions. A novel strategy of nano-electrospray ionization quadrupole
      time-of-flight tandem MS has been developed for identification of ganglioside
      components in complex mixtures. By morphoanatomical and histological
      investigation the anencephalic cerebral remnant was found to be aberrant, while
      the anencephalic cerebellum was defined as normal. Total ganglioside
      concentrations in the anencephalic cerebral remnant and the cerebellum were 34%
      and 13% lower in relation to the age-matched controls. In the cerebral remnant,
      GD3, GM2 and GT1b were elevated, while GD1a was decreased in the anencephalic
      cerebral remnant, but enriched in anencephalic cerebellum. GQ1b was reduced in
      both anencephalic regions. Gg4Cer, GM1b and GD1alpha, members of the alpha-series
      biosynthetic pathway, and neolacto-series gangliosides were found to be present
      in anencephalic, as well as in normal, fetal and adult brain tissues, indicating
      the occurrence of these biosynthetic pathways in human brain. In both cerebral
      and cerebellar anencephalic tissues, GM1b, GD1alpha, nLM1 and nLD1 were expressed
      at a higher rate in relation to normal tissue. It can be demonstrated that the
      anencephalic cerebral remnant, as a primitive brain structure, represents a
      naturally-occurring model to study the ganglioside involvement in induction of
      aberrant brain development.

PMID- 11308025
TI  - Acidic glycerol lipids of Trichomonas vaginalis and Tritrichomonas foetus.
AB  - The isolation and characterization of acidic lipids from both Trichomonas
      vaginalis and Tritrichomonas foetus have been carried out using radiolabeling, a
      combination of high performance liquid and thin layer chromatographic techniques,
      and mass spectrometry. Unique among the eukaryotes, these organisms produce
      phosphatidylglycerols and O-acyl phosphatidylglycerol-like compounds. In this
      study, the molecular weight distributions of the phosphatidylglycerols and acyl
      phosphatidylglycerols were determined by negative-ion liquid secondary ionization
      mass spectrometry (LSIMS) and the fatty acyl groups within each molecular species
      were assessed by collision-induced decomposition tandem mass spectrometry (CID
      MS/MS). Both species were found to contain primarily oleic acid in the sn-2
      position. The lipids of T. vaginalis had approximately equal amounts of C16 and
      C18 in the sn-1 position, with varying degrees of unsaturation, especially in the
      C18 species. The T. foetus lipids had C18 almost exclusively, but also varied in
      the unsaturation. Other acidic lipids included inositol phosphosphingolipids and
      inositol diphosphosphingolipids.

PMID- 11308026
TI  - Stimulation of acid sphingomyelinase activity by lysosomal lipids and
      sphingolipid activator proteins.
AB  - Acid sphingomyelinase is a water-soluble, lysosomal glycoprotein that catalyzes
      the degradation of membrane-bound sphingomyelin into phosphorylcholine and
      ceramide. Sphingomyelin itself is an important component of the extracellular
      leaflet of various cellular membranes. The aim of the present investigation was
      to study sphingomyelin hydrolysis as a membrane-bound process. We analyzed the
      degradation of sphingomyelin by recombinant, highly purified acid
      sphingomyelinase in a detergent-free, liposomal assay system. In order to mimic
      the in vivo intralysosomal conditions as closely as possible a number of
      negatively charged, lysosomally occuring lipids including
      bis(monoacylglycero)phosphate and phosphatidylinositol were incorporated into
      substrate-carrying liposomes. Dolichol and its phosphate ester dolicholphosphate
      were also included in this study. Bis(monoacylglycero)phosphate and
      phosphatidylinositol were both effective stimulators of sphingomyelin hydrolysis.
      Dolichol and dolicholphosphate also significantly increased sphingomyelin
      hydrolysis. The influence of membrane curvature was investigated by incorporating
      the substrate into small (SUVs) and large unilamellar vesicles (LUVs) with
      varying mean diameter. Degradation rates were substantially higher in SUVs than
      in LUVs. Surface plasmon resonance experiments demonstrated that acid
      sphingomyelinase binds strongly to lipid bilayers. This interaction is
      significantly enhanced by anionic lipids such as bis(monoacylglycero)phosphate.
      Under detergent-free conditions only the sphingolipid activator protein SAP-C had
      a pronounced influence on sphingomyelin degradation in both neutral and
      negatively charged liposomes, catalyzed by highly purified acid sphingomyelinase,
      while SAP-A, -B and -D had no noticeable effect on sphingomyelin degradation.

PMID- 11308027
TI  - Biosynthesis of N-acetylneuraminic acid in cells lacking UDP-N-acetylglucosamine
      2-epimerase/N-acetylmannosamine kinase.
AB  - The first two steps in mammalian biosynthesis of N-acetylneuraminic acid, an
      important carbohydrate moiety in biological recognition systems, are performed by
      the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine
      kinase. A subclone of the human B lymphoma cell line BJA-B K20, lacking UDP-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine kinase mRNA as well as
      epimerase activity, displayed hyposialylated, functionally impaired cell surface
      glycoconjugates. Here we show that this cell line surprisingly still retains N
      acetylmannosamine kinase activity. A gel filtration analysis of BJA-B K88 control
      cells, which express UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine
      kinase, revealed two N-acetylmannosamine kinase activity peaks, one co-eluting
      with UDP-N-acetylglucosamine 2-epimerase activity and one co-eluting with N
      acetylglucosamine kinase. For this enzyme previous studies already showed a
      ManNAc kinase activity in vitro. In contrast, the hyposialylated BJA-B K20
      subclone displayed only the N-acetylmannosamine kinase peak, co-migrating with N
      acetylglucosamine kinase. The CMP-N-acetylneuraminic acid content of both K88 and
      K20 cells and the sialylation of cell surface glycoconjugates of K20 cells could
      be significantly increased by supplementing the medium with N-acetylmannosamine.
      This N-acetylmannosamine-induced increase was drastically reduced by co
      supplementation with N-acetylglucosamine only in K20 cells. We therefore propose
      the phosphorylation of N-acetylmannosamine as a hitherto unrecognized role of N
      acetylglucosamine kinase in living cells.

PMID- 11308028
TI  - Synthesis of nucleotide-activated oligosaccharides by beta-galactosidase from
      Bacillus circulans.
AB  - The enzymatic access to nucleotide-activated oligosaccharides by a glycosidase
      catalyzed transglycosylation reaction was explored. The nucleotide sugars UDP
      GlcNAc and UDP-Glc were tested as acceptor substrates for beta-galactosidase from
      Bacillus circulans using lactose as donor substrate. The UDP-disaccharides
      Gal(beta1-4)GlcNAc(alpha1-UDP) (UDP-LacNAc) and Gal(beta1-4)Glc(alpha1-UDP) (UDP
      Lac) and the UDP-trisaccharides Gal(beta1-4)Gal(beta1-4)GlcNAc(alpha1-UDP and
      Gal(beta1-4)Gal(beta1-4)Glc(alpha1-UDP) were formed stereo- and regioselectively.
      Their chemical structures were characterized by 1H and 13C NMR spectroscopy and
      fast atom bombardment mass spectrometry. The synthesis in frozen solution at -5
      degrees C instead of 30 degrees C gave significantly higher product yields with
      respect to the acceptor substrates. This was due to a remarkably higher product
      stability in the small liquid phase of the frozen reaction mixture. Under
      optimized conditions, at -5 degrees C and pH 4.5 with 500 mM lactose and 100 mM
      UDP-GlcNAc, an overall yield of 8.2% (81.8 micromol, 62.8 mg with 100% purity)
      for Gal(beta1-4)GlcNAc(alpha1-UDP) and 3.6% (36.1 micromol, 35 mg with 96%
      purity) for Gal(beta1-4)Gal(beta1-4)GlcNAc(alpha1-UDP) was obtained. UDP-Glc as
      acceptor gave an overall yield of 5.0% (41.3 micromol, 32.3 mg with 93% purity)
      for Gal(beta1-4)Glc(alpha1-UDP) and 1.6% (13.0 micromol, 12.2 mg with 95% purity)
      for Gal(beta1-4)Gal(beta1-4)Glc(alpha1-UDP). The analysis of other nucleotide
      sugars revealed UDP-Gal, UDP-GalNAc, UDP-Xyl and dTDP-, CDP-, ADP- and GDP-Glc as
      further acceptor substrates for beta-galactosidase from Bacillus circulans.

PMID- 11308029
TI  - Elucidation of the role of functional amino acid residues of the small sialidase
      from Clostridium perfringens by site-directed mutagenesis.
AB  - Bacterial sialidases represent important colonization or virulence factors. The
      development of a rational basis for the design of antimicrobials targeted to
      sialidases requires the knowledge of the exact roles of their conserved amino
      acids. A recombinant enzyme of the 'small' (43 kDa) sialidase of Clostridium
      perfringens was used as a model in our study. Several conserved amino acids,
      identified by alignment of known sialidase sequences, were altered by site
      directed mutagenesis. All recombinant enzymes were affinity-purified and the
      enzymatic characteristics were determined. Among the mutated enzymes with
      modifications in the environment of the 4-hydroxyl group of bound sialic acids,
      D54N and D54E exhibited minor changes in substrate binding. However, a reduced
      activity and changes in their pH curves indicate the importance of a charged
      group at this area. R56K, which is supposed to bind directly to sialic acids as
      in the homologous Salmonella typhimurium sialidase, showed a 2500-fold reduced
      activity. The amino acids Asp-62 and Asp-100 are probably involved in catalysis,
      indicated by reduced activities and altered temperature and pH curves of mutant
      enzymes. Exchanging Glu-230 with threonine or aspartic acid led to dramatic
      decreases in activity. This residue and Y347 are supposed to be crucial for
      providing a suitable environment for catalysis. However, unaltered pH curves of
      mutant sialidases exclude their direct involvement in protonation or
      deprotonation events. These results indicate that the interactions with the
      substrates vary in different sialidases and that they might be more complex than
      suggested by mere static X-ray structures.

PMID- 11308030
TI  - Biosynthesis of lipid-linked oligosaccharides in yeast: the ALG3 gene encodes the
      Dol-P-Man:Man5GlcNAc2-PP-Dol mannosyltransferase.
AB  - The formation of N-glycosidic linkages of glycoproteins involves the ordered
      assembly of the common Glc3Man9GlcNAc2 core-oligosaccharide on the lipid carrier
      dolichyl pyrophosphate. Whereas early mannosylation steps occur on the
      cytoplasmic side of the endoplasmic reticulum with GDP-Man as donor, the final
      reactions from Man5GlcNAc2-PP-Dol to Man9GlcNAc2-PP-Dol on the lumenal side use
      Dol-P-Man. We have investigated these later stages in vitro using a detergent
      solubilized enzyme extract from yeast membranes. Mannosyltransfer from Dol-P-Man
      to [3H]Man5GlcNAc2-PP-Dol with formation of all intermediates up to Man9GlcNAc2
      PP-Dol occured in a rapid, time- and protein-dependent fashion. We find that the
      initial reaction from Man5GlcNAc2-PP-Dol to Man6GlcNAc2-PP-Dol is independent of
      metal ions, but further elongations need Mn2+ that can be partly replaced by Mg2+
      or Ca2+. Zn2+ or Cd2+ ions were found to inhibit formation of Man(7-9)GlcNAc2-PP
      Dol, but do not affect synthesis of Man6GlcNAc2-PP-Dol. Extension did not occur
      when the acceptor was added as a free Man5GlcNAc2 oligosaccharide or when GDP-Man
      was used as mannosyl donor. The alg3 mutant was described to accumulate
      Man5GlcNAc2-PP-Dol. We expressed a functional active HA-epitope tagged ALG3
      fusion and succeeded to selectively immunoprecipitate the Dol-P-Man:Man5GlcNAc2
      PP-Dol mannosyltransferase activity from the other enzymes of the detergent
      extract involved in the subsequent mannosylation reactions. This demonstrates
      that Alg3p represents the mannosyltransferase itself and not an accessory protein
      involved in the reaction.

PMID- 11308031
TI  - Intra- and intermolecular triplex DNA formation in the murine c-myb proto
      oncogene promoter are inhibited by mithramycin.
AB  - Mithramycin inhibits transcription by binding to G/C-rich sequences, thereby
      preventing regulatory protein binding. However, it is also possible that
      mithramycin inhibits gene expression by preventing intramolecular triplex DNA
      assembly. We tested this hypothesis using the DNA triplex adopted by the murine c
      myb proto-oncogene. The 5'-regulatory region of c-myb contains two
      polypurine:polypyrimidine tracts with imperfect mirror symmetry, which are highly
      conserved in the murine and human c-myb sequences. The DNA binding drugs
      mithramycin and distamycin bind to one of these regions as determined by DNase I
      protection assay. Gel mobility shift assays, nuclease and chemical
      hypersensitivity and 2D-gel topological analyses as well as triplex-specific
      antibody binding studies confirmed the formation of purine*purine:pyrimidine
      inter- and pyrimidine*purine:pyrimidine intra-molecular triplex structures in
      this sequence. Mithramycin binding within the triplex target site displaces the
      major groove-bound oligonucleotide, and also abrogates the supercoil-dependent H
      DNA formation, whereas distamycin binding had no such effects. Molecular modeling
      studies further support these observations. Triplex-specific antibody staining of
      cells pretreated with mithramycin demonstrates a reversal of chromosomal triplex
      structures compared to the non-treated and distamycin-treated cells. These
      observations suggest that DNA minor groove-binding drugs interfere with gene
      expression by precluding intramolecular triplex formation, as well as by
      physically preventing regulatory protein binding.

PMID- 11308032
TI  - Experimental regulation of STAT gene expression reveals an involvement of STAT5
      in interleukin-4-driven cell proliferation.
AB  - The precise roles of signal transducers and activators of transcription (STATs)
      in cytokine-triggered control of cell physiology are not sufficiently well
      understood. We have established cell lines in which the individual functional
      contributions of STAT6 and STAT5a/b to interleukin-(IL-) 3 and -4-dependent
      processes can be readily studied. Mutants of STAT6, STAT5a and 5b lacking the
      transcriptional transactivation domain were fused to the green fluorescent
      protein (GFP) and expressed in the murine pro-B cell line Ba/F3 in a regulatable
      fashion. The expression of these truncated STAT variants could be tightly
      controlled over a wide range by doxycycline in the medium. They specifically
      bound to cognate DNA elements upon cytokine stimulation and acted dominant
      negatively on the transcription of respective reporter genes in response to IL-3
      and -4. The system was applied to the question of STAT contributions to cytokine
      dependent cell proliferation. Expression of dominant-negative STAT6 had no
      significant effect on cell growth in response to both IL-3 and IL-4. In contrast,
      truncated STAT5 interfered with cell proliferation in response to IL-3, and,
      interestingly, also to IL-4. The results support our earlier findings on a role
      of STAT5 in IL-4-induced intracellular signaling and indicate that STAT5b in
      particular is involved in IL-4 receptor-triggered control of cell proliferation.

PMID- 11308033
TI  - Depression in the medically ill: a common and serious disorder.

PMID- 11308034
TI  - Comparative strength of association between religious attendance and survival.
AB  - OBJECTIVE: Analyze effects on long-term survival of frequent religious attendance
      compared with four widely-accepted beneficial health behaviors. METHOD: Calculate
      gender-specific associations with mortality over 29 years for religious
      attendance, cigarette smoking, physical activity, alcohol consumption, and non
      religious social involvement. Subjects were 5,894 participants in the Alameda
      County Study age 21-75. Analyses use proportional hazards modeling with time
      dependent measures to adjust for subsequent changes in attendance and each health
      behavior over the follow-up period. All statistical models adjust for the same
      variables. RESULTS: For women, the protective effect of weekly religious
      attendance was of the same order of magnitude as the four other health behaviors.
      For men, the protective effect of weekly religious attendance was less than for
      any of the other health behaviors. CONCLUSIONS: The protective effect of
      religious attendance for women is comparable to those observed for several
      commonly recommended health behaviors: for men the protective effect of religious
      attendance is more modest. This strong gender difference may be a key to
      understanding how religious attendance exerts its effects.

PMID- 11308035
TI  - Major depression and quality of life in individuals with multiple sclerosis.
AB  - OBJECTIVE: To compare the Quality of Life (QOL) of multiple sclerosis (MS)
      patients with and without lifetime major depression. METHOD: Data on 136 MS
      subjects sampled from the University of Calgary MS Clinic were collected. The
      WHO's Composite International Diagnostic Interview (CIDI) was used to diagnose
      lifetime major depression. The MSQOL-54 was administered to evaluate QOL of the
      subjects. RESULTS: Thirty one (22.8 percent) of the 136 MS subjects had lifetime
      major depression, However, only 6 of these had a current episode at the time of
      data collection. MS patients with lifetime major depression had significantly
      lower MSQOL-54 scores in the QOL domains of Energy, Mental Health, Cognitive
      Function, General Quality of Life, Sexual Function, and Role Limitation-Emotional
      than the MS patients without lifetime major depression. CONCLUSIONS: Lifetime
      major depression may have a substantial impact on the QOL of people with MS.
      Alternatively, MS patients with poor QOL may be at greater risk of major
      depression.

PMID- 11308036
TI  - Psychiatric diagnoses in inner city outpatients with moderate to severe asthma.
AB  - OBJECTIVE: Psychiatric symptoms may be associated with increased asthma morbidity
      and mortality. However, no investigations have identified syndromal psychiatric
      diagnoses in asthma patients using current diagnostic criteria or examined
      treatment received for mental illness. METHOD: We conducted structured clinical
      interviews on 32 patients with moderate to severe asthma to identify current and
      past psychiatric illness. RESULTS: Twenty-five percent of subjects had current
      major depressive disorder, but only 25 percent of these received antidepressants.
      Anxiety disorders, including panic disorder (16 percent), and social (13 percent)
      and specific phobias (28 percent) were also common. All subjects with panic
      disorder were receiving appropriate therapy. CONCLUSIONS: Asthma patients with
      moderate to severe asthma treated at community health facilities may have high
      rates of often untreated mood and anxiety disorders. Interventions aimed at
      identifying and treating psychiatric disorders in this population are needed.

PMID- 11308037
TI  - Hypochondriasis: the patient's perspective.
AB  - OBJECTIVE: The purpose of this investigation was to learn how patients with
      hypochondriasis view their physicians and medical care. METHOD: To accomplish
      this, we identified 20 patients with DSM-III-R hypochondriasis and 26
      nonhypochondriacal patients from a general medicine clinic. Using a
      semistructured interview, we obtained information from patients about their
      recent health problems and medical care. The investigators then reviewed
      transcribed interviews and assigned comments to a series of categories. RESULTS:
      Hypochondriacal and non-hypochondriacal patients made equal numbers of positive
      comments, but hypochondriacal patients made significantly more negative comments
      about physicians' professional characteristics, characteristics of the patients
      themselves and total negative comments. Many viewed physicians they had seen as
      unskilled and uncaring. They indicated that, in many instances, their
      relationships with physicians had suffered from poor communication and
      collaboration. CONCLUSION: Since successful management of patients with
      hypochondriasis rests upon positive relationships, ways must be found to improve
      the frustrating and costly situation that currently exists.

PMID- 11308038
TI  - Counseling for depression by primary care providers.
AB  - OBJECTIVE: Primary care providers (PCPs) deliver a significant amount of
      depression care, yet little is known about the content of clinical encounters
      with depressed patients. We describe the extent to which PCP's encounters with
      depressed and non-depressed patients involve psychotherapeutic counseling
      relative to other types of counseling during primary care visits. METHOD: Cross
      sectional evaluation of audiotaped office visits between October 1997 and
      September 1998 with 154 patients of 27 PCPs at three Veterans' Health
      Administration clinics in California. Using the Roter Interaction Analysis
      System, we coded conversation into mutually exclusive talk categories and
      developed specific measures of depression counseling coded for sequences of
      depression talk. Analysis of variance and covariance was used to evaluate
      differences in counseling by depression type adjusted for encounter length,
      previous depression treatment, patient characteristics, and provider clustering.
      RESULTS: PCPs delivered significantly more depression care (assessed using coded
      audiotapes of patient visits) to their patients with major depression compared
      with patients who had no depression or symptoms but no disorder. However,
      counseling using psychotherapeutic techniques did not differ by depression level
      and was equivalent for patients with major depression and subthreshold relative
      to non-depressed. Encounters with patients who had major depression included more
      talk about depression, devoted more time to discussing depression, and included
      more depression talk per minute. PCP encounters with depressed patients also
      included less biomedical talk compared to other groups. CONCLUSIONS: Findings
      suggest that PCPs do provide depression counseling to their patients who need it
      the most. Whether counseling is associated with appropriate treatment and
      subsequent outcomes will require additional research.

PMID- 11308039
TI  - Panic disorder in primary care: patients' attributions of illness causes and
      willingness to accept psychiatric treatment.
AB  - OBJECTIVE: This study assessed the causes that primary care patients with panic
      disorder (PD) attribute to their panic symptoms, and their acceptance of various
      psychiatric treatment options. METHODS: In a cross-sectional assessment of 306
      patients treated at two primary care clinics, 42 met criteria for DSM-IV PD in
      the past year. The authors classified these 42 PD-positive patients to one of two
      groups: those receiving both primary and specialty mental health care (PC+MH; n =
      19) and those receiving only primary care (PC-only; n = 23). Patients rated the
      probability of four possible causes of their panic symptoms, and level of
      acceptability of three psychiatric and two medical treatments for PD. To place
      primary care patients' ratings into a broader context, a third contrast group of
      PD-positive patients, recruited from clinical trials of investigational PD
      pharmacotherapies (n = 31), also rated causes and treatment acceptability.
      RESULTS: Participants of the three treatment groups attributed psychiatric causes
      for their panic symptoms in approximately the same proportion (78 percent to 90
      percent; p = ns). PC-only participants attributed medical causes for panic
      symptoms more frequently than PC+MH and PD Clinical Trials participants (48
      percent vs. 5 percent and 32 percent; p = .01). Remarkably, the great majority of
      patients across all groups expressed willingness to see psychiatrists (84 percent
      to 94 percent) and psychotherapists (95 percent to 100 percent), and to take
      psychotropic medications (87 percent to 100 percent). CONCLUSIONS: In this study
      most patients attributed a psychiatric cause for panic symptoms and communicated
      strong acceptance of psychiatric treatment. Thus, we recommend that primary care
      clinicians more assertively inform their patients of PD diagnoses and recommend
      psychiatric treatments with less fear about stigmatizing and alienating them.

PMID- 11308040
TI  - Religion and medicine I: historical background and reasons for separation.
AB  - Religion and medicine have a long, intertwined, tumultuous history, going back
      thousands of years. Only within the past 200-300 years (less than 5 percent of
      recorded history) have these twin healing traditions been clearly separate. This
      series on religion and medicine begins with a historical review, proceeding from
      prehistoric times through ancient Egypt, Greece, and early Christianity through
      the Middle Ages, the Renaissance, and the Age of Enlightenment, when the split
      between religion and medicine became final and complete. Among the many reasons
      for the continued separation is that religion may either be simply irrelevant to
      health or, worse, that it may have a number of negative health effects. I review
      here both opinion and research supporting this claim.

PMID- 11308041
TI  - Graves' disease in childhood.
AB  - The vast majority of thyrotoxicosis cases in children are caused by Graves'
      disease (GD) and these account for 10-15% of all childhood thyroid diseases. The
      major clinical features of thyrotoxicosis in children are, in general, similar to
      those in adults. As in adults, the three conventional methods of treatment are
      antithyroid drugs (ATD), thyroidectomy and ablative radioiodine (131I). Although
      ATD are associated with side effects and a high relapse rate even after prolonged
      therapy, they still seem to be chosen as the first line of therapy for GD in
      childhood by most pediatric endocrinologists, although some have started using
      131I as their first therapeutic modality. However, when ATD therapy has to be
      discontinued, or after relapse which may occur during or following ATD therapy, a
      definitive mode of therapy has to be chosen. Since thyroidectomy has the
      disadvantages of hospitalization and surgical complications, there is now an
      increasing tendency to advocate radioiodine as a choice of treatment in children
      older than five years old who achieve a high rate of remission. It should be kept
      in mind that with both thyroidectomy and radioiodine treatment, permanent
      hypothyroidism is very common and requires lifelong replacement therapy.
      According to the long-term follow-up data which have been published, radioiodine
      treatment in older children and adolescents seems to be safe and effective.
      Although studies of children with GD treated with ablative doses of radioiodine
      have not revealed an apparent increased risk of thyroid malignancy, a long-term
      study of larger populations is needed in order to define the true incidence of
      thyroid neoplasia, and other possible side effects, in children treated with
      radioiodine. Although the relatively low risks, low cost and practicability of
      radioiodine treatment has favored this therapy for children, as it has for
      adults, in the United States, it is still less attractive for European
      physicians. Progress in the immunological understanding of GD and of its genetic
      background will hopefully elucidate the pathways leading to GD, as well as the
      factors determining who is at high risk of developing GD, and may thus ultimately
      promote novel strategies for a more successful and safe therapy.

PMID- 11308042
TI  - New thoughts on female precocious puberty.
AB  - Much effort has been devoted in recent years to unravel the neuroendocrine
      mechanisms responsible for the initiation of mammalian puberty. The concept that
      has emerged is that puberty results from the unfolding of a centrally originated
      process involving the concerted influence of neuronal systems that utilize
      excitatory and inhibitory amino acids as transmitters and astroglial networks
      that produce growth factors able to affect LHRH secretion. We discuss the idea
      that an isolated alteration of each of these components may result in the
      precocious activation of pulsatile LHRH release, and thus lead to idiopathic
      sexual precocity. According to this notion, such a premature activation of LHRH
      neuronal function would be neither associated with structural damage of the
      neuroendocrine brain system, nor related to a generalized activation of the
      neuronal-glial mechanisms underlying the onset of puberty. On the contrary,
      localized activation of discrete cellular subsets functionally connected to LHRH
      neurons would suffice to promote an increase in LHRH release of sufficient
      magnitude and duration to initiate the pubertal process.

PMID- 11308043
TI  - The relationship between ovarian structure and hyperandrogenism in premature
      pubarche.
AB  - The aim of this study was to describe the ovarian structure (OS) and its
      relationship with hyperandrogenism in girls with premature pubarche (PP). A
      pelvic ultrasound was carried out in 23 girls with PP and in 57 prepubertal age
      matched controls (C), and the OS was subdivided into five classes (c): 1
      homogeneous; 2-microcystic, 3-multicystic, 4-polycystic and 5-follicular. In the
      girls with PP, an ACTH test was performed, and the presence of hormonal levels >3
      SD of postpubertal normal levels and not compatible with late-onset congenital
      adrenal hyperplasia were considered an exaggerated response. The fasting levels
      of glucose (G) and insulin (I) were measured and the fasting I to G ratio (FIGR)
      was calculated. FIGR >22 was suggestive of I resistance (IR). The microcystic
      structure (c2) was more frequently found in the PP than in the C group (63% vs
      35%, p=0.03). In the PP group, we observed the following OS: cl (n=6), c2 (n=15),
      c3 (n=1) and c4 (n=1). 11-Deoxycortisol--both basal and after ACTH--was greater
      in the PPc2 group than in PPc1 (p=0.04, p=0.0008, respectively). We also observed
      an exaggerated response to ACTH in 87% of the girls with PP, greater in the PPc2
      group than in PPc1 (p=0.04). The FIGR showed IR in 44% of girls with PP, but I
      levels and FIGR were similar between PPc1 and PPc2. These findings suggest
      generalized adrenocortical hyperresponsiveness in girls with PP, which is more
      accentuated in PPc2. Long-term follow-up of girls with PP into adulthood is
      warranted to ascertain whether microcystic ovarian structure precedes functional
      ovarian hyperandrogenism.

PMID- 11308044
TI  - Improvement of HbA1c without increased hypoglycemia in adolescents and young
      adults with type 1 diabetes mellitus treated with recombinant human insulin-like
      growth factor-I and insulin. rhIGF-I in IDDM Study Group.
AB  - OBJECTIVE: A 12-week trial with insulin and rhIGF-I compared to insulin and
      placebo was conducted in patients with type 1 diabetes mellitus aged 11-66 years.
      We present the efficacy and safety data pertinent to the younger subset of
      participants (11-21 years). STUDY DESIGN: The patients were randomized to receive
      s.c. insulin and either placebo or rhIGF-I at one of the following doses
      (microg/kg): 40 a.m./40 p.m., 80 a.m./40 p.m. or 80 a.m./60 p.m.). RESULTS: The
      average decrease of HbA1c from baseline was higher (-1.3 +/- 0.2%) in the rhIGF-I
      treated group compared to the placebo group (-0.6 +/- 0.3%; p <0.05). This was
      associated with a significant decrease in daily insulin dose (U) of both Regular
      (rhIGF-I: -7 +/- 1; placebo: -1 +/- 1; p <0.01) and NPH (rhIGF-I: -4 +/- 2;
      placebo: +5 +/- 3; p <0.05). The incidence of hypoglycemia and weight gain were
      not increased. Edema, jaw pain and tachycardia were associated with rhIGF-I
      treatment, particularly at doses higher than 40 microg/kg b.i.d. Dose-related
      early worsening of retinopathy was observed in 11/55 patients in the rhIGF-I
      group, with resolution in the majority of them in the follow-up photographs.
      CONCLUSIONS: These findings suggest a possible role for rhIGF-I co-therapy in
      adolescents and young adults with type 1 diabetes mellitus.

PMID- 11308045
TI  - Autoimmune thyroid disease in Indian children with type 1 diabetes mellitus.
AB  - The objective of the present study was to determine the prevalence of autoimmune
      thyroid disease in Indian children with type 1 diabetes mellitus by the assay of
      antibodies to thyroid peroxidase and thyroglobulin. The study population
      consisted of 35 children with type 1 diabetes mellitus and 32 healthy age- and
      sex-matched control children. Thyroid peroxidase antibodies (TPO) were determined
      by ELISA and thyroglobulin antibodies (TGA) by passive hemagglutination. Thyroid
      function tests and tests of glycemic control were also performed. These assays
      were repeated after six months and one year. TPO were observed in 19 (54.3%)
      patients compared to three (10%) controls, and TGA in 11 (31.4%) patients and
      none of the controls. Both these observations were statistically significant with
      p=0.0002 for TPO and 0.0016 for TGA. The prevalence of these antibodies was not
      different in boys and girls and did not change with the duration of diabetes. All
      patients who were positive for TGA were also positive for TPO. Thyroid function
      tests were abnormal in one patient who was found to have Hashimoto's thyroiditis.
      There is a definite need to screen all diabetic children for thyroid antibodies
      and carefully follow up those patients in whom these antibodies are positive.

PMID- 11308046
TI  - Serum soluble endothelial-cell specific adhesion molecules in children with
      insulin-dependent diabetes mellitus.
AB  - Endothelial-cell specific adhesion molecules are reported to be elevated in
      patients with diabetes mellitus and related to diabetic vascular complications.
      We studied serum concentrations of soluble intercellular adhesion molecule-1
      (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), endothelial-leukocyte
      adhesion molecule (sE-selectin) in 30 healthy children and 35 children with type
      1 diabetes without symptomatic vascular complications. sE-selectin levels were
      higher in diabetics than in controls (p < 0.001). sVCAM-1 and sICAM-1 levels were
      not different between the groups (p > 0.05). In seven newly diagnosed diabetics
      with ketoacidosis, concentrations of these molecules were not different before
      and after one month of insulin therapy (p > 0.05). In the combined group, only sE
      selectin was correlated positively with serum glucose, HbA1c (r = 0.3, p < 0.05
      for both) and negatively with C-peptide levels (r = -0.4, p < 0.05). In diabetic
      children without symptomatic vascular complications, sE-selectin but not sICAM
      and sVCAM levels was elevated; this finding might reflect ongoing endothelial
      cell activation rather than endothelial damage.

PMID- 11308047
TI  - Molecular analysis of hereditary hyperferritinemia-cataract syndrome in a large
      Basque family.
AB  - Hereditary hyperferritinemia-cataract syndrome is a genetic condition
      characterized by constitutively increased serum ferritin values in the absence of
      iron overload and by bilateral cataract. It has been demonstrated that mutations
      in the stem loop structure of the iron regulatory element (IRE) located in the 5'
      untranslated region of the ferritin L-subunit gene (19q13.1) are responsible for
      the anomalous expression of this protein. Although not clearly explained,
      cataract formation seems secondary to the increased levels of ferritin in the
      lens. We analyzed a large Basque family in order to identify possible germline
      alterations of the iron regulatory element of the ferritin-L gene in affected
      individuals and first-degree relatives. All members of the family presented
      hyperferritinemia and cataract except a young child who had hyperferritinemia but
      did not present cataract. Sequence analysis permitted the identification of an
      A40-->G mutation in all members, including this child. This could demonstrate
      that cataract formation is a consequence of ferritin accumulation in the lens.

PMID- 11308048
TI  - Evaluation of gonadotrophin insufficiency in thalassemic boys with pubertal
      failure: spontaneous versus provocative test.
AB  - The objective of this study was to determine whether iron toxicity in blood
      transfusion dependent beta-thalassemic patients with pubertal failure was
      associated with gonadotrophin (GTH) insufficiency as assessed by spontaneous and
      dynamic tests. Gonadotrophin-releasing-hormone (GnRH)-GTH secretory dynamics were
      studied by serial ultradian GTH profiles and a 100 microg i.v. GnRH bolus test
      (GBT) in 28 male beta-thalassemia major patients with failed puberty (FP group).
      Five healthy, non thalassemic prepubertal males were studied for comparative
      purposes. According to the pulse profile, patients in the FP group were
      subdivided into apulsatile (no FSH and LH pulses, n = 16; AFP group) and
      pulsatile (defective pulse profile, n = 12; PFP group) subsets. The FP group had
      lower basal FSH (p < 0.01), LH (p < 0.01) and GnRH stimulated FSH (p < 0.001) and
      LH levels (p < 0.001) than the controls. However, basal and GnRH-stimulated FSH
      (p < 0.01 for basal and p < 0.001 for peak) and LH (p < 0.01 for both basal and
      peak) levels were lower in the AFP than the PFP group. Serum ferritin levels in
      GnRH-non-responders were higher than those in the responders (9,052.63 +/- 579.14
      mg/l vs 5,933.33 +/- 1,819.65 mg/l; p < 0.05). Similarly, symptomatic organ
      damage was higher in the AFP than the PFP patients (81% vs 42%; p < 0.001). In
      conclusion, this study suggests that iron overloaded thalassemic patients with
      failed puberty had abnormal GnRH-GTH secretory dynamics. The severity of the
      defect was heterogeneous, ranging from very severe (apulsatile) to less severe
      (pulsatile) subsets. Comparison between spontaneous and dynamic test levels
      showed that there was concordance between the degree of pulse defect and
      magnitude of LH response to GBT. However, ultradian GTH profile was a more
      reliable method for identifying the degree of GTH insufficiency than GBT. Our
      data also showed that iron toxicity was the major cause of GnRH-GTH deficiency in
      thalassemic patients. Such information may be useful for better understanding of
      the pathophysiology of hypogonadotrophic hypogonadism (HH), thereby promoting
      therapeutic options for induction of puberty and spermatogenesis.

PMID- 11308049
TI  - Growth hormone treatment in short children with intrauterine growth retardation.
AB  - The aim of this prospective controlled study was to assess the effect of rhGH in
      short prepubertal children with intrauterine growth retardation and normal growth
      hormone status. Twenty-six children were randomized into treatment (12F, 4M) and
      control (6F, 4M) groups. Mean ages were 5.3 (1.3) yr and 4.3 (1.7) yr,
      respectively. rhGH (Genotropin) was used at a dose of 0.2 IU/kg/day as daily s.c.
      injections for two years. In the treated group, mean height SDS increased from 
      3.0 (0.5) to -1.9 (0.7) and height velocity SDS showed a significant increase
      from -1.3 (2.0) to 3.7 (1.8) in the first year (p < 0.001) and 1.6 (1.8) (p <
      0.01) in the second year of treatment. In the controls, height SDS, initially 
      2.7 (1.4), and height velocity SDS, initially -0.9 (1.1), remained essentially
      the same during two years of follow-up. Height SDS for bone age changed by 0.6 in
      the treated group and 0.4 in the control group. Target height SDS--initial height
      SDS in the treated group improved by 1.1 SD but declined in the control group.
      IGF-I levels increased from 9.5 (4.2) nmol/l (72 [31.8] ng/ml) to 32.5 (27.0)
      nmol/l (244.4 [202.8] ng/ml) (p = 0.004) in the treated group while no change was
      observed in the controls. No adverse effects were encountered during rhGH
      therapy. It was concluded that rhGH treatment induces a significant increase in
      growth velocity in the short term. This outcome, as opposed to the unchanged
      indices in the control group over the same period, may be indicative of an
      improved height prognosis in short children born with intrauterine growth
      retardation treated with rhGH.

PMID- 11308050
TI  - Disorders of growth and puberty in children with non-tumoral hydrocephalus.
AB  - Hydrocephalus may cause disorders of growth and puberty. 31 patients (25 girls)
      with non-tumoral hydrocephalus were seen at 8.5 +/- 3.1 (SD) years for short
      stature (8 patients), overweight (8 patients), central early puberty (onset
      before 9 years, 21 patients), premature pubarche (1 patient) and/or delayed
      puberty (2 patients). Among the patients with short stature, 4 had
      meningomyelocele and one had untreated early puberty. Only 1/11 patients
      evaluated had growth hormone deficiency. Among the overweight patients, 5 had
      early puberty. The plasma leptin concentrations were positively correlated with
      the body mass index (r = 0.65, p < 0.01, n = 14). Free thyroxin, cortisol,
      prolactin and concomitant plasma and urinary osmolalities were normal in all
      cases evaluated, except one who had low free thyroxin. The 7 patients with early
      puberty and who were given gonadotropin releasing hormone analog for over 2 years
      had mean predicted adult height of -2.45 +/- 1.9 SD before treatment and -2.46 +/
      1.4 SD afterwards. Ventriculocisternostomy performed on 2 girls seen for delayed
      puberty was followed by breast development and menarche. In conclusion, in
      children with hydrocephalus, short stature is frequently due to meningomyelocele
      and rarely to GH deficiency. Central early puberty is the most frequent endocrine
      disorder.

PMID- 11308051
TI  - Rickets as an unusual initial presentation of abetalipoproteinemia and
      hypobetalipoproteinemia.
AB  - OBJECTIVE: Description of rickets as an unexpected initial manifestation in two
      children with abetalipoproteinemia and hypobetalipoproteinemia, and elucidation
      of its pathophysiology in these conditions. METHODOLOGY: Two infants aged two and
      six months with abetalipoproteinemia and hypobetalipoproteinemia respectively had
      clinical rickets at presentation, confirmed radiologically and biochemically.
      Vitamin D intake and serum levels were measured and other causes of rickets were
      looked for. RESULTS: Vitamin D intake and laboratory studies levels were
      suggestive of rickets due to calcium deficiency instead of vitamin D deficiency.
      Healing of rickets occurred with dietary treatment of the malabsorption, without
      any dietary calcium or significant vitamin D supplementation. CONCLUSION:
      Steatorrhea-induced calcium malabsorption seems to be the most likely cause of
      rickets in this entity.

PMID- 11308052
TI  - Fatal liver failure due to ketoconazole treatment of a girl with Cushing's
      syndrome.
AB  - A patient is reported who developed fatal liver failure on ketoconazole treatment
      for Cushing's syndrome. It is recommended that metyrapone be used when
      hypercortisolism has to be controlled as a temporary measure in childhood and
      adolescence.

PMID- 11308053
TI  - The experience of patients with rheumatoid arthritis admitted to hospital.
AB  - OBJECTIVE: To describe the experiences of patients with rheumatoid arthritis (RA)
      when admitted to hospital. METHODS: A selected sample of 9 women with RA of at
      least 3 years duration, who had experienced at least 5 days of inpatient care
      within the previous 2 years, underwent unstructured interviews in this
      qualitative, phenomenological study. Information from the interviews was analyzed
      using Colaizzi's 6 procedural steps. RESULTS: Five major themes emerged from the
      study: uncertainty during the first admission to hospital; the process of
      becoming an experienced patient on subsequent admissions; the evident experience
      and knowledge of staff; the effect, both positive and negative, of other
      patients; and the loss of privacy. CONCLUSION: These findings throw important new
      light on the experience of patients with RA receiving inpatient rheumatologic
      care and have the potential to significantly advance nursing practice within
      rheumatology.

PMID- 11308054
TI  - Physiology of cytokine pathways in rheumatoid arthritis.
AB  - This review has summarized the physiology of some cytokine pathways in RA,
      emphasizing the redundant and synergistic nature of this network. However, it is
      important to understand that this system is self-regulating through the action of
      anti-inflammatory cytokines, opposing cytokines, cytokine receptor antagonists,
      and possibly naturally occurring antibodies to cytokines (Figure 1). Disease
      results when an imbalance in the cytokine network develops, either from excess
      production of pro-inflammatory cytokines or from inadequate presence of natural
      anti-inflammatory mechanisms. The current therapeutic approaches to RA that are
      aimed at restoring this balance include the use of monoclonal antibodies to
      TNFalpha, soluble TNFalpha receptors, and IL-1Ra. Other therapeutic agents that
      interfere with the cytokine network are in various stages of preclinical and
      clinical evaluation.

PMID- 11308055
TI  - Glucosamine and chondroitin for osteoarthritis.

PMID- 11308056
TI  - On the history of eponymic idiopathic vasculitis: comment on the article by
      Matteson.

PMID- 11308057
TI  - Rhemulatologists' performance in dailiy practice.
AB  - OBJECTIVE: To assess rheumatologists' performance for 8 rheumatologic conditions
      and to explore possible explanatory factors. METHODS: After written informed
      consent was obtained, 27 rheumatologists (21% of all Dutch rheumatologists)
      practicing in 16 outpatient departments were each visited by 8 incognito
      "standardized patients" (SPs). The diagnoses of these 8 cases account for about
      23% of all new referred patients in the Netherlands. Results for ordered lab
      tests as well as real radiographs with corresponding results from a radiologist
      were simulated. Information from the visits was obtained from the SPs, who
      completed predefined case-specific checklists, and by collecting data on resource
      utilization. Feedback was provided. RESULTS: Altogether 254 encounters took
      place, of which 201 were first visits and 53 were followup visits. SPs were
      unmasked twice during a visit. There was considerable variation in resource
      utilization (lab tests and imaging) between cases and between rheumatologists.
      Mean costs per rheumatologist ranged from US $ 4.67 to $ 65.36 per visit for lab
      tests and from US $ 33.15 to $ 226.84 per visit for imaging tests. No significant
      correlations were seen between resource utilization costs and number of years of
      clinical experience or performance on checklist scores. Rheumatologists with
      longer experience had lower total item checklist scores (r = -0.47; P < 0.05).
      CONCLUSION: A considerable variation in resource utilization was found among 27
      Dutch rheumatologists. The information obtained is an excellent source for
      discussion on the appropriateness of care.

PMID- 11308058
TI  - The need for comprehensive educational osteoporosis prevention programs for young
      women: results from a second osteoporosis prevention survey.
AB  - OBJECTIVE: To assess osteoporosis knowledge, beliefs, and preventive behaviors
      among young adult women and to identify sources that they would mostly likely
      utilize to learn more about the disease. METHODS: Information was gathered
      through a cross-sectional survey of 321 women (mean age 21.6 years; 63.5% were
      white, 29.2% were black) enrolled in a required undergraduate health course at a
      southeastern state university. RESULTS: Two hundred seventy-seven (86%) of the
      survey participants had heard about osteoporosis, but only 3.8% of respondents
      reported getting both adequate exercise and the recommended 1,200 mg of calcium
      per day. Respondents believed that they were unlikely to develop osteoporosis and
      that osteoporosis is less serious than other common causes of morbidity and
      mortality in women, such as heart disease and breast cancer (P < 0.0001).
      Brochures, magazines, and short counseling sessions were preferred information
      sources for learning about osteoporosis. CONCLUSIONS. The majority of young women
      studied are at risk for developing premature osteoporosis. They prefer brochures,
      magazines, and short counseling sessions during medical office visits to learn
      about osteoporosis.

PMID- 11308059
TI  - Kinematic approach to gait analysis in patients with rheumatoid arthritis
      involving the knee joint.
AB  - OBJECTIVE: To analyze abnormal gait patterns in patients with rheumatoid
      arthritis involving the knee joint. METHODS: In 2 patient groups with rheumatoid
      arthritis, changes in relevant angular parameters in the sagittal plane were
      analyzed by an electromagnetic tracking instrument. One group consisted of
      patients with knee joint involvement and severe inflammation without progressive
      destruction; the other group had knee joint involvement with progressive
      destruction and low disease activity. Knee angle was measured as the projected
      angle in the sagittal plane formed by 3 sensors (hip-knee-ankle); the changing
      mean angle, angular velocity, and angular acceleration were displayed.
      Furthermore, the angle formed by the vector element's endpoints for each sensor's
      displacement (designated alpha angle) was measured continuously. RESULTS:
      Compared with age-matched controls, patients with severe inflammatory knee joint
      involvement showed limitation of alpha angle change in the stance phase, and
      patients with knee joint destruction had shortened swing phase duration and
      decreased alpha angle change in the swing phase. A sharpened alpha angular
      velocity change curve was observed in the latter. Characteristic differences
      between groups with inflammation and destruction were more clearly evident from
      the alpha angle than from the knee angle itself. CONCLUSION: We observed gait
      differences between rheumatoid arthritis patients with active inflammatory
      arthritic knee joint involvement without progressive destruction and those with
      joint destruction and minimal inflammation. Features of gait disturbance in
      rheumatoid arthritis were not simple, even with a single major site. Therefore,
      techniques such as biokinetic gait analysis can provide practical information
      about functional joint integrity in this patient population that could aid in
      therapeutic decision making.

PMID- 11308060
TI  - Effects of pool-based and land-based aerobic exercise on women with
      fibromyalgia/chronic widespread muscle pain.
AB  - OBJECTIVE: To examine the effects of pool-based (PE) and land-based (LE) exercise
      programs on patients with fibromyalgia. METHODS: The outcomes were assessed by
      the Fibromyalgia Impact Questionnaire, the Arthritis Self-Efficacy Scale, and
      tests of physical capacity. RESULTS: Eighteen subjects in the PE group and 16 in
      the LE group performed a structured exercise program. After 20 weeks, greater
      improvement in grip strength was seen in the LE group compared with the PE group
      (P < 0.05). Statistically significant improvements were seen in both groups in
      cardiovascular capacity, walking time, and daytime fatigue. In the PE group
      improvements were also found in number of days of feeling good, self-reported
      physical impairment, pain, anxiety, and depression. The results were mainly
      unchanged at 6 months followup. CONCLUSION: Physical capacity can be increased by
      exercise, even when the exercise is performed in a warm-water pool. PE programs
      may have some additional effects on symptoms.

PMID- 11308061
TI  - Coping strategies, pain, and disability in patients with hemophilia and related
      disorders.
AB  - OBJECTIVE: To analyze the use of various coping strategies in homogeneous groups
      of patients with hemophilia and von Willebrand's disease and to investigate the
      relationship between the state of the disease, the use of coping strategies, and
      management of the disease. METHODS: The coping strategies measured by the Coping
      Strategies Questionnaire were analyzed in 3 homogeneous groups of 224 patients.
      Psychosocial well-being (PWB) measured by the Rand 36-item Health Survey 1.0 was
      used as an indicator of management of the disease. The pain factor consisted of
      the following variables: pain intensity, use of analgesics, Functional Disability
      Index, and physical activity level. RESULTS: The groups of patients differed
      significantly only in the use of the catastrophizing strategy (CAT). In all pain
      groups, distraction was the most commonly used coping strategy. A significant
      interaction effect of pain factor and age on PWB (P = 0.04) was found. The
      mediating function of the CAT strategy was confirmed by the series of regression
      analyses. CONCLUSION: The coping strategy profile in hemophilia was found to be
      similar to those in other chronic pain states. The use of the strategies does not
      depend on the severity of the disease. We confirmed the role of age and the use
      of the CAT strategy as, respectively, moderator and mediator in the pattern of
      relationships between the clinical state of the disease and psychosocial well
      being.

PMID- 11308062
TI  - Responsiveness of observational and self-report methods for assessing disability
      in mobility in patients with osteoarthritis.
AB  - OBJECTIVE: To establish the responsiveness of observational and self-report
      methods for the assessment of disability in mobility in patients with
      osteoarthritis (OA). METHODS: Data from 186 patients with hip OA or knee OA were
      used. Data from 1 observational method and 4 self-report methods for the
      assessment of disability in mobility were collected at week 0 and again 12 weeks
      later. Using correlations and factor analysis, the relationships among changes in
      these 5 methods were established. RESULTS: Intercorrelations between change
      scores of the self-report methods ranged from 0.12 to 0.34. Correlations between
      the observational method and the self-report methods ranged from 0.14 to 0.26. In
      the factor analysis, both the self-report methods and the observational method
      loaded on the same factor. CONCLUSION: In a longitudinal design, no evidence for
      differential responsiveness of observational and self-report methods was
      obtained. Because of the advantages of questionnaires (they are easier to use,
      less time-consuming, and less of a burden to subjects), this implies that the use
      of self-report methods is to be preferred over observational methods.

PMID- 11308063
TI  - The motor dysfunction of patients with knee osteoarthritis in a Chinese
      population.
AB  - OBJECTIVE: To determine the extent of motor dysfunction in people with knee
      osteoarthritis (OA), as compared with similarly aged subjects without knee OA, in
      a Chinese population. METHODS: Seventy-six subjects participated in this study.
      Isometric peak torque of the knee muscles, range of knee motion at rest and
      during walking, gait velocity, cadence, and stride length were compared. RESULTS:
      The isometric peak torque of both the quadriceps and the hamstrings of the
      affected leg of patients with knee OA were weaker than those of the controls
      (most P < 0.05). The gait velocity was 23.4% slower (P = 0.001), the cadence
      33.3% less (P < 0.001), and the stride length 13.4% shorter (P = 0.010) in the
      patients with OA. The range of knee motion in the patients was reduced by 11.2%
      at rest (P = 0.003) and by 14.7% during walking (P = 0.001). CONCLUSION: Patients
      with knee OA exhibited statistically significant deficiencies in the physical
      performance tested, as compared with similarly aged subjects without knee OA (by
      9.6% to 33.3%), in a Chinese population. The indication that this study group
      seems less severely limited than those reported in Western literature warrants
      further investigation.

PMID- 11308064
TI  - Effects of a coping intervention on patients with rheumatic diseases: results of
      a randomized controlled trial.
AB  - OBJECTIVE: To test the effects (on coping, social interactions, loneliness,
      functional health status, and life satisfaction) of an intervention aimed at
      teaching people with rheumatic diseases to cope actively with their problems.
      METHODS: A total of 168 patients with chronic rheumatic disorders affecting the
      joints were randomly assigned to a coping intervention group, a mutual support
      control group, or a waiting list control group. Measurements were by self-report
      questionnaires. RESULTS: Post-intervention measurements showed that the coping
      intervention increased action-directed coping and functional health status, but
      these effects did not persist up to 6-months followup. In patients who attended
      at least half of the 10 sessions, the coping intervention contributed to
      decreased loneliness at post-intervention and to improvements in social
      interactions and life satisfaction at 6-months followup. CONCLUSION: Teaching
      patients with rheumatic diseases to cope actively with their problems had
      positive impacts. Consequently it is recommended that the coping intervention be
      incorporated into regular care. Maintenance sessions are advisable.

PMID- 11308065
TI  - The perils and pitfalls of comparing UK and US samples of people enrolled in an
      Arthritis Self-Management Program: the case of the Center for Epidemiological
      Studies-Depression (CES-D) Scale.

PMID- 11308066
TI  - Involvement and satisfaction: a Norwegian study of health care among 1,024
      patients with rheumatoid arthritis and 1,509 patients with chronic
      noninflammatory musculoskeletal pain.
AB  - OBJECTIVE: To investigate involvement in and satisfaction with health care among
      patients with rheumatoid arthritis (RA) and persons with chronic noninflammatory
      musculoskeletal pain, to identify target areas for improvement. METHODS: Data
      were collected from postal surveys carried out in 1994 in Oslo, Norway, with
      1,542 patients with RA and 10,000 randomly selected adults. Patients with RA and
      persons with noninflammatory musculoskeletal pain were asked 3 questions about
      their involvement with treatment and 1 question about their satisfaction with
      health care. Levels of involvement and of satisfaction were related to
      demographic measures, health status measures, use of health services, and, for
      patients with RA, self-efficacy. RESULTS: Of the respondents with RA (n = 1,024),
      40% scored low on at least 1 question on involvement and 11% reported global
      dissatisfaction. Being young, well educated, physically disabled, in good mental
      health, and self-efficient and having visited a rheumatologist in the last 12
      months were associated with a high level of involvement; being female and having
      a low pain level, good mental health, and high self-efficacy were associated with
      satisfaction with health care. Of persons with noninflammatory musculoskeletal
      pain of more than 5 years duration (n = 1,509), 57% scored low on at least 1
      question on involvement and 27% reported global dissatisfaction. Being well
      educated, having visited a general practitioner in the last 12 months, and having
      ever visited a rheumatologist were associated with a high level of involvement.
      Being older and having a low pain level and good mental health were associated
      with satisfaction. A low score on involvement was a strong independent predictor
      of global dissatisfaction in both groups. CONCLUSION: High education level and
      health service provided by rheumatologists were consistently associated with a
      high level of involvement. Good mental health and high involvement were
      associated with satisfaction with the care received. Efforts to achieve a higher
      level of patient involvement should especially be directed toward patients with
      low education, emotional distress, and a chronic physical disorder.

PMID- 11308067
TI  - Do junvenile idiopathic arthritis patients benefit from an exercise program? A
      pilot study.

PMID- 11308068
TI  - Nonstandard and adjunctive medical therapies for systemic lupus erythematosus.

PMID- 11308069
TI  - Introduction and overview. Statistical methods in genetic epidemiology.
AB  - Common terms used in genetics with multiple meanings are explained and a brief
      overview given of the four major areas of genetic epidemiology--the study of
      familial aggregation, segregation, cosegregation and association. Familial
      aggregation measures the potential for a trait to have a genetic aetiology.
      Segregation analysis uncovers single gene segregation. Cosegregation with genetic
      markers gives rise to linkage, which is used to locate trait genes on the genome.
      Association analysis is used for fine mapping, but rests on the assumption that
      linkage disequilibrium exists.

PMID- 11308070
TI  - Statistical designs for familial aggregation.
AB  - In the past two decades, it has become increasingly clear that genetic factors
      contribute to the aetiology of many common diseases including cancers, coronary
      disease, allergy and psychiatric disorders. While one goal of genetic
      epidemiological studies is to locate susceptibility genes for these complex
      diseases, it is important that strong evidence of familial aggregation be
      established at an early stage of research. In this paper, we discuss several
      study designs useful to address some issues such as (1) detecting familial
      aggregation, (2) testing for gene-environment interaction, (3) identifying
      homogeneous subgroups and (4) measuring magnitude and patterns of familial
      correlations. These designs include the conventional case-control design and the
      family case-control design. For each of these two study designs, we discuss
      analytical strategies as well as their strengths and weaknesses. Throughout,
      several examples from real studies are used for illustrative purposes.

PMID- 11308071
TI  - Family-based association studies.
AB  - Over the past decade, attention has turned from positional cloning of Mendelian
      disease genes to the dissection of complex diseases. Both theoretical and
      empirical studies have shown that traditional linkage studies may be inferior in
      power compared to studies that directly utilize allele status. Case-control
      association studies, as an alternative, are subject to bias due to population
      stratification. As a compromise between linkage studies and case-control studies,
      family-based association designs have received great attention recently due to
      their potentially higher power to identify complex disease genes and their
      robustness in the presence of population substructure. In this review, we first
      describe the basic family-based association design involving one affected
      offspring with its two parents, all genotyped for a biallelic genetic marker.
      Extensions of the original transmission disequilibrium tests to multiallelic
      markers, families with multiple siblings, families with incomplete parental
      genotypes, and general pedigree structures are discussed. Further developments of
      statistical methods to study quantitative traits, to analyse genes on the X
      chromosome, to incorporate multiple tightly linked markers, to identify
      imprinting genes, and to detect gene-environment interactions are also reviewed.
      Finally, we discuss the implications of the completion of the Human Genome
      Project and the identification of hundreds of thousands of genetic polymorphisms
      on employing family-based association designs to search for complex disease
      genes.

PMID- 11308072
TI  - Risk models in genetic epidemiology.
AB  - Advances in the identification and treatment of genetically transmitted diseases
      have lead to an increased need for reliable estimates of genetic susceptibility
      risk. These estimates are used in clinic settings to identify individuals at
      increased risk of being a carrier of a disease susceptibility allele as well as
      to define the probability of developing a particular disease given one is a
      carrier. Accurate assessment of these probabilities is extremely important given
      the implications for medical decision making including the identification of
      patients who might benefit from genetic counselling or from entry into clinical
      trials. A wide range of risk models has been proposed including those that
      utilize logistic regression, Cox proportional hazards regression, log-incidence
      models, and Bayesian modelling. The specific data used to create the various risk
      models varies by disease and may include molecular, epidemiologic, and clinical
      information although, in general, family history remains the primary variable of
      interest, particularly for those diseases for which a susceptibility allele(s)
      has yet to be identified. When permitted by sample size, researchers also attempt
      to measure the effect of any gene-environment interaction. In this paper we give
      an overview of the various definitions of risk as well as several of the more
      frequently used methods of risk estimation in genetic epidemiology at present. In
      addition, the means by which different methods are able to provide a measure of
      error or uncertainty associated with a given risk estimate will be discussed.
      Applications to risk modelling for breast cancer are given the disease for which
      risk assessment has probably been most extensively defined.

PMID- 11308073
TI  - Roles of an endogenous serum lectin in the immune protection of blue gourami,
      Trichogaster trichopterus (Pallus) against Aeromonas hydrophila.
AB  - The serum of blue gourami, Trichogaster trichopterus (Pallus), contains a calcium
      dependent, N-acetyl-galactosamine-binding lectin (BGL) which efficiently
      activates and enhances the non-specific immune response of fish towards a
      virulent strain of Aeromonas hydrophila. In the in vitro studies, a lectin
      concentration range of 0.05-1.0 ng ml(-1) was found to significantly promote
      phagocytic uptake of the bacteria by macrophages. This effect was further
      augmented when purified lectin was combined with laminarin (beta-1,3-D-glucan).
      Supernatants obtained from these lectin-stimulated macrophage cultures also
      exhibited significant bacteria-killing activities. In addition, complement from
      naive fish serum, in the presence of purified BGL, was able to kill A.
      hydrophila. Finally, challenge experiments demonstrated that BGL could confer
      effective immune protection to naive blue gourami against an Aeromonas infection.

PMID- 11308074
TI  - Mucosal immune response of spotted sand bass Paralabrax maculatofasciatus
      (Steindachner, 1868) orally immunised with an extracellular lectin of Aeromonas
      veronii.
AB  - To assess the immunogenic and immunoprotective role of the extracellular lectin
      from Aeromonas veronii (MCBP), which has affinity for mucosal constituents such
      as mucin, lactoferrin, immunoglobulins and collagen, spotted sand bass
      (Paralabrax maculatofasciatus) were orally immunised either with soluble MCBP,
      adjuvant-conjugated MCBP or immobilised MCBP on latex microspheres. The results
      suggest that the MCBP is capable of eliciting protective immunity against A.
      veronii infections when administered orally. The highest mucosal immune response
      was elicited in fish immunised with MCBP covalently linked to cholera toxin B
      subunit (CTB) or to Escherichia coli heat-labile toxin (hLT). MCBP-CTB was found
      to elicit immunoprotection against a challenge with live Aeromonas cells with a
      relative percent survival of almost 70% and without the expression of the severe
      histopathological alterations induced by A. veronii.

PMID- 11308075
TI  - A monoclonal antibody recognising a surface marker on rainbow trout (Oncorhynchus
      mykiss) monocytes.
AB  - The characterisation of a monoclonal antibody (mab 45) reacting with phagocytic
      leucocytes isolated from blood and spleen of rainbow trout (Oncorhynchus mykiss,
      Walbaum) is described. The surface marker labelled by this mab is expressed at
      relative low levels on the membrane of large, nearly nongranulated trout
      leucocytes, and having the typical morphology of monocytes in flow cytometry
      (Kfoury et al., 1999, Fish Pathology, 34, 1-6). No reaction of mab 45 with
      granulocytes, lymphocytes or thrombocytes was detected. In spleen and head
      kidney, large, polymorphonuclear leucocytes were immunostained. The mab most
      strongly recognised an antigen of 48 kDa prepared from trout leucocytes of
      different organs, but not in trout plasma. In an in vitro phagocytosis assay
      trout monocytes were stained with mab 45 after phagocytosis of Aeromonas
      salmonicida labelled with the lipophilic fluorescent cell surface linker PKH26.
      However, previous binding of mab 45 on trout leucocytes did not inhibit the
      phagocytosis of A. salmonicida particles. Using mab 45, the dynamics of monocytes
      in blood, spleen and peritoneal cavity could be demonstrated after
      intraperitoneal injection of trout with inactivated A. salmonicida. The described
      mab serves as a useful tool to investigate the involvement of
      monocytes/macrophages in immune reactions of trout to a variety of pathogens.

PMID- 11308076
TI  - Response of haemocyte lysosomes to bacterial inoculation in the oysters Ostrea
      edulis L. and Crassostrea gigas (Thunberg) and the scallop Pecten maximus (L).
AB  - Data are presented that demonstrate the application of the neutral red retention
      assay (NRR) to monitor the effects of a bacterial inoculation on the haemocyte
      lysosomes of the European flat oyster Ostrea edulis, Pacific oyster Crassostrea
      gigas and scallop Pecten maximus. Bivalves were acclimated to three temperature
      regimes (5, 15 and 25 degrees C), at constant salinity for 7 days in the
      laboratory. Once baseline responses to acclimation temperature had been
      established, the effects of an in vivo inoculation on haemocyte lysosomal
      stability were assessed using the NRR assay. Lysosomal membrane stability was
      reduced in the presence of bacteria for all three species of bivalve, but
      destabilisation of C. gigas haemocyte lysosomes appeared to be most sensitive to
      the presence of the bacterium Listonella anguillarum. For all three bivalve
      species, the reduction in lysosomal stability appeared to be proportional to the
      growth of the bacterial inoculate. Using appropriate controls, the NRR assay was
      demonstrated to have great potential as a tool with which to make rapid initial
      assessments of the immune status of bivalve molluscs.

PMID- 11308077
TI  - Rainbow trout offspring with different resistance to viral haemorrhagic
      septicaemia.
AB  - To study immunological and immunogenetical parameters related to resistance
      against viral haemorrhagic septicaemia (VHS), attempts to make gynogenetic
      strains of rainbow trout selected for high and low resistance to VHS were
      initiated in 1988. The first gynogenetic generation of inbreeding resulted in the
      more resistant offspring E8 and the low resistance offspring K3; the K3 offspring
      having the same high mortality as the susceptible reference strain of outbred
      trout in infection trials. A second gynogenetic generation derived from the E8
      strain resulted in some low resistance offspring, and two gynogenetic families in
      which all, or nearly all, fish survived challenge with VHS virus. In this study,
      an attempt to associate the distribution of different MHC class II genotypes with
      low and high resistance gynogenetic offspring was performed. Two different MHC
      haplotypes could be distinguished, and in both low and high resistance families
      all three genotypes were found, which could be explained by the fact that the
      mother fish carried the heterozygous genotype. Although no significant
      differences in MHC II genotypes were found between the high and low resistance
      offspring, a significantly different distribution of haplotypes in the low
      resistance offspring was observed, that could not be explained by a one- or two
      locus model.

PMID- 11308078
TI  - Characterisation of growth enhancing factor production in different phases of in
      vitro fish macrophage development.
AB  - We previously described the release of macrophage growth factor(s) (MGF) into
      culture supernatants (CCM) by a goldfish macrophage cell line (GMCL) and in vitro
      derived kidney macrophages (IVDKM). In this study, we report that IVDKM growth
      can be subdivided into three developmental phases, defined using both
      morphological and flow cytometric characteristics: a lag phase, a proliferative
      phase, and a senescence phase. Analysis of the growth inducing capabilities of
      CCM indicated that maximum activity was consistently found in supernatants
      isolated from IVDKM cultures during the proliferative phase of development. In
      contrast, CCM from the senescence phase proved to be poor inducers of macrophage
      growth. Overall, we identify a link between the seeding-CCM composition, the
      extent of IVDKM growth and the rate of entrance into a senescent state
      characterised by IVDKM apoptotic cell death. Use of IVDKM CCM obtained at the
      peak of macrophage growth maximised macrophage growth factor (MGF) activity, and
      prevented the introduction of negative regulators of IVDKM proliferation, which
      will contribute significantly to our MGF purification efforts. Furthermore, the
      collection of IVDKM, prior to their commitment into apoptotic pathways, will
      prove to be essential in the selection of specific cell subsets for studies of
      antimicrobial mechanisms of macrophages.

PMID- 11308079
TI  - Effects of short-term crowding stress on the gilthead seabream (Sparus aurata L)
      innate immune response.
AB  - Gilthead seabream specimens were subjected to an intense short-term crowding
      stress of 100 kg m(-3) for 2 h. After 0, 1, 2, 3 and 4 days, blood glucose and
      serum cortisol levels, serum complement activity, phagocytic and respiratory
      burst activities of head-kidney leucocytes, and the percentage of monocyte/
      macrophages and granulocytes in head-kidney and circulating blood were
      determined. An immediate effect of the stress was a depression in complement and
      phagocytic activities, both of which recovered after 3 or 2 days, respectively,
      while respiratory burst remained unaffected. The depression of phagocytosis in
      head-kidney leucocytes seemed to correlate with stress-induced migration of
      active cells from the organ to circulating blood. The present results point to
      the importance of minimising intense short-term crowding stress in order to
      reduce possible states of immunodepression in farmed fish.

PMID- 11308080
TI  - Luciferase expression 2 years after DNA injection in glass catfish (Kryptopterus
      bicirrhus).
AB  - Glass catfish (Kryptopterus bicirrhus) have transparent muscles and skin.
      Intramuscular injection of DNA encoding luciferase into these fish induced
      luciferase expression that was measurable in vivo with a low light video image
      analyser. Expression could be detected up to at least 2 years after DNA
      injection. Although luciferase is not representative of all types of antigen,
      this study stresses the need for future studies directed to limit the period of
      antigen expression after DNA vaccination.

PMID- 11308081
TI  - Perspective: the origin of flowering plants and their reproductive biology--a
      tale of two phylogenies.
AB  - Recently, two areas of plant phylogeny have developed in ways that could not have
      been anticipated, even a few years ago. Among extant seed plants, new
      phylogenetic hypotheses suggest that Gnetales, a group of nonflowering seed
      plants widely hypothesized to be the closest extant relatives of angiosperms, may
      be less closely related to angiosperms than was believed. In addition, recent
      phylogenetic analyses of angiosperms have, for the first time, clearly identified
      the earliest lineages of flowering plants: Amborella, Nymphaeales, and a clade
      that includes Illiciales/ Trimeniaceae/Austrobaileyaceae. Together, the new seed
      plant and angiosperm phylogenetic hypotheses have major implications for
      interpretation of homology and character evolution associated with the origin and
      early history of flowering plants. As an example of the complex and often
      unpredictable interplay of phylogenetic and comparative biology, we analyze the
      evolution of double fertilization, a process that forms a diploid embryo and a
      triploid endosperm, the embryo-nourishing tissue unique to flowering plants. We
      demonstrate how the new phylogenetic hypotheses for seed plants and angiosperms
      can significantly alter previous interpretations of evolutionary homology and
      firmly entrenched assumptions about what is synapomorphic of flowering plants. In
      the case of endosperm, a solution to the century-old question of its potential
      homology with an embryo or a female gametophyte (the haploid egg-producing
      generation within the life cycle of a seed plant) remains complex and elusive.
      Too little is known of the comparative reproductive biology of extant
      nonflowering seed plants (Gnetales, conifers, cycads, and Ginkgo) to analyze
      definitively the potential homology of endosperm with antecedent structures.
      Remarkably, the new angiosperm phylogenies reveal that a second fertilization
      event to yield a biparental endosperm, long assumed to be an important
      synapomorphy of flowering plants, cannot be conclusively resolved as ancestral
      for flowering plants. Although substantive progress has been made in the analysis
      of phylogenetic relationships of seed plants and angiosperms, these efforts have
      not been matched by comparable levels of activity in comparative biology. The
      consequence of inadequate comparative biological information in an age of
      phylogenetic biology is a severe limitation on the potential to reconstruct key
      evolutionary historical events.

PMID- 11308082
TI  - Developmental interactions and the constituents of quantitative variation.
AB  - Development is the process by which genotypes are transformed into phenotypes.
      Consequently, development determines the relationship between allelic and
      phenotypic variation in a population and, therefore, the patterns of quantitative
      genetic variation and covariation of traits. Understanding the developmental
      basis of quantitative traits may lead to insights into the origin and evolution
      of quantitative genetic variation, the evolutionary fate of populations, and,
      more generally, the relationship between development and evolution. Herein, we
      assume a hierarchical, modular structure of trait development and consider how
      epigenetic interactions among modules during ontogeny affect patterns of
      phenotypic and genetic variation. We explore two developmental models, one in
      which the epigenetic interactions between modules result in additive effects on
      character expression and a second model in which these epigenetic interactions
      produce nonadditive effects. Using a phenotype landscape approach, we show how
      changes in the developmental processes underlying phenotypic expression can alter
      the magnitude and pattern of quantitative genetic variation. Additive epigenetic
      effects influence genetic variances and covariances, but allow trait means to
      evolve independently of the genetic variances and covariances, so that phenotypic
      evolution can proceed without changing the genetic covariance structure that
      determines future evolutionary response. Nonadditive epigenetic effects, however,
      can lead to evolution of genetic variances and covariances as the mean phenotype
      evolves. Our model suggests that an understanding of multivariate evolution can
      be considerably enriched by knowledge of the mechanistic basis of character
      development.

PMID- 11308083
TI  - Divergent evolution of dispersal in a heterogeneous landscape.
AB  - The evolution of dispersal is investigated in a landscape of many patches with
      fluctuating carrying capacities and spatial heterogeneity in temporal
      fluctuations. Although asynchronous temporal fluctuations select for dispersal,
      spatial heterogeneity in the distribution of fluctuating environmental variables
      selects against it. We find evolutionary branching in dispersal rate leading to
      the evolutionarily stable coexistence of a high- and a low-dispersal phenotype.
      We study how the opposing forces of selection for and against dispersal change
      with the relative size and the environmental qualities of the source and sink
      habitats. Our results suggest that the evolution of dispersal dimorphism could be
      a first step towards speciation and local adaptation.

PMID- 11308084
TI  - Two-generation analysis of pollen flow across a landscape. I. Male gamete
      heterogeneity among females.
AB  - Gene flow is a key factor in the spatial genetic structure in spatially
      distributed species. Evolutionary biologists interested in microevolutionary
      processess and conservation biologists interested in the impact of landscape
      change require a method that measures the real time process of gene movement. We
      present a novel two-generation (parent-offspring) approach to the study of
      genetic structure (TwoGener) that allows us to quantify heterogeneity among the
      male gamete pools sampled by maternal trees scattered across the landscape and to
      estimate mean pollination distance and effective neighborhood size. First, we
      describe the model's elements: genetic distance matrices to estimate intergametic
      distances, molecular analysis of variance to determine whether pollen profiles
      differ among mothers, and optimal sampling considerations. Second, we evaluate
      the model's effectiveness by simulating spatially distributed populations.
      Spatial heterogeneity in male gametes can be estimated by phiFT, a male gametic
      analogue of Wright's F(ST) and an inverse function of mean pollination distance.
      We illustrate TwoGener in cases where the male gamete can be categorically or
      ambiguously determined. This approach does not require the high level of genetic
      resolution needed by parentage analysis, but the ambiguous case is vulnerable to
      bias in the absence of adequate genetic resolution. Finally, we apply TwoGener to
      an empirical study of Quercus alba in Missouri Ozark forests. We find that phiFT
      = 0.06, translating into about eight effective pollen donors per female and an
      effective pollination neighborhood as a circle of radius about 17 m. Effective
      pollen movement in Q. alba is more restricted than previously realized, even
      though pollen is capable of moving large distances. This case study illustrates
      that, with a modest investment in field survey and laboratory analysis, the
      TwoGener approach permits inferences about landscape-level gene movements.

PMID- 11308085
TI  - Using genetic markers to directly estimate male selection gradients.
AB  - We present an analysis of Raphanus raphanistrum and simulations illustrating the
      utility of directly estimating male phenotypic selection gradients using genetic
      markers. The method offers a much more refined characterization of selection than
      attempting to assign paternity to individual progeny. Our analysis of R.
      raphanistrum reveals selection on remarkably fine features of floral morphology,
      including anther exsertion, that were opaque to previous approaches. The new
      results also undermine a previous conclusion that selection on wild radish floral
      morphology acts primarily through female fitness. Simulation results show that
      selection gradients on the order of beta = 0.1-0.2 can be readily detected with
      allozyme markers in moderate-sized (< 200 paternal individuals) populations.
      Highly polymorphic (e.g., microsatellite) markers will likely detect fine scale
      selection (beta < 0.1) in larger populations (> or = 400 individuals). Increased
      progeny sample size, by sampling either additional maternal families or more
      progeny per maternal parent, partly compensates for low exclusion probability.
      Increasing the number of possible fathers without changing progeny sample size
      decreases the ability to detect selection, especially at lower exclusion
      probabilities. Sampling only some male genotypes reduces the power to detect
      selection and biases (underestimates) the magnitude of the selection gradient
      estimate.

PMID- 11308086
TI  - The influence of a competitor on the geographic mosaic of coevolution between
      crossbills and lodgepole pine.
AB  - The geographic mosaic theory of coevolution posits that the form of selection
      between interacting species varies across a landscape with coevolution important
      and active in some locations (i.e., coevolutionary hotspots) but not in others
      (i.e., coevolutionary coldspots). We tested the hypothesis that the presence of
      red squirrels (Tamiasciurus hudsonicus) affects the occurrence of coevolution
      between red crossbills (Loxia curvirostra complex) and Rocky Mountain lodgepole
      pine (Pinus contorta ssp. latifolia) and thereby provides a mechanism giving rise
      to a geographic mosaic of selection. Red squirrels are the predominant
      predispersal seed predator and selective agent on lodgepole pine cones. However,
      in four isolated mountain ranges east and west of the Rocky Mountains, red
      squirrels are absent and red crossbills are the main predispersal seed predator.
      These isolated populations of pine have apparently evolved without Tamiasciurus
      for about 10,000 to 12,000 years. Based on published morphological, genetic, and
      paleobotanical studies, we infer that cone traits in these isolated populations
      that show parallel differences from cones in the Rocky Mountains have changed in
      parallel. We used data on crossbill and conifer cone morphology and feeding
      preferences and efficiency to detect whether red crossbills and lodgepole pine
      exhibit reciprocal adaptations, which would imply coevolution. Cone traits that
      act to deter Tamiasciurus and result in high ratios of cone mass to seed mass
      were less developed in the isolated populations. Cone traits that act to deter
      crossbills include larger and thicker scales and perhaps increased overlap
      between successive scales and were enhanced in the isolated populations. In the
      larger, isolated mountain ranges crossbills have evolved deeper, shorter, and
      therefore more decurved bills to exploit these cones. This provides crossbills
      with higher feeding rates, and the change in bill shape has improved efficiency
      by reducing the concomitant increases in body mass and daily energy expenditures
      that would have resulted if only bill size had increased. These parallel
      adaptations and counter adaptations in red crossbills and lodgepole pine are
      interpreted as reciprocal adaptations and imply that these crossbills and pine
      are in coevolutionary arms races where red squirrels are absent (i.e.,
      coevolutionary hotspots) but not where red squirrels are present (i.e.,
      coevolutionary cold-spots).

PMID- 11308087
TI  - A comparative study of asymmetric migration events across a marine biogeographic
      boundary.
AB  - In many nonclonal, benthic marine species, geographic distribution is mediated by
      the dispersal of their larvae. The dispersal and recruitment of marine larvae may
      be limited by temperature gradients that can affect mortality or by ocean
      currents that can directly affect the movements of pelagic larvae. We focus on
      Point Conception, a well-known biogeographic boundary between the Californian and
      Oregonian biogeographic provinces, to investigate whether ocean currents affect
      patterns of gene flow in intertidal marine invertebrates. The predominance of
      pelagically dispersing species with northern range limits at Point Conception
      suggests that ocean currents can affect species distributions by erecting
      barriers to the dispersal of planktonic larvae. In this paper, we investigate
      whether the predominantly southward currents have left a recognizable genetic
      signature in species with pelagically dispersing larvae whose ranges span Point
      Conception. We use patterns of genetic diversity and a new method for inferring
      cladistic migration events to test the hypothesis that southward currents
      increase southward gene flow for species with pelagically dispersing larvae. We
      collected mitochondrial DNA (mtDNA) sequence data for the barnacles Balanus
      glandula and Chthamalus fissus and also reanalyzed a previously published mtDNA
      dataset (Strongylocentrotus purpuratus, Edmands et al. 1996). For all three
      species, our cladistic approach identified an excess of southward migration
      events across Point Conception. In data from a fourth species with nondispersing
      larvae (Nucella emarginata, Marko 1998), our method suggests that ocean currents
      have not played a role in generating genetic structure.

PMID- 11308088
TI  - Colony structure of a slavemaking ant. I. Intracolony relatedness, worker
      reproduction, and polydomy.
AB  - Colony and population structure of the obligate slavemaker ant Protomognathus
      americanus was analyzed via four nuclear microsatellite loci and mitochondrial
      DNA (mtDNA) markers. Colonies of P. americanus usually contain a single queen,
      and here we show that she is singly inseminated. Nestmate workers are generally
      full sisters and their relatedness does not deviate from the expected value of
      0.75. Even though colonies were strictly monogynous, we were able to infer that
      colony takeover by related queens was common and queen replacement by unrelated
      queens was rare. Polydomy is widespread, with neighboring nests having the same
      genetic composition. Although we found no evidence of population viscosity or
      inbreeding from nuclear markers, mtDNA markers provided evidence for small-scale
      genetic structuring. Haplotype structuring and takeover by related queens suggest
      philopatry of newly mated queens. In this species, workers reproduce in
      queenright and queenless nests and worker reproduction accounts for more than 70%
      of all males. Although sex-ratio theory points to slavemaking ants as important
      systems for studying queen-worker conflict, our results indicate no basis for
      such conflict in P. americanus, because extensive worker reproduction generates
      shifts in relatedness values. Rather, the dual effects of independent polydomous
      nest units and local resource competition among queens produce male-biased
      allocation ratios in this species.

PMID- 11308089
TI  - Colony structure of a slavemaking ant. II. Frequency of slave raids and impact on
      the host population.
AB  - The parasite pressure exerted by the slavemaker ant Protomognathus americanus on
      its host species Leptothorax longispinosus was analyzed demographically and
      genetically. The origin of slaves found in colonies of the obligate slavemaker
      was examined with nuclear and mitochondrial DNA markers to make inferences about
      the frequency and severity of slave raids. Relatedness of enslaved L.
      longispinosus workers in the same nest was very low, and our data suggest that,
      on average, each slavemaker nest raids six host colonies per season. Therefore,
      the influence of slavemaker species on their hosts is much stronger than simple
      numerical ratios suggest. We also found that slave relatedness was higher in
      small than in large slavemaker nests; thus, larger nests wield a much stronger
      influence on the host. We estimated that in the study population, on average, a
      host nest has a 50% chance of being attacked by a slavemaker colony per year.
      Free-living Leptothorax colonies in the vicinity of slavemaker nests did not
      represent the source of slaves working in P. americanus colonies, which suggests
      that raided nests either do not survive or migrate after being raided. Colony
      composition and intranest relatedness of free-living L. longispinosus colonies
      differed markedly between areas with slavemakers and those that are parasite
      free. In the presence of slavemakers, host colonies were less likely to be
      polygynous and had fewer workers and a higher relatedness among worker brood.
      Host nests with slavemaker neighbors allocated more resources into sexuals,
      possibly caused by these shifts in nest demography. Finally, enslaved Leptothorax
      workers in P. americanus nests appeared to be less efficient than their
      counterparts in free-living colonies. Thus, slavemakers exert a much stronger
      impact on their hosts than had previously been suspected and represent an unique
      system to study parasite-host coevolution.

PMID- 11308090
TI  - Male size, sperm transfer, and colony fitness in the western harvester ant,
      Pogonomyrmex occidentalis.
AB  - Mating success in the western harvester ant, Pogonomyrmex occidentalis, increases
      with male size. We tested the hypothesis that increased mating success increases
      male fitness and the fitness of colonies that make large males by comparing the
      sperm content of males prior to and at the conclusion of the mating swarm. The
      number of sperm a male initially possesses is a function of male size, and large
      males transfer a greater proportion of their sperm than do small males. For
      colonies, the payoff per unit of investment is an increasing function of male
      size, and investment in large males is not equivalent to investing in a larger
      number of small males. Allocation ratios in species that show size variation in
      reproductives may need to be modified by the individual fitness functions.

PMID- 11308091
TI  - Heterochrony, maternal effects, and phenotypic variation among sympatric
      pupfishes.
AB  - Variation in ontogeny can produce phenotypic variation both within and among
      species. I investigated whether changes in timing and rate of growth were a
      source of phenotypic variation in a putative incipient species group of pupfish
      (Cyprinodon spp.). On San Salvador Island, Bahamas, sympatric forms of pupfish
      differ in morphology but show only partial reproductive isolation in the
      laboratory. Offspring from two forms and two geographical areas and their hybrids
      were bred in the laboratory, and ontogenetic trajectories of their feeding
      morphology were followed until maturity. In the Bahamian pupfish the two forms
      grow along similar size but not shape trajectories. Two heterochronic parameters,
      onset and rate of growth, alter shape trajectories in the Bahamian pupfish.
      Similar forms from different geographical areas (Florida and the Bahamas) grow
      along parallel shape trajectories, differing only in one heterochronic parameter,
      the onset shape. Hybrids within and between the pupfish forms produced
      intermediate feeding morphologies that were influenced by their maternal
      phenotype, suggesting that maternal effects may be a source of phenotypic
      variation in shape that can persist to maturity. In Cyprinodon, small changes in
      multiple heterochronic parameters translate into large phenotypic differences in
      feeding morphology.

PMID- 11308092
TI  - Phylogeography of the plains killifish, Fundulus zebrinus.
AB  - Drainage systems of the Great Plains and western Gulf Slope underwent substantial
      changes through diversions and stream captures during the Pleistocene, either as
      the result of the glacial advances or through independent geologic processes. The
      distributions of a variety of fishes that range across west-central North
      America, such as the plains killifish (Fundulus zebrinus), are thought to be the
      product of this Pleistocene influence. We examined the geographic pattern of
      genetic variation in F. zebrinus using three allozyme loci (n = 793),
      mitochondrial DNA restriction fragment length polymorphisms (RFLPs, n = 352), and
      sequencing of the mitochondrial cytochrome oxidase I (COI, n = 23) in an attempt
      to understand the roles of dispersal and vicariance. The phylogeographic patterns
      were concordant between the allozyme and mitochondrial data with the exception of
      the population in the North Canadian River. The populations fell into three
      geographic assemblages, which we designated as northern, central, and southern. A
      large phylogenetic break (average Roger's D = 0.702; average sequence divergence
      in RFLPs = 4.6%; average sequence divergence in COI = 5.5%) separated the
      northern/central and southern assemblages. The northern region was likely
      colonized sometime during the mid-Pleistocene. Fish in the Brazos and Pecos
      Rivers probably reached these drainages through stream captures of the Red River.
      The large phylogenetic break between the northern/central and southern clades
      supports previous attempts to recognize two species of plains killifish: F.
      zebrinus and F. kansae.

PMID- 11308093
TI  - The evolutionary history of brown trout (Salmo trutta L.) inferred from
      phylogeographic, nested clade, and mismatch analyses of mitochondrial DNA
      variation.
AB  - Phylogeographic, nested clade, and mismatch analyses of mitochondrial DNA (mtDNA)
      variation were used to infer the temporal dynamics of distributional and
      demographic history of brown trout (Salmo trutta). Both new and previously
      published data were analyzed for 1,794 trout from 174 populations. This combined
      analysis improved our knowledge of the complex evolutionary history of brown
      trout throughout its native Eurasian and North African range of distribution in
      many ways. It confirmed the existence of five major evolutionary lineages that
      evolved in geographic isolation during the Pleistocene and have remained largely
      allopatric since then. These should be recognized as the basic evolutionarily
      significant units within brown trout. Finer phylogeographic structuring was also
      resolved within major lineages. Contrasting temporal juxtaposition of different
      evolutionary factors and timing of major demographic expansions were observed
      among lineages. These unique evolutionary histories have been shaped both by the
      differential latitudinal impact of glaciations on habitat loss and potential for
      dispersal, as well as climatic impacts and landscape heterogeneity that
      translated in a longitudinal pattern of genetic diversity and population
      structuring at more southern latitudes. This study also provided evidence for the
      role of biological factors in addition to that of physical isolation in limiting
      introgressive hybridization among major trout lineages.

PMID- 11308094
TI  - Countergradient variation and secondary sexual color: phenotypic convergence
      promotes genetic divergence in carotenoid use between sympatric anadromous and
      nonanadromous morphs of sockeye salmon (Oncorhynchus nerka).
AB  - Genetically distinct anadromous (sockeye) and nonanadromous (kokanee) morphs of
      the Pacific salmon, Oncorhynchus nerka, develop identical, brilliant red color at
      maturity during sympatric breeding in freshwater streams. The marine and
      lacustrine environments they occupy prior to maturity, however, appear to differ
      in the availability of dietary carotenoid pigments necessary to produce red
      coloration. We tested the hypothesis that kokanee, which occupy carotenoid-poor
      lakes, are more efficient at using the dietary pigments than are sockeye, which
      occupy the more productive North Pacific Ocean. In a 2-year controlled breeding
      study, flesh and skin color of mature and immature crosses fed a low-carotenoid
      diet were quantified with both a chromameter and by chemical extraction of
      carotenoid pigments. Results revealed striking countergradient variation in
      carotenoid use, with kokanee approximately three times more efficient at
      sequestering the pigments to the flesh musculature than similar age sockeye. This
      difference translated into virtually nonoverlapping differences between pure
      crosses in secondary sexual color at maturity, when the pigments are mobilized
      and transported to the skin. Kokanee crosses turned pinkish red over most of
      their body, whereas sockeye turned olive green. The olive green was similar to
      the breeding color of residuals in the wild, the progeny of anadromous sockeye
      that remain in fresh water and are believed to have given rise to kokanee on
      numerous independent occasions. Reciprocal hybrids were similar to each other and
      intermediate to the pure crosses, indicating additive genetic inheritance. Mate
      choice trials with sockeye males in the wild showed the ancestral morph strongly
      preferred red over green models. These results suggest a preference for red mates
      maintained in nonanadromous breeding populations drove the reevolution of the red
      phenotype in kokanee via more efficient use of dietary carotenoid pigments. This
      is a novel, yet hidden, mechanism by which sexual selection promotes the genetic
      differentiation of these sympatric populations.

PMID- 11308095
TI  - The contribution of phenotypic plasticity to adaptation in Lacerta vivipara.
AB  - Correlation between intraspecific phenotypic variability and variation of
      environmental conditions could reflect adaptation. Different phenotypes may
      result from differential expression of a genotype in different environments
      (phenotypic plasticity) or from expression of different genotypes (genetic
      diversity). Populations of Lacerta vivipara exhibit larger adult body length,
      lower age at maturity, higher fecundity, and smaller neonatal size in humid
      habitats compared to dry habitats. We conducted reciprocal transplants of
      juvenile L. vivipara to test for the genetic or plastic origin of this variation.
      We captured gravid females from four populations that differed in the relative
      humidity of their habitats, and during the last 2 to 4 weeks of gestation, we
      manipulated heat and water availability under laboratory conditions. Juveniles
      were released into the different populations and families were divided to compare
      growth rate and survival of half-sibs in two environments. Growth rate and
      survival were assessed using capture-recapture techniques. Growth rate was
      plastic in response to postnatal conditions and did not differ between
      populations of origin. Survival differed between populations of origin, partially
      because of differences in neonatal body length. The response of juvenile body
      length and body condition to selection in the different habitats was affected by
      the population of origin. This result cannot be simply interpreted in terms of
      adaptation; however, phenotypic plasticity of fecundity or juvenile size most
      probably resulted in adaptive reproductive strategies. Adaptation to the habitat
      by means of genetic specialization was not detected. Further investigation is
      needed to discriminate between genetic and long-term maternal effects.

PMID- 11308096
TI  - Plumage and mitochondrial DNA haplotype variation across a moving hybrid zone.
AB  - We analyze variation in phenotypes and mitochondrial DNA (mtDNA) haplotypes over
      the breeding ranges of hermit and Townsend's warblers and across two of their
      three hybrid zones. Within these two hybrid zones, we demonstrate that the
      placement, shape, and width of transitions in seven plumage characters are
      remarkably similar, suggesting that a balance between dispersal and sexual
      selection keeps these hybrid zones narrow. A consistent asymmetry in these
      character transition curves suggests that Townsend's warblers have a selective
      advantage over hermit warblers, which is presumably due to the aggressive
      superiority of Townsend's over hermit males (Pearson and Rohwer 2000). An
      association between plumage and mtDNA haplotypes shows that pure Townsend's
      warblers, but not pure hermit warblers, immigrate into these hybrid zones,
      further supporting the competitive superiority of Townsend's warblers over hermit
      warblers. The mitochondrial haplotype transitions across these hybrid zones are
      much wider than the phenotypic transitions and provide no indication that the
      mtDNA haplotypes representing these two warblers are selectively maintained. More
      importantly, the phenotypically pure populations of Townsend's warblers
      throughout a 2,000-km coastal strip north of the Washington hybrid zones contain
      a preponderance of hermit warbler mtDNA haplotypes. This result suggests massive
      movement of the hybrid zone between these warblers during the 5,000 years since
      their most recent interglacial contact. We develop a model to explain the
      phenotypic and genetic divergence between these warblers and the evolution of
      their dramatic differences in aggressiveness; we also show how differences in
      male aggression, in combination with biased pairing patterns, can explain the
      haplotype footprint recording the historical movement of this hybrid zone.

PMID- 11308097
TI  - Natural selection and quantitative genetics of life-history traits in Western
      women: a twin study.
AB  - Whether contemporary human populations are still evolving as a result of natural
      selection has been hotly debated. For natural selection to cause evolutionary
      change in a trait, variation in the trait must be correlated with fitness and be
      genetically heritable and there must be no genetic constraints to evolution.
      These conditions have rarely been tested in human populations. In this study,
      data from a large twin cohort were used to assess whether selection will cause a
      change among women in a contemporary Western population for three life-history
      traits: age at menarche, age at first reproduction, and age at menopause. We
      control for temporal variation in fecundity (the "baby boom" phenomenon) and
      differences between women in educational background and religious affiliation.
      University-educated women have 35% lower fitness than those with less than seven
      years education, and Roman Catholic women have about 20% higher fitness than
      those of other religions. Although these differences were significant, education
      and religion only accounted for 2% and 1% of variance in fitness, respectively.
      Using structural equation modeling, we reveal significant genetic influences for
      all three life-history traits, with heritability estimates of 0.50, 0.23, and
      0.45, respectively. However, strong genetic covariation with reproductive fitness
      could only be demonstrated for age at first reproduction, with much weaker
      covariation for age at menopause and no significant covariation for age at
      menarche. Selection may, therefore, lead to the evolution of earlier age at first
      reproduction in this population. We also estimate substantial heritable variation
      in fitness itself, with approximately 39% of the variance attributable to
      additive genetic effects, the remainder consisting of unique environmental
      effects and small effects from education and religion. We discuss mechanisms that
      could be maintaining such a high heritability for fitness. Most likely is that
      selection is now acting on different traits from which it did in pre-industrial
      human populations.

PMID- 11308098
TI  - Rapid loss of stress resistance in Drosophila melanogaster under adaptation to
      laboratory culture.
AB  - We investigate changes in resistance to desiccation and starvation during
      adaptation of Drosophila melanogaster to laboratory culture. We test the
      hypothesis that resistance to environmental stresses is lost under laboratory
      adaptation. For both traits, there was a rapid loss of resistance over a three
      year period. The rapidity of the response suggested that mutation accumulation
      could not account for it. Rather, resistance to environmental stresses appeared
      to be lost as a correlated response to selection on another trait, such as early
      fertility, with which stress resistance is negatively genetically correlated.
      These results suggest that caution is needed when extrapolating from evolution of
      stress resistance in long-established laboratory stocks to patterns of responses
      and correlated responses in natural populations.

PMID- 11308099
TI  - Geographic variation and the evolution of reproductive allocation in the pitcher
      plant mosquito, Wyeomyia smithii.
AB  - We measured the egg size of six geographic populations of the pitcher-plant
      mosquito, Wyeomyia smithii, from Florida (30 degrees N) to Ontario (49 degrees
      N). Populations from northern latitudes produced larger eggs than populations
      from southern latitudes. Egg size increased with increasing latitude more rapidly
      when larvae were reared under low rather than high density. One southern (30
      degrees N) and one northern (49 degrees N) population of W. smithii that
      persisted through 10 generations of selection for increased persistence under
      conditions of chronic thermal- and nutrient-limiting stress (conditions similar
      to southern rather than northern habitats) produced smaller eggs more rapidly
      than unselected control lines. However, there were no differences in lifetime
      fecundity or fertility between control and selected lines. Thus, laboratory
      evolution in an environment representative of extreme southern latitudes caused
      evolutionary changes consistent with geographic patterns of egg size. These
      results implicate temperature as a selective factor influencing the geographic
      variation of egg size in W. smithii, and demonstrate a novel trade-off in
      reproductive allocation between egg size and egg maturation time.

PMID- 11308100
TI  - Sexy streamers? The role of natural and sexual selection in the evolution of
      hirundine tail streamers.

PMID- 11308101
TI  - Hypothetical mechanisms of the initial evolution of sexually dimorphic tail
      streamers in Hirundinidae.

PMID- 11308102
TI  - Some of my best friends are physicians.

PMID- 11308103
TI  - Caring for pregnant teenagers: medicolegal issues for nurses.
AB  - From statutory rape, pregnancy options, mandatory reporting, and emancipation, a
      wide range of medicolegal issues face teenagers. These issues become even more
      complex when the teenager is pregnant. Nurses caring for pregnant and parenting
      teenagers are in a position to offer advocacy and support in family planning,
      prenatal, obstetric, and pediatrics settings. A comprehensive understanding of
      common medicolegal issues facing teenagers will help to ensure appropriate
      patient advocacy.

PMID- 11308104
TI  - HIV prevention in single, urban women: condom-use readiness.
AB  - OBJECTIVE: To understand women's readiness to use condoms and their perceived
      pros and cons for condom use. DESIGN: Comparative, descriptive design guided by
      the Transtheoretical Model. SETTING: Data were collected at two urban primary
      health care centers in western New York. PARTICIPANTS: 364 single urban women
      with steady (main) or other (casual, concurrent, multiple, new) sexual partners.
      Most participants were young (mean age of 27 years), economically disadvantaged
      women of color. MAIN OUTCOME MEASURES: Each participant completed an anonymous
      questionnaire that included items for the stage of change algorithm, decisional
      balance of the pros and cons of condom use, sexual history, and HIV risk
      information. RESULTS: Most women were in the early stages of change (not
      intending to use condoms), but those with other partners were further along in
      the stages of change for condom use than those with steady partners. The pros or
      advantages of condom use differed for these women depending on partner type. The
      change in the balance between the pros and cons occurred as theoretically
      predicted for women with steady and other partners. CONCLUSION: Effectiveness of
      HIV prevention interventions for women may be enhanced if they are tailored to
      both readiness to change and partner type.

PMID- 11308105
TI  - Incubators versus mothers' arms: body temperature conservation in very-low-birth
      weight premature infants.
AB  - OBJECTIVE: To determine whether there is a significant difference between the
      temperatures of very-low-birth-weight (VLBW) premature infants in the incubator
      and in the mothers' arms. DESIGN: Repeated measures, with random assignment to
      treatment order and the infants serving as their own controls. SETTING: A 40-bed
      tertiary-level nursery in a university teaching hospital. PARTICIPANTS: A
      convenience sample of 20 preterm infants weighing 1,095 to 1,500 g and from 30 to
      37 weeks postconceptional age. The infants were screened for factors that would
      interfere with temperature maintenance. MAIN OUTCOME MEASURES: Axillary
      temperatures were measured with an electronic thermometer for equal periods of
      time in incubators and mothers' arms. The mean temperature differences between
      the two study conditions were compared using two-tailed t tests and repeated
      analysis of variance (ANOVA). Weight was monitored and analyzed for evidence of
      increased metabolic activity. RESULTS: No significant variations were found in
      the infants' mean temperatures in the incubator, but the infants were
      significantly warmer while in their mothers' arms. CONCLUSION: VLBW premature
      infants can maintain a stable temperature in their mothers' arms without evidence
      of increased metabolic activity. Nurses can encourage mothers to hold their
      infants without fear of cold stress or weight loss.

PMID- 11308106
TI  - Antepartum bed rest: effect upon the family.
AB  - OBJECTIVE: To identify the effects of antepartum bed rest upon the family.
      DESIGN: Descriptive, retrospective survey. PARTICIPANTS: A national random
      selection of 89 women who had been prescribed antepartum bed rest in the hospital
      or at home and who contacted a high-risk pregnancy support group for information.
      MAIN OUTCOME MEASURE: An open-ended questionnaire. RESULTS: Families experienced
      difficulty assuming maternal responsibilities, anxiety about maternalfetal
      outcomes, and adverse emotional effects on the children. Child care was managed
      by various people across time. Child care problems included negative reactions
      from the children, concern about the quality of the provider, and maternal worry
      about care. Families also experienced financial difficulties, the majority of
      which were not compensated by insurance or work benefits. Almost all, 96.6%,
      families received some type of support during bed rest. Instrumental support was
      the most commonly received; however, emotional support was considered the most
      helpful. The least helpful type of support was that which was unreliable. The
      primary providers of support to the family were parents and family, followed by
      friends. The women reported that health care providers offered minimal support to
      the family. CONCLUSION: Despite support, antepartum bed rest creates difficulties
      that affect the entire family and its finances.

PMID- 11308107
TI  - Short-term grief after an elective abortion.
AB  - OBJECTIVE: To identify the short-term grief response after elective abortion.
      DESIGN: Descriptive, comparative study. SETTING: Instruments were administered in
      a women's health clinic. PARTICIPANTS: Ninety-three women, 45 who had a history
      of elective abortion within the past 1 to 14 months and 48 who had never had an
      abortion. Inclusion criteria included no perinatal losses within the past 5
      years; no documented psychiatric history; and ability to read, write, and
      comprehend English. MAIN OUTCOME MEASURES: Nature and intensity of short-term
      grief. RESULTS: Women with a history of elective abortion experienced grief in
      terms of loss of control, death anxiety, and dependency. Although there were no
      statistically significant differences in the intensity of grief in women who had
      a history of elective abortion and the comparison group, there was an overall
      trend toward higher grief intensities in the abortion group. Presence of living
      children, perceived pressure to have the abortion, and the number of abortions
      appear to affect the intensity of the short-term grief response. CONCLUSION:
      Elective abortion has the potential for eliciting a short-term grief response.
      Research is needed to identify which women are at greatest risk. This grief
      response should be acknowledged and appropriate interventions undertaken.

PMID- 11308108
TI  - HIV screening in pregnancy: what women think.
AB  - OBJECTIVE: To describe the experience of screening for human immunodeficiency
      virus (HIV) in pregnancy from the perspective of pregnant women. DESIGN: A
      descriptive study using a sample of pregnant women who had been offered prenatal
      HIV screening. Women participated in semistructured interviews. Transcripts of
      the interviews were analyzed using a combination of grounded theory and content
      analysis to describe their experience of this screening practice. SETTING: Women
      were recruited from tertiary care hospitals, a family practice unit, and a
      community health center in a western Canadian city. PARTICIPANTS: Thirty-two
      pregnant women who ranged in age from 16 to 40 years. Of those interviewed, 21
      consented to screening and 11 declined. RESULTS: The thirty-two women who shared
      their thoughts and feelings all differed in their recollections and opinions.
      Some were not offended by the idea of mandatory screening, whereas others were
      more vocal in their support of women's choices. Most recognized that women want
      healthy infants but were divided in how that responsibility was acted upon. The
      analysis of the interviews yielded six themes. The women described being offered
      the screening test, how they made the decision whether to be tested or not, and
      how they felt while waiting for the test results. They described how the results
      were communicated to them and how they felt on learning the results of the test.
      Finally, the women clarified their thoughts on the way screening is offered.
      CONCLUSIONS: Nurses must continue to inform women of the many and varied choices
      available to them. Nurses also must be respectful of women's decisions and
      recognize the problems inherent in making any kind of screening mandatory.

PMID- 11308109
TI  - Complicated and uncomplicated pregnancies: women's perception of risk.
AB  - OBJECTIVE: To compare the perception of risk of women with complicated and
      uncomplicated pregnancies and to determine the relationship between biomedical,
      psychosocial, and demographic risk factors and women's personal perceptions of
      pregnancy risk. DESIGN: A descriptive, correlational study. SETTING: Antenatal
      units and outpatient clinics of two tertiary care teaching hospitals in western
      Canada. PATIENTS/PARTICIPANTS: A convenience sample of 105 women having a
      complicated pregnancy requiring hospitalization for more than 48 hours and 103
      women with no known complications and no hospitalization during the pregnancy.
      MAIN OUTCOME MEASURE: Perception of risk during pregnancy. RESULTS: Women with
      complicated pregnancies perceived their overall risk and risk for specific
      pregnancy outcomes as significantly higher than women with uncomplicated
      pregnancies. State anxiety and biomedical risk were positively related to
      perception of risk, but there was no relationship between stress, self-esteem, or
      social support and perception of risk. The strongest predictors of self
      perception of pregnancy risk were the biomedical risk score and state anxiety.
      CONCLUSION: Women with complicated pregnancies perceive their risks as higher
      than women with uncomplicated pregnancies. Both biomedical and psychosocial
      factors play a role in influencing risk perception. Nursing assessment of the
      pregnant woman should include discussion with her of her perception of risk.

PMID- 11308110
TI  - The lived experience of premature ovarian failure.
AB  - OBJECTIVE: To describe the lived experience of women who have been diagnosed with
      idiopathic premature ovarian failure (POF). DESIGN: Phenomenology was used to
      achieve the purpose. Women were asked to share their experiences in living with
      premature ovarian failure during an approximately 1-hour interview. The
      interviews were tape-recorded, transcribed, and analyzed for emergent themes.
      SETTING: Interviews were conducted in the participants' homes and in a conference
      room in a hospital. PARTICIPANTS: The six participants were drawn from a
      multicultural sample of women with idiopathic POF. RESULTS: The women in this
      study expressed anger at their health care providers for their perceived lack of
      quality care they had experienced and at the insurance industry for its lack of
      reimbursement for fertility interventions; they expressed depression and sadness
      at the prospective outcome of the diagnosis, mixed emotions regarding their
      significant others, and sadness and resignation about their menopausal symptoms.
      CONCLUSIONS: Health care providers who create an environment in which women and
      their significant others will feel supported in asking questions, be assured that
      their concerns are taken seriously, and be provided with the physical and
      emotional resources they need can help these women to continue to build and live
      their lives.

PMID- 11308111
TI  - Culturally competent care of women and newborns: knowledge, attitude, and skills.
AB  - In a variety of health care settings throughout the United States and Canada,
      nurses are caring for women and newborns from culturally diverse backgrounds. In
      the technologically complex and bureaucratic world of health care delivery,
      cultural considerations in provision of care often are overlooked and neglected.
      The purpose of this article is to define ways in which culturally competent
      nursing care can be implemented. Nursing education and clinical practice
      guidelines are clear on the importance of gaining cultural competence. Providing
      culturally competent care includes understanding the dimensions of culture;
      moving beyond the biophysical to a more holistic approach; and seeking to
      increase knowledge, change attitudes, and hone clinical skills. Building on the
      strengths of women rather than utilizing a deficit model of health care is an
      essential part of providing culturally competent care. The achievement of both
      measurable and "soft" outcomes related to the delivery of culturally competent
      care can make a critical difference in the heath and well-being of women and
      newborns.

PMID- 11308112
TI  - Breastfeeding care in multicultural populations.
AB  - Although the number and diversity of minority women in the United States is
      growing, breastfeeding rates remain low. Nurses can increase breastfeeding rates
      in minority populations if they are aware of and appreciate cultural differences.
      Following an overview of culture's effect on breastfeeding, this article focuses
      on practical aspects of caring for breastfeeding mothers in various cultural
      groups. Breastfeeding educational programs are effective when they are culturally
      sensitive and emerge from the culture itself.

PMID- 11308113
TI  - Health promotion and risk reduction in Malawi, Africa, village women.
AB  - OBJECTIVE: A train-the-trainer intervention was evaluated in which village
      leaders in Malawi, Africa, taught other villagers how to improve their health.
      DESIGN: Health knowledge and reported health practices were compared before and
      after the educational intervention in 15 villages in Chimutu, Malawi, Africa.
      SETTING: Surveys were completed by trained data gatherers in the village setting.
      PATIENTS/PARTICIPANTS: All men and women of childbearing age who were present in
      the village when data collection occurred were asked to participate. There were
      187 participants in the preintervention survey and 175 participants in the
      postintervention survey. INTERVENTION: Seventy-six village women were trained,
      using low literacy techniques, to provide content on health promotion and risk
      reduction in pregnancy. Over 20,000 persons have received at least one health
      teaching session from the village trainers. RESULTS: The intervention resulted in
      reported changes in prenatal and postpartum care and in more births occurring in
      the hospital or clinic. Some positive nutritional changes were reported, although
      few changes in beliefs about use of herbal medicines or about the use of
      witchcraft were reported. CONCLUSIONS: A train-the-trainer approach is a
      sustainable intervention that appears to have positive benefits on the health of
      village women living in Malawi, Africa.

PMID- 11308114
TI  - Development of a women's wellness center in Almaty, Kazakhstan.
AB  - Twelve Women's Wellness Centers were established by American International Health
      Alliance (AIHA) partnerships in the New Independent States of the former Soviet
      Union. The services offered by these centers focused on health promotion, disease
      prevention, and other health and social issues that affect women's health. The
      innovations in the model include patient-centered care that emphasizes patient
      choice and the introduction of the role of the nurse educator.

PMID- 11308115
TI  - Hispanic women's perceptions regarding cervical cancer screening.
AB  - OBJECTIVE: To examine factors affecting cervical cancer screening behaviors.
      DESIGN: Qualitative, descriptive. SETTING: Interviews were conducted in
      participants' homes. PARTICIPANTS: Purposive sample of 20 Hispanic women 18 to 65
      years of age. RESULTS: Participants accessed the health care system primarily
      during times of illness or in association with impending marriage, obtaining
      birth control, or childbearing. Barriers to screening participation included
      personal/cultural and provider/ system factors. Motivators included personal
      experience with others having cervical cancer, perceived importance of the Pap
      smear in maintaining health, reduction of financial barriers, and access to
      culturally appropriate health care. CONCLUSIONS: Factors affecting cervical
      cancer screening behavior among Hispanic women are identifiable and describable.
      Knowledge of barriers and motivators can be utilized to design effective nursing
      interventions and community-based programs.

PMID- 11308116
TI  - Availability of antidotes in hospital pharmacies in Greece.
AB  - We determined the availability of poisoning antidotes in the pharmacies of state
      hospitals in Greece and in Health Centers of the island of Crete. A questionnaire
      survey was sent to all pharmacy directors of hospitals with emergency
      departments, asking them to report anonymously the amount currently in stock of
      each of 12 common antidotes. Questionnaires were sent to 100 pharmacy directors
      and 68 (68%) of them replied. Only 2 (3%) of the 68 hospitals stocked all 12
      antidotes. The percentage of sufficient stocking for individual antidotes ranged
      from 6% (for digoxin immune fab) to 91% (for methylene blue). Recent circulation
      of government guidelines for antidote stocking and hospital type had no
      significant effect on antidote stocking. In a multiple regression analysis,
      hospital type (prefectural, regional, university hospital) and smaller hospital
      size were not predictors of the number of antidotes sufficiently stocked. Storing
      of key poisoning antidotes is inadequate in regional as well as in prefectural
      hospitals in Greece. Antidotes, including those which should be used without
      delay to be effective, are often not available, even for the commoner poisons in
      Greece such as pesticides.

PMID- 11308117
TI  - Does prolonged cyanide exposure have a diabetogenic effect?
AB  - Cyanide exposure through cassava consumption has been associated with the
      development of malnutrition-related diabetes mellitus (MRDM). However, there are
      few experimental reproductions of this disease. In the present study 42 rats
      received 0, 9.0 or 12.0 mg KCN/kg bw/d for 15 d, 26 pigs were dosed with 0, 2.0,
      4.0 or 6.0 mg KCN/kg for 74 d, and 34 goats received 0, 0.3, 0.6, 1.2 or 3.0 mg
      KCN/kg for 5 mo. At the end of each experimental period, plasma samples were
      obtained for glucose and thiocyanate measurement, and the pancreas was collected
      for histopathologic study. No significant differences in plasma glucose
      concentrations occurred between groups. The pancreas had no pathology. Chronic
      cyanide exposure did not promote diabetogenic effects in rats, swine or goats,
      suggesting that cyanide is not responsible for MRDM in humans.

PMID- 11308118
TI  - Fumonisin B1 carry-over into milk in the isolated perfused bovine udder.
AB  - The mycotoxin fumonisin B1 (FB1) causes a variety of health problems in animals,
      while epidemiological evidence suggests it is linked to human esophageal cancer.
      We investigated the carry-over of FB1 into bovine milk using the isolated
      perfused bovine udder. Two mg of FB1 was injected into the perfusion blood of 3
      udders, and milk and perfused serum levels were determined for 150 min. FB1
      passed through the mammary barrier into the milk, but in such low concentrations
      as to present a negligible risk for consumers.

PMID- 11308119
TI  - Management of anticoagulant poisoning.

PMID- 11308120
TI  - Keeping up-to-date: 1950-2001.

PMID- 11308121
TI  - Opportunities and challenges of strengthening veterinary toxicology in Africa in
      the 21st century.
AB  - Veterinary toxicology is the specialty of veterinary medicine dealing with the
      study, diagnosis and treatment of effects of natural and man-made chemicals,
      forms of energy, and gasses in the animal kingdom. Historically, veterinary
      toxicology has been narrowly defined as the diagnosis and treatment of poisoning
      in domesticated animals and poultry, but the profession has grown to include food
      safety and environmental toxicology. Veterinary toxicology is most well-developed
      and recognized as a specialty in North America where professional societies and
      specialty board certification exist. In many parts of Africa, perhaps with the
      exception of South Africa, veterinary toxicology has not evolved in more than 40
      years. The importance of veterinary toxicology in the modern era can not be over
      emphasized. This report examines the status of veterinary toxicology in Africa at
      the beginning of the 21st century and offers arguments why it is important for
      African governments to devote more resources to strengthen it.

PMID- 11308122
TI  - Combined toxicity of Cassia senna and Citrullus colocynthis in rats.
AB  - Body weight loss, inefficiency of feed utilization, diarrhea, ruffled hair and
      enterohepatonephrotoxicity were effects on male Wistar rats fed diet containing
      10% Cassia senna or 10% Citrullus colocynthis ripe fruits for 6w. Rats fed a 1:1
      mixture (5% + 5%) of fruits from these plants were more adversely affected and
      had deaths than rats fed the individual plants. The changes associated with the
      macrocytic hypochromic anemia and leukopenia were increased serum AST, ALT and
      ALP activities, increased urea, and decreased total protein, albumin and calcium.
      Serum bilirubin concentration did not change.

PMID- 11308123
TI  - The effects of sodium bicarbonate on thioridazine-induced cardiac dysfunction in
      the isolated perfused rat heart.
AB  - To determine the site of thioridazine-induced cardiotoxicity and investigate the
      effectiveness of sodium bicarbonate (NaHCO3) therapy, isolated rat hearts were
      perfused with Krebs-Henseleit-Bicarbonate buffer (KHB) at a constant coronary
      flow of 10 mL/min and electrically paced at 300 bpm. Experimental protocol
      included 15 min intervals of KHB, thioridazine (TDZ), TDZ + NaHCO3, KHB. Left
      ventricular (LV) pressure was measured with a balloon-tipped catheter placed in
      the LV via the mitral valve. Coronary perfusion pressure was monitored
      continuously as an index of coronary vascular resistance (CVR). LV generated
      pressure (LVGP) was used as our index of cardiac function and was calculated by
      subtracting LV end diastolic pressure (LVEDP) from LV peak systolic pressure
      (LVPSP). TDZ at 7,500 ng/mL was chosen as the toxic dose. NaHCO3 treatment was at
      an approximate sodium = 155 mM and pH = 7.60. Hearts perfused with TDZ resulted
      in a progressive decrease in LVGP. After 15 min of TDZ perfusion, LVGP decreased
      by 50%, and 75% at 30 min (n = 5). TDZ increased LVEDP and decreased LVPSP. TDZ
      perfusion increased CVR by 83%. In another experiment, hearts were perfused with
      TDZ for 15 min and then for an additional 15 min with TDZ + NaHCO3. NaHCO3
      treatment transiently (approximately 5 min) increased LVGP by 23% (n=5). During
      NaHCO3 treatment, LVPSP increased and LVEDP and CVR decreased during the first 5
      min. During the remainder of the NaHCO3 protocol, the hearts failed, similar to
      TDZ alone. TDZ diminished left ventricular function and promoted coronary artery
      vasoconstriction. NaHCO3 temporariy reversed these toxic effects.

PMID- 11308124
TI  - Effect of endosulfan on peripheral sheep leukocytes in vitro.
AB  - The immunotoxic and genotoxic effect of endosulfan, an organochlorine
      insecticide, on sheep peripheral blood leukocytes was examined in in vitro
      conditions. The immunotoxic effect was evaluated by assays of the metabolic
      activity of phagocytes and assays for lymphocyte activation--the leucocyte
      migration-inhibition assay (LMIA) and lympho-proliferation. The significant
      inhibitory effect of endosulfan on metabolic activity of peripheral blood
      phagocytes was registered at the actual concentrations of 10(-3)- 10(-4) M. At
      10(-3) M the migration of leukocytes was inhibited, both in activated and non
      activated with phytohemagglutinin (PHA) leukocyte suspensions (p < 0.01) in LMIA.
      This indicated the direct cytotoxic effect of endosulfan on the
      polymorphonuclears and monocytes of which the intensity of migration is an
      indicator of lymphocyte activation with mitogen. At the concentration of 10(-4) M
      an immunotoxic effect, ie significant decrease of lymphocyte activation with
      mitogen was recorded in LMIA. Lympho-proliferation test showed the significant
      inhibition of proliferation for PHA-stimulated lymphocytes at 10(-3) M and 10(-4)
      M. Micronucleus assay evaluated the genotoxic potential of endosulfan. Higher
      concentrations of insecticide (10(-5) M, 10(-6) M) resulted in a significant dose
      dependent increase in the number of micronuclei.

PMID- 11308125
TI  - The effect of zinc supplementation on antioxidant and lipid peroxidation status
      during Brachiaria decumbens intoxication in sheep.
AB  - An attempt was made to clarify the association between zinc (Zn) and antioxidants
      due to Zn supplementation on lipid peroxidation occurring during Brachiaria
      decumbens intoxication. The concentration of Zn, copper, malondialdehyde (MDA),
      superoxide dismutase (SOD), and gluthathione peroxidase (GSH-Px) were determined
      in tissues. There was a gradual increment in the concentration of Zn and MDA in
      serum and hepatocytic SOD in groups given Zn + B decumbens. A decline in
      erythrocytic GSH-Px and SOD, and lower concentration of reduced glutathione in
      hepatocyte cytosols were also detected in these sheep. It is highly suggestive
      that Zn supplementation may depress antioxidant status and enhance lipid
      peroxidation during B decumbens intoxication.

PMID- 11308126
TI  - Accumulative sodium poisoning in Brazilian swine fed whey.
AB  - Fifty 3-4-mo-old piglets died of accumulative sodium poisoning, but none of the
      60 adult pigs with the same feeding and management did. The average ambient
      temperature throughout the period was 32 C. The herd had been regulary fed whey,
      ground corn and vegetables, but for at least 2 d the pigs were deprived of water
      and then water was offered ad libitum. Twenty hours later 20 piglets had died and
      the remaining exhibited classical nervous signs and died within 14 h. Only the
      piglets had a high degree of dehydration caused by water deprivation and
      exacerbated by the high average ambient temperature. Pulmonary edema was evident
      in most piglets. Acute cerebral edema and meningoencephalitis were present in all
      animals, but there was no polioencephalomalacia. The sodium accumulation was
      caused by the continuing intake of whey which contained 10,810 mg sodium/L. To
      produce the whey, 2 kg of sodium chloride had been added to every 100 kg of milk.

PMID- 11308127
TI  - Two cases of ethylene dibromide poisoning.
AB  - Ethylene dibromide (EDB) is commonly available as a liquid pesticide for use as
      fumigant and preservative for storage of cereals and grains in India. Accidental
      or suicidal ingestion is often associated with often fatal delayed sudden hepatic
      or renal failure. We report 2 cases of EDB poisoning in humans.

PMID- 11308128
TI  - Lead poisoning in cattle and buffalo near primary lead-zinc smelter in India.
AB  - Varying degrees of lead (Pb) poisoning was recorded in cows and buffaloes near a
      primary lead-zinc smelter in India. Affected animals had history of clinical
      signs characterized by head pressing, violent movement, blindness and salivation.
      These animals revealed considerably high lead levels in blood (1.43 +/- 0.07 ppm)
      and milk (0.75 +/- 0.19 ppm). Animals from the same place without the history of
      clinical signs suggestive of Pb poisoning recorded lower blood Pb levels than the
      affected animals; however, their blood Pb was higher than that reported for
      cattle in rural and urban areas of India. Affected animals also carried high
      levels of cadmium (Cd) in blood (0.11 +/- 0.01 ppm) and milk (0.05 +/- 0.01 ppm).
      These values were considerably higher than those for rural cattle in India. The
      findings indicated varying degrees of exposure of animals to Pb and Cd in the
      vicinity of the smelter.

PMID- 11308129
TI  - Drought associated poisoning of cattle in South Texas by the high quality forage
      legume Leucaena leucocephala.
AB  - Approximately 80 head of yearling cattle grazing on 680 acres exhibited signs of
      Leucaena leucocephala toxicosis, which was confirmed in 3 animals by detection of
      3-hydroxy-4 (IH)-pyridone, the metabolite of the poisonous principle mimosine, in
      their urine. The animals had grazed leucaena almost exclusively due to lack of
      alternative forage resulting from drought conditions. Toxicosis from this
      otherwise high quality forage would likely not have occurred had animals consumed
      lower amounts of leucaena and could probably have been prevented, as it has been
      elsewhere, had the animals been colonized with Synergistes jonesii, a beneficial
      ruminal bacterium capable of degrading the toxic metabolites.

PMID- 11308130
TI  - Distribution of polychlorinated biphenyls in contaminated swine tissue.
AB  - In 1999 an accidental contamination of feed occurred in Belgium. This incident
      lead Authorities to increase monitoring levels of polychlorinated biphenyls (PCB)
      in food of animal origin. In our Department 220 samples of swine tissues, meat
      and adipose tissue, were analysed. The quantitation of PCB was made from the sum
      of 7 congeners obtained by gas chromatography with an electron capture detector.
      Confirmatory analysis was performed by gas chromatography/mass spectrometry. The
      PCBs in the majority of samples were close to the method limit of detection and
      only a few samples had PCB concentrations > the limit of quantitation. In those
      tissues the average concentration of PCBs was 0.035 mg/kg. The legal limit of
      0.200 mg PCB/kg established by the European Union was exceeded by only 1 sample,
      a smoked ham from Belgium. This sample showed the presence of all selected
      congeners. We report the profile of the PCB congeners in this sample.

PMID- 11308131
TI  - Ecstasy ingestion and fulminant hepatic failure: liver transplantation to be
      considered as a last therapeutic option.
AB  - Severe adverse effects due to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
      are reported with increasing frequency in the medical literature. The signs of
      acute toxicity most often seen are fulminant hyperthermia, hyperexcitatory
      states, acute renal failure and hyponatraemia. In 1992, hepatotoxicity was also
      described with unexplained jaundice and hepatomegaly after ingestion of MDMA. We
      report a case of severe toxic hepatitis following ingestion of MDMA with
      fulminant hepatic failure which required auxiliary liver transplantation. The
      diagnosis was necrotic toxic hepatitis following ecstasy ingestion. The outcome
      was successful, and the patient was discharged from ICU 20 d after surgery.
      Hepatotoxic effects of MDMA seem infrequent, but may be lethal; liver
      transplantation is the ultimate therapeutic option in some cases.

PMID- 11308132
TI  - Cutaneous lupus erythematosus.
AB  - Lupus erythematosus (LE) has many different clinical manifestations including a
      variety of cutaneous findings. Some of the cutaneous manifestations are not
      specific for LE, such as photosensitivity reactions, oral ulcers, alopecia,
      urticaria, vasculitis, vesiculo-bullous lesions, acral changes, cutaneous
      mucinoses, and cutaneous calcinosis. Other findings are specific for LE in that
      they are found only in patients who have lupus erythematosus. These LE-specific
      disorders include acute cutaneous LE, subacute cutaneous LE, and several forms of
      chronic cutaneous LE, including discoid LE. Skin biopsies are often helpful in
      differentiating LE-specific skin lesions from other disorders that can mimic
      them. Photoprotective measures and a number of drugs are useful in treating
      cutaneous LE.

PMID- 11308133
TI  - Antinuclear antibodies in dermatology.
AB  - Antinuclear antibodies are used in the diagnosis and evaluation of patients with
      connective tissue diseases. The study of antinuclear antibodies has also
      fundamentally expanded our understanding of nuclear anatomy and function. This
      article reviews the clinically relevant antinuclear antibodies and their disease
      associations. Developing an understanding of the utilities and limitations of
      antinuclear antibodies is essential to providing the expert diagnoses prognoses,
      and care expected of a dermatologist.

PMID- 11308134
TI  - Localized and systemic scleroderma.
AB  - Scleroderma is a broad term encompassing both localized and systemic sclerosis.
      Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque
      morphea, generalized morphea, linear scleroderma, and deep morphea. Systemic
      scleroderma (sclerosis) can manifest as either limited or diffuse disease.
      Limited systemic sclerosis is typically preceded by Raynaud's phenomenon,
      involves cutaneous sclerosis distal to the elbows, with gastrointestinal and
      pulmonary fibrosis, and anticentromere antibody positivity. Diffuse systemic
      scleroderma is characterized by simultaneous Raynaud's phenomenon, cutaneous skin
      involvement proximal to the elbow with gastrointestinal, pulmonary, renal and
      cardiac fibrosis, and positive serology for antitopoisomerase and anti-RNAP III
      antibodies. This article discusses the classification, epidemiology,
      pathogenesis, clinical manifestations, treatment, and prognosis of the
      scleroderma.

PMID- 11308135
TI  - Dermatomyositis.
AB  - Dermatomyositis is a disease that has a characteristic skin eruption that may
      occur with or without a proximal myopathy. The disease with cutaneous features
      only is classified as amyopathic dermatomyositis. The origin is unknown, but
      autoimmune factors are believed to play an important role. Autoantibodies are
      found in most patients and some have myositis-specific antibodies. Systemic
      changes may occur and there appears to be a relationship to internal malignancy,
      particularly in older patients. Juvenile disease has an associated vasculopathy.
      Treatment includes systemic corticosteroids and other immunosuppressive agents.
      The cutaneous changes may be difficult to treat.

PMID- 11308136
TI  - Sjogern's syndrome.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune exocrinopathy that affects the
      salivary and lacrimal glands. It typically presents as the "sicca complex" of dry
      eyes (xerophthalmia) and dry mouth (xerostomia) along with other symptoms such as
      arthritis. SS is classified as either primary or secondary. In the primary form,
      dry eyes and dry mouth occur alone. In the secondary form, the dry eyes and dry
      mouth occur in the context of another rheumatic disease, most commonly rheumatoid
      arthritis. There is an increasing list of systemic manifestations affecting the
      lung, kidney, and nervous system in patients with SS. The skin is affected in
      half of SS patients. Despite this high frequency of cutaneous involvement,
      patients with SS are not commonly seen in dermatology practices. SS is
      underrecognized and underdiagnosed because the cutaneous manifestations are
      nonspecific (eg, xerosis, pruritus) and less severe than the oral, ocular, or
      musculoskeletal symptoms. Nonetheless, because of its high prevalence, risk of
      cutaneous vasculitis, and the increased risk of a lymphoproliferative disorder,
      it is important for dermatologists to be familiar with SS.

PMID- 11308137
TI  - Behcet disease.
AB  - Behcet's disease is a multisystem inflammatory disorder of unknown origin,
      characterized by recurrent oral and genital ulcerations, ocular and cutaneous
      lesions, arthritis, central nervous system, and vascular disease. There is no
      pathognomonic laboratory test, but there are clinical criteria to assist in
      establishing the diagnosis. Behcet's is most common along the Silk Road. It is
      particularly common among persons who have the HLA-B51 major histocompatibility
      type. Cutaneous lesions include pustules, erythema nodosum-like lesions, Sweet's
      like lesions, pyoderma gangrenosum-ike lesions, and pathergy. The major cutaneous
      findings may be classified as neutrophilic vascular reactions. There is
      considerable morbidity resulting from Behcet's disease, most notably a high risk
      of blindness from ocular involvement. Mortality may occur as a result of
      neurologic or vascular disease or gastrointestinal perforation.

PMID- 11308138
TI  - Immunosuppressive and cytotoxic drugs in the treatment of rheumatic skin
      disorders.
AB  - Cytotoxic and immunosuppressive drugs are regularly used to treat proliferative,
      immunologically mediated inflammatory disorders and some neoplastic diseases of
      the skin. Methotrexate, azathioprine, mycophenolate mofetil, cyclosporin
      cyclophosphamide, chlorambucil, and other related drugs have potential benefits
      in the treatment of severe and/or recalcitrant rheumatic skin diseases. The
      therapeutic window for these agents is narrow. The major uses of these drugs are
      for life-threatening cutaneous disorders or as steroid-sparing agents.

PMID- 11308139
TI  - CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in
      staging esophageal cancer.
AB  - BACKGROUND: The staging of esophageal cancer is imprecise.
      Thoracoscopic/laparoscopic (TS/LS) staging has been proposed as a more accurate
      lymph node (LN) staging method. We report the experience of an Intergroup NCI
      trial (CALGB 9380) evaluating the feasibility and accuracy of this staging
      modality. PATIENTS AND METHODS: From February 1995 to September 1999, 134
      patients were entered in the study. This study represents the analysis of final
      data on 113 patients. TS/LS was considered feasible if TS and 1 LN sampled at
      least 3 LN by LS; a confirmed positive node was found; or T4 or M1 disease was
      documented. If this was accomplished in more than 70% of patients, TS/LS was
      believed to be feasible. RESULTS: The LN stations most frequently sampled in the
      thorax (134 patients) were levels 2 (33%), 3 (38%), 4 (40%), 7 (76%), 8 (69%), 9
      (55%), and 10 (43%) and in the abdomen levels 17 (70%) and 20 (55%). The
      frequency of positive LN by level were as follows: 2 (10%), 3 (8%), 4 (10%), 7
      (10%), 8 (25%), 9 (10%), 10 (10%), 17 (34%), and 20 (27%). Noninvasive tests
      (computed tomographic scan, magnetic resonance imaging, esophageal ultrasound
      scan) each incorrectly identified TN staging as noted by missed positive or false
      negative LN or metastatic disease found at TS/LS staging in 50%, 40%, and 30% of
      patients, respectively. Median operating time was 210 minutes (range, 40 to 865
      minutes). Median postoperative hospital stay was 3 days (range, 1 to 35 days).
      There were no deaths or major complications. Seventy-three percent of patients
      met the definition for feasibility. In 30 patients TS was not feasible. Positive
      LN disease was found in 43 patients; 32 were deemed N0. Ten patients had T4/M1
      disease. Of the 32 potentially resectable N0 patients, 14 patients had
      preoperative induction therapy; 13 patients went directly to operation with N0
      confirmed in 9 patients, NX in 1 and N1 in 3. Three patients were unresectable, 1
      patient died, and 1 was lost to follow-up. CONCLUSIONS: In summary, the
      feasibility of TS/LS was confirmed. It doubled the number of positive LNs
      identified by conventional, noninvasive staging. The overall accuracy remains to
      be defined by analysis of the LN negative group in follow-up. Although the
      positive predictive value was high, further study is warranted to confirm the
      role of TS/LS in the staging algorithm of esophageal cancer.

PMID- 11308140
TI  - Laparoscopic management of giant paraesophageal herniation.
AB  - BACKGROUND: Many surgeons have found laparoscopic fundoplication effective
      management of medically recalcitrant gastroesophageal reflux disease (GERD)
      associated with sliding type I hiatal hernias. The anatomic distortion and
      technical difficulty inherent with repair has limited the use of laparoscopy for
      repair of "giant" paraesophageal hernias (gPH). METHODS: Since July 1993, we have
      accomplished laparoscopic repair of paraesophageal hiatal hernias in 54 of 60
      (90%) patients. Five patients had classic type II hernias with total
      intrathoracic stomachs, and 53 patients had large sliding/paraesophageal type III
      herniation. Two patients had true parahiatal hernias. None had gastric
      incarceration. Median age was 53 years and 28 of 60 (47%) were women. Chest pain
      and dysphagia were primary complaints from 39 of 60 (65%). Heartburn with or
      without regurgitation was present in 52 of 60 (85%). Preoperative manometry and
      prolonged pH testing were obtained on 43 of 60 (72%) and 44 of 60 (73%) patients,
      respectively. Principles of repair included reduction of the hernia, excision of
      the sac, crural approximation, and fundoplication over a 54F bougie (Nissen, 41;
      Dor, 1; Toupet, 18) to "pexy" the stomach within the abdomen and to control
      postoperative reflux. RESULTS: Mean operative time was 202+/-81 minutes.
      Conversion to "open" repair was required in 6 patients (iatrogenic esophageal
      injury in 2 patients and difficult hernia sac dissection in 4 patients). One
      postoperative mortality occurred as a result of sepsis and multiorgan failure
      after an intraoperative esophageal perforation. Follow-up barium swallow
      performed in 44 of 60 patients demonstrated recurrent hiatal hernias in 3
      patients. Preoperative symptoms have been relieved in all but 3 patients.
      Reoperation for recurrent paraesophageal herniation has been required in these
      latter 3 patients. CONCLUSIONS: Although technically challenging, laparoscopic
      repair of paraesophageal hiatal hernias is a viable alternative to "open"
      surgical approaches. Control of the herniation and the patient's symptoms are
      equivalent and hospitalization and return to full activity are shorter.

PMID- 11308141
TI  - Visceral pleura invasion by non-small cell lung cancer: an underrated bad
      prognostic factor.
AB  - BACKGROUND: Visceral pleura invasion (VPI) by non-small cell lung cancer is a
      factor of poor prognosis. A tumor of any size that invades the visceral pleura is
      classified as T2. Few studies have been conducted concerning the prognostic
      significance of VPI relative to other staging factors. METHODS: Between April
      1984 and December 1996, 1,281 patients with T1 (n = 430) and T2 (n = 851) non
      small cell lung cancer underwent curative surgical resection. Adjuvant radiation
      therapy was performed in 455 patients. There were 176 women and 1,105 men aged 30
      to 86 years (mean, 60.9 years). Five hundred nineteen pneumonectomies, 742
      lobectomies, and 20 segmentectomies were performed. In all patients, a complete
      mediastinal lymph node dissection was performed. International staging was stage
      IA and B (n = 697); stage II A and B (n = 247), and stage III A (n = 337). The
      patients were divided into two groups according to the existence of VPI (group I
      without, group II with). Both groups were compared with regard to the size of the
      tumors, histology, associated lymph node involvement, survival rates, and cause
      of death. Univariate and multivariate analyses were conducted. RESULTS: VPI
      (group II) was identified in 19.1% of the resected specimens: group I, n = 1036;
      group II, n = 245. The VPI was present in only 10% of non-small cell lung cancer
      3 cm or less in size, reaching 33% of patients with non-small cell lung cancer
      larger than 5 cm (p = 0.0001). Squamous non-small cell lung cancer were
      significantly less accompanied by VPI (13.5%) than the other histologic
      categories. The VPI was associated with a higher frequency of N2 involvement
      (group I = 24.6%, group II = 33.4%, p = 0.01) and N2 involvement was more
      extensive (two or more N2 involved stations: group I = 8.2%, group II = 15.6%, p
      = 0.003). Actuarial survival rates were 51.8% at 5 years and 33.8% at 10 years in
      group I (median, 66 months), and 34.6% at 5 years and 27.9% at 10 years in group
      II (median, 30 months) (p = 0.000002). Long-term survival rates significantly
      decreased for larger tumors. Even in patients with N2 stage tumors, the
      difference of survival curves between the two groups was statistically
      significant. Cancer-related deaths were more frequent in group II and were mainly
      caused by distant metastases. By multivariate analysis, visceral pleura invasion
      proved to be a significant independent factor of poor prognosis. CONCLUSIONS: The
      VPI is a factor of poor prognosis. Its frequent association with extensive N2
      involvement supports the hypothesis that exfoliated tumor cells are drained
      through the pleural lymphatics by the mediastinal lymphatic pathways and then
      into the bloodstream. The VPI is an important prognostic factor and, as such
      should stimulate more studies to better select the patients who could benefit
      from adjuvant therapy.

PMID- 11308142
TI  - Surgical treatment of lung cancer invading the chest wall: results and prognostic
      factors.
AB  - BACKGROUND: The study was performed to assess prognostic factors in patients with
      lung cancer invading the chest wall treated by surgery. METHODS: We reviewed
      retrospectively clinical records of all patients operated on for lung cancer
      invading chest wall structures between 1984 and 1998. RESULTS: Two hundred one
      patients were operated on in this 14-year period. One hundred thirty-seven
      lobectomies, 55 pneumonectomies, and 9 wedge resections were performed.
      Extrapleural resection (when invasion was limited to the parietal pleura) and
      chest wall resection (in the case of invasion of deeper structures) were combined
      with pulmonary resection in 79 (39%) and 122 (61%) cases, respectively.
      Pathologic TNM stages were T3N0 in 116 (57.5%) cases, T3N1 in 52 (26%), T3N2 in
      27 (13.5%), and T4N0-N1 in 6 (3%). A complete resection was achieved in 167 (83%)
      cases. Fourteen postoperative deaths (7%) occurred. One hundred thirty-nine
      patients (74%) underwent postoperative radiotherapy. Actuarial 5-year survival
      was 24% and 13% after complete and incomplete resection, respectively (p < 0.05).
      Actuarial 5-year survival after complete resection was 25% in T3N0 patients, 20%
      in T3N1, and 21% in T3N2. In completely resected patients, univariate and
      multivariate analyses identified three independent prognostic factors: nodal
      involvement, depth of parietal invasion, and age. Radiation therapy did not
      improve survival if a complete resection was possible. CONCLUSIONS: Completeness
      of resection, nodal involvement, depth of invasion, and age affect survival of
      patients with lung cancer invading the chest wall. N2 disease should not be
      considered a contraindication to surgery.

PMID- 11308143
TI  - Segmentectomy for roentgenographically occult bronchogenic squamous cell
      carcinoma.
AB  - BACKGROUND: Roentgenographically occult bronchogenic squamous cell carcinomas
      (ROSCCs) are early squamous cell lung cancers of central type. Some of them
      cannot be treated with intrabronchial therapy. Although surgical treatment was
      performed for such tumors, it was unknown whether lobectomy was indispensable or
      not. METHODS: The clinicopathologic information of the 58 patients who underwent
      segmentectomy for ROSCCs were collected from 16 hospitals and reviewed
      retrospectively, compared with 98 patients who underwent lobectomy for ROSCCs.
      RESULTS: Five-year survival rate of the 58 patients based on lung cancer deaths
      was 96.8%, and 82.6% including all causes of death. The duration of chest tube
      drainage in the segmentectomy group was slightly longer than in the lobectomy
      group. Operative mortality and the frequency of postoperative complications were
      not statistically different in both groups. Postoperative/preoperative vital
      capacity and forced expiratory volume in 1 second were higher in the
      segmentectomy group. CONCLUSIONS: These results suggest that segmentectomy may be
      an alternative for surgical therapy of carefully selected ROSCCs. More
      prospective studies are required to fully demonstrate clinical benefit.

PMID- 11308144
TI  - Preoperative chemotherapy for lung cancer does not increase surgical morbidity.
AB  - BACKGROUND: Preoperative chemotherapy (C+S) for non-small cell lung cancer
      (NSCLC) has increased in an attempt to improve survival. Patients receiving C+S
      potentially may have an increase in postoperative morbidity and mortality
      compared with surgery alone (S). We reviewed our experience with C+S and S in a
      tertiary referral center. METHODS: Three hundred eighty consecutive patients
      underwent lobectomy or greater resection for NSCLC between August 1, 1996, and
      April 30, 1999: 335 patients (259 S; 76 C+S) were analyzed; 45 additional
      patients were excluded for prior NSCLC, other chemotherapy for other malignancy,
      or radiation. We compared morbidity and mortality overall, and by subset analysis
      (clinical stage, pathological stage, procedure, and by protocol use) for both C+S
      and S patients. RESULTS: Demographics, comorbidities, and spirometry were
      similar. We noted no significant difference in overall or subset mortality or
      morbidity including pneumonia, acute respiratory distress syndrome, reintubation,
      tracheostomy, wound complications, or length of hospitalization. CONCLUSIONS: C+S
      did not significantly affect morbidity or mortality overall, based on clinical
      stage, postoperative stage, or extent of resection. The potential for enhanced
      survival in resectable NSCLC justifies continued study of C+S.

PMID- 11308145
TI  - Open lung biopsy as an outpatient procedure.
AB  - BACKGROUND: Lung biopsies are frequently needed to diagnose diffuse interstitial
      lung diseases. Both limited thoracotomy (open lung biopsy) and thoracoscopy can
      be used for lung biopsies, but both procedures have traditionally required
      hospital admission. We report a series of patients that underwent outpatient open
      lung biopsy to show the safety and effectiveness of this practice. METHODS: We
      reviewed records of ambulatory, nonoxygen dependent patients with a clinical
      diagnosis of diffuse interstitial lung disease that underwent outpatient open
      lung biopsy between January 1997 and December 1999. All procedures were done by a
      senior surgeon using single lumen endotracheal anesthesia, a small anterolateral
      thoracotomy without rib spreading, stapled wedge resection, and no chest tube.
      Patients were discharged the same day. RESULTS: Thirty-two patients with a
      clinical diagnosis of diffuse interstitial lung disease underwent outpatient open
      lung biopsy. Mean age was 58 years (range, 21 to 74 years). Preoperative forced
      expiratory volume in 1 second was 74.3%+/-7.0% of predicted. A pathologic
      diagnosis was established in all patients: usual interstitial pneumonia, 26
      patients; sarcoidosis, 2; metastatic carcinoma, 2; desquamative interstitial
      pneumonia, 1; and mixed dust pneumoconiosis, 1 patient. No patient required a
      chest tube, overnight observation, or hospital admission. No complications
      occurred. CONCLUSIONS: Selected patients with a clinical diagnosis of diffuse
      interstitial lung disease can safely and effectively undergo diagnostic
      outpatient open lung biopsy. However, careful patient selection and attention to
      operative detail are essential.

PMID- 11308146
TI  - Early complications of thoracic endoscopic sympathectomy: a prospective study of
      940 procedures.
AB  - BACKGROUND: Thoracic endoscopic sympathectomy (TES) has become the surgical
      technique of choice for treating intractable palmar hyperhidrosis and is usually
      considered as a simple and safe procedure. To evaluate the complication rate of
      TES, we conducted a prospective study of peri- and postoperative complications.
      METHODS: From 1995 to 1999, 467 consecutive patients were operated on for upper
      limb hyperhidrosis. There were 164 men and 303 women, ranging in age from 15 to
      59 years (mean 31 years). In all but 5 cases, the procedure was bilateral. Eleven
      patients underwent a reoperation for failure; thus the total number of
      sympathectomies was 940. The procedure was performed in two stages in 182
      patients and in one stage in 267 patients. All patients were seen 1 month after
      the operation. RESULTS: There was no mortality. The mean postoperative hospital
      stay was 2.3 days in the group of patients who were operated on in two stages and
      1.1 day in patients who were operated on in one stage. There were three major
      complications: one tear of the right subclavian artery and two chylothoraces.
      There were 25 cases (5.3%) of bleeding (300 to 600 mL) during dissection of the
      sympathetic trunk due to injury to an intercostal vein; in all cases it was
      controlled thoracoscopically. There were 12 pneumothoraces (1.3%) after removal
      of chest tubes. All of these were unilateral. Four required chest drainage for a
      period of less than 24 hours. One patient had a mild pleural effusion. Four
      patients had a unilateral partial Horner Syndrome (0.4%) that disappeared within
      3 months in 2 patients. The other 2 patients were lost to follow-up. One patient
      complained of rhinitis. CONCLUSIONS: Although morbidity was low, significant
      complications of TES occurred. Patients should be clearly warned that TES is not
      as minor a procedure as usually asserted. Complications as well as adverse
      effects should be considered when discussing this surgical indication.

PMID- 11308147
TI  - Validation of an orthotopic model of human lung cancer with regional and systemic
      metastases.
AB  - BACKGROUND: We developed an orthotopic model of human lung cancer that exhibits
      highly predictable regional and systemic metastases. This study examines the
      response of the model when treated with conventional and experimental
      chemotherapy. METHODS: NCI-H460 tumor fragments were implanted into the right
      caudal lung lobe of a nude rat. Treatment commenced 2 weeks later. We assessed
      response by comparing primary tumor and mediastinal lymph node weights, total
      body weight, and length of survival with untreated, tumor-bearing control
      animals. We also calculated the incidence of metastasis to kidney, bone, brain,
      and contralateral lung in treated versus untreated animals. RESULTS: Mitomycin
      and cisplatin showed broad activity against primary and metastatic disease. The
      matrix metalloproteinase inhibitor batimastat, low-dose cisplatin, and mitomycin
      significantly prolonged survival. High-dose cisplatin caused renal toxicity that
      shortened survival. Brain metastases did not respond to mitomycin, consistent
      with its poor blood-brain barrier penetration. CONCLUSIONS: Responses were
      similar to NCI-H460 in vitro data and consistent with clinical experience for
      these drugs. Drug-related toxicities similar to those seen in clinical practice
      were detected.

PMID- 11308148
TI  - Endobronchial transfection of naked viral interleukin-10 gene in rat lung
      allotransplantation.
AB  - BACKGROUND: Recent studies suggest that viral interleukin-10 (vIL-10) suppresses
      alloimmune response in transplantation. Tissue mRNA expression of inducible
      nitric oxide synthase (iNOS) and exhaled nitric oxide (NO) levels have been
      observed to increase in lung allograft rejection. The aims of this study were to
      examine the feasibility of vIL-10 gene transfer into rat lung allografts and to
      investigate its effect on subsequent allograft rejection. METHODS: Male Lewis
      rats (RT1l) underwent left lung transplantation with allografts from Brown Norway
      rats (RT1n). The donor rats were endobronchially transfected 2 minutes before
      harvest with 400 microg (group I, n = 5), 600 microg (group II, n = 5), or 800
      microg (group III, n = 5) of naked pCMVievIL-10. Group IV (n = 5) animals,
      serving as control, received 400 microg of naked pCF1-CAT. All recipients were
      sacrificed on postoperative day 5. Transgene expression of vIL-10 was assessed by
      both reverse transcriptase-polymerase chain reaction and immunohistochemistry.
      Allograft gas exchange, exhaled NO level, histologic rejection score, and mRNA
      expression of graft cyokines were also assessed. RESULTS: Transgene expression of
      lung graft vIL-10 was detected by both reverse transcriptase-polymerase chain
      reaction and immunohistochemistry. The iNOS mRNA expression in groups I, II, and
      III was significantly lower than that of group IV (p < 0.05, analysis of
      variance). Exhaled NO levels in groups I, II, and III were significantly lower
      than in group IV (p < 0.01, analysis of variance). There was no significant
      difference between groups with respect to gas exchange, peak airway pressure, or
      histologic rejection score. CONCLUSIONS: It appears that endobronchial
      transfection of naked vIL-10 plasmid in a rat lung allotransplant model is
      feasible and suppresses lung iNOS mRNA expression and exhaled NO levels. An
      association between iNOS upregulation and high exhaled NO levels in lung
      allograft resection was also noted.

PMID- 11308149
TI  - Pulmonary macrophages are involved in reperfusion injury after lung
      transplantation.
AB  - BACKGROUND: Reperfusion injury is a perplexing cause of early graft failure after
      lung transplantation. Although recipient neutrophils are thought to have a role
      in the development of reperfusion injury, some researchers have shown that
      neutrophils are not involved in its earliest phase. Intrinsic donor pulmonary
      macrophages may be responsible for this early phase of injury. Using the
      macrophage inhibitor gadolinium chloride, we attempted to investigate the role of
      pulmonary macrophages in reperfusion injury after lung transplantation. METHODS:
      Using our isolated, ventilated, blood-perfused rabbit lung model, all groups
      underwent lung harvest followed by 18-hour storage (4 degrees C) and blood
      reperfusion for 30 minutes. Group I served as a control. Group II received
      gadolinium chloride at 7 mg/kg 24 hours before harvest. Group III received
      gadolinium chloride at 14 mg/kg 24 hours before harvest. RESULTS: Group III had
      significantly improved arterial oxygenation and pulmonary artery pressures
      compared with groups I and II after 30 minutes of reperfusion. CONCLUSIONS: The
      earliest phase of reperfusion injury after lung transplantation involves donor
      pulmonary macrophages.

PMID- 11308150
TI  - Raffinose improves 24-hour lung preservation in low potassium dextran glucose
      solution: a histologic and ultrastructural analysis.
AB  - BACKGROUND: We have previously shown that the addition of raffinose to low
      potassium dextran (LPD) preservation solution improves transplanted rat lung
      function after 24 hours of storage. The mechanisms by which raffinose acts are
      unclear. The aim of this study was to examine the histologic and ultrastructural
      correlates of this enhanced pulmonary function after preservation with raffinose.
      METHODS: In a randomized, blinded study, rat lungs were flushed with LPD, or LPD
      containing 30 mmol/L of raffinose, and stored for 24 hours at 4 degrees C.
      Control lungs were flushed with LPD but not stored (n = 5 each group). Changes in
      postpreservation edema were determined. In addition, lungs were flushed with a
      trypan blue solution to quantify cell death, and examined using both light and
      electron microscopy. RESULTS: The LPD lungs gained significantly more weight
      (25.5%+/-5.5%) compared with raffinose-LPD lungs (5.2%+/-5.3%; p < 0.0001). There
      were higher percentages of dead cells in the LPD lungs (29%+/-0.3% of total
      cells) compared with raffinose-LPD lungs (14%+/-1.4%; p < 0.001) and control
      lungs (0.2%+/-5%; p < 0.001). Control lungs maintained normal ultrastructure,
      whereas LPD lungs showed a decreased number of intact type II pneumocytes and
      significant cellular necrosis. Interstitial and alveolar edema with interstitial
      macrophage infiltration was also observed. Alveolar capillaries were collapsed.
      In contrast, raffinose-LPD lungs showed only mild alterations such as minimal
      interstitial edematous expansion, fewer damaged cells, and minimal capillary
      injury. CONCLUSIONS: Raffinose exerts a cytoprotective effect on pulmonary grafts
      during preservation, which explains the previously documented improved function.
      This simple modification of LPD with raffinose may provide clinical benefit in
      extended pulmonary preservation.

PMID- 11308151
TI  - Mitral valve procedure in dilated cardiomyopathy: repair or replacement?
AB  - BACKGROUND: Mitral valve (MV) procedure for dilated cardiomyopathy is becoming
      popular. We analyzed the indications to MV repair or replacement according to our
      10-year experience. METHODS: From January 1990 to May 2000, 49 patients with
      dilated cardiomyopathy (12 idiopathic and 37 ischemic) underwent MV operation, 29
      repair and 20 replacement. Preoperative evaluation included measurement of MV
      coaptation depth (CD) as a mirror of the abnormalities of MV apparatus leading to
      functional mitral regurgitation. RESULTS: Thirty-day mortality was 4.2% (2
      patients). One-, 3-, 5-, and 10-year actuarial survival was, respectively, 90%,
      87%, 78%, and 73%. The possibility of survival with at least one New York Heart
      Association functional class improvement was 88%, 76%, 71%, and 65%. Return of
      functional mitral regurgitation after MV repair was nearly inevitable; however,
      using a scale from 0 to 4, mean postoperative functional mitral regurgitation was
      1.2+/-0.8 when preoperative MVCD was 10 mm or less and 2.5+/-0.7 when
      preoperative MVCD was 11 mm or higher (p < 0.05). Globally, functional results
      were not influenced by the strategy of treatment (MV repair or replacement).
      CONCLUSIONS: Mitral valve operation can give satisfying survival and good
      palliation of dilated cardiomyopathy. The MVCD can be helpful in the choice of
      the surgical strategy on the MV.

PMID- 11308152
TI  - Change of c-Myc expression and cardiac hypertrophy in patients with aortic valve
      replacement.
AB  - BACKGROUND: Long-term volume overload to the left ventricle (LV) due to aortic
      regurgitation (AR) tends to cause severe impairment in LV function that cannot be
      reversed even with aortic valve replacement (AVR). Recently, we reported that the
      protooncogene c-myc is related to the onset of the cardiac hypertrophy and LV
      dysfunction in patients with chronic AR. However, it is still unclear whether c
      myc is related to reversibility of the cardiac hypertrophy or LV dysfunction
      after AVR. METHODS AND RESULTS: Twenty patients with isolated chronic AR who
      underwent AVR were included in this study. LV function was calculated before and
      after AVR. After AVR, end-systolic volume index (ESVI) and enddiastolic volume
      index (EDVI) were improved, but not mass index (LVMI). However, normalization of
      ESVI and EDVI was observed only in 12 and 9 patients, respectively.
      Preoperatively, c-Myc protein was expressed in the myocardium of 16 out of 20
      patients with an average point count of 35+/-30%. After AVR, c-Myc protein was
      observed only in 2 patients. Preoperative ejection fraction (EF), ESVI, and
      postoperative end-systolic stress (ESS)/ESVI had significant correlation to
      postoperative cell diameter (CD). Percent c-Myc protein expression before the
      operation was significantly correlated to postoperative CD, ESVI, and ESS/ESVI.
      Average c-Myc expression was higher in patients who showed normalization of CD
      and ESS/ESVI after AVR than the patients who did not. CONCLUSIONS: These data
      suggest that preoperative expression of c-Myc can be indicative of the
      reversibility of myocardial cellular hypertrophy and LV dysfunction.

PMID- 11308153
TI  - Surgical treatment of Brucella endocarditis.
AB  - BACKGROUND: Brucella endocarditis (BE) is a lethal complication of human
      brucellosis, which is rarely seen and hardly described. METHODS: In the present
      report, six successfully treated cases of BE involving three native aortic
      valves, two native mitral-aortic valves, and a mitral bioprosthesis are
      described. The diagnosis of BE was based on clinical features, high brucella
      serologic titers, and positive blood cultures. Although the blood cultures were
      positive in all patients, all the resected valve materials and tissue cultures
      were negative. The patients received rifampicin, streptomycin, and doxycycline
      (in 3 patients), rifampicin, tetracycline, and cotrimoxazole (in 2 patients), and
      rifampicin, doxycycline, and cotrimoxazole (in 1 patient). Infected native valves
      and bioprosthesis were replaced by mechanical valves. RESULTS: There was no early
      or late mortality. No recurrent infection developed after management with a
      combination of antibiotherapy lasting 6 months postoperatively during a mean
      follow-up of 47 months (range 20 to 84 months). CONCLUSIONS: This report suggests
      that the combination of valve replacement and antibiotic therapy produces
      successful results in the treatment of BE.

PMID- 11308154
TI  - Treatment of endocarditis with valve replacement: the question of tissue versus
      mechanical prosthesis.
AB  - BACKGROUND: It remains unknown whether there is any important clinical advantage
      to the use of either a bioprosthetic or mechanical valve for patients with native
      or prosthetic valve endocarditis. METHODS: Between 1964 and 1995, 306 patients
      underwent valve replacement for left-sided native (209 patients) or prosthetic
      (97 patients) valve endocarditis. Mechanical valves were implanted in 65
      patients, bioprostheses in 221 patients, and homografts in 20 patients. RESULTS:
      Operative mortality was 18+/-2% and was independent of replacement valve type (p
      > 0.74). Long-term survival was superior for patients with native valve
      endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve
      endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve
      type (p > 0.27). The long-term freedom from reoperation for patients who received
      a biologic valve who were younger than 60 years of age was low (51+/-5% at 10
      years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom
      from reoperation with a biological valve (84+/-7% at 15 years) was similar to
      that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64).
      CONCLUSIONS: Mechanical valves are most suitable for younger patients with native
      valve endocarditis; however, tissue valves are acceptable for patients greater
      than 60 years of age with native or prosthetic valve infections and for selected
      younger patients with prosthetic valve infections because of their limited life
      expectancy.

PMID- 11308155
TI  - Repeated thromboembolic and bleeding events after mechanical aortic valve
      replacement.
AB  - BACKGROUND: The choice of a valve substitute in young adults requires a decision
      balancing the risks of long-term anticoagulation versus reoperation(s). This
      article analyzes the long-term risk and determinants of thromboembolic (TE) and
      bleeding (BLE) complications after mechanical aortic valve replacement (AVR).
      METHODS: From December 1963 to January 1974, 249 patients survived a mechanical
      AVR at our institution. Mean age was 41.8+/-12.4 years and 81% (n = 202) were
      male. Ball valves were implanted in 24% (n = 61) and disc valves in 76% (n =
      188). Patients were anticoagulated with vitamin K antagonists and dipyridamole. A
      total of 4,855 patient-years was available for analysis. Mean follow-up was
      19.5+/-9.4 years and was 100% complete. Analyses were performed with Kaplan-Meier
      and multivariable Cox regression methods. RESULTS: One hundred and two patients
      had one TE or BLE postoperative event and 58 patients had two postoperative
      events. Six patients had more than five postoperative events. Freedom from a
      first postoperative event was 74.8%+/-2.9%, 55.3%+/-3.5%, and 46.8%+/-4.0% at 10,
      20, and 30 years, respectively. Freedom from a second postoperative event was
      45.4%+/-5.4%, 29%+/-6.0%, and 23.2%+/-7.1% at 10, 20, and 30 years, respectively.
      Multivariate predictors for TE or BLE complications were ball valve (Odds Ratio
      (OR) = 2.9), postoperative endocarditis (OR = 2.2), and any surgery (OR = 2.2).
      The incidence of events was highest the first 5 postoperative years. CONCLUSIONS:
      The risk of adverse events is highest the first 5 postoperative years. Once an
      event has occurred, the risk for a second event is increased. The incidence and
      frequency of events is substantial and should be considered in the choice of a
      valve substitute.

PMID- 11308156
TI  - Intermediate-term results with 1,019 carbomedics aortic valves.
AB  - BACKGROUND: A retrospective study was conducted to evaluate the intermediate-term
      outcome in patients with the Carbomedics aortic valve prosthesis. METHODS: The
      study included 1,019 primary valve replacements between 1989 and 1997. Seventy
      two percent of patients were men; mean (standard deviation) age was 61 (10)
      years. The preoperative New York Heart Association functional class was III or IV
      in 70% of patients. Follow-up at 9 years was 99.6% complete, comprising 2,730
      patient-years (mean, 2.7 years). RESULTS: Patient survival, including operative
      deaths, was 80% at 7 years. The linearized death rate was 2.9%/year.
      Statistically significant risk factors for mortality were diabetes, pure valve
      insufficiency, advanced age at operation, and advanced preoperative functional
      class. Linearized rates were thrombosis, 0.1%/year; thromboembolism, 1.0%/year;
      hemorrhage, 1.7%/year; endocarditis, 0.1%/year; paravalvular leak, 0.1%/year;
      reoperation, 0.1%/year; and all events, 3.0%/year. The 7-year estimates of
      freedom from complications were thrombosis, 99%; thromboembolism, 93%;
      hemorrhage, 89%; endocarditis, 99%; paravalvular leak, 99.7%; reoperation, 99%;
      and all events, 82%. No structural valve failure was observed. CONCLUSIONS: The
      low incidence of valve-related complications favors the continued use of the
      Carbomedics valve in the aortic position.

PMID- 11308157
TI  - Efficacy of pulmonary vein isolation for the elimination of chronic atrial
      fibrillation in cardiac valvular surgery.
AB  - BACKGROUND: Haissaguerre and colleagues emphasize the importance of the pulmonary
      veins as a source of ectopic foci for initiating paroxysmal atrial fibrillation
      (AF). We hypothesized that ectopic foci from the pulmonary veins could also act
      as drivers for maintaining chronic AF, and that surgical ablation of the
      pulmonary vein orifices could terminate chronic AF. METHODS: Using a computerized
      48-channel mapping system, we performed intraoperative atrial mapping in 12
      patients with chronic AF associated with mitral valve disease. Patient age ranged
      from 24 to 82 years (mean, 60.4 years). AF duration ranged from 3 to 240 months
      (mean, 92+/-84 months). Simple surgical isolation of the pulmonary vein orifices
      was performed during the mitral valve operation. RESULTS: Regular and repetitive
      activation was found in the left atria of 9 out of 12 patients, and irregular and
      chaotic activation was found in both atria of 3 out of 12 patients. Chronic AF in
      the 9 patients (75%) with regular and repetitive activation of their left atria
      was successfully treated by a simple surgical isolation of the pulmonary vein
      orifices. The other 3 patients did not recover sinus rhythm after this procedure.
      In 1 case of recurrent AF, the patient recovered sinus rhythm during the follow
      up period (AF-free rate, 83%). CONCLUSIONS: Surgical ablation of the pulmonary
      vein orifices was effective in the treatment of chronic AF associated with mitral
      valve disease. Intraoperative mapping may be useful in predicting the efficacy of
      a single pulmonary vein orifice isolation procedure.

PMID- 11308158
TI  - Successful cardiac transplantation with methanol or carbon monoxide-poisoned
      donors.
AB  - BACKGROUND: Patients succumbing to methanol or carbon monoxide poisoning are
      usually rejected for heart donation. Increasing demand for donors has lead to the
      expansion of acceptance criteria and increased use of the marginal donor.
      METHODS: We transplanted hearts from donors who had had methanol intoxication in
      three cases and carbon monoxide exposure in two cases. Standard donor evaluation
      criteria and transplantation techniques were used. RESULTS: All of the
      transplants were successful. Three of the recipients required significant
      inotropic support for a few days postoperatively; however, all of the hearts
      functioned well over the intermediate and long term. Two recipients (1 from each
      group) died of complications other than heart failure (1.5 and 2 years
      postoperatively). CONCLUSIONS: Successful heart transplantation can be achieved
      using the hearts from patients succumbing to methanol or carbon monoxide
      poisoning. Routine evaluation of cardiac function and myocardial damage is
      adequate for screening these donors. Hearts from methanol-poisoning victims may
      require longer inotropic support postoperatively before complete recovery, but
      can provide excellent long-term function and results.

PMID- 11308159
TI  - Optimal timing of revascularization: transmural versus nontransmural acute
      myocardial infarction.
AB  - BACKGROUND: Higher mortality for emergency coronary artery bypass grafting (CABG)
      after an acute myocardial infarction (AMI) is well established. Whether it
      applies to both transmural and nontransmural AMI is unclear. This information may
      have different therapeutic implications for each cohort of patients. METHODS: A
      retrospective multicenter analysis of 44,365 patients who underwent CABG after
      myocardial infarction between 1993 and 1996 by 179 surgeons at 32 hospitals in
      New York State was performed. RESULTS: Overall hospital mortality for all
      patients with or without AMI was 2.5% versus 3.1% for patients who underwent CABG
      with history of myocardial infarction. Hospital mortality decreased with
      increasing time interval between CABG and AMI; 11.8%, 9.5%, and 2.8% (p < 0.001
      for all values) for less than 6 hours, 6 hours to 1 day, and greater than 1 day,
      respectively. Patients with transmural and nontransmural AMI had identical
      mortality of 3.1%. However, different patterns emerged when comparing these two
      groups of patients with respect to time of operation. Mortality was higher in the
      transmural group if CABG was performed within 7 days after AMI. Multivariate
      analysis confirmed that CABG within 1 day and 6 hours of AMI are independent risk
      factors for mortality in the transmural and nontransmural groups, respectively.
      CONCLUSIONS: Early operation after transmural AMI has a significantly higher
      risk, and surgeons should be prepared to provide aggressive cardiac support
      including left ventricular assist devices in this ailing population. Waiting in
      some may be warranted.

PMID- 11308160
TI  - Sequential grafting of the right gastroepiploic artery in coronary artery bypass
      surgery.
AB  - BACKGROUND: Only a few studies have been done on sequential grafting using the
      right gastroepiploic artery (GEA). METHODS: Forty patients (35 males, ages 36 to
      74 years) who underwent sequential grafting of the GEA were reviewed. Angiography
      of the GEA was performed preoperatively in all patients. GEAs with a luminal
      diameter greater than 2 mm at the presumptive distal anastomosis on the angiogram
      were used. The dissected GEA was led into the pericardial cavity through the
      antegastric route. We used GEAs to graft 89 branches (2.2 per patient) in the
      inferoposterior region. RESULTS: In 24 patients who had angiographic
      examinations, all the GEAs were patent, although luminal narrowing was noted in
      the segment between the two anastomoses in 3 patients. Eight-year actuarial
      survival was 92.5% and the cardiac-related event-free rate was 95%. CONCLUSIONS:
      Sequential grafting of the GEA can be performed effectively in selected patients.
      Performing preoperative angiography to assess the size of the GEA for sequential
      grafting is strongly recommended.

PMID- 11308161
TI  - Limited flow capacity of the right gastroepiploic artery graft: postoperative
      echocardiographic and angiographic evaluation.
AB  - BACKGROUND: The flow capacity of the right gastroepiploic artery graft has not
      been clarified. METHODS: Angiographic and echocardiographic studies were
      conducted in 30 patients who had undergone coronary artery bypass grafting using
      both the internal thoracic and right gastroepiploic arteries. The luminal
      diameter of the arterial grafts was measured from the postoperative angiograms.
      The adequacy of the myocardial blood supply from the arterial grafts was
      evaluated by dobutamine stress echocardiography. RESULTS: With echocardiography,
      14 patients exhibited an ischemic response in the gastroepiploic artery grafted
      region, whereas no patients exhibited an ischemic response in the internal
      thoracic artery grafted area. The luminal diameter of the gastroepiploic artery
      and a younger age were correlated with the ischemic response observed in the
      dobutamine stress echocardiography. A luminal diameter of the gastroepiploic
      artery of greater than 2.6 mm had the highest sensitivity and specificity for a
      nonischemic change. CONCLUSIONS: To generate the maximal flow reserve, the
      luminal diameter of the gastroepiploic artery when used as a graft should be
      sufficiently large enough, nearly 3 mm at the anastomosis.

PMID- 11308162
TI  - Off-pump coronary operations can be safely taught to cardiothoracic trainees.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) operations are evolving
      rapidly and becoming established in many cardiothoracic centers. For the
      technique to be widely applicable, teaching methods must be developed for
      surgical trainees. Early and midterm clinical outcomes of OPCAB performed at our
      institution by trainees as first operators under supervision were compared to
      those obtained in patients operated on by consultants. METHODS: Analysis was
      undertaken on data prospectively inserted in the Patient Analysis & Tracking
      System. Of the 559 OPCAB operations performed between January 1997 and May 2000,
      124 (22%) were carried out by a supervised trainee and 435 (78%) by a consultant.
      RESULTS: There was no difference in age, sex, angina class, New York Heart
      Association functional class, or operative priority and extent of coronary artery
      disease in the two groups. More patients operated on by consultants had a history
      of congestive heart failure requiring medical therapy, significantly lower
      ejection fraction, and higher Parsonnet score compared with patients operated on
      by trainees. Early and midterm clinical results, in terms of morbidity and
      mortality, were similar in patients operated on by trainees or by consultants.
      CONCLUSIONS: Our data show no differences in early and midterm clinical outcome
      for patients undergoing OPCAB operations performed either by consultants or by
      trainees under supervision. The improvements in exposure and stabilization
      techniques, as well as the use of intracoronary shunts, have made it possible and
      safe to teach trainees off-pump multivessel coronary artery revascularization.

PMID- 11308163
TI  - Elective intraaortic balloon counterpulsation for high-risk off-pump coronary
      artery bypass operations.
AB  - BACKGROUND: Dislocations of the heart required for exposure and construction of
      distal anastomoses often produce hemodynamic instability when performing coronary
      artery revascularization without using cardiopulmonary perfusion (OPCAB). We
      report our early experience with elective intraaortic balloon counterpulsation
      (IABP) to enable and facilitate selected high-risk patients to undergo OPCAB.
      METHODS: Sixteen high-risk patients undergoing multivessel OPCAB using elective
      IABP are reported. The patients were believed to be at increased risk because of
      the presence of severe proximal multivessel coronary artery obstruction,
      ventricular dysfunction, recent acute myocardial infarction, cardiomegaly
      cardiomyopathy, and documented cerebral vascular disease. The presence of
      significant comorbid disease also made the avoidance of cardiopulmonary bypass
      desirable, if at all possible, in all patients. RESULTS: The IABP appeared to
      facilitate the intraoperative management of our series of patients. This was
      evidenced by improved hemodynamic stability and virtual elimination of the need
      for inotropic support during the dislocations of the heart needed for exposure
      and construction of distal anastomoses. There were no complications related to
      use of IABP. There was one death. CONCLUSIONS: We believe this strategy to use
      IABP selectively can allow surgeons to safely extend the benefits of OPCAB
      procedures to high-risk patients and avoid dangerous hemodynamic instability that
      otherwise, often occurs.

PMID- 11308164
TI  - Early results of coronary grafting using ultrasonically skeletonized internal
      thoracic arteries.
AB  - BACKGROUND: We have developed an ultrasonic complete skeletonization technique
      for obtaining internal thoracic artery (ITA) grafts and have used this method
      clinically since January 1998. In this report, we discuss the early results of
      bilateral ITA grafts obtained with our method. METHODS: We studied 200
      consecutive patients who underwent coronary artery bypass grafting using ITAs
      obtained by this technique. Angiography of the grafts was performed in 188
      patients (94%) within 1 month after coronary artery bypass grafting. RESULTS: The
      ITA grafts were about 4 cm longer than pedicled ITA grafts. The free flow through
      the grafts was at least 30% higher than through pedicled ITAs. The early patency
      rate determined by postoperative angiography of the grafts was 99.7% for left
      ITAs and 100% for right ITAs. No patient required postoperative intervention or
      repeated surgery. CONCLUSIONS: Ultrasonic complete skeletonization increases the
      effective length of ITA bypasses, improves free flow through the bypasses, and it
      is less invasive than conventional pedicled harvesting. These excellent early
      results indicate that this technique is a straightforward, safe, less invasive,
      and optimal method for obtaining ITA bypass grafts.

PMID- 11308165
TI  - Contrast-enhanced magnetic resonance angiography of mammary artery grafts after
      minimally invasive coronary bypass surgery.
AB  - BACKGROUND: The aim of the study was to investigate the application of the
      contrast-enhanced magnetic resonance angiography (CE-MRA) for the visualization
      of left internal mammary artery (LIMA) bypass. METHODS: A total of 30 patients
      with LIMA bypass (22 men, 8 women, 35 to 77 years) received a CE-MRA 4 to 20 days
      after surgery. The non-ECG-triggered CE-MRA was performed during expiration using
      a body array coil at a 1.5 Tesla scanner (Magnetom-Vision). A three-dimensional
      gradient-echo sequence with slice interpolation technique was applied. For the
      three-dimensional visualization, single coronal slices were postprocessed with
      maximal intensity projection. Of 30 patients 22 agreed to a comparative coronary
      angiography. RESULTS: Five bypasses were identified up to the end-to-side
      anastomosis. A total of 80% of the bypass course was detectable in 13 patients
      and 60% in 11 patients. In two LIMA bypasses only 30% of the proximal part could
      be viewed; one was found by conventional coronary angiography to be occluded. The
      other conventional coronary angiography showed the LIMA bypass to be patent.
      CONCLUSIONS: The complete course of the LIMA bypass to the left anterior
      descending coronary artery can be visualized by the MRA technique. The most
      reliable imaging of the distal anastomosis can be realized by reducing the
      negative influence of the beating heart.

PMID- 11308166
TI  - A new predictive model for adverse outcomes after elective thoracoabdominal
      aortic aneurysm repair.
AB  - BACKGROUND: Recent recommendations have emphasized individualized treatment based
      on balancing a patient's risk of thoracoabdominal aortic aneurysm rupture with
      the risk of an adverse outcome after surgical repair. The purpose of this study
      was to determine which preoperative risk factors currently predict an adverse
      outcome after elective thoracoabdominal aortic aneurysm repair. METHODS: A
      single, composite end point termed adverse outcome was defined as the occurrence
      of any of the following: death within 30 days, death before discharge from the
      hospital, paraplegia, paraparesis, stroke, or acute renal failure requiring
      dialysis. A risk factor analysis was performed using data from 1,108 consecutive
      elective thoracoabdominal aortic aneurysm repairs. RESULTS: The incidence of an
      adverse outcome was 13.0% (144 of 1,108 patients); predictors included
      preoperative renal insufficiency (p = 0.0001), increasing age (p = 0.0035),
      symptomatic aneurysms (p = 0.020), and extent II aneurysms (p = 0.0001). These
      risk factors were used to construct an equation that estimates the probability of
      an adverse outcome for an individual patient. CONCLUSIONS: This new predictive
      model may assist in decisions regarding elective thoracoabdominal aortic aneurysm
      operations. For patients who are acceptable candidates, contemporary surgical
      management provides favorable results.

PMID- 11308167
TI  - Preoperative risk factors for hospital mortality in acute type A aortic
      dissection.
AB  - BACKGROUND: Acute type A dissection is associated with postoperative
      complications and a high mortality rate. This study was performed to determine
      the perioperative risk factors leading to hospital mortality in patients with
      acute type A aortic dissection. METHODS: One hundred twenty-two patients with
      acute type A aortic dissection treated surgically within 48 hours after onset
      were enrolled in this study. Thirty-two perioperative risk factors were used in
      statistical analysis for prediction of mortality. Risk factors for hospital death
      were investigated with univariate and multiple logistic regression analysis.
      RESULTS: The in-hospital mortality rate including operative death was 12.3% (15
      of 122 patients) and the actuarial survival rate (including in-hospital death)
      was 72%+/-6% at 5 years. Univariate analysis revealed 10 risk factors to be
      statistically significant predictors of hospital death: age, year of operation
      (1990 to 1995), Marfan syndrome, preoperative ST segment elevation, heart failure
      from aortic regurgitation, preoperative shock, preoperative coma, long operation
      time (> 6 hours), long cardiopulmonary bypass time (> 4 hours), and massive blood
      transfusion (> 20 units) (p < 0.05). Multiple logistic regression analysis
      confirmed preoperative ST-T segment elevation and massive blood transfusion to be
      statistically significant independent risk factors for hospital death (p < 0.05).
      CONCLUSIONS: Preoperative ST-T elevation and massive blood transfusion during
      operation were identified as significant independent risk factors for hospital
      mortality after operation for acute type A aortic dissection. Our findings should
      contribute to estimation of operative risk in individual patients.

PMID- 11308168
TI  - Does the extent of proximal or distal resection influence outcome for type A
      dissections?
AB  - BACKGROUND: The extent of proximal and distal aortic resection that should be
      performed for acute type A aortic dissections remains controversial. METHODS:
      From 1984 to 1999, 119 patients underwent repair of an acute type A dissection.
      Distal resection was to the ascending aorta in 78 (66%) and hemiarch in 41 (34%)
      patients. Proximally, the aortic valve was preserved in 69 (58%) patients, 40
      (34%) underwent composite valve grafting, and 10 (8%) underwent separate graft
      and valve replacement. RESULTS: Operative mortality was higher for separate graft
      and valve (50%+/-16%) than for valve preservation (16%+/-5%) or composite grafts
      (20%+/-7%) (p < 0.05). Hemiarch replacement did not increase operative risk
      compared to distal reconstruction to the ascending aorta (17%+/-6% versus 22%+/
      5%, p > 0.71). At 10 years, freedom from reoperation was 81%+/-7% and long-term
      survival was 60%+/-8%, but neither was related to the proximal or distal surgical
      technique (p > 0.15). Risk factors for late reoperation included a nonresected
      primary tear and Marfan syndrome (p < 0.05). CONCLUSIONS: An aggressive surgical
      approach, including a full root or hemiarch replacement, is not associated with
      increased operative risk and should be considered when type A dissections
      extensively involve the valve, sinuses, or arch.

PMID- 11308169
TI  - Bulboventricular foramen resection: hemodynamic and electrophysiologic results.
AB  - BACKGROUND: The two major surgical approaches to the relief of bulboventricular
      foramen (BVF) obstruction in patients with single left ventricle (LV) are the
      Damus-Kaye-Stansel (DKS) procedure or direct BVF resection. Theoretical
      advantages of the DKS include better out-flow gradient relief, lower potential
      incidences of postoperative heart block and lower incidences of reoperation.
      Potential disadvantages of this approach include increased semilunar valvar
      insufficiency, lack of feasibility when attempting septation-type operations for
      univentricular hearts, and a technically more difficult operation. We report the
      results of direct surgical BVF resection. METHODS: From June 1990 to June 1999, 9
      patients had direct BVF resection performed at our institution. The median age at
      surgery was 16.5 years (range 1 month to 27 years). Diagnoses in these patients
      were [S,L,L] single LV (n = 8) and [S,D,D] single LV tricuspid atresia (n = 1).
      Eight of 9 patients had pulmonary artery bands placed either before BVF resection
      or at the same time as this procedure. Three patients required reoperation for
      reobstruction at the BVF (12 total operations in 9 patients). RESULTS: Median
      preoperative peak systolic gradient across the BVF measured at cardiac
      catheterization was 47 mm Hg (range 10 to 63 mm Hg). The median peak gradient
      measured by Doppler echocardiography was 44 mm Hg (range 5 to 125 mm Hg). Eight
      of 9 patients survived the operation to discharge from the hospital and 7 of 9
      are alive at follow-up. At a median follow-up of 22 months (range 5 to 76
      months), 8 of 8 surviving patients had an unobstructed BVF as determined by
      qualitative two-dimensional echocardiography and Doppler color flow imaging.
      There was one perioperative and one late death 5 months postoperatively
      (secondary to fungal sepsis). No patient developed new or worsened aortic
      insufficiency after BVF resection. Eight of 9 patients had no change in AV nodal
      conduction after surgery. One patient developed Mobitz II heart block requiring
      postoperative implantation of a pacemaker. CONCLUSIONS: Direct resection of an
      obstructive BVF can be performed with total relief of obstruction although
      reoperation may be required. Atrioventricular nodal function can be preserved in
      most patients with this operative approach, including those with [S,L,L]
      segmental anatomy.

PMID- 11308170
TI  - Systemic right ventricular failure after atrial switch operation: midterm results
      of conversion into an arterial switch.
AB  - BACKGROUND: Failure of the systemic right ventricle after atrial switch operation
      can be treated by conversion into an arterial switch operation. METHODS: Four
      patients, age 38 to 59 months, presented with right ventricular failure after
      Senning operation and ventricular septal defect closure. One patient had elevated
      left ventricular pressure; in the other three patients the left ventricle was
      retrained to a left ventricular/right ventricular pressure ratio of 0.8 or
      greater by pulmonary artery banding in 12 to 24 months. RESULTS: Postoperative
      course after arterial switch operation was prolonged, but clinical condition was
      good at discharge. Fractional shortening ranged from 20% to 28%. Trace-to
      moderate aortic regurgitation was present; only 1 patient had preserved sinus
      rhythm. After a mean follow-up of 43.5 months 1 patient had died due to left
      ventricular dysfunction. The survivors are in New York Heart Association
      functional class I to II. Fractional shortening has improved (29% to 37%); aortic
      regurgitation has not increased. No patient has undisturbed sinus rhythm.
      CONCLUSIONS: Conversion of an atrial into an arterial switch is an alternative to
      cardiac transplantation in childhood. However, the procedure is demanding. Long
      term morbidity is caused by rhythm disturbances. Aortic valve performance and
      left ventricular function require close observation.

PMID- 11308171
TI  - Surgery for coarctation of the aorta in infants weighing less than 2 kg.
AB  - BACKGROUND: Low- and very low-birth weight infants are now candidates for
      reparative cardiac surgery. Outcomes after coarctation repair have not been
      characterized in this patient population. METHODS: We performed a retrospective
      review of 18 consecutive neonates less than 2 kg who underwent repair of aortic
      coarctation between August 1990 and December 1999. RESULTS: Median weight was
      1,330 g, and median gestational age was 31 weeks. A ventricular septal defect was
      present in 5 patients, and Shone's complex in 4. Sixteen patients had resection
      and end-to-end anastomosis, and 2 had resection and subclavian flap. Median clamp
      time was 15.5 minutes. One patient died during hospitalization. Two patients died
      late postoperatively (5-year estimated survival 80%). Mean follow-up was 28.5
      months. Eight patients (44%) had a residual or recurrent coarctation, 5 underwent
      balloon dilation, and 3 underwent reoperation. Freedom from reintervention for
      recoarctation was 60% at 5 years. Shone's complex or a hypoplastic arch was an
      independent risk factor for decreased survival (p < 0.001). Very low birth weight
      was a multivariate predictor for increased risk of recoarctation (p = 0.01).
      CONCLUSIONS: Coarctation repair in less than 2-kg premature non-Shone's infants
      can be performed with a low mortality. The rate of recoarctation is higher in the
      very low-birth weight infants, but can be managed with low risk.

PMID- 11308172
TI  - Division of modified Blalock-Taussig shunt at correction avoids distortion of the
      pulmonary artery.
AB  - BACKGROUND: Modified Blalock-Taussig (BT) shunt causing pulmonary artery
      distortion has been reported. This distortion may get worse after a corrective
      operation if the BT shunt is ligated, rather than divided. In this study we
      examined whether division of modified BT shunt at the time of corrective
      operation would allow pulmonary artery growth and avoid further distortion.
      METHODS: Fifteen patients who had modified BT shunts and subsequently had
      corrective operations performed by one surgeon between January 1980 to December
      1990 were analyzed. The median time from the BT shunt to corrective operation was
      46.3 months (range, 3 to 119 months). At the time of corrective procedure, the BT
      shunt was divided and metal clips were used to occlude and mark each end. At
      follow-up a chest roentgenogram was obtained and the distance between the two
      clips was measured. RESULTS: In all 15 patients measured sequentially the
      distances between the two clips increased steadily. CONCLUSIONS: Division of BT
      shunt at the time of corrective procedure reduces pulmonary artery distortion.

PMID- 11308173
TI  - Assisted venous drainage cardiopulmonary bypass in congenital heart surgery.
AB  - BACKGROUND: A novel active venous drainage perfusion circuit was designed to
      achieve effective venous return through small venous cannulas. The efficacy and
      safety of this new system was investigated and compared with a conventional
      gravity drainage system. METHODS: Four hundred consecutive patients undergoing
      open heart repair of congenital heart lesions by one surgeon were studied. The
      first 200 patients were supported by gravity drainage and the next 200 patients
      were supported by assisted venous drainage. No patient in the time period was
      excluded from the study. RESULTS: The two groups did not differ significantly in
      weight, bypass time, or cross-clamp time. Priming volumes were less in the
      assisted group than in the gravity group (576+/-232 mL versus 693+/-221 mL, p <
      0.001). Venous cannula size was smaller in the assisted group when compared with
      the gravity group (33.2F+/-7.4F versus 38.5F+/-7.1F, p < 0.001). There was a
      trend to lower operative mortality in the assisted drainage group (5 of 200, 2.5%
      versus 11 of 200, 5.5%; p = 0.10). Hospital stay and pulmonary, infectious, and
      neurologic complications were comparable in both groups. Cardiac complications
      were less common in the assisted group than in gravity group (22 of 200, 11%
      versus 38 of 200, 19%; p = 0.017). Hematologic complications were less common in
      the assisted group than the gravity group (6 of 200, 3% versus 19 of 200, 9.5%; p
      < 0.01). CONCLUSIONS: These findings suggest that assisted venous drainage is
      safe in congenital heart operations and facilitates the use of smaller venous
      cannulas.

PMID- 11308175
TI  - Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic
      protection.
AB  - BACKGROUND: Mitochondrial and sarcolemmal ATP-sensitive potassium channels have
      been implicated in cardioprotection; however, the role of these channels in
      magnesium-supplemented potassium (K/Mg) cardioplegia during ischemia or
      reperfusion is unknown. METHODS: Rabbit hearts (n = 76) were used for Langendorff
      perfusion. Sham hearts were perfused for 180 minutes. Global ischemia hearts
      received 30 minutes of global ischemia and 120 minutes of reperfusion. K/Mg
      hearts received cardioplegia before ischemia. The role of ATP-sensitive potassium
      channels in K/Mg cardioprotection during ischemia and reperfusion was
      investigated, separately using the selective mitochondrial ATP sensitive
      potassium and channel blocker, 5-hydroxydecanoate, and the selective sarcolemmal
      ATP-sensitive potassium channel blocker HMR1883. Separate studies were performed
      using the selective mitochondrial ATP-sensitive potassium channel opener,
      diazoxide, and the nonselective ATP-sensitive potassium channel opener pinacidil.
      RESULTS: Infarct size was 1.9%+/-0.4% in sham, 3.7%+/-0.5% in K/Mg, and 27.8%+/
      2.4% in global ischemia hearts (p < 0.05 versus K/Mg). Left ventricular peak
      developed pressure (percent of equilibrium) at the end of 120 minutes of
      reperfusion was 91%+/-6% in sham, 92% +/-2% in K/Mg, and 47%+/-6% in global
      ischemia (p < 0.05 versus K/Mg). Blockade of sarcolemmal ATP-sensitive potassium
      channels in K/Mg hearts had no effect on infarct size or left ventricular peak
      developed pressure. However, blockade of mitochondrial ATP-sensitive potassium
      channels before ischemia significantly increased infarct size to 23%+/-2% in K/Mg
      hearts (p < 0.05 versus K/Mg; no statistical significance [NS] as compared to
      global ischemia) and significantly decreased left ventricular peak-developed
      pressure to 69%+/-4% (p < 0.05 versus K/Mg). Diazoxide when added to K/Mg
      cardioplegia significantly decreased infarct size to 1.5%+/-0.4% (p < 0.05 versus
      K/Mg). CONCLUSIONS: The cardioprotection afforded by K/Mg cardioplegia is
      modulated by mitochondrial ATP-sensitive potassium channels. Diazoxide when added
      to K/Mg cardioplegia significantly reduces infarct size, suggesting that the
      opening of mitochondrial ATP-sensitive potassium channels with K/Mg cardioplegic
      protection would allow for enhanced myocardial protection in cardiac operations.

PMID- 11308174
TI  - A novel organ culture method to study intimal hyperplasia at the site of a
      coronary artery bypass anastomosis.
AB  - BACKGROUND: Intimal hyperplasia or restenosis at the site of a coronary artery
      bypass anastomosis contributes to early graft failure, and growth factor release
      in response to construction of the anastomotic site strongly influences this
      process. Due to the difficulties in studying restenosis after coronary artery
      bypass graft surgery, we have tested whether an organ culture model we have
      developed can simulate the early events associated with intimal hyperplasia.
      METHODS: End-to-side anastomosis of porcine radial artery to porcine coronary
      artery were constructed. The vessels were trimmed and incubated under standard
      tissue culture conditions for 14 days. Appropriate controls were treated
      similarly. The vessels were frozen, cryosectioned, and immunostained for the
      expression of the proliferation marker proliferating cell nuclear antigen (PCNA).
      A proliferative index (PCNA positive nuclei/total nuclei) was calculated for
      comparative purposes. RESULTS: Limited PCNA staining was observed in noncultured
      vessel segments (0.046+/-0.045). A slight increase in this index was observed in
      vessels that had been placed into culture without manipulation (0.230+/-0.141)
      and in vessels subjected to an arteriotomy (0.462+/-0.249). However, the most
      significant increase was obtained after construction of an anastomosis (4.98+/
      6.66). No change in total cell number was evident over the course of the
      experiment or in relation to the treatment. CONCLUSIONS: Culture conditions and
      incision slightly stimulate cell proliferation in porcine coronary artery
      segments when compared with basal conditions of a native artery. In contrast,
      construction of an anastomosis increases proliferation 108-fold. Therefore,
      surgical manipulation of arterial conduits during construction of an anastomotic
      site is the primary trigger for intimal hyperplasia, independent of dissection
      and incision of the vessel. Furthermore, these data indicate the organ culture
      model we have developed will be useful for examining the cellular and molecular
      mechanisms that mediate intimal hyperplasia at the site of a coronary artery
      bypass graft anastomosis.

PMID- 11308176
TI  - Cell volume and ionic transport systems after cold preservation of coronary
      endothelial cells.
AB  - BACKGROUND: Hypothermia-induced changes in cell volume and ionic transport
      systems of coronary endothelial cells may play a role in the development of
      coronary artery disease in cardiac transplant recipients. METHODS: Coronary
      endothelial cells were incubated in University of Wisconsin solution or culture
      control medium for up to 48 hours at 4 degrees C. Parallel control cultures were
      incubated at 37 degrees C. Na/K-ATPase and Na/K/Cl cotransport activities were
      determined as ouabain- and furosemide-sensitive 86Rb+ uptake, respectively. Cell
      volume changes and cell death were analyzed by a FACScan flow cytometer and the
      release of lactate dehydrogenase, respectively. RESULTS: Coronary endothelial
      cells stored in University of Wisconsin solution up to 6 hours showed an
      increased Na/K-ATPase activity compared to control cells, whereas no changes were
      observed in Na/K/Cl cotransport activity or cell volume. Long-term preservation
      (24 and 48 hours) was associated with a partial loss of cell viability, as
      demonstrated by lactate dehydrogenase release, and dramatic alterations in ionic
      transport system activities. CONCLUSIONS: University of Wisconsin solution seems
      to prevent coronary endothelial cells Na/K/Cl cotransport activity changes during
      cold preservation, which could alter cell volume regulation and cause cell
      injury.

PMID- 11308177
TI  - Preconditioning protects the severely atherosclerotic mouse heart.
AB  - BACKGROUND: Coronary atherosclerosis has profound effects on vascular and
      myocardial biology, and it has been speculated that the atherosclerotic heart
      does not benefit from ischemic preconditioning. METHODS: To investigate if
      atherosclerosis would influence the preconditioning response, Apolipoprotein
      E/low density lipoprotein (LDL) receptor double knockout mice (ApoE/LDLr-/-) were
      fed an atherogenic diet (21% fat, 0.15% cholesterol) for 6 to 8 months. At that
      time, extensive atherosclerotic lesions throughout the coronary tree were seen in
      transverse sections stained with Oil Red-O. Hearts of ApoE/LDLr-/- mice were
      Langendorff-perfused with 40 minutes of global ischemia and 60 minutes
      reperfusion, and compared with C57BL/6 controls. Preconditioning with two
      episodes of 2 minutes of ischemia and 5 minutes reperfusion, or exposing the mice
      to a hyperoxic environment (O2 > 98%) for 60 minutes before heart perfusion, was
      performed. RESULTS: Hearts of mice with coronary atherosclerosis had worse
      postischemic function, and increased infarct size and troponin T release compared
      to hearts of C57BL/6 mice. Ischemic preconditioning improved postischemic
      ventricular function, and reduced myocardial infarct size and troponin T release
      in both normal and ApoE/LDLr-/- mice. The effects were most pronounced in
      ApoE/LDLr-/- hearts. Exposure to hyperoxia exerted a similar protection of
      function and cell viability of ApoE/LDLr-/- mice hearts. CONCLUSIONS: These
      findings suggest that the severely atherosclerotic heart may be protected by
      preconditioning induced by ischemia or hyperoxia.

PMID- 11308178
TI  - Pentoxifylline reduces coronary leukocyte accumulation early in reperfusion after
      cold ischemia.
AB  - BACKGROUND: Ischemia/reperfusion injury can complicate recovery in cardiac
      operations. Ischemia induces endothelial dysfunction, which may contribute to
      leukocyte accumulation during reperfusion. Leukocyte-mediated injury may then
      occur. Using intravital microscopy we previously reported increased leukocyte
      retention in coronary capillaries and venules during early reperfusion during
      warm ischemia/reperfusion. In this study we investigated whether cold
      cardioplegic protection would limit leukocyte sequestration in coronary
      microvessels early in reperfusion. Pentoxifylline (PTX) has antiinflammatory
      effects and may limit endothelial dysfunction during ischemia/reperfusion. The
      effect of cardioplegia modification with PTX was also examined. METHODS: Isolated
      rat hearts were subjected to 90 minutes of 4 degrees C ischemia after arrest with
      cardioplegia. Hearts were reperfused with diluted whole blood containing
      fluorescent-labeled leukocytes. Leukocyte retention in coronary microvessels was
      observed with intravital microscopy. Three groups were studied, nonischemic
      control, cold ischemia, and PTX-modified cold ischemia. RESULTS: In coronary
      capillaries, leukocyte trapping was nearly doubled in unmodified cold ischemia
      versus control. PTX modification significantly reduced leukocyte accumulation. In
      coronary venules, greater leukocyte adhesion was observed in unmodified cold
      ischemia compared to nonischemic controls. PTX modification significantly reduced
      leukocyte adhesion. CONCLUSIONS: Cold cardioplegia did not prevent leukocyte
      retention in the coronary microcirculation early in reperfusion. PTX modification
      of cardioplegia significantly reduced leukocyte sequestration in coronary
      capillaries and venules. Preserving endothelial function during ischemia may
      limit leukocyte accumulation and ischemia/reperfusion injury after cardiac
      operation.

PMID- 11308179
TI  - Laboratory confirmation of clinical heart allograft preservation variability.
AB  - BACKGROUND: Previously, we reported survival differences from the national heart
      transplant registry favoring centers that used intracellular organ preservation
      solutions. To eliminate center selection bias, we tested some of these solutions
      in a biventricular working rat heart model to determine their relative efficacy.
      METHODS: Using 103 Sprague-Dawley rat hearts perfused with modified Krebs
      Henseleit buffer, both ventricles functioned with adjustable independent preload
      and afterload and their pressure-length loops generated load-insensitive
      measurements of cardiac performance. After 15 minutes of stable function, each
      heart sustained 180 minutes of cold (4 degrees C) ischemia after a 5-minute
      perfusion by University of Missouri (UMC), Plegisol, Collins, University of
      Wisconsin, Custodiol, or Roe solutions. Eighty-two hearts were reperfused and the
      remainder were used for ATP analyses. RESULTS: Although the extracellular
      solution Plegisol showed good recovery of traditional hemodynamic values,
      including developed pressure and cardiac output, intracellular solutions like Roe
      had superior preservation of load-insensitive indices such as preload recruitable
      stroke work: Roe (intracellular) 103%+/-13%; Custodiol (intracellular) 96%+/-9%;
      UW (intracellular) 69%+/-12%; Collins (intracellular) 68%+/-9%; Plegisol
      (extracellular) 68%+/-7%; and University of Missouri (extracellular) 56%+/-10% (p
      = 0.04). Furthermore, recovery with intracellular solutions tended to be gradual
      but more progressive after ischemia in contrast to an early plateau shown by
      extracellular (p < 0.001). Right ventricular recovery and ATP measurements were
      similar between groups. CONCLUSIONS: These data support the superiority of
      certain intracellular preservation solutions and provide evidence that optimal
      heart organ protection may be difficult to judge clinically using hemodynamic
      values routinely available to the heart transplant surgeon. Care should be taken
      to verify the performance of some solutions used in heart organ transplantation.

PMID- 11308180
TI  - Myocardial function in hearts with transgenic overexpression of the G protein
      coupled receptor kinase 5.
AB  - BACKGROUND: Chronic heart failure is associated with impairment of the myocardial
      beta-adrenergic receptor (beta-AR) system. In this study, the effects of G
      protein-coupled receptor kinase 5 (GRK5) overexpression on myocardial performance
      were directly assessed in the hearts of transgenic mice using an isolated work
      performing murine heart preparation and computerized analysis of functional data.
      METHODS: A controlled experimental study was performed to evaluate cardiac
      function in both transgenic mice with a 30-fold overexpression of GRK5 (n = 9, 23
      to 29 g) and littermate controls (n = 10, 22 to 29 g). Preload-dependent cardiac
      output, contractility, stroke work, stroke volume, and heart rate were compared
      between the two groups. RESULTS: Significant decreases in preload-dependent
      cardiac output and contractility were observed in the mice with GRK5
      overexpression when compared with control group mice and occurred in association
      with significant decreases in stroke work and stroke volume. There was no
      significant difference in the average heart rate between the two groups.
      CONCLUSIONS: These data suggest that GRK5 upregulation may be partially
      responsible for alterations in myocardial function in chronic heart failure.

PMID- 11308181
TI  - Histopathologic consequences of hyperglycemic cerebral ischemia during
      hypothermic cardiopulmonary bypass in pigs.
AB  - BACKGROUND: This study examined whether 34 degrees C or 31 degrees C hypothermia
      during global cerebral ischemia with hyperglycemic cardiopulmonary bypass (CPB)
      in surviving pigs improves electroencephalographic (EEG) recovery and
      histopathologic scores when compared with normothermic animals. METHODS:
      Anesthetized pigs were placed on CPB and randomly assigned to 37 degrees C (n =
      9), 34 degrees C (n = 10), or 31 degrees C (n = 8) management. After increasing
      serum glucose to 300 mg/dL, animals underwent 15 minutes of global cerebral
      ischemia by temporarily occluding the innominate and left subclavian arteries.
      Following reperfusion, rewarming, and termination of CPB, animals were recovered
      for 24 (37 degrees C animals) or 72 hours (34 degrees C and 31 degrees C
      animals). Daily EEG signals were recorded, and brain histopathology from
      cortical, hippocampal, and cerebellar regions was graded by an independent
      observer. RESULTS: Before ischemia, serum glucose concentrations were similar in
      the 37 degrees C (307+/-9 mg/dL), 34 degrees C (311+/-14 mg/dL), and 31 degrees C
      (310+/-15) groups. By the first postoperative day, EEG scores in 31 degrees C
      animals (4.2+/-0.6) had returned to baseline and were greater than those in the
      34 degrees C (3.4+/-0.5) and 37 degrees C (2.5+/-0.4) groups (p < 0.05,
      respectively, between groups). Cooling to 34 degrees C showed selective
      improvement over 37 degrees C in hippocampal, temporal cortical, and cerebellar
      regions, but the greatest improvement in all regions occurred with 31 degrees C.
      Cumulative neuropathology scores in 31 degrees C animals (13.5+/-2.2) exceeded 34
      degrees C (6.8+/-2.2) and 37 degrees C (1.9+/-2.1) animals (p < 0.05,
      respectively, between groups). CONCLUSIONS: Hypothermia during CPB significantly
      reduced the morphologic consequences of severe, temporary cerebral ischemia under
      hyperglycemic conditions, with the greatest protection at 31 degrees C.

PMID- 11308182
TI  - Treatment of severe carinal stenosis with overlapping metallic endoprosthesis.
AB  - A 50-year-old man presented with respiratory distress from central airway
      compression secondary to malignant mediastinal adenopathy. The stenosis involved
      the carinal triangle and created residual luminal diameters of 6 mm, 6 mm, and
      pinhole in the distal trachea and right and left mainstem bronchi, respectively.
      Airway patency at the carina was restored successfully with a stenting method
      that uses two overlapping Wall stents.

PMID- 11308183
TI  - Solitary pulmonary lymphangioma.
AB  - Lymphangioma is an abnormal collection of lymphatics that are developmentally
      isolated from the normal lymphatic system. Lymphangioma rarely presents as a
      solitary pulmonary lesion. We present a case of solitary pulmonary lymphangioma
      and review the literature on its pathogenesis, clinical features, and
      radiographic findings.

PMID- 11308184
TI  - Dysphagia caused by a fetus-in-fetu in a 27-year-old man.
AB  - Mechanical obstruction of the distal esophagus by a fetus-in-fetu is an extremely
      rare condition that has not been previously reported. We present the case of a 27
      year-old man who presented with dysphagia caused by fetus-in-fetu contained
      within a retroperitoneal cystic cavity. The tumor, noticed since childhood, did
      not cause any symptoms until a year before presentation when symptoms of
      dysphagia developed. We propose including this entity in the differential
      diagnosis of a retroperitoneal mass.

PMID- 11308185
TI  - Subcutaneous emphysema of the thorax heralding colonic perforation.
AB  - Subcutaneous emphysema of the thorax may follow thoracic operations for a number
      of essentially benign reasons and does not usually cause much concern to the
      thoracic surgeon. We report subcutaneous emphysema of the thorax heralding a
      retroperitoneal colonic perforation in a patient who had undergone coronary
      artery bypass grafting 3 days previously.

PMID- 11308186
TI  - Combined off-pump coronary surgery and right lung resections through midline
      sternotomy.
AB  - Concomitant severe coronary artery disease and lung malignancies are uncommon.
      Combining conventional coronary surgery with cardiopulmonary bypass with lung
      resection is still a controversial issue. Conversely, combining off-pump coronary
      surgery with right lung resections through a midline sternotomy can be an
      attractive approach. Off-pump coronary surgery avoids the risks of
      cardiopulmonary bypass, reduces systemic inflammatory response and does not
      affect the immune system. We report a series of three patients successfully
      operated using this approach.

PMID- 11308187
TI  - Midterm results after ventricular septation for double-inlet left ventricle in
      early infancy.
AB  - We performed ventricular septation for a 40-day-old boy with double-inlet left
      ventricle and discordant ventriculoarterial connection but without pulmonary
      stenosis. Postoperative cardiac function is satisfactory, with no evidence of
      pulmonary hypertension or subaortic stenosis. Nine years after the operation, the
      patient has an active life, is free from symptoms, and requires no medication. He
      may be the first patient to survive ventricular septation for double-inlet left
      ventricle in early infancy.

PMID- 11308188
TI  - Aneurysmal pericardial patch producing right ventricular inflow obstruction.
AB  - A 2-month-old infant presented with acute onset of heart failure, having
      previously undergone anatomical repair of transposition of the great arteries and
      ventricular septal defect (VSD). Echocardiography demonstrated aneurysmal
      dilation of the native pericardial patch used for VSD closure, resulting in right
      ventricular inflow obstruction. The pericardial patch was excised, and the VSD
      closed using a GoreTex patch.

PMID- 11308189
TI  - Pulmonary root translocation for biventricular repair of double-outlet left
      ventricle.
AB  - Double-outlet left ventricle is conventionally repaired with an extracardiac
      conduit when pulmonary stenosis is present. We report the use of pulmonary root
      translocation to the right ventricle to construct the posterior wall with
      autologous tissue and a porcine pericardial monocusp ventricular outflow patch
      anteriorly for 2 patients with double-outlet left ventricle. This technique
      allows minimization of pulmonary insufficiency, avoids coronary artery ligation
      with infundibulotomy, and has a major theoretical advantage for growth potential.

PMID- 11308190
TI  - Cleft on tricuspid anterior leaflet.
AB  - We report a case of isolated congenital tricuspid regurgitation caused by a cleft
      in the anterior tricuspid leaflet associated with a patent foramen ovale.
      Preoperative echocardiography revealed severe tricuspid regurgitation resulting
      from anterior tricuspid leaflet prolapse. The patient underwent successful
      tricuspid valve repair with simple cleft suture and annuloplasty and direct
      closure of the patent foramen ovale.

PMID- 11308191
TI  - Surgical repair of superior vena cava syndrome.
AB  - We present the case of a 53-year-old woman with a history of breast cancer,
      chemotherapy, and a long-term central venous access catheter, who presented with
      acute, severe superior vena cava syndrome. Angiography showed fibrous obstruction
      of the superior vena cava with thrombosis of the innominate, both axillary
      subclavian and internal jugular veins. Surgical repair consisted of thrombectomy
      of all the involved vessels and patch repair of superior vena cava and innominate
      vein. The patient had an uneventful recovery and remains asymptomatic 12 months
      after the procedure.

PMID- 11308192
TI  - Transmitral diagnostic cardioscopy in a coronary artery bypass graft patient.
AB  - A 69-year-old man with unstable angina and impaired left ventricular function who
      was admitted for emergency coronary artery bypass grafting had echocardiographic
      findings suggestive of a left ventricular thrombus. A transmital cardioscopy was
      successfully performed at surgery, without video assistance, to confirm the
      diagnosis. We discuss our approach and the advantages.

PMID- 11308193
TI  - Left ventricular reconstruction after resection of a large fibroma.
AB  - Cardiac fibromas are rare tumors that are histologically benign but potentially
      lethal because of their location. The prognosis is related to complete resection.
      We report the case of a 15-year-old boy who, 1 year after partial excision of a
      large fibroma, underwent successful complete resection through a conventional
      surgical approach with left ventricular reconstruction.

PMID- 11308194
TI  - Fistula between a saphenous vein graft aneurysm and the pulmonary artery trunk.
AB  - We report the case of a 52-year-old man who was admitted for atypical thoracic
      pain 18 years after a saphenous vein bypass graft of the left anterior descending
      coronary artery. Investigations demonstrated an aneurysm of the middle portion of
      the vein graft with a fistulous communication to the pulmonary artery trunk. The
      aneurysm was excised surgically, and the fistula was closed with an autogenous
      pericardial patch.

PMID- 11308195
TI  - Septal dissection and rupture evolved as an inferobasal pseudoaneurysm.
AB  - We report two cases of postinfarction dissecting hematoma of the interventricular
      septum with restrictive ventricular septal defect that evolved as an inferobasal
      pseudoaneurysm. The difficult anatomical pattern was assessed by two-dimensional
      (2-D) echocardiography with Doppler and color analysis, left ventriculography and
      perioperative transoesophageal echo. Because the patient had no signs of heart
      failure, the surgical repair was successfully delayed until the dissecting tissue
      became fibrotic. Problems of diagnosis, decision making and surgical management
      are discussed.

PMID- 11308196
TI  - Myocardial abscess with contained rupture: successful repair.
AB  - Spontaneous rupture of the heart from myocardial abscess is a rare occurrence.
      Most cases of spontaneous cardiac rupture are due to myocardial infarction. We
      present a case of a contained rupture of the heart in a patient with
      staphylococcal septicemia. Although cultures from the pericardial space were
      negative the macroscopic and clinical picture was compatible with an abscess.

PMID- 11308197
TI  - Inflammatory pseudotumor of the heart causing aortic regurgitation.
AB  - Inflammatory pseudotumor is a tumor-like reactive lesion of unknown etiology that
      rarely affects the heart. We describe an unusual case of a cardiac inflammatory
      pseudotumor that involved the aortic valve and caused regurgitation in a 62-year
      old man. The lesion was excised and the aortic valve was replaced, resulting in a
      favorable outcome for the patient.

PMID- 11308198
TI  - Mycotic arch aneurysm and aortoesophageal fistula in a patient with melioidosis.
AB  - Aortoesophageal fistula due to an aortic arch aneurysm is a rare entity with an
      extremely high mortality. There are few reports of successfully managed cases and
      even fewer of long term survival. We report a case of an aortoesophageal fistula
      resulting from a mycotic pseudoaneurysm of the distal aortic arch in a patient
      with melioidosis, its surgical management, and outcome.

PMID- 11308199
TI  - Endocarditis after nipple piercing in a patient with a bicuspid aortic valve.
AB  - Piercing the skin for cosmetic reasons can be dangerous in young adults who have
      previously undergone surgery for congenital defects of the heart. We report the
      case of a 24-year-old man in whom coarctation of the aorta had been corrected 15
      years earlier. Two months after piercing his left nipple without antibiotic
      prophylaxis, he developed a local mastitis, followed by bacterial endocarditits
      that required replacement of the aortic valve.

PMID- 11308200
TI  - Fracture-embolization of duromedics valve prosthesis and microscopic uncommon
      lesions.
AB  - We report a sudden leaflet fracture of a Duromedics mitral valve 6 years after
      implantation. The patient had cardiogenic shock and complained of asthenia,
      orthopnea, and tachycardia. Transesophageal echocardiography showed the lack of
      one leaflet of the prosthesis and regurgitation. An emergency mitral replacement
      was successfully performed. Angiographic computed tomography scan localized the
      sequestrum that embolized the common iliac arteries. Examination of the deficient
      prosthesis showed multiple lesions and, in particular, a subsurface lesion that
      may be characteristic of carbon pyrolytic valves.

PMID- 11308201
TI  - Venoarterial air embolus: a complication of vacuum-assisted venous drainage.
AB  - Minimal access techniques with cardiopulmonary bypass use smaller cannula systems
      for management of cardiopulmonary bypass. To augment flow rates through the
      smaller cannula, the technique of vacuum-assisted venous drainage has been used.
      We describe a complication of vacuum-assisted venous drainage by inadvertent
      positive pressurization of the venous circuit resulting in a paradoxic air
      embolus across a patent atrial septal defect. Hazards of the current
      cardiopulmonary bypass systems and techniques for avoiding this potential
      complication are discussed.

PMID- 11308203
TI  - Pulmonary vein augmentation for single lung transplantation.
AB  - We describe a simple method of augmenting pulmonary veins using the donor
      pericardium in lung grafts which have been procured without an adequate donor
      left atrial cuff. The method allows making use of lungs procured with suboptimal
      surgical technique, such as those with short atrial cuffs or completely separated
      superior and inferior pulmonary veins. We also have applied it equally
      successfully on the right lung.

PMID- 11308202
TI  - Giant left ventricular pseudoaneurysms.

PMID- 11308204
TI  - Bentall procedure with a stentless valve and a new aortic root prosthesis.
AB  - We describe a technique to replace the aortic root by means of a stentless valve
      and a new aortic root Dacron graft (Gelweave Valsalva, Sulzer Vascutek,
      Renfrewshire, Scotland) that allows an anatomical reconstruction of the sinuses
      of Valsalva.

PMID- 11308205
TI  - Artificial mitral valve chordae replacement made simple.
AB  - Mitral valve repair techniques are now widely applied in patients with myxomatous
      valve disease. The use of artificial chords to achieve correct height adjustment
      of the prolapsing anterior leaflet segment can often be challenging. We describe
      a simple method of artificial chord reconstruction performed after annuloplasty,
      which allows for easy identification of functional prolapse and accurate chordal
      height adjustment.

PMID- 11308206
TI  - Commissure holder: an innovative device for aortic valve-sparing technique.
AB  - The key to obtaining maximal valve coaptation from the aortic valve-sparing
      procedure is in appreciating the optimal geometry of each component of the aortic
      root. We describe a new device called the Commissure Holder (patent pending) that
      aids in the selection of an appropriate graft size and in the determination of
      the optimal position at which each commissure should be sutured to the graft.

PMID- 11308207
TI  - Implantation of cardioverter device in young children: the perirenal approach.
AB  - Placement of Implantable cardioverter devices in young children is complicated
      because of the relatively large size and heavy weight of these devices. A
      technique is described where the device is implanted in the left perirenal space
      while an endovascular lead is used instead of an epicardial patch electrode.

PMID- 11308208
TI  - A new repair for anomalous left coronary artery.
AB  - We report a new technique of left coronary artery implantation to the aorta with
      interposition of a tube created from the great arterial wall for anomalous left
      coronary artery from pulmonary artery. This technique was used in 3 patients, of
      which 2 patients survived. It achieves two coronary artery repair and avoids
      problems related to extensive mobilization of coronary artery for translocation.
      It is easily reproducible.

PMID- 11308209
TI  - Leo Eloesser: an American cardiothoracic surgeon in China.
AB  - We present a brief historical vignette about one of the pioneer cardiothoracic
      surgeons, Leo Eloesser, from our personal recollections and descriptions of part
      of his long life that was spent in China. Although this article deals mainly with
      his time in China during his close association with the senior author, Dr
      Eloesser is certainly one of the most extraordinary surgeons of the 20th century.

PMID- 11308210
TI  - Anatomic and hemodynamic considerations influencing the efficiency of retrograde
      cardioplegia.
AB  - One of the major issues raised by cardiac surgical procedures requiring
      cardiopulmonary bypass is the question of myocardial protection. The preferred
      route for the administration of cardioplegia is controversial. A number of
      studies show the beneficial effects of retrograde cardioplegia but some
      demonstrate only partial or poor myocardial protection. This paper reviews the
      anatomy and anatomic variations of the coronary sinus, the coronary sinus orifice
      and cardiac veins, and the major systemic venous drainage, all of which may
      affect the distribution of retrograde cardioplegia.

PMID- 11308211
TI  - As originally published in 1990: pleural chondrosarcoma. Updated in 2001.

PMID- 11308212
TI  - As originally published in 1994: dextrorphan inhibits the release of excitatory
      amino acids during spinal cord ischemia. Updated in 2001.

PMID- 11308213
TI  - The true father of circulation: Harvey or Hippocrates?

PMID- 11308214
TI  - Excellence and low case volume.

PMID- 11308215
TI  - Preoperative intraaortic balloon pump in high-risk patients.

PMID- 11308216
TI  - Avulsion of the left internal mammary artery graft after minimally invasive
      coronary surgery.

PMID- 11308217
TI  - Autologous blood pleurodesis for treating persistent air leak after lung
      resection.

PMID- 11308218
TI  - The Bristol affair: lessons to be learned.

PMID- 11308219
TI  - Development and evaluation of sustained-release propranolol wax microspheres.
AB  - To obtain a sustained-release dosage form with a lack of gastric unwanted
      effects, wax microspheres containing propranolol (I) were prepared by a
      congealable dispersion microencapsulation technique. The effects of the process
      variables; type of wax, speed of emulsification, amount of drug loaded, type and
      amount of emulsifier, were studied on the entrapment efficiency, angle of repose,
      dissolution efficiency (DE), in-vitro drug release and mean particle size of (I)
      microspheres, by a factorial design. The results showed that changes in the
      amount of emulsifier (Tween), 0.04% and 0.08%, the type of Tween (80 and 20) and
      the wax type; beeswax or ceresine, caused a significant decrease in the
      entrapment efficiency. All the variables had an effect on the angle of repose and
      particle size of the (I) microspheres. The only significant parameter affecting
      the DE was the nature of the wax. The drug release in pH 6.8 was affected by all
      the variables except the amount of emulsifier. The formulation with a 0.25:4
      ratio of drug:ceresine wax and 0.04% of Tween 80 in 600 rpm emulsification speed
      showed a suitable multiparticulate delivery system for the retarded dissolution
      of entrapped active ingredients, allowing absorption only in the intestinal
      tract.

PMID- 11308220
TI  - Release characteristics of microspheres prepared by co-spray drying
      Actinobacillus pleuropneumoniae antigens and aqueous ethyl-cellulose dispersion.
AB  - Using formalin inactivated Actinobacillus pleuropneumoniae antigens and aqueous
      ethylcellulose dispersions, microspheres of oral vaccines were developed by a co
      spray drying process. The present study attempted to determine whether the dosage
      formulations of microspheres could form enteric matrices. To assess the enteric
      characteristics, an in vitro dissolution test was performed with the AQ6-AP
      microspheres; 95% of the A. pleuropneumoniae protein was released within 3 h at
      pH 7, but there was no release at pH 1.5. The scanning microscopy revealed that
      the surface structure of AQ6-AP microspheres became porous at neutral pH. The SDS
      PAGE analysis showed that the release rate of proteins from the microspheres was
      pH dependent not only for the AQ6-AP formulation but also when antigens of A.
      pleuropneumoniae were replaced with porcine serum. The results suggest that the
      A. pleuropneumoniae antigens were entrapped in the AQ6 microspheres under the
      acidic conditions. In a mouse model, oral immunization with AQ6-AP microspheres
      containing A. pleuropneumoniae evoked systemic IgG and mucosal IgA responses
      against A. pleuropneumoniae antigens. Thus, the present method may further
      provide an opportunity to develop oral vaccines and mucosal immunity.

PMID- 11308221
TI  - Study of processing parameters influencing the properties of diltiazem
      hydrochloride microspheres.
AB  - Diltiazem hydrochloride-ethylcellulose microspheres were prepared by the water-in
      oil emulsion-solvent evaporation technique. Small and spherical microspheres
      having a mean microsphere diameter in the range of 40-300 microm and entrapment
      efficiency of approximately 60-90% were obtained. Scanning electron micrographs
      of drug-loaded microspheres showed the presence of uniformly distributed small
      pores and absence of drug crystals on their surface, indicating simultaneous
      precipitation of drug and the polymer from the solvent during solvent
      evaporation. Differential scanning calorimetric analysis confirmed the absence of
      any drug-polymer interaction. The in vitro release profile could be altered
      significantly by changing various processing parameters to give a controlled
      release of drug from the microspheres. The stability studies of the drug-loaded
      microspheres showed that the drug was stable at storage temperatures, 5-55
      degreesC, for 12 weeks.

PMID- 11308222
TI  - Microencapsulation of theophylline in composite wall system consisting of whey
      proteins and lipids.
AB  - Theophylline was microencapsulated in composite whey protein-based wall systems
      containing different proportions of dispersed apolar filler, anhydrous milkfat.
      Wall emulsions exhibited uni-modal particle size distribution and had a mean
      particle size of 0.36-0.38 microm. Microcapsules were cross-linked by
      glutaraldehyde-saturated toluene via an organic phase. Spherical microcapsules
      ranging in diameter from 150 to larger than 700 microm were obtained and
      exhibited some surface cracks that could be attributed to the fragile nature of a
      peripheral, highly cross-linked 'shell' layer around the capsules. Core content
      ranged from 46.9-56.6% (w/w) and filler content ranged from 12.0-33.4% (w/w).
      Core and filler retention during microencapsulation ranged from 84.9-96.9%) and
      from 85.1-89.6%, respectively. Core retention was proportionally related to the
      proportion of filler embedded in the wall matrix. Core release into SGF and SIF
      was affected by microcapsule size, type of dissolution medium and wall
      composition. Rate of core release was inversely proportional to filler content of
      the wall matrix. This could be attributed to effects of filler content on
      diffusion through the wall matrix and probably on swelling properties of
      microcapsules. Results indicated that incorporation of apolar filler in wall
      matrix of whey protein-based capsules provided the means to enhance retention of
      a water-soluble core during the microencapsulation process and to decrease the
      rate of core release into aqueous dissolution media.

PMID- 11308224
TI  - Characterization of drug release from diltiazem-loaded polylactide microspheres
      prepared using sodium caseinate and whey protein as emulsifying agents.
AB  - The influence of milk protein emulsifying agents on the characteristics,
      particularly drug release, of polylactide microspheres was investigated.
      Diltiazem loaded polylactide (PL) microspheres were successfully prepared using
      the dairy proteins, sodium casinate (SC) and whey protein isolate (WPI) as the
      emulsifying agents. Microspheres were characerized in terms of microsphere yield,
      electron microscopy, particle size, drug loading, DSC and XRD analysis and drug
      release. The yields of microspheres obtained were 53-63% and were independent of
      the emulsifying agent used. SEM revealed that, regardless of the emulsifying
      agent employed, the microspheres were of good sphericity, but the surface
      appearance of the microspheres was not the same in all cases. The milk proteins
      resulted in microspheres approximately half the size of those obtained with
      methylcellulose (MC). Significant differences in drug loading were observed
      between the three emulgents, the MC systems giving the highest values. Release
      profiles were sigmoidal in shape and were well fitted to the equation ln (x/1 -
      x) = k x t - k x tmax, reflecting degradation controlled drug release. The
      parameter k increased with drug loading, while tmax decreased. The relationships
      between the release parameters [P(k and tmax)] and loading (L) could be
      quantified by equations of the form P = a x L(N), N being negative in the case of
      tmax. Apart from the effect on loading efficiency, neither SC nor WPI appeared to
      significantly alter drug release. The quantitative relationships observed in this
      study may have more general application in quantifying drug release from drug
      polymer composites at low loadings where polymer degradation controls drug
      release.

PMID- 11308223
TI  - A new method for encapsulation of living cells: preliminary results with PC12
      cell line.
AB  - A new method is described for encapsulation of living cells. PC12 rat adrenal
      pheochromocytoma cells, which have been shown to synthesize, store and release
      dopamine were employed. The particles are made first and the cells then
      incorporated in a gentle mechanical procedure. The morphology (by light and
      electron microscopic observation), stability, rheology, texture and permeability
      of these microcapsules provided by Kappa Biotech were investigated. Membrane
      permeability studies demonstrated exclusion of 69,000 Da human serum albumin, but
      equilibrium of D-glucose and inulin was within 24h, indicating a molecular weight
      cut-off in the 5000-70,000 Da range. The viability and the function of the
      encapsulated cells were evaluated by measuring the spontaneous release of
      dopamine by high performance liquid chromatography with electrochemical
      detection. The results show that dopamine-secreting cells can be sequestered in a
      semi-permeable capsule and still display good viability and proliferation for at
      least 1 month.

PMID- 11308225
TI  - Influences of process parameters on preparation of microparticle used as a
      carrier system for omega - 3 unsaturated fatty acid ethyl esters used in
      supplementary nutrition.
AB  - Microparticles were prepared by complex coacervation to encapsulate
      eicosapentaenoic acid ethyl ester (EPA-EE) for incorporation into foods as a
      nutrition supplement. Gelatin and acacia were used in the coacervation process.
      With an increasing oil/polymer ratio, both yield and encapsulation rate
      decreased; with an increasing homogenization time, the yield remained constant
      while the encapsulation rate slightly increased. Several particle hardening
      techniques were examined and their influence on particle structure, yield and
      encapsulation rate were examined. Ethanol hardening was compared to cross-linking
      with dehydroascrobic acid with respect to both yield and encapsulation rate. The
      particle diameters for both formulations were similar (ethanol: 38.4 +/- 4.1
      microm; cross-linking: 41.8 +/- 3.0 microm). Spray-drying of the coacervates led
      to the smallest particles (5.2 +/- 1.1 microm), lowest yield and encapsulation
      rate. All microencapsulation products were assayed for their storage stability
      over 4 weeks with respect to the oxidation of the encapsulated omega - 3
      unsaturated fatty acid ester inside the particles. Hardening with ethanol showed
      the lowest amount of peroxides: particle wall cross-linking by dehydroascorbic
      acid and spray-drying were observed to be less protective. All microparticles
      were characterized for their internal structure with confocal laser scanning
      microscopy (CLSM) after fluorescence labelling of the polymers, in order to
      localize the oil phase and visualize the distribution of the polymers in the
      coacervates. With increasing homogenization time, the internal structure changed
      stepwise from a capsule structure (core/wall) towards a matrix structure. For all
      experiments, a homogeneous distribution for both polymers, gelatin and acacia was
      observed inside the particle wall. No influence of the different particle
      hardening procedures on the polymer distribution was found.

PMID- 11308226
TI  - Formulation and in vitro-in vivo evaluation of piribedil solid lipid micro- and
      nanoparticles.
AB  - Modification of the dissolution rate and, thus, the enhancement of the
      bioavailability of a dopaminergic drug, piribedil, which has a low aqueous
      solubility and short elimination half-life have been the aim in this study.
      Preparations of micron and submicron particles using solid lipid carriers have
      been performed for this purpose. For the avoidance of solvent residues resulting
      from the preparation technique, cold and hot homogenization methods have been
      used to prepare solid lipid particles. After obtaining an appropriate particle
      size, piribedil loading and preparation yield by the use of those two methods,
      various formulations have been prepared with different lipid, drug and surfactant
      materials. The factors mentioned were found to affect properties of the
      particles, and the release rate was found to be the fastest in acidic medium.
      Suspensions of pure piribedil and a formulation, selected according to the
      results obtained from in vitro dissolution and particle size experiments, were
      compared using tremor tests in mice. The same suspensions were applied perorally
      to rabbits and bioavailability of the solid lipid particle was found to be higher
      than the pure piribedil. After an in vitro-in vivo evaluation of piribedil solid
      lipid particles developed for Parkinson's disease therapy, it has been determined
      that release rate could be controlled and piribedil bioavailability could be
      improved.

PMID- 11308227
TI  - Formulation of epichlorohydrin cross-linked starch microspheres.
AB  - The present work describes a water/oil emulsion technique for the production of
      microspheres by cross-linking soluble starch with epichlorohyrin, which is a very
      efficient divalent cross-linking agent for starch. Because they are important
      features for potential applications, such as pulmonary administration, special
      attention has been paid to control the mean particle size and size distribution.
      Microspheres ranging from 0.3-250 microm with narrow size distributions could be
      obtained. Due to the strongly basic nature of the aqueous phase, no stable
      emulsions could be obtained in the water/oil emulsion domains. In this context,
      the stirring rate during the emulsification step was crucial for controlling the
      particle size. Additionally, a high organic-to-aqueous phase ratio and the
      presence of a surfactant agent helped to prevent the coalescence of the droplets
      during the formation of the microspheres. The process was not sensitive to
      odifications of the chemical conditions, such as the cross-linking ratio, which
      allows variation of the chemical nature of the polymer forming the core of the
      microspheres without modifying their morphological characteristics.

PMID- 11308228
TI  - Biological cells as templates for hollow microcapsules.
AB  - Microcapsules in the micrometer size range with walls of nanometer thickness are
      of both scientific and technological interest, since they can be employed as
      micro- and nano-containers. Liposomes represent one example, yet their general
      use is hampered due to limited stability and a low permeability for polar
      molecules. Microcapsules formed from polyelectrolytes offer some improvement,
      since they are permeable to small polar molecules and resistant to chemical and
      physical influences. Both types of closed films are, however, limited by their
      spherical shape which precludes producing capsules with anisotropic properties.
      Biological cells possess a wide variety of shapes and sizes, and, thus, using
      them as templates would allow the production of capsules with a wide range of
      morphologies. In the present study, human red blood cells (RBC) as well as
      Escherichia coli bacteria were used; these cells were fixed by glutardialdehyde
      prior to layer-by-layer (LbL) adsorption of polyelectrolytes. The growth of the
      layers was verified by electrophoresis and flow cytometry, with morphology
      investigated by atomic force and electron microscopy; the dissolution process of
      the biological template was followed by confocal laser scanning microscopy. The
      resulting microcapsules are exact copies of the biological template, exhibit
      elastic properties, and have permeabilities which can be controlled by
      experimental parameters; this method for microcapsule fabrication, thus, offers
      an important new approach for this area of biotechnology.

PMID- 11308229
TI  - Encapsulation of antihypertensive drugs in cellulose-based matrix microspheres:
      characterization and release kinetics of microspheres and tableted microspheres.
AB  - This study is an attempt to prepare microspheres loaded with two antihypertensive
      drugs viz., nifedipine (NFD) and verapamil hydrochloride (VRP) using cellulose
      based polymers viz., ethyl cellulose (EC) and cellulose acetate (CA).
      Emulsification and solvent evaporation methods were optimized using ethyl acetate
      as a dispersing solvent. The particles are spherical in shape and have smooth
      surfaces, as evidenced by the scanning electron microscopy. The microspheres were
      characterized for their particle size and distribution, tapped density and
      encapsulation efficiency. Smaller sized particles with a narrow size distribution
      were produced with EC when compared to CA matrices. Molecular level drug
      distribution in the microspheres was confirmed by differential scanning
      calorimetry. The microspheres were directly compressed into tablets using
      different excipients. The drug release from CA was faster than EC microspheres
      and, also, the VRP release was faster than NFD. The excipients used in tableting
      showed an effect on the release as well as the physical properties of the
      tablets.

PMID- 11308230
TI  - Literature Alerts.

PMID- 11308231
TI  - Total parenteral nutrition in the surgical patient: a meta-analysis.
AB  - OBJECTIVE: To examine the relationship between total parenteral nutrition(TPN)
      and complication and death rates in surgical patients. DATA SOURCES: A computer
      search of published research on MEDLINE, personal files and a review of relevant
      reference lists. STUDY SELECTION: A review of 237 titles, abstracts or papers.
      Primary studies were included if they were randomized clinical trials of surgical
      patients that evaluated the effect of TPN (compared to no TPN or standard care)
      on complication and death rates. Studies comparing TPN to enteral nutrition (EN)
      were excluded. DATA EXTRACTION: Relevant data were abstracted on the methodology
      and outcomes of primary studies. Data were independently abstracted in duplicate.
      DATA SYNTHESIS: There were 27 randomized trials in surgical patients that
      compared the use of TPN to standard care (usual oral diet plus intravenous
      dextrose). When the results of these trials were aggregated, there was no effect
      on mortality (risk ratio = 0.97, 95% confidence intervals, 0.76 to 1.24). There
      were fewer major complications in patients who received TPN, although there was
      significant heterogeneity in the overall estimate (risk ratio = 0.81, 95% CI,
      0.65 to 1.01). Because of this significant heterogeneity, several a priori
      hypotheses were examined. Studies that included only malnourished patients
      demonstrated a trend to a reduction in complication rates but no difference in
      death rate when compared with studies of patients who were not malnourished.
      Studies published in 1988 or earlier and studies with a lower methods score were
      associated with a significant reduction in complication rates and a trend to a
      reduction in death rate when compared with studies published after 1988 and
      studies with a higher methods score. There was no difference in studies that
      provided lipids as a component of TPN when compared with studies that did not.
      Studies that initiated TPN preoperatively demonstrated a trend to a reduction in
      complication rates but no difference in death rate when compared with studies
      that initiated TPN postoperatively. CONCLUSIONS: TPN does not influence the death
      rate of surgical patients. It may reduce the complication rate, especially in
      malnourished patients, but study results are influenced by methodologic quality
      and year of publication.

PMID- 11308232
TI  - Glutaraldehyde-induced colitis.
AB  - OBJECTIVE: To describe the etiology and clinical course of acute colitis
      occurring after flexible endoscopy. DESIGN: Chart review. SETTING: A university
      teaching hospital. PATIENTS: Eight patients who sought assessment of potential
      colonic disease. INTERVENTION: Colonoscopy in 5 patients and flexible
      sigmoidoscopy in 3 patients. The indication for endoscopy was screening in 5
      patients, cancer surveillance in 2 patients and preoperative evaluation of colon
      carcinoma in 1 patient. OUTCOME MEASURES: The relation of presenting symptoms to
      glutaraldehyde exposure, the response to therapy and the need for further
      therapy. RESULTS: All patients had abdominal pain, mucus diarrhea and rectal
      bleeding within 48 hours after endoscopy. Most patients reported that the
      symptoms started within 12 hours of the procedure. All patients were confirmed by
      sigmoidoscopy to have colitis within 72 hours of the first endoscopic procedure.
      One patient required hospitalization. In the first 7 patients several stool
      cultures were negative for Clostridium difficile using the cytotoxin assay by the
      cell culture method. Four patients had negative cultures for Yersinia, Salmonella
      and Shigella spp. Three patients were treated with metronidazole initially. Two
      patients underwent endoscopic biopsy and examination of the biopsy specimen
      showed fibrinoleukocytic exudate and ischemic type injury. One patient underwent
      the scheduled sigmoid resection within 48 hours of endoscopy for a Dukes' stage B
      adenocarcinoma. Concomitant acute ischemic colitis limited to the mucosa and
      submucosa was noted in the resected specimen. Symptoms resolved in all patients
      and follow-up endoscopy revealed normal mucosa. CONCLUSION: The entity of
      glutaraldehyde-induced colitis should be recognized and special attention should
      be given during instrument cleansing to minimize the risk of its development.

PMID- 11308233
TI  - Cost factors in Canadian pediatric trauma.
AB  - OBJECTIVES: To estimate the costs of Canadian pediatric trauma and identify cost
      predictors. DESIGN: A chart review. SETTING: A regional trauma centre. STUDY
      MATERIAL: The charts of all 221 children who suffered traumatic injuries with an
      Injury Severity Score (ISS) of 4 or more seen over 6 years at a regional trauma
      centre. MAIN OUTCOME MEASURES: Patient data, injury data, all hospital-based
      costs, excluding nursing, food and medication costs. RESULTS: Mean (and standard
      deviation) patient age was 12.8 (5) years. Sixty percent were boys. Motor vehicle
      accidents (MVAs) accounted for 71% of the injuries, followed by falls (11%). The
      mean (and SD) total cost of care was Can$7,582 (Can$12,370), and the cost of
      media was Can$2,666. Total cost correlated directly with age (r = 0.29, p <
      0.001) and Injury Severity Score (ISS) (r = 0.34, p < 0.001) and inversely with
      the Pediatric Trauma Score (PTS) (r = -0.20, p = 0.003). The presence of
      extremity injuries correlated significantly with total cost (r = 0.22, p = 0.001)
      and PTS (r = -0.25, p < 0.001) but not with the ISS. Logistic regression analysis
      identified runk injury, ISS and PTS as the main determinants of survival.
      CONCLUSIONS: The cost of pediatric trauma in Canada can be predicted from
      admission data and trauma scores. The cost of extremity injuries is significant
      and can be predicted by the PTS but not the ISS.

PMID- 11308234
TI  - Infected urachal cyst.

PMID- 11308235
TI  - Penetrating neck injuries: analysis of experience from a Canadian trauma centre.
AB  - OBJECTIVE: To study the demographics and treatment outcome of penetrating neck
      injuries presenting to a major trauma centre in order to develop a treatment
      protocol. DESIGN: A case review. SETTING: A trauma centre at a tertiary care
      institution. PATIENTS: One hundred and thirty consecutive patients who had 134
      neck wounds penetrating the platysma and presented to the trauma service between
      1979 and 1997. INTERVENTION: Surgical exploration or observation alone. MAIN
      OUTCOME MEASURES: The location of injury, patient management, number of
      significant injuries, duration of hospital stay and outcome. RESULTS: Injuries
      were caused by stab wounds in 124 patients (95%) and gunshot wounds in 6 (5%).
      The location of injury was zone I (lower neck) in 20 cases (15%), zone II
      (midportion of the neck) in 108 (81%) and zone III (upper neck) in 5 (4%). The
      location was not recorded in 1 case. Fifty patients were managed by observation
      alone and 80 were managed surgically. Neck exploration in 48 asymptomatic
      patients was negative in 32 (67%). Significant injuries, including major vascular
      (12), nerve (13) and aerodigestive tract (19) injuries, were identified in 34
      patients. Two of the 130 patients (1.5%) died of major vascular injuries. Seventy
      six percent of significant injuries, including all zone II major vascular
      injuries, were symptomatic on presentation. The mean (and standard deviation)
      hospital stay for asymptomatic patients treated with observation alone and
      surgical exploration was similar (3.5 [6.02] versus 4.3 [5.46] days respectively,
      p = 0.575). Long-term disability, all neurologic in nature, was documented in 3
      patients managed by observation alone and 6 patients managed by surgical
      exploration. CONCLUSIONS: Penetrating neck trauma, in particular stab wounds to
      zone II in asymptomatic patients, is associated with low morbidity and mortality.
      A selective management protocol with investigations directed by symptoms is the
      most appropriate approach for the patient population and resource base in this
      setting.

PMID- 11308236
TI  - Effect of femoral component designs on the contact and tracking characteristics
      of the unresurfaced patella in total knee arthroplasty.
AB  - OBJECTIVES: To determine the effect of 5 different femoral components used in
      total knee arthroplasty (TKA) on the contact area and tracking characteristics of
      the nonresurfaced patella and to identify any design features that might
      adversely affect these characteristics. DESIGN: An in-vitro study. SETTING: The
      biomechanics laboratory, Department of Mechanical Engineering, McGill University,
      Montreal. SPECIMENS: Six fresh-frozen cadaveric knee-joint specimens.
      INTERVENTIONS: An unconstrained quadriceps simulator was used to apply the
      conditions of static lifting to the specimens first in their normal state and
      then sequentially implanted with femoral and tibial components of various designs
      (Miller/Galante II, Anatomic Modular Knee [AMK] System, Whiteside Ortholoc
      Modular, press-fit condylar and Insall-Burstein II). OUTCOME MEASURES: Patellar 3
      dimensional tracking characteristics, determined by using a 6 degrees-of-freedom
      electromechanical goniometer attached directly to the patella, and patellar
      contact pressure measurements, obtained using low-range Fuji Prescale film.
      RESULTS: Articulation of the normal patella on a prosthetic femoral component
      resulted in alterations in the normal patellofemoral contact and tracking
      characteristics. The exact departure depended on the design of the prosthetic
      trochlea. Although all of the selected prostheses demonstrated satisfactory
      contact characteristics near extension, marked alterations occurred at higher
      flexion angles. With 90 degrees or more of flexion, there was incompatibility
      between the geometries of the prosthetic notch of 2 femoral designs (AMK and PFC)
      and the normal knee. CONCLUSION: The design of the prosthetic femoral component
      must be taken into account when determining whether or not to resurface the
      patella at the time of TKA.

PMID- 11308237
TI  - Yersinia enterocolitica as a cause of intra-abdominal abscess: the role of iron.

PMID- 11308238
TI  - The promised land.

PMID- 11308239
TI  - Length of surgical residency programs.

PMID- 11308240
TI  - Evolving questions of perioperative nutritional support.

PMID- 11308241
TI  - Musculoskeletal images. Clavicular soft-tissue mass.

PMID- 11308242
TI  - Soft-tissue images. Portal vein thrombosis and gas formation: unusual
      presentation of colon cancer.

PMID- 11308243
TI  - Musculoskeletal case 15. Presentation. Marfan's syndrome.

PMID- 11308244
TI  - Soft-tissue case 38. Presentation. Mycotic aneurysm of the abdominal aorta.

PMID- 11308245
TI  - Users' guide to evidence-based surgery: how to use an article evaluating surgical
      interventions. Evidence-Based Surgery Working Group.

PMID- 11308246
TI  - Psychiatric morbidity and its recognition by doctors in patients with cancer.
AB  - Psychiatric morbidity in patients with cancer is high and without appropriate
      treatment unremitting. We assessed the ability of 143 doctors to establish the
      psychological status of 2297 patients during outpatient consultations in 34
      cancer centres and hospitals in the UK. Prior to seeing the doctor, consenting
      patients completed a short self-report questionnaire (GHQ12), designed for the
      psychological screening of large populations. At the end of the consultation,
      doctors completed visual analogue scales rating patients' distress. 837/2297
      (36.4%) patients had GHQ scores suggestive of psychiatric morbidity. The doctors'
      sensitivity (true positive rate) was 28.87% (SD 25.29), specificity (true
      negative rate) 84.79% (SD 17.44). The misclassification rate was 34.7% (SD 13.79)
      meaning that for 797 patients the wrong assessment was probably made. These data
      show that much of the probable psychiatric morbidity experienced by patients with
      cancer goes unrecognized and therefore untreated. Doctors need communication
      skills training to elicit problems during consultations. Appropriate referrals to
      psychological services are necessary when patients requiring help are identified
      and ought to be an integral part of cancer care.

PMID- 11308247
TI  - Evaluation of total choline from in-vivo volume localized proton MR spectroscopy
      and its response to neoadjuvant chemotherapy in locally advanced breast cancer.
AB  - Results of the proton magnetic resonance spectroscopy carried out on normal,
      benign breast disease and locally advanced breast cancer patients are presented.
      The in-vivo MR spectra of malignant breast tissue of patients (n = 67) suffering
      from infiltrating ductal carcinoma are dominated by the water resonance, while
      the spectra of the unaffected contralateral breast tissue of these patients are
      mainly dominated by resonance arising from lipids which is similar to the spectra
      of normal breast tissue obtained from volunteers (controls, n = 16). In addition
      to the water and lipid peaks, in majority of the patients (approximately 80%) the
      water suppressed spectra showed a resonance at 3.2 ppm due to choline containing
      compounds (TCho) before treatment. In patients receiving neoadjuvant
      chemotherapy, absence/reduction in choline was observed in 89% of the patients.
      TCho was also observed in 2 of 14 benign lesions. The sensitivity and specificity
      of in-vivo MRS in detecting TCho in malignant tumours was 78% and 86%,
      respectively. Observation of TCho before treatment and its disappearance (or
      reduction) after treatment may be a useful indicator of response of locally
      advanced breast cancer to neoadjuvant chemotherapy.

PMID- 11308248
TI  - 5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly
      effective, low-cost chemotherapy for advanced colorectal cancer.
AB  - We have reported that an alternating regimen of bolus and continuous infusion 5
      fluorouracil (FU) was superior to bolus FU in terms of response rate and
      progression-free survival in advanced colorectal cancer. Biochemical modulation
      was an essential part of this regimen and it was selective for the schedule of FU
      administration: bolus FU was in fact modulated by methotrexate (MTX) while
      continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the
      low cost and the favourable report on the activity of mitomycin C (mito) added to
      CI FU, we have incorporated this agent in the infusional part of our treatment
      programme. 105 patients with untreated, advanced, measurable colorectal cancer
      were accrued from 13 Italian centres and treated with the following regimen. 2
      biweekly cycles of FU bolus (600 mg/m(2)), modulated by MTX (24 h earlier, 200
      mg/m(2)) were alternated with a 3-week continuous infusion of FU (200
      mg/m(2)daily), modulated by LV (20 mg/m(2)weekly bolus). Mito, 7 mg/m(2), was
      given on the first day of the infusional period. After a 1 week rest, the whole
      cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses
      were obtained (response rate, 37% on the intention to treat basis; 95% confidence
      limits, 28-46%). After a median follow-up time of 26 months, 37 patients are
      still alive. The median progression-free survival is 7.7 months with an overall
      survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very
      well tolerated with fewer than 13% of patients experiencing WHO grade III-IV
      toxicity. These results are consistent with those obtained by our group in 3
      previous trials of schedule specific biochemical modulation of FU. They also
      indicate a highly active, little toxic, inexpensive regimen of old drugs to be
      used (a) as an alternative to the more expensive combinations including CPT-11 or
      oxaliplatin or (b) as the basis for combination programmes with these agents.

PMID- 11308249
TI  - A phase I study in paediatric patients to evaluate the safety and
      pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.
AB  - Pre-clinical studies indicate that cisplatin encapsulated in
      STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much
      reduced toxicity, compared to native cisplatin. A phase I study was conducted to
      determine the toxicity and pharmacokinetics of SPI-77 administered to children
      with advanced cancer not amenable to other treatment. Paediatric patients were
      treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4
      weeks. Blood samples taken during, and up to 3 weeks after, administration and
      plasma and ultrafiltrate were prepared immediately. Urine was collected, when
      possible, for 3 days after administration. SPI-77 administration was well
      tolerated with the major toxicity being an infusion reaction which responded to
      modification of the initial infusion rate of SPI-77. Limited haematological
      toxicity and no nephrotoxicity were observed. No responses to treatment were seen
      during the course of this phase I study. Measurement of total plasma platinum
      showed that cisplatin was retained in the circulation with a half life of up to
      134 h, with maximum plasma concentrations approximately 100-fold higher than
      those reported following comparable doses of cisplatin. Comparison of plasma and
      whole blood indicated that cisplatin was retained in the liposomes and there was
      no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4%
      of the dose administered over 72 h. Results from this phase I study indicate that
      high doses of liposomal cisplatin can safely be given to patients, but further
      studies are required to address the issue of reformulation of liposomally bound
      cisplatin.

PMID- 11308250
TI  - Dacarbazine and interferon alpha with or without interleukin 2 in metastatic
      melanoma: a randomized phase III multicentre trial of the Dermatologic
      Cooperative Oncology Group (DeCOG).
AB  - In several phase II-trials encouraging tumour responses rates in advanced
      metastatic melanoma (stage IV; AJCC-classification) have been reported for the
      application of biochemotherapy containing interleukin 2. This study was designed
      to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha
      (IFN-alpha) only to that of therapy with DTIC and IFN-alpha with the addition of
      interleukin 2 (IL-2) in terms of the overall survival time and rate of objective
      remissions and to provide an elaborated toxicity profile for both types of
      therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2)every 28
      days) plus IFN-alpha2a/b (3 MIU/m(2), twice on day 1, once daily from days 2 to
      5; 5 MIU/m(2)3 times a week from week 2 to 4) with or without IL-2 (4.5
      MIU/m(2)for 3 hours i.v. on day 3; 9.0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c.
      days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of
      therapy) for every patient. Of 290 randomized patients 281 were eligible for an
      intention-to-treat analysis. There was no difference in terms of survival time
      from treatment onset between the two arms (median 11.0 months each). In 273
      patients treated according to protocol tumour response was assessable. The
      response rates did not differ between both arms (P = 0.87) with 18.0% objective
      responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8%
      PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse
      reactions was significantly more common in patients receiving IL-2 (13.9%) than
      in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was
      neither a difference in survival time nor in tumour response rates when IL-2,
      applied according to the combined intravenous and subcutaneous schedule used for
      this study, was added to DTIC and IFN-alpha. However, toxicity was increased in
      melanoma patients treated with IL-2. Further phase III trials with continuous
      infusion and higher dosages must be performed before any final conclusions can be
      drawn on the potential usefulness of IL-2 in biochemotherapy of advanced
      melanoma.

PMID- 11308251
TI  - Topotecan given as a 21-day infusion in the treatment of advanced ovarian cancer.
AB  - A phase II programme was carried out in both Europe and North America to evaluate
      the activity of topotecan administered as a 21-day continuous intravenous
      infusion to patients with recurrent ovarian cancer. The European results are
      reported here. Patients who had failed first line therapy with a platinum-based
      regimen received topotecan 0.4 mg/m(2)/day, as a 21-day infusion every 28 days.
      Patients were only permitted one prior regimen. 35 patients were enrolled and
      evaluable for response. 3 patients (8.6%) had a partial response to treatment
      (95% CI 1.8%, 23.1%) with a median time to response of 8.1 weeks and a median
      duration of response of 17.6 weeks. Response was also evaluated by CA125 and was
      also found to be 8%. For all 35 patients, median time to progression was 16.1
      weeks and median survival was 43.6 weeks. The principal toxicity was
      myelosuppression although grade 4 neutropenia occurred in only 8.8% of patients
      (2.1% of courses) and infectious complications were relatively infrequent. Non
      haematological toxicity was generally mild and mainly consisted of
      gastrointestinal events, alopecia and fatigue. A prolonged infusion of topotecan
      was well tolerated with a low incidence of severe neutropenia. Responses were
      seen in both North American and European patients. Response rates varied between
      the 2 studies possibly due to differences in patient demographics.

PMID- 11308252
TI  - The effect of clodronate and antioestrogens on bone loss associated with
      oestrogen withdrawal in postmenopausal women with breast cancer.
AB  - In this study we report bone mineral density (BMD) changes during clodronate and
      antioestrogen treatment in women with breast cancer having discontinued hormone
      replacement therapy (HRT) at the time of operation compared to women who had not
      used HRT immediately before the operation. 61 postmenopausal women with operable
      breast cancer were treated with the adjuvant antioestrogen tamoxifen 20 mg or
      toremifene 60 mg daily for 3 years. All patients were randomized to clodronate
      (1.6 g daily orally) or control groups for 3 years. 23 patients had recently
      (recent users) and 38 never or not for at least 1 year before operation used HRT
      (non-users). BMD of lumbar spine and femoral neck were measured before
      antiresorptive therapy (antioestrogens and clodronate) and at 1, 2, 3 and 5 years
      thereafter. All patients were disease-free at the time of BMD measurements.
      Patients who had recently used HRT had more significant bone loss as compared to
      HRT non-users at 3 years in lumbar spine - 3.0% vs. + 1.2% (P< 0.001), but not in
      femoral neck - 0.4% vs. + 1.7% (P = 0.27). Adding 3-year clodronate treatment to
      antioestrogen therapy improved BMD marginally at 3 years: lumbar spine + 1.0% vs.
      -1.7% (P = 0.01) and femoral neck + 2.4% vs. -0.4% (P = 0.12). This was also seen
      at 5 years of follow-up, 2 years after termination of the antiresorptive therapy:
      HRT recent users vs. HRT non-users in lumbar spine -6.5% vs. +0.5% (P< 0.0001)
      and in femoral neck -4.8% vs. -1.5% (P = 0.38); and clodronate vs. controls in
      lumbar spine -1.0% vs. -3.2% (P = 0.06) and in femoral neck -0.1% vs. -5.2% (P =
      0.001, respectively). The type of endocrine therapy (tamoxifen and toremifene)
      had no significant influence on BMD changes. We conclude from this study that
      postmenopausal women who have recently discontinued HRT experience more rapid
      bone loss than HRT non-users. Neither 3-year antioestrogen therapy alone nor
      antioestrogen together with clodronate could totally prevent the bone loss
      related to HRT withdrawal in lumbar spine, even though clodronate seemed to
      retard it.

PMID- 11308253
TI  - Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide
      derived from wild-type p53.
AB  - Mutations in the p53 gene are the most common genetic alterations found in human
      tumours, and these mutations result in high levels of p53 protein in the tumour
      cells. Since the expression levels of wild-type p53 in nonmalignant tissue are
      usually much lower in contrast, the p53 protein is an attractive target for
      cancer immunotherapy. We tested p53 encoded HLA-A24 binding peptides for their
      capacity to elicit anti-tumour cytotoxic T lymphocytes (CTL) in vitro. These
      peptides were in murine p53-derived cytotoxic peptides, which were being
      presented to CTL by H-2K(d)and H-2K(b)molecules, because the HLA-A24 peptide
      binding motifs were similar to the H-2K(d)and H-2K(b). For CTL induction, we used
      CD8(+)T lymphocytes from the peripheral blood mononuclear cells (PBMC) of healthy
      donors and the peptides from pulsed dendritic cells as antigen-presenting cells.
      We identified the peptide, p53-161 (AIYKQSQHM), which was capable of eliciting
      CTL lines that lysed tumour cells expressing HLA-A24 and p53. The effectors lysed
      C1RA24 cells (p53(+), HLA-A*2402 transfectant), but not their parental cell lines
      C1R (p53(+), HLA-A,B null cell). These results strongly indicate that the CTL
      exerts cytotoxic activity in HLA-A24's restricted manner. The identification of
      this novel p53 epitope for CTL offers the possibility to design and develop
      specific immunotherapeutic approaches for treating tumours with p53 mutation in
      HLA-A24-positive patients.

PMID- 11308254
TI  - Variation in the E2-binding domain of HPV 16 is associated with high-grade
      squamous intraepithelial lesions of the cervix.
AB  - Human papillomaviruses (HPV) are strongly associated with cervical
      intraepithelial neoplasia (CIN) and invasive cancer mainly through the action of
      the E6 and E7 viral proteins, transcription of which is down-regulated by the E2
      protein. To test the hypothesis that HPV 16 E2 variation is important in the
      development of high-grade squamous neoplasia of the cervix, we carried out a
      cross-sectional analysis of low-grade and high-grade squamous intraepithelial
      lesions (SILs) for specific mutations in the HPV 16 E2 gene and for E2 gene
      disruption in these regions. Isolates were also analysed for the HPV 16 350T-G
      variant. 22 of 178 low-grade SILs and 43 of 61 high-grade SILs examined,
      contained HPV 16. No relationship was found between the E6 350T-G variant, or the
      E2 hinge region 3410C-T variant, and lesion grade. However, disruption of the
      regions of E2 analysed was significantly more frequent in high-grade lesions, and
      there was a significant association between the 3684C-A variant in the E2 DNA
      binding domain and high-grade histology suggesting that this variant may be
      important in progression to high-grade intraepithelial disease.

PMID- 11308255
TI  - Immunodetectable cyclin D(1)is associated with oestrogen receptor but not Ki67 in
      normal, cancerous and precancerous breast lesions.
AB  - Cyclin D1 is associated with cell cycle regulation and has more recently been
      shown to stimulate the transcriptional functions of the oestrogen receptor (ER).
      Furthermore, in normal breast there is a negative association between expression
      of ER and the proliferation marker Ki67 indicating that either ER positive cells
      are non-dividing or that the receptor is down-regulated as cells enter cycle.
      This important relationship breaks down in many ER-positive cancers and
      precancerous breast lesions where the receptor is often detected on proliferating
      cells. The aims of the present study were to determine the interplay between ER,
      Ki67 and cyclin D(1)in individual cells within the spectrum of human breast
      lesions ranging from normal to invasive carcinoma by using dual staining
      immunofluorescence. We found that in normal breast there was a strong positive
      association between ER and cyclin D(1)expression. In contrast there was a strong
      negative association between cyclin D(1)and Ki67 expression. Similar findings
      were seen for the other precancerous and cancerous breast lesions. Thus
      immunodetectable cyclin D(1)within individual cells does not appear to be
      associated with cell cycle progression in the benign or malignant breast but
      instead may have important interactions with ER.

PMID- 11308256
TI  - Hypoxia in human soft tissue sarcomas: adverse impact on survival and no
      association with p53 mutations.
AB  - Clinical and experimental studies have suggested that tumour hypoxia is
      associated with poor treatment outcome and that loss of apoptotic potential may
      play a role in malignant progression of neoplastic cells. The tumour suppressor
      gene p53 induces apoptosis under certain conditions and microenvironmental tumour
      hypoxia may select for mutant tumour cells with diminished apoptotic potential
      due to lack of p53 function. The aim of this study was to evaluate the prognostic
      relevance of oxygenation status for treatment outcome and to compare pre
      treatment tumour oxygenation measurements were done in 31 of those by PCR using
      DNA extracted from paraffin-embaedded sections (n = 2) or frozen biopsies (n =
      29). The overall median of the tumour median pO(2)was 19 mmHg (range 1-58 mmHg).
      Only 6 tumours had functional p53 mutations and no association was found between
      mutant p53 and tumour hypoxia. Five out of 6 STS with lower histopathological
      grade were well-oxygenated whereas high-grade STS were both hypoxic and well
      oxygenated. At a median follow-up of 74 months, 16 patients were still alive
      among 28 available for survival analysis. When stratifying into hypoxic and well
      oxygenated tumours patients with the most hypoxic tumours has a statistically
      poorer disease-specific and overall survival at 5 years. In conclusion hypoxia
      was an indicator for both a poorer disease specific and overall survival in human
      STS but hypoxic tumours were not characterized by mutations in the p53 gene.

PMID- 11308258
TI  - Role of chance in familial aggregation of colorectal cancer.
AB  - A prospective population-based study recorded family trees of 77 colorectal
      cancer patients younger than 50 years of age. Using mathematical modeling of
      population age-incidence data, we estimate that 1 (95% confidence limits 0 and 3)
      of these families is expected to meet the Amsterdam criteria I for HNPCC due to
      chance clustering of colorectal cancer.

PMID- 11308257
TI  - Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ
      cultured prostate tissue: levels of collagenolytic and gelatinolytic MMPs are
      low, variable and different in fresh tissue versus organ-cultured tissue.
AB  - Prostate tissue was obtained from 22 radical prostatectomies (performed for
      clinical management of prostate carcinoma) immediately after surgery. A small
      piece of tissue was fixed immediately in formalin and used for routine histology
      while a second piece was frozen in OCT and used for immuno-histochemistry.
      Another small piece was used for isolation of epithelial and stromal cells. The
      remainder of the tissue was cut into 2 x 2 mm pieces and incubated in organ
      culture for 8 days. In organ culture, non-malignant, basal epithelial cells
      underwent a proliferative response. This was accompanied by de-differentiation of
      glandular structures and by migration of epithelial cells across the surface of
      the tissue. Erosion of the basement membrane could also be seen in places, but
      was not widespread. Invasion of epithelial cells into the adjacent stroma was not
      evident. Production of matrix metalloproteinases (MMPs) with gelatinolytic
      activity or collagenolytic activity was assessed in organ culture and compared to
      expression patterns in fresh tissue. MMP-1 (interstitial collagenase) and MMP-9
      (92-kDa gelatinase B) were undetectable or low in fresh tissue specimens. Both
      enzymes were detected in organ culture and both increased over time. Even after 6
      days, however, there was only a low level of gelatin-hydrolytic activity and no
      measurable collagen-hydrolytic activity. In past studies we used organ cultures
      of normal skin and malignant skin tumours (basal cell carcinomas) to help
      elucidate the role of collagenolytic and gelatinolytic MMPs in epithelial cell
      invasion (Varani et al, 2000). Compared to MMP levels observed in skin, levels of
      these enzymes in prostate are low. The low level of collagenolytic and
      gelatinolytic MMPs in fresh prostate tissue and in organ-cultured prostate tissue
      may help explain why there is little tissue destruction in many primary prostate
      tumours and why the majority of such tumours remain confined to the prostate for
      extended periods.

PMID- 11308259
TI  - Identification of a novel spliced variant of the SYT gene expressed in normal
      tissues and in synovial sarcoma.
AB  - Synovial sarcoma (SS) is cytogenetically characterized by the translocation
      t(X;18)(p11.2-q11.2) generating a fusion between the SYT gene on chromosome 18
      and one member of the SSX family gene (SSX1; SSX2; SSX4) on chromosome X. Here,
      we report for the first time that 2 forms of SYT mRNA are present in both normal
      tissues and SSs. By amplifying the full-length SYT cDNA of two SSs, we detected 2
      bands, here designated N-SYT and I-SYT. The latter, previously undescribed,
      contains an in-frame insertion of 93 bp. Its sequencing revealed a 100% homology
      with the mouse SYT gene. These two SYT forms were present, although in different
      amounts, in all human normal tissues examined, including kidney, stomach, lung,
      colon, liver and synovia. Coexistence of N-SYT and I-SYT (both fused with SSX)
      was detected in a series of 59 SSs (35 monophasic and 24 biphasic) and in a SS
      cell line. A preliminary analysis of the differential expression levels of N-SYT
      and I-SYT in SSs revealed that the latter was consistently overexpressed,
      suggesting a role in SS pathogenesis.

PMID- 11308260
TI  - Immunohistochemical detection of ERbeta in breast cancer: towards more detailed
      receptor profiling?
AB  - Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in
      patients with breast cancer. A second ER, ERbeta has been described but its
      significance remains undefined; most studies have described mRNA levels rather
      than protein expression. Here, we demonstrate for the first time,
      immunohistochemical detection of ERbeta in archival breast tumours.

PMID- 11308261
TI  - Dissociation of mitochondrial depolarization from cytochrome c release during
      apoptosis induced by photodynamic therapy.
AB  - Photodynamic therapy (PDT) with the phthalocyanine photosensitizer Pc 4 induces
      rapid apoptosis in mouse lymphoma (LY-R) cells, initiating with the release of
      cytochrome c from mitochondria. It has been proposed that the opening of the
      mitochondrial membrane permeability transition pores, which results in the
      dissipation of the mitochondrial membrane potential (Deltapsi(m)), is essential
      for the escape of cytochrome c from mitochondria into the cytosol as well as for
      apoptotic cell death. Therefore, we have assessed the correlation between the
      loss of Deltapsi(m)and the release of cytochrome c following PDT. Treatment of LY
      R cells with 300 nM Pc 4 and 60, 90 or 120 mJ/cm(2)of red light resulted in
      apoptosis of 80-90% of the cells, accompanied by >20-fold elevation in caspase-3
      like activity within one h. At all 3 doses of PDT employed here, the majority of
      the cytochrome c was released from mitochondria at 15 min after irradiation, as
      determined by an immunohistochemical method. In contrast, the loss of
      Deltapsi(m)following PDT, as monitored by the uptake of JC-1 or Rh-123, depended
      on the PDT dose and the post-treatment time. In spite of the release of
      cytochrome c at 15 min after each of the 3 doses, a corresponding loss of
      Deltapsi(m)was observed only for those cells that received the highest dose of
      PDT. Virtually all cells that received one of the lower doses of PDT (300 nM Pc 4
      plus 60 or 90 mJ/cm(2)) maintained normal Deltapsi(m). Hence, our results support
      the conclusion that the release of cytochrome c from mitochondria resulting from
      Pc 4-PDT-induced photodamage is independent of the loss of Deltapsi(m).
      Therefore, it is important to consider a range of doses of this or other
      apoptotic stimuli in deciphering the relationship of metabolic responses that
      contribute to apoptosis.

PMID- 11308262
TI  - N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental
      mouse brain tumours.
AB  - Abnormalities in glycosphingolipid (GSL) biosynthesis have been implicated in the
      oncogenesis and malignancy of brain tumours. GSLs comprise the gangliosides and
      the neutral GSLs and are major components of the cell surface glycocalyx. N 
      butyldeoxynojirimycin (N B-DNJ) is an imino sugar that inhibits the
      glucosyltransferase catalysing the first step in GSL biosynthesis. The influence
      of N B-DNJ was studied on the growth and ganglioside composition of two 20
      methylcholanthrene-induced experimental mouse brain tumours, EPEN and CT-2A,
      which were grown in vitro and in vivo. N B-DNJ (200 microM) inhibited the
      proliferation of the EPEN and CT-2A cells by 50%, but did not reduce cell
      viability. The drug, administered in the diet (2400 mg kg(-1)) to adult syngeneic
      C57BL/6 mice, reduced the growth and ganglioside content of subcutaneous and
      intracerebral EPEN and CT-2A tumours by at least 50% compared to the untreated
      controls. N B-DNJ treatment also shifted the relative distribution of tumour
      gangliosides in accordance with the depletion of metabolic substrates. Side
      effects of N B-DNJ treatment were generally mild and included reductions in body
      and spleen weights and intestinal distension. We conclude that N B-DNJ may
      inhibit tumour growth through an effect on ganglioside biosynthesis and may be
      useful as a new chemotherapy for brain tumours.

PMID- 11308263
TI  - Characterization of BIS20x3, a bi-specific antibody activating and retargeting T
      cells to CD20-positive B-cells.
AB  - This paper describes a bi-specific antibody, which was called BIS20x3. It
      retargets CD3varepsilon-positive cells (T-cells) to CD20-positive cells and was
      obtained by hybrid-hybridoma fusion. BIS20x3 could be isolated readily from
      quadroma culture supernatant and retained all the signalling characteristics
      associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads
      to DNA fragmentation percentages similar to those obtained after Rituximab-cross
      linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab')2
      fragments induced T-cell activation. Indirect cross-linking of T-cell-bound
      BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was
      demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to
      high B-cell cytotoxicity. The results presented in this paper show that BIS20x3
      is fully functional in retargeting T-cells to B-cells and suggest that B-cell
      lymphomas may represent ideal targets for T-cell retargeting bi-specific
      antibodies, because the retargeted T-cell is maximally stimulated in the presence
      of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon
      binding of CD20-directed antibodies, B-cells will become even more sensitive for
      T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to
      use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell
      malignancies as a treatment modality for these diseases.

PMID- 11308264
TI  - Chronic hypoxia modulates tumour cell radioresponse through cytokine-inducible
      nitric oxide synthase.
AB  - Chronic hypoxia up-regulated the mRNA and protein expression of inducible nitric
      oxide synthase (iNOS) in EMT-6 tumour cells exposed to interferon (IFN)-gamma and
      interleukin (IL)-I beta. Low concentrations of cytokines (1 unit ml(-1)) in 1%
      but not in 21% oxygen induced a remarkable increase in NO production and a 1.8
      fold hypoxic cell radiosensitization. Therefore, chronic hypoxia may potentially
      be exploited to increase tumour cell radioresponse through the cytokine-inducible
      iNOS pathway.

PMID- 11308265
TI  - The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells:
      evidence for synergy with paclitaxel.
AB  - Bisphosphonates are well established in the management of breast-cancer-induced
      bone disease. Recent studies have suggested that these compounds are effective in
      preventing the development of bone metastases. However, it is unclear whether
      this reflects an indirect effect via an inhibition of bone resorption or a direct
      anti-tumour effect. The breast cancer cell lines, MCF-7 and MDA-MB-231 cells were
      treated with increasing concentrations of the bisphosphonate, zoledronic acid,
      for varying time periods, in the presence or absence of paclitaxel. The effects
      of zoledronic acid were determined by assessing cell number and rate of apoptosis
      by evaluating changes in nuclear morphology and using a fluorescence nick
      translation assay. Zoledronic acid caused a dose- and time-dependent decrease in
      cell number (P< 0.001) and a concomitant increase in tumour cell apoptosis (P<
      0.005). Short-term exposure to zoledronic acid was sufficient to cause a
      significant reduction in cell number and increase in apoptosis (P< 0.05). These
      effects could be prevented by incubation with geranyl geraniol, suggesting that
      zoledronic acid-induced apoptosis is mediated by inhibiting the mevalonate
      pathway. Treatment with zoledronic acid and clinically achievable concentrations
      of paclitaxel resulted in a 4-5-fold increase in tumour cell apoptosis (P< 0.02).
      Isobologram analysis revealed synergistic effects on tumour cell number and
      apoptosis when zoledronic acid and paclitaxel were combined. Short-term treatment
      with zoledronic acid, which closely resembles the clinical setting, has a clear
      anti-tumour effect on breast cancer cells. Importantly, the commonly used anti
      neoplastic agent, paclitaxel, potentiates the anti-tumour effects of zoledronic
      acid. These data suggest that, in addition to inhibiting bone resorption,
      zoledronic acid has a direct anti-tumour activity on breast cancer cells in
      vitro.

PMID- 11308266
TI  - Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal
      muscles from mice undergoing cancer cachexia.
AB  - A prominent feature of several type of cancer is cachexia. This syndrome causes a
      marked loss of lean body mass and muscle wasting, and appears to be mediated by
      cytokines and tumour products. There are several proteases and proteolytic
      pathways that could be responsible for the protein breakdown. In the present
      study, we investigated whether caspases are involved in the proteolytic process
      of skeletal muscle catabolism observed in a murine model of cancer cachexia
      (MAC16), in comparison with a related tumour (MAC13), which does not induce
      cachexia. Using specific peptide substrates, there was an increase of 54% in the
      proteolytic activity of caspase-1, 84% of caspase-8, 98% of caspase-3 151% to
      caspase-6 and 177% of caspase-9, in the gastrocnemius muscle of animals bearing
      the MAC16 tumour (up to 25% weight loss), in relation to muscle from animals
      bearing the MAC13 tumour (1-5% weight loss). The dual pattern of 89 kDa and 25
      kDa fragmentation of poly (ADP-ribose) polymerase (PARP) occurred in the muscle
      samples from animals bearing the MAC16 tumour and with a high amount of caspase
      like activity. Cytochrome c was present in the cytosolic fractions of
      gastrocnemius muscles from both groups of animals, suggesting that cytochrome c
      release from mitochondria may be involved in caspase activation. There was no
      evidence for DNA fragmentation into a nucleosomal ladder typical of apoptosis in
      the muscles of either group of mice. This data supports a role for caspases in
      the catabolic events in muscle involved in the cancer cachexia syndrome.

PMID- 11308267
TI  - Introduction. Improving the standard of care in the management of cancer-related
      anaemia: focus on darbepoetin alfa, a novel erythropoiesis-stimulating protein.

PMID- 11308268
TI  - Development and characterization of novel erythropoiesis stimulating protein
      (NESP).
AB  - Studies on human erythropoietin (EPO) demonstrated that there is a direct
      relationship between the sialic acid-containing carbohydrate content of the
      molecule and its serum half-life and in vivo biological activity, but an inverse
      relationship with its receptor-binding affinity. These observations led to the
      hypothesis that increasing the carbohydrate content, beyond that found naturally,
      would lead to a molecule with enhanced biological activity. Hyperglycosylated
      recombinant human EPO (rHuEPO) analogues were developed to test this hypothesis.
      Darbepoetin alfa (novel erythropoiesis stimulating protein, NESP, ARANESP, Amgen
      Inc, Thousand Oaks, CA), which was engineered to contain 5 N-linked carbohydrate
      chains (two more than rHuEPO), has been evaluated in preclinical animal studies.
      Due to its increased sialic acid-containing carbohydrate content, NESP is
      biochemically distinct from rHuEPO, having an increased molecular weight and
      greater negative charge. Compared with rHuEPO, it has an approximate 3-fold
      longer serum half-life, greater in vivo potency, and can be administered less
      frequently to obtain the same biological response. NESP is currently being
      evaluated in human clinical trials for treatment of anaemia and reduction in its
      incidence.

PMID- 11308269
TI  - Pharmacokinetics of novel erythropoiesis stimulating protein (NESP) in cancer
      patients: preliminary report.
AB  - Anaemia is a common occurrence in patients with cancer, and currently can be
      treated in several ways. Novel erythropoiesis stimulating protein (NESP,
      darbepoetin alfa) was created using site-directed mutagenesis to have 8 more
      sialic acid side chains than recombinant human erythropoietin (rHuEPO). The
      additional sialic acid content has resulted in an approximately 3-fold greater
      half-life relative to rHuEPO in patients with chronic renal failure. This study
      evaluates the pharmacokinetic profile of NESP in patients receiving multiple
      cycles of chemotherapy. Anaemic patients (haemoglobin < or = 11.0 g dl(-1)) who
      had non-myeloid malignancies received NESP weekly (2.25 mcg kg(-1) wk(-1)) under
      the supervision of a physician, starting on day 1 of chemotherapy for 3
      chemotherapy cycles given at 3-week intervals. Blood samples were collected
      during chemotherapy cycles 1 and 3 for pharmacokinetic analysis. All patients
      were followed for 4 weeks after treatment. NESP was well tolerated by all
      patients. After a single dose during chemotherapy cycle 1, pharmacokinetic
      parameters (mean (SD), n) for the first 15 patients were: T(max)86.1 (22.8) h (n
      = 14); C(max)9.0 (5.1) ng ml(-1)(n = 14); t(1/2,z)32.6 (11.8) h (n = 7); CL/F 3.7
      (1.0) ml h(-1) kg(-1)(n = 7). The subjects for whom all parameters could be
      calculated may represent a sub-group of the entire population. Similar results
      were obtained in cycle 3. In addition, haemoglobin response data suggests that,
      in this patient population, dosing less frequently than the 3 times weekly doses
      used for rHuEPO may be possible while improving anaemia.

PMID- 11308270
TI  - A dose-finding and safety study of novel erythropoiesis stimulating protein
      (NESP) for the treatment of anaemia in patients receiving multicycle
      chemotherapy.
AB  - Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which
      stimulates erythropoiesis by the same mechanism as recombinant human
      erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in
      patients with chronic renal failure. NESP is biochemically distinct from rHuEPO,
      due to its increased sialic acid content. NESP has an approximately 3-fold
      greater half-life. rHuEPO has been shown to be safe and effective for the
      treatment of chemotherapy-induced anaemia. This study assessed the safety and
      efficacy of NESP administered once per week, under the supervision of a
      physician, to patients with solid tumours who were receiving multicycle
      chemotherapy for up to 12 weeks. Three dose cohorts are presented in this
      sequential, unblinded and dose-escalating study. Thirteen to 59 patients received
      NESP (0.5, 1.5 or 2.25 mcg kg(-1)wk(-1)) in each cohort. Patients were monitored
      for adverse events, including antibody formation to NESP and for effects on
      haemoglobin. NESP appeared to be well tolerated. Adverse events were similar
      across all cohorts and were consistent with the population being studied. No
      antibody formation was detected over the 16-week study period and follow-up. A
      dose-response relationship was evident for NESP and multiple measures of
      efficacy, including proportion of patients responding to NESP and the mean change
      in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg(
      1)wk(-1)cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73
      and 2.15 g dl(-1)respectively). Controlled studies of this agent at higher doses
      and less frequent schedules of administration are ongoing.

PMID- 11308273
TI  - Editorial.

PMID- 11308271
TI  - Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of
      chronic disease associated with cancer.
AB  - Anaemia is a common haematologic disorder in patients with cancer and has a
      multifactorial aetiology, including the effects of the malignancy itself and
      residual effects from previous therapy. Novel erythropoiesis stimulating protein
      (NESP, darbepoetin alfa), a protein with additional sialic acid compared with
      erythropoietin (EPO), stimulates erythropoiesis by the same mechanism as
      recombinant human erythropoietin (rHuEPO) but it is biochemically distinct. NESP,
      with its approximately 3-fold greater serum half-life, can maintain haemoglobin
      levels as effectively as rHuEPO in anaemic patients with chronic renal failure
      and do so with less frequent dosing. We investigated the ability of NESP to
      safely increase haemoglobin levels of anaemic patients with non-myeloid
      malignancies not receiving chemotherapy. NESP was administered under the
      supervision of a physician at doses of 0.5, 1.0, 2.25 or 4.5 mcg kg(-1)wk(-1)for
      a maximum of 12 weeks. This report includes 89 patients completing the study by
      November 2000. NESP was well tolerated, with no reported dose-limiting toxicities
      or treatment-related severe adverse events. Increasing doses of NESP corresponded
      with increased efficacy. The percentage (95% confidence interval) of patients
      responding ranged from 61% (42%, 77%) in the 1.0 mcg kg(-1)wk(-1)group to 83%
      (65%, 94%) in the 4.5 mcg kg(-1)wk(-1)group.

PMID- 11308274
TI  - The scientific development of maxillofacial surgery in the 20th century and an
      outlook into the future.
AB  - Maxillofacial surgery is a relatively young speciality of medicine and it was not
      established as an organized specialty until the second half of the 20th century.
      At first it was supported by general surgeons with particular interest in this
      field, and also by inspired, extremely talented dentists. During the past few
      years modern techniques have brought decisive progress also in maxillofacial
      surgery, leading to rapid further development of diagnostic and therapeutic
      possibilities. The development of our specialty in the past century is discussed
      on the four main points of our scope, traumatology, orthognathic, cleft and
      tumour surgery.Considering the future prospects of our specialty one should
      realize that in the near future maxillofacial surgery will also be influenced by
      further medical-technical progress in the field of micro-robots, by percutaneous
      endoscopic techniques and by minimal invasive or laser surgery.Basic research
      will also cause a more profound change in our specialty, especially in the field
      of tumour therapy. Molecular biological research shows some good signs, which
      could already be transmitted to the prevention, diagnosis and also the therapy of
      tumours. In the field of tissue transplantation it is no longer utopia that
      autogenous tissue sampling can be almost completely be avoided. By further
      developing 'tissue engineering' it will be possible to cultivate bones as well as
      soft tissue with the aid of gene technology and transplant them into the face
      using relevant carrier substances. Altogether, the complexity of maxillofacial
      surgery in the coming century will increase, necessitating the best and widely
      trained maxillofacial surgeons for successful accomplishment. Copyright 2001
      European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308272
TI  - Anaemia and its functional consequences in cancer patients: current challenges in
      management and prospects for improving therapy.
AB  - Anaemia is a common occurrence in patients with cancer and contributes to the
      clinical symptomatology and reduced quality of life (QOL) seen in cancer
      patients. Many aspects of reduced QOL, including fatigue, are known to be
      associated with suboptimally low levels of haemoglobin. Even mild-to-moderate
      anaemia adversely affects patient-reported QOL parameters. Red blood cell
      transfusions are associated with many real and perceived risks, inconveniences,
      costs, and only temporary benefits. Recombinant human erythropoietin (rHuEPO) is
      an effective therapy to increase haemoglobin values in over half of anaemic
      cancer patients receiving concurrent chemotherapy. These increased haemoglobin
      values are closely correlated with improvements in QOL. Despite these objectively
      defined benefits, less than 50% of anaemic patients undergoing cytotoxic
      chemotherapy receive rHuEPO, in contrast to patients with chronic renal failure
      on dialysis, where anaemia is universally and aggressively treated to more
      optimal haemoglobin values. However, there are several barriers that may limit
      more widespread use of rHuEPO. These include inconvenience associated with
      frequent dosing; failure of a large proportion (40 to 50%) of patients to
      respond; relatively slow time to response; absence of reliable early indicators
      of response; and current lack of rigorous pharmacoeconomic data demonstrating
      cost-effectiveness. Darbepoetin alfa is a novel erythropoiesis stimulating
      protein (NESP) that is biochemically distinct from rHuEPO, and which has been
      proven to stimulate red blood cell production. The molecule has a 3-fold longer
      half-life and increased biological activity that will allow less frequent dosing,
      facilitating improved management of the anaemia of cancer. With this new option
      for therapy, further avenues of investigation should lead to renewed interest in
      the clinical benefits of optimal haemoglobin levels for patients with cancer.

PMID- 11308275
TI  - New Zealand Maori family with the pro250arg fibroblast growth factor receptor 3
      mutation associated with craniosynostosis.
AB  - Background: A large New Zealand Maori family has non-syndromic coronal
      craniosynostosis, which is inherited as an autosomal dominant mutation with
      variable expression. The aim of the study is to determine whether the family has
      the pro250 arg mutation in the gene for fibroblast growth factor receptor 3
      (FGFR3), a mutation found in patients with various types of craniosynostosis.
      Patients: Fourteen members of a New Zealand Maori family were evaluated, of whom
      five have coronal synostosis. A family pedigree tracing six generations was
      recorded. Methods: Blood samples were drawn for genomic DNA analysis from 14
      family members. Polymerase chain reaction, restriction-enzyme digestion and DNA
      sequencing was performed to identify the pro250arg mutation in FGFR3. Results:
      Seven family members were heterozygous for the pro250arg mutation in FGFR3. The
      mutation showed autosomal dominance with reduced penetrance and variable
      expressivity. Conclusion: Our data and those of other investigators suggest that
      we should begin integrating molecular diagnosis with phenotypic diagnosis of
      craniosynostoses. Copyright 2001 European Association for Cranio-Maxillofacial
      Surgery. 

PMID- 11308276
TI  - Standardized evaluation and documentation of findings in patients with
      craniosynostosis.
AB  - Surgical correction of craniosynostosis is usually performed according to
      standard procedures. However, a standard for clinical examination and report of
      findings for patients with craniosynostosis does not exist as yet. To compare
      findings from different hospitals, a documentation system was developed by a
      national craniosynostosis group. This system comprises a two-page document,
      clinical photographs, radiographs, CT scans, anthropometric measurements and
      molecular genetic findings. Data from craniosynostosis patients collected from
      participating hospitals are stored in a database, which facilitates online
      access.The documentation system was developed in cooperation with the group
      during 3 years since 1996. It was evaluated as being practicable and reliable and
      enables a comparability of findings reported in different hospitals. Molecular
      genetic analysis was found to support the investigation of patients with
      craniosynostosis and should therefore be integrated in the clinical evaluation.
      Copyright 2001 European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308277
TI  - Surgical correction of scaphocephaly: experiences with a new procedure and follow
      up investigations.
AB  - Introduction: Simple resection of the sagittal suture and the use of alloplastic
      material or extensive skull resections have long been proven to be unsatisfactory
      in the treatment of sagittal synostosis. In contrast to these experiences, the
      immediate correction of skull shape seems to yield the best results without
      significant morbidity. Patients: Thirty-six scaphocephalic infants with an
      average age of 6.5 (3.5-14) months underwent operation by our craniofacial team
      since 1994. Methods: Wide resection of the sagittal suture was used in
      combination with a bone-strip resection along the coronal and lambdoid sutures.
      Occasionally partial resection and reshaping of the frontal or occipital bone was
      necessary to correct an extremely bulging skull. The cranial growth and shape was
      monitored by anthropometric skull measurements in the last 20 patients. Results:
      Except in two cases, in which the dura mater was minimally injured
      intraoperatively, no complications occurred in any patient. Craniofacial oedema
      always occurred but disappeared after 72 h. The immediate correction of the skull
      shape was successful in all cases and was completed within 6 months
      postoperatively. There was no iatrogenic bone defect one year after surgery.
      Postoperative skull shape and growth was normal. Conclusion: These procedures
      seem to be effective in the treatment of scaphocephalus. Further normalization of
      skull shape is achieved by unrestricted postoperative brain growth. Copyright
      2001 European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308278
TI  - Repair of bilateral clefts of lip, alveolus and palate Part 1: A refined method
      for the lip-adhesion in bilateral cleft lip and palate patients.
AB  - The protruding premaxilla represents the most severe problem in the surgical
      closure of a bilateral cleft lip, alveolus and palate (BCLP). In principle there
      are two methods to overcome this obstacle: (1) preliminary lip adhesion and (2)
      presurgical repositioning with intraoral devices. According to the various
      degrees of premaxillary protrusion, sometimes adhesion alone is sufficient, if
      the surgical technique is unlikely to break down. In this paper a refined
      adhesion method is presented, withstanding traction to the wound margins and
      concomitantly enables lip and nose repairs in a single second operation. For
      patients with severe premaxillary protrusion, presurgical use of a Latham
      appliance achieves conditions for safe lip adhesion as above. Both treatment
      methods are outlined. Copyright 2001 European Association for Cranio
      Maxillofacial Surgery. 

PMID- 11308279
TI  - Repair of bilateral clefts of lip, alveolus and palate Part 2: Concomitant lip
      closure and columella lengthening after lip adhesion.
AB  - Lip repair and synchronous columella lengthening in bilateral clefts of the lip,
      alveolus and palate following lip adhesion according to the method outlined in
      Part 1 is described in this part of the paper. Together with lip and nose repair
      the gingivo-periosteoplasty can also be performed when the alveolar process is
      perfectly aligned and the greater and lesser segments abutt onto each other.
      Copyright 2001 European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308280
TI  - Repair of bilateral cleft lip, alveolus and palate Part 3: Follow-up criteria and
      late results.
AB  - The last part of this series outlines closure of the hard palate with various
      modifications depending on the remaining width of the cleft. Additionally the
      necessity and parameters of follow-up documentation are emphasized and detailed.
      For the two patients shown in Parts 1 and 2, the corresponding data are given.
      Accumulated facial growth curves of all the other patients treated the same way
      are also given. The main results are: (A) lip and nose can be reconstructed much
      more easily after repositioning of the premaxilla and (B) the reported anterior
      growth delay following use of the Latham appliance could not be confirmed during
      the ongoing follow-up. Copyright 2001 European Association for Cranio
      Maxillofacial Surgery. 

PMID- 11308281
TI  - Experimental microsurgery of salivary ducts in dogs.
AB  - The results achieved by experimental microsurgical suturing of salivary ducts in
      dogs are presented. Nine partial lesions and one complete transection of the
      ducts were made on parotid and submandibular ducts. Four to seven interrupted
      microsutures were used for each lesion. The operations were successful in seven
      out of 10 cases, as observed by sialography. Histologically, granulation tissue
      compressing the ducts was observed after suturing the lesions. Four venous graft
      transplantations were performed and none were successful. After venous graft
      transplantation, the transplant was not apparent histologically, raising doubt as
      to the potential success of this technique. The use of stenting is discussed
      based on a summary of the published literature. Those reports indicate that long
      term stenting can benefit the outcome of salivary duct repair. The use of dogs as
      a model for experimental salivary duct operations has been shown to be valuable
      in assessing various surgical techniques. Copyright 2001 European Association for
      Cranio-Maxillofacial Surgery. 

PMID- 11308282
TI  - Analysis of the osseous/metal interface of drill free screws and self-tapping
      screws.
AB  - Aim: A comparison of metal/osseous interface and bone remodelling after insertion
      of different types of titanium bone screws in vivo. Material: Samples of five of
      each of the following bone screw types were inserted into the anterior wall of
      the frontal sinus of five Gottingen minipigs: self-tapping micro- (1.5 mm) and
      miniscrews (2.0 mm) or drill free micro- (1.5 mm) and miniscrews (2.0 mm) (Martin
      Medizintechnik, Tuttlingen, Germany). Screw length was 7 mm. Methods: Sequential
      intraperitoneal injections of fluorochromes were performed between the second and
      ninth postoperative week. After 6 months the pigs were sacrificed, the screw-bone
      blocks resected, and microradiographic, histological and fluorescence
      microscopical examinations were carried out. Results: Using drill free screws,
      mean screw/bone contact was 88.4% (miniscrews), or 93.8% (microscrews). With self
      tapping miniscrews it was 54.9%, but in microscrews 81%; the differences were
      statistically significant (t -test: p<0.05). By fluorescence microscopy, the
      amount of bone remodelling (ratio of residual vs. newly formed bone) was
      measured. Significantly more of the residual bone was found in the region of the
      screw threads using drill free screws (miniscrews: mean 71.8%, microscrews: mean
      67.9%) than in the region of screw threads with self-tapping screws (miniscrews:
      mean 33.1%, microscrews: mean 42.4%). Conclusion: The present data support the
      view that screw/bone contact with drill free screws was superior to that of self
      tapping screws; the greater amount of original bone in the threads of drill free
      screws demonstrated that the insertion of drill free screws did not cause harm to
      the surrounding bone. Both results are important for osteosynthesis in regions
      where thin cortical bone is present, such as the central midface. Copyright 2001
      European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308283
TI  - Long-term results following reconstruction of craniofacial defects with titanium
      micro-mesh systems.
AB  - Introduction: Reconstruction of craniofacial defects can be carried out with
      autogenous tissue (calvarium, rib, iliac crest), allogeneic implants (AAA-bone,
      lyophilized cartilage) or alloplastic material (methacrylate, hydroxyapatite,
      titanium implants and mesh systems). Selection of the implant material used for
      reconstruction is still controversial. Material and Methods: At the Department of
      Oral and Maxillofacial Surgery, Kantonsspital Luzern, 20 patients with defects in
      the craniofacial and/or orbito-ethmoidal region have been treated using titanium
      micro-mesh between 1991 and 1998. Two different mesh systems, micro-titanium
      augmentation mesh and dynamic mesh, have been used for bony reconstruction in non
      load-bearing areas. The defects were caused by acute trauma, osteomyelitis of the
      frontal bone and previous operations. The titanium micro-mesh was used with the
      following indications: (1) immediate reconstruction in the primary treatment of
      comminuted fractures with bone loss in non load-bearing areas, (2) treatment of
      contour irregularities (possibly in combination with bone or cartilage grafts).
      All patients were followed up clinically and radiographically at quarterly
      intervals for a year. Results: No wound infections, exposures or loss of the mesh
      have been observed. Long-term stability of the reconstructions was excellent.
      When walls of the paranasal sinuses were reconstructed complete repneumatisation
      took place. Conclusions: Advantages of this reconstructive technique are: (1)
      universal applicability (craniofacial, orbital, sinus defects, comminuted
      fractures); (2) stable 3-D reconstruction of complex anatomic structures were
      easily performed; (3) immediate availability with no donor site morbidity as bone
      or cartilage grafts were not necessary; (4) combination with bone or cartilage
      grafts is possible; and (5) very low susceptibility to infection. Copyright 2001
      European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308284
TI  - Effectiveness of a new perforated 0.15 mm poly-p-dioxanon-foil versus titanium
      dynamic mesh in reconstruction of the orbital floor.
AB  - Introduction: In recent years a new perforated PDS (poly-p-dioxanon) foil (0.15
      mm) has become available and has not yet been proven to be successful in
      reconstruction of the orbital floor after blow-out-fractures in randomized
      studies. The main aim of this clinical trial is to compare this new PDS foil with
      titanium dynamic mesh (0.3 mm) (TD), which is well established in reconstruction
      of the orbital floor. Patients and Methods: In a prospective multicentre
      randomized trial, conducted between 1997 and 1998, out of 42 patients with
      fractures of the orbital floor, 28 patients needing material for reconstruction
      were randomized to receive either PDS foil or TD. In a comprehensive preoperative
      and postoperative protocol patients were monitored by the surgeon, radiologist
      and ophthalmologist with a postoperative follow-up of least 6 months. Results:
      Maximum defects of the orbital floor were comparable in both groups (PDS group:
      13.3 mm, TD group: 13.9 mm). In both groups the surgical procedure was well
      tolerated, and functional and cosmetic results were evaluated as satisfactory by
      all patients. Ophthalmological evaluation, performed up to 6 months
      postoperatively, revealed double vision or vertical strabismus in nine patients
      (five PDS group, four titanium group). This was not confirmed subjectively in
      each single patient. Also ex- or enophthalmos, registered in seven patients of
      the PDS and four of the TD group (mainly +/-1 mm) were not considered as relevant
      by the patients. Conclusion: The new 0.15 mm perforated PDS foil was comparable
      to 0.3 mm titanium mesh concerning functional and cosmetic outcome. Obviously,
      persisting ophthalmometric disorders were compensated very well in both groups.
      PDS foil is felt to be the preferred material since it is bioresorbable and more
      convenient to handle. Copyright 2001 European Association for Cranio
      Maxillofacial Surgery. 

PMID- 11308285
TI  - Pumping injection of sodium hyaluronate for patients with non-reducing disc
      displacement of the temporomandibular joint: two year follow-up.
AB  - Objectives: The purpose of the present study was to examine the long-term effect
      of pumping injection of sodium hyaluronate into the TMJ in patients with non
      reducing disc displacement. Patients: Sixty patients with non-reducing disc
      displacement underwent pumping injection of sodium hyaluronate (pumping group).
      Seventy-six patients with non-reducing disc displacements were observed without
      any active treatment (observation group). Study design: In both patient groups
      clinical signs and symptoms were observed periodically for 2 years. Variables
      such as age, range of maximum mouth opening, angle of posterior slope of the
      articular eminence and degenerative bony changes of the condyle at the initial
      visit were also examined. Cox hazards analysis was applied to examine the
      clinical outcome for such variables in addition to the results of pumping
      injection of sodium hyaluronate. Results: Pumping injection of sodium hyaluronate
      seemed to have a favourable effect when compared with the control group
      (untreated) (p=0.0002). However, the four background variables mentioned could
      not be explained as predictors of outcome. Conclusion: Pumping injection of
      sodium hyaluronate seems to be effective for non-reducing disc displacement of
      the temporomandibular joint. Copyright 2001 European Association for Cranio
      Maxillofacial Surgery. 

PMID- 11308286
TI  - The fate of developing teeth in mandibular lengthening by distraction: an
      experimental study.
AB  - Purpose: The purpose of this study was to observe developing teeth in a
      lengthened mandible after distraction. Material: Ten mongrel dogs with deciduous
      dentitions were used. Methods: A corticotomy was carefully made around a tooth
      bud and the external distractor (Orthofix M-100((R))) was connected. After a 5
      day latent period, distraction was started at a rate of 0.75 mm per day for 10
      consecutive days. Then, the lower jaw was stabilized by an external fixation to
      allow ossification. While the operation was performed on the left side
      (Distraction group), the contralateral side was studied for comparison (Control).
      In addition, a corticotomy, artificial fracture and external fixation were
      carried out to confirm the influence of the operation (Fracture group). Then
      macroscopic, radiographic and histological evaluations were carried out. Results:
      In the Distraction group, the space between the wall of the dental follicle and
      the crown expanded as distraction began. The end of the calcified root became
      wider and irregular during the distraction period, and finally, the apex closed.
      In the Fracture group, the teeth erupted although slight alterations of the root
      shape were observed in association with the operation period. Conclusion: The
      root became irregular, but the teeth erupted within the distraction area.
      Copyright 2001 European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308287
TI  - Bone loading pattern around implants in average and atrophic edentulous maxillae:
      a finite-element analysis.
AB  - Introduction: Oral implants placed in the maxilla, especially the posterior
      region, have a lower success rate than those placed in the mandible. Poor bone
      quantity and quality have been suggested as a reason for this differential
      success rate. Objective: The purpose of this study was, therefore, to evaluate
      stress and strain distributions around loaded implants in the normal and atrophic
      maxilla by finite-element (FE) analyses. Material: FE models of a solitary
      implant were generated to determine stresses and strains in the bone adjacent to
      the implant surface under loading conditions. Study design: Different bony
      situations and implant lengths were used in a FE model. Static loads were applied
      axially and the resulting stresses and strains calculated. Results: Bone quality
      and quantity play a major role in decreasing bone strains adjacent to the implant
      surface under loading. It was found that stresses were more homogeneously
      distributed when more spongy bone was present. Decreased bone height was found to
      have less pronounced effects on strain and stress alterations than poor bone
      quality. Atrophic bony dimensions in combination with poor bone quality were
      associated with surface strains exceeding physiological levels (>6000
      microstrains). Conclusion: Our investigation indicates that supraphysiological
      bone strains adjacent to the implant surface should be expected under mechanical
      loading in the atrophic maxilla. Copyright 2001 European Association for Cranio
      Maxillofacial Surgery. 

PMID- 11308288
TI  - Malformation of the vomer in submucous cleft palate.
AB  - Background: Several criteria are described in the literature to diagnose a
      submucous cleft palate. Commonly the differences in the extent of the submucous
      cleft will not be as overt as in open clefts. Nevertheless, complete submucous
      cleft palate may cause imperfect palato-pharyngeal closure so that the affected
      person needs to undergo speech training and surgical treatment. Patients: We
      investigated 30 patients who underwent palatal repair to correct this disorder.
      They were evaluated according to the Koch's documentation system. Results: In all
      patients an additional malformation of the inner nose was found: The vomer was
      not fused with the palatal shelves. There were with different degrees of severity
      of this malformation and they were not necessarily correlated with the extent of
      the palatal cleft. Conclusion: In our opinion, this malformation of the vomer
      should be seen as a typical symptom of classical submucous cleft palate.
      Discussion is needed on how the vomerine malformation should be incorporated into
      the surgical procedure. Since we know from septal surgery that a basal septal
      perforation will lead to disturbances of nasal breathing. Copyright 2001 European
      Association for Cranio-Maxillofacial Surgery. 

PMID- 11308289
TI  - Purulent pansinusitis, orbital cellulitis and rhinogenic intracranial
      complications.
AB  - Objectives: Acute pansinusitis is rarely seen in the maxillofacial surgery field,
      but often occurs in combination with orbital and intracranial involvement.
      Clinically this entity is of great importance, since it represents a severe
      disease with possibly disastrous consequences. Patients: Aetiology, diagnosis and
      therapy of acute pansinusitis and its complications were analysed in 36 patients
      treated surgically from 1987 to 1996. Results: Eighteen patients were aged
      between 3 and 21-years-old. Only eight suffered from pure pansinusitis, and three
      of an isolated purulent orbital infection. Of these 25 patients 20 had (pan
      )sinusitis with orbital, three with intracranial, and two with both orbital and
      intracranial complications. Intracranial involvement included meningitis, empyema
      and brain abscess. Aetiology was rhinogenic in 26, odontogenic in six patients,
      and traumatic in two cases. Radiological work-up included conventional
      radiographs and CT in most cases, MRI was only used with special indications.
      Microbiological examination detected single or multiple species of micro
      organisms with equal frequency. If multiple species were found, infection was
      mostly aerobic/anaerobic in combination. Conclusion: These purulent processes,
      frequently seen in young patients, require immediate surgical intervention and
      drainage with elimination of the cause of the disease if possible. Cooperation
      with other specialities is essential depending on the spread of the disease. In
      spite of the threatening acute symptoms, severe courses of disease or permanent
      defects should be avoidable. Copyright 2001 European Association for Cranio
      Maxillofacial Surgery. 

PMID- 11308290
TI  - Autologous blood transfusion in oral and maxillofacial surgery patients with the
      use of erythropoietin.
AB  - Background: Autologous blood transfusion presents few infectious or immunologic
      side effects. The aim of the present study was to determine the impact of
      autologous blood transfusion with or without recombinant human erythropoietin
      (rHuEPO) in patients who underwent elective maxillofacial operations. Material:
      Seventy eight consecutive patients (29 men and 49 women) underwent elective
      maxillofacial operations during the years 1990-95. Study design and Methods: The
      patients were randomly assigned to three groups: In group 1, 30 patients
      preoperatively underwent autologous blood predonation with intravenous injection
      of erythropoietin 600 IU/kg after each blood predonation and autologous blood
      transfusion intraoperatively; in group 2, 28 patients underwent the same
      procedure without erythropoietin and in group 3, 20 patients underwent homologous
      transfusion serving as control group. All patients received ferrous sulphate
      daily by mouth, preoperatively until one week postoperatively. Results: Group 1
      patients showed higher levels of haematocrit, haemoglobin and red blood cell
      count pre- and postoperatively than the group 2 patients. It was also shown that
      the use of rHuEPO contributed to an improvement of the blood parameters of the
      patients in the group 1 compared with those of the patients in groups 2 and 3.
      Copyright 2001 European Association for Cranio-Maxillofacial Surgery. 

PMID- 11308292
TI  - Raft membrane domains: from a liquid-ordered membrane phase to a site of pathogen
      attack.
AB  - While the existence of cholesterol/sphingolipid (raft) membrane domains in the
      plasma membrane is now supported by strong experimental evidence, the structure
      of these domains, their size, their dynamics, and their molecular composition
      remain to be understood. Raft domains are thought to represent a specific
      physical state of lipid bilayers, the liquid-ordered phase. Recent observations
      suggest that in the mammalian plasma membrane small raft domains in ordered lipid
      phases are in a dynamic equilibrium with a less ordered membrane environment.
      Rafts may be enlarged and/or stabilized by protein-mediated cross-linking of raft
      associated components. These changes of plasma membrane structure are perceived
      by the cells as signals, most likely an important element of immunoreceptor
      signalling. Pathogens abuse raft domains on the host cell plasma membrane as
      concentration devices, as signalling platforms and/or entry sites into the cell.
      Elucidation of these interactions requires a detailed understanding raft
      structure and dynamics.

PMID- 11308293
TI  - Fc(epsilon)RI as a paradigm for a lipid raft-dependent receptor in hematopoietic
      cells.
AB  - Lipid domains or rafts are currently embraced by immunologists as critical
      participants in receptor-mediated signaling events occurring at the plasma
      membrane. This view of membrane heterogeneity and its functional importance is
      supported by many years of different experimental approaches. We can now refine
      our investigations, moving beyond the simple models to ask more detailed
      questions about structural properties and mechanistic interactions. As
      highlighted for the IgE receptor (Fc(epsilon)RI), new information about initial
      engagement with src family kinases, cytoskeletal regulation, and coupling with
      downstream signaling is beginning to emerge.

PMID- 11308294
TI  - Floating the raft hypothesis: the roles of lipid rafts in B cell antigen receptor
      function.
AB  - The initiation of antibody responses to foreign antigens requires that B cells
      receive and integrate a variety of signals through an array of cell surface
      receptors including the B cell antigen receptor (BCR) as well as a number of
      essential coreceptors. Recent evidence indicates that cholesterol-rich plasma
      membrane microdomains, referred to here as lipid rafts, serve as platforms for
      BCR signaling and trafficking in B cells. The existence of rafts suggests a
      previously unappreciated level of organization at the B cell surface that may
      explain, at least in part, how BCR signaling is coordinated. Here the current
      evidence that lipid rafts play a key role in B cell responses is reviewed.

PMID- 11308295
TI  - Co-stimulation and counter-stimulation: lipid raft clustering controls TCR
      signaling and functional outcomes.
AB  - T cell receptor (TCR) antigen recognition induces the formation of a specialized
      'immunological synapse' at the T cell : antigen presenting cell (APC) junction.
      This junction is generated by the recruitment and exclusion of particular
      proteins from the contact area and is required for T cell activation. We and
      others have hypothesized that lipid raft/non-raft partitioning provides a
      molecular basis for protein sorting which organizes the TCR, co-stimulators,
      signal transducers and the actin cytoskeleton at the T cell : APC interface. Here
      we discuss the emerging paradigm that co-stimulators induce the directional
      transport and clustering of lipid rafts at the T cell : APC interface, thus
      generating platform(s) specialized for processive and sustained TCR signal
      transduction and T cell activation. We also discuss recent data implicating the
      involvement of 'counter-stimulators' and other negative regulators which prevent
      optimal raft clustering at the TCR contact site and, thus, facilitate T cell
      inactivation and tolerance induction.

PMID- 11308296
TI  - Changes in the T cell receptor macromolecular signaling complex and membrane
      microdomains during T cell development and activation.
AB  - Initiation and propagation of T cell receptor signaling pathways involves the
      mobilization and aggregation of a variety of signaling intermediates with the T
      cell receptor and associated molecules into specialized signaling complexes.
      Accumulating evidence suggests that differential regulation of the formation and
      composition of the T cell receptor macromolecular signaling complex may affect
      the different biological consequences of T cell activation. The regulatory
      mechanisms involved in the assembly of these complexes remains poorly understood,
      but in part is affected by the avidity of the T cell receptor ligand, co
      stimulatory signals, and by the differentiation state of the T cell.

PMID- 11308297
TI  - Membrane lipid microdomains and the role of PKCtheta in T cell activation.
AB  - Productive T cell activation depends on the assembly of a highly ordered and
      compartmentalized immunological synapse or supramolecular activation complex
      (SMAC). Reorganization of the actin cytoskeleton and clustering of specialized
      membrane microdomains, or lipid rafts, occur early following TCR/CD3 and
      costimulatory receptor ligation. Many key signaling molecules localize in lipid
      raft patches during T cell activation. Lipid raft reorganization is required for
      T cell activation, where it plays an apparently important role in stabilizing the
      T cell synapse. Here we review recent evidence supporting the role of lipid rafts
      in T cell activation. Particular emphasis is placed on the coupling of protein
      kinase C-theta(PKCtheta), which is selectively expressed in T cells and is known
      to function as an essential signal for T cell activation, and lipid rafts.

PMID- 11308298
TI  - Membrane raft microdomains in chemokine receptor function.
AB  - Cell chemotaxis requires the acquisition and maintenance of both spatial and
      functional asymmetry between initially equivalent cell parts. In leukocytes one
      becomes the leading edge and the other, the rear edge or uropod. The acquisition
      of this cell polarity is controlled by an array of chemoattractants, including
      those of the chemokine family. We propose that chemokine receptor activation in
      highly organized lipid raft domains is a major determinant for the correct
      localization of the signaling pathways leading to the cell asymmetries required
      for migration. The lateral organization imposed by membrane raft microdomains is
      discussed in the context of other chemokine receptor activities, such as its role
      as a human immunodeficiency virus (HIV) coreceptor.

PMID- 11308299
TI  - Some interesting properties of metals confined in time and nanometer space of
      different shapes.
AB  - The properties of a material depend on the type of motion its electrons can
      execute, which depends on the space available for them (i.e., on the degree of
      their spatial confinement). Thus, the properties of each material are
      characterized by a specific length scale, usually on the nanometer dimension. If
      the physical size of the material is reduced below this length scale, its
      properties change and become sensitive to its size and shape. In this Account we
      describe some of the observed new chemical, optical, and thermal properties of
      metallic nanocrystals when their size is confined to the nanometer length scale
      and their dynamical processes are observed on the femto- to picosecond time
      scale.

PMID- 11308300
TI  - Subpicosecond solvent dynamics in charge-transfer transitions: challenges and
      opportunities in resonance Raman spectroscopy.
AB  - Resonance Raman spectroscopy is an established tool for the determination of
      structure and dynamics in electronically excited states. In condensed-phase
      systems, Raman excitation profiles and electronic absorption spectra depend on
      changes in molecular geometry and solvation structure induced by electronic
      excitation. Recent studies of solvent isotope effects on resonance Raman
      intensities in charge-transfer excitations reveal solvent dynamics taking place
      on a subpicosecond time scale and vibrational mode-specific solute-solvent
      interactions. These discoveries present challenges to the current working
      theories for analysis of resonance Raman and absorption spectra.

PMID- 11308301
TI  - Theoretical perspectives on proton-coupled electron transfer reactions.
AB  - This Account presents a theoretical formulation for proton-coupled electron
      transfer reactions. The active electrons and transferring protons are treated
      quantum mechanically, and the free energy surfaces are obtained as functions of
      collective solvent coordinates corresponding to the proton and electron transfer
      reactions. Rate expressions have been derived in the relevant limits, and
      methodology for including the dynamical effects of the solvent and protein has
      been developed. This theoretical framework allows predictions of rates,
      mechanisms, and kinetic isotope effects for proton-coupled electron transfer
      reactions.

PMID- 11308302
TI  - Multiple isotope effects on the acyl group transfer reactions of amides and
      esters.
AB  - Acyl group transfer reactions, especially those to amides and esters, are
      important in biochemistry. Multiple kinetic isotope effects for the atoms at the
      reactive center of these molecules have provided the most detailed bonding
      picture of the transition state to date. These kinetic isotope effect studies are
      reviewed for several reactions of formamide, methyl benzoate, and methyl formate.
      In these cases all the evidence is consistent with a stepwise mechanism,
      involving tetrahedral intermediates. In the case of p-nitrophenyl acetate, the
      change to an excellent leaving group causes the tetrahedral intermediates to
      become kinetically unstable; the kinetic isotope effects are best fitted to a
      concerted mechanism.

PMID- 11308303
TI  - The quantum world of cold electron collisions.
AB  - Collisions between electrons and molecules at thermal energy play a key role in
      the chemistry and physics of plasmas, ranging from those in space to the
      chemically active plasmas used for thin film and microcircuit fabrication.
      However, until recently, data for electron-molecule interactions below a few
      hundred millielectronvolts impact energy (a few thousand kelvin) were very
      sparse. Our experiments, using a high-resolution synchrotron photoionization
      source of electrons, have opened up this low-energy field. We present recent
      results which reveal some of the striking quantum scattering events which take
      place as long-wavelength, low-energy electrons encounter molecules, choosing
      H(2), N(2), benzene, halobenzenes, methanol, ozone, and chlorine dioxide as
      examples.

PMID- 11308304
TI  - Substrate dehydrogenation by flavoproteins.
AB  - Enzymes with tightly bound FMN or FAD as cofactor catalyze the oxidation of a
      wide range of substrates. The chemical versatility of the isoalloxazine ring
      provides these enzymes with a range of potential mechanisms. Recent progress in
      elucidating the mechanisms of oxidation of organic substrates by flavoenzymes is
      described, focusing on the oxidation of alcohols, amino and hydroxy acids,
      amines, and nitroalkanes. With each family of enzymes, an attempt is made to
      integrate mechanistic, structural, and biomimetic data into a common catalytic
      mechanism.

PMID- 11308305
TI  - Homogeneous single-component betaine Ziegler-Natta catalysts derived from
      (butadiene)zirconocene precursors.
AB  - (Butadiene)zirconocene adds B(C(6)F(5))(3) at a terminal diene carbon atom to
      yield the zirconocene-(mu-hydrocarbyl)-borate betaine Cp(2)Zr[C(4)H(6)
      B(C(6)F(5))(3)] (4). The dipolar complex 4 contains a distorted pi-allyl moiety
      and features an additional stabilizing Zr-F-C(arene) coordination. Under kinetic
      control, an isomeric betaine system is formed, characterized by an internal
      Zr(+).CH(2)[B](-) ion-pair interaction, that rearranges to 4 upon heating. A
      great variety of ansa-metallocene(butadiene) complexes and related systems
      cleanly form analogous metallocene-(mu-conjugated diene)-borate betaines upon
      treatment with B(C(6)F(5))(3) and related Lewis acids. Most of these systems
      represent very active homogeneous single-component Ziegler-Natta catalysts for
      alpha-olefin polymerization and copolymerization. In addition, these betaine
      catalysts are ideally suited for carrying out mechanistic studies in active
      Ziegler-Natta catalyst systems. They allow for an experimental observation of the
      first alkene insertion step at the active single-component catalyst. This feature
      has been used for studying the mechanism of transfer of the stereochemical
      information from the bent metallocene backbone and for an experimental
      characterization of the energy profile of the alkene addition/alkene insertion
      reaction sequence in active homogeneous Ziegler-Natta systems. The neutral
      dipolar single-component catalysts (e.g., 4) produce a polyolefin-modified R'
      (CHR-CH(2))-C(4)H(6)-B(C(6)F(5))(3)(-) counterion at the end of the initiation
      period upon entering into the repetitive active catalytic cycle.

PMID- 11308306
TI  - Modular chemistry: secondary building units as a basis for the design of highly
      porous and robust metal-organic carboxylate frameworks.
AB  - Secondary building units (SBUs) are molecular complexes and cluster entities in
      which ligand coordination modes and metal coordination environments can be
      utilized in the transformation of these fragments into extended porous networks
      using polytopic linkers (1,4-benzenedicarboxylate, 1,3,5,7
      adamantanetetracarboxylate, etc.). Consideration of the geometric and chemical
      attributes of the SBUs and linkers leads to prediction of the framework topology,
      and in turn to the design and synthesis of a new class of porous materials with
      robust structures and high porosity.

PMID- 11308307
TI  - Biotechnology and the Journal of agricultural and food chemistry.

PMID- 11308308
TI  - Determination of tetracycline and streptomycin in mixed fungicide products by
      capillary zone electrophoresis.
AB  - A method of capillary zone electrophoresis (CZE) was used to determine
      tetracycline and streptomycin content in commercial agriculture products. The
      results indicated that this method was capable of analyzing the mixed fungicide
      in formulated products with instrument detection limit (IDL) of 0.50 microg/mL
      and a method detection limit (MDL) of 0.52 microg/mL for tetracycline, and IDL of
      1.00 microg/mL and MDL of 1.22 microg/mL for streptomycin. Precision expressed by
      relative standard deviation (RSD) ranged from 1.44 to 4.37% of tetracycline and
      1.00 to 4.20% of streptomycin. Recoveries were in the region of 98.2-102.5% for
      tetracycline and 95.3--103.0% for streptomycin. The low detection limit, the low
      RSD values, and the high percentage of recovery confirmed that the CZE technique
      is a sensitive and selective method. And the CZE method can analyze both
      tetracycline and streptomycin at the same time without complicated extraction and
      further derivative reaction.

PMID- 11308309
TI  - Development of an immunoassay (ELISA) for the quantification of thiram in
      lettuce.
AB  - Two competitive immunoassays, a laboratory assay based on microwell plates and a
      field test based on the use of polystyrene tubes, have been developed for the
      quantification of thiram in lettuces. Concerning the laboratory assay, the
      calibration curve for thiram had a linear range of 11 to 90 ng/mL and a detection
      limit of 5 ng/mL. Precision of the assay presented coefficient of variation
      values <9% and the recovery of thiram from lettuce averaged 89% across the range
      of the immunoassay method using 30 min extraction with water/acetone (50:50,
      v/v). The tube-based method was developed in order that an extract of lettuce,
      containing thiram at the MRL (8 ppm), would be found on the linear part of the
      standard curve. The calibration curve for thiram has a linear range of 100 to 800
      ng/mL (1.39 to 11.1 ppm in lettuce) and a detection limit of 40 ng/mL.

PMID- 11308310
TI  - Trimethylamine and total volatile basic nitrogen determination by flow
      injection/gas diffusion in Mediterranean hake (Merluccius merluccius).
AB  - The reliability of flow injection/gas diffusion (FIGD) methods to determine
      trimethylamine (TMA-N) and total volatile basic nitrogen (TVB-N) in hake was
      studied in order to find an alternative and accurate, simple, cheap, and rapid
      method for non-protein nitrogen determination. FIGD methods involved extracting
      volatile amines with 7.5% trichloroacetic acid, followed by the injection of the
      extracts into the FIGD manifold, previously adjusted for TMA-N or TVB-N
      determinations. Each determination took approximately 2 min. Reliability was
      satisfactory in linearity, precision, recovery, and sensitivity. There was good
      correlation (p < 0.001) between FIGD and the classic official methods, for both
      TMA-N and TVB-N determinations, and also between FIGD and the gas chromatographic
      procedure described for TMA-N. These results proved that FIGD methods are
      simpler, cheaper, and faster than current official procedures. To check the
      suitability of FIGD procedures over a wide range of analyte concentrations,
      changes of both TMA-N and TVB-N and the P ratio values throughout the ice storage
      of hake were monitored. The usefulness of each of these potential freshness
      indicators for hake is discussed.

PMID- 11308311
TI  - Specific screening for color precursors and colorants in beet and cane sugar
      liquors in relation to model colorants using spectrofluorometry evaluated by HPLC
      and multiway data analysis.
AB  - A comparison was made of the fluorophores in beet thick juice and cane final
      evaporator syrup, which are comparable in the production of cane and beet sugar;
      that is, both represent the final stage of syrup concentration prior to
      crystallization of sugar. To further elucidate the nature of the color components
      in cane and beet syrup, a series of model colorants was also prepared, consisting
      of mildly alkaline-degraded fructose and glucose and two Maillard type colorants,
      glucose--glycine and glucose--lysine. Fluorescence excitation--emission
      landscapes resolved into individual fluorescent components with PARAFAC modeling
      were used as a screening method for colorants, and the method was validated with
      size exclusion chromatography using a diode array UV--vis detector. Fluorophores
      from the model colorants were mainly located at visible wavelengths. An overall
      similarity in chromatograms and absorption spectra of the four model colorant
      samples indicated that the formation of darker color was the distinguishing
      characteristic, rather than different reaction products. The fluorophores
      obtained from the beet and cane syrups consisted of color precursor amino acids
      in the UV wavelength region. Tryptophan was found in both beet and cane syrups.
      Tyrosine as a fluorophore was resolved in only beet syrup, reflecting the higher
      levels of amino acids in beet processing. In the visible wavelength region, cane
      syrup colorant fluorophores were situated at higher wavelengths than those of
      beet syrup, indicating formation of darker colorants. A higher level of invert
      sugar in cane processing compared to beet processing was suggested as a possible
      explanation for the darker colorants.

PMID- 11308312
TI  - Rapid analysis of inositol phosphates.
AB  - Fast and simple analytical methods for the determination of inositol bis- to
      hexakisphosphates or only inositol hexakisphosphate in foods and feces are
      presented. The methods are both faster and simpler with regard to analytical
      detection and sample pretreatment as compared to previously reported methods. The
      samples are pretreated using extraction and centrifugal ultrafiltration and
      analyzed using high-performance ion chromatography (HPIC) with gradient or
      isocratic elution. The analytes are detected using ultraviolet detection after
      postcolumn reaction. The methods are efficient, highly selective, and appropriate
      for analyzing inositol phosphates in food and feces samples. The between- and
      within-day variances were generally below 8 and 5% (relative standard deviation),
      respectively, for the presented HPIC method with gradient elution.

PMID- 11308313
TI  - Echinacea standardization: analytical methods for phenolic compounds and typical
      levels in medicinal species.
AB  - A proposed standard extraction and HPLC analysis method has been used to measure
      typical levels of various phenolic compounds in the medicinally used Echinacea
      species. Chicoric acid was the main phenolic in E. purpurea roots (mean 2.27%
      summer, 1.68% autumn) and tops (2.02% summer, 0.52% autumn), and echinacoside was
      the main phenolic in E. angustifolia (1.04%) and E. pallida roots (0.34%).
      Caftaric acid was the other main phenolic compound in E. purpurea roots (0.40%
      summer, 0.35% autumn) and tops (0.82% summer, 0.18% autumn), and cynarin was a
      characteristic component of E. angustifolia roots (0.12%). Enzymatic browning
      during extraction could reduce the measured levels of phenolic compounds by >50%.
      Colorimetric analyses for total phenolics correlated well with the HPLC results
      for E. purpurea and E. angustifolia, but the colorimetric method gave higher
      values.

PMID- 11308314
TI  - Monoclonal enzyme immunoassay for the analysis of carbaryl in fruits and
      vegetables without sample cleanup.
AB  - The N-methylcarbamate pesticide carbaryl is one of the most important
      insecticides used worldwide. In the present work, the validation of a monoclonal
      antibody-based enzyme immunoassay (ELISA) for the determination of this compound
      in fruits and vegetables is described. The immunoassay is a competitive
      heterologous ELISA in the antibody-coated format, with an I(50) value for
      standards in buffer of 101.0 +/- 26.9 ng/L and with a dynamic range between 31.6
      and 364.0 ng/L. For recovery studies, peppers, cucumbers, strawberries, tomatoes,
      potatoes, oranges, and apples were spiked with carbaryl at 10, 50, and 200 ppb.
      After liquid extraction, analyses were performed by ELISA on both extracts
      purified on solid-phase extraction (SPE) columns and crude, nonpurified extracts.
      Depending on the crop and the fortification level, recoveries in the 59.0--120.0%
      range were obtained for purified samples and in the 70.0--137.7% range for crude
      extracts. The carbaryl immunoassay performance was further validated with respect
      to high-performance liquid chromatography (HPLC) with postcolumn derivatization
      and fluorescence detection (EPA Method 531.1). Samples were spiked with carbaryl
      at several concentrations and analyzed as blind samples by ELISA and HPLC after
      SPE cleanup. The correlation between methods was excellent (y = 1.04x + 0.71,
      r(2) = 0.992, n = 33), with HPLC being more precise than ELISA (mean coefficients
      of variation of 5.2 and 12.0%, respectively). The immunoassay was then applied to
      the analysis of nonpurified extracts of the same samples. Results also compared
      very well with those obtained by HPLC on purified samples (y = 1.28x - 0.59, r(2)
      = 0.987, n = 33) while maintaining similar precision. Therefore, the developed
      immunoassay is a suitable method for the quantitative and reliable determination
      of carbaryl in fruits and vegetables even without sample cleanup, which saves
      time and money and considerably increases sample throughput.

PMID- 11308315
TI  - Validation of a monoclonal enzyme immunoassay for the determination of carbofuran
      in fruits and vegetables.
AB  - The N-methylcarbamate pesticide carbofuran is a very important insecticide used
      worldwide. In the present work, the validation of a monoclonal antibody-based
      enzyme immunoassay (ELISA) to determine this compound in fruits and vegetables is
      described. The immunoassay is a competitive heterologous ELISA in the antibody
      coated format, with an I(50) value for standards in buffer of 740 ng/L and with a
      dynamic range between 200 and 3100 ng/L. For recovery studies, peppers,
      cucumbers, strawberries, tomatoes, potatoes, oranges, and apples were spiked with
      carbofuran at 10, 50, and 200 ppb. After liquid extraction, analyses were
      performed by ELISA on extracts purified on solid-phase extraction (SPE) columns
      and crude, nonpurified extracts. Depending on the crop, mean recoveries in the
      43.9--90.7% range were obtained for purified samples and in the 90.1--121.6%
      range for crude extracts. The carbofuran immunoassay performance was further
      validated with respect to high-performance liquid chromatography (HPLC) with
      postcolumn derivatization and fluorescence detection (EPA Method 531.1). Samples
      were spiked with carbofuran at several concentrations and analyzed as blind
      samples by ELISA and HPLC after SPE cleanup. The correlation between methods was
      very good (y = 0.90x + 2.66, r(2)() = 0.958, n = 25), with HPLC being more
      precise than ELISA (mean coefficients of variation of 4.1 and 11.5%,
      respectively). The immunoassay was then applied to the analysis of nonpurified
      extracts of the same samples. Results also compared very well with those obtained
      by HPLC on purified samples (y = 1.02x + 10.44, r(2)() = 0.933, n = 29).
      Therefore, the developed immunoassay is a suitable method for the quantitative
      and reliable determination of carbofuran in fruits and vegetables even without
      sample cleanup, which saves time and money and considerably increases the sample
      throughput.

PMID- 11308316
TI  - PCR-SSCP: a simple method for the authentication of grouper (Epinephelus guaza),
      wreck fish (Polyprion americanus), and Nile perch (Lates niloticus) fillets.
AB  - A method of DNA analysis has been developed to verify the authenticity of grouper
      (Epinephelus guaza), wreck fish (Polyprion americanus), and Nile perch (Lates
      niloticus) fillets. A short fragment (208 bp) of the mitochondrial 12S rRNA gene
      was amplified by the polymerase chain reaction and analyzed by single-strand
      conformation polymorphism to get species-specific patterns of single-stranded DNA
      (ssDNA). DNA strands were separated by native polyacrylamide gel electrophoresis
      and visualized by silver staining. Discrimination among the three fish species
      studied was possible, because each one expressed a specific ssDNA pattern.

PMID- 11308317
TI  - Different tocopherols and the relationship between two methods for determination
      of primary oxidation products in fish oil.
AB  - The effectiveness of 2.32 mmol/kg (approximately 1000 ppm) of alpha-, gamma-, or
      delta-tocopherol (TOH), as well as different levels of alpha TOH, on the
      formation of hydroperoxides in fish oil was studied by monitoring the peroxide
      value (POV) and the formation of conjugated dienes (CD) during storage at 30
      degrees C. The same order of antioxidant activity was observed by both methods.
      Linear regression of POV on CD showed that these data were strongly correlated
      (r(2) > or = 0.98). The value of the slope of the regression lines, however,
      differed substantially and decreased with increasing hydrogen-donating ability of
      the different tocopherols and with increasing alpha TOH concentration. It is
      suggested that this is due, at least in part, to the contribution from hydroxy
      compounds to the CD measurements and a greater contribution from hydroperoxy
      epidioxides (two peroxide groups per conjugated diene unit) to the POV than to
      the CD value. The degrees of formation of both these groups of oxidation products
      are expected to be influenced by the rate of scavenging of lipid peroxyl and
      alkoxyl radicals by tocopherol (alpha TOH > gamma TOH > delta TOH).

PMID- 11308318
TI  - Centrifugal precipitation chromatography -- a novel chromatographic system for
      fractionation of polymeric pigments from black tea and red wine.
AB  - A novel chromatographic system was developed and first applied to the
      fractionation of polymeric pigments from black tea and red wine. Centrifugal
      precipitation chromatography (CPC) generates solvent gradients through a long
      separation channel under a centrifugal force field. Tea and wine extracts are
      precipitated in a hexane- or methyl tert-butyl ether-rich environment and are
      exposed to a gradually increasing ethanol concentration. This causes a repetitive
      precipitation and dissolution of the biopolymers along the channel. Consequently,
      they are eluted in the order of their solubility in the organic solvent. It is
      shown by HPLC analysis of the separated fractions that monomers elute first,
      whereas fractionated polymers can be found at the end of the chromatographic run.
      This novel method allows gentle fractionation of polymeric tea and wine
      constituents and also has potential for use in preparative-scale separations.

PMID- 11308319
TI  - Comparison of solvent extraction and microwave extraction for release of dimethyl
      sulfide from cereals and canola.
AB  - Natural levels of dimethyl sulfide (DMS) in newly harvested wheat, barley, paddy,
      and canola were determined by gas chromatography using a flame photometric
      detector in sulfur mode. The two methods involved determination of DMS in the
      headspace of cereal or oilseed samples (1) after extraction with microwaves and
      (2) after a traditional approach using 25% KBr solution. Quantitative results
      from each method were similar, and therefore both methods are suitable for the
      determination of DMS in grains and oilseeds. However, the microwave procedure has
      several advantages; for example, results are obtained very quickly, and only a
      small amount of sample is required.

PMID- 11308320
TI  - Analysis of proanthocyanidin cleavage products following acid-catalysis in the
      presence of excess phloroglucinol.
AB  - The analysis of proanthocyanidin cleavage products after acid-catalysis in the
      presence of excess phloroglucinol was investigated. In the developed analytical
      method, a solution of 0.1 N HCl in methanol, containing 50 g/L phloroglucinol and
      10 g/L ascorbic acid was prepared. The proanthocyanidin of interest was reacted
      in this solution (5 g/L) at 50 degrees C for 20 min, and afterward combined with
      5 volumes of 40 mM aqueous sodium acetate before analysis by reversed-phase HPLC
      using an aqueous acetic acid and methanol gradient. This procedure was used to
      investigate the composition of proanthocyanidins isolated from the seed and skin
      tissue of Vitis vinifera L. berries. The results compared favorably to results
      obtained when benzyl mercaptan was used as the trapping nucleophile, indicating
      that phloroglucinol is an effective reagent for this analysis.

PMID- 11308321
TI  - LC/ES-MS detection of hydroxycinnamates in human plasma and urine.
AB  - Hydroxycinnamates are components of many fruits and vegetables, being present in
      particularly high concentrations in prunes. An abundance of phenolic compounds in
      the diet has been associated with reduced heart disease mortality. However,
      little is known about the absorption and metabolism of these metabolites after
      normal foods are consumed. An LC--electrospray--MS method was developed to
      measure the concentration of caffeic acid in human plasma and urine, but it can
      also be applied to ferulic acid and chlorogenic acid. The limit of detection was
      found to be 10.0 nmol/L for caffeic acid and 12.5 nmol/L for ferulic and
      chlorogenic acids. The method was tested on samples of plasma and urine collected
      from volunteers who consumed a single dose of 100 g of prunes and increased
      levels were observed, demonstrating that the method is capable of detecting
      changes in hydroxycinnamate levels induced by dietary consumption.

PMID- 11308322
TI  - Screening of intestinal microflora for effective probiotic bacteria.
AB  - Increasing consumer awareness of health-promoting intestinal bacteria has fueled
      the addition of viable probiotic bacteria as functional ingredients in certain
      foods. However, to effectively market the enhanced attributes of these foods, the
      added probiotic bacteria need to have scientific credibility. The scientific
      rationale for using many of the strains of probiotic bacteria currently on the
      market is weak. Furthering the current understanding of what features a bacterium
      needs to have for effective probiotic functionality will enable the selection of
      strains with a more credible scientific rationale. To screen for effective
      strains, one must understand the microbial diversity in the intestines of healthy
      individuals. The advent of molecular tools has greatly enhanced our ability to
      accomplish this. These tools comprise genetic fingerprinting, specific probes,
      molecular speciation, and techniques for the in situ analysis of specific
      microbial groups in the intestine. This review will detail these scientific
      approaches and how their impact will improve criteria for selection of probiotic
      bacteria.

PMID- 11308323
TI  - Expression and purification of glycosylated bovine beta-casein (L70S/P71S) in
      Pichia pastoris.
AB  - Post-translational glycosylation of bovine beta-casein (L70S/P71S) that results
      in Asn(68)-linked glycan on the protein was obtained in up to 30% of total beta
      casein expressed in the methylotrophic yeast Pichia pastoris. Among the
      growth/induction media used, buffered minimal glycerol (BMG)/buffered minimal
      methanol (BMM) media were best for the production of glycosylated bovine beta
      casein, indicating pH-dependent glycosylation. Glycosylated bovine beta-casein
      (L70S/P71S) expressed in P. pastoris was purified to homogeneity by the
      combination of ammonium sulfate fractionation, Concanavalin A--Sepharose affinity
      column, and Mono Q anion-exchange FPLC. The purified glycosylated bovine beta
      casein was specific only to Concanavalin A, and the oligosaccharide structure of
      glycosylated beta-casein was of high-mannose type. Unlike the hyperglycosylation
      that occurred in yeast, the majority of bovine beta-casein was not
      hyperglycosylated in P. pastoris, and its molecular weight was estimated to be
      33.6 kDa. Glycosylated bovine beta-casein was normally phosphorylated to the same
      degree as native bovine beta-casein.

PMID- 11308324
TI  - Suppression effect of soy isoflavones on nitric oxide production in RAW 264.7
      macrophages.
AB  - Genistein, daidzein, and glycitein, as primary isoflavones in soybeans, are
      reported to have beneficial effects on atherosclerosis, chronic inflammatory
      diseases, and cancers that are conducted by nitric oxide (NO) injury. The
      objectives of this study were to investigate the effects and mechanisms of these
      soy isoflavones on the inducible nitric oxide synthase (iNOS) system in
      lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Genistein, daidzein,
      and glycitein dose-dependently suppress NO production (IC(50) = 50 microM) in
      supernatants of LPS-activated macrophages as measured on the basis of nitrite
      accumulation. In addition, direct inhibition of iNOS activity, determined by
      means of the conversion of L-[(3)H]arginine to L-[(3)H]citrulline, and markedly
      reduced iNOS protein and mRNA levels, evaluated by means of Western blot and RT
      PCR, respectively, were found in homogenates of LPS-activated cells treated with
      each isoflavone. Moreover, genistein was found to have a greater inhibitory
      effect on NO production but no significant effect on iNOS activity or protein and
      gene expression to daidzein and glycitein. These observations reveal that the
      suppression of NO production by genistein, daidzein, and glycitein might be due
      to the inhibition of both the activity and expression of iNOS in LPS-activated
      macrophages. The result suggests that soy isoflavones might attenuate excessive
      NO generation at inflammatory sites.

PMID- 11308325
TI  - Chemical characterization of the high molecular weight material extracted with
      hot water from green and roasted arabica coffee.
AB  - The polysaccharides present in coffee infusions are known to contribute to the
      organoleptic characteristics of the drink, such as the creamy sensation perceived
      in the mouth known as "body", the release of aroma substances, and the stability
      of espresso coffee foam. To increase the knowledge about the origin, composition,
      and structure of the polysaccharide fraction, the high molecular weight material
      (HMWM) was extracted with hot water from two green and roasted ground arabica
      coffees: Costa Rica (wet processed) and Brazil (dry processed). The
      polysaccharides present in the green coffees HMWM were arabinogalactans (62%),
      galactomannans (24%), and glucans, and those found in roasted coffees were
      galactomannans (69%) and arabinogalactans (28%). The polysaccharides of the HMWM
      of the roasted coffees were less branched than those of the green coffees. The
      major green coffee proteins had molecular weights of 58 and 38 kDa, and the 58
      kDa protein had two subunits, of 38 and 20 kDa, possibly linked by disulfide
      bonds. The protein fraction obtained from roasted coffees had only a defined band
      with < or =14 kDa and a diffuse band with >200 kDa. The majority of the
      galactomannans were precipitated with solutions of 50% ethanol, and the size
      exclusion chromatography of the roasted fractions showed coelution of
      polysaccharides, proteins, phenolics, and brown compounds. The use of strong
      hydrogen and hydrophobic dissociation conditions allowed us to conclude that the
      phenolics and brown compounds were linked by covalent bonds to the polymeric
      material.

PMID- 11308326
TI  - Behavior of Triticum durum Desf. arabinoxylans and arabinogalactan peptides
      during industrial pasta processing.
AB  - Three industrial pasta processing lines for different products (macaroni,
      capellini and instant noodles) were sampled at three subsequent stages (semolina,
      extruded, and dried end products) in the process. Arabinoxylans (AX) and
      arabinogalactan peptides (AGP) were analyzed. Although very low endoxylanase
      activities were measured, the level of water-extractable AX (WE-AX) increased,
      probably because of mechanical forces. No change was observed in the level and
      structural characteristics of AGP. The WE-AX molecular weight (MW) profiles
      showed a very small shift toward lower MW profiles; those of AGP revealed no
      changes as a result of the production process. After separation of WE-AX and AGP,
      (1)H NMR analysis and gas chromatography of the alditol acetates obtained
      following hydrolysis, reduction, and acetylation revealed no changes in the
      arabinose substitution profile of the WE-AX samples during pasta processing. At
      optimal cooking times, WE-AX losses in the cooking water are small (maximally
      5.9%). However, the loss of AGP is more pronounced (maximally 25.0%). Overcooking
      led to more losses of both components.

PMID- 11308327
TI  - Changes in low molecular weight phenolic compounds in Spanish, French, and
      American oak woods during natural seasoning and toasting.
AB  - The evolution of low molecular weight polyphenols in Spanish oak heartwood of
      Quercus robur,Quercus petraea, Quercus pyrenaica, and Quercus faginea was studied
      by HPLC, in relation to the processing of wood in barrel cooperage. The
      polyphenolic composition of Spanish woods subjected to natural seasoning for 3
      years and to the toasting process was studied in relation to those of French oak
      of Q. robur (Limousin) and Q. petraea (Allier) and American oak of Q. alba
      (Missouri), which are habitually used in cooperage. The concentrations of benzoic
      and cinnamic acids and aldehydes of Spanish woods increased during seasoning
      depending on the duration of this process and in the same way as those of French
      and American woods. The process having the main influence on the phenolic
      composition of wood was the toasting. It led to high increases in the
      concentration of phenolic aldehydes and acids, especially cinnamic aldehydes
      (sinapic and coniferylic aldehydes), followed by benzoic aldehydes
      (syringaldehyde and vanillin) and benzoic acids (syringic and vanillic acids).
      This polyphenolic composition in Spanish oak species evolved during toasting as
      in French and American oak, but quantitative differences were found, which were
      especially important in American species with respect to the others.

PMID- 11308328
TI  - Artificial neural network-based predictive model for bacterial growth in a
      simulated medium of modified-atmosphere-packed cooked meat products.
AB  - The data of Devilieghere et al. (Int. J. Food Microbiol. 1999, 46, 57--70) on
      bacterial growth in a simulated medium of modified-atmosphere-packed cooked meat
      products was processed for estimating maximum specific growth rate mu(max) and
      lag phase lambda of Lactobacillus sake using artificial neural networks-based
      model (ANNM) computation. The comparison between ANNM and response surface
      methodology (RSM) model showed that the accuracy of ANNM prediction was higher
      than that of RSM. Two-dimensional and three-dimensional plots of the response
      surfaces revealed that the relationships of water activity a(w), temperature T,
      and dissolved CO(2) concentration with mu(max) and lambda were complicated, not
      just linear or second-order relations. Furthermore, it was possible to compute
      the sensitivity of the model outputs against each input parameter by using ANNM.
      The results showed that mu(max) was most sensitive to a(w), T, and dissolved
      CO(2) in this order; whereas lambda was sensitive to T the most, followed by
      a(w), and dissolved CO(2) concentrations.

PMID- 11308329
TI  - Identification of a new form of lipid transfer protein (LTP1) in wheat seeds.
AB  - Recently, this laboratory has isolated from barley and beer extract an isoform of
      lipid transfer protein (LTP1), which was not fully sequenced (Jegou, S.; Douliez,
      J. P.; Molle, D.; Boivin, P.; Marion, D. J. Agric. Food Chem. 2000, 48, 5023-
      5029). It was named LTP1b and exhibited a molecular weight 294 Da higher than
      that of the known LTP1. This paper reports the finding of an LTP1 isoform in
      wheat that also exhibits an excess of 294 Da compared to the native protein.
      Amino acid sequencing, reduction and alkylation, and mass spectrometry showed
      that this new LTP1b possesses the same N-terminal sequence as the native LTP1,
      suggesting that the difference resides in the binding of an adduct which has a
      molecular weight of 294 Da. The aim of the present paper is to highlight various
      biophysical techniques that afford the identification of such an isoform-like
      LTP1 and to correlate this finding with other isoforms of LTP1 that were isolated
      from other plants but not fully sequenced.

PMID- 11308330
TI  - Evidence for surfactant solubilization of plant epicuticular wax.
AB  - The solubilization of isolated, reconstituted tomato (Lycopersicon esculentum
      Mill.) fruit and broccoli (Brassica oleracaea var. botrytis L.) leaf epicuticular
      waxes (ECW) by nonionic octylphenoxypolyethoxy ethanol surfactant (Triton X-100)
      was demonstrated in a model system by TLC and fluorescence analysis using pyrene
      as a fluorescent probe. ECW was solubilized at or above the surfactant critical
      micelle concentration; solubilization increased with an increase in micelle
      concentration. As shown by the fluorescence quenching of pyrene, surfactant
      solubilization of the ECW increased rapidly for the first 12 h, then approached a
      plateau, increased linearly with an increase in temperature (22--32 degrees C),
      and decreased linearly with the log of the polyoxyethylene chain length (range 5-
      40 oxyethylenes). These data are discussed in relation to surfactant effects on
      phytotoxicity and performance of foliar spray application of agrochemicals.

PMID- 11308331
TI  - Toxico-kinetics, recovery, and metabolism of napropamide in goats following a
      single high-dose oral administration.
AB  - Toxicokinetic behavior, recovery and metabolism of napropamide (a pre-emergent
      herbicide) and its effect on Cytochrome P(450) of liver microsomal pellet were
      studied following a single high-dose oral administration of 2.5 g kg(-1) and
      continuous (7 days) oral administration of 500 mg kg(-1) in black Bengal goat.
      Napropamide was detected in blood at 15 min and the maximum quantity was
      recovered at 3 h after administration. The absorption rate constant (Ka) value
      was low indicating poor absorption from the gastrointestinal tract. High
      elimination half-life (t(1/2) beta) and low body clearance (Cl(B)) values coupled
      with higher transfer of compound from tissue to central compartment (K(21))
      suggest that napropamide persisted in the blood for a long time, i.e., after 72 h
      of oral administration. The recovery percentage of napropamide, including
      metabolites, from goats varied from 75.94 to 80.08 and excretion of the parent
      compound through feces varied from 18.86 to 21.59%, indicating that a major
      portion of the orally administered napropamide was absorbed from the
      gastrointestinal tract of goat. Napropamide significantly increased the
      Cytochrome P(450) content of liver microsomal pellet. The recovery of metabolites
      from feces, urine, and tissues ranged from 4.2--6.2, 40.81--49.42, and 2.7-
      11.6%, respectively, during a 4--7 day period. The material balance of
      napropamide (including metabolites) following a single high-dose oral
      administration at 2.5 g kg(-1) during 4--7 days after dosing was found to be in
      the range of 75--80%.

PMID- 11308332
TI  - Expression, cloning, and immunological analysis of buckwheat (Fagopyrum
      esculentum Moench) seed storage proteins.
AB  - cDNA of buckwheat (Fagopyrum esculentum Moench) was isolated from immature seeds
      harvested 14 days after pollination. Two genes, designated FA02 and FA18, were
      found to encode legumin-like proteins and were expressed during seed development.
      The deduced amino acid sequence of FA02 was identical to the N-terminal amino
      acid domain of BW24KD, which was believed to be a major buckwheat allergen
      (Urisu, A.; Kondo, Y.; Morita, Y.; Yagi, E.; Tsuruta, M.; Yasaki, T.; Yamada, K.;
      Kuzuya, H.; Suzuki, M.; Titani, K.; Kurosawa, K. Isolation and characterization
      of a major allergen in buckwheat seeds. In Current Advances in Buckwheat
      Research; Shinshu University Press: Matsumoto, Japan, 1995; pp 965--974). It was
      predicted that FA02 would be cleaved to generate two separate components, a 41.3
      kDa alpha-subunit and a 21 kDa beta-subunit. Antiserum was raised against the
      deduced FA02 beta-subunit, and immunoblotting of total protein from buckwheat
      seeds (F. esculentum M. and Fagopyrum tartaricum Gaertn.) revealed that several
      groups of proteins reacted with the antiserum. Polypeptides in the 23--25 kDa
      range displayed the greatest reactivity.

PMID- 11308333
TI  - Use of electrospray mass spectrometry for mass determination of grape (Vitis
      vinifera) juice pathogenesis-related proteins: a potential tool for varietal
      differentiation.
AB  - Methods based on liquid chromatography-mass spectrometry (LC-MS) and protein trap
      mass spectrometry (trap-MS) were developed to determine the complement of
      pathogenesis-related (PR) proteins in grape juice. Trap-MS was superior to LC-MS
      in terms of simplicity, rapidity, and sensitivity. Proteins with a wide range of
      masses (13--33 kDa) were found in the juices of 19 different varieties of grape
      (Vitis vinifera) and were identified as mostly PR-5 type (thaumatin-like) and PR
      3 type (chitinases) proteins. Although the PR proteins in juices of grapes are
      highly conserved, small consistent differences in molecular masses were noted
      when otherwise identical proteins were compared from different varieties. These
      differences persisted through different harvest years and in fruits grown in
      different Australian locations. With the definition of four different masses for
      PR-5 proteins (range = 21,239--21,272 Da) and nine different masses of PR-3
      proteins (range = 25,330--25,631 Da) and using statistical analysis, the methods
      developed could be used for varietal differentiation of grapes grown in several
      South Australian locations on the basis of the PR protein composition of the
      juice. It remains to be seen whether this technology can be extended to grapes
      grown worldwide and to wine and other fruit-derived products to assist with label
      integrity to the benefit of consumers.

PMID- 11308334
TI  - Characterization of sago palm (Metroxylon sagu) lignin by analytical pyrolysis.
AB  - Dioxane lignin prepared from sago palm (Metroxylon sagu) was characterized by
      analytical pyrolysis coupled to gas chromatography-mass spectrometry. Large
      abundances of the p-hydroxybenzoates ester-linked to the lignin were proven by
      analytical pyrolysis as well as by mild alkaline treatment that produced p
      hydroxybenzoic acid in 16.3% yield. Pyrolysis in the presence of
      tetramethylammonium hydroxide (TMAH) before and after alkaline treatment also
      showed the presence of ester- and ether-linked p-hydroxybenzoates. Quantitative
      results of pyrolysis showed that the sago palm lignin is of syringyl type. The
      relative abundances of TMAH/pyrolysis products derived from the syringyl beta
      aryl ether substructures were 4.9 times those of the guaiacyl equivalents. Proton
      nuclear magnetic resonance analysis also showed the presence of the p
      hydroxybenzoates and the predominance of the syringyl moiety over the guaiacyl
      ones in the sago palm lignin.

PMID- 11308335
TI  - Evaluation of polyphenolic and flavonoid compounds in honeybee-collected pollen
      produced in Spain.
AB  - Polyphenolic content, flavonoid content, and free flavonoid aglycon compounds
      were determined in 11 samples of Spanish honeybee-collected pollen. Adequate
      extraction was obtained with ethyl acetate in the determination of free flavonoid
      aglycon. Recovery (>83.6%), within-run repeatability (<6.67%), between-run
      reproducibility (<8.73%), and detection limits (1.4--1.9 mg/kg) were
      satisfactory. A total of 15 compounds were separated with gradient reversed phase
      HPLC, and 13 were identified and quantified using diode array detector. The most
      predominant compounds were flavonoid glycosides, mainly flavonols. Eighty-two
      percent of the samples contained at least 14 of the phenolic components,
      primarily rutin, quercetin, myricetin, and trans-cinnamic acid as free aglycons.
      Total phenols were present, at levels of >0.85 g/100 g in the form of non
      tannins, and flavonoids of >0.35 g/100 g, using spectrophotometric procedures.
      Rutin is the best identifier of free flavonoid aglycon compounds. A minimum
      quantity of 200 mg/kg of rutin is suggested to guarantee the nutritional and
      biological properties required in the European market.

PMID- 11308336
TI  - Nutritional evaluation of ethanol-extracted lentil flours.
AB  - Lentil flours were extracted with 80% ethanol at 25 and 50 degrees C for 1, 2, or
      3 h. The various nitrogen fractions, soluble carbohydrates, three amino acids
      (Lys, His, and Tyr), available lysine, protein digestibility, and vitamins B(1)
      and B(2) were analyzed to evaluate the effect of extraction. Extraction resulted
      in an increase in the total nitrogen content of the extracted flours, with
      extraction temperature affecting the nature of the nitrogen (protein or
      nonprotein) content. There was also a large reduction in the oligosaccharides of
      the raffinose family, although the effect of temperature was appreciable only in
      the case of stachyose. There was hardly any effect on the concentrations of the
      amino acids analyzed or on protein digestibility; however, a positive correlation
      between protein digestibility and the available lysine was recorded in the
      samples. The vitamin B(1) and B(2) contents underwent variable decreases
      depending on extraction temperature.

PMID- 11308337
TI  - Improved organoleptic and nutritive properties of bakery products supplemented
      with amino acid overproducing Saccharomyces cerevisiae yeasts.
AB  - Spontaneous yeast mutants isolated in continuous culture as resistant to toxic
      amino acid analogues, able to increase up to 40 times their free amino acid pool
      of Thr, up to 160 times their pool of Met, or up to 20 times their pool of Lys,
      were characterized with regard to properties of industrial interest. Growth rate,
      mu (h(-1)), and biomass yield, Y (g/L), of the amino acid overproducing mutants
      (AA(S)) were in many cases similar to those of the wild type, whereas their free
      amino acid content was substantially increased in laboratory and industrial media
      (molasses). Doughs fermented with 3% baker's yeast and 0.5% AA(S) mutants
      produced bakery products that displayed texture similar to those fermented with
      3.5% baker's yeast, but the former had a considerable improvement of their taste
      and aroma. On the other hand, bread content of the essential amino acids Lys,
      Met, and Thr provided by yeast was also increased.

PMID- 11308338
TI  - Preparative HPLC method for the purification of sulforaphane and sulforaphane
      nitrile from Brassica oleracea.
AB  - An extraction and preparative HPLC method has been devised to simultaneously
      purify sulforaphane and sulforaphane nitrile from the seed of Brassica oleracea
      var. italica cv. Brigadier. The seed was defatted with hexane, dried, and
      hydrolyzed in deionized water (1:9) for 8 h. The hydrolyzed seed meal was salted
      and extracted with methylene chloride. The dried residue was redissolved in a 5%
      acetonitrile solution and washed with excess hexane to remove nonpolar
      contaminants. The aqueous phase was filtered through a 0.22-microm cellulose
      filter and separated by HPLC using a Waters Prep Nova-Pak HR C-18 reverse-phase
      column. Refractive index was used to detect sulforaphane nitrile, and absorbance
      at 254 nm was used to detect sulforaphane. Peak identification was confirmed
      using gas chromatography and electron-impact mass spectrometry. Each kilogram of
      extracted seed yielded approximately 4.8 g of sulforaphane and 3.8 g of
      sulforaphane nitrile. Standard curves were developed using the purified compounds
      to allow quantification of sulforaphane and sulforaphane nitrile in broccoli
      tissue using a rapid GC method. The methodology was used to compare sulforaphane
      and sulforaphane nitrile content of autolyzed samples of several broccoli
      varieties.

PMID- 11308339
TI  - Treatment of olive oil mill wastewater by Fenton's reagent.
AB  - Wastewater from olive oil mills has been treated by means of the Fe(II)/H(2)O(2)
      system (Fenton's reagent). Typical operating variables such as reagent
      concentration (C(H(2)O(2)) = 1.0--0.2 M; C(Fe(II)) = 0.01--0.1 M) and temperature
      (T = 293--323 K) exerted a positive influence on the chemical oxygen demand and
      total carbon removal. The optimum working pH was found to be in the range 2.5-
      3.0. The exothermic nature of the process involved a significant increase of the
      temperature of the reaction media. The process was well simulated by a
      semiempirical reaction mechanism based on the classic Fenton chemistry. From the
      model, the reaction between ferric iron and hydrogen peroxide [k = 1.8 x 10(15)
      exp((-12,577 +/- 1248)/T)] was suggested to be the controlling step of the
      system. Also, the simultaneous inefficient decomposition of hydrogen peroxide [k
      = 6.3 x 10(12) exp((-11,987 +/- 2414)/T)] into water and oxygen was believed to
      play an important role in the process. On the basis of stoichiometric
      calculations for hydrogen peroxide consumption, an estimation of the process
      economy has been completed.

PMID- 11308340
TI  - Determination of the odor threshold concentrations of iodinated trihalomethanes
      in drinking water.
AB  - Iodinated trihalomethanes (ITHMs) have been usually considered the disinfection
      byproducts suspected of causing medicinal odor episodes in treated water around
      the world. The odor threshold concentration (OTC) of mixed ITHMs (bromochloroiodo
      , bromodiiodo-, chlorodiiodo-, dibromoiodo-, and dichloroiodomethane) which were
      previously synthesized -- because commercial standards are not available-- were
      determined by using two sensory techniques: flavor profile analysis (FPA),
      performed by an experienced panel trained in identifying odors and tastes in
      water; and gas chromatography coupled with olfactometry (GCO). FPA results gave a
      theoretical OTCs range from 0.1 to 8.9 microg/L and ITHMs were described as
      sweet, solvent, and medicinal products. The lowest experimental value (OTC(exp))
      obtained from the six ITHMs, 0.03 microg/L, corresponded to iodoform.

PMID- 11308341
TI  - Effect of pH and temperature on the formation of volatile compounds in
      cysteine/reducing sugar/starch mixtures during extrusion cooking.
AB  - Mixtures of cysteine, reducing sugar (xylose or glucose), and starch were
      extrusion cooked using feed pH values of 5.5, 6.5, and 7.5 and target die
      temperatures of 120, 150, and 180 degrees C. Volatile compounds were isolated by
      headspace trapping onto Tenax and analyzed by gas chromatography--mass
      spectrometry. Eighty and 38 compounds, respectively, were identified from
      extrudates prepared using glucose and xylose. Amounts of most compounds increased
      with temperature and pH. Aliphatic sulfur compounds, thiophenes, pyrazines, and
      thiazoles were the most abundant chemical classes for the glucose samples,
      whereas for xylose extrudates highest levels were obtained for non-sulfur
      containing furans, thiophenes, sulfur-containing furans, and pyrazines. 2
      Furanmethanethiol and 2-methyl-3-furanthiol were present in extrudates prepared
      using both sugars, but levels were higher in xylose samples. The profiles of
      reaction products were different from those obtained from aqueous or reduced
      moisture systems based on cysteine and either glucose or ribose.

PMID- 11308342
TI  - Countercurrent supercritical fluid extraction and fractionation of alcoholic
      beverages.
AB  - A procedure for the recovery of aromatic extracts from distilled alcoholic
      beverages by means of a countercurrent supercritical fluid extraction (CC-SFE) on
      a pilot plant scale is studied. The beverage is directly in contact with the
      carbon dioxide current in a packed column, and the extracts are recovered in two
      different fractionation cells, where the depressurization occurs. The proposed
      method allows the selective extraction of aromatic components of the brandy
      flavor, rendering a high-value concentrated extract and a colored residue without
      brandy aroma. The content in ethanol of the aromatic extract can be modified by
      tuning the extraction/fractionation conditions, rendering from 15 to 95%
      recovery. The effect of the main variables, including extraction pressure and
      quality of extracting CO(2), has been tested.

PMID- 11308343
TI  - Analysis of glycosidically bound aroma precursors in tea leaves. 2. Changes in
      glycoside contents and glycosidase activities in tea leaves during the black tea
      manufacturing process.
AB  - Glycosides are known to be precursors of the alcoholic aroma compounds of black
      tea. They are hydrolyzed by endogenous glycosidases during the manufacturing
      process. Changes in the amounts of these glycosides during the manufacturing
      process were investigated by using a capillary gas chromatographic--mass
      spectrometric analysis after trifluoroacetyl derivatization of the tea glycosidic
      fractions. Primeverosides were 3-fold more abundant than glucosides in fresh
      leaves, but they decreased greatly during the manufacturing process, especially
      during the stage of rolling. After the final stage of fermentation,
      primeverosides had almost disappeared, whereas glucosides were substantially
      unchanged. These results show that hydrolysis of the glycosides mainly occurred
      during the stage of rolling and confirm that primeverosides are the main black
      tea aroma precursors. This was also supported by the changes in the glycosidase
      activities in tea leaves. The glycosidase activities remained at a high level
      during withering but decreased drastically after rolling.

PMID- 11308344
TI  - Glycosidically bound flavor compounds of cape gooseberry (Physalis peruviana L.).
AB  - The bound volatile fraction of cape gooseberry (Physalis peruviana L.) fruit
      harvested in Colombia has been examined by HRGC and HRGC-MS after enzymatic
      hydrolysis using a nonselective pectinase (Rohapect D5L). Forty bound volatiles
      could be identified, with 21 of them being reported for the first time in cape
      gooseberry. After preparative isolation of the glycosidic precursors on XAD-2
      resin, purification by multilayer coil countercurrent chromatography and HPLC of
      the peracetylated glycosides were carried out. Structure elucidation by NMR, ESI
      MS/MS, and optical rotation enabled the identification of (1S,2S)-1-phenylpropane
      1,2-diol 2-O-beta-D-glucopyranoside (1) and p-menth-4(8)-ene-1,2-diol 1-O-alpha-L
      arabinopyranosyl-(1-6)-beta-D-glucopyranoside (2). Both glycosides have been
      identified for the first time in nature. They could be considered as immediate
      precursors of 1-phenylpropane-1,2-diol and p-menth-4(8)-ene-1,2-diol, typical
      volatiles found in the fruit of cape gooseberry.

PMID- 11308345
TI  - Identification of the main odor-active compounds in musts from French and
      Romanian hybrids by three olfactometric methods.
AB  - Three olfactometric methods (frequency of detection, time--intensity method, and
      aroma extract dilution analysis) were used to evaluate the main odorants of three
      musts obtained from French--Romanian hybrids (Valerien, Admira, and Brumariu).
      The three methods allow detection of the same odor-active compounds. The results
      obtained from these methods were closely related. Nineteen odor-active compounds
      were detected, and 13 were identified. The three methods showed the importance of
      an unidentified compound with a grape and grape juice aroma note in the three
      musts. Among the other compounds, 3-hexen-1-al, (E,Z)-2,6-nonadien-1-ol, and 1
      ccten-3-one seemed to contribute actively to the odor of Valerien must. 3
      (Methylthio)propanal and hexanal were contributors to the Admira and Brumariu
      odor. Phenylacetaldehyde was one of the main odor-active compounds in must from
      Admira.

PMID- 11308346
TI  - alpha- and beta-Thujones (herbal medicines and food additives): synthesis and
      analysis of hydroxy and dehydro metabolites.
AB  - Essential oils containing alpha- and beta-thujones are important herbal medicines
      and food additives. The thujone diastereomers are rapidly metabolized convulsants
      acting as noncompetitive blockers of the gamma-aminobutyric acid-gated chloride
      channel. Synthesis and analysis of the metabolites are essential steps in
      understanding their health effects. Oxidation of alpha- and beta-thujones as
      their 2,3-enolates with oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric
      triamide) gave the corresponding (2R)-2-hydroxythujones assigned by (1)H and
      (13)C NMR and X-ray crystallography. alpha-Thujone was converted to 4-hydroxy
      alpha- and -beta-thujones via the 3,4-enol acetate on oxidation with peracid and
      osmium tetroxide, respectively. Ozonation provided 7-hydroxy-alpha- and -beta
      thujones, and by dehydration provided the 7,8-dehydro compounds. 4,10
      Dehydrothujone was prepared from sabinene via sabinol. The hydroxy and dehydro
      derivatives are readily identified and analyzed by GC/MS as the parent compounds
      and trimethylsilyl and methyloxime derivatives. A separate study established that
      all of these compounds are metabolites of alpha- and beta-thujones.

PMID- 11308347
TI  - Partial purification, characterization, and histochemical localization of fully
      latent desert truffle (Terfezia claveryi Chatin) polyphenol oxidase.
AB  - In the present paper, a fully latent polyphenol oxidase (PPO) from desert truffle
      (Terfezia claveryi Chatin) ascocarps is described for the first time. The enzyme
      was partially purified by using phase partitioning in Triton X-114 (TX-114). The
      achieved purification was 2-fold from a crude extract, with a 66% recovery of
      activity. The interfering lipids were reduced to 13% of the original content. In
      addition, the purification gave rise to a reduction of phenolic compounds to only
      37.5%, thus avoiding the postpurification tanning of the enzyme. Latent PPO was
      activated by the anionic surfactant sodium dodecyl sulfate (SDS) or by incubation
      with trypsin. The amount of SDS necessary to obtain a maximum activation was
      dependent on the nature of the substrate. The use of SDS also permitted the
      histochemical localization of the latent enzyme within the ascocarp. Terfezia
      polyphenol oxidase was kinetically characterized using two phenolic substrates (L
      DOPA and tert-butylcatechol). The latter substrate presented inhibition at high
      substrate concentration with a K(si) of 6.3 mM. Different inhibiting agents
      (kojic and cinnamic acid, mimosine and tropolone) were also studied, tropolone
      being the most effective.

PMID- 11308348
TI  - Yeasts used as fining treatment to correct browning in white wines.
AB  - White wine was subjected to several fining treatments using baker's yeast at
      concentrations of 0.5, 1, 2, 3, 4, and 5 g/L. At all these concentration levels,
      the yeasts decreased the color of the wine in different degrees. The wine samples
      treated with the higher yeast concentration were subjected to analysis of
      phenolic compounds by HPLC and found to exhibit significantly decreased contents
      of vanillic, syringic and c-coutaric acids, and procyanidins B2 and B4, and
      colored compounds eluted at high retention times. The efficiency of the yeast
      based fining treatment (1 g/L) was compared with traditional treatments such as
      those involving the use of activated charcoal or PVPP, which were employed at the
      usual concentrations in Sherry winemaking. This yeast treatment was found to
      provide results similar to those of the activated charcoal treatment in terms of
      A(420). Likewise, significant differences in the degree of retention of various
      phenols were observed among the three treatments compared. Finally, the wine
      samples obtained with the different treatments were subjected to a sensory panel.
      All the wines were found to exhibit improved color, aroma, and flavor with
      respect to the untreated samples, although the treatment using yeast at 1 g/L
      provided the best results in terms of aroma.

PMID- 11308349
TI  - Microencapsulating properties of sodium caseinate.
AB  - Emulsions were prepared with 5% (w/v) solutions of sodium caseinate (Na Cas) and
      soy oil at oil/protein ratios of 0.25-3.0 by homogenization at 10--50 MPa.
      Emulsions were spray-dried to yield powders with 20--75% oil (w/w). Emulsion oil
      droplet size and interfacial protein load were determined. Microencapsulation
      efficiency (ME), redispersion properties, and structure of the powders were
      analyzed. The size of emulsion oil droplets decreased with increasing
      homogenization pressure but was not influenced by oil/protein ratio. Emulsion
      protein load values were highest at low oil/protein ratios. ME of the dried
      emulsions was not affected by homogenization pressure but decreased from 89.2 to
      18.8% when the oil/protein ratio was increased from 0.25 to 3.0, respectively.
      Mean particle sizes of reconstituted dried emulsions were greater than those of
      the original emulsions, particularly at high oil/protein ratios (>1.0),
      suggesting destabilization of high-oil emulsions during the spray-drying process.

PMID- 11308350
TI  - Fatty acid composition of lipids in sea buckthorn (Hippophae rhamnoides L.)
      berries of different origins.
AB  - The oil content and fatty acid composition of berries from two subspecies of sea
      buckthorn (Hippophae rhamnoides L.) were investigated. The berries of subsp.
      rhamnoides contained a higher proportion of oil in seeds (11.3% vs 7.3%, p <
      0.01), berries (3.5% vs 2.1%, p < 0.001), and seedless parts (2.8% vs 1.7%, p <
      0.01) than the berries of subsp. sinensis. Linoleic (18:2n-6) and alpha-linolenic
      acids (18:3n-3) comprised about 70% of seed oil fatty acids. Palmitoleic acid
      (16:1n-7), practically absent in the seed oil, comprised 12.1--39.0% of oil in
      pulp/peel and 8.9--31.0% of that in the whole berries. More linoleic acid (40.9%
      vs 39.1%) and less alpha-linolenic acid (26.6% vs 30.6%) was found in the seed
      oil of subsp. sinensis than in the seed oil of subsp. rhamnoides (p < 0.05). The
      proportion of palmitoleic acid was higher in the oil of berries of subsp.
      rhamnoides than the berries of subsp. sinensis (26.0% vs 21.5%, 0.05 < p < 0.1),
      but was vice versa with alpha-linolenic acid (8.8% vs 11.2%, 0.05 < p < 0.1). The
      proportions of alpha-linolenic acid correlated inversely with oleic and linoleic
      acids in the seed oil. In the oil of whole berries, the proportion of palmitoleic
      acid correlated negatively with the proportions of linoleic and alpha-linolenic
      acids.

PMID- 11308351
TI  - alpha-Glucosidase inhibitory action of natural acylated anthocyanins. 1. Survey
      of natural pigments with potent inhibitory activity.
AB  - alpha-Glucosidase (AGH) inhibitory study by natural anthocyanin extracts was
      done. As the result of a free AGH assay system, 12 anthocyanin extracts were
      found to have a potent AGH inhibitory activity; in particular, Pharbitis nil
      (SOA) extract showed the strongest maltase inhibitory activity, with an IC(50)
      value of 0.35 mg/mL, as great as that of Ipomoea batatas (YGM) extract (IC(50) =
      0.36 mg/mL). Interestingly, neither extract inhibited the sucrase activity at
      all. For the immobilized assay system, which may reflect the pharmacokinetics of
      AGH at the small intestine, SOA and YGM extracts gave more potent maltase
      inhibitory activities than those of the free AGH assay, with IC(50) values of
      0.17 and 0.26 mg/mL, respectively. Both extracts also inhibited alpha-amylase
      action, indicating that anthocyanins would have a potential function to suppress
      the increase in postprandial glucose level from starch.

PMID- 11308352
TI  - alpha-Glucosidase inhibitory action of natural acylated anthocyanins. 2. alpha
      Glucosidase inhibition by isolated acylated anthocyanins.
AB  - Four diacylated pelargonidin (Pg: SOA-4 and SOA-6), cyanidin (Cy: YGM-3), and
      peonidin (Pn: YGM-6) 3-sophoroside-5-glucosides isolated from the red flowers of
      the morning glory, Pharbitis nil cv. Scarlett O'Hara (SOA), and the storage roots
      of purple sweet potato, Ipomoea batatas cv. Ayamurasaki (YGM), were subjected to
      an alpha-glucosidase (AGH) inhibitory assay, in which the assay was performed
      with the immobilized AGH (iAGH) system to mimic the membrane-bound AGH at the
      small intestine. As a result, the acylated anthocyanins showed strong maltase
      inhibitory activities with IC(50) values of <200 microM, whereas no sucrase
      inhibition was observed. Of these, SOA-4 [Pg 3-O-(2-O-(6-O-(E-3-O-(beta-D
      glucopyranosyl)caffeyl)-beta-D-glucopyranosyl)-6-O-E-caffeyl-beta-D
      glucopyranoside)-5-O-beta-D-glucopyranoside] possessed the most potent maltase
      inhibitory activity (IC(50) = 60 microM). As a result of a marked reduction of
      iAGH inhibitory activity by deacylating the anthocyanins, that is, Pg (or Cy or
      Pn) sophoroside-5-glucoside, acylation of anthocyanin with caffeic (Caf) or
      ferulic (Fer) acid was found to be important in the expression of iAGH (maltase)
      inhibition. In addition, the result that Pg-based anthocyanins showed the most
      potent maltase inhibition, with an IC(50) value of 4.6 mM, and the effect being
      in the descending order of potency of Pg > Pn/Cy strongly suggested that no
      replacement at the 3'(5')-position of the aglycon B-ring may be essential for
      inhibiting iAGH action.

PMID- 11308353
TI  - A cyclic voltammetry method suitable for characterizing antioxidant properties of
      wine and wine phenolics.
AB  - Phenolic antioxidants are ranked by reducing strength and characterized for
      reversibility using cyclic voltammetry at a glassy carbon electrode. Phenolics
      with an ortho-diphenol group show a first oxidation peak close to 400 mV (vs.
      Ag/AgCl) in a model wine solution (12% ethanol, 0.033 M tartaric acid, adjusted
      to pH 3.6), with a linear concentration dependence below 0.01 mM. Dilution of
      white wines 10x, and red wines 400x, gave first oxidation peak currents in the
      1.5 to 2.2 microA range and 1.9 to 3.4 microC of charge passed by 500 mV,
      producing values for the concentrations of phenolic antioxidants with low
      oxidation potentials in the wines. Further peaks in the cyclic voltammograms of
      the diluted wines correspond to classes of phenolics with higher oxidation
      potentials, providing a qualitative assessment of wine phenolics based on
      reducing strength.

PMID- 11308354
TI  - Formation of a novel colored product during the Maillard reaction of D-glucose.
AB  - Reactions between reducing sugars and proteins or amino acids (Maillard reaction)
      lead to the formation of yellow to brown products (melanoidins) that are
      important for food preparation and processing, such as baking, roasting, or malt
      production. Thus far, the structures of the melanoidins have not been elucidated,
      although some structural insights have been gained from model reactions. In this
      study, D-glucose was heated with an amine and two colored compounds were detected
      by HPLC/UV--vis. After purification, the main product was identified as
      [(4aS,6R,7S,8R,8aR)-4,4a,6,7,8,8a-hexahydro-7,8-dihydroxy-6-hydroxymethyl-1,4
      dipropyl-1H-pyrano[2,3-b]pyrazine-2-yl]-1-hydroxy-3-buten-2-one (1a). For the
      minor compound (2a), some spectral data were obtained, but the structure was not
      fully characterized. 1a and 2a are the main colored compounds when the reaction
      is performed in alcoholic solution or on a cellulose surface. Thus, it was
      concluded that products with an analogous structure are important for the color
      formation of foodstuffs with low water activity.

PMID- 11308355
TI  - Identification and distribution of simple and acylated betacyanins in the
      Amaranthaceae.
AB  - Red-colored plants in the family Amaranthaceae are recognized as a rich source of
      diverse and unique betacyanins. The distribution of betacyanins in 37 species of
      8 genera in the Amaranthaceae was investigated. A total of 16 kinds of
      betacyanins were isolated and characterized by HPLC, spectral analyses, and MS.
      They consisted of 6 simple (nonacylated) betacyanins and 10 acylated betacyanins,
      including 8 amaranthine-type pigments, 6 gomphrenin-type pigments, and 2 betanin
      type pigments. Acylated betacyanins were identified as betanidin 5-O-beta
      glucuronosylglucoside or betanidin 6-O-beta-glucoside acylated with ferulic, p
      coumaric, or 3-hydroxy-3-methylglutaric acids. Total betacyanin content in the 37
      species ranged from 0.08 to 1.36 mg/g of fresh weight. Simple betacyanins (such
      as amaranthine, which averaged 91.5% of total peak area) were widespread among
      all species of 8 genera. Acylated betacyanins were distributed among 11 species
      of 6 genera, with the highest proportion occurring in Iresine herbstii (79.6%)
      and Gomphrena globosa (68.4%). Some cultivated species contained many more
      acylated betacyanins than wild species, representing a potential new source of
      these pigments as natural colorants.

PMID- 11308356
TI  - Inhibitory effect of betel quid on the volatility of methyl mercaptan.
AB  - Betel quid, a popular natural masticatory in Taiwan, is mainly composed of fresh
      areca fruit, Piper betle (leaf or inflorescence), and slaked lime paste. People
      say that halitosis disappears during betel quid chewing. In this study, the
      removal of mouth odor during betel quid chewing was discussed by using a model
      system which measured its inhibition on the volatility of methyl mercaptan.
      Results showed that crude extracts of betel quid (the mixture of areca fruit,
      Piper betle, and slaked lime paste) and extracts of the mixture of areca fruit
      and slaked lime paste exhibited marked effects on the volatility of methyl
      mercaptan, and the inhibition function increased when increasing amounts of
      slaked lime paste were added. The same condition (increased inhibition) was also
      found by replacing the slaked lime paste with alkaline salts (calcium hydroxide,
      potassium hydroxide, or sodium hydroxide). Areca fruit, the major ingredient of
      betel quid, contained abundant phenolics. However, the crude phenolic extract of
      areca fruit did not show any inhibitory activity on the volatility of methyl
      mercaptan. Great inhibitory activity occurred only when the crude phenolic
      extract of areca fruit was treated with alkali. Further studies by using gel
      filtration determined that the effect probably came from the oxidative
      polymerization of phenolics of areca fruit after alkaline treatment.

PMID- 11308357
TI  - Isolation and characterization of antioxidative peptides from gelatin hydrolysate
      of Alaska pollack skin.
AB  - Gelatin extracted from Alaska pollack skin was hydrolyzed with serial digestions
      in the order of Alcalase, Pronase E, and collagenase using a three-step recycling
      membrane reactor. The fraction from the second step, which was hydrolyzed with
      Pronase E, was composed of peptides ranging from 1.5 to 4.5 kDa and showed high
      antioxidative activity. Two different peptides showing strong antioxidative
      activity were isolated from the hydrolysate using consecutive chromatographic
      methods including gel filtration on a Sephadex G-25 column, ion-exchange
      chromatography on a SP-Sephadex C-25 column, and high-performance liquid
      chromatography on an ODS column. The isolated peptides, P1 and P2, were composed
      of 13 and 16 amino acid residues, respectively; and both peptides contained a Gly
      residue at the C-terminus and the repeating motif Gly-Pro-Hyp. The antioxidative
      activities of the purified peptides were measured using the thiobarbituric acid
      method, and the cell viability was measured with MTT assay. The results showed
      that P2 had potent antioxidative activity on peroxidation of linoleic acid.
      Moreover, the cell viability of cultured liver cells was significantly enhanced
      by addition of the peptide. These results indicate that the purified peptide, P2,
      from gelatin hydrolysate of Alaska pollack skin is a natural antioxidant which
      has potent antioxidative activity.

PMID- 11308358
TI  - Effect of preslaughter feed withdrawal period on longissimus tenderness and the
      expression of calpains in the ovine.
AB  - The objective was to study the role of calpains in meat tenderness. Lambs were
      fasted for various periods of time to generate differences in meat tenderness and
      to determine in tandem the expression of calpain 1, calpain 2, calpain 3, and
      calpastatin. The assumption has been that increased calpain expression associated
      with an increase in tenderness indicates a role for calpain in the tenderization
      process and vice versa. Fasting lambs for 1 day caused a significant improvement
      in longissimus (LD) tenderness compared to the control. Correlations between the
      tenderness of the LD and the expression of the calpains and calpastatin were
      significant for calpains 1 and 3 but not for calpain 2 or calpastatin.
      Consequently, this study supports a role for calpains 1 and 3, but not for
      calpain 2, in the tenderization of the LD from fasted lambs during post-mortem
      aging.

PMID- 11308359
TI  - Improved storage stability of model infant formula by whey peptides fractions.
AB  - The purpose of this study was to evaluate the shelf-life stability (6 months) of
      model infant formula with whey protein hydrolysates or peptidic fractions as
      carrageenan replacers. Whey protein hydrolysates were prepared with trypsin and
      followed by ultrafiltration of the hydrolyzed mixture, and peptidic fractions
      were isolated from the ultrafiltered tryptic hydrolysate by anion- or cation
      exchange chromatography. The stability of the model infant formula was evaluated
      using a stratification method based on fat content differences between the top
      and bottom strata of the samples. With protein hydrolysate-based formulations,
      the creaming rate of the fat in the product was slightly higher than in the
      standard formulation (with carrageenan), which is indicative of lower storage
      stability. The addition of cationic fractions to model infant formula also
      resulted in lower product stability, whereas the fat creaming rate was retarded
      in anionic fraction based formulations. The physicochemical characteristics of
      certain peptides combined with the reported high emulsifying properties of
      peptidic sequences found within these fractions may account for their ability to
      act as carrageenan replacers.

PMID- 11308360
TI  - Olive fruit cell wall: degradation of cellulosic and hemicellulosic
      polysaccharides during ripening.
AB  - Cellulose and hemicelluloses obtained from the cell walls of partially
      depectinated olives have been studied at three stages of ripening (green, cherry,
      and black). Hemicelluloses were fractionated into two groups, the amounts of
      which diminished during ripening: those soluble in 4% KOH diminished between the
      cherry and black stages, whereas those soluble in 24% KOH did so between the
      green and cherry stages. Arabinoxylans, xyloglucans, and homo- and/or
      rhamnogalacturonans to a lesser extent were present in these fractions. After ion
      exchange and size exclusion chromatographies, decreases in the molecular weights
      of hemicelluloses, mainly in the neutral fractions, were observed. The amount of
      cellulose also decreased, but at the second stage of the ripening process.
      Approximately 2 mg/fruit of glucose was lost from cellulose, and the amount of
      uronic acids increased (0.23 mg/fruit).

PMID- 11308361
TI  - Quantitative analysis of surface-located triacylglycerol in intact emulsion
      particles.
AB  - The amount of triacylglycerol (TG) in the surface monolayer of intact
      phospholipid-stabilized emulsions was determined using (13)C nuclear magnetic
      resonance ((13)C NMR). (13)C NMR spectra of emulsions composed of bulk long-chain
      or medium-chain TG were prepared with [(13)C(3)]-carbonyl-enriched triolein,
      tripalmitin, or trioctanoin, and were analyzed and compared with NMR spectra of
      phosphatidylcholine vesicles with and without added TG. Identification of
      carbonyl peaks intermediate between those of phosphatidylcholine carbonyls and
      bulk TG confirmed the presence of surface TG in each emulsion. The surface of
      emulsions contained 2.2 mol % tripalmitin and 1.4 mol % triolein, but
      significantly more medium-chain TG, 9.1 mol % trioctanoin, as predicted by
      measurements of TG in phospholipid vesicles. Thus, medium-chain TGs are more
      accessible than long-chain TGs to enzymes or pro-oxidants in the continuous phase
      of phospholipid-stabilized emulsion systems. The quantitative determination of
      surface-located TG in intact particles will advance the understanding of emulsion
      colloidal properties, physicochemical stability, and metabolic behavior.

PMID- 11308362
TI  - New glycosides from Capsicum annuum L. var. acuminatum. Isolation, structure
      determination, and biological activity.
AB  - Investigation of polar extracts from ripe fruits of Capsicum annuum L. var.
      acuminatum yielded three new glycosides, capsosides A (1) and B (2) and
      capsianoside VII (3), along with seven known compounds (4-10). The chemical
      structures were elucidated mainly by extensive nuclear magnetic resonance methods
      and mass spectrometry, and the biological activities of icariside E(5) (4) were
      tested by different assays. Icariside E(5), in contrast to capsaicin, neither
      induces an increase in the intracellular levels of reactive oxygen species nor
      affects the mitochondria permeability transition, and it does not signal through
      the vanilloid receptor type 1. Interestingly, this compound protects Jurkat cells
      from apoptosis induced by the oxidative stress mediated by serum withdrawal.
      These results suggest that icariside E(5) may have antioxidant properties that
      strengthen the importance of peppers in the Mediterranean diet.

PMID- 11308363
TI  - Effect of chemical and genetic attachment of polysaccharides to proteins on the
      production of IgG and IgE.
AB  - To investigate the effect of polysaccharide attachment to proteins on the
      production of IgG and IgE, the genetic attachment of polysaccharide to lysozymes
      (G49N and R21T) using the yeast expression system (Saccharomyces cerevisiae AH
      22) and the Maillard-type polysaccharide attachment to native lysozyme and
      soybean P34 protein were attempted. The production of IgG and IgE was
      investigated by using mice immunized with the protein-polysaccharide conjugates
      or native proteins. The attachment of polysaccharide to lysozyme using the yeast
      expression system greatly suppressed the production level of IgG and IgE. The
      attachment of polysaccharide to native lysozyme and soybean P34 protein using the
      Maillard-type reaction was also found to be effective in reducing the production
      level of IgE compared to IgG.

PMID- 11308364
TI  - Properties of tomato powders as additives for food fortification and
      stabilization.
AB  - The antioxidant activities of two freeze-dried tomato powders as additives for
      food fortification and stabilization were studied. The two tomato powders were
      obtained from the whole fruit and from the pulp after "serum" separation,
      respectively. The antioxidant activity was studied by measuring (a) the
      inhibition of the singlet oxygen-catalyzed oxidation of alpha-linolenic acid, in
      the presence or absence of copper ions, as a model of the oxidative processes
      occurring in foods, and (b) the inhibition of xanthine oxidase (XOD)- and
      myeloperoxidase (MPO)-catalyzed reactions and copper-induced lipid peroxidation.
      The partial separation of "serum" decreased the freeze-drying time by 50%. The
      partially fractionated tomato powder had a 60% lower phenolic content and an 11
      fold higher lycopene content than the whole tomato powder, on a dry weight basis.
      Ascorbic acid was almost completely removed by fractionation. Both the powder
      obtained from the whole tomato and that obtained from the partially fractionated
      tomato had antioxidant activity in all the model systems used. Based on these
      results, we conclude that tomato powders have multifunctional properties, which
      could address the prevention of oxidative degradations both in foods and in vivo.
      Therefore, tomato can be regarded as source of food additives for fortification
      and stabilization, even if it is submitted to technological processes that can
      cause the loss of the more labile hydrophilic antioxidants.

PMID- 11308365
TI  - Electrophoretic and immunological analyses of almond (Prunusdulcis l.) genotypes
      and hybrids.
AB  - Aqueous extracts from sixty almond samples representing various genotypes and
      interspecies hybrids of almond, including almond-peach, were analyzed for protein
      and peptide content using electrophoresis, Western immunoblotting, and enzyme
      linked immunosorbent assay (ELISA). Nondenaturing nondissociating polyacrylamide
      gel electrophoresis (NDND-PAGE) of the aqueous extracts indicated that a single
      major storage protein (almond major protein -- AMP or amandin) dominated the
      total soluble protein composition. Denaturing SDS--PAGE analyses of the aqueous
      extracts revealed that the AMP was mainly composed of two sets of polypeptides
      with estimated molecular masses in the ranges of 38--41 kDa and 20--22 kDa,
      regardless of the source; however, distinct variations in the intensity and
      electrophoretic mobility of some bands were noted between samples. In addition to
      AMP, several minor polypeptides were also present in all the genotypes, and
      variations were seen in these as well. Regardless of the genotype, AMP was
      recognized in Western blots by rabbit polyclonal anti-AMP antibodies, mouse
      monoclonal anti-AMP antibodies (mAbs), and serum IgE from patients displaying
      strong serum anti-almond IgE reactivity. As with protein staining results,
      antibody reactivity also revealed common patterns but displayed some variation
      between samples. An anti-AMP inhibition ELISA was used to quantify and compare
      aqueous extracts for various samples. All samples (n = 60) reacted in this assay
      with a mean +/- standard deviation (sigma n) = 0.82 +/- 0.18 when compared to
      reference aqueous extract from Nonpareil designated as 1.0.

PMID- 11308366
TI  - Structure, dynamics, and stability of beta-cyclodextrin inclusion complexes of
      aspartame and neotame.
AB  - Studies of the high-intensity sweetener aspartame show that its stability is
      significantly enhanced in the presence of beta-cyclodextrin (beta-CyD). At a 5:1
      beta-CyD/aspartame molar ratio, the stability of aspartame is 42% greater in 4 mM
      phosphate buffer (pH 3.1) compared to solutions prepared without beta-CyD.
      Solution-state (1)H NMR experiments demonstrate the formation of 1:1 beta
      CyD/aspartame complexes, stabilized by the interaction of the phenyl-ring protons
      of aspartame with the H3 and H5 protons of beta-CyD. Inclusion complex formation
      clearly accounts for the observed stability enhancement of aspartame in solution.
      The formation of inclusion complexes in solution is also demonstrated for beta
      CyD and neotame, a structural derivative of aspartame containing an N-substituted
      3,3-dimethylbutyl group. These complexes are stabilized by the interaction of
      beta-CyD with both phenyl-ring and dimethylbutyl protons. Solid-state NMR
      experiments provide additional characterization, clearly demonstrating the
      formation of inclusion complexes in lyophilized solids prepared from solutions of
      beta-CyD and either aspartame or neotame.

PMID- 11308367
TI  - Synergistic action of an X-prolyl dipeptidyl aminopeptidase and a non-specific
      aminopeptidase in protein hydrolysis.
AB  - Non-specific monoaminopeptidase (AP; E.C. 3.4.11) and X-prolyl dipeptidyl
      aminopeptidase (X-PDAP; E.C. 3.4.14.5), both from Aspergillus oryzae, demonstrate
      strong synergism in hydrolyzing proline-containing peptides. Incubation of AP
      alone with the peptide Ala-Pro-Gly-Asp-Arg-Ile-Tyr-Val-His-Pro-Phe does not
      generate free amino acids. However, when AP and X-PDAP are added in combination,
      complete and immediate hydrolysis of all peptide bonds, other than X-Pro bonds,
      is observed. In the enzymatic hydrolysis of casein, soy, and gluten, degree of
      hydrolysis (DH) values of 54, 54, and 47% were achieved, respectively, when
      subtilisin (E.C. 3.4.21.62) was supplemented with AP. Addition of a third enzyme,
      X-PDAP, resulted in significantly higher DH values of 69, 72, and 64%,
      respectively, establishing the utility of this synergism in protein hydrolysis.

PMID- 11308368
TI  - Carotenoid esters in vegetables and fruits: a screening with emphasis on beta
      cryptoxanthin esters.
AB  - Carotenoids are found in food plants in free form or as fatty acid esters. Most
      studies have been carried out after saponification procedures, so the resulting
      data do not represent the native carotenoid composition of plant tissues.
      Therefore, nonsaponified extracts of 64 fruits and vegetables have been screened
      to determine the amount of carotenoid esters in food plants. Because one of the
      major problems in the quantitation of carotenoids is the availability of pure
      standard material, the total carotenoid ester content was calculated as lutein
      dimyristate equivalents. Lutein dimyristate was independently synthesized from
      lutein and myristoyl chloride. The highest ester concentrations were found in red
      chili (17.1 mg/100 g) and orange pepper (9.2 mg/100 g); most of the investigated
      fruits and vegetables showed concentrations up to 1.5 mg/100 g. Special attention
      was dedicated to beta-cryptoxanthin esters. To enable an accurate detection of
      the beta-cryptoxanthin ester content, beta-cryptoxanthin was purified from papaya
      and used for synthesis of beta-cryptoxanthin laurate, myristate, and palmitate,
      representing the major beta-cryptoxanthin esters in food plants. The study proved
      tropical and subtropical fruits to be an additional source of beta-cryptoxanthin
      esters in the human diet. The contents ranged from 8 microg/100 g beta
      cryptoxanthin laurate in Tunisian orange to 892 microg/100 g beta-cryptoxanthin
      laurate in papaya.

PMID- 11308369
TI  - Synthesis of structured lipids by transesterification of trilinolein catalyzed by
      Lipozyme IM60.
AB  - Structured lipids (SL) containing caprylic, stearic, and linoleic acids were
      synthesized by enzymatic transesterification using Lipozyme IM60. Pure
      trilinolein and free fatty acids were used as substrates. Incorporation of
      stearic acid was higher than that of caprylic acid in all parameters. Highest
      incorporations of both acids were achieved at 32 h, mole ratio of 1:4:4
      (trilinolein/caprylic/stearic acids), water content of 1% (wt %), temperature of
      55 degrees C, and 10% (wt %) enzyme load. The maximal incorporations of caprylic
      and stearic acids were 23.73 and 62.46 mol %, respectively. Reaction time, water
      content, and enzyme load had major influences on the reaction, whereas substrate
      mole ratio and temperature showed less influence. Lipozyme showed good stability
      over six reuses. Differential scanning calorimetric analysis of SL gave a melting
      profile with a very low melting peak of 0-3.3 degrees C and a solid fat content
      of 25.21% at 0 degrees C. The melting profile and solid fat content of SL were
      compared with those of fats extracted from commercially available solid and
      liquid margarine products. The data suggest that enzymatically produced SL could
      be used in liquid margarine products.

PMID- 11308370
TI  - Antioxidant activity of tocopherols, tocotrienols, and gamma-oryzanol components
      from rice bran against cholesterol oxidation accelerated by 2,2'-azobis(2
      methylpropionamidine) dihydrochloride.
AB  - The antioxidant activities of vitamin E (alpha-tocopherol, alpha-tocotrienol,
      gamma-tocopherol, and gamma-tocotrienol) and gamma-oryzanol components
      (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, and campesteryl
      ferulate) purified from rice bran were investigated in a cholesterol oxidation
      system accelerated by 2,2'-azobis(2-methylpropionamidine) dihydrochloride. All
      components exhibited significant antioxidant activity in the inhibition of
      cholesterol oxidation. The highest antioxidant activity was found for 24
      methylenecycloartanyl ferulate, and all three gamma-oryzanol components had
      activities higher than that of any of the four vitamin E components. Because the
      quantity of gamma-oryzanol is up to 10 times higher than that of vitamin E in
      rice bran, gamma-oryzanol may be a more important antioxidant of rice bran in the
      reduction of cholesterol oxidation than vitamin E, which has been considered to
      be the major antioxidant in rice bran. The antioxidant function of these
      components against cholesterol oxidation may contribute to the potential
      hypocholesterolemic property of rice bran.

PMID- 11308371
TI  - Assessment of degradation and intestinal cell uptake of carotenoids and
      chlorophyll derivatives from spinach puree using an in vitro digestion and Caco-2
      human cell model.
AB  - Although numerous studies have demonstrated the health benefits of chlorophyll
      derivatives, information regarding the digestion, absorption, and metabolism of
      these phytochemicals is quite limited. To better understand the digestion of
      these pigments, green vegetables including fresh spinach puree (FSP), heat- and
      acid-treated spinach puree (HASP), and ZnCl(2)-treated spinach puree (ZnSP) were
      subjected to an in vitro digestion method which simulates both the gastric and
      small intestinal phases of the process. Native chlorophylls were converted to Mg
      free pheophytin derivatives during digestion. Conversely, Zn-pheophytins were
      completely stable during the digestive process. Transfer of lipophilic
      chlorophyll derivatives, as well as the carotenoids lutein and beta-carotene,
      into the aqueous micellar fraction from the food matrix was quantified.
      Micellarization of total chlorophyll derivatives differed significantly (p <
      0.05) for FSP (37.6%), HASP (17.2%), and ZnSP (8.7%). Micellarization of
      chlorophyll a derivatives was determined to be significantly more efficient than
      chlorophyll b derivatives in FSP and HASP (p < 0.01), but not in ZnSP (p > 0.05).
      Intestinal cell uptake of micellarized pigments was investigated using HTB-37
      (parent) and clonal TC7 lines of human Caco-2 cells. Medium containing the
      pigment-enriched fraction generated during digestion was added to the apical
      surface of fully differentiated monolayers for 4 h. Pigments were then extracted
      from cells and analyzed by C18 HPLC with photodiode array detection. Both Caco-2
      HTB-37 and TC7 clone cells accumulated 20-40% and 5-10% of micellarized
      carotenoid and chlorophyll derivatives, respectively. These results are the first
      to demonstrate uptake of chlorophyll derivatives by human intestinal cells and to
      support the potential importance of chlorophylls as health-promoting
      phytochemicals.

PMID- 11308372
TI  - Comparative effects of phytosterol oxides and cholesterol oxides in cultured
      macrophage-derived cell lines.
AB  - The cytotoxicity of cholesterol and a mixture of beta-sitosterol/campesterol
      (50%/40%) and their oxides was examined in a cultured-derived macrophage cell
      line, C57BL/6. Cell numbers, lactate dehydrogenase (LDH) leakage, protein
      content, lipid uptake, and mitochondria dehydrogenase activity were determined
      after exposure of cell mononlayers to sterols and sterol oxides at a
      concentration of 200 microg/mL for up to 120 h. Results indicate that the oxides
      of cholesterol, beta-sitosterol, and campesterol exhibited similar patterns of
      toxicity as indicated by LDH leakage, cell viability, and mitochondria
      dehydrogenase activity. Greatest cell damage was associated with treatments
      containing 5 alpha,6 alpha-epoxide or cholesterol oxides, followed by beta
      sitosterol/campesterol oxides, cholesterol, and beta-sitosterol. The oxides of
      beta-sitosterol/campesterol caused less LDH leakage and less of an effect on
      protein content. Results of this study demonstrate that phytosterols contained in
      vegetable oils, when subjected to frying conditions, do oxidize and may cause
      cellular damage in an in vitro cell line similar to cholesterol oxides, although
      less severe.

PMID- 11308373
TI  - Formation of N-nitroso-N-methylurea in various samples of smoked/dried fish, fish
      sauce, seafoods, and ethnic fermented/pickled vegetables following incubation
      with nitrite under acidic conditions.
AB  - In continuation of our previous studies on N-nitroso-N-methylurea (NMU) formation
      in cured meats following incubation with nitrite at gastric pH, we extended the
      investigation to other foods mentioned in the title of this paper. The main
      objective was to determine whether these foods have the potential to form NMU at
      pH's that can be found in the human stomach. This was done by nitrosating an
      aliquot (5 g for fish sauce, 10 g for the others) of each with 7.25 microM to
      1.59 mM levels of sodium nitrite for 2 h at room temperature at pH 0.8--1.5 and
      measuring the amounts of NMU formed. Of the samples tested, fish sauce formed 2-
      712 ng of NMU, followed in decreasing order by herring (<0.3--688 ng); dried
      anchovy, shrimp, and other fishes (<0.3--134 ng); crab and lobster pate (<0.3-
      342 ng); sardines (6--59 ng); oysters and mussels (11--31 ng); dried squid (3--47
      ng); kimchi (7--107 ng); and Japanese pickled radish (<0.3--72 ng). Incorporation
      of 200-2000 ppm of ascorbic acid in the fish sauce and other foods, prior to
      nitrosation, appreciably inhibited such NMU formation. Although previous
      researchers in China reported NMU formation in nitrosated samples of fish sauce,
      this is the first reported formation of NMU upon nitrosation of the other foods
      mentioned above, and the first reported inhibition of such formation by added
      ascorbic acid.

PMID- 11308377
TI  - Treatment of primary cutaneous melanoma.

PMID- 11308378
TI  - CDC unveils first report on toxins in people.

PMID- 11308379
TI  - Results of CURE trial for acute coronary syndrome.

PMID- 11308380
TI  - As genes differ, so should interventions for cancer.

PMID- 11308386
TI  - Health outcomes for black and white patients in the Veterans Affairs health care
      system.

PMID- 11308387
TI  - Health outcomes for black and white patients in the Veterans Affairs health care
      system.

PMID- 11308389
TI  - Handheld cellular telephones and brain cancer risk.

PMID- 11308390
TI  - Handheld cellular telephones and brain cancer risk.

PMID- 11308391
TI  - Handheld cellular telephones and brain cancer risk.

PMID- 11308393
TI  - Association between changes in hormone replacement therapy and breast density.

PMID- 11308395
TI  - Time trends in the coprescribing of cisapride and contraindicated drugs in
      Umbria, Italy.

PMID- 11308396
TI  - In vivo detection of apoptosis in an intracardiac tumor.

PMID- 11308397
TI  - Identification of a novel common genetic risk factor for lumbar disk disease.
AB  - CONTEXT: Lumbar disk disease (LDD) is one of the most common musculoskeletal
      diseases, with a prevalence of about 5%. A tryptophan (Trp) allele (Trp2) was
      recently discovered in the COL9A2 gene that is associated with dominantly
      inherited LDD but is only present in about 4% of Finnish patients with LDD.
      OBJECTIVE: To determine if other collagen IX gene sequence variations play a role
      in the pathogenesis of LDD. DESIGN AND SETTING: Case-control study conducted from
      February 1997 to May 1998 at university hospitals in Finland. PARTICIPANTS: A
      total of 171 individuals with LDD (evaluated clinically and by magnetic resonance
      imaging or computed tomography) and 321 controls without LDD (186 healthy
      individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid
      arthritis, and 21 with chondrodysplasias). MAIN OUTCOME MEASURES: Frequencies of
      sequence variations covering the entire coding sequences and exon boundaries of
      the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the alpha1,
      alpha2, and alpha3 chains of the protein, detected by conformation-sensitive gel
      electrophoresis and confirmed by sequencing, compared between individuals with
      and without LDD. RESULTS: Mutation analysis of all 3 collagen IX genes resulted
      in identification of an Arg103-->Trp (arginine-->tryptophan) substitution in the
      alpha3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD
      cases, excluding 7 individuals who were carriers of the previously identified
      Gln326-->Trp (glutamine-->tryptophan) substitution in the alpha2 chain (Trp2
      allele), and was 4.7% among controls. The difference in the frequency was
      statistically significant (P =.000013). Presence of at least 1 Trp3 allele
      increases risk of LDD about 3-fold. CONCLUSION: This study led to the
      identification of a novel common genetic risk factor for LDD, confirming that
      genetic risk factors likely play a significant role in LDD.

PMID- 11308398
TI  - Use of statins and risk of fractures.
AB  - CONTEXT: Previous studies have reported lower fracture risks in patients taking 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To
      investigate risk of fracture among statin users. DESIGN: Case-control study of
      data from the General Practice Research Database (GPRD). SETTING: A total of 683
      general clinical practices in the United Kingdom. PATIENTS: Cases were 81 880
      patients aged 50 years or older who had a fracture of the vertebrae, clavicle,
      humerus, radius/ulna, carpus, hip, ankle, or foot occurring between the
      enrollment date of their practice into the GPRD and July 1999, paired with 81 880
      age-, sex-, and practice-matched controls. MAIN OUTCOME MEASURE: Risk of fracture
      in current users vs nonusers of statins. Odds ratios were estimated from
      conditional logistic regression and adjusted for smoking, medications and
      illnesses associated with fracture risk, and body mass index when known. RESULTS:
      The adjusted odds ratio (OR) for current use of statins compared with nonuse was
      1.01 (95% confidence interval [CI], 0.88-1.16). For forearm, hip, and vertebral
      fractures, the ORs were 1.01 (95% CI, 0.80-1.27), 0.59 (95% CI, 0.31-1.13), and
      1.15 (95% CI, 0.62-2.14), respectively. Relative to nonuse, a statin dosage of
      less than 20 mg/d (standardized to simvastatin) was associated with an adjusted
      OR of fracture of 1.13 (95% CI, 0.96-1.33); this OR was 1.07 (95% CI, 0.82-1.38)
      at dosages of 20 to 39.9 mg/d and 0.85 (95% CI, 0.47-1.53) at dosages of 40 mg/d
      or more. The adjusted OR was 0.71 (95% CI, 0.50-1.01) for statin use durations of
      0 to 3 months, 1.31 (95% CI, 0.87-1.95) for durations of 3 to 6 months, 1.14 (95%
      CI, 0.82-1.58) for durations of 6 to 12 months, and 1.17 (95% CI, 0.99-1.40) for
      durations of more than 12 months. CONCLUSION: In this study, use of statins at
      dosages prescribed in clinical practice was not associated with a reduction in
      risk of fracture.

PMID- 11308399
TI  - Cognitive behavioral therapy for treatment of chronic primary insomnia: a
      randomized controlled trial.
AB  - CONTEXT: Use of nonpharmacological behavioral therapy has been suggested for
      treatment of chronic primary insomnia, but well-blinded, placebo-controlled
      trials demonstrating effective behavioral therapy for sleep-maintenance insomnia
      are lacking. OBJECTIVE: To test the efficacy of a hybrid cognitive behavioral
      therapy (CBT) compared with both a first-generation behavioral treatment and a
      placebo therapy for treating primary sleep-maintenance insomnia. DESIGN AND
      SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted at
      a single academic medical center, with recruitment from January 1995 to July
      1997. PATIENTS: Seventy-five adults (n = 35 women; mean age, 55.3 years) with
      chronic primary sleep-maintenance insomnia (mean duration of symptoms, 13.6
      years). INTERVENTIONS: Patients were randomly assigned to receive CBT (sleep
      education, stimulus control, and time-in-bed restrictions; n = 25), progressive
      muscle relaxation training (RT; n = 25), or a quasi-desensitization (placebo)
      treatment (n = 25). Outpatient treatment lasted 6 weeks, with follow-up conducted
      at 6 months. MAIN OUTCOME MEASURES: Objective (polysomnography) and subjective
      (sleep log) measures of total sleep time, middle and terminal wake time after
      sleep onset (WASO), and sleep efficiency; questionnaire measures of global
      insomnia symptoms, sleep-related self-efficacy, and mood. RESULTS: Cognitive
      behavioral therapy produced larger improvements across the majority of outcome
      measures than did RT or placebo treatment. For example, sleep logs showed that
      CBT-treated patients achieved an average 54% reduction in their WASO whereas RT
      treated and placebo-treated patients, respectively, achieved only 16% and 12%
      reductions in this measure. Recipients of CBT also showed a greater normalization
      of sleep and subjective symptoms than did the other groups with an average sleep
      time of more than 6 hours, middle WASO of 26.6 minutes, and sleep efficiency of
      85.1%. In contrast, RT-treated patients continued to report a middle WASO of 43.3
      minutes and sleep efficiency of 78.8%. CONCLUSIONS: Our results suggest that CBT
      represents a viable intervention for primary sleep-maintenance insomnia. This
      treatment leads to clinically significant sleep improvements within 6 weeks and
      these improvements appear to endure through 6 months of follow-up.

PMID- 11308400
TI  - Predictors of cardiac events after major vascular surgery: Role of clinical
      characteristics, dobutamine echocardiography, and beta-blocker therapy.
AB  - CONTEXT: Patients who undergo major vascular surgery are at increased risk of
      perioperative cardiac complications. High-risk patients can be identified by
      clinical factors and noninvasive cardiac testing, such as dobutamine stress
      echocardiography (DSE); however, such noninvasive imaging techniques carry
      significant disadvantages. A recent study found that perioperative beta-blocker
      therapy reduces complication rates in high-risk individuals. OBJECTIVE: To
      examine the relationship of clinical characteristics, DSE results, beta-blocker
      therapy, and cardiac events in patients undergoing major vascular surgery. DESIGN
      AND SETTING: Cohort study conducted in 1996-1999 in the following 8 centers:
      Erasmus Medical Centre and Sint Clara Ziekenhuis, Rotterdam, Twee Steden
      Ziekenhuis, Tilburg, Academisch Ziekenhuis Utrecht, Utrecht, and Medisch Centrum
      Alkmaar, Alkmaar, the Netherlands; Ziekenhuis Middelheim, Antwerp, Belgium; and
      San Gerardo Hospital, Monza, Istituto di Ricovero e Cura a Carattere Scientifico,
      San Giovanni Rotondo, Italy. PATIENTS: A total of 1351 consecutive patients
      scheduled for major vascular surgery; DSE was performed in 1097 patients (81%),
      and 360 (27%) received beta-blocker therapy. MAIN OUTCOME MEASURE: Cardiac death
      or nonfatal myocardial infarction within 30 days after surgery, compared by
      clinical characteristics, DSE results, and beta-blocker use. RESULTS: Forty-five
      patients (3.3%) had perioperative cardiac death or nonfatal myocardial
      infarction. In multivariable analysis, important clinical determinants of adverse
      outcome were age 70 years or older; current or prior angina pectoris; and prior
      myocardial infarction, heart failure, or cerebrovascular accident. Eighty-three
      percent of patients had less than 3 clinical risk factors. Among this subgroup,
      patients receiving beta-blockers had a lower risk of cardiac complications (0.8%
      [2/263]) than those not receiving beta-blockers (2.3% [20/855]), and DSE had
      minimal additional prognostic value. In patients with 3 or more risk factors
      (17%), DSE provided additional prognostic information, for patients without
      stress-induced ischemia had much lower risk of events than those with stress
      induced ischemia (among those receiving beta-blockers, 2.0% [1/50] vs 10.6%
      [5/47]). Moreover, patients with limited stress-induced ischemia (1-4 segments)
      experienced fewer cardiac events (2.8% [1/36]) than those with more extensive
      ischemia (>/=5 segments, 36% [4/11]). CONCLUSION: The additional predictive value
      of DSE is limited in clinically low-risk patients receiving beta-blockers. In
      clinical practice, DSE may be avoided in a large number of patients who can
      proceed safely for surgery without delay. In clinically intermediate- and high
      risk patients receiving beta-blockers, DSE may help identify those in whom
      surgery can still be performed and those in whom cardiac revascularization should
      be considered.

PMID- 11308401
TI  - Impact of recommendations to suspend the birth dose of hepatitis B virus vaccine.
AB  - CONTEXT: In July 1999, due to concerns about thimerosal content, the American
      Academy of Pediatrics (AAP) and the Public Health Service (PHS) recommended
      suspending hepatitis B virus (HBV) vaccination at birth except for mothers who
      had positive or unknown hepatitis B surface antigen (HBsAg) status. In September
      1999, the Centers for Disease Control and Prevention recommended that hospitals
      resume HBV vaccination at birth with a new thimerosal-free vaccine. Whether the 2
      changes in recommendations within 3 months led to less-than-optimal compliance in
      hospital nurseries is unknown. OBJECTIVE: To determine hospital HBV vaccination
      policy before the recommendation for delay of HBV vaccination and 1 year later.
      DESIGN, SETTING, AND PARTICIPANTS: Survey of all 46 hospitals with obstetric
      services and neonatal nurseries in Cook County, Illinois. MAIN OUTCOME MEASURES:
      Hepatitis B virus immunization practices before July 1999 and in August 2000;
      hospital factors associated with routine HBV immunization and compliance with AAP
      and PHS recommendations. RESULTS: Before July 1999, 74% of surveyed hospital
      nurseries offered HBV vaccine to all neonates; only 39% did so in August 2000.
      Being located in the Chicago city limits (88% vs 57%; P =.02) and having an
      academic affiliation (93% vs 66%; P =.05) were positively associated with routine
      neonatal immunization before July 1999. Both academic affiliation and city
      location were associated with routine immunization in August 2000 (71% vs 25% [P
      =.003] and 60% vs 14% [P =.002], respectively) and with compliance with
      recommendations for suspension (57% vs 25% [P =.03] and 56% vs 10% [P =.001]).
      CONCLUSIONS: We documented a 35% decrease in hospital nurseries that routinely
      offered HBV immunization 1 year after the AAP and PHS recommendations were made.
      Special efforts may be required to make at-birth administration of HBV
      vaccination universal.

PMID- 11308402
TI  - HIV-associated non-Hodgkin lymphoma: incidence, presentation, and prognosis.
AB  - Patients with acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin
      lymphoma often present with multiple poor prognostic features, including
      significant tumor burden, advanced immunosuppression, and other concurrent
      morbidities. Strategies to manage such complex multiple-disease cases have often
      incorporated the assumption that prospects for long-term survival are poor and
      that intensive therapy cannot be tolerated and so is not justified. Since the
      advent of highly active antiretroviral therapy for human immunodeficiency virus
      infection, life expectancy has improved substantially for patients in whom the
      virus can be successfully suppressed. Thus, for complicated cases involving AIDS
      associated malignancy, a reassessment of treatment strategies and the potential
      for long-term survival is warranted. Here, we present the case of a patient with
      poor prognosis due to AIDS-associated lymphoma with leptomeningeal involvement,
      advanced immunosuppression, and deep venous thrombosis. The management of this
      case illustrates that a multidisciplinary approach to complex AIDS cases
      involving malignancy and concurrent morbidity can result in a return to
      functional health in affected patients. Successful strategies for achieving
      favorable outcomes currently exist with available therapies.

PMID- 11308403
TI  - Genetic risk factors for lumbar disk disease.

PMID- 11308404
TI  - Statins and fracture risk.

PMID- 11308413
TI  - A piece of my mind: lost in a dark wood: how wisdom sources can light the way.

PMID- 11308414
TI  - Disease detectives celebrate 50 years of successful sleuthing.

PMID- 11308415
TI  - Studies of Viagra offer some reassurance to men with concerns about cardiac
      effects.

PMID- 11308420
TI  - Attitudes and practices in postmortem organ procurement.

PMID- 11308421
TI  - Attitudes and practices in postmortem organ procurement.

PMID- 11308424
TI  - Protecting the privacy of family members in research.

PMID- 11308425
TI  - Protecting the privacy of family members in research.

PMID- 11308426
TI  - Protecting the privacy of family members in research.

PMID- 11308427
TI  - Protecting the privacy of family members in research.

PMID- 11308429
TI  - Glycemic control and health care costs for patients with diabetes.

PMID- 11308431
TI  - Sudden death and other risks associated with dry-sand beach holes.

PMID- 11308432
TI  - Prior alcohol consumption and mortality following acute myocardial infarction.
AB  - CONTEXT: Studies have found that individuals who consume 1 alcoholic drink every
      1 to 2 days have a lower risk of a first acute myocardial infarction (AMI) than
      abstainers or heavy drinkers, but the effect of prior drinking on mortality after
      AMI is uncertain. OBJECTIVE: To determine the effect of prior alcohol consumption
      on long-term mortality among early survivors of AMI. DESIGN AND SETTING:
      Prospective inception cohort study conducted at 45 US community and tertiary care
      hospitals between August 1989 and September 1994, with a median follow-up of 3.8
      years. PATIENTS: A total of 1913 adults hospitalized with AMI between 1989 and
      1994. MAIN OUTCOME MEASURE: All-cause mortality, compared by self-reported
      average weekly consumption of beer, wine, and liquor during the year prior to
      AMI. RESULTS: Of the 1913 patients, 896 (47%) abstained from alcohol, 696 (36%)
      consumed less than 7 alcoholic drinks/wk, and 321 (17%) consumed 7 or more
      alcoholic drinks/wk. Compared with abstainers, patients who consumed less than 7
      drinks/wk had a lower all-cause mortality rate (3.4 vs 6.3 deaths per 100 person
      years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71) as did
      those who consumed 7 or more drinks/wk (2.4 vs 6.3 deaths per 100 person-years;
      HR, 0.38; 95% CI, 0.25-0.55; P<.001 for trend). After adjusting for propensity to
      drink and other potential confounders, increasing alcohol consumption remained
      predictive of lower mortality for less than 7 drinks/wk, with an adjusted HR of
      0.79 (95% CI, 0.60-1.03), and for 7 or more drinks/wk, with an adjusted HR of
      0.68 (95% CI, 0.45-1.05; P =.01 for trend). The association was similar for total
      and cardiovascular mortality, among both men and women, and among different types
      of alcoholic beverages. CONCLUSION: Self-reported moderate alcohol consumption in
      the year prior to AMI is associated with reduced mortality following infarction.

PMID- 11308433
TI  - Moderate alcohol consumption and risk of heart failure among older persons.
AB  - CONTEXT: Heavy consumption of alcohol can lead to heart failure, but the
      relationship between moderate alcohol consumption and risk of heart failure is
      largely unknown. OBJECTIVE: To determine whether moderate alcohol consumption
      predicts heart failure risk among older persons, independent of the association
      of moderate alcohol consumption with lower risk of myocardial infarction (MI).
      DESIGN: Prospective cohort study conducted from 1982 through 1996, with a maximum
      follow-up of 14 years. SETTING AND PARTICIPANTS: Population-based sample of 2235
      noninstitutionalized elderly persons (mean age, 73.7 years; 41.2% male; 21.3%
      nonwhite) residing in New Haven, Conn, who were free of heart failure at
      baseline. Persons who reported alcohol consumption of more than 70 oz in the
      month prior to baseline were excluded. MAIN OUTCOME MEASURE: Time to first fatal
      or nonfatal heart failure event, according to the amount of alcohol consumed in
      the month prior to baseline. RESULTS: Increasing alcohol consumption in the
      moderate range was associated with decreasing heart failure rates. For persons
      consuming no alcohol (50.0%), 1 to 20 oz (40.2%), and 21 to 70 oz (9.8%) in the
      month prior to baseline, crude heart failure rates per 1000 years of follow-up
      were 16.1, 12.2, and 9.2, respectively. After adjustment for age, sex, race,
      education, angina, history of MI and diabetes, MI during follow-up, hypertension,
      pulse pressure, body mass index, and current smoking, the relative risks of heart
      failure for those consuming no alcohol, 1 to 20 oz, and 21 to 70 oz in the month
      prior to baseline were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.60
      1.02), and 0.53 (95% CI, 0.32-0.88) (P for trend =.02). CONCLUSIONS: Increasing
      levels of moderate alcohol consumption are associated with a decreasing risk of
      heart failure among older persons. This association is independent of a number of
      confounding factors and does not appear to be entirely mediated by a reduction in
      MI risk.

PMID- 11308434
TI  - Effectiveness of St John's wort in major depression: a randomized controlled
      trial.
AB  - CONTEXT: Extracts of St John's wort are widely used to treat depression. Although
      more than 2 dozen clinical trials have been conducted with St John's wort, most
      have significant flaws in design and do not enable meaningful interpretation.
      OBJECTIVE: To compare the efficacy and safety of a standardized extract of St
      John's wort with placebo in outpatients with major depression. DESIGN AND
      SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted
      between November 1998 and January 2000 in 11 academic medical centers in the
      United States. PARTICIPANTS: Two hundred adult outpatients (mean age, 42.4 years;
      67.0% female; 85.9% white) diagnosed as having major depression and having a
      baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20.
      INTERVENTION: Participants completed a 1-week, single-blind run-in of placebo,
      then were randomly assigned to receive either St John's wort extract (n = 98; 900
      mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response
      thereafter) or placebo (n = 102) for 8 weeks. MAIN OUTCOME MEASURES: The primary
      outcome measure was rate of change on the HAM-D over the treatment period.
      Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating
      Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the
      Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I).
      RESULTS: The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I
      all showed significant effects for time but not for treatment or time-by
      treatment interaction (for HAM-D scores, P<.001, P =.16, and P =.58,
      respectively). Analysis of covariance showed nonsignificant effects for BDI and
      GAF scores. The proportion of participants achieving an a priori definition of
      response did not differ between groups. The number reaching remission of illness
      was significantly higher with St John's wort than with placebo (P =.02), but the
      rates were very low in the full intention-to-treat analysis (14/98 [14.3%] vs
      5/102 [4.9%], respectively). St John's wort was safe and well tolerated. Headache
      was the only adverse event that occurred with greater frequency with St John's
      wort than placebo (39/95 [41%] vs 25/100 [25%], respectively). CONCLUSION: In
      this study, St John's wort was not effective for treatment of major depression.

PMID- 11308435
TI  - The CONSORT statement: revised recommendations for improving the quality of
      reports of parallel-group randomized trials.
AB  - To comprehend the results of a randomized controlled trial (RCT), readers must
      understand its design, conduct, analysis, and interpretation. That goal can be
      achieved only through complete transparency from authors. Despite several decades
      of educational efforts, the reporting of RCTs needs improvement. Investigators
      and editors developed the original CONSORT (Consolidated Standards of Reporting
      Trials) statement to help authors improve reporting by using a checklist and flow
      diagram. The revised CONSORT statement presented in this article incorporates new
      evidence and addresses some criticisms of the original statement. The checklist
      items pertain to the content of the Title, Abstract, Introduction, Methods,
      Results, and Comment. The revised checklist includes 22 items selected because
      empirical evidence indicates that not reporting the information is associated
      with biased estimates of treatment effect or because the information is essential
      to judge the reliability or relevance of the findings. We intended the flow
      diagram to depict the passage of participants through an RCT. The revised flow
      diagram depicts information from 4 stages of a trial (enrollment, intervention
      allocation, follow-up, and analysis). The diagram explicitly includes the number
      of participants, according to each intervention group, included in the primary
      data analysis. Inclusion of these numbers allows the reader to judge whether the
      authors have performed an intention-to-treat analysis. In sum, the CONSORT
      statement is intended to improve the reporting of an RCT, enabling readers to
      understand a trial's conduct and to assess the validity of its results.

PMID- 11308436
TI  - Use of the CONSORT statement and quality of reports of randomized trials: a
      comparative before-and-after evaluation.
AB  - CONTEXT: The Consolidated Standards for Reporting of Trials (CONSORT) statement
      was developed to help improve the quality of reports of randomized controlled
      trials (RCTs). To date, a paucity of data exists regarding whether it has
      achieved this goal. OBJECTIVE: To determine whether use of the CONSORT statement
      is associated with improvement in the quality of reports of RCTs. DESIGN AND
      SETTING: Comparative before-and-after evaluation in which reports of RCTs
      published in 1994 (pre-CONSORT) were compared with RCT reports from the same
      journals published in 1998 (post-CONSORT). We included 211 reports from BMJ,
      JAMA, and The Lancet (journals that adopted CONSORT) as well as The New England
      Journal of Medicine (a journal that did not adopt CONSORT and was used as a
      comparator). MAIN OUTCOME MEASURES: Number of CONSORT items included in a report,
      frequency of unclear reporting of allocation concealment, and overall trial
      quality score based on the Jadad scale, a 5-point quality assessment instrument.
      RESULTS: Compared with 1994, the number of CONSORT checklist items in reports of
      RCTs increased in all 4 journals in 1998, and this increase was statistically
      significant for the 3 adopter journals (pre-CONSORT, 23.4; mean change, 3.7; 95%
      confidence interval [CI], 2.1-5.3). The frequency of unclear reporting of
      allocation concealment decreased for each of the 4 journals, and this change was
      statistically significant for adopters (pre-CONSORT, 61%; mean change, -22%; 95%
      CI, -38% to -6%). Similarly, 3 of the 4 journals showed an improvement in the
      quality score for reports of RCTs, and this increase was statistically
      significant for adopter journals overall (pre-CONSORT, 2.7; mean change, 0.4; 95%
      CI, 0.1-0.8). CONCLUSION: Use of the CONSORT statement is associated with
      improvements in the quality of reports of RCTs.

PMID- 11308437
TI  - Value of flow diagrams in reports of randomized controlled trials.
AB  - CONTEXT: Diagrams of the flow of participants through a clinical trial are
      recommended in the Consolidated Standards for Reporting of Trials (CONSORT)
      statement, but it is unclear whether such flow diagrams improve the quality of
      trial reports. OBJECTIVE: To examine the information contributed by flow diagrams
      and the completeness of reporting overall in reports of randomized controlled
      trials (RCTs) published in 5 general and internal medicine journals. DESIGN AND
      SETTING: Analysis of 270 reports of RCTs published in 1998 in the Annals of
      Internal Medicine (AIM; n = 19), BMJ (n = 42), JAMA (n = 45), The Lancet (n =
      81), and The New England Journal of Medicine (NEJM; n = 83). MAIN OUTCOME
      MEASURES: Proportion of reports that included a flow diagram, information
      provided in flow diagrams, and completeness of reporting about flow of
      participants overall in flow diagrams or text. RESULTS: A total of 139 reports
      (51.5%) of RCTs included a flow diagram, but this varied widely among journals
      (AIM, 21.0%; BMJ, 38.1%; JAMA, 80.0%; The Lancet, 93.8%; and NEJM, 8.4%).
      Diagrams generally provided useful information, but only 73 (52.5%) included the
      number of participants who received allocated interventions and only 32 (23.0%)
      included the number of participants included in the analysis. In logistic
      regression analysis, overall completeness of reporting about flow of study
      participants was associated with publication of a flow diagram. CONCLUSIONS: Flow
      diagrams are associated with improved quality of reporting of randomized
      controlled trials. However, the structure of current flow diagrams is less than
      ideal. We propose a revised flow diagram that includes all important counts
      through the stages of parallel group trials.

PMID- 11308438
TI  - Physician interpretations and textbook definitions of blinding terminology in
      randomized controlled trials.
AB  - CONTEXT: When clinicians assess the validity of randomized controlled trials
      (RCTs), they commonly evaluate the blinding status of individuals in the RCT. The
      terminology authors often use to convey blinding status (single, double, and
      triple blinding) may be open to various interpretations. OBJECTIVE: To determine
      physician interpretations and textbook definitions of RCT blinding terms. DESIGN
      AND SETTING: Observational study undertaken at 3 Canadian university tertiary
      care centers between February and May 1999. PARTICIPANTS: Ninety-one internal
      medicine physicians who responded to a survey. MAIN OUTCOME MEASURES: Respondents
      identified which of the following groups they thought were blinded in single-,
      double-, and triple-blinded RCTs: participants, health care providers, data
      collectors, judicial assessors of outcomes, data analysts, and personnel who
      write the article. Definitions from 25 systematically identified textbooks
      published since 1990 providing definitions for single, double, or triple
      blinding. RESULTS: Physician respondents identified 10, 17, and 15 unique
      interpretations of single, double, and triple blinding, respectively, and
      textbooks provided 5, 9, and 7 different definitions of each. The frequencies of
      the most common physician interpretation and textbook definition were 75% (95%
      confidence interval [CI], 65%-83%) and 74% (95% CI, 52%-90%) for single blinding,
      38% (95% CI, 28%-49%) and 43% (95% CI, 24%-63%) for double blinding, and 18% (95%
      CI, 10%-28%) and 14% (95% CI, 0%-58%) for triple blinding, respectively.
      CONCLUSIONS: Our study suggests that both physicians and textbooks vary greatly
      in their interpretations and definitions of single, double, and triple blinding.
      Explicit statements about the blinding status of specific groups involved in RCTs
      should replace the current ambiguous terminology.

PMID- 11308439
TI  - Should patients with heart disease drink alcohol?

PMID- 11308440
TI  - CONSORT revised--improving the reporting of randomized trials.

PMID- 11308441
TI  - Separating continuing medical education from pharmaceutical marketing.

PMID- 11308448
TI  - Lagrangian chaos and correlated Levy flights in a non-Beltrami flow: transient
      versus long-term transport.
AB  - Long-range transport is studied numerically in a time-independent, three
      dimensional (3D) fluid flow composed of the superposition of two chains of
      alternating vortices, one horizontal and the other vertical. Tracers in this flow
      follow chaotic trajectories composed of correlated Levy flights with varying
      velocities. Locations of the chaotic regimes in the flow are compared with recent
      theories of chaos in non-Beltrami 3D flows. Growth of the variance of a
      distribution of tracers is divided into transient and long-term regimes, each
      with different growth exponents.

PMID- 11308442
TI  - Industry strongly supports continuing medical education.

PMID- 11308449
TI  - Short-time dynamics with initial correlations.
AB  - The short-time dynamics of correlated systems is strongly influenced by initial
      correlations, giving rise to an additional collision integral in the non
      Markovian kinetic equation. Exact cancellation of the two integrals is found if
      the initial state is thermal equilibrium, which is an important consistency
      criterion. Analytical results are given for the time evolution of the correlation
      energy, which are confirmed by comparisons with molecular dynamics simulations.

PMID- 11308450
TI  - Simple electronic circuit model for doubly stochastic resonance.
AB  - We have recently reported the phenomenon of doubly stochastic resonance [Phys.
      Rev. Lett. 85, 227 (2000)], a synthesis of noise-induced transition and
      stochastic resonance. The essential feature of this phenomenon is that
      multiplicative noise induces a bimodality and additive noise causes stochastic
      resonance behavior in the induced structure. In the present paper we outline
      possible applications of this effect and design a simple lattice of electronic
      circuits for the experimental realization of doubly stochastic resonance.

PMID- 11308451
TI  - "Generalized des Cloizeaux" exponent for self-avoiding walks on the incipient
      percolation cluster.
AB  - We study the asymptotic shape of self-avoiding random walks (SAW) on the backbone
      of the incipient percolation cluster in d-dimensional lattices analytically. It
      is generally accepted that the configurational averaged probability distribution
      function <P(B)(r,N)> for the end-to-end distance r of an N step SAW behaves as a
      power law for r-->0. In this work, we determine the corresponding exponent using
      scaling arguments, and show that our suggested "generalized des Cloizeaux"
      expression for the exponent is in excellent agreement with exact enumeration
      results in two and three dimensions.

PMID- 11308452
TI  - Universal eigenvector statistics in a quantum scattering ensemble.
AB  - We calculate eigenvector statistics in an ensemble of non-Hermitian matrices
      describing open quantum systems [F. Haake et al., Z. Phys. B 88, 359 (1992)] in
      the limit of large matrix size. We show that ensemble-averaged eigenvector
      correlations corresponding to eigenvalues in the center of the support of the
      density of states in the complex plane are described by an expression recently
      derived for Ginibre's ensemble of random non-Hermitian matrices.

PMID- 11308453
TI  - Entropy-based analysis of the number partitioning problem.
AB  - In this paper we apply the multicanonical method of statistical physics on the
      number partitioning problem (NPP). This problem is a basic NP-hard problem from
      computer science, and can be formulated as a spin-glass problem. We compute the
      spectral degeneracy, which gives us information about the number of solutions for
      a given cost E and cardinality difference m. We also study an extension of this
      problem for Q partitions. We show that a fundamental difference on the spectral
      degeneracy of the generalized (Q>2) NPP exists, which could explain why it is so
      difficult to find good solutions for this case.

PMID- 11308454
TI  - Stochastic rotation dynamics: a Galilean-invariant mesoscopic model for fluid
      flow.
AB  - A recently introduced stochastic model for fluid dynamics with continuous
      velocities and efficient multiparticle collisions is investigated, and it is
      shown how full Galilean-invariance can be achieved for arbitrary Mach numbers.
      Analytic expressions for the viscosity and diffusion constant are also derived
      and compared with simulation results. Long-time tails in the velocity and stress
      autocorrelation functions are measured.

PMID- 11308455
TI  - Frequency-dependent viscosity near the critical point: the scale to two-loop
      order.
AB  - The recent accurate measurements of Berg, Moldover, and Zimmerli [Phys. Rev.
      Lett. 82, 920 (1999); Phys. Rev. E 60, 4079 (1999)] of the viscoelastic effect
      near the critical point of xenon has shown that the scale factor involved in the
      frequency scaling is about twice the scale factor obtained theoretically. We show
      that this discrepancy is a consequence of using first order perturbation theory.
      Including two-loop contribution goes a long way towards removing the discrepancy.

PMID- 11308456
TI  - Nonuniversal features of forced two-dimensional turbulence in the energy range.
AB  - We examine energy spectra, fluxes, and transfers of two-dimensional forced
      incompressible turbulence with linear drag in the energy range, and find marked
      departures from 5/3 law and the idea of locality. Any attempt to bring the system
      into the "ideal cascade state" would result either in spectral (bulge) or flux
      distortion. We corroborate this observation by DNS (spectral code) and eddy
      damped quasinormal Markovian simulations. We examine the energy peak wave number
      k(p), in terms of drag coefficient lambda, and energy dissipation rate epsilon,
      and find a relation k(p) approximately C(lambda(3)/epsilon)(1/2) to hold with C
      approximately 50, but only within a limited range of parameters.

PMID- 11308457
TI  - Density-noise power fluctuations in vibrated granular media.
AB  - The noise power spectra of the fluctuations in density of a vibrated column of
      granular material are found to be time dependent. Spectral analysis of these
      noise power fluctuations shows nontrivial frequency dependences. The noise powers
      at different frequencies are also found to fluctuate in a partially correlated
      way. In most instances, the slow variations of the noise are strongly correlated
      over a broad range of frequencies. These results indicate that highly cooperative
      interactions exist between fluctuators. In contrast, effects of such strongly
      coupled fluctuators are absent in the one-dimensional parking-lot-model, one of
      the simplest systems used to provide a model for recent granular compaction
      experiments.

PMID- 11308458
TI  - Effective macroion-macroion potentials in asymmetric electrolytes.
AB  - Effective macroion-macroion potentials in solutions of macroions carrying 60
      elementary charges and either monovalent or divalent counterions have been
      calculated at different concentrations by means of Monte Carlo simulations with a
      consequent inversion of radial distribution functions according to Lyubartsev and
      Laaksonen [Phys. Rev. E 52, 3730 (1995)]. With monovalent counterions, the
      effective potentials are essentially of a Yukawa type, whereas with divalent
      ones, an attractive region appears at short separation. A charge renormalization
      scheme invoking the cell model and the assumption of a Yukawa-type potential
      works favorably only in the case of monovalent counterions.

PMID- 11308459
TI  - Simple fluids with complex phase behavior.
AB  - We find that a system of particles interacting through a simple isotropic
      potential with a softened core is able to exhibit a rich phase behavior
      including: a liquid-liquid transition in the supercooled phase, as has been
      suggested for water, a gas-liquid-liquid triple point, a freezing line with
      anomalous reentrant behavior. The essential ingredient leading to these features
      resides in the presence of two effective radii in the repulsive core. The
      potential investigated appears appropriate for a class of spherical polymeric
      micelles recently investigated.

PMID- 11308460
TI  - Crystalline smectic-B films as fluctuating systems: static and dynamic x-ray
      scattering.
AB  - Static and dynamic x-ray scattering has been used to characterize thermal
      fluctuations in free-standing smectic films in the crystalline-B phase. The
      results are remarkably similar to those in smectic-A films, in spite of the three
      dimensional positional order in the crystalline-B phase. The main difference is
      the disappearance of the characteristic Landau-Peierls instability of the smectic
      A phase. The dynamic nature of the fluctuations is explicitly demonstrated by x
      ray photon correlation spectroscopy. This fluctuation behavior of crystalline-B
      films can be attributed to the small value of the shear elastic constant C44.

PMID- 11308461
TI  - Multifractality, Levinthal paradox, and energy hypersurface.
AB  - Multifractal properties in the potential energy hypersurface of polypeptides and
      proteins are investigated. Characteristic multifractal behavior for different
      molecular systems is obtained from the f(alpha) spectra. The analysis shows that
      the dimension of the phase space of the problem influences the accessibility to
      different parts of the potential energy hypersurface. Also, we show that it is
      necessary to take into account the H-bond formation between amino acids in the
      conformational-folding search. The present findings indicate that the f(alpha)
      function describes some structural properties of a protein. The behavior of the
      f(alpha) spectra gives an alternative explanation about the Levinthal paradox.
      Furthermore, the anomalous temperature dependence of the Raman spin-lattice
      relaxation rates can be related to the perturbations in the secondary structures.

PMID- 11308462
TI  - Multiple current reversal in Brownian ratchets.
AB  - We address the problem of stationary transport of overdamped Brownian particles
      in a one-dimensional spatially periodic potential composed of N hills within one
      period. We show that in a system driven by both thermal equilibrium fluctuations
      and symmetric dichotomic fluctuations, a proper manipulation of the barrier
      heights and slopes of the potential leads to multiple drift velocity reversal.
      Under optimal conditions, the drift velocity as a function of temperature and
      intensity of dichotomic fluctuations possesses as many as N extrema of
      alternating signs. There exist N-1 values of a critical temperature which
      separate regimes of opposite directions of particle transport.

PMID- 11308463
TI  - Interpolation formula between very low and intermediate-to-high damping Kramers
      escape rates for single-domain ferromagnetic particles.
AB  - It is shown that the Mel'nikov-Meshkov formalism for bridging the very low
      damping (VLD) and intermediate-to-high damping (IHD) Kramers escape rates as a
      function of the dissipation parameter for mechanical particles may be extended to
      the rotational Brownian motion of magnetic dipole moments of single-domain
      ferromagnetic particles in nonaxially symmetric potentials of the
      magnetocrystalline anisotropy so that both regimes of damping occur. The
      procedure is illustrated by considering the particular nonaxially symmetric
      problem of superparamagnetic particles possessing uniaxial anisotropy subject to
      an external uniform field applied at an angle to the easy axis of magnetization.
      Here the Mel'nikov-Meshkov treatment is found to be in good agreement with an
      exact calculation of the smallest eigenvalue of Brown's Fokker-Planck equation,
      provided the external field is large enough to ensure significant departure from
      axial symmetry, so that the VLD and IHD formulas for escape rates of magnetic
      dipoles for nonaxially symmetric potentials are valid.

PMID- 11308464
TI  - Adaptation of autocatalytic fluctuations to diffusive noise.
AB  - Evolution of a system of diffusing and proliferating mortal reactants is analyzed
      in the presence of randomly moving catalysts. While the continuum description of
      the problem predicts reactant extinction as the average growth rate becomes
      negative, growth rate fluctuations induced by the discrete nature of the agents
      are shown to allow for an active phase, where reactants proliferate as their
      spatial configuration adapts to the fluctuations of the catalyst density. The
      model is explored by employing field theoretical techniques, numerical
      simulations, and strong coupling analysis. For d< or =2, the system is shown to
      exhibits an active phase at any growth rate, while for d>2 a kinetic phase
      transition is predicted. The applicability of this model as a prototype for a
      host of phenomena that exhibit self-organization is discussed.

PMID- 11308465
TI  - Trapping and survival probability in two dimensions.
AB  - We investigate the survival probability Phi(n,c) of particles performing a random
      walk on a two-dimensional lattice that contains static traps, which are randomly
      distributed with a concentration c, as a function of the number of steps n.
      Phi(n,c) is analyzed in terms of a scaling ansatz, which allows us to locate
      quantitatively the crossover between the Rosenstock approximation (valid only at
      early times) and the asymptotic Donsker-Varadhan behavior (valid only at long
      times). While the existence of the crossover has been postulated before, its
      exact location has not been known. Our scaling hypothesis is based on the mean
      value of the quantity S(n), the number of sites visited in an n-step walk. We
      make use of the idea of self-interacting random walks, and a "slithering" snake
      algorithm, available in the literature, and we are thus able to obtain accurate
      survival probability data indirectly by Monte Carlo simulation techniques. The
      crossover can now be determined by our method, and it is found to depend on a
      combination of c and n. It occurs at small Phi(n,c) values, which is typically
      the case for large values of n.

PMID- 11308466
TI  - Brownian motion in a magnetic field.
AB  - We derive explicit forms of Markovian transition probability densities for the
      velocity-space, phase-space, and the Smoluchowski configuration-space Brownian
      motion of a charged particle in a constant magnetic field. By invoking a
      hydrodynamical formalism for those stochastic processes, we quantify a continual
      (net on the local average) heat transfer from the thermostat to diffusing
      particles.

PMID- 11308467
TI  - Effect of long-range interactions on the scaling of the noisy Kuramoto
      Sivashinsky equation.
AB  - The effects of long-range interactions on the scaling properties of the noisy
      Kuramoto-Sivashinsky (KS) equation are studied by the dynamic renormalization
      group technique. It is found that the presence of long-range nonlinearity in the
      KS equation can produce new stable fixed points with varying critical exponents
      that depend on both the long-range interaction parameter rho and the substrate
      dimension d.

PMID- 11308468
TI  - Irreversible and reversible modes of operation of deterministic ratchets.
AB  - We discuss a problem of optimization of the energetic efficiency of a simple
      rocked ratchet. We concentrate on a low-temperature case in which the particle's
      motion in a ratchet potential is deterministic. We show that the energetic
      efficiency of a ratchet working adiabatically is bounded from above by a value
      depending on the form of ratchet potential. The ratchets with strongly asymmetric
      potentials can achieve ideal efficiency of unity without approaching
      reversibility. On the other hand we show that for any form of the ratchet
      potential a set of time protocols of the outer force exists under which the
      operation is reversible and the ideal value of efficiency eta=1 is also achieved.
      The mode of operation of the ratchet is still quasistatic but not adiabatic. The
      high values of efficiency can be preserved even under elevated temperatures.

PMID- 11308469
TI  - Slow logarithmic relaxation in models with hierarchically constrained dynamics.
AB  - A general kind of model with hierarchically constrained dynamics is shown to
      exhibit logarithmic anomalous relaxation similar to a variety of complex strongly
      interacting materials. The logarithmic behavior describes most of the decay of
      the response function.

PMID- 11308470
TI  - Boltzmann approximation of transport properties in thermal lattice gases.
AB  - The transport properties of the Grosfils, Boon, and Lallemand model, a two
      dimensional isotropic thermal lattice-gas, are evaluated in the Boltzmann
      approximation. This includes the (self)-diffusion, for which we have introduced
      an additional and passive color label to the otherwise identical particles in the
      system. Independently, those results are confirmed by the use of the decay of the
      velocity autocorrelation function. The theoretical predictions of the dynamical
      structure factors and results obtained by simulations show an excellent agreement
      up to fairly large wave vectors. In the hydrodynamic limit of small wave vectors,
      the Landau-Placzek formulas form an alternative and satisfactory description.

PMID- 11308471
TI  - Influence of auto-organization and fluctuations on the kinetics of a monomer
      monomer catalytic scheme.
AB  - We study analytically the kinetics of an elementary bimolecular reaction scheme
      of the Langmuir-Hinshelwood type taking place on a d-dimensional catalytic
      substrate. We propose a general approach that takes into account explicitly the
      influence of spatial correlations on the time evolution of the mean particle
      density. With this approach, we recover some known results concerning the time
      evolution of the mean particle density and establish others.

PMID- 11308472
TI  - Modeling experimental data in a Monte Carlo simulation.
AB  - A method is presented for modeling the structure of disordered media consistent
      with a set of experimental observations, such as scattering data. The data are
      incorporated into a conventional semigrand canonical Monte Carlo simulation by
      introducing a generalized, polydisperse composition space. This approach improves
      upon previous reverse Monte Carlo procedures in that thermodynamic consistency is
      retained. By way of example, the structure of a Lennard-Jones fluid is derived
      solely from radial distribution data.

PMID- 11308473
TI  - Operator Levy motion and multiscaling anomalous diffusion.
AB  - The long-term limit motions of individual heavy-tailed (power-law) particle jumps
      that characterize anomalous diffusion may have different scaling rates in
      different directions. Operator stable motions [Y(t):t> or =0] are limits of d
      dimensional random jumps that are scale-invariant according to c(H)Y(t)=Y(ct),
      where H is a dxd matrix. The eigenvalues of the matrix have real parts
      1/alpha(j), with each positive alpha(j)< or =2. In each of the j principle
      directions, the random motion has a different Fickian or super-Fickian diffusion
      (dispersion) rate proportional to t(1/alpha(j)). These motions have a governing
      equation with a spatial dispersion operator that is a mixture of fractional
      derivatives of different order in different directions. Subsets of the
      generalized fractional operator include (i) a fractional Laplacian with a single
      order alpha and a general directional mixing measure m(straight theta); and (ii)
      a fractional Laplacian with uniform mixing measure (the Riesz potential). The
      motivation for the generalized dispersion is the observation that tracers in
      natural aquifers scale at different (super-Fickian) rates in the directions
      parallel and perpendicular to mean flow.

PMID- 11308474
TI  - Critical branching-annihilating random walk of two species.
AB  - The effect of blocking between different species occurring in one dimension is
      investigated here numerically in the case of particles following branching and
      annihilating random walk. It is shown that two-dimensional simulations confirm
      the field theoretical results with logarithmic corrections. In one dimension,
      however, if particles exhibit hard core interaction I confirm the very recent
      predictions of Kwon et al. [Phys. Rev. Lett. 85, 1682 (2000)] that there are two
      different universality classes depending on the spatial symmetry of the offspring
      production characterized by beta(S)=0.5 and beta(A)=2. Elaborate analysis of
      simulation data shows that the order parameter exponent beta does not depend on
      initial conditions or on diffusion rates of species but strong correction to
      scaling is observed. By systematic numerical simulations the critical point
      properties have been explored and initial condition dependence of the dynamical
      exponents Z and alpha is shown. In the case of a random initial state the
      particle-density decay at the critical point follows the t(-1/4) law with
      logarithmic corrections with two offsprings.

PMID- 11308475
TI  - Relaxation of classical particles in two-dimensional anharmonic single-well
      potentials.
AB  - The canonical ensemble relaxation function of a particle in a symmetric
      anharmonic potential well in D=1 is known to exhibit slow algebraic behavior [S.
      Sen, R. S. Sinkovits and S. Chakravarti, Phys. Rev. Lett. 77, 4855 (1996); R. S.
      Sinkovits, S. Sen, J. C. Phillips, and S. Chakravarti, Phys. Rev. E 59, 6497
      (1999)]. In the present work, we report a study of relaxation of a particle in
      symmetric and asymmetric quartic anharmonic potential wells of the form V(x,y)=1
      / 2 (x(2)+Cy2)+1 / 4 (x(2)+Cy2)(2) in D=2. The relaxation in the above system is
      identical to that in D=1 wells when C=0 (since it is then a D=1 system) and C=1.
      However, for 0<C<1 and for C>>1, the frequencies associated with well dynamics
      are strongly affected and hence the power spectra are altered as a function of C.
      Our calculations suggest that the exponents of the long-time tails associated
      with the relaxation processes are insensitive to D. In closing, we comment on the
      consequences of our analysis for the study of slow dynamics in interacting many
      particle systems that are connected by harmonic springs with the individual
      particles in anharmonic potential wells.

PMID- 11308476
TI  - Coil-to-stretch transition, kink formation, and efficient barrier crossing of a
      flexible chain.
AB  - We study the thermally activated barrier crossing of a linear, flexible chain
      (polymer) under the Kramers bistable potential using the multidimensional barrier
      crossing theory and the functional integral method. We find that above a critical
      chain length or below a critical chain spring constant the chain at the barrier
      top undergoes coil-to-stretch transition, resulting in the formation of a kink.
      The emergence of the kink mode renormalizes the activation energy to a smaller
      value so as to facilitate the barrier crossing. In addition to this, the larger
      fluctuation of the polymer in the unstable region of the potential (compared to
      that in the confining well) further reduces the free energy barrier, and greatly
      enhances the crossing rate of a flexible chain. We calculate analytically the
      crossing rates and confirm the results by numerical simulations. The polymer in
      barrier crossing thus reveals its conformational flexibility and adjustment to
      external forces as characteristic features of soft matter dynamics.

PMID- 11308477
TI  - Dynamic realization of transport phenomenon in finite system.
AB  - Exploring the Fokker-Planck or Langevin type transport equation from the
      underlying dynamics, we study by exploiting the numerical simulations whether or
      not one may expect dissipative motions in a Hamilton system with finite degrees
      of freedom without introducing any statistical concept. It will be shown that the
      macro-level transport phenomenon in a finite system can be dynamically
      established from the underlying Hamilton system, and the nonlinear coupling
      between two subsystems is decisive for generating the transport phenomenon.

PMID- 11308478
TI  - Small worlds: how and why.
AB  - We investigate small-world networks from the point of view of their origin. While
      the characteristics of small-world networks are now fairly well understood, there
      is as yet no work on what drives the emergence of such a network architecture. In
      situations such as neural or transportation networks, where a physical distance
      between the nodes of the network exists, we study whether the small-world
      topology arises as a consequence of a tradeoff between maximal connectivity and
      minimal wiring. Using simulated annealing, we study the properties of a randomly
      rewired network as the relative tradeoff between wiring and connectivity is
      varied. When the network seeks to minimize wiring, a regular graph results. At
      the other extreme, when connectivity is maximized, a "random" network is
      obtained. In the intermediate regime, a small-world network is formed. However,
      unlike the model of Watts and Strogatz [Nature 393, 440 (1998)], we find an
      alternate route to small-world behavior through the formation of hubs, small
      clusters where one vertex is connected to a large number of neighbors.

PMID- 11308479
TI  - Cellular models for river networks.
AB  - A cellular model introduced for the evolution of the fluvial landscape is
      revisited using extensive numerical and scaling analyses. The basic network
      shapes and their recurrence especially in the aggregation structure are then
      addressed. The roles of boundary and initial conditions are carefully analyzed as
      well as the key effect of quenched disorder embedded in random pinning of the
      landscape surface. It is found that the above features strongly affect the
      scaling behavior of key morphological quantities. In particular, we conclude that
      randomly pinned regions (whose structural disorder bears much physical meaning
      mimicking uneven landscape-forming rainfall events, geological diversity or
      heterogeneity in surficial properties like vegetation, soil cover or type) play a
      key role for the robust emergence of aggregation patterns bearing much
      resemblance to real river networks.

PMID- 11308480
TI  - Energetic contributions to wall-particle depletion forces.
AB  - Recently, depletion forces were accounted for by a contraction of the description
      based on the integral equations theory of simple liquids [Phys. Rev. E 61, 4095
      (2000)]. The extension of those results to the case of inhomogeneous systems is
      reported here. Besides, the energetic contributions to the wall-particle
      depletion forces are studied, as they arise as soon as charge is put on some of
      the components of a binary mixture of hard spheres on the front of a hard wall.
      By charging the small particles the amplitude of the depletion attraction between
      wall and large particles is reduced, and can even become a repulsion. A similar
      effect is observed if an attractive interaction between wall and small particles
      is present.

PMID- 11308481
TI  - Weighted density functional theory of spherically inhomogeneous hard spheres.
AB  - The weighted density functional theory of hard sphere fluids proposed by Tarazona
      is applied to spherically inhomogeneous hard sphere fluids. The density profile
      of a hard sphere fluid around a hard sphere particle with structureless hard wall
      and varying radii is obtained. Our results are compared with previously obtained
      computer simulation with good agreement. We also calculate the density profile of
      a hard sphere fluid confined to spherical pores. We compare these results with
      those obtained by Calleja et al., in which both theory and computer simulation
      are used. In this case the results are also in agreement.

PMID- 11308482
TI  - Crystal structures and freezing of dipolar fluids.
AB  - We investigate the crystal structure of classical systems of spherical particles
      with an embedded point dipole at T=0. The ferroelectric ground state energy is
      calculated using generalizations of the Ewald summation technique. Due to the
      reduced symmetry compared to the nonpolar case the crystals are never strictly
      cubic. For the Stockmayer (i.e., Lennard-Jones plus dipolar) interaction three
      phases are found upon increasing the dipole moment: hexagonal, body-centered
      orthorhombic, and body-centered tetragonal. An even richer phase diagram arises
      for dipolar soft spheres with a purely repulsive inverse power law potential
      approximately r(-n). A crossover between qualitatively different sequences of
      phases occurs near the exponent n=12. The results are applicable to electro- and
      magnetorheological fluids. In addition to the exact ground state analysis we
      study freezing of the Stockmayer fluid by density-functional theory.

PMID- 11308483
TI  - Analytic dependence of the pressure and energy of an atomic fluid under shear.
AB  - Nonequilibrium molecular dynamics simulations are reported at different strain
      rates (gamma;) for a shearing atomic fluid interacting via accurate two- and
      three-body potentials. We report that the hydrostatic pressure has a strain-rate
      dependence of gamma;(2), in contrast to the gamma;(3/2) dependence predicted by
      mode-coupling theory. Our results indicate that the pressure and energy of real
      fluids may display an analytic dependence on the strain rate. This is in contrast
      to previous work using either Lennard-Jones or Weeks-Chandler-Anderson potentials
      that had shown a gamma;(3/2) dependence of pressure and energy.

PMID- 11308484
TI  - Structure of interfacial liquids: X-ray scattering studies.
AB  - We have used synchrotron x rays to study three different liquids near solid
      liquid interfaces. For either ultrathin (45-90 A) or thick ( approximately 5000
      A) liquid films on silicon substrates, we find (on the basis of diffraction peaks
      or specular reflectivity data) that the molecules form 3-6 layers at the
      interface, with plane spacings close to the molecular dimensions. Rough surfaces
      and/or impurities reduce the density oscillation amplitudes. Making the liquid
      film very thin does not observably enhance the effect, which implies that
      layering is present even at an isolated interface (i.e., in a semi-infinite
      liquid). On the other hand, predeposited impurities diffuse away from the
      interface more easily if the liquid films are thick. The liquids studied are
      nonconducting, nonpolar, and nonreactive; the molecules are roughly spherical;
      and our substrate surface has no lateral structure. Thus our observations should
      apply to any liquid near a hard wall.

PMID- 11308485
TI  - Entropy-driven demixing in spherocylinder binary mixtures.
AB  - The stability of binary fluid mixtures, with respect to a demixing transition, is
      examined within the framework of the geometrical approximation of the direct
      correlation for hard nonspherical particles. In this theory, the direct
      correlation function is essentially written in terms of the geometrical
      properties of the individual molecules, and those of the overlap region between
      two different molecules, taken at fixed separation and orientations. Within the
      present theory, the demixing spinodal line in the (rho(1),rho(2)) concentration
      plane is obtained analytically, and shown to be a quadratic function of the total
      packing fraction and the compositions. The theory is applied herein to binary
      mixtures of hard spherocylinders in the isotropic phase. Isotropic fluid-fluid
      demixing can be predicted for a large variety of sizes and aspect ratios, and the
      necessary condition for entropic demixing is a sufficiently large thickness
      difference between the two particles that belong to each of the fluids in the
      mixture. As the theory reduces exactly to the Percus-Yevick approximation for a
      hard sphere mixture, accordingly it will not predict fluid-fluid demixing for
      this particular case. Demixing is also forbidden in two other cases; for a
      mixture of spherocylinders and small spheres, and for mixtures of equally thin
      spherocylinders. The influence and competition of an ordering instability on the
      demixing is also examined. The ordering of a fluid will always be displaced
      toward higher packing fractions by the addition of a nonordering fluid, and in
      some cases the entropic demixing can dominate the entire fluid range. Although
      the present theory merges exactly with the correct Onsager limit, it is shown
      that, for intermediate cases, the results can be significantly different from
      predictions of Onsager type approaches. These discrepancies are analyzed in
      particular for the needle plus spherocylinder mixture. Finally, in view of the
      nature of the theory, it is conjectured that the predicted demixing densities
      values are rather upper bounds to what should be expected.

PMID- 11308486
TI  - Clipped random wave analysis of anisometric lamellar microemulsions.
AB  - Small-angle neutron scattering experiments were performed on C10E4-D2O-octane
      (where C10E4 is tetraethylene glycol monodecyl ether) anisometric microemulsions
      in the lamellar phase at a constant surfactant volume fraction of 20% and at the
      hydrophile-lipophile balance temperature of 22.5 degrees C. The results were
      analyzed using a clipped random wave model with a specific spectral distribution
      function developed by us previously. This enabled us to generate three
      dimensional morphologies of the microemulsions, which showed clearly that in
      sufficiently anisometric microemulsions the oil-water interface was no longer
      connected. At large anisometry isolated regions of oil or water were found, and
      the transition from a bicontinuous structure at isometry to these isolated
      micelles far from isometry goes through an intermediate cylindrical morphology
      when the oil-to-water or water-to-oil ratio is around 4 to 1. We further computed
      the joint distribution function of the mean curvature H and Gaussian curvature K
      of the entire oil-water interface for each anisometric microemulsion. In
      particular, we show the distribution of <H>, <K>, and <H2>-<H>(2) for different
      isolated regions within an oil-rich microemulsion at an oil-to-water ratio of 85%
      to 15%. These distributions allowed us to prove that the isolated regions formed
      in highly anisometric microemulsions were small and had spherical topology.

PMID- 11308487
TI  - Effective attraction between like-charged colloids in a two-dimensional plasma.
AB  - The existence of attractions between like-charged colloids immersed in ionic
      solution has been discovered in recent experiments. This phenomenon contradicts
      the predictions of Derjaguin-Landau-Verwey-Overbeek and indicates a failure of
      mean-field theory. We study a toy model based on a two-dimensional one-component
      plasma, which is exactly soluble at one particular coupling constant. We show
      that colloidal interaction results from a competition between ion-ion repulsion
      and longer ranged ion-void attraction.

PMID- 11308488
TI  - Measuring shear-induced self-diffusion in a counterrotating geometry.
AB  - The novel correlation method to measure shear-induced self-diffusion in
      concentrated suspensions of noncolloidal hard spheres which we developed recently
      [J. Fluid Mech. 375, 297 (1998)] has been applied in a dedicated counterrotating
      geometry. The counterrotating nature of the setup enables experiments over a
      wider range of well-controlled dimensionless time (gamma;Deltat in the range 0.03
      3.5, compared to 0.05-0.6 in previous experiments; here gamma; denotes the shear
      rate and Deltat the correlation time). The accessible range of timescales made it
      possible to study the nature of the particle motion in a more detailed way. The
      wide radius geometry provides a well-defined flow field and was designed such
      that there is optical access from different directions. As a result, shear
      induced self-diffusion coefficients could be determined as a function of particle
      volume fraction straight phi (0.20-0.50) in both the vorticity and velocity
      gradient direction. A transition could be observed to occur for gamma;Deltat of
      O(1), above which the particle motion is diffusive. The corresponding self
      diffusion coefficients do not increase monotonically with particle volume
      fraction, as has been suggested by numerical calculations and theoretical
      modeling of Brady and Morris [J. Fluid Mech. 348, 103 (1997)]. After an
      exponential growth up to straight phi=0.35, the diffusion coefficients level off.
      The experiments even suggest the existence of a maximum around straight phi=0.40.
      The results are in good agreement with experimental literature data of Phan and
      Leighton [J. Fluid Mech. (submitted)], although these measurements were performed
      for much larger values of the dimensionless time gamma;Deltat.

PMID- 11308489
TI  - Caging of a d-dimensional sphere and its relevance for the random dense sphere
      packing.
AB  - We analyze the caging of a hard sphere (i.e., the complete arrest of all
      translational motions) by randomly distributed static contact points on the
      sphere surface for arbitrary dimension d>/=1, and prove that the average number
      of uncorrelated contacts required to cage a sphere is <N>(d)=2d+1. Computer
      simulations, which confirm this analytical result, are also used to model the
      effect of correlations between contacts that occur in real hard-sphere systems.
      Our analysis predicts an average coordination number of 4.79 (+/-0.02) for caged
      spheres, which agrees surprisingly well with the experimental coordination number
      for random sphere packings reported by Mason [Nature 217, 733 (1968)]. This
      result supports the physical picture that the coordination number in random dense
      sphere packings is primarily determined by caging effects. It also suggests that
      it should be possible to construct such packings from a local caging rule.

PMID- 11308490
TI  - Coexistence of large amplitude stationary structures in a model of reaction
      diffusion system.
AB  - The two-variable reaction-diffusion model of a chemical system describing the
      spatiotemporal evolution to large amplitude stationary periodical structures in a
      one-dimensional open, continuous-flow, unstirred reactor is investigated.
      Numerical solutions show that the structures are generated by divisions of the
      traveling impulse and its stopping at the boundary of the system. Analyses of
      projections of numerical solutions on the phase plane of two variables elaborated
      in the present paper allow qualitative explanation of the results. The
      coexistence of the large amplitude stationary periodical structures is shown. A
      number of coexisting structures grows strongly with increasing length of the
      reactor and may be as large as one wishes. The relationship of these results to
      biological systems is stressed.

PMID- 11308491
TI  - Superposition rheology.
AB  - The interpretation of superposition rheology data is still a matter of debate due
      to lack of understanding of viscoelastic superposition response on a microscopic
      level. So far, only phenomenological approaches have been described, which do not
      capture the shear induced microstructural deformation, which is responsible for
      the viscoelastic behavior to the superimposed flow. Experimentally there are
      indications that there is a fundamental difference between the viscoelastic
      response to an orthogonally and a parallel superimposed shear flow. We present
      theoretical predictions, based on microscopic considerations, for both orthogonal
      and parallel viscoelastic response functions for a colloidal system of attractive
      particles near their gas-liquid critical point. These predictions extend to
      values of the stationary shear rate where the system is nonlinearly perturbed,
      and are based on considerations on the colloidal particle level. The difference
      in response to orthogonal and parallel superimposed shear flow can be understood
      entirely in terms of microstructural distortion, where the anisotropy of the
      microstructure under shear flow conditions is essential. In accordance with
      experimental observations we find pronounced negative values for response
      functions in case of parallel superposition for an intermediate range of
      frequencies, provided that microstructure is nonlinearly perturbed by the
      stationary shear component. For the critical colloidal systems considered here,
      the Kramers-Kronig relations for the superimposed response functions are found to
      be valid. It is argued, however, that the Kramers-Kronig relations may be
      violated for systems where the stationary shear flow induces a considerable
      amount of new microstructure.

PMID- 11308492
TI  - Character of the glass transition in thin supported polymer films.
AB  - We have used ellipsometry to study the thermal expansivity of thin polystyrene
      films on silicon substrates with thicknesses of 10-200 nm. We find well-defined
      glass transitions, and detailed analysis of the expansivities shows that for
      thinner films the transition width is broadened, while the strength of the
      transition, defined by the difference between the expansivities in the liquid and
      glassy state, is reduced; the expansivity in the glassy state is higher than in
      the bulk. These phenomena are consistent with the idea that a layer of roughly
      constant thickness, of order 10 nm, near the surface of the film has liquidlike
      thermal properties at all experimental temperatures.

PMID- 11308493
TI  - Slip events and dilatancy in a sheared fine noncohesive powder.
AB  - We present experimental results of the transition from steady-state sliding to
      oscillatory motion for a fine noncohesive powder, sheared in an annular cell. The
      onset of instability is compared to the Dieterich-Ruina model for solid friction.
      We present data showing that at low velocity and close to the transition, the
      major sliding jumps are preceded by a short or long period of unstable plastic
      yielding of the granular matter. This ambivalent behavior suggests that the jumps
      are initiated when the sliding overcomes a critical velocity. During the stick
      slip motion, the dilatancy of the powder bed has been also observed: the slippage
      is associated with a compaction whose value increases with the jump in the
      friction coefficient.

PMID- 11308494
TI  - Effect of nonzero chain diameter on "DNA" condensation.
AB  - We present a simple model to investigate the effect of chain diameter on
      multivalent-counterion-induced attractions between two charged chains. In our
      minimal model, the chains are rigid rods of diameter D with a uniform charge
      density on the surface, and the counterions are point ions. As a function of the
      separation between two rods, we find a repulsive barrier in the free energy whose
      height increases with D. We have also explored the effect of counterion valency Z
      on the interaction. For parameters characteristic of DNA, we find that a minimum
      valency of Z=3 is required to produce condensation. We also find that the shape
      of the potential is fairly insensitive to Z for Z>/=3. These results are
      consistent with experimental observations of DNA condensation.

PMID- 11308495
TI  - Entropy-driven phase separation and configurational correlations on a lattice:
      some rigorous results.
AB  - We prove that if there is a phase separation in a fully packed (FP) athermal
      system, it must be between pure components only. We then rigorously demonstrate
      that no phase separation in an athermal FP state of hard particle mixtures on a
      lattice is possible merely due to size disparity or nonadditivity, if the
      configurations are weakly correlated, i.e., are quasirandom. We consider a
      mixture of linear polymers at all packing fractions and argue that no phase
      separation is possible in an athermal state. The last result also applies to a
      mixture of flexible particles and hard dimers. Our results contradict many recent
      numerical results.

PMID- 11308496
TI  - Extremal collision sequences of particles on a line: optimal transmission of
      kinetic energy.
AB  - The transmission of kinetic energy through chains of inelastically colliding
      spheres is investigated for the case of constant coefficient of restitution
      epsilon=const and impact-velocity-dependent coefficient epsilon(v) for
      viscoelastic particles. We derive a theory for the optimal distribution of
      particle masses which maximize the energy transfer along the chain and check it
      numerically. We found that for epsilon=const, the mass distribution is a
      monotonous function which does not depend on the value of epsilon. In contrast,
      for epsilon(v) the mass distribution reveals a pronounced maximum, depending on
      the particle properties and on the chain length. The system investigated
      demonstrates that even for small and simple systems, the velocity dependence of
      the coefficient of restitution may lead to new effects with respect to the same
      systems under the simplifying approximation epsilon=const.

PMID- 11308497
TI  - Crossings and writhe of flexible and ideal knots.
AB  - The data of ideal knots [Nature, 384, 142 (1996)] are reanalyzed and the average
      crossing number of the ideal knots <X>(ideal) shows a nonlinear behavior with the
      essential crossing number C. Supplemented with our Monte Carlo simulations using
      the bond fluctuation model on flexible knotted polymers, our analysis indicates
      that <X>(ideal) varies nonlinearly with both C and the corresponding average
      crossing number of the flexible knot, which is contrary to previous claims. Our
      extensive simulation data on the average crossing number of flexible knots
      suggest that it varies linearly with the square root of C. Furthermore, our data
      on the average writhe number <Wr> indicate that various knots are classified into
      holonomous groups, and <Wr> has a quantized linear increment with C in all four
      knot groups in our study.

PMID- 11308498
TI  - Time-dependent fiber bundles with local load sharing.
AB  - Fiber bundle models, where fibers have random lifetimes depending on their load
      histories, are useful tools in explaining time-dependent failure in heterogeneous
      materials. Such models shed light on diverse phenomena such as fatigue in
      structural materials and earthquakes in geophysical settings. Various asymptotic
      and approximate theories have been developed for bundles with various geometries
      and fiber load-sharing mechanisms, but numerical verification has been hampered
      by severe computational demands in larger bundles. To gain insight at large size
      scales, interest has returned to idealized fiber bundle models in 1D. Such
      simplified models typically assume either equal load sharing (ELS) among
      survivors, or local load sharing (LLS) where a failed fiber redistributes its
      load onto its two nearest flanking survivors. Such models can often be solved
      exactly or asymptotically in increasing bundle size, N, yet still capture the
      essence of failure in real materials. The present work focuses on 1D bundles
      under LLS. As in previous works, a fiber has failure rate following a power law
      in its load level with breakdown exponent rho. Surviving fibers under fixed loads
      have remaining lifetimes that are independent and exponentially distributed. We
      develop both new asymptotic theories and new computational algorithms that
      greatly increase the bundle sizes that can be treated in large replications
      (e.g., one million fibers in thousands of realizations). In particular we develop
      an algorithm that adapts several concepts and methods that are well-known among
      computer scientists, but relatively unknown among physicists, to dramatically
      increase the computational speed with no attendant loss of accuracy. We consider
      various regimes of rho that yield drastically different behavior as N increases.
      For 1/2< or =rho< or =1, ELS and LLS have remarkably similar behavior (they have
      identical lifetime distributions at rho=1) with approximate Gaussian bundle
      lifetime statistics and a finite limiting mean. For rho>1 this Gaussian behavior
      also applies to ELS, whereas LLS behavior diverges sharply showing brittle,
      weakest volume behavior in terms of characteristic elements derived from critical
      cluster formation. For 0<rho<1/2, ELS and LLS again behave similarly, but the
      bundle lifetimes are dominated by a few long-lived fibers, and show
      characteristics of strongest link, extreme value distributions, which apply
      exactly to rho=0.

PMID- 11308499
TI  - Infiltration through porous media.
AB  - We study the kinetics of infiltration in which contaminant particles, which are
      suspended in a flowing carrier fluid, penetrate a porous medium. The progress of
      the "invader" particles is impeded by their trapping on active "defender" sites
      which are on the surfaces of the medium. As the defenders are used up, the
      invader penetrates further and ultimately breaks through. We study this process
      in the regime where the particles are much smaller than the pores so that the
      permeability change due to trapping is negligible. We develop a family of
      microscopic models of increasing realism to determine the propagation velocity of
      the invasion front, as well as the shapes of the invader and defender profiles.
      The predictions of our model agree qualitatively with experimental results on
      breakthrough times and the time dependence of the invader concentration at the
      output. Our results also provide practical guidelines for improving the design of
      deep bed filters in which infiltration is the primary separation mechanism.

PMID- 11308500
TI  - Physics of polymer melts.
AB  - We have mapped the physics of polymer melts onto a time-dependent Landau-Ginzburg
      |psi|(4) field theory using techniques of functional integration. Time in the
      theory is simply a label for the location of a given monomer along the extent of
      a flexible chain. With this model, one can show that the limit of infinitesimal
      concentration of a polymer melt corresponds to a dynamic critical phenomenon. The
      transition to the entangled state is also shown to be a critical point. For
      larger concentrations, when the role of fluctuations is reduced, a mean-field
      approximation is justifiably employed to show the existence of tubelike
      structures reminiscent of Edwards' model.

PMID- 11308501
TI  - Numerical study of surface-induced reorientation and smectic layering in a
      nematic liquid crystal.
AB  - Surface-induced profiles of both nematic and smectic order parameters in a
      nematic liquid crystal, ranging from an orienting substrate to "infinity," were
      evaluated numerically on the basis of an extended Landau theory. In order to
      obtain a smooth behavior of the solutions at "infinity," a boundary energy
      functional was derived by linearizing the Landau energy around its equilibrium
      solutions. We find that the intrinsic wave number of the smectic structure, which
      plays the role of a coupling between nematic and smectic order, strongly
      influences the director reorientation. Whereas the smectic order is rapidly
      decaying when moving away from the surface, the uniaxial nematic order parameter
      shows an oscillatory behavior close to the substrate, accompanied by a nonzero
      local biaxiality.

PMID- 11308502
TI  - X-ray study of oil-microemulsion and oil-water interfaces in ternary amphiphilic
      systems.
AB  - We present x-ray reflectivity and diffuse scattering measurements from the
      interfaces between oil-rich and microemulsion bulk phases and between oil-rich
      and water-rich phases in three-component microemulsion systems (consisting of
      water, alkane, and C(i)E(j), where the last represents n-alkyl polyglycol ether
      with i=4,6,10 and j=1,2,4). The x-ray measurements are analyzed with a two
      parameter fit that determines the interfacial roughness, varying from 25 A to 160
      A, and the interfacial tension, varying from 1.4 mN/m to 0.03 mN/m, for these
      samples. Although a nonmonotonic profile at the oil-microemulsion interface is
      not observed, these measurements exclude the presence of oscillating profiles
      with repeat distances greater then 500 A.

PMID- 11308503
TI  - Interface localization-delocalization transition in a symmetric polymer blend: a
      finite-size scaling Monte Carlo study.
AB  - Using extensive Monte Carlo simulations, we study the phase diagram of a
      symmetric binary (AB) polymer blend confined into a thin film as a function of
      the film thickness D. The monomer-wall interactions are short ranged and
      antisymmetric, i.e., the left wall attracts the A component of the mixture with
      the same strength as the right wall does the B component, and this gives rise to
      a first order wetting transition in a semi-infinite geometry. The phase diagram
      and the crossover between different critical behaviors is explored. For large
      film thicknesses we find a first order interface localization-delocalization
      transition, and the phase diagram comprises two critical points, which are the
      finite film width analogies of the prewetting critical point. Using finite-size
      scaling techniques we locate these critical points, and present evidence of a two
      dimensional Ising critical behavior. When we reduce the film width the two
      critical points approach the symmetry axis straight phi=1/2 of the phase diagram,
      and for D approximately 2R(g) we encounter a tricritical point. For an even
      smaller film thickness the interface localization-delocalization transition is
      second order, and we find a single critical point at straight phi=1/2. Measuring
      the probability distribution of the interface position, we determine the
      effective interaction between the wall and the interface. This effective
      interface potential depends on the lateral system size even away from the
      critical points. Its system size dependence stems from the large but finite
      correlation length of capillary waves. This finding gives direct evidence of a
      renormalization of the interface potential by capillary waves in the framework of
      a microscopic model.

PMID- 11308504
TI  - Hidden photoalignment of liquid crystals in the isotropic phase.
AB  - We found the effect of a hidden photoalignment of a dye-doped nematic liquid
      crystal (LC) on a nonphotosensitive polymer surface after polarized irradiation
      of the cell in the isotropic phase. We observed that irradiation resulted in a
      uniform planar orientation of the LC after cooling to the mesophase. The
      direction of a light-induced easy axis on the polymer can be either parallel or
      perpendicular to the polarization of the incident light, depending on the light
      intensity. We attribute this behavior to two mechanisms of photoalignment: light
      induced adsorption of dye molecules on the substrate, and anisotropic desorption
      in a previously adsorbed dye layer. The experimental results on photoalignment of
      a LC on a thin dye film confirm our model.

PMID- 11308505
TI  - Structure of spontaneous periodic deformations in hybrid aligned nematic layers.
AB  - Periodic deformations, arising spontaneously in hybrid nematic layers were
      investigated numerically. So called splay stripes, which appear when the surface
      anchoring energy of the planar alignment was greater than that of the homeotropic
      alignment, were considered. Conical degeneration of the anchoring is assumed. The
      role of the layer thickness d and the anchoring strength W was studied by means
      of the dimensionless control parameter gamma=Wd/k(11) defined for each boundary.
      The saddle-splay elastic constant k(24) was varied within the limits given by
      general Ericksen inequalities. The director distributions were calculated. Two
      structures with different properties were distinguished: one for k(24)<0 (mode 1)
      and the other for k(24)>0 (mode 2). For given nematic liquid crystal parameters,
      mode 1 existed when gamma exceeds some critical value. Below this critical gamma,
      the director distortion decayed and the spatial period simultaneously diverged to
      infinity. As a result mode 1 disappeared and the homogeneously planar orientation
      was realized. The width of the stripes also increased infinitely for high gamma.
      No upper limit of the gamma range in which mode 1 could exist was found. Mode 2
      existed for gamma ranging from 0 to a certain critical value. Above this limit
      the periodic structure was replaced by the homogeneous hybrid alignment as a
      consequence of an infinite increase of the stripes' width. When k(24)>0 was
      sufficiently small, the gamma range was bounded from below, and a homogeneously
      planar orientation appeared for low gamma. The visibility of the stripes between
      crossed polarizers was estimated by calculations of light transmission. In
      general, the stripes for k(24)<0 turned out to be more distinct than that for
      k(24)>0.

PMID- 11308506
TI  - Field-induced behaviors near the smectic-A-smectic-C * alpha phase transition of
      an antiferroelectric liquid crystal.
AB  - We have experimentally and theoretically investigated the electric-field effect
      on the smectic-A-smectic-C(*)(alpha) phase transition of an antiferroelectric
      liquid crystal4-(1-methyl-heptyloxycarbonyl)phenyl 4(')-octylcarbonyloxybiphenil
      4-carboxylate. From the microscopic observations under electric fields and the
      measurements of the D-E hysteresis loop and apparent tilt angle, the E (electric
      field)-T (temperature) phase diagram was established, in which a tricritical
      point was found. From the dielectric measurements under dc electric fields, a
      soft mode inducing the transition was observed. Furthermore, we have developed a
      phenomenological theory under dc fields to analyze the experimental results. The
      origin of the soft mode observed under fields was clarified and the temperature
      dependence of the relaxation frequency was obtained by the analyses.

PMID- 11308507
TI  - Surface states in nearly modulated systems.
AB  - A Landau model is used to study the phase behavior of the surface layer for
      magnetic and cholesteric liquid-crystal systems that are at or near a Lifshitz
      point marking the boundary between modulated and homogeneous bulk phases. The
      model incorporates surface and bulk fields and includes a term in the free energy
      proportional to the square of the second derivative of the order parameter in
      addition to the usual term involving the square of the first derivative. In the
      limit of vanishing bulk field, three distinct types of surface ordering are
      possible: a wetting layer, a nonwet layer having a small deviation from bulk
      order, and a different nonwet layer with a large deviation from bulk order that
      decays nonmonotonically as the distance from the wall increases. In particular,
      the large deviation nonwet layer is a feature of systems at the Lifshitz point
      and also those systems having only homogeneous bulk phases.

PMID- 11308508
TI  - Disjoining pressure and thinning transitions in smectic-A liquid crystal films.
AB  - The contact angle between a free standing film of a smectic-A liquid crystal and
      its meniscus is different from zero. It increases independently of the meniscus
      size when the film thickness decreases. This angle provides a very precise
      measurement of the film tension and of the interactions between the two free
      surfaces. This interaction is attractive and can be qualitatively explained
      within the framework of the de Gennes theory of the presmectic state. According
      to this model, the attraction is caused by an increase of the smectic order
      parameter at the free surface. This phenomenon also explains the metastability of
      very thin smectic films above the bulk smectic-A-nematic phase transition. The
      temperatures T(N) of spontaneous thinning from N layers to N-1 layers is measured
      in the smectic phase of the liquid crystal 8CB (octylcyanobiphenyl).

PMID- 11308509
TI  - Investigations of orientational order for an antiferroelectric liquid crystal by
      polarized Raman scattering measurements.
AB  - The orientational ordering of the antiferroelectric liquid crystal molecules, 4
      (1-methyl-heptyloxycarbonyl)phenyl 4(')-octyloxybiphenyl-4-carboxylate was
      investigated in the series of the successive smectic phases by means of polarized
      Raman scattering measurement without any external field. An improved equation for
      the analysis of the polarized Raman intensity was derived as a function of an
      incident laser polarization and the orientational order parameters. Even in the
      chiral smectic phases, some apparent orientational order parameters could be
      defined by the proper corrections for the smectic layer structure and an optical
      disturbance. An unusual change of the orientational order parameters was observed
      with decrease in temperature. It was concluded that the irregular variation of
      the order parameter stemmed from the biaxiality of the molecular orientational
      distribution, which was attributed to the hindrance of molecular rotation around
      its long axis.

PMID- 11308510
TI  - Generalized mean-field potential description for ferroelectric ordering in
      nematic liquid crystals.
AB  - Ferroelectric ordering in a nematic liquid crystal system is described using a
      generalized mean-field potential including effective potentials for both axial
      and polar interactions. From a self-consistent numerical analysis, a complete
      phase diagram is obtained as a function of the axial and polar interaction
      potential strengths. The obtained phase diagram exhibits not only the usual
      isotropic-nematic phase transition but also nematic-ferroelectric nematic and
      direct isotropic-ferroelectric nematic phase transitions with a tricritical point
      among the phases. The phase transition behaviors and the angular orientational
      distribution function of the molecules were investigated by studying the
      dependence of the polar and the axial order parameters on the reduced
      temperature. Moreover, the other polar order parameters responsible for second
      harmonic generation (SHG) were also investigated in the generalized mean-field
      potential description. As a concrete example, we performed a quantitative
      analysis of the SHG signal reported previously in a lyotropic poly L-glutamate
      system, detailing the relationship between the angular distribution function and
      the order parameters based on our potential model. This clarifies the nature of
      the ferroelectric phase responsible for SHG in nematics.

PMID- 11308511
TI  - Molecular dynamics study of slip at the interface between immiscible polymers.
AB  - Nonequilibrium molecular dynamics simulations were used to study the structural
      properties and viscous response of interfaces in binary blends of symmetric
      polymers. The polymers were made immiscible by increasing the repulsion between
      unlike species. As the repulsion increased, the interface narrowed, and the
      fraction of chain ends in the interfacial region increased. The viscosity in the
      interfacial region eta(I) was lower than the bulk viscosity, leading to an
      effective slip boundary condition at the interface. As the degree of
      immiscibility increased, the interfacial viscosity decreased, and the slip length
      increased. When the radius of gyration of the chains was much larger than the
      interfacial width, eta(I) was independent of chain length. As predicted by de
      Gennes and co-workers, eta(I) corresponds to the bulk viscosity of chains whose
      radius of gyration is proportional to the width of the interfacial region.

PMID- 11308512
TI  - Bubble propagation in a helicoidal molecular chain.
AB  - We study the propagation of very large amplitude localized excitations in a model
      of DNA that takes explicitly into account the helicoidal structure. These
      excitations represent the "transcription bubble," where the hydrogen bonds
      between complementary bases are disrupted, allowing access to the genetic code.
      We propose these kinds of excitations in alternative to kinks and breathers. The
      model has been introduced by Barbi et al. [Phys. Lett. A 253, 358 (1999)], and up
      to now it has been used to study on the one hand low amplitude breather
      solutions, and on the other hand the DNA melting transition. We extend the model
      to include the case of heterogeneous chains, in order to get closer to a
      description of real DNA; in fact, the Morse potential representing the
      interaction between complementary bases has two possible depths, one for A-T and
      one for G-C base pairs. We first compute the equilibrium configurations of a
      chain with a degree of uncoiling, and we find that a static bubble is among them;
      then we show, by molecular dynamics simulations, that these bubbles, once
      generated, can move along the chain. We find that also in the most unfavorable
      case, that of a heterogeneous DNA in the presence of thermal noise, the
      excitation can travel for well more than 1000 base pairs.

PMID- 11308513
TI  - Delayed stochastic differential model for quiet standing.
AB  - A physiological quiet standing model, described by a delayed differential
      equation, subject to a white noise perturbation, is proposed to study the
      postural control system of human beings. It has been found that the white noise
      destabilizes the equilibrium state, and inertia accelerates the destabilizing
      process, and that the position of a person is detected and processed by the
      person's nervous system with a delay. This paper focuses on the analysis of Hopf
      bifurcation and its stability in this context. Based on the analytical
      predictions confirmed by numerical simulations, it has been shown that the
      posture of a person is controlled in such a way that possible amplitude
      oscillations are minimized.

PMID- 11308515
TI  - Viscoelastic properties of actin-coated membranes.
AB  - In living cells, cytoskeletal filaments interact with the plasma membrane to form
      structures that play a key role in cell shape and mechanical properties. To study
      the interaction between these basic components, we designed an in vitro self
      assembled network of actin filaments attached to the outer surface of giant
      unilamellar vesicles. Optical tweezers and single-particle tracking experiments
      are used to study the rich dynamics of these actin-coated membranes (ACM). We
      show that microrheology studies can be carried out on such an individual
      microscopic object. The principle of the experiment consists in measuring the
      thermally excited position fluctuations of a probe bead attached biochemically to
      the membrane. We propose a model that relates the power spectrum of these thermal
      fluctuations to the viscoelastic properties of the membrane. The presence of the
      actin network modifies strongly the membrane dynamics with respect to a fluid,
      lipid bilayer one. It induces first a finite (omega=0) two-dimensional (2D) shear
      modulus G(0)(2D) approximately 0.5 to 5 microN/m in the membrane plane. Moreover,
      the frequency dependence at high frequency of the shear modulus [G(')(2D)(f )
      approximately f(0.85+/-0.07)] and of the bending modulus (kappa(ACM)(f)
      approximately f(0.55+/-0.21)) demonstrate the viscoelastic behavior of the
      composite membrane. These results are consistent with a common exponent of 0.75
      for both moduli as expected from our model and from prior measurements on actin
      solutions.

PMID- 11308514
TI  - Prediction of electroencephalographic spectra from neurophysiology.
AB  - A recent neurophysical model of propagation of electrical waves in the cortex is
      extended to include a physiologically motivated subcortical feedback loop via the
      thalamus. The electroencephalographic spectrum when the system is driven by white
      noise is then calculated analytically in terms of physiological parameters,
      including the effects of filtering of signals by the cerebrospinal fluid, skull,
      and scalp. The spectral power at low frequencies is found to vary as f(-1) when
      awake and f(-3) when asleep, with a breakpoint to a steeper power-law tail at
      frequencies above about 20 Hz in both cases; the f(-1) range concurs with recent
      magnetoencephalographic observations of such a regime. Parameter sensitivities
      are explored, enabling a model with fewer free parameters to be proposed, and
      showing that spectra predicted for physiologically reasonable parameter values
      strongly resemble those observed in the laboratory. Alpha and beta peaks seen
      near 10 Hz and twice that frequency, respectively, in the relaxed wakeful state
      are generated via subcortical feedback in this model, thereby leading to
      predictions of their frequencies in terms of physiological parameters, and of
      correlations in their occurrence. Subcortical feedback is also predicted to be
      responsible for production of anticorrelated peaks in deep sleep states that
      correspond to the occurrence of theta rhythm at around half the alpha frequency
      and sleep spindles at 3/2 times the alpha frequency. An additional positively
      correlated waking peak near three times the alpha frequency is also predicted and
      tentatively observed, as are two new types of sleep spindle near 5/2 and 7/2
      times the alpha frequency, and anticorrelated with alpha. These results provide a
      theoretical basis for the conventional division of EEG spectra into frequency
      bands, but imply that the exact bounds of these bands depend on the individual.
      Three types of potential instability are found: one at zero frequency, another in
      the theta band at around half the alpha frequency, and a third at the alpha
      frequency itself.

PMID- 11308516
TI  - Mechanical unfolding and refolding of proteins: an off-lattice model study.
AB  - Using an off-lattice model, we investigate the response of a protein molecule to
      external stretching and release. In particular we study the passive force in a
      protein as a function of the extension of the protein. These force-extension
      curves exhibit hysteresis loops, whose areas increase with the pulling rate and
      decrease with thermal noise. Most of these results seem to be appropriately
      described by a cusp catastrophe.

PMID- 11308517
TI  - Stretching a macromolecule in an atomic force microscope: statistical mechanical
      analysis.
AB  - We formulate the proper statistical mechanics to describe the stretching of a
      macromolecule under a force provided by the cantilever of an atomic force
      microscope. In the limit of a soft cantilever the generalized ensemble of the
      coupled molecule/cantilever system reduces to the Gibbs ensemble for an isolated
      molecule subject to a constant force in which the extension is fluctuating. For a
      stiff cantilever we obtain the Helmholtz ensemble for an isolated molecule held
      at a fixed extension with the force fluctuating. Numerical examples are given for
      poly (ethylene glycol) chains.

PMID- 11308518
TI  - Resonance-enhanced signal detection and transduction in the Hodgkin-Huxley
      neuronal systems.
AB  - The ability of signal detection and transduction of the Hodgkin-Huxley neuronal
      systems, associated with rhythmic oscillations in the presence of external
      modulations, is studied. Both inhibitory and excitatory modulations, regarded as
      the total effects of the environment in which the neurons are located, are able
      to modulate the frequencies of the rhythmic oscillations of the neurons. Either
      subthreshold or suprathreshold rhythmic oscillations can provide the neural
      system with an effect of frequency selection in processing external signal.
      Resonance among the noise, the noise-induced oscillation, and the signal enhances
      intensively the capability of the neurons in processing the weak signal,
      especially when frequency of the signal is around that of the noise-induced
      rhythmic oscillation. Thus, the neuronal system can be adjusted to an optimal
      sensitive state for signal processing through the environmental modulations.

PMID- 11308519
TI  - Role of synaptic delay in organizing the behavior of networks of self-inhibiting
      neurons.
AB  - We consider a pair of mutually coupled inhibitory neurons in which each neuron is
      also self-inhibitory. We show that the size of the synaptic delay determines the
      existence and stability of solutions. For small delays, there is no synchronous
      solution, but a stable antiphase and a stable on-state solution. For long delays,
      only the synchronous solution is stable. For intermediate delays, either the
      antiphase or synchronous solutions are stable. In contrast to prior work, for
      stability of synchrony, we only require the existence of a single slow process.

PMID- 11308520
TI  - Helix-coil transition in homopolypeptides under stretching.
AB  - We consider the effect of an external applied force on the alpha-helix-coil
      transition of a single-stranded homopolypeptide chain. An annealed scenario is
      assumed, where the building amino acid monomers may interconvert between random
      coiled and ordered alpha-helical configurations. By exact evaluation of the
      partition function of the freely jointed chain with helix-coil internal degrees
      of freedom in the thermodynamic limit, we obtain the result that the stress
      strain characteristic has an asymmetrical sigmoid shape with a prominent
      pseudoplateau. Because of the one-dimensional nature of this system, fluctuations
      dominate over the mean-field approximation, which incorrectly predicts a second
      order phase transition.

PMID- 11308521
TI  - Field theory for reaction-diffusion processes with hard-core particles.
AB  - We show how to build up a systematic bosonic field theory for a general reaction
      diffusion process involving hard-core particles in arbitrary dimension. We
      discuss a recent approach proposed by Park, Kim, and Park [Phys. Rev. E 62, 7642
      (2000)]. As a test bench for our method, we show how to recover the equivalence
      between asymmetric diffusion of excluding particles and the noisy Burgers
      equation.

PMID- 11308522
TI  - Car accidents on a single-lane highway.
AB  - We study the occurrence of car accidents in the Nagel-Schreckenberg model. Both
      the effects of stochastic braking and speed limit are analyzed. An approximate
      scaling relation is observed with the varying of speed limit. The stochastic
      noise will enhance the probability for accidents in the low density region and
      suppress that in the high density region. The probability for car accidents to
      occur becomes a broadened distribution over a wide range of density.

PMID- 11308523
TI  - Insight in shear banding under transient flow.
AB  - The rheo-optical behavior of a viscoelastic solution of a surfactant subjected to
      transient shear flows is reported. A steplike shear rate is suddenly imposed and
      we record the transient physical characteristics of the liquid, i.e., the shear
      stress sigma, the transmitted intensity I(t), and the scattering pattern. At the
      inception of the flow the shear stress shows an important overshoot followed by
      damped oscillations which also appear in the intensity profile. Then a sigmoidal
      relaxation process brings the liquid in its final steady state. During this first
      phase, the diffusion pattern due to enhanced concentration fluctuations can also
      be observed. A fine anisotropic layer appears near the moving wall shortly after
      the inception of the flow, but its width starts to increase significantly well
      after the end of the relaxation process. When the laser beam travels through this
      band a diffraction pattern can be observed indicating that it is formed by small
      subbands, the characteristic width of which is in the order of 100 micro m.

PMID- 11308524
TI  - Copolymer-assisted generation of three-dimensional patterns by replicating two
      dimensional substrate motifs.
AB  - We use a three-dimensional self-consistent field model to study copolymer
      adsorption from polymer melts onto chemically heterogeneous substrates. We show
      that in situations where the copolymer sequence distribution is commensurate with
      the spatial distribution of the substrate chemical impurities, the two
      dimensional substrate pattern gets transcribed into three dimensions and
      propagates into the polymer mixture. This transference scheme can assist in
      designing nanostructures that find use in various areas of science and
      technology.

PMID- 11308525
TI  - Comment on "surface restructuring, kinetic oscillations, and chaos in
      heterogeneous catalytic reactions".
AB  - In a recent article Zhdanov studied the oscillating NO+H2 reaction on the Pt(100)
      single-crystal surface [V. P. Zhdanov, Phys. Rev. E 59, 6292 (1999)]. We have
      scrutinized his model and found fundamental errors in the chemical modeling, in
      the modeling of the surface reconstruction and in the simulation procedure
      itself.

PMID- 11308526
TI  - Reply to "Comment on 'Surface restructuring, kinetic oscillations, and chaos in
      heterogeneous catalytic reactions' ".
AB  - In my numeration, the criticism of my simulations of kinetic oscillations in NO
      reduction by H2 on Pt(100) [V. P. Zhdanov, Phys. Rev. E 59, 6292 (1999)] by
      Kuzovkov, Kortluke, and von Niessen [preceding paper, Phys. Rev. 63, 023101
      (2001)] contains 19 comments. I show that four comments are irrelevant. The other
      15 comments are wrong, because they either contradict the basic principles of the
      theory of phase transitions, Monte Carlo simulations, and catalytic chemistry or
      ignore numerous experimental data on adsorbate-induced restructuring of the
      Pt(100) surface.

PMID- 11308527
TI  - Effect of the accelerating growth of communications networks on their structure.
AB  - Motivated by data on the evolution of the Internet and World Wide Web we consider
      scenarios of self-organization of nonlinearly growing networks into free-scale
      structures. We find that the accelerating growth of networks establishes their
      structure. For growing networks with preferential linking and increasing density
      of links, two scenarios are possible. In one of them, the value of the exponent
      gamma of the distribution of the number of incoming links is between 3/2 and 2.
      In the other scenario, gamma>2 and the distribution is necessarily nonstationary.

PMID- 11308528
TI  - Experimental evidence of tunneling as a stochastic process.
AB  - A model for tunneling based on stochastic processes proves to be capable of
      interpreting the results of two experiments at the microwave scale. The first of
      these consisted of measuring the penetration time in a subcutoff waveguide; the
      second one, in measuring the shift of a beam in a frustrated total reflection.
      Said shift which is a measurement of the traversal time of the barrier. In both
      cases, a peak in the real-time component was evidenced, as predicted by the
      theoretical model.

PMID- 11308529
TI  - Transport on directed percolation clusters.
AB  - We study random lattice networks consisting of resistorlike and diodelike bonds.
      For investigating the transport properties of these random resistor diode
      networks we introduce a field-theoretic Hamiltonian amenable to renormalization
      group analysis. We focus on the average two-port resistance at the transition
      from the nonpercolating to the directed percolating phase and calculate the
      corresponding resistance exponent straight phi to two-loop order. Moreover, we
      determine the backbone dimension D(B) of directed percolation clusters to two
      loop order. We obtain a scaling relation for D(B) that is in agreement with well
      known scaling arguments.

PMID- 11308530
TI  - Failure regimes in (1+1) dimensions in fibrous materials.
AB  - In this paper, we introduce a model for fracture in fibrous materials that takes
      into account the rupture height of the fibers, in contrast with previous models.
      Thus, we obtain the profile of the fracture and calculate its roughness, defined
      as the variance around the mean height. We investigate the relationship between
      the fracture roughness and the fracture toughness.

PMID- 11308531
TI  - Anomalous scaling of velocity and temperature structure functions.
AB  - Scaling-range power-law exponents of velocity and temperature structure functions
      are examined through the dimensional analysis framework of the refined similarity
      hypotheses using measurements in a variety of turbulent flows and Reynolds
      numbers. The resulting magnitude of the scaling exponent associated with the
      locally averaged energy dissipation rate epsilon(r) is always larger than 2/3,
      whereas the exponent for the locally averaged temperature dissipation rate chi(r)
      is always smaller than 2/3. While the epsilon(r) exponent may be reconciled with
      the exponent of the velocity structure function, the distributions of the chi(r)
      and temperature structure function exponents are inherently different.

PMID- 11308532
TI  - Probability density function and "plus" and "minus" structure functions in a
      turbulent channel flow.
AB  - We consider the statistical properties of the longitudinal velocity increments in
      a turbulent channel flow at different distances from the wall. The probability
      density function (PDF) of the velocity difference of the streamwise component
      near the wall are found to be, especially at small scales, strongly skewed,
      showing a very long left tail. We consider "plus" and "minus" structure functions
      and compute separately the statistics for the right and left part of the PDF. It
      is found that the relative scaling exponents for the right tail are less affected
      by the presence of the wall and their values are consistent with the ones found
      in experiments in homogeneous and isotropic turbulence. A simple phenomenological
      model that explains the results obtained is also given.

PMID- 11308533
TI  - Anomalous exponents to order epsilon 3 in the rapid-change model of passive
      scalar advection.
AB  - Field-theoretic renormalization group is applied to the Kraichnan model of a
      passive scalar advected by the Gaussian velocity field with the covariance
      <v(t,x)v(t('),x)>-<v(t,x)v(t('),x('))>~delta(t-t('))|x-x(')|(epsilon). Inertial
      range anomalous exponents, related to the scaling dimensions of tensor composite
      operators built of the scalar gradients, are calculated to the order epsilon(3)
      of the epsilon expansion. The nature and the convergence of the epsilon expansion
      in the models of turbulence are briefly discussed.

PMID- 11308534
TI  - Long-range attractive and repulsive forces in a two-dimensional complex (dusty)
      plasma.
AB  - An interaction of a negatively biased wire with a monolayer lattice of negatively
      charged particles has been studied experimentally. The particles levitated at the
      height of the wire in a sheath of an rf discharge. It was found that the
      particles close to the wire were repelled from it electrostatically, while the
      far particles were attracted due to the drag of the ion flow deflected toward the
      wire. The ion drag force prevails far from the wire, whereas the electrostatic
      force is stronger close to the wire. The range of the forces is one to two orders
      of magnitude greater than the screening length.

PMID- 11308535
TI  - Statistics of soliton-bearing systems with additive noise.
AB  - We present a consistent method to calculate the probability distribution of
      soliton parameters in systems with additive noise. Even though the noise is weak,
      we are interested in probabilities of large fluctuations (generally non-Gaussian)
      which are beyond perturbation theory. Our method is a development of the
      instanton formalism (method of optimal fluctuation) based on a saddle-point
      approximation in the path integral. We first solve a fundamental problem of
      soliton statistics governed by a noisy nonlinear Schrodinger equation. We then
      apply our method to optical soliton transmission systems using signal control
      elements (filters and amplitude and phase modulators).

PMID- 11308536
TI  - Resonant suppression of Turing patterns by periodic illumination.
AB  - We study the resonant behavior of Turing pattern suppression in a model of the
      chlorine dioxide-iodine-malonic acid reaction with periodic illumination. The
      results of simulations based on integration of partial differential equations
      display resonance at the frequency of autonomous oscillations in the
      corresponding well stirred system. The resonance in Turing pattern suppression is
      sharper at lower complexing agent concentration and is affected by the waveform
      of the periodic driving force. Square wave (on-off) periodic forcing is more
      effective in suppressing Turing patterns than sinusoidal forcing. We compare the
      dynamics of periodically forced Turing patterns with the dynamics of periodically
      forced nonhomogeneous states in a system of two identical coupled cells.
      Bifurcation analysis based on numerical continuation of the latter system gives
      good predictions for the boundaries of the major resonance regions of the
      periodically forced patterns.

PMID- 11308537
TI  - Classical phase space and statistical mechanics of identical particles.
AB  - Starting from the quantum theory of identical particles, we show how to define a
      classical mechanics that retains information about the quantum statistics. We
      consider two examples of relevance for the quantum Hall effect: identical
      particles in the lowest Landau level, and vortices in the Chern-Simons Ginzburg
      Landau model. In both cases the resulting classical statistical mechanics is
      shown to be a nontrivial classical limit of Haldane's exclusion statistics.

PMID- 11308538
TI  - Scaling behavior for finite O(n) systems with long-range interaction.
AB  - A detailed investigation of the scaling properties of the fully finite O(n)
      systems, under periodic boundary conditions, with long-range interaction,
      decaying algebraically with the interparticle distance r like r(-d-sigma), below
      their upper critical dimension, is presented. The computation of the scaling
      functions is done to one loop order in the nonzero modes. The results are
      obtained in an expansion of powers of sqrt[epsilon], where epsilon=2sigma-d up to
      O(epsilon(3/2)). The thermodynamic functions are found to depend upon the scaling
      variable z=RU(-1/2)L(2-eta-epsilon/2), where R and U are the coupling constants
      of the constructed effective theory, and L is the linear size of the system. Some
      simple universal results are obtained.

PMID- 11308539
TI  - Unexpected transient effect.
AB  - When a grooved periodic profile cut in a crystalline surface relaxes through
      surface diffusion, flatter parts appear at the top and bottom in the transient
      state which precedes complete smoothing. This has been attributed to a tendency
      of successive steps of identical sign to draw closer to one another. This kind of
      kinetic interaction is a consequence of the finite value of the interatomic
      distance, and is present even if no interaction between steps is taken into
      account. We investigate this effect in a very simplified model, namely, a one
      dimensional profile with alternating pairs of up and down steps, where no
      annihilation of steps is allowed. The quantitative effect is partly treated
      analytically.

PMID- 11308540
TI  - Criticality in a model with absorbing states.
AB  - We study a one-dimensional model that undergoes a transition between an active
      and an absorbing phase. Monte Carlo simulations supported by some additional
      arguments prompted us to predict the exact location of the critical point and
      critical exponents in this model. The exponents delta=0.5 and z=2 follows from
      random-walk-type arguments. The exponents beta=nu( perpendicular) are found to be
      nonuniversal and encoded in the singular part of reactivation probability, as
      recently discussed by H. Hinrichsen (cond-mat/0008179). A related model with
      quenched randomness is also studied.

PMID- 11308541
TI  - Hysteresis effects in spin systems with quenched disorder.
AB  - We present detailed numerical results for hysteresis effects in spin-glass
      systems. In particular, we focus on the dependence of hysteresis loop area on (a)
      disorder amplitude and (b) frequency of the applied magnetic field.

PMID- 11308542
TI  - Ising model on nonorientable surfaces: exact solution for the Mobius strip and
      the Klein bottle.
AB  - Closed-form expressions are obtained for the partition function of the Ising
      model on an MxN simple-quartic lattice embedded on a Mobius strip and a Klein
      bottle. The solutions all lead to the same bulk free energy, but for finite M and
      N the expressions are different depending on whether the strip width M is odd or
      even. Finite-size corrections at criticality are analyzed and compared with those
      under cylindrical and toroidal boundary conditions. Our results are consistent
      with the conformal field prediction of a central charge c=1/2, provided that the
      twisted Mobius boundary condition is regarded as a free or fixed boundary.

PMID- 11308543
TI  - Coexistence curve exponent of a binary mixture with a high molecular weight
      polymer.
AB  - We studied the effects of a high molecular weight polymer (polyacrylic acid, PAA,
      M(w)=7.5 x 10(5)) on the coexistence curve of a binary liquid mixture (2,6
      lutidine + water, LW). A high precision refractometer was built to measure the
      temperature dependence of the refractive indexes of the two coexisting phases of
      phase separated LW samples containing less than 1 mg/cc of PAA. From the
      refractive indexes we mapped out the coexistence curve and obtained the
      refractive index difference triangle upn between the two coexisting phases. At
      temperature T close to the critical temperature T(c), the critical exponent beta
      such that triangle n inversely proportional to (T-T(c))(beta) was found to be
      0.41+/-0.02 which is higher than (0.31+/-0.01) that of pure LW.

PMID- 11308544
TI  - Long-time behavior of the velocity autocorrelation function for moderately dense,
      soft-repulsive, and Lennard-Jones fluids.
AB  - The long-time behavior of the velocity autocorrelation function (VAF), for hard
      disk and sphere systems, has been extensively explored. Its behavior for systems
      interacting via a soft repulsive or attractive potential is less well known. We
      explore the conditions under which the nonexponential, long-time tail in the
      velocity autocorrelation function of a tagged atom, in soft-repulsive sphere
      (Weeks-Chandler-Andersen) and Lennard-Jones atomic fluids, may be readily
      observed by the molecular dynamics method. The effect of changing the system
      size, the fluid density, the form of the interatomic force and the mass of the
      tagged atoms are investigated. We were able to observe this long-time tail only
      for systems of moderate density. At low density the effect, if it exists, is at
      longer times than we can currently simulate owing to limitations of system size
      and at higher densities these tails were not observed possibly due to other
      effects dominating the behavior of the VAF and masking this behavior. Under the
      physical conditions that are simulated here attractive forces have very little
      effect on the behavior of the VAF. However, as the mass of the tagged particles
      is increased the time at which the long-time tail commences is lengthened and its
      magnitude is significantly increased. This later effect suggests that by
      increasing the mass of the tagged particles one may be able to study more readily
      the behavior, nature and physical origin of long-time behavior of the VAF both by
      computational and by experimental techniques.

PMID- 11308545
TI  - Glass transition of a particle in a random potential, front selection in
      nonlinear renormalization group, and entropic phenomena in Liouville and sinh
      Gordon models.
AB  - We study via renormalization group (RG), numerics, exact bounds, and qualitative
      arguments the equilibrium Gibbs measure of a particle in a d-dimensional Gaussian
      random potential with translationally invariant logarithmic spatial correlations.
      We show that for any d>/=1 it exhibits a transition at T=T(c)>0. The low
      temperature glass phase has a nontrivial structure, being dominated by a few
      distant states (with replica symmetry breaking phenomenology). In finite
      dimension this transition exists only in this "marginal glass" case (energy
      fluctuation exponent straight theta=0) and disappears if correlations grow faster
      (single ground-state dominance straight theta>0) or slower (high-temperature
      phase). The associated extremal statistics problem for correlated energy
      landscapes exhibits universal features which we describe using a nonlinear
      Kolmogorov (KPP) RG equation. These include the tails of the distribution of the
      minimal energy (or free energy) and the finite-size corrections, which are
      universal. The glass transition is closely related to Derrida's random energy
      models. In d=2, the connection between this problem and Liouville and sinh-Gordon
      models is discussed. The glass transition of the particle exhibits interesting
      similarities with the weak- to strong-coupling transition in Liouville (c=1
      barrier) and with a transition that we conjecture for the sinh-Gordon model, with
      correspondence in some exact results and RG analysis. Glassy freezing of the
      particle is associated with the generation under RG of new local operators and of
      nonsmooth configurations in Liouville. Applications to Dirac fermions in random
      magnetic fields at criticality reveal a peculiar "quasilocalized" regime
      (corresponding to the glass phase for the particle), where eigenfunctions are
      concentrated over a finite number of distant regions, and allow us to recover the
      multifractal spectrum in the delocalized regime.

PMID- 11308546
TI  - Exact solution of a stochastic directed sandpile model.
AB  - We introduce and analytically solve a directed sandpile model with stochastic
      toppling rules. The model clearly belongs to a different universality class from
      its counterpart with deterministic toppling rules, previously solved by Dhar and
      Ramaswamy. The critical exponents are D(//)=7/4, tau=10/7 in two dimensions and
      D(//)=3/2, tau=4/3 in one dimension. The upper critical dimension of the model is
      three, at which the exponents apart from logarithmic corrections reach their mean
      field values D(//)=2, tau=3/2.

PMID- 11308547
TI  - Basins of attraction on random topography.
AB  - We investigate the consequences of fluid flowing on a continuous surface upon the
      geometric and statistical distribution of the flow. We find that the ability of a
      surface to collect water by its mere geometrical shape is proportional to the
      curvature of the contour line divided by the local slope. Consequently, rivers
      tend to lie in locations of high curvature and flat slopes. Gaussian surfaces are
      introduced as a model of random topography. For Gaussian surfaces the relation
      between convergence and slope is obtained analytically. The convergence of flow
      lines correlates positively with drainage area, so that lower slopes are
      associated with larger basins. As a consequence, we explain the observed relation
      between the local slope of a landscape and the area of the drainage basin
      geometrically. To some extent, the slope-area relation comes about not because of
      fluvial erosion of the landscape, but because of the way rivers choose their
      path. Our results are supported by numerically generated surfaces as well as by
      real landscapes.

PMID- 11308548
TI  - Creep motion in a random-field Ising model.
AB  - We analyze numerically a moving interface in the random-field Ising model which
      is driven by a magnetic field. Without thermal fluctuations the system displays a
      depinning phase transition, i.e., the interface is pinned below a certain
      critical value of the driving field. For finite temperatures the interface moves
      even for driving fields below the critical value. In this so-called creep regime
      the dependence of the interface velocity on the temperature is expected to obey
      an Arrhenius law. We investigate the details of this Arrhenius behavior in two
      and three dimensions and compare our results with predictions obtained from
      renormalization group approaches.

PMID- 11308549
TI  - Relaxation in kinetic models on alternating linear chains.
AB  - A restricted dynamics, previously introduced in a kinetic model for relaxation
      phenomena in linear polymer chains, is used to study the dynamic critical
      exponent of one-dimensional Ising models. Both an alternating isotopic chain and
      an alternating-bond chain are considered. In contrast with what occurs for
      Glauber dynamics, in these two models the dynamic critical exponent turns out to
      be the same. The alternating isotopic chain with the restricted dynamics is shown
      to lead to Nagel scaling for temperatures above some critical value. Further
      support is given relating the Nagel scaling to the existence of multiple
      (simultaneous) relaxation processes, the dynamics apparently not playing the most
      important role in determining such scaling.

PMID- 11308550
TI  - Percolation, Bose-Einstein condensation, and string proliferation.
AB  - The close analogy between cluster percolation and string proliferation in the
      context of critical phenomena is studied. Like clusters in percolation theory,
      closed strings, which can be either finite-temperature worldlines or topological
      line defects, are described by a distribution parametrized by only two exponents.
      On approaching the critical point, the string tension vanishes and the loops
      proliferate, thereby signalling the onset of Bose-Einstein condensation (in the
      case of worldlines) or the disordering of the ordered state (in the case of
      vortices). The ideal Bose gas with modified energy spectrum is used as a stepping
      stone to derive general expressions for the critical exponents in terms of the
      two exponents parametrizing the loop distribution near criticality.

PMID- 11308551
TI  - Exactly solved dynamics for an infinite-range spin system.
AB  - It is well known that the dynamical evolution of a system of N spins can be
      viewed as a walk along the edges of an N-dimensional hypercube. I use this
      correspondence in an infinite-range spin system to derive a diffusion equation
      for the magnetization. The diffusion equation then leads to an ordinary
      differential equation that describes the time evolution of the magnetization for
      any given initial condition, and it is used to derive both static and dynamic
      properties of the spin system.

PMID- 11308552
TI  - Synchronization regimes in coupled noisy excitable systems.
AB  - We study synchronization regimes in a system of two coupled noisy excitable
      systems which exhibit excitability close to an Andronov bifurcation. The
      uncoupled system possesses three fixed points: a node, a saddle, and an unstable
      focus. We demonstrate that with an increase of coupling strength the system
      undergoes transitions from a desynchronous state to a train synchronization
      regime to a phase synchronization regime, and then to a complete synchronization
      regime. Train synchronization is a consequence of the existence of a saddle in
      the phase space. The mechanism of transitions in coupled noisy excitable systems
      is different from that in coupled phase-coherent chaotic systems.

PMID- 11308553
TI  - On-line adaptive chaotic demodulator based on radial-basis-function neural
      networks.
AB  - Chaotic modulation is a useful technique for spread spectrum communication. In
      this paper, an on-line adaptive chaotic demodulator based on a radial-basis
      function (RBF) neural network is proposed and designed. The demodulator is
      implemented by an on-line adaptive learning algorithm, which takes advantage of
      the good approximation capability of the RBF network and the tracking ability of
      the extended Kalman filter. It is demonstrated that, provided the modulating
      parameter varies slowly, spread spectrum signals contaminated by additive white
      Gaussian noise in a channel can be tracked in a time window, and the modulating
      parameter, which carries useful messages, can be estimated using the least-square
      fit. The Henon map is chosen as the chaos generator. Four test message signals,
      namely, square-wave, sine-wave, speech and image signals, are used to evaluate
      the performance. The results verify the ability of the demodulator in tracking
      the dynamics of the chaotic carrier as well as retrieving the message signal from
      a noisy channel.

PMID- 11308554
TI  - Numerical study of Lyapunov exponents for products of correlated random matrices.
AB  - We numerically study Lyapunov spectra and the maximal Lyapunov exponent (MLE) in
      products of real symplectic correlated random matrices, each of which is
      generated by a modified Bernoulli map. We can systematically investigate the
      influence of the correlation on the Lyapunov exponents because the statistical
      properties of the sequence generated by the map, whose correlation function shows
      power-law decay, have been well investigated. It is shown that the form of the
      scaled Lyapunov spectra does not change much even if the correlation of the
      sequence increases in the stationary region, and in the nonstationary region the
      forms are quite different from those obtained in the delta-correlated purely
      random case. The fluctuation strength dependence of the MLE changes with
      increasing correlation, and a different scaling law from that of the delta
      correlated case can be observed in the nonstationary region. Moreover, the
      statistical properties of the probability distribution of the local Lyapunov
      exponents are quite different from those obtained from delta-correlated random
      matrices. Slower convergence that does not obey the central-limit theorem is
      observed for increasing correlation.

PMID- 11308555
TI  - Spectral statistics of the two-body random ensemble revisited.
AB  - Using longer spectra we reanalyze spectral properties of the two-body random
      ensemble studied 30 years ago. At the center of the spectra the old results are
      largely confirmed, and we show that the nonergodicity is essentially due to the
      variance of the lowest moments of the spectra. The longer spectra allow us to
      test and reach the limits of validity of French's correction for the number
      variance. At the edge of the spectra we discuss the problems of unfolding in more
      detail. With a Gaussian unfolding of each spectrum the nearest-neighbor spacing
      distribution between ground state and first exited state is shown to be stable.
      Using such an unfolding the distribution tends toward a semi-Poisson distribution
      for longer spectra. For comparison with the nuclear table ensemble we could use
      such unfolding obtaining similar results as in the early papers, but an ensemble
      with realistic splitting gives reasonable results if we just normalize the
      spacings in accordance with the procedure used for the data.

PMID- 11308556
TI  - Diffusion with rearranging traps.
AB  - A model for diffusion on a cubic lattice with a random distribution of traps is
      developed. The traps are redistributed at certain time intervals. Such models are
      useful for describing systems showing dynamic disorder, such as ion-conducting
      polymers. In the present model the traps are infinite, unlike an earlier version
      with finite traps. For the infinite trap version a simple analytical calculation
      is possible and the results agree qualitatively with simulations.

PMID- 11308557
TI  - Spectral properties of a mixed system using an acoustical resonator.
AB  - We experimentally study the spectral properties of a mixed system using the
      flexural modes of a clover shaped plate. The system is called mixed because the
      corresponding ray dynamics has both chaotic and integrable regions in its phase
      space. The eigenvalue statistics show intermediate properties between the
      universal statistics corresponding to chaotic geometries which show Gaussian
      orthogonal ensemble statistics and integrable geometries that show Poisson
      statistics. We further investigate the Fourier transform of the peaks to study
      the influence of the length scales of the plate on the properties of the acoustic
      resonances. We observe a weak signal of the periodic orbits in the experimental
      data. Although some of the peaks in the Fourier transform of the eigenvalue
      spectrum correspond to the shortest stable periodic orbits, other strong peaks
      are also observed. To understand the role of symmetries, we start with a clover
      shaped plate belonging to the C(4v) point symmetry group, and progressively
      reduce the symmetry by sanding one of the edges. A Shnirelman peak in P(s) is
      observed for the highly symmetric situation due to level clustering.

PMID- 11308558
TI  - Response function of an irregular oscillator.
AB  - Properties of the response functions for a two-dimensional quartic oscillator are
      studied based on the diagonalization of the Hamiltonian in a large model space.
      In particular, response functions corresponding to a given momentum transfer are
      studied for different values of the coupling parameter in the Hamiltonian. The
      latter controls regular or chaotic nature of the spectra and eigenstates of the
      system. Fluctuation properties of the energy-strength correlation of the response
      are investigated. Even when the statistical properties of the system indicate an
      almost completely chaotic character, there remains a typical structure in the
      response function similar to that in the regular system. The nature of this
      structure is studied in some detail.

PMID- 11308559
TI  - Scarred patterns in surface waves.
AB  - Surface wave patterns are investigated experimentally in a system geometry that
      has become a paradigm of quantum chaos: the stadium billiard. Linear waves in
      bounded geometries for which classical ray trajectories are chaotic are known to
      give rise to scarred patterns. Here, we utilize parametrically forced surface
      waves (Faraday waves), which become progressively nonlinear beyond the wave
      instability threshold, to investigate the subtle interplay between boundaries and
      nonlinearity. Only a subset (three main types) of the computed linear modes of
      the stadium are observed in a systematic scan. These correspond to modes in which
      the wave amplitudes are strongly enhanced along paths corresponding to certain
      periodic ray orbits. Many other modes are found to be suppressed, in general
      agreement with a prediction by Agam and Altshuler based on boundary dissipation
      and the Lyapunov exponent of the associated orbit. Spatially asymmetric or
      disordered (but time-independent) patterns are also found even near onset. As the
      driving acceleration is increased, the time-independent scarred patterns persist,
      but in some cases transitions between modes are noted. The onset of
      spatiotemporal chaos at higher forcing amplitude often involves a nonperiodic
      oscillation between spatially ordered and disordered states. We characterize this
      phenomenon using the concept of pattern entropy. The rate of change of the
      patterns is found to be reduced as the state passes temporarily near the ordered
      configurations of lower entropy. We also report complex but highly symmetric
      (time-independent) patterns far above onset in the regime that is normally
      chaotic.

PMID- 11308560
TI  - Chaos, ergodic convergence, and fractal instability for a thermostated canonical
      harmonic oscillator.
AB  - The authors thermostat a qp harmonic oscillator using the two additional control
      variables zeta and xi to simulate Gibbs' canonical distribution. In contrast to
      the motion of purely Hamiltonian systems, the thermostated oscillator motion is
      completely ergodic, covering the full four-dimensional [q,p,zeta,xi] phase space.
      The local Lyapunov spectrum (instantaneous growth rates of a comoving corotating
      phase-space hypersphere) exhibits singularities like those found earlier for
      Hamiltonian chaos, reinforcing the notion that chaos requires kinetic-as opposed
      to statistical-study, both at and away from equilibrium. The exponent
      singularities appear to have a fractal character.

PMID- 11308561
TI  - Chaos-nonchaos phase transitions induced by external noise in ensembles of
      nonlinearly coupled oscillators.
AB  - Nonlinear dynamical behaviors of ensembles of nonlinearly coupled oscillators
      subjected to external noise are studied on the basis of nonlinear Fokker-Planck
      equations. The effects of two kinds of noise, the Langevin noise and the noise
      introduced in the coupling strength, are investigated, and phase transitions
      involving chaos-nonchaos bifurcations are found to occur as the noise level is
      changed. An H theorem is proposed for the nonlinear Fokker-Planck equation to
      ensure stability of the Gaussian type solution that is approached for large
      times.

PMID- 11308562
TI  - Partial synchronization and spontaneous spatial ordering in coupled chaotic
      systems.
AB  - A model of many symmetrically and locally coupled chaotic oscillators is studied.
      Partial chaotic synchronizations associated with spontaneous spatial ordering are
      demonstrated. Very rich patterns of the system are revealed, based on partial
      synchronization analysis. The stabilities of different partially synchronous
      spatiotemporal structures and some dynamical behaviors of these states are
      discussed both numerically and analytically.

PMID- 11308563
TI  - Stability and bifurcations of periodically modulated, optically injected laser
      diodes.
AB  - Recent experiments using lasers subject to external injection [T. B. Simpson,
      Opt. Commun., 170, 93 (1999)] have shown remarkable locking performances when a
      small reference current modulation is added to the dc-bias current. The locking
      problem is studied analytically by using a multiple scale perturbation method. We
      derive a slow time amplitude equation for the laser rapid limit-cycle
      oscillations. The solution of this equation is then investigated both
      analytically and numerically using a continuation method. We find that the
      intensity of the laser field can be time periodic (locking) or quasiperiodic
      (unlocking) and that there exist two distinct bifurcation mechanisms leading to
      locking. Finally, we compare bifurcation diagrams based on our amplitude equation
      with diagrams obtained from the laser original equations and find a good
      quantitative agreement.

PMID- 11308564
TI  - Transition to phase synchronization in coupled periodically driven chaotic
      pendulums.
AB  - We have studied the transition to phase synchronization in the system of two
      coupled periodically driven pendulums. For the case of identical units, the
      coupled system has an infinite number of invariant subspaces. The synchronization
      desynchronization transition is at the blowout bifurcation which coincides with
      the hyperchaos-chaos transition. On-off intermittency and intermingled basins of
      attraction can be observed close to this transition. For the case of nonidentical
      pendulums, the synchronization-desynchronization transition occurs far beyond the
      hyperchaos-chaos transition. The basin structure and the statistics of the
      accompanying intermittency are different from those for identical units.

PMID- 11308565
TI  - Spatiotemporal patterns and symmetry breaking on a ring electrode.
AB  - A series of experiments on a ring electrode with changes in a parameter, the
      applied potential, are described. Spatiotemporal patterns are investigated in a
      region of parameter space in which relaxation oscillations occur. The simplest
      state is a period 2Pi oscillation that has full O(2) symmetry so that at each
      instant the pattern is unchanged by rotations or reflections of the ring. With
      change in parameter a spatiotemporal period doubling occurs to period 4Pi. This
      is followed by a symmetry breaking to another state with period 4Pi and
      subsequently by a second period doubling to period 8Pi. Proper orthogonal
      decomposition is used as an aid in elucidating the nature of the transitions.

PMID- 11308566
TI  - Stochastic multiresonance in a chaotic map with fractal basins of attraction.
AB  - Noise-free stochastic resonance in a chaotic kicked spin model at the edge of the
      attractor merging crisis is considered. The output signal reflects the occurrence
      of crisis-induced jumps between the two parts of the attractor. As the control
      parameter-the amplitude of the magnetic field pulses-is varied, the signal-to
      noise ratio shows plateaus and multiple maxima, thus stochastic multiresonance is
      observed. It is shown that the multiresonance occurs due to a fractal structure
      of the precritical attractors and their basins. In the adiabatic approximation
      theoretical expression for the signal-to-noise ratio is derived, based on the
      theory of oscillations in average crisis-induced transient lifetimes. Numerical
      and theoretical results agree quantitatively just above the threshold for crisis
      and qualitatively in a wide range of the control parameter.

PMID- 11308567
TI  - Nonlinear aspects of analysis and synthesis of speech time series data.
AB  - In this work we study a simple model of voiced sound production. We analyze
      contributions that the qualitative theory of dynamical systems can make to the
      analysis and synthesis of human speech.

PMID- 11308568
TI  - Mechanism for the riddling transition in coupled chaotic systems.
AB  - We investigate the loss of chaos synchronization in coupled chaotic systems
      without symmetry from the point of view of bifurcations of unstable periodic
      orbits embedded in the synchronous chaotic attractor (SCA). A mechanism for
      direct transition to global riddling through a transcritical contact bifurcation
      between a periodic saddle embedded in the SCA and a repeller on the boundary of
      its basin of attraction is thus found. Note that this bifurcation mechanism is
      different from that in coupled chaotic systems with symmetry. After such a
      riddling transition, the basin becomes globally riddled with a dense set of
      repelling tongues leading to divergent orbits. This riddled basin is also
      characterized by divergence and uncertainty exponents, and thus typical power-law
      scaling is found.

PMID- 11308569
TI  - Instability versus nonlinearity in certain nonautonomous oscillators: A critical
      dynamical transition driven by the initial energy.
AB  - The equation of motion q+Omega(2)(t)q+alpha/q/(gamma-2)q=0 (gamma>2) for the real
      coordinate q(t) is studied, as an example of the interplay between nonlinearity
      and instability. Two contrasting mechanisms determine the behavior of q(t), when
      the time-varying frequency Omega(t) does produce exponential instability in the
      linear equation q (lin)+Omega(2)(t)q(lin)=0. At low energy, the exponential
      instability is the dominant effect, while at high energy the bounding effect of
      the autonomous nonlinear term prevails. Starting from low initial energies, the
      result of this competition is a time-varying energy characterized by
      quasiperiodic peaks, with an average recurrence time T(peak). A closed critical
      curve S(omega) exists in the initial phase space, whose crossing corresponds to a
      divergence of the recurrence time T(peak). The divergence of T(peak) has a
      universal character, expressed by a critical exponent a=1. The critical curve
      S(omega) is the initial locus of the solutions that vanish asymptotically. A
      close relationship exists between this dynamical transition and the transition
      from mobile to self-trapped polarons in one spatial dimension. The application to
      a number of physical problems is addressed, with special attention to the Fermi
      Pasta-Ulam problem and to transitions to chaos.

PMID- 11308570
TI  - Interruption of torus doubling bifurcation and genesis of strange nonchaotic
      attractors in a quasiperiodically forced map: mechanisms and their
      characterizations.
AB  - A simple quasiperiodically forced one-dimensional cubic map is shown to exhibit
      very many types of routes to chaos via strange nonchaotic attractors (SNAs) in a
      two-parameter (A-f) space. The routes include transitions to chaos via SNAs from
      both a one-frequency torus and a period-doubled torus. In the former case, we
      identify the fractalization and type-I intermittency routes. In the latter case,
      we point out that at least four distinct routes for the truncation of the torus
      doubling bifurcation and the creation of SNAs occur in this model. In particular,
      the formation of SNAs through Heagy-Hammel, fractalization, and type-III
      intermittent mechanisms is described. In addition, it has been found that in this
      system there are some regions in the parameter space where a dynamics involving a
      sudden expansion of the attractor, which tames the growth of period-doubling
      bifurcation, takes place, creating the SNA. The SNAs created through different
      mechanisms are characterized by the behavior of the Lyapunov exponents and their
      variance, by the estimation of the phase sensitivity exponent, and through the
      distribution of finite-time Lyapunov exponents.

PMID- 11308572
TI  - Transport and entropy production due to chaos or turbulence.
AB  - A projection-operator method is developed for the statistical-mechanical
      formulation of chaotic or turbulent transport, such as chaos-induced friction in
      a forced damped pendulum and turbulent viscosity in a turbulent fluid. Then the
      nonlinear deterministic equations of motion for these dynamical systems are
      transformed into linear stochastic equations with chaotic or turbulent
      fluctuating forces. This leads to a fluctuation-dissipation formula which relates
      the chaotic or turbulent transport coefficients to the time correlation of the
      fluctuating forces. Applying this theory to the forced damped pendulum, we
      explore the chaos-induced friction and the power spectra of chaotic orbits.
      Applying it to the fluid turbulence governed by the Navier-Stokes equation, we
      find that the turbulent viscosity in the inertial subrange depends on wave number
      k as k(-beta) with beta=4 / 3+1 / 2/micro(2/3)/, micro (q) being the
      intermittency exponent of order q.

PMID- 11308571
TI  - Sonoluminescence and phase diagrams of single bubbles at low dissolved air
      concentrations.
AB  - We studied experimentally the dependence of light emission and phase space
      boundaries of air bubbles in water on the level of degassing down to low partial
      pressures of 15 mmHg. We found that the maximum obtainable light intensity
      increased monotonically by lowering the concentration of dissolved air in water.
      We also present a new technique to obtain the acoustic pressure (P(a)) and
      ambient radius (R0) parameters, based on the information provided by the timing
      of the flashes in the acoustic cycle. Using this technique we give phase diagrams
      of the bubble in the (R0,P(a)) and (P(a), gas concentration) space, and discuss
      the parametric dependence of the light intensity. The resulting power-law
      dependence of the relative intensity normalized by the ambient volume of the
      bubble on the expansion ratio indicates that more extreme conditions are
      attainable inside a bubble at dissolved air concentration of 15 mmHg than at 150
      mmHg.

PMID- 11308573
TI  - Body-force effect on the lateral movement of cellular flames at low Lewis
      numbers.
AB  - The body-force effect on the lateral movement of cellular flames is studied by
      unsteady calculations of reactive flows at low Lewis numbers. We employ the
      compressible Navier-Stokes equation including chemical reaction to take account
      of the hydrodynamic effect caused by thermal expansion. A sinusoidal disturbance
      with the linearly most unstable wavelength is superimposed on a plane flame to
      simulate the formation of a cellular flame. The superimposed disturbance grows
      initially with time, and then the flame front changes from a sinusoidal to a
      cellular shape. After the cell formation, the cellular flame moves laterally at
      Lewis numbers lower than unity. The reason is that the diffusive-thermal effect,
      and the nonlinear effect of the flame front, play a primary role in the
      appearance of the lateral movement of cells. The body-force effect has a great
      influence on the lateral velocity of cells. When flames are propagated upward,
      the lateral velocity decreases as the acceleration increases, even though the
      body-force effect has a destabilizing influence. When flames are propagated
      downward, on the other hand, the lateral velocity takes a maximum value at the
      specific acceleration and decreases with an increase in acceleration. The
      dependence of lateral velocity on the acceleration is due to the augmentation and
      diminution in maximum flame temperature and to the broadness and narrowness of a
      high-temperature region behind a convex flame front.

PMID- 11308574
TI  - Dewetting hydrodynamics in 1+1 dimensions.
AB  - A model for the phase transition between partial wetting and dewetting of a
      substrate has been formulated that explicitly incorporates the hydrodynamic flow
      during the dewetting process in 1+1 dimensions. The model simulates a fluid layer
      of finite thickness on a substrate in coexistence with a dry part of the
      substrate and a gas phase above the substrate. Under nonequilibrium "dewetting"
      conditions, the front between the dry part and the wet part of the surface moves
      towards the wet part inducing hydrodynamic flow inside the wet layer. In more
      general terms, the model handles two immiscible fluids with a freely movable
      interface in an inhomogeneous external force field. Handling the interface by a
      new variant of the phase-field model, we obtain an efficient code with well
      defined interfacial properties. In particular, the (free) energy can be chosen at
      will. We demonstrate that our model works well in the viscosity range of creeping
      flow and we give qualitative results for the higher Reynolds numbers. Connections
      to experimental realizations are discussed.

PMID- 11308575
TI  - Scaling hypothesis leading to extended self-similarity in turbulence.
AB  - A scaling hypothesis leading to extended self-similarity (ESS) for structure
      functions (the qth order moments of the magnitude of the longitudinal component
      velocity differences) in isotropic, homogeneous turbulence is proposed. This is
      done by generalizing the scale variable r to rg(r/L), with a crossover function
      g. By extending the refined self-similarity, it is shown that the presented
      scaling also leads to ESS for structure functions of the energy dissipation rate
      fluctuations, and to ESS bridging relations between velocity and dissipation rate
      moments. Extended self-similarity on the basis of a universal crossover function
      g strictly holds toward the outer scale (L) range only. Yet we find at least
      approximate ESS toward the viscous, inner scale (l) range. Furthermore, the
      probability densities for the velocity differences and the energy dissipation
      rate fluctuations which are compatible with this ESS are offered.

PMID- 11308576
TI  - Charge transport measurement during turbulent electroconvection.
AB  - We report measurements of the energy dissipation during electroconvection of a
      nematic liquid crystal in the fully turbulent regime. The energy dissipation is
      quantified by measuring the electric current at constant potential difference. In
      certain cases, we observe the surprising result that the dimensionless energy
      dissipation ceases to increase with increasing potential difference. In some
      circumstances, a power-law scaling relationship between the dimensionless excess
      energy dissipation and the reduced voltage is observed, but the exponent in this
      relationship varies dramatically with both the time scale of the driving electric
      field and the separation between the electrodes.

PMID- 11308577
TI  - Mean-field approximation and a small parameter in turbulence theory.
AB  - Numerical and physical experiments on two-dimensional (2D) turbulence show that
      the differences of transverse components of velocity field are well described by
      Gaussian statistics and Kolmogorov scaling exponents. In this case the
      dissipation fluctuations are irrelevant in the limit of small viscosity. In
      general, one can assume the existence of a critical space dimensionality d=d(c),
      at which the energy flux and all odd-order moments of velocity difference change
      sign and the dissipation fluctuations become dynamically unimportant. At d<d(c)
      the flow can be described by the "mean-field theory," leading to the observed
      Gaussian statistics and Kolmogorov scaling of transverse velocity differences. It
      is shown that in the vicinity of d=d(c) the ratio of the relaxation and
      translation characteristic times decreases to zero, thus giving rise to a small
      parameter of the theory. The expressions for pressure and dissipation
      contributions to the exact equation for the generating function of transverse
      velocity differences are derived in the vicinity of d=d(c). The resulting
      equation describes experimental data on two-dimensional turbulence and
      demonstrates the onset of intermittency as d-d(c)>0 and r/L-->0 in three
      dimensional flows in close agreement with experimental data. In addition, some
      exact relations between correlation functions of velocity differences are
      derived. It is also predicted that the single-point probability density function
      of transverse velocity components in developing as well as in the large-scale
      stabilized two-dimensional turbulence is a Gaussian.

PMID- 11308578
TI  - Solution of functional equations and reduction of dimension in the local energy
      transfer theory of incompressible, three-dimensional turbulence.
AB  - It is shown that the set of integrodifferential and algebraic functional
      equations of the local energy transfer theory may be considerably reduced in
      dimension for the case of isotropic turbulence. This is achieved without
      restricting the solution space. The basis for this is a complete analytical
      solution to the functional equations Q(k;t,t('))=H(k;t,t('))Q(k;t('),t(')) and
      H(k;t,s)H(k;s,t('))=H(k;t,t(')). The solution is proved to depend only on a
      single function straight phi(k;t) solely determining Q and H. Hence the dimension
      of both the dependent and the independent variables is reduced by one. From the
      latter, the corresponding two integrodifferential equations are lowered to a
      single integrodifferential equation for straight phi(k;t), extended by an
      integral side condition on the k dependence of straight phi(k;t). In the limit nu
      ->0, a partial solution to the reduced set of equations is presented in the
      Appendix.

PMID- 11308579
TI  - Nonlocal thermodynamic equilibrium self-consistent average-atom model for plasma
      physics.
AB  - A time-dependent collisional-radiative average-atom model is presented to study
      statistical properties of highly charged ion plasmas in off-equilibrium
      conditions. The time evolution of electron populations and the electron
      covariance matrix is obtained as approximate solutions of a master equation.
      Atomic structure is described either with a screened-hydrogenic model including l
      splitting, or by calculating one-electron states in a self-consistent average
      atom potential. Collisional and radiative excitation/deexcitation and
      ionization/recombination rates, as well as autoionization and dielectronic
      recombination rates, are formulated within the average-configuration framework.
      Local thermodynamic equilibrium is obtained as a specific steady-state solution.
      The influence of atomic structure and the role of autoionization and dielectronic
      recombination processes are studied by calculating steady-state average
      ionization and ionization variance of hot plasmas with or without radiation
      field.

PMID- 11308580
TI  - Experimental study of harmonic generation from solid surfaces irradiated by
      multipicosecond laser pulses.
AB  - An experimental study is presented on harmonic generation from solid surfaces
      using 27 ps Nd:glass laser pulses (lambda=1053 nm) in the intensity range of
      10(13)-10(15) W cm(-2). Second, third, and fourth harmonics emitted in the
      specular reflection direction showed intensity scaling exponents of 1.5, 1.8, and
      3.8 for an obliquely incident p-polarized laser beam, providing a conversion
      efficiency of 2x10(-8), 10(-10), and 5x10(-12) at 10(15) W cm(-2), respectively.
      Second and third harmonic radiation generated using an s-polarized pump was about
      10 and 100 times smaller, respectively, compared to that for the p-polarized
      laser radiation. Faraday rotation observed in the reflected fundamental radiation
      can explain the relative harmonic yields for the p and s polarizations of the
      pump beam.

PMID- 11308581
TI  - Stopping power of strongly coupled electronic plasmas: sum rules and asymptotic
      forms.
AB  - The stopping power of coupled electronic plasmas is investigated. Within the
      dielectric formalism and employing the method of frequency moments for the
      dielectric function we obtain a general formula describing the linear stopping
      power of a coupled plasma. Analytical results for the low- and high-projectile
      velocity asymptotic forms are obtained. A sum rule for the plasma heavy ions
      linear stopping power projectile velocity distribution is established to be
      related to the dielectric permeability "negative" frequency moment. This permits
      for a simple interpretation of stopping power data.

PMID- 11308582
TI  - Dispersion of meteor trails in the geomagnetic field.
AB  - A meteor trail is modeled by a long column of weakly ionized plasma, whose
      dispersion is controlled by the geomagnetic field and the requirement to maintain
      effective space charge neutrality. First we consider scattering of a radar signal
      from an underdense trail and derive an expression for the amplitude of the
      backscattered signal as a function of time. Then, starting from the basic
      momentum balance equations for electrons and ions in a partially ionized plasma,
      we require divergences of ion and electron fluxes to be equal, plus assume
      equality of the flux components along the magnetic field direction. The analysis
      is really applicable to a whole range of plasma problems, although we focus upon
      meteor trails for now. It is found that charged particle densities satisfy a
      diffusion equation and we obtain an expression for the ambipolar diffusion tensor
      and expressions for the ambipolar electric field, valid for arbitrary relative
      orientations of the magnetic field and meteor trail axis. Results are somewhat
      different from previous analyses in the meteor literature.

PMID- 11308583
TI  - Kinetic modeling of relaxation phenomena after photodetachment in a rf
      electronegative SiH4 discharge.
AB  - The global relaxation process after pulsed laser induced photodetachment in a rf
      electronegative SiH4 discharge is studied by a self-consistent kinetic one
      dimensional particle-in-cell-Monte Carlo model. Our results reveal a
      comprehensive physical picture of the relaxation process, including the main
      plasma variables, after a perturbation up to the full recovery of the steady
      state. A strong influence of the photodetachment on the discharge is found, which
      results from an increase of the electron density, leading to a weaker bulk field,
      and hence to a drop in the high energy tail of the electron energy distribution
      function (EEDF), a reduction of the reaction rates of electron impact attachment
      and ionization, and a subsequent decrease of the positive and negative ion
      densities. All the plasma quantities related to electrons recover synchronously.
      The recovery time of the ion densities is about 1-2 orders of magnitude longer
      than that of the electrons due to different recovery mechanisms. The modeled
      behavior of all the charged particles agrees very well with experimental results
      from the literature. In addition, our work clarifies some unclear processes
      assumed in the literature, such as the relaxation of the EEDF, the evolution of
      the electric field, and the recovery of negative ions.

PMID- 11308584
TI  - Generation of fast electrons by breaking of a laser-induced plasma wave.
AB  - A one-dimensional model for fast electron generation by an intense, nonevolving
      laser pulse propagating through an underdense plasma has been developed. Plasma
      wave breaking is considered to be the dominant mechanism behind this process, and
      wave breaking both in front of and behind the laser pulse is discussed. Fast
      electrons emerge as a short bunch, and the electrostatic field of this bunch is
      shown to limit self-consistently the amount of generated fast electrons.

PMID- 11308585
TI  - Time-resolved x-ray K-shell spectra from high density plasmas generated by
      ultrashort laser pulses.
AB  - We present time-resolved x-ray spectra of C, F, Na, and Al, generated by focusing
      ultrashort frequency doubled Ti:sapphire laser pulses on solid plane targets.
      Using a high resolution x-ray streak camera in combination with a laser triggered
      accumulation system, we achieved a time resolution of 1.7 ps when adding the x
      ray signal of many thousands of laser shots. K-shell resonance line emission with
      a duration in the range of 2-4 ps is observed. Ly alpha emission is generally
      observed to be faster than He alpha emission and the x-ray pulse duration is
      observed to decrease with increasing atomic number. A hydrodynamic code in
      combination with an atomic kinetics code is applied for simulation of time
      resolved plasma emission, showing good agreement with experimental data.

PMID- 11308586
TI  - Experimental verification of semiclassical and RPA calculations of the static
      conductivity in moderately nonideal plasmas.
AB  - We present an experimental verification of the semiclassical theory for static
      conductivity calculations in the case of moderately nonideal plasmas. Such
      plasmas are produced in linear flashlamps filled with pure helium and are
      characterized by on axis electron densities in the range 2x10(17)-1.7x10(18) cm(
      3) and temperatures (2-3)x10(4) K. Precise measurements of the discharge
      electrical parameters have been carried out and in each case the impedance of the
      plasma was compared with the calculated value using the semiclassical theory,
      which is a simpler approximation than the quantum-mechanical theory based on the
      random-phase approximation.

PMID- 11308587
TI  - Spatiotemporal filamentary patterns in a dc-driven planar gas discharge system.
AB  - In a dc-driven planar gas discharge system with a semiconductor electrode, the
      homogeneous stationary discharge state can be destabilized in favor of current
      filaments. A filament consists of a succession of spatially confined
      breakthroughs of the gas layer that repeatedly take place at approximately the
      same position. A pulsating filament is thus slowly moving over the active area of
      the system. At fixed parameters, processes of creation and quenching of filaments
      are observed, while their average spatial density depends on control parameters.
      Depending on the density, filaments arrange in different configurations. At an
      intermediate value of filament density, a pattern on a two-dimensional domain is
      found: it is a spatially anisotropic chain pattern that is specified by two
      characteristic spatial scales. It is suggested that the observed phenomena are
      due to a Hopf-Turing instability arising in the system.

PMID- 11308588
TI  - Anomalous electron mobility in a coaxial Hall discharge plasma.
AB  - A comprehensive analysis of measurements supporting the presence of anomalous
      cross-field electron mobility in Hall plasma accelerators is presented.
      Nonintrusive laser-induced fluorescence measurements of neutral xenon and ionized
      xenon velocities, and various electrostatic probe diagnostic measurements are
      used to locally determine the effective electron Hall parameter inside the
      accelerator channel. These values are then compared to the classical (collision
      driven) Hall parameters expected for a quiescent magnetized plasma. The results
      indicate that in the vicinity of the anode, where there are fewer plasma
      instabilities, the electron-transport mechanism is likely elastic collisions with
      the background neutral xenon. However, we find that in the vicinity of the
      discharge channel exit, where the magnetic field is the strongest and where there
      are intense fluctuations in the plasma properties, the inferred Hall parameter
      departs from the classical value, and is close to the Bohm value of
      (omega(ce)tau)(eff) approximately 16. These results are used to support a simple
      model for the Hall parameter that is based on the scalar addition of the electron
      collision frequencies (elastic collision induced plus fluctuation induced), as
      proposed by Boeuf and Garrigues [J. Appl. Phys. 84, 3541 (1998)]. The results
      also draw attention to the possible role of fluctuations in enhancing electron
      transport in regions where the electrons are highly magnetized.

PMID- 11308589
TI  - Compressing and focusing a short laser pulse by a thin plasma lens.
AB  - We consider the possibility of using a thin plasma slab as an optical element to
      both focus and compress an intense laser pulse. By thin we mean that the focal
      length is larger than the lens thickness. We derive analytic formulas for the
      spot size and pulse length evolution of a short laser pulse propagating through a
      thin uniform plasma lens. The formulas are compared to simulation results from
      two types of particle-in-cell code. The simulations give a greater final spot
      size and a shorter focal length than the analytic formulas. The difference arises
      from spherical aberrations in the lens which lead to the generation of higher
      order vacuum Gaussian modes. The simulations also show that Raman side scattering
      can develop. A thin lens experiment could provide unequivocal evidence of
      relativistic self-focusing.

PMID- 11308590
TI  - Dust acoustic solitons with variable particle charge: role of the ion
      distribution.
AB  - Dust-acoustic solitons of large amplitude with variable particle charge are
      studied using the Sagdeev quasipotential analysis. Two limiting cases of ion
      distribution are considered separately: Boltzmann and highly energetic cold ions.
      It is shown that in both cases only compressive (density) solitons are possible.
      The charge variation is not important in rarefied particle clouds, but becomes
      crucial if the particle number density is sufficiently high. Analytical
      expressions for the range of Mach numbers where solitons might exist are
      obtained. It is found that solitons are allowed in the supersonic regime, and
      that in dense clouds the width of the Mach number range remains finite for the
      Boltzmann ions, but tends to zero for highly energetic ions.

PMID- 11308591
TI  - Use of gamma-ray-generating nuclear reactions for temperature diagnostics of DT
      fusion plasma.
AB  - A diagnostic application of gamma rays emitted in 6Li+D and 6Li+T nuclear
      reactions induced by admixing a small amount of 6Li in DT fusion plasma is
      investigated. It is shown that the reaction-produced monochromatic gamma quanta
      with energies E(gamma)=0.429, 0.478, and 0.981 MeV can be used for ion
      temperature measurements in DT plasma. The proposed measurements are expected to
      be essentially independent of the plasma density and its local fluctuations. The
      required reaction cross sections and the Maxwellian rate parameters of the 6Li+T
      gamma-ray production are calculated within a realistic nuclear model.

PMID- 11308592
TI  - Gyrokinetic formula and experimental examination of the electron-beam
      misalignment effect on the efficiency of a cylindrical-cavity gyrotron
      oscillator.
AB  - By making use of the gyrokinetics of free-electron masers, the efficiency formula
      of a cylindrical-cavity gyrotron oscillator is presented, where the misalignment
      of the electron-beam axis to the cavity axis has been taken into account.
      Comparison with a recent experimental report [Int. J. Infrared and Millimeter
      Waves 19, 1303 (1998)] is made, which confirms the creditability of the
      gyrokinetic theory.

PMID- 11308593
TI  - Resonant production of secondary electrons generating a discrete energy structure
      in a magnetized electron beam system.
AB  - In a system of magnetized electron beams, multiplication of electrons can occur
      if the incident and return beams (the latter one is produced by secondary
      electrons emitted at the end of the incident beam) satisfy a resonance condition
      on the gyration phase. The beams propagate between two boundaries; one is an
      electron gun and the other is a Faraday cup detector. The resonance condition
      demands discrete energies (eigenvalues) of the Hamiltonian that generates a
      propagator of the beam. This model has been compared with Varma's formulation of
      discrete energies [R. K. Varma and A. M. Punithavelu, Mod. Phys. Lett. A 8, 167
      (1993)].

PMID- 11308594
TI  - Analytical calculation of the longitudinal space charge and resistive wall
      impedances in a smooth cylindrical pipe.
AB  - The longitudinal space charge and resistive wall impedances have been
      investigated in a smooth cylindrical beam pipe. At any point from the beam axis,
      we obtained an expression for the total impedance, which at the beam surface r=a
      for infinite pipe wall conductivity gives the expression for the total impedance
      that was derived by Zotter and Kheifets in studying the impedance of uniform
      beams in concentric cylindrical wall chambers, when a single cylindrical chamber
      is considered [B. W. Zotter and S. A. Kheifets, Impedances and Wakes in High
      Energy Particle Accelerators (World Scientific, Singapore, 1998), Chap. 6]. A
      fitting formula for the space-charge impedance at the beam surface (r=a), which
      is valid for arbitrary wavelengths, is given. Rather than calculating the
      impedance with the field on the axis [Joseph J. Bisognano, Fifth European
      Particle Accelerator Conference (EPAC96), edited by S. Myers, A. Pacheco, R.
      Pascual, Ch. Petit-Jean-Genaz, and J. Poole (Institute of Physics, Bristol,
      1996), Vol. 1, p. 328], the fitting formula is obtained by averaging over the
      transverse beam distribution. We also give another approach for the calculation
      of the resistive wall impedance using the flux of the Poynting vector at the pipe
      wall and then compare it with the expression obtained from the volume integral
      over the beam distribution.

PMID- 11308595
TI  - Diffraction of short pulses with boundary diffraction wave theory.
AB  - The diffraction of short pulses is studied on the basis of the Miyamoto-Wolf
      theory of the boundary diffraction wave, which is a mathematical formulation of
      Young's idea about the nature of diffraction. It is pointed out that the
      diffracted field is given by the superposition of the boundary wave pulse (formed
      by interference of the elementary boundary diffraction waves) and the geometric
      (direct) pulse (governed by the laws of geometrical optics). The case of a
      circular aperture is treated in details. The diffracted field on the optical axis
      is calculated analytically (without any approximation) for an arbitrary temporal
      pulse shape. Because of the short pulse duration and the path difference the
      geometric and the boundary wave pulses appear separately, i.e., the boundary
      waves are manifested in themselves in the illuminated region (in the sense of
      geometrical optics). The properties of the boundary wave pulse is discussed. Its
      radial intensity distribution can be approximated by the Bessel function of zero
      order if the observation points are in the illuminated region and far from the
      plane of the aperture and close to the optical axis. Although the boundary wave
      pulse propagates on the optical axis at a speed exceeding c, it does not
      contradict the theory of relativity.

PMID- 11308596
TI  - Analysis of polarization effects on nanoscopic objects in the near-field optics.
AB  - This paper deals with the analysis of polarization around nanoscopic objects in
      near-field optics. The objects are illuminated through a transparent glass
      substrate under the condition of total internal reflection. The use of dielectric
      and metallic materials in the optical images is discussed. Using numerical
      simulations based on the Green's dyadic technique, we compute the total
      transmitted intensity of the scattered light and the different Cartesian
      components associated with the electric field in the attenuated total reflection
      configuration at constant height. The role of localized plasmon resonance is
      brought to the fore in the optical images of nanoscopic metallic objects. This
      paper shows that it is possible to reduce the interferences due to backward
      scattering from nanoscopic objects thanks to this polarimetry analysis.

PMID- 11308597
TI  - Propagation of photons in resting and moving media.
AB  - The propagation of photon in a dielectric may be described with the help of the
      scalar and vector potentials of the medium. The main novelty of the paper is that
      the concept of the vector potential (which is connected with the velocity of the
      medium) can be extended to relativistic velocities of the medium. The position
      dependent photon wave function was used to describe the propagation of the
      photon. The new concepts of the velocity of photon as particle and the photon
      mass in the dielectric medium were proposed.

PMID- 11308598
TI  - Conditions for anomalous acousto-optical diffraction by backward propagating
      acoustic waves.
AB  - Experimental evidence is given of acoustic plate waves, whose group velocity is
      contradirected with respect to the phase velocity, through a determination of the
      acoustic wavelength dependence on frequency, in a limited range of frequencies.
      The dependence dLambda/dOmega>0 between wavelength and frequency is
      experimentally verified, as the required condition for acousto-optical
      diffraction, where higher frequency components would scatter light into smaller
      diffraction angles.

PMID- 11308599
TI  - Localization-induced coherent backscattering effect in wave dynamics.
AB  - We investigate the statistics of single-mode delay times of waves reflected from
      a disordered waveguide in the presence of wave localization. The distribution of
      delay times is qualitatively different from the distribution in the diffusive
      regime, and sensitive to coherent backscattering: The probability of finding
      small delay times is enhanced by a factor close to sqrt[2] for reflection angles
      near the angle of incidence. This dynamic effect of coherent backscattering
      disappears in the diffusive regime.

PMID- 11308600
TI  - Soliton scattering from a finite cnoidal wave train in a fiber.
AB  - We analyze the scattering of a soliton from a cnoidal wave train in a fiber
      theoretically as well as numerically. Solitons recover their original shapes and
      velocities after collisions, while shapes of cnoidal waves are nearly preserved
      during collisions. The effect of collisions is described by the change of
      velocities of solitons, and the theoretical predictions are in good agreement
      with numerical results.

PMID- 11308601
TI  - Chemical reaction-diffusion implementation of finding the shortest paths in a
      labyrinth.
AB  - An experimental technique for finding the shortest paths in a labyrinth is
      elaborated on based on chemical reaction-diffusion media. The system designed has
      hybrid architecture that combines an information-processing reaction-diffusion
      medium performing operations of high computational complexity with a digital
      computer carrying out supplementary operations. Two principal points are assumed
      as a basis for this design. They are the following: a light-sensitive Belousov
      Zhabotinsky-type reagent chosen as a reaction-diffusion medium that offers the
      opportunity to simulate a labyrinth and spread wave evolution by its images
      stored in the medium; fast light-induced phase wave processes that spread through
      the labyrinth in seconds instead of the dozens of minutes typical of trigger
      waves inherent in reaction-diffusion media. Images of consecutive wave-spreading
      steps are stored in the memory of a digital computer. These images are used to
      determine the shortest paths based on the additional procedure of testing for the
      connectedness of labyrinth fragments.

PMID- 11308602
TI  - Propagation of solitons in a randomly perturbed Ablowitz-Ladik chain.
AB  - This paper deals with the transmission of a soliton in a discrete, nonlinear, and
      random medium. A random lattice nonlinear Schrodinger equation is considered,
      where the randomness holds in the on-site potential or in the coupling
      coefficients. We study the interplay of nonlinearity, randomness, and
      discreteness. We derive effective evolution equations for the soliton parameters
      by applying a perturbation theory of the inverse scattering transform and limit
      theorems of stochastic calculus.

PMID- 11308603
TI  - Classical decay of Coulomb charges.
AB  - In this paper we postulate and solve the following problem: Prove in the
      framework of Newtonian mechanics that three Coulomb charges (-1,Q,Q) for Q>4 will
      leave any initial volume in a finite time and estimate this time. We also discuss
      possible generalizations of the problem and its relation to stability of ions and
      molecules.

PMID- 11308604
TI  - Stimulated transitions between the self-trapped states of the nonlinear
      Schrodinger equation.
AB  - We investigate a particle confined within a double-well potential, its behavior
      described by a one-dimensional nonlinear Schrodinger equation. Transitions
      between the two lowest self-trapped states of this system are studied, in the two
      mode approximation, under the influence of the external time-dependent
      perturbation. If the perturbation is harmonic in time, with the frequency omega,
      then transitions between the states become possible if the amplitude of the
      perturbation F exceeds some threshold value F(c)(omega); above this threshold
      motion of the system becomes chaotic. If the perturbation is broadband noise,
      then transitions between the states are possible at arbitrarily small F and occur
      in the process of the system's energy diffusion.

PMID- 11308605
TI  - Bright stationary solitary waves in deep gratings with a quadratic nonlinearity.
AB  - We present localized, bright, stationary soliton solutions to the coupled-mode
      equations for quadratically nonlinear media with a deep grating. We find that the
      required peak intensities can be significantly lower than might be expected from
      a shallow grating treatment.

PMID- 11308606
TI  - Internal eigenstate problem: the trial state method.
AB  - It is shown that the device of adding a special trial state to a basis set, thus
      augmenting by 1 the dimension of any complex matrix being studied, leads to a
      formalism that permits the application of the wave operator approach to
      calculating the internal spectrum of the matrix as well as the action of the
      resolvent operator (E-H)(-1) on an arbitrary vector in the original N-dimensional
      space. Two calculational variants of the method are described and both are tested
      by studying the problem of a short laser pulse interacting with a H+2 ion.

PMID- 11308607
TI  - Simplest random K-satisfiability problem.
AB  - We study a simple and exactly solvable model for the generation of random
      satisfiability problems. These consist of gammaN random boolean constraints which
      are to be satisfied simultaneously by N logical variables. In statistical
      mechanics language, the considered model can be seen as a diluted p-spin model at
      zero temperature. While such problems become extraordinarily hard to solve by
      local search methods in a large region of the parameter space, still at least one
      solution may be superimposed by construction. The statistical properties of the
      model can be studied exactly by the replica method and each single instance can
      be analyzed in polynomial time by a simple global solution method. The
      geometrical and topological structures responsible for dynamic and static phase
      transitions as well as for the onset of computational complexity in the local
      search method are thoroughly analyzed. Numerical analysis on very large samples
      allows for a precise characterization of the critical scaling behavior.

PMID- 11308608
TI  - Clustering of points randomly distributed in n-dimensional space.
AB  - We consider clusters formed by points randomly distributed in space, each point
      being connected to its nearest neighbor or to its nearest and next nearest
      neighbors. The size distribution of such clusters in n-dimensional space is
      presented.

PMID- 11308609
TI  - Exact expressions for minor hysteresis loops in the random field Ising model on a
      Bethe lattice at zero temperature.
AB  - We obtain exact expressions for the minor hysteresis loops in the ferromagnetic
      random field Ising model on a Bethe lattice at zero temperature in the case when
      the driving field is cycled infinitely slowly.

PMID- 11308610
TI  - Control of projective synchronization in chaotic systems.
AB  - We show that the scaling factor of projective synchronization in coupled
      partially linear systems is unpredictable. This gives rise to the difficulty in
      estimating the state of synchronized dynamics. We therefore propose a control
      method to manipulate the scaling factor onto any desired value so that the
      synchronization can be managed in a preferred way. A control law is derived based
      on the mechanism of projective synchronization of three-dimensional systems and
      an application is illustrated for the Lorenz system.

PMID- 11308611
TI  - Atomic diamagnetism within a dense plasma.
AB  - In this paper we have studied the influence of plasma electron polarization
      around a charged atomic impurity on the diamagnetic response behavior of the
      impurity ion, when subject to large-scale magnetic fields within high-density
      plasmas. As a typical example, we consider the two-electron ion C4+ (Z=6) in its
      ground state 1s(2):(1)S. Calculation performed within the Hartree-Fock
      approximation under the framework of the ion sphere model for the plasma-embedded
      impurity ion suggests that, in a high-density regime, the diamagnetic shift of
      the ground state is a bivariate function of the magnetic field and the plasma
      electron density. Also, it is shown that the magnitude of the diamagnetic
      susceptibility of the impurity ion increases with increasing plasma electron
      density, implying that the ion becomes more diamagnetic as a direct consequence
      of the increased orbital radii of its bound charges under enhanced density
      induced screening.

PMID- 11308612
TI  - "Superluminal" transmission of light pulses through optically opaque barriers.
AB  - Using simple considerations of causal electrodynamics we analyze the occurrence
      of superluminal transmission of light pulses through optically opaque barriers.
      We find that the phenomenon appears whenever the main frequency components of the
      pulse are confined to frequency regions where the presence of the barrier
      decreases the density of states of the electromagnetic modes of the system. We
      also show that these frequency regions correspond to the transmission gaps of
      sufficiently wide barriers. We discuss a simple theory for the density of states
      of the barrier system and compare the results of such a theory with exact
      numerical calculations.

PMID- 11308613
TI  - Self-consistent photonic band structure of dielectric superlattices containing
      nonlinear optical materials.
AB  - The theory of photonic crystals is extended to include the optical Kerr effect
      taking place in weak third-order, nonlinear materials present in the unit cell.
      The influence on the dispersion relations of the illumination caused by a single
      Bloch mode transiting through the crystal structure is examined. Special
      attention is given to the modification of the photonic gap width and position.
      Assuming an instantaneous change of refractive index with illumination, the
      nonlinear band structure problem is solved as a sequence of ordinary, linear band
      structure calculations, carried out in a plane-wave field representation.

PMID- 11308614
TI  - Comment on "pi kinks in strongly ac driven sine-Gordon systems".
AB  - V. Zharnitsky, I. Mitkov, and N. Gronbech-Jensen [Phys. Rev. E 58, 1, R52 (1998)]
      found that pi kinks can propagate in strongly perturbed, directly driven rescaled
      sine-Gordon system provided that the parameters are chosen to make 2pi kink
      localization vanish. In this paper we would like to note that beside pi and 2pi
      kinks there can exist other kinklike solutions due to the fact that two unstable
      equilibria in the sine-Gordon phase emerging at a critical value of the drive
      amplitude are not necessarily separated by pi, to the contrary with the result of
      Zharnitsky, Mitkov, and Gronbech-Jensen. As a result, for the nondissipative
      system two one-parameter families of kink solutions exist that in the degenerate
      case become a one-parameter family of pi-kink solutions obtained in Zharnitsky,
      Mitkov, and Gronbech-Jensen. In the dissipative case velocity is selected for
      each of the two families of kink solutions by the balance between perturbations.

PMID- 11308615
TI  - Comment on "Efficient stress relaxation in molecular dynamics simulations of
      semiflexible n-alkanes".
AB  - Contrary to the findings of Mulders, Toxvaerd, and Kneller [Phys. Rev. E 58, 6766
      (1998)] (MTK), we are unable to discern any difference in the behavior of long
      chain alkanes simulated by molecular dynamics at constant pressure using either
      atomic or molecular scaling schemes. This result confirms our previous study [M.
      Marchi and P. Procacci, J. Chem. Phys. 109, 5194 (1998)] on hydrated proteins
      published at the same time as the MTK's paper. This Comment indicates that errors
      in the calculation of the pressure tensor might be responsible for at least a
      part of the MTKs results.

PMID- 11308617
TI  - Nonlinear equation for anomalous diffusion: Unified power-law and stretched
      exponential exact solution.
AB  - The nonlinear diffusion equation partial delta rho/delta t=D Delta rho(nu) is
      analyzed here, where Delta[triple bond](1/r(d-1))(delta/delta r)r(d-1-theta)
      delta/delta r, and d, theta, and nu are real parameters. This equation unifies
      the anomalous diffusion equation on fractals (nu=1) and the spherical anomalous
      diffusion for porous media (theta=0). An exact point-source solution is obtained,
      enabling us to describe a large class of subdiffusion [ theta>(1-nu)d], "normal"
      diffusion [theta=(1-nu)d] and superdiffusion [theta<(1-nu)d]. Furthermore, a
      thermostatistical basis for this solution is given from the maximum entropic
      principle applied to the Tsallis entropy.

PMID- 11308618
TI  - Molecular motor based entirely on the Coulomb interaction.
AB  - A molecular motor is introduced which is composed of charges only and which does
      not contain any potential or interaction besides the Coulomb one. The motor is
      shown to transform efficiently a driven random rotation into a directed
      translational motion. The direction of translational motion can be chosen
      dynamically, so that a "forward gear," a "reverse gear," and even a "neutral
      gear" exist. The high efficiency stems from the fact that this motor only steps
      in the direction determined by the chosen gear.

PMID- 11308619
TI  - Dissipative Abelian sandpiles and random walks.
AB  - We show that the dissipative Abelian sandpile on a graph L can be related to a
      random walk on a graph that consists of L extended with a trapping site. From
      this relation it can be shown, using exact results and a scaling assumption, that
      the correlation length exponent nu of the dissipative sandpiles always equals
      1/d(w), where d(w) is the fractal dimension of the random walker. This leads to a
      new understanding of the known result that nu=1/2 on any Euclidean lattice. Our
      result is, however, more general, and as an example we also present exact data
      for finite Sierpinski gaskets, which fully confirm our predictions.

PMID- 11308620
TI  - Undulations in a confined lamellar system with surface anchoring.
AB  - We visualize undulations in layered systems using a cholesteric stripe phase with
      a macroscopic supramicron periodicity. The wave vector of stripe pattern is in
      the cell's plane. The undulation is induced by an in-plane magnetic field normal
      to the stripes. The observed displacement of layers is much larger than the value
      predicted by the Helfrich-Hurault classic theory. We propose a model of
      undulations that explains the data by finite surface anchoring of layers.

PMID- 11308621
TI  - Averaging rheological quantities in descriptions of soft glassy materials.
AB  - Many mean-field models have been introduced to describe the mechanical behavior
      of glassy materials. They often rely on averages performed over distributions of
      elements or states. We here underline that averaging is a more intricate
      procedure in mechanics than in more classical situations such as phase
      transitions in magnetic systems. This leads us to modify the predictions of the
      recently proposed soft glassy rheology model for soft glassy materials, for which
      we suggest that the viscosity should diverge at the glass transition temperature
      T(g) with an exponential form eta - exp[A/(T-T(g))].

PMID- 11308622
TI  - Social games in a social network.
AB  - We study an evolutionary version of the Prisoner's Dilemma game, played by agents
      placed in a small-world network. Agents are able to change their strategy,
      imitating that of the most successful neighbor. We observe that different
      topologies, ranging from regular lattices to random graphs, produce a variety of
      emergent behaviors. This is a contribution towards the study of social phenomena
      and transitions governed by the topology of the community.

PMID- 11308623
TI  - Anomalous swelling in phospholipid bilayers is not coupled to the formation of a
      ripple phase.
AB  - Aligned stacks of monomethyl and dimethyl dimyristoyl phosphatidylethanolamine
      (DMPE) lipid bilayers, like the much studied dimyristoyl PC (DMPC) bilayers,
      swell anomalously in a critical fashion as the temperature is decreased within
      the fluid phase towards the main transition temperature, T(M). Unlike DMPC
      bilayers, both monomethyl and dimethyl DMPE undergo transitions into a gel phase
      rather than a rippled phase below T(M). Although it is not fully understood why
      there is anomalous swelling, our present results should facilitate theory by
      showing that the formation of the phase below T(M) is not related to critical
      phenomena above T(M).

PMID- 11308624
TI  - Icosahedron-fcc transition size by molecular dynamics simulation of Lennard-Jones
      clusters at a finite temperature.
AB  - We studied finite-temperature ensembles of solid clusters produced by cooling
      liquid droplets either by evaporation or by a thermostat through a molecular
      dynamics calculation using the Lennard-Jones potential. The ensembles consist of
      either single or binary component clusters with 25% of the atoms 8% smaller in
      diameter than the other 75%. These clusters (380 clusters in total) exhibit
      various structures in the size range of n=160-2200, where n is the number of
      atoms in a cluster. For increasing size, the clusters show a gradual transition
      from icosahedral to a variety of structures: decahedral, face centered cubic, a
      small amount of hexagonal, and some icosahedral structures. They are asymmetrical
      or faulted. Electron diffraction patterns calculated with average structure
      factors of clusters after grouping them into several size regions are very
      similar to those experimentally observed. The size transition is around n=450 for
      single component clusters whatever the cooling process, evaporation or
      thermostat. This size is smaller than the experimental transition size estimated
      for argon clusters formed in a supersonic expansion. The transition size for
      binary component clusters is around n=600 for evaporative cooling, and larger for
      thermostatic cooling. The larger transition size found for the binary component
      clusters is consistent with the large icosahedral Au-Fe and Au-Cu alloy clusters
      observed experimentally.

PMID- 11308625
TI  - Weighted density functional theory for simple fluids: supercritical adsorption of
      a Lennard-Jones fluid in an ideal slit pore.
AB  - The adsorption of a Lennard-Jones fluid in an ideal slit pore is studied using
      weighted density functional theory. The intrinsic Helmholtz free-energy
      functional is separated into repulsive and attractive contributions. Rosenfeld's
      accurate fundamental measure functional is employed for the repulsive functional
      while another weighted density functional method is employed for the attractive
      functional. This other method requires an accurate equation of state for the bulk
      fluid and an accurate pair-direct correlation function for a uniform fluid,
      determined analytically or numerically. The results for this theory are compared
      against mean-field density functional theory and grand canonical ensemble
      simulation results, modeling the adsorption of ethane in a graphite slit. The
      results indicate that the weighted density functional method applied to the
      attractive functional can offer a significant increase in accuracy over the mean
      field theory.

PMID- 11308627
TI  - Numerical study of persistence in models with absorbing states.
AB  - Extensive Monte Carlo simulations are performed in order to evaluate both the
      local (straight theta(l)) and global (straight theta(g)) persistence exponents in
      the Ziff-Gulari-Barshad (ZGB) [Phys. Rev. Lett. 56, 2553 (1986)] irreversible
      reaction model. At the second-order irreversible phase transition (IPT) we find
      that both the local and the global persistence exhibit power-law behavior with a
      crossover between two different time regimes. On the other hand, at the ZGB first
      order IPT, active sites are short lived and the persistence decays more abruptly;
      it is not clear whether it shows power-law behavior or not. In order to analyze
      universality issues, we have also studied another model with absorbing states,
      the contact process, and evaluated the local persistence exponent in dimensions
      from 1 to 4. A striking apparent superuniversality is reported: the local
      persistence exponent seems to coincide in both one- and two-dimensional systems.
      Some other aspects of persistence in systems with absorbing states are also
      analyzed.

PMID- 11308626
TI  - Random Ginzburg-Landau model revisited: reentrant phase transitions.
AB  - We analyze the phase diagram of the random Ginzburg-Landau model, where a
      quenched dichotomous noise affects the control parameter. We show that the system
      exhibits two types of counterintuitive reentrant second-order phase transitions.
      In the first case, increasing the coupling drives the system from a disordered to
      an ordered state and then back to a disordered state. In the second case,
      increasing the intensity of the quenched noise, the system goes from an ordered
      phase to a disordered phase and back to an ordered state. We discuss the general
      mechanism that produces these reentrant phase transitions, showing that it may
      appear in other physical systems, such as a modification of the spin-1 Blume
      Capel model proposed to describe the critical behavior of helium mixtures in a
      random medium.

PMID- 11308628
TI  - Ground-state fluctuations in finite Fermi systems.
AB  - We consider a small and fixed number of fermions in a trap. The ground state of
      the system is defined at T=0. For a given excitation energy, there are several
      ways of exciting the particles from this ground state. We formulate a method for
      calculating the number fluctuation in the ground state using microcanonical
      counting, and implement it for noninteracting fermions in harmonic confinement.
      This exact calculation for fluctuation, when compared with canonical or grand
      canonical ensemble averaging, gives considerably different results. This
      difference is expected to persist at low excitation even when the fermion number
      in the trap is large. For comparison, the well-known bosonic results are also
      given.

PMID- 11308629
TI  - Slow dynamics and aging in a constrained diffusion model.
AB  - We carry out a complete analysis of the schematic diffusive model recently
      introduced for the description of supercooled liquids and glassy systems above
      the glass temperature. The model is described by a trivial equilibrium measure
      and the presence of kinetics constraints is mimicked through a rapidly decreasing
      mobility at high particle density. The governing equation describing a sudden
      quench process is investigated analytically in a mean field approach and by means
      of numerical simulations. For deep quenches a long lasting off-equilibrium
      dynamics is observed in dense systems before equilibration is achieved, where
      time translational invariance lacks and the system ages. The kinetics is slow in
      this time domain since the average particle diffusivity D decreases in time, as
      opposed to the standard diffusion case of a constant D, that is recovered only in
      equilibrium. The autocorrelation function decays slower than an exponential,
      falling in mean field as an enhanced power law. The linear response function is
      computed and the modalities of the break-down of the fluctuation dissipation
      theorem are analytically investigated, showing that an effective temperature can
      be defined which slowly approaches the bath temperature from above.

PMID- 11308630
TI  - Effects of colored noise on stochastic resonance in a bistable system subject to
      multiplicative and additive noise.
AB  - The effects of colored noise on stochastic resonance (SR) in a bistable system
      driven by multiplicative colored noise and additive white noise and a periodic
      signal are studied by using the unified colored noise approximation and the
      theory of signal-to-noise ratio (SNR) in the adiabatic limit. In the case of no
      correlations between noises, there is an optimal noise intensities ratio R at
      which SNR is a maximum that identifies the characteristics of the SR when the
      correlation time tau of the multiplicative colored noise is small. However, when
      tau is increased, a second optimal value of R appears, and two peaks appear in
      the SNR simultaneously. In the case of correlations between noises, the SNR is
      not only dependent on the correlation time tau, but also on the intensity of
      correlations between noises. Moreover, the double peak phenomenon can also appear
      as tau is increased in certain situations.

PMID- 11308631
TI  - Kac-potential treatment of nonintegrable interactions.
AB  - We consider d-dimensional systems with nonintegrable, algebraically decaying
      pairwise interactions. It is shown that, upon the introduction of periodic
      boundary conditions and a long-distance cutoff in the interaction range, the bulk
      thermodynamics can be obtained rigorously by means of a Kac-potential treatment,
      leading to an exact, mean-field-like theory. This explains various numerical
      results recently obtained for finite systems in the context of "nonextensive
      thermodynamics," and in passing exposes a strong regulator dependence not
      discussed in these studies. Our findings imply that, contrary to some claims,
      Boltzmann-Gibbs statistics are sufficient for a standard description of this
      class of nonintegrable interactions.

PMID- 11308632
TI  - Simple model of a random walk with arbitrarily long memory.
AB  - We present a generalization of the persistent random-walk model in which the step
      at time n depends on the state of the step at time n-T, for arbitrary T. This
      gives rise to arbitrarily long memory effects, yet by an appropriate
      transformation the model is tractable by essentially the same techniques
      applicable to the usual persistent random-walk problem. We apply our results to
      the specific case of delayed "step" persistence, and analyze its asymptotic
      statistical properties.

PMID- 11308633
TI  - Mirror symmetry breaking through an internal degree of freedom leading to
      directional motion.
AB  - We analyze here the minimal conditions for directional motion (net flow in phase
      space) of a molecular motor placed on a mirror-symmetric environment and driven
      by a center-symmetric and time-periodic force field. The complete
      characterization of the deterministic limit of the dissipative dynamics of
      several realizations of this minimal model reveals a complex structure in the
      phase diagram in parameter space, with intertwined regions of pinning (closed
      orbits) and directional motion. This demonstrates that the mirror symmetry
      breaking, which is needed for directional motion to occur, can operate through an
      internal degree of freedom coupled to the translational one.

PMID- 11308634
TI  - Josephson vortex in a ratchet potential: theory.
AB  - We propose a type of Josephson vortex ratchet. In this system a Josephson vortex
      moves in a periodic asymmetric potential under the action of a deterministic or
      random force with zero time average. For some implementations the amplitude of
      the potential can be controlled during the experiment, thus allowing us to tune
      the performance of the system and build rocking as well as flashing ratchets. We
      discuss the differences between conventional and Josephson vortex ratchets and
      present a model describing the dynamics of the fluxon in such a system. We show
      numerical simulation results that predict rectification of a monochromatic,
      deterministic signal with zero time average. The investigation of this system may
      lead to the development of the fluxon rectifier-a device that produces a dc
      voltage from nonequilibrium fluctuations.

PMID- 11308635
TI  - Euler-Poincare characteristics of classes of disordered media.
AB  - We consider a family of statistical measures based on the Euler-Poincare
      characteristic of n-dimensional space that are sensitive to the morphology of
      disordered structures. These measures embody information from every order of the
      correlation function but can be calculated simply by summing over local
      contributions. We compute the evolution of the measures with density for a range
      of disordered microstructural models; particle-based models, amorphous
      microstructures, and cellular and foamlike structures. Analytic results for the
      particle-based models are given and the computational algorithm verified.
      Computational results for the different microstructures exhibit a range of
      qualitative behavior. A length scale is derived based on two-point
      autocorrelation functions to allow qualitative comparison between the different
      structures. We compute the morphological parameters for the experimental
      microstructure of a sandstone sample and compare them to three common stochastic
      model systems for porous media. None of the statistical models are able to
      accurately reproduce the morphology of the sandstone.

PMID- 11308636
TI  - Wetting of a symmetrical binary fluid mixture on a wall.
AB  - We study the wetting behavior of a symmetrical binary fluid below the demixing
      temperature at a nonselective attractive wall. Although it demixes in the bulk, a
      sufficiently thin liquid film remains mixed. On approaching liquid vapor
      coexistence, however, the thickness of the liquid film increases and it may demix
      and then wet the substrate. We show that the wetting properties are determined by
      an interplay of the two length scales related to the density and the composition
      fluctuations. The problem is analyzed within the framework of a generic two
      component Ginzburg-Landau functional (appropriate for systems with short-ranged
      interactions). This functional is minimized both numerically and analytically
      within a piecewise parabolic potential approximation. A number of surface
      transitions are found, including first-order demixing and prewetting, continuous
      demixing, a tricritical point connecting the two regimes, or a critical end point
      beyond which the prewetting line separates a strongly and a weakly demixed film.
      Our results are supported by detailed Monte Carlo simulations of a symmetrical
      binary Lennard-Jones fluid at an attractive wall.

PMID- 11308637
TI  - Diffusion and localization of surface gravity waves over irregular bathymetry.
AB  - An interaction of a linear surface gravity wave with weakly irregular one
      dimensional bathymetry has been analyzed using the diagrammatic technique. The
      Boltzmann diffusion coefficient and the Anderson localization length for the wave
      energy density are expressed analytically via a correlation function of
      irregularities of the sea floor. The results are applied to different
      topographies. The effect of a finite region of irregularities, viscous damping,
      wave interaction, current, geometrically diffuse wave source, and anisotropy on
      localization is briefly discussed. The theory provides a scenario for the
      observation of large scale Anderson localization phenomenon in a tank or possibly
      in coastal waters.

PMID- 11308638
TI  - Generic van der Waals equation of state and statistical mechanical
      representations of the van der Waals parameters.
AB  - In this paper, we show that in the case of the potential made up of a repulsive
      and an attractive part the virial equation of state can be put into a form
      similar to the van der Waals equation of state and thus the form of the van der
      Waals equation of state is generic to such a class of potentials. The derivation
      provides exact statistical mechanical representations for the van der Waals
      parameters. The generic van der Waals parameters are evaluated as functions of
      density and temperature by using the Percus-Yevick integral equation for the pair
      correlation function in the case of a square-well potential. They become
      disjointed functions of density, which are not defined in a density interval in
      the subcritical regime, if the temperature is less than the critical temperature.
      On the basis of the numerical solution results for the parameters we conjecture
      that they are irrational functions of density and thus nonanalytic.

PMID- 11308639
TI  - Mean-atom-trajectory model for the velocity autocorrelation function of monatomic
      liquids.
AB  - We present a model for the motion of an average atom in a liquid or supercooled
      liquid state and apply it to calculations of the velocity autocorrelation
      function Z(t) and diffusion coefficient D. The model trajectory consists of
      oscillations at a distribution of frequencies characteristic of the normal modes
      of a single potential valley, interspersed with position- and velocity-conserving
      transits to similar adjacent valleys. The resulting predictions for Z(t) and D
      agree remarkably well with molecular dynamics simulations of Na at up to almost
      three times its melting temperature. Two independent processes in the model relax
      velocity autocorrelations: (a) dephasing due to the presence of many frequency
      components, which operates at all temperatures but which produces no diffusion,
      and (b) the transit process, which increases with increasing temperature and
      which produces diffusion. Because the model provides a single-atom trajectory in
      real space and time, including transits, it may be used to calculate all single
      atom correlation functions.

PMID- 11308640
TI  - Critical properties and phase separation in lattice Boltzmann fluid mixtures.
AB  - Basic equilibrium properties of lattice Boltzmann (LB) fluid mixtures
      (coexistence curve, surface tension, interfacial profile, correlation length) are
      calculated to characterize the critical phenomena occurring in these model
      liquids and to establish a reduced variable description allowing a comparison
      with real fluid mixtures. We observe mean-field critical exponents and amplitudes
      so that the LB model may be useful for modeling high molecular weight polymer
      blends and other fluid mixtures approximated over a wide temperature range by
      mean-field theory. We also briefly consider phase separation under quiescent and
      shearing conditions and point out the strong influence of interacting boundaries
      on the qualitative form of the late-stage phase-separation morphology.

PMID- 11308641
TI  - Criterion for determining clustering versus reentrant melting behavior for
      bounded interaction potentials.
AB  - We examine in full generality the phase behavior of systems whose constituent
      particles interact by means of potentials that do not diverge at the origin, are
      free of attractive parts, and decay fast enough to zero as the interparticle
      separation r goes to infinity. By employing a mean field-density functional
      theory which is shown to become exact at high temperatures and/or densities, we
      establish a criterion that determines whether a given system will freeze at all
      temperatures or it will display reentrant melting and an upper freezing
      temperature.

PMID- 11308642
TI  - Pressure dependence of structural relaxation time in terms of the Adam-Gibbs
      model.
AB  - A new equation describing the behavior of the structural relaxation time,
      tau(T,P), as a function of both pressure and temperature, is discussed. This
      equation has been derived from the Adam-Gibbs theory by writing the
      configurational entropy, S(c), in terms of the excess thermal heat capacity and
      of the molar thermal expansion. Consequently, the parameters introduced in the
      expression are directly related to specific physical properties of the material,
      such as the thermal expansion coefficient alpha and the isothermal bulk modulus
      K0. At a fixed pressure, for low pressures, the found equation reduces to a Vogel
      Fulcher-Tammann equation of tau versus temperature with the fragility parameter
      independent from pressure. The equation for tau(T,P) was successfully tested
      directly by fitting the dielectric relaxation time data for two isothermal and
      one isobaric measurements on diglycidyl ether of bisphenol-A, carried out in
      previous experiments. The parameters estimated by the best fit were in reasonable
      agreement with the values determined from the known physical properties of the
      material. Finally, the expression for the change versus pressure of the
      temperatures at which the same value of tau(max) is obtained (e.g., the change
      versus pressure of the glass transition temperature) agrees with several
      expressions previously proposed in the literature to provide a phenomenological
      description of the observed phenomena.

PMID- 11308643
TI  - Grain dynamics in a two-dimensional granular flow.
AB  - We have used particle tracking methods to study the dynamics of individual balls
      comprising a granular flow in a small-angle two-dimensional funnel. We
      statistically analyze many ball trajectories to examine the mechanisms of shock
      propagation. In particular, we study the creation of, and interactions between,
      shock waves. We also investigate the role of granular temperature and draw
      parallels to traffic flow dynamics.

PMID- 11308644
TI  - Effect of applied interparticle force on the static and dynamic angles of repose
      of spherical granular material.
AB  - The static angle of repose for iron spheres in a narrow box, and the dynamic
      angle of repose for iron spheres in a narrow, half-filled rotating drum is
      investigated. A feature of this paper is the use of a homogenous magnetic field
      to induce an attractive interparticle force, allowing a wide range of angles of
      repose to be investigated and characterized as a function of interparticle force.
      The static and dynamic angles of repose were found to increase approximately
      linearly with increasing interparticle force.

PMID- 11308645
TI  - Nonlinear hydrodynamical approach to granular materials.
AB  - We propose a nonlinear hydrodynamical model of granular materials. We show how
      this model describes the formation of a sandpile from a homogeneous distribution
      of material under gravity, and then discuss a simulation of a rotating sandpile
      which shows, in qualitative agreement with experiment, a static and dynamic angle
      of repose.

PMID- 11308646
TI  - Dissipative properties and scaling law for a layer of granular material on a
      vibrating plate.
AB  - The dissipative properties and scaling law for a layer of vertically vibrated
      granular materials were investigated by means of a dynamical model of a single
      sphere colliding completely inelastically with a massive, oscillating plate. A
      relationship is presented of how the temperature of the layer scales with the
      acceleration of the plate and the restitution coefficient of the grains. The
      numerical calculation shows the existence of an "energy well" and a "temperature
      well," which could be used to explain the existence of a f/2 flat (where f is the
      external driving frequency) state in an experiment on vibrated granular material.

PMID- 11308647
TI  - Selection of velocity profile and flow depth in granular flows.
AB  - The dynamics of a two-dimensional pile constituted by spherical grains organized
      in parallel layers is investigated theoretically. Only three effects are taken
      into account in the model: driving by gravity, nonlocal dissipation due to
      shocks, and trapping of grains by the bumps of the underneath layer. This is
      sufficient to recover the basic properties of granular avalanches: the transition
      between static and flowing state is hysteretic; the pile does not flow on the
      whole height but only in a layer at the surface; the velocity profile inside the
      flowing layer is approximately linear and is followed by a creep motion in the
      (quasi) static part. The flow height increases as a function of the pile angle
      and tends to infinity for a critical angle straight phi(infinity). The dependence
      of this critical angle with the static angle straight phi(s), the restitution
      coefficient rho, and the moment of inertia J, is investigated.

PMID- 11308648
TI  - Growth kinetics and structure of fibrin gels.
AB  - The structure and kinetics of fibrin gels grown from fibrinogen solutions under
      quasiphysiological conditions, but in absence of Ca++, were investigated by means
      of elastic light scattering. By combining classical light scattering and low
      angle elastic light scattering, an overall wave-vector range of about three
      decades was spanned, from q approximately 3 x 10(2) to q approximately 3 x 10(5)
      cm(-1). The scattered intensity distribution of the gels was measured in absolute
      units and fitted to a single function, which was able to reproduce accurately the
      data over the entire wave-vector range. From the fitting, it was possible to
      estimate the average diameter d of the fibrin fibers, the average crossover
      length xi of the gel, and establish the fractal nature of the gel structure, with
      a measure of its fractal dimension D(m). The measure of the intensity in absolute
      units also allowed the estimate of the density rho of the fibrin fibers and
      provided an independent measure of their size. The kinetics of formation of the
      gel was described in terms of a simple growth model: the scaffold of the network
      is formed very early in the course of the gelation process, at a "networking
      time," t(n), which is much smaller than the time required to form the final gel.
      At times t>t(n), the gel structure remains substantially unchanged and the
      successive growth consists only in a thickening of the gel fibers. Gels prepared
      under the same physical-chemical conditions, but at different fibrinogen
      concentrations, exhibited rather similar structures and kinetics, showing that
      the modalities of the gelation process are mainly governed by the solution
      conditions, and only secondarily by the fibrinogen concentration. For gels at
      fibrinogen concentration of approximately 0.24 mg/ml, the gel parameters were d
      approximately 130 nm, xi approximately 27 microm, D(m) approximately 1.3, and rho
      approximately 0.4 g/cm(3). Our d and rho values are in very good agreement with
      electron microscopy- and turbidity-derived literature data, respectively, while
      xi seems to be related to the mesh size of the initial scaffold formed at t(n),
      rather than to the mesh size of the final aged gel.

PMID- 11308649
TI  - Dynamic susceptibilities of an assembly of dipolar particles in an elastic
      environment.
AB  - Theoretical model to describe magnetodynamics of a ferrogel, i.e., an assembly of
      ferromagnetic nanoparticles embedded in a gel, is proposed. The reorientations of
      the particles are determined by the influence of the elastic matrix and the
      rotational Brownian motion. Due to the interplay between these two factors, the
      main parameter characterizing the static magnetic susceptibility of the system is
      the ratio of the elastic modulus of the matrix times particle volume to the
      thermal energy. It is shown that the main components of the dynamic magnetic
      susceptibility tensor are determined by the combinations of the reference rates
      of several processes inherent to the system, namely, the elastic restoration of
      the particle orientation, Brownian rotary diffusion, and viscous relaxation of
      the particle angular momentum. In the framework of the model, absorption of the
      energy of an alternating external field by a ferrogel is studied. With allowance
      for the ever present interaction of elastic and Brownian forces, the effective
      relaxation times for the longitudinal and transverse components of the ferrogel
      magnetization are evaluated.

PMID- 11308650
TI  - Phase coexistence in colloidal suspensions: an analytic Poisson-Boltzmann
      treatment.
AB  - We solve the linearized Poisson-Boltzmann equation analytically, subject to
      justifiable approximations, for a suspension containing a large number of
      identical spherical macroions under conditions of constant surface charge and
      zero added salt, in order to investigate the phase behavior of charge-stabilized
      colloidal suspensions. Our results for the electrostatic part of the Helmholtz
      free energy lead to an interaction which resembles the intermolecular interaction
      in the theory of molecular fluids. When combined with the ideal gas free energy
      of the counterions, this produces a van der Waals loop in the pV diagram,
      indicating coexistence between phases with different densities, for certain
      values of the macroion radius and charge. We also derive an expression for the
      surface potential of the macroions, and clarify the interpretation of the Poisson
      Boltzmann equation.

PMID- 11308651
TI  - Mechanical properties of a model of attractive colloidal solutions.
AB  - We review the nature of glass transitions and the glasses arising from a square
      well potential with a narrow and deep well. Our discussion is based on the mode
      coupling theory (MCT), and the predictions of glasses that we make refer to the
      "ideal" glasses predicted by this theory. We believe that the square-well system
      well represents colloidal particles with attractive interactions produced by
      grafted polymers, or depletion interactions. It has been recently shown that two
      types of glasses, an attractive and a repulsive one, are predicted by MCT for
      this model. The former can form at quite low densities. Most of our attention is
      directed at the mechanical properties of the glasses predicted by this theory. In
      particular we calculate the elastic shear modulus at zero frequency and the
      longitudinal stress modulus in the long wavelength limit. Results for both are
      presented along the glass-liquid transition curves and their interesting behavior
      is explained in terms of the underlying physics of the system.

PMID- 11308652
TI  - Tube diameter in tightly entangled solutions of semiflexible polymers.
AB  - A statistical mechanical treatment is given of the confinement of a wormlike
      polymer in an entangled solution to a tube, yielding quantitative predictions for
      the average tube diameter D(e) and macroscopic plateau modulus G, in the tightly
      entangled regime in which D(e) is much less than the persistence length L(p).
      Three approaches are pursued. A self-consistent binary collision approximation,
      which explicitly describes the topological constraints imposed by neighboring
      chains, yields predictions consistent with the scaling laws D(e)proportional to
      rho(-3/5) and G proportional to rho(7/5) proposed previously, where rho is the
      contour length per unit volume. An effective medium approximation, which treats
      the network as a continuum with a modulus G, instead yields D(e) proportional to
      rho(-1/3) and G proportional to rho(4/3), which is found to be the correct
      scaling in the limit rhoL(2)(p)>>1. An elastic network approximation treats the
      displacement of a test chain as the sum of a collective displacement of the
      network, which is treated as a continuum, plus a local displacement, which is
      treated in a binary collision approximation. Predictions are compared to
      measurements of both D(e) and G in actin protein filament (F-actin) solutions.

PMID- 11308653
TI  - Novel phases and reentrant melting of two-dimensional colloidal crystals.
AB  - We investigate two-dimensional (2D) melting in the presence of a one-dimensional
      (1D) periodic potential as, for example, realized in recent experiments on 2D
      colloids subjected to two interfering laser beams. The topology of the phase
      diagram is found to depend primarily on two factors: the relative orientation of
      the 2D crystal and the periodic potential troughs, which selects a set of Bragg
      planes running parallel to the troughs, and the commensurability ratio p=a(')/d
      of the spacing a(') between these Bragg planes to the period d of the periodic
      potential. The complexity of the phase diagram increases with the magnitude of
      the commensurabilty ratio p. Rich phase diagrams, with "modulated liquid,"
      "floating," and "locked floating" solid and smectic phases are found. Phase
      transitions between these phases fall into two broad universality classes,
      roughening and melting, driven by the proliferation of discommensuration walls
      and dislocations, respectively. We discuss correlation functions and the static
      structure factor in these phases, and make detailed predictions about the
      universal features close to the phase boundaries. We predict that for charged
      systems with highly screened short-range interactions, these melting transitions
      are generically reentrant as a function of the strength of the periodic
      potential, a prediction that is in accord with recent 2D colloid experiments.
      Implications of our results for future experiments are also discussed.

PMID- 11308654
TI  - Phase-field modeling of microstructural pattern formation during directional
      solidification of peritectic alloys without morphological instability.
AB  - During the directional solidification of peritectic alloys, two stable solid
      phases (parent and peritectic) grow competitively into a metastable liquid phase
      of larger impurity content than either solid phase. When the parent or both solid
      phases are morphologically unstable, i.e., for a small temperature
      gradient/growth rate ratio (G/v(p)), one solid phase usually outgrows and covers
      the other phase, leading to a cellular-dendritic array structure closely
      analogous to the one formed during monophase solidification of a dilute binary
      alloy. In contrast, when G/v(p) is large enough for both phases to be
      morphologically stable, the formation of the microstructure becomes controlled by
      a subtle interplay between the nucleation and growth of the two solid phases. The
      structures that have been observed in this regime (in small samples where
      convection effects are suppressed) include alternate layers (bands) of the parent
      and peritectic phases perpendicular to the growth direction, which are formed by
      alternate nucleation and lateral spreading of one phase onto the other as
      proposed in a recent model [R. Trivedi, Metall. Mater. Trans. A 26, 1 (1995)], as
      well as partially filled bands (islands), where the peritectic phase does not
      fully cover the parent phase which grows continuously. We develop a phase-field
      model of peritectic solidification that incorporates nucleation processes in
      order to explore the formation of these structures. Simulations of this model
      shed light on the morphology transition from islands to bands, the dynamics of
      spreading of the peritectic phase on the parent phase following nucleation, which
      turns out to be characterized by a remarkably constant acceleration, and the
      types of growth morphology that one might expect to observe in large samples
      under purely diffusive growth conditions.

PMID- 11308655
TI  - Rheological and small-angle neutron scattering studies of aqueous solutions of
      branched PEO-PPO-PEO copolymers.
AB  - Tetronic 908 is a four-branched copolymer comprised of polyethylene oxide (PEO)
      and polypropylene oxide (PPO) blocks fixed on an aliphatic diamine. In aqueous
      solution, this polymer has an amphiphilic character due to the difference in PEO
      and PPO solubilities with increase in temperature. This system presents
      interesting rheological properties depending on the polymer concentration in
      solution and temperature. At low temperatures and/or concentrations, the solution
      behaves as a Newtonian fluid. For a weight percentage p comprised between 2% and
      22%, the viscosity of the solution goes through a maximum. Small-angle neutron
      scattering experiments show that the increase in viscosity is due to progressive
      aggregation of chains. For weight percentages higher than p=22%, the viscosity of
      the system diverges and the mixture becomes gel-like. In fact, spectromechanical
      measurements show that the solution behaves as an entangled polymer with a high
      relaxation time in the flow zone. Small-angle neutron scattering (SANS) studies
      of the same solution reveal the presence of several peaks indicating that the
      micelles are organized in a cubic structure. We have developed a model that
      suitably describes the SANS curves of this system in the region where micelles
      are formed. Our model considers that micelles are trilayered spherical entities
      that coexist with unimers by obeying an equilibrium reaction. Moreover, it allows
      the calculation of several parameters such as the volume fraction of micelles,
      their size, and composition. The evolution of these parameters with temperature
      and polymer concentration is detailed. Comparisons with literature models are
      presented and discussed. This compilation of results has permitted the
      establishment of precise relations between the structure of this polymer in
      solution and its rheological properties.

PMID- 11308656
TI  - Line tension approaching a first-order wetting transition: experimental results
      from contact angle measurements.
AB  - The line tension values of n-octane and 1-octene on a hexadecyltrichlorosilane
      coated silicon wafer, are determined by contact angle measurements at
      temperatures near a first-order wetting transition T(w). It is shown
      experimentally that the line tension changes sign as the temperature increases
      toward T(w) in agreement with a number of theoretical predictions. A simple
      phenomenological model possessing a repulsive barrier at l(0)=5.1+/-0.2 nm and a
      scale factor of B=78+/-6 provides a quantitative description of the experiments.

PMID- 11308657
TI  - Interfacial fluctuations near the critical filling transition.
AB  - We advance a method to describe the short-distance fluctuations of an interface
      spanning a wedge-shaped substrate near the critical filling transition. Two
      different length scales determined by the average distance of the interface from
      the substrate at the wedge center can be identified. On one length scale, the one
      dimensional approximation of A. O. Parry, C. Rascon, and A. J. Wood [Phys. Rev.
      Lett. 85, 345 (2000)], which allows one to determine the interfacial critical
      exponents, is extracted from the full description. On the other scale, the short
      distance fluctuations are analyzed by mean-field theory.

PMID- 11308658
TI  - Coiling instability of multilamellar membrane tubes with anchored polymers.
AB  - We study experimentally a coiling instability of cylindrical multilamellar stacks
      of phospholipid membranes, induced by polymers with hydrophobic anchors grafted
      along their hydrophilic backbone. Our system is unique in that coils form in the
      absence of both twist and adhesion. We interpret our experimental results in
      terms of a model in which local membrane curvature and polymer concentration are
      coupled. The model predicts the occurrence of maximally tight coils above a
      threshold polymer occupancy. A proper comparison between the model and experiment
      involved imaging of projections from simulated coiled tubes with maximal
      curvature and complicated torsions.

PMID- 11308659
TI  - Numerical study of the Marangoni instability resulting in surface tension auto
      oscillations: general regularities of the system evolution.
AB  - Theoretical studies are performed to explain the mechanism of surface tension
      auto-oscillations recently found. The Marangoni instability in a system
      containing a surfactant droplet under the air-water interface is investigated
      numerically. The simulations, based on the equations of fluid mechanics, take
      into account convective diffusion and adsorption of the surfactant. The behavior
      of the system is determined by nonstationary concentration gradients that are
      nonuniform on the surface as well as in the normal to the surface direction.
      Initially a slow diffusion dissolution of the drop material takes place. The
      convective transfer of the surfactant is negligible, the surface tension remains
      nearly constant and the system parameters change rather slowly during the
      induction period. With the increase of the concentration gradients the system
      becomes unstable, resulting in a jump in the convection velocity, surface
      tension, and adsorption on the surface. The concentration and velocity
      distributions in the bulk and on the surface are obtained from the numerical
      solution of the problem. The contributions of different mechanisms of the mass
      transfer are compared in different stages of the process.

PMID- 11308660
TI  - Formation and distribution of point defects on a disclination line near a free
      nematic interface.
AB  - Point defects of opposite signs can alternately nucleate on the -1/2 disclination
      line that forms near the free surface of a confined nematic liquid crystal. We
      show the existence of metastable configurations consisting of periodic
      repetitions of such defects. These configurations are characterized by a minimal
      interdefect spacing that is seen to depend on sample thickness and on an applied
      electric field. The time evolution of the defect distribution suggests that the
      defects attract at small distances and repel at large distances.

PMID- 11308661
TI  - Interactions between colloidal inclusions in two-dimensional smectic-C* films.
AB  - We report an experimental study of colloidal inclusions in free-standing films of
      smectic-C* liquid crystal. The inclusions are cholesteric droplets that form
      above the bulk smectic-C*-7cholesteric transition temperature. Each droplet
      confined in a two-dimensional (2D) system, is accompanied by a topological
      defect. The distortions of the in-plane orientational order of the smectic-C*
      film induce elastic interactions between the droplets. As in 3D water nematic
      emulsions, a short-range repulsion and a long-range dipolar attraction govern the
      stability of the inclusions and lead to their organization in chainlike
      structures. Our results are in agreement with recent theoretical predictions.

PMID- 11308662
TI  - Influence of ions on the "V-shaped" electro-optic response of ferroelectric
      liquid crystals.
AB  - It has recently been shown that in surface-stabilized ferroelectric liquid
      crystal cells with high spontaneous polarization, the polarization charge self
      interaction leads to a "V-shaped" optical response to an applied voltage. The
      presence of ionic free charges in the liquid crystal changes the internal
      electric field, and therefore also the spatial dependence of the polarization and
      optic axis orientation. We have numerically solved the nonlinear ion diffusion
      equation in the electric field due to external voltage, spontaneous polarization,
      and ions, and calculated the electro-optic response to a triangular applied
      voltage. When the period of the driving voltage is smaller than the zero-field
      diffusion time of the ions across the cell, and larger than the ion transit time
      in the applied field, an inverse hysteresis in the electro-optic response is
      obtained. At these time scales ions also cause characteristic changes in the
      shape of the electro-optic response.

PMID- 11308663
TI  - Landau-de Gennes theory of surface-enhanced ordering in smectic films.
AB  - A Landau theory for surface-enhanced ordering in smectic-A free-standing films is
      described, based on a generalization of de Gennes' model for a "presmectic" fluid
      confined between two walls. According to the theory, smectic ordering in free
      standing films heated above the bulk smectic melting temperature is due to an
      intrinsic surface contribution rather than an external field. The theory yields a
      persistent finite-size effect, in that the film melting temperatures do not tend
      to the bulk transition temperature in the limit of infinite film thickness. It
      also predicts that a continuous transition from (N+1)- to N-layer films is
      impossible without an external field. The theory closely fits existing
      experimental data on layer-thinning transitions in compounds which exhibit a bulk
      smectic-A to nematic phase transition. Possible origins of the intrinsic surface
      contribution are discussed.

PMID- 11308664
TI  - Surface depinning of smectic-A edge dislocations.
AB  - Using a Landau-de Gennes approach, we model the formation of an edge dislocation
      in a smectic-A cell initially in the bookshelf structure. The driving force is
      the mismatch between the layer thickness in a bulk smectic-A liquid crystal and
      that imposed by confining plates. The core structure of the dislocation is
      calculated taking into account spatial variations of the smectic translational
      order parameter. We numerically determine the critical condition for the surface
      driven formation and depinning of the dislocation. By exploiting this phenomenon,
      we show how the value of the positional anchoring strength at the surface can be
      determined.

PMID- 11308665
TI  - Dynamics of free-standing smectic-A films.
AB  - The eigenvibrations and time-dependent layer displacement-layer displacement
      correlation functions are analyzed in a free-standing thin smectic-A films with
      the help of a discrete layer model. The film motions are described using the
      Chebyshev polynomials of second kind, U(n)(x). The eigenfrequencies problem is
      essentially simplified within the framework of this approach since the numerical
      solution of the high degree algebraic characteristic equation is replaced by the
      analytical solution of a rather simple trigonometrical equation. The dependences
      of eigenmodes on wave number q(perpendicular) were analyzed. For small
      q(perpendicular) one mode is a low frequency acoustic wave and other modes are
      high frequency optical oscillations. As the wave number q(perpendicular)
      increases all modes successively turn into relaxation when starting with the
      acoustic mode. The rather simple expression for susceptibility matrix and for
      spectral densities of layer displacement correlation functions were obtained
      using the Chebyshev polynomials. It was shown that the frequency dependences of
      spectral densities are sensitive to wave number q(perpendicular). For small
      q(perpendicular) the spectral densities of displacement-displacement correlation
      functions have a sharp peak and for large q(perpendicular) they turn into a
      contours of Lorentzian type.

PMID- 11308666
TI  - Time-resolved infrared spectroscopy of nematic-liquid-crystal electro-optic
      switching.
AB  - Time resolved infrared (IR) vibrational absorption spectroscopy is used to probe
      the dynamics of electric field-induced reorientation of the biphenyl molecular
      core and alkyl tail subfragments of the nematic liquid crystal 5CB (4-pentyl-4
      cyanobiphenyl). The planar to homeotropic transition, induced by application of
      an electric field step to high pre-tilt planar aligned cells, is studied for
      switching times ranging from 200 micros down to 8 micros, the latter a factor of
      1000 times faster than any previous nematic IR study. The reorientation rates of
      the core and tail are found to be the same to within experimental uncertainty,
      and scale inversely with applied field squared, as expected for the balance of
      field and viscous torques. Thus any molecular conformation change during
      switching must relax on a shorter time scale. A simple model shows that these
      data eliminate the possibility of there being substantial differences between the
      reorientational dynamics of the tails and cores on the time scales longer than on
      the order of 10 micros.

PMID- 11308667
TI  - Fluctuation-entanglement mechanism for director anchoring at nematic polymer
      surfaces.
AB  - The existence of polymeric entanglements in a polymer nematic liquid crystal
      modifies the Frank elastic description governing director deformation. We present
      a calculation of the director fluctuation contribution to polymer nematic surface
      tension, in which we supplement the usual Frank terms with a damping term due to
      entanglements. We infer an effective surface anchoring potential, going to zero
      as n ln n in the limit of low entanglement density n. The anchoring easy axis
      depends on the relative magnitudes of the Frank constants governing director
      elasticity. We comment on generalizing the approach to take into account
      polydomain structure.

PMID- 11308668
TI  - Molecular weight dependence of reductions in the glass transition temperature of
      thin, freely standing polymer films.
AB  - We have used transmission ellipsometry to perform a comprehensive study of the
      glass transition temperature T(g) of freely standing polystyrene films. Six
      molecular weights M(w), ranging from 575 x 10(3) to 9100 x 10(3), were used in
      the study. For each M(w) value, large reductions in T(g) (as much as 80 degrees C
      below the bulk value) were observed as the film thickness h was decreased. We
      have studied in detail the dependence of the T(g) reductions on M(w) in a regime
      dominated by chain confinement effects. The empirical analysis presented is
      highly suggestive of the existence of a mechanism of mobility in thin freely
      standing films that is inhibited in the bulk and distinct from the usual
      cooperative motion associated with the glass transition.

PMID- 11308669
TI  - Cold and warm swelling of hydrophobic polymers.
AB  - We introduce a polymer model where the transition from swollen to compact
      configurations is due to interactions between the monomers and the solvent. These
      interactions are the origin of the effective attractive interactions between
      hydrophobic amino acids in proteins. We find that in the low and high temperature
      phases polymers are swollen, and there is an intermediate phase where the most
      favorable configurations are compact. We argue that such a model captures in a
      single framework both the cold and the warm denaturation experimentally detected
      for thermosensitive polymers and for proteins.

PMID- 11308670
TI  - Chain aggregation in dilute solutions of poly(methyl methacrylate) below the
      phase-separation temperature.
AB  - For dilute solutions of poly(methyl methacrylate) in isoamyl acetate with the
      molecular weight M(w)=4.4 x 10(6), the phase-separation process was studied by
      static light-scattering measurements. The dilute solutions in the concentration
      range from 1.4 x 10(-4) to 3.8 x 10(-4) g/cm(3) were quenched to about 16 K below
      the phase-separation temperature, and the aggregation processes of polymer chains
      were measured over a period of several hours. By analyzing the light-scattering
      data with the Guinier plot, the weight-averaged molecular weight <M>(w) and z
      averaged square radius <R2>(1/2)(z) for clusters of polymer chains were
      determined as a function of time t(min) and concentration c (g/cm(3)). The growth
      of clusters was represented by the exponential forms <M>(w)/M(0)=e(gct) and
      <R2>(z)/R(2)(0)=e(hct) as a function of ct, where M(0) and R2(0) were the values
      at t=0, and the constants g and h were determined to be g=11.6 and h=7.5. A
      double-logarithmic plot of <M>(w) versus <R2>(1/2)(z) yielded a straight line
      with the slope D=3.06+/-0.02. These characteristic features of the chain
      aggregation process were compared with the Smoluchowski equation for cluster
      cluster aggregation with the collision kernel (i+j) for i-mer and j-mer. The
      observed slow growth of clusters was attributed to the reaction- limited cluster
      aggregation. The chain density in a cluster was found to increase with an
      increase of the cluster size, resulting in the slope D exceeding 3.

PMID- 11308671
TI  - Monte Carlo simulation of morphologies of self-assembled amphiphilic diblock
      copolymers in solution.
AB  - The Monte Carlo method has been applied to simulate the process of the self
      assembling of amphiphilic diblock copolymers in a selective solvent. The
      simulations illustrated that the aggregates morphologies of A-b-B diblock
      copolymers in solution strongly depend on the length of corona-forming segments,
      i.e., with the decrease of the corona-forming segments, the transition of
      spherical micelles to rodlike aggregates occurs, which are in accord with the
      experimental results of Eisenberg and co-workers [Science 268, 1728 (1995);
      Macromolecules 32, 2239 (1999); 31, 3509 (1998); 29, 6359 (1996); 31, 9399
      (1998)].

PMID- 11308672
TI  - Exactness of the annealed and the replica symmetric approximations for random
      heteropolymers.
AB  - We study a heteropolymer model with random contact interactions introduced some
      time ago as a simplified model for proteins. The model consists of self-avoiding
      walks on the simple cubic lattice, with contact interactions between nearest
      neighbor pairs. For each pair, the interaction energy is an independent Gaussian
      variable with mean value B and variance Delta(2). For this model the annealed
      approximation is expected to become exact for low disorder, at sufficiently high
      dimension and in the thermodynamic limit. We show that corrections to the
      annealed approximation in the three-dimensional high-temperature phase are small,
      but do not vanish in the thermodynamic limit, and are in good agreement with our
      replica symmetric calculations. Such corrections derive from the fact that the
      overlap between two typical chains is nonzero. We explain why previous authors
      had come to the opposite conclusion, and discuss consequences for the
      thermodynamics of the model. Numerical results were obtained by simulating chains
      of length N<or=1400 by means of the recent PERM algorithm, in the coil and molten
      globular phases, well above the freezing temperature.

PMID- 11308673
TI  - Shot noise in the leaky integrate-and-fire neuron.
AB  - We study the influence of noise on the transmission of temporal information by a
      leaky integrate-and-fire neuron using the theory of shot noise. The model
      includes a finite number of synapses and has a membrane potential variance de
      facto modulated by the input signal. The phenomenon of stochastic resonance in
      spiking neurons is analytically exhibited using an inhomogeneous Poisson process
      model of the spike trains, and links with the traditional Ornstein-Uhlenbeck
      process obtained by a diffusion approximation are given. It is shown that the
      modulated membrane potential variance inherent to the model gives better signal
      processing capabilities than the diffusion approximation.

PMID- 11308674
TI  - Population dynamics with and without selection.
AB  - A model describing population dynamics is presented. We study the effect of
      selection pressure and inbreeding on the time evolution of the population and the
      chances of survival. We find that the selection is in general beneficial,
      enabling survival of a population whose size is declining. Inbreeding reduces the
      survival chances since it leads to clustering of individuals. We have also found,
      in agreement with biological data, that there is a threshold value of the initial
      size of the population, as well as of the habitat, below which the population
      will almost certainly become extinct. We present analytical and computer
      simulation approaches.

PMID- 11308675
TI  - Long-range intermolecular interaction between broken DNA fragments.
AB  - We analyzed the long-range intermolecular interaction between fragments of broken
      DNA. We considered two constituents of long-range intermolecular interaction. The
      first is a net electrostatic Coulomb interaction between charges, involved in a
      structure of opposite nucleotides, which we evaluate using Debye-Huckel theory.
      The second one is the Van der Waals interaction between the nucleotides. The
      general Lifshitz theory of Van der Waals forces was used to evaluate this
      interaction. Numerical calculations showed that a repulsive force between broken
      DNA fragments can arise in specific cases. This repulsion can prevent DNA from
      repairing itself after a double-strand break. The height of the barrier decreases
      with an increase of the ionic strength of the intracellular milieu, or with a
      reduction of its viscosity.

PMID- 11308676
TI  - Coexistence of multiple spiral waves with independent frequencies in a
      heterogeneous excitable medium.
AB  - We studied the interactions and coexistence of stable spiral waves with
      independent frequencies in a heterogeneous excitable medium, using numerical
      simulations of a spatial system based on the FitzHugh-Nagumo cell model. When the
      heterogeneity of the medium exceeded a critical value, a transition took place
      from a single dominant spiral wave to a coexistence of multiple spiral waves with
      independent frequencies and n:n-1 wave conduction blocks. In this case, multiple
      spiral waves could coexist because they are "insulated" from each other by
      chaotic regions.

PMID- 11308677
TI  - Global dynamics and stochastic resonance of the forced FitzHugh-Nagumo neuron
      model.
AB  - We have analyzed the responses of an excitable FitzHugh-Nagumo neuron model to a
      weak periodic signal with and without noise. In contrast to previous studies
      which have dealt with stochastic resonance in the excitable model when the model
      with periodic input has only one stable attractor, we have focused our attention
      on the relationship between the global dynamics of the forced excitable neuron
      model and stochastic resonance. Our results show that for some parameters the
      forced FitzHugh-Nagumo neuron model has two attractors: the small-amplitude
      subthreshold periodic oscillation and the large-amplitude suprathreshold periodic
      oscillation. Random transitions between these two periodic oscillations are the
      essential mechanism underlying stochastic resonance in this model. Differences of
      such stochastic resonance to that in a classical bistable system and the
      excitable system are discussed. We also report that the state of the basin of
      attraction has a significant effect on the stability of neuronal firings, in the
      sense that the fractal basin boundary of the system enhances the noise-induced
      transitions.

PMID- 11308678
TI  - Effects of correlated and independent noise on signal processing in neuronal
      systems.
AB  - Stochastic resonance has recently received considerable attention demonstrating
      that noise can play a constructive role in signal processing. We investigate the
      effects of input noise on sensory processing via numerical simulation when they
      are independent of each other or spatially correlated in a globally coupled
      neuronal network. The network exhibits a coherent behavior in the absence of
      stimulation. Such ongoing activity has a remarkable influence on neuronal
      responses to stimuli. In the presence of a subthreshold periodic signal, the
      activity averaged over neurons can convey precise information about the stimulus
      in the case of independent noise. On the other hand, when the noise is correlated
      among the neurons, the average response is nearly as noisy and variable as the
      responses of the individual neurons. Thus, the spatially correlated noise
      diminishes the beneficial effects of pooling, although it can evoke synchronous
      firings of neurons. These suggest that response variability in cortical activity
      may be closely related to the correlation in input noise.

PMID- 11308679
TI  - Analytic model for ring pattern formation by bacterial swarmers.
AB  - We analyze a model proposed by Medvedev, Kaper, and Kopell (the MKK model) for
      ring formation in two-dimensional bacterial colonies of Proteus mirabilis. We
      correct the model to formally include a feature crucial of the ring generation
      mechanism: a bacterial density threshold to the nonlinear diffusivity of the MKK
      model. We numerically integrate the model equations, and observe the logarithmic
      profiles of the bacterial densities near the front. These lead us to define a
      consolidation front distinct from the colony radius. We find that this
      consolidation front propagates outward toward the colony radius with a nearly
      constant velocity. We then implement the corrected MKK equations in two
      dimensions and compare our results with biological experiment. Our numerical
      results indicate that the two-dimensional corrected MKK model yields smooth
      (rather than branched) rings, and that colliding colonies merge if grown in phase
      but not if grown out of phase. We also introduce a model, based on coupling the
      MKK model to a nutrient field, for simulating experimentally observed branched
      rings.

PMID- 11308680
TI  - Kinetic proofreading can explain the supression of supercoiling of circular DNA
      molecules by type-II topoisomerases.
AB  - The enzymes that pass DNA through DNA so as to remove entanglements, adenosine
      triphosphate-hydrolyzing type-II topoisomerases, are able to suppress the
      probability of self-entanglements (knots) and mutual entanglements (links)
      between approximately 10 kb plasmids, well below the levels expected, given the
      assumption that the topoisomerases pass DNA segments at random by thermal motion.
      This implies that a 10-nm type-II topoisomerase can somehow sense the topology of
      a large DNA. We previously introduced a "kinetic proofreading" model which
      supposes the enzyme to require two successive collisions in order to allow
      exchange of DNA segments, and we showed how it could quantitatively explain the
      reduction in knotting and linking complexity. Here we show how the same model
      quantitatively explains the reduced variance of the double-helix linking number
      (supercoiling) distribution observed experimentally.

PMID- 11308681
TI  - Behavioral stochastic resonance: how a noisy army betrays its outpost.
AB  - Juvenile paddlefish prey upon single zooplankton by detecting a weak electric
      signature resulting from its feeding and swimming motions. Moreover, it has
      recently been shown that paddlefish make use of stochastic resonance near the
      threshold for prey detection: a process termed behavioral stochastic resonance.
      But this process depends upon an external source of electric noise. A swarm of
      plankton, for example, Daphnia, can provide this noise. Assuming that juvenile
      paddlefish attack single Daphnia as outliers in the vicinity of the swarm, making
      use of noise from the swarm, we calculate the spatial distribution of the average
      phase locking period for the subthreshold signals acting at the paddlefish
      rostrum. Numeric evaluation of analytic formulas supports the notion of a noise
      induced widening of the capture area quantitatively.

PMID- 11308682
TI  - Dynamics of moments of FitzHugh-Nagumo neuronal models and stochastic
      bifurcations.
AB  - For the study of the behavior of noisy neuronal models, Rodriguez and Tuckwell
      have introduced an elegant and systematic method which consists of replacing the
      system of stochastic differential equations with a system of deterministic
      equations representing the dynamics of the means, variances, and covariance of
      the state variables [R. Rodriguez and H.C. Tuckwell, Phys. Rev. E 54, 5585
      (1996)]. In this work, we first report a modification of their method in the case
      of the FitzHugh-Nagumo model which enhances the accuracy of the approximation
      without including higher order moments. This method is then combined with a self
      consistency argument in order to better characterize the behavior of the
      underlying stochastic processes through the computation of approximate auto- and
      cross-correlation functions of the state variables. Finally, we argue that the
      moments' equations can also reveal the existence of stochastic bifurcations,
      i.e., qualitative changes in the dynamics of stochastic systems.

PMID- 11308683
TI  - Adaptive learning by extremal dynamics and negative feedback.
AB  - We describe a mechanism for biological learning and adaptation based on two
      simple principles: (i) Neuronal activity propagates only through the network's
      strongest synaptic connections (extremal dynamics), and (ii) the strengths of
      active synapses are reduced if mistakes are made, otherwise no changes occur
      (negative feedback). The balancing of those two tendencies typically shapes a
      synaptic landscape with configurations which are barely stable, and therefore
      highly flexible. This allows for swift adaptation to new situations. Recollection
      of past successes is achieved by punishing synapses which have once participated
      in activity associated with successful outputs much less than neurons that have
      never been successful. Despite its simplicity, the model can readily learn to
      solve complicated nonlinear tasks, even in the presence of noise. In particular,
      the learning time for the benchmark parity problem scales algebraically with the
      problem size N, with an exponent k approximately 1.4.

PMID- 11308684
TI  - Difference between "proteinlike" and "nonproteinlike" heteropolymers.
AB  - Based on a simple two-dimensional (2D) hydrophobic-polar (H-P) lattice model,
      properties of amino acid chains are studied by enumeration and Monte-Carlo
      simulation methods. Among them some chains with large average energy gap (E(g);)
      are thought to be "proteinlike" while the others are "nonproteinlike." The large
      E(g); between the low excited conformations and the native conformation
      guarantees not only the thermodynamic stability of protein but also its fast
      folding property. The phase transition from molten globule to the native
      conformation for the "proteinlike" polymer is found to be of first order, while
      that for the "nonproteinlike" polymer is not. Some properties of chains as a
      function of E(g); shows that the transition from "nonproteinlike" to
      "proteinlike" heteropolymers is continuous. The simulation of folding at
      different temperature indicates that the main reason why some polymers fold
      slowly to its native conformation is their low folding temperature which makes
      the effective energy barrier (E(b)/T(f)) much higher than "proteinlike" chains.

PMID- 11308685
TI  - Noise-induced transport of two coupled particles.
AB  - We study the motion of two harmonically coupled particles in a sawtooth
      potential. The particles are subject to temporally correlated multiplicative
      noise. The stationary current is calculated in an expansion about the limit of
      rigid coupling. For two coupled particles a driving mechanism occurs which is
      different from the one occurring in the case of a single particle. In particular
      this mechanism does not need diffusion. Depending on the equilibrium distance of
      the particles and the coupling constant, a current reversal occurs. Possible
      relevance as a model for motor proteins is discussed.

PMID- 11308686
TI  - Theory of periodic swarming of bacteria: application to Proteus mirabilis.
AB  - The periodic swarming of bacteria is one of the simplest examples for pattern
      formation produced by the self-organized collective behavior of a large number of
      organisms. In the spectacular colonies of Proteus mirabilis (the most common
      species exhibiting this type of growth), a series of concentric rings are
      developed as the bacteria multiply and swarm following a scenario that
      periodically repeats itself. We have developed a theoretical description for this
      process in order to obtain a deeper insight into some of the typical processes
      governing the phenomena in systems of many interacting living units. Our approach
      is based on simple assumptions directly related to the latest experimental
      observations on colony formation under various conditions. The corresponding one
      dimensional model consists of two coupled differential equations investigated
      here both by numerical integrations and by analyzing the various expressions
      obtained from these equations using a few natural assumptions about the
      parameters of the model. We determine the phase diagram corresponding to systems
      exhibiting periodic swarming, and discuss in detail how the various stages of the
      colony development can be interpreted in our framework. We point out that all of
      our theoretical results are in excellent agreement with the complete set of
      available observations. Thus the present study represents one of the few examples
      where self-organized biological pattern formation is understood within a
      relatively simple theoretical approach, leading to results and predictions fully
      compatible with experiments.

PMID- 11308687
TI  - Stochastic resonance in neuron models: endogenous stimulation revisited.
AB  - The paradigm of stochastic resonance (SR)-the idea that signal detection and
      transmission may benefit from noise-has met with great interest in both physics
      and the neurosciences. We investigate here the consequences of reducing the
      dynamics of a periodically driven neuron to a renewal process (stimulation with
      reset or endogenous stimulation). This greatly simplifies the mathematical
      analysis, but we show that stochastic resonance as reported earlier occurs in
      this model only as a consequence of the reduced dynamics.

PMID- 11308688
TI  - Nonequilibrium roughening transition in a volume conserving system.
AB  - We introduce a simple volume conserving stochastic model undergoing a
      nonequilibrium roughening transition (NRT) in 1+1 dimensions. In our model, there
      is no deposition and evaporation of a particle breaking the volume conserving
      condition. The degree of roughness of the fluctuating interface in our model is
      determined by whether or not the hopping of a particle depends on the local slope
      of the interface. The hopping process of a particle is controlled by the
      probability 0<or=p<or=1. For p<1/2, a moving particle tends to hop in the
      downhill direction of the local slope of the interface, and so the interface is
      in a smooth phase with a zero roughness exponent. For p>1/2, a particle tends to
      hop in the uphill direction, and so the interface cannot reach a saturated phase.
      When p=1/2, the hopping of a particle does not depend on the local slope of the
      interface. Then the interface can reach a saturated phase. The saturated
      interface at p=1/2 is in a rough phase with a nonzero roughness exponent. Our
      model, therefore, exhibits the NRT at the critical parameter p(c)=1/2.

PMID- 11308689
TI  - Liquid-solid phase transition of a system with two particles in a rectangular
      box.
AB  - We study the statistical properties of two hard spheres in a two-dimensional
      rectangular box. In this system, a relation similar to the van der Waals equation
      is obtained between the width of the box and the pressure working on the
      sidewalls. The autocorrelation function of each particle's position is calculated
      numerically. This calculation shows that, near the critical width, the time at
      which the correlation becomes zero gets longer as the height of the box
      increases. Moreover, fast and slow relaxation processes such as the alpha and
      beta relaxations in supercooled liquids are observed when the height of the box
      is sufficiently large. These relaxation processes are discussed with reference to
      the probability distribution of the relative positions of the two particles.

PMID- 11308690
TI  - Entropy fluctuations for directed polymers in 2+1 dimensions.
AB  - We find numerically that the sample to sample fluctuation of the entropy DeltaS
      is a more sensitive tool in distinguishing low from high temperature behaviors
      than the common corresponding fluctuation in the free energy. In 1+1 dimensions
      we find a single phase for all temperatures, since (DeltaS)(2) is always
      extensive. In 2+1 dimensions we find a behavior that at first sight might appear
      to be a transition from a low temperature phase where (DeltaS)(2) is extensive to
      a high temperature phase where it is subextensive. This is observed in spite of
      the relatively large system we use. The observed behavior is explained not as a
      phase transition but as a strong crossover behavior. We use an analytical
      argument to obtain (DeltaS)(2) for high temperature, and find that while it is
      always extensive it is also extremely small, and that the leading extensive part
      decays very quickly to zero as the temperature is increased.

PMID- 11308691
TI  - Positional order and thermal expansion of surface crystalline N-alkane
      monolayers.
AB  - We report a high-resolution synchrotron grazing incidence x-ray diffraction
      measurement of a surface crystalline monolayer at the liquid-vapor interface of
      the n-alkane eicosane (C20H42) just above its melting temperature. The peak width
      of the surface monolayer rotator phase is shown to be resolution limited and
      implies positional correlations of at least approximately 1 microm. The high
      resolution allowed determination of the temperature dependence of the peak
      position over the narrow (3 degrees C) temperature range of the surface crystal
      phase. The two-dimensional thermal expansion was determined to be
      (dA/dT)/A=1.8(+/-0.1)x10(-3) degrees C-1, which is comparable to the expansion in
      similar chain length bulk n-alkane rotator phases. Our data are consistent with
      the power-law shaped scattering tails expected from quasi-long-range order in two
      dimensions.

PMID- 11308692
TI  - Saddle-splay elasticity and interfacial nematostatics.
AB  - This Brief Report drives the generalized force balance equations of interfacial
      statics between nematic liquid crystals (NLC) and isotropic fluids (I), using the
      classical equations of liquid crystal physics, taking into account an important
      class of gradient surface elasticity, known as saddle-splay elasticity. The
      objective is to identify the exact nature of the saddle-splay contributions to
      the fundamental interfacial force balance equations, known as the Laplace-Young
      equation and the Marangoni force equation. General expressions for the dynamic
      generalization of these two equations were given by Shih, Mann, and Brown [Mol.
      Cryst. Liq. Cryst. 98, 47 (1983)], but the specific form of the static terms
      appearing in these two equations were missing in the literature, and are now
      given in this paper. It is found that the tensorial order and functional form of
      the contributions of saddle-splay elasticity to the two force balance equations
      are congruent with those arising from the interfacial tension. Therefore, to
      generalize the interfacial equations of nematostatics by including saddle-splay
      energy, the interfacial tension must be renormalized with the saddle-splay energy
      contribution. In addition, saddle splay gives rise to distortion stresses, the
      two-dimensional analog to the bulk Ericksen stresses, which contribute to the
      tangential Marangoni force. Exact expressions for pressure jumps across NLC/I
      interfaces and for the tangential Marangoni force are derived and analyzed. These
      generalized results are expected to be useful in the characterization of
      nematocapillarity phenomena, such as wetting, spreading, and the mechanics of
      thin nematic films.

PMID- 11308693
TI  - Thermodynamically important contacts in folding of model proteins.
AB  - We introduce a quantity, the entropic susceptibility, that measures the
      thermodynamic importance-for the folding transition-of the contacts between amino
      acids in model proteins. Using this quantity, we find that only one equilibrium
      run of a computer simulation of a model protein is sufficient to select a subset
      of contacts that give rise to the peak in the specific heat observed at the
      folding transition. To illustrate the method, we identify thermodynamically
      important contacts in a model 46-mer. We show that only about 50% of all contacts
      present in the protein native state are responsible for the sharp peak in the
      specific heat at the folding transition temperature, while the remaining 50% of
      contacts do not affect the specific heat.

PMID- 11308695
TI  - Corrections to scaling for the two-dimensional dynamic XY model.
AB  - With large-scale Monte Carlo simulations, we confirm that for the two-dimensional
      XY model, there is a logarithmic correction to scaling in the dynamic relaxation
      starting from a completely disordered state, while only an inverse power law
      correction in the case of starting from an ordered state. The dynamic exponent z
      is z=2.04(1).

PMID- 11308696
TI  - Chaotic motion around prolate deformed bodies.
AB  - The motion of particles in the field of forces associated to an axially symmetric
      attraction center modeled by a monopolar term plus a prolate quadrupole
      deformations is studied using Poincare surface of sections and Lyapunov
      characteristic numbers. We find chaotic motion for certain values of the
      parameters, and that the instability of the orbits increases when the quadrupole
      parameter increases. A general relativistic analog is briefly discussed.

PMID- 11308697
TI  - Reducing nonideal to ideal coupling in random matrix description of chaotic
      scattering: application to the time-delay problem.
AB  - We write explicitly a transformation of the scattering phases reducing the
      problem of quantum chaotic scattering for systems with M statistically equivalent
      channels at nonideal coupling to that for ideal coupling. Unfolding the phases by
      their local density leads to universality of their local fluctuations for large
      M. A relation between the partial time delays and diagonal matrix elements of the
      Wigner-Smith matrix is revealed for ideal coupling. This helped us in deriving
      the joint probability distribution of partial time delays and the distribution of
      the Wigner time delay.

PMID- 11308698
TI  - Single-bubble sonoluminescence from noble gases.
AB  - Single-bubble sonoluminescence (SBSL) from noble gases in water is studied
      theoretically in order to clarify the reason of the distinguished feature that
      the luminescence is strong for all noble gases, while the other systems of
      cavitation luminescence are greatly enhanced by the presence of the heavy noble
      gas(xenon). It is clarified that in spite of the larger thermal conductivity of
      lighter noble gases the maximum temperature in a SBSL bubble of lighter noble
      gases is higher due both to the segregation of water vapor and noble gas inside a
      SBSL bubble and the stronger acoustic drive of a SBSL bubble of lighter noble
      gases.

PMID- 11308699
TI  - Shock wave criterion for propagating solitary states in driven surface waves.
AB  - Highly localized solitary states are observed to propagate along the surface of a
      thin two-dimensional fluid layer. The states are driven by means of a spatially
      uniform, temporally periodic, vertical acceleration (Faraday experiment) in a
      highly dissipative fluid. These states are shown to be formed by coupled fronts
      that propagate, periodically, as shock waves. A criterion for their formation
      based on shock initiation is presented. Both the characteristic form and
      interaction dynamics of the solitary states can be understood in this picture.

PMID- 11308700
TI  - Measuring nonextensitivity parameters in a turbulent Couette-Taylor flow.
AB  - We investigate probability density functions of velocity differences at different
      distances r measured in a Couette-Taylor flow for a range of Reynolds numbers Re.
      There is good agreement with the predictions of a theoretical model based on
      nonextensive statistical mechanics (where the entropies are nonadditive for
      independent subsystems). We extract the scale-dependent nonextensitivity
      parameter q(r,Re) from the laboratory data.

PMID- 11308701
TI  - Symmetry breaking, anomalous scaling, and large-scale flow generation in a
      convection cell.
AB  - We consider a convection process in thin loops of different geometries. At
      Ra=Ra(')(cr) a first transition leading to the generation of corner vortices is
      observed. At higher Ra (Ra>Ra(cr)) a coherent large-scale flow, which persists
      for a very long time, sets up. The mean velocity nu mass flux m, and the Nusselt
      number Nu in this flow scale with Ra as nu proportional to m proportional to
      Ra0.45 and Nu proportional to Ra0.9, respectively, in a wide range of r=(Ra
      Ra(cr))/Ra(cr) variation. The "normal" scaling nu proportional to sqrt[Ra] is
      detected as r-->0 and its range shrinks with decrease of the aspect ratio. The
      time evolution of the coherent flow is well described by the Landau amplitude
      equation with the appropriate selection of the Ra-dependent Landau constants.
      Analysis of the aspect ratio influence on the range of validity of anomalous
      scaling, observed in this paper, indicates the important role played by both
      thermal boundary conditions and geometry of the system.

PMID- 11308702
TI  - Equivalence of three approaches describing partially incoherent wave propagation
      in inertial nonlinear media.
AB  - We show that three approaches previously developed to describe partially
      incoherent wave propagation in inertial nonlinear media are in fact equivalent.
      This equivalence is formally established through the evolution of the mutual
      coherence function and by means of Karhunen-Loeve expansions.

PMID- 11308703
TI  - Critical properties of the reaction-diffusion model 2A-->3A, 2A-->0.
AB  - The steady-state phase diagram of the one-dimensional reaction-diffusion model 2A
      ->3A, 2A-->0 is studied through the non-Hermitian density matrix renormalization
      group. In the absence of single-particle diffusion the model reduces to the pair
      contact process, which has a phase transition in the universality class of
      directed percolation (DP) and an infinite number of absorbing steady states. When
      single-particle diffusion is added, the number of absorbing steady states is
      reduced to 2 and the model no longer shows DP critical behavior. The exponents
      theta=nu(parallel)/nu(perpendicular) and beta/nu(perpendicular) are calculated
      numerically. The value of beta/nu(perpendicular) is close to the value of the
      parity conserving universality class, in spite of the absence of local
      conservation laws.

PMID- 11308704
TI  - Pair contact process with diffusion: anew type of nonequilibrium critical
      behavior?
AB  - In the preceding article Carlon et al. investigate the critical behavior of the
      pair contact process with diffusion. Using density matrix renormalization group
      methods, they estimate the critical exponents, raising the possibility that the
      transition might belong to the same universality class as branching annihilating
      random walks with even numbers of offspring. This is surprising since the model
      does not have an explicit parity-conserving symmetry. In order to understand this
      contradiction, we estimate the critical exponents by Monte Carlo simulations. The
      results suggest that the transition might belong to a different universality
      class that has not been investigated before.

PMID- 11308705
TI  - Noisy random resistor networks: renormalized field theory for the multifractal
      moments of the current distribution.
AB  - We study the multifractal moments of the current distribution in randomly diluted
      resistor networks near the percolation threshold. When an external current is
      applied between two terminals x and x(') of the network, the lth multifractal
      moment scales as M((l))(I)(x,x(')) approximately equal /x-x'/(psi(l)/nu), where
      nu is the correlation length exponent of the isotropic percolation universality
      class. By applying our concept of master operators [Europhys. Lett. 51, 539
      (2000)] we calculate the family of multifractal exponents [psi(l)] for l>or=0 to
      two-loop order. We find that our result is in good agreement with numerical data
      for three dimensions.

PMID- 11308706
TI  - Variational mean-field study of a continuum model of crystalline tensionless
      surfaces.
AB  - We study analytically the equilibrium and near-equilibrium properties of a model
      of a d-dimensional surface relaxing via linear surface diffusion and subject to a
      lattice potential. We employ the variational mean-field formalism introduced by
      Saito for the study of the sine-Gordon model. In equilibrium, our variational
      theory predicts a first-order roughening transition between a flat low
      temperature phase and a rough high-temperature phase with the properties of the
      linear molecular-beam epitaxy equation. Moreover, the study of a Gaussian
      approximation to the Langevin dynamics of the system indicates that the surface
      shows hysteresis when temperature is continuously tuned. Out of equilibrium,
      these approximate Langevin dynamics show that the surface mobility can have
      different behaviors as a function of a driving flux. Some considerations are made
      regarding different underlying lattices, and connections are drawn to related
      models or different approaches to the same model we study.

PMID- 11308707
TI  - Mean first passage times of processes driven by white shot noise.
AB  - We consider mean first passage times in systems driven by white shot noise with
      exponentially distributed jump heights. Simple interpretable results are obtained
      and the linkage between those results and the steady-state probability density
      function of the process is presented. The virtual waiting-time or Takacs process
      (constant losses) and the shot noise process with linear losses are analyzed in
      depth, along with a more complex process with useful implications for the
      modeling of the soil moisture dynamics in hydrology.

PMID- 11308708
TI  - Partition function for a one-dimensional delta-function Bose gas.
AB  - The N-particle partition function of a one-dimensional delta-function Bose gas is
      calculated explicitly using only the periodic boundary condition (the Bethe
      ansatz equation). The N-particles cluster integrals are shown to be the same as
      those by the thermal Bethe ansatz method.

PMID- 11308709
TI  - Traveling waves in an optimal velocity model of freeway traffic.
AB  - Car-following models provide both a tool to describe traffic flow and algorithms
      for autonomous cruise control systems. Recently developed optimal velocity models
      contain a relaxation term that assigns a desirable speed to each headway and a
      response time over which drivers adjust to optimal velocity conditions. These
      models predict traffic breakdown phenomena analogous to real traffic
      instabilities. In order to deepen our understanding of these models, in this
      paper, we examine the transition from a linear stable stream of cars of one
      headway into a linear stable stream of a second headway. Numerical results of the
      governing equations identify a range of transition phenomena, including monotonic
      and oscillating travelling waves and a time- dependent dispersive adjustment
      wave. However, for certain conditions, we find that the adjustment takes the form
      of a nonlinear traveling wave from the upstream headway to a third, intermediate
      headway, followed by either another traveling wave or a dispersive wave further
      downstream matching the downstream headway. This intermediate value of the
      headway is selected such that the nonlinear traveling wave is the fastest stable
      traveling wave which is observed to develop in the numerical calculations. The
      development of these nonlinear waves, connecting linear stable flows of two
      different headways, is somewhat reminiscent of stop-start waves in congested flow
      on freeways. The different types of adjustments are classified in a phase diagram
      depending on the upstream and downstream headway and the response time of the
      model. The results have profound consequences for autonomous cruise control
      systems. For an autocade of both identical and different vehicles, the control
      system itself may trigger formations of nonlinear, steep wave transitions.
      Further information is available [Y. Sugiyama, Traffic and Granular Flow (World
      Scientific, Singapore, 1995), p. 137].

PMID- 11308710
TI  - Kinetic evolution of unmixing in an AlLi alloy using x-ray intensity fluctuation
      spectroscopy.
AB  - Irreversible decomposition of an AlLi single crystal has been studied by x-ray
      photon correlation spectroscopy. The precipitate coarsening follows a universal
      behavior, as measured by the time-resolved average scattering. Using coherent
      scattering, two-time correlation functions have been measured. The time evolution
      of the speckle pattern gives new insight into the process of unmixing; at least
      two regimes govern this evaporation-condensation coarsening process. One is
      related to the overall arrangement of precipitates, and the characteristic time
      is linear with annealing time. The other is related to the motion of interfaces
      and is related to Porod's law.

PMID- 11308711
TI  - Dynamic phase transition in a time-dependent Ginzburg-Landau model in an
      oscillating field.
AB  - The Ginzburg-Landau model below its critical temperature in a temporally
      oscillating external field is studied both theoretically and numerically. As the
      frequency or the amplitude of the external field is changed, a nonequilibrium
      phase transition is observed. This transition separates spatially uniform,
      symmetry-restoring oscillations from symmetry-breaking oscillations. Near the
      transition a perturbation theory is developed, and a switching phenomenon is
      found in the symmetry-broken phase. Our results confirm the equivalence of the
      present transition to that found in Monte Carlo simulations of kinetic Ising
      systems in oscillating fields, demonstrating that the nonequilibrium phase
      transition in both cases belongs to the universality class of the equilibrium
      Ising model in zero field. This conclusion is in agreement with symmetry
      arguments [G. Grinstein, C. Jayaprakash, and Y. He, Phys. Rev. Lett. 55, 2527
      (1985)] and recent numerical results [G. Korniss, C. J. White, P. A. Rikvold, and
      M. A. Novotny, Phys. Rev. E 63, 016120 (2001)]. Furthermore, a theoretical result
      for the structure function of the local magnetization with thermal noise, based
      on the Ornstein-Zernike approximation, agrees well with numerical results in one
      dimension.

PMID- 11308712
TI  - Noise properties in the Nagel-Schreckenberg traffic model.
AB  - The jamming transition in the stochastic traffic cellular automaton model of
      Nagel and Schreckenberg is examined. The behavior of the power spectrum is
      analyzed. Numerical results are presented. Satisfactory analytical approximations
      are established in both low frequency and high frequency regions. The intrinsic
      traffic states are revealed in the middle frequency range. A signature of 1/f
      noise is observed at the critical density of the transition.

PMID- 11308713
TI  - Self-organized criticality and universality in a nonconservative earthquake
      model.
AB  - We make an extensive numerical study of a two-dimensional nonconservative model
      proposed by Olami, Feder, and Christensen to describe earthquake behavior [Phys.
      Rev. Lett. 68, 1244 (1992)]. By analyzing the distribution of earthquake sizes
      using a multiscaling method, we find evidence that the model is critical, with no
      characteristic length scale other than the system size, in agreement with
      previous results. However, in contrast to previous claims, we find a convergence
      to universal behavior as the system size increases, over a range of values of the
      dissipation parameter alpha. We also find that both "free" and "open" boundary
      conditions tend to the same result. Our analysis indicates that, as L increases,
      the behavior slowly converges toward a power law distribution of earthquake sizes
      P(s) approximately equal s(-tau) with an exponent tau approximately equal 1.8.
      The universal value of tau we find numerically agrees quantitatively with the
      empirical value (tau=B+1) associated with the Gutenberg-Richter law.

PMID- 11308714
TI  - Domain wall formation in the Cahn-Hilliard-Cook equation.
AB  - Formation of domain walls during phase-separating transition in the Cahn-Hilliard
      Cook equation is studied. Density of domain wall scales like a sixth root of
      quench rate for equal concentrations and like a square root of quench rate for
      unequal concentrations of components. For a slow inhomogeneous transition, the
      density is linear in a velocity of temperature front.

PMID- 11308715
TI  - Exact sampling from nonattractive distributions using summary states.
AB  - Propp and Wilson's method of coupling from the past allows one to efficiently
      generate exact samples from attractive statistical distributions (e.g., the
      ferromagnetic Ising model). This method may be generalized to nonattractive
      distributions by the use of summary states, as first described by Huber. Using
      this method, we present exact samples from a frustrated antiferromagnetic
      triangular Ising model and the antiferromagnetic q=3 Potts model. We discuss the
      advantages and limitations of the method of summary states for practical
      sampling, paying particular attention to the slowing down of the algorithm at low
      temperature. In particular, we show that such slowing down can occur in the
      absence of a physical phase transition.

PMID- 11308716
TI  - Exact phase diagram of a model with aggregation and chipping.
AB  - We reexamine a simple lattice model of aggregation in which masses diffuse and
      coalesce upon contact with rate 1 and every nonzero mass chips off a single unit
      of mass and adds it to a randomly chosen neighbor with rate w. The dynamics
      conserves the average mass density rho and in the stationary state the system
      undergoes a nonequilibrium phase transition in the (rho-w) plane across a
      critical line rho(c)(w). In this paper, we show analytically that in arbitrary
      spatial dimensions rho(c)(w)=sqrt[w+1]-1 exactly and hence, remarkably, is
      independent of dimension. We also provide direct and indirect numerical evidence
      that strongly suggests that the mean field asymptotic results for the single site
      mass distribution function and the associated critical exponents are
      superuniversal, i.e., independent of dimension.

PMID- 11308717
TI  - Bunching transition in a time-headway model of a bus route.
AB  - A time-headway model is presented to mimic bus behavior on the bus route. The
      motion of a bus is described in terms of the time headway between its bus and the
      bus in front. We study the bunching behavior of buses induced by interacting with
      other buses and passengers. It is shown that the dynamical phase transitions
      among the inhomogeneous bunching phase, the homogeneous free phase, the
      coexisting phase, and the homogeneous congested phase occur with varying the
      initial time headway. We study the effect of not stopping at bus stops on the
      time-headway profile. It is found that the bunching transition lines are
      consistent with the neutral stability curves obtained by the linear stability
      analysis.

PMID- 11308718
TI  - Synergetic theory for a jamming transition in traffic flow.
AB  - The theory of a jamming transition is proposed for the homogeneous car-following
      model within the framework of the Lorenz scheme. We represent a jamming
      transition as a result of the spontaneous deviations of headway and velocity that
      is caused by the acceleration/braking rate to be higher than the critical value.
      The stationary values of headway and velocity deviations and time of
      acceleration/braking are derived as functions of control parameter (time needed
      for car to take the characteristic velocity).

PMID- 11308719
TI  - Phase-field modeling of stress-induced instabilities.
AB  - A phase-field approach describing the dynamics of a strained solid in contact
      with its melt is developed. Using a formulation that is independent of the state
      of reference chosen for the displacement field, we write down the elastic energy
      in an unambiguous fashion, thus obtaining an entire class of models. According to
      the choice of reference state, the particular model emerging from this class will
      become equivalent to one of the two independently constructed models on which
      brief accounts have been given recently [J. Muller and M. Grant, Phys. Rev. Lett.
      82, 1736 (1999); K. Kassner and C. Misbah, Europhys. Lett. 46, 217 (1999)]. We
      show that our phase-field approach recovers the sharp-interface limit
      corresponding to the continuum model equations describing the Asaro-Tiller
      Grinfeld instability. Moreover, we use our model to derive hitherto unknown sharp
      interface equations for a situation including a field of body forces. The
      numerical utility of the phase-field approach is demonstrated by reproducing some
      known results and by comparison with a sharp-interface simulation. We then
      proceed to investigate the dynamics of extended systems within the phase-field
      model which contains an inherent lower length cutoff, thus avoiding cusp
      singularities. It is found that a periodic array of grooves generically evolves
      into a superstructure which arises from a series of imperfect period doublings.
      For wave numbers close to the fastest-growing mode of the linear instability, the
      first period doubling can be obtained analytically. Both the dynamics of an
      initially periodic array and a random initial structure can be described as a
      coarsening process with winning grooves temporarily accelerating whereas losing
      ones decelerate and even reverse their direction of motion. In the absence of
      gravity, the end state of a laterally finite system is a single groove growing at
      constant velocity, as long as no secondary instabilities arise (that we have not
      been able to see with our code). With gravity, several grooves are possible, all
      of which are bound to stop eventually. A laterally infinite system approaches a
      scaling state in the absence of gravity and probably with gravity, too.

PMID- 11308720
TI  - Fate of zero-temperature Ising ferromagnets.
AB  - We investigate the relaxation of homogeneous Ising ferromagnets on finite
      lattices with zero-temperature spin-flip dynamics. On the square lattice, a
      frozen two-stripe state is apparently reached approximately 3/10 of the time,
      while the ground state is reached otherwise. The asymptotic relaxation is
      characterized by two distinct time scales with the longer stemming from the
      influence of a long-lived diagonal stripe defect. In greater than two dimensions,
      the probability to reach the ground state rapidly vanishes as the size increases
      and the system typically ends up wandering forever within an iso-energy set of
      stochastically "blinking" metastable states.

PMID- 11308721
TI  - Irreversible phase transitions driven by an oscillatory parameter in a far-from
      equilibrium system.
AB  - The dynamic response of a forest-fire model to the harmonic variation of an
      external parameter is studied by means of numerical simulations. Second-order
      irreversible phase transitions driven by the harmonic input are reported. The
      location of such transitions depends on both the amplitude and period of the
      input signal. By means of epidemic studies the relevant critical exponents can be
      determined, which allow us to place the reported transitions in the universality
      class of directed percolation. This conclusion is also supported by a field
      theoretical calculation.

PMID- 11308722
TI  - Elastic properties of inhomogeneous media with chaotic structure.
AB  - The elastic properties of an inhomogeneous medium with chaotic structure were
      derived within the framework of a fractal model using the iterative averaging
      approach. The predicted values of a critical index for the bulk elastic modulus
      and of the Poisson ratio in the vicinity of a percolation threshold were in fair
      agreement with the available experimental data for inhomogeneous composites.

PMID- 11308723
TI  - Soluble two-species diffusion-limited models in arbitrary dimensions.
AB  - A class of two-species (three-states) bimolecular diffusion-limited models of
      classical particles with hard-core reacting and diffusing in a hypercubic lattice
      of arbitrary dimension is investigated. The manifolds on which the equations of
      motion of the correlation functions close, are determined explicitly. This
      property allows to solve for the density and the two-point (two-time) correlation
      functions in arbitrary dimension for both, a translation invariant class and
      another one where translation invariance is broken. Systems with correlated as
      well as uncorrelated, yet random initial states can also be treated exactly by
      this approach. We discuss the asymptotic behavior of density and correlation
      functions in the various cases. The dynamics studied is very rich.

PMID- 11308724
TI  - Dynamic scaling for avalanches in disordered systems.
AB  - Dynamic scaling for fracture or breakdown process in disordered systems is
      investigated in a two-dimensional random field Ising model (RFIM). We find two
      evolving stages in the avalanche process in the RFIM. At the short-time regime, a
      power-law growth of the avalanche size Deltas is observed; and at late times, the
      conventional nucleation and growth process is found. At the critical point of the
      RFIM, the avalanche size is found to obey the dynamic scaling law Delta(s)
      approximately equal t((d-beta/nu)/z). From this dynamic scaling relation, the
      critical strength of the random field D(c) and the critical exponents, beta, nu,
      and z, are determined. The observed dynamics is explained by a simple nucleation
      theory of first-order phase transformations.

PMID- 11308725
TI  - Translational invariance in nucleation theories: theoretical formulation.
AB  - The consequences of spontaneously broken translational invariance on the
      nucleation-rate statistical prefactor in theories of first-order phase
      transitions are analyzed. A hybrid, semiphenomenological approach based on field
      theoretic analyses of condensation and modern density-functional theories of
      nucleation is adopted to provide a unified prescription for the incorporation of
      translational-invariance corrections to nucleation-rate predictions. A connection
      between these theories is obtained starting from a quantum-mechanical Hamiltonian
      and using methods developed in the context of studies on Bose-Einstein
      condensation. An extremum principle is used to derive an integro-differential
      equation for the spatially nonuniform mean-field order-parameter profile; the
      appropriate order parameter becomes the square root of the fluid density. The
      importance of the attractive intermolecular potential is emphasized, whereas the
      repulsive two-body potential is approximated by considering hard-sphere
      collisions. The functional form of the degenerate translational eigenmodes in
      three dimensions is related to the mean-field order parameter, and their
      contribution to the nucleation-rate prefactor is evaluated. The solution of the
      Euler-Lagrange variational equation is discussed in terms of either a proposed
      variational trial function or the complete numerical solution of the associated
      boundary-value integro-differential problem. Alternatively, if the attractive
      potential is not explicitly known, an approach that allows its formal
      determination from its moments is presented.

PMID- 11308726
TI  - Random field Ising systems on a general hierarchical lattice: rigorous
      inequalities.
AB  - Random Ising systems on a general hierarchical lattice with both random fields
      and random bonds are considered. Rigorous inequalities between eigenvalues of the
      Jacobian renormalization matrix at the pure fixed point are obtained. These
      inequalities lead to upper bounds on the crossover exponents [phi(i)].

PMID- 11308727
TI  - Renormalization group and perfect operators for stochastic differential
      equations.
AB  - We develop renormalization group (RG) methods for solving partial and stochastic
      differential equations on coarse meshes. RG transformations are used to calculate
      the precise effect of small-scale dynamics on the dynamics at the mesh size. The
      fixed point of these transformations yields a perfect operator: an exact
      representation of physical observables on the mesh scale with minimal lattice
      artifacts. We apply the formalism to simple nonlinear models of critical
      dynamics, and show how the method leads to an improvement in the computational
      performance of Monte Carlo methods.

PMID- 11308728
TI  - Intermittence and roughening of periodic elastic media.
AB  - We analyze intermittence and roughening of an elastic interface or domain wall
      pinned in a periodic potential, in the presence of random-bond disorder in 1+1
      and 2+1 dimensions. Though the ensemble average behavior is smooth, the typical
      behavior of a large sample is intermittent, and does not self-average to a smooth
      behavior. Instead, large fluctuations occur in the mean location of the interface
      and the onset of interface roughening is via an extensive fluctuation which leads
      to a jump in the roughness of order lambda, the period of the potential.
      Analytical arguments based on extreme statistics are given for the number of the
      minima of the periodicity visited by the interface and for the roughening
      crossover, which is confirmed by extensive exact ground state calculations.

PMID- 11308729
TI  - Decoherence and thermalization in a simple bosonic system.
AB  - Properties of a parameter-dependent quantum system with the Hamiltonian H(lambda)
      randomized by fluctuations of the parameter lambda in a narrow range are
      investigated. The model employed (the interacting boson model-1) exhibits a
      crossover behavior at a critical parameter value. Due to the fluctuations,
      individual eigenstates /psi(alpha)(lambda)> of the Hamiltonian become statistical
      ensembles of states [density matrices rho(alpha)(lambda)], which allows us to
      study effects related to the decoherence and thermalization. In the decoherence
      part, we evaluate von Neumann and information entropies of the density matrices
      rho(alpha)(lambda) and the overlaps of the eigenstates of the density matrix with
      various physically relevant bases. An increased decoherence at the " phase
      transitional" point and an exceptional role of the dynamic-symmetry U(5) basis
      are discovered. In the part devoted to the thermalization, we develop a method of
      how a given density matrix rho(alpha)(lambda) can be represented by an equivalent
      canonical (thermal) ensemble. Thermodynamic consequences of the quantum "phase
      transition" (related, in particular, to the specific heat of the thermal
      equivalent) are discussed.

PMID- 11308730
TI  - Self-generated power-law tails in probability distributions.
AB  - We consider random processes characterized by the presence of correlations in
      their variance, or more generally in some of their moments. Typical examples are
      constituted by autoregressive conditional heteroskedasticity (ARCH) processes
      which are known to display power-law tails in the associated probability
      distributions. Here, we determine the corresponding exponents exactly and extend
      these results to relaxation phenomena which can be expected to play a role in
      natural sciences.

PMID- 11308731
TI  - Locked-to-running transition in the two-dimensional underdamped driven Frenkel
      Kontorova model.
AB  - We study the nonlinear dc response of a two-dimensional underdamped system of
      interacting atoms subject to an isotropic periodic external potential with
      triangular symmetry. We consider various values of the effective elastic constant
      of the system, two different atomic interaction potentials, and different
      concentrations of atoms. In the case of a closely packed layer, when its
      structure is commensurate with the substrate, there is a locked-to-running
      transition as a function of the driving force, whose mechanism depends on the
      effective elastic constant. For a low elastic constant, where the layer is weakly
      coupled, the transition is achieved via the creation of an avalanche of moving
      particles that leaves a depleted region in its wake. On increasing the effective
      elastic constant the depleted region becomes less marked and there is a crossover
      to a scenario in which an island of moving particles nucleates the transition. In
      the case of a partially filled atomic layer, several dynamical phase transitions
      between states with different atomic mobility are observed. The mobility of atoms
      as a function of the external force can vary nonmonotonically with increasing
      force. For the case of a small external damping, the system can be trapped at a
      large force in an immobile metastable state, thus demonstrating a "fuse-safety
      device" on an atomic scale.

PMID- 11308732
TI  - Self-organized criticality and the self-organizing map.
AB  - The self-organizing map (SOM), a biologically inspired, learning algorithm from
      the field of artificial neural networks, is presented as a self-organized
      critical (SOC) model of the extremal dynamics family. The SOM's ability to
      converge to an ordered configuration, independent of the initial state, is known
      and has been demonstrated, in the one-dimensional case. In this ordered
      configuration it is now indicated by analysis and shown by simulation that the
      dynamics of the SOM are critical. By viewing the SOM as a SOC system, alternative
      interpretations of learning, the organized configuration, and the formation of
      topographic maps can be made.

PMID- 11308733
TI  - Random walks on fractals and stretched exponential relaxation.
AB  - Stretched exponential relaxation [exp-(t/tau)(beta(K))] is observed in a large
      variety of systems but has not been explained so far. Studying random walks on
      percolation clusters in curved spaces whose dimensions range from 2 to 7, we show
      that the relaxation is accurately a stretched exponential and is directly
      connected to the fractal nature of these clusters. Thus we find that in each
      dimension the decay exponent beta(K) is related to well-known exponents of the
      percolation theory in the corresponding flat space. We suggest that the stretched
      exponential behavior observed in many complex systems (polymers, colloids,
      glasses...) is due to the fractal character of their configuration space.

PMID- 11308734
TI  - Heat kernel regularization of the effective action for stochastic reaction
      diffusion equations.
AB  - The presence of fluctuations and nonlinear interactions can lead to scale
      dependence in the parameters appearing in stochastic differential equations.
      Stochastic dynamics can be formulated in terms of functional integrals. In this
      paper we apply the heat kernel method to study the short distance
      renormalizability of a stochastic (polynomial) reaction-diffusion equation with
      real additive noise. We calculate the one-loop effective action and its
      ultraviolet scale dependent divergences. We show that for white noise a
      polynomial reaction-diffusion equation is one-loop finite in d=0 and d=1, and is
      one-loop renormalizable in d=2 and d=3 space dimensions. We obtain the one-loop
      renormalization group equations and find they run with scale only in d=2.

PMID- 11308735
TI  - Transcritical riddling in a system of coupled maps.
AB  - The transition from fully synchronized behavior to two-cluster dynamics is
      investigated for a system of N globally coupled chaotic oscillators by means of a
      model of two coupled logistic maps. An uneven distribution of oscillators between
      the two clusters causes an asymmetry to arise in the coupling of the model
      system. While the transverse period-doubling bifurcation remains essentially
      unaffected by this asymmetry, the transverse pitchfork bifurcation is turned into
      a saddle-node bifurcation followed by a transcritical riddling bifurcation in
      which a periodic orbit embedded in the synchronized chaotic state loses its
      transverse stability. We show that the transcritical riddling transition is
      always hard. For this, we study the sequence of bifurcations that the
      asynchronous point cycles produced in the saddle-node bifurcation undergo, and
      show how the manifolds of these cycles control the magnitude of asynchronous
      bursts. In the case where the system involves two subpopulations of oscillators
      with a small mismatch of the parameters, the transcritical riddling will be
      replaced by two subsequent saddle-node bifurcations, or the saddle cycle involved
      in the transverse destabilization of the synchronized chaotic state may smoothly
      shift away from the synchronization manifold. In this way, the transcritical
      riddling bifurcation is substituted by a symmetry-breaking bifurcation, which is
      accompanied by the destruction of a thin invariant region around the symmetrical
      chaotic state.

PMID- 11308736
TI  - Integrals of motion and semipermeable surfaces to bound the amplitude of a plasma
      instability.
AB  - We study a dissipative dynamical system that models a parametric instability in a
      plasma. This instability is due to the interaction of a whistler with the ion
      acoustic wave and a plasma oscillation near the lower hybrid resonance. The
      amplitude of these three oscillations obey a three-dimensional system of ordinary
      differential equations which exhibits chaos for certain parameter values. By
      using certain "integrability informations" we have on the system, we get
      geometrical bounds for its chaotic attractor, leading to an upper bound for its
      Lyapunov dimension. On the other hand, we also obtain ranges of values of the
      system's parameters for which there is no chaotic motion.

PMID- 11308737
TI  - Parametric dependent Hamiltonians, wave functions, random matrix theory, and
      quantal-classical correspondence.
AB  - We study a classically chaotic system that is described by a Hamiltonian
      H(Q,P;x), where (Q,P) are the canonical coordinates of a particle in a two
      dimensional well, and x is a parameter. By changing x we can deform the "shape"
      of the well. The quantum eigenstates of the system are /n(x)>. We analyze
      numerically how the parametric kernel P(n/m)=/<n(x)/m(x(0))>/(2) evolves as a
      function of delta(x)[triple bond](x-x(0)). This kernel, regarded as a function of
      n-m, characterizes the shape of the wave functions, and it also can be
      interpreted as the local density of states. The kernel P(n/m) has a well-defined
      classical limit, and the study addresses the issue of quantum-classical
      correspondence. Both the perturbative and the nonperturbative regimes are
      explored. The limitations of the random matrix theory approach are demonstrated.

PMID- 11308738
TI  - Synchronization of Kauffman networks.
AB  - We analyze the synchronization transition for a pair of coupled identical
      Kauffman networks in the chaotic phase. The annealed model for Kauffman networks
      shows that synchronization appears through a transcritical bifurcation and
      provides an approximate description for the whole dynamics of the coupled
      networks. We show that these analytical predictions are in good agreement with
      numerical results for sufficiently large networks and study finite-size effects
      in detail. Preliminary analytical and numerical results for partially disordered
      networks are also presented.

PMID- 11308739
TI  - Chaotic dynamics from interspike intervals.
AB  - Considering two different mathematical models describing chaotic spiking
      phenomena, namely, an integrate-and-fire and a threshold-crossing model, we
      discuss the problem of extracting dynamics from interspike intervals (ISIs) and
      show that the possibilities of computing the largest Lyapunov exponent (LE) from
      point processes differ between the two models. We also consider the problem of
      estimating the second LE and the possibility to diagnose hyperchaotic behavior by
      processing spike trains. Since the second exponent is quite sensitive to the
      structure of the ISI series, we investigate the problem of its computation.

PMID- 11308740
TI  - Singular statistics.
AB  - We consider the statistical distribution of zeros of random meromorphic functions
      whose poles are independent random variables. It is demonstrated that correlation
      functions of these zeros can be computed analytically, and explicit calculations
      are performed for the two-point correlation function. This problem naturally
      appears in, e.g., rank-1 perturbation of an integrable Hamiltonian and, in
      particular, when a delta-function potential is added to an integrable billiard.

PMID- 11308741
TI  - Dynamic localization of Lyapunov vectors in Hamiltonian lattices.
AB  - The convergence of the Lyapunov vector toward its asymptotic shape is
      investigated in two different one-dimensional Hamiltonian lattices: the so-called
      Fermi-Pasta-Ulam and Phi(4) chains. In both cases, we find an anomalous behavior,
      i.e., a clear difference from the previously conjectured analogy with the Kardar
      Parisi-Zhang equation. The origin of the discrepancy is eventually traced back to
      the existence of nontrivial long-range correlations both in space and time. As a
      consequence of this anomaly, we find that, in a Hamiltonian lattice, the largest
      Lyapunov exponent is affected by stronger finite-size corrections than standard
      space-time chaos.

PMID- 11308742
TI  - Milnor strange nonchaotic attractor with complex basin of attraction.
AB  - The transcritical blowout bifurcation of a quasiperiodic torus on an invariant
      subspace is studied in this paper. We found that the strange nonchaotic attractor
      (SNA) beyond the blowout bifurcation is only a weak attractor in the sense of
      Milnor. This is different from the popularly studied case where the Milnor
      attractor is a chaotic one with a riddled basin of attraction. Characters of this
      Milnor SNA and the influence of a random noise are studied.

PMID- 11308743
TI  - Nonlinear noise reduction using reference data.
AB  - We introduce a method to clean uncorrelated deterministic and stochastic noise
      components from time series. It combines recently developed techniques for
      nonlinear projection with properties of the wavelet transform to extract noise in
      state space. The method requires that time series are generated by a dynamical
      system which is at least approximately deterministic and that they are recorded
      together with a reference signal. Its efficiency was tested on both simulated
      signals and measured magnetic fields of the heart. Convincing results are
      obtained even at low signal-to-noise ratios.

PMID- 11308744
TI  - Strong desynchronizing effects of weak noise in globally coupled systems.
AB  - In assemblies of globally coupled dynamical units, weak noise perturbing
      independently the individual units can cause anomalous dispersion in the
      synchronized cloud of the units in the phase space. When the noise-free dynamics
      of the synchronized assembly is nonperiodic, various moments of the linear
      dimension of the cloud as a function of the noise strength exhibit multiscaling
      properties with parameter-dependent scaling exponents. Some numerical evidence of
      this peculiar behavior as well as its interpretation in terms of a multiplicative
      stochastic process with small additive noise is provided. Universality of the
      phenomenon is also discussed.

PMID- 11308745
TI  - Interacting pairs of periodic solutions lead to tori in lasers subject to delayed
      feedback.
AB  - Models of class-B lasers subject to either an optoelectronic or an optical
      feedback are investigated analytically and numerically. We derive slow time
      amplitude equations from the laser delay differential equations and find multiple
      bifurcating and isolated branches of periodic solutions. We then show that
      secondary bifurcations to tori result from the interaction of pairs of Hopf
      bifurcations. The branches emerging from these bifurcations are followed
      numerically using a continuation method developed for delay differential
      equations.

PMID- 11308746
TI  - Using thresholding at varying intervals to obtain different temporal patterns.
AB  - We show how stroboscopic threshold mechanisms can be effectively employed to
      obtain a wide range of stable cyclic behavior from chaotic systems, by simply
      varying the frequency of control. We demonstrate the success of the scheme in a
      prototypical one-dimensional map, as well as in a three-dimensional system
      modeling lasers where the threshold action is implemented on any one of the
      variables. It is evident that thresholding is capable of yielding exact limit
      cycles of varying periods and geometries when implemented at different intervals
      (even when very infrequent). This suggests a simple and potent mechanism for
      selecting different regular temporal patterns from chaotic dynamics.

PMID- 11308747
TI  - Lyapunov exponents in disordered chaotic systems: avoided crossing and level
      statistics.
AB  - The behavior of the Lyapunov exponents (LEs) of a disordered system consisting of
      mutually coupled chaotic maps with different parameters is studied. The LEs are
      demonstrated to exhibit avoided crossing and level repulsion, qualitatively
      similar to the behavior of energy levels in quantum chaos. Recent results for the
      coupling dependence of the LEs of two coupled chaotic systems are used to explain
      the phenomenon and to derive an approximate expression for the distribution
      functions of LE spacings. The depletion of the level spacing distribution is
      shown to be exponentially strong at small values. The results are interpreted in
      terms of the random matrix theory.

PMID- 11308748
TI  - Phase signal coupling induced n:m phase synchronization in drive-response
      oscillators.
AB  - We have studied phase synchronization between two identical Rossler oscillators
      connected in the drive-response configuration by a single phase signal. Before
      the transition to phase synchronization, the distribution of the time interval
      between consecutive 2pi jumps shows several sharp peaks. With a strong phase
      signal coupling, the n:m phase synchronization between the oscillators can be
      achieved. For the n (not equal) m phase synchronizing state, some values of
      coupling strength result in a phenomenon characterized by a reduction in the mean
      amplitude of the response termed amplitude reduction. In these regions, the mean
      rotation speed of the response remains approximately constant while the locking
      ratio n:m varies.

PMID- 11308749
TI  - Approach to energy eigenvalues and eigenfunctions from nonperturbative regions of
      eigenfunctions.
AB  - We study the approach to energy eigenvalues and eigenfunctions of Hamiltonian
      matrices with band structure from diagonalization of their truncated matrices.
      Making use of a generalization of Brillouin-Wigner perturbation theory, it is
      shown that in order to obtain approximate energy eigenvalues and eigenfunctions
      the sizes of truncated matrices should be larger than the nonperturbative regions
      of the eigenfunctions by several band width of the Hamiltonian matrix, with the
      nonperturbative regions being able to be estimated before the eigenfunctions are
      known. This prediction is checked numerically by the Wigner-band random-matrix
      model, which shows that 99% of eigenfunctions can be obtained when the sizes of
      truncated matrices are larger than those of the nonperturbative regions of the
      eigenfunctions by three band widths of the Hamiltonian matrix, on average.

PMID- 11308750
TI  - Cluster synchronization modes in an ensemble of coupled chaotic oscillators.
AB  - Considering systems of diffusively coupled identical chaotic oscillators, an
      effective method to determine the possible states of cluster synchronization and
      ensure their stability is presented. The method, which may find applications in
      communication engineering and other fields of science and technology, is
      illustrated through concrete examples of coupled biological cell models.

PMID- 11308751
TI  - Learning to control a complex multistable system.
AB  - In this paper the control of a periodically kicked mechanical rotor without
      gravity in the presence of noise is investigated. In recent work it was
      demonstrated that this system possesses many competing attracting states and thus
      shows the characteristics of a complex multistable system. We demonstrate that it
      is possible to stabilize the system at a desired attracting state even in the
      presence of high noise level. The control method is based on a recently developed
      algorithm [S. Gadaleta and G. Dangelmayr, Chaos 9, 775 (1999)] for the control of
      chaotic systems and applies reinforcement learning to find a global optimal
      control policy directing the system from any initial state towards the desired
      state in a minimum number of iterations. Being data-based, the method does not
      require any information about governing dynamical equations.

PMID- 11308752
TI  - Sensitive boundary condition dependence of noise-sustained structure.
AB  - Sensitive boundary condition dependence (BCD) is reported in a convectively
      unstable system with noise, where the amplitude of generated oscillatory dynamics
      in the downstream depends sensitively on the boundary value. This BCD is
      explained in terms of the decrease (relaxation) of the comoving Lyapunov exponent
      (characterizing the convective instability) from upstream to downstream [K.
      Fujimoto and K. Kaneko, Physica D 129, 203 (1999)]. It is shown that a fractal
      BCD appears if the dynamics that represent the spatial change of the fixed point
      includes transient chaotic dynamics, and if appropriate intensity of noise is
      presented. By considering as an example a one-way-coupled map lattice, this
      theory for BCD is demonstrated.

PMID- 11308753
TI  - Analysis of a parametrically driven pendulum.
AB  - We study in this paper the behavior of a periodically driven nonlinear mechanical
      system. Bifurcation diagrams are found which locate regions of quasiperiodic,
      periodic, and chaotic behavior within the parameter space of the system. We also
      conduct a symbolic analysis of the model which demonstrates that the symbolic
      dynamics of two-dimensional maps can be applied effectively to the study of
      ordinary differential equations in order to gain global knowledge about them.

PMID- 11308754
TI  - Real-time memory on an excitable field.
AB  - Recently, we proposed a novel method for computing logic operations based on the
      time-sequential information in a geometrically arranged excitable field. As an
      extension of this study, in the present article we describe a strategy for
      creating real-time memory. Using a numerical simulation, we show that input pulse
      trains can be stored as a sequence of rotating traveling waves in a circular
      excitable field, by using its characteristics as a diode due to spatially
      asymmetric arrangement. Furthermore, through an experiment on an excitable
      chemical reaction, we demonstrate that this real-time memory actually works in
      the real world.

PMID- 11308755
TI  - Dimension of interaction dynamics.
AB  - A method allowing one to distinguish interacting from noninteracting systems
      based on available time series is proposed and investigated. Some facts
      concerning generalized Renyi dimensions that form the basis of our method are
      proved. We show that one can find the dimension of the part of the attractor of
      the system connected with interaction between its parts. We use our method to
      distinguish interacting from noninteracting systems on the examples of logistic
      and Henon maps. A classification of all possible interaction schemes is given.

PMID- 11308756
TI  - Localization transition in incommensurate non-Hermitian systems.
AB  - A class of one-dimensional lattice models with an incommensurate complex
      potential V(theta)=2[lambda(r) cos(theta)+i(lambda)(i) sin(theta)] is found to
      exhibit a localization transition at /lambda(r)/+/lambda(i)/=1. This transition
      from extended to localized states manifests itself in the behavior of the complex
      eigenspectum. In the extended phase, states with real eigenenergies have a finite
      measure, and this measure goes to zero in the localized phase. Furthermore, all
      extended states exhibit real spectra provided /lambda(r)/>or=/lambda(i)/. Another
      interesting feature of the system is the fact that the imaginary part of the
      spectrum is sensitive to the boundary conditions only at the onset to
      localization.

PMID- 11308757
TI  - Bicritical scaling behavior in unidirectionally coupled oscillators.
AB  - We study the scaling behavior of period doublings in a system of two
      unidirectionally coupled parametrically forced pendulums near a bicritical point
      where two critical lines of period-doubling transition to chaos in both
      subsystems meet. When crossing a bicritical point, a hyperchaotic attractor with
      two positive Lyapunov exponents appears, i.e., a transition to hyperchaos occurs.
      Varying the control parameters of the two subsystems, the unidirectionally
      coupled parametrically forced pendulums exhibit multiple period-doubling
      transitions to hyperchaos. For each transition to hyperchaos, using both a
      "residue-matching" renormalization group method and a direct numerical method, we
      make an analysis of the bicritical scaling behavior. It is thus found that the
      second response subsystem exhibits a new type of non-Feigenbaum scaling behavior,
      while the first drive subsystem is in the usual Feigenbaum critical state. The
      universality of the bicriticality is also examined for several different types of
      unidirectional couplings.

PMID- 11308758
TI  - Chaotic advection near a three-vortex collapse.
AB  - Dynamical and statistical properties of tracer advection are studied in a family
      of flows produced by three point-vortices of different signs. Tracer dynamics is
      analyzed by numerical construction of Poincare sections, and is found to be
      strongly chaotic: advection pattern in the region around the center of vorticity
      is dominated by a well developed stochastic sea, which grows as the vortex
      system's initial conditions are set closer to those leading to the collapse of
      the vortices; at the same time, the islands of regular motion around vortices,
      known as vortex cores, shrink. An estimation of the core's radii from the minimum
      distance of vortex approach to each other is obtained. Tracer transport was found
      to be anomalous: for all of the three numerically investigated cases, the
      variance of the tracer distribution grows faster than a linear function of time,
      corresponding to a superdiffusive regime. The transport exponent varies with time
      decades, implying the presence of multi-fractal transport features. Yet, its
      value is never too far from 3/2, indicating some kind of universality. Statistics
      of Poincare recurrences is non-Poissonian: distributions have long power-law
      tails. The anomalous properties of tracer statistics are the result of the
      complex structure of the advection phase space, in particular, of strong
      stickiness on the boundaries between the regions of chaotic and regular motion.
      The role of the different phase space structures involved in this phenomenon is
      analyzed. Based on this analysis, a kinetic description is constructed, which
      takes into account different time and space scalings by using a fractional
      equation.

PMID- 11308759
TI  - Phase-frequency synchronization in a chain of periodic oscillators in the
      presence of noise and harmonic forcings.
AB  - We study numerically the effects of noise and periodic forcings on cluster
      synchronization in a chain of Van der Pol oscillators. We generalize the notion
      of effective synchronization to the case of a spatially extended system. It is
      shown that the structure of synchronized clusters can be effectively controlled
      by applying local external forcings. The effect of amplitude relations on the
      phase dynamics is also explored.

PMID- 11308760
TI  - Transition to stochastic synchronization in spatially extended systems.
AB  - Spatially extended dynamical systems, namely coupled map lattices, driven by
      additive spatio-temporal noise are shown to exhibit stochastic synchronization.
      In analogy with low-dimensional systems, synchronization can be achieved only if
      the maximum Lyapunov exponent becomes negative for sufficiently large noise
      amplitude. Moreover, noise can suppress also the nonlinear mechanism of
      information propagation, which may be present in the spatially extended system.
      An example of phase transition is observed when both the linear and the nonlinear
      mechanisms of information production disappear at the same critical value of the
      noise amplitude. The corresponding critical properties cannot be estimated
      numerically with great accuracy, but some general argument suggests that they
      could be ascribed to the Kardar-Parisi-Zhang universality class. Conversely, when
      the nonlinear mechanism prevails on the linear one, another type of phase
      transition to stochastic synchronization occurs. This one is shown to belong to
      the universality class of directed percolation.

PMID- 11308761
TI  - Fractals and dynamical chaos in a two-dimensional Lorentz gas with sinks.
AB  - We consider a two-dimensional periodic reactive Lorentz gas, in which a moving
      point particle undergoes elastic collisions on fixed hard disks and annihilates
      on absorbing disks, called sinks. We present clear evidence of the existence of a
      fractal repeller in this open system. Moreover, we establish a relation between
      the reaction rate, describing the macroscopic evolution of the system, and two
      characteristic quantities of the microscopic chaos: the average Lyapunov exponent
      and the Hausdorff codimension of the fractal repeller.

PMID- 11308762
TI  - Singularities in the Boussinesq equation and in the generalized Korteweg-de Vries
      equation.
AB  - In this paper, two kinds of analytic singular solutions (finite-time and infinite
      time singular solutions) of two classical wave equations (the Boussinesq equation
      and a generalized Korteweg-de Vries equation) are obtained by means of the
      improved homogeneous balance method and a nonlinear transformation. The solutions
      show that special singular wave patterns exist in the classical models of shallow
      water wave problem.

PMID- 11308763
TI  - Anomalous scaling in two models of passive scalar advection: effects of
      anisotropy and compressibility.
AB  - The problem of the effects of compressibility and large-scale anisotropy on
      anomalous scaling behavior is considered for two models describing passive
      advection of scalar density and tracer fields. The advecting velocity field is
      Gaussian, delta correlated in time, and scales with a positive exponent epsilon.
      Explicit inertial-range expressions for the scalar correlation functions are
      obtained; they are represented by superpositions of power laws with nonuniversal
      amplitudes and universal anomalous exponents (dependent only on epsilon and
      alpha, the compressibility parameter). The complete set of anomalous exponents
      for the pair correlation functions is found nonperturbatively, in any space
      dimension d, using the zero-mode technique. For higher-order correlation
      functions, the anomalous exponents are calculated to O(epsilon(2)) using the
      renormalization group. As in the incompressible case, the exponents exhibit a
      hierarchy related to the degree of anisotropy: the leading contributions to the
      even correlation functions are given by the exponents from the isotropic shell,
      in agreement with the idea of restored small-scale isotropy. As the degree of
      compressibility increases, the corrections become closer to the leading terms.
      The small-scale anisotropy reveals itself in the odd ratios of correlation
      functions: the skewness factor slowly decreases going down to small scales for
      the incompressible case, but starts to increase if alpha is large enough. The
      higher odd dimensionless ratios (hyperskewness, etc.) increase, thus signaling
      persistent small-scale anisotropy; this effect becomes more pronounced for larger
      values of alpha.

PMID- 11308764
TI  - Stability of a viscous fluid in an oscillating gravitational field.
AB  - The stability of the interface of a viscous incompressible fluid superimposed on
      a massless fluid is studied for the case of an oscillating gravitational field.
      For the viscous case, the dispersion relation is shown to represent an infinite
      determinant of the Hill type, which is investigated analytically. The method
      presented allows one to find the whole dispersion curve of the instability and
      its asymptotics in an explicit form. The stabilizing effect of the externally
      imposed oscillations leads to the appearance of stability windows on the growth
      rate spectrum. Illustrations are given for the influence of all the parameters of
      the problem on this effect.

PMID- 11308765
TI  - Cascades in helical turbulence.
AB  - We suggest the existence of a characteristic inner scale xi for helicity
      dissipation in a regime of hydrodynamic fully developed turbulence and estimate
      it on dimensional grounds. This scale is always larger than the Kolmogorov scale
      eta and their ratio eta/xi vanishes in the high Reynolds number limit, so the
      flow will always be helicity free in the small scales. These ideas are
      illustrated in a shell model of turbulence.

PMID- 11308766
TI  - Amplitude measurements of Faraday waves.
AB  - A light reflection technique is used to measure quantitatively the surface
      elevation of Faraday waves. The performed measurements cover a wide parameter
      range of driving frequencies and sample viscosities. In the capillary wave regime
      the bifurcation diagrams exhibit a frequency independent scaling proportional to
      the wavelength. We also provide numerical simulations of the full Navier-Stokes
      equations, which are in quantitative agreement up to supercritical drive
      amplitudes of epsilon approximately equal 20%. The validity of an existing
      perturbation analysis is found to be limited to epsilon<2.5%.

PMID- 11308767
TI  - Formulation of subgrid stresses for large-scale fluid equations.
AB  - A formulation is presented based on a previously derived self-consistent
      procedure for obtaining subgrid scale models for complex system of equations.
      Using linear stability analysis and numerical simulations of the one-dimensional
      Burgers equation the formulation is shown to be very stable numerically and to
      reproduce accurately the large-scale flow of a high-resolution, direct
      simulation. Moreover, the resulting equation has a structure very similar to the
      viscous Camassa-Holm equation recently introduced in the modeling of turbulent
      flows.

PMID- 11308768
TI  - Saffman-Taylor problem on a sphere.
AB  - The Saffman-Taylor problem addresses the morphological instability of an
      interface separating two immiscible, viscous fluids when they move in a narrow
      gap between two flat parallel plates (Hele-Shaw cell). In this work, we extend
      the classic Saffman-Taylor situation, by considering the flow between two curved,
      closely spaced, concentric spheres (spherical Hele-Shaw cell). We derive the mode
      coupling differential equation for the interface perturbation amplitudes and
      study both linear and nonlinear flow regimes. The effect of the spherical cell
      (positive) spatial curvature on the shape of the interfacial patterns is
      investigated. We show that stability properties of the fluid-fluid interface are
      sensitive to the curvature of the surface. In particular, it is found that
      positive spatial curvature inhibits finger tip-splitting. Hele-Shaw flow on
      weakly negative, curved surfaces is briefly discussed.

PMID- 11308769
TI  - Transitions of macroscopic structures and self-induced chaos observed in plasmas
      by a dc hollow cathode discharge having features of nonlinear open systems.
AB  - A novel experimental investigation is presented on the connection between
      discontinuous transitions of macroscopic structures of plasma and self-induced
      chaotic oscillations characterized by the positive Lyapunov exponents lambda(L)
      through the period-doubling route in a dc hollow cathode discharge, which has
      features of nonlinear open systems. We have clarified experimentally that there
      appear different discharge modes accompanying the discontinuous transitions, and
      detailed qualitative explanations are presented about the mechanism of those
      transitions. It is shown that fundamental frequencies of the self-induced
      periodic oscillations with nonpositive lambda(L) change with the changes of
      discharge current, and the amplitude of chaotic oscillations with the positive
      lambda(L) jumps up almost one order higher than that of nonchaotic ones with the
      nonpositive lambda(L). The self-induced chaotic oscillations with the positive
      lambda(L) have been observed near two edges of discontinuous transitions of
      plasma structures, suggesting that the chaotic mode is associated with the
      discontinuous transition of macroscopic structures in some nonlinear open
      systems.

PMID- 11308770
TI  - Ionizational instability in an ionized inert gas flowing in a magnetic field.
AB  - We discuss the evolution of ionization instability, which gives rise to the
      formation of regular structures in plasma. The experiment was conducted in a disk
      magnetohydrodynamic channel in Xe. The evolution of luminous inhomogeneities, and
      changes in the luminosities of individual inhomogeneities, are traced. Electron
      concentrations and temperatures in fluctuations are measured. Average values of
      the electron concentration and temperature, plasma conductivity, and the Hall
      parameter are estimated. The average conductivity and Hall parameter are compared
      with the effective values. The influence of positive and negative fluctuations in
      plasma parameters on the enhancement of ionization oscillations and average
      current is analyzed. Based on experimental data, a mechanism is suggested that is
      responsible for the increase in the effective conductivity of ionizationally
      unstable inert gas plasma with increasing magnetic induction.

PMID- 11308771
TI  - Experimental study of a subpicosecond pulse laser interacting with metallic and
      dielectric targets.
AB  - We have studied laser absorption, hot electron emission, and the energy spectrum
      of hot electrons produced during the interaction of a 150 fs, 5 mJ, 800 nm p
      polarized laser pulse at 8x10(15) W/cm(2) with metallic and dielectric target
      materials. Because dielectric targets are much less conductive, the charge
      separation potential in dielectric targets is higher than that of metallic
      targets. This leads to a smaller laser absorption, fewer emitted electrons, and a
      lower hot electron temperature in dielectric than in metallic targets.

PMID- 11308772
TI  - Atomic spectral line free parameter deconvolution procedure.
AB  - We report an advanced numerical procedure for deconvolution of theoretical
      asymmetric convolution integral of a Gaussian and a plasma broadened spectral
      line profile j(A,R)(lambda) for spectal lines. Our method determines all
      broadening parameters, self-consistently and directly from the line profile with
      minimal assumptions or prior knowledge. This method is useful for obtaining
      complete information on all plasma parameters directly from the recorded shape of
      a single line, which is very important in case no other diagnostic methods are
      available. The method is also convenient for determination of plasma parameters
      in the case of a symmetrical profile such as Voigt one.

PMID- 11308773
TI  - Stochastic properties of strongly coupled plasmas.
AB  - Stochastic properties of equilibrium strongly coupled plasmas are investigated by
      a molecular dynamics method. The Krylov-Kolmogorov entropy K and the dynamical
      memory time t(m) are calculated both for electrons and ions with mass ratios 10
      10(5). Two values of K entropy for ions are discovered corresponding to electron
      and ion time scales. The dependence of the K entropy on the number of particles,
      the nonideality parameter, and the form of the interaction potential is
      investigated. The problem of the accuracy of molecular dynamics simulations is
      discussed. A universal relation between Kt(m) and the fluctuation of the total
      energy of the system is obtained. The relation does not depend on the numerical
      integration scheme, temperature, density, and the interparticle interaction
      potential, so that it may be applied to arbitrary dynamic systems. Transition
      from dynamic to stochastic correlation is treated for both electron and ion
      velocity autocorrelation functions, for Langmuir and ion-sound plasma wave
      dynamic structure factors. We point to quantum uncertainty as a physical reason
      which limits dynamic (Newton) correlation for times greater than t(m).

PMID- 11308774
TI  - Levitation of cylindrical particles in the sheath of an rf plasma.
AB  - Microrods were levitated in the collisional sheath of a rf plasma. Rods below a
      critical length settle vertically, parallel to the electric field, while longer
      rods float horizontally. Usually rods with other inclinations spin about a
      vertical axis. These experimental features fit well with a model that includes a
      theoretical profile for the sheath, a plasma model for the screening length,
      which increases going deeper in the sheath, and a plasma theory for the charging
      of the rod's elements. Despite the agreement this paper highlights the need for a
      better understanding of the charging mechanism of bodies in sheaths and of the
      transition region in collisional sheaths.

PMID- 11308775
TI  - Necessity of bunch compression for heavy-ion-induced hydrodynamics and studies of
      beam fragmentation in solid targets at a proposed synchrotron facility.
AB  - This paper presents two-dimensional numerical simulations of hydrodynamic
      response of a solid lead cylindrical target that is irradiated by an intense
      uranium beam having a particle energy of 1 GeV/u and that consists of 10(12)
      particles. Different time profiles have been considered for the beam power that
      include a case where the beam consists of five identical parabolic bunches with
      equal separation between neighboring bunches as well as a beam that consists of a
      single bunch. For the single bunch case we consider two different values for
      pulse length, namely, 1000 and 50 ns, respectively. Moreover we allow for two
      different values for the beam radius that is 0.5 and 1.0 mm, respectively. These
      calculations show that in order to achieve a high degree of beam-target coupling,
      it is absolutely essential to use a single bunched beam that has a reasonably
      short pulse length, which is 50 ns in this case. Such a large beam-target
      coupling efficiency is highly desirable for creating high-density strongly
      coupled plasmas as well as for studies that involve fragmentation of the
      projectile ions as the beam passes through solid matter. If the pulse length is
      assumed to be too long, substantial hydrodynamic expansion of the target material
      occurs during the early stages of irradiation that leads to significant reduction
      in the energy deposition by the ions that are delivered in the later part of the
      pulse. In case of the five-bunch configuration, heating caused by the first bunch
      is so strong that the target is completely distorted. As a result, the ions that
      are delivered in the later four bunches pass through the target without any
      interaction.

PMID- 11308776
TI  - Plasma perturbation induced by laser photodetachment.
AB  - The plasma dynamics arising from laser photodetachment is discussed herein
      theoretically and experimentally. The hybrid fluid-kinetic model, where the
      positive ions and electrons are treated by the fluid theory and the negative ions
      are treated within the ballistic approximation, is extended and applied to the
      analysis of densities perturbed by laser photodetachment. The agreement between
      the theory and measured data confirms the validity of the considered plasma
      dynamics model. This model, including the positive ion perturbation, shows a good
      agreement with the time evolution and the spatial distribution of perturbed
      electron densities which are measured by a Langmuir probe inside and outside the
      laser beam. From the overshoot in the time evolution of perturbed electron
      current in the center of the laser beam, the positive ion temperature was found
      to be in the range 0.1-0.25 eV, while the electron temperature changes from 0.3
      to 3.2 eV.

PMID- 11308777
TI  - Kinetic model of ionization waves in a positive column at intermediate pressures
      in inert gases.
AB  - A kinetic model of ionization waves in the inert gas discharge is constructed,
      which is based on the simultaneous solution of the kinetic equation for electrons
      and the continuity equations for ions and excited atoms. The model corresponds to
      a range of intermediate pressures and small currents, when elastic collisions
      dominate in the electron energy balance and electron-electron collisions are
      negligibly small. A linear theory of ionization waves is constructed, growth
      rates and frequencies of wave disturbances able to propagate in plasma are found.
      It is shown that there is an upper bound to the existence of striations by
      pressure, as well as the lower bound by current. The self-consistent solution of
      the source system of equations is obtained, which describes a nonlinear wave. The
      profile of electric field and the electron distribution function in this field
      are calculated. The results of calculations are compared with the experimental
      data. The wavelengths obtained are essentially larger than the electron energy
      relaxation length. Such waves cannot be described within the limits of fluid
      models.

PMID- 11308778
TI  - Hydrodynamic characteristics of transient Ni-like x-ray lasers.
AB  - A simple similarity model is presented to study the hydrodynamics of transient
      collisional excitation nickellike x-ray lasers. Scaling laws for the temperature,
      scale length, and electron density are obtained by analytic derivation. The
      hydrodynamic characteristics of transient Ni-like Pd x-ray lasers are
      investigated using this model. The calculations agree well with Dunn's
      experimental results.

PMID- 11308779
TI  - Stimulated electromagnetic shock radiation: classical second-order calculations.
AB  - By performing classical, relativistic, second-order calculations we have shown
      that simulated electromagnetic shock radiation (SESR) is given out as an
      enormously amplified, exponentially growing, frequency upshifted, highly
      directional coherent electromagnetic radiation. We have derived expressions
      specifying the electric field components of SESR in the most compact and readable
      form. Hence we have calculated the field amplitudes of SESR for different sets of
      external controlling parameters and plotted some typical results in the most
      sensitive region, viz., very near the threshold of superphase motion. We have
      also shown the variation of SESR with respect to external parameters graphically.
      The results obtained are of importance in achieving a tunable source of coherent
      radiation in the frequency region not covered by existing sources.

PMID- 11308780
TI  - Simulation and design of stable channel-guided laser wakefield accelerators.
AB  - Most laser wakefield accelerator (LWFA) experiments to date have operated in the
      self-modulated (SM) regime and have been self-guided. A channel-guided LWFA
      operating in the standard or resonant regime is expected to offer the possibility
      of high electron energy gain and high accelerating gradients without the
      instabilities and poor electron beam quality associated with the SM regime.
      Plasma channels such as those produced by a capillary discharge have demonstrated
      guiding of intense laser pulses over distances of several centimeters. Optimizing
      the performance in a resonant LWFA constrains the on-axis plasma density in the
      channel to a relatively narrow range. A scaling model is presented that
      quantifies resonant LFWA performance in terms of the maximum accelerating
      gradient, dephasing length, and dephasing-limited energy gain. These performance
      quantities are expressed in terms of laser and channel experimental parameters,
      clearly illustrating some of the tradeoffs in the choice of parameters. The
      predicted energy gain in this model is generally lower than that indicated by
      simpler scaling models. Simulations agree well with the scaling model in both low
      and high plasma density regimes. Simulations of a channel-guided, self-modulated
      LWFA are also presented. Compared with the resonant LWFA regime, the requirements
      on laser and channel parameters in the SM regime are easier to achieve, and a
      channel-guided SM-LWFA is likely to be less unstable than a self-guided SM-LWFA.

PMID- 11308781
TI  - Constraints on plasma compensation of beam-beam effects in muon colliders.
AB  - We obtain necessary conditions for the plasma compensation to work in muon
      colliders. To this end, we analyze the suppression of beam fields by the plasma,
      collisional diffusion of the return plasma current, possible beam filamentation,
      and dynamics of plasma ions. We show that a good compensation requires very short
      beams and allows little freedom in choice of the plasma density.

PMID- 11308782
TI  - Nonlinearity and disorder: classification and stability of nonlinear impurity
      modes.
AB  - We study the effects produced by competition of two physical mechanisms of energy
      localization in inhomogeneous nonlinear systems. As an example, we analyze
      spatially localized modes supported by a nonlinear impurity in the generalized
      nonlinear Schrodinger equation and describe three types of nonlinear impurity
      modes, one- and two-hump symmetric localized modes and asymmetric localized
      modes, for both focusing and defocusing nonlinearity and two different
      (attractive or repulsive) types of impurity. We obtain an analytical stability
      criterion for the nonlinear localized modes and consider the case of a power-law
      nonlinearity in detail. We discuss several scenarios of the instability-induced
      dynamics of the nonlinear impurity modes, including the mode decay or switching
      to a new stable state, and collapse at the impurity site.

PMID- 11308783
TI  - Soliton internal mode bifurcations: pure power law?
AB  - The bifurcation of internal solitary wave modes from the essential spectrum has
      been one of the most exciting recent developments in the study of soliton
      dynamics. To date, it was believed that the bifurcation of such modes due to
      discretization has a strict power law dependence on the lattice discreteness
      parameter. In this work we prove that this dependence actually possesses relevant
      exponentially small terms which distinguish between different solutions for the
      discrete models. The theoretical result is established by using a discrete
      version of the Evans function. The predictions presented herein compare very
      favorably with the numerical study of the linear eigenvalue problem, and offer
      explanations of computational effects not possible on the basis of previous
      theoretical studies.

PMID- 11308784
TI  - Twisted localized modes.
AB  - In a number of recent papers the so-called twisted localized mode of the discrete
      nonlinear Schrodinger equation has been proposed. Herein, we study the existence
      and stability properties of such modes. We analyze the persistence of
      quasiperiodic modes and study the domains of existence and numerical stability of
      the exact form of such solutions. We identify the bifurcations through which they
      lose their stability and follow the behavior of the intrinsic localized modes and
      their eigenmodes even in the unstable regime.

PMID- 11308785
TI  - Stability of multiple pulses in discrete systems.
AB  - The stability of multiple-pulse solutions to the discrete nonlinear Schrodinger
      equation is considered. A bound state of widely separated single pulses is
      rigorously shown to be unstable, unless the phase shift Delta phi between
      adjacent pulses satisfies Delta phi=pi. This instability is accounted for by
      positive real eigenvalues in the linearized system. The analysis leading to the
      instability result does not, however, determine the linear stability of those
      multiple pulses for which Delta phi=pi between adjacent pulses. A direct
      variational approach for a two-pulse predicts that it is linearly stable if Delta
      phi=pi, and if the separation between the individual pulses satisfies a certain
      condition. The variational approach can easily be generalized to study the
      stability of N pulses for any N>or=3. The analysis is supplemented with a
      detailed numerical stability analysis.

PMID- 11308786
TI  - Phase-induced stability in a parametric dimer.
AB  - We report results on a model of two coupled oscillators that undergo periodic
      parametric modulations with a phase difference straight theta. Being to a large
      extent analytically solvable, the model reveals a rich straight theta dependence
      of the regions of parametric resonance. In particular, the intuitive notion that
      antiphase modulations are less prone to parametric resonance is confirmed for
      sufficiently large coupling and damping. Some general results concerning
      synchronization properties in this system are presented. We also compare our
      results to a recently reported mean-field model of collective parametric
      instability, showing that the two-oscillator model captures much of the
      qualitative behavior of the infinite system.

PMID- 11308787
TI  - Localized electromagnetic and weak gravitational fields in the source-free space.
AB  - Localized electromagnetic and weak gravitational time-harmonic fields in the
      source-free space are treated using expansions in plane waves. The presented
      solutions describe fields having a very small (about several wavelengths) and
      clearly defined core region with maximum intensity of field oscillations. In a
      given Lorentz frame L, a set of the obtained exact time-harmonic solutions of the
      free-space homogeneous Maxwell equations consists of three subsets (storms,
      whirls, and tornados), for which time average energy flux is identically zero at
      all points, azimuthal and spiral, respectively. In any other Lorentz frame L',
      they will be observed as a kind of electromagnetic missile moving without
      dispersing at speed V<c. The solutions that describe finite-energy evolving
      electromagnetic storms, whirls, tornados, and weak gravitational fields with
      similar properties are also presented. The properties of these fields are
      illustrated in graphic form.

PMID- 11308788
TI  - Scattering of sound by a vorticity filament: an experimental and numerical
      investigation.
AB  - A vorticity filament is investigated experimentally using the transmission of an
      ultrasonic wave through the flow. The analysis of the wave-front distortion
      provides noninvasive measurements of the vortex circulation and size. The latter
      is estimated by analytical calculations of the scattering of a plane wave by a
      vorticity filament. The case of a cylindrical wave incident on a vortex leads to
      similar experimental results which are successfully compared to a parabolic
      equation simulation. Finally, a finite-difference code based on linear acoustics
      is presented, in order to investigate the structure of the scattered wave
      numerically.

PMID- 11308789
TI  - Measurement of the gain volume in amplifying and scattering media by a two-beam
      spatial-correlation method.
AB  - We measured the size of the gain volume at the threshold of the spectral collapse
      in a solution of kiton red with colloidal suspensions of polystyrene spheres
      using a two-beam spatial-correlation method. In this method, the luminescence
      spectrum was measured as a function of the spatial separation of two excitation
      beams. It was found that the size of the gain volume at the threshold L(th), is
      proportional to the absorption length L(a), for different samples. Numerical
      simulations are also presented and the results are discussed on the basis of a
      relation L(th)=sqrt[3G(th)]sqrt[sigma(a)/sigma(s)]L(a), where sigma(s) and
      sigma(a) are stimulated emission and absorption cross sections of kiton red,
      respectively.

PMID- 11308790
TI  - Dynamics of a charged particle in a linearly polarized traveling electromagnetic
      wave.
AB  - The relativistic motion of a charged particle in a linearly polarized homogeneous
      electromagnetic wave is studied using the Hamiltonian formalism. First, a single
      particle in a linearly polarized traveling wave propagating in a nonmagnetized
      space is studied. It is shown that the charged particle can have a high average
      velocity along the propagation direction of the wave. The same result is derived
      considering an electromagnetic wave in a cold electron plasma. The case of a
      traveling wave propagating along a constant homogeneous magnetic field is then
      considered and shown to be nonintegrable. Using canonical transformations, it is
      shown that the equations of motion can be derived from an autonomous Hamiltonian
      and a formal solution is found for all the variables of the system. Considering
      that the wave propagates in vacuum and the particle is initially resonant and at
      rest, a set of equations is found coupling the energy of the particle and the
      phase of the wave. Then, the expression for the energy and the differential
      equation for the phase allow a solution in terms of quadratures. Finally,
      asymptotic solutions for the phase, the energy and consequently all of the
      variables are found.

PMID- 11308791
TI  - Group velocity, energy velocity, and superluminal propagation in finite photonic
      band-gap structures.
AB  - We have analyzed the notions of group velocity V(g) and energy velocity V(E) for
      light pulses propagating inside one-dimensional photonic band gap structures of
      finite length. We find that the two velocities are related through the
      transmission coefficient t as V(E)=/t/(2)V(g). It follows that V(E)=V(g) only
      when the transmittance is unity (/t/(2)=1). This is due to the effective
      dispersive properties of finite layered structures, and it allows us to better
      understand a wide range of phenomena, such as superluminal pulse propagation. In
      fact, placing the requirement that the energy velocity should remain subluminal
      leads directly to the condition V(g)<or=c//t/(2). This condition places a large
      upper limit on the allowed group velocity of the tunneling pulse at frequencies
      of vanishingly small transmission.

PMID- 11308793
TI  - Stability of repulsive Bose-Einstein condensates in a periodic potential.
AB  - The cubic nonlinear Schrodinger equation with repulsive nonlinearity and an
      elliptic function potential models a quasi-one-dimensional repulsive dilute gas
      Bose-Einstein condensate trapped in a standing light wave. New families of
      stationary solutions are presented. Some of these solutions have neither an
      analog in the linear Schrodinger equation nor in the integrable nonlinear
      Schrodinger equation. Their stability is examined using analytical and numerical
      methods. All trivial-phase stable solutions are deformations of the ground state
      of the linear Schrodinger equation. Our results show that a large number of
      condensed atoms is sufficient to form a stable, periodic condensate. Physically,
      this implies stability of states near the Thomas-Fermi limit.

PMID- 11308792
TI  - Isomeric photonic molecules formed from coupled microresonators.
AB  - Isomeric photonic molecules were formed by connecting four identical cavities in
      different geometries: a chain, a square, and a T shape. The optical mode spectrum
      in these structures exhibits three-dimensionally confined photonic states, which
      have been studied by photoluminescence spectroscopy. The energies of the optical
      modes depend strongly on the molecule geometry. The experimental data are in good
      agreement with detailed calculations of the fields in the cavities.

PMID- 11308794
TI  - Dichromatic nonlinear eigenmodes in slab waveguide with chi(2) nonlinearity.
AB  - The existence of purely nonlinear eigenmodes in a waveguiding structure composed
      of a slab with quadratic nonlinearity surrounded by (non)linear claddings is
      reported. Modes having bright and dark solitonlike shapes and consisting of two
      mutually locked harmonics are identified. Asymmetrical modes are shown to exist
      in symmetrical environments. Constraints for the existence of the modes are
      derived in terms of parameters of guiding structure materials.

PMID- 11308795
TI  - Radiative losses due to pulse interactions in birefringent nonlinear optical
      fibers.
AB  - The transient evolution of two-polarization pulses in a birefringent nonlinear
      optical fiber, governed by coupled nonlinear Schrodinger (NLS) equations, is
      considered. The evolution is studied using a trial function consisting of coupled
      solitonlike pulses with varying parameters augmented by a radiative shelf in the
      Lagrangian formulation of the coupled equations, which yields ordinary
      differential equations for the pulse parameters. It is shown that including mass
      and momentum fluxes due to the radiative shelf is a requirement to obtain good
      agreement with full numerical solutions of the governing equations.

PMID- 11308796
TI  - Viscous flow and jump dynamics in molecular supercooled liquids. I. Translations.
AB  - The transport and relaxation properties of a molecular supercooled liquid on an
      isobar are studied by molecular dynamics. The molecule is a rigid heteronuclear
      biatomic system. The diffusivity is fitted over four orders of magnitude by the
      power law D proportional to (T-T(c))(gamma(D)), with gamma(D)=1.93+/-0.02 and
      T(c)=0.458+/-0.002. The self-part of the intermediate scattering function
      F(s)(k(max),t) exhibits a steplike behavior at the lowest temperatures. On
      cooling, the increase of the related relaxation time tau(alpha) tracks the
      diffusivity, i.e., tau(alpha) proportional to (k(2)(max)D)(-1). At the lowest
      temperatures, fractions of highly mobile and trapped molecules are also
      evidenced. Translational jumps are also evidenced. The duration of the jumps
      exhibits a distribution. The distribution of the waiting times before a jump
      takes place, psi(t), is exponential at higher temperatures. At lower temperatures
      a power-law divergence is evidenced at short times, psi(t) proportional to t(xi
      1) with 0<xi<or=1, which is ascribed to intermittency. The shear viscosity is
      fitted by the power law eta proportional to (T-T(c))(gamma(eta)), with
      gamma(eta)=-2.20+/-0.03 at the lowest temperatures. At higher temperatures the
      Stokes-Einstein relation fits the data if stick boundary conditions are assumed.
      The product D eta/T increases at lower temperatures, and the Stokes-Einstein
      relation breaks down at a temperature which is close to the one where the
      intermittency is evidenced by psi(t). A precursor effect of the breakdown is
      observed, which manifests itself as an apparent stick-slip transition.

PMID- 11308797
TI  - Viscous flow and jump dynamics in molecular supercooled liquids. II. Rotations.
AB  - The rotational dynamics of a supercooled model liquid of rigid A-B dumbbells
      interacting via a Lennard-Jones potential is investigated along one single
      isobar. The time-temperature superposition principle, one key prediction of mode
      coupling theory (MCT), was studied for the orientational correlation functions
      C(l). In agreement with previous studies we found that the scaling of C(l) in a
      narrow region at long times is better at high-l values. However, on a wider time
      interval the scaling works fairly better at low-l values. Consistently, we
      observed the remarkable temperature dependence of the rotational correlation time
      tau(1) as a power law in T-T(c) over more than three orders of magnitude and the
      increasing deviations from that law on increasing l (T(c) is the MCT critical
      temperature). For 0.7<T<2, good agreement with the diffusion model is found. For
      lower temperatures the agreement becomes poorer, and the results are also only
      partially accounted for by the jump-rotation model. The angular Van Hove function
      shows that in this region a meaningful fraction of the sample reorientates by
      jumps of about 180 degrees. The distribution of the waiting times in the angular
      sites cuts exponentially at long times. At lower temperatures it decays at short
      times as t(xi-1), with xi=0.34+/-0.04 at T=0.5, in analogy with the translational
      case. The breakdown of the Debye-Stokes-Einstein relation is observed at lower
      temperatures, where the rotational correlation times diverge more weakly than the
      viscosity.

PMID- 11308798
TI  - Three-dimensional optical trajectory tracing and energy deposition of a laser
      beam in a laser-driven fusion.
AB  - A convenient method of three-dimensional ray tracing is suggested in the
      geometrical optical approximation, in which the laser ray propagation is
      completely based on the concept of optical trajectory tracing rather than
      depending upon the effective force and propagation time. This tracing has two
      obvious advantages that the direct application of Snell's law can be avoided when
      a ray crosses a different density zone and that to any desired accuracy it takes
      much less computation time than existing tracing. For Gaussian light beam
      propagation, in a spherically symmetric plasma atmosphere, the results emphasize
      that the deposition uniformity is strongly dependent not only on the wavelength
      of the laser but also on the temperature of the plasma.

PMID- 11308799
TI  - Critical behavior of the long-range Ising chain from the largest-cluster
      probability distribution.
AB  - Monte Carlo simulations of the one-dimensional Ising model with ferromagnetic
      interactions decaying with distance r as 1/r(1+sigma) are performed by applying
      the Swendsen-Wang cluster algorithm with cumulative probabilities. The critical
      behavior in the nonclassical critical regime corresponding to 0.5<sigma<1 is
      derived from finite-size scaling analysis of the largest cluster.

PMID- 11308800
TI  - Unified optimization criterion for energy converters.
AB  - We propose a unified optimization criterion for energy converters. It represents
      the best compromise between energy benefits and losses for a specific job and
      neither an explicit evaluation of entropies nor the consideration of
      environmental parameters are required. For all considered systems the criterion
      predicts a performance regime laying between those of maximum efficiency and
      maximum useful energy. Such regime has been invoked as optimum not only in
      macroscopic heat engines but also in some molecular motors.

PMID- 11308801
TI  - Quantum phase transitions and the extended coupled cluster method.
AB  - We discuss the application of an extended version of the coupled cluster method
      to systems exhibiting a quantum phase transition. We use the lattice O(4)
      nonlinear sigma model in (1+1) and (3+1) dimensions as an example. We show how
      simple predictions get modified, leading to the absence of a phase transition in
      (1+1) dimensions, and strong indications for a phase transition in (3+1)
      dimensions.

PMID- 11308802
TI  - Two-step melting transition in confined hard spheres in three dimensions.
AB  - It is shown that certain geometrical constraints on a system of hard spheres lead
      to two distinct finite-size analogs of melting transitions upon decreasing the
      average number of spheres at constant volume. Melting takes place from an ordered
      crystal via an intermediate structure to a fluid. Sphere centers in the
      intermediate state have a high probability to be found in localized regions that
      are dramatically different in size and shape.

PMID- 11308803
TI  - Spectral oscillations in a frequency-modulation laser operation.
AB  - We show the existence of coherent oscillations in the optical frequency spectrum
      of a laser with internal frequency modulation. These oscillations arise in
      presence of a slight detuning between the modulation frequency and the cavity
      axial mode separation and are analogous to collective oscillation modes of a
      chain of weakly coupled pendula with resonance frequencies slightly varying along
      the chain. Although spectral oscillations are damped due to the finite gain
      bandwidth of the laser cavity, they can be observed in the transient dynamics
      during switch-on of the modulator, or can be resonantly excited by an external
      forcing.

PMID- 11308804
TI  - Two-dimensional type-I intermittency.
AB  - The general structure of two-dimensional intermittency is discussed. The
      structure of channel and the trajectory in the return map are compared with those
      of one-dimensional intermittency and the scaling relations are obtained according
      to the trajectory. We illustrate the temporal behavior and scaling relations in a
      coupled map. The numerical results agree well with the theoretical predication of
      <l> approximately equal 1/sqrt[epsilon].

PMID- 11308805
TI  - Invisible mean field dynamos.
AB  - We provide examples of alpha(2) dynamos in spheres which generate magnetic fields
      that are confined to the conductor and are therefore undetectable in the
      surrounding vacuum.

PMID- 11308806
TI  - Interaction of an electromagnetic wave packet with an ionization front:
      copropagating configuration.
AB  - The interaction of a TM polarized wave packet with a moving ionization front is
      theoretically investigated. We extend our previous study [IEEE Trans. Plasma Sci.
      27, 655 (1999)], where we considered the case when the wave packet is incident on
      the front, by including the case often used in experiments when the front
      overtakes the wave packet. We focus on the energy transformation into the
      generated waves-the point that is rarely addressed in literature due to
      complications arising from the presence of Langmuir waves. Our quantitative
      results show the importance of losses via Langmuir wave excitation compared to
      other possible losses due to the excitation of stationary transverse electron
      currents in the plasma. Applicability to the generation of frequency upshifted
      radiation is discussed.

PMID- 11308807
TI  - Bounds on the length of magnetic field lines in a two-dimensional plasma.
AB  - Magnetic field lines in ideal turbulent plasmas tend to become quite complicated
      and their length to grow in time. Diffusivity allows for reconnection and
      possible shortening, but this fact has not so far been rigorously quantified. We
      show that in a two-dimensional diffusive plasma the mean length of field lines
      stays bounded for all time. Moreover, these estimates are local, in the sense
      that the mean values of magnetic field and velocity in the neighborhood of a ball
      determine bounds for length within the ball, without recourse to external
      magnitudes.

PMID- 11308808
TI  - Decay of discrete nonlinear Schrodinger breathers through inelastic multiphonon
      scattering.
AB  - We consider the long-time evolution of weakly perturbed discrete nonlinear
      Schrodinger breathers. While breather growth can occur through nonlinear
      interaction with one single initial linear mode, breather decay is found to
      require excitation of at least two independent modes. All growth and decay
      processes of lowest order are found to disappear for breathers larger than a
      threshold value.

PMID- 11308809
TI  - Phase retrieval from images in the presence of first-order vortices.
AB  - We discuss retrieval of the phase of quantum-mechanical and classical wave fields
      in the presence of first-order vortices. A practical method of phase retrieval is
      demonstrated which is robust in the presence of noise. Conditions for the
      uniqueness of the retrieved phase are discussed and we show that determination of
      the phase in a given plane requires a series of at least three two-dimensional
      intensity images at different propagation distances. The method is applicable to
      a wide range of scenarios such as the imaging of imperfect crystals, quantitative
      determination of the strength of vortex filaments in high-temperature
      superconductors, and x-ray and electron holography.

PMID- 11308810
TI  - Ermakov-Lewis angles for one-parameter supersymmetric families of Newtonian free
      damping modes.
AB  - We apply the Ermakov-Lewis procedure to the one-parameter damped modes y recently
      introduced by Rosu and Reyes, which are related to the common Newtonian free
      damping modes y by the general Riccati solution [H. C. Rosu and M. Reyes, Phys.
      Rev. E 57, 4850 (1998)]. In particular, we calculate and plot the angle
      quantities of this approach that can help to distinguish these modes from the
      common y modes.

PMID- 11308811
TI  - Quantum-fluctuation-induced spatial stochastic resonance at zero temperature.
AB  - We consider a model in which the quantum fluctuation can be controlled and show
      that the system responds to a spatially periodic external field at zero
      temperature. This signifies the occurrence of spatial stochastic resonance where
      the fluctuations are purely quantum in nature. Various features of the phenomenon
      are discussed.

PMID- 11308812
TI  - Steady state of microemulsions in shear flow.
AB  - Steady-state properties of microemulsions in shear flow are studied in the
      context of a Ginzburg-Landau free-energy approach. Explicit expressions are given
      for the structure factor and the time correlation function at the one-loop level
      of approximation. Our results predict a four-peak pattern for the structure
      factor, implying the simultaneous presence of interfaces aligned with two
      different orientations. Due to the peculiar interface structure a nonmonotonous
      relaxation of the time correlator is also found.

PMID- 11308813
TI  - Single molecule tracking of heterogeneous diffusion.
AB  - The mean square displacement of heterogeneous diffusion obeys the Einstein
      relation, thereby showing no sign of heterogeneities in the ensemble measurement
      of the diffusion constant. The signature of spatial heterogeneities appears in
      the time evolution of the non-Gaussian distribution and in the cross correlation
      between the square displacements at different times, both available from single
      molecule diffusional trajectories. As a quantitative measure, the non-Gaussian
      indicator g(t) decays asymptotically to zero according to 1/t for finite time
      correlation, but saturates at a plateau value for power-law correlation. In
      addition, the joint moment correlation function f(t,tau) provides a direct probe
      of the memory effect of the fluctuating rate constant. A two-state diffusion
      model and a stochastic Gaussian model are constructed to evaluate these
      quantities and are shown to yield the same result within the second cumulant
      expansion.

PMID- 11308814
TI  - Nonlinear reactive systems on a lattice viewed as Boolean dynamical systems.
AB  - We present a stochastic, time-discrete Boolean model that mimics the mesoscopic
      dynamics of the desorption reactions A+A-->A+S and A+A-->S+S in a one-dimensional
      lattice. In the continuous-time limit, we derive a hierarchy of dynamical
      equations for the subset of moments involving contiguous lattice sites. The
      solution of the hierarchy allows to compute the exact dynamics of the mean
      coverage for both microscopic and coarse-grained initial conditions, which turn
      out to be different from the mean field predictions. The evolution equations for
      the mean coverage and the second-order moments are shown to be equivalent to
      those provided by a time-continuous master equation. The important role of higher
      order fluctuations is brought out by the failure of a truncation scheme retaining
      only two-particle fluctuation correlations.

PMID- 11308815
TI  - Non-Hermitian delocalization from Hermitian Hamiltonians.
AB  - Here we show that using Galilean transformations the non-Hermitian delocalization
      phenomenon, which is relevant in different fields, such as bacteria population
      (e.g., Bacillus subtilis), vortex pinning in superconductors, and stability
      solutions of hydrodynamical problems discovered by Hatano and Nelson [Phys. Rev.
      Lett. 77, 5706 (1996)], can be obtained from solutions of the time-dependent
      Schrodinger equation with a Hermitian Hamiltonian. Using our approach, one avoids
      the numerical complications and instabilities which result form the calculations
      of left and right eigenfunctions of the non-Hermitian Hamiltonian which are
      associated with the non-Hermitian delocalization phenomenon. One also avoids the
      need to replace the non-Hermitian Hamiltonian H by a supermatrix with twice the
      dimension of H, where the complex frequencies serve as variational parameters
      rather than eigenvalues of H.

PMID- 11308816
TI  - Random spread on the family of small-world networks.
AB  - We present analytical and numerical results of a random walk on the family of
      small-world graphs. The average access time shows a crossover from regular to
      random behavior with increasing distance from the starting point of the random
      walk. We introduce an independent step approximation, which enables us to obtain
      analytic results for the average access time. We observe a scaling relation for
      the average access time in the degree of the nodes. The behavior of the average
      access time as a function of p shows striking similarity with that of the
      characteristic length of the graph. This observation may have important
      applications in routing and switching in networks with a large number of nodes.

PMID- 11308817
TI  - Multifractal characterization of stochastic resonance.
AB  - We use a multifractal formalism to study the effect of stochastic resonance in a
      noisy bistable system driven by various input signals. To characterize the
      response of a stochastic bistable system we introduce a new measure based on the
      calculation of a singularity spectrum for a return time sequence. We use wavelet
      transform modulus maxima method for the singularity spectrum computations. It is
      shown that the degree of multifractality defined as a width of singularity
      spectrum can be successfully used as a measure of complexity both in the case of
      periodic and aperiodic (stochastic or chaotic) input signals. We show that in the
      case of periodic driving force, singularity spectrum can change its structure
      qualitatively becoming monofractal in the regime of stochastic synchronization.
      This fact allows us to consider the degree of multifractality as a new measure of
      stochastic synchronization also. Moreover, our calculations have shown that the
      effect of stochastic resonance can be catched by this measure even from a very
      short return time sequence. We use also the proposed approach to characterize the
      noise-enhanced dynamics of a coupled stochastic neurons model.

PMID- 11308818
TI  - Magnetic fluctuations in the classical XY model: the origin of an exponential
      tail in a complex system.
AB  - We study the probability density function for the fluctuations of the magnetic
      order parameter in the low-temperature phase of the XY model of finite size. In
      two dimensions, this system is critical over the whole of the low-temperature
      phase. It is shown analytically and without recourse to the scaling hypothesis
      that, in this case, the distribution is non-Gaussian and of universal form,
      independent of both system size and critical exponent eta. An exact expression
      for the generating function of the distribution is obtained, which is transformed
      and compared with numerical data from high-resolution molecular dynamics and
      Monte Carlo simulations. The asymptotes of the distribution are calculated and
      found to be of exponential and double exponential form. The calculated
      distribution is fitted to three standard functions: a generalization of Gumbel's
      first asymptote distribution from the theory of extremal statistics, a
      generalized log-normal distribution, and a chi(2) distribution. The calculation
      is extended to general dimension and an exponential tail is found in all
      dimensions less than 4, despite the fact that critical fluctuations are limited
      to D=2. These results are discussed in the light of similar behavior observed in
      models of interface growth and for dissipative systems driven into a
      nonequilibrium steady state.

PMID- 11308819
TI  - Noninvasive control of stochastic resonance.
AB  - External feedback can enhance (or depress) the response of a noisy bistable
      system to monochromatic signals, significantly magnifying its natural stochastic
      resonance. We compare and contrast a variety of such feedback strategies, using
      both numerical simulations and analog electronic experiments. These noninvasive
      control techniques are especially valuable for noisy bistable systems that are
      difficult or impossible to modify internally.

PMID- 11308820
TI  - Target problem on small-world networks.
AB  - In this work we focus on reactions on small-world networks (SWN's), disordered
      graphs of much recent interest. We study the target problem, since it allows an
      exact solution on regular lattices. On SWN's we find that the decay of the
      targets (for which we extend the formalism to disordered lattices) is again
      related to S(n), the mean number of distinct sites visited in n steps, although
      the S(n) vs n dependence changes here drastically in going from regular linear
      chains to their SWN.

PMID- 11308821
TI  - One-dimensional contact process: duality and renormalization.
AB  - We study the one-dimensional contact process in its quantum version using a
      recently proposed real-space renormalization technique for stochastic many
      particle systems. Exploiting the duality and other properties of the model, we
      can apply the method for cells with up to 37 sites. After suitable extrapolation,
      we obtain exponent estimates that are comparable in accuracy with the best known
      in the literature.

PMID- 11308822
TI  - Constructive role of temperature in ratchets driven by trichotomous noise.
AB  - The dynamics of an overdamped Brownian particle in a piecewise linear spatially
      periodic potential subjected to both thermal and colored symmetric three-level
      Markovian (trichotomous) noises is investigated. In the case of large flatness,
      the exact formula for the stationary current is presented. The dependence of the
      current on the system parameters is analyzed and the conditions for the
      occurrence of current reversals are found. It is shown that the direction and
      value of the current can be controlled by a thermal noise. Asymptotic formulas
      for the current for various limits of the noise parameters are calculated and
      compared with the results of other authors. For small noise amplitudes, it is
      demonstrated that the temperature at which the current is maximized is
      proportional to the height of the potential barrier, being a slowly varying
      function of the other system parameters.

PMID- 11308823
TI  - Thermodynamically self-consistent theory for the Blume-Capel model.
AB  - We use a self-consistent Ornstein-Zernike approximation to study the Blume-Capel
      ferromagnet on three-dimensional lattices. The correlation functions and the
      thermodynamics are obtained from the solution of two coupled partial differential
      equations. The theory provides a comprehensive and accurate description of the
      phase diagram in all regions, including the wing boundaries in a nonzero magnetic
      field. In particular, the coordinates of the tricritical point are in very good
      agreement with the best estimates from simulation or series expansion. Numerical
      and analytical analysis strongly suggest that the theory predicts a universal
      Ising-like critical behavior along the lambda line and the wing critical lines,
      and a tricritical behavior governed by mean-field exponents.

PMID- 11308824
TI  - Stochastic resonance in a suspension of magnetic dipoles under shear flow.
AB  - We show that a magnetic dipole in a shear flow under the action of an oscillating
      magnetic field displays stochastic resonance in the linear response regime. To
      this end, we compute the classical quantifiers of stochastic resonance, i.e., the
      signal to noise ratio, the escape time distribution, and the mean first passage
      time. We also discuss the limitations and role of the linear response theory in
      its applications to the theory of stochastic resonance.

PMID- 11308825
TI  - Discrete atomistic model to simulate etching of a crystalline solid.
AB  - A discrete atomistic solid-on-solid model is proposed to describe dissolution of
      a crystalline solid by a liquid. The model is based on the simple assumption that
      the probability per unit time of a unit cell being removed is proportional to its
      exposed area. Numerical simulations in one dimension demonstrate that the model
      has very good scaling properties. After removal of only about 10(2) monolayers,
      independently of the substrate size, the etched surface shows almost time
      independent short-range correlations and the receding surface presents the Family
      Vicsek scaling behavior. The scaling parameters alpha=0.491+/-0.002 and
      beta=0.330+/-0.001 indicate that the system belongs to the Kardar-Parisi-Zhang
      universality class. The imposition of periodic boundary conditions on the
      simulations reduces the effective system size by a factor of 0.68 without
      changing the exponents alpha and beta. Surprisingly, the periodic condition
      changes drastically the statistics of the surface height fluctuations and the
      short-range correlations. Without periodic conditions, that statistics is, up to
      3 standard deviations, an asymmetric Levy distribution with mu=1.82+/-0.01, and
      outside this region the statistics is Gaussian. With periodic conditions, that
      statistics is Gaussian, except for large negative fluctuations.

PMID- 11308826
TI  - Information transmission in parallel threshold arrays: suprathreshold stochastic
      resonance.
AB  - The information transmitted through a parallel summing array of noisy threshold
      elements with a common threshold is considered. In particular, using theoretical
      and numerical analysis, a recently reported [N. G. Stocks, Phys. Rev. Lett. 84,
      2310 (2000)] form of stochastic resonance, termed suprathreshold stochastic
      resonance (SSR), is studied in detail. SSR is observed to occur in arrays with
      two or more elements and, unlike stochastic resonance (SR) in a single element,
      gives rise to noise-induced information gains that occur independent of the
      setting of the threshold or the size of the signal. The transmitted information
      is maximized when all thresholds are set to coincide with the signal mean. In
      this situation, and for large arrays, the noise can enhance performance up to
      approximately half the theoretical noiseless channel capacity. The theory is
      tested against digital simulation.

PMID- 11308827
TI  - Transition from anomalous to normal hysteresis in a system of coupled Brownian
      motors: a mean-field approach.
AB  - We address a recently introduced model describing a system of periodically
      coupled nonlinear phase oscillators submitted to multiplicative white noises,
      wherein a ratchetlike transport mechanism arises through a symmetry-breaking
      noise-induced nonequilibrium phase transition. Numerical simulations of this
      system reveal amazing novel features such as negative zero-bias conductance and
      anomalous hysteresis, explained by performing a strong-coupling analysis in the
      thermodynamic limit. Using an explicit mean-field approximation, we explore the
      whole ordered phase finding a transition from anomalous to normal hysteresis
      inside this phase, estimating its locus, and identifying (within this scheme) a
      mechanism whereby it takes place.

PMID- 11308828
TI  - Branching and annihilating Levy flights.
AB  - We consider a system of particles undergoing the branching and annihilating
      reactions A-->(m+1)A and A+A-->O, with m even. The particles move via long-range
      Levy flights, where the probability of moving a distance r decays as r(-d-sigma).
      We analyze this system of branching and annihilating Levy flights using field
      theoretic renormalization group techniques close to the upper critical dimension
      d(c)=sigma with sigma<2. These results are then compared with Monte Carlo
      simulations in d=1. For sigma close to unity in d=1, the critical point for the
      transition from an absorbing to an active phase occurs at zero branching.
      However, for sigma bigger than about 3/2 in d=1, the critical branching rate
      moves away from zero with increasing sigma, and the transition lies in a
      different universality class, inaccessible to controlled perturbative expansions.
      We measure the exponents in both universality classes and examine their behavior
      as a function of sigma.

PMID- 11308829
TI  - Thermodynamic and structural aspects of the potential energy surface of simulated
      water.
AB  - Relations between the thermodynamics and dynamics of supercooled liquids
      approaching a glass transition is a topic of considerable interest. The potential
      energy surface of model liquids has been increasingly studied, since it provides
      a connection between the configurational component of the partition function on
      the one hand, and the system dynamics on the other. This connection is most
      obvious at low temperatures, where the motion of the system can be partitioned
      into vibrations within a basin of attraction and infrequent interbasin
      transitions. In this work, we present a description of the potential energy
      surface properties of supercooled liquid water. The dynamics of this model have
      been studied in great detail in recent years. We locate the minima sampled by the
      liquid by "quenches" from equilibrium configurations generated via molecular
      dynamics simulations, and then calculate the temperature and density dependence
      of the basin energy, degeneracy, and shape. The temperature dependence of the
      energy of the minima is qualitatively similar to simple liquids, but has
      anomalous density dependence. The unusual density dependence is also reflected in
      the configurational entropy, the thermodynamic measure of degeneracy. Finally, we
      study the structure of simulated water at the minima, which provides insight on
      the progressive tetrahedral ordering of the liquid on cooling.

PMID- 11308830
TI  - Waterlike anomalies for core-softened models of fluids: two-dimensional systems.
AB  - We use molecular-dynamics simulations in two dimensions to investigate the
      possibility that a core-softened potential can reproduce static and dynamic
      anomalies found experimentally in liquid water: (i) the increase in specific
      volume upon cooling, (ii) the increase in isothermal compressibility upon
      cooling, and (iii) the increase in the diffusion coefficient with pressure. We
      relate these anomalies to the shape of the potential. We obtain the phase diagram
      of the system and identify two solid phases: a square crystal (high-density
      phase) and a triangular crystal (low-density phase). We also discuss the relation
      between the anomalies observed and the polymorphism of the solid. Finally, we
      compare the phase diagram of our model system with experimental data, noting
      especially the line of temperatures of maximum density, the line of pressures of
      maximum diffusion constant, and the line of temperatures of minimum isothermal
      compressibility.

PMID- 11308831
TI  - Structure and effective interactions in three-component hard sphere liquids.
AB  - Complete and simple analytical expressions for the partial structure factors of
      the ternary hard sphere mixture are obtained within the Percus-Yevick
      approximation and presented as functions of relative packing fractions and
      relative hard sphere diameters. These solutions follow from the Laplace transform
      method as applied to multicomponent systems by Lebowitz [Phys. Rev. 133, A895
      (1964)]. As an important application, we examine effective interactions in hard
      sphere liquid mixtures using the microscopic information contained in their
      partial structure factors. Thus the ensuring pair potential for an effective one
      component system is obtained from the correlation functions by using an
      approximate inversion, and examples of effective potentials for three-component
      hard sphere mixtures are given. These mixtures may be of particular interest for
      the study of the packing aspects of melts that form glasses or quasicrystals,
      since noncrystalline solids often emerge from melts with at least three atomic
      constituents.

PMID- 11308832
TI  - Stress transmission through textured granular packings.
AB  - We propose a theoretical approach aimed to describe the stress transmission
      through granular pilings. According to our framework, the stress transmission
      obeys a diffusive process in random isotropic packings, while it follows a local
      convection-diffusion equation in textured packings characterized by an
      anisotropic distribution of the contact orientations. In the latter case, the
      direction of the convection depends on the angular distribution function of the
      contact orientations. Our theoretical approach agrees with both experimental and
      numerical recent evidences, and moreover, succeeds in capturing the role of the
      pile preparing history.

PMID- 11308833
TI  - Clustering and fluidization in a one-dimensional granular system: molecular
      dynamics and direct-simulation Monte Carlo method.
AB  - We study a one-dimensional granular gas of pointlike particles not subject to
      gravity between two walls at temperatures T(left) and T(right). The system
      exhibits two distinct regimes, depending on the normalized temperature difference
      Delta=(T(right)-T(left))/(T(right)+T(left)): one completely fluidized and one in
      which a cluster coexists with the fluidized gas. When Delta is above a certain
      threshold, cluster formation is fully inhibited, obtaining a completely fluidized
      state. The mechanism that produces these two phases is explained. In the
      fluidized state the velocity distribution function exhibits peculiar non-Gaussian
      features. For this state, comparison between integration of the Boltzmann
      equation using the direct-simulation Monte Carlo method and results stemming from
      microscopic Newtonian molecular dynamics gives good coincidence, establishing
      that the non-Gaussian features observed do not arise from the onset of
      correlations.

PMID- 11308834
TI  - Statistical mechanics of fluidized granular media: short-range velocity
      correlations.
AB  - A statistical mechanical study of fluidized granular media is presented. Using a
      special energy injection mechanism, homogeneous fluidized stationary states are
      obtained. Molecular dynamics simulations and theoretical analysis of the
      inelastic hard-disk model show that there is a large asymmetry in the two
      particle distribution function between pairs that approach and separate. Large
      velocity correlations appear in the postcollisional states due to the dissipative
      character of the collision rule. These correlations can be well-characterized by
      a state dependent pair correlation function at contact. It is also found that
      velocity correlations are present for pairs that are about to collide. Particles
      arrive at collisions with a higher probability that their velocities are parallel
      rather than antiparallel. These dynamical correlations lead to a decrease of the
      pressure and of the collision frequency as compared to their Enskog values. A
      phenomenological modified equation of state is presented.

PMID- 11308835
TI  - Force distributions in three-dimensional granular assemblies: effects of packing
      order and interparticle friction.
AB  - We present a systematic investigation of the distribution of normal forces at the
      boundaries of static packings of spheres. A method for the efficient construction
      of large hexagonal-close-packed crystals is introduced and used to study the
      effect of spatial ordering on the distribution of forces. Under uniaxial
      compression we find that the form for the probability distribution of normal
      forces between particles does not depend strongly on crystallinity or
      interparticle friction. In all cases the distribution decays exponentially at
      large forces and shows a plateau or possibly a small peak near the average force
      but does not tend to zero at small forces.

PMID- 11308836
TI  - Spiral patterns in oscillated granular layers.
AB  - Cell-filling spiral patterns are observed in a vertically oscillated layer of
      granular material when the oscillation amplitude is suddenly increased from below
      the onset of pattern formation into the region where stripe patterns appear for
      quasistatic increases in amplitude. These spirals are transients and decay to
      stripe patterns with defects. A transient spiral defect chaos state is also
      observed. We describe the behavior of the spirals, and the way in which they form
      and decay. Our results are compared with those for similar spiral patterns in
      Rayleigh-Benard convection in fluids.

PMID- 11308837
TI  - Charge inversion of colloidal particles in an aqueous solution: screening by
      multivalent ions.
AB  - We investigate the structure of the electric double layer on charged colloids by
      Monte Carlo simulations. Using the primitive model of asymmetric electrolytes,
      the integrated charge distribution function on a spherical colloidal particle are
      also studied. With high concentrations of divalent ions, numerical results
      predict charge oscillation and charge inversion phenomena, which the traditional
      Derjaguin-Landau-Verwey-Overbeek theory cannot reproduce.

PMID- 11308838
TI  - Dynamical fluctuation of the mesoscopic structure in ternary C12E5-water-n-octane
      amphiphilic system.
AB  - Dynamical fluctuations of the bicontinuous microemulsion and lamellar structures
      in ternary C12E5-water-n-octane amphiphilic system are studied by means of
      neutron spin echo (NSE) spectrometry. The decay rates of the time correlation of
      the concentration were analyzed in terms of three theories: (1) A. G. Zilman and
      R. Granek, Phys. Rev. Lett. 77, 4788 (1996), (2) M. Nonomura and T. Ohta, J.
      Chem. Phys. 110, 7516 (1999), and (3) R. Granek and M. E. Cates, Phys. Rev. A 46,
      3319 (1992), in the first of which a Langevin equation for membrane plaquettes
      and in the latter two of which time-dependent Ginzburg-Landau equations for the
      order parameters are considered. The result shows that the intermediate
      correlation functions I(q,t) for the ranges of 0<t<15 ns and 0<q<0.2 A (-1) are
      well fitted to a stretched exponential function in time, I(q,t)=exp[
      (Gammat)(2/3)], for the bicontinuous microemulsion and the lamellar phases of the
      same systems with the relaxation rate Gamma increasing as q(3) in agreement with
      theory (1) from which the bending modulus of the membrane kappa was estimated.
      For more restricted ranges of 0<t<5 ns and 0.05<q<0.15 A (-1) the NSE result can
      be expressed by an exponential function in time in agreement with theory (2)
      determined exclusively by hydrodynamic interactions and for extended range of
      0<t<10 ns and 0.03<q<0.15 A (-1) by a nonexponential function in agreement with
      theory (3), from both of which the effective viscosities eta(0) and eta(eff) of
      the system were estimated. The effective viscosity from the nonexponential
      eta(eff) is five times greater than that from the simple exponential eta(0) that
      is almost the same as the literature value. The implication of this result is
      discussed in terms of the effective viscosity eta(eff) that takes into account
      the renormalization of the bending modulus of the membrane.

PMID- 11308839
TI  - Influence of solvent granularity on the effective interaction between charged
      colloidal suspensions.
AB  - We study the effect of solvent granularity on the effective force between two
      charged colloidal particles by computer simulations of the primitive model of
      strongly asymmetric electrolytes with an explicitly added hard-sphere solvent.
      Apart from molecular oscillating forces for nearly touching colloids that arise
      from solvent and counterion layering, the counterions are attracted towards the
      colloidal surfaces by solvent depletion providing a simple statistical
      description of hydration. This, in turn, has an important influence on the
      effective forces for larger distances which are considerably reduced as compared
      to the prediction based on the primitive model. When these forces are repulsive,
      the long-distance behavior can be described by an effective Yukawa pair potential
      with a solvent-renormalized charge. As a function of colloidal volume fraction
      and added salt concentration, this solvent-renormalized charge behaves
      qualitatively similar to that obtained via the Poisson-Boltzmann cell model, but
      there are quantitative differences. For divalent counterions and nanosized
      colloids, on the other hand, the hydration may lead to overscreened colloids with
      mutual attraction while the primitive model yields repulsive forces. All these
      new effects can be accounted for through a solvent-averaged primitive model (SPM)
      which is obtained from the full model by integrating out the solvent degrees of
      freedom. The SPM was used to access larger colloidal particles without simulating
      the solvent explicitly.

PMID- 11308840
TI  - Particle-counterion clustering in highly charge-asymmetric complex fluids.
AB  - The formation of particle-counterion clusters through electrostatic interaction
      is studied in this work for a highly charge asymmetric colloidal suspension. The
      occurrence of such clustering is probed by the particle electrophoretic mobility,
      i.e., with the aid of a transport property. The results show that the effective
      charge manifesting under the presence of an external electric field is the
      renormalized charge predicted by an extension of the Debye-Huckel-Bjerrum theory
      to the fluid state of highly charged colloids.

PMID- 11308841
TI  - Inhomogeneous model colloid-polymer mixtures: adsorption at a hard wall.
AB  - We study the equilibrium properties of inhomogeneous model colloid-polymer
      mixtures. By integrating out the degrees of freedom of the ideal polymer coils,
      we derive a formal expression for the effective one-component Hamiltonian of the
      (hard sphere) colloids that is valid for arbitrary external potentials acting on
      both the colloids and the polymers. We show how one can recover information about
      the distribution of polymer in the mixture given knowledge of the colloid
      correlation functions calculated using the effective one-component Hamiltonian.
      This result is then used to furnish the connection between the free-volume and
      perturbation theory approaches to determining the bulk phase equilibria. For the
      special case of a planar hard wall the effective Hamiltonian takes an explicit
      form, consisting of zero-, one-, and two-body, but no higher-body, contributions
      provided the size ratio q=sigma(p)/sigma(c)<0.1547, where sigma(c) and sigma(p)
      denote the diameters of colloid and polymer respectively. We employ a simple
      density functional theory to calculate colloid density profiles from this
      effective Hamiltonian for q=0.1. The resulting profiles are found to agree well
      with those from Monte Carlo simulations for the same Hamiltonian. Adding very
      small amounts of polymer gives rise to strong depletion effects at the hard wall
      which lead to pronounced enhancement of the colloid density profile (close to the
      wall) over what is found for hard spheres at a hard wall.

PMID- 11308842
TI  - Mode-coupling theory for heteropolymers.
AB  - We study the Langevin dynamics of a heteropolymer by means of a mode-coupling
      approximation scheme, giving rise to a set of coupled integro-differential
      equations relating the response and correlation functions. The analysis shows
      that there is a regime at low temperature characterized by out-of-equilibrium
      dynamics, with violation of time-translational invariance and of the fluctuation
      dissipation theorem. The onset of aging dynamics at low temperatures gives
      insight into the nature of the slow dynamics of a disordered polymer. We also
      introduce a renormalization-group treatment of our mode-coupling equations, which
      supports our analysis, and might be applicable to other systems.

PMID- 11308843
TI  - Dynamic light scattering from lyotropic lamellar phases subjected to a flow
      field.
AB  - Dynamic light scattering experiments on lyotropic lamellar phases of brine and
      surfactant subjected to a flow field have been realized. The obtained results
      reveal that the relaxation times measured depend strongly on the velocity of the
      flow. This dependence is indicative of an increase of the effective elasticity
      modulus K and a decrease of the effective compressibility modulus (-)B of the
      lamellar phase with the flow velocity. This leads to the conclusion that the
      shear can induce a suppression of the undulation fluctuations of the bilayers of
      the lamellar phase. Our results show also that the rigidity of the membranes
      decreases as the salt concentration of the sample increases.

PMID- 11308844
TI  - Cell dynamics simulations of shear-induced alignment and defect annihilation in
      stripe patterns formed by block copolymers.
AB  - The effect of large amplitude oscillatory shear on two-dimensional stripe
      patterns formed by block copolymers was investigated using cell dynamics
      simulations. A global orientational order parameter S and a correlation function
      for stripe normals G(r-r(')) were used to characterize the degree of stripe
      orientation under shear. The kinetics of stripe alignment, quantified by S, at
      various shear and quench conditions were studied as a function of strain
      amplitude, shear frequency, and temperature. The mechanisms of shear alignment
      and defect annihilation were investigated. A critical shear condition for
      complete alignment of stripes along the shear direction was also identified.

PMID- 11308845
TI  - Performances of holographic gratings monitored by laser-induced phase separation
      in liquid mixtures.
AB  - We theoretically describe and experimentally explore the kinetics of holographic
      grating formation resulting from different laser-induced phase separation
      mechanisms. Our method makes use of two interfering c.w. laser waves to quench
      binary mixtures in composition, and to optically trap the nucleated domains on
      the fringes. Essentially, two different processes can lead to these variations in
      concentration: electrostriction and thermodiffusion. The former originates from
      induced dipolar couplings in a field gradient; as photopolymerization, this is a
      local process which is essentially sensitive to the q=q(0) Fourier mode forced by
      the fringe modulation. The latter corresponds to a variation in composition
      driven by a small thermal gradient; as solvent evaporation and thermal heating
      techniques, it is nonlocal and behaves as 1/q(2) because of its dissipative
      origin. By making experiments in both cases, we show that this q dependence on
      excitation has a strong influence on the performance of holographic gratings.
      While in the first case reflectivity saturates because the phase transition is
      confined by the fringes which behave as separated optical boxes with "soft walls"
      which calibrate the droplet size, blurring is expected for fringe-trapped domains
      induced by a nonlocal phase transition because the transition is governed by the
      Gaussian shape of the pump beams, and nucleated domains can reach a much larger
      size than the fringe spacing. The good agreement observed with our general model
      clearly illustrates how to make the difference between local and nonlocal
      excitations, and offers a first step towards a unified description of holographic
      grating formation monitored by phase transitions.

PMID- 11308846
TI  - Two continuous models for the dynamics of sandpile surfaces.
AB  - We consider a modified Bouchaud-Cates-Ravi Prakash-Edwards model for pile surface
      dynamics, and show that in the long-scale limit this model converges to a
      quasistationary model of pile growth in the form of an evolutionary variational
      inequality.

PMID- 11308847
TI  - Dynamic phase transitions in confined lubricant fluids under shear.
AB  - A surface force apparatus was used to measure the transient and steady-state
      friction forces between molecularly smooth mica surfaces confining thin films of
      squalane, C30H62, a saturated, branched hydrocarbon liquid. The dynamic friction
      "phase diagram" was determined under different shearing conditions, especially
      the transitions between stick-slip and smooth sliding "states" that exhibited a
      chaotic stick-slip regime. The apparently very different friction traces
      exhibited by simple spherical, linear, and branched hydrocarbon films under shear
      are shown to be due to the much longer relaxation times and characteristic length
      scales associated with transitions from rest to steady-state sliding, and vice
      versa, in the case of branched liquids. The physical reasons and tribological
      implications for the different types of transitions observed with spherical,
      linear, and branched fluids are discussed.

PMID- 11308848
TI  - Curvature effects in rapid alloy solidification.
AB  - The growth of a cylindrical or spherical crystal into its undercooled melt is a
      process whose description is complicated by the lack of a stationary regime. A
      simple approach to the problem, justified for low growth rates and widely used in
      the past for both pure substances and alloy solidification, is based on a
      quasistatic approximation which assumes an instantaneous adaptation of the
      diffusional field to the interface configuration. For alloy solidification,
      assuming isothermal conditions and local interface equilibrium, this simplified
      model predicts a diffusion controlled growth, with the radius of the crystal
      increasing asymptotically as ~t(1/2). However, as pointed out by recent
      investigations, thermal diffusion and nonequilibrium effects enter as essential
      ingredients in rapid alloy solidification. In the present paper we use the phase
      field model to simulate the cylindrical and spherical growth of a solid germ into
      a supersaturated alloy melt. The problem is treated in its full time-dependent
      characteristics, accounting for nonequilibrium effects as well as for the
      rejection of both heat and solute away from the advancing front. We observe a
      complex behavior and a rich variety of dynamic regimes: in different regions of
      parameter space the growth rate is limited by diffusion (either thermal or
      chemical) or is kinetic controlled. Traversing the boundaries which limit these
      regions, the process undergoes sharp transitions which leave a trace in the
      solidified alloy. For realistic values of the Lewis number, thermal effects drive
      the process into a a diffusive regime, in which the rate limiting mechanism is
      the rejection of solute.

PMID- 11308849
TI  - Stability of modulated-gravity-induced thermal convection in magnetic fields.
AB  - A stability analysis is presented of modulated-gravity-induced thermal convection
      in a heated fluid layer subject to an applied magnetic field. The nearest
      correction to the critical Rayleigh number for both single and multiple frequency
      oscillating-gravity components is obtained by solving the linearized
      magnetohydrodynamic equations using the small parameter perturbation technique.
      The correction depends on both the applied magnetic field and the oscillating
      frequency. In the absence of an applied magnetic field, the correction depends on
      the Prandtl number only when the exciting frequency is small. However, it
      asymptotically approaches zero as the frequency increases, with or without the
      presence of a magnetic field. The heated fluid layer is more stable with gravity
      modulation than with any type of wall temperature modulation. The difference
      becomes smaller with decreasing Prandtl number Pr. This finding is of critical
      importance in that ground-based experiments with appropriate wall temperature
      modulations may be conducted to simulate the oscillating-gravity effects on the
      onset of thermal convection in lower-Prandtl-number fluids. For conducting melts
      considered for microgravity applications, it is possible to apply an external
      magnetic field to further inhibit the onset of modulated-gravity-induced thermal
      convection. This effectiveness increases with the Hartmann number Ha. For large
      Ha, the nearest correction term R02 approximately Ha2 as the magnetic Prandtl
      number Pm<<1. However, R02 approximately Ha(4/3) for Ha>>1 and Pm>>1, provided
      that Ha<0.5pi(Pm/Pr(3/2)), which is satisfied by a majority of space melt
      experiments. Thus, under normal laboratory conditions applied magnetic fields are
      more effective in stabilizing a conducting fluid subject to an oscillating
      gravity field than one subject to a constant field. If Ha>0.5pi(Pm/Pr(3/2)), R02
      approximately -Ha2 for Ha>>1 and Pm>>1 and the magnetic field becomes less
      effective in stabilizing thermal convection driven by oscillating gravity than
      that driven by the constant gravity. This is in contrast with the existing
      studies on thermal convection stability in a magnetic field, which show that
      marginal stability is independent of Pm and always increases with increasing
      applied field.

PMID- 11308850
TI  - Brillouin scattering study of molten zinc chloride.
AB  - Polarized and depolarized Brillouin scattering experiments on molten ZnCl2 were
      performed between 300 and 600 degrees C in different geometries. VV spectra
      measured in backscattering and small angle scattering were analyzed with
      conventional viscoelastic theory using either a Debye or a Cole-Davidson model
      for the memory function. We also analyzed in the same way the temperature
      dependence of the transverse Brillouin lines detected in a 90 degrees VH
      geometry. We show that the Cole-Davidson memory function yields a consistent
      interpretation of all the spectra. The resulting shear and longitudinal
      relaxation times are equal within their error bars, and are about 2.5 times
      smaller than the alpha relaxation time previously determined. The static shear
      viscosity values deduced from the analysis of the propagating transverse waves
      agree, at all temperatures, with the measured viscosity values.

PMID- 11308851
TI  - Response function of a sphere in a viscoelastic two-fluid medium.
AB  - In order to address basic questions of importance to microrheology, we study the
      dynamics of a rigid sphere embedded in a model viscoelastic medium consisting of
      an elastic network permeated by a viscous fluid. We calculate the complete
      response of a single bead in this medium to an external force, and compare the
      result to the commonly-accepted, generalized Stokes-Einstein relation (GSER). We
      find that our response function is well approximated by the GSER only within a
      particular frequency range determined by the material parameters of both the bead
      and the network. We then discuss the relevance of this result to recent
      experiments. Finally we discuss the approximations made in our solution of the
      response function by comparing our results to the exact solution for the response
      function of a bead in a viscous (Newtonian) fluid.

PMID- 11308852
TI  - Realistic calculation of the low- and high-density liquid phase separation in a
      charged colloidal dispersion.
AB  - A realistic statistical-mechanics model is applied to describe the repulsive
      interaction between charged colloids. The latter, in combination with the long
      range van der Waals attraction simulated under excess salt environment, gives
      rise to a total intercolloidal particle potential showing a clear second
      potential minimum. Differing from the usual Derjaguin-Landau-Verwey-Overbeek
      (DLVO) model, the present model is valid at any finite concentration of colloids
      and is thus an appropriate model for investigating the low- and high-density
      liquid phase transition. Employing this two-body colloid-colloid potential and in
      conjunction with the Weeks-Chandler-Andersen [J. D. Weeks, D. Chandler, and H. C.
      Andersen, J. Chem. Phys. 54, 5237 (1971)] thermodynamic perturbation theory, we
      derive analytical expressions for the pressure, chemical potential, and related
      thermodynamic functions. These thermodynamic quantities were used to calculate
      the phase diagrams of charged colloidal dispersions in terms of the critical
      parameters: temperature, volume fraction, and electrolyte concentration parameter
      k(D). Compared with the DLVO model, we find the areas enclosed within the
      spinodal decomposition and also the liquid-liquid coexistence curves broader in
      the present model for an excess salt condition kappa=k(D)sigma(0)< or similar to
      200, sigma(0) being the macroion diameter, in addition to exhibiting a shift in
      the critical point kappa(c) to lower values; for kappa>300, the disparities
      between the two models reduce. The same thermodynamic perturbation theory has
      been employed to study also the weak reversible coagulation whose physical origin
      is attributed to the presence of the second potential minimum. We examine various
      colloidal parameters that affect the structure of the latter and deduce from our
      analysis the conditions of colloidal stability. In comparison with the measured
      flocculation data for a binary mixture of polystyrene lattices and water, we find
      that our calculated results are generally reasonable, thus lending great credence
      to the presently used model.

PMID- 11308853
TI  - Magnetic-field-induced anisotropic curvature elasticity of a vesicle membrane
      containing magnetic polyions.
AB  - Interaction between a charged membrane and the electrolyte solution containing
      magnetic polyions is considered. A self-magnetic field, which arises due to the
      nonhomogeneous magnetic particle distribution near a charged membrane increases
      the effective charge screening length for the parts of a membrane normal to a
      magnetic field. The anisotropy of elastic properties of a membrane depending on
      the screening length is calculated on the basis of the curvature expansion. It is
      shown that due to diminishing of the spontaneous curvature for the parts of a
      membrane normal to a magnetic field there are two competing mechanisms of the
      ferrovesicle shape transformation under the influence of a magnetic field-the
      formation of a prolate shape orientated along a field due to the diminishing
      action of the demagnetizing field energy and the deformation to a oblate shape
      due to the decrease in the spontaneous curvature of the parts of a membrane
      normal to a field.

PMID- 11308854
TI  - Surface-directed spinodal decomposition in binary fluid mixtures.
AB  - We consider the phase separation of binary fluids in contact with a surface,
      which is preferentially wetted by one of the components of the mixture. We review
      the results available for this problem and present numerical results obtained
      using a mesoscopic level simulation technique for the three-dimensional problem.

PMID- 11308855
TI  - Flow through percolation clusters: NMR velocity mapping and numerical simulation
      study.
AB  - Three- and (quasi-)two-dimensional percolation objects have been fabricated based
      on Monte Carlo generated templates. The object size was up to 12 cm (300 lattice
      sites) in each dimension. Random site, semicontinuous swiss-cheese, and
      semicontinuous inverse swiss-cheese percolation models above the percolation
      threshold were considered. The water-filled pore space was investigated by
      nuclear magnetic resonance (NMR) imaging and, after exerting a pressure gradient,
      by NMR velocity mapping. The spatial resolutions of the fabrication process and
      the NMR experiments were 400 microm and better than 300 microm, respectively. The
      experimental velocity resolution was 60 microm/s. The fractal dimension, the
      correlation length, and the percolation probability can be evaluated both from
      the computer generated templates and the corresponding NMR spin density maps.
      Based on velocity maps, the percolation backbones were determined. The fractal
      dimension of the backbones turned out to be smaller than that of the complete
      cluster. As a further relation of interest, the volume-averaged velocity was
      calculated as a function of the probe volume radius. In a certain scaling window,
      the resulting dependence can be represented by a power law, the exponent of which
      was not yet considered in the theoretical literature. The experimental results
      favorably compare to computer simulations based on the finite-element method
      (FEM) or the finite-volume method (FVM). This demonstrates that NMR microimaging
      as well as FEM/FVM simulations reliably reflect transport features in percolation
      clusters.

PMID- 11308856
TI  - Kinetic roughening model with opposite Kardar-Parisi-Zhang nonlinearities.
AB  - We introduce a model that simulates a kinetic roughening process with two kinds
      of particle: one follows ballistic deposition (BD) kinetics and the other
      restricted solid-on-solid Kim-Kosterlitz (KK) kinetics. Both of these kinetics
      are in the universality class of the nonlinear Kardar-Parisi-Zhang equation, but
      the BD kinetics has a positive nonlinear constant while the KK kinetics has a
      negative one. In our model, called the BD-KK model, we assign the probabilities p
      and (1-p) to the KK and BD kinetics, respectively. For a specific value of p, the
      system behaves as a quasilinear model and the up-down symmetry is restored. We
      show that nonlinearities of odd order are relevant in this low nonlinear limit.

PMID- 11308859
TI  - Adsorbed layer structure of cationic surfactants on quartz.
AB  - Recent atomic force microscopy (AFM) surface images of surfactant adsorbed at
      solid and solution interfaces have shown apparent micellar aggregates familiar
      from bulk self-assembly. This contradicts the classical picture of laterally
      unstructured bilayers within which neutron reflectometry (NR) measurements have
      previously been analyzed. Applying both techniques to surfactant adsorption on
      quartz, we show that film thickness and coverage parameters derived from NR
      results are generally consistent with those from AFM and bulk self-assembly. NR
      by itself allows us to distinguish between actual bilayer and probable aggregate
      adsorption, which will be of particular importance when a solution's rheology
      makes AFM imaging impractical.

PMID- 11308857
TI  - Monte Carlo studies of model Langmuir monolayers.
AB  - This paper examines some of the basic properties of a model Langmuir monolayer,
      consisting of surfactant molecules deposited onto a water subphase. The
      surfactants are modeled as rigid rods composed of a head and tail segment of
      diameters sigma(hh) and sigma(tt), respectively. The tails consist of n(t)
      approximately 4-7 effective monomers representing methylene groups. These rigid
      rods interact via site-site Lennard-Jones potentials with different interaction
      parameters for the tail-tail, head-tail, and head-head interactions. In a
      previous paper, we studied the ground-state properties of this system using a
      Landau approach. In the present paper, Monte Carlo simulations were performed in
      the canonical ensemble to elucidate the finite-temperature behavior of this
      system. Simulation techniques, incorporating a system of dynamic filters, allow
      us to decrease CPU time with negligible statistical error. This paper focuses on
      several of the key parameters, such as density, head-tail diameter mismatch, and
      chain length, responsible for driving transitions from uniformly tilted to
      untilted phases and between different tilt-ordered phases. Upon varying the
      density of the system, with sigma(hh)=sigma(tt), we observe a transition from a
      tilted (NNN)-condensed phase to an untilted-liquid phase and, upon comparison
      with recent experiments with fatty acid-alcohol and fatty acid-ester mixtures [M.
      C. Shih, M. K. Durbin, A. Malik, P. Zschack, and P. Dutta, J. Chem. Phys. 101,
      9132 (1994); E. Teer, C. M. Knobler, C. Lautz, S. Wurlitzer, J. Kildae, and T. M.
      Fischer, J. Chem. Phys. 106, 1913 (1997)], we identify this as the L'(2)/Ov-L1
      phase boundary. By varying the head-tail diameter ratio, we observe a decrease in
      T(c) with increasing mismatch. However, as the chain length was increased we
      observed that the transition temperatures increased and differences in T(c) due
      to head-tail diameter mismatch were diminished. In most of the present research,
      the water was treated as a hard surface, whereby the surfactants are only allowed
      to move within the plane of this surface. However, we have also utilized a more
      realistic model for the surfactant-water interactions, developed by Karaborni and
      Toxvaerd, in order to examine the role which the coupled effects of head group
      size and head group-subphase interactions plays in determining tilt ordering and
      on the stability of the monolayer. It is found that increasing the head diameter
      results in a widening of the air-water interface and an associated destruction of
      orientational order. Furthermore, the onset of capillary waves at lower
      temperatures for larger head diameters implies that the L2-L1 phase boundary for
      acids and acetates should move to lower temperatures relative to the L'(2)/Ov-L1
      phase boundary for alcohols and esters. This feature has yet to be seen in
      experimental studies.

PMID- 11308858
TI  - Epitaxial growth with elastic interaction: submonolayer island formation.
AB  - A model for island formation in submonolayer epitaxy has been studied in the
      presence of elastic strain by means of a Monte Carlo simulation. The description,
      based on rate equations, leads to scaling predictions for cluster statistics and
      diffusion rates. We generalize these predictions to include the effects of the
      repulsive elastic interaction. The elastic interaction is caused by the
      deformation of the underlying substrate and has a repulsive 1/r(3) character. To
      enable the efficient simulation of multiparticle surface diffusion with long
      range interaction, we employ a multigrid scheme. One particular result is that,
      with increasing elastic repulsion between the adsorbed particles, the formation
      of islands is hampered, and island nucleation is deferred to higher coverage
      values.

PMID- 11308860
TI  - Casimir force in a critical film formed from an electrolytic solution.
AB  - We have studied the thickness of vapor adsorbed films of the critical binary
      liquid mixture acetic acid plus nonane adsorbed onto a silicon wafer substrate as
      a function of temperature near the critical temperature. This critical film
      possesses opposite boundary conditions (+-) at its two surfaces and, due to the
      dissociation of acetic acid, both the electrostatic force and the dispersion
      force affect the adsorbed film thickness. On approaching the critical temperature
      T(c), an increase in the film thickness L is observed, implying that the sign of
      the universal Casimir amplitude Delta(+-) is positive, consistent with
      theoretical predictions. However, we find quantitative discrepancies in the value
      of Delta(+-) and the form of the critical Casimir pressure scaling function
      vartheta(+-) compared with previous experimental results. We attribute these
      discrepancies to the complex nature of the critical system studied in this
      experiment.

PMID- 11308861
TI  - Computer simulation of topological defects around a colloidal particle or droplet
      dispersed in a nematic host.
AB  - We use molecular dynamics to study the ordering of a nematic liquid crystal
      around a spherical particle or droplet. Homeotropic boundary conditions and
      strong anchoring create a hedgehog (radial point defect) director configuration
      on the particle surface and in its vicinity; this topological defect is canceled
      by nearby defect structures in the surrounding liquid crystal, so as to give a
      uniform director field at large distances. We observe three defect structures for
      different particle sizes: a quadrupolar one with a ring defect surrounding the
      particle in the equatorial plane; a dipolar one with a satellite defect at the
      north or south pole; and a transitional, nonequatorial, ring defect. These
      observations are broadly consistent with the predictions of the simplest elastic
      theory. By studying density and order-parameter maps, we are able to examine
      behavior near the particle surface, and in the disclination core region, where
      the elastic theory is inapplicable. Despite the relatively small scale of the
      inhomogeneities in our systems, the simple theory gives reasonably accurate
      predictions of the variation of defect position with particle size.

PMID- 11308862
TI  - Optical studies of the liquid crystal B2 phase formed by banana-shaped molecules.
AB  - Null-transmission ellipsometry and depolarized light microscopy have been
      performed on free-standing films of three achiral banana-shaped compounds in the
      B2 phase. Our results support a two-layer unit cell previously proposed to
      explain the observed antiferroelectricity in thin films and bulk samples. We have
      studied thicker films than previously reported and have found no deviations in
      the film structure from the earlier findings. Moreover, we can determine the
      layer spacing, the molecular tilt from the layer normal, and the three principal
      indices of refraction in the molecular reference frame.

PMID- 11308863
TI  - Effect of a rigid nonpolar solute on the splay, bend elastic constants, and on
      rotational viscosity coefficient of 4,4'-n-octyl-cyanobiphenyl.
AB  - The effect of a rigid nonpolar nonmesogenic solute "biphenyl," that is, C6H5-C6H5
      on the splay and bend elastic constants and on the rotational viscosity
      coefficient of 4,4'-n-octyl-cyanobiphenyl is reported. The experiments involve
      the measurement of the voltage dependence of the capacitance of a cell filled
      with the mixture. Anomalous behavior of both K11 and Deltaepsilon near the N-S(A)
      transition have been observed.

PMID- 11308864
TI  - X-ray reflectivity study of smectic wetting and prewetting at the free surface of
      isotropic liquid crystals.
AB  - We study the structures of free-surface-wetting layers above the isotropic to
      smectic-A transition of three liquid-crystal compounds that show different kinds
      of growth of the wetting film as the bulk transition is approached: layer-by
      layer, continuous, and continuous with prewetting. The smectic-A surface phase of
      the layer-by-layer compound consists of well-defined layers and possesses a sharp
      boundary to the isotropic bulk phase, whereas in the two continuous compounds
      sinusoidal density oscillations with a continuously decaying amplitude are found.
      In the continuous case with prewetting, the wetting film below the prewetting
      transition does not show an essential difference to the continuous case without
      prewetting.

PMID- 11308865
TI  - Optical generation of inversion walls in nematic liquid crystals.
AB  - An approach to generate inversion walls in nematic liquid crystals using optical
      reorientation is described. Planar cells with small pretilt are exposed to an
      oblique laser beam, which reverses the director tilt angle within the irradiated
      area. During the electric Freedericksz transition an inversion wall surrounding
      the laser spot is formed. A theoretical relation is provided for the critical
      laser intensity necessary to produce an inversion wall. Experimental results in a
      dye-doped nematic are in satisfactory agreement with the theory.

PMID- 11308866
TI  - Molecular-dynamics study of the nematic-isotropic interface.
AB  - We present large-scale molecular-dynamics simulations of a nematic-isotropic
      interface in a system of repulsive ellipsoidal molecules, focusing in particular
      on the capillary-wave fluctuations of the interfacial position. The interface
      anchors the nematic phase in a planar way, i.e., the director aligns parallel to
      the interface. Capillary waves in the direction parallel and perpendicular to the
      director are considered separately. We find that the spectrum is anisotropic, the
      amplitudes of capillary waves being larger in the direction perpendicular to the
      director. In the long-wavelength limit, however, the spectrum becomes isotropic
      and compares well with the predictions of a simple capillary-wave theory.

PMID- 11308867
TI  - Arising of magnetic walls in the vicinities of the Freedericksz transition.
AB  - In this paper, the dynamical formation of twist-bend periodic walls at the
      neighborhoods of the Freedericksz critical point of a nematic sample of liquid
      crystals is studied. The theory that describes the arising of these periodic
      structures affirms that the mode with the fastest initial growth will fix the
      observed properties of these patterns. But, just above the Freedericksz threshold
      there is a region where this leading mode becomes null and, therefore, a
      homogeneous bending of the director may be detected. This prediction was not
      confirmed by the experiment, and walls with very well defined wavelength were
      found. We will show here that the fastest growing mode cannot be defined around
      the Freedericksz threshold and, therefore, a new way to compute the observed
      periodicity must be formulated. We assume that the observed wall results from a
      sum of a continuum and nonsharp distribution of modes in which the null mode is
      at the center.

PMID- 11308868
TI  - Zipping and collapse of diblock copolymers.
AB  - Using exact enumeration methods and Monte Carlo simulations, we study the phase
      diagram relative to the conformational transitions of a diblock copolymer in two
      dimensions. The polymer is made of two homogeneous strands of monomers of
      different species which are joined to each other at one end. We find that,
      depending on the values of the energy parameters in the model, there is either a
      first order collapse from a swollen phase to a compact phase of spiral type, or a
      continuous transition to an intermediate zipped phase followed by a first order
      collapse at lower temperatures. Critical exponents of the zipping transition are
      computed, and their exact values are conjectured on the basis of a mapping onto
      percolation geometry, thanks to recent results on path-crossing probabilities.

PMID- 11308869
TI  - Theory for phase transitions in diblock copolymers: the lamellar case.
AB  - A mean-field type theory is proposed to study order-disorder transitions (ODT's)
      in block copolymers. The theory applies to both the weak segregation and the
      strong segregation regimes. An energy functional is proposed without appealing to
      the random phase approximation (RPA). We find additional terms unaccounted for
      within the RPA. We work out in detail transitions to the lamellar state and
      compare the method to other existing theories of the ODT and numerical
      simulations. We find good agreement with recent experimental results and predict
      that the intermediate segregation regime may have more than one scaling behavior.

PMID- 11308870
TI  - Polymer depletion interaction between two parallel repulsive walls.
AB  - The depletion interaction between two parallel repulsive walls confining a dilute
      solution of long and flexible polymer chains is studied by field-theoretic
      methods. Special attention is paid to self-avoidance between chain monomers
      relevant for polymers in a good solvent. Our direct approach avoids the mapping
      of the actual polymer chains on effective hard or soft spheres. We compare our
      results with recent Monte Carlo simulations [A. Milchev and K. Binder, Eur. Phys.
      J. B 3, 477 (1998)] and with experimental results for the depletion interaction
      between a spherical colloidal particle and a planar wall in a dilute solution of
      nonionic polymers [D. Rudhardt, C. Bechinger, and P. Leiderer, Phys. Rev. Lett.
      81, 1330 (1998)].

PMID- 11308871
TI  - Macroscopic dynamics in separable neural networks.
AB  - Parallel dynamics of neural networks with separable coupling is given starting
      from Coolen-Sherrington theory. Away from saturation, it is shown that this
      parallel retrieve dynamics is equivalent to the sequential dynamics for finite
      temperature. But the finite-size effects were found to be governed by a
      homogeneous Markov process, not by a time-dependent Ornstein-Uhlenbeck process in
      sequential dynamics.

PMID- 11308872
TI  - Statistical analysis of the fractal gating motions of the enzyme
      acetylcholinesterase.
AB  - The enzyme acetylcholinesterase has an active site that is accessible only by a
      "gorge" or main channel from the surface, and perhaps by secondary channels such
      as the "back door." Molecular-dynamics simulations show that these channels are
      too narrow most of the time to admit substrate or other small molecules. Binding
      of substrates is therefore "gated" by structural fluctuations of the enzyme.
      Here, we analyze the fluctuations of these possible channels, as observed in the
      10.8-ns trajectory of the simulation. The probability density function of the
      gorge proper radius (defined in the text) was calculated. A double-peak feature
      of the function was discovered and therefore two states with a threshold were
      identified. The relaxation (transition probability) functions of these two states
      were also calculated. The results revealed a power-law decay trend and an
      oscillation around it, which show properties of fractal dynamics with a "complex
      exponent." The cross correlation of potential energy versus proper radius was
      also investigated. We discuss possible physical models behind the fractal protein
      dynamics; the dynamic hierarchical model for glassy systems is evaluated in
      detail.

PMID- 11308873
TI  - Dramatic rigidification of a peptide-decorated lamellar phase.
AB  - We have performed small-angle x-ray scattering on a lamellar (L(alpha)) phase
      made of a nonionic surfactant (C12E4), decane, and water, after the insertion of
      a triblock peptide. The hydrophilic part of the peptide is rigid and organized in
      an alpha helix in the presence of membranes. Surface tension measurements and
      spectrofluorometry show that the peptide lies on the membrane surface. The Caille
      parameter eta and the smectic compressibility modulus (-)B decrease with peptide
      concentration, whereas the membrane bending rigidity kappa increases threefold
      for mole ratio of peptide to surfactant as low as 5.2 x 10(-4). The published
      models for rigid inclusions in membranes cannot account for this dramatic
      rigidification. However, experimental results are well fitted by a Heuristic
      renormalization of the membrane thickness.

PMID- 11308874
TI  - Influence of an external electric field on cAMP wave patterns in aggregating
      Dictyostelium discoideum.
AB  - Effects of an external electric field on the propagation of excitable cyclic
      adenosin monophosphate (cAMP) pulses in aggregating cells of Dictyostelium
      discoideum have been studied by means of numerical simulations. The mathematical
      model includes a three-variable version of the Martiel-Goldbeter kinetic model of
      cAMP production by cells, and diffusion and electromigration of cAMP through
      intercellular space. Electric field effects on the planar pulses propagating in a
      spatially one-dimensional system and on circular and spiral pulses propagating in
      a spatially two-dimensional system include changes in the propagation velocities
      of pulses initiated in the field-free system, the annihilation of pulses
      propagating towards the cathode by electric fields of high intensities, and the
      formation of region(s) of spontaneous excitation permanently generating trains of
      cAMP pulses. The spiral patterns were found to drift in the electric fields of
      low intensities, fields of high intensities were found to decompose the spiral
      arms on the side facing the negative electrode.

PMID- 11308875
TI  - Mutual information in a dilute, asymmetric neural network model.
AB  - Neural networks with asymmetric synaptic connections (w(ij) not equal to w(ji))
      display a broad range of dynamical behavior including fixed point, periodic, and
      "chaotic" trajectories. Previous work has shown that such networks undergo an
      order-chaos phase transition as various network parameters, such as the
      connectivity or the degree of asymmetry, are changed. Here, using an information
      theoretic approach, we present results which suggest that neurons are able to
      communicate information to each other most effectively in networks that are near
      the order-chaos transition. We then extend the model to incorporate some
      biologically relevant features.

PMID- 11308876
TI  - Motion of phospholipidic vesicles along an inclined plane: sliding and rolling.
AB  - The migration of giant phospholipidic vesicles along an inclined plane in a
      quiescent fluid was observed as a function of the mass and the radius R of the
      vesicles, and as a function of the angle of inclination of the plane. Vesicles
      were swollen, and did not adhere to the substrate surface. It was observed from a
      side-view chamber that they have quasispherical shapes. The vesicles mainly slide
      along the plane, but also roll. The ratio omegaR/v of rotational to translational
      velocities is of the order of 0.15 for vesicles of radius ranging from 10 to 30
      microm. Values of this ratio, and variations of v versus R, are well described by
      Goldman et al.'s model developed for the motion of rigid spheres close to a wall
      [Chem. Eng. Sci. 22, 637 (1967)]. In this framework, the thickness of the fluid
      film between the vesicle and the substrate derived from fitting experimental data
      was found to be equal to 48 nm.

PMID- 11308877
TI  - Periodically forced leaky integrate-and-fire model.
AB  - The discharge pattern of periodically forced leaky integrate-and-fire models is
      studied. While previous analyses have been mainly concerned with the response of
      this model to sinusoidal stimulation, our results hold for arbitrary periodic
      inputs. It is shown that, for any periodic input, the map representing the
      relation between input phases at consecutive discharge times can be restricted to
      a piecewise continuous, orientation preserving circle map. This implies that (i)
      the rotation number is well defined and independent of the initial condition, and
      (ii) in the same way as for sinusoidal forcing, other forms of periodic stimuli
      can evoke only one of four types of response, namely, phase locking,
      quasiperiodic discharges, nonchaotic aperiodic firing, and termination of the
      discharge after a finite number of firings.

PMID- 11308878
TI  - Evolution in a spatially structured population subject to rare epidemics.
AB  - We study a model that gives rise to spatially inhomogeneous population densities
      in a system of host individuals subject to rare, randomly distributed disease
      events. For stationary hosts that disperse offspring over short distances,
      evolutionary dynamics can lead to persistent populations with a variety of
      spatial structures. A mean-field analysis is shown to account for the behavior
      observed in simulations of a one-dimensional system, where the evolutionarily
      stable state corresponds to the solution of a straightforward optimization
      problem. In two dimensions, evolution drives the system to a stable critical
      state that is less well understood.

PMID- 11308879
TI  - Modal analysis of corticothalamic dynamics, electroencephalographic spectra, and
      evoked potentials.
AB  - The effects of cortical boundary conditions and resulting modal aspects of
      continuum corticothalamic electrodynamics are explored, including feedbacks.
      Dispersion relations, electroencephalographic spectra, and stimulus response
      functions are calculated from the underlying physiology, and the effects of
      discrete mode structure are determined. Conditions under which modal effects are
      important are obtained, along with estimates of the point at which modal series
      can be truncated, and the limit in which only a single globally uniform mode need
      be retained. It is found that for physiologically plausible parameters only the
      lowest cortical spatial eigenmode together with the set of next-lowest modes can
      produce distinct modal structure in spectra and response functions, and then only
      at frequencies where corticothalamic resonances reduce dissipation to the point
      where the spatial eigenmodes are weakly damped. The continuum limit is found to
      be a good approximation, except at very low frequencies and, under some
      circumstances, near the alpha resonance. It is argued that the major
      electroencephalographic rhythms result from corticothalamic feedback resonances,
      but that cortical modal effects can contribute to weak substructure in the alpha
      resonance. This mechanism is compared and contrasted with purely cortical and
      pacemaker-based alternatives and testable predictions are formulated to enable
      experimental discrimination between these possibilities.

PMID- 11308880
TI  - Membrane curvature induced by polymer adsorption.
AB  - The phenomena resulting from interaction between polymers and membranes pose
      important problems for biological applications. Based on a scaling theory, we
      investigate the spontaneous curvature of a membrane induced by either flexible or
      semiflexible chain adsorption. Irrespective of chain stiffness, a weakly adsorbed
      polymer induces the membrane to bend away (to have a positive curvature) from the
      polymer mostly due to increase of the conformational entropy compared with that
      for a flat surface. On the other hand, a strongly adsorbed polymer induces the
      membrane to bend toward the polymer mostly due to decrease in the interaction
      energy, leading to a possibility of encapsulation of polymer by the membrane.

PMID- 11308882
TI  - Spiral waves in excitable media with negative restitution.
AB  - We study numerically the dynamics of spiral waves in an excitable medium with
      negative restitution. For our study we use two models of the excitable medium: a
      cellular automaton and a reaction-diffusion model. There are no significant
      effects of negative restitution as long as the slope of the restitution curve is
      less steep than -1. In media with slopes steeper than -1, the dynamics of spiral
      waves can change significantly: (1) the average restitution time jumps to a value
      where the slope of the restitution curve is about -1; (2) spiral waves can break
      up into turbulent patterns. We discuss a possible connection between such
      instabilities and fibrillation in atrial tissue.

PMID- 11308883
TI  - Using DNA to construct and power a nanoactuator.
AB  - A DNA-based molecular machine is described which has two movable arms that are
      pushed apart when a strand of DNA, the fuel strand, hybridizes with a single
      stranded region of the molecular machine. Through the process of branch
      migration, a second strand of DNA complementary to the fuel strand is able to
      remove the fuel strand from the molecular machine, restoring it to its original
      configuration. Compared with the molecular tweezers we had previously devised,
      this machine, which we call a nanoactuator, has a reduced tendency to form
      dimers.

PMID- 11308881
TI  - Competition model for aperiodic stochastic resonance in a Fitzhugh-Nagumo model
      of cardiac sensory neurons.
AB  - Regional cardiac control depends upon feedback of the status of the heart from
      afferent neurons responding to chemical and mechanical stimuli as transduced by
      an array of sensory neurites. Emerging experimental evidence shows that neural
      control in the heart may be partially exerted using subthreshold inputs that are
      amplified by noisy mechanical fluctuations. This amplification is known as
      aperiodic stochastic resonance (ASR). Neural control in the noisy, subthreshold
      regime is difficult to see since there is a near absence of any correlation
      between input and the output, the latter being the average firing (spiking) rate
      of the neuron. This lack of correlation is unresolved by traditional energy
      models of ASR since these models are unsuitable for identifying "cause and
      effect" between such inputs and outputs. In this paper, the "competition between
      averages" model is used to determine what portion of a noisy, subthreshold input
      is responsible, on average, for the output of sensory neurons as represented by
      the Fitzhugh-Nagumo equations. A physiologically relevant conclusion of this
      analysis is that a nearly constant amount of input is responsible for a spike, on
      average, and this amount is approximately independent of the firing rate. Hence,
      correlation measures are generally reduced as the firing rate is lowered even
      though neural control under this model is actually unaffected.

PMID- 11308884
TI  - Histogram method to obtain heat capacities in lipid monolayers, curved bilayers,
      and membranes containing peptides.
AB  - Lipid monolayer chain melting transitions were simulated using a two-state
      Doniach model, and experimental melting profiles of lipid vesicles were analyzed.
      We sampled the information of a Monte Carlo simulation into a single broad
      histogram containing complete information about the distribution of states. The
      information of the monolayer histogram was first used to calculate the melting
      behavior of a bilayer constructed from two uncoupled monolayers. We then fitted
      calorimetric heat profiles of various preparations of dipalmitoyl
      phosphatidylcholine vesicles. This analysis was extended to lipid bilayers. A
      fixed mean bilayer curvature was shown to result in a broadening of bilayer
      melting profiles. We furthermore used the histogram method to obtain the chain
      melting behavior of simple lipid-peptide mixtures.

PMID- 11308885
TI  - Critical dynamics of the Baxter-Wu model.
AB  - The short-time behavior of the Baxter-Wu model is investigated through the
      relaxation of the order parameter at the critical temperature. We considered
      Monte Carlo simulations for this model on a triangular lattice, and we studied
      relaxation starting from the fourfold-degenerate ground state. Using the short
      time scaling formalism we found the static critical exponents beta and nu of the
      model and the corresponding dynamical critical exponent z. The values of the
      static exponents we find agree with the exact ones. To the best of our knowledge,
      this is the first determination of the dynamical critical exponent of the Baxter
      Wu model.

PMID- 11308886
TI  - Phase transition in an asymmetric generalization of the zero-temperature Glauber
      model.
AB  - An asymmetric generalization of the zero-temperature Glauber model on a lattice
      is introduced. The dynamics of the particle-density and especially the large-time
      behavior of the system is studied. It is shown that the system exhibits two kinds
      of phase transitions, a static one and a dynamic one.

PMID- 11308887
TI  - Relative entropy: free energy associated with equilibrium fluctuations and
      nonequilibrium deviations.
AB  - Using a one-dimensional macromolecule in aqueous solution as an illustration, we
      demonstrate that the relative entropy from information theory, Sigma(k)p(k)
      ln(p(k)/p(*)(k)), has a natural role in the energetics of equilibrium and
      nonequilibrium conformational fluctuations of the single molecule. It is
      identified as the free energy difference associated with a fluctuating density in
      equilibrium, and is associated with the distribution deviate from the equilibrium
      in nonequilibrium relaxation. This result can be generalized to any other
      isothermal macromolecular system using the mathematical theories of large
      deviations and Markov processes, and at the same time provides the well-known
      mathematical results with interesting physical interpretations.

PMID- 11308888
TI  - Global equation of state of two-dimensional hard sphere systems.
AB  - Hard sphere systems in two dimensions are examined for arbitrary density.
      Simulation results are compared to the theoretical predictions for both the low-
      and the high-density limit, where the system is either disordered or ordered,
      respectively. The pressure in the system increases with the density, except for
      an intermediate range of volume fractions 0.65< or =nu< or =0.75, where a
      disorder-order phase transition occurs. The proposed global equation of state
      (which describes the pressure for all densities) is applied to the situation of
      an extremely dense hard sphere gas in a gravitational field and shows reasonable
      agreement with both experimental and numerical data.

PMID- 11308889
TI  - Long-range effects in granular avalanching.
AB  - We introduce a model for granular flow in a one-dimensional rice pile that
      incorporates rolling effects through a long-range rolling probability for the
      individual rice grains proportional to r(-rho), r being the distance traveled by
      a grain in a single toppling event. The exponent rho controls the average rolling
      distance. We have shown that the crossover from the power law to the stretched
      exponential behaviors observed experimentally in the granular dynamics of rice
      piles can be well described as a long-range effect resulting from a change in the
      transport properties of individual grains. We showed that stretched exponential
      avalanche distributions can be associated with a long-range regime for 1<rho<2,
      where the average rolling distance grows as a power law with the system size,
      while power law distributions are associated with a short-range regime for rho>2,
      where the average rolling distance is independent of the system size.

PMID- 11308890
TI  - Three-dimensional rotational Langevin dynamics and the Lebwohl-Lasher model.
AB  - We introduce a new scheme for molecular-dynamics simulation of three-dimensional
      systems exhibiting rotational motions. The procedure is based on the Langevin
      dynamics method. Our paper is focused on the Lebwohl-Lasher model in order to
      simulate the isotropic-nematic transition of liquid crystals. In contrast to
      previous dynamic approximations, our approach allows one to reproduce well the
      isotropic phase of these systems.

PMID- 11308891
TI  - Experimental evidence for a torus breakdown in a glow discharge plasma.
AB  - A global bifurcation scenario for a two-frequency torus breakdown depicted by
      Baptista and Caldas [Physica D 132, 325 (1999)] is observed on a glow-discharge
      experiment. The torus is broken through a crisis with an unstable periodic orbit.
      The torus section before the bifurcation is a sided polygon that has a number of
      edges equal to the period of the unstable orbit. Since the discharge is an
      extended system the two-frequency torus breakdown is shown to be a possible way
      to space-time chaos.

PMID- 11308892
TI  - Comment on "Two-finger selection theory in the Saffman-Taylor problem".
AB  - It is pointed out that the two-parameter family of solutions for the Saffman
      Taylor problem recently studied by Magdaleno and Casademunt [Phys. Rev. E 60,
      R5013 (1999)] does not correspond to two fingers moving in a Hele-Shaw cell with
      the channel geometry, as was implied in their paper. It is thus clarified that
      their solution, while correctly describing a periodic array of axisymmetric
      fingers in an unbounded Hele-Shaw cell, gives rather a central finger flanked by
      two half-fingers when restricted to a channel with impermeable rectilinear walls.
      The correct four-parameter family of exact solutions for two unequal fingers in
      such a channel is presented for the zero surface tension case.

PMID- 11308894
TI  - Dynamics of efficiency: a simple model.
AB  - We propose a simple model that describes the dynamics of efficiencies of
      competing agents. Agents communicate leading to increase of efficiencies of
      underachievers, and an efficiency of each agent can increase or decrease
      irrespectively of other agents. When the rate of deleterious changes exceeds a
      certain threshold, the system falls into a stagnant phase. In the opposite
      situation, the average efficiency improves with asymptotically constant rate and
      the efficiency distribution has a finite width. The leading algebraic corrections
      to the asymptotic growth rate are also computed.

PMID- 11308895
TI  - Fast Monte Carlo algorithm for supercooled soft spheres.
AB  - We present a nonlocal Monte Carlo algorithm with particle swaps that greatly
      accelerates thermalization of soft sphere binary mixtures in the glassy region.
      Our first results show that thermalization of systems of hundreds of particles is
      achievable, and find behavior compatible with a thermodynamic glass transition.

PMID- 11308896
TI  - Finite size scaling of domain chaos.
AB  - Numerical studies of the domain chaos state in a model of rotating Rayleigh
      Benard convection suggest that finite size effects may account for the
      discrepancy between experimentally measured values of the correlation length and
      the predicted divergence near onset.

PMID- 11308897
TI  - Attractor bifurcation and on-off intermittency.
AB  - We analyze the bifurcation of an attractor in a system of multiplicatively
      coupled maps. It is shown that the phenomenon can be characterized by on-off
      intermittency and it is rigorously described by the on-off intermittency in the
      presence of noise through the concept of a virtually invariant manifold.
      Presenting numerical results which conform our claims, we elucidate the role of
      on-off intermittency in bifurcation phenomena.

PMID- 11308898
TI  - Spectral correlations: understanding oscillatory contributions.
AB  - We give a different derivation of a relation obtained using a supersymmetric
      nonlinear sigma model by Andreev and Altshuler [Phys. Rev. Lett. 72, 902 (1995)],
      which connects smooth and oscillatory components of spectral correlation
      functions. We show that their result is not specific to the random matrix theory.
      Also, we show that despite an apparent contradiction, the results obtained using
      their formula are consistent with earlier perspectives on random matrix models.

PMID- 11308899
TI  - Flow pattern dynamics in convecting liquid helium.
AB  - We present experimental data which correlate thermal measurements and flow
      visualization in convecting liquid 4He. For a small range R(C)<R<R1 of the
      Rayleigh number R above the convection threshold value R(C) a robust stationary
      pattern is observed. This pattern exhibits periodic pulsation when R>R1,
      generating thermal oscillations as in earlier reports. At higher R values the
      time dependence becomes aperiodic with the surprising appearance of spiral-defect
      chaos at an aspect ratio smaller than has previously been reported.

PMID- 11308900
TI  - Scaling laws in two-dimensional turbulent convection.
AB  - Two-dimensional homogeneous turbulent convection is studied numerically. Though
      Bolgiano-Obukhov scaling is approximately valid, strong differences exist in the
      intermittency properties of velocity and temperature increments, where the latter
      are similar to those of a passive scalar. The main difference of the small-scale
      dynamics compared to a passive scalar arises from the Kelvin-Helmholtz
      instability, but this process does not affect the scaling properties. A condition
      for a scalar field to show the ramp-and-cliff structures of a passive scalar is
      discussed.

PMID- 11308901
TI  - Observation of the 1/2 power law in Rayleigh-Benard convection.
AB  - The 1/2 power law is reported in a Rayleigh-Benard experiment: Nu approximately
      Ra(1/2), where Ra and Nu are the Rayleigh and Nusselt numbers. This observation
      is coherent with the predictions of the ultimate convection regime, characterized
      by fully turbulent heat transfers. Ordered rough boundaries are used to cancel
      the correction due to the thickness variation of the viscous sublayer, and the
      observation of the asymptotic regime is therefore possible. This result supports
      the interpretation of a laminar-turbulent boundary-layer transition to account
      for the observation of Chavanne et al. of a new regime [X. Chavanne et al., Phys.
      Rev. Lett. 79, 3648 (1997)].

PMID- 11308902
TI  - Critical wavelength for river meandering.
AB  - A fully nonlinear modal analysis identifies a critical centerline wave number
      q(c) for river meandering that separates long-wavelength bends, which grow to
      cutoff, from short-wavelength bends, which decay. Exact, numerical, and
      approximate analytical results for q(c) rely on the Ikeda, Parker, and Sawai [J.
      Fluid Mech. 112, 363 (1981)] model, supplemented by dynamical equations that
      govern the river migration and length. Predictions also include upvalley bend
      migration at long times and a peak in lateral migration rates at intermediate
      times. Experimental tests are suggested.

PMID- 11308903
TI  - Bridge from diffusion-limited aggregation to the Saffman-Taylor problem.
AB  - We introduce a Monte Carlo mean-field scheme for the diffusion-limited
      aggregation (DLA) model, in order to simulate processes of viscous fingering. The
      patterns obtained demonstrate a striking resemblance to natural shapes in Hele
      Shaw cells, reproducing the Saffman-Taylor analytical solutions in the stable
      regime. The corresponding deterministic equations of the mean-field DLA scheme
      are derived and studied.

PMID- 11308904
TI  - Dynamics of the charging and motion of a macroparticle in a plasma flow.
AB  - The dynamics of motion and charging of a macroscopic "dust" particle in a plasma
      with an ion flow is investigated by employing the particle-in-cell method. It is
      demonstrated that the charging and motion of the dust particle levitating in an
      external parabolic potential is related to the ion flow. This situation is
      relevant for the majority of experiments on the self-organization and
      crystallization of colloidal dust grains in a low-temperature plasma.

PMID- 11308905
TI  - Type of inversion problem in physics: an inverse emissivity problem.
AB  - Inversion problems have recently drawn vast amounts of attention from the physics
      community due to their potential widespread applications. In this Rapid
      Communication, a different type of inversion problem in physics is proposed: an
      inverse emissivity problem, which aims to determine the emissivity g(nu) by
      measuring only the total radiated power J(T). Like other inverse problems, this
      one has potential for important practical applications. An exact solution is
      obtained for the proposed inverse problem. A unique existence theorem and
      techniques for eliminating divergences are also presented. A universal function
      set (UFS) suggested for numerical calculations is shown to be very useful in a
      numerical example. The UFS makes this inversion method practical and convenient
      for realistic calculations.

PMID- 11308906
TI  - Renormalization-group theoretical reduction.
AB  - It has been known for some time that singular perturbation and reductive
      perturbation can be unified from the renormalization-group (RG) theoretical point
      of view. However, renormalization-group approaches to singularly perturbed
      problems require explicit perturbation results, so they could be complicated
      practically. The approach proposed in this paper has considerably eliminated the
      need for explicit perturbation results, making the RG approach simpler than many
      conventional singular perturbation approaches. Consequently, we may assert that
      reductive extraction of global features of the problem is the essence of singular
      perturbation methods.

PMID- 11308907
TI  - Pseudospectral approach to inverse problems in interface dynamics.
AB  - An improved scheme for computing coupling parameters of the Kardar-Parisi-Zhang
      equation from a collection of successive interface profiles is presented. The
      approach hinges on a spectral representation of this equation. An appropriate
      discretization based on a Fourier representation is discussed as a by-product of
      the above scheme. Our method is first tested on profiles generated by a one
      dimensional Kardar-Parisi-Zhang equation, where it is shown to reproduce the
      input parameters very accurately. When applied to microscopic models of growth,
      it provides the values of the coupling parameters associated with the
      corresponding continuum equations. This technique compares favorably with
      previous methods based on real space schemes.

PMID- 11308908
TI  - Yang-Lee circle theorem for an ideal pseudospin-1/2 Bose gas in an external
      magnetic field.
AB  - The Yang-Lee circle theorem is extended to an ideal pseudospin-1/2 Bose gas in an
      external magnetic field. It is found that the zeros of the canonical partition
      function are located on the unit circle in the complex activity plane if the
      temperature is above the critical temperature of ideal Bose-Einstein
      condensation. No zeros exist if the temperature is below the critical
      temperature.

PMID- 11308909
TI  - Modeling of locally self-similar processes using multifractional Brownian motion
      of Riemann-Liouville type.
AB  - Fractional Brownian motion (FBM) is widely used in the modeling of phenomena with
      power spectral density of power-law type. However, FBM has its limitation since
      it can only describe phenomena with monofractal structure or a uniform degree of
      irregularity characterized by the constant Holder exponent. For more realistic
      modeling, it is necessary to take into consideration the local variation of
      irregularity, with the Holder exponent allowed to vary with time (or space). One
      way to achieve such a generalization is to extend the standard FBM to
      multifractional Brownian motion (MBM) indexed by a Holder exponent that is a
      function of time. This paper proposes an alternative generalization to MBM based
      on the FBM defined by the Riemann-Liouville type of fractional integral. The
      local properties of the Riemann-Liouville MBM (RLMBM) are studied and they are
      found to be similar to that of the standard MBM. A numerical scheme to simulate
      the locally self-similar sample paths of the RLMBM for various types of time
      varying Holder exponents is given. The local scaling exponents are estimated
      based on the local growth of the variance and the wavelet scalogram methods.
      Finally, an example of the possible applications of RLMBM in the modeling of
      multifractal time series is illustrated.

PMID- 11308910
TI  - Information theory based on nonadditive information content.
AB  - We generalize Shannon's information theory in a nonadditive way by focusing on
      the source coding theorem. The nonadditive information content we adopted is
      consistent with the concept of the form invariance structure of the nonextensive
      entropy. Some general properties of the nonadditive information entropy are
      studied, in addition, the relation between the nonadditivity q and the codeword
      length is pointed out.

PMID- 11308911
TI  - Phase transitions of hard disks in external periodic potentials: a Monte Carlo
      study.
AB  - The nature of freezing and melting transitions for a system of hard disks in a
      spatially periodic external potential is studied using extensive Monte Carlo
      simulations. Detailed finite size scaling analysis of various thermodynamic
      quantities like the order parameter, its cumulants, etc., are used to map the
      phase diagram of the system for various values of the density and the amplitude
      of the external potential. We find clear indication of a reentrant liquid phase
      over a significant region of the parameter space. Our simulations therefore show
      that the system of hard disks behaves in a fashion similar to charge-stabilized
      colloids that are known to undergo an initial freezing, followed by a remelting
      transition as the amplitude of the imposed, modulating field produced by crossed
      laser beams is steadily increased. Detailed analysis of our data shows several
      features consistent with a recent dislocation unbinding theory of laser induced
      melting.

PMID- 11308912
TI  - Anomalous behavior of the contact process with aging.
AB  - The effect of power-law aging on a contact process is studied by simulation and
      using a mean-field approach. The introduced type of aging accounts for, e.g., the
      growth of the virus fitness (HIV infection). We find that the system may approach
      its stationary state in a nontrivial, nonmonotonous way. For the particular value
      of the aging exponent alpha=1 we observe a rich set of behaviors: depending on
      the process parameters, the relaxation to the stationary state proceeds as 1/ln t
      or via a power law with a nonuniversal exponent. Simulation results suggest that
      for 0<alpha<1, the absorbing-state phase transition is in the universality class
      of directed percolation.

PMID- 11308913
TI  - Kinetic roughening with anisotropic growth rules.
AB  - Inspired by the chemical etching processes, where experiments show that growth
      rates depending on the local environment might play a fundamental role in
      determining the properties of the etched surfaces, we study here a model for
      kinetic roughening that includes explicitly an anisotropic effect in the growth
      rules. Our model introduces a dependence of the growth rules on the local
      environment conditions, i.e., on the local curvature of the surface. Variables
      with different local curvatures of the surface, in fact, present different
      quenched disorder and a parameter p (which could represent different experimental
      conditions) is introduced to account for different time scales for the different
      classes of variables. We show that the introduction of this time scale separation
      in the model leads to a crossover effect on the roughness properties. This effect
      could explain the scattering in the experimental measurements available in the
      literature. The interplay between anisotropy and the crossover effect and the
      dependence of critical properties on parameter p is investigated as well as the
      relationship with the known universality classes.

PMID- 11308914
TI  - Phase transition of a quasi-one-dimensional system.
AB  - The statistical mechanics of the quasi-one-dimensional system of DNA is studied
      with the Morse and Deng-Fan potentials for the interstrand hydrogen bonds of
      nucleotide pairs. The intrastrand interactions between nucleotides are
      characterized by a simple harmonic potential in which the coupling strength has a
      significant effect on the phase transition of the DNA system.

PMID- 11308915
TI  - Friction in a solid lubricant film.
AB  - Molecular-dynamics study of a thin (one to five layers) lubricant film between
      two substrates in moving contact are performed using Langevin equations with an
      external damping coefficient depending on distance and velocity of atoms relative
      the substrates, motivated by microscopic configurations. They show that the
      minimal friction coefficient is obtained for the solid-sliding regime. A detailed
      analysis of the results, the comparison with other microscopic modeling
      approaches of friction, and the evaluation of quantities that can be compared to
      experiments, such as the velocity of the transition from stick slip to smooth
      sliding, are used to discuss the relevance of the microscopic simulations of
      friction.

PMID- 11308916
TI  - Exact density profiles for the fully asymmetric exclusion process with discrete
      time dynamics on semi-infinite chains.
AB  - Exact density profiles in the steady state of the one-dimensional fully
      asymmetric simple-exclusion process on a semi-infinite chain are obtained in the
      case of forward-ordered sequential dynamics by taking the thermodynamic limit in
      our recent exact results for a finite chain with open boundaries. The
      corresponding results for sublattice-parallel dynamics follow from the
      relationship obtained by Rajewsky and Schreckenberg [Physica A 245, 139 (1997)],
      and for parallel dynamics from the mapping found by Evans, Rajewsky, and Speer
      [J. Stat. Phys. 95, 45 (1999)]. Our analytical expressions involve Laplace-type
      integrals, rather than complicated combinatorial expressions, which makes them
      convenient for taking the limit of a semi-infinite chain, and for deriving the
      asymptotic behavior of the density profiles at large distances from its end. By
      comparing the asymptotic results appropriate for parallel update with those
      published in the above cited paper by Evans, Rajewsky, and Speer, we find
      complete agreement except in two cases, in which we correct technical errors in
      the final results given there.

PMID- 11308917
TI  - Scaling in steady-state aggregation with injection.
AB  - A mean-field approach for steady-state aggregation with injection is presented.
      It is shown that for a wide variety of aggregation processes the resulting steady
      size distribution obeys a power law N(m) approximately m(-alpha) with
      alpha=(3+beta)/2 and beta the degree of homogeneity of the coagulation kernel.
      The general conditions for this to happen are obtained. Some applications are
      studied. In particular, it predicts a potential behavior for coagulation in
      atmospheric aerosols with exponent alpha approximately 2, in agreement with
      observations. The theoretical results also agree with some animal group-size
      distributions and with numerical simulations in fractal aggregates.

PMID- 11308918
TI  - Rigidity transition in two-dimensional random fiber networks.
AB  - Rigidity percolation is analyzed in two-dimensional random fibrous networks. The
      model consists of central forces between the adjacent crossing points of the
      fibers. Two strategies are used to incorporate rigidity: adding extra constraints
      between second-nearest crossing points with a probability p(sn), and "welding"
      individual crossing points by adding there four additional constraints with a
      probability p(weld), and thus fixing the angles between the fibers. These
      additional constraints will make the model rigid at a critical probability
      p(sn)=p(sn)(c) and p(weld)=p(weld)(c), respectively. Accurate estimates are given
      for the transition thresholds and for some of the associated critical exponents.
      The transition is found in both cases to be in the same universality class as
      that of the two-dimensional central-force rigidity percolation in diluted
      lattices.

PMID- 11308919
TI  - Application of the quantum spin glass theory to image restoration.
AB  - Quantum fluctuation is introduced into the Markov random-field model for image
      restoration in the context of a Bayesian approach. We investigate the dependence
      of the quantum fluctuation on the quality of a black and white image restoration
      by making use of statistical mechanics. We find that the maximum posterior
      marginal (MPM) estimate based on the quantum fluctuation gives a fine restoration
      in comparison with the maximum a posteriori estimate or the thermal fluctuation
      based MPM estimate.

PMID- 11308920
TI  - Kinetics of domain growth in systems with local barriers.
AB  - We study domain growth in spin-1 lattice models having nonconserved spin-flip
      kinetics with local barriers. Our primary motivation is to model the relaxational
      behavior of physical systems in which molecular motion is impeded by local
      kinetic barriers. The kinetic constraint is such that a spin from an up (down)
      state can flip to a down (up) state only via the zero state, which has a higher
      energy. We examine how the usual curvature-driven domain growth is affected by
      these local barriers, and whether the single-spin barriers have a collective
      effect. This paper presents comprehensive numerical results for phase ordering
      dynamics in this model using Monte Carlo simulations. We demonstrate dynamical
      scaling for domain-size distribution functions and spatial correlation functions.
      We also present results for the time dependence of characteristic length scales
      and autocorrelation functions. The length-scale behavior is interpreted in terms
      of the random walk of steps on domain boundaries. Furthermore, we present a
      simple stochastic model to derive an analytic expression for the autocorrelation
      function, which exhibits a stretched-exponential behavior over an extended regime
      in agreement with our numerical simulations.

PMID- 11308921
TI  - Nature of phase transitions in a probabilistic cellular automaton with two
      absorbing states.
AB  - We present a probabilistic cellular automaton with two absorbing states, which
      can be considered a natural extension of the Domany-Kinzel model. Despite its
      simplicity, it shows a very rich phase diagram, with two second-order and one
      first-order transition lines that meet at a bicritical point. We study the phase
      transitions and the critical behavior of the model using mean field
      approximations, direct numerical simulations and field theory. The second-order
      critical curves and the kink critical dynamics are found to be in the directed
      percolation and parity conservation universality classes, respectively. The first
      order phase transition is put in evidence by examining the hysteresis cycle. We
      also study the "chaotic" phase, in which two replicas evolving with the same
      noise diverge, using mean field and numerical techniques. Finally, we show how
      the shape of the potential of the field-theoretic formulation of the problem can
      be obtained by direct numerical simulations.

PMID- 11308922
TI  - Diffusion-limited aggregation as a Markovian process: site-sticking conditions.
AB  - Cylindrical lattice diffusion-limited aggregation, with a narrow width N, is
      solved for site-sticking conditions using a Markovian matrix method (which was
      previously developed for the bond-sticking case). This matrix contains the
      probabilities that the front moves from one configuration to another at each
      growth step, calculated exactly by solving the Laplace equation and using the
      proper normalization. The method is applied for a series of approximations, which
      include only a finite number of rows near the front. The fractal dimensionality
      of the aggregate is extrapolated to a value near 1.68.

PMID- 11308923
TI  - Fractional Fokker-Planck equation, solution, and application.
AB  - Recently, Metzler et al. [Phys. Rev. Lett. 82, 3563 (1999)], introduced a
      fractional Fokker-Planck equation (FFPE) describing a subdiffusive behavior of a
      particle under the combined influence of external nonlinear force field, and a
      Boltzmann thermal heat bath. In this paper we present the solution of the FFPE in
      terms of an integral transformation. The transformation maps the solution of
      ordinary Fokker-Planck equation onto the solution of the FFPE, and is based on
      Levy's generalized central limit theorem. The meaning of the transformation is
      explained based on the known asymptotic solution of the continuous time random
      walk (CTRW). We investigate in detail (i) a force-free particle, (ii) a particle
      in a uniform field, and (iii) a particle in a harmonic field. We also find an
      exact solution of the CTRW, and compare the CTRW result with the corresponding
      solution of the FFPE. The relation between the fractional first passage time
      problem in an external nonlinear field and the corresponding integer first
      passage time is given. An example of the one-dimensional fractional first passage
      time in an external linear field is investigated in detail. The FFPE is shown to
      be compatible with the Scher-Montroll approach for dispersive transport, and thus
      is applicable in a large variety of disordered systems. The simple FFPE approach
      can be used as a practical tool for a phenomenological description of certain
      types of complicated transport phenomena.

PMID- 11308924
TI  - Application of renormalization to the dynamics of a particle in an infinite
      square-well potential driven by an external field.
AB  - We analyze by a renormalization method the dynamics of a particle in an infinite
      square-well potential driven by an external monochromatic field. This method
      setup for Hamiltonian systems with two degrees of freedom allows us to analyze
      precisely the stability of the trajectories of the particle as a function of the
      amplitude epsilon of the external field. We compute numerical values of epsilon
      for which the motion of the particle with frequency omega is broken and a
      transition to a chaotic behavior occurs. We obtain the critical function
      epsilon(c)(omega) associated with this system as a function of the parameters
      such as the frequency of the field and the width of the potential.

PMID- 11308925
TI  - Pattern selection in extended periodically forced systems: a continuum coupled
      map approach.
AB  - We propose that a useful approach to the modeling of periodically forced extended
      systems is through continuum coupled map (CCM) models. CCM models are discrete
      time, continuous space models, mapping a continuous spatially varying field
      xi(n)(x) from time n to time n+1. The efficacy of CCM models is illustrated by an
      application to experiments of Umbanhowar, Melo, and Swinney [Nature 382, 793
      (1996)] on vertically vibrated granular layers. Using a simple CCM model
      incorporating temporal period doubling and spatial patterning at a preferred
      length scale, we obtain results that bear remarkable similarities to the
      experimental observations. The fact that the model does not make use of physics
      specific to granular layers suggests that similar phenomena may be observed in
      other (nongranular) periodically forced, strongly dissipative systems. We also
      present a framework for the analysis of pattern selection in CCM models using a
      truncated modal expansion. Through the analysis, we predict scaling laws of
      various quantities, and these laws may be verifiable experimentally.

PMID- 11308926
TI  - Periodic orbits and topological entropy of delayed maps.
AB  - The periodic orbits of a nonlinear dynamical system provide valuable insight into
      the topological and metric properties of its chaotic attractors. In this paper we
      describe general properties of periodic orbits of dynamical systems with feedback
      delay. In the case of delayed maps, these properties enable us to provide general
      arguments about the boundedness of the topological entropy in the high delay
      limit. As a consequence, all the metric entropies can be shown to be bounded in
      this limit. The general considerations are illustrated in the cases of Bernoulli
      like and Henon-like delayed maps.

PMID- 11308927
TI  - Restricted feedback control of one-dimensional maps.
AB  - Dynamical control of biological systems is often restricted by the practical
      constraint of unidirectional parameter perturbations. We show that such a
      restriction introduces surprising complexity to the stability of one-dimensional
      map systems and can actually improve controllability. We present experimental
      cardiac control results that support these analyses. Finally, we develop new
      control algorithms that exploit the structure of the restricted-control stability
      zones to automatically adapt the control feedback parameter and thereby achieve
      improved robustness to noise and drifting system parameters.

PMID- 11308928
TI  - Noise-induced Brownian motion of spiral waves.
AB  - We study the erratic displacement of spiral waves forced to move in a medium with
      random spatiotemporal excitability. Analytical work and numerical simulations are
      performed in relation to a kinematic scheme, assumed to describe the autowave
      dynamics for weakly excitable systems. Under such an approach, the Brownian
      character of this motion is proved and the corresponding dispersion coefficient
      is evaluated. This quantity shows a nontrivial dependence on the temporal and
      spatial correlation parameters of the external fluctuations. In particular, a
      resonantlike behavior is neatly evidenced in terms of the noise correlation time
      for the particular situation of spatially uniform fluctuations. Actually, this
      case turns out to be, to a large extent, exactly solvable, whereas a pair of
      dispersion mechanisms are discussed qualitatively and quantitatively to explain
      the results for the more general scenario of spatiotemporal disorder.

PMID- 11308929
TI  - Chaos in small-world networks.
AB  - A nonlinear small-world network model has been presented to investigate the
      effect of nonlinear interaction and time delay on the dynamic properties of small
      world networks. Both numerical simulations and analytical analysis for networks
      with time delay and nonlinear interaction show chaotic features in the system
      response when nonlinear interaction is strong enough or the length scale is large
      enough. In addition, the small-world system may behave very differently on
      different scales. Time-delay parameter also has a very strong effect on
      properties such as the critical length and response time of small-world networks.

PMID- 11308930
TI  - Parametric evolution for a deformed cavity.
AB  - We consider a classically chaotic system that is described by a Hamiltonian
      H(Q,P;x), where (Q,P) describes a particle moving inside a cavity, and x controls
      a deformation of the boundary. The quantum eigenstates of the system are /n(x)>.
      We describe how the parametric kernel P(n/m)=/<n(x)/m(x(0))>/(2), also known as
      the local density of states, evolves as a function of deltax=x-x(0). We
      illuminate the nonunitary nature of this parametric evolution, the emergence of
      nonperturbative features, the final nonuniversal saturation, and the limitations
      of random-wave considerations. The parametric evolution is demonstrated
      numerically for two distinct representative deformation processes.

PMID- 11308931
TI  - Experimental investigation of a regime of Wigner ergodicity in microwave rough
      billiards.
AB  - We study experimentally a new regime of Wigner ergodicity [K.M. Frahm and D.L.
      Shepelyansky, Phys. Rev. Lett. 79, 1833 (1997)] in a microwave rough billiard. We
      show that in the Wigner regime, eigenstates are extended over the whole energy
      surface but have a strongly peaked nonergodic structure. The Shannon width of the
      eigenstate distributions is calculated to estimate their spreads and to find
      their departure from the ergodic distributions.

PMID- 11308932
TI  - Multiple Perron-Frobenius operators.
AB  - A cycle expansion technique for discrete sums of several PF operators, similar to
      the one used in the standard classical dynamical zeta-function formalism is
      constructed. It is shown that the corresponding expansion coefficients show an
      interesting universal behavior, which illustrates the details of the interference
      between the particular mappings entering the sum.

PMID- 11308933
TI  - Complex periodic orbits, renormalization, and scaling for quasiperiodic golden
      mean transition to chaos.
AB  - At the critical point of the golden-mean quasiperiodic transition to chaos we
      show the presence of an infinite sequence of unstable orbits in complex domain
      with periods given by the Fibonacci numbers. The Floquet eigenvalues
      (multipliers) are found to converge fast to a universal complex constant. We
      explain this result on the basis of the renormalization group approach and
      suggest using it for accurate estimates of the location of the golden-mean
      critical points in parameter space for a class of nonlinear dissipative systems
      defined analytically. As an example, we obtain data for the golden-mean critical
      point in the two-dimensional dissipative invertible map of Zaslavsky. We give a
      set of graphical illustrations for the scaling properties and emphasize that
      demonstration of self-similarity on two-dimensional diagrams of Arnold tongues
      requires the use of a properly chosen curvilinear coordinate system. We discuss a
      procedure of construction of the appropriate local coordinate system in the
      parameter plane and present the corresponding data for the circle map and
      Zaslavsky map.

PMID- 11308934
TI  - Synchronization as adjustment of information rates: detection from bivariate time
      series.
AB  - An information-theoretic approach for studying synchronization phenomena in
      experimental bivariate time series is presented. "Coarse-grained" information
      rates are introduced and their ability to indicate generalized synchronization as
      well as to establish a "direction of information flow" between coupled systems,
      i.e., to discern the driving from the driven (response) system, is demonstrated
      using numerically generated time series from unidirectionally coupled chaotic
      systems. The method introduced is then applied in a case study of
      electroencephalogram recordings of an epileptic patient. Synchronization events
      leading to seizures have been found on two levels of organization of brain
      tissues and "directions of information flow" among brain areas have been
      identified. This allows localization of the primary epileptogenic areas, also
      confirmed by magnetic resonance imaging and pasitron emission tomography scans.

PMID- 11308935
TI  - Controlling spatiotemporal chaos via phase space compression.
AB  - We present a simple and effective method for controlling spatiotemporal chaos
      (STC) via phase space compression, by compressing the evolution orbit of the
      chaotic attractor. In numerical simulations, we obtain global and local control
      in coupled map lattice (CML) systems by the same phase space compression in
      different situations, and find that the functional relationship of control
      results to control parameters in a certain region is the same as the local
      dynamics expression of the CML. According to the control equation, using
      different phase space compressions we successfully control a CML exhibiting STC
      into various desired stable states.

PMID- 11308936
TI  - Parameter-adaptive identical synchronization disclosing Lorenz chaotic masking.
AB  - A parameter-adaptive rule that globally synchronizes oscillatory Lorenz chaotic
      systems with initially different parameter values is reported. In principle, the
      adaptive rule requires access to the three state variables of the drive system
      but it has been readapted to work with the exclusive knowledge of only one
      variable, a potential message carrier. The rule is very robust and can be used to
      trace parameter modulation conveying hidden messages. The driven system is
      defined according to a drive-driven type of coupling that guarantees
      synchronization if parameters are identical. From any arbitrary initial state,
      the parameters of the driven system are dynamically adapted to reach convergence
      to the drive parameter values. At this point, synchronization mismatch or
      parameter tracing is used to unmask any potential hidden message.

PMID- 11308937
TI  - Slow switching in globally coupled oscillators: robustness and occurrence through
      delayed coupling.
AB  - The phenomenon of slow switching in populations of globally coupled oscillators
      is discussed. This characteristic collective dynamics, which was first discovered
      in a particular class of the phase oscillator model, is a result of the formation
      of a heteroclinic loop connecting a pair of clustered states of the population.
      We argue that the same behavior can arise in a wider class of oscillator models
      with the amplitude degree of freedom. We also argue how such heteroclinic loops
      arise inevitably and persist robustly in a homogeneous population of globally
      coupled oscillators. Although a heteroclinic loop might seem to arise only
      exceptionally, we find that it appears rather easily by introducing time delay
      into a population which would otherwise exhibit perfect phase synchrony. We argue
      that the appearance of the heteroclinic loop induced by the delayed coupling is
      then characterized by transcritical and saddle-node bifurcations. Slow switching
      arises when a system with a heteroclinic loop is weakly perturbed. This will be
      demonstrated with a vector model by applying weak noises. Other types of weak
      symmetry-breaking perturbations can also cause slow switching.

PMID- 11308938
TI  - Chaotic neural control.
AB  - We consider the problem of stabilizing unstable equilibria by discrete controls
      (the controls take discrete values at discrete moments of time). We prove that
      discrete control typically creates a chaotic attractor in the vicinity of an
      equilibrium. Artificial neural networks with reinforcement learning are known to
      be able to learn such a control scheme. We consider examples of such systems,
      discuss some details of implementing the reinforcement learning to controlling
      unstable equilibria, and show that the arising dynamics is characterized by
      positive Lyapunov exponents, and hence is chaotic. This chaos can be observed
      both in the controlled system and in the activity patterns of the controller.

PMID- 11308939
TI  - Effects of lateral boundaries on traveling-wave dynamics in binary fluid
      convection.
AB  - The global dynamics of traveling-wave patterns in convection in a mixture of
      ethanol in water is studied in different cell geometries: circular, rectangular,
      and stadium-shaped cells. The dynamics in these cells differ greatly, changing
      from a globally rotating state in the circular cell, to one large domain of
      locally parallel traveling waves in the rectangular cell, to a continually
      chaotic state in the stadium cell. In all three cases, the patterns can be
      described in terms of the phase of the complex order parameter. Disorder in the
      patterns is quantified in terms of topological defects in the phase field. While
      the numbers, net charge, and dynamics of defects differ greatly in the patterns
      in the three cells, the local dynamics of the defects, as measured by the defect
      defect correlation functions, are similar.

PMID- 11308940
TI  - Measurement of liquid surface properties by laser-induced surface deformation
      spectroscopy.
AB  - We developed a technique of picking up the liquid surface in a noncontact manner
      by a cw-laser radiation. The momentum change of light at the laser transmission
      through the air-liquid interface appears as the radiation pressure, which deforms
      the liquid surface into the shape determined by the balance between the Laplace
      force of the curved surface and the radiation pressure. The displacement of the
      liquid surface is inversely proportional to the surface tension, which was
      measured by an optical probe. The dynamic response of the liquid surface
      deformation was theoretically derived under the periodical modulation of the
      radiation pressure. The experimentally observed spectra were in good agreement
      with the theory giving the dynamic properties of the liquid surface. The
      technique of the laser induced surface deformation has potential as a measurement
      tool of the surface dynamic properties, such as the time-dependent surface
      tension and surface viscoelasticity.

PMID- 11308941
TI  - Temperature fluctuations in a convection cell with rough upper and lower
      surfaces.
AB  - A turbulent convection experiment is conducted in a cell with rough upper and
      lower surfaces. Temperature statistics, frequency power spectrum, and thermal
      dissipation are measured over varying Rayleigh numbers in the central region of
      the cell. The temperature histogram in the rough cell is found to have the same
      exponential shape as that in the smooth cell, but the width of the distribution
      is increased by approximately 25%. The measured power spectrum shows that
      temperature fluctuations in the rough cell are increased uniformly across the
      whole frequency range. The cutoff frequency f(c) of the power spectrum and the
      time averaged square temperature time derivative <( partial differentialT/
      partial differentialt)(2)> are used to characterize the thermal dissipation in
      turbulent convection. It is found that the normalized f(c) as well as <( partial
      differentialT/ partial differentialt)(2)> in the smooth and rough cells with
      different aspect ratios can all be superposed onto a single curve, indicating
      that the thermal dissipation in these cells is determined by the same mechanism.
      The experiment suggests that the enhanced heat transport observed in the rough
      cell is determined primarily by the local dynamics near the upper and lower
      boundaries.

PMID- 11308942
TI  - Enhancement in the dynamic response of a viscoelastic fluid flowing through a
      longitudinally vibrating tube.
AB  - We analyzed the effects of elasticity on the dynamics of fluids in porous media
      by studying the flow of a Maxwell fluid in a tube, which oscillates
      longitudinally and is subject to an oscillatory pressure gradient. The present
      study investigates novelties brought about in the classic Biot theory of
      propagation of elastic waves in a fluid-saturated porous solid by inclusion of
      non-Newtonian effects that are important, for example, for hydrocarbons. Using
      the time Fourier transform and transforming the problem into the frequency
      domain, we calculated (a) the dynamic permeability, and (b) the function F(kappa)
      that measures the deviation from Poiseuille flow friction as a function of
      frequency parameter kappa. This provides a more complete theory of the flow of
      Maxwell fluid through a longitudinally oscillating cylindrical tube with an
      oscillating pressure gradient, which has important practical applications. This
      study clearly shows the transition from a dissipative regime to an elastic regime
      in which sharp enhancements (resonances) of the flow are found.

PMID- 11308943
TI  - Strange behavior of a passive scalar in a linear velocity field.
AB  - Damping (or growth) rates of a typical realization, mean-field and high-order
      correlation functions of a passive scalar (e.g., a number density of particles)
      advected by a linear velocity fields are estimated. It is shown that all
      statistical moments higher than the first moment and a typical realization of a
      passive scalar without an external pumping decay for both laminar and random
      incompressible linear velocity fields. Strong compressibility of a laminar linear
      velocity field can result in a growth of a typical realization and the high-order
      moments of a passive scalar. It is demonstrated that for a laminar compressible
      linear velocity field the flux of particles from the infinity does not vanish and
      the total number of particles is not conserved. For a random compressible linear
      velocity field a typical realization decays whereas the high-order moments of a
      passive scalar can grow. Comparison of the obtained results with those for
      dynamics of a passive scalar advected by a homogeneous isotropic and compressible
      turbulent flow with a given longitudinal two-point correlation function F=1-r(2)
      is performed (where r is the distance between two points measured in the units of
      the maximum scale of turbulent motions).

PMID- 11308944
TI  - Discreteness and quasiresonances in weak turbulence of capillary waves.
AB  - A numerical study is presented which deals with the kinematics of quasiresonant
      energy transfer in a system of capillary waves with a discrete wave number space
      in a periodic box. For a given set of initially excited modes and a given level
      of resonance broadening, the modes of the system are partitioned into two
      classes, one active, the other forbidden. For very weak nonlinearity the active
      modes are very sparse. It is possible that this sparsity explains discrepancies
      between the values of the Kolmogorov constant measured in numerical simulations
      of weakly turbulent cascades and the theoretical values obtained from the
      continuum theory. There is a critical level of nonlinearity below which the set
      of active modes has finite radius in wave number space. In this regime, an energy
      cascade to dissipative scales may not be possible and the usual Kolmogorov
      spectrum predicted by the continuum theory not realized.

PMID- 11308945
TI  - Evolution of turbulent spots in a parallel shear flow.
AB  - The evolution of turbulent spots in a parallel shear flow is studied by means of
      full three-dimensional numerical simulations. The flow is bounded by free
      surfaces and driven by a volume force. Three regions in the spanwise spot cross
      section can be identified: a turbulent interior, an interface layer with
      prominent streamwise streaks and vortices, and a laminar exterior region with a
      large scale flow induced by the presence of the spot. The lift-up of streamwise
      streaks that is caused by non-normal amplification is clearly detected in the
      region adjacent to the spot interface. The spot can be characterized by an
      exponentially decaying front that moves with a speed different from that of the
      cross-stream outflow or the spanwise phase velocity of the streamwise roll
      pattern. Growth of the spots seems to be intimately connected to the large scale
      outside flow, for a turbulent ribbon extending across the box in the downstream
      direction does not show the large scale flow and does not grow. Quantitatively,
      the large scale flow induces a linear instability in the neighborhood of the
      spot, but the associated front velocity is too small to explain the spot
      spreading.

PMID- 11308946
TI  - Spatially correlated temperature fluctuations in turbulent convection.
AB  - By measuring the degree of spatial correlation in temperature fluctuations at two
      points separated by a distance perpendicular to the mean flow, we are able to
      determine the viscous boundary layer thickness in turbulent convection. We
      demonstrate this method using water as the working fluid and find excellent
      agreement with directly measured results. Furthermore, from the most probable
      delay time for a thermal disturbance to successively pass the two temperature
      probes, we deduce the width of the mixing zone and again find very good agreement
      between the value obtained and that predicted by theory.

PMID- 11308947
TI  - Coalescence of liquid drops by surface tension.
AB  - The merging of two mercury drops at very low kinetic energy is observed using
      fast, digital, and analog imaging techniques. Sequences showing the time
      evolution of the overall-surface shape as well as an amplified view of the
      contact region are shown. Qualitative and quantitative comparisons with
      computations of the Navier-Stokes equation with a free surface are made. In the
      model, the surface is tracked by a marker-chain method.

PMID- 11308948
TI  - Chaoslike behavior in nonchaotic systems at finite computation precision.
AB  - The dynamical behavior of a two-dimensional map is investigated numerically. A
      chaoslike behavior, i.e., a nonsmooth distribution of the attractor and seemly
      sensitive dependence of the motion on initial condition is found as the system
      state is nonchaotic (both Lyapunov exponents are nonpositive). The key point for
      this strange behavior is that the mode corresponding to the second negative
      Lyapunov exponent contains positive local Lyapunov exponent segments. It is
      argued that this kind of behavior may be typical and easily observed in practical
      numerical computations and experiments where small noise is inevitable.

PMID- 11308949
TI  - Rarefaction shock wave: formation under short pulse laser ablation of solids.
AB  - We investigate formation, dynamics, and decay of the rarefaction shock wave under
      the conditions of ultrashort pulse laser ablation of solids. On the basis of the
      Euler equation and the van der Waals equation, we consider the planar and
      spherical expansion into vacuum matter heated instantaneously above the
      thermodynamic critical temperature. When the expansion occurs along an abnormal
      adiabat, in a part of which ( partial differential(2)p/ partial
      differentialv(2))/(S)<0, a rarefaction shock wave moving toward the target is
      formed. After its reflection from the nonvaporized material of the target, a thin
      dense layer of the expanding material is found to be formed. We suggest that this
      is the explanation for interference patterns observed experimentally above laser
      ablated surfaces. It has been speculated that the rarefaction shock wave may be
      formed on nova outbursts.

PMID- 11308950
TI  - Energy loss of a charged particle in a magnetized quantum plasma.
AB  - This paper investigates the stopping power of a weakly coupled magnetized plasma.
      The effect of the Larmor rotation of the heavy charged test particle is carefully
      analyzed. The dielectric formalism is employed to obtain a general expression for
      the stopping power. A quantum mechanical form of the random-phase approximation
      dielectric function is used so that an arbitrary cutoff procedure is not
      required. Simple analytical expressions for the stopping power have been found
      for the cases of high and low projectile velocity of the test particle. The
      dependence of the stopping power on the angle of incidence is studied. A
      comparison with numerical solutions is given. It is found that in general a
      magnetic field reduces the stopping power of the plasma at high velocities, while
      it increases the stopping power at low velocities.

PMID- 11308951
TI  - Effect of an internal rotating current on low-frequency inductively coupled
      plasmas.
AB  - The effect of an internal low-frequency rotating current on inductively coupled
      plasmas in cylindrical chambers is studied. The electromagnetic field structure,
      power density distribution, the plasma density, and the operating regimes of the
      discharge are investigated using electrodynamic, power, and particle balance
      equations. It is shown that the rotating current sheet can dramatically improve
      the uniformity of the electromagnetic fields and the power transferred to the
      plasma electrons from that of conventional low-frequency inductively coupled
      plasma sources with external flat spiral inductive coils.

PMID- 11308952
TI  - Vortex solitons: mass, energy, and angular momentum bunching in relativistic
      electron-positron plasmas.
AB  - It is shown that the interaction of large amplitude electromagnetic waves with a
      hot electron-positron (e-p) plasma (a principal constituent of the universe in
      the MeV epoch) leads to a bunching of mass, energy, and angular momentum in
      stable, long-lived structures. Electromagnetism in the MeV epoch, then, could
      provide a possible route for seeding the observed large-scale structure of the
      universe.

PMID- 11308953
TI  - Relaxation of the electron energy distribution function in the afterglow of a N2
      microwave discharge including space-charge field effects.
AB  - The relaxation of the electron energy distribution function (EEDF) in the post
      discharge of an omega/(2pi)=2.45 GHz microwave discharge in N2 has been
      investigated by solving the time-dependent Boltzmann equation, including a term
      taking into account electron losses by diffusion under the presence of a space
      charge field. It is shown that although the high-energy tail of the EEDF is
      rapidly depleted in times of 10(-7) s (p=2 and 10 Torr), the electron density
      n(e)(t), the electron transport parameters, and the rate coefficients for some
      processes induced by electron impact, with energy thresholds typically smaller
      than approximately 2-3 eV, such as, e.g., stepwise excitation of N2(B (3)Pi(g))
      and N2(C (3)Pi(u)) states from N2(A (3)Sigma(+)(u)) metastables and excitation of
      N2(X (1)Sigma(+)(g),v) levels, are only slowly modified in the time interval t
      approximately 10(-7)-3 x 10(-4) s due to the large characteristic times for
      ambipolar diffusion. As a result of modifications in n(e)(t), the change from
      ambipolar to free diffusion regimes occurs abruptly at t approximately 3 x 10(-4)
      and approximately 10(-3) s for p=2 and 10 Torr, respectively.

PMID- 11308954
TI  - Nonadiabatic phenomena during magnetic trap confinement and their influence on
      maximum x-ray energy from electron-cyclotron-resonance-heated plasmas.
AB  - Nonadiabatic effects during the confinement of energetic electrons with a
      gyroradius comparable with the magnetic field scale have been studied with a
      phase section technique. The appearance of a hot electron component is a
      characteristic feature of electron-cyclotron-resonance-heated plasma production
      in magnetic mirrors. A criterion for the absence of stable trajectories and the
      transition to strong stochastic motion for any initial condition is proposed and
      confirmed by simulations. Satisfactory agreement with the experimental x-ray
      spectra is obtained.

PMID- 11308955
TI  - Effect of nonadiabaticity of dust charge variation on dust acoustic waves:
      generation of dust acoustic shock waves.
AB  - The effect of nonadiabaticity of dust charge variation arising due to small
      nonzero values of tau(ch)/tau(d) has been studied where tau(ch) and tau(d) are
      the dust charging and dust hydrodynamical time scales on the nonlinear
      propagation of dust acoustic waves. Analytical investigation shows that the
      propagation of a small amplitude wave is governed by a Korteweg-de Vries (KdV)
      Burger equation. Notwithstanding the soliton decay, the "soliton mass" is
      conserved, but the dissipative term leads to the development of a noise tail.
      Nonadiabaticity generated dissipative effect causes the generation of a dust
      acoustic shock wave having oscillatory behavior on the downstream side. Numerical
      investigations reveal that the propagation of a large amplitude dust acoustic
      shock wave with dust density enhancement may occur only for Mach numbers lying
      between a minimum and a maximum value whose dependence on the dusty plasma
      parameters is presented.

PMID- 11308956
TI  - Dielectronic recombination in plasmas. II. Initial excited states.
AB  - Ions in a plasma recombine with electrons by both direct and resonant modes. The
      latter, the dielectronic recombination, can be a dominant process at temperature
      near T approximately equal to Z2 Ry, for ions with charge Z. The rates are
      usually given for target ions in their ground states, and contributions from all
      doubly excited intermediate states and final singly excited states of the
      recombined ions are summed over. To facilitate applications of the rates in
      plasma modelling in terms of rate equations, simple rate formulas are often
      devised. However, at finite temperature, a sizable fraction of ions is initially
      in an excited state, and after recombination, ions are usually left in singly
      excited final states. Thus new empirical rate formulas are needed that exhibit an
      explicit dependence on final as well as initial states of the ions before and
      after the recombination. We have calculated properly adjusted rates where (a) the
      target ions are allowed to be in their ground and excited states, and (b)
      contributions to the individual final states are explicitly separated. Multiple
      cascades are important in such calculations. For Al3+ ions we show that rates for
      the initial excited states are much larger than that for the ground state.

PMID- 11308957
TI  - Magnetic field energy dissipation due to particle trapping in a force-free
      configuration of collisionless pair plasmas.
AB  - It is shown by using a two-dimensional, fully relativistic, electromagnetic
      particle-in-cell simulation code that a force-free magnetic configuration in
      collisionless, electron-positron (pair) plasmas becomes unstable against current
      driven Buneman instability and subsequently there occurs a strong magnetic field
      energy dissipation associated with collisionless magnetic reconnection, which can
      be driven by particle trapping due to two-dimensional electric potentials
      remaining in the nonlinear stage of the initial current-driven Buneman
      instability. About 43% of the initial magnetic field energy dissipates and is
      transformed to plasma heating as well as high-energy particle production. The
      energy spectrum in the high-energy region is given by an exponential type with
      two temperatures. We also show the simulation results for the electron-ion plasma
      to compare the effect of the mass ratio of the electron and proton.

PMID- 11308958
TI  - Analysis of broadband x-ray spectra of highly charged krypton from a
      microcalorimeter detector of an electron-beam ion trap.
AB  - Spectra of highly charged Kr ions, produced in an electron-beam ion trap (EBIT),
      have been recorded in a broad x-ray energy band (0.3 keV to 4 keV) with a
      microcalorimeter detector. Most of the spectral lines have been identified as
      transitions of B- to Al-like Kr. The transition energies have been determined
      with 0.2% uncertainty. A semi-empirical EBIT plasma model has been created to
      calculate a synthetic spectrum of highly charged Kr and to determine a charge
      state distribution of Kr ions inside the EBIT.

PMID- 11308959
TI  - Use of low-density foams as pressure amplifiers in equation-of-state experiments
      with laser-driven shock waves.
AB  - The applicability of foams to equation of state experiments with laser-produced
      shocks has been studied. The pressure increase due to impedance mismatch at the
      payload-foam interface was measured experimentally using sub-ns laser pulses
      smoothed with phase zone plates. Foams of density in the range 5-900 mg/cm(3) and
      of thicknesses of 50-150 microm were used. A model has been developed to study
      pressure amplification and the conditions under which the shock is stationary.
      Two-step two-material targets, allowing simultaneous measurements of the shock
      velocities in the two materials, were then used to obtain relative equation of
      state data. Pressures higher than 100 Mbar were achieved in gold.

PMID- 11308960
TI  - Alternative approach to the numerical synthesis of the dense-ion-beam focusing
      systems.
AB  - An alternative approach has been developed to the numerical synthesis of ion-beam
      focusing systems that prepare the dense laminar ion beams with the required
      profile of the ion trajectories. Conventionally an ill-posed synthesis problem
      arises in such cases, and only low-density beams with no magnetic field are
      treated. Instead, we compute both the electric and magnetic fields by considering
      two well-posed problems, the first for the equivalent potential Q and the second
      for the electric potential U. An analytical solution for Q for the specific case
      of an axial system has been found and a self-consistent method of satisfying the
      axial boundary conditions for Poisson's equation in U is described. It is shown
      that the beam can be focused while preserving its laminar structure and the
      required profile when applying various superpositions of both the electric and
      magnetic fields.

PMID- 11308961
TI  - Simulation of laser wakefield acceleration of an ultrashort electron bunch.
AB  - The dynamics of the acceleration of a short electron bunch in a strong plasma
      wave excited by a laser pulse in a plasma channel is studied both analytically
      and numerically in slab geometry. In our simulations, a fully nonlinear,
      relativistic hydrodynamic description for the plasma wave is combined with
      particle-in-cell methods for the description of the bunch. Collective self
      interactions within the bunch are fully taken into account. The existence of
      adiabatic invariants of motion is shown to have important implications for the
      final beam quality. Similar to the one-dimensional case, the natural evolution of
      the bunch is shown to lead, under proper initial conditions, to a minimum in the
      relative energy spread.

PMID- 11308962
TI  - Self-oscillations in ring Toda chains with negative friction.
AB  - We study here the different modes of self-oscillations in ring Toda chains with
      Rayleigh-type negative friction. Assuming that at small friction the shape of
      self-oscillations is close to one of the known Toda solitonlike solutions we use
      analytical methods in combination with numerical ones for study of the self
      oscillations. We calculate explicitly for a Toda chain consisting of N elements
      the N+1 different modes of self-oscillations. Among them two modes correspond to
      left and right rotations of the chain as a whole with a constant velocity Each of
      the other N-1 modes represents a combination of solitonlike oscillations and a
      rotation with a velocity depending on the mode number. Only for the mode
      corresponding to antiphase oscillations of the chain neighboring elements (such
      oscillations are possible for an even N) the constant component of the velocity
      is equal to zero.

PMID- 11308963
TI  - Higher-order transverse modes of ultrashort isodiffracting pulses.
AB  - We present a family of space-time nonseparable analytic solutions describing
      spatiotemporal dynamics of isodiffracting single-cycle and few-cycle pulses with
      Hermite-Gaussian and Laguerre-Gaussian transverse profiles. These solutions are
      space-time localized wave packets propagating in free space. The transverse field
      profile acts as a spatially dependent filter, modifying the pulse spectrum and
      removing certain frequencies. The consequences of those effects in the time
      domain are the distortions of pulse envelope and temporal wave form and the
      creation of "dark pulses" at certain transverse positions. In addition, due to
      the space-time coupling, the instantaneous transverse field pattern changes
      inside the pulse, as well as with propagation distance. These higher-order mode
      solutions can be used to analyze reflected or scattered terahertz pulses, and to
      understand the wave-form distortions of terahertz signals in applications. They
      are also capable of modeling pulsed fields of phase locking of both transverse
      and longitudinal modes in total mode-locked lasers.

PMID- 11308964
TI  - Reflection-induced spectral changes of the pulsed radiation emitted by a point
      source.
AB  - We calculate the field emitted by a pulsed point source above a planar interface.
      It is found that the observed power spectrum can differ significantly from the
      emitted spectrum. Also, the observed power spectrum depends strongly on the wave
      speeds in the two media and on the position of the observation point with respect
      to the interface and the source.

PMID- 11308965
TI  - Superluminal transmission of information through an electromagnetic metamaterial.
AB  - A passive, matched two-time-derivative Lorentz material medium is designed to
      have its equivalent permittivity and permeability smaller than their values in
      free space over a large range of frequencies. Superluminal pulse propagation in
      this medium and consequent superluminal information exchange without a violation
      in causality are demonstrated. Additional properties of this medium are developed
      including the energy in it and the force characteristics induced on it by
      electromagnetic field interactions. It is shown that the force on the medium can
      be made to be attractive or repulsive using a change in frequency or a change in
      the material characteristics. Potential applications are discussed.

PMID- 11308966
TI  - Nonlinear Schrodinger equations with mean terms in nonresonant multidimensional
      quadratic materials.
AB  - We derive the asymptotic equations governing the evolution of a quasi
      monochromatic optical pulse in a nonresonant quadratic material starting from
      Maxwell equations. Under rather general assumptions, equations of nonlinear
      Schrodinger (NLS) type with coupling to mean fields result (here called NLSM). In
      particular, if the incident pulse is polarized along one of the principal axes of
      the material, scalar NLSM equations are obtained. For a generic input, however,
      coupled vector NLSM systems result. Special reductions of these equations include
      the usual scalar and vector NLS equations. Based on results known for similar
      systems which arise in other physical contexts, we expect the behavior of the
      solutions to be characterized by a rather large variety of phenomena. In
      particular, we show that the presence of the coupling to the dc fields can have a
      dramatic effect on the dynamics of the optical pulse, and stable localized
      multidimensional pulses can arise through interaction with boundary terms
      associated to the mean fields.

PMID- 11308967
TI  - Solitonic structures in a nonlinear model with interparticle anharmonic
      interaction.
AB  - Using a special combination of relevant parameters for a model with interparticle
      anharmonic interactions, we can predict the appearance of solitonic structures.
      The most remarkable representatives of the structures found here are the so
      called drop compactons, (solitons with compact support in the shape of hard
      spheres), cusps, peak solitons (peakons), and defects. These analytic solutions
      (similar to others in their family) are obtained by considering strong
      restrictions on the possible values of their velocities. We analyze two types of
      physical boundary condition: the trivial and the so-called condensate boundary
      conditions. The total energy concentrated in each soliton pattern is also
      calculated.

PMID- 11308968
TI  - Multistable collision cycles of Manakov spatial solitons.
AB  - We show numerically, using known state-change relations, that collision cycles of
      Manakov (1+1)-dimensional spatial solitons can exhibit multistable polarization
      states.

PMID- 11308969
TI  - Surface shape resonances and surface plasmon polariton excitations in bottle
      shaped metallic gratings.
AB  - We study surface plasmon polariton excitations and surface shape resonances in a
      lossy metallic grating with bivalued cavities. The modal formalism is used to
      solve the diffraction problem for the infinite grating and the homogeneous
      problem for a single cavity in a plane surface. Both polarization modes are
      considered. We provide curves of reflected efficiency versus wavelength as well
      as near-field plots. The resonances are identified as dips in the reflected
      efficiency, which imply significant power absorptions. Results for various depths
      of the cavities and for several angles of incidence are shown, where the
      different types of resonant behavior can be appreciated. Particular attention is
      paid to the changes introduced by the finite conductivity of the metal in
      relation to the results obtained for a perfect conductor.

PMID- 11308970
TI  - Enhancement of sum frequency generation near the photonic band gap edge under the
      quasiphase matching conditions.
AB  - We analyze theoretically and study experimentally the mechanisms of enhancement
      of the sum frequency and second harmonic generation in a finite one-dimensional
      photonic band gap structure with second order nonlinearity under Bragg
      diffraction conditions. It is shown that, near the photonic band gap edge, the
      efficiency of conversion in sum frequency and second harmonic generation
      processes can be significantly enhanced if two conditions are fulfilled
      simultaneously: grating assisted phase matching, or quasiphase matching, and an
      increase of the electromagnetic field density at the fundamental frequencies near
      the photonic band edges. The role of each mechanism is discussed.

PMID- 11308971
TI  - Selective reflection spectroscopy of a resonant vapor at the interface with a
      metallic layer.
AB  - We discuss the properties of selective reflection spectroscopy at the interface
      between a resonant vapor and a complex dense medium, such as a metallic film
      layered on a dielectric substrate. We show that in the approximation of a low
      density vapor, the signal mixes up the absorptive and dispersive components of
      the "effective resonant susceptibility" of the vapor, with the mixture amount
      governed by simple laws of linear optics. Preliminary experiments performed at
      the interface between Cs vapor (D2, 852-nm line) and a silver-coated glass window
      are reported, that show qualitatively the effect of the atom-surface van der
      Waals interaction.

PMID- 11308972
TI  - Driven kinks in discrete chains: phonon damping.
AB  - Phonon radiation is shown numerically to damp the motion of a relativistically
      driven straight phi(4) soliton, even in the extremely weak discreteness limit. At
      higher discreteness, the soliton mobility is characterized by a discontinuous
      dependence on the driving force; jumps are related to phonon and breather
      radiation thresholds. Moreover, the speed of a frictionless soliton cannot be
      lowered below a certain threshold value, or else it might get trapped between two
      adjacent chain sites.

PMID- 11308973
TI  - Two-dimensional Green's function and local density of states in photonic crystals
      consisting of a finite number of cylinders of infinite length.
AB  - Using the exact theory of multipole expansions, we construct the two-dimensional
      Green's function for photonic crystals, consisting of a finite number of circular
      cylinders of infinite length. From this Green's function, we compute the local
      density of states (LDOS), showing how the photonic crystal affects the radiation
      properties of an infinite fluorescent line source embedded in it. For frequencies
      within the photonic band gap of the infinite crystal, the LDOS decreases
      exponentially inside the crystal; within the bands, we find "hot" and "cold"
      spots. Our method can be extended to three dimensions as well as to treating
      disorder and represents an important and efficient tool for the design of
      photonic crystal devices.

PMID- 11308974
TI  - Static and dynamic transport of light close to the Anderson localization
      transition.
AB  - Anderson localization of light refers to an inhibition of wave transport in
      scattering media due to the interference of multiple scattered waves. We present
      wavelength dependent midinfrared optical transport measurements in slabs of
      randomly packed germanium (Ge) micron-sized particles, using a free electron
      laser as a tunable source of pulsed radiation. Because of their high refractive
      index and low absorption, Ge and similar semiconductors are excellent systems to
      study Anderson localization of light. To characterize the samples fully, we have
      employed several complementary optical techniques: total diffuse transmission,
      total diffuse reflection, coherent transmission, and time-resolved speckle
      interferometry. In this way we obtained the scattering (l(s)) and transport (l)
      mean free paths, the absorption coefficient (alpha), the diffusion constant (D),
      and the energy transport velocity (v(e)). These measurements have been made as a
      function of midinfrared wavelength, so that the scattering cross section and
      absorption coefficients can be varied in the same samples. We found that the Ge
      samples are close (kl(s) approximately 3) to the localization transition, but
      still above it. Our measurements of l(s) and l suggest that l is renormalized due
      to interference at the proximity of the localization transition. We also found
      that the diffusion constant is significantly reduced in samples thinner than
      approximately 7l.

PMID- 11308975
TI  - Negative phase time for scattering at quantum wells: a microwave analogy
      experiment.
AB  - If a quantum mechanical particle is scattered by a potential well, the wave
      function of the particle can propagate with negative phase time. Because of the
      analogy of the Schrodinger and Helmholtz equations this phenomenon is expected to
      be observable for electromagnetic wave propagation. Experimental data for
      electromagnetic wells realized by waveguides filled with different dielectrics
      now confirm this conjecture.

PMID- 11308977
TI  - Gap function in the finite Bak-Sneppen model.
AB  - We present several analytical results on the average lifetime of supercritical
      avalanches and the long-term behavior of the gap function in the finite Bak
      Sneppen model.

PMID- 11308976
TI  - Quantum lattice-gas model for computational fluid dynamics.
AB  - Quantum-computing ideas are applied to the practical and ubiquitous problem of
      fluid dynamics simulation. Hence, this paper addresses two separate areas of
      physics: quantum mechanics and fluid dynamics (or specifically, the computational
      simulation of fluid dynamics). The quantum algorithm is called a quantum lattice
      gas. An analytical treatment of the microscopic quantum lattice-gas system is
      carried out to predict its behavior at the mesoscopic scale. At the mesoscopic
      scale, a lattice Boltzmann equation with a nonlocal collision term that depends
      on the entire system wave function, governs the dynamical system. Numerical
      results obtained from an exact simulation of a one-dimensional quantum lattice
      model are included to illustrate the formalism. A symbolic mathematical method is
      used to implement the quantum mechanical model on a conventional workstation. The
      numerical simulation indicates that classical viscous damping is not present in
      the one-dimensional quantum lattice-gas system.

PMID- 11308978
TI  - Universality of S-matrix correlations for deterministic plus random Hamiltonians.
AB  - We study S-matrix correlations for random matrix ensembles with a Hamiltonian
      H=H(0)+straight phi, in which H0 is a deterministic NxN matrix and straight phi
      belongs to a Gaussian random matrix ensemble. Using Efetov's supersymmetry
      formalism, we show that in the limit N-->infinity correlation functions of S
      matrix elements are universal on the scale of the local mean level spacing: the
      dependence of H0 enters into these correlation functions only through the average
      S matrix and the average level density. This statement applies to each of the
      three symmetry classes (unitary, orthogonal, and symplectic).

PMID- 11308979
TI  - Critical transition in the constrained traveling salesman problem.
AB  - We investigate the finite size scaling of the mean optimal tour length as a
      function of density of obstacles in a constrained variant of the traveling
      salesman problem (TSP). The computational experience pointed out a critical
      transition (at rho(c) approximately 85%) in the dependence between the excess of
      the mean optimal tour length over the Held-Karp lower bound and the density of
      obstacles.

PMID- 11308980
TI  - Power-law correlations in the southern-oscillation-index fluctuations
      characterizing El Nino.
AB  - The southern oscillation index (SOI) is a characteristic of the El Nino
      phenomenon. SOI monthly averaged data is analyzed for the time interval 1866
      2000. The tail of the cumulative distribution of the fluctuations of SOI signal
      is studied in order to characterize the amplitude scaling of the fluctuations and
      the occurrence of extreme events. Large fluctuations are more likely to occur
      than the Gaussian distribution would predict. The time scaling of fluctuations is
      studied by applying the energy spectrum and the detrended fluctuation analysis
      statistical method. Self-affine properties are found to be pertinent to the SOI
      signal and therefore suggest power-law correlations of fluctuations of the
      signal. An antipersistent type of correlations exists for a time interval ranging
      from about 4 months to about 6 years. This leads to favoring specific physical
      models for El Nino description.

PMID- 11308981
TI  - Chaotic versus random ionization.
AB  - We use Kepler maps to study the classical ionization of the hydrogen atom driven
      by electric fields; we compare the ionization rate (IR) due to chaotic motion
      (constant field amplitude) with the IR due to randomness (random field
      amplitude). We find that for weak fields the ionization due to random amplitude
      is more effective, while for strong fields the ionization due to chaos is more
      effective; so, there is a cross of such ionization curves. A physical explanation
      of this phenomenon, based on the trajectory behavior, is given.

PMID- 11308982
TI  - Quantum breaking time scaling in superdiffusive dynamics.
AB  - We show that the breaking time of quantum-classical correspondence depends on the
      type of kinetics and the dominant origin of stickiness. For sticky dynamics of
      quantum kicked rotor, when the hierarchical set of islands corresponds to the
      accelerator mode, we demonstrate by simulation that the breaking time scales as
      tau(Planck's over 2pi) approximately (1/Planck's over 2pi)(1/mu) with the
      transport exponent mu>1 that corresponds to superdiffusive dynamics [B. Sundaram
      and G. M. Zaslavsky, Phys. Rev. E 59, 7231 (1999)]. We discuss also other
      possibilities for the breaking time scaling and transition to the logarithmic one
      tau(Planck's over 2pi) approximately ln(1/Planck's over 2pi) with respect to
      Planck's over 2pi.

PMID- 11308983
TI  - Stochastic dynamics from the fractional Fokker-Planck-Kolmogorov equation: large
      scale behavior of the turbulent transport coefficient.
AB  - The formulation of the fractional Fokker-Planck-Kolmogorov (FPK) equation
      [Physica D 76, 110 (1994)] has led to important advances in the description of
      the stochastic dynamics of Hamiltonian systems. Here, the long-time behavior of
      the basic transport processes obeying the fractional FPK equation is analyzed. A
      derivation of the large-scale turbulent transport coefficient for a Hamiltonian
      system with 11 / 2 degrees of freedom is proposed in connection with the fractal
      structure of the particle chaotic trajectories. The principal transport regimes
      (i.e., a diffusion-type process, ballistic motion, subdiffusion in the limit of
      the frozen Hamiltonian, and behavior associated with self-organized criticality)
      are obtained as partial cases of the generalized transport law. A comparison with
      recent numerical and experimental studies is given.

PMID- 11308984
TI  - Regular and anomalous scaling of a randomly advected passive scalar.
AB  - Extending Kolmogorov's refined similarity hypothesis to study the inertial
      behavior <[T(x+r,t)-T(x,t)](2n)>~r(zeta(2n)) of a passive scalar T(x,t) advected
      by a rapidly changing incompressible velocity field, a random variable straight
      theta was introduced by Ching [Phys. Rev. Lett. 79, 3644 (1997)]. In this paper,
      the statistical distribution of the random variable X=straight
      theta/sqrt[<straight theta(2)>] is investigated analytically for the scaling in
      two limits, n-independent scaling zeta(2n)=zeta(2) and regular scaling
      zeta(2n)=nzeta(2), and numerically for the scaling of the Kraichnan conjecture
      zeta(2n)=1 / 2[sqrt[4ndzeta(2)+(d-zeta(2))(2)]-(d-zeta(2))]. For n-independent
      scaling zeta(2n)=zeta(2), the statistical distribution of X tends to an
      exponential distribution when zeta(2)-->0 or d-->infinity and to a Gaussian
      distribution when zeta(2)-->2 and d=2. For regular scaling zeta(2n)=nzeta(2), the
      statistical distribution of X tends to a Gaussian distribution when zeta(2)-->0
      or d-->infinity. In d=2, there seems to be a phase transition for the probability
      density function P(X) from a convex to a concave function when the value of
      zeta(2) is increased and the critical point is zeta(2)=4/3 where the random
      variable X has a uniform distribution in [-sqrt[3],sqrt[3]]. In d=3, P(X) is a
      convex function for all 0<zeta(2)<2 and tends to a constant on its support [
      sqrt[3],sqrt[3]] when zeta(2)-->2. For the scaling of the Kraichnan conjecture,
      P(X) has two peaks in d=2 for zeta(2)>1.33, but, in d=3, it has only one peak for
      all 0<zeta(2)<2 and changes very slowly with the value of X in the neighborhood
      of X=0 as zeta(2)-->2.

PMID- 11308985
TI  - Conditional statistics of temperature fluctuations in turbulent convection.
AB  - We find that the conditional statistics of temperature difference at fixed values
      of the locally averaged temperature dissipation rate in turbulent convection
      become Gaussian in the regime where the mixing dynamics is expected to be driven
      by buoyancy. Hence, intermittency of the temperature fluctuations in this
      buoyancy-driven regime can be solely attributed to the variation of the locally
      averaged temperature dissipation rate. We further obtain the functional behavior
      of these conditional temperature structure functions. This functional form
      demonstrates explicitly the failure of dimensional arguments and enhances the
      understanding of the temperature structure functions.

PMID- 11308986
TI  - Method to measure the electric field vector in an argon glow discharge using
      laser polarization spectroscopy.
AB  - A method for measurement of the direction of the electric field in a glow
      discharge is reported. This method uses the dependence of the electronic
      excitation spectrum of argon atoms on the polarization of the laser radiation. In
      this research, laser radiation was used to excite argon atoms in a plasma from
      the 4s [3 / 2](2) metastable level to Rydberg levels, and excitation spectra were
      measured using laser optogalvanic (LOG) spectroscopy. In addition, LOG spectra of
      argon atoms interacting with an electric field were calculated by solving the
      Schrodinger equation. Good agreement was found between experimental and
      theoretical LOG spectra obtained for different polarizations of the laser
      radiation.

PMID- 11308987
TI  - Population densities of hydrogenlike ions in a non-Maxwellian plasma.
AB  - In this paper we examine the effects of non-Maxwellian electron energy
      distributions on the population densities of excited atomic levels for
      hydrogenlike ions. We model the electron energy distribution function by two
      Maxwellian finite elements, one approximating the bulk distribution with
      temperature T(b) and the other the tail distribution with temperature T(t). We
      present results for various T(b)/T(t) ratios for Si XIV.

PMID- 11308988
TI  - Frustrated total reflection: the double-prism revisited.
AB  - Geometrical optics prohibits any penetration of light into an optically rarer
      medium in the case of total reflection. When sandwiching, however, the rarer
      medium between optically denser media, a transmitted beam can be observed in the
      third medium. The experiment is often realized by a double-prism arrangement [1];
      the effect is called frustrated total reflection due to the enforced
      transmission. Amazingly, the reflected and transmitted beams are shifted with
      respect to geometrical optics as conjectured by Newton [2] and experimentally
      confirmed by Goos-Hanchen 250 years later [3]. However, inconsistent results on
      the spatial shifts have been reported [4-7]. Here we report on measurements of
      the Goos-Hanchen shift in frustrated total reflection with microwaves. We found
      an unexpected influence of the beamwidth and angle of incidence on the shift. Our
      results are not in agreement with both previous experiments [6,7] and theoretical
      predictions [8-10]. The topic of frustrated total reflection is important for
      both fundamental research and applications [11-13].

PMID- 11308989
TI  - Comment on "Electromagnetic convective cells in a nonuniform dusty plasma".
AB  - Recently, Saleem and Haque [Phys. Rev. E 60, 7612 (1999)] concluded that in the
      presence of a perturbed electron current parallel to an external magnetic field,
      the dispersion relation of the electrostatic convective cell and the
      magnetostatic modes is not modified. In the present Comment, the properties of
      electromagnetic as well as electrostatic waves in a nonuniform dusty
      magnetoplasma are reexamined, to demonstrate that Eq. (13) of the paper by Saleem
      and Haque as well as their conclusions are erroneous.

PMID- 11308990
TI  - The wisdom of the body revisited: the adrenomedullary response to mild core
      hypothermia in humans.
AB  - OBJECTIVE: In the 1920s, Walter B. Cannon first described the adrenomedullary
      response to cold, using an ingenious in vivo bioassay based on a denervated heart
      preparation. Studies in humans about antecubital venous plasma concentrations of
      norepinephrine, the sympathetic neurotransmitter, and of epinephrine, the main
      adrenomedullary hormone, have suggested sympathetic nervous system activation
      without adrenomedullary activation. The present study used arterial levels of
      these catecholamines, to determine whether adrenomedullary stimulation occurs in
      response to decreased body temperature. METHODS: Eleven healthy volunteers
      underwent central intravenous infusion of warm (37 degreeC) physiological saline,
      followed by infusion of the same volume of cold (4 degreeC) saline. Brachial
      arterial and antecubital venous plasma concentrations of norepinephrine and
      epinephrine were measured by liquid chromatography with electrochemical
      detection. RESULTS: Antecubital venous concentrations of norepinephrine increased
      markedly during cold saline infusion, with smaller and statistically borderline
      increases in concentrations of epinephrine. In contrast, concurrently obtained
      arterial concentrations of both norepinephrine and epinephrine increased
      significantly. CONCLUSIONS: The results confirm Cannon's original inference that
      cold evokes adrenomedullary activation. Prior studies about antecubital venous
      levels of catecholamines did not take into account the local hemodynamic effects
      of cold, which would increase extraction of circulating catecholamines and
      underestimate the arterial epinephrine response.

PMID- 11308991
TI  - Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients
      with adrenal tumours.
AB  - OBJECTIVE: To estimate serum levels of vascular endothelial growth factor (VEGF),
      metalloproteases MMP-2 (gelatinase A), MMP-3 (stromyelisine 1) and
      metalloprotease tissue inhibitors (TIMP-2) in patients with various benign and
      malignant adrenal tumours before and after surgery, as well as to evaluate if
      there is a correlation between serum levels of these agents and tumour types.
      METHODS: Serum levels of VEGF, MMP-2, -3 and TIMP-2 were estimated in 43 patients
      with adrenal tumour at the admission and, in case of surgery, again one month
      after surgery. The patients were divided into 6 groups according to the type of
      the tumour (I - patients with adrenal cortex carcinoma, II - with benign
      hormonally active adrenocortical adenomas, III - with benign, hormonally inactive
      adenocortical adenomas (incidentaloma), IV - with benign, hormonally active
      phaeochromocytomas, V - with hormonally quiescent phaeochromocytomas, VI -
      hormonally inactive adrenal tumours of extraglandular origin. The control group
      consisted of 10 healthy individuals. RESULTS: There was no correlation between
      MMP-2 serum levels and tumour types and no significant difference between MMP-2
      level before and after surgery. There were no significant differences between
      TIMP-2 serum levels in patients with adrenal tumours and the control values.
      Significant increase of serum MMP-3 level was found in patients with cortex
      cancer and hormonally active benign adrenocortical tumours. The MMP-3 mean serum
      level was also significantly higher in patients with malignant incidentalomas
      than in those with benign ones. In all groups of patients with adrenal tumours
      the means serum VEGF level was significantly higher than in control patients, and
      it was also significantly higher in patients with malignant incidantalomas than
      in those with benign ones. After surgery the VEGF level decreased significantly
      in patients with extraglandular tumours and cortex cancers who had no recurrence.
      CONCLUSIONS: Since MMP-3 and VEGF serum levels were found significantly higher in
      patients with malignant adrenal incidentalomas than in those with benign ones,
      they might be applied as markers of malignancy of incidentalomas. VEGF and MMP-3
      levels decreased after tumour resection in all patients with malignant tumors and
      increased significantly in patients with recurrence. Therefore, they are supposed
      to be of prognostic value in these patients.

PMID- 11308992
TI  - Sex hormone-binding globulin as a marker of the effect of hormonal treatment in
      Turner's syndrome.
AB  - OBJECTIVE: In girls with Turner's syndrome a positive effect of growth hormone
      (GH) therapy on statutal growth has been well documented, in spite of the fact
      that the levels of GH and IGF-I in these patients are usually within the normal
      range. It is known that plasma levels of sex hormone-binding globulin (SHBG) are
      negatively associated with growth hormone (GH) and with [GF-I. Limited data on
      SHBG levels in these patients and only scarce reports on other than gonadal
      steroids in these patients are available so far. The major aim of this study was
      to find out whether SHBG does respond to GH treatment. METHODS: Plasma levels of
      SHBG, estradiol, progesterone, testosterone and the adrenal steroids and their
      precursors, namely cortisol, 17alpha-hydroxyprogesterone, androstenedione,
      dehydroepiandrosterone and its sulfate were determined in 65 patients aged 2-23
      years with Turner's syndrome. The patients were divided into 4 groups according
      to their actual treatment (untreated, sex steroids only, GH only, GH and sex
      steroids) and the differences between the groups were evaluated. With respect to
      dependence of SHBG and of steroids studied on age (with exception of cortisol),
      their values were expressed as per cents of medians of the physiological values.
      RESULTS: As expected, low levels of sex steroids were found. As to the adrenal
      steroids, in general, their average levels were lower than in healthy subjects
      but still within the physiological limits. With one exception (androstenedione),
      no significant differences were found between the groups. The levels of cortisol
      were undistinguishable from healthy subjects. Absolute as well as relative SHBG
      levels in untreated group and in the group treated with estrogens were normal or
      even lower than those reported for normal subjects of the same chronological age.
      Significantly reduced absolute as well as relative SHBG levels in comparison to
      all other groups were found in GH treated children. CONCLUSION: The results
      indicate that SHBG may serve as a sensitive biochemical marker of the response to
      the GH administration.

PMID- 11308993
TI  - Influence of hemithyroidectomy on bromodeoxyuridine incorporation into DNA of rat
      thyroid follicular cells.
AB  - OBJECTIVE: To examine the bromodeoxyuridine (BrdU) incorporation into DNA of
      thyroid follicular cells (TFC) in the remaining thyroid lobe after
      hemithyroidectomy (hemiTx) in 1, 2, 3 and 4 weeks time after surgery. METHODS:
      The experiment was performed on male Wistar rats. The Cell Proliferation Kit
      (Amersham, UK) was used in order to detect the incorporated BrdU. The BrdU
      incorporation was expressed as a BrdU labeling index (BrdULI; a number of BrdU
      immunopositive TFC per 1000 TFC). RESULTS: 1. No statistically significant
      changes of BrdULI were observed between the particular groups of sham-operated
      (shamTx)-rats in 1, 2, 3 and 4 weeks time after surgery, and in comparison of
      each of them to the controls (at time "0"); 2. In the first 2-week period after
      hemiTx, an increasing effect of that surgical procedure on BrdULI value was
      observed (the highest BrdULI value was detected 2 weeks after hemiTx); 3. In the
      third and fourth week after hemiTx, a decrease of BrdULI value was observed, as
      compared to BrdULI groups (in 1- and 2-week time after hemiTx), and to the
      controls (at time "0"); 4. An increase of weight of contralateral lobe was shown
      in 1, 2, 3 and 4 weeks after hemiTx in comparison to thyroid lobe weight in
      intact rats. CONCLUSIONS: During the first 2 weeks after hemiTx, the thyroid
      growth in the remaining thyroid lobe seems to ensue by hyperplasia mechanisms.
      The thyroid growth processes during subsequent 2 weeks (3rd and 4th) could result
      from other mechanisms - for example, from hypertrophy.

PMID- 11308994
TI  - Radioimmunoassay for somatostatin receptor type 2.
AB  - OBJECTIVE: To develop radioimmunoassay for somatostatin receptor type 2 (SSTR2)
      and search for its presence in certain rat tissues. METHODS: Anti-SSTR2 antiserum
      has been raised in New Zealand white rabbits immunized with a conjugate of
      synthetic SSTR2 with bovine serum albumin. Radioiodination of SSTR2 was performed
      by chloramin T method followed by purification of radioiodinated material on
      Sephadex G-25 column. RESULTS: The obtained antibody did not crossreact with
      SSTR1, SSTR3, SSTR4, SSTR5, hypothalamic hormones, pituitary hormones,
      neuropeptides or gut hormones. The assay was performed with a double antibody
      system. SSTR2 was extracted from the tissues with acid acetone. The dilution
      curve of acid acetone-extracts of rat hypothalamus in the radioimmunoassay system
      was parallel to the standard curve. The recovery of tissue SSTR2 was about 89 %,
      and the intra-assay and inter-assay variations were 4.9 % and 7.8 %,
      respectively. SSTR2 was found in the hypothalamus, cerebrum, cerebellum,
      pituitary, stomach and testis. CONCLUSIONS: These data suggest that this assay
      system is suitable for the estimation of SSTR2 in the tissues.

PMID- 11308995
TI  - Differential responses to stress stimuli of Lewis and Fischer rats at the
      pituitary and adrenocortical level.
AB  - OBJECTIVE: Histocompatible rat strains Lewis (LEW) and Fischer 344 (F344) are
      often used to study hypothalamic-pituitary-adrenocortical axis function in
      relation to immune system activity. It has been suggested that LEW rats have a
      defect in the hypothalamic production of corticotropin-releasing hormone. The aim
      of this study was to clarify differential responsiveness of LEW and F344 rat
      strains to acute stress by measuring adrenocorticotropic hormone (ACTH) and
      corticosterone concentrations in plasma, corticosterone in adrenal cortex and
      proopiomelanocortin (POMC) gene expression in the pituitary and spleen. METHODS:
      Two separate experiments were performed. In the first, indwelling catethers were
      used for blood sampling from conscious animals during immobilization stress. In
      the second experiment, rats were immobilized for two hours and decapitated after
      another 3 hrs for organ collection. RESULTS: Our results show that LEW strain
      hyporeactivity was evident from significantly lower ACTH and corticosterone
      levels compared to those in F344 at all time intervals during stress studied.
      Measurement of POMC gene expression in the pituitary revealed that the difference
      in hormone secretion was consistent with POMC mRNA concentrations in these
      strains of rats. On the other hand, corticosterone concentrations in the adrenal
      cortex after stress were significantly higher in LEW rats compared to F344. No
      differences in spleen POMC mRNA concentrations between LEW and F344 rats were
      found. CONCLUSION: The results show that differential reactivity of LEW and F344
      rats is associated with different POMC gene expression in the pituitary and
      probably other factors on the adrenocortical level.

PMID- 11308996
TI  - Genetic aspects of pheochromocytoma.
AB  - We here review the literature on genetics related to pheochromocytoma. About 10
      percent of these neuroendocrine tumors are hereditary and are most often
      associated with multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau
      disease, and neurofibromatosis type 1 (NF 1). Hereditary tumor syndromes such as
      the aforementioned ones, are ideal to study the molecular pathogenesis of
      tumorigenesis as opposed to sporadic tumors in which genetic alterations often
      merely represent epigenetic tumor progression phenomena. Recent advances in
      molecular genetics, especially of RET, VHL, NF1, and SDHD, helped better
      understand the pathogenesis of pheochromocytoma. In this paper, we not only
      summarize key points of genetic discoveries related to pheochromocytoma, but also
      report in table format all known RET germline mutations related to
      pheochromocytoma.

PMID- 11308997
TI  - Chemically induced carcinogenesis: a comparison of 1-methyl-1-nitrosourea, 7,12
      dimethylbenzanthracene,diethylnitroso-amine and azoxymethan models (minireview).
AB  - The induction of mammary gland and other organ tumours by selected chemical
      carcinogens, 1-methyl-1-nitrosourea, 7,12-dimethylbenzanthracene,
      diethylnitrosoamine and azoxymethane is described and their application in
      experimental carcinogenesis research is discussed.

PMID- 11308998
TI  - Scandinavian intensive care--futility or too few utilities.

PMID- 11308999
TI  - Haemodynamic changes and vasopressin release are not consistently associated with
      carbon dioxide pneumoperitoneum in humans.
AB  - BACKGROUND: Conflicting haemodynamic changes, suggested to be caused by
      vasopressin release, have been reported during carbon dioxide (CO2)
      pneumoperitoneum. However, peritoneal stimulations including open surgery cause
      both a systemic vasopressor response and a vasopressin release, which are
      suppressed by opiate administration. Also, a decreased venous return of blood to
      the heart causes vasopressin release. Furthermore, previous haemodynamic
      assessments of laparoscopic surgery have been conducted using various anaesthetic
      regimens, which are likely to have caused various haemodynamic effects. We
      hypothesised that intraoperative haemodynamic and/or humoral changes would not be
      observed in association with laparoscopic surgery provided that, (a)
      normovolaemia is continuously maintained using transoesophageal echocardiographic
      (TEE) assessment, and (b) adequate depth of general anaesthesia is continuously
      maintained by bispectral index (BIS) monitoring and high plasma Ievel opiate
      administration. METHODS: Twenty ASA 1 women undergoing laparoscopic surgery
      received 10 ml. kg-1 lactated Ringer's solution and thereafter were randomly
      allocated to receive intraoperatively either 8 ng. ml-1 or 4 ng. ml-1 plasma
      remifentanil concentrations while BIS was maintained at 50+/-5 by isoflurane
      alteration. The group receiving 4 ng. ml-1 remifentanil was used as control.
      Expired CO2 was maintained within a 32-38 kPa range throughout the investigation.
      Complete TEE haemodynamic investigation was performed before pneumoperitoneum
      (PP) (T1), and during PP horizontal (T2), with a head-up tilt (T3), with a head
      down tilt (T4), horizontal (T5), and PP released (T6). Plasma vasopressin,
      epinephrine and norepinephrine levels were measured at T1, T3, and T6. ANOVA,
      Student's t-test and Mann-Whitney U-test were used for statistical analysis.
      RESULTS: Haemodynamic indices and humoral values did not change significantly
      within and between remifentanil groups throughout the investigation (all P<0.05).
      CONCLUSION: Continuous adequate depth of anaesthesia and normovolaemia may have
      prevented both a humoral and a haemodynamic response, initiated in the peritoneum
      by the contact with CO2 in previous investigations.

PMID- 11309000
TI  - Long-term infusion of atrial natriuretic peptide (ANP) improves renal blood flow
      and glomerular filtration rate in clinical acute renal failure.
AB  - BACKGROUND: Short-term infusion of atrial natriuretic peptide (ANP) increases
      renal blood flow (RBF) and glomerular filtration rate (GFR) in patients with
      acute renal dysfunction. In the present study we evaluated the effects of long
      term infusion (>48 h) of ANP on (RBF) and (GFR) in 11 postcardiac surgical
      patients requiring pharmacological circulatory support and with acute renal
      impairment. METHODS: Urinary clearance of Cr-EDTA and PAH as well as central
      hemodynamic measurements were performed for 2-3 consecutive 30-min periods during
      ANP infusion (50 ng. kg-1. min-1), one hour after abrupt discontinuation of ANP
      and again immediately after reinstitution of ANP infusion. RESULTS: During ANP
      infusion, urine flow (UF), GFR, RBF and renal vascular resistance (RVR) were
      6.4+/-1.1 ml. min-1, 19.9+/-3.1 ml. min-1, 408+/-108 ml. min-1 and 0.286+/-0.054
      mmHg. min. ml-1, respectively. UF, GFR and RBF decreased significantly by 28%
      (P<0.001), 32% (P<0.01) and 31% (P<0.05), respectively when ANP infusion was
      discontinued. RVR increased by 93% (P<0.05) while there was no change in
      filtration fraction. After reinstitution of ANP infusion, all measured renal
      variables returned to baseline. There was no significant correlation between the
      number of ANP treatment days and the percentage decrease in GFR (r=0.18) or RBF
      (r=0.22) during ANP withdrawal. Central hemodynamic variables were not affected
      by ANP withdrawal. CONCLUSIONS: ANP infusion improves RBF and GFR in patients
      with acute renal impairment after cardiac surgery. This renal vasodilatory effect
      is maintained during a long-term infusion and seems to be hemodynamically safe.

PMID- 11309001
TI  - Risk factors associated with new onset tachyarrhythmias after cardiac surgery--a
      retrospective analysis.
AB  - BACKGROUND: Tachyarrhythmias (TA) represent a frequent and serious problem after
      cardiac surgery. We retrospectively analyzed 987 cardiac surgery patients
      admitted to a surgical intensive care unit between 1996 and 1999 to assess
      incidence and risk factors associated with development of postoperative TA in the
      intensive care unit. METHODS: TA (n=149) were defined as non-sinus rhythm with a
      heart rate (HR) > or =100 bpm in patients with preoperative sinus rhythm or as
      heart rate > or =130 bpm in patients with preoperative atrial fibrillation. A
      total of 787 patients served as controls (C). Demographic, premorbidity and
      perioperative data, admission SAPS and MODS-score, presence of clinical syndromes
      systemic inflammatory response syndrome (SIRS) and sepsis were univariately
      compared between groups. For prediction of independent risk factors for TA
      development two multiple logistic regression models were finally established.
      RESULTS: Concerning TA, atrial fibrillation and flutter (76%) were observed most
      frequently, followed by paroxysmal supraventricular tachycardia (15%) and
      ventricular tachycardia/fibrillation (11%). Age, a history or presence of
      congestive heart failure, development of SIRS and sepsis, severity of multiple
      organ dysfunction syndrome and in particular severity of cardiovascular failure
      proved to be independent risk factors for development of TA. CONCLUSION: In
      cardiac surgery patients, age, a history or presence of congestive heart failure,
      postoperative development of a systemic inflammatory response syndrome or sepsis
      and the severity of multiple organ function syndrome were independent predictors
      for development of TA in the intensive care unit. The association of severity of
      cardiovascular dysfunction with TA strongly suggests a causal relationship
      between catecholamine therapy and TA-development.

PMID- 11309002
TI  - Evaluation of two methods to calculate p50 from a single blood sample.
AB  - BACKGROUND: The hemoglobin-oxygen affinity is conveniently described as the
      oxygen tension at which the hemoglobin is 50% saturated (p50). We compared two
      methods of single-point analysis for p50 calculation, using clinical data.
      METHODS: From patients submitted to anesthesia for major surgery, 114 arterial or
      venous blood samples were analyzed by using the Sigaard-Andersen oxygen status
      algorithm (p50OSA) and Doyle's method (p50Doyle) based on Hill's equation.
      RESULTS: The oxygen saturation and tension varied respectively between 0.64-0.96
      and 3.8 kPa-11.0 kPa. A Bland-Altman analysis showed a mean difference of 0.04
      kPa (SD 0.12 kPa). The limits of agreement were -0.20 kPa and +0.28 kPa.
      CONCLUSIONS: The Siggaard-Andersen oxygen status algorithm is presently the most
      clinically useful single-point method of p50 calculation.

PMID- 11309003
TI  - Computer control versus manual control of systemic hypertension during cardiac
      surgery.
AB  - BACKGROUND: We recently demonstrated the feasibility of computer controlled
      infusion of vasoactive drugs for the control of systemic hypertension during
      cardiac surgery. The objective of the current study was to investigate the
      effects of computer controlled blood pressures on hemodynamic stability when
      compared to conventional manual control. METHOD: Systemic artery blood pressures
      were managed either by computer (80 patients) or by a well-trained
      anesthesiologist (80 patients). The vasodilator drugs sodium nitroprusside and
      nitroglycerin were used. Hemodynamic stability was determined from the standard
      deviation of the mean arterial pressure samples and from the percentages of time
      that arterial pressure was hypertensive or hypotensive. RESULTS: The average
      standard deviation of the mean arterial pressure samples was smaller for the
      computer controlled than for the manually controlled group: 7.5+/-2.2 (mean+/-SD)
      versus 8.9+/-2.3 mmHg (P<0.0001). The systemic artery pressure was less
      hypertensive and less hypotensive in the computer controlled than in the manually
      controlled group: 9.4+/-5.7 versus 13.1+/-6.0% (P<0.0001) and 8.0+/-5.9 versus
      11.8+/-7.4% (P<0.0001), respectively. CONCLUSION: We conclude that, compared with
      manual control, computer control of systemic hypertension significantly improved
      hemodynamic stability during cardiac surgery.

PMID- 11309004
TI  - No impact of a leucocyte depleting arterial line filter on patient recovery after
      cardiopulmonary bypass.
AB  - BACKGROUND: Contact of blood with foreign surfaces in the cardiopulmonary bypass
      (CPB) circuit induces an inflammatory response and immunosuppression which are
      associated with several organ dysfunctions following cardiac surgery. The aim of
      the present study was to evaluate clinical patient recovery after coronary artery
      bypass surgery (CABG) using CPB with leucocyte filtration or no arterial line
      filter. METHODS: Sixty patients scheduled for CABG were randomly assigned to
      undergo CPB with a leucocyte depleting arterial line filter (Pall LG6) or no
      filter. Total leucocyte count and platelet count were determined before and after
      CPB. Values for blood urea nitrogen, serum creatine, serum sodium and potassium,
      serum osmolality, urine creatine, urine sodium and potassium, and urine
      osmolality were recorded at baseline, at 6 h and 24 h after CPB, and on the 5th
      postoperative day. Complement status was evaluated by measuring the levels of C3
      and C4 before surgery and 24 h after CPB. Need for postoperative inotropic
      support was recorded, as was oxygen index prior to and after tracheal extubation.
      Times to awakening and tracheal extubation were noted, as were length of stay at
      the intensive care unit (ICU) and the hospital. Amount of chest drainage until 24
      h and need for red blood cell transfusions were recorded. RESULTS: The level of
      C3 at 24 h was significantly lower in LG6-patients, but no further differences
      were detected between the groups in any of the laboratory or clinical parameters
      except for greater chest drainage in LG6-patients. However, need for red blood
      cell transfusions was similar in both groups. CONCLUSION: Leucocyte filtration in
      our elective CABG patients did not have any impact on pulmonary gas exchange,
      need for postoperative inotropic support, length of postoperative mechanical
      ventilation, or length of ICU or hospital stay.

PMID- 11309005
TI  - Impact of enteral feeding on gastric tonometry in healthy volunteers and
      critically ill patients.
AB  - BACKGROUND: Enteral feeding may interfere with gastric tonometry measurement. The
      effect of enteral nutrition on gastric tonometry has not been fully documented.
      METHODS: Seven healthy volunteers and nine stable intensive care unit (ICU)
      patients with poor tolerance of gastric feeding were investigated. Consecutive
      continuous postpyloric and gastric feeding, both at two different rates (40 and
      100 ml. h-1, respectively), and an intragastric 200 ml nutrition bolus were
      studied. Gastric intramucosal PCO2 (PiCO2) was measured by air tonometry and in
      patients a gastric intramucosal-arterial PCO2 difference (PCO2 gap) was
      calculated. Hemodynamics and blood gases were also measured. RESULTS: In
      volunteers, PiCO2 remained stable during the postpyloric phase. During continuous
      gastric feeding PiCO2 did not change significantly, although in 4 volunteers
      PiCO2 increased >0.5 kPa. PiCO2 decreased significantly after gastric bolus from
      6.9+/-0.4 to 6.1+/-0.5 kPa (P<0.05). Eight patients had an increased PCO2 gap (>1
      kPa) at baseline (1.8+/-0.6 kPa). PCO2 gap changes during the whole study were
      not statistically significant. However, during the postpyloric phase (or
      immediately afterwards), the PCO2 gap increased by more than 0.5 kPa in 5
      patients. After gastric bolus, a decrease in PCO2 gap >0.5 kPa was seen in 5
      patients. CONCLUSION: In volunteers, postpyloric feeding does not interfere with
      gastric tonometry measurement and gastric bolus leads to a PiCO2 decrease. The
      impact of postpyloric and gastric feeding on gastric tonometry in ICU patients
      with compromised gut is variable.

PMID- 11309006
TI  - Inhibitory effects of S-(-) and R-(+) bupivacaine on neutrophil function.
AB  - BACKGROUND: Local anesthetics inhibit migration, enzyme release and superoxide
      anion generation of polymorphonuclear leukocytes (PMN). Due to their ability to
      phagocytose and kill bacteria PMN represent a major defense mechanism in the
      circulating blood. In this study we determined the influence of racemic
      bupivacaine and its enantiomers on neutrophil phagocytic activity, oxidative
      burst as well as surface expression of complement and Fcgamma receptors. METHODS:
      Venous blood was pre-incubated with different concentrations of either racemic
      bupivacaine, R-(+) or S-(-) bupivacaine. Fluoresceine isothiocyanate (FITC)
      labeled antibodies against Fcgamma receptor III (CD16), complement receptor 1
      (CD35) and complement receptor 3 (CD11b) were used to determine surface receptor
      expression. Phagocytic activity was measured by ingestion of FITC-labeled vital
      Staphylococcus aureus. Oxidative burst was determined by conversion of
      nonfluorescent dihydrorhodamine 123 into fluorescent rhodamine 123. Fluorescent
      intensity of each sample was determined by flow cytometry. RESULTS: Racemic
      bupivacaine inhibited surface receptor expression, phagocytosis, and oxidative
      burst in a time- and concentration-dependent manner. Although the S-(-)
      enantiomer exerted significantly less inhibitory action on neutrophil function
      compared to R-(+) and racemic bupivacaine, these effects were small compared to
      the overall changes. CONCLUSION: These findings suggest that bupivacaine impairs
      surface receptor expression and may thereby contribute to reduced phagocytic
      activity and oxidative burst. Enantiomer-specific effects of bupivacaine may play
      a minor role in the inhibition of these leukocyte functions.

PMID- 11309007
TI  - A bilateral clinical model for the study of acute and chronic pain after breast
      reduction surgery.
AB  - BACKGROUND: There is a need for new clinical models to investigate effectively
      the development of pain after surgery and the effect, if any, of pre-emptive
      treatment. Bilateral models are of special interest, since the patient serves as
      his/her own control. The objective of this preliminary study was to test a
      clinical model for the study of acute and chronic pain after bilateral reduction
      mammoplasty. METHODS: Eight patients participated in the study where the breasts
      were randomized to test and control groups. In each patient, one breast was
      preoperatively infiltrated with lidocaine and adrenaline and the other breast
      infiltrated with saline and adrenaline. Assessment included visual analogue scale
      (VAS) pain intensity, thermal thresholds, mapping for punctate hyperalgesia and
      tactile sensation. Assessments were made preoperatively, postoperatively and at 6
      months after surgery. RESULTS: With regard to acute postoperative pain intensity,
      the model demonstrated a clear difference between lidocaine and placebo treated
      breasts. There was no difference between lidocaine and placebo treated breasts
      with regard to chronic pain, but these results are inconclusive due to small
      number of patients. CONCLUSION: The model is sensitive and may be useful in
      studies of mechanisms of development and prevention of chronic pain after
      surgery.

PMID- 11309008
TI  - Inclusion of lignocaine base into a polar lipid formulation--in vitro release,
      duration of peripheral nerve block and arterial blood concentrations in the rat.
AB  - BACKGROUND: Slow-release formulations of local anaesthetics may produce nerve
      blocks of long duration. The present study aimed at investigating the in vitro
      and in vivo properties of a polar lipid formulation for slow release of
      lignocaine and the effects on nerve block duration by inclusion of dexamethasone
      into the system. METHODS: In vitro release of lignocaine from the lipid
      formulation was studied in a US Pharmacopoeia rotating apparatus. Sciatic nerve
      blocks were induced in rats by 0.1 ml of test formulations containing lignocaine
      HCl 20 mg. ml-1 in aqueous solution, lignocaine base 20, 100 or 200 mg. ml-1 in
      lipid formulation or the last formulation with dexamethasone 0.05, 0.5 or 5 mg.
      ml-1. The durations of sensory and motor block and the arterial blood
      concentrations of lignocaine were investigated. RESULTS: In vitro there was a
      sustained release of lignocaine from the lipid formulation, with 50% release at
      around 48 h. In vivo lignocaine base 20 mg. ml-1 in lipid formulation produced
      sciatic nerve blocks of significantly shorter duration than lignocaine HCl 20 mg.
      ml-1 in aqueous solution, while lignocaine base 100 and 200 mg. ml-1 in lipid
      formulation produced blocks lasting two and three times longer, respectively,
      than the lignocaine HCl solution. Addition of dexamethasone did not affect the
      duration of nerve block. Following administration of lignocaine base 200 mg. ml-1
      in lipid formulation, as compared to lignocaine HCl 20 mg. ml-1 in aqueous
      solution, the maximal blood concentration of lignocaine was only three times
      higher in spite of the ten-fold difference in dose, and the mean terminal half
      life was three times longer, reflecting the slow release from the formulation.
      CONCLUSIONS: Our findings indicate that lignocaine base in polar lipids acts as a
      slow-release preparation of local anaesthetic both in vitro and in vivo.

PMID- 11309009
TI  - Fentanyl does not improve the nerve block characteristics of axillary brachial
      plexus anaesthesia performed with ropivacaine.
AB  - BACKGROUND: The aim of this prospective, randomized, double-blind study was to
      evaluate the effects of adding 1 microg. kg-1 fentanyl to ropivacaine 7.5 mg. ml
      1 for axillary brachial plexus anaesthesia. METHODS: With Ethics Committee
      approval and written consent, 30 ASA physical status I-II in-patients, scheduled
      for orthopaedic hand procedures were randomly allocated to receive axillary
      brachial plexus block with 20 ml of either ropivacaine 7.5 mg. ml-1 (n=15) or
      ropivacaine 7.5 mg. ml-1+1 microg. ml-1 fentanyl (n=15). Nerve blocks were placed
      using a nerve stimulator with the multiple injection technique. A blinded
      observer recorded the time to onset of surgical block (loss of pinprick sensation
      in the innervation areas of the hand (C6-C8) with concomitant inability to flex
      the wrist against gravity and move the fingers when squeezing the hand) and first
      request for pain medication after surgery. RESULTS: No differences in demography,
      degree of sedation or peripheral oxygen saturation were observed between the two
      groups. Median (range) time required to achieve readiness for surgery was 15 min
      (5-36 min) with ropivacaine alone and 15 min (5-40 min) with the ropivacaine
      fentanyl mixture. No differences in the intraoperative quality of nerve block
      were reported between the two groups. Four patients receiving ropivacaine plain
      and two patients receiving the ropivacaine-fentanyl mixture did not require
      analgesics during the first 24 h after surgery (P=0.62). The degree of pain
      experienced at first analgesic request in those patients asking for pain
      medication, as well as median consumption of postoperative analgesics, were
      similar in the two groups. First postoperative analgesic request was made at 11 h
      (25th-75th percentiles: 9.1-14 h) in patients receiving ropivacaine alone and at
      11.8 h (25th-75th percentiles: 9.8-15 h) in patients receiving the ropivacaine
      fentanyl mixture (P=0.99). CONCLUSION: The addition of fentanyl 1 microg. ml-1 to
      ropivacaine 7.5 mg. ml-1 does not improve the nerve block characteristics of
      axillary brachial plexus anaesthesia for orthopaedic procedures involving the
      hand.

PMID- 11309010
TI  - Ropivacaine 1 mg/ml, plus fentanyl 2 microg/ml for epidural analgesia during
      labour. Is mode of administration important?
AB  - BACKGROUND: Patient-controlled epidural analgesia (PCEA) with a moderate to high
      concentration of bupivacaine in obstetrics has been shown to give comparable
      analgesia and even higher level of satisfaction compared to continuous epidural
      infusion. We hypothesised that the use of a very low concentration technique
      (ropivacaine/fentanyl) might result in excessive dosing in the PCEA group, more
      motor blockade and a negative impact on spontaneous delivery rate. METHODS: We
      conducted a randomised, double-blind study of 60 nulliparous women at term
      comparing low concentration ropivacaine/fentanyl administered in either patient
      controlled or fixed continuous infusion mode. Parturients with known predictors
      of painful deliveries, i.e. breech presentation, primary induction of labour,
      were not included. Deliveries within 90 min from the start of epidural analgesia
      were omitted from the evaluation. RESULTS: We found that both groups required a
      mean of 12 ml/h low concentration mixture (loading and midwife rescue boluses
      included). There was no difference between groups with respect to spontaneous
      delivery rate (71%). This low concentration technique resulted in haemodynamic
      stability without crystalloid preloading, infusion or vasopressor use. Motor
      blockade of clinical importance was not detected in any patient. CONCLUSION: We
      conclude that epidural use of ropivacaine 1 mg/ml+fentanyl 2 microg/ml provides
      effective analgesia with equal volume requirements irrespective of administration
      mode, with a high spontaneous delivery rate. Choice of PCEA or CEI (continuous
      epidural infusion) should be directed by other considerations, most importantly
      compliance of midwife and possible reduction in workload for anaesthesiology
      staff.

PMID- 11309011
TI  - Intraocular pressure and ropivacaine in peribulbar block: a comparative study
      with bupivacaine.
AB  - BACKGROUND: The aim of this study was to compare the effects on intraocular
      pressure (IOP) of ropivacaine and bupivacaine in peribulbar block. METHODS: The
      study involved 40 patients with ASA physical status I, II or III undergoing
      cataract surgery under peribulbar block. Patients were allocated to two groups
      according to the local anesthetic used: Group R (n=20), 1.0% ropivacaine and
      Group B (n=20) 0.75% bupivacaine, both associated with 50 IU. ml-1 hyaluronidase,
      in peribulbar double injection technique. IOP was measured at four time points:
      0=before block (control); 1=1 min after block; 2=5 min after block; 3=15 min
      after block. RESULTS: Mean values of IOP (mm Hg) after block were significantly
      lower in Group R in comparison to Group B: time point 1=13.4+/-3.2 vs 20.8+/-4.7;
      time point 2=10.9+/-3.7 vs 14.4+/-3.8; time point 3=7.7+/-4.0 vs 10.5+/-3.1. The
      variation of IOP was different in each group. In Group R, the mean values
      obtained at the three time points after block were significantly lower than the
      control; in Group B, the mean value of IOP rose significantly 1 min after block
      and was lower than control only at time point 3. CONCLUSIONS: Ropivacaine 1.0%
      associated with hyaluronidase in peribulbar block is better than 0.75%
      bupivacaine under the same standard conditions for lowering IOP in intraocular
      surgery. This effect is probably due to relaxation of the extraocular muscles
      after the block with both anesthetics, and possibly to a smaller intraocular
      blood volume due to vasoconstriction in the case of ropivacaine.

PMID- 11309012
TI  - Effect of preincisional ilioinguinal and iliohypogastric nerve block on
      postoperative analgesic requirement in day-surgery patients undergoing
      herniorrhaphy under spinal anaesthesia.
AB  - BACKGROUND: By choosing spinal anaesthesia instead of general anaesthesia, and by
      infiltrating the wound area with local anaesthetic the need for postoperative
      analgesics may be reduced. An ilioinguinal and iliohypogastric nerve block (IINB)
      in inguinal herniorrhaphy was, therefore, studied in a day surgery setting in
      combination with a spinal block. METHODS: One hundred ASA I-II adult patients
      scheduled for inguinal herniorrhaphy were given spinal anaesthesia with
      hyperbaric 0.5% bupivacaine. In a randomized and blinded fashion half of them
      received an IINB 5 min before the surgical incision with 10 ml of 0.5%
      bupivacaine (B-IINB) and the other half with saline (S-IINB). All patients
      received ketoprofen 100 mg i.v. during surgery and another 100 mg 2-3 h
      postoperatively. The patients were observed for about 6 h in the day surgery unit
      before discharge. RESULTS: The results showed that in comparison with the S-IINB
      group, significantly fewer patients in the B-IINB group needed analgesics
      (P<0.01) and the amount required was also significantly less postoperatively,
      before discharge (about 6 h postoperatively) (P<0.05). The latency to the need
      for the first postoperative analgesic was shorter in the S-IINB patients
      (P<0.01). At home the VAS scores and the need for analgesics (oral ketoprofen 100
      mg) were low with no differences between the groups. No complications occurred.
      CONCLUSION: It is concluded that no long-term analgesia could be demonstrated by
      a preincisional IINB performed during spinal anaesthesia in day-surgery inguinal
      herniorrhaphy patients. Thus, reduced analgesic requirement was seen only for
      about 6 h postoperatively.

PMID- 11309013
TI  - Distribution of intrathecal catheter positions in rat.
AB  - BACKGROUND: Although drug administration through an intrathecal catheter is
      widely used in the study of spinal pharmacology, the catheter positions in
      transverse plane that may cause a limited spread of a solution remain unclear. In
      the first step to clarify this issue, the distribution of the intrathecal
      catheter position was investigated in rats. METHODS: A polyethylene catheter (PE
      10) was inserted intrathecally 8.5 cm through the atlanto-occipital membrane,
      aiming the tip of the catheter to the dorsal surface of the spinal cord. Three or
      four weeks after the implantation of the catheter, 83 rats were transcardiacally
      perfused with fixative solution. The catheter positions were investigated
      longitudinally and transversely by cutting the spinal cord segmentally through
      the intervertebral disk at different spinal levels. RESULTS: Seventeen rats were
      excluded from further data analysis. Transversely, catheters were located in the
      left lateral subarachnoid space in 23 rats (35%), in the right lateral in 15
      (23%), in the dorsal in 22 (33%), and in the ventral in 6 (9%). Longitudinally,
      catheter position was significantly higher in the ventral group (median, T9) than
      that in the dorsal group (T11/12) (P<0.01). CONCLUSION: Chronic intrathecal
      catheters were variously located in the rat spinal subarachnoid space in the
      transverse plane, and lateral subarachnoid placement of the catheter (58%) was
      frequently observed, whereas dorsal subarachnoid placement occurred in 33%.

PMID- 11309014
TI  - Onset and duration of action of rocuronium--from tracheal intubation, through
      intense block to complete recovery.
AB  - BACKGROUND: The primary objective of this study was to establish the relation
      between the post tetanic count (PTC) and the time to reappearance of the first
      response (T1) in train-of-four (TOF) nerve stimulation following rocuronium 0.6
      mg/kg, 0.9 mg/kg, and 1.2 mg/kg. The secondary objective was to evaluate the
      intubation conditions after 1 min. METHODS: One hundred and eight patients were
      randomised to one of three doses of rocuronium: 0.6, 0.9 or 1.2 mg/kg. Tracheal
      intubation was performed at 60 s by a blinded investigator. During propofol,
      fentanyl, midazolam anaesthesia the neuromuscular block was monitored by
      mechanography using TOF stimulation every 12 s. At 6 min intervals, a tetanic
      stimulation (50 Hz) was applied for 5 s preceded and followed by a 30 s period of
      1 Hz stimulation until the reappearance of T1. RESULTS: There was a significant
      difference in recovery following the high dose and the two lower doses. The
      relation between time (min) to reappearance of T1 (t) and PTC can be expressed as
      follows: t(0.6 and 0.9 mg/kg)(min)=18.8-6.46 PTC and t(1.2 mg/kg)(min)=26.1-9.12
      PCT. T1 was seen at a mean PTC level of 8 or 9 in all three groups. The
      intubation conditions were graded as excellent or good in all patients except in
      two patients following the 0.6 mg/kg dose of rocuronium. CONCLUSION: The PTC
      method can be used to predict the time to first response to TOF nerve stimulation
      during intense rocuronium induced neuromuscular blockade. The relation between
      PTC and the time to T1 was prolonged after 1.2 mg/kg compared with 0.6 mg/kg and
      0.9 mg/kg. No further improvement in intubation conditions at 60 s was evident by
      increasing the rocuronium dose from 0.9 mg/kg to 1.2 mg/kg.

PMID- 11309015
TI  - Does discontinuation of desflurane at the time of neostigmine administration
      speed recovery from cisatracurium block compared to that with a propofol-based
      technique?
AB  - BACKGROUND: Volatile anaesthetics are known to influence the effect of
      neostigmine as an antagonist of neuromuscular block. The aim of the present study
      was to investigate whether discontinuation of desflurane at the time of
      neostigmine administration shortens reversal time from cisatracurium block,
      compared to that with a propofol-based anaesthesia. METHODS: Ten volunteers were
      studied twice. For one study, anaesthesia was induced with alfentanil and
      propofol and maintained with nitrous oxide 70% and propofol 150 microg. kg-1. min
      1. For the other study, experimental conditions were replicated except that
      desflurane 6% was administered and the dose of propofol was only 50 microg. kg-1.
      min-1. The evoked mechanical response of the adductor pollicis to train-of-four
      (TOF) stimulation was recorded. Neuromuscular block was induced with
      cisatracurium 0.2 mg. kg-1. When the magnitude of the first TOF response (T1) had
      recovered to 10%, the block was antagonized with neostigmine 70 microg. kg-1. At
      this time, propofol was decreased to 50 microg. kg-1. min-1, or the desflurane
      was discontinued. RESULTS: There were no significant differences between the two
      techniques of anaesthesia in the rate of neostigmine-induced recovery of the TOF
      ratio. The times (mean+/-SD) to achieve TOF ratios of 0.7, 0.8, and 0.9 were
      (propofol first, desflurane second) 6.1+/-2.2 and 6.5+/-1.6 min; 10.4+/-4.2 and
      9.6+/-2.7 min; 17.1+/-6.9 and 21.0+/-13.0 min, respectively. CONCLUSION:
      Discontinuing desflurane does not speed neostigmine-induced recovery from
      cisatracurium neuromuscular block, when compared to that during propofol-based
      anaesthesia.

PMID- 11309016
TI  - Ease of laryngeal passage during fibreoptic intubation: a comparison of three
      endotracheal tubes.
AB  - BACKGROUND: The use of a fibreoptic bronchoscope to facilitate endotracheal
      intubation is well established in modern anaesthetic practice. Difficulty may be
      encountered when inserting an endotracheal tube over the fibrescope as the
      bevelled tip can impinge on the vocal cords or epiglottis and impede advancement
      through the laryngeal inlet. Intavent have recently developed a tapered tip tube
      for use with their Intubating Laryngeal Mask Airway. A randomised, double-blind
      study was performed to compare the ease of railroading three different tubes over
      a fibrescope placed in the trachea. METHODS: We studied 54 patients presenting
      for elective dental surgery. General anaesthesia was induced with propofol 2-3
      mg/kg, fentanyl 1-1.5 microg/kg, and atracurium 0.5 mg/kg and maintained with
      oxygen (5 l/min) and isoflurane 1-2%. Nasotracheal fibreoptic intubation was
      attempted in all patients. In each case the ease of tube advancement over the
      fibrescope and into the trachea was evaluated by the blinded observer, using the
      classification system (Grade 0-2) described by Jones et al. RESULTS/CONCLUSION:
      The Intavent tube was found to be superior for nasotracheal fibreoptic intubation
      to either the Mallinckrodt reinforced tube (P<0.034) or the Portex Blue Line tube
      (P<0.004).

PMID- 11309017
TI  - Clonidine decreases intraoperative bleeding in middle ear microsurgery.
AB  - BACKGROUND: The antihypertensive drug clonidine is a centrally acting alpha2
      agonist useful as a premedicant because of its sedative, anxiolytic, and
      analgesic properties. We examined the effect of clonidine given as an oral
      preanesthetic medication in producing a bloodless surgical field in patients
      undergoing middle ear microsurgery. We also evaluated whether the administration
      of clonidine would alter the reflex cardiovascular response to laryngoscopy and
      endotracheal intubation, anesthetic requirement, postoperative pain intensity and
      consumption of analgesics, and pre- and postoperative sedation and anxiety.
      METHODS: A prospective, randomized, double-blind clinical trial was performed in
      40 patients scheduled for elective middle ear surgery under general anesthesia.
      Twenty-one patients received clonidine (300 microg p.o.) 90 min prior to arrival
      at the operating theater and 19 received placebo (control group). The hemodynamic
      endpoint of the anesthetic management was maintenance of hypotension for
      producing a bloodless surgical field. The desired control of the cardiovascular
      system was attained with isoflurane (inspired concentration increments of 0.25
      vol% up to a maximum of 1.5 vol%)+/-fentanyl (bolus of 1 microg. kg-1)+/-urapidil
      (bolus of 0.3 mg. kg-1) as needed. Intraoperative bleeding was assessed on a four
      point scale from 0=no bleeding to 3=abundant bleeding. RESULTS: There was less
      bleeding in the clonidine group (mean+/-SEM) than in the control group (0.75+/
      0.3 vs 1.1+/-0.4, P<0.05). Patients given clonidine required a mean inspired
      isoflurane concentration of 0.63+/-0.1 vol% as compared with 1.01+/-0.2 vol% in
      controls (P<0.05). Fentanyl requirements were also significantly lower (57.10 vs
      79.42 microg. kg-1, P<0.05). Four clonidine-treated patients required urapidil to
      achieve satisfactory hypotension as compared with 11 controls (P<0.05). Clonidine
      attenuated the associated cardiovascular response following laryngoscopy and
      intubation, and was more effective than placebo in achieving a satisfactory
      preoperative sedation and decreasing intensity of postoperative pain.
      Preoperative anxiety and incidence of adverse events was similar in both groups.
      CONCLUSION: Premedication with clonidine reduced bleeding in middle ear
      microsurgery, attenuated hyperdynamic response to tracheal intubation, and
      reduced isoflurane, fentanyl, and urapidil requirements for controlled
      hypotension.

PMID- 11309018
TI  - Coagulation assessment in healthy pigs undergoing single xenon anaesthesia and
      combinations with isoflurane and sevoflurane.
AB  - BACKGROUND: With the introduction of new anaesthetics into clinical practice
      possible side effects of these novel anaesthetics have to be evaluated. This
      study was performed to clarify whether xenon or combinations of xenon with
      isoflurane or sevoflurane modify blood coagulation. METHODS: The study was
      performed in 20 healthy pigs which first underwent xenon anaesthesia (65 Vol%)
      and were then randomly assigned to combinations of xenon and isoflurane or
      sevoflurane at varying concentrations. During anaesthesia the following
      parameters were controlled: aPTT, PT, fibrinogen concentrations and
      thrombelastographic measurements. RESULTS: Xenon monoanaesthesia did not alter
      significantly any coagulation parameter. When isoflurane was introduced the aPTT
      showed a significant increase while fibrinogen concentration decreased. The
      introduction of sevoflurane led also to a decrease in fibrinogen concentration,
      while the aPTT was unchanged. These decreases in fibrinogen concentration were
      not accompanied by reduced maximal clot strength or elevated fibrinolysis
      evaluated by thrombelastography. Although the above-described changes were
      statistically significant, none of the parameters throughout the experiment
      exceeded the limits of normal values. CONCLUSION: In our study, xenon
      monoanaesthesia and combinations of xenon with isoflurane and sevoflurane did not
      lead to pathologic alterations in the measured coagulation parameters.

PMID- 11309019
TI  - Similar haemodynamic, respiratory and metabolic changes with the use of
      sevoflurane or halothane in children breathing spontaneously via a laryngeal mask
      airway.
AB  - BACKGROUND: In preschool children, short-lasting surgical procedures are often
      performed under combined inhalational and regional anaesthesia with the child
      breathing spontaneously via a laryngeal mask airway (LMA). Despite widespread
      use, only limited data are available on haemodynamic, respiratory and metabolic
      effects of sevoflurane and halothane during LMA anaesthesia. METHODS: In an open
      label, randomised, controlled study, 49 children (aged 3-8 years) were allocated
      to receive either sevoflurane or halothane in 60% nitrous oxide. After insertion
      of the LMA, end-tidal concentrations of sevoflurane or halothane were maintained
      at 1 MAC with the child ventilating spontaneously throughout the entire
      procedure. Analgesia was provided by caudal block. Haemodynamic and respiratory
      parameters were recorded, and capillary blood-gas samples were obtained
      repeatedly. RESULTS: Changes in heart rate (HR) and systolic blood pressure were
      similar in both groups during all observed periods, apart from a significantly
      higher increase in HR during inhalational induction with sevoflurane (P<0.05).
      Regression slope analysis during anaesthesia revealed a decrease of the
      respiratory rate of 5 breaths h-1 (P<0.001) and an increase of end-tidal PCO2 and
      capillary PCO2 of about 0.25 kPa h-1 (P<0.001), with no significant difference
      between the two groups. Base excess, calculated in capillary blood gas samples,
      did not change over time (P>0.5) in either group. CONCLUSIONS: The use of
      approximately 1 MAC sevoflurane or halothane in 60% N2O in children breathing
      spontaneously via LMA resulted in comparable haemodynamic, respiratory and
      metabolic changes, and clinically relevant deteriorations did not occur during
      the 65-min study period.

PMID- 11309020
TI  - Laryngeal papillomatosis with airway obstruction in an infant.
AB  - Laryngeal papillomatosis in infants and children is a benign condition, but the
      location and a marked tendency for recurrence makes the disease both dangerous
      and troublesome. This case report deals with a little girl who had suffered
      hoarseness and wheezing since she was born. The diagnosis of laryngeal
      papillomatosis was made when she was 17 months old. By that time, the tumour had
      reached a size that necessitated a tracheotomy to secure the airway. The symptoms
      and differential diagnoses are discussed, and it is stressed that chronic
      hoarseness and wheezing sounds in infants and children should make a doctor
      suspect laryngeal papillomatosis. Laser treatment and anaesthetic management of
      small children with a compromised airway are discussed. As tracheal intubations
      and tracheotomy increase the risk of the disease spreading to the trachea and
      bronchi, an example is given of treating laryngeal papillomatosis with potassium
      titanyl phosphate (KTP) laser, using a laryngeal mask as an airway to avoid
      tracheal intubation. Whether this procedure can reduce the need to perform a
      tracheotomy in some of these small patients remains to be seen.

PMID- 11309021
TI  - Computerized tomography-guided epidural blood patch in the treatment of
      spontaneous low cerebrospinal fluid pressure headache.
AB  - A 54-year-old woman suffering from migraine for 35 years was referred to the pain
      clinic with a changed pattern of headache that had developed over the last 6
      weeks. The pain was located in the central forehead region; aggravation in the
      prone and immediate relief in the supine position led to the hypothesis of a
      spontaneous low cerebrospinal fluid (CSF) pressure headache. Cisternography
      revealed a cyst-like formation in the cervico-thoracic region, indicating
      cerebrospinal fluid leakage. Magnetic resonance imaging (MRI) myelography
      confirmed ventral leakage but failed to locate the exact site. Computerized
      tomography (CT)-guided epidural blood patching between T1 and T2 completely
      relieved the headache.

PMID- 11309022
TI  - New local anaesthetics--how much is improved safety worth?

PMID- 11309023
TI  - Heparin-induced thrombocytopenia thrombosis.

PMID- 11309024
TI  - Should central venous catheters, with the tip accidentally placed retrograde in
      the internal jugular vein, be corrected.

PMID- 11309025
TI  - Mask ventilation with esophageal intubation.

PMID- 11309027
TI  - Nail apparatus melanoma.
AB  - Nail apparatus melanoma is a relatively rare variant of melanoma with a
      disproportionately high mortality when compared with melanoma elsewhere. The
      aetiology and natural history remain poorly understood. There is no clear
      epidemiological association with race, skin type or sun exposure. Universally
      accepted clinical and histological criteria for the diagnosis of early nail
      apparatus melanoma have not been defined. The two cardinal clinical signs are
      melanonychia striata and Hutchinson's sign. These are useful but not
      pathognomonic of melanoma. Diagnostic delay is frequent and patients commonly
      have advanced disease at the time of diagnosis. Surgical excision is advocated
      for treatment of stage I disease; however, the most appropriate re-excision
      margins, including the level of amputation where required, have not been
      determined. Early diagnosis and excision of the tumour is the only treatment
      known to increase survival. Adjuvant systemic chemotherapy, isolated limb
      perfusion, and routine elective lymph node dissection have been used, but no
      survival benefit has been demonstrated.

PMID- 11309028
TI  - Post-acne scarring: a short review of its pathophysiology.
AB  - The onset of acne is an expected phenomenon in adolescence. However, its arrival
      produces long-term psychological and physical sequelae for the individual. A
      review of available data illustrates the pathophysiological sequence of the
      advent of post-acne scarring from its humble beginnings as a microscopic comedone
      to its eventual devastating end point of indented or exophytic scars. Acne
      scarring shows many different forms and is explainable by the depth and severity
      of the antecedent inflammation and the ability of the individual to heal these
      lesions. Post-acne scarring is debilitating and socially disabling for many and
      is the avoidable outcome of untreated or inadequately treated acne. Treatment
      will depend on the resultant scar topography.

PMID- 11309029
TI  - Bexarotene capsules and gel for previously treated patients with cutaneous T-cell
      lymphoma: results of the Australian patients treated on phase II trials.
AB  - Bexarotene (Targretin, LGD1069) is a novel synthetic retinoid analogue that binds
      selectively to retinoid X receptors. We describe eight previously treated
      patients who entered phase II international multicentre studies examining the
      role of bexarotene in cutaneous T-cell lymphoma. Patients received either the
      oral formulation (n = 7) or the topical gel (n = 1). Of the seven patients who
      received 300 mg/m2 per day capsules, five (71%) achieved a partial response, with
      mean time to onset of response of 27 days (range, 20-29) with responses
      persisting for a mean of 92 days (range, 57-115). The single patient receiving
      the topical preparation (stage IB) remains in partial response at 31 months. The
      major toxicity with oral administration was hypertriglyceridaemia requiring
      therapy. Bexarotene capsules and gel are active and generally well-tolerated
      agents in patients with cutaneous T-cell lymphoma and studies examining its role
      in previously untreated patients or as part of combination therapy are warranted.

PMID- 11309030
TI  - Perceptions of acne vulgaris in final year medical student written examination
      answers.
AB  - Misconceptions exist in the community regarding factors that exacerbate acne
      vulgaris. In particular stress, diet, lifestyle and personal hygiene are often
      erroneously claimed to be important factors. In order to investigate whether
      these common misconceptions persist in medical graduates, we analysed the answers
      of 215 sixth year medical students, who all subsequently graduated from The
      University of Melbourne, to a short-answer question on acne management and
      exacerbating factors in one of their final year examination papers. With respect
      to exacerbating factors, 67% of students identified stress, 10% identified
      lifestyle factors (smoking and alcohol consumption), and 25% claimed poor facial
      hygiene exacerbated acne. Diet was stated to be an important factor by 41% of
      students, of whom 12% specifically mentioned chocolate. Persistence of these
      misconceptions among medical graduates is likely to perpetuate misinformation in
      the community.

PMID- 11309031
TI  - Long-term patient satisfaction with cosmetic outcome of minor cutaneous surgery.
AB  - We evaluated our patients' own assessment of the cosmetic outcome of minor
      dermatological surgery procedures. A postal questionnaire was sent to patients
      who had undergone surgery between 12 and 18 months previously. Patient
      satisfaction was correlated with variables, including age, sex, lesion size and
      site, indication for excision, histological diagnosis and operator. Two hundred
      and seven excisional procedures were identified in 193 patients. Seventy-nine per
      cent of the questionnaires (163/207) were returned. Seventy per cent of patients
      reported that the scar was invisible or better than expected and 9% rated it to
      be worse than expected. Ninety per cent of patients said they would undergo the
      procedure again. Patient dissatisfaction was associated significantly and
      independently with excisions from the back, younger age and benign histology.

PMID- 11309032
TI  - Treatment of refractory hand warts by isolated limb infusion with melphalan and
      actinomycin D.
AB  - We present an immunocompetent man with extensive warts on the hands, refractory
      to a number of conventional treatment modalities and causing substantial
      morbidity and impairment of normal function. Isolated limb infusion (regional
      intra-arterial chemotherapy) with melphalan and actinomycin D was performed, with
      substantial clearing of the warts within 2 months. Treatment-induced morbidity
      was limited to mild local erythema and oedema which resolved within 3 weeks.
      After 9 months' follow up, the patient had only a few residual warts and was able
      to resume normal activities.

PMID- 11309033
TI  - Subacute cutaneous lupus erythematosus associated with hepatocellular carcinoma.
AB  - A 63-year-old man with a 4-year history of metastatic hepatocellular carcinoma
      secondary to chronic hepatitis B developed a rash affecting his arms, legs,
      thorax and back. Both clinical and histological examination suggested a diagnosis
      of subacute cutaneous lupus erythematosus (SCLE). The association of SCLE and
      hepatocellular carcinoma has not previously been reported. The SCLE persisted
      without remission and was still present at his death from metastatic
      hepatocellular carcinoma 3 months later. We also review other reported cases of
      SCLE as paraneoplastic dermatoses and apply McLean's criteria for paraneoplastic
      dermatosis.

PMID- 11309034
TI  - Therapeutic undermining of scars (Subcision).
AB  - Two patients are described with depressed atrophic scars. The first patient had
      undergone skeletal traction around the knee and the second patient developed an
      apparent anetoderma of the left side of the nose. Dermal undermining was
      performed as the only treatment with successful resolution of their contour
      abnormalities. Only a single treatment session was required in each case. A brief
      review of this technique is presented.

PMID- 11309035
TI  - Allergic contact dermatitis to cinchocaine.
AB  - A case of allergic contact dermatitis to cinchocaine is presented to highlight
      the confusion regarding the classification of, and cross-reactivity between,
      topical anaesthetic agents and the inadequacy of the use of benzocaine as a
      single screening agent for topical anaesthetic contact allergy. Our patient
      presented with a 10-day history of acute perianal dermatitis. Allergic contact
      dermatitis to Proctosedyl ointment, which was applied for 3 weeks prior, was
      suspected. On patch testing, he reacted to cinchocaine, a constituent of
      Proctosedyl ointment, and to the actual product, but had no reaction to
      benzocaine or lignocaine.

PMID- 11309036
TI  - Concurrent pilomatrix carcinoma and giant pilomatrixoma.
AB  - A 52-year-old man presented with a large, fungating mass on the inner aspect of
      his left thigh and a smaller hard mass on the inner aspect of his left knee with
      normal overlying skin. Both lesions had first been noted by the patient 1 year
      previously and for the first 6 months had a similar appearance until the thigh
      mass rapidly increased in size and fungated. Pathology of the large thigh lesion
      showed pilomatrix carcinoma while that of the smaller knee lesion was typical of
      pilomatrixoma. The pilomatrix carcinoma was widely excised and there has been no
      evidence of recurrence or metastasis after 3 years. The clinical course of the
      thigh lesion suggested that pilomatrix carcinoma may arise from a pre-existing
      pilomatrixoma. On review of the literature, pilomatrix carcinoma of the lower
      limb may be more likely to metastasize than those on other sites.

PMID- 11309037
TI  - Giant congenital melanocytic naevus and symptomatic thoracic arachnoid cyst.
AB  - A 43-year-old female with multiple congenital naevi presented with a 5-year
      history of right upper quadrant pain. Magnetic resonance imaging demonstrated a
      large epidural thoracic arachnoid cyst. This case highlights the need to consider
      that the management of patients with giant congenital melanocytic naevus is
      variable depending on the age of the patient, the location of lesions and the
      presence of complications such as neurocutaneous melanosis. The value of magnetic
      resonance scanning as a screening device is discussed.

PMID- 11309038
TI  - Focal facial dermal dysplasia or aplasia cutis congenita: a case with a hair
      collar.
AB  - Aplasia cutis congenita describes localized defects of skin that may have many
      causes. A 6-month-old male presented with bilateral atrophic patches on his
      cheeks distributed along a line from the preauricular area to the angle of the
      mouth. They had been present since birth. He had no other abnormalities
      detectable on examination and no family history of similar lesions. A distinct
      collar of long pale hairs surrounded the lesions, especially the largest one.
      Histology showed changes consistent with aplasia cutis congenita or focal facial
      dermal dysplasia. We propose our patient's lesions may be the result of failure
      of ectodermal fusion over embryological closure lines. This may be a distinct
      subgroup of atrophic facial lesions.

PMID- 11309039
TI  - Bullous pemphigoid induced by cephalexin.
AB  - Two young men developed severe bullous eruptions with a distinctive clinical
      picture of severe flexural involvement and extensive mucosal ulceration. Biopsies
      showed subepidermal bullae and associated inflammation consisted of predominantly
      neutrophils. Both had IgG and C3 staining of the dermal-epidermal junction on
      direct immunofluorescence. Bullous pemphigoid was diagnosed on the basis of
      clinical, histopathological and immunofluorescence findings. Both cases occurred
      after recent ingestion of cephalexin. We believe they represent the first
      reported cases of bullous pemphigoid induced by cephalexin.

PMID- 11309040
TI  - Cutaneous spectrum of coeliac disease.
AB  - Coeliac disease is characterized by gluten intolerance and immunologically
      mediated damage to small intestinal mucosa. Patients classically present with
      gastrointestinal symptoms including chronic diarrhoea, steatorrhoea, weight loss,
      anorexia and abdominal distension. In a substantial proportion of cases however,
      gastrointestinal symptoms are minor or absent, and cutaneous manifestations may
      provide an early clue to diagnosis. Early recognition of coeliac disease, with
      appropriate implementation of a gluten-free diet, may reduce the incidence of
      benign and malignant complications associated with this condition.

PMID- 11309041
TI  - Spindle cell variant of epithelioid sarcoma: an easily misdiagnosed tumour.
AB  - Epithelioid sarcoma is a histologically distinct soft tissue sarcoma of high
      grade malignancy. We report a case of epithelioid sarcoma in a young man who
      presented with multiple nodules over the left forearm, with bony invasion and
      pulmonary metastases. The histological features of the dermal tumour were those
      of a malignant spindle cell tumour with positive cytokeratin and vimentin
      staining and differed from the classical epithelioid sarcoma in its absence of
      typical necrobiotic nodular epithelioid pattern. It was the clinical presentation
      and the histology of the subcutaneous nodules that led to the final diagnosis of
      epithelioid sarcoma. This case illustrates a predominance of spindle cell pattern
      in the dermal tumour of epithelioid sarcoma, which has previously been reported
      as fibroma-like variant of epithelioid sarcoma.

PMID- 11309042
TI  - Lateral longitudinal nail biopsy.
AB  - Lateral longitudinal nail biopsy is the gold standard of incisional nail
      biopsies. It can be obtained under local anaesthetic and requires normal biopsy
      instruments. Preoperative planning with the patient is important in order that
      they have realistic expectations of the therapeutic outcome and understand how to
      care for the wound in the postoperative period.

PMID- 11309043
TI  - Allergic contact dermatitis from ciclopirox olamine.
AB  - A 50-year-old man with interdigital tinea pedis developed an allergic dermatitis
      spreading from the toes to the lower shins. Patch tests were strongly positive to
      ciclopirox olamine 1% pet. Sensitization to this topical antifungal agent has
      rarely been reported in the literature.

PMID- 11309044
TI  - Otolaryngology and the new undergraduate medical curriculum.

PMID- 11309045
TI  - Review of management of drooling problems in neurologically impaired children: a
      review of methods and results over 6 years at Chailey Heritage Clinical Services.
AB  - Drooling can be a difficult problem for a child to endure, both physically and
      socially, especially if they are also having to cope with physical disabilities.
      Chailey Heritage Clinical Services and associated School look after a large
      number of severely physically disabled children and adolescents. This paper
      reviews the management strategy of the multidisciplinary oral-motor clinic at
      Chailey Heritage Clinical Services, and reviews the results of children treated
      between 1990 and 1996. The management ranges from oral-motor skills training
      through palatal training appliances to surgery. Seventy-eight children, ranging
      from 3 to 17 years, were treated and there were complete records for 73. Eighteen
      per cent responded to oral skills training alone. Thirty per cent of children had
      good results with a palatal training appliance and did not need any further
      intervention. Forty-seven per cent of patients underwent some form of surgery to
      control their drooling. Only 8% of children were treated with medication.

PMID- 11309046
TI  - The aetiology of nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma is a disease with a remarkable racial and geographical
      distribution. In most parts of the world it is a rare condition and in only a
      handful of places does this low risk profile alter. These include the Southern
      Chinese, Eskimos and other Arctic natives, inhabitants of South-East Asia and
      also the populations of North Africa and Kuwait.

PMID- 11309047
TI  - Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome):
      otorhinolaryngological manifestations.
AB  - Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder
      affecting blood vessels of the skin, mucous membrane and viscera. The
      otorhinolaryngologist is the commonest clinician involved in management as
      epistaxis occurs in 93% of the patients. As marked advances have recently been
      made regarding the pathogenesis and management of the condition, the
      otorhinolaryngological perspective is reviewed.

PMID- 11309048
TI  - First results of the VoiceMaster prosthesis in three centres in the Netherlands.
AB  - The VoiceMaster indwelling voice prosthesis was designed and developed for use in
      laryngectomized patients. The VoiceMaster pre-production model (0-series), tested
      during 1997 and 1998, proved to be a safe and valid concept. After the refining
      of a few technical details the currently available VoiceMaster device was
      introduced in June 1998. The preliminary results obtained with the device were
      encouraging and led to a multicentre study. The average device life span varies
      between the participating clinics, ranging up to 4.8 months. As there still are
      devices in situ, the average life span is still increasing. Factors such as stoma
      size and fistula position influence the insertion of the device and should be
      considered before VoiceMaster insertion. The general experience with the
      VoiceMaster prosthesis has proven it to be a worthwhile new device in prosthetic
      voice rehabilitation in laryngectomized patients.

PMID- 11309049
TI  - Anticipated absence from work ('sick leave') following routine ENT surgery: are
      we giving the correct advice? A postal questionnaire survey.
AB  - In the UK patients who undergo common ear, nose and throat (ENT) operations, and
      are employed, are advised to take 2 weeks sick leave before returning to their
      employment. A retrospective postal questionnaire survey (of adult patients who
      had undergone four common specific ENT operations) was conducted, to validate
      whether this preoperative advice given, was appropriate, and to attempt to assess
      the patient factors, which influenced the amount of postoperative absence from
      work. Among 218 questionnaires sent, 156 (71.6%) responses were returned and 132
      (60.6%) were used. Analysis of the data for absence from work, showed that 58.3%
      had taken <or= 2 weeks and 41.7% had taken > 2 weeks. The majority of patients
      (70.5%) stated that 2 weeks absence following their surgery was appropriate,
      whereas 5.3% reported that the period was excessive and 24.2% felt that it was
      inadequate. Postoperative pain (30.3%), infection (30.3%), bleeding (7.6%) and
      other causes (15.2%) were reported as the reasons for the delay to return to
      work. Nearly 31% of men and 55% of women had taken > 2 weeks of sick leave. In
      conclusion, the current practice of advising employed adults to take 2 weeks time
      off work following routine ENT surgery is appropriate. However, nearly 42% had
      taken > 2 weeks to return to their employment. Patients who underwent
      tonsillectomy and laser palatoplasty in general, required more time to recuperate
      prior to returning to work, when compared to those who had undergone septoplasty
      and functional endoscopic sinus surgery (FESS). Postoperative pain and infection
      were reported to be the main reasons for the delay in returning to work. Men, and
      self-employed patients returned to work earlier than women and other employed
      groups.

PMID- 11309050
TI  - Expression of MUC1 and MUC2 glycoproteins in laryngeal cancer.
AB  - The aim of this study was to examine the expression of MUC1 and MUC2
      glycoproteins in laryngeal cancer and to determine if mucin expression is related
      to prognosis. The study included laryngeal specimens from 57 patients comprising
      of 36 laryngeal carcinomas and 21 normal controls. High MUC1 expression was found
      in both carcinomas and normal control groups (P = 0.689, Fisher's exact test).
      High levels of MUC2 expression were only detected in carcinomas versus controls
      (P = 0.009, Fisher's exact test). Using multivariate analysis neither MUC1 nor
      MUC2 expression significantly related to survival. MUC1 expression however, did
      correlate with T stage. Advanced T stage was associated with prognosis (P =
      0.001).

PMID- 11309051
TI  - Pattern of ambulatory pharyngo-oesophageal motility and pH-metry in healthy
      volunteers.
AB  - Oesophago-pharyngeal reflux is widely accepted as an aetiological factor in many
      laryngeal and lower respiratory tract diseases. This study aims to establish
      normal reference ranges for pharyngo-oesophageal pH and pressure. Twenty-five
      asymptomatic healthy volunteers underwent ambulatory pharyngo-oesophageal
      pressure and pH-metry. Acid exposure times were very low. Only one subject showed
      any evidence of oesophago-pharyngeal reflux during recumbency. Two distinct upper
      oesophageal sphincter pressure patterns were observed during recumbency-one with
      episodic dry swallows and moderate tonic pressures, the other with almost
      complete manometric quiescence. Negative results, i.e. the exclusion of abnormal
      cervical reflux, appear to be more achievable than quantifiable positive results,
      but this is not absolutely clear from our results. Categorisation of an
      individual as having abnormal upper pH-metry requires use of a synchronous
      pharyngeal probe. pH-metry is likely to be of value in establishing the role of
      reflux in relation to laryngeal or respiratory disease.

PMID- 11309052
TI  - Middle cranial fossa approach for the repair of spontaneous cerebrospinal fluid
      otorrhoea using autologous bone pate.
AB  - Tegmen plate defects causing cerebrospinal fluid (CSF) leaks and brain hernias
      have conventionally been repaired using soft tissue grafts by a transmastoid
      approach. A review of the literature reveals that the results of transmastoid
      repairs have been less than satisfactory. We present here four patients with
      spontaneous CSF otorrhoea who had tegmen defects repaired using the middle
      cranial fossa approach. An autologous bone pate slab mixed with fibrin glue with
      additional temporalis fascia reinforcement was used for the repairs. All four
      patients had uneventful postoperative periods and have had no subsequent CSF leak
      (follow-up range: 1-3 years). We believe that the middle cranial fossa approach
      is more effective than the transmastoid approach for the repair of CSF leaks and
      brain hernias through tegmen plate defects. An important additional benefit is
      hearing preservation. We also recommend the use of bone pate along with soft
      tissue for the repair in order to achieve a secure seal. Bone pate can
      effectively seal multiple defects in the tegmen plate without any risk of
      migration.

PMID- 11309053
TI  - Trends in turbinate surgery literature: a 35-year review.
AB  - A MEDLINE search was used to identify articles involving all forms of turbinate
      surgery over a 35-year period. Five hundred and sixty-one papers were identified.
      Of these, 283 specifically detailed turbinate surgery. These demonstrated a
      marked increase in the number of papers detailing endoscopic and laser turbinate
      surgery in the last 5 years. No randomised controlled studies were identified
      describing inferior turbinate surgery for nasal obstruction or middle turbinate
      surgery for any cause. The evidence supporting the efficacy of these procedures
      remains debatable. Research in this field appears to be driven by technological
      advancement rather than by establishment of patient benefit. Properly conducted
      randomised controlled trials are required to establish whether there is a long
      term patient benefit from these commonly performed operations.

PMID- 11309054
TI  - The clinicopathological significance of bcl-2 expression in the surgical
      treatment of laryngeal carcinoma.
AB  - Bcl-2 expression was studied by immunohistochemistry on laryngectomy specimens
      from 176 patients. Of the 176 tumours, 11% had positive bcl-2 staining. Bcl-2
      expression was significantly correlated with tumour grade: 5% of well
      differentiated tumours, 12% of moderately-differentiated tumours and 23% of
      poorly-differentiated tumours had positive expression of bcl-2. Nodal metastases
      were also found to be significantly related to bcl-2 expression: 36% of nodal
      metastases for negative bcl-2 expression compared with 70% for positive
      expression. The risk of nodal metastases increased significantly with the
      presence of bcl-2 expression, moderate or poor differentiation and supraglottic
      involvement. The risk of nodal metastases increased significantly with the
      presence of increasing numbers of risk factors: 11% without risk factor, 21% with
      one risk factor, 49% with two risk factors and 77% with three risk factors. Bcl-2
      expression in laryngeal carcinoma is significantly correlated with tumour grade
      and nodal metastases. It has added prognostic value for nodal metastases together
      with tumour grade and site of tumour involvement.

PMID- 11309055
TI  - Pleomorphic adenomas of the major salivary glands: a study of the capsular form
      in relation to surgical management.
AB  - This was a retrospective study of 126 primary pleomorphic adenomas to correlate
      capsular characteristics with tumour histopathology in relation to current
      surgical debate (parotidectomy versus local excision). Capsular thickness was
      measured by micrometry and tumours classified into subtypes (1-4). Evidence of
      fine needle aspiration damage (needle tracks, infarction) was sought. Minimal
      changes were seen in eight tumours. Tumour growth features (bosselations,
      enveloping) were present in 57% and 33%, respectively, also microinvasion (42%)
      and tumour 'buds' (12%). Parotid lesions possessed thicker capsules than
      submandibular tumours. There was little correlation between capsular thickness
      and cellular structure. The significant exception was large (> 25 mm)
      hypocellular parotid tumours which had thinner capsules and could be vulnerable
      to operative rupture. In 110 standard operations (parotidectomy, submandibular
      gland excision), capsular exposure was evident in 81%. Field irrigation is
      recommended to lessen the risk of tumour seeding. This study reaffirms many
      elements of capsular weakness and suggests that parotidectomy is the operation of
      choice.

PMID- 11309056
TI  - Outcomes of submandibular duct re-implantation for sialorrhoea.
AB  - Drooling is an important factor affecting the quality of lives of neurologically
      impaired children, and surgery often has to be performed. Submandibular duct
      relocation is a relatively simple procedure with a low complication rate, and has
      been carried out on 37 patients at the Sheffield Children's Hospital between 1986
      and 1998. To determine the short-term and long-term outcome of this procedure, a
      questionnaire was sent to the parents/wards of the patients. Feedback was also
      obtained on complications, parents'/carers' perceptions and main concerns about
      the operation, particularly in those cases which did not improve. Both short-term
      (82.4%) and long-term (76.5%) control rates were high, and there were few
      complications, none of which had any long-term adverse effects. The most
      significant area of parental/carer dissatisfaction and concern in 'failed' cases
      was 'pain', and it was felt that proper preoperative counselling about analgesia
      and chances of failure is very important. We conclude that this is a safe, highly
      successful procedure which significantly improves the quality of lives of the
      majority of drooling children.

PMID- 11309057
TI  - Risk factors for persistence of bilateral otitis media with effusion.
AB  - Otitis media with effusion (OME) is a common, episodic condition in childhood.
      The subset that has persistent bilateral OME is important to identify so that
      their management can be targeted. Most guidelines suggest a watchful-waiting
      period before a decision is made on the appropriateness of surgical intervention.
      In the UK this usually takes place in a specialist setting (otorhinolaryngology)
      over a period of 12 weeks. A cohort of children (n = 639), between the ages of
      3.25 and 6.75 years with bilateral OME that had no previous ear or throat
      surgery, was followed up over 12 weeks during the recruitment phase of a multi
      centre, randomised controlled study. This allowed multiple factors for
      persistence to be assessed. The overall spontaneous resolution rate in this
      cohort was between 26% and 65%, depending on the audiometric cut-off by which a
      persisting condition was defined. Three significant risk factors-time of year
      when first seen (July to December); hearing level (>or= 30 dB HL in the better
      ear); and a route of referral that included prior audiometry--were identified in
      the multivariate analysis for persistent OME both in isolation and when
      accompanied by each of three audiometric cut-offs (>or= 15, >or= 20 and >or= 25dB
      HL). In this age group, parental report of duration of OME, history of acute
      otitis media, parental smoking and pars tensa retractions were not significant
      factors for persistence. These risk factors in combination can increase the odds
      ratio of persistence more than sixfold. However, the proportion persisting is
      insufficient to bypass a period of watchful waiting, except perhaps in extreme
      combinations which apply to less than 7% of the cohort.

PMID- 11309058
TI  - Inhibition of Escherichia coli respiratory enzymes by the lactoperoxidase
      hydrogen peroxide-thiocyanate antimicrobial system.
AB  - AIMS: The lactoperoxidase-hydrogen peroxide-thiocyanate antimicrobial system
      (LPAS) is known to inhibit bacterial respiration. In the present study, several
      respiratory enzymes of Escherichia coli were compared in terms of their
      susceptibility to the LPAS. METHODS AND RESULTS: Exposure of E. coli to the LPAS,
      upon which 99.6% of the bacteria were killed, resulted in the following
      percentage of inactivation of substrate-specific membrane oxidases: succinate
      (94.2%) > NADH (84.6%) > glycerol-3-phosphate (67.8%) > DL-lactate (64.1%). With
      the same treatment, substrate-specific membrane dehydrogenases were inactivated
      as follows: succinate (99.1%) > DL-lactate (53.8%) > glycerol-3-phosphate (45.0%)
      > NADH (36.8%). Terminal oxidase, however, measured using a ubiquinone analogue
      (2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone) after reduction, was only 21.4%
      inactivated by the LPAS. CONCLUSION: These data suggest that dehydrogenases are
      the primary targets of the LPAS in the respiratory chain of E. coli. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study has determined for the first time the primary
      targets of LPAS in the bacterial respiratory chain.

PMID- 11309059
TI  - Antimicrobial properties of phenolic compounds from berries.
AB  - AIMS: To investigate the antimicrobial properties of phenolic compounds present
      in Finnish berries against probiotic bacteria and other intestinal bacteria,
      including pathogenic species. METHODS AND RESULTS: Antimicrobial activity of pure
      phenolic compounds representing flavonoids and phenolic acids, and eight extracts
      from common Finnish berries, was measured against selected Gram-positive and Gram
      negative bacterial species, including probiotic bacteria and the intestinal
      pathogen Salmonella. Antimicrobial activity was screened by an agar diffusion
      method and bacterial growth was measured in liquid culture as a more accurate
      assay. Myricetin inhibited the growth of all lactic acid bacteria derived from
      the human gastrointestinal tract flora but it did not affect the Salmonella
      strain. In general, berry extracts inhibited the growth of Gram-negative but not
      Gram-positive bacteria. These variations may reflect differences in cell surface
      structures between Gram-negative and Gram-positive bacteria. Cloudberry,
      raspberry and strawberry extracts were strong inhibitors of Salmonella. Sea
      buckthorn berry and blackcurrant showed the least activity against Gram-negative
      bacteria. CONCLUSION: Different bacterial species exhibit different sensitivities
      towards phenolics. SIGNIFICANCE AND IMPACT OF THE STUDY: These properties can be
      utilized in functional food development and in food preservative purposes.

PMID- 11309060
TI  - Nutritional requirements and simplified cultivation medium to study growth and
      energetics of a sourdough lactic acid bacterium Lactobacillus fermentum Ogi E1
      during heterolactic fermentation of starch.
AB  - AIMS: Nutritional requirements of Lactobacillus fermentum Ogi E1 were studied in
      order to define a simplified fermentation medium. METHODS AND RESULTS: When grown
      with MRS-medium in 2l bioreactors, a biphasic pattern of growth and metabolite
      production was observed. Study of nutritional requirements resulted in a
      simplified medium (SYAM) that allowed, under anaerobiosis, similar results to be
      obtained as in MRS medium, but without biphasic fermentation kinetics. The best
      substrates for both growth and amylase production were starch and maltose.
      Although melibiose, raffinose, fructose, sucrose and glucose also supported
      growth, lower amylase activity was observed. CONCLUSION: The physiology of the
      strain can be investigated with SYAM medium, using either starch or maltose as
      substrate. The strain also presented potential for alpha-galactoside
      fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus fermentum was
      one of the dominant bacteria of African maize dough fermentations. Amylolytic
      strains with activity against other compounds (i.e. raffinose) suggested a
      potential to be used as starter for cereal fermentation.

PMID- 11309061
TI  - Antibiotic resistance among Listeria, including Listeria monocytogenes, in retail
      foods.
AB  - AIMS: In the past eight to 10 years, reports of antibiotic resistance in food
      borne isolates in many countries have increased, and this work examined the
      susceptibility of 1001 food isolates of Listeria species. METHODS AND RESULTS:
      Susceptibility/resistance to eight antibiotics was determined using the Bauer
      Kirby disc diffusion assay, and 10.9% of the isolates examined displayed
      resistance to one or more antibiotics. Resistance to one or more antibiotics was
      exhibited in 0.6% of Listeria monocytogenes isolates compared with 19.5% of
      Listeria innocua isolates. Resistance was not observed in Listeria seeligeri or
      Listeria welshimeri. Resistance to tetracycline (6.7%) and penicillin (3.7%) was
      the most frequently observed, and while resistance to one antibiotic was most
      common (9.1%), isolates resistant to two or more antibiotics (1.8%) were also
      observed. CONCLUSION: While resistance to the antibiotics most commonly used to
      treat human listeriosis was not observed in L. monocytogenes, the presence of
      such resistance in other Listeria species raises the possibility of future
      acquisition of resistance by L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The higher level of resistance in L. innocua compared with L.
      monocytogenes suggests that a species-related ability to acquire resistance to
      antibiotics exists.

PMID- 11309062
TI  - The bactericidal effect and chemical reactions of acidified nitrite under
      conditions simulating the stomach.
AB  - AIMS: To examine the hypothesis of non-immune defence mechanisms based on
      nitrite. METHODS AND RESULTS: The acidified media (nutrient broth or citrate
      phosphate buffer) under aerobic conditions with additions of physiological levels
      of nitrite, L-ascorbic acid, iodide and thiocyanate were used to simulate gastric
      juice. The bactericidal effects of acidified nitrite on Escherichia coli and
      lactobacilli were investigated using bacterial plate counts. Conversion of
      acidified nitrite to nitric oxide, nitrogen dioxide and nitrate was also studied.
      Nitrite significantly increased the bactericidal effects on E. coli and
      lactobacilli. The bactericidal effects were enhanced by thiocyanate but not by L
      ascorbic acid and iodide. L-Ascorbic acid and thiocyanate, but not iodide,
      enhanced the decomposition of acidified nitrite in nutrient broth. Acidified
      nitrite was converted to both nitric oxide and nitrate, but a portion of the
      acidified nitrite in nutrient broth may have been converted to other unidentified
      nitrogen compounds. Nitrogen dioxide was not detected in any of the samples.
      CONCLUSION: The bactericidal effects of nitrite appeared to be primarily related
      to nitrous acid, and possibly to other unidentified nitrogenous metabolites, but
      not to nitric oxide and nitrogen dioxide. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The potential role of nitrite as an antimicrobial substance in the stomach may be
      of some importance in the ecology of the gastrointestinal tract and in host
      physiology.

PMID- 11309063
TI  - Characterization and growth of Bacillus spp. in heat-treated cream with and
      without nisin.
AB  - AIMS: To study the germination and growth of both inoculated and naturally
      occurring Bacillus strains in heat-treated cream with and without nisin. METHODS
      AND RESULTS: In heat-treated cream (90 degrees C for 15 min) stored at 8 degrees
      C, growth was dominated by naturally occurring Bacillus strains such as Bacillus
      pumilus and B. licheniformis. Only six of the 52 isolated strains were B.
      cereus/thuringiensis. All of the B. cereus strains, but none of the other
      strains, produced enterotoxin when tested with the TECRA and reverse passive
      latex agglutination kits. Bacterial growth during storage of the cream at 8 or 10
      degrees C was completely inhibited by low concentrations of nisin. CONCLUSION:
      The high number of Bacillus strains surviving the heat treatment represent a risk
      for heat-treated food that contains cream. The safety of the cream, for instance
      in "ready-to-eat" products, can be improved by the addition of low concentrations
      of nisin. SIGNIFICANCE AND IMPACT OF THE STUDY: Spores of several Bacillus
      species may survive heat treatment of cream, but low concentration of nisin with
      inhibit germination and growth.

PMID- 11309065
TI  - Development of a monoclonal sandwich ELISA for the detection of animal and human
      Escherichia coli O157 strains.
AB  - AIMS: Production of a monoclonal antibody (MAb) to Escherichia coli O157 to
      develop a rapid test using a sandwich ELISA (sELISA) format. METHODS AND RESULTS:
      A MAb (7A6) was developed to the long-chain lipopolysaccharide of E. coli O157. A
      sELISA developed with the MAb reacted with 28 bovine and seven human
      enterohaemorrhagic E. coli (EHEC) O157 strains and also with two enterotoxigenic
      E. coli O157 strains. Cross-reaction to a rabbit diarrhoeal E.coli O15,
      Citrobacter freundii, Salmonella urbana and Vibrio cholerae O1 Inaba was
      detected. CONCLUSION: A MAb-based sELISA to detect E. coli O157 was produced. Its
      application to field samples is required to fully determine its prospective use
      for the detection of EHEC O157, to evaluate the non-specific interference of the
      cross-reacting strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay produced
      is not wholly specific to EHEC O157, but has the potential to be used as a rapid
      method for screening large numbers of samples for E. coli O157.

PMID- 11309064
TI  - Direct polymerase chain reaction detection of ropy Pediococcus damnosus strains
      in wine.
AB  - AIMS: Glucan-producing strains of Pediococcus damnosus are considered as spoilage
      micro-organisms because synthesis of glucan leads to an unacceptable viscosity of
      wine. In this report, we present a polymerase chain reaction (PCR) procedure to
      detect the presence of such strains in wines. METHODS AND RESULTS: We developed a
      direct DNA isolation method from the wine microflora using polyvinylpyrrolidone
      in order to decrease the polyphenolic concentration. The sequence of the plasmid
      involved in glucan production allowed the design of a primer pair usable for a
      specific and sensitive PCR procedure, leading to the amplification of a 563-bp
      fragment. CONCLUSION: The detection limit in wine was 102 cfu ml-1. The detection
      sensitivity could be increased by using a second primer pair in nested PCR
      assays. SIGNIFICANCE AND IMPACT OF THE STUDY: The method proved to be efficient
      for the early and sensitive detection of ropy Ped. damnosus strains during wine
      making. Time-consuming culture and colony isolation steps are no longer needed.

PMID- 11309066
TI  - Activation of clindamycin phosphate by human skin.
AB  - AIMS: To investigate the relative antimicrobial activity of clindamycin phosphate
      (CP) and clindamycin (Cly) and to examine the effect of skin homogenates on the
      activity of CP. METHODS AND RESULTS: Minimum inhibitory concentrations (MIC) were
      determined against dermally relevant organisms and bactericidal activity was
      studied using time-kill methodology. The effect of skin homogenates on the
      antimicrobial activity of CP was studied by well-diffusion assay. The MIC of Cly
      was substantially lower than that of CP in all susceptible organisms. Clindamycin
      also showed greater bactericidal activity (rate of kill) than CP. Phosphatases in
      skin homogenates activated CP at pH 4-8 with a maximal activation at pH 4.
      CONCLUSION: Phosphatases within the skin have been shown to convert CP to the
      more potent form Cly. SIGNIFICANCE AND IMPACT OF THE STUDY: Conversion to Cly is
      a major determinant of antimicrobial activity in the skin layers following
      topical application of CP.

PMID- 11309067
TI  - Thermal resistance of wild-type and antibiotic-resistant Listeria monocytogenes
      in meat and potato substrates.
AB  - AIMS: This study aimed to elucidate the relationship, if any, between the
      acquisition/possession of antibiotic resistance in strains of Listeria
      monocytogenes and the resistance of such strains to heat stress. METHODS AND
      RESULTS: D-values calculated using a linear survival model were used to compare
      the heat resistance of two wild-type (WT) and two antibiotic (streptomycin)
      resistant (AR) mutant strains of L. monocytogenes measured in minced beef and
      potato substrates at 55 degrees C, with and without prior heat shock at 48
      degrees C. In both minced beef and potato, no significant differences (P < 0.05)
      between D-values of AR and WT strains were noted. Heat shock did not
      significantly increase D-values of WT or AR strains in minced beef, while in
      potato slices, D-values in almost all cases were significantly higher in samples
      which had received heat-shock treatment. In minced beef, the use of a non
      selective/overlay recovery medium did not result in higher D-values for any
      strains, while in potato, significantly higher (P < 0.05) D-values were obtained
      in most cases. CONCLUSION: The presence or absence of antibiotic resistance genes
      did not modulate the heat resistance of the strains examined in this study.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated that heat shock, and
      the type of media used to determine bacterial numbers during heat processing, can
      significantly affect the D-values obtained.

PMID- 11309068
TI  - The effect of temperature on the ensiling process of corn and wheat.
AB  - AIMS: The purpose of this work was to study the effect of temperature on the
      ensiling process and aerobic stability of corn and wheat silages. METHODS AND
      RESULTS: The crops were ensiled in 1.5 l anaerobic jars, with and without an
      inoculant, at room or elevated temperatures (37-41 degrees C). After two months
      of ensiling, the silages were subjected to an aerobic stability test at room and
      elevated (33 degrees C) temperature. The results indicate that ensiling at
      elevated temperatures resulted in higher pH values, less lactic acid and higher
      losses. The silages which were stored at elevated temperatures were more
      susceptible to aerobic spoilage than those stored at room temperature, especially
      when the test was performed at elevated temperature. CONCLUSION: High
      temperatures are detrimental to both the ensiling process and the aerobic
      stability of silages. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of the
      current study suggest that in a warm climate, special care should be taken during
      silage making and storage in order to avoid heating as much as possible. In
      addition, in a warm climate, silages are more susceptible to aerobic
      deterioration and therefore, special care should be taken during unloading.

PMID- 11309069
TI  - Survival of biocontrol Pseudomonas fluorescens CHA0 in lysimeter effluent water
      depends on time of the year and soil type.
AB  - AIMS: To assess the effects of soil type and time of the year on survival of the
      biocontrol inoculant Pseudomonas fluorescens CHA0 under aerobic conditions in
      lysimeter effluent water. METHODS AND RESULTS: Effluent water was collected at
      different times from large outdoor lysimeters (2.5 m deep), which contained a
      well-drained or a poorly-drained cambisol, and inoculated with CHA0. The
      inoculant was monitored for 175 d by colony counts, total immunofluorescence cell
      counts and Kogure's viable cell counts. Cell numbers obtained with the three
      methods were similar. The inoculant declined exponentially in time and its
      population level varied considerably depending on the time of the year at which
      effluent water had been collected and soil type in the lysimeter. Positive
      correlations were found between the number of resident culturable aerobic
      bacteria and subsequent survival of the inoculant. CONCLUSION: The fluctuations
      of inoculant survival patterns correlated with differences in biological
      properties of lysimeter water that were related to soil type and time of the
      year. SIGNIFICANCE AND IMPACT OF THE STUDY: Results suggest that predictability
      of the survival of bacterial soil inoculants transported to groundwater level by
      heavy rainfall may be improved by taking into account key biological properties
      of the water.

PMID- 11309070
TI  - Research of quality indices for cold-smoked salmon using a stepwise multiple
      regression of microbiological counts and physico-chemical parameters.
AB  - AIMS: The aim of the study was to assess the relationships between the remaining
      shelf-life (RSL) of cold-smoked salmon and various microbiological and physico
      chemical parameters, using a multivariate data analysis in the form of stepwise
      forward multiple regression. METHODS AND RESULTS: Thirteen batches of French cold
      smoked salmon were analysed weekly during vacuum-packed storage at 5 degrees C
      for their lipid, water, salt, phenol, pH, total volatile basic nitrogen (TVBN)
      and trimethylamine contents, total psychrotrophic count, lactic acid bacteria,
      lactobacilli, B. thermosphacta, Enterobacteriaceae and yeast counts. At the
      sensory rejection time, the flora was dominated by lactobacilli,
      lactobacilli/Enterobacteriaceae or Carnobacteria/B. thermosphacta. Shelf-life was
      very variable (1->6 weeks) and was related to the initial Enterobacteriaceae load
      (P < 0.05), depending on hygienic conditions in the smokehouse. High correlations
      existed between the RSL and lactobacilli count (P < 0.01), yeast count (P < 0.05)
      and TVBN concentration (P < 0.01). A polynomial fitting the RSL as a function of
      those three factors was proposed (R(2) = 0.80). Assuming that lactobacilli count
      could not exceed 109 cfu g-1, a minimum of 36 mg-N 100 g-1 was necessary for a
      product to be rejected, with a yeast count of 104 cfu g-1. CONCLUSION: Estimation
      of cold-smoked salmon quality is possible by measuring three parameters:
      lactobacilli and yeast counts and TVBN concentration. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The technical content is important for the smoked salmon industry and
      for development of quality standards for cold-smoked salmon.

PMID- 11309071
TI  - Development and use of a new medium to detect yeasts of the genera
      Dekkera/Brettanomyces.
AB  - AIMS: The objectives of this work were to develop a selective and/or differential
      medium able to efficiently recover Dekkera/Brettanomyces sp. from wine-related
      environments and to determine the relationship between these yeasts and the 4
      ethylphenol content in a wide range of wines. METHODS AND RESULTS: The
      selectivity of the developed medium was provided by the addition of ethanol, as
      single carbon source, and cycloheximide. The inclusion of bromocresol green
      evidenced acid-producing strains. The inclusion of p-coumaric acid, substrate for
      the production of 4-ethylphenol, enabled the differentiation by smell of
      Dekkera/Brettanomyces sp. from all other yeast species growing in the medium. The
      medium was used either by plating after membrane filtration or by the Most
      Probable Number (MPN) technique. In 29 white and 88 red randomly collected wines,
      these yeasts were found only in red wines at levels up to 2500 MPN ml-1, but
      constituted less than 1% of the total microbial flora. In red wines, 84% showed
      detectable amounts of 4-ethylphenol up to 4430 microg l-1 while 28% of the white
      wines showed detectable levels up to 403 microg l-1. CONCLUSION: The use of the
      medium proposed in this work evidenced the presence of low relative populations
      of Dekkera/Brettanomyces sp. even in wines contaminated by fast-growing yeasts
      and moulds. SIGNIFICANCE AND IMPACT OF THE STUDY: Further ecological studies on
      Dekkera/Brettanomyces sp. should take into account the use of highly specific
      culture media in order to establish their true occurrence in nature.

PMID- 11309072
TI  - Spatial and temporal distribution of non-starter lactic acid bacteria in Cheddar
      cheese.
AB  - AIMS: The aim of this work was to investigate the spatial and temporal
      distribution of species and strains of non-starter lactic acid bacteria (NSLAB)
      within Cheddar cheese. METHODS AND RESULTS: Randomly amplified polymorphic DNA
      was used to identify and track the principle species and strain groups of NSLAB
      present. The same strains dominated each location examined within a cheese at any
      particular time point. Temporal change in species and strains of NSLAB during
      ripening was observed. A mixture of Lactobacillus paracasei, Lact. plantarum,
      Lact. rhamnosus and unidentified strains was found up to 6 weeks of maturation,
      thereafter only Lact. paracasei strains were isolated. CONCLUSION: Little
      variation in the spatial distribution of NSLAB strains occurs within Cheddar
      cheese; however, temporal changes in the species and strains were observed during
      ripening. SIGNIFICANCE AND IMPACT OF THE STUDY: The complex changes in the
      composition of the NSLAB community of Cheddar cheese may be the source of the
      variation in flavour that is seen in commercial practice.

PMID- 11309073
TI  - Biocatalytic potential of Fusarium globulosum lipase in selective
      acetylation/deacetylation reactions and in ester synthesis.
AB  - AIMS: The present study was carried out to assess the potential of Fusarium
      globulosum lipase (FGL) for chemoselective and regioselective biotransformations
      for the synthesis of industrially important organic compounds. METHODS AND
      RESULTS: Different acetylation/deacetylation reactions and ester synthesis
      reactions were carried out in organic media. Fusarium globulosum lipase showed
      exclusive selectivity for the acetylation of the alcoholic hydroxyl group over
      the phenolic hydroxyl group of the hydroxymethylated phenols and aryl alkyl
      ketones. This also led to the enantiomeric resolution of the aryl alkyl ketone.
      In contrast, the lipase showed reversed selectivity in deacetylation where it
      preferred the phenolic acetoxy group over the alcoholic acetoxy moiety of the
      peracetates of hydroxymethylated compounds. The enzyme also exhibited strict
      regioselection for deacetylation at the para position of the peracetate of an
      aryl alkyl ketone. In addition, the lipase also synthesized a variety of
      industrially important fatty acid esters of sugars, sugar alcohols, alcohols and
      ascorbic acid with high preference for middle-chain fatty acids. CONCLUSION:
      Fusarium globulosum lipase shows versatile catalytic potential in terms of chemo
      , enantio- and regioselectivity and fatty acid specificity in carrying out a
      variety of industrially important biotransformations. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The biocatalytic potential of FGL can thus be utilized for the
      synthesis and modification of different types of polyphenolic compounds and
      esters. These compounds find widespread uses as surfactants, bioactive analogues,
      antioxidants and flavour components in the food, detergent, pharmaceutical and
      cosmetic industries.

PMID- 11309074
TI  - Rapid detection of Listeria monocytogenes in ham samples using immunomagnetic
      separation followed by polymerase chain reaction.
AB  - AIMS: To develop a 24-h system for the detection of Listeria monocytogenes in
      ham. METHODS AND RESULTS: An immunomagnetic separation (IMS) of bacteria directly
      from ham followed by extraction of DNA and detection using a new multiplex
      polymerase chain reaction (PCR) was used. The PCR method used one primer pair
      targeted at the listeriolysin O gene of L. monocytogenes and the other pair for a
      region of the 23S rRNA genes of Listeria, giving products of 706 and 239 bp,
      respectively. The combined IMS/PCR was calculated to be capable of detecting as
      few as 1.1 L. monocytogenes cells g-1 in a 25-g ham sample. CONCLUSION: The
      process produced acceptable results, but the IMS step is the main barrier to
      further improvement of sensitivity. The DNA isolation was the most time-consuming
      step in the process. SIGNIFICANCE AND IMPACT OF THE STUDY: A 24-h test for the
      presence of L. monocytogenes will be useful to the food industry and
      significantly assist in the timely investigation of outbreaks.

PMID- 11309075
TI  - Bacillomycin D: an iturin with antifungal activity against Aspergillus flavus.
AB  - AIMS: In a search for an antifungal peptide with a high activity against
      Aspergillus flavus, Bacillus subtilis AU195 was selected from a collection of
      isolates with antagonistic activity against A. flavus. METHODS AND RESULTS: To
      identify the antifungal peptides, a protein purification scheme was developed
      based on the detection of the antifungal activity in purified fractions against
      A. flavus. Two lipopeptides were purified with anion exchange and gel filtration
      chromatography. Their masses were determined to be 1045 and 1059 m/z with mass
      spectrometry, and their peptide moiety was identical to bacillomycin D.
      CONCLUSION: AU195 synthesized a mixture of two antifungal bacillomycin D
      analogues with masses of 1045 and 1059, the 14 mass unit difference representing
      the difference between a C15 and a C16 lipid chain. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Both bacillomycin D analogues were active at the same concentration
      against A. flavus, but the different lipid chain length apparently affected the
      activity of the lipopeptide against other fungi.

PMID- 11309076
TI  - Extraction and detection of baculoviral DNA from lake water, detritus and forest
      litter.
AB  - AIMS: This paper describes a quick, reproducible, sensitive method for
      baculoviral DNA extraction, purification and detection from freshwater and forest
      litter environments. METHODS AND RESULTS: The extraction protocol utilizes
      enzymatic and chemical lysis and physical disruption. To assess the efficiency of
      the extraction and purification protocol, PCR was used to detect a 530 bp DNA
      fragment from the genome of a genetically-modified baculovirus, Choristoneura
      fumiferana NPVegt-/lacZ+. The detection limit of PCR amplification was routinely
      about 4.1 x 102 occlusion bodies (OBs) 450 microl-1 lake water. Template DNA from
      the detritus and forest litter samples required 100-fold dilutions before use in
      PCR reactions. The detection limits for detritus and forest litter samples were
      routinely about 7.41 x 103 and 2.08 x 104 OBs 0.5 g-1 dry weight, respectively.
      CONCLUSION: The DNA extraction and purification methodology is reproducible,
      sensitive and can be used in lieu of, or in conjunction with, insect bioassays.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The DNA extraction and purification
      protocol described in this paper will facilitate risk assessment and ecological
      studies of both wild-type and genetically-modified baculoviruses.

PMID- 11309077
TI  - The isolation and characterization of Campylobacter jejuni subsp. jejuni from
      domestic geese (Anser anser).
AB  - AIMS: The objectives of this study were to determine the presence of thermophilic
      Campylobacter spp. in free range domestic geese, and to characterize isolated
      strains using phenotyping criteria and SDS-PAGE of whole-cell proteins. METHODS
      AND RESULTS: Forty cloacal swabs from two different flocks of domestic geese were
      examined. All Camp. jejuni strains isolated from geese were biotyped using the
      Lior biotyping scheme. Twelve Camp. jejuni isolates were also tested for their
      susceptibility to 17 different antibacterial agents by a disc diffusion METHOD:
      Fourteen of the isolates were also subjected to SDS-PAGE. All of the geese
      examined were found to harbour Camp. jejuni. Six geese carried more than one
      species of Campylobacter. All strains examined were susceptible to various
      antibiotics but resistant to penicillin G and cephalothin. Eleven strains (92%)
      were resistant to sodium cefuroxime, and eight (67%) were resistant to
      cloxacillin, ampicillin and colistin sulphate. Three strains (25%) were resistant
      to tetracycline, and one strain was resistant to sulfamethoxazole/trimethoprim
      and kanamycin. Nine strains were subtyped as Camp. jejuni subsp. jejuni biotype
      II and the remaining ones as biotype I. There were 96% and 100% similarities
      between all the strains examined by SDS-PAGE. CONCLUSION: This study showed that
      Camp. jejuni were common in the intestinal tract of domestic geese. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Geese should be considered as potential reservoirs for
      human and animal campylobacteriosis. The antibiotic resistance data from this
      study also showed that fluoroquinolone resistance, which appears to be a problem
      in poultry isolates in some countries, is not yet a problem in these geese.

PMID- 11309078
TI  - Update on the detection of beta-exotoxin in Bacillus thuringiensis strains by
      HPLC analysis.
AB  - AIMS: The current work aimed to study the presence of beta-exotoxin by high
      performance liquid chromatography (HPLC) in supernatant fluids from final whole
      cultures of the 69 type strains and 13 subtypes of Bacillus thuringiensis
      strains, as well as from some insecticidal strains. METHODS AND RESULTS: Results
      from HPLC and bioassays with Ephestia kuhniella (Lepidoptera Pyralidae) were
      compared. Type I beta-exotoxin was only detected in type strains representing
      serotypes H1, H9 and H10a,10b. Discrepancies between HPLC and bioassays were
      found in H8a,8b and some insecticidal strains, which suggests the occurrence of
      another soluble toxin different from type I beta-exotoxin, possibly type II beta
      exotoxin. CONCLUSION: This study shows the need to use bioassays to determine the
      presence of beta-exotoxin activity. However, HPLC is a fast and sensitive
      technique if only type I beta-exotoxin is to be determined. The occurrence of
      beta-exotoxin in a type strain does not imply production of this metabolite by
      other strains belonging to the same serovar. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These results complete the characterization of type strains belonging to
      the International Entomopathogenic Bacillus Collection (Institut Pasteur, Paris,
      France).

PMID- 11309079
TI  - Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and
      bacterial skin pathogens.
AB  - AIMS: Nitric oxide is generated from sweat nitrite in the acidic environment of
      the skin surface and is thought to contribute to protection against infection.
      This study examined the sensitivity of Trichophyton mentagrophytes, T. rubrum,
      Candida albicans, Streptococcus pyogenes, Staphylococcus aureus and
      Propionibacterium acnes to acidified nitrite. METHODS AND RESULTS: Organisms were
      cultured in varying concentrations of nitrite and pH for different lengths of
      time, before being transferred to recovery medium. With the exception of Strep.
      pyogenes, addition of nitrite increased the antimicrobial activity of acid
      solutions against all organisms tested. The rank order of sensitivity was: C.
      albicans < T. rubrum < T. mentagrophytes < Staph. aureus < P. acnes, with P.
      acnes being most sensitive. CONCLUSION: This work has shown that acidified
      nitrite is microbiocidal to common cutaneous pathogens. The concentrations of
      nitrite required to kill pathogenic fungi and bacteria in in vitro assays were
      higher than the concentrations of nitrite measured in sweat. However, additional
      co-factors in vivo and in sweat may potentiate the effect of acidified nitrite.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Pharmacological preparations of acidified
      nitrite are novel antimicrobial agents. These data suggest skin organisms which
      may be sensitive to this treatment.

PMID- 11309080
TI  - Purification of a thermostable endochitinase from Streptomyces RC1071 isolated
      from a cerrado soil and its antagonism against phytopathogenic fungi.
AB  - AIMS: The chitinolytic activity of an actinomycete, isolated from a tropical
      acidic ferrasol (FAO) under cerrado (savanna) vegetation, is reported. METHODS
      AND RESULTS: Selection of the strain was based on spot inoculation on solid
      colloidal chitin medium. The use of chemotaxonomic, morphological and
      physiological procedures placed it in the Streptomyces genus, but identification
      to species level could not be achieved. A protein with endochitinase activity was
      isolated and purified from the supernatant fluid by concentration, precipitation,
      hydrophobic interaction, gel filtration and adsorption procedures. The molecular
      size of the purified chitinase was estimated by gel filtration to be 70 kDa, and
      its pI was 6.1. The enzyme had temperature and pH optima of 40 degrees C and 8.0,
      respectively, and showed thermal (30-70 degrees C) and pH (4-9) stabilities.
      Antifungal activity of the selected strain was observed following in vitro
      experiments using growing cells, crude extract or the purified endochitinase, and
      by detecting growth inhibition of the tested phytopathogenic fungi. CONCLUSION:
      Strain Streptomyces RC 1071 could not be placed into any known species,
      suggesting a new taxon. The purified endochitinase presented similar molecular
      weight, optimum temperature and pH activity, and stability of other
      endochitinolytic enzymes reported in the literature. In all three in vitro
      experiments performed, inhibition of growth of the phytopathogenic fungi used as
      test organisms was observed. SIGNIFICANCE AND IMPACT OF THE STUDY: Some of the
      endochitinase characteristics such as thermal stability, as well as pH tolerance,
      are very interesting for biotechnological purposes. In addition, due to its
      antifungal activity, Streptomyces RC 1071 seems promising for use in biological
      control.

PMID- 11309081
TI  - Rhizobia of chickpea from southern Portugal: symbiotic efficiency and genetic
      diversity.
AB  - AIMS: In order to evaluate differences between chickpea rhizobial populations
      from three geographical areas in southern Portugal (Beja, Elvas and Evora),
      isolates from the three regions were obtained and analysed. METHODS AND RESULTS:
      The genetic characterization of the isolates was done by plasmid profiles and
      restriction analysis of the nifH gene. Symbiotic efficiency of the isolates was
      also determined. Relationships between geographical origin, symbiotic efficiency
      and molecular characteristics were established. Beja soil revealed a larger
      rhizobia population as well as the presence of some of the isolates with higher
      symbiotic efficiency values. Isolates with a single plasmid showed a
      significantly higher symbiotic efficiency. CONCLUSION: Genetic and phenotypic
      differences were detected between the natural rhizobial populations from the
      three locations. SIGNIFICANCE AND IMPACT OF THE STUDY: The different yield
      potential with cultivars of chickpea usually obtained in the three regions of
      southern Portugal could be due to their different natural rhizobial populations.

PMID- 11309082
TI  - Characterization of polar lipids of oral isolates of Candida, Pichia and
      Saccharomyces by Fast Atom Bombardment Mass Spectrometry (FAB MS).
AB  - AIMS: To characterize fatty acid and phospholipid analogue profiles of oral
      yeasts. METHODS AND RESULTS: Twenty-seven strains of oral yeasts were cultured on
      SDA and lipids of freeze-dried cells were extracted and analysed by FAB MS. The
      most abundant carboxylate anion was m/z 281 (C18 : 1). The most intense
      phospholipid analogue ions were of PE, PG, PA and PI. Pichia etchellsii contained
      molecular species of PG and PE, whereas Saccharomyces cerevisiae had PA, PG and
      PE analogues. Mass spectra revealed that S. cerevisiae and Candida glabrata were
      distinct from one another and from the other species tested. CONCLUSION: Oral
      yeasts largely differ with respect to their polar lipids. It is concluded that
      oral yeast species have distinctive fatty acid and phospholipid analogue anion
      profiles. SIGNIFICANCE AND IMPACT OF THE STUDY: FAB MS provided novel
      chemotaxonomic information.

PMID- 11309083
TI  - On the quantum physical relation between photon tunnelling and near-field optics.
AB  - The standard theory of optical tunnelling based on a mathematical analogy between
      the time-independent one-particle Schrodinger equation describing electron
      tunnelling and the Helmholtz equation for the macroscopic electric field is
      criticized. In a classical perspective photons are related to the dynamics of the
      transverse part of the electromagnetic field, and with the assumption that the
      electrons in a coupled photon-atom system are driven in a linear fashion by the
      field, a rigorous integro-differential equation for the transverse field is
      established. In the near-field zone of matter a transverse self-field exists and
      this may cause the appearance of superluminality in optical tunnelling. In the
      wake of a brief review of the space-time dynamics of free photons, a first
      quantized description of the birth process of a single polychromatic photon in
      the near-field region of an active atom (molecule, mesoscopic particle) is
      presented, and afterwards the link between photon localizability, Einstein
      causality and near-field photon tunnelling is discussed. On the basis of a new
      one-photon quantum theory of near-field scattering from a microscopic (or
      mesoscopic) object, it is shown that photon tunnelling always appears in photon
      atom scattering. A first-order Born approximation cannot capture the phenomenon,
      however. The emergence of the energy wave function of the scattered photon is
      followed in space and time.

PMID- 11309084
TI  - Immaterial tip concept by light confinement.
AB  - It is shown that the combination of TM polarized coherent evanescent light beams
      can lead to (x, y) confined light distributions. Moreover, owing to the
      evanescent nature of the interfering beams, the spatial distribution of the
      square modulus of the electric field does not vary versus the z-distance. Such an
      energy distribution can be used as a virtual tip, allowing the scanning of a
      sample without any mechanical contact with it.

PMID- 11309085
TI  - Optical near fields as photon-matter interacting systems.
AB  - A quantum theoretical formulation of an optical near-field system developed using
      the projection operator method is shown to be applicable to conventional problems
      in the optical near field in a unified way, and also addresses different quantum
      mechanical issues such as atom manipulation and nano-fabrication. To gain a clear
      insight, the effective mass of exciton-polarizations is introduced; this depends
      on the sizes of the probe tip and sample. We calculate the optical near-field
      intensity detected by (a) a probe sphere and (b) tapered probe modelled by two
      spheres. The results show that the size of the probe tip determines the spatial
      resolution, while the contribution of the tapered part causes degradation of the
      signal contrast. A size-resonance effect between the probe and sample is
      predicted. Furthermore, enhancement of the signal intensity is observed at the
      edges of a circular aperture perpendicular to incident polarization. These
      results are consistent with those obtained from different methods. The approach
      employed is shown to be a valuable tool in physical understanding and analysis of
      the near-field optical phenomena as well as experimental situations.

PMID- 11309086
TI  - Superluminal interactions in near-field optics.
AB  - The fact that photons emitted from an electric-dipole active atom cannot be
      spatially localized better than to the near-field zone of the atom is seen as the
      origin of genuine superluminality. By means of a simple model dipole current
      density the general theory is used to demonstrate numerically how superluminality
      enters the near-field dynamics, and how from a measurement one could be tempted
      to believe that superluminal propagation effects occur. Furthermore, it is shown
      how for source-detector distances larger than a pulse length one should be able
      to divide the pulse into two separate parts: one purely superluminal part arising
      solely in the non-local generation process of the field, and another part
      seemingly propagating with superluminal speed. We comment on different velocity
      analyses, and we argue that the only fundamental velocity entering the problem is
      the vacuum velocity of light, which in a measurement would appear as the velocity
      of the trailing edge of the pulse.

PMID- 11309087
TI  - Theoretical study of transient phenomena in near-field optics.
AB  - A time-domain study of the propagation of a light pulse is made by the finite
      difference time-domain method. This method is described briefly and then two
      applications are presented: creation and diffraction of surface plasmons in the
      time-domain, and propagation of a light pulse through two tip models, a
      dielectric one and a metal-coated one. Results on propagation speed of surface
      plasmons, spatio-temporal shape and spectral study of the field emitted by a tip
      are presented.

PMID- 11309088
TI  - Near-field optical addressing of single molecules in coplanar geometry: a
      theoretical study.
AB  - Photonic transfer through elongated optical structures of submicrometre section
      microfabricated at the surface of dielectric or semiconductor samples can be
      enhanced by an appropriate structuring of the local refraction index. We show
      from computerized simulations that both the light localization and the
      spectroscopic properties of such structures can be used to selectively excite, in
      coplanar geometry, individuals molecules located in the near-field.

PMID- 11309089
TI  - Near-field mapping of surface polariton fields.
AB  - Using the general approach to image formation in collection near-field optical
      microscopy, I derive the symmetry relations for the amplitude coupling
      coefficients in the case of a weakly guiding single-mode fibre terminated with a
      probe tip possessing axial symmetry. It is shown that, for the symmetrical
      detection configuration, six elements of the coupling matrix can be expressed by
      using only three independent coupling coefficients. The obtained relations are
      further applied to describe near-field mapping of surface plasmon polariton (SPP)
      fields. I demonstrate that, for the symmetrical detection configuration, the near
      field optical image reflects the intensity distribution of the SPP field
      components parallel to the surface plane, even though the strong perpendicular
      component is also being detected. This conclusion is supported with numerical
      simulations that elucidate the influence of symmetry of the fibre probe on the
      resulting near-field optical image. The near-field optical images simulated for
      scattering systems typical for SPP microoptics and localization are presented. It
      is found that the presence of asymmetry in the detection configuration increases
      the contribution of the perpendicular field component and results in the images
      approaching the corresponding SPP intensity distributions.

PMID- 11309090
TI  - Direct interpretation of near-field optical images.
AB  - The interpretation of the detection process in near-field optical microscopy is
      reviewed on the basis of a discussion about the possibility of establishing
      direct comparisons between experimental images and the solutions of Maxwell
      equations or the electromagnetic local density of states. On the basis of simple
      physical arguments, it is expected that the solutions of Maxwell equations should
      agree with images obtained by collecting mode near-field microscopes, while the
      electromagnetic local density of states should be considered to provide a
      practical interpretation of illumination mode near-field microscopes. We review
      collecting mode near-field microscope images where the conditions to obtain good
      agreement with the solutions of Maxwell equations have indeed been identified. In
      this context of collecting mode near-field microscopes, a fundamentally different
      functionality between dielectric and gold-coated tips has been clearly identified
      experimentally by checking against the solutions of Maxwell equations. It turns
      out that dielectric tips detect a signal proportional to the optical electric
      field intensity, whereas gold-coated tips detect a signal proportional to the
      optical magnetic field intensity. The possible implications of this surprising
      phenomenon are discussed.

PMID- 11309091
TI  - Time-frequency analysis: a tool to discriminate artefacts from near-field optical
      data.
AB  - Near-field optical data are non-stationary, which means that their spectral
      content varies with the position of the tip, due to both the scanning-probe
      recording process and the variations of the optical signal. Therefore time
      frequency representations are potentially powerful tools for local
      characterization as they distribute the energy of the analysed signal over the
      time and frequency variables, and faithfully depict the signal local behaviour.
      In this paper, the time-frequency distributions are shown to be appropriate tools
      to analyse near-field optical data by using it first on simulated data, and
      second on experimental near-field optical images. Within this context, we observe
      that time-frequency analysis allows a possible separation of relevant optical
      signals from artefacts, especially in the usual case where the near-field optical
      signal is lower band than the feedback data.

PMID- 11309092
TI  - Three-dimensional analysis of light propagation through uncoated near-field fibre
      probes.
AB  - The near-field emission from uncoated tapered fibre probes is investigated for
      different probe geometries. The three-dimensional model calculations are based on
      Maxwell's curl equations and describe the propagation of a 10 fs optical pulse
      (lambda = 805 nm) through tapers of different lengths and different diameters of
      the taper exit. The numerical evaluation is done with a finite difference time
      domain code. Two tapers with cone angles of 50 degrees, with taper lengths of 1.5
      microm and 1.0 microm and exit diameters of 100 nm and 520 nm, respectively, are
      considered. We find that without sample the short taper with large exit diameter
      optimizes both light transmission and spatial resolution. In the presence of a
      sample with a high dielectric constant, however, the spatial near-field
      distribution changes drastically for both taper geometries. We find a pronounced
      increase in spatial resolution, down to about 250 nm inside the medium. This
      collimation of the near-field distribution arises from interferences between
      emitted and reflected light from the sample surface and from a collimation effect
      that the field experiences in the high-index semiconductor material. The
      combination of high spatial resolution and transmission and collection
      efficiencies makes such probes interesting for spectroscopic investigations, as
      demonstrated by recent experiments.

PMID- 11309093
TI  - Probe design optimization for a high-resolution scattering-type scanning near
      field optical microscope.
AB  - The scattering-type scanning near-field optical microscope (SNOM) has a probe
      with a sharp tip for use in high resolution imaging. As sharp a tip as possible
      is generally considered ideal for the observations, but actually, a sharp tip
      does not always provide a high resolution SNOM image. We numerically examined the
      scattering property of the SNOM probe by the three dimensional finite difference
      time domain METHOD: In this paper, we show the criterion for the ideal scattering
      probe which satisfies the simple relation between radius and taper angle of the
      tip.

PMID- 11309094
TI  - On the coupling efficiency of metal-coated near-field probes.
AB  - A theory for calculating the optical transmission of nanometric circular
      apertures in a thick and perfectly conducting screen coated upon an optical fibre
      has been developed. The theory is intended for the study of near-field probes and
      differs from other well known theories of radiation transmission through
      subwavelength apertures in the fact that it includes an optical fibre, making
      possible to distinguish which part of energy passing through the aperture is
      effectively coupled in guided modes. In a scanning near-field optical microscope
      tip, only the guided modes will reach the photodetector, and will contribute to
      the final read-out. A numerical calculation for different fibre parameters, to
      show the dependence of the guided transmission coefficient for the guided modes
      of the fibre, is presented. The agreement of the theory with earlier calculations
      where the optical fibre is not included is emphasized.

PMID- 11309095
TI  - Far-field emission of a tapered optical fibre tip: a theoretical analysis.
AB  - The far-field transmission pattern of a tapered optical tip with small aperture
      (radius approximately < 40 nm) is modelled by solving Maxwell's equations in the
      radiation zone with boundary conditions appropriate to the conical geometry. The
      model is able to reproduce the large differences between the S and P
      polarizations observed previously in the emission profile of such a tip
      [Obermuller and Karrai. Appl. Phys. Lett. (1995) 67, 3408].

PMID- 11309096
TI  - Near-field fluorescence imaging of single molecules with a resolution in the
      range of 10 nm.
AB  - We demonstrate fluorescence imaging of single molecules, by near-field scanning
      optical microscopy (NSOM), using the illumination-collection mode of operation,
      with an aperture probe. Fluorescence images of single dye molecules were obtained
      with a spatial resolution of 15 nm, which is smaller than the diameter of the
      aperture (20 nm) of the probe employed. Such super-resolution may be attributable
      to non-radiative energy transfer from the molecules to the coated metal of the
      probe since the resolution obtained in the case of conventional NSOM is limited
      to 30-50 nm due to penetration of light into the metal.

PMID- 11309097
TI  - Probing confined fields with single molecules and vice versa.
AB  - Single dye molecules are used as local probes to map the spatial distribution of
      the squared electric field components in the focus of a high numerical aperture
      lens. Simulated field distributions are quantitatively verified by experimentally
      obtained fluorescence excitation maps. We show that annular illumination can be
      used to engineer the field distribution in the focus at a dielectric/air
      interface such that electric field components in all directions acquire
      comparable magnitudes. The 3D orientation of molecular absorption dipoles can be
      determined by comparing measured to simulated image patterns. The presence of
      longitudinal electric field components in a focus is of particular interest in
      tip-enhanced scanning near-field optical microscopy.

PMID- 11309098
TI  - Near-field effects in single molecule emission.
AB  - We present the first experimental proof of the influence of a nearby nano-sized
      metal object on the angular photon emission by a single molecule. A novel angular
      sensitive detection scheme is implemented in an existing near-field scanning
      optical microscope (NSOM). The positioning accuracy ( approximately 1 nm) of the
      NSOM allows a systematic investigation of the intensity ratio between two
      different half-spaces as a function of the position of the metal-glass interfaces
      of the probe with respect to the single emitter. The observed effects are shown
      to be particularly strong for molecules that are excited mainly below the rims of
      the aperture. An excellent agreement is found between experiments and numerical
      simulations for these molecules. The observed angular redistribution of the
      angular emission of a single molecule could explain the alteration of the
      emission polarization observed for certain molecules in earlier experiments
      (Veerman et al. (1999) J. Microsc. 194, 477-482).

PMID- 11309099
TI  - Imaging of monolayers composed of palmitic acid and lung surfactant protein B.
AB  - Near-field scanning optical microscopy and atomic force microscopy are used to
      probe the sub-micrometre phase structure in palmitic acid monolayers containing
      the 25 peptide amino terminus of lung surfactant protein B (SP-B(1-25)).
      Monolayers deposited onto mica substrates at a surface pressure of 15 mN m-1
      exhibit a two-phase coexistence across a broad range of SP-B(1-25)
      concentrations. Monolayers containing 5 wt.% SP-B(1-25) or less exhibit an
      expanse of liquid condensed phase in which elliptical liquid expanded (LE)
      domains with areas of approximately 25 microm2 coexist. By contrast, monolayers
      containing 20 wt.% SP-B(1-25) exhibit an expanse of liquid expanded phase in
      which circular liquid condensed domains coexist. The phase distribution
      dependence on SP-B(1-25) concentration suggests that the peptide induces disorder
      in the monolayer.

PMID- 11309100
TI  - Mapping the distribution of emissive molecules in human ocular lipofuscin
      granules with near-field scanning optical microscopy.
AB  - Several high resolution imaging techniques are utilized to probe the structure of
      human ocular lipofuscin granules. Atomic force microscopy reveals typical granule
      sizes to be about one micrometre in diameter and hundreds of nanometres in
      height, in agreement with previous electron microscopy results. For issues
      concerning the role of lipofuscin in age-related macular degeneration, recent
      attention has focused on the orange-emitting fluorophore, A2E. Confocal
      microscopy measurements are presented which reveal the presence of a highly
      emissive component in the granules, consistent with the presence of A2E. It is
      shown, however, that the interpretation of these results is complicated by the
      lack of structural details about the particles. To address these issues, near
      field scanning optical microscopy (NSOM) measurements are presented which measure
      both the lipofuscin fluorescence and topography, simultaneously. These
      measurements reveal distinct structure in the fluorescence image which do not
      necessarily correlate with the topography of the granules. Moreover, direct
      comparison between the NSOM fluorescence and topography measurements suggests
      that A2E is not the major component in lipofuscin. These measurements illustrate
      the unique capabilities of NSOM for probing into the microstructure of lipofuscin
      and uncovering new insights into its phototoxicity.

PMID- 11309101
TI  - Sub-wavelength region spectroscopy and local morphology of individual mesoscopic
      quantum systems.
AB  - Results of reflection microscopy and local reflection spectroscopy of J
      aggregates of two pseudoisocyanine dyes in a thin film polymer matrix are
      reported. The individual J-aggregates assemble into fibre-like shapes of large
      structural heterogeneity. Reflectance spectra obtained at different samples,
      different locations on one sample and even at different positions of the same
      aggregate fibre reveal a wide distribution of optical properties. The shapes and
      absolute reflectivities of the spectra are suggested to originate from varying
      strengths of exciton-photon interaction and from the effect of finite thickness
      of the aggregate fibres. Polarization dependence measurements of local
      reflectivities provide orientations of the exciton transition dipole moments at
      572 nm and 540 nm with respect to the orientation of the aggregate fibres.
      Furthermore, modified synthesis of capped semiconductor nanocrystals of CdSe is
      presented. The method yields high quality quantum dots suitable for microscopic
      imaging and spectroscopy.

PMID- 11309102
TI  - Study of energy transfer from excited TPD to Alq in organic electroluminescent
      devices by time-resolved fluorescence spectroscopy using a scanning near-field
      optical atomic force microscope.
AB  - We demonstrate the direct measurement of molecular diffusion at organic/organic
      interfaces of organic electroluminescence devices by use of a scanning near-field
      optical atomic force microscope. Our preliminary study shows that the degradation
      of an electroluminescence device is partly caused by crystallization of the
      organic layers. Because the initial stage of degradation cannot be observed by
      microscopic methods, nanoscale optical properties of the interface in multilayer
      systems are currently receiving a great deal of attention. Defects of organic
      electroluminescence devices were investigated using a scanning near-field optical
      atomic force microscope. This instrument is capable of measuring both a
      topographic and a fluorescence image at the same time. The defect area and other
      areas are clearly observed and time-resolved near-field fluorescence spectra
      demonstrate emission of the different species. These results suggest that defects
      occur at the organic solid interface, and that energy transfer occurs from
      excited TPD, as donor, to Alq, as acceptor.

PMID- 11309103
TI  - Excitation energy transfer of porphyrin in polymer thin films by time-resolved
      scanning near-field optical microspectroscopy.
AB  - Thin films of water-soluble free-base porphyrin, 5,10,15,20-tetraphenyl-21H, 23H
      porphinetetrasulphonic acid (TPPS) mixed with poly(diallyldimethyl ammonium
      chloride) (PDDA) have been prepared by a spin-coating method, in which the
      monomeric species were observed in the spin-coat film, whereas dimer was formed
      in the cast film prepared from TPPS/PDDA solution. Mesoscopic structures and
      dynamics of excitation energy migration and trapping of TPPS/PDDA spin-coat film
      have been analysed by time-resolved scanning near-field optical microspectroscopy
      (SNOM) and atomic force microscope. The observed film structure can be classified
      roughly into two parts: one is a large, flocculated polymer part, and the other
      is a smooth part widely spread around the flocculated polymers. In the smooth
      part, the observed spindle-like structure and circular hills and dips are
      essentially due to PDDA. The ellipsoidal small structures with approximately 2
      microm length and < 1 microm width in the flocculated polymer part show non
      exponential fluorescence decays. The non-exponential dynamics originates from the
      excitation energy migration among TPPS monomers and energy trapping to dimers.
      From the analysis of fluorescence decay curves based on the equation developed by
      Klafter and Blumen, the spectral dimension has been estimated to be approximately
      1.46 for ellipsoidal structures. These results indicate that the distribution of
      the chromophore is inhomogeneous and a fractal-like structure exists even in the
      small domains determined by the resolution of the SNOM tip.

PMID- 11309104
TI  - Combining AFM and FRET for high resolution fluorescence microscopy.
AB  - Here we demonstrate a new microscopic method that combines atomic force
      microscopy (AFM) with fluorescence resonance energy transfer (FRET). This method
      takes advantage of the strong distance dependence in Forster energy transfer
      between dyes with the appropriate donor/acceptor properties to couple an optical
      dimension with conventional AFM. This is achieved by attaching an acceptor dye to
      the end of an AFM tip and exciting a sample bound donor dye through far-field
      illumination. Energy transfer from the excited donor to the tip immobilized
      acceptor dye leads to emission in the red whenever there is sufficient overlap
      between the two dyes. Because of the highly exponential distance dependence in
      this process, only those dyes located at the apex of the AFM tip, nearest the
      sample, interact strongly. This limited and highly specific interaction provides
      a mechanism for obtaining fluorescence contrast with high spatial resolution.
      Initial results in which 400 nm resolution is obtained through this AFM/FRET
      imaging technique are reported. Future modifications in the probe design are
      discussed to further improve both the fluorescence resolution and imaging
      capabilities of this new technique.

PMID- 11309105
TI  - Near-field fluorescence imaging and simultaneous observation of surface
      potentials.
AB  - We present a new detection method to measure simultaneously surface potential and
      fluorescence intensity distributions using a combined scanning near-field optical
      microscope-atomic force microscope (SNOM-AFM). A surface potential image of
      phospholipid monolayers was obtained in non-contact mode using the SNOM-AFM with
      a thin-step etched optical fibre probe. For applying this technique, a
      phospholipid of dipalmitoylphosphatidylethanolamine labelled at the head with a
      nitrobenzoxadiazole group was used as a fluorescent and single component Langmuir
      Blodgett film. It is well known that aggregation of the lipid molecules and their
      fluorescence intensities are very sensitive to its environmental conditions such
      as humidity and temperature. We demonstrated for the first time the near-field
      optical imaging and simultaneous observation of surface potentials with Maxwell
      stress microscopy.

PMID- 11309106
TI  - Morphology, fluorescence properties, and their photothermal changes of
      poly(substituted thiophene) films revealed by near-field fluorescence
      microspectroscopy.
AB  - The morphology and fluorescence spectrum of poly(3-[2-(N
      dodecylcarbamoyloxy)ethyl]thiophene-2,5-diyl) film were examined with spatial
      resolution of 100 nm using near-field fluorescence microspectroscopy.
      Fluorescence spectra observed at protruding domains were blue-shifted compared
      with flat areas, and further blue-shift was observed there more appreciably by
      long-time irradiation via a near-field scanning optical microscope probe. It is
      considered that the polymer chains at the protruding domains take disordered
      conformations, in which conjugated lengths are shorter and further disordering
      can be induced more easily by irradiation compared with those in the flat areas.

PMID- 11309107
TI  - Mesoscopic structures and dynamics of merocyanine J-aggregate studied by time
      resolved fluorescence SNOM.
AB  - Time-resolved fluorescence SNOM is used to probe the mesoscopic structure and
      dynamics of long-chain merocyanine (C18MC) J-aggregates on glass plates prepared
      by spin coating, casting, and casting of water-soluble polymer films. A globular
      structure with an average diameter of approximately 1 microm and a height of
      approximately 50 nm was attributed to the J-aggregate of C18MC in the spin
      coating film. In polymer films, the bandwidth of the absorption of J-aggregate is
      much narrower in polyvinyl alcohol (PVA, approximately 20 nm) than that in
      polyvinyl sulphate (PVS, approximately 60 nm). We have demonstrated that the
      large bandwidth of the spectrum is due to the inhomogeneous distribution of the J
      aggregate. The fluorescence image of the J-aggregate in PVA film was rather
      uniform, whereas non-uniform distribution of the fluorescence was observed in PVS
      film. The fluorescence of C18MC J-aggregate in a small domain of PVA film was a
      single exponential decay with a lifetime as short as 19 ps, which was shorter
      than that in PVS film with a two-exponential decay (average lifetime of
      approximately 25 ps). The fluorescence lifetime of the J-aggregate and its single
      exponential behaviour are considered to be indicators of the uniform distribution
      of the J-aggregate. The non-uniform distribution of the J-aggregate in PVS film
      was interpreted in terms of electrostatic interaction between PVS and
      merocyanine.

PMID- 11309108
TI  - Fluorescence scanning near-field optical microscopy of polyfluorene composites.
AB  - Fluorescence scanning near-field optical microscopy (SNOM) is used to investigate
      binary polyfluorene-based composites of varying composition. The samples
      investigated contain blends of the polymer poly(9,9'-dioctylfluorene
      cobenzothiadiazole), F8BT, with similar polyfluorenes of wider band gap. Images
      acquired from a film containing 50% by weight F8BT exhibit a high degree of
      correlation between the topography and fluorescence, with an F8BT-rich phase
      which protrudes from the surface of the film forming isolated regions with sizes
      from hundreds of nanometres to several micrometres. A film containing 10% by
      weight F8BT also has micrometre-size F8BT-rich regions, but also present are
      small and locally varying proportions of F8BT in the other polyfluorene component
      phase, indicating a hierarchy of phases within this sample. The fluorescence and
      topographic images of a third sample studied, containing 90% by weight F8BT,
      display no correlation, demonstrating that it is not always appropriate to use
      topographic information to determine the phase structure within polymer blends.
      The fluorescence SNOM images acquired from these samples are able to assist our
      understanding of the photovoltaic efficiency of devices fabricated from these
      films, which are governed by the extent of the interfacial area between these two
      constituent polymers.

PMID- 11309109
TI  - Control of the vibration damping through surface functionalization of a shear
      force probe.
AB  - Shear force mapping on thiolipid Langmuir-Blodgett monolayers probed with Al
      coated tips leads to a contrast highly dependent on the monolayer molecular
      organization, which does not correspond to the topographical relief of the
      sample. The use of functionalized surface probes offers the possibility to better
      control the probe-to-sample interaction. In addition, hydrophilic surface probes
      are totally insensitive to alkyl chain arrangements in the monolayer. Hydrophobic
      probes, instead, can be chosen to map shear force on soft samples in liquid
      environment, since their mechanical properties are not influenced by the
      surrounding liquid.

PMID- 11309110
TI  - Spectroscopic scanning near-field optical microscopy with a free electron laser:
      CH2 bond imaging in diamond films.
AB  - Hydrogen chemistry in thin films and biological systems is one of the most
      difficult experimental problems in today's science and technology. We
      successfully tested a novel solution, based on the spectroscopic version of
      scanning near-field optical microscopy (SNOM). The tunable infrared radiation of
      the Vanderbilt free electron laser enabled us to reveal clearly hydrogen
      decorated grain boundaries on nominally hydrogen-free diamond films. The images
      were obtained by SNOM detection of reflected 3.5 microm photons, corresponding to
      the C-H stretch absorption, and reached a lateral resolution of 0.2 microm, well
      below the lambda/2 (lambda = wavelength) limit of classical microscopy.

PMID- 11309111
TI  - Biology of type II secretion.
AB  - The type II secretion pathway or the main terminal branch of the general
      secretion pathway, as it has also been referred to, is widely distributed among
      Proteobacteria, in which it is responsible for the extracellular secretion of
      toxins and hydrolytic enzymes, many of which contribute to pathogenesis in both
      plants and animals. Secretion through this pathway differs from most other
      membrane transport systems, in that its substrates consist of folded proteins.
      The type II secretion apparatus is composed of at least 12 different gene
      products that are thought to form a multiprotein complex, which spans the
      periplasmic compartment and is specifically required for translocation of the
      secreted proteins across the outer membrane. This pathway shares many features
      with the type IV pilus biogenesis system, including the ability to assemble a
      pilus-like structure. This review discusses recent findings on the organization
      of the secretion apparatus and the role of its various components in secretion.
      Different models for pilus-mediated secretion through the gated pore in the outer
      membrane are also presented, as are the possible properties that determine
      whether a protein is recognized and secreted by the type II pathway.

PMID- 11309112
TI  - Type III export: new uses for an old pathway.
AB  - Gram-negative bacteria use type III secretion (TTS) systems to translocate
      proteins into the extracellular environment or directly into eukaryotic cells.
      These complex secretory systems are assembled from over 20 different structural
      proteins, including 10 that have counterparts in the flagellar export pathway.
      Secretion substrates are directed to the TTS machinery via mRNA and/or amino acid
      secretion signals. TTS chaperones bind to select secretion substrates and assist
      in the export process. Recent progress in the understanding of TTS is reviewed.

PMID- 11309114
TI  - Two-partner secretion in Gram-negative bacteria: a thrifty, specific pathway for
      large virulence proteins.
AB  - A collection of large virulence exoproteins, including Ca2+-independent
      cytolysins, an iron acquisition protein and several adhesins, are secreted by the
      two-partner secretion (TPS) pathway in various Gram-negative bacteria. The
      hallmarks of the TPS pathway are the presence of an N-proximal module called the
      'secretion domain' in the exoproteins that we have named the TpsA family, and the
      channel-forming beta-barrel transporter proteins we refer to as the TpsB family.
      The genes for cognate exoprotein and transporter protein are usually organized in
      an operon. Specific secretion signals are present in a highly conserved region of
      the secretion domain of TpsAs. TpsBs probably serve as specific receptors of the
      TpsA secretion signals and as channels for the translocation of the exoproteins
      across the outer membrane. A subfamily of transporters also mediates activation
      of their cognate cytolysins upon secretion. The exoproteins are synthesized as
      precursors with an N-terminal cleavable signal peptide, and a subset of them
      carries an extended signal peptide of unknown function. According to our current
      model, the exoproteins are probably translocated across the cytoplasmic membrane
      in a Sec-dependent fashion, and their signal peptide is probably processed by a
      LepB-type signal peptidase. The N-proximal secretion domain directs the
      exoproteins towards their transporters early, so that translocation across both
      membranes is coupled. The exoproteins transit through the periplasm in an
      extended conformation and fold progressively at the cell surface before
      eventually being released into the extracellular milieu. Several adhesins also
      undergo extensive proteolytic processing upon secretion. The genes of many new
      TpsAs and TpsBs are found in recently sequenced genomes, suggesting that the TPS
      pathway is widespread.

PMID- 11309113
TI  - Type IV secretion: intercellular transfer of macromolecules by systems
      ancestrally related to conjugation machines.
AB  - Bacterial conjugation systems are highly promiscuous macromolecular transfer
      systems that impact human health significantly. In clinical settings, conjugation
      is exceptionally problematic, leading to the rapid dissemination of antibiotic
      resistance genes and other virulence traits among bacterial populations. Recent
      work has shown that several pathogens of plants and mammals - Agrobacterium
      tumefaciens, Bordetella pertussis, Helicobacter pylori and Legionella pneumophila
      - have evolved secretion pathways ancestrally related to conjugation systems for
      the purpose of delivering effector molecules to eukaryotic target cells. Each of
      these systems exports distinct DNA or protein substrates to effect a myriad of
      changes in host cell physiology during infection. Collectively, secretion
      pathways ancestrally related to bacterial conjugation systems are now referred to
      as the type IV secretion family. The list of putative type IV family members is
      increasing rapidly, suggesting that macromolecular transfer by these systems is a
      widespread phenomenon in nature.

PMID- 11309115
TI  - Biogenesis of inner membrane proteins in Escherichia coli.
AB  - For a long time, it was generally assumed that the biogenesis of inner membrane
      proteins in Escherichia coli occurs spontaneously, and that only the
      translocation of large periplasmic domains requires the aid of a protein
      machinery, the Sec translocon. However, evidence obtained in recent years
      indicates that most, if not all, inner membrane proteins require the assistance
      of protein factors to reach their native conformation in the membrane. Here, we
      review and discuss recent advances in our understanding of the biogenesis of
      inner membrane proteins in E. coli.

PMID- 11309116
TI  - Identification of a twin-arginine leader-binding protein.
AB  - The transport and targeting of a number of periplasmic proteins is carried out by
      the Sec-independent Mtt (also referred to as Tat) protein translocase. Proteins
      using this translocase have a distinct twin-arginine-containing leader. We
      hypothesized that specific leader-binding proteins exist to escort proteins to
      the translocase complex. A fusion was constructed with the twin-arginine leader
      from dimethyl sulphoxide (DMSO) reductase, subunit DmsA, to the N-terminus of
      glutathione-S-transferase. This leader fusion was bound to a glutathione affinity
      column through which an Escherichia coli anaerobic cell-free extract was passed.
      Proteins that bound to the leader were then separated and identified by N
      terminal sequencing, which identified DnaK and a protein originating from the
      uncharacterized reading frame ynfI. This gene has been designated dmsD based on
      the findings presented in this paper. DmsD was purified as a His6 fusion and was
      shown to interact with preprotein forms of DmsA and TorA (trimethyl amine N-oxide
      reductase). A strain carrying a dmsD knock-out mutation showed a loss of
      anaerobic growth on glycerol-DMSO medium and reduced growth on glycerol-fumarate
      medium. This work suggests that DmsD is a twin-arginine leader-binding protein.

PMID- 11309117
TI  - Formation of disulphide bonds during secretion of proteins through the
      periplasmic-independent type I pathway.
AB  - In this work, we have investigated whether the bacterial type I secretion
      pathway, which does not have a periplasmic intermediate of the secreted protein,
      allows the formation of disulphide bridges. To this end, the formation of
      disulphide bonds has been studied in an antibody single-chain Fv (scFv) fragment
      secreted by the Escherichia coli haemolysin (Hly) transporter (a paradigm of type
      I secretion). The scFv antibody fragment was used as a disulphide bond and
      protein-folding reporter, as it contains two disulphide bridges that are required
      for its correct folding (i.e. to preserve its antigen-binding activity). We show
      that an scFv-HlyA hybrid secreted by Hly type I transporter (TolC, HlyB, HlyD) is
      accumulated in the extracellular medium with the disulphide bonds correctly
      formed. Neither periplasmic and inner membrane-bound Dsb enzymes (e.g. DsbC,
      DsbG, DsbB and DsbD) nor cytoplasmic thioredoxins (TrxA and TrxC) were required
      for scFv-HlyA oxidation. However, a mutation of the thioredoxin reductase gene
      (trxB), which leads to the cytoplasmic accumulation of the oxidized forms of
      thioredoxins, had a specific inhibitory effect on the Hly-dependent secretion of
      disulphide-containing proteins. These data suggest that premature cytoplasmic
      oxidation of the substrate may interfere with the secretion process. Taken
      together, these results indicate not only that the type I system tolerates
      secretion of disulphide-containing proteins, but also that disulphide bonds are
      specifically formed during the passage of the polypeptide through the export
      conduit.

PMID- 11309118
TI  - A set of ftsZ mutants blocked at different stages of cell division in
      Caulobacter.
AB  - FtsZ is required throughout the cell division process in eubacteria and in
      archaea. We report the isolation of novel mutants of the FtsZ gene in Caulobacter
      crescentus. Clusters of charged amino acids were changed to alanine to minimize
      mutations that affect protein folding. Molecular modelling indicated that all the
      clustered-charged-to-alanine mutations had altered amino acids at the surface of
      the protein. Of 13 such mutants, four were recessive-lethal, three were dominant
      lethal, and six had no discernible phenotype. An FtsZ depletion strain of
      Caulobacter was constructed to analyse the phenotype of the recessive-lethal
      mutations and used to show that they blocked cell division at distinct stages.
      One mutation blocked the initiation of cell division, two mutations blocked cell
      division randomly, and one mutation blocked both early and late stages of cell
      division. The effect of the recessive mutations on the subcellular localization
      of FtsZ was determined. Models to explain the various mutant phenotypes are
      discussed. This is the first set of recessive alleles of ftsZ blocked at
      different stages of cell division.

PMID- 11309119
TI  - The Aspergillus nidulans GATA transcription factor gene areB encodes at least
      three proteins and features three classes of mutation.
AB  - In Aspergillus nidulans, the principal transcription factor regulating nitrogen
      metabolism, AREA, belongs to the GATA family of DNA-binding proteins. In seeking
      additional GATA factors, we have cloned areB, which was originally identified via
      a genetic screen for suppressors of areA loss-of-function mutations. Based on our
      analysis, areB is predicted to encode at least three distinct protein products.
      These arise from the use of two promoters, differential splicing and translation
      initiating at AUG and non-AUG start codons. All the putative products include a
      GATA domain and a putative Leu zipper. These regions show strong sequence
      similarity to regulatory proteins from Saccharomyces cerevisiae (Dal80p and
      Gzf3p), Penicillium chrysogenum (NREB) and Neurospora crassa (ASD4). We have
      characterized three classes of mutation in areB; the first are loss-of-function
      mutations that terminate the polypeptides within or before the GATA domain. The
      second class truncates the GATA factor either within or upstream of the putative
      Leu zipper but retains the GATA domain. The third class fuses novel gene
      sequences to areB with the potential to produce putative chimeric polypeptides.
      These novel gene fusions transform the putative negative-acting transcription
      factor into an activator that can partially replace areA.

PMID- 11309120
TI  - DNA replication-coupled inactivation of DnaA protein in vitro: a role for DnaA
      arginine-334 of the AAA+ Box VIII motif in ATP hydrolysis.
AB  - The DnaA protein, which initiates chromosomal replication in Escherichia coli, is
      negatively regulated by both the sliding clamp of DNA polymerase III holoenzyme
      and the IdaB protein. We have found that, when the amount of minichromosome is
      limited in an in vitro replication system, minichromosomal replication-stimulated
      hydrolysis of DnaA-bound ATP yields the ADP-bound inactive form. The number of
      sliding clamps formed during replication was at least five per minichromosome,
      which is 2.7-fold higher than the number formed during incubation without
      replication. These results support the notion that coupling of DnaA-ATP
      hydrolysis to DNA replication is the outcome of enhanced clamp formation. We have
      also found that the amino acid substitution R334H in DnaA severely inhibits the
      hydrolysis of bound ATP in vitro. Whereas ATP bound to wild-type DnaA is
      hydrolysed in a DNA-dependent intrinsic manner or in a sliding clamp-dependent
      manner, ATP bound to DnaA R334H protein was resistant to hydrolysis under the
      same conditions. This arginine residue may be located in the vicinity where ATP
      binds, and therefore may play an essential role in ATP hydrolysis. This residue
      is highly conserved among DnaA homologues and also in the Box VIII motif of the
      AAA+ protein family.

PMID- 11309121
TI  - Non-heritable change of a spirochaete's phenotype by decoration of the cell
      surface with exogenous lipoproteins.
AB  - Genetic transformation of Borrelia spp. is limited in development and has found
      application in only one species. For a non-genetic approach for manipulating the
      phenotype of these spirochaetes, we determined whether exogenous recombinant
      lipoproteins would incorporate in the cell's outer membrane. Using unlabelled or
      125I-labelled Osp proteins, Osp-specific monoclonal antibodies, proteinase K and
      formaldehyde as reagents, we found that decoration of spirochaetes had the
      following characteristics. (i) Purified recombinant OspA or OspD lipoproteins
      associated with Borrelia burgdorferi and B. hermsii cells that lacked abundant
      lipoproteins of their own. (ii) This decoration of the cells with exogenous OspA
      did not affect cell's viability. (iii) The decoration was concentration and
      temperature dependent and stable for at least 24 h. (iv) Like native OspA, the
      recombinant OspA decorating the cells was accessible to antibodies and proteases
      and could be cross-linked to the integral outer membrane protein, P66. (v)
      Decoration of viable B. burgdorferi and B. hermsii with OspA rendered the cells
      susceptible to killing by OspA-specific antiserum. Such non-genetic alteration of
      the surface of a bacterium may be used to study functions and properties of
      lipoproteins in situ.

PMID- 11309122
TI  - Genetic dissection of the roles of chaperones and proteases in protein folding
      and degradation in the Escherichia coli cytosol.
AB  - We investigated the roles of chaperones and proteases in quality control of
      proteins in the Escherichia coli cytosol. In DeltarpoH mutants, which lack the
      heat shock transcription factor and therefore have low levels of all major
      cytosolic proteases and chaperones except GroEL and trigger factor, 5-10% and 20
      30% of total protein aggregated at 30 degrees C and 42 degrees C respectively.
      The aggregates contained 350-400 protein species, of which 93 were identified by
      mass spectrometry. The aggregated protein species were similar at both
      temperatures, indicating that thermolabile proteins require folding assistance by
      chaperones already at 30 degrees C, and showed strong overlap with previously
      identified DnaK substrates. Overproduction of the DnaK system, or low-level
      production of the DnaK system and ClpB, prevented aggregation and provided
      thermotolerance to DeltarpoH mutants, indicating key roles for these chaperones
      in protein quality control and stress survival. In rpoH+ cells, DnaK depletion
      did not lead to protein aggregation at 30 degrees C, which is probably the result
      of high levels of proteases and thus suggests that DnaK is not a prerequisite for
      proteolysis of misfolded proteins. Lon was the most efficient protease in
      degrading misfolded proteins in DnaK-depleted cells. At 42 degrees C, ClpXP and
      Lon became essential for viability of cells with low DnaK levels, indicating
      synergistic action of proteases and the DnaK system, which is essential for cell
      growth at 42 degrees C.

PMID- 11309123
TI  - TrlR, a defective TraR-like protein of Agrobacterium tumefaciens, blocks TraR
      function in vitro by forming inactive TrlR:TraR dimers.
AB  - Octopine-type Ti plasmids of Agrobacterium tumefaciens require the quorum-sensing
      proteins TraR and TraI and the diffusible pheromone 3-oxooctanoyl homoserine
      lactone (AAI) to regulate genes required for conjugal transfer. TraR activity is
      inhibited by a protein called TrlR, which closely resembles amino acids 1-181 of
      TraR but is truncated as a result of a shift in the reading frame at codon 182.
      This frameshift does not affect synthesis of the amino-terminal domain, which is
      thought to bind autoinducer and mediate protein dimerization, but abolishes
      translation of the carboxyl-terminal, DNA-binding domain. In this study, we show
      that TrlR, like TraR, requires AAI for solubility when overexpressed in
      Escherichia coli. TrlR bound one molecule of AAI per protein monomer, supporting
      the prediction that the amino-terminal domain of TraR contains the AAI binding
      site. Purified TrlR blocked TraR for both specific DNA binding and transcription
      of a tra promoter, supporting previous studies performed with whole cells. When
      TrlR and a TraR fusion protein were co-expressed in E. coli, these proteins
      readily formed heterodimeric complexes that were inactive in DNA-binding
      activity. These data support the hypotheses that (i) the amino-terminal half of
      TraR binds AAI and mediates protein dimerization; (ii) both DNA-binding domains
      in a TraR dimer are required for stable DNA binding; and (iii) TrlR blocks TraR
      by direct protein-protein interactions.

PMID- 11309124
TI  - Overlapping and distinct roles of the duplicated yeast transcription factors
      Ace2p and Swi5p.
AB  - The yeast transcription factors Ace2p and Swi5p regulate the expression of
      several target genes involved in mating type switching, exit from mitosis and
      cell wall function. We describe the analysis of 12 novel targets, some regulated
      by Ace2p or Swi5p alone and some by both. We show that Ace2p is the major
      regulator of four genes (CTS1, YHR143W, SCW11 and YER124C). Expression of all
      four is inhibited by Swi5p. Like Cts1p and Scw11p, the two new Ace2p targets are
      associated with cell wall metabolism. Yhr143p is localized to the cell wall, and
      deletion affects cell separation and enhances pseudohyphal growth. Deleting
      YER124C also affects cell separation and sensitivity to drugs targeted against
      the cell wall. Expression of PIR1, YPL158C and YNL046W is dependent on Swi5p
      alone. In contrast, expression of YBR158W, YNL078W and YOR264W is minimized when
      both ace2 and swi5 are disrupted. We propose that, although Ace2p and Swi5p co
      operate to induce the expression of a subset of genes, some functional divergence
      has occurred. This results in a delay in the expression of those genes
      predominantly regulated by Ace2p, compared with those predominantly regulated by
      Swi5p.

PMID- 11309125
TI  - Biological cost and compensatory evolution in fusidic acid-resistant
      Staphylococcus aureus.
AB  - Fusidic acid resistance resulting from mutations in elongation factor G (EF-G) of
      Staphylococcus aureus is associated with fitness costs during growth in vivo and
      in vitro. In both environments, these costs can be partly or fully compensated by
      the acquisition of secondary intragenic mutations. Among clinical isolates of S.
      aureus, fusidic acid-resistant strains have been identified that carry multiple
      mutations in EF-G at positions similar to those shown experimentally to cause
      resistance and fitness compensation. This observation suggests that fitness
      compensatory mutations may be an important aspect of the evolution of antibiotic
      resistance in the clinical environment, and may contribute to a stabilization of
      the resistant bacteria present in a bacterial population.

PMID- 11309126
TI  - A novel feature of the multistep phosphorelay in Escherichia coli: a revised
      model of the RcsC --> YojN --> RcsB signalling pathway implicated in capsular
      synthesis and swarming behaviour.
AB  - In this study, we re-investigated the previously characterized RcsC (sensor His
      kinase) --> RcsB (response regulator) phosphorelay system that is involved in the
      regulation of capsular polysaccharide synthesis in Escherichia coli. The
      previously proposed model hypothesized the occurrence of a direct phosphotransfer
      from RcsC to RcsB in response to an unknown external stimulus. As judged from the
      current general view as to the His --> Asp phosphorelay, this RcsC --> RcsB
      framework is somewhat puzzling, because RcsC appears to contain both a His-kinase
      domain and a receiver domain, but not a histidine (His)-containing
      phosphotransmitter domain (e.g. HPt domain). We thus suspected that an as yet
      unknown mechanism might be underlying in this particular His --> Asp phosphorelay
      system. Here, we provide several lines of in vivo and in vitro evidence that a
      novel and unique His-containing phosphotransmitter (named YojN) is essential for
      this signalling system. A revised model is proposed in which the multistep RcsC -
      > YojN --> RcsB phosphorelay is implicated. It was also demonstrated that this
      complex signalling system is somehow involved in the modulation of a
      characteristic behaviour of E. coli cells during colony formation on the surface
      of agar plates, namely swarming.

PMID- 11309127
TI  - MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium
      smegmatis.
AB  - MspA is an extremely stable, oligomeric porin from Mycobacterium smegmatis that
      forms water-filled channels in vitro. Immunogold electron microscopy and an
      enzyme-linked immunosorbent assay demonstrated that MspA is localized in the cell
      wall. An mspA deletion mutant did not synthesize detectable amounts of mspA mRNA,
      as revealed by amplification using mspA-specific primers and reverse-transcribed
      RNA. Detergent extracts of the DeltamspA mutant exhibited a significantly lower
      porin activity in lipid bilayer experiments and contained about fourfold less
      porin than extracts of wild-type M. smegmatis. The chromosome of M. smegmatis
      encodes three proteins very similar to MspA. Sequence analysis of the purified
      porin revealed that mspB or mspC or both genes are expressed in the DeltamspA
      mutant. The properties of this porin, such as single channel conductance, extreme
      stability against denaturation, molecular mass and composition of 20 kDa
      subunits, are identical to those of MspA. Deletion of mspA reduced the cell wall
      permeability towards cephaloridine and glucose nine- and fourfold respectively.
      These results show that MspA is the main general diffusion pathway for
      hydrophilic molecules in M. smegmatis and was only partially replaced by fewer
      porins in the cell wall of the DeltamspA mutant [corrected] This is the first
      experimental evidence that porins are the major determinants of the exceptionally
      low permeability of mycobacteria to hydrophilic molecules.

PMID- 11309128
TI  - A glutamate decarboxylase system protects Listeria monocytogenes in gastric
      fluid.
AB  - We observed that glutamate greatly enhances the survival of Listeria
      monocytogenes in gastric fluid, a phenomenon that is directly linked to glutamate
      decarboxylase activity (GAD). Glutamate-mediated acid tolerance has been
      associated in other intestinal genera with the GAD system, in which glutamate is
      internalized and converted to gamma-aminobutyrate (consuming an intracellular
      proton) that is subsequently exchanged for another extracellular glutamate via a
      membrane-located antiporter. Molecular analysis of L. monocytogenes LO28 revealed
      the presence of two glutamate decarboxylase homologues, designated gadA and gadB,
      that are differentially expressed. The gadB gene is co-transcribed in tandem with
      an upstream gene, gadC, which encodes a potential glutamate/gamma-aminobutyrate
      antiporter. Expression of this transcript is upregulated in response to mild acid
      stress (pH 5.5). In contrast, expression of the monocistronic gadA message was
      weaker and was not induced by mild acid treatment. Non-polar deletion mutations
      resulted in a dramatic decrease in the level of GAD activity and a concomitant
      decrease in acid resistance in the order LO28 > DeltagadA > DeltagadB = DeltagadC
      > DeltagadAB for both stationary and logarithmic phase cultures. The exquisite
      sensitivity of the DeltagadAB mutant to ex vivo porcine and synthetic human
      gastric fluid demonstrates a clear role for the GAD system in facilitating
      survival of the organism in the stomach after ingestion and in other low-pH
      environments. Furthermore, variations in levels of GAD activity between different
      strains of L. monocytogenes correlate significantly with levels of tolerance to
      gastric fluid. Sensitive strains, which include the sequenced L. monocytogenes
      EGD, exhibit reduced levels of GAD activity. It is clear from this study that
      expression of GAD by L. monocytogenes strains is an absolute requirement for
      survival in the stomach environment.

PMID- 11309129
TI  - Regulation of translation elongation in cyanobacteria: membrane targeting of the
      ribosome nascent-chain complexes controls the synthesis of D1 protein.
AB  - The photosystem II reaction centre protein D1 is encoded by the psbA gene. The D1
      protein is stable in darkness but undergoes rapid turnover in the light. Here, we
      show that, in cyanobacterium Synechocystis sp. PCC6803, the synthesis of the D1
      protein is regulated at the level of translation elongation in addition to the
      previously known transcriptional regulation. When Synechocystis sp. PCC6803 cells
      were transferred from light to darkness, the psbA mRNA remained abundant for
      hours. Cytosolic ribosomes were attached to psbA transcripts in the dark, and
      translation continued up to a distinct pausing site. However, ribosome nascent D1
      chain complexes were not targeted to the thylakoid membrane, and no full-length
      D1 protein was produced in darkness. The arrest in translation elongation was
      released in the light, concomitantly with targeting of ribosome D1 nascent-chain
      complexes to the thylakoid membrane, allowing the synthesis of the full-length D1
      protein. Downregulation of membrane targeting of ribosome complexes was also
      observed in the light if damage to the D1 protein was slow. This novel type of
      regulation of prokaryotic translation functions to balance the synthesis and
      degradation of the rapidly turning over photosystem II D1 protein in
      Synechocystis sp. PCC6803.

PMID- 11309130
TI  - Physiological consequences of blocked Caulobacter crescentus dnaA expression, an
      essential DNA replication gene.
AB  - Caulobacter crescentus chromosome replication is precisely coupled to a
      developmental cell cycle. Like most eubacteria, C. crescentus has a DnaA
      homologue that is presumed to initiate chromosome replication. However, the C.
      crescentus replication origin (Cori) lacks perfect consensus Escherichia coli
      DnaA boxes. Instead, the Cori strong transcription promoter (Ps) may regulate
      chromosome replication through the CtrA cell cycle response regulator. We
      therefore created a conditional dnaA C. crescentus strain. Blocking dnaA
      expression immediately decreased DNA synthesis, which stopped after approximately
      one doubling period. Fluorescent flow cytometry confirmed that DNA synthesis is
      blocked at the initiation stage. Cell division also stopped, but not swarmer to
      stalked cell differentiation. All cells became stalked cells that grew as long
      filaments. Therefore, general transcription and protein synthesis continued,
      whereas DNA synthesis stopped. However, transcription was selectively blocked
      from the flagellar fliQ and fliL and methyltransferase ccrM promoters, which
      require CtrA and are blocked by different DNA synthesis inhibitors.
      Interestingly, transcription from Cori Ps continued unaltered. Therefore, Ps
      transcription is not sufficient for chromosome replication. Approximately 6-8 h
      after blocked dnaA expression, cells lost viability exponentially.
      Coincidentally, beta-galactosidase was induced from one transcription reporter,
      suggesting an altered physiology. We conclude that C. crescentus DnaA is
      essential for chromosome replication initiation, and perhaps also has a wider
      role in cell homeostasis.

PMID- 11309131
TI  - The sequence requirements for a functional Escherichia coli replication origin
      are different for the chromosome and a minichromosome.
AB  - We have developed a simple three-step method for transferring oriC mutations from
      plasmids to the Escherichia coli chromosome. Ten oriC mutations were used to
      replace the wild-type chromosomal origin of a recBCsbcB host by recombination.
      The mutations were subsequently transferred to a wild-type host by transduction.
      oriC mutants with a mutated DnaA box R1 were not obtained, suggesting that R1 is
      essential for chromosomal origin function. The other mutant strains showed the
      same growth rates, DNA contents and cell mass as wild-type cells. Mutations in
      the left half of oriC, in DnaA boxes M, R2 or R3 or in the Fis or IHF binding
      sites caused moderate asynchrony of the initiation of chromosome replication, as
      measured by flow cytometry. In mutants with a scrambled DnaA box R4 or with a
      modified distance between DnaA boxes R3 and R4, initiations were severely
      asynchronous. Except for oriC14 and oriC21, mutated oriCs could not, or could
      only poorly, support minichromosome replication, whereas most of them supported
      chromosome replication, showing that the classical definition of a minimal oriC
      is not valid for chromosome replication. We present evidence that the
      functionality of certain mutated oriCs is far better on the chromosome than on a
      minichromosome.

PMID- 11309132
TI  - Type 2-biased expression of cytokine genes in lung granulomatous lesions induced
      by Nippostrongylus brasiliensis infection.
AB  - Infections with helminthic parasites occasionally induce pulmonary diseases with
      possible involvement of immunological mechanisms. In rats infected with the
      nematode Nippostrongylus brasiliensis, pulmonary granulomatous lesions develop
      and persist after the larvae have migrated through the lungs. To determine the
      pathogenesis of this lesion, we examined cytokine gene expression in the lungs
      using RT-PCR and in situ hybridization. Two weeks after infection, when fully
      developed lesions appeared, levels of IL-3 and of type2 cytokines IL-4, IL-5, IL
      6 and IL-13 gene expression were markedly enhanced in whole lung homogenates.
      Those of IL-2 and IFN-gamma were also slightly increased 2 weeks postinfection.
      IL-12 mRNA level did not change after 2 weeks but was slightly increased after 4
      weeks. Levels of IL-10 and proinflammatory cytokine TNF gene expression did not
      show significant changes, although a slight increase was observed in IL-1beta
      message after 2 weeks. In situ hybridization studies showed that lung
      granulomatous lesions were composed mainly of lymphoid cells expressing IL-3, IL
      4 and IL-13 mRNA, but not IFN-gamma mRNA. IL-5 mRNA-expressing cells were fewer
      in number than these cells. RMCP II immunohistochemistry revealed that mast cells
      increased in number in the lung granulomas. From these results, it was concluded
      that the nematode infection-associated lung granuloma was a type 2 lesion.

PMID- 11309133
TI  - Studies on the immunoglobulin E responses to Teladorsagia circumcincta in sheep:
      purification of a major high molecular weight allergen.
AB  - Studies on the immunoglobulin (Ig)E immune responses to the gastric nematode,
      Teladorsagia circumcincta, have demonstrated a major high molecular weight
      allergen (HMWTc). Cross reactive allergens of similar MW were demonstrated for
      Trichostrongylus colubriformis and Cooperia curticei, but not for Haemonchus
      contortus. Purification of HMWTc was achieved by gel-filtration chromatography,
      and nonreducing SDS-PAGE and Western blot analysis revealed two closely
      associated bands with a molecular weight of approximately 140-150 kDa. Reduction
      showed four IgE reactive bands of 120, 50, 45 and 30 kDa, and deglycosylation
      abrogated the immunoreactivity of the 120 and 30 kDa bands. Ultrastructural
      immunolocalization by electron microscopy revealed that the IgE reactivity was
      confined to the cuticular surface of the infective (L3) larvae. ELISA studies to
      determine the IgE anti-HMWTc responses in lambs during their first grazing
      season, demonstrated significantly higher IgE antibody in lambs with low
      accumulative faecal egg count (FEC) compared to animals with high accumulative
      FEC. These studies provide evidence for a protective function of IgE antibody in
      Teladorsagia infections in lambs.

PMID- 11309134
TI  - Vaccination with neutrophil inhibitory factor reduces the fecundity of the
      hookworm Ancylostoma ceylanicum.
AB  - Neutrophil inhibitory factor (NIF), a protein isolated from hookworms of the
      genus Ancylostoma, inhibits CD11b/18-dependent leucocyte function, binding to the
      I domain of CD11b. Historically, NIF was serendipitously isolated from whole worm
      extracts during a search for novel antihaemostatic agents, and little is known of
      its source or biological significance to the parasite. NIF has also been
      identified as a possible hookworm vaccine candidate. Ancylostoma ceylanicum
      recombinant NIF, expressed in its active form in Pichia pastoris, was purified
      and its functional activity confirmed using neutrophil adhesion assays and
      confirmatory immunoassay. Recombinant NIF was subsequently used in vaccination
      trials in the A. ceylanicum-hamster model system for human hookworm infection.
      Vaccinated and challenged animals were not protected in terms of worm burden or
      haematocrit values, despite the presence of high levels of specific antibody
      against NIF. However, adult worms resident in vaccinated animals showed a
      significant reduction in fecundity (85.8% by day 21 postinfection), indicating a
      degree of protection against subsequent transmission by vaccination. These data
      indicate that targeted vaccination with recombinant subunit material, derived
      from a known and effective immune suppressant secreted by the parasite, may offer
      partial protection against the transmission of hookworm infection. Furthermore,
      we can also report that a biological activity characteristic of NIF is detectable
      in the secretions of A. ceylanicum using two complementary bioassays. Complete
      neutralization of this secreted activity by vaccination in combination with other
      vaccine candidates may result in improved protection against A. ceylanicum
      infection.

PMID- 11309135
TI  - Protective immunity to Schistosoma japonicum infection depends on the balance of
      T helper cytokine responses in mice vaccinated with gamma-irradiated cercariae.
AB  - Although the strain difference in protection of mice to Schistosoma mansoni
      infection has been described, limited information is available in the case of
      Schistosoma japonicum. In the present study, we compared the protective immunity
      to S. japonicum infection and cytokine production in various strains of mice
      vaccinated with gamma-irradiated cercariae. A significant reduction in worm
      recovery was observed in male and female mice of DBA/2 at a 6-week interval
      between vaccination and a challenge infection, whereas vaccinated mice of
      C57BL/6, C57BL/10, (C57BL/6 x DBA/2) F1 (B6D2F1) and (C57BL/10 x DBA/2) F1
      (B10D2F1) showed no detectable level of protection. No sex-linked difference in
      development of resistance was observed in any of the strains so far examined.
      Vaccination with gamma-irradiated cercariae twice with a 3-week interval also
      induced significant protection against a challenge infection in DBA/2 but not in
      BALB/c or C57BL/6 strains. Further studies demonstrated that spleen cells of
      vaccinated C57BL/6 mice produced lower levels of IFN-gamma compared to the cells
      of vaccinated BALB/c and DBA/2. On the other hand, production of IL-10 by spleen
      cells was relatively higher in BALB/c mice than in the other two strains.
      Macrophages that had been stimulated with spleen cell culture supernatants
      derived from vaccinated DBA/2 damaged schistosomula more effectively than cells
      stimulated with supernatants derived from the other strains. These results
      suggest that different levels of protection observed among strains of mice depend
      on the balance of cytokine responses which consequently activate or suppress
      macrophage-mediated damage to schistosomula.

PMID- 11309136
TI  - Leishmania immune adherence reaction in vertebrates.
AB  - In normal human blood, C3-opsonized Leishmania promastigotes immune adhere to
      erythrocytes, a mechanism believed to enhance their clearance from blood and
      phagocytosis. Given the potential importance of this reaction in host defence
      against infection, the promastigote-erythrocyte interaction was studied in blood
      of individuals from one avian and 12 mammalian genera; [111In]-labelled
      promastigotes were found to bind only to primate erythrocytes. Nevertheless,
      previous experiments coincubating platelets isolated from nonprimate mammals with
      C3-opsonized promastigotes led to promastigote-platelet adherence. To ascertain
      whether this is a natural mechanism in nonprimate Leishmania infection, normal
      blood from members of Leishmania animal models of interest, dog, guinea-pig,
      hamster, mouse and rabbit, was infected ex vivo with promastigotes. Within 1 min
      of blood contact, the promastigote surface was loaded with platelets, rapidly
      evolving into large aggregates. These results confirm the physiological nature of
      the reaction and demonstrate that promastigote-erythrocyte and promastigote
      platelet binding are the first parasite-host cell encounters after Leishmania
      invasion of primates and nonprimate mammals, respectively. Leishmania immune
      adherence shares the characteristics of the nonanticipatory immune systems, and
      we consider it should be viewed as an innate vertebrate host effector mechanism.

PMID- 11309137
TI  - CD1d-restricted NK T cells are dispensable for specific antibody responses and
      protective immunity against liver stage malaria infection in mice.
AB  - Immunization with a single dose of irradiated sporozoites is sufficient to induce
      protection against malaria in wild-type mice. Although this protection is
      classically attributed to conventional CD4+ and CD8+ T cells, several recent
      reports have suggested an important role for CD1-restricted NK T cells in
      immunity to malaria. In this study, we directly compared the ability of C57BL/6
      wild-type and CD1-deficient mice to mount a protective immune response against
      Plasmodium berghei sporozoites. Our data indicate that CD1-restricted NK T cells
      are not required for protection in this model system. Moreover, specific IgG
      antibody responses to the P. berghei circumsporozoite repeat sequence were also
      unaffected by CD1 deficiency. Collectively, our data demonstrate that CD1
      restricted NK T cells are dispensable for protective immunity to liver stage P.
      berghei infection.

PMID- 11309138
TI  - Chain-length specificities of maize starch synthase I enzyme: studies of glucan
      affinity and catalytic properties.
AB  - It is widely known that some of the starch synthases and starch-branching enzymes
      are trapped inside the starch granule matrix during the course of starch
      deposition in amyloplasts. The objective of this study was to use maize SSI to
      further our understanding of the protein domains involved in starch granule
      entrapment and identify the chain-length specificities of the enzyme. Using
      affinity gel electrophoresis, we measured the dissociation constants of maize SSI
      and its truncated forms using various glucans. The enzyme has a high degree of
      specificity in terms of its substrate-enzyme dissociation constant, but has a
      greatly elevated affinity for increasing chain lengths of alpha-1, 4 glucans.
      Deletion of the N-terminal arm of SSI did not affect the Kd value. Further small
      deletions of either N- or C-terminal domains resulted in a complete loss of any
      measurable affinity for its substrate, suggesting that the starch-affinity domain
      of SSI is not discrete from the catalytic domain. Greater affinity was displayed
      for the amylopectin fraction of starch as compared to amylose, whereas glycogen
      revealed the lowest affinity. However, when the outer chain lengths (OCL) of
      glycogen were extended using the phosphorylase enzyme, we found an increase in
      affinity for SSI between an average OCL of 7 and 14, and then an apparently
      exponential increase to an average OCL of 21. On the other hand, the catalytic
      ability of SSI was reduced several-fold using these glucans with extended chain
      lengths as substrates, and most of the label from [14C]ADPG was incorporated into
      shorter chains of dp < 10. We conclude that the rate of catalysis of SSI enzyme
      decreases with the OCL of its glucan substrate, and it has a very high affinity
      for the longer glucan chains of dp approximately 20, rendering the enzyme
      catalytically incapable at longer chain lengths. Based on the observations in
      this study, we propose that during amylopectin synthesis shorter A and B1 chains
      are extended by SSI up to a critical chain length that soon becomes unsuitable
      for catalysis by SSI and hence cannot be elongated further by this enzyme.
      Instead, SSI is likely to become entrapped as a relatively inactive protein
      within the starch granule. Further glucan extension for continuation of
      amylopectin synthesis must require a handover to other SS enzymes which can
      extend the glucan chains further or for branching by branching enzymes. If this
      is correct, this proposal provides a biochemical basis to explain how the
      specificities of various SS enzymes determine and set the limitations on the
      length of A, B, C chains in the starch granule.

PMID- 11309139
TI  - Peroxisomal alanine : glyoxylate aminotransferase (AGT1) is a photorespiratory
      enzyme with multiple substrates in Arabidopsis thaliana.
AB  - At least two glyoxylate aminotransferases are hypothesized to participate in the
      steps of photorespiration located in peroxisomes. Until recently, however, genes
      encoding these enzymes had not been identified. We describe the isolation and
      characterization of an alanine : glyoxylate aminotransferase (AGT1, formerly AGT)
      cDNA from Arabidopsis thaliana. Southern blot analysis confirmed that Arabidopsis
      AGT1 is encoded by a single gene. Homologs of this class IV aminotransferase are
      also known in other plants, animals, and methylotrophic bacteria, suggesting an
      ancient evolutionary origin of this enzyme. AGT1 transcripts were present in all
      tissues of Arabidopsis, but were most abundant in green, leafy tissues. Purified,
      recombinant Arabidopsis AGT1 expressed in Escherichia coli catalyzed three
      transamination reactions using the following amino donor : acceptor combinations:
      alanine : glyoxylate, serine : glyoxylate, and serine : pyruvate. AGT1 had the
      highest specific activity with the serine : glyoxylate transamination, and
      apparent Km measurements indicate that this is the preferred in vivo reaction. In
      vitro import experiments and subcellular fractionations localized AGT1 to
      peroxisomes. Sequence analysis of the photorespiratory sat mutants revealed a
      single nucleotide substitution in the AGT1 gene from these plants. This
      transition mutation is predicted to result in a proline-to-leucine substitution
      at residue 251 of AGT1. When this mutation was engineered into the recombinant
      AGT1 protein, enzymatic activity using all three donor : acceptor pairs was
      abolished. We conclude that Arabidopsis AGT1 is a peroxisomal photorespiratory
      enzyme that catalyzes transamination reactions with multiple substrates.

PMID- 11309140
TI  - The gene fimbriata interacts non-cell autonomously with floral regulatory genes.
AB  - In Antirrhinum majus, one proposed role of the gene fimbriata (fim) is as a
      mediator between the floral meristem identify gene floricaula (flo) and floral
      organ identity genes such as deficiens (def) and plena (ple). The mechanism of
      fim activity is probably unique as, while the other genes in the hierarchy are
      thought to be transcription factors, fim is thought to target proteins to a
      ubiquitin-mediated destruction pathway. Both flo and def have been shown to act
      non-cell autonomously. We tested the hypotheses that (i) fim acts in a non-cell
      autonomous manner; and (ii) non-cell autonomy of flo might be through activation
      and subsequent non-cell autonomous activity of fim. Plants bearing an unstable
      fim allele were monitored for revertant shoots. Analysis of fim RNA expression in
      plants derived from revertant shoots, and segregation of revertant phenotype in
      progeny from revertant plants, indicated that all were periclinal chimeras with
      wild-type fim expression only in subepidermal layers. Despite the absence of fim
      in the epidermal layer, expression of downstream genes was normal, suggesting non
      cell autonomous activity of fim. Subsequently, we tested the hypothesis that fim
      is the mediator of flo non-cell autonomy by examining fim expression in flo
      periclinal chimeras. In these chimeras, fim is activated in cells where flo is
      not expressed, indicating that fim cannot be the sole mediator of flo non-cell
      autonomy.

PMID- 11309141
TI  - Gibberellin response mutants identified by luciferase imaging.
AB  - The gibberellin (GA) 20-oxidase encoded by Arabidopsis GA5 catalyzes the
      synthesis of active GAs. GA5 is a regulatory step in GA biosynthesis as GA5 mRNA
      levels are negatively regulated by its bioactive GA products. A fusion between
      the GA5 promoter and the firefly luciferase reporter (GA5-LUC) was shown to be
      similarly regulated, indicating GA feedback of GA5 occurs at the transcriptional
      level. The fidelity of the GA5-LUC reporter permitted a fusion genetic screen to
      identify mutants altered in transgene expression. This bioimaging screen
      identified two types of recessive mutants with increased LUC activity and
      apparent GA-related growth phenotypes, a dwarf (lue1) and two late flowering
      mutants (fpa1-3 and fpa1-4). Mutant progeny exhibited altered levels of LUC and
      of endogenous GA5 and other GA-regulated mRNAs. SSLP-based mapping localized lue1
      to chromosome I near the ga2 locus, although complementation analyzes showed that
      lue1 is not allelic to ga2. Mapping and complementation analyzes showed that the
      late flowering mutants are allelic to fpa1. This provides genetic evidence for
      crosstalk between the autonomous and gibberellin-dependent flowering pathways.

PMID- 11309142
TI  - Evidence for the plant-specific intercellular transport of the Arabidopsis copper
      chaperone CCH.
AB  - Arabidopsis copper chaperone (CCH) belongs to a family of eukaryotic proteins
      that participates in intracellular copper homeostasis by delivering this metal to
      the secretory pathway. In this work we show that the CCH protein is mainly
      located along the vascular bundles of senescing leaves and petioles, as shown by
      tissue prints and immunohistochemical detection. CCH protein also accumulates in
      stem sieve elements and is collected in phloem exudates. Accordingly, Arabidopsis
      CCH is the only member of the metallochaperone family described to function
      intercellularly to date. Moreover, the CCH protein remains stable when plants are
      subjected to excess copper that causes a rapid and specific decrease in its mRNA.
      These facts point to a role for CCH in copper mobilization from decaying organs
      towards reproductive structures, as a result of metalloprotein breakdown.

PMID- 11309143
TI  - Effects of urate, a natural inhibitor of peroxynitrite-mediated toxicity, in the
      response of Arabidopsis thaliana to the bacterial pathogen Pseudomonas syringae.
AB  - Urate, a natural peroxynitrite scavenger, has been used to investigate the
      possible role of peroxynitrite during plant-pathogen interactions. Urate greatly
      reduced lesion formation in Arabidopsis leaves treated with an abiotic
      peroxynitrite-generating system or with a peroxynitrite solution, indicating that
      it can act as an effective scavenger in planta. In the interaction with the
      avirulent Pseudomonas syringae pv. phaseolicola (avrRPM1+), cell death in the
      inoculated area was strongly reduced by urate, without compromising disease
      resistance. In contrast, urate promoted discrete cell death in response to an
      isogenic Pseudomonas syringae (avrRPM1-), which did not trigger an HR when
      inoculated alone, and it induced resistance and arrest of pathogen growth.
      Scavenging of peroxynitrite did not modify the response of Arabidopsis to an
      avirulent strain of Xanthomonas campestris pv campestris, that showed a high
      resistance to NO and peroxynitrite. Our data indicate that peroxynitrite plays a
      significant role in the responses of plants to Pseudomonas syringae.

PMID- 11309144
TI  - Hyperosmotic stress rapidly generates lyso-phosphatidic acid in Chlamydomonas.
AB  - Plant cells are continuously exposed to environmental stresses such as hyper
      osmolarity, and have to respond in order to survive. When 32P-labelled
      Chlamydomonas moewusii cells were challenged with NaCl, the formation of a new
      radiolabelled phospholipid was stimulated, which was barely detectable before
      stimulation. The phospholipid was identified as lyso-phosphatidic acid (LPA), and
      was the only lyso-phospholipid to be accumulated. The increase in LPA was dose-
      and time-dependent. When other osmotically active compounds were used, the
      formation of LPA was also induced with similar kinetics, although salts were
      better inducers than non-salts. At least part of the LPA was generated by
      phospholipase A2 (PLA2) hydrolysing phosphatidic acid (PA). This claim is based
      on PA formation preceding LPA production, and PLA2 inhibitors decreasing the
      accumulation of LPA and promoting the conversion of PA to diacylglycerol
      pyrophosphate. The latter is another metabolic derivative of PA that is
      implicated in cell signalling. The involvement of multiple lipid-signalling
      pathways in hyperosmotic stress responses is discussed.

PMID- 11309145
TI  - Regulation of HEMA1 expression by phytochrome and a plastid signal during de
      etiolation in Arabidopsis thaliana.
AB  - The synthesis of 5-aminolevulinic acid (ALA) is the rate-limiting step for the
      formation of all plant tetrapyrroles, including chlorophyll and heme, and
      regulation of ALA synthesis is therefore critical to plant development. Glutamyl
      tRNA reductase (GluTR) is the first committed enzyme of this pathway and is
      encoded by a small family of nuclear HEMA genes. Here, we have used transgenic
      Arabidopsis (Arabidopsis thaliana L. Col) lines expressing chimeric HEMA1
      promoter:gusA fusion genes, combined with RNA gel blot analyses, to characterise
      the light-mediated regulation of the Arabidopsis HEMA1 gene during de-etiolation.
      HEMA1 was expressed strongly, but not exclusively, in photosynthetic tissues and
      was shown to be light regulated at the transcriptional level by the phytochrome
      family of photoreceptors acting in both the far-red high irradiance and low
      fluence response modes. The HEMA2 gene, which is expressed only in roots of
      seedlings, was not light regulated. Analysis of truncated HEMA1 promoter
      constructs demonstrated that a -199/+252 promoter fragment was sufficient to
      confer full light-responsiveness to gusA expression. This fragment contained GT
      1/I-box and CCA-1 binding sites that are implicated as the light-responsive cis
      elements. Both the full-length and truncated HEMA1 promoters required the
      presence of intact chloroplasts for full expression, consistent with previous
      indications that light and plastid factor signals converge to co-ordinately
      regulate expression of photosynthesis-related nuclear genes. These results
      provide the most comprehensive analysis to date of the light-regulation of a
      tetrapyrrole biosynthetic gene and support a direct link between regulation of
      HEMA1 transcription and chlorophyll accumulation during seedling de-etiolation.

PMID- 11309146
TI  - A recessive mutation in the Arabidopsis SSI2 gene confers SA- and NPR1
      independent expression of PR genes and resistance against bacterial and oomycete
      pathogens.
AB  - The Arabidopsis thaliana NPR1 gene is required for salicylic acid (SA)-induced
      expression of pathogenesis-related (PR) genes and systemic acquired resistance.
      However, loss-of-function mutations in NPR1 do not confer complete loss of PR
      gene expression or disease resistance. Thus these responses also can be activated
      via an NPR1-independent pathway that currently remain to be elucidated. The ssi2
      1 mutant, identified in a genetic screen for suppressors of npr1-5, affects
      signaling through the NPR1-independent defense pathway(s). In comparison with the
      wild-type (SSI2 NPR1) plants and the npr1-5 mutant (SSI2 npr1-5), the ssi2-1 npr1
      5 double mutant and the ssi2-1 NPR1 single mutant constitutively express PR genes
      [PR-1, BGL2 (PR-2) and PR-5]; accumulate elevated levels of SA; spontaneously
      develop lesions; and possess enhanced resistance to a virulent strain of
      Peronospora parasitica. The ssi2-1 mutation also confers enhanced resistance to
      Pseudomonas syringae pv. tomato (Pst); however, this is accomplished primarily
      via an NPR1-dependent pathway. Analysis of ssi2-1 NPR1 nahG and ssi2-1 npr1-5
      nahG plants revealed that elevated SA levels were not essential for the ssi2-1
      conferred phenotypes. However, expression of the nahG transgene did reduce the
      intensity of some ssi2-1-conferred phenotypes, including PR-1 expression, and
      disease resistance. Based on these results, SSI2 or an SSI2-generated signal
      appears to modulate signaling of an SA-dependent, NPR1-independent defense
      pathway, or an SA- and NPR1-independent defense pathway.

PMID- 11309147
TI  - The S-methylmethionine cycle in angiosperms: ubiquity, antiquity and activity.
AB  - Angiosperms synthesize S-methylmethionine (SMM) from methionine (Met) and S
      adenosylmethionine (AdoMet) in a unique reaction catalyzed by Met S
      methyltransferase (MMT). SMM serves as methyl donor for Met synthesis from
      homocysteine, catalyzed by homocysteine S-methyltransferase (HMT). MMT and HMT
      together have been proposed to constitute a futile SMM cycle that stops the free
      Met pool from being depleted by an overshoot in AdoMet synthesis. Arabidopsis and
      maize have one MMT gene, and at least three HMT genes that belong to two
      anciently diverged classes and encode enzymes with distinct properties and
      expression patterns. SMM, and presumably its cycle, must therefore have
      originated before dicot and monocot lineages separated. Arabidopsis leaves, roots
      and developing seeds all express MMT and HMTs, and can metabolize [35S]Met to
      [35S]SMM and vice versa. The SMM cycle therefore operates throughout the plant.
      This appears to be a general feature of angiosperms, as digital gene expression
      profiles show that MMT and HMT are co-expressed in leaves, roots and reproductive
      tissues of maize and other species. An in silico model of the SMM cycle in mature
      Arabidopsis leaves was developed from radiotracer kinetic measurements and pool
      size data. This model indicates that the SMM cycle consumes half the AdoMet
      produced, and suggests that the cycle serves to stop accumulation of AdoMet,
      rather than to prevent depletion of free Met. Because plants lack the negative
      feedback loops that regulate AdoMet pool size in other eukaryotes, the SMM cycle
      may be the main mechanism whereby plants achieve short-term control of AdoMet
      level.

PMID- 11309148
TI  - cDNA microarray analysis of small plant tissue samples using a cDNA tag target
      amplification protocol.
AB  - Microarray technology is becoming an important comprehensive tool to study gene
      expression in plants. However, the use of this technology is limited by the large
      amount of sample tissue needed for microarray analysis. Generally, 50-200 microg
      of total RNA and 1-2 microg of mRNA is required for each hybridisation, which is
      equivalent to 50-100 mg of plant tissue. This requirement for large amounts of
      starting material severely constrains the use of microarrays for transcript
      profiling in specific tissues and cell types during plant development. Here we
      report on a robust and reliable target amplification method that enables
      transcript profiling from sub-mg amounts of plant tissue. Using 0.1 microg of
      total RNA we show that twofold expression differences are possible to distinguish
      with 99% confidence. We also demonstrate the application of this method in an
      analysis of secondary phloem development in hybrid aspen using defined tissue
      sections, corresponding to 2-4 cell layers with a fresh weight of approximately
      0.5 mg.

PMID- 11309149
TI  - Helicobacter pylori vaccines: lessons from small animal models.

PMID- 11309150
TI  - Vaccination against Helicobacter pylori in non-human primate models and humans.
AB  - Several vaccination studies have been performed in monkeys and humans testing the
      feasibility of prophylactic and therapeutic immunizations against Helicobacter
      pylori. The monkey studies showed that immune responses were induced by oral
      vaccination with the mucosal adjuvant LT (Escherichia coli heat-labile
      enterotoxin), parenteral administration with a cationic lipid adjuvant, and by
      mucosal priming followed by parenteral boosts. Both prophylactic and therapeutic
      activities were demonstrated in monkeys, providing a strong impetus for human
      vaccine trials. Preliminary studies in humans were undertaken in order to
      identify a tolerable dose of LT adjuvant or to test the effectiveness of mutant
      atoxic LT adjuvants. The results from these preliminary studies suggest that
      native LT causes diarrhoea at doses required for adjuvanticity while a mutant LT
      does not. In one study in which infected human subjects were vaccinated with
      orally administered urease antigen with native LT, there was a modest reduction
      in the level of H. pylori gastric colonization. A second clinical study employing
      H. pylori whole cell antigen and a mutant LT in infected subjects showed immune
      responses and although the subjects remained infected, the study was not designed
      to measure reduction in H. pylori colonization. Recombinant Salmonella expressing
      urease and other H. pylori antigens have been effective in mice (see accompanying
      Frontlines Topic Review by John O. Nedrud [1]), but monkey studies are not
      possible because of host range restriction. Human trials of parenteral
      immunization, mucosal immunization with mutant LT and live Salmonella vectors are
      needed to fully assess the ability of vaccines to prevent or treat H. pylori
      infections.

PMID- 11309151
TI  - Helicobacter pylori vaccine development in the post-genomic era: can in silico
      translate to in vivo.

PMID- 11309152
TI  - Inhibition of dipeptidyl peptidase IV (DP IV, CD26) activity abrogates stress
      induced, cytokine-mediated murine abortions.
AB  - In the CBA x DBA/2 mouse model, stress-triggered abortions are mediated by a Th1
      like cytokine response of decidual lymphocytes. The factors that determine the
      cytokine pattern leading to abortion are currently unknown. Dipeptidyl Peptidase
      IV (DP IV) enhances Th1-cytokine responses and impairs the evolvement of a Th2
      cytokine profile. The T-cell-activation antigen, CD26, possesses DP IV activity.
      The aim of the present study was to investigate the role of DP IV activity and
      CD26-positive decidual lymphocytes in murine stress-triggered abortions by
      inhibition of DP IV activity. DBA/2-mated CBA mice were stressed on day 5.5 of
      pregnancy and received daily injections of an inhibitor of DP IV activity, Ile
      thiazolidide (20 micromol/kg). On day 13 of gestation, the animals were
      sacrificed and the percentage of implants and abortions documented. CD26-positive
      lymphocytes in spleen and uterine decidua and the intracellular cytokines
      interferon (IFN)-gamma and interleukin (IL)-10 were determined by flow cytometry.
      Stressed and nonstressed animals receiving an inactive stereoisomeric form were
      used as controls. In mice receiving the DP IV inhibitor, stress failed to boost
      the abortion rate (37.2% versus 13.6%, P < 0.01). IFN-gamma producing cells were
      increased in stressed animals, but returned to the baseline upon the inhibition
      of DP IV. The number of IL-10 producing cells was reduced in stressed animals,
      independent from DP IV inhibition.

PMID- 11309153
TI  - CD40L-induced IL-12 production is further enhanced by the Th2 cytokines IL-4 and
      IL-13.
AB  - Interaction of the CD40L (CD154) molecule on activated T cells with its receptor,
      CD40, on macrophages and dendritic cells (DC) provides a strong signal for
      interleukin (IL)-12 production. As IL-12 is the most important factor in driving
      Th precursor (Thp) cells into T(h)elper 1 cells, CD40-CD40L interactions strongly
      promote Th1 differentiation. Th2 cytokines (IL-4, IL-13, IL-10) on the other
      hand, are known to inhibit Th1 differentiation, and to promote either directly or
      indirectly, Th2 differentiation. Inhibition of lipopolysaccharide (LPS)-induced
      IL-12 production by IL-4, IL-13 and IL-10 is supposed to be one such mechanism.
      However, we here report that IL-4 and IL-13 enhance p70 IL-12 production and p40
      mRNA transcription by human monocytes when the latter are stimulated trough
      triggering of CD40. This effect on IL-12 induction is most clear in the presence
      of interferon (IFN)-gamma, which upregulates CD40 expression. IL-10 potently
      inhibits IL-12 production. The increased IL-12 production in the presence of IL-4
      and IL-13 is however, not the indirect result of a reduction in IL-10 production,
      but is most likely owing to a direct effect of IL-4 and IL-13. We conclude that
      IL-4 and IL-13 enhance rather than decrease the IL-12 production by human
      monocytes during interaction with T cells. This effect can potentially contribute
      in vivo to switching of an ongoing Th2 response towards a Th1 response and the
      findings also support the dominant effect of CD40/CD40L interaction on Th1
      development, even in the presence of Th2 cytokines.

PMID- 11309154
TI  - A role for complement C5 in organism containment and granulomatous response
      during murine tuberculosis.
AB  - The molecular mechanisms underlying protective granuloma formation and control of
      bacterial growth during infection with Mycobacterium tuberculosis (MTB) are not
      yet completely understood. MTB-infected mice with natural deficiency in
      complement component C5 are unable to develop productive granulomatous responses,
      and are impaired in limiting organism growth within the lung. To address the
      molecular basis for this histologic dysfunction, congenic complement C5
      sufficient (B10.D2-H2d H2-T18c Hcl/nSnJ) and complement C5-deficient strains
      (B10.D2-H2d H2-T18c Hco/oSnJ) congenic mice were infected with Mycobacterium
      tuberculosis, and cytokine and chemokine responses were examined. Twelve and 28
      days after infection, lungs showed elevated messages for multiple inflammatory
      cytokines in both congenic strains. Interleukin (IL)-12(p40) mRNA was also
      induced during infection in C5-deficient mice, although levels were significantly
      decreased compared to C5-sufficient congenics. C5-deficient mice also
      demonstrated reduced KC, MIP-2, IP-10, and MCP-1 mRNA. The defect may directly
      involve C5-mediated effects on macrophage responses; C5-deficient bone marrow
      derived macrophages had significantly reduced secretion of KC, MIP-1 alpha and
      MIP-2 compared to C5-sufficient macrophages following in vitro infection. These
      findings indicate a role for C5 in mediation of chemotactic and activation events
      that are the basis for granulomatous responses during murine tuberculosis.

PMID- 11309155
TI  - Effect of maternal antibodies on influenza virus-specific immune response
      elicited by inactivated virus and naked DNA.
AB  - While vaccines are effective in adults, they are less successful in newborns and
      infants. Neonatal unresponsiveness to vaccines could be owing to immaturity of
      lymphocytes and/or to inhibition by maternal antibodies. Unresponsiveness of
      newborn to vaccines can be overcame by genetic immunization. In the present study
      we investigated the effect of maternal antibodies on the anti-influenza virus
      protective response in progeny born to dams immunized with plasmid containing the
      hemagglutinin gene or UV-inactivated virus. The effect of maternal antibodies was
      studied in plasmid immunized F1 mice born to BALB/c dams, previously immunized
      with virus or plasmid and crossed with C57BL/6 males, as well as in offspring
      born to BALB/c dams immunized with plasmid and then immunized with UV-inactivated
      WSN virus. We have found that the inhibition period of the anti-HA antibody
      response in offspring born to dams immunized with DNA is shorter than that of
      offspring born to dams immunized with virus. Furthermore, there is a persistent
      inhibitory effect on B cells from offspring born to dams immunized with virus or
      injected with antiviral monoclonal antibodies (MoAb), after the decline of
      maternal antibody titers. The analysis of the haemagglutinin-specific clonotype
      reactivity pattern of offspring born to dams immunized with inactivated influenza
      virus or with a plasmid showed that clonotypes producing antibodies specific for
      the immunizing virus strain were predominant in offspring born to dams immunized
      with DNA compared to those born to dams immunized with virus. Maternal antibodies
      do not affect cell-mediated immunity. These findings might be used to design
      efficient vaccination schedules for newborns and infants.

PMID- 11309156
TI  - Presence of IL-4-like molecules in larval excretory-secretory products and crude
      extracts from Anisakis simplex.
AB  - Acute symptoms of anisakidosis are caused by a type I allergic reaction in the
      gastrointestinal wall with elevated specific immunoglobulin (Ig)E. The purpose of
      this study was to investigate the presence of interleukin (IL)-4 in the larval
      antigens of Anisakis simplex. We detected concentrations of IL-4 in pg/ml when
      larval excretory--secretory products and crude extract from A. simplex were
      investigated by ELISA. Specific antibodies were obtained by immunization of
      rabbits with mouse IL-4 and tested in ELISA against A. simplex antigens obtaining
      higher values of optical density, that were confirmed by western blot analysis.
      The absorption of these sera with A. simplex antigen resulted in a 70--80%
      inhibition of antigen binding when retested in ELISA. We demonstrated that A.
      simplex antigens react with antibodies raised against vertebrate IL-4. The
      results obtained by us support the hypothesis that A. simplex shares several
      epitopes with IL-4, important for the Th2 response development in human
      anisakiasis, where the parasite may modulate the Th1--Th2 dichotomy for its own
      benefit by mucosal inflammation control in an attempt to avoid the larval
      expelling.

PMID- 11309157
TI  - Characterization and quantification of mouse mannan-binding lectins (MBL-A and
      MBL-C) and study of acute phase responses.
AB  - Rat monoclonal antibodies (MoAbs) against mouse mannan-binding lectin (MBL)-A and
      MBL-C were generated and assays for MBL-A and MBL-C were constructed. This
      allowed for the quantitative analysis of both proteins for the first time.
      Previously only MBL-A has been quantified using less standardized methods. In a
      mouse serum pool the concentrations were now determined at 7.5 microg MBL-A and
      45 microg MBL-C per ml. On gel permeation chromatography of mouse serum, MBL-A
      eluted corresponding to a M(r) of 850 kDa whereas the majority of MBL-C eluted
      corresponding to a Mr of 950 kDa. On sucrose density gradient centrifugation the
      sedimentation velocities of MBL-A and MBL-C were estimated at 7.3 S and 10.8 S,
      respectively. The MBL-A and MBL-C levels in 10 laboratory mice strains were
      compared and found to vary between 4 microg/ml to 12 microg/ml, and 16 microg/ml
      to 118 microg/ml, respectively. After the induction of acute phase responses by
      intraperitoneal injection of either casein or lipopolysaccharide (LPS), MBL-A was
      found to increase approximately two-fold, with a maximum after 32 h, while MBL-C
      did not increase significantly. In comparison, serum amyloid A component (SAA)
      peaked at 15 h with an approximate 100-fold increase.

PMID- 11309158
TI  - Novel monoclonal antibodies against major antigens of Mycobacterium bovis.
AB  - MPB70 and MPB83 are among the most characteristically exported proteins defining
      a strongly expressed phenotype of Mycobacterium bovis. These proteins are known
      to be homologous to osteoblast-specific factor 2. By in vitro culture of
      mycobacteria they appear to have a limited species distribution and to be
      relatively specific for M. bovis. Virtually identical genes are however, present
      in Mycobacterium tuberculosis. In order to facilitate further research into the
      immunobiology of these proteins and their potential application for differential
      diagnosis of tuberculosis as a result of M. bovis, we describe the reactivities
      of 20 monoclonal antibodies (MoAbs) to these proteins. Immunizing with bovine PPD
      generated 10 MoAbs. These antibodies reacted preferentially with the soluble
      MPB70 antigen using reducing conditions in SDS-PAGE with western blotting. Ten
      MoAbs were generated by immunizing mice with fractions derived from a whole cell
      sonic extract of M. bovis. These antibodies reacted preferentially with the
      surface exposed MPB83 lipoglycoprotein.

PMID- 11309159
TI  - Analysis of Ig kappa light chain gene variable regions expressed in the
      rheumatoid synovial B cells.
AB  - Sequence analysis of antibody variable (V) regions can provide an insight
      regarding whether B cells have gone through an antigen-driven process of affinity
      maturation. In this study, we analyzed 16 V-regions of immunoglobulin (Ig) kappa
      light chain genes obtained from a cDNA library of a rheumatoid arthritis (RA)
      synovial tissue. A salient feature of our results is the high frequency
      utilization of germline V kappa I family genes, especially the O2/O12 gene (38%).
      All kappa V-regions showed extensive somatic hypermutation with 5.4% of an
      average mutation rate. Replacement to silent mutation (R/S) ratio in the
      complementarity determining region (CDR) was > 2.9 in 12 out of 16 clones,
      indicating that the majority of the RA synovial B cells had undergone affinity
      maturation. However, the four other clones showed R/S ratios of < 2.9 in the CDR
      despite a high mutation rate. In contrast to the previous reports, long CDR3 was
      not a characteristic feature of these clones. In summary, these data show the
      high frequency utilization of the germline O2/O12 gene and a high rate of
      mutation with an evidence of antigen selection in most of the Ig kappa genes
      expressed in the RA synovium.

PMID- 11309160
TI  - Cytokine expression in unstimulated PBMC of children with type 1 diabetes and
      subjects positive for diabetes-associated autoantibodies.
AB  - The aim of this study was to evaluate possible changes in the circulating levels
      of interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor
      (TGF)-beta in association with the autoimmune process leading to type 1 diabetes.
      Expression levels of mRNAs specific for each cytokine were determined in
      peripheral blood mononuclear cells (PBMC) by a multiplex reverse transcription
      polymerase chain reaction (RT-PCR) followed by hybridization reactions with
      lanthanide-labelled probes and detection by time-resolved fluorometry. Newly
      diagnosed diabetic children had lower levels of IFN-gamma, IL-4 and TGF-beta 1
      signals compared to their age- and sex-matched controls (P < 0.02, P < 0.005 and
      P < 0.005, respectively) and also the autoantibody-positive subjects had
      significantly lower levels of IL-4 and TGF-beta 1 in comparison with their
      matched controls (P = 0.0013 and P = 0.012). No significant differences were
      observed when comparing matched pairs of diabetic children and autoantibody
      positive subjects. Our results suggest a systemic bias towards reduced production
      of T-helper cell type 2 cytokines (IL-4 and TGF-beta 1) during the autoimmune
      process, but there was also a reduced level of IFN-gamma expression in the
      periphery at the onset of clinical diabetes.

PMID- 11309161
TI  - alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease:
      further evidence of persistent immune activation.
AB  - We have previously shown that titers of soluble platelet selectin (s-P-selectin)
      and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera
      of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed
      the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x
      (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients
      with Chagas' disease at different levels of disease severity. Patients with a
      mild form of Chagas' disease showed a lower number of CD49d(+) cells, in
      comparison with those with severe chronic cardiopathy. Decreased levels of
      CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x)
      expression was found to be decreased in patients with severe Chagas' disease.
      Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were
      significantly increased in the plasma of patients with severe Chagas' disease
      while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P
      Selectin ligands are differentially expressed during the chronic phase of the
      Trypanosoma cruzi infection. These findings also reinforce a role of the P
      selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1,
      in the pathogenesis of Chagas' disease.

PMID- 11309162
TI  - Connectivity patterns in tuberculosis and leprosy patients are indistinguishable
      from that of healthy donors.
AB  - Connectivity, the self-defined interactions between antigen-recognising molecules
      in a network system can in part be assessed by measuring the reactivity of a
      given serum against an ordered set of immunoglobulin (Ig)G F(ab')2 fractions,
      separated by means of isoelectric focusing so that, the serum reactivity against
      the whole set of fractions defines a characteristic pattern of connectivity.
      Deviations from the normal condition (healthy donors) have so far been documented
      for two autoimmune diseases: systemic lupus erythematosus (SLE) and pemphigus
      vulgaris, as well as for human immunodeficiency virus (HIV)-1 infection. We
      tested here if bacterial infections lead to alterations in connectivity. In
      addition, we wanted to test if two antigenically related bacteria would produce
      similar or otherwise distinctive connectivity patterns. Connectivity analysis was
      applied on the sera from tuberculosis and leprosy patients and the sera from
      healthy donors were used as control. No statistically significant differences
      between the three groups studied were found. These results have implications for
      theories that set the origin of autoimmune diseases in microbial infections. To
      the best of our knowledge, this is the first attempt to analyze the connectivity
      status in bacterial infections.

PMID- 11309163
TI  - Knowledge, education, research and the Web.

PMID- 11309165
TI  - Placing value on pictures: what information is there in color flow images and how
      can we use it?

PMID- 11309166
TI  - Natural history of fetal hydronephrosis diagnosed on mid-trimester ultrasound.
AB  - OBJECTIVES: Renal tract dilatation is a common finding in routine prenatal
      ultrasound. However, there is no consensus as to the criteria used for
      differentiating pathological from physiological dilatation. The aim of this study
      was to evaluate the natural history and postnatal outcome of fetal hydronephrosis
      in an unselected obstetric population. DESIGN: This was a prospective study of
      fetal hydronephrosis, detected at 18-23 weeks' gestation, in a routine obstetric
      population. Fetal hydronephrosis was diagnosed as 'mild' if the antero-posterior
      renal pelvic diameter (APRPD) measured >or = 4 mm and as 'moderate/severe' if the
      APRPD measured > or = 7 mm or if there was associated calyceal dilatation. The
      postnatal outcome of fetuses with persistent hydronephrosis (> or = 10 mm in the
      third trimester) was determined from a postal questionnaire. RESULTS: During the
      study period, 11 465 women underwent an anomaly scan at 18-23 weeks of gestation.
      Fetal hydronephrosis was identified in 2.3% (268/11 465) of women. Mild
      hydronephrosis was present in 80.6% (216/268) and moderate/severe hydronephrosis
      in 19.4% (52/268). The hydronephrosis resolved in the antenatal or early neonatal
      period in 88% of fetuses. None of the fetuses with mild hydronephrosis and
      approximately one in three fetuses with persistent moderate/severe hydronephrosis
      required postnatal surgery. Overall, only one in every 1000 total births in the
      study population required postnatal urological surgery. CONCLUSIONS: The current
      study highlights the natural history of antenatally detected hydronephrosis. Mild
      fetal hydronephrosis appears to be associated with an excellent prognosis and
      probably represents the group with physiological renal pelvic dilatation.
      Moderate/severe fetal hydronephrosis is associated with poorer outcome and is
      perhaps the group that will need more intense follow up both antenatally and
      postnatally.

PMID- 11309167
TI  - The association of aneuploidy and mild fetal pyelectasis in an unselected
      population: the results of a multicenter study.
AB  - INTRODUCTION: Mild pyelectasis is a common finding and there is some debate as to
      its association with aneuploidy. The results of a large, prospective, multicenter
      study of mild pyelectasis designed to determine the incidence and association
      with aneuploidy in an unselected population are reported. METHODS: A large
      multicenter, prospective observational study of unselected fetuses with mild
      pyelectasis identified between 16 and 26 weeks' gestation in routine ultrasound
      departments. RESULTS: There were 737 fetuses with mild pyelectasis of which 12
      had an abnormal karyotype. Pyelectasis was isolated in three fetuses with Down
      syndrome, but in one the mother was older (36 years). CONCLUSION: These data
      confirm the fact that the presence of mild fetal pyelectasis increases the risk
      for aneuploidy, in particular trisomy 21. However, other risk factors should be
      considered before embarking on fetal karyotyping, as for most pregnancies
      complicated by isolated mild pyelectasis, risks of aneuploidy will remain small.

PMID- 11309168
TI  - Quantitative digital analysis of regional placental perfusion using power Doppler
      in placental abruption.
AB  - PURPOSE: To apply digital imaging techniques to the quantification of placental
      vascularity using power Doppler. MATERIALS AND METHODS: Regional placental blood
      flow was measured in a case of large placental abruption, shortly after
      presentation and 1 week later. Images were stored digitally and analysed using
      purpose-designed software (CQ Analysis) to extract and measure vascular energy
      information. The integrated color energy (ICE) was determined in the main body of
      placental tissue and in a cotyledon isolated by the retroplacental clot. RESULTS:
      Initial assessment at 25 weeks showed only a small difference in integrated
      energy between normal placenta and the isolated cotyledon (ICE ratio 1.44, P <
      0.04). One week later, perfusion in the isolated cotyledon had fallen both on
      qualitative and quantitative assessment (ICE ratio 3.98, P < 0.0001). This area
      subsequently became devascularized. CONCLUSION: Placental perfusion may be
      quantified using digital power Doppler analysis. Further studies are indicated to
      evaluate its role in assessing regional and/or global placental perfusion as well
      as fetal organ perfusion.

PMID- 11309169
TI  - Outcome of first-trimester chorionic villus sampling for genetic investigation in
      multiple pregnancy.
AB  - OBJECTIVES: To evaluate the efficacy of and risk associated with chorionic villus
      sampling for genetic investigations in multiple pregnancies, and to evaluate the
      accuracy of the ultrasonographic detection of chorionicity during the first
      trimester. PATIENTS AND METHODS: A total of 198 sets of twins and nine sets of
      triplets from 10 087 consecutive first-trimester pregnancies undergoing chorionic
      villus sampling were considered. Gestational age ranged from 7 to 12.6 weeks.
      Assessment and confirmation of chorionicity was based on a multiplicity of
      features. Dichorionicity was established in 169 sets of twins (85.3%) and
      trichorionicity in all triplet cases, while 29 twins were considered
      monochorionic. Chorionic villus sampling was performed transabdominally in all
      but one case, and identification of the placental insertion of the umbilical cord
      was the main benchmark for sampling. Sampling risks were evaluated by comparing
      clinical outcome with that of a control population of 63 dichorionic twin
      pregnancies which underwent no invasive procedure. RESULTS: Determination of the
      presence or absence of the lambda sign led to a correct assignment of
      chorionicity in all cases, while the presence of a membrane thickness of 2 mm or
      more reflected a 100% specificity with a 22% false negative rate. Sampling was
      successfully performed in all cases and in only four cases (1.0%) were two needle
      insertions needed. At follow-up no evidence of incorrect sampling was reported.
      Karyotyping was provided to all patients, and in 94.1% of cases both short and
      long-term culture methods were carried out. No difference in fetal and perinatal
      losses between the study and control populations was found, but a higher rate of
      deliveries before 37 weeks and of low birth weight babies was noted amongst
      controls. CONCLUSIONS: Chorionicity in twin pregnancy can be determined with
      certainty between 7 and 12 weeks of gestation; in cases of confluent placentas
      reliability is provided by determining the presence or absence of the lambda
      sign. This study indicates that first-trimester transabdominal chorionic villus
      sampling is a highly efficient, reliable, and relatively safe approach for
      genetic diagnosis in twin pregnancies. Although a precise evaluation of the
      relative risks of chorionic villus sampling and mid-trimester amniocentesis in
      twins must await randomized control studies, the advantages of a first-trimester
      diagnosis to enable early decision-making about selective fetal reduction are
      obvious.

PMID- 11309170
TI  - Cervical assessment at the routine 23-week scan: standardizing techniques.
AB  - OBJECTIVE: To examine the frequency of curvature of the cervix and to establish
      the degree of curvature with increasing cervical length. To assess the
      significance of this phenomenon in terms of the classification of patients as
      high risk for pre-term delivery. METHOD: Cervical length was measured
      prospectively by transvaginal sonography in 301 women at 23 weeks of gestation.
      The distance between the internal and external os was measured both as a straight
      line and also as a curved line along the endocervical canal. In addition, a
      search of our database was made to identify all women who had undergone cervical
      assessment as part of a policy of routine screening. In those with cervical
      length of less than 26 mm the thermal images of the cervix were used to obtain
      straight and curved measurements. The frequency of curved cervix was calculated
      and the relationship between the ratio of straight to curved measurement to the
      curved one was determined. RESULTS: In the prospective study curvature of the
      cervix was observed in 143 (48%) of the 301 women. Curvature was observed in 51%
      (135 of 267) with cervical length of 26-55 mm, 25% (8 of 32) with length of 16-25
      mm, and none of the two with length of 1-15 mm. The ratio of the straight to the
      curved measurement decreased with increasing cervical length (r = -0.27, P =
      0.001). In the retrospective study curvature of the cervix was found in 72 (15%)
      of 471 with length of 16-25 mm and in none of the 76 with length of 1-15 mm.
      CONCLUSION: Cervical length is influenced by the degree of cervical curvature.
      The disparity of measurements between the internal and external os taken as a
      straight line or along the cervical canal increases with cervical length.
      However, this disparity may not have any clinical implications because at short
      cervical length (less than 16 mm) the cervix appears to be always straight.

PMID- 11309171
TI  - Assessment of endothelial function in normal twin pregnancy.
AB  - OBJECTIVE: To assess the maternal endothelial function in normal twin pregnancy.
      DESIGN: Cross-sectional study. SUBJECTS: Endothelial function was investigated in
      74 women with normal twin pregnancy at 11-30 weeks of gestation and the results
      were compared to previous reported findings in 98 women with normal singleton
      pregnancy and 19 non-pregnant controls. METHODS: Endothelial function was
      assessed by measuring the changes of the brachial artery diameter in response to
      reactive hyperemia (flow-mediated dilatation) using external high resolution
      ultrasound. RESULTS: Flow-mediated dilatation of the brachial artery in both twin
      and singleton pregnancies was significantly higher than in non-pregnant women (P
      = 0.002 and P = 0.02, respectively). However, there was no significant difference
      in flow-mediated dilatation between women with twin and singleton pregnancy (9.61
      +/- 4.36 vs. 8.84 +/- 3.18, P = 0.38). Resting vessel size, baseline flow and
      reactive hyperemia did not change significantly with gestation in twin pregnancy
      and were similar to values in singleton pregnancies and controls. CONCLUSION: Our
      findings indicate that although in pregnancy endothelial function is enhanced,
      this change may not be affected by the number of fetoplacental units present.

PMID- 11309172
TI  - Umbilical vein blood flow in fetuses with normal and lean umbilical cord.
AB  - OBJECTIVE: To evaluate whether umbilical vascular coiling is correlated with the
      umbilical vein blood flow profile and to investigate if this is different between
      fetuses with a lean and those with a normal umbilical cord. METHODS: Consecutive
      women with a singleton gestation who delivered at term and who underwent an
      ultrasound examination within 24 h from delivery were studied. Umbilical cord and
      vessel areas were calculated. Umbilical vein blood flow parameters were obtained
      by digital color Doppler velocity profile integration. After delivery, the
      umbilical coiling index was calculated. RESULTS: One hundred and sixteen women
      were studied. Twelve (10.3%) had a lean umbilical cord (area < 10th centile). A
      significant correlation was found between the umbilical coiling index and the
      umbilical vein blood flow (r = 0.67, P < 0.001). A significant difference between
      fetuses with and without a lean cord was found in terms of: umbilical coiling
      index (0.18 +/- 0.08 vs. 0.29 +/- 0.09, P < 0.005), cord area (87.6 +/- 5.1 mm2
      vs. 200.6 +/- 34.6 mm2, P < 0.001), Wharton's jelly amount (25.7 +/- 10.3 mm2 vs.
      122.1 +/- 33.4 mm2, P < 0.001), umbilical vein blood flow (93.7 +/- 17.8 ml/kg
      per min vs. 126.0 +/- 23.4 ml/kg per min, P < 0.001), and umbilical vein blood
      flow mean velocity (6.6 +/- 2.7 cm/s vs. 9.0 +/- 3.6 cm/s, P < 0.05). The
      proportion of fetuses with an umbilical vein blood flow < 80 ml/kg per min was
      higher when the cord was lean than when it was normal (25% vs. 1.9%, P < 0.01).
      CONCLUSIONS: Lean umbilical cords differ from normal cords not only from a
      structural point of view but also in the umbilical vein blood flow
      characteristics. This could explain the increased incidence of intrapartum
      complications and fetal growth restriction among fetuses with a lean and/or
      hypocoiled cord.

PMID- 11309173
TI  - Influence of acupuncture on Doppler ultrasound in pregnant women.
AB  - OBJECTIVE: To evaluate the influence of acupuncture on the blood flow in the
      umbilical artery (UA), fetal aorta and uterine artery and on the fetal heart rate
      using two different acupuncture points (SP-6 (Sanyinjiao) and LI-4 (Hegu)).
      METHODS: In group A (n = 50), measurements (Doppler ultrasound and fetal heart
      rate) were performed at term after an uneventful pregnancy (#1) followed by
      acupuncture treatment using the acupuncture-point SP-6 bilaterally. The treatment
      time lasted 15 min after which the next measurement (#2) was carried out. The
      needles were then inserted into the LI-4 acupuncture point for a further 15 min.
      A third measurement at the end of acupuncture treatment (#3) completed the
      session. In group B (n = 25), measurements were made before (#1) and after (#4)
      acupuncture at LI-4 acupuncture points only. RESULTS: In group A, the mean
      systolic/diastolic (S/D) ratios of UA #1, UA #2 and UA #3 were 2.45, 2.38 and
      2.22, respectively (P = 0.0012). The difference in mean S/D ratios between UA #1
      and UA #3 as well as that between UA #2 and UA#3 were statistically significant
      (P = 0.0002 and P = 0.008, respectively). There was no difference between the
      mean S/D ratios of the uterine artery and between the mean resistance indices of
      the fetal aorta. In group B, the only significant difference between measurements
      following acupuncture treatment was in fetal heart rate (139 vs. 143 bpm, P =
      0.02). CONCLUSION: Our study indicates a positive influence of acupuncture
      treatment on umbilical artery waveforms when using a combination of SP-6
      (Sanyinjiao) and LI-4 (Hegu) acupuncture points. Acupuncture performed at these
      sites either individually or in combination does not seem to affect blood flow in
      the fetal aorta or uterine artery.

PMID- 11309174
TI  - Transvaginal power Doppler findings in laparoscopically proven acute pelvic
      inflammatory disease.
AB  - OBJECTIVES: To evaluate the usefulness of power Doppler transvaginal sonography
      (TVS) in the diagnosis of pelvic inflammatory disease (PID) and to assess the
      diagnostic reliability of specific sonographic findings. POPULATION: The study
      population consisted of 30 women admitted for suspected acute PID. The reference
      group consisted of 20 women with proven hydrosalpinx formation. METHODS: Both
      conventional TVS and power Doppler TVS were performed. All patients with
      suspected acute PID underwent laparoscopy in order to confirm the diagnosis.
      Sonographic criteria described earlier were used for the diagnosis of acute PID.
      Power Doppler was used to assess the vascularity of any adnexal mass. RESULTS:
      Laparoscopy confirmed the diagnosis of PID in 20 (67%) of the 30 women with
      clinically suspected acute PID. Specific TVS findings, including wall thickness >
      5 mm, cog-wheel sign, incomplete septa, and the presence of cul-de-sac fluid,
      discriminated women with acute PID from the control women with hydrosalpinx
      formation. Power Doppler TVS revealed hyperemia in all women with acute PID, but
      in only two women with hydrosalpinx (P = 0.01). Pulsatility indices were
      significantly lower in the acute PID group than in the control group (pulsatility
      index 0.84 +/- 0.04 vs. 1.50 +/- 0.10; P < 0.01). CONCLUSION: Power Doppler TVS
      was 100% sensitive and 80% specific in the diagnosis of PID (overall accuracy
      93%). Specific sonographic landmark findings and power Doppler findings augment
      the clinical diagnosis of PID and allow simple classification of the severity of
      the disease.

PMID- 11309175
TI  - Subendometrial contractility is not predictive for in vitro fertilization (IVF)
      outcome.
AB  - OBJECTIVES: The aim of the study was to investigate whether endometrial
      thickness, endometrial pattern, endometrial movement and serum estradiol and
      progesterone affect the outcome of in vitro fertilization. METHODS: Prospectively
      collected data of endometrial thickness, endometrial pattern and subendometrial
      activity were analyzed in 122 consecutive in vitro fertilization cycles. All
      measurements were made on the day of hCG administration (day -2), day of embryo
      transfer (day +2), day +6 and day +12. RESULTS: It would appear that pregnant
      women tend to have a thicker endometrium on day +12 than non-pregnant women.
      There appears to be no appreciable difference between pregnant and non-pregnant
      women in endometrial movement and thickness, nor in serum estradiol and
      progesterone on day +2 and day +6. In combining three echographic variables
      (thickness, pattern and movement) and hormone level (estradiol and progesterone),
      only progesterone on day +12 could be used to predict the outcome. CONCLUSIONS:
      Subendometrial contractility plays no important role in implantation on the day
      of embryo transfer or 4 days later.

PMID- 11309176
TI  - Sonography and neuropathology of a congenital brain tumor: report of a rare
      incident.
AB  - A rare case of a congenital brain tumor was diagnosed by sonography in a fetus at
      33 weeks' gestation. The ultrasound examination showed a large area of both
      increased echogenicity and echolucency in one hemisphere suggestive of brain
      tumor or hemorrhage. The neuropathological examination revealed an
      undifferentiated glial tumor with large areas of necrosis.

PMID- 11309177
TI  - Familial recurrence of spontaneous fetal intracranial hemorrhage:
      ultrasonographic diagnosis and postnatal magnetic resonance imaging (MRI).
AB  - We report fetal intracranial hemorrhage in term siblings from consanguineous
      parents, spontaneously occurring in the third trimester of pregnancy. Prenatal
      ultrasound in one case and postnatal MRI in both demonstrated massive parenchymal
      bleeding involving large areas of the cerebral cortex, white and gray matter.
      Vasculopathies, vascular malformations, coagulopathies, thrombocytopenia and
      relevant metabolic disorders could be excluded.

PMID- 11309178
TI  - Antenatal ultrasonographic features of fetal giant hemangiolymphangioma.
AB  - A giant multiseptate cystic mass covering the whole left hemitruncus of fetus was
      detected by ultrasonography at 23 weeks of gestation. Color and pulsed Doppler
      ultrasonography revealed marked blood flow in the mass. No other anomaly or
      chromosomal abnormality was recognized. Although the cystic lesion increased in
      size with advancing gestation a male infant weighing 4096 g was delivered in good
      condition at term. Histological examination of the lesion demonstrated
      hemangiolymphangioma with hyperplasia of both capillaries and lymphoducts. The
      infant was treated effectively with OK-432 and interferon-alfa-2a.

PMID- 11309179
TI  - Bilateral congenital diaphragmatic hernia: diagnostic clues at fetal sonography.
AB  - Bilateral congenital diaphragmatic hernia is a rare, life-threatening
      malformation. We describe a case of bilateral Bochdalek hernia diagnosed
      prenatally. The sonographic clues to the diagnosis were anterior displacement of
      the heart with relatively minimal lateral shift. The definitive diagnosis was
      made by demonstrating the liver in the right thorax and bowel loop and stomach in
      the left thorax. Color and power Doppler demonstrated the hepatic vessels
      embracing both sides of the heart from behind.

PMID- 11309180
TI  - Prenatal diagnosis of fetal ovarian hyperstimulation.
AB  - A case of prenatal diagnosis of fetal ovarian hyperstimulation in a pregnancy of
      35 weeks is reported. Two large cystic septate ovaries with no internal
      vegetations were observed in the fetal abdomen. The fetus was macrosomic and the
      remaining morphology was normal. Polyhydramnios and placental thickening were
      present, with no other macro- or microscopic alterations. The only significant
      maternal change detected was elevation of blood beta-human chorionic gonadotropin
      (beta-hCG) levels. Evaluation of the newborn confirmed the prenatal diagnosis,
      with progressive and spontaneous regression of fetal ovarian volume and of
      maternal serum beta-hCG occurring after delivery.

PMID- 11309181
TI  - Prenatal diagnosis of familial absent pulmonary valve syndrome: case report and
      review of the literature.
AB  - We report on a case of absent pulmonary valve syndrome in a woman with a history
      of one healthy child and one child with tetralogy of Fallot with absent pulmonary
      valve. The diagnosis was missed at the first ultrasound examination performed at
      13 + 5 weeks of gestation and correctly diagnosed at 21 + 5 weeks. Re-evaluation
      of the ultrasound examination recorded at 13 + 5 weeks exhibited severe
      insufficiency of the pulmonary valve at this time. However, neither dilatation of
      the right and left pulmonary arteries nor asymmetry of the ventricles were
      present at that time. The pregnancy was terminated at 22 + 1 weeks of gestation
      when autopsy confirmed the diagnosis of absent pulmonary valve syndrome.
      Karyotyping of the fetus after termination of pregnancy revealed normal
      chromosomes. Echocardiography of the parents and the healthy sibling revealed
      normal results.

PMID- 11309182
TI  - In utero diagnosis of obstructed supracardiac total anomalous pulmonary venous
      connection in a patient with right atrial isomerism and asplenia.
AB  - We describe a rare case of right atrial isomerism, levocardia, right-side
      stomach, obstructed supracardiac total anomalous pulmonary venous connection,
      double outlet right ventricle with complete atrioventricular septal defect and
      absent spleen. From the pulmonary venous confluence behind the atrium an
      ascending as well as a descending vertical vein communicated with the systemic
      venous system in the supracardiac as well as the infracardiac position. The
      pulsed and color Doppler examination of the individual pulmonary veins as well as
      of the vertical vein helped in making the diagnosis of obstructed total anomalous
      pulmonary venous connection. The diagnosis was made by fetal echocardiographic
      examination at 22 weeks of gestation and confirmed on postnatal echocardiography,
      cardiac catheterization, and at surgery.

PMID- 11309183
TI  - Second-trimester molecular diagnosis of a heterozygous 742 --> T (R248C) mutation
      in the FGFR3 gene in a thanatophoric dysplasia variant following suspicious
      ultrasound findings.

PMID- 11309184
TI  - Picture of the month. Transvaginal sonographic image of acute salpingitis.

PMID- 11309185
TI  - Effect of inner cannula removal on the work of breathing imposed by tracheostomy
      tubes: a bench study.
AB  - BACKGROUND: Tracheotomy has been used to assist in weaning patients from
      mechanical ventilation. Some patients fail to be weaned from the ventilator
      despite tracheostomy. We hypothesized that removing the inner cannula from the
      tracheostomy tube would decrease the tube's imposed work of breathing (WOB(IMP)).
      METHODS: The hypothesis was tested using a lung model, by measuring the change in
      WOB(IMP) when the inner cannula was removed. A mechanical lung model was
      developed using a test lung to simulate a spontaneously breathing patient.
      WOB(IMP) was measured with a commercially available lung mechanics monitor.
      Shiley size 6, 8, and 10 nonfenestrated tracheostomy tubes were tested with the
      inner cannula in and out. Breathing conditions were simulated using tidal volumes
      (V(T)) of 300 and 500 mL matched with breathing frequencies of 12, 24, and 32
      breaths per minute, by using a ventilator to simulate spontaneous breathing
      through one side of the test lung. RESULTS: Under all the tested breathing
      conditions, WOB(IMP) for each of the 3 tracheostomy tubes was significantly
      reduced (p < 0.05) when the inner cannula was removed. Also, as simulated
      spontaneous inspiratory flow demand increased (ie, as V(T) and/or frequency were
      increased), WOB(IMP) also increased, and vice versa. With the cannula removed,
      WOB(IMP) was not significantly different between the size 6 and 8 tubes nor
      between the size 8 and 10 tubes when V(T) was 300 mL and frequency was 12 breaths
      per minute. CONCLUSIONS: There was a significant decrease in WOB(IMP) with each
      tube when the inner cannula was removed. WOB(IMP) increased with an increase in
      inspiratory flow demand (ie, increase in V(T) and/or frequency), as well as when
      tube size decreased. In weaning a tracheostomized patient from mechanical
      ventilation, increasing the internal diameter of the tube by removing the inner
      cannula may be beneficial. Further study is needed to determine if these findings
      are clinically important.

PMID- 11309186
TI  - Electrical stimulation for swallowing disorders caused by stroke.
AB  - BACKGROUND: An estimated 15 million adults in the United States are affected by
      dysphagia (difficulty swallowing). Severe dysphagia predisposes to medical
      complications such as aspiration pneumonia, bronchospasm, dehydration,
      malnutrition, and asphyxia. These can cause death or increased health care costs
      from increased severity of illness and prolonged length of stay. Existing
      modalities for treating dysphagia are generally ineffective, and at best it may
      take weeks to months to show improvement. One common conventional therapy,
      application of cold stimulus to the base of the anterior faucial arch, has been
      reported to be somewhat effective. We describe an alternative treatment
      consisting of transcutaneous electrical stimulation (ES) applied through
      electrodes placed on the neck. OBJECTIVE: Compare the effectiveness of ES
      treatment to thermal-tactile stimulation (TS) treatment in patients with
      dysphagia caused by stroke and assess the safety of the technique. METHODS: In
      this controlled study, stroke patients with swallowing disorder were alternately
      assigned to one of the two treatment groups (TS or ES). Entry criteria included a
      primary diagnosis of stroke and confirmation of swallowing disorder by modified
      barium swallow (MBS). TS consisted of touching the base of the anterior faucial
      arch with a metal probe chilled by immersion in ice. ES was administered with a
      modified hand-held battery-powered electrical stimulator connected to a pair of
      electrodes positioned on the neck. Daily treatments of TS or ES lasted 1 hour.
      Swallow function before and after the treatment regimen was scored from 0
      (aspirates own saliva) to 6 (normal swallow) based on substances the patients
      could swallow during a modified barium swallow. Demographic data were compared
      with the test and Fisher exact test. Swallow scores were compared with the Mann
      Whitney U test and Wilcoxon signed-rank test. RESULTS: The treatment groups were
      of similar age and gender (p > 0.27), co-morbid conditions (p = 0.0044), and
      initial swallow score (p = 0.74). Both treatment groups showed improvement in
      swallow score, but the final swallow scores were higher in the ES group (p >
      0.0001). In addition, 98% of ES patients showed some improvement, whereas 27% of
      TS patients remained at initial swallow score and 11% got worse. These results
      are based on similar numbers of treatments (average of 5.5 for ES and 6.0 for TS,
      p = 0.36). CONCLUSIONS: ES appears to be a safe and effective treatment for
      dysphagia due to stroke and results in better swallow function than conventional
      TS treatment.

PMID- 11309187
TI  - Partnering for optimal respiratory home care: physicians working with respiratory
      therapists to optimally meet respiratory home care needs.
AB  - The need for respiratory care services continues to increase, reimbursement for
      those services has decreased, and cost-containment measures have increased the
      frequency of home health care. Respiratory therapists are well qualified to
      provide home respiratory care, reduce misallocation of respiratory services,
      assess patient respiratory status, identify problems and needs, evaluate the
      effect of the home setting, educate the patient on proper equipment use, monitor
      patient response to and complications of therapy, monitor equipment functioning,
      monitor for appropriate infection control procedures, make recommendations for
      changes to therapy regimen, and adjust therapy under the direction of the
      physician. Teamwork benefits all parties and offers cost and time savings,
      improved data collection and communication, higher job satisfaction, and better
      patient monitoring, education, and quality of life. Respiratory therapists are
      positioned to optimize treatment efficacy, maximize patient compliance, and
      minimize hospitalizations among patients receiving respiratory home care.

PMID- 11309188
TI  - Lung collapse during low tidal volume ventilation in acute respiratory distress
      syndrome.

PMID- 11309190
TI  - An AAA family tree.

PMID- 11309191
TI  - Compartmentalization of Ras proteins.
AB  - The Ras GTPases operate as molecular switches that link extracellular stimuli
      with a diverse range of biological outcomes. Although many studies have
      concentrated on the protein-protein interactions within the complex signaling
      cascades regulated by Ras, it is becoming clear that the spatial orientation of
      different Ras isoforms within the plasma membrane is also critical for their
      function. H-Ras, N-Ras and K-Ras use different membrane anchors to attach to the
      plasma membrane. Recently it has been shown that these anchors also act as
      trafficking signals that direct palmitoylated H-Ras and N-Ras through the
      exocytic pathway to the cell surface but divert polybasic K-Ras around the Golgi
      to the plasma membrane via an as yet-unidentified-route. Once at the plasma
      membrane, H-Ras and K-Ras operate in different microdomains. K-Ras is localized
      predominantly to the disordered plasma membrane, whereas H-Ras exists in a GTP
      regulated equilibrium between disordered plasma membrane and cholesterol-rich
      lipid rafts. These observations provide a likely explanation for the increasing
      number of biological differences being identified between the otherwise highly
      homologous Ras isoforms and raise interesting questions about the role membrane
      microlocalization plays in determining the interactions of Ras with its effectors
      and exchange factors.

PMID- 11309192
TI  - KSR: a MAPK scaffold of the Ras pathway?
AB  - Kinase Suppressor of Ras (KSR) is an intriguing component of the Ras pathway that
      was first identified by genetic studies performed in Drosophila melanogaster and
      Caenorhabditis elegans. In both organisms, inactivating mutations in KSR suppress
      the phenotypic effects induced by activated Ras. These findings together with the
      fact that KSR contains many structural features characteristic of a protein
      kinase led to early speculation that KSR is a kinase functioning upstream of the
      Ras pathway component Raf-1 or in a parallel Ras-dependent pathway. However, in
      the six years since its discovery, KSR has been found to lack several key
      properties of known protein kinases, which has cast doubt on whether KSR is
      indeed a functional enzyme. A major breakthrough in our understanding of the role
      of KSR in signal transduction has come from recent findings that KSR interacts
      with several components of the MAP kinase cascade, including Raf-1, MEK1/2 and
      ERK1/2. The model now emerging is that KSR acts as a scaffolding protein that
      coordinates the assembly of a membrane-localized, multiprotein MAP kinase
      complex, a vital step in Ras-mediated signal transduction. Thus, while Kinase
      Suppressor of Ras may be its name, phosphorylation may not be its game.

PMID- 11309193
TI  - Regulation of heparan sulfate proteoglycan nuclear localization by fibronectin.
AB  - Heparan sulfate proteoglycans (HSPG) regulate multiple cellular processes and
      mediate the cellular uptake of numerous molecules. While heparan sulphate
      glycosaminoglycan chains are known to modulate receptor binding of several
      heparin-binding proteins, here we show that distinct extracellular matrices
      direct HSPG to the nucleus. We analyzed HSPG localization in primary corneal
      fibroblasts, cultured on fibronectin or collagen type I matrices, using confocal
      laser scanning microscopy and cell fractionation. Image analysis revealed that
      the nuclear localization of HSPG core proteins was greater when cells were
      cultured on fibronectin versus collagen. Matrices containing the heparin-binding
      domain of fibronectin, but not the integrin-activating domain, demonstrated
      increased nuclear staining of core proteins. Furthermore, activation of protein
      kinase C with phorbol 12-myristate 13-acetate inhibited nuclear targeting of HSPG
      in cells on fibronectin, whereas inhibition of protein kinase C with Ro-31-8220
      greatly enhanced nuclear localization of HSPG in cells on both collagen and
      fibronectin. We propose a matrix-dependent mechanism for nuclear localization of
      cell surface HSPG involving protein kinase C-mediated signaling. Nuclear
      localization of HSPG might play important roles in regulating nuclear function.

PMID- 11309194
TI  - Peroxisomal targeting of mammalian hydroxyacid oxidase 1 requires the C-terminal
      tripeptide SKI.
AB  - Peroxisomal proteins are post-translationally imported into peroxisomes after
      recognition by specific receptors. The best-defined peroxisomal targeting signal
      is a C-terminal tripeptide SKL. Different functional variants of this tripeptide
      have been defined, but mutants with a SKI sequence were recognized as being
      inefficiently targeted to peroxisomes. Recently, we have cloned a cDNA for the
      mouse hydroxyacid oxidase 1 (Hao1), a protein that seems to be localized in
      peroxisomes. Interestingly, the mouse Hao1 sequence comprises a C-terminal SKI
      tripeptide. We have analyzed the subcellular localization of Hao1 and tested
      whether its SKI sequence acts as a targeting signal. Ltk(-) and Cos-7 cells were
      transfected with vectors expressing a fusion protein of green fluorescence
      protein and Hao1, as well as mutants thereof. Targeting to peroxisomes of the
      fusion protein with the wild-type SKI sequence was highly selective and as
      complete as with the peroxisome-specific SKL sequence. By contrast, targeting was
      lost in a mutant with the sequence CKM. The data show that mammalian Hao1 is a
      peroxisomal protein and that the C-terminal sequence SKI acts as the targeting
      signal.

PMID- 11309195
TI  - Overexpression of the Csk homologous kinase (Chk tyrosine kinase) induces
      multinucleation: a possible role for chromosome-associated Chk in chromosome
      dynamics.
AB  - The Csk family of non-receptor-type tyrosine kinases consists of Csk and the Csk
      homologous kinase Chk. Each enzyme suppresses the catalytic activity of Src
      family kinases by phosphorylating their C-terminal negative regulatory tyrosine
      residues. Ectopic and transient expression of Chk in COS-1 cells showed nuclear
      localization of Chk and growth inhibition. To further explore the role of Chk in
      cell growth, we overexpressed Chk in human immature myeloid KMT-2 cells. Chk
      overexpression brought about growth retardation and aberrant chromosome movement
      leading to multinucleation, and these events were accompanied by insufficient
      formation of mitotic spindles. In vitro kinase assays showed that Chk
      overexpression suppressed the tyrosine kinase activity of Lyn, a member of the
      Src family, immunoprecipitated from Triton X-100 lysates. Subcellular
      fractionation studies revealed that fractions of Chk and Lyn, resistant to Triton
      X-100 solubilization, are associated with mitotic chromosome scaffolds and
      spindles. Chk overexpression induced a decrease in autophosphorylation of Lyn and
      concomitant changes in levels of tyrosine phosphorylation of proteins associated
      with both fractions. These results indicate that Chk, Lyn and the tyrosine
      phosphorylated proteins localize to mitotic chromosomes and spindles, suggesting
      that Chk-dependent tyrosine phosphorylation, presumably through Lyn, may be
      involved in chromosome dynamics.

PMID- 11309196
TI  - Potential role of nuclear translocation of glyceraldehyde-3-phosphate
      dehydrogenase in apoptosis and oxidative stress.
AB  - Recent studies indicating a role of glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) in apoptosis or oxidative stress has been reported. Using confocal laser
      scanning microscopy, we have investigated the cellular distribution of GAPDH in
      central nervous system (CNS)-derived cells (neuroblastoma mNB41A3), in non-CNS
      derived cells (R6 fibroblast) and in an apoptosis-resistant Bcl2 overexpressing
      cell line (R6-Bcl2). Induction of apoptosis by staurosporine or MG132 and
      oxidative stress by H(2)O(2) or FeCN enhanced the nuclear translocation of
      endogenous GAPDH in all cell types, as detected by immunocytochemistry. In
      apoptotic cells, GAPDH expression is three times higher than in non-apoptotic
      cells. Consistent with a role for GAPDH in apoptosis, overexpression of a GAPDH
      green fluorescent protein (GAPDH-GFP) hybrid increased nuclear import of GAPDH
      GFP into transfected cells and the number of apoptotic cells, and made them more
      sensitive to agents that induce apoptosis. Bcl2 overexpression prevents nuclear
      translocation of GAPDH and apoptosis in untransfected cells, but not in
      transfected cells that overexpress GAPDH-GFP. Our observations indicate that
      nuclear translocation of GAPDH may play a role in apoptosis and oxidative stress,
      probably related to the activity of GAPDH as a DNA repair enzyme or as a nuclear
      carrier for pro-apoptotic molecules.

PMID- 11309197
TI  - Apoptotic cell death of cultured salamander photoreceptors induced by cccp: CsA
      insensitive mitochondrial permeability transition.
AB  - Photoreceptor degeneration is mediated by apoptosis in several animal models,
      although the underlying mechanisms are yet to be elucidated. We present here an
      apoptotic model based on a primary cell culture of tiger salamander
      photoreceptors, in which treatment with carbonyl cyanide m-chlorophenylhydrazone
      (cccp), a protonophore, induced apoptosis. Cells exposed to cccp showed condensed
      nuclei and displayed positive TdT-dUTP terminal nick-end labeling (TUNEL). In
      addition, 10-100 microM cccp rapidly induced a reduction of Delta psi(m) and > or
      = 30 microM cccp induced a significant leakage of calcein from mitochondria to
      cytosol and nucleus, indicating a change in mitochondrial inner membrane
      permeability. Cyclosporin A (CsA), a transition pore blocker, did not prevent the
      cccp-induced MPT or the cccp-evoked apoptotic cell death, suggesting that cccp
      induced apoptotic process was mediated by a CsA-insensitive pathway. This cell
      model provides an in vitro tool for studying mechanisms of photoreceptor
      apoptosis in isolated photoreceptors and may provide clues to the etiology of
      retinal degeneration.

PMID- 11309198
TI  - A putative, ubiquitin-dependent mechanism for the recognition and elimination of
      defective spermatozoa in the mammalian epididymis.
AB  - The normal structure and function of sperm are prerequisites for successful
      fertilization and embryonic development, but little is known about how defective
      sperm are eliminated during mammalian spermatogenesis. Here, we describe a
      ubiquitin-dependent, sperm quality control mechanism that resides in the
      mammalian epididymis, the site of sperm maturation and storage. We used
      immunofluorescence, electron microscopy, western blotting and pulse-chase
      experiments to show that ubiquitin is secreted by the epididymal epithelium and
      binds to the surface of defective sperm. Most of the ubiquitinated sperm are
      subsequently phagocytosed by the epididymal epithelial cells. A portion of
      defective sperm escapes phagocytosis and can be found in the ejaculate. Cultured
      epididymal cells maintain their ability to produce ubiquitin and phagocytose the
      defective sperm, as well as the ubiquitin-coated microspheres, in vitro. The
      surprising phenomenon of cell-surface ubiquitination in defective sperm provides
      a possible mechanism for sperm quality control in mammals and a new marker of
      semen abnormalities in men and animals.

PMID- 11309199
TI  - The WD protein Rack1 mediates protein kinase C and integrin-dependent cell
      migration.
AB  - The scaffolding protein, Rack1, is a seven-WD-domain-containing protein that has
      been implicated in binding to integrin beta subunit cytoplasmic domains and to
      members of two kinase families (src and protein kinase C, PKC) that mediate
      integrin bidirectional signaling. To explore the role of Rack1 in integrin
      function we have transfected this protein in Chinese hamster ovary (CHO) cells.
      We have observed no effect of Rack1 overexpression on inside-out signaling as the
      ligand binding properties of CHO cells also expressing constitutively active or
      inactive integrins were not affected. In contrast, we observed that cells stably
      or transiently overexpressing Rack1 had decreased migration compared to mock
      transfected cells. Stable Rack1 transfectants also demonstrated an increased
      number of actin stress fibers and focal contacts. These effects on motility and
      cytoskeletal organization did not appear to result from Rack1 inhibition of src
      function as downstream substrates of this kinase were phosphorylated normally. In
      addition, expression of an active src construct did not reverse the migratory
      deficit induced by Rack1 overexpression. On the other hand when we overexpressed
      a Rack1 variant with alanine substitutions in the putative PKC binding site in
      its third WD domain, we observed no deficit in migration. Thus the ability of
      Rack1 to bind, localize and stabilize PKC isoforms is likely to be involved in
      aspects of integrin outside-in signaling.

PMID- 11309200
TI  - Phosphorylation of p190 on Tyr1105 by c-Src is necessary but not sufficient for
      EGF-induced actin disassembly in C3H10T1/2 fibroblasts.
AB  - p190 RhoGAP is a tyrosine phosphorylated protein that contains an N-terminal GTP
      binding domain, a middle domain (MD) that mediates interaction with p120 RasGAP
      and a C-terminal GTPase-activating protein (GAP) domain that is specific for the
      &Rgr; family of small GTPases. Evidence is accumulating to suggest that p190
      participates in actin cytoskeleton rearrangements that occur following
      transformation by v-Src or stimulation by growth factors, and that tyrosine
      phosphorylation of p190 by Src influences these processes. The current study was
      performed to establish whether p190RhoGAP directly participates in epidermal
      growth factor-induced actin stress fiber disassembly and how c-Src is involved in
      this process. Our results support a model in which the p190 MD negatively
      regulates the activity of the GAP domain and that c-Src phosphorylation of Y1105
      is necessary, but insufficient on its own, for actin stress fiber disassembly.

PMID- 11309201
TI  - Expression and localisation of synaptotagmin isoforms in endocrine beta-cells:
      their function in insulin exocytosis.
AB  - Exocytosis of insulin containing Large Dense Core Vesicles (LDCVs) from
      pancreatic beta-cells and derived cell lines is mainly controlled by Ca(2+).
      Several lines of evidence have demonstrated a role of the Ca(2+)- and
      phospholipid-binding protein synaptotagmin (syt) in this event. Synaptotagmins
      form a large protein family with distinct affinities for Ca(2+) determined by
      their two C(2) domains (C(2)A/B). Except for the well-characterized isoforms I
      and II, their role is still unclear. We have used here insulin-secreting cells as
      a model system for LDCV exocytosis to gain insight into the function of
      synaptotagmins. Immunocytochemical analysis revealed that of the candidate Ca(2+)
      sensors in LDCV exocytosis, syt III was not expressed in primary beta-cells,
      whereas syt IV was only found adjacent to the TGN. However, syt V-VIII isoforms
      were expressed at different levels in various insulin-secreting cells and in
      pancreatic islet preparations. In streptolysin-O permeabilized primary beta-cells
      the introduction of recombinant peptides (100 nM) corresponding to the C(2)
      domains of syt V, VII and VIII, but not of syt III, IV or VI, inhibited Ca(2+)
      evoked insulin exocytosis by 30% without altering GTP gamma S-induced release.
      Our observations demonstrate that syt III and IV are not involved in the
      exocytosis of LDCVs from primary beta-cells whereas V, VII and VIII may mediate
      Ca(2+)-regulation of exocytosis.

PMID- 11309202
TI  - Nucleocytoplasmic transport in human astrocytes: decreased nuclear uptake of the
      HIV Rev shuttle protein.
AB  - Astrocytes are cellular targets for the human immunodeficiency virus (HIV) that
      limit virus production, owing, at least in part, to the diminished functionality
      of the viral post-transcriptional stimulatory factor Rev. To understand the
      trafficking process in astrocytes, we compared nucleocytoplasmic transport of Rev
      and various proteins with well-characterized nucleocytoplasmic transport features
      in human astrocytes and control cells (HeLa). Localization and trafficking
      characteristics of several cellular and viral proteins, as well as nuclear
      trafficking of classical peptide signals upon microinjection were similar in both
      cell types, indicating maintenance of general features of nucleocytoplasmic
      transport in astrocytes. Quantification of fluorescence in living cells
      expressing Rev fused to green fluorescent protein (GFP) indicated a strong shift
      in intracellular distribution of Rev in astrocytes, with 50-70% of Rev in the
      cytoplasm, whereas the cytoplasmic proportion of Rev in HeLa cells is around 10%.
      The dynamics of nucleocytoplasmic trafficking of Rev were compared in astrocytes
      and Rev-permissive cells by monitoring migration of Rev-GFP in cell fusions using
      highly sensitive time-lapse imaging. Nuclear uptake of Rev was dramatically
      retarded in homo-polykaryons of astrocytes compared with control cells.
      Diminished nuclear uptake of Rev was also observed in hetero-polykaryons of Rev
      permissive cells and astrocytes. These results indicate that astrocytes contain a
      cytoplasmic activity that interferes with nuclear uptake of Rev. Our studies
      suggest a model in which Rev is prevented from functioning efficiently in
      astrocytes by specific alterations of its nucleocytoplasmic trafficking
      properties.

PMID- 11309203
TI  - RNA anchoring in the vegetal cortex of the Xenopus oocyte.
AB  - The body plan of the embryo is established by a polarized source of developmental
      information in the oocyte. The Xenopus laevis oocyte creates polarity by
      anchoring mRNAs in the vegetal cortex, including Vg1 and Xwnt-11, which might
      function in body plan specification, and Xcat-2, which might function in germ
      cell development. To identify components of the RNA anchoring mechanism, we used
      the manually isolated vegetal cortex (IVC) to assay loss or change in spatial
      arrangement of mRNAs caused by disruption of cortical elements. The role of
      cytoskeleton in mRNA anchoring was tested by treating oocytes with inhibitors
      that selectively disrupted actin microfilaments and cytokeratin filaments.
      Treatment of oocytes with cytochalasin B caused clumping of Vg1 and Xwnt-11 as
      revealed by in situ hybridization of the IVC, but did not cause their release, as
      confirmed by RT-PCR analysis. These mRNA clumps did not match the distribution of
      actin microfilament clumps, but were distributed similarly to the remnant
      cytokeratin filaments. Treatment of oocytes with monoclonal anti-cytokeratin
      antibody C11 released these mRNAs from the cortex. C11 altered the texture of the
      cytokeratin network, but did not affect the actin meshwork. These results show
      that Vg1 and Xwnt-11 are retained by a cytokeratin filament-dependent mechanism,
      and that organization of the cytokeratin network depend on an intact actin
      meshwork. Colcemid did not disrupt Vg1 and Xwnt-11 retention in the IVC, so
      anchoring of these mRNAs are independent of microtubules. Membrane disruption in
      the IVC by Triton X-100 decreased Vg1 and Xwnt-11. Loss of these mRNAs was due
      mainly to ribonuclease activity released from membrane components. However, when
      ribonuclease activity was suppressed under cold temperature, a higher amount of
      Vg1 and Xwnt-11 was recovered in the supernatant. This result suggested that a
      fraction of these mRNAs required membranes to be retained in the cortex. By
      contrast, Xcat-2 mRNA was neither released nor degraded following treatments with
      cytochalasin B, C11, colcemid and Triton X-100 under cold temperature, so no
      cortical element could be implicated in its anchoring.

PMID- 11309204
TI  - Self-assembly and binding of a sorting nexin to sorting endosomes.
AB  - The fate of endocytosed membrane proteins and luminal contents is determined by a
      materials processing system in sorting endosomes. Endosomal retention is a
      mechanism that traps specific proteins within this compartment, and thereby
      prevents their recycling. We report that a sorting nexin SNX1, a candidate
      endosomal retention protein, self-assembles in vitro and in vivo, and has this
      property in common with its yeast homologue Vps5p. A comparison of SNX1 expressed
      in bacterial and in mammalian systems and analyzed by size-exclusion
      chromatography indicates that in cytosol SNX1 tetramers are part of a larger
      complex with additional proteins. An endosomal retention function would require
      that SNX1 bind to endosomal membranes, yet the complexes that we analyzed were
      largely soluble and little SNX1 was found in pellet fractions. Using green
      fluorescent protein fusions, endocytic compartment markers and fluorescence
      recovery after photobleaching, we found that there is an equilibrium between free
      cytoplasmic and early/sorting endosome-bound pools of green fluorescent protein
      SNX1. Fluorescence resonance energy transfer indicated that spectral variants of
      green fluorescent protein-SNX1 were oligomeric in vivo. In cell extracts, these
      green fluorescent protein-SNX1 oligomers corresponded to tetrameric and larger
      complexes of green fluorescent protein-SNX1. Using video microscopy, we observed
      small vesicle docking and tubule budding from large green fluorescent protein
      SNX1 coated endosomes, which are features consistent with their role as sorting
      endosomes. http://www.biologists.com/JCS/movies/jcs2058.html

PMID- 11309205
TI  - Rabphilin dissociated from Rab3 promotes endocytosis through interaction with
      Rabaptin-5.
AB  - Rabphilin is a secretory vesicle protein that interacts with the GTP-bound form
      of the small GTPase Rab3. We investigated the involvement of Rabphilin in
      endocytosis using different point mutants of the protein. Overexpression of wild
      type Rabphilin in the insulin-secreting cell line HIT-T15 did not affect receptor
      mediated transferrin endocytosis. By contrast, Rabphilin V61A, a mutant that is
      unable to interact with Rab3, enhanced the rate of transferrin internalization.
      The effect of Rabphilin V61A was not mimicked by Rabphilin L83A, another mutant
      with impaired Rab3 binding. Careful analysis of the properties of the two mutants
      revealed that Rabphilin V61A and Rabphilin L83A are both targeted to secretory
      vesicles, have stimulatory activity on exocytosis, and bind equally well to alpha
      actinin. However, Rabphilin L83A fails to interact with Rabaptin-5, an important
      component of the endocytotic machinery. These results indicate that Rabphilin
      promotes receptor-mediated endocytosis and that its action is negatively
      modulated by Rab3. We propose that the hydrolysis of GTP that is coupled to the
      exocytotic event disrupts the Rabphilin-Rab3 complex and permits the recruitment
      of Rabaptin-5 at the fusion site. Our data show that immediately after
      internalization the transferrin receptor and VAMP-2 colocalize on the same
      vesicular structures, suggesting that Rabphilin favors the rapid recycling of the
      components of the secretory vesicle.

PMID- 11309206
TI  - Cholesterol requirement for cation-independent mannose 6-phosphate receptor exit
      from multivesicular late endosomes to the Golgi.
AB  - The regulation of endocytic traffic of receptors has central importance in the
      fine tuning of cell activities. Here, we provide evidence that cholesterol is
      required for the exit of cation-independent mannose 6-phosphate receptor (CI-MPR)
      from the endosomal carrier vesicle/multivesicular bodies (ECV/MVBs) to the Golgi.
      A previously established Chinese hamster ovary cell mutant, LEX2, exhibits
      arrested ECV/MVBs in which CI-MPR and lysosomal glycoprotein-B (lgp-B) are
      accumulated. The abnormal accumulation of CI-MPR within the ECV/MVBs in LEX2
      cells was corrected in a post-translational manner by the supplementation of
      medium with cholesterol. Furthermore, it was shown that, by expression cloning
      using LEX2 mutant, the introduction of the NAD(P)H steroid dehydrogenase-like
      protein, an enzyme involved in the later stage of cholesterol biosynthesis,
      allows the exit of CI-MPR from the MVBs to the Golgi and reduces the number of
      arrested ECV/MVBs in LEX2 cells. The recovery of the exit transport of CI-MPR
      from the ECV/MVBs was associated with the restoration of the normal cellular free
      cholesterol level and segregation between CI-MPR and lgp-B, both of which had
      been localized at the internal small vesicles of the arrested ECV/MVBs. By
      contrast, the restoration of cholesterol failed to correct the defective
      processing of endocytosed LDL to a degradative compartment in LEX2 cells. These
      results suggest that cholesterol is required for ECV/MVB reorganization that
      drives the sorting/transport of materials destined for the Golgi out of the
      pathways towards lysosomes.

PMID- 11309207
TI  - A single internalization signal from the di-leucine family is critical for
      constitutive endocytosis of the type II TGF-beta receptor.
AB  - Endocytosis has an important contribution to the regulation of the surface
      expression levels of many receptors. In spite of the central role of the
      transforming growth factor beta (TGF-beta) receptors in numerous cellular and
      physiological processes, their endocytosis is largely unexplored. Current
      information on TGF-beta receptor endocytosis relies exclusively on studies with
      chimeric constructs containing the extracellular domain of the GM-CSF receptors,
      following the internalization of the GM-CSF ligand; the conformation and
      interactions of the chimeric receptors (and therefore their endocytosis) may
      differ considerably from those of the native TGF-beta receptors. Furthermore,
      there are no data on the potential endocytosis motif(s) of the TGF-beta receptors
      or other receptor Ser/Thr kinases. Here, we report the use of type II TGF-beta
      receptors, myc-tagged at their extracellular terminus, to investigate their
      endocytosis. Employing fluorescent antibody fragments to label exclusively the
      cell surface myc-tagged receptors exposed to the external milieu, made it
      possible to follow the internalization of the receptors, without the
      complications that render labeling with TGF-beta (which binds to many cellular
      proteins) unsuitable for such studies. The results demonstrate that the full
      length type II TGF-beta receptor undergoes constitutive endocytosis via clathrin
      coated pits. Using a series of truncation and deletion mutants of this receptor,
      we identified a short peptide sequence (I(218)I(219)L(220)), which conforms to
      the consensus of internalization motifs from the di-leucine family, as the major
      endocytosis signal of the receptor. The functional importance of this sequence in
      the full-length receptor was validated by the near complete loss of
      internalization upon mutation of these three amino acids to alanine.

PMID- 11309208
TI  - Testase 1 (ADAM 24) a plasma membrane-anchored sperm protease implicated in sperm
      function during epididymal maturation or fertilization.
AB  - Plasma membrane-anchored proteases have key roles in cell signaling, migration
      and refashioning the cell surface and its surroundings. We report the first
      example of a plasma membrane-anchored protease on mature sperm, testase 1 (ADAM
      24). Unlike other studied sperm ADAMs (fertilin alpha and beta, cyritestin) whose
      metalloprotease domains are removed during sperm development, we found testase 1
      retains an active metalloprotease domain, suggesting it acts as a protease on
      mature sperm. Testase 1 is a glycoprotein (molecular mass 88 kDa), localized to
      the equatorial region of the plasma membrane of cauda epididymal sperm.
      Typically, proteolytic removal of the pro-domain is an initial activation step
      for ADAM proteases. The pro-domain of the testase 1 precursor (108 kDa) is
      proteolytically removed as sperm transit the caput epididymis to produce
      processed (mature) testase 1 (88 kDa). Testase 1 is unique among all studied
      ADAMs in that its proteolytic processing occurs on the sperm plasma membrane
      instead of at an intracellular site (the Golgi). Using GST-fusion proteins and a
      synthetic testase 1 C-terminal peptide, we found that the cytoplasmic tail of
      testase 1 could be phosphorylated in vitro by protein kinase C (PKC). Thus
      testase 1 apparently has a cytoplasmic PKC phosphorylation site(s). Protein
      kinase C is known to stimulate other ADAMs' protease activity. Because events of
      the acrosome reaction include PKC activation, we speculate that testase 1
      protease function could be important in sperm penetration of the zona pellucida
      after sperm PKC is activated during the acrosome reaction.

PMID- 11309209
TI  - Facilitating cancer pain control in the home: opioid-related issues.
AB  - The basic principles of pain management are the same whether the patient is in an
      acute care setting, their home, or a long-term care facility. Wherever the
      setting, pain management is part of the comprehensive care for the cancer
      patient. Successful therapy depends on a clear definition of treatment goals, an
      informed patient and family, collaboration and effective communication between
      the physician, home care nurse, patient and family, and ongoing monitoring to
      ensure effectiveness of pain relief measures. Careful discharge planning to
      ensure appropriate home care for the patient with pain and their family is
      critical.

PMID- 11309210
TI  - Antidepressants in the management of cancer pain.
AB  - Most patients who have been diagnosed with cancer will experience pain at some
      point during the course of their disease. Often, opioid analgesics are not enough
      to completely alleviate the patient's pain and the selection of appropriate
      adjunct analgesic agents is critical. This article reviews the mechanisms of
      action and analgesic effects of several classes of antidepressants to enable the
      clinician to select the appropriate agent for the patient.

PMID- 11309211
TI  - Management of opioid-induced constipation.
AB  - Constipation is an expected side effect of opioid use and as such should be
      treated prophylactically. However, because it is often overlooked and under
      appreciated it is one of the most common reasons patients avoid or abandon opioid
      use and, as a result, suffer pain needlessly. Thorough assessment, ongoing
      evaluation, and patient teaching are key factors in establishing an effective
      bowel regimen. A bowel clean-out is indicated for patients who have not had a
      bowel movement in more than 5 days. Once any impactions have been eliminated, a
      regular regimen of senna and docusate is recommended. Dietary modifications,
      fluids, and exercise are important but usually not sufficient to overcome opioid
      induced constipation. Although many of the medicines that are used to treat pain
      and related symptoms come with a significant potential for distressing side
      effects, it is important to understand that most side effects, especially
      constipation, can be managed and quality of life can be preserved without
      sacrificing needed analgesia.

PMID- 11309212
TI  - Neuraxial infusion in patients with chronic intractable cancer and noncancer
      pain.
AB  - Ever since the application in 1980 of morphine for spinal analgesia in patients
      with refractory cancer pain, spinal infusion therapy has become one of the
      cornerstones for the management of chronic, medically intractable pain.
      Initially, spinal infusion therapy was indicated only for patients with cancer
      pain that could not be adequately controlled with systemic narcotics. However,
      over the past decade, there has been a significant increase in the number of
      pumps implanted for the treatment of nonmalignant pain. Indeed, "benign" pain
      syndromes, particularly failed back surgery syndrome, are the most common
      indication for intrathecal opiates. As we have gained more experience with this
      therapy, it has become apparent that even intrathecal opiates, when administered
      in the long term, can be associated with problems such as tolerance,
      hyperalgesia, and other side effects. Consequently, long-term efficacy has not
      been as significant as had been hoped. Because of the difficulties associated
      with long-term intrathecal opiate therapy, much of the research, both basic and
      clinical, has focused on developing alternative nonopioid agents to be used
      either alone or in combination with opiates. Clinical trials have been and
      continue to be conducted to evaluate drugs such as clonidine, SNX-111, local
      anesthetics, baclofen, and many other less common agents to determine their
      efficacy and potential toxicity for intrathecal therapy. This article reviews the
      agents developed as alternatives to intrathecal opiates.

PMID- 11309213
TI  - Modern management of the cancer anorexia-cachexia syndrome.
AB  - The cancer anorexia-cachexia syndrome is common, occurring in 80% of patients
      with advanced-stage cancer, and it is one of the most frequent causes of death in
      patients with cancer. It is a complex problem involving abnormalities in protein,
      carbohydrate, and fat metabolism. Tumors have both direct and indirect effects
      that result in anorexia and weight loss. The disease burden does not necessarily
      correlate with the degree of cachexia. In addition to the physical
      manifestations, the resulting abnormalities have a significant psychologic effect
      on patients and their families. Although there is no treatment to reverse the
      process, pharmacologic and nonpharmacologic measures can enhance food intake and
      improve quality of life.

PMID- 11309214
TI  - Advances in cancer pain management.
AB  - Control of malignant pain and related symptoms is paramount to clinical success
      in caring for cancer patients. To achieve the best quality of life for patients
      and families, oncologists and palliative care clinicians must work together to
      understand problems related to psychologic, social, and spiritual pain. Pain is
      the primary problem targeted for control using the World Health Organization's
      (WHO) analgesic ladder. This article focuses on increased knowledge of analgesic
      action that may enable expansion of the WHO analgesic ladder to fulfill the
      broader objectives of palliative medicine. We discuss clinical experience with
      several classes of drugs that are currently used to treat cancer pain: 1)
      nonsteroidal anti-inflammatory drugs, with emphasis on cyclooxygenase-2
      inhibitors; 2) opioid analgesics, with specific emphasis on methadone and its
      newly recognized value in cancer pain; 3) ketamine, an antagonist at N-methyl-d
      aspartate receptors; and 4) bisphosphonates, used for pain resulting from bone
      metastases. New concepts that compare molecular actions of morphine at excitatory
      opioid receptors, and methadone at nonopioid receptor systems, are presented to
      underscore the importance of balancing central nervous system excitatory (anti
      analgesic) versus inhibitory (analgesic) influences.

PMID- 11309215
TI  - Symptoms and therapies: exertional and sexual headaches.
AB  - This article discusses the headache disorders associated with physical and sexual
      activity, highlighting their differences and similarities. The place of
      exertional and sexual headaches in the classification of the International
      Headache Society and in the proposed classification of Indomethacin-Responsive
      Headache Disorders is addressed here. The Valsalva's maneuver as a shared
      pathophysiologic mechanism is mentioned as well. Exertional headaches are divided
      into two subtypes, according to the pattern of physical exercises. Sexual
      headaches are divided into three subtypes, based on the onset time, related to
      orgasm. The clinical characteristics of each type are presented, and their
      etiologies pointed out. The diagnostic approach is discussed, as well as the
      nonpharmacologic and pharmacologic treatment options.

PMID- 11309216
TI  - The exploding head syndrome.
AB  - This article reviews the features of an uncommon malady termed "the exploding
      head syndrome." Sufferers describe terrorizing attacks of a painless explosion
      within their head. Attacks tend to occur at the onset of sleep. The etiology of
      attacks is unknown, although they are considered to be benign. Treatment with
      clomipramine has been suggested, although most sufferers require only reassurance
      that the spells are benign in nature.

PMID- 11309217
TI  - Postdural puncture headache: the role of prophylactic epidural blood patch.
AB  - Prophylactic epidural blood patch may prevent postdural puncture headache that
      develops after intentional or inadvertent dural puncture. However, despite
      earlier reports that this procedure was of value, subsequent studies have failed
      to show it has significant advantages over delayed blood patch. Reports that were
      supportive of this technique were based on nonrandomized observational studies
      with significant selective bias. At the present time, most centers do not
      routinely offer prophylactic blood patches, and those that do report a variable
      success rate. A recent case study of permanent neurologic deficit after
      prophylactic epidural blood patch has also raised some concern about the safety
      of this prophylactic technique.

PMID- 11309218
TI  - Spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension (SIH) is typically manifested by orthostatic
      headaches that may be associated with one or more of several other symptoms,
      including pain or stiffness of the neck, nausea, emesis, horizontal diplopia,
      dizziness, change in hearing, visual blurring or visual field cuts, photophobia,
      interscapular pain, and occasionally face numbness or weakness or radicular upper
      limb symptoms. Cerebrospinal fluid (CSF) pressures, by definition, are quite low.
      SIH almost invariably results from a spontaneous CSF leak. Only very infrequently
      is this leak at the skull base (cribriform plate). In the overwhelming majority
      of patients, the leak is at the level of the spine, particularly the thoracic
      spine and cervicothoracic junction. Sometimes, documented leaks and typical
      clinical and imaging findings of SIH are associated with CSF pressures that are
      consistently within limits of normal. Magnetic resonance imaging of the head
      typically shows diffuse pachymeningeal gadolinium enhancement, often with imaging
      evidence of sinking of the brain, and less frequently with subdural fluid
      collections, engorged cerebral venous sinuses, enlarged pituitary gland, or
      decreased size of the ventricles. Radioisotope cisternography typically shows
      absence of activity over the cerebral convexities, even at 24 or 48 hours, and
      early appearance of activity in the kidneys and urinary bladder, and may
      sometimes reveal the level of the leak. Although various treatment modalities
      have been implemented, epidural blood patch is probably the treatment of choice
      in patients who have failed an initial trial of conservative management. When
      adequate trials of epidural blood patches fail, surgery can offer encouraging
      results in selected cases in which the site of the leak has been identified. Some
      of the spontaneous CSF leaks are related to weakness of the meningeal sac, likely
      in connection with a connective tissue abnormality.

PMID- 11309220
TI  - The factors associated with disclosure of intimate partner abuse to clinicians.
AB  - OBJECTIVE: Our goal was to identify the prevalence, determinants of, and barriers
      to clinician-patient communication about intimate partner abuse. STUDY DESIGN: We
      conducted telephone interviews with a random sample of ethnically diverse abused
      women. POPULATION: We included a total of 375 African American, Latina, and non
      Latina white women aged 18 to 46 years with histories of intimate partner abuse
      who attended 1 of 3 primary care clinics in San Francisco, California, in 1997.
      OUTCOMES MEASURED: We measured the relevance and determinants of past
      communication with clinicians about abuse and barriers to communication. RESULTS:
      Forty-two percent (159) of the patients reported having communicated with a
      clinician about abuse. Significant independent predictors of communication were
      direct clinician questioning about abuse (odds ratio [OR]=4.6; 95% confidence
      interval [CI] 3.2-6.6), and African American ethnicity (OR=1.8; 95% CI, 1.1-2.9).
      Factors associated with lack of communication about abuse included immigrant
      status (OR=0.6; 95% CI, 0.3-1.0) and patient concerns about confidentiality
      (OR=0.7; 95% CI, 0.5-0.9). Barriers significantly associated with lack of
      communication were patients' perceptions that clinicians did not ask directly
      about abuse, beliefs that clinicians lack time and interest in discussing abuse,
      fears about involving police and courts, and concerns about confidentiality.
      CONCLUSIONS: Clinician inquiry appears to be one of the strongest determinants of
      communication with patients about partner abuse. Other factors that need to be
      addressed include patient perceptions regarding clinicians' time and interest in
      discussing abuse, fear of police or court involvement, and patient concerns about
      confidentiality.

PMID- 11309219
TI  - Effective management of ice pick pains, SUNCT, and episodic and chronic
      paroxysmal hemicrania.
AB  - Idiopathic stabbing headaches, the SUNCT syndrome, and the paroxysmal hemicranias
      are a group of primary headache disorders that are characterized by brief, short
      lived attacks of head pain, which recur multiple times throughout the day. These
      syndromes are much less prevalent than other types of primary headaches such as
      migraine and tension-type headaches but are significantly more disabling.
      Recognition of these uncommon disorders is important because their management
      differs from standard headache therapies.

PMID- 11309221
TI  - Hereditary non-polyposis colorectal cancer (HNPCC): new germline mutation (190
      191 del AA) in the human MLH1 gene and review of clinical guidelines for
      surveillance of affected families.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common
      genetic diseases comprising at least 5-6% of all colorectal cancers. It is
      characterized by early onset and mostly right-sided tumors (proximal to the
      splenic flexure). Molecular analyses are useful methods for diagnosis in index
      patients and for the detection of risk persons in affected families. A 37-year
      old female patient whose family history fulfilled the criteria for hereditary non
      polyposis colorectal cancer (HNPCC) was studied using PCR and DNA sequencing for
      the detection of mutations in the mismatch repair genes hMSH2 and hMLH1.
      Additionally, literature was reviewed (MEDLINE research until 2000) concerning
      clinical guidelines for surveillance in HNPCC families. A new deletion of two
      adenosine nucleotides (190-191 del AA) at codon 64 in exon 2 of the hMLH1 gene
      was found. The frameshift led to a stop codon at amino acid position 75. This
      mutation is considered to be disease causing in the development of the colorectal
      cancer of this family. Six publications with detailed recommendations for the
      surveillance of risk persons were found in the literature. Following their
      guidelines, colonoscopy is recommended from 20-30 years on for members of a
      family who fulfills either the Amsterdam criteria or the Bethesda criteria in
      combination with a detection of microsatellite instability. Female risk persons
      should be investigated gynecologically, including a transvaginal ultrasound
      examination, from 25-35 years on for the early detection of endometrial or
      ovarian cancer. Recommendations for gastroscopy, abdominal ultrasound examination
      and urine analysis are not given in all publications. Genetic counseling is
      recommended from 18 years on for all members of affected families.

PMID- 11309222
TI  - Cotton-wool spots associated with pancreatic carcinoma.
AB  - BACKGROUND: Malignant tumors of different organs may cause changes in the eye.
      PATIENTS: A 62-year-old woman and a 47-year-old man who both had a metastasizing
      carcinoma of the pancreas suffered from visual disturbances. RESULTS: The 62-year
      old woman experienced cloudy vision in her left eye. The 47-year-old man noticed
      a left visual deterioration. Both patients exhibited cotton-wool spots in both
      eyes. In addition, the man revealed a metastasis of the choroid in the right eye.
      The woman was treated with Gemcitabine (1999), and the man with 5 Fluo
      Uracil/Leukovorin (1997). The cotton-wool spots were reduced in size in the woman
      after treatment with Gemcitabine. The patients had no diabetes mellitus and no
      arterial hypertension. After termination of treatment, their general condition
      deteriorated and they died within a few weeks. CONCLUSION: Cotton-wool spots are
      unusual findings in the retina of a metastasizing carcinoma, suggesting the
      presence of a retinal ischemia. Therefore, early screening of patients with
      metastasizing pancreas carcinoma for retinal abnormalities may be important.

PMID- 11309223
TI  - Sandwich ELISA for proANP 1-98 facilitates investigation of left ventricular
      dysfunction.
AB  - Proatrial natriuretic peptides are proposed to be sensitive and specific markers
      for various stages of heart deficiency. Here we present a rapid and specific
      sandwich immunoassay for the measurement of proANP 1-98 in biological fluids like
      plasma, serum urine. No sample preparation prior to the assay is necessary.
      Polyclonal antibodies specific for distinct epitopes of proANP 1-98, predicted to
      be highly immunogenic, were raised in sheep and purified by immunoaffinity
      chromatography prior to use in the assay. Antigen binding sites of the antibodies
      were determined by epitope mapping with a set of peptide fragments. The capture
      antibody, specific for proANP 16-23, is coated directly onto microtiter plates.
      Recombinant proANP 1-98 is used as a standard. The biotinylated detection
      antibody, specific for proANP 80-88, is incubated simultaneously with 20microl of
      sample for 150 min. Signal is generated with a streptavidin-HRPO-conjugate and
      TMB as substrate. The detection limit of the assay is 50 pmol/l; intraassay CVs
      are below 5%, interassay CVs are lower than 10%. Dilution curves show good
      linearity, recovery of synthetic peptide ranged between 85% and 91%. Reference
      values from healthy volunteers range from 0 to 2000 pmol/l in human plasma. We
      conclude this assay is a easy to handle, quick and reliable method for routine
      measurement of proANP 1-98 and the presented manuscript describes the procedure
      and performance of this ELISA in detail.

PMID- 11309224
TI  - Severe bleeding complications in HIV-positive haemophiliac patients treated with
      protease inhibitors.
AB  - The availability of more potent drugs for the treatment of human immunodeficiency
      virus (HIV) infection has led to the development of aggressive drug regimens,
      including the widespread use of HIV protease inhibitors. Several reports have
      indicated increased bleeding complications in haemophiliac patients after
      starting treatment with protease inhibitors. We present two cases of
      exceptionally severe hemorrhagic events in HIV-positive patients with haemophilia
      A after starting HIV protease inhibitors, resulting in significant morbidity and
      mortality. One patient developed a progressive paranephric pseudotumor becoming
      symptomatic only one month after the start of ritonavir. The second patient
      presented with an intracranial bleed, resulting in his death within forty-eight
      hours, nineteen weeks after he was started on nelfinavir. Both patients showed an
      excellent antiviral response to the HIV-protease inhibitors with significant
      decrease in their HIV-RNA titers. Potentially serious hemorrhagic complications
      that require emergent intervention may occur in HIV-positive haemophiliac
      patients undergoing therapy with protease inhibitors. Clinicians should be alert
      to these complications.

PMID- 11309225
TI  - 2nd European symposium on liquid ventilation.
AB  - After the successful meeting in Berlin, advances and research results in the
      understanding of liquid ventilation has been performed. About 80 applied and
      basic scientists met in the 1st European Symposium, from clinicians
      (pediatricians, neonatologists, intensivists, etc.) to other basic scientists
      (physiologists, biologists, bioengineerings, etc.). Furthermore, we also invited
      representatives of pharmaceutic industry interested in this hot topic. Our main
      goal is to provide an opportunity for all liquid researchers in this field to
      meet together and with the top scientists of Liquid Ventilation Research. We
      planned to provide both a scientific and a friendly atmosphere to enhance the
      exchange of experiences and to facilitate future plans. We hope this 2nd European
      Symposium will be a continuation point for collaboration of groups in Europe, to
      study all research aspects of the technique to carry on future trials. There are
      still a lot of unanswered questions to be solved. Among the unsolved issues and
      practical questions we would like to point out the following items: 1.
      Perfluorocarbon: which product to use and how to deliver it. 2. Perfluorocarbon
      interactions in the lung. 3. Perfluorocarbon. Toxicity and cytoprotection. 4.
      Partial Liquid Ventilation: ventilatory strategies from delivering to weaning. 5.
      Impact of Partial Liquid Ventilation Experimental and clinical aspects. 6.
      General discussion and plan for the future. We know that none of these questions
      can be completely answered now, but hope collaboration and communication will
      bring us closer to achieve these goals. Moreover, concerted actions should be
      started to search for research grant founding. For all those reasons we would
      like to thank all active and passive participants, who came to Bilbao to present,
      discuss and foster future work in Liquid Ventilation.

PMID- 11309226
TI  - Amoxicillin-clavulanic acid therapy may be associated with severe side effects --
      review of the literature.
AB  - INTRODUCTION: There is a growing body of evidence that amoxicillin-clavulanic
      acid may induce severe adverse effects in patients. METHODS: A medline search of
      case reports and reviews on amoxicillin-clavulanic acid induced adverse effects
      was performed. The criteria of a consensus conference on the reporting of drug
      induced liver disease were applied. RESULTS: Amoxicillin-clavulanic acid has been
      associated with drug-induced cholestatic hepatitis in 208 reported patients. In
      153 evaluable patients there were 106 males and 47 females with a mean age of 60
      years (1-90). Liver associated co-morbidity and co-medication does not play a
      major part in the development of disease. In most instances respiratory tract
      infection and sinusitis were treated by amoxicillin-clavulanic acid with a mean
      treatment duration of 13.9 days and a reaction time until first onset of jaundice
      of 25.2 days average. Infection and cholestasis from other reason were ruled out
      in most patients. Liver injury was classified according to laboratory parameters
      to be hepatocellular in 35 patients, cholestatic in 24 patients and mixed in 83
      patients. Normalization of liver enzymes was observed 11.5 weeks after onset of
      drug administration (average); three of 153 patients did not survive the adverse
      event. CONCLUSION: Amoxicillin-clavulanic acid which is marketed for treatment of
      respiratory infections and sinusitis/otitis may in some cases induce severe
      adverse effects and death in patients of different age, especially if they are on
      multidrug regimens. In consideration of this fact many authors recommend to
      reflect carefully, whether amoxicillin-clavulanic acid is necessary in treatment
      of patients with localized or uncomplicated infections. If amoxicillin-clavulanic
      acid is prescribed, transaminase, alkaline phosphatase and bilirubin tests should
      be obtained within the first two weeks and after four to five weeks after
      beginning of treatment to recognize early enough undesired hepatic side effects.

PMID- 11309227
TI  - Current aspects of colchicine therapy -- classical indications and new
      therapeutic uses.
AB  - Colchicine has been traditionally used for the treatment of gout. At present
      there is no generally accepted alternative to colchicine for the treatment of
      acute attacks or for the prevention of further attacks. The complex actions of
      this substance, which are mainly attributable to its stabilising action on the
      cytoskeleton and cell membranes, and its special pattern of distribution form the
      basis for the results presented here regarding the prophylactic or therapeutic
      actions of colchicine in a whole range of other diseases. This is all the more
      significant in that in several instances it concerns diseases that have so far
      been unsatisfactorily controlled by other treatments. Because of its astonishing
      absence of side effects, some authors consider that low dose colchicine may be
      considered as an alternative to previous therapies or even a means of first
      choice. It is therefore incorrect to think that medical research has shown little
      interest in this long-known potential and has not sought to confirm promising
      options by means of controlled studies. Fibrotic and inflammatory systemic
      diseases and those in which leucocytic chemotaxis play a role seem to be
      particularly predestined for this.

PMID- 11309228
TI  - Paradigm change in 30 years peritonitis treatment -- a review on source control.
AB  - Peritonitis remains a hot spot for surgeons despite advancements in surgical
      technique and intensive care treatment. There is an ongoing interest to improve
      the survival rate by analyzing the pathogenesis and pathophysiology of this
      threatening disease. - The significance of source control, e.g., eradication of a
      focus of infection, elimination of microbial contamination and restoration of
      local environment, is well recognized since the beginning of the last century.
      Recently the term "source control" has gained new interest with regard to
      guidelines for clinical studies. It appears that despite stratification in most
      clinical peritonitis studies there is still a lack of comparability of those
      studies with regard to source control. A medline search on peritonitis and source
      control was performed and 90 studies were evaluated for information on source
      control evaluation. In summary, there is no uniform definition of source control
      available. Most studies in peritonitis treatment are according to evidence based
      medicine level 3-5 evidence. Lack of hard scientific evidence how to measure the
      success of source control had to be substituted by surgical experience. Re
      operation or relaparotomy may be considered as acknowledgment that source control
      failed. Controversy exists about primary anastomosis in the inflammed peritoneum.
      Despite all efforts and more patients enrolled in studies to improve surgical
      treatment of peritonitis in thirty years it is obvious that the mortality rate
      has decreased only marginally from 40% to 30%. Commonly accepted principles for
      source control documentation and evaluation should be established and confirmed
      in multi-center studies before further studies with new compounds are started.

PMID- 11309229
TI  - Role of gamma delta T-lymphocytes in HIV infection.
AB  - T-lymphocytes expressing the gamma delta T-cell receptor (TCR) comprise a small
      proportion (1-5%) of circulating CD3(+) T-lymphocytes. While T-cells expressing a
      V delta 2V gamma 9-encoded TCR dominate among peripheral blood gamma delta T
      lymphocytes in healthy individuals, significant alterations in the gamma delta
      TCR repertoire are observed in HIV-infected persons. These changes are due to the
      selective preservation (and frequently moderate expansion) of V delta 1
      expressing cells and the simultaneous depletion of V delta 2-expressing cells. In
      this brief review, we discuss the alterations in the gamma delta T-lymphocyte
      compartment in HIV infection, with special emphasis on the potential role of
      gamma delta T-cell in the immune defense against HIV.

PMID- 11309230
TI  - Heparin protects local skin microcirculation in 210 minutes-long intravital
      microscopy observations under general anaesthesia.
AB  - Prolonged immobilization of severely ill, bed-ridden patients results in
      formation of pressure ulcers following inappropriate tissue blood perfusion, and
      local activation of leukocyte - endothelial cell interactions (L/EC). Various
      treatment modalities were implemented to improve local microcirculation with
      controversial results. The aim of our study was to investigate the influence of
      heparin and buflomedil, drugs improving the microcirculation, on local skin blood
      perfusion using intravital fluorescent microscopy (IVM) technique. MATERIAL AND
      METHODS: Experiments were carried out on 24 male hairless mice under inhalatory
      isofluran anaesthesia. Intravenous injection of FITC-dextran (150 kD, 5%) allowed
      to visualize capillaries during IVM, after immobilisation of hind limb, in an
      observation chamber. Observations were performed after i.v. injection of heparin
      (66 IU/kg b.w., n = 8) or buflomedil (6 mg/kg b.w., n = 8) 30, 120 and 210
      minutes after chamber installation. Observations were recorded in 30 sec
      sequences on S-VHS tapes and evaluated using special software. Functional
      capillary density (FCD), defined as a total length of red cells perfused
      capillaries per observation field (expressed in cm/cm(2)), postcapillary venule
      diameters, and number of sticking leukocytes per 0.2 mm vessel length during 30
      sec observation time, served as parameters of skin blood perfusion and activation
      of L/EC interactions. RESULTS: A statistically significant decrease of FCD from
      152.7 +/- 38.5 to 100.7 +/- 36.7 cm/cm (2) (p<0.05) was observed in control
      animals during 210 min lasting observation. Administration of heparin prevented
      decrease in FCD occurring in control animals during intravital microscopy,
      whereas buflomedil was found ineffective. Both drugs induced a nonsignificant
      reduction in the number of sticking leukocytes, whereas no changes in
      postcapillary venule diameters could be observed. CONCLUSION: The results suggest
      a protective effect of heparin in clinical therapeutic doses against impairment
      of skin perfusion during IVM. This observation may justify a trial on the effects
      of heparin in prevention of development of pressure ulcers.

PMID- 11309231
TI  - Levels of insulin-like growth factor after stem cell transplantation.
AB  - Some cytokines, i.e. tumor necrosis factor-, interleukin-6 and soluble
      interleukin-2 receptors are associated with complications of stem cell
      transplantation. Insulin-like growth factors (IGFs) are a family of peptides
      essential for the proliferation of normal and malignant cells. Recently increased
      levels of IGFs have been associated with the development of malignant tumors. In
      this communication we report on 96 measurements of insulin-like growth factor-I
      (IGF-1), insulin-like growth factor-II (IGF-2), and insulin-like growth factor
      binding protein-3 (IGFBP-3) performed in 19 patients following stem cell
      transplants. Seventeen patients had allogeneic and 2 patients autologous
      transplants. Most IGF determinations were made at days 0, 7, 14, 21 and 28, some
      at other time points. The baseline values (day 0) of IGF-1 and IGFBP-3 were not
      different from controls. IGF-2 values were slightly lower than controls.
      Following transplantation, a consistent increase of IGF-1 was observed in 9/16
      patients at days 7 and 14. Later the values decreased again. IGF-2 and IGFBP-3
      did not change significantly after transplantation. No direct correlation could
      be established with the severity of graft-versus-host disease, levels of
      interleukin-6 and the time to hematopoietic recovery. A potential relevance of
      IGFs following stem cell transplantation may be the early diagnosis of liver
      damage and the development of second malignancies. More studies are necessary to
      investigate the pathophysiology and the clinical relevance of the increase of IGF
      1 following stem cell transplantation.

PMID- 11309232
TI  - Depressor and regionally-selective vasodilator effects of human and rat urotensin
      II in conscious rats.
AB  - The regional haemodynamic effects of rat or human urotensin II (U-II) 3, 30, 300
      and 3000 pmol kg(-1), i.v.) were assessed in separate groups of conscious,
      unrestrained, male, Sprague-Dawley rats (n=8 in each). Rat and human U-II had
      similar effects. At a dose of 3 pmol kg(-1), neither peptide had any significant
      action, while at a dose of 30 pmol kg(-1), there was a transient mesenteric
      vasodilatation (significant only for rat U-II). At doses of 300 and 3000 pmol kg(
      1), there were dose-dependent tachycardias, and mesenteric and hindquarters
      hyperaemic vasodilatations. Thus, in conscious rats, the predominant
      cardiovascular action of rat and human U-II is vasodilatation. This is in
      contrast to recent findings with human U-II in non-human primates, but is
      consistent with effects on human isolated resistance vessels.

PMID- 11309233
TI  - Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap
      survival.
AB  - We have examined the role of nitric oxide (NO) in a model of functional
      angiogenesis in which survival of a skin flap depends entirely on angiogenesis to
      provide an arterial blood supply to maintain tissue viability. The different
      effects of nitric oxide synthase (NOS) inhibitors on rat skin flap survival
      appeared to be explained on the basis of their NOS isoform selectivity. Skin flap
      survival was decreased by iNOS-selective (inducible NOS) inhibitors, S-methyl
      isothiourea, aminoguanidine and aminoethylthiorea; unaffected by the non
      selective inhibitor nitro-imino-L-ornithine; and enhanced by the cNOS
      (constitutive NOS, that is endothelial NOS (eNOS) and neuronal NOS (nNOS))
      inhibitor, nitro-L-arginine methyl ester. Skin flap survival was reduced in mice
      with targeted disruption of the iNOS gene (iNOS knockout mice), and the
      administration of nitro-L-arginine methyl ester significantly increased flap
      survival in iNOS knockout mice (P<0.05). iNOS immunoreactivity was identified in
      mast cells in the angiogenic region. Immunoreactive vascular endothelial growth
      factor (VEGF) and basic fibroblast growth factor were also localized to mast
      cells. The combination of interferon-gamma and tumour necrosis factor-alpha
      induced NO production and increased VEGF levels in mast cells cultured from bone
      marrow of wild-type, but not iNOS KO mice. The increased tissue survival
      associated with the capacity for iNOS expression may be related to iNOS-dependent
      enhancement of VEGF levels and an ensuing angiogenic response. Our results
      provide both pharmacological and genetic evidence that iNOS activity promotes
      survival of ischaemic tissue.

PMID- 11309234
TI  - The effects of the statins lovastatin and cerivastatin on signalling by the
      prostanoid IP-receptor.
AB  - The prostanoid-IP receptor may be unique among G protein coupled receptors in
      that it is isoprenylated. In this study, we investigated the effects of the
      statins lovastatin and cerivastatin on signalling by the mouse (m) IP and the
      human (h) IP receptors, over-expressed in human embryonic kidney (HEK) 293 cells
      and by the hIP receptor, endogenously expressed in human erythroleukaemia cells.
      Both statins significantly reduced IP receptor-mediated cyclic AMP generation and
      intracellular calcium ([Ca(2+)](i)) mobilization in a time and concentration
      dependent manner but had no effect on signalling by the non-isoprenylated beta(2)
      adrenergic receptor or by the human prostanoid-TP receptor isoforms. Cerivastatin
      (IC(50), 50 - 90 nM) was significantly more potent than lovastatin (IC(50), 0.80 
      4.2 microM) in inhibiting IP receptor signalling. Whereas IC(50) values
      indicated that the hIP receptor was significantly more sensitive than the mIP
      receptor to the statins, the extent of inhibition of cyclic AMP generation by the
      mIP receptor was significantly greater than that of the hIP receptor to either
      statin, even at the highest concentrations used. Pretreatment with either statin
      significantly reduced IP receptor mediated desensitization of signalling by the
      h.TPalpha, but not by the h.TPbeta, receptor isoform. These data generated in
      whole cells point to the possibility that statin therapy may interfere with IP
      receptor signalling in vivo; such interference may be extenuated under conditions
      where circulating statin levels are elevated and may account, in part, for some
      of the pleiotropic affects of the statins not attributed solely to their lipid
      lowering properties.

PMID- 11309235
TI  - Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine
      treated rats, and loss of neuroprotection in alpha4 nicotinic receptor subunit
      knockout mice.
AB  - The present study examined the effect of a range of doses of chronic nicotine
      (0.75, 1.5, 3.0 and 30.0 mg kg(-1) day(-1), s.c., 14 days) upon striatal
      dopaminergic nerve terminal survival following 6-hydroxydopamine (6-OHDA; 10
      microg intrastriatal unilaterally) in rats; and the effects of acute nicotine (1
      mg kg(-1), s.c.) pretreatment upon striatal neurodegeneration induced by
      methamphetamine (5 mg kg(-1), i.p., three doses at 2 h intervals) in wild-type
      and alpha4 nicotinic receptor (nAChR) subunit knockout mice. In both models of
      Parkinsonian-like damage, loss of striatal dopaminergic nerve terminals was
      assessed by [(3)H]-mazindol autoradiography. In rats, chronic nicotine infusion
      delivered by osmotic minipump implanted subcutaneously 7 days prior to
      intrastriatal 6-OHDA injection produced significant and dose-related protection
      against 6-OHDA-induced neurodegeneration. Low (0.75 and 1.5 mg kg(-1) day(-1))
      but not high (3.0 and 30.0 mg kg(-1) day(-1)) nicotine doses significantly
      inhibited 6-OHDA-induced degeneration. In wild-type mice, acute nicotine
      treatment produced significant inhibition of methamphetamine-induced
      neurodegeneration. In alpha4 nAChR subunit knockout mice, acute nicotine
      treatment failed to inhibit methamphetamine-induced neurodegeneration. Nicotine
      is capable of protecting dopaminergic neurons against Parkinsonian-like
      neurodegeneration in vivo. In rats, this neuroprotective effect is critically
      dependent upon nicotine dose and is consistent with the activation of nAChRs, as
      high, desensitizing doses of nicotine fail to be neuroprotective. Further,
      neuroprotection is absent in alpha4 nAChR subunit knockout mice. The current
      results therefore suggest that activation of alpha4 subunit containing nAChRs
      constitutes a major component of the neuroprotective effect of nicotine upon
      Parkinsonian-like damage in vivo.

PMID- 11309236
TI  - Thrombin-induced p38 mitogen-activated protein kinase activation is mediated by
      epidermal growth factor receptor transactivation pathway.
AB  - Thrombin is a potent mitogen for vascular smooth muscle cells (VSMC) and has been
      implicated its pathogenic role in vascular remodelling. However, the signalling
      pathways by which thrombin mediates its mitogenic response are not fully
      understood. We have previously reported that thrombin activates p38 mitogen
      activated protein kinase (p38 MAPK) by a tyrosine kinase-dependent mechanism, and
      that p38 MAPK has a role in thrombin-induced mitogenic response in rat VSMC. In
      the present study, we examine the involvement of epidermal growth factor (EGF)
      receptor in thrombin-induced p38 MAPK activation. We found that thrombin induced
      EGF receptor tyrosine phosphorylation (transactivation) in A10 cells, a clonal
      VSMC cell line. A selective inhibitor of EGF receptor kinase (AG1478) inhibited
      the p38 MAPK activation in a dose-dependent manner, whereas it had no effect on
      the response to platelet-derived growth factor (PDGF). EGF receptor
      phosphorylation induced by thrombin was inhibited by BAPTA-AM and GF109203X,
      which suggest a requirement for intracellular Ca(2+) increase and protein kinase
      C. We next examined the effect of AG1478 on thrombin-induced DNA synthesis.
      AG1478 inhibited thrombin-induced DNA synthesis in a dose-dependent manner. In
      contrast, PDGF-induced DNA synthesis was not affected by AG1478. In conclusion,
      these data suggest that the EGF receptor transactivation and subsequent p38 MAPK
      activation is required for thrombin-induced proliferation of VSMC.

PMID- 11309237
TI  - Novel histamine H(3)-receptor antagonists and partial agonists with a non
      aminergic structure.
AB  - We determined the affinities of eight novel histamine H(3)-receptor ligands
      (ethers and carbamates) for H(3)-receptor binding sites and their
      agonistic/antagonistic effects in two functional H(3)-receptor models. The
      compounds differ from histamine in that the ethylamine chain is replaced by a
      propyloxy chain; in the three ethers mentioned below (FUB 335, 373 and 407), R is
      n-pentyl, 3-methylbutyl and 3,3-dimethylbutyl, respectively. The compounds
      monophasically inhibited [(3)H]-N(alpha)-methylhistamine binding to mouse
      cerebral cortex membranes (pK(i) 7.51 - 9.53). The concentration-response curve
      of histamine for its inhibitory effect on the electrically evoked [(3)H]
      noradrenaline overflow from mouse cortex slices was shifted to the right by these
      compounds (apparent pA(2) 6.61 - 8.00). Only FUB 373 and 407 inhibited the evoked
      overflow by themselves (intrinsic activities 0.3 and 0.4); these effects were
      counteracted by the H(3)-receptor antagonist clobenpropit. [(35)S]-GTPgammaS
      binding to mouse cortex membranes was stimulated by the H(3)-receptor agonist (R)
      alpha-methylhistamine in a manner sensitive to clobenpropit. Among the novel
      compounds only FUB 373 and 407 stimulated [(35)S]-GTPgammaS binding (intrinsic
      activities 0.6 and 0.4). In conclusion, the novel compounds are partial H(3)
      receptor agonists (FUB 373 and 407) or H(3)-receptor antagonists; comparison with
      FUB 335 shows that the transition from antagonist to agonist is caused by a
      slight structural change. A protonated N atom in the side chain is not necessary
      for agonism at H(3) receptors, proposing a receptor-ligand interaction different
      from that of classical agonists.

PMID- 11309238
TI  - Role of the haeme oxygenase/carbon monoxide pathway in mechanical nociceptor
      hypersensitivity.
AB  - The cleavage of haeme by haeme oxygenase (HO) yields carbon monoxide (CO), a
      biologically active molecule which exerts most of its effects via activation of
      soluble guanylate cyclase (sGC). In the present study, we tested the hypothesis
      that endogenous CO could modulate inflammatory hyperalgesia. The intensity of
      hyperalgesia was investigated in a model of mechanical nociceptor
      hypersensitivity in rats. The intra-plantar (i.pl.) administration of the HO
      inhibitor, ZnDPBG (Zinc deuteroporphyrin 2,4-bis glycol), potentiated in a dose
      dependent manner the mechanical nociceptor hypersensitivity evoked by i.pl.
      administration of carrageenan. The mechanical hypersensitivity evoked by i.pl.
      injection of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF
      alpha), but not interleukin-8 (IL-8), prostaglandin E(2) (PGE(2)) or dopamine,
      was also enhanced by ZNDPBG: Moreover, the haeme (HO substrate) injection in the
      paws reduced the hypersensitivity evoked by IL-1beta, but not PGE(2).
      Furthermore, i.pl. administration of the gas CO reduced the hypersensitivity
      elicited by PGE(2). The inhibitory effect of haeme and CO upon mechanical
      nociceptor hypersensitivity were counteracted by a soluble guanylate cyclase
      (sGC) inhibitor, ODQ (1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one), suggesting
      that this effect of CO is mediated via cyclic GMP. Finally, the inhibitory effect
      of CO upon mechanical nociceptor hypersensitivity was prevented by the NO
      synthase blocker, L-NMMA (N(G)-monomethyl L-arginine), suggesting that the
      impairment of mechanical hypersensitivity elicited by CO depends on the integrity
      of the NO pathway. In conclusion, the results presented in this paper imply that
      endogenously CO produced by HO plays an anti-hyperalgesic role in inflamed paws,
      probably by increasing the intracellular levels of cyclic GMP in the primary
      afferent neurone.

PMID- 11309239
TI  - In vivo steady-state pharmacokinetic outcome following clinical and toxic doses
      of racemic citalopram to rats.
AB  - The thymoleptic drug citalopram (CIT) belongs to the selective serotonin reuptake
      inhibitors (SSRIs) and is today extensively used in psychiatry. Further
      clarification of the enantiomer-selective distribution of racemic CIT in both
      clinical and toxic doses is highly warranted. By a steady-state in vivo paradigm,
      rats underwent chronic systemic exposure for 10 days by using osmotic pumps and
      the total as well as the individual distributions of the S- and R-enantiomers of
      CIT, and its metabolites in serum and two different brain regions, were analysed.
      In serum, the S/R ratios in the groups treated with 10, 20, or 100 mg kg(-1) day(
      1) were 0.94, 0.83, and 0.34, respectively. The ratios were almost the same in
      the brain regions. In the group treated with 100 mg kg(-1) day(-1), the serum and
      brain total CIT levels were found to be 20 times and 6 - 8 times higher than in
      the rats treated with 10 or 20 mg kg(-1) day(-1), respectively. In all groups,
      the CIT levels were higher in brain tissue as compared to serum. In a spontaneous
      open-field behavioural test, a correlation between clinical and toxic drug
      concentrations was observed. In conclusion, the R-enantiomer was present in an
      increased proportion compared with the S-enantiomer when higher steady-state CIT
      concentration was prevailing. This is of particular interest, since the S
      enantiomer is responsible for the inhibition of serotonin reuptake in vitro. The
      present data may be of importance, as full understanding on where different
      racemic or enantiomeric drug effects of CIT and its main metabolites are
      unravelled.

PMID- 11309240
TI  - Incorporation of sodium channel blocking and free radical scavenging activities
      into a single drug, AM-36, results in profound inhibition of neuronal apoptosis.
AB  - AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na(+)
      channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis
      due to Na(+) channel activation, together with increased reactive oxygen species
      (ROS) production, are thought to contribute to neuronal death. Since neuronal
      death in the penumbra of the ischaemic lesion is suggested to occur by apoptosis,
      we investigated the ability of AM-36, antioxidants and Na(+) channel antagonists
      to inhibit toxicity induced by the neurotoxin, veratridine in cultured cerebellar
      granule cells (CGC's). Veratridine (10 - 300 microM) concentration-dependently
      reduced cell viability of cultured CGC's. Under the experimental conditions
      employed, cell death induced by veratridine (100 microM) possessed the
      characteristics of apoptosis as assessed by morphology, TUNEL staining and DNA
      laddering on agarose gels. Neurotoxicity and apoptosis induced by veratridine
      (100 microM) were inhibited to a maximum of 50% by the antioxidants, U74500A (0.1
      - 10 microM) and U83836E (0.03 - 10 microM), and to a maximum of 30% by the Na(+)
      channel blocker, dibucaine (0.1 - 100 microM). In contrast, AM-36 (0.01 - 10
      microM) completely inhibited veratridine-induced toxicity ( IC(50) 1.7 (1.5 -
      1.9) microM, 95% confidence intervals (CI) in parentheses) and concentration
      dependently inhibited apoptosis. These findings suggest veratridine-induced
      toxicity and apoptosis are partially mediated by generation of ROS. AM-36, which
      combines both Na(+) channel blocking and antioxidant activity, provided superior
      neuroprotection compared with agents possessing only one of these actions. This
      bifunctional profile of activity may underlie the potent neuroprotective effects
      of AM-36 recently found in a stroke model in conscious rats.

PMID- 11309241
TI  - Characterization of the effects of isoprostanes on platelet aggregation in human
      whole blood.
AB  - We tested the effects of 11 commercially-available isoprostanes on platelet
      aggregation directly or when triggered by the thromboxane receptor agonist U46619
      or collagen in healthy human citrated blood using a whole blood aggregometer.
      None of the isoprostanes tested triggered aggregation alone, nor facilitated
      aggregation by a sub-threshold dose of U46619 or collagen. Five isoprostanes
      inhibited aggregation (rank order of potency 8-iso PGE(1)>8-iso PGE(2)>8-iso
      PGF(2alpha)>8-iso PGF(3alpha)>8-iso-13,14-dihydro-15-keto PGF(2alpha)). Blood
      incubated with LPS to induce a gross inflammatory response exhibited a time
      dependent (2 - 12 h) reduction in aggregation to U46619 but maintained a
      consistent response to collagen. Under these conditions, as in control blood,
      none of the isoprostanes tested induced aggregation. In fact, the inhibitory
      actions of isoprostanes on U46619-induced aggregation were enhanced in blood
      treated with LPS. L-NAME inhibited aggregation induced by U46619 in fresh blood
      and in blood treated with LPS. In the presence of L-NAME, (with or without LPS)
      none of the isoprostanes tested induced aggregation but retained their inhibitory
      action. Thus, in human whole blood the action of 8-iso PGE(1), 8-iso PGE(2), 8
      iso PGF(2alpha), 8-iso PGF(3alpha), and 8-iso-13,14-dihydro-15-keto PGF(2alpha)
      is antiaggregatory. Moreover, this inhibitory capacity is still apparent and may
      be enhanced in blood subjected to inflammatory stimulation.

PMID- 11309242
TI  - The nitric oxide donor pentaerythritol tetranitrate can preserve endothelial
      function in established atherosclerosis.
AB  - Recent results suggested that long-term treatment with a low dose of the organic
      nitrate pentaerythritol tetranitrate (PETN, 6 mg kg(-1) per day) for 16 weeks
      slightly decreases aortic superoxide production in normal rabbits. We sought to
      determine if PETN can preserve endothelium dependent relaxation (EDR) in
      atherosclerotic rabbits. Three groups of 9 - 10 New Zealand White rabbits
      received a cholesterol chow (0.75%) for 16 weeks. One group (CHOL16) served as
      control and two groups were fed for another 16 weeks a cholesterol-chow without
      (CHOL32) or with 6 mg PETN kg(-1) per day (PETN32). Isolated aortic rings of
      CHOL16 showed a typical impairment of EDR with a maximal relaxation at 1 microM
      acetylcholine of 28+/-16%. In CHOL32-rings EDR was completely impaired. In
      striking contrast, EDR in PETN32 (24+/-15%) was similar to that of CHOL16
      indicating a protective effect of PETN on endothelial function. Vascular
      superoxide production measured with the lucigenin method was not different
      between the groups. Aortic lesion formation in PETN32 was smaller than in CHOL32
      (P<0.008). The onset of copper-induced LDL-oxidation (lag-time) after 16 weeks of
      cholesterol feeding (214+/-9 min) was reduced in CHOL32 (168+/-24 min, P=0.035)
      but not in PETN32 (220+/-21 min). This indicates prevention of increased LDL
      oxidation by PETN. The halfmaximal effective vasodilator concentrations of PETN
      (in -logM) were identical in CHOL16 (7.9+/-0.1), CHOL32 (7.6+/-0.2) and PETN32
      (7.7+/-0.2). Similar results were obtained with S-nitroso-N-acetyl-D,L
      penicillamine. These data suggest that PETN can reduce the progression of lesion
      formation, endothelial dysfunction and of LDL-oxidation in established
      atherosclerosis.

PMID- 11309243
TI  - Role of p38 MAP kinase in LPS-induced airway inflammation in the rat.
AB  - We investigated the effect of the p38 kinase inhibitor SB 203580 on airway
      inflammation induced by aerosolized lipopolysaccharide (LPS) in male Wistar rats.
      SB 203580 significantly inhibited (ED(50)=15.8 mg kg(-1)) plasma levels of TNF
      alpha in rats challenged with LPS (1.5 mg kg(-1), i.p.). Aerosolized LPS induced
      a peak in TNF-alpha levels and the initiation of a neutrophilic response in
      bronchoalveolar lavage (BAL) fluid at the 2 h time point. Furthermore, the 4 h
      time point was associated with the peak in IL-1beta levels and the initial
      plateau of neutrophilia observed in the BAL fluid. SB 203580 (100 mg kg(-1)), had
      no effect on peak TNF-alpha levels or the associated neutrophilia in the BAL.
      Interestingly, the PDE 4 inhibitor RP 73401 (100 mg kg(-1)) significantly reduced
      both TNF-alpha levels and neutrophilic inflammation. However, the BAL fluid from
      rats pre-treated with either compound significantly inhibited TNF-alpha release
      from cultured human monocytes 18 h after LPS treatment (83.6 and 44.5%
      inhibition, respectively). Alternatively, SB 203580 (100 mg kg(-1)) produced dose
      related inhibition of BAL IL-1beta levels (67.5% inhibition, P<0.01) and BAL
      neutrophilia (45.9% inhibition, P<0.01) 4 h after LPS challenge. P38 protein was
      present in lung tissue and the level of expression was not affected by LPS
      treatment. P38 kinase appears to be involved in the release of IL-1beta and the
      sustained neutrophilic response in the BAL fluid. This data may suggest a role
      for p38 inhibitors in the treatment of airway inflammatory diseases in which
      neutrophilia is a feature of the lung pathology.

PMID- 11309244
TI  - Effects of authentic and VLDL hydrolysis-derived fatty acids on vascular smooth
      muscle cell growth.
AB  - There are contradictory findings regarding the effects of free fatty acids on
      vascular smooth muscle cell (VSMC) growth. In the present study we investigated
      the effects of fatty acids released from hydrolysis of human VLDL triglycerides
      by lipoprotein lipase and of the fatty acids most abundant in the hydrolysed
      VLDL, namely oleic, linoleic, palmitic and myristic acid, all non albumin-bound,
      on VSMC growth. The effect of fatty acids on VSMC growth was assessed by [(3)H]
      thymidine incorporation, colourimetrically, by cell counting, by determination of
      the cytoplasmic histone-associated DNA fragments and the caspase 3 activity. The
      fatty acid concentrations were determined by gas chromatography-mass
      spectrometry. Stimulation of ERK1/2 and p38 was determined by the
      chemiluminescence Western blotting method. Incubation of VSMC with purified VLDL
      (100 microg ml(-1)) and lipoprotein lipase (35 u ml(-1)) led to almost complete
      cell death although the ERK1/2 and the p38 MAP kinases were stimulated. The
      EC(50) of oleic, linoleic, myristic and palmitic acid were 4.6+/-1.3, 2.4+/-0.2,
      116+/-10 and 287+/-30 microM, respectively. The estimated EC(50) of myristic and
      palmitic acid when derived from hydrolysed VLDL were 10 and 8 times,
      respectively, lower than when used alone. Apoptosis was not involved in the fatty
      acid-induced VSMC growth suppression/death. We conclude that (a) non albumin
      bound fatty acids cause VSMC necrosis in a dose-dependent manner with a parallel
      ERK1/2 and p38 stimulation, (b) unsaturated fatty acids are more toxic to VSMC
      than saturated, and (c) saturated fatty acids are more toxic to VSMC in the
      hydrolysed VLDL than when used individually.

PMID- 11309245
TI  - Signal transduction pathways involved in kinin B(2) receptor-mediated
      vasodilation in the rat isolated perfused kidney.
AB  - The signal transduction pathways involved in kinin B(2) receptor-related
      vasodilation were investigated in rat isolated perfused kidneys. During
      prostaglandin F(2alpha) or KCl-induced constriction, the vasodilator response to
      a selective B(2) receptor agonist, Tyr(Me)(8)bradykinin (Tyr(Me)(8)BK), was
      assessed. Tyr(Me)(8)BK produced a concentration- and endothelium-dependent
      relaxation that was decreased by about 30 - 40% after inhibition of nitric oxide
      (NO) synthase by N(G)-nitro-L-arginine (L-NOARG) or of cyclo-oxygenase by
      indomethacin; a greater decrease (about 40 - 50%) was observed after concomitant
      inhibition of the two pathways. High extracellular K(+) diminished Tyr(Me)(8)BK
      induced relaxation by about 75% suggesting a major contribution of endothelium
      derived hyperpolarization. The residual response was almost completely suppressed
      by NO synthase and cyclo-oxygenase inhibition. The K(+) channel inhibitors,
      tetrabutylammonium (non-specific) and charybdotoxin (specific for Ca(2+)
      activated K(+) channel), suppressed Tyr(Me)(8)BK-induced relaxation resistant to
      L-NOARG and indomethacin. Inhibition of cytochrome P450 (clotrimazole or 7
      ethoxyresorufin) decreased the NO/prostanoids-independent relaxation to
      Tyr(Me)(8)BK by more than 60%, while inhibition of the cannabinoid CB(1) receptor
      (SR 141716A) had only a moderate effect. Acetylcholine induced a concentration
      dependent relaxation with characteristics nearly similar to the response to
      Tyr(Me)(8)BK. In contrast, the relaxation elicited by sodium nitroprusside was
      potentiated in the absence of NO (L-NOARG or removal of endothelium) but remained
      unchanged otherwise. These results indicate that the activation of kinin B(2)
      receptors in the rat isolated kidney elicits an endothelium-dependent
      vasorelaxation, mainly dependent on the activation of charybdotoxin-sensitive
      Ca(2+)-activated K(+) channels. In addition, cytochrome P450 derivatives appear
      to be involved.

PMID- 11309246
TI  - Characterization of palmitoylethanolamide transport in mouse Neuro-2a
      neuroblastoma and rat RBL-2H3 basophilic leukaemia cells: comparison with
      anandamide.
AB  - The endogenous cannabinoid receptor agonist anandamide (AEA) and the related
      compound palmitoylethanolamide (PEA) are inactivated by transport into cells
      followed by metabolism by fatty acid amide hydrolase (FAAH). The cellular uptake
      of AEA has been characterized in detail, whereas less is known about the
      properties of the PEA uptake, in particular in neuronal cells. In the present
      study, the pharmacological and functional properties of PEA and AEA uptake have
      been investigated in mouse Neuro-2a neuroblastoma and, for comparison, in rat RBL
      2H3 basophilic leukaemia cells. Saturable uptake of PEA and AEA into both cell
      lines were demonstrated with apparent K(M) values of 28 microM (PEA) and 10
      microM (AEA) in Neuro-2a cells, and 30 microM (PEA) and 9.3 microM (AEA) in RBL
      2H3 cells. Both PEA and AEA uptake showed temperature-dependence but only the AEA
      uptake was sensitive to treatment with Pronase and phenylmethylsulfonyl fluoride.
      The AEA uptake was inhibited by AM404, 2-arachidonoylglycerol (2-AG), R1- and S1
      methanandamide, arachidonic acid and olvanil with similar potencies for the two
      cell types. PEA, up to a concentration of 100 microM, did not affect AEA uptake
      in either cell line. AEA, 2-AG, arachidonic acid, R1-methanandamide, (9)-THC, and
      cannabidiol inhibited PEA transport in both cell lines. The non-steroidal anti
      inflammatory drug indomethacin inhibited the AEA uptake but had very weak effects
      on the uptake of PEA. From these data, it can be concluded that PEA is
      transported in to cells both by passive diffusion and by a facilitated transport
      that is pharmacologically distinguishable from AEA uptake.

PMID- 11309247
TI  - Tetrapentylammonium block of chloramine-T and veratridine modified rat brain type
      IIA sodium channels.
AB  - Tetrapentylammonium (TPeA) block of rat brain type IIA sodium channel alpha
      subunit was studied using whole cell patch clamp. Results indicate that TPeA
      blocks the inactivating brain sodium channel in a potential and use-dependent
      manner similar to that of the cardiac sodium channel. Removal of inactivation
      using chloramine-T (CT) unmasks a time-dependent block by TPeA consistent with
      slow blocking kinetics. On the other hand, no time dependence is observed when
      inactivation is abolished by modification with veratridine. TPeA does not bind in
      a potential-dependent fashion to veratridine-modified channels and does not
      significantly affect gating of veratridine-modified channels suggesting that high
      affinity binding of TPeA to the brain sodium channel is lost after veratridine
      modification.

PMID- 11309248
TI  - Direct inhibitory effect of digitalis on progesterone release from rat granulosa
      cells.
AB  - Digoxin (10(-7) - 10(-5) M) or digitoxin (10(-7) - 10(-5) M) decreased the basal
      and human chorionic gonadotropin (hCG)-stimulated release of progesterone from
      rat granulosa cells. Digoxin (10(-5) M) or digitoxin (10(-5) M) attenuated the
      stimulatory effects of forskolin and 8-bromo-cyclic 3' : 5'-adenosine
      monophosphate (8-Br-cAMP) on progesterone release from rat granulosa cells.
      Digoxin (10(-5) M) or digitoxin (10(-5) M) inhibited cytochrome P450 side chain
      cleavage enzyme (cytochrome P450(scc)) activity (conversion of 25-hydroxyl
      cholesterol to pregnenolone) in rat granulosa cells but did not influence the
      activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Neither progesterone
      production nor P450scc activity in rat granulosa cells was altered by the
      administration of ouabain. Digoxin (10(-5) M) or digitoxin (10(-5) M), but not
      ouabain, decreased the expression of P450scc and steroidogenic acute regulatory
      (StAR) protein in rat granulosa cells. The present results suggest that digoxin
      and digitoxin decrease the progesterone release by granulosa cells via a
      Na(+),K(+)-ATPase-independent mechanism involving the inhibition of post-cyclic
      AMP pathway, cytochrome P450scc and StAR protein functions.

PMID- 11309249
TI  - Involvement of PACAP receptor in primary afferent fibre-evoked responses of
      ventral roots in the neonatal rat spinal cord.
AB  - The role of PACAP receptor in nociceptive transmission was investigated in vitro
      using maxadilan, a PACAP receptor selective agonist and max.d.4, a PACAP receptor
      selective antagonist. Potentials, from a ventral root (L3 - L5) of an isolated
      spinal cord preparation or a spinal cord - saphenous nerve - skin preparation
      from 0 - 3-day-old rats, were recorded extracellularly. In the isolated spinal
      cord preparation, single shock stimulation of a dorsal root at C-fibre strength
      induced a slow depolarizing response lasting about 30 s (slow ventral root
      potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath
      application of max. d.4 (0.01 - 3 microM) inhibited the slow VRP in a
      concentration-dependent manner. In the spinal cord - saphenous nerve - skin
      preparation, application of capsaicin (0.1 microM) to the skin evoked a
      depolarization of the ventral root. This response was also depressed by max.d.4
      (1 microM). Application of maxadilan evoked a long-lasting depolarization in a
      concentration-dependent manner in the spinal cord preparation. In the presence of
      max.d.4 (0.3 microM), the concentration response curve of maxadilan was shifted
      to the right. Reverse transcription-polymerase chain reaction (RT - PCR)
      experiments demonstrated the existence of PACAP receptor and VPAC(2) receptor in
      the neonatal rat spinal cord and [(125)I]-PACAP27 binding was displaced almost
      completely by maxadilan and max.d.4, but not by vasoactive intestinal peptide
      (VIP). These data indicate that PACAP receptor is dominantly distributed in the
      neonatal rat spinal cord. The present study suggests that PACAP receptor may play
      an excitatory role in nociceptive transmission in the neonatal rat spinal cord.

PMID- 11309250
TI  - Phenolic antioxidants trolox and caffeic acid modulate the oxidized LDL-induced
      EGF-receptor activation.
AB  - Oxidized low density lipoproteins (oxLDL) are thought to play a major role in
      atherosclerosis. OxLDL act in part through alteration of intracellular signalling
      pathways in cells of the vascular wall. We recently reported that the EGF
      receptor (EGFR) signalling pathway is activated by lipid peroxidation products
      (among them 4-hydroxynonenal, 4-HNE) contained in oxLDL. The use of phenolic
      antioxidants, such as trolox, alpha-tocopherol, caffeic acid and tyrphostins A
      25, A-46 or A-1478, showed that the oxLDL-induced EGFR activation is constituted
      by two separate components, the first (early) one being antioxidant-insensitive,
      the second (late) being antioxidant-sensitive. 4-HNE derivatization of EGFR and
      EGFR activation induced by exogenous 4-HNE, suggest that the early (0.5 - 3 h)
      component of oxLDL-induced EGFR activation is mediated (at least in part) by 4
      HNE (and possibly by other oxidized lipids). This early component is antioxidant
      insensitive. The second component (4 - 5 h) of the oxLDL-induced EGFR activation
      is antioxidant-sensitive, since it is blocked by antioxidants such as trolox,
      caffeic acid or PDTC, which act by blocking the cellular oxidative stress
      (H(2)O(2) generation) evoked by oxLDL. Conversely, exogenous H(2)O(2) induced
      EGFR autophosphorylation (thus mimicking the second component) and was also
      inhibited by antioxidants. This effect is mediated in part through inhibition by
      oxidative stress of protein tyrosine phosphatases involved in EGFR
      dephosphorylation.

PMID- 11309251
TI  - Pharmacological characterization of serotonin receptor subtypes modulating
      primary afferent input to deep dorsal horn neurons in the neonatal rat.
AB  - Spinal cord slices and whole-cell patch clamp recordings were used to investigate
      the effects of serotonergic receptor ligands on dorsal root-evoked synaptic
      responses in deep dorsal horn (DDH) neurons of the neonatal rat at postnatal days
      (P) 3 - 6 and P10 - 14. Bath applied 5-hydroxytryptamine (5-HT) potently
      depressed synaptic responses in most neurons. Similarly, the 5-HT(1/7) receptor
      agonist, 5-carboxamidotryptamine (5-CT) depressed synaptic responses. This action
      was probably mediated by 5-HT(1A) receptor activation, since it occurred in the
      presence of the 5-HT(7) receptor antagonist clozapine and was not observed in the
      presence of NAN-190, a 5-HT(1A) receptor antagonist. In the absence of any
      agonist, 5-HT(1A) receptor antagonists often facilitated synaptic responses,
      suggesting that there is sufficient endogenous 5-HT to tonically activate 5
      HT(1A) receptors. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the 5
      HT(1A/7) receptor agonist, facilitated synaptic responses, an action probably
      mediated by 5-HT(7) receptors, since the facilitation could be reversed by
      subsequent application of the 5-HT(7) receptor antagonist clozapine. Agonists for
      the 5-HT(1B), 5-HT(2) and 5-HT(3) receptors exerted only modest modulatory
      actions. A pharmacological analysis of the depression evoked by 5-HT suggested an
      action partly mediated by 5-HT(1A) receptor activation, since antagonism of the 5
      HT(1A) receptor with NAN-190 or WAY-100635 partly reversed 5-HT-evoked
      depression. In comparison, 5-HT(7) receptor activation could account for much of
      the 5-HT-evoked facilitation. We conclude that 5-HT is capable of modulating
      sensory input onto DDH neurons via several receptor subtypes, producing both
      facilitatory and depressant actions. Also, the actions of most receptor ligands
      on the evoked responses were similar within the first 2 postnatal weeks.

PMID- 11309252
TI  - An endogenous 5-HT(7) receptor mediates pigment granule dispersion in Xenopus
      laevis melanophores.
AB  - Melatonin (5-methoxy N-acetyltryptamine) and serotonin (5-HT) exert rapid, but
      opposite effects on pigment granule distribution in Xenopus laevis melanophores.
      Low concentrations of melatonin (10(-11) - 10(-9) M) cause a dramatic perinuclear
      aggregation of the melanin-containing granules, while 5-HT (10(-8) - 10(-5) M)
      disperses pigment granules throughout the cell. The present study found that
      pharmacological doses of melatonin (> or =10(-6) M) induced a time- and
      concentration-dependent pigment granule dispersion, which was mediated by an
      endogenous melanophore 5-HT receptor. 5-HT produced a concentration-dependent
      elevation of melanophore cyclic AMP, and 5-HT-induced dispersion was blocked by
      H89 (10(-4) M), an inhibitor of protein kinase A (PKA), but not by a PKC
      inhibitor (Ro 31-8220, 10(-5) M), indicating a vital role for cyclic AMP in 5-HT
      induced dispersion. 5-HT-mediated dispersion was not blocked by antagonists
      selective for G(s)-coupled 5-HT(4) (GR113808) or 5-HT(6) (Ro 04-6790, Ro 63-0563,
      olanzepine) receptors, nor by 5-HT(1 - 3) (pindolol, ketanserine, metoclopramide,
      MDL72222, tropisetron) receptor antagonists, but was inhibited by a selective 5
      HT(7) receptor antagonist, DR4004, and other antagonists with a high affinity for
      5-HT(7) receptors. The rank order of antagonist potency was: risperidone (mean
      pK(B) 7.82)>methiothepin (7.43)>DR4004 (6.92)>mesulergine (6.83)>methysergide
      (6.60)>[+/-]-sulpiride (5.81)>spiperone (5.52). The agonist potency order [mean
      pEC(50), 5-CT (8.68)>5-HT (7.13)>5-MT (6.94)>8-OH-DPAT (4.79)>sumatriptan (<4)]
      was also consistent with an action on 5-HT(7) receptors. RT - PCR confirmed that
      melanophores express 5-HT(7) receptor mRNA. The pigment dispersing effect of high
      melatonin concentrations in melanophores is most likely mediated by activation of
      5-HT(7) receptors. Conceivably some of the effects attributed to pharmacological
      doses of melatonin in mammals may be mediated by activation of 5-HT(7) receptors.

PMID- 11309253
TI  - Reduction of opioid dependence by the CB(1) antagonist SR141716A in mice:
      evaluation of the interest in pharmacotherapy of opioid addiction.
AB  - Several compounds, mainly opioid agonists such as methadone, are currently used
      for long term medication of heroin addicts. Nevertheless, these maintenance
      treatments have the disadvantage to induce a dependence to another opiate. As
      interactions between opioid and cannabinoid systems have been demonstrated, the
      ability of the CB(1) antagonist, SR141716A to reduce morphine-induced addiction
      was investigated. The effects of SR141716A on the rewarding responses of morphine
      were evaluated in the place conditioning paradigm. No significant conditioned
      preference or aversion were observed after repeated treatment with the CB(1)
      antagonist alone. However, SR141716A was able to antagonize the acquisition of
      morphine-induced conditioned place preference. SR141716A was co-administered with
      morphine for 5 days, and the withdrawal syndrome was precipitated by naloxone
      administration. A reduction in the incidence of two main signs of abstinence: wet
      dog shakes and jumping was observed while the other were not significantly
      modified. In contrast, an acute injection of the CB(1) antagonist just before
      naloxone administration was unable to modify the incidence of the behavioural
      manifestations of the withdrawal, suggesting that only chronic blockade of CB(1)
      receptors is able to reduce morphine-induced physical dependence. Several
      biochemical mechanisms could explain the reduction of opioid dependence by CB(1)
      antagonists. Whatever the hypotheses, this study supports the reported
      interaction between the endogenous cannabinoid and opioid systems, and suggests
      that SR 141716A warrants further investigations for a possible use in opioid
      addiction.

PMID- 11309254
TI  - Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction
      and inverse agonism of nebivolol in human myocardium.
AB  - Intrinsic activity and beta(1)-selectivity are important features of beta
      blockers in the treatment of patients with coronary syndromes and heart failure.
      In human myocardium, intrinsic activity and beta(1)-selectivity of the novel beta
      adrenoceptor antagonist nebivolol have not yet been determined. The study
      examines intrinsic activity, beta-adrenoceptor-G-protein coupling and beta(1)
      selectivity of nebivolol and bisoprolol in human ventricular myocardium.
      Furthermore, intrinsic activity of both compounds is compared to the one of
      bucindolol, carvedilol and metoprolol in human atrial myocardium. Radioligand
      binding studies ([(125)I]-lodocyanopindolol) were performed on membrane
      preparations of human failing and nonfailing myocardium and on COS-7 cells
      transfected with human beta(1)- and beta(2)-adrenoceptors, respectively.
      Functional experiments were carried out on isolated muscle preparations of human
      left ventricular and right atrial myocardium from failing and nonfailing hearts.
      Radioligand binding studies reveal 3 - 4 fold beta(1)-selectivity for nebivolol
      and 16 - 20 fold beta(1)-selectivity for bisoprolol in human myocardium. In COS-7
      cells, beta(1)-selectivity is 3 fold for nebivolol and 15 fold for bisoprolol.
      Neither the binding of nebivolol nor of bisoprolol is affected by the presence of
      guanylylimidodiphosphate (Gpp(NH)p). Nebivolol and bisoprolol exert similar
      inverse agonist activity in human ventricular as well as atrial myocardium. In
      atrial myocardium, inverse agonism of both compounds is higher compared to
      bucindolol, equal to carvedilol and lower compared to metoprolol. Favourable
      haemodynamic effects of nebivolol in humans are not due to beta(1)-selectivity or
      partial agonist activity of this agent. Other mechanisms, i.e. the production of
      nitric oxide, may thus be responsible for its unique haemodynamic profile.

PMID- 11309255
TI  - Contribution of alpha(2) receptor subtypes to nerve injury-induced pain and its
      regulation by dexmedetomidine.
AB  - There is evidence that noradrenaline contributes to the development and
      maintenance of neuropathic pain produced by trauma to a peripheral nerve. It is,
      however, unclear which subtype(s) of alpha adrenergic receptors (AR) may be
      involved. In addition to pro-nociceptive actions of AR stimulation, alpha(2) AR
      agonists produce antinociceptive effects. Here we studied the contribution of the
      alpha(2) AR subtypes, alpha(2A), alpha(2B) and alpha(2C) to the development of
      neuropathic pain. We also examined the antinociceptive effect produced by the
      alpha(2) AR agonist dexmedetomidine in nerve-injured mice. The studies were
      performed in mice that carry either a point (alpha(2A)) or a null (alpha(2B) and
      alpha(2C)) mutation in the gene encoding the alpha(2) AR. To induce a neuropathic
      pain condition, we partially ligated the sciatic nerve and measured changes in
      thermal and mechanical sensitivity. Baseline mechanical and thermal withdrawal
      thresholds were similar in all mutant and wild-type mice; and, after peripheral
      nerve injury, all mice developed comparable hypersensitivity (allodynia) to
      thermal and mechanical stimulation. Dexmedetomidine reversed the allodynia at a
      low dose (3 microg kg(-1), s.c.) and produced antinociceptive effects at higher
      doses (10 - 30 microg kg(-1)) in all groups except in alpha(2A) AR mutant mice.
      The effect of dexmedetomidine was reversed by intrathecal, but not systemic,
      injection of the alpha(2) AR antagonist RS 42206. These results suggest that
      neither alpha(2A), alpha(2B) nor alpha(2C) AR is required for the development of
      neuropathic pain after peripheral nerve injury, however, the spinal alpha(2A) AR
      is essential for the antinociceptive effects of dexmedetomidine.

PMID- 11309256
TI  - Cerebral vasoconstriction produced by vasopressin in conscious goats: role of
      vasopressin V(1) and V(2) receptors and nitric oxide.
AB  - To examine the role of vasopressin V(1) and V(2) receptors, nitric oxide and
      prostanoids in the cerebrovascular effects of arginine vasopressin, cerebral
      blood flow was electromagnetically measured in awake goats. In 16 animals,
      vasopressin (0.03 - 1 microg), injected into the cerebral circulation, caused
      increments of resting cerebrovascular resistance which ranged from 18% (0.03
      microg, P<0.01) to 79% (1 microg, P<0.01). Desmopressin (0.03 - 1 microg, four
      goats) did not affect significantly cerebrovascular resistance. The
      cerebrovascular resistance increases by vasopressin were reduced significantly by
      the antagonist for vasopressin V(1) receptors d(CH(2))(5)Tyr(Me)-AVP in a rate
      depending way (five (six goats) and 15 (four goats) microg min(-1)), and by the
      mixed antagonist for vasopressin V(1) and V(2) receptors desGly-d(CH(2))(5)-D
      Tyr(Et)Val-AVP (5 microg min(-1), four goats), and they were not significantly
      affected by the antagonist for vasopressin V(2) receptors d(CH(2))(5), D-Ile(2),
      Ile(4)-AVP (5 microg min(-1), four goats). The inhibitor of nitric oxide
      synthesis N(w)-nitro-L-arginine methyl ester (L-NAME, 47 mg kg(-1) i.v., five
      goats) augmented cerebrovascular resistance by 130% (P<0.01), and for 24 h after
      this treatment the cerebrovascular effects of vasopressin were potentiated. The
      inhibitor of cyclo-oxygenase meclofenamate (6 mg kg(-1) i.v., five goats) did not
      modify significantly resting haemodynamic variables measured or the
      cerebrovascular effects of vasopressin. Therefore, the vasopressin-induced
      cerebral vasoconstriction may be mediated by vasopressin V(1) receptors, without
      involvement of vasopressin V(2) receptors, and may be modulated by nitric oxide
      but not by prostanoids.

PMID- 11309257
TI  - Role of nitric oxide synthases in the infarct size-reducing effect conferred by
      heat stress in isolated rat hearts.
AB  - Nitric oxide (NO) donors are known to induce both delayed cardioprotection and
      myocardial heat stress protein (HSP) expression. Moreover, heat stress (HS),
      which also protects myocardium against ischaemic damages, is associated with a NO
      release. Therefore, we have investigated the implication of NO in HS-induced
      resistance to myocardial infarction, in the isolated rat heart model. Rats were
      divided in six groups (n=10 in each group), subjected or not to heat stress (42
      degrees C internal temperature, 15 min) and treated or not with nitro-L-arginine
      methylester (L-NAME) a non-selective inhibitor of NO synthase isoforms, or L-N(6)
      (1-imino-ethyl)lysine (L-NIL), a selective inhibitor of the inducible NO
      synthase. Twenty-four hours after heat stress, their hearts were isolated,
      retrogradely perfused, and subjected to a 30-min occlusion of the left coronary
      artery followed by 120 min of reperfusion. Infarct-to-risk ratio was
      significantly reduced in HS (18.7+/-1.6%) compared to Sham (33.0+/-1.7%) hearts.
      This effect was abolished in L-NAME-treated (41.7+/-3.1% in HS+L-NAME vs 35.2+/
      3.0% in Sham+L-NAME ) and L-NIL-treated (36.1+/-3.4% in HS+L-NIL vs 42.1+/-4.6%
      in Sham+L-NIL) groups. Immunohistochemical analysis of myocardial HSP 27 and 72
      showed an HS-induced increase of these proteins, which was not modified by L-NAME
      pretreatment. We conclude that NO synthases, and in particular the inducible
      isoform, appear to play a role in the heat stress-induced cardioprotection,
      independently of HSP 27 and 72 levels. Further investigations are required to
      elucidate the precise role of HSPs in this adaptive response.

PMID- 11309258
TI  - Existence of different alpha(1)-adrenoceptor subtypes in junctional and
      extrajunctional neurovascular regions in canine splenic arteries.
AB  - The present study attempted to characterize the alpha(1)-adrenoceptor subtypes
      mediating vasoconstrictor responses to administered and nerve stimulation-evoked
      noradrenaline (NA) release in the isolated and perfused canine splenic artery. A
      previous study demonstrated that periarterial electrical nerve stimulation (30 s
      trains of pulses at a frequency of 1, 4 or 10 Hz) induced a double peaked
      vasoconstriction consisting of an initial transient, predominantly P2X
      purinoceptor-mediated constriction followed by a prolonged, mainly alpha(1)
      adrenoceptor-mediated response in the canine splenic artery. The effects of
      alpha(1)-adrenoceptor subtype antagonists on neuronally-mediated second peaked
      vasoconstrictions were analysed. BMY 7378 (10 - 100 nM), a selective alpha(1D)
      adrenoceptor antagonist produced a dose-dependent inhibition of the second peak
      responses at all frequencies used. BMY 7378 (100 nM) reduced these responses by
      approximately 30%. Exposure of tissues to chloroethylclonidine (CEC, 60 microM),
      a selective alpha(1B)-adrenoceptor antagonist attenuated the second peak response
      by approximately 60%, even in the presence of BMY 7378 (100 nM). On the other
      hand, WB 4101 (100 nM), a selective alpha(1A)-adrenoceptor antagonist potentiated
      nerve-stimulation-evoked double peaked vasoconstrictions, especially at low
      frequencies (1 and 4 Hz). Vasoconstrictor responses to administered NA were dose
      dependently antagonized by WB 4101 (10 - 100 nM), but were not significantly
      affected by either BMY 7378 (10 - 100 nM) or by CEC (60 microM). The present
      results indicate that NA released from sympathetic nerves may junctionally exert
      its vasoconstrictor effect via activation of postjunctional alpha(1B)- and in
      part alpha(1D)-adrenoceptors, whereas exogenous NA extrajunctionally activates
      alpha(1A)-adrenoceptors to produce its vascular action in canine splenic
      arteries.

PMID- 11309259
TI  - Characteristics of AMPA receptor-mediated responses of cultured cortical and
      spinal cord neurones and their correlation to the expression of glutamate
      receptor subunits, GluR1-4.
AB  - Electrophysiological recordings have been used to characterize responses mediated
      by AMPA receptors expressed by cultured rat cortical and spinal cord neurones.
      The EC(50) values for AMPA were 17 and 11 microM, respectively. Responses of
      cortical neurones to AMPA were inhibited competitively by NBQX (pK(i)=6.6). Lower
      concentrations of NBQX (< or =1 microM) also potentiated the plateau responses of
      spinal cord neurones to AMPA, which could be attributed to a depression of
      desensitization to AMPA. GYKI 52466 inhibited responses of spinal cord neurones
      to AMPA to about twice the extent of responses of cortical neurones. Blockade of
      AMPA receptor desensitization by cyclothiazide (CTZ) potentiated responses of
      spinal cord neurones (6.8 fold) significantly more than responses of cortical
      neurones (4.8 fold). Responses of cortical neurones to KA were potentiated 3.5
      fold by CTZ, while responses of spinal cord neurones were unaffected. Ultra-fast
      applications of AMPA to outside-out patches showed responses of spinal cord
      neurones desensitized by 97.5% and exhibit marked inward rectification, whereas
      cortical neurones desensitized by 91% and exhibited slight outward rectification.
      The time constants of deactivation and desensitization were about twice as fast
      in spinal cord than cortical neurones. In cortical neurones, single-cell RT - PCR
      showed GluR2 and GluR1 accounted for 91% of all subunits and were expressed
      together in 67% of neurones, predominantly as the flip variants (78%). GluR2 was
      detected alone in 24% of neurones. GluR3 and GluR4 were present in only 14 and
      29% of neurones, respectively. For spinal cord neurones, GluR4(o) was detected in
      81% of neurones, whereas predominantly flop versions of GluR1, 2 and 3 were
      detected in 38, 13 and 13% of neurones, respectively. These expression patterns
      are related to the respective pharmacological and mechanistic properties.

PMID- 11309260
TI  - Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L
      isothiocitrulline-containing dipeptides.
AB  - The aim of this study was to investigate the structure-activity relationship of S
      alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified
      recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of
      these compounds on cytokine-induced NO production by human DLD-1 cells. In an in
      vitro assay, S-methyl-L-isothiocitrulline (L-MIT) was slightly selective for
      human neuronal NOS (nNOS) over the inducible (iNOS) or endothelial (eNOS)
      isozyme, but the combination of a hydrophobic L-amino acid (L-Phe, L-Leu or L
      Trp) with L-MIT dramatically altered the inhibition pattern to give selective
      iNOS inhibitors. Introduction of a hydroxy, nitro, amino or methoxy group at the
      para position of the aromatic ring of L-MIT-L-Phe (MILF) decreased the
      selectivity and inhibitory potency. A longer or larger S-alkyl group also
      decreased the selectivity and potency. Dixon analysis showed that all of the
      dipeptides were competitive inhibitors of the three isoforms of human NOS. The
      enzymatic time course curves indicated that MILF was a slow binding inhibitor of
      human iNOS. These results suggest that the human NOS isozymes have different
      sized cavities in the binding site near the position to which the C-terminal of L
      arginine binds, and the cavity of iNOS is hydrophobic. Interestingly, L-MIT-D-Phe
      (MIDF) showed little inhibitory activity or selectivity, suggesting that the
      cavity of human iNOS is located in a well-defined direction from the alpha carbon
      atom. NO production in cytokine-stimulated human DLD-1 cells was measured with a
      fluorescent indicator, DAF-FM. MILF, L-MIT-L-Trp(-CHO) (MILW) and L-MIT-L-Tyr
      (MILY) showed more potent activity than L-MIT in this whole-cell assay. Thus, S
      alkyl-L-isothiocitrulline-containing dipeptides are selective inhibitors of human
      iNOS, and work efficiently in cell-based assay.

PMID- 11309261
TI  - Allosteric modulation of [3H]-CGP39653 binding through the glycine site of the
      NMDA receptor: further studies in rat and human brain.
AB  - Binding of D,L-(E)-2-amino-4-[(3)H]-propyl-5-phosphono-3-pentenoic acid ([(3)H]
      CGP39653), a selective antagonist at the glutamate site of the NMDA receptor, is
      modulated by glycine in rat brain tissue. We have further investigated this
      phenomenon in rodent and human brain by means of receptor binding and
      quantitative autoradiography techniques. In rat cerebral cortical membranes the
      glycine antagonist 3-[2-(Phenylaminocarbonyl)ethenyl]-4,6-dichloro-indole-2
      carboxylic acid sodium salt (GV150526A) did not change basal [(3)H]-CGP39653
      binding, but competitively reversed the high affinity component of [(3)H]
      CGP39653 binding inhibition by glycine, with a pK(B) value of 8.38, in line with
      its affinity for the glycine site (pK(i)=8.49 vs. [(3)H]-glycine). Glycine (10
      microM) significantly decreased [(3)H]-CGP39653 affinity for the NMDA receptor
      (with no change in the B(max)), whereas enhanced L-glutamate affinity (P<0.05,
      paired-samples Student's t-test). In rat brain sections the addition of GV150526A
      (30 microM) to the incubation medium increased [(3)H]-CGP39653 binding to 208% of
      control (average between areas), indicating the presence of endogenous glycine.
      The enhancement presented significant regional differences (P<0.05, two-way
      ANOVA), with striatum higher than cerebral cortex (282 and 187% of control,
      respectively; P<0.05, Fisher's LSD). On the contrary, there was not any
      significant variation in affinity values of [(3)H]-CGP39653, L-glutamate, glycine
      and GV150526A in striatal and cortical membranes. These results confirmed the
      existence of regionally distinct NMDA receptors subtypes with different
      glycine/glutamate allosteric modulation. Whole brain autoradiography revealed an
      uneven distribution of [(3)H]-CGP39653 binding sites in human brain. High levels
      of binding were determined in hippocampus and in cingulate, frontoparietal and
      insular cortex. Intermediate to low levels of binding were found in diencephalic
      nuclei and basal ganglia. [(3)H]-CGP39653 binding was increased to 216% of
      control (mean between areas) by 30 microM GV150526A. The enhancement, however,
      did not present significant regional differences. These results introduce
      GV150526A as a useful tool to identify NMDA receptor subtypes by means of
      receptor autoradiography; moreover, they demonstrate that the allosteric
      inhibition of [(3)H]-CGP39653 binding by glycine parallels an increase in
      receptor affinity to the endogenous ligand L-glutamate. Finally, this study
      provides the first detailed anatomical description of the regional distribution
      of [(3)H]-CGP39653 binding sites in human brain.

PMID- 11309262
TI  - Sibutramine reduces feeding, body fat and improves insulin resistance in dietary
      obese male Wistar rats independently of hypothalamic neuropeptide Y.
AB  - We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake
      inhibitor sibutramine on feeding and body weight in a rat model of dietary
      obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY)
      neurones. Chow-fed and dietary-obese (DIO) male Wistar rats were given
      sibutramine (3 mg kg(-1) day(-1) p.o.) or deionized water for 21 days.
      Sibutramine decreased food intake throughout the treatment period in both dietary
      obese rats (P<0.0001) and lean rats (P<0.0001). Weight gain was reduced so that
      final body weight was 10% lower in dietary-obese (P<0.005) and 8% lower in lean
      (P<0.05) rats versus their untreated controls. Plasma leptin concentration was
      lower in sibutramine-treated dietary-obese rats (P<0.05), and in treated lean
      rats (P<0.05). Using the homeostasis model assessment (HOMA) as a measure of
      insulin resistance, untreated DIO rats were significantly more insulin resistant
      than controls (P<0.005), and this was corrected by sibutramine treatment
      (P<0.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of
      hypothalamic nuclei were significantly altered by sibutramine compared to
      untreated controls. The hypophagic and anti-obesity effects of sibutramine in
      dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY
      neurones.

PMID- 11309264
TI  - Structural requirements for voltage-dependent block of muscle sodium channels by
      phenol derivatives.
AB  - We have studied the effects of four different phenol derivatives, with methyl and
      halogen substituents, on heterologously expressed human skeletal muscle sodium
      channels, in order to find structural determinants of blocking potency. All
      compounds blocked skeletal muscle sodium channels in a concentration-dependent
      manner. The methylated phenol 3-methylphenol and the halogenated phenol 4
      chlorophenol blocked sodium currents on depolarization from -100 mV to 0 mV with
      IC(50) values of 2161 and 666 microM respectively. Methylation of the halogenated
      compound further increased potency, reducing the IC(50) to 268 microM in 2-methyl
      4-chlorophenol and to 150 microM in 3,5-dimethyl-4-chlorophenol. Membrane
      depolarization before the test depolarization increased sodium channel blockade.
      When depolarizations were started from -70 mV or when a 2.5 s prepulse was
      introduced before the test pulse inducing slow inactivation, the IC(50) was
      reduced more than 3 fold in all compounds. The values of K(D) for the fast
      inactivated state derived from drug-induced shifts in steady-state availability
      curves were 14 microM for 3,5-dimethyl-4-chlorophenol, 19 microM for 2-methyl-4
      chlorophenol, 26 microM for 4-chlorophenol and 115 microM for 3-methylphenol. All
      compounds accelerated the current decay during depolarization and slowed recovery
      from fast inactivation. No relevant frequency-dependent block after depolarizing
      pulses applied at 10, 50 and 100 Hz was detected for any of the compounds. All
      the phenol derivatives that we examined are effective blockers of skeletal muscle
      sodium channels, especially in conditions that are associated with membrane
      depolarization. Blocking potency is increased by halogenation and by methylation
      with increasing numbers of methyl groups.

PMID- 11309263
TI  - Differential modulation of endothelin ligand-induced contraction in isolated
      tracheae from endothelin B (ET(B)) receptor knockout mice.
AB  - The role of endothelin B (ET(B)) receptors in mediating ET ligand-induced
      contractions in mouse trachea was examined in ET(B) receptor knockout animals.
      Autoradiographic binding studies, using [(125)I]-ET-1, confirmed the presence of
      ET(A) receptors in tracheal and bronchial airway smooth muscle from wild-type
      (+/+) and homozygous recessive (-/-) ET(B) receptor knockout mice. In contrast,
      ET(B) receptors were not detected in airway tissues from (-/-) mice. In tracheae
      from (+/+) mice, the rank order of potencies of the ET ligands was sarafotoxin
      (Stx) S6c>ET-1>ET-3; Stx S6c had a lower efficacy than ET-1 or ET-3. In tissues
      from (-/-) mice there was no response to Stx S6c (up to 0.1 microM), whereas the
      maximum responses and potencies of ET-1 and ET-3 were similar to those in (+/+)
      tracheae. ET-3 concentration-response curve was biphasic in (+/+) tissues (via
      ET(A) and ET(B) receptor activation), and monophasic in (-/-) preparations (via
      stimulation of only ET(A) receptors). In (+/+) preparations SB 234551 (1 nM), an
      ET(A) receptor-selective antagonist, inhibited the secondary phase, but not the
      first phase, of the ET-3 concentration-response curve, whereas A192621 (100 nM),
      an ET(B) receptor-selective antagonist, had the opposite effect. In (-/-) tissues
      SB 234551 (1 nM), but not A192621 (100 nM), produced a rightward shift in ET-3
      concentration-response curves. The results confirm the significant influence of
      both ET(A) and ET(B) receptors in mediating ET-1-induced contractions in mouse
      trachea. Furthermore, the data do not support the hypothesis of atypical ET(B)
      receptors. In this preparation ET-3 is not an ET(B) receptor-selective ligand,
      producing contractions via activation of both ET(A) and ET(B) receptors.

PMID- 11309265
TI  - Lysosphingolipid receptor-mediated diuresis and natriuresis in anaesthetized
      rats.
AB  - Lysosphingolipids such as sphingosine-1-phosphate (SPP) and
      sphingosylphosphorylcholine (SPPC) can act on specific G-protein-coupled
      receptors. Since SPP and SPPC cause renal vasoconstriction, we have investigated
      their effects on urine and electrolyte excretion in anaesthetized rats. Infusion
      of SPP (1 - 30 microg kg(-1) min(-1)) for up to 120 min dose-dependently but
      transiently (peak after 15 min, disappearance after 60 min) reduced renal blood
      flow without altering endogenous creatinine clearance. Nevertheless, infusion of
      SPP increased diuresis, natriuresis and calciuresis and, to a lesser extent,
      kaliuresis. These tubular lysosphingolipid effects developed more slowly (maximum
      after 60 - 90 min) and also abated more slowly upon lysosphingolipid washout than
      the renovascular effects. Infusion of SPPC, sphingosine and glucopsychosine (3 -
      30 microg kg(-1) min(-1) each) caused little if any alterations in renal blood
      flow but also increased diuresis, natriuresis and calciuresis and, to a lesser
      extent, kaliuresis. Pretreatment with pertussis toxin (10 microg kg(-1) 3 days
      before the acute experiment) abolished the renovascular and tubular effects of 30
      microg kg(-1) min(-1) SPP. These findings suggest that lysosphingolipids are a
      hitherto unrecognized class of endogenous modulators of renal function. SPP
      affects renovascular tone and tubular function via receptors coupled to G(i)-type
      G-proteins. SPPC, sphingosine and glucopsychosine mimic only the tubular effects
      of SPP, and hence may act on distinct sites.

PMID- 11309266
TI  - Heterogeneity of neuronal nicotinic acetylcholine receptors in 5-HT-containing
      chemoreceptor cells of the chicken aorta.
AB  - The effects of nicotinic agonists and antagonists on whole-cell currents and 5
      hydroxytryptamine (5-HT) release were studied in order to characterize nicotinic
      ACh receptors on the 5-HT-containing chemoreceptor cells of the chicken aorta.
      ACh, nicotine and dimethylphenylpiperazinium (DMPP) evoked concentration
      dependent inward currents accompanied by increases in current noise at a holding
      potential of -70 mV. The peak amplitude of the current response to DMPP was 50%
      larger than that to either nicotine or ACH: Hexamethonium, alpha - bungarotoxin
      (alpha - BTX) and methyllycaconitine decreased nicotine-induced inward currents
      in a concentration-dependent manner. Although hexamethonium (0.1 mM) abolished
      the current response to nicotine (30 microM), a high concentration (1 microM) of
      alpha - BTX decreased it only by about 30% of the control response.
      Methyllycaconitine (0.1 microM) decreased the current response to nicotine to the
      same extent as did alpha - BTX whilst a high concentration (10 microM) abolished
      the response. ACh, nicotine and DMPP caused concentration-dependent increases in
      5-HT output from the thoracic aorta which effect was blocked by hexamethonium
      (0.1 mM). Pre-treatment with alpha - BTX (1 microM) for 30 min reduced the output
      of 5-HT induced by ACh to 70% of the control response. It is suggested that
      neuronal nicotinic ACh receptors, sensitive and insensitive to alpha - BTX, are
      present on the chemoreceptor cells of the chicken aorta, the activation of which
      causes the release of 5-HT.

PMID- 11309267
TI  - 5-HT(4) receptors mediating enhancement of contractility in canine stomach; an in
      vitro and in vivo study.
AB  - We aimed to study 5-HT(4) receptors in canine stomach contractility both in vivo
      and in vitro. In anaesthetized Beagle dogs, the selective 5-HT(4) receptor
      agonist prucalopride (i.v.) induced dose-dependent tonic stomach contractions
      under isobaric conditions, an effect that was antagonized by the selective 5
      HT(4) receptor antagonist GR 125487 (10 microg kg(-1), i.v.). Electrical field
      stimulation (EFS) of corpus longitudinal muscle strips resulted in atropine- and
      tetrodotoxin-sensitive contractions (L-NOARG (0.1 mM) present in all organ bath
      solutions). Prucalopride increased these contractions (maximal response after
      single-dose addition (0.3 microM): 165% of initial value, or after cumulative
      addition: 188%). In the presence of methysergide (3 microM), 5-HT also increased
      EFS-contractions (after single-dose addition (0.3 microM): increase to 192%,
      after cumulative addition: 148%). The selective 5-HT(4) receptor antagonists GR
      113808 (0.1 microM) or GR 125487 (10 nM) antagonized the prucalopride (0.3
      microM)-induced contraction increments. When EFS-induced contractions were
      blocked by atropine or tetrodotoxin, prucalopride was ineffective. In the
      presence of methysergide (3 microM), the contraction increases to 5-HT (0.3
      microM) were prevented by GR 113808 (0.1 microM). The prucalopride curve (pEC(50)
      7.9) was shifted in parallel to the right by GR 113808 3 nM (pA(2) 9.4). In the
      presence of methysergide (3 microM), the curve to 5-HT (pEC(50) 8.1) was
      competitively antagonized by GR 113808, yielding a Schild slope of 0.8+/-0.2
      (pK(B) of 9.1 with unit Schild slope). In corpus circular muscle strips, the
      prucalopride (0.3 microM)-induced augmentation of EFS-contractions (258%) was
      also prevented by GR 113808 (0.1 microM) (124%). In conclusion, the effects of 5
      HT(4) receptor agonists on proximal stomach motor activity in vivo can be
      explained by an effect on 5-HT(4) receptors on cholinergic nerves within the
      gastric muscle wall.

PMID- 11309268
TI  - Long-lasting antinociceptive effects of a novel dynorphin analogue, Tyr-D-Ala-Phe
      Leu-Arg psi (CH(2)NH) Arg-NH(2), in mice.
AB  - Tyr-D-Ala-Phe-Leu-Arg psi (CH(2)NH) Arg-NH(2) (SK-9709) is a dynorphin derivative
      in which the peptide bond was replaced with a psi (CH(2)NH) bond. In the present
      study, the antinociceptive effects of SK-9709 were determined in an acetic acid
      induced writhing test and a hot-plate test. In the acetic acid-induced writhing
      test, significant antinociceptive effects were observed after subcutaneous
      (s.c.), intracerebroventricular (i.c.v.) and intrathecal (i.t.) injection of SK
      9709, with maximal effects at 120, 30 and 15 min, respectively. The
      antinociceptive effects were dose-dependent and ED(50) values (range of 95%
      confidence limits) after s.c., i.c.v. and i.t. injection were 1.36 (0.61 - 3.02)
      micromol kg(-1), 2.11 (1.18 - 3.79) and 0.79 (0.61 - 1.03) nmol per mouse,
      respectively. The effects of SK-9709 (s.c., i.c.v. and i.t.) were reversed by the
      opioid receptor antagonist naloxone (1.36 micromol kg(-1), s.c.). The effects of
      SK-9709 (s.c.) were also reversed by the selective mu-opioid receptor antagonist
      beta-funaltrexamine (4.7 nmol per mouse, i.c.v.), and kappa-opioid receptor
      antagonist nor-binaltorphimine (4.9 nmol per mouse, i.t.). In the hot-plate test,
      the antinociceptive effect of SK-9709 (s.c., i.c.v. and i.t.) was also dose
      dependent with the maximal peak effect at 120, 15 and 15 min similarly to the
      acetic acid-induced writhing test. The antinociceptive effects were dose
      dependent and ED(50) values (range of 95% confidence limits) after s.c., i.c.v.
      and i.t. injection were 39.1 (5.4 - 283.0) micromol kg(-1), 6.5 (4.0 - 10.7) and
      7.4 (5.0 - 11.0) nmol per mouse, respectively. These findings indicated that
      systemically administered SK-9709 produced long-lasting antinociceptive effects
      and these effects were mediated by both supra-spinal mu- and spinal kappa-opioid
      receptors.

PMID- 11309269
TI  - Rat arterial smooth muscle devoid of ryanodine receptor function: effects on
      cellular Ca(2+) handling.
AB  - The roles of intracellular Ca(2+) stores and ryanodine (Ry) receptors for
      vascular Ca(2+) homeostasis and viability were investigated in rat tail arterial
      segments kept in organ culture with Ry (10 - 100 microM) for up to 4 days. Acute
      exposure to Ry or the non-deactivating ryanodine analogue C(10)-O(eq) glycyl
      ryanodine (10 microM) eliminated Ca(2+) release responses to caffeine (20 mM) and
      noradrenaline (NA, 10 microM), whereas responses to NA, but not caffeine,
      gradually returned to normal within 4 days of exposure to RY: Ry receptor protein
      was detected on Western blots in arteries cultured either with or without RY:
      Brief Ca(2+) release events (sparks) were absent after culture with Ry, whereas
      Ca(2+) waves still occurred. The propagation velocity of waves was equal (
      approximately 19 microm s(-1)) in tissue cultured either with or without RY:
      Inhibition of Ca(2+) accumulation into the sarcoplasmic reticulum (SR) by culture
      with caffeine (5 mM), cyclopiazonic acid or thapsigargin (both 10 microM)
      decreased contractility due to Ca(2+)-induced cell damage. In contrast, culture
      with Ry did not affect contractility. Removal of Ca(2+) from the cytosol
      following a Ca(2+) load was retarded after Ry culture. Thapsigargin reduced the
      rate of Ca(2+) removal in control cultured rings, but had no effect after Ry
      culture. It is concluded that intracellular Ca(2+) stores recover during chronic
      Ry treatment, while Ry receptors remain non-functional. Ry receptor activity is
      required for Ca(2+) sparks and for SR-dependent recovery from a Ca(2+) load, but
      not for Ca(2+) waves or basal Ca(2+) homeostasis.

PMID- 11309270
TI  - A gene hypermethylation profile of human cancer.
AB  - We are in an era where the potential exists for deriving comprehensive profiles
      of DNA alterations characterizing each form of human cancer. Such profiles would
      provide invaluable insight into mechanisms underlying the evolution of each tumor
      type and will provide molecular markers, which could radically improve cancer
      detection. To date, no one type of DNA change has been defined which accomplishes
      this purpose. Herein, by using a candidate gene approach, we show that one
      category of DNA alteration, aberrant methylation of gene promoter regions, can
      enormously contribute to the above goals. We have now analyzed a series of
      promoter hypermethylation changes in 12 genes (p16(INK4a), p15(INK4b), p14(ARF),
      p73, APC,(5) BRCA1, hMLH1, GSTP1, MGMT, CDH1, TIMP3, and DAPK), each rigorously
      characterized for association with abnormal gene silencing in cancer, in DNA from
      over 600 primary tumor samples representing 15 major tumor types. The genes play
      known important roles in processes encompassing tumor suppression, cell cycle
      regulation, apoptosis, DNA repair, and metastastic potential. A unique profile of
      promoter hypermethylation exists for each human cancer in which some gene changes
      are shared and others are cancer-type specific. The hypermethylation of the genes
      occurs independently to the extent that a panel of three to four markers defines
      an abnormality in 70-90% of each cancer type. Our results provide an unusual view
      of the pervasiveness of DNA alterations, in this case an epigenetic change, in
      human cancer and a powerful set of markers to outline the disruption of critical
      pathways in tumorigenesis and for derivation of sensitive molecular detection
      strategies for virtually every human tumor type.

PMID- 11309271
TI  - A mutator phenotype in cancer.
AB  - We have proposed that an early step in tumor progression is the expression of a
      mutator phenotype resulting from mutations in genes that normally function in the
      maintenance of genetic stability. There is new and strong experimental evidence
      that supports the concept of a mutator phenotype in cancer. As technologies for
      chromosomal visualization and DNA advance, there are increasing data that human
      cancer cells contain large numbers of mutations. First, I will review the concept
      of a mutator phenotype. Second, I will present the recent evidence that
      individual cancer cells contain thousands of mutations. Third, I will explore
      potential target genes that are required for maintenance of genetic stability in
      normal cells and ask if they are mutated in cancer cells. Fourth, I will address
      the timing of a mutator phenotype; is it an early event during tumor progression?
      Do tumors already contain cells that harbor mutations rendering them resistant to
      most chemotherapeutic agents? Lastly, I will speculate on the theoretical and
      practical implication of a mutator phenotype in cancer and consider the
      possibility of cancer prevention by delay, i.e., a reduction in mutation rates
      early during carcinogenesis might slow the progression of tumors.

PMID- 11309272
TI  - Tumor cells regulate the lytic activity of tumor-specific cytotoxic t lymphocytes
      by modulating the inhibitory natural killer receptor function.
AB  - Tumor-infiltrating p58+ T cells from a renal tumor were specifically expanded in
      response to tumor cell stimulation and cloned. These p58+ T cells were found to
      express a memory phenotype and corresponded to clonal TCRBV3 T-cell expansion.
      Functionally, p58(+) CTLs displayed a low lytic activity for HLA-A2 tumor and
      normal cells. However, this lytic activity was significantly increased after
      blockade of p58 with specific monoclonal antibodies. Interestingly, we
      demonstrated that stimulation by tumor cells was required to trigger the
      inhibitory effect of p58 on the lytic activity of antigen-specific CTLs and that
      stimulation of the inhibitory function of p58 by tumor cells correlated with an
      inhibition of nuclear factor-kappaB activation in p58+ tumor-specific CTLS.

PMID- 11309273
TI  - Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin.
AB  - Inappropriate activation of the Wnt/beta-catenin signaling, resulting mainly from
      activating mutations of the beta-catenin gene, has been implicated recently in
      the development of hepatocellular carcinoma (HCC). We have generated transgenic
      mice expressing an oncogenic form of beta-catenin in their hepatocytes to analyze
      the effect of deregulated beta-catenin signaling on liver homeostasis. These mice
      rapidly developed hepatomegaly soon after birth, with livers three to four times
      heavier than those of nontransgenic littermates. The liver cell hyperplasia
      resulted from increased cell proliferation without any compensatory apoptosis.
      Although the genes encoding c-myc and cyclin D1 are potential targets of the beta
      catenin signaling pathway, neither of them was overexpressed in the hyperplastic
      livers of beta-catenin transgenic mice. Thus, the key target genes of the beta
      catenin signaling pathway in the liver remain to be identified.

PMID- 11309274
TI  - Molecular regulation of tumor cell vasculogenic mimicry by tyrosine
      phosphorylation: role of epithelial cell kinase (Eck/EphA2).
AB  - During embryogenesis, blood vessels are formed initially by the process of
      vasculogenesis, the in situ differentiation of mesenchymal cells into endothelial
      cells, which form a primitive, patterned vasculogenic network. This is followed
      by angiogenesis, the sprouting of new vessels from preexisting vasculature, to
      yield a more refined microcirculation. However, we and our collaborators have
      recently described a process termed "vasculogenic mimicry," which consists of the
      formation of patterned, tubular networks by aggressive melanoma tumor cells (in
      three-dimensional cultures in vitro), that mimics endothelial-formed vasculogenic
      networks and correlates with poor clinical prognosis in patients. Previous
      microarray analysis from our laboratory comparing the highly aggressive versus
      the poorly aggressive melanoma cells revealed a significant increased expression
      of tyrosine kinases associated with the aggressive melanoma phenotype. Because of
      the important role of protein tyrosine kinases in phosphorylating various signal
      transduction proteins that are critical for many cellular processes (e.g., cell
      adhesion, migration, and invasion), we examined whether protein tyrosine kinases
      are involved in melanoma vasculogenic mimicry. Immunofluorescence analysis of
      aggressive melanoma cells forming tubular networks in vitro showed that tyrosine
      phosphorylation activity colocalized specifically within areas of tubular network
      formation. A phosphotyrosine profile of the aggressive melanoma cells capable of
      forming tubular networks indicated differences in tyrosine phosphorylated
      proteins compared with the poorly aggressive melanoma cells (incapable of forming
      tubular networks). Most notably, we identified epithelial cell kinase (EphA2) as
      being one receptor tyrosine kinase expressed and phosphorylated exclusively in
      the aggressive metastatic melanoma cells. Furthermore, general inhibitors of
      protein tyrosine kinases hindered tube formation, and transient knockout of EphA2
      abrogated the ability of tumor cells to form tubular structures. These results
      suggest that protein tyrosine kinases, particularly EphA2, are involved in the
      formation of tubular networks by aggressive melanoma tumor cells in vitro, which
      may represent a novel therapeutic target for further clinical investigation.

PMID- 11309275
TI  - Alternative pathways to prostate carcinoma activate prostate stem cell antigen
      expression.
AB  - Prostate Stem Cell Antigen (PSCA) is a glycosylphosphatidylinositol-anchored cell
      surface protein that is expressed in normal human prostate and overexpressed in
      human prostate cancers. To test whether different pathways that generate prostate
      cancer would affect PSCA expression, a murine model system was developed.
      Monoclonal antibodies were generated against murine PSCA (mPSCA). mPSCA is
      expressed on approximately 20% of cells in normal prostate epithelium, and this
      number decreases with increasing age. In the transgenic adenocarcinoma of the
      mouse prostate (TRAMP) model of prostate cancer, tumors develop between 19 and 25
      weeks of age. Murine PSCA was strongly expressed on approximately 60% of the
      cells of TRAMP tumors, at an age where the number of PSCA+ cells and the level of
      expression of PSCA is very low in the normal prostate. Phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) +/- mice develop a number of different
      cancers, including prostate cancer. The incidence of prostate cancer is low and
      occurs after a relatively long latency. Fluorescence-activated cell sorter
      analysis of prostatic tissue from 11-18-month-old PTEN +/- mice showed elevated
      numbers of PSCA+ cells in the prostate, and immunohistochemical analysis showed
      high mPSCA expression in the tumors of these mice. Together, these results show
      that two distinct mechanisms of carcinogenesis lead to expression of a common
      target antigen.

PMID- 11309276
TI  - Cytosine-phosphoguanine methylation of estrogen receptors in endometrial cancer.
AB  - We hypothesize that estrogen receptors (ERs) are differentially expressed in
      endometrial cancer. To test this hypothesis, we investigated the expression
      profile of ERalpha (ERalpha-A, ERalpha-B, ERalpha-C) and ERbeta genes and CpG
      methylation status in endometrial cancer cell lines and tissues using reverse
      transcription-PCR and methylation-specific PCR and direct DNA sequencing. The
      results demonstrated that ERalpha-A, ERalpha-B, and ERbeta were normally
      expressed whereas ERalpha-C gene was inactivated in all endometrial cancer cell
      lines. We further investigated the mechanisms of ERalpha-C gene inactivation
      through CpG methylation pathways. The treatment with demethylating agent (5'-aza
      2'-deoxycytidine) restored ERalpha-C gene expression in all endometrial cancer
      cell lines. We further confirmed these findings with methylation-specific PCR and
      direct DNA sequencing and found that only ERalpha-C was methylated on all five
      different CpG sites in all cell lines. We further analyzed 88 cancerous and 46
      normal endometrial tissues. The results demonstrated that only ERalpha-C was
      inactivated and methylated in 94% of cancer tissues. In 32 pairs of cancerous and
      normal endometrial tissues from the same patient, ERalpha-C was methylated in 29
      of 32 cancer tissues but unmethylated in all normal endometrial tissues. This is
      the first report that demonstrates selective ERalpha-C gene inactivation through
      CpG methylation pathway in uterine endometrial cancer.

PMID- 11309277
TI  - Promotion of seminomatous tumors by targeted overexpression of glial cell line
      derived neurotrophic factor in mouse testis.
AB  - We show with transgenic mice that targeted overexpression of glial cell line
      derived neurotrophic factor (GDNF) in undifferentiated spermatogonia promotes
      malignant testicular tumors, which express germ-cell markers. The tumors are
      invasive and contain aneuploid cells, but no distant metastases have been found.
      By several histological, molecular, and histochemical characteristics, the GDNF
      induced tumors mimic classic seminomas in men, representing a useful experimental
      model for testicular germ-cell tumors. The data also show that a deregulated
      stimulation of a normal proto-oncogene by its ligand can be an initiative event
      in carcinogenesis.

PMID- 11309278
TI  - Methylenetetrahydrofolate reductase polymorphisms increase risk of esophageal
      squamous cell carcinoma in a Chinese population.
AB  - Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate
      metabolism that affects DNA methylation and synthesis. Because germ-line
      mutations at nucleotides 677 (C-->T) and 1298 (A-->C) in the MTHFR gene cause
      diminished enzyme activity, and aberrant DNA methylation is oncogenic, we
      examined the relationship between these two MTHFR polymorphisms and
      susceptibility to esophageal squamous cell carcinoma (ESCC) in 240 ESCC cases and
      360 age- and sex-matched controls in northern CHINA: We found that the allele
      frequency of MTHFR 677T was significantly higher among cases than among controls
      (63% versus 41%, P < 0.001). Subjects with the 677TT genotype had a more than 6
      fold increased risk of developing ESCC [adjusted odds ratio (OR), 6.18; 95%
      confidence interval (CI), 3.32-11.51] compared with those who had the 677CC
      genotype. Furthermore, the elevated ESCC risk associated with the 677
      polymorphism was in an allele-dose relationship (trend test, P = 0.0001) with ORs
      of 1.00, 3.14 (95% CI, 1.94-5.08), and 6.18 (95% CI, 3.32-11.51) for the CC, CT,
      and TT genotype, respectively, after adjustment for age, sex, smoking status, and
      the MTHFR 1298 polymorphism. The allele frequency for the MTHFR 1298C was 14%
      among cases and 17% among controls. The 1298CC genotype was extremely rare in
      both controls (1.4%) and cases (2.9%) and was also associated with an elevated
      risk of ESCC (adjusted OR, 4.43; 95% CI, 1.23-16.02) compared with the 1298AA
      genotype, whereas the 1298AC genotype had no effect on the risk of ESCC. Thus,
      our findings support the hypothesis that genetic polymorphisms in the MTHFR gene
      may contribute to susceptibility to carcinogenesis of the esophagus in the at
      risk Chinese population.

PMID- 11309279
TI  - Overexpression of a dominant-negative signal transducer and activator of
      transcription 3 variant in tumor cells leads to production of soluble factors
      that induce apoptosis and cell cycle arrest.
AB  - Gene therapy of B16 tumors with a dominant-negative signal transducer and
      activator of transcription (Stat3) variant, designated Stat3beta, results in
      inhibition of tumor growth and tumor regression. Although only 10-15% of the
      tumor cells are transfected in vivo, the Stat3beta-induced antitumor effect is
      associated with massive apoptosis of B16 tumor cells, indicative of a potent
      bystander effect. Here, we provide evidence that blocking Stat3 signaling in B16
      cells results in release of soluble factors that are capable of inducing
      apoptosis and cell cycle arrest of nontransfected B16 cells. RNase protection
      assays using multi-template probes specific for key physiological regulators of
      apoptosis reveal that overexpression of Stat3beta in B16 tumor cells induces the
      expression of the apoptotic effector, tumor necrosis factor-related apoptosis
      inducing ligand. These in vitro results suggest that the observed in vivo
      bystander effect leading to tumor cell growth inhibition is mediated, at least in
      part, by soluble factors produced as a result of overexpression of Stat3beta in
      tumor cells.

PMID- 11309280
TI  - Effective tumor therapy with plasmid-encoded cytokines combined with in vivo
      electroporation.
AB  - Plasmids may have unique advantages as a gene delivery system. However, a major
      obstacle is the low in vivo transduction efficiency. In this study, an
      electroporation-based gene transduction approach was taken to study the effect of
      interleukin (IL)-2 or IL-12 gene transduction on the growth of experimental
      murine tumors. Significant intratumoral gene transduction was achieved by
      electroporation of tumors that had been injected with naked plasmids encoding
      reporter genes and cytokine genes (IL-2 and IL-12) under the control of a
      constitutive cytomegalovirus promoter. In addition, significant tumor growth
      delay could be achieved in a murine melanoma line B16.F10 with the cytokine
      genes. Most importantly, systemic transgene levels were negligible when compared
      with intratumoral adenovirus-mediated IL-12 gene delivery, which leads to
      significantly higher systemic cytokine levels. Therefore, naked plasmid- and in
      vivo electroporation-mediated cancer gene therapy may be therapeutically
      efficacious while maintaining low systemic toxicity.

PMID- 11309281
TI  - Nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) alter the
      kinetics of human colon cancer cell lines more effectively than traditional
      NSAIDs: implications for colon cancer chemoprevention.
AB  - Nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs),
      consisting of a known nonsteroidal anti-inflammatory drug (NSAID) and a nitric
      oxide (NO)-releasing group, are reported safer than NSAIDS: To assess their
      potential in colon cancer chemoprevention, we studied in vitro the effect of NO
      aspirin, NO-sulindac, and NO-ibuprofen on colonocyte kinetics. These three NO
      NSAIDs reduced the growth of cultured HT-29 colon adenocarcinoma cells much more
      effectively than the corresponding NSAIDs; e.g., at 24 h, their IC(50) values
      were as follows: (a) aspirin, >5000 microM; (b) NO-aspirin, 1 microM; (c)
      sulindac, 750 microM; (d) NO-sulindac, 150 microM; (e) ibuprofen, >1000 microM;
      and (f) NO-ibuprofen, 42 microM. This effect was due to inhibition of
      proliferation and induction of apoptosis and perhaps to the induction of novel
      cell changes, characterized by extensive DNA degradation. NO-NSAIDs also blocked
      the G(0)-G(1) to S cell cycle transition. Their superior effectiveness compared
      with traditional NSAIDs, combined with their reported safety, makes them
      promising candidates for chemopreventive agents against colon cancer.

PMID- 11309282
TI  - Angiogenic activity of pyruvic acid in in vivo and in vitro angiogenesis models.
AB  - The excessive growth of a tumor requires high rates of glucose uptake and
      glycolysis and continuous recruitment of new blood vessels. Here, we provide
      several lines of evidence showing that pyruvic acid, the end product of
      glycolysis, exhibits strong angiogenic activity. Pyruvic acid promoted
      angiogenesis in chorioallantoic membrane assay and in vivo mouse Matrigel plug
      assay. Pyruvic acid also positively affects angiogenic cascade, DNA synthesis,
      migration, and tube formation in bovine aortic endothelial cells. Furthermore,
      mRNA expression of fibroblast growth factor receptor-2 and vascular endothelial
      growth factor was enhanced by pyruvic acid. These results strongly suggest that
      pyruvic acid plays an important role in angiogenesis for tumor growth and
      metastasis.

PMID- 11309283
TI  - Neutral endopeptidase inhibits neuropeptide-mediated transactivation of the
      insulin-like growth factor receptor-Akt cell survival pathway.
AB  - G-protein coupled receptor (GPCR) agonists such as neuropeptides activate the
      insulin-like growth factor-1 receptor (IGF-IR) or the serine-threonine protein
      kinase Akt, suggesting that neuropeptides-GPCR signaling can cross-communicate
      with IGF-IR-Akt signaling pathways. Neutral endopeptidase 24.11 (NEP) is a cell
      surface peptidase that cleaves and inactivates the neuropeptides endothelin-1 (ET
      1) and bombesin, which are implicated in progression to androgen-independent
      prostate cancer (PC). We investigated the mechanisms of NEP regulation of
      neuropeptide-mediated cell survival in PC cells, including whether neuropeptide
      substrates of NEP induce phosphorylations of IGF-IR and Akt in PC cells. Western
      analyses revealed ET-1 and bombesin treatment induced phosphorylation of IGF
      IRbeta and Akt independent of IGF-I in TSU-Pr1, DU145, and PC-3 PC cells, which
      lack NEP expression, but not in NEP-expressing LNCaP cells. Recombinant NEP and
      induced NEP expression in TSU-Pr1 cells using a tetracycline-repressive
      expression system inhibited ET-1-mediated phosphorylation of IGF-IRbeta and Akt,
      and blocked the protective effects of ET-1 against apoptosis induced by serum
      starvation. Incubation of TSU-Pr1 cells with specific kinase inhibitors together
      with ET-1 or bombesin showed that IGF-IR activation is required for neuropeptide
      induced Akt phosphorylation, and that neuropeptide-induced Akt activation is
      predominantly mediated by Src and phosphatidylinositol 3-kinase but not by
      mitogen-activated protein kinase or protein kinase C. These data show that the
      neuropeptides ET-1 and bombesin stimulate ligand-independent activation of the
      IGF-IR, which results in Akt activation, and that this cross-communication
      between GPCR and IGF-IR signaling is inhibited by NEP.

PMID- 11309284
TI  - The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45
      related factor 2) controls both constitutive and inducible expression of
      intestinal detoxification and glutathione biosynthetic enzymes.
AB  - Northern blotting has shown that mouse small intestine contains relatively large
      amounts of the nuclear factor-E2 p45-related factor (Nrf) 2 transcription factor
      but relatively little Nrf1. Regulation of intestinal antioxidant and detoxication
      enzymes by Nrf2 has been assessed using a mouse line bearing a targeted
      disruption of the gene encoding this factor. Both Nrf2-/- and Nrf2+/+ mice were
      fed a control diet or one supplemented with either synthetic cancer
      chemopreventive agents [butylated hydroxyanisole (BHA), ethoxyquin (EQ), or
      oltipraz] or phytochemicals [indole-3-carbinol, cafestol and kahweol palmitate,
      sulforaphane, coumarin (CMRN), or alpha-angelicalactone]. The constitutive level
      of NAD(P)H:quinone oxidoreductase (NQO) and glutathione S-transferase (GST)
      enzyme activities in cytosols from small intestine was typically found to be
      between 30% and 70% lower in samples prepared from Nrf2 mutant mice fed a control
      diet than in equivalent samples from Nrf2+/+ mice. Most of the chemopreventive
      agents included in this study induced NQO and GST enzyme activities in the small
      intestine of Nrf2+/+ mice. Increases of between 2.7- and 6.2-fold were observed
      in wild-type animals fed diets supplemented with BHA or EQ; increases of about 2
      fold were observed with a mixture of cafestol and kahweol palmitate, CMRN, or
      alpha-angelicalactone; and increases of 1.5-fold were measured with sulforaphane.
      Immunoblotting confirmed that in the small intestine, the constitutive level of
      NQO1 is lower in the Nrf2-/- mouse, and it also showed that induction of the
      oxidoreductase was substantially diminished in the mutant mouse. Immunoblotting
      class-alpha and class-mu GST showed that constitutive expression of most
      transferase subunits is also reduced in the small intestine of Nrf2 mutant mice.
      Significantly, induction of class-alpha and class-mu GST by EQ, BHA, or CMRN is
      apparent in the gene knockout animal. No consistent change in the constitutive
      levels of the catalytic heavy subunit of gamma-glutamylcysteinyl synthetase
      (GCS(h)) was observed in the small intestine of Nrf2-/- mice. However, although
      the expression of GCS(h) was found to be increased dramatically in the small
      intestine of Nrf2+/+ mice by dietary BHA or EQ, this induction was essentially
      abolished in the knockout mice. It is apparent that Nrf2 influences both
      constitutive and inducible expression of intestinal antioxidant and detoxication
      proteins in a gene-specific fashion. Immunohistochemistry revealed that induction
      of NQO1, class-alpha GST, and GCS(h) occurs primarily in epithelial cells of the
      small intestine. This suggests that the variation in inducibility of NQO1,
      Gsta1/2, and GCS(h) in the mutant mouse is not attributable to the expression of
      the enzymes in distinct cell types but rather to differences in the dependency of
      these genes on Nrf2 for induction.

PMID- 11309285
TI  - Synthetic peptides inhibit adhesion of human tumor cells to extracellular matrix
      proteins.
AB  - Human tumor cell progression and metastasis are partially dependent on the
      ability of a tumor cell to adhere to the proteins of the extracellular matrix
      (ECM) and survive at the distant location. Six novel D-amino acid-containing
      peptides were analyzed for their ability to adhere to human prostate tumor cells,
      support tumor cell adhesion, and inhibit tumor cell adhesion to ECM proteins or
      human dermal fibroblasts. Of these, two peptides called RZ-3 (kmviywkag) and HYD
      1 (kikmviswkg) bound to tumor cell surfaces and compared favorably with the
      previously reported AG-73 (RKRLQVQLSIRT) L-amino acid peptide, as determined by
      fluorescence-activated cell sorting analysis. A scrambled peptide derivative of
      HYD-1, called HYDS-1 (wiksmkivkg), was not active. The RZ-3, HYD-1, and AG-73
      peptides supported maximal cancer cell adhesion at 5 microg, 10 microg, and 50
      microg/well, respectively. The ECM proteins fibronectin, laminin 1, and collagen
      IV supported maximal cell adhesion at 1 microg, >10 microg, and 50 microg/well,
      respectively. Prostate tumor cell adhesion to immobilized RZ-3 and HYD-1 peptides
      was inhibited by alpha2-6- and beta1-integrin-blocking antibodies. Conversely,
      tumor cell adhesion to a beta1-integrin-specific antibody was blocked by both RZ
      3 and HYD-1. Epithelial cell adhesion to dermal fibroblasts was inhibited by HYD
      1 and unaffected by the scrambled peptide, HYDS-1. Cell adhesion to immobilized
      peptides was unaffected by EDTA. The soluble RZ-3 and HYD-1 peptides inhibited
      tumor cell adhesion to each of the immobilized four ECM proteins (1.0
      microg/well) in a time- and concentration-dependent manner. The IC(50) of the RZ
      3 peptide for blocking adhesion to fibronectin, laminin 1, laminin 5, and
      collagen IV was 2.4 microg, 1.8 microg, 4.6 microg, and 2.8 microg/well,
      respectively. The IC(50) of the HYD-1 peptide for blocking adhesion to
      fibronectin, laminin 1, laminin 5, and collagen IV was 6.9 microg, 5.7 microg,
      >10 microg, and 6.2 microg/well, respectively. Taken together, these results
      indicate that RZ-3 and HYD-1 are biologically active D-amino acid-containing
      peptides that can themselves support tumor cell adhesion and can inhibit tumor
      cell adhesion to immobilized ECM proteins or dermal fibroblasts.

PMID- 11309286
TI  - Prevention of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the MCF
      10A cell line: correlation with increased transforming growth factor alpha
      production.
AB  - We have recently reported that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      inhibits epidermal growth factor (EGF) withdrawal-induced apoptosis in the human
      mammary epithelial cell line MCF-10A. We hypothesized that TCDD-mediated
      inhibition of apoptosis was due to its ability to stimulate the EGF receptor
      (EGFR) pathway. Indeed, in the present studies, the EGFR inhibitor AG1478 was
      able to prevent TCDD-, EGF-, and transforming growth factor alpha (TGF-alpha)
      dependent cell recovery and inhibition of apoptosis. These effects were specific
      for an EGFR-mediated pathway because cotreatment with AG825, an erbB2 inhibitor,
      had little effect on apoptosis. In addition, TCDD was able to mimic the EGF and
      TGF-alpha signaling as demonstrated by increasing Akt and extracellular signal
      regulated kinase 1,2 phosphorylation. These effects were dependent on EGFR
      activity because AG1478, but not AG825, was able to prevent EGF-, TGF-alpha, or
      TCDD-mediated Akt and extracellular signal-regulated kinase 1,2 phosphorylation.
      The ability of TCDD to stimulate the EGFR pathway and inhibit apoptosis may be
      due to the ability of TCDD to increase expression of TGF-alpha, a ligand for
      EGFR. Treatment with 10 nM TCDD increased TGF-alpha mRNA at 2 h and TGF-alpha
      protein at 6 h. These data suggest a mechanism whereby TCDD is able to inhibit
      apoptosis in human mammary epithelial cells by stimulating TGF-alpha production,
      resulting in an autocrine effect.

PMID- 11309287
TI  - An intronic poly (AT) polymorphism of the DNA repair gene XPC and risk of
      squamous cell carcinoma of the head and neck: a case-control study.
AB  - Inherited polymorphisms of DNA repair genes may contribute to variations in DNA
      repair capacity and genetic susceptibility to cancer. In a hospital-based case
      control study of 287 non-Hispanic white patients with newly diagnosed SCCHN and
      311 control subjects matched on age, sex, ethnicity, and smoking status, we
      investigated the role of a newly identified variant allele of XPC, XPC-PAT+. We
      found that the frequency of the XPC-PAT+ allele was higher in the cases (0.409)
      than in the controls (0.333; P = 0.007). Fifty cases (17.4%) and 37 controls
      (11.9%) were XPC-PAT+/+, and 135 (47.0%) cases and 133 controls (42.8%) were XPC
      PAT+/-. XPC-PAT+/- and XPC-PAT+/+ subjects were at significantly increased risk
      for SCCHN [adjusted odds ratios = 1.44 and 1.85, respectively (95% confidence
      intervals, 1.01-2.05 and 1.12-3.05, respectively; trend test, P = 0.007)]. We did
      not find ethnic difference in the frequency of XPC-PAT+ allele among four groups
      aged between 19 and 75 years: non-Hispanic whites, 294; African-Americans, 178;
      Hispanic-Americans, 103; and native Chinese, 119 (0.333, 0.281, 0.296, and 0.353,
      respectively). The case-control findings support the hypothesis that the XPC-PAT+
      allele may contribute to the risk of developing SCCHN.

PMID- 11309288
TI  - Do urinary estrogen metabolites reflect the differences in breast cancer risk
      between Singapore Chinese and United States African-American and white women?
AB  - Breast cancer risk is substantially lower in Singapore than in women from the
      United STATES: Part of the risk discrepancy is probably explained by differences
      in the production of endogenous estrogens, but differences in the pathway by
      which estrogen is metabolized may also play a role. We undertook a study to
      determine whether the ratio of urinary 2-hydroxyestrone (2OHE(1)):16alpha
      hydroxyestrone (16alpha-OHE(1)) was higher in Singapore Chinese than in a group
      of United States (predominantly African-American) women living in Los ANGELES: We
      also wanted to determine whether any difference in estrogen metabolite ratio
      between these two groups of women was greater than that in estrone (E(1)),
      estradiol (E(2)) and estriol (E(3)). The participants in this study were randomly
      selected healthy, non-estrogen using women participating in the Singapore Chinese
      Health Study (n = 67) or the Hawaii/Los Angeles Multiethnic Cohort Study (n =
      58). After adjusting for age and age at menopause, mean urinary 2-OHE(1) was only
      23% (P = 0.03) higher in Singapore Chinese than in United States women, and there
      were no statistically significant differences in 16alpha-OHE(1) levels or in the
      ratio of 2-OHE(1):16alpha-OHE(1) between the two groups. The adjusted mean 2
      OHE(1):16alpha-OHE(1) ratio was 1.63 in Singapore Chinese and 1.48 in United
      States women (P = 0.41). In contrast, the adjusted mean values of E1, E2, and E3
      were 162% (P < 0.0001), 152% (P < 0.0001), and 92% (P = 0.0009) higher,
      respectively, in United States women than in Singapore Chinese women. Our study
      suggests that urinary E1, E2, and E3 reflect the differences in breast cancer
      risk between Singapore Chinese and United States women to a stronger degree than
      the estrogen metabolites 2OHE(1) and 16alpha-OHE(1) or the ratio of
      2OHE(1):16alpha-OHE(1.)

PMID- 11309289
TI  - Antitumor activity and bystander effects of the tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) gene.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported
      to specifically kill malignant cells but to be relatively nontoxic to normal
      cells. To evaluate the antitumor activity and therapeutic value of the TRAIL
      gene, we constructed adenoviral vectors expressing the human TRAIL gene and
      transferred them into malignant cells in vitro and tumors in vivo. The in vitro
      transfer elicited apoptosis, as demonstrated by the quantification of viable or
      apoptotic cells and by the analysis of activation of pro-caspase-8 and cleavage
      of poly(ADP-ribose) polymerase. The intratumoral delivery elicited tumor cell
      apoptosis and suppressed tumor growth. In comparison with Bax gene treatment,
      which is toxic to normal cells, TRAIL gene treatment caused no detectable
      toxicity in cultured normal fibroblasts nor in mouse hepatocytes after systemic
      gene delivery. Furthermore, coculture of cancer cells expressing TRAIL with those
      expressing green fluorescent protein (GFP) resulted in apoptosis of both cells,
      whereas coculture of Bax-expressing cells with GFP-expressing cells resulted in
      the cell death of the Bax-expressing cells only, which suggested that the
      transfer of the TRAIL gene resulted in bystander effects. Moreover, culture of
      cells with medium from TRAIL-expressing cells showed the proapoptotic activity
      and bystander effect of the TRAIL gene to be not transferable with medium. To
      further demonstrate the bystander effect of the TRAIL gene, we constructed
      plasmid vectors encoding GFP-TRAIL or GFP-Bik chimeric proteins. Transfection of
      the GFP-TRAIL gene into cancer cells resulted in the death of GFP-positive cells
      and their neighbors, whereas transfection of the GFP-Bik gene killed GFP-positive
      cells only. Finally, GFP-TRAIL genes, transfected into normal human fibroblasts
      or bronchial epithelial cells, did not kill such cells, whereas transfected GFP
      Bik genes did. Thus, the direct transfer of the TRAIL gene led to selective
      killing of malignant cells with bystander effect, which suggests that the TRAIL
      gene could be valuable for treatment for cancers. Together, these results suggest
      that delivering the TRAIL gene to cancerous cells may be an alternative approach
      to cancer treatment.

PMID- 11309290
TI  - Cloning and characterization of human adenosine 5'-triphosphate-binding cassette,
      sub-family A, transporter 2 (ABCA2).
AB  - We have isolated the full-length cDNA for human ATP-binding cassette, sub-family
      A, member 2 transporter (ABCA2). The ORF of this cDNA encodes a protein
      consisting of 2436 amino acids with apparent molecular weight of M(r) 270,000.
      Accordingly, ABCA2 is the largest known mammalian ABC transporter described thus
      far. Analysis of mRNA expression levels indicated that ABCA2 is highest in human
      brain and has a broad expression pattern in a panel of tumor cell lines. Using
      specific antibodies to ABCA2 and various organelle marker proteins, ABCA2 was
      found to colocalize with the lysosomal/endosomal marker LAMP1, forming discrete,
      punctate intracellular vesicles. In ABCA2-transfected cells, the transporter also
      colocalized with a fluorescently labeled steroid analogue, estramustine. The
      sequestration of the steroid into the lysosomal/endosomal compartment indicates a
      potential substrate specificity for ABCA2. Furthermore, the presence of a
      lipocalin signature motif in the ABCA2 sequence suggests a possible broad role
      for this protein in the transport of steroids, lipids, and related molecules.

PMID- 11309291
TI  - Hypoxia in radiation-induced blood-spinal cord barrier breakdown.
AB  - The vascular endothelial cell is believed to be a major target cell of radiation
      induced injury to the central nervous system. Dysfunction of the blood-brain
      barrier is associated with radiation-induced white matter lesions. The aim of
      this study was to determine the role of hypoxia in radiation-induced blood-brain
      barrier disruption. Adult rats were irradiated with graded single doses of 0-22
      Gy to the cervical spinal cord. At various times up to 28 weeks after radiation,
      blood-spinal cord barrier (BSCB) permeability was assessed using
      immunohistochemistry with antialbumin antibody and gamma counting of (99m)Tc
      diethylenetriamine pentaacetic acid. Expression of vascular endothelial growth
      factor (VEGF) was assessed using immunohistochemistry and in situ hybridization.
      Hypoxia was assessed using two 2-nitroimidazole markers, [(125)I]iodoazomycin
      arabinodise and 2-(2-nitro-1H-imidazol-l-yl)-N-(2,2,3,3,3,-pentafluoropropyl)
      acetamide (EF5), with binding in the rat spinal cord measured using gamma
      counting and immunohistochemistry, respectively. In the nonirradiated rat spinal
      cord, there was no evidence of BSCB disruption or VEGF expression. After 16-22
      Gy, there was a dose-dependent increase in albumin staining and (99m)Tc
      diethylenetriamine pentaacetic acid activity beginning at 16 weeks, consistent
      with barrier breakdown. A similar dose-dependent increase in white matter
      astrocytes that showed immunoreactivity and in situ hybridization signals for
      VEGF was observed. No increase in VEGF-positive cells was observed in gray
      matter. By 20 weeks after 20-22 Gy, animals developed white matter necrosis
      associated with diffuse albumin staining. Irradiated rat spinal cord showed a
      dose (16-22 Gy)- and time-dependent (16-20 weeks after 22 Gy) increase in
      [(125)I]iodoazomycin arabinodise accumulation compared to nonirradiated controls.
      A similar pattern of dose- and time-dependent EF5 immunoreactivity was also
      observed in white matter. Areas of EF5 expression and VEGF in situ signals
      colocalized with areas of albumin immunoreactivity. It is concluded that there is
      a dose-dependent temporal and spatial association of hypoxia, VEGF up-regulation,
      and radiation-induced BSCB dysfunction. Hypoxia may provide the signal for VEGF
      up-regulation and perpetuate endothelial permeability damage in the central
      nervous system after ionizing radiation.

PMID- 11309292
TI  - Preemptive control of graft-versus-host disease in a murine allogeneic transplant
      model using retrovirally transduced murine suicidal lymphocytes.
AB  - Suicidal lymphocytes could greatly expand the role of allogeneic transplantation
      by reducing graft-versus-host disease (GVHD) as a barrier to transplantation, but
      optimization of their use is hindered by the lack of adequate animal models. To
      develop an animal model that used retrovirally transduced suicidal lymphocytes in
      a GVHD setting, a well-characterized MHC-matched murine transplant model (B10.BR-
      >AKR/J) was adapted. B10.BR splenic lymphocytes stimulated with concanavalin A
      and interleukin 2 were infected with a retrovirus containing the low-affinity
      nerve growth factor receptor (LNGFR) and the HSV-TK gene and immunomagnetically
      selected; these LNGFR+/TK+ allogeneic lymphocytes were then cotransplanted with 1
      x 10(7) bone marrow cells into lethally irradiated AKR/J recipients. The
      LNGFR+/TK+ donor lymphocytes persisted in the peripheral circulation for 6 months
      in both syngeneic and allogeneic settings. Doses of 2 x 10(6) TK+ allogeneic
      lymphocytes produced GVHD with a severity and time course similar to that induced
      by naive lymphocytes. Survival of TK+ allogeneic lymphocyte-bearing mice was
      significantly improved (P = 0.01) when ganciclovir (GCV; 2 mg/day) was
      administered on days 7-13 post transplant by i.p. injection, demonstrating that
      GVHD could be prevented. Fluorescence-activated cell sorting analysis
      demonstrated 4-fold reduction but persistent circulation of LNGFR+ lymphocytes in
      mice treated with GCV at various time points 1-3 months after transplantation,
      demonstrating selective killing of GVHD-reactive cells. We conclude that
      retrovirally transduced LNGFR+/TK+ murine lymphocytes can be produced, persist
      after transplant, remain alloreactive, and can be killed by GCV administration,
      resulting in reduced GVHD.

PMID- 11309293
TI  - 24-Oxo metabolites of vitamin D3 analogues: disassociation of their prominent
      antileukemic effects from their lack of calcium modulation.
AB  - The seco-steroid hormone, 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]
      inhibits proliferation and induces differentiation of malignant cells including
      those of the hematopoietic system. The 24-oxo metabolite of 1,25(OH)(2)D(3) also
      has prominent antiproliferative activities against various cancer cells. We
      chemically synthesized five novel 24-oxo vitamin D(3) analogues and evaluated
      their abilities both to inhibit clonal growth and induce differentiation of
      myeloid leukemia cells and to cause hypercalcemia. The 1alpha,25-dihydroxy-16-ene
      D(3) [1,25(OH)(2)-16-ene-D(3)] and 1alpha,25-dihydroxy-16-ene-19-nor-D(3)
      [1,25(OH)(2)-16-ene-19-nor-D(3)] and their 24-oxo metabolites showed greater
      potency than 1,25(OH)(2)D(3) in their abilities to inhibit clonal proliferation
      of HL-60, NB4, and U937 leukemic cell lines as measured by methylcellulose soft
      gel assay. Their inhibition of clonal growth was irreversible as analyzed by
      pulse exposure studies. The synthetic analogues also had greater potency than
      1,25(OH)(2)D(3) to induce differentiation of HL-60 and NB4 cells as measured by
      generation of superoxide, nonspecific esterase production, and induction of CD11b
      and CD14 cell surface antigens and to increase the proportion of these cells in
      the G(0)-G(1) phase of the cell cycle. For most assays, the 24-oxo metabolite was
      slightly more potent than the unmodified analogue, and 50% activity was usually
      found in the nanomolar range. These analogues and their 24-oxo metabolites also
      inhibited fresh leukemic cell clonal proliferation. Expression of p27(KIP1), a
      cyclin-dependent kinase inhibitor that plays an important role in blocking the
      cell cycle, was found by Western blot analysis to be induced by the analogues and
      their 24-oxo metabolites in both HL-60 and U937 cells, suggesting a possible
      mechanism by which these analogues inhibit leukemic growth. Notably, the calcemic
      activity tested by injections of 1alpha,25-dihydroxy-16-ene-24-oxo-19-nor-D(3) in
      mice was at least 12-fold less than 1alpha,25(OH)(2)-16-ene-19-nor-D(3). Taken
      together, chemically synthesized 24-oxo metabolites of 1alpha,25(OH)(2)-16-ene
      D(3) and 1alpha,25(OH)(2)-16-ene-19-nor-D(3) irreversibly inhibited proliferation
      and induced differentiation of acute myeloid leukemia cells with minimal
      toxicity; these compounds may have a role in the maintenance phase of therapy for
      acute myeloid leukemia.

PMID- 11309294
TI  - The antiangiogenic property of docetaxel is synergistic with a recombinant
      humanized monoclonal antibody against vascular endothelial growth factor or 2
      methoxyestradiol but antagonized by endothelial growth factors.
AB  - Numerous chemotherapeutic agents have been shown to have an inhibitory effect on
      endothelial cell proliferation and migration, and tubule formation. In this
      study, we examined the antiangiogenic activity of docetaxel. Docetaxel inhibited
      endothelial cell proliferation and tubule formation in vitro in a dose-dependent
      fashion. Docetaxel treatment also inhibited angiogenesis in an in vivo Matrigel
      plug assay. The endothelial stimulating factors, vascular endothelial cell growth
      factor (VEGF) and basic fibroblast growth factor are able to protect endothelial
      cells from the antiangiogenic properties of docetaxel. This protective effect can
      be overcome by a recombinant humanized monoclonal antibody directed against VEGF
      in both in vitro and in vivo models. Similarly, combination of docetaxel with the
      antiangiogenic agent 2-methoxyestradiol also overcomes the protective effect of
      VEGF in both in vitro and in vivo models. These data suggest that
      microenvironmental factors (e.g., local release of VEGF and basic fibroblast
      growth factor) could play a role in decreasing the antiangiogenic effects of
      docetaxel, whereas agents such as 2- methoxyestradiol and recombinant humanized
      monoclonal antibody directed against VEGF may reverse this protective effect.

PMID- 11309295
TI  - p53/p21(CIP1) cooperate in enforcing rapamycin-induced G(1) arrest and determine
      the cellular response to rapamycin.
AB  - The relationship between G(1) checkpoint function and rapamycininduced apoptosis
      was examined using two human rhabdomyosarcoma cell lines, Rh1 and Rh30, that
      express mutated p53 alleles. Serum-starved tumor cells became apoptotic when
      exposed to rapamycin, but were completely protected by expression of a rapamycin
      resistant mutant mTOR. Exposure to rapamycin (100 ng/ml) for 24 h significantly
      increased the proportion of Rh1 and Rh30 cells in G(1) phase, although there were
      no significant changes in expression of cyclins D1, E, or A in drug-treated
      cells. To determine whether apoptosis was associated with continued slow
      progression through G(1) to S phase, cells were exposed to rapamycin for 24 h,
      then labeled with bromodeoxyuridine (BrdUrd). Histochemical analysis showed that
      >90% of cells with morphological signs of apoptosis had incorporated BRDURD: To
      determine whether restoration of G(1) arrest could protect cells from rapamycin
      induced apoptosis, cells were infected with replication-defective adenovirus
      expressing either p53 or p21(CIP1). Infection of Rh30 cells with either Ad-p53 or
      Ad-p21, but not control virus (Ad-beta-gal), induced G(1) accumulation, up
      regulation of p21(CIP1), and complete protection of cells from rapamycin-induced
      apoptosis. Within 24 h of infection of Rh1 cells with Ad-p21, expression of
      cyclin A was reduced by >90%. Similar results were obtained after Ad-p53
      infection of Rh30 cells. Consistent with these data, incorporation of
      [(3)H]thymidine or BrdUrd into DNA was significantly inhibited, as was cyclin
      dependent kinase 2 activity. These data indicate that rapamycin-induced apoptosis
      in tumor cells is a consequence of continued G(1) progression during mTOR
      inhibition and that arresting cells in G(1) phase, by overexpression of p53 or
      p21(CIP1), protects against apoptosis. The response to rapamycin was next
      examined in wild-type or murine embryo fibroblasts nullizygous for p53or
      p21(CIP1). Under serum-free conditions, rapamycin-treated wild-type MEFs showed
      no increase in apoptosis compared to controls. In contrast, rapamycin
      significantly induced apoptosis in cells deficient in p53 ( approximately 2.4
      fold) or p21(CIP1) ( approximately 5.5-fold). Infection of p53(-/-) MEFs with Ad
      p53 or Ad-p21 completely protected against rapamycin-induced apoptosis. Under
      serum-containing conditions, rapamycin inhibited incorporation of BrdUrd
      significantly more in wild-type murine embryo fibroblasts (MEFs) than in those
      lacking p53 or p21(CIP1). When BrdUrd was added 24 h after rapamycin, almost 90%
      and 70% of cells lacking p53 or p21(CIP1), respectively, incorporated nucleoside.
      In contrast, only 19% of wild-type cells incorporated BrdUrd in the presence of
      rapamycin. Western blot analysis of cyclin levels showed that rapamycin had
      little effect on levels of cyclins D1 or E in any MEF strain. However, cyclin A
      was reduced to very low levels by rapamycin in wild-type cells, but remained high
      in cells lacking p53 or p21(CIP1). Taken together, the data suggest that p53
      cooperates in enforcing G(1) cell cycle arrest, leading to a cytostatic response
      to rapamycin. In contrast, in tumor cells, or MEFs, having deficient p53 function
      the response to this agent may be cell cycle progression and apoptosis.

PMID- 11309296
TI  - Attenuation of doxorubicin chronic toxicity in metallothionein-overexpressing
      transgenic mouse heart.
AB  - Previous studies have shown that cardiac-specific metallothionein (MT)
      overexpressing transgenic mice are highly resistant to acute cardiotoxicity
      induced by doxorubicin (DOX), a most effective anticancer agent. However,
      cumulative dose-dependent chronic cardiotoxicity attributable to long-term
      administration of DOX is a significant clinical problem. Because MT is a potent
      antioxidant and oxidative stress is critically involved in DOX-induced heart
      injury, the present study was undertaken to test the hypothesis that MT also
      provides protection against DOX chronic cardiotoxicity. Transgenic mice
      containing high levels of cardiac MT and nontransgenic controls were treated with
      a cumulative dose of 40 mg/kg of DOX in 10 equal i.v. injections over a period of
      7 weeks. Three weeks after the last injection, the mice were killed for an
      analysis of cardiotoxicity. As compared with nontransgenic controls, DOX-induced
      cardiac hypertrophy was significantly inhibited in the transgenic mice. Light
      microscopic examination revealed that DOX-induced myocardial morphological
      changes were markedly suppressed or almost eliminated in the transgenic mice.
      Under electron microscopy, extensive sarcoplasmic vacuolization and severe
      disruption of mitochondrial fine structure were observed in nontransgenic
      cardiomyocytes, but almost no sarcoplasmic vacuolization was observed, and the
      mitochondrial structural changes were almost completely prevented in the
      transgenic cardiomyocytes. The results thus indicate that MT elevation is a
      highly effective approach to prevent chronic cardiomyopathy attributable to DOX.
      This study also suggests that oxidative stress is critically involved in the DOX
      induced chronic cardiotoxicity.

PMID- 11309297
TI  - Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T
      cell responses against antigens expressed by primary and metastatic tumors.
AB  - Although renal cell carcinoma has been shown to respond to immunotherapy, renal
      cell carcinoma-specific rejection antigens and their corresponding CTL epitopes
      have rarely been described. The use of dendritic cells (DCs) transfected with
      mRNA isolated from tumor cells may allow specific immunotherapy even in cancers
      for which potent rejection antigens have not been identified. Here we show that
      DCs transfected with RNA isolated from renal cancer tissue are remarkably
      effective in stimulating tumor-specific T-cell response in vitro but do not cross
      react with normal tissue antigens including antigens expressed by renal
      parenchyma. In contrast, the tumor-specific CTLs lysed allogeneic tumor but not
      allogeneic normal tissue targets, suggesting the presence of shared albeit
      unidentified antigens among renal carcinomas. CTL responses against telomerase
      reverse transcriptase (TERT) accounted in part for the reactivities against
      allogeneic tumors because renal tumor RNA-transfected DCs stimulated polyclonal
      CTL responses, which encompassed as a subcomponent a response against TERT.
      Nonetheless, the tumor-specific CTLs were consistently superior to the CTLs
      stimulated with TERT RNA-transfected DCs in recognizing and lysing tumor targets,
      suggesting that tumor-specific CTLs represent a polyclonal response providing
      more effective antitumor activity than T-cell responses directed against a single
      antigen in the form of TERT. Tumor RNA-transfected DCs were capable of
      stimulating T-cell reactivities not only against the primary tumor but also
      against metastatic tumors, although discrete differences in the antigenic
      repertoire expressed by these tissues were apparent. Thus, total tumor RNA
      transfected DCs may represent a broadly applicable vaccine strategy to induce
      polyclonal and potentially therapeutic T-cell responses in renal cancer patients.

PMID- 11309298
TI  - E1A sensitizes HER2/neu-overexpressing Ewing's sarcoma cells to topoisomerase II
      targeting anticancer drugs.
AB  - Overexpression of the HER2/neu oncogene is associated with tumorigenicity and
      drug resistance in many types of cancer. Three different human Ewing's sarcoma
      cell lines (TC71, RD, and A4573) were found to express high levels of the
      HER2/neu protein. Transduction of TC71 cells with the E1A gene using an
      adenoviral vector (Ad-E1A) down-regulated HER2/neu overexpression in those cells
      and increased cytostasis. E1A-induced apoptosis was demonstrated by both flow
      cytometric analysis and Western blot analysis using a poly(ADP-ribose) polymerase
      antibody. After transduction of the E1A gene into these cells, the sensitivity of
      these cells to VP-16 (etoposide) was enhanced 18-fold and to Adriamycin 5-fold.
      However, no change was seen in cisplatin sensitivity. E1A also significantly
      increased topoisomerase IIalpha protein expression, indicating that the up
      regulation of topoisomerase IIalpha may be one of the mechanisms by which E1A
      enhanced the sensitivity to topoisomerase II-targeting anticancer drugs, such as
      VP-16 and Adriamycin, but not cisplatin. In summary, these studies demonstrated
      that Ad-E1A can down-regulate HER2/neu overexpression and up-regulate
      topoisomerase IIalpha expression in human Ewing's sarcoma cells, increasing their
      apoptosis rate and enhancing their sensitivity to VP-16 and ADRIAMYCIN:

PMID- 11309299
TI  - A role of interferon-gamma (IFN-gamma) in tumor immunity: T cells with the
      capacity to reject tumor cells are generated but fail to migrate to tumor sites
      in IFN-gamma-deficient mice.
AB  - IFN-gamma-deficient (IFN-gamma-/-) mice induce potent in vitro immune responses
      such as anti-allo mixed lymphocyte reaction and CTL responses, whereas they often
      fail to exhibit in vivo immunity. Here, we investigated whether there exists a
      defect in tumor rejection responses and if so, which process of responses is
      impaired. IFN-gamma-/- and wild-type (WT) BALB/c mice were immunized with
      attenuated syngeneic CSA1M tumor cells. The capacity of T cells to mediate tumor
      protection was examined in Winn assays to assess the growth of tumor cells
      admixed with tumor-sensitized T cells. Splenic T cells from both groups of mice
      exhibited comparable levels of tumor-neutralizing activity. When portions of
      immunized mice were directly challenged with viable tumor cells, tumor rejection
      was induced only in WT mice. CD4(+) and CD8(+) T-cell infiltration were observed
      at the site of tumor challenge in WT mice, whereas such a T-cell infiltration did
      not occur in IFN-gamma-/- mice. Similarly, splenic T cells from interleukin 12
      treated CSA1M-bearing IFN-gamma-/- and WT mice neutralized tumor cells at
      comparable efficacies in Winn assays. However, the migration of these T cells to
      tumor masses and the resultant interleukin 12-induced tumor regression took place
      in WT mice, but neither intratumoral T-cell infiltration nor tumor regression
      occurred in IFN-gamma-/- mice. These results indicate a critical requirement for
      IFN-gamma in the process of inducing T-cell migration to tumor sites rather than
      of generating antitumor protective T cells.

PMID- 11309300
TI  - Beta-catenin mutations in biliary tract cancers: a population-based study in
      China.
AB  - beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial
      role in both cadherin-mediated cell-cell adhesion and as a downstream signaling
      molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta
      catenin gene, at the phosphorylation sites for ubiquitination and degradation of
      beta-catenin, are present in a variety of cancers. Because alterations of the
      adenomatous polyposis coli (APC) gene are present in biliary tract cancers and
      the APC protein modulates levels of beta-catenin, we evaluated the role of beta
      catenin in biliary tract cancer by sequencing the third exon of the beta-catenin
      gene among 107 biliary tract cancers and 7 gallbladder adenomas from a population
      based study in CHINA: Point mutations of serine or threonine phosphorylation
      sites in exon 3 of beta-catenin were present in 8 of 107 (7.5%) biliary tract
      cancers and 4 of 7 (57.1%) gallbladder adenomas. Mutations of beta-catenin were
      more frequent in ampullary and gallbladder carcinomas than in bile duct
      carcinomas (P = 0.04) and in papillary adenocarcinomas than other histological
      types of carcinomas (P = 0.02). These results suggest that the molecular pathways
      of biliary tract neoplasms vary by anatomical subsite and histological subtype.

PMID- 11309301
TI  - Epigenetic patterns in the progression of esophageal adenocarcinoma.
AB  - Esophageal adenocarcinoma (EAC) arises after normal squamous mucosa undergoes
      metaplasia to specialized columnar epithelium (intestinal metaplasia or Barrett's
      esophagus), which can then ultimately progress to dysplasia and subsequent
      malignancy. Epigenetic studies of this model have thus far been limited to the
      DNA methylation analysis of a few genes. In this study, we analyzed a panel of 20
      genes using a quantitative, high-throughput methylation assay, METHYLIGHT: We
      used this broader approach to gain insight into concordant methylation behavior
      between genes and to generate epigenomic fingerprints for the different
      histological stages of EAC. Our study included a total of 104 tissue specimens
      from 51 patients with different stages of Barrett's esophagus and/or associated
      adenocarcinoma. We screened 84 of these samples with the full panel of 20 genes
      and found distinct classes of methylation patterns in the different types of
      tissue. The most informative genes were those with an intermediate frequency of
      significant hypermethylation [ranging from 15% (CDKN2A) to 60% (MGMT) of the
      samples]. This group could be further subdivided into three classes, according to
      the absence (CDKN2A, ESR1, and MYOD1) or presence (CALCA, MGMT, and TIMP3) of
      methylation in normal esophageal mucosa and stomach, or the infrequent
      methylation of normal esophageal mucosa accompanied by methylation in all normal
      stomach samples (APC). The other genes were less informative, because the
      frequency of hypermethylation was below 5% (ARF, CDH1, CDKN2B, GSTP1, MLH1,
      PTGS2, and THBS1), completely absent (CTNNB1, RB1, TGFBR2, and TYMS1), or
      ubiquitous (HIC1 and MTHFR), regardless of tissue type. Each class undergoes
      unique epigenetic changes at different steps of disease progression of EAC,
      suggesting a step-wise loss of multiple protective barriers against CpG island
      hypermethylation. The aberrant hypermethylation occurs at many different loci in
      the same tissues, suggestive of an overall deregulation of methylation control in
      EAC tumorigenesis. However, we did not find evidence for a distinct group of
      tumors with a CpG island methylator phenotype. Finally, we found that normal and
      metaplastic tissues from patients with evidence of associated dysplasia or cancer
      had a significantly higher incidence of hypermethylation than similar tissues
      from patients with no further progression of their disease. The fact that the
      samples from these two groups of patients were histologically indistinguishable,
      yet molecularly distinct, suggests that the occurrence of such hypermethylation
      may provide a clinical tool to identify patients with premalignant Barrett's who
      are at risk for further progression.

PMID- 11309302
TI  - p16(INK4a) and histology-specific methylation of CpG islands by exposure to
      tobacco smoke in non-small cell lung cancer.
AB  - The p16(INK4a) protein inhibits cyclin-dependent kinase 4, a key regulator of
      progression through the G(1) phase of the cell cycle. Methylation of CpG islands
      in the promoter region is an important avenue for inactivation of p16. The
      mechanism of methylation of the p16 promoter region, however, has not been
      elucidated. Recent reports investigating p16 methylation in non-small cell lung
      cancer (NSCLC) suggest that carcinogens in tobacco smoke induce the DNA
      methylation process. We investigated the association between methylation of the
      p16 promoter region and exposure to tobacco smoke in 185 primary NSCLCS: We also
      studied the relationship of p16 methylation with mutation of the K-ras and p53
      genes, as well as with methylation at the DAP-kinase and p14(ARF) loci. Finally,
      we evaluated the prognostic significance of p16 methylation in NSCLC. The
      prevalence of p16 methylation was greater in squamous cell carcinoma (41%)
      compared with adenocarcinoma (22%; P = 0.03; Fisher's exact test). Methylation of
      p16 was significantly associated with pack-years smoked (P = 0.007; Wilcoxon rank
      sum test), duration of smoking (P = 0.0009; Wilcoxon rank sum test), and
      negatively with the time since quitting smoking (P = 0.03; Wilcoxon rank sum
      test). No methylation of the nearby p14(ARF) locus was detected, and methylation
      of the DAP-kinase locus was not associated with either p16 methylation or with
      exposure to tobacco smoke. In patients with stage 1 adenocarcinoma, p16
      methylation was an independent risk factor predicting significantly shorter
      postsurgery survival (P = 0.03), controlling for the significant effects of other
      factors, including K-ras mutation. These findings suggest that methylation of CpG
      islands in tobacco-associated cancers occurs in a gene- and tissue-specific
      manner and is induced directly or indirectly by exposure to tobacco smoke in
      NSCLC.

PMID- 11309303
TI  - Cloning of a new member of the human kallikrein gene family, KLK14, which is down
      regulated in different malignancies.
AB  - Kallikreins (KLKs) belong to the serine protease family of proteolytic enzymes.
      Human pancreatic/renal KLK (KLK1) encodes for an enzyme that is involved in
      posttranslational processing of polypeptide precursors. The function of the other
      members of this gene family is currently unknown, but growing evidence suggests
      that many KLKs are implicated in carcinogenesis. By using the positional
      candidate approach, we were able to identify a new human KLK-like gene, KLK14
      (also known as KLK-L6). This new gene maps to chromosome 19q13.3-q13.4 and is
      formed of seven exons (two untranslated and five coding exons) and six
      intervening introns. KLK14 was defined as a KLK gene based on structural and
      mapping criteria, in relation to other known KLK genes. KLK14 is expressed in a
      variety of tissues, but the highest levels of KLK14 are found in the central
      nervous system, including brain, cerebellum, and spinal cord. Our preliminary
      results show that KLK14 is down-regulated, at the mRNA level, in breast,
      testicular, prostatic, and ovarian cancer.

PMID- 11309304
TI  - Gestational age and gender-specific in utero V(D)J recombinase-mediated
      deletions.
AB  - Recent studies have brought to the forefront the importance of somatic mutations
      during human fetal development and malignant transformation in children,
      specifically leukemia. Therefore, a better understanding of the frequency and
      mutational spectrum of spontaneous in utero mutations is essential for
      understanding the genetic mechanisms associated with pediatric malignancies.
      Previously we reported that the frequency of somatic mutations during the late
      stages of fetal development was dependent on both gestational age and gender.
      Here we present the hypoxanthine-guanine phosphoribosyltransferase (HPRT)
      reporter gene mutational spectra analysis for 60 T-cell mutant isolates from the
      umbilical cord blood of preterm newborns to gain insight into background
      mutational events during the late stages of fetal development. Logistic
      regression analyses showed a significant increase in HPRT deletions mediated by
      V(D)J recombinase in preterm newborns compared with full-term newborns (P =
      0.009). A comparative analysis of deletion mutations also revealed that V(D)J
      recombinase-mediated HPRT deletions increased with decreasing gestational age (P
      = 0.012) and were significantly higher in females than males of the same
      developmental status (P = 0.031). Developmental and gender-specific differences
      in HPRT deletions mediated by V(D)J recombinase provide insight into the gender
      specific differences seen in infant leukemia.

PMID- 11309305
TI  - Partial deletions of the long and short arm of chromosome 3 point to two tumor
      suppressor genes in uveal melanoma.
AB  - Uveal melanoma is the most common form of primary eye cancer. Monosomy 3, which
      is an unusual finding in tumors but is present in approximately 50% of uveal
      melanomas, is significantly correlated with metastatic disease. To obtain
      positional information on putative tumor suppressor genes on this chromosome, we
      have investigated tumors from 333 patients by comparative genomic hybridization,
      microsatellite analysis, or conventional karyotype analysis. A partial deletion
      of the long arm was found in eight tumors, and the smallest region of deletion
      overlap (SRO) spans 3q24-q26. We found six tumors with a partial deletion of the
      short arm and were able to define a second SRO of about 2.5 Mb in 3p25. This SRO
      does not overlap with the VHL gene. Our finding suggests a role for two tumor
      suppressor genes in metastasizing uveal melanoma and may explain the loss of an
      entire chromosome 3 in these tumors.

PMID- 11309306
TI  - Beclin 1 contains a leucine-rich nuclear export signal that is required for its
      autophagy and tumor suppressor function.
AB  - Beclin 1 encodes a Bcl-2-interacting coiled-coil protein with autophagy and tumor
      suppressor function and is monoallelically deleted in 40-75% of sporadic human
      breast and ovarian cancers. Beclin 1 contains a leucine-rich nuclear export
      signal motif raising the possibility that its autophagy and/or tumor suppressor
      function may require regulated, CRM1-dependent, nucleocytoplasmic transport. In
      this study, we show that wild-type Beclin 1 colocalizes with both
      intracytoplasmic organelles and nuclei in COS7 monkey kidney and MCF7 human
      breast carcinoma cells. Inhibition of CRM1-dependent nuclear export with
      leptomycin B or mutation of the nuclear export signal motif of Beclin 1 results
      in predominantly nuclear localization. Unlike wild-type Beclin 1, the nuclear
      export mutant of Beclin 1 fails to promote nutrient deprivation-induced autophagy
      and fails to inhibit in vitro clonigenicity and in vivo tumorigenicity of MCF7
      cells. Thus, beclin 1 has a leptomycin B-sensitive leucine-rich nuclear export
      signal that is required for its autophagy and tumor suppressor function. These
      findings suggest that the CRM1 nuclear export pathway may be important in the
      functional regulation of autophagic growth control.

PMID- 11309307
TI  - Down-regulation of vascular endothelial growth factor by tissue inhibitor of
      metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis.
AB  - The tissue inhibitor of metalloproteinases-2 (TIMP-2) has at least two
      independent functions, i.e., regulation of matrix metalloproteinases and growth
      promoting activity. We investigated the effects of TIMP-2 overexpression, induced
      by retroviral mediated gene transfer, on the in vivo development of mammary
      tumors in syngeneic mice inoculated with EF43.fgf-4 cells. The EF43.fgf-4 cells
      established by stably infecting the normal mouse mammary EF43 cells with a
      retroviral expression vector for the fgf-4 oncogene, are highly tumorigenic and
      overproduce vascular endothelial growth factor (VEGF). Despite a promotion of the
      in vitro growth rate of EF43.fgf-4 cells overexpressing timp-2, the in vivo tumor
      growth was delayed. At day 17 post-cell injection, the volume of tumor derived
      from TIMP-2-overexpressing cells was reduced by 80% as compared with that
      obtained with control cells. Overexpression of TIMP-2 was associated with a down
      regulation of VEGF expression in vitro and in vivo, a reduction of vessel size,
      density, and blood supply in the induced tumors. In addition, TIMP-2 completely
      inhibited the angiogenic activity of EF43.fgf-4 cell-conditioned medium in vitro
      using a rat aortic ring model. Our findings suggest that overexpression of TIMP-2
      delays growth and angiogenesis of mammary carcinoma in vivo and that down
      regulation of VEGF expression may play an important role in this TIMP-2-mediated
      antitumoral and antiangiogenic effects. Finally the in vivo delivery of TIMP-2,
      as assessed by i.v. injection of recombinant adenoviruses vectors, significantly
      reduced the growth of the EF43.fgf-4-induced tumors. This effect of TIMP-2 was
      shown to be equally comparable with that of angiostatin, a known potent inhibitor
      of angiogenesis.

PMID- 11309308
TI  - Subcellular localization and distribution of the breast cancer resistance protein
      transporter in normal human tissues.
AB  - High expression of the Breast Cancer Resistance Protein (BCRP) gene has been
      shown to be involved in resistance to chemotherapeutic drugs. Knowledge of the
      localization of BCRP protein in normal tissues may help unravel the normal
      function of this protein. Therefore, we characterized the tissue distribution and
      cellular localization of BCRP in frozen sections of normal human tissues. For
      this purpose, we used the recently described monoclonal antibody BXP-34 and
      another independently developed monoclonal antibody directed against BCRP, BXP
      21. Both monoclonal antibodies show specific BCRP plasma membrane staining on
      cytospins obtained from topotecan- or mitoxantrone-selected cell lines, as well
      as from BCRP-transfected cell lines. Immunoprecipitation experiments using either
      BXP-21 or BXP-34 yielded a clear M(r) 72,000 BCRP band from BCRP-overexpressing
      tumor cells. In the topotecan-selected T8 and mitoxantrone-selected MX3 tumor
      cell lines, BCRP turned out to be differentially glycosylated. In contrast to BXP
      34, BXP-21 is able to detect the M(r) 72,000 BCRP protein on immunoblots and is
      reactive with BCRP in formalin-fixed, paraffin-embedded tissues. Using BXP-21 and
      BXP-34, prominent staining of BCRP was observed in placental
      syncytiotrophoblasts, in the epithelium of the small intestine and colon, in the
      liver canalicular membrane, and in ducts and lobules of the breast. Furthermore,
      BCRP was present in veinous and capillary endothelium, but not in arterial
      endothelium in all of the tissues investigated. In the tissues studied, the mRNA
      levels of BCRP were assessed using reverse transcription-PCR, and these
      corresponded with the levels of BCRP protein estimated from immunohistochemical
      staining. The presence of BCRP at the placental syncytiotrophoblasts is
      consistent with the hypothesis of a protective role of BCRP for the fetus. The
      apical localization in the epithelium of the small intestine and colon indicates
      a possible role of BCRP in the regulation of the uptake of p.o. administered BCRP
      substrates by back-transport of substrate drugs entering from the gut lumen.
      Therefore, it may be useful to attempt to modulate the uptake of p.o. delivered
      BCRP substrates, e.g., topotecan or irinotecan, by using a BCRP inhibitor.
      Clinical trials testing this hypothesis have been initiated in our institute.

PMID- 11309309
TI  - Down-regulation of beta-catenin TCF signaling is linked to colonic epithelial
      cell differentiation.
AB  - The beta-catenin TCF pathway is implicated in the regulation of colonic
      epithelial cell proliferation, but its role in the regulation of cell
      differentiation is unknown. The colon carcinoma cell line, Caco-2, spontaneously
      undergoes G(0)/G(1) cell cycle arrest and differentiates along the absorptive
      cell lineage over 21 days in culture. In parallel, we show that beta-catenin-TCF
      activity and complex formation are significantly down-regulated. The down
      regulation of beta-catenin-TCF signaling was independent of APC, which we
      characterized as having a nonsense mutation in codon 1367 in Caco-2 cells, but
      was associated with a decrease in TCF-4 protein levels. Total beta-catenin levels
      increased during Caco-2 cell differentiation, although this was attributable to
      an increase in the membrane, E-cadherin-associated, fraction of beta-catenin.
      Importantly, down-regulation of beta-catenin-TCF signaling in undifferentiated
      Caco-2 cells by three different mechanisms, ectopic expression of E-cadherin,
      wild-type APC, or dominant negative TCF-4, resulted in an increase in the
      promoter activities of two genes that are well-established markers of cell
      differentiation, alkaline phosphatase and intestinal fatty acid binding protein.
      These studies demonstrate, therefore, that in addition to its established role in
      the regulation of cell proliferation, down-regulation of the beta-catenin-TCF
      pathway is associated with the promotion of a more-differentiated phenotype in
      colonic epithelial cells.

PMID- 11309310
TI  - Mouse intestinal goblet cells expressing SV40 T antigen directed by the MUC2
      mucin gene promoter undergo apoptosis upon migration to the villi.
AB  - Mucinous colorectal cancers exhibit a characteristic set of molecular genetic
      alterations and may be derived from progenitor cells committed to the goblet cell
      lineage. Previously, we demonstrated that the MUC2 mucin gene promoter drives
      transgene reporter expression with high specificity in small intestinal goblet
      cells of transgenic mice. On the basis of these experiments, we reasoned that the
      MUC2 promoter could be used to drive SV40 T antigen (Tag) expression in the same
      cell type, decoupling them from their normal antiproliferative controls. A line
      of mice was established (MUCTag6) that expressed Tag in intestinal goblet cells
      as determined by RNA blot and immunohistochemical analysis. These goblet cells
      were markedly involuted however, most notably in the villi. Endogenous intestinal
      MUC2 message levels were reduced to about one third the normal level in these
      mice. However, absorptive cell lineage markers were comparable with
      nontransgenics. Bromodeoxyuridine-positive S-phase cells are limited to crypts in
      nontransgenic intestine but are present in both crypts and villi in MUCTag6. In
      contrast, mitotic cells were not present in the villi, indicating that MUCTag6
      villi goblet cells do not progress into M phase. Apoptotic cells positive for
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling were
      increased more than fourfold in MUCTag6 villi (P < 0.0001), and apoptotic goblet
      cells were evident. Electron microscopic examination of MUCTag6 intestinal villi
      revealed the presence of degraded cell remnants containing mucin goblets together
      with other cell debris, further indicating apoptosis of the goblet cell lineage.
      Thus, the expression of Tag in intestinal goblet cells releases them from normal
      antiproliferative controls, causing their inappropriate entry into S phase even
      after they transverse the crypt/villus junction. They do not, however, progress
      to M phase. Instead, they undergo apoptosis with a high degree of efficiency in S
      or G(2) phase. These experiments demonstrate that apoptosis effectively blocks
      inappropriate goblet cell proliferation in the intestine, supporting its proposed
      role as an antineoplastic mechanism.

PMID- 11309311
TI  - Genetic background affects susceptibility to mammary hyperplasias and carcinomas
      in Apc(min)/+ mice.
AB  - Treatment of female C57BL/6J (B6) mice carrying the mutant Min allele of the
      adenomatous polyposis coli (Apc) gene with ethylnitrosourea (ENU) results in
      approximately 90% of mice developing an average of three mammary tumors within 65
      days. As a first step in the identification of loci modifying susceptibility to
      ENU-induced mammary tumors and hyperplasias, we have tested ENU-treated
      Apc(Min)/+ (Min/+) mice on several hybrid backgrounds for susceptibility to
      mammary and intestinal tumors. C57BR/cdJxB6 (BRB6) Min/+ mice were more sensitive
      to development of mammary squamous cell carcinomas than B6 Min/+ mice. In
      contrast, Min/+ hybrids between B6 and FVB/NTac (FVB), 129X1/SvJ (129X1), and
      129S6/SvEvTac (129S6) were all significantly more resistant to mammary carcinoma
      development. However, mice from these three crosses developed more focal mammary
      hyperplasias than did the B6 or BRB6 Min/+ mice. Susceptibility to intestinal
      tumors was independent of mammary tumor susceptibility in most hybrids. These
      results indicate that genetic background can affect independently the phenotypes
      conferred by the Min allele of APC:

PMID- 11309312
TI  - Increased activator protein 1 activity as well as resistance to heat-induced
      radiosensitization, hydrogen peroxide, and cisplatin are inhibited by
      indomethacin in oxidative stress-resistant cells.
AB  - It has been established that tumor cells develop resistance to a variety of
      therapeutic agents after multiple exposures to these agents/drugs. Many of these
      therapeutic agents also appear to increase the activity of transcription factors,
      such as activator protein 1 (AP-1), believed to be involved in cellular responses
      to oxidative stress. Therefore, we hypothesized that cellular resistance to
      cancer therapeutic agents may involve the increased activity of transcription
      factors that govern resistance to oxidative stress, such as AP-1. To investigate
      this hypothesis, a previously characterized cisplatin, hyperthermia, and
      oxidative stress-resistant Chinese hamster fibroblast cell line, OC-14, was
      compared to the parental HA-1 cell line. Electrophoretic mobility shift and
      Western blot assays performed on extracts isolated from OC-14 cells demonstrated
      a 10-fold increase in constitutive AP-1 DNA-binding activity as well as increased
      constitutive c-Fos and c-Jun immunoreactive protein relative to HA-1 cells.
      Treatment of OC-14 cells with indomethacin inhibited constitutive increases in AP
      1 DNA-binding activity and c-Fos/c-Jun-immunoreactive protein levels. Clonogenic
      survival assays demonstrated that pretreatment with indomethacin, at
      concentrations that inhibited AP-1 activity, significantly reduced the resistance
      of OC-14 cells to heat-induced radiosensitization, hydrogen peroxide, and
      cisplatin. These results demonstrate a relationship between increases in AP-1 DNA
      binding activity and increased cellular resistance to cancer therapeutic agents
      and oxidative stress that is inhibited by indomethacin. These results support the
      hypothesis that inhibition of AP-1 activity with nonsteroidal anti-inflammatory
      drugs, such as indomethacin, may represent a useful adjuvant to cancer therapy.

PMID- 11309313
TI  - An intracellular form of cathepsin B contributes to invasiveness in cancer.
AB  - Cathepsin B is a lysosomal cysteine proteinase whose expression and trafficking
      are frequently altered in cancer, and plasma membrane and secreted forms are
      thought to contribute to the invasive and metastatic properties of malignant
      tumors. We have manipulated the expression of cathepsin B in several tumor cell
      lines and measured their capacity to invade through a reconstituted extracellular
      (Matrigel) matrix. Transient expression of human cathepsin B in a poorly
      metastatic B16F1 murine melanoma variant produced a 3-5-fold increase in
      cathepsin B activity and a comparable increase in invasiveness. Stable antisense
      cathepsin B-expressing clones of the highly metastatic human melanoma A375M and
      prostate carcinoma PC3M cell lines produced 40-50% less cathepsin B than control
      cells and were proportionately less invasive. In contrast, manipulating cathepsin
      B levels had no effect on cell migration across an uncoated membrane. The anionic
      cathepsin B inhibitor (L-3-trans-propylcarbamoyloxirane-2-carbony)-L-isoleucyl-L
      proline (CA-074), at a concentration of 1 microM, caused a nearly quantitative
      inhibition of extracellular cathepsin B but had no effect on Matrigel invasion.
      In contrast, the equally potent but less selective inhibitor, trans-epoxysuccinyl
      L-leucylamino(4-guanidino)butane (E-64) inhibited invasion by 75%. Surprisingly,
      at a concentration of 10 microM, CA-074 slowly permeated the cells, causing an 80
      95% inhibition of intracellular cathepsin B after 12 h, the duration of the
      invasion assay. The membrane-permeant cathepsin B inhibitor, CA-074 methyl ester,
      and the higher concentration of CA-074 that inhibited intracellular cathepsin B
      both significantly reduced Matrigel invasion. Collectively, these results
      identify an intracellular role for cathepsin B in matrix degradation. They also
      indicate that caution should be exercised in assuming that CA-074 is unable to
      enter cells when it is used to inhibit biological processes of long duration.

PMID- 11309314
TI  - Viruses as antitumor weapons: defining conditions for tumor remission.
AB  - Recent research has indicated that viruses specifically infecting tumor cells
      could be used as an alternative therapeutic approach in cancer patients. A
      particular example is the adenovirus ONYX-015, which has entered clinical trials
      in the context of head and neck cancer. Successful therapy crucially requires an
      understanding about how viral and host parameters influence tumor load. The
      interactions between the growing tumor, the replicating virus, and possible
      immune responses are multifactorial and nonlinear. Hence, a complete
      understanding of how virus and host characteristics influence the outcome of
      therapy requires mathematical models. In this study, such mathematical models are
      presented and analyzed. The study investigates three possible scenarios that
      could be relevant for therapy: (a) viral cytotoxicity alone kills tumor cells;
      (b) a virus-specific lytic CTL response contributes to killing of infected tumor
      cells; (c) the virus elicits immunostimulatory signals within the tumor that
      promote the development of tumor-specific CTL. The models precisely define
      conditions required for successful therapy. They identify the parameters that
      need to be measured and modulated to evaluate and refine the existing therapy
      regimes.

PMID- 11309315
TI  - Down-regulation of E-cadherin gene expression by collagen type I and type III in
      pancreatic cancer cell lines.
AB  - E-cadherin-mediated cell-cell adhesion is reduced in epithelial tumors, which is
      thought to be a prerequisite to acquire invasive properties. We observed that
      several pancreatic carcinoma cell lines with high metastatic potential expressed
      normal levels of E-cadherin and possessed functional E-cadherin/catenin adhesion
      complexes. When the cell lines PANC-1, BxPC-3, and PaTu8988s were cultured either
      on type I or type III collagen, E-cadherin gene expression was repressed, and E
      cadherin and catenin protein concentrations were reduced. In contrast, growth on
      fibronectin and collagen type IV had no influence. Collagen type I- or type III
      dependent reduction of E-cadherin expression led to decreased cell-cell adhesion,
      increased proliferation, and migratory activity as well as morphological
      transformation. Overexpression of activated c-Src in PANC-1 cells mimicked
      collagen-induced E-cadherin down-regulation and changed the elevated cell
      proliferation and migration. Conversely, treatment of cells with the Src
      inhibitors PP1 or herbimycin A resulted in complete suppression of collagen type
      I-induced E-cadherin decrease. Our data demonstrate that specific collagens are
      able to promote metastatic behavior by down-regulation of E-cadherin gene
      expression in a Src-kinase-dependent manner. This points toward a novel mechanism
      for substrate-dependent signaling and underlines the significance of
      extracellular matrix environment for tumor growth and invasiveness.

PMID- 11309316
TI  - Interleukin 12-activated lymphocytes influence tumor genetic programs.
AB  - T-lymphocytes (LYs) from normal and IFN-gamma knockout mice were activated by
      anti-CD3 and anti-CD28 antibodies and cultured in inserts in the presence of
      interleukin (IL)-12 (IL-12-activated LYs) or not (activated LYs). Their ability
      to modulate the genetic programs of two tumor lines growing at the bottom of
      transwells was evaluated. cDNA gene expression array, reverse transcription-PCR,
      and protein expression showed that LPS, transcription termination factor 1,
      transforming growth factor, and fibroblast growth factor genes were up-modulated
      by factors other than IFN-gamma released by activated LYS: The high levels of IFN
      gamma released by normal IL-12-activated LYs up-modulated the expression of
      STAT1, IRF-1, LMP2, LMP7, monokine induced by IFN-gamma, monocyte chemoattractant
      protein 1, and angiopoietin 2 genes but down-modulated the expression of vascular
      endothelial growth factor. PA28, IFN-inducible protein 10, inducible NO
      synthetase, and macrophage-inhibitory protein 2 genes were up-modulated by
      factors released only by IL-12-activated LYs apart from IFN-gamma. The opposite
      modulations of vascular endothelial growth factor expression and of angiopoietin
      2, monokine induced by IFN-gamma, IFN-inducible protein 10, and inducible NO
      synthetase by IL-12-activated LYs fit in well with the inhibition of angiogenesis
      that characterizes the antitumor activity of IL-12. T-LYs thus modify a tumor's
      behavior so that it becomes a party to its own inhibition.

PMID- 11309317
TI  - Third international Dresden symposium on immunotherapy of cancer.

PMID- 11309319
TI  - Inhibitors of histone deacetylase are potentially effective anticancer agents.

PMID- 11309320
TI  - Technology transfer: a review for biomedical researchers.
AB  - Why is technology transfer important for cancer and other biomedical researchers?
      What do biomedical researchers need to know about technology transfer? This
      report will address these questions in the context of the United States
      technology transfer system, which is now approximately 20 years old. To
      accomplish this goal, this report first summarizes the importance of technology
      transfer and the role of intellectual property rights. Then it describes the
      sequential steps in technology transfer from universities to industry. Next, it
      describes technology transfer from the NIH intramural laboratories and other
      federal laboratories to industry. Finally, it describes unique aspects of
      technology transfer involving clinical trials. URL citations to the latest
      federal guidelines and regulations governing technology transfer are provided.
      Where appropriate, comparisons will be made with technology transfer systems in
      other countries. I hope that this step-by-step description of the technology
      transfer process will enable cancer researchers to play a more proactive role in
      this process and thus increase the likelihood that their discoveries will be
      successfully commercialized. I also hope that this report will assist such
      researchers to understand the policy and institutional considerations that
      underlie current debates concerning technology transfer.

PMID- 11309321
TI  - Pharmacologic interruption of the mitogen-activated extracellular-regulated
      kinase/mitogen-activated protein kinase signal transduction pathway: potential
      role in promoting cytotoxic drug action.

PMID- 11309322
TI  - Role of tumor necrosis factor on toxicity and cytokine production after isolated
      hepatic perfusion.
AB  - PURPOSE: Isolated limb or liver perfusion with tumor necrosis factor (TNF) and
      melphalan results in regression of advanced cancers in the majority of treated
      patients. However, the contribution of TNF to the efficacy of isolation perfusion
      with melphalan has not been demonstrated conclusively in random assignment
      trials. Furthermore, TNF is an inflammatory cytokine and may be associated with
      significant systemic and regional toxicity. This study was conducted to
      characterize the toxicity and secondary cytokine production attributable to TNF
      by comparing these parameters in patients undergoing isolated hepatic perfusion
      (IHP) using melphalan with or without TNF. EXPERIMENTAL DESIGN: Thirty-two
      patients with unresectable colorectal cancer confined to the liver underwent a 60
      min hyperthermic IHP using 1.5 mg/kg melphalan alone (n = 17) or with 1.0 mg of
      TNF (n = 15) with inflow via the gastroduodenal artery and outflow via an
      isolated segment of inferior vena cava. Complete vascular isolation was confirmed
      using the I-131 radiolabeled albumin-monitoring technique. Post-IHP parameters of
      hepatic and systemic toxicity and cytokine levels [TNF, interleukin (IL)-6 and IL
      8] in perfusate and serum were measured. RESULTS: Levels of IL-6 and IL-8 in
      perfusate at the end of the 60-min IHP were significantly higher in TNF-treated
      patients (P < or = 0.001). Peak systemic IL-6 and IL-8 levels post-IHP were also
      significantly higher in TNF-treated compared with non-TNF-treated patients (P <
      0.0001) by 28- and 268-fold, respectively. The peak levels of these cytokines
      were associated with significantly lower systolic blood pressure and higher heart
      rate and mean pulmonary artery blood pressure in TNF-treated patients during the
      first 48 h post-IHP (P < or = 0.03). Serum bilirubin levels were significantly
      higher (P = 0.017) and platelets lower (P = 0.03) in TNF-treated compared with
      non-TNF-treated patients. However, elevations in aspartate aminotransferase,
      alanine aminotransferase, and alkaline phosphatase were not significantly
      different between groups and returned toward baseline within 1 week after IHP.
      CONCLUSIONS: Addition of TNF to melphalan during IHP results in significant
      differences in post-IHP production of IL-6 and IL-8 with associated changes in
      mean arterial blood pressure and greater regional toxicity, as reflected in
      higher levels of serum bilirubin. However, these measurable differences were
      transient and did not appear to be of major clinical consequence. Prior to its
      routine use, the benefit of TNF in isolation perfusion should be demonstrated in
      random assignment trials.

PMID- 11309323
TI  - Future development of lymphoproliferative disorders in patients with autoimmune
      hemolytic anemia.
AB  - The association between autoimmune hemolytic anemia (AIHA) and subsequent
      appearance of lymphoproliferative disorders (LPDs) has not been properly
      addressed in large-scale studies. We evaluated 107 patients with idiopathic (67
      patients) or underlying (40 patients) immune disorders diagnosed with AIHA
      between 1992 and 1999. The following variables were examined in univariate and
      multivariate analysis: age; sex; type of AIHA (warm- or cold-active antibodies);
      presence of underlying immune disorders; and serum monoclonal protein. Of the 107
      patients, 19 (18%) developed malignant LPDS: The median time to develop
      malignancy was 26.5 months (range, 9-76 months). At multivariate analysis,
      advanced age (P = 0.005), underlying autoimmune diseases (P = 0.002), and the
      presence of serum gammopathy (P = 0.045) were risk factors for future development
      of LPDs in these patients. Also, serum monoclonal IgM protein was a significant
      predictor (P = 0.0001) for the appearance of LPDs in patients with AIHA. The
      present study provides evidence that AIHA in some patients should be considered
      as a precursor of malignant LPDS: Knowledge of certain characteristics may help
      identify patients at risk for this transformation; periodic clinical and
      laboratory assessment of these patients is warranted.

PMID- 11309324
TI  - High levels of vascular endothelial growth factor receptor-2 correlate with
      shortened survival in chronic lymphocytic leukemia.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR-2), also termed KDR, is a
      high-affinity vascular endothelial growth factor (VEGF) receptor. VEGFR-2 plays a
      role in de novo blood vessel formation and hematopoietic cell development.
      Recently, we found that chronic lymphocytic leukemia (CLL) cells express high
      levels of VEGF. Therefore, we sought to investigate the role of VEGFR-2 in CLL.
      Using Western blot analysis, we first determined that VEGFR-2 is present in
      peripheral blood CLL cells. We then quantified the cellular levels of VEGFR-2
      protein using a solid-phase radioimmunoanalysis in peripheral blood cells from
      216 patients with CLL. As control, we used peripheral blood mononuclear cells
      (PBMNCs) from 31 hematologically normal individuals. The median of VEGFR-2 levels
      detected in the control samples was assigned a value of 1.0, and VEGFR-2 protein
      levels were normalized to the control median value. The median level of VEGFR-2
      in CLL cells was 1.57. Patients with VEGFR-2 levels higher than 1.57 had elevated
      lymphocyte counts, severe anemia, elevated beta(2)-microglobulin and advanced
      stage disease. Elevated VEGFR-2 levels were also associated with statistically
      significantly shorter survival (35.4 versus 60.1 months; P < 0.01). Our data
      indicate that cellular VEGFR-2 levels may serve as a prognostic factor in CLL.
      Further studies should investigate the biological implications of these findings
      and the effect of the interaction between VEGF and VEGFR-2 on CLL cell
      proliferation.

PMID- 11309325
TI  - A multi-institutional phase ii study of SU101, a platelet-derived growth factor
      receptor inhibitor, for patients with hormone-refractory prostate cancer.
AB  - In a multi-institutional Phase II trial, we evaluated the efficacy of a platelet
      derived growth factor receptor (PDGF-r) inhibitor, SU101, in patients with
      hormonerefractory prostate cancer. The patients received a 4-day i.v. loading
      dose of SU101 at 400 mg/m(2) for 4 consecutive days, followed by 10 weekly
      infusions at 400 mg/m(2). The primary study end points were a decline in prostate
      specific antigen (PSA) and a decrease in measurable tumor. Secondary end points
      were time to progression and an effect on pain as measured by the Brief Pain
      Survey. Expression of PDGF-r was examined in both metastatic and archival primary
      prostate tumor samples. Forty-four patients were enrolled at four centers. The
      median age was 72 years, the median PSA was 223 ng/ml, and 21 patients had at
      least one prior chemotherapy. Thirty-nine patients are evaluable for PSA, and
      three patients demonstrated a PSA decline >50% from baseline (55-99.9% decrease).
      The median time to progression was 90 days. Of 19 patients evaluable for
      measurable disease, 1 patient had a partial response. Nine of 35 evaluable
      patients had significant improvement in pain. The most frequent adverse events
      were asthenia (75%), nausea (55%), anorexia (50%), and anemia (41%). PDGF-r
      expression was detected in 80% of the metastases and 88% of primary prostate
      cancers. The results of this trial may warrant further clinical studies with
      other PDGF-r inhibitors.

PMID- 11309327
TI  - Expression of the tumor suppressor gene Maspin in human pancreatic cancers.
AB  - The tumor suppressor gene maspin, a unique member of the serpin superfamily,
      inhibits cell motility, invasion, and metastasis in breast and prostate cancers.
      Maspin is expressed in normal human mammary and prostate epithelial cells but
      down-regulated during cancer progression. In this study, we analyzed the
      expression of maspin in various human cancer cells by means of Northern blot and
      immunohistochemistry. Maspin gene expression proved to be up-regulated in
      pancreatic cancer. Maspin expression was not detected in any of 6 gastric
      cancers, 4 melanomas, or 6 of 7 breast cancer cell lines examined. In contrast, 5
      of 9 pancreatic cancer cell lines showed maspin expression, although maspin
      expression was not detected in normal pancreatic tissue. Furthermore, maspin was
      expressed in 23 of 24 tumor specimens obtained from pancreatic cancer patients as
      well as all high-grade precancerous lesions (PanIN3 and intraductal carcinoma
      extension). In contrast, no expression was observed in normal and low-grade
      precancerous lesions. Our results show that maspin is a new factor associated
      with pancreatic cancer. In addition, the detection of maspin in pancreatic tumor
      tissues and its lack of expression in all normal pancreatic tissues suggests that
      maspin may be a useful marker of primary human pancreatic cancer.

PMID- 11309326
TI  - The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice
      variants and its prognostic value in ovarian cancer.
AB  - KLK8 (neuropsin/ovasin) is a new member of the human kallikrein gene family,
      which consists of enzymes with serine protease enzymatic activity. Recent reports
      have implicated KLK8 in ovarian cancer. KLK8 may have potential clinical value
      for disease diagnosis or prognosis and it may also be a useful therapeutic
      target. PURPOSE: We undertook this study to evaluate the prognostic value of KLK8
      in ovarian carcinoma by examining its expression in ovarian tumors. EXPERIMENTAL
      DESIGN: The KLK8 gene was analyzed by reverse transcription-PCR and direct
      sequencing in several human normal tissues. Subsequently, its expression was
      studied in a set of ovarian tumors, and statistical analysis was performed.
      RESULTS: We have identified two novel mRNA splice variants of the KLK8 gene,
      which are abundantly expressed in many tissues. These new variants were named
      KLK8 type 3 and type 4. Study of the expression of the KLK8 gene and its spliced
      variants in ovarian tumors indicated that the new variants were expressed very
      frequently and that full-length KLK8 expression is an independent and favorable
      prognostic marker for ovarian cancer. Patients with higher KLK8 expression in the
      tumor have lower grade disease, lower residual tumor left after surgery, live
      longer, and relapse less frequently. In multivariate analysis, higher KLK8
      expression was significantly associated with longer disease-free survival.
      CONCLUSIONS: These results suggest that KLK8 is a novel, favorable prognostic
      marker in ovarian cancer. Because KLK8 encodes for a predicted secreted protein,
      its detection in serum may aid in ovarian cancer diagnosis.

PMID- 11309328
TI  - Association of ARNT splice variants with estrogen receptor-negative breast
      cancer, poor induction of vascular endothelial growth factor under hypoxia, and
      poor prognosis.
AB  - The aryl hydrocarbon receptor nuclear translocator (ARNT) is a basic helix-loop
      helix transcription factor that forms heterodimers with the aryl hydrocarbon
      receptor (AhR) or hypoxia inducible factor-1alpha to activate transcription via
      xenobiotic response element or hypoxia response element, respectively. Thus, it
      plays a major role in two key biochemical pathways involved in tumor growth. We
      previously showed that estrogen receptor (ER)-negative breast cancer cell lines
      expressed a splice variant of ARNT that was associated with Ah nonresponsiveness.
      We have now used a sensitive PCR method to analyze the expression of the variant
      in a series of 92 breast cancers to assess interactions with the ER and
      prognosis. The splice variant could be detected in all of the cases examined,
      with high ratios of variant:full-length ARNT (> or =10) characterized in 10
      cases. When the patient group was split into quartiles by increasing splice
      variant ratios, there was an inverse relationship of ER status to ARNT splice
      variant ratios (P = 0.01, chi(2)). Univariate analysis showed that cases with
      high ARNT splice-variant ratios > or =10 had a worse relapse-free and overall
      survival (P > or = 0.03; hazard ratio, 2.7; and P = 0.006; hazard ratio, 3.9,
      respectively). In multivariate analysis for relapse-free and overall survival,
      ARNT splice-variant ratio was the strongest independent factor and, although
      inversely related to ER, remained a separate risk factor. At least two potential
      mechanisms could explain this phenomenon: the loss of aryl hydrocarbon receptor
      mediated antiestrogenic activity or the blockade of a proapoptotic pathway
      induced by hypoxia. Because several enzymes involved in drug resistance are
      induced through a xenobiotic response element, the tumors presenting high ARNT
      splice-variant ratios may be specifically targeted by drugs normally degraded or
      inactivated. This study shows the biological importance of ARNT splice variants
      in the behavior of human breast cancer and suggests that the breast cell lines in
      which the splice variant was discovered may be useful models for further
      investigation.

PMID- 11309329
TI  - Elevated and altered expression of the multifunctional DNA base excision repair
      and redox enzyme Ape1/ref-1 in prostate cancer.
AB  - The DNA base excision repair pathway is responsible for the repair of cellular
      alkylation and oxidative DNA damage. A crucial step in the BER pathway involves
      the cleavage of baseless sites in DNA by an apurinic/apyrimidinic or baseless
      (AP) endonuclease (Ape1/ref-1), which is a multifunctional enzyme that acts not
      only as an AP endonuclease but also as a redox-modifying factor for a variety of
      transcription factors including Fos, Jun, paired box containing genes (PAX),
      nuclear factor-kappaB, hypoxia-inducible factor alpha (HIF-1alpha), HIF-like
      factor (HLF), p53, and others. The expression of Ape1/ref-1 in prostate has not
      been characterized previously. Ape1/ref-1 nuclear immunohistochemistry levels,
      scored for intensity as 1+, 2+, or 3+, were 91, 3, and 6% in benign hypertrophy
      (BPH), 0, 42, and 58% in prostatic intraepithelial neoplasia (PIN) and 3, 30, and
      67% in prostate cancer, respectively, clearly showing an increase in Ape1/ref-1
      nuclear staining in the PIN and cancer compared with BPH. Furthermore, the level
      of cytoplasmic staining of Ape1/ref-1 in cancer and PIN were elevated (42 and
      36%, respectively) compared with BPH (5%). There was no correlation with prostate
      specific antigen values or doubling times to Ape1/ref-1 levels. In conclusion, we
      have demonstrated that Ape1/ref-1 is dramatically elevated in prostate cancer,
      the level of staining of Ape1/ref-1 increases from low in BPH to intense in PIN
      and cancer, and there is an increase in the amount of Ape1/ref-1 in the cytoplasm
      of PIN and cancer compared with BPH. Given these results, we conclude that
      Ape1/ref-1 may be a diagnostic marker for early prostate cancer and play a role,
      through its repair, redox, or both functions, in the physiology of the early
      development of prostate cancer.

PMID- 11309330
TI  - The p53 mutational spectrum associated with BRCA1 mutant ovarian cancer.
AB  - PURPOSE: Cancer-specific p53 mutational spectra have been identified. Data from
      murine models and human BRCA1-related hereditary breast cancers suggest that both
      unique and specific BRCA1-associated p53 mutations may be found in BRCA1-related
      ovarian cancers. EXPERIMENTAL DESIGN: The p53 mutational spectrum from ovarian
      cancers containing either somatic or germ-line BRCA1 mutations was compared with
      that of sporadic ovarian cancers defined as those diagnosed with a negative
      family history for breast/ovarian cancer in a three-generation pedigree. Tumor
      DNA was screened over exons 2-11 of the p53 gene by the PCR and single-strand
      confirmation polymorphism analysis of the amplimers. Cycle-based DNA sequencing
      from separate reactions was used to confirm p53 mutations. RESULTS: p53 gene
      mutations were detected in 42 of 86 sporadic ovarian cancers, compared with 13 of
      15 cancers with somatic BRCA1 mutations (P = 0.007) and 16 of 20 cancers with
      germ-line BRCA1 mutations (P = 0.01). p53 null mutations were found in 31.4% of
      BRCA1 mutant cancers, compared with only 9.3% of the sporadic cancers (P =
      0.002). The p53 mutational spectrum of germ-line BRCA1-related cancers was
      shifted toward transversions, frameshifts, and non-CpG transitions relative to
      the spectrum of sporadic ovarian cancers. Thirty-three unique ovarian cancer p53
      mutations were sequenced. However, the specific p53 mutations in the BRCA1 mutant
      cancers were no more unique to this cohort than the p53 mutations of the sporadic
      cancers. CONCLUSIONS: Ovarian cancers containing somatic or germ-line BRCA1
      mutations are uniformly accompanied by p53 dysfunction. This finding offers
      additional support to observations regarding the importance of p53/BRCA1
      interactions in ovarian carcinogenesis.

PMID- 11309331
TI  - Molecular subtypes of anaplastic oligodendroglioma: implications for patient
      management at diagnosis.
AB  - PURPOSE: In a prior study of anaplastic oligodendrogliomas treated with
      chemotherapy at diagnosis or at recurrence after radiotherapy, allelic loss of
      chromosome 1p correlated with better chemotherapeutic response and overall
      survival. However, in this group of patients in whom therapeutic management was
      not uniform, loss of 1p did not identify all chemosensitive tumors, nor did all
      patients whose tumors harbor a 1p loss have long survival. EXPERIMENTAL DESIGN:
      To clarify the clinical relevance of molecular genetic testing at the time of
      diagnosis for patients with anaplastic oligodendrogliomas, we studied a larger,
      more homogeneous group of 50 patients with histologically defined anaplastic
      oligodendrogliomas treated with a chemotherapeutic regimen as the principal
      initial therapy. RESULTS: We demonstrate that these tumors can be divided
      genetically into four therapeutically and prognostically relevant subgroups.
      Patients whose tumors have combined but isolated losses of 1p and 19q have marked
      and durable responses to chemotherapy associated with long survival, with or
      without postoperative radiation therapy. Other tumors with chromosome 1p
      alterations also respond to chemotherapy, but with shorter duration of response
      and patient survival. Tumors lacking 1p loss can also be divided into two
      subgroups: those with TP53 mutations, which may also respond to chemotherapy but
      recur quickly, and those without TP53 mutations, which are poorly responsive,
      aggressive tumors that are clinically and genotypically similar to glioblastomas.
      CONCLUSIONS: These data raise the possibility, for the first time, that
      therapeutic decisions at the time of diagnosis might be tailored to particular
      genetic subtypes of anaplastic oligodendroglioma.

PMID- 11309332
TI  - Zinc alpha-2-glycoprotein is expressed by malignant prostatic epithelium and may
      serve as a potential serum marker for prostate cancer.
AB  - Zinc alpha-2-glycoprotein (ZAG) is a M(r) 41,000 glycoprotein secreted by a
      variety of normal epithelia. ZAG was recently shown to stimulate lipolysis in
      adipocytes, leading to the development of cachexia in animals with ZAG-producing
      tumors. To understand the possible contribution of ZAG to the development of
      cachexia in men with prostate cancer, ZAG production by normal and malignant
      prostate tissue was investigated using immunohistochemical assays. Anti-ZAG
      monoclonal antibodies reacted strongly with normal prostate epithelium but not
      with other components of prostate or seminal vesicles. The majority of prostate
      cancers tested (35 of 48; 73%) also reacted with anti-ZAG antibodies. High-grade
      tumors expressed significantly less ZAG than moderate-grade tumors (mean ZAG
      score 1.1 versus 1.9; P < 0.01). Men with ZAG-producing prostate carcinomas had
      elevated levels of serum ZAG relative to their normal age- and race-matched
      controls (P < 0.02). Furthermore, s.c. growth of human ZAG-producing murine
      tumors in syngeneic mice and orthotopic growth of ZAG-producing human prostate
      carcinomas in nude rats resulted in readily detectable levels of human ZAG in the
      serum. Taken together, these studies show that ZAG production by prostate cancer
      can lead to systemically elevated serum ZAG levels that may be useful
      diagnostically. The effects of elevated systemic ZAG on cachexia-associated
      complications in patients with advanced prostate cancer deserves additional
      investigation.

PMID- 11309333
TI  - Semenogelins are ectopically expressed in small cell lung carcinoma.
AB  - Two proteins recovered from cell surface adhesion complexes in a small cell lung
      carcinoma (SCLC) cell line were identified as fragments of the seminal plasma
      proteins semenogelin I and semenogelin II. Association of both proteins with the
      adhesion complexes was induced by epidermal growth factor. Expression of
      semenogelins was previously thought to be highly specific to seminal vesicles,
      but Western blot analysis demonstrated that semenogelin II is widely expressed in
      SCLC cell lines and occasionally in other malignant cell lines. Although
      semenogelin expression is normally restricted to males, two SCLC cell lines from
      female patients were also positive for semenogelin II expression.
      Immunohistochemical analysis demonstrated diffuse expression of semenogelins in
      12 of 13 SCLC tumors and focal expression in a minority of lung squamous and
      adenocarcinomas. Semenogelins were secreted into the medium by cultured SCLC
      cells, which suggested that these proteins may be useful markers for detecting
      residual tumor burden or recurrence of SCLC after treatment.

PMID- 11309334
TI  - Cyclooxygenase-2 overexpression is a marker of poor prognosis in stage I non
      small cell lung cancer.
AB  - Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to
      prostaglandins, is overexpressed in a variety of different tumors, including
      those of the colon, pancreas, lung, and head and neck. We used in situ
      hybridization with a digoxgenin-labeled COX-2 antisense riboprobe to assess the
      presence of strong or intermediate versus weak or absent COX-2 expression in
      specimens from 160 patients with stage I non-small cell lung cancer (NSCLC). Of
      these, 3 specimens had strong expression, 69 had intermediate expression of COX
      2, 24 had weak expression, and 64 had no detectable COX-2. The strength of COX-2
      expression was associated with a worse overall survival rate (P = 0.001) and a
      worse disease-free survival rate (P = 0.022). The median survival times for the
      strong, intermediate or weak, and null COX-2 expressors were 1.04, 5.50, and 8.54
      years, respectively. Interestingly, all three specimens with strong COX-2
      expression came from patients who died within 18 months. Retinoic acid receptor
      beta (RAR-beta) is a nuclear retinoid receptor whose expression is frequently
      lost in aerodigestive tract carcinogenesis. We previously demonstrated that
      expression of RAR-beta in stage I NSCLC indicates a poor prognosis. Retinoids
      have been shown to prevent induction of COX-2 by mitogens and tumor promoters.
      Expression of COX-2 correlated with RAR-beta expression (P = 0.053), but not with
      k-ras mutational status, vascular endothelial growth factor, basic fibroblast
      growth factor, interleukin 8 levels, or other markers of angiogenesis, invasion,
      and metastases. Thus, like RAR-beta positivity, COX-2 overexpression appears to
      portend a shorter survival among patients with early stage non-small cell lung
      cancer. Future studies of RAR-beta and COX-2 regulation in NSCLC should further
      the development of prevention and therapy interventions with retinoids and/or COX
      2 antagonists in this patient population.

PMID- 11309335
TI  - Amplification and expression of splice variants of the gene encoding the P450
      cytochrome 25-hydroxyvitamin D(3) 1,alpha-hydroxylase (CYP 27B1) in human
      malignant glioma.
AB  - PURPOSE: Recently, we reported the isolation of six novel genes termed glioma
      amplified sequences (GASs) from the glioblastoma cell line TX3868 using
      microdissected mediated cDNA capture (U. Fischer et al., HUM: MOL: GENET:, 5: 595
      600, 1996). The aim of this study was to further characterize the gene GAS89.
      EXPERIMENTAL DESIGN: To determine the amplification frequency, we performed
      comparative PCR studies and Southern blot hybridization experiments. To identify
      full-length clones of GAS89 we screened a HybriZAP library. Reverse transcription
      PCR was performed to isolate splice variants and to determine expression levels.
      RESULTS: We identified for the gene GAS89 an amplification frequency of 25% in 28
      examined glioblastoma multiforme samples. Screening a HybriZAP library, we
      isolated an incomplete gene sequence showing identity with the gene for 25
      hydroxyvitamin D(3) 1,alpha-hydroxylase. Different full-length clones were then
      isolated using PCR primers chosen from the 3'- and 5'-untranslated regions. As
      determined by sequencing, the clones represent various splice variants of the 25
      hydroxyvitamin D(3) 1,alpha-hydroxylase gene. The clones encode truncated
      proteins but also one potentially functional enzyme variant. Reverse
      transcription-PCR studies revealed overexpression of several variants in
      glioblastoma samples with GAS89 amplification in comparison with normal brain RNA
      and glioblastoma without GAS89 amplification. CONCLUSIONS: This is the first
      report of gene amplification for 25-hydroxyvitamin D(3) 1,alpha-hydroxylase and
      the appearance of mRNA splice variants in glioblastoma multiforme. The endogenous
      expression of the 25-hydroxyvitamin D(3) 1,alpha-hydroxylase gene and the
      appearance of alternative splice variants reveal a new feature of the molecular
      pathogenesis of glioblastoma and may represent a new target for glioma therapy.

PMID- 11309336
TI  - Allelic losses of loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 correlate with
      postoperative recurrence in breast cancer.
AB  - We previously defined 18 chromosomal regions in which frequent allelic losses
      were observed in breast cancers (T. Sato et al., Cancer RES:, 50: 7184-7189,
      1990; Y. Harada et al., Cancer (PHILA:), 74: 2281-2286, 1994; I. Ito et al., BR:
      J. Cancer, 71: 438-441, 1995; K. Tsukamoto et al., Cancer (PHILA:), 78: 1929
      1934, 1996; S. Matsumoto et al., Genes Chromosomes Cancer, 20: 268-274, 1997; T.
      Yokota et al., JPN: J. Cancer RES:, 88: 959-964, 1997; K. Tsukamoto et al.,
      Cancer (PHILA:), 82: 317-322, 1998; A. Iida et al., Genes Chromosomes Cancer, 21:
      108-112, 1998; K. Fukino et al., Genes Chromosomes Cancer, 24: 345-350, 1999; T.
      Yokota et al., Cancer (PHILA:), 85: 447-452, 1999; Y. Utada et al., JPN: J.
      Cancer RES:, 91: 293-300, 2000). To identify specific allelic losses that might
      correlate with postoperative recurrence, we examined tumors from a cohort of 504
      breast cancer patients, who were followed clinically for 5 years postoperatively,
      for allelic losses of 18 microsatellite markers. Patients whose tumors had lost
      an allele at 3p25.1, 8p22, 13q12, 17p13.3, or 22q13 had significantly higher
      risks of recurrence than those whose tumors retained both alleles at those loci;
      at 3p25.1, the 5-year recurrence rate was 27% among patients with losses versus
      18% with retention (P = 0.0131); at 8p22, 27% versus 14% (P = 0.0129); at 13q12,
      28% versus 15% (P = 0.0109); at 17p13.3, 27% versus 20% (P = 0.0482); and at
      22q13, 29% versus 20% (P = 0.0477). These data indicate that loss of
      heterozygosity at any one of these five specific loci is a significant predictor
      of postoperative recurrence among patients who have undergone surgery for breast
      cancer. These allelic losses can serve as negative prognostic indicators to guide
      postoperative management of patients.

PMID- 11309337
TI  - Frequent inactivation of the TP53 gene in esophageal squamous cell carcinoma from
      a high-risk population in China.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal cancers
      worldwide, and north central China has some of the highest rates in the world.
      Previous studies from tumors in this area of China have shown high frequencies of
      allelic loss on chromosome 17p13-11, which includes the region where the TP53
      gene is found. We examined 56 ESCC patients using single-strand conformation
      polymorphism and DNA sequencing to assess the frequency and spectrum of TP53
      mutation and the association between allelic loss at microsatellite marker TP53
      and TP53 mutations. Ninety-six % of cases were found to have at least one genetic
      alteration, including TP53 mutation (77%), allelic loss within the TP53 gene
      (73%), and/or loss of heterozygosity at the TP53 microsatellite marker (80%); 75%
      had two or more such alterations, including 59% with both a point mutation and an
      intragenic allelic loss ("two hits"). The majority of mutations observed were in
      exon 5, where the most common type of nucleotide substitution was a G:C-->A:T or
      C:G-->T:A transition, including half that occurred at CpG sites. Allelic loss was
      most commonly found in exon 4 but was very common in exon 5 as well. Taken
      together, the multiple genetic alterations of TP53 in this population at high
      risk for ESCC indicate that there is a very high degree of genetic instability in
      these tumors, that TP53 is a primary target for inactivation, and that this tumor
      suppressor gene plays a critical role in the carcinogenesis process for ESCC.

PMID- 11309338
TI  - Correlation between loss of PTEN expression and Akt phosphorylation in
      endometrial carcinoma.
AB  - The tumor suppressor PTEN acts as a lipid phosphatase, regulates the
      phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway, and modulates cell
      cycle progression and cell survival. Somatic mutations of PTEN have been reported
      in a variety of cancers, especially in endometrial carcinoma. To clarify whether
      and how PTEN and the PI3K/Akt pathway relates to endometrial carcinoma, we
      examined the expression of those pathway-related proteins in patients with
      endometrial carcinoma. Of 103 endometrial carcinomas, 37 (36%) showed negative
      immunohistochemical staining of PTEN. Western blotting revealed that the
      expression of PTEN in PTEN-negative cases was significantly lower compared with
      that in positive cases. In contrast, phospho-Akt level in negative cases was
      significantly higher. We found a significant inverse correlation between PTEN and
      phospho-Akt (r = -0.796). The expression of phospho-Bad was greater in negative
      cases, suggesting that Bad might be a target for AKT: The present study
      demonstrates the phosphorylation of Akt accompanied by the loss of PTEN in
      clinical specimens of endometrial carcinomas.

PMID- 11309339
TI  - Expression of the gamma(2) chain of laminin-5 at the invasive front is associated
      with recurrence and poor prognosis in human esophageal squamous cell carcinoma.
AB  - PURPOSE: Preferential expression of the gamma(2) chain of laminin-5 in invading
      carcinoma cells has been implicated in tumor invasion. The aim of this study was
      to clarify the clinicopathological and prognostic significance of laminin
      gamma(2) chain expression in esophageal squamous cell carcinoma (SCC).
      EXPERIMENTAL DESIGN: We analyzed the association between immunohistochemically
      detected laminin gamma(2) chain expression in esophageal SCC and
      clinicopathological characteristics, and we investigated whether laminin gamma(2)
      chain is a predictor of recurrence and/or survival. RESULTS: The cytoplasm of
      carcinoma cells was stained for laminin gamma(2) at levels much stronger than
      those in normal esophageal basement membrane. The immunoreactivities at the
      invasive front were often more intense than those at the superficial layer.
      Sections with immunostaining signals in >30% of carcinoma cells at the invasive
      front, which were observed in 44 of 100 cases, were judged to be positive for
      laminin gamma(2) chain. Laminin gamma(2) chain positivity was significantly
      correlated with depth of invasion, lymph node metastasis, distant metastasis,
      advanced pTNM stage, recurrence, and recurrence within the first postoperative
      year. Patients with laminin gamma(2) chain-positive carcinoma had a significantly
      shorter disease-free and overall survival time than did those with laminin
      gamma(2) chain-negative carcinoma. Laminin gamma(2) chain retained its
      significant predictive value for disease-free and overall survival in
      multivariate analysis that included conventional clinicopathological factors.
      CONCLUSIONS: Our results suggest that the laminin gamma(2) chain plays a key role
      in the progression of esophageal carcinoma and that its detection is useful for
      the prediction of recurrence and poor prognosis.

PMID- 11309340
TI  - Frequent deletions and mutations of the beta-catenin gene are associated with
      overexpression of cyclin D1 and fibronectin and poorly differentiated histology
      in childhood hepatoblastoma.
AB  - Hepatoblastoma (HBL) is the most common malignant liver tumor in young children.
      Recent reports have shown that the beta-catenin gene was frequently mutated or
      deleted in HBLS: To elucidate the role of beta-catenin abnormalities in HBLs, we
      searched for mutations of beta-catenin and APC as well as expression of the
      target genes, cyclin D1, c-myc, and fibronectin, in 68 primary HBLS: The mutation
      analysis revealed that 44 (65%) tumors carried missense mutations or deletions of
      beta-catenin, all of which were somatic and targeted to the exon 3 encoding the
      amino acid residues involved in its degradation. However, no loss of function
      mutation of the APC gene was detected by the yeast functional assay. Of interest,
      beta-catenin mutation was significantly correlated with overexpression of the
      target genes, cyclin D1 and fibronectin, but not with that of c-myc in HBLs as
      measured by quantitative real-time reverse transcription-PCR. The
      immunohistochemical studies in 15 HBLs demonstrated that the nuclear/cytoplasmic
      accumulation of beta-catenin was positive in 13 tumors, 9 of which had the
      deletion or mutation of the gene. The significant correlation between the beta
      catenin gene abnormality and the positive staining of cyclin D1 was also
      confirmed. Furthermore, the nuclear accumulation of beta-catenin was strongly
      associated with the poorly differentiated tumor cell components as well as with
      the positive staining of cyclin D1 within the tumor. Thus, our present results
      suggested that the gain of function mutation of beta-catenin played a crucial
      role in the malignant progression of HBL in vivo.

PMID- 11309341
TI  - S-phase fraction and DNA ploidy in 633 T1T2 breast cancers: a standardized flow
      cytometric study.
AB  - The lack of a standardized methodology for quantifying DNA ploidy and S-phase
      fraction (SPF) by flow cytometry is hindering routine use of these markers in
      breast cancer management. In a retrospective clinical multicenter study, we
      validated a standardized flow cytometry protocol. We tested 633 frozen T(1)T(2),
      N(0)N(1), M(0) breast tumors obtained in four institutions. Cell preparation was
      standardized, and precise rules for data interpretation were followed. Three SPF
      classes were defined on the basis of tertiles after adjustment for ploidy. DNA
      aneuploidy was observed in 61.0% of cases. No significant difference was observed
      among centers. Aneuploidy and high SPF were associated with large tumor size,
      node involvement, high histological grade, and hormone receptor negativity. In
      the overall population (median follow-up, 69 months), patients with medium and
      high SPF values had shorter disease-free survival (DFS) than those with low SPF
      values (P < 0.0001). Ploidy had no significant influence. By Cox analysis, SPF,
      pN, and estrogen receptor status were independent predictors of DFS (P = 0.0002,
      P = 0.001, and P = 0.05). In node-negative patients, SPF was the only predictor
      of DFS (P = 0.01), whereas in node-positive patients, the risk of relapse
      increased with both high SPF (P = 0.003) and estrogen receptor negativity (P =
      0.004). Low SPF values distinguished grade II tumors with a particularly good
      outcome. Our results strongly support the use of SPF in multicenter studies and
      clinical trials and suggest that node-negative patients with slowly proliferating
      tumors do not require systemic adjuvant therapy.

PMID- 11309342
TI  - Angiopoietin-1 is inversely related to thymidine phosphorylase expression in
      human breast cancer, indicating a role in vascular remodeling.
AB  - PURPOSE: Angiogenesis is essential for tumor growth and metastasis. It is a
      complex, dynamic process that is coordinated by several classes of angiogenic
      factors. One candidate family is the Tie2 tyrosine kinase, whose expression is
      restricted largely to endothelial cells. Tie2 has three known ligands,
      angiopoietin (Ang)-1, Ang-2, and Ang-4, that have different functional effects
      but play a requisite role in embryonic vessel remodeling. Because there are only
      limited data on the Tie2 pathway in human breast cancer, and our previous data
      have suggested that breast tumors establish a blood supply by vascular
      remodeling, we have investigated the expression of Ang-1, Ang-2, Ang-4, and Tie2
      in a series of normal and neoplastic human breast tissues. EXPERIMENTAL DESIGN:
      We examined mRNA expression by reverse transcription-PCR in 6 normal and 52
      malignant breast tissues and correlated expression with clinicopathological and
      angiogenic variables. We also examined the effect of physiological levels of
      estrogen on Ang expression. RESULTS: Ang-1, Ang-2, Ang-4, and Tie2 were detected
      in 19%, 52%, 35%, and 65%, respectively, of tumor samples. There was a
      significant reduction in expression of tumor Ang-1 (P = 0.04), Ang-2 (P = 0.01),
      Ang-4 (P = 0.004), and Tie2 (P = 0.02) compared with that in normal breast
      tissues. There was a significant relationship in tumors between all Angs and
      between each ligand and Tie2. In a multivariate analysis, there were significant
      positive correlations between Ang-4 and estrogen receptor (P = 0.016) and a
      significant inverse correlation between Ang-1 and thymidine phosphorylase
      expression (P = 0.01). No significant associations were observed between the
      other members of the Ang/Tie2 gene family and patient age, tumor size, lymph node
      status, tumor grade, vascular invasion, tumor vascularity, vascular maturation,
      thymidine phosphorylase, or vascular endothelial growth factor A expression (P >
      0.05 for all). The potential regulation of Ang-4 by estrogen was further
      investigated in vitro. Addition of physiological concentrations of 17beta
      estradiol (1 nM) to hormone-free media caused no significant change in Ang-4 mRNA
      abundance (P = 0.75) in the estrogen receptor-positive cell line MCF-7 after
      either 2 or 18 h, despite demonstrating induction for the estrogen response gene
      pS2. CONCLUSIONS: These findings suggest that the Ang/Tie2 pathway plays a
      significant role in human breast tumor angiogenesis but provide no initial
      evidence for direct regulation of the pathway by estrogen.

PMID- 11309343
TI  - Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts
      metastasis-free survival in advanced carcinoma of the cervix.
AB  - Hypoxic tumors are known to be more malignant, to be more likely to metastasize,
      and to have a poor prognosis. They are also radio- and chemoresistant. For this
      reason, it is desirable that a clinically useful marker of hypoxia is found, so
      that treatment with radiotherapy and bioreductive chemotherapy can be rationally
      applied to individual patients. Glut-1 is a facilitative glucose transporter that
      is ubiquitously expressed in normal tissue and expressed at higher levels in a
      number of tumors. Its potential as an intrinsic hypoxia marker arises from its
      dual control in hypoxic conditions by reduced oxidative phosphorylation and the
      hypoxia-inducible factor (HIF-1) oxygen-sensing pathway. Eppendorf histography,
      by virtue of its proven predictive qualities, is a suitable gold standard used in
      our laboratory to validate new hypoxia markers. Using this technique,
      pretreatment pO(2) measurements were performed on 54 patients with locally
      advanced cervical carcinoma. Then, immunohistochemical staining was used to
      detect Glut-1 protein in individual tumor biopsy sections. Both measurements were
      made before initiation of treatment. By using a low-tech scoring system, pO(2)
      was found to correlate weakly with Glut-1 score (r = 0.28; P = 0.04). To
      extrapolate this correlation to the known adverse effects of tumor hypoxia on
      outcome, we examined the prognostic significance of Glut-1 staining in a
      retrospective series of 121 patients. An absence of Glut-1 significantly
      increased the likelihood of metastasis-free survival (P = 0.022) but did not
      significantly effect disease-free or recurrence-free survival. These findings
      suggest that Glut-1 be an intrinsic marker of hypoxia that can easily be applied
      in a clinical setting.

PMID- 11309344
TI  - Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to
      camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918.
AB  - This study was aimed at characterizing the role of BCRP/MXR/ABCP (BCRP) in
      resistance of the human ovarian tumor cell lines T8 and MX3 to camptothecins more
      extensively and investigating whether resistance can be reversed by inhibiting
      BCRP by GF120918. Camptothecins studied were topotecan, CPT-11, and its active
      metabolite SN-38, 9-aminocamptothecin, and the novel experimental camptothecins
      NX211, DX8951f, and BNP1350. Notably, DX8951f and BNP1350 appeared to be very
      poor substrates for BCRP, with much lower resistance factors observed both in T8
      and MX3 cells than observed for the other camptothecins tested. In the presence
      of a nontoxic dose level of GF120918, the intracellular accumulation of topotecan
      in the T8 and MX3 cells was completely restored to the intracellular levels
      observed in the sensitive IGROV1 parental cell line. This resulted in almost
      complete reversal of drug resistance to topotecan and to most of the other
      topoisomerase I drugs tested in the T8 cell line and to complete reversal in the
      MX3 cells. However, coincubation of DX8951f or BNP1350 with GF120918 did not
      affect the cytotoxicity of either of these drugs significantly. From the combined
      data, we conclude that the affinities of topoisomerase I drugs for BCRP are, in
      decreasing order: SN-38 > topotecan > 9-aminocamptothecin approximately CPT-11 >
      NX211 > DX8951f > BNP1350. Furthermore, GF120918 appears to be a potent reversal
      agent of BCRP-mediated resistance to camptothecins, with almost complete reversal
      noted at 100 nM. Potential BCRP-mediated resistance to topoisomerase I inhibitors
      can also be avoided by using the BCRP-insensitive drugs DX8951f or BNP1350. This
      observation may have important clinical implications for future development of
      novel camptothecins.

PMID- 11309345
TI  - Folylpoly-gamma-glutamate synthetase gene mRNA splice variants and protein
      expression in primary human leukemia cells, cell lines, and normal human tissues.
AB  - Folypoly-gamma-glutamate synthetase (FPGS) is essential for the cytotoxicity of
      "classical" antifolates and their efficacy in cancer chemotherapy. The expression
      of the FPGS gene appears controlled by both tissue/lineage-specific and
      proliferation-dependent mechanisms. Four alternative exon 1 splice variants of
      the FPGS gene have been described previously, but their significance in gene
      regulation has not been determined. Furthermore, alternative splicing of the
      human FPGS gene in normal or transformed cells in vivo has not been reported. We
      have examined the mRNA expression of these FPGS splice variants in primary human
      leukemia cells, cell lines, and normal human hematopoietic progenitors using
      reverse transcription-PCR. Specific primers were designed to amplify splice
      variants 1, 1A, 1B, and 1C; and full-length FPGS mRNA was amplified using primers
      for exons 14 and 15 at the 3' end of the gene. In this study, we demonstrate that
      all four alternative exon 1 variants are expressed in all primary leukemia cells
      and cell lines (ALL and AML), as well as in normal human hematopoietic
      progenitors. No significant differences in mRNA expression were detected in
      primary cells or cell lines for the four exon 1 splice variants. Normal
      circulating human lymphocytes (peripheral blood mononuclear cells) also expressed
      mRNA amplified from full-length FPGS and the four exon 1 splice variants,
      although no detectable FPGS activity was found. Using Western immunoblotting, we
      show that FPGS protein is expressed in these peripheral blood mononuclear cells;
      thus, we propose that posttranslational modification(s) is required for
      expression of a functional FPGS protein in human lymphohematopoietic cells. In
      addition, poly(A)(+) RNA from normal human adult and fetal tissues and leukemia
      cell lines was analyzed by Northern blot methodology. Total FPGS mRNA expression
      showed tissue-specificity, and higher levels were observed in human fetal tissues
      compared with adult tissues. The data presented herein demonstrate the existence
      of these FPGS mRNA splice variants in normal and transformed human hematopoietic
      cells and indicate that alternative splicing of the 5' end of the human FPGS gene
      does occur in primary cells in vivo. However, its role in regulating the
      expression of its mRNA remains to be determined.

PMID- 11309346
TI  - Effective particle-mediated vaccination against mouse melanoma by
      coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony
      stimulating factor.
AB  - Particle-mediated gene delivery was used to immunize mice against melanoma. Mice
      were immunized with a plasmid cDNA coding for the human melanoma-associated
      antigen, gp100. Murine B16 melanoma, stably transfected with human gp100
      expression plasmid, was used as a tumor model. Particle-mediated delivery of
      gp100 plasmid into the skin of naive mice resulted in significant protection from
      a subsequent tumor challenge. Co-delivery of murine granulocyte-macrophage colony
      stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid
      consistently resulted in a greater level of protection from tumor challenge. The
      inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in
      the gp100 plasmid dose required for antitumor efficacy. Protection from tumor
      challenge was achieved with as little as 62.5 ng of gp100 DNA per vaccination.
      Tumor protection induced by the gp100 + GM-CSF gene combination was T cell
      mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and
      anti-CD8 monoclonal antibodies. In addition, administration of the gp100 + GM-CSF
      DNA vaccine to mice bearing established 7-day tumors resulted in significant
      suppression of tumor growth. These results indicate that inclusion of GM-CSF DNA
      augments the efficacy of particle-mediated vaccination with gp100 DNA, and this
      form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in
      melanoma patients.

PMID- 11309347
TI  - Inhibition of transformed cell growth and induction of cellular differentiation
      by pyroxamide, an inhibitor of histone deacetylase.
AB  - PURPOSE: We have synthesized a series of hybrid polar compounds that induce
      differentiation and/or apoptosis of various transformed cells. These agents are
      also potent inhibitors of histone deacetylases (HDACs). Pyroxamide (suberoyl-3
      aminopyridineamide hydroxamic acid) is a new member of this class of compounds
      that is currently under development as an anticancer agent. We investigated the
      activity of pyroxamide as an inducer of differentiation and/or apoptosis in
      transformed cells. EXPERIMENTAL DESIGN AND RESULTS: Pyroxamide, at micromolar
      concentrations, induced terminal differentiation in murine erythroleukemia (MEL)
      cells and caused growth inhibition by cell cycle arrest and/or apoptosis in MEL,
      prostate carcinoma, bladder carcinoma, and neuroblastoma cells. Administration of
      pyroxamide (100 or 200 mg/kg/day) to nude mice at doses that caused little
      evident toxicity significantly suppressed the growth of s.c. CWR22 prostate
      cancer xenografts. Despite the potent growth-inhibitory effects of pyroxamide in
      this tumor model, serum prostate-specific antigen levels in control versus
      pyroxamide-treated mice were not significantly different. Pyroxamide is a potent
      inhibitor of affinity-purified HDAC1 (ID(50) = 100 nM) and causes the
      accumulation of acetylated core histones in MEL cells cultured with the agent.
      Human CWR22 prostate tumor xenografts from mice treated with pyroxamide (100 or
      200 mg/kg/day) showed increased levels of histone acetylation and increased
      expression of the cell cycle regulator p21/WAF1, compared with tumors from
      vehicle-treated control animals. CONCLUSIONS: The findings suggest that
      pyroxamide may be a useful agent for the treatment of malignancy and that
      induction of p21/WAF1 in transformed cells by pyroxamide may contribute to the
      antitumor effects of this agent.

PMID- 11309348
TI  - Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity
      against breast cancer in vivo.
AB  - PURPOSE: Trichostatin A (TSA), an antifungal antibiotic with cytostatic and
      differentiating properties in mammalian cell culture, is a potent and specific
      inhibitor of histone deacetylase (HDAC) activity. The purpose of this study was
      to evaluate the antiproliferative and HDAC inhibitory activity of TSA in vitro in
      human breast cancer cell lines and to assess its antitumor efficacy and toxicity
      in vivo in a carcinogen-induced rat mammary cancer model. EXPERIMENTAL DESIGN AND
      RESULTS: TSA inhibited proliferation of eight breast carcinoma cell lines with
      mean +/- SD IC(50) of 124.4 +/- 120.4 nM (range, 26.4-308.1 nM). HDAC inhibitory
      activity of TSA was similar in all cell lines with mean +/- SD IC(50) of 2.4 +/-
      0.5 nM (range, 1.5-2.9 nM), and TSA treatment resulted in pronounced histone H4
      hyperacetylation. In randomized controlled efficacy studies using the N-methyl-N
      nitrosourea carcinogen-induced rat mammary carcinoma model, TSA had pronounced
      antitumor activity in vivo when administered to 16 animals at a dose of 500
      microg/kg by s.c. injection daily for 4 weeks compared with 14 control animals.
      Furthermore, TSA did not cause any measurable toxicity in doses of up to 5 mg/kg
      by s.c. injection. Forty-one tumors from 26 animals were examined by histology.
      Six tumors from 3 rats treated with TSA and 14 tumors from 9 control animals were
      adenocarcinomas. In contrast, 19 tumors from 12 TSA-treated rats had a benign
      phenotype, either fibroadenoma or tubular adenoma, suggesting that the antitumor
      activity of TSA may be attributable to induction of differentiation. Two control
      rats each had tumors with benign histology. CONCLUSIONS: The present studies
      confirm the potent dose-dependent antitumor activity of TSA against breast cancer
      in vitro and in vivo, strongly supporting HDAC as a molecular target for
      anticancer therapy in breast cancer.

PMID- 11309349
TI  - The angiogenesis inhibitor tnp-470 effectively inhibits human neuroblastoma
      xenograft growth, especially in the setting of subclinical disease.
AB  - Tumor vascularity is highly correlated with disease outcome in neuroblastoma.
      Thus, novel therapeutics that target the vascular endothelium are candidates for
      incorporation into clinical trials. We therefore examined the effect of TNP-470
      on human neuroblastoma growth in mouse models reflecting both clinically evident
      and minimal disease. Mice were inoculated s.c. or by tail vein injection with
      10(7) human neuroblastoma-derived CHP-134 cells and treated with TNP-470 (100
      mg/kg/dose s.c. three times a week or by continuous infusion) or saline.
      Treatment was given as a single agent in established xenografts, 10 days after
      450 mg/kg of cyclophosphamide, or 12 h after tumor inoculation. Tumor growth rate
      was markedly inhibited in mice receiving TNP-470 administered alone both s.c. and
      by continuous infusion with a treatment to control ratio (T:C) at day 16 of 0.3
      (P < 0.001) and a T:C at day 30 of 0.4 (P = 0.029) for each dosing method,
      respectively. TNP-470 also significantly inhibited tumor growth when administered
      following cyclophosphamide (T:C at day 30 = 0.2, P < 0.001) and inhibited disease
      establishment when given shortly after xenograft inoculation (T:C at day 30 =
      0.1, P < 0.001) or tail vein injection. TNP-470 was shown to directly inhibit
      angiogenesis by Matrigel assay (P =.010) and to increase the apoptotic index in
      treated tumors. These data show that TNP-470 is a potent inhibitor of human
      neuroblastoma growth rate and tumorigenicity. We speculate that TNP-470 may be a
      useful adjuvant therapy for high-risk neuroblastoma patients, particularly when
      used in settings of minimal disease status.

PMID- 11309350
TI  - Efficacy of local versus systemic application of antibody-cytokine fusion
      proteins in tumor therapy.
AB  - Application of immunocytokines [fusion proteins (FuPs)] where the cytokine has
      been coupled to an antibody may not produce the severe side effects frequently
      observed during systemic application of cytokines in cancer therapy. However, it
      has not been explored whether FuPs are sufficient for intratumoral activation of
      leukocytes or whether intratumoral versus systemic application may be of greater
      efficacy. Interleukin 2 (IL2) or tumor necrosis factor (TNF) coupled to an anti
      epidermal growth factor receptor monoclonal antibody (IL2-FuP or TNF-FuP) were
      tested in SCID mice bearing a human epidermal growth factor receptor-positive
      melanoma transplant and being reconstituted with human HLA-matched peripheral
      blood leukocytes. Whole-body autoradiography revealed larger accumulation and
      prolonged retention of i.v. or intratumorally applied IL2-FuP or TNF-FuP compared
      with the antibody. Even with low doses of FuP, tumor growth was significantly
      retarded, with the survival time being further prolonged by the intratumoral
      application. Furthermore, outgrowth of the tumor was prevented in approximately
      50% of mice as long as they received weekly injections of peripheral blood
      leukocytes concomitantly with the FuPs, which confirmed that it was the donor
      leukocytes activated in vivo that retarded tumor growth. An in vitro analysis
      revealed that the IL2-FuP supported mainly proliferation and lymphokine-activated
      killer cell activity, whereas TNF-FuP stimulated cytokine production and
      cytotoxic activity of monocytes and, to a low degree, of T cells. Both TNF-FuP
      and IL2-FuP significantly accumulated in the tumor, which led to retardation of
      tumor growth. The therapeutic effect was improved by intratumoral application.
      Importantly, the efficacy of both IL2-FuP and TNF-FuP depended on the induction
      of an immune response in vivo.

PMID- 11309351
TI  - Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase
      profiles of cell lines of the National Cancer Institute's Anticancer Drug Screen.
AB  - PURPOSE: To determine the expression of three targets of 5-fluorouracil (5-FU)
      and 5-fluoro-2'-deoxyuridine (FdUrd) in human tumor cell lines and to compare
      these with the 50% growth inhibition concentrations (GI(50)) from the National
      Cancer Institute database. EXPERIMENTAL DESIGN: Thymidine kinase (TK) activity
      was assessed by conversion of [(3)H]thymidine to [(3)H]TMP. Thymidylate synthase
      (TS) protein expression was determined by Western analysis. TS and
      dihydropyrimidine dehydrogenase (DPD) mRNA expression were measured by
      quantitative reverse transcription-PCR. RESULTS: The median (range) for the
      targets were as follows: 5-FU GI(50), 20.8 microM (0.8-536); FdUrd GI(50), 0.75
      microM (0.25-237); TK, 0.93 nmol/min/mg (0.16-5.7); in arbitrary units: TS
      protein, 0.41 (0.05-2.95); TS mRNA, 1.05 (0.12-6.41); and DPD mRNA, 1.09 (0.00
      24.4). A moderately strong correlation was noted between 5-FU and FdUrd GI(50)s
      (r = 0.60), whereas a weak-moderate correlation was seen between TS mRNA and
      protein expression (r = 0.45). Neither TS expression nor TK activity correlated
      with 5-FU or FdUrd GI(50)s, whereas lines with lower DPD expression tended to be
      more sensitive to 5-FU. Cell lines with faster doubling times and wild-type p53
      were significantly more sensitive to 5-FU and FDURD: CONCLUSIONS: The lack of
      correlation may in part be attributable to the influence of downstream factors
      such as p53, the observation that the more sensitive cell lines with faster
      doubling times also had higher TS levels, and the standard procedure of the
      screen that uses a relatively short (48-h) drug exposure.

PMID- 11309352
TI  - Induction of apoptosis in colon cancer cells by cyclooxygenase-2 inhibitor NS398
      through a cytochrome c-dependent pathway.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown cancer preventive
      activity in patients who took them frequently. These drugs can induce tumor cells
      to undergo apoptosis in vitro. NS398, a cyclooxygenase-2 (COX-2)-selective
      inhibitor, has been reported to cause apoptosis in cancer cell lines. Therefore,
      we examined its effect on 15 human colon cancer cell lines and investigated its
      mechanism of action. NS398 decreased cell viability in all of the cell lines.
      Tumor cells that expressed COX-2 were shown to be more sensitive to NS398
      treatment. In three selected colon cancer cell lines, NS398-induced apoptosis was
      mediated by the release of cytochrome c from mitochondria and, consequently, by
      the activation of caspase-9 and caspase-3 and by the cleavage of poly(ADP-ribose)
      polymerase. In contrast, caspase-8 was not involved in NS398-induced apoptosis,
      which suggested that the cytochrome c pathway may play an important role in NS398
      induced apoptosis in colon cancer cell lines. Therefore, the combination of NS398
      with apoptosis-inducing drugs through cytochrome c-independent pathways may be
      warranted.

PMID- 11309353
TI  - Enhanced turnover of all-trans-retinoic acid and increased formation of polar
      metabolites in head and neck squamous cell carcinoma lines compared with normal
      oral keratinocytes.
AB  - Retinoids show promise in the treatment of various (pre)malignancies, including
      head and neck squamous cell carcinoma (HNSCC). Previous studies have shown that
      the metabolic pathways of retinoids are important in the anticancer effect of
      retinoids, and that these pathways may change during carcinogenesis. In the
      present study, we analyzed HNSCC cell lines (n = 11) and normal oral keratinocyte
      cultures (n = 11) by reverse-phase high-performance liquid chromatography and
      conducted growth inhibition assays. We demonstrate here that in contrast to
      normal oral keratinocytes, HNSCC cell lines: (a) had averaged a 17-fold greater
      turnover rate of all-trans-retinoic acid (RA); (b) had a 1.9-fold less RA-induced
      growth inhibition; (c) were able to form polar metabolites; and (d) were able to
      catabolize 4-oxo-RA. Furthermore, the mRNA expression of the RA-specific 4
      hydroxylase, CYP26A1, was dramatically increased after RA-induction in the two
      HNSCC cell lines with the highest metabolism, was undetectable in normal
      keratinocytes, and was not inducible by RA. Next, introduction of CYP26A1 cDNA in
      a low-metabolizing HNSCC cell line resulted in an 11-fold higher turnover rate of
      RA and a 12-fold increase in the amount of polar metabolites, but it did not
      change sensitivity to RA. These observations point to fundamental changes in RA
      metabolism pathways during HNSCC carcinogenesis and may provide clues to a more
      rational approach for RA-mediated intervention.

PMID- 11309354
TI  - Angiogenesis inhibitor TNP-470 during bone marrow transplant: safety in a
      preclinical model.
AB  - High-dose therapy with stem cell rescue is a treatment option for patients with
      advanced solid tumors. Although this approach has promise for some pediatric
      cancers, especially neuroblastoma, it is limited by the risk of relapse
      posttransplant as well as concern about possible reinfused tumor cells in
      autologous stem cell products. Antiangiogenic agents given during and after
      recovery from high-dose therapy with stem cell rescue may decrease the risk of
      relapse. TNP-470 is an antiangiogenic agent now in clinical trials. Although it
      inhibits the growth of bone marrow (BM) colony-forming cells in vitro, no
      significant hematological toxicity has been seen in Phase I trials. To assess the
      feasibility of using antiangiogenic agents during the period of posttransplant
      hematopoietic engraftment, we have developed a model of stem cell transplant in
      mice. Mice were lethally irradiated and then rescued with stem cells containing a
      transgene expressed in the hematopoietic lineage. Mice were then treated with TNP
      470 or placebo, and assessed for survival, successful engraftment, and kinetics
      of engraftment. Both treated and control mice demonstrated reliable multilineage
      engraftment as well as normal lymphoid maturation with no excess mortality in the
      treated group. WBCs were lower but still within the normal range at d+28 in mice
      treated with bolus TNP-470, but not in those treated with continuous infusion TNP
      470, compared with controls. These data indicate that inhibitors of angiogenesis
      do not adversely impact engraftment after stem cell transplantation.

PMID- 11309355
TI  - Detection of mitomycin C-DNA adducts in human breast cancer cells grown in
      culture, as xenografted tumors in nude mice, and in biopsies of human breast
      cancer patient tumors as determined by (32)P-postlabeling.
AB  - Mitomycin C (MMC) is a DNA cross-linking agent that has been used in cancer
      chemotherapy for >20 years. However, little is known either qualitatively or
      quantitatively about the relationship between formation and repair of specific
      MMC-DNA adducts and specific biological outcomes. The goal of this study was to
      examine formation and removal of specific MMC-DNA adducts in breast cancer cells
      using a (32)P-postlabeling assay in relation to cytotoxicity and other biological
      end points. MMC-DNA adducts were measured in cultured human metastatic MDA-MB-435
      cells, in the same cells xenografted as a mammary tumor in nude mice, and in
      metastatic tumor biopsies obtained from human breast cancer patients undergoing
      MMC-based therapy. MMC adducts corresponding to the CpG interstrand cross-link,
      the MMC-G bifunctional monoadduct, and two isomers of the MMC-G monofunctional
      monoadduct were detected in most samples. Despite similarities in the overall
      patterns of adduct formation, there were substantial differences between the
      cultured cells and the in vivo tumors in their adduct distribution profile,
      kinetics of adduct formation and removal, and relationship of specific adduct
      levels to cytotoxicity, suggesting that the in vivo microenvironment (e.g.,
      degree of oxygenation, pH, activity of oxidoreductases, and other factors) of
      breast cancer cells may significantly modulate these parameters.

PMID- 11309356
TI  - Calcitriol (1,25-dihydroxycholecalciferol) enhances paclitaxel antitumor activity
      in vitro and in vivo and accelerates paclitaxel-induced apoptosis.
AB  - We demonstrated that calcitriol has antiproliferative activity in squamous cell
      carcinoma and prostatic adenocarcinoma and enhances the antitumor activity of
      platinum-based agents. In this study, we examined whether calcitriol also
      increases paclitaxel cytotoxicity. The effect of treatment on growth of the
      murine squamous cell carcinoma (SCCVII/SF) and human prostatic adenocarcinoma (PC
      3) was determined by clonogenic assay, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, and monitoring tumor growth. Treatment of SCC
      or PC-3 cells in vitro with calcitriol prior to paclitaxel significantly reduced
      clonogenic survival compared with either agent alone. Median-dose effect analysis
      revealed that calcitriol and paclitaxel interact synergistically. Treatment of
      SCC or PC-3 tumor-bearing mice with calcitriol prior to paclitaxel resulted in
      substantially greater growth inhibition than was achieved with either agent
      alone, supporting the combined use of calcitriol and paclitaxel in the treatment
      of solid tumors. To explore the molecular basis for the enhanced antitumor
      activity of this combination, the effect of treatment on p21(Waf-1) (p21), Bcl-2,
      and poly(ADP-ribose) polymerase expression was evaluated in PC-3. A 72-h
      pretreatment with calcitriol reduced p21 expression and increased paclitaxel
      cytotoxicity (measured after 24 h) without evidence of apoptosis [poly(ADP
      ribose) polymerase cleavage]. After 48 h, paclitaxel induced apoptosis, the
      extent of which was increased similarly by pretreatment or concurrent treatment
      with calcitriol. We therefore propose a model for calcitriol enhancement of
      paclitaxel cytotoxicity in which the "early" (24 h) effects are schedule
      dependent and not attributed to enhancement of paclitaxel-induced apoptosis. In
      contrast, the "delayed" (48-h) enhancement of paclitaxel activity by calcitriol
      is schedule independent and associated with acceleration of apoptosis.

PMID- 11309357
TI  - Combretastatin A4 prodrug study of effect on the growth and the microvasculature
      of colorectal liver metastases in a murine model.
AB  - Combretastatin A4P (CA4P) is a prodrug that, in active form, binds to tubulin
      microtubules of capillary endothelial cells. Studies to date indicate it has
      significant activity as a specific tumor vascular targeting agent. The goals were
      to assess the effects of CA4P on tumor growth and microvasculature of colorectal
      liver metastases in the mouse model, using stereological and histological methods
      to measure tumor growth, and vascular corrosion casting and laser doppler
      flowmetry to assess effect on the microvasculature. Continuous s.c. infusion of
      CA4P produced a major reduction in tumor growth. The percentage of the liver
      occupied by metastases decreased from 20.55 +/- 13.3% in controls to 7.46 +/-
      5.99% in treated animals (P = 0.03). Ultrastructural study of tumor
      microvasculature after a single dose of CA4P revealed marked effects 1 h after
      treatment. There was loss of patent microvessels at the normal liver-tumor
      interface. Central microvascular density was reduced, with constriction and
      tapering of vessels. CA4P appeared to cause no damage to normal liver tissue or
      vasculature. Tumor blood flow decreased from 37.6 +/- 13.9% in controls to 24.4
      +/- 6.1% in tumors >5 mm in diameter, 1 h after treatment with CA4P (P < 0.03).
      Quantitative histology of tissue at 6 and 24 h after CA4P treatment showed a
      significant increase in tumor necrosis (48.7 +/- 21% and 55.5 +/- 19% compared
      with controls, 20.6 +/- 8%; P = 0.01). Continuous infusion with CA4P causes
      marked reduction in tumor volume. A single dose of CA4P causes major changes of
      the tumor microvasculature, reduction of tumor blood flow, and increase in tumor
      necrosis. CA4P has a potential role in the management of patients with liver
      metastases.

PMID- 11309358
TI  - Biodistribution properties of (111)indium-labeled C-functionalized trans
      cyclohexyl diethylenetriaminepentaacetic acid humanized 3S193 diabody and
      F(ab')(2) constructs in a breast carcinoma xenograft model.
AB  - The humanized complementarity determining region-grafted anti-Lewis Y (Le(y))
      monoclonal antibody [humanized 3S193 (hu3S193)] was developed for targeting Le(y)
      expressing epithelial tumors such as breast, colon, lung, prostate, and ovarian
      carcinoma. We are exploring the potential use of smaller molecular size, bivalent
      analogues of hu3S193, because the faster blood clearance of M(r) approximately
      54,000 diabody and M(r) approximately 110,000 F(ab')(2) molecules may be
      advantageous in achieving optimal and rapid tumor uptake for diagnostic and
      potential therapeutic applications. The single-chain variable fragment-5 residue
      linker construct (diabody) was expressed using the bacterial secretion vector
      pPOW3, and soluble product was purified without refolding processes. The
      F(ab')(2) fragment was obtained by pepsin digest of parental hu3S193. To
      facilitate evaluations, the radiometal (111)In was used to label C-functionalized
      trans-cyclohexyl diethylenetriaminepentaacetic acid chelated diabody and
      F(ab')(2). The immunoreactivity of the radiolabeled constructs was 41.3 and
      58.6%, and the K(a) was 1.68 x 10(6) M(-1) and 5.33 x 10(6) M(-1) for the diabody
      and F(ab')(2), respectively. Radioconjugates were injected into mice bearing
      Le(y)-positive MCF-7 tumors, and biodistribution properties were determined at
      various time points after injection. The uptake of radiolabeled diabody in
      xenografts was maximal at 1 h after injection (4.7 +/- 0.6% injected dose/g),
      whereas the F(ab')(2) peaked at 8 h after injection (14.2 +/- 2.4% injected
      dose/g). The tumor:blood ratio at 4 h for the diabody and F(ab')(2) was 5:1 and
      2:1, which increased to 20:1 and 5:1, respectively, at 8 h and increased further
      to 40:1 and 130:1, respectively, at 48 h. These results demonstrate that the
      diabody construct may have applications as a diagnostic imaging reagent, whereas
      F(ab')(2) displayed effective tumor targeting and may have potential as a
      therapeutic molecule in patients with Le(y)-expressing tumors.

PMID- 11309359
TI  - The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth
      and angiogenesis: possible role of the vascular endothelial growth factor.
AB  - Angiotensin-I converting enzyme (ACE) inhibitor is used widely as an
      antihypertensive agent, and it has been suggested recently that it decreases the
      risk of cancer (A. F. Lever et al., Lancet, 352: 179-184, 1998). In this study,
      we examined the effect of several ACE inhibitors and angiotensin-II type 1
      receptor (AT(1)-R) antagonists on tumor development and angiogenesis in a murine
      hepatocellular carcinoma model. Among ACE inhibitors, perindopril appeared to be
      a potent inhibitor of tumor development and angiogenesis, whereas AT(1)-R
      antagonists did not exert such an inhibitory effect. The inhibitory effect of
      perindopril was achieved even on established tumors. The level of the potent
      angiogenic factor, vascular endothelial growth factor (VEGF), in the tumor was
      significantly suppressed by perindopril. In vitro studies showed that perindopril
      derived active form, perindoprilat, suppressed the endothelial cell tubule
      formation. Perindoprilat treatment also significantly inhibited VEGF mRNA
      expression in BNL-HCC cells in vitro. These results showed that the ACE inhibitor
      perindopril inhibited tumor development and angiogenesis independent from AT(1)-R
      blockage, and that VEGF alternation may be involved in the mechanism of this
      inhibitory effect. Because perindopril is widely used in clinical practice, it
      may represent an effective new strategy for anticancer therapy.

PMID- 11309360
TI  - Schedule dependency of antitumor activity in combination therapy with
      capecitabine/5'-deoxy-5-fluorouridine and docetaxel in breast cancer models.
AB  - Docetaxel and capecitabine are being prescribed for the treatment of breast
      cancer. In this study, we tried to identify the optimal administration schedule
      in combination therapy with these anticancer drugs in human cancer xenograft
      models. Capecitabine was given p.o. daily for 2 weeks (days 1-14), whereas
      docetaxel was given i.v. on day 1, day 8, or day 15 in a 3-week regimen to the
      mice bearing MX-1 human breast cancer xenograft. The combination showed better
      antitumor efficacy than the monotherapy of either agent in either dosing regimen.
      However, the most potent and synergistic activity was observed when docetaxel was
      given on day 8. This potent effect appears to be characteristic of the
      combination of docetaxel with capecitabine or its intermediate metabolite 5'
      deoxy-5-fluorouridine (doxifluridine; 5'-dFUrd). Docetaxel given on day 8 showed
      a potent effect in combination with 5'-dFUrd, but a much weaker effect was
      observed in combination with 5-fluorouracil or UFT, a fixed combination of
      tegafur and uracil. Better efficacy was also observed in the MAXF401 human breast
      cancer xenograft and in the mouse A755 mammary tumor when docetaxel was given at
      the middle of the capecitabine or 5'-dFUrd treatment rather than other dosing
      regimens. In contrast, the efficacy in WiDr human colon cancer xenograft was
      somewhat better when docetaxel was given on day 1. One possible explanation for
      the synergy is that docetaxel up-regulates tumor levels of thymidine
      phosphorylase, the enzyme essential for the activation of capecitabine and 5'
      dFUrd to 5-fluorouracil. In fact, docetaxel up-regulated the thymidine
      phosphorylase levels 4.8- and 1.9-fold in the WiDr and MX-1 models, respectively.
      However, it did not significantly up-regulate in the MAXF401 and A755 models in
      which a potent combination effect was observed as well. Other mechanisms,
      particularly those for the synergy with docetaxel given at the middle during
      capecitabine/5'-dFUrd administration, would also exist. Based on these
      observations, clinical studies on the day 8 combination regimen with docetaxel
      and capecitabine/5'-dFUrd are warranted.

PMID- 11309361
TI  - Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene
      transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer
      cell lines.
AB  - The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an
      important role in the proteolytic cascade involved in the metastasis of lung and
      other cancers. We report that the reduction in uPAR levels produced by an
      antisense strategy using an adenovirus construct (Ad-uPAR) in H1299 cells, an
      invasive human lung cancer cell line that produces high levels of uPAR, resulted
      in a decrease of uPAR levels to 80-90% of those seen in cells infected with mock
      or adenovirus (Ad)-cytomegalovirus vector controls. In addition, increasing the
      multiplicity of infection from 25 to 200 caused a corresponding decrease in the
      level of uPAR protein within 5 days of treatment, as shown by Western blot
      analysis. Furthermore, the in vitro translation of total RNA levels of Ad-uPAR
      infected H1299 cells in a rabbit reticulocyte lysate system caused a 50-70%
      decrease in uPAR immunoprecipitate in Ad-uPAR-infected cells relative to the
      levels in cells of mock and vector controls. The Matrigel invasion assay showed
      the invasion of H1299 cells and A549 cells infected with Ad-uPAR to be decreased
      by 70% relative to mock- and vector-infected controls. Infection of tumor cells
      with Ad-uPAR before implantation significantly reduced the incidence of lung
      metastasis by 85% as compared with the control virus-infected cells injected into
      nude mice through the tail vein. Our collective results show that the uPAR system
      is a potential target of treatment for lung cancers.

PMID- 11309362
TI  - Bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(I.V.) as a novel
      antileukemic agent with matrix metalloproteinase inhibitory activity.
AB  - We have examined the in vitro anticancer activity of METVAN [bis(4,7-dimethyl
      1,10 phenanthroline) sulfatooxovanadium(IV); VO(SO(4))(Me(2)-Phen)(2)] against
      acute lymphoblastic leukemia (ALL; NALM-6 and MOLT-3), acute myeloid leukemia
      (AML; HL-60), Hodgkin's disease (HS445), and multiple myeloma (ARH-77, U266BL,
      and HS-SULTAN) cell lines as well as primary leukemic cells from patients with
      ALL, AML, and chronic acute myeloid leukemia (CML). METVAN induced apoptosis in
      NALM-6, MOLT-3, and HL-60 cells in a concentration-dependent fashion with EC(50)
      values of 0.19 +/- 0.03 microM, 0.19 +/- 0.01 microM, and 1.1 +/- 0.2 microM,
      respectively. METVAN induced apoptosis at low micromolar concentrations in
      primary leukemic cells from patients with ALL, AML, and CML. METVAN inhibited the
      constitutive expression of matrix metalloproteinase (MMP)-9 protein and its
      gelatinolytic activity in HL-60 cells and MMP-2 as well as MMP-9 gelatinolytic
      activities in leukemic cells from ALL, AML, and CML patients. Furthermore, METVAN
      inhibited the leukemic cell adhesion to the extracellular matrix proteins
      laminin, type IV collagen, vitronectin, and fibronectin and the invasion through
      Matrigel matrix. Further preclinical development of METVAN may provide the basis
      for the development of more effective chemotherapy programs.

PMID- 11309363
TI  - The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific
      methylation patterns in normal and tumor cells.
AB  - The 5' region for the endothelin receptor B (EDNRB) gene is a complex CpG island
      giving rise to four individual transcripts initiating within the island. Here,
      for the first time, we analyze the relationship between methylation and gene
      expression in a CpG island located in the 5' region of a gene with multiple
      transcription start sites. The CpG island was unmethylated in normal prostate and
      bladder tissue, whereas it became methylated in apparently normal colonic
      epithelium. Tumors derived from these tissues were frequently hypermethylated
      relative to the respective normal tissues. Analysis of 11 individual CpG sites
      located throughout the CpG island showed that specific sites with high
      methylation levels in several tumors were also methylated in normal tissues,
      suggesting that they might serve as foci for further de novo methylation. This
      region also had high levels of methylation in several cancer cell lines, and we
      found that a low methylation level in a small region within the 5' region
      correlated with expression of the 5'-most transcript. Interestingly, almost
      complete methylation 200-1000 bp downstream of the transcriptional start site did
      not block expression of this transcript. Finally, we show that treatment with 5
      aza-2'-deoxycytidine can induce transcriptional activation of the four EDNRB
      transcripts. Our results show the existence of differential, tissue-dependent
      methylation at the EDNRB 5' region, suggest the existence of a spreading
      mechanism for de novo methylation, starting from methylation hotspots, and show
      that hypermethylation immediately 3' to a transcriptional start site does not
      prevent initiation.

PMID- 11309364
TI  - Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain
      function.
AB  - PAX6 is essential for ocular morphogenesis. Mutations in the PAX6 gene produce
      various phenotypes, including aniridia, Peters' anomaly, foveal hypoplasia,
      autosomal dominant keratitis and congenital cataracts. PAX6 functions as a
      transcription factor and has two DNA binding domains (a paired domain and a
      homeodomain) which are joined by a linker, and a transactivation domain enriched
      in proline, serine and threonine (PST) at the C-terminus. The mechanism of PAX6
      function is not clearly understood, and few target genes in vertebrates have been
      identified. We examined disease-causing missense mutations in the PST domain to
      understand how they affect the function of PAX6. Upon examining the DNA samples
      of aniridia patients, we identified three missense mutations in the PST domain:
      P375Q (a novel mutation) and the previously reported Q422R and X423L mutations.
      On the basis of functional analysis, the P375Q mutant appears to have a normal
      transactivation activity but lower DNA binding through the paired domain than the
      wild-type. The Q422R mutation resulted in the loss of DNA binding ability of the
      PAX6 homeodomain. Substitution analyses of the C-terminal amino acid (codon 422)
      indicated that an amino acid at codon 422 is required for DNA binding of the
      homeodomain of intact PAX6 and that the polarity and charge of the side-chain of
      the terminal amino acid influence this binding.

PMID- 11309365
TI  - Inducible expression of mutant alpha-synuclein decreases proteasome activity and
      increases sensitivity to mitochondria-dependent apoptosis.
AB  - Parkinson's disease (PD) is a common progressive neurodegenerative disorder
      caused by the loss of dopaminergic neurons in the substantia nigra. Although
      mutations in alpha-synuclein have been identified in autosomal dominant PD, the
      mechanism by which dopaminergic neural cell death occurs remains unknown.
      Proteins encoded by two other genes in which mutations cause familial PD, parkin
      and UCH-L1, are involved in regulation of the ubiquitin-proteasome pathway,
      suggesting that dysregulation of the ubiquitin-proteasome pathway is involved in
      the mechanism by which these mutations cause PD. We established inducible PC12
      cell lines in which wild-type or mutant alpha-synuclein can be de-repressed by
      removing doxycycline. Differentiated PC12 cell lines expressing mutant alpha
      synuclein showed decreased activity of proteasomes without direct toxicity. Cells
      expressing mutant alpha-synuclein showed increased sensitivity to apoptotic cell
      death when treated with sub-toxic concentrations of an exogenous proteasome
      inhibitor. Apoptosis was accompanied by mitochondrial depolarization and
      elevation of caspase-3 and -9, and was blocked by cyclosporin A. These data
      suggest that expression of mutant alpha-synuclein results in sensitivity to
      impairment of proteasome activity, leading to mitochondrial abnormalities and
      neuronal cell death.

PMID- 11309366
TI  - A novel mutation in the coding region of the prosaposin gene leads to a complete
      deficiency of prosaposin and saposins, and is associated with a complex
      sphingolipidosis dominated by lactosylceramide accumulation.
AB  - A fatal infantile storage disorder with hepatosplenomegaly and severe
      neurological disease is described. Sphingolipids, including monohexosylceramides
      (mainly glucosylceramide), dihexosylceramides (mainly lactosylceramide),
      globotriaosyl ceramide, sulphatides, ceramides and globotetraosyl ceramide, were
      stored in the tissues. In general, cholesterol and sphingomyelin levels were
      unaltered. The storage process was generalized and affected a number of cell
      types, with histiocytes, which infiltrated a number of visceral organs and the
      brain, especially involved. The ultrastructure of the storage lysosomes was
      membranous with oligolamellar, mainly vesicular, profiles. Infrequently, there
      were Gaucher-like lysosomes in histiocytes. The neuropathology was severe and
      featured neuronal storage and loss with a massive depopulation of cortical
      neurons and pronounced fibrillary astrocytosis. There was a paucity of myelin and
      stainable axons in the white matter with signs of active demyelination.
      Immunohistochemical investigations indicated that saposins A, B, C and D were all
      deficient. The patient was homozygous for a 1 bp deletion (c.803delG) within the
      SAP-B domain of the prosaposin gene which leads to a frameshift and premature
      stop codon. In the heterozygous parents, mutant cDNA was detected by
      amplification refractory mutation analysis in the nuclear, but not the
      cytoplasmic, fraction of fibroblast RNA, indicating that the mutant mRNA was
      rapidly degraded. The storage process in the proband resembled that of a
      published case from an unrelated family. Saposins were also deficient in this
      case, leading to its reclassification as prosaposin deficiency, and her mother
      was found to be a carrier for the same c.803delG mutation. Both of the
      investigated families came from the same district of eastern Slovakia.

PMID- 11309367
TI  - MECP2 is highly mutated in X-linked mental retardation.
AB  - Following the recent discovery that the methyl-CpG binding protein 2 (MECP2) gene
      located on Xq28 is involved in Rett syndrome (RTT), a wild spectrum of
      phenotypes, including mental handicap, has been shown to be associated with
      mutations in MECP2. These findings, with the compelling genetic evidence
      suggesting the presence in Xq28 of additional genes besides RabGDI1 and FMR2
      involved in non-specific X-linked mental retardation (MRX), prompted us to
      investigate MECP2 in MRX families. Two novel mutations, not found in RTT, were
      identified. The first mutation, an E137G, was identified in the MRX16 family, and
      the second, R167W, was identified in a new mental retardation (MR) family shown
      to be linked to Xq28. In view of these data, we screened MECP2 in a cohort of 185
      patients found negative for the expansions across the FRAXA CGG repeat and
      reported the identification of mutations in four sporadic cases of MR. One of the
      mutations, A140V, which we found in two patients, has been described previously,
      whereas the two others, P399L and R453Q, are novel mutations. In addition to the
      results demonstrating the involvement of MECP2 in MRX, this study shows that the
      frequency of mutations in MECP2 in the mentally retarded population screened for
      the fragile X syndrome is comparable to the frequency of the CGG expansions in
      FMR1. Therefore, implementation of systematic screening of MECP2 in MR patients
      should result in significant progress in the field of molecular diagnosis and
      genetic counseling of mental handicap.

PMID- 11309368
TI  - Connexin 31 (GJB3) is expressed in the peripheral and auditory nerves and causes
      neuropathy and hearing impairment.
AB  - Mutations in the connexin 31 (GJB3) gene have been found in subjects with
      dominant and recessive deafness and in patients with erythrokeratodermia
      variabilis. We report here a dominant mutation in the GJB3 gene (D66del) in a
      family affected with peripheral neuropathy and sensorineural hearing impairment.
      A wide range of disease severity for peripheral neuropathy, from asymptomatic
      cases to subjects with chronic skin ulcers in their feet and osteomyelitis
      leading to amputations, was detected in D66del patients. Mild, often
      asymmetrical, hearing impairment was found in all but one patient with mutation
      D66del of this family and the same mutation was present in an independent family
      ascertained because of hearing impairment. We have found mouse connexin 31 (Gjb3)
      gene expression in the cochlea and in the auditory and sciatic nerves, showing a
      pattern similar to that of Gjb1 (connexin 32), of which the human ortholog (GJB1)
      is involved in X-linked peripheral neuropathy. This expression pattern, together
      with auditory-evoked brainstem anomalous response in D66del patients, indicates
      that hearing impairment due to GJB3 mutations involves alterations in both the
      cochlea and the auditory nerve. Peripheral neuropathy is the third phenotypic
      alteration linked to GJB3 mutations, which enlarges the list of genes that cause
      this group of heterogeneous disorders.

PMID- 11309369
TI  - Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein.
AB  - Anhidrotic ectodermal dysplasia (EDA) is an X-linked disorder characterized by
      abnormal development of ectoderm and its appendices. The EDA gene encodes
      different isoforms of ectodysplasin, a transmembrane protein. The two longest
      isoforms, ectodysplasin-A1 and -A2, which differ by an insertion of two amino
      acids, are trimeric type II membrane proteins with an extracellular portion
      containing a short collagenous domain and a TNF ligand motif in the C-terminal
      region. We show that ectodysplasin is released from cells to the culture medium.
      Deletion constructs were used to localize the cleavage site and show that the
      putative recognition sequence of a furin-like enzyme is needed for the cleavage.
      Some EDA patients have missense mutations affecting this recognition sequence,
      suggesting that cleavage has biological significance in vivo. EDAR, a recently
      cloned member of the TNFR family and the product of the downless gene, is able to
      co-precipitate ectodysplasin, confirming that they form a ligand-receptor pair.
      In situ hybridization and immunostaining studies show that ectodysplasin and EDAR
      are expressed in adjacent or partially overlapping layers in the developing human
      skin. We conclude that as a soluble ligand, ectodysplasin is able to interact
      with EDAR and mediate signals needed for the development of ectodermal
      appendages.

PMID- 11309370
TI  - Analysis of a malsegregating mouse Y chromosome: evidence that the earliest
      cleavage divisions of the mammalian embryo are non-disjunction-prone.
AB  - Despite the clinical importance of human aneuploidy, we know little of the causes
      of mammalian non-disjunction. In part, this reflects the fact that, unlike lower
      organisms, segregation 'impaired' chromosomes are virtually non-existent in
      mammals. To address this issue, we have studied the mouse Y chromosome on the
      BALB/cWt ('Wt') inbred background, a system in which loss of the Y chromosome in
      gonadal tissue has been linked to hermaphroditism. Our results indicate that the
      Wt Y chromosome is stably transmitted during meiotic cell divisions, but non
      disjoins at an extremely high frequency in mitosis. Surprisingly, the non
      disjunction events are largely restricted to the earliest cleavage divisions,
      indicating that there is a temporal 'window' during which the Wt Y chromosome is
      susceptible to non-disjunction. The non-disjunction phenotype has both cis and
      trans components: the Wt Y chromosome malsegregates on a variety of genetic
      backgrounds, demonstrating an intrinsic defect; however, the incidence of non
      disjunction is significantly influenced by strain background, indicating the
      existence of modifying loci and thus providing evidence for a genetic effect on
      mammalian non-disjunction. These studies suggest that the earliest cell divisions
      in mammals are non-disjunction-prone, an interpretation which provides an
      explanation for the high rate of chromosome mosaicism observed in studies of in
      vitro fertilization (IVF)-derived human preimplantation embryos. Further, our
      observations raise the possibility that the IVF setting adversely affects
      chromosome segregation and suggest that genetic quality be an important
      consideration in any attempt to improve or modify in vitro procedures for use on
      human eggs and embryos.

PMID- 11309371
TI  - Molecular pathogenesis of a disease: structural consequences of
      aspartylglucosaminuria mutations.
AB  - A deficiency of functional aspartylglucosaminidase (AGA) causes a lysosomal
      storage disease, aspartylglucosaminuria (AGU). The recessively inherited disease
      is enriched in the Finnish population, where 98% of AGU alleles contain one
      founder mutation, AGU(Fin). Elsewhere in the world, we and others have described
      18 different sporadic AGU mutations. Many of these are predicted to interfere
      with the complex intracellular maturation and processing of the AGA polypeptide.
      Proper initial folding of AGA in the endoplasmic reticulum (ER) is dependent on
      intramolecular disulfide bridge formation and dimerization of two precursor
      polypeptides. The subsequent activation of AGA occurs autocatalytically in the ER
      and the protein is transported via the Golgi to the lysosomal compartment using
      the mannose-6-phosphate receptor pathway. Here we use the three-dimensional
      structure of AGA to predict structural consequences of AGU mutations, including
      six novel mutations, and make an effort to characterize every known disease
      mutation by dissecting the effect of mutations on intracellular stability,
      maturation, transport and the activity of AGA. Most mutations are substitutions
      replacing the original amino acid with a bulkier residue. Mutations of the dimer
      interface prevent dimerization in the ER, whereas active site mutations not only
      destroy the activity but also affect maturation of the precursor. Depending on
      their effects on the AGA polypeptide the mutations can be categorized as mild,
      moderate or severe. These data contribute to the expanding body of knowledge
      pertaining to molecular pathogenesis of AGU.

PMID- 11309372
TI  - Recovery from arterial growth delay reduces penetrance of cardiovascular defects
      in mice deleted for the DiGeorge syndrome region.
AB  - Chromosome 22q11.2 heterozygous deletions cause the most common deletion
      syndrome, including the DiGeorge syndrome phenotype. Using a mouse model of this
      deletion (named Df1) we show that the aortic arch patterning defects that occur
      in heterozygously deleted mice (Df1/+) are associated with a differentiation
      impairment of vascular smooth muscle in the 4th pharyngeal arch arteries (PAAs)
      during early embryogenesis. Using molecular markers for neural crest, endothelial
      cells and vascular smooth muscle, we show that cardiac neural crest migration
      into the 4th arch and initial formation of the 4th PAAs are apparently normal in
      Df1/+ embryos, but affected vessels are growth-impaired and do not acquire
      vascular smooth muscle. As in humans, not all deleted mice present with
      cardiovascular defects at birth. However, we found, unexpectedly, that all Df1/+
      embryos have abnormally small 4th PAAs during early embryogenesis. Many embryos
      later overcome this early defect, coincident with the appearance of vascular
      smooth muscle differentiation, and develop normally. Embryos born with aortic
      arch patterning defects probably represent a more severely affected group that
      fails to attain sufficient 4th PAA growth for normal remodelling of the PAA
      system. Our data indicate that Df1/+ embryos are able to overcome a localized
      arterial growth impairment and thereby reduce the penetrance of birth defects.

PMID- 11309373
TI  - Tissue-specific and ubiquitous promoters direct the expression of alternatively
      spliced transcripts from the calcitonin receptor gene.
AB  - The gene encoding the murine calcitonin receptor (mCTR) was isolated, and the
      exon/intron structure was determined. Analysis of transcripts revealed novel cDNA
      sequences, new alternative exon splicing in the 5'-untranslated region, and three
      putative promoters (P1, P2, and P3). The longest transcription unit is greater
      than 67 kilobase pairs, and the location of introns within the coding region of
      the mCTR gene (exons E3-E14) are identical to those of the porcine and human CTR
      genes. We have identified novel cDNA sequences that form three new exons as well
      as others that add 512 base pairs to the 5' side of the previously published
      cDNA, thereby extending exon E1 to 682 base pairs. Two of these novel exons are
      upstream of exon E2 and form a tripartite exon E2 (E2a, E2b, and E2c) in which
      E2a is utilized by promoter P2 with variable splicing of E2b. The third new exon
      (E3b') lies between E3a and E3b and is utilized by promoter P3. Analysis of mCTR
      mRNAs has revealed that the three alternative promoters give rise to at least
      seven mCTR isoforms in the 5' region of the gene and generate 5'-untranslated
      regions of very different lengths. Analysis by reverse transcription-polymerase
      chain reaction shows that promoters P1 and P2 are utilized in osteoclasts, brain,
      and kidney, whereas promoter P3 appears to be osteoclast-specific. Using
      transiently transfected reporter constructs, promoter P2 has activity in both a
      murine kidney cell line (MDCT209) and a chicken osteoclast-like cell line (HD
      11EM), whereas promoter P3 is active only in the osteoclast-like cell line. These
      transfection data confirm the osteoclast specificity of promoter P3 and provide
      the first evidence that the CTR gene is regulated in a tissue-specific manner by
      alternative promoter utilization.

PMID- 11309374
TI  - Functional assignment of the 20 S proteasome from Trypanosoma brucei using mass
      spectrometry and new bioinformatics approaches.
AB  - As experimental technologies for characterization of proteomes emerge,
      bioinformatic analysis of the data becomes essential. Separation and
      identification technologies currently based on two-dimensional gels/mass
      spectrometry provide the inherent analytical power required. This strategy
      involves protein spot digestion and accurate mass mapping together with
      computational interrogation of available data bases for protein functional
      identification. When either no exact match is found or when the possible matches
      only partially account for molecular weights actually observed, peptide
      sequencing by tandem mass spectrometry has emerged as the methodology of choice
      to provide the basic additional information required. To evaluate the
      capabilities of bioinformatics methods employed for identifying homologs of a
      protein of interest, we attempted to identify the major proteins from the 20 S
      proteasome of Trypanosoma brucei using sequence information determined using mass
      spectrometry. The results suggest that neither the traditional query engines,
      BLAST and FASTA, nor specialized software developed for analysis of sequence
      information obtained by mass spectrometry are able to identify even closely
      related sequences at statistically significant scores. To address this deficit,
      new bioinformatics approaches were developed for concomitant use of the multiple
      fragments of short sequence typically available from methods of tandem mass
      spectrometry. These approaches rely on the occurrence of congruence across
      searches of multiple fragments from a single protein. This method resulted in
      sharply better statistical significance values for correct hits in the data base
      output relative to that achieved for independent searches using single sequence
      fragments.

PMID- 11309375
TI  - The nuclear ubiquitin-proteasome system degrades MyoD.
AB  - Many short-lived nuclear proteins are targeted for degradation by the ubiquitin
      proteasome pathway. The role of the nucleus in regulating the turnover of these
      proteins is not well defined, although many components of the ubiquitin
      proteasome system are localized in the nucleus. We have used nucleoplasm from
      highly purified HeLa nuclei to examine the degradation of a physiological
      substrate of the ubiquitin-proteasome system (MyoD). In vitro studies using
      inhibitors of the system demonstrate MyoD is degraded via the ubiquitin
      proteasome pathway in HeLa nucleoplasm. Purified nucleoplasm in vitro also
      supports the generation of high molecular mass MyoD-ubiquitin adducts. In
      addition, in vivo studies, using leptomycin B to inhibit nuclear export,
      demonstrate that MyoD is degraded in HeLa cells by the nuclear ubiquitin
      proteasome system.

PMID- 11309376
TI  - Real-time analysis of G protein-coupled receptor reconstitution in a solubilized
      system.
AB  - Receptor based signaling mechanisms are the primary source of cellular
      regulation. The superfamily of G protein-coupled receptors is the largest and
      most ubiquitous of the receptor mediated processes. We describe here the analysis
      in real-time of the assembly and disassembly of soluble G protein-coupled
      receptor-G protein complexes. A fluorometric method was utilized to determine the
      dissociation of a fluorescent ligand from the receptor solubilized in detergent.
      The ligand dissociation rate differs between a receptor coupled to a G protein
      and the receptor alone. By observing the sensitivity of the dissociation of a
      fluorescent ligand to the presence of guanine nucleotide, we have shown a time-
      and concentration-dependent reconstitution of the N-formyl peptide receptor with
      endogenous G proteins. Furthermore, after the clearing of endogenous G proteins,
      purified Galpha subunits premixed with bovine brain Gbetagamma subunits were also
      able to reconstitute with the solubilized receptors. The solubilized N-formyl
      peptide receptor and Galpha(i3) protein interacted with an affinity of
      approximately 10(-6) m with other alpha subunits exhibiting lower affinities
      (Galpha(i3) > Galpha(i2) > Galpha(i1) Galpha(o)). The N-formyl peptide receptor-G
      protein interactions were inhibited by peptides corresponding to the Galpha(i) C
      terminal regions, by Galpha(i) mAbs, and by a truncated form of arrestin-3. This
      system should prove useful for the analysis of the specificity of receptor-G
      protein interactions, as well as for the elucidation and characterization of
      receptor molecular assemblies and signal transduction complexes.

PMID- 11309377
TI  - The nucleolar phosphoprotein B23 interacts with hepatitis delta antigens and
      modulates the hepatitis delta virus RNA replication.
AB  - Hepatitis delta virus (HDV) encodes two isoforms of delta antigens (HDAgs). The
      small form of HDAg is required for HDV RNA replication, while the large form of
      HDAg inhibits the viral replication and is required for virion assembly. In this
      study, we found that the expression of B23, a nucleolar phosphoprotein involved
      in disparate functions including nuclear transport, cellular proliferation, and
      ribosome biogenesis, is up-regulated by these two HDAgs. Using in vivo and in
      vitro experimental approaches, we have demonstrated that both isoforms of HDAg
      can interact with B23 and their interaction domains were identified as the NH(2)
      terminal fragment of each molecule encompassing the nuclear localization signal
      but not the coiled-coil region of HDAg. Sucrose gradient centrifugation analysis
      indicated that the majority of small HDAg, but a lesser amount of the large HDAg,
      co-sedimented with B23 and nucleolin in the large nuclear complex. Transient
      transfection experiments also indicated that introducing exogenous full-length
      B23, but not a mutated B23 defective in HDAg binding, enhanced HDV RNA
      replication. All together, our results reveal that HDAg has two distinct effects
      on nucleolar B23, up-regulation of its gene expression and the complex formation,
      which in turn regulates HDV RNA replication. Therefore, this work demonstrates
      the important role of nucleolar protein in regulating the HDV RNA replication
      through the complex formation with the key positive regulator being small HDAg.

PMID- 11309378
TI  - The DNA binding activity of the RIPE3b1 transcription factor of insulin appears
      to be influenced by tyrosine phosphorylation.
AB  - The RIPE3b1 DNA binding factor plays a critical role in pancreatic islet beta
      cell-specific and glucose-regulated transcription of the insulin gene. Recently
      it was shown that RIPE3b1 binding activity in beta cell nuclear extracts is
      reduced by treatment with either calf intestinal alkaline phosphatase (CIAP) or a
      brain-enriched phosphatase preparation (BPP) (Zhao, L., Cissell, M. A.,
      Henderson, E., Colbran, R., and Stein, R. (2000) J. Biol. Chem. 275, 10532
      10537). Evidence is presented here suggesting that a tyrosine phosphatase(s)
      influences the ability of RIPE3b1 to bind to the insulin C1 element in beta
      cells. We found that RIPE3b1 binding was inhibited upon incubating beta cell
      nuclear extracts at 30 degrees C. In contrast, PDX-1 and MLTF-1 transcription
      factor binding activity was unaffected under these conditions. The loss in
      RIPE3b1 binding activity was prevented by inhibitors of tyrosine phosphatases
      (sodium orthovanadate and sodium molybdate) but not by inhibitors of
      serine/threonine phosphatases (sodium fluoride, okadaic acid, and microcystin
      LR). CIAP- and BPP-catalyzed inhibition of RIPE3b1 binding was also blocked by
      these tyrosine phosphatase inhibitors. Collectively, the data suggested that
      removal of a tyrosine(s) within RIPE3b1 prevented activator binding to insulin C1
      control element sequences. The presence of a key phosphorylated tyrosine(s)
      within this transcription factor was further supported by the ability of the 4G10
      anti-phosphotyrosine monoclonal antibody to immunoprecipitate RIPE3b1 DNA binding
      activity. We discuss how tyrosine phosphorylation, a very rare and highly
      significant regulatory modification, may control RIPE3b1 activator function.

PMID- 11309379
TI  - Accurate in vitro end joining of a DNA double strand break with partially
      cohesive 3'-overhangs and 3'-phosphoglycolate termini: effect of Ku on repair
      fidelity.
AB  - To examine determinants of fidelity in DNA end joining, a substrate containing a
      model of a staggered free radical-mediated double-strand break, with cohesive
      phosphoglycolate-terminated 3'-overhangs and a one-base gap in each strand, was
      constructed. In extracts of Xenopus eggs, human lymphoblastoid cells, hamster CHO
      K1 cells, and a Chinese hamster ovary (CHO) derivative lacking the catalytic
      subunit of DNA-dependent protein kinase (DNA-PKcs), the predominant end joining
      product was that corresponding to accurate restoration of the original sequence.
      In extracts of the Ku-deficient CHO derivative xrs6, a shorter product,
      consistent with 3' --> 5' resection before ligation, was formed. Similar results
      were seen for a substrate with 5'-overhangs and recessed 3'-phosphoglycolate
      ends. Supplementation of the xrs6 extracts with purified Ku restored accurate end
      joining. In Xenopus and human extracts, but not in hamster extracts, gap filling
      and ligation were blocked by wortmannin, consistent with a requirement for DNA
      PKcs activity. The results suggest a Ku-dependent pathway, regulated by DNA-PKcs,
      that can accurately restore the original DNA sequence at sites of free radical
      mediated double-strand breaks, by protecting DNA termini from degradation and
      maintaining the alignment of short partial complementarities during gap filling
      and ligation.

PMID- 11309380
TI  - BetaPix-enhanced p38 activation by Cdc42/Rac/PAK/MKK3/6-mediated pathway.
      Implication in the regulation of membrane ruffling.
AB  - betaPix (PAK-interacting exchange factor) is a recently identified guanine
      nucleotide exchange factor for Rho family small G protein Cdc42/Rac. The protein
      interacts with p21-activated protein kinase (PAK) through its SH3 domain. We
      examined the effect of betaPix on MAP kinase signaling and cytoskeletal
      rearrangement in NIH3T3 fibroblast cells. Overexpression of betaPix enhanced the
      activation of p38 in the absence of other stimuli and also induced translocation
      of p38 to the nucleus. This betaPix-induced p38 activation was blocked by
      coexpression of dominant-negative Cdc42/Rac or kinase-inactive PAK, indicating
      that the effect of betaPix on p38 is exerted through the Cdc42/Rac-PAK pathway
      and requires PAK kinase activity. The essential role of betaPix in growth factor
      stimulated p38 activation was evidenced by the blocking of platelet-derived
      growth factor-induced p38 activation in the cells expressing betaPix SH3m (W43K)
      and betaPix DHm (L238R,L239R). In addition, SB203580, a p38 inhibitor, and kinase
      inactive p38 (T180A,Y182F) blocked membrane ruffling induced by betaPix,
      suggesting that p38 might be involved in mediating betaPix-induced membrane
      ruffling. The results in this study suggest that betaPix might have a role in
      nuclear signaling, as well as in actin cytoskeleton regulation, and that some
      part of these cellular functions is possibly mediated by p38 MAP kinase.

PMID- 11309381
TI  - The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250)
      binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu
      413 domain and provides a mobile scaffold during desensitization.
AB  - The cyclic AMP-dependent kinase-anchoring proteins (AKAPs) function as scaffolds
      for a wide-range of protein-protein interactions. The 250-kDa AKAP known as
      gravin plays a central role in organizing G-protein-coupled receptors to the
      protein kinases and phosphatases that regulate receptor function in
      desensitization, resensitization, and sequestration. Although gravin is critical
      for G-protein-linked receptor biology, the molecular features of the receptor
      necessary for interaction with this scaffold are not known. Herein, we map the
      regions of the beta(2)-adrenergic receptor that are required for binding to
      gravin. Intracellular loops 1, 2, and 3 appear not to participate in the binding
      of the receptor to the scaffold. In contrast, the C-terminal cytoplasmic region
      of the receptor (Arg-329 to Leu-413) competes readily for the binding of the
      beta(2)-adrenergic receptor by gravin, both using in vitro and in vivo assays. C
      terminally truncated peptides with sequences ranging from Arg-329 to Leu-342 (13
      aminoacyl residues), to Asn-352 (23 residues), to Tyr-366 (37 residues), to Asp
      380 (51 residues), or to His-390 (61 residues), as well as N-terminally truncated
      peptides from Gln-391 to Leu-413 (23 residues) or Leu-381 to Leu-413 (33
      residues) displayed no ability to block binding of receptor to gravin. The
      combination of Arg-329 to His-390 peptide and Gln-391 to Leu-413 peptide,
      however, reconstitutes a fragmented but full-length C-terminal region and also
      potently blocks the ability of gravin to bind the beta(2)-adrenergic receptor.
      The gravin-receptor interaction was examined in response to agonist by confocal
      microscopy. Remarkably, the association of the receptor with gravin was not
      disrupted during agonist-induced sequestration. The receptor-scaffold complex was
      maintained during agonist-induced sequestration. These data, in agreement with
      the biochemical data, reveal that gravin binds the receptor through the beta(2)
      adrenergic receptor C-terminal cytoplasmic domain and that this interaction is
      maintained as the receptor is internalized. This is the first report of an AKAP
      scaffold protein translocating with its receptor, in this case a G-protein
      coupled receptor.

PMID- 11309382
TI  - Inhibition of c-Abl tyrosine kinase activity by filamentous actin.
AB  - The catalytic activity of c-Abl tyrosine kinase is reduced in fibroblasts that
      are detached from the extracellular matrix. We report here that a deletion of the
      extreme C terminus of c-Abl (DeltaF-actin c-Abl) can partially restore kinase
      activity to c-Abl from detached cells. Because the extreme C terminus of c-Abl
      contains a consensus F-actin binding motif, we investigated the effect of F-actin
      on c-Abl tyrosine kinase activity. We found that F-actin can inhibit the kinase
      activity of purified c-Abl protein. Mutations of the extreme C-terminal region of
      c-Abl disrupted both the binding of c-Abl to F-actin and the inhibition of c-Abl
      by F-actin. Mutations of the SH3, SH2, and DNA binding domains did not abolish
      the inhibition of c-Abl kinase by F-actin. Catalytic domain substitutions that
      affect the regulation of c-Abl by the retinoblastoma protein or the ataxia
      telangiectasia-mutated kinase also did not abolish the inhibition of c-Abl by F
      actin. Interestingly, among these c-Abl mutants, only the DeltaF-actin c-Abl
      retained kinase activity in detached cells. Taken together, the data suggest that
      F-actin is an inhibitor of the c-Abl tyrosine kinase and that this inhibition
      contributes in part to the reduced Abl kinase activity in detached cells.

PMID- 11309383
TI  - G-protein-independent activation of Tyk2 by the platelet-activating factor
      receptor.
AB  - Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid with
      multiple physiological and pathological effects. PAF exerts its activity through
      a specific heptohelical G-protein coupled receptor, expressed on a variety of
      cell types, including leukocytes. In this study, we showed that PAF induced a
      rapid tyrosine phosphorylation of the Tyk2 kinase in the monocytic cell lines
      U937 and MonoMac-1. PAF-initiated Tyk2 phosphorylation was also observed in COS-7
      cells transiently transfected with the human PAF receptor (PAFR) and Tyk2 cDNAs.
      In addition, we found that Tyk2 co-immunoprecipitated and co-localized with PAFR,
      independently of ligand binding. Deletion mutants of Tyk2 indicated that the N
      terminus of the kinase was important for the binding to PAFR. Activation of Tyk2
      was followed by a time-dependent 2-4-fold increase in the level of tyrosine
      phosphorylation of signal transducers and activators of transcription 1 (STAT1),
      STAT2, and STAT3 and a sustained 2.5-fold increase in STAT5 tyrosine
      phosphorylation. In MonoMac-1 cells, STAT1 and STAT3 translocated to the nucleus
      following PAF stimulation, and their translocation in transiently transfected COS
      7 cells was shown to be dependent on the presence of Tyk2. In addition, when COS
      7 cells were transfected with PAFR and constructs containing PAFR promoter 1,
      coupled to the luciferase reporter gene, PAF induced a 3.6-fold increase in
      promoter activation in the presence of Tyk2. Finally, PAFR mutants that could not
      couple to G-proteins were found to effectively mediate Tyk2 activation and
      signaling. Taken together, these findings suggest an important role for the Janus
      kinase/STAT pathway in PAFR signaling, independent of G-proteins, and in the
      regulation of PAF receptor expression by its ligand.

PMID- 11309384
TI  - Identification and mapping of protein-protein interactions between gp32 and gp59
      by cross-linking.
AB  - The bacteriophage T4 59 protein (gp59) plays a vital role in recombination and
      replication by promoting the assembly of the gene 41 helicase (gp41) onto DNA,
      thus enabling replication as well as strand exchange in recombination. Loading of
      the helicase onto gp32 (the T4 single strand binding protein)-coated single
      stranded DNA requires gp59 to remove gp32 and replace it with gp41. Cross-linking
      studies between gp32 and gp59 reveal an interaction between Cys-166 of gp32 and
      Cys-42 of gp59. Since Cys-166 lies in the DNA binding core domain of gp32, this
      interaction may affect the association of gp32 with DNA. In the presence of gp32
      or DNA, gp59 is capable of forming a multimer consisting of at least five gp59
      subunits. Kinetics studies suggest that gp59 and gp41 exist in a one-to-one
      ratio, predicting that gp59 is capable of forming a hexamer (Raney, K. D.,
      Carver, T. E., and Benkovic, S. J. (1996) J. Biol. Chem. 271, 14074-14081). The C
      terminal A-domain of gp32 is needed for gp59 oligomer formation. Cross-linking
      has established that gp59 can interact with gp32-A (a truncated form of gp32
      lacking the A-domain) but cannot form higher species. The results support a model
      in which gp59 binds to gp32 on a replication fork, destabilizing the gp32-single
      stranded DNA interaction concomitant with the oligomerization of gp59 that
      results in a switching of gp41 for gp32 at the replication fork.

PMID- 11309385
TI  - A new role for E12/E47 in the repression of E-cadherin expression and epithelial
      mesenchymal transitions.
AB  - Down-regulation of E-cadherin expression is a determinant of tumor cell
      invasiveness, an event frequently associated with epithelial-mesenchymal
      transitions. Here we show that the mouse E12/E47 basic helix-loop-helix
      transcription factor (the E2A gene product) acts as a repressor of E-cadherin
      expression and triggers epithelial-mesenchymal transitions. The mouse E47 factor
      was isolated in a one-hybrid system designed to isolate repressors of the mouse E
      cadherin promoter. Epithelial cells ectopically expressing E47 adopt a
      fibroblastic phenotype and acquire tumorigenic and migratory/invasive properties,
      concomitant with the suppression of E-cadherin expression. Suppression of E
      cadherin expression under stable or inducible expression of E47 in epithelial
      cells occurs at the transcriptional level and is dependent on the E-boxes of the
      E-cadherin promoter. Interestingly, analysis of endogenous E2A expression in
      murine and human cell lines illustrated its presence in E-cadherin-deficient,
      invasive carcinoma cells but its absence from epithelial cell lines. This
      expression pattern is consistent with that observed in early mouse embryos, where
      E2A mRNA is absent from epithelia but strongly expressed in the mesoderm. These
      results implicate E12/E47 as a repressor of E-cadherin expression during both
      development and tumor progression and indicate its involvement in the acquisition
      and/or maintenance of the mesenchymal phenotype.

PMID- 11309386
TI  - In vivo role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the regulation of
      intracellular redox state and accumulation of abdominal adipose tissue.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoprotein that utilizes NAD(P)H
      as an electron donor, catalyzing the two-electron reduction and detoxification of
      quinones and their derivatives. NQO1-/- mice deficient in NQO1 activity and
      protein were generated in our laboratory (Rajendirane, V., Joseph, P., Lee, Y.
      H., Kimura, S., Klein-Szanto, A. J. P., Gonzalez, F. J., and Jaiswal, A. K.
      (1998) J. Biol. Chem. 273, 7382-7389). Mice lacking a functional NQO1 gene (NQO1
      /-) were born normal and reproduced adeptly as the wild-type NQO1+/+ mice. In the
      present report, we show that NQO1-/- mice exhibit significantly lower levels of
      abdominal adipose tissue as compared with the wild-type mice. The NQO1-/- mice
      showed lower blood levels of glucose, no change in insulin, and higher levels of
      triglycerides, beta-hydroxy butyrate, pyruvate, lactate, and glucagon as compared
      with wild-type mice. Insulin tolerance test demonstrated that the NQO1-/- mice
      are insulin resistant. The NQO1-/- mice livers also showed significantly higher
      levels of triglycerides, lactate, pyruvate, and glucose. The liver glycogen
      reserve was found decreased in NQO1-/- mice as compared with wild-type mice. The
      livers and kidneys from NQO1-/- mice also showed significantly lower levels of
      pyridine nucleotides but an increase in the reduced/oxidized NAD(P)H:NAD(P)
      ratio. These results suggested that loss of NQO1 activity alters the
      intracellular redox status by increasing the concentration of NAD(P)H. This leads
      to a reduction in pyridine nucleotide synthesis and reduced glucose and fatty
      acid metabolism. The alterations in metabolism due to redox changes result in a
      significant reduction in the amount of abdominal adipose tissue.

PMID- 11309387
TI  - Induction of apoptosis and Fas receptor/Fas ligand expression by
      ischemia/reperfusion in cardiac myocytes requires serine 727 of the STAT-1
      transcription factor but not tyrosine 701.
AB  - Previously we reported that ischemia results in apoptosis and is accompanied by
      phosphorylation on Tyr-701 and increased expression and transcriptional activity
      of the signal transducer and activator of transcription-1 (STAT-1). In the
      present study, we show that exposure of cardiomyocytes to ischemia induced the
      phosphorylation of STAT-1 at another site, Ser-727. Moreover, STAT-1 is critical
      for the induction of Fas receptor and Fas ligand expression by
      ischemia/reperfusion (I/R). Transcriptional activation of Fas and FasL was
      dependent on Ser-727 of STAT-1 but was independent of Tyr-701. Similarly, Ser-727
      but not Tyr-701 was required for enhancement of cardiomyocyte cell death by STAT
      1 during I/R. In addition, inhibition of the p38 pathway prevented the induction
      and transcriptional activation of Fas and FasL in cardiac cells exposed to I/R,
      whereas inhibition of p42/p44 MAPK had no effect. Finally, I/R also induced
      phosphorylation of STAT-1 on Ser-727 and expression of Fas/FasL in ventricular
      myocytes in the intact heart ex vivo. These results indicate that Fas/FasL genes
      and apoptosis are activated by STAT-1 in cardiac myocytes exposed to I/R and
      these effects are dependent on the Ser-727 but not the Tyr-701 phosphorylation
      sites of STAT-1.

PMID- 11309388
TI  - Pdx1 level defines pancreatic gene expression pattern and cell lineage
      differentiation.
AB  - The absence of Pdx1 and the expression of brain-4 distinguish alpha-cells from
      other pancreatic endocrine cell lineages. To define the transcription factor
      responsible for pancreatic cell differentiation, we employed the reverse
      tetracycline-dependent transactivator system in INS-I cell-derived subclones
      INSralphabeta and INSrbeta to achieve tightly controlled and conditional
      expression of wild type Pdx1 or its dominant-negative mutant, as well as brain-4.
      INSralphabeta cells express not only insulin but also glucagon and brain-4, while
      INSrbeta cells express only insulin. Overexpression of Pdx1 eliminated glucagon
      mRNA and protein in INSralphabeta cells and promoted the expression of beta-cell
      specific genes in INSrbeta cells. Induction of dominant-negative Pdx1 in
      INSralphabeta cells resulted in differentiation of insulin-producing beta-cells
      into glucagon-containing alpha-cells without altering brain4 expression. Loss of
      Pdx1 function alone in INSrbeta cells, which do not express endogenous brain-4
      and glucagon, was also sufficient to abolish the expression of genes restricted
      to beta-cells and to cause alpha-cell differentiation. In contrast, induction of
      brain-4 in INSrbeta cells initiated detectable expression of glucagon but did not
      affect beta-cell-specific gene expression. In conclusion, Pdx1 confers the
      expression of pancreatic beta-cell-specific genes, such as genes encoding
      insulin, islet amyloid polypeptide, Glut2, and Nkx6.1. Pdx1 defines pancreatic
      cell lineage differentiation. Loss of Pdx1 function rather than expression of
      brain4 is a prerequisite for alpha-cell differentiation.

PMID- 11309389
TI  - Growth hormone (GH)-induced dimerization inhibits phorbol ester-stimulated GH
      receptor proteolysis.
AB  - Growth hormone (GH) initiates its cellular action by properly dimerizing GH
      receptor (GHR). A substantial fraction of circulating GH is complexed with a high
      affinity GH-binding protein (GHBP) that in many species can be generated by GHR
      proteolysis and shedding of the receptor's ligand-binding extracellular domain.
      We previously showed that this proteolysis 1) can be acutely promoted by the
      phorbol ester phorbol 12-myristate 13-acetate (PMA), 2) requires a
      metalloprotease activity, 3) generates both shed GHBP and a membrane-associated
      GHR transmembrane/cytoplasmic domain remnant, and 4) results in down-regulation
      of GHR abundance and GH signaling. Using cell culture model systems, we now
      explore the effects of GH treatment on inducible GHR proteolysis and GHBP
      shedding. In human IM-9 lymphocytes, which endogenously express GHRs, and in
      Chinese hamster ovary cells heterologously expressing wild-type or cytoplasmic
      domain internal deletion mutant rabbit GHRs, brief exposure to GH inhibited PMA
      induced GHR proteolysis (receptor loss and remnant accumulation) by 60-93%. PMA
      induced shedding of GHBP from Chinese hamster ovary transfectants was also
      inhibited by 70% in the presence of GH. The capacity of GH to inhibit inducible
      GHR cleavage did not rely on JAK2-dependent GH signaling, as evidenced by its
      continued protection in JAK2-deficient gamma2A rabbit GHR cells. The GH
      concentration dependence for inhibition of PMA-induced GHR proteolysis paralleled
      that for its promotion of receptor dimerization (as monitored by formation of GHR
      disulfide linkage). Unlike GH, the GH antagonist, G120K, which binds to but fails
      to properly dimerize GHRs, alone did not protect against PMA-induced GHR
      proteolysis; G120K did, however, antagonize the protective effect of GH. Our data
      suggest that GH inhibits PMA-induced GHR proteolysis and GHBP shedding by
      inducing GHR dimerization and that this effect does not appear to be related to
      GH site 1 binding, GHR internalization, or GHR signaling. The implications of
      these findings with regard to GH signaling and GHR down-regulation are discussed.

PMID- 11309390
TI  - Endoplasmic reticulum D-myo-inositol 1,4,5-trisphosphate-sensitive stores
      regulate nuclear factor-kappaB binding activity in a calcium-independent manner.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) plays critical roles
      in neuronal survival and plasticity and in activation of immune responses. The
      activation of NF-kappaB has been closely associated with changes in intracellular
      calcium levels, but the relationship between the two remains unclear. Here we
      report that inhibition of endoplasmic reticulum (ER) d-myo-inositol 1,4,5
      trisphosphate (IP(3))-gated calcium release caused decreased basal NF-kappaB DNA
      binding activity in cultured rat cortical neurons. Activation of NF-kappaB in
      response to tumor necrosis factor-alpha and glutamate was completely abolished
      when IP(3) receptors were blocked, and NF-kappaB activation in response to
      depletion of ER calcium by thapsigargin treatment was also decreased by IP(3)
      receptor blockade. We further investigated the relationship between IP(3)
      receptor activation and NF-kappaB activity using a cell-free system. Microsomes
      enriched in the ER were isolated from adult rat cerebral cortex, resuspended, and
      treated with agents that induce or inhibit ER calcium release. They were then
      recentrifuged, and the supernatant was added to cytoplasmic extract isolated from
      the same source tissue. We found that microsomes released an NF-kappaB
      stimulating signal in response to activation of IP(3) receptors or inhibition of
      the ER Ca(2+)-ATPase, but not in response to ryanodine. Studies of intact cells
      and cell-free preparations indicated that the signal released from the ER was not
      calcium and was heat- and trypsin-sensitive. Our data suggest that activation of
      IP(3) receptors is required for a major component of both constitutive and
      inducible NF-kappaB binding activity in neurons and that decreasing ER
      intraluminal calcium levels triggers release of a diffusible NF-kappaB-activating
      signal from the ER.

PMID- 11309391
TI  - Hepatic glycogen synthesis is highly sensitive to phosphorylase activity:
      evidence from metabolic control analysis.
AB  - We used metabolic control analysis to determine the flux control coefficient of
      phosphorylase on glycogen synthesis in hepatocytes by titration with a specific
      phosphorylase inhibitor (CP-91149) or by expression of muscle phosphorylase using
      recombinant adenovirus. The muscle isoform was used because it is catalytically
      active in the b-state. CP-91149 inactivated phosphorylase with sequential
      activation of glycogen synthase. It increased glycogen synthesis by 7-fold at 5
      mm glucose and by 2-fold at 20 mm glucose with a decrease in the concentration of
      glucose causing half-maximal rate (S(0.5)) from 26 to 19 mm. Muscle phosphorylase
      was expressed in hepatocytes mainly in the b-state. Low levels of phosphorylase
      expression inhibited glycogen synthesis by 50%, with little further inhibition at
      higher enzyme expression, and caused inactivation of glycogen synthase that was
      reversed by CP-91149. At endogenous activity, phosphorylase has a very high
      (greater than unity) negative control coefficient on glycogen synthesis,
      regardless of whether it is determined by enzyme inactivation or overexpression.
      This high control is attenuated by glucokinase overexpression, indicating
      dependence on other enzymes with high control. The high control coefficient of
      phosphorylase on glycogen synthesis affirms that phosphorylase is a strong
      candidate target for controlling hyperglycemia in type 2 diabetes in both the
      absorptive and postabsorptive states.

PMID- 11309392
TI  - Nuclear diacylglycerol kinase-theta is activated in response to alpha-thrombin.
AB  - Currently, there is substantial evidence that nuclear lipid metabolism plays a
      critical role in a number of signal transduction cascades. Previous work from our
      laboratory showed that stimulation of quiescent fibroblasts with alpha-thrombin
      leads to the production of two lipid second messengers in the nucleus: an
      increase in nuclear diacylglycerol mass and an activation of phospholipase D,
      which catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic
      acid. Diacylglycerol kinase (DGK) catalyzes the conversion of diacylglycerol to
      phosphatidic acid, making it an attractive candidate for a signal transduction
      component. There is substantial evidence that this activity is indeed regulated
      in a number of signaling cascades (reviewed by van Blitterswijk, W. J., and
      Houssa, B. (1999) Chem. Phys. Lipids 98, 95-108). In this report, we show that
      the addition of alpha-thrombin to quiescent IIC9 fibroblasts results in an
      increase in nuclear DGK activity. The examination of nuclei isolated from
      quiescent IIC9 cells indicates that DGK-theta and DGK-delta are both present. We
      took advantage of the previous observations that phosphatidylserine inhibits DGK
      delta (reviewed by Sakane, F., Imai, S., Kai, M., Wada, I., and Kanoh, H. (1996)
      J. Biol. Chem. 271, 8394-8401), and constitutively active RhoA inhibits DGK-theta
      (reviewed by Houssa, B., de Widt, J., Kranenburg, O., Moolenaar, W. H., and van
      Blitterswijk, W. J. (1999) J. Biol. Chem. 274, 6820-6822) to identify the
      activity induced by alpha-thrombin. Constitutively active RhoA inhibited the
      nuclear stimulated activity, whereas phosphatidylserine did not have an
      inhibitory effect. In addition, a monoclonal anti-DGK-theta antibody inhibited
      the alpha-thrombin-stimulated nuclear activity in vitro. These results
      demonstrate that DGK-theta is the isoform responsive to alpha-thrombin
      stimulation. Western blot and immunofluorescence microscopy analyses showed that
      alpha-thrombin induced the translocation of DGK-theta to the nucleus, implicating
      that this translocation is at least partly responsible for the increased nuclear
      activity. Taken together, these data are the first to demonstrate an agonist
      induced activity of nuclear DGK-theta activity and a nuclear localization of DGK
      delta.

PMID- 11309393
TI  - Molecular determinants of the interaction between the inositol 1,4,5
      trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP kinase
      Ibeta.
AB  - Cyclic GMP-dependent protein kinase I (cGKI) affects the inositol 1,4,5
      trisphosphate (InsP(3))-dependent release of intracellular calcium by
      phosphorylation of IRAG (inositol 1,4,5-trisphophate receptor-associated cGMP
      kinase substrate). IRAG is present in a macromolecular complex with the InsP(3)
      receptor type I (InsP(3)RI) and cGKIbeta. The specificity of the interaction
      between these three proteins was investigated by using the yeast two-hybrid
      system and by co-precipitation of expressed proteins. The amino-terminal region
      containing the leucine zipper (amino acids 1-53) of cGKIbeta but not that of
      cGKIalpha or cGKII interacted with the sequence between amino acids 152 and 184
      of IRAG in vitro and in vivo most likely through electrostatic interaction.
      cGKIbeta did not interact with the InsP(3)RI, but co-precipitated the InsP(3)RI
      in the presence of IRAG indicating that IRAG bound to the InsP(3)RI and to
      cGKIbeta. cGKIbeta phosphorylated up to four serines in IRAG. Mutation of these
      four serines to alanine showed that cGKIbeta-dependent phosphorylation of
      Ser(696) is necessary to decrease calcium release from InsP(3)-sensitive stores.
      These results show that cGMP induced reduction of cytosolic calcium
      concentrations requires cGKIbeta and phosphorylation of Ser(696) of IRAG.

PMID- 11309394
TI  - A novel snare N-terminal domain revealed by the crystal structure of Sec22b.
AB  - Intra-cellular membrane fusion is facilitated by the association of SNAREs from
      opposite membranes into stable alpha-helical bundles. Many SNAREs, in addition to
      their alpha-helical regions, contain N-terminal domains that likely have
      essential regulatory functions. To better understand this regulation, we have
      determined the 2.4-A crystal structure of the 130-amino acid N-terminal domain of
      mouse Sec22b (mSec22b), a SNARE involved in endoplasmic reticulum/Golgi membrane
      trafficking. The domain consists of a mixed alpha-helical/beta-sheet fold that
      resembles a circular permutation of the actin/poly-proline binding protein,
      profilin, and the GAF/PAS family of regulatory modules. The structure is distinct
      from the previously characterized N-terminal domain of syntaxin 1A, and, unlike
      syntaxin 1A, the N-terminal domain of mSec22b has no effect on the rate of SNARE
      assembly in vitro. An analysis of surface conserved residues reveals a potential
      protein interaction site. Key residues in this site are distinct in two mammalian
      Sec22 variants that lack SNARE domains. Finally, sequence analysis indicates that
      a similar domain is likely present in the endosomal/lysosomal SNARE VAMP7.

PMID- 11309395
TI  - Specific binding of single-stranded telomeric DNA by Cdc13p of Saccharomyces
      cerevisiae.
AB  - Cdc13p is a single strand telomere-binding protein of Saccharomyces cerevisiae;
      its telomere-binding region is within amino acids 451-693, Cdc13(451-693)p. In
      this study, we used purified Cdc13p and Cdc13(451-693)p to characterize their
      telomere binding activity. We found that the binding specificity of single
      stranded TG(1-3) DNA by these two proteins is similar. However, the affinity of
      Cdc13(451-693)p to DNA was slightly lower than that of Cdc13p. The binding of
      telomeric DNA by these two proteins was disrupted at NaCl concentrations higher
      than 0.3 m, indicating that electrostatic interaction contributed significantly
      to the binding process. Because both proteins bound to strand TG(1-3) DNA
      positioned at the 3' end, the 5' end, or in the middle of the oligonucleotide
      substrates, our results indicated that the location of TG(1-3) in single-stranded
      DNA does not appear to be important for Cdc13p binding. Moreover, using DNase I
      footprint analysis, the structure of the telomeric DNA complexes of Cdc13p and
      Cdc13(451-693)p was analyzed. The DNase I footprints of these two proteins to
      three different telomeric DNA substrates were virtually identical, indicating
      that the telomere contact region of Cdc13p is within Cdc13(451-693)p. Together,
      the binding properties of Cdc13p and its binding domain support the theory that
      the specific binding of Cdc13p to telomeres is an important feature of telomeres
      that regulate telomerase access and/or differentiate natural telomeres from
      broken ends.

PMID- 11309396
TI  - Isolation of hyperactive mutants of the MAPK p38/Hog1 that are independent of
      MAPK kinase activation.
AB  - Mitogen-activated protein kinases (MAPKs) play pivotal roles in growth,
      development, differentiation, and apoptosis. The exact role of a given MAPK in
      these processes is not fully understood. This question could be addressed using
      active forms of these enzymes that are independent of external stimulation and
      upstream regulation. Yet, such molecules are not available. MAPK activation
      requires dual phosphorylation, on neighboring Tyr and Thr residues, catalyzed by
      MAPK kinases (MAPKKs). It is not known how to force MAPK activation independent
      of MAPKK phosphorylation. Here we describe a series of nine hyperactive
      (catalytically and biologically), MAPKK-independent variants of the MAPK Hog1.
      Each of the active molecules contains just a single point mutation. Six mutations
      are in the conserved L16 domain of the protein. The active Hog1 mutants were
      obtained through a novel genetic screen that could be applied for isolation of
      active MAPKs of other families. Equivalent mutations, introduced to the human
      p38alpha, rendered the enzyme active even when produced in Escherichia coli,
      showing that the mutations increased the intrinsic catalytic activity of p38. It
      implies that the activating mutations could be directly used for production of
      active forms of MAPKs from yeasts to humans and could open the way to revealing
      their biological functions.

PMID- 11309397
TI  - Protein kinase C-alpha signals rho-guanine nucleotide dissociation inhibitor
      phosphorylation and rho activation and regulates the endothelial cell barrier
      function.
AB  - The Rho-GDP guanine nucleotide dissociation inhibitor (GDI) complexes with the
      GDP-bound form of Rho and inhibits its activation. We investigated the role of
      protein kinase C (PKC) isozymes in the mechanism of Rho activation and in
      signaling the loss of endothelial barrier function. Thrombin and phorbol 12
      myristate 13-acetate induced rapid phosphorylation of GDI and the activation of
      Rho-A in human umbilical venular endothelial cells. Inhibition of PKC by
      chelerythrine chloride abrogated the thrombin-induced GDI phosphorylation and Rho
      activation. Depletion of PKC prevented the thrombin-induced GDI phosphorylation
      and Rho activation, thereby indicating that these events occurred downstream of
      phorbol ester-sensitive PKC isozyme activation. The depletion of PKC or
      inhibition of Rho by C3 toxin also prevented the thrombin-induced decrease in
      transendothelial electrical resistance (a measure of increased transendothelial
      permeability), thus indicating that PKC-induced barrier dysfunction was mediated
      through Rho-dependent pathway. Using inhibitors and dominant-negative mutants, we
      found that Rho activation was regulated by PKC-alpha. Moreover, the stimulation
      of human umbilical venular endothelial cells with thrombin induced rapid
      association of PKC-alpha with Rho. Activated PKC-alpha but not PKC-epsilon
      induced marked phosphorylation of GDI in vitro. Taken together, these results
      indicate that PKC-alpha is critical in regulating GDI phosphorylation, Rho
      activation, and in signaling Rho-dependent endothelial barrier dysfunction.

PMID- 11309398
TI  - Distinction between major and minor Bacillus signal peptidases based on
      phylogenetic and structural criteria.
AB  - The processing of secretory preproteins by signal peptidases (SPases) is
      essential for cell viability. As previously shown for Bacillus subtilis, only
      certain SPases of organisms containing multiple paralogous SPases are essential.
      This allows a distinction between SPases that are of major and minor importance
      for cell viability. Notably, the functional difference between major and minor
      SPases is not reflected clearly in sequence alignments. Here, we have
      successfully used molecular phylogeny to predict major and minor SPases. The
      results were verified with SPases from various bacilli. As predicted, the latter
      enzymes behaved as major or minor SPases when expressed in B. subtilis.
      Strikingly, molecular modeling indicated that the active site geometry is not a
      critical parameter for the classification of major and minor Bacillus SPases.
      Even though the substrate binding site of the minor SPase SipV is smaller than
      that of other known SPases, SipV could be converted into a major SPase without
      changing this site. Instead, replacement of amino-terminal residues of SipV with
      corresponding residues of the major SPase SipS was sufficient for conversion of
      SipV into a major SPase. This suggests that differences between major and minor
      SPases are based on activities other than substrate cleavage site selection.

PMID- 11309399
TI  - ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux
      regulatory protein.
AB  - ABCA1, an ATP-binding cassette transporter mutated in Tangier disease, promotes
      cellular phospholipid and cholesterol efflux by loading free apoA-I with these
      lipids. This process involves binding of apoA-I to the cell surface and
      phospholipid translocation by ABCA1. The goals of this study were to examine the
      relationship between ABCA1-mediated lipid efflux and apolipoprotein binding and
      to determine whether phospholipid and cholesterol efflux are coupled. Inhibition
      of lipid efflux by glybenclamide treatment or by mutation of the ATP-binding
      cassette of ABCA1 showed a close correlation between lipid efflux, the binding of
      apoA-I to cells, and cross-linking of apoA-I to ABCA1. The data suggest that a
      functionally important apoA-I binding site exists on ABCA1 and that the binding
      site could also involve lipids. After using cyclodextrin preincubation to deplete
      cellular cholesterol, ABCA1-mediated cholesterol efflux was abolished but
      phospholipid efflux and the binding of apoA-I were unaffected. The conditioned
      media from cyclodextrin-pretreated, ABCA1-expressing cells readily promoted
      cholesterol efflux when added to fresh cells not expressing ABCA1, indicating
      that cholesterol efflux can be dissociated from phospholipid efflux. Further,
      using a photoactivatable cholesterol analog, we showed that ABCA1 did not bind
      cholesterol directly, even though several other cholesterol-binding proteins
      specifically bound the cholesterol analog. The data suggest that the binding of
      apoA-I to ABCA1 leads to the formation of phospholipid-apoA-I complexes, which
      subsequently promote cholesterol efflux in an autocrine or paracrine fashion.

PMID- 11309400
TI  - Effects of 3' terminus modifications on mRNA functional decay during in vitro
      protein synthesis.
AB  - The pcnB gene, which encodes the principal poly(A) polymerase of Escherichia
      coli, promotes 3'-polyadenylation and chemical decay of mRNA. However, there is
      no evidence that pcnB-mediated mRNA destabilization decreases protein synthesis,
      suggesting that polyadenylation may enhance translational efficiency. Using in
      vitro translation by E. coli cell extracts and toeprinting analysis of
      transcripts encoded by the chloramphenicol acetyltransferase (CAT) and beta
      galactosidase genes to investigate this notion, we found no effect of poly(A)
      tails on protein synthesis. However, we observed that 3'-polyguanylation delayed
      the chemical decay of CAT mRNA and, even more dramatically, increased the ability
      of CAT mRNA to produce enzymatically active full-length protein in 30 S E. coli
      cell fractions. This resulted from interference with the primary mechanism for
      inactivation of CAT transcript function in cell extracts, which occurred by 3'
      exonucleolytic degradation rather than endonucleolytic fragmentation by RNase E.
      Using bacteriophage T7 RNA polymerase to install poly(G) tails on mRNAs
      transcribed from polymerase chain reaction-generated DNA templates, we observed
      sharply increased synthesis of active proteins in vitro in coupled
      transcription/translation reactions. The ability of poly(G) tails to functionally
      stabilize transcripts from polymerase chain reaction-generated templates allows
      proteins encoded by translational open reading frames on genomic DNA or cDNA to
      be synthesized directly and efficiently in vitro.

PMID- 11309401
TI  - The use of transgenic mice to analyze the role of accessory factor two in the
      regulation of phosphoenolpyruvate carboxykinase (GTP) gene transcription during
      diabetes.
AB  - The regulation of transcription of the gene for the cytosolic form of
      phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (4.1.1.32) during diabetes is a
      complex process that involves a number of regulatory elements in the PEPCK-C gene
      promoter. The accessory factor 2 (AF2)-binding region that is contained within
      the glucocorticoid regulatory unit of the PEPCK-C gene promoter (-451 to -353)
      has been implicated in the action of both insulin and glucocorticoids on PEPCK-C
      gene transcription. To determine the role of AF2 in these processes, we have
      generated a mouse model bearing a transgene that contains the PEPCK-C gene
      promoter with a mutation in the AF2-binding region. This promoter is linked to
      the structural gene for human growth hormone that is biologically inactive (AF2
      2000/hGx). In the absence of the AF2 regulatory element, the transcription of the
      transgene in the liver is not induced by diabetes but is inhibited by the
      administration of insulin. There is also a marked reduction in the response of
      the AF2-2000/hGx gene in the kidney to the administration of glucocorticoids. The
      AF2-2000/hGx gene in the liver responds normally to a high carbohydrate diet with
      a marked decrease in gene transcription. This suggests that insulin is not
      exerting its usual negative effect on the PEPCK-C gene promoter through the AF2
      site. In contrast, the response of this transgene to a high fat/carbohydrate-free
      diet is severely blunted. Our results support a role for the AF2 site in the
      PEPCK-C gene promoter in the effect of glucocorticoids, but not insulin, on PEPCK
      C gene transcription in the liver.

PMID- 11309402
TI  - A conserved alpha-helix at the amino terminus of prosomatostatin serves as a
      sorting signal for the regulated secretory pathway.
AB  - Mammalian prosomatostatin (PSST) contains the bioactive peptides SST-14 and SST
      28 at the COOH-terminal end of the molecule and a putative sorting signal in the
      propeptide segment for targeting the precursor to the regulated secretory
      pathway. The NH(2)-terminal segment of PSST consists of an amphipathic alpha
      helix, which has been totally conserved throughout vertebrate evolution. We have
      analyzed the PSST-(3--15) region for sorting function by alanine scanning and
      deletional mutagenesis. Mutants created were stably expressed in AtT-20 cells.
      Regulated secretion was studied by analyzing basal and stimulated release of SST
      14 LI and by immunocytochemistry for staining of SST-14 LI in punctate granules.
      Deletion of the PSST-(3--15) segment blocked regulated secretion and rerouted
      PSST for constitutive secretion as unprocessed precursor. Alanine scanning
      mutagenesis identified the region Pro(5)--Gln(12) as being important in precursor
      targeting, with Leu(7) and Leu(11) being critical. Molecular modeling
      demonstrated that these two residues are located in close proximity on a
      hydrophobic surface of the alpha-helix. Disruption of the alpha-helix did not
      impair the ability of PSST to be processed at the COOH terminus to SST-14 and SST
      28. Processing, however, was shifted to the early compartments of the secretory
      pathway rather than storage granules and was relatively inefficient.

PMID- 11309403
TI  - Secondary substrate-binding exosite in the serine protease domain of activated
      protein C important for cleavage at Arg-506 but not at Arg-306 in factor Va.
AB  - Proteolytic inactivation of activated factor V (FVa) by activated protein C (APC)
      is a key reaction in the regulation of hemostasis. We now demonstrate the
      importance of a positive cluster in loop 37 of the serine protease (SP) domain of
      APC for the degradation of FVa. Lysine residues in APC at positions 37, 38, and
      39 form a secondary binding site for FVa, which is important for cleavage of FVa
      at Arg-506 while having no effect on Arg-306 cleavage. In contrast, topological
      neighbors Lys-62, Lys-63, and Arg-74 in APC appear of minor importance in FVa
      degradation. This demonstrates that secondary binding exosites of APC
      specifically guide the proteolytic action of APC, resulting in a more favorable
      degradation of the 506-507 peptide bond as compared with the 306-307 bond.

PMID- 11309404
TI  - The yeast cell wall and septum as paradigms of cell growth and morphogenesis.

PMID- 11309405
TI  - Psychosine, cytokinesis, and orphan receptors. Unexpected connections.

PMID- 11309406
TI  - Desmoglein isoform distribution affects stratum corneum structure and function.
AB  - Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In
      stratified squamous epithelia there are two major isoforms of desmoglein, 1 and
      3, with different distributions in epidermis and mucous membrane. Since either
      desmoglein isoform alone can mediate adhesion, the reason for their differential
      distribution is not known. To address this issue, we engineered transgenic mice
      with desmoglein 3 under the control of the involucrin promoter. These mice
      expressed desmoglein 3 with the same distribution in epidermis as found in normal
      oral mucous membranes, while expression of other major differentiation molecules
      was unchanged. Although the nucleated epidermis appeared normal, the epidermal
      stratum corneum was abnormal with gross scaling, and a lamellar histology
      resembling that of normal mucous membrane. The mice died shortly after birth with
      severe dehydration, suggesting excessive transepidermal water loss, which was
      confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum
      corneum showed premature loss of cohesion of corneocytes. This dysadhesion of
      corneocytes and its contribution to increased transepidermal water loss was
      confirmed by tape stripping. These data demonstrate that differential expression
      of desmoglein isoforms affects the major function of epidermis, the permeability
      barrier, by altering the structure of the stratum corneum.

PMID- 11309407
TI  - Nuclear import of histone H2A and H2B is mediated by a network of karyopherins.
AB  - The first step in the assembly of new chromatin is the cell cycle-regulated
      synthesis and nuclear import of core histones. The core histones include H2A and
      H2B, which are assembled into nucleosomes as heterodimers. We show here that the
      import of histone H2A and H2B is mediated by several members of the karyopherin
      (Kap; importin) family. An abundant complex of H2A, H2B, and Kap114p was detected
      in cytosol. In addition, two other Kaps, Kap121p and Kap123p, and the histone
      chaperone Nap1p were isolated with H2A and H2B. Nap1p is not necessary for the
      formation of the Kap114p-H2A/H2B complex or for import of H2A and H2B. We
      demonstrate that both histones contain a nuclear localization sequence (NLS) in
      the amino-terminal tail. Fusions of the NLSs to green fluorescent protein were
      specifically mislocalized to the cytoplasm in kap mutant strains. In addition, we
      detected a specific mislocalization in a kap95 temperature-sensitive strain,
      suggesting that this Kap is also involved in the import of H2A and H2B in vivo.
      Importantly, we show that Kap114p, Kap121p, and Kap95 interact directly with both
      histone NLSs and that RanGTP inhibits this association. These data suggest that
      the import of H2A and H2B is mediated by a network of Kaps, in which Kap114p may
      play the major role.

PMID- 11309408
TI  - Conversion of zonulae occludentes from tight to leaky strand type by introducing
      claudin-2 into Madin-Darby canine kidney I cells.
AB  - There are two strains of MDCK cells, MDCK I and II. MDCK I cells show much higher
      transepithelial electric resistance (TER) than MDCK II cells, although they bear
      similar numbers of tight junction (TJ) strands. We examined the expression
      pattern of claudins, the major components of TJ strands, in these cells: claudin
      1 and -4 were expressed both in MDCK I and II cells, whereas the expression of
      claudin-2 was restricted to MDCK II cells. The dog claudin-2 cDNA was then
      introduced into MDCK I cells to mimic the claudin expression pattern of MDCK II
      cells. Interestingly, the TER values of MDCK I clones stably expressing claudin-2
      (dCL2-MDCK I) fell to the levels of MDCK II cells (>20-fold decrease). In
      contrast, when dog claudin-3 was introduced into MDCK I cells, no change was
      detected in their TER. Similar results were obtained in mouse epithelial cells,
      Eph4. Morphometric analyses identified no significant differences in the density
      of TJs or in the number of TJ strands between dCL2-MDCK I and control MDCK I
      cells. These findings indicated that the addition of claudin-2 markedly decreased
      the tightness of individual claudin-1/4-based TJ strands, leading to the
      speculation that the combination and mixing ratios of claudin species determine
      the barrier properties of individual TJ strands.

PMID- 11309409
TI  - Integrin-mediated adhesion regulates ERK nuclear translocation and
      phosphorylation of Elk-1.
AB  - Integrin-mediated adhesion to the extracellular matrix permits efficient growth
      factor-mediated activation of extracellular signal-regulated kinases (ERKs).
      Points of regulation have been localized to the level of receptor phosphorylation
      or to activation of the downstream components, Raf and MEK (mitogen-activated
      protein kinase/ERK kinase). However, it is also well established that ERK
      translocation from the cytoplasm to the nucleus is required for G1 phase cell
      cycle progression. Here we show that phosphorylation of the nuclear ERK
      substrate, Elk-1 at serine 383, is anchorage dependent in response to growth
      factor treatment of NIH 3T3 fibroblasts. Furthermore, when we activated ERK in
      nonadherent cells by expression of active components of the ERK cascade,
      subsequent phosphorylation of Elk-1 at serine 383 and Elk-1-mediated
      transactivation were still impaired compared with adherent cells. Elk-1
      phosphorylation was dependent on an intact actin cytoskeleton, as discerned by
      treatment with cytochalasin D (CCD). Finally, expression of active MEK failed to
      predominantly localize ERK to the nucleus in suspended cells or adherent cells
      treated with CCD. These data show that integrin-mediated organization of the
      actin cytoskeleton regulates localization of activated ERK, and in turn the
      ability of ERK to efficiently phosphorylate nuclear substrates.

PMID- 11309410
TI  - Identities of sequestered proteins in aggregates from cells with induced
      polyglutamine expression.
AB  - Proteins with expanded polyglutamine (polyQ) tracts have been linked to
      neurodegenerative diseases. One common characteristic of expanded-polyQ
      expression is the formation of intracellular aggregates (IAs). IAs purified from
      polyQ-expressing cells were dissociated and studied by protein blot assay and
      mass spectrometry to determine the identity, condition, and relative level of
      several proteins sequestered within aggregates. Most of the sequestered proteins
      comigrated with bands from control extracts, indicating that the sequestered
      proteins were intact and not irreversibly bound to the polyQ polymer. Among the
      proteins found sequestered at relatively high levels in purified IAs were
      ubiquitin, the cell cycle-regulating proteins p53 and mdm-2, HSP70, the global
      transcriptional regulator Tata-binding protein/TFIID, cytoskeleton proteins actin
      and 68-kD neurofilament, and proteins of the nuclear pore complex. These data
      reveal that IAs are highly complex structures with a multiplicity of contributing
      proteins.

PMID- 11309411
TI  - OSP/claudin-11 forms a complex with a novel member of the tetraspanin super
      family and beta1 integrin and regulates proliferation and migration of
      oligodendrocytes.
AB  - Oligodendrocyte-specific protein (OSP)/claudin-11 is a major component of central
      nervous system myelin and forms tight junctions (TJs) within myelin sheaths. TJs
      are essential for forming a paracellular barrier and have been implicated in the
      regulation of growth and differentiation via signal transduction pathways. We
      have identified an OSP/claudin-11-associated protein (OAP)1, using a yeast two
      hybrid screen. OAP-1 is a novel member of the tetraspanin superfamily, and it is
      widely expressed in several cell types, including oligodendrocytes. OAP-1,
      OSP/claudin-11, and beta1 integrin form a complex as indicated by
      coimmunoprecipitation and confocal immunocytochemistry. Overexpression of
      OSP/claudin-11 or OAP-1 induced proliferation in an oligodendrocyte cell line.
      Anti-OAP-1, anti-OSP/claudin-11, and anti-beta1 integrin antibodies inhibited
      migration of primary oligodendrocytes, and migration was impaired in OSP/claudin
      11-deficient primary oligodendrocytes. These data suggest a role for OSP/claudin
      11, OAP-1, and beta1 integrin complex in regulating proliferation and migration
      of oligodendrocytes, a process essential for normal myelination and repair.

PMID- 11309412
TI  - An exclusively nuclear RNA-binding protein affects asymmetric localization of
      ASH1 mRNA and Ash1p in yeast.
AB  - The localization of ASH1 mRNA to the distal tip of budding yeast cells is
      essential for the proper regulation of mating type switching in Saccharomyces
      cerevisiae. A localization element that is predominantly in the 3'-untranslated
      region (UTR) can direct this mRNA to the bud. Using this element in the three
      hybrid in vivo RNA-binding assay, we identified a protein, Loc1p, that binds in
      vitro directly to the wild-type ASH1 3'-UTR RNA, but not to a mutant RNA
      incapable of localizing to the bud nor to several other mRNAs. LOC1 codes for a
      novel protein that recognizes double-stranded RNA structures and is required for
      efficient localization of ASH1 mRNA. Accordingly, Ash1p gets symmetrically
      distributed between daughter and mother cells in a loc1 strain. Surprisingly,
      Loc1p was found to be strictly nuclear, unlike other known RNA-binding proteins
      involved in mRNA localization which shuttle between the nucleus and the
      cytoplasm. We propose that efficient cytoplasmic ASH1 mRNA localization requires
      a previous interaction with specific nuclear factors.

PMID- 11309413
TI  - Cytochrome c maintains mitochondrial transmembrane potential and ATP generation
      after outer mitochondrial membrane permeabilization during the apoptotic process.
AB  - During apoptosis, cytochrome c is released into the cytosol as the outer membrane
      of mitochondria becomes permeable, and this acts to trigger caspase activation.
      The consequences of this release for mitochondrial metabolism are unclear. Using
      single-cell analysis, we found that when caspase activity is inhibited,
      mitochondrial outer membrane permeabilization causes a rapid depolarization of
      mitochondrial transmembrane potential, which recovers to original levels over the
      next 30-60 min and is then maintained. After outer membrane permeabilization,
      mitochondria can use cytoplasmic cytochrome c to maintain mitochondrial
      transmembrane potential and ATP production. Furthermore, both cytochrome c
      release and apoptosis proceed normally in cells in which mitochondria have been
      uncoupled. These studies demonstrate that cytochrome c release does not affect
      the integrity of the mitochondrial inner membrane and that, in the absence of
      caspase activation, mitochondrial functions can be maintained after the release
      of cytochrome c.

PMID- 11309414
TI  - Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent
      pathway.
AB  - The nuclear factor of activated T cells (NFAT) family of transcription factors
      regulates the development and differentiation of several tissue types. Here, we
      examine the role of NFATC2 in skeletal muscle by analyzing adult NFATC2(-/)-
      mice. These mice exhibit reduced muscle size due to a decrease in myofiber cross
      sectional area, suggesting that growth is blunted. Muscle growth was examined
      during regeneration after injury, wherein NFATC2-null myofibers form normally but
      display impaired growth. The growth defect is intrinsic to muscle cells, since
      the lack of NFATC2 in primary muscle cultures results in reduced cell size and
      myonuclear number in myotubes. Retroviral-mediated expression of NFATC2 in the
      mutant cells rescues this cellular phenotype. Myonuclear number is similarly
      decreased in NFATC2(-/)- mice. Taken together, these results implicate a novel
      role for NFATC2 in skeletal muscle growth. We demonstrate that during growth of
      multinucleated muscle cells, myoblasts initially fuse to form myotubes with a
      limited number of nuclei and that subsequent nuclear addition and increases in
      myotube size are controlled by a molecular pathway regulated by NFATC2.

PMID- 11309415
TI  - Microdomains of high calcium are not required for exocytosis in RBL-2H3 mucosal
      mast cells.
AB  - We have previously shown that store-associated microdomains of high Ca(2+) are
      not essential for exocytosis in RBL-2H3 mucosal mast cells. We have now examined
      whether Ca(2+) microdomains near the plasma membrane are required, by comparing
      the secretory responses seen when Ca(2+) influx was elicited by two very
      different mechanisms. In the first, antigen was used to activate the Ca(2+)
      release-activated Ca(2+) (CRAC) current (I(CRAC)) through CRAC channels. In the
      second, a Ca(2+) ionophore was used to transport Ca(2+) randomly across the
      plasma membrane. Since store depletion by Ca(2+) ionophore will also activate
      I(CRAC), different means of inhibiting I(CRAC) before ionophore addition were
      used. Ca(2+) responses and secretion in individual cells were compared using
      simultaneous indo-1 microfluorometry and constant potential amperometry.
      Secretion still takes place when the increase in intracellular Ca(2+) occurs
      diffusely via the Ca(2+) ionophore, and at an average intracellular Ca(2)+
      concentration that is no greater than that observed when Ca(2+) entry via CRAC
      channels triggers secretion. Our results suggest that microdomains of high Ca(2+)
      near the plasma membrane, or associated with mitochondria or Ca(2+) stores, are
      not required for secretion. Therefore, we conclude that modest global increases
      in intracellular Ca(2+) are sufficient for exocytosis in these nonexcitable
      cells.

PMID- 11309416
TI  - Mammalian Abp1, a signal-responsive F-actin-binding protein, links the actin
      cytoskeleton to endocytosis via the GTPase dynamin.
AB  - The actin cytoskeleton has been implicated in endocytosis, yet few molecular
      links to the endocytic machinery have been established. Here we show that the
      mammalian F-actin-binding protein Abp1 (SH3P7/HIP-55) can functionally link the
      actin cytoskeleton to dynamin, a GTPase that functions in endocytosis. Abp1 binds
      directly to dynamin in vitro through its SH3 domain. Coimmunoprecipitation and
      colocalization studies demonstrated the in vivo relevance of this interaction. In
      neurons, mammalian Abp1 and dynamin colocalized at actin-rich sites proximal to
      the cell body during synaptogenesis. In fibroblasts, mAbp1 appeared at dynamin
      rich sites of endocytosis upon growth factor stimulation. To test whether Abp1
      functions in endocytosis, we overexpressed several Abp1 constructs in Cos-7 cells
      and assayed receptor-mediated endocytosis. While overexpression of Abp1's actin
      binding modules did not interfere with endocytosis, overexpression of the SH3
      domain led to a potent block of transferrin uptake. This implicates the
      Abp1/dynamin interaction in endocytic function. The endocytosis block was rescued
      by cooverexpression of dynamin. Since the addition of the actin-binding modules
      of Abp1 to the SH3 domain construct also fully restored endocytosis, Abp1 may
      support endocytosis by combining its SH3 domain interactions with cytoskeletal
      functions in response to signaling cascades converging on this linker protein.

PMID- 11309417
TI  - Regulation and localization of the Bloom syndrome protein in response to DNA
      damage.
AB  - Bloom syndrome (BS) is an autosomal recessive disorder characterized by a high
      incidence of cancer and genomic instability. BLM, the protein defective in BS, is
      a RecQ-like helicase, presumed to function in DNA replication, recombination, or
      repair. BLM localizes to promyelocytic leukemia protein (PML) nuclear bodies and
      is expressed during late S and G2. We show, in normal human cells, that the
      recombination/repair proteins hRAD51 and replication protein (RP)-A assembled
      with BLM into a fraction of PML bodies during late S/G2. Biochemical experiments
      suggested that BLM resides in a nuclear matrix-bound complex in which association
      with hRAD51 may be direct. DNA-damaging agents that cause double strand breaks
      and a G2 delay induced BLM by a p53- and ataxia-telangiectasia mutated
      independent mechanism. This induction depended on the G2 delay, because it failed
      to occur when G2 was prevented or bypassed. It coincided with the appearance of
      foci containing BLM, PML, hRAD51 and RP-A, which resembled ionizing radiation
      induced foci. After radiation, foci containing BLM and PML formed at sites of
      single-stranded DNA and presumptive repair in normal cells, but not in cells with
      defective PML. Our findings suggest that BLM is part of a dynamic nuclear matrix
      based complex that requires PML and functions during G2 in undamaged cells and
      recombinational repair after DNA damage.

PMID- 11309418
TI  - Cvt9/Gsa9 functions in sequestering selective cytosolic cargo destined for the
      vacuole.
AB  - Three overlapping pathways mediate the transport of cytoplasmic material to the
      vacuole in Saccharomyces cerevisiae. The cytoplasm to vacuole targeting (Cvt)
      pathway transports the vacuolar hydrolase, aminopeptidase I (API), whereas
      pexophagy mediates the delivery of excess peroxisomes for degradation. Both the
      Cvt and pexophagy pathways are selective processes that specifically recognize
      their cargo. In contrast, macroautophagy nonselectively transports bulk cytosol
      to the vacuole for recycling. Most of the import machinery characterized thus far
      is required for all three modes of transport. However, unique features of each
      pathway dictate the requirement for additional components that differentiate
      these pathways from one another, including at the step of specific cargo
      selection.We have identified Cvt9 and its Pichia pastoris counterpart Gsa9. In S.
      cerevisiae, Cvt9 is required for the selective delivery of precursor API (prAPI)
      to the vacuole by the Cvt pathway and the targeted degradation of peroxisomes by
      pexophagy. In P. pastoris, Gsa9 is required for glucose-induced pexophagy.
      Significantly, neither Cvt9 nor Gsa9 is required for starvation-induced
      nonselective transport of bulk cytoplasmic cargo by macroautophagy. The deletion
      of CVT9 destabilizes the binding of prAPI to the membrane and analysis of a cvt9
      temperature-sensitive mutant supports a direct role of Cvt9 in transport vesicle
      formation. Cvt9 oligomers peripherally associate with a novel, perivacuolar
      membrane compartment and interact with Apg1, a Ser/Thr kinase essential for both
      the Cvt pathway and autophagy. In P. pastoris Gsa9 is recruited to concentrated
      regions on the vacuole membrane that contact peroxisomes in the process of being
      engulfed by pexophagy. These biochemical and morphological results demonstrate
      that Cvt9 and the P. pastoris homologue Gsa9 may function at the step of
      selective cargo sequestration.

PMID- 11309419
TI  - A mechanism for nuclear positioning in fission yeast based on microtubule
      pushing.
AB  - The correct positioning of the nucleus is often important in defining the spatial
      organization of the cell, for example, in determining the cell division plane. In
      interphase Schizosaccharomyces pombe cells, the nucleus is positioned in the
      middle of the cylindrical cell in an active microtubule (MT)-dependent process.
      Here, we used green fluorescent protein markers to examine the dynamics of MTs,
      spindle pole body, and the nuclear envelope in living cells. We find that
      interphase MTs are organized in three to four antiparallel MT bundles arranged
      along the long axis of the cell, with MT plus ends facing both the cell tips and
      minus ends near the middle of the cell. The MT bundles are organized from medial
      MT-organizing centers that may function as nuclear attachment sites. When MTs
      grow to the cell tips, they exert transient forces produced by plus end MT
      polymerization that push the nucleus. After an average of 1.5 min of growth at
      the cell tip, MT plus ends exhibit catastrophe and shrink back to the nuclear
      region before growing back to the cell tip. Computer modeling suggests that a
      balance of these pushing MT forces can provide a mechanism to position the
      nucleus at the middle of the cell.

PMID- 11309420
TI  - Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z
      disc and I-band protein assemblies.
AB  - We describe here a novel sarcomeric 145-kD protein, myopalladin, which tethers
      together the COOH-terminal Src homology 3 domains of nebulin and nebulette with
      the EF hand motifs of alpha-actinin in vertebrate Z-lines. Myopalladin's
      nebulin/nebulette and alpha-actinin-binding sites are contained in two distinct
      regions within its COOH-terminal 90-kD domain. Both sites are highly homologous
      with those found in palladin, a protein described recently required for actin
      cytoskeletal assembly (Parast, M.M., and C.A. Otey. 2000. J. Cell Biol. 150:643
      656). This suggests that palladin and myopalladin may have conserved roles in
      stress fiber and Z-line assembly. The NH(2)-terminal region of myopalladin
      specifically binds to the cardiac ankyrin repeat protein (CARP), a nuclear
      protein involved in control of muscle gene expression. Immunofluorescence and
      immunoelectron microscopy studies revealed that myopalladin also colocalized with
      CARP in the central I-band of striated muscle sarcomeres. Overexpression of
      myopalladin's NH(2)-terminal CARP-binding region in live cardiac myocytes
      resulted in severe disruption of all sarcomeric components studied, suggesting
      that the myopalladin-CARP complex in the central I-band may have an important
      regulatory role in maintaining sarcomeric integrity. Our data also suggest that
      myopalladin may link regulatory mechanisms involved in Z-line structure (via
      alpha-actinin and nebulin/nebulette) to those involved in muscle gene expression
      (via CARP).

PMID- 11309421
TI  - Identification of a molecular target of psychosine and its role in globoid cell
      formation.
AB  - Globoid cell leukodystrophy (GLD) is characterized histopathologically by
      apoptosis of oligodendrocytes, progressive demyelination, and the existence of
      large, multinuclear (globoid) cells derived from perivascular microglia. The
      glycosphingolipid, psychosine (d-galactosyl-beta-1,1' sphingosine), accumulates
      to micromolar levels in GLD patients who lack the degradative enzyme galactosyl
      ceramidase. Here we document that an orphan G protein-coupled receptor, T cell
      death-associated gene 8, is a specific psychosine receptor. Treatment of cultured
      cells expressing this receptor with psychosine or structurally related
      glycosphingolipids results in the formation of globoid, multinuclear cells. Our
      discovery of a molecular target for psychosine suggests a mechanism for the
      globoid cell histology characteristic of GLD, provides a tool with which to
      explore the disjunction of mitosis and cytokinesis in cell cultures, and provides
      a platform for developing a medicinal chemistry for psychosine.

PMID- 11309422
TI  - Stu2 promotes mitotic spindle elongation in anaphase.
AB  - During anaphase, mitotic spindles elongate up to five times their metaphase
      length. This process, known as anaphase B, is essential for correct segregation
      of chromosomes. Here, we examine the control of spindle length during anaphase in
      the budding yeast Saccharomyces cerevisiae. We show that microtubule
      stabilization during anaphase requires the microtubule-associated protein Stu2.
      We further show that the activity of Stu2 is opposed by the activity of the
      kinesin-related protein Kip3. Reexamination of the kinesin homology tree suggests
      that KIP3 is the S. cerevisiae orthologue of the microtubule-destabilizing
      subfamily of kinesins (Kin I). We conclude that a balance of activity between
      evolutionally conserved microtubule-stabilizing and microtubule-destabilizing
      factors is essential for correct spindle elongation during anaphase B.

PMID- 11309425
TI  - Intravesical therapy for bladder cancer: empiricism at the helm.

PMID- 11309423
TI  - Flagellar radial spoke protein 3 is an A-kinase anchoring protein (AKAP).
AB  - Previous physiological and pharmacological experiments have demonstrated that the
      Chlamydomonas flagellar axoneme contains a cAMP-dependent protein kinase (PKA)
      that regulates axonemal motility and dynein activity. However, the mechanism for
      anchoring PKA in the axoneme is unknown. Here we test the hypothesis that the
      axoneme contains an A-kinase anchoring protein (AKAP). By performing RII blot
      overlays on motility mutants defective for specific axonemal structures, two
      axonemal AKAPs have been identified: a 240-kD AKAP associated with the central
      pair apparatus, and a 97-kD AKAP located in the radial spoke stalk. Based on a
      detailed analysis, we have shown that AKAP97 is radial spoke protein 3 (RSP3). By
      expressing truncated forms of RSP3, we have localized the RII-binding domain to a
      region between amino acids 144-180. Amino acids 161-180 are homologous with the
      RII-binding domains of other AKAPs and are predicted to form an amphipathic
      helix. Amino acid substitution of the central residues of this region (L to P or
      VL to AA) results in the complete loss of RII binding. RSP3 is located near the
      inner arm dyneins, where an anchored PKA would be in direct position to modify
      dynein activity and regulate flagellar motility.

PMID- 11309426
TI  - IOM report sets policy priorities for improving breast cancer screening.

PMID- 11309427
TI  - Chemoprevention: can industry and academia collaborate?

PMID- 11309429
TI  - U.K. charity focuses on treatment for teenagers.

PMID- 11309431
TI  - Better assays needed for hormone receptor status, experts say.

PMID- 11309432
TI  - Consensus on colorectal screening still difficult to achieve.

PMID- 11309434
TI  - Scientists report new finding in development of B cells.

PMID- 11309435
TI  - Guidelines 2000 for colon and rectal cancer surgery.
AB  - BACKGROUND: Oncologic resection techniques affect outcome for colon cancer and
      rectal cancer, but standardized guidelines have not been adopted. The National
      Cancer Institute sponsored a panel of experts to systematically review current
      literature and to draft guidelines that provide uniform definitions, principles,
      and practices. METHODS: Methods were similar to those described by the American
      Society of Clinical Oncology in developing practice guidelines. Experts
      representing oncology and surgery met to review current literature on oncologic
      resection techniques for level of evidence (I-V, where I is the best evidence and
      V is the least compelling) and grade of recommendation (A-D, where A is based on
      the best evidence and D is based on the weakest evidence). Initial guidelines
      were drafted, reviewed, and accepted by consensus. RESULTS: For the following
      seven factors, the level of evidence was II, III, or IV, and the findings were
      generally consistent (grade B): anatomic definition of colon versus rectum, tumor
      node-metastasis staging, radial margins, adjuvant R0 stage, inadvertent rectal
      perforation, distal and proximal rectal margins, and en bloc resection of
      adherent tumors. For another seven factors, the level of evidence was II, III, or
      IV, but findings were inconsistent (grade C): laparoscopic colectomy; colon
      lymphadenectomy; level of proximal vessel ligation, mesorectal excision, and
      extended lateral pelvic lymph node dissection (all three for rectal cancer); no
      touch technique; and bowel washout. For the other four factors, there was little
      or no systematic empirical evidence (grade D): abdominal exploration,
      oophorectomy, extent of colon resection, and total length of rectum resected.
      CONCLUSIONS: The panel reports surgical guidelines and definitions based on the
      best available evidence. The availability of more standardized information in the
      future should allow for more grade A recommendations.

PMID- 11309436
TI  - Methods to improve efficacy of intravesical mitomycin C: results of a randomized
      phase III trial.
AB  - BACKGROUND: Intravesical chemotherapy (i.e., placement of the drug directly in
      the bladder) with mitomycin C is beneficial for patients with superficial bladder
      cancer who are at high risk of recurrence, but standard therapy is empirically
      based and patient response rates have been variable, in part because of
      inadequate drug delivery. We carried out a prospective, two-arm, randomized,
      multi-institutional phase III trial to test whether enhancing the drug's
      concentration in urine would improve its efficacy. METHODS: Patients with
      histologically proven transitional cell carcinoma and at high risk for recurrence
      were eligible for the trial. Patients in the optimized-treatment arm (n = 119)
      received a 40-mg dose of mitomycin C, pharmacokinetic manipulations to increase
      drug concentration by decreasing urine volume, and urine alkalinization to
      stabilize the drug. Patients in the standard-treatment arm (n = 111) received a
      20-mg dose without pharmacokinetic manipulations or urine alkalinization. Both
      treatments were given weekly for 6 weeks. Primary endpoints were recurrence and
      time to recurrence. Treatment outcome was examined by use of Kaplan-Meier
      analysis with log-rank tests. Statistical tests were two-sided. RESULTS: Patients
      in the two arms did not differ in demographics or history of intravesical
      therapy. Dysuria occurred more frequently in the optimized arm but did not lead
      to more frequent treatment termination. In an intent-to-treat analysis, patients
      in the optimized arm showed a longer median time to recurrence (29.1 months; 95%
      confidence interval [CI] = 14.0 to 44.2 months) and a greater recurrence-free
      fraction (41.0%; 95% CI = 30.9% to 51.1%) at 5 years than patients in the
      standard arm (11.8 months; 95% CI = 7.2 to 16.4 months) and 24.6% (95% CI = 14.9%
      to 34.3%) (P =.005, log-rank test for time to recurrence). Improvements were
      found in all risk groups defined by tumor stage, grade, focality, and recurrence.
      CONCLUSIONS: This study identified a pharmacologically optimized intravesical
      mitomycin C treatment with statistically significantly enhanced efficacy.

PMID- 11309437
TI  - Randomized phase III intergroup trial of isotretinoin to prevent second primary
      tumors in stage I non-small-cell lung cancer.
AB  - BACKGROUND: Promising data have suggested that retinoid chemoprevention may help
      to control second primary tumors (SPTs), recurrence, and mortality of stage I non
      small-cell lung cancer (NSCLC) patients. METHODS: We carried out a National
      Cancer Institute (NCI) Intergroup phase III trial (NCI #I91-0001) with 1166
      patients with pathologic stage I NSCLC (6 weeks to 3 years from definitive
      resection and no prior radiotherapy or chemotherapy). Patients were randomly
      assigned to receive a placebo or the retinoid isotretinoin (30 mg/day) for 3
      years in a double-blind fashion. Patients were stratified at randomization by
      tumor stage, histology, and smoking status. The primary endpoint (time to SPT)
      and the secondary endpoints (times to recurrence and death) were analyzed by log
      rank test and the Cox proportional hazards model. All statistical tests were two
      sided. RESULTS: After a median follow-up of 3.5 years, there were no
      statistically significant differences between the placebo and isotretinoin arms
      with respect to the time to SPTs, recurrences, or mortality. The unadjusted
      hazard ratio (HR) of isotretinoin versus placebo was 1.08 (95% confidence
      interval [CI] = 0.78 to 1.49) for SPTs, 0.99 (95% CI = 0.76 to 1.29) for
      recurrence, and 1.07 (95% CI = 0.84 to 1.35) for mortality. Multivariate analyses
      showed that the rate of SPTs was not affected by any stratification factor. Rate
      of recurrence was affected by tumor stage (HR for T(2) versus T(1) = 1.77 [95% CI
      = 1.35 to 2.31]) and a treatment-by-smoking interaction (HR for treatment-by
      current-versus-never-smoking status = 3.11 [95% CI = 1.00 to 9.71]). Mortality
      was affected by tumor stage (HR for T(2) versus T(1) = 1.39 [95% CI = 1.10 to
      1.77]), histology (HR for squamous versus nonsquamous = 1.31 [95% CI = 1.03 to
      1.68]), and a treatment-by-smoking interaction (HR for treatment-by-current
      versus-never-smoking = 4.39 [95% CI = 1.11 to 17.29]). Mucocutaneous toxicity
      (P<.001) and noncompliance (40% versus 25% at 3 years) were higher in the
      isotretinoin arm than in the placebo arm. CONCLUSIONS: Isotretinoin treatment did
      not improve the overall rates of SPTs, recurrences, or mortality in stage I
      NSCLC. Secondary multivariate and subset analyses suggested that isotretinoin was
      harmful in current smokers and beneficial in never smokers.

PMID- 11309438
TI  - Second malignant neoplasms in five-year survivors of childhood cancer: childhood
      cancer survivor study.
AB  - BACKGROUND: Because survival rates among childhood cancer patients are
      increasing, assessing the risk of second and subsequent malignant neoplasms
      (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort,
      we identified the risk of SMNS: METHODS: A retrospective cohort of 13 581
      children diagnosed with common cancers before age 21 years and surviving at least
      5 years was constructed with the use of data from patients treated at 25 U.S. and
      Canadian institutions. SMNs were ascertained through self-administered
      questionnaires and verified by pathology reports. Information on therapeutic
      exposures was abstracted from medical records. The risk of SMN was evaluated by
      standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple
      regression models were used to assess the impact of host and therapy factors on
      the risk of developing SMNS: All statistical tests were two-sided. RESULTS: In
      298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval
      [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast
      cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to
      20.83], respectively). A statistically significant excess of SMNs followed all
      childhood cancers. In multivariate regression models adjusted for therapeutic
      radiation exposure, SMNs of any type were independently associated with female
      sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood
      Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and
      exposure to alkylating agents (P for trend =.02). Twenty years after the
      childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%.
      However, only 1.88 excess malignancies occurred per 1000 years of patient follow
      up. CONCLUSIONS: Success in treating children with cancer should not be
      overshadowed by the incidence of SMNS: However, patients and health-care
      providers must be aware of risk factors for SMNs so that surveillance is focused
      and early prevention strategies are implemented.

PMID- 11309439
TI  - Axillary lymph node staging in breast cancer by 2-fluoro-2-deoxy-D-glucose
      positron emission tomography: clinical evaluation and alternative management.
AB  - BACKGROUND: Surgical removal of axillary lymph node and histologic examination
      for metastases are used to determine whether adjuvant treatment is necessary for
      patients with breast cancer. Axillary lymph node dissection (ALND) is a costly
      procedure associated with various side effects, and 80% or more of patients with
      tumors of 20 mm or less are lymph node negative and might avoid ALND. In this
      study, we evaluated whether an alternative, noninvasive method--i.e., positron
      emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)-- could be
      used to determine axillary lymph node status in patients with breast cancer.
      METHODS: One hundred sixty-seven consecutive patients with breast cancers of 50
      mm or less (range = 5-50 mm; mean = 21 mm) scheduled for complete ALND were
      studied preoperatively with FDG-PET, and then PET and pathology results from ALND
      were compared. All statistical tests were two-sided. RESULTS: The overall
      sensitivity, specificity, and accuracy of lymph node staging with PET were 94.4%
      (PET detected 68 of 72 patients with axillary involvement; 95% confidence
      interval [CI] = 86.0% to 98.2%), 86.3% (82 of 95 patients without axillary
      involvement; 95% CI = 77.8% to 91.9%), and 89.8% (150 of 167 patients with breast
      cancer; 95% CI = 84.2% to 93.6%), respectively. Positive- and negative-predictive
      values were 84.0% (68 patients with histologically positive lymph nodes of 81
      patients with positive FDG-PET scan; 95% CI = 74.2% to 90.5%) and 95.3% (82
      patients with histologically negative lymph nodes of 86 patients with negative
      FDG-PET scan; 95% CI = 88.2% to 98.5%), respectively. When PET results for
      axillary metastasis were analyzed by tumor size, the diagnostic accuracy was
      similar for all groups (86.0%-94.2%), with higher sensitivity for tumors of 21-50
      mm (98.0%) and higher specificity for tumors of 10 mm or less (87.8%), and the
      range was 93.5%-97.3% for negative-predictive values and 54.5%-94.1% for positive
      predictive values. Among the 72 patients with axillary involvement, PET detected
      three or fewer metastatic lymph nodes in 27 (37.5%) patients, about 80% of whom
      had no clinically palpable axillary lymph nodes. CONCLUSIONS: Noninvasive FDG-PET
      appears to be an accurate technique to predict axillary status in patients with
      breast cancer and thus to identify patients who might avoid ALND. These results
      should be confirmed in large multicenter studies.

PMID- 11309440
TI  - Testing for colon neoplasia susceptibility variants at the human COX2 locus.
AB  - BACKGROUND: Siblings and other first-degree relatives of patients with "sporadic"
      (i.e., apparently nonfamilial) colorectal cancer or precursor adenomatous colon
      polyps have an increased risk of developing colon neoplasia. This observation
      suggests the presence of inherited genetic determinants for sporadic colon
      neoplasia. Mice homozygous for a null cyclooxygenase 2 (COX2) (also called PTGS2)
      allele have a dramatically reduced susceptibility to the development of
      intestinal adenomas. In humans, use of pharmacologic inhibitors of COX2 enzyme
      activity are associated with reduced risk of colon neoplasia. This study examined
      whether the human COX2 locus may be linked to colon neoplasia in humans. METHODS:
      We used the affected sibling-pair method to test for linkage of the human COX2
      locus to colon neoplasia. RESULTS: We examined 74 concordantly affected sibling
      pairs from 46 sibships with colon neoplasia. One hundred five siblings from these
      sibships were diagnosed with either colorectal cancer or colon adenomatous polyps
      before age 65 years. No linkage between COX2 and colon neoplasia was found by use
      of a multipoint model-free linkage analysis (estimate of allele sharing was 0.44;
      standard error = +/-0.04; 95% confidence interval = 0.36 to 0.52). Moreover, even
      allowing for heterogeneity, the potential that a COX2 colon neoplasia
      susceptibility variant was present within a substantial subset of these sibships
      was strongly excluded under either a recessive or a dominant inheritance model
      (95% confidence to exclude a model in which 2.7% or more of the sibling pairs
      harbor a dominant susceptibility allele). CONCLUSIONS: This study of concordantly
      affected sibling pairs thus demonstrates that variations in the COX2 gene are
      unlikely to be a source of individual susceptibility to colon neoplasia in
      humans.

PMID- 11309441
TI  - Familial risk of pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer-related
      mortality in the United STATES: Although smoking and age are known risk factors
      for pancreatic cancer, several case reports and case-control studies have
      suggested that there is also a familial risk. We evaluated whether a family
      history of pancreatic cancer increases the risk of pancreatic cancer in first
      degree relatives and whether smoking and younger age at cancer diagnosis further
      increase this risk. METHODS: We conducted in-person interviews with 247 patients
      ("case probands") with pancreatic cancer and 420 population-based control
      probands to collect risk factor data and pancreatic cancer family history for
      1816 first-degree relatives of the case probands and 3157 first-degree relatives
      of the control probands. We analyzed the data by unconditional logistic
      regression models, with adjustment for correlated data by use of generalized
      estimating equations. All statistical tests were two-sided. RESULTS: A positive
      family history of pancreatic cancer (i.e., being related to a case proband) or
      ever-smoking cigarettes approximately doubled the risk of pancreatic cancer
      (relative risk [RR] = 2.49; 95% confidence interval [CI] = 1.32 to 4.69; RR =
      2.04; 95% CI = 1.09 to 3.83, respectively). The RR increased to 8.23 (95% CI =
      2.18 to 31.07) for relatives who ever smoked and were related to a case proband
      who was diagnosed before age 60 years. CONCLUSION: Routine questioning of
      patients about a family history of pancreatic cancer, the age of onset of this
      cancer in their relatives, and the patient's smoking status may identify
      individuals at high risk of pancreatic cancer. Future research exploring the
      genetic and environmental interactions associated with the risk of pancreatic
      cancer is critically important.

PMID- 11309442
TI  - Maternal genetic effects on neonatal susceptibility to oxidative damage from
      environmental tobacco smoke.

PMID- 11309443
TI  - Radiofrequency ablation: a novel approach for treatment of metastatic
      pheochromocytoma.

PMID- 11309444
TI  - Re: plasma insulin-like growth factor-I, insulin-like growth factor-binding
      proteins, and prostate cancer risk: a prospective study.

PMID- 11309447
TI  - Re: characterization of hereditary nonpolyposis colorectal cancer families from a
      population-based series of cases.

PMID- 11309448
TI  - Progress in inflammatory myopathies: good but not good enough.

PMID- 11309449
TI  - Systematic review of immunomodulatory drugs for the treatment of people with
      multiple sclerosis: Is there good quality evidence on effectiveness and cost?
AB  - OBJECTIVE: To review the clinical effectiveness and costs of a range of disease
      modifying drugs in multiple sclerosis. Drugs included are azathioprine,
      cladribine, cyclophosphamide, intravenous immunoglobulin, methotrexate, and
      mitoxantrone. METHODS: Electronic databases and bibliographies of related papers
      were searched for randomised controlled trials (RCTs) and systematic reviews, and
      experts and pharmaceutical companies were contacted for further information.
      Inclusion and quality criteria were assessed, data extraction undertaken by one
      reviewer and checked by a second reviewer, with discrepancies being resolved
      through discussion. Costs were obtained and cost-effectiveness papers sought.
      RESULTS: Seventeen studies met the inclusion criteria for the review. Evidence
      for the clinical effectiveness of the drugs showed some reductions in relapse
      rates and/or progression to disability for people with MS, although benefits may
      be lessened by wide ranging side effects. Annual drug costs/patient are estimated
      to range from 60 pounds to 10200 pounds. No cost effectiveness studies were
      found. CONCLUSION: Evidence for the effectiveness of these drugs in multiple
      sclerosis is problematic because there are few good quality trials for each drug.
      Trials often have methodological limitations and use different treatment regimes,
      patient groups, and outcome measures. Well conducted trials using outcome
      measures with clinical significance for groups of patients with different types
      of multiple sclerosis and long term follow up are needed if the evidence base of
      treatment for the disease is to be improved.

PMID- 11309450
TI  - Excitatory and inhibitory corticospinal responses to transcranial magnetic
      stimulation in patients with minor to moderate head injury.
AB  - OBJECTIVES: The changes in excitatory and inhibitory responses to transcranial
      magnetic stimulation (TMS), as attested by motor evoked potential (MEP) and
      silent period (SP) parameters, were compared in patients who sustained minor to
      moderate head injury. METHODS: A total of 38 patients with brain concussion, and
      diffuse, focal, and combined brain injury and 20 healthy volunteers were
      examined. The MEPs and SPs were recorded from the abductor pollicis brevis muscle
      after single pulse TMS 2 weeks after head trauma. The parameters assessed were
      the MEP resting threshold, the MEP/M wave amplitude ratio, the central motor
      conduction time (CMCT), the SP threshold, the interthreshold difference (ITD),
      and the SP duration (SPD). RESULTS: The main finding was an increase in the ITD
      in patients with mild and moderate head injury due to the relatively greater
      augmentation of the MEP threshold. This was associated with a reduction of the
      MEP/M wave amplitude ratio. The degree of MEP and SP changes depended on severity
      of head injury and was not related to the type of brain lesions. The SPD did not
      differ significantly in brain concussion, or diffuse, focal and combined brain
      injury groups compared with the control group. The CMCT was prolonged in patients
      with diffuse and combined brain lesions. Among subjective complaints only fatigue
      was significantly related to ITD, MEP, and SP threshold abnormalities.
      CONCLUSIONS: The results suggest that mechanisms involved in MEP and SP
      generation are differently affected in head injury, the first being impaired more
      severely. The increase of the ITD accompanied by reduction of the MEP/M wave
      amplitude ratio may reflect a dissociated impairment of inhibitory and excitatory
      components of central motor control in head trauma.

PMID- 11309451
TI  - Dementia as a complication of schizophrenia.
AB  - OBJECTIVES: Cognitive impairment is known to occur in schizophrenia, and may be
      marked in institutionalised patients. The aim of this study was to determine
      whether it ever warrants an additional diagnosis of dementia. METHODS: A
      population of chronic schizophrenic patients who were aged 65 or younger and
      showed no organic risk factors for dementia were screened for presence of
      disorientation. Any showing this underwent neuropsychological testing, physical
      investigations, and structural and functional neuroimaging. Information about day
      to day cognitive function was also obtained from carers. RESULTS: Eight patients
      aged 28 to 64 were identified who showed disorientation; in all cases this was
      accompanied by general intellectual impairment and objective evidence of a
      dementia syndrome. The patients' schizophrenic symptoms were unexceptional and
      did not seem sufficient to account for their cognitive impairment.
      Neuropsychological testing disclosed relative sparing of visual and visuospatial
      function and language syntax, but pervasive deficits in memory and executive
      function. Brain CT demonstrated only minor abnormalities but most of the patients
      showed frontal or temporal hypoperfusion on SPECT. CONCLUSIONS: Dementia in
      schizophrenia seems to be a real entity with a neuropsychological signature
      similar to that of frontotemporal dementia. Functional but not structural imaging
      abnormalities may also be characteristic.

PMID- 11309453
TI  - Kinematic analysis of handwriting movements in patients with obsessive-compulsive
      disorder.
AB  - OBJECTIVES: Basal ganglia dysfunction is supposed to play a part in the
      pathophysiology of obsessive-compulsive disorder (OCD). A new computer aided
      technique for the analysis of hand movements, allowing the detection of subtle
      motor performance abnormalities, was applied in this study of patients with OCD
      and healthy controls. METHODS: Using a digitising graphic tablet, hand motor
      performance was studied in 22 unmedicated patients with OCD and compared with 22
      healthy controls. All subjects drew superimposed concentric circles with both the
      right and the left hand, in addition to writing a given sentence, their personal
      signature, and letter sequences in four different sizes. Kinematic parameters
      were calculated to quantify hand motion. RESULTS: Patients with OCD had
      significant impairments of handwriting performance, reflected by lower peak
      velocity (sentence t=3.6; p=0.001; signature t=2.8; p=0.01) and micrographia
      (sentence t=3.4; p=0.002; signature t=2.5; p=0.02), compared with controls and
      shortened acceleration phases per stroke (sentence t=2.4; p=0.02; signature
      t=4.1; p=0.000). By contrast, in repetitive drawing, patients with OCD had higher
      peak velocity than healthy controls (group x task interaction p<0.01). There were
      no significant differences in left and right hand performance between groups.
      Patients with early versus late age of onset differed in handwriting parameters,
      such as handwriting consistency. Greater severity of obsessions and compulsions
      correlated with increasingly poor handwriting performance in patients with OCD.
      CONCLUSIONS: A subtle motor dysfunction in OCD can be detected with a digitising
      tablet. The findings show handwriting impairments in patients with OCD, in line
      with the assumption that basal ganglia dysfunction is part of OCD
      pathophysiology. Repetitive motor pattern performance was not impaired, but
      rather tended to be even better in patients with OCD than in controls. The
      findings also support the concept that patients with OCD with early versus late
      age of onset differ in pathophysiological mechanisms and basal ganglia
      dysfunction.

PMID- 11309452
TI  - Affective-prosodic deficits in schizophrenia: comparison to patients with brain
      damage and relation to schizophrenic symptoms [corrected].
AB  - OBJECTIVE: Although affective prosody seems to be a dominant and lateralised
      communication function of the right hemisphere, focal lesions of either
      hemisphere may cause problems with its modulation. When impairment occurs after
      brain damage, the profiles of affective-prosodic disturbances differ depending on
      the hemisphere injured. Patients with left brain damage (LBD) improve their
      performance whereas patients with right brain damage (RBD) do not when the verbal
      articulatory demands of the test stimuli are reduced systematically. One of the
      major arguments for a right hemispheric contribution to schizophrenia has been
      the documentation of affective prosodic deficits under the assumption that these
      abnormalities reflect right hemispheric dysfunction. Thus, an essential question
      to resolve is whether the profile of affective prosodic disturbances in
      schizophrenia is similar to LBD or RBD, or represents a unique variation.
      METHODS: Data were collected from four subject groups: 45 chronic, medication
      stabilised, schizophrenic patients, 10 patients with focal LBD, nine patients
      with focal RBD, and 19 controls. All groups were tested on the aprosodia battery,
      which uses stimuli having incrementally reduced verbal-articulatory demands.
      Schizophrenic and aphasic symptoms were evaluated using standard assessment
      tools. RESULTS: For patients with impaired performance on the aprosodia battery,
      schizophrenic patients were statistically identical to patients with RBD and
      robustly different from those with LBD. Thirty eight schizophrenic patients
      (84.4%) were found to have some type of affective prosodic deficit with the
      predominant pattern indicating, at minimum, right posterior sylvian dysfunction
      (57.8%). When schizophrenic symptoms and aprosodic deficits were examined using a
      principal component analysis, affective comprehension and repetition loaded
      uniquely as separate factors. CONCLUSIONS: The profile of affective-prosodic
      deficits found in impaired schizophrenic patients is characteristic of RBD,
      supporting the concept that schizophrenia is a bihemispheric disease process.
      These deficits may also represent cardinal symptoms of schizophrenia as they are
      highly prevalent and, except for spontaneous affective prosody, are not
      associated statistically with traditional clusters of schizophrenic symptoms.

PMID- 11309454
TI  - Cluster headache in women: clinical characteristics and comparison with cluster
      headache in men.
AB  - OBJECTIVE: To study the clinical characteristics of cluster headache in women.
      Cluster headache is a disorder of men (male to female ratio 6-7:1). METHODS:
      Retrospective chart review to identify all women diagnosed with cluster headache
      at an academic headache centre from January 1995 through July 1998. RESULTS:
      Thirty two women and 69 men were identified. The mean age of onset of cluster
      headache was 29.4 years in women versus 31.3 years in men. Two peaks of onset in
      women (2nd and 5th decade) were identified compared with one in men (3rd decade).
      Episodic cluster headache was present in 75% of women and 77% of men. Women and
      men had on average 3 attacks a day, but attack duration was shorter in women
      (67.2 minutes v 88.2 minutes). Cluster headache period duration (11.1 weeks v 10
      weeks) and remission periods (21.1 months v 23.1 months) were similar in women
      and men. Miosis and ptosis seemed to be less common in women (miosis 13.3% v
      24.6%, ptosis 41.9% v 58.1%) whereas lacrimation and nasal congestion/rhinorrhoea
      were almost equally prevalent in women and men. Women had more nausea than men
      (62.5% v 43.5%, p=0.09) and significantly more vomiting (46.9% v 17.4%, p=0.003).
      Photophobia occurred in 75% of women and 81.2% of men, and phonophobia occurred
      in 50% of women and 47.8% of men. CONCLUSIONS: The clinical characteristics of
      cluster headache in women are very similar to those in men. Women develop the
      disorder at an earlier age of onset and experience more "migrainous symptoms"
      with cluster headache, especially vomiting. Both men and women have frequent
      photophobia and phonophobia with cluster headache attacks. These symptoms are not
      included in the International Headache Society cluster headache criteria,
      suggesting the need for possible criteria revision.

PMID- 11309455
TI  - Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a
      family with paralysis periodica paramyotonica.
AB  - OBJECTIVES: Patients with paralysis periodica paramyotonica exhibit a clinical
      syndrome with characteristics of both hyperkalaemic periodic paralysis and
      paramyotonia congenita. In several types of periodic paralysis associated with
      hyperkalaemia, mutations in the skeletal muscle sodium channel (SCN4A) gene have
      been previously reported. Phenotypic variations of mutations in SCN4A, however,
      have not been described yet. The present study aimed to evaluate genetic
      variations in a family with clinical and electrophysiological characteristics of
      paralysis periodica paramyotonia. METHODS: Seven members of a family affected
      with symptoms of paralysis periodica paramyotonia were studied by
      electrophysiological and genetic analyses. There were increased serum potassium
      concentrations in four members during paralytic attacks induced by hyperkalaemic
      periodic paralysis provocation tests. Short exercise tests before and after cold
      immersion were carried out in four patients to distinguish electrophysiological
      characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing
      analyses of SCN4A were performed on one patient and a normal control to identify
      polymorphisms. Restriction fragment length polymorphism (RFLP) analysis was then
      performed at the identified polymorphic sites. RESULTS: Electrophysiological
      studies showed both exercise sensitivity and temperature sensitivity. Compound
      motor action potential (CMAP) amplitudes were decreased (7.3%-28.6%) after short
      exercise tests. The CMAP amplitudes were even more severely decreased (21.7%
      56.5%) in short exercise tests after cold exposure. Three polymorphic sites,
      Gln371Glu, Thr704Met, and Aspl376Asn were identified in SCN4A. RFLP analyses
      showed that all affected patients carried the Thr704Met mutation, whereas
      unaffected family members and a normal control did not. CONCLUSION: Phenotypic
      variation of the Thr704Met mutation, which was previously reported in patients
      with hyperkalaemic periodic paralysis, is described in a family affected with
      paralysis periodica paramyotonia.

PMID- 11309456
TI  - Both total and phosphorylated tau are increased in Alzheimer's disease.
AB  - BACKGROUND: [corrected] Pathological tau protein concentrations in CSF are found
      in both Alzheimer's disease (AD) and frontotemporal dementia (FTD), but studies
      on brain tissue have suggested that the tau pathology in AD differs from that in
      FTD and that the difference may be related to the degree of phosphorylation. As
      CSF tau protein is increased after stroke, tau may also be implicated in the
      pathophysiology of vascular dementia, of which subcortical arteriosclerotic
      encephalopathy (SAE) is a putative subtype. OBJECTIVES: To investigate the nature
      of tau protein in CSF and the involvement of total CSF tau and phosphorylated CSF
      tau (phosphotau) in various types of dementia. METHODS: Using ELISAs for total
      tau and tau phosphorylated at Thr181 (phosphotau), the CSF concentrations of
      total tau and phosphotau were determined in patients with probable and possible
      AD (n=41 and 19, respectively), FTD (n=18), SAE (n=17), and Parkinson's disease
      (PD; n=15) and in age matched controls (n=17). All the antibodies stained the
      lower molecular weight bands, whereas only the antibodies that recognise
      phosphorylated tau stained the higher molecular bands. RESULTS: Both CSF tau and
      CSF phosphotau were increased in probable AD compared with FTD (p<0.001), SAE
      (p<0.001), PD (p<0.001), and controls (p<0.001). CSF phosphotau was increased in
      possible AD compared with FTD (p<0.001) and SAE (p<0.001). CSF tau and CSF
      phosphotau were positively correlated in all the groups. Molecular weight forms
      of tau ranging from 25 kDa to 80 kDa were found in the CSF CONCLUSION: Both
      phosphorylated and unphosphorylated tau isoforms were present in the CSF, and tau
      protein appeared in both truncated and full length forms. The results suggest
      that the CSF concentrations of tau and phosphotau are increased in about two
      thirds of patients with probable AD and in half of those with possible AD but are
      normal in FTD, SAE, and PD compared with normal aging. Values in the normal range
      do not exclude AD.

PMID- 11309457
TI  - The benefit of an acute stroke unit in patients with intracranial haemorrhage: a
      controlled trial.
AB  - OBJECTIVES: Patients with stroke receiving organised inpatient (stroke unit) care
      after stroke are more likely to be alive and independent compared with patients
      offered conventional care. The objective was to determine the effect of an acute
      stroke unit on patients with primary intracranial haemorrhage. METHODS: In a
      prospective controlled study, the effect of an acute stroke unit was examined on
      30 day and 1 year mortality in patients with primary intracranial haemorrhage.
      Patients treated in general medical wards served as controls. RESULTS: Of 121
      patients included, 56 were allocated to an acute stroke unit and 65 to a general
      medical ward. The 30 day mortality rate was 39% in the acute stroke unit compared
      with 63% in the general medical wards, and the 1 year mortality rates were 52%
      and 69%, respectively. There was a difference between the 30 day and 1 year
      survival curves between the groups (p=0.007 and 0.013, respectively); however,
      there was no difference in survival between 30 and 365 days. There was no
      difference in risks of being discharged home or to long term care between the
      groups. CONCLUSIONS: In this study admission to an acute stroke unit reduced
      mortality 30 days and 1 year after primary intracranial haemorrhage, which could
      be attributed to a large difference in survival during the first 30 days.

PMID- 11309458
TI  - Stance control is not affected by paresis and reflex hyperexcitability: the case
      of spastic patients.
AB  - OBJECTIVES: Spastic patients were studied to understand whether stance
      unsteadiness is associated with changes in the control of voluntary force, muscle
      tone, or reflex excitability, rather than to abnormal posture connected to the
      motor deficit itself. METHODS: Twenty four normal subjects, 12 patients affected
      by amyotrophic lateral sclerosis (ALS), seven by spastic paraparesis, and 14 by
      hemiparesis were studied. All patients featured various degrees of spasticity and
      paresis but were free from clinically evident sensory deficits. Body sway during
      quiet upright stance was assessed through a stabilometric platform under both
      eyes open (EO) and eyes closed (EC) conditions. The sudden rotation of a
      supporting platform, in a toe up and toe down direction respectively, evoked
      short (SLR) and medium latency (MLR) reflex responses to stretch of the soleus or
      the tibialis anterior (TA) muscle. RESULTS: No relation was found between
      clinical findings (tone, muscle strength, tendon reflexes, plantar response, and
      duration of disease) and body sway. On average, all patient groups exhibited a
      forward shift of the centre of foot pressure (CFP) with respect to normal
      subjects; in addition, paraparetic and to a much larger extent hemiparetic
      patients showed a lateral shift of CFP. Body sway area was significantly
      increased only in the hemiparetic patients. No relation was found between
      position of the CFP and sway within any patient group. Soleus SLR was increased
      in all patients with respect to normal subjects. TA SLR was often seen in both
      patients with ALS and paraparetic patients, but only rarely in normal subjects
      and hemiparetic patients. However, no relation was found between amplitude of
      soleus or TA SLRs and stabilometric variables. The frequency and size of soleus
      MLR and TA MLR were decreased in all patients. These responses were decreased in
      size and not modulated by background EMG in the affected leg of hemiparetic
      patients, suggesting a disturbed control of spinal reflexes fed by spindle group
      II afferent fibres. CONCLUSIONS: It is proposed that body posture, paresis, or
      monosynaptic reflex hyperexcitability do not affect the control of equilibrium
      during quiet upright stance. In hemiparetic patients, the decreased amplitude of
      MLRs might be the main cause of the large postural instability. The results are
      congruent with the hypothesis of a role for group II afferent input in the reflex
      control of equilibrium.

PMID- 11309459
TI  - Reconsideration of biallelic inactivation of the VHL tumour suppressor gene in
      hemangioblastomas of the central nervous system.
AB  - OBJECTIVES: Cerebellar haemangioblastoma occurs sporadically or as a component
      tumour of autosomal dominant von Hippel-Lindau disease. Biallelic inactivation of
      the VHL tumour suppressor gene, which is located on chromosome 3p, has been shown
      to be involved in the pathogenesis of both tumour entities. Mechanisms of VHL
      inactivation are intragenic mutations, mitotic recombination events, and
      hypermethylation of the promoter region. The systematic and complete examination
      of these genetic and epigenetic phenomena in large series of von Hippel-Lindau
      disease related and sporadic hemangioblastomas has, thus far, not been performed.
      METHODS: In the largest series to date, 29 von Hippel-Lindau disease associated
      and 13 sporadic haemangioblastomas were investigated for all suggested
      inactivating mechanisms of the VHL gene using single strand conformational
      polymorphism (SSCP), loss of heterozygosity (LOH), and methylation analyses.
      Additionally, corresponding blood samples of all patients were screened for VHL
      germline mutations by SSCP and Southern blotting. RESULTS: Germline mutations
      were identified in 94% of patients with von Hippel-Lindau disease and their
      tumours and 62% of these hemangioblastomas showed LOH of chromosome 3p. Of the 13
      sporadic tumours, 23% showed a single somatic mutation of the VHL gene that was
      not present in the germline. 3p LOH was identified in 50% of informative sporadic
      tumours. No von Hippel-Lindau disease related or sporadic tumour demonstrated VHL
      promoter hypermethylation. CONCLUSIONS: For most von Hippel-Lindau disease
      related haemangioblastomas, the inactivation or loss of both alleles of the VHL
      gene, as predicted by the Knudson two hit theory, is required. However, in a
      subset of tumours including most sporadic haemangioblastomas, the genetic
      pathways involved in tumorigenesis have yet to be defined and may represent
      alterations of a different pathway or pathways.

PMID- 11309460
TI  - The "burden of normality": concepts of adjustment after surgery for seizures.
AB  - OBJECTIVES: To conceptualise the process of adjustment provoked by the sudden
      alleviation of chronic epilepsy by temporal lobectomy. On being rendered seizure
      free, the process of adjustment primarily depends on the patient's capacity to
      discard roles associated with chronic epilepsy and to learn to become well. This
      can involve a reconceptualisation of the patient's identity from chronically ill
      to "cured", and can give rise to a constellation of psychological, affective,
      behavioural, and sociological features characterised as the "burden of
      normality". METHODS: This is a theoretical inquiry that documents the clinical
      phenomenology of the burden of normality by classifying its key psychological and
      psychosocial features. The model of adjustment is presented in the context of
      previous outcome research on surgery for seizures, providing a conceptual link
      between practice based rehabilitation measures of outcome and multidimensional
      constructs, such as health related quality of life. RESULTS: The model represents
      a process oriented, theoretical framework for comprehensively measuring outcome
      after life changing medical interventions. It has implications for clinical
      practice, including the identification of preoperative predictors of outcome and
      informing appropriate management and rehabilitation of patients. CONCLUSION: This
      model of outcome after temporal lobectomy may ultimately be applicable to the
      treatment of other chronic conditions.

PMID- 11309461
TI  - Benzodiazepine receptor quantification in Huntington's disease with
      [(123)I]omazenil and SPECT.
AB  - OBJECTIVES: Increasing evidence suggests that metabolic changes predate neuronal
      death in Huntington's disease and emission tomography methods (PET and SPECT)
      have shown changes in glucose consumption and receptor function in early and
      possibly even presymptomatic disease. Because the GABA(A)-benzodiazepine receptor
      complex (BZR) is expressed on virtually all cerebral neurons BZR density images
      may be used to detect neuronal death. In this study the regional cerebral
      [(123)I]iomazenil binding to BZR was determined in patients with Huntington's
      disease and normal controls by a steady state method and SPECT. METHODS: Seven
      patients mildly to moderately affected by Huntington's disease and seven age
      matched controls were studied. Brain CT was performed on all subjects. In each
      subject two [(123)I]iomazenil-SPECT measurements were acquired-one with and one
      without infusion of flumazenil. The affinity constant of flumazenil (Kd) was
      calculated from the paired distribution volumes (DV) and the free plasma
      flumazenil concentration. The distribution volume of [(123)I]iomazenil in the
      unblocked condition (DV(0)) reflects the ratio between BZR density and Kd.
      RESULTS: Flumazenil Kd was similar in the Huntington's disease group and the
      control group (11.3 v 11.2 mM). For the Huntington's disease group a 31%
      reduction in striatal DV(0) (p=0.03) was found. In the cortical regions, DV(0)
      was similar in patients and in controls. In Huntington's disease, DV(0)
      correlated significantly with functional capacity (p=0.04) and chorea symptoms
      (p=0.02). The clinically least affected patients displayed DV(0)s within the
      range of those of the control group (19-35 ml/ml). CONCLUSIONS: The finding of an
      unchanged Kd of flumazenil in patients indicates that the BZR is functionally
      intact in Huntington's disease. That is, the reduction in DV(0) for BZR
      represents a selective decrease in the number of striatal BZRs. DV(0)
      significantly correlated with functional loss and [(123)I]iomazenil-SPECT could
      be an important tool for validation of the effect of future therapeutic
      strategies aimed at limiting oxidative stress and free radicals in Huntington's
      disease.

PMID- 11309462
TI  - Clinical phenotype in patients with alpha-synuclein Parkinson's disease living in
      Greece in comparison with patients with sporadic Parkinson's disease.
AB  - OBJECTIVE: An Ala53Thr mutation of the alpha-synuclein gene has been recently
      identified as a rare cause of autosomal Parkinson's disease (PD). The clinical
      characteristics of 15 patients with PD living in Greece with the Ala53Thr alpha
      synuclein mutation (alpha-synPD) were compared with patients with sporadic
      Parkinson's disease (sPD). METHODS: An investigator, blind to the results of the
      genetic analysis, examined 15 patients with alpha-synPD and 52 consecutive
      patients with sPD. Demographic data, age at onset of the illness, modality of
      presentation, and duration of PD were collected. The unified Parkinson's disease
      rating scale, the Hoehn and Yahr scale, and the Schwab-England scale were
      completed. The patients with alpha-synPD were matched for duration of disease
      with 32 of the 52 patients with sporadic PD (MsPD group). RESULTS: Patients with
      the alpha-synuclein mutation were significantly younger (mean 7.6 years), showed
      the first sign of the disease significantly earlier in life (mean 10.8 years),
      and had significantly longer duration of the disease compared with patients with
      sPD. Tremor at onset of the disease was present in only one (6.7%) of the
      patients with alpha-synPD, whereas it was present in 32 (61.5%) of the patients
      with sPD (p=0.0006). During the course of the disease one patient in the alpha
      synPD group went on to develop tremor compared with six patients in the sPD
      group. Rigidity, bradykinesia, postural instability, orthostatic hypotension,
      intellectual impairment, depression, complications of therapy, and clinical
      severity of the disease at the time of examination did not differ significantly
      between patients with alpha-synPD and those with sPD, or between patients with
      alpha-synPD and the MsPD group. CONCLUSION: The younger age at onset of the
      illness, the much lower prevalence of tremor, and the longer duration of the
      disease characterise the clinical phenotype in this sample of patients with alpha
      synPD. The other symptoms and signs of the illness did not seem to differentiate
      the patients with alpha-synPD from those with sPD.

PMID- 11309464
TI  - Massive haemorrhagic transformation in cardioembolic stroke: the role of arterial
      wall trauma and dissection.
AB  - The pathogenesis of massive haemorrhagic transformation is not well established.
      Fatal haemorrhagic transformation associated with in situ dissection after acute
      middle cerebral artery (MCA) occlusion in a patient with atrial fibrillation is
      reported. An 80 year old woman with atrial fibrillation developed mild
      hemiparesis and aphasia. Brain CT and MRI at 4 and 5 hours, respectively, of
      symptom onset showed proximal MCA trunk occlusion with developing striatocapsular
      infarct and hypoperfusion in the superficial MCA territory. A few hours later,
      she developed massive bleeding into the ischaemic area and died. Pathological
      examination showed MCA trunk dissection, surrounded by a subarachnoid clot which
      communicated with the cerebral haematoma. It is suggested that direct arterial
      wall trauma as a result of cardioembolic MCA occlusion caused bleeding into the
      infarct. Secondary in situ dissection may be an overlooked mechanism of
      haemorrhagic transformation.

PMID- 11309463
TI  - Immediate and long term outcome after infrathalamic and thalamic lesioning for
      intractable Tourette's syndrome.
AB  - OBJECTIVE: The surgical treatment of intractable Tourette's syndrome is
      controversial. Experience with 17 consecutive patients treated between 1970 and
      1998 is reviewed and the efficacy and safety of surgical treatment is assessed.
      METHODS: These patients were retrospectively reclassified into subtypes according
      to the protocol of the Tourette's Syndrome Study Group. One patient was excluded
      from the study. Ventriculography based stereotactic zona incerta (ZI) and
      ventrolateral/ lamella medialis thalamotomy (VL/LM) were performed on all
      patients. The preoperative, postoperative, and late tic severities were assessed
      by the tic severity rating scale. The median follow up of 11 patients (65%) was 7
      years (range 3.5-17 years) and six patients were lost to long term follow up.
      RESULTS: Median age was 23 years (range 11-40) at the time of surgery. Median
      duration of illness was 14 years (range 3-33). The mean preoperative motor and
      vocal tic severities were estimated to be 4.44 (SD 0.63) and 3.81 (SD 0.66),
      respectively. Unilateral ZI lesioning and VL/LM lesioning selected by asymmetry
      of symptoms provide an effective control of tic severity (p motor and
      vocal<0.001). In attenuation of contralateral symptoms, a second surgical
      intervention in the relevant side could reduce tic severity sufficiently (p
      motor<0.01; p vocal<0.005). Transient complications occurred in 68% of patients.
      Only one permanent complication was registered in six patients followed up after
      unilateral surgery. Two out of five patients followed up after bilateral surgery
      had disabling side effects of surgery. CONCLUSIONS: ZI and VL/LM lesioning
      provide a significant long term reduction of tic severity in intractable
      Tourette's syndrome. Adequate selection of the side of first intervention might
      prevent the patient from increased risk of bilateral surgery.

PMID- 11309465
TI  - Reversible brain dysfunction in MELAS: MEG, and (1)H MRS analysis.
AB  - This case report describes a follow up investigation of a patient with impaired
      word discrimination due to mitochondrial encephalopathy with lactic acidosis and
      stroke-like syndrome (MELAS) using proton magnetic resonance spectroscopy ((1)H
      MRS) and auditory evoked magnetic fields (AEFs). The initial (1)H MRS showed no N
      acetyl aspartate (NAA) and marked accumulation of lactate (Lac) in the stroke
      like lesion of MELAS, which was silent in neural activity according to AEFs. The
      follow up investigations, however, demonstrated that NAA reappeared, that the
      formerly increased Lac signal was significantly reduced, and that the magnitude
      of AEFs of the lesion was markedly increased. Metabolic and functional changes in
      (1)H MRS and AEFs reflected the neurological recovery very well. The stroke-like
      lesion was shown, using AEFs and (1)H MRS, to be able to function properly,
      although brain tissue of the lesion initially had severe damage due to
      mitochondrial dysfunction.

PMID- 11309466
TI  - Neurological stamp: Paul Ehrlich (1854-1915) and Emil Adolf von Behring (1854
      1917).

PMID- 11309467
TI  - Effect of experience of severe stroke on subjective valuations of quality of life
      after stroke.
AB  - Previous work suggests that the quality of life associated with severe disability
      after stroke is rated very poorly by members of the public, often as being worse
      than death. Other evidence suggests that experience of illness alters perceptions
      of its severity. This was tested for severe stroke. Eleven patients with severely
      disabling stroke, but able to complete a standard gamble interview, 22 age and
      sex matched controls, and 20 health professionals participated. A standard gamble
      interview was carried out to determine the quality of life (utility) associated
      with three hypothetical scenarios representing mild, moderate, and severe stroke,
      and current health. A sample was retested for reliability, and comparisons were
      made with other measures of health status. All three subject groups showed wide
      variation in the utilities they attached to each of the scenarios. The control
      subjects' valuations were lower than those of either patients or staff members,
      especially for moderate stroke (median 0.30, 0.73, and 0.68 respectively). There
      were weak to moderate correlations between utilities and other measures of health
      status including the Barthel index (r=0.51) and Rivermead mobility score
      (r=0.24). Test retest-reliability was modest (reliability coefficient 0.75), but
      indicators of the internal validity of the results were good. In conclusion, it
      cannot be assumed that general population valuations are valid for patient
      groups. In clinical practice it is unsafe to make any assumption about subjective
      quality of life after stroke, due to the wide range of valuations given, although
      many people rate severe and moderate stroke at least as bad as death.

PMID- 11309468
TI  - Cerebral aneurysms associated with Behcet's disease: a case report.
AB  - Cerebral aneurysms in Behcet's disease are very rare. The role of vasculitis in
      the aetiology of these aneurysms has not been clarified. A 57 year old man with
      Behcet's disease is described, who had a subarachnoid hemorrhage due to rupture
      of a peripheral middle cerebral artery aneurysm. He underwent a successful
      aneurysmal clipping. Three years later he had seizures and was found to have a
      new aneurysm on the contralateral peripheral middle cerebral artery as well as
      some radiological features of vasculitis. After 3 months of steroid therapy, the
      aneurysm disappeared. Although surgical treatment is the first choice for
      ruptured aneurysms, steroid therapy may be effective for unruptured small
      aneurysms in patients with Behcet's disease.

PMID- 11309469
TI  - Axonal polyneuropathy in obstructive sleep apnoea.
AB  - Chronic hypoxaemia in chronic obstructive pulmonary disease is a well known risk
      factor for polyneuropathy but the impact of intermittent hypoxaemia on peripheral
      nerve function has not been established so far. A case-control study was
      performed to evaluate the prevalence of polyneuropathy in obstructive sleep
      apnoea (OSA). Out of 24 patients with OSA, 17 (71%) had clinical signs of
      polyneuropathy versus seven (33%) out of 21 matched controls. The mean amplitude
      of the sural sensory nerve action potential was smaller in the OSA group than in
      the control group, indicating axonal nerve damage. The differences were
      significant and could not be attributed to other known risk factors for
      polyneuropathy. The severity of axonal damage in patients with OSA correlated
      with the percentage of the night time with an O(2) saturation below 90%. It is
      assumed that recurrent intermittent hypoxaemia in OSA is an independent risk
      factor for axonal damage of peripheral nerves.

PMID- 11309470
TI  - Ocular contrapulsion in multiple sclerosis: clinical features and
      pathophysiological mechanisms.
AB  - The objective was to describe in multiple sclerosis, a cerebellar eye movement
      syndrome that resulted from an acute episode of inflammatory demyelination.
      Contrapulsion is an ocular motor disturbance characterised by a triad of (1)
      hypermetric saccadic eye movements in a direction opposite from a precisely
      localised lesion within a specific white matter pathway, the uncinate fasciculus,
      at the level of the superior cerebellar peduncle (SCP); (2) hypometric saccades
      towards the side of the lesion; (3) oblique saccades directed away from the side
      of the lesion on attempted vertical saccades. Infrared oculography was used to
      demonstrate the characteristic features of contrapulsion in two patients with
      multiple sclerosis. Brain MRI showed lesions within the region of the uncinate
      fasciculus and superior cerebellar peduncle in both patients. Eye movement
      recordings showed saccadic hypermetria away from the side of the lesion and
      saccadic hypometria towards the side of the lesion. The hypometria decomposed
      into a series of stepwise movements as the eye approached the target. Oblique
      saccades directed away from the side of the lesion were seen on attempted
      vertical saccades. In conclusion, ocular contrapulsion can be seen in patients
      with multiple sclerosis and results from a lesion in the region of the SCP,
      involving the uncinate fasciculus.

PMID- 11309471
TI  - Comparative study of preceding Campylobacter jejuni infection in Guillain-Barre
      syndrome in Japan and The Netherlands.
AB  - A comparative study was made in Japan and The Netherlands of the presence of
      preceding Campylobacter jejuni infections in Guillain-Barre syndrome (GBS). It
      was conducted in two laboratories using different serological criteria. The
      Japanese results showed no significant difference in the frequency of C jejuni
      infection between the Japanese (17/88, 19%) and Dutch (21/132, 16%) patients with
      GBS. The Dutch investigation showed a higher frequency in Dutch patients (45/132;
      34%) than in Japanese patients(20/88; 23%), but the difference did not reach
      significance. Although the frequencies of preceding C jejuni infection have been
      reported to be higher in Asian countries than in western countries, the findings
      of this collaborative study show that the incidence of antecedent C jejuni
      infection in GBS in Japan is not higher than in The Netherlands and that
      serological assays vary considerably between laboratories.

PMID- 11309472
TI  - Atypical form of dural graft associated Creutzfeldt-Jakob disease: report of a
      postmortem case with review of the literature.
AB  - A postmortem case of an atypical form of dural graft associated Creutzfeldt-Jakob
      disease (CJD) is described. A 42 year old man developed progressive spastic
      paresis 163 months after a cadaveric dura mater graft. He presented with no
      myoclonus and very late occurrence of periodic synchronous discharges on EEG. The
      prion protein (PrP) gene was homozygous for methionine at the polymorphic codon
      129. Neuropathological examination disclosed plaque-like PrP deposits with
      atypical distribution of synaptic PrP accumulations in the brain. This patient
      represents an atypical form of dural graft associated CJD characterised by
      unusual clinicopathological features.

PMID- 11309473
TI  - Aphasia and Wernicke's arc.

PMID- 11309474
TI  - Intravenous hypertrophic Paccioni granulations: differentiation from venous dural
      thrombosis.

PMID- 11309480
TI  - The binding conformation of Taxol in beta-tubulin: a model based on electron
      crystallographic density.
AB  - The chemotherapeutic drug Taxol is known to interact within a specific site on
      beta-tubulin. Although the general location of the site has been defined by
      photoaffinity labeling and electron crystallography, the original data were
      insufficient to make an absolute determination of the bound conformation. We have
      now correlated the crystallographic density with analysis of Taxol conformations
      and have found the unique solution to be a T-shaped Taxol structure. This T
      shaped or butterfly structure is optimized within the beta-tubulin site and
      exhibits functional similarity to a portion of the B9-B10 loop in the alpha
      tubulin subunit. The model provides structural rationalization for a sizeable
      body of Taxol structure-activity relationship data, including binding affinity,
      photoaffinity labeling, and acquired mutation in human cancer cells.

PMID- 11309481
TI  - Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine
      phosphatase in muscle causes insulin resistance.
AB  - Previous reports indicate that the expression and/or activity of the protein
      tyrosine phosphatase (PTP) LAR are increased in insulin-responsive tissues of
      obese, insulin-resistant humans and rodents, but it is not known whether these
      alterations contribute to the pathogenesis of insulin resistance. To address this
      question, we generated transgenic mice that overexpress human LAR, specifically
      in muscle, to levels comparable to those reported in insulin-resistant humans. In
      LAR-transgenic mice, fasting plasma insulin was increased 2.5-fold compared with
      wild-type controls, whereas fasting glucose was normal. Whole-body glucose
      disposal and glucose uptake into muscle in vivo were reduced by 39-50%. Insulin
      injection resulted in normal tyrosyl phosphorylation of the insulin receptor and
      insulin receptor substrate 1 (IRS-1) in muscle of transgenic mice. However,
      phosphorylation of IRS-2 was reduced by 62%, PI3' kinase activity associated with
      phosphotyrosine, IRS-1, or IRS-2 was reduced by 34-57%, and association of
      p85alpha with both IRS proteins was reduced by 39-52%. Thus, overexpression of
      LAR in muscle causes whole-body insulin resistance, most likely due to
      dephosphorylation of specific regulatory phosphotyrosines on IRS proteins. Our
      data suggest that increased expression and/or activity of LAR or related PTPs in
      insulin target tissues of obese humans may contribute to the pathogenesis of
      insulin resistance.

PMID- 11309483
TI  - Estimating risks in declining populations with poor data.
AB  - Census data on endangered species are often sparse, error-ridden, and confined to
      only a segment of the population. Estimating trends and extinction risks using
      this type of data presents numerous difficulties. In particular, the estimate of
      the variation in year-to-year transitions in population size (the "process error"
      caused by stochasticity in survivorship and fecundities) is confounded by the
      addition of high sampling error variation. In addition, the year-to-year
      variability in the segment of the population that is sampled may be quite
      different from the population variability that one is trying to estimate. The
      combined effect of severe sampling error and age- or stage-specific counts leads
      to severe biases in estimates of population-level parameters. I present an
      estimation method that circumvents the problem of age- or stage-specific counts
      and is markedly robust to severe sampling error. This method allows the
      estimation of environmental variation and population trends for extinction-risk
      analyses using corrupted census counts--a common type of data for endangered
      species that has hitherto been relatively unusable for these analyses.

PMID- 11309482
TI  - Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4
      homozygosity.
AB  - Certain HLA-B antigens have been associated with lack of progression to AIDS. HLA
      B alleles can be divided into two mutually exclusive groups based on the
      expression of the molecular epitopes HLA-Bw4 and HLA-Bw6. Notably, in addition to
      its role in presenting viral peptides for immune recognition, the HLA-Bw4, but
      not HLA-Bw6, motif functions as a ligand for a natural killer cell inhibitory
      receptor (KIR). Here, we show that profound suppression of HIV-1 viremia is
      significantly associated with homozygosity for HLA-B alleles that share the HLA
      Bw4 epitope. Furthermore, homozygosity for HLA-Bw4 alleles was also significantly
      associated with the ability to remain AIDS free and to maintain a normal CD4 T
      cell count in a second cohort of HIV-1-infected individuals with well defined
      dates of seroconversion. This association was independent of the presence of a
      mutation in CC chemokine receptor 5 (CCR5) associated with resistance to HIV-1
      infection, and it was independent of the presence of HLA alleles that could
      potentially confound the results. We conclude that homozygosity for HLA-Bw4
      bearing B alleles is associated with a significant advantage and that the HLA-Bw4
      motif is important in AIDS pathogenesis.

PMID- 11309484
TI  - Influences of aging and caloric restriction on the transcriptional profile of
      skeletal muscle from rhesus monkeys.
AB  - In laboratory rodents, caloric restriction (CR) retards several age-dependent
      physiological and biochemical changes in skeletal muscle, including increased
      steady-state levels of oxidative damage to lipids, DNA, and proteins. We have
      previously used high-density oligonucleotide arrays to show that CR can prevent
      or delay most of the major age-related transcriptional alterations in the
      gastrocnemius muscle of C57BL/6 mice. Here we report the effects of aging and
      adult-onset CR on the gene expression profile of 7,070 genes in the vastus
      lateralis muscle from rhesus monkeys. Gene expression analysis of aged rhesus
      monkeys (mean age of 26 years) was compared with that of young animals (mean age
      of 8 years). Aging resulted in a selective up-regulation of transcripts involved
      in inflammation and oxidative stress, and a down-regulation of genes involved in
      mitochondrial electron transport and oxidative phosphorylation. Middle-aged
      monkeys (mean age of 20 years) subjected to CR since early adulthood (mean age of
      11 years) were studied to determine the gene expression profile induced by CR. CR
      resulted in an up-regulation of cytoskeletal protein-encoding genes, and also a
      decrease in the expression of genes involved in mitochondrial bioenergetics.
      Surprisingly, we did not observe any evidence for an inhibitory effect of adult
      onset CR on age-related changes in gene expression. These results indicate that
      the induction of an oxidative stress-induced transcriptional response may be a
      common feature of aging in skeletal muscle of rodents and primates, but the
      extent to which CR modifies these responses may be species-specific.

PMID- 11309485
TI  - Covert attention accelerates the rate of visual information processing.
AB  - Whenever we open our eyes, we are confronted with an overwhelming amount of
      visual information. Covert attention allows us to select visual information at a
      cued location, without eye movements, and to grant such information priority in
      processing. Covert attention can be voluntarily allocated, to a given location
      according to goals, or involuntarily allocated, in a reflexive manner, to a cue
      that appears suddenly in the visual field. Covert attention improves
      discriminability in a wide variety of visual tasks. An important unresolved issue
      is whether covert attention can also speed the rate at which information is
      processed. To address this issue, it is necessary to obtain conjoint measures of
      the effects of covert attention on discriminability and rate of information
      processing. We used the response-signal speed-accuracy tradeoff (SAT) procedure
      to derive measures of how cueing a target location affects speed and accuracy in
      a visual search task. Here, we show that covert attention not only improves
      discriminability but also accelerates the rate of information processing.

PMID- 11309486
TI  - Characterization of a Plasmodium falciparum erythrocyte-binding protein
      paralogous to EBA-175.
AB  - A member of a Plasmodium receptor family for erythrocyte invasion was identified
      on chromosome 13 from the Plasmodium falciparum genome sequence of the Sanger
      Centre (Cambridge, U.K.). The protein (named BAEBL) has homology to EBA-175, a P.
      falciparum receptor that binds specifically to sialic acid and the peptide
      backbone of glycophorin A on erythrocytes. Both EBA-175 and BAEBL localize to the
      micronemes, organelles at the invasive ends of the parasites that contain other
      members of the family. Like EBA-175, the erythrocyte receptor for BAEBL is
      destroyed by neuraminidase and trypsin, indicating that the erythrocyte receptor
      is a sialoglycoprotein. Its specificity, however, differs from that of EBA-175 in
      that BAEBL can bind to erythrocytes that lack glycophorin A, the receptor for EBA
      175. It has reduced binding to erythrocytes with the Gerbich mutation found in
      another erythrocyte, sialoglycoprotein (glycophorin C/D). The interest in BAEBL's
      reduced binding to Gerbich erythrocytes derives from the high frequency of the
      Gerbich phenotype in some regions of Papua New Guinea where P. falciparum is
      hyperendemic.

PMID- 11309487
TI  - Factors regulating template switch in vitro by viral RNA-dependent RNA
      polymerases: implications for RNA-RNA recombination.
AB  - Copy-choice RNA recombination occurs during viral RNA synthesis when the viral
      transcription complex switches templates. We demonstrate that RNA-dependent RNA
      polymerase from bovine viral diarrhea virus and the replicases from three plant
      infecting RNA viruses can produce easily detectable recombination products in
      vitro by switching templates during elongative RNA synthesis. Template sequence
      and/or structure, and NTP availability affected the frequency of template switch
      by the transcription complex. Our results provide biochemical support for copy
      choice recombination and establish assays for mechanistic analyses of
      intermolecular RNA recombination in vitro.

PMID- 11309488
TI  - Early Pleistocene 40Ar/39Ar ages for Bapang Formation hominins, Central Jawa,
      Indonesia.
AB  - The Sangiran dome is the primary stratigraphic window for the Plio-Pleistocene
      deposits of the Solo basin of Central Jawa. The dome has yielded nearly 80 Homo
      erectus fossils, around 50 of which have known findspots. With a hornblende
      (40)Ar/(39)Ar plateau age of 1.66 +/- 0.04 mega-annum (Ma) reportedly associated
      with two fossils [Swisher, C.C., III, Curtis, G. H., Jacob, T., Getty, A. G.,
      Suprijo, A. & Widiasmoro (1994) Science 263, 1118-1121), the dome offers evidence
      that early Homo dispersed to East Asia during the earliest Pleistocene.
      Unfortunately, the hornblende pumice was sampled at Jokotingkir Hill, a central
      locality with complex lithostratigraphic deformation and dubious specimen
      provenance. To address the antiquity of Sangiran H. erectus more systematically,
      we investigate the sedimentary framework and hornblende (40)Ar/(39)Ar age for
      volcanic deposits in the southeast quadrant of the dome. In this sector, Bapang
      (Kabuh) sediments have their largest exposure, least deformation, and most
      complete tephrostratigraphy. At five locations, we identify a sequence of
      sedimentary cycles in which H. erectus fossils are associated with epiclastic
      pumice. From sampled pumice, eight hornblende separates produced (40)Ar/(39)Ar
      plateau ages ranging from 1.51 +/- 0.08 Ma at the Bapang/Sangiran Formation
      contact, to 1.02 +/- 0.06 Ma, at a point above the hominin-bearing sequence. The
      chronological sequence of (40)Ar/(39)Ar ages follows stratigraphic order across
      the southeast quadrant. An intermediate level yielding four nearly complete
      crania has an age of about 1.25 Ma.

PMID- 11309489
TI  - Hydrophobic moments of protein structures: spatially profiling the distribution.
AB  - It is generally accepted that globular proteins fold with a hydrophobic core and
      a hydrophilic exterior. Might the spatial distribution of amino acid
      hydrophobicity exhibit common features? The hydrophobic profile detailing this
      distribution from the protein interior to exterior has been examined for 30
      relatively diverse structures obtained from the Protein Data Bank, for 3 proteins
      of the 30S ribosomal subunit, and for a simple set of 14 decoys. A second-order
      hydrophobic moment has provided a simple measure of the spatial variation. Shapes
      of the calculated spatial profiles of all native structures have been found to be
      comparable. Consequently, profile shapes as well as particular profile features
      should assist in validating predicted protein structures and in discriminating
      between different protein-folding pathways. The spatial profiles of the 14 decoys
      are clearly distinguished from the profiles of their native structures.

PMID- 11309490
TI  - Erythropoietin induces tumor regression and antitumor immune responses in murine
      myeloma models.
AB  - Recombinant human erythropoietin (rHuEpo) has been used successfully in the
      treatment of cancer-related anemia. Clinical observations with several patients
      with multiple-myeloma treated with rHuEpo has shown, in addition to the improved
      quality of life, a longer survival than expected, considering the poor prognostic
      features of these patients. Based on these observations, we evaluated the
      potential biological effects of rHuEpo on the course of tumor progression by
      using murine myeloma models (MOPC-315-IgAlambda(2) and 5T33 MM-IgG(2b)). Here we
      report that daily treatment of MOPC-315 tumor-bearing mice with rHuEpo for
      several weeks induced complete tumor regression in 30-60% of mice. All regressors
      that were rechallenged with tumor cells rejected tumor growth, and this
      resistance was tumor specific. The Epo-triggered therapeutic effect was shown to
      be attributed to a T cell-mediated mechanism. Serum Ig analysis indicated a
      reduction in MOPC-315 lambda light chain in regressor mice. Intradermal
      inoculation of 5T33 MM tumor cells followed by Epo treatment induced tumor
      regression in 60% of mice. The common clinical manifestation of myeloma bone
      disease in patients with multiple-myeloma was established in these myeloma
      models. Epo administration to these tumor-bearing mice markedly prolonged their
      survival and reduced mortality. Therefore, erythropoietin seems to act as an
      antitumor therapeutic agent in addition to its red blood cell-stimulating
      activity.

PMID- 11309491
TI  - Skp2 is oncogenic and overexpressed in human cancers.
AB  - Skp2 is a member of the F-box family of substrate-recognition subunits of SCF
      ubiquitin-protein ligase complexes that has been implicated in the ubiquitin
      mediated degradation of several key regulators of mammalian G(1) progression,
      including the cyclin-dependent kinase inhibitor p27, a dosage-dependent tumor
      suppressor protein. In this study, we examined Skp2 and p27 protein expression by
      immunohistochemistry in normal oral epithelium and in different stages of
      malignant oral cancer progression, including dysplasia and oral squamous cell
      carcinoma. We found that increased levels of Skp2 protein are associated with
      reduced p27 in a subset of oral epithelial dysplasias and carcinomas compared
      with normal epithelial controls. Tumors with high Skp2 (>20% positive cells)
      expression invariably showed reduced or absent p27 and tumors with high p27 (>20%
      positive cells) expression rarely showed Skp2 positivity. Increased Skp2 protein
      levels were not always correlated with increased cell proliferation (assayed by
      Ki-67 staining), suggesting that alterations of Skp2 may contribute to the
      malignant phenotype without affecting proliferation. Skp2 protein overexpression
      may lead to accelerated p27 proteolysis and contribute to malignant progression
      from dysplasia to oral epithelial carcinoma. Moreover, we also demonstrate that
      Skp2 has oncogenic potential by showing that Skp2 cooperates with H-Ras(G12V) to
      malignantly transform primary rodent fibroblasts as scored by colony formation in
      soft agar and tumor formation in nude mice. The observations that Skp2 can
      mediate transformation and is up-regulated during oral epithelial carcinogenesis
      support a role for Skp2 as a protooncogene in human tumors.

PMID- 11309492
TI  - Thymocyte-targeted overexpression of xiap transgene disrupts T lymphoid apoptosis
      and maturation.
AB  - The X-linked inhibitor of apoptosis (XIAP) and other members of the inhibitor of
      apoptosis (IAP) family can suppress apoptosis induced by a diverse variety of
      triggers. Functional studies done to date have focused on tissue culture models
      and adenovirus overexpression of XIAP and other IAP proteins. Here we report the
      phenotype of an engineered transgenic mouse overexpressing a human IAP, as well
      as assessing the long-term consequence of IAP overexpression. We document the
      relative protein expression levels of the endogenous mouse homologue to XIAP,
      mouse inhibitor of apoptosis (MIAP 3), within thymocyte and T cell
      subpopulations. The consequence of lymphoid-targeted overexpression of XIAP in
      transgenic mice suggests a physiological role for the endogenous protein, MIAP3.
      Xiap-transgenic mice accumulated thymocytes and/or T cells in primary and
      secondary lymphoid tissue, T cell maturation was perturbed, and transgenic
      thymocytes resisted a variety of apoptotic triggers both in vitro and in vivo.
      These observations imply a possible key function for the intrinsic cellular
      inhibitor XIAP in maintaining the homeostasis of the immune system.

PMID- 11309493
TI  - Structure-based design of selective and potent G quadruplex-mediated telomerase
      inhibitors.
AB  - The telomerase enzyme is a potential therapeutic target in many human cancers. A
      series of potent inhibitors has been designed by computer modeling, which exploit
      the unique structural features of quadruplex DNA. These 3,6,9-trisubstituted
      acridine inhibitors are predicted to interact selectively with the human DNA
      quadruplex structure, as a means of specifically inhibiting the action of human
      telomerase in extending the length of single-stranded telomeric DNA. The anilino
      substituent at the 9-position of the acridine chromophore is predicted to lie in
      a third groove of the quadruplex. Calculated relative binding energies predict
      enhanced selectivity compared with earlier 3,6-disubstituted compounds, as a
      result of this substituent. The ranking order of energies is in accord with
      equilibrium binding constants for quadruplex measured by surface plasmon
      resonance techniques, which also show reduced duplex binding compared with the
      disubstituted compounds. The 3,6,9-trisubstututed acridines have potent in vitro
      inhibitory activity against human telomerase, with EC(50) values of up to 60 nM.

PMID- 11309494
TI  - Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the
      alpha -secretase ADAM 10.
AB  - Biochemical, epidemiological, and genetic findings demonstrate a link between
      cholesterol levels, processing of the amyloid precursor protein (APP), and
      Alzheimer's disease. In the present report, we identify the alpha-secretase ADAM
      10 (a disintegrin and metalloprotease) as a major target of the cholesterol
      effects on APP metabolism. Treatment of various peripheral and neural cell lines
      with either the cholesterol-extracting agent methyl-beta-cyclodextrin or the
      hydroxymethyl glutaryl-CoA reductase inhibitor lovastatin resulted in a drastic
      increase of secreted alpha-secretase cleaved soluble APP. This strong stimulatory
      effect was in the range obtained with phorbol esters and was further increased in
      cells overexpressing ADAM 10. In cells overexpressing APP, the increase of alpha
      secretase activity resulted in a decreased secretion of Abeta peptides. Several
      mechanisms were elucidated as being the basis of enhanced alpha-secretase
      activity: increased membrane fluidity and impaired internalization of APP were
      responsible for the effect observed with methyl-beta-cyclodextrin; treatment with
      lovastatin resulted in higher expression of the alpha-secretase ADAM 10. Our
      results demonstrate that cholesterol reduction promotes the nonamyloidogenic
      alpha-secretase pathway and the formation of neuroprotective alpha-secretase
      cleaved soluble APP by several mechanisms and suggest approaches to prevention of
      or therapy for Alzheimer's disease.

PMID- 11309495
TI  - An essential amino acid residue in the protein translocation channel revealed by
      targeted random mutagenesis of SecY.
AB  - The SecY/Sec61alpha family of membrane proteins are the central subunits of the
      putative protein translocation channel. We introduced random mutations into a
      segment of Escherichia coli SecY within its cytoplasmic domain 5, which was shown
      previously to be important for the SecA-dependent translocation activity.
      Mutations were classified into those retaining function and those gaining a
      dominant-interfering ability caused by a loss of function. These analyses showed
      that Arg-357, Pro-358, Gly-359, and Thr-362 are functionally important; Arg-357,
      conserved in almost all organisms, was identified as an indispensable residue.

PMID- 11309496
TI  - A new strategy to decrease N-methyl-D-aspartate (NMDA) receptor coactivation:
      inhibition of D-serine synthesis by converting serine racemase into an eliminase.
AB  - Serine racemase is a brain-enriched enzyme that synthesizes d-serine, an
      endogenous modulator of the glycine site of N-methyl-d-aspartate (NMDA)
      receptors. We now report that serine racemase catalyzes an elimination reaction
      toward a nonphysiological substrate that provides a powerful tool to study its
      neurobiological role and will be useful to develop selective enzyme inhibitors.
      Serine racemase catalyzes robust elimination of l-serine O-sulfate that is 500
      times faster than the physiological racemization reaction, generating sulfate,
      ammonia, and pyruvate. This reaction provides the most simple and sensitive assay
      to detect the enzyme activity so far. We establish stable cell lines expressing
      serine racemase and show that serine racemase can also be converted into a
      powerful eliminase in cultured cells, while the racemization of l-serine is
      inhibited. Likewise, l-serine O-sulfate inhibits the synthesis of d-serine in
      primary astrocyte cultures. We conclude that the synthetic compound l-serine O
      sulfate is a better substrate than l-serine as well as an inhibitor of d-serine
      synthesis. Inhibition of serine racemase provides a new strategy to selectively
      decrease NMDA receptor coactivation and may be useful in conditions in which
      overstimulation of NMDA receptors plays a pathological role.

PMID- 11309497
TI  - A selective peroxisome proliferator-activated receptor delta agonist promotes
      reverse cholesterol transport.
AB  - The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors
      that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects
      of the fibrate drugs and the antidiabetic effects of the glitazone drugs in
      humans are due to activation of the alpha (NR1C1) and gamma (NR1C3) subtypes,
      respectively. By contrast, the therapeutic potential of the delta (NR1C2) subtype
      is unknown, due in part to the lack of selective ligands. We have used
      combinatorial chemistry and structure-based drug design to develop a potent and
      subtype-selective PPARdelta agonist, GW501516. In macrophages, fibroblasts, and
      intestinal cells, GW501516 increases expression of the reverse cholesterol
      transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific
      cholesterol efflux. When dosed to insulin-resistant middle-aged obese rhesus
      monkeys, GW501516 causes a dramatic dose-dependent rise in serum high density
      lipoprotein cholesterol while lowering the levels of small-dense low density
      lipoprotein, fasting triglycerides, and fasting insulin. Our results suggest that
      PPARdelta agonists may be effective drugs to increase reverse cholesterol
      transport and decrease cardiovascular disease associated with the metabolic
      syndrome X.

PMID- 11309498
TI  - The optimal measure of allelic association.
AB  - Allelic association between pairs of loci is derived in terms of the association
      probability rho as a function of recombination theta, effective population size
      N, linear systematic pressure v, and time t, predicting both rho(rt), the
      decrease of association from founders and rho(ct), the increase by genetic drift,
      with rho(t) = rho(rt) + rho(ct). These results conform to the Malecot equation,
      with time replaced by distance on the genetic map, or on the physical map if
      recombination in the region is uniform. Earlier evidence suggested that rho is
      less sensitive to variations in marker allele frequencies than alternative
      metrics for which there is no probability theory. This robustness is confirmed
      for six alternatives in eight samples. In none of these 48 tests was the residual
      variance as small as for rho. Overall, efficiency was less than 80% for all
      alternatives, and less than 30% for two of them. Efficiency of alternatives did
      not increase when information was estimated simultaneously. The swept radius
      within which substantial values of rho are conserved lies between 385 and 893 kb,
      but deviation of parameters between measures is enormously significant. The large
      effort now being devoted to allelic association has little value unless the rho
      metric with the strongest theoretical basis and least sensitivity to marker
      allele frequencies is used for mapping of marker association and localization of
      disease loci.

PMID- 11309499
TI  - Significance analysis of microarrays applied to the ionizing radiation response.
AB  - Microarrays can measure the expression of thousands of genes to identify changes
      in expression between different biological states. Methods are needed to
      determine the significance of these changes while accounting for the enormous
      number of genes. We describe a method, Significance Analysis of Microarrays
      (SAM), that assigns a score to each gene on the basis of change in gene
      expression relative to the standard deviation of repeated measurements. For genes
      with scores greater than an adjustable threshold, SAM uses permutations of the
      repeated measurements to estimate the percentage of genes identified by chance,
      the false discovery rate (FDR). When the transcriptional response of human cells
      to ionizing radiation was measured by microarrays, SAM identified 34 genes that
      changed at least 1.5-fold with an estimated FDR of 12%, compared with FDRs of 60
      and 84% by using conventional methods of analysis. Of the 34 genes, 19 were
      involved in cell cycle regulation and 3 in apoptosis. Surprisingly, four
      nucleotide excision repair genes were induced, suggesting that this repair
      pathway for UV-damaged DNA might play a previously unrecognized role in repairing
      DNA damaged by ionizing radiation.

PMID- 11309500
TI  - Naturally variant autosomal and sex-linked loci determine the severity of iron
      overload in beta 2-microglobulin-deficient mice.
AB  - Hereditary hemochromatosis (HH) is a common chronic human genetic disorder whose
      hallmark is systemic iron overload. Homozygosity for a mutation in the MHC class
      I heavy chain paralogue gene HFE has been found to be a primary cause of HH.
      However, many individuals homozygous for the defective allele of HFE do not
      develop iron overload, raising the possibility that genetic variation in modifier
      loci contributes to the HH phenotype. Mice deficient in the product of the
      beta(2)-microglobulin (beta(2)M) class I light chain fail to express HFE and
      other MHC class I family proteins, and they have been found to manifest many
      characteristics of the HH phenotype. To determine whether natural genetic
      variation plays a role in controlling iron overload, we performed classical
      genetic analysis of the iron-loading phenotype in beta(2)M-deficient mice in the
      context of different genetic backgrounds. Strain background was found to be a
      major determinant in iron loading. Sex played a role that was less than that of
      strain background but still significant. Resistance and susceptibility to iron
      overload segregated as complex genetic traits in F(1) and back-cross progeny.
      These results suggest the existence of naturally variant autosomal and Y
      chromosome-linked modifier loci that, in the context of mice genetically
      predisposed by virtue of a beta(2)M deficiency, can profoundly influence the
      severity of iron loading. These results thus provide a genetic explanation for
      some of the variability of the HH phenotype.

PMID- 11309501
TI  - Selective binding of perfringolysin O derivative to cholesterol-rich membrane
      microdomains (rafts).
AB  - There is increasing evidence that sphingolipid- and cholesterol-rich microdomains
      (rafts) exist in the plasma membrane. Specific proteins assemble in these
      membrane domains and play a role in signal transduction and many other cellular
      events. Cholesterol depletion causes disassembly of the raft-associated proteins,
      suggesting an essential role of cholesterol in the structural maintenance and
      function of rafts. However, no tool has been available for the detection and
      monitoring of raft cholesterol in living cells. Here we show that a protease
      nicked and biotinylated derivative (BCtheta) of perfringolysin O (theta-toxin)
      binds selectively to cholesterol-rich microdomains of intact cells, the domains
      that fulfill the criteria of rafts. We fractionated the homogenates of nontreated
      and Triton X-100-treated platelets after incubation with BCtheta on a sucrose
      gradient. BCtheta was predominantly localized in the floating low-density
      fractions (FLDF) where cholesterol, sphingomyelin, and Src family kinases are
      enriched. Immunoelectron microscopy demonstrated that BCtheta binds to a
      subpopulation of vesicles in FLDF. Depletion of 35% cholesterol from platelets
      with cyclodextrin, which accompanied 76% reduction in cholesterol from FLDF,
      almost completely abolished BCtheta binding to FLDF. The staining patterns of
      BCtheta and filipin in human epidermoid carcinoma A431 cells with and without
      cholesterol depletion suggest that BCtheta binds to specific membrane domains on
      the cell surface, whereas filipin binding is indiscriminate to cell cholesterol.
      Furthermore, BCtheta binding does not cause any damage to cell membranes,
      indicating that BCtheta is a useful probe for the detection of membrane rafts in
      living cells.

PMID- 11309502
TI  - The 3'-->5' exonuclease of DNA polymerase delta can substitute for the 5' flap
      endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome
      instability.
AB  - Many DNA polymerases (Pol) have an intrinsic 3'-->5' exonuclease (Exo) activity
      which corrects polymerase errors and prevents mutations. We describe a role of
      the 3'-->5' Exo of Pol delta as a supplement or backup for the Rad27/Fen1 5' flap
      endonuclease. A yeast rad27 null allele was lethal in combination with Pol delta
      mutations in Exo I, Exo II, and Exo III motifs that inactivate its exonuclease,
      but it was viable with mutations in other parts of Pol delta. The rad27-p allele,
      which has little phenotypic effect by itself, was also lethal in combination with
      mutations in the Pol delta Exo I and Exo II motifs. However, rad27-p Pol delta
      Exo III double mutants were viable. They exhibited strong synergistic increases
      in CAN1 duplication mutations, intrachromosomal and interchromosomal
      recombination, and required the wild-type double-strand break repair genes RAD50,
      RAD51, and RAD52 for viability. Observed effects were similar to those of the
      rad27-null mutant deficient in the removal of 5' flaps in the lagging strand.
      These results suggest that the 3'-->5' Exo activity of Pol delta is redundant
      with Rad27/Fen1 for creating ligatable nicks between adjacent Okazaki fragments,
      possibly by reducing the amount of strand-displacement in the lagging strand.

PMID- 11309503
TI  - Dynamics of mobile element activity in chalcone synthase loci in the common
      morning glory (Ipomoea purpurea).
AB  - Mobile element dynamics in seven alleles of the chalcone synthase D locus (CHS-D)
      of the common morning glory (Ipomoea purpurea) are analyzed in the context of
      synonymous nucleotide sequence distances for CHS-D exons. By using a nucleotide
      sequence of CHS-D from the sister species Ipomoea nil (Japanese morning glory
      [Johzuka-Hisatomi, Y., Hoshino, A., Mori, T., Habu, Y. & Iida, S. (1999) Genes
      Genet. Syst. 74, 141-147], it is also possible to determine the relative
      frequency of insertion and loss of elements within the CHS-D locus between these
      two species. At least four different types of transposable elements exist
      upstream of the coding region, or within the single intron of the CHS-D locus in
      I. purpurea. There are three distinct families of miniature inverted-repeat
      transposable elements (MITES), and some recent transpositions of
      Activator/Dissociation (Ac/Ds)-like elements (Tip100), of some short interspersed
      repetitive elements (SINEs), and of an insertion sequence (InsIpCHSD) found in
      the neighborhood of this locus. The data provide no compelling evidence of the
      transposition of the mites since the separation of I. nil and I. purpurea roughly
      8 million years ago. Finally, it is shown that the number and frequency of mobile
      elements are highly heterogeneous among different duplicate CHS loci, suggesting
      that the dynamics observed at CHS-D are locus-specific.

PMID- 11309504
TI  - Characterization of a high-voltage-activated IA current with a role in spike
      timing and locomotor pattern generation.
AB  - Transient A-type K+ channels (I(A)) in neurons have been implicated in the delay
      of the spike onset and the decrease in the firing frequency. Here we have
      characterized biophysically and pharmacologically an I(A) current in lamprey
      locomotor network neurons that is activated by suprathreshold depolarization and
      is specifically blocked by catechol at 100 microM. The biophysical properties of
      this current are similar to the mammalian Kv3.4 channel. The role of the I(A)
      current both in single neuron firing and in locomotor pattern generation was
      analyzed. The I(A) current facilitates Na+ channel recovery from inactivation and
      thus sustains repetitive firing. The role of the I(A) current in motor pattern
      generation was examined by applying catechol during fictive locomotion induced by
      N-methyl-d-aspartate. Blockade of this current increased the locomotor burst
      frequency and decreased the firing of motoneurons. Although an alternating motor
      pattern could still be generated, the cycle duration was less regular, with
      ventral roots bursts failing on some cycles. Our results thus provide insights
      into the contribution of a high-voltage-activated I(A) current to the regulation
      of firing properties and motor coordination in the lamprey spinal cord.

PMID- 11309505
TI  - Defective regulatory volume decrease in human cystic fibrosis tracheal cells
      because of altered regulation of intermediate conductance Ca2+-dependent
      potassium channels.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) protein has the
      ability to function as both a chloride channel and a channel regulator. The loss
      of these functions explains many of the manifestations of the cystic fibrosis
      disease (CF), including lung and pancreatic failure, meconium ileus, and male
      infertility. CFTR has previously been implicated in the cell regulatory volume
      decrease (RVD) response after hypotonic shocks in murine small intestine crypts,
      an effect associated to the dysfunction of an unknown swelling-activated
      potassium conductance. In the present study, we investigated the RVD response in
      human tracheal CF epithelium and the nature of the volume-sensitive potassium
      channel affected. Neither the human tracheal cell line CFT1, expressing the
      mutant CFTR-DeltaF508 gene, nor the isogenic vector control line CFT1-LC3,
      engineered to express the betagal gene, showed RVD. On the other hand, the cell
      line CFT1-LCFSN, engineered to express the wild-type CFTR gene, presented a full
      RVD. Patch-clamp studies of swelling-activated potassium currents in the three
      cell lines revealed that all of them possess a potassium current with the
      biophysical and pharmacological fingerprints of the intermediate conductance
      Ca(2+)-dependent potassium channel (IK, also known as KCNN4). However, only CFT1
      LCFSN cells showed an increase in IK currents in response to hypotonic
      challenges. Although the identification of the molecular mechanism relating CFTR
      to the hIK channel remains to be solved, these data offer new evidence on the
      complex integration of CFTR in the cells where it is expressed.

PMID- 11309506
TI  - Oncogenic ras activates the ARF-p53 pathway to suppress epithelial cell
      transformation.
AB  - Chemically induced skin carcinomas in mice are a paradigm for epithelial
      neoplasia, where oncogenic ras mutations precede p53 and INK4a/ARF mutations
      during the progression toward malignancy. To explore the biological basis for
      these genetic interactions, we studied cellular responses to oncogenic ras in
      primary murine keratinocytes. In wild-type keratinocytes, ras induced a cell
      cycle arrest that displayed some features of terminal differentiation and was
      accompanied by increased expression of the p19(ARF), p16(INK4a), and p53 tumor
      suppressors. In ARF-null keratinocytes, ras was unable to promote cell-cycle
      arrest, induce differentiation markers, or properly activate p53. Although
      oncogenic ras produced a substantial increase in both nucleolar and nucleoplasmic
      p19(ARF), Mdm2 did not relocalize to the nucleolus or to nuclear bodies but
      remained distributed throughout the nucleoplasm. This result suggests that
      p19(ARF) can activate p53 without overtly affecting Mdm2 subcellular
      localization. Nevertheless, like p53-null keratinocytes, ARF-null keratinocytes
      were transformed by oncogenic ras and rapidly formed carcinomas in vivo. Thus,
      oncogenic ras can activate the ARF-p53 program to suppress epithelial cell
      transformation. Disruption of this program may be important during skin
      carcinogenesis and the development of other carcinomas.

PMID- 11309508
TI  - Genetic documentation of filial cannibalism in nature.
AB  - Cannibalism is widespread in natural populations of fishes, where the stomachs of
      adults frequently contain conspecific juveniles. Furthermore, field observations
      suggest that guardian males routinely eat offspring from their own nests.
      However, recent genetic paternity analyses have shown that fish nests often
      contain embryos not sired by the nest-tending male (because of cuckoldry events,
      egg thievery, or nest piracy). Such findings, coupled with the fact that several
      fish species have known capabilities for distinguishing kin from nonkin, raise
      the possibility that cannibalism by guardian males is directed primarily or
      exclusively toward unrelated embryos in their nests. Here, we test this
      hypothesis by collecting freshly cannibalized embryos from the stomachs of
      several nest-tending darter and sunfish males in nature and determining their
      genetic parentage by using polymorphic microsatellite markers. Our molecular
      results clearly indicate that guardian males do indeed consume their own genetic
      offspring, even when unrelated (foster) embryos are present within the nest.
      These data provide genetic documentation of filial cannibalism in nature.
      Furthermore, they suggest that the phenomenon may result, at least in part, from
      an inability of guardians to differentiate between kin and nonkin within their
      own nests.

PMID- 11309507
TI  - Tumor necrosis factor-related apoptosis-inducing ligand in T cell development:
      sensitivity of human thymocytes.
AB  - TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a recently
      identified member of the tumor necrosis factor cytokine superfamily. TRAIL has
      been shown to induce apoptosis in various tumor cell lines, whereas most primary
      cells seem to be resistant. These observations have raised considerable interest
      in the use of TRAIL in tumor therapy. Yet little is known about the physiological
      function of TRAIL. This is particularly the case in the immune system, where
      TRAIL has been suggested by some to be involved in target cell killing and
      lymphocyte death. We have developed a panel of mAbs and soluble proteins to
      address the role of TRAIL in lymphocyte development. These studies demonstrate
      activation-induced sensitization of thymocytes to TRAIL-mediated apoptosis and
      expression of the apoptosis-inducing TRAIL receptors. However, with the use of
      several model systems, our subsequent experiments rule out the possibility that
      TRAIL plays a major role in antigen-induced deletion of thymocytes. In contrast
      to thymocytes, there is no up-regulation of TRAIL receptors in peripheral T cells
      on activation, which remain resistant to TRAIL. Thus, susceptibility to TRAIL
      induced apoptosis is controlled differently by central and peripheral T cells.

PMID- 11309509
TI  - Complex mtDNA constitutes an approximate 620-kb insertion on Arabidopsis thaliana
      chromosome 2: implication of potential sequencing errors caused by large-unit
      repeats.
AB  - Previously conducted sequence analysis of Arabidopsis thaliana (ecotype Columbia
      0) reported an insertion of 270-kb mtDNA into the pericentric region on the short
      arm of chromosome 2. DNA fiber-based fluorescence in situ hybridization analyses
      reveal that the mtDNA insert is 618 +/- 42 kb, approximately 2.3 times greater
      than that determined by contig assembly and sequencing analysis. Portions of the
      mitochondrial genome previously believed to be absent were identified within the
      insert. Sections of the mtDNA are repeated throughout the insert. The cytological
      data illustrate that DNA contig assembly by using bacterial artificial
      chromosomes tends to produce a minimal clone path by skipping over duplicated
      regions, thereby resulting in sequencing errors. We demonstrate that fiber
      fluorescence in situ hybridization is a powerful technique to analyze large
      repetitive regions in the higher eukaryotic genomes and is a valuable complement
      to ongoing large genome sequencing projects.

PMID- 11309510
TI  - Anti-mosquito midgut antibodies block development of Plasmodium falciparum and
      Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector
      fecundity and survivorship.
AB  - The mosquito midgut plays a central role in the sporogonic development of malaria
      parasites. We have found that polyclonal sera, produced against mosquito midguts,
      blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading
      to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were
      produced that display broad-spectrum activity, blocking parasite development of
      both P. falciparum and Plasmodium vivax parasites in five different species of
      mosquitoes. In addition to their parasite transmission-blocking activity, these
      mAbs also reduced mosquito survivorship and fecundity. These results reveal that
      mosquito midgut-based antibodies have the potential to reduce malaria
      transmission in a synergistic manner by lowering both vector competence, through
      transmission-blocking effects on parasite development, and vector abundance, by
      decreasing mosquito survivorship and egg laying capacity. Because the
      intervention can block transmission of different malaria parasite species in
      various species of mosquitoes, vaccines against such midgut receptors may block
      malaria transmission worldwide.

PMID- 11309511
TI  - The Cia5 gene controls formation of the carbon concentrating mechanism in
      Chlamydomonas reinhardtii.
AB  - Wild-type Chlamydomonas reinhardtii cells shifted from high concentrations (5%)
      of CO2 to low, ambient levels (0.03%) rapidly increase transcription of mRNAs
      from several CO2-responsive genes. Simultaneously, they develop a functional
      carbon concentrating mechanism that allows the cells to greatly increase internal
      levels of CO2 and HCO3-. The cia5 mutant is defective in all of these phenotypes.
      A newly isolated gene, designated Cia5, restores transformed cia5 cells to the
      phenotype of wild-type cells. The 6,481-bp gene produces a 5.1-kb mRNA that is
      present constitutively in light in high and low CO2 both in wild-type cells and
      the cia5 mutant. It encodes a protein that has features of a putative
      transcription factor and that, likewise, is present constitutively in low and
      high CO2 conditions. Complementation of cia5 can be achieved with a truncated
      Cia5 gene that is missing the coding information for 54 C-terminal amino acids.
      Unlike wild-type cells or cia5 mutants transformed with an intact Cia5 gene, cia5
      mutants complemented with the truncated gene exhibit constitutive synthesis of
      mRNAs from CO2-responsive genes in light under both high and low CO2 conditions.
      These discoveries suggest that posttranslational changes to the C-terminal domain
      control the ability of CIA5 to act as an inducer and directly or indirectly
      control transcription of CO2-responsive genes. Thus, CIA5 appears to be a master
      regulator of the carbon concentrating mechanism and is intimately involved in the
      signal transduction mechanism that senses and allows immediate responses to
      fluctuations in environmental CO2 and HCO3- concentrations.

PMID- 11309512
TI  - Selective association of the methyl-CpG binding protein MBD2 with the silent
      p14/p16 locus in human neoplasia.
AB  - DNA methylation of tumor suppressor genes is a common feature of human cancer.
      The cyclin-dependent kinase inhibitor gene p16/Ink4A is hypermethylated in a wide
      range of malignant tissues and the p14/ARF gene located 20 kb upstream on
      chromosome 9p21 is also methylated in carcinomas. p14/ARF (ARF, alternative
      reading frame) does not inhibit the activities of cyclins or cyclin-dependent
      kinase complexes; however, the importance of the two gene products in the
      etiology of cancer resides in their involvement in two major cell cycle
      regulatory pathways: p53 and the retinoblastoma protein, Rb, respectively.
      Distinct first exons driven from separate promoters are spliced onto the common
      exons 2 and 3 and the resulting proteins are translated in different reading
      frames. Both genes are expressed in normal cells but can be alternatively or
      coordinately silenced when their CpG islands are hypermethylated. Herein, we
      examined the presence of methyl-CpG binding proteins associated with aberrantly
      methylated promoters, the distribution of acetylated histones H3 and H4 by
      chromatin immunoprecipitation assays, and the effect of chemical treatment with 5
      aza-2'-deoxycytidine (5aza-dC) and trichostatin A on gene induction in colon cell
      lines by quantitative reverse transcriptase-PCR. We observed that the methyl-CpG
      binding protein MBD2 is targeted to methylated regulatory regions and excludes
      the acetylated histones H3 and H4, resulting in a localized inactive chromatin
      configuration. When methylated, the genes can be induced by 5aza-dC but the
      combined action of 5aza-dC and trichostatin A results in robust gene expression.
      Thus, methyl-CpG binding proteins and histone deacetylases appear to cooperate in
      vivo, with a dominant effect of DNA methylation toward histone acetylation, and
      repress expression of tumor suppressor genes hypermethylated in cancers.

PMID- 11309513
TI  - Balanced branching in transcription termination.
AB  - The theory of stochastic transcription termination based on free-energy
      competition [von Hippel, P. H. & Yager, T. D. (1992) Science 255, 809-812 and von
      Hippel, P. H. & Yager, T. D. (1991) Proc. Natl. Acad. Sci. USA 88, 2307-2311]
      requires two or more reaction rates to be delicately balanced over a wide range
      of physical conditions. A large body of work on glasses and large molecules
      suggests that this balancing should be impossible in such a large system in the
      absence of a new organizing principle of matter. We review the experimental
      literature of termination and find no evidence for such a principle, but do find
      many troubling inconsistencies, most notably, anomalous memory effects. These
      effects suggest that termination has a deterministic component and may
      conceivably not be stochastic at all. We find that a key experiment by Wilson and
      von Hippel [Wilson, K. S. & von Hippel, P. H. (1994) J. Mol. Biol. 244, 36-51]
      thought to demonstrate stochastic termination was an incorrectly analyzed
      regulatory effect of Mg(2+) binding.

PMID- 11309514
TI  - Regression to the mean: what does it mean? Using bone density results to monitor
      treatment of osteoporosis.

PMID- 11309515
TI  - Effect of parathyroid hormone (hPTH[1-84]) treatment on bone mass and strength in
      ovariectomized rats.
AB  - Skeletal fragility in osteoporotic patients is a prominent underlying cause of
      low-trauma fractures of most bone sites in humans. Clinical research is now
      focused on developing treatment strategies, including anabolic agents such as
      parathyroid hormone (PTH), to recover osteoporosis-related bone loss. Female
      Sprague-Dawley rats (4.5 mo old) were allowed to become osteopenic for 10 wk
      postovariectomy. Eight rats were killed at the time of ovariectomy (-10 wk) as a
      baseline control; sham and ovariectomized (OVX) groups were killed at wk 0. Eight
      rats per group (sham, OVX + vehicle, OVX + hPTH [5 d/wk], and OVX + hPTH [3
      d/wk]) were killed after 4, 8, 14, and 20 wk of treatment with 50 microg/kg of
      human parathyroid hormone (hPTH[1-84]). Bone mineral content and density were
      measured only in the vertebral body. Bone strength was evaluated in the vertebral
      body, femoral diaphysis, femoral neck, and distal femur. Significant, lasting
      osteopenia developed in the vertebral body of OVX rats by 10 wk postovariectomy.
      Bone mineral density of the vertebral body partially recovered by 8 wk and fully
      recovered to that seen in sham animals only by 20 wk posttreatment with either a
      5 or 3 d/wk dosing schedule of PTH[1-84]. Therefore, hPTH[1-84] (50 microg/kg)
      given either 3 or 5 d/wk fully restores vertebral and femoral bone strength in
      osteopenic OVX rats.

PMID- 11309516
TI  - Prevalence of low bone density in women with developmental disabilities.
AB  - This study was designed to assess the prevalence and severity of low bone mineral
      density in an institutionalized population of postmenopausal women (n = 79) with
      developmental disabilities, using quantitative ultrasound of the calcaneus. The
      results demonstrate that this population has a significantly lower quantitative
      ultrasound index (QUI) of the calcaneus compared with a referent population of
      age-matched control subjects without mental disabilities. We used the QUI T-score
      threshold of <-2.0 standard deviations (SDs) to define individuals at high risk
      for osteoporosis, and 82% of the study participants met this criterion.
      Furthermore, approx 43% of the population had a heel QUI that was more than 2 SDs
      below that of age-matched control subjects, consistent with a severe degree of
      demineralization.

PMID- 11309517
TI  - Linear correlation between axial and lateral bone mineral density of lumbar
      vertebrae.
AB  - The placement of most spinal interbody devices is above the cancellous region of
      the vertebral bodies. Dual X-ray absorptiometry (DXA) scans of patients are
      usually taken from the anterior-posterior or the lateral projection. DXA scans
      taken in vitro from the axial direction would most closely indicate the bone
      mineral density (BMD) of the bone at this region. So far, in vitro studies have
      not been conducted to determine the correlation between axial and lateral scans.
      Because lateral DXA BMD scans are noninvasive and have low radiation dosage, they
      could be used as a predictive tool to determine the quality of cancellous bone at
      the centrum of the vertebral bodies, where spinal interbody devices are commonly
      placed.

PMID- 11309518
TI  - Bilateral variation in calcaneal broadband ultrasound attenuation: part I.
AB  - A total of 1412 women of various ethnic origins ages 20-80 yr were tested for
      bilateral calcaneal broad-band ultrasound attenuation (BUA) with the McCue
      Cubaclinical ultrasound bone densitometer. A significant difference was found
      between nondominant and dominant measures (p < 0.0001). The magnitude of
      calcaneal BUA was not related to dominance. The difference was of a significant
      degree to have resulted in differing predictions of fracture risk depending on
      the side used in assessment. Forty-eight subjects (3%) would have been considered
      at risk of osteoporotic fracture based on the nondominant measure, whereas only
      21 subjects (1.5%) would have been considered to be at risk based on the dominant
      measure. In concurrence with other studies, we conclude that it is essential to
      carry out bilateral measurements of the os calcis to avoid misleading
      implications for prediction of fracture risk.

PMID- 11309519
TI  - Longitudinal study of age- and menopause-related metacarpal index changes in
      Japanese adult females.
AB  - To establish a comprehensive mode for cortical bone thinning rate, the metacarpal
      index (MCI) of the index finger of the nondominant hand was measured using
      computed X-ray microdensitometry. Statistical analysis was used to study the MCI
      data in relation to age and menopausal status. A total of 383 healthy Japanese
      women ranging in age from 30 to 79 yr were investigated in 1996 and 1999. The MCI
      was generally decreased by 1.11% per year. However, accelerative decreases of
      1.78 and 2.05% per year were observed within both the age 50-59 yr group and the
      early postmenopausal period, respectively. In addition, analysis of age-based
      longitudinal data showed that the age-related loss of MCI in the age 50-59 yr
      category was significantly higher than that in the other age categories (p <
      0.01), indicating that the changes in MCI were more dependent on menopausal
      status than on aging. Our study suggests that the cortical bone thinning rate is
      affected by both aging and menopausal status, but the latter may be a predominant
      factor.

PMID- 11309520
TI  - Quantitative computed tomography of spine: comparison of three-dimensional and
      two-dimensional imaging approaches in clinical practice.
AB  - Quantitative computed tomography (QCT), a widely utilized technique for
      determining bone mineral density (BMD) at various skeletal sites, may yield less
      precise measurements if there are operator measurement errors and other technical
      variables. Two-dimensional (2D)and three-dimensional (3D)QCT scans of the lumbar
      spine of 21 women were compared in order to investigate the effects of potential
      operator variability on the precision of BMD measurements and to examine
      resulting differences of these imaging approaches in clinical practice. No
      significant difference was found (p > 0.05) in precision between the 2D and 3D
      QCT BMD measurements owing to operator measurement errors on the CT scans. The
      variability in BMD values within numerous small regions of interest (ROIs)(
      approximately 75 mm (2) ) of cancellous bone within a single vertebra was 10.1%,
      larger than the 2D or 3D BMD variability measured in typical regions (
      approximately 250 mm (2)) by an order of magnitude. 3D BMD values in this
      population, which represented a wide range of clinical values, were found to be
      significantly greater than 2D BMD values by an average of 5.6% (p = 0.00024)
      relative to the 2D QCT values. Our findings suggest technical measurement error
      does not have a significant effect on precision of BMD measurements obtained with
      either QCT method. Several factors, however, including the incorporation of focal
      regions of higher density bone mass within the 3D QCT ROI may account for the
      higher BMD values compared with those for 2D QCT.

PMID- 11309521
TI  - Diagnostic discrepancies between two closely related forearm bone density
      measurement sites.
AB  - At the present time the diagnosis of osteoporosis is based on the use of T
      scores. Measurements at different skeletal sites or of different regions of
      interest may result in diagnostic discrepancies. In this study, we tried to
      demonstrate that bone mineral density (BMD)values at the closely related forearm
      sites may lead to diagnostic uncertainty, and to assess the degree of site
      heterogeneity across different age groups. The study consisted of 2348 women (age
      20-83) referred for bone densitometry. Forearm BMD was measured at the distal and
      ultradistal sites by single X-ray absorptiometry (DTX-100 device). T-scores were
      calculated from Bulgarian reference data. Diagnostic disagreement between sites
      was found in 19.3% of all women. In 7.7% of all cases, the difference between T
      scores at the two sites exceeded 1. The discrepancies were more pronounced after
      age 60. This corresponds well to the different onset and rates of trabecular and
      cortical bone losses as well as to their different distribution along the
      forearm. We encourage the separate assessment of cortical and trabecular bone
      densities or measurements at axial sites in case forearm sites yield conflicting
      results or low-normal BMD values.

PMID- 11309522
TI  - Peak bone mass, reference values, and T-scores.

PMID- 11309524
TI  - Use of an Animal Model in Studies of Bacterial Corneal Infection.
AB  - Despite medical advancements in available therapies, bacterial corneal infection
      frequently results in vision loss. Contact lens wear is a common predisposing
      factor for corneal infection; other reported risk factors are dry eye syndrome,
      blepharitis, trauma, and surgery. Both the immune defense against infection and
      the pathogenic mechanisms bacteria employ have been studied in vitro. However,
      there are complex interactions between the pathogen, the immune system, and the
      corneal tissue in vivo. Animal models allow the researcher to take the results of
      in vitro assays and validate their role in corneal infection in a living
      organism. A murine model is frequently used for studies of the pathogenesis of
      corneal infection caused by Pseudomonas aeruginosa. In this study, a modified
      scoring system is introduced that was designed to increase the information
      derived from this infection model. The new system includes evaluation of area,
      density, and surface characteristics of the ulceration. Results of in vitro
      experiments had previously indicated that ExsA, a transcriptional regulator of
      virulence-associated proteins, was important in pathogenesis of corneal infection
      caused by P. aeruginosa. Here we use the new scoring system to demonstrate in
      vivo that ExsA is involved.

PMID- 11309526
TI  - Recent insights into the role of tumor necrosis factor in the failing heart.
AB  - Recent studies have identified the importance of biologically active molecules
      such as neurohormones in disease progression in heart failure. More recently it
      has become apparent that in addition to neurohormones, another portfolio of
      biologically active molecules termed cytokines, are also expressed in the setting
      of heart failure. This article will review recent clinical and experimental
      material which suggests that tumor necrosis factor (TNF), a pro-inflammatory
      cytokine, may contribute to disease progression in heart failure by virtue of the
      direct toxic effects that this molecule exerts on the heart and circulation.

PMID- 11309527
TI  - The role of interleukin-1 in the failing heart.
AB  - The prevalence of congestive heart failure and its continued poor prognosis
      despite presently available therapeutic options emphasize the importance of
      pursuing the observations suggesting an important role for an immunomodulatory
      approach to decompensated cardiac failure. Furthermore, there are several pieces
      of background information that suggest that cytokines like IL-1 may play a
      significant role in the pathogenesis of several forms of myocardial dysfunction.
      Although it seems clear that IL-1 is not acting alone under circumstances of
      myocardial injury, but in concert with other pro-inflammatory molecules and their
      effectors, we believe that continued investigations into the cytokine hypothesis
      will ultimately increase the understanding of how pro-inflammatory molecules
      influence myocardial function and how the modulation of such factors may improve
      the myocardial response to injury. The specific observations that emphasize the
      importance of pursuing a substantive role for IL-1 in this process are: (1) IL-1
      is elevated in several cardiac disease states, (2) IL-1 is produced by myocardial
      cells themselves in response to injury, (3)The alterations in gene expression
      seen in response IL-1 resembles in many ways the phenotype of the failing heart,
      and (4) The co-localization of the IL-1 response with that of several previously
      described negative transcriptional regulators (making them potential targets for
      therapeutic manipulation).

PMID- 11309528
TI  - The role of interleukin-6 in the failing heart.
AB  - Clinical studies have shown that circulating levels of interleukin (IL)-6 and
      other IL-6 related cytokines are increased in patients with congestive heart
      failure (CHF). Plasma IL-6 concentrations are related to decreasing functional
      status of the patient and provide important prognostic information. Experimental
      studies have produced compelling evidence that IL-6 and IL-6 related cytokines
      play a pivotal role in the regulation of cardiac myocyte hypertrophy and
      apoptosis. This review summarizes clinical and experimental data from this
      rapidly evolving field, which, taken together, strongly suggest that IL-6 and IL
      6 related cytokines are intricately involved in the pathophysiology of the
      failing heart.

PMID- 11309529
TI  - The role of nitric oxide in the failing heart.
AB  - Nitric oxide (NO) has effects on contractility, energetics and gene expression of
      failing myocardium. Initial studies on isolated cardiomyocytes showed NO to
      reduce systolic shortening but intracoronary infusions of NO-donors or of NO
      synthase (NOS) inhibitors failed to elicit changes in baseline LV contractility
      indices such as LVdP/dt(max). Intracoronary infusions of NO-donors or of
      substance P, which releases NO from the coronary endothelium, however
      demonstrated NO to induce a downward displacement of the left ventricular (LV)
      diastolic pressure-volume relation, consistent with increased LV diastolic
      distensibility. In end-stage failing myocardium, the increased oxygen consumption
      is related to reduced NO production and in isolated cardiomyocytes, NO blunts the
      norepinephrine-induced expression of the fetal gene programme thereby preserving
      myocardial calcium homeostasis.In dilated cardiomyopathy, changed endomyocardial
      NOS gene expression has been reported. Because of lower endomyocardial NOS gene
      expression in patients with higher functional class and lower LV stroke work,
      increased endomyocardial NOS gene expression seems to be beneficial rather than
      detrimental for the failing heart. A beneficial effect of increased NOS gene
      expression could result from NO's ability to increase LV diastolic
      distensibility, to augment LV preload reserve, to reduce myocardial oxygen
      consumption and to prevent downregulation of calcium ATPase. Upregulated
      endomyocardial NOS gene expression has also been reported in athlete's heart and
      could therefore play a role in physiological LV remodeling. Reduced
      endomyocardial NO content because of decreased NO or increased superoxide
      production could lower LV diastolic distensibility and contribute to diastolic
      heart failure. In many conditions such as aging, hypertension, diabetes or
      posttransplantation, the increased incidence of diastolic heart failure is indeed
      paralleled by reduced endothelium-dependent vasodilation.

PMID- 11309530
TI  - Interactions between cytokines and neurohormonal systems in the failing heart.
AB  - The prognosis for patients with congestive heart failure (CHF) has been improved
      as a result of the use of angiotensin converting enzyme inhibitors and beta
      adrenergic receptor blockers. The success of these therapies underscores the
      pathogenic role of neurohormonal activation in CHF. Clinical and experimental
      evidence supports a pathophysiologic role for pro-inflammatory cytokines and
      nitric oxide (NO) in the effects of angiotensin II and norepinephrine in CHF.
      Potential mechanism(s) responsible for the effects of these immunomodulators can
      be explained on the basis of established principles of myocardial excitation
      contraction coupling (E-C). A novel hypothesis is proposed that cytokines and NO
      mediated alterations in E-C coupling contribute to the reversible myocardial
      depression and beta-adrenergic desensitization observed in a diverse group of
      clinical conditions that activate host inflammatory responses, including CHF.
      Basic studies into cytokine signaling pathways in cardiac myocytes have the
      potential to provide important new insights relevant to the design of new
      management strategies for the treatment of congestive heart failure patients.

PMID- 11309531
TI  - The role of inflammatory mediators in the failing heart: immunomodulation of
      cytokines in experimental models of heart failure.
AB  - Congestive heart failure may be produced by a variety of disorders, including
      dilated cardiomyopathy, hypertension, and ischemic heart disease. We have
      developed experimental models of these diseases, and found gene expressions of
      proinflammatory cytokines increased in the hearts of these animals. Various drugs
      for heart failure modulate the production of cytokines in experimental models of
      heart failure. Pimobendan, an inhibitor of phosphodiesterase III prolonged
      survival, attenuated inflammatory lesions, and decreased the production of
      cytokines and nitric oxide. Recent studies have shown that these inhibitory
      effects are due to inhibition of activation of NF-kappaB. In contrast, digitalis
      increased the production of cytokines and exacerbated myocarditis. Interleukin-10
      prolonged survival, attenuated myocardial injury, and appears promising as a
      treatment of heart failure due to viral myocarditis. Endothelin-1 plays an
      important pathophysiological role in heart failure, and treatment with an
      endothelin antagonist had a cardioprotective effect in experimental models of
      heart failure.

PMID- 11309532
TI  - The effect of cytokines on cardiac allograft function: tumor necrosis factor
      alpha a mediator of chronic injury.

PMID- 11309533
TI  - The role of anti-cytokine therapy in the failing heart.
AB  - The understanding of the role of "neurohormones" in the progression of heart
      failure has led to the utilization of agents that antagonize the activation of
      neurohormonal systems as effective therapy in patients with heart failure. As
      more evidence emerges linking proinflammatory cytokines to disease progression in
      heart failure, there is an increasing interest in developing anti-cytokine
      strategies that might be used as adjunctive therapy in patients with heart
      failure. Accordingly, the focus of the present review is to summarize the
      experimental and clinical studies that have attempted to modulate the effects of
      cytokines in heart failure. Strategies have been employed to either suppress
      cytokine production or to prevent their toxic effects by interfering with the
      binding of cytokines to their cognate receptors.

PMID- 11309534
TI  - A combination of fluticasone and salmeterol for asthma.

PMID- 11309535
TI  - Topical tacrolimus for treatment of atopic dermatitis.

PMID- 11309536
TI  - Serum IgD levels in children with atopic asthma. A longitudinal study.
AB  - BACKGROUND: Serum IgD and IgE levels were measured in children with atopic asthma
      and in control Group in order to determine their relationship with clinical
      status. METHODS: Samples of venous blood (of 5 cc) were drawn from 25 asthmatic
      children (Group A) and 25 healthy children (Group B) at the moment of first
      diagnosis (T0), after 6 months (T180) and after 18 months (T540). To measure IgD,
      an ELISA assay based on the  sandwich  principle was used. RESULTS: At T0, IgD
      were significantly higher in Group A (182.7 5+/-88.18 IU/ml) in comparison with
      Group B (69.58+/-4.93 IU/ml, p<0.0001); IgD levels decreased in Group A at T540.
      CONCLUSIONS: In conclusion, a significant increase of IgD levels observed in
      children at first signs of asthma and the following normalization of these same
      levels after 18 months, may represent a non specific response or an attempt of
      the organism to block asthma, favouring therefore immunologic tolerance.

PMID- 11309537
TI  - Flat and cavus foot, indexes of obesity and overweight in a population of primary
      school children.
AB  - BACKGROUND: Obesity and overweight during the developmental years are related to
      certain dysmorphisms of the foot, in particular with flat foot. METHODS: The
      authors evaluated the incidence of this dysmorphism in a population of 243
      primary-school pupils, (3rd and 4th class - age range 8-10 years) of ULSS no. 16
      in Padua and, at the same time, determined the index of overweight and obesity
      and the extent and quality of exercise practised. From the anthropometric data
      collected, it was calculated that the Cole index (ideal ratio between the ideal
      BMI at the 50 degrees percentile of weight and height as a function of age, sex
      and real BMI). A photo-podoscopic examination was done in a bipodalic station and
      the report analysed later on a Polaroid photograph. RESULTS: The incidence of
      flat foot in the population studied was found to be 16.4%, of which 18.1% were
      males and 14.6% females. Fifty percent showed slight flat-footedness (1st
      degree), 28% moderate (2nd degree) and 22% showed very marked flat-footedness
      (3rd degree). The frequency of obesity and overweight in the same population was
      found to be 27.3% (Cole index >120). An analysis of the variance showed a
      significant difference between the Cole Index in subjects with flat feet
      (121.77+/-19.2) and the rest of the population examined (110.12+/-15.3)
      (p<.00001). CONCLUSIONS: In this study, the children suffering from this
      dysmorphism were also found to be obese or overweight.

PMID- 11309538
TI  - [Zonula occludens toxin: an innovative method of oral drugs delivery].
AB  - Conventional forms of administration of nonabsorbable drugs and peptides often
      rely on parenteral injection, because the intestinal epithelium represents a
      major barrier to the oral absorption of these therapeutical agents into the
      systemic circulation. Recently, a number of innovative drug-delivery approaches
      have been developed, including drug entrapment within small vesicles or the
      passage of the therapeutic molecules through the space between adjacent
      intestinal cells. This article reviews some of the most promising techniques
      currently available for oral delivery and their possible practical applications
      for the delivery of vaccines and drugs for the treatment of clinical conditions
      that require frequent, chronic parenteral administration.

PMID- 11309539
TI  - The 4P-syndrome. Case description and literature review.
AB  - The microdeletion 4p16 has been found in two rare syndromes. Until now they were
      considered as two different syndromes: the Wolf-Hirschhorn syndrome (WHS) and the
      Pitt-Rogers-Danks (PRDS) syndrome characterized by a growth retardation before
      and after birth, microcrania, seizures, characteristic face with thin mouth,
      maxillary hypoplasia, short and large philtrum, characteristic nose and mental
      retardation. A case with 4p-16 microdeletion with phenotype characteristics
      similar to PRDS is reported. The patients described as PRDS are sometimes less
      seriously affected than patients with WHS. In fact, cases of death are not
      indicated in the first year of life, internal malformations are less frequent and
      the face lacks the typical Greek warrior helmet Recent studies have shown that
      WSS and PRDS are due to the absence of similar if not identical genetic segments
      and the clinical differences observed could be the outcome of an allele variation
      on the remaining homologous part.

PMID- 11309540
TI  - [Tinea faciei in a newborn].
AB  - Dermatophytosis in newborns and infants has been regarded as very unusual; a case
      recently observed of a 2-month-old child affected by tinea faciei is described.
      Twenty days before, localized erythematous infiltrated patches at the upper left
      eyelid and eyebrows with papules and pustules, were observed. Rarefaction of the
      eyebrows and partially loss of the eyelashes associated with scattered areas of
      erythematopapulous lesions on the face, were seen. Mycological examination was
      positive and trichophyton rubrum colonies grew. Tinea capitis is more common than
      tinea faciei in newborn and infants. Differential diagnosis includes: seborrheic
      dermatitis, atopic dermatitis with associated impetigo, candidiasis, bacterial
      folliculitis. The interhuman transmission by relatives is the most probable
      modality of trans-mission, as previously reported in the literature. A widespread
      of the dermatoses was due to previous application of topical corticosteroids. The
      lesions resolved completely after treatment with miconazole cream, applied twice
      daily for three weeks.

PMID- 11309541
TI  - [A case of acute lymphoblastic leukemia with an unusual presentation and slow
      development].
AB  - The authors describe the case of a 3-year-old girl with acute lymphoblastic
      leukemia which was diagnosed several months after the appearance of the first
      symptoms. The delay can be attributed to the vague symptoms at onset in the form
      of a single laterocervical adenopathy which responded to antibiotic and
      antiphlogistic therapy, the total absence of any indicative hematological
      symptoms and the patient s persistent excellent general conditions. In the light
      of this unusual case, the authors stress the need to carry out invasive
      diagnostic tests on lymph node lesions that are often defined as  aspecific 
      given that they may occasionally disguise more severe lymphoproliferative
      diseases.

PMID- 11309542
TI  - Niikawa-Kuroki (Kabuki) syndrome in two siblings.
AB  - The Niikawa-Kuroki (Kabuki make-up) syndrome is a recognizable pattern of
      malformation consisting of mental retardation, dysmorphic cranio-facial features,
      bone and joint anomalies, postnatal growth deficiency and susceptibility to
      infections. Two male siblings, 8 and 5 years of age, displaying characteristic
      clinical and radiological manifestations of this syndrome as well as their
      father, who displays only some of the facial features, are presented.

PMID- 11309543
TI  - [Legal and medico-legal issues in adolescent medicine. A critical review of the
      present regulation and legislation].
AB  - During the last years the Italian Government has taken many different initiatives
      to protect the adolescents  rights to benefit from physical, psychical and social
      well-being. In particular, various projects concerning the promotion and the
      support of the school, the family, sport, mass-media, judicial and medical
      infrastructures, have been organised, promoted and financed. However, it is not
      always possible to assure a real safeguarding of teenagers  rights; this
      especially happens because the problem concerning the autonomous capacity of
      minors to consent (or non consent) to the medical treatment is much debated.
      However, many contradictions still persist about the effective duration of the
      pediatric age. All the same, it must be noted that the Legislator apparently
      realised that not only the physical, psychological and social maturity proceed by
      steps, but also the legal capacity.

PMID- 11309544
TI  - [Legal regulations to protect under-aged donors issued by E.U. Member Countries.
      Analysis of the present situation and proposals].
AB  - Allogeneic bone marrow transplantation in the E.U. is a routine treatment which
      requires specific legal procedures to protect under-aged donors. The European
      Council (5/29/1978) decreed the guidelines concerning organ transplantation for
      the Member Countries. These guidelines included obtaining written consent from
      the donor or his/her guardian. The International Convention on children s rights
      (New York 11/20/1989, art. 12) stated that the minor has the right to give
      his/her opinion, which must be taken into consideration. Currently, though legal
      guidelines vary among Member Countries, all require the parents  or guardian s
      written consent. In France, an ethics committee (L. 76-1181/1976) must inform the
      minor about the consequences of the procedure, respect his/her will and obtain
      consent. In Luxembourg, the Department of Health requires written consent as well
      as authorization by three experts, including two physicians. In Spain an ethics
      committee must obtain the minor s consent which is then approved by a government
      authority and counter-signed by a physician. In UK an N.H.S. directive (1st Aug.
      1993) states that as of 16 years of age donors must give consent. In Germany
      minors over 14 are allowed to give consent. A legal guarantee is required when
      the recipient is a parent to avoid conflict of interest. In Belgium minors
      between 15 and 18 require witnessed written consent, counter-signed by the
      guardian and approved by a physician. Married donors below 21 need the consenting
      adult s approval. In Portugal verbal consent by the minor and the guardian is
      sufficient. In Denmark the guardian s written consent is needed. In Italy a law
      is being prepared to best protect minors. In conclusion it would be useful for
      the European Council to decree the detailed legal guidelines and require greater
      uniformity among the E.U. Countries.

PMID- 11309545
TI  - [Skin diseases].

PMID- 11309546
TI  - Counterfeit and substandard drugs.

PMID- 11309547
TI  - Effects of fluconazole and fluvoxamine on the pharmacokinetics and
      pharmacodynamics of glimepiride.
AB  - OBJECTIVE: Our objective was to study the effects of fluconazole and fluvoxamine
      on the pharmacokinetics and pharmacodynamics of glimepiride, a new sulfonylurea
      antidiabetic drug. METHODS: In this randomized, double-blind, three-phase
      crossover study, 12 healthy volunteers took 200 mg of fluconazole once daily (400
      mg on day 1), 100 mg of fluvoxamine once daily, or placebo once daily for 4 days.
      On day 4, a single oral dose of 0.5 mg of glimepiride was administered. Plasma
      glimepiride and blood glucose concentrations were measured up to 12 hours.
      RESULTS: In the fluconazole phase, the mean total area under the plasma
      concentration-time curve of glimepiride was 238% (P <.0001) and the peak plasma
      concentration was 151% (P <.0001) of the respective control value. The mean
      elimination half-life of glimepiride was prolonged from 2.0 to 3.3 hours (P
      <.0001) by fluconazole. In the fluvoxamine phase, the mean area under the plasma
      concentration-time curve of glimepiride was not significantly different from that
      in the placebo phase. However, the mean peak plasma concentration of glimepiride
      was 143% (P <.05) of the control and the elimination half-life was prolonged from
      2.0 to 2.3 hours (P <.01) by fluvoxamine. Fluconazole and fluvoxamine did not
      cause statistically significant changes in the effects of glimepiride on blood
      glucose concentrations. CONCLUSIONS: Fluconazole considerably increased the area
      under the plasma concentration-time curve of glimepiride and prolonged its
      elimination half-life. This was probably caused by inhibition of the cytochrome P
      450 2C9-mediated biotransformation of glimepiride by fluconazole. Concomitant use
      of fluconazole with glimepiride may increase the risk of hypoglycemia as much as
      would a 2- to 3-fold increase in the dose of glimepiride. Fluvoxamine moderately
      increased the plasma concentrations and slightly prolonged the elimination half
      life of glimepiride.

PMID- 11309548
TI  - A population pharmacokinetic screen to identify demographic-clinical covariates
      of basiliximab in liver transplantation.
AB  - BACKGROUND: Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric
      monoclonal antibody used for immunoprophylaxis in organ transplantation. It was
      assessed in a randomized, double-blind, placebo-controlled efficacy trial in de
      novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days
      0 and 4) in addition to baseline immunosuppression with cyclosporine (INN,
      ciclosporin) microemulsion and corticosteroids. METHODS: Serial blood samples
      (8.3 +/- 1.4 per patient) were collected during 12 weeks after transplantation
      from 184 basiliximab-treated patients, and empirical Bayes estimates of each
      patient's disposition parameters were derived. Demographic-clinical covariates
      were explored with regression methods. RESULTS: Basiliximab clearance was 55 +/-
      26 mL/h, the distribution volume was 9.7 +/- 4.2 L, and the half-life was 8.7 +/-
      6.7 days. Patient weight, age, sex, ethnicity, history of alcoholism, hepatitis C
      seropositivity, and notable postoperative bleeding had no clinically relevant
      influences on basiliximab disposition; however, the cumulative volume of drained
      ascites fluid in the first week was positively correlated with clearance.
      Receptor-saturating basiliximab concentrations (> or =0.1 microg/mL) were
      maintained for 38 +/- 16 days, and this was negatively correlated with the
      cumulative volume of drained ascites fluid in week 1. Patients who experienced an
      acute rejection episode did not clear basiliximab at a faster rate than their
      rejection-free peers nor did they maintain CD25-saturating concentrations for a
      shorter period. CONCLUSIONS: Although the standard dose regimen of 20 mg of
      basiliximab on days 0 and 4 after transplantation appears to be appropriate for
      the majority of patients with liver transplants, a supplemental dose at the end
      of the first week may be considered for those with substantial (>10 L)
      postoperative ascites fluid drainage.

PMID- 11309549
TI  - A population pharmacokinetic-pharmacodynamic and logistic regression analysis of
      lotrafiban in patients.
AB  - OBJECTIVE: Our objective was to assess the safety, tolerability,
      pharmacokinetics, and pharmacodynamics of lotrafiban, an oral glycoprotein
      IIb/IIIa inhibitor, in patients with a recent myocardial infarction, unstable
      angina, transient ischemic attack, or stroke. METHODS: A 12-week, double-blind,
      multi-center, placebo-controlled, parallel-group, phase II study of lotrafiban
      (the Anti-platelet Useful Dose Study) was conducted in patients. Lotrafiban or
      placebo was administered as a twice daily oral dose at four dose levels (5-100
      mg) for 12 weeks with daily doses of aspirin (300-325 mg). The pharmacokinetics
      of lotrafiban were characterized with the use of a population approach and were
      described by a two-compartment model with first order absorption and first order
      elimination. The pharmacodynamic data, ex vivo platelet aggregation, were
      described with the use of a direct effect inhibitory sigmoidal model with a
      baseline. The relationship between the severity of bleeding episodes and
      predicted steady-state lotrafiban exposure was characterized by logistic
      regression. RESULTS: Pharmacokinetic analysis showed that increasing age and
      decreasing creatinine clearance resulted in increased exposure to lotrafiban. The
      concentration-effect relationship was steep, with near complete inhibition of
      platelet aggregation at lotrafiban concentrations in excess of 20 ng/mL. Logistic
      regression showed that at exposures that exceeded approximately 835 ng. h/mL, the
      severity of adverse bleeding events increased considerably; this suggested that
      dosing recommendations should be generated to minimize the likelihood of patients
      having an area under the plasma concentration-time curve from 0 to 24 hours in
      excess of this value. CONCLUSIONS: Patients whose age exceeded 65 years or whose
      creatinine clearance was less than 60 mL/min should be given a lower dose of
      lotrafiban than younger patients with good renal function.

PMID- 11309551
TI  - Furosemide-probenecid interaction as a laboratory exercise for undergraduate
      education in clinical pharmacology.
AB  - OBJECTIVE: The aim of this study was to determine the easiness, reproducibility,
      and safety of a laboratory exercise for a drug interaction between furosemide and
      probenecid. METHODS: From 1995 to 1999 approximately 100 medical students
      participated in the exercise each year after they gave written informed consent.
      The students were randomly assigned to one of the three groups in a double-blind
      fashion: group 1, placebo plus 20 mg of furosemide; group 2, 250 mg of probenecid
      plus 20 mg of furosemide; and group 3, 1000 mg of probenecid plus 20 mg of
      furosemide. The students took probenecid or its placebo 1 hour before furosemide.
      Urine volume and urinary sodium excretion were measured for 3 hours after
      furosemide. At the end of the exercise in 1999, students responded to several
      questionnaires concerning the utility of furosemide. RESULTS: The entire course
      of the exercise was completed within half a day. The following findings were
      obtained every year. (1) Probenecid dose dependently blunted the diuretic effects
      of furosemide. (2) Time courses of the diuretic effects were altered by
      probenecid. Ten to twenty percent of the students had slight complaints but
      completed the exercise without any medications. Finally, more than 80% of the
      students considered the exercise to be useful. CONCLUSIONS: The data suggest that
      the exercise of the drug interaction between furosemide and probenecid is easy to
      perform, reproducible, and safe. Through the experience of the laboratory
      exercise, students will develop an attitude to assess and estimate potential drug
      interactions before they prescribe drugs.

PMID- 11309550
TI  - The endothelin antagonist bosentan inhibits the canalicular bile salt export
      pump: a potential mechanism for hepatic adverse reactions.
AB  - BACKGROUND: During clinical trials bosentan, the first orally active endothelin
      receptor antagonist, caused asymptomatic transaminase elevations in some
      patients. In this study we investigated whether inhibition of the
      hepatocanalicular bile salt export pump (rodents, Bsep; humans, BSEP ABCB11)
      could account for bosentan-induced liver injury. METHODS: We reanalyzed the
      safety database of the bosentan trials for cholestatic liver injury, determined
      the cholestatic potency of bosentan in the rat, and studied the effects of
      bosentan and its metabolites on Bsep-mediated taurocholate transport in vitro.
      RESULTS: Bosentan caused dose-dependent and reversible liver injury in 2% to 18%
      of patients and caused a significant increase of serum bile salt levels (P <.01).
      Concomitant administration of glyburide (INN, glibenclamide) enhanced the
      cholestatic potency of bosentan. Similar effects were seen in rats, in which
      serum bile salt levels were increased by glyburide less than by bosentan, which
      increased the levels less than a combination of bosentan and glyburide. In vitro,
      Bsep-mediated taurocholate transport was inhibited by bosentan (inhibition
      constant, approximately 12 micromol/L) and metabolites (inhibition constant,
      approximately 8.5 micromol/L for metabolite Ro 47-8634). CONCLUSIONS: These
      results indicate that bosentan-induced liver injury is mediated, at least in
      part, by inhibition of Bsep/BSEP-causing intracellular accumulation of cytotoxic
      bile salts and bile salt induced liver cell damage. The data further emphasize
      the pathophysiologic importance of drug-Bsep interactions in acquired forms of
      cholestatic liver injury.

PMID- 11309552
TI  - Beta-blockade with nebivolol enhances the acetylcholine-induced cutaneous
      vasodilation.
AB  - Nebivolol is a selective beta(1)-adrenoceptor blocker that has a vasorelaxant
      activity thought to be the result of a facilitation of the release of nitric
      oxide from the endothelium. This study was undertaken in 12 healthy male
      volunteers to assess whether this compound increases the vasodilatory response to
      acetylcholine when administered orally at a dose commonly recommended for the
      treatment of cardiovascular diseases. The subjects were randomly allocated to an
      8-day treatment with nebivolol (5 mg once a day) and atenolol (50 mg once a day)
      according to a cross-over design. The two treatments were separated by a 1-week
      washout period. On the first and the last day of each treatment phase, both
      before drug administration and 3 hours after drug administration, the forearm
      skin blood flow response to acetylcholine applied by iontophoresis was determined
      with the use of a laser Doppler scanner imaging system. The reactivity to
      acetylcholine was significantly increased 3 hours after the administration of
      nebivolol on both the first and the last day of treatment, whereas atenolol had
      no effect on this parameter. These data therefore indicate that nebivolol, but
      not atenolol, enhances the vasorelaxant activity of acetylcholine in the skin
      vascular bed; this is compatible with a facilitation by this beta-blocker of the
      endothelium-dependent vasodilation.

PMID- 11309553
TI  - Specific effect of venlafaxine on single and repetitive experimental painful
      stimuli in humans.
AB  - BACKGROUND: Tricyclic antidepressants relieve neuropathic pain, and the analgesic
      properties of tricyclic antidepressants are substantiated in human experimental
      pain models. It has been speculated that drugs with a selective inhibition of
      presynaptic reuptake of both serotonin and noradrenaline could have an analgesic
      effect comparable to the analgesic effect of tricyclic antidepressants.
      OBJECTIVE: Our objective was to evaluate the analgesic effect of the serotonin
      noradrenaline reuptake inhibitor venlafaxine in human experimental pain models.
      METHOD: The study was carried out as a randomized, placebo-controlled, double
      blind, crossover experiment that included 16 healthy volunteers. A 37.5-mg dose
      of venlafaxine was given orally 4 times with 12-hour intervals, and pain tests
      were performed before and 3 hours after the second and fourth doses. Pain tests
      included the determination of pain detection and tolerance thresholds to
      pressure, pain detection and tolerance thresholds on single electrical
      transcutaneous stimulation of the sural nerve, pain temporal summation on
      repetitive electrical sural nerve stimulation, and pain experienced during the
      cold pressor test. RESULTS: Venlafaxine increased thresholds for pain tolerance
      after single electrical stimulation (P =.005) and pain summation (P =.01) on
      repetitive stimulation but did not alter the thresholds for pain detection after
      single electrical sural nerve stimulation. Venlafaxine did not alter pain
      experienced during the cold pressor test or increase the pressure pain
      thresholds. CONCLUSION: Venlafaxine increases the pain tolerance threshold to
      electrical sural nerve stimulation and the threshold at which pain increases
      (pain summation). The impact of venlafaxine on pain summation in this
      experimental pain model on repetitive stimulation may indicate a potential
      analgesic effect for clinical neuropathic pain.

PMID- 11309554
TI  - Gastrin-releasing peptide is a potent vasodilator in humans.
AB  - OBJECTIVES: Our objective was to characterize the local vascular effects of
      gastrin-releasing peptide in forearm resistance vessels as a biomarker to aid the
      clinical development of broad-spectrum neuropeptide antagonists as anticancer
      agents. METHODS: On different occasions, 7 healthy male volunteers received
      brachial artery infusions of gastrin-releasing peptide, and forearm blood flow
      was measured by venous occlusion plethysmography. Dose-finding studies identified
      a range of pharmacologically active doses of gastrin-releasing peptide (3 to 450
      pmol/min) for use in dose response and tachyphylaxis studies. The nitric oxide
      clamp method was used for the assessment of the contribution of nitric oxide to
      the vasodilatory effect shown. RESULTS AND CONCLUSIONS: Gastrin-releasing peptide
      proved to be a potent, dose-dependent arteriolar vasodilator. The time to onset
      and offset of effect was rapid, within minutes, and marked tachyphylaxis was
      shown, with recovery by approximately 20 minutes. The contribution of nitric
      oxide to this vasodilatation was minimal. Forearm blood flow studies with the use
      of gastrin-releasing peptide may be usefully incorporated into the further
      clinical development of broad-spectrum neuropeptide growth factor antagonists.

PMID- 11309555
TI  - Preventing drug interactions by online prescription screening in community
      pharmacies and medical practices.
AB  - BACKGROUND: Drug interactions have been shown to be preventable by computerized
      prescription entry and screening only in hospitals and not in community-based
      practice. METHODS: We retrospectively evaluated the effect of online prescription
      screening in community pharmacies and physician offices of one health maintenance
      organization, phased in during 3 consecutive 6-month periods in 1998 to 1999
      (period I, system active only in 40% of pharmacies; period II, system active in
      90% of pharmacies and 50% of physician offices; period III, system active in 95%
      of pharmacies and 90% of physician practices), on rates of prescriptions with-,
      patient exposure to-, and physician prescribing of-potential drug interactions.
      FINDINGS: Cumulative data included 775,186 patients given at least one
      prescription, by one or more of 5504 physicians, whose prescriptions were
      dispensed at 572 pharmacies. Dispensing of drug interaction prescriptions was
      reduced by 21.1% and by 67.5% in periods II and III compared with period I (odds
      ratio, 0.79; 95% confidence limit, 0.75-0.83 and odds ratio, 0.28; 95% confidence
      limit, 0.26-0.30, respectively). Patient exposure decreased only in those
      receiving 3 to 7 concurrent drugs (odds ratio, 0.80; 95% confidence limit, 0.71
      0.90) with no reductions for patients who were given 2 drugs or 8 or more drugs.
      Only 19% to 25% of physicians wrote prescriptions for drugs that interact, but
      85% of these repeated this pattern after being alerted. The proportion of
      prescriptions of drugs that interact that originated with a single prescriber, as
      opposed to 2 prescribers, decreased during the 3 periods from 0.81 to 0.74 and
      0.69 (P <.001). INTERPRETATION: Computerized prescription entry and drug
      interaction screening in the community caused a 62.8% reduction in pharmacy
      dispensed prescriptions with severe drug interactions and a 20% reduction in
      patient exposure to prescriptions with severe drug interactions; this reduction
      was negated by polypharmacy of 8 or more drugs. The effect of interaction alerts
      on physician prescribing patterns was limited.

PMID- 11309556
TI  - Effect of omeprazole on the pharmacokinetics of moclobemide according to the
      genetic polymorphism of CYP2C19.
AB  - BACKGROUND: Moclobemide, an antidepressant with selective monoamine oxidase-A
      inhibitory action, is known to be metabolized by CYP2C19 and is also reported to
      be an inhibitor of CYP2C19, CYP2D6, and CYP1A2. To confirm the involvement of
      CYP2C19, we performed a pharmacokinetic interaction study. METHODS: The effect of
      omeprazole on the pharmacokinetics of moclobemide was studied in 16 healthy
      volunteers. The volunteer group comprised 8 extensive metabolizers and 8 poor
      metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were
      randomly allocated into two sequence groups, and a single-blind, placebo
      controlled, two-period crossover study was performed. In study I, a placebo was
      orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and
      40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic
      study was performed. During study II, 40 mg of omeprazole was given each morning
      instead of placebo, and pharmacokinetic studies were performed on the first and
      eighth day with 300 mg of moclobemide coadministration. RESULTS: The inhibition
      of moclobemide metabolism was significant in extensive metabolizers even after a
      single dose of omeprazole. After daily administration of omeprazole for 1 week,
      the pharmacokinetic parameters of moclobemide and its metabolites in extensive
      metabolizers changed to values similar to those in poor metabolizers. In poor
      metabolizers, no remarkable changes in the pharmacokinetic parameters were
      observed. CONCLUSION: Our results show that CYP2C19 is an important enzyme in the
      elimination of moclobemide and that it is extensively inhibited by omeprazole in
      extensive metabolizers, but not in poor metabolizers.

PMID- 11309557
TI  - Revolution and reform or immutability and invariability.

PMID- 11309558
TI  - It's time to require theory and methods of quality improvement in basic and
      graduate nursing education.

PMID- 11309559
TI  - Spiral dynamics: Leadership insights.

PMID- 11309560
TI  - Professionalism revisited.

PMID- 11309561
TI  - Follow-up conversation with Lucian Leape on errors and adverse events in health
      care. Interview by Peter I. Buerhaus.

PMID- 11309562
TI  - Nurse staffing and adverse patient outcomes: a systems approach.

PMID- 11309563
TI  - Evolution of the mid range theory of comfort for outcomes research.

PMID- 11309564
TI  - Patient outcomes: a matter of perspective.

PMID- 11309565
TI  - Telehealth advancing nursing practice.

PMID- 11309566
TI  - President's message. Nursing workforce concerns: getting to the greater policy
      issues.

PMID- 11309567
TI  - Free and public expression.

PMID- 11309568
TI  - Science without a tinge of green.

PMID- 11309570
TI  - Astronomers concerned by plan to give NASA ground control.

PMID- 11309572
TI  - Earth sciences and biodiversity fall victim to budget plan.

PMID- 11309574
TI  - Cancer comes under scrutiny in fresh genomics initiative.

PMID- 11309576
TI  - Japan prepares to pitch for international fusion reactor.

PMID- 11309575
TI  - Blood product from cattle wins approval for use in humans.

PMID- 11309578
TI  - Satellite will probe mutating seeds in space.

PMID- 11309579
TI  - Animal labs fearful over activists' plan to name names.

PMID- 11309581
TI  - When the chips are down.

PMID- 11309582
TI  - The story of O.

PMID- 11309583
TI  - Biotech offers Africans a chance to create their own practical solutions.

PMID- 11309584
TI  - Kansas science saved by teachers' good sense.

PMID- 11309585
TI  - Bright light of learning snuffed out in Breslau.

PMID- 11309586
TI  - New information on the biodiversity facility.

PMID- 11309587
TI  - A year of opportunity.

PMID- 11309594
TI  - Strings and things.

PMID- 11309595
TI  - A tool, not a tyrant.

PMID- 11309596
TI  - The promise of protonics.

PMID- 11309597
TI  - Molecular motors. Doing a rotary two-step.

PMID- 11309598
TI  - Fundamental physics. Newton rules (for now).

PMID- 11309601
TI  - Materials science. Polymers all in a row.

PMID- 11309599
TI  - Cell biology. Proteolytic relay comes to an end.

PMID- 11309602
TI  - Vision. Why do colours fade at the edges?

PMID- 11309605
TI  - Subsidence risk from thawing permafrost.

PMID- 11309606
TI  - Neuroperception. Early visual experience and face processing.

PMID- 11309607
TI  - Increased sedimentation rates and grain sizes 2-4 Myr ago due to the influence of
      climate change on erosion rates.
AB  - Around the globe, and in a variety of settings including active and inactive
      mountain belts, increases in sedimentation rates as well as in grain sizes of
      sediments were recorded at approximately 2-4 Myr ago, implying increased erosion
      rates. A change in climate represents the only process that is globally
      synchronous and can potentially account for the widespread increase in erosion
      and sedimentation, but no single process-like a lowering of sea levels or
      expanded glaciation-can explain increases in sedimentation in all environments,
      encompassing continental margins and interiors, and tropical as well as higher
      latitudes. We suggest that climate affected erosion mainly by the transition from
      a period of climate stability, in which landscapes had attained equilibrium
      configurations, to a time of frequent and abrupt changes in temperature,
      precipitation and vegetation, which prevented fluvial and glacial systems from
      establishing equilibrium states.

PMID- 11309608
TI  - Resolution of distinct rotational substeps by submillisecond kinetic analysis of
      F1-ATPase.
AB  - The enzyme F1-ATPase has been shown to be a rotary motor in which the central
      gamma-subunit rotates inside the cylinder made of alpha3beta3 subunits. At low
      ATP concentrations, the motor rotates in discrete 120 degrees steps, consistent
      with sequential ATP hydrolysis on the three beta-subunits. The mechanism of
      stepping is unknown. Here we show by high-speed imaging that the 120 degrees step
      consists of roughly 90 degrees and 30 degrees substeps, each taking only a
      fraction of a millisecond. ATP binding drives the 90 degrees substep, and the 30
      degrees substep is probably driven by release of a hydrolysis product. The two
      substeps are separated by two reactions of about 1 ms, which together occupy most
      of the ATP hydrolysis cycle. This scheme probably applies to rotation at full
      speed ( approximately 130 revolutions per second at saturating ATP) down to
      occasional stepping at nanomolar ATP concentrations, and supports the binding
      change model for ATP synthesis by reverse rotation of F1-ATPase.

PMID- 11309609
TI  - Efficient mixing at low Reynolds numbers using polymer additives.
AB  - Mixing in fluids is a rapidly developing area in fluid mechanics, being an
      important industrial and environmental problem. The mixing of liquids at low
      Reynolds numbers is usually quite weak in simple flows, and it requires special
      devices to be efficient. Recently, the problem of mixing was solved analytically
      for a simple case of random flow, known as the Batchelor regime. Here we
      demonstrate experimentally that very viscous liquids containing a small amount of
      high-molecular-weight polymers can be mixed quite efficiently at very low
      Reynolds numbers, for a simple flow in a curved channel. A polymer concentration
      of only 0.001% suffices. The presence of the polymers leads to an elastic
      instability and to irregular flow, with velocity spectra corresponding to the
      Batchelor regime. Our detailed observations of the mixing in this regime enable
      us to confirm several important theoretical predictions: the probability
      distributions of the concentration exhibit exponential tails, moments of the
      distribution decay exponentially along the flow, and the spatial correlation
      function of concentration decays logarithmically.

PMID- 11309610
TI  - Magnetic-field-induced superconductivity in a two-dimensional organic conductor.
AB  - The application of a sufficiently strong magnetic field to a superconductor will,
      in general, destroy the superconducting state. Two mechanisms are responsible for
      this. The first is the Zeeman effect, which breaks apart the paired electrons if
      they are in a spin-singlet (but not a spin-triplet) state. The second is the so
      called 'orbital' effect, whereby the vortices penetrate into the superconductors
      and the energy gain due to the formation of the paired electrons is lost. For the
      case of layered, two-dimensional superconductors, such as the high-Tc copper
      oxides, the orbital effect is reduced when the applied magnetic field is parallel
      to the conducting layers. Here we report resistance and magnetic-torque
      experiments on single crystals of the quasi-two-dimensional organic conductor
      lambda-(BETS)2FeCl4, where BETS is bis(ethylenedithio)tetraselenafulvalene. We
      find that for magnetic fields applied exactly parallel to the conducting layers
      of the crystals, superconductivity is induced for fields above 17 T at a
      temperature of 0.1 K. The resulting phase diagram indicates that the transition
      temperature increases with magnetic field, that is, the superconducting state is
      further stabilized with magnetic field.

PMID- 11309611
TI  - Solid acids as fuel cell electrolytes.
AB  - Fuel cells are attractive alternatives to combustion engines for electrical power
      generation because of their very high efficiencies and low pollution levels.
      Polymer electrolyte membrane fuel cells are generally considered to be the most
      viable approach for mobile applications. However, these membranes require humid
      operating conditions, which limit the temperature of operation to less than 100
      degrees C; they are also permeable to methanol and hydrogen, which lowers fuel
      efficiency. Solid, inorganic, acid compounds (or simply, solid acids) such as
      CsHSO4 and Rb3H(SeO4)2 have been widely studied because of their high proton
      conductivities and phase-transition behaviour. For fuel-cell applications they
      offer the advantages of anhydrous proton transport and high-temperature stability
      (up to 250 degrees C). Until now, however, solid acids have not been considered
      viable fuel-cell electrolyte alternatives owing to their solubility in water and
      extreme ductility at raised temperatures (above approximately 125 degrees C).
      Here we show that a cell made of a CsHSO4 electrolyte membrane (about 1.5 mm
      thick) operating at 150-160 degrees C in a H2/O2 configuration exhibits promising
      electrochemical performances: open circuit voltages of 1.11 V and current
      densities of 44 mA cm-2 at short circuit. Moreover, the solid-acid properties
      were not affected by exposure to humid atmospheres. Although these initial
      results show promise for applications, the use of solid acids in fuel cells will
      require the development of fabrication techniques to reduce electrolyte
      thickness, and an assessment of possible sulphur reduction following prolonged
      exposure to hydrogen.

PMID- 11309612
TI  - Self-assembly of mesoscopically ordered chromatic polydiacetylene/silica
      nanocomposites.
AB  - Nature abounds with intricate composite architectures composed of hard and soft
      materials synergistically intertwined to provide both useful functionality and
      mechanical integrity. Recent synthetic efforts to mimic such natural designs have
      focused on nanocomposites, prepared mainly by slow procedures like monomer or
      polymer infiltration of inorganic nanostructures or sequential deposition. Here
      we report the self-assembly of conjugated polymer/silica nanocomposite films with
      hexagonal, cubic or lamellar mesoscopic order using polymerizable amphiphilic
      diacetylene molecules as both structure-directing agents and monomers. The self
      assembly procedure is rapid and incorporates the organic monomers uniformly
      within a highly ordered, inorganic environment. Polymerization results in
      polydiacetylene/silica nanocomposites that are optically transparent and
      mechanically robust. Compared to ordered diacetylene-containing films prepared as
      Langmuir monolayers or by Langmuir-Blodgett deposition, the nanostructured
      inorganic host alters the diacetylene polymerization behaviour, and the resulting
      nanocomposite exhibits unusual chromatic changes in response to thermal,
      mechanical and chemical stimuli. The inorganic framework serves to protect,
      stabilize, and orient the polymer, and to mediate its function. The nanocomposite
      architecture also provides sufficient mechanical integrity to enable integration
      into devices and microsystems.

PMID- 11309613
TI  - Early Oligocene initiation of North Atlantic Deep Water formation.
AB  - Dating the onset of deep-water flow between the Arctic and North Atlantic oceans
      is critical for modelling climate change in the Northern Hemisphere and for
      explaining changes in global ocean circulation throughout the Cenozoic era (from
      about 65 million years ago to the present). In the early Cenozoic era, exchange
      between these two ocean basins was inhibited by the Greenland-Scotland ridge, but
      a gateway through the Faeroe-Shetland basin has been hypothesized. Previous
      estimates of the date marking the onset of deep-water circulation through this
      basin-on the basis of circumstantial evidence from neighbouring basins-have been
      contradictory, ranging from about 35 to 15 million years ago. Here we describe
      the newly discovered Southeast Faeroes drift, which extends for 120 km parallel
      to the basin axis. The onset of deposition in this drift has been dated to the
      early Oligocene epoch ( approximately 35 million years ago) from a petroleum
      exploration borehole. We show that the drift was deposited under a southerly flow
      regime, and conclude that the initiation of deep-water circulation from the
      Norwegian Sea into the North Atlantic Ocean took place much earlier than is
      currently assumed in most numerical models of ancient ocean circulation.

PMID- 11309614
TI  - Melt retention and segregation beneath mid-ocean ridges.
AB  - Geochemical models of melting at mid-ocean ridges-particularly those based on
      trace elements and uranium-decay-series isotopes-predict that melt segregates
      from the matrix at very low porosities, of order 0.1%. Some of these models also
      require that the melt ascends rapidly. But these predictions appear to conflict
      with seismic data obtained by the mantle electromagnetic and tomography (MELT)
      experiment. These data reveal, beneath the East Pacific Rise (at 17 degrees S), a
      region of low velocities several hundred kilometres wide, which is best explained
      by the presence of 1-2% melt, distributed on a grain scale in disk-shaped
      geometries. Here I show that these apparently contradictory constraints can be
      reconciled by taking into account the geometry and resulting permeability of the
      intergranular network of melt, together with the changing character of the melt
      as it ascends. A deep, volatile-rich melt with low viscosity and density is
      mobile at 0.1% porosity, but basaltic melt only becomes mobile at a porosity
      above 1%. While the volumetric contribution of the volatile-rich melt to the
      erupted basalts is small, the isotopic disequilibria (except for radium)
      generated by porous flow of this melt are preserved if melt transport is rapid at
      the onset of high-productivity melting. Also, because of incomplete extraction,
      some melt is retained in a broad zone, consistent with the MELT observations.

PMID- 11309615
TI  - Towards a general theory of biodiversity.
AB  - The study of patterns in living diversity is driven by the desire to find the
      universal rules that underlie the organization of ecosystems. The relative
      abundance distribution, which characterizes the total number and abundance of
      species in a community, is arguably the most fundamental measure in ecology.
      Considerable effort has been expended in striving for a general theory that can
      explain the form of the distribution. Despite this, a mechanistic understanding
      of the form in terms of physiological and environmental parameters remains
      elusive. Recently, it has been proposed that space plays a central role in
      generating the patterns of diversity. Here we show that an understanding of the
      observed form of the relative abundance distribution requires a consideration of
      how individuals pack in time. We present a framework for studying the dynamics of
      communities which generalizes the prevailing species-based approach to one based
      on individuals that are characterized by their physiological traits. The observed
      form of the abundance distribution and its dependence on richness and disturbance
      are reproduced, and can be understood in terms of the trade-off between time to
      reproduction and fecundity.

PMID- 11309616
TI  - Sustainability of three apple production systems.
AB  - Escalating production costs, heavy reliance on non-renewable resources, reduced
      biodiversity, water contamination, chemical residues in food, soil degradation
      and health risks to farm workers handling pesticides all bring into question the
      sustainability of conventional farming systems. It has been claimed, however,
      that organic farming systems are less efficient, pose greater health risks and
      produce half the yields of conventional farming systems. Nevertheless, organic
      farming became one of the fastest growing segments of US and European agriculture
      during the 1990s. Integrated farming, using a combination of organic and
      conventional techniques, has been successfully adopted on a wide scale in Europe.
      Here we report the sustainability of organic, conventional and integrated apple
      production systems in Washington State from 1994 to 1999. All three systems gave
      similar apple yields. The organic and integrated systems had higher soil quality
      and potentially lower negative environmental impact than the conventional system.
      When compared with the conventional and integrated systems, the organic system
      produced sweeter and less tart apples, higher profitability and greater energy
      efficiency. Our data indicate that the organic system ranked first in
      environmental and economic sustainability, the integrated system second and the
      conventional system last.

PMID- 11309617
TI  - The concepts of 'sameness' and 'difference' in an insect.
AB  - Insects process and learn information flexibly to adapt to their environment. The
      honeybee Apis mellifera constitutes a traditional model for studying learning and
      memory at behavioural, cellular and molecular levels. Earlier studies focused on
      elementary associative and non-associative forms of learning determined by either
      olfactory conditioning of the proboscis extension reflex or the learning of
      visual stimuli in an operant context. However, research has indicated that bees
      are capable of cognitive performances that were thought to occur only in some
      vertebrate species. For example, honeybees can interpolate visual information,
      exhibit associative recall, categorize visual information and learn contextual
      information. Here we show that honeybees can form 'sameness' and 'difference'
      concepts. They learn to solve 'delayed matching-to-sample' tasks, in which they
      are required to respond to a matching stimulus, and 'delayed non-matching-to
      sample' tasks, in which they are required to respond to a different stimulus;
      they can also transfer the learned rules to new stimuli of the same or a
      different sensory modality. Thus, not only can bees learn specific objects and
      their physical parameters, but they can also master abstract inter-relationships,
      such as sameness and difference.

PMID- 11309618
TI  - Chromatic sensitivity of ganglion cells in the peripheral primate retina.
AB  - Visual abilities change over the visual field. For example, our ability to detect
      movement is better in peripheral vision than in foveal vision, but colour
      discrimination is markedly worse. The deterioration of colour vision has been
      attributed to reduced colour specificity in cells of the midget, parvocellular
      (PC) visual pathway in the peripheral retina. We have measured the colour
      specificity (red-green chromatic modulation sensitivity) of PC cells at
      eccentricities between 20 and 50 degrees in the macaque retina. Here we show that
      most peripheral PC cells have red-green modulation sensitivity close to that of
      foveal PC cells. This result is incompatible with the view that PC pathway cells
      in peripheral retina make indiscriminate connections ('random wiring') with
      retinal circuits devoted to different spectral types of cone photoreceptors. We
      show that selective cone connections can be maintained by dendritic field
      anisotropy, consistent with the morphology of PC cell dendritic fields in
      peripheral retina. Our results also imply that postretinal mechanisms contribute
      to the psychophysically demonstrated deterioration of colour discrimination in
      the peripheral visual field.

PMID- 11309619
TI  - A CaMK IV responsive RNA element mediates depolarization-induced alternative
      splicing of ion channels.
AB  - Calcium regulation of gene expression is critical for the long-lasting activity
      dependent changes in cellular electrical properties that underlie important
      physiological functions such as learning and memory. Cellular electrical
      properties are diversified through the extensive alternative splicing of ion
      channel pre-messenger RNAs; however, the regulation of splicing by cell
      signalling pathways has not been well explored. Here we show that depolarization
      of GH3 pituitary cells represses splicing of the STREX exon in BK potassium
      channel transcripts through the action of Ca2+/calmodulin-dependent protein
      kinases (CaMKs). Overexpressing constitutively active CaMK IV, but not CaMK I or
      II, specifically decreases STREX inclusion in the mRNA. This decrease is
      prevented by mutations in particular RNA repressor sequences. Transferring 54
      nucleotides from the 3' splice site upstream of STREX to a heterologous gene is
      sufficient to confer CaMK IV repression on an otherwise constitutive exon. These
      experiments define a CaMK IV-responsive RNA element (CaRRE), which mediates the
      alternative splicing of ion channel pre-mRNAs. The CaRRE presents a unique
      molecular target for inducing long-term adaptive changes in cellular electrical
      properties. It also provides a model system for dissecting the effect of signal
      transduction pathways on alternative splicing.

PMID- 11309620
TI  - Neuropeptide Y functions as a neuroproliferative factor.
AB  - Neuropeptide Y (NPY) has a number of functions in mammalian physiology. Here we
      identify a role for NPY in promoting proliferation of postnatal neuronal
      precursor cells. NPY is synthesized in the postnatal olfactory epithelium by
      sustentacular cells, previously proposed to function only in structural support.
      Mice with a targeted deletion of NPY contain half as many dividing olfactory
      neuronal precursor cells as do controls. Furthermore, NPY-deficient mice develop
      significantly fewer olfactory neurons by adulthood. NPY acts on multipotent
      neuronal precursor or basal cells to activate rapidly and transiently the
      extracellular signal-regulated kinase (ERK)1/2 subgroup of mitogen-activated
      protein kinases. The NPY Y1 receptor subtype appears to mediate this effect. The
      ability of NPY to induce neuronal precursor proliferation is mediated by protein
      kinase C (PKC), indicating an upstream PKC-dependent activation of ERK1/2. These
      results indicate that NPY may regulate neuronal precursor proliferation in the
      adult mammal.

PMID- 11309621
TI  - Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of
      TC10.
AB  - The stimulation of glucose uptake by insulin in muscle and adipose tissue
      requires translocation of the GLUT4 glucose transporter protein from
      intracellular storage sites to the cell surface. Although the cellular dynamics
      of GLUT4 vesicle trafficking are well described, the signalling pathways that
      link the insulin receptor to GLUT4 translocation remain poorly understood.
      Activation of phosphatidylinositol-3-OH kinase (PI(3)K) is required for this
      trafficking event, but it is not sufficient to produce GLUT4 translocation. We
      previously described a pathway involving the insulin-stimulated tyrosine
      phosphorylation of Cbl, which is recruited to the insulin receptor by the adapter
      protein CAP. On phosphorylation, Cbl is translocated to lipid rafts. Blocking
      this step completely inhibits the stimulation of GLUT4 translocation by insulin.
      Here we show that phosphorylated Cbl recruits the CrkII-C3G complex to lipid
      rafts, where C3G specifically activates the small GTP-binding protein TC10. This
      process is independent of PI(3)K, but requires the translocation of Cbl, Crk and
      C3G to the lipid raft. The activation of TC10 is essential for insulin-stimulated
      glucose uptake and GLUT4 translocation. The TC10 pathway functions in parallel
      with PI(3)K to stimulate fully GLUT4 translocation in response to insulin.

PMID- 11309622
TI  - The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic
      factors.
AB  - Migration is a basic feature of many cell types in a wide range of species. Since
      the 1800s, cell migration has been proposed to occur in the nervous and immune
      systems, and distinct molecular cues for mammalian neurons and leukocytes have
      been identified. Here we report that Slit, a secreted protein previously known
      for its role of repulsion in axon guidance and neuronal migration, can also
      inhibit leukocyte chemotaxis induced by chemotactic factors. Slit inhibition of
      the chemokine-induced chemotaxis can be reconstituted by the co-expression of a
      chemokine receptor containing seven transmembrane domains and Roundabout (Robo),
      a Slit receptor containing a single transmembrane domain. Thus, there is a
      functional interaction between single and seven transmembrane receptors. Our
      results reveal the activity of a neuronal guidance cue in regulating leukocyte
      migration and indicate that there may be a general conservation of guidance
      mechanisms underlying metazoan cell migration. In addition, we have uncovered an
      inhibitor of leukocyte chemotaxis, and propose a new therapeutic approach to
      treat diseases involving leukocyte migration and chemotactic factors.

PMID- 11309623
TI  - Phototropin-related NPL1 controls chloroplast relocation induced by blue light.
AB  - In photosynthetic cells, chloroplasts migrate towards illuminated sites to
      optimize photosynthesis and move away from excessively illuminated areas to
      protect the photosynthetic machinery. Although this movement of chloroplasts in
      response to light has been known for over a century, the photoreceptor mediating
      this process has not been identified. The Arabidopsis gene NPL1 (ref. 2) is a
      paralogue of the NPH1 gene, which encodes phototropin, a photoreceptor for
      phototropic bending. Here we show that NPL1 is required for chloroplast
      relocation induced by blue light. A loss-of-function npl1 mutant showed no
      chloroplast avoidance response in strong blue light, whereas the accumulation of
      chloroplasts in weak light was normal. These results indicate that NPL1 may
      function as a photoreceptor mediating chloroplast relocation.

PMID- 11309624
TI  - Degradation of a cohesin subunit by the N-end rule pathway is essential for
      chromosome stability.
AB  - Cohesion between sister chromatids is established during DNA replication and
      depends on a protein complex called cohesin. At the metaphase-anaphase transition
      in the yeast Saccharomyces cerevisiae, the ESP1-encoded protease separin cleaves
      SCC1, a subunit of cohesin with a relative molecular mass of 63,000 (Mr 63K). The
      resulting 33K carboxy-terminal fragment of SCC1 bears an amino-terminal arginine
      a destabilizing residue in the N-end rule. Here we show that the SCC1 fragment is
      short-lived (t1/2 approximately 2 min), being degraded by the
      ubiquitin/proteasome-dependent N-end rule pathway. Overexpression of a long-lived
      derivative of the SCC1 fragment is lethal. In ubr1Delta cells, which lack the N
      end rule pathway, we found a highly increased frequency of chromosome loss. The
      bulk of increased chromosome loss in ubr1Delta cells is caused by metabolic
      stabilization of the ESP1-produced SCC1 fragment. This fragment is the first
      physiological substrate of the N-end rule pathway that is targeted through its N
      terminal residue. A number of yeast proteins bear putative cleavage sites for the
      ESP1 separin, suggesting other physiological substrates and functions of the N
      end rule pathway.

PMID- 11309625
TI  - Gulliver's travels in HIVland.
AB  - The emergence of HIV and AIDS is narrated here through the eyes of the legendary
      Irish traveller Gulliver, observing the replication, cross-species origin,
      evolution, diversity and transmission of HIV. Ethical problems of vaccine trials,
      the social impact of AIDS, and prospects for its prevention, including the
      development of topical virucidal lotions, are discussed. The existence of a
      growing proportion of HIV-infected, immunocompromised children and adults may
      significantly affect current immunization programmes and the evolution of
      opportunistic infections.

PMID- 11309626
TI  - The global impact of HIV/AIDS.
AB  - The scale of the human immunodeficiency virus (HIV)/AIDS epidemic has exceeded
      all expectations since its identification 20 years ago. Globally, an estimated 36
      million people are currently living with HIV, and some 20 million people have
      already died, with the worst of the epidemic centred on sub-Saharan Africa. But
      just as the spread of HIV has been greater than predicted, so too has been its
      impact on social capital, population structure and economic growth. Responding to
      AIDS on a scale commensurate with the epidemic is a global imperative, and the
      tools for an effective response are known. Nothing less than a sustained social
      mobilization is necessary to combat one of the most serious crises facing human
      development.

PMID- 11309627
TI  - The dynamics of CD4+ T-cell depletion in HIV disease.
AB  - The size and composition of the CD4+ T-cell population is regulated by balanced
      proliferation of progenitor cells and death of mature progeny. After infection
      with the human immunodeficiency virus, this homeostasis is often disturbed and
      CD4+ T cells are instead depleted. Such depletion cannot result simply from
      accelerated destruction of mature CD4+ T cells - sources of T-cell production
      must also fail. Ironically, this failure may be precipitated by physiological
      mechanisms designed to maintain homeostasis in the face of accelerated T-cell
      loss.

PMID- 11309628
TI  - Cellular immune responses to HIV.
AB  - The cellular immune response to the human immunodeficiency virus, mediated by T
      lymphocytes, seems strong but fails to control the infection completely. In most
      virus infections, T cells either eliminate the virus or suppress it indefinitely
      as a harmless, persisting infection. But the human immunodeficiency virus
      undermines this control by infecting key immune cells, thereby impairing the
      response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The
      failure of the latter to function efficiently facilitates the escape of virus
      from immune control and the collapse of the whole immune system.

PMID- 11309629
TI  - Pathways to neuronal injury and apoptosis in HIV-associated dementia.
AB  - Human immunodeficiency virus-1 (HIV-1) can induce dementia with alarming
      occurrence worldwide. The mechanism remains poorly understood, but discovery in
      brain of HIV-1-binding sites (chemokine receptors) provides new insights. HIV-1
      infects macrophages and microglia, but not neurons, although neurons are injured
      and die by apoptosis. The predominant pathway to neuronal injury is indirect
      through release of macrophage, microglial and astrocyte toxins, although direct
      injury by viral proteins might also contribute. These toxins overstimulate
      neurons, resulting in the formation of free radicals and excitotoxicity, similar
      to other neurodegenerative diseases. Recent advances in understanding the
      signalling pathways mediating these events offer hope for therapeutic
      intervention.

PMID- 11309630
TI  - HIV chemotherapy.
AB  - The use of chemotherapy to suppress replication of the human immunodeficiency
      virus (HIV) has transformed the face of AIDS in the developed world. Pronounced
      reductions in illness and death have been achieved and healthcare utilization has
      diminished. HIV therapy has also provided many new insights into the pathogenesis
      and the viral and cellular dynamics of HIV infection. But challenges remain.
      Treatment does not suppress HIV replication in all patients, and the emergence of
      drug-resistant virus hinders subsequent treatment. Chronic therapy can also
      result in toxicity. These challenges prompt the search for new drugs and new
      therapeutic strategies to control chronic viral replication.

PMID- 11309631
TI  - Challenges and opportunities for development of an AIDS vaccine.
AB  - Among the devastating consequences of AIDS has been its epidemic spread in the
      developing world. The disease has caused unprecedented suffering, debilitation,
      loss of life and disruption of family, social and economic stability. Because of
      the considerable expense and logistical difficulty in providing antiviral drugs
      to populations infected with the human immunodeficiency virus throughout the
      world, the biomedical community is looking towards vaccines to help solve this
      compelling problem.

PMID- 11309632
TI  - Effect of early or delayed insertion of tympanostomy tubes for persistent otitis
      media on developmental outcomes at the age of three years.
AB  - BACKGROUND: A main indication for the insertion of tympanostomy tubes in infants
      and young children is persistent otitis media with effusion, reflecting concern
      that this condition may cause lasting impairments of speech, language, cognitive,
      and psychosocial development. However, evidence of such relations is
      inconclusive, and evidence is lacking that the insertion of tympanostomy tubes
      prevents developmental impairment. METHODS: We enrolled 6350 healthy infants from
      2 to 61 days of age and evaluated them regularly for middle-ear effusion. Before
      the age of three years 429 children with persistent effusion were randomly
      assigned to have tympanostomy tubes inserted either as soon as possible or up to
      nine months later if effusion persisted. In 402 of these children we assessed
      speech, language, cognition, and psychosocial development at the age of three
      years. RESULTS: By the age of three years, 169 children in the early-treatment
      group (82 percent) and 66 children in the late-treatment group (34 percent) had
      received tympanostomy tubes. There were no significant differences between the
      early-treatment group and the late-treatment group at the age of three years in
      the mean (+/-SD) scores on the Number of Different Words test, a measure of word
      diversity (124+/-32 and 126+/-30, respectively); the Percentage of Consonants
      Correct-Revised test, a measure of speech-sound production (85+/-7 vs. 86+/-7);
      the General Cognitive Index of McCarthy Scales of Children's Abilities (99+/-14
      vs. 101+/-13); or on measures of receptive language, sentence length, grammatical
      complexity, parent-child stress, and behavior. CONCLUSIONS: In children younger
      than three years of age who have persistent otitis media, prompt insertion of
      tympanostomy tubes does not measurably improve developmental outcomes at the age
      of three years.

PMID- 11309633
TI  - The role of adjuvant adenoidectomy and tonsillectomy in the outcome of the
      insertion of tympanostomy tubes.
AB  - BACKGROUND: Otitis media is the most common medical problem in young children.
      The usual surgical treatment is myringotomy with insertion of tympanostomy tubes.
      There is debate about the usefulness of concomitant adenoidectomy or
      adenotonsillectomy. We examined the effects of these adjuvant procedures on the
      rates of reinsertion of tympanostomy tubes and rehospitalization for conditions
      related to otitis media. METHODS: Using hospital discharge records for the period
      1995 through 1997, we examined the results of surgery for all 37,316 children
      (defined as persons 19 years of age or younger) in Ontario, Canada, who received
      tympanostomy tubes as their first surgical treatment for otitis media. We
      determined the time to the first readmission for conditions related to otitis
      media and the time to the first reinsertion of tympanostomy tubes. RESULTS: As
      compared with treatment involving the insertion of tympanostomy tubes alone,
      adjuvant adenoidectomy was associated with a reduction in the likelihood of
      reinsertion of tympanostomy tubes (relative risk, 0.5; 95 percent confidence
      interval, 0.5 to 0.6; P<0.001) and the likelihood of readmission for conditions
      related to otitis media (relative risk, 0.5; 95 percent confidence interval, 0.5
      to 0.6; P<0.001). The risk of these outcomes was further reduced if an adjuvant
      adenotonsillectomy was performed. The effect was age-related. Children as young
      as one year appeared to benefit from adjuvant adenotonsillectomy; the benefit of
      an adjuvant adenoidectomy was apparent in two-year-olds and was greatest for
      children three years of age or older. CONCLUSIONS: Performing an adenoidectomy at
      the time of the initial insertion of tympanostomy tubes substantially reduces the
      likelihood of additional hospitalizations and operations related to otitis media
      among children two years of age or older.

PMID- 11309635
TI  - Cognitive function in postmenopausal women treated with raloxifene.
AB  - BACKGROUND: In postmenopausal women, estrogen may have a beneficial effect on
      cognition or reduce the risk of decline in cognitive function. Whether
      raloxifene, a selective estrogen-receptor modulator, might have similar actions
      is not known. METHODS: As part of the Multiple Outcomes of Raloxifene Evaluation
      trial, we studied 7478 postmenopausal women with osteoporosis (mean age, 66
      years), who were enrolled at 178 sites in 25 countries. The women were randomly
      assigned to receive raloxifene (60 mg or 120 mg) or placebo daily for three
      years. We compared the mean scores of the groups on six tests of cognitive
      function, which were administered at base line and at six months and one, two,
      and three years. Women were classified as having a decline in cognitive function
      if the change in their scores at three years was in the worst 10 percent.
      RESULTS: The mean cognitive scores in the three groups of women were similar at
      base line. The scores improved slightly in all three groups during the three-year
      study period, with no significant differences among the groups. The risk of
      decline in the cognitive function, as measured by four of the six tests, did not
      differ significantly between the two raloxifene groups combined and the placebo
      group, but there was a trend toward less decline in the combined raloxifene group
      on the two tests of verbal memory (relative risk, 0.77) and attention, (relative
      risk, 0.87). Newly reported or worsening hot flashes did not negatively influence
      test scores or the effect of treatment on test performance. CONCLUSIONS:
      Raloxifene treatment for three years does not affect overall cognitive scores in
      postmenopausal women with osteoporosis.

PMID- 11309634
TI  - Molecular predictors of survival after adjuvant chemotherapy for colon cancer.
AB  - BACKGROUND: Adjuvant chemotherapy improves survival among patients with stage III
      colon cancer, but no reliable molecular predictors of outcome have been
      identified. METHODS: We evaluated loss of chromosomal material (also called loss
      of heterozygosity or allelic loss) from chromosomes 18q, 17p, and 8p; cellular
      levels of p53 and p21(WAF1/CIP1) proteins; and microsatellite instability as
      molecular markers. We analyzed tumor tissue from 460 patients with stage III and
      high-risk stage II colon cancer who had been treated with various combinations of
      adjuvant fluorouracil, leucovorin, and levamisole to determine the ability of
      these markers to predict survival. RESULTS: Loss of heterozygosity at 18q was
      present in 155 of 319 cancers (49 percent). High levels of microsatellite
      instability were found in 62 of 298 tumors (21 percent), and 38 of these 62
      tumors (61 percent) had a mutation of the gene for the type II receptor for
      transforming growth factor beta1 (TGF-beta1). Among patients with microsatellite
      stable stage III cancer, five-year overall survival after fluorouracil-based
      chemotherapy was 74 percent in those whose cancer retained 18q alleles and 50
      percent in those with loss of 18q alleles (relative risk of death with loss at
      18q, 2.75; 95 percent confidence interval, 1.34 to 5.65; P=0.006). The five-year
      survival rate among patients whose cancer had high levels of microsatellite
      instability was 74 percent in the presence of a mutated gene for the type II
      receptor for TGF-beta1 and 46 percent if the tumor did not have this mutation
      (relative risk of death, 2.90; 95 percent confidence interval, 1.14 to 7.35;
      P=0.03). CONCLUSIONS: Retention of 18q alleles in microsatellite-stable cancers
      and mutation of the gene for the type II receptor for TGF-beta1 in cancers with
      high levels of microsatellite instability point to a favorable outcome after
      adjuvant chemotherapy with fluorouracil-based regimens for stage III colon
      cancer.

PMID- 11309636
TI  - Images in clinical medicine. Superficial thrombophlebitis.

PMID- 11309637
TI  - The diagnosis of brain death.

PMID- 11309638
TI  - Genetic susceptibility to venous thrombosis.

PMID- 11309639
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 12-2001. A 16-year-old boy with an altered mental status and
      muscle rigidity.

PMID- 11309640
TI  - Should we operate on children with fluid in the middle ear?

PMID- 11309641
TI  - Can estrogen or selective estrogen-receptor modulators preserve cognitive
      function in elderly women?

PMID- 11309642
TI  - Brain death--well settled yet still unresolved.

PMID- 11309643
TI  - Anxiety at the frontier of molecular medicine.

PMID- 11309644
TI  - Frequency with which surgeons undertake pancreaticoduodenectomy determines length
      of stay, hospital charges, and in-hospital mortality.
AB  - Others have suggested that in certain technically challenging operations, outcome
      and experience are related. Because pancreaticoduodenectomy is a technically
      complex procedure, this study was undertaken to evaluate mortality, length of
      hospital stay, and hospital charges when compared to volume of experience. The
      database of the State of Florida Agency for Health Care Administration was
      queried for pancreaticoduodenectomies undertaken during a recent 33-month period.
      Length of stay, hospital charges, and in-hospital mortality were stratified by
      the frequency of pancreaticoduodenectomy. A total of 282 surgeons performed 698
      pancreaticoduodenectomies over 33 months. Eighty-nine percent of surgeons
      performed one pancreaticoduodenectomy per year or less and accounted for 52% of
      the procedures. Overall mortality rate was 5.1%. Average hospital charges were
      &dollar;72,171.64. The more frequently pancreaticoduodenectomy was undertaken,
      the shorter the hospital stay (P = 0.025, regression analysis) and the lower the
      hospital charges (P = 0.008, regression analysis) and in-hospital mortality (P =
      0.036, log likelihood ratio test). Surgeons who undertake pancreaticoduodenectomy
      more frequently have patients with shorter hospital stays, lower hospital
      charges, and lower in-hospital mortality rates, independent of hospital volume.
      Variations exist among surgeons and among different areas of the state. Data
      regarding cost and mortality are available for use in programs of cost and
      quality improvement.

PMID- 11309645
TI  - Preoperative chemoradiation for marginally resectable adenocarcinoma of the
      pancreas.
AB  - Only 10% to 20% of patients with pancreatic cancer are considered candidates for
      curative resection at the time of diagnosis. We postulated that preoperative
      chemoradiation therapy might promote tumor regression, eradicate nodal
      metastases, and allow for definitive surgical resection in marginally resectable
      patients. The objective of this study was to evaluate the effect of a
      preoperative chemoradiation therapy regimen on tumor response, resectability, and
      local control among patients with marginally resectable adenocarcinoma of the
      pancreas and to report potential treatment-related toxicity. Patients with
      marginally resectable adenocarcinoma of the pancreas (defined as portal vein,
      superior mesenteric vein, or artery involvement) were eligible for this protocol.
      Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent
      protracted venous infusion of 5-fluorouracil (250 mg/m2/day). Reevaluation for
      surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men
      and 6 women) completed preoperative chemoradiation without interruption. One
      patient required a reduction in the dosage of 5-fluorouracil because of
      stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea,
      vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and
      hematologic suppression. CA 19-9 levels declined in all nine of the patients with
      elevated pretreatment levels. Nine of the 15 patients underwent a
      pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these
      patients had a complete pathologic response, and two had microscopic involvement
      of a single lymph node. With a median follow-up of 30 months, the median survival
      for resected patients was 30 months, whereas in the unresected group median
      survival was 8 months. Six of the nine patients who underwent resection remain
      alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months,
      respectively. Preoperative chemoradiation therapy is well tolerated. It may
      downstage tumors, sterilize regional lymph nodes, and improve resectability in
      patients with marginally resectable pancreatic cancer. Greater patient accrual
      and longer follow-up are needed to more accurately assess its future role in
      therapy.

PMID- 11309646
TI  - Complete fundoplication is not associated with increased dysphagia in patients
      with abnormal esophageal motility.
AB  - Abnormal esophageal motility is a relative contraindication to complete (360
      degree) fundoplication because of a purported risk of postoperative dysphagia.
      Partial fundoplication, however, may be associated with increased postoperative
      esophageal acid exposure. Our aim was to determine if complete fundoplication is
      associated with increased postoperative dysphagia in patients with abnormal
      esophageal motor function. Medical records of 140 patients (79 females; mean age
      48 +/- 1.1 years) who underwent fundoplication for gastroesophageal reflux
      disease (GERD) were reviewed retrospectively to document demographic data,
      symptoms, and diagnostic test results. Of the 126 patients who underwent complete
      fundoplication, 25 met manometric criteria for abnormal esophageal motility (#30
      mm Hg mean distal esophageal body pressure or #80% peristalsis), 68 had normal
      esophageal function, and 33 had incomplete manometric data and were therefore
      excluded from analysis. Of the 11 patients who underwent partial fundoplication,
      eight met criteria for abnormal esophageal motility, two had normal esophageal
      function, and one had incomplete data and was therefore excluded. After a median
      follow-up of 2 years (range 0.5 to 5 years), patients were asked to report
      heartburn, difficulty swallowing, and overall satisfaction using a standardized
      scoring scale. Complete responses were obtained in 72%. Sixty-five patients who
      underwent complete fundoplication and had manometric data available responded (46
      normal manometry; 19 abnormal manometry). Outcomes were compared using the Mann
      Whitney U test. After complete fundoplication, similar postoperative heartburn,
      swallowing, and overall satisfaction were reported by patients with normal and
      abnormal esophageal motility. Likewise, similar outcomes were reported after
      partial fundoplication. This retrospective study found equally low dysphagia
      rates regardless of baseline esophageal motility; therefore a randomized trial
      comparing complete versus partial fundoplication in patients with abnormal
      esophageal motility is warranted.

PMID- 11309647
TI  - Five- to eight-year outcome of the first laparoscopic Nissen fundoplications.
AB  - The operative mortality and morbidity of laparoscopic fundoplication are lower
      than for the open procedure. Questions have been raised regarding its long-term
      durability. One hundred seventy-one patients who had undergone laparoscopic
      Nissen fundoplication at least 5 years previously answered a questionnaire.
      During this period, 291 patients underwent a laparoscopic Nissen fundoplication.
      Surveillance data were available for 171 patients at a mean of 6.4 years after
      surgery. Overall, 96.5% were satisfied and 3.5% were not satisfied with the
      result of the procedure. Persistent symptoms included abdominal bloating (20.5%),
      diarrhea (12.3%), regurgitation (6.4%), heartburn (5.8%) and chest pain (4.1%);
      27.5% reported dysphagia, and 7% had required dilatation. Fourteen percent were
      on continuous proton pump inhibitor therapy, but 79% of these patients were
      treated for vague abdominal or chest symptoms unrelated to reflux, which calls
      into question the indications for this therapy. Ninety-three percent of all
      patients were satisfied with their decision to have surgery. The overall well
      being score increased significantly from 2.2 +/- 1.6 before surgery to 8.8 +/- 2
      (P > 0.0001) at more than 5 years after surgery. Twenty-one percent had undergone
      additional diagnostic procedures after surgery such as endoscopy and/or barium
      swallow. Laparoscopic Nissen fundoplication is an excellent long-term treatment
      for gastroesophageal reflux disease with persistent success for more than 5
      years. Some patients have continuing symptoms and remain on therapy, but more
      than 90% of all patients undergoing laparoscopic Nissen fundoplication remain
      satisfied with their decision to have surgery. These results are at least as good
      as those achieved with open fundoplication and prove the long-term worth of this
      procedure.

PMID- 11309648
TI  - Thyroid hormone and the d-type cyclins interact in regulating enterocyte gene
      transcription.
AB  - Thyroid hormone (T3) is an important regulator of gut mucosal development and
      differentiation, inducing intestinal alkaline phosphatase (IAP) and repressing
      lactase gene transcription. In contrast, cyclin D1 (CD1) appears to be a growth
      promoter in the gut, functioning to maintain the undifferentiated state. The
      present studies were designed to examine the effects of CD1 on T3 action within
      intestinal epithelia. Caco-2 cells were maintained in hypothyroid medium and
      transiently transfected with either rat lactase (3.0 kb) or human IAP (2.4 kb)
      luciferase (Luc) reporter plasmids. Cotransfections were carried out using two T3
      receptor (TR) isoforms, TR"-1 and TR$-1, as well as plasmids expressing CD1, CD3,
      CA, or CB1. Cells were then treated +/- 10 nmol/L T3 for 24 hours and luciferase
      activity was determined. With T3 treatment, IAP-Luc activity was induced (TR"-1 =
      eightfold, TR$-1 = ninefold), but these effects were dramatically inhibited (>
      50%) by CD1 and CD3. In contrast, CA and CB1 did not alter T3-mediated IAP gene
      activation. The ability of CD1 and CD3 to inhibit T3 action was also tested in
      the context of the lactase gene, which is negatively regulated by T3. As
      expected, lactase reporter gene activity was repressed by T3 treatment in the
      case of both receptor isoforms, TR"-1 = 30% and TR$-1 = 40%. In contrast to its
      effects on the IAP gene, CD1 did not inhibit T3-mediated changes in lactase
      reporter gene activity. The D-type cyclins (CD1 and CD3), but not CA or CB1,
      specifically inhibit T3-mediated activation of the IAP gene. In contrast, the D
      type cyclins do not inhibit T3-mediated repression of the lactase gene. These
      studies have identified a novel molecular interaction that exists between the
      pathways of growth and differentiation within intestinal epithelia.

PMID- 11309649
TI  - Sensitization of human colon cancer cells to TRAIL-mediated apoptosis.
AB  - TNF-related apoptosis-inducing ligand (TRAIL), a novel member of the tumor
      necrosis factor (TNF) family, is thought to induce apoptosis preferentially in
      cancer cells; however, increasing evidence suggests that a number of cancers are
      resistant to TRAIL treatment. FLICE-like inhibitory protein (FLIP), which
      structurally resembles caspase-8, can act as an inhibitor of apoptosis when
      expressed at high levels in certain cancer cells. The purpose of our present
      study was to determine whether human colon cancer cells are sensitive to TRAIL
      treatment and, if not, to identify potential mechanisms of resistance. Colon
      cancer cells of different metastatic potential (KM12C, KML4A, and KM20) were
      found to be resistant to the effects of TRAIL when used as a single agent. FLIP
      expression levels were increased in all three KM cell lines. Treatment with
      either actinomycin D (Act D;10 :g/ml) or cycloheximide (CHX; 10 :g/ml) decreased
      FLIP expression levels in all three cell lines. The decrease in cellular levels
      of FLIP was associated with sensitization to TRAIL-mediated apoptosis, as
      demonstrated by enhanced cell death and caspase-3 activity compared with either
      Act D or CHX alone. Our findings suggest that reduction of FLIP levels by Act D
      or CHX renders TRAIL-resistant human colon cancer cells sensitive to TRAIL
      mediated apoptosis. The combination of TRAIL along with agents such as Act D or
      CHX, which target proteins that prevent cell death, may provide a more effective
      and less toxic regimen for treatment of resistant colon cancers.

PMID- 11309650
TI  - Laparoscopic-assisted vs. open colectomy for colorectal cancer: influence on
      neoplastic cell mobilization.
AB  - Laparoscopic surgery for treatment of colorectal cancer has been suggested to
      enhance tumor dissemination. Recently, molecular techniques have been developed
      to detect micrometastatic disease in patients with solid tumors, with a higher
      accuracy than cytologic or immunohistochemical approaches. This study was
      undertaken to investigate the potential harmful effects of laparoscopic-assisted
      colectomy on neoplastic cell mobilization in patients with resectable colorectal
      cancer. Fifty patients with nonmetastatic colorectal cancer were randomly
      assigned to laparoscopic-assisted (LAC, n = 26) or open (OC, n = 24) colectomy.
      Peripheral venous blood samples were obtained preoperatively, immediately after
      tumor removal, and 24 hours later. In 10 patients from each treatment group,
      portal blood and peritoneal fluid samples were also obtained before and after
      resection. Neoplastic cells were detected by means of reverse transcriptase
      polymerase chain reaction targeted to carcinoembryonic antigen (CEA)
      transcription. CEA mRNA was detected in peripheral venous blood samples from 35
      of 50 colorectal cancer patients preoperatively. Among those 15 baseline-negative
      patients, four experienced conversion 24 hours after tumor resection (2 [33%] of
      6 in the LAC group vs. 2 [22%] of 9 in the OC group; NS). At that time point,
      clearance of CEA mRNA expression was observed in 14 of the 35 baseline-positive
      patients (9 [45%] of 20 in the LAC group vs. 5 [33%] of 15 in the OC group; NS).
      In addition, only one patient in the LAC group with baseline-negative CEA mRNA
      expression experienced portal blood conversion after tumor removal, although his
      peripheral blood level remained negative. Finally, baseline peritoneal fluid CEA
      mRNA expression was never detected, but one patient in each group became positive
      postoperatively. These results confirm that preoperative and perioperative
      mobilization of neoplastic cells is a frequent occurrence in patients with
      colorectal cancer, but the surgical approach (LAC vs. OC) does not seem to be a
      determining factor.

PMID- 11309651
TI  - Laparoscopic endobiliary stenting: a simplified approach to the management of
      occult common bile duct stones.
AB  - Three years ago we described laparoscopic placement of biliary stents as an
      adjunct to laparoscopic common bile duct exploration (LCBDE) in 16 patients. We
      now present a modification of our technique and experience with 48 additional
      patients. Laparoscopic cholecystectomy with intraoperative fluorocholangiography
      (LC/IOC) performed in 372 consecutive patients during a 36-month period revealed
      common bile duct stones (CBDS) in 48 patients (12.9%). In this series, LCBDE was
      not performed and no attempt was made to clear CBDS prior to transcystic stent
      placement. Stent placement added 9 to 26 minutes of operative time to LC/IOC
      alone. Forty-four patients (92%) were discharged after surgery and four (8%) were
      observed overnight. Outpatient endoscopic retrograde cholangiopancreatography 1
      to 4 weeks later succeeded in clearing CBDS in all patients. All stents were
      retrieved without difficulty and 3- to 36-month follow-up demonstrates no
      surgical, endoscopic, or stent-related complications to date. Laparoscopic
      biliary stent placement for the treatment of CBDS is a safe, rapid, technically
      less challenging alternative to existing methods of LCBDE. It preserves the
      benefits of minimally invasive surgery for patients, and virtually assures
      success of postoperative endoscopic retrograde cholangiopancreatography with
      complete stone clearance.

PMID- 11309652
TI  - Functional interleukin-4 receptor and interleukin-2 receptor common gamma chain
      in human gastric carcinoma: a possible mechanism for cytokine-based therapy.
AB  - Interleukin (IL)-2 and IL-4 play a critical role in the regulation of the immune
      response. Yet both of the receptors for these cytokines have been found on
      nonhematopoietic cells, including human gastric carcinoma cell lines and tissue
      specimens. IL-4 causes G1 phase cell cycle arrest of gastric carcinoma; the
      effect directly correlates with the expression of IL-4 receptor (IL-4R) and is
      seen within 48 hours after treatment. Cells lacking IL-4R are unaffected by IL-4.
      We examined signal transduction pathways employed by IL-4 that may account for
      cell cycle arrest of an established human gastric carcinoma cell line, CRL 1739.
      Western blot analysis was performed on CRL 1739 cultured in the presence of IL-4
      (500 U/ml). Cells were lysed, protein extracted, and electroblotted; blots were
      then probed with murine mono-clonal antibodies to specific intracellular
      proteins. Western blotting of CRL 1739 with antiphosphotyrosine antibody (4G10)
      demonstrated multiple (140 kDa and 65 kDa) phosphoproteins seen only in IL-4
      treated CRL 1739. Immunoprecipitation and blotting of CRL 1739 with specific
      secondary antibodies demonstrated that the 140 kDa phosphoprotein was IL-4R", the
      65kDa phosphoprotein was IL-2Rgc, the 130 kDa phosphoprotein was Janus kinase
      (JAK1), and the 116 kDa phosphoprotein was JAK3. Reverse transcription-polymerase
      chain reaction with specific primers demonstrated that multiple human gastric
      tumor specimens expressed IL-4R" and IL-2Rgc but did not express the leukocyte
      marker CD45. These results suggest that human gastric carcinomas may express
      functional cytokine receptors, including the IL-2Rgc commonly found in
      association with the lymphocyte IL-2R. These receptors may represent novel
      targets for directing cytokine-based therapy.

PMID- 11309654
TI  - Ablation of liver metastasis: is preoperative imaging sufficiently accurate?
AB  - The recent introduction of cryotherapy and radiofrequency ablation of liver
      metastasis has expanded the indications for treatment. As technology has
      advanced, a percutaneous approach has been developed. Percutaneous treatment,
      however, requires accurate preoperative imaging. From 1993 to 1999, 179 patients
      underwent operative exploration for treatment of suspected hepatic metastases
      from colorectal carcinoma. One hundred seventy-seven patients were staged by
      preoperative CT, two patients were staged by MRI, and complete data were
      available in 176. Hepatic tumor count by preoperative imaging was compared to
      intraoperative tumor count obtained by inspection, palpation, ultrasonographic
      examination using a 3.5/7.5 MHz T probe, and careful gross sectioning of the
      resected specimen. Post hoc analysis was performed on 35 CT scans by two
      radiologists who specialize in abdominal CT. These radiologists were blinded to
      the intraoperative findings. Their interpretations were compared to the
      intraoperative counts and to each other. Thirty-four (19%) of 179 patients were
      deemed untreatable at operation because of unsuspected overwhelming liver
      involvement in 11 (6%) or extrahepatic metastases in 23 (13%). For the group, CT
      was accurate in 80 patients (45%), showed more lesions than were found in 16
      (9%), and showed fewer metastases than were found in 80 (45%). When the
      preoperative scan predicted a solitary metastasis, it was correct in 45 (65%) of
      69 patients and underestimated disease in 24 (35%). In the post hoc analysis, the
      mean numbers of lesions reported by the two radiologists did not differ from the
      mean number of tumors found; however, the radiologists' counts agreed on 16 (59%)
      and disagreed on 11 (41%) of the scans. The accuracy of CT decreased with
      increasing numbers of lesions. Regardless of the type of preoperative imaging,
      intraoperative findings altered the course of the operation in 96 (55%) of 176
      patients. Preoperative imaging is not sufficiently accurate to permit adequate
      percutaneous treatment of hepatic metastases from colorectal carcinoma.

PMID- 11309653
TI  - The antioxidant n-acetylcysteine increases 5-fluorouracil activity against
      colorectal cancer xenografts in nude mice.
AB  - The antioxidant pyrrolidinedithiocarbamate improves the therapeutic efficacy of 5
      fluorouracil (5-FU) against HCT-15 colorectal cancer cell line xenografts in nude
      mice without increasing toxicity to normal intestinal or hematopoietic tissues.
      In the current study we have shown that a similar clinically licensed
      antioxidant, N-acetylcysteine (200 mg/kg), can modulate the activity of 5-FU (120
      mg/kg) against HCT-15 tumor xenografts in nude mice. We demonstrate that this
      effect is accompanied by a sustained elevation in p53-independent apoptosis
      without accompanying alterations in cell cycle kinetics. Extensive tumor necrosis
      is also a prominent feature of treatment; however, no significant impairment of
      neovascularization as assessed by intratumor microvessel density occurred. We
      believe that the clinical efficacy of N-acetylcysteine as an adjunct to 5-FU in
      advanced colorectal cancer should be investigated further.

PMID- 11309655
TI  - Enhancing release of peptide YY after near-total proctocolectomy: jejunal pouch
      vs. ileal pouch-distal rectal anastomosis.
AB  - Reconstructing the enteric tract after near-total proctocolectomy by interposing
      a jejunal pouch between the distal ileum and the distal rectum slows small
      intestinal transit and decreases the number of stools per day compared to a
      conventional ileal pouch-distal rectal reconstruction. Our hypothesis was that
      the jejunal pouch operation brings about these results by protecting the ability
      of the ileal mucosa to secrete peptide YY, thus augmenting the hormonal ileal
      brake on small intestinal transit and decreasing the stool frequency. In five
      jejunal pouch dogs and five ileal pouch dogs, more than 6 months after the
      operation, serum peptide YY concentrations were determined before and at 30
      minute intervals for 180 minutes after a standard meal. Fasting serum
      concentrations of peptide YY, measured by radioimmunoassay, were greater in
      jejunal pouch dogs (mean +/- SEM, 1340 +/- 143 pg/ml) than in ileal pouch dogs
      (804 +/- 52 pg/ml; P < 0.01). Postprandial peptide YY concentrations in jejunal
      pouch dogs were also greater at 30 minutes (jejunal pouch = 1524 +/- 131 pg/ml,
      ileal pouch = 913 +/- 67 pg/ml; P = 0.01) and 60 minutes after the meal (jejunal
      pouch = 1723 +/- 250 pg/ml, ileal pouch = 1001 +/- 70 pg/ml; P = 0.05) and peaked
      sooner (jejunal pouch = 81 +/- 17 minutes, ileal pouch = 147 +/- 12 minutes; P =
      0.01). We concluded that the jejunal pouch operation results in greater ileal
      fasting and postprandial secretion of peptide YY than the ileal pouch operation.
      The greater release may account, in part, for the slower small bowel transit and
      decreased number of stools after the jejunal pouch operation.

PMID- 11309656
TI  - The battle of two genomes: genetics of bacterial host/pathogen interactions in
      mice.
AB  - Genetic factors strongly determine the outcome of infectious diseases caused by
      various pathogens. The molecular mechanisms of resistance and susceptibility in
      humans, however, remains largely unknown. Complex interactions of multiple genes
      that control the host response to a pathogen further complicate the picture.
      Animal models have a tremendous potential to dissect the complex genetic system
      of host-pathogen interaction into single components. This is particularly true
      for the mouse, which will continue to develop into an invaluable tool in the
      identification and cloning of host resistance genes. Three main approaches have
      been taken to establish mouse models for human infectious diseases: 1) Production
      of mouse mutants by gene targeting; 2) positional cloning of host-resistance
      genes in mutant mice; and 3) mapping and characterization of quantitative trait
      loci (QTL) controlling the complex aspects of host-pathogen interactions. The
      contribution of all three methods to the understanding of infectious diseases in
      humans will be reviewed in this work, with a special emphasis on the studies of
      resistance/susceptibility mechanism in bacterial infections.

PMID- 11309657
TI  - Quantitative trait locus analysis of abnormal circadian period in CS mice.
AB  - CS mice show a free-running period (tau) longer than 24 h and rhythm splitting in
      constant darkness (DD). These features in behavioral circadian rhythms are
      distinctive as compared with other inbred strains of mice, which exhibit robust
      free-running rhythms with T shorter than 24 h. To identify the genes affecting
      tau, quantitative trait locus (QTL) analysis was initially conducted by using 289
      F2 mice derived from a cross between CS and C57BL/6J strain. A suggestive QTL
      (LOD = 3.71) with CS allele increasing tau was detected on the distal region of
      Chromosome (Chr) 19. Next, using 192 F2 mice from a cross between CS and MSM
      strain, the presence of the QTL on Chr 19 was examined, and we confirmed the QTL
      at the genome-wide significant level (LOD = 4.61 with 10.4% of the total variance
      explained). This QTL was named long free-running period (Lfp). Three other
      suggestive QTLs (LOD = 3.24-4.28) were mapped to the midportion of Chr 12 in
      (CSxC57BL/6J)F2 mice, and to the proximal and middle region of Chr 19 in
      (CSxMSM)F2 mice, respectively, of which, CS alleles for two QTLs on Chr 19 have
      the effect of lengthening tau. None of these QTLs were mapped to the chromosomal
      regions of previously described QTLs for tau and known clock genes (Clock, mPer1,
      Bmal1, mCrv1, mCry2, mTim, and Csnk1e).

PMID- 11309658
TI  - Two interactive genes responsible for a new inherited cataract (RCT) in the
      mouse.
AB  - We discovered a mutant mouse, RCT (Rinshoken cataract), with a new congenital
      cataract in strain SJL/J. The opacity of the lens associated with microphthalmia
      could be observed visually at 3 to 3.5 months of age. Marked degeneration of the
      lens, including loss of the fine structure of the lens fibers and swelling of
      epithelial cells with vacuoles of various sizes in the cortex, but no other
      defects except photoreceptor degeneration in the retina, was detected.
      Histological change in the lens was first observed at 2 days after birth. No sex
      related differences were detected, and normal phenotypes in the F1 progeny of RCT
      and normal mice indicated that the cataract was recessive. The chromosomal
      location of the causative gene was determined by interval mapping by using
      intersubspecific backcross progeny of RCT and MSM/Ms, an inbred strain from the
      Japanese wild mouse Mus musculus molossinus. Backcross progeny were divided into
      three groups according to phenotype: mice (1) with an early-onset cataract, which
      can be detected visually as in RCT mice, (2) with a late-onset cataract, which
      can be detected histologically but not visually, and (3) with a normal lens.
      Three phenotypes were found to be expressed by allele combinations of two
      recessive genes, rct and mrct (a modifier of rct). The rct locus essential for
      the onset of the cataract was tightly linked to D4Mit278 on Chromosome (Chr) 4
      with no recombination. The mrct locus was closely linked to D5Mit239 (chi2 =
      66.3, P << 0.00001) on Chr 5.

PMID- 11309659
TI  - Quantitative trait loci affecting growth in high growth (hg) mice.
AB  - A genome-wide scan was performed in order to identify Quantitative Trait Loci
      (QTL) associated with growth in a population segregating high growth (hg), a
      partially recessive mutation that enhances growth rate and body size in the
      mouse. A sample of 262 hg/hg mice was selected from a C57BL/6J-hg/hg x CAST/EiJ
      F2 cross and typed with 79 SSLP markers distributed across the genome. Eight
      significant loci were identified through interval mapping. Loci on Chromosomes
      (Chrs) 2 and 8 affected the growth rate of F2 mice. Loci on Chr 2 and 11 affected
      growth rate and carcass lean mass (protein and ash). A locus on Chr 9 modified
      femur length and another one in Chr 17 affected both carcass lean mass and femur
      length, but none of these had significant effects on growth rate. Loci on Chrs 5
      and 9 modified carcass fat content. Additive effects were positive for C57BL/6J
      alleles, except for the two loci affecting carcass fatness. Typing of selected
      markers in 274 +/+ F2 mice revealed significant interactions between hg and other
      growth QTL, which were detected as changes in gene action (additive or dominant)
      and in allele substitution effects. Knowledge about interactions between loci,
      especially when major genes are involved, will help in the identification of
      positional candidate genes and in the understanding of the complex genetic
      regulation of growth rate and body size in mammals.

PMID- 11309660
TI  - Use of intercross outbred mice and single nucleotide polymorphisms to map skin
      cancer modifier loci.
AB  - Car-R and Car-S outbred mouse lines, phenotypically selected for resistance and
      susceptibility to skin carcinogenesis respectively, show significant linkage
      disequilibrium (LD) at genetic markers mapping on chromosomal regions where skin
      cancer modifier loci (Skts3, Skts1, and Psl1 on Chrs 5, 7, and 9 respectively)
      have been mapped in standard crosses. Analysis of these regions for genetic
      linkage with skin cancer phenotypes in 245 (Car-R x Car-S)F2 intercross mice, by
      using single nucleotide polymorphisms (SNPs), revealed significant linkage at a
      possible allelic form of the Skts1 locus, whose mapping region was shortened to a
      <5.5-cM interval near the Tyr locus. The Car-derived Skts1 locus was linked with
      papilloma multiplicity and latency by a recessive inheritance of the
      susceptibility allele. Putative loci on Chr 5 (Skts3) and 9 (Psl1) showed no
      significant linkage. These results point to the important role of the Stks1 locus
      in mouse skin tumorigenesis in independent crosses. The shortened Skts1 mapping
      region should facilitate the identification of candidate genes.

PMID- 11309662
TI  - Detection of quantitative trait loci for meat quality in a commercial slaughter
      pig cross.
AB  - The primary goal of this study was to localize quantitative trait loci (QTL)
      affecting meat quality traits in swine. In total, 42 traits were scored on 305 F2
      individuals from a commercial slaughter pig cross in Norway. F1 and F2
      individuals were genotyped for 29 markers on Chromosomes (Chrs) 4, 6, and 7,
      since previous studies had revealed QTL affecting meat quality traits on these
      chromosomes. The most evident result was detection of a QTL affecting amount of
      intramuscular fat on Chr 6. The QTL might also influence tenderness, whereas no
      effect was observed for back-fat thickness. Additionally, suggestive evidence for
      QTL affecting other meat quality traits was found on Chr 4 and Chr 7.

PMID- 11309661
TI  - Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive
      rat.
AB  - It has recently been proposed that primary mutations in genes involved in fatty
      acid and lipid metabolism may contribute to the pathogenesis of insulin
      resistance and dyslipidemia often observed in spontaneous forms of hypertension.
      In the current study in the spontaneously hypertensive rat (SHR), we mapped and
      sequenced the gene encoding a key transcription factor known as ADD1 (adipocyte
      determination and differentiation factor 1) or SREBP-1c (sterol regulatory
      element binding protein- c) that has recently been identified as a master
      regulator of genes involved in the hepatic control of lipid and carbohydrate
      metabolism. We found that (1) the gene for ADD1/SREBP-1c maps to a region of rat
      Chromosome 10 previously reported to contain a quantitative trait locus involved
      in the regulation of hepatic cholesterol levels and (2) the SHR harbors a valine
      to-methionine substitution in the COOH terminal portion of the ADD1/SREBP-1
      protein that is not present in 44 other strains of laboratory rats. These
      findings, together with previous studies showing that transgenic expression of
      SREBP-1 isoforms has major effects on hepatic fatty acid and cholesterol
      biosynthesis, suggest that naturally occurring variation in the gene encoding the
      SREBP-1 isoforms might contribute to inherited variation in lipid metabolism in
      the SHR versus other strains of rats. These results should serve to motivate
      future transfection studies of the effect of the SHR mutant on SREBP-1 expression
      and activation in vitro, as well as the development of congenic and transgenic
      strains of SHR to investigate the effects of different variants of SREBP-1 on
      carbohydrate and lipid metabolism in vivo.

PMID- 11309663
TI  - Characterization of a SINE species from vicuna and its distribution in animal
      species including the family Camelidae.
AB  - Twenty-six sequences of a short interspersed repetitive element (SINE) with a
      size of approximately 150 base pairs (bp) were isolated from the genomic DNA of
      Vicugna vicugna (vicuna). RNA polymerase III split promoter sequence was observed
      in most of them, and many had direct repeats flanking to SINEs as well as a
      poly(A)-like structure. The SINE sequences were designated as "vic-1" sequences.
      Comparison of the vic-1 consensus sequence with sequences registered in the DNA
      database (DDBJ/ EMBL/GENBANK) revealed that the vic-1 sequence had a 79% homology
      with mouse ala-tRNA gene. In addition, the tRNA-related region of the consensus
      sequence was folded into a cloverleaf structure as with mouse ala-tRNA. These
      findings strongly indicated that vic-1 was a retroposon derived from ala-tRNA
      gene. The vic-1 sequences were used as a probe for dot-blot hybridization to
      examine the distribution of their homologous sequences in the genomes of various
      animal species spanning 14 orders, of which, homologous sequences were found only
      in the Camelidae family. In order to examine the phylogenetical relationship
      among vicuna, llama, and camel, vic-1 insertion analysis and homology analysis of
      vic-1 sequences were performed at each locus. The analyses indicated that vic-1
      sequences were generated in a common ancestor of the animal species, and that
      camels first branched off from the clade Camelidae, followed by vicunas and
      llamas.

PMID- 11309664
TI  - Comparative analysis of human, bovine, and murine Oct-4 upstream promoter
      sequences.
AB  - The Oct-4 gene encodes a transcription factor that is specifically expressed in
      embryonic stem cells and germ cells of the mouse embryo. Cells that differentiate
      into somatic tissues lose Oct-4 expression. Regulation of Oct-4 gene
      transcription involves a TATA-less minimal promoter and two upstream elements:
      the proximal (PE) and distal enhancers (DE). We report here the nucleotide
      sequence of the 5' upstream regulatory regions of the human and murine Oct-4
      genes. A comparative alignment analysis between these regions and those of the
      bovine Oct-4 ortholog reveals four conserved regions of homology (CR 1 to 4)
      between these species (66-94% conservation). The 1A sequence within the mouse PE
      is located approximately half-way between CR 2 and CR 3. A putative Sp1/Sp3
      binding site and the overlapping hormone responsive element (HRE) in CR1 are
      identical in all three species. A high number of CCC(A/T)CCC motifs exhibit
      various levels of homology in these upstream regions. We discuss the importance
      of these and other sequences and present candidate factors that may bind and
      regulate Oct-4 gene expression.

PMID- 11309665
TI  - Recombination is proportional to the number of chromosome arms in mammals.

PMID- 11309666
TI  - Transgenic rescue of the tattered phenotype by using a BAC encoding Ebp.

PMID- 11309667
TI  - Regional localization of 10 mariner transposon-like ESTs by means of FISH-
      evidence for a correlation with fragile sites.

PMID- 11309668
TI  - Is there a sex difference in human laterality? IV. An exhaustive survey of dual
      task interference studies from six neuropsychology journals.
AB  - The entire contents of six neuropsychology journals (161 volumes, 612 issues)
      were screened to identify dual-task laterality experiments. Of 112 experiments
      thus identified, 45.5% provided information about sex differences. Although 23
      experiments yielded at least one significant main effect or interaction involving
      the sex factor, only 5 outcomes represented an unambiguous sex difference in
      laterality. All 5 of those sex differences support the hypothesis of greater
      hemispheric specialization in males. The confirmatory outcomes constitute less
      than 10% of the informative experiments and less than 5% of the total population
      of experiments. These data alone do not rule out the possibility that sex
      differences are chance findings (Type I errors). However, when considered along
      with similar results from perceptual laterality data previously examined, the
      dual-task data fit the pattern of a small but reliable population-level sex
      difference in human laterality.

PMID- 11309669
TI  - Predictors of neuropsychological performance in HIV positive women.
AB  - This study examines predictors of neuropsychological (NP) performance in a
      community sample of 237 HIV seropositive and seronegative women. Consistent with
      literature describing the NP sequelae of HIV infection in men, we expected that
      HIV status would predict poorer NP performance on tests assessing verbal memory,
      psychomotor speed and motor speed. Multiple regression analyses testing the
      association between HIV serostatus and NP performance and controlling for
      predictors including age, ethnicity, education, psychological distress, and drug
      and alcohol use indicated that HIV serostatus was associated with slowed
      psychomotor speed. Specifically, AIDS diagnosis and HIV seropositivity predicted
      poorer performance on tests of psychomotor speed relative to HIV seronegatives.
      Contrary to expectations, no relationship between HIV serostatus and either motor
      speed or verbal memory performance emerged. Education, ethnicity, depressive
      distress, recent exposure to drugs as indexed by toxicology, and alcohol use were
      also associated with NP performance. Given that the HIV seropositive and
      seronegative samples differed on a number of demographic and drug use variables,
      a second series of analyses examining a subset of participants (matched on all
      key demographic factors) and with no illicit drug use during the past year was
      also conducted. Results of these analyses were similar to those obtained for the
      full sample, with AIDS diagnosis and HIV seropositivity predicting psychomotor
      slowing. To date, little work describing the NP sequelae of HIV infection in
      women has been conducted. This study provides one of the first descriptions of
      the NP effects of HIV/AIDS in a largely non-injection drug using community sample
      of women.

PMID- 11309670
TI  - Do subgroups of patients with Alzheimer's disease exhibit asymmetric deficits on
      memory tests?
AB  - Several studies have reported asymmetric cognitive profiles in patients with
      Alzheimer's disease (AD), but these results have almost exclusively been found
      using non-memory cognitive instruments. The present study investigated whether AD
      patients who display lateralized profiles on non-memory cognitive instruments
      also exhibit asymmetric deficits on verbal versus spatial memory tests. Sixty
      eight AD patients participated in the study: 36 with a "High Verbal" cognitive
      profile, and 32 with a "High Spatial" profile. The results indicated that the
      High Verbal AD patients performed significantly better than the High Spatial AD
      patients on verbal memory tests, but the two subgroups failed to differ on
      spatial memory tests. Implications of these findings for understanding the
      heterogeneous nature of cognitive profiles in AD patients are discussed.

PMID- 11309671
TI  - Confabulation and memory in patients with Alzheimer's disease.
AB  - Confabulation occurs in many brain diseases and concomitant with various
      cognitive disturbances. The purpose of the present study was to describe semantic
      features of confabulation and to investigate the relationship between these
      features and aspects of memory in Alzheimer's disease (AD). A group of 15 AD
      patients were asked questions aiming to evoke confabulations. The answers were
      analyzed with focus on semantic remoteness to the target answers into four
      different categories that made it possible to study the genesis of confabulation.
      Cognitive tests measuring episodic and semantic memory, priming as well as global
      cognitive functioning were performed, and the results were related to semantic
      features of confabulation. Results showed that semantic remoteness to the target
      answers was positively related to poor performance on Mini Mental State
      Examination but not to item recall, word fluency, or priming. It appears that
      difficulties with retrieval of recent autobiographical memories may have resulted
      in substitution of correct information with remote autobiographical memories,
      that is primary dysdeictic confabulations.

PMID- 11309672
TI  - Verbal learning and memory deficits in traumatic brain injury: encoding,
      consolidation, and retrieval.
AB  - The present study examined the nature of verbal memory deficits in individuals
      with traumatic brain injury (TBI) compared to healthy controls. The study was
      designed to control for methodological shortcomings of previous related research.
      Three groups of participants were used: (a) a head injured sample with moderate
      to severe traumatic brain injuries (N=55), (b) a control sample matched on age
      and initial performance on CVLT Trial 5 and Sum of Trials 1 to 5 (N=55), and (c)
      a control sample matched on age, education, and race, but not on initial CVLT
      learning performance (N=55). Current findings indicate that: (a) rate of learning
      was comparable across groups, consistent with no encoding differences, (b) TBI
      patients have a significantly more rapid rate of forgetting of new information
      than either acquisition-matched or demographic-matched controls, consistent with
      consolidation problems in TBI, (c) TBI patients have less proactive interference
      than demographic-matched control participants, consistent with a consolidation
      problem in the TBI group, (d) TBI patients and acquisition-matched controls have
      comparably low rates of proactive interference, consistent with impaired
      acquisition in both of these groups, and (e) TBI patients and controls do not
      differ in the benefit experienced from semantic or recognition retrieval cues,
      consistent with no differences in retrieval processes. These data support an
      impaired consolidation hypothesis, rather than encoding or retrieval deficits, as
      the primary deficit underlying memory impairment in TBI.

PMID- 11309673
TI  - Verbal recall and recognition following traumatic brain injury: a [0-15]-water
      positron emission tomography study.
AB  - Although several studies exist which have examined static functional neuroimaging
      following traumatic brain injury (TBI), controlled cognitive activation studies
      of episodic memory in this population have not been published. The present
      investigation studied verbal recall using [O-15]-water positron emission
      tomography (PET) in 5 individuals who sustained severe TBI (M GCS=6.8; M years
      post-injury=3.18), and 4 non-injured control participants. Statistical image
      analysis demonstrated changes in frontoparietal regional cerebral blood flow
      (rCBF) in both groups, but there were interesting differences between groups and
      across conditions. Frontal lobe rCBF changes in TBI patients were reduced during
      free recall but enhanced during recognition, when compared to controls. Changes
      in cerebellar rCBF were observed in the control group during free recall, but not
      in the TBI sample. In both groups, bifrontal rCBF increases were noted on
      recognition tasks. The present findings provide evidence of alterations in
      specific substrates involved in verbal recall following brain injury.

PMID- 11309674
TI  - Declarative and nondeclarative sequence learning tasks: closed-head injured
      patients versus control participants.
AB  - Patients who sustained closed-head injury (CHI) have been shown to have impaired
      memory for temporal order when measured under intentional, but not incidental,
      retrieval conditions. A group of 26 patients who sustained CHI and a matched
      control group of 26 individuals were tested on a declarative sequence learning
      task--"Chain Making" (CM), and a nondeclarative sequence learning task--Tower of
      Hanoi puzzle (TOHP). The TOHP is a problem solving task that requires planning
      and a strategic approach. The latter are cognitive processes known to be impaired
      following frontal lobe damage, as has been frequently documented in CHI patients.
      The goal of the present study was to test whether CHI patients' nondeclarative
      learning as measured by the TOHP task is preserved, as seen in amnesic patients,
      or impaired, as would be predicted following frontal lobe damage. Half of the
      participants in each group underwent active training, and the other half went
      through passive training of the tasks. The results demonstrate that the control
      group outperformed the CHI group (in most measures) in both declarative and
      nondeclarative sequence learning tasks. The effect of type of training differed
      for the two tasks: while performance of the control group on the TOHP was better
      under passive training (CHI patients did not improve on either one of the
      training modes), performance on the CM task was better under active training for
      both groups. The results are discussed in light of the role of the frontal lobes
      in memory generally, and in sequence learning particularly.

PMID- 11309675
TI  - The effects of event rate and signal probability on children's vigilance.
AB  - Using the study of vigilance in adults as their model, the researchers examined
      task parameters and their interactions in a study of sustained attention in
      children from a non-clinical population. Two levels of event rate (low and high)
      were combined with two levels of signal probability (low and high) in 14-minute
      vigilance tasks in which children viewed small and large squares presented
      successively on a computer screen. Seven- and eight-year-old children were
      instructed to press a button whenever a small square appeared. Signal detection
      analyses were employed, as well as the traditional measures identifying hits,
      false alarms, and reaction time. The results support the traditional findings in
      adult tasks: participants performed most accurately and quickly in the high event
      rate and high probability condition; low probability elicited a more conservative
      decision-making criterion, a standard characterized by less willingness to risk
      false alarms; such conservatism increased over the periods of watch; and the
      vigilance decrement emerged over time. However, the finding that the high event
      rate condition improved perceptual sensitivity reversed the event rate effect
      consistently reported in the adult literature. The above findings are discussed
      in light of both research and clinical implications.

PMID- 11309676
TI  - Supervisory attentional system in patients with focal frontal lesions.
AB  - The aim of this study was to re-examine the hypothesis of a link between frontal
      cortex and the Supervisory Attentional System (SAS; Shallice, 1988). Contrary to
      previous studies that examined patients with lesions extending beyond the frontal
      lobes (Shallice, 1982; Burgess & Shallice, 1996a, 1996b), SAS or executive
      functions were evaluated in a group of patients with strict frontal lesions.
      Three tasks (Tower of London -TOL-, Hayling and Brixton tests) designed to assess
      specific SAS processes (planning, inhibition and abstraction of logical rules
      respectively) were administered. In the TOL test, although frontal patients were
      slower than control participants, the two groups did not differ in their ability
      to solve problems. Furthermore, the two groups did not differ in terms of
      performance in the Hayling and Brixton tests either. These results are discussed
      in terms of the SAS model and are compared to those observed by Shallice (1982)
      and Burgess & Shallice (1996a, 1996b). Additionally, the issue of the neural
      subtract of executive functions is addressed.

PMID- 11309677
TI  - Cognitive functioning in Gulf War Illness.
AB  - A comprehensive neuropsychological battery was administered to 48 veterans with
      Gulf War Illness (GWI) characterized by severe fatigue (GV-F) and 39 healthy
      veterans (GV-H). Subjects were matched on intelligence and did not differ on age,
      gender, race, and alcohol consumption. Compared to GVs-H, GVs-F were
      significantly impaired on four tasks: three attention, concentration, information
      processing tasks and one measure of abstraction and conceptualization. After
      considering the presence of post-war Axis I psychopathology, GWI remained a
      significant predictor of cognitive performance on one of the attention,
      concentration, and information processing tasks and one abstraction and
      conceptualization measure. Performance on the remaining two attention,
      concentration, and information processing tasks was only significantly predicted
      by Axis I psychopathology with post-war onset. The results suggest that Gulf War
      Illness is associated with some aspects of cognitive dysfunction in Gulf
      Veterans, over and above the contribution of psychopathology.

PMID- 11309678
TI  - Identification and expression analysis of spastin gene mutations in hereditary
      spastic paraplegia.
AB  - Pure hereditary spastic paraplegia (SPG) type 4 is the most common form of
      autosomal dominant hereditary SPG, a neurodegenerative disease characterized
      primarily by hyperreflexia and progressive spasticity of the lower limbs. It is
      caused by mutations in the gene encoding spastin, a member of the AAA family of
      ATPases. We have screened the spastin gene for mutations in 15 families
      consistent with linkage to the spastin gene locus, SPG4, and have identified 11
      mutations, 10 of which are novel. Five of the mutations identified are in
      noninvariant splice-junction sequences. Reverse transcription-PCR analysis of
      mRNA from patients shows that each of these five mutations results in aberrant
      splicing. One mutation was found to be "leaky," or partially penetrant; that is,
      the mutant allele produced both mutant (skipped exon) and wild-type (full-length)
      transcripts. This phenomenon was reproduced in in vitro splicing experiments,
      with a minigene splicing-vector construct only in the context of the endogenous
      splice junctions flanking the splice junctions of the skipped exon. In the
      absence of endogenous splice junctions, only mutant transcript was detected. The
      existence of at least one leaky mutation suggests that relatively small
      differences in the level of wild-type spastin expression can have significant
      functional consequences. This may account, at least in part, for the wide ranges
      in age at onset, symptom severity, and rate of symptom progression that have been
      reported to occur both among and within families with SPG linked to SPG4. In
      addition, these results suggest caution in the interpretation of data solely
      obtained with minigene constructs to study the effects of sequence variation on
      splicing. The lack of full genomic sequence context in these constructs can mask
      important functional consequences of the mutation.

PMID- 11309679
TI  - MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of
      paternal origin.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that apparently is
      lethal in male embryos. RTT almost exclusively affects female offspring and, in
      99.5% of all cases, is sporadic and due to de novo mutations in the MECP2 gene.
      Familial cases of RTT are rare and are due to X-chromosomal inheritance from a
      carrier mother. We analyzed the parental origin of MECP2 mutations in sporadic
      cases of RTT, by analysis of linkage between the mutation in the MECP2 gene and
      intronic polymorphisms in 27 families with 15 different mutations, and we found a
      high predominance of mutations of paternal origin in 26 of 27 cases (P<.001). The
      paternal origin was independent of type of mutation and was found for single-base
      exchanges as well as for deletions. Parents were not of especially advanced age.
      We conclude that de novo mutations in RTT occur almost exclusively on the
      paternally derived X chromosome and that this is most probably the cause for the
      high female:male ratio observed in patients with RTT. Affected males recently
      have been described in a few cases of familial inheritance. Identification of the
      parental origin may be useful to distinguish between the sporadic form of RTT and
      a potentially familial form. This distinction will allow geneticists to offer
      more-specific counseling and discriminate between higher (maternal origin) and
      lower (paternal origin) recurrence risk.

PMID- 11309680
TI  - Identification of a new candidate locus for uric acid nephrolithiasis.
AB  - Renal stone formation is a common multifactorial disorder, of unknown etiology,
      with an established genetic contribution. Lifetime risk for nephrolithiasis is
      approximately 10% in Western populations, and uric acid stones account for 5%-10%
      of all stones, depending on climatic, dietary, and ethnic differences. We studied
      a small, isolated founder population in Sardinia, characterized by an increased
      prevalence of uric acid stones, and performed a genomewide search in a deep
      rooted pedigree comprising many members who formed uric acid renal stones. The
      pedigree was created by tracing common ancestors of affected individuals through
      a genealogical database based on archival records kept by the parish church since
      1640. This genealogical information was used as the basis for the study strategy,
      involving screening for alleles shared among affected individuals, originating
      from common ancestors, and utilization of large pedigrees to obtain greater power
      for linkage detection. We performed multistep linkage and allele-sharing
      analyses. In the initial stage, 382 markers were typed in 14 closely related
      affected subjects; interesting regions were subsequently investigated in the
      whole sample. We identified two chromosomal regions that may harbor loci with
      susceptibility genes for uric acid stones. The strongest evidence was observed on
      10q21-q22, where a LOD score of 3.07 was obtained for D10S1652 under an affected
      only dominant model, and a LOD score of 3.90 was obtained using a dominant
      pseudomarker assignment. The localization was supported also by multipoint allele
      sharing statistics and by haplotype analysis of familial cases and of unrelated
      affected subjects collected from the isolate. In the second region on 20q13.1
      13.3, multipoint nonparametric scores yielded suggestive evidence in a
      approximately 20-cM region, and further analysis is needed to confirm and fine
      map this putative locus. Replication studies are required to investigate the
      involvement of these regions in the genetic contribution to uric acid stone
      formation.

PMID- 11309681
TI  - Characterization of mutations in the CPO gene in British patients demonstrates
      absence of genotype-phenotype correlation and identifies relationship between
      hereditary coproporphyria and harderoporphyria.
AB  - Hereditary coproporphyria (HCP) is the least common of the autosomal dominant
      acute hepatic porphyrias. It results from mutations in the CPO gene that encodes
      the mitochondrial enzyme, coproporphyrinogen oxidase. A few patients have also
      been reported who are homoallellic or heteroallelic for CPO mutations and are
      clinically distinct from those with HCP. In such patients the presence of a
      specific mutation (K404E) on one or both alleles produces a neonatal hemolytic
      anemia that is known as "harderoporphyria"; mutations on both alleles elsewhere
      in the gene give rise to the "homozygous" variant of HCP. The molecular
      relationship between these disorders and HCP has not been defined. We describe
      the molecular investigation and clinical features of 17 unrelated British
      patients with HCP. Ten novel and four previously reported CPO mutations, together
      with three previously unrecognized single-nucleotide polymorphisms, were
      identified in 15 of the 17 patients. HCP is more heterogeneous than other acute
      porphyrias, with all but one mutation being restricted to a single family, with a
      predominance of missense mutations (10 missense, 2 nonsense, 1 frameshift, and 1
      splice site). Of the four known mutations, one (R331W) has previously been
      reported to cause disease only in homozygotes. Heterologous expression of another
      mutation (R401W) demonstrated functional properties similar to those of the K404E
      harderoporphyria mutation. In all patients, clinical presentation was uniform, in
      spite of the wide range (1%-64%) of residual coproporphyrinogen oxidase activity,
      as determined by heterologous expression. Our findings add substantially to
      knowledge of the molecular epidemiology of HCP, show that single copies of CPO
      mutations that are known or predicted to cause "homozygous" HCP or
      harderoporphyria can produce typical HCP in adults, and demonstrate that the
      severity of the phenotype does not correlate with the degree of inactivation by
      mutation of coproporphyrinogen oxidase.

PMID- 11309682
TI  - International collaboration provides convincing linkage replication in complex
      disease through analysis of a large pooled data set: Crohn disease and chromosome
      16.
AB  - Numerous familial, non-Mendelian (i.e., complex) diseases have been screened by
      linkage analysis for regions harboring susceptibility genes. Except for rare,
      high-penetrance syndromes showing Mendelian inheritance, such as BRCA1 and BRCA2,
      most attempts have failed to produce replicable linkage findings. For example, in
      multiple sclerosis and other complex diseases, there have been many reports of
      significant linkage, followed by numerous failures to replicate. In inflammatory
      bowel disease (IBD), linkage to two regions has elsewhere been reported at
      genomewide significance levels: the pericentromeric region on chromosome 16
      (IBD1) and chromosome 12q (IBD2). As with other complex diseases, the subsequent
      support for these localizations has been variable. In this article, we report the
      results of an international collaborative effort to investigate these putative
      localization by pooling of data sets that do not individually provide convincing
      evidence for linkage to these regions. Our results, generated by the genotyping
      and analysis of 12 microsatellite markers in 613 families, provide unequivocal
      replication of linkage for a common human disease: a Crohn disease susceptibility
      locus on chromosome 16 (maximum LOD score 5.79). Despite failure to replicate the
      previous evidence for linkage on chromosome 12, the results described herein
      indicate the need to further investigate the potential role of this locus in
      susceptibility to ulcerative colitis. This report provides a convincing example
      of the collaborative approach necessary to obtain the sample numbers required to
      achieve statistical power in studies of complex human traits.

PMID- 11309684
TI  - Regression models for linkage heterogeneity applied to familial prostate cancer.
AB  - Linkage heterogeneity frequently occurs for complex genetic diseases, and
      statistical methods must account for it to avoid severe loss in power to discover
      susceptibility genes. A common method to allow for only a fraction of linked
      pedigrees is to fit a mixture likelihood and then to test for linkage
      homogeneity, given linkage (admixture test), or to test for linkage while
      allowing for heterogeneity, using the heterogeneity LOD (HLOD) score.
      Furthermore, features of the families, such as mean age at diagnosis, may help to
      discriminate families that demonstrate linkage from those that do not. Pedigree
      features are often used to create homogeneous subsets, and LOD or HLOD scores are
      then computed within the subsets. However, this practice introduces several
      problems, including reduced power (which results from multiple testing and small
      sample sizes within subsets) and difficulty in interpretation of results. To
      address some of these limitations, we present a regression-based extension of the
      mixture likelihood for which pedigree features are used as covariates that
      determine the probability that a family is the linked type. Some advantages of
      this approach are that multiple covariates can be used (including quantitative
      covariates), covariates can be adjusted for each other, and interactions among
      covariates can be assessed. This new regression method is applied to linkage data
      for familial prostate cancer and provides new insights into the understanding of
      prostate cancer linkage heterogeneity.

PMID- 11309683
TI  - Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing
      familial hypercholesterolemia: positive selection is not always necessary to
      account for disease incidence among Ashkenazi Jews.
AB  - G197del is the most prevalent LDL receptor (LDLR) mutation causing familial
      hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this
      study was to determine the origin, age, and population distribution of G197del,
      as well as to explore environmental and genetic effects on disease expression.
      Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The
      Netherlands (n=1), and the United States (n=1) were enlisted. All trace their
      ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208
      D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a
      common founder. When two methods were used for analysis of linkage disequilibrium
      (LD) between flanking polymorphic markers and the disease locus and for the study
      of the decay of LD over time, the estimated age of the deletion was found to be
      20 +/- 7 generations (the 95% confidence interval is 15-26 generations), so that
      the most recent common ancestor of the mutation-bearing chromosomes would date to
      the 14th century. This corresponds with the founding of the Jewish community of
      Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ
      individuals in eastern Europe, which followed this settlement. The penetrance of
      mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a
      baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no
      significant differences in the mean baseline lipid level of G197del carriers from
      different countries were found. Polymorphisms of apolipoprotein E and of
      scavenger-receptor class B type I were observed to have minor effects on the
      plasma lipid profile. With respect to determinative genetic influences on the
      biochemical phenotype, there is no evidence that could support the possibility of
      a selective evolutionary metabolic advantage. Therefore, the founder effect in a
      rapidly expanding population from a limited number of families remains a simple,
      parsimonious hypothesis explaining the spread of G197del-LDLR-linked FH in AJ
      individuals.

PMID- 11309685
TI  - Model-free linkage analysis with covariates confirms linkage of prostate cancer
      to chromosomes 1 and 4.
AB  - As with many complex genetic diseases, genome scans for prostate cancer have
      given conflicting results, often failing to provide replication of previous
      findings. One factor contributing to the lack of consistency across studies is
      locus heterogeneity, which can weaken or even eliminate evidence for linkage that
      is present only in a subset of families. Currently, most analyses either fail to
      account for locus heterogeneity or attempt to account for it only by partitioning
      data sets into smaller and smaller portions. In the present study, we model locus
      heterogeneity among affected sib pairs with prostate cancer by including
      covariates in the linkage analysis that serve as surrogate measures of between
      family linkage differences. The model is a modification of the Olson conditional
      logistic model for affected relative pairs. By including Gleason score, age at
      onset, male-to-male transmission, and/or number of affected first-degree family
      members as covariates, we detected linkage near three locations that were
      previously identified by linkage (1q24-25 [HPC1; LOD score 3.25, P=.00012],
      1q42.2-43 [PCAP; LOD score 2.84, P=.0030], and 4q [LOD score 2.80, P=.00038]),
      near the androgen-receptor locus on Xq12-13 (AR; LOD score 3.06, P=.00053), and
      at five new locations (LOD score > 2.5). Without covariates, only a few weak-to
      moderate linkage signals were found, none of which replicate findings of previous
      genome scans. We conclude that covariate-based linkage analysis greatly improves
      the likelihood that linked regions will be found by incorporation of information
      about heterogeneity within the sample.

PMID- 11309687
TI  - A confidence-set approach for finding tightly linked genomic regions.
AB  - As more studies adopt the approach of whole-genome screening, geneticists are
      faced with the challenge of having to interpret results from traditional
      approaches that were not designed for genome-scan data. Frequently, two-point
      analysis by the LOD method is performed to search for signals of linkage
      throughout the genome, for each of hundreds or even thousands of markers. This
      practice has raised the question of how to adjust the significance level for the
      fact that multiple tests are being performed. Various recommendations have been
      made, but no consensus has emerged. In this article, we propose a new method, the
      confidence-set approach, that circumvents the need to correct for the level of
      significance according to the number of markers tested. In the search for the
      gene location of a monogenic disorder, multiplicity adjustment is not needed in
      order to maintain the desired level of confidence. For complex diseases involving
      multiple genes, one needs only to adjust the level of significance according to
      the number of disease genes--a much smaller number than the number of markers in
      a genome screen-to ensure a predetermined genomewide confidence level.
      Furthermore, our formulation of the tests enables us to localize disease genes to
      small genomic regions, an extremely desirable feature that the traditional LOD
      method lacks. Our simulation study shows that, for sib-pair data, even when the
      coverage probability of the confidence set is chosen to be as high as 99%, our
      approach is able to implicate only the markers that are closely linked to the
      disease genes.

PMID- 11309686
TI  - Segregation analyses of 1,476 population-based Australian families affected by
      prostate cancer.
AB  - Segregation analyses aim to detect genetic factors that have a major effect on an
      individual's risk of disease and to describe them in terms of mode of
      inheritance, age-specific cumulative risk (penetrance), and allele frequency. We
      conducted single- and two-locus segregation analyses of data from 1,476 men with
      prostate cancer diagnosed at age <70 years and ascertained through population
      registries in Melbourne, Sydney, and Perth, Australia, and from their brothers,
      fathers, and both maternal and paternal lineal uncles. Estimation and model
      selection were based on asymptotic likelihood theory and were performed through
      use of the software MENDEL. All two-locus models gave better fits than did single
      locus models, even if lineal uncles were excluded or if we censored data (age and
      disease status) for relatives at 1992, when prostate-specific-antigen testing
      started to have a major impact on the incidence of prostate cancer in Australia.
      Among the genetic models that we considered, the best-fitting ones included a
      dominantly inherited increased risk that was greater, in multiplicative terms, at
      younger ages, as well as a recessively inherited or X-linked increased risk that
      was greater, in multiplicative terms, at older ages. The recessive and X-linked
      effects were strongly confounded, and it was not possible to fit them together.
      Penetrance to age 80 years was approximately 70% (95% confidence interval [CI]
      57%-85%) for the dominant effect and virtually 100% for the recessive and X
      linked effects. Approximately 1/30 (95% CI 1/80-1/12) men would carry the
      dominant risk, and 1/140 (95% CI 1/220-1/90) would carry the recessive risk or
      1/200 (95% CI 1/380-1/100) would carry the X-linked risk. Within discussed
      limitations, these analyses confirm the genetic heterogeneity, of prostate cancer
      susceptibility, that is becoming evident from linkage analyses, and they may aid
      future efforts in gene discovery.

PMID- 11309688
TI  - Transformation of sib-pair values for the Haseman-Elston method.
AB  - The squared sib-pair phenotype difference (SQD) has been used as a dependent
      variable in the Haseman-Elston (H-E) regression quantitative-trait locus (QTL)
      linkage method, but it has been shown that the SQD does not make full use of
      linkage information. In this study, we examine the efficiency of SQD in H-E
      regression compared to other proposed functions of the sib-pair phenotypes. A new
      function of sib-pair phenotypes, the product of pair values corrected with family
      mean (PCF), is shown to have desirable properties in many realistic situations.
      Consistent results were obtained using a combination of large-sample analytic
      approximations, simulation, and analyses of quantitative-trait data from Genetic
      Analysis Workshop 10. The advantages of PCF are further improved in the presence
      of family-specific effects arising from environmental factors or when additional
      QTLs influence the trait. All of the phenotype functions are incorporated in our
      new, freely available linkage-mapping program MULTIGENE 1.0 for the PC
      environment.

PMID- 11309689
TI  - Transmission/disequilibrium test meets measured haplotype analysis: family-based
      association analysis guided by evolution of haplotypes.
AB  - Family data teamed with the transmission/disequilibrium test (TDT), which
      simultaneously evaluates linkage and association, is a powerful means of
      detecting disease-liability alleles. To increase the information provided by the
      test, various researchers have proposed TDT-based methods for haplotype
      transmission. Haplotypes indeed produce more-definitive transmissions than do the
      alleles comprising them, and this tends to increase power. However, the larger
      number of haplotypes, relative to alleles at individual loci, tends to decrease
      power, because of the additional degrees of freedom required for the test. An
      optimal strategy would focus the test on particular haplotypes or groups of
      haplotypes. In this report we develop such an approach by combining the theory of
      TDT with that of measured haplotype analysis (MHA). MHA uses the evolutionary
      relationships among haplotypes to produce a limited set of hypothesis tests and
      to increase the interpretability of these tests. The theory of our approach,
      called the "evolutionary tree" (ET)-TDT, is developed for two cases: when
      haplotype transmission is certain and when it is not. Simulations show the ET-TDT
      can be more powerful than other proposed methods under reasonable conditions.
      More importantly, our results show that, when multiple polymorphisms are found
      within the gene, the ET-TDT can be useful for determining which polymorphisms
      affect liability.

PMID- 11309690
TI  - Broad and narrow heritabilities of quantitative traits in a founder population.
AB  - Estimation of the components of variance for a quantitative trait allows one to
      evaluate both the degree to which genetics influences the trait and the trait's
      underlying genetic architecture. For particular traits, the estimates also may
      have implications for discriminating between potential models of selection and
      for choosing an appropriate model for linkage analysis. Using a recently
      developed method, we estimate the additive and dominance components of variance-
      or, equivalently, the narrow and broad sense heritabilities--of several traits in
      the Hutterites, a founder population with extensive genealogical records. As a
      result of inbreeding and because Hutterite individuals are typically related
      through multiple lines of descent, we expect that power to detect dominance
      variance will be increased relative to that in outbred studies. Furthermore, the
      communal lifestyle of the Hutterites allows us to evaluate the genetic influences
      in a relatively homogeneous environment. Four phenotypes had a significant
      dominance variance, resulting in a relatively high broad heritability. We
      estimated the narrow and broad heritabilities as being, respectively,.36 and.96
      for LDL,.51 and 1.0 for serotonin levels, and.45 and.76 for fat free mass (FFM).
      There was no significant additive component for systolic blood pressure (SBP),
      resulting in a narrow heritability of 0 and a broad heritability of.45. There
      were several traits for which we found no significant dominance component,
      resulting in equal broad and narrow heritability estimates. These traits and
      their heritabilities are as follows: HDL,.63; triglycerides,.37; diastolic blood
      pressure,.21; immunoglobulin E,.63; lipoprotein(a),.77; and body-mass index,.54.
      The large difference between broad and narrow heritabilities for LDL, serotonin,
      FFM, and SBP are indicative of strong dominance effects in these phenotypes. To
      our knowledge, this is the first study to report an estimate of heritability for
      serotonin and to detect a dominance variance for LDL, FFM, and SBP.

PMID- 11309691
TI  - Introduction to flow cytometry.

PMID- 11309692
TI  - Immunophenotyping.
AB  - Immunophenotyping of leukocytes for nonmalignant conditions uses the power of
      multiparameter flow cytometry to count specific lymphocyte populations and
      evaluate the presence or absence of particular cell surface markers. Its main
      clinical indications, and the focus of this chapter, are enumeration of CD4 T
      cell counts and activation markers on T cells in human immunodeficiency virus
      (HIV) infection, immunophenotypic characterization of primary immunodeficiency
      disorders and immune-mediated diseases, and the study of immune reconstitution
      following stem cell transplantation (SCT). Immunophenotyping has advanced our
      understanding of many immunologic disorders, which in turn have stimulated new
      developments in the field of flow cytometry, such as quantitative flow cytometry
      and single-platform technology. Semin Hematol 38:100-110. This is a US government
      work. There are no restrictions on its use.

PMID- 11309693
TI  - Flow cytometric analysis of lymphomas and lymphoproliferative disorders.
AB  - Flow cytometry has become an important tool in the diagnosis and characterization
      of hematologic and lymphoid neoplasia. This technology serves as an excellent
      complement to microscope-based traditional diagnostic methods and adds
      distinctive capabilities that are unmatched by any other diagnostic methods. Flow
      cytometry is ideal for fluids where cells are naturally suspended but is also
      useful in lymphoid tissues, from which single-cell suspensions can be easily
      obtained. The advantages of flow cytometry are largely based on its ability to
      analyze very rapidly, even in small samples, multiple cell properties
      simultaneously, including size, granularity, surface and intracellular antigens,
      and DNA content. The quantitative nature of the data produced, both with regard
      to cell population distributions and to expression of individual cell antigens,
      offers objective criteria for interpretation of results. Examples of applications
      include the detection of clonal cells in B-cell lymphoma, the recognition of
      antigenic expression anomalies in B- or T-cell malignancies, the identification
      of malignant plasma cells, and the rapid measurement of cell cycle fractions. The
      unique attributes of flow cytometry allow for increased sensitivity in the
      detection of neoplastic cells and should contribute to improving accuracy and
      precision in the diagnosis and classification of lymphomas and
      lymphoproliferative disorders. Semin Hematol 38:111-123. This is a US government
      work. There no restrictions on its use.

PMID- 11309694
TI  - Flow cytometry in the diagnosis of acute leukemia.
AB  - Acute leukemias are a heterogeneous group of malignancies with varying clinical,
      morphologic, immunologic, and molecular characteristics. Many distinct types are
      known to carry predictable prognoses and warrant specific therapy. Distinction
      between lymphoid and myeloid leukemias, most often made by flow cytometry, is
      crucially important. Several advances in flow cytometry, including availability
      of new monoclonal antibodies, improved gating strategies, and multiparameter
      analytic techniques, have all dramatically improved the utility of flow cytometry
      in the diagnosis and classification of leukemia. Acute leukemias reflect the
      pattern of antigen acquisition seen in normal hematopoietic differentiation, yet
      invariably demonstrate distinct aberrant immunophenotypic features. Detailed
      understanding of these phenotypic patterns of differentiation, particularly in
      myeloid leukemia, allows for more precise classification of leukemia than does
      morphology alone. However, morphologic and differentiation-based classifications
      of leukemia are limited in their prognostic value; cytogenetics and molecular
      genetics appear to be most important for identifying entities with distinct
      prognoses and clinical behavior. Increasingly, many of these genetically distinct
      subgroups of leukemia have been found to be closely associated with distinct
      immunophenotypes. For example, translocations such as t(8;21), t(15;17), and
      inv(16) in acute myeloid leukemia (AML), and t(1;19) and t(12;21) in acute
      lymphoblastic leukemia (ALL) have distinctive immunophenotypic profiles. Thus, in
      addition to classification into differentiation-based subtypes, detailed flow
      cytometric studies can define complex antigenic profiles that are associated with
      specific molecular defects and well-defined biology. In summary, multiparameter
      flow cytometry is an invaluable tool in the diagnosis, classification, and
      monitoring of patients with acute leukemia. Semin Hematol 38:124-138.

PMID- 11309695
TI  - Flow cytometric enumeration and immunophenotyping of hematopoietic stem and
      progenitor cells.
AB  - Flow cytometric enumeration of CD34(+) hematopoietic stem and progenitor cells
      (HPC) is widely used to evaluate the adequacy of peripheral blood stem cell
      grafts and is also useful for planning the apheresis sessions needed to obtain
      these grafts. A state-of-the-art method to enumerate CD34(+) cells has been
      developed that makes use of a multiparameter definition of HPC, based on their
      light scatter characteristics and dim expression of CD45, utilizing fluorescent
      counting beads. This approach allows the absolute CD34(+) cell count to be
      determined directly from a flow cytometer. The method can be extended with a
      viability stain and additional markers for further immunologic characterization
      of CD34(+) cells, and has been successfully implemented in multicenter trials.
      Using such a standardized assay, it should be possible to define more accurately
      the lower threshold for a safe HPC graft in terms of short- and long-term
      hematopoietic reconstitution. Semin Hematol 38:139-147.

PMID- 11309696
TI  - Diagnostic advances in defining erythropoietic abnormalities and red blood cell
      diseases.
AB  - The majority of clinical applications of flow cytometry begin with various
      approaches to remove red blood cells (RBCs) from the clinical sample. However,
      multiparameter cytometry has and will continue to contribute much to the
      understanding of the pathophysiology and diagnostic accuracy in the clinical
      evaluation of human diseases affecting erythroid cells. This review summarizes
      the diagnostic advances relating to erythroid cells in the areas of
      immunohematology, laboratory hematology, and infectious disease with particular
      emphasis on medical evaluation of the anemic patient and fetomaternal hemorrhage.
      Semin Hematol 38:148-159.

PMID- 11309697
TI  - The clinical utility of flow cytometry in the study of platelets.
AB  - Flow cytometry has emerged in the past few years as an important technology for
      the study of platelets. It offers the ability to make measurements on platelets
      with little or no isolation or manipulation. Most flow cytometric platelet
      studies can be carried out on whole blood, thus eliminating a host of artifacts.
      In addition, flow cytometric techniques have been developed that allow the
      measurement of nearly all of the functional capabilities of platelets, such as
      activation and aggregation and to identify new functions by permitting
      observation of platelets interacting with leukocytes and measurement of platelet
      microparticles. Several of these measurements have already reached the stage of
      clinical utility and others offer considerable promise for practical
      applications. This review describes each of the flow cytometric techniques used
      to study platelets and summarizes their current state of clinical utility. Semin
      Hematol 38:160-168.

PMID- 11309698
TI  - Cell function-based flow cytometry.
AB  - Flow cytometry is increasingly used to assess the functional status of
      leukocytes, and practically all aspects of their life (and death) are accessible
      to flow cytometric study. Together with familiar features of flow cytometry, such
      as multiparameter immunophenotyping, cell function-based flow cytometry has
      provided many new insights into the relationships among lymphocyte cell surface
      features; intracellular processes, such as cytokine production and protein
      phosphorylation; and the functional status of lymphocytes in a variety of human
      diseases. Direct visualization and quantification of antigen-specific T cells
      using major histocompatibility complex (MHC)-peptide tetramer technology, in
      combination with functional assays, has provided the means to study specific T
      cell subsets of interest. Even early in its development, this technology already
      has offered a better understanding of basic and clinical immunology and has
      invited reassessment of several long-standing immunologic concepts. Semin Hematol
      38:169-178. This is a US government work. There are no restrictions on its use.

PMID- 11309699
TI  - Flow cytometry in analysis of cell cycle and apoptosis.
AB  - The capacity for multiparametric measurement of large cell populations rapidly
      and accurately offered by cytometry has made this methodology indispensable in
      studies of cell proliferation and cell death. The reviewed cell cycle
      applications include (1) the univariate analysis of cellular DNA content for
      identification of G(0/1) versus S versus G(2)/M cells; (2) discrimination between
      noncycling (G(0); quiescent) and proliferating cells, based on the presence of
      proliferation-associated proteins; (3) identification of mitotic cells by histone
      H3 phosphorylation; (4) bivariate analysis of expression of cyclins D, E, A, or
      B1 versus DNA content; and (5) detection of DNA replicating cells and analysis of
      cell kinetics from the bivariate distributions of 5-bromo-2'-deoxyuridine (BrdU)
      incorporation versus DNA content. For the identification of apoptotic cells and
      discrimination between apoptosis and necrosis, flow cytometry techniques are
      applied to evaluate for changes in cell morphology, the presence of
      phosphatidylserine on cell surface, collapse of mitochondrial transmembrane
      potential, DNA fragmentation, and evidence of caspase activation. Semin Hematol
      38:179-193.

PMID- 11309700
TI  - Flow cytometry in human leukocyte antigen testing.
AB  - Stem cell transplantation is a recognized treatment for many hematologic
      malignancies. Human leukocyte antigen (HLA) testing is a key assessment in the
      evaluation of potential recipients and selection of the appropriate stem cell
      donor. Over the past several years, technological advances have moved HLA testing
      from a serologic art form to a sophisticated and high-resolution molecular-based
      procedure. HLA typing is now performed by DNA-based methods, while flow cytometry
      has significantly improved our ability to detect HLA antibodies. Although DNA
      based typing methods have advanced our understanding of HLA polymorphisms, HLA
      antibodies still play a role in both stem cell and solid organ transplantation
      and can lead to failed engraftment or allograft graft rejection, respectively.
      Flow cytometric crossmatching and HLA antigen-specific microparticle assays
      represent the new HLA serology. Together, these new technologies are impacting
      patient outcomes and are expanding our understanding of the immune response to
      HLA alloantigens. Semin Hematol 38:194-200.

PMID- 11309701
TI  - The epidemiology of multiple myeloma.
AB  - Increases in the incidence of multiple myeloma during this past century implicate
      environmental factors as important causal agents. The molecular and cytogenetic
      alterations in multiple myeloma are under investigation, but the precise causes
      of these abnormalities are largely unknown. Exposure to chemical substances and
      ionizing radiation are associated with an increased risk of multiple myeloma. A
      single insult is probably not sufficient to induce the disease, which results
      from the clonal expansion of an idiotypic plasma cell after cumulative mutational
      damage has altered its genetic makeup. Multiple myeloma does not have the same
      biology in all patients; it is best viewed as a heterogeneous disease with a
      different prognosis, clinical course, and response to therapeutic interventions
      in different subjects. Full details of the genetic background in a given patient
      are required to better understand the disease. Hopefully this information will be
      available soon, using DNA array and related technologies.

PMID- 11309703
TI  - Multiple Myeloma. Diagnostic challenges and standard therapy.
AB  - In the diagnosis of multiple myeloma (MM), the clinician must exclude other
      disorders in which a plasma cell reaction may occur such as rheumatoid arthritis
      and connective tissue disorders, or metastatic carcinoma where the patient may
      have osteolytic lesions associated with bone metastases. Patients with smoldering
      multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance
      (MGUS) have none of the complicating features of MM and do not require treatment
      with potentially toxic agents. The plasma cell labeling index can help make a
      differential diagnosis of MM from SMM. Patients with a high labeling index have a
      high risk of complications and should be monitored carefully. However, the
      labeling index can be low in active MM. In addition, SMM or MGUS patients have
      few or no circulating plasma cells. High-dose chemotherapy and stem cell support
      prolong overall survival in contrast to conventional therapy. If stem cell
      transplantation is considered, it is important to harvest the cells before using
      alkylating agents to obtain a sufficient number of cells. Supportive treatment
      consists of the occasional use of erythropoietin to maintain adequate hemoglobin
      levels and adequate hydration to protect renal function. Vaccination against
      pneumococcal infections and the prophylactic use of antibiotic therapy during the
      first 2 months of treatment can be beneficial. Recognizing the symptoms of spinal
      cord compression and initiating dexamethasone therapy promptly to prevent
      paraplegia are critical.

PMID- 11309702
TI  - Multiple Myeloma. Advances in disease biology: therapeutic implications.
AB  - The survival and proliferation of multiple myeloma cells are largely dependent on
      a supportive microenvironment. Interleukin-6 (IL-6) is known for its ability to
      support cell growth and prevent apoptosis, and clinical trials using monoclonal
      antibodies to block IL-6 or its receptors are underway. Apoptosis of myeloma
      cells triggered by corticosteroids is mediated by related focal adhesion tyrosine
      kinase (RAFTK); blocking RAFTK inhibits this apoptosis-inducing effect IL-6
      activates SHP2, which inhibits RAFTK activation, thereby protecting multiple
      myeloma cells from the apoptotic effects of corticosteroids. Therefore, SHP2 and
      RAFTK might be appropriate targets for therapeutic interventions in multiple
      myeloma. Angiogenesis is also prominent in the pathogenesis of multiple myeloma.
      Vascular endothelial growth factor (VEGF) is one of the important endogenous
      factors that promote angiogenesis. An understanding of the process of
      angiogenesis in myeloma is necessary, because its inhibition offers promising
      prognostic and therapeutic implications. Thalidomide has recently been found to
      have both antiangiogenic and immunostimulating effects, and may be an important
      new antimyeloma agent. Immune-based therapies will likely play an increasing role
      in the treatment of multiple myeloma, and novel approaches are directed to
      generating immune responses to specific multiple myeloma antigens.

PMID- 11309704
TI  - New advances in the biology and treatment of myeloma bone disease.
AB  - The bisphosphonates provide effective therapy for the skeletal complications of
      multiple myeloma (MM). Although the earliest bisphosphonates had poor
      bioavailability and relatively low potency, newer compounds such as pamidronate
      and zoledronic acid have greater potency. Bisphosphonates block the development
      of monocytes into osteoclasts and are thought to promote apoptosis of
      osteoclasts. These agents prevent osteoclasts from moving to the bone surface and
      seem to inhibit the production of bone-resorbing cytokines such as interleukin-6
      (IL-6) by bone marrow stromal cells. In addition, bisphosphonates seem to have a
      direct antimyeloma effect by inducing apoptosis of malignant plasma cells. The
      beneficial effects of pamidronate have been demonstrated in a clinical trial
      setting. Patients who failed to respond to chemotherapy had a slight prolongation
      of survival and better performance status and quality of life. Ongoing clinical
      trials with ibandronate and zoledronic acid indicate the latter is 100 to 1,000
      times more potent than pamidronate. Biochemical effects of zoledronic acid
      continue for as long as 8 weeks after a single administration. In a new trial
      comparing pamidronate and zoledronic acid, 90% of the patients who received
      zoledronic acid were normocalcemic, compared with 69% of those who received
      pamidronate at 10 days. In addition, the time to relapse or development of
      hypercalcemia was shorter for patients receiving pamidronate compared with
      zoledronic acid.

PMID- 11309705
TI  - High-dose therapy and innovative approaches to treatment of multiple myeloma.
AB  - High-dose therapy in multiple myeloma (MM) appears to be superior in terms of
      event-free survival and overall survival compared with conventional therapy.
      Melphalan-based high-dose therapy increases complete remission rates from 5% to
      50% and extends event-free survival beyond 3 years and overall survival beyond 6
      years. Critical disease features associated with durable complete remission,
      event-free survival, and overall survival include the absence of chromosome 13
      deletion, low beta(2)-microglobulin, and low C-reactive protein levels. Data on
      1,000 patients enrolled in tandem high-dose trials show that chromosome 13
      deletion is an important prognostic feature. The timely application of a second
      cycle of high-dose therapy extends event-free survival and overall survival
      markedly in MM patients with low beta(2)-microglobulin levels. Long-term results
      of the total therapy trial indicate that patients who do not have chromosome 13
      deletions and present with low C-reactive protein and beta(2)-microglobulin
      levels have longer complete remissions than patients lacking these prognostic
      factors. Thalidomide shows clear evidence of antitumor activity possibly because
      of its antiangiogenic activity. Magnetic resonance imaging (MRI) indicates that
      bone marrow lesions become smaller or disappear while patients receive
      dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation
      chemotherapy and that patients who have a compete remission after diagnostic MRI
      have a superior event-free and overall survival than those who still have
      persistent MRI lesions. Prospective trials are underway to evaluate the
      effectiveness of consolidation therapy (total therapy II).

PMID- 11309706
TI  - Introduction: approaches to the therapeutic modulation of pulmonary host
      defenses.

PMID- 11309707
TI  - Antimicrobial proteins and peptides in host defense.
AB  - The antimicrobial properties of airways secretions and other mucosal secretions
      have been known for more than 70 years. Recent studies have identified a number
      of antimicrobial peptides and proteins that contribute to the antimicrobial
      activity of secretions, both under basal and inflamed conditions. Several
      peptides have properties that make them suitable for pharmaceutical development
      as topical or systemic antimicrobial agents.

PMID- 11309708
TI  - Immunomodulatory approaches to augment phagocyte-mediated host defense for
      treatment of infectious diseases.
AB  - Neutrophils, monocytes, and tissue-based macrophages are major cellular
      components of the innate immune system, which represents the initial line of host
      defense against invading pathogens. Four cytokines-granulocyte colony-stimulating
      factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF),
      macrophage colony-stimulating factor (M-CSF), and interferon-gamma (IFN-gamma)-
      have received increasing attention as potential adjunctive immunomodulatory
      agents for treatment of infectious diseases. Studies conducted in vitro and in
      vivo have shown that G-CSF, GM-CSF, and IFN-gamma can augment the functional
      antimicrobial activities of neutrophils. Similarly, GM-CSF, M-CSF, and IFN-gamma
      up-regulate multiple antimicrobial mechanisms in monocytes and macrophages.
      Studies conducted in animal models have shown the potential use of each of these
      cytokines for the treatment of infections caused by a variety of bacterial,
      fungal, and parasitic diseases. Because clinical experience with these
      immunomodulatory cytokines is relatively limited and currently investigational,
      controlled clinical trials will be necessary to define specific indications for
      the administration of these cytokines in therapeutic regimens.

PMID- 11309709
TI  - Gene therapy to modify pulmonary host defenses.
AB  - Respiratory infections remain a significant public health problem and are
      presently the 6th leading cause of death in the United States. Antibiotic
      resistant organisms are encountered increasingly in both community-acquired and
      nosocomial infections. Despite progress in antibiotic development, biological
      response modifiers may have increasing application to augment pulmonary host
      defenses against either drug-resistant infections or in high-risk hosts. Toward
      this end, gene therapy proposes to deliver biologicals as nucleic acids rather
      than protein. Gene therapy has the potential advantage of targeting the
      biological to specific cells or tissue compartments, and a more favorable
      pharmacokinetic profile. Data on gene delivery and efficacy in preclinical models
      of pulmonary infection are presented and discussed.

PMID- 11309710
TI  - Cytokine immunotherapy during bacterial pneumonia: from benchtop to bedside.
AB  - Bacterial pneumonia is a leading cause of morbidity and mortality within the
      United States and abroad. Although broad-spectrum antibiotic regiments have led
      to advances in the treatment of pneumonia, this approach has resulted in the
      recent emergence of multidrug-resistant bacteria. This adverse effect of
      aggressive antibiotic therapy underscores the importance for understanding the
      host inflammatory response to pulmonary bacterial infections. This knowledge can
      then lead to the development of therapeutic modalities aimed at augmenting host
      responses, resulting in enhanced resolution of bacterial pneumonia. Ideally,
      future treatment would combine immunoadjuvant and conventional antibiotic therapy
      for the treatment of life-threatening bacterial pneumonia. The detailed study of
      several distinct animal models of bacterial pneumonia has identified cytokines
      involved in eradication of bacteria deposited within the pulmonary airspace.
      Furthermore, these studies have led to promising preliminary findings in animal
      models using therapeutic cytokine immunotherapy.

PMID- 11309711
TI  - Cytokine treatment of bacterial pneumonia.
AB  - The lungs represent the largest epithelial surface area of the body and are
      repeatedly exposed to a variety of potential pathogens. The respiratory system
      has, therefore, developed an elaborate system of defense mechanisms to maintain
      the sterility of the lower airways. In the event of a defect, either
      developmental or acquired of any component of these defenses, the host is
      rendered susceptible to infection of the respiratory tract. Conventional therapy
      primarily focuses on the selection of appropriate antibiotic therapy and
      institution of supportive measures. In this article, we discuss emerging immune
      based strategies in the treatment of pneumonia that are primarily focused on
      amplification of the host defense system through the administration of cytokines.

PMID- 11309712
TI  - Immunotherapy of mycobacterial infections.
AB  - Mycobacterial infections cause enormous morbidity and mortality worldwide, but
      the critical aspects of the host response to them are still poorly understood.
      Over the past few years, cytokines have emerged as critical factors in
      mycobacterial control, with numerous mutations identified in the pathways
      controlling the production of, or response to, interferon gamma and its inducer,
      interleukin (IL)-12. These same cytokines may also have therapeutic activity
      against the nontuberculous mycobacteria and tuberculosis. In this article, the
      critical pathways and some of the relevant cytokines and studies are reviewed.
      This is a US government work. There are no restrictions on its use.

PMID- 11309713
TI  - Overview of host defense mechanisms in systemic mycoses and the basis for
      immunotherapy.
AB  - Host defense against systemic mycoses is multifactoral, depending on innate, as
      well as acquired, mechanisms. Innate resistance mechanisms include intact
      physical barriers, host proteins, nonspecific inflammatory responses, hormonal
      status, sex, and genetic make-up. However, the importance of any 1 factor in
      resistance to systemic fungal infections can vary depending on the causative
      agent. Macrophages and neutrophils play a critical role in the stasis or killing
      of these organisms by using the production of oxygen radicals, cationic proteins,
      nitric oxide (NO), and peroxides or iron deprivation. Although these cells are
      often ineffective in killing the organisms innately, activation of macrophages
      and neutrophils during an acquired immune response by the proinflammatory
      cytokine interferon-gamma as well as colony-stimulating factors increases the
      capacity of these cells for killing. A strong Th1 response can provide protective
      immunity, whereas a Th2 response can result in increased disease severity. The
      importance of native antibodies in resistance to mycoses remains in question.

PMID- 11309714
TI  - Antibody treatment of lower respiratory tract infections.
AB  - Antibody treatment of lower respiratory infection has a long history of success
      and is receiving renewed interest. A variety of polyclonal and monoclonal
      preparations are clinically available. Although used primarily for infection
      prophylaxis, these agents have limited applications in the treatment of
      established infections. Immune serum was the first effective treatment for
      pneumococcal pneumonia. Although long-supplanted by the advent of antibiotics,
      passive immunotherapy for pneumococcal and other infections is being revisited in
      an era of increasing antibiotic resistance and growing numbers of
      immunocompromised individuals. Limited clinical evidence supports the use of
      immune globulins in the treatment of pertussis and severe streptococcal
      infection. Bone marrow transplant recipients with lower respiratory infections
      caused by cytomegalovirus or respiratory syncytial virus also may benefit by
      adjunctive treatment with immune globulins. Additional indications for antibody
      treatment of respiratory infection may develop with further investigation.

PMID- 11309715
TI  - Anti-inflammatory treatment of acute and chronic pneumonia.
AB  - The inflammatory response to infection is necessary for host defense but can
      contribute to the systemic toxicity and lung injury that may result from
      pneumonia. In some settings, adjunctive treatment of lower respiratory infections
      with anti-inflammatory agents can reduce morbidity. Corticosteroids have a well
      documented role in the management of Pneumocystis carinii pneumonia complicating
      human immunodeficiency virus (HIV) infection. Corticosteroids also were found to
      reduce systemic symptoms of tuberculosis in a number of older studies, but their
      role as adjuncts to contemporary antimicrobial therapy are less clear.
      Corticosteroids also may be effective under some circumstances in the treatment
      of inflammatory sequelae of respiratory tract infection, such as tuberculous
      pleurisy, bronchiolitis obliterans organizing pneumonia, or prolonged acute
      respiratory distress syndrome. Nonsteroidal anti-inflammatory drugs may have
      limited applications in the modulation of chronic airway inflammation. Strategies
      targeting specific cytokines have not been effective to date, but remain active
      areas of investigation.

PMID- 11309716
TI  - Mycobacterium avium intracellulare complex as a cause of bronchiectasis.

PMID- 11309718
TI  - The incidence, etiology, and prevention of postresectional bronchopleural
      fistula.
AB  - Bronchopleural fistula (BPF) is a life-threatening complication after pulmonary
      resection. The incidence varies from 4.5% to 20% after pneumonectomy and is only
      0.5% after lobectomy. Certain patient characteristics increase this incidence.
      These include preoperative radiation to the chest, destroyed or infected lung
      from inflammatory disease, immunocompromised host, and insulin-dependent
      diabetes. Certain surgical techniques also increase the incidence. These include
      pneumonectomy, right-sided pneumonectomy, a long bronchial stump, residual cancer
      at the bronchial margin, devascularization of the bronchial stump, prolonged
      ventilation, or reintubation after resection and surgical inexperience. The best
      treatment of a BPF is prevention. Prevention centers around meticulous surgical
      technique and the liberal use of prophylactic, pedicled muscle flaps for the
      patient at increased risk. Survival of BPF depends on a high index of suspicion,
      early diagnosis, and aggressive surgical intervention.

PMID- 11309719
TI  - Management of bronchopleural fistula after lobectomy.
AB  - Bronchopleural fistula after lobectomy is fortunately a rare complication. In
      years past, this complication was encountered far more frequently. However, the
      morbidity associated with this complication is still significant. Bronchopleural
      fistulas develop in patients who are at increased risk of surgical morbidity
      because of their concomitant medical problems or as a result of chemotherapy for
      lung cancer or immunosuppression in transplant patients. These patients often
      present in a moribund, septic state, making their treatment even more difficult.
      Nevertheless, evaluation and management of these patients should proceed in a
      logical stepwise fashion. Evaluation of the patient with a bronchopleural fistula
      should proceed in a logical, stepwise manner form diagnosis to pulmonary
      rehabilitation.

PMID- 11309720
TI  - Management of postpneumonectomy empyema and bronchopleural fistula.
AB  - Empyema after pneumonectomy is often associated with a bronchopleural fistula
      (BDF) and has a significant mortality. Management options include systemic
      antibiotics and observation, adequate pleural drainage, appropriate parenteral
      antibiotics, removal of necrotic tissue, and obliteration of residual pleural
      space. We prefer to treat the empyema with the procedure originally described by
      Clagett and Geraci in 1963. They demonstrated that postpneumonectomy empyema
      could be successfully treated by open pleural drainage, frequent wet-to-dry
      dressing changes, and when the thorax was clean, secondary chest wall closure
      with obliteration of the pleural cavity with an antibiotic solution. Failure was
      most often caused by a persistent or recurrent fistula. Because of this, when a
      BPF is present, the original Clagett technique was modified to include
      transposition of a well-vascularized muscle to cover the stump at the time of
      open drainage to prevent further ischemia and necrosis. Our preference is
      intrathoracic transposition of extrathoracic skeletal muscle. The goals of
      therapy for postpneumonectomy empyema remain a healthy patient with a a healed
      chest wall and no evidence of drainage or infection. Excellent results can be
      obtained in more than 80% of patients by using the Clagett procedure and
      intrathoracic muscle transposition when a BPF is present.

PMID- 11309721
TI  - Management of the recalcitrant postpneumonectomy bronchopleural fistula: the
      transsternal transpericardial approach.
AB  - The authors review the management of postpneumonectomy bronchopleural fistulae
      and describe the place of the transsternal transpericardial approach, especially
      in the management of recalcitrant postpneumonectomy bronchopleural fistulae. The
      technique is described in detail, and the results of the published series are
      analyzed. The authors do recommend the use of this approach in the recalcitrant
      fistula that has failed standard approaches.

PMID- 11309722
TI  - Overview: postresectional bronchopleural fistula.

PMID- 11309723
TI  - Overview: procedure versus protection: an impossible separation.
AB  - This overview focuses upon the fundamental cohesion between myocardial protection
      and mechanical repair for surgical success. Currently, our attention is directed
      toward the natural evolution of more complex surgical methods, while there is
      slower rise in interest in advanced methods of protection. The absence of
      manuscripts on myocardial protection in major meetings suggests that the concept
      of protection has been solved, even though there remain reports of use of
      intraaortic balloon and mechanical devices that appear when protection is
      inadequate. This Seminar volume will introduce a series of articles about risk
      patients for whom evolving methods of protection are used. We will point out
      frontiers of protection that should develop together with advances in technical
      surgical approaches so that these two essential components that insure the safe
      conduct of cardiac operations can grow together.

PMID- 11309724
TI  - The role of integrated myocardial management in reoperative coronary surgery.
AB  - This article identifies the effect of integrated myocardial protection on
      outcomes after first-time repeat coronary artery bypass grafting (CABG). A
      consecutive series of 124 repeat CABG procedures were performed between January
      1996 and December 1999 with single aortic cross-clamping for all anastomoses and
      integrated myocardial protection. This included ischemia for heart dissection and
      distal grafting, and perfusion throughout the remainder of aortic clamping
      (including warm/cold, substrate/nonsubstrate-enhanced blood cardioplegia,
      delivered antegrade/retrograde, continuously/intermittently). Mean patient age
      was 67 +/ - 10 years (median 68) with 61% in New York Heart Association class IV
      and 23% in class III. Mean ejection fraction (EF) was 45 +/- 10.6% with EF 40% or
      less in 33% of patients and 30% or less in 20%. An average of 2.5 +/- 0.9 grafts
      were constructed. Cross-clamp times averaged 72 +/- 22 min and cardiopulmonary
      bypass time averaged 91 +/- 27 min. The average time from release of cross-clamp
      it disconnection from cardiopulmonary bypass (CPB) was 10 min. Median
      postoperative hospital stay was 6 days. hospital mortality was 2.4%, intra-aortic
      balloon pump (IABP) use 3.2%, stroke 0.8%, atrial fibrillation 11%, and
      reexploration for bleeding 2.4%. Integrated myocardial protection with blood
      cardioplegia is safe during reoperative coronary surgery. It allows rapid
      separation from CPB, limited IABP use, and low morbidity and mortality.

PMID- 11309725
TI  - Complex valvular procedures: ross, mitral, redos--time enough?
AB  - The possibility of a lengthy ischemic time is considered when evaluating complex
      valvular procedures. This consideration or even worry may influence the choice of
      valve replacement, repair offered, or actual acceptance of the case because of
      expected outcomes. With the use of an integrated, streamlined blood cardioplegic
      delivery, we believe these complex valvular procedures, even combined with
      revascularization, can be managed with good results. Additionally, this technique
      allows for sufficient protection to teach these same complex valvular repairs. A
      summary of a 10-year personal experience with the Ross procedure in 120 patients
      is covered. Aortic stenosis, insufficiency, and, particularly, infective
      endocarditis, have been managed with an overall surgical mortality rate of 2.5%.
      The endocarditis subset has a mortality of 0% with 100% cure of the infection.
      Data regarding complex mitral repairs and replacement are likewise included.

PMID- 11309726
TI  - The beating open heart for rebuilding ventricular geometry during surgical
      anterior restoration.
AB  - Heart failure is an increasing problem because of successful therapies in younger
      age groups and an overall increase in age in the general population. Ischemic
      cardiomyopathy secondary to myocardial infarction is the most prevalent entity
      among the several causes for cardiac failure. Among the surgical options for
      these patients, neither transplantation nor current ventricular assist devices
      are able to treat a sufficient number of patients. Ventricular restoration,
      however, may evolve as a surgical option to treat myocardial failure secondary to
      postinfarction ventricular dilatation. This procedure must be undertaken in high
      risk coronary artery bypass graft (CABG) patients in heart failure. We describe
      the techniques for both the conventional procedure (CABG +/- mitral valve [MV]
      repair) using cardioplegic methods, and the beating open heart for surgical
      anterior ventricular restoration (SAVR) for dyskinetic and akinetic areas in
      ischemic cardiomyopathies. This combined approach allows safe restoration of the
      ventricular geometry with minimal use of mechanical support (ie, intra-aortic
      balloon pump [IABP]) in 195 consecutive patients undergoing this procedure by
      members of an international team called the RESTORE group.

PMID- 11309727
TI  - Cardioplegia solutions--unproven herbal approach versus tested scientific study.
AB  - Cardioplegic solutions are used throughout the world, but must undergo careful
      testing before their clinical application. This study points out the importance
      of recognizing the hemodynamic changes produced by tested solutions so that
      appropriate decisions can be made in selecting crystalloid or blood solutions.
      Examples are provided, in which arbitrary changes made by the well-intentioned
      surgeon can produce damage through unanticipated alterations that are introduced
      without prior testing, and then used clinically. Recognition of the advantages
      and disadvantages of each solution is the underpinning of selection for clinical
      use so that unanticipated misadventures do not occur. Furthermore, the importance
      of making solutions in pharmacies with good manufacturing practices can avoid
      causing problems that would otherwise be prevented. Fundamentally, cardioplegic
      solutions are direct cardiac medications that must be tested as other drugs are
      so that unforeseen problems are avoided.

PMID- 11309728
TI  - Pediatric myocardial protection: an overview.
AB  - This article describes the experimental infrastructure and subsequent successful
      clinical application of a comprehensive bypass and cardioplegic strategy that
      limits intraoperative injury and improves postoperative outcomes in pediatric
      patients. The infant heart is at high risk of damage from poor protection because
      of preoperative hypertrophy, cyanosis, and ischemia. The background factors of
      vulnerability to damage caused by cyanosis and ischemia are discussed, together
      with studies of the infrastructure of strategies to use normoxia versus hyperoxia
      as bypass starts, white blood cell filtration, warm induction and reperfusion
      with substrate enhancements, multidose blood cardioplegia, and an integrated
      approach to allow ischemia only when vision is needed in pediatric surgeries.
      Data on cardioplegic management, including reducing calcium, increasing
      magnesium, and reducing perfusion pressure are shown, as used during this
      technique. These principles were applied to a consecutive series of 567 patients
      at the Heart Institute for Children and University of Illinois hospital over a 2
      year period. Included also were 72 patients with hypoplastic left heart over a 4
      year period with this myocardial management strategy. Application of these
      concepts may improve the safety of protection in infant hearts.

PMID- 11309729
TI  - Myocardial protection with leukocyte depletion in cardiac surgery.
AB  - A role of neutrophils in ischemia-reperfusion injury has been focused on as one
      of the mediating factors of inflammatory reactions. Current studies have reported
      the efficacy of leukocyte-depletion in reperfusion by using leukocyte removal
      filter to attenuate reperfusion injury during open heart surgeries. For clinical
      application, we have introduced leukocyte-depleted terminal blood cardioplegia
      (LDTC) in adult patients and leukocyte-depleted blood cardioplegia in pediatric
      patients. The results of elective surgery in noncompromised LDTC did not
      significantly alter the results in terms of leakage of creatine kinase (CK)-MB,
      production of malondialdehyde from myocardium, and dopamine dose required at the
      weaning from cardiopulmonary bypass compared with the whole-blood reperfusion or
      with terminal cardioplegia alone. In contrast, the results in emergency coronary
      artery bypass graft (CABG) patients differed significantly between the LDTC group
      and the other two groups. Leukocyte-depleted reperfusion was also effective in a
      similar fashion for patients with severe left ventricular hypertrophy caused by
      chronic aortic valve disease. Leukocyte-depleted blood cardioplegia was useful in
      pediatric patients. Thus, leukocyte depletion may be beneficial as an adjunct to
      terminal blood cardioplegia or blood cardioplegia during cardiac surgery to
      attenuate leukocyte-mediated ischemia-reperfusion injury in patients with
      compromised hearts, such as those with preoperative ischemic insults, severe left
      ventricular hypertrophy, and in pediatric patients.

PMID- 11309730
TI  - Myocardial protection for off-pump coronary artery bypass surgery.
AB  - Myocardial protection during off-pump coronary artery bypass surgery (OPCAB) is a
      multifactorial problem. Careful, individualized choice of graft sequence and
      maintenance of stable systemic hemodynamics are of central importance. Recently
      refined techniques for atraumatic rotation of the heart and visualization of
      coronary anastomoses allow precise and controlled grafting of all coronary
      territories without cardiopulmonary bypass in the large majority of cases.
      Perfusion-assisted direct coronary artery bypass (PADCAB) techniques, in which
      coronary perfusion pressure is independent of systemic arterial pressure, can
      avoid or abort a downward hemodynamic spiral, which may occasionally occur during
      complex, multivessel OPCAB. PADCAB promotes collateral myocardial perfusion and
      avoids the cumulative global effect of sequential episodes of regional ischemia,
      improving myocardial protection during OPCAB.

PMID- 11309731
TI  - The clinical consequences of the red cell storage lesion.

PMID- 11309732
TI  - Clinical and molecular basis of transfusion-induced immunomodulation: summary of
      the proceedings of a state-of-the-art conference.

PMID- 11309733
TI  - Phlebotomy, blood donation, and hereditary hemochromatosis.

PMID- 11309734
TI  - Measurement of platelet interactions with subendothelial substrata: relevance to
      transfusion medicine.

PMID- 11309735
TI  - Is there a place for hyperimmune globulins in the treatment of refractory
      infections?

PMID- 11309736
TI  - Enzymatic vitreous surgery.
AB  - Enzymatic manipulation of the vitreous and vitreoretinal juncture is currently in
      the process of being evaluated in many centers around the world. The goals of
      such manipulation are either to disinsert the posterior hyaloid from the retina
      surface in an atraumatic, very clean, cleavage plane or, at this point, to try to
      disinsert the peripheral vitreous from the neurosensory retina. In addition,
      enzymatic manipulation of the central vitreous in terms of liquefaction has also
      been evaluated. Although this is certainly the beginning of this type of vitreal
      surgery, adjuvant or alternative, it does appear to be a new and exciting area of
      vitreoretinal surgery.

PMID- 11309737
TI  - Macular epiretinal membranes.
AB  - Epiretinal membranes (ERM) are a common finding in older patients. Although they
      may be associated with numerous clinical conditions, most epiretinal membranes
      occur in the absence of ocular pathology. Patients symptoms range from asymptotic
      to complaints of severe vision loss and metamorphopsia. Epiretinal membranes are
      commonly classified according to their density, to the severity of retinal
      distortion and to associated biomicroscopic changes. Pars plana vitrectomy has
      been found to be effective in removing ERM from the macula, improving the visual
      acuity and decreasing metamorphopsia. Both idiopathic and secondary ERMs do well
      after surgery, although secondary ERMs showed a greater amount of improvement
      than idiopathic ones. Complications are frequent including accelerated
      postoperative nuclear sclerosis, retinal breaks and RD, macular edema, RPE and,
      occasionally, macular hole and hypotony. However only RD involving the macula
      have a worsening prognosis on final outcome.

PMID- 11309738
TI  - The expanding role of primary pars plana vitrectomy in the treatment of
      rhegmatogenous noncomplicated retinal detachment.
AB  - The surgical management of rhegmatogenous retinal detachment has evolved
      dramatically during the past 2 decades. Investigators have introduced and refined
      alternative techniques to scleral buckling surgery including pneumatic retinopexy
      and primary pars plana vitrectomy (PPV). Rapid parallel developments in
      instrumentation, including wide-angle viewing systems, perfluorocarbon liquids,
      novel vitrectomy machines, intraocular tamponades, and endolaser photocoagulators
      have led to increasing sophistication in primary PPV surgical techniques for the
      treatment of rhegmatogenous uncomplicated retinal detachment. However, the
      precise role of primary PPV in new uncomplicated retinal detachment remains
      debatable owing to the lack of controlled randomized trials. This article
      examines primary vitrectomy treatment for rhegmatogenous uncomplicated retinal
      detachment and presents the specific types of retinal detachments for which
      primary PPV may be optimal, according to personal and reported results, the
      surgical instrumentation and technique, as well as the complications and
      limitations of this surgical method.

PMID- 11309739
TI  - Vitrectomy for refractory diabetic macular edema.
AB  - Diabetic macular edema may occur or worsen as a consequence of vitreomacular
      traction in some eyes. The precise role of the posterior hyaloid in the
      pathogenesis of diabetic maculopathy remains unclear. The determination of which
      eyes might benefit from vitrectomy is the most challenging aspect in the
      treatment of this condition. Fluorescein angiography, B-scan untrasonography, and
      optical coherence tomography may be helpful in this regard. Most often, vitreous
      surgery is performed when diabetic macular edema persists despite multiple laser
      treatments. All reports published to date regarding vitrectomy for diabetic
      macular edema are uncontrolled and nonrandomized patient series. Visual
      improvement after vitrectomy is related to the duration of edema, as well as the
      extent of intraretinal lipid and vascular nonperfusion.

PMID- 11309740
TI  - Limited macular translocation for neovascular maculopathy.
AB  - Subfoveal choroidal neovascularization presents one of the most difficult
      challenges to vision. No treatment option has yet solved the problem of
      subretinal hemorrhage and fibrovascular scarring causing permanent photoreceptor
      degeneration and loss. Limited macular translocation provides a surgical approach
      to this challenge by moving the fovea onto an adjacent area of relatively normal
      subretinal space and pigment epithelium in a selected group of patients. The
      choroidal neovascularization, thus, becomes extrafoveal or juxtafoveal and can be
      treated with focal laser photocoagulation. This article describes the current
      technique of limited macular translocation and reviews early results. The
      procedure offers selected patients a chance to retain useful central vision.
      About 40% of patients at 6 months are able to read and drive (visual acuity
      >20/100). Complications including retinal detachment, hemorrhage, and macular
      folds have decreased with experience. Limited macular translocation is a
      promising approach to neovascular maculopathy, but needs ongoing careful
      evaluation.

PMID- 11309741
TI  - Silicone oil removal strategies.
AB  - Although it is widely accepted to use silicone oil in the treatment of very
      complex retinal detachments, there is no definite agreement on when and why
      silicone oil should be removed. Frequently found is a statement on the necessity
      of silicone oil removal after a certain period of time. However, the rate of
      retinal redetachment after silicone oil removal varies widely and appears to
      correlate with the underlying disease process and its severity. The literature on
      strategies of silicone oil removal, the rate of complications, and, thus, the
      risk-benefit ratio is scant. Therefore, for the discussion of silicone oil
      removal we rely on personal experience and the rather rare studies on silicone
      oil removal. Regarding the data given in the literature, the rate of
      vitreoretinal complications after silicone oil removal, even in cases with a
      clinically stable-appearing retinal situation, is rather high in severe
      proliferative vitreoretinopathy (PVR) and lower in most advanced cases of severe
      proliferative diabetic retinopathy (PDR) requiring silicone oil tamponade. The
      benefits of silicone oil removal are better in cases of cytomegalovirus retinitis
      or other situations without a PVR component. Silicone oil removal has to be
      considered a procedure of ill-defined risks, especially if silicone oil is really
      used as a last therapeutic resort in most severe cases of complicated retinal
      detachment. Further, exact criteria for the timing and safe removal of silicone
      oil in these complex vitreoretinal disorders still needs to be defined. A
      strategy for the removal of silicone oil is discussed.

PMID- 11309742
TI  - The management of subfoveal choroidal neovascular membranes and hemorrhage.
AB  - At the beginning of the past decade (1990), the Macular Photocoagulation Studies
      (MPS) were underway evaluating the efficacy of the treatment of subfoveal
      choroidal neovascularization (CNV) with conventional lasers. When this proved to
      limit the loss of vision and give little chance for improving vision,
      vitreoretinal surgeons turned to surgical approaches to treating these lesions.
      The surgical excision of subfoveal CNV has been under study for the remainder of
      the decade with the recent addition of macular/retinal translocation to attempt
      vision improvement for these patients. Other modalities including interferon
      therapy and external beam irradiation have proven ineffective, but new laser
      studies may offer promise with photosensitizing chemicals. Despite much study a
      single therapy that can reliably return sight to the majority of patients has not
      been developed. This article reviews the various therapies of the 1990s and
      renders some thoughts for the future.

PMID- 11309743
TI  - The macular buckling technique in the treatment of optic disk pit maculopathy.
AB  - In 1988 we introduced the macular buckling procedure for the treatment of optic
      disk pit maculopathy and we have been applying it since then. The surgery
      consists of a scleral sponge fixation of 7.5 x 5.5 mm at the posterior pole of
      the globe corresponding to the macula along the vertical axis of the 12 to 6
      o'clock meridian. No additional treatment of any kind (laser, diathermy, or
      cryotherapy) is used. The correct positioning of the sponge during the surgery is
      monitored by B-scan ultrasonography. Within the first week after surgery,
      indocyanine green angiography (ICG) is used to evaluate the choroidal
      circulation. During the same period, magnetic resonance imaging (MRI) of the
      orbit is performed to determine the sponge position in relation to the optic
      nerve. We analyze the results of 23 eyes with optic disk pit maculopathy that
      underwent surgery with the macular buckling technique between November 1988 and
      December 1998. In 20 of them the macula and the surrounding area of the retina
      became completely flat. No recurrence was noted in the successfully treated
      patients in the follow-up period, which ranged from 9 months to 10 years. Visual
      acuity was improved by 1 to 7 Snellen lines in 18 of the 23 patients. An
      improvement in visual field indices was also recorded. The sponge positioning
      between the temporal part of the optic disk and the macula acts mechanically and
      seems to provide a barrier that prevents the flow of the fluid from the pit
      toward the macula.

PMID- 11309744
TI  - Surgical treatment of retinal detachment owing to macular hole.
AB  - Retinal detachments owing to macular hole have a low prevalence and occur
      predominantly in myopic eyes. The choice of surgical technique is primarily based
      on the axial length of the globe and on the presence or absence of a posterior
      staphyloma and/or chorioretinal degenerations. Whereas patients with low myopia
      and no posterior staphyloma are best treated with primary pars plana vitrectomy
      and air tamponade, patients with marked myopia and large posterior staphylomas
      should be managed by combining a pars plana vitrectomy with laser
      photocoagulation of the macular hole rim under perfluorocarbon liquids and a
      temporary silicone oil tamponade. For the intermediate myopias the surgical
      technique has to be decided from patient to patient.

PMID- 11309745
TI  - Ancient mitochondrial DNA evidence for prehistoric population movement: the Numic
      expansion.
AB  - The mitochondrial DNA of modern Native Americans has been shown to fall into one
      of at least five haplogroups (A, B, C, D, or X) whose frequencies differ among
      tribal groups. The frequencies of these five haplogroups in a collection of
      ancient individuals from Western Nevada dating to between approximately 350-9,200
      years BP were determined. These data were used to test the hypothesis, supported
      by archaeological and linguistic data, that the current inhabitants of the Great
      Basin, the Numic speakers, are recent immigrants into the area who replaced the
      previous non-Numic inhabitants. The frequency distributions of haplogroups in the
      ancient and modern Native Americans differed significantly, suggesting that there
      is a genetic discontinuity between the ancient inhabitants and the modern Numic
      speakers, providing further support for the Recent Numic Expansion hypothesis.
      The distribution of mitochondrial haplogroups of the ancient inhabitants of the
      Great Basin is most similar to those of some of the modern Native American
      inhabitants of California.

PMID- 11309746
TI  - Paleoepidemiolgical patterns of trauma in a prehistoric population from central
      California.
AB  - Skeletal trauma was investigated in a large collection of human remains from
      central California (N = 162 aged and sexed adults). Lesions investigated included
      cranial and long bone fractures, projectile wounds, and dislocation. Long bone
      fractures were found in 10.5% of individuals; overall, incidence by element was
      2.3%. In addition, cranial injuries were found in 4.4% of complete adult crania.
      Projectile wounds were seen unambiguously in four individuals (with embedded
      obsidian fragments) and strongly suggested in two other individuals with
      partially healed lesions. Finally, one case of traumatic hip dislocation was also
      observed. In both incidence and patterning of injuries, this population is
      similar to other archeological groups from California. This evidence further
      supports earlier reports indicating that interpersonal aggression was quite
      common in prehistoric California.

PMID- 11309747
TI  - Eight hundred-year-old human remains from the Ituri tropical forest, Democratic
      Republic of Congo: the rock shelter site of Matangai Turu Northwest.
AB  - Little is known about human prehistory in the central African lowland tropical
      forest due to a paucity of archaeological evidence. Here we report results from
      our archaeological investigations of a late Holocene site in the northeast Congo
      Basin, with emphasis on a single skeleton from the rock shelter site of Matangai
      Turu Northwest, in the Ituri Forest, Democratic Republic of Congo. The skeleton
      dates from approximately 810 BP (1235 calibrated AD) and is associated with Later
      Stone Age lithics, animal bone and shell remains from wild taxa, fruit endocarps
      from forest trees, phytoliths from tropical forest plants, Late Iron Age
      ceramics, and a single iron artifact. Phytolith analysis indicates that the
      habitat was dense tropical forest, without evidence of domesticated food.

PMID- 11309748
TI  - A picture of tuberculosis in young Portuguese people in the early 20th century: a
      multidisciplinary study of the skeletal and historical evidence.
AB  - The aim of this study was to examine the evidence, and consider the differential
      diagnosis, for tuberculosis (TB) in juvenile individuals from early 20th century
      documented skeletons. There are 66 male and female juvenile individuals in the
      Coimbra Identified Skeletal Collection (CISC) with an age at death ranging from 7
      21 years. The individuals died between 1904-1936 in different areas of Coimbra,
      Portugal. Eighteen of these individuals died from TB affecting different parts of
      the body. Thirteen (72.2%) showed skeletal lesions that may be related to this
      infection. Of the 48 individuals with a non-tuberculous cause of death, only 2
      (4.2%) had skeletal changes that could be attributed to TB. The distribution of
      skeletal manifestations caused by the types of TB under study, based on
      macroscopic and radiological findings, is described and discussed. In addition,
      the medical records from 6 tuberculous individuals who died in Coimbra University
      Hospital (CUH) were analysed, and the information, including their diet and
      access to treatment, is presented. This work, based on data arising before
      antibiotics became available for treatment, can contribute to the future
      diagnosis of TB in non-documented skeletal material, and will facilitate a more
      reliable diagnosis of TB in juvenile individuals.

PMID- 11309749
TI  - Evolution of two human skeletal markers of the squatting position: a diachronic
      study from antiquity to the modern age.
AB  - Some human skeletal features that were produced through the actions of their
      bearers during life allow the reconstruction of postures. These can be typical of
      population groups. For example, tibial retroversion and lateral squatting facets
      are two skeletal markers closely related to the habit of squatting. The facets
      and the retroversion are induced by pressure and traction as a consequence of the
      hyperdorsiflexion of the knees and ankles. The examination of 543 tibiae and tali
      from French and American archaeological series, and dating between the 1st-20th
      century AD, reveals changes in squatting posture over time. This study shows that
      tibial retroversion tends to be a "precocity indicator" of the adoption of this
      posture, while the lateral squatting facet shows the intensity or regularity of
      the use of this posture. The results indicate that squatting was a regular
      behavior used until the end of the Middle Ages, and after this period a
      progressive decrease occurs. This tendency may be explained by different
      lifestyles in different time periods.

PMID- 11309750
TI  - Orthogonal factor coefficient development of subcutaneous adipose tissue
      topography (SAT-Top) in girls and boys.
AB  - The new optical device Lipometer allows noninvasive, quick, and safe
      determination of the thickness of subcutaneous adipose tissue (SAT) layers (in
      mm) at any site of the human body. The specification of 15 evenly distributed
      body sites enables the precise measurement of subcutaneous body fat distribution,
      so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Top was measured
      in 980 children aged 7-19 years. In this paper we describe the degree to which
      SAT-Top body sites are intercorrelated. We consider whether a meaningful
      reduction of data is possible using factor analysis, which factors can be
      extracted, and how SAT-Top data of children can be added to a factor value plot,
      depicting the essential results of age-dependent subcutaneous fat development.
      SAT layers situated on the same body area provide correlation coefficients up to
      +r = 0.91. Two factors are extracted: factor 1, containing all upper body sites
      (from neck to hip); and factor 2, consisting of all leg body sites. When all 980
      children are divided into three age groups in a factor value plot, the first age
      group (7-11 years) shows almost equal SAT-Top development in boys and girls.
      Afterwards, for the consecutive age groups 2 (11-15 years) and 3 (15-19 years),
      the age-dependent subcutaneous fat development of boys and girls progresses into
      nearly orthogonal directions.

PMID- 11309751
TI  - Growth of specific muscle strength between 6 and 18 years in contrasting
      socioeconomic conditions.
AB  - The influence of sex, age, and socioeconomic conditions on specific grip strength
      of 6-18-year-old individuals was studied among 1,704 males and 1,956 females
      belonging to the so-called "Cape Coloured" community in the western part of South
      Africa. Half of the participants of both sexes came from communities in the
      Greater Cape Town area where living conditions are comparable to those of middle
      class First World communities (high SES). The other half came from the poorest
      rural communities of Klein Karoo (low SES). Arm circumferences, triceps skinfold
      thickness, and grip strength of the right and of the left hand were greater in
      individuals from high SES at all ages. Females within each SES group had
      skinfolds thicker than males, especially at older ages, and were weaker. Specific
      grip strength (SS), estimated as grip strength per unit area of cross section of
      the fat-free arm, increased with age in each group, was greater in males, and was
      significantly lower in low SES groups, than in the high SES ones, especially
      during and after puberty. It seems that SES difference in SS will persist into
      adulthood. Sexual differences in SS can be attributed to hormonal differences;
      while the SS increase with age and the difference between SES groups find no
      clear explanation in current theories of muscle growth and development. Since the
      speed of neuromuscular reaction observed in our participants is slower among low
      SES individuals, it seems that the difference in neuromuscular control of
      strength may be responsible for our findings. Differences in muscle metabolism
      and hormonal regulation must also be considered.

PMID- 11309752
TI  - Waiting for Trivers and Willard: do the rich really favor sons?
AB  - Parental investment theory has been put forward as a major evolutionary argument
      explaining male or female biased birth sex ratio, the Trivers-Willard (T-W)
      hypothesis, predicting that parents living in good circumstances will bias their
      investment to sons, whereas parents in poor circumstances will bias their
      investment toward daughters. Tests of the T-W hypothesis on human beings have
      shown limited evidence for parents appearing to differentiate their investment to
      sons or daughters according to the reproductive potential of each sex. The
      present study tests the T-W hypothesis among a large contemporary Polish sample
      using first birth interval and extent of breastfeeding as measures of parental
      investment, and economic status and level of parental education as measures of
      parental condition. The extents to which parental investment and markers of
      parental condition vary by sex of the child were examined using log-linear
      analysis. Weak support for the T-W effect is found among families where fathers
      were best educated, where a greater proportion of first-born boys are breastfed
      longer than girls, while the opposite trend is observed among families with
      fathers with lowest levels of education. Although the present study does not
      fully support the T-W hypothesis, it gives evidence of greater investment in
      female offspring at the lower extremes of income, and greater investment in males
      at higher levels of income.

PMID- 11309753
TI  - Ontogeny of locomotion in rhesus macaques (Macaca mulatta): II. Postural and
      locomotor behavior and habitat use in a free-ranging colony.
AB  - This study quantifies changes in postural and locomotor behavior as well as
      habitat use across the life span of free-ranging rhesus macaques (Macaca mulatta)
      in the Cayo Santiago colony in Puerto Rico. It focuses on developmentally related
      changes from birth to adulthood, and complements an earlier study by Turnquist
      and Wells ([1994] J Hum Evol 26:487-499) on the early postnatal ontogeny of the
      musculoskeletal system of the same colony. A total of 6,551 locomotor and
      postural events was analyzed. Selection and use of substrate correlated well with
      age. The more sedentary adult and dependent infant select safe, wide, horizontal
      arboreal settings in contrast to the older Infant IIs and Juveniles, who are
      learning locomotor and postural skills through independent chase and play. Infant
      macaques, when independent, often employ a low center of gravity and widely
      abducted limbs in order to broaden their contact with the base of support. This
      study shows that the previously reported ontogenetic changes in morphology are
      closely paralleled by changes in postural and locomotor behavior, and these in
      turn are correlated to changes in habitat use, particularly during the formative
      years.

PMID- 11309754
TI  - Absence of regional affinities of Neandertal DNA with living humans does not
      reject multiregional evolution.
AB  - The recent extraction of mitochondrial DNA sequences from three European
      Neandertal fossils has led many to the conclusion that ancient DNA analysis
      supports the African replacement model of modern human origins and rejects models
      of multiregional evolution that propose some Neandertal ancestry in living
      humans. This conclusion is based, in part, on the lack of regional affinity of
      Neandertal DNA to that from living Europeans. Consideration of migration matrix
      models shows that this conclusion is premature, since under a model of
      interregional gene flow we expect to see similar levels of Neandertal ancestry in
      all contemporary regions, and living Europeans should not necessarily show closer
      affinity. The absence of regional affinity in Neandertal DNA does not distinguish
      between replacement and multiregional models.

PMID- 11309755
TI  - TNM: principles, history, and relation to other prognostic factors.
AB  - The TNM classification system describes the anatomic extent of cancer. The
      ability of TNM to separately classify the individual tumor (T), lymph node (N),
      and metastatic (M) elements and then group them into stages differs from other
      cancer staging classifications, which are concerned only with summarized groups.
      The objectives of TNM classification are to aid the clinician in the planning of
      treatment, to give some indication of prognosis, to assist in the evaluation of
      the results of treatment, and to facilitate the exchange of information. The most
      important challenge facing TNM is how to interface with the great numbers of
      nonanatomic prognostic factors that are currently in use or under study. As
      nonanatomic prognostic factors become widely used, TNM provides an inviting
      foundation upon which to build a prognostic classification; however, there is a
      risk that TNM will be overwhelmed by such a variety of prognostic data. An
      anatomic extent of disease classification is needed to select the initial
      therapeutic approach, stratify patients for therapeutic studies, evaluate
      nonanatomic prognostic factors at specific anatomic stages, compare the weight of
      nonanatomic factors with extent of disease, and communicate extent of disease
      data in a uniform manner. Methods are needed to express overall prognosis without
      losing the vital anatomic content of TNM. These methods should be able to
      integrate multiple prognostic factors, including TNM, yet permit TNM to remain
      intact and distinct.

PMID- 11309756
TI  - Introductory remarks to the Conference on Prognostic Factors and Staging in
      Cancer Management: Contributions of Artificial Neural Networks and Other
      Statistical Methods.

PMID- 11309757
TI  - Clinical problems, computational solutions: a vision for a collaborative future.

PMID- 11309758
TI  - Computerized medical records in the Department of Veterans Affairs.
AB  - The VA Medical Center in Washington, DC, was the nexus for a number of
      computerization projects that were initiated by the Department of Veterans
      Affairs. The culmination of these initiatives is a software package that presents
      the complete electronic patient record in an easy-to-use graphic user interface.
      This record combines text data from the legacy data base, diagnostic images from
      patient procedures, electrocardiograms from a commercial server, an Internet
      connection, and a hospital web site with pertinent reference information. The
      information is available in over 1000 places in the hospital and can be accessed
      remotely using a remote access server. The computerization of the medical record
      has improved hospital efficiency, has made physician access to patient
      information more reliable, has opened new opportunities for patient education,
      and has given healthcare providers more time to care for patients.

PMID- 11309759
TI  - Challenges in prognostic analysis.

PMID- 11309760
TI  - Artificial neural networks: opening the black box.
AB  - Artificial neural networks now are used in many fields. They have become well
      established as viable, multipurpose, robust computational methodologies with
      solid theoretic support and with strong potential to be effective in any
      discipline, especially medicine. For example, neural networks can extract new
      medical information from raw data, build computer models that are useful for
      medical decision-making, and aid in the distribution of medical expertise.
      Because many important neural network applications currently are emerging, the
      authors have prepared this article to bring a clearer understanding of these
      biologically inspired computing paradigms to anyone interested in exploring their
      use in medicine. They discuss the historical development of neural networks and
      provide the basic operational mathematics for the popular multilayered
      perceptron. The authors also describe good training, validation, and testing
      techniques, and discuss measurements of performance and reliability, including
      the use of bootstrap methods to obtain confidence intervals. Because it is
      possible to predict outcomes for individual patients with a neural network, the
      authors discuss the paradigm shift that is taking place from previous "bin-model"
      approaches, in which patient outcome and management is assumed from the
      statistical groups in which the patient fits. The authors explain that with
      neural networks it is possible to mediate predictions for individual patients
      with prevalence and misclassification cost considerations using receiver
      operating characteristic methodology. The authors illustrate their findings with
      examples that include prostate carcinoma detection, coronary heart disease risk
      prediction, and medication dosing. The authors identify and discuss obstacles to
      success, including the need for expanded databases and the need to establish
      multidisciplinary teams. The authors believe that these obstacles can be overcome
      and that neural networks have a very important role in future medical decision
      support and the patient management systems employed in routine medical practice.

PMID- 11309761
TI  - Comparison of artificial neural networks with other statistical approaches:
      results from medical data sets.
AB  - BACKGROUND: In recent years, considerable attention has been given to the
      development of sophisticated techniques for exploring data sets. One such class
      of techniques is artificial neural networks (ANNs). Artificial neural networks
      have many attractive theoretic properties, specifically, the ability to detect
      non predefined relations such as nonlinear effects and/or interactions. These
      theoretic advantages come at the cost of reduced interpretability of the model
      output. Many authors have analyzed the same data set, based on these factors,
      with both standard statistical methods (such as logistic or Cox regression) and
      ANN. METHODS: The goal of this work is to review the literature comparing the
      performance of ANN with standard statistical techniques when applied to medium to
      large data sets (sample size > 200 patients). A thorough literature search was
      performed, with specific criteria for a published comparison to be included in
      this review. RESULTS: In the 28 studies included in this review, ANN outperformed
      regression in 10 cases (36%), was outperformed by regression in 4 cases (14%),
      and the 2 methods had similar performance in the remaining 14 cases (50%).
      However, in the 8 largest studies (sample size > 5000), regression and ANN tied
      in 7 cases, with regression winning in the remaining case. In addition, there is
      some suggestion of publication bias. CONCLUSIONS: Neither method achieves the
      desired performance. Both methods should continue to be used and explored in a
      complementary manner. However, based on the available data, ANN should not
      replace standard statistical approaches as the method of choice for the
      classification of medical data.

PMID- 11309762
TI  - Prediction of individual patient outcome in cancer: comparison of artificial
      neural networks and Kaplan--Meier methods.
AB  - BACKGROUND: There is a great need for accurate treatment and outcome prediction
      in cancer. Two methods for prediction, artificial neural networks and Kaplan-
      Meier plots, have not, to the authors' knowledge, been compared previously.
      METHODS: This review compares the advantages and disadvantages of the use of
      artificial neural networks and Kaplan--Meier curves for treatment and outcome
      prediction in cancer. RESULTS: Artificial neural networks are useful for
      prediction of outcome for individual patients with cancer because they are as
      accurate as the best traditional statistical methods, are able to capture complex
      phenomena without a priori knowledge, and can be reduced to a simpler model if
      the phenomena are not complex. Kaplan--Meier plots are of limited accuracy for
      prediction because they require partitioning of variables, require cutting
      continuous variables into discrete pieces, and can only handle one or two
      variables effectively. CONCLUSIONS: Artificial neural networks are an efficient
      statistical method for outcome prediction in cancer that utilizes all available
      powerful prognostic factors and maximizes predictive accuracy. Use of Kaplan-
      Meier plots for predictions is discouraged because of serious technical
      limitations and low accuracy.

PMID- 11309763
TI  - Artificial neural networks for prostate carcinoma risk assessment. An overview.

PMID- 11309764
TI  - Impact of different variables on the outcome of patients with clinically confined
      prostate carcinoma: prediction of pathologic stage and biochemical failure using
      an artificial neural network.
AB  - BACKGROUND: The advent of advanced computing techniques has provided the
      opportunity to analyze clinical data using artificial intelligence techniques.
      This study was designed to determine whether a neural network could be developed
      using preoperative prognostic indicators to predict the pathologic stage and time
      of biochemical failure for patients who undergo radical prostatectomy. METHODS:
      The preoperative information included TNM stage, prostate size, prostate specific
      antigen (PSA) level, biopsy results (Gleason score and percentage of positive
      biopsy), as well as patient age. All 309 patients underwent radical prostatectomy
      at the University of Colorado Health Sciences Center. The data from all patients
      were used to train a multilayer perceptron artificial neural network. The failure
      rate was defined as a rise in the PSA level > 0.2 ng/mL. The biochemical failure
      rate in the data base used was 14.2%. Univariate and multivariate analyses were
      performed to validate the results. RESULTS: The neural network statistics for the
      validation set showed a sensitivity and specificity of 79% and 81%, respectively,
      for the prediction of pathologic stage with an overall accuracy of 80% compared
      with an overall accuracy of 67% using the multivariate regression analysis. The
      sensitivity and specificity for the prediction of failure were 67% and 85%,
      respectively, demonstrating a high confidence in predicting failure. The overall
      accuracy rates for the artificial neural network and the multivariate analysis
      were similar. CONCLUSIONS: Neural networks can offer a convenient vehicle for
      clinicians to assess the preoperative risk of disease progression for patients
      who are about to undergo radical prostatectomy. Continued investigation of this
      approach with larger data sets seems warranted.

PMID- 11309765
TI  - Evaluation of artificial neural networks for the prediction of pathologic stage
      in prostate carcinoma.
AB  - BACKGROUND: Currently, the standard for predicting pathologic stage from
      information available at the time of prostate biopsy is the "Partin nomograms"
      that were derived using logistic regression analysis. The authors retrospectively
      reviewed a large series of men with clinically localized prostate carcinoma who
      underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy.
      They then utilized pathologic and clinical data at the time of prostate biopsy to
      develop and test an artificial neural network (ANN) to predict the final
      pathologic stage for this group of men. They then compared the results of ANN
      with the previous nomograms. METHODS: Five thousand seven hundred forty-four men
      were treated at the authors' institution from 1985 to 1998. An ANN was developed
      using two randomly selected training and validation sets for predicting
      pathologic stage. Input variables included age, preoperative serum prostate
      specific antigen level, clinical TNM (tumor, lymph node, and metastasis)
      classification, and Gleason score from the biopsy specimen. Outcomes included
      organ confinement and lymph node involvement status. RESULTS: The ANN was
      slightly superior to the nomograms in predicting pathologic stage, such as organ
      confinement and lymph node involvement status. CONCLUSIONS: In predicting organ
      confinement and lymph node involvement status, ANN was more accurate and had a
      larger area under ROC than the nomograms based on the logistic regression method.
      Artificial neural network models can be developed and used to better predict
      final pathologic stage when preoperative pathologic and clinical features are
      known.

PMID- 11309766
TI  - The problem of cutoff levels in a screened population: appropriateness of
      informing screenees about their risk of having prostate carcinoma.
AB  - BACKGROUND: Transrectal prostate biopsy decisions often have been based on
      absolute cutoff values for total and free prostate-specific antigen (PSA). The
      authors decided that it would be more appropriate to develop risk profiles for
      the individual patient to allow him to decide whether to undergo a prostate
      biopsy. METHODS: To develop risk profiles, the authors first used multivariate
      logistic regression analysis to analyze 2054 males who were part of the Tyrol
      (Austria) PSA Screening Project. Second, artificial neural network (ANN) analyses
      were performed using data from 3474 males who also were part of the Tyrol PSA
      Screening Project and who had undergone prostate biopsy. These analyses were
      compared with standard cutoff levels of specificity for the detection of prostate
      carcinoma. RESULTS: To the authors' knowledge, this was the first time that
      multivariate logistic regression analysis was used to decide whether to perform
      prostate biopsies based on risk profiles rather than on single cutoff levels. For
      the detection of prostate carcinoma, at sensitivity levels of 90--95%, the ANN
      was 150--200% more specific than the standard cutoff points. For screened
      volunteers with total PSA levels below 4 ng/mL, ANN showed a lower cancer
      predictive ability in comparison with volunteers with total PSA levels above 4
      ng/mL. However, the ANN was approximately 150--200% more specific than the
      standard cutoff levels in both groups. CONCLUSIONS: At high sensitivity levels,
      ANN increased the specificity for prostate carcinoma detection in a PSA-based
      screened population. The improvement in specificity between standard cutoff
      levels and ANN ranged between 150--200% and was not affected by the presence of
      benign prostatic hyperplasia or prostatitis.

PMID- 11309767
TI  - Neural network and regression predictions of 5-year survival after colon
      carcinoma treatment.
AB  - BACKGROUND: The Commission on Cancer data from the National Cancer Data Base
      (NCDB) for patients with colon carcinoma was used to develop several artificial
      neural network and regression-based models. These models were designed to predict
      the likelihood of 5-year survival after primary treatment for colon carcinoma.
      METHODS: Two modeling methods were used in the study. Artificial neural networks
      were used to select the more important variables from the NCDB database and model
      5-year survival. A standard parametric logistic regression also was used to model
      survival and the two methods compared on a prospective set of patients not used
      in model development. RESULTS: The neural network yielded a receiver operating
      characteristic (ROC) area of 87.6%. At a sensitivity to mortality of 95% the
      specificity was 41%. The logistic regression yielded a ROC area of 82% and at a
      sensitivity to mortality of 95% gave a specificity of 27%. CONCLUSIONS: The
      neural network found a strong pattern in the database predictive of 5-year
      survival status. The logistic regression produced somewhat less accurate, but
      good, results.

PMID- 11309769
TI  - Prognostic factors in clinical decision making: the future.

PMID- 11309768
TI  - Fifteen-year prognostic discriminants for invasive breast carcinoma: National
      Surgical Adjuvant Breast and Bowel Project Protocol-06.
AB  - BACKGROUND: This report updated previous findings, at the 15-year mark, of the
      National Surgical Breast and Bowel Project (NSAPB) Protocol B-06 with respect to
      the treatment of invasive breast carcinoma and the effects of pathologic features
      and the effects of some clinical features on its natural history. METHODS: Thirty
      one pathologic and 6 clinical features that were observed in a pathologic subset
      of 1039 evaluable patients were assessed as to their value in predicting
      survival, in predicting ipsilateral breast tumor recurrence (IBTR), and in
      predicting the necessity for local breast irradiation after lumpectomy. The
      patients had been randomly assigned to treatment by lumpectomy without local
      irradiation or to treatment by lumpectomy with local irradiation of the breast. A
      traditional and another statistical method were used for this purpose. RESULTS:
      Multivariate analyses revealed that the presence of IBTR, race, histologic tumor
      type, nodal status, nuclear grade, and blood vessel invasion affected survival
      independently. Treatment, patient age, nuclear grade, presence of intraductal
      carcinoma, and a lymphocytic tumor infiltrate were features that predicted IBTR
      by multivariate analyses. Irradiation reduced IBTR from 36% to 12% in the
      analyzed cohort. A test of interaction failed to reveal any pathologic or
      clinical feature that might have allowed for the omission of local irradiation of
      the breast after lumpectomy. CONCLUSIONS: In addition to the influence of
      pathologic and clinical features on patient survival and IBTR, the site,
      histopathologic features, and time of occurrence of the latter allowed for
      insights into some important biologic considerations concerning invasive breast
      carcinoma.

PMID- 11309771
TI  - The annual Papanicolaou test. Women's safety and public policy.

PMID- 11309772
TI  - An accurate and precise methodology for routine determination of the false
      negative rate of Papanicolaou smear screening.
AB  - BACKGROUND: Although the false-negative rate (FNR) is the most important quality
      control measure for Papanicolaou smear screening, accurate, precise, and feasible
      methods for determining this value are lacking. METHODS: The author undertook an
      analysis and review of the literature. RESULTS: The best estimates of the FNR
      using atypical squamous cells of undetermined significance (ASCUS) as a threshold
      range from 17% to 61%. Sources of error in the accuracy of this measure that must
      be accounted for include the FNR of the review method, differences in diagnostic
      thresholds between the original diagnostic method and the review method, and
      differences in diagnostic accuracy between the original diagnostic method and the
      review method. Statistically precise (valid to within 10%) measurement of this
      value in laboratories with an ASCUS+ rate of 7% can be made from interlaboratory
      rescreening of approximately 1200-1500 randomly selected normal and abnormal
      slides along with both laboratories rediagnosing without rescreening 300-400
      benign cellular change and ASCUS slides to determine the difference in diagnostic
      threshold. Consensus for each slide is not required with this method. Changing
      the threshold to low grade squamous intraepithelial lesion (best estimate FNR, 14
      58%) requires review of significantly more slides to achieve the same statistical
      level of precision. CONCLUSIONS: Detailed analysis of the sources of error in
      determining the FNR allow creation of methods that are relatively unbiased,
      feasible, and testable and whose accuracy and precision can be determined.

PMID- 11309773
TI  - Should the cytologic diagnosis of "atypical squamous cells of undetermined
      significance" be qualified? An assessment including comparison between
      conventional and liquid-based technologies.
AB  - BACKGROUND: The diagnosis of atypical squamous cells of undetermined significance
      (ASCUS) remains an enigma for the treating physician, because it encompasses both
      benign, reactive, as well as preneoplastic and possibly neoplastic conditions. To
      address this problem, The Bethesda System recommends qualifying the ASCUS
      diagnosis. This study analyzes the difference in the follow-up results between
      the various groups of patients with an ASCUS diagnosis as outlined by the
      Criteria Committee: favor premalignant (ASCUS-P), favor reactive (ASCUS-R), and
      unqualified (ASCUS-C). The outcome, based on follow-up biopsies and/or
      cytologies, for both the conventional Papanicolaou smear (CS) and liquid-based
      (LB) methodologies is compared. METHODS: The CS and LB biopsies and/or cytologies
      included 590 patients and 137 patients, respectively, who had an initial
      diagnosis of ASCUS. The final outcome after subsequent biopsy and cytology within
      a 1-year period for each methodology was tabulated. Furthermore, the addition of
      qualifiers for each diagnosis was tabulated for both cytology and biopsy follow
      up and compared between CS and LB technologies. RESULTS: For CS, 29 patients
      (8.6%) were found to have squamous intraepithelial lesions (SIL) on subsequent
      cytologic smears, and 176 patients (63.7%) had SIL on biopsy follow-up. For LB,
      these numbers were 17 patients (19.1%) and 56 patients (65.1%), respectively.
      Regardless of the qualification used in the initial CS biopsy or cytology, over
      90% of the subsequent smears resulted in a benign diagnosis. Biopsy outcomes
      after CS diagnoses of ASCUS-P, ASCUS-R, and ASCUS-C showed SIL in 80%, 53%, and
      66% of patients, respectively. For LB diagnoses, subsequent smears detected SIL
      in 33% of patients with a diagnosis of ASCUS-P, 22% of patients with a diagnosis
      of ASCUS-R, and 12% of patients with a diagnosis of ASCUS-C. Biopsy outcomes
      after LB diagnoses of ASCUS-P, ASCUS-R, and ASCUS-C showed SIL in 68%, 64%, and
      66% of patients, respectively. CONCLUSIONS: There appears to be no statistically
      valid benefit from a clinical point of view in qualifying an ASCUS interpretation
      by either CS or LB, except for CS evaluation of patients with a diagnosis of
      ASCUS-P.

PMID- 11309774
TI  - Significance of a diagnosis of atypical squamous cells of undetermined
      significance for Papanicolaou smears in perimenopausal and postmenopausal women.
AB  - BACKGROUND: The current study was conducted to determine the significance of a
      diagnosis of atypical squamous cells of undetermined significance (ASCUS) in
      perimenopausal and postmenopausal women. METHODS: The reports for all
      Papanicolaou (Pap) smears viewed in the study institution's cytology laboratory
      over a 6-month period were reviewed. Women were divided into premenopausal (age <
      or = 45 years), perimenopausal (ages 46-54 years), and postmenopausal (age > or =
      55 years) categories. Slide review and 2-year follow-up were obtained for
      selected cases diagnosed as ASCUS. ASCUS cases among the perimenopausal women
      were compared with an age-matched control group. RESULTS: The total number of
      abnormal Pap smears in the premenopausal, perimenopausal, and postmenopausal
      categories were 770 (6.8%), 104 (4.3%), and 67 (2.9%), with 482, 83, and 41
      diagnoses of ASCUS, respectively. The ratio of ASCUS to squamous intraepithelial
      lesions (SIL) was 2.2 overall and 1.9, 7.5, and 4.1, respectively, for each group
      (P < 0.001). The positive predictive value for a diagnosis of SIL on subsequent
      Pap smears or biopsies was 22%, 12.2%, and 29.7%, respectively. Slide review
      showed that the premenopausal ASCUS cases appeared to have a higher percentage of
      nuclear-cytoplasmic ratio increase and nuclear membrane irregularities compared
      with the other categories (P = 0.03 and P = 0.02, respectively) and the
      perimenopausal group was found to have more ASCUS in metaplastic cells (P =
      0.03). In perimenopausal women, slides diagnosed as ASCUS demonstrated more air
      drying artifact than the control group (P = 0.004) but had less obvious atrophy
      (P = 0.01). CONCLUSIONS: Despite a decreased abnormality rate with increasing
      age, the results of the current study show that the perimenopausal and
      postmenopausal groups appear to have elevated ASCUS-to-SIL ratios. ASCUS appears
      to have a particularly low positive predictive value for SIL in perimenopausal
      women, and therefore most likely is overcalled in this age group. This may be
      attributable in part to air-drying artifact and subtle atrophic changes.

PMID- 11309775
TI  - The human false-negative rate of rescreening Pap tests. Measured in a two-arm
      prospective clinical trial.
AB  - BACKGROUND: Routine quality control rescreening often is used to calculate the
      false-negative rate (FNR) of gynecologic cytology. Theoretic analysis suggests
      that this is not appropriate, due to the high FNR of rescreening and the
      inability to actually measure it. The authors sought to determine the FNR of
      manual rescreening in a large, prospective, two-arm clinical trial using an
      analytic instrument in the evaluation. METHODS: The results of the Autopap System
      Clinical Trial, encompassing 25,124 analyzed slides, were reviewed. The false
      negative and false-positive rates at various thresholds were determined for
      routine primary screening, routine rescreening, Autopap primary screening, and
      Autopap rescreening by using a simple, standard methodology. RESULTS: The FNR of
      routine manual rescreening at the level of atypical squamous cells of
      undetermined significance (ASCUS) was 73%, more than 3 times the FNR of primary
      screening; 11 cases were detected. The FNR of Autopap rescreening was 34%; 80
      cases were detected. Routine manual rescreening decreased the laboratory FNR by
      less than 1%; Autopap rescreening reduced the overall laboratory FNR by 5.7%. At
      the same time, the false-positive rate for Autopap screening was significantly
      less than that of routine manual screening at the ASCUS level (4.7% vs. 5.6%; P <
      0.0001). Rescreening with the Autopap system remained more sensitive than manual
      rescreening at the low grade squamous intraepithelial lesions threshold (FNR of
      58.8% vs. 100%, respectively), although the number of cases rescreened was low.
      CONCLUSIONS: Routine manual rescreening cannot be used to calculate the FNR of
      primary screening. Routine rescreening is an extremely ineffective method to
      detect error and thereby decrease a laboratory's FNR. The Autopap system is a
      much more effective way of detecting errors within a laboratory and reduces the
      laboratory's FNR by greater than 25%.

PMID- 11309776
TI  - CD4 T-cell count, viral load, and squamous intraepithelial lesions in women
      infected with the human immunodeficiency virus.
AB  - BACKGROUND: Recent studies have reported an increased incidence of squamous
      intraepithelial lesions in women infected with the human immunodeficiency virus
      (HIV). However, to the authors' knowledge there are scarce data regarding the
      relation between the CD4 T-lymphocyte count (CD4+), HIV viral load, and the
      development of cervical dysplasia as evidenced by cervicovaginal cytology. The
      objective of the current study was to examine the association between
      cervicovaginal smears (with and without squamous lesions) from HIV-infected women
      and their CD4+ counts and HIV viral load. METHODS: Two hundred ninety-six
      cervicovaginal smears from 108 HIV-infected women were reviewed and classified
      according to the Bethesda system. Abnormal cytologies (n = 74) were followed by
      colposcopy and/or biopsy. CD4+ counts and HIV viral loads were available at the
      time of the cytologic evaluation. Statistical analysis was performed using the
      Student t test and the Mann-Whitney U test. RESULTS: The control group (n = 222)
      had significantly higher CD4+ counts (378 vs. 246 cells/microL; P < 0.001)
      compared with the group with cervical lesions. There was no apparent difference
      between the CD4+ counts from women with low grade lesions and those from women
      with high grade lesions. The HIV viral load was significantly higher in patients
      with cytologic abnormalities than in those with negative Papanicolaou smears (P =
      0.006). CONCLUSIONS: The degree of immunosuppression may contribute to the
      development of intraepithelial lesions in HIV-positive women, but once the lesion
      is established disease progression may not be affected by the CD4+ counts.

PMID- 11309777
TI  - Prognostic significance of combined conventional and immunocytochemical cytology
      for peritoneal washings in endometrial carcinoma.
AB  - BACKGROUND: Noncancerous cells simulating adenocarcinoma cells may interfere with
      the analysis of peritoneal cytology (PC) in patients with endometrial carcinoma.
      Immunocytochemistry (ICC) may improve the diagnosis of PC. METHODS: PC slides
      from 115 patients with endometrial carcinoma were reviewed. Suspicious or
      positive cell clusters were recovered with a cell transfer method and were
      subjected to ICC for MOC-31, cytokeratin 5/6, and p53. Conventional Papanicolaou
      staining and ICC results were compared directly on the same cells. RESULTS: By
      combined conventional and immunocytochemical PC (CONV-ICC-PC), cytodiagnosis was
      positive in 18 of 115 patients (15.7%) and suspicious in 3 of 115 patients
      (2.6%). According to a multivariate Cox regression analysis of patients with
      tumors confined to the uterus that included grade, myometrial invasion, cervical
      involvement, and CONV-ICC-PC, only CONV-ICC-PC was an independent prognostic
      factor (P < 0.05). A multivariate analysis for all of the patients studied that
      compared CONV-ICC-PC with staging variables revealed that only peritoneal
      metastasis (P < 0.0001) and lymph node metastasis (P < 0.01) were independent
      prognostic factors. When peritoneal metastases were excluded, CONV-ICC-PC (P <
      0.01) and lymph node metastasis (P < 0.0025) were the independent prognostic
      factors. By cell transfer and p53 immunostaining in samples from 14 patients with
      malignant cells in their peritoneal washings, no deaths occurred among 5 patients
      with negative p53, whereas 5 of 9 patients with positive p53 died of disease at
      the time of data analysis. CONCLUSIONS: MOC-31 immunostaining improves the
      diagnosis of PC in endometrial carcinoma. Positive PC is an important prognostic
      factor for patients with endometrial carcinoma confined to the uterus. The p53
      positive cells in PC have possible prognostic significance.

PMID- 11309778
TI  - Small-sized adenocarcinoma of the lung. Cytologic characteristics and clinical
      behavior.
AB  - BACKGROUND: Although the cytologic characteristics of advanced adenocarcinomas of
      the lung have been described, the unique cytologic features of early
      adenocarcinomas have not been established. METHODS: Cytologic specimens from 193
      patients with small-sized lung adenocarcinoma, up to 2 cm in dimension, were
      reviewed. Cytologic investigations were performed on sputum, bronchial brushings
      or washings, or fine-needle aspirates obtained from the patients preoperatively.
      The cytologic characteristics of early adenocarcinoma were confirmed with Image
      Processor for Analytical Pathology from Sumitomo Chemical Co., Ltd. RESULTS:
      Nuclear size, variations in nuclear size, appearance of nucleolus, and nuclear
      atypia of the adenocarcinoma cells were found to differ between the various
      histologic subtypes of adenocarcinoma. The nuclei in small but advanced
      adenocarcinoma were generally larger and showed more variation in size than those
      in early adenocarcinoma (localized bronchioloalveolar carcinoma). CONCLUSIONS:
      Surgically curable, early adenocarcinomas of the lung were found to have a unique
      cytologic appearance, including small nuclear size and slight variation in
      nuclear size. Using these unique characteristics, they can be distinguished
      easily from advanced adenocarcinomas.

PMID- 11309779
TI  - Critical clinicopathologic analysis of 23 cases of fine-needle breast sampling
      initially recorded as false-positive. The 44-year experience of the Institut
      Curie.
AB  - BACKGROUND: Because false-positive cytologic diagnoses in breast tumors are rare,
      few cases have been reported, although their consequences may be highly
      detrimental to the patient. The authors report the Institut Curie's experience,
      by using a multidisciplinary approach. METHODS: Of 9334 benign breast tumors
      examined preoperatively for cytologic diagnosis by fine-needle sampling (FNS),
      the 23 (0.25%) FNS cases considered to be false-positive were retrospectively
      reviewed and analyzed. RESULTS: Tumors were situated close to the nipple in 7
      cases and away from the nipple in 16 cases. Tumor stage was T0 for 1 case, T1 for
      18 cases, and T2 for 4 cases. Radiologically, six tumors were classified as
      malignant, seven as indeterminate or suspicious, and nine as benign. Three of six
      tumors studied by flow cytometry were DNA aneuploid. Based on a multidisciplinary
      clinicopathologic review, 20 FNS cases were finally classified as false-positive,
      and the remaining 3 tumors with malignant FNS and subsequent benign histology
      were classified as true-positive, because local and/or metastatic progression was
      observed in the short term. CONCLUSIONS: The authors' review suggests two
      categories of false-positive cases: the first in which cytologic benign patterns
      are overdiagnosed, and the second in which atypical morphologic criteria were
      present. Nevertheless, as shown by the malignant course in three cases, patients
      with malignant preoperative FNS and corresponding benign histology always require
      close clinical follow-up. Finally, surgical overtreatment rate could be decreased
      if all radiologically benign tumors with positive/suspicious FNS were subject to
      intraoperative frozen section examination.

PMID- 11309780
TI  - The spectrum of cytologic features in nonproliferative breast lesions.
AB  - BACKGROUND: The reliability of cytologic criteria to classify nonproliferative
      breast lesions (NPBL) is still debated. Sampling error and heterogeneity of
      breast lesions complicates the histologic correlation of fine-needle aspiration
      results further. METHODS: To provide optimal cytohistologic correlation, two
      smears (one that was stained with hematoxylin and eosin and one that was stained
      with Diff-Quik [American Scientific Products, McGraw Park, IL]) were prepared
      from specific tissue sections from breast biopsies without mass lesions. The 42
      cases classified as NPBL histologically were included in the current study. The
      cytologic features of the smears were evaluated. RESULTS: Cellularity ranged from
      low (40% of cases) to moderate (50% of cases) to high (7% of cases). The cells
      were arranged in small clusters in 79% of cases, were mixed with large sheets in
      17% of cases, and were in large sheets in 2% of cases. Intact lobules were noted
      in 31%. The configuration of the epithelial groups was complex in 62% of cases.
      Myoepithelial cells in the background and within the epithelial groups were noted
      in all the specimens. The percentage of single epithelial cells was < 10 in 38%
      of cases, 10-20 in 41%, and 20-30 in 19%. Mild nuclear enlargement and overlap,
      micronucleoli, and mild chromatin clumping were noted in a significant number of
      cases. CONCLUSIONS: NPBL have been found to have a wide spectrum of cytologic
      appearances. At one end of the spectrum, smears are cellular with up to 30%
      single cells and large sheets in a complex configuration and exhibit nuclear
      enlargement and overlap and prominent nucleoli, features that overlap with those
      described in proliferative breast lesions.

PMID- 11309781
TI  - A comparison of aspiration cytology and core needle biopsy in the evaluation of
      breast lesions.
AB  - BACKGROUND: Several arguments are used for choosing either fine-needle aspiration
      cytology (FNAC) or core needle biopsy (CNB) in the evaluation of breast lesions.
      Comparison of published data on both methods is complicated by differences in
      study design, calculations, and operator experience. The objective of this study
      was to make a direct comparison of both methods. METHODS: In 286 breast lesions
      (cysts and microcalcifications without a soft tissue mass excluded), both
      ultrasound-guided FNAC and CNB were performed in the same session by the same
      operator. Histologic follow-up was collected, and for those lesions that were not
      excised the results of the most recent mammography was used. A combination of the
      findings of both FNAC and CNB were evaluated. RESULTS: Core needle biopsy and
      FNAC do equally well for sensitivity (88% vs. 92%), positive predictive value for
      malignancy (99% vs. 100%), and inadequate rate (7% vs. 7%). However, statistical
      differences are found for the specificity (CNB, 90%; FNAC, 82%). In addition,
      differences are found in the positive predictive value of both suspicious (CNB,
      100%; FNAC, 78%) and atypia (CNB, 80%; FNAC, 18%) and for the suspicious rate
      (CNB, 5%; FNAC, 13%) reflecting difficulties in interpreting some FNACs.
      Combining the findings of both FNAC and CNB results in an increase in absolute
      sensitivity, a decrease in the positive predictive value of atypia compared with
      FNAC and CNB per se, and a decrease in the inadequate rate for cancers.
      CONCLUSIONS: For the lesions selected in this study, FNAC and CNB are comparable
      for most parameters, but CNB has a higher specificity and lower suspicious rate.
      Combining results of FNAC and CNB leads to an increase in absolute sensitivity
      without affecting specificity and a decrease in the inadequate rate for cancers.

PMID- 11309782
TI  - Fine-needle aspiration biopsy of peripheral T-cell lymphomas. A cytologic and
      immunophenotypic study of 33 cases.
AB  - INTRODUCTION: Peripheral T-cell lymphoma (PTCL) accounts for 10-20% of all non
      Hodgkin lymphomas in the United States. In this study, the authors reviewed the
      cytologic and immunophenotypic findings of 33 fine-needle aspirations (FNAs) of
      PTCL. METHODS: Thirty-three FNAs from 26 patients (12 females and 14 males) with
      PTCL were identified during 1991-1999. The patients' age ranged from 19 to 96
      years. Immunophenotyping was performed in 24 cases by using either flow cytometry
      (FC; 21 cases) or immunocytochemistry (IC; 3 cases). Follow-up included review of
      prior or current histology and clinical records. RESULTS: Nine cases were
      associated with mycosis fungoides, three cases were classified as T-cell chronic
      lymphocytic leukemia, and two were angioimmunoblastic adenopathy (AILD)-like T
      cell lymphoma. The remaining 19 were classified as PTCL, not otherwise specified.
      The latter consisted of eight mixed cell variant, eight large cell variant, and
      three anaplastic variant. One of the mixed cell variant and one of the large cell
      variants contained numerous epithelioid histiocytes (Lennert lymphoma). Thirty
      (91%) cases had a definitive diagnosis of malignant lymphoma. Twenty-two cases (2
      IC and 20 FC) showed a predominant population of T lymphocytes without a
      monoclonal B-cell population. In addition, FC revealed an aberrant expression of
      T-cell markers in 13 cases. Two cases were interpreted as "atypical lymphoid
      population"; one case was an AILD-like T-cell lymphoma, and the other case was
      PTCL, large cell type. One case initially was interpreted as granulomatous
      lymphadenitis; subsequent biopsy revealed PTCL, Lennert type. CONCLUSIONS:
      Peripheral T-cell lymphoma is a heterogeneous group of lesions with diverse
      cytomorphology. Cytologic analysis and immunophenotyping is an accurate method of
      diagnosing peripheral T-cell lymphoma.

PMID- 11309783
TI  - DNA image cytometry in the differential diagnosis of endocervical adenocarcinoma.
AB  - BACKGROUND: The value of DNA image cytometry in the differential diagnosis of
      endocervical adenocarcinoma was tested on a series of 65 cases of normal
      endocervical cells (n = 25), inflammatory changes (n = 18), and endocervical
      adenocarcinoma (n = 22). METHODS: The investigation was performed on gynecologic
      routine smears by using a television image analysis system MIAMED-DNA (Leica,
      Wetzlar, Germany), combined with an automated Leica Medilux microscope. First,
      the Papanicolaou stained specimens were rescreened, and the x/y coordinates of at
      least 150 endocervical nuclei were stored per case by using a scanning program.
      After restaining according to Feulgen, the epithelial cells were relocalized and
      the DNA content, and the nuclear area were determined. The DNA content of 25-30
      squamous epithelial cells of intermediate type served as an internal standard for
      the normal diploid value in each case. Various DNA cytometric parameters and the
      mean nuclear area were calculated. For statistical analysis, the cases of
      adenocarcinoma (n = 22) were defined as positive, and the cases with normal
      endocervical epithelium or inflammatory changes (n = 43) were defined as
      negative. RESULTS: The presence of nuclei with a DNA content greater than 9c was
      observed exclusively in adenocarcinoma (sensitivity, 95.9%; specificity, 100%),
      indicating that this parameter is suited best for the differentiation between
      malignant and nonmalignant endocervical epithelium. High sensitivity rates at a
      specificity level of 100% also were calculated for the 2.5cER (95.5%), the mean
      ploidy (90.9%), 5cER (90.9%), and the diploid deviation quotient (90.9%). For the
      2cDI (86.4%), the entropy (81.8%) and the ploidy imbalance (77.3%) lower values
      were obtained. CONCLUSIONS: DNA single cell cytometry represents a highly
      relevant tool in the identification of malignant transformation in endocervical
      lesions that could be used as a complementary diagnostic method in cytologically
      difficult cases. Investigations on endocervical adenocarcinoma in situ should be
      performed in the near future.

PMID- 11309784
TI  - Clinicopathologic analysis of breast carcinoma with chromosomal aneusomy detected
      by fluorescence in situ hybridization.
AB  - BACKGROUND: The clinicopathologic characteristics of breast carcinoma with
      chromosomal aneusomy detected by fluorescence in situ hybridization (FISH) have
      yet to be clarified. METHODS: Fine-needle aspiration biopsy (FNAB) samples were
      obtained from 113 breast tumors and were subjected to FISH analysis using
      centromeric probes for chromosomes 1, 11, and 17 to study a numerical aberration
      of these chromosomes and its correlation with various clinicopathologic features
      of breast tumors. RESULTS: Polysomy was observed in 77.0%, 50.5%, and 37.2% of
      breast carcinoma samples for chromosomes 1, 11, and 17, respectively, and
      monosomy was observed in 1.8%, 8.8%, and 22.1% for chromosomes 1, 11, and 17,
      respectively. High histologic grade showed a significant correlation (P < 0.05)
      with polysomy of chromosome 11. Lymph node metastasis showed a significant
      correlation (P < 0.05) with polysomy of all three chromosomes, and positivity of
      lymph node metastasis increased as the number of polysomic chromosomes increased.
      In addition, estrogen receptor negativity was correlated significantly (P < 0.05)
      with monosomy of chromosome 17, and progesterone receptor negativity was
      correlated significantly (P < 0.05) with polysomy of chromosomes 11 and 17.
      CONCLUSIONS: Aneusomy of chromosome 1, 11, or 17 detected by FISH is correlated
      significantly with various clinicopathologic features of breast carcinoma.
      Because FISH analysis of chromosomal aneusomy can be done using FNAB samples,
      this technique seems to have the potential to be used for a better, preoperative
      definition of the biologic characteristics of breast tumors.

PMID- 11309785
TI  - A hydroxyapatite coating covalently linked onto a silicone implant material.
AB  - A novel composite consisting of hydroxyapatite (HAp) microparticles covalently
      coupled onto a silicone sheet was developed. Initially, an acrylic acid (AAc) 
      grafted silicone sheet with a 16.7 microg/cm(2) surface graft density was
      prepared by corona-discharge treatment. The surface of sintered, spherical,
      carbonated HAp particles with an average diameter of 2.0 microm was subsequently
      modified with amino groups. The amino group surface density of the HAp particles
      was calculated to be approximately one amino molecule per 1.0 nm(2) of particle
      surface area. These samples were characterized with Fourier transform infrared
      spectrometry and X-ray photoelectron spectroscopy. After the formation of
      ammonium ionic bonds between both samples under aqueous conditions, they were
      reacted at 180 degrees C for 6 h in vacuo to form covalent bonds through a solid
      phase condensation. The HAp particles were coupled to the AAc-grafted silicone
      surface by a covalent linkage. Further improvements in the adhesive and bioactive
      properties of the HAp-coated silicone material are expected.

PMID- 11309786
TI  - Mechanical and histological evaluations of hydroxyapatite-coated and noncoated
      Ti6Al4V implants in tibia bone.
AB  - This paper evaluates the behavior of hydroxyapatite (HAP) coated and noncoated
      Ti6Al4V implants in dog tibia after 3 and 5 months implantation. HPA-coated
      implants were obtained by plasma spraying. XRD, SEM, and EPMA were employed to
      estimate the coating characteristics and their behavior in vivo. Investigation of
      material characteristics showed that the as-received coatings consisted mainly of
      amorphism and HAP phase. Other phases such as TCP and CaO were identified due to
      thermal changes of HAP particles in plasma flame. SEM micrographs showed a
      typical microstructure of plasma-sprayed coating. The as-received coating was
      formed by well-melted pancake-like splats that lead to a dense coating with a
      rough surface. Lamellar structure, micropores, and microcracks, observed inside
      the coating, are characteristic of plasma spraying. Push-out tests revealed that
      HAP coating had a significant promotion of interfacial shear strength. The shear
      strength between bone and HAP-coated implants was much higher than that between
      bone and noncoated implants due to the different bone-implant interfaces formed
      after implantation. SEM observation revealed a direct attachment between HAP
      coating and newly formed bone. However, noncoated implants were separated from
      newly formed bone by fibrous tissues. Ti ions were found to be released into the
      surrounding environment after long time immersion in body fluid, and thus caused
      low shear strength. Prolongation of implantation time had different effects on
      shear strength. It improved the shear strength between HAP-coated implant and
      newly formed bone. However, it had little effect on that between noncoated
      implant and surrounding tissues.

PMID- 11309787
TI  - Calcification resistance, biostability, and low immunogenic potential of porcine
      heart valves modified by dye-mediated photooxidation.
AB  - The calcification potential, biostability, and immunogenic response of materials
      intended for long-term in vivo use, such as in heart-valve bioprostheses, are
      essential components of device performance. Here we explore these properties in
      photooxidized porcine heart valves. To study immunological sensitization, we
      injected tissue extracts intradermally into guinea pigs. Test and control animals
      received a challenge patch of the appropriate extract and were scored for dermal
      reactions. Neither cottonseed oil nor sodium chloride extracts of photooxidized
      heart-valve tissues caused any dermal inflammatory response. After implantation
      in the rat subcutaneous model for 90 days, the calcium content of 48-h-treated
      photooxidized cusp tissue [0.04 +/- 0.00 mg/g wet weight (gww)] was comparable to
      that of unimplanted control tissues (usually <1 mg/gww) and much lower than that
      of glutaraldehyde-treated controls (71 +/- 15 mg/gww). The porcine aortic wall
      calcium content (49 +/- 31 mg/gww) was comparable to that of glutaraldehyde
      treated controls (59 +/- 8 mg/gww). Histologically, a time-dependent decrease in
      inflammation and vascularization with increasing photooxidation time was noted in
      the rat model along with an increase in the stability and organization of
      collagen bundles. In summary, porcine valve tissues treated by dye-mediated
      photooxidation were resistant to calcification, were biostable, and demonstrated
      a low immunogenic response, indicating potential for use in heart-valve
      bioprostheses.

PMID- 11309788
TI  - Biocompatibility of NDGA-polymerized collagen fibers. I. Evaluation of
      cytotoxicity with tendon fibroblasts in vitro.
AB  - The material properties of tendon type I collagen fibers polymerized with
      nordihydroguaiaretic acid (NDGA) are equivalent to native tendon, suggesting that
      NDGA crosslinking may provide a viable approach to stabilizing collagenous
      materials for repairing ruptured, lacerated, or surgically transected fibrous
      tissues, such as tendon and ligament (Koob & Hernandez, Biomaterials, in press).
      Using standard cytotoxicity tests, the present study evaluated the
      biocompatibility of these fibers with cultured bovine tendon fibroblasts. Primary
      fibroblasts obtained from calf digital extensor tendons were exposed to NDGA,
      reaction products generated from the polymerization protocol, and the crosslinked
      fibers. NDGA was cytotoxic to these cells at concentrations above 100 microM.
      NDGA oxidation products were similarly cytotoxic. At concentrations below 100
      microM, fibroblast viability was not affected by NDGA or its oxidation products.
      At these lower concentrations, fibroblast proliferation was unaffected compared
      to controls not exposed to NDGA. Fibers crosslinked with NDGA contained no
      unreacted NDGA, but they did contain soluble reaction products that were
      cytotoxic to tendon fibroblasts in both the elution and the direct contact tests.
      Washing the fibers in 70% ethanol and phosphate-buffered saline eliminated
      cytotoxicity of the fibers. Ethanol simultaneously sterilized the fibers. Tensile
      tests established that the ethanol/phosphate buffer wash did not adversely affect
      the material properties of the fibers. The results of these experiments indicate
      that NDGA-crosslinked fibers can be rendered nontoxic to tendon fibroblasts and
      may provide a novel approach for producing biologically based, biocompatible,
      tendon bioprostheses.

PMID- 11309789
TI  - Biocompatibility of NDGA-polymerized collagen fibers. II. Attachment,
      proliferation, and migration of tendon fibroblasts in vitro.
AB  - The material properties of collagen fibers polymerized with nordihydroguaiaretic
      acid (NDGA) are equivalent to native tendon, suggesting that NDGA crosslinking
      may provide a viable approach to stabilizing collagenous materials for use in
      repairing ruptured, lacerated, or surgically transected fibrous tissues, such as
      tendons and ligaments (Koob & Hernandez, Biomaterials, in press). The present
      study evaluated the biocompatibility of these fibers with cultured bovine tendon
      fibroblasts. Fibroblast attachment, migration, and proliferation on NDGA
      crosslinked materials were compared to those on prepolymerized type I tendon
      collagen constructs as well as on tissue-culture-treated plastic. Fibroblast
      attachment on NDGA-crosslinked collagen fibrils was equivalent to attachment on
      plates coated with collagen alone. Over a period of 8 days in culture, attached
      fibroblasts proliferated on NDGA-crosslinked collagen at a rate identical to that
      of fibroblasts attached to native collagen. In order for the biomaterial
      effectively to bridge gaps in fibrous tissues, fibroblasts must be able to
      migrate and replicate on the bridging fiber. Control and crosslinked fibers were
      inserted in calf tendon explants, with a portion of the fiber extending out of
      the sectioned end of the tendon. Explants were cultured for 9 weeks, and the
      number of cells was measured at weekly intervals. Cells appeared on the fibers
      after 1 week of culture. By 2 weeks, cells had colonized the entire fiber. The
      number of cells continued to increase throughout the 9 weeks in culture, forming
      a layer several cells thick. Histologic analysis indicated that the fibroblasts
      populating the fibers appeared to originate in the epitenon. There was no
      difference in the rate of fibroblast migration and replication, nor in the
      ultimate number of colonizing cells, between control collagen fibers and NDGA
      crosslinked fibers. NDGA-crosslinked fibers may provide a means of bridging gaps
      in ruptured, lacerated, or surgically transected tendons by providing a
      mechanically competent scaffold on which tendon fibroblasts can migrate, attach,
      and proliferate.

PMID- 11309790
TI  - Phase transitions of hydroxyapatite coatings during post-heat treatment and their
      performances under ultrasonic tests.
AB  - Highly or completely crystalline hydroxyapatite (HA) coatings can be obtained by
      post-heat treatment. We have developed a high-temperature (490 degrees C) and a
      low-temperature (125 degrees C) heat treatment to improve the crystallinity of HA
      coatings. Both methods transform entirely the amorphous phase into crystalline
      HA. However, the microstructure of the coating is dependent on the post-heating
      method. Nanocrystalline HA is about half of the component of the low-temperature
      heated coating while highly crystalline HA dominates the high-temperature heated
      coating, as detected by X-ray diffraction. The effects of both methods on the
      disintegration of the coatings were tested by ultrasonic treatment. The high
      temperature heated coatings exhibited poor integrity while the low-temperature
      heated coatings exhibited better integrity, possibly due to their different
      microstructure. SEM revealed that the coatings disintegrated via different
      mechanisms: the high-temperature heated coatings failed via crack initiation and
      propagation while the low-temperature heated coatings failed via pit formation
      and subsequent widening.

PMID- 11309791
TI  - Diamine extension of glutaraldehyde crosslinks mitigates bioprosthetic aortic
      wall calcification in the sheep model.
AB  - We previously have been able to show that fixation at increasing concentrations
      of glutaraldehyde (GA) leads to mitigated rather than facilitated tissue
      calcification. The purpose of the present study was to introduce additional
      crosslinks and provide evidence that crosslink density may be an underlying
      inhibitory principle. Entire aortic roots were chosen to verify the concept on
      the challenging aortic wall tissue. Porcine aortic roots were crosslinked with
      0.2% GA, 3%GA, and 3% GA containing an interim step that introduced diamine
      bridges. Crosslink efficiency was determined on the basis of shrinkage
      temperature (SrT degrees ), resistance to protease digestion (RPD), residual
      amine analysis (RA), and tensile modulus (E(10)). Calcium levels, calcification
      patterns, and inflammation were assessed after 6 and 24 weeks of implantation in
      a sheep circulatory model. Crosslink efficiency in aortic wall tissue was
      moderately affected by increasing the fixative concentration from 0.2% GA to 3%
      GA (SrT degrees from 85.7 degrees +/- 0.3 degrees to 87.5 degrees +/- 0.3 degrees
      C, p < 0.002; RPD from 24.2 +/- 1.2 to 29.1 +/- 0.7%, p < 0.003; RA from 0.069 +/
      0.004 to 0.058 +/- 0.003 micromol/mg, p < 0.03, and E(10) from 1.9 +/- 0.11 to
      2.94 +/- 0.34 MPa, p < 0.01), but it was distinctly enhanced when diamine bridges
      were introduced (SrT degrees from 87.5 degrees +/- 0.3 degrees to 93.4 degrees +/
      0.3 degrees C, p << 0.0001; RPD from 29.1 +/- 0.7 to 68.4 +/- 1.8%, p << 0.0001;
      and E(10) from 2.94 +/- 0.34 to 6.80 +/- 0.61 MPa, p < 0.0003). Aortic wall
      calcification was reduced significantly by increasing the GA concentration from
      0.2 to 3% [37.8%, p = 0.076 (6 weeks) and 34.0%, p = 0.008 (24 weeks)] and
      further reduced by the introduction of additional diamine [84.0%, p = 0.006 (6
      weeks) and 29.8%, p = 0.037 (24 weeks)]. The combined effect of increased GA
      concentration plus an interim diamine step on aortic wall tissue resulted in a
      90% and 53.7% reduction of calcification after 6 weeks and 24 weeks,
      respectively. The correlation coefficients between calcification and SrT degrees,
      RDP, and E(10) was -0.9767, -0.9460, and -0.9740, respectively (6 weeks). The
      inflammatory host reaction regularly found in 0.2% fixed tissue was practically
      abolished through the introduction of diamine bridges. Our study demonstrated a
      distinct correlation between the mitigation of aortic wall calcification and
      three parameters used to assess crosslink density.

PMID- 11309792
TI  - Microwear phenomena of ultrahigh molecular weight polyethylene cups and debris
      morphology related to gamma radiation dose in simulator study.
AB  - Ultrahigh molecular weight polyethylene (PE) cups with 0, 2.5, 50, 100, and 150
      Mrad radiation treatments were run in a hip simulator for comparison of the
      microwear phenomena on the cup surfaces with the corresponding debris morphology.
      In general, the size and frequency of the PE surface fibrils and the size of the
      retrieved PE debris decreased with increasing radiation dose. The fibril size and
      shape on the cup surfaces were well correlated with the radiation dose. The
      fibrillar shape and size were found to be proportional to the square root of the
      radiation dose. However, the trend for size and shape factors of the wear debris
      related to the radiation dose was weak at best. Thus, the morphology of the PE
      fibrils on the cup surfaces was more sensitive to variations in the radiation
      dose than the actual wear debris. The wear response appeared to be a three-step
      process, which was dependent on the formation of surface nodules or ripples, the
      teasing out of surface fibrils, and the toughness of the PE matrix in releasing a
      wear fibril to form a debris particle. The tougher PE became with increasing
      radiation dose, the harder it was for the PE fibrils to break out into wear
      particles.

PMID- 11309793
TI  - The growth of chondrocytes into a fibronectin-coated biodegradable scaffold.
AB  - Porous scaffolds made from a biodegradable copolymer of trimethylene carbonate
      and glycolide were evaluated for tissue-engineered medical products. We examined
      the scaffold coated with cell adhesion protein and fibronectin and cultured under
      a dynamic mixing condition to enhance the growth of chondrocytes. Our hypothesis
      was that the combination of coating and dynamic mixing would be beneficial to the
      viability of the chondrocytic cells. Fibronectin was selected as the model
      protein because of its availability and routine assaying methods. Sterile samples
      of scaffolds of about 1 mm in thickness were coated with fibronectin at 37
      degrees C for 1.5 h. Four groups of scaffolds were used: uncoated static or
      dynamic, and coated static or dynamic. Scaffold samples were placed in either a
      Petri dish or a spinner flask (static vs. dynamic groups) after inoculation with
      rat chondrocytes of an initial cell density of 1.29 x 10(5) cell/mL. After 7, 14,
      21, and 28 days, each sample was fixed, embedded, and sectioned at 5 micro
      thickness. The sections were double-label immunostained using antibodies against
      cellular fibronectin synthesized by adherent cells as a measure of cell
      viability. A Hoechst 33258 nuclear stain was used to measure the number of cells
      attached to the scaffold at each time interval. The slides were examined using a
      fluorescence microscope to determine the cell ingrowth. At least 25
      fields/treatment group (except the 7 day group) were measured. The data showed
      that cell in-growths into the porous scaffolds were higher at all time periods
      for the coated dynamic group than those for the other three groups.

PMID- 11309794
TI  - Stimulation of epithelial tissue migration by certain porous topographies is
      independent of fluid flux.
AB  - A surface with columnar pores 0.1 or 0.4 microm in diameter is shown to have a
      novel effect on the migration of corneal epithelial tissue sheets; migration is
      stimulated in a nondirectional manner with respect to migration over a planar,
      nonporous surface (Dalton, Evans, McFarland, and Steele, J Biomed Mater Res
      1999;45:384-394; Steele, Johnson, McLean, Beumer, and Griesser, J Biomed Mater
      Res 2000;50:475-482). By blind-ending the pores, we show that this increase in
      tissue migration is not dependent on fluid flux through the pores and so appears
      to occur as a result of surface topography. From transmission electron
      micrographs, the migrating tissue appears to form either close contacts or focal
      adhesions at the edge of some pore channels; we speculate that this may provide a
      fulcrum for the enhanced migration. Scanning electron micrographs suggest that
      within tissue that migrates over the surfaces that contain blind-ended pores, the
      cells are more extensively spread than those in tissue migrating on a planar
      surface. The migration of disaggregated epithelial cells is enhanced on surfaces
      that contain 0.1- or 0.4-microm-diameter pores (compared with a planar surface),
      and this is similarly independent of fluid flux.

PMID- 11309795
TI  - Cytotoxicity and immunogenicity of SACCHACHITIN and its mechanism of action on
      skin wound healing.
AB  - SACCHACHITIN membrane, a weavable skin substitute made from the residual fruiting
      body of Ganoderma tsugae, has been demonstrated to promote skin wound healing.
      Prior to its clinical application, it is critical to learn more about any
      possible cytotoxicity, immunogenicity, or allergy response, and at least some of
      its mechanism(s) of action(s). In the present studies, it has been found that
      SACCHACHITIN suspension at less than 0.05% shows no cytotoxicity to the primary
      culture of rat fibroblasts. However, at higher concentrations (> or = 0.1%), it
      does reduce the growth of fibroblasts, based on MTT assays. This might be caused
      by positive charges on chitin molecules that are too strong, and may be harmful
      to the cell membrane. SACCHACHITIN showed no immunogenicity after it was
      inoculated into rats three times; however, the unmodified, purified rabbit type I
      and type II collagens did. Subcutaneous injection of SACCHACHITIN suspension into
      rats showed no gross allergic responses on skin. Nevertheless, it did cause local
      acute inflammation, as observed by histological investigation. This is similar to
      what occurred in the wound site covered with SACCHACHITIN membrane. The
      chemotactic effect of SACCHACHITIN was exhibited in both intact and wounded skin
      tissues. This may be one of the initial beneficial effects of SACCHACHITIN
      membrane to wound healing. The rapid acute inflammatory process was followed by
      the appearance of angiogenesis and granulation tissue formation, which occurred
      earlier than it normally would. Coverage of the wound area with SACCHACHITIN
      membrane also induced an earlier formation of scar tissue to replace the
      granulation tissue. A 1.5 x 1.5 cm(2) wound area covered by SACCHACHITIN
      completely healed by 21 days, while that covered with cotton gauze did not.
      Therefore, SACCHACHITIN is a safe biomaterial for use as a wound dressing for
      skin healing. Its promoting action for wound healing might be due to its
      chemotactic effect for inflammatory cells. This, in turn, may facilitate
      subsequent angiogenesis, granulation tissue formation, and faster new tissue
      formation, leading to faster wound healing.

PMID- 11309796
TI  - Effects of carbodiimide crosslinking conditions on the physical properties of
      laminated intestinal submucosa.
AB  - Functional tissue engineering of load-bearing repair tissues requires the design
      and production of biomaterials that provide a remodelable scaffold for host
      infiltration and tissue regeneration while maintaining the repair function
      throughout the remodeling process. Layered constructs have been fabricated from
      chemically and mechanically cleaned porcine intestinal collagen using ethyl-3(3
      dimethylamino) propyl carbodiimide (EDC) and an acetone solvent. By varying the
      concentration of the crosslinker from 1 to 10 mM and the solvent from 0 to 90%
      acetone, the strength, stiffness, maximum strain, thermal stability, lamination
      strength, and suture retention strength can be adjusted. These parameters have
      either functional importance or the potential to modify the remodeling kinetics,
      or they have both. This study investigates the interdependence of these
      parameters, the specific effects that variations in concentration can achieve,
      and how the two crosslinking variables interact. The results demonstrate that
      there is substantial latitude in the design of these constructs by these
      straightforward crosslinking modifications. These data provide the basis for
      studying the in vivo response to crosslinking conditions that will supply the
      requisite strength while still allowing host cell infiltration and remodeling.

PMID- 11309797
TI  - Surface enhancements accelerate bone bonding to CPC-coated strain gauges.
AB  - Calcium phosphate ceramic (CPC)-coated strain gauges have been used for in vivo
      bone strain measurements for up to 18 weeks, but they require 6 to 9 weeks for
      sufficient bonding. Osteogenic protein-1 (OP-1), PepTite (a proprietary ligand),
      calcium sulfate dihydrate (CSD), transforming growth factor beta-1 (TGF-beta1 ),
      and an endothelial cell layer with and without TGF-beta1 were used as surface
      enhancements to accelerate bone-to-CPC bonding. Young male Sprague-Dawley rats
      were implanted with unenhanced and enhanced CPC-coated gauges. Animals were
      allowed normal activity for 3 weeks and then calcein labeled. Femurs were
      explanted following euthanasia. A gauge was attached with cyanoacrylate to the
      opposite femur in the same position as the CPC-coated gauge. Bones were
      cantilever-loaded to assess strain transfer. They were sectioned and stained with
      mineralized bone stain (MIBS) and examined with transmitted and ultraviolet
      light. Mechanical testing indicated increased sensing accuracy for TGF-beta1 and
      OP-1 enhancements to 105 +/- 14% and 92 +/- 12% versus 52 +/- 44% for the
      unenhanced gauges. The PepTite and the endothelial-cell-layer-enhanced gauges
      showed lower sensing accuracy, and histology revealed a vascular layer near CPC
      particles. TGF-beta1 increased bone formation when used prior to endothelial cell
      sodding. CSD prevented strain transfer to the femur. TGF-beta1 and OP-1 surface
      enhancements produced accurate in vivo strain sensing on the rat femur after 3
      weeks.

PMID- 11309798
TI  - Biocompatible hydrogel supports the growth of respiratory epithelial cells:
      possibilities in tracheal tissue engineering.
AB  - Extensive tracheal defect reconstruction is a major challenge in plastic and
      reconstructive surgery. The lack of an epithelial lining on the luminal surfaces
      of tracheal prostheses is among the major causes of their failure. Chitosan
      gelatin hydrogels were synthesized for the development of biocompatible, growth
      supportive substrata for respiratory epithelial cells. We employed J774
      macrophages to test the immunocompatibility of this gel. The hydrogel did not
      exert a cytotoxic effect on macrophages, as confirmed by tetrazolium reduction
      and neutral red uptake assay. Flow cytometric analysis of macrophages cultured on
      the hydrogel showed a comparable expression of activation markers CD11b/CD18,
      CD45, and CD14 to the control. Semiquantitative RT-PCR results showed an absence
      of upregulation of interleukin-6 (IL-6) and TNF-alpha in these macrophages with
      respect to the controls. Primary human respiratory epithelial cells cultured on
      the hydrogel showed proper attachment, normal morphology, and growth. A small
      proportion of cells on the hydrogel showed synchronously beating cilia. RT-PCR
      analysis showed that cells on the hydrogel expressed mucins 2 and 5 and
      cytokeratin 13, which are markers for secretory goblet and squamous cells,
      respectively. All these results demonstrate that the hydrogel supports the growth
      of a mixed population of differentiated epithelial cells. This hydrogel is
      suitable as a culture substratum for respiratory epithelial cells and could be
      used as a potential candidate for coating tracheal prostheses.

PMID- 11309799
TI  - Enhancement of bone regeneration using resorbable ceramics and a polymer-ceramic
      composite material.
AB  - The aim of this experimental study was to evaluate the use of resorbable implants
      for the repair of nonloaded skeletal defects. Porous ceramic implants of alpha
      TCP, of glass-ceramic, and of solid composite implants of glass
      ceramic/polylactic acid 8 mm in diameter and 2 mm in thickness were fabricated
      and implanted pressfit into biparietal, full-thickness defects of the calvaria of
      60 adult rats. Twenty rats received unfilled defects and served as controls.
      Fluorochrome labeling of bone formation was performed during the observation
      period. Five animals from each group were evaluated after 6, 13, 26, and 52
      weeks. The control defects showed incomplete regeneration, with bone formation
      extending 1.66 mm, on average, into the defect after 52 weeks. In the group of
      alpha-TCP implants, histologic evaluation indicated that the bone formed during
      initial stages had undergone resorption later on, so that bone repair after 52
      weeks was not significantly enhanced, with an average depth of 1.83 mm of bone
      ingrowth. The glass-ceramic implants exhibited extensive bone formation and
      nearly complete repair of the calvarial defect, with 3.90 mm of bone ingrowth
      into the implant pores. Degradation of the ceramic was nearly complete, with a
      few remaining particles surrounded by soft tissue. The composite implants showed
      a negligible bone ingrowth of 0.63 mm, on average. Soft tissue had invaded the
      polylactic acid implant body, but no bone formation had taken place at the
      surface of the embedded ceramic particles. Degradation of the polymer was not
      complete after 52 weeks. It is concluded that the balance between degradation and
      bone formation is delicate and that chemical events and cellular reaction during
      degradation may counteract complementary bone ingrowth.

PMID- 11309800
TI  - The fixation properties of carbon fiber-reinforced liquid crystalline polymer
      implant in bone: an experimental study in rabbits.
AB  - A novel composite material with ultra-high strength and a low elastic modulus
      called carbon fiber-reinforced liquid crystalline polymer (LCP/CF) has been
      developed. We studied the fixation properties of an intramedullary LCP/CF rod in
      rabbit bone. The medullary canals of both femora were reamed with a drill 3.2 mm
      in diameter starting from the trochanteric fossa in eleven New Zealand White
      rabbits weighing on average 4.8 kg. A smooth LCP/CF rod 3.2 mm in diameter and 50
      mm in length was introduced into the medullary canal of both femora. The follow
      up intervals were 0, 6, 12, and 52 weeks. The upper part of the harvested femora
      was cut into two pieces, each 25 mm in length. A mechanical push-out test was
      performed within 48 h to determine bone-implant interface attachment strength in
      the proximal (cancellous) and distal (cortical) locations. The mean push-out
      strength values at 0, 6, 12, and 52 weeks were 61, 250, 382, and 612 KPa in the
      cancellous location and 0, 32, 41, and 68 KPa in the cortical location,
      respectively. The strength of the bone/implant interface appeared to be quite
      low, similar to other uncoated or nonporous implants, but it was found to
      increase with time.

PMID- 11309801
TI  - Studies on the effect of virtual crosslinking on the hydrolytic stability of
      novel aliphatic polyurethane ureas for blood contact applications.
AB  - The effect of virtual crosslinking on the hydrolytic stability of completely
      aliphatic novel poly(urethane ureas), HFL9-PU1 (hard-segment content 57.5%) and
      HFL13-PU2 (hard-segment content 67.9%) based on 4,4'-methylene bis(cyclohexyl
      isocyanate) (H(12)MDI)-hydroxy-terminated polybutadiene-1,6-hexamethylene
      diamine, was studied. Fourier transform infrared-attenuated total reflectance and
      wide-angle X-ray diffraction studies revealed hydrogen-bonding interaction and
      microphase separation and formation of crystallites by short- and long-range
      ordering in hard-segment domains. Three-dimensional networks from hydrogen
      bonding in the present polymers lead to virtually crosslinking and insolubility.
      These polymers were noncytotoxic to L929 fibroblast cells. The hemolytic
      potential is below the accepted limit. The studies on in vitro biostability in
      Ringer's solution, phosphate buffered saline, and papain enzyme revealed no
      weight loss. The infrared spectral studies revealed changes in the surface,
      especially on HFL9-PU1 aged in Ringer's solution and phosphate buffered saline,
      and no changes when aged in papain. The marginal changes noticed in tensile
      properties were attributed to the changes in degree of hydrogen bonding and
      associated rearrangement of molecular structure in the bulk. The results revealed
      that the lesser the crosslinking in virgin polymer, the higher the crosslinking
      in aged polymer and vice versa. Increased crosslinking during aging provided
      increased tensile properties in the aged polymer over the virgin polymer and vice
      versa. For comparison, an aliphatic polyetherurethane urea (HFL16-PU3) was also
      synthesized using poly(oxy tetra methylene glycol) in addition to the above
      reactants. Though both HFL9-PU1 and HFL16-PU3 contained the same hard-segment
      content, the aged sample of the latter showed decreased tensile properties with
      increased crosslinking during aging in contrast to the former. This was
      attributed to less microphase separation in the virgin HFL16-PU3 polymer.

PMID- 11309802
TI  - Monitoring of in vitro and in vivo translation of green fluorescent protein and
      its fusion proteins by fluorescence correlation spectroscopy.
AB  - BACKGROUND: Because the process of protein translation is an event of sparse
      molecules, the measurement requires high sensitivity. One of the candidates for
      studying the molecules is fluorescence correlation spectroscopy (FCS), which
      gleans quantitative information from fluctuating fluorescence signals in a
      diluted solution. METHODS: Using FCS, the translation products of expression
      plasmid for green fluorescent protein (GFP) and its fusion proteins were measured
      in vitro and in vivo. RESULTS: In in vitro translation, the number of products
      increased linearly for 90 min upon concentration of the plasmid. The
      autocorrelation function for GFP was fitted with a one-component model with a
      diffusion time of 0.18 ms, which was identical to the value expected from the
      molecular weight. In the cases of GFP- tagged hypoxia-inducible factor-1 alpha
      and glucocorticoid receptor, each fitting result was significantly improved with
      a two-component model. The slow component with a diffusion time of 6 ms appeared
      to be related to the ribosome or polysome. In response to the addition of
      dexamethasone, the nuclear translocation from cytosol clearly induced the
      decrease in number of molecules in the focal point. CONCLUSIONS: FCS permits
      monitoring of the number of molecules translated in vitro and in vivo, the
      translation rate, and the molecular weight.

PMID- 11309803
TI  - New concepts to improve resolution and sensitivity of molecular cytogenetic
      diagnostics by multicolor fluorescence in situ hybridization.
AB  - BACKGROUND: Routine application of multicolor fluorescence in situ hybridization
      (M-FISH) technology for molecular cytogenetic diagnostics has been hampered by
      several technical limitations. First, when using chromosome-specific painting
      probes, there is a limit in cytogenetic resolution of approximately 2-3 Mb, which
      can mask hidden structural abnormalities that have a significant clinical effect.
      Second, using whole chromosome painting probes, intrachromosomal rearrangements
      cannot be detected and the exact localization of breakpoints is often not
      possible. METHODS: We suggest the use of multiplex-labeled region or locus-
      specific probes in combination with an optimal probe design to improve the
      sensitivity and resolution of the M-FISH technology. To allow the application of
      this assay in routine diagnostics, we developed a multipurpose image analysis
      system. RESULTS: goldFISH was applied to the study of cryptic translocations in
      mental retardation patients and to the study of high-resolution breakpoint
      mapping in non-small cell lung cancer patients. For an individual with mental
      retardation, who had an apparently normal karyotype by G-banding, we detected an
      unbalanced translocation involving chromosomes 2 and 7. CONCLUSIONS: In
      combination with optimally designed probe kits, goldFISH overcomes most of the
      present limitations of the M-FISH technology and results in virtually 100%
      reliability for detecting interchromosomal and intrachromosomal rearrangements.

PMID- 11309804
TI  - Cryptomonad algal phycobiliproteins as fluorochromes for extracellular and
      intracellular antigen detection by flow cytometry.
AB  - BACKGROUND: Phycobiliproteins play an important role in fluorescent labeling,
      particularly for flow cytometry. The spectral properties of R-phycoerythrin (R
      PE) and allophycocyanin (APC) have made them the dominant reagents in this class
      of fluorochromes. In this study, we evaluate a lesser-known but potentially
      important series of low-molecular weight cryptomonad-derived phycobiliproteins
      (commercially termed the CryptoFluortrade mark dyes) for their applicability to
      flow cytometry, both in extracellular and intracellular labeling applications.
      METHODS: Several cell lines were labeled with biotin-conjugated antibodies
      against expressed extracellular surface proteins, followed by streptavidin
      conjugates of three cryptomonad phycobiliproteins (CryptoFluor-2, CryptoFluor-4,
      and CryptoFluor-5). Cells were then analyzed by flow cytometry using a variety of
      laser lines and emission filters to establish the optimal excitation/emission
      characteristics for each fluorochrome. Some cells were permeabilized and labeled
      for intracellular antigens, also using the cryptomonad fluorochromes. Where
      appropriate, parallel samples were labeled with other fluorochromes (including R
      PE, APC, the cyanin dyes Cy3 and Cy5, and others) to gauge the performance of the
      cryptomonad fluorochromes against fluorescent labels previously evaluated for
      flow cytometry. RESULTS: CryptoFluor-2 possessed excitation/emission maxima
      similar to those of APC and Cy5, with good excitation in the red (HeNe laser 632
      nm) and strong emission in the far red (660 nm). CryptoFluor-4 possessed
      excitation/emission maxima similar to those of Cy3, with optimal excitation in
      the green (Kr 530 nm) and strong emission in the yellow/orange (585 nm).
      CryptoFluor-5 possessed excitation/emission maxima similar to those of lissamine
      rhodamine, with optimal excitation in the yellow (Kr 568 nm) and emission in the
      orange (610 nm). All cryptomonad fluorochromes gave satisfactory results for both
      intracellular and extracellular labeling, with detection sensitivities that were
      comparable or better than traditional phycobiliproteins and low- molecular weight
      synthetic fluorochromes such as the cyanin dyes. CONCLUSIONS: The CryptoFluor
      fluorochromes were applicable to flow cytometric immunodetection, with excitation
      and emission conditions commonly found on multilaser instruments. Performance of
      several of these dyes was at least comparable to existing fluorescent labels. The
      low molecular weights (30-60 kd) of phycobiliproteins may make them particularly
      useful in intracellular antigen detection. Cytometry 44:16-23, 2001. Published
      2001 Wiley-Liss, Inc.

PMID- 11309805
TI  - Phycoerythrin-allophycocyanin: a resonance energy transfer fluorochrome for
      immunofluorescence.
AB  - BACKGROUND: As immunofluorescence experiments become more complex, the demand for
      new dyes with different properties increases. Fluorescent dyes with large Stoke's
      shifts that are very bright and have low background binding to cells are
      especially desirable. We report on the properties of the resonance energy tandems
      of phycoerythrin and allophycocyanin (PE-APC). PE-APC is the original
      fluorescence resonance energy tandem dye described in the literature, but it has
      not been utilized because of the difficulty of synthesizing and preparing a
      consistent product. METHODS: PE-APC complexes comprising different ratios of the
      two phycobiliproteins conjugated to streptavidin were synthesized using standard
      protein-protein conjugation chemistry. The PE-APC streptavidins were evaluated
      for flow cytometric analysis. They were compared directly to Cy5PE conjugates
      because Cy5PE is the fluorophore that is spectrally most like the PE-APC.
      RESULTS: PE-APC complexes showed the expected fluorescence spectral properties of
      a tandem: excitation was excellent at 488 nm (and best at the PE excitation
      maximum) and emission was greatest at the APC emission maximum at about 660 nm.
      The efficiency of transfer of energy from PE to APC was about 90%. CONCLUSION: PE
      APC can be considered an excellent substitute for Cy5PE. Compared with Cy5PE, PE
      APC has similar brightness (in staining experiments), slightly greater
      compensation requirements with PE but much lower compensation with Cy5.5PE or
      Cy5.5PerCP, and lower nonspecific background binding. PE-APC is a useful
      alternative to Cy5PE, especially in applications in which the use of Cy5 is
      impractical. Cytometry 44:24-29, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11309806
TI  - Competitive antibody binding to soluble CD16B antigen and CD16B antigen on
      neutrophils in whole blood by flow cytometry.
AB  - BACKGROUND: Shed receptors from the surface of white blood cells in whole blood
      have been quantitated using the long and tedious enzyme-linked immunosorbent
      assay (ELISA) method. A simple rapid flow cytometric method of analysis for shed
      antigen in the presence of cell-bound antigen can be advantageous. METHODS:
      Magnetic bead depletion of neutrophils in whole blood with CD16b antibody
      conjugated beads as measured by flow cytometric analysis of the remaining cell
      suspension was inhibited by the presence of soluble CD16b antigen in the blood
      plasma of normal donors. We describe a competitive binding assay between labeled
      and unlabeled CD16b antibody for receptors shed from the surface of formed bodies
      (cells) into solution. Also presented is a new method of obtaining the amount of
      soluble antigen in a sample. We determine the total unlabeled and labeled ligand
      concentration at which the fluorescence intensity of the labeled ligand matches
      the fluorescence intensity in a control run with only the labeled ligand.
      RESULTS: Normal blood donors showed serum concentration levels of shed CD16b
      antigen in the range of 1-50 nM as determined by a flow cytometric competitive
      binding assay. These figures compared favorably with parallel determinations
      using magnetic bead depletion of targeted neutrophils for washed and unwashed
      whole blood samples to evaluate the concentration of shed CD16b antigen.
      CONCLUSIONS: The competitive antibody binding assay for shed and cell-bound CD16b
      antigen can be applied to similar GPI-linked antigens, for which purified
      antibody and fluorescent antibody against the same antigenic receptor are
      available.

PMID- 11309808
TI  - Early functional apoptotic responses of thymocytes induced by Tri-n-butyltin.
AB  - BACKGROUND: Programmed cell death, also termed apoptosis, is the main focus of
      interest in a variety of scientific and clinical areas. For a better
      understanding of the mechanisms of apoptosis, from the onset of the cellular
      death program to the late stages of apoptosis or apoptotic necrosis, very early
      functional events have to be quantified because they might be involved in
      temporal and causal relationships between apoptosis-related key processes.
      METHODS: We have established a flow cytometric technique to quantify time
      dependent signals simultaneously with high temporal resolution (Deltat = 1 s) in
      living cells. With this technique, the response of cells to apoptosis-stimulating
      agents can be analyzed over 15 min. For this purpose, a thermostatted sample tube
      holder for repeatable interruption-free injection of substances into the cell
      suspension was developed. Early detectable fluorescence and scatter parameters
      were related to intracellular free Ca2+ concentration, [Ca2+]i (Indo-1
      fluorometry), membrane permeability (propidium iodide [PI] influx), and cell
      volume (forward scatter). RESULTS: A T-cell line (Jurkat) served as a model
      system. Apoptosis was induced by the biozid Tri-n-butyltin (TBT). Dependent on
      the TBT concentration (0.3-10 microM), the mean free [Ca2+]i increased by a
      factor of 1.2-6 during a short time interval of just 2 min. Especially after low
      TBT concentrations (< 0.5 microM), this [Ca2+]i increase was nearly transient
      during the observation time of 15 min. Higher TBT concentrations (0.5-10 microM),
      however, induced a transient increase of [Ca2+]i (Ca-TR) only in a fraction of
      the cells; in another subpopulation, a steady-state Ca2+ signal (Ca-SST) was
      observed. The analysis of the simultaneously registered PI signals of the Ca-SST
      cells showed a shift to increasing PI fluorescence (by a factor of about 4) with
      increasing Ca2+ concentrations. In Ca-TR cells, the PI fluorescence remained
      nearly unchanged. These apoptosis-related changes (increase in [Ca(2+)]i and
      membrane permeability) could be confirmed by the additional observation of a TBT
      concentration-dependent decrease in cell volume measured during the same early
      time period. CONCLUSIONS: The simultaneously analyzed parameters (i.e., [Ca2+]i,
      membrane permeability, and cell volume) suggested that, in our model system of
      Jurkat T-cells treated with TBT, an apoptotic cell fate was indicated very early
      (within 15 min) by the steady-state [Ca2+]i level.

PMID- 11309807
TI  - Characterization of viable autofluorescent macrophages among cultured peripheral
      blood mononuclear cells.
AB  - BACKGROUND: Inflammatory macrophages that demonstrate intense autofluorescence
      have been isolated directly from alveolar and peritoneal tissues, but their
      generation in vitro remains vague. We use flow cytometry to identify a population
      of autofluorescent macrophages as they arise among nonadherent populations of
      cultured blood mononuclear cells. METHODS: Cells were obtained from donated blood
      buffy coats and placed in culture for 14 days. Unstained populations from the
      cells remaining in suspension were sampled daily using flow cytometry. During the
      first 5 culture days, a distinct population of autofluorescent cells arose and
      comprised an average of < or =14% of the total cell population. This population
      declined to less than 6% by culture day 8. RESULTS: The cells were identified as
      viable macrophages expressing CD68, lysozyme, and HLA-DR. Quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) demonstrated a unique cytokine
      profile with IL-1 alpha expression levels 138-fold higher than those measured in
      uncultured monocytes. No significant elevation in the levels of other cytokines
      was identified. Upon replating, the sorted populations became readherent, were
      able to ingest plastic beads, and remained viable for 6 or more additional weeks
      in culture without evidence of proliferation or multinucleation. CONCLUSION:
      Viable autofluorescent macrophage populations arising among cultured peripheral
      blood may be easily identified and isolated for further study using flow
      cytometry. Cytometry 44:38-44, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11309809
TI  - Supravital exposure to propidium iodide identifies apoptosis on adherent cells.
AB  - BACKGROUND: Several studies indicate that plasma membrane changes during
      apoptosis are a general phenomenon. Among the flow cytometric methods to measure
      apoptosis, the Annexin V assay that detects the membrane exposure of
      phosphatidylserine (PS) is one of the most commonly used. However, the various
      treatments used for the detachment of adherent cells generally interfere with the
      binding of Annexin V to membrane PS, making apoptosis measurement a technical
      problem. Materials and Methods Apoptosis of different cell lines was investigated
      by fluorescence microscopy and multiple flow assays designed to assess loss of
      membrane integrity, translocation of PS, DNA fragmentation, and light scatter
      changes. Results and Conclusions We show that supravital propidium iodide (PI)
      assay stains adherent apoptotic cells, allowing flow cytometric quantification.
      Moreover, supravital exposure to PI without prior permeabilization identifies
      apoptotic cells as well as Annexin V and permits the simultaneous surface
      staining by FITC- and PE-conjugated monoclonal antibodies. As in the case of
      necrotic or permeabilized cells, fluorescence microscopy has revealed that PI
      staining of apoptotic cells is localized in the nucleus. This suggests that the
      binding of PI to the DNA/RNA structures is stable enough to withstand the
      trypsinization and/or washing procedures necessary to detach adherent cells.

PMID- 11309810
TI  - Oncosis is associated with exposure of phosphatidylserine residues on the outside
      layer of the plasma membrane: a reconsideration of the specificity of the annexin
      V/propidium iodide assay.
AB  - BACKGROUND: Following a lethal injury, two modes of cell death can be
      distinguished, apoptosis and primary necrosis. Cells pass through a prelethal
      stage characterized by a preservation of membrane integrity, in which they shrink
      (apoptosis) or swell (oncosis, the early phase of primary necrosis). During
      apoptosis, a loss of phospholipid asymmetry leads to exposure of
      phosphatidylserine (PS) residues on the outer leaflet of the plasma membrane. We
      examined whether the external PS exposure, initially supposed to be specific for
      apoptosis, was also observed in oncotic cells. METHODS: Human peripheral
      lymphocytes, Jurkat T cells, U937 cells, or HeLa cells were submitted to either
      apoptotic or oncotic stimuli. PS external exposure was assessed after binding of
      FITC-conjugated annexin V as was the loss of membrane integrity after propidium
      iodide (PI) uptake. Morphological examination was performed by optical or
      electron microscopy. RESULTS: Similarly to apoptotic cells, oncotic cells expose
      external PS residues while preserving membrane integrity. Consequently, oncotic
      cells exhibit the annexin V+ PI- phenotype, previously considered to be specific
      for apoptotic cells. CONCLUSIONS: This study concludes that the annexin V/PI
      assay does not discriminate between apoptosis and oncosis and that it can be a
      useful tool to study oncosis by flow cytometry.

PMID- 11309812
TI  - High throughput flow cytometry.
AB  - BACKGROUND: Conventional flow cytometry does not allow the rapid analysis of
      multiple samples. This has limited its uses in drug discovery, for which the
      standard for throughput is 100,000 samples per day. METHODS: We describe a simple
      method in which commercial peristaltic tubing is connected from a commercial
      autosampler to a flow cytometer. The samples are delivered via a peristaltic pump
      from source wells in a multiwell plate. The samples are separated by air bubbles.
      RESULTS: Throughput rates approach the limit of the autosampler (up to 100 wells
      per minute). Using optimal tubing and flow rates, particles remain within
      appropriate light scatter and fluorescence gates. The carryover between wells is
      typically less than 5% without and 1% with a wash step. The volumes of sample
      delivered are in the microliter scale. The approach has been validated with
      instruments from three manufacturers. CONCLUSIONS: Flow cytometry has potential
      throughput of 100,000 samples or more per day starting with the method described.
      The method is currently best suited to end-point assays. However, combined with
      high-speed sorting and single- cell assays, the number of assays could approach 1
      billion per day.

PMID- 11309811
TI  - Detection of caspases activation by fluorochrome-labeled inhibitors:
      Multiparameter analysis by laser scanning cytometry.
AB  - BACKGROUND: The fluorochrome-labeled inhibitors of caspases (FLICA) were recently
      used as markers of activation of these enzymes in live cells during apoptosis
      (Bedner et al.: Exp Cell Res 259:308-313, 2000). The aims of this study were to
      (a) explore if FLICA can be used to study intracellular localization of caspases;
      (b) combine the detection of caspase activation with analysis of the changes with
      cell morphology detected by microscopy and laser scanning cytometry (LSC); and
      (c) adapt the assay to fixed cells that would enable correlation, by
      multiparameter analysis, of caspase activation with the cell attributes that
      require cell permeabilization in order to be measured. METHODS: Apoptosis of
      human MCF-7, U-937, or HL-60 cells was induced by camptothecin (CPT) or tumor
      necrosis factor-alpha (TNF-alpha) combined with cycloheximide (CHX). Binding of
      FLICA to apoptotic versus nonapoptotic cells was studied in live cells as well as
      following their fixation and counterstaining of DNA. Intensity of cell labeling
      with FLICA and DNA-specific fluorochromes was measured by LSC. RESULTS: Exposure
      of live cells to FLICA led to selective labeling of cells that had morphological
      changes characteristic of apoptosis. The FLICA labeling withstood cell fixation
      and permeabilization, which made it possible to stain DNA and measure its content
      for identification of the cell cycle position of labeled cells. When fixed cells
      were treated with FLICA, both apoptotic and nonapoptotic cells became strongly
      labeled and the labeling pattern was consistent with the localization of caspases
      as reported in the literature. A translocation of the FLICA binding targets from
      mitochondria to cytosol was seen in the MCF-7 cells treated with CPT. FLICA
      binding was largely (> 90%) prevented by the substrates of the caspases or by the
      unlabeled caspase inhibitors having the same peptide moiety as the respective
      FLICA. CONCLUSIONS: The detection of caspase activation combined with cell
      permeabilization requires exposure of live cells to FLICA followed by their
      fixation. Cell reactivity with the respective FLICA, under these conditions,
      identifies the activated caspases and makes it possible to correlate their
      activation with the cell cycle position and other cell attributes that can be
      measured only after cell fixation/permeabilization. FLICA can also be used to
      study intracellular localization of caspases, including their translocation.

PMID- 11309815
TI  - Measurement of MAP kinase activation by flow cytometry using phospho-specific
      antibodies to MEK and ERK: potential for pharmacodynamic monitoring of signal
      transduction inhibitors.
AB  - Cancer cells frequently show abnormal signaling via the mitogen activated protein
      kinase (MAP kinase) pathway due to increased activity of surface receptors for
      growth factors, or as a result of ras mutations. The development of potent anti
      cancer agents that target this pathway prompts the need for analytical methods
      that allow pharmacodynamic monitoring of drug effects in patients during early
      phase clinical trial. We describe such a method, based on the activation of T
      lymphocytes in undiluted peripheral blood using phorbol myristate acetate (PMA).
      Following rapid hypotonic lysis and formaldehyde fixation, activation of the MAP
      kinase pathway can then be demonstrated using phospho-specific antibodies that
      recognize the activated mediators MEK or ERK, followed by surface labeling with
      anti-CD3 to identify T-lymphocytes. This method was used to investigate the
      effects of a MEK inhibitor, U0126, and a new raf kinase inhibitor BAY 37-9751 in
      blood samples from normal donors. Dose-dependent inhibition of pERK activation
      was demonstrated for both agents. Furthermore, differential effects on pMEK
      activation allowed the molecular targets of the two inhibitors to be
      distinguished. In addition to monitoring drug effects in patients during
      treatment with inhibitors of the MAP kinase pathway, the general methodology
      described in this paper has the potential for wide application to the study of
      signal transduction at the single cell level using flow cytometry.

PMID- 11309816
TI  - DNA copy number amplifications in sarcomas with homogeneously staining regions
      and double minutes.
AB  - To identify DNA amplifications in sarcomas, comparative genomic hybridization was
      performed on 27 cases that were likely to display high-level DNA copy number
      gains. In all cases, chromosome banding analysis had revealed homogeneously
      staining regions or double minutes, i.e., cytogenetic signs of gene
      amplification. In most cases, gains predominated over losses. Low-level
      amplifications (ratio 1.3:1.5) were seen in 20 cases. High-level amplifications
      (ratio >1.5) exceeded the frequencies seen in published, unselected sarcomas of
      similar histotypes and were detected in 16 tumors: 4/4 osteosarcomas, 5/8
      malignant fibrous histiocytomas, 3/7 leiomyosarcomas, 1/2 myosarcomas, 0/1
      liposarcoma, 0/1 rhabdomyosarcoma, 1/1 pleomorphic sarcoma, 0/1 myxofibrosarcoma,
      1/1 malignant mesenchymona, and 1/1 malignant schwannoma, with two to four
      chromosomal regions involved in nine tumors. Recurrent amplifications involved
      1p33-p32, 5p15-p14, 7pter-p12, 7q21-qter, 8q21.3-qter, 11q22-q23, 16p13.2-p12,
      19q12-q13.1, 20q11.2-qter, and 22q12-q13. Most of the recurrent
      gains/amplifications we detected have been reported in sarcomas previously. A
      novel gain/amplification was seen at 2q14.3-q21 in five cases of four sarcoma
      types. The disparate pattern of amplified sequences, the poor correspondence
      between the localization of low- and high-level amplifications, and the
      chromosomal position of homogeneously staining regions suggest the involvement of
      many genes in the amplifications and that the genes rarely maintain their native
      position in these tumors.

PMID- 11309817
TI  - Comparative genomic hybridization study of nasal-type NK/T-cell lymphoma.
AB  - BACKGROUND: Nasal-type NK/T-cell lymphoma is a rare type of non-Hodgkin's
      lymphoma. The genetic changes associated with pathogenesis have not been well
      defined. This study investigates the nonrandom genetic alteration of nasal-type
      NK/T-cell lymphoma. METHODS: Nine cases were studied. Comparative genomic
      hybridization (CGH) was carried out using fresh tumor tissues of seven nasal-type
      NK/T-cell lymphomas. To complement the data by CGH, loss of heterozygosity (LOH)
      of chromosomes 6q, 1p, and 17p using polymorphic markers and p53 gene mutation by
      polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) were
      analyzed. RESULTS: The DNA copy number changes of seven nasal-type NK/T-cell
      lymphomas were gains on chromosomes 2q(5), 13q(4), 10q(3), 21q(2), 3q(2), 5q(2),
      and 17q(2), and losses involving chromosomes 1p(4), 17p(4), 12q(3), 13q(2), and
      6q(1). One of six cases informative for at least two markers for chromosome 6q
      showed LOH at D6S300, D6S1639, D6S261, D6S407, and D6S292. Two cases showing loss
      of 1p and 17q by CGH revealed LOH at D1S214, D1S503, and D17S559. P53 mutation
      was detected in exon 8 in one of nine cases. CONCLUSIONS: Frequent DNA losses at
      1p, 17p, and 12q and gains at 2q, 13q, and 10q suggested that these regions could
      be targets for further molecular genetic analysis to investigate tumor suppressor
      genes or oncogenes associated with tumorigenesis of NK/T-cell lymphoma.
      Infrequent alteration of 6q contrary to previous studies raises doubt about an
      implication of 6q loss in the pathogenesis of early-stage NK/T-cell lymphoma.
      Further studies on more defined cases are required to verify their association.

PMID- 11309818
TI  - Increased myeloperoxidase index and large unstained cell values can predict the
      neutropenia phase of cancer patients treated with standard dose chemotherapy.
AB  - OBJECTIVE: The objective of this study was to better understand neutropenia
      induced by standard dose chemotherapy and to verify if there are any
      hematological parameters for defining the phase and possibly the duration of
      neutropenia. METHODS: The kinetics of large unstained cells (LUCs) and
      lymphocytes was evaluated in 324 blood counts of 56 chemotherapy cycles through
      the use of a Technicon H2 or an ADVIA 120 hematology analyzer. Blood samples
      collected during the neutropenia phase were also studied by flow cytometry using
      a large panel of monoclonal antibodies. Parametric and nonparametric statistics
      were employed to compare the different variables analyzed. A linear regression
      between each variable before and after nadir and a simple linear correlation
      among the same variables in the neutropenic and recovery phase were performed.
      RESULTS: The percentage of LUCs reaches the higher value at nadir and the
      difference between the mean value of prenadir and nadir is statistically
      significant (P <.01). The number of LUCs increases during the pre and postnadir
      phase. Lymphocytes number appears stable in the prenadir phase. The MPXI index
      increases in the prenadir phase and falls at nadir and this difference is
      statistically significant(P <.01). LUCs are correlated with blasts and CD34+
      cells in the pre and postnadir phase, with CD3+/CD4+ cells in the prenadir phase,
      and with CD2+/CD56+ in the postnadir phase. CONCLUSIONS: Our data have shown that
      the estimation of both percentage of LUCs and MPXI can predict the neutropenia
      phase and orient for its duration. The lymphocyte number may be regarded as a
      parameter of risk of fever after day 5 of chemotherapy and the number of blood
      CD34+ cells may be predicted by LUC count.

PMID- 11309819
TI  - Monoclonal antibody FMC7 detects a conformational epitope on the CD20 molecule:
      evidence from phenotyping after rituxan therapy and transfectant cell analyses.
AB  - Numerous studies have reported that monoclonal antibody (mAb) FMC7 detects an
      antigen present on only a subset of circulating B lymphocytes. In particular,
      this mAb may distinguish typical B-cell chronic lymphocytic leukemia (FMC7
      negative) from other types of B-cell non-Hodgkin lymphoma (B-NHL; FMC7 positive).
      We treated patients with B-NHL with Rituxan, a chimeric CD20 mAb, and observed
      abrogation of staining not only with prototype CD20 mAb B-1 but also with mAb
      FMC7. To investigate the relation between antigens CD20 and FMC7, we performed
      mutual blocking studies that showed mutual inhibition of FMC7 and CD20. In
      addition, FMC7 modulated CD23 expression and confirmed the presence of mAb B-1 in
      B-lymphoblastoid cell lines CESS and JVM. Transient transfection of myeloid cell
      line K562 with plasmid containing CD20-encoding cDNA produced de novo expressions
      of CD20 and FMC7. Our data indicate that FMC7 binds to a particular conformation
      of the CD20 antigen, probably to a multimeric CD20 complex. We assume that FMC7
      stains positively only when CD20 antigen is present in high densities and in the
      postulated multimeric complex formation.

PMID- 11309820
TI  - Detection of MRP functional activity: calcein AM but not BCECF AM as a Multidrug
      Resistance-related Protein (MRP1) substrate.
AB  - Resistance to anticancer drugs has been attributed to an array of cellular
      changes. The multidrug resistance-related protein (MRP1) is an efflux pump whose
      overexpression confers resistance to several classes of drugs, such as the
      anthracyclines, epipodophyllotoxins, and vinca alkaloids. These drugs are
      mainstays in cancer therapy. MRP1 overexpression is hypothesized to be a
      causative agent of clinical treatment failure. Consistently accurate methods for
      detecting this protein are necessary to further understand its biology and
      delineate its possible clinical relevance. Flow cytometric analysis of multidrug
      resistance (MDR) is a valuable method to evaluate both antigen expression and
      function. Using flow cytometry, we assayed MRP1 functional activity in pediatric
      leukemic blasts and an array of MDR+ and WT cell lines. We conclude that calcein
      AM, when used in a retention assay with MRP1-specific modulators, is able to
      reliably detect MRP functional activity. 2'-7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein (BCECF AM) transport is not indicative of MRP1 overexpression.
      .

PMID- 11309821
TI  - Hemopoietic stem and precursor cell analysis in umbilical cord blood using the
      Sysmex SE-9000 IMI channel.
AB  - Circulating hematopoietic progenitor cells (HPCs) are routinely measured by flow
      cytometry using CD34 expression. As an alternative, the "immature information"
      (IMI) channel measurement of the automated hematology analyzer Sysmex SE machines
      was developed. We tested the IMI channel HPC method with umbilical cord blood
      specimens. The IMI-HPCs were compared with CD34 counts and numbers of colony
      forming units (CFUs). The IMI-HPC data were reproducible and dilution experiments
      yielded a log-linear relationship. The mean percentage of CD34(+) cells in 50
      umbilical cords was 0.43 versus 0.11 of HPCs in the IMI channel (correlation
      coefficient r = 0.67). Absolute numbers yielded 96.79 x 10(6)/L CD34(+), 33.17 x
      10(6)/L IMI-HPC, and 35.04 x 10(6)/L CFU-HPC. Receiver operating characteristics
      curves were made at various cutoff levels for CD34(+) cells to visualize
      sensitivity and specificity profiles. With median values of 13.56 x 10(6)/L for
      IMI-HPC and 20 x 10(6)/L for CD34(+) as cutoff points (the levels used in the
      laboratory to start stem cell pheresis), the percentage of false-negative
      observations was 70.4%. To exclude the influence of storage time, tests were
      repeated until 72 h after umbilical cord collection. Total white blood cell count
      decreased in most cases, whereas absolute number of IMI-HPC tended to increase in
      time. In conclusion, if HPC measurements in the IMI channel are used to monitor
      circulating stem cells during mobilization, one has to be aware of a very low
      correlation between these results and those of other methods such as CD34(+)
      analysis and colony growth. False-negative results do occur, but if events are
      seen in the IMI channel, this simple monitoring technique is useful to predict
      the presence of circulating stem cells.

PMID- 11309823
TI  - Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients
      with active ulcerative colitis: a multicenter study.
AB  - Active ulcerative colitis (UC) is characterized by activation and infiltration of
      granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated
      leukocytes can cause mucosal damage by releasing degradative proteases, reactive
      oxygen derivatives, and proinflammatory cytokines. The aim of this trial
      (conducted in 14 specialist centers) was to assess safety and efficacy of
      granulocyte and monocyte adsorption apheresis in patients with active UC most of
      whom were refractory to conventional drug therapy. We used a new adsorptive type
      extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads
      (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and
      monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each
      of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in
      combination with 24.4 +/- 3.60 mg prednisolone (mean +/- SE per patient per day,
      baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of
      monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of
      patients had remission or improved, the dose of prednisolone was reduced to 14.2
      +/- 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non
      severe side effects (in 5 patients) were reported. Based on our results, we
      believe that in patients with active severe UC, patients who are refractory to
      conventional drugs, granulocyte and monocyte adsorption apheresis is a useful
      adjunct to conventional therapy. This procedure should have the potential to
      allow tapering the dose of corticosteroids, shorten the time to remission and
      delay relapse.

PMID- 11309824
TI  - Paired comparison of apheresis platelet function after storage in two containers.
AB  - Platelet quality after storage strongly depends on the pre-storage quality as
      well as on the storage conditions determined by the storage container. In this
      paired study, we evaluated two different containers (MedSep CLX and Delmed DPL
      110). The Fresenius AS104 cell separator was used to prepare 17 platelet
      concentrates that were split and distributed into the containers to be compared.
      Cell counts, blood gas analysis, morphological scores, glucose and lactate
      levels, platelet activation, and platelet aggregation were measured before
      splitting at the day of preparation and after storage at day 3 and day 5. At day
      3, there was no significant difference between the two bags apart from increased
      lactate and decreased pCO(2) concentrations in the CLX bags. At day 5 there were
      significantly higher lactate concentrations, pO(2) levels, and aggregation after
      stimulation in the CLX group, while the glucose and pCO(2) concentrations were
      significantly lower in these platelet concentrates as compared to the DPL-110
      group. However, these parameters did not influence the functional parameters
      tested. While the platelet quality decreased during storage in all bags, the
      functional changes were nearly identical in both bags tested. We conclude that
      both bags are equivalent for 5-day storage of platelet concentrates.

PMID- 11309825
TI  - Erythrocytapheresis for Plasmodium falciparum infection complicated by cerebral
      malaria and hyperparasitemia.
AB  - In malaria due to Plasmodium falciparum, life-threatening complications are in
      part related to the degree of parasitemia. Whole blood exchange and red blood
      cell exchange (RCE) have been used for the rapid removal of parasites from the
      circulation of patients with a high parasite load complicated by cerebral,
      pulmonary, and renal dysfunction. We have treated three 5-45-year-old patients
      with hyperparasitemia and end-organ dysfunction with red cell exchange by
      automated apheresis as an adjunct to specific anti-malarial chemotherapy.
      Parasitemia dropped more than 80% in all three patients immediately after the
      exchange, and all patients had an uneventful and full recovery. In combination
      with effective anti-malarial chemotherapy, apheresis RCE is a safe and rapid
      approach to treat complicated malaria due to P. falciparum.

PMID- 11309826
TI  - Cryoprecipitate poor plasma does not improve early response in primary adult
      thrombotic thrombocytopenic purpura (TTP).
AB  - Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal disease that is
      treated with plasma exchange and typically with replacement with fresh frozen
      plasma (FFP). This approach results in an approximate 50% response rate following
      1 week of therapy and 80% survival. Cryoprecipitate poor plasma (CPP) is plasma
      from which the cryoprecipitate fraction is removed. CPP has been reported to be
      successful as salvage therapy in refractory TTP and has been suggested to be
      superior to FFP in retrospective studies. The present report compares initial
      therapy of TTP with exchange using replacement with either FFP or CPP in a multi
      institutional prospective randomized study performed by the North American TTP
      Group (NATG Group) from 1993 to 1995. Initial therapy also included
      corticosteroids. Antiplatelet drugs or vinca alkaloids were not employed. A
      severity score index, response score, and individual clinical parameters
      (platelet count, LDH x upper limit of normal, hemoglobin level, and creatinine)
      were compared at their nadir or peak values, baseline, and days +6 and +13 of
      therapy. Thirteen patients were randomized to FFP exchange and 14 to CPP
      exchange. Results were equivalent for all parameters. Survival was equal with
      three deaths in each group. These data indicate that the efficacy of FFP and CPP
      are the same in the initial treatment of TTP in adults.

PMID- 11309827
TI  - Improvement of macular function by membrane differential filtration in diabetic
      retinopathy.
AB  - BACKGROUND: Alterations of blood rheology are assumed to substantially contribute
      to the pathogenesis of diabetic retinopathy. Membrane differential filtration
      (MDF) is an extracorporeal treatment which is able to optimize rheological
      parameters by eliminating high molecular weight proteins and lipoproteins from
      the blood. The present study was designed to investigate the effects of
      repetitive MDF on visual function in diabetic retinopathy. METHODS: 11 patients
      (11 eyes) with nonproliferative or inactive proliferative diabetic retinopathy
      underwent three treatment cycles during a mean period of 18 weeks. The best
      corrected visual acuity served as the main parameter of the study. The
      measurement of visual acuity, visual field, biochemical and rheological
      parameters was carried out 24 hours pre and post each treatment cycle and at
      follow up. The mean follow up time was 9 weeks during the post treatment period.
      RESULTS: Compared to baseline examination the visual acuity improved stepwise by
      a mean value of 1.4 lines (p = 0.02) after the last treatment and remained stable
      at follow up (1.3 lines, p < 0.001). The mean defect of the visual field was
      reduced by 2.8 dB (p = 0.13) after the treatment period and by 2.5 dB (p = 0.016)
      at follow up, respectively. CONCLUSIONS: Repetitive treatment with membrane
      differential filtration is able to improve visual function in patients with
      diabetic retinopathy. The present study suggests that repetitive membrane
      differential filtration treatment could be a useful adjunct along with laser
      treatment to influence the clinical course of diabetic maculopathy.

PMID- 11309828
TI  - Presurgical plasma exchange for severe factor V deficiency.
AB  - We report two patients with severe congenital factor V deficiency, one of whom
      also had a factor V inhibitor, who required correction of their coagulopathy
      prior to surgical procedures. They underwent plasma exchange (PE) with fresh
      frozen plasma or solvent/detergent treated plasma (S/DP), with achievement of
      factor V levels satisfactory for hemostasis for their procedures. PE makes it
      possible to raise factor levels quickly and sufficiently without volume overload.
      In addition, transient reduction of inhibitor titers by PE may improve the level
      of correction achievable during the perioperative period. The advent of S/DP
      promises to provide an added increment of safety in patients exposed to
      significant volumes of plasma during PE.

PMID- 11309829
TI  - Leukodepletion for acute lymphocytic leukemia in a three-week-old infant.
AB  - We report the smallest infant (4.5 kg) to receive leukapheresis as an immediate
      treatment for Infantile Acute Lymphocytic Leukemia. Leukodepletion helps prevent
      the risks of hyperviscosity and cerebrovascular and pulmonary leukostasis. In
      addition, it is a desirable precursor to chemotherapy to potentially reduce
      metabolic and renal complications associated with rapid cell lysis. Because of
      this infant's small size, she presented us with multiple concerns, including
      hypocalcemia from citrate anticoagulation, extracorporeal volume and fluid
      balance, inlet flow rates. and establishment of adequate interface. Our positive
      experience in performing this procedure suggests that cytapheresis is a feasible
      treatment even for very young infants.

PMID- 11309830
TI  - Efficiency of the cell separator AMICUS for platelet depletion in the treatment
      of essential thrombocythemia.

PMID- 11309831
TI  - Immunovirological improvement in partially HAART responder HIV-infected patients
      by monocyte adsorption apheresis.

PMID- 11309832
TI  - Lepromatous vasculitis successfully treated by plasma exchange (PE).
AB  - Vascular involvement is presently considered a "common pathway" in a number of
      diseases that is mediated by circulating immune complexes (CIC). CIC are found in
      the circulation when the disease is active and in single patients their level may
      parallel disease activity. Lepromatous leprosis is characterized by the presence
      of CIC and deposits of immunoglobulins and complement in vascular lesions of the
      different organs and an Arthus-like mechanism is considered as the basis for the
      clinical picture. The same mechanism is considered to play an essential
      pathophysiologic role in Lucio's phenomenon, which is characterized by
      lymphohistiocytic vascular infiltrates with or without thrombosis and secondary
      cutaneous infarction. Lepromatous vascular involvement is mediated by CIC whose
      antigen composition is known, the same as it is with HCV mediated
      cryoglobulinemia, HBV positive panarteritis nodosa, rheumatoid vasculitis, or
      Wagner's granulomatosis, which are usually treated by PE [1-3]. PE has been
      employed for lepromatous vasculitis since 1979 [4] and other cases have been
      successfully treated afterwards [5,6]. We report on another patient successfully
      treated by plasma exchange.

PMID- 11309833
TI  - Plasma exchange for severe attacks of inflammatory demyelinating diseases of the
      central nervous system.
AB  - Plasma exchange has not been widely accepted as a treatment for multiple
      sclerosis. However, several uncontrolled studies have suggested that patients
      with severe attacks of MS and other inflammatory demyelinating disease may
      improve rapidly after plasma exchange treatment. We recently completed a
      randomized, sham-controlled, crossover clinical trial of plasma exchange in 22
      patients with idiopathic inflammatory demyelinating diseases of the central
      nervous system. Twelve had MS and ten had other inflammatory demyelinating
      disease syndromes. Forty-two percent of patients experienced moderate or greater
      recovery over 2 weeks of active treatment administered every other day while only
      6% of patients experienced similar improvement while receiving sham treatment.
      Three patients who failed the sham treatment subsequently improved rapidly after
      crossover to active treatment; no patient who failed active treatment improved
      after crossover to sham. This study illustrates the importance of designing
      randomized clinical trials based on the treatment regimen and patient population
      studied in the uncontrolled reports that suggested treatment efficacy. Plasma
      exchange should be considered for patients with idiopathic inflammatory
      demyelinating disease syndromes when they have failed corticosteroid therapy.

PMID- 11309834
TI  - Platelet transfusion therapy.
AB  - The relative merits of apheresis platelets and platelet concentrates are
      undergoing debate due to evolving issues of safety, inventory, and cost. The
      application of photochemical inactivation technology may eliminate any rationale
      for the use of apheresis platelets rather than pooled platelet concentrates, so
      that the relative merits of these two alternatives will be debated over costs and
      inventory. Doses of apheresis platelets are determined by donor platelet count
      and by platelet yield. The generation of a platelet apheresis inventory has been
      accompanied by a decline in whole blood inventory; research into the impact of
      these distinct donor pools on national blood policy is needed.

PMID- 11309835
TI  - Extracorporeal immunoadsorption with protein A: technical aspects and clinical
      results.

PMID- 11309836
TI  - Centrosome and spindle pole microtubules are main targets of a fluorescent taxoid
      inducing cell death.
AB  - Microtubules offer a very large local concentration of binding sites for
      cytotoxic taxoids or for hypothetical endogenous regulators. Several compounds
      from diverse sources stabilize microtubules and arrest cell division similarly to
      the antitumour drug Taxol. We have investigated the subcellular location of the
      Taxol binding sites, employing a fluorescent taxoid (FLUTAX) that reversibly
      interacts with the Taxol binding sites of microtubules and induces cellular
      effects similar to Taxol. The specific binding of FLUTAX to a fraction of the
      available cellular binding sites effectively inhibits division of cultured human
      tumour cells at G(2)/M, and triggers apoptotic death. The loci of reversible
      binding, directly imaged in intact U937 cells treated with cytotoxic doses of
      fluorescent taxoid are the centrosomes, with a few associated microtubules in
      interphase cells, and the spindle pole microtubules in mitotic cells, instead of
      uniformly labelling the microtubule cytoskeleton. Cytoskeletal lesions induced
      and visualized with FLUTAX consist of microtubule bundles and abnormal mitoses,
      including monopolar spindles and highly fluorescent multipolar spindles. The
      multiple asters and monopolar spindles mark arrested U937 leukaemia and OVCAR-3
      ovarian carcinoma cells on their path to apoptosis (as well as K562, HeLa, and
      MCF-7 cells). Depending on the FLUTAX treatment, OVCAR-3 cells died from abnormal
      mitosis or from a subsequent interphase with double chromatin content and
      lobulated nuclei (micronuclei), indicating impairment of centrosome separation.
      Fragmented centrosomes could be observed in FLUTAX-treated non-transformed
      3T3.A31 cells, which developed micronuclei but were resistant to apoptosis. These
      results strongly suggest that centrosomal impairment by taxoid binding during
      interphase, in addition to the suppression of the kinetochore microtubule
      dynamics in the mitotic spindle, is a primary cause of cell cycle de-regulation
      and cell death.

PMID- 11309838
TI  - Measurement of the force and torque produced in the calcium response of
      reactivated rat sperm flagella.
AB  - Rat sperm that are demembranated with Triton X-100 and reactivated with Mg-ATP
      show a strong mechanical response to the presence of free calcium ion. At pCa <
      4, the midpiece region of the flagellum develops a strong and sustained curvature
      that gives the cell the overall appearance of a fishhook [Lindemann and Goltz,
      1988: Cell Motil. Cytoskeleton 10:420-431]. In the present study, the force and
      torque that maintain the calcium-induced hook have been examined quantitatively.
      In addition, full-length and shortened flagella were manipulated to evaluate the
      plasticity of the hooks and determined the critical length necessary for
      maintaining the curvature. The hooks were found to be highly resilient, returning
      to their original configuration (>95%) after being straightened and released. The
      results from manipulating the shortened flagella suggest that the force holding
      the hook in the curved configuration is generated in the basal 60 microm of the
      flagellum. The force required to straighten the calcium-induced hooks was
      measured with force-calibrated glass microprobes, and the bending torque was
      calculated from the measured force. The force and torque required to straighten
      the flagellum were found to be proportional to the change in curvature of the
      hooked region of the flagellum, suggesting an elastic-like behavior. The average
      torque to open the hooks to a straight position was 2.6 (+/-1.4) x 10(-7) dyne x
      cm (2.6 x 10(-14) N x m) and the apparent stiffness was 4.3 (+/-1.3) x 10(-10)
      dyne x cm(2) (4.3 x 10(-19) N x m(2)). The stiffness of the hook was determined
      to be approximately one quarter the rigor stiffness of a rat sperm flagellum
      measured under comparable conditions.

PMID- 11309837
TI  - Differential expression and localization of neuronal intermediate filament
      proteins within newly developing neurites in dissociated cultures of Xenopus
      laevis embryonic spinal cord.
AB  - The molecular subunit composition of neurofilaments (NFs) progressively changes
      during axon development. In developing Xenopus laevis spinal cord, peripherin
      emerges at the earliest stages of neurite outgrowth. NF-M and XNIF (an alpha
      internexin-like protein) appear later, as axons continue to elongate, and NF-L is
      expressed after axons contact muscle. Because NFs are the most abundant component
      of the vertebrate axonal cytoskeleton, we must understand why these changes occur
      before we can fully comprehend how the cytoskeleton regulates axon growth and
      morphology. Knowing where these proteins are localized within developing neurites
      and how their expression changes with cell contact is essential for this
      understanding. Thus, we examined by immunofluorescence the expression and
      localization of these NF subunits within dissociated cultures of newly
      differentiating spinal cord neurons. In young neurites, peripherin was most
      abundant in distal neuritic segments, especially near branch points and extending
      into the central domain of the growth cone. In contrast, XNIF and NF-M were
      usually either absent from very young neurites or exhibited a proximal to distal
      gradient of decreasing intensity. In older neurites, XNIF and NF-M expression
      increased, whereas that of peripherin declined. All three of these proteins
      became more evenly distributed along the neurites, with some branches staining
      more intensely than others. At 24 h, NF-L appeared, and in 48-h cultures, its
      expression, along with that of NF-M, was greater in neurites contacting muscle
      cells, arguing that the upregulation of these two subunits is dependent on
      contact with target cells. Moreover, this contact had no effect on XNIF or
      peripherin expression. Our findings are consistent with a model in which
      peripherin plays an important structural role in growth cones, XNIF and NF-M help
      consolidate the intermediate filament cytoskeleton beginning in the proximal
      neurite, and increased levels of NF-L and NF-M help further solidify the
      cytoskeleton of axons that successfully reach their targets.

PMID- 11309839
TI  - Thermal activation of single kinesin molecules with temperature pulse microscopy.
AB  - Conventional kinesin is a processive motor protein that keeps "walking" along a
      microtubule using chemical energy released by ATP hydrolysis. We previously
      studied the effects of temperature between 15 degrees and 35 degrees C on the
      moving velocity, force, and processivity of single kinesin molecules using a bead
      assay [Kawaguchi and Ishiwata, 2000b: Biochem Biophys Res Commun 272:895-899].
      However, we could not examine the effects of temperature higher than 35 degrees C
      because of the thermal damage to proteins. Here, using temperature pulse
      microscopy (TPM) [Kato et al., 1999: Proc Natl Acad Sci USA 96:9602-9606], we
      could examine the temperature dependence of the gliding velocity of single
      kinesin molecules interacting with a microtubule above 35 degrees C up to 50
      degrees C (instantaneously, approximately 60 degrees C), where the velocity
      reached 3.68 microm/s, the highest ever reported. The Arrhenius plot showed no
      breaks between 15 degrees and 50 degrees C with a unique activation energy of
      about 50 kJ/mol, suggesting that the molecular mechanism of kinesin motility is
      common over a broad temperature range including physiological temperature.

PMID- 11309840
TI  - Electron microscopic immunocytochemical detection of PSD-95, PSD-93, SAP-102, and
      SAP-97 at postsynaptic, presynaptic, and nonsynaptic sites of adult and neonatal
      rat visual cortex.
AB  - Membrane-associated guanylate kinases (MAGUKs) assemble protein complexes at
      sites of cell-cell contact. At excitatory synapses in brain, MAGUKs localize to
      the postsynaptic density (PSD) and interact with N-methyl-D-aspartate (NMDA)
      glutamate receptors and downstream signaling proteins. However, NMDA receptors
      are not restricted to the PSDs, as electron microscopic immunocytochemical (EM
      ICC) results indicate that NMDA receptors also occur at nonsynaptic portions of
      dendrites, perhaps functioning as reserves for rapid insertion into synaptic
      membranes in response to appropriate synaptic activity. NMDA receptors also occur
      in axons, at least in part to support glutamate-dependent enhancement of
      transmitter release. In this study, a systematic EM-ICC survey was performed to
      determine whether the distributions of four neuronal MAGUKs-PSD-95, PSD-93, SAP
      102, and SAP-97-resemble that of NMDA receptors. Quantitative analysis revealed
      that the density of PSD-95 over thick PSDs of asymmetric axo-spinous synaptic
      junctions is 2-3-fold the level in the immediately adjacent cytoplasm of spines
      and terminals, while symmetric synapses show no association with PSD-95.
      Similarly, all four MAGUKs occur over PSDs of spines. However, we also detected
      MAGUK immunoreactivity, albeit more diffusely, along presynaptic membranes and in
      the cytoplasm of axons and dendritic shafts. In fact, the overall distribution of
      PSD-95 within the neuropil is equally prevalent along plasma membranes (including
      synaptic portions) as in the cytoplasm, away from plasma membranes. These results
      suggest that MAGUKs have dual roles: to maintain receptors at synapses and to
      regulate shuttling of receptors between nonsynaptic and synaptic sites.

PMID- 11309841
TI  - Distribution of members of the PSD-95 family of MAGUK proteins at the synaptic
      region of inner and outer hair cells of the guinea pig cochlea.
AB  - PDZ-domain containing proteins of the MAGUK (membrane-associated guanylate
      kinase) family target, anchor, and cluster receptors and channels to subcellular
      sites. Among the MAGUK proteins, the members of the PSD-95 family (MAGUKs: PSD
      95, PSD-93, SAP-97, and SAP-102) target and anchor glutamate receptors to the
      synaptic terminals. Associations of glutamate receptors with MAGUKs have been
      described in the brain but not in the cochlea. In this study, RT-PCR,
      immunofluorescence microscopy, and immunoelectron microscopy were used to
      investigate the presence and distribution of MAGUK proteins in the organ of
      Corti. The presence of the mRNA for PSD-95, PSD-93, SAP-97, and SAP-102 in the
      organ of Corti was confirmed by RT-PCR. Immunocytochemistry using a "pan-MAGUK"
      antibody, which recognizes all four MAGUK proteins, and selective antibodies
      against these proteins revealed that all four MAGUKs are present within the base
      of inner hair cells while all except SAP-97 are found within the base of the
      outer hair cells. In addition, PSD-93 and PSD-95 are found in postsynaptic
      afferent terminals on inner hair cells, while postsynaptic afferent terminals on
      outer hair cells have PSD-93.

PMID- 11309842
TI  - Opioid peptide receptor studies. 15. Relative efficacy of 4-[(N-allyl-3-methyl-4
      piperidinyl)phenylamino]-N,N-diethylbenzamide and related compounds at the cloned
      human delta-opioid receptor.
AB  - Previous data obtained from both binding and functional assays demonstrated that
      (-)-4-[(N-allyl-3-methyl-4-piperidinyl)phenylamino]-N,N-diethylbenzamide [(-)
      RTI5989-54] displays selective binding and full agonist activity relative to (+/
      )-RTI5989-54 for the delta opioid receptor. The present study was conducted to
      evaluate the activities of structurally diverse opioid receptor delta ligands in
      the [(35)S]GTP-gamma-S binding assay, comparing the relationship between receptor
      binding, activation, efficacy, and intrinsic efficacy. The data, obtained with
      cloned human delta receptors, demonstrated that (-)-RTI5989-54 behaves like the
      highly selective delta agonist SNC80. Addition of the hydroxyl group to RTI5989
      54 (RTI5989-61) or replacement of the allyl group with the trans-crotyl group on
      the piperidine nitrogen of RTI-5989-61 (RTI5989-62) increased binding affinity,
      produced full agonist activity, and decreased intrinsic efficacy at the delta
      opioid receptor. The order of potency for the EC(50) (GTP-gamma-S) was RTI5989-62
      (0.20 nM) > RTI5989-61 (0.43 nM) > SNC80 (1.92 nM) > DPDPE (3.50 nM) > (-)
      RTI5989-54 (17.6 nM) > (+/-)-RTI5989-54 (65.6 nM) > (+)-RTI5989-54 (483 nM).
      RTI5989-61 and RTI5989-62 were fully efficacious, but had intrinsic efficacy
      values that were 2.2-3.1 times lower than that of DPDPE and SNC80. Comparison of
      the binding K(i) in competitively inhibiting [(125)I]IOXY binding to the
      functional K(i) for delta antagonists [Ki (IOXY)/Ki (GTP-gamma-S)] shows that
      antagonists might antagonize agonist-evoked neurochemical effects with equal
      magnitude while occupying different proportions of target receptors.

PMID- 11309843
TI  - Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide
      significantly alters the activity of ventral tegmental area dopamine neurons: an
      electrophysiological study.
AB  - In this study, we determined the activity of midbrain dopamine (DA) neurons in
      male albino rats following the intracerebroventricular (i.c.v.) administration of
      antisense oligodeoxynucleotide (aODN) against the mRNA for the NR1 subunit of the
      NMDA receptor. In addition, the effect of aODN on the specific binding of the
      NMDA receptor ligand [(3)H]MK-801 was also examined in various brain areas,
      including the midbrain. Antisense ODN against the NR1 mRNA, the corresponding
      sense ODN (sODN) or saline was continuously administered into the right ventricle
      of rats by osmotic minipumps for 7 days (20 nmol/day). Autoradiographic binding
      studies indicated that aODN significantly reduced the density of [(3)H]MK-801
      binding by an average of 20-30% in several forebrain regions, including the
      anterior cingulate cortex, caudate putamen, and nucleus accumbens. However,
      [(3)H]MK-801 binding was not significantly altered in the ventral tegmental area
      (VTA) or substantia nigra pars compacta (SNC). Subsequently, using the technique
      of extracellular single-unit recording, the number, as well as the firing
      pattern, of spontaneously active DA neurons was determined in the VTA and SNC.
      The administration of aODN did not significantly alter the number of
      spontaneously active VTA and SNC DA neurons compared to saline- of sODN-treated
      animals. Furthermore, the firing pattern of spontaneously active SNC DA neurons
      was not significantly altered. However, for spontaneously active VTA DA neurons,
      the administration of aODN significantly decreased the percent events in bursts,
      number of bursts, and percentage of DA neurons exhibiting a bursting pattern
      compared to saline- and sODN-treated animals, i.e., neurons show less bursting
      activity. The present results suggest that subchronic aODN treatment against the
      mRNA for the NR1 subunit of the NMDA receptors can reduce NMDA receptor number
      and can result in an altered activity of spontaneously active VTA DA neurons in
      anesthetized rats.

PMID- 11309844
TI  - Inhibition of morphine withdrawal by the NMDA receptor antagonist MK-801 in rat
      is age-dependent.
AB  - This study investigated the effects of the NMDA receptor antagonist MK-801 on the
      development of morphine dependence in 7-, 14-, and 21-day-old rat pups. For 6.5
      days, starting at 1, 8, or 15 days of age, rats were pretreated with MK-801 (0.03
      or 0.1 mg/kg, bid) or saline; 15 min later, morphine sulfate (10 mg/kg) or saline
      was injected to induce opiate dependence. On the afternoon of the seventh day,
      pups were injected with MK-801 (0.1 mg/kg) or saline and 15 min later with
      naltrexone (1 mg/kg) to precipitate withdrawal. Pups were then placed in a warm
      chamber with the litter and their behavior scan-sampled every 15 sec for a total
      of 15 min. MK-801 failed to inhibit morphine withdrawal in the 7-day-old rat, but
      did attenuate the development of morphine dependence in both the 14- and 21-day
      old rats. These results suggest that the NMDA receptor is not functionally active
      in opiate withdrawal until around the second to third week of postnatal life in
      the rat and that there exists a transition period for the NMDA receptor to play a
      role in the development of opiate dependence and withdrawal.

PMID- 11309845
TI  - Inhibition of cytochrome P450 2E1 induces an increase in extracellular dopamine
      in rat substantia nigra: a new metabolic pathway?
AB  - We presented data previously on dopamine (DA) synthesis and catabolism in the rat
      substantia nigra (SN) suggesting that a substantial part of the synthesized DA in
      this brain part is metabolized by unknown nonclassical metabolic pathways. On the
      basis of that a relatively high density of cytochrome P450 2E1 (CYP 2E1) has been
      detected in rat SN the aim of the present study was to investigate the
      possibility that this enzyme is involved in the metabolism of DA. Systemic
      administration of either phenylethyl isothiocyanate (100 mg/kg ip),
      diethyldithiocarbamate (500 mg/kg, ip) or diallyl sulfide (200 mg/kg, sc or ip),
      three different inhibitors of cytochrome P450 2E1, induced an increase of the
      extracellular DA concentration in the SN, measured with microdialysis in awake
      rats, by 130%, 90%, and 35%, respectively. A tendency to increased concentrations
      of the classical DA metabolites in the dialysate from the SN was also observed in
      some experiments. In the striatum, no profound effects were induced by the drugs
      on the concentrations of DA or its metabolites. The results show that CYP 2E1
      activity affects dopaminergic neurotransmission in the SN, possibly by
      participating in DA metabolism. Other mechanisms, such as the influence on the DA
      transporter or the release process cannot, however, be ruled out.

PMID- 11309846
TI  - Activation of calpain may alter the postsynaptic density structure and modulate
      anchoring of NMDA receptors.
AB  - Elevation of calcium during sustained synaptic activity may lead to the
      activation of the postsynaptic calcium-dependent protease calpain and thus could
      alter the integrity and localization of endogenous proteins. The distribution of
      anchoring proteins for neuroreceptors is an important determinant of the efficacy
      of neuronal transmission. Many of these anchoring proteins are concentrated
      within the postsynaptic density (PSD). In the present study, we examined the
      effects of calpain II on isolated PSDs using biochemical and electron microscopic
      techniques. Biochemical analysis reveals that PSD-95, a clustering molecule which
      anchors NMDA receptors by interaction with their NR2 subunits, as well as the NR2
      subunits themselves, are cleaved by calpain. On the other hand, under conditions
      where all the PSD-95 protein is cleaved, actin and alpha-actinin-a protein
      thought to anchor NMDA receptors to actin filaments-remain intact. For analysis
      by electron microscopy, PSDs were adsorbed on glass, immunogold-labeled with an
      antibody to PSD-95, slam frozen, freeze dried, and rotary shadowed. Electron
      micrographs of replicas indicate that PSDs are disc-shaped and are composed of a
      lattice-like structure which labels with PSD-95 immunogold. After calpain
      treatment, PSDs adsorbed on glass become thinner overall and the lattice becomes
      fragmented. Altogether, these results suggest that calpain activity could produce
      changes in the organization of the PSD and, by cleaving PSD-95 associated with
      the PSD lattice, could modify the anchoring of NMDA receptors.

PMID- 11309847
TI  - The 14th annual International Mammalian Genome Society Conference: a glimpse into
      the future of murine functional genomics.

PMID- 11309848
TI  - Concurrent expression of recombination activating genes 1 and 2 in zebrafish
      olfactory sensory neurons.
AB  - Each olfactory sensory neuron (OSN) expresses a single odorant receptor (OR) from
      a large repertoire of clustered OR genes. It has been hypothesized that OR gene
      regulation may involve stochastic DNA rearrangement, which in lymphocytes
      requires the recombination activating genes, rag1 and rag2. We have recently
      demonstrated that rag1 is expressed in zebrafish OSNs. Here we report that rag2,
      the obligate partner for rag1 function, is also expressed in OSNs and that its
      expression pattern mimics that of rag1. The onset of rag1 and rag2 expression
      preceded that of known zebrafish ORs and the number of rag1-positive OSNs
      corresponded with the number expressing the olfactory cyclic nucleotide-gated
      cation channel, an OSN marker. Zebrafish OSNs are the first example of concurrent
      rag expression in a nonlymphoid tissue. The expression of rag1 and rag2 in OSNs
      adds to the list of similarities between the olfactory and immune systems that
      includes monoallelic and mutually exclusive gene expression.

PMID- 11309849
TI  - The winged helix/forkhead transcription factor Foxq1 regulates differentiation of
      hair in satin mice.
AB  - Satin (sa) homozygous mice have a silky coat with high sheen arising from
      structurally abnormal medulla cells and defects in differentiation of the hair
      shaft. We demonstrate that the winged helix/forkhead transcription factor, Foxq1
      (Forkhead box, subclass q, member 1) is mutant in sa mice. An intragenic deletion
      was identified in the radiation-induced satin mutant of the SB/Le inbred strain;
      a second allele, identified by an N-ethyl-N-nitrosourea (ENU) mutagenesis screen,
      has a missense mutation in the conserved winged helix DNA-binding domain.
      Homozygous mutants of the two alleles are indistinguishable. We show that Foxq1
      is expressed during embryogenesis and exhibits a tissue-restricted expression
      pattern in adult tissues. The hair defects appear to be restricted to the inner
      structures of the hair; consequently, Foxq1 has a unique and distinct function
      involved in differentiation and development of the hair shaft. Despite an
      otherwise healthy appearance, satin mice have been reported to exhibit suppressed
      NK-cell function and alloimmune cytotoxic T-cell function. We show instead that
      the immune defects are attributable to genetic background differences.

PMID- 11309850
TI  - Characterization of Amphioxus AmphiVent, an evolutionarily conserved marker for
      chordate ventral mesoderm.
AB  - Structure and developmental expression are described for amphioxus AmphiVent, a
      homolog of vertebrate Vent genes. In amphioxus, AmphiVent-expressing ventral
      mesoderm arises at midneurula by outgrowth from the paraxial mesoderm, but in
      vertebrates, Vent-expressing ventral mesoderm originates earlier, at the gastrula
      stage. In other embryonic tissues (nascent paraxial mesoderm, neural plate,
      endoderm, and tailbud), AmphiVent and its vertebrate homologs are expressed in
      similar spatiotemporal domains, indicating conservation of many Vent gene
      functions during chordate evolution. The ventral mesoderm evidently develops
      precociously in vertebrates because their relatively large embryos probably
      require an early and extensive deployment of the mesoderm-derived circulatory
      system. The vertebrate ventral mesoderm, in spite of its strikingly early advent,
      still resembles the nascent ventral mesoderm of amphioxus in expressing Vent
      homologs. This coincidence may indicate that Vent homologs in vertebrates and
      amphioxus play comparable roles in ventral mesoderm specification.

PMID- 11309851
TI  - Increased transgene expression by the mouse tyrosinase enhancer is restricted to
      neural crest-derived pigment cells.
AB  - In this study, we have addressed the impact of the mouse tyrosinase enhancer on
      regulated expression from the mouse tyrosinase promoter during embryonic
      development. Stable and transient transgenic experiments using the reporter gene
      lacZ reveal that (1) expression is detected in neural crest-derived melanoblasts
      from E11.5 onward, (2) the enhancer does not increase transgenic expression in
      optic cup-derived pigment cells of the retinal pigment epithelium (RPE), and (3)
      expression in the telencephalon is not any longer detected. The importance of the
      enhancer for expression in pigment cells of the eye was further investigated in
      adult mice using an attenuated diphtheria toxin A gene. This demonstrated that in
      presence of the enhancer the transgene expression is specifically targeted to
      neural crest-derived melanocytes of the choroid and not, or slightly, to the RPE.
      This suggests that tyrosinase is differentially regulated in the two pigment cell
      lineages, and that this promoter can be used to target expression preferentially
      to the neural crest-derived melanocyte lineage.

PMID- 11309852
TI  - Cell populations and morphogenetic movements underlying formation of the avian
      primitive streak and organizer.
AB  - The cell populations and morphogenetic movements that contribute to the formation
      of the avian primitive streak and organizer-Hensen's node-are poorly understood.
      We labeled selected groups of cells with fluorescent dyes and then followed them
      over time during formation and progression of the primitive streak and formation
      of Hensen's node. We show that (1) the primitive streak arises from a localized
      population of epiblast cells spanning the caudal midline of Koller's sickle, with
      the mid-dorsal cells of the primitive streak arising from the midline of the
      epiblast overlying Koller's sickle and the deeper and more lateral primitive
      streak cells arising more laterally within the epiblast overlying the sickle,
      from an arch subtending about 30 degrees; (2) convergent extension movements of
      cells in the epiblast overlying Koller's sickle contribute to formation of the
      initial primitive streak; and (3) Hensen's node is derived from a mixture of
      cells originating both from the epiblast just rostral to the incipient (stage 2)
      primitive streak and later from the epiblast just rostral to the elongating
      (stage 3a/b) primitive streak, as well as from the rostral tip of the progressing
      streak itself. Collectively, these results provide new information on the
      formation of the avian primitive streak and organizer, increasing our
      understanding of these important events of early development of amniotes.

PMID- 11309853
TI  - The arrest gene is required for germline cyst formation during Drosophila
      oogenesis.
AB  - In Drosophila, oogenesis is initiated when a germline stem cell produces a
      differentiating daughter cell called the cystoblast. The cystoblast undergoes
      four rounds of synchronous divisions with incomplete cytokinesis to generate a
      syncytial cyst of 16 interconnected cystocytes, in which one cystocyte
      differentiates into an oocyte. Strong mutations of the arrest (aret) gene disrupt
      cyst formation and cause the production of clusters of ill-differentiated
      germline cells that retain cellular and molecular characteristics of cystoblasts.
      These mutant germ cells express high levels of BAM-C and SXL proteins in the
      cytoplasm but do not accumulate markers for advanced cystocytes or
      differentiating oocytes, such as the nuclear localization of SXL or the
      accumulation of osk mRNA, orb mRNA, and cytoplasmic dynein. However, the mutant
      germ cells do not contain spectrosomes, the cytoplasmic structure that
      objectifies the divisional asymmetry of the cystoblast. The aret mutant germ
      cells undergo active mitosis with complete cytokinesis. Their mitosis is
      accompanied by massive necrosis, so that the number of germ cells in a stem cell
      derived cluster ranges from one to greater than 70. These defects of aret mutants
      reveal a novel function of aret as the first gene with a defined function in the
      cystoblast to cyst transition during early oogenesis.

PMID- 11309854
TI  - [Refusal of treatment, emotions of nurses: clinical cases].

PMID- 11309855
TI  - [Euthanasia, ethics and exception].

PMID- 11309857
TI  - [Dietary oils and fatty substances].

PMID- 11309856
TI  - [Epileptic crises in old age].

PMID- 11309858
TI  - [Psychomotor disorders and geriatrics].

PMID- 11309860
TI  - [The coordinating function of nurses].

PMID- 11309859
TI  - [Abuse of the aged].

PMID- 11309861
TI  - [Marital regimes].

PMID- 11309862
TI  - [Unreasonable therapeutic obstinacy].

PMID- 11309864
TI  - [National rules on Alzheimer disease].

PMID- 11309863
TI  - [Therapeutic mediations in psycho-geriatric hospitals].

PMID- 11309865
TI  - [Therapeutic obstinacy, place of scientific basis in decision making in nursing].

PMID- 11309866
TI  - Current issues in nutrition and child oral health.

PMID- 11309867
TI  - Variations in number and morphology of permanent teeth in 7-year-old Swedish
      children.
AB  - OBJECTIVES: To establish the prevalence of numerical and morphological variations
      of permanent teeth in Swedish 7-year-olds and to accept or reject the hypothesis
      of a higher prevalence for these conditions in northern Sweden compared to other
      areas. DESIGN: Cross-sectional. SETTING: Department of Odontology/Pedodontics,
      Umea University, Sweden. SAMPLE AND METHODS: A total of 739 healthy Caucasian 7
      year-olds residing in the city of Umea, northern Sweden in 1976. The children
      were examined clinically and radiographically. RESULTS: The prevalence of
      hypodontia (excluding third molars) in girls was 8.4%, in boys 6.5%, and in both
      sexes combined 7.4%. Of the children with hypodontia, the majority (90.9%) lacked
      one or two teeth. Lower second premolars were the teeth most frequently missing.
      The prevalence of hyperdontia was 1.9%; 11 girls and three boys were affected;
      78% of the supernumerary teeth were mesiodenses. Of the morphological variations,
      peg-shaped upper lateral incisors were found in 0.8% of the children, double
      formation (gemination) in 0.3%, taurodontism in 0.3% and dens invaginatus in
      6.8%. One diagnosis was found in 18% of the children, and in almost 8% of them
      more than one diagnosis was found. CONCLUSIONS: The results agree with those
      obtained in similar populations and are considered representative of this ethnic
      group. The hypothesis of a genetically determined higher prevalence of numerical
      and morphological variations in the study population was not verified.

PMID- 11309868
TI  - Betel quid chewing among Bangladeshi adolescents living in east London.
AB  - OBJECTIVES: Ascertain level and predictors of betel quid (pan) chewing in
      Bangladeshi adolescents. DESIGN: Cross sectional questionnaire study. SETTING:
      Bangladeshi cultural centres in East London. SAMPLE: Consecutive adolescents
      attending 4 randomly selected centres. METHOD: Self-completed questionnaire.
      RESULTS: 204 (70%) of 290 teenagers invited to participate did so. Fifty-eight
      (28%) chewed pan; 30 (51%) of whom chewed on most days. The median age of first
      chewing was 9 years. Only 7 (2%) added tobacco to their quids. Pan chewers tended
      to come from lower socio-economic status families, liked the taste of pan and
      were less inclined to think that it adversely affected their appearance or that
      it could cause cancer. CONCLUSIONS: The prevalence of pan chewing was lower than
      that found among adults reported in earlier studies in the UK. This reduction in
      the level of pan chewing could be attributed to acculturation. Few teenagers knew
      about the association between pan chewing and cancer but the widespread concern
      about the effect of pan chewing on the appearance of their mouth suggests this is
      a useful health promotion message within common risk/health factor approach.

PMID- 11309869
TI  - Comprehensive dental care for children with rampant caries under general
      anaesthesia.
AB  - OBJECTIVE: Critical reflection on treatment strategy for dental rehabilitation of
      young children with rampant caries using day-stay general anaesthesia at a
      university dental clinic. DESIGN: Cross-sectional analysis of 98 cases. SETTING:
      The study was undertaken at the university paediatric dental clinic of Leuven,
      Belgium. SAMPLE AND METHODS: The sample consisted of 98 healthy patients referred
      for dental treatment under general anaesthesia with a mean age of 4.8 (+/- 1.1)
      years and mean dmft-score of 9.3 (+/- 3.0). Data were obtained by history taking,
      clinical examination, questionnaires (filled in by parents) and standardized data
      records (filled in by dentists and nurses in the recovery area and day-stay
      clinic). RESULTS: Most patients were referred by their private dentist (74.5%)
      because of a need for extensive dental treatment in an uncooperative child.
      Induction of anaesthesia was upsetting in a significant number of cases (68% of
      children). The mean duration of the whole procedure was 80.9 (+/- 24.7) minutes.
      A mean number of 7.2 (+/- 2.9) primary teeth were filled and 1.8 (+/- 2.0)
      extracted per patient. Post-operative problems (nausea/vomiting, temperature
      rise) were seen in only 8.2% of the patients. CONCLUSIONS: The technique used at
      this centre allows for extensive dental treatment of young children with a high
      level of acceptability and minimal morbidity, using day-stay general anaesthesia.
      Based on this review, it became clear that less upsetting methods for the
      induction of anaesthesia need to be explored. Criteria for the administration of
      antibiotics need to be defined more clearly and the use of stainless steel crowns
      should be envisaged for restorations on primary molars. The global outcome of
      this treatment provision in children at high caries risk should be evaluated over
      a longer period, including an evaluation of oral health status, restorative
      treatment (conservation vs. extraction) and behavioural aspects.

PMID- 11309870
TI  - Provision of Atraumatic Restorative Treatment (ART) restorations to Chinese pre
      school children--a 30-month evaluation.
AB  - OBJECTIVES: The objectives of this study were: to provide restorations using the
      ART approach to pre-school children in Southern China in a kindergarten
      environment, using a high-strength glass-ionomer restorative material; to assess
      the acceptability of this approach and to evaluate on a longitudinal basis the
      restorations placed. SAMPLE AND METHODS: A total of 170 ART restorations were
      placed in 95 children, aged 5.1 +/- 0.7 years, by seven final-year dental
      students using standard ART procedures and hand instruments. The restorations
      were evaluated every six months thereafter by two calibrated independent
      examiners using explorers and mouth-mirrors. RESULTS: 93% of the children
      reported that they did not feel pain during treatment and 86% were willing to
      receive ART restorations again. The cumulative 12- and 30-month survival rates of
      Class I restorations were 91% and 79%, respectively. The corresponding figures
      for Class V restorations were 79% and 70%, while those for Class II restorations
      were 75% and 51%. The failure rates of Class III and IV restorations were high
      with more than half of them scored as missing within the first year. CONCLUSIONS:
      The ART approach was shown to be acceptable to Chinese pre-school children for
      providing restorative dental care outside the traditional clinical setting. The
      success rates were high for Class I and V restorations in primary teeth, modest
      for Class II, and low for Class III and IV restorations.

PMID- 11309871
TI  - Intra-nasal midazolam in conscious sedation of young paediatric dental patients.
AB  - OBJECTIVES: To compare the effects of 3 different doses of intra-nasal midazolam
      in the conscious sedation of young paediatric dental patients and to compare the
      effectiveness of the sedation in the fasting and non-fasting child. DESIGN:
      Double blind random controlled trial. SAMPLE AND METHODS: Thirty-eight
      uncooperative young children aged 2-5 years (mean age 4.02 years) were randomly
      assigned to one of 3 groups. The groups and the doses of midazolam administered
      intra-nasally were A: 0.3 mg/kg, B: 0.4 mg/kg, and C: 0.5 mg/kg body weight. Each
      child in each group had two visits for restorative treatment: one without food
      (fasting) and the other with soft drink and light food (non-fasting) before
      treatment. Child behaviour and sedative effects were evaluated using the scoring
      system of Houpt. The vital signs were monitored continuously using a pulse
      oximeter and Dinamap machine. RESULTS: There was rapid onset of sedation with the
      maximal effect between 8 and 15 minutes. This sedation lasted for 25-40 minutes
      in Groups A and B and for 60 minutes in Group C. Conscious sedation and dental
      treatment were achieved in 79%, 96% and 100% of the children in Groups A, B and
      C, respectively. Consistently higher Houpt scores were seen in Groups B and C,
      with statistically significant differences between Groups A and C, and B and C
      (Tukey's range test, P < 0.05). There were no significant differences in the
      general behaviour of the child, the onset and the duration of sedation between
      the fasting and the non-fasting child (nonparametric ANOVA P > 0.05). All the
      vital signs were within normal physiological limits and there were no significant
      adverse effects either with or without fasting. CONCLUSIONS: All 3 doses of
      intranasal midazolam were effective in modifying the behaviour of the
      uncooperative child patient to accept dental treatment. This was irrespective of
      fasting.

PMID- 11309872
TI  - Children choosing between general anaesthesia or inhalation sedation for dental
      extractions: the effect on dental anxiety.
AB  - AIM: To compare the levels of dental anxiety experienced by children having
      dental extractions using general anaesthesia (GA) with those having extractions
      using local anaesthesia and inhalation sedation (IHS) when offered a programmed
      choice between the two techniques prior to treatment. DESIGN: Structured
      interview with child at pre-treatment and at one week (approximately) follow up.
      SETTING: Community: primary health care centre. SUBJECTS: Children aged 9-15
      years referred to a local NHS Trust dental clinic (n = 88). INTERVENTION: Child
      and parent provided with information about IHS and its benefits over GA for the
      assistance in tolerating extraction of teeth and provided with a choice of
      procedure. MAIN OUTCOME MEASURE: An eight question modified child dental anxiety
      scale. RESULTS: Full information was received from 76 children giving an 86%
      response rate. Post-operative dental anxiety was lower in children who had chosen
      (with their parent) IHS in comparison to those who had chosen general anaesthesia
      (P < 0.05). Dental anxiety remained unchanged in the group who chose to have
      their extractions under GA. CONCLUSION: Children and their parents who select IHS
      as opposed to GA to assist in extractions demonstrate less psychological
      distress.

PMID- 11309873
TI  - The influence of three Erbium:YAG laser energies on the in vitro microleakage of
      Class V compomer resin restorations.
AB  - OBJECTIVES: To investigate the influence of three Erbium:YAG pulse energies (200
      mJ, 240 mJ, and 300 mJ with a 100 mJ dentine finish) on the microleakage of Class
      V compomer restorations (Compoglass). DESIGN: In vitro study. SAMPLE AND METHODS:
      Sixty-one extracted human premolar teeth were randomly allocated to three groups
      (according to pulse energy). Each tooth hosted one test cavity prepared with one
      of the three Er:YAG pulse energies using a pulse repetition rate of 5 Hz and a
      pulse duration of 250 microseconds, and one control cavity prepared with a
      conventional diamond bur in a high-speed hand piece. Both cavities were placed at
      the cervical margin of the tooth and were restored and finished according to the
      manufacturer's instructions. Each tooth was then stored in 0.12% thymol solution
      at 37 degrees C for three months, before being thermocycled through water baths
      between 5 degrees C and 55 degrees C for 240 cycles. Microleakage was assessed
      using a methylene blue dye penetration technique and was quantified using a score
      0 (none) to 4 (to and into the axial wall). The data was analysed using the
      Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: Leakage was seen in all groups
      at both the dentine and enamel margins. There were no statistically significant
      differences in leakage (P < 0.05) at either the enamel or dentine margins, except
      for the 240 mJ lased enamel margins. This group performed significantly better
      than the enamel margins prepared with 200 mJ (P = 0.03) and the 300/100 mJ (P =
      0.01) laser energies as well as the conventionally prepared enamel margins (P <
      0.001). CONCLUSION: Cavity preparation with this Erbium:YAG laser did not
      influence the microleakage of Compoglass restorations adversely. Different pulse
      energies were required for optimum cavity sealing at the enamel and dentine
      margins and for different materials.

PMID- 11309874
TI  - A review of clinical features in 13 cases of impacted primary teeth.
AB  - AIM: The aim of this study was to review clinical findings in 14 impacted primary
      teeth in 13 cases treated at a Paediatric Dental Clinic over a period of 18
      years. METHOD: The retrospective study used clinical records, radiographs and
      oral photographs. Data included age, gender, presenting complaints, location,
      radiographic findings, aetiological factors, treatment and prognosis of impacted
      primary teeth and their permanent successors. RESULTS: The patients included five
      males and eight females aged from one year two months to seven years five months.
      One case had impacted bilateral, mandibular primary central incisors and the
      remaining 12 cases each had one impacted tooth. The maxillary second primary
      molar was the tooth most frequently involved. Permanent successor tooth germs
      were identified in 12 teeth but not in two. Five cases were impacted because of
      odontomas, in the case with bilaterally affected mandibular primary central
      incisors these were malpositioned and were erupting ectopically. In seven cases,
      aetiology was unknown. Four impacted primary teeth were extracted because
      eruption was unlikely. In four cases, odontomas were surgically removed and the
      teeth kept under observation. The remaining six were surgically exposed. Traction
      was applied in two of the six. Eight of the teeth erupted. In two teeth in which
      traction was used, one was subsequently extracted, and one erupted. In the cases
      of seven, permanent successors erupted. These were hypoplastic teeth and were
      delayed in development and eruption. CONCLUSIONS: Impacted primary teeth may be
      associated with defects in development and eruption of their permanent
      successors, long-term observation is therefore necessary until the permanent
      successors erupt.

PMID- 11309875
TI  - Spontaneous improvement in position of canines from apparently hopeless
      positions.
AB  - Two cases are presented, each with both unerupted maxillary canines so badly
      positioned that eruption seemed unlikely. However, over a period of approximately
      three years, three out of the four initially displaced canines did erupt; the
      improvements in position being unrelated to whether or not the associated primary
      canine was extracted. Three out of four primary canines were removed. These cases
      highlight the difficulties in predicting canine eruption for individual patients.

PMID- 11309876
TI  - Bilateral macrodontia of mandibular second premolars: a case report.
AB  - Macrodontia of single teeth is rare. This has been reported on only six occasions
      in scientific journals when affecting mandibular second premolars with associated
      morphological anomalies. The large crown size causes problems with eruption, and
      disrupts the dentition. There are consequent inherent difficulties for the
      extraction of these teeth. Once erupted, their anatomy predisposes them to
      caries. Most cases are seen in children, before interventive surgery has been
      completed. The morphological anomalies of these premolar Macrodonts appear quite
      distinct and may justify a separate unique categorization.

PMID- 11309877
TI  - Mucus extravasation phenomenon in newborn babies: report of two cases.
AB  - Two rare cases of congenital mucoceles in newborn babies are reported. The
      patients presented with nodular swellings on their lower lips at birth with no
      obvious local aetiology. In both cases the mucoceles interfered with normal
      feeding. The lesions were excised by surgical approach under general anaesthesia
      and histopathological examination confirmed the lesions to be extravasation-type
      mucoceles. The article includes a brief discussion of the epidemiology and
      ethiopathogeny of mucoceles.

PMID- 11309878
TI  - A maxillary protracting bow appliance for Class III treatment in the primary
      dentition.
AB  - The design of a simple facial mask type appliance for the treatment of Class III
      with anterior crossbite in the primary dentition, is described. Its clinical
      effect is illustrated in two cases. The appliance is easy to make, cheap, well
      tolerated and efficient.

PMID- 11309879
TI  - [An original experience: admittance to the Isle-Adam Hospital].

PMID- 11309880
TI  - [Day care of aged patients with Alzheimer's disease and related disorders].

PMID- 11309881
TI  - [Acute ischemia of the extremities].

PMID- 11309882
TI  - [Vegetables and fruits in the daily diet].

PMID- 11309883
TI  - [Equipment and quality of geriatric nursing care, reflexions of nurses].

PMID- 11309884
TI  - [Improving potentially painful nursing care].

PMID- 11309885
TI  - [Electroconvulsive therapy of the aged].

PMID- 11309886
TI  - [Keeping a journal a collective adventure].

PMID- 11309887
TI  - [Admission to day care hospital and complementary features].

PMID- 11309888
TI  - [Day-care hospital for the aged].

PMID- 11309889
TI  - [Geriatric coordination in the Canton of Guerande].

PMID- 11309890
TI  - [The Amareis association of geriatric information].

PMID- 11309891
TI  - [Epistaxis in the aged].

PMID- 11309892
TI  - [Nursing practice: body communication, touching, massage].

PMID- 11309893
TI  - [Role of the nurse in group therapy of the demented aged].

PMID- 11309894
TI  - [Diet dried fruit and vegetables source of well-being].

PMID- 11309895
TI  - [A bracelet for the detection of accidental falls in the aged].

PMID- 11309897
TI  - [Correcting coordination in geriatrics].

PMID- 11309896
TI  - [Quality assurance in old age homes, a culture shock].

PMID- 11309898
TI  - [Expectations of families of aged patients under long-term care].

PMID- 11309899
TI  - [19 networks of geriatric nursing as experienced by the MSA (Mutual Farmer's
      Association)].

PMID- 11309900
TI  - Meningococcal response team enhancing community health: a collaborative effort.

PMID- 11309901
TI  - Clinical notebook. Nursing assessment turns life around.

PMID- 11309902
TI  - Writing for publication.

PMID- 11309903
TI  - An overview of the management of recurrent breast cancer.
AB  - Breast cancer recurrence is a potential problem for anyone who is diagnosed with
      breast cancer. Recurrent breast cancer can manifest both locally and systemically
      and can cause a variety of symptoms. After a diagnosis is established, treatment
      and symptom management may include radiation, chemotherapy, surgery and hormone
      therapy. The confirmation of a recurrent diagnosis may have far-reaching
      psychological and social implications for the patient. The care of each patient
      with metastatic disease must be tailored to that individual's needs and will
      involve the varied skills of the multidisciplinary team. The type of care that is
      given should be negotiated with each patient, and includes a combination of
      active treatment and symptom management, with the ultimate aim of ensuring that
      the patient's quality of life is maintained at an optimum level for as long as
      possible.

PMID- 11309904
TI  - Central venous catheter management in patients with cancer.
AB  - This article provides a summary on the management of central venous catheters
      (CVCs) in the person with cancer. The use of CVCs is becoming more commonplace
      with the emphasis on home-based cancer therapies and the increasing use of high
      dose chemotherapy regimens and stem cell rescue. The different types of CVC are
      examined and the potential complications and nursing management are discussed in
      this article. Nurses are leading practice in this area, undertaking a holistic
      assessment of the patient before inserting a CVC that meets their specific
      medical and personal requirements. A thorough understanding of the use of CVCs,
      potential complications and patient issues is crucial for sensitive assessment
      and treatment.

PMID- 11309905
TI  - Discharge planning of terminally ill patients home from an acute hospital.
AB  - This exploratory descriptive study was designed to explore how well carers
      perceived they were being prepared by hospital staff to care for a terminally ill
      relative at home. In particular the study focused on the information and
      practical advice and support they received in hospital and how much this
      facilitated them in caring at home following the patient's discharge from
      hospital. The study used a convenience sample of 12 patients and carers referred
      to a specialist palliative care service in an acute teaching hospital. The data
      were collected using semi-structured interviews. Qualitative analysis identified
      an overarching theme and related categories on coping with caring at home. The
      findings are supported by Folkman's (1997) model of stress and coping and
      corroborated by other research on carers' needs (Davies et al, 1994; Fakhoury et
      al, 1997). Interventions that may enable health professionals to facilitate
      carers to cope more effectively in caring at home and recommendations for further
      study are discussed.

PMID- 11309906
TI  - Paediatric palliative care: a lack of research-based evidence.
AB  - Providing the best possible care for the child and family is paramount to health
      professionals working in paediatric palliative care. However, there is little
      research which enables practitioners to question their current practice. There
      are concerns about conducting research on children receiving palliative care at
      such a sensitive time for the child and his/her family. These concerns must be
      considered against the growing demand for clear standards and guidelines for
      practice within health care. According to the Department of Health (DoH) there is
      no place within the modern healthcare system for the adoption of unproven
      theories or outdated care (DoH, 1998). While no-one would question the dedication
      and care being delivered to children and their families by well-trained staff,
      the lack of research is a cause for concern. A group of students undertaking a
      degree module in paediatric palliative care identified the lack of literature and
      research in this area and have undertaken a review of the available literature.

PMID- 11309907
TI  - An audit of out-of-hours advice services provided by hospice staff.
AB  - For those giving and receiving health care there will always be problems and
      queries which occur outside of normal office hours. Palliative care is no
      exception. It was found that Queenscourt Hospice in Southport was being used as
      an accessible point of contact for specialist palliative care advice by patients,
      relatives and health professionals. In response, an audit was undertaken to
      monitor the frequency and substance of the many drop-in visits and telephone
      calls to the hospice. The results showed that almost half of the calls/visits
      received are outside office hours. This article describes the nature of the calls
      and the advice offered by the staff taking the call. As the majority of the 'out
      of-hours' calls/visits were taken by nursing staff, it was necessary for them to
      draw on their specialist palliative care knowledge and communication skills to
      make an assessment of how best to deal with each situation. As a result of the
      audit, several organizational and educational initiatives have been developed to
      further improve the service offered.

PMID- 11309908
TI  - Mindful messages: surfing for spirituality.

PMID- 11309909
TI  - Rhetoric or service: what are the real issues?

PMID- 11309910
TI  - The development of nurses as managers: the prevalence of the self-development
      route.
AB  - AIM: This article identifies ways in which hospital sisters and charge nurses
      (ward managers) are developed as managers in one London teaching hospital.
      CONTEXT: Ward managers are practising in the context of increasing management
      responsibility in which decision-making is being driven to occur as close to the
      patient as possible. Decision-making about the management development
      opportunities for ward managers rests with senior nurse managers who have
      espoused their own preferences about the styles of management development open to
      ward managers. METHODS: For this small-scale exploratory-descriptive study,
      qualitative research methods were used with a postal self-completed questionnaire
      followed by a focus group. The target population was a group of 22 senior nurse
      managers. There was a questionnaire response rate of 68% (n = 15 respondents,
      four of whom participated in the focus group). FINDINGS: The research exposed and
      substantiated four styles of management development. The organizational
      prevalence of these styles and the ward managers' preference for each style were
      also ascertained. The most prevalent style was the one for which there was the
      least preference. CONCLUSIONS: The findings indicated that there was a general
      mismatch between the style of management development prevalent in the
      organization and the style of management development preferred by the subjects.
      This left the ward managers generally to follow an unstructured self-development
      route. The use of a theoretical framework, expressed as a Reluctance-Readiness to
      Manage Continuum, is suggested to harness the propensity to self-develop and to
      link it with the organizational need to develop nurses as managers through the
      paradox of structuring self-development.

PMID- 11309911
TI  - Action research, change and methodological rigour.
AB  - AIM: To critically examine concepts of methodological rigour in action research
      and consider how these affect its capacity to enable change. KEY ISSUES: Action
      research is potentially attractive to managers of nursing because it is a problem
      focused approach. As action research is identified as a continuum of definitions
      and philosophies rather than a single approach, caution is expressed that the
      search for definition may obscure the underlying process of change. Issues of
      reliability and validity are explored, suggesting that concern for methodological
      rigour may limit the potential for change and improvement in practice. Ethical
      issues in action research are considered identifying areas for tension between
      researchers, managers and practitioners. Some examples of action research in
      nursing are discussed. CONCLUSION: Action research may be valuable in individual
      practitioners' development or in fostering collaboration between academe and
      practice. However the demands for methodological rigour in research limit its
      effectiveness as a strategy for managing change.

PMID- 11309912
TI  - Flogging the dead horse: the myth of nursing empowerment?
AB  - With the move towards a more 'open' National Health Service, a new deal for
      staff, and greater staff involvement the way ahead for nursing seems bright. The
      proposals in the governmental White Paper (1997) The New NHS: Modern, Dependable
      reflect the need for greater co-operation and for a greater empowerment of
      nurses. If the aims of such major change in the NHS are to be achieved we need to
      consider both the real effects of nursing empowerment from past history, and the
      problems involved in greater nursing involvement in the NHS as an organization.
      As such our discussion may throw some light on the possible ways to progress
      during such fundamental change. It is from such lessons that positive future
      progress may be made. Firstly a discussion of the concept and its relationship to
      health and effective self-image is considered. Opportunities in respect of
      changing environments, and a move to more transformational change within the NHS
      could allow greater empowerment and feelings of self-efficacy. Such large scale
      change is essentially cultural and attitudinal; central to governmental proposals
      for NHS reform. The authors consider the real effect of nursing empowerment;
      based in part on the work of Kanter (1993) in the USA and work on empowerment and
      the role of nursing; and of power relationships within the organization. The
      links with the nurse's role in primary care groups and clinical governance are
      strong, with subsequent lessons for the British nurse during these initial
      changes. The potential for positive benefit is high; but coupled with this is a
      discussion on the relationship of NHS management, and a brief analysis of
      managerial practice and attitude, which may mitigate against empowerment. The
      authors put the case that structural changes are not sufficient to allow greater
      empowerment; which in its present form may only be an ideal. A greater effort by
      all is required if the myth is to be made a true reality.

PMID- 11309913
TI  - Implementation of hospital care pathways for patients with schizophrenia.
AB  - AIM: This paper aims to discuss some of the issues for the implementation of care
      pathways for inpatients suffering from schizophrenia. This paper builds upon a
      previously published paper describing the development of the care pathway.
      BACKGROUND: The use of a care pathway may enable care to be delivered in a more
      efficient and effective way. Very little is known about the development or
      implementation of care pathways for mental health conditions. METHODS: Action
      research guided the process of implementation and led to 29 in-depth interviews.
      Participant observation and records of 15 working group meetings rounded the data
      analysis. FINDINGS: The nature of the study site changed dramatically over the
      course of the research programme with many staff leaving the ward. This led to
      many problems in implementing the care pathway including poor levels of morale
      and engagement; how the patients were admitted and managed on the care pathway;
      poor levels of documentation. CONCLUSIONS: The findings are particular to this
      research environment, although some wider issues could be applicable to other
      sites such as the nature of representing psychiatric work on the care pathway;
      the evidence-based practice movement and the role of the user and individualized
      care.

PMID- 11309914
TI  - Patient satisfaction and research-related problems (Part 1). Problems while using
      a questionnaire and the possibility to solve them by using different methods of
      analysis.
AB  - INTRODUCTION: This article comprises two parts describing a research project for
      validating quality monitoring tools. This is part 1. AIM: To examine the problems
      of patient satisfaction inquiries by means of the literature, earlier research
      and an example. BACKGROUND: The topic is of current interest, since quality
      management by way of research-based knowledge has become an increasingly common
      demand. In this context, patient satisfaction inquiries are a central method of
      data collection. Although the problems relating to the reliability of the methods
      and results of these inquiries have been identified, their comprehensive
      examination is yet to be done. Quality management is none the less a challenge to
      nursing administrators requiring a broad-based utilization of feedback data, and
      this calls for a critical examination of the reliability of these results.
      METHODS: The exemplary material were collected using a questionnaire from
      patients (n = 282) on three different hospital wards. Different statistical
      methods and content analysis were used in the analysis. FINDINGS: The example
      used in the study indicates that the results of the inquiry were highly positive
      time after time. The reliability of the instrument presented a problem. The low
      amount of information collected in the open-ended question was another problem
      that can be criticised in relation to the amount of work required in the
      analysis. The results of the factor analysis showed that the questionnaire needs
      further development. CONCLUSIONS: To conclude, patient satisfaction inquiries
      yield a relatively small and limited amount of information on quality management
      and improvement, but this information is necessary specifically for ward sisters
      for the follow-up of long-term trends in patient satisfaction. The second part of
      this article (part 2) examines the description of patient satisfaction by means
      of triangulation.

PMID- 11309915
TI  - Patient satisfaction and research-related problems (Part 2). Is triangulation the
      answer?
AB  - AIM: The article consists of two parts, the first of which examined the
      description of patient satisfaction by means of a questionnaire and the problems
      related to it. The aim of this second part is to complement the topic by
      explicating patient satisfaction research using a triangulative approach.
      BACKGROUND: Patient satisfaction has been the object of interest in health care
      for some time, and is now increasingly used as the basis for quality management
      and improvement. At the same time, the methods used have been criticised. As it
      was shown in the first part of this article, traditional questionnaires contain
      many problems which are difficult to solve in a satisfactory way, for example, by
      using different methods of analysis. METHODS: The data were collected from the
      patients of three different hospital wards using an interview (n = 30). The
      interview themes corresponded to the classification of a questionnaire employed
      at the same time. The interview material was analysed using content analysis,
      whereas satisfaction is investigated using a triangulative approach. FINDINGS:
      The findings confirm that the interview supplements the questionnaire as a data
      collection method, but that is also produces overlapping information. The
      interviews gave deeper information on the patients' experiences and feelings.
      Triangulative examination made it possible to show factors influencing the
      reliability of the study. CONCLUSIONS: The advantage of a triangulative approach
      seems to be that it provides a fairly accurate description of patient
      satisfaction. However, the problem of this method is that it doubles the amount
      of work needed and is slow to use which is worth considering as patient
      satisfaction should be followed on a regular basis and the results reported
      without delay. In spite of these problems, patient satisfaction surveys are
      important, since information provided by them is needed as basis for quality
      management, quality improvement and clinical supervision.

PMID- 11309916
TI  - What's your problem?

PMID- 11309917
TI  - It's what we do next that counts.

PMID- 11309918
TI  - At the sharp end.

PMID- 11309919
TI  - Aftershock.

PMID- 11309920
TI  - A winning lead.

PMID- 11309921
TI  - Free spirit.

PMID- 11309922
TI  - Passing it on.

PMID- 11309923
TI  - Keep the gold watch.

PMID- 11309924
TI  - Mental health services for older people.

PMID- 11309925
TI  - Psychological effects of source isolation nursing (2): Patient satisfaction.
AB  - AIM: This study is part two of a research project (Davies and Rees 2000) aiming
      to investigate the relationship between mood, patient satisfaction and a range of
      quality of care factors among patients nursed in source isolation in acute and
      rehabilitation settings. METHOD: A small audit-style evaluation of aspects of the
      overall clinical care of patients nursed in isolation. Twenty one patients being
      nursed in source isolation were interviewed to assess factors relating to
      delivery of care. RESULTS: The authors noted frequent mood disturbances among
      isolated patients, although most were generally satisfied with their care and
      surroundings. Factors associated with patient satisfaction included being kept up
      to date with progress and procedures, having a comfortable environment and good
      communication between staff and patients. CONCLUSION: The authors suggest that
      staff training should include consistent use of verbal and written information.
      The patients should be allowed access to telephone and television, and their
      surroundings should be kept clean.

PMID- 11309926
TI  - The use of soap operas in nurse education.
AB  - Storylines about health issues are common in non-medical soap operas. It is not
      clear whether they are included primarily for their dramatic value, or if there
      is an intention to raise awareness of a particular health issue. The aim of this
      article is to provide a rationale for the use of soap operas in the classroom
      and, whether intentional or otherwise, how the issues raised can be used
      specifically in the education of nurses.

PMID- 11309927
TI  - Who needs vitamin and mineral supplements?
AB  - The use of vitamin and mineral supplements is growing rapidly. This article
      describes the effects of common supplements and asserts that for most people,
      they are an unnecessary waste of money. However, they can be a useful adjunct to
      the diet for certain vulnerable groups.

PMID- 11309929
TI  - Care of the patient with a sexually transmitted disease.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Alison Woodland
      discusses sexually transmitted diseases. Article NS 2. Wright S (1999) Sexually
      transmitted diseases. Nursing Standard. 13, 46, 37-42.

PMID- 11309928
TI  - Cultural and religious influences on adult nutrition in the UK.
AB  - The UK is a multicultural society where the prevalence of nutrition-related
      illnesses varies between different cultures. In this article, the common cultural
      and religious influences on diet are identified and healthy choices recommended.

PMID- 11309930
TI  - Sources of inspiration.

PMID- 11309931
TI  - Calling all people people.

PMID- 11309933
TI  - Beware the charm and promises.

PMID- 11309932
TI  - Management of leg ulcers.

PMID- 11309934
TI  - Distinctly valuable.

PMID- 11309935
TI  - All talk, little action.

PMID- 11309936
TI  - Unlicensed to kill.

PMID- 11309937
TI  - Until we tempt back experienced nurses, agencies will always do good business.

PMID- 11309938
TI  - Protection racket.

PMID- 11309939
TI  - They are. Are you?

PMID- 11309940
TI  - Gynaecology nursing.

PMID- 11309941
TI  - Spiritual experience or religious psychosis?

PMID- 11309942
TI  - Cognitive deficits in schizophrenia.

PMID- 11309943
TI  - Evidence-based nursing for older people.

PMID- 11309945
TI  - Best behaviour: how to get evidence into practice.

PMID- 11309944
TI  - Nurses' experiences as patients' relatives.

PMID- 11309946
TI  - Managing transition. 1.

PMID- 11309947
TI  - Systems and diseases. The heart, Part Ten. Heart failure-2.

PMID- 11309948
TI  - Family fortunes.

PMID- 11309949
TI  - Jim'll fix it.

PMID- 11309950
TI  - How come we're losing if we scored the equaliser?

PMID- 11309951
TI  - Vive la difference: that's what will make collaboration work.

PMID- 11309952
TI  - Where do nurse practitioners leave us?

PMID- 11309953
TI  - Our hollow claim to care.

PMID- 11309954
TI  - Nursing's leaders must take Mr Milburn at his word and lever for change.

PMID- 11309956
TI  - Where you fit into our vision.

PMID- 11309955
TI  - Nursing by numbers.

PMID- 11309957
TI  - Community teamwork is key to monitoring the side-effects of medication.

PMID- 11309958
TI  - Learning to collaborate.

PMID- 11309959
TI  - Role of specialist nurses in follow-up cancer care.

PMID- 11309960
TI  - Who should see 'extras'?

PMID- 11309961
TI  - Cost of care in general practice.

PMID- 11309962
TI  - Nurse-led service for minor conditions.

PMID- 11309963
TI  - Proactive health care for men over 65.

PMID- 11309964
TI  - Legal and accountability issues.

PMID- 11309965
TI  - Central venous pressure measurement.

PMID- 11309966
TI  - Have qualifications, will travel.

PMID- 11309967
TI  - Care closer to home.

PMID- 11309968
TI  - Primary colours.

PMID- 11309969
TI  - The right to leave.

PMID- 11309970
TI  - Mental wealth.

PMID- 11309971
TI  - Growing concern.

PMID- 11309972
TI  - Pie-eyed and deskless.

PMID- 11309973
TI  - Table manners.

PMID- 11309974
TI  - Special powers.

PMID- 11309975
TI  - Don't be complacent.

PMID- 11309976
TI  - Research ethics.

PMID- 11309977
TI  - Post-operative nausea and vomiting: a survey of nurses' knowledge.
AB  - Many patients experience the discomfort of post-operative nausea and vomiting.
      This article reports on a survey to find out just how much nurses know about
      relieving these distressing symptoms.

PMID- 11309979
TI  - Pain management for patients with chest drains.
AB  - The management of pain for patients with chest drains has been largely neglected.
      This article reviews the evidence and describes how applying a theoretical model
      can help patients undergoing this painful invasive procedure.

PMID- 11309978
TI  - Visitors' violence: the serious effects of aggression on nurses and others.
AB  - Nurses are well aware of the potential threat of violence from patients, but
      attacks by visitors are now increasingly common. This article suggests this form
      of violence is often overlooked, but has long-term negative effects on staff
      morale.

PMID- 11309980
TI  - Wounds and pain management.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Karen McDowell
      discusses wound management and pain control. CPD article NS14, Gould D (1999)
      Wound management and pain control. Nursing Standard. 14, 6, 47-54.

PMID- 11309981
TI  - A step in the right direction.

PMID- 11309982
TI  - Handling training.

PMID- 11309984
TI  - Strength in numbers.

PMID- 11309983
TI  - Work, rest and play.

PMID- 11309985
TI  - The most vulnerable.

PMID- 11309986
TI  - Community channels.

PMID- 11309987
TI  - We don't have to take this: dealing with violence at work.
AB  - The Health and Safety Executive has identified nursing as the most hazardous
      occupation in the United Kingdom. Nurses are more likely to be on the receiving
      end of violence than policemen (HSC 1997); violence remains constant for
      employees in healthcare. Most days there are news reports of violent incidents
      being perpetrated against nurses, doctors or other NHS staff. If such incidents
      are not dealt with adequately, the consequences can be devastating, not only in
      terms of physical injury to the victim, or psychological trauma as a result of
      verbal abuse, but in terms of morale and staff performance. As they come face to
      face with violence, nurses may feel increasingly isolated, unsupported and
      uncared for. This workbook aims to provide clear guidelines for assessing the
      risk and dealing with the hazard of violence for managers and nurses. The menace
      of violence in healthcare may never be eliminated completely, but there are
      things that can be done to manage, and therefore reduce the problem.

PMID- 11309988
TI  - Ophthalmic millennium projects of peace and war.

PMID- 11309989
TI  - How to prepare your office for medical emergencies.

PMID- 11309990
TI  - Corneal topography and wavefront analyzers in the new century.

PMID- 11309991
TI  - Understanding dry eye.

PMID- 11309992
TI  - Experts' five tips on routine use of punctum plugs.

PMID- 11309993
TI  - Complications due to misuse of plugs?

PMID- 11309994
TI  - Pretreatment and posttreatment care of LASIK patients.

PMID- 11309995
TI  - Basic manual lensometry: a guide for measuring distance and near glasses.
AB  - Manual lensometry is a basic component of ophthalmic clinical care. You will find
      it necessary to check lens prescriptions manually when the written prescription
      does not match the results of an automated lensometer or when automated
      lensometry is not available.

PMID- 11309996
TI  - Inhibitors of neovascularization.
AB  - The use of neovascular inhibitors in the treatment of CNV will no doubt have a
      profound impact in the future. However, complex issues surround the use of these
      agents. Careful clinical trials will be necessary to determine the optimal
      parameters for their use. Furthermore, it must be determined whether these
      inhibitors will be most efficacious as primary agents or as agents used to
      augment the efficacy of photoreactive laser treatment or feeder vessel treatment.

PMID- 11309998
TI  - Proper positioning can avoid height error.

PMID- 11309997
TI  - Traumatic optic neuropathy in a newborn.

PMID- 11309999
TI  - Infection and the contact lens wearer.

PMID- 11310000
TI  - Perception of stressors of hospitalized patients.

PMID- 11310001
TI  - Discipline in the work place.

PMID- 11310002
TI  - Pharmacology departmental update.

PMID- 11310003
TI  - Scientists, educators, patient advocates ... clinical trial nurses play many
      roles.

PMID- 11310004
TI  - . . . clinical trials offer the potential for better care.

PMID- 11310005
TI  - Clinical trials are just a click away.

PMID- 11310006
TI  - Groups support insurance coverage for clinical trials.

PMID- 11310007
TI  - Pay and dismay: hospital hell.

PMID- 11310008
TI  - Pay and dismay: community woes.

PMID- 11310010
TI  - The wards are alive with the sound of sermons.

PMID- 11310009
TI  - Should nursing become a graduate-entry profession?

PMID- 11310011
TI  - A whole world in your hands.

PMID- 11310012
TI  - Contracting out is a dirty business.

PMID- 11310014
TI  - Blinded by the facts.

PMID- 11310013
TI  - Manhattan madness.

PMID- 11310015
TI  - NHS Direct will not cure ward-level staffing and skill-mix problems.

PMID- 11310016
TI  - You can't beat togetherness.

PMID- 11310018
TI  - How dare they treat me like that.

PMID- 11310017
TI  - Double take.

PMID- 11310019
TI  - Managing pain in paediatrics.

PMID- 11310020
TI  - Meningitis: a rash diagnosis.

PMID- 11310021
TI  - Assessing flu patients.

PMID- 11310022
TI  - Accessible health sessions for first-time fathers.

PMID- 11310024
TI  - Reflection in supervision.

PMID- 11310023
TI  - Hand hygiene for patients with rheumatic diseases.

PMID- 11310025
TI  - Systems and diseases. The heart, Part Nine.

PMID- 11310026
TI  - There to tide people over.

PMID- 11310027
TI  - Taking it to the limit.

PMID- 11310028
TI  - Contradiction in terms.

PMID- 11310029
TI  - Country life.

PMID- 11310030
TI  - Positive thinking.

PMID- 11310031
TI  - Hi-tech but friendly.

PMID- 11310032
TI  - Mum's the word.

PMID- 11310033
TI  - Stand and deliver.

PMID- 11310034
TI  - Our ailing health service.

PMID- 11310035
TI  - Establishing a research nurses' forum.

PMID- 11310037
TI  - The neurogenic bladder.
AB  - Many people with incontinence and bladder problems have an underlying neurogenic
      cause, with damage to the neurological pathways which regulate the function of
      the bladder. This article demonstrates how an understanding of the neurological
      control of the bladder can lead to more effective assessment and treatment of
      incontinence.

PMID- 11310036
TI  - Patient satisfaction with post-operative analgesia.
AB  - AIM: The aim of this study was to compare intravenous and epidural analgesia for
      patients undergoing total knee replacements. Side effects of analgesia were
      assessed to see whether they influenced patient satisfaction. METHOD: Patients
      were randomly allocated to either the intravenous or epidural group. Their
      experience of pain was assessed using visual analogue scales and a questionnaire.
      RESULTS: There was no evidence to support claims that epidural analgesia provides
      more consistent pain relief and more rapid rehabilitation. There was no
      correlation between length of stay and the route by which post-operative
      analgesia was administered. CONCLUSION: Patients undergoing total knee
      replacement can have their post-operative pain equally well controlled with
      either intravenous or epidural analgesia.

PMID- 11310038
TI  - Healthy eating: something to chew over?
AB  - Most of us probably feel that we know enough about healthy eating and fibre in
      the diet; after all we have been advising people to eat more of it for years. But
      do we know all that we should? Alison Sullivan provides an update on the latest
      dietary recommendations.

PMID- 11310040
TI  - Safe use of pulse oximetry.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles. This week Ruth Garner discusses
      pulse oximetry. Article no. 501. Woodrow P (1999) Pulse oximetry. Nursing
      Standard. 13, 42, 42-46.

PMID- 11310039
TI  - Post-traumatic stress disorder.
AB  - Post traumatic stress disorder affects up to 1 per cent of the population, yet
      there are few specially trained nurses who are able to offer appropriate care and
      treatment. This article explores this condition, its treatment and the need for
      more suitably qualified nurses to fill this gap.

PMID- 11310041
TI  - Cream of Guernsey.

PMID- 11310042
TI  - A passage to practice.

PMID- 11310043
TI  - Is the Saving Lives public health agenda failing?

PMID- 11310044
TI  - Don't kill off Dr Finlay.

PMID- 11310045
TI  - Three steps to eliminate racism.

PMID- 11310047
TI  - Dead men walking.

PMID- 11310046
TI  - Man troubles.

PMID- 11310048
TI  - Telling porkies about what nurses earn has turned into a PR bungle.

PMID- 11310049
TI  - Boy story.

PMID- 11310050
TI  - Is giving medication without consent ethical?

PMID- 11310051
TI  - Going concerns.

PMID- 11310052
TI  - The case for independent nurse managers.

PMID- 11310053
TI  - Taking school nursing into the community.

PMID- 11310054
TI  - The care pathway approach in an acute mental health inpatient unit.

PMID- 11310055
TI  - Adolescent and adult immunisation: overview.

PMID- 11310056
TI  - Babies who cry persistently: responses and prevention.

PMID- 11310057
TI  - NT open learning: clinical supervision--Part 8. Implementation problems.

PMID- 11310059
TI  - Because they're worth it.

PMID- 11310058
TI  - Central venous catheterisation--1.

PMID- 11310060
TI  - Colour-coded care.

PMID- 11310061
TI  - Walk the talk.

PMID- 11310062
TI  - Ring of confidence.

PMID- 11310063
TI  - It's a tough job.

PMID- 11310064
TI  - Count me in.

PMID- 11310066
TI  - A matter of trust.

PMID- 11310065
TI  - Burden of guilt.

PMID- 11310067
TI  - Research and practice development in the West Midlands region.

PMID- 11310068
TI  - Psychological effects of isolation nursing (1): Mood disturbance.
AB  - AIM: This study is part one of a research project aiming to investigate the
      relationship between mood disturbance and a range of quality of care factors
      among patients nursed in source isolation in acute and rehabilitation care
      settings, and to assess the accuracy of clinical staff's recognition of such
      disturbance. METHOD: A small audit-style evaluation of aspects of the overall
      clinical care of patients nursed in isolation. The findings reported here are the
      preliminary results of a larger study (Rees et al 2000). RESULTS: More than half
      of the sample was suffering from mood disturbance, and depression appeared to be
      under recognised by staff. There was a trend for higher anxiety scores to be more
      strongly associated with antidepressant prescription. CONCLUSION: Mood
      disturbance is a significant consequence of source isolation in patients, however
      healthcare staff have poorer recognition and treatment of depression than
      anxiety. Nurse education should include identification of disturbed mood,
      discrimination between depressed and anxious mood, and development of treatment
      protocols.

PMID- 11310069
TI  - Organ donation: the debate.
AB  - A resolution due to be debated at the RCN's annual congress in Bournemouth next
      week will ask members to 'urge the government to introduce an opt-out system of
      organ donation' (RCN 2000). The resolution will be preceded by a fringe event
      that will open up the debate. This article highlights some of the key issues.

PMID- 11310071
TI  - Infection control.
AB  - Dee May looks at the prevalence and cost of hospital-acquired infection, how
      epidemiological changes have influenced the way infections are prevented and
      managed, and how, in practice, infection should be controlled.

PMID- 11310072
TI  - Care of the ventilated patient.
AB  - Practice profiles are reflective pieces written by nurses in practice and based
      on continuing professional development articles.  This week Laura Coates
      discusses mechanical ventilation.  Article No. 503. Henderson N (1999) Mechnical
      ventilation.

PMID- 11310073
TI  - Searching for a fit definition.

PMID- 11310070
TI  - Preceptorship in practice.
AB  - Following a review of preceptorship practices within the children's services
      directorate of the Newcastle upon Tyne Hospitals NHS Trust, a working party was
      established to produce a directorate-wide preceptorship package. This article
      reviews the literature, provides a summary of the preceptorship guidelines, and
      critically analyses the process of implementing the programme.

PMID- 11310074
TI  - The pain killers.

PMID- 11310075
TI  - The measure of success: a mentoring project.

PMID- 11310076
TI  - Expanding the role of the perioperative educator.
AB  - Perioperative educators mostly conduct orientation, in service and continuing
      education to perioperative staff. Their role can be expanded to improve the
      quality and efficiency of perioperative care. To this end, an organizational
      communication model can be used to identify weaknesses and guide intervention. To
      be effective with this approach, perioperative educators have to work closely
      with perioperative managers.

PMID- 11310077
TI  - President's message. Basic principles.

PMID- 11310078
TI  - Creutzfeldt-Jakob disease guidelines: a regional approach.
AB  - Creutzfeldt-Jakob Disease (CJD) is an infectious, progressive, degenerative
      neurological disorder. Unique CJD Precautions must be adhered to as the
      infectious agent is difficult to destroy. A regional group in Hamilton-Burlington
      Ontario developed CJD guidelines based on critical review of the current evidence
      of transmission in a Canadian healthcare environment, current published standards
      of practice in North America, the United Kingdom and Australia; and principles of
      laboratory and patient care safety as well as expert opinion.

PMID- 11310079
TI  - Preventing foreseeable tragedy.

PMID- 11310080
TI  - Applying clinical practice guidelines to a patient with complicated
      gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a complex, often misunderstood disease
      that requires comprehensive medical and nursing care. Recently published clinical
      practice guidelines provide new direction with regard to the causes, diagnosis,
      treatment, and nursing care of patients with GERD. Using a case study approach,
      this article outlines the most recent evidence-based treatment options and
      patient education guidelines for a patient suffering from a complicated case of
      GERD.

PMID- 11310082
TI  - Autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a necro-inflammatory disease that, untreated,
      carries a 3-year mortality rate of approximately 50%. In this last of a series of
      three articles, current knowledge regarding AIH is reviewed. The mode of
      presentation of AIH is variable: insidious onset with few if any symptoms,
      presenting with symptoms indistinguishable from that of any acute viral
      hepatitis, or onset with fulminate hepatitis. In AIH, hepatocytes become injured
      by various agents (such as a viral infection) and become antigenic, leading to a
      self-perpetuating antigen-antibody response with subsequent chronic liver
      disease. AIH is the only type of hepatitis that is responsive to corticosteroids.
      Occasionally, AIH develops after liver transplantation.

PMID- 11310083
TI  - Responses of people with inflammatory bowel disease to foods consumed.
AB  - The purpose of this study was to assess the reactions of people with IBD to foods
      consumed. A database was created to capture the season of data collection, the
      disease, the food, and the subject's reaction to each food. A 122-item food list
      was used. Sixty patients with IBD (n = 33 persons with Crohn's disease, n = 27
      persons with ulcerative colitis) completed the questionnaire about foods and
      their reactions to the foods in the fall and spring representing summer and
      winter consumption. Foods that made the subjects feel better and worse were
      identified. Although the original purpose of the study was to assess people with
      IBD as a group, it became apparent that reactions to foods were different
      according to whether a subject had Crohn's disease or ulcerative colitis. Failure
      to distinguish between the two diseases and use only the pooled data made the
      data meaningless. The importance of this finding and themes related to foods that
      had a positive or negative effect on the subjects is discussed in this article.

PMID- 11310085
TI  - Standards of infection control in reprocessing of flexible gastrointestinal
      endoscopes.

PMID- 11310081
TI  - Effects of a single music therapy intervention on anxiety, discomfort,
      satisfaction, and compliance with screening guidelines in outpatients undergoing
      flexible sigmoidoscopy.
AB  - Screening flexible sigmoidoscopy (FS) is an effective tool for the detection of
      colon cancer. Nonetheless, persons are reluctant to undergo FS for a variety of
      reasons such as anxiety, discomfort, and the possibility of abnormal findings.
      Nurses caring for FS patients can implement interventions to allay anxiety and
      promote comfort in an effort to enhance satisfaction and future compliance. Music
      therapy is one nonpharmacologic intervention that has been shown to be effective
      in allaying anxiety, reducing discomfort, and promoting satisfaction in other
      patient populations. A two-group pretest, posttest experimental design with
      repeated measures study recruited 64 subjects undergoing FS from one Midwestern
      tertiary care center. Subjects were randomly assigned to a control condition of
      usual procedural care or to an experimental condition of music therapy during the
      examination. State and trait anxieties were measured at pretest. State anxiety,
      discomfort, satisfaction, and perceived compliance with future screening were
      measured after the procedure. Subjects in the music group reported less anxiety
      and discomfort than subjects in the control group. There were no differences on
      satisfaction ratings or perceived compliance with screening guidelines. Nurses
      caring for patients undergoing screening FS can offer music therapy as one
      nonpharmacologic intervention to ameliorate anxiety and reduce discomfort.

PMID- 11310084
TI  - Measles vaccination a risk factor for inflammatory bowel disease?
AB  - It has been postulated that measles virus or receipt of the measles vaccination
      may pose a risk to developing inflammatory bowel disease (IBD). This article
      presents a review of the literature discussing the measles virus as a possible
      risk factor for IBD. No data have confirmed this suspicion, and vaccination from
      measles virus should be strongly encouraged.

PMID- 11310086
TI  - Guideline for the use of high-level disinfectants and sterilants for reprocessing
      of flexible gastrointestinal endoscopes.
AB  - Glutaraldehyde, 0.2% peracetic acid, 7.5% hydrogen peroxide, 0.08% peracetic
      acid/1% hydrogen peroxide, and 0.55% ortho-phthalaldehyde are cleared by the FDA
      for reprocessing flexible gastrointestinal endoscopes. Each product has
      advantages and disadvantages. All require adherence to published reprocessing
      protocols in order to maintain the integrity of equipment while providing the
      public with endoscopic instruments that are safe and effective. All chemicals
      must be handled with respect. Selection of a product must be weighed against the
      needs of a particular setting, taking into consideration factors such as
      compatibility, toxicity, environmental controls and cost.

PMID- 11310087
TI  - Renewal: when you're "all cheered out".

PMID- 11310089
TI  - The new kid on the block.

PMID- 11310088
TI  - Complementary health care practices.

PMID- 11310091
TI  - Glandular odontogenic cyst. A rare entity with aggressive biological behaviour. A
      case report.
AB  - Glandular Odontogenic cyst is an apparently rare jaw cyst characterised by
      typical histopathological features, propensity to reach large size and high rate
      of local recurrence, if not adequately treated. Identification of this cyst as a
      separate entity is important because of the difference in biological behaviour.
      We report a case of Glandular Odontogenic cyst occurring in maxilla.

PMID- 11310090
TI  - Micronuclei in oral squamous cell carcinoma. A marker of genotoxic damage.

PMID- 11310092
TI  - A new nomenclature for oral and maxillofacial surgery that is facial and oral
      surgery.
AB  - To assess whether majority of the public and medical professionals do understand
      the field Oral & Maxillo-Facial Surgery. To find this, a questionnaire was
      devised based on P. Ammerally et al. 200 members of the public with educated
      background and 100 general medical practitioners participated in this study. The
      results revealed that majority of the public needed more information on the field
      where as the General medical practitioners were aware, but lacked information
      about the majority of activity in the field.

PMID- 11310093
TI  - Transparent tooth model system. An aid in the study of root canal anatomy.
AB  - Clearing techniques of tooth have long since been advocated in the demonstration
      of root canal anatomy. We have compared the efficacy of various clearing agents
      such as Xylene, Benzene, Methyl salicylate and Eugenol, using 40 maxillary second
      premolars as experimental subjects. We have further tried to select a suitable
      dye for the demonstration of root canal anatomy and have compared the efficacy of
      various mounting media such as D.P.X. medium, Canada balsam and Commercial
      plastic dissolved in benzene, in preserving the cleared state. Results of our
      study indicate that Eugenol is a superior clearing agent and that oil-based dyes
      are better suited for root canal demonstration. Canada balsam is the most
      effective mounting media and D.P.X. medium has been found to serve both as a
      clearing agent and as a mounting media. We have introduced a miniature museum jar
      technique, for preserving the transparency permanently. The Transparent Tooth
      Model System presented here, thus serves as a much simpler tool, in the study of
      root canal anatomy, three dimensionally.

PMID- 11310094
TI  - Enamel matrix derivative in periodontal reconstructive surgery. A new approach in
      periodontal regeneration.
AB  - True periodontal regeneration is the goal of any periodontal regenerative
      techniques. Cementum formation is a key event in the development of root and
      supporting periodontium. Due to its distribution, acellular cementum is the type
      most affected by early to moderate periodontitis. Studies over the past twenty
      years demonstrated that, enamel matrix proteins from the root sheath are involved
      in the formation of acellular, during tooth development. Thus the adjunctive use
      of enamel matrix derivatives in conjunction with regenerative periodontal surgery
      could possibly lead to true periodontal regeneration. The purpose of this article
      is to review the use of enamel matrix derivative in true periodontal
      regeneration.

PMID- 11310096
TI  - A comparison of post-operative morbidity following outpatient dental care under
      general anaesthesia in paediatric patients with and without disabilities.
AB  - An investigation was undertaken of morbidity after outpatient general anaesthesia
      for comprehensive dental care in a group of paediatric patients over a 1-year
      period. Data were collated from the patient's hospital notes and from the
      response to a questionnaire sent to parents/carers. Clinical data were obtained
      for 55 cases (age range 3-17 years) for whom parents/carers had returned
      questionnaires. There were 27 intellectually and/or physically impaired patients,
      the other 28 being anxious or phobic. After discharge, 44% of all parents/carers
      reported symptoms post-operatively in their child, the prevalence being similar
      in both groups. The symptoms were nausea/vomiting (20%), unexpected drowsiness
      (13%) and the need for pain relief at home (13%). Dental procedures were routine
      restorations (42%), or a combination of restoration, extractions and preventive
      care for the remainder. Only four patients had extractions only. One teenager had
      to be admitted for persistent nausea and vomiting, despite prophylactic measures.
      In conclusion, post-operative morbidity appears to be low after outpatient
      general anaesthesia for dental procedures, and is no greater in patients with
      disabilities.

PMID- 11310095
TI  - Oral health in children undergoing liver transplantation.
AB  - AIMS: To determine the prevalence of dental caries in children undergoing liver
      transplantation and to compare the plaque, gingivitis, and gingival overgrowth
      indices and oral mucosal lesions in children before and after liver
      transplantation. PATIENTS AND METHODS: Patients undergoing liver transplantation
      at King's College Hospital were examined before transplantation, at 3 and 106
      days post-transplantation. Healthy children from the Greenwich Health District,
      south-east London, were matched to the liver transplant patients by age, gender,
      socio-economic factors and the presence or absence of active dental caries.
      RESULTS: Twenty-seven liver transplant patients (mean age: 7 years and 10 months;
      SD 3 years and 5 months) and 27 controls (mean age: 8 years and 6 months; SD 3
      years and 7 months) were examined. The mean dmft and DMFT scores were 2.3 (SD
      4.1) and 0.8 (SD 1.4), respectively, in the liver transplant patients, and 1.2
      (SD 2.2) and 0.9 (SD 1.5), respectively, in the controls. There were no
      significant differences between either the mean plaque or gingivitis indices for
      the primary and permanent teeth in patients before and after transplantation.
      There were no significant differences between the liver transplant patients and
      the controls for either mean plaque or gingivitis indices at each examination
      time. Gingival overgrowth was present in 41% of liver recipients receiving
      cyclosporin with or without nifedipine, but not in the majority receiving
      tacrolimus at the final examination. Oral mucosal lesions were absent in both the
      patients and controls at each examination time. CONCLUSIONS: The oral health of
      the children undergoing liver transplantation was inadequate. Funding and
      implementation of an oral health care programme must become a priority for all
      children before and after liver transplantation.

PMID- 11310097
TI  - Dental anxiety among young adolescent patients in Israel.
AB  - AIM: To evaluate adolescents' dental anxiety using self-reported questionnaires
      previously given to adults. SAMPLE AND METHOD: One hundred and four patients (42
      boys, 62 girls) aged 12-18 years who attended their paediatric dentist completed
      a questionnaire in the waiting room. The survey consisted of three sections:
      sociodemographic information for the children, a dental anxiety scale (DAS), and
      a dental fear survey (DFS). RESULTS: The scores of the girls were higher than the
      boys in every DAS item as well as in the total score. Girls showed higher DFS
      scores than boys in most items. The most anxiety-provoking stimuli were feeling
      and seeing the needle. In the most anxiety provoking stimuli, among the boys who
      reported higher DFS scores (categories 3, 4, 5), the DAS scores were higher than
      the scores of the girls. As the stimulus became less anxiety-provoking, such as
      sitting in the dental chair, the DAS scores of the girls in these categories were
      higher than boys. Significantly more girls' responses were in categories 3, 4 and
      5 in the items dealing with the needle and the drill, while no significant
      difference was observed among the boys and girls regarding sitting in the dental
      chair. CONCLUSIONS: It is concluded that individual personality traits may be the
      final factor to indicate those who will eventually develop higher dental anxiety,
      and those who will not. The difference could be also in the conditioning process
      and learned responses (male and female education) that these individuals have
      experienced in life.

PMID- 11310098
TI  - Community dental officers' use and knowledge of restorative techniques for
      primary molars: an audit of two Trusts in Wales.
AB  - OBJECTIVE: A baseline audit of current levels of knowledge about, and use of,
      restorative techniques in children's primary molars. DESIGN: A survey of
      community dental officers. SETTING: Two large Trusts in Wales. SAMPLE: Eighteen
      dental officers (five from Trust A and 13 from Trust B) from a total of 23 (six
      from Trust A and 17 from Trust B). OUTCOME MEASURES: Dental officers' use of
      restorative materials in primary molars. Dental officers' participation in
      postgraduate training for restorative techniques. Dental officers' consideration
      of the research literature on 'best practice' in restorative techniques. RESULTS:
      Dental officers in these two Trusts were not using stainless steel crowns (SSCs)
      for restoring primary molars. All 18 dental officers reported using glass ionomer
      cement (GIC) and amalgam as restorative materials, whilst six reported using GIC
      exclusively. Only 11 dentists mentioned using stainless steel crowns and this was
      in conjunction with carrying out a pulpotomy. Fewer dentists had been taught to
      use GIC than either SSCs or amalgam for restoring primary teeth during
      undergraduate training. A hands-on, user-friendly, postgraduate training course
      is considered the most effective way of teaching dentists about restorative
      techniques. The research evidence on SSCs did not appear to influence these
      dental officers in their use of restorative materials. CONCLUSIONS: This study
      offers important baseline data about the acceptability of differing restorative
      techniques and about the type of intervention that could bring about change in
      pattern of use by community dental officers in two large Trusts in Wales. If a
      postgraduate course in the use of stainless steel crowns is to meet dental
      officers' needs, it should address their concerns about the use of crowns.

PMID- 11310099
TI  - Detection of dentine caries using the oblique lateral radiograph.
AB  - OBJECTIVES: The aim of the study was to evaluate the level of agreement between
      bitewing radiographs and oblique lateral radiographs for the diagnosis of dental
      caries extending into dentine, and to draw conclusions from the results as to
      which view is more useful. SAMPLE: Radiographs were selected from patients
      attending an orthodontic assessment clinic: 53 patients, 52% male, 48% female,
      aged 6-18 years old. Total 105 bitewings and 105 oblique lateral radiographs.
      METHODS: Contemporaneous bitewing and oblique radiographs taken over the period
      1987-97 were independently assessed by two dentists for the presence of caries
      extending into dentine. RESULTS: The agreement between the oblique lateral and
      the bitewing radiographs for the presence of approximal caries expressed in the
      form of Cohen's Kappa gave values of 0.64 for observer 1 and 0.53 for observer 2.
      For occlusal caries, values were 0.72 for observer 1 and 0.56 for observer 2.
      Kappa values for the level of agreement between observers and for the same
      observer on different occasions were within the range 0.5-0.95 for both types of
      film. CONCLUSION: The Kappa values for the agreement between the two views as
      well as the intra- and inter-observer agreement and reproducibility of the
      oblique lateral view all fall in the range K = 0.5-0.75. Results suggested a fair
      to good agreement in diagnoses made using the two types of film. However, levels
      were lower than estimates of reproducibility reported for bitewing films alone.

PMID- 11310100
TI  - Aspiration of an avulsed primary incisor. A case report.
AB  - A 7-year-old girl had injured her maxillary primary incisors in a playground. One
      of the already-mobile incisors had been avulsed. The child who had a cough and
      breathing difficulties during sleep was diagnosed as suffering from upper
      respiratory infection and was treated with antibiotics. A few days later because
      her body temperature was elevated a chest radiograph was taken. The radiograph
      revealed an aspirated tooth in her right bronchus with atelectasis of the lower
      lobe. The tooth was removed by bronchoscopy. Dentists should suspect any tooth
      that has been avulsed and not found as possibly aspirated.

PMID- 11310101
TI  - Primary failure of eruption in the permanent dentition of siblings.
AB  - Primary failure of eruption is a condition where there is eruption failure in the
      permanent dentition with no obvious mechanical cause. It has previously been
      reported in the literature as a cause of posterior openbite, with a varying
      degree of familial inheritance. This case report describes two sisters that
      experienced eruption failure in the permanent dentition, most notably of the
      first and second molars, with greater severity in the younger sister. Teeth were
      exposed in both patients and orthodontic traction was applied with little or no
      success. The report provides further evidence of the genetic contribution to the
      aetiology of this condition and also highlights the problems in attempting
      treatment, including exposing to the oral environment teeth that are infra
      occluded and difficult to clean effectively.

PMID- 11310102
TI  - The dental management of a child with LEOPARD syndrome.
AB  - This report describes the dental management of a child with LEOPARD syndrome who
      presented with multiple grossly carious primary teeth. Comprehensive dental care
      was carried out under general anaesthesia.

PMID- 11310103
TI  - Rare benign tumours of oral cavity--capillary haemangioma of palatal mucosa: a
      case report.
AB  - Haemangiomas are benign tumours composed of blood vessels, they are probably
      developmental rather than neoplastic in origin. Haemangiomas are often present at
      birth but may become more apparent during life. The tumours appear as a flat or
      raised reddish-blue lesions and are generally solitary. They are occasionally
      seen on the palatal mucosa. Haemangiomas are classified on the basis of their
      histological appearance as capillary, mixed, cavernous or a sclerosing variety
      that tends to undergo fibrosis. Their differential clinical diagnosis is based on
      appearance. The tumours may be slowly progressive, involving extensive portions
      of the superficial and deep blood vessels. Function may be affected where
      development of the lesion is extra-invasive. Colour change on pressure is a
      common finding with return to the original colour on withdrawal of pressure. The
      case presented here was referred because of swelling and recurrent periodontal
      bleeding. The lesion was diagnosed as a capillary haemangioma through
      histopathology. Although different therapeutic procedures have been reported, in
      this case surgical excision was carried out under general anaesthesia following
      hospitalization. Despite their benign origins and behaviour, haemangiomas in the
      region of oral cavity are always of clinical importance to the dental profession
      and require appropriate clinical management. Dental practitioners and oral
      surgeons need to be aware of these lesions because they may pose serious bleeding
      risks.

PMID- 11310104
TI  - Diagnosis of occlusal caries in primary teeth.
AB  - Much research has been published over the last few years looking at alternative
      diagnostic systems for the diagnosis of occlusal caries in permanent teeth, but
      there has been little research on primary teeth. The aim of this study was to
      compare the accuracy of one alternative system (the Electronic Caries Monitor
      [ECM]) against visual diagnosis for the detection of occlusal dentine caries in
      primary teeth. Fifty-eight apparently noncavitated extracted first and second
      primary molars were selected. They were examined visually and with the ECM for
      dentine caries. Presence or absence of caries was validated by hemisecting the
      teeth and examining them under a stereomicroscope--37 teeth had occlusal dentine
      caries, 21 were sound or had enamel caries. Sensitivities and specificities of
      the ECM diagnoses were 0.81 and 0.90, respectively, and for the visual diagnosis
      were 0.73 and 1. In conclusion, the ECM did not provide increased accuracy over
      visual diagnosis when detecting occlusal caries in primary teeth.

PMID- 11310105
TI  - British Society of Paediatric Dentistry: a policy document on fissure sealants in
      paediatric dentistry.

PMID- 11310106
TI  - Outside the academic door.

PMID- 11310107
TI  - Fluoride pit and fissure sealants: a review.
AB  - There are two methods of fluoride incorporation into fissure sealants. In the
      first method, fluoride is added to the unpolymerized resin in the form of a
      soluble fluoride salt that releases fluoride ions by dissolution, following
      sealant application. In the second method, an organic fluoride compound is
      chemically bound to the resin and the fluoride is released by exchange with other
      ions (anion exchange system). This report reviews the literature on the
      effectiveness of all the fluoride-releasing sealants--commercial and experimental
      -that have been prepared using either the former or the latter method of fluoride
      incorporation. There is evidence for equal retention rates to conventional
      sealants and for ex vivo fluoride release and reduced enamel demineralization.
      However, further research is necessary to ensure the clinical longevity of
      fluoride sealant retention and to establish the objective of greater caries
      inhibition through the fluoride released in saliva and enamel.

PMID- 11310108
TI  - Interceptive orthodontics in the real world of community dentistry.
AB  - OBJECTIVE: To test the applicability and effectiveness of interceptive
      orthodontics in a community field trial. DESIGN: Prospective screening for
      suitable malocclusions, implementation of treatment and analysis of outcomes 12
      months later. SETTING: Community dentistry in urban and rural areas of Northern
      Ireland, 1996-98. SUBJECTS AND METHODS: The initial sample consisted of 2002
      children (1014 boys, 988 girls) who were screened in routine community dental
      inspections. One thousand and sixty (523 aged 9 years, 537 aged 11 years) were
      domiciled in the urban area of greater Belfast and 942 (479 aged 9 years, 463
      aged 11 years) in the rural area of Enniskillen and Omagh, Co. Tyrone.
      INTERVENTIONS: Interceptive orthodontic treatment. OUTCOME MEASURES: Dental
      health component of the Index of Orthodontic Treatment Need (IOTN) and specially
      devised local indices of treatment outcomes. RESULTS: With the use of an
      interception gauge, orthodontic screening was included in the community dental
      inspections without difficulty. Thirty-three per cent of children were in need of
      interceptive treatment. Only 20% of those in need both attended for recall and
      underwent treatment. Compliance was better in the rural area but the need, with
      particular reference to extraction of carious first molars, was greater in the
      urban area. The numbers of children in IOTN grades 4 and 5 fell from 69% at the
      beginning of the study to 42% at the end. The outcome judged by local indices was
      94% in the range of complete success to minimal improvement with only 2% showing
      deterioration. CONCLUSIONS: One in three children screened in community dental
      inspections at age 9 and 11 years would benefit from interceptive orthodontics.
      Parents and children seem reluctant to accept offers of interceptive orthodontics
      and to having the treatment carried out. Among those complying fully, the
      interceptive measures are very successful. Not only does community interceptive
      orthodontics improve the condition being treated but also reduces the need for
      further treatment.

PMID- 11310109
TI  - Traumatic dental injuries in children.

PMID- 11310110
TI  - A retrospective study of treatment provided in the primary and secondary care
      services for children attending a dental hospital following complicated crown
      fracture in the permanent dentition.
AB  - OBJECTIVES: To investigate treatment provision in primary and secondary dental
      care following complicated crown fracture of permanent teeth. DESIGN AND METHODS:
      Retrospective observational survey of dental records of all patients attending a
      dental hospital trauma clinic during a 2-year period with complicated crown
      fracture. RESULTS: Eighty children (70% male) aged 6-16 years (mean age 10.3
      years) with 98 complicated crown fractures were identified. Of these children,
      54% were seen for emergency treatment on the day of their injury, 75% within 48
      h. Of the 98 injured teeth, 60% were seen initially in general dental practice
      but only 56% of these 59 cases were provided with emergency treatment in
      practice, the others being referred immediately to the trauma clinic for
      treatment. The main cause of fractures was transport, in particular, bicycles.
      Radiographs were available for 96 teeth; for the 43 open apex teeth, the
      definitive treatment was pulp capping (44% of cases) and pulpotomy (30%), with
      vitality maintained in five cases up to 4.8 years after trauma. The 53 closed
      apex cases were treated definitively with pulp capping (38%) and pulpectomy (36%)
      and six teeth had maintained their vitality up to 4.3 years after trauma. Sixty
      seven per cent of the pulp caps and 47% of the 19 pulpotomies provided relied on
      a doubtful coronal seal. This was primarily due to the extensive use of a
      conventional glass ionomer cement as an emergency bandage. The use of an etched
      or bonded material at initial presentation extended the Median Survival Time for
      vitality in open apex teeth from 188 to 377 days and in closed apex teeth from 15
      to 64 days. CONCLUSIONS: Emergency treatment of complicated crown fractures,
      particularly in primary care services is often inappropriate or inadequate with
      regard to emergency management of the exposed pulp and provision of a hermetic
      coronal seal.

PMID- 11310112
TI  - A prospective study of factors affecting survival of replanted permanent incisors
      in children.
AB  - OBJECTIVE: To examine the factors associated with the onset of resorption in
      replanted avulsed permanent incisor teeth and to demonstrate their patterns of
      survival free of resorption. SETTING: Department of Paediatric Dentistry,
      Belfast. DESIGN: Prospective recording of the timing of the injury and of
      replantation, the storage media, the degree of root development and
      contamination, and the completion of root treatment. Clinical and radiographic
      reviews at 3-month intervals. Root resorption classified as replacement and
      inflammatory. Logistic regression and survival curves with freedom from
      resorption as outcomes. RESULTS: In 50 avulsed incisors in children aged 6-16
      years the best predictor of overall resorption was total time of dryness, and
      that for replacement resorption was total extra-oral time. The timing of
      detection of resorption varied from 102 days to 997 days. CONCLUSION: Both total
      extra-oral time and time stored dry are important factors for the onset of
      resorption in replanted avulsed teeth in children.

PMID- 11310111
TI  - Long-term prognosis of crown-fractured permanent incisors. The effect of stage of
      root development and associated luxation injury.
AB  - OBJECTIVES: The aim of the present study was to investigate pulp healing
      responses following crown fracture with and without pulp exposure as well as with
      and without associated luxation injury and in relation to stage of root
      development. PATIENT MATERIAL AND METHODS: The long-term prognosis was examined
      for 455 permanent teeth with crown fractures, 352 (246 with associated luxation
      injury) without pulpal involvement and 103 (69 with associated luxation injury)
      with pulp exposures. Initial treatment for all patients was provided by on-call
      oral surgeons at the emergency service, University Hospital (Rigshospitalet),
      Copenhagen. In fractures without pulpal involvement, dentin was covered by a hard
      setting calcium hydroxide cement (Dycal), marginal enamel acid-etched (phosphoric
      acid gel), then covered with a temporary crown and bridge material. In the case
      of pulp exposure, pulp capping or partial pulpotomy was performed. Thereafter
      treatment was identical to the first group. Patients were then referred to their
      own dentist for resin composite restoration. RESULTS: Patients were monitored for
      normal pulp healing or healing complications for up to 17 years after injury (x =
      2.3 years, range 0.2-17.0 years, SD + 2.7). Pulp healing was registered and
      classified into pulp survival with no radiographic change (PS), pulp canal
      obliteration (PCO) and pulp necrosis (PN). Healing was related to the following
      clinical factors: stage of root development at the time of injury, associated
      damage to the periodontium at time of injury (luxation) and time interval from
      injury until initial treatment. Crown fractures with or without pulp exposure and
      no concomitant luxation injury showed PS in 99%, PCO in 1% and PN in 0%. Crown
      fractures with concomitant luxation showed PS in 70%, PCO in 5% and PN in 25%. An
      associated damage to the periodontal ligament significantly increased the
      likelihood of pulp necrosis from 0% to 28% (P < 0.001) in teeth with only enamel
      and dentin exposure and from 0% to 14% (P < 0.001) in teeth with pulp exposure.
      CONCLUSIONS: In the case of concomitant luxation injuries, the stage of root
      development played an important role in the risk of pulp necrosis after crown
      fracture. However, the primary factor related to pulp healing events after crown
      fracture appears to be compromised pulp circulation due to concomitant luxation
      injuries.

PMID- 11310113
TI  - Utilization of day stay general anaesthesia for the provision of dental treatment
      to children in New South Wales, Australia.
AB  - OBJECTIVES: To assess the demand for paediatric dental general anaesthetic
      services at a specialist paediatric dental unit in Australia and to evaluate the
      changing pattern of general anaesthetic use in children at this unit over the
      past decade. METHODS: A retrospective review of hospital records of a random
      sample of children receiving dental treatment under general anaesthesia during
      the years 1984 and 1996. Demographic and clinical data was collated and analysed
      using SPSS for Windows. RESULTS: The number of children managed under general
      anaesthesia increased from 189 in 1984 to 777 in 1996. This was accompanied by an
      increase in the time the patients waited for treatment. There was little
      difference in the mean age of the patients with over two-thirds of the children
      being under the age of 6 years. Whilst children of Anglo-Saxon origin accounted
      for the majority of patients across the 13-year period there was a significant
      increase in the number of children from Asian or Middle Eastern backgrounds. A
      disproportionate number of these children accessed the services as self
      referrals. Caries remained the most common reason for referral, with trauma and
      dental anomalies accounting for less than 10%. CONCLUSIONS: Despite the general
      decline in dental caries there remain an important group of young children who
      have high treatment needs and for whom general anaesthesia provides a useful
      treatment option. Preventive strategies should be targeted towards these groups
      of children.

PMID- 11310115
TI  - An investigation of language used by children to describe discomfort during
      dental pulp-testing.
AB  - AIM: Studies of the descriptions of pain by children have neglected their
      linguistic development, therefore estimates of dental pain in children may not be
      accurate. This study sought (1) to identify words chosen by children to describe
      dental pain and (2) to establish the effect of linguistic development on that
      description. SAMPLE: Seventy-eight consecutive children between the ages of 5 and
      13 years attending a paediatric dental clinic. METHOD: Each child completed the
      WORD reading comprehension test. They then underwent a pulp test and a simulated
      pulp test, administered by a dentist in a counterbalanced order, of a healthy
      primary canine or permanent incisor, according to the child's age. To describe
      each test, the children had to (1) select words from a list of 58 read by the
      experimenter and (2) give ratings on scales representing 'sore' and 'tingly'.
      RESULTS: Analysis of variance confirmed that the children chose more words for
      the pulp test than for the simulated test (P < 0.001); the former also elicited
      higher ratings for 'sore' and 'tingly'. The numbers of words chosen were
      transformed by a square root constant to ensure a normal distribution. Multiple
      regression analysis then showed that (1) the better the children's reading
      comprehension, the fewer words they chose, possibly because they were less
      inclined to choose unfamiliar words, and (2) the older they were, the more words
      they chose, possibly because of having more experience of pain. There were
      similar findings for ratings of 'sore' and 'tingly'. CONCLUSIONS: To assess
      children's experience of pain (1) they need to be presented with a list of words
      like the ones in this study, (2) the numbers of words chosen by them would
      represent the severity of pain, and (3) those numbers need to be adjusted for the
      children's reading comprehension and age.

PMID- 11310114
TI  - The effect of wavelength, bandwidth, and probe design and position on assessing
      the vitality of anterior teeth with laser Doppler flowmetry.
AB  - OBJECTIVES: To investigate the effect of four variables: wavelength (633 nm and
      780 nm), bandwidth filter (3 kHz, 15 kHz, 22 kHz), probe fibre separation (250
      microns) and 500 microns) and distance of the probe from the gingival margin (2-3
      mm and 4-5 mm) when assessing the vitality of anterior teeth with a laser Doppler
      flowmetry system. DESIGN: Split-mouth cohort clinical trial. SETTING: Childrens
      dental clinic, Glasgow Dental Hospital and School. SAMPLE AND METHODS: Sample
      included 11 non-vital maxillary incisors with necrotic pulps in 10 patients (mean
      age 12.25 years old). Recordings were taken from the non-vital tooth and from a
      vital maxillary incisor from the same patient, using all 24 combinations of the
      recording variables listed above. The vital/non-vital ratios of the signals from
      the 11 pairs of teeth were calculated and discriminant analysis applied to the
      data. RESULTS: Of the variables investigated, the combination of a 633 nm laser
      source with a 3 kHz bandwidth filter using a probe with a 500 microns fibre
      separation placed 2-3 mm from the gingival margin was the most reliable, with 10
      out of a possible 11 true positives for pulpal necrosis, no false positives, and
      one equivocal diagnosis, and was the only combination that recorded a smaller
      blood flow from the non-vital tooth compared with the vital control tooth for all
      11 pairs of teeth investigated. CONCLUSIONS: It was concluded, therefore, that
      laser Doppler flowmetry can be of use in assessing the vitality of anterior teeth
      and that this is the preferred combination of recording variables for further
      investigations.

PMID- 11310116
TI  - Conservative approach in the management of mandibular fractures in the early
      dentition phase. A case report and review of the literature.
AB  - A case is described of the management of bilateral fractures of mandible as a
      result of being kicked by a horse, in a 2-year-old child. The fractures were
      treated without any surgical intervention and the child made a good recovery with
      good function and appearance. The fractured mandible in children under the age of
      5 years provides us with difficult treatment options. By encompassing the
      anatomical and developmental potential of facial tissues, both hard and soft, the
      majority of these cases can be managed conservatively. This negates the
      disadvantages of attempting potentially growth disturbing interventional surgery.

PMID- 11310117
TI  - Degloving injury to mental protuberance: a case report.
AB  - Sporting injuries are increasing in frequency with the increase in leisure time.
      This report describes a case of degloving of the mental protuberance. Ideally
      this injury should be treated as soon as possible by repositioning the displaced
      tissue and closure. Immediate assistance was not sought until superimposed
      infection caused pain and swelling. Because the wound was infected, treatment was
      aimed at obtaining healing by secondary intention.

PMID- 11310118
TI  - Orbital infection arising from a primary tooth: a case report.
AB  - Odontogenic infections may spread to the orbit by one or more of several paths.
      Such extension is potentially dangerous and may lead to loss of vision. A case of
      infection from a primary tooth, which extended to the retrobulbar area is
      presented in this report. Treatment included surgical drainage of the resulting
      subperiosteal orbital abscess through a Caldwell-Luc approach as well as
      aggressive antibiotic therapy. The importance of early suspicion of this entity
      and its potential sequelae are discussed.

PMID- 11310119
TI  - Garre's osteomyelitis of an unusual origin in a 8-year-old child. A case report.
AB  - Garre's osteomyelitis is a type of chronic osteomyelitis that primarily affects
      children and adolescents. Although the disease is well described in the dental
      literature and is usually associated with an odontogenic infection resulting from
      caries, a number of other causative factors have been occasionally reported, such
      as a dental extraction or a mild periodontitis. There have also been cases of
      unknown aetiology. This paper describes a case of Garre's osteomyelitis in an 8
      year-old child, in whom the condition arose following a local periodontal
      infection in an ectopically erupting first permanent molar that was in
      infraocclusion. The lesion remained unresolved for a period of over 6 months as a
      result of misdiagnosis, following a number of unsuccessful treatment attempts.
      Identification of the true cause and treatment through periodontal surgery
      resulted in lesion resolution and resolved the diagnostic problem. Dentists
      should be aware that the periodontium may be a potential source of infection for
      Garre's osteomyelitis in children, particularly in the presence of ectopically
      erupting posterior teeth. In such cases, periodontal treatment should be
      sufficient to treat the disease and extraction of the tooth involved may not be
      necessary.

PMID- 11310120
TI  - UK National Clinical Guidelines in Paediatric Dentistry. The pulp treatment of
      the primary dentition.

PMID- 11310121
TI  - A preliminary investigation of dental disease in children with HIV infection.
AB  - OBJECTIVE: To establish the levels of dental caries and gingivitis in a group of
      HIV-positive children. STUDY GROUP: The study group comprised 35 children with
      the Human Immunodeficiency Virus attending The Great Ormond Street Hospital For
      Children. OUTCOME MEASURES: Outcome measures included the number of decayed,
      missing and filled teeth and surfaces in both the primary and permanent
      dentitions; plaque and gingivitis scores. RESULTS: The children included 18 boys
      and 17 girls. They were aged from 6 months to 18 years, with 17 aged 5 years or
      less and 15 aged 6 years or older. Twenty-four of the 35 children had some caries
      experience. The mean DMFT was 4.4 and for those with permanent teeth the mean
      DMFT was 0.7. Mean plaque and gingivitis scores were 16.7 and 5.1 for plaque and
      gingivitis adjacent to primary teeth and 8.0 and 5.7 for that related to
      permanent teeth. CONCLUSIONS: There is a significant treatment need for children
      with HIV.

PMID- 11310122
TI  - Dental caries prevalence and dental health behaviour in HIV infected children.
AB  - OBJECTIVES: To determine dental caries prevalence in a group of HIV positive
      children and their reported dental health behaviour. DESIGN: Standardized
      epidemiological dental examination and structured interview. SETTING: Paediatric
      HIV outpatient department in a South London hospital. STUDY POPULATION: HIV
      positive children attending the above outpatient clinic over a 6-month period (30
      subjects) and parents (20 informants). METHODS: Epidemiological examination of
      children was undertaken by one trained and calibrated examiner to determine
      caries prevalence using dmft/DMFT. Parents were interviewed to obtain information
      on their children's dental health behaviour: toothbrushing, diet, fluoride; oral
      medication and dental attendance were explored. RESULTS: Sixty-three per cent (n
      = 19) of children had dental caries experience, much of it untreated. Mean
      dmft/DMFT was 4.4. Sixty per cent (n = 18) of all children presented with active
      or untreated caries and the care index for those at/under age 5 years was low
      (10%). Unfavourable dental health behaviour included: consumption of nonmilk
      extrinsic sugars at night, use of sugar-based medications, low fluoride intake,
      late commencement of toothbrushing and poor dental attendance. Dental health was
      not considered a priority for many of these children. Parents did not necessarily
      disclose their child's HIV status on dental attendance. CONCLUSION: Caries
      prevalence was high, much of the disease untreated, and unfavourable dental
      health behaviour, including the use of sugar-based medicines was common. HIV
      infected children should be considered a high caries risk and receive appropriate
      dental care, in terms of both treatment and preventive services, following
      confirmation of seropositivity.

PMID- 11310123
TI  - Denture satisfaction and clinical performance in a paediatric population.
AB  - OBJECTIVES: The objectives of this study were to investigate the clinical
      performance of partial upper dentures in children and to assess reported denture
      satisfaction in this young population. DESIGN: This was a retrospective study
      using patients' dental records in conjunction with a postal questionnaire.
      SETTING: The Paediatric Dentistry Clinic, School of Clinical Dentistry,
      Sheffield. SAMPLE AND METHODS: Fifty-eight children (aged 7-17 years) who had
      been provided with a partial upper denture to replace one or more missing
      permanent incisors were included in the study. The patients' dental records were
      examined for the following details: tooth type missing, presence of retained
      incisor roots, aetiology of tooth absence, age at which the denture was first
      provided, total time period dentures had been worn, and frequency and type of any
      denture repairs or replacements. Next a short questionnaire was sent to each
      child, which sought an evaluation of several parameters of denture satisfaction
      including: overall attitude towards wearing a denture, denture appearance, ease
      of eating, comfort and perceived degree of teasing from peers. Visual analogue
      scales (VAS) were employed to provide a graded response. RESULTS: 70.7% of
      subjects had a single missing incisor and trauma was the most common cause of
      tooth loss (77.3%). The mean age at which patients started wearing a denture was
      11.6 years and the mean length of time dentures had been worn, at the time of the
      investigation, was 2.1 years. A 'T-shaped' denture was most commonly employed
      (77.5% of dentures). Overall, 36.2% of subjects had required at least one denture
      repair, 28.2% presenting within a year of denture provision. One or more denture
      replacements had been received by 60.3% of the patients, and 43.6% had required
      this within a year. Component failure was highest for the denture tooth (40% of
      repairs) and a change in the patient's dentition necessitated a denture remake in
      66% of cases. VAS scores for parameters of denture satisfaction indicated an
      overall positive evaluation of the dentures, with the most positive response
      relating to ease of eating. However, the reported degree of teasing was high and
      increased with time. The only significant difference for denture satisfaction
      according to gender was for mastication: girls reportedly found eating easier
      than did boys. CONCLUSION: Children are generally accepting of upper partial
      dentures, but their poor clinical performance is of concern and there is need for
      improvement.

PMID- 11310124
TI  - Oral manifestations and dental status in paediatric HIV infection.
AB  - OBJECTIVE: To describe the incidence and prevalence of oral manifestations of HIV
      infection in a population of perinatally infected children. DESIGN: Retrospective
      and prospective study of a cohort of perinatally HIV-infected children. SETTING:
      Community hospital and community-based paediatric clinic. SAMPLE AND METHODS:
      Forty perinatally HIV-infected children with a median age of 12 months were
      eligible and selected for the study, which included a medical chart review from
      birth and prospective follow-up. Each child was examined quarterly for oral
      manifestations, tooth eruption, and for 27 children, caries and periodontal
      status. RESULTS: The incidence of pseudomembranous candidiasis was 43% (95% CI,
      27-58%) within 6 months of birth. Oral candidiasis (defined as pseudomembranous
      or erythematous) was positively associated with low CD4 counts and the occurrence
      of plaque. Children with low CD4 counts were also found to have fewer teeth than
      children with high CD4 counts, after adjusting for age. CONCLUSIONS: Oral
      manifestations are common in paediatric HIV infection and are possible predictors
      of HIV disease progression. Primary care of HIV-infected children should include
      periodic oral examinations to monitor their HIV disease progression and to
      alleviate symptoms associated with oral opportunistic infections.

PMID- 11310125
TI  - Oral health survey of 5-12-year-old children of National Guard employees in
      Riyadh, Saudi Arabia.
AB  - OBJECTIVES: To assess the oral health status, preventive practices and mutans
      streptococci (MS) levels among the children of National Guard personnel living in
      Riyadh, Saudi Arabia. DESIGN: Cross-sectional study of schoolchildren. SETTING:
      Dental Clinic of the National Guard Hospital in Riyadh, Saudi Arabia. SAMPLE AND
      METHODS: A sample of 272 5-12-year-old children, 154 males and 118 females (95%
      Bedouin), were selected from approximately 35 National Guard schools in the
      Riyadh area. An examination was performed in the dental clinic in the National
      Guard hospital. Oral hygiene was assessed using the Simplified Debris Index (DI
      S); Gingival Index (GI) was used to measure gingival health; dental fluorosis was
      recorded according to the criteria of Dean. Dental caries (dmft, dmfs, DMFT and
      DMFS) was recorded according to the recommendations of Haugejorden. Concentration
      of MS in saline rinse samples was assessed by routine laboratory methods and
      expressed as colony forming units (CFU) per ml (log10). RESULTS: There was a high
      level of dental caries (mean dmft = 3.8 +/- 3.2; mean dmfs = 21.5 +/- 15.7; mean
      DMFT = 2.0 +/- 1.9; mean DMFS = 3.1 +/- 3.7). Only 0.7% of the children had no
      caries experience (dmft + DMFT). MS levels ranged from 0 to 7.5 x 10(5) CFU per
      ml (mean MS = 4.10 +/- 0.90 log10 CFU per ml). A significant relationship between
      MS and caries experience was observed (P = 0.003). Mild fluorosis was observed in
      14% of the children. Oral hygiene scores indicated that most of the examined
      tooth surfaces had detectable plaque (mean DI-S = 1.78). Gingivitis was present
      in 100% of the children and was considered moderate to severe in 14% (mean GI =
      1.18). CONCLUSIONS: The study revealed a high level of oral diseases and poor
      oral hygiene in the study population and a need for therapeutic and preventive
      measures.

PMID- 11310128
TI  - Multiple dental anomalies in a young patient: a case report.
AB  - This case illustrates the management of multiple dental anomalies in a young
      patient, which included anomalies of number and morphology. Although individually
      these anomalies are not uncommon, the combination is unusual and highlights the
      importance of careful clinical and radiographic examination of patients with
      dental anomalies.

PMID- 11310126
TI  - The relationships between dietary guidelines, sugar intake and caries in primary
      teeth in low income Brazilian 3-year-olds: a longitudinal study.
AB  - OBJECTIVES: To investigate the effects of dietary guidelines on sugar and sugar
      intake at day nurseries, and other potential risk factors on dental caries in two
      groups of low socio-economic nursery schoolchildren. DESIGN: Nursery based,
      longitudinal study. SETTING: Metropolitan area of Recife, north-eastern Brazil.
      SAMPLE AND METHODS: The study population comprised 510, 3-year-old low socio
      economic nursery schoolchildren. Sugar intake at the nursery was based upon a
      weighed inventory method during 2 non-consecutive days. Parents answered a
      questionnaire. RESULTS: Children attending nurseries not adopting guidelines on
      reduction of sugar intake had a higher caries risk, with an odds ratio of 3.6
      compared to those attending nurseries with guidelines. A higher caries increment
      was related to higher daily frequency and weight of sugar intake at nursery,
      overall daily frequency of sugar intake (sugar intake at home plus nursery), past
      caries experience, use of fluoride, and habits related to toothbrushing. Children
      having more than 32.6 g of sugar daily at nursery were 2.99 times more likely to
      have high caries increment than those having less than that amount. CONCLUSIONS:
      Sugar intake at nursery and the adoption of guidelines on sugar were associated
      with lower caries increment in low income nursery schoolchildren. A number of
      modifiable factors such as a higher daily frequency and weight of sugar intake at
      nursery, use of fluoride and habits related to toothbrushing were strongly
      related to caries increment.

PMID- 11310127
TI  - Relationship between premature loss of primary teeth and the development of
      temporomandibular disorders in children.
AB  - AIM: This study evaluated the prevalence of signs of temporomandibular disorders
      (TMD) in children with and without premature loss of primary teeth. SAMPLE: Fifty
      eight children, aged 4-6 years, with missing primary molars, were compared with
      58 age- and sex-matched control children with complete primary dentitions.
      METHOD: All the children underwent an examination that consisted of palpation and
      assessment of the joints and associated muscles for tenderness and joint sounds.
      Maximum vertical opening and deviation during jaw opening were also recorded.
      Children with any single anomalous finding were designated positive for TMD
      signs. RESULTS: There were no statistically significant differences in the
      prevalence of single or collective TMD signs between the two groups. CONCLUSION:
      The results of this study show that premature loss of primary teeth,
      uncomplicated by other factors, does not appear to be an aetiological factor for
      TMD development.

PMID- 11310129
TI  - Oral myiasis: a case report.
AB  - Oral myiasis is a rare condition caused by the invasion of tissues by larvae of
      flies. A case of gingival myiasis is presented in a 12-year-old boy with learning
      disability. The patient was unaware of the lesion, although it produced a
      swelling partially covering the teeth. The lesion was treated with ether, which
      forced the larvae out, and irrigated with warm saline solution. Follow-up
      examination revealed complete subsidence and healing of the lesion.

PMID- 11310130
TI  - Individualized mouth prop for dental professionals and carers.
AB  - Maintaining a high standard of dental health in children with special needs,
      particularly those who are unable to control mandibular activity, can prove
      difficult and time consuming for parents, carers and dental professionals. This
      article describes the construction of an individually made and relatively
      unobtrusive finger guard mouth prop, designed to facilitate intraoral examination
      and oral hygiene care for these children. An initial evaluation by a number of
      users found these mouth props were simple to fit, stable and provided adequate
      finger protection. All users planned to continue using their mouth prop after the
      trial period. It is concluded that similar finger mounted mouth props may help
      facilitate dental care and oral hygiene for children requiring special care.

PMID- 11310131
TI  - UK National Clinical Guidelines in Paediatric Dentistry. Management of the
      stained fissure in the first permanent molar.

PMID- 11310132
TI  - Dental attendance and dental health behaviour in children from deprived and non
      deprived areas of Salford, north-west England.
AB  - AIMS: Firstly, to investigate reported oral health behaviours and changes in
      behaviour of 3-year-old children in deprived and non-deprived wards of Salford,
      UK. Secondly, to examine differences in this behaviour between symptomatic and
      non-symptomatic attenders. Thirdly, to note sources of dental health advice given
      to parents. DESIGN: Interviews using structured questionnaires. SETTING: Play
      groups and nurseries in Salford, North-West England. METHOD: Interviews with
      representative groups of mothers of 3-year-old children attending play groups and
      nurseries in selected deprived and non-deprived wards, enquiring about dental
      attendance, dental health behaviour and changes in these resulting from dental
      advice. RESULTS: Mothers of 284 children were interviewed. Over three-quarters of
      the children were reported to have a drink or food at bed-time, or during the
      night, often containing non-milk extrinsic sugars (NMES); more in the deprived
      wards. All parents reported a tooth brushing habit with over 90% using a fluoride
      toothpaste, those in non-deprived wards beginning earlier in life and brushing
      more frequently. Most parents claimed that their children had seen a dentist at
      some time; more in the non-deprived wards. More children in deprived wards were
      symptomatic attenders sometimes experiencing extractions under general
      anaesthesia. More parents in deprived wards remembered receiving dental health
      advice from the dental team and were more inclined to act on that advice.
      CONCLUSION: Children from deprived wards were reported to have different dental
      health habits from those from non-deprived wards. They were more likely to be fed
      NMES in food and drinks at bedtime, begin brushing later in life and brush less
      frequently and attend the dentist symptomatically. Their parents claimed to have
      received more dental health advice from the dental team and were more likely to
      act on that advice.

PMID- 11310133
TI  - Dental treatment under general anaesthesia at a hospital in Jeddah, Saudi Arabia.
AB  - Dental General Anaesthesia (DGA) has been shown to be of value in providing both
      restorative treatment and extractions in children who are unable to accept this
      using other methods of management. AIMS: The aims of this retrospective study
      were to determine the characteristics of patients attending for treatment under
      DGA at a centre in Saudi Arabia, to describe the type of dental treatment carried
      out using DGA and in the subsequent 3-year period. SAMPLE AND METHOD: Data were
      collected from hospital records of 555 patients who received treatment under DGA
      at King Fahad Hospital in Jeddah, Saudi Arabia, between 1995 and 1997. RESULTS:
      Ninety three percent of the patients were aged 8 or younger at the time of DGA,
      with 43% being under 5 years of age. The main indications for use of DGA in the
      youngest age group were dental management of rampant caries (77% of the youngest
      age group) and inability to accept treatment under local anaesthesia (49% of
      those aged 5-8 years). Seventy percent of patients had treatment involving both
      extractions and restorative care, and the majority, 81%, had one tooth or more
      restored with preformed metal crowns. Sixty-three percent of patients attended
      for recall after 6 months but only 10% did so after a 3-year interval. Only one
      of the 555 patients received a second DGA at the same centre during the 3 years
      following treatment. CONCLUSIONS: The service studied provides dental treatment
      primarily for children with extensive disease. Failure to attend for recall was
      common, suggesting that preventive methods which rely on regular attendance may
      not be successful in this group of children.

PMID- 11310134
TI  - Effectiveness of a caries preventive program in pregnant women and new mothers on
      their offspring.
AB  - OBJECTIVE: The medical centre at Almirante Nef Naval Hospital, Vina del Mar,
      Chile, operates a mother and child preventive dental program (PDP) which includes
      women from their fourth month of pregnancy and mothers with their offspring. The
      aim was to evaluate the effectiveness of this prenatal and postnatal prevention
      program after the first four years. METHODS: The prevalence of early childhood
      caries of 180 1- to 3.5-year-old children enrolled in the PDP was compared with
      180 non-participating children. The control group was randomly selected from the
      rolls of the healthy child system of of the Valparaiso-San Antonio Health Service
      and was comparable by age, socio-economic status and level of fluoride in the
      drinking water (1.0 p.p.m. F) with the PDP group. Clinical caries examinations
      were conducted by two calibrated examiners using the WHO visual criteria.
      RESULTS: In the PDP group, 97% of the children were caries free compared with the
      77% in the control group. The dft (mean +/- SD) of the PDP children was 0.11 +/-
      0.78 versus 0.66 +/- 1.55 for the control children, a difference of 83.3%. The
      differences between the groups in caries-free status and caries prevalence were
      both statistically significant (P < 0.05). CONCLUSIONS: The preventive dental
      program was effective in inhibiting caries in pre-school children, even in a
      population already receiving the benefits of community water fluoridation.

PMID- 11310135
TI  - The relationship between sweetness preference, levels of salivary mutans
      streptococci and caries experience in Brazilian pre-school children.
AB  - AIM: To analyse the relationship between preference for sweetness, levels of
      salivary mutans streptococci and levels of caries in low socio-economic 4-5-year
      old Brazilian children. DESIGN: A cross-sectional survey. SUBJECTS AND METHODS:
      298 children of both sexes, who, in 1998, were regularly attending public
      nurseries were randomly selected. Caries experience was assessed according to WHO
      guidelines. Saliva samples were analysed for mutans streptococci using the
      spatula method. Children's preference for sugar was measured using the 'Sweet
      Preference Inventory'. Personal interviews with the mothers were conducted.
      RESULTS: 255 children completed all aspects of the research, a response rate of
      85.6%. 34.9% of them were caries-free. The mean dmf-s was 4.25 (SD 6.16), the
      decayed component being 3.56 (SD 5.82) and the filled surfaces, 0.69 (SD 1.85).
      For these pre-school children; male sex (P < 0.01), single parent (P < 0.01),
      habit of eating or drinking items that contained non-milk extrinsic sugar between
      meal times (P < 0.05) and high levels of salivary mutans streptococci (P < 0.001)
      were significantly associated with higher dmfs scores. There was no statistical
      relationship between sweetness preference and dental caries and with mutans
      streptococci levels. CONCLUSION: Levels of salivary mutans streptococci but not
      sweetness preference were potential good predictors of caries experience among 4
      5 year-old-children living in urban area of Brazil.

PMID- 11310137
TI  - Nasopalatine duct cyst: a case report.
AB  - A case of a nasopalatine duct cyst is reported in an 8-year-old. The clinical
      presentation was of intermittent palatal swelling and the diagnosis was confirmed
      with radiological and histological examination. This type of cyst is rare in
      children and should not be excluded from a differential diagnosis in younger age
      groups.

PMID- 11310136
TI  - The KBG syndrome, characteristic dental findings: a case report.
AB  - Short stature and developmental delay may be observed in many genetic conditions
      and well-defined syndromes. A 7-year-old girl presented with the non-specific
      findings of subtle dysmorphism, short stature and developmental delay. Although a
      genetic syndrome was suspected, a definitive diagnosis was not made until the
      dental findings of KBG syndrome were recognised, namely grossly enlarged
      maxillary permanent central incisors and hypodontia.

PMID- 11310138
TI  - The dentofacial manifestations of XXXXY syndrome: a case report.
AB  - This paper presents a six-year-old patient with XXXXY syndrome, whose oral
      findings included a cleft soft palate, hyper- or meso-taurodontism in eight
      primary molars and in the mandibular permanent first molars, five congenitally
      missing premolars, and delayed development of the permanent tooth germs. The
      maxillary and mandibular primary central incisors were in a cross-bite
      relationship. Cephalometric findings showed a short ramus of the mandible and a
      short maxilla in the anterioposterior plane. The anteroposterior jaw relationship
      was in harmony. The cross-bite was considered to be due to the retroinclination
      of the maxillary primary incisors. This case emphasises the importance of regular
      dental care, and monitoring of facial growth and dental development in children
      with XXXXY syndrome.

PMID- 11310139
TI  - Description of a clinical technique for tooth extraction in the cleft lip and
      palate area.
AB  - Cleft lip and palate are relatively common congenital malformations, which may
      require specialist paedodontic treatment. In this article, the case of a 9-year
      old boy with bilateral complete cleft lip and palate is presented. He attended
      the Hospital for Rehabilitation of Craniofacial Anomalies (HRAC) for routine
      examination, during which the presence of pre-canine supernumeraries bilaterally
      in the cleft area was seen. The extraction of these dental elements was justified
      by extensive carious lesions and because they represented a potential problem
      during secondary palatoplasty. The precautions needed in tooth extraction in
      patients with cleft lip and palate are described, together with illustrations of
      the clinical procedure.

PMID- 11310140
TI  - A study of risk factors associated with nursing caries in Taiwanese children aged
      24-48 months.

PMID- 11310142
TI  - Teaching and learning: time to change.

PMID- 11310144
TI  - Eruption disturbances of mandibular permanent canines in Japanese children.
AB  - OBJECTIVES: The purpose of this study was to clarify the cause and prognosis of
      eruption disturbance of mandibular permanent canines. SAMPLE AND METHODS: Fifteen
      Japanese children who visited Niigata University Dental Hospital between 1979 and
      1997 with unerupted and/or impacted mandibular permanent canines were examined.
      RESULTS: All cases showed unilateral disturbances. The eruption disturbance of 6
      mandibular canines was associated with a calcified obstacle such as an odontoma
      (5 cases) or a supernumerary tooth (1 case). After removal of the obstacle, 5
      canines were aligned within the dentition. Out of 10 cases, where the permanent
      canine germ showed malpositioning or aberrant eruption path, 5 primary
      predecessors had undergone endodontic treatment. In these 10 cases, 6 canines
      erupted after treatment, two were extracted and the remaining two were left in
      their impacted position. CONCLUSIONS: The present results suggest that it is
      relatively easy for the position of unerupted mandibular canines associated with
      calcified obstacles to be improved by removal of the obstacle, but that it is
      more difficult for teeth showing anomaly in the position of the canine germ to be
      aligned within the dentition.

PMID- 11310143
TI  - Dens invaginatus: a retrospective study of prophylactic invagination treatment.
AB  - AIM: To evaluate the prognosis for pulp survival in teeth with dens invaginatus
      (DI) subjected to prophylactic invagination treatment. DESIGN: A retrospective
      study by examination of dental records and radiographs. SAMPLE AND METHODS: The
      dental records of all patients referred to the Eastman Dental Institute,
      Stockholm, Sweden, with the diagnosis dens invaginatus between the years 1969
      1997 were reviewed. Clinical data was collected from the dental records and the
      diagnosis DI was confirmed on the radiographs from the time of referral. 95 teeth
      in 66 patients had been subjected to prophylactic invagination treatment. The
      retrospective evaluation was based on an examination of the radiographs available
      from the follow-ups. RESULTS: 11.3% of the teeth that were followed for 6 months
      or longer (n = 80) were judged as failures, All failures were initially
      classified as Oehlers type 2. CONCLUSION: The findings stress the importance of a
      follow-up program for teeth subjected to prophylactic invagination treatment in
      order to avoid serious periradicular complications that could influence the
      outcome of the endodontic treatment.

PMID- 11310145
TI  - [Screening strategies for vulvar preneoplastic and neoplastic lesions].
AB  - BACKGROUND: Although they cover superficial areas, preneoplastic and neoplastic
      lesions of the vulva are often diagnosed late. The reasons for this delay is the
      low incidence of this invasive neoplasm, the advanced age of patients, the non
      specific symptoms mainly taking the form of itch, burning, dyspareunia and blood
      loss, which are also compatible with a non-neoplastic infective pathology. The
      late diagnosis of carcinoma of the vulva may also be linked to the inadequate
      examination of the external genitals by doctors as a result of insufficient
      specific knowledge. Epidemiological data and the natural history of VIN lesions
      and carcinoma of the vulva argue that mass screening is not feasible, but an
      adequate programme of early diagnosis must be introduced. Early diagnosis is
      linked to three key elements: targeted anamnesis, clinical examination and the
      appropriate use of the various diagnostic procedures. Vulvoscopy represents the
      most reliable method, above all because it allows a biopsy to be taken of any
      suspected lesion. METHODS: From January 1992 to December 1998, a total of 1678
      vulvoscopies were performed at the Institute of Clinical Obstetrics and
      Gynecology of the University of Catania in patients aged between 16 and 82 years
      old. Biopsies were taken of all suspected lesions. RESULTS: Sixty-nine cases of
      VIN (4.11%) were diagnosed: 28 VIN1, 24 VIN2 and 17 VIN3. Lesions were only
      symptomatic in 39.1% of cases. CONCLUSIONS: The association of vulvoscopy with
      biopsy of suspected lesions, even in the absence of vulvar symptoms, represents
      the most efficacious method for the diagnosis of intraepithelial lesions.

PMID- 11310141
TI  - British Society of Paediatric Dentistry: a policy document on management of
      caries in the primary dentition.

PMID- 11310146
TI  - [Cure of female sterility. Treatment of hydrosalpinx].
AB  - BACKGROUND: The aim of this study was to show how a laparoscopic salpingectomy
      can positively modify infertile patients pregnancy rate after a diagnosis of
      hydrosalpinx, obtaining, through successive assisted procreation programs, a
      pregnancy rate equal to the pregnancy rate obtained in good conditions. METHODS:
      A group of 19 women under infertility treatment was evaluated: of these women, 11
      were included less than three times in an assisted procreation program and 8 were
      included three or more times in these programs, for a total of 41 cycles of
      assisted reproduction: all these cycles were characterized by a negative result.
      All 19 patients were treated by diagnostic-operative laparoscopy: a salpingectomy
      was carried out after a hydrosalpinx in all these cases. RESULTS: All patients
      were treated with 2 assisted reproduction cycles, which were made with a variable
      range of time from 3 to 6 months after laparoscopic surgery, totalizing 38
      cycles. At present, 4 pregnancies have been obtained (pregnancy rate = 22%): this
      value is comparable to the values obtained in the best assisted reproduction
      programs. CONCLUSIONS: Many studies showed that hydrosglpinx presence reduces
      very much FIVET procedures. There are many cases showing that the hydrosalpinx
      become worse, if it has not been preventively treated, during assisted
      reproduction programs. Moreover complications during FIVET programs in the
      presence of hydrosalpinx are observed. Even if this study is based on data
      related to a small number of patients, it's clear that surgical treatment of
      severe tubarian pathology can give the best results where an assisted
      reproduction program will be surely unsuccessful.

PMID- 11310147
TI  - [Evaluation of partners of women with HPV infection].
AB  - BACKGROUND: The authors report the results of a clinical-peniscopic study of the
      genital regions in the male sexual partners of woman with proven genital Human
      Papilloma Virus (HPV) infection because of its contagiousness, incidence rate and
      relation with premalignant lesions. METHODS: From January 1998 to March 1999, 137
      sex partners of women with HPV genital infection were investigated by clinical
      evaluation, cytologic examination of a urethral brushing and peniscopy at the
      Cervico-vaginal Pathology Center of the Gynecology and Obstetrics Institute of
      the Second University of Naples. All patients with a clinical and/or peniscopic
      evidence of infection were submitted to biopsy for histologic examination.
      RESULTS: On peniscopy 29.9% (41 patients) of men presented lesions either typical
      of suspicious for HPV infection at the first and/or at the second control.
      CONCLUSIONS: These data confirm that HPV infection, as all sexually transmitted
      diseases, needs a prevention and control program involving male and female to
      obtain a good recovery rate and a lowest diffusion.

PMID- 11310148
TI  - [Influence of ovarian cysts during controlled ovarian hyperstimulation].
AB  - BACKGROUND: The use of gonadotrophin-releasing hormone agonist and purified
      follicular stimulating hormone increases the incidence of ovarian cysts during in
      vitro fertilization-embryo transfer cycles. The aetiopathogenesis and the effects
      of ovarian cysts on controlled ovarian hyperstimulation is unclear; most authors
      observed no-detrimental influence of ovarian cysts in controlled ovarian
      hyperstimulation cycles for IVF. The aim of this study was the evaluation of the
      real incidence and effects of ovarian cysts during in vitro fertilization-embryo
      transfer cycles. METHODS:  DESIGN: retrospective study. SETTING: reproductive
      medicine units. PATIENTS: 130 women. INTERVENTIONS: r-FSH--225 U.I. was
      administered to 130 women i.m. after a long protocol of down regulation with GnRH
      a (Triptoreline 3.75). The drug administration was personalized on the basis of:
      pre-existent patients pathologies; E2 blood levels; ultrasound evaluation of the
      follicular development. MAIN OUTCOME MEASURES: E2 levels, number and quality of
      oocytes retrieved, fertilization rate, number of embryos developed, pregnancy
      rate. RESULTS: At the end of stimulation ovarian cyst was observed in eighteen
      cases. There was no difference, between the cycles with or without cysts, in the
      follicular development, number and quality of eggs retrieved, fertilization rate,
      number and quality of the transferred embryos, pregnancy and miscarriage rate.
      CONCLUSIONS: The conclusion is drawn that the incidence of ovarian cysts during
      COH can be reduced observing some simple rules like: to exclude from the
      stimulation protocols patients with follicles of more than 12 mm diameters as
      observed at the preliminary ultrasound control; to personalize the therapeutic
      regime with the pre-existent patients pathologies; ultrasound evaluation of the
      follicular development; determination of the E2 serum levels, every two days.

PMID- 11310151
TI  - [Emergency splenectomy in pregnancy complicated with idiopathic
      thrombocytopenia].
AB  - Thrombocytopenia can be a pathophysiological feature of pregnancy and spontaneous
      splenic rupture in pregnancy is a rare and potentially catastrophic event. A case
      of splenic rupture after cesarean delivery, performed for increasing
      thrombocytopenia is reported. The diagnosis was not suspected until laparotomy.
      Low transverse cesarean birth required a vertical extension of the incision into
      the upper uterine segment. An emergency splenectomy was undertaken without
      complications. The operation was followed by a massive increase in the
      thrombocyte count. Both mother and baby are in good health 10 months later. The
      newborn had a normal thrombocyte count at delivery and thereafter. The importance
      of early diagnosis and management techniques are discussed.

PMID- 11310149
TI  - [Current role of progesterone therapy in the prevention of spontaneous abortion
      and in the treatment of threatened abortion].
AB  - Progesterone therapy is often used to prevent spontaneous abortion. In this paper
      the most significant studies on the benefits and risks of this treatment over the
      last 30 years are analyzed. None of these studies about the effects of
      progesterone as non-specific therapy in abortion risk and recurrent miscarriage,
      proved a reduced pregnancy wastage in treated patients compared with patients who
      received no treatment. The results concerning the use of progesterone in
      recurrent miscarriage for luteal phase inadequacy are more controversial, but
      they are still inadequate to encourage progesterone supplementation. To obtain a
      definitive conclusion about progesterone therapy real effectiveness, it is
      necessary to carry out randomized double-blind prospected trials. As regards the
      risks of using progesterone therapy during pregnancy, even if a possible
      teratologic role has certainly been reduced, it cannot be excluded completely
      yet. Moreover a high incidence of respiratory problems has been noticed in
      newborns from patients treated with progesterone, compared with control groups.

PMID- 11310152
TI  - [Medical and ethical considerations on multiple pregnancies following the use of
      assisted fertilization techniques. A current problem].

PMID- 11310150
TI  - [Endometrial adenocarcinoma appearing during tamoxifen therapy. Report of a
      clinical case].
AB  - Tamoxifen is a non-steroid estrogenic antagonist, used in post-surgical therapy
      of breast cancer. It interferes with endocrinous promotion of breast cancer.
      Tamoxifen could determine endometrial, even carcinomatous, alterations. The case
      of a postmenopausal patient surgically treated for breast cancer and successively
      treated with tamoxifen (20 mg/die), is reported. She underwent ultrasonographic
      and hysterosonographic endometrial evaluation and finally a hysterectomy with
      bilateral annessiectomy. This case seems to confirm tamoxifen possible
      carcinogenical effects on the endometrium.

PMID- 11310153
TI  - Prognostic models in medicine. AI and statistical approaches.

PMID- 11310154
TI  - Nonparametric selection method of survival predictors with an application to
      breast cancer.
AB  - Mutual information between a survival variable and covariables provides a new
      tool for selecting covariables with a high predictive value whenever there is no
      reasonable parametric model with respect to the observed phenomena. The
      information rate carried out by covariables can be tested by means of a
      decomposition similar to the analysis of variance. Moreover, a method based on
      information conservation can be used for aggregating survival curves
      corresponding to different modalities of the same selected predictor which
      increases the prediction efficiency. These results are applied to survival data
      from 1304 patients with breast cancer followed over a period of ten years.

PMID- 11310155
TI  - On prognostic models, artificial intelligence and censored observations.
AB  - The development of prognostic models for assisting medical practitioners with
      decision making is not a trivial task. Models need to possess a number of
      desirable characteristics and few, if any, current modelling approaches based on
      statistical or artificial intelligence can produce models that display all these
      characteristics. The inability of modelling techniques to provide truly useful
      models has led to interest in these models being purely academic in nature. This
      in turn has resulted in only a very small percentage of models that have been
      developed being deployed in practice. On the other hand, new modelling paradigms
      are being proposed continuously within the machine learning and statistical
      community and claims, often based on inadequate evaluation, being made on their
      superiority over traditional modelling methods. We believe that for new modelling
      approaches to deliver true net benefits over traditional techniques, an
      evaluation centric approach to their development is essential. In this paper we
      present such an evaluation centric approach to developing extensions to the basic
      k-nearest neighbour (k-NN) paradigm. We use standard statistical techniques to
      enhance the distance metric used and a framework based on evidence theory to
      obtain a prediction for the target example from the outcome of the retrieved
      exemplars. We refer to this new k-NN algorithm as Censored k-NN (Ck-NN). This
      reflects the enhancements made to k-NN that are aimed at providing a means for
      handling censored observations within k-NN.

PMID- 11310156
TI  - Predicting patient's long-term clinical status after hip arthroplasty using
      hierarchical decision modelling and data mining.
AB  - Construction of a prognostic model is presented for the long-term outcome after
      femoral neck fracture treatment with implantation of hip endoprosthesis. While
      the model is induced from the follow-up data, we show that the use of additional
      expert knowledge is absolutely crucial to obtain good predictive accuracy. A
      schema is proposed where domain knowledge is encoded as a hierarchical decision
      model of which only a part is induced from the data while the rest is specified
      by the expert. Although applied to hip endoprosthesis domain, the proposed schema
      is general and can be used for the construction of other prognostic models where
      both follow-up data and human expertise is available.

PMID- 11310157
TI  - Effects of case removal in prognostic models.
AB  - Constructing and updating prognostic models that learn from training cases is a
      time-consuming task. The more compact, and yet informative, the training sets
      are, the faster one can build and properly evaluate such models. We have compared
      different regression diagnostic methods for selection and removal of training
      cases in prognostic models. Univariate determinations were performed using
      classical regression diagnostic statistics. Multivariate determinations were
      performed using (1) a sequential "backward" selection of cases, and (2) a non
      sequential genetic algorithm. The genetic algorithm produced final models that
      kept few cases and retained predictive capability. A genetic algorithm approach
      to case selection may be better suited for guiding removal of cases in training
      sets than a univariate or a sequential multivariate approach, possibly because of
      its ability to detect sets of cases that are influential en bloc but may not be
      sufficiently influential when considered in isolation.

PMID- 11310158
TI  - Robust outcome prediction for intensive-care patients.
AB  - Missing data are a major plague of medical databases in general, and of Intensive
      Care Unit databases in particular. The time pressure of work in an Intensive Care
      Unit pushes the physicians to omit randomly or selectively record data. These
      different omission strategies give rise to different patterns of missing data and
      the recommended approach of completing the database using median imputation and
      fitting a logistic regression model can lead to significant biases. This paper
      applies a new classification method, called robust Bayes classifier, which does
      not rely on any particular assumption about the pattern of missing data and
      compares it to the median imputation approach using a database of 324 Intensive
      Care Unit patients.

PMID- 11310159
TI  - Individual prognosis of diabetes long-term risks: a CBR approach.
AB  - We present DIRAS, an application to support physicians in determining the risk of
      complications for individual diabetic patients. The risk pattern of each diabetic
      patient is obtained using a Case-based Reasoning method called LID. Case-based
      Reasoning is an Artificial Intelligence technique based on solving new situations
      according to past experiences. For each patient, the LID method determines the
      risk of each diabetic complication according to the risk of already diagnosed
      patients. In addition, LID builds a description that can be viewed as an
      explanation of the obtained risk.

PMID- 11310160
TI  - Prognosis of body fluid level by fuzzy logic technique.
AB  - Surgical fluid replacement is a critical issue in medicine as the fluid volume
      excess or deficit can both complicate the patient's condition. Currently, the
      administration of fluid volume is carried out primarily based on the experience
      and expertise of the anaesthetist as there is no analytical method available to
      estimate the patient's fluid level. The development of a decision support system
      (DSS) to assist the anaesthetist in estimating the required fluid infusion rate
      for a particular patient has been the focus of this research paper. The DSS is
      developed based on Fuzzy Logic Control (FLC) technique which is ideal for
      developing input/output models in an unstructured and/or complex environment. The
      fuzzy rules used in the DSS are derived automatically from the clinical data
      produced in surgical operations. The DSS employs a Multi Rule Base (MRB) learning
      scheme to adapt its model according to the significant variation in the
      physiological parameters of a patient. The performance of the developed
      algorithms is validated through experimental work using clinical data. The
      results obtained so far are encouraging.

PMID- 11310161
TI  - Identification of patients at high cardiovascular risk: a critical appraisal of
      applicability of statistical risk prediction models.
AB  - Assessment of cardiovascular risk is widely proposed as a basis for taking
      management decisions about patients presenting with hypertension or
      hypercholesterolemia. Our aim was to critically assess the use of risk equations
      derived from epidemiological studies for the purpose of identifying high-risk
      patients. Risk equations were retrieved from the MEDLINE database and then
      applied to a data set of 118 patients. This data set was an evaluation study of
      the clinical value of the World Health Organization 1993 hypertension guidelines
      for the decision to treat mild hypertensive patients. We calculated agreement: 1)
      between equations and 2) between equations and the decision to treat taken by the
      physician. Most models were not applicable to our population, mainly because the
      original population had a narrow age range or comprised only males. Between-model
      agreement was better for the lower and upper risk quintiles than for the three
      other risk quintiles (0.58, 0.33, 0.34, 0.45, 0.70, from the lower to the upper
      risk quintile). When using an arbitrary threshold for defining high-risk patients
      (i.e. > 2% per year), we observed a huge variation of the proportion of patients
      classified at high risk (from 0 to 17%). There was a poor agreement between risk
      models and the decision to treat taken by the physician. These results suggest
      that risk-based guidelines should be validated before their diffusion.

PMID- 11310163
TI  - Investigation of brain dynamics in Parkinson's disease by methods derived from
      nonlinear dynamics.
AB  - EEGs were recorded from patients in early stages of Parkinson's disease (17
      patients, 9 females) and healthy controls (12 subjects, 8 females) during rest
      and during execution/imagining of a complex motor task. The prediction that
      Parkinson's disease patients compared to controls would show more complex brain
      dynamics during performance of a complex motor task and imagination of the
      movements was confirmed by methods derived from nonlinear dynamics. In the
      resting state, analysis of correlation dimension of EEG time series revealed only
      slight topographical differences between the groups. During performance of a
      complex motor task, however, data from Parkinson's disease patients showed higher
      dimensionality than data from controls, indicating more complex EEG time series.
      The same difference was found when subjects did not perform any motor movements
      but imagined the complex movements they had just performed. The data are
      consistent with the hypothesis that the disturbances in Parkinson's disease
      result in the recruitment of superfluous cortical networks due to failed
      inhibition of alternative motor programs in the striatum and thus increase the
      complexity of cortical representation in motor conditions.

PMID- 11310164
TI  - Mechanoreceptive afferents in the human sural nerve.
AB  - Microneurography was used to characterize 104 low-threshold mechanoreceptive
      afferents in the human sural nerve. The afferents were readily classified into
      four types using criteria developed for the glabrous skin of the hand: SA I
      (31%), SA II (11%), FA I (49%), and FA II (9%). The distribution of fascicle
      fields and receptive fields of individual afferents on the lateral side of the
      foot indicates that the glabrous skin portion of the innervation territory of the
      sural nerve is more densely innervated than the non-glabrous skin portion. The
      different populations in the glabrous and non-glabrous skin regions were similar
      regarding proportion of unit types, receptive field sizes, and force thresholds.
      The receptive field sizes of the type I units of the present sample were about
      twice the size compared to those of the glabrous hand units, and the force
      threshold were at least three times higher for three of the unit types (SA I, FA
      I, and FA II). Given their receptive properties, it is likely that
      mechanoreceptive afferents in the sural nerve provide rich information about
      contact patterns between the foot and environment during stance and locomotion.

PMID- 11310162
TI  - Activated astrocytes in areas of kainate-induced neuronal injury upregulate the
      expression of the metabotropic glutamate receptors 2/3 and 5.
AB  - All forms of brain injury induce activation of astrocytes, although different
      types of injury induce different astrocytic responses. Activated astrocytes are
      characterised by hypertrophy, proliferation and increased expression of glial
      fibrillary acidic protein (GFAP). However, neither the process by which
      astrocytes become reactive nor the consequences are well understood. Recently,
      the application of specific growth factors to primary astrocytic cultures was
      shown to regulate dramatically the level of expression of the metabotropic
      glutamate receptors (mGluR) 5 and 3. In the present study, we have used an
      intracerebroventricular injection of a subconvulsive dose of kainic acid to
      produce a lesion of CA3a pyramidal neurones in the mouse hippocampus and to
      investigate whether mGluR expression was altered in reactive astrocytes in vivo.
      Immunohistochemical analysis showed strong mGluR5 and mGluR2/3 immunoreactivity
      in glial cells within the area of neuronal loss possessing the morphological
      feature of activated astrocytes. Double labelling with GFAP confirmed the
      expression of mGluRs by reactive astrocytes. The mechanical injury produced by
      the needle insertion in the cerebral cortex also produced enhanced expression of
      mGluR5 and mGluR2/3 in activated astrocytes proximal to the area of neuronal
      injury. Our finding of an increased mGluR expression in reactive astrocytes in
      vivo suggests that transcriptional regulation by specific growth factors on
      mGluRs is a phenomenon extendible to specific circumstances in vivo and not
      limited to in vitro models. Identification of the mechanisms of this adaptive
      plasticity will be central in the understanding of the events leading to neuronal
      survival and/or death.

PMID- 11310165
TI  - Movement discrimination by single cells in the human pallidum characterised by
      hidden Markov models.
AB  - In patients undergoing pallidotomy for Parkinson's disease, we recorded
      extracellularly from single neurons in the two internal segments (GPii, GPie) and
      the external segment (GPe) of the globus pallidus (GP) in response to active
      (cued) movements of the contralateral wrist, elbow or ankle. The patterns of cell
      activity occurring both before and after movement onset were analysed using
      hidden Markov models (HMMs) and clustered by movement type using the generative
      topographical mapping algorithm. Cluster separation was quantified in order to
      measure a cell's ability to discriminate between movements. Statistical analysis
      of variance indicated a significant regional gradient (GPii > GPie > GPe) of
      movement discrimination, while cells in all regions differentiated better between
      movements of different joints (wrist, elbow or ankle) than between flexion and
      extension of the same joint. We found that GP cells generally showed
      distinguishable firing patterns corresponding to more than one type of movement
      per cell, in support of the hypothesis that cells in these regions of the basal
      ganglia are not involved in preparation or execution of a single type of movement
      but participate in many different movements, analogous to the hidden units of a
      neural network. Our results also indicate that cell activity both preceding a
      movement and during its execution may be modelled by HMMs with only a small
      number of states.

PMID- 11310166
TI  - Dynamic visual acuity during transient and sinusoidal yaw rotation in normal and
      unilaterally vestibulopathic humans.
AB  - The vestibulo-ocular reflex (VOR) stabilizes gaze to permit clear vision during
      head movements. It has been supposed that VOR function might be inferred from
      dynamic visual acuity (DVA), the acuity during imposed head motion. We sought to
      determine effectiveness of DVA for detection and lateralization of unilateral
      vestibulopathy, using rigorous psychophysical methods. Seventeen normal and 11
      unilaterally vestibulopathic subjects underwent measurement of optically best
      corrected DVA during head motion. A variable size letter "E" 6 m distant was
      displayed in oblique random orientations to determine binocular DVA by a computer
      controlled, forced choice method. Three types of whole-body yaw rotation were
      delivered by a servo-controlled chair synchronized with optotype presentation.
      Two types of motion were predictable: (1) steady-state 2.0-Hz rotation at 10-130
      degrees/s peak velocity with repetitive optotype presentation only during head
      velocity exceeding 80% of peak; and (2) directionally predictable transients at
      peak accelerations of 1000, 1600 and 2800 degrees/s2 with optotype presentation
      for 300 ms. For neither of these predictable motions did DVA in vestibulopathic
      subjects significantly differ from normal, with suggestions from search coil
      recordings that this was due to predictive slow and saccadic eye movements.
      Unilaterally vestibulopathic subjects experienced a significant decrease in DVA
      from the static condition during ipsilesional rotation for all three peak head
      accelerations. Only during directionally unpredictable transients with 75 ms or
      300 ms optotype presentation was the sensitivity of DVA in unilaterally
      vestibulopathic subjects significantly abnormal during ipsilesional rotation. The
      ipsilesional decrease in DVA with head motion was greater for 75 ms than 300 ms
      optotype presentation. Search coil recordings confirmed hypometric compensatory
      eye movements during DVA testing with unpredictable, ipsilesional rotation.
      Receiver-operator characteristic analysis indicated ideal detection and
      lateralization of unilateral vestibulopathy by DVA tested with a 75-ms optotype
      exposure for unpredictable transient rotations to a peak acceleration of 2800
      degrees/s. DVA can reliably detect unilateral deafferentation only if precautions
      are taken to prevent compensation by predictive slow eye movements and saccades.

PMID- 11310167
TI  - Dyslexia and the centre-of-gravity effect.
AB  - When human observers are presented with a double target display, a saccadic eye
      movement is triggered to an intermediate position close to the 'centre-of
      gravity' of the configuration. This study examined the saccadic eye movements of
      dyslexic and normal readers in response to displays of single and double targets.
      Eye movement analyses revealed no differences in the spatial position of saccadic
      eye movements of dyslexic and normal readers in response to single targets
      presented at 5 degrees or 10 degrees. However, when presented with two targets
      simultaneously at 5 degrees AND 10 degrees, in contrast to normal readers who
      generated saccades to an intermediate position between the two targets (towards
      the 'centre-of gravity'), dyslexics generated saccades that landed close to the
      near target eccentricity. These findings suggest that dyslexia is associated with
      a deficit in the processing of global spatial information for the control of
      saccadic eye movements.

PMID- 11310168
TI  - Modulation of presynaptic inhibition of la afferents during voluntary wrist
      flexion and extension in man.
AB  - Changes in presynaptic inhibition of Ia terminals directed to flexor carpi
      radialis (FCR) motoneurones (MNs) were investigated in normal human subjects at
      rest and during voluntary wrist flexion and extension. To that end, two
      independent methods were used: (1) the radial-induced D1 inhibition of the FCR H
      reflex, which assesses the excitability of PAD (primary afferent depolarisation)
      interneurones controlling presynaptic inhibition of Ia terminals mediating the
      afferent volley of the FCR H reflex; and (2) the heteronymous monosynaptic Ia
      facilitation induced in the FCR H reflex by intrinsic muscle Ia afferent
      stimulation, which assesses the ongoing presynaptic inhibition of Ia terminals.
      With respect to results at rest, it was found that at the onset of (and during
      tonic) voluntary wrist flexion, D1 inhibition was reduced and heteronymous
      monosynaptic Ia facilitation was increased. This suggests that, as in the lower
      limb, presynaptic inhibition is decreased on Ia terminals projecting to MNs
      involved in the voluntary contraction. In contrast with results observed in the
      lower limb, presynaptic inhibition of Ia terminals to FCR MNs was also found to
      be reduced at the onset of a voluntary contraction involving the antagonistic
      wrist extensors, suggesting that presynaptic inhibition of Ia terminals
      projecting to wrist flexors and extensors might be mediated through the same
      subsets of PAD interneurones. This is in keeping with other features showing that
      the organisation of reflex pathways between wrist flexors and extensors differs
      from that observed at other (elbow, ankle) joints.

PMID- 11310169
TI  - Location and distribution of Fos protein expression in rat hippocampus following
      acute moderate aerobic exercise.
AB  - Hippocampal neurons are activated during endurance exercise; however, little
      attention has been given to the location and spatial distribution of these
      neurons. We have, therefore, used Fos protein expression to identify the location
      and distribution of hippocampal neurons that become activated during acute
      moderate aerobic exercise. Adult rats were assigned into trained running (TR),
      trained nonrunning (TNR), untrained nonrunning (UNR), and cage-bound (CB) groups.
      Rats in the TR and TNR groups were trained to run, for three 20-min running
      periods separated by 3 min rest, on a treadmill. Rats in the UNR group spent
      identical time on a nonactivated treadmill, while rats in the CB group remained
      in their home cages throughout the training and experimentation. After training
      to criterion performance for both TR and TNR groups, both groups were rested for
      1 day. Rats in the TR were then run on the treadmill to criterion level, while
      those in TNR and UNR groups spent equivalent time on the nonactivated treadmill.
      Animals in all groups were then killed and their brains removed, sectioned, and
      processed for Fos protein immunocytochemistry. Fos-like immunoreactive (FLI)
      neurons were counted in the dentate and CA1-3 fields of the hippocampus. The
      total numbers of hippocampal FLI neurons, as well as FLI neurons in each
      hippocampal region, were compared among groups. The total numbers of FLI neurons
      in the hippocampus, as well as in individual regions, were significantly greater
      in the TR group compared with the other three groups. Similarly, significant
      differences were found between the TNR group when compared with UNR and CB
      groups. Conversely, a significant difference existed between UNR and CB only in
      the CA1 field, which may account for the significant difference in the total
      number of hippocampal FLI neurons between these two groups. These results show
      that Fos induction occurs in the hippocampus during moderate physical exercise.
      Furthermore, the importance of the incorporation of adequate controls to account
      for possible differences in expression of immediate early gene expression due to
      trained performing, trained nonperforming, and untrained groups is discussed. The
      results indicate that adequate control for nonexercise stimuli is necessary for
      studies of the effect of exercise on the brain when expression of immediate early
      genes such as c-fos is used as an outcome measure.

PMID- 11310170
TI  - Influence of stimulus color on the control of reaching-grasping movements.
AB  - This kinematic study aimed to determine whether color is a stimulus property
      involved in the control of reaching-grasping movements. Subjects reached and
      grasped a target-object, located either on the right or on the left of the
      subject's midline. A distractor, placed along the subject's midline, could be
      randomly presented. The colors, i.e., both chromaticity (red and green stimuli
      were presented) and lightness, of the target and distractor were varied in
      experiment 1. Only stimulus lightness and only stimulus chromaticity were varied
      in experiments 2 and 3, respectively. In experiment 4 subjects matched with their
      thumb and index finger the size of the target-stimuli presented in experiment 1.
      Chromaticity (experiments 1 and 3) of the target and distractor influenced grasp,
      but not reach. Maximal finger aperture was larger during grasping the red than
      the green target. Data collected in the matching task (experiment 4) confirmed a
      trend to overestimate the red target and to underestimate the green one. During
      grasp, hand shaping was influenced by distractor chromaticity when it was
      different from target chromaticity. Distractor lightness affected reach, but not
      grasp (experiments 1 and 2). Reach was slower when the distractor was lighter and
      arm trajectory veered away from it. The results of the present study suggest that
      color, that is the ensemble of chromaticity and lightness, is a stimulus property
      involved in the control of reaching-grasping. The different effects of target
      color on reach and grasp support the notion that intrinsic object properties,
      such as color, affect grasp more than reach. In addition, the different effects
      of distractor chromaticity and lightness on reach and grasp confirm that target
      objects are visually extracted from surrounding cues by means of different
      processes, according to the required motor response.

PMID- 11310171
TI  - Inactivation of macaque lateral intraparietal area delays initiation of the
      second saccade predominantly from contralesional eye positions in a double
      saccade task.
AB  - Previous studies have shown that, although lateral intraparietal (LIP) area
      neurons have retinotopic receptive fields, the response strength of these cells
      is modulated by eye position. This combining of retinal and eye position
      information can form a distributed coding of target locations in a head-centered
      coordinate frame. Such an implicit head-centered coding offers one mechanism for
      maintaining spatial stability across eye movements and can be used to compute new
      oculomotor error vectors after each eye movement. An alternative mechanism is to
      use eye displacement signals rather than eye position signals to maintain spatial
      stability. The aim of this study was to distinguish which of these two extra
      retinal signals (or perhaps both signals) are employed in a double saccade task,
      which required the monkey to use extraretinal information associated with the
      first saccade to localize a remembered target for a second saccade. By varying
      the direction and the end point of the first saccade and selectively inactivating
      area LIP in one hemisphere with muscimol injection, we were able to distinguish
      between the two mechanisms by observing how the second saccade was impaired in
      this task. The displacement mechanism predicts that, if the first saccade is in
      the contralesional direction, the second saccade will be impaired, and the end
      point of the first saccade would not be important. The eye position mechanism
      predicts that if the first saccade ended in the contralesional head-centered
      space, the second saccade will be impaired, no matter in which direction the
      first saccade is made. Results showed that, after area LIP lesion, when the first
      saccade stepped into the contralesional field, the error rate of the second
      saccade became higher and the latency longer. However, when the end point of the
      first saccade was constant, the direction of the first saccade had much less
      effect on the second saccade. These results suggest that eye position, and not
      eye displacement, is the more predominant factor in this task. In a different
      behavioral paradigm, the monkeys performed single visual and memory saccades from
      different initial eye positions. It was found that the impairment of either the
      metrics or dynamics of visual and memory saccades did not significantly vary with
      the different eye positions. It thus appears that the performance of single
      visual and memory saccades is best described in an oculocentric coordinate frame
      that does not rely on extraretinal signals. Altogether these results lend further
      support to the hypothesis that, by combining retinal and eye position signals,
      area LIP contains concurrent eye-centered and head-centered representations of
      the visual space. Depending on the task, either representation can be used.

PMID- 11310172
TI  - The effect of muscle length on motor-unit recruitment during isometric plantar
      flexion in humans.
AB  - The triceps surae muscle group, consisting of the mono-articular soleus (SOL) and
      bi-articular gastrocnemius (GAS) muscles, primarily generates plantar flexor
      torque. Since the GAS muscle crosses the knee joint, flexion of the knee reduces
      the length of this muscle, thus limiting its contribution to torque output.
      However, it is not clearly understood how the central nervous system activates
      muscles that are at inefficient or non-optimal force-producing lengths.
      Therefore, the present study was designed to determine the effect of muscle
      length on motor-unit recruitment in the medial GAS muscle. Single motor-unit
      activity was recorded from the medial GAS muscle while electromyographic (EMG)
      activity was recorded from the SOL muscle in nine male subjects. With the ankle
      angle held constant at 90 degrees, the knee angle was changed from 180 degrees to
      90 degrees, corresponding to a long and short GAS muscle length, respectively.
      Levels of voluntary plantar flexor torque were produced at a rate of 2 Nm.s-1
      until motor-unit activity was detected. A total of 229 motor units were recorded,
      of which 121 and 108 were obtained at the long and short muscle lengths,
      respectively. At the short length, onset of motor-unit activity occurred at
      significantly higher levels of plantar flexor torque and SOL EMG. Onset of motor
      unit activity occurred at 2.97 +/- 7.78 Nm and 32.14 +/- 10.25 Nm, corresponding
      to 0.045 +/- 0.075 mV and 0.231 +/- 0.129 mV of SOL EMG in the long and short
      positions, respectively. No individual GAS motor unit could be recorded at both
      muscle lengths. Motor units in the shortened GAS muscle may be influenced by
      peripheral afferents capable of reducing the excitability of the motoneurone
      pool. This may also reflect a specific inhibition of motor units having
      shortened, non-optimal fascicle lengths, and they are thereby incapable of
      contributing to plantar flexor torque.

PMID- 11310173
TI  - Task-dependent control of human masseter muscles from ipsilateral and
      contralateral motor cortex.
AB  - Corticotrigeminal projections to human masseter motoneuron pools were
      investigated with focal transcranial magnetic stimulation (TMS). Responses in
      left and right masseter muscles were quantified from the surface electromyogram
      (EMG) during different biting tasks. During bilateral biting, TMS elicited motor
      evoked potentials (MEPs) in both masseter muscles. On average, the MEP area in
      the masseter contralateral to the stimulus was 39% larger than in the ipsilateral
      muscle, despite comparable pre-stimulus EMG in both muscles. MEPs elicited while
      subjects attempted unilateral activation of one masseter muscle were compared
      with those obtained in the same muscle during a bilateral bite at an equivalent
      EMG level. MEPs in the masseter contralateral to the stimulated hemisphere were
      significantly smaller during unilateral compared with bilateral biting. There was
      no significant difference in the size of ipsilateral MEPs during ipsilateral and
      bilateral biting. We conclude that the corticotrigeminal projections to masseter
      are bilateral, with a stronger contralateral projection. The command for
      unilateral biting is associated with a reduced excitability of corticotrigeminal
      neurons in the contralateral, but not the ipsilateral motor cortex. We suggest
      that this may be accomplished by reduced activity of a population of
      corticotrigeminal neurons which branch to innervate both masseter motoneuron
      pools.

PMID- 11310174
TI  - Long-term cholinergic enhancement of evoked potentials in rat hindlimb
      somatosensory cortex displays characteristics of long-term potentiation.
AB  - Pairing a cutaneous electrical stimulus of the hind-paw with stimulation of the
      basal forebrain produces long-term cholinergic enhancement of the responsiveness
      to a tactile stimulus. A short period of pairing (20 trials) increased the area
      of the two main components of the evoked potential by 37.1 +/- 13.5% (+/- SEM)
      and 37.9 +/- 6.8%, respectively. The effects lasted for the duration of the
      experiment (> 2 h). The enhancement could be blocked by either MK-801, an NMDA
      receptor antagonist or by L-NAME, a nitric-oxide-synthase inhibitor when they
      were given prior to pairing. Control experiments with skin stimulation alone and
      basal forebrain stimulation alone had only small long-term effects (approximately
      10%) on the size of the evoked potential. Thus, long-term cholinergic
      enhancement, attributable to disinhibition and increased release of acetylcholine
      in the cortex during neuronal excitation by other sources, and so named because
      it is blocked by atropine, may be a form of long-term potentiation. The existence
      of such a mechanism for the control of cortical neuronal plasticity identifies
      the basal forebrain as a powerful modulator of long-lasting changes in cortical
      neuronal excitability.

PMID- 11310175
TI  - Perineuronal nets show intrinsic patterns of extracellular matrix differentiation
      in organotypic slice cultures.
AB  - Perineuronal nets (PNs), consisting of extracellular matrix proteoglycans,
      complexed with hyaluronan and colocalized with tenascins, are associated with
      distinct neuronal populations in mature mammalian brain. PNs have been shown to
      appear postnatally during the period of synaptic refinement and myelination,
      indicating the commencement of mature physiological properties of neurons. Here
      we show that the developmental patterns of formation of PNs are well preserved in
      organotypic slice cultures prepared from rats on postnatal day 3-5 and maintained
      in vitro for 3-10 weeks. Staining of cultures with Wisteria floribunda agglutinin
      and immunocytochemical detection of chondroitin sulfate proteoglycans revealed
      developing PNs in the basal forebrain, mesencephalic regions, and the cerebellum
      after 2 weeks in vitro, and later in the neocortical areas and hippocampus. In
      contrast, neurons known to be devoid of PNs in the adult rat brain such as
      cholinergic basal forebrain neurons and catecholaminergic tegmental neurons
      differentiate without any formation of PNs in slice cultures. We show further
      that environmental factors influence the development of PNs around the net
      associated types of neurons. Notably, chronic depolarization of the cultures,
      imposed by an elevated concentration of external potassium ions, enhanced the
      development of PNs. Blocking of calcium channels with magnesium chloride or with
      the L-type calcium channel blocker nifedipine, suppressed the development of PNs,
      while a block of voltage-gated sodium channels by tetrodotoxin had no obvious
      effects. The results show that extracellular matrix components specifically
      contribute to the organotypic patterns that develop in brain slice cultures.
      Evidence is provided that the differentiation of PNs is regulated by calcium
      dependent signaling.

PMID- 11310176
TI  - Reduction in inflammation-induced sensitization of dorsal horn neurons by
      transcutaneous electrical nerve stimulation in anesthetized rats.
AB  - Transcutaneous electrical nerve stimulation (TENS) is utilized to treat a variety
      of painful conditions. Inflamed animals present with an increased response to
      noxious stimuli, i.e., hyperalgesia, at the site of injury (primary hyperalgesia)
      and outside the site of injury (secondary hyperalgesia). Further, following acute
      inflammation, dorsal horn neurons show an increased responsiveness to
      peripherally applied stimuli, which has been termed sensitization. Previous
      studies demonstrate a reduction in dorsal horn neuron activity following TENS
      treatment in normal animals and a reduction in primary and secondary hyperalgesia
      in acutely inflamed animals. The purpose of this study was to examine the effects
      of TENS on dorsal horn neurons sensitized by acute inflammation. Extracellular
      recordings from wide dynamic range (WDR), high threshold (HT) and low threshold
      (LT) dorsal horn neurons in anesthetized rats were assessed for spontaneous
      activity, responses to innocuous and noxious mechanical stimulation and receptive
      field size. Responses were measured before and 3 h after induction of
      inflammation, and immediately and 1 h after application of either high (100 Hz)
      or low (4 Hz) frequency TENS (motor intensity, pulse duration = 100
      microseconds). TENS was applied to the inflamed paw to encompass the receptive
      field of the neuron for 20 min. WDR and HT dorsal horn neurons sensitized to
      mechanical stimulation after induction of inflammation. Application of either
      high or low frequency TENS to the inflamed paw reduced both innocuous and noxious
      evoked responses of WDR and HT dorsal horn neurons immediately and 1 h after
      treatment with TENS. Comparison of responses after TENS with baseline responses
      showed that the evoked responses in the majority of WDR and HT cells returned to
      or fell below baseline responses. TENS had no effect on responses of LT neurons.
      In summary, central neuron sensitization is reduced by TENS and may underlie the
      reduction in hyperalgesia observed after treatment with TENS.

PMID- 11310177
TI  - Using thiazolidinediones: rosiglitazone and pioglitazone in clinical practice.
AB  - Type 2 diabetes is a disorder that has numerous components, including insulin
      resistance, an insulin secretory defect, and an increase in hepatic glucose
      production. Until recently, only the insulin secretory defect could be treated.
      Within recent years, the thiazolidinedione (TZD) class of drugs, which targets
      primarily insulin resistance, was released. Originally developed in Japan as
      triglyceride-lowering agents, TZDs were found to be more effective in lowering
      blood glucose levels instead. The actions of 2 TZDs--rosiglitazone and
      pioglitazone--are discussed, and their glucose- and nonglucose-lowering effects
      are explained. Four case histories are presented to illustrate various patients'
      responses to TZDs in clinical practice. Although TZDs have been demonstrated to
      be effective in dealing with many different aspects of type 2 diabetes, further
      study, involving multiple clinical trials, is needed.

PMID- 11310178
TI  - [Gallbladder carcinoma and laparoscopic cholecystectomy. An emergent problem].
AB  - BACKGROUND: Gallbladder cancer (GC) is reported in 1.5-3% of cholecystectomies.
      Since the introduction of laparoscopic surgery, cholecystectomies have increased
      and occult GC may therefore be more frequent. METHODS: Here we conduct a
      retrospective study on a series of 1200 LC performed between January 1991 and
      December 1998 at our Institution, to determine whether there was an increase in
      GC. We also evaluated the risk factors for this outcome and the possibilities of
      treatment, in case of unsuspected GC discovered after LC at histological
      examination. Seven cases of GC undiagnosed before surgery (0.6% of the study
      population) were submitted to LC (against 0.3% GC discovered after open surgery).
      The clinical course depended on the histopathologic stage of the cancer. RESULTS:
      After a median follow-up of 18 months (range 12-48), 2 pT1 patients were alive
      and well, 2 pT2 patients were alive and disease free (in 1 case after a surgical
      removal of a trocar site metastasis appeared 6 months after LC). The other 3
      patients died, 2 (1 pT2 and 1 pT3) after an additional resection of the liver bed
      with lymph node dissection, due to peritoneal dissemination of the disease. In 2
      cases we found a gallbladder polyp pre and intraoperatively, which proved to be a
      carcinoma. CONCLUSIONS: Undiagnosed GC is on the increase with the introduction
      of LC. Polypoid lesions of the gallbladder, age > 70 years: a long history of
      stones and a thickened gallbladder wall all represent significant risk factors.
      If one or more is present, examination of the gallbladder and a frozen section
      are recommended.

PMID- 11310179
TI  - [Results of the use of endoprostheses in the treatment of retained common bile
      duct stones].
AB  - BACKGROUND: The value of endoprostheses for long term management of bile duct
      stones has not been formally established. A retrospective evaluation of results
      and complications of the insertion of biliary endoprostheses was performed in
      patients with endoscopic irretrievable bile duct stones. METHODS: From January
      1990 to September 1999, 52 patients (19 men and 33 women; average age 76 years),
      underwent endoscopic biliary stenting for endoscopically irretrievable bile duct
      stones. RESULTS: Successful biliary drainage was achieved in 50/52 (96.1%)
      patients. Early complications occurred in 11.5% of cases. Over the long term
      follow-up (average follow-up = 39.5 months) late complications occurred in 40.8%
      of cases, with 3 cases of biliary-related death. CONCLUSIONS: For immediate bile
      duct drainage, endoprostheses proved a safe and effective alternative for
      treatment of patients with endoscopically irretrievable bile duct stones. Because
      of the risk of subsequent complications, its use as a definitive treatment should
      be confirmed to highly selected cases.

PMID- 11310180
TI  - [Video thoracoscopic treatment in pleural empyema].
AB  - BACKGROUND: To evaluate the possible role and the effectiveness of
      videothoracoscopy (VATS) in the treatment of pleural empyema. METHODS: Personal
      experience on 40 cases of pleural empyema treated by (VATS) during 5 years is
      reported. The underlying diseases were: pneumonia (32), pneumothorax (3),
      tuberculosis (2), abdominal diseases (2) and lung cancer (1). Before VATS at
      least one thoracentesis was performed to evaluate the characteristic of the
      pleural fluid. RESULTS: Due to complications related to thick pleural adhesions,
      in one case (2.5%) the procedure was converted to open surgery, while in the
      remaining 39 cases VATS was able to achieve a complete cleaning of the pleural
      space with re-expansion of the pulmonary parenchyma. The improvement of the
      clinical symptoms were observed after a mean period of 3.5 days (range: 1-12
      days). Chest tube was removed in a mean period of 4.8 days (range: 3-11 days);
      five patients had prolonged air leak from 6 to 10 days after surgery.
      CONCLUSIONS: In conclusion we are of the opinion that VATS has to be considered a
      very important mean for the treatment of pleural empyema; its use in the
      fibrinopurulent phase of the disease should give very good results, while in the
      following phase its indications are controversial.

PMID- 11310181
TI  - [Surgical repair of pectus excavatum by internal metal strut fixation. Clinical
      experience in 51 cases].
AB  - BACKGROUND: Broad is the spectrum of congenital chest wall deformities.
      Fortunately the severe life-threatening deformities (i.e. ectopia cordis and
      Jeune's disease) are rarer than the more frequent pectus excavatum and carinatum.
      Funnel chest is the most common anterior chest wall deformity, it results from
      posterior depression of the sternum and cartilages, from the third to the eighth;
      it occurs more frequently in boys than in girls (4:1 ratio). While the deformity
      may be recognizable at birth, especially during crying spells, it progressively
      worsens during childhood, producing, sometimes, respiratory and cardiac
      impairment. METHODS: The authors report their experience, from April 1970 to
      December 1998, in correction of Pectus Excavatum using a single surgical
      technique, at the Borgo Roma Hospital of Verona. During this period 51 patients
      (mean age 14 years) affected by this deformity, were treated performing a sterno
      chondroplasty with internal fixation. Most of the patients (94%) required
      operation for the esthetic and psychological reasons only. The grade of funnel
      chest (according to the Chin Classification) was: type I in 59.6% of patients,
      type II in 31.4% and type III in 11.7%. The surgical technique consisted in the
      modification of the Ravitch's technique (subperichondrial cartilage resection,
      transverse osteotomy with internal stainless steel strut fixation). We considered
      the intervention advisable to correct an existing defect or to prevent its
      progression. We don't think, in fact, that spontaneous recession of the deformity
      may occur. RESULTS: The follow-up varied from 4 to 18 years. The result was
      classified according to the classification of Humphreys and it was excellent in
      64.7%, good in 17.7%, fair in 9.8% and poor in 7.8%. CONCLUSIONS: This technique
      proved to be safe and effective, it can be performed with no mortality, very low
      complication rate and satisfactory results.

PMID- 11310182
TI  - [Vascular trauma of the lower limbs].
AB  - BACKGROUND: This study was conducted to evaluate the results of treatment of
      vascular trauma of the lower extremities and those factors associated with limb
      loss. DESIGN: a retrospective evaluation of a series with lower extremities
      vascular trauma. SETTING: University Hospital. METHODS: Thirty-one patients
      accounting for 45 vascular lesions of the lower extremities (27 arterial and 18
      venous injuries), over a 15 years period ending December 1998. Age, sex, modality
      of the trauma, site of the lesion and associated skeletal injuries, diagnostic
      procedures, ischemic time, arterial and venous repair performed were analyzed.
      RESULTS: Perioperative mortality was 7.4%. For arterial injuries, limb salvage
      was obtained in 22 patients (81.5%). Five amputations (18.5%), 1 primary and 4
      secondary have been performed. Amputation rate was 26.7% for popliteal lesions
      versus 8.3% for other locations, 40% when a skeletal lesion was associated versus
      5.9% for those without such injuries, 37.5% for reverse saphenous vein
      interpositions versus 5.6% for arterial repair without interposition.
      CONCLUSIONS: In this study, the factors influencing limb loss in vascular trauma
      of the lower extremities are popliteal location, the association with skeletal
      injuries, the need of saphenous vein interposition for arterial repair.

PMID- 11310183
TI  - [Cervical lymphadenitis caused by mycobacteria. Our experience].
AB  - BACKGROUND: Mycobacterial infections are extremely complex diseases, either due
      to the various clinical manifestations, or to the various involved kind of
      mycobacteria, or to the different sensibility to antibiotics. The authors review
      retrospectively their series, evaluating the management of pediatric cervical
      lymphadenitis due to mycobacterical etiology. METHODS: From 1975 to 1998, at the
      Department of Pediatric Surgery of the university of Siena, 88 children were
      evaluated for laterocervical lymphadenopathy. Among these, 29 children, aged from
      14 months to 13 years, were diagnosed as affected with lymphoadenopathy due to
      mycobacteria. Therapy of choice was the association of surgery and antibiotics.
      This behaviour allowed us to approach both advanced lesions, in active
      colliquation, and progressive ones. RESULTS: Results were unquestionably
      positive, with a complete resolution and good esthetical results in 93.2% of
      cases. In 6.8% of cases there was a recurrence, which required reintervention.
      CONCLUSIONS: On the basis of our series, we agree with the international
      literature in affirming that, in cases of mycobacterial lymphadenopathy, a
      combined antibiotic and surgical therapy is necessary. However, controversy about
      such a complex and difficult pathology is opened and unsolved.

PMID- 11310184
TI  - [Gastrointestinal stromal tumors (GIST). Our experience].
AB  - Nine cases of gastrointestinal stromal tumors (GISTs) observed in the period
      between 1993 and 1999 and treated with radical surgery are presented. Patients
      were studied with instrumental examinations (ultrasonography, TC, EGDS, RSCS,
      endoscopic ultra-sound) which permitted to make a temporary diagnosis of "suspect
      gastric or bowel neoplasm". Only after surgical resection of the neoplasm it was
      possible to make a definitive diagnosis, based on histologic examination of the
      operating piece. According to personal experience and literature data, we could
      affirm that GISTs' clinical manifestations are extremely heterogeneous and so
      these tumors are often diagnosed casually. Prognosis isn't correlated as much to
      neoplasm histologic and cytologic characteristics, as to next organs
      infiltration, which represents a sign of particular aggressiveness of lesions.

PMID- 11310185
TI  - [Closed thoracic trauma. Considerations on surgical treatment of flail chest].
AB  - Two cases of thoracic injuries with flail chest are described. Particularly, the
      indications and management of surgical treatment, of flail chest are discussed.
      It is important not to reconstitute the anatomic structure of the chest, but to
      recover the physiological respiratory motion. Today, the first choice is the
      mechanical ventilation, even if it needs a long period of time and sometimes it
      has some complications. The surgical treatment is absolute only when other
      thoracic lesion i.e. massive hemothorax, pulmonary, tracheal and bronchial
      injuries) joined the flail chest. Often the surgical management follows the
      ventilation therapy; in these cases, thoracotomy is better made in five or six
      days after trauma. Today, the Kirschner pins or Judet plates are used for
      fixation. Sometimes, when injury is considerable synthetic meshes are also used.

PMID- 11310186
TI  - [Spontaneous pneumomediastinum: radiologic and CT study].
AB  - Pneumomediastinum may be due to various diseases. In young adults without
      thoracic trauma or pulmonary or mediastinal diseases pneumomediastium is
      secondary to mild strain or cough. This disease is defined as spontaneous
      pneumomediastinum or Hamman's syndrome, with a good prognosis, and doesn't need
      any treatment. X-ray and CT of the chest can provide correct diagnosis and
      adequate treatment.

PMID- 11310187
TI  - [Boerhaave syndrome. A case report and review of the literature].
AB  - Spontaneous esophageal perforation (Boerhaave's syndrome) remains a difficult
      diagnostic and management problem with controversial recommendations regarding
      its treatment. The clinical manifestations of the disease are variable, and may
      be misleading, thus delaying accurate recognition. On the other hand, in view of
      the rapid onset of severe complications, particularly mediastinitis, a prompt
      diagnosis is essential to a better prognosis, successful operative outcome and
      potential survival. A case of spontaneous perforation of the thoracic esophagus
      penetrating the left pleural space treated within 4 hours from admission to the
      Emergency Room, with minimal surgical intervention is presented. Despite negative
      chest X-ray, a thoracic TC showed a small right sided effusion with left sided
      hydropneumothorax, and the definitive diagnosis was obtained by contrast study
      with a water soluble medium which showed the leak communicating freely with the
      left pleural space. The patient underwent repair by thoracic approach, the
      rupture was closed with a primary suture without flap reinforcement and the
      pleural space drained with the placement of single chest thoracostomy tube. The
      recovery was uneventful. The analysis of this case report and of the appropriate
      literature reveals that a poor prognosis is correlated with the time elapsed
      between the perforation and treatment. In conclusion the importance of an early
      aggressive surgical treatment for the Boerhaave's syndrome is emphasized, because
      any perforation treated more than 24 hours after the onset of symptoms,
      irrespective of the procedure used, is associated with a significantly higher
      morbility and mortality.

PMID- 11310188
TI  - [Nonprogressive, late-onset atrophy of the cheek].
AB  - Lipodystrophies are rare conditions in which the most remarkable feature is an
      atrophy of the subcutaneous tissues. Until two decades ago, they were all
      considered under the name of "lipoatrophic diabetes", and only recently they have
      been properly classified. Currently four syndromes are recognized: congenital
      total lipodystrophy, late onset or acquired lipodystrophy, cephalothoracic or
      partial progressive lipodystrophy and partial face-sparing lipodystrophy. We
      report the case of a 73-year-old patient, long distance bus driver, who presented
      to our clinic for the correction of a malar atrophy located on the left side of
      his face. Until he was 48 years old his appearance was normal, but at the time he
      reports the slow onset of a facial atrophy which was confined to the cheek. The
      atrophy was very slowly progressing, so that at this moment at 73 years of age he
      presented to our observation for the correction of the asymmetry. Clinical
      examination and history oriented us towards a variation of Parry-Romberg's
      syndrome characterized by a non progressive late onset hemifacial atrophy. No
      muscle or bony involvement is present. No other important abnormalities,
      excluding a moderate hyperglycemia have been observed. A biopsy of the region
      shows a marked elastosis and a complete atrophy of the subcutaneous fat.
      Correction of the deformity was achieved with autologous fat injection and was
      still satisfactory after one year.

PMID- 11310189
TI  - Indirect cost of ischemic heart disease to employers.

PMID- 11310190
TI  - Cost-sharing for prescriptions of sildenafil and finasteride: a case study in
      veteran patients.
AB  - OBJECTIVE: To evaluate patients willingness to share the costs of 2 medications
      (often described as "lifestyle medications"): sildenafil for erectile dysfunction
      and finasteride for hair loss, which are not routinely covered by the Department
      of Veterans Affairs (VA) healthcare system. STUDY DESIGN: Self-administered,
      anonymous survey. PATIENTS AND METHODS: Adult men (n = 339) were recruited from
      waiting rooms for primary care or erectile dysfunction clinic appointments at 2
      Los Angeles VA facilities. RESULTS: Participants with self-reported need were
      analyzed separately for finasteride (primary care patients only) and sildenafil
      (both primary care and erectile dysfunction clinic patients). The mean age of the
      participants was 56 and 60 years for the finasteride and sildenafil groups,
      respectively. Mean annual household income for both groups was under $10,000.
      Respondents reported a mean willingness to cost-share $4.20 for a 30-day
      prescription of daily finasteride (VA wholesale cost = $27) and $5.40 for 4
      sildenafil pills (VA wholesale cost = $20). In the multivariate analysis, higher
      income (P = .002) and increasing self-reported need for medication (P = .04) were
      associated with increased willingness to cost-share for finasteride after
      controlling for age, race/ethnicity, insured status, comorbid conditions, and
      type of clinic. In addition, younger age (P = .01) was associated with greater
      willingness to cost-share for sildenafil. CONCLUSIONS: In this low-income veteran
      population, patients with a self-reported need for sildenafil and finasteride
      would be willing to make a higher copayment than the current VA maximum copayment
      of $2.00 per 30-day prescription, if these medicines were made available.

PMID- 11310191
TI  - Effects of compensation method on physician behaviors.
AB  - OBJECTIVE: To examine physician and leader perceptions of the relationship
      between physician compensation and the productivity of physicians practicing in
      medical groups. STUDY DESIGN: Key informant interviews identified subjects'
      perceptions of factors influencing physician productivity and the behavioral
      effects of individual financial incentives. Interview transcripts were analyzed
      by a team of physicians, economists, and other researchers. STUDY POPULATION:
      Physicians, medical leaders, and group practice administrators (n = 114)
      representing 46 medical group practices in California, Oregon, Washington, and
      Wisconsin were interviewed. RESULTS: Five major themes emerged: (1) Most
      physicians reported that financial incentives did not substantially affect their
      own behavior, except for productivity. However, they suggested that specific
      compensation models do lead to certain seemingly undesirable physician behaviors.
      (2) By contrast, medical group leaders reported that financial incentives do
      affect a variety of physician behaviors. (3) Four productivity drivers emerged:
      financial incentives, demand-side factors, systems and infrastructure, and other
      individual or group attributes. (4) Physician compensation systems are evolving
      toward a blend of production-based and production-neutral incentives, plus new
      metrics aligned with the demands of managed care. (5) Culture, size, and
      specialty mix are significant determinants of group physician compensation
      systems. CONCLUSIONS: Compensation method is perceived to be a significant
      influence on physician productivity, particularly among group practice leaders.
      The changing context of medical practice represents another powerful "macro"
      lever on physician behavior.

PMID- 11310192
TI  - Healthy pregnancy program in a national managed care organization: evaluation of
      satisfaction and health behavior outcomes.
AB  - OBJECTIVE: To evaluate satisfaction with the Healthy Pregnancy Program (HPP),
      which was developed to educate and coordinate the care of pregnant women in a
      managed care setting. STUDY DESIGN: Telephone survey. PATIENTS AND METHODS: A
      random sample of program participants at 3 large health plans were contacted by
      telephone to evaluate their satisfaction with the program overall and with its
      components, including an educational booklet and telephone contact with a HPP
      nurse as needed. Women also were asked about changes in health behaviors
      (smoking, alcohol use, diet, and stress) resulting directly from participation in
      the HPP. Of 1155 eligible women participating in HPP who delivered a baby from
      April 1997 through March 1998, 684 completed the survey. The response rate was
      59%. RESULTS: Overall satisfaction with the HPP was reported by 96% of the women,
      and 76% reported the 2 highest ratings of satisfaction (completely or very
      satisfied). Reports of satisfaction were more likely for women who entered the
      program early in pregnancy, who read the booklet, and who had more telephone
      contacts. In general, at least half of the women in each behavior category
      reported improving their behavior, especially if they were younger, identified as
      high risk, or having their first child. Verbatim comments supported the high
      satisfaction levels. CONCLUSIONS: The HPP is an example of a program that was
      developed to improve healthcare delivery in a managed care setting and, when
      evaluated, was found to result in highly satisfied mothers likely to improve
      their health behaviors.

PMID- 11310193
TI  - Impact of poorly controlled hypertension on healthcare resource utilization and
      cost.
AB  - OBJECTIVE: To examine the relation between blood pressure (BP) control and
      utilization and cost of healthcare resources. STUDY DESIGN: A retrospective
      database study of managed care patients in New Mexico from January 1, 1996, to
      December 31, 1997. PATIENTS AND METHODS: We stratified 1000 hypertensive patients
      into categories based on average and maximum BP. Antihypertensive medication use
      and cost, number of physician visits, and interval between hypertension-related
      physician visits were determined. RESULTS: Medication costs increased
      progressively across all BP categories from lowest to highest, and higher average
      systolic BP (SBP) was significantly correlated with increased cost (P < .001).
      There were significant correlations between higher maximum BP and greater number
      of hypertension-related physician visits (P < .001). Mean number of visits for BP
      groups was 5.5 for patients with a maximum diastolic BP (DBP) < 85 mm Hg and 10.0
      for those with a maximum DBP > or = 100 mm Hg (P < .001). Patients with a maximum
      SBP > or = 180 mm Hg averaged 9.7 visits, whereas those with a maximum SBP < 120
      mm Hg averaged 4.1 visits (P < .001). Both SBP and DBP were significantly
      correlated with time to next visit (P < .001). Mean visit intervals ranged from
      44 days for patients with an SBP < 85 mm Hg to 25 days for those with an SBP > or
      = 180 mm Hg (P < .001). A similar association was found between DBP and visit
      interval. CONCLUSIONS: Poor control of hypertension is associated with higher
      drug costs and more physician visits. Aggressive treatment might help reduce
      managed care costs and resource utilization.

PMID- 11310194
TI  - The effect of nonsteroidal anti-inflammatory drugs on the use of gastroprotective
      medication in people with arthritis.
AB  - OBJECTIVE: To estimate the incidence of gastroprotective medication use among
      users and nonusers of prescription nonsteroidal anti-inflammatory drugs (NSAIDs)
      who have arthritis. STUDY DESIGN: A retrospective cohort study. PATIENTS AND
      METHODS: We used the Protocare Sciences proprietary Managed Care Organization
      database, which contains data on more than 3 million lives, to identify 57,136
      patients given an initial diagnosis of osteoarthritis (OA; International
      Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM]
      codes: 715, 721.0, 721.3, or 721.9) or rheumatoid arthritis (RA; ICD-9-CM codes:
      714.0, 714.1, 714.2, or 714.9); the diagnoses were made during inpatient or
      outpatient medical encounters occurring between October 1, 1993, and September
      30, 1997. The duration of therapy was calculated as the sum of the total number
      of days of receipt of all prescriptions during the year. The prescribed daily
      dose was determined by multiplying the drug dose by the number of pills dispensed
      and the dividing the product by the number of days supplied, as noted in the
      pharmacy records. RESULTS: During the year after NSAID initiation, 27% of people
      with RA and 12% of those with OA were chronic NSAID users. NSAID users with RA
      were 4 times as likely as NSAID nonusers with RA to begin using a
      gastroprotective agent within the first year; NSAID users with OA were twice as
      likely as nonusers with OA to do so. CONCLUSION: The use of gastroprotective
      agents during the first year after NSAID initiation for the treatment of
      arthritis was greater than their use by those who did not take NSAIDs.

PMID- 11310195
TI  - Achieving control of diabetic risk factors in primary care settings.

PMID- 11310196
TI  - De novo malignant transformation of giant cell tumor of bone.
AB  - Two cases of malignant lesions are reported, both of which arose secondary to an
      originally benign giant cell tumor (GCT) of bone. The first case was a typical
      benign GCT, which occurred in the left proximal tibia of a 31-year-old woman. The
      tumor was treated by curettage and bone grafting. However, it recurred twice
      during 15 years of follow-up. The second recurrence showed that the lesion
      histologically had turned into malignant fibrous histiocytoma. The second case
      also started as an initially benign GCT that arose in the left distal femur of a
      41-year-old man. The patient underwent curettage and bone grafting. The lesion
      recurred 13 years postoperatively. The histological appearance of the recurrent
      tumor showed it to be an osteogenic sarcoma. In both patients, radiation and
      never been given. Malignant transformation has rarely been reported in patients
      with GCT of bone who have not received radiation treatment.

PMID- 11310197
TI  - Schwannomatosis of the sciatic nerve.
AB  - A 52-year-old woman with schwannomatosis in the left sciatic nerve is presented.
      The patient had no stigmata of neurofibromatosis (NF) type 1 or 2. Cutaneous or
      spinal schwannomas were not detected. Magnetic resonance (MR) imaging of the
      sciatic nerve revealed more than 15 tumors along the course of the nerve.
      Histological examination revealed schwannomas consisting of Antoni A and B areas.
      Immunohistochemical study showed most cells reacting intensely for S-100 protein.
      The patient underwent conservative follow-up treatment due to the minimal
      symptoms. The relationship of the disease with NF-2 and plexiform schwannoma is
      discussed.

PMID- 11310198
TI  - Impingement fracture of the anteromedial tibial margin: a radiographic sign of
      combined posterolateral complex and posterior cruciate ligament disruption.
AB  - Marginal fractures of the tibial plateau are associated with a high incidence of
      soft tissue injuries to the stabilising structures of the knee joint. Injuries to
      the anterior cruciate ligament are associated with the Segond fracture and
      impingement fractures of the posteromedial tibial plateau. Recognition of these
      fractures aids diagnosis of these injuries. Marginal fractures of the tibial
      plateau associated with posterior cruciate ligament injuries are less common,
      though recently a "reverse" Segond fracture has been recognised. We describe a
      fracture of the anteromedial tibial plateau associated with complete disruption
      of the posterior cruciate ligament and posterolateral complex.

PMID- 11310199
TI  - Radiological diagnosis of abductor denervation after hip surgery.
AB  - A case of total hip arthroplasty through a direct lateral approach is described.
      The patient had a markedly positive Trendelenburg test at follow-up. Radiographs
      showed features consistent with the denervation of the gluteus medius. This was
      confirmed on CT scan. The standard post-operative radiograph following a total
      hip replacement may suggest denervation of the gluteus medius.

PMID- 11310200
TI  - MRI abnormalities of foot and ankle in asymptomatic, physically active
      individuals.
AB  - OBJECTIVE: To assess MRI changes in the ankle and foot after physical exercise.
      DESIGN AND PATIENTS: Nineteen non-professional marathon runners and 19 age- and
      sex-matched controls volunteered for the study. All had ankle and foot MR images
      (1.5 T) taken in three perpendicular planes (STIR, T2F and T1FS sequences) within
      3 h of running a full-length marathon (42.125 km). Three radiologists
      independently analysed the groups on a masked basis using a predefined form.
      RESULTS: Severe bone marrow oedema was seen in one and slight bone marrow oedema
      in three marathon runners. Slight bone marrow oedema was found in three control
      subjects. Signal alteration within the soleus muscle, consistent with a grade 1
      strain, was found in one marathon runner. Small punctate hyperintensities within
      the Achilles tendon were seen in 26% of the marathon runners and in 63% of
      controls (P = 0.016). An increased amount of fluid in the retrocalcaneal bursa
      was found in one control and in none of the marathon runners. Small amounts of
      fluid in the retrocalcaneal bursa were seen in 68% of marathon runners and in 53%
      of controls. Grade 1 or 2 peritendinous joint fluid was found around 22% of
      tendons, among both marathon runners and controls, most often involving the
      tendon sheath of the flexor hallucis longus muscle. An increased amount of joint
      fluid was noted in 34% of the joints of the marathon runners, and in 18% of the
      controls. CONCLUSION: MRI shows several abnormalities in the ankle and foot both
      after marathon races and in asymptomatic physically active individuals without
      any preceding extraordinary strain. Recreational sports may lead to a number of
      positive MRI findings without correlation with clinical findings.

PMID- 11310201
TI  - Increased signal intensity on fat-suppressed three-dimensional T1-weighted pulse
      sequences in patellar tendon: magic angle effect?
AB  - OBJECTIVE: To assess the frequency of increased signal intensity in the patellar
      tendon using three-dimensional T1-weighted MRI pulse sequences. DESIGN AND
      PATIENTS: Sixty patients were examined with a 1.0 T scanner (15 mT/m gradient
      strength) using a quadrature coil. Three pulse sequences were applied in the
      sagittal plane: PD turbo spin echo (PD-TSE), 3D T1-weighted gradient echo with
      fat suppression (3D-T1-FFE-FS) and 3D T1-weighted echo planar imaging with fat
      suppression (3D-T1-EPI-FS). The high signal intensity areas were measured in
      their maximum length. The angle of the patellar tendon relative to the main field
      position was measured in the same slice. In eight patients with anterior knee
      pain, and in 11 with no anterior knee pain, a fourth T2-weighted TSE pulse
      sequence (T2-TSE) was obtained to rule out patellar tendinitis. RESULTS: The
      correlation of the high signal intensity areas with the relative position of the
      tendon was found to be significant with the 3D sequences (P = 0.03 for 3D-T1-FFE
      FS and P = 0.003 for 3D-T1-EPI-FS). The length of the high signal intensity area
      in the tendon was 5.4 mm with 3D-T1-FFE-FS, 4.9 mm with 3D-T1-EPI-FS and 3.1 mm
      with PD-TSE images. No patellar tendinitis was demonstrated on the T2-TSE images.
      CONCLUSION: The magic angle effect is commonly observed in the 3D based T1
      weighted pulse sequences with fat suppression. The presence of the above sign
      must be recognized by radiologists, so that misdiagnosis of patellar tendinitis
      is avoided.

PMID- 11310202
TI  - MR imaging of the knee in marathon runners before and after competition.
AB  - OBJECTIVE: To evaluate the findings in MRI-studies of the knee in recreational
      long-distance runners after competition and to assess the reversibility of the
      findings. DESIGN AND PATIENTS: Eight recreational long-distance runners underwent
      MRI studies of the knee before, immediately after and 6-8 weeks after taking part
      in the Vienna City Marathon. The studies were evaluated regarding alterations of
      pre-existing lesions and new pathological findings. RESULTS: In six runners
      without major pre-existing alterations no negative effects were experienced. In
      one runner with pre-existing grade III alterations of the menisci, signs of
      progressive osteoarthritis were experienced 2 months after the competition. In
      all other cases increased meniscal signal alterations and minor signal changes in
      the bone marrow after the race were transitory. CONCLUSION: In healthy
      individuals no negative long-term-effects were experienced. Pre-existing high
      grade lesions of the menisci might be a predisposing risk for osteoarthritis,
      triggered by the stress of long-distance running.

PMID- 11310203
TI  - The internal calcar septum (femoral thigh spur) in computed tomography and
      conventional radiography.
AB  - OBJECTIVE: The femoral "thigh spur", a cortical septum in the region of the
      lesser trochanter of the human femur, was first described and named by the German
      anatomist Merkel in 1874, but it was never examined in detail. To evaluate the
      frequency and the shape of this structure, a combined anatomical and radiological
      study was performed using saw-cuts from specimens, high-resolution CT and
      conventional radiography. DESIGN: Thirty human cadaveric femora of central
      European origin were analyzed by high-precision computed tomography (CT) using
      thin slices and high-resolution imaging. The CT data were image processed with
      thresholding to obtain a reconstruction of high-density bone formations and for
      three-dimensional imaging. Additionally three macerated femur specimens were cut
      exactly corresponding to the CT slices. The computed images were validated with
      the anatomical saw-cuts. RESULTS: A dense trabecular ridge protruding endosteally
      from the posteromedial cortex was found in all femora. This cortical septum
      reaching from the femoral neck to the distal part of the lesser trochanter
      separated the femoral cavity from the cancellous bone inside the lesser
      trochanter. On conventional radiography the femoral thigh spur could be
      visualized best in the frog-lateral view of the hip. CONCLUSION: The internal
      calcar septum is a constant cortical structure. It should be recognized when
      radiographs or CT images of the proximal femur are interpreted. It could be of
      importance for metaphyseal fitting of an endoprosthetic stem.

PMID- 11310204
TI  - The C sign: more specific for flatfoot deformity than subtalar coalition.
AB  - OBJECTIVE: To assess the sensitivity and specificity of the C sign, a C-shaped
      line created by the outline of the talar dome and the inferior margin of the
      sustentaculum tali on lateral ankle radiographs, for patients with both flatfoot
      deformity and specifically talocalcaneal (TC) coalition. DESIGN AND PATIENTS: All
      patients in this retrospective study were under 35 years of age and had a lateral
      ankle radiograph and follow-up CT scan for a non-traumatic indication. Forty
      eight cases over the past 5 years fulfilled these criteria. Two masked
      musculoskeletal radiologists determined the presence or absence of the C sign for
      each lateral radiograph by consensus. Each CT study was then assessed by a third
      musculoskeletal radiologist for the presence of tarsal coalition. Observations
      were correlated with clinical history regarding presence or absence of flatfoot
      deformity. RESULTS: Ten cases of TC coalition were diagnosed, four of which
      demonstrated a C sign (40%). Eight cases with a C sign were encountered, four of
      which had TC coalition (50%) and four did not. All patients with a positive C
      sign had a flatfoot clinically (100%), while only eight of 24 flatfooted patients
      had a C sign (33%). CONCLUSION: The C sign is specific, but not sensitive, for
      flatfoot deformity, and is neither sensitive nor specific for subtalar coalition.

PMID- 11310205
TI  - Wrist ligament injuries: value of post-arthrography computed tomography.
AB  - OBJECTIVE: To evaluate the use of post-arthrography high-resolution computed
      tomography in wrist ligament injuries. DESIGN AND PATIENTS: Thirty-six
      consecutive patients who had a history and clinical findings suggestive of
      ligamentous injuries of the wrist were prospectively studied. The findings of
      three-compartment arthrography and post-arthrography computed tomography (arthro
      CT) were compared with those of arthroscopy. The evaluation concentrates on the
      detection and precise localization of ligament lesions in the triangular
      fibrocartilage (TFC), the scapholunate ligament (SLL) and the lunotriquetral
      ligament (LTL). RESULTS: For TFC, SLL and LTL lesions, standard arthrography
      responded with a sensitivity and specificity of 85% and 100%, 85% and 100%, 80%
      and 100% respectively, while arthro-CT showed a sensitivity and specificity of
      85% and 100%, 100% and 100%, 80% and 100% respectively. The precise localization
      of the lesions was possible only with arthro-CT. CONCLUSION: The sensitivity and
      specificity of standard arthrography and arthro-CT are similar, although the
      latter shows the site of tears or perforation with greater precision, while
      conventional arthrography demonstrates them indirectly. This precision is
      essential and may have clinical implications for the success of treatment
      procedures.

PMID- 11310206
TI  - The effect of an osteolytic tumor on the three-dimensional trabecular bone
      morphology in an animal model.
AB  - OBJECTIVE: To investigate the application of micro-computed tomography (microCT)
      for the assessment of density differences and deterioration of three-dimensional
      architecture of trabecular bone in an experimental rat model for tumor-induced
      osteolytic defects. DESIGN AND MATERIALS: Walker carcinosarcoma 256 malignant
      breast cancer cells (W256) were surgically implanted into the medullary canal of
      the left femur of 15 4-month-old rats. Twenty-eight days after surgery all
      animals were killed and both femora from each rat were harvested. A total of 30
      specimens (left and right femur) were scanned in a desktop microCT imaging system
      (microCT 20, Scanco Medical) to assess densitometric and architectural
      parameters. For each specimen a total of 200 micro-tomographic slices with a
      resolution of 30 microns in the distal metaphysis was taken. Bone mineral content
      (BMC) was analyzed for both cortical and trabecular bone (ctBMC), and for
      trabecular bone only (tBMC). Architectural indices (BV/TV, Tb.N, Tb.Th, Tb.Sp)
      according to standard definitions used in histomorphometry were calculated for
      trabecular bone. RESULTS: The quantitative analysis of density parameters
      revealed significantly (P < 0.001) lower values for ctBMC and tBMC in the tumor
      bearing group (T) of 26% and 31%, respectively, compared with the contralateral
      control group. The quantitative analysis revealed significant (P < 0.001) changes
      in the architectural parameters in the tumor-bearing bones compared with the
      contralateral control group: BV/TV was 30% lower, Tb.N and BS/TV decreased by 24%
      and 21%, respectively, Tb.Th. decreased by 10% and Tb.Sp. increased by 94%.
      CONCLUSIONS: This study demonstrates that microCT is able to provide three
      dimensional parameters of bone mass and trabecular structure in an animal model
      for tumor-induced bone loss. Recent advances in therapeutic approaches for
      skeletal diseases such as osteoporosis and metastatic bone diseasse rely on an
      understanding of the effects of the agents on the mechanical properties of bone.
      In order to quantify the structural changes of the affected bones the application
      of a non-destructive method is mandatory. The use of microCT seems to be a great
      advantage, since biomechanical tests and further histologic analysis can be done
      for the same specimens.

PMID- 11310207
TI  - Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic
      osteomalacia.
AB  - Phosphaturic mesenchymal tumor is a rare neoplasm which causes osteomalacia or
      rickets. The tumor typically follows a benign clinical course. Even in the rare
      malignant cases, local recurrence and distant metastasis are uncommon. We report
      on an example of a malignant phosphaturic mesenchymal tumor which recurred
      several times over 16 years concurrently causing hypophosphatemia, bone pain, and
      osteomalacia. Following each surgery, symptoms and hypophosphatemia improved. The
      patient died of disease 17 years after the first surgery. Histologically, the
      initial tumor was composed of small spindle cells with clusters of giant cells,
      prominent blood vessels, poorly formed cartilaginous areas, and crystalline
      material. Cytological atypia was minimal. Following multiple recurrences, the
      tumor demonstrated areas of high-grade sarcoma exhibiting marked pleomorphism,
      numerous mitotic figures, and p53 overexpression. This case illustrates the
      potential lethality of incompletely removed phosphaturic mesenchymal tumors.

PMID- 11310208
TI  - Quantitative analysis of telomerase activity and telomerase reverse transcriptase
      expression in renal cell carcinoma.
AB  - To investigate the relationship between the telomerase activity levels and
      clinicopathological features of tumors, we quantified the telomerase activities
      of 23 renal cell carcinomas (RCCs) and four non-cancerous tissues, using a
      modified telomeric repeat amplification protocol assay, and assessed the hTERT
      mRNA levels of these samples by reverse transcription-polymerase chain reaction
      analysis. Elevated levels of telomerase activity had correlation with tumor
      stages as well as the degree of nuclear grades. Our findings suggested that
      telomerase activity is a useful indicator for tumor aggressiveness in RCCs.
      However, hTERT mRNA levels in RCCs had no correlation with nuclear grades and
      tumor stages. The telomerase activities and the hTERT mRNA levels in cancer cells
      were not always in parallel. These results suggested that telomerase activity is
      regulated in a posttranscriptional manner as well as a post-translational manner
      in tumor cells.

PMID- 11310209
TI  - Production and characterisation of a C595 antibody-99mTc conjugate for
      immunoscintigraphy of bladder cancer.
AB  - Current radiological techniques for staging bladder cancer are inaccurate,
      especially in the identification of pelvic lymph node metastases.
      Immunoscintigraphy has the potential to offer improved staging for bladder
      cancer. The aim of this study was to label the anti-MUC1 monoclonal antibody C595
      with 99mtechnetium (Tc), the most widely used diagnostic radionuclide, and assess
      the potential of the resultant conjugate for intravenous immunoscintigraphy of
      bladder cancer. A direct, reduction-mediated technique was used to label the
      antibody. The resultant conjugate was shown to be highly immunoreactive, stable
      and bound specifically to MUC1. The ability of the conjugate to bind to bladder
      tumours was demonstrated in an ex vivo model where the mean tumour:normal
      urothelial uptake was 5.7:1 and by intravesical administration in patients with
      bladder cancer where the mean tumour:normal urothelial uptake was 20.4:1. The
      ability of the conjugate to localise MUC1-expressing tumours was demonstrated in
      a nude mouse xenograft model. A conjugate of 99mTc-C595 has been produced and
      characterised, and it may be suitable for intravenous immunoscintigraphy, a
      potential novel staging tool for bladder cancer.

PMID- 11310210
TI  - Interferon-alpha inhibits cyclooxygenase-1 and stimulates cyclooxygenase-2
      expression in bladder cancer cells in vitro.
AB  - The enzymes cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2) catalyze the
      initial step in the formation of prostaglandins (PGs). PGs are known to be
      involved in numerous processes, for example inflammation, immune responses,
      carcinogenesis, and tumor angiogenesis. The formation of PGs is stimulated in
      various cancers since the expression of Cox-2 is upregulated. Interferon (IFN)
      alpha is used in the treatment of bladder cancer, although not all of the effects
      of such treatment are thoroughly known. Therefore, we investigated the expression
      of cyclooxygenases in two bladder cancer cell lines, 5637 and T24, under basal
      conditions and in the presence of human recombinant IFN-alpha (100, 1,000, and
      10,000 U/ml). The mRNA of Cox-1 and Cox-2 was expressed in both cultured bladder
      carcinoma cell lines. The level of Cox-1 expression was low in 5637 cells and
      higher in T24 cells. In contrast, Cox-2 expression was prominent in 5637 cells
      and low in T24 cancer cells. The highest IFN-alpha concentration (10,000 U/ml)
      decreased the expression of Cox-1 to 47 and 28% of the control levels in 5637 and
      T24 cells, respectively. In contrast, Cox-2 expression increased in both cell
      lines. In 5,637 cells, Cox-2 expression increased 1.3-fold with 10,000 U/ml of
      IFN-alpha. In T24 cells, the maximum effect was achieved by 1,000 U/ml of IFN
      alpha, which increased the expression of Cox-2 up to 2.4-fold. These findings may
      have relevance in the outcome of patients treated with IFN-alpha because
      upregulated Cox-2 expression may suppress the cell-mediated defense system. On
      the other hand, the inhibition of Cox-1 could be beneficial because Cox-1 is
      known to stimulate angiogenesis.

PMID- 11310211
TI  - Increased expression of cyclooxygenase-2 and nitric oxide synthase-2 in human
      prostate cancer.
AB  - Cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide
      synthase-2 (NOS-2) each have an important role in angiogenesis. The expression of
      these genes was investigated in human prostate cancer by immunohistochemistry,
      the expression of COX-1 and COX-2 being confirmed by mRNA analysis. Prostate
      cancer specimens from 12 patients were compared to control prostates from 13
      patients operated on for bladder carcinoma. The intensity of COX-2 and NOS-2
      immunostaining was significantly stronger in prostate cancer cells than in the
      non-malignant glandular epithelium of the control prostates. COX-2 and NOS-2 were
      clearly also expressed in the lesions of prostatic intraepithelial neoplasia
      (PIN) in control prostates. COX-2 was detected in the muscle fibres of the
      hyperplastic stroma of some control prostates. No significant difference was
      detected in COX-1 expression between control and cancer prostates. These results
      indicate that the expression of COX-2 and NOS-2 is elevated in prostatic
      adenocarcinoma and in PIN.

PMID- 11310212
TI  - Chemically induced intestinal de-epithelialization using silver nitrate for
      bladder augmentation.
AB  - The use of bowel segments for bladder augmentation has been associated with
      metabolic complications, infections, stones, and cancer at the vesicoenteric
      anastomosis. The establishment of a transitional epithelium over the de
      epithelialized surface of a segment of intestine might alleviate these
      complications. In this study, chemical de-epithelialization and urothelial re
      epithelialization were attempted using silver nitrate (AgNO3) solutions at
      different concentrations. Augmentation cystoplasty was performed in 55 female
      Swiss-Albino rats using a 1.5-cm detubularized segment of sigmoid. Forty-one rats
      survived and were killed 12 weeks postoperatively. There were four groups,
      including one group of eight rats that underwent augmentation alone (group 1,
      control), while the other three groups were treated with 1 g/100 ml (11 rats), 5
      g/100 ml (10 rats), and 10 g/100 ml (12 rats) AgNO3 solutions, respectively,
      before augmentation. Histopathological analysis demonstrated almost complete de
      epithelialization and urothelialization of the sigmoid segment treated with 10
      g/100 ml AgNO3 solution, which did not occur in the other groups. Postoperative
      bladder capacities were increased in all groups. There was no obvious
      histological difference in the level of collagen deposition and/or fibrosis in
      the augmented tissues in any of the experimental groups. We conclude that 10
      g/100 ml AgNO3 solution can be successfully used for chemical de
      epithelialization and urothelial re-epithelialization of augmented intestinal
      segments, and are worthy of further investigation.

PMID- 11310213
TI  - Renal tubular injury induced by hyperoxaluria: evaluation of apoptotic changes.
AB  - In order to evaluate the injurious effect of hyperoxaluria on renal tubular
      epithelium, as judged by apoptotic changes in the renal parenchyma, we performed
      an experimental study in 20 rabbits. In the experimental group animals (n = 10)
      severe hyperoxaluria was induced by continuous ethylene glycol (EG; 0.75%).
      Histologic alterations, including crystal formation, together with apoptotic
      changes were evaluated after 7 and 28 days. Control group animals (n = 10)
      received normal distilled drinking water. Following 7- and 28-day periods, tissue
      sections obtained from kidneys were examined histopathologically under light
      microscopy for the presence and the degree of crystal deposition in the tubular
      lumen. Apoptotic changes in renal tubular cells were examined using the terminal
      deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick and labeling
      (TUNEL) method during the same follow-up period. Crystal deposition was evident
      in the tubular lumen of tissue sections obtained during the 7-day examination
      period. During the 28-day examination period, however, these findings were found
      to be either limited or to have disappeared. In relation to apoptotic changes,
      the percentage of positive nuclei stained using the TUNEL method was from 11 to
      20% in the experimental group and 5.6% in the control group. Our findings
      indicate that both calcium oxalate (CaOx) crystals and hyperoxaluria itself may
      be injurious to renal tubular cells, as indicated by apoptotic changes. These
      changes may be responsible for the pathologic course of urolithiasis.

PMID- 11310214
TI  - Isoenzyme profile of glutathione S-transferases in human kidney.
AB  - Novel glutathione S-transferase (GST) isoenzymes, which do not bind to the
      glutathione (GSH) affinity column, were recently identified in dog kidney and dog
      renal cell lines. In humans, similar affinity flow-through GST has been
      previously found only in the urinary bladder. To ascertain whether these affinity
      flow-through GST isoenzymes also exist in the human kidney, we separated GST
      isoenzymes from five kidney samples on the basis of their affinity to GSH
      affinity resin. GSTs were further purified by anion exchange chromatography and
      chromatofocusing and characterized with specific substrates. Our results show
      that the human kidney has both affinity flow-through GST isoenzymes and those
      which bind tightly to the GSH affinity column. Purification of affinity-bound GST
      resulted in a rich profile of different isoenzymes with balanced expression of
      both anionic and cationic forms. Affinity flow-through GST was represented by one
      isoenzyme (pI-7.9) in all kidney samples tested, but one kidney specimen also
      contained another GST isoenzyme (pI-7.0). Our results for the first time show the
      presence of GST isoenzymes that do not bind to GSH-affinity resin in the human
      kidney. Although the assessment of similarity between the human kidney and
      urinary bladder affinity flow-through GST requires further elucidation, it can be
      speculated that these particular GSTs may play an important role in providing
      protection against the common carcinogens.

PMID- 11310215
TI  - The relation of urinary Tamm-Horsfall-protein on CaOx-crystallization under the
      scope of the Bonn-Risk-Index.
AB  - In previous papers we introduced the Bonn-Risk Index (BRI) as a new method of
      evaluating an individual's actual risk of forming calcium oxalate (CaOx). A
      comparison of our results with the calculated urinary relative supersaturations
      (RS) with respect to CaOx, showed that samples with similar values of RS can have
      different values of BRI. We suggested that this may reflect the individual
      influence of the urinary macromolecular constituents which are not taken into
      account at the calculation of RS. To estimate the role of macromolecules on the
      value of BRI, we examined 45 unprepared 24-h urine samples from 24 persons (16
      healthy subjects, eight CaOx stone-formers) with respect to BRI, RS, and the
      concentration of urinary Tamm-Horsfall-protein ([THP]). The crystallization
      experiments were carried out by the use of a laser-probe. Based on the data of
      BRI and RS, the effect of THP may shift from a minor promoter in stone-formers
      and persons "at risk", to an inert urinary constituent in healthy subjects and
      persons "without risk". However, the observed effects are small and at least in
      the latter group close to zero.

PMID- 11310216
TI  - Effects of citrate on renal stone formation and osteopontin expression in a rat
      urolithiasis model.
AB  - Previous studies have described the inhibitory effects of citrate on calcium
      oxalate crystallization in place of crystal growth, but the effects of citrate on
      matrix proteins of stones has not been studied in vivo. To examine the effect of
      citrate on the matrix, we investigated the effect of citrate on osteopontin (OPN)
      expression, which we had previously identified as an important stone matrix
      protein. Control rats were treated with saline while rats of the stone group were
      treated with ethylene glycol (EG) and vitamin D3, and the citrate groups (low
      dose and high-dose groups) were treated with a citrate reagent compound of sodium
      citrate and potassium citrate, in addition to EG and vitamin D3. The rate of
      renal stone formation was lower in the citrate groups than in the stone group.
      This was associated with a low expression of OPN mRNA in citrate-treated rats
      relative to that in the stone group. Citrate was effective in preventing calcium
      oxalate stone formation and reduced OPN expression in rats. Our results suggest
      that citrate prevents renal stone formation by acting against not only the
      crystal aggregation and growth of calcium oxalate but also OPN expression.

PMID- 11310217
TI  - Transrectal ultrasonography in male subfertility patients: an intra- and
      interobserver study.
AB  - The purpose of this paper was to examine whether ultrasound abnormalities of the
      prostate and seminal vesicles, which may be related to male accessory gland
      infection, are reproducible. Forty-seven men attending an infertility clinic were
      studied. Imaging findings of transrectal ultrasonography were recorded. Kappa
      (kappa)-values to determine the intra- and inter-observer variation were
      assessed. Calcifications have good intra-observer (kappa = 0.77; 95% CI: 0.59
      0.96) and good inter-observer reproducibility (kappa = 0.73; 95% CI: 0.54-0.93).
      Dilatation of the peri-prostatic plexus had moderate intra-observer (kappa =
      0.57; 95% CI: 0.33-0.80) and good inter-observer reproducibility (kappa = 0.74;
      95% CI: 0.55-0.94). Other ultrasound abnormalities of the prostate were not
      reproducible. None of the ultrasound abnormalities of the seminal vesicles were
      reproducible. In our study the prevalence of ultrasound abnormalities which may
      be related to male accessory gland infection was as high as 96%. However, only
      calcifications and dilatation of the venous plexus had good reproducibility.
      Other observed ultrasound abnormalities of the prostate and seminal vesicles were
      poorly reproducible and are therefore of no use in the diagnosis of male
      accessory gland infection.

PMID- 11310218
TI  - Viable but nonculturable uropathogenic bacteria are present in the mouse urinary
      tract following urinary tract infection and antibiotic therapy.
AB  - Involvement of the viable but nonculturable (VBNC) condition in recurrent urinary
      tract infections (UTIs) was investigated. VBNC bacteria are those which are alive
      but do not give rise to visible growth under nonselective growth conditions.
      Urine, bladder, and kidney samples collected over a 2-month period from BALB/c
      mice inoculated with the uropathogenic Escherichia coli strain J96 were examined
      to determine the level of culturable and viable bacteria. Urine from uninoculated
      mice was found to contain more viable than culturable bacteria. Inoculated mice
      had a transient increase in the level of culturable forms of the uropathogen in
      their urine, followed by a decrease to background levels; they also had multiple
      log higher levels of viable cells than culturable cells. The culturable
      pathogenic bacteria in mice that were inoculated and received antibiotic
      treatment dropped to undetectable levels within 1 week. At 2 out of 12 subsequent
      time points spanning an additional 65 days, culturable forms of the inoculated
      pathogenic bacteria were recovered. Polymerase chain reaction (PCR) analysis
      confirmed that DNA from the inoculated bacteria was present in a sample that
      yielded no culturable bacteria. These data indicate that the inoculated
      uropathogenic E. coli was not eliminated by antibiotic therapy, and suggest that
      these bacteria may escape detection by current standard culturability assays
      because they are VBNC.

PMID- 11310219
TI  - Transient urethral obstruction predisposes to ascending pyelonephritis and tubulo
      interstitial disease: studies in rats.
AB  - Chronic tubulo-interstitial disease, an important cause of end-stage renal
      disease, often results from the combined effects of a disturbed urinary outflow
      tract and urinary tract infection. Acute unilateral ureteral obstruction in rats
      rapidly induces foci of medullary necrosis, confined to the region of the papilla
      and fornices. This injury may provide a nidus for bacterial invasion and may
      invoke reactive and regenerative changes, ultimately leading to chronic
      pyelonephritis and tubulo-interstitial nephropathy. To explore this possibility,
      adult rats underwent renal morphological evaluation 2-7 days following transient
      24-h unilateral ureteral obstruction. In some experiments the bladder was
      inoculated with bacteria (10(8)-10(9) cfu/ml Escherichia coli in 0.5 ml) after
      release of ureteral obstruction, with subsequent cultures obtained from the
      pelvis of both kidneys and from the urinary bladder. Morphologic evaluation of
      perfusion-fixed kidneys, 2-7 days after the release of 24-h ureteral obstruction
      disclosed papillary necrosis, urothelial proliferation, marked inner-stripe
      interstitial expansion, and fibrosis and proximal tubular (S3) dilatation. The
      lateral (perihilar region) was predominantly affected, with lesions spreading
      from the fornices. There was some progression of interstitial fibrosis during the
      postobstructive time course or following more prolonged ureteral obstruction. By
      contrast, infection hardly contributed to the tubulointerstitial changes. In rats
      subjected to infection, cultures were positive in all 15 postobstructive kidneys,
      as opposed to five contralateral kidneys (P < 0.0001). Viable counts from the
      postobstructive kidney were also higher than those from the contralateral side
      (79,000 +/- 12,000 vs 2900 +/- 1600 cfu/ml, mean +/- SEM, P < 0.0001), and were
      comparable to those obtained from the bladder (77,000 +/- 13,000 cfu/ml). We
      conclude that transient ureteral obstruction predisposes to ascending
      pyelonephritis and to tubulointerstitial disease. This vulnerability may relate
      to altered urodynamics and medullary tissue destruction.

PMID- 11310220
TI  - Thymidine phosphorylase/platelet-derived endothelial cell growth factor (PD-ECGF)
      associated with prognosis in renal cell carcinoma.
AB  - We investigated the correlation between thymidine phosphorylase (TP)/platelet
      derived endothelial cell growth factor (PD-ECGF) expression, angiogenesis, and
      prognosis in renal cell carcinoma (RCC) patients. We prepared paraffin block
      specimens from 56 postradical nephrectomy RCC patients. The preparations were
      immunohistochemically stained using anti-CD34 antibody and anti-TP antibody.
      Angiogenic findings were evaluated based on both microvessel density (MVD) and
      renal arteriography findings as classified by Roosen et al. TP expression showed
      heterogeneity in 56 patients: 11 (19.6%) were negative, 28 (50.0%) weak, and 17
      (30.4%) positive. There was no correlation between TP expression, MVD, and renal
      arteriography. There was no TP expression in chromophobe types. Univariate
      analysis showed a significant correlation between survival and TP expression,
      patient age, tumor infiltration type, pathologic T- and N-stages, venous
      involvement, distant metastasis, and tumor grade. There was no correlation
      between survival and MVD or renal arteriography. Multivariate analysis showed a
      significant correlation between survival and pathologic T-stage, distant
      metastasis, tumor infiltration type, and TP expression. TP expression in RCC may
      be an independent prognostic factor rather than just an index for angiogenesis.

PMID- 11310221
TI  - Ageing, families and welfare systems: comparative perspectives.
AB  - Some convergence between countries may be observed in total welfare spending
      during the later decades, but while levels are becoming more similar, the
      profiles are still very different. Some welfare states are high on transfers,
      others on services, and among services--some give priority to institutions,
      others invest more heavily in community (home) care. Discussed in this article is
      how different family cultures are reflected in welfare systems, and conversely-
      how welfare systems in turn may influence families. The article argues that home
      care services tend to have lower priority in countries with familistic policies,
      and higher priority where social policies are individualistic. What model is the
      more sustainable for the future, given the social and demographic changes to be
      expected?

PMID- 11310222
TI  - The culture of aging. Individual and societal models in historico-sociological
      perspective.
AB  - When early in European history learning and internal renewal were closely
      associated with aging, the way for the Western idea of spiritual as well as
      psychological maturescence in the life course was opened up. Present improved
      material and health chances are lacking spiritual and philosophical orientations
      in and for aging. In addition, pressures for a special status and support of the
      elderly paradoxically coexist with trends towards age-irrelevance and age
      neglect. In view of such paradoxes the strengthening of the individual "locus of
      control" appears to be crucial for "creative disinhibition" and a goal
      orientation in higher age. Late life culture however may be furthered by inter-
      and intragenerational initiatives.

PMID- 11310223
TI  - Social relations and filial maturity in middle-aged adults: contextual conditions
      and psychological determinants.
AB  - The aim of this paper is to highlight the contextual and psychological
      preconditions of parent help and helpfulness in a sample of 260 middle-aged
      persons belonging to two age groups, 40-45 years and 50-55 years. In a first step
      we want to focus on the description of the contextual situation of the persons of
      this "hinge generation": What are their available social networks; what are their
      commitments towards children and parents in terms of perceived obligation and
      investment; how is their perceived balance of giving and receiving; how do they
      anticipate and experience dependency of their parents? In a second step we will
      highlight the readiness of middle-aged women and men to help their parents as
      well as the effectively reported help. Here we are interested in the
      psychological determinants of such attitude and behaviour. Structural equation
      models are performed to estimate the predictory power of personality variables,
      control beliefs and reported stress (family and job) on filial helpfulness and
      help. Results suggest that differential aspects such as gender and age group
      explain a large amount of variance of the variables intergenerational commitment
      and satisfaction with social networks and have--along with personality variables-
      a strong impact on filial help and helpfulness of middle-aged adults.

PMID- 11310224
TI  - Intergenerational solidarity and caregiving.
AB  - In this paper the topic of caregiving and intergenerational solidarity will be
      explored in four parts. First, relevant aspects of caregiving will be pointed
      out. Second, general theoretical models will be used to analyse the problem of
      caregiving. Third, the German situation and especially the still rather new long
      term care insurance will be described. Fourth and finally, the basic outline of a
      European research project (OASIS), which is devoted to the topic of
      intergenerational solidarity and the use of service systems, will be presented.

PMID- 11310225
TI  - [Options for preventing illness in the elderly].

PMID- 11310226
TI  - [Knowledge for prolonging longevity without disability].
AB  - The relationship between quality of life and aging is difficult to describe with
      the usual epidemiological concepts like mortality. A functional approach is more
      important and meaningful for the analysis of the aging process. The ICIDH
      classification has the advantage of combining the diseases process itself and the
      consequences concerning functional limitations. Studies about the "active life
      expectancy" show that quality of life and life expectancy are two different
      dimensions of the aging process. For the purpose of prevention, it is important
      to demonstrate that preventive interventions could help reduce the number of
      years with functional limitations. Most of the epidemiological studies indicate
      that even lost functions could be restored. For these interventions, it is
      important to individualize the goals for preventive measures to balance physical
      and emotional needs of the elderly.

PMID- 11310227
TI  - [Effect of physical activity on functional performance].
AB  - Epidemiological studies clearly show a connection between physical activity and
      the occurrence of disabilities in old age. Physical exercise is possible and
      useful at every age. Numerous intervention trials have shown that training of
      endurance, strength and coordination has positive effects on the cardiovascular
      system, the lung, the musculo-skeletal system, metabolism and the immune system
      in elderly people. Even very frail elderly people can increase their muscle
      strength and functional capabilities by strength training. Group sessions may
      improve social interactions and additionally increase the quality of life.

PMID- 11310228
TI  - [Information and counseling--a contribution to health promotion and health care].
AB  - Information and counselling are essential prerequisites for self-determination in
      old age. For the offers available the following differentiations are made:
      general oral, written or electronic information on supporting services,
      individual personal information and counselling, individual accompanying
      counselling and individual written information on the own health or disease
      situation. Models of good practice in Hamburg are presented as examples.

PMID- 11310229
TI  - [Geriatric care in Germany. Outline for a Hamburg decision].

PMID- 11310230
TI  - [Outline for a Hamburg decision].

PMID- 11310231
TI  - [Geriatric care in Germany--results of an empirical study].
AB  - BACKGROUND: In Germany, the situation of geriatric medicine has improved
      significantly over the past few years. Until now, though, there was little
      information available on the structure of the clinical geriatric departments.
      Since this information is vital to assess whether these departments can provide
      high-quality services, the German Federal Association of Clinical Geriatric
      Departments conducted a survey among its members. The goal was to gain deeper
      insight into the structure of the geriatric acute hospitals and rehabilitation
      units. METHODS: In 1999, member institutions were mailed a standardized
      questionnaire and all institutions (100%) returned the questionnaire to the
      association's central office. To increase data quality, data were screened and
      reports were generated for each institution. These reports were returned to the
      institutions which were asked to verify them. RESULTS: This article shows that in
      1998 acute geriatric hospitals (n = 89), rehabilitation units (n = 52), acute day
      clinics (n = 45) and rehabilitation day clinics (n = 26) had--on average-
      60/60/15.3/14 beds/places and 828.15/677.3/164.2/125.9 patients. Occupancy rates
      averaged out at 88.7%/84.3%/86.4%/63.7% and daily hospital rates at DM
      401.4/322.4/293.8/243.2. Basically, all geriatric institutions included in this
      survey had a multi-professional geriatric team. Patient-to-staff ratios for
      psychologists, social workers, ergo-, physio- and speech therapists were better
      in day clinics than in in-patient clinics and better in rehabilitation units than
      in acute hospitals. Geriatric institutions mainly focused on the treatment of
      neurological deficits. Most patients were admitted from other hospitals and
      discharged to their private residence. CONCLUSIONS: The results of this survey
      indicate that especially the acute hospitals are often not sufficiently staffed.
      Moreover, further efforts are necessary to clarify the indications for and
      modalities of geriatric day clinic treatment and rehabilitation. The data also
      show that a categorical distinction between geriatric acute hospitals and
      rehabilitation units is not possible. However, further data collection and more
      detailed analyses are needed.

PMID- 11310232
TI  - Current concepts in the treatment of hip fracture.
AB  - Clinicians involved in the care of hip fracture patients should move away from
      using treatments based on historical practices or local preferences, to those
      that are derived from careful evaluations and summaries of all previous medical
      research on that topic. For the busy clinician the use of summary articles,
      reviews and guidelines that are evidenced based are necessary to provide the best
      treatment available for the patient. Current practice indicates that the majority
      of hip fractures should be treated surgically, mobilised without restriction as
      soon as able and discharged home as soon a practicable. Given modern technology
      this should be possible for all patients.

PMID- 11310234
TI  - Chronic sorrow in caregivers of school age children with sickle cell disease: a
      grounded theory approach.
AB  - Chronic illness affects over 1 million children in the United States annually.
      One such illness prominent in the African-American population is sickle cell
      disease (SCD), which affects approximately 1 in 375 African Americans in the
      United States. This potentially life-threatening disease requires caregivers to
      carefully monitor and supervise children with SCD. Monitoring and caring for
      children with SCD places heavy burdens, demands, and responsibilities on these
      caregivers. The psychological stressors and unpredictable nature of the disease
      could cause caregivers to experience a variety of emotions, with one being
      chronic sorrow. The purposes of this study were to examine the process of chronic
      sorrow in caregivers of school age children with SCD, identify the
      characteristics of chronic sorrow, and generate a substantive theory of chronic
      sorrow. The methodology used was grounded theory, and data were generated through
      two interview sessions, a demographic questionnaire, field notes, and memos. Data
      analyses were performed following the principles of grounded theory. Data
      suggested these caregivers move through three overlapping stages: learning about
      and incorporating SCD into their daily lives; experiencing the sorrow; and doing
      what one has to do and moving on. The diagnosis was the initial trigger to evoke
      feelings, including sorrow. As time progressed, other internal and external
      triggers began to evoke feelings of sorrow that eventually became chronic. A
      process of repatterning began as caregivers learned to live with the
      unpredictable consequences of SCD, which produced the feelings of chronic sorrow.
      Repatterning behaviors enabled caregivers to "do what you have to do and move
      on."

PMID- 11310235
TI  - An anti-smoking project instituted by senior nursing students in a rural
      community.
AB  - The Health Council of Hawkins County, Tennessee, received a State Tobacco
      Prevention grant to institute an anti-smoking program in the county schools. The
      program chosen was called TarWars and encompasses a prohealth tobacco-free
      program curriculum. The goal was to discourage tobacco use among the nation's
      youth by focusing on tobacco's short-term ill effects. Because the program
      encourages community involvement, nursing students from East Tennessee State
      University, Johnson City, identified volunteers from the Hawkins County Retired
      Teachers Association to develop a teaching program for use in the first year of
      the program and as well as in subsequent years of the TarWars curriculum. A
      pretest and posttest were given to the students to assess the program's success.
      The objectives of the grant were that 80% of the students would be able to name
      three negative effects associated with tobacco use and three positive effects of
      not using tobacco. The goal was met when 91% could identify negative effects and
      89% could identify three positive effects of not using tobacco.

PMID- 11310233
TI  - The dynamics of elderly support. The transmission of solidarity patterns between
      generations.
AB  - This paper analyses the support given to the handicapped elderly by their
      children on the basis of a large survey done in France where both the elderly and
      their middle-aged children were interviewed. These data allow us to address such
      questions as: "Who helps?", "Who receives help?" and "According to what
      principles?". Besides the principle of need which is at work, the results show
      that there is also the principle of equity, which functions through reciprocity.
      This study highlights two main processes in the dynamics of support for the
      elderly, its redistributive effects (family support mainly benefits the poorest
      elderly), and its complementarity with the state health care systems (family
      support is mainly directed towards those who also receive public help). Can we
      make the deduction that the more generous the welfare state, the more developed
      family solidarity is? Nevertheless, some difficulties arise: support is mostly
      given by women. Furthermore there are a small number of people on whose shoulders
      it falls to take care of everybody else in the family. One sign of these
      difficulties is that the carers are more often in less good health than the non
      carers of the same age. Comparisons from one generation to the other, including
      the youngest (the children of the middle generation who were also interviewed)
      shows that the younger generation will not want to be so completely involved in
      parental care at the expense of their own private time and life. Most probably
      family involvement will be maintained in the future, but to a lesser extent.

PMID- 11310236
TI  - Adolescents' perceived benefits and barriers related to diabetes self-management-
      Part 1.
AB  - Knowledge is limited about adolescents' decision making regarding their
      assumption of diabetes management from parents. This study's purpose was to
      identify adolescents' perceived benefits and barriers about this process. Sixteen
      adolescents with type 1 diabetes were interviewed. Questions were adapted from
      the Janis and Mann (1977) decisional balance sheet. Interviews were audiotaped
      and transcribed verbatim. Descriptive expressions were identified and categories
      inductively generated. Adolescents' perceived benefits for themselves were having
      knowledge of or confidence in self-management abilities, more freedoms, and
      approval of others. They perceived benefits for parents as relief from
      responsibility, stress, and worry. Burden of responsibility was perceived as a
      barrier to adolescents for self-management. Adolescents perceived barriers for
      parents as worry/guilt and loss of control. Interrater agreement was initially
      74%. Categories with disagreements were recategorized by interraters and then
      there was 100% agreement. Understanding adolescents' perceptions would be
      beneficial to their health care professionals.

PMID- 11310237
TI  - Personal stories of growing up sexually.
AB  - Prevention of problems related to sexuality during adolescence continues to be a
      major public health challenge. Describing childhood perceptions of sexuality is
      an important step in understanding sexual issues during adolescence. However,
      there is a paucity of information about sexuality in early life. Therefore, the
      purpose of this study was to describe recurrent themes in personal stories of
      growing up sexually. A thematic analysis with a narrative perspective was applied
      using the method described by Miles and Huberman (1994). Four interrelated themes
      pervaded the stories: parents as teachers, sex is secret, learning by experience,
      and first intercourse as a turning point. These findings have major implications
      for sexual health education and counseling in addition to further research.

PMID- 11310238
TI  - Consumer trust--pass it on.

PMID- 11310239
TI  - Urinary fluoride excretion in children drinking fluoridated school milk.
AB  - OBJECTIVE: To determine fluoride excretion under various conditions of fluoride
      intake and to estimate the fractional urinary excretion of fluoride in individual
      children participating in a school milk fluoridation scheme. DESIGN: In the first
      part of the study, individual urine samples were collected from each of eight 4
      to 5-year-old children for a continuous period of 55 h. For each child (n = 8)
      and for each day (n = 3) the maximum urinary fluoride concentration (p.p.m.F),
      the maximum fluoride excretion rate (microgram F/h) and the total daily fluoride
      excretion (mg) were calculated. The second part of the study was carried out to
      determine the 24 h fractional percentage of fluoride excreted following
      administration of a known dose of fluoride in the absence of other sources.
      RESULTS: Under usual conditions of fluoride intake (i.e. milk containing 0.5 mg
      fluoride, customary diet and toothbrushing with fluoride toothpaste) the
      children's daily fluoride excretion was 0.33 mg. The fractional urinary fluoride
      excretion of a 0.5-mg fluoride tablet was 30%. CONCLUSIONS: It is concluded that
      the children's mean 24 h fluoride excretion was somewhere between that reported
      in low fluoride conditions and that reported in optimally fluoridated areas. The
      fractional urinary fluoride excretion was found to be in agreement with the
      findings of other workers.

PMID- 11310240
TI  - Dental caries in schoolchildren of an Estonian and a Danish municipality.
AB  - OBJECTIVES: The objectives of the study were to describe the prevalence rate and
      the severity of dental caries in Estonian schoolchildren aged 7 and 12 and to
      compare the findings with those of Danish children. DESIGN: Cross-sectional
      surveys in Estonia and Denmark, clinical oral examinations of children in 1997.
      SAMPLES AND METHODS: In Estonia, 195 children aged 7 and 215 children of age 12
      were selected in the municipality of Tartu in schools identified for oral health
      promotion projects. In Denmark, the study included 637 7-year-olds and 642 12
      year-olds living in the municipality of Horsens and served by the Public Dental
      Health Service for children. All children in the two countries were examined by
      calibrated dentists for dental caries according to the Recording System for the
      Danish Public Dental Health Service. RESULTS: At age 7, 83.8% of Estonian
      children had dental caries (7.7 dmfs) against 62.1% of Danish children (5.3
      dmfs). At age 12, the mean caries experience was 2.1 DMFS in Estonia against 1.3
      DMFS of the Danish children. Most of the caries indices were due to the high d/D
      components and approximal caries was prominent. In the study area in Estonia, the
      content of fluoride in drinking water was optimal (0.8-1.5 p.p.m.) whereas the
      level of fluoride was low in the Danish municipality (0.2 p.p.m.). CONCLUSION: In
      the Baltic states, the oral health systems are in transition. For the continuous
      improvement of oral health in childrens' reorientation of services should
      consider implementation of community-based oral health promotion and the schools
      provide an excellent setting for preventive oral care.

PMID- 11310241
TI  - Enamel hypomineralization of permanent first molars: a morphological study and
      survey of possible aetiological factors.
AB  - OBJECTIVES: The aim of this study was to investigate the morphological appearance
      of severe hypomineralized enamel of permanent first molars by means of polarized
      light microscopy, and to estimate the possible time, severity and longevity of
      the insult. Furthermore, the aim was to survey some commonly implicated
      aetiological factors in order to gain knowledge about possible pathogenesis of
      the enamel disturbances which could be compared with future epidemiological
      studies. SAMPLE AND METHODS: Seventy-three teeth, which had been extracted due to
      severe hypomineralizations of the enamel, were collected and serially cut
      longitudinally in a bucco-lingual direction. The sections were examined in
      polarized light, dry and embedded in water. The children were also examined with
      respect to the demarcated opacities of other permanent teeth than those that were
      extracted. The parents were asked about their health during the mother's
      pregnancy, the time of gestation, birth weight and any complications. They were
      also asked about the child's health during the first 2 years of its life, the
      length of time of breast-feeding and also about fluoride supplements. RESULTS:
      The hypomineralized areas extended cervically from the cusps, comprising about
      half of the buccal and lingual sides. The cervical borders to normal enamel were
      well defined and mainly followed the lines of Hunter-Schreger. The
      hypomineralized zones were covered by thin well-mineralized enamel. The majority
      of the children had demarcated opacities of all their first molars and also of
      some permanent incisors. No obvious correlation to the anamnestic data could be
      found. CONCLUSIONS: The hypomineralized enamel in the investigated teeth
      demonstrated areas of porosity of varying degrees. The yellow/brown defects were
      more porous than the white-cream and extended through the whole enamel layer,
      while the white-cream opacities were situated in the inner parts of the enamel.
      There had probably been an interacting disturbance of short duration of systemic
      origin of the activity of the ameloblast during the first 2 years of the child's
      life, resulting in chronological dispersed hypomineralized demarcated opacities
      in the developing teeth.

PMID- 11310242
TI  - 'Ilko dacowo:' canine enucleation and dental sequelae in Somali children.
AB  - OBJECTIVE: To assess the prevalence of primary canine enucleation and associated
      dental sequelae in Somali children resident in Sheffield. DESIGN: Cross-sectional
      survey. SETTING: Somali religious education classes and homework groups, selected
      primary and secondary schools, and the Charles Clifford Dental Hospital,
      Sheffield (1998-99). SUBJECTS AND METHODS: The target population were all Somali
      children aged between 4 and 17 years. Subjects were interviewed to obtain
      background sociodemographic data and an oral examination was performed. The
      status of the canine in each quadrant was noted, in addition to the presence of
      any dental anomalies in adjacent teeth. Features indicative of a history of
      attempted canine enucleation included: absence of primary canines, localized
      developmental defects affecting primary or permanent canines and lower lateral
      permanent incisors, and retention of lower primary lateral incisors with distal
      eruption of permanent lateral incisors. RESULTS: A total of 260 children were
      included in the study, comprising 56.5% of the target population. The mean age of
      the subjects was 9.7 years with an equal male and female distribution. According
      to the criteria devised, 82 (31.5%) of the subjects were considered to exhibit
      one or more of the dental features suggestive of a previous history of canine
      enucleation. There was no significant difference in prevalence according to
      gender or birthplace (UK, Somalia or another country), but a positive history was
      greater in subjects whose mother did not speak English. In addition to anomalies
      involving canines, lower permanent incisors were commonly missing (5.0% of
      children aged over 9 years). CONCLUSION: The suspected continuation of canine
      enucleation in UK-born Somali children raises important oral health issues.
      Culturally sensitive education is indicated to discourage this harmful ritual
      practice.

PMID- 11310244
TI  - Caries experience and streptococci and lactobacilli salivary levels in 6-8-year
      old Sardinians.
AB  - OBJECTIVES: The aim of this investigation was to compare clinical data regarding
      oral status (DMFT/DMFS indices) and streptococci or lactobacilli counts in
      stimulated whole saliva in two groups of children, aged 6 and 8 years. METHODS:
      Seventy-nine boys and 93 girls aged 6 (84 subjects) and 8 (88 subjects) years old
      were selected. DMFT/dmft, DMFS/dmfs and OHI-S indices were recorded. Mutans
      streptococci (Sm) and lactobacilli (Lb) salivary levels were assessed using
      commercially available strip tests and were rated from 0 to 3 and from 0 to 4 in
      the group as a whole. RESULTS: Mean dmfs was 9.06 +/- 10.80, made up of ds = 7.28
      +/- 9.54, fs = 1.19 +/- 3.64 and ms = 0.59 +/- 3.47. Mean DMFS was 0.73 +/- 1.91,
      made of DS = 0.54 +/- 1.29, FS = 0.08 +/- 0.56 and MS = 0.11 +/- 0.56.
      Statistically significant differences were found for both Sm and Lb scores
      between those with and without caries in the primary teeth (P < 0.05). The
      different Lb scores were also significant in relation to caries in permanent
      teeth in older children. CONCLUSION: A high proportion of children had some
      caries experience, and were in need of treatment.

PMID- 11310243
TI  - An investigation of the oral status and reported oral care of children with heart
      and heart-lung transplants.
AB  - AIM: To investigate the oral health status and oral microflora of children who
      have received heart and heart-lung transplants. Parental knowledge and current
      practice of oral health procedures by the child were also investigated. SAMPLE
      AND METHOD: Thirty-five children attending the Cardio-Thoracic Transplant Unit,
      Great Ormond Street Hospital for Children were included. Measurements were
      compared with children matched by age and gender attending the trauma clinic at
      the Department of Paediatric Dentistry, Eastman Dental Hospital. Teeth were
      examined for the presence or absence of caries or enamel defects. Plaque
      deposition, gingivitis, gingival bleeding and gingival enlargement were measured
      and a swab was taken to look at the oral microbial flora. A questionnaire was
      used to assess parental knowledge of dental health procedures and the current
      practice of these. RESULTS: There were no significant differences between
      transplant and control children in caries experience, plaque or gingivitis.
      Children with heart or heart-lung transplants had significantly greater numbers
      of enamel defects and more gingival enlargement than control children, children
      in the heart transplant group had significantly more gingival bleeding. There was
      little difference in the dental knowledge and reported behaviour of the
      transplant group compared to the control group. CONCLUSION: The dental needs of
      heart and heart-lung transplant patients treated at the Great Ormond Street
      Hospital for Children were similar to those of the control group in this study,
      however further improvement could be made in educating parents and children on
      the importance of caries prevention and good oral hygiene.

PMID- 11310245
TI  - Primary molar pulp therapy--histological evaluation of failure.
AB  - OBJECTIVES: Qualitative comparison of the clinical, radiographic and histological
      outcomes in a small sample of cariously exposed primary molars, extracted after
      unsuccessful pulp treatment by two vital pulpotomy methods. SUBJECTS AND METHODS:
      The primary molars were extracted, because of treatment failure, during a
      longitudinal clinical investigation of the relative efficacy of 20% Buckley's
      Formocresol versus calcium hydroxide powder as pulp dressings in vital pulp
      therapy (in press). Fifty-two child patients were sequentially enrolled in the
      longitudinal clinical investigation, 26 boys and 26 girls. Primary molar teeth
      requiring vital pulp therapy were randomly allocated to either the formocresol
      group (F) or the calcium hydroxide group (C). Coronal pulp amputation was
      prescribed only in teeth with vital, cariously-exposed pulp tissue. All cases
      were reviewed using predefined clinical and radiological criteria. Seventy-nine
      cariously-exposed primary molars required vital pulp therapy. Forty-four teeth
      were included in group F and 35 in group C. Five per cent (n = 2) of teeth in
      group F and 11 per cent of teeth (n = 4) in group C were terminated from the
      trial due to clinical and/or radiographic failure. Of the six teeth extracted,
      five were sufficiently intact to be retained for histological evaluation.
      RESULTS: Post-extraction radiographs taken before specimen preparation showed
      reactionary dentine barrier (bridge) formation in teeth treated with calcium
      hydroxide. However, the narrowing of root canals, indicative of appositional
      reactionary dentine deposition, was seen in both groups (F and C). Histological
      examination confirmed these findings and revealed that pus cells were evident in
      all specimens examined. There was also histological evidence of resorption of
      reactionary dentine within the root canal and that forming the calcified barrier
      (dentine bridge). CONCLUSION: The clinical and radiographic outcomes for the five
      teeth correlate well with the reported findings from decalcified histological
      section. Although numbers are small, the histological findings may indicate
      possible reasons for treatment failure. There are few reports of this sort in the
      literature of this under-researched treatment modality.

PMID- 11310246
TI  - Provision of dental care for medically compromised children in the UK by General
      Dental Practitioners.
AB  - The aim of this study was to investigate the views of General Dental
      Practitioners (GDPs) regarding their provision of dental treatment for medically
      compromised children. A questionnaire to assess confidence, experience and
      willingness to treat eight specific groups of medically compromised children was
      sent to 524 GDPs. Information is based on 271 completed questionnaires. The
      median number of children treated by GDPs in each of the eight groups over the
      previous 5 years was 0-2. Eighty percent of respondents stated that they would
      value further training in the provision of dental care for medically compromised
      children. Confidence was highest in providing dental treatment for children with
      three conditions: congenital heart disease (37% very confident), diabetes (39%
      very confident) and epilepsy (41% very confident). These were also the conditions
      that the GDPs reported as presenting most frequently in the dental surgery. GDPs
      reported least confidence in providing dental care for children with haemophilia
      (12% very confident) and organ transplants (14% very confident). Only 30% of GDPs
      wanted to be routinely involved with the provision of dental care for medically
      compromised children. The results indicate that medically compromised children
      may have problems accessing dental care and expertise. A system of integrated
      medical and specialised dental care is suggested.

PMID- 11310247
TI  - Dyskeratosis congenita: report of a case.
AB  - Dyskeratosis congenita is a rare multisystem condition involving mainly the
      ectoderm. It is characterized by a triad of reticular skin pigmentation, nail
      dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may
      also be present. Complications are a predisposition to malignancy and bone marrow
      involvement with pancytopenia. The case of a 14-year-old girl is described who
      presented with several of the characteristic systemic features of this condition,
      together with the following oral features: hypodontia, diminutive maxillary
      lateral incisors, delayed dental eruption, crowding in the maxillary premolar
      region, short roots, poor oral hygiene, gingival inflammation and bleeding,
      alveolar bone loss, caries and a smooth atrophic tongue with leukoplakia.
      Although this condition is rare, dental surgeons should be aware of the dental
      abnormalities that exist and the risk of malignant transformation within the
      areas of leukoplakia.

PMID- 11310248
TI  - Late forming supernumerary tooth in the premaxilla: a case report.
AB  - A case of late forming supernumerary tooth in the premaxilla is presented in this
      report. The patient has been followed-up radiographically from the age of 9 years
      but the supernumerary tooth could only be detected radiographically when the
      patient was 11 years old. This emphasises the importance of thorough clinical and
      radiographic examination of the developing dentition in children.

PMID- 11310249
TI  - Simultaneous occurrence of unusual odontodysplasia and oligodontia in the
      permanent dentition: report of a case.
AB  - Odontodysplasia is an uncommon clinicopathological condition with a variety of
      expressions. Although it is generally recognized as a localized disorder of
      dental tissue, its aetiology has not yet been well explained. In the present
      case, odontodysplasia with oligodontia in the permanent dentition is reported.
      The patient was in good health with normal stature and no other physical
      abnormalities. His parents and siblings were dentally and medically normal. The
      primary teeth appeared to be normal except for the primary second molars, where
      the enamel was malformed. However, the permanent incisors that had erupted into
      the oral cavity showed rough and hypoplastic enamel. An orthopantomogram showed
      17 congenitally missing permanent teeth and malformation of the other 11
      permanent teeth and tooth-germs. Because these findings were caused by
      developmental disturbances of both the mesodermal and ectodermal dental
      components, we diagnosed the present case as odontodysplasia accompanied by
      oligodontia in the permanent dentition.

PMID- 11310250
TI  - The management of severe dental phobia in an adolescent boy: a case report.
AB  - Dental fear is a widespread problem that represents one of the major barriers to
      dental care. This report describes a case study of a 12-year-old boy who
      presented with dental phobia characterized as 'fear of catastrophe', 'generalized
      dental fear' and 'fear of specific stimuli'. The referral came from his general
      dental practitioner who had been unable to carry out even the simplest dental
      procedure on him. The patient required prevention, conservation and root canal
      therapy. The case illustrates the use of physical strategies, including muscle
      relaxation and relaxation breathing; practice strategies, including graded
      exposure and cognitive strategies, combined with individual control methods and
      inhalation sedation to successfully complete the dental treatment plan.

PMID- 11310251
TI  - UK National Clinical Guidelines in Paediatric Dentistry. Diagnosis and prevention
      of dental erosion in children.

PMID- 11310252
TI  - Case of the month. Caught cold.

PMID- 11310253
TI  - Chest pressure discomfort & pain.

PMID- 11310254
TI  - Internal cardiac massage.

PMID- 11310255
TI  - Rate rescue. The diagnosis & treatment of bradycardic rhythms.

PMID- 11310256
TI  - Time is muscle. The Cape Cod Chest Pain Task Force helps shorten AMI discovery-to
      treatment times.

PMID- 11310257
TI  - Sac attack.
AB  - Although cardiac tamponade remains uncommon, morbidity and mortality from cardiac
      tamponade are high. EMS providers must understand the numerous causes and
      prehospital management of cardiac tamponade. Proper identification of its signs
      and symptoms, followed by correct management, may save lives.

PMID- 11310258
TI  - [Achieve success in your veterinary practice].

PMID- 11310259
TI  - [Use of antibiotics in humans and animals].

PMID- 11310260
TI  - [Vaccination, the end?].

PMID- 11310261
TI  - [Meeting of partners fertility improvement. First NRS-STO fertility award].

PMID- 11310262
TI  - [More research needed for BSE victims].

PMID- 11310263
TI  - [Overkill of rules must be logical and explanatory].

PMID- 11310264
TI  - [Keep secret or speak?].

PMID- 11310265
TI  - [Does the veterinary legal court open the door to the 'American way' in the
      Netherlands? Veterinarians pay up to 10,000 guilders in material and emotional
      damages?].

PMID- 11310266
TI  - [Euthanasia at night time?].

PMID- 11310267
TI  - [Busy meeting of GR and GKZ. Veterinarians want more information about BSE].

PMID- 11310268
TI  - [Chlamydia pneumoniae and cerebrovascular disease].
AB  - INTRODUCTION: Chlamydia pneumoniae has relationship with artherosclerosis of
      carotid artery by seroepidemiological studies and by demonstration of the
      bacteria in atheromata. We made a case-control study to know the seroprevalence
      of chronic infection of C. pneumoniae and the presence of the bacteria in
      arterial biopsies. PATIENTS AND METHODS: The cases group was constituted by 26
      patients undergoing carotid surgery. In the control group there were 50 patients
      without atherosclerosis and who underwent removal of their varicose veins. There
      were matched for sex, age and smoking. We obtained serum samples to determinate
      IgG antibodies against MOMP by MIF and ELISA. In the cases group, we got the
      arterial biopsies from carotid artery, and from pudendal arteries in control
      group. We determined chlamydial DNA on the biopsies by heminested PCR (primers:
      HL-1, HM-1, HR-1). We measured fibrinogen in both groups. RESULTS: By MIF
      technique, the seroprevalence was (IgG > 1:32) 69.23% cases versus 24% controls
      (OR: 7.12, CI: 2.47-20.48). The ELISA showed 76.92% of seropositivity in cases
      versus 16% in controls (OR: 17.5, CI: 95%: 5.35-57.23). The DNA of C. pneumoniae
      was found in 18 cases and 6 controls, (p < 0.0001, chi 2). We did not find any
      relationship between fibrinogen levels and groups. CONCLUSION: We think that
      there is a relationship between chronic infection with C. pneumoniae and carotid
      atherosclerosis.

PMID- 11310269
TI  - [Complications in the hemiplegic patient in the first year after the stroke].
AB  - INTRODUCTION: After a cerebrovascular accident (CVA) a hemiplegic patient is at
      risk from numerous complications after leaving hospital. OBJECTIVE: To analyze
      the frequency of occurrence of the commonest complications characteristic of the
      hemiplegic syndrome, during the first year after the stroke. PATIENTS AND
      METHODS: We evaluated 73 hemiplegic patients admitted to the rehabilitation
      department for treatment after a stroke. At each medical consultation, on
      admission and three, six and twelve months after the CVA, the complications
      'belonging' to the hemiplegic syndrome were evaluated. These included
      contractures, painful shoulder, sympathetic-reflex dystrophy, fractures and
      thalamic pain. RESULTS: During the first year of the illness 81% of the patients
      had some type of complication. A painful shoulder was the commonest complication,
      seen in 40% of the patients, followed by contractures (23%). Sympathetic-reflex
      dystrophy of the paretic arm occurred in 11 patients (15%). CONCLUSION: The
      commonest complication in patients during the first year after their stroke are
      painful shoulder and contractures.

PMID- 11310270
TI  - [Risk factors predictive of neurological sequelae in term newborn infants with
      perinatal asphyxia].
AB  - INTRODUCTION: Perinatal asphyxia (PA) and its neurologic manifestations are the
      most important cause of brain injury and neurologic sequelae in full-term
      infants. The objective of this study is to analyze the perinatal risk factors of
      neurologic sequelae in asphyctic term newborns. PATIENTS AND METHODS: One hundred
      and fifty-six consecutive asphyctic term infants were studied prospectively
      during 40 months. PA was graded in two stages (severe and non-severe), hypoxic
      ischemic encephalopathy classification was based on Levene's criteria, and
      neurologic sequelae was based on Finer and Amiel-Tisson's criteria. The perinatal
      variables were graded as prenatal (gestational and obstetrics), neonatal
      (resuscitation, general data of the newborn, and organic manifestations of
      asphyxia) and postneonatal (neurologic sequelae with at least 24 months of follow
      up). The relationships between these variables are studied by univariant and
      multivariant analysis (Cox's regression). RESULTS: PA was graded as severe in 31
      cases and non-severe in 125. Neurologic manifestations (hypoxic-ischemic
      encephalopathy) during neonatal period were present in 25.6%, and extraneurologic
      manifestations (hypoxic-ischemic disease) in 41.7% cases. The incidence of
      neurologic sequelae, in 115 asphyxiated full-term infants follow-up at least 24
      months, was 16.5% (19 cases). The perinatal variables associated to risk of
      neurologic sequelae on univariate analysis are variables of neonatal
      resuscitation (1 minute Apgar score < or = 4, 5 minute Apgar score < or = 6,
      endotracheal intubation, severity of PA) and variables of systemic manifestations
      (hypoxic-ischemic encephalopathy, cardiovascular and multi-systemic dysfunction,
      and mechanical ventilation). But only two variables are independently associated
      on multivariate analysis: severe PA (RR = 2.82; IC = 1.07-7.39) and hypoxic
      ischemic encephalopathy (RR = 4.17; IC = 1.48-11.75). CONCLUSIONS: The best
      predictive risk factors for the neurological prognosis at follow-up are severe PA
      at birth and/or evidence of encephalopathy in neonatal period.

PMID- 11310271
TI  - [Confirmation of the high prevalence of attention deficit disorder in a Colombian
      community].
AB  - INTRODUCTION: Using a shortened rating scale, the prevalence of Attention Deficit
      Hyperactivity Disorder (ADHD) has been reported to be very higher in a Colombian
      population. However, these data require clinical confirmation. OBJECTIVE: To
      confirm clinically the prevalence of ADHD in Colombian children and adolescents.
      PATIENTS AND METHODS: A randomized sample of 4 to 17 year old children and
      adolescents--184 males and 157 females--was selected from the schools. Sample was
      stratified in two socioeconomic status: high (4, 5, 6) and low (1, 2, 3). Several
      parents' and teachers' rating scales for the diagnosis of ADHD, standardized and
      validated in the Colombian population, were applied to the sample. The diagnosis
      of ADHD was confirmed using a semi-structured psychiatric and neurological
      interview, and medical histories revisions. RESULTS: Analysis found that
      prevalence of ADHD is 17.1%. Distribution for ADHD types was: combined 9.4%,
      inattentive 6.7% and hyperactive-impulsive 1%. Prevalence for boys was
      significant higher (21.8%) than for girls (10.9%) (chi 2 = 11.8, p < 0.01). In
      male predominate combined type and in female inattentive. Higher prevalence was
      found in low socioeconomic strata. Preschool children have lower prevalence
      (6.2%) than school 6 to 11 year old children (22.6%) and adolescents (21.6%).
      CONCLUSION: A higher prevalence of ADHD was confirmed in Colombian population.

PMID- 11310272
TI  - [Analysis of complex segregation in a large family with hereditary
      cerebrovascular disease in Antioquia, Colombia].
AB  - INTRODUCTION: Among different kinds of cerebrovascular diseases, few of them are
      caused by genetic disturbances, such as CADASIL (caused by Notch3 mutations),
      CARASIL, mitochondrial encephalopathy, MELAS and dementia typed Binswanger.
      However, to describe these type of cerebrovascular diseases related with genetic
      mutations could permit to determinate the causes of both hereditary and sporadic
      cerebrovascular diseases and then lead solutions. OBJECTIVE: To describe the
      genetic, environmental and cohort factors that determinate the presence of many
      affected people by a several cerebrovascular diseases in the pedigree of a large
      family from Antioquia (Colombia). PATIENTS AND METHODS: We performed one pedigree
      (268 individuals), through singular recruit and then complex segregation analysis
      with POINTER program. RESULTS: The model that more close to data is autosomal
      dominant mayor locus without influence of environmental factors. Frequency of
      allele of susceptibility to develop stroke or subcortical vascular dementia was
      0.0006. Mayor gene is over epistatic effects or interactions with other gene.
      CONCLUSIONS: Described an autosomal dominant hereditary model through complex
      segregation analysis in a pedigree of patients with hereditary cerebral vascular
      diseases characterized by recurrent strokes, early onset subcortical dementia,
      hearing loss, antecedent of migraine and MRI signal abnormalities, subcortical
      infarcts and leukoencephalopathy. In this family the parameter calculated,
      autosomal dominant model, and clinical feature strongly support the diagnostic of
      CADASIL, linkage analysis and sequentiation will be performed to determinate if
      mutant gene is Notch3.

PMID- 11310273
TI  - [Carotid-basilar artery communication in gerbils (Meriones unguiculatus)].
AB  - INTRODUCTION: Since 1966 when Levine and Payan observed that the Mongolian gerbil
      (Meriones unguiculatus) was unusually susceptible to cerebral infarction
      following occlusion of one or both common carotid arteries, the model has been
      used for the experimental study of cerebral ischemia. OBJECTIVE: To assess the
      presence of anterior-posterior arterial communication in the Mongolian gerbil
      (Meriones unguiculatus). MATERIAL AND METHODS: 26 animals were used and divided
      in the following groups: 1. Bilateral carotid ligation (n = 10); 2. Unilateral
      left carotid ligation (n = 5); 3. Unilateral carotid right carotid ligation (n =
      5); and 4. Control group without carotid ligation (n = 6). RESULTS: Postmortem
      intra-aortic dye injection demonstrated communication between anterior and
      posterior cerebral arteries in 30% of gerbils that previously were subjected to
      bilateral common carotid artery occlusion. A number of vessels, between 8.95
      11.35 microns in diameter, were linking the basilar artery with the posterior
      cerebral artery. In the remaining animals, the absence of communication was
      confirmed. CONCLUSION: Communicating carotid-basilar in lower number of cases and
      anastomosis the smallest diameter to give the gerbil advantage on others species
      as model of experimental regional ischemia.

PMID- 11310274
TI  - [High prevalence of ADDH: disturbed children or disordered society?].

PMID- 11310276
TI  - [Magnetic resonance spectroscopy and functional magnetic resonance images: non
      invasive alternatives for identifying epileptogenic foci].
AB  - Magnetic resonance spectroscopy and functional magnetic resonance images are new
      non-invasive techniques which have the potential for localization of the
      epileptogenic focus in patients with refractory focal epilepsy, who are
      candidates for surgery. Determination of patterns of asymmetry of the N-acetyl
      aspartic acid (NAA) between homologous regions of the temporal lobes, using
      magnetic resonance spectroscopy contributes to preoperative lateralization in
      patients with temporal lobe epilepsy. This technique may become a method for
      localization if its usefulness in the differentiation of mesial temporal lobe
      epilepsy from neocortical epilepsy is validated. Functional magnetic resonance
      images triggered by epileptiform discharges on the EEG, when combined with
      methods for localizing the source, permit the site of the epileptogenic focus to
      be found. This would particularly benefit patients with non-lesional extra
      temporal epilepsy who are potential candidates for invasive recordings. The use
      of magnetic resonance spectroscopy and functional magnetic resonance images in
      the preoperative evaluation of patients with refractory focal epilepsy,
      especially if it is used together with the relevant clinical data and that from
      other structural and functional imaging techniques, will reduce invasive
      monitoring and increase the accessibility to surgical treatment for this
      condition.

PMID- 11310275
TI  - [Chlamydia and arteriosclerosis: a few grey areas still remain].

PMID- 11310277
TI  - [Ring chromosome 20: an epileptic channel disorder?].
AB  - INTRODUCTION: The ring-shaped chromosome 20 (r20) syndrome is an infrequent
      chromosopathy which is associated with epileptic seizures, behaviour disorders
      and mental retardation. It results from the fusion of the two arms of the
      chromosome with deletion of the telomeric portions. CLINICAL CASE: We present a
      case of r20, review published cases and describe the clinical and
      neurophysiological characteristics. CONCLUSIONS: The r20 syndrome is the third
      type of epilepsy known to be of genetic basis related to chromosome 20. It has
      clinical and neurophysiological characteristics which give it a distinctive
      character and are easily identified. The fact that on locus 20q13 (telomeric
      portion of the long arm of chromosome 20) two genes related to epileptic
      channelopathies (CHRNA4 and KCNQ2) have been described, suggest the hypothesis
      that the subjacent deletion in cases of r20 syndrome affect one of these genes
      and explains the epileptogenicity. We consider this hypothesis and the
      possibility that r20 syndrome may be an epileptic channelopathy.

PMID- 11310278
TI  - [Acquired oculomotor paralysis in the adolescent].
AB  - INTRODUCTION: Acquired oculomotor palsy in juvenile age are most commonly due to
      head trauma, tumors, migraine, vasculopathies and demyelinating diseases.
      CLINICAL CASES: We document three cases of paroxysmal oculomotor nerve palsy in
      childhood, illustrating the main clinical symptoms, neurological examination, MR
      images, diagnosis, treatment and evolution. Final diagnosis were: multiple
      sclerosis, pineoblastoma, and craniopharyngioma. CONCLUSIONS: Sudden oculomotor
      nerve palsy occurring in youth in the absence of head trauma, viral infection or
      migraine access, firmly suggests a serious intracranial disease, and neuroimage
      studies should be quickly obtained to have an early diagnosis.

PMID- 11310279
TI  - [Mutism in children].
AB  - INTRODUCTION: Mutism is absence of verbal expression with conservation of
      language comprehension. The origin of mutism is multifactorial and may followed
      from cranial trauma surgery of the posterior fossa, acquired epileptic syndromes
      and psychogenic origin. OBJECTIVE: To refer patients who had presented mutism of
      diverse etiology. CLINICAL CASES: We analysed three children who had presented
      mutism originated by diverse causes. Case 1. A child with family and school
      problems, attention deficits and limited communication resources. Neurological
      examination and other auxiliary test (EEG) were normal. He presented no
      alteration in language or speech. We recommended the change of the school and a
      psychotherapeutic orientation. Case 2. A 4 year old female child who has suffered
      varicella 15 days earlier and presented limitations in her verbal expression
      despite maintain her linguistically capacity. She showed a indifferent behavior
      and her movements were without finality. Neurological examination was normal. The
      girl understood and followed instruction properly. However her verbal
      communication was absent. Total recuperation occurred in 72 hours. Case 3. A 12
      years old child who had suffered a cranial traumatism with loss of consciousness
      ten days earlier. After this traumatism, he presented behavior changes,
      disorientation and blurred vision. Additionally he presented stereotypies and
      limitations in psychosocial connections. Despite his mutism, he conserved the
      structure and content of language. SPECT showed hypoperfusion in orbitotemporal
      region. Improvement was total 20 days after his traumatism. CONCLUSIONS: The
      mutism has multifactorial etiology. References were made to three cases who's
      mutism was related to emotional causes, post-varicella complications and
      posttraumatic events.

PMID- 11310280
TI  - [Use of lamotrigine in the treatment of absence epilepsy crises].
AB  - OBJECTIVE: To review the current treatment and usefulness of lamotrigine in
      absence seizures. DEVELOPMENT: Absence seizures are classified amongst the
      generalized epilepsies. They are defined as a transient loss of consciousness of
      sudden onset and recovery characteristically associated with generalized spike
      and-wave discharges on the EEG. In recent years, the epileptic syndromes
      associated with this type of seizure have been better defined, basically by means
      of video-EEG studies. The International League Against Epilepsy has recognized
      four epileptic syndromes with typical absences: absence-epilepsy of childhood,
      juvenile absence-epilepsy, juvenile myoclonic epilepsy and epilepsy with
      myoclonic absences. The classical treatment for this type of seizure was based on
      ethosuximide, or more often, sodium valproate. Sometimes both drugs together were
      necessary. Other useful drugs are the benzodiazepines such as clobazam.
      CONCLUSIONS: We review studies of the efficacy and tolerance of lamotrigine in
      the treatment of absence seizures, one of the groups of seizures in which this
      drug has been shown to be most effective. Although studies comparing lamotrigine,
      valproate and ethosuximide are necessary, we emphasize the possibility that
      lamotrigine may be a drug of choice in absence seizures.

PMID- 11310281
TI  - [The P300 component of evoked potentials in the evaluation of schizophrenia: new
      evidence and future visions].
AB  - OBJECTIVE: To analyze the character as pathophysiological marker of the P300
      component in the evaluation of schizophrenic illness. We therefore review
      clinical and neuropsychological evidence of studies in which this was used as a
      tool for evaluation to reach a diagnosis. DEVELOPMENT: The P300 component is
      useful for studying not only cognitive processes but also the physiopathology of
      complex disorders such as schizophrenia. This component reflects the state of
      functions of attention control and memory, both necessary for final evaluation of
      a stimulus. These cognitive functions become altered in schizophrenic illness, as
      is shown by abnormality in the generation of the P300 component. We review the
      most relevant results, which permit characterization of the many features of
      schizophrenia from genetic, symptom, morphology and neuropsychological studies in
      which the P300 component is particularly relevant. Similarly, we analyze current
      controversies due to the great heterogeneity of methodology and the nature of the
      illness itself. CONCLUSIONS: Current understanding allows us to establish that
      the P300 is a biological marker of relevant aspects of schizophrenia such as the
      genetic risk of suffering a psychotic episode, determine the type and gravity of
      the symptoms of the disease, as well as the degree of structural deterioration of
      the patient. The P300 component is sensitive to the effect of different
      neuroleptic drugs, on both the symptoms and neuropsychological functions of the
      patient. These findings let us suggest the P300 component as a valid marker for
      the evaluation of schizophrenia and the neuropsychological processes.

PMID- 11310282
TI  - [Thrombolytics and neuroprotective agents in the treatment of the patient with an
      acute cerebrovascular ischemic accident].
AB  - INTRODUCTION: Cerebrovascular disease occupies second place amongst the causes of
      mortality in the world. Rapidly after onset of an acute ischemic cerebrovascular
      accident (CVA) there is irreversible formation of an area affected by the
      ischemic process (necrotic centre) surrounded by a zone in which reduction of
      blood flow is less marked. Although the neurons of this region, known as the
      'ischemic penumbra', are in a state of 'electrical silence', they may recover if
      effective treatment is started in time. DEVELOPMENT: Treatment of the patient
      with an acute ischemic CVA should be concentrated in two areas: restoration of
      blood flow and neuroprotection. In spite of better understanding of the
      biochemical, genetic and molecular processes which occur during the process of
      cerebral ischemia, the development of neuroprotector strategies has been largely
      fruitless. However, restoration of cerebral blood flow is currently possible in a
      certain group of patients. The fibrinolytic system is formed by an inactive
      proenzyme, plasminogen, which may be converted to the active form, plasmin, in
      the presence of specific activators such as tissue plasminogen activator (t-PA)
      and urokinase-type plasminogen activator (u-PA). CONCLUSIONS: The effect of
      thrombolytic treatment is due to dissolution of the fibrin present in the
      occluding thrombus, with subsequent restoration of the blood flow to the ischemic
      area. Nevertheless the use of thrombolytic agents has dramatically changed the
      clinical management of patients with acute ischemic cerebrovascular incidents.
      Their use involves a significant risk of intracerebral bleeding, which together
      with the narrow therapeutic window, has made this one of the most controversial
      fields of current neurology.

PMID- 11310283
TI  - [Endarterectomy and carotid angioplasty: surgical perspective].
AB  - INTRODUCTION: Carotid endarterectomy (CE) is a well-established operation,
      although recently it has been challenged by newer, less invasive procedures such
      as carotid angioplasty with or without insertion of a stent. DEVELOPMENT: In this
      article the author gives his views on the use of CE in patients with carotid
      stenosis, both those with and those without symptoms, and also those in whom no
      definite indication has yet been established. In symptomatic carotid stenosis it
      had been clearly shown that CE is an effective procedure for the prevention of
      strokes and death from strokes in patients with carotid stenosis of over 70%,
      provided that the patients have reasonable general health and life expectation.
      There is only minor benefit from surgery in patients with asymptomatic disease of
      the carotid arteries and much less than in those with symptomatic carotid
      disease. Therefore endarterectomy is recommended when there is obvious
      progression of the degree of stenosis, especially when the stenosis has reached
      70% or the patient begins to complain of symptoms. One of the most serious
      complications of CE is acute myocardial infarction. CONCLUSION: It is a good time
      to design careful randomised studies to compare endarterectomy with angioplasty,
      probably with stenting, in a selected group of patients at greater risk than
      those accepted for endarterectomy.

PMID- 11310284
TI  - [Angioplasty and stenting in carotid stenosis. Therapeutic alternative or
      technical possibility?].
AB  - OBJECTIVE: Review the current knowledge on the use of angioplasty and stenting
      (A/S) for the treatment of carotid stenosis with emphasis on proposed
      indications. DEVELOPMENT: The standard treatment for carotid stenosis is carotid
      endarterectomy (CE). However, excessive surgical risk and/or technical difficulty
      occasionally impose limitations on the surgical approach. Therefore, the option
      of percutaneous treatment with A/S becomes an appealing alternative. A/S
      techniques are constantly improved but there is very little prospective data
      supporting its value at present. The reported complication rates appear
      comparable to those of CE. Indications for A/S of the carotid artery are not
      fully delineated yet. We believe that adequate candidates for carotid A/S must
      have symptomatic high-degree carotid stenosis and at least one of the following
      situations: unstable coronary disease, severe systemic disease, surgically
      inaccessible carotid lesion (including some cases of carotid stenosis secondary
      to neck radiation), contralateral carotid occlusion, or recurrent stenosis after
      prior CE. CONCLUSIONS: A/S represents a promising alternative to CE in the
      treatment of carotid stenosis. However, in the absence of prospective comparative
      trials, A/S should be currently reserved exclusively for those patients in whom
      surgery is prohibited by very high surgical risk or technical inaccessibility.
      A/S of the carotid artery should only be performed by operators with ample
      expertise in the field.

PMID- 11310286
TI  - [Restless leg syndrome. Diagnosis and treatment].
AB  - INTRODUCTION: The restless legs syndrome is characterized by an unpleasant
      sensation in the legs which causes an imperative need to move the legs and is
      therefore considered to be a disorder of movement. When it appears before going
      to sleep, it may interfere with falling asleep and lead to a sleep-deficit.
      DEVELOPMENT AND CONCLUSIONS: It is a clinical condition with a satisfactory
      treatment, and improvement of the associated sleep disorder. The etiology is
      unknown, sometimes it is familial. The syndrome is increasingly often diagnosed,
      particularly in association with iron deficiency, during pregnancy, in chronic
      renal failure and in patients with peripheral neuropathy. Polysomnography is not
      necessary, unless one suspects an associated disorder of periodic leg movements.
      Treatment is by dopaminergic, opiate, benzodiazepine, anticonvulsant drugs or
      clonidine.

PMID- 11310285
TI  - [Treatment of acute brain edema].
AB  - OBJECTIVE: To review the basic concepts and mechanisms of cerebral edema and to
      analyze current management of this complex clinical problem. DEVELOPMENT:
      Cerebral edema is a stereotyped reaction of the brain to any aggression and is a
      very common complication in patients with alterations of the blood-brain barrier.
      The cerebral edema should be recognized and treated early and aggressively to
      avoid disastrous results such as cerebral herniation. The most important types of
      edema are the vasogenic and cytotoxic. The first implies primary alterations of
      the blood-brain barrier, whilst in the second they are of cellular homeostasis.
      We have reviewed how various pro-inflammatory substances interact to stimulate
      the mechanisms causing edema, and also the importance of cerebrovascular
      autoregulation for maintenance of a normal intracranial volume. The measures
      necessary for good cerebral reanimation are the following: evaluation of the
      airway, controlled hyperventilation, maintenance of the cerebral perfusion
      pressure > 70 mmHg, suitable position of the head, administration of hypertonic
      solutions, dexamethasone, and possibly barbiturates. We have shown that a body
      temperature > 37.5 degrees C and blood glucose > 150 mg/dl are related to
      worsening of the cerebral edema. Finally, we have reviewed other experimental
      treatments which seem promising, such as hemicraniectomy, hypertonic saline
      solutions, hypothermia and other neuroprotector agents. CONCLUSIONS: All patients
      with acute cerebral edema should be evaluated early and treated with therapy
      which will solve the underlying pathological problem. Good medical management of
      these patients is of vital importance to assure a satisfactory clinical outcome.
      Recently new, effective therapy has been evaluated which may substantially change
      current concepts of the treatment of patients with acute cerebral edema.

PMID- 11310287
TI  - [Neuroimaging in multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis is currently considered to be a destructive
      disorder, and a certain degree of alteration in immunity is considered to occur
      in genetically susceptible persons. DEVELOPMENT: Magnetic resonance (MR) has
      become the basic technique for diagnosis and evaluation of the response to
      treatment. The key factor in the information obtained form MR images is the water
      content. There are several technical situations to be taken into account when
      using MR in multiple sclerosis: phase T1, phase T2, FLAIR, phase T1 with
      gadolinium, MR with spectroscopy, cerebral parenchymatous fraction and
      magnetization transfer MR. Apart from magnetic resonance, immunological changes
      of multiple sclerosis are seen in the CSF in over 50% of the patients with the
      disorder. Use of evoked potentials, with the important advantage of detecting
      lesions not visible on MR and asymptomatic lesions, may also be useful for
      establishment of the diagnosis. CONCLUSION: In this article we describe the use
      of neuroimaging in the diagnosis of multiple sclerosis.

PMID- 11310288
TI  - [Pharmacologic treatment of multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is probably caused by many pathological
      factors, both intrinsic and extrinsic. DEVELOPMENT: When we consider the
      aetiology of MS, we have to take three basic factors into account: 1.
      Immunological factors: evidence of involvement of the immune system has been
      found in plasma, tissues and CSF; 2. Viral factors: epidemiological studies
      suggest that MS may be a result of contact with environmental factors during
      childhood or adolescence, and 3. Genetic factors although there is no evidence
      that MS is inherited directly, there is between 12 and 15 times more involvement
      of persons from affected families than from the general population. Regarding
      treatment, since this is a polysymptomatic disorder, the specialist should choose
      the most suitable drug or intervention in each case, according to the alterations
      which affect quality of life or the severity of the presenting symptom. Three
      pharmacological treatments are emphasized: steroids, immunomodulation and
      immunosuppression. CONCLUSION: In this article we review the aetiology of MS and
      its pharmacological treatment.

PMID- 11310289
TI  - [Management of closed head injury].
AB  - OBJECTIVE: To review current concepts regarding the management of severe closed
      head injury and determine the possible causes of brain damage in these patients.
      DEVELOPMENT: Severe closed head injury causes a high rate of mortality and
      disability in developed countries. The diagnosis and management of these patients
      has progressed in recent years, from the availability of brain scanning to varied
      therapeutic methods based on brain metabolism and intracranial dynamics. We have
      reviewed the different neuropathological processes in relation to closed head
      injury and emphasized the importance of recognition and control of the secondary
      lesions, which may have disastrous consequences for the patient. After clinical
      evaluation and early cardiorespiratory stabilization, the patients are taken to a
      critical care unit for continuous monitoring of the intracranial pressure,
      cerebral perfusion pressure and cerebral extraction of oxygen. We have discussed
      several therapeutic interventions taking into account the values obtained by
      continuous monitoring of these patients. As well as traditional measures
      (hyperventilation, manitol and barbiturate coma), there are other possibilities
      for treatment of these patients such as hypothermia, hypertonic saline solutions
      and neuroprotector agents. CONCLUSIONS: All patients with closed head injuries
      should be evaluated and treated as emergencies, and admitted to a critical care
      unit to avoid secondary lesions such as hypoxemia, arterial hypotension and
      cerebral edema. Treatment should be aimed at maintenance of the intracranial
      pressure and cerebral perfusion within normal limits and also maintenance
      satisfactory jugular saturation.

PMID- 11310290
TI  - [Brainstem pseudotumor imaging: atypical manifestation of multiple sclerosis in
      childhood].

PMID- 11310291
TI  - [Acute encephalopathy with myoclonus caused by phenytoin. Apropos of a case].

PMID- 11310292
TI  - [Iatrogenic neuropathy of cranial nerve XI or the accessory nerve].

PMID- 11310293
TI  - Permanent single chamber atrial pacing is obsolete.

PMID- 11310294
TI  - Is AAI or AAIR still a viable mode of pacing?

PMID- 11310296
TI  - Changes in quality-of-life after pacemaker implantation: responsiveness of the
      Aquarel questionnaire.
AB  - Before being introduced for widespread use, health status instruments should be
      evaluated for reliability, validity, and responsiveness to relevant clinical
      changes. In a previous study the validity and reliability of Aquarel, a disease
      specific quality-of-life (QOL) questionnaire for pacemaker patients, were tested
      and found satisfactory. The purpose of this study was to assess the sensitivity
      to change in health of Aquarel. A cohort of 51 patients was assessed at baseline
      and at 4-6 weeks after pacemaker implantation. We compared the sensitivity to
      change over time on the Aquarel scores to the scores on the SF-36 using various
      techniques (t-test value, effect size, standard error of measurement). Using the
      1-standard error of measurement (SEM) criterion for clinically relevant change,
      Aquarel seemed to provide better classification of patients compared to the SF-36
      alone. This study supports the value of Aquarel as a disease-specific measure of
      QOL in pacemaker patients.

PMID- 11310295
TI  - Ancillary tools in pacemaker and defibrillator lead extraction using a novel lead
      removal system.
AB  - A previous report described our preliminary experience with a highly successful
      pacing lead removal system (VasoExtor). Extending this experience, we found it
      necessary to use additional tools to enhance the success of percutaneous lead
      extraction with this system. In the present series, we used the standard locking
      stylets (S and K), and recently, one newer type of stylet (Magic) over the last 3
      years in 34 patients to extract 48 pacemaker leads in 31 patients and 3
      defibrillator (ICD) leads in 3 patients. Lead extraction was carried out in 23
      men and 11 women (aged 64 +/- 17 years) because of pacemaker infection (n = 21),
      pacemaker (n = 8) or ICD (n = 3) lead malfunction, or prior to ICD implant (n =
      2). Leads were in place for 3.5 +/- 3.7 years. Infections, involving pocket and
      lead(s), were due to S. epidermidis (n = 13), S. aureus (n = 6), S. aureus plus
      E. coli (n = 1), for fungi (n = 1). Of the 48 pacing leads, 31 were ventricular,
      15 atrial, and 2 were VDD leads. The ICD leads were two double-coil leads (CPI)
      and one single-coil lead (Telectronics). Using the S (n = 12), K (n = 8), or
      Magic (n = 3) stylets, all pacing leads in 23 patients and the ICD leads in 2
      patients were successfully removed from a subclavian approach using the locking
      stylets. However, in nine (26.5%) patients ancillary tools were required. In four
      patients, lead fragments were captured with use of a noose catheter, a pigtail
      catheter, and a bioptome from a right femoral approach. In two patients, locking
      could not be effected and a noose catheter from the right femoral vein was used,
      aided by a pigtail and an Amplatz catheter and a bioptome to remove three leads.
      In a patient with an ICD lead, a combined subclavian (stylet S) and right femoral
      approach (noose catheter) was required. In a patient with a dysfunctional
      ventricular lead 12 years old, a motor drive unit was used to facilitate the
      exchange of locking stylets, but extraction failed. In another patient, a
      fragment of a dysfunctional ventricular lead remained intravascularly despite
      resorting to a femoral approach. Finally, lead removal was completely (32/34,
      94%) or partially (1/34, 3%) successful in 33 (97%) of 34 patients for 50 (98%)
      of 51 leads without complications. In conclusion, to enhance the success of
      pacing or ICD lead extraction with use of the VascoExtor locking stylets, an
      array of ancillary tools were required in more than one fourth of patients.

PMID- 11310297
TI  - Psychological and physiological factors associated with tilt table testing for
      neurally mediated syncopal syndromes.
AB  - This study investigated psychological and physiological factors in two groups of
      patients who had tilt table testing for autonomic dysfunction. The first group of
      61 patients completed assessments of depression, anxiety, and symptom effects on
      lifestyle. The 25 patients identified as tilt positive were younger (30.5 years)
      and had higher mean depression scores (7.6) compared to the tilt-negative
      response group (n = 36); the latter averaged 40 years of age and had mean
      depression scores of 4.6. These differences were statistically significant. Women
      testing tilt positive were significantly more depressed than tilt-negative women
      (P = 0.02). More severe depressive symptoms were associated with lower blood
      pressure (BP) (P < 0.05). A second group of 52 patients was monitored during tilt
      for BP, heart rate (HR), skin temperature (TEMP), skin conductance level (SCL),
      and forehead muscle tension (EMG). Twenty-seven tested positive and 23 were
      negative. There were statistically significant group differences in systolic BP
      and diastolic BP (P < 0.05). There was a significant interaction between tilt
      status (positive or negative) and time (P = 0.03) in HR. TEMP increased 2 degrees
      over time in both groups (P < 0.05). The decrease in SCL from 13.7 to 10.4 mu
      omega in the tilt-positive response group compared to the slight increase in the
      tilt-negative group was significantly different (P < 0.05). Identification of
      psychological factors correlated with BP and physiological changes that accompany
      decreases in BP in tilt-positive response patients could guide management of
      patients with autonomic dysfunction.

PMID- 11310298
TI  - Effect of restoration of AV synchrony on stroke volume, exercise capacity, and
      quality-of-life: can we predict the beneficial effect of a pacemaker upgrade?
AB  - The aim of this study was to assess to what extent patients with VVIR pacemakers
      and without overt symptoms of a pacemaker syndrome benefit from a pacemaker
      upgrade, and if a preoperative noninvasive measurement of the change in stroke
      volume (SV) could predict the effect of a pacemaker upgrade. The study group
      consisted of 20 (12 women, 8 men) VVIR patients with a mean age of 60 years. The
      indication for the first implantation was AV block in 13 patients and SSS in 7.
      The mean time of a ventricular pacing was 77 months. The objective
      (echocardiography, an exercise capacity) and the subjective (the quality-of-life)
      parameters investigated in patients during ventricular pacing were compared to
      results obtained 2 months and 1 year after a pacemaker upgrade. To assess
      preoperatively a change in a SV expected after upgrading, attempts were made to
      restore AV synchronization by the use of a transesophageal pacemaker. An increase
      in SV (from 5% to > 35%) during temporary AV resynchronization was observed in
      each patient. Values of SV increase correlated with those obtained 2 months (r =
      0.65; P < 0.01) and 1 year (r = 0.66; P < 0.01) after an upgrade. Superior
      hemodynamics was associated with a significant improvement of an exercise
      capacity in both subgroups of patients. The most significant improvement in the
      quality-of-life was observed in patients with SSS. We did not find correlations
      between SV and the quality-of-life assessed 2 months (r = 0.043; NS) or 1 year (r
      = 0.02; NS) after an upgrade. In conclusion, a pacemaker upgrade performed after
      a long-term ventricular pacing resulted almost consistently in the improvement of
      hemodynamics and was associated with an increase of exercise capacity. In
      patients with SSS it was followed by the significant improvement of their quality
      of-life. Such a relation was not observed in patients with AV block as some of
      them (especially those with VVIR pacemakers) felt quite well during ventricular
      pacing. The proposed preoperative echocardiographic evaluation may precisely
      predict the degree of hemodynamic improvement expected after a pacemaker upgrade.

PMID- 11310299
TI  - Paradoxical undersensing at a high sensitivity in dual chamber pacemakers.
AB  - In view of the evolving indications for device therapy in atrial arrhythmia the
      accurate detection of high rate atrial events is a necessity. In a sheep model of
      atrial fibrillation (AF) we observed a contradictory behavior of the Thera DR
      pacemaker. The pacemakers were programmed to deliver burst pacing on detection of
      sinus rhythm (SR). Paradoxically, progressively more inappropriate bursts were
      delivered during AF, at a higher sensitivity. This implied that the pacemaker
      interpreted AF as SR. We assessed the atrial detection of the Thera DR, Diamond,
      Saphir, and Marathon pacemakers during AF, in a sheep model and in vitro using a
      waveform generator. By counting the annotated atrial-sensed events reported by
      the pacemaker we charted the behavior of the pacemakers at different
      sensitivities. At a higher sensitivity both the Thera DR and the Diamond
      paradoxically reported fewer atrial events during AF. This behavior led to
      inappropriate mode switching and incorrect diagnostic data collection. It could
      be reproduced in vitro. The Marathon did not show this paradoxical undersensing
      in vivo or in vitro. This paradoxical undersensing at a high sensitivity is
      dependent on the amplitude of the input signal and could not be explained by an
      overlap of programmable timing parameters. It is caused by ringing of the atrial
      sensing amplifier. At high atrial rates and a high sensitivity the ringing of the
      repetitive atrial signal input results in blanking of the atrial amplifier. This
      observation may be relevant in the device management of patients with paroxysmal
      AF.

PMID- 11310300
TI  - The effect of the atrial pacing site on the total atrial activation time.
AB  - The effect of dual site pacing for prevention of atrial fibrillation may be due
      to synchronization of right and left atrial activation. Little is known, however,
      about the effect of pacing from single right atrial sites on differences in
      interatrial conduction. Twenty-eight patients without structural heart disease
      were studied following radiofrequency catheter ablation of supraventricular
      arrhythmias. Pacing was performed using standard multipolar catheters from the
      presumed insertion site of Bachmann's bundle, the coronary sinus ostium, the high
      lateral right atrium, and the right atrial appendage (n = 8 patients). Bipolar
      recording was performed from the distal coronary sinus, the high and low lateral
      right atrium, and the posterolateral left atrium (n = 13 patients). The longest
      conduction time from each pacing to each recording site was considered the total
      atrial activation time for the respective pacing site. During high right atrial
      pacing, the total atrial activation time was determined by the conduction to the
      distal coronary sinus (118 +/- 18 ms), during coronary sinus ostium pacing by the
      conduction to the high right atrium (94 +/- 18 ms), and during Bachmann's bundle
      pacing by the conduction to the distal coronary sinus (74 +/- 18 ms). The total
      atrial activation time was significantly shorter during pacing from Bachmann's
      bundle, as compared to pacing from other right atrial sites. Thus, in normal
      atria, pacing from the insertion of Bachmann's bundle causes a shorter total
      atrial activation time and less interatrial conduction delay, as compared to
      pacing from other right atrial sites. These findings may have implications for
      alternative pacing sites for prevention of atrial fibrillation.

PMID- 11310301
TI  - Effect of ischemic stroke on the dynamic beat-to-beat QT-RR relationship.
AB  - The ECGs of 26 patients following ischemic stroke and 18 control patients with
      various orthopedic problems, all without primary heart disease, were examined to
      characterize the dynamic behavior of uncorrected QT interval in relation to
      changing RR interval during physiotherapy effort. ECG waveforms were analyzed to
      extract beat-to-beat QT and RR intervals. Based on performing multiple cross
      correlations, the relationship between the RR and QT intervals was calculated
      using the following general formula QTi = c RRib-1. Linear regression was
      performed on the logarithms of QT and RR measurements to estimate the constant (a
      = log c) and the slope (b) values, reflecting the dynamic change of QT during
      physiotherapy effort. Having these two values, the dynamic QT extrapolated to a
      heart period of 1 second (QTcd) was calculated. It was found that the mean slope
      (b) of the linear regression line in the ischemic stroke group was significantly
      lower than in the control group (0.26 +/- 0.08 vs 0.33 +/- 0.08, P < 0.02), and
      the constant (a) was significantly higher (1.83 +/- 0.21 for the ischemic stroke
      vs 1.61 +/- 0.23 for the controls, P < 0.002). No significant difference was
      found in QTcd values between the two groups (386 +/- 27 ms for the ischemic
      stroke vs 392 +/- 25 ms for the controls, P > 0.05). In conclusion, hemispheric
      brain infarction seems to result in alteration in the autonomic activity during
      exercise manifesting itself as distorted dynamic behavior of the QT interval.

PMID- 11310302
TI  - Laser extraction of entrapped leads.
AB  - Removing entrapped pacing and defibrillator leads has been greatly simplified by
      making use of the excimer laser extractor. Sixty-two leads were successfully
      removed, although where appropriate, portions of the lead remained in place in 10
      cases. There were two serious complications, one tear of the superior vena cava
      during an ICD extraction and one tear of the atrium during an atrial lead
      extraction. Both were controlled successfully through emergency sternotomy.
      Although extracting entrapped leads has been much simplified by making use of the
      laser extractor, the process is not free of serious complications. Those involved
      in explanting leads should be aware of the outcomes and be prepared for emergent
      management.

PMID- 11310303
TI  - The role of Purkinje and pre-Purkinje potentials in the reentrant circuit of
      verapamil-sensitive idiopathic LV tachycardia.
AB  - Although the mechanism of verapamil-sensitive idiopathic left ventricular
      tachycardia (ILVT) is usually reentry, the actual reentrant circuit is not
      clearly understood. This study examined the relationship between the Purkinje
      potential (PP) and a dull potential preceding PP (pre-PP) during ILVT to
      elucidate the roles of these potentials in the reentrant circuit of ILVT.
      Electrophysiological studies and radiofrequency catheter ablation were performed
      in ten patients (7 men, 3 women, mean age 29 years) who had an ILVT with a right
      bundle branch block configuration and left-axis deviation. Left ventricular
      endocardial mapping using an octapolar catheter and entrainment and resetting
      studies during VT was performed by pacing from the right ventricular outflow
      tract (RVOT) and each site of the left ventricular mapping catheter. PP and pre
      PP were recorded simultaneously during VT in all patients. The earliest PP during
      VT was recorded at the inferoposterior septum, and PP was activated
      bidirectionally toward the proximal (basal) and distal (apical) sites along the
      left posterior fascicle. In contrast, pre-PP was recorded at sites slightly
      proximal to the earliest PP recording site, and was activated toward the earliest
      PP site. Pacing from RVOT confirmed manifest entrainment, and the stimulus to pre
      PP interval was prolonged with a shorter pacing cycle length. Concealed
      entrainment was demonstrated by capture of the PPs of the left ventricular
      mapping catheter in six patients, and the postpacing interval at each PP site was
      equal to the tachycardia cycle length. The pre-PP was orthodromically activated
      from the proximal to the distal site during pacing. More rapid pacing also
      produced delay in activation from PP to pre-PP, indicating slow conduction in
      ILVT. Catheter ablation was performed at the pre-PP recording site during VT, and
      was successful in all patients. The reentrant circuit of ILVT could be
      constructed based on the pre-PP, PP, and slow conduction between the PP and pre
      PP. Catheter ablation of ILVT was successful at the pre-PP recording site.

PMID- 11310304
TI  - Antitachycardia pacing for rapid VT during ICD charging: a method to prevent ICD
      shocks.
AB  - In patients with ICDs, rapid VTs are usually treated with shocks. It is unknown,
      if antitachycardia pacing (ATP) delivered once for rapid VT during capacitor
      charging can avoid painful shocks without increasing the risk of syncope. In
      patients in whom rapid monomorphic VT (cycle length 300-220 ms) could be
      reproducibly induced during predischarge ICD testing, the success of
      cardioversion (defibrillation threshold plus 10 J) and a single ATP attempt
      (burst with 8 or 16 stimuli) was compared using a randomized crossover study
      design. Consciousness of the patients was checked by the signal from a button
      constantly pushed by the patient. In 20 patients (ejection fraction 0.50 +/-
      0.19) rapid VTs (253 +/- 26 ms) were reproducibly induced. A single burst
      successfully terminated 11 (55%) of 20 rapid VTs, 6 episodes could not be
      terminated with a single burst pacing and 3 VTs accelerated. Rapid VTs not
      terminated by ATP were significantly faster than those that could be terminated
      (246 vs 258 ms, P = 0.026). Cardioversion (19 +/- 3 J) terminated the VTs in all
      cases. No patient suffered syncope during rapid VTs. A single ATP may terminate
      rapid VT with cycle lengths < 300 ms in 55% of patients without increasing the
      risk of syncope. Therefore, in rapid VTs one attempt of ATP may be suitable as an
      additional therapy option during ICD capacitor charging to avoid painful shocks
      without compromise of safety. Thus, future ICDs should implement the option of
      ATP during charging of capacitors.

PMID- 11310305
TI  - QT interval dispersion in ventricular beats: a noninvasive marker of
      susceptibility to sustained ventricular arrhythmias.
AB  - Increased QT dispersion (QTd) calculated from sinus beats has been shown to
      identify patients prone to sustained VT. However, predictive accuracy of this
      parameter is limited. Electrophysiological properties of the myocardium may be
      altered by a premature ventricular beats, which is a well-established trigger for
      sustained VT. Therefore, the author hypothesised that QTd in spontaneous or paced
      ventricular beats may improve identification of patients with inducible sustained
      VT. In 28 consecutive patients (men, mean age 61 +/- 13 years) who underwent
      programmed ventricular stimulation, the values of QTd calculated in sinus and
      ventricular beats were compared between inducible and noninducible patients. The
      mean QTd values obtained using three different methods differed significantly,
      QTd in paced ventricular beats being the highest, QTd in spontaneous ventricular
      beats was intermediate, and QTd in sinus beats was the lowest (83.9 +/- 30 vs
      63.0 +/- 29 ms vs 53.9 +/- 27 ms, P < 0.0001 and P < 0.004, respectively). In 13
      (46%) patients sustained VT was induced. QTd values were significantly higher in
      inducible than noninducible patients (QTd sinus beats: 67.5 +/- 31 vs 42.1 +/- 11
      ms, P = 0.02; QTd spontaneous ventricular beats: 79.3 +/- 35 vs 46.7 +/- 13 ms, P
      = 0.008, and QTd-paced ventricular beats: 104.8 +/- 32 vs 65.9 +/- 9 ms, P =
      0.0009). The receiver operator characteristic curves showed that at a sensitivity
      level of 100%, the highest specificity for identification of inducible patients
      had QTd measured in paced ventricular beats (87%) followed by QTd in spontaneous
      ventricular beats (45%), and QTd in sinus beats (40%). In conclusion, (1) QTd in
      ventricular beats is greater than in sinus beats, and (2) QTd calculated from
      paced ventricular beats identifies patients with inducible sustained VT better
      than QTd measured during sinus rhythm.

PMID- 11310307
TI  - The impact of QT lag compensation on dynamic assessment of ventricular
      repolarization: reproducibility and the impact of lead selection.
AB  - In cardiac disease, abnormalities exist in the rate-corrected QT interval and the
      relationship between QT and heart rate. The QT/RR relationship is known to be
      dynamic and show circadian variation. The availability of automated methods for
      measurement of QT and RR intervals allows monitoring of the QT/RR relationship
      and may provide insights into arrhythmia onset. Using a method for analyzing 24
      hour recordings that incorporates beat-by-beat QT and RR measurement and an
      automated mechanism for compensating for lag in adaptation of QT to changes in
      RR, the authors evaluated the impact of lag compensation on assessment of the
      QT/RR relationship, reproducibility, and the effect of lead selection in 15
      normal subjects. The QT/RR relationship is continuously estimated from the lag
      compensated data over a 5-minute scrolling time frame. The relationship is
      expressed as an exponential formula, QT = QTo.RRJ where QTo is the QT interval at
      a standardized RR interval of 1 second and J is a variable exponent. We found
      that the use of lag compensation significantly improves the mean 24-hour
      correlation between QT and RR data (r = 0.87 vs 0.65). The 24-hour mean of QTo
      and J were highly reproducible (coefficients of variation 2% and 8%,
      respectively). The mean 24-hour QT/RR relationship for the population was QT =
      0.415.(RR)0.32. There was a small difference between leads in QTo and J.
      Compensating for QT adaptation lag provides a means of assessing the QT/RR
      relationship over long and short periods. This method allows investigation of the
      effect of acute interventions on the dynamic QT/RR relationship, which has
      previously been restricted by the presence of QT hysteresis.

PMID- 11310306
TI  - AV block and changes in pacing mode during long-term follow-up of 399 consecutive
      patients with sick sinus syndrome treated with an AAI/AAIR pacemaker.
AB  - This retrospective study included a large cohort of consecutive patients
      primarily implanted at Skejby University Hospital with an AAI/AAIR pacemaker
      because of sick sinus syndrome (SSS) from July 1981 to July 1999. The primary aim
      of the study was to analyze the risk of developing AV block during long-term
      follow-up. A secondary aim was to study the incidence and reasons for changes in
      pacing mode caused by other than AV block. A total of 399 patients (231 women,
      mean age 71 +/- 13.5 years) were identified. Mean follow-up was 4.6 +/- 3.4 years
      and occurred at death, reoperation with mode change, pacemaker explant, or end of
      study. During follow-up, 44 patients had a ventricular lead implanted with a mean
      delay of 2.8 +/- 3.1 years (range 1 day-10.4 years) after the primary
      implantation. A total of 30 patients received a ventricular lead because of AV
      block or AF with bradycardia (annual incidence 1.7%). Another 14 patients
      received a ventricular lead without having documented AV block or AF with pauses
      (annual incidence 0.8%). The present observational study documents that in
      patients with SSS treated with AAI/AAIR pacing, AV block requiring implantation
      of a ventricular lead occurs at a rate of 1.7% per year. It is considered that
      AAI/AAIR pacing is safe and reliable as treatment for patients with SSS and
      normal AV conduction.

PMID- 11310308
TI  - Transition from narrow to wide QRS tachycardia: what is the mechanism?

PMID- 11310309
TI  - Lead insertion by supraclavicular approach of the subclavian vein puncture.
AB  - Total occlusion of the left subclavian vein was diagnosed in a 76-year-old
      patient, 6 years after implantation of an ICD with VVI pacing backup. Replacement
      of the ICD included upgrading of the ICD system because of the presence of
      pacemaker syndrome when the patient was VVI paced. Insertion of an atrial lead
      through the ipsilateral vein system was made possible by using the
      supraclavicular approach of the subclavian, enabling puncturing of the left
      subclavian vein medially to the obstruction.

PMID- 11310310
TI  - Oozing from the pericardium as an etiology of cardiac tamponade associated with
      screw-in atrial leads.
AB  - Screw-in atrial pacing leads are widely used. Cardiac tamponade is a
      complication. An 81-year-old woman with advanced atrioventricular block underwent
      permanent pacemaker implantation and subsequently developed cardiac tamponade. At
      surgery, the lead-tip screw was found penetrated through the right atrium but not
      through the pericardium. The source of bleeding was confirmed to scratching the
      inner pericardial membrane by the screw tip. Although cardiac tamponade due to
      perforation and leakage is known, tamponade caused by the trauma of an atrial
      screw on the pericardium with resultant ooze is less well described.

PMID- 11310311
TI  - Atypical atrial flutter involving the isthmus between the right pulmonary veins
      and fossa ovalis.
AB  - Typical atrial flutter, counterclockwise or clockwise movement around the
      tricuspid annulus, has been well studied. However, the reentrant circuits in
      atypical atrial flutter are not well defined. A patient without a prior history
      of cardiac surgery who presented with incessant atypical atrial flutter is
      described. Activation mapping demonstrated a circular movement around the fossa
      ovalis in the interatrial septum. Entrainment mapping demonstrated a protected
      isthmus between the right pulmonary veins and the fossa ovalis. Radiofrequency
      ablation of this isthmus terminated atrial flutter without recurrence during the
      follow-up period.

PMID- 11310312
TI  - Excimer laser-assisted extraction of an infected bipolar left ventricular pacing
      lead implanted 10 years ago.
AB  - Routine intraoperative transesophageal echocardiography (TEE) revealed a
      previously undiscovered ventricular positioning of an infected ventricular lead
      left in place for 10 years. This case report describes successful removal of this
      lead from the left ventricle by means of excimer laser and discusses some
      important aspects to be considered.

PMID- 11310313
TI  - Symptomatic atrial pacemaker lead thrombosis: detection by echocardiography and
      successful surgical treatment.
AB  - Formation of thrombi on a permanent pacemaker lead is a rare complication of
      pacing. However, because of its serious outcome it should be suspected in a
      patient who reveals right-sided heart failure, dyspnea, or syncope. An early
      decision to perform an echocardiographic examination, followed by surgical or
      thrombolytic treatment can solve this clinical problem. In a 69-year-old woman
      with increasing signs of congestive heart failure, echocardiography revealed a
      mobile mass in the right atrium attached to the pacemaker lead. Because of
      threatened symptoms and large dimensions of the mass, urgent surgical removal of
      the endocardial lead was successfully performed.

PMID- 11310314
TI  - Central venous access resulting in selective failure of ICD defibrillation
      capacity.
AB  - In a patient with a defibrillator system incorporating a lead with integrated
      bipolar sensing, physical contact between a guidewire (inserted for venous
      access) and the right ventricular defibrillation coil created sensing artefacts
      that triggered an inappropriate discharge. The presence of the guidewire in the
      heart during the discharge resulted in an electrical short with irreversible
      damage to the generator and rendered it incapable of delivering further high
      voltage therapy.

PMID- 11310315
TI  - The hot can: ICD failure presenting as severe shoulder pain.
AB  - We describe a patient whose presentation of ICD generator failure was
      excruciating shoulder pain lasting 3 hours. This painful episode prompted
      evaluation and subsequent generator replacement. Destructive analysis of the
      explanted device revealed a short circuit of three battery filter capacitors,
      which resulted in the battery "dumping" its full energy very rapidly, since the
      impedance across the battery terminal was < 1 ohm. The duration of the painful
      episode was equal to the estimated ICD battery life under this low impedance
      condition.

PMID- 11310316
TI  - The role(s) of the industry employed allied professional.

PMID- 11310317
TI  - Retention of water-borne bacteria by membrane filters. Part III: Bacterial
      challenge tests on 0.1 micron rated filters.
AB  - Clear performance differences were observed between different 0.1 micron rated
      filters in terms of their microbial removal efficiency when challenged with
      naturally occurring waterborne bacteria from a water source. Penetration occurred
      with three 0.1 micron rated "sterilizing grade" filter types tested, from three
      different filter manufacturers, that did not have a specific high titer reduction
      claim for Acholeplasma laidlawii. Bacteria shown to penetrate these 0.1 micron
      rated filters were quite similar to those recovered downstream of 0.2.0.22 micron
      rated filters (described in Part II). All of the isolates identified via FAME
      analyses were common environmental or ubiquitous organisms, and some, such as
      Acidovorax sp. and Hydrogenophaga pseudoflava, have also been isolated from
      pharmaceutical water systems. In contrast, four different 0.1 micron rated
      "sterilizing grade" filter types from two different manufacturers, which had been
      qualified with both B. diminuta and A. laidlawii, consistently produced sterile
      effluents under similar test conditions. This study thus highlights the need for
      an industry or regulatory standard method of defining the microbial removal
      performance of 0.1 micron rated filters, and supports the use of functionally
      qualified 0.1 micron rated filters as sterilizing grade filters in pharmaceutical
      operations for enhanced sterility assurance.

PMID- 11310319
TI  - Rationalization and valid scale-up of integrity test parameters for sterilizing
      grade membrane filter cartridges.

PMID- 11310318
TI  - Investigation of a filter structure by microbial retention studies: a synthesis
      and elaboration of prior findings.

PMID- 11310320
TI  - Relative appropriateness of the 0.1 or 0.2 micron-rated membrane filters to serve
      as sterilizing devices.

PMID- 11310321
TI  - Real compliance and how to achieve it.
AB  - Regulatory compliance is designed to comply with regulations and guidelines to
      avoid regulatory citations. While it is designed to minimize compliance problems,
      it can actually create them by causing a company to aim at constantly moving
      targets, domestically and internationally. This type of compliance substantially
      increases costs. Real compliance offers the advantages of regulatory compliance
      without the disadvantages at significantly reduced costs by increasing production
      and control efficiencies and reducing training expense. Real compliance is
      defined as a state of control. It is unconditional since it does not depend on
      compliance with a particular set of regulations and guidelines. Real compliance
      is product and process based and results from effective policies, procedures,
      processes, and warning systems. Real compliance can be achieved by designing
      systems and procedures to contain the characteristics outlined in the elements of
      a state of control listed above. The following points should be considered as you
      transform regulatory compliance to real compliance. Knowledge plus control equals
      compliance Build effective processes and monitor them Cease dependence on
      inspection to achieve quality Develop and implement effective quality systems
      Systems and procedures should be principle-based, not rule-based Hire the best
      people, train them and keep them Have enough staff Build an "immune system" Never
      guess.

PMID- 11310322
TI  - Retention of water-borne bacteria by membrane filters. Part I: Bacterial
      challenge tests on 0.2 and 0.22 micron rated filters.
AB  - The results of bacterial challenge tests conducted on several 0.2 and 0.22 micron
      rated "sterilizing grade" filter cartridge types with bacteria from a natural
      water source are presented. Eight different 0.2/0.22 micron rated "sterilizing
      grade" filter types from four different filter manufacturers, claimed to be
      capable of retaining Brevundimonas diminuta at a challenge level of 10(7)
      CFU/cm2, were tested. The filters tested included nylon 6.6 and polyamide filters
      from two manufacturers, modified or hydrophilic PVDF filters from two
      manufacturers, modified or asymmetric PES filters from three manufacturers, and
      cellulose acetate filters from a single manufacturer. Consistent bacterial
      penetration was observed, over the 18-24 h challenge period, for all twenty-five
      integral 0.2 and 0.22 micron rated filter cartridges tested, at challenge levels
      of about 10(1)-10(4) CFU/cm2, indicating that natural waterborne bacteria were
      more penetrative than B. diminuta. The observed penetration was thus
      qualitatively independent of filter media type or manufacturer. These results add
      to the growing body of evidence that shows 0.2 and 0.22 micron rated filters may
      not remove all microorganisms under all conditions. These results further
      establish that bacterial penetration of 0.2/0.22 micron rated filters is not
      limited just to (1) specific membrane types, or (2) extended duration challenges
      (>> 24 h), or (3) extremely high challenge levels, or (4) bacteria that can only
      exist in a penetrative state in an artificial laboratory setting.

PMID- 11310323
TI  - Retention of water-borne bacteria by membrane filters. Part II: Scanning electron
      microscopy (SEM) and fatty acid methyl ester (FAME) characterization of bacterial
      species recovered downstream of 0.2/0.22 micron rated filters.
AB  - The results of scanning electron microscopic (SEM) and fatty acid methyl ester
      (FAME) characterization of the bacterial species shown to penetrate conventional
      0.2/0.22 micron rated "sterilizing grade" filters are presented. SEM data suggest
      that retention of bacteria by these filters appears to be strongly influenced by
      the morphology, and especially the width of bacteria and less so by length. When
      the bacterial cell width is small, less than 0.3 micron or so, the cell length
      does not appear to limit the ability to penetrate 0.2/0.22 micron rated filters.
      As the bacterial width increases, there is also a strong, almost exponential,
      decrease in the allowable length for penetration, with most penetrative cells
      tending to be coccoid beyond a width of 0.5 micron. Significant percentages of
      the bacteria (40-50%) that were observed downstream of these filters were larger
      than B. diminuta, the standard organism used to qualify 0.2/0.22 micron rated
      filters. The average sizes of natural waterborne bacteria that penetrated the
      filters tested were 20-40% larger in width, and 40-70% larger in length, compared
      to B. diminuta. These results indicate that size exclusion is not the sole
      mechanism governing bacterial retention. All isolates identified via FAME
      analyses were common environmental or ubiquitous organisms, and some, such as
      Acidovorax sp. and Hydrogenophaga pseudoflava, have also been isolated from
      pharmaceutical water systems. Most of the bacteria recovered downstream of
      0.2/0.22 micron rated filters were gram negative, oxidase positive, motile,
      nonfermentors.

PMID- 11310324
TI  - [Recognizing the signs of time].

PMID- 11310325
TI  - [Antibacterial and wound healing: double action of hydrogel].

PMID- 11310326
TI  - [I have no more pain].

PMID- 11310327
TI  - [Prenatal diagnosis yields no information about the unborn child].

PMID- 11310328
TI  - [Problems in the nutrition of the infants with cleft lip and palate].

PMID- 11310329
TI  - [Parents and children in school].

PMID- 11310330
TI  - [Neurodermatitis: do not scratch!].

PMID- 11310331
TI  - [Parents' role in pediatric care: when the child must be hospitalized].

PMID- 11310332
TI  - [Pediatric home care: instructions from the family].

PMID- 11310333
TI  - [Epizoonoses: the importance of hygiene].

PMID- 11310334
TI  - [Economics of nursing, a field in itself].

PMID- 11310335
TI  - [Young patients must be protected from self-inflicted injury as well as from
      being injured by others].

PMID- 11310336
TI  - [Legislation of working hours: implications for nurses].

PMID- 11310337
TI  - [Work certificates: it is time for a new approach].

PMID- 11310338
TI  - Taking an Intranet an extra step.

PMID- 11310339
TI  - Continuity of kids' care.

PMID- 11310340
TI  - Gathering I.T. intelligence.

PMID- 11310341
TI  - Recruiting and retaining staff always on CIO's minds.

PMID- 11310342
TI  - A friendly but firm approach to consultants.

PMID- 11310343
TI  - ROI is key to selling other C's.

PMID- 11310344
TI  - Provider organizations are moving at an acceptable pace to implement I.T. that
      can help reduce medical errors. Do you agree or disagree?

PMID- 11310345
TI  - Phasic production of urinary pyridinium crosslinks in mice: the effect of
      ovariectomy.
AB  - Considerable sample to sample variability in deoxypyridinoline
      crosslink/creatinine (Dpd/CREAT) ratio values was confirmed when twice-weekly
      sampling for 77 days was performed in C57 mice. Analysis of samples from
      individual mice indicated that, in the majority of mice in a given group (54
      67%), phasic changes occurred with periodic peaks as much as 4-5 times basal
      values. Alignment of peaks in the individual time courses of mice revealed a
      clear cyclic crosslink production (periodicity 12-14 days) for the population,
      although not all mice gave a peak in every case. Ovariectomy (OVX) (compared to
      sham-operated mice) increased mean values of crosslink production by either C57
      or C57 x 129 F1 mice from about 10 days after operation with highest values
      between 21 and 35 days, and then a decrease in the difference between sham and
      OVX, particularly in C57 mice. Analysis of both time courses for individual mice
      and distribution curves of the data from groups of mice indicated that OVX
      consistently increased basal crosslink values (6-9 ratio units) with phasic peak
      values superimposed. The peak alignment analysis reinforced this observation. The
      influence of the background variability was avoided by pooling data over one
      cycle time and the use of nonparametric statistics, and the effect of OVX was
      analyzed in several strains of mice. Crosslink levels and phasic production
      declined with age but were also influenced by manipulation of the mice,
      suggesting that experimental conditions should be rigorously controlled when this
      urinary crosslink measure is used as a parameter in mouse models of OVX-induced
      osteoporosis.

PMID- 11310346
TI  - Quantification of the expression levels of lysosomal cysteine proteinases in
      purified human osteoclastic cells by competitive RT-PCR.
AB  - Cathepsin K is a lysosomal cysteine proteinase (LCP) predominantly expressed in
      osteoclasts. This study was conducted to evaluate the importance of human
      cathepsin K for osteoclastic bone resorption relative to that of other LCPs. To
      accomplish this, we quantitatively determined the expression levels of major LCPs
      (cathepsins B, K, L, and S) in human osteoclastic cells by using competitive RT
      PCR. Giant cell tumor of bone (GCT) was used as a source of human osteoclastic
      cells, since the tissue was shown to contain a large number of cells satisfying
      the criteria for typical osteoclasts. The involvement of LCPs in the bone
      resorption process by the GCT cells was confirmed by showing that trans
      epoxysucciny-L-leucylamido-(4-guanidino) butane (E-64), a nonselective cysteine
      proteinase inhibitor, exerted an inhibitory effect on the pit formation. We
      isolated osteoclast-like cells (OLCs) positive for tartrate-resistant acid
      phosphatase (TRAP) and cathepsin K from the GCT tissue to a degree of almost 95%
      purity. In these cells, the expression of cathepsin K was shown to be
      approximately 20-, 130-, and 410-fold stronger than that of cathepsins B, L, and
      S, respectively. A similar result was obtained when human bone marrow cells in
      culture were used as another source of OLCs. Further, we found that cathepsin K
      was expressed in OLCs far more strongly than in several human nonosteoclastic
      cells including osteoblastic cell lines. The abundant and selective expression of
      cathepsin K in OLCs relative to that of other LCPs suggests that cathepsin K is
      mainly responsible for osteoclastic degradation of human bone matrix.

PMID- 11310347
TI  - The endothelin receptor antagonist, L-754,142 does not prevent cyclosporine A
      induced osteopenia in rats.
AB  - Cyclosporine A (CsA) is a potent immunosuppressive agent widely used to prevent
      allograft rejection. In vivo administration of CsA is associated with the
      development of high-turnover osteopenia. Endothelin-1 (ET), a vasoconstrictive
      peptide, has been implicated in CsA-induced nephrotoxicity and hypertension.
      Recent evidence suggests that endothelin plays a pivotal role in bone metabolism.
      The present study was designed to investigate whether L-754,142 (ETRA), the
      combined endothelin A and B receptor antagonist, when given to rats, would
      favorably modify the bone loss caused by CsA. Fifty, 5-month-old male Sprague
      Dawley rats were randomly divided into five groups of 10 rats each. The first
      group served as a basal control. The remaining four groups received, by daily
      gavage for 28 days, (1) a combined CsA and ETRA vehicle, (2) CsA, 10 mg/kg, (3)
      ETRA, 30 mg/kg, and (4) CsA, 10 mg/kg and ETRA, 30 mg/kg, respectively. Rats were
      weighed and venous blood was collected on days 0, 14, 28 for determination of
      BUN, creatinine, calcium, PTH, osteocalcin, and 1,25(OH)2 D. Tibiae, after double
      labeling, were removed following sacrifice for histomorphometry. Both CsA-treated
      rats and CsA/ETRA-treated rats demonstrated trabecular osteopenia with raised
      serum osteocalcin, and 1,25(OH)2D levels when compared to control animals (P <
      0.05). Rats given CsA alone developed renal impairment, as shown by an increased
      BUN. The combination group did not develop renal impairment. The results suggest
      that endothelin may contribute to the development of CsA-induced nephrotoxicity,
      which was prevented by ETRA, but does not seem to play a role in CsA-induced
      osteopenia.

PMID- 11310348
TI  - Baseline expression and effect of TGF-beta 1 on type I and III collagen mRNA and
      protein synthesis in human odontoblasts and pulp cells in vitro.
AB  - Since growth factors have been suggested to regulate dentin collagen formation in
      response to external irritation, we investigated the effect of TGF-beta 1 on pro
      alpha 1 (I) collagen mRNA expression in cultured mature human odontoblasts and
      pulpal fibroblasts, as well as cultured human pulp tissue, using quantitative
      PCR. Cultured gingival fibroblasts (GF) and osteoblasts (OB) served as controls.
      Also, type I collagen synthesis in cultured odontoblasts and pulp tissue, as well
      as type III collagen synthesis in odontoblasts, were studied by measuring
      respective procollagen (PINP and PIIINP) secretion into culture media with radio
      immunoassay (RIA). Odontoblasts expressed significantly higher basic level of
      type I collagen mRNA than pulp tissue or pulp fibroblasts in culture, but
      markedly lower level than GF and OB cells. TGF-beta 1 (10 ng/ml) had negligible
      effects on type I collagen mRNA expression or PINP synthesis in cultured
      odontoblasts and pulp tissue, and PIIINP synthesis in the odontoblasts. In PF
      cells, the effect of TGF-beta 1 depended on culturing conditions; a 6-fold
      increase in mRNA expression was observed using serum-free medium but no effect
      was seen in the cells cultured with 10% FBS. In contrast, GF cells serving as
      controls were not markedly affected by the culture conditions, with 2-3-fold
      increase in mRNA expression by TGF-beta 1. These experiments demonstrate that
      mature human odontoblasts are capable of synthesizing type III collagen protein,
      and that TGF-beta 1 has negligible effect on mature human odontoblast and pulp
      tissue collagen expression.

PMID- 11310349
TI  - Growth hormone secretion and sensitivity in men with idiopathic osteoporosis.
AB  - Previous studies have suggested that insulin-like growth factor-I (IGF-I) and its
      binding proteins (IGFBPs) have a pathogenetic role in idiopathic osteoporosis. To
      investigate this question further we compared 20 men with idiopathic osteoporosis
      with 12 healthy, age-matched men regarding growth hormone (GH) secretion and
      sensitivity. GH samples were drawn every 30 minutes for 24 hours from 12 of the
      patients and all controls, and cumulated GH secretion (24 hGH) was derived. Peak
      GH secretion (peakGH) was provoked by an insulin tolerance test. There were no
      differences between the groups in serum IGF-I (162 +/- 30 vs 163 +/- 47
      micrograms/liter, mean +/- SD), IGFBP-3 (2474 +/- 263 vs 2568 +/- 197
      micrograms/liter), 24 hGH (1.34 +/- 1.26 vs 0.79 +/- 0.43 U), or peakGH (53.0 +/-
      21.5 vs 44.1 +/- 19.8 mU/liter). Patients and controls were given GH (2.4 U/day)
      for 1 week. Serum levels of markers for bone turnover increased significantly in
      both groups, with no difference in response to GH between the groups. The
      increase in urinary bone resorption markers was only significant in the controls.
      In the patients, but not in the controls, there were significant positive
      correlations between indices for GH secretion and markers for bone turnover at
      baseline and significant negative correlations with relative changes in bone
      markers during GH treatment. In this study no difference in GH secretion was
      found between men with idiopathic osteoporosis and controls, but the findings
      suggest that the GH/IGF-I axis could play a regulatory role in bone metabolism in
      men with this condition.

PMID- 11310350
TI  - A comparison of spinal quantitative computed tomography with dual energy X-ray
      absorptiometry in European women with vertebral and nonvertebral fractures.
AB  - Quantitative computed tomography (QCT) was compared to dual X-ray absorptiometry
      (DXA) measured in the lumbar spine of 508 European women defined as normal
      without fracture (NoF), or osteoporotic (OP), with either vertebral fracture
      (VF), or peripheral fracture (PF). The correlations between QCT and DXA BMD
      measurements were significantly different in normal and in osteoporotic patients,
      indicating that the two exams do not measure the same bone aspects. According to
      ROC curves results, QCT Z-scores separate OP from NoF with better sensitivity
      than all other measurements. A threshold to differentiate OP from NoF was chosen
      at Z-score = -1 for DXA-BMD and -1.5 for QCT-BMD. VF patients showed a highly
      significant decrease in BMD by DXA or QCT. PF patients revealed measurements
      lower than those of normal subjects but greater than those of VF, calling into
      question the idea of a diffuse osteoporosis causing nonvertebral fractures that
      is measurable by spinal DXA or QCT. DXA is weakly dependent upon age, and T-score
      or Z-score are equivalent for evaluating osteoporosis. QCT depends greatly upon
      age, and Z-score appears to be more efficient.

PMID- 11310351
TI  - Bone mass and mineral metabolism in liver transplant patients treated with FK506
      or cyclosporine A.
AB  - The purpose of this study was to compare the effects of Cyclosporine A (CyA) and
      FK506 on bone mass and mineral metabolism in liver transplantation (LT) patients.
      A prospective study was performed on 18 male patients who underwent LT treated
      with CyA, and 7 LT patients who received FK506. Bone mineral density (BMD) of the
      lumbar spine and proximal femur (DPX-L) was measured before and at 6, 12, and 24
      months after transplantation. Moreover, intact parathyroid hormone (PTH) and 25
      hydroxyvitamin D (25OHD) levels were determined at the same time. The cumulative
      dose of glucocorticoids was calculated in all patients. At 6 months, lumbar BMD
      decreased 5.2 +/- 1.2% (P = 0.0005) and 2.9 +/- 2.1% (p = ns) in CyA and FK506
      groups, respectively. Lumbar BMD reached baseline values at 1 year in the FK506
      group and 2 years after LT in the CyA group. Moreover, significant intergroup
      differences in femoral neck BMD changes after 2 years of transplant were observed
      (CyA: -5.2 +/- 1.97 versus FK506: +1.55 +/- 2.2%; P = 0.039). In the first year
      posttransplant both groups showed a marked increase in PTH and 25OHD levels. The
      mean cumulative dose of glucocorticoids was higher in the CyA group (CyA group
      11.06 +/- 0.46 g versus FK 506 group 6.71 +/- 0.42 g; P < 0.001), and multiple
      linear regression analysis showed a negative correlation between BMD changes at
      the lumbar spine and mean cumulative dose of glucocorticoids (P = 0.022). In
      conclusion, our data suggest that after liver transplantation treatment with
      FK506 shows a more favorable long-term effect on bone mass evolution than CyA
      therapy. These differences seem to be associated with the lower dose of
      glucocorticoids used in the FK506 group.

PMID- 11310352
TI  - In vitro and in vivo induction of bone formation using a recombinant adenoviral
      vector carrying the human BMP-2 gene.
AB  - It has been well established that bone morphogenetic protein-2 (BMP-2) can induce
      bone formation both in vivo and in vitro, although high concentrations (up to
      milligrams) of BMP-2 have been required to achieve this effect in vivo. Further,
      clinical applications are usually limited to a single dose at the time of
      implantation. In an attempt to prolong the transforming effect of BMP-2 we used a
      recombinant adenoviral vector carrying the human BMP-2 gene (Adv-BMP2) to
      transduce marrow-derived mesenchymal stem cells (MSC) of skeletally mature male
      New Zealand white rabbits. The pluripotential MSC were incubated with Adv-BMP2
      overnight followed by culture in growth medium for 1 week. Assays on tissue
      cultures demonstrated that these Adv-BMP2 transduced MSC produced BMP-2 protein,
      differentiated into an osteoprogenitor line, and induced bone formation in vitro.
      These MSC had increased alkaline phosphatase activity, increased expression of
      type I collagen, osteopontin, and osteocalcin mRNA, and induced matrix
      mineralization compared with both non-transduced cells and cells transduced with
      a control adenoviral construct. To analyze the osteogenic potential in vivo, Adv
      BMP2-transduced MSC were autologously implanted into the intertransverse process
      space between L5 and L6 of the donor rabbits. The production of new bone was
      demonstrated by radiographic examination 4 weeks later in areas implanted with
      cells transduced with Adv-BMP2, whereas no bone was evident at sites implanted
      with cells transduced with the control adenoviral construct. Histological
      examination further confirmed the presence of new bone formation. These
      accumulated data indicate that it is possible to successfully transduce
      mesenchymal stem cells with a recombinant adenoviral vector carrying the gene for
      BMP-2 such that these cells will produce BMP-2, differentiate into an
      osteoprogenitor line, and induce bone formation both in vitro and in vivo.
      Moreover, incubation of the Adv-BMP2-transduced cells for an additional 7 days in
      culture before transplantation enhances the success rate in bone formation (three
      out of three) as compared with our previous report (one out of five, Calcif
      Tissue Int 63:357-360, 1998).

PMID- 11310353
TI  - The effect of monocyclic and bicyclic analogs of human parathyroid hormone (hPTH)
      (1-31)NH2 on bone formation and mechanical strength in ovariectomized rats.
AB  - The [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 lactam is a stronger stimulator of
      adenylyl cyclase activity and a better stimulator of trabecular bone in the
      ovariectomized (OVX) rat model of osteopenia than hPTH-(1-31)NH2. This enhanced
      activity is due in large part to the stabilization of the amphiphilic receptor
      binding alpha-helix in the Ser17-Gln29 region. The goal of the present study was
      to determine whether further cyclization could produce a more active hPTH analog.
      To this end, we compared the relative bioactivities of the bicyclic hPTH analog
      [Glu17,Leu27]cyclo(Lys13-Glu17,Glu22-Lys26)-hPTH-(1-31)NH2, made by replacing
      Ser17 with Glu17 and introducing a second lactam linkage between Lys13 and Glu17.
      The relative EC50 for adenylyl cyclase stimulation by the bicyclic hPTH analog
      was similar to the EC50 of the monocyclic [Leu27]cyclo(Glu22-Lys26)-hPTH-(1
      31)NH2, but the bicyclic analog was still more active than hPTH-(1-31)NH2. As
      expected from adenylyl cyclase stimulation being responsible for PTH's anabolic
      action, the bicyclic hPTH analog [Glu17, Leu27]cyclo(Lys13-Glu17, Glu22-Lys26)
      hPTH-(1-31)NH2 was able to increase femoral trabecular volume and thickness and
      mechanical strength in OVX rats, but it was no more effective than
      [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 when injected once daily in a dose of
      0.8 nmol/100 g body weight. Thus, further constraint of the conformation of hPTH
      (1-31)NH2 by introducing two lactam link-ages between Lys13-Glu17 and Glu22-Lys26
      did not raise the osteogenicity above that of the monocyclic analog.

PMID- 11310354
TI  - Improving the physical health of patients with schizophrenia: therapeutic
      nihilism or realism?
AB  - Schizophrenia is associated with a raised mortality due to both an increase in
      suicide and factors related to poor physical health. The increased rates of
      gastrointestinal, respiratory and cardiovascular disease in this population are
      likely to be due to high rates of smoking and obesity accompanied by a poor diet,
      lack of exercise and the side effects of medication. The evidence suggests that
      such risk factors in the schizophrenic population are largely ignored by the
      medical profession. Research to date has failed to address the health needs of
      this vulnerable population. Systematic research, with the aim of assessing the
      potential benefits of health improvement measures, should be a matter of
      priority.

PMID- 11310355
TI  - Post exertional broad complex tachycardia in a normotensive patient: a rare
      presentation of phaeochromocytoma.
AB  - Phaeochromocytomas are rare cause of secondary hypertension with significant
      morbidity and mortality, if left untreated. Paroxysms with hypertension are
      considered as "textbook" presentations but atypical forms represent considerable
      diagnostic challenge. We report an unusual association between phaeochromocyotoma
      and post-exertional malignant arrhythmia in a normotensive subject.

PMID- 11310356
TI  - An unusual cause of calf pain.
AB  - Popliteal artery entrapment syndrome is an unusual presentation of calf pain to
      an accident and emergency department. We report the case of a 36-year-old man
      presenting with left calf pain and investigations confirmed the diagnosis of
      popliteal artery entrapment syndrome. A&E doctors should consider this diagnosis
      in their differential diagnoses for calf pain in younger patients particularly
      when obvious trauma is absent.

PMID- 11310357
TI  - Sarcoma arising adjacent to a total hip arthroplasty.
AB  - We present the case of a 79-year-old woman who developed a high grade spindle
      cell sarcoma adjacent to total hip arthroplasty 13 years after the index
      operation. MRI scan appeared to show a direct communication between the tumour
      and intra medullary canal through a breach in the femoral cortex.

PMID- 11310358
TI  - "And afterwards your body to be given for public dissection": a history of the
      murderers dissected in Glasgow and the west of Scotland.
AB  - Between 1752 and 1832, the bodies of hanged murderers were dissected or gibbeted.
      During this period, 38 murderers were executed in the West of Scotland. The
      bodies of at least 23 were dissected in Glasgow. The stories of these murders are
      recounted. Insight is also given into the attitudes of the public and the
      anatomists to dissection of executed murderers.

PMID- 11310359
TI  - Waiting times--what are they and can these be prioritised? A personal opinion.

PMID- 11310360
TI  - Survey of provision of echocardiography in Scottish district general hospitals.
AB  - A telephone survey of echocardiography services in district general hospitals in
      Scotland was carried out in 1999. The study showed wide variation in the
      echocardiography services among the district hospitals in terms of equipment,
      personnel and service provision. The number of echocardiograms performed by a
      centre is partly dependent on the demand but is more critically influenced by the
      local provision of service. In particular, sufficient numbers of trained
      technicians hold the key to efficient high output services. The survey has
      provided a platform for comparison of echocardiography services among the
      district general hospitals in Scotland. We hope that this will encourage
      individual district hospitals to audit their echocardiography service with a
      special emphasis on the role of the technician.

PMID- 11310361
TI  - The role of spiral computed tomography and D-dimer in pulmonary embolism.
AB  - The first part of this study retrospectively compared the discriminatory power of
      spiral CT versus clinical findings in 112 consecutive patients referred with
      chest pain or dyspnoea. Spiral CT exhibited a sensitivity 91.9%; specificity
      98.7%; PPV 97.1%; NPV 96.1%; accuracy 96.4%. No other test or clinical parameter
      had acceptable accuracy. The SimpliRED test is a latex method of estimating the
      level of D-dimer. The second part of this study determined that, in a similar
      consecutive series of patients referred for lung scintigrams, although SimpliRED
      tests had a NPV 95.5%, 59/126 (46.8%) consecutive were positive. However on the
      basis of clinical effectiveness and cost, imaging for suspected pulmonary
      embolism should be based on a combination of D-dimer estimation and spiral CT.

PMID- 11310362
TI  - The risks of ear piercing in children.
AB  - Body piercing, and particularly ear piercing is becoming increasingly common in
      young children who may not be capable of properly caring for the pierced site.
      This may result in infection at the site and embedding of the earring. Infection
      and the subsequent necessity of removal of such earrings can cause considerable
      pain and distress. There is also a proven risk of inducing nickel allergy in
      these children which can be a problem in later life. The potential for serious
      infection such as Hepatitis B, Hepatitis C and HIV is not appreciated by the
      parents of these children.

PMID- 11310363
TI  - Belly-button brothers. Stem cells from umbilical cords saved their lives.

PMID- 11310364
TI  - Snack attack! Kids are eating a lot more calories between meals--and they have
      the bellies to prove it.

PMID- 11310365
TI  - Puppy love's bite. Romance is great for adults. But a new study finds it can lead
      to depression for the young.

PMID- 11310366
TI  - Three-dimensional ultrasound with surface rendering for the study of fetal small
      parts.
AB  - The purpose of this article is to report that the use of three-dimensional (3D)
      ultrasound with surface rendering offers advantage in fetal small parts
      evaluation. Compared with two-dimensional (2D) ultrasonography, three-dimensional
      ultrasonography provides a better spatial vision of the surface and anatomic
      boundary of different embryonal and fetal organs and structures. Visualization of
      an embryo or fetus in all space planes with surface rendering allows a more
      detailed evaluation of external fetal structures that could easily be missed with
      2D ultrasonography. The advent of 3D ultrasound has dramatically improved
      clinical prenatal diagnosis of small parts anomalies. We anticipate that 3D
      ultrasonography will be used more widely in obstetrics.

PMID- 11310367
TI  - Diagnostic screening for mucopolysaccharidoses by the dimethylmethylene blue
      method and two dimensional electrophoresis.
AB  - BACKGROUND: The diagnosis of a mucopolysaccharidosis (MPS) can be achieved by non
      enzymatic screening methods, including two-dimensional electrophoresis (2-D EP),
      and the dimethylmethylene blue (DMB) method. However, the confirmation of MPS
      diagnosis is difficult to achieve in Taiwan due to the shortage of a well
      established MPS diagnostic service. In this article, we introduce the MPS
      screening protocols we have already established, and also illustrate the
      interpretation of 2-D EP result for MPS typing determination. METHODS: Thirty
      seven patients with different types of MPS were analyzed by 2-D EP and the DMB
      method. They were 4 with MPS I (Hurler), 15 with MPS II (Hunter), 10 with MPS III
      (Sanfilippo), 5 with MPS IV (Morquio), and 3 with MPS VI (Maroteaux-Lamy).
      RESULTS: The electrophoretic patterns of the affected glycosaminoglycans (GAGs)
      in different MPS were illustrated, which were the basis of MPS diagnosis. The DMB
      results showed a significant difference between these diseases, and the
      dimethylmethylene blue/creatinine (DMB/CRE) ratio of Hunter Syndrome was markedly
      greater than those of the Sanfilippo, Hurler, and Maroteaux-Lamy Syndrome,
      successively. The 2-D EP is also applicable for MPS prenatal diagnosis. One cell
      free amniotic fluid with suspected Hunter Syndrome was analyzed by 2-D EP, and
      the results excluded the possibility of MPS which was confirmed by enzymatic
      study. CONCLUSIONS: The 2-D EP provides a good separation of urinary GAG, and the
      DMB method gives an estimation of the GAG concentration in the urine. Both of the
      methods are specific, sensitive, and easy to perform for MPS screening and
      diagnosis.

PMID- 11310368
TI  - Microsurgical treatment of deep arteriovenous malformations--basal ganglia and
      thalamus.
AB  - BACKGROUND: Surgery for deep nuclei arteriovenous malformations (AVMs) is
      controversial after the introduction of stereotactic irradiation and
      embolization. However, rupture of an AVM in this location can lead to
      catastrophic parenchymal or intraventricular hemorrhage. Thus, microsurgery still
      has its place in treatment of such lesions to prevent the untreated AVM bleeding
      or rebleeding. We present a series of 16 AVMs located in the deep nuclei treated
      by direct microsurgery before radiosurgery was available in 1993. METHODS: We
      reviewed the clinical and angiographic characteristic of 16 patients with deep
      seated AVMs (three in caudate nucleus, three in lentiform nucleus and ten in
      thalamus). The surgical approach was described separately depending upon the
      location of the AVMs. The surgical outcomes were classified as excellent
      (symptoms improved), good (no additional neurological deficit), fair (minor
      neurological deficit), bad (major neurological deficit) and dead. RESULTS:
      Complete AVM elimination was achieved in 16 patients (100%) in one-stage
      operation. Eleven patients had excellent or good outcomes, three had fair
      outcomes and two had bad outcomes. There were no deaths in this series. Two
      patients had permanent hemiparesis to make a late morbidity rate of 12.5%.
      CONCLUSIONS: With improving microsurgical techniques, neuroimaging and
      neuroanesthesia, difficult and deeply hidden AVMs can be successfully resected
      under microsurgery with an acceptably low morbidity and mortality rate.

PMID- 11310369
TI  - Should asymptomatic atrophic retinal holes be treated prophylactically in
      pseudophakic eyes after Nd:YAG laser posterior capsulotomy?
AB  - BACKGROUND: Retinal detachment (RD) following cataract extraction is a serious
      and potentially sight-threatening event that will often necessitate further
      surgical intervention. Of the several risk factors reported in the literature,
      Neodymium:YAG laser posterior capsulotomy has been reported to increase the risk
      of RD following cataract surgery up to 4.9-fold. The purpose of this study is to
      investigate the difference of characteristics in pseudophakic RD with or without
      Nd:YAG laser posterior capsulotomy and the possible role of atrophic retinal
      holes in pseudophakic RD after posterior capsulotomy. METHODS: Retrospective
      review of 78 cases of pseudophakic RD after uncomplicated extracapsular lens
      extraction and intraocular lens implantation was done. Twenty-one of them
      received Nd:YAG laser posterior capsulotomy before RD. We measured the numbers,
      types, and locations of retinal breaks and several other risk factors associated
      with RD. Analysis was performed with the system of Statistical Products and
      Services Solutions (SPSS). RESULTS: The ratio of retinal holes only in retinal
      breaks that caused retinal detachment was significantly higher in the capsulotomy
      group than the non-capsulotomy group (12/21 vs 14/57, p = 0.05). Only three
      patients in the capsulotomy group claimed significant symptoms before the
      detachment. There was no significant difference in mean number of retinal breaks
      and break location. Other risk factors predisposing to RD did not differ
      significantly between the two groups (13/21 vs 23/57, p = 0.12), nor did the
      interval from cataract surgery to RD (31.20 vs 29.44 months, p = 0.48).
      CONCLUSIONS: This primitive study suggests that asymptomatic atrophic retinal
      holes, usually not regarded as an absolute risk factor for RD, might lead to RD
      preferentially after Nd:YAG laser posterior capsulotomy. Early identification and
      treatment of such breaks might decrease the incidence of pseudophakic RD. We
      suggest that it is necessary to perform detailed preoperative and postoperative
      fundus examination and treat prophylactically any identified breaks, including
      asymptomatic atrophic retinal holes, in pseudophakic eyes after Nd:YAG laser
      posterior capsulotomy.

PMID- 11310370
TI  - Nasopharyngeal angiofibroma.
AB  - BACKGROUND: Nasopharyngeal angiofibromas are uncommon neoplasms, which are
      histologically benign but locally invasive and destructive. They mostly affect
      the nose and nasopharynx, but may extend to the adjacent structures. The first
      choice of treatment is surgery. This paper presents our experience in the
      management of nasopharyngeal angiofibroma. METHODS: We retrospectively reviewed
      13 patients of nasopharyngeal angiofibroma attending the Department of
      Otorhinolaryngology at Taipei Veterans General Hospital (VGH-TPE) from 1979 to
      1999. Two patients recurred after surgery at other hospitals and were excluded
      from this study. Eleven patients underwent the primary surgery and were included
      for statistical analysis. The relationship between preoperative embolization and
      intraoperative effective blood loss (EBL) was also discussed. RESULTS: The
      incidence was about 1 per 5,000 otorhinolaryngology admissions. The ratio of
      female to male was 1 to 10. The median age of symptom onset was 18 years. There
      were 7, 3 and 1 patients in IA, IB and IIA stages of Sessions' classification.
      Seven patients underwent preoperative embolization. One patient was treated with
      stilbestrol preoperatively. Of the surgical procedures, transpalatal approach was
      the most often performed (8/11). Postoperative radiotherapy (1,000 cGy) was
      administered to 1 patient due to the suspected residual tumor. The average
      intraoperative EBL was 731.8 ml. Patients with preoperative embolization had an
      average EBL of 814.3 ml and those without embolization had an average EBL of
      587.5 ml. The difference of EBL between the patients with and without
      preoperative embolization was not statistically significant. The average follow
      up duration was 118.4 months and no tumor recurred. CONCLUSIONS: Surgery is the
      main therapeutic option for nasopharyngeal angiofibroma. We suggest preoperative
      embolization. Radiotherapy is an adjuvant treatment and reserved for the patients
      with advanced stage or recurrent tumors.

PMID- 11310371
TI  - The outcome of shunted hydrocephalic children.
AB  - BACKGROUND: Neurological sequelae and mental retardation may result from
      different etiological types of hydrocephalus. The aim of our study is to
      determine the intellectual development and the "shunt history" of these children
      with regard to the complications and revision rates. METHODS: We reviewed the
      medical history of non-tumoral pediatric hydrocephalic patients who had received
      first shunt insertions between 1983 and 1997 and had been regularly followed up
      at the out-patient clinics of Taipei Veterans General Hospital. These patients
      were categorized into five different etiological groups. Their intelligence test
      scores and the surgical morbidity encountered over this period were used as the
      main outcome measures. RESULTS: Out of the seventy-three patients, post
      meningitis hydrocephalus patients had the significantly highest shunt revision
      rate (2.50 +/- 0.82, p = 0.01). They also showed retardation in IQ scores, but
      the different was not significant when compared with other groups. The results of
      IQ tests were not related to either the age of initial shunt insertion (p =
      0.461) or revision rates (p = 0.292). For physical disabilities, post-meningitis
      hydrocephalic patients showed-highest incidence of epilepsy (40%) while
      hydrocephalic patients associated with myelomeningocele had the highest incidence
      of motor deficits (56.25%). CONCLUSIONS: Childhood hydrocephalic patients had
      different developmental neuroimpairments with respect to different etiologies.
      This study provides information about the physical and mental outcome of post
      operative hydrocephalic patients which is valuable to assist in counsel of their
      families.

PMID- 11310372
TI  - 2-chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia.
AB  - Hairy cell leukemia is an uncommon chronic B cell lymphoproliferative disorder in
      Taiwan and only sporadic cases have been noted. This disease is often found in
      middle-aged men with the typical manifestations of pancytopenia and splenomegaly.
      While tartrate-resistant acid phosphatase (TRAP) stain of the neoplastic cells in
      peripheral blood smear is positive in 90% cases, bone marrow examination is still
      necessary for diagnosis. For treatment, splenectomy and interferon have been the
      standard strategies. Recently, newly-developed purine analogues, 2
      chlorodeoxyadenosine (cladribine) and 2'-deoxycorfomycin (pentostatin), were
      found to achieve long lasting complete remission. Here we reported a 48-year-old
      men who was found to have splenomegaly and bicytopenia incidentally at routine
      physical checkup. Although the TRAP staining of peripheral blood showed negative
      result, hairy cell leukemia was finally diagnosed by bone marrow biopsy. The
      following splenectomy showed a typical picture of hairy cell leukemia on
      pathology, but cytopenia recovered only partially after surgery. One course of
      chemotherapy with cladribine (0.1 mg/kg/day continuous intravenous infusion for 7
      days) was given after recovery from major surgery. The white cell and platelet
      counts normalized after treatment and he carried a stable condition thereafter.
      Since the disease is rare and purine analogues are newly developed, there has
      been no report on using 2-clorodeoxy-adenosine against hairy cell leukemia in our
      country. Here we suggest that newly developed purine analogues such as cladribine
      are the first choice of treatment in cases of hairy cell leukemia.

PMID- 11310373
TI  - Ticlopidine-induced hepatitis.
AB  - Ticlopidine is a commonly prescribed drug in cerebrovascular or cardiovascular
      diseases. Since the first introduction in 1970's, ticlopidine was shown to be a
      relatively safe drug. The adverse effects of ticlopidine were mainly bone marrow
      toxicity and elevation of liver function tests. Ticlopidine-induced hepatitis is
      rare and only 33 cases were reported in previous English literature. The 33 cases
      were mostly categorized in cholestatic liver injury; only 2 cases were
      hepatocellular. In Taiwan, a case of ticlopidine-induced cholestatic hepatitis
      was ever reported. Herein, we present another rare case of ticlopidine-induced
      hepatitis in Taiwan with the nature of hepatocellular injury.

PMID- 11310374
TI  - Renal cell carcinoma metastasized to the ureteral stump.
AB  - A rare case of ureteral stump metastasis 3 months after nephrectomy for a renal
      cell carcinoma is presented. A 62-year-old female had undergone right radical
      nephrectomy 3 months earlier because of renal cell carcinoma in our hospital, and
      she came back due to gross hematuria. Cystoscopy revealed a papillary mass with a
      vascular pedicle protruding from the right ureteral orifice. Transurethral
      resection of the bladder tumor over right ureteral orifice was performed and the
      pathologic result showed clear cell adenocarcinoma, which argued in favor of a
      metastatic lesion from the previous renal cell carcinoma. Ureterectomy and a
      bladder cuff excision were then adopted for this patient, but no residual tumor
      was found over the remaining ureter. Nevertheless, the patient died of cancer 36
      months after the event of ureteral stump metastasis.

PMID- 11310375
TI  - p53 mutation and bcl-2 expression in transitional cell carcinoma of the urinary
      bladder.
AB  - BACKGROUND: The purpose of our study was to examine the frequency of p53 mutation
      and bcl-2 expression in transitional cell carcinoma of the urinary bladder and
      their clinicopathologic correlates. METHODS: A total of 137 patients who
      underwent transurethral resection for primary transitional cell bladder
      carcinomas were enrolled. The paraffin-embedded tissue blocks were recut and
      stained by monoclonal anti-p53 (DO7) and anti-bcl-2 (124) antibodies. The bcl-2
      and p53 immunoreactivity was correlated to tumor grade and pathological stage.
      RESULTS: p53 mutation was identified in 102 patients (78.5%). The mutation was
      most common in grade 3 tumors (95%) as compared to grade 2 (74%) and grade 1
      (80%) tumors, but the difference was not statistically significant (p = 0.289).
      Stage pT2 tumors had higher incidence of p53 mutation (97%) as compared to pTa-1
      tumors (71%, p = 0.0003). Only 17 tumors (13%) expressed bcl-2; the grade 3
      tumors had significantly higher incidence of bcl-2 expression (p = 0.04). The bcl
      2 expression was not related to pathological stage (p = 0.083). There was no
      interrelation between p53 mutation and bcl-2 expression (p = 0.97). Grade 3
      tumors correlated well with invasive disease (p < 0.00001). When grade 2 tumors
      were evaluated separately, p53 mutation was positively correlated with disease
      invasion (p = 0.001). CONCLUSIONS: Grade 3 tumor was the most important variable
      associated with tumor invasion in transitional cell carcinoma of the urinary
      bladder. p53 mutation was positively correlated with invasive disease. Grade 2
      tumors with p53 mutation had greater probability of disease invasion. Expression
      of bcl-2 positively correlated with tumor grade but not pathological stage.

PMID- 11310376
TI  - Hypertension in elderly.

PMID- 11310377
TI  - Profile of hypertension in elderly subjects.
AB  - OBJECTIVE: To study clinical profile of hypertension in elderly subjects.
      METHODS: Two hundred and five consecutive subjects aged 60 years and above
      reporting to preventive cardiology clinic with cardiovascular disorders were
      studied. One hundred fifty six subjects (76.09%) were found to have essential
      hypertension (HTN). Newly detected hypertensives were classified as per JNC-VI
      classification. Detailed clinical examination and laboratory investigations were
      carried out to find evidence of associated ailments with HTN. RESULTS: Most of
      the patients belonged to 60-70 years age group. Mean age was 67.36 +/- 6.23 years
      (range 60 to 90 years) and male to female ratio was 1.44:1. Out of hypertensives
      99 (63.46%) had HTN for long period, while 28 (17.94%), 17 (10.89%) and 12
      (7.67%) belonged to mild, moderate and severe HTN categories, respectively. Out
      of newly detected hypertensives 14 (24.56%) were having isolated systolic HTN.
      Associated clinical conditions in hypertensives were coronary artery disease
      (CAD), non-insulin dependent diabetes mellitus (NIDDM), cerebrovascular disease
      (CVD), left ventricular hypertrophy (LVH) and chronic obstructive pulmonary
      disease (COPD) in 69 (57.05%), 49 (31.41%), 37 (23.71%), 20 (12.80%) and 10
      (6.4%) subjects, respectively. HTN alone was found in 31 (19.87%) subjects only.
      Since most of these patients had other concomitant illnesses such as CAD. NIDDM
      etc. therapy was initiated accordingly. Four (20%) patients with LVH died within
      short period of 1 to 12 weeks. CONCLUSION: HTN is the commonest cardiovascular
      disorder in elderly subjects. CAD, NIDDM and CVD are commonly associated clinical
      conditions. Patients with associated LVH have very high short term mortality.

PMID- 11310378
TI  - L-carnitine moderately improves the exercise tolerance in chronic stable angina.
AB  - OBJECTIVES: To study the safety and efficacy (with reference to exercise ECG
      testing) of oral L-carnitine in chronic stable angina. METHODS: Forty-seven
      patients, 30 men and 17 women, aged 56 +/- 8 years, were randomized to receive L
      carnitine (n = 28) or placebo (n = 19) in the dose of 2 g/day for 3 months. The
      adjuvant treatment was not changed during the study. Patients were evaluated by
      computerized stress test (CST) done at the beginning and end of the trial. The
      parameters assessed were exercise duration, time to onset of ST changes, total ST
      score at peak exercise, rate-pressure product at peak exercise, and time needed
      for the ST changes to recover to baseline. RESULTS: The two groups were
      comparable at the beginning of the study. There was no change in the CST
      parameters in the placebo group at the end of 3 months. In the L-carnitine group
      there was a statistically significant improvement in the exercise duration from
      7.8 +/- 2.2 min to 8.6 +/- 1.8 min (p = 0.006) and in the time needed for the ST
      changes to revert to baseline from 7.2 +/- 3.9 min to 5.7 +/- 3.8 min (p =
      0.019). No change was noted in the time to onset for ST depression, ST score and
      double product. There were no systemic adverse effects or coronary events in
      either group. CONCLUSION: Oral L-carnitine is safe and moderately improves the
      duration of exercise and time to recovery of ST changes in patients with chronic
      stable angina.

PMID- 11310379
TI  - Protein intake in Indian haemodialysis patients.
AB  - OBJECTIVES: Aim of our study was to find out the amount of protein consumed by
      Indian haemodialysis patients. METHODS: Twenty patients with endstage renal
      disease on regular haemodialysis at a major urban dialysis centre in India had
      their Kt/V and nPCR measured monthly for 4 months utilising urea kinetic methods.
      RESULTS: Despite an adequate amount of dialysis per session being delivered to
      almost all of these patients (19 out of 20 had a Kt/V greater than 1.2) none of
      our patients had an nPCR greater than 1 gm/kg/day and only 4 patients i.e. 20%
      had a protein intake greater than 0.8 gm/kg/day which is a cut off point below
      which mortality has been shown to increase dramatically. Most of the patients had
      a protein intake between 0.7-0.8 gm/kg/day which is alarmingly low. Patients who
      consumed non vegetarian food at least thrice a week did appear to have a
      significantly higher protein intake compared to the rest of the patients.
      CONCLUSION: We believe that these results are likely to be representative of
      other dialysis centers in India and that an intensive effort at dietary education
      aimed at increasing the protein intake in our haemodialysis patients is urgently
      required. The morbidity and mortality of dialysis patients is high and perhaps
      appropriate dietary intervention can help to reduce this.

PMID- 11310380
TI  - Tropical pyomyositis: experience of a tertiary care hospital in north-west India.
AB  - OBJECTIVE: Tropical pyomyositis (TP), a disease of varied aetiology, has been
      reported frequently from Africa and Latin America. However there are only a few
      reports from India. MATERIAL AND METHODS: Between January 1992 to June 1999, 26
      patients with TP were admitted to Post Graduate Institute of Medical Education
      and Research Chandigarh, a tertiary care centre in north-west India and formed
      the study material. RESULTS: The disease was more common in young adults with
      male to female ratio being 5:2. In majority, presenting features were muscle
      pains (100%) and fever (81%). The diagnosis was confirmed by aspirating pus from
      the involved muscle. The pus grew organisms in 41.7% patients and methicillin
      sensitive Staphylococcus aureus was the commonest causative organism. Blood
      cultures were positive in 14.3% of cases. The common complications were
      bronchopneumonia (23.1%), empyema (19.2%) and venous thrombosis (15.4%). In three
      patients, the disease occurred in association with tuberculosis of dorsal-lumbar
      spine. The overall mortality was low (7.7%). CONCLUSIONS: TP is not an uncommon
      disease in India. Though the presenting features were similar to earlier studies,
      complications varied and mortality was low. An early recognition and aggressive
      treatment helps in decreasing morbidity and mortality.

PMID- 11310381
TI  - A randomised controlled trial of intradermal hepatitis B vaccination and
      augmentation of response with erythropoietin.
AB  - AIM: Intradermal administration of Hepatitis B vaccine (HBV) achieves better
      seroconversion in patients on dialysis compared to intramuscular administration.
      The aim of the study was to determine whether twice weekly intradermal injections
      of the vaccine can further augment the vaccine response as compared to once
      weekly injections. Patients with end stage renal failure on haemodialysis were
      randomly allocated over a period of 22 months to receive 20 mu gms of recombinant
      HBV by intradermal injections once a week (group 1) or twice a week (group 2) for
      6 weeks. The patients recruited during the first 12 months of the study did not
      receive recombinant human erythropoietin (Epo) as it was not available (phase 1).
      During the last 10 months of study all patients received Epo (phase 2) in
      addition to HBV. RESULTS: A total of 85 patients were enrolled of whom 77
      completed the study. There were 41 patients in group 1 and 36 patients in group
      2. Seroprotection (anti HBs > 10 mIU/ml in the absence of HBs Ag and anti HBc)
      was achieved in 56.1% patients of group I compared to 77.8% of group 2 (p <
      0.05). The seroprotection rate was 78.1% among patients receiving Epo (phase 2)
      compared to 60% among 45 who did not receive Epo (phase 1). Anti HBs titre in
      responders was 308.5 +/- 148.7 mIU/ml in patients of phase 2 compared to 198 +/-
      112.8 mIU/ml in patients of phase 1 (p < 0.05). The subgroup receiving both Epo
      and twice weekly vaccine (group 2 of phase 2) had the highest seroprotection rate
      of 86.7%. CONCLUSION: Twice weekly intradermal vaccination is more effective than
      once weekly regime in achieving rapid seroconversion. The vaccine response may be
      augmented by use of Epo probably due to reduction in transfusion requirement and
      concomitant immunosuppression.

PMID- 11310382
TI  - Role of autoimmunity in nonviral chronic liver disease.
AB  - OBJECTIVE: To evaluate the prevalence and clinical profile of autoimmune
      hepatitis (AIH) in patients with chronic liver disease. METHODS: Four hundred and
      thirty five consecutive patient with chronic liver disease seen in our department
      from January 1997 to December 1998 were studied with detailed history and
      clinical examination. All the patients underwent liver function tests,
      ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA,
      ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever
      permissible. Appropriate work up for Wilson's disease was done whenever suspected
      clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring
      system by international autoimmune hepatitis group. Twenty out of the 435
      patients met the criteria of definite autoimmune hepatitis and seven patient had
      probable autoimmune hepatitis. Forty out of 408 patients showed markers of
      autoimmunity positive but did not qualify diagnosis of AIH on composite scores.
      RESULTS: Demographic profile of 27 patients with autoimmune hepatitis was as
      follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years);
      mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%)
      and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12
      (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and
      262 +/- 418 respectively. Other disease associations seen were as follows:
      diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2
      (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was
      ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children),
      ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA
      in tires less than 1:80 was found in 3 patients. Liver histology changes seen
      were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell
      rossetting (80%) and fibrosis with or without cirrhosis (50%). CONCLUSION:
      Autoimmune liver disease is not uncommon in India and should be suspected in all
      patients with chronic liver disease, especially in non-viral, non-alcoholic,
      female patients. The diagnosis of AIH should however be made on the composite
      scoring system given by international group and not only on the presence or
      absence of autoimmune markers.

PMID- 11310383
TI  - Nosocomial pneumonia in medical intensive care unit.
AB  - OBJECTIVES: This study was undertaken to determine incidence, clinical features,
      microbiological flora and prognosis of patients with nosocomial pneumonia (NP) in
      medical intensive care unit (ICU). Also to study impact of comorbid illnesses,
      intubation and mechanical ventilation on outcome. METHODS: In this prospective
      study over a period of one year 89 patients were detected to have nosocomial
      pneumonia amongst 948 total admissions in ICU. All these 89 patients were
      investigated radiologically, microbiologically and biochemically. Mortality in
      these patients was correlated with various factors using chi-square test.
      RESULTS: Incidence of NP was 9.38%. Enteric gram-negative organisms were
      commonest isolates (61.9%), followed by Staph aureus (29.8%). Sixty five (73%)
      patients had severe pneumonia, 47 (52.8%) required intubation and 42 (47.2%)
      mechanical ventilation. Total mortality was 19 out of 89 (21.3%). High mortality
      was associated with habits like smoking (33.3%), age group over 60 years (27.3%),
      presence of comorbid illness like DM and COAD (38.5%), complications like ARDS
      (61.3%, p < 0.001) or sepsis with end organ failure (73.7%, p < 0.001) and need
      of intubation (36.2%) or mechanical ventilation (40.5%, p < 0.005). CONCLUSION:
      Nosocomial pneumonias constitute important problem in medical ICU and are
      associated with high mortality. Patients with advanced age, co-morbid illness,
      ARDS and end organ failure are at high risk for mortality. However with intensive
      supportive care and appropriate antibiotics many such lives can be saved.

PMID- 11310384
TI  - Troponin-T in unstable angina--a clinical and angiographic study.
AB  - OBJECTIVE: To examine the prognostic significance of Troponin-T in patients
      admitted with unstable angina and to study their angiographic morphology. DESIGN:
      Single centre, prospective study of in hospital events. SETTING: Intensive
      coronary care unit of a large municipal general hospital. SUBJECTS: 128
      consecutive patients admitted with a diagnosis of unstable angina (Braunwald's
      classification). METHODS: Measurement of Troponin-T by qualitative assay at
      admission, coronary angiography between 5th to 7th day. MAIN OUTCOME MEASURES: In
      hospital adverse cardiac events--recurrent angina, new myocardial infarction or
      cardiac deaths. RESULTS: Fifty six (43.7%) patients had a positive test. The
      incidence of recurrent angina was significantly higher in the Trop-T positive
      group (57.1% vs 11.1%, p < 0.001). Six patients of this developed acute
      myocardial infarction subsequently whereas none of the patients in the Trop-T
      negative group developed acute MI (10.7% v/s 0%, p = 0.05). There were two deaths
      in the Trop-T positive group and none in the Trop-T negative group. 44 (78.5%)
      patients of the Trop-T positive group and 60 patients in the Trop-T negative
      group underwent coronary angiography. There was no significant difference in the
      incidence of single vessel disease (27.2% v/s 20%, p = NS) or multivessel disease
      (72.7% v/s 69.9%, p = ns). None of the patients with a positive Trop-T had normal
      coronary angiography whereas 6 patients in the Trop-T negative group had a normal
      coronary angiography (0% v/s 10%, p < 0.05). Patients with a positive troponin T
      test had a significantly higher incidence of type B lesions and a higher
      incidence of intracoronary thrombus. CONCLUSIONS: The in hospital outcome of Trop
      T positive patients was significantly worse than patients with a negative test.
      Patients with a positive troponin T test had more complex coronary morphology and
      a higher incidence of intracoronary thrombus. We conclude that troponin-T can be
      used as a prognostic marker in patients with unstable angina.

PMID- 11310385
TI  - The role of dietary protein restriction in Indian patients with chronic renal
      failure.
AB  - OBJECTIVE: To determine dietary protein intake in Indian patients with chronic
      renal failure and the impact of prescribing protein restricted diets to these
      patients. METHODS: Baseline dietary protein intake was estimated in forty five
      patients with chronic renal failure on an unrestricted diet. Of these 45
      patients, 27 were vegetarian and 18 were non-vegetarian. Then the patients were
      divided into 2 comparable groups. Twenty group I patients were allowed to
      continue unrestricted diet while 25 group II patients were advised 0.6 g/kg/day
      (50% high biological value) protein. Protein intake was estimated at 1 and 2
      month follow up. RESULTS: The baseline dietary protein intake in 45 patients was
      0.65 +/- 0.15 (mean +/- 1 SD) g/kg/day. There was no significant difference in
      protein intake of group I and group II patients at 1 and 2 month follow up. Also,
      the protein intake in group II patients was not different at 1 and 2 month follow
      up compared to baseline value. CONCLUSION: Protein intake of Indian patients with
      CRF is usually low even on an unrestricted diet. The usual practice of advising
      dietary protein restriction has no significant impact on the protein intake.

PMID- 11310386
TI  - Hemoglobin E disorders in the north east India.
AB  - Clinical and hematological features of nine cases of Hemoglobin E variant were
      studied prospectively over three years. There were three cases of HbE-beta
      thalassemia and six cases of homozygous HbE disease. Two cases were asymptomatic.
      The commonest symptom was jaundice (unconjugated 2). Other symptoms were left
      hypochondrial pain, tiredness, syncope and failure to thrive. Splenomegaly and
      microcytosis was detected in all. Mild anaemia was present in majority (6/9), and
      the mean hemoglobin was 11.3 gm/dl. Reticulocyte count was normal in all and
      cholelithiasis was seen in one patient only. Clinical and hematological features
      were evaluated and compared to reported series. Splenomegaly was found to be more
      common.

PMID- 11310387
TI  - Relapse pattern of Plasmodium vivax in Mumbai: a study of 283 cases of vivax
      malaria.
AB  - OBJECTIVES: To analyze the relapse pattern of Plasmodium vivax in the city of
      Mumbai. METHODS: 283 cases of smear positive vivax malaria were treated with full
      dose (25 mg/kg) chloroquine and were asked to follow up for at least one year.
      None of the patients received primaquine. RESULTS: Of the 150 cases who followed
      up for at least one year, 19 relapsed, 17/19 relapsed within the first 6 months;
      indicating that the relapse pattern in the city is predominantly of the tropical
      or Chesson strain type. CONCLUSIONS: Vivax malaria patients should be monitored
      for at least six months. Those who do relapse should receive treatment with full
      dose chloroquine and 14 days of primaquine treatment.

PMID- 11310388
TI  - Disseminated cysticercosis.

PMID- 11310389
TI  - Evaluation of a short course on diabetology for practising doctors.
AB  - A short course on Diabetology, attended by 83 doctors was evaluated. The doctors
      were divided into three groups. (Group I--basic qualification MBBS, Group II--MD
      in medicine or allied subject, Group III--Diploma in Diabetes Mellitus). The mean
      age group of all three groups were comparable. Pre-course evaluation of their
      knowledge of diabetes showed the best performance in Group III and poorest in
      Group I. Post-course evaluation showed significant improvement only in Group I
      and II. Maximal improvement in performance was seen in Group II. Mean time since
      passing the last professional examination was 14.8, 12.6 and 1.0 year
      respectively. The performance was not linked to time since passing the last
      examination. 14.5% of doctors were from a rural or semiurban setting. The
      precourse performance of rural doctors in the MD group was significantly poorer,
      but their post course performance was as good as the others. All doctors from
      rural or semiurban areas improved their performance postcourse, compared to 84%
      in the urban group. 74% of doctors had not attended any post graduate course
      after their basic degree. Their performance did not differ significantly from
      those who had attended such courses. 44.6% were Consultants, 26.6% were general
      practitioners, 12.0% were attached to institutions, 10.8% were in government
      service or armed forces and 6% were attached to teaching hospitals. The
      performance of the doctors was not linked to the type of practice. The doctors
      attending the course felt that the audiovisual presentation needed improvement.

PMID- 11310390
TI  - Potential and novel therapies for asthma.
AB  - Asthma is a chronic inflammatory disorder characterised by airflow obstruction.
      The inflammatory process involves mast cells, antigen presenting cells,
      eosinophils, neutrophils, airway epithelial cells and TH2 lymphocytes. These
      cells produce a broad array of pro-inflammatory mediators and cytokines that lead
      to the pathophysiological changes seen in asthma. The improved understanding of
      this complex disease, the specific cells and the complex mediators has lead to
      newer insights into the efficacy of various novel and potential therapies. In
      this review, we discuss the pharmacological agents that interrupt the synthesis
      and action of leukotrienes, cytokine antagonism, monoclonal antibodies against
      IgEs, selective phosphodiesterase inhibitors, adenosine receptor ligands and
      immunomodulators to drive the inflammatory response towards a TH1 type and other
      possible specific targeted therapy for the management of asthma. Although most of
      these therapies are in the inchoate stages these may hold the future for use in
      asthma.

PMID- 11310391
TI  - Discrete subvalvular aortic stenosis.
AB  - Discrete Subaortic Stenosis is one of the many lesions responsible for left
      ventricular outflow tract (LVOT) obstruction. It may present as in an isolated
      from as membranous or fibromuscular ring below the aortic valve or in association
      with other congenital anamolies such as VSD, PDA, coarctation of aorta,
      hypoplastic aortic annulus, double chamber right ventricle among others. The
      condition is rarely diagnosed antenataly or in infancy but often manifests in the
      first decade of life with features of progressive LVOT obstruction, LV
      hypertrophy and dysfunction aortic regurgitation due to damage to the aortic
      cusps because of the jet from the subaortic narrowing which may also render the
      aortic valve prone to infective endocarditis. Interaction of genetic
      predisposition and morphologically deformed long and narrow LVOT cause
      rheological abnormalities and increased shear stress in the region of subaortic
      stenosis and seem to be the main etiological factor alongwith poorly defined role
      of more extensive but subtle changes in the LV endocardium. Condition can be
      easily diagnosed by cross-sectional and Doppler echocardiography and confirmed by
      demonstrating a pressure gradient below aortic valve on cardiac catheterisation
      and LV angiography. Surgical membranectomy alongwith myotomy or myomectomy remain
      the mainstay of treatment but long term results are not satisfactory as there is
      a high rate of recurrences requiring reoperations. A close follow up with serial
      echocardiographic examinations is very helpful in early detection of subaortic
      obstruction in patients who have so called functional murmurs in the childhood.

PMID- 11310392
TI  - Cranial irradiation--an unusual cause for diabetes insipidus.
AB  - Central diabetes insipidus frequently occurs due to tumours in the region of
      pituitary or hypothalamus or following surgical trauma to these regions. Rarely
      it has been reported following cranial irradiation. We report the case of a
      middle aged woman who underwent surgical removal of a frontal capillary
      hemangioblastoma and received cranial irradiation. She presented ten months later
      with features of diabetes insipidus which was confirmed to be of central origin.
      She responded well to desmopressin nasal spray. Radiation induced damage to the
      hypothalmo-pituitary axis presents usually with anterior pituitary hormone
      deficiencies, most commonly that of growth hormone. Presentation as central
      diabetes insipidus is very uncommon.

PMID- 11310393
TI  - Snake bite presenting as acute myocardial infarction, ischaemic cerebrovascular
      accident, acute renal failure and disseminated intravascular coagulopathy.
AB  - An unusual presentation of a viperine snake bite presenting with ischaemic damage
      to the major organs like brain and heart leading to cerebrovascular accident and
      acute myocardial infarction along with acute renal failure and disseminated
      intravascular coagulopathy (DIC) is described in this report.

PMID- 11310394
TI  - Acquired immunodeficiency syndrome presenting as testicular tuberculosis.
AB  - A 50 year old heterosexual male presented with fever and cough with expectoration
      of months duration, and swelling in the right testis. The serological tests
      showed positivity for HIV 1 and 11 antibodies. Testicular biopsy from the right
      testis showed epitheloid cell granulomas with central caseous necrosis and
      peripheral mantle of lymphocytes and plasma cells. Zeihl-Neelsen stain on tissue
      sections showed AFB positivity. To the best of our knowledge this is the  second
      reported case of acquired immunodeficiency syndrome presenting as testicular
      tuberculosis.

PMID- 11310395
TI  - 99mTc-Sestamibi scan in a patient with an ectopic parathyroid adenoma.

PMID- 11310396
TI  - Cronkhite Canada syndrome.
AB  - Cronkhite Canada syndrome is an acquired non-familial syndrome characterised by
      diffuse gastrointestinal polyposis with alopecia nail dystrophy and
      hyperpigmentation. There is chronic diarrhoea and protein losing enteropathy. The
      etiology of this syndrome remains obscure. The rarity of the case prompts this
      case report.

PMID- 11310397
TI  - Cockayne syndrome.
AB  - We report four cases of Cockayne Syndrome in a family of seven children. Apart
      from the usual clinical and laboratory features, sparse eye lashes and high
      arched palate in two patients, conjunctival and corneal edema in one, and
      proximal muscle weakness in one patient were noticed as additional findings.

PMID- 11310398
TI  - Risperidone induced cytopenias.

PMID- 11310399
TI  - Segmental neurofibromatosis with agenesis of corpus callosum.

PMID- 11310400
TI  - Primary midbrain hemorrhage presenting as Parinaud's syndrome.

PMID- 11310401
TI  - Hemiplegia in a patient with fibrocalculous pancreatic diabetes.

PMID- 11310402
TI  - A preliminary trial of serratiopeptidase in patients with carpal tunnel Syndrome.

PMID- 11310403
TI  - Lipoprotein (a) and coronary heart diseases in Indian population.

PMID- 11310404
TI  - Exercise induced changes in QT dispersion before and after coronary angioplasty.

PMID- 11310405
TI  - Safety and immunogenicity of an r-DNA hepatitis B vaccine (Hepavax-gene) in
      healthy Indian adults.

PMID- 11310406
TI  - Epidemiological studies in developing countries.

PMID- 11310407
TI  - Tuberculous peritonitis--an uncommon presentation.

PMID- 11310408
TI  - Tuberculous mediastinal adenopathy presenting as dysphagia.

PMID- 11310409
TI  - Bioethics at century's turn: Can normative ethics be retrieved?

PMID- 11310410
TI  - Why has bioethics become so boring?

PMID- 11310411
TI  - Growth regulation, acid sphingomyelinase gene and genomic imprinting: lessons
      from an experiment of nature.
AB  - The author investigated the possible role of acid sphingomyelinase (ASM) gene
      (SMPD1) in the regulation of growth, in connection with an experiment of nature.
      The association of a decreased ASM activity and an overgrowth disorder, Beckwith
      Wiedemann Syndrome (BWS) with hemihypertrophy has been described at a 23 months
      old boy in a recent case report (Rethy et al, in this issue). ASM catalyses the
      production of ceramide, a key molecule of apoptosis, from sphingomyelin. Based on
      these data it is suggested that the ASM gene (SMPD1) can suppress/counterbalance
      the anti-apoptotic effects of BWSrelated growth-promoters, like IGF-II, under
      normal circumstances. Recent literary data support this view. ASM deficient
      lymphoblasts derived from patients with Niemann-Pick disease (NPD) fail to
      undergo apoptosis in response to external signals and Fas cross-linking. BWS
      related genes are considered to be regulated by genomic imprinting. Therefore the
      author compared some characteristics of both SMPD1 and imprinted genes. The
      analyzed features of SMPD1 gene (few and small introns, Alu 1 repeat element, CC
      rich regulatory region, alternative splicing) are characteristic to imprinted
      genes. Hemihypertrophy, mentioned in the referred BWS-case, is distinctive to the
      involvement of the maternal allele of the second BWS chromosomal region (BWSCR2)
      at 11p15.3. The SMPDI gene has been localized just distal to the B05 breakpoint
      of BWSCR2. Furthermore, in BWS-associated tumors, the loss of heterozygosity
      (LOH) found on 11p15 was always maternal. Thus, in the case referred to with ASM
      deficiency the maternal allele has certainly been effected. These conclusions are
      in accordance with the 'cluster-model of imprinting' as well as with the conflict
      theory of imprinting. Taken together, the above mentioned clinical and
      experimental data suggest that SMPD1, most likely at 11p15.4, is an imprinted,
      maternally expressed, BWS- and apoptosis-related growth suppressor gene. Further
      studies are necessary to prove this hypothesis.

PMID- 11310412
TI  - Breastfeeding rates in New Zealand.

PMID- 11310413
TI  - Misoprostol and uterine rupture.

PMID- 11310414
TI  - Caveat emptor: editors beware.

PMID- 11310415
TI  - Physical activity and cancer risk.
AB  - Evidence is accumulating that high levels of physical activity are associated
      with a reduced risk of some cancers. This evidence is most consistent for colon
      cancer, which is reduced by 40-50% among the most active individuals, compared
      with the least active. The effect is evident in men and women, and appears to be
      independent of important confounding factors. However, there may be important
      interactions with body fatness; a high BMI has been reported to be associated
      with an increased risk of colon cancer in sedentary men but not in physically
      active men. Whilst the evidence on breast cancer is less consistent, case-control
      studies typically suggest a reduction of 25-30% among the most active women,
      although several studies have found no effect. Potential mechanisms include
      systemic influences and others relevant only to site-specific cancers. One
      unifying hypothesis is that physical inactivity reduces insulin sensitivity,
      leading to a growth-promotional environment which may facilitate neoplasia. The
      non-specific immune system may be improved by physical activity, possibly through
      the summative effects of repeated exercise bouts. Regular exercise, even at a
      recreational level, probably reduces exposure to oestrogen and thus decreases the
      risk of breast cancer. Increased colonic peristalsis, and thus reduced bowel
      transit time, might partly explain the lower risk of colon cancer in active
      people. Physical activity emerges as one of the few modifiable risk factors for
      some cancers and, as such, justifies further study.

PMID- 11310416
TI  - Consequences of genetic change in farm animals on food intake and feeding
      behaviour.
AB  - Selection in commercial populations on aspects of output, such as for growth rate
      in poultry. against fatness and for growth rate in pigs, and for milk yield in
      cows, has had very barge effects on such outputs over the past 50 years. Partly
      because of the cost of recording intake, there has been little or no selection
      for food intake or feeding behaviour. In order to predict the effects of such
      past, and future, selection on intake it is necessary to have some suitable
      theoretical framework. Intake needs to be predicted in order to make rational
      feeding and environmental decisions. The idea that an animal will eat 'to meet
      its requirements' has proved useful and continues to be fruitful. An important
      part of the idea is that the animal (genotype) can be described in a way that is
      sufficient for the accurate prediction of its outputs over time. Such
      descriptions can be combined with a set of nutritional constants to calculate
      requirements. There appears to have been no change in the nutritional constants
      under selection for output. Under such selection it is simplest to assume that
      changes in intake follow from the changes in output rates, so that intake changes
      become entirely predictable. It is suggested that other ways that have been
      proposed for predicting intake cannot be successful in predicting the effects of
      selection. Feeding behaviour is seen as being the means that the animal uses to
      attain its intake rather than being the means by which that intake can be
      predicted. Thus, the organisation of feeding behaviour can be used to predict
      neither intake nor the effects of selection on it.

PMID- 11310417
TI  - The regulation of body weight: lessons from the seasonal animal.
AB  - The hypothalamus is a major regulatory centre involved in the control of many
      important physiological axes. One of these axes is the regulation of ingestive
      behaviour. Recent work using a combination of genetic-mutant mouse models
      together with targeted gene deletions has contributed much to our understanding
      of how neural pathways of the hypothalamus are involved in the regulation of
      energy balance in animals. These pathways are also relevant to human energy
      homeostasis. as mutations in key genes are correlated with obesity. Many of the
      genes identified mediate the effects of leptin, and are therefore primarily
      involved in sensing and responding to peripheral signals. In seasonal animals,
      such as the Siberian hamster (Phodopus sungorus), there is evidence for a higher
      level of regulation. The systems involved regulate body weight around an apparent
      'set-point' through the action of photoperiod via the neurohormone, melatonin.
      The ability to manipulate energy balance through photoperiod (and melatonin) in
      the seasonal-animal model offers novel opportunities to identify further
      fundamental aspects of the control mechanisms involved in the central control of
      energy homeostasis and body weight.

PMID- 11310418
TI  - The biology of amino acid requirements: what do they mean and can we measure
      them?

PMID- 11310419
TI  - A healthy body, a healthy mind: long-term impact of diet on mood and cognitive
      function.
AB  - Certain dietary risk factors for physical ill health are also risk factors for
      depression and cognitive impairment. Although cholesterol lowering has been
      suggested to increase vulnerability to depression, there is better support for an
      alternative hypothesis that intake of n-3 long-chain polyunsaturated fatty acids
      can affect mood (and aggression). Possible mechanisms for such effects include
      modification of neuronal cell membrane fluidity and consequent impact on
      neurotransmitter function. Stronger evidence exists concerning a role for diet in
      influencing cognitive impairment and cognitive decline in older age, in
      particular through its impact on vascular disease. For example, cognitive
      impairment is associated with atherosclerosis, type 2 diabetes and hypertension,
      and findings from a broad range of studies show significant relationships between
      cognitive function and intakes of various nutrients, including long-chain
      polyunsaturated fatty acids, antioxidant vitamins, and folate and vitamin B12.
      Further support is provided by data on nutrient status and cognitive function.
      Almost all this evidence, however, comes from epidemiological and correlational
      studies. Given the problem of separating cause and effect from such evidence, and
      the fact that cognitive impairment and cognitive decline (and depression) are
      very likely to be significant factors contributing to the consumption of a poor
      diet, greater emphasis should now be placed on conducting intervention studies.
      An efficient approach to this problem could be to include assessments of mood and
      cognitive function as outcome measures in studies designed primarily to
      investigate the impact of dietary interventions on markers of physical health.

PMID- 11310420
TI  - Theoretical developments in the study and prediction of food intake.
AB  - The purpose of the present paper is to review recent theoretical developments in
      food intake modelling applied to animal science and ecology. The models are
      divided into those that have been developed for intensive agricultural systems,
      and those which consider more extensive systems and natural systems. For the most
      part the present paper discusses models that predict the food intake of
      herbivores. The mechanisms of each model are discussed, along with a brief
      mention of the experimental support for the most popular models. We include a
      discussion of models that approach the study of food intake behaviour from an
      evolutionary perspective, and suggest that lifetime models are especially useful
      when food intake carries an intrinsic cost. These long timescale evolutionary
      models contrast with the more common food intake models, whose timescale is
      usually much shorter. We conclude that the 'eating to requirements' model
      highlights an important food intake mechanism that provides an accurate
      predictive tool for intensive agricultural systems. The mechanisms of food intake
      regulation in extensive systems are less certain, and closer links between the
      ideas of animal science and ecology will be helpful for improving our
      understanding of food intake regulation.

PMID- 11310421
TI  - Challenges for meeting the global food and nutrient needs in the new millennium.
AB  - Major advances have occurred in food production during the last 30 years as a
      result of the adoption of green revolution technology. The price of rice and
      wheat is 40 % lower than it was in the 1950s. This lower price has helped the
      poorer sections of society, who spend 50-60% of their income on food. The
      proportion of the population in the developing world that is malnourished fell
      from 46.5% in the early 1960s to 31% in 1995. However, there are still 1.3
      billion of the population who go to bed hungry every day. Deficiencies of
      micronutrients such as Fe, Zn and vitamin A affect millions of the population in
      the developing world. The world population is increasing at the rate of 1.4%, or
      an increase of eighty million per year. It is estimated that we will have to
      produce 50% more food grains by 2025. Various strategies for meeting this
      challenge exist, including the development of cereal varieties with a higher
      yield potential and yield stability, and farmer-friendly public policies. In
      order to tackle hidden hunger, efforts are underway to develop crop varieties
      with higher concentrations of Fe and Zn. Recently, a breakthrough has occurred in
      the introduction of the genes for the pathway leading to the biosynthesis of beta
      carotene, a precursor of vitamin A, in rice. Various conventional approaches and
      modem tools of biotechnology are being employed in the development of crop
      varieties with higher yields and higher levels of micronutrients.

PMID- 11310422
TI  - Metabolism 2000: the emperor needs new clothes.
AB  - Metabolism is one of the corner stones of nutritional science. As biology enters
      the post-genomic era and with functional genomics beginning to takeoff, we
      anticipate that the study of metabolism will play an increasingly important role
      in helping to link advances made via the reductionist paradigm, that has been so
      successful in molecular and cellular biology, with those emerging from
      observational studies in animals and human subjects. A reconstructive
      metabolically-focused approach offers a timely paradigm for enhancing the
      elegance of nutritional science. Here we give particular attention to the use of
      tracers as phenotyping tools and discuss the application of our metaprobe
      concepts with respect to some novel features of metabolism, including
      'underground metabolism', 'metabolic hijacking', 'catalytic promiscuity' and
      'moonlighting proteins'. The opportunities for enhancing the study of metabolism
      by new and emerging technologies, and the importance of the interdisciplinary
      research enterprise are also touched upon. We conclude that: (1) the metaprobe
      concepts and approach, discussed herein, potentially yield a quantitative
      physiological (metabolic) phenotype against which to elaborate partial or focused
      genotypes; (2) physiological (metabolic) phenotypes which have a whole-body or
      kinetically-discernible inter-organ tissue-directed metabolic signature are an
      ideal target for this directed tracer-based definition of the 'functional'
      genotype; (3) metabolism, probed with tracer tool kits suitable for measuring
      rates of turnover, change and conversion, becomes in the current sociology of the
      'Net', like AOL, Yahoo. Alta Vista, Lycos or Ask Jeeves, the portal for an
      exploration of the metabolic characteristics of the 'Genomics Internet'.

PMID- 11310423
TI  - The relative contribution of diet and genotype to bone development.
AB  - The present review addresses the relative contribution of diet and genotype to
      variability in human bone growth and mineralisation in the context of the
      aetiology of osteoporosis. Heritability studies indicate that 60-70 % of the
      variability in bone mineral mass or bone mineral density (BMD) can be accounted
      for by genetic variation. Cross-trait analyses suggest that a proportion of this
      variation reflects genetic influences on bone and body size, such as height and
      lean body mass. Candidate-gene studies have demonstrated associations between
      several genetic polymorphisms and bone mineral mass but, as yet, genotype
      determinations have proved unhelpful in identifying individuals at increased risk
      of osteoporosis. Variations in diet and other environmental factors contribute 30
      40 % to total phenotypic variance in bone mineral mass or BMD. Correlations
      between intakes of individual nutrients and BMD have been reported, but these
      relationships are subject to confounding due to size. However, no specific
      dietary factor has been identified from prospective and twin studies as making a
      significant contribution to environmental variability in BMD or bone loss. This
      finding may reflect the difficulties in quantifying environmental exposures. both
      current and over a lifetime. In addition, the influence of diet on bone health
      may depend on the genotype of the individual. Optimisation of nutrition and
      lifestyle remains an attractive strategy for the reduction of fracture risk, but
      more research is required to fully define optimal dietary requirements.

PMID- 11310424
TI  - Genes, folate and homocysteine in embryonic development.
AB  - Population-based studies of human pregnancies show that periconceptional folate
      supplementation has a significant protective effect for embryos during early
      development, resulting in a significant reduction in developmental defects of the
      face, the neural tube, and the cono-truncal region of the heart. These results
      have been supported by experiments with animal models. An obvious quality held in
      common by these three anatomical regions is that the normal development of each
      region depends on a set of multi-potent cells that originate in the mid-dorsal
      region of the neural epithelium. However, the reason for the sensitive dependence
      of these particular cells on folic acid for normal development has not been
      obvious, and there is no consensus about the biological basis of the dramatic
      rescue with periconceptional folate supplementation. There are two principal
      hypotheses for the impact of folate insufficiency on development; each of these
      hypotheses has a micronutrient component and a genetic component. In the first
      hypothesis the effect of low folate is direct, limiting the availability of folic
      acid to cells within the embryo itself; thus compromising normal function and
      limiting proliferation. The second hypothetical effect is indirect; low folate
      disrupts methionine metabolism; homocysteine increases in the maternal serum;
      homocysteine induces abnormal development by inhibiting the function of N-methyl
      D-aspartate (NMDA) receptors in the neural epithelium. There are three general
      families of genes whose level of expression may need to be considered in the
      context of these two related hypotheses: folate-receptor genes; genes that
      regulate methionine-homocysteine metabolism; NMDA-receptor genes.

PMID- 11310425
TI  - Nutrition-hormone receptor-gene interactions: implications for development and
      disease.
AB  - Nutrition profoundly alters the phenotypic expression of a given genotype,
      particularly during fetal and postnatal development. Many hormones act as
      nutritional signals and their receptors play a key role in mediating the effects
      of nutrition on numerous genes involved in differentiation, growth and
      metabolism. Polypeptide hormones act on membrane-bound receptors to trigger gene
      transcription via complex intracellular signalling pathways. By contrast, nuclear
      receptors for lipid-soluble molecules such as glucocorticoids (GC) and thyroid
      hormones (TH) directly regulate transcription via DNA binding and chromatin
      remodelling. Nuclear hormone receptors are members of a large superfamily of
      transcriptional regulators with the ability to activate or repress many genes
      involved in development and disease. Nutrition influences not only hormone
      synthesis and metabolism but also hormone receptors, and regulation is mediated
      either by specific nutrients or by energy status. Recent studies on the role of
      early environment on development have implicated GC and their receptors in the
      programming of adult disease. Intrauterine growth restriction and postnatal
      undernutrition also induce striking differences in TH-receptor isoforms in
      functionally-distinct muscles, with critical implications for gene transcription
      of myosin isoforms. glucose transporters, uncoupling proteins and cation pumps.
      Such findings highlight a mechanism by which nutritional status can influence
      normal development, and modify nutrient utilization. thermogenesis. peripheral
      sensitivity to insulin and optimal cardiac function. Diet and stage of
      development will also influence the transcriptional activity of drugs acting as
      ligands for nuclear receptors. Potential interactions between nuclear receptors,
      including those for retinoic acid and vitamin D, should not be overlooked in
      intervention programmes using I or vitamin A supplementation of young and adult
      human populations

PMID- 11310426
TI  - Iron deficiency and iron overload: effects of diet and genes.
AB  - Like most essential nutrients, Fe needs to be maintained in the body at a defined
      level for optimal health, with appropriate adaptation to varying Fe needs and
      supply. The primary mechanism for controlling Fe level is the regulation of Fe
      absorption. Several different proteins have been identified as contributors to
      the process. Despite a complex regulatory system, Fe disorders (both Fe
      deficiency and Fe overload) occur. Fe deficiency is a common problem worldwide,
      resulting from inadequate dietary Fe and blood loss. Complications include pre
      term labour, developmental delay, and impaired work efficiency. No specific
      genetic syndromes causing isolated Fe deficiency have been described, but animal
      studies and clinical observations suggest that such a relationship may be a
      possibility. Conversely, the known causes of Fe overload are genetic. Fe overload
      is less common than Fe deficiency, but can result in serious medical
      complications, including cirrhosis, primary liver cancer, diabetes,
      cardiomyopathy and arthritis. The most common and best characterized syndrome of
      Fe overload is hereditary haemochromatosis (HHC), an autosomal recessive
      disorder. Mutations in the HFE protein cause HHC, but the clinical presentation
      is variable. Of particular interest is the factor that some FIFE genotypes appear
      to be associated with protection from Fe deficiency. Other genetic variants in
      the regulatory pathway may influence the likelihood of Fe deficiency and Fe
      overload. Studies of genetic variants in HFE and other regulatory proteins
      provide important tools for studying the biological processes in Fe regulation.
      This work is likely to lead to new insights into Fe disorders and potentially to
      new therapeutic approaches. It will not be complete, however, until coordinated
      study of both genetic and nutritional factors is undertaken.

PMID- 11310427
TI  - Energy balance and cancer: the role of sex hormones.
AB  - Energy balance can affect the risk for hormone-related cancers by altering sex
      hormone levels. Energy intake and expenditure are difficult to measure in
      epidemiological studies, but a chronic excess of intake relative to expenditure
      leads to a high BMI, which can be accurately measured. In premenopausal women
      obesity has little effect on the serum concentration of oestradiol, but causes an
      increase in the frequency of anovular menstrual cycles and thus a reduction in
      progesterone levels; these changes lead to a large increase in the risk for
      endometrial cancer. but little change, or a small decrease, in the risk for
      breast cancer. In post-menopausal women oestradiol levels are not regulated by
      negative feedback, and obesity causes an increase in the serum concentration of
      bioavailable oestradiol; this factor causes increases in the risk for both
      endometrial cancer and breast cancer. The development of ovarian cancer appears
      to be related more strongly to the frequency of ovulation than to direct effects
      of circulating levels of sex hormones, and BMI is not clearly associated with the
      risk for ovarian cancer. In men, increasing BMI has little effect on bioavailable
      androgen levels, and any effect of obesity on prostate cancer risk is small.

PMID- 11310429
TI  - International Federation of Gynecology and Obstetrics (FIGO) constituent
      societies.

PMID- 11310428
TI  - Energy balance and cancer: the role of insulin and insulin-like growth factor-I.
AB  - Recent theories propose that a Western lifestyle may increase cancer risk through
      alterations in the metabolism of insulin and insulin-like growth factors (IGF:
      McKeown-Eyssen, 1994; Giovannucci, 1995; Kaaks, 19%; Werner & LeRoith, 1996).
      Insulin regulates energy metabolism, and increases the bioactivity of IGF-I, by
      enhancing its synthesis. and by decreasing several of its binding proteins
      (IGFBP; IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic processes as a
      function of available energy and elementary substrates (e.g. amino acids). The
      anabolic signals by insulin or IGF-I can promote tumour development by inhibiting
      apoptosis, and by stimulating cell proliferation. Furthermore, both insulin and
      IGF-I stimulate the synthesis of sex steroids, and inhibit the synthesis of sex
      hormone-binding globulin (SFIBG), a binding protein that regulates the
      bioavailability of circulating sex steroids to tissues. The present paper reviews
      epidemiological findings relating the risk of cancers of the colo-rectum,
      pancreas, breast, endometrium and prostate to body size (obesity, height) and
      physical activity, and discusses the relationships between obesity and physical
      activity and plasma levels of insulin, IGF-I and IGFBP. Subsequent sections
      review epidemiological findings relating cancer risk to indices of chronic
      hyperinsulinaemia, and to plasma levels of IGF-I and IGFBP. Conclusions are that
      chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas and
      endometrium, and also possibly of the breast. On the other hand, elevated plasma
      IGF-I, as total concentrations or relative to levels of IGFBP-3, appears to be
      related to an increased risk of prostate cancer, breast cancer in young women,
      and possibly cob-rectal cancer. For cancers of the endometrium, breast and
      prostate, these findings are discussed in the context of relationships between
      insulin and IGF-I and levels of bioavailable sex steroids.

PMID- 11310430
TI  - "Donor" muscle structure and function after end-to-side neurorrhaphy.
AB  - End-to-end nerve coaptation is the preferred surgical technique for peripheral
      nerve reconstruction after injury or tumor extirpation. However, if the proximal
      nerve stump is not available for primary repair, then end-to-side neurorrhaphy
      may be a reasonable alternative. Numerous studies have demonstrated the
      effectiveness of this technique for muscle reinnervation. However, very little
      information is available regarding the potential adverse sequelae of end-to-side
      neurorrhaphy on the innervation and function of muscles innervated by the "donor"
      nerve. End-to-side neurorrhaphy is hypothesized to (1) acutely produce partial
      donor muscle denervation and (2) chronically produce no structural or functional
      deficits in muscles innervated by the donor nerve. Adult Lewis rats were
      allocated to one of two studies to determine the acute (2 weeks) and chronic (6
      months) effects of end-to-side neurorrhaphy on donor muscle structure and
      function. In the acute study, animals underwent either sham exposure of the
      peroneal nerve (n = 13) or end-to-side neurorrhaphy between the end of the tibial
      nerve and the side of the peroneal nerve (n = 7). After a 2-week recovery period,
      isometric force (F(0) was measured, and specific force (sF(0) was calculated for
      the extensor digitorum longus muscle ("donor" muscle) for each animal.
      Immunohistochemical staining for neural cell adhesion molecule (NCAM) was
      performed to identify populations of denervated muscle fibers. In the chronic
      study, animals underwent either end-to-side neurorrhaphy between the end of the
      peroneal nerve and the side of the tibial nerve (n = 6) or sham exposure of the
      tibial nerve with performance of a peroneal nerve end-to-end nerve coaptation
      approximately 6), to match the period of anterior compartment muscle denervation
      in the end-to-side neurorrhaphy group. After a 6-month recovery period,
      contractile properties of the medial gastrocnemius muscle ("donor" muscle) were
      measured. Acutely, a fivefold increase in the percentage of denervated muscle
      fibers (1 +/0 0.7 percent to 5.4 +/-2.7 percent) was identified in the donor
      muscles of the animals with end-to-side neurorrhaphy (p < 0.001). However, no
      skeletal muscle force deficits were identified in these donor muscles.
      Chronically, the contractile properties of the medial gastrocnemius muscles were
      identical in the sham and end-to-side neurorrhaphy groups. These data support our
      two hypotheses that end-to-side neurorrhaphy causes acute donor muscle
      denervation, suggesting that there is physical disruption of axons at the time of
      nerve coaptation. However, end-to-side neurorrhaphy does not affect the long-term
      structure or function of muscles innervated by the donor nerve.

PMID- 11310431
TI  - Advanced distal colonic lesions as predictors of advanced lesions in the proximal
      colon.

PMID- 11310432
TI  - A prospective randomised multicentre trial comparing 10F Teflon Tannenbaum stents
      with 10F polyethylene Cotton-Leung stents in patients with malignant common duct
      strictures.

PMID- 11310433
TI  - EDHF -- are there gaps in the pathway?

PMID- 11310434
TI  - Location of the initiation site of calcium transients and sparks in rabbit heart
      Purkinje cells.
AB  - 1. The distribution and localization of Ca2+ transients and Ca2+ sparks in
      isolated adult rabbit Purkinje cells were examined using confocal microscopy and
      the Ca2+ indicator fluo-3. 2. When cells were field stimulated in 2.0 mM Ca2+
      buffer, a transverse confocal line scan (500 Hz) showed that the fluorescence
      intensity was greatest at the cell periphery during the onset of the Ca2+
      transient ([Ca2+]i). In contrast, the [Ca2+]i of ventricular cells showed a more
      uniform pattern of activation across the cell. Staining with di-8-ANEPPS revealed
      that Purkinje cells lack t-tubules, whereas ventricular cells have an extensive t
      tubular system. 3. When we superfused both cell types with a buffer containing 5
      mM Ca2+-1 microM isoproterenol (isoprenaline) they produced Ca2+ sparks
      spontaneously. Ca2+ sparks occurred only at the periphery of Purkinje cells but
      occurred throughout ventricular cells. Sparks in both cell types could be
      completely abolished by addition of the SR inhibitor thapsigargin (500 nM). Brief
      exposure to nifedipine (10 microM) did not reduce the number of spontaneous
      sparks. 4. Immunofluorescence staining of Purkinje cells with anti-ryanodine
      antibody revealed that ryanodine receptors (RyRs) are present at both peripheral
      and central locations. 5.Computer simulations of experiments in which the calcium
      transient was evoked by voltage clamp depolarizations suggested that the increase
      in calcium observed in the centre of the cell could be explained by simple
      buffered diffusion of calcium. These computations suggested that the RyRs deep
      within the cell do not contribute significantly to the calcium transient. 6.
      These results provide the first detailed, spatially resolved data describing Ca2+
      transients and Ca2+ sparks in rabbit cardiac Purkinje cells. Both types of events
      are initiated only at subsarcolemmal SR Ca2+ release sites suggesting that in
      Purkinje cells, Ca2+ sparks only originate where the sarcolemma and sarcoplasmic
      reticulum form junctions. The role of the centrally located RyRs remains unclear.
      It is possible that because of the lack of t-tubules these RyRs do not experience
      a sufficiently large Ca2+ trigger during excitation-contraction (E-C) coupling to
      become active.

PMID- 11310435
TI  - Psychiatric features of vCJD similar in France and UK.

PMID- 11310436
TI  - Authorship, inclusion and hierarchy.

PMID- 11310437
TI  - Alcohol and the vanishing paradox: comments on Gmel et al.

PMID- 11310438
TI  - Where should alcohol problems prevention be targeted? Comments on Gmel et al.

PMID- 11310439
TI  - Cannabis as a gateway drug: comments on Fergusson & Horwood (2000).

PMID- 11310440
TI  - A dialogue with the alcohol industry: prohibition or harm reduction.

PMID- 11310441
TI  - Diphenhydramine dependence.

PMID- 11310442
TI  - Zentralblatt fur Bakteriologie--100 years ago: agglutination and filament
      formation of Proteus bacteria and maternal-fetal transfer of agglutinins.

PMID- 11310443
TI  - Virulence factors of Helicobacter pylori.
AB  - To date a number of virulence factors have been identified and characterised from
      the gastric pathogen Helicobacter pylori. The vacuolating toxin (VacA) is a major
      determinant of H. pylori-associated gastric disease. In non-polarised cells, VacA
      alters the endocytic pathway, resulting in the release of acid hydrolases and the
      reduction of both extracellular ligand degradation and antigen processing. The
      toxin forms trans-membrane anion-specific channels and reduces the
      transepithelial electrical resistance of polarized monolayers. Localization of
      the VacA channels in acidic intracellular compartments causes osmotic swelling
      which, together with membrane fusion, leads to vacuole formation. The neutrophil
      activating protein of H. pylori (HP-NAP) induces the production of oxygen
      radicals in human neutrophils via a cascade of intracellular activation events
      which may contribute to the damage of the stomach mucosa. This protein has
      recently been shown to be an important antigen in the human immune response to H.
      pylori infection. In addition, mice vaccinated with recombinant HP-NAP were
      protected against H. pylori challenge. H. pylori strains that are associated with
      severe tissue damage and inflammation possess the cag pathogenicity island that
      contains several genes encoding factors involved in the induction of
      proinflammatory cytokines/chemokines and of a type IV secretion system involved
      in the delivery of a highly immunogenic protein, CagA, into eukaryotic cells.
      Recent advances in our understanding of the involvement of VacA, HP-NAP and the
      CagA/Type IV secretion system in the H. pylori-associated disease process are
      discussed in this review.

PMID- 11310444
TI  - Suppression of type 2 NO-synthase activity in macrophages by Candida albicans.
AB  - Macrophages (Mphi) are important for the defence against experimental
      disseminated candidiasis. Nitric oxide (NO) generated by the inducible isoform of
      NO-synthase (iNOS or NOS2) is thought to contribute to candidacidal effector
      functions by activated Mphi. In vitro, however, Mphi cannot control the growth
      and hyphal formation of Candida (C.) albicans. Using mouse peritoneal exudate
      Mphi stimulated with IFN-gamma and LPS, we examined the effect of C. albicans on
      NO synthesis, NOS2 enzyme activity and macrophage survival. C. albicans
      effectively inhibited the production of NO via suppression of total NOS2 protein
      and enzyme activity. Hyphal formation of C. albicans and direct interaction with
      host cells was required for maximum inhibition of NO production, whereas non
      filamentous C. albicans mutants released soluble products that effected only
      partial inhibition. Ultimately, Mphi underwent apoptotic cell death after
      infection with C. albicans wild-type strains capable of hyphal formation,
      indicated by loss of the mitochondrial membrane potential and onset of chromatin
      degradation. NO suppression and Mphi killing are potent activities of C. albicans
      that may augment virulence of C. albicans.

PMID- 11310445
TI  - Instability and site-specific excision of integration-proficient
      mycobacteriophage L5 plasmids: development of stably maintained integrative
      vectors.
AB  - Integrative vectors expressing foreign genes are used as tools for the
      development of recombinant vaccines in mycobacteria since it is assumed that
      these vectors are stably maintained even without antibiotic selection. We here
      demonstrate that integration-proficient vectors are lost from the mycobacterial
      genome in high frequency. Loss of integrated vectors occurred in recA+ and in
      recA-strains, indicating a RecA-independent mechanism. Loss of the integrated
      vector was prevented when integrase gene function was carried on a separate
      plasmid that is unable to replicate in mycobacteria, indicating that excision is
      a function of integrase. By providing attP in cis and integrase function in
      trans, vectors integrating at the attB site are stably maintained, even when
      carrying genes that deleteriously affect the host.

PMID- 11310446
TI  - Characteristics of a new epidemic MRSA in Germany ancestral to United Kingdom
      EMRSA 15.
AB  - In 1996 a new epidemic MRSA emerged in three hospitals North of Berlin. This
      strain, Barnim epidemic MRSA, was isolated in 15 hospitals in Northern Germany in
      1997 and 29 hospitals throughout Germany in 1998. Isolates of this clone are non
      typeable by phages, its resistance phenotype is PEN, OXA, ERY, CLI, CIP
      (genotype: mecA, ermC, mutations in grlA and gyrA). The Sma I macrorestriction
      pattern corresponds to particular phage group II strains which is confirmed by
      the 16S-23S rRNA gene spacer pattern. Isolates of this clone differ by less than
      three Sma I macrorestriction fragments from isolates of the EMRSA15 clone from
      the United Kingdom, the most common epidemic MRSA isolates in the United Kingdom
      in recent years. Both epidemic strains produce enterotoxin C and possess the sec
      determinant for this toxin, the configuration of the mec regulon is mecI-,
      mecRB+, mecRC+. Both share the same Alu I pattern of PCR amplimers of the 3' end
      region of the coagulase gene. EMRSA 15 and Barnim EMRSA share a common multilocus
      sequence type indicating a recent, shared evolutionary origin.

PMID- 11310447
TI  - Intimin from Shiga toxin-producing Escherichia coli and its isolated C-terminal
      domain exhibit different binding properties for Tir and a eukaryotic surface
      receptor.
AB  - The outer membrane protein intimin plays a crucial role in the attaching and
      effacing process employed by different enteropathogens to colonize the epithelial
      surface of their hosts. In this study we have characterized the C-terminal
      binding domain of intimin from the Shiga toxin-producing Escherichia coli strain
      413/89-1, that belongs to the beta-subtype of intimins. We found that a fusion of
      this domain to the maltose-binding protein binds efficiently to both the
      translocated intimin receptor (Tir) and the surface of uninfected eukaryotic host
      cells. In contrast, no such binding was observed with the full-length protein
      localized on the bacterial surface. As the C-terminal domain of intimin and the
      full-length protein differ in their binding activity, we suggest that the intimin
      binding domain might be controlled by the N-terminal portion of the molecule to
      prevent unproductive interactions with molecules in the lumen of the gut.

PMID- 11310448
TI  - Characterization of the type III secretion locus of Bordetella pertussis.
AB  - Multiple sequence comparisons of proteins of the LcrD/FlbF family allowed the
      design of primers that specifically amplify sequences coding for type III
      secretion components. Amplification of Bordetella pertussis DNA with these
      primers yielded a fragment that was further used as a probe for screening a
      genomic library. The nucleotide sequence of a positive clone revealed a 2100-bp
      gene, called bcrD, which specifies a 75-kDa polypeptide homologous to the
      Yersinia LcrD protein. Chromosome walking allowed the characterization of a 35-kb
      DNA segment that contains the entire locus and flanking housekeeping genes. The
      B. pertussis type III secretion locus consists of more than 30 open reading
      frames (ORFs), most of which are identical to annotated genes of Bordetella spp
      and share similarities with known type III secretion genes of related bacteria.
      In order to assess the function of this locus, we engineered a bcrD null mutant.
      However, none of the tested phenotypes, such as protein secretion, cellular
      invasion, cytotoxicity or mouse lung colonization, differentiated the mutant from
      its parental strain. Studies of bcrD and bscN expressions indicated that, under
      our experimental conditions, these genes are not expressed in vitro. Restriction
      analyses on pulsed-field gel electrophoresis allowed the type III locus mapping
      at coordinate position 1,590 kb on the Tohama I strain chromosome.

PMID- 11310449
TI  - Virulence in the chick model and stress tolerance of Salmonella enterica serovar
      Orion var. 15+.
AB  - Three Salmonella enterica serovar Orion var. 15+ isolates of distinct provenance
      were tested for survival in various stress assays. All were less able to survive
      desiccation than a virulent S. Enteritidis strain, with levels of survival
      similar to a rpoS mutant of the S. Enteritidis strain, whereas one isolate
      (F3720) was significantly more acid tolerant. The S. Orion var. 15+ isolates were
      motile by flagellae and elaborated type-1 and curli-like fimbriae; surface
      organelles that are considered virulence determinants in Salmonella pathogenesis.
      Each adhered and invaded HEp-2 tissue culture cells with similar proficiency to
      the S. Enteritidis control but were significantly less virulent than S.
      Enteritidis in the one-day-old and seven-day-old chick model. Given an oral dose
      of 1 x 10(3) cfu to one-day-old chicken, S. Orion var. 15+ isolates colonised 25%
      of liver and spleens examined at 24 h whereas S. Enteritidis colonised 100% of
      organs by the same with the same dose. Given an oral dose of 1 x 10(7) cfu at
      seven-day old, S. Orion var. 15+ failed to colonise livers and spleens in any
      bird examined at 24 h whereas S. Enteritidis colonised 50% of organs by the same
      with the same dose. Based on the number of internal organs colonised, one of the
      three S. Orion var. 15+ isolates tested (strain F3720) was significantly more
      invasive than the other two (B1 and B7). Also, strain F3720 was shed less than
      either B1 or B7 supporting the concept that there may be an inverse relationship
      between the ability to colonise deep tissues and to persist in the gut. These
      data are discussed in the light that S. Orion var. 15+ is associated with
      sporadic outbreaks of human infection rather than epidemics.

PMID- 11310450
TI  - Non-Hodgkin's lymphoma after primary Hodgkin's disease in the German Hodgkin's
      Lymphoma Study Group: incidence, treatment, and prognosis.
AB  - PURPOSE: The cumulative incidence for non-Hodgkin lymphoma's (NHL) after primary
      Hodgkin's disease (HD) ranges between 1% and 6%. To investigate the course of
      disease for secondary NHL, we retrospectively analyzed patients treated within
      clinical trials of the German Hodgkin's Lymphoma Study Group (GHSG) since 1981.
      PATIENTS AND METHODS: From 1981 to 1998, the GHSG conducted three generations of
      clinical trials for the treatment of primary HD involving a total of 5,406
      patients. Reference histology by an expert panel was obtained for 4,104 of the
      patients. Data on incidence, treatment, and outcome of secondary NHL were updated
      in March 1999. RESULTS: At first diagnosis of HD, the pathologists rejected 114
      (2.1%) of 5,520 cases initially diagnosed as HD and rediagnosed them as primary
      NHL. Fifty-two (0.9%) of the remaining 5,406 patients developed a secondary NHL.
      One patient was excluded from further analyses because of insufficient
      documentation. Six patients had no further therapy because of patient refusal (n
      = 1) or rapidly progressive disease (n = 5). For the remaining 45 patients,
      overall response rate was 43% (36% complete response and 7% partial response).
      The actuarial 2-year freedom from treatment failure (FFTF) and overall survival
      (OS) for all patients was 24% and 30%, respectively, and for patients with
      diffuse large-cell lymphoma, it was 28% and 35%, respectively. Time of occurrence
      of secondary NHL after first diagnosis of HD and variables employed in the age
      adjusted International Prognostic Factor Index (IPFI) significantly influenced
      treatment outcome. CONCLUSION: In the GHSG, the incidence of secondary NHL with
      0.9% is relatively low compared with previously reported series. The prognosis of
      secondary NHL seems dismal and is significantly influenced by time of occurrence
      and the age-adjusted IPFI. In a subset of patients with secondary NHL, long-term
      disease-free survival could be achieved.

PMID- 11310451
TI  - Physiologic aspects of natural and surgical menopause.
AB  - With oophorectomy, the physiologic changes associated with menopause occur
      quickly and with a significant impact on a woman's quality of life. In naturally
      menopausal women, ovarian hormone biosynthesis provides low circulating levels of
      estrogen and androgen. In the surgically menopausal woman, estrogen and androgen
      levels are significantly reduced. In surgically menopausal women for whom
      supplemental estrogen is prescribed, sex hormone binding globulin levels increase
      dramatically, resulting in reduced bioavailability of the remaining estrogens and
      androgens that result from peripheral conversion. This paper reviews the
      physiologic changes associated with natural and surgical menopause and the
      effects of estrogens and androgens at the cellular level. It describes the
      effects of hormone replacement on endogenous hormones and on the symptoms of
      menopause that result from physiologic changes, including vasomotor instability,
      sexual dysfunction and urinary complications. It also addresses the effects of
      estrogen/androgen therapy on physiologic symptoms.

PMID- 11310452
TI  - Open letter from ACRM to HCFA on proposed Medicare PPS. American Congress of
      Rehabilitation Medicine. Health Care Financing Administration.

PMID- 11310453
TI  - The NHS plan--the sound of cavalry or zebras?

PMID- 11310454
TI  - Is a chest pain observation unit likely to be cost saving in a British hospital?
AB  - BACKGROUND: Studies from the United States (US) suggest that using a chest pain
      observation unit (CPOU) saves from $567 to $2,030 per case compared with hospital
      admission. These savings will only be reproduced in the United Kingdom (UK) if
      the cost of routine hospital admission is similar. This study aimed to review
      current practice to determine the proportion of patients suitable for CPOU
      evaluation, the cost per case of routine admission and compare this with control
      groups in US studies. METHODS: 300 patients were randomly selected from those
      admitted with chest pain between January and June 1998. Two independent observers
      reviewed the case notes to determine who would have been suitable for CPOU
      management. Resource use of those selected was then determined. RESULTS: Notes
      were retrieved for 285 patients. A total of 106 (37.2%) were suitable for CPOU
      care. Mean length of stay was 51 hours (median 24). Only two patients were
      admitted to the coronary care unit. Interventional cardiology was limited to two
      angiograms, one angioplasty and one bypass graft. Estimated mean cost per patient
      was 458 pounds ($733) with interventional cardiology included, 356 pounds ($570)
      without. CONCLUSION: Potential exists for the introduction of CPOU care to reduce
      health service costs in the UK. However, the magnitude of cost savings
      demonstrated in US studies were achieved by comparison to relatively high
      inpatient costs and should not be extrapolated. Economic evaluation of the CPOU
      should be repeated in the UK. The inclusion of interventional cardiology costs is
      an important determinant of cost effectiveness.

PMID- 11310455
TI  - Biochemical markers in the management of suspected acute myocardial infarction in
      the emergency department.
AB  - OBJECTIVES: To compare cardiac troponin T, myoglobin, CK, CKMB activity, CKMB
      mass and the initial electrocardiogram in the early diagnosis of myocardial
      infarction in the emergency department. Methods-Biochemical markers were measured
      at presentation in patients with a possible diagnosis of acute myocardial
      infarction. Based on the clinical notes, patients were grouped as "definite
      myocardial infarction" (n = 50), "definite no myocardial infarction" (n = 81) and
      "uncertain" (n = 96). Sensitivity and specificity and positive and negative
      predictive values were calculated using the 131 patients with definitely present
      or absent myocardial infarction. RESULTS: The initial electrocardiogram was more
      sensitive than any of the markers in the first six hours from symptom onset
      sensitivity 74% (95%CI 61% to 88%). The positive predictive value of the initial
      electrocardiogram was 97% in the first six hours; the markers ranged from 47% to
      67%. The negative predictive value of the initial electrocardiogram was 85% in
      the first six hours; the markers ranged from 61% to 70%. Four patients with non
      diagnostic electrocardiograms presenting beyond six hours after pain onset had a
      myocardial infarct detected by at least three of the biochemical markers in each
      case. CONCLUSIONS: The electrocardiogram is of more diagnostic use than
      biochemical markers in the first six hours after the onset of pain, but
      biochemical markers give additional positive diagnostic information in patients
      presenting later than this. The negative predictive accuracy of biochemical
      markers is too low for a single sample to be useful for excluding myocardial
      infarction in the first six hours after onset of symptoms.

PMID- 11310456
TI  - Prehospital rapid sequence induction by emergency physicians: is it safe?
AB  - OBJECTIVES: To determine if there were differences in practice or intubation
      mishap rate between anaesthetists and accident and emergency physicians
      performing rapid sequence induction of anaesthesia (RSI) in the prehospital
      setting. METHODS: All patients who underwent RSI by a Helicopter Emergency
      Medical Service (HEMS) doctor from 1 May 1997 to 30 April 1999 were studied by
      retrospective analysis of in-flight run sheets. Intubation mishaps were
      classified as repeat attempts at intubation, repeat drug administration and
      failed intubation. RESULTS: RSI was performed on 359 patients by 10 anaesthetists
      (202 patients) and nine emergency physicians (157 patients). Emergency physicians
      recorded a larger number of patients as having Cormack and Lehane grade 3 or 4
      laryngoscopy than anaesthetists (p<0.0001) but were less likely to use a gum
      elastic bougie to assist intubation (p=0.024). Patients treated by emergency
      physicians did not have a significantly different pulse, blood pressure, oxygen
      saturation or end tidal CO2 to patients treated by anaesthetists at any time
      after intubation. Emergency physicians were more likely to anaesthetise patients
      with a Glasgow Coma Score >12 than anaesthetists (p=0.003). There were two failed
      intubations (1%) in the anaesthetist group and four (2.5%) in the emergency
      physician group. Repeat attempts at intubation and repeat drug administration
      occurred in <2% of each group. CONCLUSIONS: RSI performed by emergency physicians
      was not associated with a significantly higher failure rate or an increased
      number of intubation mishaps than RSI performed by anaesthetists. Emergency
      physicians were able to safely administer sedative and neuromuscular blocking
      drugs in the prehospital situation. It is suggested that emergency physicians can
      safely perform rapid sequence induction of anaesthesia and intubation.

PMID- 11310458
TI  - What future for chest pain observation units?

PMID- 11310457
TI  - Magnetic resonance imaging as the primary imaging modality in children presenting
      with acute non-traumatic hip pain.
AB  - The role of magnetic resonance imaging (MRI) in children presenting with acute
      non-traumatic hip pain was evaluated prospectively. Hip MRI was performed in
      addition to standard investigations (arthrosonography +/- hip radiographs) in 50
      children presenting to the accident and emergency department of a paediatric
      hospital. MRI was performed on an open 0.23T system and comprised gradient echo
      T1 weighted coronal, fast spin echo T2 weighted coronal and inversion recovery
      spin echo (IRSE) axial sequences. Diagnostic quality MRI examinations were
      obtained in 94% of children. The IRSE sequence was the most reliable at
      determining underlying disorder (p<0.002). Interobserver agreement on the MRI
      examinations was very good with unweighted kappa value of 0.89, 95% confidence
      intervals 0.79, 0.99. Sensitivity of MRI was 0.79 (0.68, 0.90, specificity 1.00
      (0.89, 1.00), accuracy 0.81 (0.70, 0.92), PPV 1.00 (0.89, 1), NPV 0.36 (0.25,
      0.47). Sensitivity of standard imaging was 0.70 (0.54-0.86), specificity 0.57
      (0.41, 0.73), accuracy 0.72 (0.56, 0.88), PPV 0.91 (0.75, 1.00), NPV 0.24 (0.08,
      0.40). MRI correctly identified all seven children with serious underlying
      disorder whereas conventional imaging correctly diagnosed only two. Pelvic
      musculoskeletal infection was associated with the combination of marked
      alteration in signal in tissues adjacent to a symptomatic hip and an erythrocyte
      sedimentation rate of >20 mm 1st h (p<0.0001). In conclusion, MRI is a practical,
      well accepted and accurate non-invasive imaging technique in children presenting
      with acute non-traumatic hip pain. Combined with inflammatory markers MRI can be
      used to determine those children who require aggressive management. Where it is
      available, MRI is the imaging modality of choice in this condition.

PMID- 11310459
TI  - Sedation for children requiring wound repair: a randomised controlled double
      blind comparison of oral midazolam and oral ketamine.
AB  - OBJECTIVE: To compare the efficacy of oral ketamine (10 mg/kg) with oral
      midazolam (0.7 mg/kg) in providing sedation for suturing of lacerations. METHOD:
      Prospective, randomised, double blinded trial with consecutive, concealed
      recruitment of 59 children aged 1 to 7 with wounds requiring local anaesthetic
      (LA) injection or topical LA with an anxiety score greater than one. RESULTS:
      Tolerance to LA injection was better with ketamine (p=0.029) and tolerance to
      procedure after LA injection showed a trend towards being improved with ketamine
      (p=0.067). There was no difference in tolerance to LA application or procedure in
      children receiving topical LA. Time to reach a sedation score of less than four
      was faster with ketamine (medians 20 versus 43 minutes, p=0.001) but times from
      dosing to discharge (medians 105 and 110 minutes) were similar. Inconsolable
      agitation was reported with midazolam in six cases. Dysphoria was not noted with
      ketamine. Vomiting was more common with ketamine but not significantly so (six
      versus two, p = 0.14). Oxygen desaturations were noted in both groups. Ataxia
      after discharge was seen in four patients, two in each group. Thirty six per cent
      of children showed new behavioural disturbances in the two weeks after discharge,
      more commonly in the midazolam group (p=0.048). CONCLUSIONS: At these doses
      tolerance to LA injection was better in children receiving ketamine, with fewer
      behavioural changes noted in the first two weeks. Midazolam at this dose caused
      dysphoric reactions, which may have affected the results. Continuous pulse
      oximetry monitoring is required when using these drugs. Vomiting and prolonged
      ataxia occurred in a few patients.

PMID- 11310460
TI  - A comparison of intramuscular ketamine with high dose intramuscular midazolam
      with and without intranasal flumazenil in children before suturing.
AB  - OBJECTIVES: (a) To compare the use of high dose intramuscular midazolam with and
      without intranasal flumazenil in children after suturing. (b) To compare the use
      of high dose intramuscular midazolam with low dose intramuscular ketamine in
      children before suturing. METHODS: 87 children, aged between 1 and 7 years,
      presenting with simple wounds needing sedation, were studied. Children considered
      combative (n=47) were given ketamine (2.5 mg/kg intramuscularly). The remaining
      40 children were given midazolam (0.4 mg/kg intramuscularly) with and without
      flumazenil (25 microg/kg, intranasally). RESULTS: The median oxygen saturation
      was 97% in both midazolam groups. Flumazenil significantly reduced the amount of
      agitation during recovery (p=0.048) and also the time at which children were
      ready for discharge (median 55 versus 95 minutes, p value <0.001). After
      discharge both midazolam groups had an unsteady gait (75%) and there was no
      significant difference in the duration. As expected because of the deliberate
      selection of combative children into the ketamine group, the pre-sedation
      behaviour was slightly more disturbed compared with the midazolam group (p=0.10).
      However, the ketamine group was less agitated during local anaesthetic and
      suturing p<0.001. CONCLUSION: Intramuscular midazolam (0.4 mg/kg) did not
      effectively sedate the children, in that a significant number still had to be
      restrained. However, none could remember the suturing. Intranasal flumazenil
      seems to be effective in shortening the time to discharge. If midazolam is to be
      used then a dose high enough to produce full amnesia should be used, there seems
      to be no advantage in increasing the dose further. Low dose intramuscular
      ketamine remains the drug of choice.

PMID- 11310461
TI  - Intravenous ketamine plus midazolam is superior to intranasal midazolam for
      emergency paediatric procedural sedation.
AB  - OBJECTIVES: This study compared intranasal midazolam (INM) with a combination of
      intravenous ketamine and intravenous midazolam (IVKM) for sedation of children
      requiring minor procedures in the emergency department. METHOD: A single blinded
      randomised clinical trial was conducted in the emergency department of a major
      urban paediatric hospital. Subjects requiring sedation for minor procedures were
      randomised to receive either INM (0.4 mg/kg) or intravenous ketamine (1 mg/kg)
      plus intravenous midazolam (0.1 mg/kg). Physiological variables and two
      independent measures of sedation (Sedation Score and Visual Analogue Sedation
      Scale) were recorded before sedation and at regular intervals during the
      procedure and recovery period. Times to adequate level of sedation and to
      discharge were compared. RESULTS: Fifty three patients were enrolled over a 10
      month period. Sedation was sufficient to complete the procedures in all children
      receiving IVKM and in 24 of the 26 receiving INM. Onset of sedation was an
      average of 5.3 minutes quicker with IVKM than with INM (95%CI 3.2, 7.4 minutes,
      p<0.001). Children given INM were discharged an average of 19 minutes earlier
      than those given IVKM (95%CI 4, 33 minutes, p=0.02). Mean Sedation Scores and
      Visual Analogue Sedation Scale scores for the 30 minutes after drug
      administration were significantly better in children given IVKM compared with INM
      (2.4 and 1.8 versus 3.5 and 3.8, respectively). Both doctors and parents were
      more satisfied with sedation by intravenous ketamine and midazolam. CONCLUSIONS:
      Intravenous ketamine plus midazolam used in an appropriate setting by experienced
      personnel provides an excellent means of achieving sedation suitable for most non
      painful minor procedures for children in the emergency department. This
      combination is superior to INM in terms of speed of onset and consistency of
      effect. INM delivered via aerosol spray has a more variable effect but may still
      be adequate for the completion of many of these procedures.

PMID- 11310462
TI  - A randomised controlled trial to determine the effectiveness of double Tubigrip
      in grade 1 and 2 (mild to moderate) ankle sprains.
AB  - OBJECTIVE: To compare functional outcome in patients with acute grade 1 or 2
      (mild to moderate) lateral ankle sprains randomised to treatment with or without
      a double tubigrip bandage (DTG). METHODS: 400 patients presenting to the accident
      and emergency (A&E) departments of a teaching hospital and a district general
      hospital and diagnosed with grade 1 or 2 lateral ankle sprains were randomised to
      treatment with or without a DTG bandage. A standardised telephone questionnaire
      was performed one week after presentation. The main outcome measures were: number
      of days until walking unaided, number of days off work, whether the injury kept
      the patient awake at night, whether analgesia was taken. RESULTS: 197 of 400
      patients completed follow up. There were no significant differences in terms of
      age, sex and occupation between the treatment groups. There were no significant
      differences between those who did and those who did not complete follow up. There
      was no significant difference between the treatment groups for number of days
      until walking unaided (95% CI -0.21 to 0.88 days), number of days off work (95%
      CI -0.70 to 1.02 days) or whether the injury kept the patient awake at night (95%
      CI -10 to 17%). There was a significant difference between the groups in the use
      of analgesia (95% CI 10 to 36%); the difference seemed to be that patients
      treated with DTG required significantly more analgesia. CONCLUSIONS: Treatment of
      grade 1 and 2 ankle sprins with DTG does not seem to lead to a shorter time to
      functional recovery and may increase the requirement for analgesia.

PMID- 11310463
TI  - The use of the spinal board after the pre-hospital phase of trauma management.
AB  - OBJECTIVES: For pre-hospital spinal immobilisation the spinal board is the
      established gold standard. There are concerns that its subsequent use in hospital
      may adversely affect patient outcome. This review examines the effect of
      prolonged patient immobilisation on the spinal board. METHODS: A database search
      of the literature and review of relevant trauma texts. RESULTS: Complications
      associated with the use of the spinal board were found in five clinically
      relevant categories: pressure sore development; inadequacies of spinal
      immobilisation and support; pain and discomfort; respiratory compromise; and
      quality of radiological imaging. CONCLUSION: The spinal board should be removed
      in all patients soon after arrival in accident and emergency departments, ideally
      after the primary survey and resuscitation phases.

PMID- 11310464
TI  - The ATLS course, a survey of 228 ATLS providers.
AB  - Advanced Trauma Life Support (ATLS) courses teach a system for the initial
      assessment and management of trauma patients that aims to optimise initial care
      and reduce mortality and morbidity, and have been adopted worldwide. This
      questionnaire survey characterised those who took up this particular educational
      resource in Scotland during a four year period after its introduction, and
      analysed how they felt it had affected their clinical competence. Irrespective of
      their previous level of training and experience, nearly all surgeons and
      anaesthetists who took this course felt that it had improved their clinical
      skills and other professional attributes. The significance of these results is
      discussed in the context of postgraduate surgical and anaesthetic training in
      Scotland.

PMID- 11310465
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Frusemide or nitrates in acute left ventricular failure.

PMID- 11310466
TI  - Emergency management of cardiac chest pain: a review.
AB  - All patients attending an ED with chest pain that could be cardiac should be
      given a high triage priority to allow rapid assessment and treatment. All
      patients should receive adequate analgesia and aspirin. Patients with AMI who
      require fibrinolytic agents should be identified and treatment started. Other
      high risk patients need inpatient care and may need low molecular weight heparin.
      Low risk patients require rapid, cost effective and efficacious ROMI protocols,
      so they can be discharged safely. CPAUs provide the best way of achieving this.
      Currently the best early protocol seems to be serial CK-MB measurements and
      continuous ST segment monitoring.

PMID- 11310467
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bypass or external rewarming after hypothermic cardiac arrest.

PMID- 11310468
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Using intravenous adenosine in asthmatics.

PMID- 11310469
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. First ECG in chest pain.

PMID- 11310470
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Timing of aspirin administration in acute myocardial infarction.

PMID- 11310471
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. CPAP in acute left ventricular failure.

PMID- 11310472
TI  - Article 5. An introduction to estimation--2: from z to t.
AB  - Provided the sample size is large enough (that is, n greater than 100), the z
      statistic can be used to determine the confidence interval estimation of the
      population mean even when the sigma is not known. In these cases the estimation
      of the standard error of the mean is used. The z statistic is also valid when
      determining the population's proportion based upon a large sample. However, when
      dealing with smaller samples, the z statistic is replaced by the t statistic.
      This makes it possible to estimate, in a population with an unknown standard
      deviation: The probability of getting a sample mean greater than or equal to a
      particular value The value of a sample mean with a particular probability of
      occurring The probability of getting a sample mean between two particular values
      The confidence interval for the estimation of the population mean can also be
      determined using the t statistic.

PMID- 11310473
TI  - The Lazarus phenomenon following recreational drug use.
AB  - A case is reported of the Lazarus phenomenon (the return of spontaneous
      circulation after cardiopulmonary resuscitation had been abandoned) in a patient
      following recreational drug use. The implications for management of cardiac
      arrest in the emergency department are discussed.

PMID- 11310474
TI  - Bedside emergency department ultrasound.

PMID- 11310475
TI  - The millennium celebrations, deliberate self harm. Our experience.

PMID- 11310476
TI  - Death with dignity in the accident and emergency short stay ward.

PMID- 11310477
TI  - Aortic injury review failed to mention the "osseous pinch".

PMID- 11310478
TI  - The tramadol option.
AB  - Tramadol is an option for the treatment of rheumatological pain. Its mode of
      action and safety profile distinguishes it from other opioids. Tramadol differs
      from other opioids by combining a weak opioid and a monoaminergic mode of action.
      It is effective in different types of moderate-to-severe pain, including
      neuropathic pain. Moreover, as the mode of action of tramadol does not overlap
      with that of NSAIDs, it is a useful agent to be combined with these drugs.
      Tramadol induces fewer opioid adverse reactions for a given level of analgesia
      compared with traditional opioids. Common adverse reactions of tramadol such as
      nausea and dizziness, which usually occur only at the beginning of therapy and
      attenuate over time, can be further minimized by up-titrating the drug over
      several days. Dose adjustment is only necessary in patients over 75 years of age,
      or in those with either hepatic or renal insufficiency. Tramadol should be
      avoided or used with caution in epileptics, or in individuals who are receiving
      seizure-threshold lowering drugs. Finally, tramadol has a low risk of abuse
      because it has only a weak opioid effect and its monoaminergic action could
      inhibit the development of dependence. The low abuse potential of tramadol has
      been demonstrated by postmarketing surveillance data.

PMID- 11310479
TI  - Treatment of pain in osteoarthritis.
AB  - Clinical studies have demonstrated that osteoarthritic pain is strongly linked to
      disability and quality of life. Pain relief enables patients to regain their
      mobility and is therefore a key goal in the management of osteoarthritis (OA).
      Osteoarthritis pain is of multifactorial origin, and inflammatory mechanisms play
      only a partial role. Non-opioid analgesics are useful in the control of mild-to
      moderate pain, but have limitations as regards efficacy, and may cause serious
      adverse reactions. Symptomatic slow-acting drugs in OA (SYSADOAs) are
      alternatives, but their usefulness is still unclear. For patients with moderate
      to-severe pain, who do not obtain sufficient pain relief with paracetamol and non
      steroidal anti-inflammatory drugs (NSAIDs) or do not tolerate them, the remaining
      options are opioids. Whereas the adverse reactions of most opioids may preclude
      the use of these drugs in OA patients, tramadol may be suitable. Tramadol has
      been investigated in various studies of OA pain and is indicated as an
      alternative to non-opioids, or as adjunctive therapy when non-opioid therapy is
      insufficient. However, the choice of analgesic treatment in OA must be highly
      individual. No guidelines can rigidly define a treatment regimen for such a
      condition as OA. Simple hints are given how to best use tramadol by selecting the
      right patients and choosing the right dosing strategy.

PMID- 11310480
TI  - The lesson from cancer pain.
AB  - The success of the WHO guidelines for the treatment of cancer pain indicates that
      cancer pain was previously undertreated. At the heart of these guidelines lies
      the three-step analgesic ladder, the last two steps of which consist of
      prescribing opioids. Today, the use of opioids in cancer patients is generally
      accepted, but there are still some concerns over the risks of addiction and
      adverse reactions, and opioids are sometimes withheld from patients who would
      otherwise benefit from them. However, it has been shown that such concerns are
      misplaced: the risks of severe adverse reactions and addiction are low when
      opioids are used correctly in patients with chronic pain. The use of opioids to
      treat benign pain is even less widely accepted in many countries, despite
      recommendations that they should be prescribed. It is emphasized that the use of
      opioids is a valid option for treating benign pain, and they should not be
      withheld from patients who need them. Opioids are always indicated when other
      therapeutic options, including NSAIDs, have failed or are contraindicated. When
      opioids are prescribed, procedures should be followed to provide the patient with
      maximum benefit and minimum risk.

PMID- 11310481
TI  - Current use of analgesics for rheumatological pain.
AB  - Rheumatological pain is the most frequent pain doctors have to deal with. Faced
      with a patient experiencing pain, the clinician must work towards global
      management of the patient, including the prescription of analgesics. The results
      of a European survey amongst 722 general practitioners, rheumatologists,
      orthopaedic surgeons and internal specialists showed that about half of all
      patients treated for moderate-to-severe pain suffered from musculoskeletal pain.
      Despite this high treatment frequency, the management of rheumatological pain was
      generally perceived as problematic by the respondents. The drugs prescribed to
      treat rheumatological pain differed from country to country, but NSAIDs were
      generally the most-prescribed substances. Important reasons given for selecting
      analgesics included efficacy and tolerability, but also tolerance and addiction
      potential. NSAIDs are common first-line drugs, but their adverse reactions and
      interactions have led to paracetamol being recommended more often in this role.
      However, it has been recently demonstrated that the efficacy of paracetamol is
      often inadequate. On the other hand, the reduced risk of GI toxicity of the new
      COX-2 selective inhibitors could assure them a major role in mild-to-moderate
      rheumatological pain treatment. When any of these drugs are no longer effective,
      or when a patient cannot tolerate their adverse reactions, weak opioids should be
      considered. Tramadol is one such drug, which is gaining popularity for the
      treatment of moderate-to-severe rheumatological pain. Finally, strong opioids
      should be used in selected patients when all other options have been exhausted.

PMID- 11310482
TI  - Renal involvement in sarcoidosis.

PMID- 11310483
TI  - Cautions after liver transplantation for familial amyloidotic polyneuropathy.

PMID- 11310484
TI  - Embryonic stem cell.
AB  - Mouse embryonic stem (ES) cells are the cells that possess pluripotential
      differentiation activity into not only all somatic cells but also germ cells.
      Genetic alteration of mouse ES cells can be easily achieved and such genetic
      modification can be introduced into the animal, since ES cells are differentiated
      into germ cells in vivo. This technology enables us to analyze the function of
      any particular genes of interest in mice. And in vitro differentiation induction
      of mouse ES cells into various cell lineages, such as blood cells, neural cells,
      and cardiac muscle cells, has been studied. In vitro hematopoietic
      differentiation experiments were carried out most extensively and can be regarded
      as a model system of induction. Recently, human ES cells have been established.
      Many scientists, clinicians and even mass media have entertained the idea that
      human ES cells can be used after changing the cells into lineage-specific stem
      cells or progenitor cells such as hematopoietic stem cells and neural progenitor
      cells.

PMID- 11310485
TI  - Elevated level of soluble HLA class I antigens in serum and bronchoalveolar
      lavage fluid in patients with sarcoidosis.
AB  - OBJECTIVE: Soluble HLA class I antigens (sHLAs) in human serum have been reported
      to be associated with allografts and autoimmune disease and could modify
      immunological reactions induced by membrane type HLAs. To investigate the
      clinical significance of sHLAs in sarcoidosis, we assessed concentrations of
      sHLAs in both serum and bronchoalveolar lavage fluid (BALF) and also examined
      their production by peripheral blood mononuclear cells (PBMCs) and BALF cells.
      METHODS: Concentrations of sHLAs were determined by  enzyme-linked immunosorbent
      assay, using a monoclonal  antibody against HLA class I (W6/32) and an enzyme
      labeled polyclonal antibody to human beta2-microglobulin. PBMCs and BALF cells
      were cultured in the presence or absence of either LPS or PHA. PATIENTS: Serum
      levels of sHLAs were assessed in 96 patients with sarcoidosis and in 32 healthy
      control subjects. sHLAs concentrations in BALF were also investigated in 17
      active sarcoidosis patients and in 13 control subjects. RESULTS: sHLAs levels in
      both serum and BALF were higher in sarcoidosis cases than in control subjects
      (p<0.05, in both). In the patients, values were significantly higher in active
      than in inactive stages (p<0.001) and significantly correlated with angiotensin
      converting enzyme (ACE) levels. Both PBMCs and BALF cells produced enhanced
      amounts of sHLAs in patients with active sarcoidosis compared with those in
      control subjects. CONCLUSION: These results demonstrated that the level of sHLAs
      in serum is a useful index of disease activity of sarcoidosis, partly reflecting
      production by PBMCs and BALF cells.

PMID- 11310486
TI  - An association between an antibody against Chlamydia pneumoniae and common
      carotid atherosclerosis.
AB  - OBJECTIVE: Chlamydia pneumoniae (C. pneumoniae) is an important pathogen for
      infections of the respiratory tract, and there are recently also a number of
      reports suggesting its relation with atherosclerosis. This study was performed to
      clarify the relation between C. pneumoniae infection and sclerotic lesions of the
      common carotid arteries. METHODS AND PATIENTS: We evaluated sclerotic lesions of
      common carotid arteries by ultrasonography in 147 in-patients (mean age, 70
      years; 95% confidence interval, 68-72) in the internal medicine ward, and studied
      the relation of the known risk factors for atherosclerosis including C.
      pneumoniae infection. An ultrasonograph and 7.5 MHz linear type B-mode probe were
      used by a specialist to evaluate sclerotic lesions of common carotid arteries. C.
      pneumoniae infection was determined by measuring anti-C. pneumoniae IgG specific
      antibody level (IgG index) using enzyme-linked immunosorbent assay (ELISA) method
      with serum of fasting blood, which had been preserved at -70 degrees C. RESULTS:
      IgG index (p=0.0263), from multiple regression analysis using various risk
      factors as explanatory variables, was a significant independent contributing
      factor (R2=0.3465, p<0.0001) along with known risk factors such as male
      (p=0.0289), age (p=0.0007), Brinkman index (p=0.0067), hypertension (p=0.0443)
      and T-Chol (p=0.0220). CONCLUSION: This study confirmed that the observations of
      an association between antibody against C. pneumoniae and common carotid
      atherosclerosis in Western nations is also present in Japan. Our results suggests
      that C. pneumoniae infection is also an important risk factor for common carotid
      atherosclerosis.

PMID- 11310487
TI  - Significant reduction of methicillin-resistant Staphylococcus aureus bacteremia
      in geriatric wards after introduction of infection control measures against
      nosocomial infections.
AB  - OBJECTIVES: (1) To investigate the efficacy of infection control measures against
      methicillin-resistant Staphylococcus aureus (MRSA) bacteremias in geriatric
      wards. (2) To identify predisposing risk factors for MRSA bacteremia. METHODS:
      Cases with nosocomial bacteremias were retrospectively analyzed between January
      1991 and March 1995. The study period was divided into four annual periods and
      the period 1, January to December 1991, was applied as the control. MATERIALS: We
      investigated patients with nosocomial bacteremias in geriatric wards (190 beds)
      of AINO Memorial Hospital, affiliated with Nagasaki University. RESULTS: A
      significant reduction in cases with MRSA-induced nosocomial bacteremia was
      observed after the introduction of a stringent infection control and prevention
      program (period 1 vs. periods 2, 3, and 4: p<0.00833, p<0.00167, and p<0.00167,
      respectively). The major source of bacteremia included urinary tract infections,
      intravenous catheter-related infections, and infected decubitus ulcers.
      Improvement of decubitus ulcer was associated with a significant reduction in
      MRSA bacteremia (period 1 vs. periods 2 and 3: p<0.00017 and p<0.00833).
      CONCLUSION: Stringent infection control programs, including prevention and
      treatment of decubitus ulcers, are necessary in geriatric wards to reduce and
      prevent MRSA bacteremia.

PMID- 11310488
TI  - Complications during clinical courses of Pneumocystis carinii pneumonia in
      patients with acquired immunodeficiency syndrome.
AB  - OBJECTIVE: To describe the incidence of complications before and during therapy
      of Pneumocystis carinii pneumonia (PCP) in patients with acquired
      immunodeficiency syndrome (AIDS). METHODS: A retrospective review of the
      patient's medical records. PATIENTS: A total of 29 patients with AIDS and PCP who
      were admitted to the AIDS Clinical Center, International Medical Center of Japan
      from July 1996 to November 1999. RESULTS: Adverse effects were found in 24
      (88.9%) of 27 patients treated with trimethoprim/sulfamethoxazole (T/S), 6
      (46.1%) of 13 treated with parenteral pentamidine, and 2 (20%) of 10 treated with
      inhaled pentamidine. Infectious and/or non-infectious complications were found in
      25 (86.2%) of 29 study patients. Regarding infectious complications, 16 (55.2%)
      were found on admission and 10 cases (34.5%) with infectious complications were
      identified during admission; including oral candidiasis (37.9% and 17.2%,
      respectively) and genital herpes (3.4% and 6.9%, respectively). Cytomegalovirus
      antigenemia was detected in 4 cases (13.8%) on admission and 12 cases (41.4%)
      during admission. Non-infectious complications affected 11 cases (37.9%) on
      admission, and 6 cases (20.7%) during admission, the latter included heart
      failure (10.3%) and pneumothorax (6.9%). PCP was successfully treated in all but
      one patient who suffered from repeated pneumothorax. CONCLUSION: Treatment of PCP
      can be problematic and it is important to be aware of the high incidence of
      various complications that can occur during the treatment of PCP.

PMID- 11310489
TI  - Hypervascular liver metastasis from hypovascular ductal cell carcinoma of the
      pancreas.
AB  - In a case of hypervascular metastatic liver tumor, the vascularity of primary
      focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we
      thought before the operation that the two lesions were double cancers.
      Histological examination showed that the stromal volume of metastatic tumorous
      tissue was richer than that of the primary focus. It was suggested that the
      difference in the stromal volume was related to the difference of the
      vascularity. Some foctors originating in stromal cells might be involved in
      angiogenesis.

PMID- 11310490
TI  - Brain natriuretic peptide and cardiac rupture after acute myocardial infarction.
AB  - Cardiac rupture is a fatal complication in the acute stage of myocardial
      infarction (MI). However, no measures have yet been established to predict it.
      Herein we describe three MI patients with cardiac rupture in whom plasma brain
      natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations had
      been serially monitored from the onset of MI to cardiac rupture. In these cases,
      plasma BNP levels increased without symptomatic and hemodynamic changes and
      reached their highest level immediately before cardiac rupture, while plasma ANP
      levels remained unchanged. These cases suggest that the increased plasma BNP
      concentrations without symptomatic and hemodynamic changes may be a useful marker
      for predicting cardiac rupture after acute MI.

PMID- 11310491
TI  - Hemolytic uremic syndrome with intracranial hemorrhage following mitomycin C
      administration.
AB  - A 50-year-old woman treated for breast cancer with mitomycin C developed severe
      hypertension, followed by deep coma 3 days later. Computed tomography of the
      brain showed frontoparietal intracranial hemorrhage accompanied by subarachnoid
      hemorrhage. The patient was diagnosed additionally with hemolytic uremic syndrome
      (HUS) based on hemolytic anemia with schistocytosis, thrombocytopenia, and acute
      renal failure. The patient underwent hemodialysis and plasmapheresis with no
      improvement. We present the pathologic findings of the general vessels, which has
      been reported rarely. This case represents the first reported intracranial
      hemorrhage in HUS following mitomycin C administration. We emphasize the need to
      control blood pressure in patients with HUS.

PMID- 11310492
TI  - Sarcoidosis with granulomatous interstitial nephritis: report of three cases.
AB  - Three cases of sarcoidosis with granulomatous interstitial nephritis are
      reported. Patients were all male and over 50 years of age. They simultaneously
      had evidence of multiorgan involvement of sarcoidosis including lung and skin
      and/or eye. In addition, distinct features were found in each case: a
      granulomatous infiltration mimicking unilateral renal tumor (case 1); renal
      insufficiency solely due to granulomatous interstitial nephritis (case 2); and
      renal insufficiency with calcemic nephropathy and granulomatous interstitial
      nephritis (case 3). Prednisolone therapy resulted in disappearance of the
      pseudotumor in case 1 and partial improvement of renal function in cases 2 and 3.
      In cases 2 and 3, however, plasma creatinine did not return to normal values and
      a second renal biopsy in case 2 demonstrated residual interstitial fibrosis and
      few granulomas, suggesting that steroid therapy did not achieve complete reversal
      of changes.

PMID- 11310494
TI  - Invasive pulmonary aspergillosis with thrombosis in the left atrium.
AB  - We report a female patient with left atrial wall invasion from pulmonary
      aspergillosis. She had been treated for diabetes mellitus. Pulmonary
      aspergillosis extended to the left atrial wall via the left pulmonary vein and
      formed a polypoid lesion in the left atrium. The polypoid lesion was composed of
      thrombus, and the thrombus increased in size to become large, and it showed
      invagination into the mitral valve during diastole. We considered that the
      thrombus was formed on the injured endocardium. Severe invasive aspergillosis
      thus could occur in a mild systemic immunocompromised host.

PMID- 11310493
TI  - Pulmonary nocardiosis associated with idiopathic thrombocytopenic purpura.
AB  - A 69-year-old woman with idiopathic thrombocytopenic purpura, who was regularly
      followed and treated with prednisolone and danazol, was admitted to our hospital
      because of shortness of breath. Chest roentgenogram showed a large amount of left
      sided pleural effusion. Gram-positive branching rods, subsequently identified as
      Nocardia farcinica, were isolated from the fluid. Antibiotic treatment together
      with pleural drainage with an intercostal catheter resulted in complete remission
      of pyothorax. Pulmonary nocardiosis is a rare disease, but recognition of the
      disease in immunocompromised patients and the prompt initiation of appropriate
      treatments based on isolation of the pathogen can lead to a successful outcome.

PMID- 11310495
TI  - Cerebral atrophy and convulsive seizures after recovery from cerebral edema and
      coma in a patient with fulminant hepatitis B.
AB  - We report a 48-year-old woman who developed convulsive seizures and cerebral
      atrophy after recovery from fulminant hepatitis B with coma and cerebral edema at
      the acute stage. Neurological disturbances and cerebral signs are rare sequelae
      of fulminant hepatic failure (FHF); only a few cases have reported in the
      literature. Cortical laminar necrosis secondary to cerebral edema or delayed
      neuronal death due to toxic substances may have caused delayed brain atrophy and
      epileptogenesis.

PMID- 11310496
TI  - Recurrent cerebral embolism in a familial amyloid polyneuropathy patient who
      received partial liver transplantation from a living donor.
AB  - Cerebral embolism in relation to cardiac amyloidosis has not been widely noted. A
      47-year-old woman who had been suffering from familial amyloid polyneuropathy
      (FAP) for 7 years was treated with partial liver transplantation from a living
      donor and her early postoperative course was uneventful. During the 391st to
      613th postoperative day she experienced recurrent cerebral infarctions, but
      clinical examinations revealed no disorders capable of producing cerebral
      embolism. At autopsy splenic infarction and intracardiac thrombi adhering to the
      mitral valve and left atrium were found, and these areas showed severe amyloid
      deposition. Amyloid heart is considered to be one possible cause of systemic
      embolism.

PMID- 11310497
TI  - Overlap syndrome with cerebral hemorrhage caused by prostaglandin E1 infusion.

PMID- 11310498
TI  - In vitro loading of human synovial membrane with 5-hydroxydopamine: evidence for
      dense core secretory granules in type B cells.
AB  - Ultrastructural studies of the synovial membrane were performed on tissue samples
      obtained from the human lumbar facet joint. Ultrastructural changes in
      synoviocytes were studied after loading synovial samples with 5-hydroxydopamine
      (5-OHDA) in an oxygenated Krebs' solution, prior to fixation. Synoviocytes were
      set loosely in the intimal matrix and classified into type A (phagocytic) and
      type B (secretory) cells. In general, type A cells populated the surface of the
      synovial lining, whereas type B cells were located deeper in the tissue,
      extending a process into the synovial fluid. Type B cells in control samples
      contained sparse secretory granules. Free nerve endings were not found in the
      synovial intima. In response to incubation in 5-OHDA, a precursor of biogenic
      monoamines, synoviocytes clustered and established contact. The ultrastructure of
      type B cells in the loaded group clearly differed from controls. They possessed
      typical membrane-bound vesicles, containing an electron dense interior surrounded
      by a lucent space. The size of these dense core vesicles ranged from 100 to 260
      nm (on average 180 nm). They were in relation to microtubules and located
      preferentially in the marginal area of the cytoplasm, close to the Golgi complex.
      The ultrastructure of type A cells was not significantly altered. The present
      observations provide morphological evidence for the amine-handling properties of
      type B cells, indicating that they might be added to the list of 'APUD' cells of
      the diffuse neuroendocrine system. A recepto-secretory function for type B cells
      is discussed.

PMID- 11310499
TI  - Immunolocalization of keratan sulfate proteoglycan in rat calvaria.
AB  - We investigate, by the immunogold method, the localization of keratan sulfate
      (KS) proteoglycan in rat calvaria in order to clarify the detailed process of
      intramembranous ossification. KS was localized in bone nodules corresponding to
      calcified nodules, close to the saggital suture of calvaria. The immunoreactivity
      decreased in fully calcified regions distant from the suture. Electron
      microscopic observation revealed that KS was distributed in and around matrix
      vesicles, among collagen fibrils at the initial crystal deposition stage, and
      then concentrated in bone nodules. According to the progress of mineralization,
      KS tended to be localized in the peripheral region of the nodules. In addition,
      these nodules came in contact with collagen fibrils which also showed KS-positive
      reactivity. In cell organelles of osteoblasts, KS was detected in the Golgi
      apparatus. These findings suggest that osteoblasts in intramembranous
      ossification sites actively synthesize KS. KS in the calcified nodules, as well
      as other glycosaminoglycans in osteoid, may play an important role in additional
      and/or collagenous calcification by trapping calcium ions through its negative
      charge.

PMID- 11310500
TI  - Development of astrocytes in the mouse embryonic cerebrum tracked by tenascin-C
      gene expression.
AB  - The development of astrocytes in the rodent cerebrum has been considered to occur
      mainly in the perinatal stage after the end of neurogenesis, and the mode of
      generation and migration of the astroglial precursors in the embryonic cerebrum
      remains poorly understood. Tenascin-C (TN-C) is an astroglia-derived
      extracellular matrix molecule, and its expression can be traced to the
      ventricular germinative zone of the embryonic cerebrum. TN-C expression may
      therefore be used as a marker of astroglial precursors prior to the expression of
      the glial fibrillary acidic protein (GFAP), a marker for the late stage of
      astroglial differentiation. The development of astrocytes in the mouse embryonic
      cerebrum was examined by in situ hybridization histochemistry for TN-C mRNA as an
      early marker. Observations showed that TN-C-positive cells were aligned in the
      ventricular germinative zone and began to migrate radially at E (embryonic day)
      15. They were dispersed into the cortex as early as E17, and some were still in
      the DNA synthetic phase (S phase) even after lodgement in the cortex. TN-C
      positive cells differentiated into GFAP-immunopositive astrocytes in the cortical
      and subcortical areas at the neonatal stage. The distribution of their active
      generation sites in the ventricular germinative zone was not homogeneous but
      displayed a restricted pattern. The mode of their migration towards the cortical
      and subcortical areas also showed a characteristic pattern that correlated to the
      radial glial arrangement. These findings indicate that TN-C-positive cells
      represent a new subset of astroglial precursors which arise directly from the
      ventricular germinative zone, and that astrogliogenesis from this precursor
      occurs as early as the period of neurogenesis at the embryonic stage.

PMID- 11310501
TI  - Prevention of apoptosis of mammalian cells by the CED-3-cleaved form of CED-9.
AB  - CED-9 prevents apoptosis in embryonic cells of Caenorhabditis elegans but not in
      mammalian cells. We show here that the prevention of apoptosis in mammalian cells
      requires a CED-3-cleaved form (68-280) of CED-9 which is localized in the inner
      mitochondrial membrane. The viability of PC12 and HeLa cells was significantly
      increased after death stimuli when truncated CED-9 was expressed in these cells
      but full-length CED-9 did not. The truncated CED-9 expressed in these cells was
      largely localized to the inner mitochondrial and the endoplasmic reticulum
      membranes, while full-length CED-9 was detected mainly in endoplasmic reticulum
      fractions. Moreover, truncated CED-9 in purified mitochondria was resistant to
      trypsin digestion, but full-length CED-9 was not. These results suggest that the
      CED-3-cleaved form of CED-9 prevents apoptosis in mammalian cells by localizing
      to the inner mitochondrial membrane.

PMID- 11310502
TI  - Grafting of detergent-denatured skeletal muscles provides effective conduits for
      extension of regenerating axons in the rat sciatic nerve.
AB  - The basal laminae of muscle fibers, when treated by denaturing methods including
      freeze thawing, have been used as conduits for regenerating nerves. In this
      study, we developed a new method for denaturing skeletal muscle fibers through
      treatment with a biological detergent, sodium dodecyl sulfate. Laminin and type
      IV collagen proteins of muscle fiber basal laminae were preserved after the
      detergent treatment. A segment of detergent-denatured muscle was grafted to a 1
      cm defect of the rat sciatic nerve. One week after grafting, regenerating axons
      immunostained for neurofilaments were seen extending within laminin-positive
      muscle fiber basal lamina tubes. Four weeks after grafting, numerous myelinated
      axons at a much higher level than the control unoperated sciatic nerve, were
      found in the middle of the graft. They were smaller in diameter than those in the
      control nerve. Distal host nerves were well reinnervated 4 weeks after grafting.
      These findings suggest that the basal laminae of detergent-denatured muscle
      fibers provide effective conduits for regenerating axons.

PMID- 11310503
TI  - Arginine-vasopressin neurons in the rat hypothalamus produce neurokinin B and co
      express the tachykinin NK-3 receptor and angiotensin II type 1 receptor.
AB  - Secretion of arginine-vasopressin (AVP) from the hypothalamic paraventricular
      (PVN) and supraoptic (SON) nuclei is induced by neurokinin B (NKB) and
      angiotensin. To characterize the mechanisms by which this occurs, we used
      immunohistochemical techniques to assess the ability of AVP-producing neurons to
      express NKB, NKB receptor (NK-3 receptor) and angiotensin II type 1 receptor (AT
      1 receptor). Double fluorescence immunohistochemistry indicated that AVP
      immunoreactive cell bodies in the PVN and SON, as well as their axon varicosities
      in the posterior pituitary, co-express NKB. Almost all AVP-neuron perikarya also
      expressed both the NK-3 receptor and AT-1 receptor. Thus, AVP-producing neurons
      in the PVN and SON, which are regulated by NKB, are themselves a source of NKB.
      Furthermore, the regulation of AVP release by these neurons by NKB and
      angiotensin II is mediated by the NK-3 receptor and the AT-1 receptor,
      respectively.

PMID- 11310504
TI  - Intensely positively charged perineuronal nets in the adult rat brain as detected
      by staining with anionic iron colloid.
AB  - Ferric chloride, when boiled with ammonium thiocyanate, ammonia and cacodylic
      acid, is converted into a fine anionic iron colloid which consists of 1.0-1.5 nm
      electron dense granules and gives a distinct Prussian blue reaction (OHTSUKA and
      MURAKAMI, 1986). Light microscopy of tissue sections stained with this fine
      anionic iron colloid at pH values of 6.0, 7.0 and 8.0 showed that the healthy
      adult rat brain contains a considerable number of neurons which possess an
      intensely positively charged perineuronal net. This net was most clearly
      demonstrable by staining with the anionic iron colloid at a pH value of 8.0, at
      which ionizations of almost all cationic sites of the tissue elements were
      obliterated. Transmission electron microscopy of ultrathin sections stained at a
      pH value of 8.0 showed that the anionic iron colloid was preferentially deposited
      in the perineuronal tissue spaces. These findings indicate that the intensely
      positively charged perineuronal net contains some strongly basic substances such
      as guanidino compounds, and occupies the perineuronal (perisynaptic) tissue
      space.

PMID- 11310505
TI  - Arrangement of D-periodic collagen fibrils and association of proteoglycans with
      fibrils in the synovium of the mouse temporomandibular joint.
AB  - The present study was performed to examine changes in the arrangement of D
      periodic collagen fibrils in the synovium of the growing temporomandibular joint
      in mice. At 1 week of age, the mandibular condyle was undeveloped, and only a few
      collagen fibrils were recognizable in the subintimal layer of the synovium. At 8
      weeks, the mandibular condyle was structurally developed with an increase of
      collagen fibrils in the synovium; a fully mature condyle was observed at 6 months
      of age. The close association of proteoglycans with collagen fibrils in the
      synovium of the growing joint was examined by both conventional and energy
      filtering transmission electron microscopy of cupromeronic blue-stained
      specimens. Proteoglycans were associated with D-periodic collagen fibrils in the
      short filamentous form in random fashion at 1 week of age, but in a regular
      pattern with D-periodicity at 6 months. These associations in the synovium could
      be correlated with the mechanical character of the temporomandibular joint.

PMID- 11310506
TI  - Morphological changes in pancreatic islets of KATP channel-deficient mice: the
      involvement of KATP channels in the survival of insulin cells and the maintenance
      of islet architecture.
AB  - The ATP-sensitive potassium channel (KATP channel) is an essential ion channel
      involved in glucose-induced insulin secretion. The KATP channel is composed of an
      inwardly rectifying potassium channel, Kir6.2, and the sulfonylurea receptor (SUR
      1); in the pancreas it is reported to be shared by all endocrine cell types. A
      previous study by our research group showed that Kir 6.2-knockout mice lacked
      KATP channel activities and failed to secrete insulin in response to glucose, but
      displayed normal blood glucose levels and only mild impairment in glucose
      tolerance at younger ages. In some aged knockout mice, however, obesity and
      hyperglycemia were recognizable. The present study aimed to reveal morphological
      changes in pancreatic islets of Kir 6.2-knockout mice throughout life. At birth,
      there were no significant differences in the islet cell arrangement between the
      knockout mice and controls. At 14 postnatal weeks glucagon cells appeared in the
      central parts of islets, and this image became more pronounced with aging. In
      animals older than 50 weeks insulin cells decreased in numbers and intensity of
      insulin immunoreactivity; most islets in 70- and 80-week-old mice were
      predominantly composed of glucagon cells and peptide YY (PYY)-containing cells.
      Staining of serial sections and double staining of single sections from these old
      mice demonstrated the frequent coexpression of glucagon and PYY, which is a
      phenotype for the earliest progenitor cells of pancreatic endocrine cells. These
      findings suggest that the KATP channel is important for insulin cell survival and
      also regulates the differentiation of islet cells.

PMID- 11310507
TI  - Postnatal development of the retinal projection to the nucleus of the optic tract
      and accessory optic nuclei in the hooded rat.
AB  - Retinal projections to the nucleus of the optic tract (NOT) and accessory optic
      nuclei (AON) were studied in the postnatal hooded rat after monocular injection
      of cholera toxin B subunit (CTB) into the vitreous chamber of the eye. At all
      postnatal ages, retinal axons were labeled sensitively; they revealed dense
      projections to the contralateral, and sparse but distinct projections to the
      ipsilateral, NOT and AON. The CTB labeling enabled the first delineation of the
      complete morphology of developing retinal axons in the ipsilateral NOT and AON.
      From postnatal day (P) 1 to P3, axons with complex growth cones were seen, and
      unbranched collaterals with simple growth cones increased and extended gradually.
      At P6, complex growth cones disappeared while branched collaterals with simple
      growth cones as well as small-sized varicosities increased. By P12 (two days
      before eye-opening) the adult-like pattern of terminal arbors appeared. The
      branched collaterals with tiny, small-sized varicosities present probably
      represented developing synaptic boutons. At P16 (after eye opening), the pattern
      of terminal arbors was well developed, almost to the same extent as in the adult.
      By contrast, a broadly distributed, transient retinal projection around NOT and
      AON was gradually eliminated; it started to disappear during the first few
      postnatal days, and was fully retracted by the time of eye-opening time to a
      pattern normal for the adult.

PMID- 11310508
TI  - Immunolocalization of aquaporin-9 in rat hepatocytes and Leydig cells.
AB  - The aquaporin (AQP)-9 gene was recently isolated from human and rat liver cDNA
      libraries as a member of the water channel family for water and neutral solutes.
      Although the expression of AQP9 mRNA has been demonstrated in several organs
      including the liver and testis by Northern blot analysis, the cellular and
      subcellular localization of the AQP9 protein remains unclear. In the present
      light and electron microscopic immunohistochemical study, the localization of the
      AQP9 immunoreactivity was examined in fifteen kinds of rat organs using an
      antibody against rat AQP9 synthetic peptide. The antibody immunostained a major
      band of approximately 33 kDa in the liver by Western blot analysis.
      Immunoreactivity for AQP9 was found exclusively in the liver and testis among the
      organs examined. In the liver, positive staining appeared selectively along the
      space of Disse. Immunoelectron microscopy confirmed the localization of AQP9 on
      the surface of hepatocyte microvilli facing the space of Disse. In the testis,
      the plasma membrane of Leydig cells located between seminiferous tubules was
      conspicuously immunoreactive to the antibody. Intense mRNA expression was
      detected in the liver and testis but not in other organs by ribonuclease
      protection assay. These findings suggest a specific role for AQP9 in the
      transport of water and non-charged solutes in hepatocytes and Leydig cells.

PMID- 11310509
TI  - Specific localization of lysosomal aminopeptidases in type II alveolar epithelial
      cells of the rat lung.
AB  - We previously demonstrated that lysosomal cysteine proteinases, cathepsins B, H,
      and L were localized in lysosomes of alveolar macrophages and bronchial
      epithelial cells in the rat lung, while cathepsin H, a typical aminopeptidase,
      was additionally distributed in lamellar bodies containing surfactant in type II
      alveolar epithelial cells (ISHII et al., 1991). The present immunohistochemical
      study further examined the localization of lysosomal aminopeptidases, cathepsin
      C, and tripeptidyl peptidase I (TPP-I) in the rat lung. Western blotting
      confirmed the presence of cathepsin C and TPP-I as active forms in the pulmonary
      tissue, showing 25 kD and 47 kD, respectively. Immunohisto/cytochemical
      observations demonstrated that positive staining for cathepsin C and TPP-I was
      more intensely localized in alveolar epithelial regions than in bronchial or
      bronchiolar epithelial cells. By double immunostaining using confocal laser
      microscopy, immunoreactivity for cathepsin H was found to be co-localized with
      that for cathepsin C or TPP-I in both type II cells and macrophages. Moreover,
      when doubly stained with anti-cathepsin C and ED2, single-positive type II cells
      could be clearly distinguished from double-positive macrophages in the alveolar
      region. Immunoelectron microscopy revealed the gold labeling of cathepsin C or
      TPP-I in multivesicular and composite bodies, and lamellar bodies of Type II
      cells. These results showing that lysosomal aminopeptidases such as cathepsin H,
      cathepsin C and TPP-I are localized in lamellar bodies of type II alveolar
      epithelial cells strongly argue for the participation of lysosomal
      aminopeptidases in the formation process of surfactant containing specific
      proteins.

PMID- 11310510
TI  - Abortive secretion of an enamel matrix in the inner enamel epithelial cells
      during an enameloid formation in the gar-pike, Lepisosteus oculatus (Holostei,
      Actinopterygii).
AB  - The tooth in the gar-pike, Lepisosteus oculatus, an actinopterygian fish, is
      characterized by the occurrence of both enamel and enameloid, the former covering
      the tooth shaft and the latter, the tooth cap. Our previous research demonstrated
      that the enamel in this species was, as in the lungfish, immunoreactive for
      amelogenin, indicating its homologous nature with the mammalian tooth enamel,
      whereas the enameloid was completely immunonegative. The present study
      demonstrates that, during the early maturation stage of the enameloid formation,
      the inner enamel epithelial cells (IEECs) synthesize through a well-developed
      Golgi apparatus a fine-granular substance which is intensely immunoreactive for
      amelogenin. This substance was accumulated in a large saccule extended in a
      suprabasal zone of the cell; we were unable to find any morphological sign
      indicating a connection of the substance with the enameloid matrix. The abortive
      secretion of the enamel matrix-like substance in the IEEC during an enameloid
      formation was considered to be an instance of rudimental enamel formation. In the
      gar-pike, the synthesis of amelogenin in the IEEC has been demonstrated to occur
      independently from that of the enameloid matrix. The present findings demonstrate
      a prominent difference between the tooth enamel and enameloid.

PMID- 11310511
TI  - Manuscript peer review--a guide for health care professionals.
AB  - Peer review, in which peer experts assess the value of a manuscript submitted to
      a professional journal, is regarded as a crucial step in publication. It is
      generally agreed that its usefulness is highly dependent on the preparedness of
      each reviewer and quality of each assessment. With sustained growth in biomedical
      publications, more and more health professionals are being called on to serve as
      peer reviewers. An instructional framework should assist pharmacists and other
      health care professionals in conducting high-quality manuscript reviews.

PMID- 11310512
TI  - Post hoc power analysis: an idea whose time has passed?
AB  - Using a hypothetical scenario typifying the experience that authors have when
      submitting manuscripts that report results of negative clinical trials, the
      pitfalls of a post hoc analysis are illustrated. We used the same scenario to
      explain how confidence intervals are used in interpreting results of clinical
      trials. We showed that confidence intervals better inform readers about the
      possibility of an inadequate sample size than do post hoc power calculations.

PMID- 11310513
TI  - Therapeutic change of HMG-CoA reductase inhibitors in patients with coronary
      artery disease.
AB  - STUDY OBJECTIVE: To evaluate short-term outcomes when atorvastatin was
      substituted for pravastatin or simvastatin in patients with coronary artery
      disease. DESIGN: Open-label, fixed-dosage, one-way crossover from pravastatin and
      simvastatin to atorvastatin. SETTING: University-affiliated hospital and
      outpatient clinics. PATIENTS: Eighty patients with coronary artery disease with a
      minimum baseline low-density lipoprotein (LDL) above 130 mg/dl: 20 were treated
      with pravastatin 20 mg/day, 20 with pravastatin 40 mg/day, 20 with simvastatin 20
      mg/day, and 20 with simvastatin 40 mg/day for a minimum of 6 months, with a
      prescription refill rate of 80% or greater. Intervention. Before crossover,
      patients had a fasting lipid profile determined and were questioned about side
      effects of pravastatin and simvastatin. All patients were switched to
      atorvastatin 10 mg/day. After 12 weeks of atorvastatin therapy, a repeat fasting
      lipid profile was obtained and patients were questioned about side effects with
      the drug. MEASUREMENTS AND MAIN RESULTS: Baseline demographic and clinical
      characteristics of the treatment groups were not significantly different with the
      exception of a lower baseline LDL in patients receiving pravastatin 20 mg/day.
      Baseline LDL values were as follows: pravastatin 20 mg/day, 158+/-26 mg/dl;
      pravastatin 40 mg/day, 176+/-22 mg/dl; simvastatin 20 mg/day, 177+/-27 mg/dl; and
      simvastatin 40 mg/day, 177+/-27 mg/dl. Reductions in LDL after treatment with
      pravastatin or simvastatin were as follows: pravastatin 20 mg/day, 22%;
      pravastatin 40 mg/day, 32%; simvastatin 20 mg/day, 33%; and simvastatin 40
      mg/day, 38%. Patients achieving LDL goal with initial therapy were as follows:
      pravastatin 20 mg/day, 5%; pravastatin 40 mg/day, 5%; simvastatin 20 mg/day, 20%;
      and simvastatin 40 mg/day, 30%. After the switch to atorvastatin 10 mg/day,
      reductions in LDL were as follows: pravastatin 20 mg/day, 39% (p<0.001);
      pravastatin 40 mg/day, 38% (p<0.01); simvastatin 20 mg/day, 39% (p=0.04); and
      simvastatin 40 mg/day, 38% (p=0.83). Patients achieving LDL goals with
      atorvastatin 10 mg/day were as follows: pravastatin 20 mg/day, 60%; pravastatin
      40 mg/day, 30%; simvastatin 20 mg/day, 25%; and simvastatin 40 mg/day, 30%. The
      frequency of side effects was similar for all three statins. Based on annual
      average wholesale price, atorvastatin 10 mg/day was more cost-effective than all
      pravastatin and simvastatin regimens. CONCLUSIONS: Therapeutic interchange from
      pravastatin 20 and 40 mg/day and simvastatin 20 mg/day to atorvastatin 10 mg/day
      was associated with both cost savings and significant reductions in LDL. The
      change from simvastatin 40 mg/day to atorvastatin 10 mg/day was associated with
      cost savings and an equivalent reduction in LDL.

PMID- 11310514
TI  - Effectiveness and infant acceptance of the Rx medibottle versus the oral syringe.
AB  - STUDY OBJECTIVE: To compare the effectiveness and infant acceptance of drug
      delivery of the Rx medibottle with the standard oral syringe. DESIGN: Prospective
      open-label, randomized, crossover clinical study. SETTING: General pediatric
      outpatient clinic at an urban university. SUBJECTS: Thirty healthy, bottle-fed
      infants, aged 2-14 months, receiving routine vaccinations. INTERVENTION: Each
      infant received a single dose of acetaminophen (Tempra syrup), with one-half
      delivered by the Rx medibottle and one-half delivered with an oral syringe.
      MEASUREMENTS AND MAIN RESULTS: Three raters independently evaluated effectiveness
      and infant acceptance of each drug-delivery device. Effectiveness was based on
      the percentage of infants receiving 100% of the intended dose. Infant acceptance
      was scored using a validated infant medication acceptance scale (MAS, 10 =
      highest level). Significantly more infants received 100% of the intended dose
      with the Rx medibottle (93.3%) than with the oral syringe (56.7%, p=0.0074).
      Infants had a significantly higher mean MAS score when using the Rx medibottle
      (8.3+/-1.8 vs 7.3+/-1.7, p=0.002). In addition, a significantly higher percentage
      had ideal MAS scores of 9 or above with the Rx medibottle (73%) compared with the
      oral syringe (17%, p=0.0001). CONCLUSION: The Rx medibottle was more effective
      and had a higher level of infant acceptance than the oral syringe. Although
      further studies are necessary, this suggests that the Rx medibottle may be a
      better method of delivering liquid drug and may increase infant adherence.

PMID- 11310515
TI  - A comparison of the steady-state pharmacokinetics and safety of abacavir,
      lamivudine, and zidovudine taken as a triple combination tablet and as abacavir
      plus a lamivudine-zidovudine double combination tablet by HIV-1-infected adults.
AB  - STUDY OBJECTIVE: To investigate the steady-state pharmacokinetics of a triple
      combination tablet containing abacavir (ABC) 300 mg, lamivudine (3TC) 150 mg, and
      zidovudine (ZDV) 300 mg taken twice/day, and those of ABC 300 mg twice/day plus a
      double combination tablet containing 3TC 150 mg and ZDV 300 mg twice/day (ABC
      COM). DESIGN: Open-label, crossover study. SETTING: Two hospital-based clinical
      research units. PATIENTS: Twelve men infected with human immunodeficiency virus
      1. INTERVENTION: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were assessed
      after dosing with ABC-COM and the triple combination tablet. MEASUREMENTS AND
      MAIN RESULTS: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were similar for
      the triple combination tablet versus ABC-COM for the following: geometric mean
      (GM) area under the serum concentration-time curve, ABC 6.08 versus 5.87, 3TC
      5.51 versus 5.53, and ZDV 1.38 versus 1.46 microg x hr/ml; GM maximum serum
      concentration (Cmax-ss), ABC 3.09 versus 3.19, 3TC 1.26 versus 1.40, and ZDV 1.19
      versus 1.15 microg/ml; median time to Cmax-ss, ABC 0.75 versus 0.75, 3TC 1.50
      versus 1.24, and ZDV 0.75 versus 0.75 hours; and GM oral clearance, ABC 51 versus
      49, 3TC 27 versus 27, and ZDV 217 versus 206 L/hour. The GM half-lives of ABC and
      ZDV were similar for both treatments, 1.69 versus 1.58 and 2.30 versus 2.08
      hours, respectively. CONCLUSION: Steady-state pharmacokinetics of ABC, 3TC, and
      ZDV were similar in patients who took them as ABC-COM or as a triple combination
      tablet.

PMID- 11310516
TI  - Confirming the reliability of the sedation-agitation scale administered by ICU
      nurses without experience in its use.
AB  - STUDY OBJECTIVES: To determine the validity and reliability of the Sedation
      Agitation scale (SAS) when administered by intensive care unit (ICU) nurses with
      no experience in its use. DESIGN: Prospective, psychometric evaluation. SETTING:
      Adult medical-cardiac ICU. PATIENTS: Sixty patients. INTERVENTION: Sedation and
      agitation were observed simultaneously but independently by nurses and two
      investigators, and patients were rated with the SAS. The assessment of an
      experienced clinical nurse specialist was recorded on visual analog scales (VAS)
      for sedation (VAS-S) and agitation (VAS-A). MEASUREMENTS AND MAIN RESULTS: The
      SAS scores of ICU staff nurses were compared with VAS scored by the clinical
      nurse specialist using Pearson correlation coefficient. The SAS correlated well
      with VAS-S (Spearman's p = -0.77, p<0.001). Neither SAS nor VAS-A was correlated
      (Spearman's p = 0.05, p>0.5), but there were few observations of agitated
      patients. The SAS interrater agreement was excellent between the two trained
      investigators (weighted K = 0.93, p<0.001) and between investigators and staff
      nurses (weighted K = 0.85 and 0.87, p<0.001 for both). CONCLUSION: The SAS is
      reliable when administered by staff nurses with no experience with it. Due to the
      paucity of observations of agitated patients, we were unable to determine its
      validity for assessing agitation.

PMID- 11310517
TI  - Evaluation of electrocardiographic and hemodynamic effects of caffeine with acute
      dosing in healthy volunteers.
AB  - STUDY OBJECTIVE: To evaluate the effects of moderate, single-dose caffeine
      consumption on electrocardiographic variables: PR, QRS, QT, QTc, and RR
      intervals, and QT and QTc interval dispersion. Effects of caffeine on blood
      pressure and heart rate also were evaluated. DESIGN: Randomized, double-blind,
      placebo-controlled, crossover study. SETTING: University school of pharmacy.
      PATIENTS: Ten healthy volunteers aged 17 years or older. INTERVENTION:
      Participants abstained from caffeinated products for at least 2 days before the
      study began and were randomly designated to receive placebo or caffeine 400 mg on
      various days. For each of the study phases, a baseline 12-lead electrocardiogram
      (ECG) was performed and a subsequent 12-lead ECG performed 3 hours after
      ingesting the study drug. Blood pressure readings were taken with each ECG.
      MEASUREMENTS AND MAIN RESULTS: No significant changes in any intragroup or
      intergroup electrocardiographic variables occurred. Caffeine increased blood
      pressure (systolic blood pressure [SBP]/diastolic blood pressure [DBP]) from
      118+/-5/75+/-6 mm Hg to 128+/-8/77+/-7 mm Hg versus baseline (p=0.0022 and
      p=0.0368 for SBP and DBP, respectively). After drug dosing, SBP in the caffeine
      group was significantly higher than in the placebo group (128+/-8 mm Hg versus
      119+/-7 mm Hg, p=0.0174). CONCLUSION: Moderate caffeine consumption by healthy
      young adults does not acutely affect PR, QRS, QT, QTc, and RR intervals, or QT
      and QTc interval dispersion. Caffeine-naive subjects experienced persistent
      elevations in SBP and DBP 3 hours after caffeine ingestion, indicating that
      longer caffeine abstinence than that which is recommended is necessary for blood
      pressure determination in the clinical setting.

PMID- 11310518
TI  - Individualized pharmacokinetic monitoring results in less aminoglycoside
      associated nephrotoxicity and fewer associated costs.
AB  - STUDY OBJECTIVE: To examine the impact of individualized pharmacokinetic
      monitoring (IPM) on the development of aminoglycoside-associated nephrotoxicity
      (AAN). DESIGN: Retrospective case-control study. SETTING: Two teaching hospitals.
      SUBJECTS: Two thousand four hundred five patients who received aminoglycosides.
      INTERVENTION: Aminoglycoside therapy dosed by either IPM or physicians'
      directions. MEASUREMENTS AND MAIN RESULTS: Patients receiving IPM were
      significantly less likely to develop AAN by both univariate (7.9% vs 13.2%,
      p=0.02) and multivariate methods (odds ratio 0.42, p=0.002). Female sex was
      protective against AAN. Age 50 years and above, high initial aminoglycoside
      trough, long duration of therapy, and concurrent piperacillin, clindamycin, or
      vancomycin increased risk of AAN. We estimated that IPM decreased AAN costs by
      $90,995/100 patients. CONCLUSION: Individualized pharmacokinetic monitoring
      significantly decreased the frequency of AAN and its associated economic costs.

PMID- 11310519
TI  - Antithrombotic drugs for secondary stroke prophylaxis.
AB  - Stroke is the third most common cause of adult mortality in the United States.
      Antithrombotic agents form the mainstay of stroke prevention. Aspirin produces a
      modest reduction in the risk of second stroke and is widely recommended for
      initial therapy. The thienopyridines ticlopidine and clopidogrel are alternatives
      for secondary prevention in patients who do not respond to or cannot take
      aspirin. They are no more effective than aspirin and have been associated with
      thrombotic thrombocytopenic purpura. The combination of aspirin and extended
      release dipyridamole has several mechanisms of action and an additive effect on
      reducing stroke risk compared with either agent alone. A 2-fold increase in risk
      reduction and favorable safety profile suggest that the combination can serve as
      first-line prophylaxis against a second stroke.

PMID- 11310520
TI  - Urogenital atrophy: prevention and treatment.
AB  - Fifteen percent of premenopausal women, 10-40% of postmenopausal women, and 10
      25% of women receiving systemic hormone therapy experience urogenital atrophy.
      The most common symptoms are dryness, burning, pruritus, irritation, and
      dyspareunia. Estrogen loss, drugs, and chemical sensitivities are causes.
      Estrogen or hormone replacement therapy (ERT-HRT) is the treatment of choice in
      postmenopausal women. Dosages prescribed for menopause symptoms or to prevent
      osteoporosis (and, potentially, other conditions) can restore the vagina to
      premenopausal physiology and relieve symptoms. Concomitant progestins are
      necessary for women with an intact uterus to minimize or eliminate estrogen
      induced endometrial cancer. Low-dosage oral and vaginal ERT can relieve
      urogenital atrophy but might not produce systemic effects. Progestins are not
      necessary with vaginal rings and vaginal tablets. If ERT is given only to treat
      urogenital atrophy, estrogen creams 1 or 2 times/week may prevent recurrence
      after symptoms are resolved. Progestins are not required for occasional estrogen
      cream use. Vaginal moisturizers provide longer relief by changing the fluid
      content of endothelium and lowering vaginal pH. Vaginal lubricants provide short
      term relief. Women with contraindications to ERT-HRT could use lubricants for
      intercourse-related dryness or moisturizers for more continuous relief. The lay
      press promotes agrimony, black cohosh, chaste tree, dong quai, witch hazel, and
      phytoestrogens for vaginal dryness and dyspareunia; however, no evidence exists
      to support these specific claims. Pharmacists should be actively involved in
      identifying, preventing, and treating urogenital atrophy.

PMID- 11310521
TI  - Evaluation of the antihyperlipidemic properties of dietary supplements.
AB  - We reviewed the published literature regarding the antihyperlipidemic effects of
      dietary supplements. A search of MEDLINE database, EMBASE Drugs and Pharmacology
      database, and the Internet was performed, and pertinent studies were identified
      and evaluated. References from published articles and tertiary references were
      used to gather additional data. Published trials indicate that red yeast rice,
      tocotrienols, gugulipid, garlic, and soy protein all have
      antihypercholesterolemic effects. These supplements, as well as omega-3 fatty
      acids, also have antihypertriglyceridemic effects. In clinical trials none of the
      agents led to a reduction in low-density lipoproteins greater than 25%,
      suggesting modest efficacy. When recommending these supplements, clinicians
      should keep in mind that their long-term safety is not established and patients
      should be monitored closely.

PMID- 11310522
TI  - Safety and effectiveness of ibutilide in a community hospital.
AB  - To determine the safety and effectiveness of ibutilide, we conducted a
      retrospective study of patients in a community hospital from December 1997
      January 2000, reviewing hospital and pharmacy records for 12 inpatients (aged
      68+/-13 yrs) receiving ibutilide for atrial fibrillation or flutter. The
      cumulative conversion rate with ibutilide 0.012+/-0.004 mg/kg was 58%. Serious
      cardiovascular adverse events were documented in six patients; of those patients,
      five had baseline QTc intervals above 440 msec, two experienced ventricular
      fibrillation, and four experienced symptomatic bradycardia (range 49-60
      beats/minute) requiring medical intervention. The effectiveness of ibutilide was
      similar to that found in previous studies. However, more complications were seen
      in this setting where ibutilide was used infrequently and without stringent
      patient selection criteria or standardized administration protocols. To ensure
      optimal patient care, institutions should consider implementing guidelines or
      education strategies to reduce the potential for serious adverse effects
      associated with improper screening, dosing, and monitoring of patients receiving
      ibutilide.

PMID- 11310523
TI  - Idiosyncratic rifabutin-induced leukopenia and SIADH: case report and review.
AB  - Rifabutin is increasingly critical for treatment of atypical mycobacterial
      infections. One of its serious adverse effects is leukopenia. When encountering
      rifabutin-induced leukopenia, clinicians are faced with the dilemma of whether to
      lower the dosage of rifabutin or discontinue it because existing literature does
      not indicate whether rifabutin-induced leukopenia is dose related or
      idiosyncratic. We report the first established case of idiosyncratic rifabutin
      induced leukopenia in an immunocompetent man treated for pulmonary Mycobacterium
      avium complex infection. The patient also developed rifabutin-induced syndrome of
      inappropriate antidiuretic hormone (SIADH), which also has not been previously
      reported.

PMID- 11310524
TI  - Selective serotonin reuptake inhibitors for aggressive behavior in patients with
      dementia after head injury.
AB  - Head injury of any severity can result in acute and chronic neuropsychiatric
      symptoms. After head injury, aggressive behaviors can be disabling to victims and
      stressful to their families. When aggression is compounded by dementia, treatment
      can be more difficult. Psychotropic agents can attenuate aggressive behaviors
      associated with mental disorders. Three patients with dementia and chronic
      aggression after head injury responded favorably to selective serotonin reuptake
      inhibitors.

PMID- 11310525
TI  - Possible atypical cross-sensitivity between phenytoin and carbamazepine in the
      anticonvulsant hypersensitivity syndrome.
AB  - Anticonvulsant hypersensitivity syndrome (AHS) is a rare but potentially life
      threatening reaction that occurs in response to common anticonvulsants in
      predisposed individuals. It is often characterized by fever, rash,
      lymphadenopathy, hepatitis, and laboratory abnormalities. Consequently, it often
      is overlooked or even misdiagnosed by practitioners unfamiliar with AHS. Cross
      sensitivity manifests frequently between phenytoin, phenobarbital, and
      carbamazepine as an exacerbation of presenting signs and symptoms. We report a
      case of AHS in a patient whose clinical features changed significantly when
      switching from phenytoin to carbamazepine. Physicians and pharmacists must become
      aware of the extreme variability in AHS manifestation so that the offending
      anticonvulsant regimen can be discontinued in a timely manner.

PMID- 11310526
TI  - Vasopressin and blood pressure support for pancreatitis-induced systemic
      inflammatory response syndrome with circulatory shock.
AB  - A 54-year-old patient, admitted to the intensive care unit with a diagnosis of
      severe pancreatitis, developed circulatory shock that failed to respond to
      standard vasopressor treatment: epinephrine and norepinephrine. Addition of
      vasopressin helped reduce standard catecholamine need while maintaining adequate
      arterial blood pressure. Vasopressin appears to be a promising agent for
      maintaining arterial pressure during septic shock or systemic inflammatory
      response syndrome, but due to limited data and potential side effects, its use as
      first-line treatment for these indications is not recommended.

PMID- 11310527
TI  - Potential interaction between warfarin and boldo-fenugreek.
AB  - A patient was treated with warfarin for atrial fibrillation. During treatment, an
      increase in international normalized ratio (INR) and her admission that she was
      taking a variety of natural products, to include boldo and fenugreek, led us to
      suspect that some of these natural products could alter the effect of warfarin.
      When she stopped the culpable products, the INR returned to normal after 1 week.
      The herb-drug interaction was observed a second time after both products were
      reintroduced a few days later. The imputability of this interaction to both
      natural products, as determined by the Naranjo algorithm, suggests a probable
      association between boldo-fenugreek and increased bleeding time in patients
      treated with warfarin. No undesirable reaction was reported during telephone
      discussions with the patient. Nevertheless, we recommend that clinicians treating
      patients with anticoagulant therapy be vigilant when patients also take herbal
      agents.

PMID- 11310528
TI  - Colestipol-induced hepatotoxicity.
AB  - A 65-year-old man with type IIa dyslipidemia who received flavored colestipol
      granules 2 scoops/day for 3 months developed asymptomatic hepatotoxicity. Several
      of his liver enzymes were elevated 10 times the upper limit of normal. One week
      after discontinuing colestipol, serum transaminases fell dramatically, with some
      returning to normal limits. Four weeks after colestipol was discontinued, all
      liver function tests were normal. Rechallenge was not attempted. Other potential
      causes of hepatocellular injury were evaluated. Bile acid-binding resins commonly
      are administered to treat type IIa dyslipidemia. Despite extensive use of the
      resins, significant elevations of transaminase levels are rare. Because the exact
      mechanism of bile acid resin-induced hepatotoxicity is unknown, high-risk
      patients may require liver function test monitoring and education on hepatotoxic
      side effects.

PMID- 11310529
TI  - Important changes in the treatment of epilepsy.

PMID- 11310530
TI  - Do alignment thresholds define a critical boundary in long-range detection
      facilitation with co-linear lines?
AB  - Thresholds for line contrast detection (experiment 2) were measured with a two
      alternative temporal forced-choice procedure as a function of the spatial
      position of a vertical target line with regard to two co-linear context lines.
      The different spatial positions of the target line corresponded to values near
      the position discrimination threshold (experiment 1) reflecting the just
      detectable lateral offset, or non-co-linearity, between the context lines which
      were vertically separated by about 100 minutes of visual arc. Target and context
      lines were vertically separated by about 30 minutes of arc, had equal contrast
      polarity in one case, and opposite contrast polarity in the other. Strong line
      contrast detection facilitation is found at perceptually co-linear target
      locations. This facilitation decreases noticeably at a horizontal target offset
      that corresponds to the alignment threshold measured with the context lines. The
      effects are independent of the relative contrast polarity of target and context
      and, as shown in a third experiment, also independent of both the relative length
      or number of lines, and the magnitude of their absolute co-axial separation. This
      independence seems to hold, provided individual line length and co-axial distance
      between lines are larger than what appears to be the lower limit of the long
      range spatial domain for orientation or contour integration (i.e. 20 minutes of
      arc), as determined by previous studies. The findings reported here suggest that
      alignment thresholds are likely to define a critical lateral boundary in long
      range detection facilitation with co-linear lines. They support models of contour
      integration based on interactions between neural mechanisms that integrate local
      signals of contrast, orientation, and relative position or end-to-end alignment.
      Such mechanisms may help to explain the formation of representations of virtual
      contours and object contours in human perception.

PMID- 11310531
TI  - The influence of two-dimensional stimulus properties in a reconstruction task
      with minimal information stimuli.
AB  - Effects of viewpoint that are typically found in shape recognition tasks have
      been interpreted in the past as strong evidence against approaches based on the
      use of geometric invariants by the human visual system. At first sight, the use
      of such invariants would indeed predict shape recognition to be viewpoint
      independent. It has been argued before, however, that the visual estimation of
      invariants need not itself be invariant. Changes of viewpoint introduce changes
      in 2D stimulus features. The latter may make the estimation of invariants by the
      visual system more or less difficult. The present study explores how such 2D
      features influence estimation distributions in a reconstruction paradigm.
      Subjects were shown four coplanar dots. They were asked to estimate the position
      of one of the dots relative to the three others on the basis of a slanted version
      of the configuration. An estimation distribution was obtained for every position
      of the dot to be estimated. Biases in these distributions indicated that subjects
      performed the task by using 2D reference axes that were unambiguously
      identifiable in both the images of the dot pattern.

PMID- 11310532
TI  - Regional sensitivity for shape discrimination.
AB  - In a task where subjects had to detect smooth deviations from circularity, we
      assessed whether performance varied with eccentricity. Our stimuli were circular
      4th derivatives of Gaussian contours (CD4s) whose radii were sinusoidally
      modulated. We used D4s of different peak spatial frequencies and overall
      diameters. Although performance declined with eccentricity for all radial
      frequencies tested, once scaling was taken into account, sensitivity was similar
      at all eccentricities. This was the basis of the scale-invariance also exhibited
      by this task. Thus, shape discrimination does not appear to be a specialized
      function limited to central vision.

PMID- 11310533
TI  - Collinear interactions and contour integration.
AB  - The visibility of a local target is influenced by the global configuration of the
      stimulus. Collinear configurations are a specific case in which facilitation or
      suppression of the target has been found to be dependent on the contrast
      threshold of the target. The role of collinear interactions in perceptual
      grouping, especially in contour integration, is still controversial. In the
      current study, the role of collinear interactions in noise was investigated using
      experimental conditions similar to those utilized in studies of contour
      integration. The contrast detection paradigm in the presence of similar Gabor
      elements presented in the background was used. The results show that contrast
      detection threshold of the target alone is increased (suppression) when it is
      embedded in randomly oriented background elements. However, when the target is
      flanked by two collinear Gabor elements, the target is facilitated even at higher
      target contrast levels. Facilitation is not found for orthogonal configurations.
      The results suggest that the response to a local element in a contour is modified
      by lateral facilitative and suppressive inputs from elements comprising the
      smooth contour and randomly oriented background elements, respectively. Thus,
      detection of elements along a contour should be considered as integration of
      global neuronal activity rather than as the output of local and individual
      neurons.

PMID- 11310534
TI  - Contrast dependence of perceptual grouping in brain-damaged patients with visual
      extinction.
AB  - Extinction is manifested in conditions of bilateral simultaneous stimulation, as
      a failure to detect the stimulus contra-lateral to the side of a cerebral lesion,
      while the same stimulus is correctly detected there when presented in isolation.
      The phenomenon is usually interpreted in terms of impaired mobilization of
      attention from an attended to an unattended object. We have recently shown, using
      pairs of Gabor patches as stimuli, that pair detection is maximally improved in
      conditions where the two stimuli presented simultaneously to the two halves of
      the visual field are co-oriented and co-axial and their location is not too
      eccentric. Here we add new information by showing that contrast isotropy of the
      stimulus pair is important in producing this orientation-similarity gain. The
      further advantage of co-oriented co-linear stimuli over co-oriented parallel
      (vertical) stimuli was shown exclusively with iso-contrast stimulus pairs, and
      was significantly enhanced when the contrast level of the stimulus pair was low.
      Stimulus properties producing reduced extinction seem to correlate with the
      selectivity pattern and contrast dependence of (a) spatial lateral facilitation
      observed in psychophysical studies with normal observers, and (b) long-range
      interactions observed in the primary visual cortex. Thus, two remote visual
      stimuli seem to be processed as a single object when the corresponding neuronal
      activities are linked via long-range lateral interactions. The present
      demonstration of contrast dependency in such processing, strengthens our previous
      conjecture that even in the presence of significant, extinction producing,
      parietal damage, the primary visual cortex preserves the capacity to encode,
      using long-range lateral interactions, an image description in which visual
      objects are already segregated from background.

PMID- 11310535
TI  - Dichoptic plaids may rival, but their motions can integrate.
AB  - When the eyes view incompatible images, binocular rivalry usually results: image
      constituents in corresponding parts of the monocular visual fields are not
      perceived simultaneously. We asked naive undergraduates to view dichoptic,
      dioptic, and monoptic plaids. The dichoptic images evoked strong binocular
      rivalry when contrast was high, especially if the component gratings were set in
      motion. Nevertheless, the subjects' visual systems integrated the motion
      information across the two eyes, producing a unitary motion percept that did not
      reflect the image in either eye alone. By manipulating the relative spatial scale
      of the gratings, we affected how well the motion cohered: the results were
      remarkably similar between dichoptic and traditional dioptic plaids. By
      manipulating the relative speed of the gratings, we systematically affected the
      perceived direction of motion of the plaids; these results were also remarkably
      similar for dichoptic and dioptic plaids. Thus, the motion analysis of dichoptic
      and dioptic plaids is proceeding according to very similar rules, even though the
      dichoptic images are incompatible and evoke binocular rivalry.

PMID- 11310536
TI  - Optimal setups for forced-choice staircases with fixed step sizes.
AB  - Forced-choice staircases with fixed step sizes are used in a variety of formats
      whose relative merits have never been studied. This paper presents a comparative
      study aimed at determining their optimal format. Factors included in the study
      were the up/down rule, the length (number of reversals), and the size of the
      steps. The study also addressed the issue of whether a protocol involving three
      staircases running for N reversals each (with a subsequent average of the
      estimates provided by each individual staircase) has better statistical
      properties than an alternative protocol involving a single staircase running for
      3N reversals. In all cases the size of a step up was different from that of a
      step down, in the appropriate ratio determined by Garcia-Perez (Vision Research,
      1998, 38, 1861 - 1881). The results of a simulation study indicate that a) there
      are no conditions in which the 1-down/1-up rule is advisable; b) different
      combinations of up/down rule and number of reversals appear equivalent in terms
      of precision and cost: c) using a single long staircase with 3N reversals is more
      efficient than running three staircases with N reversals each: d) to avoid bias
      and attain sufficient accuracy, threshold estimates should be based on at least
      30 reversals: and e) to avoid excessive cost and imprecision, the size of the
      step up should be between 2/3 and 3/3 the (known or presumed) spread of the
      psychometric function. An empirical study with human subjects confirmed the major
      characteristics revealed by the simulations.

PMID- 11310537
TI  - Comments on ultra-high-resolution STEM.
AB  - The resolution of an image in a scanning transmission electron microscope may be
      improved if an image of the specimen is recorded for each point in the
      nanodiffraction pattern. It is shown that the method suggested by Rodenburg et
      al. (Ultramicroscopy 48 (1993) 304) may serve as the basis for an experimentally
      feasible scheme in which a resolution of better than 0.1 nm is achieved for
      regions of 1 nm diameter chosen from normal STEM images.

PMID- 11310538
TI  - Coated silica tips for use in high-pressure, high-temperature, scanning tunneling
      microscopy.
AB  - A novel application of coated silica tips for use in high-pressure, high
      temperature, scanning tunneling microscopy is introduced. Thermal drift is
      reduced in the Z-direction due to the low thermal expansion of silica. Virtually,
      any conducting material that can be evaporated or sputtered can be used as a tip
      material. Experimental results are shown for tips sputter coated with platinum,
      along with images obtained.

PMID- 11310539
TI  - Dark field X-ray microscopy: the effects of condenser/detector aperture.
AB  - In order to visualize the functionality of a biological cell, it is often
      desirable to label specific proteins. In this work we concentrate on the optical
      theory of visualizing colloidal gold labels with soft X-ray microscopes, where
      scattering from small gold spheres used as labels dominates the image. Using
      numerical simulations of bright and dark field imaging, we compare different
      configurations of condenser and objective lenses in transmission X-ray
      microscopes, and configurations of detector and objective lens in scanning
      transmission X-ray microscopes. It is verified that the contrast of small,
      closely spaced features is strongly affected by changes in these configurations;
      the optimum situation is to have the condenser aperture (in TXM) or detector
      aperture (in STXM) equal to 3/2 that of the objective numerical aperture.

PMID- 11310540
TI  - Electric charging of thin films measured using the contrast transfer function.
AB  - The phase shift of electron waves due to charging of thin films is investigated
      using the contrast transfer properties of the microscope. We take two photos, one
      with film at the back focal plane and the other one without film. The phase
      difference between the contrast transfer functions of the two photos is evaluated
      using our theoretical predictions. The theoretical model is based on an
      analytical solution of the Laplace equation with appropriate boundary conditions.
      From the resulting electrostatic potential function the phase shift of electron
      waves is derived in a weak lens approximation. With this method, information
      about the radius of the electron beam and the magnitude of the electrostatic
      potential at the thin film is obtained. The excellent agreement between the
      theoretical model and experimental results is observed.

PMID- 11310541
TI  - Crystal thickness and extinction distance determination using energy filtered
      CBED pattern intensity measurement and dynamical diffraction theory fitting.
AB  - A new method for measuring thickness and extinction distance of single crystals
      based on computed adjustment of measured and calculated CBED pattern intensity
      profiles is presented and discussed. The experimental beam intensity distribution
      is measured from an energy filtered CBED pattern recorded on a CCD camera. The
      calculated profile is based on dynamical diffraction theory, and with the two
      beam approximation the analytical expression contains only two free parameters:
      specimen thickness t and extinction distance xig. Parameter refinement through
      minimization of the difference between experimental and calculated intensity
      profiles is carried out using Origin 5.0 software from Microcal. The iterative
      procedure always converges to a unique solution in a few seconds, yielding an
      accurate value for both thickness and extinction distance. The method is
      extensively tested on silicon using the (0 0 4) Bragg reflection. On specimens in
      the usual TEM thickness range, the method gives result similar to the
      conventional (P.M. Kelly et al., Phys. Stat. Sol. A31 (1975) 771; S.M. Allen,
      Philos. Mag. A 43 (1981) 325) graphical methods, both based on the measurement of
      fringe spacing. Moreover, it is shown that the calculation matches perfectly both
      the positions of the minimums and maximums as well as the amplitude of maximums.
      For any single intensity profile, specimen thickness and extinction distance can
      be determined with a precision of about 0.2%. A statistical comparison of our
      method with the Kelly and Allen techniques, based on more than 50 experiments,
      shows an improvement in measured extinction distance dispersion. Using 197 keV
      electrons, and liquid-nitrogen cryo-holder, the new technique yields an
      experimental value of 161+/-3 nm for the extinction distance for silicon with the
      (0 0 4) Bragg reflection. The equivalent tabulated value at 0 K is about 156 nm.
      Using the Kelly and Allen methods, the extinction distance is found to be 162+/-6
      nm. The improvement in precision is a direct consequence of matching the
      intensity profile envelope, which contains information on the extinction
      distance. Also the accuracy of thickness determination is improved and is around
      0.5 to 1% for common specimen thickness. The minimum measurable sample thickness
      is shown to be two to three times thinner than with the Kelly and Allen methods
      (0.3 xig, as opposed to 0.8 xig). With no independent calculation of the
      extinction distance needed, the method is also applicable on unknown crystals.
      The method is fast, simple and can be easily automated.

PMID- 11310542
TI  - Accurate length determination of DNA molecules visualized by atomic force
      microscopy: evidence for a partial B- to A-form transition on mica.
AB  - Achieving the most correct estimate of the contour length of digitized DNA
      molecules is a key aspect of the microscopic analysis of nucleic acids by either
      electron microscopy (EM) or atomic force microscopy (AFM). Six different methods,
      that are mathematically not too complex and suited for common, practical use,
      have been tested here using simulated polymers in two dimensions and real DNA
      molecules (564, 1054, 2049 and 4297 bp long) imaged in air by AFM. The main
      result is that the frequently used Freeman estimator (L(F) = n(e) + square root
      2n(o)) overestimates the real contour length of the polymers by about 4%. More
      accurate estimates are obtained with the Kulpa estimator (L(K) = 0.948n(e) +
      1.343n(o)) or with the corner count estimator (L(C) = 0.980)n(e) + 1.406n(o) -
      0.091n(c)). In the range of the DNA sizes and magnifications we have considered,
      however, the best results are obtained with an ad hoc developed routine that
      smoothes the DNA trace by a polynomial fitting of degree 3 over a moving window
      of 5 points. Under these conditions, the difference between the measured and the
      real contour length of the molecules is less than 0.4%. The accuracy of this
      procedure allowed us to reveal a discrete, size-dependent, shortening of DNA
      molecules deposited onto mica under low salt conditions and imaged in air by AFM.
      Awareness of this structural alteration, that can be attributed to a partial
      transition from B- to A-form DNA, may lead to a more correct interpretation of
      DNA molecules or protein-DNA complexes imaged by AFM.

PMID- 11310543
TI  - Semi-automatized processing of AFM force-spectroscopy data.
AB  - Atomic force microscopy operated in the force-spectroscopy mode is now a
      widespread technique, often used to investigate ligand-receptor interactions with
      the goal of measuring forces at the individual molecule level. However, in an
      experiment, the simultaneous interaction of several ligand/receptor pairs cannot
      be excluded. This may produce complicated force curves, although unambiguous
      ruptures are sometimes observed. In the case of the non-specific adhesion of
      molecules, such as fibrinogen, to a surface, it is usually difficult to identify
      the real events on the force curves. This can render the application of fixed
      rules uneasy and in addition can introduce some degree of arbitrariness if the
      analysis has to be performed by hand. In the present paper a computer algorithm,
      aimed at speeding up the processing, and at applying selection rules in a
      reproducible manner, is proposed. It is applied to force recordings performed at
      various retraction velocities, thus various loading rates. The influence on the
      evaluation of the rupture forces of the different parameters that can be set by
      the operator is discussed.

PMID- 11310544
TI  - High-angle annular dark-field imaging of self-assembled Ge islands on Si(0 0 1).
AB  - Low-resolution high-angle annular dark-field (HAADF) imaging is applied to the
      study of coherent Ge islands on a Si(0 0 1) substrate. Experimental HAADF images
      reveal a complicated pattern for a coherent Ge island under (0 0 1) zone axis
      conditions due to strain-induced interband scattering between different Bloch
      wave branches. This complicated pattern varies with objective aperture size and
      defocus because of the effect from the depth of field. This suggests that the
      strain field of a coherent Ge island can be mapped out in 3 dimensions using
      HAADF imaging. When samples are tilted away from dynamical conditions, image
      contrast agrees with the predictions from atomic number variation (Z contrast).
      Therefore, quantitatively compositional analysis is feasible under kinematical
      imaging conditions when strain contrast is suppressed. Simulations using multi
      beam Bloch-wave theory agree well with the experimental images on the complicated
      strain-induced and through-focus images.

PMID- 11310545
TI  - Determination of the orientation in small areas of the exit wave.
AB  - Local differences in thickness and misorientation in a through-focus
      reconstructed exit wave hamper direct interpretation. These local thicknesses and
      misorientations can be refined on an atomic scale using the intensities of the
      Fourier components with the refinement procedure in which a least-squares
      refinement is combined with a multi-slice calculation. The method was applied to
      the superconductor La3Ni2B2N3. The crystal tilt and specimen thickness can be
      determined with an R-value of 8-25%, with a better R-value for thinner areas.
      Significant differences in the refined tilts, thicknesses and R-values are
      observed when reconstructed exit waves that are corrected for mechanical
      vibration are compared with reconstructed exit waves, which are uncorrected.

PMID- 11310546
TI  - Exercise-induced myocardial ischaemia in women: factors affecting prevalence.
AB  - Coronary artery disease (CAD) is a major health care challenge, and is the
      leading cause of death amongst women. Both the delay in the clinical
      manifestations of CAD and 'atypical' symptomatology in women complicates both
      diagnosis and treatment strategies in this population. It appears that the age
      adjusted prevalence of all-cause angina (effort, unstable, etc.) appears to be
      greater in women than men, although stenotic lesions are demonstrated less
      frequently. There are a number of factors that complicates the diagnosis and
      identification of CAD in women, including more diffuse anginal symptoms, a lower
      initial detection rate of myocardial ischemia by traditional methods, lower rates
      of interventional procedures, and lastly, potential differences in the
      pathophysiology of myocardial ischemia. The lower sensitivity and specificity of
      many diagnostic techniques including ECG and various imaging technologies
      contributes significantly to these findings. The increased presence of syndrome X
      in post-menopausal women may reflect an increased likelihood of microcirculatory
      disease, where the 'gold standard' angiography fails to detect the presence of
      disease. Thus nonepicardial coronary stenotic disease may be largely undetected
      by most studies, rendering many positive ECG stress results unverifiable. The
      increased co-morbidity seen with CAD in women further complicates diagnosis and
      interventional results. Combined, these factors act to falsely lower the post
      test likelihood of disease in women, adding to the existing gender bias in the
      diagnosis and referral rates for treatment of CAD in women. The lower precision
      of disease detection in women contributes to the perception that women have less
      exertional angina than men, despite evidence to the contrary.

PMID- 11310547
TI  - Current trends in altitude training.
AB  - Recently, endurance athletes have used several novel approaches and modalities
      for altitude training including: (i) normobaric hypoxia via nitrogen dilution
      (hypoxic apartment); (ii) supplemental oxygen; (iii) hypoxic sleeping devices;
      and (iv) intermittent hypoxic exposure (IHE). A normobaric hypoxic apartment
      simulates an altitude environment equivalent to approximately 2000 to 3000m (6560
      to 9840ft). Athletes who use a hypoxic apartment typically 'live and sleep high'
      in the hypoxic apartment for 8 to 18 hours a day, but complete their training at
      sea level, or approximate sea level conditions. Several studies suggest that
      using a hypoxic apartment in this manner produces beneficial changes in serum
      erythropoietin (EPO) levels, reticulocyte count and red blood cell (RBC) mass,
      which in turn may lead to improvements in postaltitude endurance performance.
      However, other studies failed to demonstrate significant changes in
      haematological indices as a result of using a hypoxic apartment. These
      discrepancies may be caused by differences in methodology, the hypoxic stimulus
      that athletes were exposed to and/or the training status of the athletes.
      Supplemental oxygen is used to simulate either normoxic (sea level) or hyperoxic
      conditions during high-intensity workouts at altitude. This method is a
      modification of the 'high-low' strategy, since athletes live in a natural
      terrestrial altitude environment but train at 'sea level' with the aid of
      supplemental oxygen. Limited data regarding the efficacy of hyperoxic training
      suggests that high-intensity workouts at moderate altitude (1860m/6100ft) and
      endurance perfor- mance at sea level may be enhanced when supplemental oxygen
      training is utilised at altitude over a duration of several weeks. Hypoxic
      sleeping devices include the Colorado Altitude Training (CAT) Hatch (hypobaric
      chamber) and Hypoxico Tent System (normobaric hypoxic system), both of which are
      designed to allow athletes to sleep high and train low. These devices simulate
      altitudes up to approximately 4575 m/15006 ft and 4270 m/14005 ft, respectively.
      Currently, no studies have been published on the efficacy of these devices on RBC
      production, maximal oxygen uptake and/or performance in elite athletes. IHE is
      based on the assumption that brief exposures to hypoxia (1.5 to 2.0 hours) are
      sufficient to stimulate the release of EPO, and ultimately bring about an
      increase in RBC concentration. Athletes typically use IHE while at rest, or in
      conjunction with a training session. Data regarding the effect of IHE on
      haematological indices and athletic performance are minimal and inconclusive.

PMID- 11310549
TI  - Lightning injuries in sports: situations to avoid.
AB  - There is no absolute protection against lightning because of its random and
      capricious nature. However, the risk of being struck by lightning can be
      substantially reduced. There are general safety rules that apply to all athletic
      and recreational events. The athlete should have a proactive plan that can be
      instituted when storms approach. He/she should go to a safe shelter before the
      storm arrives and stay there until the danger is gone. Because the location,
      climate, terrain and playing site vary with different sporting activities, safety
      plans may have distinct elements for different recreational activities. Mountain
      climbers should know the weather patterns of their locale. The highest frequency
      of lightning strikes in the Rocky Mountains occurs between 11 am and 9 pm during
      the months of April to September. There is less chance of a hiker encountering
      lightning during the early morning hours. Many tourists are unaware of this
      pattern, which may possibly explain the finding that most lightning victims are
      visitors from other states. The bicyclist is as vulnerable as anyone in the open.
      In the event of lightning he/she should seek safe shelter and get off the bike.
      Rubber tires do not provide protection from lightning. Golfers continue to make
      the same mistakes year after year. Golfers should know to seek safe shelter
      (clubhouse or closed metal vehicle) before the storm arrives and not return
      prematurely to the golf course. They should avoid isolated trees, open fields,
      unsafe sheds and metal poles. They should separate from each other rather than
      gather together. Swimmers should get out of the pool and find a safe shelter.
      Safe areas do not include poolsides, under awnings or under trees. A nearby
      closed automobile may be the safest place until the danger is gone. Applying
      precautions when engaging in these sporting or recreational activities will help
      to minimise the risk of casualties or fatalities caused by lightning.

PMID- 11310550
TI  - Improved long-term temperature prediction by chaining of neural networks.
AB  - When an artificial neural network (ANN) is trained to predict signals p steps
      ahead, the quality of the prediction typically decreases for large values of p.
      In this paper, we compare two methods for prediction with ANNs: the classical
      recursion of one-step ahead predictors and a new kind of chain structure. When
      applying both techniques to the prediction of the temperature at the end of a
      blast furnace, we conclude that the chaining approach leads to an improved
      prediction of the temperature and avoidance of instabilities, since the chained
      networks gradually take the prediction of their predecessors in the chain as an
      extra input. It is observed that instabilities might occur in the iterative case,
      which does not happen with the chaining approach. To select relevant inputs and
      decrease the number of weights in this approach, Automatic Relevance
      Determination (ARD) for multilayer perceptrons is applied.

PMID- 11310551
TI  - Unsupervised learning and temporal context to recall complex robot trajectories.
AB  - An unsupervised neural network is proposed to learn and recall complex robot
      trajectories. Two cases are considered: (i) A single trajectory in which a
      particular arm configuration (state) may occur more than once, and (ii)
      trajectories sharing states with each other. Ambiguities occur in both cases
      during recall of such trajectories. The proposed model consists of two groups of
      synaptic weights trained by competitive and Hebbian learning laws. They are
      responsible for encoding spatial and temporal features of the input sequences,
      respectively. Three mechanisms allow the network to deal with repeated or shared
      states: local and global context units, neurons disabled from learning, and
      redundancy. The network reproduces the current and the next state of the learned
      sequences and is able to resolve ambiguities. The model was simulated over
      various sets of robot trajectories in order to evaluate learning and recall,
      trajectory sampling effects and robustness.

PMID- 11310548
TI  - Guidelines for daily carbohydrate intake: do athletes achieve them?
AB  - Official dietary guidelines for athletes are unanimous in their recommendation of
      high carbohydrate (CHO) intakes in routine or training diets. These guidelines
      have been criticised on the basis of a lack of scientific support for superior
      training adaptations and performance, and the apparent failure of successful
      athletes to achieve such dietary practices. Part of the problem rests with the
      expression of CHO intake guidelines in terms of percentage of dietary energy. It
      is preferable to provide recommendations for routine CHO intake in grams
      (relative to the body mass of the athlete) and allow flexibility for the athlete
      to meet these targets within the context of their energy needs and other dietary
      goals. CHO intake ranges of 5 to 7 g/kg/day for general training needs and 7 to
      10 g/kg/day for the increased needs of endurance athletes are suggested. The
      limitations of dietary survey techniques should be recognised when assessing the
      adequacy of the dietary practices of athletes. In particular, the errors caused
      by under-reporting or undereating during the period of the dietary survey must be
      taken into account. A review of the current dietary survey literature of athletes
      shows that a typical male athlete achieves CHO intake within the recommended
      range (on a g/kg basis). Individual athletes may need nutritional education or
      dietary counselling to fine-tune their eating habits to meet specific CHO intake
      targets. Female athletes, particularly endurance athletes, are less likely to
      achieve these CHO intake guidelines. This is due to chronic or periodic
      restriction of total energy intake in order to achieve or maintain low levels of
      body fat. With professional counselling, female athletes may be helped to find a
      balance between bodyweight control issues and fuel intake goals. Although we look
      to the top athletes as role models, it is understandable that many do not achieve
      optimal nutrition practices. The real or apparent failure of these athletes to
      achieve the daily CHO intakes recommended by sports nutritionists does not
      necessarily invalidate the benefits of meeting such guidelines. Further
      longitudinal studies of training adaptation and performance are needed to
      determine differences in the outcomes of high versus moderate CHO intakes. In the
      meantime, the recommendations of sports nutritionists are based on plentiful
      evidence that increased CHO availability enhances endurance and performance
      during single exercise sessions.

PMID- 11310552
TI  - Analogue VLSI for probabilistic networks and spike-time computation.
AB  - The history and some of the methods of analogue neural VLSI are described. The
      strengths of analogue techniques are described, along with residual problems to
      be solved. The nature of hardware-friendly and hardware-appropriate algorithms is
      reviewed and suggestions are offered as to where analogue neural VLSI's future
      lies.

PMID- 11310553
TI  - A neural network architecture for data classification.
AB  - This article aims at showing an architecture of neural networks designed for the
      classification of data distributed among a high number of classes. A significant
      gain in the global classification rate can be obtained by using our architecture.
      This latter is based on a set of several little neural networks, each one
      discriminating only two classes. The specialization of each neural network
      simplifies their structure and improves the classification. Moreover, the
      learning step automatically determines the number of hidden neurons. The
      discussion is illustrated by tests on databases from the UCI machine learning
      database repository. The experimental results show that this architecture can
      achieve a faster learning, simpler neural networks and an improved performance in
      classification.

PMID- 11310554
TI  - Best harmony, unified RPCL and automated model selection for unsupervised and
      supervised learning on Gaussian mixtures, three-layer nets and ME-RBF-SVM models.
AB  - After introducing the fundamentals of BYY system and harmony learning, which has
      been developed in past several years as a unified statistical framework for
      parameter learning, regularization and model selection, we systematically discuss
      this BYY harmony learning on systems with discrete inner-representations. First,
      we shown that one special case leads to unsupervised learning on Gaussian
      mixture. We show how harmony learning not only leads us to the EM algorithm for
      maximum likelihood (ML) learning and the corresponding extended KMEAN algorithms
      for Mahalanobis clustering with criteria for selecting the number of Gaussians or
      clusters, but also provides us two new regularization techniques and a unified
      scheme that includes the previous rival penalized competitive learning (RPCL) as
      well as its various variants and extensions that performs model selection
      automatically during parameter learning. Moreover, as a by-product, we also get a
      new approach for determining a set of 'supporting vectors' for Parzen window
      density estimation. Second, we shown that other special cases lead to three
      typical supervised learning models with several new results. On three layer net,
      we get (i) a new regularized ML learning, (ii) a new criterion for selecting the
      number of hidden units, and (iii) a family of EM-like algorithms that combines
      harmony learning with new techniques of regularization. On the original and
      alternative models of mixture-of-expert (ME) as well as radial basis function
      (RBF) nets, we get not only a new type of criteria for selecting the number of
      experts or basis functions but also a new type of the EM-like algorithms that
      combines regularization techniques and RPCL learning for parameter learning with
      either least complexity nature on the original ME model or automated model
      selection on the alternative ME model and RBF nets. Moreover, all the results for
      the alternative ME model are also applied to other two popular nonparametric
      statistical approaches, namely kernel regression and supporting vector machine.
      Particularly, not only we get an easily implemented approach for determining the
      smoothing parameter in kernel regression, but also we get an alternative approach
      for deciding the set of supporting vectors in supporting vector machine.

PMID- 11310555
TI  - A short-term temperature forecaster based on a novel radial basis functions
      neural network.
AB  - Many applications dealing with electric load forecasting in buildings require
      temperature prediction. A new method for short-term temperature forecasting based
      on a Radial Basis Functions Neural Network, initialized by a Regression Tree, is
      presented. In this method, each terminal node of the tree contributes one hidden
      unit to the RBF network. The forecaster uses the current coded hour and the
      temperature as inputs, and predicts the next hour temperature. The results
      demonstrate this predictor can be used for load forecasting.

PMID- 11310556
TI  - Neural network control systems that learn to perform appropriately.
AB  - Setting up a neural network with a learning algorithm that determines how it can
      best operate is an efficient way to formulate control systems for many
      engineering applications, and is often much more feasible than direct
      programming. This paper examines three important aspects of this approach: the
      details of the cost function that is used with the gradient descent learning
      algorithm, how the resulting system depends on the initial pre-learning
      connection weights, and how the resulting system depends on the pattern of
      learning rates chosen for the different components of the system. We explore
      these issues by explicit simulations of a toy model that is a simplified
      abstraction of part of the human oculomotor control system. This allows us to
      compare our system with that produced by human evolution and development. We can
      then go on to consider how we might improve on the human system and apply what we
      have learnt to control systems that have no human analogue.

PMID- 11310557
TI  - Modelling and prediction for chaotic fir laser attractor using rational function
      neural network.
AB  - Many real-world systems such as irregular ECG signal, volatility of currency
      exchange rate and heated fluid reaction exhibit highly complex nonlinear
      characteristic known as chaos. These chaotic systems cannot be retreated
      satisfactorily using linear system theory due to its high dimensionality and
      irregularity. This research focuses on prediction and modelling of chaotic FIR
      (Far InfraRed) laser system for which the underlying equations are not given.
      This paper proposed a method for prediction and modelling a chaotic FIR laser
      time series using rational function neural network. Three network architectures,
      TDNN (Time Delayed Neural Network), RBF (radial basis function) network and the
      RF (rational function) network, are also presented. Comparisons between these
      networks performance show the improvements introduced by the RF network in terms
      of a decrement in network complexity and better ability of predictability.

PMID- 11310558
TI  - Xenopus adenine nucleotide translocase mRNA exhibits specific and dynamic
      patterns of expression during development.
AB  - We report the isolation and characterization of the Xenopus homolog to human T1
      ANT (adenine nucleotide translocase). The 1290-nucleotide sequence contains
      initiation and termination signals, and encodes a conceptual protein of 298 amino
      acids. The sequence shares high amino acid identity with the mammalian adenine
      translocases. The transcript is present in unfertilized eggs, and it is expressed
      at higher levels during formation of the antero-posterior dorsal axis in embryos.
      Although low levels are expressed constitutively except in endodermal cells,
      adenine nucleotide translocase (ANT) expression is dynamically regulated during
      neurulation. At this stage, expression in ectoderm rapidly diminishes as the
      neural folds form, and then ANT expression increases slightly in mesoderm. At the
      culmination of neurulation, the neural tube briefly expresses ANT, and thereafter
      its expression predominates in the somitic mesoderm and also the chordoneural
      hinge. In addition, ANT expression is particularly high in the prosencephalon,
      the mesencephalon, the branchial arches, eye, and the otic vesicle. Treatment of
      embryos with retinoic acid has the effect of diminishing constitutive expression
      of ANT, but microinjection studies demonstrate that immediate and local
      repression cannot be induced in dorsal structures.

PMID- 11310559
TI  - Identification of nuclear-import and cell-cycle regulatory proteins that bind to
      prothymosin alpha.
AB  - Prothymosin alpha (ProT alpha) is a nuclear protein that is widely distributed in
      mammalian tissues, and is thought to play a role in cell proliferation. In an
      attempt to shed light on this role, affinity chromatography on ProT alpha
      Sepharose columns was used to identify proteins in subcellular extracts of
      transformed human lymphocytes (NC37 cells) that interact with ProT alpha in
      vitro, and thus may interact with ProT alpha in vivo. Immunoblotting techniques
      were used to screen the ProT alpha-binding fractions for histones and other
      proteins involved in nuclear transport and cell-cycle control. The most abundant
      ProT alpha-binding proteins were histones H2A, H2B, H3, and H4. Of the nuclear
      transport proteins, karyopherin beta1, Rch-1, Ran, and RCC1 were detected at high
      concentrations; NTF2, nucleoporin p62, and Hsp70 were detected at low
      concentrations; while tranportin, CAS, and Ran BPI were not detected. Of the cell
      cycle control proteins, PCNA, Cdk2, and cyclin A were detected at high
      concentrations; cdc2, Cdk4, and cyclin B were detected at very low
      concentrations; while cyclin D1, cyclin D3, Cip1, and Kip1 were not detected.
      These results suggest (i) that ProT alpha is transported into the nucleus by the
      karyopherin beta1-Rch-1 complex, and (ii) that ProT alpha may interact in the
      nucleus with proteins involved in DNA metabolism and cell-cycle control.

PMID- 11310560
TI  - Androgen responsiveness and intrarenal localization of transcripts coding for the
      enzymes of polyamine metabolism in the mouse.
AB  - Polyamines, spermidine (SPD), and spermine (SPM) are intracellular polycations
      required for cell growth and differentiation. Their biosynthetic precursor, the
      diamine putrescine (PUT), is produced by regulatory ornithine decarboxylase
      (ODC). Spermidine/spermine N1-acetyltransferase (SSAT) is the ODC counterpart in
      the degradation pathway which retroconverts SPM and SPD into PUT. Castration of
      male mice for 7 days resulted in a 40% decrease of the renal levels of both SSAT
      and ODC transcripts. Administration of 5-alpha-dihydrotestosterone (DHT) to
      castrated mice for the last 3 days before sacrifice caused the levels of ODC and
      SSAT mRNAs to increase by 250% and 180%, respectively. Thus activation of the
      retroconversion pathway of polyamine metabolism appears to contribute towards the
      increase in PUT production known to be caused by androgens in the mouse kidney.
      In situ hybridization histochemistry experiments showed that the SSAT transcript
      is expressed only by the epithelial cells of the straight and convoluted distal
      tubules of the nephron, while the expression of the ODC transcript is confined to
      the epithelium of the convoluted and straight portion of the proximal tubules.
      The separation of the biosynthetic from the degradation pathway along the nephron
      suggests that PUT is mostly produced in the distal tubule, where it may play a
      physiological role, independent of androgen action, in protecting tubular cells
      from the very low osmolarity to which they are exposed in this nephron segment.

PMID- 11310561
TI  - Identification of the S6 kinase activity stimulated in quiescent brine shrimp
      embryos upon entry to preemergence development as p70 ribosomal protein S6
      kinase: isolation of Artemia franciscana p70S6k cDNA.
AB  - We previously demonstrated that a protein kinase responsible for phosphorylating
      40S ribosomal subunits is activated in quiescent Artemia franciscana embryos
      within 15 min of restoration of normal tonicity and incubation at 30 degrees C.
      Here, we identify the activated S6 kinase as A. franciscana p70 ribosomal S6
      kinase (p70S6k) subsequent to the isolation of an Artemia p70S6k cDNA. The
      protein conceptually translated from cDNA has 70% similarity and 64% identity to
      both Drosophila melanogaster and human p70S6k. Southern blot analysis is
      consistent with presence of a single p70S6k gene. Two transcripts of 5.4 and 2.7
      kb were found. Abundance of both mRNAs increased dramatically around 4 h of
      preemergence development, and exhibited different steady-state level variation
      thereafter. Stimulated S6 kinase activity, partially purified by Superose 6
      chromatography, correlated best with the slowest migrating, approximately 65 kDa,
      form detected by Western analysis using a specific polyclonal antibody made to a
      peptide from the predicted p70S6k NH2-terminus. Furthermore, the A. franciscana
      p70S6k was immunoprecipitated with the same antibody, showing in parallel an S6
      kinase activity similar to peak profiles. We conclude that the stimulated S6
      kinase activity is that of an ortholog of human p70S6k that may be involved in
      the regulation of protein synthesis during preemergence development in A.
      franciscana species.

PMID- 11310562
TI  - Identification of a transcription factor, an 80-kDa protein that interacts with
      the HLH recognition motif of the rat p53 promoter.
AB  - The p53 promoter has been shown to contain a number of potential regulatory
      motifs. It was previously reported that the upstream stimulating factor (USF)
      played a central role in regulating the p53 expression. The USF binding site, E
      box, is located around 40 bp upstream of the major transcription start site. In
      this study, it was confirmed that the E-box binds to proteins by DNase I
      footprinting assay. In the electrophoretic mobility shift assay (EMSA), two
      retarded bands were detected. One band was abolished by the competition of USF
      consensus oligonucleotide, but the other band was not. This result indicated that
      a factor, other than USF, was bound to the E-box. The molecular masses of the
      binding proteins were determined by a Southwestern-blotting assay. As a result,
      46- and 80-kDa proteins were detected. The 46-kDa protein was eliminated by the
      competition of USF consensus oligonucleotide. Also, the Southwestern-blotting
      assay with 32P-labeled USF consensus oligonucleotide showed only a 46-kDa
      protein. Therefore, the 46-kDa protein was USF. These results showed that USF and
      the 80-kDa protein were bound to the E-box. In addition, it was proved by in
      vitro transcription assay that this 80-kDa protein had a basal transcriptional
      activity.

PMID- 11310563
TI  - Effects of ATP on regulation of galactosyltransferase-I activity responsible for
      synthesis of the linkage region between the core protein and glycosaminoglycan
      chains of proteoglycans.
AB  - We report that ATP enhances the activity of galactosyltransferase-I, which
      synthesizes the linkage region between glycosaminoglycan chains and the core
      proteins of proteoglycans. The enzyme activity in cell-free fractions prepared
      from cultured human skin fibroblasts was measured by high-performance liquid
      chromatographic detection of galactosyl-xylosyl-(4-methylumbelliferone) produced
      from 4-methylumbelliferyl-beta-D-xyloside used as an acceptor. ATP at 2 mM
      increased the enzyme activity by about 60% in the 110 x g supernatant of the cell
      homogenate, but not in the supernatant or precipitate fractions obtained by
      100,000 x g centrifugation. When both fractions (the 100,000 x g supernatant and
      precipitate) were mixed, the additional ATP increased the enzyme activity. This
      increase was canceled by heat treatment or trypsin digestion of the 100,000 x g
      supernatant. In addition, the 100,000 x g precipitate, which was prepared from
      the 110 x g supernatant preincubated with ATP, exhibited increased activity, and
      this increase was abolished by alkaline phosphatase treatment. These results
      suggest that a protein kinase in the 100,000 x g supernatant activates
      galactosyltransferase-I activity.

PMID- 11310564
TI  - Amine oxidase, spermine, and hyperthermia induce cytotoxicity in P-glycoprotein
      overexpressing multidrug resistant Chinese hamster ovary cells.
AB  - Multidrug resistance is a major obstacle for the successful use of chemotherapy.
      The multidrug resistance phenotype is often attributed to overexpression of P
      glycoprotein, which is an energy-dependent drug efflux pump. We investigated a
      new strategy to overcome multidrug resistance, using purified bovine serum amine
      oxidase, which generates two major toxic products from the polyamine spermine.
      The cytotoxicity of the aldehyde(s) and H2O2, produced by the enzymatic oxidation
      of micromolar concentrations of spermine, was evaluated in multidrug resistant
      Chinese hamster ovary cells CHRC5 with overexpression of P-glycoprotein, using a
      clonogenic cell survival assay. We examined the ability of hyperthermia (42
      degrees C), and inhibition of cellular detoxification systems, to sensitize
      multidrug resistant cells to spermine oxidation products. Severe depletion of
      intracellular glutathione was achieved using L-buthionine sulfoximine and
      inhibition of glutathione S-transferase by ethacrynic acid. CH(R)C5 cells showed
      no resistance to the toxic oxidation products of spermine, relative to drug
      sensitive AuxB1 cells. Exogenous catalase protected cells against cytotoxicity of
      H2O2, but spermine-derived aldehyde(s) still caused some cytotoxicity.
      Hyperthermia (42 degrees C) enhanced cytotoxicity of spermine oxidation products.
      Cytotoxic responses in CH(R)C5 cells were compared to the drug-sensitive cells,
      to determine whether there are differential responses. CH(R)C5 cells were more
      sensitive to the cytotoxic effect of spermine oxidation products under more
      extreme conditions (higher temperature, higher spermine concentration, and longer
      exposure time). Glutathione depletion or glutathione S-transferase inhibition
      also led to enhanced cytotoxicity of spermine oxidation products in CH(R)C5 and
      AuxB1 cells. Our findings suggest that hyperthermia, combined with toxic
      oxidation products generated from spermine and amine oxidase, could be useful for
      eliminating drug-sensitive and multidrug resistant cells.

PMID- 11310565
TI  - Lipid microspheres incorporated by U937 cells via their specific receptors.
AB  - Lipid microspheres (LM), currently in clinical use as drug carriers, mainly
      consist of soybean oil as a core and lecithin as a surfactant. The purpose of our
      study wass to determine whether or not LM incorporation is receptor-mediated.
      U937 cells resuspended in a serum-free medium abundantly took up unmodulated LM.
      A binding study showed that U937 cells had a single binding site for LM (410
      sites/cell at 24 degrees C; 100 sites/cell at 4 degrees C). Inhibition assays
      revealed that lecithin liposome, lysophosphatidylcholines, activated alpha2
      macroglobulin, and HDL did not affect the binding of LM to U937 cells. VLDL
      strongly, and LDL and AcLDL moderately, inhibited the binding of LM to U937
      cells. Ligand blotting analysis revealed that unmodulated LM in an apoprotein
      free buffer directly bound to a 40 kDa protein in the cell membrane fraction.
      These results suggest that LM that is not modulated by any protein is
      incorporated by specific cells via receptor-mediated processes.

PMID- 11310566
TI  - His-391 of beta-galactosidase (Escherichia coli) promotes catalyses by strong
      interactions with the transition state.
AB  - His-391 of beta-galactosidase (Escherichia coli) was substituted by Phe, Glu, and
      Lys. Homogeneous preparations of the substituted enzymes were essentially
      inactive unless very rapid purifications were performed, and the assays were done
      immediately. The inactive enzymes were tetrameric, just like wild-type beta
      galactosidase and their fluorescence spectra were identical to the fluorescence
      spectrum of wild-type enzyme. Analyses of two of the substituted enzymes that
      were very rapidly purified to homogeneity and rapidly assayed while they were
      still active (at only a few substrate concentrations so that the data could be
      rapidly obtained), showed that the kinetic values were very similar to the values
      obtained with the same enzymes that were only partially purified. This showed
      that the kinetics were not affected by the degree of purity and allowed kinetic
      analyses with partially purified enzymes so that large numbers of points could be
      used for accuracy. The data showed that His-391 is a very important residue. It
      interacts strongly with the transition state and promotes catalysis by
      stabilizing the transition state. Activation energy differences (deltadelta G(S)
      double dagger), as determined by differences in the kcat/Km values, indicated
      that substitutions for His-391 caused very large destabilizations (22.8-35.9
      kJ/mol) of the transition state. The importance of His-391 for transition state
      stabilization was confirmed by studies that showed that transition state analogs
      are very poor inhibitors of the substituted enzymes, while inhibition by
      substrate analogs was only affected in a small way by substituting for His-391.
      The poor stabilities of the transition states caused significant decreases of the
      rates of the glycolytic cleavage steps (galactosylation, k2). Degalactosylation
      (k3) was not decreased to the same extent.

PMID- 11310567
TI  - Isolation and characterization of a xylose-glucose isomerase from a new strain
      Streptomyces thermovulgaris 127, var. 7-86.
AB  - A thermostable D-xylose-glucose isomerase was isolated from the thermophilic
      strain Streptomyces thermovulgaris 127, var. 7-86, as a result of mutagenic
      treatment by gamma-irradiation of the parent strain, by precipitation and
      sequential chromatographies on DEAE-Sephadex A50, TSK-gel, FPLC-Mono Q/HR, and
      Superose 12 columns. The N-terminal amino acid sequence and amino acid analysis
      shows 73-92% homology with xylose-glucose isomerases from other sources. The
      native molecular mass, determined by gel filtration on a Superose 12 column, is
      180 kDa, and 44.6 and 45 kDa were calculated, based on amino acid analysis and
      10% SDS-PAGE, respectively. Both, the activity and stability of the enzyme were
      investigated toward pH, temperature, and denaturation with guanidine
      hydrochloride. The enzyme activity showed a clear pH optimum between pH 7.2 and
      9.0 with D-glucose and 7.4 and 8.3 with D-xylose as substrates, respectively. The
      enzyme is active up to 60-85 degrees C at pH 7.0, using D-glucose, and up to 50
      60 degrees C at pH 7.6, using D-xylose as substrates. The activation energy (Ea =
      46 kJ x mol(-1)) and the critical temperature (Tc = 60 degrees C) were determined
      by fluorescence spectroscopy. Tc is in close coincidence with the melting
      temperature of denaturation (Tm = 59 degrees C), determined by circular dichroism
      (CD) spectroscopy. The free energy of stabilization in water after denaturation
      with Gdn.HCl was calculated to be 12 k x mol(-1). The specific activity (km
      values) for D-xylose-glucose isomerase at 70 degrees C toward different
      substrates, D-xylose, D-glucose, and D-ribose, were determined to be 4.4, 55.5,
      and 13.3 mM, respectively.

PMID- 11310568
TI  - Effect of prevention and potentiation of diisopropyl phosphorofluoridate (DFP)
      induced delayed neurotoxicity on the mRNA expression of neurofilament subunits in
      hen central nervous system.
AB  - Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, which
      produces mild ataxia in 7-14 days and severe ataxia or paralysis in about 20 days
      (OPIDN) in hens. Previous studies in this laboratory have shown enhanced temporal
      expression of neurofilament (NF) subunit mRNAs in the spinal cord (SC) of DFP
      treated hens. The main objective of this investigation was to study the effect of
      DFP administration on NF subunit mRNAs expression, when OPIDN is protected or
      potentiated by pre-treatment or post-treatment, respectively, with
      phenylmethylsulfonyl fluoride (PMSF). The hens were sacrificed 1, 5, 10, and 20
      days after the last treatment. In contrast with enhanced mRNA expression of NF
      subunits reported in OPIDN, there was no alteration in the expression of NF
      subunits in the SC of PMSF-protected hens that did not develop OPIDN. PMSF post
      treatment of DFP-treated hens, which enhanced delayed neurotoxicity produced by a
      low dose of DFP, exhibited decrease in the mRNA expression of NF subunits in SC
      at all time periods (1-20 days) of observation. The expression of NF subunits was
      also studied in the degeneration-resistant tissue cerebrum of treated hens. The
      results from protected hens suggested that temporal enhanced expression of NF
      subunit mRNAs in DFP-treated hens might be contributing to the development of
      OPIDN in hens. By contrast, PMSF post-treatment seemed to potentiate OPIDN by a
      mechanism different from that followed by DFP alone to produce OPIDN.

PMID- 11310569
TI  - Preliminary FoodNet data on the incidence of foodborne illnesses--selected sites,
      United States, 2000.
AB  - Each year in the United States, an estimated 76 million persons contract
      foodborne illnesses. CDC's Emerging Infections Program Foodborne Diseases Active
      Surveillance Network (FoodNet) collects data about nine foodborne diseases in
      eight U.S. sites to quantify and monitor foodborne illnesses. This report
      describes preliminary surveillance data for 2000 and compares them with 1996-1999
      data. The data indicate the relative frequency of diagnosed infections,
      demonstrate substantial regional variation, and suggest trends in incidence.
      FoodNet provides data for monitoring foodborne illnesses and interventions
      designed to reduce them.

PMID- 11310570
TI  - Occupational and take-home lead poisoning associated with restoring chemically
      stripped furniture--California, 1998.
AB  - The Occupational Lead Poisoning Prevention Program (OLPPP) of the California
      Department of Health Services and a county health department investigated cases
      of lead poisoning in six furniture workers and their families in 1998. The
      investigation, initiated after a blood test of a worker's child revealed an
      elevated blood lead level (BLL), found that lead remaining in previously painted
      or coated stripped wood was carried from the workplace on clothes and shoes and
      was the source of the child's lead exposure and subsequent poisoning. Employers
      in industries in which workers restore or build using stripped wood should assess
      lead exposure and, when necessary, should establish a comprehensive lead safety
      program.

PMID- 11310571
TI  - Incorporating the elder caregiving role into the developmental tasks of young
      adulthood.
AB  - There is an emerging trend of young adults serving as primary caregivers to
      elderly relatives. However, existing studies have only addressed young adults'
      forecasted responses about how they might react if they were to assume the elder
      caregiver role. Research has yet to examine young adults in the actual caregiver
      role to older family members and the impact of this role on developmental tasks
      of early adulthood. In response, this study examines the impact of the elder
      caregiver role on accomplishing three major developmental tasks typical of young
      adulthood--differentiating from the family of origin, establishing intimate
      relationships, and career development. Fifty young adults providing daily care to
      elderly relatives were interviewed. The findings from both quantitative and
      qualitative data suggest that acquiring the caregiver role before age 40 has a
      definite impact on family life, intimate relationships, and career goals.

PMID- 11310572
TI  - Gambling as a social activity of older adults.
AB  - A significant number of senior citizens (aged 65+) spend their leisure time in
      gambling casinos in this country. For some older adults eager for a stimulating
      social outlet, casino gambling can become a virulent and destructive addiction.
      While prevalence studies have examined the incidence of problem gambling in other
      age groups, little attention has been paid to the impact of casino gambling on
      older adults. This study investigated the prevalence of casino gambling as a
      social activity for active senior citizens (aged 65+). Activity directors from
      residential and assisted-care facilities as well as from senior and retirement
      centers completed mailed surveys of eleven different types of social activities
      available to older adults. Results of the survey of activity directors found
      bingo the most highly frequented on-location-type social activity and casino
      gambling the most highly frequented day-trip-type social activity for 6,957
      active senior citizens represented in the activity directors' survey. On average,
      16 percent of the senior citizens were reported by the activity directors to have
      taken part in facility-sponsored trips to the casino on at least a once-a-month
      basis. In addition, the casinos themselves had offered additional gambling day
      trips to 66 percent of the facilities, which were accepted in 58 percent of the
      cases. These findings suggest the need for greater awareness of the impact casino
      gambling may have on senior citizens in this country.

PMID- 11310573
TI  - Deweyan integration: moving beyond place attachment in elderly migration theory.
AB  - The fact that aging-in-place and elderly migration are intricately linked has
      been overlooked by behavioral approaches to elderly migration. "Humanistic"
      inquiry has provided important insights into aging-in-place and elderly migration
      as well as the connection between the two. Humanistic approaches, however, do not
      encapsulate the full range of experience involved in elders' lives. To move
      beyond humanistic research and key concepts such as place attachment, the
      philosophy of John Dewey is introduced. Dewey's viewpoint is merged with the
      geographical concept of place into what is termed "place integration." This
      perspective is subsequently compared with humanistic perspectives on aging-in
      place and elderly migration decision-making. Fundamental differences such as
      temporal orientation and substantive focus are illustrated and discussed.
      Conclusions address the utility of such a perspective.

PMID- 11310574
TI  - Relationship between life satisfaction and postretirement employment among older
      women.
AB  - Although older persons' engagement in postretirement employment has been
      perceived to foster successful aging, the relationship between postretirement
      employment and elders' perceived quality of life has not been empirically tested.
      This article analyzes the effects of postretirement employment on older women's
      life satisfaction by comparing those who continued to work or (re)entered the
      labor market with those who did not engage in paid work after the receipt of
      their first Social Security benefits. The findings show that postretirement
      employment in itself does not contribute to older women's life satisfaction, but
      financial resources and especially the older women's concerns about their own
      financial situation are potent determinants of their life satisfaction. The need
      to incorporate the role of financial resources and subjective financial
      satisfaction in the theoretical framework for elders' perceived quality of life
      is discussed.

PMID- 11310575
TI  - Life satisfaction among the very old: a survey on a cognitively intact sample
      aged 90 years or above.
AB  - The purpose of the study was to measure life satisfaction and the factors
      believed to influence it. The study involved 105 very old people, ninety years
      and above, who were not cognitively impaired, living in the inner part of
      Stockholm, Sweden. In order to assess life satisfaction, the Life Satisfaction
      Index-B (LSI-B) and Life Satisfaction Index-Z (LSI-Z) were used. Information
      about life events, activities, personality and social contacts were collected in
      order to determine their relative influence on life satisfaction. Factors
      associated with life satisfaction were also investigated in a content analysis to
      find out what the elderly themselves believe gives them life satisfaction.
      Results showedthat health and an emotionally stable personality were,
      independently of other factors, the most important factors for life satisfaction
      among the very old.

PMID- 11310576
TI  - Interaction of folate and homocysteine pathway genotypes evaluated in
      susceptibility to neural tube defects (NTD) in a German population.
AB  - Neural tube defects (NTD) are likely to result from an interaction of several
      genes and environmental factors. Because periconceptional folate intake reduces
      the NTD risk in the fetus, and because mothers of children with NTD showed
      elevated plasma homocysteine levels, gene polymorphisms of the folate and
      homocysteine pathway, such as 5,10-methylenetetrahydrofolate reductase (MTHFR)
      677C-->T, MTHFR 1298A-->C and cystathionine beta-synthase (CBS) 844ins68, have
      been implicated in the etiology of NTD. Several studies have demonstrated that
      these polymorphisms may indeed be associated with NTD in some populations. In
      order to evaluate the role of these polymorphisms and their interaction in NTD,
      we genotyped 417 individuals for case-control studies and 129 families for
      transmission disequilibrium tests. We are the first to present detailed data on
      MTHFR haploid genotypes in combination with CBS 844ins68. The MTHFR risk genotype
      677CT/1298AC, known to be associated with decreased enzyme activity and increased
      homocysteine, was found significantly more often in patients than in controls (P
      = 0.02). A CBS insertion allele in addition to MTHFR 677CT/ 1298AC heterozygosity
      or MTHFR 677TT/1298AA homozygosity did not result in an increased risk for NTD.
      This is in agreement with the recently reported homocysteine-lowering effect of
      the CBS 844ins68 allele in carriers of MTHFR variants.

PMID- 11310577
TI  - Screening for deletions in interval D16-22 of the Y chromosome in azoospermic and
      oligozoospermic Japanese men.
AB  - The genetic basis of infertility remains unclear in a majority of infertile men.
      In this study, the Y chromosome long arm involving the DAZ (deleted in
      azoospermia) gene was screened in order to evaluate the occurrence of
      microdeletion in Japanese infertile men. One hundred and fifty-seven infertile
      Japanese men with azoospermia and oligozoospermia were analyzed for
      microdeletions in interval D16-22 of the Y chromosome, using polymerase chain
      reaction with sequence-tagged site markers. Sixteen sets of oligonucleotide
      primers were synthesized for the polymerase chain reaction, and Southern blot
      analysis was also performed. The men were divided into five categories on the
      basis of sperm concentration: functional azoospermia (A; n = 24), azoospermia
      caused by obstruction (AO; n = 20), oligozoospermia I (OI, sperm concentration
      less than I x 10(5)/ml; n = 33), oligozoospermia II (OII, sperm concentration
      less than 1 x 10(6)/ml; n = 30), and oligozoospermia III (OIII, sperm
      concentration less than 1 x 10(7)/ml; n = 50). Thirty fertile men with a sperm
      concentration of more than 2 x 10(7)/ml were also analyzed as controls.
      Microdeletions were identified, in 12 (7.6%) of the 157 infertile men, as
      follows: 1 man in category A, 1 in category AO, 5 in category OI, 4 in category
      OII, and 1 in category OIII. No deletion was identified in the fertile men. One
      common region around sY240 was identified in 11 of the infertile men with
      microdeletions. This locus may contain specific genes for spermatogenesis. The
      sperm concentration in the ten oligozoospermic men with microdeletions was below
      1 x 10(6)/ml. There were no correlations between the severity of spermatogenic
      defects and the extent of the microdeletions. These results suggested that genes
      in the interval D16-22 of the Y chromosome might have important roles in
      spermatogenesis.

PMID- 11310578
TI  - Mitochondrial DNA polymorphisms in Thailand.
AB  - Nucleotide sequences of the D-loop region of human mitochondrial DNA from six
      small ethnic groups of Thailand i.e., Hill tribes (Lisu and Mussur), Phuthai, Lao
      Song, Chong, and aboriginal Sakai, were analyzed. The sequences were compared
      with those of native Thai populations from two provinces, Chiang Mai and Khon
      Kaen. Based on a comparison of the 563-bp sequences in 215 Thai individuals, 137
      different sequence types were observed. Of these, 124 were unique to their
      respective populations, whereas 13 were shared between two to five populations.
      The intergenic COII/tRNALys 9-bp deletion was observed in every Thai population
      examined, except for the Sakai, with varying frequencies ranging from 18% to 40%.
      The D-loop sequences variation, and phylogenetic analysis, suggested that the 9
      bp deletion had occurred in a very ancient ancestry of Southeast Asians, although
      multiple origins of the deletion cannot be ruled out. Genetic distances, based on
      net nucleotide diversities, between populations revealed that the Sakai were
      distantly related to the other Thai populations, while the Lao Song and Chong
      were closely related to each other. Close genetic affinities were also observed
      among the Hill tribes, Phuthai, and native northeast Thai (Khon Kaen), indicating
      that they may share some degree of the common ancestral maternal lineages.

PMID- 11310579
TI  - X chromosome inactivation patterns in 45,X/46,XX mosaics.
AB  - To investigate X chromosome inactivation (XCI) patterns in 45,X/46.XX mosaics,
      genomic DNA was extracted from peripheral blood samples of 15 female subjects who
      showed different proportions of 45,X cell clones. XCI patterns were analyzed
      using two assays. The first assay was the BstXI restriction endonuclease
      detection of an X-linked phosphoglycerate kinase (PGK) gene polymorphism
      following digestion of the DNA with methylation-sensitive HpaII, or with
      methylation-insensitive AfaI as a control. The second assay was the detection of
      a CAG triplet repeat polymorphism in the X-linked androgen receptor (AR) gene
      after sodium bisulfite treatment. Of the 15 subjects, 11 were informative due to
      heterozygosity for at least one of the polymorphisms (6 were heterozygous for the
      PGK polymorphism and 9 were heterozygous for the AR polymorphism). Four of the 11
      informative subjects (36%) showed extremely skewed XCI for at least one of the
      polymorphisms, which was a much higher incidence than previously reported for
      normal females. Moreover, 3 of these 4 women had proportions of 45,X cell clones
      greater than 20%. Although our results may be due to several possible cytogenetic
      or molecular mechanisms, the most likely explanation is that cases of 45,X/46,XX
      that contain relatively high levels of 45,X cell clones probably arose due to
      structural aberrations of the X chromosome undetectable by conventional
      karyotyping.

PMID- 11310580
TI  - Human calcitonin receptor-like receptor for adrenomedullin: genomic structure,
      eight single-nucleotide polymorphisms, and haplotype analysis.
AB  - Adrenomedullin (ADM), a peptide characterized by persistent hypotensive activity,
      is thought to be involved when the control mechanism of blood pressure is
      deranged, because its plasma concentration is upregulated in hypertensive
      patients. The receptor for ADM, a molecular complex consisting of calcitonin
      receptor-like receptor (CRLR) and receptor-activity-modifying protein 2 (RAMP2),
      is activated through a unique intracellular transport mechanism. By analyzing the
      nucleotide sequences of bacterial artificial chromosome (BAC) clones, we have
      established that the gene encoding CRLR is spread over a genomic distance of
      103,145 bases; it contains 15 exons interrupted by 14 introns, including 1 that
      spans more than 60 kilobases. Exons 1-3 constitute the 5' noncoding region; exons
      4 through 15 are coding elements, of which exons 8 to 14 encode seven
      transmembrane domains. Eight novel single-nucleotide polymorphisms (SNPs) and
      their allelic frequencies in the Japanese population were found by direct
      sequencing of 32 alleles; two SNPs were in the 5' flanking region, one in exon 2,
      and the other five around intron-exon junctions. Eight haplotypes were
      constructed using these alleles in our Japanese population sample. The data
      establish a basis for investigations to detect molecular variants in the ADM
      receptor that might alter control of blood pressure and confer on individuals a
      predisposition to essential hypertension.

PMID- 11310581
TI  - Construction of 700 human/mouse A9 monochromosomal hybrids and analysis of
      imprinted genes on human chromosome 6.
AB  - As an in vitro assay system for the identification of human imprinted genes, a
      library of human/mouse A9 monochromosomal hybrids containing a single, intact bsr
      tagged human chromosome of known parental origin, derived from normal human
      fibroblasts, has been previously generated by microcell-mediated chromosome
      transfer (MMCT). To supplement this assay system, we constructed additional 700
      A9 monochromosomal hybrids, using a pSTneo or pPGKneo selection marker. To
      validate the A9 hybrids, we screened them with chromosome-specific polymorphic
      markers, and identified the hybrids containing either human chromosome 6, 7, 14,
      18, or 21 of known parental origin. Matching paternal and maternal chromosome
      pairs of A9 hybrids were identified for chromosomes 6, 7, 14, and 18. The
      paternal-specific expression of ZAC (zinc finger protein, which regulates
      apoptosis and cell cycle arrest) and HYMAI (hydatidiform mole-associated and
      imprinted transcript), and the maternal-specific methylation of a CpG island
      within an imprinted domain on human chromosome 6q24, were maintained in A9
      hybrids. For an example, we profiled the expression of expressed sequence tags
      (ESTs) and the methylation of CpG islands in the 300-kb imprinted domain around
      6q24, which may be associated with cancers and transient neonatal diabetes
      mellitus (TNDM). Thus, the 700 A9 hybrids should be useful for various aspects of
      imprinting studies.

PMID- 11310582
TI  - Glycogen storage disease type Ia: molecular study in Brazilian patients.
AB  - Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for glycogen
      storage disease type Ia (GSDIa). This disease is characterized by growth
      retardation, hepatomegaly, hypoglycemia, hyperlipidemia, and lactic acidosis. In
      this study, we report mutations in the G6Pase gene in 8 of 25 Brazilian patients
      with clinical symptoms of GSDIa. Five previously described mutations (R83C,
      Q347X, V338F, D38V, and G68R) were detected. The two most common mutations
      identified were R83C and Q347X, accounting for 8 of 14 (57.14%) mutant alleles. A
      1,176 single-nucleotide polymorphism and two intronic mutations (IVS3-58T>A and
      IVS4+10G>A) were also analyzed. We used the minigene strategy in order to verify
      the effect of these intronic mutations on the splicing mechanism. This study
      emphasizes that molecular genetic analysis is a reliable and convenient
      alternative to the assay of enzyme activity in a fresh liver biopsy specimen for
      diagnosing GSDIa.

PMID- 11310583
TI  - Four single-nucleotide polymorphisms in the human BUB1 gene.
AB  - Four single-nucleotide polymorphisms have been found in the human BUB1 gene,
      which encodes a kinase involved in the mitotic spindle checkpoint. A cytosine-to
      thymine change in exon 10, corresponding to codon 375 (c.1124C>T), causes an
      amino acid substitution of serine to phenylalanine. A guanine/cytosine
      polymorphism in exon 4 (c.279G>C) and a thymine/cytosine polymorphism in exon 12
      (c.1293T>C) do not cause amino acid substitution. The other polymorphism, of
      thymine/cytosine (IVS9-8T>C), is found at 8bp upstream of exon 10. As mutations
      of the hBUB1 gene were reported in a subset of human cancers, these polymorphisms
      could provide useful tools for the genetic study of susceptibility to various
      human cancers.

PMID- 11310584
TI  - A Chinese homozygote of familial hypercholesterolemia: identification of a novel
      C263R mutation in the LDL receptor gene.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by
      mutations in the low-density lipoprotein receptor (LDLR) gene; it is
      characterized by a high concentration of LDL, which frequently gives rise to
      tendon xanthomas and premature coronary artery disease (CAD). Individuals with
      heterozygous FH in China often exhibit a milder phenotype than those in other
      countries. The diagnosis of heterozygous FH relies on the clinical phenotype and
      this does not always permit unequivocal diagnosis of the disease. In the course
      of investigation of FH in a Chinese population sample, we found a family whose
      proband showed a markedly raised concentration of LDL cholesterol in plasma, and
      the presence of skin and tendon xanthomata. We used single-strand conformation
      polymorphism (SSCP) analysis to screen all the 18 exons and the exon-intron
      boundaries of the LDLR gene. One novel homozygous mutation, replacing T by C at
      nucleotide 850 in exon 6 was identified. This change substituted cysteine for
      arginine at codon 263 (C263R) of the LDLR. By means of mutant allele-specific
      amplification, we unequivocally diagnosed six heterozygotes with this novel
      mutation in the proband's family. forms of heterozygous FH are characterized by
      high serum LDL cholesterol levels, which are usually associated with premature
      coronary heart disease (CHD) and tendon xanthomas in early middle age, while
      homozygous FH individuals frequently suffer fatal CHD by their third decade
      (Goldstein et al. 1995). To date, more than 200 different mutations of the LDLR
      gene have been characterized worldwide (Hobbs et al. 1990; Hobbs et al. 1992;
      Varret et al. 1997). Chinese individuals with heterozygous FH are often
      recognized by virtue of their being parents of offspring with mutations in both
      alleles of the LDLR gene (Mak et al. 1998). Unlike their heterozygous parents,
      the Chinese homozygous FH patients are as severely affected, as are those
      elsewhere (Sun et al. 1994). In this article, we present an investigation of a
      Chinese family whose proband, with severe hypercholesterolemia, carried a novel
      mutation of the LDLR gene in a homozygous form, while the other six patients in
      the family, who carried this mutation in a heterozygous form, have a milder
      phenotype of FH. The main objective of our analysis was to delineate the full
      spectrum of mutations that underline FH in the Chinese population; our work
      represents a first step towards the implementation of nationwide DNA testing for
      this disease.

PMID- 11310585
TI  - Identification and allelic frequencies of novel single-nucleotide polymorphisms
      in the DUSP1 and BTG1 genes.
AB  - Defects in the activity of the PTEN gene, a tumor suppressor, are implicated in
      many types of cancer in humans. However, not all mediators of PTEN signaling
      pathways have been clarified, and, during efforts to identify such molecules, we
      previously induced expression of the DUSP1 and BTG1 genes by introducing
      exogenous PTEN into endometrial cancer cell lines. In the course of analyzing
      these two genes for mutations in ovarian carcinomas, we identified a novel single
      nucleotide polymorphism (SNP) in the DUSP1 gene, and three novel SNPs in the BTG1
      gene, and we have established their allelic frequencies in a Japanese population
      sample. These polymorphic sites will be useful for detecting losses of
      heterozygosity (LOH) in tumors and for examining latent associations between
      specific alleles and disease susceptibility.

PMID- 11310586
TI  - Multiple single-nucleotide polymorphisms (SNPs) in the Japanese population in six
      candidate genes for long QT syndrome.
AB  - We report here 20 single-nucleotide polymorphisms (SNPs), including 15 novel
      ones, in six genes that are considered to be candidates for long QT syndrome
      (LQTS): 2 SNPs in KCNB1, 3 in KCND3, 3 in KCNJ11, 7 in ABCC9, 3 in ADRB1, and 2
      in SLC18A2. We also examined their allelic frequencies in a Japanese sample
      population of LQTS-affected and nonaffected individuals. These data will be
      useful for genetic association studies designed to investigate acquired
      arrhythmias.

PMID- 11310587
TI  - Guidelines for genetic testing. The Japan Society of Human Genetics, Council
      Committee of Ethics.

PMID- 11310588
TI  - Fetal cells in transcervical samples at an early stage of gestation.
AB  - Several investigations are in progress with the aim of performing prenatal
      diagnosis of inherited disorders by noninvasive or minimally invasive techniques.
      The most important approaches are based on the detection of fetal nucleated cells
      in maternal blood, the analysis of fetal DNA present in maternal plasma, and the
      identification and isolation of fetal trophoblastic cellular elements shed into
      the uterine cavity and the endocervical canal. In this review, we discuss the
      methods that have been employed for the collection of the transcervical samples
      at an early stage of gestation and the techniques used for the identification of
      fetal cells. We also report the results of using endocervical cells for the
      detection of fetal chromosomal disorders by fluorescent in-situ hybridization and
      for performing prenatal diagnosis of fetal Rh(D) phenotypes. Recent
      investigations have also shown that--after the isolation of trophoblastic cells
      from maternal contaminants by micromanipulation--transcervical samples can be
      employed for the prenatal diagnosis of single gene defects, such as those causing
      thalassemia and sickle cell anemia. Although the present results are promising,
      further investigations are required to demonstrate the feasibility of performing
      accurate diagnosis of fetal diseases by this minimally invasive approach in all
      transcervical samples retrieved at an early stage of gestation.

PMID- 11310589
TI  - Cytokine receptor dimerization and activation: prospects for small molecule
      agonists.
AB  - Ligand-induced dimerization of cell surface receptors has emerged as a general
      mechanism for the initiation of signal transduction. A number of therapeutically
      important receptor families are believed to be activated by this process.
      Recently available structural information, particularly for the erythropoietin
      receptor, has provided insight into the mechanism of receptor activation. These
      findings have also revealed important constraints on the nature of receptor
      agonist complexes. The prospects of discovering small-molecule mimetics of such
      receptor agonists are discussed, including strategies which have led to the
      identification of a small number of peptide and non-peptide cytokine mimetics.

PMID- 11310590
TI  - Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: novel iron chelators with
      enhanced pFe3+ values.
AB  - The synthesis of a range of 2-amido-3-hydroxypyridin-4-ones as bidentate
      iron(III) chelators with potential for oral administration is described. The pKa
      values of the ligands together with the stability constants of their iron(III)
      complexes have been determined. Results indicate that the introduction of an
      amido substituent at the 2-position leads to an appreciable enhancement of the
      pFe3+ values. The ability of these novel 3-hydroxypyridin-4-ones to facilitate
      the iron excretion in bile was investigated using a 59Fe-ferritin loaded rat
      model. The optimal effect was observed with the N-methyl amido derivative 15b,
      which has an associated pFe3+ value of 21.7, more than two orders of magnitude
      higher than that of deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) 1a (pFe3+ =
      19.4). Dose response studies suggest that chelators with high pFe3+ values
      scavenge iron more effectively at lower doses when compared with simple dialkyl
      substituted hydroxypyridinones.

PMID- 11310591
TI  - Structure-activity relationships in a series of 8-substituted xanthines as A1
      adenosine receptor antagonists.
AB  - A series of 8-substituted xanthines were synthesized and their affinity in vitro
      towards A1, A2A-adenosine receptors was evaluated by radioligand receptor binding
      assays. All compounds showed a greater affinity and selectivity towards the A1
      adenosine receptor than theophylline. The compounds in which the n-proyl group is
      in 1-position of the xanthine nucleus and the pyridazinone system in 8-position
      is linked through a chain of two or four carbon atoms, showed the highest
      affinity and selectivity.

PMID- 11310592
TI  - Synthesis and pharmacological evaluation of imidazoline sites I1 and I2 selective
      ligands.
AB  - Several series of 2-aryl or heterocyclic-imidazoline compounds have been prepared
      and evaluated in vitro as imidazoline sites (I1 and I2) and alpha-adrenergic
      (alpha1 and alpha2) receptor ligands. Their pKi values indicate that linkage of
      the imidazoline moiety at the 2-position with an aromatic substituent
      dramatically decreases alpha-adrenergic affinity. I1 sites are more accessible by
      phenyl imidazolines substituted by a methyl or a methoxy group at the ortho or
      meta position. Indeed, 2-(2'-methoxyphenyl)-imidazoline (17) is one of the best
      I1 ligands ever reported (pKi = 8.53 and I1/I2 > 3388). On the other hand, I2
      selectivity increases in the presence of a methyl group in the para position. The
      original compound, 2-(3'-fluoro-4'-tolyl)-imidazoline (31) is a new potent ligand
      for the I2 sites with high selectivity (pKi = 8.53 and I2/I1 > 3388).

PMID- 11310593
TI  - Polycyclic aromatic compounds as anticancer agents: structure-activity
      relationships of chrysene and pyrene derivatives.
AB  - A large number of diamides and diamines were synthesized using 6-amino chrysene
      and 1-amino pyrene as starting materials. A structure activity study with cis
      platinum as internal control against animal and human tumor lines was carried out
      in vitro. This study indicated that the in vitro cytotoxicity toward these lines
      depends on the functionality present in the molecules. The diamino compounds were
      found to be more potent than the diamides, and these were equally active
      irrespective of the end heterocyclic group, whereas the activity of the diamides
      was strongly dependent on the terminal unit. In general, the diamides containing
      chrysene as the chromophore were more active than those with a pyrene ring. The
      size of the end heterocyclic ring, along with the nature of the spacer connecting
      the polycyclic ring to the heterocyclic ring, seemed to affect the biological
      activity in certain cell lines. Hemolysis experiments on a lead compound
      established that it had activities similar to those described for membrane
      stabilizing agents. This agent also demonstrated the capacity to produce
      differentiation in leukemia cell lines.

PMID- 11310594
TI  - 2,2-Dimethyl-2H-anthra[2,3-b]pyran-6,11-diones: a new class of cytotoxic
      compounds.
AB  - The synthesis and cytotoxic activity of some new 2,2-dimethyl-2H-anthra[2,3
      b]pyran-6,11-diones is described. Certain compounds possess interesting activity
      against murine leukemia L-1210 cells. Relationships between the biological
      activity and the pyrano-ring conformations are discussed.

PMID- 11310595
TI  - Imidazoline-modified benzylimidazolines as h5-HT(1D/1B) serotonergic ligands.
AB  - Sumatriptan, a h5-HT1D and h5-HT1B receptor agonist used clinically as a migraine
      abortive, produces certain side effects thought to result from its affinity for
      h5-HT1B receptors. The present investigation extends our work with
      benzylimidazolines as novel non-tryptamine h5-HT(1D/1B) ligands. The effect of N
      methylation, N-benzylation, ring-aromatization, and variation of the imidazoline
      ring on affinity both at h5-HT1D and h5-HT1B receptors was examined. Several
      compounds were identified with good affinity and enhanced (i.e., > 100-fold) h5
      HT1D versus hS-HT1B selectivity.

PMID- 11310596
TI  - Ring-deactivated hydroxymethylpyrroles as inhibitors of alpha-chymotrypsin.
AB  - N-Acyl and N-sulfonylhydroxymetyhylpyrroles have been synthesised and shown to
      inhibit alpha-chymotrypsin. A hydrophobic group in the N-substituent has been
      shown to be required for activity.

PMID- 11310597
TI  - New polycyclic pyrimidine derivatives with antiplatelet in vitro activity:
      synthesis and pharmacological screening.
AB  - The preparation and the pharmacological screening of novel anti
      aggregatory/antiphlogistic polycyclic pyrimidine derivatives are described. The
      compounds were developed starting from bioactive 2-aminobenzopyranopyrimidine
      derivatives in order to assess the importance of the benzopyrano[4,3-d]pyrimidine
      structure and the role of an amino basic moiety in position 2. Antiplatelet
      activity was assessed in vitro against ADP and arachidonic acid-induced
      aggregation in guinea-pig plasma. Anti-inflammatory/analgesic/antipyretic
      activities were studied in rat paw oedema, mouse writhing test and E. coli
      induced rat fever. Ulcerogenic and gastroprotective effects were also
      investigated in vivo on rat gastric mucosa. Among the tested compounds, the 5
      substituted benzopyranopyrimidine derivatives 3d and 4d proved to be the most
      active antiplatelet agents as potent as acetylsalicylic acid against arachidonic
      acid-stimulated aggregation. Furthermore the 2-methylthio derivative 4d was
      endowed with greater efficacy against ADP aggregation suggesting that additional
      non-TXA2 dependent mechanisms are involved in its biological activity. Orally
      administered at 100 mg kg(-1) in rats this latter compound displayed
      antiphlogistic acitivity comparable to indomethacin (10 mg kg(-1)) coupled with
      an unusual gastroprotective effect on ethanol-induced ulcers. In conclusion,
      these findings indicate that the 5-pyrrolidino-2-methylthiobenzopyrano[4,3
      d]pyrimidine 4d fulfils the chemical requirements to exhibit antiplatelet
      activity associated with gastroprotective effect.

PMID- 11310598
TI  - 6-Acylamino-2-1[(ethylsulfonyl)oxy]-1H-isoindole-1,3-diones mechanism-based
      inhibitors of human leukocyte elastase and cathepsin G: effect of chirality in
      the 6-acylamino substituent on inhibitory potency and selectivity.
AB  - Inhibition of human leukocyte elastase(HLE) by a series of 6-acylamino-2
      [(ethylsulfonyl)oxy)]-1H-isoindole-1,3-diones was determined and compared to
      their inhibition of ChT, PPE, and Cat G. The best inhibitor of the series was 6
      ((1'S)-camphanyl)amino-2-[(ethylsulfonyl) oxy]-1H-isoindole-1,3-dione 5b, with a
      k(obs)/[I] = 11,000 M(-1) s(-1). This study revealed that HLE shows a preference
      for the S stereochemistry and tolerates hydrophobic substituents in the Sn'
      binding sites. Molecular modeling of non-covalent HLE-inhibitor complexes was
      used as a tool to investigate our binding model. Buffer stability assays reveal
      that these compounds are susceptible to hydrolysis at physiological pH.

PMID- 11310599
TI  - The crystal structure of the complex of non-peptidic inhibitor of human
      neutrophil elastase ONO-6818 and porcine pancreatic elastase.
AB  - The crystal structure of a new inhibitor of human neutrophil elastase (HNE), N-[2
      [5-(tert-butyl)-1,3,4-oxadiazol-2-yl]-(IRS)-1-(methylethyl)-2-oxoethyl]-2-(5
      amino-6-oxo-2-phenyl-6H-pyrimidin-1-ly)acetamide (ONO-6818, 1) complexed to
      porcine pancreatic elastase (PPE) has been determined at 1.86 A resolution.
      Analytical results provided evidence of a 1:1 complex in which the electrophilic
      ketone of 1 covalently bound to O gamma of Ser195 at the active site of PPE. The
      role of the unique electron-withdrawing ketone of 1 has been elucidated.

PMID- 11310600
TI  - Expanding the recognition of the minor groove of DNA by incorporation of beta
      alanine in hairpin polyamides.
AB  - In order to expand the recognition code by hairpin polyamides to include DNA
      sequences of the type 5'-CWWC-3' two polyamides, PyPyPyPy-(R)(H2N)gamma-ImPyPyIm
      beta-Dp (1) and PyPyPyPy-(R)(H2N)gamma-ImPy-beta-Im-beta-Dp (2) were synthesized
      which have in common an Py/Im pair in the terminal position for targeting C x G
      but differ with respect to internal placement of a beta-alanine residue. The
      equilibrium association constants (Ka) were determined at four DNA sites which
      differ at a single common position, 5'-TNTACA-3' (N = T, A, G, C). Quantitative
      DNase I footprint titration experiments reveal that the eight-ring hairpin
      PyPyPyPy-(R)(H2N)gamma-ImPyPyIm-beta-Dp (1) binds the four binding sites with
      similar affinities, Ka = 1.3-1.9 x 10(10) M(-1) indicating that there is no
      preference for the position N. In contrast, a redesigned polyamide PyPyPyPy
      (R)(H2N)gamma-ImPy-beta-Im-beta-Dp (2) that places an internal flexible aliphatic
      beta-alanine to the 5'-side of a key imidazole group bound the match site 5'
      TCTACA-3' with high affinity and good sequence discrimination (Ka(match) = 4.9 x
      10(10) M(-1) and the single base pair mismatch sites with 5- to 25-fold lower
      affinity). These results expand the repertoire of sequences targetable by
      hairpins and emphasize the importance of beta-alanine as a key element for minor
      groove recognition.

PMID- 11310601
TI  - Synthesis, electrochemistry, and molluscicidal activity of nitroaromatic
      compounds: effects of substituents and the role of redox potential.
AB  - Abstract-Molluscicidal bioassays and electrochemical studies (measurement of
      first wave reduction potential, Epcl) were performed on several synthetic
      nitroaromatics, in relation to possible correlation between biological activity,
      redox potential and structural effects. Five of them presented a significant
      molluscicidal activity on Biomphalaria glabrata (LD50 < 20 ppm). The Epc1 values
      ranged from -0.532 to -0.857 V versus Ag/AgCl (0.1 M) (-0.260 to -0.585 V versus
      NHE), all of them, in the favorable range for reduction in vivo. Data comparison
      between Epc1 and molluscicidal activity indicates that the presence of the
      electroactive nitro group is important for the biological activity. Correlation
      with redox potential, however, was not evident. Structural effects seem to be the
      most important parameter. Higher activity is noticeable for phenols, including
      the para-nitro azo or hydrazo-containing compounds. No activity was observed for
      compounds having the benzylic substituent in meta position to the nitro group.
      These results suggest that activity undoubtedly involves more than reduction
      characteristics and that the possible formation of electrophilic species, after
      nitro reduction, can play an important role in molluscicidal activity against B.
      glabrata.

PMID- 11310602
TI  - Synthesis of [18F]-labeled EF3 [2-(2-nitroimidazol-1-yl)-N-(3,3,3
      trifluoropropyl)-acetamide], a marker for PET detection of hypoxia.
AB  - [18F]-2-(2-Nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)-acetamide ([18F]-EF3)
      has been prepared, in 65% chemical yield and 5% radiochemical yield, by coupling
      2,3,5,6-tetrafluorophenyl 2-(2-nitroimidazol-1-yl) acetate 1 with [18F]-3,3,3
      trifluoropropylamine 7. This original radiolabelled key-synthon was obtained in
      40% overall chemical yield by oxidative [18F]-fluorodesulfurization of ethyl N
      phthalimido-3-aminopropane dithioate 4, followed by deprotection with hydrazine
      of the resulting [18F]-N-phthalimido-3,3,3-trifluoropropylamine 5. All the
      process was performed within 90 min, from the [18F]-HF production in the
      cyclotron to the purification of the final target.

PMID- 11310603
TI  - Synthesis of high-specific-radioactivity 4- and 6-[18F]fluorometaraminol-PET
      tracers for the adrenergic nervous system of the heart.
AB  - Fluorine-18- (t(1/2) 109.8 min) and carbon-11 (t(1/2) 20.4 min)-labeled
      norepinephrine analogues have been found previously to be useful positron
      emission-tomography (PET) radioligands to map adrenergic nerve terminals of the
      heart. Metaraminol ((1R,2S)-2-amino-1-(3-hydroxyphenyl)-1-propanol) is a
      metabolically stable structural analogue of norepinephrine and possesses high
      affinity towards the norepinephrine transporter and the vesicular monoamine
      transporter. This paper presents the radiosynthesis of new positron-emission
      tomography halogeno analogues of metaraminol labeled with high specific
      radioactivity. Firstly, fluorine-18-labeled 4-fluorometaraminol (4-[18F]FMR or
      (1R,2S)-2-amino-1-(4-[18F]fluoro-3-hydroxyphenyl)-1-propanol) and its three other
      stereoisomers were prepared based on the following key steps: (a) condensation of
      the corresponding no-carrier-added labeled fluorobenzaldehyde with nitroethane,
      and (b) HPLC (C18 and chiral) resolution of the diastereomeric product mixture
      into the four individual enantiomers. Secondly, the corresponding 6-fluoro
      analogues, fluorine-18-labeled 6-fluorometaraminol (6-[18F]FMR or (1R,2S)-2-amino
      1-(2-[18F]fluoro-5-hydroxyphenyl)-1-propanol) and its three other enantiomers,
      were prepared in an analogous way. Typically, 0.48-0.55 GBq of 4-[18F]FMR and
      0.14-0.15 GBq of 6-[18F]FMR could be obtained after 120-160 min total synthesis
      time, with a specific radioactivity of 56-106 GBq/micromol. Furthermore, the
      synthesis of racemic 4-fluorometaraminol and 6-fluorometaraminol as reference
      compounds was performed. as well as independent chiral syntheses of the optically
      active (1R,2S) enantiomers. For the chiral syntheses, the key step was an
      electrophilic fluorination with acetyl hypofluorite of (1R,2S)-configurated
      organometallic derivatives of metaraminol. Tissue distribution studies in rats
      suggested that both 4-[18F]FMR and 6-[18F]FMR display similar affinity towards
      the presynaptic adrenergic nerve terminal in the heart. From a practical point of
      view, 4-[18F]FMR appeared to be the more attractive candidate for future PET
      investigations, due to higher radiochemical yields.

PMID- 11310604
TI  - Short and efficient syntheses of analogues of WAY-100635: new and potent 5-HT1A
      receptor antagonists.
AB  - Simple syntheses of four new and potent analogues of the 5-HT1A receptor ligand,
      WAY-100635 are described, namely the 6-(pyridinyl)-bromo-, the 6-(pyridinyl)
      fluoro-, the pyrimidine- and the 5-(pyridinyl)-bromo-analogues. The first three
      analogues were obtained by aromatic nucleophilic substitution of the 2,6
      dihalogenopyridine (activated or not as an N-oxide) or of the 2-chloropyrimidine
      with the corresponding amine nucleophile as a key step. The fourth analogue, the
      5-(pyridinyl)-bromo-analogue, was synthesized from the 2-amino-5-bromopyridine
      via a progressive elongation of the skeleton. The four compounds described are
      all full antagonists and show good in vitro binding affinities (Ki).

PMID- 11310605
TI  - Carbonic anhydrase inhibitors: sulfonamides as antitumor agents?
AB  - Novel sulfonamide inhibitors of the zinc enzyme carbonic anhydrase (CA, EC
      4.2.1.1) were prepared by reaction of aromatic or heterocyclic sulfonamides
      containing amino, imino, or hydrazino moieties with N,N-dialkyldithiocarbamates
      in the presence of oxidizing agents (sodium hypochlorite or iodine). The N,N
      dialkylthiocarbamylsulfenamido-sulfonamides synthesized in this way behaved as
      strong inhibitors of human CA I and CA II (hCA I and hCA II) and bovine CA IV
      (bCA IV). For the most active compounds, inhibition constants ranged from 10(-8)
      to 10(-9) M (for isozymes II and IV). Three of the derivatives belonging to this
      new class of CA inhibitors were also tested as inhibitors of tumor cell growth in
      vitro. These sulfonamides showed potent inhibition of growth against several
      leukemia, non-small cell lung, ovarian, melanoma, colon, CNS, renal, prostate and
      breast cancer cell lines. With several cell lines. GI50 values of 10-75 nM were
      observed. The mechanism of antitumor action with the new sulfonamides reported
      here remains obscure, but may involve inhibition of CA isozymes which predominate
      in tumor cell membranes (CA IX and CA XII), perhaps causing acidification of the
      intercellular milieu, or inhibition of intracellular isozymes which provide
      bicarbonate for the synthesis of nucleotides and other essential cell components
      (CA II and CA V). Optimization of these derivatives from the SAR point of view,
      might lead to the development of effective novel types of anticancer agents.

PMID- 11310606
TI  - Synthesis and anti-inflammatory activities of N4,N5-disubstituted-3-methyl- H
      pyrazolo[3,4-c]pyridazines.
AB  - The synthesis and anti-inflammatory activity of 4,5-dihydroxy-3-methyl-1H
      pyrazolo[3,4-c]pyridazine (4), 4,5-dichloro-3-methyl-1H-pyrazolo[3,4-c]pyridazine
      (5), 4,-benzoyloxy-3-methyl-1-benzoyl-1H-pyrazolo[3,4-c]pyridazin-5yl benzoate
      (6), 3-methyl-N4,N5-bis(4-methylphenyl)-1H-pyrazolo[3,4-c]pyridazine-4,5-diamine
      (7), 4[[5-(4-carboxyanilino)-3-methyl-1H-pyrazolo[3,4-c]pyridazin
      4yl]amino]benzoic acid (8), N-[5-(benzoylamino)-3-methyl-1H-pyrazolo[3,4
      c]pyridazin-4-yl]benzamide (9) and 3-methyl-N4,N5-bis[4-(1H-benzimidazol
      2yl)phenyl]-1H-pyrazolo[3,4-c]pyridazine-4,5-diamine (10) are being reported.

PMID- 11310607
TI  - Anti-leukemia selectivity in actinomycin analogues.
AB  - An excellent anti-leukemia activity has been found in a group of actinomycin D
      analogues derivatized at the 2,2'- or 5,5'-position of the depsipeptides. On the
      basis of the water solubilities, the DNA binding affinities, the RNA synthesis
      inhibitory activities, the anticancer activities of actinomycin D (AMD), and the
      crystal structures of DNA-AMD complexes, it becomes clear that AMD is extremely
      well designed as an effective poison produced by micro-organisms. The anticancer
      activity of AMD is mainly due to its selective inhibition of RNA synthesis. We
      have hypothesized that a modification on the AMD structure at a site not involved
      in DNA interaction can either increase or decrease the diffusion rate of the
      analogue into certain cancer cells. Since the i-propyl groups of the D-valine
      residues at the 2,2'-positions and N-methyl-L-valine residues at the 5,5'
      positions in the depsipeptides do not participate in interaction with DNA, these
      amino acid residues were replaced with other D-amino acid residues and N-methyl-L
      amino acid residues, respectively. The cancer screen tests have indicated that
      AMD analogues 2,2'-D-PheAMD, 2,2'-D-OmeAMD, 5,5'-L-TyrAMD, 5,5'-D-ValAMD, 5,5'-D
      TyrAMD, 5,5'-D-PheAMD, and 5,5'-D-OmeAMD, inhibit selectively the growth of
      leukemia cell lines at about 100- to 500-fold lower drug concentrations than
      those required to inhibit other cancer cell lines.

PMID- 11310608
TI  - Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of
      new tacrine-like analogues.
AB  - The synthesis and preliminary results for acetylcholinesterase and
      butyrylcholinesterase inhibition activity of a series of pyrano[2,3-b]quinolines
      (2, 3) and benzonaphthyridines (5, 6) derivatives are described. These molecules
      are tacrine-like analogues which have been prepared from readily available
      polyfunctionalized ethyl [6-amino-5-cyano-4H-pyrans and 6-amino-5-cyanopyridines]
      3-carboxylates via Friedlander condensation with selected ketones. These
      compounds showed moderate acetylcholinesterase inhibition activity, the more
      potent (2e, 5b) being 6 times less active than tacrine. The butyrylcholinesterase
      activity of some of these molecules is also discussed.

PMID- 11310609
TI  - Iminosugars: potential inhibitors of liver glycogen phosphorylase.
AB  - The first synthesis of the single isomers (3R,4R,5R); (3S,4S,5S): (3R,4R,5S) and
      (3S,4S,5R) of 5-hydroxymethyl-piperidine-3,4-diol from Arecolin is reported,
      including the synthesis of a series of N-substituted derivatives of the
      (3R,4R,5R)-isomer (Isofagomine). The inhibitory effect of these isomers as well
      as of a series of N-substituted derivatives of the (3R,4R,5R)-isomer and selected
      hydroxypiperidine analogues on liver glycogen phosphorylase (GP) showed that the
      (3R,4R,5R) configuration was essential for obtaining an inhibitory effect at
      submicromolar concentration. The results also showed that all three hydroxy
      groups should be present and could not be substituted, nor were extra OH groups
      allowed if sub-micromolar inhibition should be obtained. Some inhibitory effect
      was retained for N-substituted derivatives of Isofagomine; however, N
      substitution always resulted in a loss of activity compared to the parent
      compound, IC50 values ranging from 1 to 100 microM were obtained for simple
      alkyl, arylalkyl and benzoylmethyl substituents. Furthermore, we found that it
      was not enough to assure inhibitory effect to have the (R,R,R) configuration.
      Fagomine, the (2R,3R,4R)-2-hydroxymethylpiperidine-3,4-diol analogue, showed an
      IC50 value of 200 microM compared to 0.7 microM for Isofagomine. In addition,
      Isofagomine was able to prevent basal and glucagon stimulated glycogen
      degradation in cultured hepatocytes with IC50 values of 2-3 microM.

PMID- 11310610
TI  - Synthesis of indomethacin analogues for evaluation as modulators of MRP activity.
AB  - Synthesis of a range of indomethacin analogues, required for investigation in
      combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is
      described.

PMID- 11310611
TI  - Synthesis, receptor binding affinities and conformational properties of cyclic
      methylenedithioether analogues of angiotensin II.
AB  - Cyclic 12-, 13- and 14-membered ring angiotensin II analogues related to
      disulfides but encompassing methylene-dithioether bridges have been prepared. The
      affinity data from these derivatives were compared to those from the disulfides.
      The methylenedithioether analogues displayed good binding affinities to rat liver
      AT1 receptors although in most cases somewhat lower than their disulfide
      counterparts. One of the methylenedithioethers with a 13-membered ring system
      demonstrated the highest binding affinity among the thioethers. Theoretical
      conformational analysis of model compounds of the two series were performed
      suggesting a similarity between the disulfide and the corresponding
      methylenedithioether analogues and also between the ring size homologues. This
      analysis also suggested that some of the model compounds were prone to adopt
      inverse gamma-turn conformations, which was further supported by use of NMR
      spectroscopy of the 12-membered ring analogue in the series. The easily executed
      methylenedithioether cyclization should constitute a valuable complement to the
      common disulfide methodology for fine-tuning and for probing the bioactive
      conformation of peptides.

PMID- 11310612
TI  - Selective inhibition of Trypanosoma brucei GAPDH by 1,3-bisphospho-D-glyceric
      acid (1,3-diPG) analogues.
AB  - Various phosphono-phosphates and diphosphonates were synthesized as 1,3
      diphosphoglycerate (1,3-diPG) analogues by using a beta-ketophosphonate, an alpha
      fluoro,beta-ketophosphonate or a beta-ketophosphoramidate to mimic the unstable
      carboxyphosphate part of the natural substrate. The inhibitory effect of these
      analogues on glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from Trypanosoma
      brucei (Tb) and rabbit muscle were measured with respect to both substrates,
      glyceraldehyde-3-phosphate (GAP) and 1,3-diPG. Interestingly, all 1,5
      diphosphono,2-oxopentanes without substitution at the C-3 position selectively
      inhibit the Tb GAPDH with respect to 1,3-diPG and are without effect on Rm GAPDH.
      All 1-phospho,3-oxo,4-phosphonobutanes show themselves to be non-selective
      inhibitors either with regard to substrates or organisms, but they will be of a
      great interest as 1,3-diPG stable models for structural studies of co-crystals
      with GAPDHs.

PMID- 11310613
TI  - Discovery of a novel lead structure for anti-malarials.
AB  - From a library of 61 compounds available from former studies 2,5-bis
      acylaminobenzophenone 7p was identified as a lead structure for a novel class of
      anti-malaria agents active against multi-resistant Plasmodium falciparum strain
      Dd2. Some structural modifications of this initial lead demonstrated the
      potential for further improvement of the anti-plasmodial activity of this novel
      class of anti-malarials.

PMID- 11310614
TI  - Biotransformation of a 4(20),11(12)-taxadiene derivative.
AB  - A 4(20),11(12)-taxadiene derivative was converted to hydroxylated derivatives by
      Cunninghamella elegans AS3.2033 and Cunninghamella elegans var chibaensis ATCC
      20230. Both microorganisms led to C-1 hydroxylations and conversion to a C-15
      hydroxylated abeo-taxane. Additional products from the two fungi differed: a C-14
      oxidation and a trans-cis isomerization of the cinnamoyl for one and an
      unprecedented hydroxylation at C-17 for the other.

PMID- 11310615
TI  - Identification and structural determination of a potent P-selectin inhibitor.
AB  - Small quantities of a potent P-selectin inhibitor, 2 (IC50 = 0.2 microM), were
      isolated and an initial structure proposed based on 1D proton NMR. A
      reterosynthetic analysis of the proposed structure led us to a total synthesis of
      2. NMR studies using the 2-D homo-TOCSY and NOESY and 2-D hetero-HMQC helped to
      confirm the structure of 2.

PMID- 11310616
TI  - Effect of chemical modifications of cytosine and guanine in a CpG-motif of
      oligonucleotides: structure-immunostimulatory activity relationships.
AB  - Oligodeoxynucleotides containing unmethylated CpG-motifs stimulate the innate
      immune system, including inducing B-cell proliferation and cytokine production.
      However, the mechanism of immunostimulation by CpG-oligonucleotides and the
      precise structural requirements and specific functional groups of cytosine and
      guanine necessary for recognition of and interaction with protein/receptor
      factors that are responsible for immune stimulation have not been elucidated. We
      sought to understand the critical role of each functional group of the cytosine
      and guanine moieties in a CpG-motif in inducing immunostimulatory activity. To
      this end, we examined structure-immunostimulatory activity relationships of
      phosphorothioate oligodeoxynucleotides (PS-oligos) containing YpG- and CpR-motifs
      (Y and R stand for pyrimidine and purine analogues, respectively). The PS-oligos
      containing a YpG-motif in which the natural deoxycytidine was replaced with deoxy
      5-hydroxycytidine or deoxy-N4-ethylcytidine showed immunostimulatory activity.
      Substitution of deoxycytidine with a deoxy-5-methylisocytidine, deoxyuridine, or
      deoxy-P-base-nucleoside in the YpG-motif completely abolished the
      immunostimulatory activity, similar to the results observed with deoxy-5
      methylcytidine. In the case of PS-oligos containing a CpR-motif, 7-deazaguanine
      substitution for natural guanine showed immunostimulatory activity similar to
      that of a parent PS-oligo. These studies suggest that the 2-keto, 3-imino and 4
      amino groups of cytosine, and the 1-imino, 2-amino and 6-keto groups of guanine
      in a CpG-motif are important for the immunostimulatory activity of CpG-PS-oligos.
      The absence of N7 on guanine of the CpG-motif does not affect immunostimulatory
      activity significantly. These studies suggest that it is possible to develop YpG-
      and CpR-motifs as an alternative to CpG-motifs in PS-oligos for immunostimulatory
      studies.

PMID- 11310617
TI  - Focal dementia syndromes: in search of the gold standard.

PMID- 11310618
TI  - N-acetyl aspartate--a neuronal marker?

PMID- 11310619
TI  - Primary progressive aphasia.
AB  - Primary progressive aphasia (PPA) is a focal dementia characterized by an
      isolated and gradual dissolution of language function. The disease starts with
      word-finding disturbances (anomia) and frequently proceeds to impair the
      grammatical structure (syntax) and comprehension (semantics) of language. The
      speech output in PPA can be fluent or nonfluent. Memory, visual processing, and
      personality remain relatively well-preserved until the advanced stages and help
      to distiguish PPA from frontal lobe dementia and the typical forms of Alzheimer's
      disease. The term "semantic dementia" was originally introduced to designate a
      different group of patients with a combination of verbal and visual processing
      deficits. In practice, however, this diagnosis is also being used in a variant
      sense to denote a subtype of PPA with fluent speech and impaired comprehension,
      even in the absence of visual processing deficits. Insofar as the diagnosis of
      semantic dementia can have these two different meanings, it is important to
      specify whether it is being used in the original sense or to denote a subtype of
      PPA. Structural and physiological neuroimaging confirms the selective
      predilection of PPA for the left hemisphere, especially for its language-related
      cortices. A few patients with PPA display the neuropathological markers of
      Alzheimer's disease, but in an unusual distribution. The majority of the
      autopsies in PPA have shown either Pick's disease or lobar atrophy without
      distinctive histopathology. The suggestion has been made that PPA and frontal
      lobe dementia constitute phenotypical variations of a unitary disease process
      within the "Pick-lobar atrophy" spectrum. Recent advances in chromosome 17-linked
      dementias justify a rigorous search for tau polymorphisms and tauopathy in
      sporadic PPA. An informed approach to this syndrome will increase the
      effectiveness with which clinicians can address the unique challenges associated
      with the diagnosis and care of PPA.

PMID- 11310620
TI  - Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease.
AB  - Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to
      quantify the global and temporal lobe atrophy in semantic dementia and
      Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia
      patients, Alzheimer's disease patients, and control subjects. The temporal lobe
      structures measured were the amygdala, hippocampus, entorhinal cortex,
      parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior
      temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ
      significantly on global atrophy measures. In semantic dementia, there was
      asymmetrical temporal lobe atrophy, with greater left-sided damage. There was an
      anteroposterior gradient in the distribution of temporal lobe atrophy, with more
      marked atrophy anteriorly. All left anterior temporal lobe structures were
      affected in semantic dementia, with the entorhinal cortex, amygdala, middle and
      inferior temporal gyri, and fusiform gyrus the most severely damaged.
      Asymmetrical, predominantly anterior hippocampal atrophy was also present. In
      Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex,
      hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the
      distribution of temporal lobe or hippocampal atrophy. These data demonstrate that
      there is a marked difference in the distribution of temporal lobe atrophy in
      semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in
      semantic dementia suggests that semantic memory is subserved by anterior temporal
      lobe structures, within which the middle and inferior temporal gyri may play a
      key role.

PMID- 11310621
TI  - A novel autosomal dominant distal myopathy with early respiratory failure:
      clinico-pathologic characteristics and exclusion of linkage to candidate genetic
      loci.
AB  - We describe a novel autosomal dominant myopathy presenting in mid-adult life with
      tibialis anterior weakness. We carried out a detailed clinical assessment of 24
      individuals spanning three generations, documenting pathologic features of the
      muscles in 7 of the 11 affected individuals, including an autopsy study on one
      case. The second generation of affected individuals presented at an earlier age,
      and the disease progressed more rapidly than in the first generation. Lung
      function tests revealed progressive global respiratory muscle weakness detectable
      from the time of presentation, with preferential diaphragmatic involvement in
      some cases. Hip girdle and shoulder girdle weakness appeared later in the disease
      course. We observed a striking correlation between the clinical and pathological
      features. Clinically unaffected muscles had minimal pathologic change. Fiber
      splitting, eosinophilic inclusions, and vacuoles with basophilic rims were seen
      in moderately affected muscles, and fat and fibrous connective tissue replaced
      muscle fibers in the severely involved muscles. The inclusions were Congophilic
      and reacted with antibodies to desmin, beta-amyloid, and phosphorylated tau
      protein. The disease was not linked to any of the known loci associated with
      distal myopathies, confirming that the disorder in this family is both
      genetically and phenotypically distinct.

PMID- 11310622
TI  - Alpha-adrenergic supersensitivity of the sudomotor nerve in complex regional pain
      syndrome.
AB  - alpha-Adrenoreceptor supersensitivity in many tissues has been described in
      patients with complex regional pain syndrome type I (CRPS I). Because excessive
      sweating of the affected limb is an important feature of CRPS I, we investigated
      whether this supersensitivity also occurs in the sudomotor system. We compared
      the sweat response to iontophoresis of an alpha-adrenergic agent (phenylephrine)
      in 4 patients with acute CRPS I and 3 patients with resolved CRPS I with that in
      9 control subjects using the methodology of the quantitative sudomotor axon
      reflex test (QSART). A significantly higher sweat response was observed in the
      affected limb of patients with acute CRPS I compared to their unaffected limb (p
      = 0.03), to control subjects (p > 0.018), and to the affected or unaffected limbs
      of patients with resolved CRPS I (p = 0.02), whose sweat response was not
      significantly different from that of control subjects. We conclude that the
      abnormal response in patients with acute CRPS I is most likely mediated by an
      axon reflex and that alpha-adrenoreceptor supersensitivity occurs in the
      presynaptic portion of the postganglionic sudomotor axon. This supersensitivity
      is reversed when CRPS I resolves.

PMID- 11310623
TI  - Stroke magnetic resonance imaging within 6 hours after onset of hyperacute
      cerebral ischemia.
AB  - We studied the diagnostic and prognostic value of diffusion- and perfusion
      weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and
      follow-up monitoring of patients with stroke that had ensued less than 6 hours
      previously. Further, we examined the role of vessel patency or occlusion and
      subsequent recanalization or persistent occlusion for further clinical and
      morphological stroke progression so as to define categories of patients and
      facilitate treatment decisions. Fifty-one patients underwent stroke magnetic
      resonance imaging (DWI, PWI, magnetic resonance angiography, and T2-weighted
      imaging) within 3.3 +/- 1.29 hours, and, of those, 41 underwent follow-up
      magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed
      clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian
      Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and
      90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a
      proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients
      exhibited recanalization on day 2. Vessel occlusion was associated with a PWI-DWI
      mismatch on the initial magnetic resonance imaging, vessel patency with a PWI-DWI
      match (p < 0.0001). Outcome scores and lesion volumes differed significantly
      between patients experiencing recanalization and those who did not (all p <
      0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical
      scores and only modestly with outcome scores. We have concluded on the basis of
      this study that early recanalization saves tissue at risk of ischemic infarction
      and results in significantly smaller infarcts and a significantly better clinical
      outcome. Patients with proximal vessel occlusions have a larger amount of tissue
      at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization
      seems to be of utmost importance for these patients.

PMID- 11310624
TI  - Electrically active axons degenerate when exposed to nitric oxide.
AB  - Axonal degeneration is a major cause of permanent deficit in inflammatory
      neurological diseases such as multiple sclerosis. Axons undergo degeneration
      specifically at the site of the inflammatory lesions, suggesting that locally
      produced inflammatory factors mediate the phenomenon. One such factor is nitric
      oxide (NO), which we have previously reported can cause reversible conduction
      block in axons. Here we confirm these observations and extend them to show that
      axons exhibit the early stages of wallerian degeneration if they are conducting
      impulses at physiological frequencies while they are exposed to the low
      micromolar concentrations of NO that are likely to occur at sites of
      inflammation. Rat dorsal roots were concurrently exposed in vivo to both NO and
      sustained impulse activity at 1, 50, or 100 Hz. Although our in vivo observations
      necessarily focused on the more acute responses, morphological examination of
      exposed roots at the end of the recording period revealed nodal and paranodal
      changes consistent with acute wallerian degeneration in roots stimulated at 50 or
      100 Hz. This interpretation was confirmed in a few experiments that were
      prolonged to permit more obvious indicators of degeneration to develop. In these
      experiments the formation of myelin ovoids and frank axonolysis occurred in more
      than 95% of fibers. Roots stimulated at only 1 Hz appeared normal. We propose
      that the combination of normal impulse traffic and NO at sites of inflammation
      may cause axonal degeneration and that electrical activity may therefore be an
      important factor in causing permanent disability in patients with
      neuroinflammatory disorders.

PMID- 11310625
TI  - Perfusion magnetic resonance abnormalities in patients with sickle cell disease.
AB  - Neurological complications are common in sickle cell disease (SCD). However, it
      is often difficult to relate the clinical presentation to conventional
      neuroimaging, because subclinical infarction is common and stroke has been
      described in the absence of large-vessel disease. We studied 48 patients with SCD
      aged 4-34 (median 13) years with T2-weighted, diffusion and perfusion magnetic
      resonance imaging (MRI) and with MR angiography. Forty-four underwent
      transcranial Doppler (TCD). Abnormalities on perfusion imaging were seen in 25
      cases, 24 of whom had been symptomatic. The remaining patient had evidence of
      executive dysfunction and reduced perfusion in the frontal lobes. The perfusion
      abnormality was larger than the area of infarction in 9 patients and was seen in
      an arterial distribution with no infarction in a further 9. In 3 patients with
      transient ischemic attacks, perfusion abnormalities were demonstrated in the
      absence of any other neuroimaging abnormalities, and perfusion changes were seen
      in 3 others despite normal MR angiography and TCD. Perfusion abnormalities are
      associated with neurological symptoms in patients with SCD, whether or not MRI,
      MR angiography, and TCD are abnormal. It is likely that this technique will guide
      management in individual patients.

PMID- 11310626
TI  - Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder.
AB  - We describe here familial dyskinesia and facial myokymia (FDFM), a novel
      autosomal dominant disorder characterized by adventitious movements that
      sometimes appear choreiform and that are associated with perioral and periorbital
      myokymia. We report a 5-generation family with 18 affected members (10 males and
      8 females) with FDFM. The disorder has an early childhood or adolescent onset.
      The involuntary movements are paroxysmal at early ages, increase in frequency and
      severity, and may become constant in the third decade. Thereafter, there is no
      further deterioration, and there may even be improvement in old age. The
      adventitious movements are worsened by anxiety but not by voluntary movement,
      startle, caffeine, or alcohol. The disease is socially disabling, but there is no
      intellectual impairment or decrease in lifespan. A candidate gene and haplotype
      analysis was performed in 9 affected and 3 unaffected members from 3 generations
      of this family using primers for polymorphic loci closely flanking or within
      genes of interest. We excluded linkage to 11 regions containing genes associated
      with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the
      paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral
      pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease
      locus on 1p that lies in a region containing a cluster of potassium (K+) channel
      genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1
      gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea
      acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the
      paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11.2; 9) the benign
      hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and
      11) the chromosome 19 region that contains several ion channels and the CACNA1A
      gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and
      hemiplegic migraine. Our results provide further evidence of genetic
      heterogeneity in autosomal dominant movement disorders and suggest that a novel
      gene underlies this new condition.

PMID- 11310627
TI  - Mechanisms and predictors of chronic facial pain in lateral medullary infarction.
AB  - The purpose of this study was to identify clinical predictors and anatomical
      structures involved in patients with pain after dorsolateral medullary
      infarction. Eight out of 12 patients (67%) developed poststroke pain within 12
      days to 24 months after infarction. The pain occurred in the ipsilateral face (6
      patients) and/or the contralateral limbs and trunk (5 patients, 3 of whom also
      had facial pain). Ipsilateral facial pain was significantly correlated with lower
      medullary lesions, including those of the spinal trigeminal tract and/or nucleus,
      as documented by magnetic resonance imaging. The R2 blink reflex component was
      abnormal only in patients with facial pain. Likewise, pain and temperature
      sensation in the ipsilateral face was decreased in all patients with facial pain
      but not in patients without pain. Ipsilateral touch sensation in the face was
      also decreased in all patients with facial pain, but the lesions revealed on
      magnetic resonance imaging did not involve the principal sensory nucleus of the
      fifth cranial nerve, and the R1 blink reflex latencies were normal. Although
      facial pain was correlated with lesions of the spinal trigeminal tract and/or
      nucleus, none of the lesions involved the subnucleus caudalis, which contains
      most nociceptive neurons. These findings suggest that facial pain after medullary
      infarction is due to lesions of the lower spinal trigeminal tract (axons of
      primary afferent neurons), leading to deafferentation of spinal trigeminal
      nucleus neurons.

PMID- 11310628
TI  - Familial amyotrophic lateral sclerosis and parkinsonism-dementia complex of the
      Kii Peninsula of Japan: clinical and neuropathological study and tau analysis.
AB  - We report the first case of neuropathologically verified parkinsonism-dementia
      complex of the Kii peninsula, together with the patient's brother, who had
      amyotrophic lateral sclerosis. The propositus woman developed parkinsonism and
      dementia at 63 years of age and died at 70 without displaying clinical features
      of amyotrophic lateral sclerosis. The brain exhibited marked atrophy of the
      frontal and temporal lobes. Microscopically, there were many neurofibrillary
      tangles in the central nervous system, most markedly in the mesial temporal lobe
      and deep nuclei, as well as changes of amyotrophic lateral sclerosis but no
      senile plaques or Lewy bodies. Neurofibrillary tangles exhibited twisted tubule
      structures on electon microscopic examination, and an analysis of insoluble tau
      protein extracted from the fresh brain revealed a 60-, 64-, 68-kD triplet. The
      tau gene exhibited no mutations. Her brother developed progressive bulbar palsy
      type amyotrophic lateral sclerosis at 45 years of age and died at 49 without
      presenting with dementia or parkinsonism. Neuropathological examination revealed
      not only pathologic features of amyotrophic lateral sclerosis but also a moderate
      number of neurofibrillary tangles in the temporal cortex and deep nuclei. The
      siblings were neuropathologically similar despite their different clinical
      manifestations. These findings suggest that amyotrophic lateral sclerosis and
      parkinsonism-dementia complex of this family may be phenotypic variants of a
      tauopathy caused by genetic abnormalities.

PMID- 11310629
TI  - Adrenoleukodystrophy: incidence, new mutation rate, and results of extended
      family screening.
AB  - Utilizing the plasma very long chain fatty acid assay, supplemented by mutation
      analysis and immunofluorescence assay, we determined the number of X-linked
      adrenoleukodystrophy (X-ALD) hemizygotes from the United States identified each
      year in the two laboratories that perform most of the assays in this country: the
      Kennedy Krieger Institute between 1981 and 1998 and the Mayo Clinic Rochester
      from 1996 to 1998. The minimum frequency of hemizygotes identified in the United
      States is estimated to be 1:42,000 and that of hemizygotes plus heterozygotes
      1:16,800. Our studies involved 616 pedigrees with a total of 12,787 identified at
      risk members. Diagnostic assays were performed in 4,169 at-risk persons (33%) and
      included members of the extended family. Only 5% of male probands and 1.7% of X
      ALD hemizygotes were found to have new mutations. The extended family testing led
      to the identification of 594 hemizygotes and 1,270 heterozygotes. Two hundred
      fifty of the newly identified hemizygotes were asymptomatic and represent the
      group in which therapy has the greatest chance of success. Identification of
      heterozygotes provides the opportunity for disease prevention through genetic
      counseling. Diagnostic tests should be offered to all at-risk relatives of X-ALD
      patients and should include members of the extended family.

PMID- 11310630
TI  - Absence of N-acetylaspartate in the human brain: impact on neurospectroscopy?
AB  - N-acetylaspartate (NAA) contributes to the most prominent signal in proton
      magnetic resonance spectroscopy (1H-MRS) of the adult human brain. We report the
      absence of NAA in the brain of a 3-year-old child with neurodevelopmental
      retardation and moderately delayed myelination. Since normal concentration of NAA
      in body fluids is hardly detectable, 1H-MRS is a noninvasive technique for
      identifying neurometabolic diseases with absent NAA. This report puts NAA as a
      neuronal marker to question.

PMID- 11310631
TI  - A novel TRK A (NTRK1) mutation associated with hereditary sensory and autonomic
      neuropathy type V.
AB  - A boy with recurrent pyrexial episodes from early life sustained a painless ankle
      injury and was found to have a calcaneus fracture and, later, neuropathic joint
      degeneration of the tarsus. Examination revealed distal loss of pain and
      temperature sensation and widespread anhidrosis. Sural nerve biopsy demonstrated
      severe reduction in small-caliber myelinated fiber density but only modest
      reduction in unmyelinated axons, the pattern of type V hereditary sensory and
      autonomic neuropathy (HSAN V). DNA analysis showed that he was homozygous for a
      mutation in the NTRK1/high-affinity nerve growth factor (TrkA) gene, his parents
      being heterozygous. Mutations in this gene are known to be responsible for HSAN
      IV (congenital insensitivity to pain with anhidrosis). The two disorders are
      therefore likely to be allelic.

PMID- 11310632
TI  - Subthalamic infusion of an NMDA antagonist prevents basal ganglia metabolic
      changes and nigral degeneration in a rodent model of Parkinson's disease.
AB  - Using permanent cannulas connected to subcutaneous pumps, we infused selective
      glutamate antagonists into the subthalamic nucleus of rats. Pumps were implanted
      immediately after the intrastriatal injection of 6-hydroxydopamine and delivered
      micro-quantities of the Nmethyl-D-aspartate antagonist MK-801 or the alpha-amino
      3-hydroxy-5-methylisoxazole antagonist NBQX for 4 weeks. Subthalamic infusion of
      MK-801, but not of NBQX, prevented the basal ganglia metabolic changes and motor
      abnormalities caused by nigrostriatal lesion. Animals treated with MK-801 also
      exhibited marked reduction of nigral cell loss. We conclude that pharmacological
      modulation of subthalamic activity may have both symptomatic and neuroprotective
      effects in Parkinson's disease.

PMID- 11310633
TI  - Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous
      malformations.
AB  - Mutations in the Kritl gene have been recently discovered as the cause of
      hereditary cerebral cavernous angioma. We sought the possibility that de novo,
      noninherited mutations of Kritl also cause cavernous angioma. A patient with two
      cerebral malformations carries a heterozygous deletion of two base pairs
      (741delTC) in exon VI of the Kritl gene. The deletion initiates a frameshift
      mutation that, 23 amino acids downstream, encodes a TAA stop triplet replacing a
      CAT triplet of histidine at exon VII (H271X). Magnetic resonance images of the
      parents were normal, neither parent carries the 741delTC mutation, and both bear
      the wild-type sequence of exon VI. These findings document a de novo germline
      mutation in Kritl gene that causes cerebral cavernous malformations.

PMID- 11310634
TI  - Abnormal desmin protein in myofibrillar myopathies caused by desmin gene
      mutations.
AB  - Muscle proteins were extracted in various sodium dodecyl sulfate buffers from 6
      patients with myofibrillar myopathy (MFM) and previously identified with
      mutations in the desmin gene (desmin myopathy; DesM), 6 with MFM without
      mutations, and 14 disease controls to search for alterations in biochemistry and
      solubility of mutated desmin filaments. In the 1% posthigh-speed pellet fraction,
      desmin was detected with immunoblots only in DesM and not the other MFM. We
      conclude that mutant desmin forms insoluble aggregates that are specific for the
      DesM and can be detected with Western blots.

PMID- 11310635
TI  - Effects of riluzole on cortical excitability in patients with amyotrophic lateral
      sclerosis.
AB  - Using transcranial magnetic stimulation, the effect of riluzole (RLZ) on cortical
      excitability was studied in patients with amyotrophic lateral sclerosis (ALS).
      Paired-pulse inhibition (PPI) and paired-pulse facilitation (PPF) were reduced.
      RLZ partially restored deficient PPI in the first of 4 consecutive 3-month
      periods of testing, but left PPF unchanged. These findings substantiate the view
      that attenuation of glutamate-related excitotoxicity is an important factor
      contributing to the beneficial effect of RLZ in ALS.

PMID- 11310636
TI  - Gluten sensitivity in sporadic and hereditary cerebellar ataxia.
AB  - Gluten sensitivity, with or without classical celiac disease symptoms and
      intestinal pathology, has been suggested as a potentially treatable cause of
      sporadic cerebellar ataxia. Here, we investigated the prevalence of abnormally
      high serum immunoglobulin A (IgA) and IgG anti-gliadin antibody titers and
      typical human lymphocyte antigen (HLA) genotypes in 50 patients presenting with
      cerebellar ataxia who were tested for molecularly characterized hereditary
      ataxias. A high prevalence of gluten sensitivity was found in patients with
      sporadic (7/26; 27%) and autosomal dominant (9/24; 37%) ataxias, including
      patients with known ataxia genotypes indicating a hitherto unrecognized
      association between hereditary ataxias and gluten sensitivity. Further studies
      are needed to determine whether gluten sensitivity contributes to cerebellar
      degeneration in patients with hereditary cerebellar ataxia. Patients with
      hereditary ataxia (including asymptomatic patients with known ataxia genotype)
      should be considered for screening for gluten sensitivity and gluten-free diet
      trials.

PMID- 11310637
TI  - Collagen VI deficiency in Ullrich's disease.

PMID- 11310638
TI  - Cathepsin D polymorphism not associated with Alzheimer's disease in Japanese.

PMID- 11310639
TI  - Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein
      phosphorylated at threonine 231.

PMID- 11310640
TI  - Plasma levels of amyloid beta proteins did not differ between subjects taking
      statins and those not taking statins.

PMID- 11310641
TI  - Intratumor heterogeneity of k-ras and p53 mutations among human colorectal
      adenomas containing early cancer.
AB  - The molecular pathways and the timing of genetic events during human colorectal
      carcinogenesis are still not fully understood. We have addressed the intratumor
      heterogeneity of the mutational status of the k-ras oncogene and of the p53
      oncosuppressor gene during the adenoma-carcinoma sequence by investigating 26
      human colorectal adenomas containing early cancer. An intratumor comparative
      analysis was obtained among the adenomatous and carcinomatous component pairs.
      Additionally, we have analyzed 17 adenomas having cancer in the near vicinity.
      The adenomatous components of the adenomas containing early cancer and the
      adenomas having cancer in the near vicinity had comparable frequencies for k-ras
      mutations (28 and 47%) but different for p53 mutations (52 and 7%, p-value =
      0.01). Interestingly, the adenomatous and carcinomatous components of the
      adenomas containing early cancer were rarely heterogeneous for the k-ras
      mutational status (only in 13% of the cases) but were characterized by
      heterogeneity of the p53 status in 59% of the cases (p-value < 0.01). In
      addition, the mutations of p53 for the adenomatous components of the adenomas
      containing early cancer were statistically significantly associated with severe
      dysplasia (p-value = 0.01). Intratumor homogeneity of k-ras status during the
      human colorectal adenoma-carcinoma sequence suggests that the role of k-ras is
      more related to tumor initiation than to tumor progression. On the contrary,
      intratumor heterogeneity of p53 mutations indicates that the type of the p53
      mutations may also be relevant for selection and expansion of new subclones
      leading to tumor progression.

PMID- 11310642
TI  - Caveats: numerical requirements in graph theory based quantitation of tissue
      architecture.
AB  - Graph theory based methods represent one approach to an objective and
      reproducible structural analysis of tissue architecture. By these methods,
      neighborhood relations between a number of objects (e.g., cells) are explored and
      inherent to these methods are therefore certain requirements as to the number of
      objects to be included in the analysis. However, the question of how many objects
      are required to achieve reproducible values in repeated computations of proposed
      structural features, has previously not been adressed specifically. After
      digitising HE stained slides and storing them as grey level images, cell nuclei
      were segmented and their geometrical centre of gravity were computed, serving as
      the basis for construction of the Voronoi diagram (VD) and its subgraphs.
      Variations in repeated computations of structural features derived from these
      graphs were related to the number of cell nuclei included in the analysis. We
      demonstrate a large variation in the values of the structural features from one
      computation to another in one and the same section when only a limited number of
      cells (100-500) are included in the analysis. This variation decreased with
      increasing number of cells analyzed. The exact number of cells required to
      achieve reproducible values differ significantly between tissues, but not between
      separate cases of similar lesions. There are no significant differences between
      normal and malignantly changed tissues in oral mucosa with respect to how many
      cells must be included. For graph theory based analysis of tissue architecture,
      care must be taken to include an adequate number of objects; for some of the
      structural features we have tested, more than 3000 cells.

PMID- 11310643
TI  - New algorithms based on the Voronoi Diagram applied in a pilot study on normal
      mucosa and carcinomas.
AB  - An adequate reproducibility in the description of tissue architecture is still a
      challenge to diagnostic pathology, sometimes with unfortunate prognostic
      implications. To assess a possible diagnostic and prognostic value of
      quantitiative tissue architecture analysis, structural features based on the
      Voronoi Diagram (VD) and its subgraphs were developed and tested. A series of 27
      structural features were developed and tested in a pilot study of 30 cases of
      prostate cancer, 10 cases of cervical carcinomas, 8 cases of tongue cancer and 8
      cases of normal oral mucosa. Grey level images were acquired from hematoxyline
      eosine (HE) stained sections by a charge coupled device (CCD) camera mounted on a
      microscope connected to a personal computer (PC) with an image array processor.
      From the grey level images obtained, cell nuclei were automatically segmented and
      the geometrical centres of cell nuclei were computed. The resulting 2-dimensional
      (2D) swarm of pointlike seeds distributed in a flat plane was the basis for
      construction of the VD and its subgraphs. From the polygons, triangulations and
      arborizations thus obtained, 27 structural features were computed as numerical
      values. Comparison of groups (normal vs. cancerous oral mucosa, cervical and
      prostate carcinomas with good and poor prognosis) with regard to distribution in
      the values of the structural features was performed with Student's t-test. We
      demonstrate that some of the structural features developed are able to
      distinguish structurally between normal and cancerous oral mucosa (P = 0.001),
      and between good and poor outcome groups in prostatic (P = 0.001) and cervical
      carcinomas (P = 0.001). We present results confirming previous findings that
      graph theory based algorithms are useful tools for describing tissue architecture
      (e.g., normal versus malignant). The present study also indicates that these
      methods have a potential for prognostication in malignant epithelial lesions.

PMID- 11310644
TI  - Programmed cell death, proliferating cell nuclear antigen and p53 expression in
      mouse colon mucosa during diet-induced tumorigenesis.
AB  - Western-style diets (WDs) trigger and sustain the early phases of tumorigenesis
      in mouse colon, and when continued throughout the life span lead to the
      development of dysplastic crypts. In order to evaluate the roles both of cell
      proliferation and programmed cell death (PCD) in WD-induced tumorigenesis,
      immunohistochemical detection of proliferating nuclear antigen (PCNA), in situ
      end labeling (TUNEL) of DNA breaks, and p53 protein were carried out in mouse
      colonic mucosa during prolonged feeding of two WDs. PCNA Labeling Index of
      colonic crypts was significantly higher in WD-treated animals than in controls
      only at the beginning of the nutritional study, the gap rapidly bridged by
      increased cell proliferation spontaneously occurring in the colonic mucosa during
      aging. A transient early homeostatic activation of PCD at the base of the crypt
      also was observed in WD groups. No changes in PCD were seen in the upper third of
      the crypt or in surface epithelium throughout the study, indicating that PCD in
      that colonic crypt segment produces a constant flux of cell loss, uninfluenced by
      homeostatic fluctuations. A major finding was an irreversible, progressive, age
      related decline of PCD at the crypt base in both control and treated animals that
      occurred during the second half of the rodents' life span. p53 protein was not
      immunohistochemically detected, suggesting that neither overexpression of wild
      type nor mutated forms of the protein are involved in the above mentioned
      changes.

PMID- 11310645
TI  - Cardiovascular disease and differences between the sexes.

PMID- 11310646
TI  - No-needle anesthetic for no-scalpel vasectomy.

PMID- 11310647
TI  - Family physicians as specialists.

PMID- 11310648
TI  - Diagnosis and initial management of kidney stones.
AB  - The diagnosis and initial management of urolithiasis have undergone considerable
      evolution in recent years. The application of noncontrast helical computed
      tomography (CT) in patients with suspected renal colic is one major advance. The
      superior sensitivity and specificity of helical CT allow urolithiasis to be
      diagnosed or excluded definitively and expeditiously without the potential
      harmful effects of contrast media. Initial management is based on three key
      concepts: (1) the recognition of urgent and emergency requirements for urologic
      consultation, (2) the provision of effective pain control using a combination of
      narcotics and nonsteroidal anti-inflammatory drugs in appropriate patients and
      (3) an understanding of the impact of stone location and size on natural history
      and definitive urologic management. These concepts are discussed with reference
      to contemporary literature, with the goal of providing tools that family
      physicians can use in the emergency department or clinic.

PMID- 11310649
TI  - Management of asthma in children.
AB  - The prevalence of asthma in children has increased 160 percent since 1980, and
      the disease currently affects nearly 5 million children in the United States. The
      National Asthma Education and Prevention Program provides guidelines for improved
      asthma care. The goals of this program are to limit the frequency, severity and
      costliness of asthma exacerbations through extensive education of physicians,
      children and caregivers. The four components of asthma management include regular
      assessment and monitoring, control of factors that contribute to or aggravate
      symptoms, pharmacologic therapy and education of children and their caregivers.
      The guidelines recommend a stepwise approach to pharmacologic treatment, starting
      with aggressive therapy to achieve control and followed by a "step down" to the
      minimal therapy that will maintain control. Quick relief of symptoms can be
      achieved preferentially by the use of short-acting beta2 agonists. Medications
      for long-term control should be considered for use in children with persistent
      symptoms. Inhaled corticosteroids are the most potent long-term anti-inflammatory
      medications. Other options include long-acting beta2 agonists, cromolyn sodium
      and nedocromil, antileukotriene agents and theophylline. All have advantages and
      disadvantages in individual situations.

PMID- 11310650
TI  - Diagnosis and management of malignant melanoma.
AB  - The incidence of malignant melanoma has increased in recent years more than that
      of any other cancer in the United States. About one in 70 people will develop
      melanoma during their lifetime. Family physicians should be aware that a patient
      with a changing mole, an atypical mole or multiple nevi is at considerable risk
      for developing melanoma. Any mole that is suggestive of melanoma requires an
      excisional biopsy, primarily because prognosis and treatment are based on tumor
      thickness. Staging is based on tumor thickness (Breslow's measurement) and
      histologic level of invasion (Clark level). The current recommendations for
      excisional removal of confirmed melanomas include 1-cm margins for lesions
      measuring 1.0 mm or less in thickness and 2-cm margins for lesions from 1.0 mm to
      4.0 mm in thickness or Clark's level IV of any thickness. No evidence currently
      shows that wider margins improve survival in patients with lesions more than 4.0
      mm thick. Clinically positive nodes are typically managed by completely removing
      lymph nodes in the area. Elective lymph node dissection is recommended only for
      patients who are younger than 60 years with lesions between 1.5 mm and 4.0 mm in
      thickness. In the Eastern Cooperative Oncology Group Trial, interferon alfa-2b
      was shown to improve disease-free and overall survival, but in many other trials
      it has not been shown to be effective at prolonging overall survival. Vaccine
      therapy is currently being used to stimulate the immune system of melanoma
      patients with metastatic disease.

PMID- 11310651
TI  - Flexible sigmoidoscopy.
AB  - Flexible sigmoidoscopy remains a common tool used for the periodic screening of
      colorectal cancer. Most organizations recommend screening at three- to five-year
      intervals beginning at age 50 for persons with average risk. Extensive training
      in endoscopic maneuvering, colorectal anatomy and pathologic recognition is
      required. Most physicians report comfort performing the procedure unsupervised
      after 10 to 25 precepted sessions. The procedure involves the insertion of the
      sigmoidoscope through the anus and distal rectum and advancement of the scope tip
      to an average depth of 48 to 55 cm in the sigmoid colon. Once the sigmoidoscope
      has been appropriately advanced, the scope is slowly withdrawn, allowing for the
      inspection of colon mucosa during withdrawal. Polyps less than 5 mm in diameter
      should be biopsied. Polyps 5 to 10 mm or greater can be assumed to be
      adenomatous, and follow-up colonoscopy for complete polypectomy is required.
      Diverticulosis, hemorrhoids, nonspecific colitis and pseudomembranes may also be
      encountered during inspection. Use of preprocedural benzodiazepines can be
      helpful in reducing patient discomfort. 2001;63:1375-80,1383-4,1385-8.)

PMID- 11310652
TI  - Coronary artery disease prevention: what's different for women?
AB  - Cardiovascular disease is the leading cause of death in women, as well as an
      important cause of disability, although many women and their physicians
      underestimate the risk. Exercise, hypertension treatment, smoking cessation and
      aspirin therapy are effective measures for the primary prevention of coronary
      artery disease in women. The roles of lipid-lowering agents and hormone
      replacement therapy in primary prevention are not well established. In secondary
      prevention, hormone replacement therapy has not been effective in lowering the
      risk of recurrent myocardial infarction, but several lipid-lowering agents have
      been shown to reduce this risk and to lower mortality rates in women with known
      coronary artery disease. Other secondary prevention measures, including aspirin,
      beta blockers, angiotensin-converting enzyme inhibitors, revascularization and
      rehabilitation, have proven benefits in women but are underused, especially in
      minority women. Family physicians should emphasize the use of proven treatments,
      with particular attention given to underserved populations.

PMID- 11310653
TI  - Photo quiz. Blue-gray centrofacial hyperpigmentation.

PMID- 11310654
TI  - NIH consensus statement on phenylketonuria.

PMID- 11310655
TI  - What should physicians tell about themselves to patients?

PMID- 11310656
TI  - Structure-activity relationship (SAR) studies on oxazolidinone antibacterial
      agents. 1. Conversion of 5-substituent on oxazolidinone.
AB  - A structure-activity relationship (SAR) study on 5-substituted oxazolidinones as
      an antibacterial agent is described. The oxazolidinones, of which 5
      acetylaminomethyl moiety was converted into other functions, were prepared and
      evaluated for antibacterial activity. Elongation of the methylene chain (8) and
      conversion of the acetamido moiety into guanidino moiety (12) decreased the
      antibacterial activity. The replacement of carbonyl oxygen (=O) by thiocarbonyl
      sulfur (=S) enhanced in vitro antibacterial activity. Especially, compound 16,
      which had the 5-thiourea group, showed 4-8 stronger in vitro activity than
      linezolid. Our SAR study revealed that the antibacterial activity was greatly
      affected by the conversion of 5-substituent.

PMID- 11310657
TI  - Structure-activity relationship (SAR) studies on oxazolidinone antibacterial
      agents. 2. Relationship between lipophilicity and antibacterial activity in 5
      thiocarbonyl oxazolidinones.
AB  - 5-Thiourea and 5-dithiocarbamate oxazolidinones were synthesized as a
      continuation of research on 5-thiocarbonyl oxazolidinone antibacterial agents
      considering the hydrophobic parameters of the molecule. The structure-activity
      relationship (SAR) study revealed that the antibacterial activity on 5
      thiocarbonyl oxazolidinones was significantly affected by the lipophilicity,
      especially the calculated log P value and the balance between 5-hydrophilic (or
      hydrophobic) substituent and hydrophobic (or hydrophilic) substituents on the
      benzene ring. Some of 5-thiocarbonyl oxazolidinones were found to have good in
      vitro antibacterial activity against gram-positive bacteria including methicillin
      resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci
      (VRE).

PMID- 11310658
TI  - Structure-activity relationship (SAR) studies on oxazolidinone antibacterial
      agents. 3. Synthesis and evaluation of 5-thiocarbamate oxazolidinones.
AB  - A series of 5-thiocarbamate oxazolidinones was prepared and tested for in vitro
      and in vivo antibacterial activities. The results of in vitro antibacterial
      activity indicated that the 5-thiocarbamate group was a suitable substituent for
      the activity by the 5-moderate hydrophilicity. The compounds within a favorable
      logP value range were found to have potent in vitro antibacterial activity
      against gram-positive bacteria including methicillin-resistant Staphylococcus
      aureus (MRSA) and vancomycin-resistant enterococci (VRE). Compounds 3a and 4h
      were superior to linezolid in both in vitro and in vivo potency and were
      considered to be hopeful compounds. We also discuss the pharmacokinetic
      properties of several compounds in mice.

PMID- 11310659
TI  - Photochemical and oxidative degradation of the solid-state tretinoin tocoferil.
AB  - The photostability of tretinoin tocoferil was investigated under irradiation with
      three kinds of lamps, i.e., a cool white fluorescent lamp, a UV-A fluorescent
      lamp and a D65 fluorescent lamp. A combination of the cool white fluorescent lamp
      and the UV-A fluorescent lamp, and the D65 lamp having relative spectral power
      distribution similar to that of direct daylight, correspond to options 2 and 1 in
      ICH Guidelines, respectively. The photodegradation apparently followed second
      order kinetics under these light sources and the degradation rate constant under
      exposure by the D65 lamp was larger than that by the cool white fluorescent lamp.
      The drug was susceptible to degradation by visible and UV light below 480 nm and
      was degraded most remarkably at around 420 nm, showing a wavelength-dependency.
      The semi-logarithmic plots of apparent degradation rate constant against the
      reciprocal of illuminance showed a good linear relationship in the Arrhenius-type
      fashion, and the photostability under ordinary illumination conditions could be
      predicted from the data obtained under the accelerated illumination conditions.
      The rate of oxidative degradation was slightly accelerated with the rise of
      temperature. Thermodynamic parameter was calculated from the Arrhenius plot. The
      degradation rate constant rapidly increased in proportion to partial pressure of
      oxygen below 20 kPa.

PMID- 11310660
TI  - Interaction of microcrystalline cellulose and water in granules prepared by a
      high-shear mixer.
AB  - Microcrystalline cellulose (MCC) granules were prepared by wet granulation using
      a high-shear mixer. Physical characteristics of the granules were investigated
      using near IR spectrometry, thermogravimetry and isothermal water vapor
      adsorption. Near IR spectra of dried MCC granules prepared for various
      granulation times exhibited different peak intensities at 1428, 1772, and 1920
      nm, which were assigned to functional groups of cellulose or water. On
      isothermogravimetric analysis, the rate of dehydration of water was shown to
      decrease with granulation time. These results suggest that the physical structure
      of MCC could change during the granulation process, and the interaction between
      MCC and water was gradually strengthened. The isothermal water vapor adsorption
      curves suggested that the amorphous region of MCC would be divided by the strong
      shear force of the impeller, because the high adsorption ability of intact MCC in
      the low humidity region was diminished in granules collected following 5 and 10
      min of granulation. It was suggested that MCC formed a network which caught water
      within its structure during the wet granulation process.

PMID- 11310661
TI  - Synthesis and anti-influenza virus activity of tricyclic compounds with a unique
      amine moiety.
AB  - Several novel tricyclic compounds with a unique amine moiety (1, 2a--i) were
      designed and prepared based on the structure of triperiden for the development of
      anti-influenza virus agents. An in vitro antiviral assay showed that 1-(1
      azabicyclo[3.3.0]octan-5-yl)-1-(4-fluorophenyl)-1-(2
      tricyclo[3.3.1.1(3.7)]decyl)methan-1-ol hydrochloride (2f) has a potent anti
      influenza A virus activity. Furthermore, since 2f was well tolerated in mice, 2f
      is promising as a novel anti-influenza virus agent for humans.

PMID- 11310662
TI  - Acid-catalyzed photoreaction of 6-chloro-1,3-dimethyluracil and mesitylene:
      formation of photocycloadducts and their characterization.
AB  - In contrast to the previously reported short time required (1 h) for photolysis
      of 6-chloro-1,3-dimethyluracil (6-CIDMU) and mesitylene, in the presence of TFA,
      resulting in two major products: 1,3,6,8,10-pentamethylcyclooctapyrimidine
      derivative (1d), and diazapentacyclo[6.4.0.0(1,3).0(2,5).0(4,8)]dodecane (2c),
      prolonged irradiation (18h) of this same mixture yields novel pentalenopyrimidine
      derivatives, including diazapentacyclo[6.4.0.0(1,3).0(2,6).0(4,8)]dodecane (3c).

PMID- 11310663
TI  - Synthesis of new fused pyrimidines by isocyanate and isothiocyanate.
AB  - o-Aminonitrile or o-aminoester compounds were cyclized to fused pyrimidines by
      reacting with ethyl iso(thio)cyanatoacetate in pyridine, and then were
      methylated, halogenated and subsequently displaced by the amines studied.

PMID- 11310664
TI  - Prolyl endopeptidase inhibitors from the underground part of Rhodiola
      sachalinensis.
AB  - The methanolic extract of the underground part of Rhodiola sachalinensis was
      found to show inhibitory activity on prolyl endopeptidase (PEP, EC. 3.4.21.26),
      an enzyme that plays a role in the metabolism of proline-containing
      neuropeptidase which is recognized to be involved in learning and memory. From
      the MeOH extract, five new monoterpenoids named sachalinols A (24), B (25) and C
      (26) and sachalinosides A (23) and B (27) were isolated, together with twenty-two
      known compounds, gallic acid (1), trans-p-hydroxycinnamic acid (2), p-tyrosol
      (3), salidroside (4), 6n-O-galloylsalidroside (5), benzyl beta-D-glucopyranoside
      (6), 2-phenylethyl beta-D-glucopyranoside (7), trans-cinnamyl beta-D
      glucopyranoside (8), rosarin (9), rhodiocyanoside A (10), lotaustralin (11),
      octyl beta-D-glucopyranoside (12), 1,2,3,6-tetra-O-galloyl-beta-D-glucose (13),
      1,2,3,4,6-penta-O-galloyl-beta-D-glucose (14), kaempferol (15), kaempferol 3-O
      beta-D-xylofuranosyl(1-->2)-beta-D-glucopyranoside (16), kaempferol 3-O-beta-D
      glucopyranosyl(1-->2)-beta-D-glucopyranoside (17), rhodionin (18), rhodiosin
      (19), (-)-epigallocatechin (20), 3-O-galloylepigallocatechin-(4-->8)
      epigallocatechin 3-O-gallate (21) and rosiridin (22). Among these, nineteen
      compounds other than 3, 4 and 9 have been isolated for the first time from R.
      sachalinensis, and six (6, 8, 13, 16, 17, 20) are isolated from Rhodiola plants
      for the first time. Among them, six compounds (13, 14, 18, 19, 21, 22) showed
      noncompetitive inhibition against Flavobacterium PEP, with an IC50 of 0.025,
      0.17, 22, 41, 0.44 and 84 microM, respectively.

PMID- 11310665
TI  - Reaction kinetics of solid-state cyclization of enalapril maleate investigated by
      isothermal FT-IR microscopic system.
AB  - To investigate the reaction kinetics of the solid-state degradation process of
      enalapril maleate, a Fourier transform infrared microspectroscope equipped with
      thermal analyzer (thermal FT-IR microscopic system) was used. The isothermal
      stability study was conducted at 120-130 degrees C for 1-2 h and changes in the
      three-dimensional plots of the IR spectra of enalapril maleate with respect to
      heating time were observed. The study indicates that the bands at 1649, 1728, and
      1751 cm(-1) assigned to intact enalapril maleate gradually reduced in peak
      intensity with heating time. However, the peak intensities at 1672 and 1738 cm(
      1) (due to enalapril diketopiperazine (DKP) formation) and at 3250 cm(-1)
      (corresponding to water formation) gradually increased with heating time. The
      solid-state diketopiperazine formation and the degradation process of enalapril
      maleate via intramolecular cyclization were found to be simultaneous. The
      isothermal decomposition curves were sigmoidal and were characterized by
      induction and acceleration periods, indicating the presence of autocatalytic
      solid-state decompositions. Moreover, the power-law equation (n = 1/4) was found
      to provide the best fit to the kinetics of decomposition. This isothermal FT-IR
      microscopic system was easily used to investigate the degradation of enalapril
      maleate and the concomitant formation of DKP. The solid-state reaction of
      enalapril maleate required an activation energy of 195+/-12 kJ/mol to undergo the
      processes of decomposition and intramolecular cyclization.

PMID- 11310666
TI  - Synthesis of phenanthridones using Diels-Alder reactions of 4-substituted 2(1H)
      quinolones acting as dienophiles.
AB  - Diels-Alder reactions of 2(1H)-quinolones having an electron-withdrawing group at
      the 4-position with 1,3-butadiene derivatives were carried out to give the
      phenanthridones richly functionalized under the conditions of atmospheric and
      high pressure. Furthermore, the reactivities of 4-substituted 2(1H)-quinolones
      acting as a dienophile were examined using MO calculation.

PMID- 11310667
TI  - Viewing of complex molecules of ethidium bromide and plasmid DNA in solution by
      atomic force microscopy.
AB  - Tertiary structure changes in plasmid DNA, induced by ethidium bromide
      intercalation, have been observed in aqueous solutions by the use of an atomic
      force microscope. A relaxed closed circular pBR322 molecule became a positively
      supercoiled complex on the drug binding. The supercoiling always resulted in an
      interwound (or a plectonemic) form, but never a solenoidal (or a toroidal) form.
      A quantitative analysis of the compactness of such supercoiled complexes has been
      carried out.

PMID- 11310668
TI  - The molecular and crystal structure of tert-butyl Nalpha-tert-butoxycarbonyl-L-(S
      trityl)cysteinate and the conformation-stabilizing function of weak
      intermolecular bonding.
AB  - The title compound, C31H37NO4S [systematic name: (R)-tert-butyl-2-[(tert
      butoxycarbonyl)amino]-3-(tritylsulfanyl)propanoate] is an L-cysteine derivative
      with three functions: NH2, COOH and SH, blocked by protecting groups tert
      butoxycarbonyl, tert-butyl and trityl, respectively. The main chain of the
      molecule adopts the extended, nearly all-trans C5 conformation with the
      intramolecular N-H...O=C hydrogen bond. The urethane group is not involved in any
      intermolecular hydrogen bonding. Only weak intermolecular hydrogen bonds and
      hydrophobic contacts are observed in the crystal structure. These are C-H...O
      hydrogen bonds and CH/pi interactions with donor...acceptor distances, C...O ca.
      3.5 A and C...C ca. 3.7 A, respectively. The first type of interaction links
      phenyl H-atoms and carbonyl groups. The second type of interaction is formed
      between a methyl group of the tert-butyl fragment and a trityl phenyl ring. The
      resulting molecular conformation in the crystal is very close to an ab initio
      minimum energy conformer of the isolated molecule. The extended C5 conformation
      of the main peptide chain is the same and there is slight discrepancy in the
      disposition of trityl phenyl rings. Their small dislocation creates the
      possibility of forming the entire network above of extensive, specific, weak
      intermolecular interactions; these constrain the molecule and permit it to retain
      the minimum energy C5 conformation of its main chain in the solid state. In
      contrast, in n-hexane solution, where such specific interactions cannot occur,
      only a small population of the molecules adopts the extended C5 conformation.

PMID- 11310669
TI  - Synthesis and gastrointestinal prokinetic activity of novel benzamide derivatives
      with amphoteric side chains.
AB  - Novel benzamide derivatives (19-24, 32a-c, 43d-f), each possessing a
      cycloaminoalkanecarboxylic acid side chain, were synthesized and their
      gastrointestinal prokinetic and dopamine D2 receptor antagonist activities were
      evaluated. 4-[(4-Amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetic acid
      (19) exhibited the most potent gastro- and colon-prokinetic activities, through
      intravenous administration to conscious dogs, and also showed the reduced
      dopamine D2 receptor antagonistic activity. However, 19 showed only weak
      gastrointestinal prokinetic activity after oral administration. Several ester
      prodrugs (44-62) of 19 were tested for pharmacological activities as well as
      physicochemical and metabolic stability; the butyl ester (46) was consequently
      selected as a promising gastrointestinal prokinetic agent with reduced side
      effects.

PMID- 11310670
TI  - Studies on the constituents of Cimicifuga species. XXVIII. Cycloart-7-enol
      glycosides from the underground parts of Cimicifuga simplex Wormsk.
AB  - Four new cycloart-7-ene triterpenol arabinosides, bugbanosides C-F, were isolated
      from the underground parts of Cimicifuga simplex Wormsk. (Ranunculaceae). The
      structures were elucidated as 12beta-acetoxy-3beta,15alpha,-24R,25-tetrahydroxy
      16,23-dione-cycloart-7-ene 3-O-alpha-arabinopyranoside, 12beta-acetoxy-24R,25
      epoxy-3beta,15alpha-dihydroxy-16,23-dione-cycloart-7-ene 3-O-alpha-L
      arabinopyranoside, 12beta-acetoxy-24R,25-epoxy-3beta-hydroxy-16,23-dione-cycloart
      7-ene 3-O-alpha-L-arabinopyranoside, and 16,23R:16,24S-diepoxy
      3beta,12beta,15alpha,25-tetrahydroxy-cycloart-7-ene 3-O-alpha-L-arabinopyranoside
      on the basis of spectral and chemical evidence. The circular dichroism (CD) of
      bugbanosides C-F showed strong negative maxima at 214-217 nm due to a cycloart-7
      ene system, as well as other cycloart-7-ene triterpenes. The CD data showed to be
      useful in determining basic skeletons, including absolute stereostructures of
      cycloart-7-ene triterpenes.

PMID- 11310671
TI  - Six new dammarane-type triterpene saponins from the leaves of Panax ginseng.
AB  - Six new minor saponins, together with known ginsenosides, were isolated from the
      leaves of Panax ginseng. The new saponins were named as ginsenoside-Rh5, -Rh6, 
      Rh7 -Rh8, -Rh9 and -Rg7, and their structures were elucidated on the basis of
      chemical and physicochemical evidence to be as follows: ginsenoside-Rh5:
      3beta,6alpha,12beta,24zeta-tetrahydroxy-dammar-20(22),25-diene 6-O-beta-D
      glucopyranoside (1), -Rh6: 3beta,6alpha12beta,20(S)-tetrahydroxy-25-hydroperoxy
      dammar-23-ene 20-O-beta-D-glucopyranoside (2), -Rh7: 3beta,7beta,12beta,20(S)
      tetrahydroxy-dammar-5,24-diene 20-O-beta-D-glucopyranoside (3), -Rh8:
      3beta,6alpha,20(S)-trihydroxy-dammar-24-ene-12-one 20-O-beta-D-glucopyranoside
      (4), -Rh9: 3beta,6alpha,20(S)-trihydroxy-12beta,23-epoxy-dammar-24-ene 20-O-beta
      D-glucopyranoside (5) and -Rg7: 3-O-beta-D-glucopyranosyl
      3beta,12beta,20(S),24(R)-tetrahydroxy-dammar-25-ene 20-O-beta-D-glucopyranoside
      (6).

PMID- 11310672
TI  - Constituents of holothuroidea. 10. Isolation and structure of a biologically
      active ganglioside molecular species from the sea cucumber Holothuria
      leucospilota.
AB  - Three ganglioside molecular species, HLG-1 (1), HLG-2 (2), and HLG-3 (3) have
      been obtained from the lipid fraction of the chloroform/methanol extract of the
      sea cucumber Holothuria leucospilota. The structures of these gangliosides have
      been determined, on the basis of chemical and spectroscopic evidence, as 1-O-[(N
      glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (1), 1-O
      [(N-glycolyl-alpha-D-neuraminosyl)-(2-->4)-(N-acetyl-alpha-D-neuraminosyl)-(2-
      >6)-beta-D-glucopyranosyl]-ceramide (2) and 1-O-[alpha-L-fucopyranosyl-(1-->11)
      (N-glycolyl-alpha-D-neuraminosyl)-neuraminosyl)-(2-->4)-(N-aetyl-alpha-D
      neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moieties
      were composed of heterogeneous phytosphingosine, sphingosine and 2-hydroxy fatty
      acid units. Compounds 2 and 3 represent new ganglioside molecular species. These
      three ganglioside molecular species showed neuritogenic activity toward the rat
      pheochromocytoma cell line, PC-12 cell, in the presence of NGF (nerve growth
      factor).

PMID- 11310673
TI  - Sweet pregnane glycosides from Telosma procumbens.
AB  - An intensely sweet polyoxypregnane glycoside, telosmoside A15 (15), was isolated
      from an Asian Asclepiadaceae plant, Telosma procumbens, collected in Vietnam.
      This is the first time a sweet pregnane glycoside has been found, and its
      sweetness intensity is 1000 times greater than that of sucrose. From the same
      plant, 17 other new glycosides were isolated, having the same aglycone; they are
      named telosmosides A1-A14 (1-14) and A16-A18 (16-18). Some of these glycosides
      are also sweet, but others are tasteless or bitter. Chemical structures of the 18
      glycosides were determined, and the structure-taste relationship was discussed.

PMID- 11310674
TI  - Convenient synthesis of 4-trifluoromethyl-substituted imidazole derivatives.
AB  - Mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates (1), obtained from the
      reaction of N-acyl-N-alkylglycines (2) with trifluoroacetic anhydride, react with
      ammonia to give 4-trifluoromethyl-3,4-dihydroimidazoles (3) in high yields.
      Dehydration of 3 gives 4-trifluoromethylimidazoles (4) in high yields. The novel
      ring transformation of 1 into 3 occurs via a regioselective attack of ammonia on
      the C-2 position of the ring.

PMID- 11310675
TI  - Analysis of the marker compounds of Rhodiola rosea L. (golden root) by reversed
      phase high performance liquid chromatography.
AB  - An HPLC method permitting the first simultaneous detection of 5 marker compounds
      (salidroside, rosarin, rosavin, rosin, rosiridin) of R. rosea was developed. A
      separation was achieved within 27 min by using C-18 column material, a phosphate
      buffer/acetonitrile gradient system and at a separation temperature of 60 degrees
      C. All five compounds could be detected at concentrations as low as 0.62
      microg/ml and were clearly assignable in R. rosea plant material and commercial
      products. Therefore, this quantitative and qualitative applicability of the
      method offers efficient and reliable means for the evaluation of R. rosea and
      products thereof.

PMID- 11310676
TI  - Stereoselective reactions. XXXIV. Enantioselective deprotonation of prochiral 4
      substituted cyclohexanones using chiral bidentate lithium amides having a bulky
      group instead of a phenyl group on the chiral carbon.
AB  - Using chiral bidentate lithium amides having a bulky group instead of a phenyl
      group on the chiral carbon, enantioselective deprotonation of prochiral 4
      substituted cyclohexanones in the presence of excess trimethylsilyl chloride was
      examined in THF in the absence and in the presence of HMPA. It is shown that
      enantioselectivity of the reactions decreases as the substituent on the chiral
      carbon of the chiral lithium amides and the substituent at the 4-position of
      cyclohexanones become reasonably bulky. An eight-membered cyclic transition state
      model is proposed for this deprotonation reaction.

PMID- 11310677
TI  - Ab initio molecular orbital study of reactivity of active alkyl groups. IV.
      Nitrosation of acyclic carbonyl compound with methyl nitrite via "open-chain"
      transition state.
AB  - The mechanism of the nitrosation of enolate anion of acetone [CH3COCH2]- (1) with
      methyl nitrite CH3ONO (2) via an "open-chain" transition state without Na+ in the
      C-N bond formation process was studied by the ab initio MO method. The complex
      [CH3COCH2NO(OCH3)]- (C-II) was first formed from the adduct (C-I) of 1 and 2
      through the transition state (TSI). Finally, E-1-hydroxyimino-2-oxo-propane
      CH3COCH=NOH (3E), together with Z-form (3Z), was obtained by way of the
      elimination process. It has become apparent that 3E is formed when C-II-A is
      produced in the C-N bond formation process.

PMID- 11310678
TI  - Practical synthesis of a 1beta-methylcarbapenem, J-111,225, using 4-mercapto-2-[4
      (N-methylaminomethyl)phenyl]pyrrolidine as a precursor.
AB  - An effective and practical procedure for the synthesis of J-111,225 (1), a new
      1beta-methylcarbapenem, was developed using 4-mercapto-2-14-(N
      methylaminomethyl)phenyl]pyrrolidine (2a) as a precursor. The coupling reaction
      of 2a with p-nitrobenzyl (PNB)-protected 1beta-methylcarbapenem enolphosphate 3a
      and successive removal of PNB group afforded J-111,225 (1) in significantly
      increased yield compared to the ordinary procedure using a C-2 side-chain thiol
      with amino-protective groups.

PMID- 11310679
TI  - Synthesis of 2-substituted trifluoromethylquinolines for the evaluation of
      leishmanicidal activity.
AB  - The synthesis of 2-substituted-trifluoromethylquinolines from aniline,
      trifluoromethylanilines, 3-aminoquinoline and trifluoromethylquinaldines is
      reported. In vitro antileishmanial evaluation of 2-alkyl, 2-alkenyl and 2
      epoxypropyl-trifluoromethylquinolines is presented.

PMID- 11310680
TI  - A novel antivirally active fucan sulfate derived from an edible brown alga,
      Sargassum horneri.
AB  - A novel fucan sulfate (Hor-1) was isolated from the hot water extract of an
      edible brown alga, Sargassum horneri (Turner) C. Agardh. The fucan sulfate was
      revealed to have sugar linkage types, sulfate content and uronic acid content
      different from those of sodium hornan (Na-HOR), another fucan sulfate isolated
      from this alga. However, it exhibited inhibitory activity against replication of
      herpes simplex virus type 1 with similar potency to Na-HOR.

PMID- 11310681
TI  - Revised structure of cercidinin A, a novel ellagitannin having (R)
      hexahydroxydiphenoyl esters at the 3,4-positions of glucopyranose.
AB  - The structure of cercidinin A, an ellagitannin isolated from the bark of
      Cercidiphyllum japonicum, was revised to 1,2,6-tri-O-galloyl-3,4-(R)
      hexahydroxydiphenoyl-beta-D-glucose by two-dimensional NMR spectral analysis.
      Cercidinin A represents the first ellagitannin possessing a hexahydroxydiphenoyl
      group at the 3,4-positions of a modified 4C1-glucopyranose core.

PMID- 11310682
TI  - Amino acids and peptides. XXXVIII. Facile synthesis of laminin-related peptide
      poly(ethylene glycol) hybrids by the solid phase method.
AB  - Poly(ethylene glycol) (PEG) has been studied as a drug-carrier for proteins, but
      not for small peptides. Laminin, a cell adhesive protein, has Tyr-Ile-Gly-Ser-Arg
      (YIGSR) sequence and peptides containing this sequence inhibit experimental
      metastasis. We have studied PEG hybrids of YIGSR and other small laminin-related
      peptides. In a previous paper, we reported preparation of YIGSR-PEG hybrids by
      combination of the solid phase method and the solution method, but the synthetic
      procedure was problematic. Here we report a facile synthesis of PEG hybrids of
      YIGSR (PEG-YIGSR, YIGSR-PEG, PEG-YIGSR-PEG) by the solid phase method.

PMID- 11310683
TI  - Studies on the constituents of Broussonetia species VIII. Four new pyrrolidine
      alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid,
      broussonetine U, from Broussonetia kazinoki Sieb.
AB  - Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline
      alkaloid, broussonetine U were isolated from the branches of Broussonetia
      kazinoki SIEB. (Moraceae) in low yield. Broussonetines R, S and T were formulated
      as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R)-1-hydroxy-3-[6-(4
      hydroxybutyl)-cyclohexy-2-on-1(6)-enyllpropyl] pyrrolidine (1), (2R,3R,4R,5R)-2
      hydroxymethyl-3,4-dihydroxy-5-[(1R,10S)-1,10,13-trihydroxytridecyl] pyrrolidine
      (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,5S)-1,5, 13-trihydroxy-10
      oxo-tridecyl] pyrrolidine (3). And broussonetines U and V were proposed to be
      (2S,3S,4S)-2-hydroxymethyl-3, 4-dihydroxy-5-(9-oxo-13-hydroxytridecyl)-5
      pyrroline (4), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)-9-oxo-13
      hydroxy-3-tridecenyl] pyrrolidine (5), respectively, by spectroscopic and
      chemical methods.

PMID- 11310684
TI  - Cycloaddition of 2(1H)-pyridones having a methoxycarbonyl group to 1,3-butadiene
      derivatives.
AB  - The cycloaddition of 4-methoxycarbonyl-2(1H)-pyridones to silyloxydienes gave
      isoquinolone derivatives in reasonable yields. Furthermore, the cycloaddition of
      6-methoxycarbonyl-2(1H)-pyridones to 2,3-dimethyl-1,3-butadiene produced
      cycloadducts (isoquinolone and quinolone derivatives) and double cycloadducts
      (phenanthridone derivatives). The activation energies using Gaussian 98 with
      RHF/3-21G level of 4- and 6-methoxycarbonyl-2(1H)-pyridones coincided with the
      experimental facts.

PMID- 11310685
TI  - Novel retinoidal tropolone derivatives. Bioisosteric relationship of tropolone
      ring with benzoic acid moiety in retinoid structure.
AB  - Several tropolone derivatives (4-7) were designed as novel retinoids on the
      assumption that the tropolone ring may mimic the benzoic acid moiety in retinoid
      structures, such as Am80 (2). Among the synthesized compounds, 5-[2-(5,6,7,8
      tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethynyl]tropolone (7a) showed moderate
      potency as a differentiation-inducer of HL-60 cells. The activities of the
      tropolones were greatly enhanced in the presence of HX630, an RXR agonist
      (retinoid synergist).

PMID- 11310686
TI  - The biosynthesis of broussonetines: origin of the carbon skeleton.
AB  - Broussonetines are glycosidase-inhibitory alkaloids obtained from Broussonetia
      kazinoki. Feeding experiments using [1-13C]glucose and 13C-NMR spectroscopic
      studies showed that broussonetines are biosynthesized through routes similar to
      those of sphingosine and phytosphingosine.

PMID- 11310687
TI  - The first example for cycloenantiomeric hexahomooxacali.
AB  - Cycloenantiomeric hexahomooxacalix[3]arenes with different substituents on the
      three upper rims were synthesized for the first time by fixing their conformation
      into a cone. A cycloenantiomeric hexahomooxacalix[3]arene 6 was resolved into
      both enantiomeric forms and chiroptically characterized. Preliminary 1H-NMR
      studies indicated that the optically resolved cycloenantiomer 6 could
      discriminate the enantiomers of hydrochloride of phenylalanine ethyl ester.

PMID- 11310688
TI  - Nosocomial infection rates in an Italian intensive care unit using the national
      nosocomial infection surveillance system.

PMID- 11310689
TI  - Frequency of intravenous administration set changes and bacteremia: defining the
      risk.

PMID- 11310690
TI  - Optimal frequency of changing intravenous administration sets: is it safe to
      prolong use beyond 72 hours?
AB  - OBJECTIVE: To determine the safety and cost-effectiveness of replacing the
      intravenous (IV) tubing sets in hospitalized patients at 4- to 7-day intervals
      instead of every 72 hours. DESIGN: Prospective, randomized study of infusion
      related contamination associated with changing IV tubing sets within 3 days
      versus within 4 to 7 days of placement. SETTING: A tertiary university cancer
      center. PATIENTS AND METHODS: Cancer patients requiring IV infusion therapy were
      randomized to have the IV tubing sets replaced within 3 days (280 patients) or
      within 4 to 7 days of placement (232 patients). Demographic, microbiological, and
      infusion-related data were collected for all participants. The main outcome
      measures were infusion- or catheter-related contamination or colonization of IV
      tubing, determined by quantitative cultures of the infusate, and infusion- or
      catheter-related bloodstream infection (BSI), determined by quantitative culture
      of the infusate in association with blood cultures in febrile patients. RESULTS:
      The two groups were comparable in terms of patient and catheter characteristics
      and the agents given through the IV tubing. Intent-to-treat analysis demonstrated
      a higher level of tubing colonization in the 4- to 7-day group versus the 3-day
      group (median, 145 vs 50 colony-forming units; P=.02). In addition, there were
      three episodes of possible infusion-related BSIs, all of which occurred in the 4-
      to 7-day group (P=.09). However, when the 84 patients who received total
      parenteral nutrition, blood transfusions, or interleukin-2 through the IV tubing
      were excluded, the two groups had a comparable rate of colonization (0.4% vs
      0.5%), with no catheter- or infusion-related BSIs in either group. CONCLUSION: In
      patients at low risk for infection from infusion- or catheter-related infection
      who are not receiving total parenteral nutrition, blood transfusions, or
      interleukin-2, delaying the replacement of IV tubing up to 7 days may be safe, as
      well as cost-effective

PMID- 11310691
TI  - A hospital epidemic of vancomycin-resistant Enterococcus: risk factors and
      control.
AB  - OBJECTIVE: To determine risk factors for vancomycin-resistant Enterococcus (VRE)
      colonization during a hospital outbreak and to evaluate Centers for Disease
      Control and Prevention (CDC)-recommended control measures. DESIGN:
      Epidemiological study involving prospective identification of colonization and a
      case-control study. SETTING: A university hospital. PARTICIPANTS: Patients on
      eight wards involved in outbreak from late 1994 through early 1995. METHODS:
      Cases were matched by ward and culture date with up to two controls. Risk factors
      were evaluated with four multivariate models using conditional logistic
      regression. The first evaluated proximity to other VRE patients and isolation
      status. The second evaluated proximity to unisolated VRE cases and three
      variables independently predictive after adjustment for proximity. The third
      evaluated seven significant univariate predictors in addition to proximity to
      unisolated VRE in backward, stepwise logistic regression. The fourth assessed
      proximity to VRE with all other variables collected, clustered in a principal
      components analysis. Pulsed-field gel electrophoresis was performed to assess
      clonality of two outbreak strains. RESULTS: The incidence of transmission
      declined significantly after CDC guidelines were implemented. Proximity to
      unisolated VRE cases during the prior week was a significant predictor of
      acquisition in each of four multivariate models. Other significant risk factors
      in multivariate models included a history of major trauma and treatment with
      metronidazole. Pulsed-field gel electrophoresis confirmed the clonality of two
      outbreak strains. CONCLUSIONS: VRE was transmitted between patients during a
      hospital epidemic, with proximity to previously unisolated VRE patients being an
      important risk factor. Weekly surveillance cultures and contact isolation of
      colonized patients significantly reduced spread

PMID- 11310692
TI  - Nosocomial colonization of premature babies with Klebsiella oxytoca: probable
      role of enteral feeding procedure in transmission and control of the outbreak
      with the use of gloves.
AB  - OBJECTIVE: To investigate the persistence of colonization of premature babies by
      Klebsiella oxytoca, with special emphasis on the mode of transmission of the
      bacterium and evaluation of Standard Precautions to stop the epidemic. DESIGN:
      Retrospective analysis of cases and prospective study of systematic
      bacteriological samples (stools and throat) from babies, healthcare workers
      (HCWs), and environment, with genotyping of strains by arbitrarily primed
      polymerase chain reaction. SETTING: A premature baby unit (PBU) and a neonatal
      intensive care unit in the university hospital of Saint-Etienne, France. RESULTS:
      An outbreak of K oxytoca was suspected in two pediatric wards after the
      occurrence of a fatal bacteremia in a newborn hospitalized in the PBU and the
      colonization of other babies 2 months later. Retrospective analysis showed that
      24 babies' digestive tract had been colonized. No environmental reservoir was
      recovered in the units nor in enteral feeding. No K oxytoca was isolated from HCW
      samples. Genotyping confirmed the presence of epidemic strains, although
      independent clones were responsible for infections or colonizations in each of
      the two units. The chronology and the site of babies' colonization (isolation of
      K oxytoca in stools before throat) were determined during a prospective study and
      suggested that enteral feeding procedures could be the source of contamination.
      Therefore, use of gloves during this practice by HCWs was recommended and, after
      readjustment of Standard Precautions, stopped the outbreak. CONCLUSION: To
      prevent cross-contamination among high-risk babies, careful attention must be
      paid to Standard Precautions. Bacteriological surveillance of the digestive tract
      of neonates could help to check compliance with these guidelines

PMID- 11310693
TI  - A blinded comparison of three laboratory protocols for the identification of
      patients colonized with methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: To compare three laboratory screening protocols for the detection of
      methicillin-resistant Staphylococcus aureus (MRSA) from surveillance specimens
      (mannitol-salt agar containing 2 microg/mL of oxacillin [MSA-2], mannitol-salt
      agar containing 4 microg/mL of oxacillin [MSA-4], and a broth-containing protocol
      as recommended by the American Society for Microbiology [M-ASM]). DESIGN: Blinded
      comparative laboratory study and cost analysis. SETTING: University-affiliated
      microbiology laboratory. METHODS: Outcome measurements included rate of detection
      of MRSA-positive specimens and patients, turnaround time, and media and
      technologist costs. All MRSA culture swabs obtained from any patient site from
      November 1998 to April 1999 were included. RESULTS: The M-ASM protocol detected
      between 19.1% and 32.0% more MRSA-positive specimens and between 13.3% and 23.3%
      more MRSA-positive patients per surveillance event than the MSA-4 and MSA-2
      protocols, respectively. There was no difference in positive-culture reporting
      time between the M-ASM and MSA4 protocols. The broth-containing protocol was 2-
      to 2.5-fold more expensive than the simpler protocols, taking into account media
      and laboratory personnel costs. CONCLUSIONS: It remains to be determined whether
      it is cost beneficial for a hospital to adopt the M-ASM, as the potential cost of
      MRSA transmission from unidentified MRSA-colonized patients is unknown. A broth
      containing protocol should be considered the gold standard in future studies
      examining newer MRSA screening protocols

PMID- 11310694
TI  - Surveillance of nosocomial infections in ICUs: is postdischarge surveillance
      indispensable?
AB  - OBJECTIVE: To determine how many infections are missed if the postdischarge
      surveillance (PDS) follow-up of intensive care unit (ICU) patients that is
      required by the National Nosocomial Infection Surveillance System method is not
      done. DESIGN: ICU patients were followed up and surveillance results with PDS
      (gold standard) and without PDS were compared. SETTING: Surgical or
      interdisciplinary ICUs in eight German acute-care hospitals. PATIENTS: All 1,857
      patients within a 6-month period in the participating ICUs (a total of 9,129 ICU
      patient-days). RESULTS: Without PDS, 45 urinary tract infections (UTIs) were
      diagnosed, compared with 53 with PDS; thus, 15% of the UTIs were missed if no
      postdischarge follow-up was performed. Three nosocomial pneumonias (4%) and one
      bloodstream infection (8%) also were missed if surveillance was carried out
      without PDS. A total of 198 nosocomial infections (NIs) were recorded with PDS,
      compared to 175 NIs without PDS. Approximately 12% of all ICU-associated NIs were
      missed if no follow-up was done. CONCLUSIONS: Since it is very time-consuming to
      follow patients after their transfer from the ICU, we do not perform a
      postdischarge follow-up of patients in the course of routine surveillance.

PMID- 11310695
TI  - Laboratory-based surveillance for vancomycin-resistant enterococci: utility of
      screening stool specimens submitted for Clostridium difficile toxin assay.
AB  - OBJECTIVE: To study vancomycin-resistant enterococci (VRE) gastrointestinal
      colonization prevalence in high-risk hospitalized patients and to assess the cost
      and utility of this laboratory-based surveillance. SETTING: Large university
      teaching hospital. DESIGN: Quarterly prevalence culture survey of 50 stool
      specimens submitted for Clostridium difficile toxin A assay from October 1996
      through June 1999 (n=526). Screening culture survey of all C difficile-positive
      stool specimens from July 1998 through June 1999 (n=140). PATIENTS: Specimens for
      analysis were collected from patients who were admitted to the hospital and who
      had C difficile toxin A testing ordered. Patient samples were excluded from
      analysis if they were obtained from patients not hospitalized at UCLA Medical
      Center, if the C difficile toxin assay result was indeterminate, or if the
      patient was known to have previous VRE colonization or infection. RESULTS: During
      quarterly surveillance, VRE was detected in 19.8%, C difficile toxin A in 9.5%,
      and both VRE and C difficile toxin A in 3.2% of stool specimens submitted for C
      difficile toxin assay. Patients whose stool specimens were positive for C
      difficile toxin A were significantly more likely than those whose specimens were
      negative to have VRE detected (odds ratio, 2.3; 95% confidence interval, 1.2
      4.5). Based on these findings, in July 1998, we began routine screening of all C
      difficile-positive stool specimens for VRE. From July 1998 through June 1999, 58
      (41.4%) of 140 patients with C difficile-positive specimens had VRE newly
      detected in the stool. The combined cost of the two laboratory-based surveillance
      strategies was approximately $62 per VRE-positive patient identified and $5,800
      per year. CONCLUSION: Quarterly surveillance of stool submitted for C difficile
      assay combined with screening all C difficile-positive stools is a cost-effective
      and efficient strategy for detecting VRE stool colonization among high-risk
      hospitalized patients. Such a laboratory-based surveillance should be included as
      part of a comprehensive program to limit nosocomial VRE transmission.

PMID- 11310696
TI  - Blood products: a significant risk factor for long-term catheter-related
      bloodstream infections in cancer patients.
AB  - Data obtained from a previous prospective randomized study in cancer patients
      conducted at our institution were analyzed to investigate risk factors for
      catheter-related (CR) bloodstream infections (BSIs). Our recent analysis showed
      that the administration of blood products through central venous catheters was a
      risk factor for CR BSI, whereas thrombocytopenia during catheterization may have
      provided protection against CR BSI, as did central venous catheter insertion
      under maximal sterile barrier precautions

PMID- 11310697
TI  - Urinary tract infections in long-term-care facilities.
AB  - Urinary tract infection (UTI) is the most common bacterial infection occurring in
      residents of long-term-care facilities. It is a frequent reason for antimicrobial
      administration, but antimicrobial use for treating UTIs is often inappropriate.
      Achieving optimal management of UTI in this population is problematic because of
      the very high prevalence of bacteriuria, evidence that the treatment of
      asymptomatic bacteriuria is not beneficial, and the clinical and microbiological
      imprecision in diagnosing symptomatic UTI. This position paper has been
      developed, using available evidence, to assist facilities and healthcare
      professionals in managing this common problem.

PMID- 11310698
TI  - Reality check: should we use vancomycin for the prophylaxis of intravascular
      catheter-associated infections?
AB  - The use of intravascular catheters is associated with increased risk of
      bloodstream infections, principally caused by coagulase-negative staphylococci.
      This "Reality Check" session, held at the 4th Decennial International Conference
      on Nosocomial and Healthcare-Associated Infections, focused on the question of
      whether, and in what manner, vancomycin should be used for the prophylaxis of
      these infections

PMID- 11310699
TI  - OSHA revises bloodborne pathogen standard--mandates sharps safety devices.

PMID- 11310700
TI  - US action plan to combat antimicrobial resistance.

PMID- 11310701
TI  - Double-cystotome capsulorhexis technique in pediatric cataracts.

PMID- 11310702
TI  - Late presentation of orbital roof blow-out fracture.

PMID- 11310703
TI  - Adjunctive use of alpha-chymotrypsin during infantile lensectomy and vitrectomy.

PMID- 11310704
TI  - Pseudo-Brown's syndrome secondary to a growing conjunctival dermolipoma.

PMID- 11310705
TI  - Ocular involvement in siblings with familial mediterranean fever.

PMID- 11310706
TI  - Rufous albinism.

PMID- 11310707
TI  - Topical anesthesia for strabismus surgery.

PMID- 11310708
TI  - Visual acuities after levodopa administration in amblyopia.
AB  - PURPOSE: To investigate the effect of the augmentation of levodopa with part-time
      and full-time occlusion on visual acuity and to determine its late results in
      amblyopia. METHODS: Seventy-two patients with amblyopia were prospectively
      studied and randomly distributed into groups A, B, and C consisting of 24
      patients each. Group A patients received levodopa alone, group B received
      levodopa and part-time (3 hours/day) occlusion, and group C received levodopa and
      full-time (during all waking hours) occlusion of the dominant eye. Levodopa 0.50
      mg/kg body weight, with a 25% fixed dose combination of carbidopa, was
      administered orally three times a day for 7 weeks. Snellen visual acuity and its
      logMAR equivalent were recorded before treatment, at weeks 1, 3, 5, and 7 after
      starting treatment, and every 6 weeks for 1 year after the completion of
      treatment. RESULTS: Fifty-three (74%) of the 72 patients had an improvement in
      visual acuity after treatment. Forty-four of the 53 patients with improved visual
      acuities completed 1-year post-treatment follow-up. Twenty-three (52%) of the 44
      patients had a regression in visual acuity. CONCLUSION: The augmentation of
      levodopa with part-time or full-time occlusion does not enhance the recovery of
      vision in amblyopia. Improved visual acuity after levodopa administration
      persists at least 1 year in almost half of patients after cessation of treatment.
      Addition of full-time occlusion to levodopa helps maintain improved visual acuity
      for a longer duration compared to levodopa alone or combined with part-time
      occlusion.

PMID- 11310709
TI  - Effect of botulinum toxin A chemodenervation in sensory strabismus.
AB  - PURPOSE: To study the effect of botulinum toxin type A chemodenervation in
      sensory strabismus. METHODS: Twelve patients with sensory strabismus were treated
      with an injection of botulinum toxin type A (Botox; Allergan, Irvine, Calif).
      Botulinum toxin type A was diluted with 0.9% sodium chloride without preservative
      at a dose that ranged from 1.25-5 U. A Teflon-coated needle electrode was
      inserted into the medial rectus muscle in cases of esotropia and into the lateral
      rectus muscle in cases of exotropia. Four patients were treated with > or =2
      injections of botulinum toxin type A. Changes in the angle of strabismus and
      related complications were followed for >6 months postinjection. RESULTS: The
      mean deviation before injection was 33.8 prism diopters (delta) and the mean
      corrective effect on the deviation was 72.8% after injection in patients with
      sensory strabismus. The final deviation in 9 patients was <10 delta.
      Complications were hypertropia in 3 (25%) patients and conjunctival hemorrhage in
      1 (8.3%) patient. CONCLUSION: Botulinum toxin type A is likely to prevent muscle
      contracture and affect muscle and neuronal tissues. This study on the effects of
      sensory strabismus with botulinum toxin type A injection suggests it has the
      potential to replace surgery or be used as an adjuvant therapy.

PMID- 11310710
TI  - Open globe injuries in children: a retrospective analysis.
AB  - PURPOSE: To study the outcome of open globe injuries in patients aged <14 years
      and compare the results between patients who presented approximately 30 years ago
      and a recent series. METHODS: Between January 1970 and January 1993, 180 eyes of
      children who presented with an open globe injury were retrospectively analyzed.
      Patients were divided into two groups. One group of children underwent treatment
      of an open globe injury between January 1970 and December 1981 (group A) and
      another between December 1985 and January 1993 (group B). Main outcome measures
      studied were final visual acuity and enucleation rates. Risk factors studied
      included age, race, sex, visual acuity, type of trauma, and various injury
      characteristics at presentation. RESULTS: The factors associated with visual
      outcomes included: age, type of injury, wound size, initial visual acuity, and
      retinal detachment. Final visual outcome and enucleation rates were not
      significantly different between the older series (group A) and the recent series
      (group B). Lenticular damage, location, posterior extent of the injury, and
      presence of an intraocular foreign body had been significant prognostic factors
      in the older series, but were not statistically associated with the prognosis in
      the recent series. CONCLUSION: The nature of the injury and the patient's age are
      the main determining factors in the outcome of open globe injuries in children.

PMID- 11310711
TI  - Heredity versus abnormalities in pregnancy and delivery as risk factors for
      different types of comitant strabismus.
AB  - PURPOSE: To elucidate risk factors for different types of comitant strabismus,
      the incidence of heredity and abnormalities in pregnancy and delivery was
      compared among different types of strabismus. METHODS: Between May 1998 and
      January 1999, a prospective clinical study of 500 consecutive patients with
      comitant strabismus at a referral-based university hospital was performed using
      data collected from questionnaires and interviews. Inclusion criteria were
      infantile esotropia (168 patients), accommodative and partially accommodative
      esotropia (97 patients), microesotropia (15 patients), acquired esotropia (12
      patients), intermittent or constant exotropia (205 patients), and congenital
      exotropia (3 patients). Exclusion criteria were strabismus associated with
      systemic and central nervous system abnormalities and organic eye diseases.
      RESULTS: Family history was significantly more prevalent in intermittent or
      constant exotropia and accommodative or partially accommodative esotropia than in
      infantile esotropia (P<.0001 and P=.0267, respectively, Fisher's exact test). In
      contrast, abnormalities in pregnancy and delivery were noted at a significantly
      higher rate in infantile esotropia than in accommodative or partially
      accommodative and in intermittent or constant exotropia (P=.003 and P=.0215,
      respectively). Patients with infantile esotropia were significantly younger at
      the survey than those with the other two types of strabismus (P=.0004 and
      P<.0001). No significant difference was found in the number of siblings,
      birthweight, maternal age at delivery, or maternal cigarette smoking or alcohol
      drinking among these three types of strabismus. CONCLUSION: Heredity and
      abnormalities in pregnancy and delivery are two major risk factors for comitant
      strabismus and contribute at different levels to the development of infantile
      esotropia, accommodative or partially accommodative esotropia, and intermittent
      or constant exotropia.

PMID- 11310712
TI  - Effect of late surgery for acquired esotropia on visual evoked potential.
AB  - PURPOSE: To asses the effect of strabismus surgery on visual evoked potential
      (VEP) amplitude after age 5 years in children with acquired esotropia. METHODS:
      Visual evoked potentials to binocular and monocular pattern reversal stimulation
      were recorded in 10 children aged 5 to 6 years before and 3 months after surgical
      correction of their esotropia. Visual function (fusion) was tested by
      synoptophore after strabismus surgery. Electrophysiological and clinical data
      were correlated following surgical intervention. RESULTS: A significant increase
      in pattern VEP amplitudes was noted following strabismus surgery. Visual evoked
      potential changes were most prominent on binocular stimulation. Binocular fusion
      showed similarly significant improvement after intervention. Postoperative VEP
      data, however, were not consistently correlated with functional improvement.
      CONCLUSION: Surgical intervention in esotropia, even if performed years beyond
      the end of the classical critical period, can have a strong effect on binocular
      VEPs and a beneficial effect on the development of binocular fusion.

PMID- 11310713
TI  - Checklist for the evaluation of low vision in uncooperative patients.
AB  - PURPOSE: To present a checklist for the evaluation of low vision in uncooperative
      patients; in this specific case, children with neurological deficits. METHOD: The
      checklist includes several behavioral indicators obtainable with a standard
      clinical examination. Each test is assigned a score (0=failure, 1=success). The
      final visual quotient score is obtained by dividing the partial score by the
      total number of tests performed. Eleven children with cerebral visual impairment
      were studied using behavioral and preferential looking techniques. RESULTS:
      Visual quotient was >0 in all patients, indicating that residual visual function
      was always detectable. Average visual quotient was 0.74. CONCLUSION: Visual
      quotient can be useful both for follow-up examinations and comparison and
      integration with other evaluation methods (behavioral and instrumental) of
      residual visual capacity. In particular, if combined with preferential looking
      techniques, visual quotient testing permits characterization of the entire
      spectrum of low vision.

PMID- 11310714
TI  - Medial rectus muscle laceration.

PMID- 11310715
TI  - Asthma in children: are chlamydia or mycoplasma involved?
AB  - Asthma aetiology is complex, involving interactions between genetic
      susceptibility, allergen exposure and external aggravating factors such as air
      pollution, smoking and respiratory tract infections. Available evidence supports
      a role for acute Chlaymdia pneumoniae or Mycoplasma pneumoniae respiratory tract
      infection as a trigger for 5 to 30% of wheezing episodes and asthma
      exacerbations. It also appears that acute infections with C. pneumoniae and M.
      pneumoniae can initiate asthma in some previously asymptomatic patients; however,
      the quantitative role for these atypical bacteria as asthma initiators is unknown
      at the present time. Whether chronic infections with these agents play an
      important role in persistent asthma symptoms and/or to asthma severity is unclear
      and additional information should be acquired before definite conclusions can be
      reached. Improvement in asthma symptoms after antimicrobial therapy active
      against C. pneumoniae and M. pneumoniae has been observed. In some studies C.
      pneumoniae seems to be more important for asthma pathogenesis and exacerbations
      than M. pneumoniae; in other reports the role of M. pneumoniae appears to be more
      significant. However, a number of questions remain unanswered. Carefully
      controlled randomised trials are clearly warranted to determine whether infection
      with atypical bacteria is really associated with asthma and to define the
      appropriate role of antimicrobial treatment.

PMID- 11310716
TI  - Aetiology and management of children with acute fever of unknown origin.
AB  - This is part I of a 2-part paper on fever of unknown origin (FUO) in children.
      FUO is best defined as fever without obvious source on initial clinical
      examination and then classified into acute (illness of < or =1 week's duration)
      and prolonged (>7 to 10 days' duration). Aetiologically, there is a marked
      overlap between acute and prolonged FUO, and infections are major players in
      both. Age, climate, local epidemiology and host factors are the major
      aetiological factors that should be considered in the choice of definitive tests.
      Depending on age, serious bacterial infections (including bacteraemia, meningitis
      and urinary tract infection) occur in 3 to 20% of cases of acute FUO. Prevention
      of mortality and sequelae from these infections, particularly bacteraemia and
      meningitis, is of particular concern in acute FUO. An individualised approach,
      based on clinical evaluation supplemented with screening and definitive
      laboratory tests to determine the need for empiric antibiotic therapy and
      hospitalisation, seems to be the best approach to acute FUO (although this may be
      less applicable to neonates and infants younger than 90 days, particularly those
      aged 0 to 7 days). The place of laboratory tests, empiric antibiotic therapy and
      hospitalisation are important issues that are likely to remain so for some time.

PMID- 11310717
TI  - Haemopoietic growth factors in paediatric oncology: a review of the literature.
AB  - Recombinant haemopoietic growth factors (HGFs) are an attractive adjunct to
      reduce morbidity from chemotherapy regimens and their use has become widespread
      in paediatric oncology. Although patients receiving HGFs often have faster
      haematological recovery after intensive chemotherapy, this does not always
      translate into meaningful clinical benefits. This article reviews the clinical
      effectiveness of HGFs in a variety of different contexts. Most published studies
      have used granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage
      colony-stimulating factor (GM-CSF) as prophylaxis to ameliorate the subsequent
      neutropenia following intensive chemotherapy. These 2 agents have also been used
      to mobilise peripheral blood stem cells for autologous transplantation. HGFs
      specific for anaemia and thrombocytopenia are currently in paediatric clinical
      trials and it is hoped that the proper context and administration strategy can be
      found to make their use clinically effective. This article also reviews data on
      toxicity, specifically focusing on differences between various formulations of
      growth factors. HGFs are expensive, and cost-benefit analyses reviewed in this
      article give an important perspective on the financial aspects of paediatric
      cancer care. Because HGFs do not benefit every child receiving chemotherapy and
      overuse increases costs and may result in unnecessary adverse effects, evidence
      based guidelines for their rational use in paediatric oncology are proposed.

PMID- 11310718
TI  - Urinary tract infections in children younger than 5 years of age: epidemiology,
      diagnosis, treatment, outcomes and prevention.
AB  - Although the true incidence of urinary tract infections (UTIs) in children is
      difficult to estimate, they are one of the most common bacterial infections seen
      by clinicians who care for young children. Except for the first 8 to 12 weeks of
      life, when infection of the urinary tact may be secondary to a haematogenous
      source, UTI is believed to arise by the ascending route after entry of bacteria
      via the urethra. Enterobacteriaceae are the most common organisms isolated from
      uncomplicated UTI. Infection with Staphylococcus aureus is rare in children
      without in-dwelling catheters or other sources of infection, and coagulase
      negative staphylococci and Candida spp. are associated with infections after
      instrumentation of the urinary tract. The diagnosis of UTI in young children is
      important as it is a marker for urinary tract abnormalities and, in the newborn,
      may be associated with bacteraemia. Early diagnosis is critical to preserve renal
      function of the growing kidney. A urine specimen for culture is necessary to
      document a UTI in a young child. Prior to culture, urinalysis may be useful to
      detect findings supporting a presumptive diagnosis of UTI. The goals of the
      management of UTI in a young child are: (i) prompt diagnosis of concomitant
      bacteraemia or meningitis, particularly in the infant; (ii) prevention of
      progressive renal disease by prompt eradication of the bacterial pathogen,
      identification of abnormalities of the urinary tract and prevention of recurrent
      infections; and (iii) resolution of the acute symptoms of the infection. Delay in
      initiation of the antibacterial therapy is associated with an increased risk of
      renal scarring. The initial choice of antibacterial therapy is based on the
      knowledge of the predominant pathogens in the patient's age group, antibacterial
      sensitivity patterns in the practice area, the clinical status of the patient and
      the opportunity for close follow-up. Imaging studies to detect congenital or
      acquired abnormalities are recommended following the first UTI in all children
      aged <6 years. Patients with significant urinary tract abnormalities and/or
      frequent symptomatic UTI may benefit from prophylactic antibacterials. The main
      long term consequence of UTI is renal scarring which may lead to hypertension and
      end-stage renal disease. Prevention of recurrent UTI focuses on detection, and
      correction if possible, of urinary tract abnormalities. Interventions that have
      been associated with a decrease in symptomatic UTI in children with a history of
      recurrent UTI include relief of constipation and voiding dysfunction.

PMID- 11310720
TI  - A comparison of African American and White American veteran MMPI-2 profiles.
AB  - The present study compared a matched sample of 180 African American and 180 White
      American veterans who completed the MMPI-2 as a part of their evaluation while
      receiving inpatient psychiatric treatment. Findings indicated no significant
      multivariate or univariate effects associated with race on the basic validity and
      clinical scales, a significant multivariate effect but no significant univariate
      effects associated with race across the supplementary scales. Overall the two
      groups had very similar mean profiles across the basic validity, clinical, and
      supplementary scales. Comparison of the two groups on the content scales yielded
      a significant multivariate and significant univariate effects with African
      Americans scoring higher on the FRS, BIZ, CYN, and ASP scales. Because the two
      groups differed in terms of frequency and type of drug abuse, follow-up 2 x 2
      univariate analyses of variance were conducted for the FRS, BIZ, CYN, and ASP
      content scales comparing participants classified in terms of presence or absence
      of a primary or secondary drug abuse diagnosis by race. A significant main effect
      associated with drug abuse was obtained for ASP. Results are discussed and
      considered in light of earlier research on the MMPI-2 and race. Content scale
      differences are also discussed in terms of possible differences in worldview.

PMID- 11310721
TI  - An evaluation of the effects of Rorschach EB style on the diagnostic utility of
      the Depression Index.
AB  - Several empirical studies have found the Rorschach Depression Index (DEPI) to
      have questionable diagnostic utility. Studies using adolescent samples suggest
      that the DEPI has limited sensitivity and fails to differentiate effectively
      between adolescents with and without depression diagnoses. The present study was
      conducted to evaluate Viglione, Brager, and Haller's suggestion that the DEPI may
      have better discriminative ability for individuals with extratensive problem
      solving styles, measured by the Rorschach EB (Erlebnistypus) variable, compared
      to those with introversive and ambitent styles. Comparisons were conducted
      between adolescents with depression-related diagnoses and adolescents with other
      diagnoses for each of the three EB groups. The results failed to support the
      hypothesized greater discriminative power of DEPI for depressed extratensives,
      and suggest caution in using the DEPI to evaluate adolescent depression.

PMID- 11310719
TI  - Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension
      for the treatment of influenza in children.
AB  - OBJECTIVE: Oseltamivir (Ro 64-0796) is an ester prodrug of the active metabolite
      Ro 64-0802 (oseltamivir carboxylate), a potent and selective inhibitor of the
      neuraminidase enzyme of influenza virus. In this study we report the
      pharmacokinetics of oseltamivir in healthy children volunteers (study 1) and in
      children with influenza (study 2). STUDY PARTICIPANTS AND METHODS: In study 1, an
      open-label, single dose study, serial plasma samples were obtained from a total
      of 18 healthy children (5 to 18 years) who were grouped by age (n = 6 per group)
      and received single oral doses of oseltamivir 2 mg/kg. In study 2, a randomised,
      placebo controlled phase III study in paediatric children (1 to 12 years)
      presenting with influenza symptoms, 199 pharmacokinetic sparse samples were
      obtained from 87 patients, and serial samples were obtained from 5 patients.
      Pooled data were compared with those from adult studies. RESULTS: Children (1 to
      12 years) eliminated the active metabolite faster than both adolescents (13 to 18
      years) and adults, resulting in lower exposure to the active drug. In these
      children, oseltamivir 2 mg/kg twice daily resulted in drug exposures within the
      range associated with tolerability and efficacy in adults administered
      approximately 1 mg/kg twice daily. Unit doses of oseltamivir 30, 45 and 60mg oral
      suspension are recommended twice daily in children weighing < or =15 kg (or < or
      =33 lb, aged 1 to 3 years), > 15 to 23 kg (or >33 to 51 lb, aged 4 to 7 years)
      and >23 to 40 kg (or >51 to 88 lb, aged 8 to 12 years), respectively. A 75 mg
      capsule may be a viable dosage formulation in children (e.g. over 8 years of age)
      who are able to swallow solid dosage forms. CONCLUSIONS: Young children cleared
      the active metabolite oseltamivir carboxylate at a faster rate than older
      children and adults. Convenient administration recommendations for the
      oseltamivir oral suspension in children are possible to maintain drug exposure
      within the target window.

PMID- 11310722
TI  - Confirmatory factor analysis of the Kaufman Adolescent and Adult Intelligence
      Test with young adolescents.
AB  - This study examined the factor structure of the Kaufman Adolescent and Adult
      Intelligence Test (KAIT) in 375 11- to 14-year-olds (normative sample) and 60
      sixth- and eighth-graders (cross-validation sample). Previous exploratory and
      confirmatory factor analyses of the KAIT have included optional subtests, which
      are often not administered in practice, and have not tested oblique versus
      orthogonal two-factor models. In this study, three factor models were tested via
      confirmatory factor analysis for the six core subtests of the KAIT: a one-factor
      general intelligence (g) model, an orthogonal fluid intelligence (Gf)
      crystallized intelligence (Gc) model, and an oblique Gf-Gc model. The orthogonal
      Gf-Gc model fit poorly in both samples. The g model fit only the cross-validation
      sample. The oblique Gf-Gc model fit both samples and fit significantly better
      than the g model in both samples. Additional tests of factor structure, path
      coefficients, and covariance between Gf and Gc indicated that the data from both
      samples fit even the most restrictive oblique Gf-Gc model tested. KAIT users can
      be confident that the Fluid and Crystallized IQs from the KAIT are adequate
      representations of a robust and interpretable factor structure when only the core
      subtests are administered to young adolescents.

PMID- 11310723
TI  - Cognitive complexity and the validity of clinicians' judgments.
AB  - Efforts to explain why some neuropsychologists are more accurate than others have
      been unsuccessful. In the present study, the relation between the cognitive
      complexity of clinicians and the validity of their judgments was investigated.
      Forty-two neuropsychologists completed a measure of cognitive complexity. The
      hypothesis that neuropsychologists who are high in cognitive complexity will be
      more accurate than those who are low in cognitive complexity was not supported.
      It is not clear why cognitive complexity was not significantly related to the
      validity of diagnostic ratings: One explanation is that the measure of cognitive
      complexity used in this study was inadequate but another possibility is that
      neuropsychologists who are low in cognitive complexity may still be able to
      achieve high levels of accuracy if they attend to normative data when they
      interpret test results.

PMID- 11310724
TI  - Self-report measures among transplant candidates: the impact of evaluative
      situations.
AB  - Experiment 1 was a between-subjects design comparing transplant candidates
      completing self-report measures under an evaluative versus an anonymous research
      condition. A cardiac disease group and a healthy community group served as
      controls. Transplant candidates in the anonymous research condition reported
      significantly more depression, anxiety, and negative affectivity as compared with
      transplant candidates in the evaluative condition and community controls. In
      contrast, the evaluative transplant group (a) did not differ from the community
      controls on any of the self-report measures, and (b) reported significantly less
      depression than cardiac disease controls. Experiment 2 was a within-subjects
      design with transplant candidates completing self-report measures under both an
      evaluative and an anonymous research condition. Significantly greater anxiety was
      reported under the anonymous research condition. Social desirability was
      significantly related to change in self-reported anxiety and depression across
      conditions, but was unrelated to change in endorsement of personality
      characteristics.

PMID- 11310725
TI  - The reliability and validity of a group-administered version of the body image
      assessment.
AB  - The Body Image Assessment (BIA) is a simple measure of body image disturbance.
      However, it has currently only been used with an individual administration format
      and only to assess ratings of current body size, ideal body size, and body
      dissatisfaction. It has also only been validated for use with women. In the
      current two studies, the reliability and validity of a group-administered version
      of the BIA procedure for both men and women that also assessed ratings of the
      ideal opposite sex and predictions about what the opposite sex would prefer as
      most attractive was examined. In the first study, results indicated good test
      retest reliability for the group version for current and ideal body size and good
      concurrent validity with the individual administration format of the BIA. The
      results of the second study supported the construct and predictive validity of
      the group administered BIA, suggesting that it is a time-efficient alternative to
      the original, individually administered assessment.

PMID- 11310726
TI  - Parenting alliance: a multifactor perspective.
AB  - The Parenting Alliance Measure (PAM) provides an operational representation of
      Weissman and Cohen's theory of parenting that has both clinical and research
      applications. The PAM is a 20-item, self-report instrument that measures the
      strength of the perceived alliance between parents of children ages 1 to 19
      years. Multigroup confirmatory factor analysis was used to examine whether the
      PAM measures the same constructs for mothers and fathers. In addition, a formal
      comparison between a one- and two-factor solution was conducted, and the
      invariance of parameter estimates for the preferred model was tested for mothers
      and fathers. Results indicated that the PAM measures the same dimensions for
      these two groups. A formal comparison between the one- and two-factor solutions
      favored the less parsimonious two-factor model. At the same time, the
      relationship between these constructs was sufficiently high to warrant
      interpretation of an overall parenting alliance score. Accordingly, results from
      the current investigation support two levels of interpretation on the PAM.
      Normative raw score conversions to percentile and standardized T scores are
      provided.

PMID- 11310727
TI  - Validity rates of the MMPI-2 and PAI in a rural inpatient psychiatric facility.
AB  - This study examines the validity rates of Minnesota Multiphasic Personality
      Inventory-2 (MMPI-2) and Personality Assessment Inventory (PAI) profiles in a
      rural inpatient population. The validity scales of 90 MMPI-2 and 90 PAI profiles
      were analyzed using published criteria for determining validity. Random
      responding, positive impression management, and negative impression management
      were also evaluated. The PAI had a higher number of valid profiles compared with
      the MMPI-2. Evidence suggests the primary source of the invalid profiles within
      the MMPI-2 is a higher level of endorsement of relatively rare statements. The
      substitution of the Infrequency-Psychopathology scale (Fp) for the Infrequency
      scale (F) on the MMPI-2 substantially reduced the number of invalid profiles.
      Contrary to expectations, the PAI did not demonstrate lower levels of invalid
      profiles due to random responding. Rates of invalid profiles for each scale are
      provided.

PMID- 11310728
TI  - Subtypes of clinical presentations in malingerers of posttraumatic stress
      disorder: an MMPI-2 cluster analysis.
AB  - This paper investigated subtypes of individuals trained and instructed to
      malinger Posttraumatic Stress Disorder (PTSD) through a cluster analysis of their
      Minnesota Multiphasic Personality Inventory-2 (MMPI-2) clinical and validity
      scales. Participants were 84 men and women college students at a community
      college in the southeastern United States. Two well fitting MMPI-2 cluster
      solutions were evaluated with discriminant analyses and multivariate analyses of
      variance (MANOVAs); a 2-cluster solution was deemed optimal. Significant between
      cluster differences emerged in follow-up analyses on most of the content scales
      of the MMPI-2. Most demographic variables did not account for differences in
      cluster membership. Clusters differed in their reported clarity of the materials
      used to educate them about PTSD. Discriminant analyses yielded better correct
      classification rates than those from previous studies, when the more severely
      symptomatic cluster was compared with a sample of clinical combat-related PTSD
      veterans. Implications are considered in conducting future malingered PTSD
      investigations.

PMID- 11310729
TI  - Concurrent validity of the Peabody Picture Vocabulary Test-Third Edition as an
      intelligence and achievement screener for low SES African American children.
AB  - Authors tested the validity of the Peabody Picture Vocabulary Test-Third Edition
      (PPVT-III) as a screening measure for intelligence and achievement. The PPVT-III
      and Kaufman Assessment Battery for Children (KABC) were administered to 416
      African American children of low socioeconomic status in a counterbalanced
      design. Results indicated that the PPVT-III correlated .58 with the KABC Mental
      Processing Composite (MPC) score; however, participants scored significantly
      lower (M = 8.3 points) on the PPVT-III than on the MPC. Although receiver
      operating characteristic (ROC) analyses supported the use of the PPVT-III as a
      valid intellectual and achievement screener, the selection of a single cutoff
      score for the PPVT-III was problematic. The purpose of the screening program
      should guide selection of a cutoff score for the PPVT-III.

PMID- 11310730
TI  - The validity of the Comprehensive Test of Nonverbal Intelligence as a measure of
      fluid intelligence.
AB  - The current investigation examined the validity of the Comprehensive Test of
      Nonverbal Intelligence (CTONI), an intelligence test that is purported to measure
      fluid intelligence. The CTONI was evaluated in comparison with the Kaufman
      Adolescent and Adult Intelligence Test (KAIT), an established measure of fluid
      and crystallized intelligence. Ninety-seven adults were administered these
      instruments in counterbalanced order. Results indicated that the sample's mean
      CTONI Nonverbal IQ (NIQ) deviated significantly from the mean KAIT Crystallized,
      Fluid, and Composite IQs. The CTONI mean NIQ underestimated KAIT Fluid and
      Composite IQs when individual participants were subdivided into existing KAIT
      ability categories and mean score comparisons were made. Results also indicated
      that the CTONI NIQ correlated strongly and positively with the KAIT Composite and
      Fluid IQs. Furthermore, the CTONI Geometric NIQ scale clearly demonstrated
      discriminant and convergent validity, whereas, the CTONI Pictorial NIQ (PNIQ) did
      not.

PMID- 11310731
TI  - Abnormal callose response phenotype and hypersusceptibility to Peronospoara
      parasitica in defence-compromised arabidopsis nim1-1 and salicylate hydroxylase
      expressing plants.
AB  - To investigate the impact of induced host defenses on the virulence of a
      compatible Peronospora parasitica strain on Arabidopsis thaliana, we examined
      growth and development of this pathogen in nim1-1 mutants and transgenic
      salicylate hydroxylase plants. These plants are unable to respond to or
      accumulate salicylic acid (SA), respectively, are defective in expression of
      systemic acquired resistance (SAR), and permit partial growth of some normally
      avirulent pathogens. We dissected the P. parasitica life cycle into nine stages
      and compared its progression through these stages in the defense-compromised
      hosts and in wild-type plants. NahG plants supported the greatest accumulation of
      pathogen biomass and conidiophore production, followed by nim1-1 and then wild
      type plants. Unlike the wild type, NahG and nim1-1 plants showed little induction
      of the SAR gene PR-1 after colonization with P parasitica, which is similar to
      our previous observations. We examined the frequency and morphology of callose
      deposits around parasite haustoria and found significant differences between the
      three hosts. NahG plants showed a lower fraction of haustoria surrounded by thick
      callose encasements and a much higher fraction of haustoria with callose limited
      to thin collars around haustorial necks compared to wild type, whereas nim1-1
      plants were intermediate between NahG and wild type. Chemical induction of SAR in
      plants colonized by P. parasitica converted the extrahaustorial callose phenotype
      in NahG to resemble closely the wild-type pattern, but had no effect on nim1-1
      plants. These results suggest that extrahaustorial callose deposition is
      influenced by the presence or lack of SA and that this response may be sensitive
      to the NIM1/NPR1 pathway. Additionally, the enhanced susceptibility displayed by
      nim1-1 and NahG plants shows that even wild-type susceptible hosts exert defense
      functions that reduce disease severity and pathogen fitness.

PMID- 11310732
TI  - Functional studies of the bacterial avirulence protein AvrPto by mutational
      analysis.
AB  - Pseudomonas syringae pathovars expressing avrPto are avirulent on plants
      expressing the resistance gene Pto. Over 85 mutants of avrPto were generated with
      multiple strategies, and several assays were used to characterize AvrPto
      function. Only a core of 95 amino acids of the 164 residues was sufficient for
      binding Pto in the yeast two-hybrid system. Only nine of 65 mutant proteins of
      AvrPto with amino acid substitutions, created in planta and in vitro, did not
      interact with Pto in the Gal4 yeast two-hybrid system, suggesting that AvrPto can
      tolerate many nonconservative substitutions and still interact with Pto. These
      nine and 12 additional substitution mutants of AvrPto were characterized further.
      The ability to elicit a hypersensitive response and the effect on pathogenesis in
      planta for these 21 mutants of AvrPto were strongly correlated with recognition
      by Pto in the yeast two-hybrid system. Analyses of two proteins with
      substitutions H54P or D52G/L65P indicated that these residues may be required for
      delivery into the host cell and protein stability in the bacterial cytoplasm,
      respectively. The mutants that no longer interacted with Pto and had modified
      activities in planta were predicted to have changes in their secondary structure.

PMID- 11310733
TI  - Most AAL toxin-sensitive Nicotiana species are resistant to the tomato fungal
      pathogen Alternaria alternata f. sp. lycopersici.
AB  - The phytopathogenic fungus Alternaria alternata f. sp. lycopersici produces AAL
      toxins required to colonize susceptible tomato (Lycopersicon esculentum) plants.
      AAL toxins and fumonisins of the unrelated fungus Fusarium moniliforme are
      sphinganine-analog mycotoxins (SAMs), which are toxic for some plant species and
      mammalian cell lines. Insensitivity of tomato to SAMs is determined by the
      Alternaria stem canker gene 1 (Asc-1), and sensitivity is associated with a
      mutated Asc-1. We show that SAM-sensitive species occur at a low frequency in the
      Nicotiana genus and that candidate Asc-1 homologs are still present in those
      species. In Nicotiana spp., SAM-sensitivity and insensitivity also is mediated by
      a single codominant locus, suggesting that SAM-sensitive genotypes are host for
      A. alternata f. sp. lycopersici. Nicotiana umbratica plants homozygous for SAM
      sensitivity are indeed susceptible to A. alternata f. sp. lycopersici. In
      contrast, SAM-sensitive genotypes of Nicotiana spegazzinii, Nicotiana acuminata
      var. acuminata, Nicotiana bonariensis, and Nicotiana langsdorffii are resistant
      to A. alternata f. sp. lycopersici infection concomitant with localized cell
      death. Additional (nonhost) resistance mechanisms to A. alternata f. sp.
      lycopersici that are not based on an insensitivity to SAMs are proposed to be
      present in Nicotiana species.

PMID- 11310734
TI  - Effect of mutations in Pisum sativum L. genes blocking different stages of nodule
      development on the expression of late symbiotic genes in Rhizobium leguminosarum
      bv. viciae.
AB  - In this report, the expression of late symbiotic genes (fnrN, fixN, and nifA) of
      Rhizobium leguminosarum bv. viciae was studied in nodules of mutant pea lines
      blocked at four successive stages of nodule development. Bacterial gene
      expression was analyzed in situ with transcriptional gusA reporter gene fusions.
      As a control, a constitutively expressed gusA gene was included. In the nodules
      of Nop(nodule persistence) mutants (mutant in gene sym13), which had not yet
      exhibited signs of premature senescence, the expression patterns observed were
      identical to those in wild-type nodules. Normal expression of fusions also
      occurred in nodules defective at the infection droplet differentiation stage
      (mutant in gene sym40) in which bacteria are endocytosed, but infection threads
      and infection droplets are hypertrophied. In contrast, in Itn- (infection thread
      formation inside the nodule tissue) mutants (mutant gene sym33), in which there
      is no endocytosis of bacteria, expression of the constitutive fusion was only in
      infection threads and no activity was shown for the other fusions. From this it
      can be concluded that functionality of the plant gene Sym33, i.e., bacterial
      endocytosis, is a prerequisite for the expression of late symbiotic genes in the
      microsymbiont. No morphologically distinct interzone II-III could be detected in
      nodules blocked at the bacteroid differentiation stage (mutants in gene sym31).
      The constitutive fusion was expressed equally throughout the nodule tissue
      (except for the meristem), and the activity of fusions to late symbiotic genes
      increased gradually with a maximal expression level at the base of the nodule.
      This is consistent with an altered oxygen barrier previously reported for these
      nodules. By including double mutants, earlier results on sequential functioning
      of gene pairs sym33-sym40 and sym31-sym13 could be confirmed and it could be
      demonstrated that the developmental epistasis found at the morphological level
      also is reflected in the expression pattern of late symbiotic genes in the
      microsymbiont.

PMID- 11310735
TI  - Induction and signaling of an apoptotic response typified by DNA laddering in the
      defense response of oats to infection and elicitors.
AB  - Cells in the primary leaves of oats displayed internucleosomal DNA cleavage in
      response to incompatible crown rust infection. DNA laddering also was evident in
      leaves treated with calcium ionophore A23187, nonspecific elicitors such as
      chitin and chitosan oligomers, and victorin, which functions as a specific
      elicitor in Pc-2/Vb containing oat leaves. The nuclei in a victorin-treated
      susceptible oat line were positive for the TUNEL assay. These elicitors clearly
      induced a 28-kDa nuclease (p28) in addition to three constitutive nucleases of
      33, 24, and 22 kDa. Activation of p28 preceded the appearance of DNA laddering
      and possibly was mediated by de novo synthesis and/or cysteine protease activity.
      Pharmacological studies showed that the induction of DNA laddering was associated
      with oxidative stress, Ca2+ influx, and serine and cysteine proteases. Protein
      kinase and calmodulin activities did not seem to be involved in the induction of
      DNA laddering by victorin, whereas kinase-mediated signals were involved in DNA
      laddering induced by A23187. Protein kinase, calmodulin, G-protein activities,
      and Ca2+ influx, however, are involved in phytoalexin production. Our results
      imply that p28 is a possible nuclease candidate responsible for the induction of
      DNA laddering. The results also demonstrated that the mediators involved in the
      induction of apoptosis depended on the type of stimuli, whereas p28 and serine
      and cysteine proteases commonly are associated with each elicitor-induced
      apoptosis.

PMID- 11310736
TI  - Reduced expression of the tomato ethylene receptor gene LeETR4 enhances the
      hypersensitive response to Xanthomonas campestris pv. vesicatoria.
AB  - The hypersensitive response (HR) involves rapid death of cells at the site of
      pathogen infection and is thought to limit pathogen growth through the plant.
      Ethylene regulates senescence and developmental programmed cell death, but its
      role in hypersensitive cell death is less clear. Expression of two ethylene
      receptor genes, NR and LeETR4, is induced in tomato (Lycopersicon esculentum cv.
      Mill) leaves during an HR to Xanthomonas campestris pv. vesicatoria, with the
      greatest increase observed in LeETR4. LeETR4 antisense plants previously were
      shown to exhibit increased sensitivity to ethylene. These plants also exhibit
      greatly reduced induction of LeETR4 expression during infection and an
      accelerated HR at inoculum concentrations ranging from 10(5) to 10(7) CFU/ml.
      Increases in ethylene synthesis and pathogenesis-related gene expression are
      greater and more rapid in infected LeETR4 antisense plants, indicating an
      enhanced defense response. Populations of avirulent X. campestris pv. vesicatoria
      decrease more quickly and to a lower level in the transgenic plants, indicating a
      greater resistance to this pathogen. Because the ethylene action inhibitor 1
      methylcyclopropene alleviates the enhanced HR phenotype in LeETR4 antisense
      plants, these changes in pathogen response are a result of increased ethylene
      sensitivity.

PMID- 11310737
TI  - A viral double-stranded RNA up regulates the fungal virulence of Nectria
      radicicola.
AB  - Double-stranded RNAs (dsRNAs) are widespread in plant pathogenic fungi, but their
      functions in fungal hosts remain mostly unclear, with a few exceptions. We
      analyzed dsRNAs from Nectria radicicola, the causal fungus of ginseng root rot.
      Four distinct sizes of dsRNAs, 6.0, 5.0, 2.5, and 1.5 kbp, were detected in 24
      out of the 81 strains tested. Curing tests of individual dsRNAs suggested that
      the presence of 6.0-kbp dsRNA was associated with high levels of virulence,
      sporulation, laccase activity, and pigmentation in this fungus. The 6.0-kbp dsRNA
      cured strains completely lost virulence-related phenotypes. This 6.0-kbp dsRNA
      was reintroduced by hyphal anastomosis to a dsRNA-cured strain marked with
      hygromycin resistance, which resulted in the restoration of virulence-related
      phenotypes. These results strongly suggest that 6.0-kbp dsRNA up regulates fungal
      virulence in N. radicicola. Sequencing of several cDNA clones derived from 6.0
      kbp dsRNA revealed the presence of a RNA-dependent RNA polymerase (RDRP) gene.
      Phylogenetic analysis showed that this gene is closely related to those of plant
      cryptic viruses. Biochemical analyses suggested that the 6.0-kbp dsRNA may
      regulate fungal virulence through signal-transduction pathways involving cyclic
      AMP-dependent protein kinase and protein kinase C.

PMID- 11310738
TI  - Apple contains receptor-like genes homologous to the Cladosporium fulvum
      resistance gene family of tomato with a cluster of genes cosegregating with Vf
      apple scab resistance.
AB  - Scab caused by the fungal pathogen Venturia inaequalis is the most common disease
      of cultivated apple (Malus x domestica Borkh.). Monogenic resistance against scab
      is found in some small-fruited wild Malus species and has been used in apple
      breeding for scab resistance. Vf resistance of Malus floribunda 821 is the most
      widely used scab resistance source. Because breeding a high-quality cultivar in
      perennial fruit trees takes dozens of years, cloning disease resistance genes and
      using them in the transformation of high-quality apple varieties would be
      advantageous. We report the identification of a cluster of receptor-like genes
      with homology to the Cladosporium fulvum (Cf) resistance gene family of tomato on
      bacterial artificial chromosome clones derived from the Vf scab resistance locus.
      Three members of the cluster were sequenced completely. Similar to the Cf gene
      family of tomato, the deduced amino acid sequences coded by these genes contain
      an extracellular leucine-rich repeat domain and a transmembrane domain. The
      transcription of three members of the cluster was determined by reverse
      transcriptionpolymerase chain reaction to be constitutive, and the transcription
      and translation start of one member was verified by 5' rapid amplification of
      cDNA ends. We discuss the parallels between Cf resistance of tomato and Vf
      resistance of apple and the possibility that one of the members of the gene
      cluster is the Vf gene. Cf homologs from other regions of the apple genome also
      were identified and are likely to present other scab resistance genes.

PMID- 11310739
TI  - Effects of the two-component system comprising GacA and GacS of Erwinia
      carotovora subsp. carotovora on the production of global regulatory rsmB RNA,
      extracellular enzymes, and harpinEcc.
AB  - Posttranscriptional regulation mediated by the regulator of secondary metabolites
      (RSM) RsmA-rsmB pair is the most important factor in the expression of genes for
      extracellular enzymes and HarpinEcc in Erwinia carotovora subsp. carotovora. RsmA
      is a small RNA-binding protein, which acts by lowering the half-life of a mRNA
      species. rsmB specifies an untranslated regulatory RNA and neutralizes the RsmA
      effect. It has been speculated that GacA-GacS, members of a two-component system,
      may affect gene expression via RsmA. Because expA, a gacA homolog, and expS (or
      rpfA), a gacS homolog, have been identified in E. carotovora subsp. carotovora,
      we examined the effects of these gacA and gacS homologs on the expression of
      rsmA, rsmB, and an assortment of exoprotein genes. The gacA gene of E. carotovora
      subsp. carotovora strain 71 stimulated transcription of genes for several
      extracellular enzymes (pel-1, a pectate lyase gene; peh-1, a polygalacturonase
      gene; and celV, a cellulase gene), hrpNEcc (an E. carotovora subsp. carotovora
      gene specifying the elicitor of hypersensitive reaction), and rsmB in GacA+ and
      GacS+ E. carotovora subsp. carotovora strains. Similarly, the E. carotovora
      subsp. carotovora gacA gene stimulated csrB (rsmB) transcription in Escherichia
      coli. A GacS- mutant of E. carotovora subsp. carotovora strain AH2 and a GacA-
      mutant of E. carotovora subsp. carotovora strain Ecc71 compared with their parent
      strains produced very low levels of rsmB, pel-1, peh-1, celV, and hrpNEcc
      transcripts but produced similar levels of rsmA RNA and RsmA protein as well as
      transcripts of hyperproduction of extracellular enzymes (Hex) hexA, kdgR
      (repressor of genes for uronate and pectate catabolism), rsmC, and rpoS (gene for
      Sigma-S, an alternate Sigma factor). The levels of rsmB, pel-1, peh-1, celV, and
      hrpNEcc transcripts as well as production of pectate lyase, polygalacturonase,
      cellulase, protease, and HarpinEcc proteins were stimulated in GacS- and GacA-
      mutants by GacS+ or GacA+ plasmids, respectively. The GacA effect on exoenzyme
      genes and hrpNEcc was abrogated in E. carotovora subsp. carotovora mutants
      deficient in RsmA and RsmC or RsmA, RsmC, and rsmB RNA. The expression of lacZ
      transcriptional fusions of rsmB of Erwinia amylovora and Erwinia herbicola pv.
      gypsophilae was markedly reduced in a GacA- and a GacS- mutant of Pseudomonas
      syringae pv. syringae. Southern blot hybridization revealed the presence of gacA
      and gacS homologs in all tested strains of soft-rotting Erwinia spp. and several
      nonsoft-rotting Erwinia species such as E. amylovora, E. rhapontici, E.
      herbicola, E. stewartii, and E. herbicola pv. gypsophilae. These findings
      establish that the GacA-GacS system controls transcription of rsmB of E.
      carotovora subsp. carotovora, E. amylovora, and E. herbicola pv. gypsophilae and
      support the hypothesis that the effects of this two-component system on
      extracellular protein production in E. carotovora subsp. carotovora is mediated,
      at least in part, via the levels of rsmB transcripts.

PMID- 11310740
TI  - A novel jasmonic acid-inducible rice myb gene associates with fungal infection
      and host cell death.
AB  - Endogenous signal molecules such as jasmonic acid (JA) and salicylic acid (SA)
      play an important role in induced resistance against pathogen infection and
      insect herbivory. In rice seedlings, JA is an effective inducer of systemic
      acquired resistance (SAR) against infection of blast fungus (Pyricularia grisea).
      To gain further insights into JA-mediated defense signaling pathways, we isolated
      and characterized a pathogen- and JA-induced rice gene (JAmyb) that encodes a Myb
      transcription factor. The JAmyb gene was induced within 1 day after fungal
      infection in resistant and susceptible interactions prior to lesion formation.
      Unlike most defense-related genes that are activated faster and stronger in
      resistant interactions, JAmyb induction by blast fungus is much higher in
      susceptible interactions, accompanied by large lesions and extensive tissue
      damage. Significant induction of JAmyb also was observed during cell death and
      lesion formation in certain lesion mimic mutants. Interestingly, JAmyb was
      activated rapidly by JA or wounding, independent of de novo protein synthesis,
      but not by other endogenous signal molecules such as SA and abscisic acid or SAR
      inducers such as benzothiadiazole and probenazole. We used SA-deficient
      transgenic plants to further demonstrate that depletion of SA in rice did not
      abolish but rather enhanced blast-induced JAmyb expression. These results suggest
      that JAmyb is related closely to host cell death and is involved in the JA
      mediated, SA-independent signaling pathways in rice.

PMID- 11310741
TI  - Signal peptide-selection of cDNA cloned directly from the esophageal gland cells
      of the soybean cyst nematode Heterodera glycines.
AB  - Secretions from the esophageal gland cells of plant-parasitic nematodes play
      critical roles in the nematode-parasitic cycle. A novel method to isolate cDNA
      encoding putative nematode secretory proteins was developed that utilizes mRNA
      for reverse transcription-polymerase chain reaction derived from microaspiration
      of the esophageal gland cell contents of parasitic stages of the soybean cyst
      nematode Heterodera glycines. The resulting H. glycines gland cell cDNA was
      cloned into the pRK18 vector, and plasmid DNA was transformed into a mutated
      yeast host for specific selection of cDNA inserts that encode proteins with
      functional signal peptides. Of the 223 cDNA clones recovered from selection in
      yeast, 97% of the clones encoded a predicted signal peptide. Fourteen unique cDNA
      clones hybridized to genomic DNA of H. glycines on Southern blots and, among
      them, nine cDNA clones encoded putative extracellular proteins, as predicted by
      PSORT II computer analysis. Four cDNA clones hybridized to transcripts within the
      dorsal esophageal gland cell of parasitic stages of H. glycines, and in situ
      hybridization within H. glycines was not detected for eight cDNA clones. The
      protocol provides a direct means to isolate potential plant-parasitic nematode
      esophageal gland secretory protein genes.

PMID- 11310742
TI  - Isolation and characterization of the gene coding for the amidinotransferase
      involved in the biosynthesis of phaseolotoxin in Pseudomonas syringae pv.
      phaseolicola.
AB  - Pseudomonas syringae pv. phaseolicola is the causal agent of the "halo blight"
      disease of beans. A key component in the development of the disease is a nonhost
      specific toxin, Ndelta-(N'-sulphodiaminophosphinyl)-ornithyl-alanyl-homoarginine,
      known as phaseolotoxin. The homoarginine residue in this molecule has been
      suggested to be the product of L-arginine:lysine amidinotransferase activity,
      previously detected in extracts of P. syringae pv. phaseolicola grown under
      conditions of phaseolotoxin production. We report the isolation and
      characterization of an amidinotransferase gene (amtA) from P. syringae pv.
      phaseolicola coding for a polypeptide of 362 residues (41.36 kDa) and showing
      approximately 40% sequence similarity to L-arginine:inosamine-phosphate
      amidinotransferase from three species of Streptomyces spp. and 50.4% with an L
      arginine:glycine amidinotransferase from human mitochondria. The cysteine,
      histidine, and aspartic acid residues involved in substrate binding are
      conserved. Furthermore, expression of the amtA and argK genes and phaseolotoxin
      production occurs at 18 degrees C but not at 28 degrees C. An amidinotransferase
      insertion mutant was obtained that lost the capacity to synthesize homoarginine
      and phaseolotoxin. These results show that the amtA gene isolated is responsible
      for the amidinotransferase activity detected previously and that phaseolotoxin
      production depends upon the activity of this gene.

PMID- 11310743
TI  - Purification of the major outer membrane protein of Azospirillum brasilense, its
      affinity to plant roots, and its involvement in cell aggregation.
AB  - The major outer membrane protein (MOMP) of the nitrogen-fixing rhizobacterium
      Azospirillum brasilense strain Cd was purified and isolated by gel filtration,
      and antiserum against this protein was obtained. A screening of the binding of
      outer membrane proteins (OMPs) of A. brasilense to membrane-immobilized root
      extracts of various plant species revealed different affinities for the MOMP,
      with a stronger adhesion to extracts of cereals in comparison with legumes and
      tomatoes. Moreover, this protein was shown to bind to roots of different cereal
      seedlings in an in vitro adhesion assay. Incubation of A. brasilense cells with
      MOMP-antiserum led to fast agglutination, indicating that the MOMP is a surface
      exposed protein. Cells incubated with Fab fragments obtained from purified MOMP
      antiserum immunoglobulin G exhibited significant inhibition of bacterial
      aggregation as compared with controls. Bacteria preincubated with Fab fragments
      showed weaker adhesion to corn roots in comparison to controls without Fab
      fragments. These findings suggest that the A. brasilense MOMP acts as an adhesin
      involved in root adsorption and cell aggregation of this bacterium.

PMID- 11310744
TI  - The ABC transporter BcatrB affects the sensitivity of Botrytis cinerea to the
      phytoalexin resveratrol and the fungicide fenpiclonil.
AB  - During pathogenesis, fungal pathogens are exposed to a variety of fungitoxic
      compounds. This may be particularly relevant to Botrytis cinerea, a plant
      pathogen that has a broad host range and, consequently, is subjected to exposure
      to many plant defense compounds. In practice, the pathogen is controlled with
      fungicides belonging to different chemical groups. ATP-binding cassette (ABC)
      transporters might provide protection against plant defense compounds and
      fungicides by ATP-driven efflux mechanisms. To test this hypothesis, we cloned
      BcatrB, an ABC transporter-encoding gene from B. cinerea. This gene encodes a
      1,439 amino acid protein with nucleotide binding fold (NBF) and transmembrane
      (TM) domains in a [NBF-TM6]2 topology. The amino acid sequence has 31 to 67%
      identity with ABC transporters from various fungi. The expression of BcatrB is up
      regulated by treatment of B. cinerea germlings with the grapevine phytoalexin
      resveratrol and the fungicide fenpiclonil. BcatrB replacement mutants are not
      affected in saprophytic growth on different media but are more sensitive to
      resveratrol and fenpiclonil than the parental isolate. Furthermore, virulence of
      deltaBcatrB mutants on grapevine leaves was slightly reduced. These results
      indicate that BcatrB is a determinant in sensitivity of B. cinerea to plant
      defense compounds and fungicides.

PMID- 11310745
TI  - A purine-related metabolite negatively regulates fixNOQP expression in
      Sinorhizobium meliloti by modulation of fixK expression.
AB  - 5-aminoimidazole-4-carboxamide nucleotide (AICAR) is a negative effector of
      cytochrome terminal oxidase cbb3 production in Rhizobium etli. In this work, the
      effect of AICAriboside (AICAr), the precursor of AICAR on the expression of the
      Sinorhizobium meliloti fixNOQP operon encoding the symbiotic terminal oxidase
      cbb3, was analyzed. AICAr reduced the microaerobic induction levels of fixN-lacZ
      and fixT-lacZ gene fusions 18- and seven-fold respectively, and both genes were
      activated by the transcriptional activator FixK. A fixK-lacZ fusion presented 14
      fold-reduced induction levels in microaerobic cell cultures in the presence of
      AICAr. AICAr also reduced three-fold the microaerobic expression levels of the
      nifA-lacZ fusion, whose expression as well as that of fixK is controlled by the
      two-component system FixL-FixJ. In contrast, AICAr had no effect on the
      expression levels of a hemA-lacZ fusion. These data suggest that AICAr prevents
      fixNOQP induction by the inhibition of fixK transcription.

PMID- 11310746
TI  - Novel constructions to enable the integration of genes into the Agrobacterium
      tumefaciens C58 chromosome.
AB  - We constructed several versatile sets of vectors that can be used to introduce
      any gene into the pgl/picA locus of the Agrobacterium tumefaciens C58 chromosome
      without affecting T-DNA transfer. One set contains a fragment containing the
      lacIq and lacZ genes and a multiple cloning site from pBluescriptII SK(+)
      inserted into a PstI site between the pgl and picA genes on an incPalpha plasmid.
      The resulting plasmid contains eight unique restriction endonuclease sites and
      the ability to use blue-white screening for the presence of an insert. A second
      plasmid also contains a beta-lactamase gene within this locus and provides a
      convenient ampicillin-carbenicillin resistance marker for the selection of genes
      integrated into the chromosome following double homologous recombination
      (homogenotization). A third plasmid contains, in addition to the lacZ, lacIq, and
      beta-lactamase genes within the pgl/picA locus, a sacRB gene cassette within the
      vector to counterselect against the presence of the vector within A. tumefaciens.
      To test this system, we introduced a wild-type virD2 gene into the A. tumefaciens
      chromosome at the pgl/picA locus. When a Ti plasmid harboring a deletion of virD2
      was in this strain, the integrated virD2 gene complemented the virD2 deletion and
      the resulting transformation phenotype was identical to that resulting from A.
      tumefaciens strains harboring a wild-type virD2 gene located on a replicating
      plasmid.

PMID- 11310747
TI  - Mutation of an arginine biosynthesis gene causes reduced pathogenicity in
      Fusarium oxysporum f. sp. melonis.
AB  - Restriction enzyme-mediated integration (REMI) mutagenesis was used to tag genes
      required for pathogenicity of Fusarium oxysporum f. sp. melonis. Of the 1,129
      REMI transformants tested, 13 showed reduced pathogenicity on susceptible melon
      cultivars. One of the mutants, FMMP95-1, was an arginine auxotroph. Structural
      analysis of the tagged site in FMMP95-1 identified a gene, designated ARG1, which
      possibly encodes argininosuccinate lyase, catalyzing the last step for arginine
      biosynthesis. Complementation of FMMP95-1 with the ARG1 gene caused a recovery in
      pathogenicity, indicating that arginine auxotrophic mutation causes reduced
      pathogenicity in this pathogen.

PMID- 11310748
TI  - Morphometric study of regeneration through vascularized nerve graft in a rabbit
      sciatic nerve model.
AB  - Adequate vascularization is essential for a successful nerve graft.
      Theoretically, immediate vascularization will minimize fibroblast infiltration
      and support axonal regeneration. In this study, histomorphologic and morphometric
      studies were carried out to determine whether vascularized grafts are beneficial,
      in terms of axonal regeneration. In a rabbit model, 4-cm segments of sciatic
      nerve were obtained and placed as a nonvascularized graft on one side, and as a
      pedicled vascularized graft fed by the inferior gluteal vessel on the
      contralateral side. Histomorphologically, the distribution of myelinated nerve
      fibers and Schwann cells was evaluated after toluidine blue staining, at 2-, 3-,
      and 4-month intervals. The following results were obtained. 1) Myelinated nerve
      fibers were more abundant in the proximal, middle, and distal segments of the
      vascularized nerve group at 2 and 3 months. 2) The average nerve-fiber diameter
      was greater in the vascularized nerve graft group at 2, 3, and 4 months (2 to 10
      microm). 3) Schwann cells were more abundant in the proximal, middle, and distal
      segments of the vascularized nerve graft group at all time points. Based on the
      above findings, the immediate restoration of circulation in the vascularized
      nerve graft can be accountable for the increased number of surviving Schwann
      cells, the rapid clearing of axons, and myelin-sheath changes that occur during
      Wallerian degeneration, thus enabling "morphologically" optimal regeneration.

PMID- 11310749
TI  - A study of induction of nerve regeneration using bioabsorbable tubes.
AB  - A silicone tube (S-tube) was packed with CPLA (copolymer of poly-L-lactide)
      fibers (S-tube+CPLA) or collagen fibers (S-tube+fiber). Two types of tube were
      prepared from a collagen sheet (Col-tube) and a bioabsorbable atelocollagen
      membrane for guided tissue regeneration (GTR-tube). They were packed with
      collagen fibers or films (Col-tube+fiber, GTR-tube+fiber and GTR-tube+film).
      Bridge grafting (15 mm in length) was performed with these tubes in a rat sciatic
      nerve model. Specimens were harvested after 8 weeks. Minifascicles were formed in
      the open space between the CPLA fibers in the S-tube+CPLA group. Regenerated
      axons were also formed in the degenerated collagen fibers in the S-tube+Col
      group. Immunocytochemistry evaluation revealed that Schwann cells invaded the
      space in the absorbing collagen fibers. Histologic analysis of the regenerated
      axons in the groups with Col-tubes or GTR-tubes revealed that both the Col-tube
      and the GTR-tube packed with collagen fibers were effective in providing a
      scaffold for regenerating nerve tissue.

PMID- 11310750
TI  - Vascularized orthotopic osteochondral transplantation of the canine proximal
      femur.
AB  - Osteochondral vascularized proximal femoral allografts were orthotopically
      transplanted in five adult beagles (four experimental and one control). The
      experimental animals were placed on 0.1 mg/kg of FK506 intravenously for 7 days,
      and then converted to 1.0 mg/kg orally. Biopsies of the femoral heads were taken
      at 3 weeks postoperatively and at 1-month intervals thereafter. The specimens
      were studied histologically with a hemotoxylin and eosin staining technique. Bone
      biopsies showed no microscopic evidence of rejection, and only minimal evidence
      of necrosis. Patency of the microvascular anastomosis was confirmed with bone
      scanning, using technitium 99m phosphate, arteriograms, and by Doppler flowmeter.
      All animals had an uneventful postoperative course, with achievement of full
      weight-bearing status by postoperative day 10, and normal activity by 1 month
      postoperatively. There were no infections or hip dislocations. One animal
      sustained a femoral neck fracture and was sacrificed at 4 months. At 6 months,
      the remaining animals were sacrificed. At necropsy, the experimental animals and
      the normal dog showed viable chondrocytes and osteocytes, with minimal bone
      necrosis. No dislocations or allograft rejections were observed. Based on this
      small series, a successful technique has been developed for orthotopic
      transplantation of a vascularized hip joint in a canine model.

PMID- 11310751
TI  - Double-blind randomized study evaluating regeneration of the rat transected
      sciatic nerve after suturing and postoperative low-power laser treatment.
AB  - This double-blind randomized study evaluated the therapeutic effect of low-power
      laser irradiation (LPLI) on peripheral nerve regeneration, after complete
      transection and direct anastomosis of the rat sciatic nerve. After this
      procedure, 13 of 24 rats received postoperative LPLI, with a wavelength of 780 nm
      laser, applied transcutaneously, 30 min daily for 21 consecutive days, to
      corresponding segments of the spinal cord and to the injured sciatic nerve.
      Positive somatosensory evoked responses were found in 69.2 percent of the
      irradiated rats (p = 0.019), compared to 18.2 percent of the non-irradiated rats.
      Immunohistochemical staining in the laser-treated group showed an increased total
      number of axons (p = 0.026), and better quality of the regeneration process, due
      to an increased number of large-diameter axons (p = 0.021), compared to the non
      irradiated control group. The study suggests that postoperative LPLI enhances the
      regenerative processes of peripheral nerves after complete transection and
      anastomosis.

PMID- 11310752
TI  - Thromboxane A2 release in ischemia and reperfusion of free flaps in rats, studied
      by microdialysis.
AB  - Several studies have implicated enhanced eicosanoid production in reperfusion
      injury. The reported study investigated the use of microdialysis in the in vivo
      measurement of thromboxane levels during reperfusion in ischemic and reperfused
      experimental free muscle flaps. Microdialysis probes were inserted, via a guide,
      into the gracilis and semitendinosus free flap in the rat. The probe was perfused
      at a flow of 5 microl/min, with samples collected at intervals of 20 min, and
      analyzed by the ELISA technique. Animals were randomly distributed into three
      groups. After ischemic periods of 2, 4, and 6 hr, respectively, the free muscle
      flaps were revascularized on the contralateral femoral vessels. The mean
      thromboxane level during ischemia was 1785.34 +/- 124.81 pg/ml. The mean levels
      of thromboxane rose significantly (p < 0.05), compared to base level, with 151.65
      percent in the 2-hr ischemia group, 192.33 percent in the 4-hr ischemia group,
      and 294.69 percent in the 6-hr ischemia group, and correlated well with
      histologic observations. The results suggest that a microdialysis technique,
      combined with a sensitive assay for measuring thromboxane, is a useful method for
      in vivo monitoring of inflammatory processes during ischemia and reperfusion. The
      evolution of thromboxane release following 6 hr of ischemia indicates that this
      mediator may be involved in facilitation of cell death, following ischemia and
      reperfusion, since its tissue level correlates with histologic tissue damage.

PMID- 11310753
TI  - Correction of scapular winging by supraclavicular neurolysis of the long thoracic
      nerve.
AB  - Injury to the long thoracic nerve results in winging of the scapula. When there
      is no known direct site of injury to this nerve, the traditional treatment
      consists of bracing the shoulder and, if recovery of function does not occur,
      then carrying out a muscle transfer to reconstitute the forces required to bring
      the scapula into appropriate position with respect to the thorax. The present
      report describes four patients in whom a site of compression of the long thoracic
      nerve within the scalene muscles proved to be the site of compression. A
      supraclavicular neurolysis of the long thoracic nerve resulted in correction of
      the winged scapula in all four of these patients.

PMID- 11310754
TI  - Digital neurorrhaphy after the age of 60 years.
AB  - Fifteen patients over the age of 60 years (average age: 65 years), with 19
      digital nerve lacerations, were evaluated more than 1 year after injury. Two
      point discrimination, Semmes-Weinstein evaluation, and subjective return of
      sensibility were examined by a certified hand therapist before and after local
      anesthetic block of the uninjured digital nerve. Sixty-three percent of the
      patients regained moving two-point discrimination less than 15 mm; 100 percent
      regained Semmes-Weinstein values of less than 4.56; and 84 percent of the
      patients subjectively noted greater than half of their normal sensation.
      Crossover innervation was a factor in four of 14 repairs. Based on the data,
      useful sensation can be regained by repairing a digital nerve in the majority of
      patients older than 60 years of age.

PMID- 11310755
TI  - Role of medical students in microsurgery research.
AB  - Microsurgery is an integral element in many surgical specialties, as well as an
      important technique for surgical research. Student participation in microsurgery
      research programs can be a source for both high quality training in skills and
      for research contributions. In this article, the authors review their experience
      in developing general principles for setting up medical student microsurgery
      research programs, and analyze the research output and career choices made by the
      students who have participated.

PMID- 11310756
TI  - Latissimus dorsi musculocutaneous flap based on the serratus branch with
      microvascular venous augmentation.
AB  - The authors report a case of a latissimus dorsi musculocutaneous flap with
      microvascular venous supercharging in the setting of an acute ligation of the
      thoracodorsal vascular pedicle. Through their experience with this case, they
      have questioned a common belief that the flap will survive without the
      thoracodorsal vessels intact. They accept that risk is minimized when rotation of
      the flap takes place several weeks after ligation of the vessels. However, they
      do not believe it is prudent to transfer a latissimus flap of significant size
      immediately after ligation of the thoracodorsal vessels, unless the vascular
      supply is enhanced.

PMID- 11310757
TI  - Terminolateral neurorrhaphy: review of experimental and clinical studies.
AB  - Since the reintroduction of the terminolateral neurorrhaphy (TLN) concept by
      Viterbo in 1992, several published articles and abstracts have been reported in
      the English literature. This report was prepared to investigate the following
      subjects: source of current research on TLN, animal models, methods of assessment
      of axonal regeneration, the source of regenerating axons, sensory vs. motor
      collateral sprouting, effects on the donor nerve, cellular events following TLN,
      factors affecting axonal regeneration and, finally, end-to-side nerve repair in
      the human patient.

PMID- 11310758
TI  - Preliminary in vitro study of the histological effects of low fluence 193-nm
      excimer laser irradiation of corneal tissue.
AB  - PURPOSE: To determine if moderate numbers of low fluence, 193-nm excimer laser
      pulses modify or damage the corneal stroma. METHODS: The corneal epithelium of
      fresh bovine eyes was scraped off and the exposed stroma was irradiated with 200
      low fluence laser pulses from an argon fluoride excimer laser. This process was
      performed on five eyes each at two laser fluences, 10 mJ/cm2 and 30 mJ/cm2. The
      ten irradiated and three control (unirradiated) corneas were sectioned and
      studied by electron microscopy. The maximum and minimum thickness of the anterior
      layer of randomly oriented collagen fibers was measured using electron
      microscopy. RESULTS: The mean maximum thickness of the anterior randomly oriented
      layer of collagen was 1.23 +/- 0.45 microm in the control corneas, 0.67 +/- 0.32
      microm in the corneas irradiated at 10 mJ/cm2, and 0.10 +/- 0.12 microm in the
      corneas irradiated at 30 mJ/cm2. The mean thickness of corneal stroma removed was
      0.7 microm at a fluence of 10 mJ/cm2 and 1.1 microm at a fluence of 30 mJ/cm2. A
      thin, electron-dense pseudomembrane was present at both fluences. CONCLUSION: We
      report removal of bovine corneal stroma at 10 mJ/cm2--below the previously
      reported ablation threshold of 20 mJ/cm2.

PMID- 11310759
TI  - Central necrotic lamellar inflammation after laser in situ keratomileusis.
AB  - PURPOSE: To report four cases of corneal interface complications that occurred
      after excimer laser in situ keratomileusis (LASIK). METHODS: Four eyes of three
      patients underwent technically uneventful LASIK. RESULTS: One day after LASIK,
      patients presented with severe pain, blurred vision, conjunctival infection, and
      diffuse opacity at the interface. Two days after LASIK, significant features were
      central opacity, striae in the flap, loss of uncorrected and best spectacle
      corrected visual acuity, and corneal sensitivity. The findings did not improve by
      using drugs or by lifting the flap and irrigating the bed. The central opacity
      partially resolved over 8 to 12 months, leaving a hyperopic shift (one patient),
      striae (one patient), and loss of two or more lines of best spectacle-corrected
      visual acuity (three patients). CONCLUSION: This severe central inflammation
      after LASIK could be an extreme manifestation of diffuse lamellar keratitis.

PMID- 11310760
TI  - Laser in situ keratomileusis for the correction of hyperopia from +1.25 to +5.00
      diopters with the Technolas Keracor 117C laser.
AB  - PURPOSE: To assess the efficacy, predictability, stability, and safety of laser
      in situ keratomileusis (LASIK) in patients with hyperopia and to evaluate the
      visual and refractive results of the procedure. METHODS: LASIK was performed on
      85 eyes of 53 patients for correction of hyperopia, with a preoperative mean
      manifest spherical equivalent refraction of +3.31 +/- 0.69 D (range, +1.25 to
      +5.00 D) and mean refractive astigmatism of +0.91 +/- 1.06 D (range, 0 to +3.00
      D). The Carriazo-Barraquer (Moria) manual microkeratome was used to create the
      corneal flap, and laser ablation was performed using the Technolas Keracor 117C
      excimer laser with an ablation zone diameter of 6.0 mm and a transition zone
      diameter to 9.0 mm. Follow-up was 12 months for all patients. RESULTS: Refraction
      was stable by 3 months after surgery. At 1 year after LASIK, the mean manifest
      spherical equivalent refraction was +0.43 +/- 0.57 D (range, -1.25 to +2.00 D)
      and refractive astigmatism was reduced to a mean of 0.36 +/- 0.30 D (range, 0 to
      1.00 D). Fifty-two eyes (61.2%) had a manifest spherical equivalent refraction
      within +/- 0.50 D of emmetropia, and 76 eyes (89.4%) were within +/- 1.00 D.
      Uncorrected visual acuity was 20/20 in 21 eyes (24.7%) and 20/40 or better in 79
      eyes (92.9%). Spectacle-corrected visual acuity was reduced by two lines in one
      eye (1.2%) and improved by two lines in five eyes (5.9%). There were no
      significant complications. CONCLUSION: LASIK was an effective, safe, and
      predictable procedure for the correction of hyperopia up to +5.00 D and hyperopic
      astigmatism up to +3.00 D with the Technolas Keracor 117C excimer laser. The
      large size of the corneal flap obtained by the Carriazo-Barraquer (Moria) manual
      microkeratome facilitated laser ablation entirely in the exposed corneal stromal
      bed.

PMID- 11310761
TI  - Laser in situ keratomileusis for the correction of hyperopia from +0.50 to +11.50
      diopters with the Keracor 117C laser.
AB  - PURPOSE: To evaluate excimer laser in situ keratomileusis (LASIK) for the
      correction of hyperopia. METHODS: We reviewed retrospectively the medical records
      of 46 patients treated with LASIK for hyperopia. All patients had a complete
      ophthalmologic evaluation. The corneal bed was ablated using the Bausch & Lomb
      Chiron Keracor 117C excimer laser to create a paracentral annular ablation under
      a nasally hinged 160-microm corneal flap with the Chiron Automatic Corneal Shaper
      microkeratome. Follow-up was a minimum of 6 months. RESULTS: Eighty eyes of 46
      patients (23 males and 23 females) were included. Age ranged from 18 to 65 years
      (mean, 42 yr). The range of preoperative spherical equivalent refraction was
      +0.50 to +11.50 D (mean, +3.40 D). Mean postoperative spherical equivalent
      refraction at 6 months was +0.26 D. Six months after surgery, 35 eyes (44%)
      achieved uncorrected visual acuity of 20/20 or better and 78 eyes (97.5%)
      achieved 20/40 or better. Forty-six eyes (58%) had a postoperative spherical
      equivalent refraction within +/-0.50 D of attempted correction, and 67 eyes (84%)
      were within +/-1.00 D of attempted correction. When using the Bausch & Lomb
      Chiron Keracor 117C excimer laser to correct hyperopia, eyes with a spherical
      equivalent refraction less +2.00 D should be overcorrected by 25%, +2.00 to +4.00
      D by 30%, and over +4.00 by 40%. The positive cylinder should be overcorrected by
      10%. CONCLUSIONS: LASIK was safe and effective in the treatment of hyperopia from
      +0.50 to +11.50 D. Regression following LASIK for hyperopia remains a problem. A
      special nomogram was required to achieve results comparable with those for
      myopia.

PMID- 11310762
TI  - Correlation between refractive and corneal topographic changes after
      photorefractive keratectomy for myopia.
AB  - PURPOSE: To compare videokeratographic and refractive data obtained before and
      after photorefractive keratectomy (PRK) for myopia. METHODS: Seventy-four eyes
      underwent PRK for myopia ranging from -2.50 to -17.00 D (mean, -7.76 +/- 3.17 D).
      All patients had videokeratography with the EyeSys instrument before, and 1 and 6
      months after PRK, and the changes in three corneal power measurements (center of
      the ablation, apex, and effective refractive power) were compared with refractive
      changes. RESULTS: Changes obtained in the three corneal power measurements at 1
      and 6 months were well correlated with manifest refraction (Pearson's coefficient
      ranged from 0.71 to 0.84). CONCLUSION: Power measurements obtained with corneal
      topography, as described above, are a reliable and objective method for the
      evaluation and follow-up of PRK, provided addition of an approximate 25%
      correcting factor.

PMID- 11310763
TI  - The sense of self-concept change in patients after radial keratotomy.
AB  - PURPOSE: The study focuses on the problem of self-concept change in patients
      after radial keratotomy. METHODS: Twenty-five patients (17 female, 8 male) were
      studied from 6 to 18 months after radial keratotomy using the Adjective Check
      List by Gough and Heilbrun with the application of double instruction. It
      concerned self-concept change over a period of observation after surgery, as
      compared to retrospective (preoperative) self-concept. RESULTS: For current self
      concept, patients obtained significantly higher results in the following
      measures: the number of positive words used for self-description (P < .05); need
      scales, like affiliation (P < .005), heterosexuality (P < .01), and intraception
      or insight (P < .05); self-confidence (P < .01); military leadership (P < .05),
      logical decision making (P < .05); two measures concerning logical-analytical
      thinking (P < .05). CONCLUSIONS: The results indicate that after radial
      keratotomy, patients perceived themselves in a more positive way than before
      surgery, especially as more self-confident in interpersonal functioning.

PMID- 11310764
TI  - Penetrating keratoplasty vs. epikeratoplasty for the surgical treatment of
      keratoconus.
AB  - PURPOSE: Penetrating keratoplasty and epikeratoplasty have been utilized in the
      surgical treatment of keratoconus. Comparison of the relative efficacy of each
      procedure in achieving visual outcomes has not been achieved due to limited
      numbers of cases and follow-up in previous series. METHODS: All patients who
      underwent either penetrating keratoplasty or epikeratoplasty for keratoconus
      between January 1987 and December 1997, and for whom at least 24 months of
      postoperative follow-up data for visual acuity was documented in the medical
      record, were included in this retrospective, nonrandomized, sequential
      comparative trial. The sole criteria for outcome in each group, as well as for
      comparison of the two groups, was Snellen visual acuity measured at the time of
      each follow-up with the presenting optical aid. RESULTS: Inclusion criteria were
      met for 443 eyes treated with penetrating keratoplasty and 161 eyes treated with
      epikeratoplasty. Mean follow-up was 4.3 years for penetrating keratoplasty and
      4.5 years for epikeratoplasty. In each group, approximately 50% of the patients
      chose rehabilitation with optical correction with either spectacles or contact
      lenses and 50% chose no optical correction. Final median logMAR visual acuity for
      all patients, irrespective of means of visual rehabilitation, was 0.30 (20/40)
      for penetrating keratoplasty and 0.40 (20/50) for epikeratoplasty (P < .00005).
      In 209 penetrating keratoplasty and 77 epikeratoplasty eyes with optical
      correction, the final median logMAR visual acuity was 0.18 (20/30) for
      penetrating keratoplasty and 0.40 (20/50) for epikeratoplasty (P < .00005). The
      final median logMAR visual acuity in 234 penetrating keratoplasty and 84
      epikeratoplasty eyes without optical correction was 0.48 (20/60) in both groups
      (P-value was not statistically significant). CONCLUSIONS: Although penetrating
      keratoplasty was statistically superior to epikeratoplasty with respect to visual
      outcome, results with epikeratoplasty were adequate to recommend its use as a
      surgical alternative in cases when it is not desirable to perform penetrating
      keratoplasty.

PMID- 11310765
TI  - Polymicrobial keratitis after laser in situ keratomileusis.
AB  - PURPOSE: To report a case of polymicrobial infectious keratitis in one eye of a
      patient who had undergone bilateral simultaneous laser in situ keratomileusis
      (LASIK). METHODS: A 21-year-old healthy female developed infectious keratitis in
      her right eye after bilateral LASIK surgery. Material obtained from the infective
      foci was sent for bacterial and fungal cultures and herpes simplex virus antigen
      detection, and broad spectrum antimicrobial therapy was instituted. RESULTS:
      Staphylococcus epidermidis and Fusarium solani were detected on culture and
      herpes simplex virus antigen was found to be positive. The patient did not
      respond to medical therapy and subsequently the ulcer perforated. A therapeutic
      keratoplasty was performed and the final best-corrected visual acuity was 20/40,
      1 month after keratoplasty. CONCLUSION: Polymicrobial infectious keratitis,
      although rare, is a potential sight-threatening complication of LASIK.

PMID- 11310766
TI  - Surgically-induced astigmatism after LASIK for spherical myopia.

PMID- 11310767
TI  - Surgically-induced astigmatism after LASIK for spherical myopia.

PMID- 11310769
TI  - Early rhegmatogenous retinal detachment following LASIK.

PMID- 11310768
TI  - Refractive surgery advertising.

PMID- 11310771
TI  - Posterior chamber phakic intraocular lens.

PMID- 11310770
TI  - Microkeratome cut edges and surface characteristics.

PMID- 11310772
TI  - Change in intraocular pressure in myopic eyes measured with contact and non
      contact tonometers after laser in situ keratomileusis.
AB  - PURPOSE: To study the change in the intraocular pressure (IOP) after laser in
      situ keratomileusis (LASIK) for correction of myopia. METHODS: One hundred twenty
      consecutive myopic eyes (60 patients) were included in a prospective study. All
      eyes received LASIK with the Nidek EC-5000 excimer laser and the Chiron Automated
      Corneal Shaper. Baseline refraction, keratometry, pachymetry, ablation depth, and
      IOP measured by Goldmann applanation tonometry and non-contact air puff tonometry
      were correlated with the IOP change after surgery. Sixty healthy eyes of 30
      subjects served as controls. RESULTS: At 6 months, 108 eyes (90%) were examined.
      Compared to preoperative values, IOP decreased in 103 eyes (95.4%) when measured
      with applanation tonometry; it decreased in all eyes when measured with air puff
      tonometry. Mean change in IOP was -4.3 +/- 2.1 mmHg (range, -10.0 to +1.0 mmHg)
      with the applanation and -6.1 +/- 2.3 mmHg (range, -12.0 to -1.0 mmHg) with air
      puff tonometry. The IOP change measured with either instrument correlated
      significantly with the baseline IOP (P < .001) and the ablation depth (air puff,
      P < .001, applanation; P = .006). CONCLUSION: Intraocular pressure decreased
      significantly after LASIK when measured with either Goldmann (mean 4.3 mmHg) or
      air puff (mean 6.1 mmHg) tonometers. This decrease may delay the diagnosis or
      affect the management of future glaucoma that may develop in a myopic eye that
      received LASIK.

PMID- 11310773
TI  - The new childhood growth charts.
AB  - New childhood growth percentiles have been published recently by the Centers for
      Disease Control and Prevention, and are designed to replace the widely used 1977
      National Center for Heath Statistics percentiles. International definitions for
      overweight and obesity in childhood, based on the body mass index, also have been
      published. This review discusses appropriate uses of the new percentile charts
      and international definitions of overweight.

PMID- 11310774
TI  - Meat consumption and colorectal cancer: a review of epidemiologic evidence.
AB  - This article reviews the epidemiologic evidence on colorectal cancer risk and
      meat consumption from 32 case-control and 13 cohort studies published in English
      from 1970 to 1999 and retrieved from the Medline database. The results support
      the hypothesis that meat consumption is associated with a modest increase in
      colorectal cancer risk. This association, however, seems to have been more
      consistently found for red meat and processed meat. The studies on cooking
      methods and meat "doneness" are not consistent and the evidence is not
      conclusive.

PMID- 11310775
TI  - Resistance to weight gain during overfeeding: a NEAT explanation.
AB  - Individuals vary in susceptibility to weight gain in response to overeating;
      however, the reason for such variation has never been clear. A recent study of 16
      nonobese young adults followed on an ambulatory basis for 8 weeks found that
      changes in nonexercise activity thermogenesis (NEAT) account for the variations
      in fat storage that occur in response to experimentally controlled overeating.
      NEAT is the thermogenesis that accompanies physical activity other than
      volitional exercise. Individuals in whom overeating effectively activates NEAT
      dissipate as much as 69% of the excess energy as heat. Those less able to
      activate NEAT store a higher proportion of the excess calories as fat. Other
      studies have shown that genotype is an important determinant of resistance to
      overfeeding-induced weight gain. Spontaneous weight gain is accompanied by rises
      in plasma norepinephrine, insulin, and leptin levels, suggesting that a change in
      autonomic nervous system activity or in pattern of hormonal secretion might play
      a role in the activation of overeating-induced NEAT

PMID- 11310776
TI  - A diet containing food rich in soluble and insoluble fiber improves glycemic
      control and reduces hyperlipidemia among patients with type 2 diabetes mellitus.
AB  - The clinical significance of fiber on metabolic control among people with type 2
      diabetes is debatable. Patients with type 2 diabetes who consumed a diet
      containing food naturally rich in fiber (e.g., 50 g fiber/day, 50% soluble) for 6
      weeks had significant improvements in glycemic control and lipid panels when
      compared with patients who consumed a diet with moderate amounts of fiber (e.g.,
      25 g fiber/day, 50% soluble). Whether this high intake of fiber-rich food,
      especially fruits, can be maintained, tolerated without side effects or
      micronutrient deficiencies, and affordable for longer than 6 weeks in people with
      type 2 diabetes remains to be determined.

PMID- 11310777
TI  - The uncoupling proteins UCP2 and UCP3 in skeletal muscle.
AB  - The uncoupling protein UCP1 aids the production of heat by uncoupling respiration
      from oxidative phosphorylation in brown fat of rodents. UCP1 is down-regulated
      during starvation to conserve energy. Levels of other uncoupling proteins named
      UCP2 and UCP3, which are present in skeletal muscle, increase during starvation
      without changing heat production. Transgenic mice ectopically over-expressing
      UCP3 lost weight and had less adipose tissue than controls, although they were
      hyperphagic. It was proposed that muscle UCP3 regulated fat oxidation rather than
      thermogenesis.

PMID- 11310778
TI  - Remember when mom wanted you home for dinner?
AB  - Limited information exists about the relationship between family dinner and the
      quality of children's diets. However, several studies suggest that foods obtained
      at home have more fiber, calcium, and iron, and less total fat, saturated fat,
      cholesterol, and sodium than foods obtained away from home. The results of a
      recent study confirm and extend these observations by showing beneficial effects
      of family dinner on the diet quality of children ages 9 to 14. Nutritionists and
      health educators should look for ways to encourage families to increase the
      number of meals eaten together to improve the eating patterns of children.

PMID- 11310779
TI  - Principles and applications of luminescence spectroscopy.
AB  - Advances in instrumentation during the last decade as well as the ease with which
      the technology could be adapted to a wide variety of assay platforms has truly
      made luminescence spectroscopy the analytical method of choice in several diverse
      disciplines of life sciences. The primary reasons for its growing popularity are
      twofold: the use of nonisotopic labels and its exquisite sensitivity. Analyte
      concentrations as low as 10(-10) to 10(-12) M can be easily detected, while
      luminometry can detect biological events at concentrations as low as 10(-18) M.
      This is in contrast to absorption and NMR spectroscopic techniques, which
      require, respectively, 10(-8) M and 10(-5) M concentrations of the compound of
      interest. Furthermore, in several variations of this technology, the measurement
      itself can be nondestructive and noninvasive. Despite the fact that luminescence
      spectroscopic techniques provide some of the most sensitive and selective
      analytical methods, they have not yet been widely used in both basic and applied
      food research. The only exception to this is the growing popularity of the
      commercially available ATP bioluminescence kits used routinely for monitoring the
      cleanliness of work surfaces in the food industry. This review describes some of
      the relevant basic aspects of luminescence, several popular variations of this
      technology, and their potential uses in food research.

PMID- 11310780
TI  - Predicting the responses of mechanoreceptor neurons to physiological inputs by
      nonlinear system identification.
AB  - The nonlinear dynamic properties of action potential encoding were studied in
      mechanosensory neurons innervating the slits of a slit-sense organ in the
      tropical wandering spider, Cupiennius salei. The organ contains two types of
      neurons that are morphologically similar but have different dynamic properties.
      Type A neurons produce only one or two action potentials in response to a
      mechanical or electrical stimulus of any suprathreshold amplitude, while type B
      neurons can fire prolonged bursts of action potentials in response to similar
      stimuli. Neurons were stimulated with pseudorandomly modulated intracellular
      current while recording the resultant fluctuations in membrane potential and
      action potentials. A parallel cascade method was used to estimate a third-order
      Volterra series to describe the nonlinear dynamic relationship between membrane
      potential and action potentials. Kernels measured for the two types of neurons
      had reproducible forms that showed differences between the two neuron types. The
      measured kernels were able to predict the responses of the neurons to novel
      pseudorandomly modulated inputs with reasonable fidelity. However, the Volterra
      series did not adequately predict the difference in responses to step
      depolarizations.

PMID- 11310781
TI  - Electrical stimulation of the auditory nerve: single neuron strength-duration
      functions in deafened animals.
AB  - Destruction of cochlear hair cells initiates degenerative changes within auditory
      nerve fibres (ANFs), including loss of peripheral processes and demyelination of
      the cell body. These changes are likely to affect the biophysical processes
      involved in action potential generation to an electrical stimulus. We measured
      the strength-duration relationship in acutely deafened (100% ANF survival) versus
      long-term deafened cochleae (approximately 15% ANF survival) by recording from
      single neurons in the central nucleus of the inferior colliculus (ICC).
      Input/output functions were constructed for 22 ICC neurons in response to
      stimulation of the auditory nerve using biphasic current pulses of 20-1000
      micros/phase. Strength-duration curves were derived and found to be of the same
      general form for both acute and long-term deafened cochleae. While there was an
      increase in rheobase for neurons from long-term versus acute deafened cochleae,
      this increase was not statistically significant (p=0.097). In contrast, chronaxie
      -which is related to the membrane time constant--was significantly shorter in the
      long-term deafened cochleae (p = 0.004). This presumably reflects a shift in the
      site of action potential initiation to the larger diameter, heavily myelinated
      central axon as a result of the pathology. These changes in the site of action
      potential generation have implications for the delivery of charge to ANFs via
      cochlear implants.

PMID- 11310782
TI  - Spatial filter approach for evaluation of the surface Laplacian of the
      electroencephalogram and magnetoencephalogram.
AB  - The surface Laplacian is a technique that has been utilized to improve the
      spatial resolution of the electroencephalogram (EEG) and the magnetoencephalogram
      (MEG). We investigate the amount of improvement to the spatial resolution
      afforded by the surface Laplacian by examining the spatial filters that describe
      the relationship between cortical current sources and the surface Laplacian. The
      surface Laplacian spatial filters extend into higher spatial frequencies than do
      raw signal spatial filters, particularly for EEG Laplacian spatial filters,
      indicating that substantial improvement in spatial resolution is possible.
      However, the response of the surface Laplacian operation to the nature and amount
      of noise in the raw EEG and MEG signals is of paramount importance. Spatially
      correlated noise, coupled with uncorrelated noise, requires additional
      regularization of inverse spatial filters resulting in a decrease in spatial
      resolution. Substantial improvements in spatial resolution may be obtained using
      the surface Laplacian techniques as long as correlated noise levels are small and
      raw signals have relatively high signal-to-noise ratios.

PMID- 11310783
TI  - Spatial filter approach for comparison of the forward and inverse problems of
      electroencephalography and magnetoencephalography.
AB  - We present an analysis of the relative information content of cortical current
      source reconstructions from electroencephalogram (EEG) and magnetoencephalogram
      (MEG) forward calculations by examining the spatial filters that relate the
      internal sources with the externally measured electric potentials and magnetic
      fields. The forward spatial filters are seen to be low-pass functions of spatial
      frequency and spatial resolution degrades in external measurements. Inverse
      spatial filters may be used to reconstruct cortical sources from external data,
      but since they are high-pass functions of spatial frequency, they must be
      regularized to avoid instabilities caused by noise at higher spatial frequencies.
      The regularization process limits the spatial resolution of source
      reconstructions. EEG forward spatial filters fall off at lower spatial
      frequencies than MEG filters; hence, there is less information available in
      higher spatial frequencies resulting in lower spatial resolution in inverse
      reconstructions. The tangential component of the magnetic field provides even
      higher spatial resolution than can be obtained using the radial component. An
      accompanying article examines the surface Laplacian for both the EEG and the MEG.

PMID- 11310784
TI  - Finite element analysis of the current-density and electric field generated by
      metal microelectrodes.
AB  - Electrical stimulation via implanted microelectrodes permits excitation of small,
      highly localized populations of neurons, and allows access to features of
      neuronal organization that are not accessible with larger electrodes implanted on
      the surface of the brain or spinal cord. As a result there are a wide range of
      potential applications for the use of microelectrodes in neural engineering.
      However, little is known about the current-density and electric field generated
      by microelectrodes. The objectives of this project were to answer three
      fundamental questions regarding electrical stimulation with metal microelectrodes
      using geometrically and electrically accurate finite elements models. First, what
      is the spatial distribution of the current density over the surface of the
      electrode? Second, how do alterations in the electrode geometry effect neural
      excitation? Third, under what conditions can an electrode of finite size be
      modeled as a point source? Analysis of the models showed that the current density
      was concentrated at the tip of the microelectrode and at the electrode-insulation
      interface. Changing the surface area of the electrode, radius of curvature of the
      electrode tip, or applying a resistive coating to the electrode surface altered
      the current-density distribution on the surface of the electrode. Changes in the
      electrode geometry had little effect on neural excitation patterns, and modeling
      the electric field generated by sharply tipped microelectrodes using a
      theoretical point source was valid for distances > approximately 50 microm from
      the electrode tip. The results of this study suggest that a nearly uniform
      current-density distribution along the surface of the electrode can be achieved
      using a relatively large surface area electrode (500-1000 microm2), with a
      relatively blunt tip (3-6 microm radius of curvature), in combination with a thin
      (approximately 1 microm) moderately resistive coating (approximately 50 omega m).

PMID- 11310785
TI  - Removal of cardiac beat artifact in esophageal pressure measurement via a
      modified adaptive noise cancellation scheme.
AB  - Information on volume-pressure relationships of human lungs is usually based on
      indirect determination of intrapleural pressure (P(ip)) obtained from the
      esophagus. Unfortunately, cardiac beat artifact frequently corrupts measurement
      of esophageal pressure (P(es)). In this study, we presented a modified adaptive
      noise cancellation (MANC) scheme for removing the cardiac beat artifact in the
      P(es) signal. The proposed methodology used an airflow signal as the reference
      signal with least-mean-square method as the adaptive algorithm. The results of
      six experiments on two Brown-Norway rats showed a significant reduction of the
      apparent cardiac pulsation with minimal distortion of the P(es) signal. The MANC
      filter also showed evidence of peak suppression at integer multiples of heart
      rate in the fast Fourier transform of the P(es) signal while leaving the
      remaining spectrum largely unperturbed. A t-test method and the ratio of standard
      deviation to mean (std/mean) statistics of airway resistance (R(aw)) values were
      used to evaluate the performance of the MANC filter. In all six experiments, a
      reduction of std/mean of R(aw) by 12.5%-68% was obtained, indicating the
      effectiveness of the proposed scheme.

PMID- 11310786
TI  - Elastance-based control of a mock circulatory system.
AB  - A new control strategy for a mock circulatory system (MCS) has been developed to
      mimic the Starling response of the natural heart. The control scheme is based on
      Suga's elastance model, which is implemented using nested elastance and pressure
      feedback control systems. The elastance control loop calculates the desired
      chamber pressure using a time-varying elastance function and the ventricular
      chamber volume signal. The pressure control loop regulates the chamber pressure
      according to this reference signal. Simulations and tests on MCS hardware showed
      that the elastance-based controller responds to changes in preload, afterload,
      and contractility in a manner similar to the natural heart. Since the elastance
      function is an arbitrary function of time, the controller allows modification of
      ventricular chamber contractility, giving researchers a new tool to mimic various
      pathological conditions which can be used in the evaluation of cardiac devices
      such as ventricular assist devices.

PMID- 11310787
TI  - Lung area--volume models in relation to the recruitment--derecruitment of
      individual lung units.
AB  - The objective of this study was to reconsider some of the previous experimental
      results in terms of simple geometric models in order to determine if any of the
      apparent conflicts could be explained within a more unified concept. These models
      allow individual lung units and the entire lung to expand differently with regard
      to their area-volume relationship. The effect of a recruitment-derecruitment
      process as the lung inflates-deflates is also considered. Examples are used to
      illustrate how some of the apparent conflicts found in the literature may arise
      from whether or not recruitment and derecruitment take place during lung
      expansion and contraction.

PMID- 11310788
TI  - Evaluation of a deformable musculoskeletal model for estimating muscle-tendon
      lengths during crouch gait.
AB  - The hamstrings and psoas muscles are often lengthened surgically in an attempt to
      correct crouch gait in persons with cerebral palsy. The purpose of this study was
      to determine if, and under what conditions, medial hamstrings and psoas lengths
      estimated with a "deformable" musculoskeletal model accurately characterize the
      lengths of the muscles during walking in individuals with crouch gait. Computer
      models of four subjects with crouch gait were developed from magnetic resonance
      (MR) images. These models were used in conjunction with the subjects' measured
      gait kinematics to calculate the muscle-tendon lengths at the body positions
      corresponding to walking. The lengths calculated with the MR-based models were
      normalized and were compared to the lengths estimated using a deformable generic
      model. The deformable model was either left undeformed and unscaled, or was
      deformed or scaled to more closely approximate the femoral geometry or bone
      dimensions of each subject. In most cases, differences between the normalized
      lengths of the medial hamstrings computed with the deformable and MR-based models
      were less than 5 mm. Differences in the psoas lengths computed with the
      deformable and MR-based models were also small (<3 mm) when the deformable model
      was adjusted to represent the femoral geometry of each subject. This work
      demonstrates that a deformable musculoskeletal model, in combination with a few
      subject-specific parameters and simple normalization techniques, can provide
      rapid and accurate estimates of medial hamstrings and psoas lengths in persons
      with neuromuscular disorders.

PMID- 11310789
TI  - Possible involvement of ERK 1/2 in UVA-induced melanogenesis in cultured normal
      human epidermal melanocytes.
AB  - UV-induced melanogenesis is a well known physiological response of human skin
      exposed to solar radiation; however, the signaling molecules involved in the
      stimulation of melanogenesis in melanocytes following UV exposure remain unclear.
      In this study we induced melanogenesis in vitro in normal human epidermal
      melanocytes using a single irradiation with UVA at 1 kJ/m2 and examined the
      potential involvement of mitogen-activated protein kinases (MAPK) as UVA
      responsive signaling molecules in those cells. UVA irradiation did not affect the
      proliferation of melanocytes, but it did increase tyrosinase mRNA expression,
      which reached a maximum level 4 hr after UVA irradiation. The amount of
      tyrosinase protein, as quantitated by immunoblotting, was also increased at 24 hr
      following UVA irradiation. Among the MAPK examined, extracellular signal-related
      kinase (ERK) 1/2 was phosphorylated within 15 min of UVA irradiation, but no such
      phosphorylation was observed for c-Jun N-terminal kinases (JNK) or p38.
      Accordingly, the activity of ERK1/2 was also increased shortly after UVA
      irradiation. These responses of ERK1/2 to UVA irradiation were markedly inhibited
      when cells were pre-treated with N-acetyl-L-cysteine, an antioxidant, or with
      suramin, a tyrosine kinase receptor inhibitor. The formation of (6
      4)photoproducts or cyclobutane pyrimidine dimers was not detected in cellular DNA
      after UVA irradiation. These findings suggest that a single UVA irradiation
      induced melanogenesis is associated with the activation of ERK1/2 by upstream
      signals that originate from reactive oxygen species or from activated tyrosine
      kinase receptors, but not from damaged DNA.

PMID- 11310790
TI  - Ceramide inhibits cell proliferation through Akt/PKB inactivation and decreases
      melanin synthesis in Mel-Ab cells.
AB  - Ceramide is a bioactive sphingolipid that mediates a variety of cell functions.
      However, the effects of ceramide on cell growth and the melanogenesis of
      melanocytes are not known. In the present study, we investigated the actions of
      cell-permeable ceramide and its possible role in the signaling pathway of a
      spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show
      that C2-ceramide inhibits DNA synthesis in Mel-Ab cells and G361 human melanoma
      cells in a dose-dependent manner. Cell cycle analysis confirmed the inhibition of
      DNA synthesis by a reduction in the S phase. To investigate the ceramide
      signaling pathway, we studied whether C2-ceramide is able to influence
      extracellular signal-regulated kinase (ERK) and/or Akt/protein kinase B (PKB)
      activation. We demonstrated that phosphorylated Akt/PKB is decreased by C2
      ceramide, whereas phosphorylated ERK was only slightly affected. Therefore, the
      C2-ceramide-induced inactivation of Akt/PKB may be closely related to the reduced
      cell proliferation of Mel-Ab cells. Furthermore, we assessed the effects of C2
      ceramide on the pigmentation of Mel-Ab cells. The results obtained showed that
      the melanin content of cells was significantly reduced by C2-ceramide at
      concentrations in the range of 1-10 microM, and that the pigmentation-inhibiting
      effect of C2-ceramide is much greater than that of kojic acid at 1-100 microM. In
      addition, we found that the activity of tyrosinase is reduced by C2-ceramide
      treatment. Our results demonstrate that C2-ceramide reduces the pigmentation of
      Mel-Ab cells by inhibiting tyrosinase activity.

PMID- 11310791
TI  - Keratinocytes suppress TRP-1 expression and reduce cell number of co-cultured
      melanocytes - implications for grafting of patients with vitiligo.
AB  - A pilot study for grafting of patients with vitiligo using cultured epithelial
      autografts containing melanocytes gave disappointing clinical results, with
      pigmentation achieved in only one out of five patients. Irrespective of the fate
      of melanocytes grafted back onto the patients, we experienced problems in
      identifying melanocytes within these well-integrated keratinocyte sheets. This
      led us to explore the fate of these cells within these sheets in vitro and to
      seek to improve their number and function within the sheets. We report that the
      introduction of a fibroblast feeder layer can improve melanocyte number within
      melanocyte/keratinocyte co-cultures initially, but at very high keratinocyte
      density, there is a marked loss of melanocytes (as detected by staining for
      S100). Additionally, we found that keratinocytes not only down-regulate
      melanocyte number, but also pigmentary function; thus, it was possible to
      identify melanocytes that were S100 positive but tyrosinase-related protein-1
      (TRP-1) negative in confluent well-integrated keratinocyte sheets. In summary,
      our data suggest that keratinocytes at high density initially suppress melanocyte
      pigmentation (as evidenced by a lack of TRP-1 expression) and then cause a
      physical loss of melanocytes. The introduction of a fibroblast feeder layer can
      help maintain melanocyte number while keratinocytes are subconfluent, but fails
      to oppose the inhibitory influence of the keratinocytes on melanocyte TRP-1
      expression.

PMID- 11310792
TI  - Melanosynthesis, differentiation, and apoptosis in Kupffer cells from Rana
      esculenta.
AB  - It is well known that amphibian Kupffer cells (KCs) contain eumelanins. In this
      paper, we demonstrate through a molecular analysis that Rana esculenta KCs
      synthesize high levels of mRNA for tyrosinase and through cytochemistry that they
      possess dopa oxidase activity: both these data prove that frog KCs are capable of
      autonomously synthesizing eumelanins. On the other hand, by using a highly
      sensitive reverse transcription-polymerase chain reaction assay we clearly show
      that in mammalian KCs the tyrosinase gene is not expressed. Quite unexpectedly,
      we have detected tyrosinase mRNA in Rana esculenta spleen, lung, and heart; to
      explain this finding, we suggest that it could be due to the presence of
      pigmented macrophages within the spleen, that probably behave as KCs, and of
      melanophores in lung and heart. It also may be hypothesized that the Rana
      esculenta tyrosinase gene, as opposed to its mammalian counterpart, is expressed
      in many cell types because its promoter contains sequences that are recognized by
      widely synthesized transcription factors. Our experiments also demonstrate that
      there is an inverse correlation between the amount of tyrosinase mRNA and melanin
      content, and that populations of terminally differentiated KCs are characterized
      by a high degree of apoptosis. Based on these data, we propose that
      differentiating KCs start accumulating eumelanins, as a result of previous
      expression of high levels of tyrosinase and of dopa oxidase activity, acquire the
      full KC phenotype (characterized by both phagocytic and melanosynthetic ability),
      and then undergo apoptosis. Accordingly, we propose that these cells could
      represent an interesting model to study, at the molecular level, the relationship
      between differentiation, specific gene expression, and programmed cell death in
      higher eukaryotes.

PMID- 11310793
TI  - Regulation of tyrosinase-related protein-2 (TYRP2) in human melanocytes:
      relationship to growth and morphology.
AB  - Treatment of human melanoma cells with the differentiation-inducing agent
      hexamethylene bisacetamide (HMBA) results in reciprocal changes in expression of
      melanocyte-specific genes tyrosinase-related proteins-1 and -2 (TYRP1 and TYRP2).
      In this study, we investigated the effects of HMBA on cultured neonatal human
      cutaneous melanocytes. Flow cytometric analysis showed that HMBA inhibited 12-O
      tetradecanoylphorbol-13-acetate (TPA)-dependent growth of melanocytes by reducing
      the population of cells entering the DNA synthesis phase of cell cycle.
      Melanocyte growth inhibition was accompanied by an increase in the number of
      cells exhibiting polydendritic morphology. This morphologic change was less
      pronounced when HMBA was added to melanocytes in the absence of TPA. Northern
      blot analyses of total cellular RNA showed that expression of microphthalmia
      associated transcription factor (MITF), tyrosinase (TYR), TYRP1, Silver
      (SILV/Pmel17) gene was down-regulated by HMBA, while TYRP2 mRNA was up-regulated
      (> 10-fold). When the inducer was added to cells in the absence of TPA, there was
      > 50-fold increase in TYRP2 mRNA with a moderate increase in MITF, tyrosinase and
      SILV gene mRNAs and complete repression of TYRP1 gene. Studies using inhibitors
      for protein kinases involved in cell signaling pathways suggested that stress
      activated kinase p38 and mitogen-activated protein kinase kinase MEK are involved
      in TPA-independent regulation of TYRP2 expression in melanocytes. These data show
      that treatment of proliferating melanocytes with the differentiation inducer HMBA
      results in a distinct change in morphology and up-regulation of TYRP2, while
      quiescent melanocytes respond by a dramatic increase in expression of TYRP2
      without change in morphology. These results suggest an inverse relationship of
      TYRP2 gene regulatory mechanisms to melanocyte growth regulatory pathways.

PMID- 11310794
TI  - Aberrant expression of MSG1 transcriptional activator in human malignant melanoma
      in vivo.
AB  - MSG1 was originally isolated as a candidate pigmentation-related gene. MSG1 mRNA
      transcripts were expressed strongly in cultured human and mouse normal epidermal
      melanocytes, and in highly pigmented mouse melanoma cells, while its expression
      was very weak in cultured non-pigmented human melanoma cells. Thus, MSG1 was
      initially proposed to be a melanocyte-specific gene, and its possible role in
      pigmentation has been speculated. It was found recently that the MSG1 protein
      interacts functionally with Smad4, which plays a pivotal role in signal
      transduction of transforming growth factor-beta. In this study, we analyzed MSG1
      protein expression by immunohistochemistry using human tumor samples from nevus
      and malignant melanoma to reveal its role in pigmentation and melanoma
      development in vivo. A relatively strong but heterogeneous expression of MSG1
      protein was seen in melanomas compared with weak expression in nevi. In nevi,
      MSG1 expression was mostly confined to the pigmented region, while it was
      expressed in both pigmented and non-pigmented regions in melanoma.
      Intracellularly, MSG1 protein was localized in the cytoplasm of nevus cells, but
      was seen in both nuclei and cytoplasm of melanoma cells. These results support a
      hypothesis that MSG1 plays a role in pigmentation. It is also suggested that MSG1
      may be involved in malignant transformation of pigment cells. Alternatively, the
      aberrant expression of MSG1 in melanoma cells might be due to the abnormal
      environment, including aberrant cytokine or growth factor expression, associated
      with melanoma formation.

PMID- 11310795
TI  - Gene regulation in melanoma progression by the AP-2 transcription factor.
AB  - The molecular changes associated with the transition of melanoma cells from
      radial growth phase (RGP) to vertical growth phase [(VGP), metastatic phenotype]
      are not very well defined. We previously demonstrated that expression of the cell
      surface adhesion molecule MCAM/MUC18 correlates directly with the metastatic
      potential of human melanoma cells. In addition, the progression of human melanoma
      towards the metastatic phenotype is associated with loss of expression of the
      tyrosine-kinase receptor c-KIT. In this review, I will summarize our recent
      studies demonstrating that the expression of both genes is regulated by the AP-2
      transcription factor. Moreover, we have observed a loss of AP-2 expression in
      metastatic melanoma cells. Re-expression of AP-2 in the highly metastatic A375SM
      cells decreased their tumorigenicity and inhibited their metastatic potential in
      nude mice. MCAM/MUC18 mRNA and protein expression was significantly down
      regulated while c-KIT expression was up-regulated in the AP-2-transfected cells.
      To further investigate the role of AP-2 in the progression of human melanoma, we
      attempted to inactivate AP-2 in primary cutaneous melanoma by using a dominant
      negative AP-2, or the AP-2B gene. Expression of AP-2B in SB-2 cells augmented
      their tumorigenicity in nude mice, and upregulated MMP-2 expression and activity.
      As AP-2 also regulates other genes that are involved in the progression of human
      melanoma such as E-cadherin, p21/WAF-1, HER2/neu, Bcl-2, FAS/APO-1, IGF-R-1, VEGF
      and the thrombin receptor (PAR-1), we therefore propose that loss of AP-2 is a
      crucial event in the development of malignant melanoma. In addition, the
      transition of melanoma cells from RGP to VGP is also associated with over
      expression of the transcription factors CREB and ATF-1. The notion that the
      balance between AP-2 and CREB/ATF-1 expression determines the progression of
      melanoma cells towards the metastatic phenotype will be discussed.

PMID- 11310796
TI  - The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type
      2 (OCA2), and melanosomal pH.
AB  - Recessive mutations of the mouse p (pink-eyed dilution) gene lead to
      hypopigmentation of the eyes, skin, and fur. Mice lacking a functional p protein
      have pink eyes and light gray fur (if non-agouti) or cream-colored fur (if
      agouti). The human orthologue is the P protein. Humans lacking a functional P
      protein have oculocutaneous albinism type 2 (OCA2). Melanocytes from p-deficient
      mice or OCA2 individuals contain small, minimally pigmented melanosomes. The
      mouse and human proteins are predicted to have 12 membrane spanning domains and
      possess significant sequence homology to a number of membrane transport proteins,
      some of which are involved in the transport of anions. The p protein has been
      localized to the melanosome membrane. Recently, it has been shown that
      melanosomes from p protein-deficient melanocytes have an abnormal pH. Melanosomes
      in cultured melanocytes derived from wild-type mice are typically acidic, whereas
      melanosomes from p protein-deficient mice are non-acidic. Melanosomes and related
      endosome-derived organelles (i.e., lysosomes) are thought to have an adenosine
      triphosphate (ATP)-driven proton pump that helps to generate an acidic lumen. To
      compensate for the charge of these protons, anions must also be transported to
      the lumen of the melanosome. In light of these observations, a model of p protein
      function is presented in which the p protein, together with the ATP-driven proton
      pump, regulates the pH of the melanosome.

PMID- 11310797
TI  - Quantitation and visualization of ultraviolet-induced DNA damage using specific
      antibodies: application to pigment cell biology.
AB  - The major types of DNA damage induced by sunlight in the skin are DNA
      photoproducts, such as cyclobutane pyrimidine dimers (CPDs), (6-4)photoproducts
      (6-4PPs) and Dewar isomers of 6-4PPs. A sensitive method for quantitating and
      visualizing each type of DNA photoproduct induced by biologically relevant doses
      of ultraviolet (UV) or sunlight is essential to characterize DNA photoproducts
      and their biological effects. We have established monoclonal antibodies specific
      for CPDs, 6-4PPs or Dewar isomers. Those antibodies allow one to quantitate
      photoproducts in DNA purified from cultured cells or from the skin epidermis
      using an enzyme-linked immunosorbent assay. One can also use those specific
      antibodies with in situ laser cytometry to visualize and measure DNA
      photoproducts in cultured cells or in the skin, using indirect immunofluorescence
      and a laser-scanning confocal microscope. This latter method allows us to
      reconstruct three-dimensional images of nuclei containing DNA photoproducts and
      to simultaneously examine DNA photoproducts and histology in multilayered
      epidermis. Using those techniques, one can determine the induction and repair of
      these three distinct types of DNA photoproducts in cultured cells and in the skin
      exposed to sublethal or suberythematous doses of UV or solar simulated radiation.
      As examples of the utility of these techniques and antibodies, we describe the
      DNA repair kinetics following irradiation of human cell nuclei and the
      photoprotective effect of melanin against DNA photoproducts in cultured pigmented
      cells and in human epidermis.

PMID- 11310798
TI  - Sequence analysis of dru regions from methicillin-resistant Staphylococcus aureus
      and coagulase-negative staphylococcal isolates.
AB  - Methicillin-resistance in staphylococci results from expression of mecA, which
      occurs in a larger region of DNA (the mec region) lacking counterpart in
      susceptible cells. The mec region harbors in addition a highly polymorphic
      element, the dru (direct repeat unit) segment, which in an early S. aureus
      strain, BB270, was found to contain 10 imperfect 40 base-pair repeats. We have
      explored the utility of direct sequencing of dru segments for discriminating
      among strains of methicillin-resistant S. aureus (MRSA) and coagulase-negative
      staphylococci (MRCNS). We sequenced dru segments of 24 clinical isolates of MRSA,
      and 15 of MRCNS, and reexamined strain BB270. Six S. aureus and 2 S. epidermidis
      isolates were found to have deletions which removed all drus. The other strains
      were found to have multiple contiguous dru repeats of precisely 40 bp. Analysis
      of these strains plus dru segment sequence from 4 recent reports yielded 18
      unique dru segment sequences (designated "dru types") differing in numbers of
      repeats and/or sequences of particular repeats. Dru typing was more
      discriminating than sequencing of non-mec region genes, including a repeat
      containing segment (spa Xr) of the S. aureus protein A gene. Yet dru type was
      sufficiently stable to register epidemiological clusters. Dru sequencing is a
      useful tool for tracking methicillin-resistant lineages of S. aureus and CNS.

PMID- 11310799
TI  - Variation in clonality and antibiotic-resistance genes among multiresistant
      Salmonella enterica serotype typhimurium phage-type U302 (MR U302) from humans,
      animals, and foods.
AB  - Since 1990 multiresistant (MR) Salmonella enterica serotype Typhimurium
      definitive phage-type (DT) 104 (MR DT104) and closely related phage types have
      emerged as a worldwide health problem in humans and food animals. In this study
      the presence of the blaCARB-2 (ampicillin), cmlA (chloramphenicol), aadA2
      (streptomycin/spectinomycin), sul1 (sulphonamide), and tetG (tetracycline)
      resistance genes in isolates of one such phage type, U302, have been determined.
      In addition blaTEM primers have been used for the detection of TEM-type beta
      lactamases. Isolates have also been characterized by plasmid profile and pulsed
      field gel electrophoresis (PFGE). Thirty-three of 39 isolates were positive for
      blaCARB-2, cmlA, aadA2, sul1 and tetG, four for blaTEM, aadA2 and sul1, one for
      aadA2 and sul1, and one for blaTEM only. blaTEM-mediated ampicillin resistance
      was transferred to Escherichia coli K12 from three isolates along with other
      resistance markers, including resistance to chloramphenicol, streptomycin,
      spectinomycin, sulphonamides, and tetracyclines. Strains carried up to 6 plasmids
      and 34 plasmid profiles were identified. Although the majority of strains (33/39)
      produced a PFGE profile identical to that predominant in MR DT104, six different
      patterns were generated demonstrating the presence of various clones within MR
      U302. The results show that the majority of the MR U302 strains studied possessed
      the same antibiotic resistance genes as MR DT104. However, isolates with
      distinctive PFGE patterns can have different mechanisms of resistance to
      ampicillin, chloramphenicol, streptomycin, sulphonamides, and tetracyclines. Such
      resistance genes may be borne on transmissible plasmids.

PMID- 11310800
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in
      Colombian hospitals: dominance of a single unique multidrug-resistant clone.
AB  - The first study on the molecular characterization of methicillin-resistant
      Staphylococcus aureus (MRSA) isolates from Colombia was performed as part of a
      global surveillance established by the CEM/NET Initiative, under Project RESIST.
      Seventy-six MRSA isolates recovered from five hospitals during 1996-1998 were
      analyzed by the hybridization of ClaI restriction digests with mecA- and Tn554
      specific probes, and by pulsed-field gel electrophoresis (PFGE) of chromosomal
      SmaI digests. All MRSA isolates, with one exception, belonged to a single clonal
      type II::NH::D. This clone, which was previously described among MRSA isolates
      recovered in the early 1990s in European and New York and South American
      hospitals, showed resistance to beta-lactam antibiotics only and appeared to be
      associated almost exclusively with pediatric infections ("Pediatric clone" of
      MRSA). While sharing identical molecular typing properties with the Pediatric
      clone, the Colombian isolates differed by extensive multidrug resistance and were
      recovered from patients of all ages. It is also noteworthy that the Brazilian
      clone of MRSA (XI::B::B), another multidrug-resistant international clone
      currently widely spread in Brazil, Argentina, Uruguay, Chile, and also in several
      European countries, was completely absent from this set of isolates from
      Colombia.

PMID- 11310801
TI  - A multicenter study of the antimicrobial susceptibility of Haemophilus
      influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis isolated from
      patients with community-acquired lower respiratory tract infections in 1999 in
      Portugal.
AB  - A nationwide multicenter study (including 25 laboratories) of the antimicrobial
      susceptibility of bacterial pathogens commonly associated with community-acquired
      lower respiratory tract infections (LRTI), with testing undertaken in a central
      laboratory, was conducted in Portugal in 1999. Antimicrobial resistance in
      Haemophilus influenzae has not increased in the last decade. Of the 498 isolates
      tested, 12.4% produced beta-lactamase and >95% were susceptible to all
      antimicrobials except ampicillin. In contrast, there was a rapid increase of
      resistance in Streptococcus pneumoniae. Of the 312 isolates tested, 24.7%
      exhibited decreased susceptibility to penicillin (13.5% showed low-level and
      11.2% high-level resistance), 13.8% were resistant to erythromycin,
      clarithromycin and azithromycin, and 13.6% to cefuroxime and to tetracycline. Of
      the 38 Moraxella catarrhalis tested, 81.6% produced beta-lactamase. Resistance to
      penicillin, cefuroxime, erythromycin, clarithromycin, and azithromycin in S.
      pneumoniae and beta-lactamase production in H. influenzae were significantly
      higher in pediatric patients than in adults. Overall, amoxycillin/clavulanate was
      the most active antimicrobial agent in vitro against H. influenzae, S.
      pneumoniae, and M. catarrhalis isolated from patients with community-acquired
      LRTI in Portugal.

PMID- 11310802
TI  - In vitro activity of 19 antimicrobial agents against enterococci from healthy
      subjects and hospitalized patients and use of an ace gene probe from Enterococcus
      faecalis for species identification.
AB  - We tested 165 enterococcal isolates, biased toward vancomycin resistant (VR)
      isolates, collected during recent years from fecal samples of healthy subjects
      and clinical specimens of hospitalized patients (mostly from United States and
      some from Europe) for susceptibility to 19 antimicrobials. Nosocomial isolates,
      whether VR or not, were more often highly resistant to aminoglycosides and
      clindamycin than fecal isolates from healthy community volunteers and more often
      resistant to erythromycin, chloramphenicol, trimethoprim, levofloxacin and, for
      E. faecium, ampicillin (93 vs. 0%). Resistance rates were similar between
      nosocomial and community-fecal isolates for minocycline, rifampin and
      quinupristin-dalfopristin (Q-D). None of the 165 enterococci tested hybridized
      with aph(2'')-Ic and aph(2'')-Id probes for recently described gentamicin
      resistance genes and 37 of the 39 isolates with high level resistance (HLR) to
      gentamicin hybridized with an intragenic aac(6')-aph(2'') probe. Of the two newer
      drugs tested, daptomycin MIC90s were 0.25 microg/mL for E. faecalis and 1
      microg/mL for E. faecium, regardless of their vancomycin resistance level or
      source. For Q-D, none of 28 E. faecium from community based healthy subjects in
      the USA and 7 of 66 E. faecium from hospitalized patients in the United States
      were resistant. Among these 7 Q-Dr United States isolates and 7 Q-Dr isolates
      from Europe (MICs of Q-D of 4-8 microg/mL), none hybridized with vat(D) (formerly
      satA) and vat(E) (formerly satG) DNA probes, indicating the involvement of other
      mechanism/s of resistance in these isolates. We also demonstrated that an
      intragenic probe of the gene ace from E. faecalis showed specific hybridizations
      to all E. faecalis isolates, suggesting the usefulness of this gene for
      identification of this species.

PMID- 11310803
TI  - Molecular epidemiology and mutations at gyrA and parC genes of ciprofloxacin
      resistant Escherichia coli isolates from a Taiwan medical center.
AB  - Sixty-five ciprofloxacin-resistant clinical Escherichia coli isolates were
      collected from a Taiwan Medical Center from December 1998 to February 1999. All
      65 clinical isolates were resistant (MICs > or = 4 microg/mL) to the following
      fluoroquinolones: ofloxacin, levofloxacin, sparfloxacin, and trovafloxacin. These
      isolates were cross-resistant to chloramphenicol (65 isolates, 100%),
      tetracycline (65 isolates, 100%), cefuroxime (64 isolates, 98.5%), ampicillin (57
      isolates, 87.7%), gentamicin (53 isolates, 81.5%), and cephalothin (24 isolates,
      36.9%). Pulsed-field gel electrophoresis (PFGE) revealed a high diversity among
      the genomes of these isolates and indicated that clonal spread was not
      responsible for the prevalence of ciprofloxacin resistance in the hospital.
      Sequencing of the polymerase chain reaction (PCR) amplified products of the
      quinolone resistance determining regions (QRDRs) of gyrA and parC showed that all
      isolates carrying double mutations in gyrA at codon 83 and 87 and at least one
      parC mutation at codon 80 and/or 84. The mutation at codon 83 of GyrA from serine
      to leucine (S83L) was present in all the clinical isolates. The most prevalent
      pattern was the S83L mutation and the mutation at codon 87 from an aspartate to
      an asparagine (D87N) of GyrA plus a mutation from a serine to an isoleucine
      (S80I) at codon 80 of ParC (63.2%). This indicated that the presence of high
      level resistance to quinolones in clinical E. coli isolates were associated with
      mutations at hot spots, codon 83 and 87 in GyrA and followed by subsequent
      mutation in either codon 80 and/or 84 in ParC.

PMID- 11310804
TI  - Prevalence of serotypes and molecular epidemiology of Streptococcus pneumoniae
      strains isolated from children in Beijing, China: identification of two novel
      multiply-resistant clones.
AB  - Three-hundred and seventy-six strains of Streptococcus pneumoniae isolated from
      clinical specimens and nasopharyngeal swabs from children at daycare centers and
      hospitals in Beijing China, between January 1997 and March 1998, were serotyped.
      Twenty-seven different serotypes were identified. The most prevalent serotypes in
      the carriage isolates were 6A, 19F, 23F, and 15 and were found in 66.8% of cases.
      Serotype data indicate that 51.8% of carrier strains would be included in the 11
      valent conjugate vaccine formulation, while inclusion of vaccine-related
      serotypes, increased the potential vaccine coverage to 79.4%. Serotypes 7, 6B,
      23F, 19F, 15, and 3 accounted for 62% of clinical strains, with 70% vaccine
      related serotypes. DNA fingerprinting of 47 penicillin resistant and 71
      penicillin-susceptible/macrolide-resistant strains by BOX polymerase chain
      reaction (PCR), pulsed-field gel electrophoresis (PFGE), and penicillin binding
      protein (PBP)-fingerprinting identified two novel clones: one a serotype 23F
      multiresistant clone resistant to penicillin, tetracycline, erythromycin,
      clindamycin, and variably resistant to chloramphenicol and trimethoprim
      sulphamethoxazole; and the second a multiresistant penicillin-susceptible,
      macrolide-resistant serotype 6A clone, highly resistant also to tetracycline,
      clindamycin, and trimethoprim-sulphamethoxazole. The macrolide resistance
      determinant in 89% of erythromycin-resistant strains tested (penicillin
      susceptible and penicillin-resistant) was the erm gene, both the erm and mef
      genes were simultaneously found in 6%, and mef alone in 3.4%. The data
      demonstrates that macrolide resistant strains in China include clonal strains and
      strains with dual mef and erm resistance determinants.

PMID- 11310805
TI  - SmaI macrorestriction analysis of Italian isolates of erythromycin-resistant
      Streptococcus pyogenes and correlations with macrolide-resistance phenotypes.
AB  - High rates of erythromycin resistance among Streptococcus pyogenes strains have
      been reported in Italy in the last few years. In this study, 370 erythromycin
      resistant (MIC, > or = 1 microg/mL) Italian isolates of this species obtained in
      1997-1998 from throat swabs from symptomatic patients were typed by analyzing
      SmaI macrorestriction fragment patterns by pulsed-field gel electrophoresis
      (PFGE). Among the typable isolates (n = 341; the genomic DNA of the remaining 29
      isolates was not restricted by SmaI), 48 distinct PFGE types were recognized, of
      which 31 were recorded in only one isolate (one-strain types). Fifty-two percent
      of typable isolates fell into three type clusters and 75% into six, suggesting
      that erythromycin-resistant group A streptococci circulating in Italy are
      polyclonal, but the majority of them probably derives from the spread of a
      limited number of clones. In parallel experiments, the 370 test strains were
      characterized for the macrolide resistance phenotype: 80 were assigned to
      phenotype cMLS, 89 to phenotype iMLS-A, 33 to phenotype iMLS-B, 11 to phenotype
      iMLS-C, and 157 to phenotype M. There was a close correlation between these
      phenotypic data and the genotypic results of PFGE analysis, the vast majority of
      the isolates assigned to individual PFGE classes belonging usually to a single
      phenotype of macrolide resistance. All of the 29 untypable isolates belonged to
      the M phenotype. Further correlations were observed with tetracycline resistance.

PMID- 11310806
TI  - Disinfectant and antibiotic resistance of lactic acid bacteria isolated from the
      food industry.
AB  - Quaternary ammonium compounds (QACs) are widely used as disinfectant in medical
      and food environments. There is a growing concern about the increasing incidence
      of disinfectant-resistant microorganisms from food. Disinfectant-resistant lactic
      acid bacteria (LAB) may survive disinfection and cause spoilage problems.
      Moreover, resistant LAB may potentially act as a reservoir for resistance genes.
      A total number of 320 LAB from food industry and meat were screened for
      resistance to the QAC benzalkonium chloride (BC). Out of 320 strains, five
      strains (1.5%) were considered to be resistant and 56 (17.5%) were tolerant to
      BC. The resistant strains were isolated from food processing equipment after
      disinfection. The resistant, tolerant, and some sensitive control bacteria were
      examined for susceptibility to 18 different antibiotics, disinfectants, and dyes
      using disc agar diffusion test and microdilution method. Little systematic cross
      resistance between BC and any of the antimicrobial agents tested were detected
      except for gentamycin and chlorhexidine. A BC-tolerant strain was much easier to
      adapt to higher levels of BC as compared to a BC-sensitive strain. No known gram
      positive QAC resistance genes (qacA/B, qacC, qacG, and qacH) were detected in the
      BC-resistant strains. Identification to species level of the BC-resistant
      isolates was carried out by comparative analysis of 16S-rDNA sequencing. In
      conclusion, resistance to BC is not frequent in LAB isolated from food and food
      environments. Resistance may occur after exposure to BC. The BC resistant
      isolates showed no cross-resistance with other antimicrobial compounds, except
      for gentamycin and chlorhexidine. Nevertheless, BC-resistant LAB may be isolated
      after disinfection and may contribute to the dissemination of resistance.

PMID- 11310808
TI  - Women's work roles and their impact on health, well-being, and career:
      comparisons between the United States, Sweden, and The Netherlands.
AB  - As women have become more assimilated into the work-force over recent decades,
      they have realized considerable changes in their work roles which may contribute
      to health problems and other negative outcomes such as marital strain and
      diminished job status. The purpose of this review was threefold: (1) to
      synthesize data on the distribution of women's work efforts in the areas of paid
      employment, household chores, and childcare; (2) to outline research which
      addresses the impact of women's workload on their well-being and careers; and (3)
      to make international and gender comparisons regarding women's work
      responsibilities. Our findings showed that women from each of the three countries
      examined--the United States, Sweden, and The Netherlands--contribute more effort
      to household chores and childcare and less to the workplace than men do. As a
      result, their total workloads appear to be somewhat greater and more diffusely
      distributed than those of men. Heavy workloads may adversely affect women's
      health, especially in the presence of certain role characteristics (e.g., having
      a clerical, managerial, professional, or executive position, or caring for young
      children). Heavy work responsibilities may also undermine marital happiness,
      particularly if there is perceived inequity in the way partners share household
      work. Finally, women's total work responsibilities often impact their careers due
      to compensatory reductions in work commitment and job status. These observations
      point to the need for further research on women's workload and work roles, on the
      relationship of work to well-being, and on methods of preventing or alleviating
      adverse effects on overburdened workers.

PMID- 11310807
TI  - Usefulness of betalactam therapy for community-acquired pneumonia in the era of
      drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillin
      clavulanate and ceftriaxone.
AB  - Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been
      complicated by the worldwide emergence of penicillin resistance among
      Streptococcus pneumoniae. The impact of this resistance on the outcome of
      patients hospitalized for CAP, empirically treated with betalactams, has not been
      evaluated in a randomized study. We conducted a prospective, randomized trial to
      assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) and ceftriaxone
      (1 g/24 hr) in a cohort of patients hospitalized for moderate-to-severe CAP.
      Three-hundred seventy-eight patients were randomized to receive amoxicillin
      clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed
      on Day 2, after completion of therapy and at long term follow-up. There were no
      significant differences in outcomes between treatment groups, both in intention
      to-treat and per-protocol analysis. Overall mortality was 10.3% for amoxicillin
      clavulanate and 8.8% for ceftriaxone (NS). There were 116 evaluable patients with
      proven pneumococcal pneumonia. Rates of high-level penicillin resistance (MIC of
      penicillin > or = 2 microg/mL) were similar in the two groups (8.2 and 10.2%).
      Clinical efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and
      88.9% for ceftriaxone (95% C.I. of the difference: -9.3 to +12.7%). No
      differences in outcomes were attributable to differences in penicillin
      susceptibility of pneumococcal strains. Sequential i.v./oral amoxicillin
      clavulanate and parenteral ceftriaxone were equally safe and effective for the
      empirical treatment of acute bacterial pneumonia, including penicillin and
      cephalosporin-resistant pneumococcal pneumonia. The use of appropriate
      betalactams in patients with penumococcal pneumonia and in the overall CAP
      population, is reliable at the current level of resistance.

PMID- 11310809
TI  - Perceived risks and reported behaviors associated with osteoporosis and its
      treatment.
AB  - This study investigates older American women's knowledge and risk perceptions
      about osteoporosis and its treatment. Our results indicate that older U.S. women
      undervalue the health impact of osteoporosis; they consider it controllable, and
      neither life threatening nor dreaded relative to other possible diseases or
      conditions. At least 1/3 of older women in a diagnosed and general sample also
      confused osteoporosis with arthritis. Women scored highest on osteoporosis
      knowledge questions related to items under their personal control, such as diet
      or exercise. Further, women who understood the effects of a particular behavior
      on osteoporosis were more likely to act in accordance with that knowledge than
      were women who did not understand those effects.

PMID- 11310810
TI  - Recruiting women into a smoking cessation program: who might quit?
AB  - This article describes women who called a research line to quit smoking and
      identifies correlates of confidence in quitting among the callers. Approximately
      4,000 women called the study line to participate after a single press release,
      indicating intensive interest in quitting. Overall, the randomized sample of
      women was aged 26 to 65 years, reported smoking just over one pack per day, was
      mostly White, predominantly employed, and had quit an average of two times the
      past year before joining the study. Standard background variables, such as age,
      income, body weight and smoking history variables did not predict baseline self
      efficacy or confidence in quitting. However, level of stress, cognitive
      restraint, and weight gain concerns did predict self-efficacy. These data
      indicate strong interest in quitting among women and highlight the role of affect
      and weight concerns in quitting confidence.

PMID- 11310811
TI  - Urinary incontinence, the hidden health problem of Cretan women: report from a
      primary care survey in Greece.
AB  - OBJECTIVE: The prevalence of urine leakage and care-seeking rates of women 35-75
      years of age who visited GPs in two rural areas of Crete were investigated.
      PARTICIPANTS: All the women who visited their family physician in two primary
      care units during the period of August to November 1997 (N = 251) were asked if
      they had experienced symptoms of involuntary urine leakage. A set of questions
      was addressed to the women who replied positively. RESULTS: Sixty-nine of the 251
      women (27.5%) reported symptoms of involuntary urine leakage, and among the
      incontinent women 11 (15.9%) had previously contacted the health services about
      their problem. Only six out of thirty (20%) of the incontinent women who report
      effects on household activities, social and sexual life had contacted a physician
      about urinary incontinence (UI). The most common reason reported for not
      consulting the physicians was that the symptoms were not considered serious (35
      women out of 58, 60.3%). CONCLUSION: This study points out the need for further
      awareness programs for both women and healthcare professionals to be set up in
      countries like Greece, in which a low care-seeking rate of incontinent women has
      been reported.

PMID- 11310812
TI  - Pain and depression experienced by women with interstitial cystitis.
AB  - The goal of this study was to better understand the experience of women suffering
      from interstitial cystitis (IC), a chronic pain condition that has, as of yet,
      received little attention from psychosocial investigators. Eighty women with IC
      participated. The results from this study demonstrate that, in addition to
      frequency of voiding (the hallmark symptom of the disorder), IC sufferers also
      endure significant pain and depression. Levels of pain experienced by IC patients
      during their most painful flares exceed levels of pain experienced by other
      chronic pain patients. Similarly, levels of depression experienced by IC patients
      exceed those evidenced by the general population and by other populations of
      chronic pain patients. Furthermore, the pain and depression experienced by IC
      patients may be predicted by cognitive factors. Severity of pain is associated
      with self-efficacy for coping with pain. Severity of depression is associated
      with pain, self-efficacy for coping with pain, and self-stigmatization.

PMID- 11310813
TI  - High-risk childbirth practices in remote Nepal and their determinants.
AB  - This study describes birth-related practices and their determinants among women
      in the Jumla district of Nepal. Data were derived from a household survey in
      1996. Of 939 married women of reproductive age, 657 who had given birth to their
      last child during the previous five years were included in the analysis.
      Qualitative information was further obtained from traditional birth attendants
      (TBAs), mothers-in-law, community leaders and pregnant women. High-risk practices
      were common and related to local custom and lack of knowledge on the importance
      of cleanliness. Husband's level of education greater than fifth grade
      significantly reduced the high-risk practices in all stages of childbirth,
      independent of other socio-economic, biological and village variables.

PMID- 11310815
TI  - Long-term management of chronic depression.
AB  - Untreated major depression tends to either wax and wane, with repeated acute
      episodes, or persist in a chronic unremitting state, which occurs in up to 35% of
      depressed patients. After acute remission, those with treated chronic major
      depression are at high risk of depressive relapse and recurrence. Strategies to
      reduce the risk of relapse and recurrence include achieving full acute remission,
      continuing antidepressant treatment with optimal patient adherence, and adding
      modified cognitive-behavioral psychotherapy. This article will review data
      relevant to the long-term management of chronic major depression.

PMID- 11310814
TI  - Acute and maintenance treatment of chronic depression.
AB  - Chronic forms of depression account for approximately one third of all
      depressions. They are underrecognized and undertreated. This article defines the
      types of chronic depressions (dysthymic disorder, double depression, chronic
      major depression, and major depression in incomplete remission). A review of
      treatments for patients with these conditions is provided. The basic principles
      of treatment of chronic depression involve longer treatment and higher doses than
      are usually required for acute major depression. The impact of psychosocial
      disability and severity of depressive symptoms can be ameliorated with
      appropriate treatment. Newer treatments, such as the combination of psychotherapy
      and pharmacotherapy, may prove to be of greatest benefit for individuals with
      chronic mood disorders.

PMID- 11310816
TI  - Algorithm for the treatment of chronic depression.
AB  - Chronic depression, which is marked by a course of illness lasting 2 years or
      more, encompasses 4 subtypes of depressive illness: (1) chronic major depressive
      disorder, (2) dysthymic disorder, (3) dysthymic disorder with major depressive
      disorder ("double depression"), and (4) major depressive disorder with poor
      interepisodic recovery (i.e., in incomplete remission). In the 1990s, chronic
      depression had a reported prevalence rate of 3% to 5% and accounted for 30% to
      35% of all cases of depression in the United States. The authors present an
      algorithm modified from the Texas Medication Algorithm Project for patients with
      chronic depression. This treatment algorithm recommends a progression of steps or
      stages in treating chronic depression. The first stage is monotherapy with the
      selective serotonin reuptake inhibitors, nefazodone, bupropion sustained release,
      venlafaxine extended release, mirtazapine, or psychotherapy. Later options
      include combination therapy, electroconvulsive therapy, atypical antipsychotics,
      and novel treatments. Utilization of a comprehensive treatment algorithm for
      chronic major depression should encourage efficient, efficacious treatment.

PMID- 11310817
TI  - A consumer perspective of diagnosis and treatment of chronic major depression.
AB  - The National Depressive and Manic-Depressive Association (National DMDA) is a
      nonprofit, mission-driven, consumer advocacy organization that was founded to
      educate patients, their families, and the public about the nature and management
      of depressive and manic depressive illness. Although treatments for mood
      disorders have been available for decades, individuals with chronic major
      depression are often misdiagnosed or inappropriately treated. Serious gaps in the
      translation of research findings into clinical management exist and are
      attributable to patient, provider, and health care system factors. This article
      discusses the barriers to diagnosis and the ways to improve recognition and
      treatment of chronic major depression from the consumer perspective.

PMID- 11310818
TI  - The societal costs of chronic major depression.
AB  - Major depression is a widespread, often chronic disorder affecting the
      individual, his or her family, and society as a whole. It incurs tremendous
      social and financial costs in the form of impaired relationships, lost
      productivity, and lost wages. Although chronic major depression is eminently
      treatable, it continues to be undertreated and underrecognized. This is
      particularly true in primary care settings, where physicians are usually the
      first to encounter chronic depression but are seldom trained to distinguish
      depression from other medical illnesses with similar symptoms. In addition,
      because of the stigma attached to depression, patients often characterize their
      symptoms as part of a physical illness or fail to report them to a clinician at
      all. This article discusses the epidemiology of depression, its impact and burden
      on society, and its special character (including diagnosis and treatment) as a
      chronic illness.

PMID- 11310819
TI  - Hepatitis C virus transmission in a pediatric oncology ward: analysis of an
      outbreak and review of the literature.
AB  - Hospital-related hepatitis C virus (HCV) infections continue to occur even after
      the introduction of blood donor screening. We report an outbreak of HCV in nine
      patients of a pediatric oncology ward in 1996/1997. Sequencing of the
      hypervariable genomic region 1 (HVR1) of the E2/NS1 region showed near identity
      between HCV isolates from these patients as evidence for infection with the same
      virus. Despite a detailed and careful investigation, the source of infection and
      the mode of virus transmission could not be established. Based on a review of the
      current literature about nosocomial HCV infection and HCV infection in children,
      hypotheses for possible means of transmission in this outbreak are discussed.

PMID- 11310820
TI  - Multiple sclerosis: current pathophysiological concepts.
AB  - Multiple sclerosis (MS) is an often disabling disease primarily affecting young
      adults that exhibits extraordinary clinical, radiological, and pathological
      heterogeneity. We review the following: (a) known environmental and genetic
      factors that contribute to MS susceptibility; (b) current knowledge regarding
      fundamental pathophysiological processes in MS, including immune cell recruitment
      and entry into the central nervous system (CNS), formation of the plaque, and
      orchestration of the immune response; (c) descriptive and qualitative distinct
      pathological patterns in MS and their implications; (d) the evidence supporting
      the causative role of direct toxins, cell-mediated and humorally mediated immune
      mechanisms, and the concept of a "primary oligodendrogliopathy" in demyelination
      and axonal injury; (e) the potential benefits of inflammation; (f) the prospects
      for remyelination; and (g) therapeutic implications and approaches suggested by
      putative pathophysiological mechanisms.

PMID- 11310821
TI  - Fas gene mutations in prostatic intraepithelial neoplasia and concurrent
      carcinoma: analysis of laser capture microdissected specimens.
AB  - Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling
      through binding of Fas ligand. Mutations of the Fas gene might be involved in
      proliferative diseases of the prostate by prolongation of programmed cell death
      of prostatic epithelial cells. Using the laser capture microdissection method,
      Fas gene mutations were examined on genomic DNA extracted from lesions with high
      grade prostatic intraepithelial neoplasia (HGPIN), a possible precursor of
      prostatic cancer (PCA), and from PCA. A total of 193 lesions, 111 with HGPIN, 55
      with PCA, and 27 benign glands, were microdissected from 27 patients with PCA.
      Polymerase chain reaction-amplified products were directly sequenced. Loss of
      heterozygosity (LOH) was examined at four sites of known polymorphisms. Fas gene
      mutations were detected in HGPIN: 4 of 27 (14.8%) cases or 4 of 111 (3.6%)
      lesions. All were point mutations: three missense and one nonsense in the death
      domain. Benign proliferative glands adjoining HGPIN and/or PCA, and PCA never
      showed mutations. LOH was found in 31.3% of PCA and 25% of HGPIN lesions, but was
      never found in benign glands. Exclusive occurrence of Fas mutations in HGPIN
      might underlie the development of these lesions. Occasional findings of LOH in
      HGPIN and PCA suggested that genetic instability might occur during the early
      phase of prostatic carcinogenesis.

PMID- 11310822
TI  - Molecular single-cell analysis of Hodgkin- and Reed-Sternberg cells harboring
      unmutated immunoglobulin variable region genes.
AB  - Hodgkin- and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease of the B
      lineage are the clonal progeny of antigen-experienced B cells harboring highly
      mutated immunoglobulin variable (V) region genes. Based on the detection of
      obviously destructive somatic mutations in a fraction of cases, we speculated
      that H/RS cells may be derived from a pre-apoptotic germinal center B cell.
      Seemingly contradicting this speculation, we present here the first case of
      classical Hodgkin's disease with H/RS cells harboring unmutated, potentially
      functional V region genes, which may indicate the derivation of the H/RS clone
      from a naive B cell. However, germinal center founder cells, which have not yet
      acquired somatic mutations, already have the intrinsic propensity to die by
      apoptosis. Thus, the rare occurrence of H/RS cells with unmutated V genes is
      expected if the H/RS cells are derived from the pool of pre-apoptotic germinal
      center B cells.

PMID- 11310823
TI  - Ulcerative proctitis, rectal prolapse, and intestinal pseudo-obstruction in
      transgenic mice overexpressing hepatocyte growth factor/scatter factor.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) can stimulate growth of
      gastrointestinal epithelial cells in vitro; however, the physiological role of
      HGF/SF in the digestive tract is poorly understood. To elucidate this in vivo
      function, mice were analyzed in which an HGF/SF transgene was overexpressed
      throughout the digestive tract. Nearly a third of all HGF/SF transgenic mice in
      this study (28 of 87) died by 6 months of age as a result of sporadic intestinal
      obstruction of unknown etiology. Enteric ganglia were not overtly affected,
      indicating that the pathogenesis of this intestinal lesion was different from
      that operating in Hirschsprung's disease. Transgenic mice also exhibited a rectal
      inflammatory bowel disease (IBD) with a high incidence of anorectal prolapse.
      Expression of interleukin-2 was decreased in the transgenic colon, indicating
      that HGF/SF may influence regulation of the local intestinal immune system within
      the colon. These results suggest that HGF/SF plays an important role in the
      development of gastrointestinal paresis and chronic intestinal inflammation.
      HGF/SF transgenic mice may represent a useful model for the study of molecular
      mechanisms associated with a subset of IBD and intestinal pseudo-obstruction.
      Moreover, our data identify previously unappreciated side effects that may be
      encountered when using HGF/SF as a therapeutic agent.

PMID- 11310824
TI  - Redefining the significance of aneuploidy in the prognostic assessment of
      colorectal cancer.
AB  - The aberrant content of DNA, or aneuploidy, is a hallmark of tumor cells and may
      be associated with malignant potential. Based on the hypothesis that aneuploidy,
      as a form of genetic instability, results in an increased capability to generate
      cell heterogeneity, we investigated whether a comprehensive assessment of
      aneuploidy extent and degree might be a reliable indicator of tumor
      aggressiveness. DNA content was determined by flow cytometry in the infiltrating
      front of 131 paraffin-embedded primary colorectal carcinomas collected in a
      prospective design. Enrichment of tumor cells by sample microdissection resulted
      in neoplastic cell contents above 75%. An estimate of aneuploidy, the aneuploidy
      index (AI), was calculated as the tumor DNA content adjusted by the percentage of
      diploid and aneuploid cells in G0/G1. Thirty-nine tumors were diploid, 90
      hyperdiploid, and 2 hypodiploid. The mean AI in aneuploid tumors was 1.20+/-0.17
      and correlated with Dukes' stage and metastasis (p < 0.05). A high AI (receiver
      operating characteristic curve cutoff value greater than 1.14) predicted a poorer
      outcome in univariate (p = 0.004) and multivariate (p = 0.01) analyses. Based on
      these results, we postulate that aneuploidy is the molecular engine of
      progression in a subset of colorectal cancers, in which the AI seems to be a
      sensible and independent gauge of malignant potential. The AI determination may
      have prognostic application in colorectal cancer, especially in low-grade tumors,
      which might benefit from coadjuvant therapies.

PMID- 11310825
TI  - Differential and mutually exclusive expression of CD95 and CD95 ligand in
      epithelia of normal pancreas and chronic pancreatitis.
AB  - Acinar regression in chronic pancreatitis may be due to immune attack in
      parenchymal areas neoexpressing HLA-DR molecules. CD4+Th1 cytotoxic T cells
      induce apoptosis of their targets via oligomerizing CD95 (APO-1/Fas) death
      receptors on target cells by their CD95 ligand (CD95L). We determined the
      expression of CD95 and CD95L in epithelia of normal and chronically inflamed
      pancreatic tissues. We applied RT-PCR and Western blotting for CD95L expression
      profiles, serial frozen section immunohistochemistry to detect CD95, CD95L, and
      HLA-DR molecules, CD3, CD4, CD11c, and S-100 protein (S100p). Normal pancreases
      and chronic pancreatitis contain CD95L message and protein. Immunohistochemistry
      revealed a mutually exclusive expression of CD95 and CD95L. Physiologically,
      acini were CD95-/CD95L+, ducts were CD95-/CD95L-, and islets were CD95-/CD95L+.
      In areas of lymphohistiocytic infiltration, mainly consisting of CD3+CD4+ T cells
      and CD11c+, CD4+/-, S100p+ interstitial dendritic cells, and in areas of initial
      fibrosis, acini and ducts were HLA-DR+, acini CD95+/CD95L-, and ducts CD95+/CD95L
      . Islet cells were CD95-/CD95L+ in both conditions. IFNgamma levels in protein
      lysates, as measured by an immunoassay, were significantly higher in chronic
      pancreatitis than in normal pancreas (p < 0.0003). In vitro, IFNgamma down
      modulated CD95L message and protein in ASPC1 and BxPc3 pancreatic carcinoma
      cells. In conclusion, pancreatic epithelia differentially express CD95 and CD95L
      in a mutually exclusive manner. In chronic pancreatitis the CD95-/CD95L+ status
      is conserved in islet cells even in the vicinity of lymphohistiocytic
      infiltrates, whereas it is lost in acini coexpressing HLA-DR. As a potential
      consequence, and possibly triggered by local release of IFNgamma, CD4-Th1 cells
      may cognately interact with and successfully attack exocrine cells by triggering
      CD95 on their target without being killed by epithelial, CD95L-mediated,
      counterattack.

PMID- 11310826
TI  - Interleukin-11 up-regulates survivin expression in endothelial cells through a
      signal transducer and activator of transcription-3 pathway.
AB  - Interleukin-11 (IL-11) reduces injury both in vivo and in vitro, but the
      mechanisms are unknown. Stimulation of serum- and growth factor-deprived HUVEC
      with IL-11 increased survivin mRNA and protein expression levels in a dose
      dependent manner, with maximal induction at 50 to 100 ng/ml of IL-11. Survivin
      mRNA expression peaked after 3 to 6 hours of IL-11 treatment and decreased by 24
      hours. Survivin protein expression was maximal at 6 hours of treatment and
      remained elevated through 24 hours. Survivin induction may be mediated by
      activation of protein kinase B/Akt, but IL-11 failed to activate this pathway in
      HUVEC. IL-11 did activate signal transducer and activator of transcription (STAT)
      3 and IL-11 failed to induce survivin expression in HUVEC transduced with a
      dominant-negative STAT3 mutant, whereas control-transduced HUVEC responded
      normally. An IL-11 transgene caused increased survivin mRNA expression in mice
      compared with control littermates. Intradermal injection of IL-11 (500 ng) into
      human skin xenografts on immunodeficient mice up-regulated survivin protein in
      microvascular endothelium and epithelial keratinocytes. We conclude that IL-11
      induces expression of survivin, an antiapoptotic protein, in vitro and in vivo,
      and identify STAT3 as a critical mediator of this response.

PMID- 11310827
TI  - Potential role of the chemokine receptors CXCR3, CCR4, and the integrin
      alphaEbeta7 in the pathogenesis of psoriasis vulgaris.
AB  - Various adhesion molecules have been implicated in T lymphocyte binding to dermal
      vascular endothelium in psoriasis vulgaris, but the chemotactic signals that
      promote subsequent homing into the adjacent dermis and overlying epidermis are
      poorly defined. We studied chemokine receptor (CCR1-CCR5, CXCR1-CXCR3), chemokine
      (interferon-gamma inducible protein 10 [IP-10]), monokine induced by interferon
      gamma (MIG), thymus and activation-regulated chemokine (TARC), macrophage-derived
      chemokine (MDC), and adhesion molecule (cutaneous lymphocyte antigen [CLA], E
      selectin, lymphocyte function-associated antigen-1 [LFA-1], intercellular
      adhesion molecule-1 [ICAM-1], very late antigen 4 [VLA-4], vascular cell adhesion
      molecule-1 [VCAM-1], alphaEbeta7, and E-cadherin) expression in psoriasis by
      immunohistology, flow cytometry, and molecular techniques. CXCR3 and CCR4 were
      expressed by dermal CD3+ lymphocytes, and their chemokine ligands, IP-10, MIG,
      TARC, and MDC, were up-regulated in psoriatic lesions. Keratinocytes stimulated
      with tumor necrosis factor-alpha and interferon-gamma up-regulated expression of
      IP-10, MIG, and MDC mRNA, whereas dermal endothelial cells, similarly stimulated,
      up-regulated expression of IP-10, MDC, and TARC mRNA, suggesting that these cell
      types were sources of the chemokines detected in biopsies. There was enhanced
      expression of E-selectin, CLA, LFA-1, ICAM-1, VLA-4, VCAM-1, and alphaEbeta7 in
      psoriatic lesions versus nonlesional skin. Finally, intra-epidermal CLA+ and
      alphaEbeta7+ T lymphocytes selectively expressed the chemokine receptor CXCR3.
      Collectively, these data suggest that CXCR3 and CCR4 may be involved in T
      lymphocyte trafficking to the psoriatic dermis and that CXCR3 is selectively
      involved in subsequent T cell homing to the overlying epidermis.

PMID- 11310828
TI  - Nuclear factor-kappaB regulates cyclooxygenase-2 expression and cell
      proliferation in human gastric cancer cells.
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcriptional regulator of inducible
      expression of genes including cyclooxygenase-2 (COX-2), regulating cell
      proliferation. NF-kappaB is kept silent in the cytoplasm via interaction with the
      inhibitory protein IkappaBalpha and transmigrated into the nucleus upon
      activation. However, constitutive NF-kappaB has been found in the nucleus of some
      cancer cells. We investigated the role of NF-kappaB in COX-2 expression and cell
      proliferation in human gastric cancer AGS cells. AGS cells were treated with
      antisense oligodeoxynucleotide (AS ODN) or sense oligodeoxynucleotide (S ODN) for
      the NF-kappaB subunit p50, or they were transfected with a mutated IkappaBalpha
      gene (MAD-3 mutant) or a control vector, pcDNA-3. AGS cells were treated with COX
      2 inhibitors such as indomethacine and NS-398 or prostaglandin E2. mRNA
      expression for COX-2, and protein levels for p50, IkappaBalpha, and COX-2 were
      determined by reverse transcription polymerase chain reaction and Western blot
      analysis. The NF-kappaB levels were examined by electrophoretic mobility shift
      assay. Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha)
      levels were determined by enzyme-linked immunosorbent assay. Cell proliferation
      was assessed by viable cell counting, [3H] thymidine incorporation, and colony
      formation. The nuclear level of p50 decreased in AGS cells treated with AS ODN.
      The IkappaBa mutant was observed in cells transfected with the mutated IkappaBa
      gene. NF-kappaB was inhibited in cells treated with AS ODN or transfected with
      the mutated IkappaBalpha gene, compared with the cells treated with S ODN or
      transfected with control vector. Cell proliferation, mRNA expression and protein
      level of COX-2, and production of TXB2 and 6-keto-PGF1alpha were inhibited in
      cells treated with AS ODN or transfected with the mutated IkappaBalpha gene,
      which had lower NF-kappaB levels than cells treated with S ODN or transfected
      with control vector. COX-2 inhibitors suppressed cell proliferation and
      production of TXB2 and 6-keto-PGF1alpha, in a dose-dependant manner.
      Prostaglandin E2 prevented the inhibition of proliferation in cells treated with
      AS ODN or transfected with the mutated IkappaBalpha gene. In conclusion, NF
      kappaB mediates COX-2 expression, which may be related to cell proliferation, in
      human gastric cancer cells.

PMID- 11310829
TI  - Expressional regulation of angiopoietin-1 and -2 and the tie-1 and -2 receptor
      tyrosine kinases during cutaneous wound healing: a comparative study of normal
      and impaired repair.
AB  - It has become evident that a closely regulated presence of vascular endothelial
      growth factor (VEGF) and angiopoietin (Ang) factors determines the fate of blood
      vessel formation during angiogenesis. As angiogenesis is central to a normal
      wound-healing process, we investigated the regulation of Ang-1 and -2 and the
      related tyrosine kinase with immunoglobulin and epidermal growth factor homology
      (Tie)-1 and -2 receptors during normal repair in Balb/c mice and diabetes
      impaired wound healing conditions in genetically diabetic (db/db) mice. For both
      normal and impaired healing conditions, we observed a constitutive expression of
      Ang-1, which was paralleled by an increase of Ang-2 upon injury. Whereas the
      observed Ang-2 expression declines from Day 7 after injury in control mice,
      diabetic-impaired healing was characterized by still increasing amounts of Ang-2
      at these time points. Furthermore, Tie-1 was strongly induced during repair with
      a prolonged expression in diabetic mice, whereas Tie-2 expression was
      constitutive during normal repair but completely absent in diabetes-impaired
      healing. The overexpression of Ang-2 in the presence of markedly reduced VEGF in
      wounds of diabetic mice was associated with a dramatic decrease in endothelial
      cell numbers compared with normal healing as assessed by analysis of the
      endothelium-specific markers CD31 and von Willebrand factor, whereas the
      lymphatic endothelium remained stable as determined by expression of VEGF
      receptor-3 (VEGFR-3/Flt-4).

PMID- 11310830
TI  - Helicobacter pylori lipopolysaccharide hinders polymorphonuclear leucocyte
      apoptosis.
AB  - A prominent histologic feature of Helicobacter pylori infection is a dense
      infiltration of polymorphonuclear leukocytes (PMNL) in gastric mucosa. H. pylori
      lipopolysaccharide (LPS) has been recognized as a primary virulence factor
      evoking acute mucosal inflammatory reaction. Previous works have shown that H.
      pylori LPS immunologic activities are lower than those of enterobacterial LPS.
      However, the effect of H. pylori LPS on spontaneous PMNL apoptosis, and
      mechanisms by which this H. pylori LPS may promote PMNL survival remain to be
      established. In this study, we investigated, by both morphologic and biochemical
      approaches, the action of H. pylori LPS on PMNL apoptosis in vitro, using broth
      culture filtrates (BCF) of H. pylori strains with different genotypes. We found
      that BCF from H. pylori caused a significant delay in spontaneous PMNL apoptosis
      and this delay was independent of the VacA, cag pathogenicity island and urease
      status. We demonstrated that LPS in BCF is responsible for this effect because it
      was abrogated by the LPS antagonist B287 (a synthetic analog of
      Rhodobactersphaeroides lipid A). Moreover, BCF from H. pylori induced P42/44MAP
      kinase activation in PMNL. Similar results were obtained with BCF of an
      Escherichia coli strain. Taken together these data suggest that longer survival
      of PMNL induced by H. pylori LPS may increase gastric epithelium injury in H.
      pylori-associated diseases.

PMID- 11310831
TI  - Amyloid and nonfibrillar deposits in mice transgenic for wild-type human
      transthyretin: a possible model for senile systemic amyloidosis.
AB  - The human serum protein transthyretin (TTR) is highly fibrillogenic in vitro and
      is the fibril precursor in both autosomal dominant (familial amyloidotic
      polyneuropathy [FAP] and familial amyloidotic cardiomyopathy [FAC]) and sporadic
      (senile systemic amyloidosis [SSA]) forms of human cardiac amyloidosis. We have
      produced mouse strains transgenic for either wild-type or mutant (TTRLeu55Pro)
      human TTR genes. Eighty-four percent of C57BI/6xDBA/2 mice older than 18 months,
      transgenic for the wild-type human TTR gene, develop TTR deposits that occur
      primarily in heart and kidney. In most of the animals, the deposits are
      nonfibrillar and non-Congophilic, but 20% of animals older than 18 months that
      bear the transgene have human TTR cardiac amyloid deposits identical to the
      lesions seen in SSA. Amino terminal amino acid sequence analysis and mass
      spectrometry of the major component extracted from amyloid and nonamyloid
      deposits revealed that both were intact human TTR monomers with no evidence of
      proteolysis or codeposition of murine TTR. This is the first instance in which
      the proteins from amyloid and nonfibrillar deposits in the same or syngeneic
      animals have been shown to be identical by sequence analysis. It is also the
      first time in any form of amyloidosis that nonfibrillar deposits have been shown
      to systematically occur temporally before the appearance of fibrils derived from
      the same precursor in the same tissues. These findings suggest, but do not prove,
      that the nonamyloid deposits represent a precursor of the fibril. The differences
      in the ultrastructure and binding properties of the deposits, despite the
      identical sizes and amino terminal amino acid sequences of the TTR and the
      dissociation of deposition and fibril formation, provide evidence that in vivo
      factors, perhaps associated with aging, impact on both systemic precursor
      deposition and amyloid fibril formation.

PMID- 11310832
TI  - Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression
      precedes metaplastic differentiation of gastric epithelium.
AB  - The trefoil peptides spasmolytic polypeptide (SP), intestinal trefoil factor
      (ITF), and pS2 show lineage-specific expression in the normal gut and are
      strongly induced after mucosal injury. We assessed the relationship between this
      induction and the development of the regenerative epithelial lineage over time in
      the rat stomach and verified these observations in the metaplastic and dysplastic
      human stomach. Antral or colonic ulcers were induced in Wistar rats by
      application of serosal acetic acid and tissues harvested 2 hours to 125 days
      later. Human endoscopic biopsies or gastric resection specimens were also
      assessed. Tissues were examined by radioimmunoassay, immunoblotting, or
      immunohistochemistry for ITF, SP, and transforming growth factor alpha (rat) or
      ITF and pS2 (human) expression. ITF and SP mRNA in antral ulcer margins was
      localized by in situ hybridization. ITF and SP peptide expression rose steadily
      in ulcer margins after 4 days, with the rise in ITF being more pronounced. By 40
      days, several hundred-fold elevations in ITF levels were present, with a field
      effect in uninvolved mucosa. Hyperproliferative, elongated glands of
      undifferentiated cells expressing abundant trefoil peptides and acid sulfomucins
      were present after day 12 and persisted after ulcer healing. ITF mRNA was
      aberrantly expressed in basal and mid-regions of these regenerative glands. In
      contrast, transforming growth factor alpha peptide expression rose promptly after
      injury then fell to baseline levels with healing. Seven months after injury,
      gastric atrophy, intestinal metaplasia, and severe dysplasia with conserved ITF
      expression were seen. ITF was also induced in human intestinal metaplasia and
      conserved in all gastric cancers, whereas expression of the gastric peptide pS2
      was progressively reduced in the progression from metaplasia to dysplasia.
      Persistent, selective overexpression of ITF, possibly acting in an autocrine
      fashion, is a feature of regeneration after antral ulceration, and may provide
      insight into the nature of metaplastic phenotypes arising from chronic gastric
      injury. The loss of pS2 expression in metaplasia and cancer supports a role for
      this protein in gastric tumor suppression.

PMID- 11310833
TI  - CXCR3 chemokine receptor distribution in normal and inflamed tissues: expression
      on activated lymphocytes, endothelial cells, and dendritic cells.
AB  - Using new human CXCR3 chemokine receptor-specific monoclonal antibodies, we
      studied human CXCR3 tissue distribution in lymphoid and nonlymphoid organs, as
      well as in inflammatory conditions, including rheumatoid arthritis, Hashimoto's
      thyroiditis, and dermal vasculitis. CXCR3 was expressed by certain dendritic cell
      subsets, specifically myeloid-derived CD11c positive cells, not only in those
      present in normal lymphoid organs, but also in germinal centers generated in
      inflammatory conditions. CXCR3 expression was also detected in some lymphocyte
      subsets such as intraepithelial lymphocytes of secondary lymphoid organs and
      infiltrating lymphocytes in inflammatory conditions. In addition, CXCR3 was
      constitutively expressed by endothelial cells (EC) of vessels of medium and large
      caliber but not in small vessels from different organs. Finally, enhanced CXCR3
      expression was found in EC and in infiltrating lymphocytes with an activated
      phenotype in inflammatory diseases. The CXCR3 chemokine receptor may play a role
      in the regulation of leukocyte migration to inflammatory sites.

PMID- 11310834
TI  - Molecular characterization of a new ALK translocation involving moesin (MSN-ALK)
      in anaplastic large cell lymphoma.
AB  - The majority of anaplastic large cell lymphomas (ALCL) are associated with
      chromosomal abnormalities affecting the anaplastic lymphoma kinase (ALK) gene
      which result in the expression of hybrid ALK fusion proteins in the tumor cells.
      In most of these tumors, the hybrid gene comprises the 5' region of nucleophosmin
      (NPM) fused in frame to the 3' portion of ALK, resulting in the expression of the
      chimeric oncogenic tyrosine kinase NPM-ALK. However, other variant rearrangements
      have been described in which ALK fuses to a partner other than NPM. Here we have
      identified the moesin (MSN) gene at Xq11-12 as a new partner of ALK in a case of
      ALCL which exhibited a distinctive membrane-restricted pattern of ALK labeling.
      The hybrid MSN-ALK protein had a molecular weight of 125 kd and contained an
      active tyrosine kinase domain. The unique membrane staining pattern of ALK is
      presumed to reflect association of moesin with cell membrane proteins. In
      contrast to other translocations involving the ALK gene, the ALK breakpoint in
      this case occurred within the exonic sequence coding for the juxtamembrane
      portion of ALK. Identification of the genomic breakpoint confirmed the in-frame
      fusion of the whole MSN intron 10 to a 17 bp shorter juxtamembrane exon of ALK.
      The breakpoint in der(2) chromosome showed a deletion, including 30 bp of ALK and
      36 bp of MSN genes. These findings indicate that MSN may act as an alternative
      fusion partner for activation of ALK in ALCL and provide further evidence that
      oncogenic activation of ALK may occur at different intracellular locations.

PMID- 11310835
TI  - The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a
      target antigen of autoantibodies.
AB  - The bactericidal/permeability-increasing protein (BPI) is an endotoxin-binding
      neutrophil leukocyte-granule protein with antibacterial and anti-endotoxin
      properties. A recombinant form of BPI (rBPI21) has been developed and is being
      tested as a therapeutic agent to treat gram-negative bacterial infections and
      exposure to gram-negative bacterial endotoxin. BPI is also a target antigen of
      anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANCA are present in cystic
      fibrosis, inflammatory bowel disease, vasculitis, and primary sclerosing
      cholangitis; presence of BPI-ANCA appears associated with a higher inflammatory
      disease activity and greater organ damage. BPI-ANCA as well as ANCA directed at
      other neutrophil-granule proteins may exacerbate inflammation by nonspecific
      effects of extracellular and cell-associated immune complexes. BPI-ANCA may
      further worsen inflammation by reducing the ability of BPI to promote clearance
      of gram-negative bacteria and bacterial-associated endotoxin.

PMID- 11310836
TI  - Chemokines in cutaneous wound healing.
AB  - Healing of wounds is one of the most complex biological events after birth as a
      result of the interplay of different tissue structures and a large number of
      resident and infiltrating cell types. The latter are mainly constituted by
      leukocyte subsets (neutrophils, macrophages, mast cells, and lymphocytes), which
      sequentially infiltrate the wound site and serve as immunological effector cells
      but also as sources of inflammatory and growth-promoting cytokines. Recent data
      demonstrate that recruitment of leukocyte subtypes is tightly regulated by
      chemokines. Moreover, the presence of chemokine receptors on resident cells
      (e.g., keratinocytes, endothelial cells) indicates that chemokines also
      contribute to the regulation of epithelialization, tissue remodeling, and
      angiogenesis. Thus, chemokines are in an exclusive position to integrate
      inflammatory events and reparative processes and are important modulators of
      human-skin wound healing. This review will focus preferentially on the role of
      chemokines during skin wound healing and intends to provide an update on the
      multiple functions of individual chemokines during the phases of wound repair.

PMID- 11310837
TI  - The effects of extracellular pH on immune function.
AB  - The effect of alterations in extracellular pH on cellular and humoral immune
      function is reviewed. Because acidic pH predominates at inflammatory loci and
      other sites of immune activity, most studies to date focus on the effect of
      acidic rather than alkaline pH. Investigations on polymorphonuclear leukocytes
      demonstrate mainly inhibition of chemotaxis, respiratory activity, and
      bactericidal capacity at reduced pH. Evidence of impaired lymphocyte cytotoxicity
      and proliferation at acidic pH is also beginning to emerge. Many of the clinical
      acidoses are accompanied similarly by immunodeficiency. Studies on macrophages
      and eosinophils are few and inconclusive. A small number of studies demonstrate
      acid-induced activation of complement proteins and the alternative complement
      pathway, plus increased antibody-binding to leukocytes at lowered pH. A
      differential effect of acidic pH on humoral and cellular immunity may, therefore,
      exist. Increasing recognition of the significance of extracellular pH in relation
      to immune function warrants further studies in this presently incomplete but
      rewarding field.

PMID- 11310838
TI  - NK cell-mediated anti-tumor immune response to human prostate cancer cell, PC-3:
      immunogene therapy using a highly secretable form of interleukin-15 gene
      transfer.
AB  - Interleukin (IL)-15 is a pleiotropic cytokine that is important for innate and
      adaptive immune cell homeostasis. The expression of IL-15 protein is controlled
      by posttranscriptional mechanisms. Here, we constructed a human IL-15 expression
      vector consisting of the human IL-2 signal peptide, the human IL-15 mature
      peptide-coding sequences, and an out-of-frame human growth hormone gene. Human
      prostate cancer cells, PC-3, transfected with this highly secretable form of the
      IL-15 gene, successfully secreted abundant bioactive IL-15 protein. In nude mice,
      the growth of PC-3 cells producing IL-15 was remarkably retarded. NK cell
      depletion using anti-asialo GM1 antibody restored tumorigenicity. Histologically,
      tumors derived from IL-15-producing PC-3 cells contained necrotic areas with high
      apoptotic index. Splenocytes incubated with supernatant of transfectants killed
      target PC-3 cells and expressed a significantly high level of mIFN-gamma mRNA.
      These observations suggest that NK cell-mediated, anti-tumor effects of IL-15
      could provide a potential rationale for gene therapy of prostate cancer.

PMID- 11310839
TI  - Ovalbumin aerosols induce airway hyperreactivity in naive DO11.10 T cell receptor
      transgenic mice without pulmonary eosinophilia or OVA-specific antibody.
AB  - The pathobiology of allergic asthma is being studied using murine models, most of
      which use systemic priming followed by pulmonary challenges with the immunizing
      antigen. In general, mice develop eosinophilic pulmonary inflammation, increased
      antigen-specific immunoglobulins, and airway hyperreactivity (AHR), all of which
      are dependent on antigen-specific T cell activation. To establish a model of
      allergic asthma, which did not require systemic priming, we exposed DO11.10 T
      cell receptor transgenic mice, which have an expanded repertoire of ovalbumin
      (OVA), peptide-specific T cells, to limited aerosols of OVA protein. DO11.10 +/-
      mice developed AHR in the absence of increases in total serum IgE, OVA-specific
      IgG, or eosinophilia. The AHR was accompanied by pulmonary recruitment of antigen
      specific T cells with decreased expression of CD62L and CD45RB and increased
      expression of CD69, a phenotype indicative of T cell activation. Our results
      support recent hypotheses that T cells mediate AHR directly.

PMID- 11310840
TI  - UVB-irradiated dendritic cells are impaired in their APC function and tolerize
      primed Th1 cells but not naive CD4+ T cells.
AB  - We have shown that low-dose UVB radiation converts Langerhans cells (LC) from
      immunogenic to tolerogenic APC. Therefore, we questioned whether low-dose UVB
      irradiation of bone marrow-derived dendritic cells (DC) alters their APC
      function, thereby inducing tolerance in T cells. To address this issue,
      cocultures of DC; and naive, allogeneic T cells; naive, OVA-specific TCR
      transgenic T cells from DO11.10 mice; or primed, antigen-specific T cells using
      the Th1 clone AE7 were analyzed. First, we found low-dose UVB-irradiated DC (UVB
      DC) to dose-dependently (50-200 J/m2) inhibit T-cell proliferation of naive and
      primed T cells. In addition, supernatants harvested from cocultures of UVB-DC and
      naive T cells showed markedly reduced levels of IL-2 and IFN-gamma and to a
      lesser degree of IL-4 and IL-10, suggesting a preferential down-regulation of Th1
      responses by UVB-DC. FACS analysis of UVB-DC revealed no changes in surface
      expression of MHC, costimulatory, and adhesion molecules. To test tolerance
      induction, allo- or antigen-specific T cells isolated from cocultures with
      unirradiated DC and UVB-DC were restimulated with unirradiated DC or IL-2. It is
      interesting that UVB-DC induced antigen-specific tolerance in the Th1 clone AE7.
      In contrast, UVB-DC induced a partial inhibition of allogeneic T-cell
      proliferation but no tolerance with similar unresponsiveness to restimulation
      with IL-2 and unirradiated DC irrespective of their haplotype. Similar
      observations were made when naive, TCR-transgenic T cells from DO11.10 mice were
      used. In conclusion, UVB-DC are impaired in their APC function and tolerize the
      primed antigen-specific Th1 clone AE7 but not naive allo- or OVA-specific T
      cells.

PMID- 11310841
TI  - Expression and function of galectin-3, a beta-galactoside-binding protein in
      activated T lymphocytes.
AB  - A soluble beta-galactoside-binding lectin, galectin-3 has been shown to be
      involved in cell adhesion and activation of immune cells. Although galectin-3 is
      known to be expressed in various types of cells, it has not been shown whether
      galectin-3 is expressed in T lymphocytes. We present evidence here that galectin
      3 is expressed in activated murine T lymphocytes including CD4+ and CD8+ T cells
      but not in resting T cells. Galectin-3 expression was induced by anti-CD3 mAb or
      mitogen and enhanced by common gamma-chain signaling cytokines, IL-2, IL-4, and
      IL-7, in activated T lymphocytes, whereas the inflammatory cytokines including
      TNF-alpha and IFN-gamma did not. Galectin-3 expression and proliferation were
      down-regulated by withdrawal of IL-2 and gamma irradiation. Antisense but not
      sense phosphorothioated oligonucleotides for galectin-3 inhibited galectin-3
      expression and blocked proliferation of T cells significantly. This study
      suggests that up-regulation of galectin-3 plays an important role in
      proliferation of activated T lymphocytes.

PMID- 11310842
TI  - CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells
      regulates shear-resistant leukocyte rolling via L-selectin.
AB  - Sulfation is an essential component of the selectin ligands, potentially mediated
      by members of a new family of carbohydrate sulfotransferases. In this study, we
      assessed the contributions of CHST1, CHST2, CHST3, and CHST4 in producing
      functional L-selectin ligands. Human umbilical vein endothelial cells
      predominantly expressed CHST1 and CHST2 transcripts with low levels of CHST3
      mRNA, while cytokine activation up-regulated CHST2 expression and induced low
      level CHST4 expression. A human umbilical vein endothelial cell line, EA.hy926,
      displayed functional L-selectin ligands that correlated with CHST1 and CHST2
      expression in the absence of CHST4 expression. Increased CHST1 or CHST2
      expression by a cell line expressing low-level L-selectin ligand activity during
      in vitro flow chamber assays increased rolling leukocyte numbers, reduced rolling
      velocities, and enhanced leukocyte rolling under higher shear stresses. These
      results suggest that CHST1 and CHST2 contribute to the generation of optimal L
      selectin ligands in vascular endothelial cells at sites of inflammation.

PMID- 11310843
TI  - The collagenous domain of class A scavenger receptors is involved in macrophage
      adhesion to collagens.
AB  - Class A macrophage scavenger receptors (MSRs) have a remarkably broad ligand
      specificity and are well-known for their roles in atherogenesis and host defense.
      Recently, we demonstrated that these receptors also recognize and mediate
      adhesion to denatured forms of type I collagen. In this study, the involvement of
      the collagenous domain of MSRs in binding to denatured type I collagen was
      investigated. Transient expression of full-length, native type II MSR in COS-1
      cells conferred adhesion to denatured type I collagens, whereas expression of a
      truncated receptor lacking the distal portion of the collagenous domain did not.
      Further, a synthetic peptide derived from the collagenous domain was effective in
      abrogating Mphi adhesion to denatured forms of type I collagen. We also addressed
      collagen-type specificity by examining MSR affinity for type III and type IV
      collagens. As with type I collagen, Mphis adhered only to denatured forms of type
      III collagen. Moreover, the adhesion was mediated by MSRs. In contrast, adhesion
      to denatured type IV collagen was not shown to be MSR-dependent, but adhesion to
      the native form was. MSR-mediated adhesion to types III and IV collagens was also
      shown to be dependent on the collagenous domain. Taken together, these data
      strongly suggest that the collagenous domain is involved in MSR-mediated adhesion
      to denatured forms of types I and III collagens and native, but not denatured,
      type IV collagen.

PMID- 11310844
TI  - Genetic background of attenuated Salmonella typhimurium has profound influence on
      infection and cytokine patterns in human dendritic cells.
AB  - Salmonella typhimurium (ST) can cause infection in man, and attenuated strains
      are under consideration as live vaccine vectors. However, little is known about
      the interaction of ST with human dendritic cells (DC). Here, we compared the
      consequences of exposure of human, monocyte-derived DC with different attenuated
      strains of ST. Infection was observed with all four strains tested (wild type,
      PhoP-, PhoPc, and AroA), but the PhoPc strain was by far the most efficient.
      Intracellular persistence of wild type and PhoP- was longer than that of PhoPc
      and AroA, both of which were largely eliminated within 24 h. Most DC survived
      infection by the attenuated strains, although apoptosis was observed in a
      fraction of the exposed cells. All strains induced DC maturation, independent
      from the extent of infection. Although all strains stimulated secretion of TNF
      alpha and IL-12 strongly, PhoPc induced significantly less IL-10 than the other
      three strains and as much as 10 times less IL-10 than heat-killed PhoPc,
      suggesting that this mutant suppressed the secretion of IL-10 by the DC. These
      data indicate that infectivity, bacterial elimination, and cytokine secretion in
      human DC are controlled by the genetic background of ST.

PMID- 11310845
TI  - Induction of soluble antitumoral mediators by synthetic analogues of bacterial
      lipoprotein in bone marrow-derived macrophages from LPS-responder and 
      nonresponder mice.
AB  - Macrophage-dependent antitumoral activity is partly mediated by soluble factors
      including cytokines, reactive-oxygen intermediates (ROIs), and reactive-nitrogen
      intermediates (RNIs). Activation of macrophages for tumor cytotoxicity can be
      achieved with various bacterial compounds, such as lipopolysaccharides (LPSs),
      muramyl-dipeptides, and lipopeptides. We studied the production and release of
      oxygen radicals, nitric oxide, and tumor necrosis factor alpha (TNF-alpha) by
      bone marrow-derived macrophages (BMDMs) of different mouse inbred strains after
      they were stimulated with the lipopeptide P3CSK4, a water-soluble synthetic
      analogue of the lipidated N terminus of bacterial lipoprotein. The lipopeptide
      was able to induce a strong, long lasting release of oxygen radicals in BALB/c
      mouse macrophages. Furthermore, it induced nitric oxide release from BMDMs of
      several mouse strains (BALB/c, C57Bl/6, C57Bl/10ScSn, Sv129, NMRI, and LPS
      nonresponder C57Bl/10ScCr). Stimulation with P3CSK4 also resulted in comparable
      production of TNF-alpha in LPS-responder and nonresponder BMDMs from C57Bl/10ScSn
      mice and C57Bl/10ScCr mice, respectively. All three antitumoral mediators reached
      functional levels or concentrations as shown by the strong cytostatic/cytotoxic
      activity of lipopeptide-activated macrophages for the cell lines Abelson 8-1,
      M12.5/P815, and L929, which are sensitive to ROIs, nitric oxide, and TNF-alpha,
      respectively. We found that synthetic lipopeptides can induce the secretion of
      effective levels of soluble tumor-cytotoxic/cytostatic mediators in BMDMs of LPS
      responsive and, of particular interest, also of LPS-unresponsive mice. This
      result could indicate that the highly effective bacterial-macrophage activators
      P3CSK4 and LPS use different receptors and/or different intracellular signal
      transduction pathways.

PMID- 11310846
TI  - Requirement for STAT1 in LPS-induced gene expression in macrophages.
AB  - This study examines the role of the signal transducer and activator of
      transcription 1 (STAT1) in induction of lipopolysaccharide (LPS)-stimulated gene
      expression both in vitro and in vivo. LPS-induced expression of an interferon
      (IFN)-inducible 10-kDa protein (IP-10), IFN regulatory factor-1 (IRF-1), and
      inducible nitric oxide synthase (iNOS) mRNAs was severely impaired in macrophages
      prepared from Stat1-/- mice, whereas levels of tumor necrosis factor alpha and KC
      (a C-X-C chemokine) mRNA in LPS-treated cell cultures were unaffected. A similar
      deficiency in LPS-induced gene expression was observed in livers and spleens from
      Stat1-/- mice. The reduced LPS-stimulated gene expression seen in Stat1-/-
      macrophages was not the result of reduced activation of nuclear factor kappaB.
      LPS stimulated the delayed activation of both IFN-stimulated response element and
      IFN-gamma-activated sequence binding activity in macrophages from wild-type mice.
      Activation of these STAT1-containing transcription factors was mediated by the
      intermediate induction of type I IFNs, since the LPS-induced IP-10, IRF-1, and
      iNOS mRNA expression was markedly reduced in macrophages from IFN-alpha/betaR-/-
      mice and blocked by cotreatment with antibodies against type I IFN. These results
      indicate that indirect activation of STAT1 by LPS-induced type I IFN participates
      in promoting optimal expression of LPS-inducible genes, and they suggest that
      STAT1 may play a critical role in innate immunity against gram-negative bacterial
      infection.

PMID- 11310847
TI  - CD38 expression and functional activities are up-regulated by IFN-gamma on human
      monocytes and monocytic cell lines.
AB  - Human CD38, a surface molecule expressed by immature and activated T and B
      lymphocytes, has been characterized as a molecule transducing activation and
      proliferation signals, and intervening in adhesion to endothelium via its ligand
      CD31. CD38 is also a complex ectoenzyme featuring ADP-ribosyl cyclase/cyclic ADP
      ribose hydrolase activities, leading to the synthesis and degradation of cADPR, a
      Ca+-mobilizing agent. We investigated the effects of monocyte-activating stimuli
      (IFN-gamma, IL-2, LPS, TNF-alpha, and GM-CSF) on the expression and function of
      CD38, starting from the observation that human monocytes and the derived lines
      U937, THP-1, and Mono-Mac-6 bear the molecule on their surface. Our results
      indicate that IFN-gamma is a strong up-modulator of CD38, and IL-2 increases its
      expression only modestly. LPS, TNF-alpha, and GM-CSF had no detectable effects.
      Treatment with IFN-gamma produced a dose- and time-dependent up-regulation of
      CD38 in monocytes and monocytic lines, which was paralleled by increased ADP
      ribosyl cyclase/cyclic ADP-ribose hydrolase activities. Furthermore, CD38
      ligation by specific MoAb reduced the IFN-gamma-dependent enhancement of monocyte
      dynamic adhesion to endothelial monolayers. These findings identify IFN-gamma as
      a modulator of monocytic CD38 expression and indicate that CD38 plays a specific
      role in the activation and adhesion processes performed by monocytes.

PMID- 11310848
TI  - Transforming growth factor-beta suppresses tumor necrosis factor alpha-induced
      matrix metalloproteinase-9 expression in monocytes.
AB  - The inflammatory response is marked by the release of several cytokines with
      multiple roles in regulating leukocyte activities, including the secretion of
      matrix metalloproteinases (MMPs). Although the effects of individual cytokines on
      monocyte MMP expression have been studied extensively, few studies have examined
      the influence of combinations of cytokines, which are likely present at
      inflammatory sites. Herein, we report our investigation of the combinatorial
      effects of tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)
      beta on MMP-9 synthesis. We found that TGF-beta suppressed TNF-alpha-induced MMP
      9 secretion by MonoMac-6 monocytic cells in a dose-dependent manner, with a
      maximal effect of TGF-beta observed at 1 ng/ml. Such suppression was likely
      regulated at the pretranslational level, because steady-state mRNA levels of TNF
      alpha-induced MMP-9 were reduced by TGF-beta, and pulse-chase radiolabeling also
      showed a decrease in new MMP-9 protein synthesis. The suppressive effects of TGF
      beta were time dependent, because short exposures to TNF-alpha before TGF-beta or
      simultaneous exposure to both cytokines efficiently reduced MMP-9 secretion.
      Expression of the tissue inhibitor of metalloproteinases (TIMP)-1 and TNF-alpha
      receptors was unaffected by either cytokine individually or in combination.
      Affinity binding with radiolabeled TGF-beta demonstrated that levels of TGF-beta
      receptors were not increased after preincubation with TGF-beta. Suppression of
      TNFalpha-induced MMP-9 secretion by TGF-beta correlated with a reduction in
      prostaglandin E2 (PGE2) secretion. Furthermore, the effect of TGF-beta or
      indomethacin on blockage of TNF-alpha-stimulated MMP-9 production was reversed by
      the addition of either exogenous PGE2 or the cyclic AMP (cAMP) analogue Bt2cAMP.
      Thus, we concluded that TGF-beta acts as a potent suppressor of TNF-alpha-induced
      monocyte MMP-9 synthesis via a PGE2- and cAMP-dependent mechanism. These results
      suggest that various combinations of cytokines that are present at inflammatory
      sites, as well as their balance during different stages of inflammation, may
      provide the signals necessary for directing MMP-mediated leukocyte activities.

PMID- 11310849
TI  - Adenoviral gene delivery can inactivate Kupffer cells: role of oxidants in NF
      kappaB activation and cytokine production.
AB  - Kupffer cells play a significant role in the pathogenesis of several liver
      diseases; therefore, a potential therapeutic strategy would be to inactivate the
      Kupffer cell with a gene-delivery system. Although recombinant adenovirus
      provides robust, transgene expression in parenchymal cells, whether adenovirus
      transduces Kupffer cells is unclear. Thus, the purpose of this study was to
      evaluate this possibility. In animals infected with adenovirus, Kupffer cells
      were identified positively to express adenoviral transgenes by
      immunohistochemical techniques and Western blot analysis, indicating that Kupffer
      cells are transduced in vivo. Indeed, isolated Kupffer cells were transduced in
      vitro with recombinant adenovirus in a dose-dependent manner. Moreover,
      adenoviral transduction of Kupffer cells was blocked by inhibitors of alphaVbeta5
      integrin, the co-receptor for adenovirus binding, supporting the hypothesis that
      adenovirus transduces Kupffer cells via an alphaVbeta5 integrin-dependent
      mechanism. Indeed, it is shown here that Kupffer cells express alphaVbeta5
      integrins. In a functional assay, infection of isolated Kupffer cells with
      adenovirus containing superoxide dismutase or IkappaB alpha super-repressor
      blunted LPS-induced nuclear transcription factor kappa B (NF-kappaB) activation
      and tumor necrosis factor alpha (TNF-alpha) production but not IL-10 production.
      Moreover, superoxide production was blocked by expression of superoxide
      dismutase. These data support the hypothesis that LPS-induced NF-kappaB
      activation and TNF-alpha production in Kupffer cells are oxidant-dependent. These
      findings suggest that Kupffer cell-targeted approaches may be a potential
      therapeutic strategy against many inflammatory diseases including early alcohol
      induced liver injury.

PMID- 11310850
TI  - Differential effects of 15-deoxy-delta(12,14)-prostaglandin J2 and a peroxisome
      proliferator-activated receptor gamma agonist on macrophage activation.
AB  - Prostaglandin J2 metabolite 15-deoxy-delta(12,14)-prostaglandin J2 (15-PGJ2)
      appears to possess anti-inflammatory properties. Unlike other prostaglandins, it
      has no known plasma membrane receptor. Its effects have been thought to occur
      through activation of the nuclear peroxisome proliferator-activated receptor
      gamma (PPARgamma), but 15-PGJ2 may exhibit effects independent of PPARgamma. We
      hypothesized that 15-PGJ2 modulates macrophage (Mphi) mediator production by
      acting on cell signaling proteins upstream of PPARgamma. The effects of 15-PGJ2
      on bacterial endotoxin LPS-induced rat peritoneal Mphi mediator production were
      compared with those of a specific PPARgamma agonist, BRL 49653 (BRL), and to the
      eicosanoids prostaglandin D2 (PGD2) and cicaprost (CICA, a prostacyclin
      analogue). 15-PGJ2 inhibited LPS-induced production of NO, TNF-alpha, and
      thromboxane B2 (TxB2). Equimolar concentrations of PGD2 and CICA significantly
      inhibited LPS-stimulated TNF-alpha but not NO, and CICA increased TxB2
      production. BRL inhibited LPS-induced NO, but augmented LPS-induced TNF-alpha and
      TxB2. 15-PGJ2 also inhibited degradation of LPS-induced IkappaB alpha and
      phosphoactivation of ERK 1/2, but BRL had no significant effect on either
      protein. The cyclopentenone ring 2-cyclopenten-1-one also inhibited LPS-induced
      ERK 1/2 activation; however, neither 15-PGJ2 nor the cyclopentenone inhibited PMA
      induced ERK 1/2 activation. Inhibition of LPS-stimulated mediator production by
      15-PGJ2 differed from inhibition by PGD2, CICA, and BRL. The ability of 15-PGJ2
      to inhibit LPS-induced Mphi mediator production and cell signaling may occur in
      part through reactivity of its cyclopentenone ring.

PMID- 11310851
TI  - Inflammatory macrophage nuclear factor-kappaB and proteasome activity are
      inhibited following exposure to inhaled isobutyl nitrite.
AB  - A history of abuse of nitrite inhalants has been correlated with HIV
      seropositivity and Kaposi's sarcoma. A series of 14 daily, 45-min exposures of
      mice to 900-ppm isobutyl nitrite in an inhalation chamber reduced the number of
      peritoneal exudate macrophages (PEM) by 35% and the number of resident peritoneal
      macrophages (RPM) by 18%. Although the tumoricidal activity of RPM was not
      affected by the inhalant, the cytotoxicity of PEM was reduced by 26%. The
      induction of nitric oxide (NO) and the inducible NO synthase (iNOS) protein in
      PEM were inhibited by the inhalant to a similar extent. Inhibition of NF-kappaB
      activation in PEM from mice exposed to the inhalant corresponded to reduced
      degradation of the NF-kappaB inhibitor, IkappaB alpha. Proteasome-associated,
      enzymatic activity was compromised in PEM from inhalant-exposed mice, suggesting
      that inhaled isobutyl nitrite compromised macrophage, tumoricidal activity by
      inhibiting proteasomal degradation of the NF-kappaB inhibitor, IkappaB alpha.

PMID- 11310852
TI  - Expression of the apolipoprotein C-II gene during myelomonocytic differentiation
      of human leukemic cells.
AB  - Apolipoprotein C-II (apoC-II), which is known to activate lipoprotein lipase
      (LPL), was identified by ordered differential display (ODD)-polymerase chain
      reaction (PCR) as a cDNA fragment exhibiting a distinct increase in expression
      during 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced differentiation of
      promonocytic U937 cells into monocytes and macrophages. The amount of apoC-II
      mRNA expression detectable in U937 cells significantly increased and reached a
      maximum 24-48 h after treatment with 32 nM TPA. apoC-II mRNA was also detected in
      monocytic THP-1 cells but was not detected in promyelocytic HL-60 cells. In
      healthy human tissues, the most significant expression of apoC-II mRNA was in the
      liver. Although apoC-II mRNA expression was markedly up-regulated during the
      induced differentiation of HL-60 cells into monocytes and macrophages with 32 nM
      TPA, such expression was not induced during the differentiation of HL-60 cells
      into granulocytes with 1.25% dimethyl sulfoxide. These results suggest that human
      apoC-II expression is induced at the transcription level during myelomonocytic
      differentiation and may confer an important role to macrophages involved in
      normal lipid metabolism and atherosclerosis.

PMID- 11310853
TI  - Involvement of PKA, PKC, and Ca2+ in LPS-activated expression of the chicken
      lysozyme gene.
AB  - The lysozyme gene is activated in myelomonocytic HD11 cells in response to LPS.
      In this study, we described the involvement of LPS-activated signal transduction
      pathways in activation of the lysozyme gene. Pre-treatment of HD 11 cells with H
      89, H-7, TMB-8, or KN-93 resulted in inhibition of the LPS-enhanced lysozyme
      expression, suggesting that PKA, PKC, and Ca2+-dependent protein kinases
      participate in the LPS activation. CaMKII seems to be required for the processing
      of lysozyme transcripts. TPA and calcium ionophore A23187, when separately added
      to HD11 cells, stimulated the lysozyme expression effectively, and forskolin was
      ineffective. It is interesting that simultaneous treatment of cells with
      forskolin and calcium ionophore A23187 resulted in a potentiated increase in
      lysozyme mRNA expression, indicating a synergistic cooperation of PKA and Ca2+.
      This synergistic effect of PKA and Ca2+ was observed on the expression of a
      stably integrated CAT construct, controlled by the lysozyme promoter and the -6.1
      kb enhancer containing binding sites for C/EBP and NF-kappaB/Rel. Therefore, we
      discussed the role of C/EBPbeta(NF-M), CREB, and NF-kappaB/Rel as possible
      targets for phosphorylation mediated by PKA, PKC, and Ca2+.

PMID- 11310854
TI  - Signal transduction pathways for activation of extracellular signal-regulated
      kinase by arachidonic acid in rat neutrophils.
AB  - Phosphorylation of extracellular signal-regulated kinase (ERK) in response to
      arachidonic acid (AA) was rapid and transient, peaking at 1 min and disappearing
      after 3 min, and it was accompanied by an increase in ERK activity in rat
      neutrophils. We examined the upstream regulation of AA-stimulated ERK activation
      using one of the following signaling pathway inhibitors to pretreat rat cells:
      the ERK kinase inhibitor U0126 or PD98059, the G(i/o) inhibitor pertussis toxin
      (PTX), the tyrosine kinase inhibitor genistein, the phosphatidylinositol 3-kinase
      (PI3K) inhibitor wortmannin or LY294002, the Ca2+ chelator 1,2-bis(O
      aminophenoxy) ethane-N,N,N',N'-tetraacetic acid, or the phospholipase C (PLC)
      inhibitor U73122. All of these inhibitors attenuated AA-induced ERK activation.
      Activation of ERK was also effectively attenuated by the cyclooxygenase and
      lipoxygenase inhibitor BW755C and by the leukotriene biosynthesis inhibitor
      MK886, but the cyclooxygenase inhibitor indomethacin did not attenuate ERK
      activation. After exposing cells to three distinct protein kinase C (PKC)
      inhibitors, we found that Go6976 significantly attenuated ERK phosphorylation but
      potentiated ERK activity. Neither Go6983 nor GF109203X affected AA-induced
      responses. These data suggest that the lipoxygenase metabolite(s) produced
      mediates AA-stimulated ERK activation and that this effect is upstream regulated
      by PT-sensitive G protein, non-receptor tyrosine kinase, PI3K, and PLC/Ca2+
      signaling pathways in rat neutrophils.

PMID- 11310855
TI  - MCP-1 receptor binding affinity is up-regulated by pre-stimulation with MCP-1 in
      an actin polymerization-dependent manner.
AB  - Monocyte chemoattractant protein-1 (MCP-1) induces monocyte chemotaxis via
      interaction with the MCP-1 receptor CCR2. We found that MCP-1 binding to
      monocytic THP-1 cells was increased by pre-treatment with MCP-1. The amount of
      CCR2 mRNA and the cell-surface expression of CCR2 were not affected by MCP-1
      stimuli. In contrast, the MCP-1-treated THP-1 cells showed a sixfold increase in
      MCP-1 binding affinity compared with untreated cells. MCP-1 binding to CCR2B
      transfected HEK-293 cells was also enhanced by pre-treatment with MCP-1, and MCP
      1 binding affinity increased by sixfold. In both cell lines, the enhancement of
      MCP-1 binding by stimulation with MCP-1 was blocked by cytochalasin D, an
      inhibitor of actin polymerization. This effect of pre-treatment with MCP-1 is
      insensitive to pertussis toxin and partially blocked by U73122, an inhibitor of
      phospholipase C. These results demonstrate that the MCP-1 receptor binding
      affinity is up-regulated by MCP-1 stimuli in an actin polymerization-dependent
      manner.

PMID- 11310857
TI  - Just business.

PMID- 11310856
TI  - Regulation of L-selectin expression by a dominant negative Ikaros protein.
AB  - Ikaros family members play critical roles in hematopoietic development, yet
      molecules regulated by Ikaros proteins remain incompletely characterized. To
      determine the requirements for functional Ikaros proteins, we overexpressed Ik7,
      a dominant negative Ikaros protein, in human cell lines and hematopoietic
      progenitor cells. Ik7 is known to block the normal function of other Ikaros
      family members in human and mouse cells. Retroviral-mediated overexpression of
      Ik7 affected two distinct, migratory properties of the CEM T-cell line. Ik7 down
      regulated L-selectin cell-surface expression, an effect not a result of increased
      shedding but of a decrease in L-selectin mRNA levels. Ik7 also reduced the
      spontaneous migration of CEM T cells in 3-D collagen gels. A reduction in L
      selectin, cell-surface expression was also induced by Ik7 in CD34+ hematopoietic
      progenitor cells. In contrast, the Reh B cell line showed an up-regulation of L
      selectin, cell-surface levels when expressing Ik7. For the first time, this study
      defines an effect of Ikaros proteins in the control of migration-related
      properties and shows that intact Ikaros proteins are important in a cell type
      specific manner for the normal regulation of L-selectin expression.

PMID- 11310858
TI  - The adductor hallucis revisited.
AB  - To evaluate anatomic variability in the insertion of the adductor hallucis into
      the lateral sesamoid and proximal phalanx of the great toe and to evaluate the
      extent of release of the adductor hallucis tendon performed through an incision
      in the dorsal first-web space, we recorded the angle of hallux valgus in 42 fresh
      frozen specimens from human cadavers. An incision was made for a realignment of
      the soft tissues, dissecting down to the level of the intermetatarsal ligament. A
      loop of suture was placed around the identifiable adductor hallucis tendon
      through this incision along the lateral aspect of the lateral sesamoid. Then a
      plantar dissection removed all soft tissue to the level of the intermetatarsal
      ligament, adductor hallucis (transverse and oblique heads), lateral sesamoid, and
      lateral flexor hallucis brevis. The Insertion of these muscles into the proximal
      phalanx was evaluated. Specifically, we looked for separate slips of the adductor
      tendon inserting into the base of the proximal phalanx or separate insertions of
      the adductor tendon and the tendon of the flexor hallucis brevis muscle. In 33 of
      the 42 specimens, the entire adductor hallucis tendon had been isolated by the
      loop of suture through the incision in the dorsal first web. In eight of the
      remaining nine specimens, a small slip of the tendon (comprising less than 25% of
      its substance) had not been included. No specimen was found to have a separate
      slip of the adductor tendon inserting into the base of the proximal phalanx.
      Instead, all specimens were found to have only a conjoined insertion of fibers of
      the adductor hallucis and of the flexor hallucis brevis from the lateral sesamoid
      into the base of the proximal phalanx. We did not identify a separate tendon
      insertion into the proximal phalanx in any specimen. Therefore, great caution
      should be exercised in releasing an isolated insertion of the adductor tendon
      from the base of the proximal phalanx of the great toe since it may actually
      represent the conjoined insertion of the lateral flexor hallucis brevis tendon
      and the adductor tendon. We found that by simply releasing the adductor tendon
      from its insertion along the lateral aspect of the sesamoid, accomplished through
      an incision in the dorsal first web, that an adequate release was achieved in
      most specimens.

PMID- 11310859
TI  - Age-based outcomes of cheilectomy for the treatment of hallux rigidus.
AB  - The results of cheilectomy, performed on 67 consecutive patients with hallux
      rigidus resulting in primary extraarticular symptoms are presented. Four patients
      who underwent subsequent fusion were rated as failures. Follow-up evaluation,
      averaging 65 months (28-117) on 53 additional patients available for follow-up,
      revealed an average AOFAS score of 80. with 91% of the patients stating that they
      were currently better than before surgery. There was a statistically significant
      higher mean score (89) in patients over 60 years of age at the time of surgery.
      There were no differences between other age groups, preoperative grade, duration
      of symptoms, or length of follow-up. Cheilectomy should be the treatment of
      choice for hallux rigidus with predominantly extra-articular symptoms, especially
      in patients over 60 years of age.

PMID- 11310860
TI  - Dorsomedial cutaneous nerve syndrome: treatment with nerve transection and burial
      into bone.
AB  - Damage to the dorsomedial cutaneous nerve of the foot, which innervates the
      medial hallux, may occur with crush injury or iatrogenically with bunion surgery.
      Severe neuritic pain after bunion surgery may alert the surgeon that this small
      nerve has been damaged. The term "dorsomedial cutaneous nerve syndrome" is
      suggested for this condition, and nine patients with such forefoot presentations,
      all of which were unresponsive to nonoperative interventions, are described. The
      nerve had been either transected or bound in scar tissue; in these nine cases,
      the nerve was then resected and buried in the proximal aspect of the first
      metatarsal or the medial cuneiform. Most patients underwent an additional
      procedure (other than the nerve procedure), such as revision bunionectomy or
      arthrodesis, but all felt they could clearly delineate nerve pain from bone or
      joint pain. All patients experienced marked relief of their symptoms, usually
      within days after the surgery, and were satisfied with the results. The verbal
      analog pain score, on a scale of 0 (no pain) to 10 (pain requiring amputation),
      improved from a preoperative level of 8.6 to a postoperative level of 2.0.
      Resection and burial of this nerve appears to be a useful treatment for neuritis
      unresponsive to nonoperative measures.

PMID- 11310861
TI  - Surgical treatment for hallux valgus with painful plantar callosities.
AB  - We retrospectively reviewed the results of a distal soft-tissue procedure and
      proximal crescentic osteotomy of the first metatarsal combined with a proximal
      shortening osteotomy of the second and/or third metatarsal. This was in patients
      who had hallux valgus with painful plantar callosities. The review covered seven
      years of procedures (1989-1996) in 12 patients (14 feet) averaging 53 years of
      age. Average follow-up was 52 months. All patients had pain at the first
      metatarsophalangeal joint and had metatarsalgia preoperatively. At follow-up, 11
      feet had no pain at the first metatarsophalangeal joint, and three had some
      improvement of pain. Ten feet had no metatarsalgia, two had improvement of
      metatarsalgia, and two feet had transfer lesions postoperatively and required
      reoperation. The angle of hallux valgus averaged 40 degrees preoperatively and 13
      degrees postoperatively. The intermetatarsal angle averaged 18 degrees
      preoperatively and 6 degrees postoperatively. Mean decreases in length of the
      second and third metatarsal after surgery were 5.4 mm and 4.8 mm, respectively.
      Our results suggested that this combined procedure for hallux valgus with painful
      plantar callosities may be successful, in carefully selected patients.

PMID- 11310862
TI  - Single-stage talectomy and tibiocalcaneal arthrodesis as a salvage of severe,
      rigid equinovarus deformity.
AB  - Seven adult males with rigid, severe equinovarus deformities underwent single
      stage corrective surgery. The procedure included extensive soft tissue release,
      talectomy and tibiocalcaneal, calcaneocuboid, and tibionavicular fusion. All
      seven patients fused successfully at an average of 3.5 months with a plantigrade
      foot. All feet were stiff and had an average of 3.5 cm limb length discrepancy.
      All of the patients were satisfied with the surgery and would choose to have the
      procedure again. This small series represents one method of achieving a
      plantigrade foot in patients with severe, rigid equinovarus deformities.

PMID- 11310863
TI  - Biomechanical evaluation of the ability of casts and braces to immobilize the
      ankle and hindfoot.
AB  - We evaluated the ability of seven devices to immobilize a prosthetic ankle-foot
      complex against plantarflexion, dorsiflexion, inversion, and eversion forces: two
      casts (plaster of Paris and Fiberglas) and five removable braces (molded
      ankle/foot orthosis, composite boot brace, pneumatic boot walker, nonarticulating
      fracture boot, and ankle stirrup). Each device was applied to a prosthetic ankle
      foot complex and evaluated on a test frame for resistance to sagittal motion and
      coronal torque. Results showed that casts offered significantly (P < or = 0.05)
      more resistance to motion in all directions tested than did the braces. The
      resistance offered by the devices tested depends on the conformity of the device
      to the shape of the foot in that plane and the material properties of the device.
      Braces offer the advantage of being easily removed and reapplied. Different
      braces offer specific advantages and disadvantages in different planes tested,
      and immobilization selection should be individualized based on this information.

PMID- 11310864
TI  - Experimental flatfoot model: the contribution of dynamic loading.
AB  - The goal of this study was to determine if the application of muscle forces
      (simulating the dynamic phase of the midstance part of gait) had an effect on
      flatfoot deformity. We created a flatfoot model in each of seven cadaver foot
      specimens by grasping the Achilles, peroneus longus, peroneus brevis, flexor
      digitorum longus, and flexor hallucis longus tendons with soft-tissue vice clamps
      connected via wire cables to pneumatic cylinders. The experiment included four
      stages: 1) initial static axial loading; 2) axial loading after 3,000 load cycles
      (average, 735 N; range, 70 to 1400 N); 3) axial loading after releasing the
      spring ligament and plantar fascia; and 4) axial loading after an additional
      3,000 load cycles. At each stage, both static (with axial loading only) and
      dynamic (axial loading with tensioning of the tendons to simulate the muscle
      forces at midstance) conditions were evaluated radiographically. No change was
      observed between the static and dynamic conditions in the first two phases of the
      experiment. After the third phase, changes in the talar-first metatarsal angle
      and the height of the medial cuneiform were noted, particularly in the dynamic
      condition. These and additional radiographic changes were magnified in the fourth
      phase, but only in the dynamic condition. We concluded that, to create an
      effective flatfoot model, the medial structures, including the spring ligament
      and possibly the plantar fascia, must be severed. Cyclic loading of the foot
      further increased the arch flattening, and this effect was magnified by dynamic
      loading.

PMID- 11310865
TI  - Intra-articular load distribution in the human ankle joint during motion.
AB  - The rational treatment of injuries to the ankle is predicated on an understanding
      of biomechanics of the ankle. While several investigators have reported on three
      dimensional dynamic kinematics of the ankle and on the static distribution of
      pressure within the ankle, it has not been possible to measure intra-articular
      forces reliably under dynamic conditions. The assumption that the distribution of
      forces under dynamic conditions is well represented by statically determined
      forces has not been validated, leaving in question the applicability to dynamic
      conditions of data obtained under static conditions. This study characterizes an
      electro-mechanical thin-membrane force transducer with potential for intra
      articular use. The sensor was found to yield a reproducible linear response to
      loads experienced in the ankle, and was insensitive to both a moist environment
      and shearing forces. On the basis of these results, these force-transducers were
      placed in axially loaded cadaveric ankles that were either statically or
      dynamically cycled through a physiologic range of motion. In each of six
      specimens, sensors were secured to the medial and lateral malleolar articular
      surfaces, and to articular surfaces of the medial and lateral tibial plafond.
      Both medial and lateral malleolar-talar forces increased with dorsiflexion.
      Moving from plantarflexion to dorsiflexion caused an increase in lateral tibio
      talar load accompanied by a decrease in the medial tibio-talar loading. There was
      no significant hysteresis in force-distribution with respect to the direction of
      sagittal motion. There was no difference between the forces measured under static
      or dynamic conditions. This study validates the use of static loading
      methodologies in future studies of force-distribution. Our data in intact ankles
      closely corresponded to data on forces under dynamic conditions. Dorsiflexion
      caused an increase in both medially and laterally directed forces towards the
      malleoli. This is the first demonstration of such forces, which are responsible
      for the external rotation and lateral translation of the distal fibula that
      occurs in dorsiflexion of the ankle.

PMID- 11310866
TI  - The relationship between excessive pronation as measured by navicular drop and
      isokinetic strength of the ankle musculature.
AB  - EMG research has shown that excessive pronation affects the timing and magnitude
      of extrinsic muscle activity. This study was designed to investigate the
      relationship between excessive pronation and isokinetic strength of the ankle.
      The following measures were performed on 24 subjects (12 pronators, 12 normals)
      matched for gender and weight: 1) plantarflexion, dorsiflexion, inversion and
      eversion strength, both eccentrically and concentrically, determined by
      isokinetic peak torque at 30 degrees/sec; and 2) excessive pronation determined
      by navicular drop. Subjects with excessive pronation were found to have no
      difference in invertor strength, but decreased concentric plantarflexion strength
      when compared to normals. This finding agrees with biomechanical theory
      suggesting that a pronated foot is less rigid and generates less torque.
      Differences in strength ratios in excessive pronators were also observed and
      attributed to the decrease in plantarflexion strength.

PMID- 11310867
TI  - The effects of adult acquired flatfoot deformity on tibiotalar joint contact
      characteristics.
AB  - Changes in the tibiotalar contact characteristics were investigated using eight
      fresh frozen cadaver ankle specimens to further develop an established model of
      the acquired flatfoot deformity. The deformity was simulated by sectioning the
      tendons and ligaments of the ankle and foot that normally support the
      longitudinal arch. Axial loads of 1,350 N were applied to the foot in a neutral
      position in both the intact specimen and flatfoot model. The flatfoot condition
      resulted in significant lateral shifts of 5.28 mm in global contact area and
      11.26 mm in the location of peak pressure, and in a small but significant
      posterior shift of 1.14 mm in global contact area. The flatfoot condition also
      resulted in a significant, 35%, reduction in contact area. Significant increases
      in mean pressure, 14%, and peak pressure, 13%, were also found, but were not in
      proportion to the relatively large decrease in contact area. This suggests a
      transfer of load off of the talar dome. Increased loading of the lateral facet
      and fibula are suspected. The lateral shift in the contact region created a local
      increase in mean contact pressure that may be responsible for long term
      degenerative changes in patients with this deformity.

PMID- 11310868
TI  - Intraosseous bioabsorbable poly-L-lactic acid screw presenting as a late foreign
      body reaction: a case report.
AB  - A 17-year-old woman complained of a localized painful swelling in her foot 30
      months after internal fixation of a closed tarsometatarsal joint fracture with
      interfragmentary poly-L-lactic acid screws. Aspiration revealed a sterile
      abscess. Radiographs displayed an osteolytic lesion corresponding to a screw
      track in the first tarsometarsal joint. Formation of a draining sinus tract
      required surgical excision of a small granulomatous lesion. Histologic analysis
      found deposits of birefringent polymeric particles surrounded by a nonspecific
      foreign-body type reaction. This represents the first reported case of a draining
      sinus tract secondary to the use of polylactic acid screw fixation.

PMID- 11310869
TI  - Salter-Harris III stress fracture of the proximal first metatarsal: a case
      report.
AB  - An intraarticular, dorsal, proximal epiphyseal stress fracture (Salter-Harris
      III) of the first metatarsal was identified in a 14-year-old boy. Successful
      fracture healing was achieved with a rocker sole shoe modification and activity
      limitation.

PMID- 11310870
TI  - Lateral ankle reconstruction.

PMID- 11310871
TI  - Identification of the etiological agent for necrotizing scute disease in the
      Texas tortoise.
AB  - Epidermal lamellae (scutes) of the Texas tortoise, Gopherus berlandieri, from
      southern Texas (USA) were observed to be in various stages of necrosis, ranging
      from localized whitish blemishes to complete degradation of the external portion
      of the scute. Fusarium semitectum was consistently isolated from slivers of
      infected scute from tortoises. The fungus was not isolated from tortoises
      exhibiting no lesions. Confocal microscopy confirmed the presence of septate
      mycelia inside the scutes, and isolates of F. semitectum grown in the laboratory
      were successfully transferred to non-infected tortoises. Twenty-four tortoises
      maintained by two rehabilitators in southern Texas exhibited lesions; however,
      only one of 27 tortoises from Dimmit and Zavala counties was infected.

PMID- 11310872
TI  - Salmonelliasis in wildlife from Queensland.
AB  - During a 20 yr period (1978 to 1998), 233 isolates of Salmonella spp. were
      cultured from 179 wildlife animals (representing 25 species), 32 crocodile
      (Crocodylus porosus) eggs and six crocodile nesting sites, and represented 59
      different serotypes. Salmonella serotype Virchow, the major serotype infecting
      humans in north Queensland, (Australia) was common in macropodids, but was not
      found in reptiles and was isolated only once from cane toads (Bufo marinus).
      Investigations of human cases of salmonellosis should include simultaneous
      studies on wild and domestic animals in contact with the case.

PMID- 11310873
TI  - Campylobacteriosis, salmonellosis, and shigellosis in free-ranging human
      habituated mountain gorillas of Uganda.
AB  - For conservation purposes and due to growing ecotourism, free-ranging mountain
      gorillas (Gorilla gorilla beringei) have been habituated to humans. Fecal
      specimens (n = 62) collected in January 1999 from mountain gorillas of the Bwindi
      and Mgahinga National Parks, Uganda, were tested for Campylobacter spp.,
      Salmonella spp., and Shigella spp., and the overall prevalence of infection was
      19%, 13%, and 6%, respectively. The prevalence of positive specimens was not
      related to the year of habituation of a gorilla group to humans. Campylobacter
      spp., Salmonella, and Shigella spp. infections were not distributed equally among
      the age classes of gorillas; most of the enteropathogens (80%), and all Shigella
      spp. organisms, S. sonnei, S. boydii, and S. flexneri, were isolated from
      subadults and adult gorillas with ages ranging from 6.0 to 11.9 yr. The
      prevalence of Campylobacter spp. and Salmonella spp. infections among human
      habituated gorillas has doubled during the last 4 yr, and isolation of Shigella
      spp. for the first time from mountain gorillas, may indicate enhanced
      anthropozoonotic transmission of these enteropathogens.

PMID- 11310874
TI  - Diagnosis and treatment of conjunctivitis in house finches associated with
      mycoplasmosis in Minnesota.
AB  - An ongoing outbreak of Mycoplasma gallisepticum-associated conjunctivitis in
      house finches (Carpodacus mexicanus) that began in 1994 in the eastern United
      States has been spreading westward. House finches presenting with the clinical
      signs of M. gallisepticum-associated conjunctivitis were first seen at the
      Wildlife Rehabilitation Center of Minnesota (Minnesota, USA) in July of 1996, and
      42 cases were admitted from 26 December 1996 to 10 August 1997. A nested PCR was
      designed for sensitive and specific detection of the presence of the organism.
      Twelve birds were treated with oral enrofloxacin (15 mg/kg, twice daily for 21
      days) and ophthalmic gentamicin (twice daily for 21 days). All treated birds
      showed resolution of clinical signs. Following treatment, finches were held for
      up to 6 mo and tested for the presence of M. gallisepticum by culture and nested
      polymerase chain reaction (PCR). Eight of twelve finches (67%) were positive for
      M. gallisepticum by nested-PCR and four (33%) were positive by culture. The
      results suggest that oral enrofloxacin and opthalmic gentamicin are not an
      effective treatment for the eradication of M. gallisepticum in house finches.
      Further, the results show that nested PCR is an effective method for detection of
      M. gallisepticum in house finches and was more sensitive than culture.

PMID- 11310875
TI  - Nasal and cloacal bacteria in free-ranging desert tortoises from the western
      United States.
AB  - Aerobic bacteria were collected from three free-ranging desert tortoise (Gopherus
      agassizii) populations in the eastern Mojave Desert (Arizona, Utah; USA) from
      1989 to 1993, and from two free-ranging populations in the central Sonoran Desert
      (Arizona, USA) from 1990 to 1994. Six species of nasal bacteria and 18 species of
      cloacal bacteria were identified. At least one potential pathogen was found in
      the nasal cavity (Pasteurella testudinis), and at least two potential pathogens
      in the cloaca (Pseudomonas spp., Salmonella spp.).

PMID- 11310876
TI  - Prevalence of bovine tuberculosis in African buffalo at Kruger National Park.
AB  - Bovine tuberculosis (BTB) was first detected in Kruger National Park (KNP) in a
      single African buffalo (Syncerus caffer) in 1990. In 1991/1992, 2,071 African
      buffalo were examined for BTB as part of a culling program that removed animals
      from all known herds in KNP. The prevalence of BTB in 1991/1992 was estimated to
      be 0%, 4.4% (+/-0.6%), and 27.1% (+/-1.4%), in the north, central, and south
      zones of KNP, respectively. In 1998, a stratified, two-stage cluster sampling
      method was used to estimate that the prevalence of BTB was 1.5% (+/-2.5%), 16%
      (+/-5.3%), and 38.2% (+/-6.3%), in the north, central, and south zones,
      respectively. This represented a significant increase in prevalence (P < or =
      0.05) in the south and central zones, but not in the north zone. Continued
      monitoring of BTB in KNP is important for understanding disease transmission
      risks, potential population effects, and the efficacy of disease management
      strategies. The methodology and sample sizes used in 1998 are appropriate for
      future BTB monitoring in KNP.

PMID- 11310877
TI  - Emergency response to raccoon rabies introduction into Ontario.
AB  - During 15 July to 4 October, 1999, rabies control programs were implemented with
      the objective being to contain the first three confirmed cases of raccoon rabies
      in Canada. The strategy, called point infection control (PIC) involved the use of
      three tactics: population reduction (PR), trap-vaccinate-release (TVR) and oral
      rabies vaccination with baits (ORV), to control the spread of raccoon rabies. A
      total of 1,202 raccoons (Procyon lotor) and 337 skunks (Mephitis mephitis) were
      captured and euthanized using 24,719 trap-nights in the three PR zones around the
      location of the three rabies cases, near Brockville, Ontario. That represented an
      83% to 91% reduction in the raccoon populations in an approximate 225 km2 area
      around the three rabies cases. Raccoon density in the PR zones declined from 5.1
      7.1/km2 to 0.6-1.1/km2 following control. All tested specimens were negative for
      rabies by the fluorescent antibody test (FAT). In addition, 1,759 raccoons and
      377 skunks were intramuscularly vaccinated against rabies and released using
      27,956 trap-nights in an approximate 485 km2 TVR zone implemented outside of the
      PR zones. A total of 856 cats from both PR and TVR areas were also captured,
      vaccinated and released. Cost for the three PIC operations was $363,000.00 Cdn or
      about $500.00 Cdn/km2. To further contain the outbreak, about 81,300 baits
      containing Raboral V-RG oral rabies vaccine were aerially distributed on 8 and 27
      September 1999, to create an 8 to 15 km wide buffer zone (1,200 km2 area) of
      vaccinated raccoons immediately beyond the PR and TVR zones. This was the first
      time that V-RG was used in Canada to orally vaccinate free ranging raccoons
      against rabies. Baiting costs were $241,000.00 Cdn or about $200.00 Cdn/km2
      including post baiting assessment costs. As of 31 August, 2000, thirty-five
      additional cases (38 in total) of raccoon rabies have occurred in the control and
      vaccination zones. This number is far below the level of rabies prevalence in USA
      jurisdictions where raccoon rabies was epizootic. In the future, PIC
      methodologies will continue to be used in Ontario to contain isolated cases of
      raccoon rabies.

PMID- 11310878
TI  - Do unusual site-specific population dynamics of rodent reservoirs provide clues
      to the natural history of hantaviruses?
AB  - Between January 1995 and November 1997, longitudinal mark-recapture studies of
      rodent hosts of hantaviruses in a disturbed microhabitat within a shortgrass
      prairie ecosystem in southeastern Colorado (USA) were conducted. The site was
      distinguished by edaphic and floristic characteristics unique to this area and
      associated with historical land use patterns, as well as the year-around
      availability of water from a functioning windmill. Populations of two common
      rodent species that are hosts for hantaviruses, Peromyscus maniculatus and
      Reithrodontomys megalotis, had unusually rapid turnover, a younger age structure,
      and a much lower prevalence of antibody to Sin Nombre virus than did populations
      at nearby sites in more typical shortgrass prairie and canyon habitats. Based on
      these findings, we suggest that a stable resident population of the reservoir is
      critical to the maintenance of hantaviruses at a given site, and we hypothesize
      that long-lived, persistently infected rodents are the principal transseasonal
      reservoir of hantaviruses.

PMID- 11310879
TI  - Venereal transmission of pseudorabies viruses indigenous to feral swine.
AB  - Between 1995 and 1998, we designed a series of studies in which we attempted to
      determine the main routes of transmission involved in the natural infection of
      pseudorabies virus (PRV) indigenous to free-ranging feral swine (Sus scrofa).
      Naturally infected feral sows transmitted the infection to uninfected feral
      boars, with which they had been commingled for a 6-wk period. Pseudorabies virus
      was isolated from boar preputial swabs, but not from nasal swabs. Three of the
      same PRV-infected feral sows did not transmit the infection to domestic boars
      during a 16 wk commingling period, despite the fact that they became pregnant.
      Feral boars, naturally infected with PRV transmitted the virus to domestic gilts
      while penned together during 6 wk. Pseudorabies virus was isolated from vaginal
      swabs, but not from nasal swabs of gilts, after 2 and 3 wk of commingling. When
      the same infected boars were commingled with either feral or domestic boars for
      13 wk, PRV transmission did not occur. None of the exposed boars developed
      neutralizing antibodies or yielded virus from their preputial or nasal swabs. Our
      results indicate that PRV indigenous to feral swine is preferentially transmitted
      to feral or domestic swine of the opposite sex by the venereal route. This mode
      of transmission differs from that seen in the natural transmission of PRV
      prevalent in domestic swine, where contaminated secretions, excretions and
      aerosols are responsible for the spread of the virus. Based on these results, we
      feel that as long as feral swine do not come into direct contact with domestic
      swine, PRV-infected feral swine probably pose only a limited risk to the success
      of the National Pseudorabies Eradication Program. The fact that PRV is usually
      transmitted from feral to domestic swine at the time of mating would indicate
      that the isolation of domestic herds by the use of a "double fence," should be
      adequate protection against reinfection with PRV.

PMID- 11310880
TI  - Two novel alphaherpesviruses associated with fatal disseminated infections in
      Atlantic bottlenose dolphins.
AB  - Two immature female bottlenose dolphins (Tursiops truncatus) were found stranded
      on the Atlantic coast of the USA. Necropsy and histopathologic examination of
      both dolphins demonstrated acute necrotizing lesions in multiple organ systems.
      Commonly seen in these lesions were cells with enlarged nuclei that contained
      single 4 to 6 microm diameter homogeneous eosinophilic inclusion bodies that were
      often surrounded by a clear halo. Ultrastructural examination revealed that
      intranuclear inclusions contained 90 to 110 nm diameter viral particles with
      electron-dense cores and hexagonal profiles. Viral particles were also present in
      the cytoplasm, and these were surrounded by variably electron-dense envelopes.
      Enveloped virions were 140 nm in diameter. Polymerase chain reactions targeting
      the DNA polymerase and terminase genes of herpesviruses were carried out on
      unfixed tissues of both animals, and analysis of the DNA products indicated the
      presence of two novel alphaherpesviruses. The gross, histologic, ultrastructural,
      and molecular genetic findings indicate disseminated herpesviral infections, and
      support the conclusion that the alphaherpesviruses caused the deaths of the two
      dolphins. This is the first report of disseminated herpesviral infection in
      cetaceans.

PMID- 11310881
TI  - Isolation of bovine viral diarrhea virus from a free-ranging mule deer in
      Wyoming.
AB  - A noncytopathic type 1a bovine viral diarrhea virus (BVDV) was isolated from a
      free-ranging yearling female mule deer (Odocoileus hemionus) from northwestern
      Wyoming (USA). The mule deer was emaciated, weak, and salivating, and
      Arcanobacterium pyogenes was cultured from lung abscesses. Bovine viral diarrhea
      virus was isolated from lung, however, BVDV antigen was not detected by
      immunohistochemistry. The BVDV genotype was determined by reverse transcriptase
      polymerase chain reaction and the RNA sequences from the 5'UTR and E2 genes
      compared with sequences of a type 1a BVDV isolated from cattle from the same area
      as the deer. The sequences from the deer BVDV were distinct from those of the
      bovine type 1a BVDV, but similar to other bovine type 1a BVDVs. Seventy-four
      (60%) of 124 sera collected from mule deer in this area had serum neutralizing
      antibody titers to type 1a BVDV of > or = 1:32. The high prevalence of
      seropositive mule deer and isolation of BVDV suggests that this virus circulates
      in the mule deer population. The isolate described in this report is the second
      reported BVDV isolate from free-ranging deer in North America and the first from
      a mule deer.

PMID- 11310882
TI  - Morbidity-mortality factors and survival of an urban coyote population in
      Arizona.
AB  - The health of coyotes (Canis latrans) in urban areas has not been studied. Our
      objectives were to assess the health of coyotes in Tucson (Arizona, USA) by
      determining the prevalence of antibodies to selected pathogens, estimating
      survival rates, and identifying sources of mortality. We drew blood from 22
      coyotes to evaluate the prevalence of heartworm (Dirofilaria immitis) antigens,
      and antibodies to canine distemper virus (CDV), infectious canine hepatitis
      (ICH), canine parvovirus (CPV), and seven serovars of Leptospira interrogans. We
      trapped and radiocollared 19 coyotes to determine survival rates. We performed
      necropsies on 19 coyotes to quantify their general health, the presence of
      internal and external parasites, and causes of mortality. No coyotes tested
      positive for heartworm antigens. The prevalence of antibody to CDV, ICH, and CPV
      was 27, 50, and 100%, respectively. Twenty-seven percent of coyotes tested
      positive for one of five serovars of L. interrogans. The diseases for which
      coyotes in Tucson possessed antibodies appear to be enzootic in the population.
      The annual survival rate of coyotes was 0.72. Eleven necropsied coyotes were
      killed by cars, five coyotes were hit by cars, two were killed by a trapper, and
      the cause of death for one coyote was unknown. Coyotes in Tucson appear to be
      exposed to the viral, bacterial, and parasitic infections common in many coyote
      populations, but humans are the major source of mortality.

PMID- 11310883
TI  - Failure of tetracycline as a biomarker in batch-marking juvenile frogs.
AB  - Recent widespread amphibian declines call for better techniques to assess
      population dynamics. Tetracycline as a biomarker in capture-recapture studies is
      one technique used successfully in fish, reptiles, and mammals. A two-phase
      experimental study was conducted to evaluate tetracycline as a biomarker in green
      frogs (Rana clamitans) and pickerel frogs (Rana palustris). In the first
      experimental phase tadpoles were exposed to water containing either 250 mg/l or
      500 mg/l tetracycline for a period of 24 hr. During the second phase, juvenile
      frogs were exposed to tetracycline in water at 500 mg/l or given injections of
      tetracycline at the dose rate of 100 mg/kg body weight. At selected times several
      weeks later, under tricaine methanesulfonate anesthesia, a toe was surgically
      excised from each animal, sectioned and viewed under an ultraviolet microscope.
      No significant differences were found between the various treatments and control
      animals (untreated). Therefore, the use of tetracycline as a biomarker in anurans
      using these techniques is not recommended.

PMID- 11310884
TI  - Ceruloplasmin as an indicator of copper reserves in wild ruminants at high
      latitudes.
AB  - Northern ungulates must establish trace mineral reserves when forage is available
      in spring and summer to sustain biochemical activities through the long winter.
      Copper (Cu), zinc (Zn) and iron (Fe) reserves were measured in the serum,
      digestive tract, liver, and kidney of six male caribou and reindeer (Rangifer
      tarandus) fed a complete pelleted ration. Dry matter content and absolute amounts
      of Cu, Zn and Fe were highest in the liver. Digesta contents of Cu and Zn were
      greatest in the rumen but dry matter concentrations were greatest in the cecum
      reflecting the high levels of Cu and Zn in the diet. Serum ceruloplasmin (an
      oxidase containing Cu) activity was related to liver copper in captive reindeer
      and caribou (P < 0.05, r2 = 0.82) during spring and winter but not during the
      rut. Michaelis-Menten kinetics of ceruloplasmin were measured in sera from
      captive reindeer, muskox (Ovibos moschatus) and moose (Alces alces) (n =
      3/species). Maximum velocities (VMAX) were 42, 20 and 9 (IU x L(-1)); kM were
      0.38, 0.55 and 0.62 (mM) for muskox, reindeer and moose respectively. Wild
      caribou (n = 3) from the Teshekpuk herd and moose (n = 3) from the Colville River
      had lower VMAX (7 IU x L(-1)) and higher km (1.9 mM) than their captive
      conspecifics. These kinetic parameters probably reflect differences in
      ceruloplasmin structure between species as well as differences in tissue reserves
      between populations within each species. Serum ceruloplasmin activity and
      kinetics can provide a non-lethal alternative to direct measures of hepatic Cu
      reserves in wild and captive populations. However, the method requires validation
      for the effects of sex, season, development and disease in each species.

PMID- 11310885
TI  - Serum chemistry of the minke whale from the northeastern Atlantic.
AB  - Serum samples were collected from 42 harpooned minke whales (Balaenoptera
      acutorostrata) during commercial whaling off the coast of northern Norway (1997
      and 1998) and analyzed for serum chemistry parameters in order to find clinical
      reference values for the northeastern Atlantic stock of this species. Mean and
      median values, as well as standard deviation and 90% central range, are presented
      for 28 different serum chemistry parameters. Lipemia is a common finding in
      marine mammals such as the minke whale, and chemical analysis of lipemic serum
      samples may produce artifacts. We found statistically significant elevated values
      of total protein, globulin, aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), sodium and chloride in strongly-lipemic compared to non
      lipemic samples, all which may be artifacts due to interference of lipids with
      the methods used for analysis. In addition, we found significantly elevated
      levels of creatin kinase, lactate dehydrogenase (LDH), urea, uric acid and
      triglycerides, as well as a decrease in creatinine in the strongly lipemic
      samples. Reanalyzing serum samples after twelve mo storage at -20 C (n = 13)
      revealed reduction in the serum concentration of the enzymes ALT (42%), alkaline
      phosphatase (ALP; 10%), LDH (19%), gamma glutamyl transferase (17%) and amylase
      (11%), as well as for triglycerides (9%) and non-esterified fatty acids (16%). It
      is crucial that serum chemistry analysis is performed without delay after
      sampling. Possible changes in the values of some parameters due to the presence
      of high amounts of lipids or long term storage of samples must be considered when
      interpreting results from serum chemistry analysis in these animals.

PMID- 11310886
TI  - Hypodermosis of red deer in Spain.
AB  - From February 1998 to January 1999, 106 red deer in the Autonomic Organism
      National Park "Quintos de Mora" (Toledo, central Spain) were evaluated to
      determine the prevalence and dynamics of infection with Hypoderma sp. by
      detection of subcutaneous larvae. Between six and 13 deer shot in selective
      hunting were examined monthly. Hypoderma sp. larvae were detected throughout the
      period except in June, July and August of 1998. Excluding the period during which
      no subcutaneous larvae were detected, the number of animals sampled was 80 (52
      males and 28 females), belonging to three age classes: 12 calves (<1-yr-old), 19
      yearlings (1-yr-old), and 49 adults (2- to 10-yr-old). All the third instar (L3)
      collected were identified as H. actaeon. Total prevalence during the period of
      larval detection was 61%. Prevalence in yearling and adult deer shot during the
      official hunting season was 89%. Monthly prevalence increased from September to
      January and decreased from February to May. In September and October, a small
      percentage of larvae were classified as first instar (L1). The rest of larvae
      collected between September and December were second instar (L2). Third instar
      (L3) predominated in January and February and was the only stage collected from
      March to May. Intensity ranged from 1 to 145 larvae. Intensities were >100 larvae
      in 6% of animals. Possible relationships of intensity or prevalence of infection
      with sex or age of the animals were evaluated. Significant differences in
      prevalence were observed among different host age classes. Prevalence was higher
      in yearlings (84%) than in adults (63%) and lowest in calves (17%).

PMID- 11310887
TI  - Duck plague epizootics in the United States, 1967-1995.
AB  - In 1967, the first confirmed diagnosis of duck plague (DP) in the USA was made
      from pekin ducks (Anas platyrhynchos domesticus) on commercial duck farms on Long
      Island, New York. Within 10 mo, DP was confirmed as the cause of death in
      migratory waterfowl on a Long Island bay. This paper reviews 120 DP epizootics
      reported from 1967 to 1995 that involved waterfowl species native to North
      America or were reported in areas with free-flying waterfowl at risk. Duck plague
      epizootics occurred in 21 states with the greatest number reported in Maryland
      (29), New York (18), California (16), and Pennsylvania (13). The greatest
      frequency of epizootics (86%) was detected during the months of March to June. At
      least 40 waterfowl species were affected with the highest frequency of epizootics
      reported in captive or captive-reared ducks including muscovy ducks (Cairina
      moschata) (68%), mallard ducks (A. platyrhynchos) (18%) and black ducks (A.
      rubripes) (14%). The greatest number of waterfowl died in three epizootics that
      involved primarily migratory birds in 1967 and 1994 in New York (USA) and 1973 in
      South Dakota (USA). The greatest number of DP epizootics reported since 1967
      appear to have involved flocks of non-migratory rather than migratory waterfowl;
      therefore, in our opinion it remains unknown if DP is enzootic in either non
      migratory or migratory waterfowl.

PMID- 11310888
TI  - Detection of aflatoxin-contaminated grain by three granivorous bird species.
AB  - Supplemental feeding of game species and the use of backyard feeders to attract
      avian wildlife are common practices throughout the United States. However, these
      activities may expose wildlife to aflatoxins. We tested the hypothesis that wild
      birds would avoid consuming aflatoxin-contaminated feed. Individual northern
      bobwhites (Colinus virginianus), white-winged doves (Zenaida asiatica), and green
      jays (Cyanocorax yncas) were presented with feeders that had four compartments,
      which contained milo that was contaminated with aflatoxin levels of 0, 100, 500,
      and 1,000 microg/kg, respectively. Feed remaining was weighed at 6, 12, 18, 24,
      36, 48, 60, and 72 hr after the initiation of the trial. White-winged doves and
      northern bobwhites did not avoid contaminated feed. However, green jays selected
      against aflatoxin-tainted grain. Because white-winged doves and northern
      bobwhites did not avoid contaminated feed, the risk of exposure to this
      potentially hazardous toxin exists for these species.

PMID- 11310889
TI  - Theobromine intoxication in a red fox and a European badger in Sweden.
AB  - A red fox (Vulpes vulpes) and a European badger (Meles meles) were found dead on
      a golf-course in October 1997 near Stockholm (Sweden). At necropsy, both animals
      were obese and the main finding was acute circulatory collapse. Theobromine
      intoxication was suspected as chocolate waste was available at a nearby farm and
      no other cause of death could be detected. Gastric contents and samples of liver
      from both animals were analyzed by reversed-phase high pressure liquid
      chromatography for the presence of methylxanthines. Theobromine and caffeine were
      detected in gastric contents and theobromine was identified in the liver samples
      from both animals. This appears to be the first report of theobromine
      intoxication in the red fox and the European badger.

PMID- 11310890
TI  - Acid-base status and blood gas arterial values in free-ranging sika deer hinds
      immobilized with medetomidine and ketamine.
AB  - Ten free-ranging female sika deer (Cervus nippon) were captured to obtain the
      reference values for acid-base status and blood gas when immobilized with the
      combination of medetomidine and ketamine. The mean +/- SE of PaCO2, PaO2, and
      HCO3- were 58.1 +/- 6.1 mmHg, 58.8 +/- 6.4 mmHg, and 36.0 +/- 4.4 mmol/l,
      respectively. Although acidosis and alkalosis occurred in three and two animals,
      respectively, no serious conditions were observed. The blood values, however,
      suggest that some degree of hypoxemia and respiratory acidosis with metabolic
      alkalosis are developed. The trapped deer showed a significantly higher than
      normal rectal temperature reflective of exertion.

PMID- 11310891
TI  - Hematological and plasma biochemical values of the greater glider in Australia.
AB  - Reference hematological and plasma biochemical values are presented for the
      greater glider (Petauroides volans) at Tumut (southeastern New South Wales,
      Australia). Nineteen animals were sampled during a capture period of 1 wk in
      August 1999. Values for red cell counts were significantly higher in male animals
      (mean +/- SE; males: 5.6 +/- 0.1; females: 5.2 +/- 0.1). Young animals had higher
      white cell counts than older ones (mean +/- SE; young: 4.9 +/- 0.4; older: 2.8 +/
      0.4). Lymphocytes were the predominant white blood cell type in this species.

PMID- 11310892
TI  - Effects of whirling disease on selected hematological parameters in rainbow
      trout.
AB  - Hematological responses to whirling disease in rainbow trout (Oncorhynchus
      mykiss) were investigated. Two-mo-old fingerling rainbow trout were exposed to
      cultured triactinomyxon spores of Myxobolus cerebralis at 9,000 spores/fish in
      December, 1997. Twenty-four wks post-exposure, fish were taken from infected and
      uninfected groups for peripheral blood and cranial tissue sampling. Histological
      observations on cranial tissues confirmed M. cerebralis infection in all exposed
      fish. Differences in hematological parameters between the two groups included
      significantly lower total leukocyte and small lymphocyte counts for the infected
      fish. No effects on hematocrit, plasma protein concentration, or other
      differential leukocyte counts were noted.

PMID- 11310893
TI  - Adenocarcinoma of the small intestine in a ringed seal from Hudson Bay.
AB  - Nineteen wild ringed seals (Phoca hispida) were killed in winter 1999 to assess
      the health status of seals harvested in eastern Hudson Bay (Quebec, Canada). One
      of these seals, an 11-yr-old male, had a poorly differentiated adenocarcinoma
      that severely constricted the lumen of the distal small intestine. The tumor was
      characterized by proliferation of polygonal epithelial cells that formed closely
      packed acini and cords. This appears to be the first reported case of
      adenocarcinoma of the small intestine in Pinnipedia.

PMID- 11310894
TI  - Capture and immobilization of wild brown palm civets in Western Ghats.
AB  - A mixture of 15 mg/kg body weight ketamine hydrochloride (KE) and 1.5 mg/kg body
      weight xylazine hydrochloride (XY) was used to successfully immobilize free
      ranging brown palm civets (Paradoxurus jerdoni). Between March 1998 and June
      1999, 10 immobilizations of 7 individuals were carried out in tropical
      rainforests of the Kalakad-Mundanthurai Tiger Reserve (India). Five males and two
      females were captured in Havahart live traps, using banana as bait. The mean
      dosage for the animals, whose weight (mean +/- SD) was 2.4 kg +/- 0.8 was 36.0 +/
      11.0 mg KE and 3.7 +/- 1.1 mg XY, administered intramuscularly. Mean time for
      lateral recumbency was 6.1 +/- 3.78 min (n = 10) and the mean time taken for
      complete recovery was 84.9 +/- 28.8 min (n = 9). Recovery was gradual and no
      fatalities or injuries occurred during the operation. The drug combination used
      was effective and has the potential for immobilizing other viverrids.

PMID- 11310895
TI  - Intraocular pressure and tear production in captive eland and fallow deer.
AB  - Applanation tonometry was used to estimate intraocular pressure (IOP) and
      Schirmer tear test (STT) I was used to estimate tear production in both eyes of
      12 juvenile elands (Taurotragus oryx) and one eye each of 15 Asian fallow deer
      (Dama mesopotamica). Mean (+/- standard deviation) IOP was 14.6 +/- 4.0 mm Hg in
      the eland and 11.9 +/- 3.3 mm Hg in the deer. Mean tear production was 18.7 +/-
      5.9 mm/min in the eland and 10.5 +/- 6.5 mm/min in the deer. The large variation
      in IOP between two members of the family Bovidae, the elands reported here and
      the Thomson gazelle (Gazella thomsoni) for which we previously reported a mean
      pressure of 7.6 mm Hg, illustrates the need to establish reference values for
      each species. Tear production may be influenced by the species' natural habitat.

PMID- 11310896
TI  - Serologic evidence of hantavirus infection in sigmodontine rodents in Mexico.
AB  - Antibodies to hantaviruses in two species of sigmodontine rodents (Peromyscus
      maniculatus and Reithrodontomys sumichrasti) collected in central Mexico are
      reported. Peromyscus maniculatus, a common species throughout much of Mexico, is
      the reservoir of Sin Nombre virus (SNV), the etiologic agent of the great
      majority of cases of hantavirus pulmonary syndrome (HPS) in North America.
      Although the identity of the virus detected in P. maniculatus in Mexico could not
      be determined by these serologic results, our findings suggest that SNV may occur
      throughout the range of P. maniculatus in North America. If true, the failure to
      identify HPS in Mexico is not due to the absence of pathogenic hantaviruses in
      Mexico.

PMID- 11310897
TI  - Neutralizing antirabies antibodies in urban terrestrial wildlife in Brazil.
AB  - The prevalence of rabies neutralizing antibodies (NA) in sera of wild animals
      from Sao Paulo City (Brazil) was investigated using the Rapid Fluorescent Focus
      Inhibition Test between 1994 and 1997. Sera from 547 specimens were examined.
      Marsupials represented 45% of the sample and primates 37%; carnivores, rodents,
      deer and edentates represented 6, 6, 3 and 2%, respectively. The overall
      prevalence of NA was 14%. The prevalence of NA was 18% in primates; whereas in
      marsupials, carnivores, edentates and rodents it was 13, 9, 8 and 6%,
      respectively. The stratification according to sex, age, and site of capture of
      the marsupials and primates showed a small predominance in males versus females
      and a large predominance of adults versus juveniles. The same relationship was
      seen in specimens captured near human habitations versus specimens captured in
      their own habitat. It is evident that there is circulation of rabies virus in
      wild animals, which are not recommended as pets since they represent a potential
      risk of exposure to rabies virus for both humans and domestic animals.

PMID- 11310898
TI  - Mortality in captive elk from salmonellosis.
AB  - Salmonella typhimurium DT104 infections of captive elk (Cervus elaphus nelsoni)
      calves resulted in mortality in eight of 13 affected calves. Salmonellosis in
      these elk calves was characterized by diarrhea, fever, lethargy, inappetence and
      depression, and death usually ensued within 72 hr of initial clinical signs.
      Affected calves did not respond to antibiotic and fluid therapy. The source of
      the bacteria likely was one or more of the calves when they were captured in the
      wild at less than 5 days of age. In our captive holding facility, the disease
      spread quickly and was difficult to control. Phage typing, pulsed field gel
      electrophoresis, antibiotic sensitivity testing, and plasmid profiles determined
      that this Salmonella sp. strain was the epidemic strain common to cattle, sheep
      and humans.

PMID- 11310899
TI  - Hematozoa of hatch-year common mergansers from Michigan.
AB  - Fifty-five hatch-year common mergansers (Mergus merganser) were sampled for
      hematozoa from Douglas Lake (Michigan, USA) on 17 July 1995. Forty-one (75%) were
      infected with hematozoa. Haemoproteus greineri and Leucocytozoon simondi were
      common, infecting 28 (51%) and 26 (47%) common mergansers, respectively.
      Plasmodium circumflexum infected two (4%) birds. The common merganser is a new
      host record for H. greineri and P. circumflexum. Intensity data indicate possible
      negative interspecific interaction between H. greineri and L. simondi.

PMID- 11310900
TI  - Pneumocystosis in wild small mammals from California.
AB  - Cyst forms of the opportunistic fungal parasite Pneumocystis carinii were found
      in the lungs of 34% of the desert shrew, Notiosorex crawfordi (n = 59), 13% of
      the ornate shrew, Sorex ornatus (n = 55), 6% of the dusky-footed wood rat,
      Neotoma fuscipes (n = 16), 2.5% of the California meadow vole, Microtus
      californicus (n = 40), and 50% of the California pocket mouse, Chaetodipus
      californicus (n = 2) caught from southern California between February 1998 and
      February 2000. Cysts were not found in any of the harvest mouse, Reithrodontomys
      megalotis (n = 21), California mouse, Peromyscus californicus (n = 20), brush
      mouse, Peromyscus boylii (n = 7) or deer mouse, Peromyscus maniculatus (n = 4)
      examined. All infections were mild; extrapulmonary infections were not observed.
      Other lung parasites detected were Hepatozoon sp./spp. from M. californicus and
      Notiosorex crawfordi, Chrysosporium sp. (Emmonsia) from M. californicus, and a
      nematode from S. ornatus.

PMID- 11310901
TI  - The safety and efficacy of propofol containing EDTA: a randomised clinical trial
      programme focusing on cation and trace metal homeostasis in critically ill
      patients.

PMID- 11310902
TI  - The recent development of propofol (DIPRIVAN).

PMID- 11310903
TI  - Propofol-containing sedatives increase levels of parathyroid hormone.
AB  - OBJECTIVE: To evaluate the effects of propofol and propofol containing disodium
      edetate (ethylenediaminetetraacetic acid [EDTA]) on the parathyroid-calcium axis
      in normal subjects. DESIGN: Randomised, double-blind, age-stratified, crossover
      trial. SETTING: Single centre. PATIENTS: A total of 50 healthy subjects.
      INTERVENTIONS: Each subject was randomised to receive propofol or propofol
      containing EDTA on day 1 and the alternate treatment between days 15 and 29, with
      a 2-week wash-out period in between. On the day of treatment, subjects received a
      bolus of trial medication (1 or 2 mg/kg) followed by a 60-minute observation
      period. At the end of 60 minutes, subjects received trial medication infused for
      60 minutes at 1 of 4 randomised infusion rates (25, 50, 100, or 200 microg/kg per
      min). Subjects were monitored for an additional 60 minutes following the
      infusion. MEASUREMENTS AND RESULTS: Blood pressure, heart rate, respiratory rate,
      oxygen saturation, blood ionised calcium concentration, serum total magnesium
      concentration, serum intact parathyroid hormone (PTH) level, and plasma EDTA
      level were assessed at periodic intervals during and following the bolus and
      continuous infusion of trial medication. Mean arterial pressure significantly
      decreased (p < 0.05) following the bolus injection of both trial medications and
      returned to baseline at 60 minutes; it significantly decreased again during the
      continuous infusion and returned to baseline during recovery. Heart rate and
      respiratory rate fluctuated in both groups with significant increases and
      decreases throughout the study period following the bolus injection; both
      returned to baseline during the recovery period in each group. Ionised calcium
      and total magnesium concentrations remained within normal limits and were
      unchanged in response to both study medications. PTH levels significantly
      increased following the bolus injection of both study drugs. The increase in PTH
      levels was greater with higher doses of study medication during the infusion
      period. There was no difference in the response of blood pressure, heart rate,
      respiratory rate, or PTH levels between propofol and propofol with EDTA. EDTA
      levels increased significantly during the infusion of propofol with EDTA,
      reaching mean levels of 240 ng/mL. CONCLUSIONS: The results of this study
      indicate that propofol increases PTH levels in normal subjects; however, propofol
      with EDTA does not alter ionised calcium or total magnesium concentrations.

PMID- 11310904
TI  - Trace element homeostasis during continuous sedation with propofol containing
      EDTA versus other sedatives in critically ill patients.
AB  - OBJECTIVE: To evaluate changes in serum and urinary zinc, cobalt, copper, iron,
      and calcium concentrations in critically ill patients receiving propofol
      containing disodium edetate (disodium ethylenediaminetetraacetic acid [EDTA])
      versus sedative agents without EDTA. DESIGN: This was a randomised, open-label,
      parallel-group study with randomisation stratified by baseline Acute Physiology
      and Chronic Health Evaluation (APACHE II) scores. SETTING: Intensive care units
      (ICU) in 23 medical centres. PATIENTS: Medical, surgical, or trauma ICU patients
      17 years of age or older who required mechanical ventilator support and sedation.
      INTERVENTIONS: A total of 106 patients received propofol containing 0.005 % EDTA
      (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA).
      Only the first 108 patients were assessed for urinary trace metal excretion.
      Twenty-four-hour urine samples were collected on days 2, 3, and 7 and every 7
      days thereafter for determination of zinc, cobalt, copper, iron, and calcium
      excretion; EDTA levels; urine osmolality; albumin levels; and glucose levels. The
      first 143 patients were assessed for serum concentration of zinc, cobalt, copper,
      iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and
      once during each 24-hour urine collection. MEASUREMENTS AND RESULTS: For the
      assessment of trace metals, patients receiving propofol EDTA demonstrated
      increased mean urinary excretion of zinc, copper, and iron compared with the
      normal range. All patients receiving sedatives demonstrated increased urinary
      excretion of zinc and copper above normal reference values. Compared with the non
      EDTA sedative group, the propofol EDTA group demonstrated increased urinary
      excretion of zinc and iron. Mean serum concentrations of zinc and total calcium
      were decreased in both patient groups. Serum zinc concentrations increased from
      baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA
      group. Renal function, measured by blood urea nitrogen, serum creatinine, and
      creatinine clearance, did not deteriorate during ICU sedation with either
      regimen. CONCLUSION: This study showed that critical illness is associated with
      increased urinary losses of zinc, copper, and iron. Propofol EDTA-treated
      patients had greater urinary losses of zinc and iron and lower serum zinc
      concentrations compared with the non-EDTA sedative group. No adverse events
      indicative of trace metal deficiency were observed in either group. The clinical
      significance of trace metal losses during critical illness is unclear and
      requires further study.

PMID- 11310905
TI  - Effects of propofol containing EDTA on mineral metabolism in medical ICU patients
      with pulmonary dysfunction.
AB  - OBJECTIVE: To determine whether the addition of disodium edetate (EDTA) to
      propofol significantly alters mineral metabolism, adverse events, and outcome in
      critically ill medical patients with acute pulmonary dysfunction. DESIGN:
      Multicentre, double-randomised, double-blind, comparative trial. SETTING: Medical
      intensive care units of 5 health centres. PATIENTS: A total of 85
      haemodynamically stable men and women aged 18-81 years who had pulmonary
      dysfunction or adult respiratory distress syndrome as a primary diagnosis or
      complication and who were expected to require at least 48 hours of sedation and
      mechanical ventilation. INTERVENTIONS: Patients were randomised to receive
      propofol with or without EDTA and then to 1 of 2 sedation levels: light (Modified
      Ramsay Sedation Scale [MRSS] score of 2 to 3) or deep (MRSS score of 4 to 5).
      Propofol was administered by continuous infusion at an initial rate of 5
      microg/kg per min and titrated as needed. MEASUREMENTS AND RESULTS: Approximately
      63 % of patients had a high severity of illness as indicated by an Acute
      Physiology and Chronic Health Evaluation II score > or = 19. As expected, these
      patients had a higher mortality rate but did not require a higher dose of
      propofol or propofol with EDTA. Extensive evaluation of cation homeostasis showed
      that ionised calcium and magnesium concentrations remained remarkably stable
      during treatment. Total calcium concentration was low as a result of
      hypoalbuminemia. Parathyroid hormone (PTH) concentration was elevated in both
      study groups at baseline, on day 4, and at the end of sedation. There were no
      significant differences in electrolyte levels and no progression to renal
      dysfunction. There were also no significant differences in haemodynamic or
      adverse-event profiles. Treatment-related adverse events occurred in 5 patients
      in each group; 4 of these (in 3 patients receiving propofol and 1 patient
      receiving propofol with EDTA) were considered serious. Because a large percentage
      of patients experienced a change in sedation level, no analyses were performed
      using sedation level. CONCLUSIONS: The addition of EDTA to propofol does not
      alter calcium and magnesium homeostasis in critically ill patients with acute
      pulmonary dysfunction. The reason for the elevation in PTH concentrations in such
      patients is not known.

PMID- 11310906
TI  - Cation metabolism during propofol sedation with and without EDTA in patients with
      impaired renal function.
AB  - OBJECTIVE: To compare the effects of propofol with and without disodium edetate
      (EDTA) on cation metabolism in intensive care unit (ICU) patients with renal
      insufficiency who received propofol or propofol plus EDTA (propofol EDTA) for
      sedation and mechanical ventilation. DESIGN: Double-blind, randomised,
      multicentre study. SETTING: Medical and surgical ICUs from 5 hospitals. PATIENTS:
      Thirty-nine ICU patients with acute and chronic renal impairment expected to
      require at least 24 hours of continuous sedation and respiratory failure
      necessitating mechanical ventilation. INTERVENTIONS: Propofol or propofol EDTA
      administered for sedation by continuous intravenous infusion. MEASUREMENTS AND
      RESULTS: The depth of sedation, as measured by the Modified Ramsay Sedation
      Scale, was similar in the 2 groups, when adjusted for dosing differences. The
      amount of propofol required to maintain adequate sedation was decreased in both
      groups compared to propofol requirements in ICU patients with normal renal
      function. EDTA levels were elevated at baseline in both groups. In the propofol
      EDTA group, the EDTA levels increased further by 20 % but decreased to below
      baseline EDTA levels at 48 hours after sedation. In the propofol group, EDTA
      levels decreased during sedation and remained below baseline levels at 48 hours
      after sedation. PATIENTS in both groups were hypocalcaemic and hyperphosphataemic
      at baseline with low levels of 1,25-dihydroxyvitamin D and elevated parathyroid
      hormone (PTH) levels. Other than a slight difference in ionised serum calcium
      levels at 4 h after the start of sedation, there were no significant differences
      observed in serum calcium levels between the two groups. There were no
      significant differences in 1,25-dihydroxyvitamin D or PTH levels over time
      between the two groups. There was no significant effect on renal function in
      either group. CONCLUSIONS: The results of this study suggest that adding EDTA to
      propofol does not adversely affect cation homeostasis or renal function when used
      for sedation of ICU patients with renal insufficiency. Although EDTA levels
      increased over time from baseline levels in patients with renal insufficiency who
      receive propofol EDTA, this increase does not appear to be clinically
      significant, and EDTA levels return to below baseline levels within 48 hours of
      discontinuing the propofol EDTA infusion. The efficacy of propofol with and
      without EDTA also appears comparable in these patients.

PMID- 11310907
TI  - Effect of propofol with and without EDTA on haemodynamics and calcium and
      magnesium homeostasis during and after cardiac surgery.
AB  - OBJECTIVE: To determine the effect of the addition of disodium edetate (EDTA) to
      propofol on haemodynamics, ionised calcium and magnesium serum concentrations,
      and adverse events during cardiac surgery. DESIGN: Double-blind, randomised,
      multicenter trial. SETTING: Operating room and intensive care unit of 5 academic
      health centres. PATIENTS: A total of 102 evaluable patients, aged 34 to 85 years,
      undergoing first-time, elective coronary artery bypass graft surgery.
      INTERVENTIONS: Comparison of propofol with EDTA and propofol without EDTA, each
      in conjunction with the opioid sufentanil, for intraoperative anaesthesia and
      postoperative sedation. MEASUREMENTS AND RESULTS: There were no significant
      differences at any time between the two formulations in any clinical chemistry
      measurements, including ionised calcium, ionised magnesium, total calcium,
      parathyroid hormone, blood urea nitrogen, creatinine, sodium, potassium, and
      phosphate. During bypass, the mean concentration of ionised calcium decreased to
      below the normal range, but the decrease was similar in both groups (propofol
      with EDTA, 0.98 +/- 0.07 mmol/L [N = 51]; propofol, 0.99 +/- 0.10 mmol/ L [N =
      51]; p = NS). Calcium concentration returned to normal after rewarming. Mean
      ionised magnesium concentrations remained within normal limits in both groups.
      Similarly, there were no clinically meaningful differences between treatments
      with respect to haemodynamic variables, efficacy variables, or incidence of
      adverse events. CONCLUSIONS: The inclusion of EDTA in the current formulation of
      propofol appears to have no significant effects on calcium and magnesium
      profiles, renal function, haemodynamic variables, or other indicators of safety
      and efficacy during intraoperative anaesthesia and postoperative sedation in
      patients undergoing cardiac surgery.

PMID- 11310908
TI  - Safety and efficacy of propofol with EDTA when used for sedation of surgical
      intensive care unit patients.
AB  - OBJECTIVE: To compare propofol with disodium edetate (EDTA) and propofol without
      EDTAwhen used for the sedation of critically ill surgical intensive care unit
      (ICU) patients. DESIGN: Prospective, randomised, multicentre trial. PATIENTS: A
      total of 122 surgical ICU patients who required intubation and mechanical
      ventilation. INTERVENTIONS: Patients were randomised to receive either propofol
      or propofol plus EDTA (propofol EDTA) by continuous infusion for sedation.
      MEASUREMENTS AND RESULTS: The addition of EDTA to propofol had no effect on
      calcium or magnesium homeostasis, renal function, haemodynamic function, or
      efficacy when used for the sedation of surgical patients in the ICU. The most
      common adverse events were hypotension, atrial fibrillation, and hypocalcaemia.
      In this trial, a greater number of serious adverse events and adverse events
      leading to withdrawal occurred in the propofol group relative to the propofol
      EDTA group. There was a significantly lower crude mortality rate at 7 and 28 days
      for the propofol EDTA group compared with the propofol group. There were no
      statistically significant differences between groups with respect to depth of
      sedation. CONCLUSION: The propofol EDTA formulation had no effect on calcium or
      magnesium homeostasis, renal function, or sedation efficacy compared with
      propofol alone when used for sedation in critically ill surgical ICU patients.
      There was a significant decrease in mortality in the propofol EDTA group compared
      with the propofol group. Further investigations are needed to validate this
      survival benefit and elucidate a possible mechanism.

PMID- 11310909
TI  - Application service providers: an alternative approach to PACS implementation.
AB  - Several impediments have delayed the adoption of filmless imaging by the majority
      of radiology practitioners. These factors include concerns for technology
      obsolescence, limited available capital, and lack of existing information
      technology (IT) infrastructure and experienced personnel. Application service
      providers (ASPs) have begun to emerge as an alternative approach to the more
      traditional acquisition of picture archiving and communication (PAC) systems.
      This approach offers the prospective PACS customer the opportunity to outsource
      hardware, software, and IT services to a vendor on a fee-per-use basis. The ideal
      candidates for such an approach would be small to medium-sized hospitals with
      limited existing IT infrastructure. Using the ASP model, prospective PACS
      customers can purchase services unique to their needs and upgrade or expand these
      as needed. As ASP vendors increase their customer base, there is the potential
      for customers to achieve unique economies of scale not available through
      traditional financing means. This report discusses the economic and operational
      issues associated with ASPs, as well as potential limitations and future
      implications of this phenomenon.

PMID- 11310910
TI  - Digital processing of radiographic images from PACS to publishing.
AB  - Several studies have addressed the implications of filmless radiologic imaging on
      telemedicine, diagnostic ability, and electronic teaching files. However, many
      publishers still require authors to submit hard-copy images for publication of
      articles and textbooks. This study compares the quality digital images directly
      exported from picture archive and communications systems (PACS) to images
      digitized from radiographic film. The authors evaluated the quality of
      publication-grade glossy photographs produced from digital radiographic images
      using 3 different methods: (1) film images digitized using a desktop scanner and
      then printed, (2) digital images obtained directly from PACS then printed, and
      (3) digital images obtained from PACS and processed to improve sharpness prior to
      printing. Twenty images were printed using each of the 3 different methods and
      rated for quality by 7 radiologists. The results were analyzed for statistically
      significant differences among the image sets. Subjective evaluations of the
      filmless images found them to be of equal or better quality than the digitized
      images. Direct electronic transfer of PACS images reduces the number of steps
      involved in creating publication-quality images as well as providing the means to
      produce high-quality radiographic images in a digital environment.

PMID- 11310911
TI  - A hierarchical storage management (HSM) scheme for cost-effective on-line
      archival using lossy compression.
AB  - A hierarchical storage management (HSM) scheme for cost-effective on-line
      archival of image data using lossy compression is described. This HSM scheme also
      provides an off-site tape backup mechanism and disaster recovery. The full
      resolution image data are viewed originally for primary diagnosis, then
      losslessly compressed and sent off site to a tape backup archive. In addition,
      the original data are wavelet lossy compressed (at approximately 25:1 for
      computed radiography, 10:1 for computed tomography, and 5:1 for magnetic
      resonance) and stored on a large RAID device for maximum cost-effective, on-line
      storage and immediate retrieval of images for review and comparison. This HSM
      scheme provides a solution to 4 problems in image archiving, namely cost
      effective on-line storage, disaster recovery of data, off-site tape backup for
      the legal record, and maximum intermediate storage and retrieval through the use
      of on-site lossy compression.

PMID- 11310912
TI  - Comparison of radiographic image quality from four digitization devices as viewed
      on computer monitors.
AB  - The objective of this study was to compare the quality of radiographic images
      digitized from commercial-grade and consumer-grade digital cameras and scanners
      as viewed on computer monitor. Radiographic images were digitized from hardcopy
      film using a commercial-grade laser scanner, a consumer-grade desktop flatbed
      scanner, a commercial-grade digital camera, and a consumer-grade digital camera.
      The quality of images without and with grayscale histogram adjustment was
      evaluated subjectively by 10 board-certified radiologists. Optical density
      response was evaluated objectively using a grayscale test pattern. There was no
      significant difference in subjective quality among images digitized with the
      commercial scanner, consumer scanner, and commercial camera. The quality of
      images digitized with the consumer camera was lower than the other 3. Objective
      tests showed the commercial scanner to have the most linear optical density
      response. For the purpose of viewing images on a computer monitor, a consumer
      grade desktop scanner can produce images of similar quality to those produced by
      more expensive laser commercial-grade scanners and digital cameras and provides
      cost-efficient means to digitize radiographic plain films. A consumer-grade
      camera may not be optimal for use in this setting.

PMID- 11310913
TI  - Initial evaluation of a continuous speech recognition program for radiology.
AB  - The aims of this work were to measure the accuracy of one continuous speech
      recognition product and dependence on the speaker's gender and status as a native
      or nonnative English speaker, and evaluate the product's potential for routine
      use in transcribing radiology reports. IBM MedSpeak/Radiology software, version
      1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were
      men. Each speaker dictated a set of 12 reports. The reports included neurologic
      and body imaging examinations performed with 6 different modalities. The dictated
      and original report texts were compared, and error rates for overall,
      significant, and subtle significant errors were computed. Error rate dependence
      on modality, native English speaker status, and gender were evaluated by
      performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in
      accuracy between men and women was found; however, significant differences were
      seen for overall and significant errors when comparing native and nonnative
      English speakers (P = .009 and P = .008, respectively). The speech recognition
      software is approximately 90% accurate, and while practical implementation issues
      (rather than accuracy) currently limit routine use of this product throughout a
      radiology practice, application in niche areas such as the emergency room
      currently is being pursued. This methodology provides a convenient way to compare
      the initial accuracy of different speech recognition products, and changes in
      accuracy over time, in a detailed and sensitive manner.

PMID- 11310914
TI  - Tissue segmentation-assisted analysis of fMRI for human motor response: an
      approach combining artificial neural network and fuzzy C means.
AB  - The authors have developed an automated algorithm for segmentation of magnetic
      resonance images (MRI) of the human brain. They investigated the quantitative
      analysis of tissue-specific human motor response through an approach combining
      gradient echo functional MRI and automated segmentation analysis. Fifteen healthy
      volunteers, placed in a 1.5 T clinical MR imager, performed a self-paced finger
      opposition throughout the activation periods. T1-weighted images (WI), T2WI, and
      proton density WI were acquired for segmentation analysis. Single-slice axial T2*
      fast low-angle shot (FLASH) images were obtained during the functional study.
      Pixelwise cross-correlation analysis was performed to obtain an activation map. A
      cascaded algorithm, combining Kohonen feature maps and fuzzy C means, was applied
      for segmentation. After processing, masks for gray matter, white matter, small
      vessels, and large vessels were generated. Tissue-specific analysis showed a
      signal change rate of 4.53% in gray matter, 2.98% in white matter, 5.79% in small
      vessels, and 7.24% in large vessels. Different temporal patterns as well as
      different levels of activation were identified in the functional response from
      various types of tissue. High correlation exists between cortical gray matter and
      subcortical white matter (r = 0.957), while the vessel behaves somewhat different
      temporally. The cortical gray matter fits best to the assumed input function (r =
      0.957) followed by subcortical white matter (r = 0.829) and vessels (r = 0.726).
      The automated algorithm of tissue-specific analysis thus can assist functional
      MRI studies with different modalities of response in different brain regions.

PMID- 11310915
TI  - Implementing a Java-based image and report distribution system in a non-picture
      archiving and communication environment.

PMID- 11310916
TI  - Adobe acrobat: an alternative electronic teaching file construction methodology
      independent of HTML restrictions.
AB  - The goal of the project was to create a method by which an in-house digital
      teaching file could be constructed that was simple, inexpensive, independent of
      hypertext markup language (HTML) restrictions, and appears identical on multiple
      platforms. To accomplish this, Microsoft PowerPoint and Adobe Acrobat were used
      in succession to assemble digital teaching files in the Acrobat portable document
      file format. They were then verified to appear identically on computers running
      Windows, Macintosh Operating Systems (OS), and the Silicon Graphics Unix-based OS
      as either a free-standing file using Acrobat Reader software or from within a
      browser window using the Acrobat browser plug-in. This latter display method
      yields a file viewed through a browser window, yet remains independent of
      underlying HTML restrictions, which may confer an advantage over simple HTML
      teaching file construction. Thus, a hybrid of HTML-distributed Adobe Acrobat
      generated WWW documents may be a viable alternative for digital teaching file
      construction and distribution.

PMID- 11310917
TI  - DNA topoisomerase IIalpha protein and mRNA expression in intracranial
      meningiomas.
AB  - We examined the expression of DNA topoisomerase IIalpha (Topo IIalpha)
      immunohistochemically using a monoclonal antibody and compared its proliferative
      potential [MIB-1 labeling index (LI)] and recurrence to verify the possible
      influence of Topo IIalpha on the progress of meningiomas. The reverse
      transcription-polymerase chain reaction (RT-PCR) assay was also performed to
      evaluate the expression of Topo IIalpha mRNA. Formalin-fixed, paraffin-embedded
      tissue sections of 52 meningiomas (18 meningothelial types, 16 fibrous types, 4
      transitional types, 4 psammomatous types, 1 angiomatous type, 1 secretory type, 5
      atypical types, and 3 anaplastic types) were used for immunostaining. The Topo
      IIalpha labeling index (LI) was 1.4 +/- 1.9% (mean +/- SE) in benign meningiomas
      and 4.5 +/- 1.6% in atypical or anaplastic meningiomas, representing significant
      differences between them (P < 0.0001). RT-PCR assay revealed that Topo IIalpha
      mRNA expression was associated with Topo IIalpha LI. A significant correlation
      was seen between Topo IIalpha LI and MIB-1 LI (r = 0.517; P < 0.01). Recurrence
      was significantly more frequent in patients with more than 1.5% of Topo IIalpha
      LI than in those with 1.5% or less (P < 0.005). In conclusion, Topo IIalpha
      protein and mRNA expression correlated with clinical malignancy and the potential
      for predicting the regrowth of meningiomas.

PMID- 11310918
TI  - Clinicopathological study of vascular endothelial growth factor (VEGF), p53, and
      proliferative potential in familial von Hippel-Lindau disease and sporadic
      hemangioblastomas.
AB  - We examined the clinical characteristics and prognosis in six patients with
      familial von Hippel-Lindau (VHL) disease and seven with sporadic
      hemangioblastomas. The expression of vascular endothelial growth factor (VEGF),
      p53 protein, and proliferative potential with Ki67 monoclonal antibody (MIB-1)
      was compared using immunohistochemical methods between sporadic and VHL disease
      associated hemangioblastomas. Patients with sporadic CNS hemangioblastomas were
      treated by total removal of the tumors, and they had a good long-term prognosis
      without neurological deficits on recurrence. However, patients with familial VHL
      disease often had multiple hemangioblastomas in the CNS and visceral tumors. Even
      if total removal of CNS hemangioblastomas in patients with VHL disease was
      performed initially, small multiple hemangioblastomas recurred during long-term
      follow-up in areas remote from the primary region resected by surgery. All of the
      hemangioblastomas displayed extensive overexpression of VEGF protein, with
      moderate to marked proliferation of blood vessels. The MIB-1 indices showed low
      values of 0.8% as the mean, with a range of 0.03%-2.1% for all the
      hemangioblastomas. None of the hemangioblastomas expressed p53 protein. The
      hemangioblastomas in patients with VHL disease were multiple in the CNS and were
      combined with visceral tumors. Patients with VHL disease had a poor long-term
      prognosis, in contrast to those with sporadic hemangioblastomas. The
      immunohistochemical findings for VEGF protein, p53 protein, and MIB-1 did not
      differ significantly between the sporadic and VHL disease-associated
      hemangioblastomas.

PMID- 11310919
TI  - Vascular abnormalities in surgical specimens obtained from the resected focus of
      intractable epilepsy.
AB  - The histopathological features, particularly hypervascularity, were examined in
      specimens resected from 21 patients, 15 with intractable epilepsy accompanying
      cortical dysplasia or dysembryoplastic neuroepithelial tumor (DNT), and 6 with
      benign brain tumors, such as ganglioglioma and low-grade glioma. Hypervascularity
      was found in resected specimens from 15 of the 21 patients (71.4%) and in 10 of
      the 12 patients (83.3%) who had double pathology. Counting of numbers of vessels
      by CD31 immunohistochemistry revealed that hypervascularity was prominent,
      especially in cases of vascular malformation or cortical dysplasia. However,
      almost all cases were negative for vascular endothelial growth factor (VEGF)
      staining, except for some cases of benign brain tumors. Moreover, all cases
      showed low or no proliferative potential in MIB-1 immunohistochemistry. These
      results suggest that the etiology of hypervascularity in the dysplastic lesions
      is one of a variety of cerebral malformations, as is the case with abnormal
      maturation and differentiation in neuroglial elements.

PMID- 11310920
TI  - Histopathological and physiological characteristics of cultured human ACTH
      secreting cells derived from a rapidly growing pituitary adenoma.
AB  - We observed the histopathological and physiological characteristics of
      adrenocorticotropic hormone (ACTH)-secreting adenoma cells derived from a rapidly
      growing pituitary adenoma, which have firm cell attachment and well-preserved
      hormonal function in a relatively longterm culture. Corticotrophs, obtained from
      a 43-year-old woman with Cushing's disease in whom plasma ACTH levels increased
      in response to 1-deamino-8-D-arginine vasopressin (DDAVP) stimulation and the
      proliferative potential was very high, were grown in tissue culture for up to 6
      months. The morphological features were observed by phase contrast and electron
      microscopy. The cultured cells were incubated with corticotroph-releasing hormone
      (CRH), arginine vasopressin (AVP), or DDAVP, and ACTH in the medium was measured
      by radioimmunoassay (RIA). The morphology of the ACTH-secreting adenoma cells in
      culture revealed a mixed population of formed clusters and spindle-shaped
      fibroblast-like cells. The adenoma cells were immunohistochemically positive only
      for ACTH. On electron microscopic observation, pituitary tumor cells obtained 6
      days after seeding demonstrated many secretory granules, well-developed rough
      endoplasmic reticulum, and mitochondria; fewer secretory granules were observed
      after cultivation for 24 days. ACTH levels in the incubation media were elevated
      with stimulation by DDAVP, AVP, or CRH. In this study, the establishment of
      relatively longterm culture of human pituitary adenoma cells seemed to be due to
      the high proliferative potential of this adenoma. This in vitro study may imply
      that DDAVP as well as AVP directly stimulates ACTH release from corticotropic
      adenoma cells.

PMID- 11310921
TI  - Brain necrosis after permanent low-activity iodine-125 implants: case report and
      review of toxicity from focal radiation.
AB  - Focal irradiation has emerged as a useful modality in the management of malignant
      brain tumors. Its main limitation is radiation necrosis. We report on the
      radiation dose distribution in the cerebellum of a patient who developed imaging
      and autopsy diagnosis of radiation necrosis after permanent iodine-125 implants
      for a solitary osseous plasmacytoma of her left occipital condyle. A 55-year-old
      woman initially presented with neck and occipital pain and a lytic lesion of her
      left occipital condyle. A cytological diagnosis of solitary osseous plasmacytoma
      was made by transpharyngeal needle biopsy. After an initial course of external
      beam radiation, the patient required further treatment with systemic chemotherapy
      21 months later for clinical and radiographic progression of her disease. She
      ultimately required subtotal surgical resection of an anaplastic plasmacytoma
      with intracranial extension. Permanent low-activity iodine-125 seeds were
      implanted in the tumor cavity. Satisfactory local control was achieved. However,
      clinical and imaging signs of radiation damage appeared 28 months after iodine
      125 seed implantation. Progressive systemic myeloma led to her death 11 years
      after presentation and 9 years after seed implantation. Radiation dose
      distribution is described, with a discussion of toxicity from focal radiation
      dose escalation.

PMID- 11310922
TI  - Pilocytic astrocytoma arising from an area of nodular heterotopia located in the
      white matter of the temporal lobe: case report.
AB  - A 16-year-old girl suffering from intractable temporal lobe epilepsy presented
      with a pilocytic astrocytoma, which occurred in an area of nodular heterotopia
      located in the white matter of the temporal lobe. The pilocytic astrocytoma
      appeared to be covered by an area of gliosis, which contained numerous Rosenthal
      fibers, while in the lesion the pilocytic astrocytoma occupied a small area. The
      gliosis eventually became a tumor-like lesion. The white matter around the mass
      was composed of gliosis with nodular heterotopia. Temporal developmental
      malformation, which was a basic lesion of the patient, might therefore be a
      precursor lesion of pilocytic astrocytomas.

PMID- 11310923
TI  - Chordoid meningioma.
AB  - Chordoid meningioma is a relatively rare variant that is often associated with
      peritumoral lymphoplasmacellular infiltration causing Castleman syndrome (CS). We
      present a 44-year-old woman with chordoid meningioma not associated with CS. The
      patient presented with epilepsy and right hemiparesis (Todd's palsy) on
      admission. The radiological findings revealed an extraaxial mass lesion in the
      premotor cortex. They were compatible with a preoperative diagnosis of
      meningioma. No physical abnormalities related to CS were detected. A left frontal
      craniotomy was performed. The tumor surface was gelatinous, and it was totally
      resected with the attached dura mater (Simpson grade I). The patient had an
      uneventful recovery, and her seizures subsided. The pathological findings of the
      specimens revealed nests and cords of spindle and epithelioid cells with abundant
      myxoid matrix, mimicking the features of chordoma. On the basis of radiological,
      immunohistochemical, and electron microscopic findings, chordoid meningioma was
      verified, and a review of the literature was performed.

PMID- 11310924
TI  - High-grade adenoid cystic carcinoma originating from the lacrimal gland.
AB  - Among primary lacrimal gland tumors, adenoid cystic carcinoma (ACC) is the most
      common malignant epithelial neoplasm; it is characterized by local intracranial
      invasion. A case with unusual dumbbell-type intracranial extension representing
      cavernous sinus syndrome is described. A 49-year-old woman was admitted to our
      hospital with right cavernous sinus syndrome. Computerized tomographic (CT) scans
      and magnetic resonance (MR) imaging demonstrated well-enhanced intraorbital and
      middle fossa tumors mimicking multifocal mass lesions. Operative findings
      revealed an ACC originating from the lacrimal gland and extending into the right
      cavernous sinus and middle fossa along the nerve sheath in the superior orbital
      fissure. Although MR image findings of intracranial ACC often resemble the image
      findings for meningiomas, intracranial ACC is very aggressive in comparison with
      meningioma. It is best treated surgically and aggressively.

PMID- 11310925
TI  - Intracranial plasma cell granuloma.
AB  - Plasma cell granulomas (PCGs) are benign, inflammatory masses of unknown etiology
      composed of polyclonal mature plasma and lymphoid cells. The lung is their most
      common location, and occurrence within the cranial cavity is extremely rare. We
      report the case of an 11-year-old girl who presented with seizures and was
      diagnosed as having a dural-based right frontal tumor that extended toward the
      sagittal sinus and the falx. The lesion was totally excised, together with the
      abnormal dura. A limited cortical excision was also performed using
      electrocorticographic guidance. Histopathologic diagnosis of intracranial plasma
      cell granuloma was reached after extensive immunohistochemical tests and electron
      microscopy. This is the third case of PCG with description of changes in the
      neighboring cerebral tissue. Although PCGs are well-circumscribed lesions,
      lymphoplasmocytic inflammation, neuronal loss, and reactive gliosis occur within
      the adjacent cortex. Disturbed cortical lamination, as we have observed, appears
      to be a histological finding that has not been described previously.

PMID- 11310926
TI  - Plasma lactate, GH and GH-binding protein levels in exercise following BCAA
      supplementation in athletes.
AB  - Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone
      (GH) is a mediator in this process. A pre-exercise BCAA ingestion increases
      muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment
      (0.2 gkg(-1) of body weight), the effects of a pre-exercise oral supplementation
      of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before
      and after 60 min of physical exercise (75% of VO2 max). The plasma levels of GH
      (pGH) and of growth hormone binding protein (pGHBP) were also studied. The end
      exercise La of each athlete was higher than basal. Furthermore, after the chronic
      BCAA treatment, these end-exercise levels were lower than before this treatment
      (8.6+/-0.8 mmol L(-1) after vs 12.8+/-1.0 mmol L(-1) before treatment; p < 0.05
      [mean +/- std. err.]). The end-exercise pGH of each athlete was higher than basal
      (p < 0.05). Furthermore, after the chronic treatment, this end-exercise pGH was
      higher (but not significantly, p = 0.08) than before this treatment (12.2+/-2.0
      ng mL(-1) before vs 33.8+/-13.6 ngmL(-1) after treatment). The end-exercise pGHBP
      was higher than basal (p < 0.05); and after the BCAA chronic treatment, this end
      exercise pGHBP was 738+/-85 pmol L(-1) before vs 1691+/-555 pmol L(-1) after.
      pGH/pGHBP ratio was unchanged in each athlete and between the groups, but a
      tendency to increase was observed at end-exercise. The lower La at the end of an
      intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA
      chronic treatment. The chronic BCAA effects on pGH and pGHBP might suggest an
      improvement of muscle activity through protein synthesis.

PMID- 11310927
TI  - Changes in plasma and urinary taurine and amino acids in runners immediately and
      24h after a marathon.
AB  - Changes in urinary and plasma taurine and amino acids have been evaluated in
      trained runners competing in the Rotterdam Marathon, 1998, both immediately after
      completing the event and 24h after recovery. There were significant changes in
      the urinary amino acids excretion, the majority showing a significant decrease
      both immediately at the completion of the Marathon and after 24h recovery. In
      contrast urinary taurine excretion increased immediately post Marathon, although
      not significantly as the range of results was wide. Such changes in urinary
      taurine correlated with percentage changes in plasma creatine kinase both
      immediately post race, (r = 0.972, P < 0.001), and 24h later (r = 0.872, P <
      0.001), possibly indicating that the source of the taurine was muscle.
      Significant correlations between the individual values for urinary and plasma
      amino acids in all of the athletes were calculated for taurine (r = 0.528),
      glycine (r = 0.853), threonine (r = 0.749), alanine (r = 0.747), serine (r =
      0.620), glutamine (0.614), arginine (r = 0.507), histidine (r = 0.470) and valine
      (r = 0.486). Changes in the mean plasma concentrations of amino acids were
      comparable to our previously published data (Ward et al., 1999) the majority
      showing significant decreases immediately and 24h post Marathon, such an
      adaptation being due primarily to their utilisation for gluconeogenesis. However,
      in contrast, the mean taurine concentrations were significantly elevated both
      post race, P < 0.01 and after 24h, P < 0.05. The physiological response by the
      muscle to exhaustive exercise, particularly with regard to changes in plasma and
      urinary taurine concentrations remain to be elucidated, but is probably related
      to muscle function impairment. The increase in taurine urinary excretion could be
      used as an indicator of muscle damage occurring during exhaustive exercise.
      Whether taurine supplementation would minimise such changes is an interesting
      scientific question and merits investigation.

PMID- 11310928
TI  - Amino acids and central fatigue.
AB  - There is an increasing interest in the mechanisms behind central fatigue,
      particularly in relation to changes in brain monoamine metabolism and the
      influence of specific amino acids on fatigue. Several studies in experimental
      animals have shown that physical exercise increases the synthesis and metabolism
      of brain 5-hydroxytryptamine (5-HT). Support for the involvement of 5-HT in
      fatigue can be found in studies where the brain concentration of 5-HT has been
      altered by means of pharmacological agents. When the 5-HT level was elevated in
      this way the performance was impaired in both rats and human subjects, and in
      accordance with this a decrease in the 5-HT level caused an improvement in
      running performance in rats. The precursor of 5-HT is the amino acid tryptophan
      and the synthesis of 5-HT in the brain is thought to be regulated by the blood
      supply of free tryptophan in relation to other large neutral amino acids
      (including the branched-chain amino acids, BCAA) since these compete with
      tryptophan for transport into the brain. Studies in human subjects have shown
      that the plasma ratio of free tryptophan/BCAA increases during and, particularly,
      after sustained exercise. This would favour the transport of tryptophan into the
      brain and also the synthesis and release of 5-HT which may lead to central
      fatigue. Attempts have been made to influence the 5-HT level by giving BCAA to
      human subjects during different types of sustained heavy exercise. The results
      indicate that ingestion of BCAA reduces the perceived exertion and mental fatigue
      during exercise and improves cognitive performance after the exercise. In
      addition, in some situations ingestion of BCAA might also improve physical
      performance; during exercise in the heat or in a competitive race when the
      central component of fatigue is assumed to be more pronounced than in a
      laboratory experiment. However, more experiments are needed to further clarify
      the effect of BCAA and also of tryptophan ingestion on physical performance and
      mental fatigue.

PMID- 11310929
TI  - Influence of exercise on serotonergic neuromodulation in the brain.
AB  - Implications of exercise on serotonergic neuromodulation in the brain have been
      investigated in two studies. Acute paroxetine (selective serotonin (5-HT)
      reuptake inhibitor) administration to endurance athletes, who performed a cycle
      ergometer test to exhaustion at moderate intensity, reduced time to exhaustion
      and post exercise cognitive performance in comparison to trials with placebo or
      BCAA administration. Furthermore, during a 3-week moderate endurance training of
      sedentary males basaline values of Bmax of 5-HT transporters (5-HTT) and 5-HT2A
      receptors (5-HT(2A)R) on isolated platelet membranes increased while plasma
      prolactin (PRL) concentrations decreased as well as mood and physical efficiency
      improved. In contrast, after an excessive training program over four weeks, well
      trained endurance athletes showed no change of Bmax of 5-HTT, but a decline of 5
      HT(2A)R density and an increase in basal plasma PRL concentration. Mood was
      impaired and central fatigue increased. Thus, the impact of exercise on 5-HT
      neurotransmission may depend on training state of athletes and extent of
      exertion. The theoretical background of the implication of exercise and the
      effect of long lasting exhaustive exercise in athletes on mental and physical
      efficiency or central fatigue are evaluated. The significance of the primary
      disturbance of central neuromodulation and dysfunction of 5-HTT, 5-HT receptor
      subtypes and the phosphoinositol signal transduction as well as the limited
      modulation capacity of the 5-HT system in overstrain are also addressed.

PMID- 11310930
TI  - The relation between glutamine and the immunodepression observed in exercise.
AB  - Glutamine is the most abundant amino acid in the body. It is an important fuel
      for some key cells of the immune system. Both the plasma concentration of
      glutamine and the functional ability of immune cells in the blood are decreased
      after prolonged, exhaustive exercise. Glutamine feeding has had beneficial
      effects in clinical situations, and the provision of glutamine after intensive
      exercise has decreased the incidence of infections, particularly of upper
      respiratory tract infections. However, the precise effect of glutamine on
      immunodepression in this situation is not yet established.

PMID- 11310931
TI  - Readiness potential in different states of physical activation and after
      ingestion of taurine and/or caffeine containing drinks.
AB  - To investigate the influence of taurine and caffeine containing drinks and
      physical stress on the cortical movement-preparation, the readiness potentials or
      "Bereitschaftspotentiale" (BPs), preceding voluntary self-placed pedalling
      movements, were examined after different states of exhaustion on an ergometer. 15
      (13 right-handed) healthy men, aged between 22-30, participated in a randomised,
      cross over, double-blind, placebo controlled study. BPs were averaged out of
      artefact free EEG-segments from more than 90 triggered events, measured at 17
      electrodes of the 10:20 system. With increasing effort the BPs were enlarged
      differently depending on the drink consumed. In placebo trials after exhaustive
      exercise premovement negative potential curves could be seen even in frontal
      areas. With caffeine the BPs increased after lower workload, achieving a level,
      which was reached in the placebo trials only after submaximal physical
      activation. Furthermore a significant shortening of premovement-brain-potentials
      in frontal and parietal regions could be seen in the caffeine trials at rest.
      Taurine admixture seems to inhibit this effects.

PMID- 11310932
TI  - The influence of a taurine containing drink on cardiac parameters before and
      after exercise measured by echocardiography.
AB  - To determine the effect of the taurine containing drink "Red Bull" on cardiac
      parameters thirteen endurance trained subjects performed an exhaustive bout of
      endurance exercise at three different times. Prior to the exercise the original
      "Red Bull" drink, a similar drink without taurine, containing caffeine, and a
      "placebo" drink without caffeine and without taurine were ingested by the
      subjects in a double-blind cross-over design. Echocardiographic examinations were
      performed before the drinks, 40 minutes after the drinks prior to the exercise
      and in the regeneration period after exercise. Stroke volume was significantly
      influenced only in the "Red Bull group" (80,4+/-21,4 ml before drink vs. 97,5+/
      26,2 ml in the regeneration period), mainly due to a reduced endsystolic diameter
      and volume. Furthermore in this group the peak late diastolic inflow (V(A)) in
      the regeneration period was significantly higher compared with the pre-exercise
      levels. This observation was also made in the caffeine group but without any
      consequences on ventricular function. The results of the present study show an
      influence of the original caffeine and taurine containing drink (Red Bull) on
      parameters of the cardiac contractility.

PMID- 11310933
TI  - Beneficial effects of an "energy drink" given to sleepy drivers.
AB  - 500 ml of a glucose based "energy" drink versus a control without the active
      ingredients (caffeine, taurine, glucuronolactone) were given double blind to 11
      sleepy participants driving an interactive real-car driving simulator. Lane
      drifting and a secondary task (reaction time) were measured for two hours post
      treatment. The energy drink significantly improved both indices, particularly for
      the first hour.

PMID- 11310934
TI  - Otitis media with effusion: the role of Alloiococcus otitidis.
AB  - Otitis media with effusion (OME) is a common condition that can cause deafness as
      well as speech and behavioural disturbance. It has long been considered to be a
      noninfective process resulting from Eustachian tube dysfunction; however,
      molecular biological techniques have implicated bacteria in the aetiology of this
      condition. One such organism is Alloiococcus otitidis, which has been detected in
      middle ear fluid of patients with OME which has not yielded micro-organisms with
      conventional microbiological culture methods. The exact role of this infectious
      agent in the pathogenesis of otitis media has yet to be elucidated.

PMID- 11310935
TI  - Tissue-specific insulin resistance in type 2 diabetes: lessons from gene-targeted
      mice.
AB  - Type 2 diabetes is caused by genetic and environmental factors that affect the
      ability of the organism to respond to insulin. This impairment results from
      decreased insulin action in target tissues and insulin production in beta cells.
      Genetic factors play a key role in the development of type 2 diabetes. However,
      the inheritance of diabetes is non-Mendelian in nature because of genetic
      heterogeneity, polygenic pathogenesis, and incomplete penetrance. Novel insight
      into this complex process has been obtained from 'designer' mice bearing targeted
      mutations in genes of the insulin action and insulin secretion pathways. These
      mutant mice are beginning to challenge established paradigms in the pathogenesis
      of type 2 diabetes and to shed light on the genetic interactions underlying its
      complex inheritance. Here we review recent progress in the field and assess its
      relevance to the pathogenesis of diabetes in humans.

PMID- 11310936
TI  - From gene transfer to gene therapy in lysosomal storage diseases affecting the
      central nervous system.
AB  - Gene transfer into the central nervous system (CNS) is one of the foremost
      scientific challenges today. To give a brief survey of possible approaches to
      gene therapy in diseases affecting the CNS, we have selected the lysosomal
      storage diseases (LDS), which are an excellent model of both early-onset
      infantile neurological forms and late-onset adult psychiatric forms. Lysosomal
      storage diseases represent a group of about 50 monogenic metabolic disorders
      resulting from a deficiency in intralysosomal enzymes involved in macromolecule
      catabolism. The clinical severity, including neuropsychiatric symptoms, and the
      absence of an efficient therapy for the majority of these disorders prompted the
      various trials of gene therapy now in progress. Most of the genes encoding the
      normal lysosomal enzymes have been cloned, and the size of the corresponding
      cDNAs is generally compatible with their transfer by recombinant vectors. New
      vectors with improved immunogenicity, transduction efficacy, insert capacity, and
      specificity of targeting are under development. Here we discuss several gene
      therapy strategies for the correction of LSD-induced anomalies in the CNS.
      Interesting results have been obtained by animal model brain, which raises hopes
      that large-scale clinical trials may soon be started.

PMID- 11310937
TI  - C-reactive protein, fibrinogen, interleukin-6 and tumour necrosis factor-alpha in
      the prognostic classification of unstable angina pectoris.
AB  - BACKGROUND: Inflammatory process has been found to play an important role in the
      pathogenesis of coronary heart disease (CHD) and in the prognosis of CHD
      patients. AIM. The aim of this study was to investigate the prognostic value of C
      reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor
      alpha (TNF-alpha) in patients with unstable angina pectoris (UAP), including
      factor analysis to assess their joint effects. METHODS: The study comprised 263
      consecutive patients (159 men, 104 women; median age 68 years) with UAP. Blood
      samples for the acute-phase protein and cytokine determinations were drawn on
      admission. RESULTS: Coronary mortality during the median follow-up time of 17
      months was 6-fold higher in the highest tertile for CRP and IL-6 and 3.5-fold
      higher in the highest tertile for fibrinogen and TNF-alpha than in the respective
      combined lower tertiles. Factor analysis produced two underlying factors, ie the
      'inflammation' factor, including CRP, fibrinogen and IL-6, and the 'injury'
      factor, including troponin T, creatine kinase MB mass and TNF-alpha. In Cox
      models, both of these factors were independent predictors of the risk of coronary
      death and major coronary events (coronary death or nonfatal myocardial
      infarction). CONCLUSIONS: Elevated levels of acute-phase proteins and cytokines,
      particularly CRP and IL-6, are strong predictors of the risk of serious coronary
      events in patients with UAP.

PMID- 11310938
TI  - Managing the menopause: phyto-oestrogens or hormone replacement therapy?
AB  - Menopause is a natural event, and understandably many women would like to take a
      natural therapy rather than a drug for managing their menopause symptoms as well
      as preventing the long-term sequelae of oestrogen deficiency. In this respect
      phyto-oestrogens show a lot of promise. However, at this point in time clinical
      data are inconclusive. There are some data supporting the contention that
      isoflavones improve hot flushes; however, there are also negative studies. Soy
      protein has been shown to lower cholesterol, and isoflavones improve arterial
      compliance. Clinical studies suggest that isoflavones have little impact on
      menopause-induced bone loss.

PMID- 11310939
TI  - Screening of plasma homocysteine in peripheral arterial disease.
AB  - BACKGROUND: Homocysteine (HCY) was recently established as an independent risk
      factor for atherosclerosis. The prevalence of an increased homocysteine plasma
      concentration was reported to be up to 6-fold higher in patients with different
      locations of arterial occlusive diseases. AIM: This study evaluated critically
      whether the total HCY plasma concentration can be used as a screening marker for
      peripheral arterial disease in the general population. METHODS: Study subjects
      were 40 patients (51.8 +/- 7.5 years) with symptomatic lower limb peripheral
      arterial disease (PAD) (stage II) and 40 healthy volunteers (45.6 +/- 6.8 years,
      P< 0.05 vs PAD). The percentage of women in both groups was 30%. The plasma HCY
      concentration was determined by using derivatization techniques and subsequent
      fluorescence high-performance liquid chromatography. RESULTS: Total plasma HCY
      concentration was significantly higher in the PAD group than in controls (14.90
      +/- 5.78 microM vs 11.32 +/- 2.95 microM, respectively, P< 0.001). Also, the
      coefficient of variation of plasma HCY in PAD was significantly higher than that
      in the control group, 0.38 vs 0.25 (P< 0.001), respectively, reflecting greater
      interindividual differences. In addition to a PAD-specific effect, the plasma HCY
      concentration was also dependent on gender and age (both P< 0.05). Sensitivity
      and specificity of HCY as a marker of PAD were 0.3 and 0.95, respectively.
      Positive and negative predictive values were 0.85 and 0.42, respectively.
      CONCLUSIONS: From these data it is concluded that HCY metabolism may have an
      influence on the development of PAD in one-third of all patients with PAD, and
      that total plasma HCY concentration may not be suited as a screening test for PAD
      in the general population but rather serves as a monitoring marker in certain
      risk groups.

PMID- 11310940
TI  - LCx Mycobacterium tuberculosis assay is valuable with respiratory specimens, but
      provides little help in the diagnosis of extrapulmonary tuberculosis.
AB  - BACKGROUND: Commercial nucleic acid amplification tests, designed for the
      detection of Mycobacterium tuberculosis DNA/RNA in respiratory samples, are often
      applied also in nonrespiratory specimens in order to verify the diagnosis of
      extrapulmonary tuberculosis. AIM. To evaluate the value of the Abbott LCx
      Mycobacterium tuberculosis assay for the diagnosis of pulmonary and
      extrapulmonary tuberculosis based on routine clinical laboratory results.
      METHODS: The assay was used to analyse 350 respiratory and 826 nonrespiratory
      specimens from 961 patients, of whom 3.6% had culture-proven tuberculosis. The
      results obtained by the LCx assay were compared with the records on mycobacterial
      isolates of the national reference laboratory and, in the case of positive
      findings, with clinical data. RESULTS: In comparison with culture, the
      sensitivity, specificity and positive/negative predictive value of the assay on
      respiratory specimens were 87.5%, 99.7%, 93.3% and 99.4%, respectively. With
      nonrespiratory specimens, the overall sensitivity, specificity and
      positive/negative predictive value of the LCx assay were 73.3%, 98.0%, 40.7% and
      99.5%, respectively. When clinical and histological data were also included, the
      positive predictive value of LCx with nonrespiratory specimens was 45.8%.
      CONCLUSION: Critical interpretation of the nucleic acid amplification results
      obtained from nonrespiratory specimens is necessary in both laboratory and
      clinical settings.

PMID- 11310941
TI  - Structure of carotid artery in baboon and rat and differences in their response
      to endothelial denudation angioplasty.
AB  - BACKGROUND: Most studies dealing with vascular response to injury have been
      conducted using rodent and rabbit models, although it is expected that the
      response to injury in these species is dissimilar from man. AIMS: Here we compare
      the structure of native carotid artery in rat and baboon and the response of
      these vessels to endothelial denudation angioplasty. METHODS: In both species,
      the carotid is a musculoelastic artery. Only baboon carotid has a distinct
      intima, correlating in size with the weight of male baboons. Complete endothelial
      denudation of left carotid was performed on eight male baboons and 24 male rats
      by applying an equivalent pull force with a Fogarthy catheter. The animals were
      sacrificed prior to and 15 min and 2, 3, 4, 7, 14 and 28 days postinjury, one
      baboon and three rats per time point. RESULTS: Re-endothelialization in the
      baboon was complete already on day 4, whereas in the rat it was still incomplete
      on day 28. The proliferative response to injury was far smaller in the baboon
      than in the rat, the intimal area increased only by 5-fold in baboon compared
      with 25-fold in rat, and the number of intimal nuclei by 4-fold in baboon
      compared with 12-fold in rat. Complete compensatory remodelling of the lumen size
      occurred in the baboon, whereas in the rat remodelling remained incomplete. The
      cell types participating in the response were, however, similar: deposition of
      thrombocytes on denuded luminal surface, expression of alpha-actin by intimal
      cells, and lack of any significant white cell infiltration in the denuded intima.
      CONCLUSIONS: Baboon carotids are very different from rat carotids both in their
      native structure and in their response to injury. With the limited amount of
      information available from human vessels, baboon carotids closely resemble human
      carotids in both respects.

PMID- 11310942
TI  - Collagens and collagen-related diseases.
AB  - The collagen superfamily of proteins plays a dominant role in maintaining the
      integrity of various tissues and also has a number of other important functions.
      The superfamily now includes more than 20 collagen types with altogether at least
      38 distinct polypeptide chains, and more than 15 additional proteins that have
      collagen-like domains. Most collagens form polymeric assemblies, such as fibrils,
      networks and filaments, and the superfamily can be divided into several families
      based on these assemblies and other features. All collagens also contain
      noncollagenous domains, and many of these have important functions that are
      distinct from those of the collagen domains. Major interest has been focused on
      endostatin, a fragment released from type XVIII collagen, which potently inhibits
      angiogenesis and tumour growth. Collagen synthesis requires eight specific post
      translational enzymes, some of which are attractive targets for the development
      of drugs to inhibit collagen accumulation in fibrotic diseases. The critical
      roles of collagens have been clearly illustrated by the wide spectrum of diseases
      caused by the more than 1,000 mutations that have thus far been identified in 22
      genes for 12 out of the more than 20 collagen types. These diseases include
      osteogenesis imperfecta, many chondrodysplasias, several subtypes of the Ehlers
      Danlos syndrome, Alport syndrome, Bethlem myopathy, certain subtypes of
      epidermolysis bullosa, Knobloch syndrome and also some cases of osteoporosis,
      arterial aneurysms, osteoarthrosis, and intervertebral disc disease. The
      characterization of mutations in additional collagen genes will probably add
      further diseases to this list. Mice with genetically engineered collagen
      mutations have proved valuable for defining the functions of various collagens
      and for studying many aspects of the related diseases.

PMID- 11310943
TI  - Evaluating quality-adjusted life years: estimation of the health utility index
      (HUI2) from the SF-36.
AB  - Quality-adjusted life years (QALYs) are well recognized as a valid measure for
      outcomes in cost-effectiveness analyses. A summary health utility score is
      necessary to evaluate QALYs. The objective of this study was to predict a summary
      utility score (represented by the Health Utility Index [HUI2]) from scores on the
      SF-36. METHODS: A structural equation framework was applied to longitudinal data
      collected from 1992 to 1995 on a sample of patients insured by Southem California
      Kaiser Permanente (N = 6921). An ordinary least squares (OLS) method was used to
      estimate the HUI2. RESULTS: The OLS model on cross-sectional data predicted 50.5%
      of the observed variance in HUI2 scores. Parameter estimates of all SF-36
      components showed statistical significance at the P < 0.05 level. CONCLUSIONS:
      Results of this study provide a quantitative link between two important measures
      of health status. The present model can be used to estimate health utility
      summary scores in studies that have collected SF-36 data.

PMID- 11310944
TI  - Lack of congruence in the ratings of patients' health status by patients and
      their physicians.
AB  - PURPOSE: The purpose of this study was to examine if physician assessments of
      their patients' health status after the medical encounter are comparable to their
      patients' self-assessment of their own health. METHODS: Consecutive patients with
      musculoskeletal diseases were recruited when they attended 1 of the rheumatology
      outpatient clinics selected for the study. Five physicians participated in the
      study, 4 based at an academic center and 1 in the community. Patients were
      interviewed after seeing the physician; they completed health status
      questionnaires (mHAQ and SF-12) and rated their pain, worry about disease, and
      overall health status on visual analog scales. Standard gamble techniques were
      used to obtain patient utilities in relation to their health status, "gambling"
      on the probability of obtaining perfect health from an intervention with varying
      risks of death. After the medical encounter, physicians were asked to rate their
      patients' health status with similar instruments and with standard gamble
      elicitation techniques, blinded to the patients' responses. RESULTS: A total of
      105 patients participated in the study; 70% were female; mean age was 54+/-16
      years; 64% had a connective tissue disease, most commonly rheumatoid arthritis;
      and the other diseases in this group included soft tissue rheumatism,
      osteoarthritis, or low back pain. Statistically significant differences were
      observed between patient and physician ratings for pain, overall health, and
      standard gamble. On average, physicians rated their patients' health status
      higher than the patients themselves and were less willing to gamble on the risk
      of death versus perfect health. Intraclass correlation coefficients (ICC) were
      low: 0.42 for pain, 0.11 for worry, 0.11 for overall health, and 0.04 for
      standard gamble utilities. Similar findings were observed when subgroup analysis
      was performed for individual physicians and for patients with connective tissue
      diseases. No specific patient characteristic consistently related to increased
      divergence in the ratings. CONCLUSIONS: These findings suggest that the
      communication between physicians and their patients at the time of the medical
      encounter needs to be enhanced. An understanding of their patients' health
      perceptions may assist physicians in suggesting appropriate interventions, taking
      into account their patients' benefit-risk preferences.

PMID- 11310945
TI  - Preference for fractures and other glucocorticoid-associated adverse effects
      among rheumatoid arthritis patients.
AB  - OBJECTIVE: The objective of this study was to determine rheumatoid arthritis (RA)
      patients' preferences for validated health state scenarios depicting
      glucocorticoid adverse events, predictors of these preferences, and psychometric
      properties of different preference techniques in this population. METHODS:
      Preferences were elicited by rating scale and time trade-off methods. Time trade
      offs included trading current health for either time spent alive in an adverse
      health state for chronic conditions (time trade-off) or time spent in a sleeplike
      state for acute conditions (sleep trade-off). RESULTS: A total of 107 subjects
      with long-standing RA participated in the preference interviews. Mean preference
      values (rating scale/trade-off) were lowest for serious fracture adverse events,
      including hip fracture requiring a nursing home stay (0.55+/-0.22/0.76+/-0.36)
      and vertebral fracture with chronic pain (0.59+/-0.23/0.67+/-0.35), and highest
      for cataracts (0.84 + 0.17/0.96 0.09) and wrist fracture (0.82+/-0.18/0.81+/
      0.29). Rating scales had a stronger correlation (r= 0.88) with physician ranking
      of scenarios than trade-off methods (r = 0.31). All methods were feasible and
      demonstrated good reliability, while rating scale method showed better construct
      validity than trade-off techniques. CONCLUSION: Relative to their current health,
      RA patients assigned low preference values to many glucocorticoid adverse events,
      particularly those associated with chronic fracture outcomes. Results varied with
      the preference measure used, indicating that methodological attributes of
      preference determinations must be considered in clinical decision making.

PMID- 11310946
TI  - Measuring patients' medical care preferences: care seeking versus self-treating.
AB  - The objectives of this study were (1) to develop a scale to measure patient
      preferences for using medical care, (2) to assess the reliability and validity of
      the scale, and (3) to examine factors predicting preferences. Preferences were
      defined along a continuum, anchored by self-treating preferences and care-seeking
      preferences. A 9-item scale was developed and mailed to a random sample of 3500
      Wisconsin consumers age 50 and older. Ordinary least squares regression was used
      to examine whether preferences were predicted by demographic and health status
      variables. A 56.9% usable response rate was obtained. The Medical Care Preference
      Scale was unidimensional and had a Cronbach's alpha of 0.879. Younger
      individuals, women, individuals in better health, and individuals from rural
      areas had significantly stronger self-treating preferences. Significant
      correlations between the preference scale and 2 measures of health care
      utlization provided evidence of predictive validity. Individuals with care
      seeking preferences used an average of 1.98 more prescription drugs and had 0.50
      more physician visits in the past month than individuals with self-treating
      preferences. The Medical Care Preference Scale should be a useful tool for
      research on health care utilization.

PMID- 11310947
TI  - The role of risk and benefit perception in informed consent for surgery.
AB  - BACKGROUND: Informed consent relies on patients' ability to understand risk
      information. Evidence suggests that people may extract the gist of any risk
      information to make medical decisions. Existing evidence also suggests that there
      is an inverse relationship between the perception of risk and the perception of
      benefit. METHOD: Seventy-one patients on the waiting list for carotid
      endarterectomy (CEA) were surveyed regarding their understanding and recall of
      the risk and benefit to health of undergoing CEA. Patients were surveyed 1 month
      after their initial consultation, and a subgroup was surveyed again on the day
      before their operation. RESULTS: Patients' estimates of their baseline risk of
      stroke without surgery were significantly different from what they had been told
      by the surgeon. Patients' estimates of stroke risk due to surgery ranged from 0%
      to 65% (actual local risk 2%). Patients also had unreasonable expectations about
      the benefit of the operation for their health. Estimates of stroke risk
      correlated positively with the degree of expected benefit from the operation (r =
      0.29, P = 0.05). When resurveyed the day before the operation, patients'
      perceptions of both risk and benefit had increased significantly. The risk
      perception data from some patients appeared to contradict some of the predictions
      of the fuzzy-trace theory. CONCLUSIONS: Most patients failed to understand the
      risks and benefits associated with CEA. Some patients' estimates of stroke risk
      were actually greater than the perceived potential benefit of surgery in terms of
      risk reduction. The data also suggested a positive correlation between the degree
      of perceived benefit and the degree of perceived risk.

PMID- 11310948
TI  - Clinical decision analysis.

PMID- 11310949
TI  - The importance of memory in informed consent for surgical risk.

PMID- 11310950
TI  - Law and ethics.

PMID- 11310951
TI  - Reanalysis of unruptured intracranial aneurysm management: effect of a new
      international study on the threshold probabilities.
AB  - OBJECTIVE: This report updates previous clinical decision analysis for patients
      with unruptured intracranial aneurysm (UN-AN) based on newly published data and
      discusses the role of reanalysis in individual decision making. METHODS: The
      authors employed probabilities for the natural history of UN-AN and results of
      preventive surgery based on the report by the International Study of Unruptured
      Intracranial Aneurysms. Probabilistic sensitivity analysis with Monte Carlo
      simulation and traditional n-way sensitivity analyses were used to assess the
      uncertainty of clinical decisions. RESULTS: The baseline decision in favor of
      preventive surgery is reversed by new data from the international study.
      Probabilistic sensitivity analyses revealed several populations showing
      heterogeneity in terms of strategy selection. One- and two-way sensitivity
      analyses detected two important factors for decision making: annual rupture rate
      and utility for knowingly living with UN-AN. CONCLUSIONS: Annual UN-AN rupture
      rate and the utility for knowingly living with UN-AN are key factors when
      deciding on a therapeutic strategy. Also, updating published decision analyses
      can improve clinical decision making by integrating clinical judgment and newly
      available clinical data.

PMID- 11310952
TI  - Utility elicitation using single-item questions compared with a computerized
      interview.
AB  - BACKGROUND: The use of a simpler procedure for the measurement of utilities could
      affect primarily the variance or both the mean and the variance of measurements.
      In the former case, simpler methods would be useful for population studies of
      preferences; however, in the latter, their use for such studies might be
      problematic. PURPOSE: The purpose of this study was to compare the results of
      utility elicitation using single-item questions to computer elicitation using the
      Ping-Pong search procedure. METHODS: In a convenience sample of 149 primary care
      patients with symptoms of depression, the authors measured and compared standard
      gamble (SG) utilities elicited using a single-item "open question" to SG
      elicitations performed using a computerized interview procedure. Elicitations
      were performed 1 to 2 weeks apart to minimize memory effects. RESULTS: More than
      90% of persons with utilities of 1.0 to the single-item standard gamble had
      utilities of less than 1.0 on the computer SG instrument. Consistent with this
      finding, the mean utilities were lower in computer interviews (0.80 vs. 0.90; P <
      0.0001 for differences). Within subjects, utility measures had only a fair degree
      of correlation (r = 0.54). CONCLUSIONS: Use of single-item questions to elicit
      utilities resulted in less precise estimates of utilities that were upwardly
      biased relative to those elicited using a more complex search procedure.

PMID- 11310955
TI  - Animal electricity, Ca2+ and muscle contraction. A brief history of muscle
      research.
AB  - This brief review attempts to summarize some of the major phases of muscle
      research from Leeuwenhoek's description of sarcomeres in 1674, through Galvani's
      observation of "animal electricity" in 1791, to the discovery of Ca2+ as the key
      messenger in the coupling of nerve excitation to muscle contraction. The emerging
      molecular mechanism of the contraction process is one of the great achievements
      of biology, reflecting the intimate links between physics, chemistry and the life
      Sciences in the solution of biological problems.

PMID- 11310956
TI  - Particulate guanylyl cyclases: multiple mechanisms of activation.
AB  - Cyclic GMP (cGMP), a key messenger in several signal transduction pathways, is
      synthesized from GTP by a family of enzymes termed guanylyl cyclases, which are
      found in two forms: cytosolic (soluble) and membrane-bound (particulate). The
      past decade has brought significant progress in understanding the molecular
      mechanisms that underlie the regulation of particulate guanylyl cyclases and new
      members of their family have been identified. It has become more evident that the
      basic mechanism of catalysis of guanylyl cyclases is analogous to that recognized
      in adenylyl cyclases. Here we review the known basic mechanisms that contribute
      to the regulation of particulate guanylyl cyclases.

PMID- 11310957
TI  - Plasma membrane Ca2+-ATPase in excitable and nonexcitable cells.
AB  - There is a significant number of data confirming that the maintenance of calcium
      homeostasis in a living cell is a complex, multiregulated process. Calcium efflux
      from excitable cells (i.e., neurons) occurs through two main systems--an
      electrochemically driven Na+/Ca2+ exchanger with a low Ca2+ affinity (K0.5 = 10
      15 microM), and a plasmalemmal, specific Ca2+-ATPase, with a high Ca2+ affinity
      (K0.5 < 0.5-1 microM), whereas in nonexcitable cells (i.e., erythrocytes) the
      calcium pump is the sole system responsible for the extrusion of calcium ions.
      The plasma membrane Ca2+-ATPase (PMCA) is a ubiquitously expressed protein, and
      more than 26 transcripts of four PMCA genes are distributed in a tissue specific
      manner. Differences in the structure and localization of PMCA variants are
      thought to correlate with specific regulatory properties and may have
      consequences for proper cellular Ca2+ signaling. The regulatory mechanisms of
      calcium pump activity have been studied extensively, resulting in a new view of
      the functioning of this important molecule in the membranes.

PMID- 11310958
TI  - Mitochondrial potassium and chloride channels.
AB  - Channels selective for potassium or chloride ions are present in inner
      mitochondrial membranes. They probably play an important role in mitochondrial
      events such as the formation of delta pH and regulation of mitochondrial volume
      changes. Mitochondrial potassium and chloride channels could also be the targets
      for pharmacologically active compounds such as potassium channel openers and
      antidiabetic sulfonylureas. This review describes the properties, pharmacology,
      and current observations concerning the functional role of mitochondrial
      potassium and chloride channels.

PMID- 11310959
TI  - Lipid-binding proteins as stabilizers of membrane microdomains--possible
      physiological significance.
AB  - Below the melting point temperature of lipids, artificial lipid membranes usually
      exist in the ordered gel phase. Above these temperatures lipid acyl chains become
      fluid and disordered (liquid-crystalline phase). Depending on the chemical
      composition of artificial membranes, phase separation may occur, leading to the
      formation of transient or stable membrane domains. A similar phase separation of
      lipids into ordered and disordered domains has been observed in natural membranes
      at physiological temperature range. Moreover, it has been reported that certain
      proteins prefer certain organization of lipids, as for example
      glycosylphosphatidylinositol-anchored proteins or Src family of tyrosine kinases.
      The aim of present review is to discuss the possibility that some lipid
      microdomains are induced or stabilized by lipid-binding proteins that under
      certain conditions, for example due to a rise of cytosolic Ca2+ or pH changes,
      may attach to the membrane surface, inducing clustering of lipid molecules and
      creation of ordered lipid microdomains. These domains may than attract other
      cytosolic proteins, either enzymes or regulatory proteins. It is, therefore,
      postulated that lipid microdomains play important roles within a cell, in signal
      transduction and enzymatic catalysis, and also in various pathological states, as
      Alzheimer's disease, anti-phosphatidylserine syndrome, or development of
      multidrug resistance of cancer cells.

PMID- 11310960
TI  - Interaction of membrane skeletal proteins with membrane lipid domain.
AB  - The object of this paper is to review briefly the studies on the interaction of
      red blood cell membrane skeletal proteins and their non-erythroid analogues with
      lipids in model systems as well as in natural membranes. An important question to
      be addressed is the physiological significance and possible regulatory molecular
      mechanisms in which these interactions are engaged.

PMID- 11310961
TI  - Smooth muscle actomyosin promotes Ca2+-dependent interactions between annexin VI
      and detergent-insoluble glycosphingolipid-enriched membrane domains.
AB  - The mechanical link coupling cytoskeletal and contractile proteins to the
      sarcolemma of smooth muscle cells is essential for transmitting tension from the
      cell's interior to exterior. In addition to the well-characterized actin-integrin
      associations present in adhaerens junctions, our recent work has postulated the
      existence of a reversible annexin-dependent membrane-cytoskeleton complex, forged
      in response to a rise in intracellular Ca2+ concentration following smooth muscle
      cell stimulation (Babiychuk et al., J. Biol Chem. 1999, 274, 35191-35195).
      Detailed biochemical characterization of the interactions responsible for the
      formation of this complex revealed that annexins II and VI interact with
      actomyosin, or detergent-insoluble glycosphingolipid-enriched membrane domains
      (rafts) purified from smooth muscle, in a concentration- and Ca2+-dependent
      manner. Annexin II interacted with lipid rafts with high Ca2+-sensitivity, while
      for annexin VI this interaction required non-physiologically high concentrations
      of free Ca2+. However, the Ca2+-sensitivity of the latter interaction strongly
      increased in the presence of purified smooth muscle actomyosin. The detailed
      biochemical analysis of the interactions occurring between annexin II, annexin
      VI, actomyosin and rafts suggests that annexins regulate sarcolemmal organization
      during smooth muscle cell contraction.

PMID- 11310962
TI  - Participation of phospholipase A2 isoforms in the control of calcium influx into
      electrically non-excitable cells.
AB  - The participation of phospholipase A2 isoforms in capacitative store-operated
      Ca2+ influx into Jurkat leukemic T and MDCK cells was investigated. Preincubation
      of Jurkat cells with either bromophenacyl bromide (an inhibitor of secreted
      phospholipase A2, sPLA2) or Helss (an inhibitor of calcium independent
      phospholipase A2--iPLA2) resulted in a significant inhibition of the calcium
      influx. The extent of this inhibition depended on the pH of the extracellular
      millieu; it increased with alkalisation. The rate of Ca2+ influx into MDCK cells
      was reduced by bromophenacyl bromide. Preincubation of these cells with Helss
      resulted in the stimulation of the influx. These observations suggest the
      participation of different PLA2 isoforms in the regulation of Ca2+ influx. They
      also show that the extent that PLA2 isoforms control the influx depends on the pH
      of the medium. Finally, these data indicate that various phospholipase A2
      isoforms may play a role in the control of Ca2+ influx in different cell lines.

PMID- 11310963
TI  - Molecular dynamics simulation studies of lipid bilayer systems.
AB  - The main structural element of biological membranes is a liquid-crystalline lipid
      bilayer. Other constituents, i.e. proteins, sterols and peptides, either
      intercalate into or loosely attach to the bilayer. We applied a molecular
      dynamics simulation method to study membrane systems at various levels of
      compositional complexity. The studies were started from simple lipid bilayers
      containing a single type phosphatidylcholine (PC) and water molecules (PC
      bilayers). As a next step, cholesterol (Chol) molecules were introduced to the PC
      bilayers (PC-Chol bilayers). These studies provided detailed information about
      the structure and dynamics of the membrane/water interface and the hydrocarbon
      chain region in bilayers built of various types of PCs and Chol. This enabled
      studies of membrane systems of higher complexity. They included the investigation
      of an integral membrane protein in its natural environment of a PC bilayer, and
      the antibacterial activity of magainin-2. The latter study required the
      construction of a model bacterial membrane which consisted of two types of
      phospholipids and counter ions. Whenever published experimental data were
      available, the results of the simulations were compared with them.

PMID- 11310964
TI  - Physical properties of lipid bilayer membranes: relevance to membrane biological
      functions.
AB  - Over the last 25 years one of us (WKS) has been investigating physical properties
      of lipid bilayer membranes. In 1991 a group led by WKS was organized into the
      Laboratory of Structure and Dynamics of Biological Membranes, the effective
      member of which is AW. Using mainly the electron paramagnetic resonance (EPR)
      spin-labeling method, we obtained unexpected results, which are significant for
      the better understanding of the functioning of biological membranes. We have
      developed a new pulse EPR spin-labeling method for the detection of membrane
      domains and evaluation of lipid exchange rates. This review will be focused on
      our main results which can be summarized as follows: (1) Unsaturation of alkyl
      chains greatly reduces the ordering and rigidifying effects of cholesterol
      although the unsaturation alone gives only minor fluidizing effects, as observed
      by order and reorientational motion, and rather significant rigidifying effects,
      as observed by translational motion of probe molecules; (2) Fluid-phase model
      membranes and cell plasma membranes are not barriers to oxygen and nitric oxide
      transport; (3) Polar carotenoids can regulate membrane fluidity in a way similar
      to cholesterol; (4) Formation of effective hydrophobic barriers to the permeation
      of small polar molecules across membranes requires alkyl chain unsaturation
      and/or the presence of cholesterol; (5) Fluid-phase micro-immiscibility takes
      place in cis-unsaturated phosphatidylcholine-cholesterol membranes and induces
      the formation of cholesterol-rich domains; (6) In membranes containing high
      concentrations of transmembrane proteins a new lipid domain is formed, with
      lipids trapped within aggregates of proteins, in which the lipid dynamics is
      diminished to the level of gel-phase.

PMID- 11310965
TI  - Influence of amphiphilic compounds on membranes.
AB  - On the basis of Gortel & Grendel (J. Exp. Med., 1925, 41, 439-494) discovery, the
      importance of the lipid bilayer as an integral and indispensible component of the
      cell membrane is discussed. In particular, attention focuses on the interaction
      between membranes and amphiphilic substances. The effect on membranes of
      quaternary ammonium salts, both in the form of pesticides and oxidants as well as
      organic compounds of tin and lead are discussed in greater detail.

PMID- 11310966
TI  - Liposomal drug delivery, a novel approach: PLARosomes.
AB  - Almost from the time of their rediscovery in the 60's and the demonstration of
      their entrapment potential, liposomal vesicles have drawn attention of
      researchers as potential carriers of various bioactive molecules that could be
      used for therapeutic applications in humans and animals. Several commercial
      liposome-based drugs have already been discovered, registered and introduced with
      great success on the pharmaceutical market. However, further studies, focusing on
      the elaboration of more efficient and stable amphiphile-based vesicular (or non
      viral) drug carriers are still under investigation. In this review we present the
      achievements of our group in this field. We have discovered that natural
      amphiphilic dihydroxyphenols and their semisynthetic derivatives are promising
      additives to liposomal lipid compositions. The presence of these compounds in
      lipid composition enhances liposomal drug encapsulation, reduces the amount of
      the lipid carrier necessary for efficient entrapment of anthracycline drugs by a
      factor of two, stabilizes liposomal formulation of the drug (both in suspension
      and in a lyophilized powder), does not influence liposomal fate in the blood
      circulation system and benefits from other biological activities of their
      resorcinolic lipid modifiers.

PMID- 11310967
TI  - Gemini (dimeric) surfactant perturbation of the human erythrocyte.
AB  - We studied the ability of di-cationic gemini surfactantsdi (amphiphiles), i.e.
      1,4-butanediammonium-N,N-dialkyl-N,N,N',N'-tetramethyl bromides (Di-Cm-di-QAS (s
      = 4), where m = 8, 11, 13, 16 and s = the number of alkyl groups in the spacer)
      to induce shape alteration, vesiculation, haemolysis and phosphatidylserine
      exposure in human erythrocytes, and to protect erythrocytes against hypotonic
      haemolysis. At high sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles
      rapidly induced echinocytic (spiculated) shapes and a release of exovesicles,
      mainly in the form of tubes, from the cell surface. Following 60 min incubation
      erythrocytes were sphero-echinocytic and a few cells with
      invaginations/endovesicles were observed. No phosphatidylserine exposure was
      detected. The haemolytic potency increased with an increase of the alkyl chain
      length. At sublytic concentrations the Di-Cm-di-QAS (s = 4) amphiphiles protected
      erythrocytes against hypotonic haemolysis. It is suggested that the Di-Cm-di-QAS
      (s = 4) amphiphiles perturb the membrane in a similar way as single-chain
      cationic amphiphiles, but that they do not easily translocate to the inner
      membrane leaflet.

PMID- 11310968
TI  - The effect of hexadecaprenol on molecular organisation and transport properties
      of model membranes.
AB  - The Langmuir monolayer technique and voltammetric analysis were used to
      investigate the properties of model lipid membranes prepared from
      dioleoylphosphatidylcholine (DOPC), hexadecaprenol (C80), and their mixtures.
      Surface pressure-molecular area isotherms, current-voltage characteristics, and
      membrane conductance-temperature were measured. Molecular area isobars, specific
      molecular areas, excess free energy of mixing, collapse pressure and collapse
      area were determined for lipid monolayers. Membrane conductance, activation
      energy of ion migration across the membrane, and membrane permeability
      coefficient for chloride ions were determined for lipid bilayers. Hexadecaprenol
      decreases the activation energy and increases membrane conductance and membrane
      permeability coefficient. The results of monolayer and bilayer investigations
      show that some electrical, transport and packing properties of lipid membranes
      change under the influence of hexadecaprenol. The results indicate that
      hexadecaprenol modulates the molecular organisation of the membrane and that the
      specific molecular area of polyprenol molecules depends on the relative
      concentration of polyprenols in membranes. We suggest that hexadecaprenol
      modifies lipid membranes by the formation of fluid microdomains. The results also
      indicate that electrical transmembrane potential can accelerate the formation of
      pores in lipid bilayers modified by long chain polyprenols.

PMID- 11310969
TI  - Effect of divalent metal ions on annexin-mediated aggregation of asolectin
      liposomes.
AB  - Annexins belong to a family of Ca2+- and phospholipid-binding proteins that can
      mediate the aggregation of granules and vesicles in the presence of Ca2+. We have
      studied the effects of different divalent metal ions on annexin-mediated
      aggregation of liposomes using annexins isolated from rabbit liver and large
      unilamellar vesicles prepared from soybean asolectin II-S. In the course of these
      studies, we have found that annexin-mediated aggregation of liposomes can be
      driven by various earth and transition metal ions other than Ca2+. The ability of
      metal ions to induce annexin-mediated aggregation decreases in the order: Cd2+ >
      Ba2+, Sr2+ > Ca2+ >> Mn2+ > Ni2+ >> Co2+. Annexin-mediated aggregation of
      vesicles is more selective to metal ions than the binding of annexins to
      membranes. We speculate that not every type of divalent metal ion can induce
      conformational change sufficient to promote the interaction of annexins either
      with two opposing membranes or with opposing protein molecules. Relative
      concentration ratios of metal ions in the intimate environment may be crucial for
      the functioning of annexins within specialized tissues and after treatment with
      toxic metal ions.

PMID- 11310970
TI  - Ion channels-related diseases.
AB  - There are many diseases related to ion channels. Mutations in muscle voltage
      gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated
      channel may lead to such physiological disorders as hyper- and hypokalemic
      periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant
      hyperthermia and myasthenia. Neuronal disorders, e.g., epilepsy, episodic ataxia,
      familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer's
      disease, Parkinson's disease, schizophrenia, hyperekplexia may result from
      dysfunction of voltage-gated sodium, potassium and calcium channels, or
      acetylcholine- and glycine-gated channels. Some kidney disorders, e.g., Bartter's
      syndrome, policystic kidney disease and Dent's disease, secretion disorders,
      e.g., hyperinsulinemic hypoglycemia of infancy and cystic fibrosis, vision
      disorders, e.g., congenital stationary night blindness and total colour-blindness
      may also be linked to mutations in ion channels.

PMID- 11310971
TI  - Regulation of Ca2+ release from internal stores in cardiac and skeletal muscles.
AB  - It is widely accepted that Ca2+ is released from the sarcoplasmic reticulum by a
      specialized type of calcium channel, i.e., ryanodine receptor, by the process of
      Ca2+-induced Ca2+ release. This process is triggered mainly by dihydropyridine
      receptors, i.e., L-type (long lasting) calcium channels, directly or indirectly
      interacting with ryanodine receptor. In addition, multiple endogenous and
      exogenous compounds were found to modulate the activity of both types of calcium
      channels, ryanodine and dihydropyridine receptors. These compounds, by changing
      the Ca2+ transport activity of these channels, are able to influence
      intracellular Ca2+ homeostasis. As a result not only the overall Ca2+
      concentration becomes affected but also spatial distribution of this ion in the
      cell. In cardiac and skeletal muscles the release of Ca2+ from internal stores is
      triggered by the same transport proteins, although by their specific isoforms.
      Concomitantly, heart and skeletal muscle specific regulatory mechanisms are
      different.

PMID- 11310972
TI  - Alzheimer's disease: its origin at the membrane, evidence and questions.
AB  - Numerous results on membrane lipid composition from different regions of
      autopsied Alzheimer's disease brains in comparison with corresponding fractions
      isolated from control brains revealed significant differences in serine- and
      ethanolamine-containing glycerophospholipid as well as in glycosphingolipid
      content. Changes in membrane lipid composition are frequently accompanied by
      alterations in membrane fluidity, hydrophobic mismatch, lipid signaling pathways,
      transient formation and disappearance of lipid microdomains, changes in membrane
      permeability to cations and variations of other membrane properties. In this
      review we focus on possible implications of altered membrane composition on beta
      amyloid precursor protein (APP) and on proteolysis of APP leading eventually to
      the formation of neurotoxic beta-amyloid (A beta) peptides, the major
      proteinaceous component of extracellular senile plaques, directly involved in
      Alzheimer's disease pathogenesis.

PMID- 11310973
TI  - Cellular aspects of folate and antifolate membrane transport.
AB  - Folates--one carbon carriers--take part in the metabolism of purine, thymidylate
      and some amino acids. Internalization of these compounds employs several
      mechanisms of transport systems. Reduced folate carriers and folate receptors
      play the most important role in this process. The physiological role of these
      molecules in normal and neoplastic cells is described regarding changes in
      transport activity and connection of transport systems with resistance to
      antifolates and cancer development.

PMID- 11310974
TI  - Transport of glutathione-conjugates in human erythrocytes.
AB  - The last step of detoxification of both endogenous and environmental toxicants is
      typically a conjugation that produces a bulky hydrophilic molecule. The excretion
      of such conjugates out of cells is of sufficient biological importance to have
      led to the evolution of ATP-driven export pumps for this purpose. The substrate
      specificity of such transporters is broad, and in some cases it has been shown to
      include not only anionic conjugates but also neutral or weakly cationic drugs. In
      the present article, we review the molecular identity, functional and structural
      characteristics of these pumps, mainly on the example of human erythrocytes, and
      discuss their physiological role in detoxification and in the multidrug
      resistance phenotype of cancer cells.

PMID- 11310975
TI  - Transport of organic anions by multidrug resistance-associated protein in the
      erythrocyte.
AB  - The active transport of oxidized glutathione and glutathione S-conjugates has
      been demonstrated for the first time in erythrocytes and this cell remained the
      main subject of research on the "glutathione S-conjugate pump" for years. Further
      studies identifled the "glutathione S-conjugate pump" as multidrug resistance
      associated protein (MRP). Even though cells overexpressing MRP and isolated MRP
      provide useful information on MRP structure and function, the erythrocyte remains
      an interesting model cell for studies of MRP1 in its natural environment,
      including the substrate specificity and ATPase activity of the protein.

PMID- 11310976
TI  - Glycophorin A in two patients with congenital dyserythropoietic anemia type I and
      type II is partly unglycosylated.
AB  - Glycophorins A from erythrocyte membranes of two patients with congenital
      dyserythropoietic anemia type I and type II (CDA type I and II) were analyzed for
      carbohydrate molar composition employing a modification of the recently published
      method that allowed simultaneous determination of carbohydrates and protein in
      electrophoretic bands of glycoproteins separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (Zdebska & Koscielak, 1999, Anal Biochem.,
      275, 171-179). The modification involved a preliminary extraction of erythrocyte
      membranes with aqueous phenol, subsequent electrophoresis and analysis of the
      extracted glycophorins rather than electrophoresis and analysis of the
      glycophorin from intact erythrocyte membranes. The results showed a large deficit
      of N-acetylgalactosamine, galactose, and sialic acid residues in glycophorin A
      from patients with CDA type I and type II amounting to about 45% and 55%,
      respectively. The results strongly suggest that glycophorin A in these patients
      is partly unglycosylated with respect to O-linked glycans. In addition,
      glycophorin A from erythrocytes of a patient with CDA II but not CDA I exhibited
      a significant deficit of mannose and N-acetylglucosamine suggesting that its N
      glycosylation site was also partly unglycosylated.

PMID- 11310977
TI  - Protein C-mannosylation: facts and questions.
AB  - Among the posttranslational modifications of proteins, glycosylation is probably
      the most abundant one. Two main types of protein glycosylation have been known
      for several years, namely N-glycosylation and O-glycosylation. Their biochemical
      properties, structure and biosynthesis, have been described extensively. Their
      biological functions are also known for a number of proteins, although in many
      cases the function remains speculative despite continuous efforts. A few years
      ago, a new type of protein glycosylation was found, which is different from the
      above-mentioned ones. It was called C-glycosylation, since the sugar is linked to
      the protein through a carbon-carbon bond. This article reviews the biochemistry
      of C-glycosylation, the biosynthetic pathway and structural requirements.
      Possible biological functions of this modification are also discussed.

PMID- 11310978
TI  - Size, shape and secondary structure of calponin.
AB  - The overall size and shape of the chicken gizzard calponin (CaP) h1 molecule was
      investigated by dynamic light scattering (DLS) measurements. From the DLS
      experiments, a z-averaged translational diffusion coefficient is derived (5.75 +/
      0.3) x 10(-7) cm(2) s(-1), which corresponds to a hydrodynamic radius of 3.72 nm
      for calponin. The frictional ratio (1.8 for the unhydrated molecule and 1.5 for
      the hydrated one) suggests a pronounced anisotropic structure for the molecule.
      An ellipsoidal model in length 19.4 nm and with a diameter of 2.6 nm used for
      hydrodynamic calculations was found to reproduce the DLS experimental data. The
      evaluation of the secondary structure of CaP h1 from the CD spectra by two
      independent methods has revealed that it contains, on average, 23% helix, 19%
      beta-strand, 18% beta-turns and loops, and 40% of remainder structures. These
      values are in good agreement with those predicted from the amino-acid sequence.
      Predictions used for CaP h1 were applied to other isoforms of known sequences and
      revealed that all calponins share a common secondary structure. Moreover, the
      predicted structure of the calponin CH domain is identical to that found by X-ray
      studies of the spectrin, fimbrin and utrophin CH domains.

PMID- 11310979
TI  - Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia
      coli L-asparaginase.
AB  - Periplasmic Escherichia coli L-asparaginase II with Y25F mutation in the active
      site cavity has been obtained by recombinant techniques. The protein was
      crystallized in a new hexagonal form (P6(5)22). Single crystals of this
      polymorph, suitable for X-ray diffraction, were obtained by vapor diffusion using
      2-methyl-2,4-pentanediol as precipitant (pH 4.8). The crystals are characterized
      by a = 81.0, c = 341.1 A and diffract to 2.45 A resolution. The asymmetric unit
      contains two protein molecules arranged into an AB dimer. The physiologically
      relevant ABA'B' homotetramer is generated by the action of the crystallographic 2
      fold axis along [1, -1, 0]. Kinetic studies show that the loss of the phenolic
      hydroxyl group at position 25 brought about by the replacement of Y with F
      strongly impairs kcat without significantly affecting Km.

PMID- 11310980
TI  - Partial deglycosylation of alpha subunit modifies sturgeon gonadotropin function.
AB  - Chemical deglycosylation (dg) of sturgeon Acipenser gueldenstaedti Br. (alphaGTH)
      resulted in the loss of 83% of its initial carbohydrate content. It altered also
      recombinant dg alphaGTH + betaGTH dimer molecule, reducing its immunoreactivity
      by 30%, and fully blocking the hormonal function. CD spectroscopy showed that
      deglycosylation led to changes in the secondary structure of dg alphaGTH and in
      the alpha-beta recombinant. The sugar moiety of sturgeon alphaGTH is suggested to
      play an important role in maintaining the biological function of the hormone
      dimer molecule.

PMID- 11310981
TI  - The new aspects of aminoacyl-tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases (AARS) are essential proteins found in all living
      organisms. They form a diverse group of enzymes that ensure the fidelity of
      transfer of genetic information from the DNA into the protein. AARS catalyse the
      attachment of amino acids to transfer RNAs and thereby establish the rules of the
      genetic code by virtue of matching the nucleotide triplet of the anticodon with
      its cognate amino acid. Here we summarise the effects of recent studies on this
      interesting family of multifunctional enzymes.

PMID- 11310982
TI  - Densitometric quantification of DNA topoisomers in ethidium bromide-stained
      agarose gels and chemiluminescence-detected X ray films.
AB  - This study investigates the contribution of deformational strain imposed by
      topological interconversions of DNA in ethidium bromide-binding on agarose gels.
      Closed-circular plasmid DNAs were nicked using UV exposure and the DNA bands were
      quantified by densitometry. The results show that the closed circular DNA binds
      the same amount of the dye as its nicked counterpart. The relationship between
      the band intensity on X-ray films of chemiluminescence-detected Southern blots
      and DNA concentration was shown to be linear.

PMID- 11310983
TI  - An optimized recipe for cloning of the polymerase chain reaction-amplified DNA
      inserts into plasmid vectors.
AB  - This study compares a number of parameters that are important in the ligation of
      the polymerase chain reaction-amplified DNA inserts into plasmid vectors and
      their efficient transformation to bacterial cells. The parameters covered were:
      T4 polynucleotide kinase treatment followed by either the large fragment of E.
      coli DNA polymerase or T4 DNA polymerase reactions, the amount of T4 DNA ligase,
      temperature and duration of ligation, molar ratio of insert to vector as well as
      the total DNA concentration. The results show that the T4 polynucleotide kinase
      treated group without further enzymatic manipulation, at an insert to vector
      ratio of 3:1 gave the highest recombination efficiency when 10 microg/ml DNA and
      20 units T4 DNA ligase were applied for ligation for 12 h at 4 degrees C.

PMID- 11310984
TI  - Effect of amyloid beta peptide on poly(ADP-ribose) polymerase activity in adult
      and aged rat hippocampus.
AB  - It is suggested that the fibrillar amyloid beta peptide (A beta) in brain plays a
      direct role in neurodegeneration in Alzheimer's disease, probably through
      activation of reactive oxygen species formation. Free radicals and numerous
      neurotoxins elicit DNA damage that subsequently activates poly(ADP-ribose)
      polymerase (PARP, EC 2.4.2.30). In this study the effect of neurotoxic fragment
      (25-35) of full length A beta peptide on PARP activity in adult and aged rat
      hippocampus was investigated. In adult (4 month old) rat hippocampus the A beta
      25-35 peptide significantly enhanced PARP activity by about 80% but had no effect
      on PARP activity in cerebral cortex and in hippocampus from aged (24-27 month
      old) rats. The effect of A beta peptide was reduced by half by the nitric oxide
      synthase inhibitor N-nitro-L-arginine. Stimulation of glutamate receptor(s)
      itself enhanced PARP activity by about 80% in adult hippocampus. However, A beta
      25-35 did not exert any additional stimulatory effect. These results indicate
      that A beta, through NO and probably other free radicals, induces activation of
      DNA bound PARP activity exclusively in adult but not in aged hippocampus.

PMID- 11310985
TI  - Molecular modelling of the interaction of carbocyclic analogues of netropsin and
      distamycin with d(CGCGAATTCGCG)2.
AB  - A molecular mechanics and molecular dynamics approach was used to examine the
      structure of complexes formed between the d(CGCGAATTCGCG)2 duplex and netropsin,
      distamycin, and four carbocyclic analogues of netropsin and distamycin (1-4). The
      resulting structures of the ligand-DNA model complexes and their energetics were
      examined. It is predicted that the compounds 1-4 should have a decreased affinity
      for the minor groove of AT-rich regions in comparison to netropsin and
      distamycin. From the energetic analysis it appears that van der Waals and
      electrostatic interactions are more important than specific hydrogen bonds in
      stabilizing the ligand-duplex complexes. We predict that compounds 1 and 2 are
      effectively isohelical with the DNA minor groove. The superior DNA-binding
      afforded by 1 and 2 in comparison to 3 and 4 results from their more effective
      penetration into the minor groove and smaller perturbation of molecular structure
      upon complex formation.

PMID- 11310986
TI  - Analysis of the structure-anticancer activity relationship in a set of Schiff
      bases of macrocyclic 2,6-bis(2- and 4-formylaryloxymethyl)pyridines.
AB  - Quantitative estimation of the structure-anticancer activity relationship in a
      series of macrocyclic Schiff bases of 2,6-bis(formylaryloxymethyl)pyridines was
      carried out by the topological approach. Correlation equations describing the
      relationship between the anticancer activity and structural parameters of the
      molecules studied and descriptors characterizing their structure were obtained on
      the basis of in vitro screening data. The influence of structure of the
      investigated substances as reflected by the parameters studied on the anticancer
      activity, was established.

PMID- 11310987
TI  - Determination of adenine nucleotides and their metabolites in human saliva.
AB  - The profile and normal concentrations of nucleotide metabolites in human saliva
      and reproducibility of these determinations were analyzed. Samples of human
      saliva collected from healthy individuals at weekly intervals, were deproteinized
      and analysed for the content of adenine nucleotides and their metabolites by
      reversed-phase HPLC. Initial ATP, hypoxanthine and uric acid concentrations were
      0.52 +/- 0.15 microM, 1.91 +/- 0.37 microM and 184 +/- 22 microM respectively. A
      substantial individual variation persisted within 3 weeks of sampling excepted
      hypoxanthine which showed some unrelated variations. Determination of nucleotides
      and their catabolites in saliva due to its simplicity and reproducibility, may be
      of clinical value in diagnosis of local or systemic disorders.

PMID- 11310988
TI  - Brachyphalangy, feet polydactyly, absent/hypoplastic tibiae: a further case and
      review of main diagnostic findings.
AB  - In 1997, Baraitser et al. (Clin Dysmorphol 6:111-121) described a patient with a
      complex phenotype characterized by facial dysmorphism, micropenis, brachydactyly,
      pre-axial polydactyly of the feet and tibial aplasia. We report here a patient
      with similar features.

PMID- 11310989
TI  - Mandibulofacial dysostosis, microcephaly and thorax deformities in two brothers:
      a new recessive syndrome?
AB  - We report two brothers who presented with mandibulofacial dysostosis, growth
      retardation, microcephaly, thoracic deformities and conductive hearing loss along
      with asplenia in one case and aplasia of the gallbladder in the other. The
      pattern of malformations differs significantly from established syndromes with
      mandibulofacial dysostosis such as Nager syndrome or Genee-Wiedemann syndrome and
      also from cerebro-costo-mandibular syndrome. As chromosome analysis revealed
      normal male karyotypes, we consider this to be a distinct heritable syndrome that
      may be either autosomal recessive or X-chromosomal recessive.

PMID- 11310990
TI  - Two brothers with severe developmental delay, growth retardation and unusual
      appearance.
AB  - We report on two brothers with short stature, severe developmental delay and
      unusual appearance. Several conditions including the Russell-Silver, Dubowitz,
      Floating-Harbour and Cockayne syndromes were considered in the differential
      diagnosis, but subsequently rejected. These two cases are likely to represent a
      new autosomal recessive or X-linked recessive syndrome.

PMID- 11310991
TI  - Diagnostic dilemmas in four infants with nephrotic syndrome, microcephaly and
      severe developmental delay.
AB  - We present four cases with nephrotic syndrome, microcephaly and severe
      developmental delay. In the differential diagnosis the Galloway-Mowat syndrome,
      PEHO syndrome, ARC syndrome and the carbohydrate-deficient glycoprotein (CDG)
      syndrome are considered and discussed. One case may fall into the Galloway-Mowat
      spectrum and another case was diagnosed with the CDG syndrome. This case is the
      third report of a nephrotic syndrome as a part of the CDG syndrome. Two remaining
      cases with cerebellar and brain stem atrophy, and without major histopathological
      changes in the kidney were left without a definite unifying diagnosis and may
      well represent a different unknown condition. Although microcephaly and nephrotic
      syndrome with or without hiatus hernia has been equated with Galloway-Mowat
      syndrome in the literature, the brain and renal pathology in these reported cases
      has been very variable. It is likely that this group as a whole is aetiologically
      heterogeneous.

PMID- 11310992
TI  - An atypical case suggesting the possibility of overlap between Malpuech and
      Juberg-Hayward syndromes.
AB  - Malpuech syndrome and Juberg-Hayward syndrome are considered to be distinct
      disorders of orofacial clefting. We present details of a patient whose clinical
      presentation closely resembles the profile of Malpuech syndrome, but whose
      radiological features are more in keeping with published observations in Juberg
      Hayward patients.

PMID- 11310993
TI  - A new familial syndrome with facial abnormalities, abnormal EEG, and mental
      retardation.
AB  - Two sisters are reported with up-slanting palpebral fissures, hypertelorism,
      ptosis, a broad, bifid nasal tip, a high-arched palate, mental retardation,
      abnormal EEG and hand malformations in one of the patients. The girls' parents
      originate from the same village. Although the findings resemble the recently
      defined neurofaciodigitorenal syndrome, some findings suggest that this is a
      newly recognized syndrome.

PMID- 11310994
TI  - A new case of Myhre syndrome.
AB  - Myhre Syndrome is a rare condition associated with mental retardation, short
      stature, generalized muscle hypertrophy, cardiac defects and a distinct facial
      appearance. There have only been five reported cases and we now present a sixth,
      together with a review of the clinical features of this syndrome.

PMID- 11310995
TI  - Inherited duplication of Xq27.2-->qter: phenocopy of infantile Prader-Willi
      syndrome.
AB  - A male is described with familial duplication of the distal long arm of the X
      chromosome (Xq27.2-->qter) at the distal short arm (Xp22.3). The proband has
      features of the male Prada-Willi syndrome phenotype that have not previously been
      reported in other males with duplication of Xq27-->qter.

PMID- 11310996
TI  - Toriello-Carey syndrome: an additional case and summary of previously reported
      cases.
AB  - We report an additional case of Toriello-Carey syndrome, a rare multiple
      malformation syndrome, and present a summary of previously reported cases.

PMID- 11310997
TI  - Long-term survival in Patau syndrome.
AB  - A female patient with an extra chromosome 13 (Patau syndrome) is described. There
      are only five previous reports of patients with trisomy 13 who have survived past
      the first decade. It is concluded that non-lethal congenital anomalies and
      aggressive medical care play an important role in the survival of patients with
      trisomy 13.

PMID- 11310998
TI  - Molecular cytogenetics and phenotype characterization of a de novo pure partial
      trisomy 10(q24.33-qter).
AB  - The molecular-cytogenetic characterization of a de novo pure partial trisomy
      10(q24.33-qter) is described. This report provides information about the
      postnatal phenotype. The clinical findings observed in this case support the
      conclusion that the more severe disease related genes are located between 10q24.1
      and q24.33.

PMID- 11310999
TI  - Bowen-Conradi syndrome in an Indian infant: first non Hutterite case.
AB  - An Indian male infant with the lethal Bowen Conradi syndrome is described. This
      is the first case in the literature who is not from the Hutterite population.

PMID- 11311000
TI  - Cerebro-fronto-facial syndrome: three types?

PMID- 11311001
TI  - Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies,
      macrostomia, mental retardation and CNS structural anomalies: defining the
      phenotype.
AB  - We report a Brazilian boy, born to normal and nonconsanguineous parents showing,
      among other signs, brachycephaly, a wide forehead, a widow's peak, hypertelorism,
      wide palpebral fissures with multiple eyelid colobomas, a broad nasal root, a
      long philtrum, macrostomia, prominent lips, a high arched palate, a midline
      alveolar cleft, a small and grooved chin, ear anomalies, structural anomaly of
      the corpus callosum, and mental retardation. To our knowledge this additional
      patient defines a particular clinical condition previously reported [Guion
      Almeida M.L. Richieri-Costa A. (1999) Clinical Dysmorphol 8;1-4; Masuno M. et al.
      (2000) Clin Dysmorphol 9:59-60].

PMID- 11311002
TI  - A new syndrome with craniofacial and skeletal dysmorphisms and developmental
      delay.
AB  - We report a 16-year-old boy with multiple craniofacial and skeletal dysmorphic
      features including brachycephaly, acrocephaly, hypertelorism, wide palpebral
      fissures, broad nose, anteverted nares, broad columella, long and smooth
      philtrum, thin upper lip, macrostomia, carp-like mouth, micrognathia, low-set and
      posteriorly angulated ears with small and abnormal pinnae, a low posterior
      hairline, a short neck, hypoplastic and widely-spaced nipples, multiple severe
      pterygia, an umbilical hernia, metatarsus varus, low implantation of the
      halluces, and delayed motor and language development. An MRI of the head showed
      bilateral frontal pachygyria but no sign of heterotopia. The unique features of
      our patient suggest that he represents a new syndrome.

PMID- 11311003
TI  - Total anomalous pulmonary venous connection and a constellation of craniofacial,
      skeletal, and urogenital anomalies in a newborn and similar features in his 36
      year-old father.
AB  - We report on a newborn male born to non-consanguineous parents with total
      anomalous pulmonary venous connection (TAPVC) and additional findings of
      malformed ears, hypertelorism, brachyphalangy in the hands, pterygium of the
      elbows, knees, and wrists, complex lower limb pre-axial polydactyly, tibial
      shortening, clubfeet, horseshoe kidney and a micropenis. He had a 46,XY
      karyotype. His 36-year-old father had similar craniofacial and limb anomalies
      suggesting an autosomal dominant syndrome with variable expression. Our patients
      may represent the 3rd and 4th examples of a newly-described syndrome by Baraitser
      et al. [(1997) Clin Dysmorphol 6:111-121] which is distinguished by malformed
      ears, complex pre-axial polydactyly and tibial aplasia in the lower limbs, severe
      brachyphalangy in the hands, and a micropenis.

PMID- 11311004
TI  - Protein-chemical analysis of Bio-Oss bone substitute and evidence on its
      carbonate content.
AB  - The natural bone substitute Bio-Oss is used in periodontal and maxillofacial
      surgery to fill bone defects and permit reossification. Recent reports have
      suggested the presence of TGFbeta and of substantial amounts of protein in Bio
      Oss and have questioned its position as a biologically inert material and its
      safety in clinical applications (Honig et al., Plast Reconstr Surg 1999;103:1324;
      Schwartz et al., J Periodontol 2000;71:1258). Bio-Oss was therefore subjected to
      a detailed biochemical, histochemical and biophysical analysis. In three
      different types of extracts of Bio-Oss no evidence for the presence of protein
      based on SDS-PAGE and silver staining was detected. In addition, as shown by
      Western blotting, there was no immunochemical evidence for the presence of the
      potential growth-inducing factor TGFbeta. Furthermore, micropolished sections of
      Bio-Oss failed to be stained with McNeal's Tetrachrome as did microtome sections
      treated with Goldner's Trichrome. However, Bio-Oss was strongly stained with the
      protein dye Coomassie blue. This staining was virtually irreversible and is
      attributed to the carbonate content of Bio-Oss which was detected by
      thermogravimetry-mass spectrometry. Thus, within the limits of the assay
      conditions, Bio-Oss does not contain protein material to a measurable extent.

PMID- 11311005
TI  - In vivo evaluation of bone-bonding of titanium metal chemically treated with a
      hydrogen peroxide solution containing tantalum chloride.
AB  - Apatite formation on implants is important in achieving a direct bonding to bone
      tissue. We recently showed that titanium metal chemically treated with a hydrogen
      peroxide solution containing tantalum chloride has the ability to form a
      hydroxyapatite layer in simulated body fluid which had inorganic ion composition
      similar to human blood plasma. In this study, a pure titanium cylinder (4.0 mm in
      diameter, 20.0 mm in length) treated with this method was implanted into a hole
      (4.2 mm in diameter) in a rabbit's tibia. After implantation for predetermined
      periods up to 16 weeks, the specimens were extracted with bone tissue, and were
      examined by push-out test to evaluate the shearing force between the implant and
      bone tissue. The results were compared with those of non-treated pure titanium.
      Eight weeks after surgery, the shearing force of the treated titanium implanted
      in the 4.2 mm-hole was significantly higher than that of non-treated titanium,
      although the surface roughness was not changed after the treatment. Scanning
      electron microscopic (SEM) observation and energy-dispersive X-ray (EDX)
      microanalysis showed that the bone comes very close to the surface of the treated
      titanium. Moreover, the shearing force was higher for the implanted sample in the
      4.0 mm-hole than that in the 4.2 mm-hole. Thus, it is confirmed that the
      treatment with hydrogen peroxide solution containing tantalum chloride provides
      higher bonding ability on titanium implants in vivo.

PMID- 11311006
TI  - A new approach based on injection moulding to produce biodegradable starch-based
      polymeric scaffolds: morphology, mechanical and degradation behaviour.
AB  - One of the present challenges in polymer scaffold processing is the fabrication
      of three-dimensional (3D) architectures with an adequate mechanical performance
      to be used in the tissue engineering of hard tissues. This paper describes a
      preliminary study on the development of a new method to produce biodegradable
      scaffolds from a range of corn-starch-based polymers. In some cases,
      hydroxlapatite was also used as a reinforcement of the biodegradable polymers.
      The developed methodology consists of a standard conventional injection moulding
      process, on which a solid blowing agent based on carboxylic acids is used to
      generate the foaming of the bulk of the moulded part. The proposed route allows
      for the production of scaffolds with a compact skin and a porous core, with
      promising mechanical properties. By using the developed method it is possible to
      manufacture biodegradable polymer scaffolds in an easy (melt-based processing)
      and reproducible manner. The scaffolds can be moulded into complex shapes, and
      the blowing additives do not affect the non-cytotoxic behaviour of the starch
      based materials. The materials produced using this method were evaluated with
      respect to the morphology of the porous structure, and the respective mechanical
      properties and degradation behaviour. It was demonstrated that it is possible to
      obtain, by a standard melt based processing route, 3D scaffolds with complex
      shapes that exhibit an appropriate morphology, without decreasing significantly
      the mechanical properties of the materials. It is believed that the optimisation
      of the proposed processing methodology may lead to the production of scaffolds
      that might be used on the regeneration of load-bearing tissues.

PMID- 11311007
TI  - Urea permeation and hydrolysis through hollow fiber dialyzer immobilized with
      urease.
AB  - The surface of commercial polyacrylonitrile hollow fibers was hydrolyzed and
      covalently bonded with urease by using glutaraldehyde. Mini-modules assembled
      with these modified hollow fibers were then used to study the effect of
      concentration of glutaraldehyde, pH, and temperature on the catalysis of urea.
      The immobilized amount increased with the concentration of glutaraldehyde.
      However, urease immobilized with 5% glutaraldehyde had higher activity (0.38
      micromol/min/mg-urease) than with other concentrations. The activity of the
      immobilized urease remained at above 0.32 micromol/min/mg-urease over wider
      applicable ranges of temperature (4-70 degreesC) and pH (5-8) compared to free
      urease. For comparison, the activity of immobilized urease was 0.35
      micromol/min/mg-urease, while that for non-immobilized urease was 0.33
      micromol/min/mg-urease at pH 7 and 20 degreesC. The removal of urea using urease
      immobilized dialyzer was demonstrated with in-vitro dialysis and showed faster
      removing rate of urea than a regular dialyzer by 2.7 times.

PMID- 11311008
TI  - Setting characteristics and mechanical behaviour of a calcium phosphate bone
      cement containing tetracycline.
AB  - Calcium phosphate cements are used for bone defect filling and they may also be
      used as delivery systems for active agents. The physicochemical behaviour of an
      ionic cement, with a final composition of hydroxyapatite, containing tetracycline
      hydrochloride was investigated. Chemical characterisation, X-ray diffraction
      analysis, compressive strength and tensile strength were performed. It is known
      that the antibiotic can be adsorbed on calcium phosphate compounds and the
      presence of chloride ions can strongly influence the behaviour of the cement.
      Adding more than 1% (w/w) of 95% pure tetracycline hydrochloride in the solid
      phase led to a cement with poor mechanical properties, but which, in addition to
      hydroxyapatite, contained residual starting reagents. For this reason,
      experiments were also performed with tetracycline previously treated with a
      calcium sulphate solution. Using a treated tetracycline, it was possible to
      introduce at least 7% (w/w) of active ingredient whilst still allowing the
      reaction to proceed to completion i.e. the formation of hydroxyapatite with good
      mechanical properties. Therefore, treating the tetracycline HCI with calcium
      sulphate solution prior to reaction conserved the activity of the antibiotic,
      limited the influence of the antibiotic on the cement evolution and retained the
      physical properties of the cement.

PMID- 11311009
TI  - Physico-chemical characterisation of carboxymethylated spun cellulose fibres.
AB  - A new fibrous material for the treatment of exudative wounds is characterised in
      terms of its physico-chemical properties. The chemistry of the material is
      analysed and its crystalline structure hypothesised. The influence of the
      structure on the hydration properties of the carboxymethylated cellulose fibre in
      fabric form is also demonstrated by physical test methods in comparison with
      fibrous alginate dressings. The methods illustrate the ability of the material to
      immobilise fluid by gel blocking and suggest how this can be beneficial in the
      treatment of chronic wounds by protecting the delicate peri-ulcer area from
      maceration by exudate.

PMID- 11311010
TI  - An evaluation of the capacity of differently prepared demineralised bone matrices
      (DBM) and toxic residuals of ethylene oxide (EtOx) to provoke an inflammatory
      response in vitro.
AB  - Demineralised bone matrix (DBM) is a form of allogeneic tissue graft widely used
      in oral and maxillofacial procedures. There is a long history of controversy
      relating to the suitability of ethylene oxide gas (EtOx) as a terminal
      sterilisation agent for this graft, relating to its effects on the clinical
      performance of the grafts. Furthermore, the generation of a toxic residual
      chemical (ethylene chlorohydrin, ECl) during the ethylene oxide sterilisation of
      patellar tendon allografts has been implicated in the failure of these grafts
      owing to the induction of a localised inflammatory response. In this study we
      have investigated the capacity of a range of different DBM preparations, and ECl
      dilutions, to induce the production of three pro-inflammatory cytokines,
      interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and tumour necrosis factor
      alpha (TNF-alpha) from human peripheral blood mononuclear cells (PBMNCs). The
      levels of EtOx and ECl in EtOx terminally sterilised DBM and mineralised bone
      grafts were measured by gas chromatography. It was found that the only factor
      capable of rendering DBM pro-inflammatory was the presence of small (<20
      micrometre diameter) DBM particles. No other processing or sterilisation
      technique resulted in the DBM becoming pro-inflammatory. Although it was also
      found that DBM, when EtOx-sterilised, retained more ECI than mineralised bone
      grafts following a standard EtOx sterilisation protocol, ECl did not provoke an
      inflammatory response in vitro at levels up to and including those which are
      cytotoxic to PBMNCs.

PMID- 11311011
TI  - A novel mucoadhesive polymer prepared by template polymerization of acrylic acid
      in the presence of chitosan.
AB  - A novel mucoadhesive polymer was prepared by template polymerization of acrylic
      acid in the presence of chitosan for transmucosal drug delivery system (TMD). FT
      IR results indicated that polymer complex was formed between poly(acrylic acid)
      (PAA) and chitosan through hydrogen bonding. Glass transition temperature (Tg) of
      chitosan and PAA in the PAA/chitosan polymer complexes was inner-shifted compared
      with Tg of chitosan and PAA itself. This may be due to the increased miscibility
      of PAA with chitosan through the hydrogen bonding. The crystallinity of chitosan
      in the PAA/chitosan polymer complexes was decreased with polymer complex
      formation with PAA. The dissolution rate of the PAA/chitosan polymer complex was
      dependent on pH and ratio of PAA/chitosan. The mucoadhesive force of PAA/chitosan
      polymer complex was similar to a commericial product, Carbopol 971P NF.

PMID- 11311012
TI  - Release of protein from highly cross-linked hydrogels of poly(ethylene glycol)
      diacrylate fabricated by UV polymerization.
AB  - Highly crosslinked hydrogel spheres were fabricated using UV photopolymerization
      of poly(ethylene glycol) diacrylate (PEG-DA) and pentaerythritol triacrylate
      (PETA) with 2,2'-dimethoxy-2-phenyl-acetophenone (DMPA) as the photoinitiator.
      Spheres were fabricated both with and without one of three comonomers: acrylic
      acid, acrylamide or allylamine. Photopolymerization rates and polymer morphology
      were determined using attenuated total reflectance/Fourier transform infrared
      spectroscopy and electron microscopy, respectively. These gels were further
      characterized for volume change, equilibrium water content, diffusivity of the
      expanding gel, molecular weight between crosslinks and polymer mesh size.
      Hydrogels with comonomers generally demonstrated an increase in equilibrium water
      content, average molecular weight between crosslinks and mesh size. Bovine serum
      albumin was incorporated into the hydrogel to simulate delivery of a model
      protein drug. The protein diffusion coefficients, based a Fickian release model,
      were calculated to be between 10(-10) and 10(-12) cm2/s with slight variance due
      to PETA concentration and the type of comonomer used.

PMID- 11311013
TI  - The microenvironment of immobilized Arg-Gly-Asp peptides is an important
      determinant of cell adhesion.
AB  - This paper uses self-assembled monolayers on gold as a model system to
      demonstrate that the attachment and spreading of Swiss 3T3 fibroblasts depends
      strongly on the microenvironment of immobilized RGD peptides. This work utilized
      monolayers that present mixtures of Arg-Gly-Asp peptides, which are ligands for
      cellular integrin receptors, and oligo(ethylene glycol) groups, which resist the
      nonspecific adsorption of protein. The microenvironment of the peptide ligands
      was controlled by altering the length of the surrounding oligo(ethylene glycol)
      groups on the monolayer. By using thiols that present either tri-, tetra-, penta
      , or hexa(ethylene glycol) units, the average distance separating the glycol
      groups and the peptide ligand is altered while the structure and properties of
      the background remain unchanged. Cell attachment to monolayers presenting a fixed
      density of peptide decreased as the length of the oligo(ethylene glycol) group
      increased. The average projected area of attached cells showed a similar trend.
      At lower densities of immobilized peptide, decreases in both cell attachment and
      projected cell area were more pronounced. Attachment and spreading did not depend
      on density of peptide on monolayers presenting tri(ethylene glycol) groups, but
      showed a high sensitivity to density of ligand on monolayers presenting longer
      glycol oligomers. Experiments that used a soluble peptide to inhibit the
      attachment of cells to monolayers demonstrated that the strength of the cell
      substrate interaction decreased on monolayers presenting longer glycol groups.
      Together, these results suggest that the microenvironment of the peptide ligand
      influences the affinity of the integrin-peptide interaction and that weaker
      interactions display a density-dependent enhancement of binding during cell
      attachment and spreading. This finding is an important consideration in studies
      that correlate biological function with the composition of ligands on a
      substrate. This finding also represents an important principle for the design of
      biologically active materials because it illustrates the degree to which the
      presentation of adhesion motifs can modify the response of mammalian cells.

PMID- 11311014
TI  - In vitro evaluation of the bioadhesive properties of hydrophobic polybasic gels
      containing N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate.
AB  - The bioadhesive properties of the hydrophobic, basic polyelectrolyte hydrogel
      disks containing crosslinked N,N-dimethylaminoethyl methacrylate-co-methyl
      methacrylate 30/70mol% were evaluated in vitro using gastric (pH 1.2), sublingual
      (pH 6.5), vaginal (pH 4.0) and intestinal (pH 7.5) pig's mucosas. Adhesive
      strength was measured using a modified Du Nouy tensiometer by measuring the force
      of detachment between a gel disk and the respective mucosa. The effect of
      crosslinker content in the gel was evaluated. It was found an increase in the
      adhesive strength with the increase of crosslinker content in the pH range of 4.0
      7.5. For the evaluation at pH 1.2 (gastric mucosa) the opposite behavior was
      observed. The results indicate that initial bioadhesive contact may be the result
      of surface energy effects and/or electrostatic interactions of oppositely charged
      groups between mucin and the gel. In some cases, mucus dehydration may also be
      involved. When the gel is swollen, chain interpenetration also plays a roll in
      the bioadhesive interaction. The gels presented bioadhesive forces in gastric and
      vaginal mucosas (acidic medium), similar to the adhesive forces of well-known
      bioadhesives such as hydroxymethylcellulose and sodium alginate to the intestinal
      mucosa. The results indicate that hydrophobic polybasic gels present bioadhesive
      properties that make them suitable for site specific, pH controlled drug
      delivery.

PMID- 11311015
TI  - Porous calcium polyphosphate scaffolds for bone substitute applications -- in
      vitro characterization.
AB  - Porous structures were formed by gravity sintering calcium polyphosphate (CPP)
      particles of either 106-150 or 150-250 microm size to form samples with 30-45
      vol% porosity with pore sizes in the range of 100 microm (40-140 microm). Tensile
      strength of the samples assessed by diametral compression testing indicated
      relatively high values for porous ceramics with a maximum strength of 24.1 MPa
      for samples made using the finer particles (106-150 microm). X-ray diffraction
      studies of the sintered samples indicated the formation of beta-CPP from the
      starting amorphous powders. In vitro aging in 0.1 M tris-buffered solution (pH
      7.4) or 0.05 M potassium hydrogen phthalate buffered solution (pH 4.0) at 37
      degreesC for periods up to 30d indicated an initial rapid loss of strength and P
      elution by 1 d followed by a more gradual continuing strength and P loss
      resulting in strengths at 30d equal to about one-third the initial value. The
      observed structures, strengths and in vitro degradation characteristics of the
      porous CPP samples suggested their potential usefulness as bone substitute
      materials pending subsequent in vivo behaviour assessment.

PMID- 11311016
TI  - New methods for the assessment of in vitro and in vivo stress cracking in
      biomedical polyurethanes.
AB  - This article describes a new test method for the assessment of the severity of
      environmental stress cracking of biomedical polyurethanes in a manner that
      minimizes the degree of subjectivity involved. The effect of applied strain and
      acetone pre-treatment on degradation of Pellethane 2363 80A and Pellethane 2363
      55D polyurethanes under in vitro and in vivo conditions is studied. The results
      are presented using a magnification-weighted image rating system that allows the
      semi-quantitative rating of degradation based on distribution and severity of
      surface damage. Devices for applying controlled strain to both flat sheet and
      tubing samples are described. The new rating system consistently discriminated
      between the effects of acetone pre-treatments, strain and exposure times in both
      in vitro and in vivo experiments. As expected, P80A underwent considerable stress
      cracking compared with P55D. P80A produced similar stress crack ratings in both
      in vivo and in vitro experiments, however P55D performed worse under in vitro
      conditions compared with in vivo. This result indicated that care must be taken
      when interpreting in vitro results in the absence of in vivo data.

PMID- 11311017
TI  - Porcelain adherence to dental cast CP titanium: effects of surface modifications.
AB  - OBJECTIVES: A reaction layer forms on cast titanium surfaces due to the reaction
      of the molten titanium with the investment material. Such a layer prevents strong
      adhesion between titanium and porcelain. This study characterized the effects of
      surface modifications on cast titanium surfaces and titanium-ceramic adhesion.
      METHODS: ASTM grade II CP titanium was cast into an MgO-based mold. Castings were
      devested by sandblasting with alumina particles, and subjected to surface
      modification by immersion in one of the following solutions: (1) 35% HNO3-5% HF
      at room temperature for 1min; (2) 50% NaOH-10% CuSO4 x 5H2O at 105 degreesC for
      10min; (3) the NaOH-CuSO4 solution followed by the HNO3-HF solution; (4) 50% NaOH
      10% NaSO4 at 105 degreesC for 10 min; (5) the NaOH-NaSO4 solution followed by the
      HNO3-HF solution; and (6) 50% NaOH solution at 105 degreesC for 10min. Surfaces
      only sandblasted with alumina were used as controls. Specimen surfaces were
      characterized by XRD and SEM/EDS, and hardness-depth profiles were determined.
      All specimens were sandblasted with 110 microm alumina particles before porcelain
      firing. An ultra-low-fusing porcelain (Vita Titankeramik) was fused on the
      titanium surfaces. The titanium-ceramic adhesion was characterized by a biaxial
      flexure test, and area fraction of adherent porcelain (AFAP) was determined by X
      ray spectroscopy. RESULTS: EDS analyses revealed a substantial amount (13-17 wt%)
      of Al on the control, and specimens modified with Methods 2, 4, and 6. XRD
      revealed residual stress in the titanium surfaces and corundum on the control,
      and Methods 2, 4, and 6 specimens. A new Ti(Cu, Al)2 phase was identified on the
      titanium surfaces modified by immersion in 50% NaOH-10% CuSO4 x 5H2O aqueous
      solution. Reduced residual stress was observed on Method 1, 3, and 5 specimens.
      No corundum peaks were detected on these specimens. Compared to the control,
      significantly lower (P < 0.05) hardness values were found for Methods 1-3 and
      Method 5 specimens at 20 microm below the surfaces and for Method 1-5 specimens
      at 50 microm below the surfaces. Significantly higher (P < 0.05) AFAP values were
      found for surfaces modified with Methods 2-6 compared to the control and Method
      1, and no significant differences were found among Methods 1-6, and between
      control and Method 1. SIGNIFICANCE: Based on the results from the present study,
      porcelain adherence to cast CP titanium can be improved by the caustic baths used
      in the study.

PMID- 11311018
TI  - In vitro characterisation of zirconia coated by bioactive glass.
AB  - An in vitro evaluation of a biomedical device, which combines the mechanical
      properties of zirconia substrates with the bioactivity of two different glass
      layers (AP40 and RKKP), was performed. In this work, data on different kinds of
      analysis were reported both on as-sintered zirconia samples and on RKKP- and AP40
      coated zirconia substrates. Structure, composition and morphology of the apatite
      layer growth on the coated samples after 30 days of soaking in an acellular
      simulated body fluid, serum protein adsorption, fibroblasts and human osteoblast
      like cells adhesion, growth, morphology and biochemical aspects were studied.
      Results of soaking test in SBF, revealed the growth of an apatite layer on the
      surface of the glass-coated samples. Proteins adsorbed to the materials were
      analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and
      results evidenced that the two glass-coated materials bound a higher amount of
      total protein than did the zirconia substrate. Fibroblasts and osteoblast-like
      cells cultured on RKKP- and AP40-coated zirconia showed a higher proliferation
      rate, leading to confluent cultures with higher cell density and a generally
      better expression of osteoblast alkaline phosphatase activity in comparison with
      zirconia substrate. In conclusion, our results indicate that the surface chemical
      characteristics of the two glass coatings AP40 and RKKP, with no great
      differences between them, substantially enhance zirconia integration with bone
      cells at least in vitro. This effect may be of significance in the stability of
      glass-coated zirconia orthopaedic and dental implants.

PMID- 11311019
TI  - Poly(ethylene glycol)-poly(L-lactide) diblock copolymer prevents aggregation of
      poly(L-lactide) microspheres during ethylene oxide gas sterilization.
AB  - Sterilization procedure is one of the most important obstacles in the clinical
      applications of biodegradable microspheres. The microspheres prepared with
      poly(alpha-hydroxy acid) were severely aggregated during ethylene oxide (EO) gas
      sterilization, and could not be used in clinical applications. In this study, the
      effects of EO gas sterilization on the poly(L-lactide) (PLLA) microspheres were
      analyzed by nuclear magnetic resonance spectroscopy (1H-NMR), differential
      scanning calorimetry (DSC), gel permeation chromatography (GPC), scanning
      electron microscope (SEM) and size fractionation. The aggregation between the
      microspheres might be stimulated by high mobility of amorphous regions of PLLA on
      the microsphere surfaces since both water vapor and gas mixture can reduce glass
      transition temperature (Tg) of PLLA below the sterilization temperature. During
      EO gas sterilization, there were no changes in the molecular structure and the
      molecular weight of PLLA in microspheres, but there were changes in the
      crystallinity of PLLA in microspheres. In this study, poly(L-lactide)
      poly(ethylene glycol) diblock copolymers (PLE) were blended with PLLA
      homopolymers in various ratios to design the microsphere suitable for EO gas
      sterilization. Aggregation of PLLA microspheres was markedly prevented when more
      than 4wt% of PLE was blended in the microspheres. This inhibition effect on
      aggregation may be due to the increased initial crystallinity of the
      microspheres, which help to maintain the microsphere morphology during EO gas
      sterilization.

PMID- 11311020
TI  - What is sufficient 'new knowledge' to justify a publication?

PMID- 11311021
TI  - The effect of recovery duration on running speed and stroke quality during
      intermittent training drills in elite tennis players.
AB  - The aim of this study was to assess the effect of the recovery duration in
      intermittent training drills on metabolism and coordination in sport games. Ten
      nationally ranked male tennis players (age 25.3+/-3.7 years, height 1.83+/-0.8 m,
      body mass 77.8+/-7.7 kg; mean +/- sx) participated in a passing-shot drill
      (baseline sprint with subsequent passing shot) that aimed to improve both
      starting speed and stroke quality (speed and precision). Time pressure for stroke
      preparation was individually adjusted by a ball-machine and corresponded to 80%
      of maximum running speed. In two trials (T10, T15) separated by 2 weeks, the
      players completed 30 strokes and sprints subdivided into 6 x 5 repetitions with a
      1 min rest between series. The rest between each stroke-and-sprint lasted either
      10 s (T10) or 15 s (T15). The sequence of both conditions was randomized between
      participants. Post-exercise blood lactate concentration was significantly
      elevated in T10 (9.04+/-3.06 vs 5.01+/-1.35 mmol x l(-1), P < 0.01). Running time
      for stroke preparation (1.405+/-0.044 vs 1.376+/-0.045 s, P < 0.05) and stroke
      speed (106+/-12 vs 114+/-8 km x h(-1), P < 0.05) were significantly decreased in
      T10, while stroke precision - that is, more target hits (P < 0.1) and fewer
      errors (P < 0.05) - tended to be higher. We conclude that running speed and
      stroke quality during intermittent tennis drills are highly dependent on the
      duration of recovery time. Optimization of training efficacy in sport games (e.g.
      combined improvement of conditional and technical skills) requires skilful fine
      tuning of monitoring guidelines.

PMID- 11311022
TI  - Differences between the sexes and age-related changes in orienteering speed.
AB  - The aim of this study was to assess the effects of the age and sex of the
      competitor on orienteering speed during competitive events. The results of the
      fastest three male and fastest three female competitors in each 5-year age band
      (21-79 years), from four national orienteering events, were analysed. The data
      for age and orienteering speed were log-transformed and regression analyses were
      conducted to determine the relationships between age and sex and orienteering
      speed. For comparison, data for the fastest Great Britain finisher in the 10,000
      m track and 10-km cross-country events for age groups 40-69 years at the World
      Masters Championships were also analysed. The results showed that, before the age
      of 40 years, there was no substantial slowing in orienteering speed for males
      (0.5-4.2% per decade) but a moderate decline (4.7-10.0% per decade) for females.
      After the age of 45 years, the orienteering speed of males and females slowed by
      13+/-2% and 16+/-4% per decade (mean +/- s), respectively, until around the age
      of 69, after which the deterioration was accentuated. The orienteering speed of
      the females was 81+/-4, 74+/-6 and 69+/-7% that of the males at ages 21, 45 and
      65 years, respectively. The magnitudes of the age-related slowing of orienteering
      speed and of the difference in orienteering speed between males and females aged
      45 years and over were greater than those reported for the other endurance
      running events. This may reflect the physical demands of running in orienteering
      terrain, tactical and cognitive aspects of the sport, or sociocultural aspects of
      the participating population.

PMID- 11311023
TI  - The evolution of physique in male rugby union players in the twentieth century.
AB  - Data on 1420 high-standard rugby union players measured between 1905 and 1999
      were collated to chart the evolution of body size and shape in rugby union
      football. Individual data were available for 843 players. Where only summary
      statistics were presented, Monte Carlo simulation was used to generate pseudo
      data. Anthropometric variables included height, body mass, body mass index (BMI)
      and somatotype where available. The rates of increase in body mass (2.6 kg per
      decade) and BMI (0.4 kg x m(-2) per decade) were well above those of the general
      population of young males. The increase in height (1.0 cm per decade) was
      comparable to the secular increase. The increases in body mass and BMI since 1975
      have been three to four times those between 1905 and 1975. Since 1975, players
      have been less endomorphic (-0.3 units per decade) and less ectomorphic (-0.4
      units per decade), but much more mesomorphic (+1.1 units per decade) than before.
      There is a close association between body size and success. Final ranking in the
      1999 World Cup showed significant correlations with the average mass of the
      squads.

PMID- 11311024
TI  - Muscle power patterns in the mid-acceleration phase of sprinting.
AB  - To assess the role of the lower limb joints in generating velocity in the mid
      acceleration phase of sprinting, muscle power patterns of the hip, knee and ankle
      were determined. Six male sprinters with a mean 100 m time of 10.75 s performed
      repeated maximal sprints along a 35 m indoor track. A complete stride across a
      force platform, positioned at approximately 14 m into the sprint, was video
      recorded for analysis. Smoothed coordinate data were obtained from manual
      digitization of (50 Hz) video images and were then interpolated to match the
      sampling rate of the recorded ground reaction force (1000 Hz). The moment at each
      joint was then calculated using inverse dynamics and multiplied by the angular
      velocity to determine the muscle power. The results showed a proximal-to-distal
      timing in the generation of peak extensor power during stance at the hip, the
      knee and then the ankle, with the plantar flexors producing the greatest peak
      power. Apart from a moderate power generation peak towards toe-off, knee power
      was negligible despite a large extensor moment throughout stance. The role of the
      knee thus appears to be one of maintaining the centre of mass height and enabling
      the power generated at the hip to be transferred to the ankle.

PMID- 11311025
TI  - Stability of psychometric questionnaires.
AB  - In 1999, Wilson and Batterham proposed a new approach to assessing the test
      retest stability of psychometric questionnaires. They recommended assessing the
      proportion of agreement - that is, the proportion of participants that record the
      same response to an item - using a test-retest design. They went on to use a
      bootstrapping technique to estimate the uncertainty of the proportion of
      agreement. The aims of this short communication are (1) to demonstrate that the
      sampling distribution of the proportion of agreement is well known (the binomial
      distribution), making the technique of 'bootstrapping' redundant, and (2) to
      suggest a much simpler, more sensitive method of assessing the stability of a
      psychometric questionnaire, based on the test-retest differences (within
      individuals) for each item. Adopting methods similar to Wilson and Batterham, 97
      sport students completed the Social Physique Anxiety Scale on two occasions. Test
      retest differences were calculated for each item. Our results show that the
      proportion of agreement ignores the nature of disagreement. Items 4 and 11 showed
      similar agreement (44.3% and 43.3% respectively), but 89 of the participants
      (91.8%) differed by just +/-1 point when responding to item 4, indicating a
      relatively stable item. In contrast, only 78 of the participants (80.4%) recorded
      a difference within +/- 1 point when responding to item 11, suggesting quite
      contrasting stability for the two items. We recommend that, when assessing the
      stability of self-report questionnaires using a 5-point scale, most participants
      (90%) should record test-retest differences within a reference value of +/- 1.

PMID- 11311026
TI  - Factors affecting the likelihood to engage in adequate physical activity to
      promote health.
AB  - The aim of this study was to assess the likelihood of individuals to participate
      in enough physical activity to promote fitness and, more conservatively, to
      accrue only health benefits. Sedentary (n = 883; 20.5%) and active (n = 1144;
      26.5%) groups were identified from the 1990 Allied Dunbar National Fitness Survey
      of English adults (n = 4316). The data were analysed using logistic regression.
      Participants were described using 20 variables identified from previous research,
      six of which made a significant contribution to the model (P < 0.05). The odds of
      being sedentary increased with age, self-perception of lifestyle problems, and
      lower scores on education, self-perception of motivation to exercise, perception
      of own participation in physical activity and recognition of exercising enough
      for health benefits. The odds of being active were associated with the opposite
      characteristics to those observed for sedentary behaviour. The extreme scores
      varied from individuals who may be 385 times more likely to be sedentary, to
      those who were 29 times more likely to be active, depending on scores on the
      selected variables. The results of this study provide a means to determine
      individual propensity to participate in adequate physical activity, and to
      identify those who may benefit most from health promotion campaigns.

PMID- 11311027
TI  - Reliability of power output measurements during repeated treadmill sprinting in
      rugby players.
AB  - The non-motorized treadmill system initially reported by Lakomy in 1984 has been
      used extensively to assess sprinting performance. However, there has been limited
      research into the reliability of power output measurement using such systems. The
      aim of this study was to design a system and protocol capable of measuring
      treadmill sprinting performance in rugby players and to assess the reliability of
      this system for measuring power output. Twenty-seven rugby players, all of whom
      were familiar with treadmill sprinting, performed three maximal 6 s sprints with
      2 min recovery between sprints, on two occasions 1 week apart. Both tests were
      performed on a non-motorized Woodway tramp treadmill, interfaced to a data
      acquisition system. There were no significant differences (P > 0.05) between
      power output for repeated trials on the same day (between trials) or for repeated
      trials on different days (between days). Limits of agreement for maximum average
      power (the average of 100 readings per second) were 4+/-98 and 30+/-157 W for
      between trials and between days, respectively. When reported as ratio limits of
      agreement, these were 1.07 (*/divided 1.12) and 1.03 (*/divided 1.16),
      respectively. The limits of agreement for maximum instantaneous power (the
      highest of 100 readings per second) were 51+/-464 and 105+/-588 W for between
      trials and between days, respectively. When reported as ratio limits of
      agreement, these were 1.02 (*/divided 1.20) and 1.04 (*/divided 1.21) for between
      trials and between days, respectively. The coefficients of variation for all
      measures of power output were less than 9.3%. Hence, the treadmill system and
      protocol developed in this study provide a reliable measure of power output for
      rugby players.

PMID- 11311028
TI  - Inhibition of return in children with perinatal brain injury.
AB  - Inhibition of return is a bias in attention that reduces the likelihood of
      returning attention to previously viewed locations. This attention bias develops
      during the first 6 months of life and is putatively mediated by midbrain
      structures. The present study evaluated the effects of perinatal lesions on the
      development of inhibition of return. Thirty-three children with perinatal injury
      resulting in spastic diplegic cerebral palsy were grouped based on magnetic
      resonance exams. Children with anterior (n = 5), posterior (n = 12), diffuse (n =
      8), or no apparent (n = 8) lesions were compared with a group of age-matched
      children without neurologic injury (n = 39) on an orienting task designed to
      elicit inhibition of return. Short-delay trials demonstrated grossly intact
      facilitation of attention for all groups. Long-delay trials that produced
      inhibition of return in the control and posterior injury groups indicated a
      disruption of inhibition of return in the groups with anterior and diffuse
      lesions. The findings are consistent with previous reports that anterior regions
      are important for the developing attention system, and that bilateral injury can
      result in unilateral disruption of visual attention.

PMID- 11311029
TI  - Working memory deficits associated with chronic fatigue syndrome.
AB  - Cognitive impairments are among the most frequently reported and least
      investigated components of the chronic fatigue syndrome (CFS). As part of a
      multifaceted study of the CFS, the present study investigated the cognitive
      functioning of chronic fatigue patients. The performance of 20 CFS patients was
      compared to that of controls (N = 20) on 4 tests of working memory (WM). Digit
      Span Forward was used to assess the storage capacity of WM. Multiple aspects of
      central executive functioning were assessed using several standard measures:
      Digit Span Backward, and Trails A and Trails B. More recently developed measures
      of WM were used to assess control of processing under temporal demands (working
      memory task) and resistance to interference (a sustained attention task).
      Deficits were restricted to more demanding tasks, requiring resistance to
      interference and efficient switching between processing routines. The overall
      results clearly implicate deficits in the control aspects of central executive
      function in CFS.

PMID- 11311030
TI  - Priming performance in Alzheimer's disease: the role of task sensitivity.
AB  - Studies examining implicit memory performance in Alzheimer's disease (AD) have
      yielded inconsistent findings, with these patients demonstrating impaired
      performance within some priming studies and intact performance within others. The
      present study examined the role of task sensitivity in detecting impaired priming
      in memory-impaired patients. Twelve healthy older adults and 12 AD patients were
      administered a picture fragment identification test. Task sensitivity was
      increased by employing stimulus cues expected to produce larger and more variable
      priming effects than obtained in previous studies. A simple comparison of priming
      scores revealed that the AD patients demonstrated significantly impaired priming
      relative to normal control participants. However, further analysis of priming in
      relation to certain stimulus characteristics revealed that AD patients often
      demonstrated impaired priming when overall priming effects were large but
      relatively intact priming when priming effects were small. These findings suggest
      that the prevention of ceiling effects in control participants may aid in the
      detection of impaired priming in patient populations.

PMID- 11311031
TI  - Interhemispheric Stroop effects in partial and complete agenesis of the corpus
      callosum.
AB  - Previous research had demonstrated diminished interhemispheric Stroop effects in
      individuals with agenesis of the corpus callosum (ACC), suggesting an important
      role for the callosum in interhemispheric color-word and color-patch
      interactions. However, this outcome rested on the results of only 1 ACC
      participant, who had normal intelligence and a minimum of other neuropathology.
      In the research reported herein, the role of the corpus callosum in
      interhemispheric Stroop interference and facilitation was investigated in 9
      individuals with complete or partial ACC and normal intelligence, and in non-ACC
      controls. Congruent, incongruent, or neutral stimulus pairs were presented either
      unilaterally (color-patch and color-word in the same visual field) or bilaterally
      (color-patch and color-word in different visual fields). Both unilateral and
      bilateral (interhemispheric) Stroop interference were found for both ACC and non
      ACC groups, with no significant difference in magnitude, indicating that
      extracallosal pathways are sufficient for mediating this phenomenon. It is
      suggested that the anterior commissure is a more likely candidate for the
      interhemispheric transmission of the semantic information resulting in Stroop
      interference.

PMID- 11311032
TI  - Improved memory functioning and frontal lobe maturation between childhood and
      adolescence: a structural MRI study.
AB  - Previous studies conducted by our group have provided evidence for age-related
      reductions in cortical thickness in dorsal frontal and parietal regions between
      childhood and adulthood, and gray matter volume increases of mesial temporal and
      anterior diencephalic structures. The purpose of this study was to describe
      neurobehavioral correlates of these brain maturational changes using morphometric
      analyses of brain magnetic resonance images (MRI) and two tests of cognitive
      abilities. Participants were 35 normal children roughly stratified by age (7 to
      16 years) and sex (20 boys and 15 girls) and frontal and mesial temporal regions
      were anatomically defined in each subjects' MRI data. The California Verbal
      Learning Test-Children's Version and the Rey-Osterrieth Complex Figure test were
      used as measures of verbal and visuospatial memory and organizational abilities.
      Analyses designed to show regionally specific relationships between the brain and
      behavioral measures revealed interesting results. Specifically, frontal lobe gray
      matter thinning was more strongly predictive of delayed verbal memory functioning
      than was the mesial temporal lobe gray matter volume, and this relationship did
      not appear to be mediated by factors indexed in chronological age. Similar, but
      less regionally specific relationships were observed for measures of visuospatial
      memory abilities and frontal lobe maturation. Functional imaging studies in the
      literature consistently report activation in frontal regions in adults during
      retrieval tasks. The relationship between frontal lobe maturation and delayed
      recall observed here may be reflective of the children's development towards the
      more adult-like frontal lobe function revealed in the functional imaging studies.

PMID- 11311033
TI  - "Expectation as etiology" versus "the good old days": postconcussion syndrome
      symptom reporting in athletes, headache sufferers, and depressed individuals.
AB  - The present study explored the explanatory power of Mittenberg's "expectation as
      etiology" theory for the persistence of postconcussion syndrome (PCS) complaints.
      One hundred forty-one participants completed a PCS symptom checklist under 2
      conditions. Normal controls, healthy athletes and depressed individuals reported
      current symptoms and symptoms expected following a hypothetical mild head injury.
      Head-injured athletes, chronic headache sufferers, and a 2nd sample of normal
      controls reported current symptoms and retrospective symptoms (prior to their
      injury/illness or from some point in the past). Depressed individuals reported
      more current symptoms than normal controls and healthy athletes, demonstrating
      that "PCS" symptoms are not specific to PCS. All groups expected more symptoms
      following mild head injury than currently experienced, supporting the idea that
      individuals expect negative consequences following head injury. However, healthy
      athletes expected fewer symptoms than normals or depressed individuals, possibly
      due to preexisting expectations for speedy recovery. Both head-injured athletes
      and headache sufferers reported more current symptoms than the past, but not at a
      rate lower than baseline of normal controls. Results suggest that the
      "expectation as etiology" hypothesis may be too specific, and that, following any
      negative event, people may attribute all symptoms to that negative event (the
      "good old days" hypothesis).

PMID- 11311034
TI  - A kinematic analysis of distractor interference effects during visually guided
      action in spatial neglect.
AB  - Patients with left spatial neglect following right hemisphere damage may show
      anomalies in ipsilesional-limb movements directed to targets on their affected
      side, in addition to their characteristic perceptual deficits. In this study we
      examined the extent to which visually guided movements made by neglect patients
      are susceptible to interference from concurrent visual distractors on the
      contralesional or ipsilesional side of a designated target. Eleven right
      hemisphere patients with visual neglect, plus 11 matched healthy controls,
      performed a double-step movement task upon a digitizing tablet, using their
      ipsilesional hand to respond. On each double-step trial the first component of
      the movement was cued to a common central target, whereas the second component
      was cued unpredictably to a target on either the contralesional or ipsilesional
      side. On separate trials lateral targets either appeared alone or together with a
      concurrent distractor in an homologous location in the opposite hemispace. In
      addition to being significantly slower and more error prone than controls,
      neglect patients also exhibited a number of interference effects from
      ipsilesional distractors. They often failed to move to left targets in the
      presence of a right-sided distractor, or else they moved to the distractor itself
      rather than to a contralesional target. The initial accelerative phase of their
      movements to contralesional targets tended to be interrupted prematurely, and
      they spent significantly more time in the terminal guidance phase of movements to
      contralesional targets in the presence of an ipsilesional distractor. In
      contrast, contralesional distractors had little effect on patients' movements to
      ipsilesional targets. We conclude that right hemisphere damage induces a
      competitive bias that favors actions to ipsilesional targets. This bias affects
      multiple stages of processing within the visuomotor system, from initial
      programming through to the final stages of terminal guidance.

PMID- 11311035
TI  - Self-monitoring enhances Wisconsin Card Sorting Test performance in patients with
      schizophrenia: performance is improved by simply asking patients to verbalize
      their sorting strategy.
AB  - Patients with schizophrenia have Wisconsin Card Sorting Test (WCST) deficits,
      which are commonly interpreted as reflecting frontal cortex-based executive
      dysfunction. One means of assessing the refractoriness of frontal-executive
      impairment is to utilize a training or modification strategy to improve WCST
      performance. In this study, 73 patients with schizophrenia were assigned to 1 of
      2 groups. Group 1 received the standard WCST instructions for 64 cards (Condition
      1). For the second 64-card deck, the patients were asked to verbalize the reason
      that they placed the card where they did after each sort (Condition 2). Group 2
      received this modified instruction 1st (Condition 1) and then the standard
      instructions for the second deck (Condition 2). A group of normal comparison
      participants was also tested using standard instructions alone. Group 2 committed
      significantly fewer perseverative responses than did Group 1. Furthermore, there
      was no significant difference between Group 2 (Condition 1) and the normal
      participants. Group 1's performance improved when patients were exposed to the
      modified instructions (Condition 2). Additionally, poor premorbid factors and
      disorganized symptoms were associated with decreased benefit from the modified
      instructions across both groups. Cumulatively, these data suggest that a simple
      instruction may enhance executive function and impact WCST performance in
      patients with schizophrenia.

PMID- 11311036
TI  - The effects of mesial temporal and cerebellar hypometabolism on learning and
      memory.
AB  - The effects of mesial temporal (MT) and cerebellar hypometabolism were studied
      using measures of verbal, visual and motor skill learning. Twelve patients with
      refractory temporal lobe epilepsy who showed asymmetrical mesial temporal lobe
      hypometabolism on [18F] fluoro-2-deoxy-glucose positron emission tomography (FDG
      PET) were given tests involving 4 consecutive learning trials and a 30-min
      delayed recall trial. Delayed recognition was also assessed for the words and
      designs, and skill transfer was evaluated for mirror drawing. Compared to 9
      normal control participants, patients with more marked MT hypometabolism on the
      left had impaired delayed recall of words and patients with more marked MT
      hypometabolism on the right showed impaired learning of novel designs, but normal
      retention over delay. Patients were not impaired in their mirror-drawing
      performance. The findings for MT hypometabolism correspond well to those obtained
      in other studies where patients have been classified on the basis of side of
      hippocampal atrophy or temporal lobe excision.

PMID- 11311037
TI  - Limitations of the Paced Auditory Serial Addition Test as a measure of working
      memory in patients with multiple sclerosis.
AB  - The Paced Auditory Serial Addition Test (PASAT) is a commonly used procedure that
      combines elements of both a working memory task and a test of information
      processing speed. Patients with multiple sclerosis (MS) have consistently been
      found to be impaired on this test and it has been recommended as a core outcome
      measure in clinical trials. The standard score for this task is the number of
      correct responses at each stimulus presentation rate but a concern has been
      raised that subjects may ignore some test items in order to chunk the information
      into manageable portions and avoid performing several cognitive tasks
      simultaneously. To account for this strategy, one can examine the proportion of
      correct responses that are consecutive (termed dyads), since such responses
      require that the task be performed according to the instructions. We compared a
      group of 35 mildly to moderately disabled MS patients and matched healthy
      controls on the PASAT. The MS patients made significantly fewer correct responses
      at the 2 slowest presentation rates (2.4, 2.0 s/digit) while their scores at
      faster rates (1.6, 1.2 s/digit) did not discriminate them from controls as well.
      Nevertheless, the MS patients' percentage of dyads was significantly lower than
      that of the control sample across all stimulus presentation rates. While our
      study supports the use of the PASAT as a test that distinguishes MS patients from
      healthy individuals, our results also illustrate problems that lie in the
      interpretation of this difference in performance. It appears that a chunking
      strategy may be common in the PASAT, particularly as task demands increase, and
      that this may mask actual performance differences. If so, the total correct
      response score alone is limited as a measure of working memory and information
      processing speed. More detailed analyses of PASAT performance, coupled with other
      measures of information processing, may help clarify the underlying cognitive
      deficits of MS patients.

PMID- 11311038
TI  - Cognitive and neurobehavioral functioning after mild versus moderate traumatic
      brain injury in older adults.
AB  - This study evaluated the early cognitive and neurobehavioral outcomes of older
      adults with mild versus moderate traumatic brain injury (TBI). Thirty-five
      patients who were age 50 years and older and sustained mild or moderate TBI were
      prospectively recruited from acute care hospitals. Patients were administered
      cognitive and neurobehavioral measures up to 2 months post-injury.
      Demographically comparable control participants received the same measures.
      Patients and controls did not have previous histories of substance abuse,
      neuropsychiatric disturbance, dementia, or neurologic illness. Moderate TBI
      patients performed significantly poorer than mild TBI patients and controls on
      most cognitive measures, whereas the mild patients performed comparably to
      controls. In contrast, both mild and moderate patients exhibited significantly
      greater depression and anxiety/somatic concern than controls. The results
      indicate that the classification of TBI as mild versus moderate is prognostically
      meaningful as applied to older adults. The findings extend previous
      investigations in young adults by demonstrating a relatively good cognitive
      outcome on objective measures, but subjective complaints after a single,
      uncomplicated mild TBI in older persons.

PMID- 11311039
TI  - Remote memory for public figures in Alzheimer's disease: relationships to
      regional cortical and limbic brain volumes.
AB  - This study examined the relationships between regional cortical and hippocampal
      brain volumes and components of remote memory (recall, recognition, sequencing,
      and photo naming of presidential candidates) in 13 individuals with Alzheimer's
      disease (AD). Recognition and sequencing of remote memory for public figures were
      associated with regional cortical volumes. Specifically, lower recognition and
      sequencing scores were associated with smaller parietal-occipital cortical
      volumes; poorer sequencing was also associated with smaller prefrontal cortical
      volumes. By contrast, poorer anterograde but not remote memory scores were
      correlated with smaller hippocampal volumes. Within the constraints of the brain
      regions measured, these findings highlight the importance of the posterior
      cortical areas for selective remote memory processes and provide support for the
      dissociation between cortically mediated remote memory and hippocampally mediated
      anterograde memory.

PMID- 11311040
TI  - The influence of viewing eye on pseudoneglect magnitude.
AB  - Various factors influence the degree of leftward error (pseudoneglect) that
      typifies the performance of normal individuals in line bisection tasks. This
      experiment reveals that the eye through which stimuli are viewed also exerts a
      modulating influence on spatial attention, as indexed by significant alterations
      in the magnitude of pseudoneglect. Using a forced-choice tachistoscopic line
      bisection protocol, 24 participants (12 male; 12 female) bisected horizontally
      oriented lines (22.6 degrees w x 0.39 degrees h) presented to central vision in 3
      conditions: left uniocular viewing (L), right uniocular viewing (R), and
      binocular viewing (B). Perceived line midpoint, a measure of bisection accuracy,
      deviated significantly leftward of veridical (p < .05) in all viewing conditions,
      confirming a tonic asymmetry of visuospatial attention in normal young observers.
      In addition, a significant influence of viewing condition was found (p < .05)
      where pseudoneglect was greatest in the L condition, followed by the B and R
      conditions, respectively. Analysis of the slopes of the psychometric functions
      revealed significantly greater bisection precision in the binocular versus
      uniocular viewing conditions (p < .05). The results are interpreted to suggest
      that phasic effects on spatial attention can be produced by uniocular viewing via
      asymmetric retinotectal projections. The results are consistent with activation
      orientation theories of attentional asymmetry.

PMID- 11311041
TI  - Cellular and subcellular patterns of expression of bFGF and CNTF in the normal
      and light stressed adult rat retina.
AB  - This study compared the distributions in the normal and light stressed rat retina
      of the neuroprotective factors bFGF (basic fibroblast growth factor) and CNTF
      (ciliary neurotrophic factor). Albino Sprague-Dawley rats were raised in cyclic
      light and some were exposed to bright continuous light for 48 hr, to induce light
      damage of photoreceptors. Their retinas were prepared as cryosections,
      immunolabelled with antibodies to bFGF and CNTF and analysed by confocal
      microscopy. Both factors were prominent in macroglial cells (astrocytes, Muller
      cells) and the retinal pigment epithelium (RPE). In the somas of these cells the
      distributions of the two factors were complementary, with bFGF concentrated in
      the nuclei and CNTF in the cytoplasm. Both factors were distributed along the
      processes of macroglial cells, in granular form. CNTF was not detected in
      neurones, but bFGF was consistently present in the cytoplasm of ganglion cell
      somas and, in regions of retina subject to stress, in the cytoplasm of
      photoreceptors. bFGF was not detected in the nuclei or processes of neurones. In
      retina stressed by light exposure or proximity to the anterior edge of the
      retina, the levels of bFGF and CNTF were up-regulated, without major changes in
      localization. Macroglial cells (Muller cells, astrocytes) play a major role in
      distributing bFGF and CNTF throughout the retina. The different localizations of
      the two factors within the somas of macroglial, RPE and photoreceptor cells,
      suggest that their protective actions are exerted by distinctive mechanisms.

PMID- 11311042
TI  - Spectrum of mutations in USH2A in British patients with Usher syndrome type II.
AB  - Usher syndrome (USH) is a combination of a progressive pigmentary retinopathy,
      indistinguishable from retinitis pigmentosa, and some degree of sensorineural
      hearing loss. USH can be subdivided in Usher type I (USHI), type II (USHII) and
      type III (USHIII), all of which are inherited as autosomal recessive traits. The
      three subtypes are genetically heterogeneous, with six loci so far identified for
      USHI, three for USHII and only one for USHIII. Mutations in a novel gene, USH2A,
      encoding the protein usherin, have recently been shown to be associated with
      USHII. The gene encodes a protein with partial sequence homology to both laminin
      epidermal growth factor and fibronectin motifs. We analysed 35 British and one
      Pakistani Usher type II families with at least one affected member, for sequence
      changes in the 20 translated exons of the USH2A gene, using heteroduplex analysis
      and sequencing. Probable disease-causing mutations in USH2A were identified in 15
      of 36 (41.7%) Usher II families. The most frequently encountered mutation (11/15
      families or 11/18 mutated alleles) was del2299G in exon 13, resulting in a
      frameshift and premature stop codon. Other mutations include insertions and point
      mutations, of which two are previously unreported. Five different polymorphisms
      were also detected. Our results indicate that mutations in this gene are
      responsible for disease in a large proportion of British Usher type II patients.
      Moreover, if screening for mutations in USH2A is considered, it is sensible to
      screen for the del2299G mutation first.

PMID- 11311043
TI  - The epidermal growth factor receptor (EGFR): role in corneal wound healing and
      homeostasis.
AB  - To evaluate the role of the epidermal growth factor receptor (EGFR) in corneal
      epithelial wound healing, the effect of an EGFR inhibitor on epithelial cell
      proliferation and cell stratification during wound healing was investigated. From
      3 days prior to wounding until wound healing was complete, rats were systemically
      treated with either an EGFR tyrosine kinase inhibitor (ZD1839) at 40 mg kg(-1)
      day(-1)or 80 mg kg(-1) day(-1), or with vehicle only (control). A single corneal
      wound was made in the center of 66 rat corneas, using a 6.0 mm glass tube wrapped
      in tissue paper soaked in n-heptanol. Subsequently, each wound was photographed
      and measured by a computer-assisted digitizer every 12 hr. To determine the
      number of cells in S phase, entire corneas were labelled with (3)H-thymidine and
      subjected to autoradiography at 0, 12, 24 and 48 hr after wounding. Epithelial
      thickness was also measured at these time points by microscopy. Epithelial wound
      healing was significantly and dose-dependently delayed following administration
      of ZD1839. At 24 hr after wounding, the number of S-phase cells in the limbal
      corneal epithelium was significantly lower in both the treated groups compared
      with the control group (P < 0.05). In the cornea before wounding (0 hr) and at 48
      hr post-wounding, epithelial thickness was also significantly less in treated
      rats compared with controls (P < 0.05). These results indicate that EGFR
      inhibition affects epithelial cell proliferation and stratification during
      corneal epithelial wound healing and may play a role in maintaining normal
      corneal epithelial thickness.

PMID- 11311044
TI  - Identification and localization of acid-base transporters in the conjunctival
      epithelium.
AB  - Acid-base transporters of rabbit and porcine conjunctival epithelia were
      identified and localized with immunoblotting and immunohistochemical techniques
      using specific antibodies against carriers commonly found in epithelia, i.e. the
      Cl(-)/HCO3(-)exchanger (AE2), Na(+)/H(+) exchanger (NHE-1, -2, -3) and the
      electrogenic Na(+)-(n)HCO3(-) cotransporter (NBC). Western blot analysis
      demonstrated that anti-AE2 reacted with an approximate 170 kDa protein in both
      rabbit and pig cell membranes prepared from separately isolated bulbar and
      palpebral conjunctivae. NHE1 was similarly identified in these distinct
      conjunctival regions but results with anti-NBC were ambiguous. Histochemical
      examinations indicated that the AE2 and NHE1 proteins reside on the basolateral
      surfaces of the plasma membrane throughout the multilayered tissue. The
      immunostaining of porcine cryosections for AE2 and rabbit sections for NHE1 was
      specific, because of its abolishment following either pre-absorption with the
      corresponding peptide or omission of the primary antibody. Screening with anti
      NBC produced weak staining of the sections that appeared to be non-specific. For
      confirmation of these results, the acid-base transporters present in rabbit cell
      cultures of conjunctival epithelia were ascertained from the changes in
      intracellular pH (pH(i)) evoked upon sequential superfusion with media of altered
      composition. This approach readily obtained Na(+)- and Cl(-)-dependent
      pH(i)effects consistent with the existence of Cl(-)/HCO3(-) and
      Na(+)/H(+)exchange activities. Evidence for the presence of NBC could not be
      acquired, thereby substantiating the observations from the immunodetection
      techniques. The identity and location of the antiporters that were found
      suggested that these elements could contribute to transcellular Cl(-)transport in
      the basolateral-to-apical direction. To test this possibility, the effects of AE
      and/or NHE inhibition were determined on the bumetanide-insensitive Cl(-)
      dependent short-circuit current across rabbit conjunctivae freshly isolated in
      Ussing-type chambers. These experiments revealed that such current is indeed
      sustained by the antiporters. Results with acetazolamide further suggested that
      the contribution of the acid-base transporters towards transepithelial Cl(
      )secretion is variable and dependent upon individual rates of metabolic
      CO(2)production. Overall, the present study provides an initial identification of
      the acid-base transporters present in the conjunctiva. Besides their likely role
      in intracellular pH regulation, the parallel, basolateral expression of AE2 and
      NHE1 indicates that these elements do not directly contribute to the pH of the
      tear film but may complement the Na(+)-2Cl(-)-K(+)cotransporter in effectuating
      Cl(-)secretion.

PMID- 11311045
TI  - The effect of aging on glutathione peroxidase-i knockout mice-resistance of the
      lens to oxidative stress.
AB  - Populations of control, C, and glutathione peroxidase-1 (GPx-1) knockout mice, K,
      were studied over a period of 2 years. No significant difference was observed
      between the C and K populations with respect to longevity, vitality, weight, lens
      biochemistry or morphology based on light and electron microscopy. It was
      concluded that under normal animal room barrier facilities, GPx-1 is not
      required. Furthermore, C and K lenses placed in organ culture and observed over a
      24 hr period were indistinguishable. Organ cultured C lenses degraded medium
      H(2)O(2)levels at only a slightly greater rate than K lenses and this did not
      appear to change with age. However, tertiary butyl hydroperoxide (TBHP) was
      degraded less effectively by K lenses and this deficiency increased with age. No
      indication of change in redox non-protein SH (equivalent to GSH) status was
      observed between C and K whole lenses or epithelial cell fractions. With
      H(2)O(2)stress, the drop in C and K non-protein SH was comparable and there was
      little change with age. Examination of the impact of photochemical stress with
      1.5 microM riboflavin and 4% O(2)upon choline transport indicated considerable
      damage with both C and K lenses, but little difference between the two
      populations until 1 or 2 years of age when the K lenses appear more vulnerable.
      With TBHP, the detrimental effect on the K lenses is greater and is observed
      earlier than with photochemical stress suggesting that the K lens membrane
      function is more susceptible to phospholipid hydroperoxide stress than are C
      lenses. Light and electron microscopy of the oxidative stressed lenses indicates
      significant damage which was generally somewhat greater in the K lenses. TBHP was
      a more potent oxidant than photochemically generated oxidants particularly at the
      anterior pole. The overall results suggest that under normal conditions, at any
      age, the lens does not require the presence of GPx-1 but depending on the type of
      oxidative stress, the enzyme may significantly contribute to its defense and this
      dependency may increase with age.

PMID- 11311046
TI  - Transient down-regulation of NMDA receptor subunit gene expression in the rat
      retina following NMDA-induced neurotoxicity is attenuated in the presence of the
      non-competitive NMDA receptor antagonist MK-801.
AB  - Excitotoxic challenge has been thought to directly target NMDA-receptive neurons
      to undergo cell death. Recent evidence suggests that NMDA induced cell death is a
      selective process and that the specificity may be determined by the subunit
      composition of the NMDA receptor. Using a rat retinal model, we examined the
      effects of NMDA induced neurotoxicity on the regulation of NMDA receptor subunit
      gene and protein expression levels to determine if excitotoxic challenge
      preferentially regulates one or more of the NMDA receptor subunits. Following
      NMDA insult, the mRNA levels for NR1(com ), NR2A, NR2B and, to a lesser extent,
      the NR2C subunit were substantially reduced within 24 hr post-treatment (PT), and
      remained depressed for up to 48 hr. Levels for NR2D, although initially
      suppressed as early as 6 hr-PT, were least affected by NMDA insult and showed
      almost full recovery by 48 hr. By 10 days, the levels of gene expression for all
      five subunits recovered to levels that were indistinguishable from sham treated
      and untreated retinas. Co-administration of MK-801 with NMDA suppressed the
      effects of NMDA-induced down-regulation of all five genes. Protein levels for
      NR1(com ), NR2A and NR2B were also monitored at select time points following NMDA
      insult. By 2 days-PT, protein levels for the three subunits were dramatically
      reduced. By day 10, the levels of protein expression for NR1(com)and NR2B
      remained suppressed despite the rise in gene expression for these two subunits,
      whereas protein for NR2A showed a substantial rise in expression. Of the five
      genes assayed, NR2A and NR2B showed the greatest reduction in expression
      following NMDA treatment, suggesting that one or both of these subunit may signal
      events leading to neuronal cell death in the retina. Conversely, gene expression
      of the NR2D subunit was least affected by NMDA exposure. In view of the evidence
      that the NR2D subunit is expressed by rod bipolar cells in the rat and that these
      neurons do not die following NMDA insult, it appears that inclusion of this
      subunit into functional receptors may provide protection against NMDA-induced
      cell death. Although the significance of the transient down-regulation of four
      out of the five NMDA receptor subunits is still not fully understood, the
      recovery of expression of these genes by day 10-PT indicates that not all of the
      NMDA receptive neurons are susceptible to NMDA-induced cell death. The
      preferential down-regulation of the NR2A and NR2B receptor subunits may implicate
      these subunits as key players in mediating the excitotoxic signal in the retina
      and possibly elsewhere in the brain.

PMID- 11311047
TI  - Mechanism of asparagine deamidation during human senile cataractogenesis.
AB  - Previous studies have demonstrated that asparagine-143 of gammaS crystallin is
      preferentially deamidated in human cataractous lenses. A possible mechanism of
      nonenzymatic deamidation involves the initial formation of L -succinimidyl and D 
      succinimidyl intermediates, followed by ring cleavage and production of the
      respective L - and D - forms of beta-aspartate and alpha-aspartate. To determine
      if this mechanism occurs during cataractogenesis of the human lens, synthetic
      peptide standards together with reverse phase HPLC were used to purify and
      quantitate tryptic peptides from cataractous lenses that contained the beta
      aspartate and alpha-aspartate forms of residue 143. For all lenses analysed, the
      ratios of beta-aspartate/alpha-aspartate produced were consistent with a
      mechanism of deamidation involving succinimide intermediates. Surprisingly, the D
      / L ratios for all beta- and alpha-aspartates produced were very low, suggesting
      that the mechanism of deamidation preferentially involves the L -succinimidyl
      intermediate, with formation of the D -succinimidyl intermediate almost
      completely blocked by steric hindrance. Together, the results demonstrate that
      deamidation of asparagine-143 from gammaS crystallin of different human cataracts
      undergoes the same mechanism, which due to higher ordered structure of the native
      protein, results in the preferential production of one of two possible
      succinimidyl intermediates.

PMID- 11311048
TI  - Transcriptional up-regulation of the protooncogenes c-fos and c-jun following
      vitreous removal and short-term in vitro culture of bovine lenses.
AB  - Chemical (mainly oxidative) and mechanical (anterior capsule injury) stresses
      have been reported to up-regulate the expression of the protooncogenes c-fos and
      c-jun in the lens. Another potentially stressful, yet largely unexplored
      condition, inherent to all experiments requiring the in vitro culturing of
      isolated lenses, is vitreous removal. Based on the results of an extensive RNA
      gel blot analysis conducted on epithelial/capsule preparations isolated from calf
      lenses dissected and cultured under different conditions, we show, here, that
      lens isolation and short-term culture (1-2.5 hr, without any significant GSH
      depletion) result in a strong and time-dependent up-regulation of the c-jun and c
      fos mRNAs. This response, which relies on transcriptional protooncogene
      activation and is more intense for c-fos than for c-jun, is in part prevented by
      the preservation of the lens-vitreous contact, but not by the culture of vitreous
      stripped lenses on a vitreous bed. Supplementation of the culture medium with the
      antioxidant N -acetyl-cysteine slightly reduced the c-jun, but not the c-fos
      response. Protooncogene up-regulation thus appears to be mainly determined by the
      disruption of critical lens-vitreous interactions. Since this response takes
      place in the epithelial cells, these data also point to the existence of a
      communication mechanism whereby a posteriorly applied mechanical stress is
      transmitted to, and perceived by, the anterior lens surface.

PMID- 11311049
TI  - Reliability assessment of a rod photoreceptor outer segment grading system.
AB  - The purpose of this study was to assess the reliability of a rod photoreceptor
      outer segment (PR-OS) grading system based on the analysis of 1 microm thick
      retinal sections obtained from Xenopus laevis whole-eye organ cultures. Digitally
      captured images, representative of the entire spectrum of rod PR-OS organization
      levels, were selected and coded numerically. A total of 102 individual rod PR-OS
      profiles were graded according to a six-step classification scheme based on the
      percentage of rod PR-OS membrane organization. Unweighted (exact agreement) and
      weighted kappa (kappa) coefficients (for use with ordered categorical rating
      scales) were calculated. Differences between kappa coefficients were tested for
      by chi-square analysis. To investigate the intra- and inter-rater variability and
      the possible presence of an interaction of the measurements with time, a repeated
      measures analysis of variance was performed. The overall unweighted and weighted
      intra-rater kappa coefficients were 0.78 and 0.92, respectively. The overall
      unweighted and weighted inter-rater kappa coefficients were 0.73 and 0.90,
      respectively. There was no significant difference between raters or between first
      and second reading, nor was interaction between raters and time of rating
      documented. Individual kappa coefficients were equivalent both between raters and
      between sessions. Intra- and inter-rater agreement was within one step in 100% of
      cases. The estimated values of the kappa coefficients are consistent with a good
      to excellent degree of reliability and reproducibility of this rod PR-OS grading
      system. This system will be useful in the assessment of rod PR-OS morphology in
      studies of photoreceptor physiology and pathology.

PMID- 11311050
TI  - Effects of prostaglandin F(2alpha)and carbachol on MAP kinases, cytosolic
      phospholipase A(2)and arachidonic acid release in cat iris sphincter smooth
      muscle cells.
AB  - The signal transduction pathways initiated by Ca(2+)-mobilizing agonists, such as
      prostaglandin F(2alpha)(PGF(2alpha)) and carbachol (CCh), leading to activation
      of cytosolic phospholipase A(2)(cPLA(2)) and arachidonic acid (AA) release in a
      wide variety of tissues remain obscure. To further define the role of protein
      kinases in receptor mediated stimulation of cPLA(2)and consequently AA release we
      have investigated the role of mitogen-activated protein (MAP) kinases and protein
      kinase C (PKC) in PGF(2alpha)- and CCh-induced cPLA(2)phosphorylation and AA
      release in cat iris sphincter smooth muscle (CISM) cells. The cells were
      prelabeled with [(3)H]AA for 24 hr and incubated in the absence or presence of
      the agonist for 5-10 min as indicated. MAP kinases activities and
      cPLA(2)phosphorylation were determined in immunoprecipitates obtained by using
      anti-p38 MAP kinase and anti-cPLA(2)antibodies. We found that: (a) PGF(2alpha)and
      CCh increased p38 MAP kinase activity by 197 and 215%, respectively, and
      increased p42/p44 MAP kinase activity by 200 and 125%, respectively. (b)
      SB202190, a p38 MAP kinase specific inhibitor, inhibited PGF(2alpha)- and CCh
      induced cPLA(2)phosphorylation by 92 and 85%, respectively, and AA release by 62
      and 78%, respectively. (c) PD98059, a p42/p44 MAP kinase inhibitor, inhibited CCh
      induced cPLA(2)phosphorylation by 70% and AA release by 71%, but had no effect on
      that of PGF(2alpha). (d) Inhibition of PKC activity by RO 31-8220 inhibited both
      PGF(2alpha)- and CCh-stimulation of p38 MAP kinase, p42/p44 MAP kinases and
      cPLA(2)phosphorylation. We conclude from these results that in CISM cells
      PGF(2alpha)-induced cPLA(2)phosphorylation and AA release is mediated through p38
      MAP kinase, but not through p42/p44 MAP kinases, whereas that of CCh is mediated
      through both p38 MAP kinase and p42/p44 MAP kinases. These effects of
      PGF(2alpha)and CCh are regulated by the MAP kinases in a PKC-dependent manner.
      Studies aimed at elucidating the role of protein kinases in the coupling
      mechanism between the activation of PGF(2alpha)and muscarinic receptors, and the
      stimulation of cPLA(2)and AA release in the smooth muscles of the iris-ciliary
      body will provide important information about the role of protein kinases
      signaling pathways in smooth muscle function, as well as about the mechanism of
      the intraocular pressure-lowering effects of PGF(2alpha)and its analog,
      latanoprost, in glaucoma therapy.

PMID- 11311051
TI  - Development of normal and injury-induced gene expression of aFGF, bFGF, CNTF,
      BDNF, GFAP and IGF-I in the rat retina.
AB  - Focal mechanical injury to the retina substantially increases basic fibroblast
      growth factor (bFGF) and ciliary neurotrophic factor (CNTF) mRNA expression,
      accompanied by a transient increase in FGFR-1 mRNA, and this response is thought
      to protect photoreceptors near the injury site from inherited and light-induced
      retinal degenerations. We have now examined retinal gene expression of the
      principal survival factors involved in the response to injury in normal rats as a
      function of postnatal age both in normal and injured retinas. Sprague-Dawley rats
      were injured in one eye by needle incision through the retina at postnatal day
      (P) 10, 22, 35, 60, 90, 120 and 180. The other eye was uninjured and served as
      the control. Retinas were taken 1 day post-injury. Northern blot analysis was
      performed to determine the mRNA expression of the following factors and
      receptors: bFGF and acidic fibroblast growth factors (aFGF) and FGF receptor-1
      (FGFR-1); CNTF and CNTF receptor alpha (CNTFR-alpha); brain-derived neurotrophic
      factor (BDNF) and its receptor trk B; and insulin-like growth factor-I (IGF-I)
      and IGF-I receptor (IGF-IR); glial fibrillary acidic protein (GFAP) and opsin. In
      the uninjured control eyes, mRNA expression of most of the factors increased with
      postnatal age, with little expression at P10 and maximal expression levels
      reached at P22 (opsin), P35 (aFGF), P60 (BDNF) or P90 (bFGF, FGFR-1, CNTF and
      GFAP). In contrast, IGF-1 mRNA rapidly decreased from a high level of expression
      at P10 to about 55% of that level by P22, reaching a stable 45-50% of the P10
      level at P35 and thereafter. The response to injury of bFGF, FGFR-1, CNTF and
      GFAP mRNAs increased with postnatal age. Unexpectedly, only minimal increases in
      bFGF, FGFR-1, CNTF and GFAP over those seen in the control eyes were observed
      before P35. Thereafter, the increase of bFGF mRNA after injury reached a maximum
      of three-fold at P60, maintained this level to P120, and slightly decreased to
      2.5-fold by P180. Expression of FGFR-1 mRNA showed a maximum increase of 2.6-fold
      at P90. Expression of CNTF and GFAP mRNAs followed a time course similar to that
      of bFGF. Mechanical injury did not alter the mRNA levels of aFGF, BDNF, IGF-I,
      and receptors, CNTFR-alpha, trk B and IGF-IR. These data show that the response
      to injury is minimal at early postnatal ages but increases with age and peaks at
      P60-90 for most potential survival factors.

PMID- 11311052
TI  - Thymosin beta 4 promotes corneal wound healing and modulates inflammatory
      mediators in vivo.

PMID- 11311053
TI  - Property-based design: optimization of drug absorption and pharmacokinetics.

PMID- 11311054
TI  - Indenopyrazoles as novel cyclin dependent kinase (CDK) inhibitors.

PMID- 11311055
TI  - Atropisomeric derivatives of 2',6'-disubstituted (R)-11-phenylaporphine:
      selective serotonin 5-HT(7) receptor antagonists.

PMID- 11311056
TI  - Novel peptide conjugates for tumor-specific chemotherapy.
AB  - One of the major problems in cancer chemotherapy are the severe side effects that
      limit the dose of the anticancer drugs because of their unselectivity for tumor
      versus normal cells. In the present work, we show that coupling of anthracyclines
      to peptides is a promising approach to obtain selectivity. The peptide-drug
      conjugate was designed to bind to specific receptors expressed on the tumor cells
      with subsequent internalization of the ligand-receptor complex. Neuropeptide Y
      (NPY), a 36-amino acid peptide of the pancreatic polypeptide family, was chosen
      as model peptide because NPY receptors are overexpressed in a number of
      neuroblastoma tumors and the thereof derived cell lines. Daunorubicin and
      doxorubicin, two widely used antineoplastic agents in tumor therapy, were
      covalently linked to NPY via two spacers that differ in stability: an acid
      sensitive hydrazone bond at the 13-keto position of daunorubicin and a stable
      amide bond at the 3'-amino position of daunorubicin and doxorubicin. Receptor
      binding of these three conjugates ([C(15)]-NPY-Dauno-HYD, [C(15)]-NPY-Dauno-MBS,
      and [C(15)]-NPY-Doxo-MBS) was determined at the human neuroblastoma cell line SK
      N-MC, which selectively expresses the NPY Y(1) receptor subtype, and cytotoxic
      activity was evaluated using a XTT-based colorimetric cellular cytotoxicity
      assay. The different conjugates were able to bind to the receptor with affinities
      ranging from 25 to 51 nM, but only the compound containing the acid-sensitive
      bond ([C(15)]-NPY-Dauno-HYD) showed cytotoxic activity comparable to the free
      daunorubicin. This cytotoxicity is Y(1) receptor-mediated as shown in blocking
      studies with BIBP 3226, because tumor cells that do not express NPY receptors
      were sensitive to free daunorubicin, but not to the peptide-drug conjugate. The
      intracellular distribution was investigated by confocal laser scanning
      microscopy. We found evidence that the active conjugate [C(15)]-NPY-Dauno-HYD
      releases daunorubicin, which is localized close to the nucleus, whereas the
      inactive conjugate [C(15)]-NPY-Dauno-MBS is distributed distantly from the
      nucleus and does not seem to release the drug within the cell.

PMID- 11311057
TI  - Structure-based approach for the discovery of bis-benzamidines as novel
      inhibitors of matriptase.
AB  - Matriptase, a trypsin-like serine protease, which may be involved in tissue
      remodeling, cancer invasion, and metastasis. Potent and selective matriptase
      inhibitors not only would be useful pharmacological tools for further elucidation
      of the role of matriptase in these processes but also could have therapeutic
      potential for the treatment and/or prevention of cancers. We report herein the
      structure-based approach for the discovery of bis-benzamidines as a novel class
      of potent matriptase inhibitors. The lead compound, hexamidine (1), inhibits not
      only the proteolytic activity of matriptase, (K(i) = 924 nM) but also of thrombin
      K(i) = 224 nM). By testing several available analogues, we identified a new
      analogue (7) that has a K(i) = 208 nM against matriptase and has only weak
      inhibitory activity against thrombin (K(i) = 2670 nM), thus displaying a 13-fold
      selectivity toward matriptase. Our results demonstrated that structure-based
      database screening is effective in the discovery of matriptase inhibitors and
      that bis-benzamidines represent a class of promising matriptase inhibitors that
      can be used for further drug design studies. Finally, our study suggested that
      there is sufficient structural differences between matriptase and its closely
      related serine proteases, such as thrombin, for the design of potent and
      selective matriptase inhibitors.

PMID- 11311058
TI  - Short peptides with induced beta-turn inhibit the interaction between HIV-1 gp120
      and CD4.
AB  - To identify novel peptides that inhibit the interaction between human
      immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 and CD4, we
      constructed a targeted phage-displayed peptide library in which phenylalanine and
      proline were fixed at the fourth and sixth positions, respectively, because Phe43
      and the adjacent beta-turn of CD4 are critical for interaction with gp120. Two
      synthetic peptides were selected after three rounds of biopanning against gp120,
      and one of them, G1 peptide (ARQPSFDLQCGF), exhibited specific inhibition of the
      interaction between gp120 and CD4 with an IC(50) of about 50 microM. Structural
      analysis using NMR demonstrated that G1 peptide forms a compact cyclic structure
      similar to the CD4 region interacting with gp120. Two derivatives of G1 peptide,
      a linear hexameric peptide (G1-6) and a cyclic nonameric peptide (G1-c), were
      synthesized based on the structure of the G1 peptide. Interestingly, they showed
      higher inhibitory activities than did G1 peptide with IC(50)'s of 6 and 1 microM,
      respectively. Thus, this study might provide a new insight into the development
      of anti-HIV-1 inhibitors.

PMID- 11311060
TI  - Development of potent truncated glucagon antagonists.
AB  - In pursuit of truncated glucagon analogues that can interact with the glucagon
      receptor with substantial binding affinity, 23 truncated glucagon analogues have
      been designed and synthesized. These truncated analogues consist of several
      fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally
      constrained analogues containing the sequence of the middle region of glucagon (5
      15), and truncated analogues containing the sequence of the C-terminal region (16
      23). Biological assays of these analogues showed that the truncated glucagon
      analogues with the sequence of the C-terminal region possess significantly better
      binding affinity compared to the truncated analogues with the sequence of the
      middle region, and these analogues (17-23) demonstrated potent antagonistic
      activity (pA(2) values between 6.5 and 7.5). On the basis of these results, it
      can be suggested that glucagon interacts with its receptor with two hydrophobic
      patches located in the middle and the C-terminal regions of glucagon, and both
      hydrophobic patches are necessary for significant receptor recognition. These two
      hydrophobic binding motifs, located in two different regions of glucagon, appear
      to be the reason why the earlier attempts to obtain truncated analogues with good
      binding affinity did not result in any success. Long peptide hormones such as
      glucagon seem to require more than one binding pocket on the receptors for
      maximal interaction.

PMID- 11311059
TI  - Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin
      pyrophosphokinase: synthesis and biochemical and crystallographic studies.
AB  - 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer
      of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), leading to
      the biosynthesis of folate cofactors. Like other enzymes in the folate pathway,
      HPPK is an ideal target for the development of antimicrobial agents because the
      enzyme is essential for microorganisms but is absent from human and animals.
      Three bisubstrate analogues have been synthesized for HPPK and characterized by
      biochemical and X-ray crystallographic analyses. All three bisubstrate analogues
      consist of a pterin, an adenosine moiety, and a link composed of 2-4 phosphoryl
      groups. P(1)-(6-Hydroxymethylpterin)-P(2)-(5'-adenosyl)diphosphate (HP(2)A, 5)
      shows little affinity and inhibitory activity for E. coli HPPK. P(1)-(6
      Hydroxymethylpterin)-P(3)-(5'-adenosyl)triphosphate (HP(3)A, 6) shows moderate
      affinity and inhibitory activity with K(d) = 4.25 microM in the presence of
      Mg(2+) and IC(50) = 1.27 microM. P(1)-(6-Hydroxymethylpterin)-P(4)-(5'
      adenosyl)tetraphosphate (HP(4)A, 7) shows the highest affinity and inhibitory
      activity with K(d) = 0.47 microM in the presence of Mg(2+) and IC(50) = 0.44
      microM. The affinity of MgHP(4)A for HPPK is approximately 116 and 76 times
      higher than that of MgADP and 6-hydroxymethylpterin, respectively. The crystal
      structure of HPPK in complex with 7 (HPPK.MgHP(4)A) has been determined at 1.85 A
      resolution with a crystallographic R factor of 0.185. The crystal structure shows
      that 7 occupies both HP- and ATP-binding sites and induces significant
      conformational changes in HPPK. The biochemical and structural studies of the
      bisubstrate analogues indicate that the bisubstrate analogue approach can produce
      more potent inhibitors for HPPK and the minimum length of the link for a
      bisubstrate analogue is approximately 7 A.

PMID- 11311061
TI  - Azepanone-based inhibitors of human and rat cathepsin K.
AB  - The synthesis, in vitro activities, and pharmacokinetics of a series of azepanone
      based inhibitors of the cysteine protease cathepsin K (EC 3.4.22.38) are
      described. These compounds show improved configurational stability of the C-4
      diastereomeric center relative to the previously published five- and six-membered
      ring ketone-based inhibitor series. Studies in this series have led to the
      identification of 20, a potent, selective inhibitor of human cathepsin K (K(i) =
      0.16 nM) as well as 24, a potent inhibitor of both human (K(i) = 0.0048 nM) and
      rat (K(i,app) = 4.8 nM) cathepsin K. Small-molecule X-ray crystallographic
      analysis of 20 established the C-4 S stereochemistry as being critical for potent
      inhibition and that unbound 20 adopted the expected equatorial conformation for
      the C-4 substituent. Molecular modeling studies predicted the higher energy axial
      orientation at C-4 of 20 when bound within the active site of cathepsin K, a
      feature subsequently confirmed by X-ray crystallography. Pharmacokinetic studies
      in the rat show 20 to be 42% orally bioavailable. Comparison of the transport of
      the cyclic and acyclic analogues through CaCo-2 cells suggests that oral
      bioavailability of the acyclic derivatives is limited by a P-glycoprotein
      mediated efflux mechanism. It is concluded that the introduction of a
      conformational constraint has served the dual purpose of increasing inhibitor
      potency by locking in a bioactive conformation as well as locking out available
      conformations which may serve as substrates for enzyme systems that limit oral
      bioavailability.

PMID- 11311062
TI  - Novel seco cyclopropa[c]pyrrolo[3,2-e]indole bisalkylators bearing a 3,3'
      arylenebisacryloyl group as a linker.
AB  - We synthesized the novel seco cyclopropa[c]pyrrolo[3,2-e]indole (CPI)
      bisalkylators and evaluated their antitumor activity. Among these derivatives,
      11a (AT-760), in which the two seco 3-methoxycarbonyl-2-trifluoromethyl CPI
      (MCTFCPI) moieties are connected with a 3,3'-(1,4-phenylene)bisacryloyl group,
      was found to exhibit more potent cytotoxicity and antitumor activity against
      HeLaS3 human uterine cervix carcinoma cells and Colon 26 adenocarcinoma cells,
      respectively, than 8 (bizelesin, U-77,779). It also appeared that compound 11a
      exhibits improved in vivo efficacy in the human colon CX-1 model when compared to
      either compound 8 or mitomycin C (MMC). Efficacious doses for 11a were found to
      be 2-fold lower than those for 8.

PMID- 11311063
TI  - Dicationic bis(9-methylphenazine-1-carboxamides): relationships between
      biological activity and linker chain structure for a series of potent
      topoisomerase targeted anticancer drugs.
AB  - Bis(9-methylphenazine-1-carboxamides) joined by a variety of dicationic
      (CH(2))(n)()NR(CH(2))(m)NR(CH(2))(n) linkers of varying length (carboxamide N-N
      distances from 11.0 to 18.4 A) and rigidity were prepared by reaction of 9
      methylphenazine-1-carboxylic acid imidazolide with the appropriate polyamines.
      The compounds were evaluated for growth inhibitory properties in P388 leukemia,
      Lewis lung carcinoma, and wild-type (JL(C)) and mutant (JL(A) and JL(D)) forms of
      human Jurkat leukemia with low levels of topoisomerase II (topo II). The
      compounds all had IC(50) ratios of <1 in the resistant Jurkat lines, consistent
      with topo II inhibition not being the primary mechanism of action. Analogues
      joined by an (CH(2))(2)NR(CH(2))(2)NR(CH(2))(2) linker were extremely potent
      cytotoxins, with selectivity toward the human cell lines, but absolute potencies
      declined sharply from R = H through R = Me to R = Pr and Bu. In contrast,
      (CH(2))(2)NR(CH(2))(3)NR(CH(2))(2) compounds showed reverse effects, with the R =
      Me analogue being more potent than the R = H one as well as being the most potent
      in the series [IC(50) in JL(C) cells 0.08 nM; superior to that for the clinical
      bis(naphthalimide) LU 79553]. Overall, the IC(50)s of analogues with linker
      chains (CH(2))(n)NH(CH(2))(m)NH(CH(2))(n) were inversely proportional to linker
      length. Constraining the rigidity of the linker chain by incorporating a
      piperazine ring did not decrease potency significantly. A representative compound
      bound tightly to DNA with high selectivity for GC sites, compatible with recent
      work suggesting that compounds of this type place their side chains in the major
      groove, making specific contacts with guanine bases. Representative compounds
      were susceptible to transport mediated resistance, being much less effective in
      cells that overexpressed P-glycoprotein. Overall the results suggest these
      compounds have a similar mode of action, mediated primarily by poisoning of topo
      I (possibly with some involvement of topo II). The bis(9-methylphenazine-1
      carboxamides) show very high in vitro growth inhibitory potencies compared to
      their monomeric analogues. Two compounds showed in vivo activity in murine colon
      38 syngeneic and HT29 human colon tumor xenograft models using intraperitoneal
      dosing.

PMID- 11311064
TI  - N-Methyl scan of somatostatin octapeptide agonists produces interesting effects
      on receptor subtype specificity.
AB  - The search for synthetic analogues of somatostatin which exhibit selective
      affinities for the five receptor subtypes is of considerable basic and
      therapeutic interest and has generated a large number of potent agonist analogues
      with a wide spectrum of binding profiles. In the past, conformational restriction
      of side chain groups and the peptide backbone has yielded the most interesting
      results. Under the latter category and as part of the present study, we were
      interested in the potential effects of N-methylation of peptide bond NH groups on
      binding affinity since this approach had not been systematically examined with
      these peptides. This was aided by new chemistries for introducing an N-Me group
      during regular solid-phase peptide synthesis using Boc protection. A number of
      interesting effects were noted on relative binding affinities of the two series
      of agonist sequences chosen, DPhe(5)(or Tyr(5))-c[Cys(6)-Phe(7)-DTrp(8)-Lys(9)
      Thr(10)-Cys(11)]Thr(12)-NH(2) (SRIF numbering), at the five known human
      somatostatin receptors transfected into and stably expressed by CHO cells. N
      Methylation of residues 7 (Phe), 10 (Thr), 11 (Cys), and 12 (Thr) largely
      destroyed affinities for all five receptors. N-Methylation of DTrp in the DPhe
      series gave an analogue with extraordinarily high affinity for the type 5
      receptor for which it was also quite selective. N-Methylation of Lys in both
      series resulted in retention of type 2 affinity despite this residue constituting
      the "active center" of somatostatin peptides. N-Methylation of either the N
      terminal Tyr residue or of Cys(6) in the Tyr series resulted in analogues with
      extraordinarily high affinity for the type 3 receptor, also with a degree of
      specificity. N-Methylation of the peptide bond constrains the conformational
      space of the amino acid and eliminates the possibility of donor hydrogen bond
      formation from the amide linkage. The beta-bend conformation of the agonists
      around DTrp-Lys is stabilized by a transannular intramolecular hydrogen bond(s)
      between Phe(7) and Thr(10) so methylation of these residues eliminates this
      source of stabilization. It is expected that several of these analogues will
      provide additional tools for determining some of the physiological roles played
      by type 3 and 5 somatostatin receptors which are still far from being fully
      elucidated.

PMID- 11311065
TI  - Antitumor agents. 207. Design, synthesis, and biological testing of 4beta-anilino
      2-fluoro-4'-demethylpodophyllotoxin analogues as cytotoxic and antiviral agents.
AB  - 2-Fluoropodophyllotoxin (11) and several 4beta-anilino-2-fluoro-4'-O-demethyl
      analogues were synthesized and evaluated in both antineoplastic and antiviral
      assays. These compounds were moderately active against some cancer cell lines,
      but they were less active than the corresponding nonfluorinated analogues.
      Compound 11 exhibited the best activity against KB carcinoma with a GI(50) of
      approximately 30 nM. Most compounds exhibited moderate activity against HCMV with
      ID(50) and ID(90) values in the range of 1 microM and 4 microM, respectively.
      Both 9 and 11 showed an unusual 10-fold selectivity for HSV-2 compared to HSV-1.

PMID- 11311066
TI  - Design, synthesis, and discovery of a novel CCR1 antagonist.
AB  - The CC chemokines may play an important role in the pathogenesis of chronic
      inflammatory diseases including rheumatoid arthritis, and their effects are
      thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor
      antagonists that showed high affinity for human CCR1 receptors have been
      identified; however, their effectiveness in animal models of inflammatory
      diseases has been scarcely demonstrated, probably due to species selectivity of
      the antagonists. To elucidate the pathophysiological role of CCR1 receptors in
      murine models of disease, we looked for a potent antagonist for both murine and
      human CCR1 receptors. Screening of our chemical collection for inhibition of
      (125)I-MIP-1alpha binding to human CCR1 receptors transfected in CHO cells led to
      the identification of xanthene-9-carboxamide 1a as the lead compound.
      Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl
      groups and by installing substituents into the xanthene moiety dramatically
      improved the inhibitory activity against both human and murine CCR1 receptors. As
      a result, 2q-1 showing IC(50) values of 0.9 and 5.8 nM for human and murine CCR1
      receptors, respectively, was discovered. This compound is the first murine CCR1
      receptor antagonist and may be a useful tool for clarifying the role of CCR1
      receptors in murine models of disease.

PMID- 11311067
TI  - Discovery of novel N-phenylglycine derivatives as potent and selective beta(3)
      adrenoceptor agonists for the treatment of frequent urination and urinary
      incontinence.
AB  - With a novel assay using isolated ferret detrusor to estimate beta(3)
      adrenoceptor agonistic activity, we found that a series of glycine derivatives of
      ritodrine, a beta(2)-adrenoceptor agonist, are potent beta(3)-adrenoceptor
      agonists, with excellent selectivity versus beta(1) and beta(2) subtypes.
      Substitution of halogens in the phenyl ring increased potency and selectivity for
      the beta(3)-adrenoceptor, and this was dependent upon the position of the
      halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta(3)
      adrenoceptor-mediated relaxation of ferret detrusor (EC(50) = 0.93, 11, 14, and
      160 nM) and higher potency at beta(3)-adrenoceptors than at beta(1) or beta(2).
      The intravenous administration of 3h significantly reduced the urinary bladder
      pressure in anesthetized male rats (ED(50) = 48 microg/kg) without cardiovascular
      side effects. This article is the first report of structure-activity
      relationships (SAR) concerning beta(3)-adrenoceptor agonists as agents for the
      treatment of urinary frequency and incontinence.

PMID- 11311068
TI  - Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of
      fluorinated 2-(4-aminophenyl)benzothiazoles.
AB  - Synthetic routes to a series of mono- and difluorinated 2-(4-amino-3-substituted
      phenyl)benzothiazoles have been devised. Whereas mixtures of regioisomeric 5- and
      7-fluoro-benzothiazoles were formed from the established Jacobsen cyclization of
      precursor 3-fluoro-thiobenzanilides, two modifications to this general process
      have allowed the synthesis of pure samples of these target compounds. Fluorinated
      2-(4-aminophenyl)benzothiazoles were potently cytotoxic (GI(50) < 1 nM) in vitro
      in sensitive human breast MCF-7 (ER+) and MDA 468 (ER-) cell lines but inactive
      (GI(50) > 10 microM) against PC 3 prostate, nonmalignant HBL 100 breast, and HCT
      116 colon cells. The biphasic dose-response relationship characteristically shown
      by the benzothiazole series against sensitive cell lines was exhibited by the 4-
      and 6-fluoro-benzothiazoles (10b,d) but not by the 5- and 7-fluoro-benzothiazoles
      (10h,i). The most potent broad spectrum agent in the NCI cell panel was 2-(4
      amino-3-methylphenyl)-5-fluorobenzothiazole (10h) which, unlike the 6-fluoro
      isomer (10d), produces no exportable metabolites in the presence of sensitive MCF
      7 cells. Induction of cytochrome P450 CYP1A1, a crucial event in determining the
      antitumor specificity of this series of benzothiazoles, was not compromised. 10h
      is currently the focus of pharmaceutical and preclinical development.

PMID- 11311069
TI  - (4-Piperidin-1-yl)phenyl amides: potent and selective human beta(3) agonists.
AB  - In search of potent and selective human beta(3) agonists as potential drugs for
      the treatment of human obesity and type II diabetes, a series of (4-piperidin-1
      yl)phenyl amides was prepared and evaluated for their biological activity on the
      human beta(3)-adrenergic receptor. The leucine derivative 26e and the reverse
      amide 33b were found to be the two most potent and selective compounds in this
      study. With EC(50) values of 0.008 and 0.009 microM, respectively, at the beta(3)
      receptor, nearly completely abolished intrinsic activity at either the beta(1) or
      beta(2) receptor, and significant thermogenesis effects on human beta(3)
      adrenergic receptor transgenic mice, 26e and33b are among the most potent and
      selective human beta(3) agonists known to date.

PMID- 11311070
TI  - Efficient preparations of the beta-glucuronides of dihydroartemisinin and
      structural confirmation of the human glucuronide metabolite.
AB  - New and greatly improved preparations of the 12alpha,1'beta- (5) and
      12beta,1'beta- (6) glucuronides of dihydroartemisinin (DHA, 2) are reported using
      anomeric hydroxy and imidate glucuronate intermediates. Comparison of the
      synthetic and natural materials shows that the human metabolite of DHA is the
      12alpha-epimer 5.

PMID- 11311071
TI  - Effect of N-alkyl and N-alkenyl substituents in noroxymorphindole, 17-substituted
      6,7-dehydro-4,5alpha-epoxy-3,14-dihydroxy-6,7:2',3'-indolomorphinans, on opioid
      receptor affinity, selectivity, and efficacy.
AB  - The N-alkyl analogues (N-ethyl through N-heptyl), branched N-alkyl chain
      analogues (N-isopropyl, N-2-methylpropyl, and N-3-methylbutyl), and N-alkenyl
      analogues ((E)-N-3-methylallyl (crotyl), N-2-methylallyl, and N-3,3
      dimethylallyl) were prepared in the noroxymorphindole series (17-substituted-6,7
      dehydro-4,5alpha-epoxy-3,14-dihydroxy-6,7:2',3'-indolomorphinans), and the effect
      of the N-substituent on opioid receptor affinity, selectivity, and efficacy was
      examined using receptor binding assays, [(35)S]GTPgammaS efficacy determinations,
      and smooth muscle functional assays (electrically stimulated mouse vas deferens
      and guinea pig ileum). All of the compounds acted as opioid antagonists,
      including those with N-substituents which usually confer either weak agonist
      antagonist behavior (N-ethyl) or potent opioid agonist activity (N-pentyl) in
      morphinan-like ligands which interact with the mu-receptor. Several N-substituted
      noroxymorphindoles were found to be more mu/delta-selective than naltrindole
      (NTI). The N-2-methylallylnoroxymorphindole, in particular, was found to be more
      selective than NTI in receptor binding assays (mu/delta = 1700 vs 120;
      kappa/delta = 810 vs 140), as an antagonist in the GTPgammaS assay (mu/delta =
      170 vs 140; kappa/delta = 620 vs 160), and considerably more selective than NTI
      in the functional assays (mu/delta > 2200 vs 90). It also had high affinity for
      the delta-opioid receptor (K(i) = 4.7 nM in the binding assay) and high
      antagonist potency (1.2 nM in the GTPgammaS assay; 8.9 nM in the MVD assay).

PMID- 11311072
TI  - Synthesis and structural studies of aza analogues of functionalized amino acids:
      new anticonvulsant agents.
AB  - We have reported that functionalized amino acids 1 display potent anticonvulsant
      activities in mice and rats, and that the activity resides primarily in the D
      isomer. In this study we investigated whether selectively replacing the C(2)
      tetrahedral atom with a trivalent nitrogen provides compounds with comparable
      activity. Six functionalized N(2)-substituted semicarbazides (3) were prepared. X
      ray crystallographic analysis of 1-acetyl-4-benzyl-2-(thiazol-2-yl)semicarbazide
      (13) showed that it lost asymmetry and adopted a configuration midway between the
      corresponding D- and L-amino acid derivatives. Evaluation of 3 in both mice (ip)
      and rats (po) showed that the compounds exhibited significant anticonvulsant
      activities but in most cases at levels lower than their amino acid counterparts.
      One of the semicarbazides, 13, displayed excellent activity in mice and rats that
      compared favorably to that of phenytoin.

PMID- 11311074
TI  - Nitric oxide deficiency as a cause of clinical hypertension: promising new drug
      targets for refractory hypertension.

PMID- 11311075
TI  - Advances in pediatric dermatology: specialist training to Internet atlas.

PMID- 11311076
TI  - Antibiotics show promise as therapy for genetic disorders.

PMID- 11311077
TI  - Medical societies unite against firearm injuries.

PMID- 11311078
TI  - Stent + radiation no sure cure for stenosis.

PMID- 11311083
TI  - Safety of bolus vs infusion thrombolytic therapy.

PMID- 11311085
TI  - Safety reporting in clinical trials.

PMID- 11311086
TI  - Safety reporting in clinical trials.

PMID- 11311087
TI  - Safety reporting in clinical trials.

PMID- 11311088
TI  - Safety reporting in clinical trials.

PMID- 11311090
TI  - Bedside rationing of health care.

PMID- 11311092
TI  - Raloxifene for breast cancer prevention.

PMID- 11311094
TI  - Isotretinoin and pregnancy.

PMID- 11311096
TI  - Persistent pain in nursing home residents.

PMID- 11311097
TI  - Lamivudine-zidovudine combination for prevention of maternal-infant transmission
      of HIV-1.
AB  - CONTEXT: Zidovudine reduces maternal-infant transmission of human
      immunodeficiency virus 1 (HIV-1) infection by two thirds. Combination
      antiretroviral therapies are potentially more effective prevention. OBJECTIVES:
      To assess the safety of perinatal lamivudine-zidovudine therapy, especially in
      children, and its effects on viral load, acquisition of drug resistance, and
      maternal-infant transmission of HIV-1 in a nonbreastfeeding population. DESIGN
      AND SETTING: The Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study, an
      open-label, nonrandomized intervention trial conducted in the context of an
      ongoing observational cohort study in 48 sites in France. PATIENTS: A total of
      445 HIV-1-infected pregnant women were enrolled as the study cohort from February
      1997 to September 1998; controls consisted of 899 pregnant women who had received
      zidovudine monotherapy in May 1994 to February 1997 as standard care.
      INTERVENTION: The study cohort received lamivudine in addition to the standard
      Pediatric AIDS Clinical Trial Group 076 Study zidovudine prophylaxis regimen.
      Lamivudine was initiated in women at 32 weeks' gestation through delivery at 150
      mg twice per day orally; children received lamivudine, 2 mg/kg twice per day for
      6 weeks. MAIN OUTCOME MEASURES: HIV-1 infection status and tolerance of therapy
      in children through age 18 months; maternal plasma HIV-1 RNA levels through 6
      weeks after delivery. RESULTS: The transmission rate in the study group was 1.6%
      (7/437; 95% confidence interval [CI], 0.7%-3.3%). In a multivariable analysis,
      transmission in the study group was 5-fold lower than in controls. In the study
      group, maternal plasma HIV-1 RNA level was less than 500 copies/mL at delivery in
      74%; the median decrease was 1.24 (range, -1.63 to 3.40) log(10) copies/mL. The
      M184V lamivudine resistance mutation was detected at 6 weeks after delivery in
      specimens from 52 of 132 women. The most frequent serious adverse events in
      children were neutropenia and anemia, requiring blood transfusion in 9 children
      and premature treatment discontinuation in 19. Two uninfected children died at
      age 1 year from neurologic complications related to mitochondrial dysfunction.
      CONCLUSIONS: Lamivudine-zidovudine may be effective in preventing maternal-infant
      HIV transmission. However, severe adverse effects and emergence of resistance to
      lamivudine occurred. Thus, the role of this combination therapy in this setting
      is as yet unclear, and further research involving a variety of strategies is
      needed to definitively ascertain its utility for preventing maternal-infant HIV
      transmission.

PMID- 11311098
TI  - Bullying behaviors among US youth: prevalence and association with psychosocial
      adjustment.
AB  - CONTEXT: Although violence among US youth is a current major concern, bullying is
      infrequently addressed and no national data on the prevalence of bullying are
      available. OBJECTIVES: To measure the prevalence of bullying behaviors among US
      youth and to determine the association of bullying and being bullied with
      indicators of psychosocial adjustment, including problem behavior, school
      adjustment, social/emotional adjustment, and parenting. DESIGN, SETTING, AND
      PARTICIPANTS: Analysis of data from a representative sample of 15 686 students in
      grades 6 through 10 in public and private schools throughout the United States
      who completed the World Health Organization's Health Behaviour in School-aged
      Children survey during the spring of 1998. MAIN OUTCOME MEASURE: Self-report of
      involvement in bullying and being bullied by others. RESULTS: A total of 29.9% of
      the sample reported moderate or frequent involvement in bullying, as a bully
      (13.0%), one who was bullied (10.6%), or both (6.3%). Males were more likely than
      females to be both perpetrators and targets of bullying. The frequency of
      bullying was higher among 6th- through 8th-grade students than among 9th- and
      10th-grade students. Perpetrating and experiencing bullying were associated with
      poorer psychosocial adjustment (P<.001); however, different patterns of
      association occurred among bullies, those bullied, and those who both bullied
      others and were bullied themselves. CONCLUSIONS: The prevalence of bullying among
      US youth is substantial. Given the concurrent behavioral and emotional
      difficulties associated with bullying, as well as the potential long-term
      negative outcomes for these youth, the issue of bullying merits serious
      attention, both for future research and preventive intervention.

PMID- 11311099
TI  - Long-term MI outcomes at hospitals with or without on-site revascularization.
AB  - CONTEXT: Many studies have found that patients with acute myocardial infarction
      (AMI) who are admitted to hospitals with on-site revascularization facilities
      have higher rates of invasive cardiac procedures and better outcomes than
      patients in hospitals without such facilities. Whether such differences are due
      to invasive procedure rates alone or to other patient, physician, and hospital
      characteristics is unknown. OBJECTIVE: To determine whether invasive procedural
      rate variations alone account for outcome differences in patients with AMI
      admitted to hospitals with or without on-site revascularization facilities.
      DESIGN: Retrospective, observational cohort study using linked population-based
      administrative data from a universal health insurance system. SETTING: One
      hundred ninety acute care hospitals in Ontario, 9 of which offered invasive
      procedures. PATIENTS: A total of 25 697 patients hospitalized with AMI between
      April 1, 1992, and December 31, 1993, of whom 2832 (11%) were in invasive
      hospitals. MAIN OUTCOME MEASURES: Mortality, recurrent cardiac hospitalizations,
      and emergency department visits in the 5 years following the index admission,
      adjusted for patient age, sex, socioeconomic status, illness severity, and index
      revascularization procedures; attending physician specialty; and hospital volume,
      teaching status, and geographical proximity to invasive-procedure centers and
      compared by hospital type. RESULTS: Patients admitted to invasive-procedure
      hospitals were much more likely to undergo revascularization (11.4% vs 3.2% at
      other hospitals; P<.001). However, many other clinical and process-related
      factors differed between the 2 groups. Although mortality rates were similar
      between the 2 institution types, the nonfatal composite 5-year event rate (ie,
      recurrent cardiac hospitalization and emergency department visits) was lower for
      patients initially admitted to invasive-procedure hospitals (71.3% vs 80.4%;
      unadjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.52-0.82;
      P<.001). This advantage persisted after adjustment for sociodemographic and
      clinical factors and procedure utilization (adjusted OR, 0.68; 95% CI, 0.53-0.89;
      P<.001). However, the nonfatal outcome advantages of invasive-procedure hospitals
      were explained by their teaching status (adjusted OR, 0.98; 95% CI, 0.73-1.30; P
      =.87). CONCLUSIONS: In this sample of patients admitted with AMI, the differing
      outcomes of apparently similar patients treated in 2 different practice settings
      were explained by multiple competing factors. Researchers conducting
      observational studies should be cautious about attributing patient outcome
      differences to any single factor.

PMID- 11311100
TI  - Relation of impaired fasting and postload glucose with incident type 2 diabetes
      in a Dutch population: The Hoorn Study.
AB  - CONTEXT: Persons with impaired glucose tolerance (IGT) are known to have an
      elevated risk of developing diabetes mellitus. Less is known about diabetes risk
      among persons with impaired fasting glucose (IFG) or with normal glucose levels.
      OBJECTIVE: To determine the incidence of diabetes in relation to baseline fasting
      and postload glucose levels and other risk factors. DESIGN, SETTING, AND
      PARTICIPANTS: Population-based cohort study conducted from October 1989 to
      February 1992 among 1342 nondiabetic white residents of Hoorn, the Netherlands,
      aged 50 to 75 years at baseline, in whom fasting plasma glucose (FPG) levels and
      glucose levels 2 hours after a 75-g oral glucose tolerance test were measured at
      baseline and at follow-up in 1996-1998. MAIN OUTCOME MEASURES: Cumulative
      incidence of diabetes, defined according to the diagnostic criteria of the World
      Health Organization (WHO-1985 and WHO-1999) and the American Diabetes Association
      (ADA-1997), during a mean follow-up of 6.4 years, compared among participants
      with IFG, IGT, and normal glucose levels at baseline. RESULTS: The cumulative
      incidence of diabetes was 6.1%, 8.3%, and 9.9% according to the WHO-1985, ADA,
      and WHO-1999 criteria, respectively. The cumulative incidence of diabetes (WHO
      1999 criteria) for participants with both IFG and IGT was 64.5% compared with
      4.5% for those with normal glucose levels at baseline. The odds ratios for
      diabetes (WHO-1999 criteria), adjusted for age, sex, and follow-up duration, were
      10.0 (95% confidence interval [CI], 6.1-16.5), 10.9 (95% CI, 6.0-19.9), and 39.5
      (95% CI, 17.0-92.1), respectively, for those having isolated IFG, isolated IGT,
      and both IFG and IGT. In addition to FPG and 2-hour postload glucose levels
      (P<.001 for both), the waist-hip ratio also was an important risk factor for
      developing diabetes (P =.002). CONCLUSION: In this study, the cumulative
      incidence of diabetes was strongly related to both IFG and IGT at baseline and,
      in particular, to the combined presence of IFG and IGT.

PMID- 11311101
TI  - Medication errors and adverse drug events in pediatric inpatients.
AB  - CONTEXT: Iatrogenic injuries, including medication errors, are an important
      problem in all hospitalized populations. However, few epidemiological data are
      available regarding medication errors in the pediatric inpatient setting.
      OBJECTIVES: To assess the rates of medication errors, adverse drug events (ADEs),
      and potential ADEs; to compare pediatric rates with previously reported adult
      rates; to analyze the major types of errors; and to evaluate the potential impact
      of prevention strategies. DESIGN, SETTING, AND PATIENTS: Prospective cohort study
      of 1120 patients admitted to 2 academic institutions during 6 weeks in April and
      May of 1999. MAIN OUTCOME MEASURES: Medication errors, potential ADEs, and ADEs
      were identified by clinical staff reports and review of medication order sheets,
      medication administration records, and patient charts. RESULTS: We reviewed 10
      778 medication orders and found 616 medication errors (5.7%), 115 potential ADEs
      (1.1%), and 26 ADEs (0.24%). Of the 26 ADEs, 5 (19%) were preventable. While the
      preventable ADE rate was similar to that of a previous adult hospital study, the
      potential ADE rate was 3 times higher. The rate of potential ADEs was
      significantly higher in neonates in the neonatal intensive care unit. Most
      potential ADEs occurred at the stage of drug ordering (79%) and involved
      incorrect dosing (34%), anti-infective drugs (28%), and intravenous medications
      (54%). Physician reviewers judged that computerized physician order entry could
      potentially have prevented 93% and ward-based clinical pharmacists 94% of
      potential ADEs. CONCLUSIONS: Medication errors are common in pediatric inpatient
      settings, and further efforts are needed to reduce them.

PMID- 11311102
TI  - A 45-year-old woman with obsessive-compulsive disorder.

PMID- 11311103
TI  - A 33-year-old woman with morbid obesity, 1 year later.

PMID- 11311104
TI  - Combination prophylaxis for prevention of maternal-infant HIV transmission:
      beyond 076.

PMID- 11311105
TI  - The need to address bullying-an important component of violence prevention.

PMID- 11311111
TI  - Inhibitors of leukotriene A4 (LTA4) hydrolase as potential anti-inflammatory
      agents.
AB  - Leukotriene A4 (LTA4) hydrolase is a zinc-containing enzyme which
      stereospecifically catalyzes the hydrolysis of the epoxide LTA4 to the diol
      leukotriene B4 (LTB4). There is substantial evidence that LTB4 plays a
      significant role in the amplification of many inflammatory disease states.
      Therapeutic agents which selectively inhibit LTA4 hydrolase would block the
      formation of LTB4 and thus be potentially useful for the treatment of
      inflammation. Numerous inhibitors of LTA4 hydrolase have been reported over the
      past 15-20 years. Several early inhibitors were based on the structure of the
      natural substrate, LTA4. Later approaches utilized known inhibitors of related
      zinc-containing metalloproteinases and led to the identification of captopril,
      bestatin and kelatorphan as potent inhibitors of LTA4 hydrolase. This led to the
      design of a number of peptide and non-peptide analogs which contained potential
      zinc-chelating moieties, including thiols, hydroxamates and norstatines. A more
      recent series of non-peptidic, non-zinc chelating inhibitors of LTA4 hydrolase
      has been reported. This work led to the identification of several novel classes
      of analogs, including imidazopyridines, amidines and cyclic and acyclic amino
      acid derivatives, ultimately resulting in the identification of two potential
      clinical candidates SC-56938 and SC-57461A.

PMID- 11311112
TI  - An update on inhibitors of human 14 kDa Type II s-PLA2 in development.
AB  - Recent progress in the development of inhibitors of human Type II s-PLA2 as
      potential anti-inflammatory agents is presented. While many companies have
      curtailed their efforts in the PLA2 area, Eli Lilly and Shionogi are continuing
      to advance LY-315920 (S-5920) as a potential treatment for sepsis and other
      diseases that have an inflammatory component. The Lilly developmental effort
      leading to LY-315920 is extensively reviewed, as well as the current status of
      other small molecular weight inhibitors of Type II s-PLA2 that have been reported
      to be in late-stage development

PMID- 11311113
TI  - Novel mechanistic targets for the treatment of sub-acute and chronic bronchitis.
AB  - Sub-acute and chronic bronchitis (SACB) are among the least well studied major
      medical problems that exist today. While much research and novel drug discovery
      have focused on asthma, comparatively little has been performed on chronic
      bronchitis, the fourth or fifth most frequent disease (4 to 6% of the population
      over 45 years of age), or on sub-acute bronchitis, the persistent symptoms of a
      respiratory infection which is the major reason Americans visit a physician
      (20%). This lack of attention is largely due to difficulties associated with
      modeling the pathophysiology of SACB in vitro, in situ, in organs or in animals
      as well as the presumption that drugs developed for asthma would also be
      effective in SACB. Data with bronchodilators (anti-cholinergics versus beta2
      adrenergic agonist) and corticosteroids have strongly dismissed that premise. In
      this review of potential novel mechanistic targets directed specifically at SACB,
      an emphasis is given to recent data, gathered most convincingly from tissues and
      patients with cystic fibrosis, that have led to an appreciation of the critical
      role respiratory epithelial dysfunction plays in the pathophysiology and symptoms
      of these diseases. Mechanistic targets that restore (normalize or accelerate)
      airway 'cleansing' (enhance host defense) by accelerating mucociliary clearance
      are described and given preference over anti-inflammatory mechanisms that could
      further impair host defense.

PMID- 11311114
TI  - Current and potential agents for the treatment of alopecia areata.
AB  - Alopecia areata is considered to be a T-cell mediated autoimmune disease of the
      hair follicle. Current immunosuppressive approaches and immunomodulatory
      treatment with contact sensitizers such as diphenylcyclopropenone and squaric
      acid dibutylester are dealt with in this review article. The efficacy of the
      various modes of treatment is evaluated by a review of literature and their mode
      of action is discussed. In accordance with the mechanism of autoimmune
      pathogenesis of AA, improved future treatments may be immunosuppressive or
      immunomodulatory, or they should otherwise protect the hair follicle from the
      injurious effects of the inflammation. Such possible future therapeutic
      approaches include the use of liposomes as an improved vehicle, application of
      immunosuppressive cytokines like TGF-beta and IL-10, inhibition of apoptosis
      mediated by the Fas-FasL system, inhibition of the lymphocyte homing receptor
      CD44v10, induction of tolerance as well as principles of gene therapy.

PMID- 11311116
TI  - Subcellular localization and adaptive up-regulation of the System A (SAT2) amino
      acid transporter in skeletal-muscle cells and adipocytes.
AB  - The recently cloned amino acid transporter SAT2 is ubiquitously expressed and
      confers Na(+)-dependent transport of short-chain neutral amino acids,
      characteristics of the functionally defined System A transporter. Here we report
      the presence of SAT2 mRNA and protein in both skeletal muscle and adipocytes, and
      the characterization of polyclonal antibodies directed against this transporter.
      SAT2 protein was present in both plasma-membrane and internal-membrane fractions
      derived from rat skeletal muscle and adipose tissue, L6 myotubes and 3T3-L1
      adipocytes, having a localization similar to that of the glucose transporter
      GLUT4. Moreover, consistent with the adaptive up-regulation of System A activity
      following chronic amino acid deprivation, a time-dependent increase in SAT2
      protein abundance was observed in amino-acid-deprived L6 myotubes and 3T3-L1
      adipocytes. These studies provide the first evidence regarding the subcellular
      distribution and adaptive up-regulation of SAT2 protein and the characterization
      of molecular probes for this physiologically important transporter, the function
      of which is altered in several disease states.

PMID- 11311115
TI  - Electrospray and tandem mass spectrometry in biochemistry.
AB  - Over the last 20 years, biological MS has changed out of all recognition. This is
      primarily due to the development in the 1980s of 'soft ionization' methods that
      permit the ionization and vaporization of large, polar, and thermally labile
      biomolecules. These developments in ionization mode have driven the design and
      manufacture of smaller and cheaper mass analysers, making the mass spectrometer a
      routine instrument in the biochemistry laboratory today. In the present review
      the revolutionary 'soft ionization' methods will be discussed with particular
      reference to electrospray. The mass analysis of ions will be described, and the
      concept of tandem MS introduced. Where appropriate, examples of the application
      of MS in biochemistry will be provided. Although the present review will
      concentrate on the MS of peptides/proteins and lipids, all classes of
      biomolecules can be analysed, and much excellent work has been done in the fields
      of carbohydrate and nucleic acid biochemistry.

PMID- 11311117
TI  - Controlled protonation of iron-molybdenum cofactor by nitrogenase: a structural
      and theoretical analysis.
AB  - Qualitative molecular modelling has been used to identify possible routes for
      transfer of protons from the surface of the nitrogenase protein to the iron
      molybdenum cofactor (FeMoco) and to substrates during catalysis. Three proton
      transfer routes have been identified; a water-filled channel running from the
      protein exterior to the homocitrate ligand of FeMoco, and two hydrogen-bonded
      chains to specific FeMoco sulphur atoms. It is suggested that the water channel
      is used for multiple proton deliveries to the substrate, as well as in diffusion
      of products and substrates between FeMoco and the bulk solvent, whereas the two
      hydrogen-bonded chains each allow a single proton to be added to, and
      subsequently depart from, FeMoco during the catalytic cycle. Possible functional
      differences in the proton-transfer channels are discussed in terms of assessment
      of the protein environment and specific hydrogen-bonding effects. The
      implications of these observations are discussed in terms of the suppression of
      wasteful production of dihydrogen by nitrogenase and the Lowe-Thorneley scheme
      for dinitrogen reduction.

PMID- 11311118
TI  - Murine fibromodulin: cDNA and genomic structure, and age-related expression and
      distribution in the knee joint.
AB  - The genomic structure of murine fibromodulin was determined, and its age-related
      expression and distribution were characterized in knee epiphyses, with decorin
      studied for reference. Fibromodulin, as well as decorin, have roles in collagen
      fibrillogenesis both in vitro and in vivo. The murine fibromodulin gene, Fmod,
      was similar with that in other species, with three exons and 86% of the
      translated sequence in exon 2. The 2.7 kb long cDNA contains an open reading
      frame of 1131 nt. Fibromodulin mRNA levels were highest in tissues rich in
      fibrillar collagens type I or type II. During growth, the distribution of
      fibromodulin mRNA was similar with that of type II collagen, with the highest
      levels between 5 days and 1 month of age. Thereafter, the expression of type II
      collagen declined to a level near the detection limit, whereas the fibromodulin
      expression decreased less markedly to a level of approx. 35% of maximum, and
      remained constant throughout the rest of the observation period. In contrast,
      decorin mRNA levels were the highest in old animals. Pericellular deposition of
      fibromodulin was strong around the late-hypertrophic chondrocytes of the
      secondary ossification centre and in the growth plate. In young epiphyses, both
      fibromodulin and decorin were found interterritorially, mainly in the uncalcified
      and deep-calcified cartilage. In the old mice, calcified cartilage became
      enriched with regard to fibromodulin, while, in contrast, decorin deposition
      diminished, particularly near the tidemark. In the subchondral bone trabeculae,
      decorin was found in the endosteum of growing, but not in the mature, epiphyses.
      Differences in the expression and distribution profiles suggest different roles
      for fibromodulin and decorin in the regulation of collagen fibrillogenesis,
      maintenance of the fibril organization and matrix mineralization. As fibromodulin
      is deposited closer to cells than decorin, it may have a primary role in collagen
      fibrillogenesis, whereas decorin might be involved in the maintenance of fibril
      structures in the interterritorial matrix.

PMID- 11311119
TI  - Expression of P-170 glycoprotein sensitizes lymphoblastoid CEM cells to
      mitochondria-mediated apoptosis.
AB  - Multidrug resistance caused by P-glycoprotein (P-170) is a phenomenon by which
      cells exposed to a single drug acquire resistance to other structurally and
      functionally unrelated drugs. This is a widespread phenomenon described in vivo
      in the management of infectious as well as non-infectious diseases. Several in
      vitro models have been developed in order to evaluate physiopathological
      properties of P-170. Among these are P-170-expressing variants of the human T
      lymphoblastoid CEM cell line called VBL100. As a general rule, drug resistance
      normally results in resistance to apoptosis induction. By contrast, a paradoxical
      activity is exerted in this cell model by the cytokine tumour necrosis factor
      alpha (TNF-alpha), which is capable of inducing apoptosis in P-170-expressing
      variants better than in wild-type (wt) cells. In the present study we partially
      address the mechanisms underlying this activity. In fact, the susceptibility of
      VBL100 cells to TNF-alpha appears to be specifically due to the depolarization of
      their mitochondrial membrane, a key factor for apoptotic induction. The same was
      observed with staurosporine, a specific mitochondrion-mediated proapoptotic
      chemical probe. Conversely, other proapoptotic stimuli, such as Fas/CD95 or the
      anti-cancer drug etoposide, did induce significant cell death in wild type cells
      only. Thus, schematically, mitochondrially dependent stimuli appeared to be more
      effective in VBL100-cell killing, while 'physiological' stimuli showed the
      opposite behaviour. Importantly, under steady-state conditions, VBL100 cells
      displayed per se a mitochondrial membrane hyperpolarization that appeared
      strictly related to their high susceptibility to specific apoptotic stimuli. In
      conclusion, the study of a well-established cell model such as that represented
      by the wt/VBL CEM lymphoid cell line seems to suggest that the multidrug
      resistance phenotype can specifically sensitize cells towards 'unphysiological',
      mitochondria-associated cell death cascade or, in the same fashion, it could
      shift cells from type I (mainly plasma membrane-associated) towards type II
      (mainly mitochondrial membrane-associated) phenotype.

PMID- 11311120
TI  - The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in
      vitro, a novel in vivo phosphorylation site.
AB  - Forkhead in rhabdomyosarcoma (FKHR) is a transcription factor that has been
      implicated in the control of gene expression by insulin, as well as the
      regulation of apoptosis by survival factors. These signals trigger the protein
      kinase B (PKB)-catalysed phosphorylation of FKHR at three residues (Thr(24),
      Ser(256) and Ser(319)) by a phosphoinositide 3-kinase-dependent pathway that
      results in the nuclear exit and inactivation of this transcription factor. Here,
      we have identified a conserved residue (Ser(329)) as a novel in vivo
      phosphorylation site on FKHR. Ser(329) phosphorylation also decreases the ability
      of FKHR to stimulate gene transactivation and reduces the proportion of FKHR
      present in the nucleus. However, unlike the residues targetted by PKB, Ser(329)
      is phosphorylated in unstimulated HEK-293 cells, and phosphorylation is not
      increased by stimulation with insulin-like growth factor-1 or by transfection
      with 3-phosphoinositide-dependent protein kinase-1. We have also purified a
      protein kinase to near homogeneity from rabbit skeletal muscle that
      phosphorylates FKHR at Ser(329) specifically and identified it as DYRK1A (dual
      specificity tyrosine-phosphorylated and regulated kinase 1A). We find that FKHR
      and DYRK1A co-localize in discrete regions of the nucleus and can be co
      immunoprecipitated from cell extracts. These experiments suggest that DYRK1A may
      phosphorylate FKHR at Ser(329) in vivo.

PMID- 11311121
TI  - The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon
      at Ser539 and the microtubule-associated protein tau at Thr212: potential role
      for DYRK as a glycogen synthase kinase 3-priming kinase.
AB  - The substrate specificity of glycogen synthase kinase 3 (GSK3) is unusual in that
      efficient phosphorylation only occurs if another phosphoserine or
      phosphothreonine residue is already present four residues C-terminal to the site
      of GSK3 phosphorylation. One such substrate is the epsilon-subunit of rat
      eukaryotic protein-synthesis initiation factor 2B (eIF2Bepsilon), which is
      inhibited by the GSK3-catalysed phosphorylation of Ser(535). There is evidence
      that GSK3 is only able to phosphorylate eIF2Bepsilon at Ser(535) if Ser(539) is
      already phosphorylated by another protein kinase. However, no protein kinases
      capable of phosphorylating Ser(539) have so far been identified. Here we show
      that Ser(539) of eIF2Bepsilon, which is followed by proline, is phosphorylated
      specifically by two isoforms of dual-specificity tyrosine phosphorylated and
      regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other
      'proline-directed' protein kinases tested. We also establish that phosphorylation
      of Ser(539) permits GSK3 to phosphorylate Ser(535) in vitro and that eIF2Bepsilon
      is highly phosphorylated at Ser(539) in vivo. The DYRK isoforms also
      phosphorylate human microtubule-associated protein tau at Thr(212) in vitro, a
      residue that is phosphorylated in foetal tau and hyperphosphorylated in
      filamentous tau from Alzheimer's-disease brain. Phosphorylation of Thr(212)
      primes tau for phosphorylation by GSK3 at Ser(208) in vitro, suggesting a more
      general role for DYRK isoforms in priming phosphorylation of GSK3 substrates.

PMID- 11311122
TI  - Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression.
AB  - Previous studies have demonstrated that mitomycin C (MMC) and other DNA cross
      linking agents can suppress MDR1 (multidrug resistance 1) gene expression and
      subsequent functional P-glycoprotein (Pgp) expression, whereas doxorubicin and
      other anthracyclines increase MDR1 gene expression. In the present study, with
      stably transfected Madin-Darby canine kidney C7 epithelial cells expressing a
      human Pgp tagged with green fluorescent protein under the proximal human MDR1
      gene promoter, we demonstrated that MMC and doxorubicin have differential effects
      on Pgp expression and function. Doxorubicin caused a progressive increase in the
      cell-surface expression of Pgp and function. In contrast, MMC initially increased
      plasma membrane expression and function at a time when total cellular Pgp was
      constant and Pgp mRNA expression had been shown to be suppressed. This was
      followed by a rapid and sustained decrease in cell-surface expression at later
      times, presumably as a consequence of the initial decrease in mRNA expression.
      These studies imply that there are at least two independent chemosensitive steps
      that can alter Pgp biogenesis: one at the level of mRNA transcription and the
      other at the level of Pgp trafficking. Understanding the combined consequences of
      these two mechanisms might lead to novel chemotherapeutic approaches to
      overcoming drug resistance in human cancers by altering either Pgp mRNA
      expression or trafficking to the membrane.

PMID- 11311123
TI  - The hexokinase 2 protein regulates the expression of the GLK1, HXK1 and HXK2
      genes of Saccharomyces cerevisiae.
AB  - The key glycolytic HXK2 gene, coding for the enzyme hexokinase 2 (Hxk2p), is
      expressed when cells of the yeast Saccharomyces cerevisiae are grown on a
      fermentable medium using glucose, fructose or mannose as a carbon source. After
      shifting the cells to a non-fermentable carbon source, the HXK2 gene is repressed
      and the HXK1 and GLK1 genes are rapidly de-repressed, producing the enzymes
      hexokinase 1 (Hxk1p) and glucokinase (Glk1p) respectively. Because the in vivo
      functions of the Hxk1p and Glk1p enzymes have remained a mystery so far, we have
      investigated this glucose-induced regulatory process. Here we demonstrate the
      involvement of Hxk2p in the glucose-induced repression of the HXK1 and GLK1 genes
      and the glucose-induced expression of the HXK2 gene. We have also demonstrated
      the involvement of Hxk1p as a negative factor in the expression of the GLK1 and
      HXK2 genes. Further experimental evidence, using mutant cells expressing a
      truncated version of Hxk2p unable to enter the nucleus, shows that nuclear
      localization of Hxk2p is necessary for glucose-induced repression signalling of
      the HXK1 and GLK1 genes and for glucose-induced expression of the HXK2 gene. Gel
      mobility-shift analysis shows that Hxk2p-mediated regulation is exerted through
      ERA (ethanol repression autoregulation)-like regulatory sequences present in the
      HXK1 and GLK1 promoters and in two downstream repressing sequences of the HXK2
      gene. These findings reveal a novel mechanism of gene regulation whereby the
      product of a glycolytic gene, normally resident in the cytosol, interacts
      directly with nuclear proteins to regulate the transcription of the HXK1 and GLK1
      genes and to autoregulate its own transcription.

PMID- 11311124
TI  - Evaluation of the role of proline residues flanking the RGD motif of dendroaspin,
      an inhibitior of platelet aggregation and cell adhesion.
AB  - The effect of a panel of proline mutants of dendroaspin, an inhibitor of platelet
      aggregation and cell adhesion, including A(42)-dendroaspin, A(47)-dendroaspin,
      A(49)-dendroaspin, A(42,47)-dendroaspin and A(47,49)-dendroaspin, was
      investigated using platelet-aggregation and cell-adhesion assays. Here we show
      that a single alanine-for-proline substitution did not affect potency when
      measured as the ability either to inhibit platelet aggregation induced by ADP
      (IC(50) approximately 170 nM) or to block transfected A375-SM cell adhesion to
      fibrinogen in the presence of Mn(2+) as compared with wild-type dendroaspin. By
      comparison, double proline substitution with alanines significantly reduced the
      potency in both assays by approx. 5-8-fold. These observations, therefore,
      suggest that proline residues flanking the RGD motif in dendroaspin and other RGD
      containing venom proteins, e.g. disintegrins, may contribute to maintaining a
      favourable conformation for the solvent-exposed RGD site for its recognition by
      integrin receptors.

PMID- 11311125
TI  - Plasmin-dependent elimination of the growth-factor-like domain in urokinase
      causes its rapid cellular uptake and degradation.
AB  - Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in concert
      to mediate pericellular proteolysis and to stimulate intracellular signalling
      responsible for cell migration and proliferation. uPA is composed of three
      domains, a proteolytic domain (PD), a kringle domain (KD) and a growth-factor
      like domain (GFD), the last of which mediates the interaction with uPAR. We
      demonstrate that uPA, associated with the surface of U937 cells, undergoes
      plasmin-mediated cleavage of the Lys(46)-Ser(47) bond with elimination of the
      GFD. Using recombinant forms of uPA, we show that a uPA variant lacking the GFD
      (r-uPADeltaGFD) and unable to associate with uPAR is rapidly cleared from the
      cell surface. Binding and internalization of r-uPADeltaGFD are markedly decreased
      in the presence of 39 kDa receptor-associated protein (RAP), the antagonist of
      several endocytic receptors of the low-density lipoprotein receptor family,
      suggesting that this protein clearance pathway is used for r-uPADeltaGFD. In
      contrast with rapidly internalized r-uPADeltaGFD, the intact recombinant single
      chain urokinase with wild-type structure (r-uPAwt) bound to uPAR is retained on
      the cell surface. Soluble uPAR protects uPA from cleavage by plasmin that results
      in the elimination of GFD, suggesting that uPAR might protect cell-bound
      urokinase from plasmin-mediated cleavage between the GFD and KD and subsequent
      degradation.

PMID- 11311126
TI  - Tissue-specific activity of lipoprotein lipase in skeletal muscle regulates the
      expression of uncoupling protein 3 in transgenic mouse models.
AB  - Uncoupling protein (UCP)-2 and UCP-3 are two recently discovered proteins similar
      to UCP-1, which regulates thermogenesis in brown adipose tissue (BAT). Whereas
      UCP-1 expression is restricted to BAT, UCP-2 is widely expressed. UCP-3 is found
      mainly in skeletal muscle and BAT. A large body of evidence exists that the
      expression of UCP-2 and UCP-3 in skeletal muscle of mice is regulated by
      feeding/fasting, and some studies have suggested that this effect might be caused
      by the changing concentration of plasma non-esterified fatty acids (NEFAs). In an
      attempt to determine whether the increased import of triacylglycerol-derived
      NEFAs can also affect UCP expression, we determined the mRNA levels of UCP-1, UCP
      2 and UCP-3 in BAT and muscle of induced mutant mouse lines that overexpressed or
      lacked lipoprotein lipase (LPL) in these tissues. The expression levels of UCP-1
      and UCP-2 in BAT and in skeletal and cardiac muscle respectively were not
      affected by variations in tissue LPL activities. In contrast, UCP-3 mRNA levels
      were induced 3.4-fold in mice with high levels of LPL in skeletal muscle, and
      down-regulated in mice that lacked LPL in skeletal muscle. The presence or
      absence of LPL in BAT had no effect on UCP-3 expression levels. The response of
      UCP-3 mRNA expression to variations in LPL activity in skeletal muscle was
      independent of the feeding status or of plasma NEFA concentrations. These
      findings indicated that NEFAs as lipolytic products of LPL-mediated
      triacylglycerol hydrolysis markedly affect UCP-3 expression and that increased
      LPL activities occurring during fasting in skeletal muscle contribute to the
      induction of UCP-3 expression by promoting the increased uptake of NEFAs. In
      addition, our results demonstrate that UCP-2 and UCP-3 are differentially
      regulated in response to LPL-mediated NEFA uptake in skeletal muscle of mice.

PMID- 11311127
TI  - Reactive oxygen species involved in trichosanthin-induced apoptosis of human
      choriocarcinoma cells.
AB  - The type-I ribosome-inactivating protein trichosanthin (TCS) has a broad spectrum
      of biological and pharmacological activities, including abortifacient, anti
      tumour and anti-HIV activities. We have found for the first time that TCS
      stimulated the production of reactive oxygen species (ROS) in JAR cells (a human
      choriocarcinoma cell line) in a time- and concentration-dependent manner by using
      the fluorescent probe 2',7'-dichlorofluorescein diacetate with confocal laser
      scanning microscopy. ESR spectral studies and the inhibition of ROS formation by
      the superoxide radical anion (O(2)(-.)) scavenger superoxide dismutase, the
      H(2)O(2) scavenger catalase and the hydroxyl radical (OH(.)) scavenger mannitol
      suggested the involvement of O(2)(-.), H(2)O(2) and OH(.). TCS-induced ROS
      formation was shown to be dependent on the presence of both extracellular and
      intracellular Ca(2+); moreover, ROS production paralleled the intracellular
      Ca(2+) elevation induced by TCS, suggesting that ROS production might be a
      consequence of Ca(2+) signalling. TCS-induced activation of caspase-3 was
      initiated within 2 h; however, TCS-induced production of ROS was initiated within
      5 min, suggesting that the production of ROS preceded the activation of caspase
      3. Simultaneous observation of the nuclear morphological changes via two-photon
      laser scanning microscopy and ROS production via confocal laser scanning
      microscopy revealed that ROS is involved in the apoptosis of JAR cells. The
      involvement of ROS was also confirmed by the inhibition of TCS-induced cell death
      by the antioxidant Trolox and the ROS scavengers catalase and mannitol.
      Diethylenetriaminepenta-acetic acid, an inhibitor of metal-facilitated OH(.)
      formation, markedly inhibited TCS-induced cell death, suggesting that TCS induced
      OH(.) formation via the Fenton reaction. The finding that ROS is involved in the
      TCS-induced apoptosis of JAR cells might provide new insight into the anti-tumour
      and anti-HIV mechanism of TCS.

PMID- 11311128
TI  - The transient receptor potential, TRP4, cation channel is a novel member of the
      family of calmodulin binding proteins.
AB  - The mammalian gene products, transient receptor potential (trp)1 to trp7, are
      related to the Drosophila TRP and TRP-like ion channels, and are candidate
      proteins underlying agonist-activated Ca(2+)-permeable ion channels. Recently,
      the TRP4 protein has been shown to be part of native store-operated Ca(2+)
      permeable channels. These channels, most likely, are composed of other proteins
      in addition to TRP4. In the present paper we report the direct interaction of
      TRP4 and calmodulin (CaM) by: (1) retention of in vitro translated TRP4 and of
      TRP4 protein solubilized from bovine adrenal cortex by CaM-Sepharose in the
      presence of Ca(2+), and (2) TRP4-glutathione S-transferase pull-down experiments.
      Two domains of TRP4, amino acid residues 688-759 and 786-848, were identified as
      being able to interact with CaM. The binding of CaM to both domains occurred only
      in the presence of Ca(2+) concentrations above 10 microM, with half maximal
      binding occurring at 16.6 microM (domain 1) and 27.9 microM Ca(2+) (domain 2).
      Synthetic peptides, encompassing the two putative CaM binding sites within these
      domains and covering amino acid residues 694-728 and 829-853, interacted directly
      with dansyl-CaM with apparent K(d) values of 94-189 nM. These results indicate
      that TRP4/Ca(2+)-CaM are parts of a signalling complex involved in agonist
      induced Ca(2+) entry.

PMID- 11311129
TI  - Ten isoenzymes of xyloglucan endotransglycosylase from plant cell walls select
      and cleave the donor substrate stochastically.
AB  - To map the preferred cleavage sites of xyloglucan endotransglycosylases (XETs; EC
      2.4.1.207) along the donor substrate chain, we incubated the enzymes with
      tamarind (Tamarindus indica) xyloglucan (donor substrate; approximately 205 kDa;
      21 microM) plus the nonasaccharide [(3)H]XLLGol (Gal(2).Xyl(3).Glc(3).
      [(3)H]glucitol; acceptor substrate; 0.6 microM). After short incubation times, to
      minimize multiple cleavages, the size of the (3)H-labelled transglycosylation
      products (determined by gel-permeation chromatography) indicated the positions of
      the cleavage sites relative to the non-reducing terminus of the donor. There was
      very little difference between the size profiles of the products formed by any of
      ten XETs tested [one native XET purified from cauliflower (Brassica oleracea)
      florets, four native XET isoenzymes purified from etiolated mung-bean (Phaseolus
      aureus) shoots, native XETs purified from lentil (Lens culinaris) and nasturtium
      (Tropaeolum majus) seeds, and three insect-cell-produced thale-cress (Arabidopsis
      thaliana) XETs (EXGT, TCH4 and MERI-5)]. All such product profiles showed a good
      fit to a model in which the enzyme chooses its donor substrate independently of
      size and attacks it, once only, at a randomly selected cleavage site. The results
      therefore do not support the hypothesis that different XET isoenzymes are adapted
      to produce longer or shorter products such as might favour either the efficient
      integration of new xyloglucan into the cell wall or the re-structuring of old
      xyloglucan within an expanding wall.

PMID- 11311130
TI  - Phosphate-binding loop and Rab GTPase function: mutations at Ser29 and Ala30 of
      Rab5 lead to loss-of-function as well as gain-of-function phenotype.
AB  - Ras-like GTPases contain a structurally conserved GTP-binding domain. An
      important element of the GTP-binding domain is the phosphate-binding loop, which
      contains two Gly residues (Gly(12) and Gly(13)) in Ras. Because the two Gly
      residues are crucial for normal Ras function, it is intriguing that they are not
      conserved in other Ras-like GTPases, including the Rab GTPases; for example, the
      equivalent residues in Rab5 are Ser(29) and Ala(30). The present study builds on
      earlier biochemical characterizations of the Rab5 mutants containing
      substitutions at Ala(30) and provides a comprehensive analysis of the structure
      function relationship of the Rab5 phosphate-binding loop. We have generated 19
      new mutants containing amino acid substitutions at Ser(29) and determined whether
      these Ser(29) mutants, as well as the Ala(30) mutants, remain able to stimulate
      the endocytosis of horseradish peroxidase in baby hamster kidney cells. A total
      of 11 mutants lose the activity of stimulating endocytosis. Of these 11 mutants,
      9 are defective in membrane association. In contrast, 27 mutants remain able to
      stimulate endocytosis. Five of them induce a novel cellular phenotype: cell
      rounding and detachment from culture dishes. They also induce super-large early
      endosomes such as the constitutively activated Rab5:Q79L mutant. Biochemical
      results suggest that the constitutive activation of Rab5 requires an increased
      nucleotide exchange rate and/or decreased GTPase activity. This study establishes
      functional significance for the phosphate-binding loop of Rab5 and shows that
      mutations in this region lead to either a loss-of-function or a gain-of-function
      phenotype, indicating a structure-function relationship distinct from that of
      Ras.

PMID- 11311131
TI  - Involvement of Hic-5 in platelet activation: integrin alphaIIbbeta3-dependent
      tyrosine phosphorylation and association with proline-rich tyrosine kinase 2.
AB  - Hic-5 and paxillin, members of the LIM protein family, have been shown to be
      localized in focal adhesion and to have a role in integrin-mediated signalling.
      In the present study we examined the involvement of Hic-5 in human platelet
      activation: platelets express Hic-5 but not paxillin, whereas human umbilical
      vein vascular endothelial cells and MEG-01 cells express mainly paxillin. When
      platelets were stimulated with thrombin, collagen or the stable thromboxane A(2)
      analogue U46619, Hic-5 was markedly tyrosine-phosphorylated, in a manner
      dependent on integrin alphaIIbbeta3-mediated aggregation. In addition, direct
      activation of protein kinase C with PMA resulted in tyrosine phosphorylation of
      Hic-5 only when platelets were fully aggregated with the exogenous addition of
      fibrinogen. Furthermore, PMA-induced Hic-5 tyrosine phosphorylation was also
      observed when platelets adhered to immobilized fibrinogen. In studies on
      immunoprecipitation and immunodepletion, Hic-5 seemed to associate with proline
      rich tyrosine kinase 2 (Pyk2) but only marginally with focal adhesion kinase.
      When platelets were stimulated with thrombin, both Hic-5 and Pyk2 translocated to
      the cytoskeleton from the cytosol and membrane fractions in a manner dependent on
      alphaIIbbeta3-mediated aggregation. Finally, on stimulation with PMA, Hic-5, as
      well as Pyk2, translocated to the cell periphery, where a meshwork of actin
      filaments assembled after adhesion to immobilized fibrinogen. Our results suggest
      that Hic-5 might be important in platelet aggregation and adhesion, in a manner
      dependent on alphaIIbbeta3-mediated outside-in signalling, through association
      with Pyk2.

PMID- 11311132
TI  - Cytoplasmic interactions between phospholamban residues 1-20 and the calcium
      activated ATPase of the sarcoplasmic reticulum.
AB  - Phospholamban regulates the activity of the calcium-activated ATPase (CaATPase)
      of cardiac sarcoplasmic reticulum. Equilibrium fluorescence studies have shown
      that the N-terminal cytoplasmic region of phospholamban (residues 1-20, domain 1)
      causes a decrease in the intrinsic tryptophan fluorescence of the CaATPase. The
      interaction of phospholamban residues 1-20 with the CaATPase also results in
      spectral changes for the extrinsic chromophore FITC covalently attached to the
      cytoplasmic region of the calcium pump. The fluorescence changes for both
      reporter groups correlate with a dissociation constant of approximately 40 microM
      for the complex between phospholamban residues 1-20 and the CaATPase. Complex
      formation is notably weaker when phospholamban 1-20 is titrated into the CaATPase
      in the presence of calcium, with altered conformational effects resulting from
      binding. The interaction of domain 1 of phospholamban with the CaATPase is also
      reduced upon phosphorylation of phospholamban 1-20 at Ser-16. This region of
      phospholamban 1-20 is shown by isotope-edited NMR study to be involved in
      interaction with the CaATPase. Binding of the phosphorylated peptide is not
      abolished, however, indicating that phospholamban 1-20 remains associated with
      the CaATPase even after phosphorylation. The data provide direct evidence for the
      interaction between the cytoplasmic regions of phospholamban and the pump, and
      are discussed in the context of the mechanism for inhibition of cardiac CaATPase
      activity by phospholamban.

PMID- 11311133
TI  - Characterization of PHEX endopeptidase catalytic activity: identification of
      parathyroid-hormone-related peptide107-139 as a substrate and osteocalcin, PPi
      and phosphate as inhibitors.
AB  - Mutations in the PHEX gene (phosphate-regulating gene with homologies to
      endopeptidases on the X chromosome) are responsible for X-linked
      hypophosphataemia, and studies in the Hyp mouse model of the human disease
      implicate the gene product in the regulation of renal phosphate (P(i))
      reabsorption and bone mineralization. Although the mechanism for PHEX action is
      unknown, structural homologies with members of the M13 family of endopeptidases
      suggest a function for PHEX protein in the activation or degradation of peptide
      factors involved in the control of renal P(i) transport and matrix
      mineralization. To determine whether PHEX has endopeptidase activity, we
      generated a recombinant soluble, secreted form of human PHEX (secPHEX) and tested
      the activity of the purified protein with several peptide substrates, including a
      variety of bone-related peptides. We found that parathyroid-hormone-related
      peptide(107-139) is a substrate for secPHEX and that the enzyme cleaves at three
      positions within the peptide, all located at the N-terminus of aspartate
      residues. Furthermore, we show that osteocalcin, PP(i) and P(i), all of which are
      abundant in bone, are inhibitors of secPHEX activity. Inhibition of secPHEX
      activity by osteocalcin was abolished in the presence of Ca(2+). We suggest that
      PHEX activity and mineralization may be controlled in vivo by PP(i)/P(i) and
      Ca(2+) and, in the latter case, the regulation requires the participation of
      osteocalcin.

PMID- 11311134
TI  - Cloning, expression and localization of human BM88 shows that it maps to
      chromosome 11p15.5, a region implicated in Beckwith-Wiedemann syndrome and
      tumorigenesis.
AB  - Porcine BM88 is a neuron-specific protein that enhances neuroblastoma cell
      differentiation in vitro and may be involved in neuronal differentiation in vivo.
      Here we report the identification, by Western blotting, of homologous proteins in
      human and mouse brain and the isolation of their respective cDNAs. Several human
      and mouse clones were identified in the EST database using porcine BM88 cDNA as a
      query. A human and a mouse EST clone were chosen for sequencing and were found
      both to predict a protein of 149 amino acids, with 79.9% reciprocal identity, and
      76.4% and 70.7% identities to the porcine protein, respectively. This indicated
      that the clones corresponded to the human and mouse BM88 homologues. In vitro
      expression in a cell-free system as well as transient expression in COS7 cells
      yielded polypeptide products that were recognized by anti-BM88 antibodies and
      were identical in size to the native BM88 protein. Northern-blot analysis showed
      a wide distribution of the gene in human brain whereas immunohistochemistry on
      human brain sections demonstrated that the expression of BM88 is confined to
      neurons. The initial mapping assignment of human BM88 to chromosome 11p15.5, a
      region implicated in Beckwith-Wiedemann syndrome and tumorigenesis, was retrieved
      from the UniGene database maintained at the National Centre for Biotechnology
      Information (NCBI, Bethesda, MD, U.S.A.). We confirmed this localization by
      performing fluorescence in situ hybridization on BM88-positive cosmid clones
      isolated from a human genomic library. These results suggest that BM88 may be a
      candidate gene for genetic disorders associated with alterations at 11p15.5.

PMID- 11311135
TI  - Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different
      domains.
AB  - Heterodimeric amino acid transporters are comprised of a type-II membrane protein
      named the heavy chain (4F2hc or rBAT) that may associate with a number of
      different polytopic membrane proteins, called light chains. It is thought that
      the heavy chain is mainly involved in the trafficking of the complex to the
      plasma membrane, whereas the transport process itself is catalysed by the light
      chain. The 4F2 heavy chain (4F2hc) associates with at least six different light
      chains to induce distinct amino acid-transport activites. To test if the light
      chains are specifically recognized and to identify domains involved in the
      recognition of light chains, C-terminally truncated mutants of 4F2hc were
      constructed and co-expressed with the light chains LAT1, LAT2 and y(+)LAT2. The
      truncated isoform T1, comprised of only 133 amino acids that form the cytosolic N
      terminus and the transmembrane helix, displayed only a slight reduction in its
      ability to promote LAT1 expression at the membrane surface compared with the 529
      amino acid wild-type 4F2hc protein. Co-expression of increasingly larger 4F2hc
      mutants caused a delayed translocation of LAT1. In contrast to the weak effects
      of 4F2hc truncations on LAT1 expression, surface expression of LAT2 and y(+)LAT2
      was almost completely lost with all truncated heavy chains. Co-expression of LAT1
      together with the other light chains did not result in displacement of LAT2 and
      y(+)LAT2. The results suggest that extracellular domains of the heavy chain are
      responsible mainly for recognition of light chains other than LAT1 and that the
      extracellular domain ensures proper translocation to the plasma membrane.

PMID- 11311136
TI  - Transport of lactate and pyruvate in the intraerythrocytic malaria parasite,
      Plasmodium falciparum.
AB  - The mature, intraerythrocytic form of the human malaria parasite, Plasmodium
      falciparum, is reliant on glycolysis for its energetic requirements. It produces
      large quantities of lactic acid, which have to be removed from the parasite's
      cytosol to maintain the cell's integrity and metabolic viability. Here we show
      that the monocarboxylates lactate and pyruvate are both transported across the
      parasite's plasma membrane via a H(+)/monocarboxylate symport process that is
      saturable and inhibited by the bioflavonoid phloretin. The results provide direct
      evidence for the presence at the parasite surface of a H(+)-coupled
      monocarboxylate transporter with features in common with members of the MCT
      (monocarboxylate transporter) family of higher eukaryotes.

PMID- 11311137
TI  - Agonist-promoted trafficking of human bradykinin receptors: arrestin- and dynamin
      independent sequestration of the B2 receptor and bradykinin in HEK293 cells.
AB  - In this study, we analysed the agonist-promoted trafficking of human B(2) (B(2)R)
      and B(1) (B(1)R) bradykinin (BK) receptors using wild-type and green fluorescent
      protein (GFP)-tagged receptors in HEK293 cells. B(2)R was sequestered to a major
      extent upon exposure to BK, as determined by the loss of cell-surface B(2)R using
      radioligand binding and by imaging of B(2)R-GFP using laser-scanning confocal
      fluorescence microscopy. Concurrent BK sequestration was revealed by the
      appearance of acid-resistant specific BK receptor binding. The same techniques
      showed that B(1)R was sequestered to a considerably lesser extent upon binding of
      des-Arg(10)-kallidin. B(2)R sequestration was rapid (half-life approximately 5
      min) and reached a steady-state level that was significantly lower than that of
      BK sequestration. B(2)R sequestration was minimally inhibited by K44A dynamin
      (22.4+/-3.7%), and was insensitive to arrestin-(319-418), which are dominant
      negative mutants of dynamin I and beta-arrestin respectively. Furthermore, the
      B(2)R-mediated sequestration of BK was completely insensitive to both mutants, as
      was the association of BK with a caveolae-enriched fraction of the cells. On the
      other hand, agonist-promoted sequestration of the beta(2)-adrenergic receptor was
      dramatically inhibited by K44A dynamin (81.2+/-16.3%) and by arrestin-(319-418)
      (36.9+/-4.4%). Our results show that B(2)R is sequestered to a significantly
      greater extent than is B(1)R upon agonist treatment in HEK293 cells. Furthermore,
      B(2)R appears to be recycled in the process of sequestering BK, and this process
      occurs in a dynamin- and beta-arrestin-independent manner and, at least in part,
      involves caveolae.

PMID- 11311138
TI  - Monocyte chemoattractant protein 1 causes differential signalling mediated by
      proline-rich tyrosine kinase 2 in THP-1 cells.
AB  - Monocyte chemoattractant protein 1 (MCP-1) has a crucial role in atherogenesis
      and inflammation. However, MCP-1-mediated signalling pathways in monocytes have
      not been fully elucidated. In the present study we investigated the role of
      tyrosine kinases such as proline-rich tyrosine kinase 2 (Pyk2) in MCP-1-mediated
      signal transduction in the monocytic cell line THP-1. Pyk2 was tyrosine
      phosphorylated very quickly after stimulation with MCP-1. We found that Lyn, Shc
      and paxillin were also tyrosine phosphorylated by MCP-1. We examined the
      association of these molecules by immunoprecipitation and immunoblot analysis.
      The association of Pyk2 with Lyn was dependent on stimulation with MCP-1 and on
      tyrosine phosphorylation of Pyk2. Phosphorylation of p38 was also dependent on
      tyrosine phosphorylation of Pyk2. However, the association of Pyk2 with paxillin
      and Grb2 was not affected by stimulation with MCP-1. Phosphorylation of ERK
      (extracellular-signal-regulated protein kinase) was not affected by
      overexpression of kinase-negative Pyk2. Our results indicate that Pyk2 forms a
      complex with paxillin, Grb2 and Lyn in THP-1 cells. However, Pyk2 is not always
      involved in MCP-1-mediated signalling pathways.

PMID- 11311139
TI  - Oxidative stress impairs insulin but not platelet-derived growth factor
      signalling in 3T3-L1 adipocytes.
AB  - Activation of phosphatidylinositol 3-kinase (PI 3-kinase) is a common event in
      both insulin and platelet-derived growth factor (PDGF) signalling, but only
      insulin activates this enzyme in the high-speed pellet (HSP), and induces GLUT4
      translocation. Recently, we have demonstrated that exposure of 3T3-L1 adipocytes
      to oxidative stress impairs insulin-stimulated GLUT4 translocation and glucose
      transport, associated with impaired PI 3-kinase translocation and activation in
      the HSP [Tirosh, Potashnik, Bashan and Rudich (1999) J. Biol. Chem. 274, 10595
      10602]. In this study the effect of a 2 h exposure to approximately 30 microM
      H(2)O(2) on insulin versus PDGF-BB signalling and metabolic effects was compared.
      PDGF-stimulated p85-associated PI 3-kinase activity in total cell lysates, as
      well as co-precipitation of the PDGF receptor, were unaffected by oxidative
      stress. Additionally, the increase in p85 association with the plasma-membrane
      lawns by PDGF remained intact following oxidation, whereas the insulin effect was
      decreased. PDGF significantly increased protein kinase B (PKB) activity in early
      differentiated cells, and that of p70 S6-kinase in both early and fully
      differentiated 3T3-L1 adipocytes. Following oxidation the effect of PDGF on PKB
      and p70 S6-kinase activation remained intact, whereas significant inhibition of
      insulin-stimulated activation of those enzymes was observed. In accordance, in
      both early and fully differentiated cells, oxidative stress completely blunted
      insulin- but not PDGF-stimulated protein synthesis. In conclusion, oxidative
      stress impairs insulin, but not PDGF, signalling and metabolic actions in both
      early and fully differentiated 3T3-L1 adipocytes. This emphasizes compartment
      specific activation of PI 3-kinase as an oxidation-sensitive step specifically
      leading to insulin resistance.

PMID- 11311140
TI  - Lysosomal phospholipase A1 in Trypanosoma cruzi: an enzyme with a possible role
      in the pathogenesis of Chagas' disease.
AB  - We found that, as in African trypanosomes, endogenous phospholipase A(1) (Plase
      A(1)) activity can catalyse extensive deacylation of phospholipids upon cell
      death in all life stages of Trypanosoma cruzi. A major lysosomal Plase A(1) was
      purified and characterized. The enzyme products can explain the lesions
      surrounding degenerating T. cruzi cells in host tissues. Thus Plase A(1) emerges
      as a target to block pathogenesis in trypanosomal infections.

PMID- 11311141
TI  - Sound attenuation of polymerizing actin reflects supramolecular structures:
      viscoelastic properties of actin gels modified by cytochalasin D, profilin and
      alpha-actinin.
AB  - Polymerization and depolymerization of cytoskeletal elements maintaining
      cytoplasmic stiffness are key factors in the control of cell crawling. Rheometry
      is a significant tool in determining the mechanical properties of the single
      elements in vitro. Viscoelasticity of gels formed by these polymers strongly
      depends on both the length and the associations of the filaments (e.g.
      entanglements, annealings and side-by-side associations). Ultrasound attenuation
      is related to viscosity, sound velocity and supramolecular structures in the
      sample. In combination with a small glass fibre (2 mm x 50 microm), serving as a
      viscosity sensor, an acoustic microscope was used to measure the elasticity and
      acoustic attenuation of actin solutions. Changes in acoustic attenuation of
      polymerizing actin by far exceed the values expected from calculations based on
      changes in viscosity and sound velocity. During the lag-phase of actin
      polymerization, attenuation slightly decreases, depending on actin concentration.
      After the half-maximum viscosity is accomplished and elasticity turns into steady
      state, attenuation distinctly rises. Changes in ultrasound attenuation depend on
      actin concentration, and they are modulated by the addition of alpha-actinin,
      cytochalasin D and profilin. Thus absorption and scattering of sound on the
      polymerization of actin is related to the packing density of the actin net,
      entanglements and the length of the actin filaments. Shortening of actin
      filaments by cytochalasin D was also confirmed by electron micrographs and
      falling-ball viscosimetry. In addition to viscosity and elasticity, the
      attenuation of sound proved to be a valuable parameter in characterizing actin
      polymerization and the supramolecular associations of F-actin.

PMID- 11311142
TI  - Determination of interaction sites of phospholipase D1 for RhoA.
AB  - Phospholipase D (PLD) is regulated by many factors, including protein kinase C
      (PKC) and small G-proteins of the Rho and ADP-ribosylation factor families.
      Previous studies revealed that the interaction site of human PLD(1) for RhoA is
      located in its C-terminus, but the exact locus has not been determined. The
      purpose of the present study was to determine the interaction site of rat PLD(1)
      (rPLD(1)) with RhoA. Selection with phage display of different peptides of
      rPLD(1) confirmed that GTP-bound RhoA interacted with a site in the amino acid
      sequence 873-1024 at the C-terminus of rPLD(1). RhoA also associated with this
      peptide in a GTP-dependent manner in COS-7 cell lysates and the peptide inhibited
      RhoA stimulation of PLD activity in membranes from COS-7 cells expressing
      rPLD(1). A series of alanine mutations of non-conserved residues were made in
      this sequence, and the enzymes were expressed in COS-7 cells and checked for
      responses to activation of PKC, which interacts with the N-terminus of PLD(1),
      and also to the constitutively active V14RhoA. Mutations in the C-terminus of
      rPLD(1) (K946A, V950A, R955A and K962A) caused partial loss of V14RhoA
      stimulation, and double mutations (K946A/K962A, K946A/V950A and K962A/V950A)
      caused an almost total loss. Co-immunoprecipitation studies also showed that the
      mutated forms of rPLD(1) described above failed to bind V14RhoA compared with
      wild-type rPLD(1), whereas rPLD(1) with mutations outside the region K946-K962
      bound V14RhoA normally. It is concluded that basic amino acids in a restricted C
      terminal region of rPLD(1) are important for binding of RhoA and its activation
      of PLD activity.

PMID- 11311143
TI  - Occurrence of paradoxical or sustained control by an enzyme when overexpressed:
      necessary conditions and experimental evidence with regard to hepatic
      glucokinase.
AB  - It is widely assumed that the control coefficient of an enzyme on pathway flux
      decreases as the concentration of enzyme increases. However, it has been shown
      [Kholodenko and Brown (1996) Biochem. J. 314, 753-760] that enzymes with
      sigmoidal kinetics can maintain or even gain control with an increase in enzyme
      activity or concentration. This has been described as 'paradoxical control'. Here
      we formulate the general requirements for allosteric enzyme kinetics to display
      this behaviour. We show that a necessary condition is that the Hill coefficient
      of the enzyme should increase with an increase in substrate concentration or
      decrease with an increase in product concentration. We also describe the
      necessary and sufficient requirements for the occurrence of paradoxical control
      in terms of the flux control coefficients and the derivatives of the
      elasticities. The derived expression shows that the higher the control
      coefficient of an allosteric enzyme, the more likely it is that the pathway will
      display this behaviour. Control of pathway flux is generally shared between a
      large number of enzymes and therefore the likelihood of observing sustained or
      increased control is low, even if the kinetic parameters are in the most
      favourable range to generate the phenomenon. We show that hepatic glucokinase,
      which has a very high flux control coefficient and displays sigmoidal behaviour
      within the hepatocyte in situ as a result of interaction with a regulatory
      protein, displays sustained or increased control over an extended range of enzyme
      concentrations when the regulatory protein is overexpressed.

PMID- 11311144
TI  - Involvement of mitogen-activated protein kinase activation in the signal
      transduction pathways of the soya bean oxidative burst.
AB  - The oxidative burst constitutes one of the most rapid defence responses
      characterized in the Plant Kingdom. We have observed that four distinct elicitors
      of the soya bean oxidative burst activate kinases of masses approximately 44 kDa
      and approximately 47 kDa. Evidence that these kinases regulate production of
      reactive oxygen species include: (i) their rapid activation by oxidative burst
      elicitors, (ii) their tight temporal correlation between activation/deactivation
      of the kinases and activation/deactivation of the oxidative burst, (iii) the
      identical pharmacological profile of kinase activation and oxidant production for
      13 commonly used inhibitors, and (iv) the autologous activation of both kinases
      and oxidant production by calyculin A and cantharidin, two phosphatase
      inhibitors. Immunological and biochemical studies reveal that the activated 44
      kDa and 47 kDa kinases are mitogen-activated protein (MAP) kinase family members.
      The kinases prefer myelin basic protein as a substrate, and they phosphorylate
      primarily on threonine residues. The kinases are themselves phosphorylated on
      tyrosine residues, and this phosphorylation is required for activity. Finally,
      both kinases are recognized by an antibody against activated MAP kinase
      immediately after (but not before) cell stimulation by elicitors. Based on these
      and other observations, a preliminary sequence of signalling steps linking
      elicitor stimulation, kinase activation and Ca(2+) entry, to initiation of
      oxidant production, is proposed.

PMID- 11311145
TI  - Mammalian inositol polyphosphate 5-phosphatase II can compensate for the absence
      of all three yeast Sac1-like-domain-containing 5-phosphatases.
AB  - Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] plays a complex role in
      generating intracellular signalling molecules, and also in regulating actin
      binding proteins, vesicular trafficking and vacuolar fusion. Four inositol
      polyphosphate 5-phosphatases (hereafter called 5-phosphatases) have been
      identified in Saccharomyces cerevisiae: Inp51p, Inp52p, Inp53p and Inp54p. Each
      enzyme contains a 5-phosphatase domain which hydrolyses PtdIns(4,5)P(2), forming
      PtdIns4P, while Inp52p and Inp53p also express a polyphosphoinositide phosphatase
      domain within the Sac1-like domain. Disruption of any two yeast 5-phosphatases
      containing a Sac1-like domain results in abnormalities in actin polymerization,
      plasma membrane, vacuolar morphology and bud-site selection. Triple null mutant 5
      phosphatase strains are non-viable. To investigate the role of PtdIns(4,5)P(2) in
      mediating the phenotype of double and triple 5-phosphatase null mutant yeast, we
      determined whether a mammalian PtdIns(4,5)P(2) 5-phosphatase, 5-phosphatase II,
      which lacks polyphosphoinositide phosphatase activity, could correct the
      phenotype of triple 5-phosphatase null mutant yeast and restore cellular
      PtdIns(4,5)P(2) levels to near basal values. Mammalian 5-phosphatase II expressed
      under an inducible promoter corrected the growth, cell wall, vacuolar and actin
      polymerization defects of the triple 5-phosphatase null mutant yeast strains.
      Cellular PtdIns(4,5)P(2) levels in various 5-phosphatase double null mutant
      strains demonstrated significant accumulation (4.5-, 3- and 2-fold for
      Deltainp51Deltainp53, Deltainp51Deltainp52 and Deltainp52Deltainp53 double null
      mutants respectively), which was corrected significantly following 5-phosphatase
      II expression. Collectively, these studies demonstrate the functional and
      cellular consequences of PtdIns(4,5)P(2) accumulation and the evolutionary
      conservation of function between mammalian and yeast PtdIns(4,5)P(2) 5
      phosphatases.

PMID- 11311146
TI  - Rat peptide methionine sulphoxide reductase: cloning of the cDNA, and down
      regulation of gene expression and enzyme activity during aging.
AB  - Peptide methionine sulphoxide reductase (PMSR, EC 1.8.4.6), the msrA or pmsR gene
      product, is a ubiquitous enzyme catalysing the reduction of methionine sulphoxide
      to methionine in proteins. Decreased expression and/or activity of the PMSR with
      age could explain, at least in part, the accumulation of oxidized protein
      observed upon aging. To test this hypothesis, the rat pmsR cDNA was cloned and
      sequenced. The recombinant protein was expressed, its catalytic activity checked
      with a synthetic substrate and polyclonal antibodies were raised against
      recombinant PMSR. The expression of the pmsR gene and protein as well as its
      catalytic activity were then analysed as a function of age in the rat brain and
      in two organs that express the most PMSR, liver and kidney. It appears that pmsR
      gene expression decreases with age in liver and kidney as early as 18 months,
      whereas protein level and protein activity are reduced in the three organs at the
      very end of the life of the rat (26 months). These results suggest that the down
      regulation of PMSR can contribute to the accumulation of oxidized protein that
      has been associated with the aging process.

PMID- 11311147
TI  - Suramin and the suramin analogue NF307 discriminate among calmodulin-binding
      sites.
AB  - Calmodulin-binding sites on target proteins show considerable variation in
      primary sequence; hence compounds that block the access of calmodulin to these
      binding sites may be more selective than compounds that inactivate calmodulin.
      Suramin and its analogue NF307 inhibit the interaction of calmodulin with the
      ryanodine receptor. We have investigated whether inhibition of calmodulin binding
      to target proteins is a general property of these compounds. Suramin inhibited
      binding of [(125)I]calmodulin to porcine brain membranes and to sarcoplasmic
      reticulum from skeletal muscle (IC(50)=4.9+/-1.2 microM and 19.9+/-1.8 microM,
      respectively) and blocked the cross-linking of [(125)I]calmodulin to some, but
      not all, target proteins in brain membranes by [(125)I]calmodulin. Four
      calmodulin-binding proteins were purified [ryanodine receptor-1 (RyR1) from
      rabbit skeletal muscle, neuronal NO synthase (nNOS) from Sf9 cells, G-protein
      betagamma dimers (Gbetagamma) from porcine brain and a glutathione S-transferase
      fusion protein comprising the C-terminal calmodulin-binding domain of the
      metabotropic glutamate receptor 7A (GST-CmGluR7A) from bacterial lysates]. Three
      of the proteins employed (Gbetagamma, GST-CmGluR7A and RyR1) display a comparable
      affinity for calmodulin (in the range of 50-70 nM). Nevertheless, suramin and
      NF307 only blocked the binding of Gbetagamma and RyR1 to calmodulin-Sepharose. In
      contrast, the association of GST-CmGluR7A and nNOS was not impaired, whereas
      excess calmodulin uniformly displaced all proteins from the matrix. Thus suramin
      and NF307 are prototypes of a new class of calmodulin antagonists that do not
      interact directly with calmodulin but with calmodulin-recognition sites. In
      addition, these compounds discriminate among calmodulin-binding motifs.

PMID- 11311148
TI  - Catalytic mechanism of a family 3 beta-glucosidase and mutagenesis study on
      residue Asp-247.
AB  - A family 3 beta-glucosidase (EC 3.2.1.21) from Flavobacterium meningosepticum has
      been cloned and overexpressed. The mechanistic action of the enzyme was probed by
      NMR spectroscopy and kinetic investigations, including substrate reactivity,
      secondary kinetic isotope effects and inhibition studies. The stereochemistry of
      enzymic hydrolysis was identified as occurring with the retention of an anomeric
      configuration, indicating a double-displacement reaction. Based on the k(cat)
      values with a series of aryl glucosides, a Bronsted plot with a concave-downward
      shape was constructed. This biphasic behaviour is consistent with a two-step
      mechanism involving the formation and breakdown of a glucosyl-enzyme
      intermediate. The large Bronsted constant (beta=-0.85) for the leaving-group
      dependent portion (pK(a) of leaving phenols >7) indicates substantial bond
      cleavage at the transition state. Secondary deuterium kinetic isotope effects
      with 2,4-dinitrophenyl beta-D-glucopyanoside, o-nitrophenyl beta-D-glucopyanoside
      and p-cyanophenyl beta-D-glucopyanoside as substrates were 1.17+/-0.02, 1.19+/
      0.02 and 1.04+/-0.02 respectively. These results support an S(N)1-like mechanism
      for the deglucosylation step and an S(N)2-like mechanism for the glucosylation
      step. Site-directed mutagenesis was also performed to study essential amino acid
      residues. The activities (k(cat)/K(m)) of the D247G and D247N mutants were 30000-
      and 200000-fold lower respectively than that of the wild-type enzyme, whereas the
      D247E mutant retained 20% of wild-type activity. These results indicate that Asp
      247 is an essential amino acid. It is likely that this residue functions as a
      nucleophile in the reaction. This conclusion is supported by the kinetics of the
      irreversible inactivation of the wild-type enzyme by conduritol-B-epoxide,
      compared with the much slower inhibition of the D247E mutant and the lack of
      irreversible inhibition of the D247G mutant.

PMID- 11311149
TI  - Structure-function studies of human deoxyhypusine synthase: identification of
      amino acid residues critical for the binding of spermidine and NAD.
AB  - Deoxyhypusine synthase catalyses the first step in the biosynthesis of hypusine
      [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. The crystal structure of human
      deoxyhypusine synthase in complex with NAD revealed four NAD-binding sites per
      enzyme tetramer, and led to a prediction of the spermidine-binding pocket. We
      have replaced each of the seven amino acid residues at the predicted spermidine
      binding site, and eleven residues that contact NAD, on an individual basis with
      alanine. Of the amino acid residues at the spermidine site, substitution of Asp
      243, Trp-327, His-288, Asp-316 or Glu-323 with alanine caused an almost complete
      loss of spermidine binding and enzyme activity; only the mutation Tyr-305-->Ala
      showed partial binding and activity. His-288-->Ala was also deficient in terms of
      binding NAD. NAD binding was significantly reduced in all of the NAD-site mutant
      enzymes, except for Glu-137-->Ala, which showed a normal binding of NAD, but was
      totally lacking in spermidine binding. Of the NAD-site mutant enzymes, Asp-342-
      >Ala, Asp-313-->Ala and Asp-238-->Ala displayed the lowest binding of NAD. These
      enzymes and His-288Ala also showed a reduced binding of spermidine, presumably
      because spermidine binding is dependent on NAD. These findings permit the
      positive identification of amino acid residues critical for binding of spermidine
      and NAD, and provide a new insight into the complex molecular interactions
      involved in the deoxyhypusine synthase reaction.

PMID- 11311150
TI  - Characterization of membrane-localized and cytosolic Rac-GTPase-activating
      proteins in human neutrophil granulocytes: contribution to the regulation of
      NADPH oxidase.
AB  - We have investigated the intracellular localization and molecular identity of Rac
      GTPase-activating proteins (Rac-GAPs) in human neutrophils. Immunoblot analysis
      detected the presence of both p190RhoGAP and Bcr mainly in the cytosol. An
      overlay assay performed with [gamma-(32)P]GTP-bound Rac revealed dominant GAP
      activity related to a 50 kDa protein both in the membrane and cytosol. This
      activity could be identified by Western blotting and immunoprecipitation with
      specific antibody directed against the GAP domain of p50RhoGAP. Using a
      semirecombinant or fully purified cell-free activation assay of the Rac-activated
      enzyme NADPH oxidase, we demonstrated the regulatory effect of both the membrane
      localized and soluble GAPs. We suggest that in neutrophil granulocytes Rac-GAPs
      have redundant function and represent suitable targets for both the up-regulation
      and down-regulation of the NADPH oxidase.

PMID- 11311151
TI  - A neutral sphingomyelinase resides in sphingolipid-enriched microdomains and is
      inhibited by the caveolin-scaffolding domain: potential implications in tumour
      necrosis factor signalling.
AB  - Sphingomyelinases hydrolyse sphingomyelin to ceramide, a process involved in
      signal-transduction routes leading to apoptosis and various other cellular
      responses. In the present study, we investigated the sphingomyelinase content of
      caveolae, invaginated plasma-membrane microdomains that contain a variety of
      signalling molecules. These structures are highly enriched in sphingomyelin as
      well as in ceramide, which suggests that metabolism of these lipids might, to
      some extent, occur locally. By cell fractionation, we demonstrate that, in
      addition to a previously reported minute amount of acidic sphingomyelinase
      activity, a substantial amount of neutral sphingomyelinase activity resides in
      caveolae of human skin fibroblasts. This caveolar neutral sphingomyelinase
      activity was also detected in Niemann-Pick disease type A fibroblasts, which are
      completely devoid of functional acidic sphingomyelinase. Neutral (but not acidic)
      sphingomyelinase activity was specifically inhibited by a peptide that
      corresponds to the scaffolding domain of caveolin, which suggests a direct
      molecular interaction between the two proteins. In addition, this finding implies
      a cytosolic orientation of the caveolar neutral sphingomyelinase. Interestingly,
      stimulation of fibroblasts with tumour necrosis factor alpha (TNFalpha) resulted
      in a partial shift of its p55 receptor to caveolin-enriched membrane fractions
      and the appearance of caveolin-sensitive neutral sphingomyelinase activity in the
      non-caveolar fractions. These results suggest that (part of) the presently
      identified caveolar neutral sphingomyelinase activity is involved in TNFalpha
      signalling.

PMID- 11311152
TI  - In vitro studies of amyloid beta-protein fibril assembly and toxicity provide
      clues to the aetiology of Flemish variant (Ala692-->Gly) Alzheimer's disease.
AB  - In a Flemish kindred, an Ala(692)-->Gly amino acid substitution in the amyloid
      beta-protein precursor (AbetaPP) causes a form of early-onset Alzheimer's disease
      (AD) which displays prominent amyloid angiopathy and unusually large senile
      plaque cores. The mechanistic basis of this Flemish form of AD is unknown.
      Previous in vitro studies of amyloid beta-protein (Abeta) production in HEK-293
      cells transfected with cDNA encoding Flemish AbetaPP have shown that full-length
      [Abeta(1-40)] and truncated [Abeta(5-40) and Abeta(11-40)] forms of Abeta are
      produced. In an effort to determine how these peptides might contribute to the
      pathogenesis of the Flemish disease, comparative biophysical and neurotoxicity
      studies were performed on wild-type and Flemish Abeta(1-40), Abeta(5-40) and
      Abeta(11-40). The results revealed that the Flemish amino acid substitution
      increased the solubility of each form of peptide, decreased the rate of formation
      of thioflavin-T-positive assemblies, and increased the SDS-stability of peptide
      oligomers. Although the kinetics of peptide assembly were altered by the Ala(21)-
      >Gly substitution, all three Flemish variants formed fibrils, as did the wild
      type peptides. Importantly, toxicity studies using cultured primary rat cortical
      cells showed that the Flemish assemblies were as potent a neurotoxin as were the
      wild-type assemblies. Our results are consistent with a pathogenetic process in
      which conformational changes in Abeta induced by the Ala(21)-->Gly substitution
      would facilitate peptide adherence to the vascular endothelium, creating nidi for
      amyloid growth. Increased peptide solubility and assembly stability would favour
      formation of larger deposits and inhibit their elimination. In addition,
      increased concentrations of neurotoxic assemblies would accelerate neuronal
      injury and death.

PMID- 11311153
TI  - The relationship of the factor V Leiden mutation or the deletion-deletion
      polymorphism of the angiotensin converting enzyme to postoperative thromboembolic
      events following total joint arthroplasty.
AB  - BACKGROUND: Although all patients undergoing total joint arthroplasty are
      subjected to similar risk factors that predispose to thromboembolism, only a
      subset of patients develop this complication. The objective of this study was to
      determine whether a specific genetic profile is associated with a higher risk of
      developing a postoperative thromboembolic complication. Specifically, we examined
      if the Factor V Leiden (FVL) mutation or the deletion polymorphism of the
      angiotensin-converting enzyme (ACE) gene increased a patient's risk for
      postoperative thromboembolic events. The FVL mutation has been associated with an
      increased risk of idiopathic thromboembolism and the deletion polymorphism of the
      ACE gene has been associated with increased vascular tone, attenuated
      fibrinolysis and increased platelet aggregation. METHODS: The presence of these
      genetic profiles was determined for 38 patients who had a postoperative
      symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control
      patients without thrombosis using molecular biological techniques. RESULTS: The
      Factor V Leiden mutation was present in none of the 38 experimental patients and
      in 3% or 8 of the 241 controls (p = 0.26). Similarly there was no difference
      detected in the distribution of polymorphisms for the ACE gene with the deletion
      deletion genotype present in 36% or 13 of the 38 experimental patients and in 31%
      or 74 of the 241 controls (p = 0.32). CONCLUSIONS: Our results suggest that
      neither of these potentially hypercoaguable states are associated with an
      increased risk of symptomatic thromboembolic events following total hip or knee
      arthroplasty in patients receiving pharmacological thromboprophylaxis.

PMID- 11311154
TI  - Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify
      prospective neurectodermal cell fate in the mouse embryo.
AB  - During gastrulation in the mouse, mesoderm is induced and patterned by secreted
      signaling molecules, giving rise first to primitive erythroblasts and vascular
      endothelial cells. We have demonstrated previously that development of these
      lineages requires a signal(s) secreted from the adjacent primitive endoderm. We
      now show that Indian hedgehog (Ihh) is a primitive endoderm-secreted signal that
      alone is sufficient to induce formation of hematopoietic and endothelial cells.
      Strikingly, as seen with primitive endoderm, Ihh can respecify prospective neural
      ectoderm (anterior epiblast) along hematopoietic and endothelial (posterior)
      lineages. Downstream targets of the hedgehog signaling pathway (the genes
      encoding patched, smoothened and Gli1) are upregulated in anterior epiblasts
      cultured in the presence of Ihh protein, as is Bmp4, which may mediate the
      effects of Ihh. Blocking Ihh function in primitive endoderm inhibits activation
      of hematopoiesis and vasculogenesis in the adjacent epiblast, suggesting that Ihh
      is an endogenous signal that plays a key role in the development of the earliest
      hemato-vascular system. To our knowledge, these are the earliest functions for a
      hedgehog protein in post-implantation development in the mouse embryo.

PMID- 11311155
TI  - The dermomyotome dorsomedial lip drives growth and morphogenesis of both the
      primary myotome and dermomyotome epithelium.
AB  - The cellular and molecular mechanisms that govern early muscle patterning in
      vertebrate development are unknown. The earliest skeletal muscle to organize, the
      primary myotome of the epaxial domain, is a thin sheet of muscle tissue that
      expands in each somite segment in a lateral-to-medial direction in concert with
      the overlying dermomyotome epithelium. Several mutually contradictory models have
      been proposed to explain how myotome precursor cells, which are known to reside
      within the dermomyotome, translocate to the subjacent myotome layer to form this
      first segmented muscle tissue of the body. Using experimental embryology to
      discriminate among these models, we show here that ablation of the dorsomedial
      lip (DML) of the dermomyotome epithelium blocks further primary myotome growth
      while ablation of other dermomyotome regions does not. Myotome growth and
      morphogenesis can be restored in a DML-ablated somite of a host embryo by
      transplantation of a second DML from a donor embryo. Chick-quail marking
      experiments show that new myotome cells in such recombinant somites are derived
      from the donor DML and that cells from other regions of the somite are neither
      present nor required. In addition to the myotome, the transplanted DML also gives
      rise to the dermomyotome epithelium overlying the new myotome growth region and
      from which the mesenchymal dermatome will later emerge. These results demonstrate
      that the DML is a cellular growth engine that is both necessary and sufficient to
      drive the growth and morphogenesis of the primary myotome and simultaneously
      drive that of the dermomyotome, an epithelium containing muscle, dermis and
      possibly other potentialities.

PMID- 11311156
TI  - Morphogenetic cell movements in the middle region of the dermomyotome dorsomedial
      lip associated with patterning and growth of the primary epaxial myotome.
AB  - The morphogenetic cell movements responsible for growth and morphogenesis in
      vertebrate embryos are poorly understood. Myotome precursor cells undergo
      myotomal translocation; a key morphogenetic cell movement whereby myotomal
      precursor cells leave the dermomyotome epithelium and enter the subjacent myotome
      layer where myogenic differentiation ensues. The precursors to the embryonic
      epaxial myotome are concentrated in the dorsomedial lip (DML) of the somite
      dermomyotome (W. F. Denetclaw, B. Christ and C. P. Ordahl (1997) Development 124,
      1601-1610), a finding recently substantiated through surgical transplantation
      studies (C. P. Ordahl, E. Berdougo, S. J. Venters and W. F. Denetclaw, Jr (2001)
      Development 128, 1731-1744). Confocal microscopy was used here to analyze the
      location and pattern of myotome cells whose precursors had earlier been labeled
      by fluorescent dye injection into the middle region of the DML, a site that
      maximizes the potential to discriminate among experimental outcomes. Double-dye
      injection experiments conducted at this site demonstrate that cells fated to form
      myotome do not involute around the recurved epithelium of the DML but rather are
      displaced laterally where they transiently intermingle with cells fated to enter
      the central epithelial sheet region of the dermomyotome. Time- and position
      dependent labeling experiments demonstrated that myotome precursor cells
      translocate directly from the middle region of the DML without prior intra
      epithelial 'translational' movements of precursor cells to either the cranial or
      caudal lips of the dermomyotome epithelium, nor were any such translational
      movements evident in these experiments. The morphogenetic cell movements
      demonstrated here to be involved in the directional growth and segmental
      patterning of the myotome and dermomyotome bear interesting similarities with
      those of other morphogenetic systems.

PMID- 11311157
TI  - Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular
      area of the chick embryo.
AB  - Oligodendrocytes are the myelin-forming cells in the central nervous system. In
      the brain, oligodendrocyte precursors arise in multiple restricted foci,
      distributed along the caudorostral axis of the ventricular neuroepithelium. In
      chick embryonic hind-, mid- and caudal forebrain, oligodendrocytes have a
      basoventral origin, while in the rostral fore-brain oligodendrocytes emerge from
      alar territories (Perez Villegas, E. M., Olivier, C., Spassky, N., Poncet, C.,
      Cochard, P., Zalc, B., Thomas, J. L. and Martinez, S. (1999) Dev. Biol. 216, 98
      113). To investigate the respective territories colonized by oligodendrocyte
      progenitor cells that originate from either the basoventral or alar foci, we have
      created a series of quail-chick chimeras. Homotopic chimeras demonstrate clearly
      that, during embryonic development, oligodendrocyte progenitors that emerge from
      the alar anterior entopeduncular area migrate tangentially to invade the entire
      telencephalon, whereas those from the basal rhombomeric foci show a restricted
      rostrocaudal distribution and colonize only their rhombomere of origin.
      Heterotopic chimeras indicate that differences in the migratory properties of
      oligodendroglial cells do not depend on their basoventral or alar ventricular
      origin. Irrespective of their origin (basal or alar), oligodendrocytes migrate
      only short distances in the hindbrain and long distances in the prosencephalon.
      Furthermore, we provide evidence that, in the developing chick brain, all
      telencephalic oligodendrocytes originate from the anterior entopeduncular area
      and that the prominent role of anterior entopeduncular area in telencephalic
      oligodendrogenesis is conserved between birds and mammals.

PMID- 11311158
TI  - The ASYMMETRIC LEAVES2 gene of Arabidopsis thaliana regulates formation of a
      symmetric lamina, establishment of venation and repression of meristem-related
      homeobox genes in leaves.
AB  - The asymmetric leaves2 (as2) mutant of Arabidopsis thaliana generated leaf lobes
      and leaflet-like structures from the petioles of leaves in a bilaterally
      asymmetric manner. Both the delayed formation of the primary vein and the
      asymmetric formation of secondary veins were apparent in leaf primordia of as2
      plants. A distinct midvein, which is the thickest vein and is located in the
      longitudinal center of the leaf lamina of wild-type plants, was often rudimentary
      even in mature as2 leaves. However, several parallel veins of very similar
      thickness were evident in such leaves. The complexity of venation patterns in all
      leaf-like organs of as2 plants was reduced. The malformed veins were visible
      before the development of asymmetry of the leaf lamina and were maintained in
      mature as2 leaves. In vitro culture on phytohormone-free medium of leaf sections
      from as2 mutants and from the asymmetric leaves1 (as1) mutant, which has a
      phenotype similar to that of as2, revealed an elevated potential in both cases
      for regeneration of shoots from leaf cells. Analysis by the reverse transcription
      polymerase chain reaction showed that transcripts of the KNAT1, KNAT2 and KNAT6
      (a recently identified member of the class 1 knox family) genes accumulated in
      the leaves of both as2 and as1 plants but not of wild type. Transcripts of the
      STM gene also accumulated in as1 leaves. These findings suggest that, in leaves,
      the AS2 and AS1 genes repress the expression of these homeobox genes, which are
      thought to maintain the indeterminate cell state in the shoot apical meristem.
      Taken together, our results suggest that AS2 and AS1 might be involved in
      establishment of a prominent midvein and of networks of other veins as well as in
      the formation of the symmetric leaf lamina, which might be related to repression
      of class 1 knox homeobox genes in leaves.

PMID- 11311159
TI  - Visualization and functional characterization of the developing murine cardiac
      conduction system.
AB  - The cardiac conduction system is a complex network of cells that together
      orchestrate the rhythmic and coordinated depolarization of the heart. The
      molecular mechanisms regulating the specification and patterning of cells that
      form this conductive network are largely unknown. Studies in avian models have
      suggested that components of the cardiac conduction system arise from progressive
      recruitment of cardiomyogenic progenitors, potentially influenced by inductive
      effects from the neighboring coronary vasculature. However, relatively little is
      known about the process of conduction system development in mammalian species,
      especially in the mouse, where even the histological identification of the
      conductive network remains problematic. We have identified a line of transgenic
      mice where lacZ reporter gene expression delineates the developing and mature
      murine cardiac conduction system, extending proximally from the sinoatrial node
      to the distal Purkinje fibers. Optical mapping of cardiac electrical activity
      using a voltage-sensitive dye confirms that cells identified by the lacZ reporter
      gene are indeed components of the specialized conduction system. Analysis of lacZ
      expression during sequential stages of cardiogenesis provides a detailed view of
      the maturation of the conductive network and demonstrates that patterning occurs
      surprisingly early in embryogenesis. Moreover, optical mapping studies of
      embryonic hearts demonstrate that a murine His-Purkinje system is functioning
      well before septation has completed. Thus, these studies describe a novel marker
      of the murine cardiac conduction system that identifies this specialized network
      of cells throughout cardiac development. Analysis of lacZ expression and optical
      mapping data highlight important differences between murine and avian conduction
      system development. Finally, this line of transgenic mice provides a novel tool
      for exploring the molecular circuitry controlling mammalian conduction system
      development and should be invaluable in studies of developmental mutants with
      potential structural or functional conduction system defects.

PMID- 11311160
TI  - REF-1, a protein with two bHLH domains, alters the pattern of cell fusion in C.
      elegans by regulating Hox protein activity.
AB  - Hox genes control the choice of cell fates along the anteroposterior (AP) body
      axis of many organisms. In C. elegans, two Hox genes, lin-39 and mab-5, control
      the cell fusion decision of the 12 ventrally located Pn.p cells. Specific Pn.p
      cells fuse with an epidermal syncytium, hyp7, in a sexually dimorphic pattern. In
      hermaphrodites, Pn.p cells in the mid-body region remain unfused whereas in
      males, Pn.p cells adopt an alternating pattern of syncytial and unfused fates.
      The complexity of these fusion patterns arises because the activities of these
      two Hox proteins are regulated in a sex-specific manner. MAB-5 activity is
      inhibited in hermaphrodite Pn.p cells and thus MAB-5 normally only affects the
      male Pn.p fusion pattern. Here we identify a gene, ref-1, that regulates the
      hermaphrodite Pn.p cell fusion pattern largely by regulating MAB-5 activity in
      these cells. Mutation of ref-1 also affects the fate of other epidermal cells in
      distinct AP body regions. ref-1 encodes a protein with two basic helix-loop-helix
      domains distantly related to those of the hairy/Enhancer of split family. ref-1,
      and another hairy homolog, lin-22, regulate similar cell fate decisions in
      different body regions along the C. elegans AP body axis.

PMID- 11311161
TI  - Groucho augments the repression of multiple Even skipped target genes in
      establishing parasegment boundaries.
AB  - Groucho acts as a co-repressor for several Drosophila DNA binding transcriptional
      repressors. Several of these proteins have been found to contain both Groucho
      dependent and -independent repression domains, but the extent to which this
      distinction has functional consequences for the regulation of different target
      genes is not known. The product of the pair-rule gene even skipped has previously
      been shown to contain a Groucho-independent repression activity. In the Even
      skipped protein, outside the Groucho-independent repression domain, we have
      identified a conserved C-terminal motif (LFKPY), similar to motifs that mediate
      Groucho interaction in Hairy, Runt and Huckebein. Even skipped interacts with
      Groucho in yeast and in vitro, and groucho and even skipped genetically interact
      in vivo. Even skipped with a mutated Groucho interaction motif, which abolished
      binding to Groucho, showed a significantly reduced ability to rescue the even
      skipped null phenotype when driven by the complete even skipped regulatory
      region. Replacing this motif with a heterologous Groucho interaction motif
      restored the rescuing function of Even skipped in segmentation. Further
      functional assays demonstrated that the Even skipped C terminus acts as a Groucho
      dependent repression domain in early Drosophila embryos. This novel repression
      domain was active on two target genes that are normally repressed by Even skipped
      at different concentrations, paired and sloppy paired. When the Groucho
      interaction motif is mutated, repression of each target gene is reduced to a
      similar extent, with some activity remaining. Thus, the ability of Even skipped
      to repress different target genes at different concentrations does not appear to
      involve differential recruitment or function of Groucho. The accumulation of
      multiple domains of similar function within a single protein may be a common
      evolutionary mechanism that fine-tunes the level of activity for different
      regulatory functions.

PMID- 11311163
TI  - Genetic dissection of nodal function in patterning the mouse embryo.
AB  - Loss-of-function analysis has shown that the transforming growth factor-like
      signaling molecule nodal is essential for mouse mesoderm development. However,
      definitive proof of nodal function in other developmental processes in the mouse
      embryo has been lacking because the null mutation blocks gastrulation. We
      describe the generation and analysis of a hypomorphic nodal allele. Mouse embryos
      heterozygous for the hypomorphic allele and a null allele undergo gastrulation
      but then display abnormalities that fall into three distinct mutant phenotypic
      classes, which may result from expression levels falling below critical
      thresholds in one or more domains of nodal expression. Our analysis of each of
      these classes provides conclusive evidence for nodal-mediated regulation of
      several developmental processes in the mouse embryo, beyond its role in mesoderm
      formation. We find that nodal signaling is required for correct positioning of
      the anteroposterior axis, normal anterior and midline patterning, and the left
      right asymmetric development of the heart, vasculature, lungs and stomach.

PMID- 11311162
TI  - Germline and developmental roles of the nuclear transport factor importin alpha3
      in C. elegans.
AB  - The importin alpha family of transport factors mediates the nuclear import of
      classical nuclear localization signal-containing proteins. In order to understand
      how multiple importin alpha proteins are regulated both in individual cells and
      in a whole organism, the three importin alpha (ima) genes of Caenorhabditis
      elegans have been identified and studied. All three IMAs are expressed in the
      germline; however, only IMA-3 is expressed in the soma. RNA interference (RNAi)
      experiments demonstrate that IMA-3 is required for the progression of meiotic
      prophase I during oocyte development. Loss of IMA-3 expression leads also to a
      disruption of the nuclear pore complex accompanied by the mis-localization of P
      granules. A range of defects occurring in ima-3(RNAi) F1 progeny further supports
      a role for IMA-3 during embryonic and larval development. The functional
      association of IMA-3 with distinct cellular events, its expression pattern and
      intracellular localization indicate that regulation of the nuclear transport
      machinery is involved in the control of developmental pathways.

PMID- 11311164
TI  - Drosophila puckered regulates Fos/Jun levels during follicle cell morphogenesis.
AB  - puckered (puc) encodes a VH1-like phosphatase that down-regulates Jun kinase
      (JNK) activity during dorsal closure of the Drosophila embryo. We report a role
      for puc in follicle cell morphogenesis during oogenesis. puc mRNA accumulates
      preferentially in the centripetally migrating follicle cells and cells of the
      elongating dorsal appendages. Proper levels of Puc activity in the follicle cells
      are critical for the production of a normal egg: either reduced or increased Puc
      activity result in incomplete nurse cell dumping and aberrant dorsal appendages.
      Phenotypes associated with puc mutant follicle cells include altered DE-cadherin
      expression in the follicle cells and a failure of nurse cell dumping to
      coordinate with dorsal appendage elongation, leading to the formation of cup
      shaped egg chambers. The JNK pathway target A251-lacZ showed cell-type-specific
      differences in its regulation by puc and by the small GTPase DRac1. puc mutant
      cells displayed region-specific ectopic expression of the A251-lacZ enhancer trap
      whereas overexpression of a transgene encoding Puc was sufficient to suppress
      lacZ expression in a cell autonomous fashion. Strikingly, decreased or increased
      puc function leads to a corresponding increase or decrease, respectively, of Fos
      and Jun protein levels. Taken together, these data indicate that puc modulates
      gene expression responses by antagonizing a Rho GTPase signal transduction
      pathway that stabilizes the AP-1 transcription factor. Consistent with this,
      overexpression of a dominant negative DRac1 resulted in lower levels of Fos/Jun.

PMID- 11311165
TI  - A BAC transgenic analysis of the Mrf4/Myf5 locus reveals interdigitated elements
      that control activation and maintenance of gene expression during muscle
      development.
AB  - The muscle-specific transcription factors Myf5 and Mrf4 are two of the four
      myogenic regulatory factors involved in the transcriptional cascade responsible
      for skeletal myogenesis in the vertebrate embryo. Myf5 is the first of these four
      genes to be expressed in the mouse. We have previously described discrete
      enhancers that drive Myf5 expression in epaxial and hypaxial somites, branchial
      arches and central nervous system, and argued that additional elements are
      required for proper expression (Summerbell, D., Ashby, P. R., Coutelle, O., Cox,
      D., Yee, S. P. and Rigby, P. W. J. (2000) Development 127, 3745-3757). We have
      now investigated the transcriptional regulation of both Myf5 and Mrf4 using
      bacterial artificial chromosome transgenesis. We show that a clone containing
      Myf5 and 140 kb of upstream sequences is sufficient to recapitulate the known
      expression patterns of both genes. Our results confirm and reinforce the
      conclusion of our earlier studies, that Myf5 expression is regulated differently
      in each of a considerable number of populations of muscle progenitors, and they
      begin to illuminate the evolutionary origins of this complex regulation. We
      further show that separate elements are involved in the activation and
      maintenance of expression in the various precursor populations, reflecting the
      diversity of the signals that control myogenesis. Mrf4 expression requires at
      least four elements, one of which may be shared with Myf5, providing a possible
      explanation for the linkage of these genes throughout vertebrate phylogeny.
      Further complexity is revealed by the demonstration that elements which control
      Mrf4 and Myf5 are embedded in an unrelated neighbouring gene.

PMID- 11311166
TI  - Activation and repression by the C-terminal domain of Dorsal.
AB  - In the Drosophila embryo, Dorsal, a maternally expressed Rel family transcription
      factor, regulates dorsoventral pattern formation by activating and repressing
      zygotically active fate-determining genes. Dorsal is distributed in a ventral-to
      dorsal nuclear concentration gradient in the embryo, the formation of which
      depends upon the spatially regulated inhibition of Dorsal nuclear uptake by
      Cactus. Using maternally expressed Gal4/Dorsal fusion proteins, we have explored
      the mechanism of activation and repression by Dorsal. We find that a fusion
      protein containing the Gal4 DNA-binding domain fused to full-length Dorsal is
      distributed in a nuclear concentration gradient that is similar to that of
      endogenous Dorsal, despite the presence of a constitutively active nuclear
      localization signal in the Gal4 domain. Whether this fusion protein activates or
      represses reporter genes depends upon the context of the Gal4-binding sites in
      the reporter. A Gal4/Dorsal fusion protein lacking the conserved Rel homology
      domain of Dorsal, but containing the non-conserved C-terminal domain also
      mediates both activation and repression, depending upon Gal4-binding site
      context. A region close to the C-terminal end of the C-terminal domain has
      homology to a repression motif in Engrailed - the eh1 motif. Deletion analysis
      indicates that this region mediates transcriptional repression and binding to
      Groucho, a co-repressor known to be required for Dorsal-mediated repression. As
      has previously been shown for repression by Dorsal, we find that activation by
      Dorsal, in particular by the C-terminal domain, is modulated by the maternal
      terminal pattern-forming system.

PMID- 11311167
TI  - Non-imprinted Igf2r expression decreases growth and rescues the Tme mutation in
      mice.
AB  - In the mouse the insulin-like growth factor receptor type 2 gene (Igf2r) is
      imprinted and maternally expressed. Igf2r encodes a trans-membrane receptor that
      transports mannose-6-phosphate tagged proteins and insulin-like growth factor 2
      to lysosomes. During development the receptor reduces the amount of insulin-like
      growth factors and thereby decreases embryonic growth. The dosage of the gene is
      tightly regulated by genomic imprinting, leaving only the maternal copy of the
      gene active. Although the function of Igf2r in development is well established,
      the function of imprinting the gene remains elusive. Gene targeting experiments
      in mouse have demonstrated that the majority of genes are not sensitive to gene
      dosage, and mice heterozygous for mutations generally lack phenotypic
      alterations. To investigate whether reduction of Igf2r gene dosage by genomic
      imprinting has functional consequences for development we generated a non
      imprinted allele (R2Delta). We restored biallelic expression to Igf2r by deleting
      a critical element for repression of the paternal allele (region 2) in mouse
      embryonic stem cells. Maternal inheritance of the R2Delta allele has no
      phenotype; however, paternal inheritance results in biallelic expression of
      Igf2r, which causes a 20% reduction in weight late in embryonic development that
      persists into adulthood. Paternal inheritance of the R2Delta allele rescues the
      lethality of a maternally inherited Igf2r null allele and a maternally inherited
      Tme (T-associated maternal effect) mutation. These data show that the biological
      function of imprinting Igf2r is to increase birth weight and they also establish
      Igf2r as the Tme gene.

PMID- 11311168
TI  - Centrosome migration into the Drosophila oocyte is independent of BicD and egl,
      and of the organisation of the microtubule cytoskeleton.
AB  - During early Drosophila oogenesis, one cell from a cyst of 16 germ cells is
      selected to become the oocyte, and accumulates oocyte-specific proteins and the
      centrosomes from the other 15 cells. Here we show that the microtubule
      cytoskeleton and the centrosomes follow the same stepwise restriction to one cell
      as other oocyte markers. Surprisingly, the centrosomes still localise to one cell
      after colcemid treatment, and in BicD and egl mutants, which abolish the
      localisation of all other oocyte markers and the polarisation of the microtubule
      cytoskeleton. In contrast, the centrosomes fail to migrate in cysts mutant for
      Dynein heavy chain 64C, which disrupts the fusome. Thus, centrosome migration is
      independent of the organisation of the microtubule cytoskeleton, and seems to
      depend instead on the polarity of the fusome.

PMID- 11311169
TI  - even skipped is required to produce a trans-acting signal for larval neuroblast
      proliferation that can be mimicked by ecdysone.
AB  - Development of a multicellular organism requires precise coordination of cell
      division and cell type determination. The selector homeoprotein Even skipped
      (Eve) plays a very specific role in determining cell identity in the Drosophila
      embryo, both during segmentation and in neuronal development. However, studies of
      gene expression in eve mutant embryos suggest that eve regulates the embryonic
      expression of the vast majority of genes. We present here genetic interaction and
      phenotypic analysis showing that eve functions in the trol pathway to regulate
      the onset of neuroblast division in the larval CNS. Surprisingly, Eve is not
      detected in the regulated neuroblasts, and culture experiments reveal that Eve is
      required in the body, not the CNS. Furthermore, the effect of an eve mutation can
      be rescued both in vivo and in culture by the hormone ecdysone. These results
      suggest that eve is required to produce a trans-acting factor that stimulates
      cell division in the larval brain.

PMID- 11311170
TI  - Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes.
AB  - We present a detailed study of the genetic basis of mesodermal axial patterning
      by paralogous group 8 Hox genes in the mouse. The phenotype of Hoxd8 loss-of
      function mutants is presented, and compared with that of Hoxb8- and Hoxc8-null
      mice. Our analysis of single mutants reveals common features for the Hoxc8 and
      Hoxd8 genes in patterning lower thoracic and lumbar vertebrae. In the Hoxb8
      mutant, more anterior axial regions are affected. The three paralogous Hox genes
      are expressed up to similar rostral boundaries in the mesoderm, but at levels
      that strongly vary with the axial position. We find that the axial region
      affected in each of the single mutants mostly corresponds to the area with the
      highest level of gene expression. However, analysis of double and triple mutants
      reveals that lower expression of the other two paralogous genes also plays a
      patterning role when the mainly expressed gene is defective. We therefore
      conclude that paralogous group 8 Hox genes are involved in patterning quite an
      extensive anteroposterior (AP) axial region. Phenotypes of double and triple
      mutants reveal that Hoxb8, Hoxc8 and Hoxd8 have redundant functions at upper
      thoracic and sacral levels, including positioning of the hindlimbs.
      Interestingly, loss of functional Hoxb8 alleles partially rescues the phenotype
      of Hoxc8- and Hoxc8/Hoxd8-null mutants at lower thoracic and lumbar levels. This
      suggests that Hoxb8 affects patterning at these axial positions differently from
      the other paralogous gene products. We conclude that paralogous Hox genes can
      have a unique role in patterning specific axial regions in addition to their
      redundant function at other AP levels.

PMID- 11311171
TI  - Preferences for treatment during a first psychotic episode.
AB  - Psychiatric services providing care for patients and their families confronted
      with a first psychotic episode need to be sensitive towards patients' and
      families' preferences. Ten patients, ten family members and ten professional
      caregivers composed a list of 42 preferences in the treatment for a first
      psychotic episode. In total 99 patients, 100 family members and 263 professional
      caregivers evaluated these preferences, thus producing an order of priorities.
      There appears to be considerable agreement among the groups of respondents
      regarding their top ten priorities, especially concerning information on
      diagnosis and medication. However, we found important differences between groups
      of respondents. The results suggest that in psychiatric services great attention
      should be given to psycho-education and early outpatient intervention.

PMID- 11311172
TI  - Relapse prevention in schizophrenia: attitudes of neurologists-psychiatrists.
AB  - The overall high relapse rates observed in schizophrenia are attributed to
      several causes. One important factor influencing satisfactory prevention of
      relapse is the lack of consistent treatment strategies among medical doctors,
      especially neurologists-psychiatrists. Nearly one-third of the members of the
      Hellenic Society of Neurology and Psychiatry were asked to fill in anonymously a
      structured questionnaire on their treatment attitudes and prescribing tactics
      regarding schizophrenic patients both after the first schizophrenic episode and
      after multiple episodes. The majority of Greek neurologists-psychiatrists seem to
      adopt prescribing habits that approximate the current international standards for
      prevention of schizophrenic relapse. Their attitudes regarding the treatment and
      prevention of relapse for the first schizophrenic episode and first relapse are
      determined from multiple factors. These are: the expected relapse rates after the
      first episode, the expected prevalence of extrapyramidal side effects following a
      long-term neuroleptic treatment, the patient's expected treatment compliance
      after the first episode, the doctor's experience with treating schizophrenics,
      and lastly the knowledge of current literature on the topic. These results point
      to the need for continuing education, especially of the younger mental health
      professionals and those working in the private sector, addressing the issue of
      the actual risk of developing side effects from the treatment. In due course,
      benefits could result for everyday psychiatric practice and the patients'
      compliance with treatment.

PMID- 11311173
TI  - Responsiveness of subjective quality of life assessment in schizophrenic
      patients: a quasi-experimental pilot study.
AB  - Responsiveness of quality of life (QOL) assessments in chronic schizophrenic
      patients was investigated by a quasi-experimental pilot study. Satisfaction
      ratings were assessed over five time points with an externally imposed disturbing
      stimulus at the second time point. Despite a markedly high stability, the
      disturbance provoked a temporally limited decrease in QOL.

PMID- 11311174
TI  - Citalopram in mentally retarded patients with depression: a long-term clinical
      investigation.
AB  - The effect of citalopram was investigated in 20 mentally retarded patients
      suffering from a depressive disorder characterized by alterations in the domains
      of affectivity, motivation, motor activity and vital signs. The study followed a
      baseline-controlled open design. Citalopram was started in a daily dosage of 20
      mg that was kept unchanged for 6 weeks. Thereafter dosage was adjusted to
      maximally 60 mg per day. Treatment effects were assessed according to the
      Clinical Global Improvement Scale (CGIS) after at least 6 months. In 12 of the 20
      patients a moderate to marked improvement in all domains was observed upon
      treatment with 20-40 mg citalopram daily. Treatment for one year in the effective
      dose prevented recurrence of depressive symptomatology. Concomitant use of
      sedative anticonvulsants reduced responsiveness to treatment. No interactions
      were observed. It is concluded that citalopram is a well-tolerated, safe and
      effective antidepressant in mentally retarded subjects with depressive disorders.

PMID- 11311175
TI  - Subtyping of panic disorder patients with bradycardia.
AB  - PURPOSE: Since clinical practice suggests that panic disorder may not be a
      homogeneous condition, a study was carried out to test the possible existence of
      different groups or subgroups of panic patients. SUBJECTS AND METHODS: Thirty-two
      panic patients (DSM-III-R) underwent lactate challenge in our laboratory and were
      assessed for heart rate, blood pressure, sweating and Acute Panic Inventory.
      RESULTS: During the lactate challenge, patients complaining mainly of
      'cardiorespiratory' symptoms (N = 12) showed tachycardia and localized sweating.
      Conversely, patients complaining mainly of 'pseudoneurological' symptoms (N = 16)
      showed bradycardia and generalized sweating. In both groups, Acute Panic
      Inventory scores were significantly higher during than before the panic attack,
      but the distribution of the scores was markedly different. DISCUSSION AND
      CONCLUSION: The results suggest that panic disorder may be a heterogeneous
      condition. Implications of these results to other phobic disorders, to Klein's
      false suffocation alarm theory and to the 'extended amygdala model' are
      discussed.

PMID- 11311176
TI  - Clinical features and co-morbidity of social phobics in Turkey.
AB  - The aim of this study is to investigate the clinical features and frequency and
      importance of related co-morbid disorders of social phobia in a clinical sample.
      Eighty-seven patients meeting DSM-III-R diagnostic criteria for social phobia
      were studied. All patients were assessed by using a semi-structured socio
      demographic form, the Structured Clinical Interview for DSM-III-R, Manual for the
      Structured Clinical Interview for DSM-III-R Personality Disorders, Liebowitz
      Social Anxiety Scale, Hamilton Rating Scale for Depression and Hamilton Rating
      Scale for Anxiety. Sixty-eight (78.2%) of the group were male, 19 (21.8%) were
      female. The ages varied between 16-58 years, with a mean of 26.2 years (SD =
      8.5). Fifty-one point seven percent of the subjects were assessed as having a co
      morbid axis I disorder, of which 12.6% consisted of panic disorder and 10.3%
      agoraphobia. An additional axis II disorder had been found in 67.8% of the
      subjects, and 54.0% of them had been diagnosed as having avoidant personality
      disorder. The frequency of co-morbid disorders in our social phobic sample is
      lower than most of the studies in the literature. The interface between social
      phobia and avoidant personality disorder needs to be studied and discussed
      further.

PMID- 11311177
TI  - A comparison of the validity of two psychiatric screening questionnaires: the
      Arabic General Health Questionnaire (AGHQ) and Self-Reporting Questionnaire (SRQ
      20) in UAE, using Receiver Operating Characteristic (ROC) analysis.
AB  - This study compared the ability of the Arabic General Health questionnaire (AGHQ)
      and Self-Reporting Questionnaire (SRQ-20) to screen ICD-10 psychiatric disorders
      in an Arab community in Al Ain, United Arab Emirates. Standardised psychiatric
      assessments of subjects using the Composite International Diagnostic Interview
      (CIDI) were carried out. The Receiver Operating Characteristic (ROC) analysis was
      used to determine validity indices for the AGHQ and SRQ-20. For the AGHQ,
      sensitivity, specificity and area under the curve (AUC) were 86, 85 and 93%
      respectively, while for the SRQ-20, validity indices were 83, 83 and 90%
      respectively. Overall performance of the AGHQ was significantly better than the
      SRQ-20, especially in males and those under the age of 30 years. We conclude that
      both questionnaires are valid screening instruments in an Arab community in the
      UAE.

PMID- 11311178
TI  - Subjective effects of MDMA ('Ecstasy') on human sexual function.
AB  - Sexual function following 3,4-Methylenedioxymethamphetamine (MDMA, or 'Ecstasy')
      consumption was subjectively evaluated in 35 healthy recreational users (20 men
      and 15 women, aged 21-48 years) with regard to four major domains of sexual
      activity: desire, erection (lubrication in women), orgasm and satisfaction.
      Desire and satisfaction were moderately to profoundly increased by MDMA in more
      than 90% of subjects. Orgasm was delayed but perceived as more intense. Erection
      was impaired in 40% of the men. It seems that MDMA impairs sexual performance, in
      spite of enhancement of sexual desire and the perception of greater satisfaction.

PMID- 11311179
TI  - Survey of patient satisfaction in adult psychiatric outpatient clinics.
AB  - A client satisfaction survey was undertaken in two adult psychiatric outpatient
      clinics. The anonymous self-report questionnaire covering demographic, setting
      and satisfaction with service variables was endorsed by 203 participants. The
      mean age of the subjects was 42.5 +/- 19 years, with a small majority (58.6%) of
      females. Overall satisfaction with psychiatric care was high (79.8%). None of the
      demographic or setting variables correlated significantly with satisfaction.
      Psychoeducation was significantly correlated with level of satisfaction with
      services. These findings further emphasize the importance of psychoeducation by
      service providers in mental health.

PMID- 11311180
TI  - Risperidone-induced ejaculatory dysfunction: a case report.

PMID- 11311181
TI  - An interferon-alpha-induced psychotic disorder in a patient with chronic
      hepatitis C.

PMID- 11311182
TI  - Violent suicide attempts: socio-demographics, clinical profile, cultural
      repeaters?

PMID- 11311183
TI  - Critical issues in the economic evaluation of interventions against communicable
      diseases.
AB  - Economic appraisal seeks to provide policy-makers with guidance about how scarce
      resources can be used to derive the greatest possible social benefit. Its use in
      the health sector has increased dramatically over the last decade although much
      of it has been focused on the problems of the more developed countries. The
      relatively sparse literature on communicable diseases has been dominated by
      interventions related to HIV/AIDS, hepatitis, malaria and tropical diseases.
      Reviews of this literature from the perspective of specific conditions such as
      Hepatitis B are already available, and recently the entire literature has been
      evaluated against the technical criteria for economic evaluations published in
      standard textbooks. Accordingly, this paper focuses on issues which would make
      economic appraisal more useful to policy-makers than it currently is. Given that
      few countries have the resources to undertake all the necessary analysis in their
      own settings, it is important that studies in one setting are undertaken in a way
      that allow generalisability to similar settings. Some of the most important
      challenges this poses for cost-effectiveness analysis (CEA) are identified.
      Firstly, incremental analysis is appropriate to local decision making when policy
      makers are constrained to keep the current interventions and can consider only
      marginal improvements. However, it does not allow re-evaluation of existing
      interventions and is not transferable across settings. A version of Generalised
      CEA is proposed as an alternative. Secondly, data on costs and effectiveness are
      often not presented appropriately. The challenge for effectiveness is to adjust
      the evidence from efficacy studies to allow for different patient or population
      groups, and local variations in adherence, coverage, and infrastructure. For
      costs, it is important for studies to report the physical resources used in an
      intervention as well as unit prices. Thirdly, some long-term effects are still
      not well incorporated into CEA, especially those affecting child development and
      drug resistance. These questions are technically challenging and require more
      concerted efforts over the next few years. Finally, it is important for analysts
      to provide decision-makers with estimates of the resources that would be required
      to implement interventions claimed to be cost-effective. These improvements would
      better enable the evidence from economic analyses to enter the policy debate and
      be weighed against the other goals and objectives of the health system when
      allocating scarce resources.

PMID- 11311184
TI  - Bionomics of Anopheles sacharovi in Ardebil province, northwestern Iran during a
      larval control program.
AB  - Studies were conducted on the ecology of Anopheles sacharovi over a period of 12
      months in Parsabad and Germi counties, Ardebil province, Iran. The species was
      active from June to late November with one peak of activity in early August on
      the plain of Parsabad, and from late June to late November with one peak of
      activity in late August in mountainous areas of Germi. Chemical analysis of the
      water in larval habitats showed that the water contained calcium bicarbonate and
      sodium sulphate, and the limit of salinity was 263--414 mg/l. Dissection of A.
      sacharovi from three villages during July in Parsabad indicated a very low parity
      rates all were found negative for sporozoites. ELISA testing of 210 blood meals
      of the species, showed that few of those found in cowsheds or chicken coops had
      fed on humans, but of those found in bedrooms 38.5% had fed on humans.
      Insecticide susceptibility tests showed that the species is susceptible to
      malathion and propoxur but resistant to DDT and dieldrin.

PMID- 11311185
TI  - Dog ecology and demography information to support the planning of rabies control
      in Machakos District, Kenya.
AB  - A study of 150 dog-owning households from six randomly selected sublocations was
      conducted in Machakos District, Kenya. Initially, all households were visited to
      collect information on dog ecology and demography based on WHO guidelines and to
      collect serum for rabies antibody detection. A second visit was made 1 year
      later, to obtain follow-up data on births, deaths, dog movements and other events
      since the first visit. Dog ownership was common, with a range of 53--81%
      (mean=63%) of households owning dogs in the six sublocations. Dog density for the
      five more rural sublocations ranged from 6 to 21 dogs km(-2) and for the peri
      urban sublocation was 110 dogs km(-2). The dog population was estimated to be
      growing at 9% p.a. (95% C.I. 4--14%). This growth was a function of very high
      fecundity (1.3 females per female per year) more than compensating for high
      mortality, particularly among females. Life expectancy from birth was 3.5 years
      for males and 2.4 years for females. Half the dogs at any one time were less than
      1 year of age. All dogs, by design of the study, were owned. Of these, 69% were
      never restricted and roamed freely to forage for food and mix with other dogs.
      Only a small proportion of dogs (5%) were fed commercial dog food. Most
      households reported observing dogs scavenging their garbage, including: their own
      dogs (81%), their neighbours' dogs (75%) and unknown dogs (45%). Only 29% of dogs
      at least 3 months of age were reported to be vaccinated against rabies. The
      proportion vaccinated varied widely between sublocations (5--68%); 48% of dogs
      reportedly vaccinated had detectable antibodies, 31% at or above levels
      considered to indicate seroconversion. The proportion of dogs with detectable
      antibodies declined according to the time since last vaccination (55% if
      vaccinated < or = 1 year, 47% < or = 2 years and 36% > 2 years); 20% of dogs
      reported not to have been vaccinated had detectable rabies antibody. Compared to
      other dog populations in rural eastern and southern Africa, Machakos District has
      a high density of dogs. The Machakos dog population is growing, highly dynamic,
      poorly supervised and inadequately vaccinated against rabies. The main
      implication for rabies control is that adequate vaccination coverage is unlikely
      to be achieved, even under optimal delivery, using the current strategy of annual
      vaccination of dogs older than 3 months.

PMID- 11311186
TI  - Molecular analysis of DHFR and DHPS genes in P. falciparum clinical isolates from
      the Haut--Ogooue region in Gabon.
AB  - The main objective of this work was to determine the prevalence of mutations in
      genes coding for the dihydropteroate synthase (DHPS) and the dihydrofolate
      reductase (DHFR) enzymes which are implicated in resistance of P. falciparum to
      antifolate (pyrimethamine-sulfadoxine (P/S)). In this study, 117 human blood
      samples were collected at Franceville located in the region of Haut-Ogooue (South
      eastern Gabon). In this area, a relatively low level of sensitivity of Plasmodium
      falciparum to P/S has been reported with 18.2% of RII and 12.1% of RI resistance.
      A nested polymerase chain reaction was used to amplify a fragment of the DHFR
      gene containing codon 108, where a point mutation causing a Serine (wild type) to
      Asparagine or to a Threonine (resistant types) change occurs in pyrimethamine
      resistant parasites. Eleven DHFR fragments were sequenced and mutations occurring
      at codons 51, 59 and 108 were analysed. The DHPS gene was amplified by polymerase
      chain reaction (PCR) and sequenced directly or after cloning. Variant amino acid
      residues 436, 437, 540, 581, 613 associated with sulfadoxine resistance were
      analysed. The analysis of codon 108 of the DHFR gene was undertaken for 81
      isolates. More than one DHFR P. falciparum genotype was present in 64% of the
      samples. We showed that 47% of 141 DHFR gene PCR products had Serine (wild
      phenotype), and 52% had Asparagine. We found one isolate with the Thr-108
      confirmed by sequencing of the PCR product. Triple, double and single DHFR mutant
      at positions 51, 59 and 108 were found. Only codons 436 and 437 of the 38
      analysed sequences of the DHPS gene revealed point mutations. These results have
      been compared with those reported from different sites in Africa, Asia or South
      America.

PMID- 11311187
TI  - A preliminary study of the population genetics of Aedes aegypti (Diptera:
      Culicidae) from Mexico using microsatellite and AFLP markers.
AB  - Dengue fever recently reemerged in the Americas. Because vaccines are still under
      development, dengue prevention depends entirely on vector control. Since Aedes
      aegypti (Linnaeus, 1762) is the principal vector of this arbovirus, knowledge of
      the genetic structure of the insect is therefore required to maintain effective
      vector control strategies and to estimate levels of gene flow from which movement
      can be inferred. This preliminary study uses microsatellite and amplified
      fragment length polymorphism (AFLP) markers, to provide insights into genetic
      diversity of A. aegypti populations from different districts of two towns,
      located in the north-west of Mexico, Hermosillo and Guaymas. Although the
      microsatellites used were found to display limited polymorphism, they allowed
      discrimination between mosquitoes from the northern and the southern districts of
      Hermosillo. Using AFLP markers, clustering of individuals from the same town and
      from the same district was observed. Data from microsatellite and AFLP markers
      analysis both suggest that reinvasion of A. aegypti probably occurs from Guaymas
      to Hermosillo.

PMID- 11311188
TI  - Comparison of self-reported and observed water contact in an S. mansoni endemic
      village in Brazil.
AB  - Estimates of exposure are critical for immuno-epidemiologic and intervention
      studies in human schistosomiasis. Direct observation of human water contact
      patterns is both costly and time consuming. To address these issues, we
      determined whether individuals residing in a Schistosoma mansoni endemic village
      in Brazil could accurately self-report their water contact patterns. We compared
      the results of a water contact questionnaire to the present gold standard, direct
      observation of water contact in 86 volunteers, aged 8--29. We administered a
      survey to estimate volunteers' frequency and type of water contact and directly
      measured each volunteers' water contact patterns during 5 weeks of detailed water
      contact observations. We found a poor correlation between self reported frequency
      of contact and directly observed exposure (rho=0.119, P=NS). The questionnaire
      data was supplemented by information about average body surface area of exposure
      and duration of contact for specific activities derived from observations of this
      cohort. This 'supplemented questionnaire' data was significantly correlated with
      their exposure index (rho=0.227, P=0.05). It provides a starting point from which
      questionnaires may develop to provide a more cost-effective and less labor
      intensive method of assessing water contact exposure at the level of the
      individual.

PMID- 11311189
TI  - Use of DNA-based diagnostic methods for human leishmaniasis in Minas Gerais,
      Brazil.
AB  - DNA hybridisation was used to type 26 samples from lesions of human patients from
      the Rio Doce Valley (Minas Gerais, Brazil) clinically diagnosed as having
      cutaneous leishmaniasis, using kinetoplast DNA (kDNA) cloned mini-circle probes
      specific for the Leishmania mexicana and Leishmania braziliensis complexes. All
      samples were found to belong to the L. braziliensis complex. When biopsies were
      pressed directly onto touch blot membranes 38.5% of the samples were positive.
      The positivity and specificity obtained were both 100% when cultured blotted
      parasites were used. The results were confirmed by polymerase chain reaction
      (PCR) analysis using primers specific for the L. mexicana and L. braziliensis
      complexes.

PMID- 11311190
TI  - Reaching National Cholesterol Education Program Goals: a managed care approach to
      improving hyperlipidemia disease management outcomes. Introduction.

PMID- 11311191
TI  - Clinical context: current concepts of coronary heart disease management.
AB  - Coronary heart disease (CHD) is the single greatest cause of death among adults
      in the United States. It is also a major cause of disability and is associated
      with direct and indirect costs that exceed $118 billion annually. Elevation of
      serum lipid levels, particularly low-density lipoprotein cholesterol (LDL-C)
      levels, is closely linked to the development of CHD. Lipid levels that increase
      the risk of CHD are present in nearly one third of the US population. Large-scale
      intervention studies have shown that decreasing LDL-C can significantly reduce
      the risk of cardiovascular mortality, adverse cardiovascular events, and the
      requirement for revascularization procedures. Statins are now thought the most
      effective agents for lowering LDL-C, and they also have positive effects on other
      components of the serum lipid profile. These drugs are also better tolerated than
      other lipid-lowering agents. Statin therapy significantly decreases the risk of
      cardiovascular disease and is a cost-effective cardiovascular treatment according
      to current standards. Because statins vary substantially in acquisition cost,
      using statins in the most cost-effective manner is important for controlling
      health-care costs. Optimizing the cost-effectiveness of statin therapy is a
      particular concern to managed care organizations in light of the large number of
      patients who are now considered candidates for this treatment.

PMID- 11311192
TI  - A means to an end: an overview of a hyperlipidemia outcomes management program.
AB  - Quality management and improvement are increasingly important to managed care
      organizations (MCOs) as competition increases. One key area on which quality
      improvement programs can focus is MCO activity in helping patients remain
      healthy. Screening for and treatment of hyperlipidemia are important components
      of the preventive care of patients who are at risk for coronary heart disease
      (CHD). This article summarizes the methodology of a three-phase hyperlipidemia
      outcomes management program being implemented by 27 US health plans. Phase 1
      identifies inefficiencies in the clinical management of hyperlipidemia by
      assessing patients' attainment rates of low-density lipoprotein cholesterol (LDL
      C) targets. This information is then used to develop a multifactorial
      intervention program for CHD prevention in phase 2. The interventions for
      physicians include provision of treatment algorithms for patients with varying
      degrees of hyperlipidemia, education programs encouraging appropriate treatment
      of hyperlipidemia, and academic detailing summarizing phase 1 results and
      providing applicable literature. In phase 3, patient records are reassessed at
      least 6 months after the educational intervention. This three-phase program has
      the potential to improve patient care, reduce unnecessary treatment costs,
      provide a means of quality improvement, and increase plan value to potential
      purchasers.

PMID- 11311193
TI  - Assessing the results: phase 1 hyperlipidemia outcomes in 27 health plans.
AB  - In phase 1 of this hyperlipidemia outcomes management program, characteristics of
      7,619 patients treated with statins at 27 US managed care plans were determined.
      Nearly 40% (3,018 patients) had documented coronary heart disease (CHD). Most
      (65%) had at least two CHD risk factors. Hyperlipidemia treatment included
      simvastatin (39%), atorvastatin (25%), fluvastatin (14%), pravastatin (12%), and
      lovastatin (2%). On-treatment low-density lipoprotein cholesterol (LDL-C) levels
      were available for 79% of patients; however, only 46% had both baseline and
      follow-up levels recorded in their charts. Of patients for whom follow-up data
      were available, 3,779 (63%) achieved their target LDL-C levels as recommended by
      the National Cholesterol Education Program (NCEP). Target LDL-C levels were
      reached by 1,381 (87%) of the patients with a goal of 160 mg/dL, 1,326 (65%) of
      those with a goal of 130 mg/dL, and 1,072 (44%) of those with a goal of 100
      mg/dL. Overall, 66% of patients who met their treatment goal and 24% of those who
      did not required no more than a 25% reduction in LDL-C. In contrast, 8% of
      patients who achieved goals and 36% of patients who did not required >40%
      reduction in LDL-C. Phase 1 results did not suggest any substantial difference
      among statins for achievement of NCEP goals or decrease in LDL-C. These results
      show that therapy with statins is effective for achievement of NCEP targets in
      most patients and that there is potential for improvement in the quality and cost
      effectiveness of statin therapy with carefully planned interventions.

PMID- 11311194
TI  - Lipid-lowering interventions in managed care settings.
AB  - Effective screening, treatment, and follow-up of patients with elevated serum
      lipid levels is important because of the very strong association between this
      condition and coronary heart disease (CHD). Screening of patients with and
      without CHD for hyperlipidemia is not generally carried out properly by managed
      care organizations (MCOs) or in other settings. Primary and secondary prevention
      are inadequate in most patients with this condition; even in patients who are
      treated, lipid-lowering therapy is often not used to its full potential. These
      trends have been confirmed by findings in the first of a three-phase
      hyperlipidemia outcomes management program carried out at 27 US MCOs. The
      efficacy of lipid-lowering therapy can be enhanced by physician education and
      comprehensive, integrated quality improvement programs. The cost-effectiveness of
      such treatment can be improved by individualizing both drug and dose to achieve
      National Cholesterol Education Program goals at the lowest drug acquisition cost.
      The quality improvement program described and others like it have the potential
      to reduce the morbidity and mortality associated with CHD while decreasing the
      huge economic burden associated with this disease. Several such programs have
      been undertaken at MCOs, some with more success than others. Interventions and
      assessments of the type planned in phases 2 and 3 of this program can help to
      reduce the cost of lipid-lowering therapy without compromising cholesterol goal
      achievement.

PMID- 11311195
TI  - A comparison of human dental plaque microcosm biofilms grown in an undefined
      medium and a chemically defined artificial saliva.
AB  - The growth and pathogenic properties of dental plaque result from interactions
      between the microbiota and the oral environment and have been studied in
      laboratory experimental systems ranging from single or a few species (such as in
      chemostats) to dental plaque microcosms. Microcosm plaque is an in vitro version
      of natural plaque and has been explored as a microflora model because it is sited
      a more manipulable and controllable environment. It is obtained as microcosm
      biofilms in an 'artificial mouth' plaque culture system by culturing the bacteria
      in natural plaque-enriched saliva (i.e. salivary bacteria where a whole-saliva
      donor has abstained from oral hygiene for 24 h to increase the plaque bacteria in
      the saliva). The aim here was to examine whether a new, chemically defined
      analogue of saliva (defined medium mucin, DMM) could substitute for a previously
      used, chemically undefined medium (basal medium mucin, BMM) as an analogue of
      saliva for large-scale biofilm culturing. DMM contains various ions, mucin, amino
      acids, vitamins and growth factors at concentrations generally similar to those
      in saliva, whereas BMM contains yeast extract, peptones and mucin. To model the
      nutrient functions of salivary proteins, amino acids equivalent to 5 g/l casein
      were also included in DMM. In earlier studies, BMM-grown plaques were similar to
      natural plaques in structure, composition, growth rate and pH response to
      substrates. Their doubling-time patterns over a 20-day period were similar,
      except that the DMM-grown plaques showed biphasic growth patterns that were more
      pronounced than with BMM. Variation in enzyme profiles between BMM- and DMM-grown
      plaque, measured using the API-ZYM technique, provided evidence of nutritional
      effects on plaque composition. It was concluded that realistic growth rates and
      patterns are generated in microcosm plaque biofilms by supplying both DMM and
      BMM. However, the use of DMM enables specific modifications to be made to
      nutrient conditions during large-scale culture in our 'artificial mouth' biofilm
      system.

PMID- 11311196
TI  - The effect of low-dose interleukin-2-based immunotherapy on salivary function and
      composition in patients with metastatic renal cell carcinoma.
AB  - One of the side-effects accompanying low-dose recombinant interleukin-2 (rIL-2)
      based immunotherapy is salivary hypofunction. We evaluated the functional and
      compositional whole salivary profile at both resting and stimulated conditions in
      10 renal cell carcinoma patients who received prolonged low-dose rIL-2-based
      immunotherapy. Following the termination of 4 weeks of the combined
      administration of rIL-2 and recombinant interferon-alpha (rIFN-alpha), we found
      significant reductions of salivary flow rates at resting condition, accompanied
      by significant multiple compositional alterations, including increases in
      calcium, magnesium and phosphate concentrations, and significant reductions in
      total protein concentration. In contrast, no flow rate reduction was noted under
      stimulated condition, and the only significant altered compositional component
      was the phosphate. We recommend salivary-supporting therapies and anticariogenic
      treatments for patients undergoing low-dose rIL-2-based immunotherapy.

PMID- 11311197
TI  - The role of cyclic AMP response element-binding protein in testosterone-induced
      differentiation of granular convoluted tubule cells in the rat submandibular
      gland.
AB  - The postnatal development of granular convoluted tubules (GCT) in the duct system
      of the rodent submandibular gland is known to be androgen-dependent, but the
      underlying molecular mechanism is unclear. To test the possible role of the
      transcription factor, cyclic AMP response element-binding protein (CREB), in the
      androgen-induced differentiation of GCT, the effect of testosterone on the
      expression and localization of epidermal growth factor (EGF), a marker of GCT
      cells, and of CREB was examined in the submandibular glands of immature 3-week
      old rats. Northern blotting demonstrated increases in both EGF and CREB mRNA 1-4
      days after testosterone administration. Immunoprecipitation also indicated that
      CREB protein was increased in amount with testosterone administration, and that
      induced CREB was phosphorylated at the serine residue as in the active form of
      CREB. In situ hybridization demonstrated that cells with CREB mRNA signal first
      appeared in the distal portions of striated ducts at 1 day and had increased in
      number by 4 days after giving testosterone, when cells with EGF mRNA signal
      became evident in the same duct portions. Immunohistochemistry also showed the
      occurrence of CREB protein in the nuclei of duct epithelial cells before their
      differentiation into EGF-positive GCT cells. Finally, pieces of submandibular
      gland from immature rats were cultured in vitro and their expression of EGF mRNA
      analysed by the reverse transcriptase-polymerase chain reaction. Testosterone in
      the medium caused a marked enhancement of EGF expression in the gland in 1-4
      days, which was attenuated by simultaneous administration of the antisense
      oligonucleotide for CREB as well as that for the androgen receptor. These results
      suggest the CREB is upregulated by androgen and has a crucial role in androgen
      induced differentiation of GCT in the duct system of the rat submandibular gland.

PMID- 11311198
TI  - Localization and density of myeloid leucocytes in the periodontal ligament of
      normal rat molars.
AB  - The phenotypic distribution and density of macrophage-associated antigen
      expressing cells in the periodontal ligament (PDL) of normal rat mandibular first
      molars was evaluated by immunohistochemistry, and an attempt made to identify
      dendritic cells (DCs) by immunoelectron microscopy. Cells immunopositive to ED1
      (a general macrophage marker) were widely distributed throughout the PDL and were
      most common around blood vessels. A small number of T lymphocytes and OX62 (anti
      veiled cells and gammadelta T cells)-positive DC-like cells were also found. The
      relative density of cells immunopositive to ED9 (CD14), OX42 (CD11b), OX6 (anti
      class II MHC molecules), ED2 (anti-tissue-resident macrophages), 8A2 (CD11c) and
      WT.1 (CD11a) varied in the mesial, distal and periapical regions of the distal
      root and the furcal region. This finding suggests that there are several
      subpopulations of ED1-positive cells which express various combinations of these
      markers. Immunoelectron microscopy revealed that a small, but distinct,
      subpopulation of ED1- and OX6-positive cells did have a DC-like ultrastructure,
      although the majority of these cells were identified as macrophages. The DC-like
      cells were characterized by poorly developed lysosomal structures and an absence
      of phagocytic vesicles. It was concluded that the normal rat PDL is equipped with
      heterogeneous populations of macrophages with regional variations in density. The
      DC-like cells may function as antigen-presenting cells.

PMID- 11311199
TI  - P-glycoprotein expression in human major and minor salivary glands.
AB  - Sodium pump and carbonic anhydrase activity have been described in the salivary
      glands. However, it remains to be elucidated whether these energy sources are
      used for secretion, excretion or both. In addition, the differences in the
      function of excretion and the role of the excretory duct cells are currently
      unknown in salivary glands. Expression of P-glycoprotein (P-gp), which is an
      ATPase-binding efflux pump, was tested in normal major and minor salivary glands
      from humans. P-gp was distributed on the basolateral membrane of serous acinar
      cells in the major salivary glands and the minor salivary glands. In particular,
      it was found to be present on the basolateral membrane and cytoplasm of acinar
      demilunar cells in the anterior lingual gland. Intense expression was identified
      in the basolateral membrane of the striated duct cells of the major salivary
      glands. P-gp was distinctly positive in the basolateral and/or luminal membranes
      of the initial part and in the luminal membrane of the terminal part of the
      excretory duct cells of the major salivary glands, whereas it was positive in the
      luminal membranes of both the initial part and the terminal part of the excretory
      duct cells of the minor salivary glands. These disparate distributions between
      the major and the minor salivary glands suggest different physiological
      excretions in the striated duct. P-gp may be physiologically involved in an
      important part of the transporter system, not only in the acinar serous cells and
      the striated duct cells, but also in the excretory duct cells in the salivary
      glands.

PMID- 11311200
TI  - Distribution of MUC1 in the normal human oral cavity is localized to the ducts of
      minor salivary glands.
AB  - The change in expression of MUC1 from health to disease forms the basis of its
      use as a potential disease marker. Previous attempts at isolating MUC1 from
      normal, healthy human oral mucosa have, however, drawn conflicting conclusions as
      to its presence. Furthermore, when MUC1 was detected in the oral glycocalyx, it
      was not clear which cells were synthesising it. We examined human oral glycocalyx
      using pooled buccal smears from 50 normal individuals. Following isopycnic
      density centrifugation and membrane extraction with octyl glucoside and saponin,
      MUC1 was detected with the polyclonal antibody CT1. Immunohistochemistry using
      antibodies CT1 and BC2 was performed on sections from eight labial, seven
      palatal, four buccal, three retromolar pad, three dorsum of tongue and two
      ventral surface of tongue biopsies. In-situ hybridisation using MUC1 and
      cytoplasmic tail oligoprobes on sections from four palatal, seven labial and two
      retromolar pad biopsies was also carried out. MUC1 mRNA could only be detected in
      the minor salivary mucous glands. MUC1 has already been identified in the ducts
      of normal parotid and submandibular gland, and our findings demonstrate a similar
      distribution in minor salivary glands. We conclude that when present in the
      normal oral glycocalyx, the only oral source of MUC1 is from cell membranes of
      the minor salivary glands.

PMID- 11311201
TI  - Interleukin-1beta in antigen-induced arthritis of the rabbit temporomandibular
      joint.
AB  - The aim was to investigate joint perfusate levels of interleukin-1beta (IL-1beta)
      in antigen-induced monoarthritis of the rabbit temporomandibular (TMJ) and knee
      joints. Twenty-four adult male New Zealand White rabbits were divided into three
      groups: a control group as well as TMJ arthritis and knee joint arthritis groups.
      After sensitization, unilateral arthritis was induced by intra-articular
      injection with ovalbumin and the contralateral joint was injected with saline 3
      weeks after induction of arthritis. Joints were then perfused continuously with
      saline and samples were collected at 10-min intervals over a 50-min period. The
      IL-1beta concentrations in the samples were then analyzed. After killing the
      animals, the joints were examined histologically. The IL-1beta concentrations in
      the samples from the arthritic TMJs and knee joints were significantly higher
      than in the saline-injected and the control joints. Histological signs of chronic
      arthritis of similar severity were found in both joints. The IL-1beta levels in
      the samples from the arthritic TM and knee joints correlated with the
      histological severity of the arthritis, including pannus formation. In
      conclusion, this study shows that IL-1beta is released in the synovium of rabbit
      TMJs and knee joints during antigen-induced arthritis, and that high IL-1beta
      levels in synovial fluid are associated with histological signs of inflammation
      including, pannus tissue formation.

PMID- 11311202
TI  - Amplification of extracellular matrix and oncogenes in tat-transfected human
      salivary gland cell lines with expression of laminin, fibronectin, collagens I,
      III, IV, c-myc and p53.
AB  - Considerable progress has been made in the transfer of foreign genes into
      salivary glands in vivo using adenovirus vectors in rats. In an attempt to avoid
      the transient expression inherent, when using these vectors, retroviral vectors
      and human cell lines where used here in attempt to develop an in vitro model of
      HIV-associated salivary gland disease. The HIV-1-tat protein is increasingly
      implicated in the pathogenesis of the AIDS through altering the expression of
      strategic cellular genes. The purpose of this study was to transfect human
      salivary gland (HSG) cell lines in vitro, with the pHIV-1/LTR-tat plasmid, and
      examine the effect of tat on expression of matrix and basement membrane genes
      known to be important in the pathogenesis of salivary gland disease. HSG cells
      were transfected with HIV-1-tat plasmid by the lipofection method. Transfection
      was confirmed by polymerase chain reaction (PCR) and Southern blot, which
      verified that tat-specific DNA was present. Tat-mRNA was analysed by Northern
      blotting and quantified by reverse transcriptase polymerase chain reaction (RT
      PCR) to demonstrate its expression. Numerous clones were found to contain
      integrated tat DNA sequences and analysis of mRNA showed stable expression of tat
      specific RNA. Further analysis of mRNA expression for various marker proteins
      important in HIV pathogenesis showed that the HSG cell line transfected with HIV
      1-tat, was associated with significant induction of mRNA expression for
      extracellular matrix protein. Tat-amplified transcription of the major basement
      membrane protein laminin, as well as of fibronectin, collagen I and III, and c
      myc oncogene was demonstrated. Conversely, expression of p53 suppressor gene mRNA
      was reduced. Post-transfection expression of collagen IV was erratic and
      inconclusive. It was concluded that the presence of HIV-tat in this in vitro
      model of salivary ductal epithelial cell model alters the mRNA expression of
      several matrix, basement membrane and oncoproteins known to be involved in HIV
      pathogenesis. These cell lines provide a useful system for studying the role of
      tat in the immunopathogenesis of HIV-associated salivary gland disease.

PMID- 11311203
TI  - The immunohistochemical localization of Bax and Bcl-2 and their relation to
      apoptosis during amelogenesis in developing rat molars.
AB  - Bax and Bcl-2 are members of a family of intracellular, membrane-associated
      proteins that regulate programmed cell death. It has been suggested that, when
      Bax predominates, programmed cell death is accelerated and the apoptosis
      inhibitory activity of Bcl-2 is suppressed. The present study was undertaken to
      immunohistochemically (IHC) localize Bax and Bcl-2 in the cells of the enamel
      organ during amelogenesis in rat molars. Also, apoptotic cells were detected by
      TUNEL staining. The IHC intense localization of Bcl-2 and light staining for Bax
      in the pre-ameloblasts suggest that apoptosis is inhibited in the proliferating
      pre-ameloblasts. This is consistent with an absence of TUNEL staining for
      apoptosis in these cells. However, in the late secretory and transition
      ameloblasts, and adjacent stratum intermedium, evidence of apoptosis of the
      ameloblasts was observed. Bax and Bcl-2 were co-localized in the proximal ends of
      late secretory, transition and early maturation-stage ameloblasts, but
      immunoreactivity for Bax markedly increased in the proximal ends of late
      secretory and transition ameloblasts, while the Bcl-2 staining appeared to be
      lighter. This suggests that Bax antagonized Bcl-2 function, limiting the ability
      of Bcl-2 to prolong cell survival. In the early maturation stage, Bax staining
      faded while the immunoreactivity for Bcl-2 increased. Evidence of distinct
      apoptosis was reduced in the early maturation stage ameloblasts. When related to
      the occurrence of apoptosis during amelogenesis, the relative intensity of
      expression of Bax and Bcl-2 changed in a pattern consistent with that observed in
      other cell lines. This indicates that these proteins play essential roles in the
      process of amelogenesis, as predicted by their proposed mechanisms of action in
      the control of apoptosis.

PMID- 11311204
TI  - Representation of human masseter motor unit action potentials on the EMG and its
      implication for trigeminal reflex investigation.
AB  - The trigeminal reflexes have very short pathways, creating accuracy problems when
      investigating their characteristics (latency, threshold, duration and amplitude).
      This is due to the potential for overlap of multiple evoked responses occurring
      in close succession. The aim of this study was to demonstrate the influence that
      individual motor unit action potential (MUAP) shape and duration can have on
      recordings of trigeminal reflex activity. MUAP profiles were developed for 48
      motor units (3-6 units/subject) using intramuscular multi-unit recording, and 23
      motor units (1-6 units/subject) using surface electromyography (SEMG) in 13
      subjects (six male, seven female, aged 20-73 years). The MUAP data showed age
      related characteristics, which would affect reflex recordings. MUAPs of older
      subjects tended to be longer in duration and multiphasic in shape, whilst younger
      subjects demonstrated shorter-duration action potentials, with a biphasic shape.
      It is recommended that the MUAP profile must be considered in order to overcome
      the methodological challenges unique to the orofacial region.

PMID- 11311205
TI  - Society of Biological Psychiatry 56th annual meeting. May 3-5, 2001. New Orleans,
      Louisiana, USA. Abstracts.

PMID- 11311209
TI  - Growth inhibitory effect of green tea extract and (-)-epigallocatechin in Ehrlich
      ascites tumor cells involves a cellular thiol-dependent activation of mitogenic
      activated protein kinases.
AB  - The effect of green tea extract (GTE) in Ehrlich ascites tumor cells (EATC) was
      studied with respect to changes in the intracellular kinase system involving
      mitogen-activated protein kinases (MAPKs) and cellular thiol. We have previously
      shown a reduction in viability of EATC and tyrosine phosphorylation of 42 and 45
      kDa proteins by GTE and its polyphenolic component, Epigallocatechin (EGC) (D.O.
      Kennedy, S. Nishimura, T. Hasuma, Y. Yoshihisa, S. Otani, I. Matsui-Yuasa,
      Involvement of protein tyrosine phosphorylation in the effect of green tea
      polyphenols on Ehrlich ascites tumor cells in vitro, Chem. Biol. Interact. 110
      (1998) 159-172). Furthermore, GTE and EGC significantly decreased both cellular
      non-protein and protein sulfhydryl levels in EATC, but replenishing thiol stores
      with N-acetylcysteine (NAC) caused a recovery in cell viability, and therefore SH
      groups were identified as a novel target of green tea cytotoxicity (D.O. Kennedy,
      M. Matsumoto, A. Kojima, I. Matsui-Yuasa, Cellular thiol status and cell death in
      the effect of green tea polyphenols in Ehrlich ascites tumor cells, Chem. Biol.
      Interact. 122 (1999) 59-71). In this study, we have observed the stimulation of
      three forms of MAPK, namely ERK1/2, JNK/SAPK and p38, by EGC, which were dose and
      time-dependent. These MAPK stimulations were found to be cellular thiol status
      dependent events as NAC reversed these stimulations. Furthermore, inhibition of
      the p38 MAPK pathway using the p38 inhibitor SB203580 caused a marked dose
      dependent reduction in the decrease in cell viability caused by EGC treatment.
      Inhibiting the Erk1/2 MAPK pathway using the MEK inhibitor PD098059 caused a
      slight change in the decrease in cell viability by EGC. These may suggest that
      the cytotoxicity associated with EGC was more associated with the other MAPKs
      than with ERK1/2. This may be the first study of its kind providing a novel
      evidence of a role for different forms of MAPKs in the antitumor effect of green
      tea polyphenols, especially EGC, in Ehrlich ascites tumor cells.

PMID- 11311210
TI  - Porphyric enzymes in hamster Harderian gland, a model of damage by porphyrins and
      their precursors. A chronobiological study on the role of sex differences.
AB  - The Syrian hamster Harderian gland (HG), representing a highly porphyrogenic
      organ, was used as a model system for studying physiologically occurring damage
      of biomolecules by porphyrins and their precursors, phenomena associated with
      from the pathological situation of porphyrias. The species used exhibits the
      peculiarity of much higher porphyrogenesis in females than in males, offering
      possibilities for comparison of effects by different porphyrin levels in one
      species. Since concentrations of free, and therefore, radical-generating
      porphyric metabolites are difficult to determine in the presence of high amounts
      of secreted and crystallizing porphyrins, which are, moreover, mainly surface
      reactive, and since indications existed for temporal changes in the oxidative
      stress caused by these molecules, the following approach was chosen: in HGs of
      both females and males, activities of the relevant porphyric enzymes, delta
      aminolevulinate synthase (ALA-S), delta-aminolevulinate dehydratase (ALA-D) and
      porphobilinogen deaminase (PBG-D), were determined throughout the circadian
      cycle. Results were compared with the temporal patterns of lipid peroxidation and
      protein damage in the same glands. In females, a strong correspondence was
      observed between protein carbonyl and lipid peroxidation, peaking at the end of
      both photophase and scotophase; maximal activities of the three porphyric enzymes
      ALA-S, ALA-D, and PBG-D either coincided or slightly preceded the peaks of
      oxidative damage. In males, lower enzyme activities, especially in PBG-D, were
      associated with weakly expressed rhythmicity. Correspondingly, lipid peroxidation
      was lower and exhibited a smaller rhythm amplitude; protein carbonyl of males
      showed a temporal pattern differing from that of females, with regard to
      amplitude and phasing. These data are in agreement with morphological
      observations demonstrating particularly severe cell damage in the female HG under
      normal conditions.

PMID- 11311211
TI  - Soluble and membrane-bound acetylcholinesterases in Mytilus galloprovincialis
      (Pelecypoda: Filibranchia) from the northern Adriatic sea.
AB  - Three forms of acetylcholinesterase (AChE) were detected in samples of the
      bivalve mollusc Mytilus galloprovincialis collected in sites of the Adriatic sea.
      Apart from the origin of the mussels, two spontaneously soluble (SS) AChE occur
      in the hemolymph and represent about 80% of total activity, perhaps hydrolyzing
      metabolism-borne choline esters. These hydrophilic enzymes (forms A and B)
      copurified by affinity chromatography (procainamide-Sepharose gel) and were
      separated by sucrose gradient centrifugation. They are, respectively, a globular
      tetramer (11.0-12.0 S) and a dimer (6.0-7.0 S) of catalytic subunits. The third
      form, also purified from tissue extracts by the same affinity matrix, proved to
      be an amphiphilic globular dimer (7.0 S) with a phosphatidylinositol tail giving
      cell membrane insertion, detergent (Triton X-100, Brij 96) interaction and self
      aggregation. Such an AChE is likely functional in cholinergic synapses. All three
      AChE forms show a good substrate specificity and are inactive on
      butyrylthiocholine. Studies with inhibitors showed low inhibition by eserine and
      paraoxon, especially on SS forms, high sensitivity to 1,5-bis(4
      allyldimethylammoniumphenyl)-pentan-3-one dibromide (BW284c51) and no inhibition
      with propoxur and diisopropylfluorophosphate (DFP). The ChE forms in M.
      galloprovincialis are possibly encoded by different genes. Some kinetic features
      of these enzymes suggest a genetic polymorphism.

PMID- 11311212
TI  - Characterization of biotransformation enzyme activities in primary rat proximal
      tubular cells.
AB  - The proximal tubule is a frequent target for nephrotoxic compounds due to it's
      ability to transport and accumulate xenobiotics and their metabolites, as well as
      by the presence of an organ-selective set of biotransformation enzymes. The aim
      of the present study was to characterize the activities of different
      biotransformation enzymes during primary culturing of rat proximal tubular cells
      (PT cells). Specific marker substrates for determining cytochrome P450 (CYP450)
      activity of primary cultured PT cells include 7-ethoxyresorufin (CYP1A1),
      caffeine (CYP1A), testosterone (CY2B/C, CYP3A), tolbutamide (CYP2C) and
      dextromethorphan (CYP2D1). Activities of the CYP450 isoenzymes decreased
      considerably during culture with the greatest loss in activity within 24 h of
      culture. In addition, expression of CYP450 apoprotein, including CYP1A, CYP2C,
      CYP2D, CYP2E and CYP4A, was detected in microsomes from freshly isolated PT cells
      by immunoblotting using specific antibodies. CYP2B and CYP3A apoprotein could not
      be detected. Activity of the phase II biotransformation enzymes GST, GGT, beta
      lyase and UGT was determined with 1-chloro-2,4-dinitrobenzene, L-glutamic acid
      gamma-(7-amido-4-methyl-coumarin), S-(1,1,2,2-tetrafluoroethyl)-L-cysteine and 1
      naphthol, respectively, as marker substrates. Activity of the phase II enzymes
      remained more stable and, in contrast to CYP450 activity, significant activity
      was still expressed after 1 week of PT cell culture. Thus, despite the obvious
      advantages of PT cells as an in-vitro model for studies of biotransformation
      mediated toxicity, the strong time dependency of especially phase I and, to a
      lesser extent, phase II biotransformation activities confers limitations to their
      application.

PMID- 11311213
TI  - The role of glutathione reductase in the cytotoxicity of chromium (VI) in
      isolated rat hepatocytes.
AB  - Chromium (VI) is an environmental and occupational carcinogen, and it is accepted
      that intracellular reduction is necessary for DNA damage and cytotoxicity. We
      have investigated the interaction of Cr(VI) with hepatocytes in vitro to
      determine the contribution of various hepatic enzymes to the reduction of Cr(VI).
      Cr(VI) caused a dose-dependent decrease in cell viability and intracellular
      reduced glutathione (GSH) levels between 100 and 500 microM within 3 h exposure
      of hepatocytes. Both DT-diaphorase and cytochrome P450 play only a minor role in
      detoxifying Cr(VI) and/or its metabolites. (GSH) appears to act as a non
      enzymatic reductant, reducing Cr(VI) to a toxic form. The evidence for this is
      two-fold. Firstly, GSH was depleted during the metabolism of Cr(VI) and,
      secondly, pretreatment of the cells with diethylmaleate to deplete GSH levels,
      partially protected the cells from Cr(VI) toxicity. Glutathione reductase appears
      to play an important role in the enzymatic reduction of Cr(VI) as inhibition of
      this enzyme by carmustine (BCNU) markedly protected the cells from cytotoxicity.

PMID- 11311214
TI  - Comparison of the elimination between perfluorinated fatty acids with different
      carbon chain length in rats.
AB  - Elimination in urine and feces was compared between four perfluorinated fatty
      acids (PFCAs) with different carbon chain length. In male rats,
      perfluoroheptanoic acid (PFHA) was rapidly eliminated in urine with the
      proportion of 92% of the dose being eliminated within 120 h after an
      intraperitoneal injection. Perfluorooctanoic acid (PFOA), perfluorononanoic acid
      (PFNA) and perfluorodecanoic acid (PFDA) was eliminated in urine with the
      proportions of 55, 2.0 and 0.2% of the dose, respectively. By contrast, four
      PFCAs were eliminated in feces with the proportion of less than 5% of the dose
      within 120 h after an injection. In female rats, the proportions of PFOA and PFNA
      eliminated in urine within 120 h were 80% and 51% of the dose, respectively,
      which were significantly higher compared with those in male rats. There was the
      tendency that PFCA with longer carbon chain length is less eliminated in urine in
      both male and female rats. Fecal elimination of PFCAs was not different between
      PFCAs in female rats and comparable to those in male rats. The rates of biliary
      excretion of PFCAs in male rats were slower than those in female rats. Sex
      related difference in urinary elimination of PFOA was abolished when male rats
      had been castrated. On the contrary, treatment with testosterone suppressed the
      elimination of PFOA in urine in both castrated male rats and female rats. The
      effect of testosterone was in a time- and dose-dependent manner. These results
      suggest that PFCAs are distinguished by their carbon chain length by a renal
      excretion system, which is regulated by testosterone.

PMID- 11311215
TI  - N-Nitrosomorpholine induced alterations of unscheduled DNA synthesis,
      mitochondrial DNA synthesis and cell proliferation in different cell types of
      liver, kidney, and urogenital organs in the rat.
AB  - In order to measure rates of unscheduled DNA synthesis (UDS), mitochondrial DNA
      synthesis, and cell proliferation, i.e. factors relevant in the early phase of
      carcinogenesis, young rats received by gavage 200 mg/kg N-nitrosomorpholine (NNM)
      or vehicle (distilled water), and were injected with 3H-thymidine 24 h later.
      Autoradiographs from liver, kidney, urethra, prostate, seminal vesicle, and
      ductus deferens were prepared from deparaffinized sections, using a 250-day
      exposure time. In the liver, UDS was at least doubled in 2n and 4n hepatocytes.
      Approximately 3% of these hepatocytes exhibited a fourfold increase in UDS. Such
      strongly labeled cells were only observed in the liver following NNM exposure.
      With the exception of renal epithelial cells of the proximal tubule, UDS in
      epithelial cells of bladder, urethra, ductus deferens, seminal vesicle and
      prostate was decreased in NNM-exposed rats. Mitochondrial DNA synthesis and cell
      proliferation were significantly increased only in hepatocytes, and were
      decreased in all other monitored organs in NNM-exposed rats. The strongly
      increased UDS and more moderately increased mitochondrial DNA synthesis in a
      subgroup of hepatocytes suggest that possibly some unrepaired damage persists in
      the DNA of these cells. The latter cells may be the precursors of so-called foci
      of hepatocellular alteration, which appear later during the process of
      carcinogenesis. The increased UDS but decreased rate of proliferation in the
      renal proximal tubule cells might be related to renal carcinogenesis which is
      observed in NNM-exposed rats after a long latency period.

PMID- 11311216
TI  - The continuing professional development of the Canadian Society of Clinical
      Chemists and the Canadian Academy of Clinical Biochemists.
AB  - The Canadian Society of Clinical Chemists (CSCC) and the Canadian Academy of
      Clinical Biochemistry (CACB) have recently implemented a new professional
      development program for its 400 members. The program's goals are: to evaluate and
      recognize professional development based on self-determined needs, interests, and
      learning preferences; and to ensure that qualified professionals directing
      clinical biochemistry laboratories have adequate basic and current knowledge to
      function competently in their profession. Involvement in the program is currently
      voluntary and based on a 3-year cycle during which time participants must earn a
      minimum of 150 credits from at least 3 of 8 categories' learning activities. Of
      these activities: four are related to updating knowledge (Formal Group Learning
      related to Laboratory Medicine, Other Formal Group Learning, Self-Directed
      Learning, Self-Assessment); three are related to the maintenance and
      implementation of practice skills (Service Associated Learning, Teaching, Change
      in Practice); and one is related to the advancement of knowledge (Publications
      and Presentations). One credit is defined as one hour of continuing professional
      development activity. At the end of each year, members document their activities
      by submitting a 4 page Annual Summary of Activities (ASA) form. The cost of
      coordinating the program is minimal as it is administered by a steering committee
      and smaller working committees, all of whom are voluntary. A basic assumption of
      our program is that self-management of professional development (PD) is an
      important prerequisite and indicator of maintenance of competence. By recognizing
      learning through a number of activities and outcomes, it is anticipated that our
      program will promote an overall improvement in the quality of Laboratory Medicine
      throughout Canada.

PMID- 11311217
TI  - Correlation between total homocysteine, low-density lipoprotein cholesterol and
      high-density lipoprotein cholesterol in the serum of patients with myocardial
      infarction.
AB  - OBJECTIVES: Determine the Low-density lipoprotein cholesterol (LDL-C), High
      density lipoprotein cholesterol (HDL-C) and serum total homocysteine in
      myocardial infarction patients and control subjects. DESIGN AND METHODS: The
      study group consisted of 126 patients 67 male, and 59 females, aged 29-73 (mean
      48.65 +/- 3.81) years. The entry criteria for the patient group was typical or
      atypical chest pain, unequivocal changes in the electrocardiogram. The control
      group consisted of 135 normal volunteers, 71 male and 64 females, age 21-63 (mean
      42.73 +/- 5.79) years. Measurement of serum total homocysteine was performed
      using gas chromatography. Measurement of Low-density lipoprotein cholesterol, and
      High-density lipoprotein cholesterol were performed using spectrophotometer.
      RESULTS: Patients with myocardial infarction were found to have higher serum
      total homocysteine levels than controls, (P < 0.05). Serum total homocysteine
      levels were significantly correlated with low-density lipoprotein cholesterol and
      high-density lipoprotein cholesterol. There was a negative correlation between
      total homocysteine and HDL-C levels (P < 0.05, r = -0.93). There was a positive
      correlation between total homocysteine and LDL-C levels (P < 0.05, r = 0.98).
      CONCLUSIONS: The above mentioned findings suggest the potential usefulness of LDL
      C, HDL-C and serum total homocysteine as prognostic markers in myocardial
      infarction patients. These findings should influence future studies on the
      etiology and pathogenesis of myocardial infarction.

PMID- 11311218
TI  - Rapid detection of a common dihydropyrimidine dehydrogenase mutation associated
      with 5-fluorouracil toxicity and congenital thymine uraciluria using fluorogenic
      hybridization probes.

PMID- 11311219
TI  - Effect of anticoagulants and storage temperatures on stability of plasma and
      serum hormones.
AB  - OBJECTIVES: To determine the effect of different anticoagulants and storage
      conditions on the stability of hormones in plasma and serum. DESIGN AND METHODS:
      Human blood samples were collected from volunteers into EDTA, lithium heparin,
      sodium fluoride/potassium oxalate, or tubes without anticoagulant, plasma and
      serum left at -20 degrees C, 4 degrees C or 30 degrees C for 24 and 120 hours
      then assayed for ACTH, aldosterone, alpha-subunit, AVP, CRH, C-peptide,
      estradiol, FSH, glucagon, GH, IGF-1, IGFBP-3, insulin, leptin, LH, PPP, PTH,
      prolactin and VIP, or at room temperature for 0 to 72 hours (BNP, NT-BNP)(n = 6
      per condition). RESULTS: The anticoagulant altered the measured concentrations
      for 9 hormones when compared to EDTA. All hormones except ACTH were stable for >
      120 hours in EDTA or fluoride at 4 degrees C, but only 13 hormones were stable in
      all anticoagulants. At 30 degrees C, 8 hormones were stable for > 120 hours in
      EDTA, and 3 hormones in all anticoagulants. BNP and NT-BNP were stable for < 24
      hours when stored in EDTA or heparin at room temperature. DISCUSSION: Storage of
      samples in EDTA plasma at 4 degrees C is suitable for most hormones (except ACTH)
      for up to 120 hours.

PMID- 11311220
TI  - Genetic determination of plasma lipids and insulin in the Czech population.
AB  - OBJECTIVES: To evaluate the association between plasma lipids and insulin and
      variation in the genes for apolipoproteins (APO) E (CfoI), B
      (insertion/deletion), C1 (HpaI), and C3 (C-482T, C3238G) in a population-based
      Czech Slavonic study. DESIGN AND METHODS: In 131 men and 154 women, polymorphisms
      were investigated using PCR. In the same subjects plasma lipid levels and insulin
      were measured. RESULTS: In the women, carriers of the e4 allele had higher apoB
      (p = 0.03) and triglyceride (p = 0.03) compared to e3 homozygotes, whereas in the
      men, the effect of the e4 allele was seen on total cholesterol (p = 0.02), LDL
      cholesterol (p = 0.003) and apoB (p = 0.001). Compared with SP27 (insertion)
      homozygotes of the APOB polymorphism, women SP24 (deletion) homozygotes had
      higher levels of total (p = 0.003) and LDL cholesterol (p = 0.007) and apoB (p =
      0.05). No significant effect was seen in the men. Women homozygous for the APOC3 
      482T allele had higher insulin levels than -482C homozygotes (p = 0.03). Men
      homozygous for APOC3 -482T allele have the highest plasma triglyceride level (p =
      0.02). The APOC1 polymorphism exhibited no significant effect on any of the
      parameters studied. CONCLUSIONS: In this sample, variation at the APOE, APOB and
      APOC3 genes play a role in determining plasma levels of insulin and lipids, and
      emphasize the importance of gender-associated effects in the genetic
      determinations.

PMID- 11311221
TI  - The distribution of major lymphocyte subsets in cord blood is associated with its
      pH.
AB  - OBJECTIVES: To assess in venous cord blood the distribution of major lymphocyte
      subsets according to pH and medications used during labor. DESIGN AND METHODS:
      Venous cord blood was sampled immediately after labor from 70 newborns (35 males
      and 35 females) delivered vaginally. Lymphocytes were immunophenotyped by flow
      cytometry and pH was measured using the AVL 900 automated blood gas analysis
      system. Data on birth weight, gestational age at delivery, length of labor,
      presence of stained amniotic fluid, medications used during labor, maternal risk
      factors, age and parity were collected. RESULTS: The percentage of T lymphocytes
      decreased while the percentage of NK lymphocytes increased with decreasing pH
      over the whole range of pH values. The proportions of T and NK lymphocytes were
      associated with the administration of neuroplegics, spasmolytics or
      dihydroergotoxin in the first stage of labor. CONCLUSIONS: Cord blood pH and
      labor-associated variables should be taken into account to adequately interpret
      the profile of major lymphocyte subsets as a marker of the effect of different
      prenatal factors on the immune system of neonates.

PMID- 11311222
TI  - The evaluation of lipid peroxidation and adenosine deaminase activity in patients
      with Behcet's disease.
AB  - OBJECTIVE: Despite unknown etiology, immunologic alterations and neutrophil
      hyperfunctions may be involved in the etiopathogenesis of Behcet's Disease (BD).
      The purpose of the study was to investigate whether adenosine deaminase (ADA)
      activity, accepted as a nonspecific marker of T lymphocyte activation, may have a
      potential role in BD, and also may be related to the production of reactive
      oxygen species (ROS) by neutrophils. DESIGN AND METHODS: ADA activities and
      malondialdehyde (MDA; endproduct of lipid peroxidation induced by ROS) levels in
      both plasma and erythrocytes were spectrophotometrically measured in 25 patients
      with BD and also in 25 healthy controls. RESULTS: ADA activity was found to be
      higher in plasma, but lower in erythrocytes; plasma and erythrocyte MDA levels
      were higher in BD patients than those of controls. In addition, plasma ADA
      activity was positively related to MDA levels in both plasma (p < 0.05) and
      erythrocytes (p < 0.01). There was also positive correlation between MDA levels
      (p < 0.05), but negative correlations between ADA activities (p < 0.01) and also
      between ADA and MDA values in erythrocytes (p < 0.01) of BD patients. CONCLUSION:
      These findings may provide some evidence for a potential role of T lymphocyte
      activation in BD as reflected by increased plasma ADA activity, and for the
      presence of possible interrelationship between activated T cells and neutrophil
      hyperfunctions, such as ROS generation, as reflected by increased MDA levels.

PMID- 11311223
TI  - Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption
      markers.
AB  - In this study we evaluated the routine practice and clinical application of serum
      crosslaps to urinary-crosslaps, -N-telopeptide-related fraction of type 1
      collagen, -deoxpyridinoline, -totalpyridinoline and serum osteocalcin. The
      utility of both the serum and urine immunoassays for bone formation and
      resorption marker were tested in a cohort of 593 female and male patients from
      our outpatient clinic for osteology and rheumatology and compared to important
      osteoporosis risk factors like age, gender, E2 deficiency, bone density and
      chronic renal failure. The biochemical maker of bone formation, serum osteocalcin
      exhibit significant correlations to all five tested serum and urinary markers of
      bone resorption (p < 0.0001) crosswise to all different groups of patients. The
      group of chronic renal failure patients showed no significant correlation between
      the tested bone turnover parameters and the serum creatinine level except a
      significant increase and correlation for serum crosslaps and for the ratio of
      serum and urinary crosslaps. Associations between the age of the patients and the
      markers of bone turnover were rather poor. We found a significant, negative
      association between serum and urinary bone turnover markers and bone density and
      were interested, whether in patients with bone density < 2.5 SD an enhanced bone
      turnover could be detected in the same way as for E2 deficiency. Applying a
      discriminant analysis it was possible to discriminate between the patient with BD
      < 2.5 SD and those with BD > 1.0 SD with a sensitivity of 70% and a specificity
      of 65% using serum crosslaps. In case of urinary crosslaps the discriminatory
      power was slightly lower (sensitivity: 65.6%, specificity: 67.5%) and for serum
      osteocalcin the discriminatory power was negligible higher (sensitivity: 79%,
      specificity: 56%). The highly significant correlation between the urinary and
      serum crosslinked peptides by ELISA and serum osteocalcin supports the concept
      that these respective indices of bone formation and resorption both in urine and
      serum reflect a coupled process in vivo with sensitivity and specificity to
      pathological bone density, estrogen deficiency and chronic renal failure.

PMID- 11311224
TI  - Action of dipyridamole and warfarin on growth of human endothelial cells cultured
      in serum-free media.
AB  - OBJECTIVE: To study the anti-proliferative effect of Dipyridamole (anti
      platelet), Dipyridamole with Warfarin, and Warfarin (anticoagulant) alone, in
      human endothelial cells in vitro. DESIGN AND METHODS: Human endothelial cells
      were harvested from umbilical cords. Primary cultures were usually successful.
      However, subculture yields were usually contaminated with smooth muscle cells. We
      have developed an improved method for the isolation of endothelial cells by using
      Collagenase II, coating the culture flask with fibronectin and using serum-free
      media. The endothelial cells were characterised by anti-PECAM-1/PE (CD31) using
      Flow Cytometry with viability of 95% after trypsinization with 0.05% Trypsin and
      1 mM EDTA. Growth and proliferation studies were performed in vitro in the
      presence of 5 microM Dipyridamole, 5 microM Dipyridamole with 5 microM Warfarin,
      5 microM Warfarin alone by cell counts, (3)H-thymidine and (3)H-leucine
      incorporation. RESULTS: The incorporation of (3)H-Leucine at day 6 in each test
      condition revealed no significant change. Control 12678 +/- 2968 CPM,
      Dipyridamole 8698 +/- 189 CPM, Dipyridamole and Warfarin 7541 +/- 413 CPM, and
      Warfarin alone 10711 +/- 732 CPM. With the incorporation of (3)H-Thymidine,
      Dipyridamole alone as well as Dipyridamole with Warfarin reduced the basal
      proliferation rates significantly when compared to controls. Control 14355 +/-
      4441 CPM, Dipyridamole 1100 +/- 152 CPM (p<0.05), Dipyridamole with Warfarin 1092
      +/- 272 CPM (p<0.05). Warfarin alone did not reduce proliferation significantly
      12870 +/- 2677 CPM (NS). CONCLUSIONS: We have developed a method to isolate pure
      endothelial cells from human umbilical cords using Serum-Free Media (SFM). EC
      with high purity was characterised by anti-PECAM-1/PE (CD31) using Flow
      Cytometry. Dipyridamole at a concentration of 5 microM inhibited the
      proliferation of endothelial cells at day 6 by 93%. These techniques can be used
      for routine analysis and proliferation studies.

PMID- 11311225
TI  - Apolipoprotein B as the best predictor of coronary artery disease in Iranian
      normolipidemic patients.
AB  - OBJECTIVES: A relatively high proportion of Iranian patients with coronary artery
      disease (CAD) have normal levels of traditional lipid risk factors and show early
      onset of CAD. In this study we examined the roles of apolipoprotein B (apoB),
      apolipoprotein AI (apoAI) and lipoprotein (a) [LP(a)] in predicting coronary
      heart disease in normolipidemic patients and those with premature CAD (age < or =
      50). DESIGN AND METHODS: Serum levels of apoB, apoAI, and LP(a) were determined
      in a total of 567 Iranian patients who were candidates for coronary angiography.
      A subgroup of 142 patients (93 males, 49 females) with normal levels of classical
      lipid risk factors, and a subgroup of patients (130 males, 71 females) with age
      below 50 years were separately assessed for coronary risk factors. RESULTS: ApoB
      concentrations were significantly higher in patients with CAD (CAD+) relative to
      patients without CAD (CAD-) in the two subgroups. Multiple logistic regression
      after controlling for age and others risk factors showed apoB as the best
      determinant of CAD in the normolipidemic subgroup (OR, 4.3, p < 0.001) and in the
      men aged < or = 50 (OR, 5.7, p < 0.001). ApoB was the best predictor of CAD in a
      subgroup of very young patients (age < or = 40, n = 77, OR, 8.6, p < 0.009).
      There was a significant correlation between severity of atherosclerosis and serum
      apoB concentration in the normolipidemic subgroup (r = 0.22, p < 0.008).
      CONCLUSIONS: Our data indicate that serum concentration of apoB is the best
      discriminating factor to predict the presence or absence of atherosclerosis in
      Iranian normolipidemic individuals and young patients undergoing coronary
      angiography.

PMID- 11311226
TI  - Characterization of cross reactivity by carbamazepine 10,11-epoxide with
      carbamazepine assays.

PMID- 11311227
TI  - Medical allowable imprecision in measuring urinary metanephrines.

PMID- 11311228
TI  - Local DNA demethylation in vertebrates: how could it be performed and targeted?
AB  - In vertebrates, cytosine methylation is an epigenetic DNA modification that
      participates in genome stability and gene repression. Methylation patterns are
      either maintained throughout cell division, or modified by global or local de
      novo methylation and demethylation. Site-specific demethylation is a rather
      elusive process that occurs mainly in parallel to gene activation during
      development. In light of our studies of the glucocorticoid-dependent DNA
      demethylation of the tyrosine aminotransferase gene, we discuss the potential
      biochemical mechanisms allowing DNA demethylation and its targeting to specific
      sequences by transcription factors as well as possible links to DNA replication
      and chromatin remodelling.

PMID- 11311229
TI  - Histone deacetylase complexes: functional entities or molecular reservoirs.
AB  - Recent investigations have allowed the identification of an increasing number of
      distinct nuclear multi-component complexes containing several types of enzymatic
      activity. Many of the complexes containing histone deacetylases are believed to
      control transcription and chromatin remodeling. We suggest here that at least
      some of these abundant complexes are likely to be "molecular reservoirs" of
      dynamic composition that exchange factors with other less abundant and functional
      complexes, according to specific required activities.

PMID- 11311230
TI  - Functional site of bukatoxin, an alpha-type sodium channel neurotoxin from the
      Chinese scorpion (Buthus martensi Karsch) venom: probable role of the
      (52)PDKVP(56) loop.
AB  - Alpha-toxins from scorpion venoms prolong the action potential of excitable cells
      by blocking sodium channel inactivation. We have purified bukatoxin, an alpha
      toxin from scorpion (Buthus martensi Karsch) venom, to homogeneity. Bukatoxin
      produced marked relaxant responses in the carbachol-precontracted rat
      anococcygeus muscle (ACM), which were mediated through the L-arginine-nitric
      oxide synthase-nitric oxide pathway, consequent to a neuronal release of nitric
      oxide. Based on the presence of proline residues in the flanking segments of
      protein-protein interaction sites, we predicted the site between (52)PP(56) to be
      the potential interaction site of bukatoxin. A homology model of bukatoxin
      indicated the presence of this site on the surface. Buka11, a synthetic peptide
      designed based on this predicted site, produced a concentration-dependent nitric
      oxide-mediated relaxant response in ACM. Using alanine-substituted peptides, we
      have shown the importance (53)DKV(55) flanked by proline residues in the
      functional site of bukatoxin.

PMID- 11311231
TI  - A small peptide derived from Flt-1 (VEGFR-1) functions as an angiogenic
      inhibitor.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic stimulator which
      functions through two endothelial specific tyrosine kinase receptors, Flt-1 and
      Flk-1. In this work, we show that an 11-amino acid peptide derived from the
      second immunoglobulin-like domain of Flt-1 functions as an angiogenic inhibitor
      in chick chorioallantoic membrane and inhibited VEGF-induced vascular
      permeability in Miles' assay without binding to VEGF directly. Circular dichroism
      and nuclear magnetic resonance analyses indicate that this peptide forms a stable
      extended structure in solution, presumably beta-sheet structure and is most
      likely existing as a dimer. Our results suggest that this small peptide functions
      as an angiogenic inhibitor by inhibiting VEGF function through a non-VEGF binding
      mechanism.

PMID- 11311232
TI  - Zinc ions inhibit oxidation of cytochrome c oxidase by oxygen.
AB  - Cytochrome c oxidase is a membrane-bound enzyme that catalyses the reduction of
      O2 to H2O and uses part of the energy released in this reaction to pump protons
      across the membrane. We have investigated the effect of addition of Zn2+ on the
      kinetics of two reaction steps in cytochrome c oxidase that are associated with
      proton pumping; the peroxy to oxo-ferryl (P(r)-->F) and the oxo-ferryl to
      oxidised (F-->O) transitions. The Zn2+ binding resulted in a decrease of the F-
      >O rate from 820 s(-1) (no Zn2+) to a saturating value of approximately 360 s(-1)
      with an apparent K(D) of approximately 2.6 microM. The P(r)-->F rate
      (approximately 10[(4) s(-1)] before addition of Zn2+) decreased more slowly with
      increasing Zn2+ concentration and a K(D) of approximately 120 microM was
      observed. The effects on both kinetic phases were fully reversible upon addition
      of EDTA. Since both the P(r)-->F and F-->O transitions are associated with proton
      uptake through the D-pathway, a Zn2+-binding site is likely to be located at the
      entry point of this pathway, where several carboxylates and histidine residues
      are found that may co-ordinate Zn2+.

PMID- 11311233
TI  - An Arabidopsis mutant cex1 exhibits constant accumulation of jasmonate-regulated
      AtVSP, Thi2.1 and PDF1.2.
AB  - Jasmonates (JA) act as a regulator in plant growth as well as a signal in plant
      defense. The Arabidopsis vegetative storage protein (AtVSP) and plant defense
      related proteins thionin (Thi2.1) and defensin (PDF1.2) have previously been
      shown to accumulate in response to JA induction. In this report, we isolated and
      characterized a novel recessive mutant, cex1, conferring constitutive JA
      responsive phenotypes including JA-inhibitory growth and constitutive expression
      of JA-regulated AtVSP, Thi2.1 and PDF1.2. The plant morphology and the gene
      expression pattern of the cex1 mutant could be phenocopied by treatment of wild
      type plants with exogenous JA, indicating that CEX1 might be a negative regulator
      of the JA response pathway.

PMID- 11311234
TI  - Monomeric state and ligand binding of recombinant GABA transporter from
      Escherichia coli.
AB  - The gamma-aminobutyric acid (GABA) transporter from Escherichia coli was
      homologously overexpressed and purified to homogeneity with a yield of 1.0 mg per
      liter culture. The purification procedure consists of a cobalt affinity column,
      proteolytic cleavage of His- and myc-tags, and size-exclusion chromatography. The
      purified transporter exists as a monomer in FOS-Choline 12 detergent, with a
      Stokes radius of 45 A for the protein-detergent complex. In detergent solution
      the protein binds substrates, as indicated by tryptophan fluorescence quenching.
      Its dissociation constants (K(d)) for GABA, muscimol and nipecotic acid are 13.8,
      13.3 and 27.9 microM, respectively. This protein preparation provides ideal
      starting materials for future biochemical, biophysical and structural studies of
      the GABA transporter.

PMID- 11311235
TI  - Human anti-asparaginyl-tRNA synthetase autoantibodies (anti-KS) increase the
      affinity of the enzyme for its tRNA substrate.
AB  - Autoantibodies directed against specific human aminoacyl-tRNA synthetases have
      been associated with a clinical picture including myositis, arthritis,
      interstitial lung disease and other features that has been referred to as the
      "anti-synthetase syndrome". Anti-asparaginyl-tRNA synthetase autoantibodies (anti
      KS), the most recently described anti-synthetase autoantibodies, are directed
      against human cytosolic asparaginyl-tRNA synthetase and neutralize specifically
      its activity. Here we show that these antibodies recognize two epitopes on the
      human enzyme, an N-terminal epitope reactive in immunoblot experiments and a heat
      labile epitope in the catalytic domain. In contrast to the well studied anti-Jo-1
      autoantibodies anti-KS when bound to the synthetase increase the affinity of the
      synthetase for its tRNA substrate and prevent aminoacylation without interfering
      with the amino acid activation step.

PMID- 11311236
TI  - Up-regulation of uncoupling proteins by beta-adrenergic stimulation in L6
      myotubes.
AB  - Catecholamine-induced and beta-adrenergic receptor (beta-AR)-mediated
      thermogenesis in skeletal muscle is a significant component of whole-body energy
      expenditure. Skeletal muscle expresses uncoupling protein (UCP) 2 and UCP3, which
      can dissipate the transmitochondrial electrochemical gradient and thereby may be
      involved in regulation of energy metabolism. We investigated the effects of beta
      AR stimulation on UCP2 and UCP3 expression in L6 myotubes. Stimulation of the
      cells with epinephrine increased the UCP3 mRNA level transiently at 6 h, and also
      the UCP2 mRNA level at 6-24 h. The stimulatory effects of epinephrine were also
      observed in the presence of carbacyclin and 9-cis retinoic acid, and mimicked by
      isoproterenol and salbutamol (beta2-AR agonists), but abolished by propranolol
      and ICI-118,551 (beta2-AR antagonists). Pharmacological and mRNA analyses
      revealed the existence of beta2-AR, but not beta1- and beta3-ARs, in L6 myotubes.
      These results suggested that catecholamines up-regulate UCP2 and UCP3 expression
      through direct action on the beta2-AR in skeletal muscle.

PMID- 11311237
TI  - In vitro ubiquitination of cyclin D1 by ROC1-CUL1 and ROC1-CUL3.
AB  - Overexpression of cyclin D1 has been implicated in a variety of tumors, such as
      breast cancers, gastrointestinal cancers and lymphomas. Both gene amplification
      and protein degradation mediated by ubiquitin (Ub)-dependent proteolysis regulate
      the abundance of cyclin D1. Here we report that ROC1 interacted with all three D
      type cyclins in vivo but did not bind to other cyclins tested. The ROC1-CUL1 and
      ROC1-CUL3, but not ROC1-CUL2, -CUL3 and -CUL4, immunocomplexes promoted
      polyubiquitination of bacterially purified cyclin D1 in vitro. RING finger
      mutations of ROC1 eliminated the Ub ligase activity toward cyclin D1. In all
      cases the ubiquitination of cyclin D1 was accompanied by autoubiquitination of
      the cullins. The results suggest the involvement of ROC1-cullin ligases in cyclin
      D1 ubiquitination and a potential mechanism whereby the cullin subunit is
      ubiquitinated itself while ubiquitinating a substrate.

PMID- 11311238
TI  - Inhibition of mitochondrial protein synthesis promotes autonomous regulation of
      mtDNA expression and generation of a new mitochondrial RNA species.
AB  - Mammalian mitochondria are known to proliferate in response to several stimuli.
      Proliferation requires an increase in expression of genes encoding proteins
      involved in mitochondrial biogenesis, as well as in the replication and
      expression of mitochondrial DNA (mtDNA). In contrast, we report that inhibiting
      mitochondrial protein synthesis causes a modulation in mtDNA gene expression
      without the concomitant increase in proliferative markers. Further, inhibition
      results in the production of a previously unidentified light-strand mitochondrial
      RNA that spans the entire displacement loop, the function of which is currently
      unknown.

PMID- 11311239
TI  - Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases
      (TIMP-1, 2, 3 and 4).
AB  - ADAMTS4 (aggrecanase-1) is considered to play a key role in the degradation of
      aggrecan in arthritides. The inhibitory activity of tissue inhibitors of
      metalloproteinases (TIMPs) to ADAMTS4 was examined in an assay using aggrecan
      substrate. Among the four TIMPs, TIMP-3 inhibited the activity most efficiently
      with an IC(50) value of 7.9 nM, which was at least 44-fold lower than that of
      TIMP-1 (350 nM) and TIMP-2 (420 nM) and >250-fold less than that of TIMP-4 (2
      microM for 35% inhibition). These results suggest that TIMP-3 is a potent
      inhibitor against the aggrecanase activity of ADAMTS4 in vivo.

PMID- 11311240
TI  - Functional disruption of IEX-1 expression by concatemeric hammerhead ribozymes
      alters growth properties of 293 cells.
AB  - The early response gene IEX-1 modulates apoptosis and cell growth in a poorly
      defined fashion. Here, we describe the effect of hammerhead ribozymes
      specifically disrupting IEX-1 expression in 293 cells. Compared to vector
      control, 293 cells exhibit a reduced growth rate and a slowed cell cycle
      progression, when stably transfected with a concatemeric ribozyme construct. In
      addition, these 293 cells were much less sensitive to apoptosis induced by an
      activating Fas/CD95 antibody or by the anti-cancer drugs etoposide and
      doxorubicin. By modulating the cell cycle, IEX-1 might be part of a growth signal
      if favourable growth conditions prevail, whereas under unfavourable conditions,
      i.e. death receptor activation, IEX-1 facilitates apoptosis.

PMID- 11311241
TI  - A synaptojanin-homologous region of Salmonella typhimurium SigD is essential for
      inositol phosphatase activity and Akt activation.
AB  - The Ser-Thr kinase Akt is activated in epithelial cells by Salmonella enterica
      serovar typhimurium. The bacterial effector SigD, which is translocated into host
      cells via the specialized type III secretion system, is essential for Akt
      activation. Here, we investigated the inositol phospholipid substrate preferences
      of SigD. Recombinant SigD preferentially dephosphorylated phosphatidylinositol
      3,5-biphosphate and phosphatidylinositol 3,4,5-triphosphate over other
      phosphatidylinositol lipids. Phosphatidylinositol 3-phosphate was not a
      substrate, suggesting the 5' phosphate moiety is one of the preferred substrates.
      Database searches revealed that SigD bears a small region of homology to the
      mammalian type II inositol 5-phosphatase synaptojanin. Mutation of two conserved
      residues in this region, Lys527 and Lys530, decreased or abrogated phosphatase
      activity, respectively. The Shigella flexneri SigD homologue, IpgD, displayed a
      similar activity in vitro and also activated Akt when used to complement a
      DeltasigD Salmonella strain. A mutation in IpgD at Lys507, analogous to Lys530 of
      SigD, also failed to activate Akt. Thus, we have characterized a region near the
      carboxyl-terminus of SigD which is important for phosphatase activity. We discuss
      how dephosphorylation of inositol phospholipids by SigD in vivo might contribute
      to the activation of Akt.

PMID- 11311242
TI  - The transcriptional regulator, Arg82, is a hybrid kinase with both
      monophosphoinositol and diphosphoinositol polyphosphate synthase activity.
AB  - The Arg82 gene of Saccharomyces cerevisiae encodes a transcriptional regulator
      that phosphorylates inositol 1,4,5-trisphosphate [Saiardi et al. (1999) Curr.
      Biol. 9, 1323-1326]. However, some controversy has surrounded the nature of the
      reaction products. We now show that Arg82 phosphorylates inositol 1,3,4,5
      tetrakisphosphate to inositol pentakisphosphate, which is itself converted to two
      isomers of diphosphoinositol tetrakisphosphate, one of which has never previously
      been identified. One of the diphosphoinositol phosphates was further
      phosphorylated by a yeast cell lysate. We propose that Arg82 is an ancestral
      precursor of two distinct and specific enzyme families: inositol 1,4,5
      trisphosphate kinases and diphosphoinositol polyphosphate synthases.

PMID- 11311243
TI  - APAP, a sequence-pattern recognition approach identifies substance P as a
      potential apoptotic peptide.
AB  - We have previously described a novel cancer chemotherapeutic approach based on
      the induction of apoptosis in targeted cells by homing pro-apoptotic peptides. In
      order to improve this approach we developed a computational method (approach for
      detecting potential apoptotic peptides, APAP) to detect short PAPs, based on the
      prediction of the helical content of peptides, the hydrophobic moment, and the
      isoelectric point. PAPs are toxic against bacteria and mitochondria, but not
      against mammalian cells when applied extracellularly. Among other peptides,
      substance P was identified as a PAP and subsequently demonstrated to be a pro
      apoptotic peptide experimentally. APAP thus provides a method to detect and
      ultimately improve pro-apoptotic peptides for chemotherapy.

PMID- 11311244
TI  - Sub-micellar phospholipid accelerates amyloid formation by apolipoprotein C-II.
AB  - Lipid-free human apolipoprotein C-II (apoC-II) forms amyloid fibrils with
      characteristic beta-structure. This conformation is distinct from the alpha
      helical fold of lipid-bound apoC-II. We have investigated the effect of the short
      chain phospholipid, dihexanoylphosphatidylcholine (DHPC) on amyloid formation by
      apoC-II. The alpha-helical content of apoC-II increases in the presence of
      micellar DHPC (16 mM) and amyloid formation is inhibited. However, at sub
      micellar DHPC concentrations (below 8 mM) amyloid formation is accelerated 6
      fold. These results suggest that individual phospholipid molecules in vivo may
      exert significant effects on amyloid folding pathways.

PMID- 11311245
TI  - Akt mediates insulin induction of glucose uptake and up-regulation of GLUT4 gene
      expression in brown adipocytes.
AB  - Insulin acutely stimulated glucose uptake in rat primary brown adipocytes in a
      PI3-kinase-dependent but p70S6-kinase-independent manner. Since Akt represents an
      intermediate step between these kinases, this study investigated the contribution
      of Akt to insulin-induced glucose uptake by the use of a chemical compound, ML-9,
      as well as by transfection with a dominant-negative form of Akt (DeltaAkt).
      Pretreatment with ML-9 for 10 min completely inhibited insulin stimulation of (1)
      Akt kinase activity, (2) Akt phosphorylation on the regulatory residue Ser473 but
      not on Thr308, and (3) mobility shift in Akt1 and Akt2. However, ML-9 did not
      affect insulin-stimulated PI3-kinase nor PKCzeta activities. In consequence, ML-9
      precluded insulin stimulation of glucose uptake and GLUT4 translocation to plasma
      membrane (determined by Western blot), without any effect on the basal glucose
      uptake. Moreover, DeltaAkt impaired insulin stimulation of glucose uptake and GFP
      tagged GLUT4 translocation to plasma membrane in transiently transfected
      immortalised brown adipocytes and HeLa cells, respectively. Furthermore, ML-9
      treatment for 6 h down-regulated insulin-induced GLUT4 mRNA accumulation, without
      affecting GLUT1 expression, in a similar fashion as LY294002. Indeed, co
      transfection of brown adipocytes with DeltaAkt precluded the transactivation of
      GLUT4-CAT promoter by insulin in a similar fashion as a dominant-negative form of
      PI3-kinase. Our results indicate that activation of Akt may be an essential
      requirement for insulin regulation of glucose uptake and GLUT4 gene expression in
      brown adipocytes.

PMID- 11311246
TI  - Increased alpha3-fucosylation of alpha(1)-acid glycoprotein in patients with
      congenital disorder of glycosylation type IA (CDG-Ia).
AB  - Increased fucosylation of the type (sialyl) Lewis(x) was detected on the acute
      phase plasma protein alpha(1)-acid glycoprotein (AGP) in patients with the
      congenital disorder of glycosylation type IA. This is remarkable, because in
      these patients the biosynthesis of guanosine 5'-diphosphate (GDP)-D-mannose is
      strongly decreased, and GDP-D-mannose is the direct precursor for GDP-L-fucose,
      the substrate for fucosyltransferases. The concomitantly occurring increased
      branching of the glycans of AGP and the increased fucosyltransferase activity in
      plasma suggest that a chronic hepatic inflammatory reaction has induced the
      increase in fucosylation.

PMID- 11311247
TI  - Pulmonary surfactant protein SP-B is significantly more immunoreactive in anionic
      than in zwitterionic bilayers.
AB  - Binding of polyclonal and monoclonal antibodies, quantitated by enzyme-linked
      immunosorbent assay, to porcine SP-B reconstituted in different phospholipid
      bilayers has been used to assess differences in protein structure due to lipid
      protein interactions. SP-B bound significantly more antibodies when it was
      reconstituted in bilayers made of anionic phospholipids (phosphatidic acid,
      cardiolipin, phosphatidylglycerol, phosphatidylinositol or phosphatidylserine)
      than in zwitterionic bilayers (phosphatidylcholine,
      phosphatidylcholine/cholesterol, or phosphatidylethanolamine) or in fatty acid
      micelles (made of salts of palmitic or stearic acids). These differences in
      immunoreactivity can be important in the development of quantitation methods for
      SP-B in clinical samples based on immunological techniques.

PMID- 11311248
TI  - Transcriptional and posttranscriptional regulation of the gene for Dally, a
      Drosophila integral membrane proteoglycan.
AB  - "division abnormally delayed"(dally), a Drosophila member of the glypican family,
      has been implicated in Dpp and Wg signaling. Here, we report the genomic
      structure and regulation of the dally gene. The dally gene is composed of nine
      exons, and its expression is controlled by a TATA-less promoter. Analysis of
      transgenic flies bearing the dally promoter fused to the lacZ reporter gene
      showed that a 371 bp sequence of the dally 5' flanking region was capable of
      mimicking the patterns of dally enhancer trap expression in developing tissues,
      including embryonic epidermis and imaginal discs. The tissue-specific enhancers
      that drive marker gene expression in embryo and the wing disc are mapped in the
      5' upstream region of dally gene. We propose that dally gene expression is also
      regulated posttranscriptionally by controlling the translation efficiency and
      stability of its mRNA.

PMID- 11311249
TI  - Evidence for a position-specific deletion as an evolutionary link between long-
      and short-chain scorpion toxins.

PMID- 11311287
TI  - Visual object recognition in multiple sclerosis.
AB  - Deficits in tasks measuring visual processing have been earlier reported in
      studies of MS. Yet, the nature and severity of visual-processing deficits in MS
      remains unclear. We used a new method in order to measure the different stages of
      visual processing in object recognition: shape recognition, familiarity
      recognition, semantic categorization, and identification with naming. Six two
      choice reaction-time tasks were presented to 30 MS patients and 15 healthy
      controls. The patients were divided into cognitively preserved and cognitively
      deteriorated study groups according to their cognitive status. The purpose was to
      find out whether deficits at specific stages of visual processing can be found in
      cognitively deteriorated MS patients. Cognitively deteriorated MS patients did
      not perform as well as cognitively preserved MS patients or healthy controls.
      They were slower already at the early stage of visual processing where
      discrimination of whole objects from scrambled ones was required. They also had
      higher error rates in tasks requiring object familiarity detection and object
      identification with naming. Thus, cognitively deteriorated MS patients had
      difficulties in visual shape recognition and semantic-lexical processing.
      However, variation of performances was large within both of the patient groups
      indicating that even patients without a generalized cognitive decline may have
      deficits in some stages of the visual processing. We suggest that because of the
      heterogeneity of the patients, every single case needs to be examined separately
      in order to identify the possible deficits in visual processing.

PMID- 11311288
TI  - Plasma thrombin-antithrombin III complex is associated with the severity of
      experimental autoimmune encephalomyelitis.
AB  - Previous studies have shown that activation of blood coagulation and fibrin
      depositions around CNS vessels are observed in animals with experimental
      autoimmune encephalomyelitis (EAE), which provides an animal model for human
      autoimmune demyelinating disorders. We examined the values of peripheral blood
      fibrinogen, thrombin-antithrombin III complex (TAT), fibrinolytic activity, and
      fibrin degradation products in Lewis rats with EAE to elucidate the role of the
      blood coagulation-fibrinolysis system in EAE. Plasma TAT values increased
      immediately prior to development of symptoms, and decreased according to the
      improvement of symptoms. There was significant correlation between TAT values and
      clinical scores of EAE; other markers were not correlated with the symptoms of
      EAE. These results suggest that plasma TAT levels are sensitive markers of the
      severity of EAE, and may be useful clinical indicators for the severity of human
      autoimmune demyelinating disorders.

PMID- 11311289
TI  - Primary lateral sclerosis: further clarification.
AB  - Primary lateral sclerosis (PLS) has been defined as a rare. Non-hereditary
      disease characterized by progressive spinobulbar spasticity, related to the
      exclusive involvement of precentral pyramidal neurons, with secondary pyramidal
      tract degeneration and a preservation of anterior horn motor neurons, the latter
      allowing PLS to be distinguish from amyotrophic lateral sclerosis (ALS). However,
      a clear distinction between the two diseases remains a subject of debate. With
      this in mind, we assessed patients with meeting the previously published criteria
      for PLS in a prospective, longitudinal study. At regular intervals, we analyzed
      various clinical and electrophysiological parameters in nine patients with a
      diagnosis of PLS. We made a deltoid muscle biopsy and PET study.Our results
      provide evidence that degeneration in PLS is not restricted to the upper motor
      neurons but also affects the lower motor neurons. The distinction between ALS and
      PLS is related to the degree and stability of lower motor neuron involvement. In
      view of the similarities with ALS, we consider that PLS may represent a slowly
      progressive syndrome closely related to this disease.

PMID- 11311290
TI  - Meiotic instability of the CAG repeats in the SCA6/CACNA1A gene in two Japanese
      SCA6 families.
AB  - Intergenerational stability of the CAG repeat number has been considered to be a
      specific molecular feature of SCA6 compared with other CAG repeat diseases.
      Nevertheless, we showed meiotic instability of the CAG repeats in the
      SCA6/CACNL1A gene in two Japanese SCA6 families, including de novo expansion. In
      one family, the CAG20 allele expanded to the CAG26 one during paternal
      transmission, and in the other family, the CAG19 allele expanded to the CAG20 one
      during maternal transmission. Although it is controversial as to whether the
      CAG20 allele is pathological or not, this is the first case of haplotype analysis
      proven de novo expansion in SCA6, confirming the derivation of an expanded allele
      from one normal allele. We should carefully follow up the individuals carrying
      the CAG20 allele in our family who show normal neurological and radiological
      findings at present.

PMID- 11311291
TI  - Cyclophosphamide attenuates the degenerative changes induced by CSF from patients
      with amyotrophic lateral sclerosis in the neonatal rat spinal cord.
AB  - Our earlier studies have shown that cerebrospinal fluid (CSF) of patients with
      amyotrophic lateral sclerosis (ALS), when intrathecally injected into the
      neonatal rats, produces an aberrant phosphorylation of neurofilaments (NF) in the
      ventral horn neurons and reactive astrogliosis in the spinal cord. We wanted to
      investigate the effect of cyclophosphamide in the spinal cords of neonatal rats
      exposed to ALS-CSF. A single dose (5 microg in 5 microl saline) of
      cyclophosphamide was injected, 24 h after the administration of CSF samples from
      ALS and non-ALS neurological patients into the spinal subarachnoid space of 3-day
      old rat pups. Rats were sacrificed after a period of 24 h, and stained with
      antibodies against the phosphorylated NF (SMI-31 antibody) and glial fibrillary
      acidic protein (GFAP). Cyclophosphamide treatment resulted in a 50% decrease in
      the number of SMI-31 stained neuronal soma in ventral horns of spinal cords of
      ALS-CSF exposed rats. This was accompanied by a decrease in the number of GFAP
      immunoreactive astrocytes. Furthermore, lactate dehydrogenase (LDH) activity was
      also decreased significantly, following cyclophosphamide treatment. These results
      suggest that cyclophosphamide could exert a neuroprotective effect against the
      neurotoxic action of factor(s) present in the ALS-CSF.

PMID- 11311292
TI  - Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory
      polyneuropathy and inclusion body myositis.
AB  - We report favorable results of the long term use of mycophenolate in the
      treatment of three patients with myasthenia gravis (MG), two patients with
      chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with
      secondary polymyositis (PM), and one patient with inclusion body myositis (IBM).
      Side effects were mild. Mycophenolate appears to be a useful addition to the
      armamentarium of immunosuppressants for treatment of chronic immunologically
      mediated neuromuscular diseases.

PMID- 11311293
TI  - A study of interleukin-1 cluster genes in susceptibility to and severity of
      multiple sclerosis.
AB  - In this explorative study, interleukin-1 (IL-1) receptor antagonist (IL-1RA;
      polymorphism of variable number of tandem repeats: VNTR), IL-1alpha (-889), IL
      1beta (-511) and IL-1beta (+3953) polymorphisms were studied in relation to
      susceptibility to and severity of multiple sclerosis (MS), in 93 MS patients and
      400 normal controls. No associations were found for any polymorphisms, alone or
      in combination. However, in our MS cohort, females were found to be IL-1RA allele
      2 carriers more frequently than males (33/49 vs. 16/44, p = 0.0028). Using a
      cohort of 109 controls, IL-1RA allele 2 carriers were more frequently women with
      MS than control women (33/49 vs. 23/43, odds ratio (OR) = 2.19, 95% confidence
      interval (CI) 1.02-4.72, p = 0.043, P(C) = ns). The data suggest that the IL-1
      cluster genes make no major contribution to MS, but the tentative association
      between IL-1RA allele 2 and susceptibility of MS in women warrants further
      studies.

PMID- 11311294
TI  - A neuropathological study of the disturbance of the nigro-amygdaloid connections
      in brains from patients with dementia with Lewy bodies.
AB  - We neuropathologically and immunohistochemically investigated characteristics of
      the central amygdaloid nucleus lesion and its relationship with the substantia
      nigra lesion in dementia with Lewy bodies (DLB) brains. Nine DLB, four
      Parkinson's disease (PD) and four Alzheimer-type dementia (ATD) cases were
      examined. The degree of neuronal loss in the substantia nigra was (+)-(+++) in
      DLB cases, (+++) in PD cases and (+) in ATD cases. All DLB cases showed spongy
      change and ubiquitin-positive spheroids in the central nucleus. The degree of
      spongy change was (+)-(+++) in DLB cases, (+) in PD cases and (-)-(+) in ATD
      cases, which was correlated with the degree of neuronal loss in the substantia
      nigra in DLB cases. The number of ubiquitin-positive spheroids was parallel to
      the degree of spongy change. The central nucleus receives dense dopaminergic
      fibers from the substantia nigra. Many ubiquitin-positive spheroids were also
      positive to alpha-synuclein and tyrosine-hydroxylase, suggesting that they derive
      from the degeneration of terminal or distal axons of Lewy body-bearing
      dopaminergic neurons in the substantia nigra. The disturbance of the dopaminergic
      connections from the substantia nigra to the central nucleus may be responsible
      for psychotic symptoms in DLB patients.

PMID- 11311295
TI  - Anti-Yo-associated paraneoplastic cerebellar degeneration in a man with gastric
      adenocarcinoma.
AB  - Paraneoplastic cerebellar degeneration (PCD) with anti-Yo antibodies is almost
      always associated with ovarian and breast cancer. We describe a man with anti-Yo
      positive PCD and gastric adenocarcinoma. The tumor cells were labeled with anti
      Yo antibodies by immunohistochemistry. High serum titers of anti-Yo antibodies
      were found before surgery and decreased 6 months after resection of the tumor.
      The expression of Yo antigens by the tumor and the decrease in anti-Yo antibody
      titers after its removal suggest that the immune response against the Purkinje
      cells of the cerebellum was triggered by the tumor.

PMID- 11311296
TI  - Hand-centered attentional and motor asymmetries in unilateral neglect.
AB  - On several accounts of "selection for action", acting on a target object among
      distractors requires that irrelevant inputs and responses to these inputs are
      inhibited, and relevant inputs and responses selected. In unilateral neglect
      associated with right-hemisphere lesions, selection processes may be biased
      toward stimuli on the right, as right is usually defined by head and body
      hemispace. In normal subjects performing reaching-to-target tasks, selection may
      be "hand-centered" (Tipper S., Lortie C., Baylis G.C., Journal of Experimental
      Psychology: Human Perception and Performance 18(4) (1992) 891-905) in that
      distractor stimuli close to the hand compete strongly with the target for the
      control of action, causing greater interference than distractors far from the
      hand. We reasoned that in the context of a reaching task, a left-right asymmetry
      in unilateral neglect may be defined with respect to the position of the hand.
      This predicts that target and distractor stimuli to the left of hand (i.e.
      requiring leftward movements for contact) should compete less strongly for the
      control of action than stimuli to the right of the hand. We tested this
      hypothesis by asking eight patients with unilateral neglect (and 12 healthy
      controls) to reach to central targets presented alone and with surrounding
      distractors from left or right start positions. Patients with neglect, but not
      controls, were slower to initiate reaches from right start as compared to left
      start positions. In this context, patients showed interference from distractors
      to the right of the hand and facilitation from distractors to the left of the
      hand. This indicates that a left-right selection asymmetry in neglect may be hand
      centered. These data can be explained on a model of damage to the portion of a
      distributed neuronal population coding movement vectors to stimuli in relatively
      leftward locations.

PMID- 11311297
TI  - Procedural learning deficit in children with Williams syndrome.
AB  - The present study was aimed at evaluating implicit memory processes in subjects
      with Williams syndrome (WS) and comparing them to mental-age (MA) matched normal
      children. For this purpose, tests of verbal and visuo-perceptual explicit memory,
      verbal and visual repetition priming as well as procedural learning tasks were
      administered to 12 WS and 12 MA matched subjects. WS subjects showed a level of
      repetition priming similar to that of MA normal controls. In contrast, WS
      children showed a reduced learning rate in the two procedural tasks. Although
      deficient explicit memory and executive dysfunction cannot be excluded from the
      performance of WS subjects, these results suggest a specific deficit of
      procedural learning in this particular group of mentally retarded children. This
      finding is relevant for our knowledge about the qualitative aspects of the
      anomalous cognitive development in mentally retarded people and the
      neurobiological substrate underlying this development.

PMID- 11311298
TI  - Slowly progressive aphasia: a four-year follow-up study.
AB  - This paper reports the long-term follow-up of GC, a patient with primary
      progressive aphasia of the fluent type. GC presented at onset with an anomia
      characterized by sparing of first letter knowledge, that applied mainly to proper
      names and living categories. No semantic deficits were observed in the first
      stage of the disease, and MRI showed a left temporal lobe atrophy with a gradient
      from the pole to the posterior regions, the latter being less involved. We now
      report the clinical evolution of GC from the 2nd to the 4th year of disease. As
      the disease progressed, the anomia became more severe and the phenomenon of first
      letter sparing was no longer detectable. Also semantic knowledge was gradually
      affected and, eventually, was dramatically lost. However, no other cognitive
      deficits were seen at the last examination. By that time, the temporal atrophy
      shown by MRI was bilateral, although still more evident on the left side.

PMID- 11311299
TI  - Reduced skilfulness of arm motor behaviour among motor stroke patients with good
      clinical recovery: does it indicate reduced automaticity? Can it be improved by
      unilateral or bilateral training? A kinematic motion analysis study.
AB  - Functional cortical reorganisation had been demonstrated to accompany recovery
      from motor stroke. In agreement with a previous study, quantitative kinematic
      analysis of aimed movements in 14 almost completely recovered hemiparetic stroke
      patients and 14 healthy control subjects indicated a reduced skilfulness of both
      the more ballistic initial movement phase and the more feedback-guided late
      homing-in phase of aimed movements. By means of two dual motor tasks it was
      further investigated whether the reduced skilfulness of patients was due to an
      increased attentional demand and thus a reduced automaticity of motor control.
      Interference effects by dual tasks, however, were similar for patients and
      control subjects. Thus, the notion of reduced automaticity could not be supported
      empirically, and reduced skilfulness seemed rather related to residual pyramidal
      motor deficits. By means of a repetitive daily training for 1 week based on the
      Arm Ability Training approach, patients were able to reduce their performance
      deficits in both movement phases significantly. Whether patients practised with
      the affected arm or simultaneously with both the affected and non-affected arm
      only marginally modified outcome, unilateral training being slightly more
      efficacious. These findings demonstrate that even clinically minor residual motor
      deficits can be improved by a structured training for the affected arm.

PMID- 11311300
TI  - Emotion-related learning in individuals prenatally exposed to alcohol: an
      investigation of the relation between set shifting, extinction of responses, and
      behavior.
AB  - The association between deficits in emotion-related learning, conceptual set
      shifting, and behavioral problems was investigated in individuals with
      substantial prenatal alcohol exposure. Twenty subjects with confirmed prenatal
      alcohol exposure (10 of whom were diagnosed as having Fetal Alcohol Syndrome) and
      20 normal controls matched for age, gender, and ethnic background participated.
      The two groups were administered a battery of tests including two tests of
      emotion-related learning (visual discrimination reversal and extinction of reward
      response associations), tests of conceptual set shifting and intellectual
      ability, and behavioral measures. The alcohol-exposed group made fewer reversals
      than the control group in visual discrimination reversal and exhibited more
      variability in extinction. These group differences remained significant after
      controlling for intellectual ability and conceptual set shifting. Variability in
      extinction and two measures of set shifting, perseverative errors on the
      Wisconsin Card Sorting Test and omission errors on reversal learning, were found
      to be robust predictors of parent-rated behavioral problems.

PMID- 11311301
TI  - Deficits in irregular past-tense verb morphology associated with degraded
      semantic knowledge.
AB  - Two distinct mechanisms are often considered necessary to account for generation
      of the past-tense of English verbs: a lexical associative process for irregular
      forms like speak-->spoke, and a rule-governed process ("add -ed") for regular and
      novel forms like talk-->talked and wug-->wugged. An alternative account based on
      a parallel-distributed processing approach proposes that one complex procedure
      processes all past-tense types. In this alternative view, neuropsychological
      dissociations are explained by reduced input from word meaning that plays a
      greater role in successful generation of the past-tense for lower frequency
      irregular verbs, and by phonological deficits that disproportionately affect
      regular and novel forms. Only limited evidence has been available concerning the
      relationship between knowledge of word meaning and verb-tense processing. The
      study reported here evaluated the past-tense verb abilities of 11 patients with
      semantic dementia, a neurodegenerative condition characterised by degraded
      semantic knowledge. We predicted and confirmed that the patients would have
      essentially normal ability to generate and recognise regular (and novel) past
      tense forms, but a marked and frequency-modulated deficit on irregular verbs.
      Across the set of 11 patients, the degree of impairment for the irregular past
      tense was significantly correlated with the degree of comprehension impairment as
      measured by verb synonym judgements. These results, plus other features of the
      data such as the nature of the errors to irregular verbs, are discussed in
      relation to currently developing theories of the language system.

PMID- 11311302
TI  - Passive limb movements improve visual neglect.
AB  - Recent studies have reported that left neglect can be ameliorated during active
      movements of a contralesional limb in the contralesional space. In contrast, a
      passive left hand movement does not seem to induce an amelioration of neglect, at
      least when it is associated to simultaneous active right movement (Robertson IH,
      North N, Neuropsychologia 31 (1993) 293-300). In the present study, we explored
      the possibility that a complex passive movement, such as abduction and adduction
      of the arm, is able to reduce neglect also when it is associated to simultaneous
      active right arm movements. To test this hypothesis neglect patients were
      required to perform an object cancellation test and a line bisection test by
      using the right hand, while the left arm was passively moved. Moreover, we
      verified the possibility that left arm stimulation activates the peripersonal
      more than the extrapersonal space, with the exception of the condition in which
      the far space can be reached by a tool that extends peripersonal space in the far
      space (Farne A, Ladavas E, Neuroreport 11 (2000) 1645-1649). For this reason,
      patients were required to perform the tasks in near (70 cm) and in far (140 cm)
      space by means of a light pen (pointing task) and of a stick (reaching task).
      When the left arm was passively moved the results showed a significant reduction
      of neglect with respect to the baseline condition, and the improvement equally
      affected the near and the far space. A different effect for the near and far
      space was observed in relation to the task (pointing vs. reaching). In the
      pointing task, neglect was more severe in the far than in near space; however,
      this difference disappeared when the patients had to reach objects by means of a
      stick. In conclusion, the present study shows that the entity of improvement of
      visual neglect due to a left passive movement is related to the entity of
      proprioceptive signals specifying left hand position.

PMID- 11311303
TI  - Grip force scaling and sequencing of events during a manipulative task in
      Huntington's disease.
AB  - The aim of the study was to investigate force regulation and sequencing of events
      in Huntington's disease (HD) patients when performing a drawer opening task using
      the precision grip. Results revealed that HD patients used excessive grip force
      levels that were unrelated to the actual task demands. Also, they demonstrated a
      higher grip force value at load force onset in addition to an increased delay
      between initiation of grip force and load (pulling) force. These data indicate a
      deficit in the coordinated activation of both forces due to HD. Furthermore, the
      patients showed bradykinesia along with a prolonged interval between the movement
      phases underlying the task, denoting an impairment in encoding serially ordered
      events. Together, these results illustrate the deteriorating effect of striatal
      pathology on manual function. Accordingly, an amended control of grasping forces
      and serial encoding of movement-related events due to HD are likely to affect the
      proficiency of common manipulative skills.

PMID- 11311304
TI  - Parsing cognition in schizophrenia using saccadic eye movements: a selective
      overview.
AB  - Eye movements provide a behavioural measure of sensorimotor processing and higher
      cognitive functions of the brain. With the development of novel paradigms that
      can be used for the study of various cognitive operations, saccadic eye movements
      in particular, have become increasingly popular. Patients with schizophrenia have
      neurocognitive impairments that can be readily investigated with these paradigms.
      From animal, human lesion and neuroimaging studies, the cerebral centres
      underlying saccadic eye movements have been identified. The areas of the
      prefrontal cortex include the dorsolateral prefrontal cortex, the frontal eye
      fields, the supplementary eye fields, and the anterior cingulate cortex.
      Pathology of saccadic eye movements, therefore, provides information on the
      functional status of the underlying neural circuitry in brain disorders such as
      schizophrenia. In this paper, we evaluate: (i) methodological considerations that
      are central to the design and application of saccadic paradigms; (ii) brain
      activation that is associated with saccadic paradigms; (iii) recent findings in
      healthy subjects and schizophrenic patients; (iv) saccadic abnormalities in other
      psychiatric and neurological disorders and in individuals at risk for developing
      schizophrenia.

PMID- 11311306
TI  - Snorkel breathing in the elephant explains the unique anatomy of its pleura.
AB  - It has been known for over 300 years that the anatomy of the elephant lung is
      unique among mammals in that the pleural cavity is obliterated by connective
      tissue. However no satisfactory explanation has been advanced. Recent studies
      suggest that the elephant has an aquatic ancestry and the trunk may have
      developed for snorkeling. In addition, the modern day elephant is the only mammal
      that can remain submerged far below the surface of the water while snorkeling.
      The resulting differences of pressures within the thorax mean that the small
      blood vessels of the pleura are in great danger of rupturing or causing severe
      edema. The same distribution of pressures occurs when the animal raises water
      inside its trunk prior to drinking although in this case the pressure differences
      are relatively short-lived. Evolution has provided a remarkable solution to this
      problem by replacing the normally delicate parietal and visceral pleurae by dense
      connective tissue, and separating the two pleurae by loose connective tissue to
      allow some sliding movement.

PMID- 11311307
TI  - Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis.
AB  - Bleomycin treatment in rats results in pulmonary fibrosis that is characterized
      by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance
      and a blunting of the Hering-Breuer Inflation Reflex. We examined the impulse
      activity of pulmonary vagal afferents in anesthetized, mechanically ventilated
      rats with bleomycin-induced lung fibrosis during the ventilator cycle and static
      lung inflations/deflations and following the injection of capsaicin into the
      right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch
      receptors (SARs), while it blunted the sensitivity of these receptors to
      increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory
      activity, while it decreased the expiratory activity of rapidly adapting stretch
      receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be
      affected by bleomycin treatment. We conclude that the fibrosis-related shift in
      discharge profile and enhanced volume sensitivity of SARs combined with the
      increased inspiratory activity of RARs contributes to the observed rapid shallow
      breathing of bleomycin-induced lung fibrosis.

PMID- 11311308
TI  - Ventilatory effects of alpha2-adrenoceptor blockade in awake goats.
AB  - We sought to determine the extent to which alpha2-adrenoceptor (alpha2-AR)
      pathways exert a tonic influence on respiratory rhythm under normal physiological
      conditions. The ventilatory effects of alpha2-AR blockade with SKF-86466 were
      examined in awake adult goats. The antagonist effect of SKF-86466 at alpha(2)-ARs
      was evident both as a reversal of the ventilatory disturbances produced by the
      alpha2-AR agonist clonidine (5 microg/kg IV) and as a rightward shift in the
      potency of the agonist-evoked response after SKF-86466 pretreatment. Systemic
      administration of SKF-86466 in cumulative doses (25-250 microg/kg) or as a single
      bolus injection (500 microg/kg) produced dose-dependent increases in breathing in
      all animals. The excitatory effect was primarily mediated by increases in
      respiratory frequency that persisted for at least 120 min after injection (500
      microg/kg). The time course and magnitude of the ventilatory response to SKF
      86466 was similar in carotid body denervated animals. The ventilatory response to
      isocapnic hypoxia but not normoxic hypercapnia was significantly elevated after
      SKF-86466 administration (500 microg/kg). SKF-86466 (25-1000 microg/kg) produced
      dose-dependent increases in heart rate in all animals but did not significantly
      change mean arterial blood pressure at any dose. The results demonstrate that
      alpha2-AR pathways exert a tonic inhibitory influence on respiratory rhythm in
      the awake goat.

PMID- 11311309
TI  - Differential effects of hypercapnia on expiratory phases of respiration in the
      piglet.
AB  - Hypercapnia induces prolongation of expiratory time (TE) during early
      development. In the present study, we determined the response to steady state
      hypercapnia of three neural phases of the total respiratory cycle, inspiration
      (TI), stage 1 or passive expiration, TE-1 and stage 2 or active expiration, TE-2.
      Experiments were performed in decerebrate, vagotomized, spontaneously breathing
      piglets aged 5-10 days. Neural phases of the respiratory cycle were based on
      electrical activities of the thyroarytenoid (TA, laryngeal adductor) and
      triangularis sternii (TS, chest wall expiratory muscle) in relation to diaphragm
      (D) activity. We observed that hypercapnia induced prolongation of both
      expiratory phases. The greater prolongation of TE-1 was associated with an
      increase in TA activity and an increase in laryngeal resistance, which peaked
      early in TE-1, and then progressively decreased. These findings demonstrate that,
      in early postnatal life, a hypercapnia induced increase in respiratory drive is
      associated with centrally mediated prolongation of both phases of expiration, a
      greater prolongation of TE-1, and an increase in laryngeal resistance during post
      inspiration. We speculate that the latter serves to optimize gas exchange by
      reducing large fluctuations in functional residual capacity.

PMID- 11311310
TI  - Dynamics of microvascular oxygen pressure across the rest-exercise transition in
      rat skeletal muscle.
AB  - There exists substantial controversy as to whether muscle oxygen (O2) delivery
      (QO2) or muscle mitochondrial O2 demand determines the profile of pulmonary VO2
      kinetics in the rest-exercise transition. To address this issue, we adapted
      intravascular phosphorescence quenching techniques for measurement of rat
      spinotrapezius microvascular O2 pressure (PO2m). The spinotrapezius muscle
      intravital microscopy preparation is used extensively for investigation of muscle
      microcirculatory control. The phosphor palladium-meso-tetra(4
      carboxyphenyl)porphyrin dendrimer (R2) at 15 mg/kg was bound to albumin within
      the blood of female Sprague-Dawley rats ( approximately 250 g). Spinotrapezius
      blood flow (radioactive microspheres) and PO2m profiles were determined in situ
      across the transition from rest to 1 Hz twitch contractions. Stimulation
      increased muscle blood flow by 240% from 16.6 +/- 3.0 to 56.2 +/- 8.3 (SE) ml/min
      per 100 g (P < 0.05). Muscle contractions reduced PO2m from a baseline of 31.4 +/
      1.6 to a steady-state value of 21.0 +/- 1.7 mmHg (n = 24, P < 0.01). The
      response profile of PO2m was well fit by a time delay of 19.2+/-2.8 sec (P <
      0.05) followed by a monoexponential decline (time constant, 21.7 +/- 2.1 sec) to
      its steady state level. The absence of either an immediate and precipitous fall
      in microvascular PO2 at exercise onset or any PO2m undershoot prior to
      achievement of steady-state values, provides compelling evidence that O(2)
      delivery is not limiting under these conditions.

PMID- 11311311
TI  - Role of nitric oxide (NO) in pulmonary dysfunction associated with experimental
      cirrhosis.
AB  - We examined the functional role of nitric oxide (NO) and nitric oxide synthase
      (NOS) isoforms in the pulmonary dysfunction seen in cirrhosis. Lungs were
      isolated from control and carbon tetrachloride (CCl(4))-induced cirrhotic rats
      and perfused at constant flow with a whole blood mixture. Ventilation with
      hypoxic gas resulted in attenuated hypoxic pulmonary vasoconstriction (HPV) in
      lungs from cirrhotic animals. Administration of the non-selective NOS inhibitor N
      omega-Nitro-L-Arginine (L-NNA) resulted in HPV responses that were not different
      between groups. However, inhibition of inducible nitric oxide synthase (iNOS) did
      not restore cirrhotic HPV responses. Lungs from cirrhotic rats demonstrated
      enhanced endothelial-dependent vasodilation to vasopressin when preconstricted
      with hypoxia but not when preconstricted with thromboxane mimetic. Western blot
      analysis failed to demonstrate differences in pulmonary endothelial NOS (eNOS) or
      iNOS levels between groups. Our data suggest that, while NO may play a role in
      mediating the reduced pulmonary vasoreactivity observed in cirrhosis, other
      vasoactive factors are likely also important modulators of the pulmonary
      dysfunction seen in this disease.

PMID- 11311312
TI  - Development of the pulmonary surfactant system in the green sea turtle, Chelonia
      mydas.
AB  - This study describes the developmental changes in pulmonary surfactant (PS)
      lipids throughout incubation in the sea turtle, Chelonia mydas. Total
      phospholipid (PL), disaturated phospholipid (DSP) and cholesterol (Chol)
      harvested from lung washings increased with advancing incubation, where secretion
      was maximal at pipping, coincident with the onset of pulmonary ventilation. The
      DSP/PL ratio increased, whereas the Chol/PL and the Chol/DSP ratio declined
      throughout development. The phospholipids, therefore, are independently regulated
      from Chol and their development matches that of mammals. To explore whether
      hypoxia could elicit an effect on the development of the PS system, embryos were
      exposed to a chronic dose of 17% O2 for the final approximately 40% of
      incubation. Hypoxia did not affect incubation time, absolute, nor relative
      abundance of the surfactant lipids, demonstrating that the development of the
      system is robust and that embryonic development continues unabated under mild
      hypoxia. Hypoxia-incubated hatchlings had lighter wet lung weights than those
      from normoxia, inferring that mild hypoxia facilitates lung clearance in this
      species.

PMID- 11311314
TI  - Caretaker or undertaker? The role of the proteasome in aging.
AB  - Despite intensive studies, the molecular basis of the decline of protein
      degradation with age still remains unresolved. It is suspected that the
      proteasome is one of the key factors controlling the age-dependent turnover of
      intracellular proteins. This hypothesis is based on the observation that the
      proteasome is a part of the ubiquitin-proteasome pathway, which together with the
      lysosomal pathway constitute the major mechanisms of protein degradation. While
      there are alterations in proteasome structure and function with age, the observed
      changes do not provide a clear mechanism for explaining the decline of protein
      degradation. In addition, there are no consistent changes in the ubiquitination
      system to account for this decline. On the other hand, because of the essential
      role played by the proteasome in the maintenance of cellular homeostasis, the
      observation of age-related changes in structure and function will ultimately be
      demonstrated to contribute to the aging process. The fact that food restriction,
      the only currently available experimental paradigm that can alter the aging
      process, modulates the age-related changes in proteasome structure and function
      provides presumptive evidence that the proteasome is involved in the aging
      process.

PMID- 11311315
TI  - Multidrug resistance gene expression during the murine ontogeny.
AB  - Multidrug resistance (MDR) was described initially for tumor cells which become
      resistant not only to the specific drug to which they are submitted, but also to
      a large range of unrelated drugs. The expression of mdr genes, responsible for
      the phenotype, and their product P glycoprotein (Pgp), is currently under
      intensive study due to their ample distribution in different organisms and their
      possible physiological roles which include protection against xenobiotics. In
      mice, three mdr isoforms expressed in some normal tissues are known. In this
      work, we analyzed by RT-PCR the expression of mdr1, mdr2 and mdr3 in several
      organs of BALB/c and C57BL/6 mice during ontogeny. A considerable variation in
      mdr expression among individuals of the same strain, as well as among different
      organs in individuals of the same age group and among different age groups, was
      detected. We also observed a strong tendency for the expression of a greater
      number of active isoforms in old mice. The large expression range of the mdr
      isoforms point to an important role as a natural defense system.

PMID- 11311316
TI  - A system approach modelling of the three-stage non-linear kinetics in biological
      ageing.
AB  - There is a widely observed non-linear kinetics in the ageing of biological
      systems, which is characterised by three successive stages, (1) the ageing rate
      is firstly high, but decreases quickly to a minimum, from which (2) it remains
      nearly constant during the major part of the process until (3) it starts
      increasing again up to the final collapse of the system. Such kinetics are also
      encountered in the ageing of inert systems. It is shown that a model useful for
      the follow-up of operating inert systems allows to find back typical curves and
      laws related to the ageing of biological systems (mortality rate curves, survival
      curves, growth curves, Gompertz law, ...). In this model, ageing is seen as a
      multifactorial process. The classical concepts of lifespan, longevity and life
      expectancy are given new light using the model, which also gives clues to explain
      both the discrepancy in the age of death of individuals in a given population and
      the wide range of lifespans of species encountered in nature. Finally, the model
      shows in which directions accelerated senescence testing protocols should be
      orientated for a better understanding of the underlying phenomena and for life
      prediction purposes.

PMID- 11311317
TI  - Relationship between NADP-specific isocitrate dehydrogenase and glutathione
      peroxidase in aging rat skeletal muscle.
AB  - The glutathione peroxidase (GPX) system detoxifies hydroperoxides in cells and
      uses NADPH to regenerate reduced glutathione. Enzymatic sources of NADPH in
      skeletal muscle include NADP-specific isocitrate dehydrogenase (ICDP), glucose-6
      phosphate dehydrogenase (G6PD), and malic enzyme (ME). Our purpose was to explore
      the relationship in skeletal muscle between GPX and ICDP along with other NADPH
      generating enzymes as a function of progressive age and muscle fiber-type. Soleus
      (SOL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles were
      extracted from Fischer-344 rats of three different ages: 4 months old (Y); 18
      months old (M); and 24 months old (O). Assays were conducted to determine
      activities of GPX, ICDP, G6PD, and ME along with levels of lipid hydroperoxides.
      GPX activities were significantly greater in RG and WG of old rats than in
      younger. ICDP activities were higher in the WG of old and middle aged rats when
      compared to young adults. GPX and ICDP activities exhibited similar differences
      among the muscles tested (SOL>RG>WG). In contrast, G6PD and ME activities were
      not significantly different across muscles. G6PD activities increased in RG with
      age, but were well over an order of magnitude lower than ICDP in all muscles. ME
      activities were universally lower than ICDP in all muscles, and decreased with
      old age in the WG and RG. Lipid hydroperoxides were significantly higher with
      aging in RG. Significant correlations were found between GPX and ICDP in all
      muscles. Stepwise regression resulted in a model (R(2)=0.82) that included ICDP
      and ME in predicting GPX. In summary, these data are consistent with the
      hypotheses that ICDP is higher in more oxidative fibers, inducible with aging,
      and most closely associated with the glutathione peroxidase system in skeletal
      muscle.

PMID- 11311318
TI  - Aged mice exhibit in vivo defective peripheral clonal deletion of D(b)/H-Y
      reactive CD8(+) T cells.
AB  - We previously reported that T cells from aged mice were resistant to activation
      induced cell death (AICD) in vitro. To determine whether the presence of AICD
      resistant T cells is associated with defects in age-related peripheral clonal
      deletion in vivo, congenic male SCID mice were reconstituted with T cells from
      aged or young female D(b)/H-Y TCR (Tg71) transgenic mice. Compared with
      recipients of young cells, the recipients of T cells from aged mice exhibited a 3
      fold increase in the percentage of autoreactive CD8(+) H-Y antigen-reactive T
      cells as defined by the clonotypic antibody, M33. There were significantly
      increased sera levels of interferon-gamma, a significantly decreased expression
      of FasL by M33(+)CD8(+) T cells, and significantly decreased apoptosis by DNA
      fragmentation staining of the spleen of mice reconstituted with T cells from aged
      mice compared to those from young mice. By day 21, the recipients of T cells from
      aged mice but not young mice, exhibited infiltration of CD3(+) cells into the non
      lymphoid organs. These results indicate that there is defective peripheral
      deletion of the self-reactive T cells derived from aged female Tg71 mice, and
      that failure to delete these cells is associated with the defective T-cell clonal
      deletion in the recipient mice.

PMID- 11311319
TI  - Similarities and dissimilarities of newborn and adolescent rats in the binding
      capacity of thymic glucocorticoid receptors.
AB  - The glucocorticoid receptor of the newborn thymus binds dexamethasone with the
      same specificity, as the adult ones. The best competitors of dexamethasone on the
      glucocorticoid receptor are dexamethasone itself and mifepristone (RU486).
      Estradiol can compete with dexamethasone on the glucocorticoid receptor. This is
      true in the case of newborn or adolescent thymus alike. Allylestrenol can
      slightly compete with dexamethasone on the glucocorticoid receptor in newborn,
      however this does not occur in adolescents. The other ligands - causing
      imprinting or imprinting like phenomenon earlier -- as tocopherol, menadione,
      retinoic acid, vitamin D(3) -- do not compete in vitro with dexamethasone on the
      thymic glucocorticoid receptor in newborn and adolescent animals. Possibilities
      of imprinting mechanism, considering the results are discussed.

PMID- 11311320
TI  - An elevation in the concentration of HLA class I molecules in human blood due to
      ageing.
AB  - The quantification of plasmatic HLA class-I molecules (sHLA-I) was realized by a
      sandwich ELISA using a monomorphic mAb (W6/32). sHLA-I concentration is
      significantly increased in the elderly group (>50 years, 0.429+/-0.301 microg ml(
      1)) as compared to the young group (<50 years, 0.126+/-0.085 microg ml(-1)). The
      variation of sHLA-I content could contribute to the unresponsiveness of ageing
      immune system.

PMID- 11311321
TI  - Immunological restoration and anti-tumor effect by Japanese herbal medicine in
      aged mice.
AB  - We examined the effect of two Japanese herbal medicines (Kampo-Hozai) on
      immunological functions and anti-tumor activity in old mice. Hochu-ekki-to (TJ
      41) was remarkably effective in the restoration of impaired immune functions of
      old mice, in terms of number of T cells and NK cells, and anti-SRBC antibody
      response, while it was not effective in enhancing immune functions of young mice.
      Juzen-taiho-to was also effective in increasing the number of T cells,
      remarkably, and NK cells, slightly, in the aged mice. While a significant
      increase was not observed in young mice. NK activity increased both in young and
      old mice with the treatment of TJ-48. A significant decrease was observed in
      metastatic pulmonary colonies of B16 melanoma cells both in young and old mice
      treated with Juzen-taiho-to for 16 weeks. These results suggested that some of
      Japanese herbal medicines were useful in restoration of impaired immune functions
      of old mice and could be recommended for human elderly.

PMID- 11311323
TI  - Does IFNgamma play a role in neurodegeneration?

PMID- 11311324
TI  - IL-17 and IFN-gamma mRNA expression is increased in the brain and systemically
      after permanent middle cerebral artery occlusion in the rat.
AB  - Brain ischemia is characterized by local inflammation reflected by accumulation
      of inflammatory cells and a multitude of mediators. Among them, cytokines and
      chemokines may influence the inflammatory cascade that follows cerebral ischemia.
      Here we report on brain hemispheric and systemic increase of pro-inflammatory IL
      17 and IFN-gamma, the anti-inflammatory cytokines IL-4 and IL-10, and the
      chemokines IP-10, IL-8 and MIP-2, 1 h to 6 days after permanent middle cerebral
      artery occlusion (pMCAO). IL-17 and IFN-gamma mRNA levels were elevated in the
      ischemic hemispheres of pMCAO-operated rats compared with corresponding
      hemispheres of sham-operated rats. Levels were slightly elevated at 1 h, and
      peaked at 6 days after pMCAO. IL-8 and MIP-2 levels in the ischemic hemispheres
      peaked at 24 h, whereas IP-10 showed a biphasic profile with two peaks at 6 h and
      6 days after pMCAO. IL-4 peaked in the ischemic hemispheres at 6 h, when IL-10
      levels were lower than in sham-operated rats, and IL-10 levels peaked at 2 days
      after pMCAO. Systemically, the numbers of IL-17 and IFN-gamma mRNA expressing
      blood mononuclear cells were elevated already at 1 h after pMCAO, preceding the
      changes in the ischemic hemispheres. Altered levels of IL-17 and IFN-gamma after
      pMCAO may affect outcome of brain ischemia.

PMID- 11311325
TI  - Intracerebroventricular administration of somatostatin prevents and attenuates
      adjuvant arthritis.
AB  - The effects of somatostatin on the development of adjuvant arthritis induced by
      Mycobacterium butyricum were studied. Somatostatin was injected into the lateral
      cerebral ventricle every day for 14 days beginning on the first day of
      mycobacteria inoculation in the preventive group. In the treatment group,
      somatostatin was injected from day 17 until day 30 post-mycobacteria inoculation.
      Arthritis was evaluated by measuring ankle joint circumference and diameter as
      well as microscopic examination of ankle joint sections. Somatostatin profoundly
      inhibited the development of adjuvant arthritis and an anti-inflammatory action
      was observed in the treatment group. These results suggest that somatostatin has
      a central action that can prevent or attenuate symptoms associated with
      arthritis.

PMID- 11311326
TI  - Oral tolerance in experimental autoimmune neuritis (EAN) of the Lewis rat. II.
      Adjuvant effects and bystander suppression in P2 peptide-induced EAN.
AB  - Experimental autoimmune neuritis (EAN) in Lewis rats serves as an animal model of
      human inflammatory demyelinating neuropathies. We previously demonstrated that
      EAN actively induced by immunization with bovine PNS-myelin can be suppressed by
      feeding of myelin. This myelin-specific oral tolerance (OT) was enhanced by
      coapplication of cholera toxin (CT).In the present study, EAN induced by
      immunization with a neuritogenic P2 peptide was completely prevented by precedent
      feeding of the peptide. Oral application of the P2 peptide mediated tolerance as
      efficient as did nasal administration. In contrast to OT by myelin, addition of
      CT completely prevented oral induction of tolerance to peptide-induced EAN, while
      adjuvant feeding alone did not modulate disease. As a possible immunological
      basis to explain the prevention of OT induction by CT, we identified a highly
      enhanced protein-specific in vitro proliferation of splenocytes from antigen/CT
      fed animals compared to those of rats fed with the antigen only. The opposite
      effects of oral CT in combination with proteins versus myelin confirm our former
      assumption that CT augments myelin-induced tolerance by its binding to
      gangliosides present in the myelin but not in the P2 peptide solution, while free
      CT prevents the induction of OT. It is suggested that CT is a useful adjuvant for
      OT if coadministered with myelin, but requires chemical linkage to proteins to
      exert this function. Regulatory lymphocytes orally induced by feeding the protein
      keyhole limpet hemocyanine (KLH) slightly ameliorated peptide-induced EAN via
      bystander mechanisms, but injection of KLH in close proximity to the site of
      peptide-immunization was essential. The restriction of bystander suppression to
      that site in the lymphoid system where neuritogenic T cells are activated may
      limit the impact of OT as a bonafide treatment strategy in human autoimmune
      diseases and underscores the necessity to identify the autoantigens involved.

PMID- 11311327
TI  - Peripheral nerve exposure to HIV viral envelope protein gp120 induces neuropathic
      pain and spinal gliosis.
AB  - Painful sensory neuropathy is a common and debilitating consequence of human
      immunodeficiency virus (HIV). The underlying causes of neuropathic pain are most
      likely not due to direct infection of the nervous system by active virus. The
      goal of this study was to determine whether epineural exposure to the HIV-1
      envelope protein gp120 could lead to chronic painful peripheral neuropathy. Two
      doses of gp120 or BSA control were transiently delivered epineurally via oxidized
      cellulose wrapped around the rat sciatic nerve. Animals were assessed for
      neuropathic pain behaviors at several intervals from 1-30 days following nerve
      surgery. Allodynia and hyperalgesia were observed within 1-3 days following gp120
      and sustained throughout the testing period. The gp120-exposed sciatic nerve
      exhibited early but transient pathology, notably axonal swelling and increased
      tumor necrosis factor alpha (TNF-alpha) within the nerve trunk. In contrast,
      intense astrocytic and microglial activation was observed in the spinal cord, and
      this gliosis persisted for at least 30 days following epineural gp120, in
      parallel with neuropathic pain behaviors. These findings demonstrate that limited
      peripheral nerve exposure to HIV protein can induce persistent painful sensory
      neuropathy that may be sustained and magnified by long-term spinal
      neuropathology.

PMID- 11311328
TI  - Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an
      agonist of peroxisome proliferator-activated receptor-gamma.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the
      nuclear hormone receptor superfamily, plays a critical role in adipocyte
      differentiation and glucose homeostasis. It has been implicated that PPAR-gamma
      functions as a regulator of cellular proliferation and inflammatory responses. In
      the present study, we examined whether troglitazone, a selective PPAR-gamma
      agonists, ameliorated experimental autoimmune encephalomyelitis (EAE) induced by
      administration of myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in
      C57BL/6 mice. We found that troglitazone attenuated the inflammation and
      decreased the clinical symptoms. It was suggested that the amelioration was
      attributed to the attenuation of pro-inflammatory cytokine gene expressions.

PMID- 11311329
TI  - Migration of human granulocytes through reconstituted basement membrane is not
      dependent on matrix metalloproteinase-9 (MMP-9).
AB  - Transmigration of human granulocytes across a basal lamina equivalent was studied
      in vitro. Transwell inserts were coated with Matrigel, a reconstituted basement
      membrane. Granulocytes (2x10(6)) were applied to the upper chamber. As
      chemoattractant interleukin-8 (IL-8; 25 ng/ml) was added to the lower chamber.
      After 1 h of migration, cells were counted in the lower chamber. Specific
      hydroxamate inhibitors of MMPs (BB-3103, Ro 31-9790) or of serine proteases
      (Pefabloc, leupeptin) were added at various concentrations to both chambers
      before the start of migration. Additional experiments were performed with
      alpha(2)-macroglobulin, a natural inhibitor of MMPs and a monoclonal antibody
      which specifically blocks the activity of MMP-9. Migration of granulocytes
      through Matrigel could not be reduced significantly by any of the MMP inhibitors.
      A dose-dependent impairment of transmigration was only found with Pefabloc,
      however, this substance also induced severe morphological changes of the cells.
      The other inhibitor of serine proteases, leupeptin, did not influence migration
      at all.

PMID- 11311330
TI  - Failure of alpha-melanocyte stimulating hormone to attenuate cerebral
      complications in experimental pneumococcal meningitis.
AB  - Alpha-melanocyte-stimulating hormone (alpha-MSH) is an endogenous
      neuroimmunomodulatory peptide that can inhibit a broad range of inflammatory
      mediators known to be involved in the pathophysiology of bacterial meningitis. We
      evaluated the effect of alpha-MSH in a rat model of pneumococcal meningitis. Rats
      were intracisternally infected with Streptococcus pneumoniae and treatment was
      started 6 h after infection. Both systemic and intracisternal alpha-MSH failed to
      influence blood-brain barrier disruption, increased intracranial pressure, brain
      cytokine concentrations (IL-1beta, IL-6, TNF-alpha, MIP-2, and IL-10), CSF
      bacterial titers, and clinical parameters of disease severity (weight loss, body
      temperature, and blood pressure), although the treatment strongly increased the
      CNS concentrations of alpha-MSH. However, systemic but not intracisternal alpha
      MSH slightly reduced the CNS leukocyte accumulation, indicating that leukocyte
      extravasation is inhibited by alpha-MSH from the blood side. Our results show
      that alpha-MSH reduces the CNS leukocyte accumulation by its systemic action, but
      does not attenuate meningitis-associated intracranial complications.

PMID- 11311331
TI  - Endothelin-1 and monocyte chemoattractant protein-1 modulation in ischemia and
      human brain-derived endothelial cell cultures.
AB  - Brain tissue damage due to ischemia/reperfusion has been shown to be caused, in
      part, by activated macrophages infiltrating into the post-ischemic brain. Using
      the Middle Cerebral Artery Occlusion (MCAO) mouse model, this study demonstrated
      that, in vivo, both endothelin-1 (Et-1), a potent vasoconstrictor, and the
      macrophage chemokine, monocyte chemoattractant factor-1 (MCP-1) are induced in
      ischemia. Further studies, using human brain-derived endothelial cells (CNS-EC),
      showed that in vitro, Et-1 can directly stimulate MCP-1 mRNA expression and MCP-1
      protein; and this Et-1-induced MCP-1 production is mediated by the ET(A)
      receptor. Inflammatory cytokines, tumor necrosis factor alpha and interleukin
      1beta, functioned additively and synergistically, respectively, with Et-1 to
      increase this MCP-1 production. Partial elucidation of the signal transduction
      pathways involved in Et-1-induced MCP-1 production demonstrated that protein
      kinase C-, but not cAMP-dependent pathways are involved. These data demonstrate
      that Et-1, functioning as an inflammatory peptide, increased levels of MCP-1,
      suggesting a mechanism for chemokine regulation during ischemia/reperfusion
      injury.

PMID- 11311332
TI  - Schwann cell-specific regulation of IL-1 and IL-1Ra during EAN: possible
      relevance for immune regulation at paranodal regions.
AB  - We reported Schwann cell (SC)-specific autoregulation of IL-1 in vitro [J.
      Neuroimmunol. 74 (1997a)]. Whether SC resume this autoregulatory potential in
      vivo and what significance it may have for processes leading to inflammation and
      demyelination of the peripheral nerve remain obscure. Therefore, we examine SC
      specific autoregulation of IL-1alpha, IL-1beta and their natural antagonist IL-1
      receptor antagonist (IL-1Ra) during experimental autoimmune neuritis (EAN), a
      model for the human Guillain-Barre syndrome. Autoregulation of IL-1 by SC was
      analyzed in both, actively induced and adoptively transferred, EAN. Sciatic
      nerves were sampled before the onset of clinical signs, 2 to 11 days post
      immunization (dpi), with P2 peptide, and during clinically manifest disease, 11
      to 15 dpi. In adoptively transferred EAN, sciatic nerves were analyzed at
      preclinical stage, 2 to 4 days post P2 peptide-specific cell transfer (dpt) and
      during clinical manifested phase, 5 to 10 dpt. In both models, IL-1alpha and IL
      1beta were expressed by SC, during preclinical EAN. IL-1Ra was not detectable in
      SC at preclinical stage. Further development and progression to clinically
      manifest disease was accompanied by SC-specific expression of IL-1Ra. Although
      present in other cells in the nerve, IL-1alpha and IL-1beta were hardly
      detectable in SC during clinical EAN. IL-1Ra immunoreactivity highly co-localized
      with myelin associated glycoprotein (MAG), one of the markers for paranodal
      regions, sites essential for proper impulse transmission. Paranodes are also
      primary sites where activated macrophages make contact with SC, prior to
      infiltration.SC-specific autoregulation of IL-1 and IL-1Ra is suggestive of its
      relevance for immune regulation at paranodes during EAN.

PMID- 11311333
TI  - "Classic" myelin basic proteins are expressed in lymphoid tissue macrophages.
AB  - "Classic" myelin basic proteins (MBPs) are demonstrated in lymph nodes of SJL
      mice by western blot and RT-PCR. Interestingly, expression of these "classic"
      MBPs was increased during the late relapsing phase of adoptive experimental
      autoimmune encephalomyelitis (EAE). When splenocytes from SJL mice were separated
      into macrophage versus B lymphocyte-enriched populations, intact MBP isoforms
      were demonstrated in the macrophage-enriched population while undetectable in the
      B lymphocyte-enriched population. RT-PCR demonstrated "classic" MBP transcripts
      in splenic macrophages, as well as in a macrophage cell line (RAW). The
      expression of "classic" MBPs in lymphoid tissue macrophages raises the
      possibility that MBP-specific T cells may be exposed to autoantigen outside the
      central nervous system (CNS).

PMID- 11311334
TI  - Constitutive and cytokine-induced expression of MHC and intercellular adhesion
      molecule-1 (ICAM-1) on human myoblasts.
AB  - We studied the expression of MHC-I and MHC-II molecules and ICAM-1 in cultured
      human myoblasts in response to IL-1beta, IL-4, IL-6, IFN-gamma and LPS. IFN
      gamma, LPS and IL-4 greatly increase MHC-I molecule expression. MHC-II molecule
      expression is induced only by IFN-gamma. Membrane ICAM-1 and mRNA expression are
      absent under basal conditions, but can be induced by IFN-gamma, IL-1beta, IL-4,
      LPS and IL-6 with different efficiencies and time-courses. Soluble ICAM-1
      secretion can be induced to a different extent by all cytokines. Our study shows
      that the expression of adhesion-related molecules in muscle is finely regulated
      by these cytokines.

PMID- 11311335
TI  - Changes in plasma nerve growth factor levels in older adults associated with
      chronic stress.
AB  - Evidence indicates that the actions of nerve growth factor (NGF) reach beyond the
      nervous system and might modulate immune function. Based on reports that blood
      NGF rises following the acute stress of parachute jumping, we investigated
      whether exposure to a chronic stressor, caregiving for a cognitively impaired
      spouse, could alter the levels of blood NGF. High perceived stress and depression
      in caregivers (vs. well-matched controls) were associated with elevated blood
      NGF. These data suggest that exposure to this chronic stressor can alter the
      concentrations of circulating NGF, and that psychological stress can induce
      changes in NGF concentrations in older adults.

PMID- 11311336
TI  - NK cell-mediated lysis of autologous human oligodendrocytes.
AB  - Although considered an autoimmune disease, the mechanisms underlying
      oligodendrocyte (OL)/myelin injury in multiple sclerosis (MS) remain to be
      established. We utilized in vitro assays to demonstrate that human OLs, as well
      as other glial elements (astrocytes, microglia), were susceptible to injury
      mediated by peripheral blood-derived mononuclear cell preparations (MNCs)
      enriched for natural killer (NK cells) by depleting CD3(+) +/- CD19(+) cells
      through use of either magnetic beads or cell sorting. Cytotoxic effects of the NK
      cell-enriched effectors were dependent on pre-exposure of these cells to IL-2.
      Furthermore, we found that autologous OLs were as susceptible to injury mediated
      by IL-2 activated NK cells as were heterologous OLs. In context of the tissue
      injury that occurs in MS, our results suggest that the inflammatory milieu in MS
      lesions could provide conditions required for NK cell activation and that such
      effector cells can bypass the putative protective effects of self-MHC class I
      molecules that may be expressed on OLs.

PMID- 11311337
TI  - Sequence variation in the transforming growth factor-beta1 (TGFB1) gene and
      multiple sclerosis susceptibility.
AB  - Genome screenings in multiple sclerosis (MS) have identified multiple
      susceptibility regions supporting a polygenic model for this disease. Evidence
      for linkage was consistently observed at ch.19q13 suggesting the presence of an
      MS gene(s) in this region. Several interesting candidate genes are encoded within
      this region, including transforming growth factor-beta 1 (TGFB1) and interleukin
      11 (IL11). Both are multifunctional cytokines with significant and well
      characterized immunomodulatory properties. We performed a comprehensive
      evaluation of common polymorphisms within the TGFB1 and IL11 loci and three
      closely flanking microsatellite markers (D19S421, CEA, D19S908) in 161
      stringently ascertained and clinically characterized MS multiplex families using
      tests of both linkage (lod score, sib-pair analysis) and association (pedigree
      disequilibrium test or PDT). Patients and families were stratified by HLA-DR2
      status to search for two-locus interactions. Suggestive evidence for linkage and
      association to CEA (lod score = 1.25, theta = 0.20, p = 0.015, respectively),
      located 0.4 cM from TGFB1, was observed in DR2 positive families only. Distinct
      clinical phenotypes were also examined and an association between a TGFB1
      haplotype and a mild disease course was present (p = 0.008), raising the
      possibility that TGFB1 or a nearby locus may influence disease expression.

PMID- 11311338
TI  - Quantitative assay for group M (subtype A-H) and group O HIV-1 RNA detection in
      plasma.
AB  - A quantitative HIV-1 test is described based on a competitive RT-PCR assay
      combined with a sandwich hybridization as a detection system. The internal RNA
      standard (IS) was designed specifically to be competitive during the
      amplification and during the hybridization step. Sample viral load determination
      was carried out with one RT-PCR in the presence of 10(3) IS copies. The HIV-1
      copy number was calculated by reference to an external standard curve performed
      on known and increasing amounts of the reference HIV-1 (Ref HIV-1) RNA co
      amplified with a constant amount of the IS RNA. The assay had a linear range from
      10(1) to 10(6) HIV-1 copies. HIV-1 strains belonging to the different subtypes
      from group M, but also group O, were all detected. Absolute quantification of
      purified HIV-1 RNA copies gave identical results as the AMPLICOR HIV-1 Monitor
      assay. The quantification of patient's samples was evaluated according to
      different criteria such as dynamic range, sensitivity, efficacy of material
      recovery, reproducibility and convenience of sample handling. The microplate
      format of the assay combined with the colorimetric detection provides a
      convenient tool and fulfills the requirement for routine molecular diagnostic
      laboratories.

PMID- 11311339
TI  - Early detection of cacao swollen shoot virus using the polymerase chain reaction.
AB  - A polymerase chain reaction assay was developed which allows early detection of
      cacao swollen shoot virus (CSSV) in DNA extracts from cacao plantlets
      agroinoculated with the Togolese isolate Agou 1. The primers used were derived
      from badnavirus conserved sequences and nucleic acid was extracted with the Plant
      DNeasy extraction kit (Qiagen). CSSV genome was detectable between 6 and 20 days
      after inoculation. The first leaf symptoms appeared after 4 weeks and the first
      shoot swelling symptoms after 8 weeks.

PMID- 11311340
TI  - Detection of Epstein--Barr virus-determined nuclear antigen-2 mRNA by in situ
      hybridization.
AB  - A mRNA in situ hybridization method was developed to detect mRNA of Epstein--Barr
      virus-determined nuclear antigen-2 (EBNA2). Strong in situ hybridization signals
      were detected in EBNA2-transfected cells with the antisense probe but not with
      the sense probe of this mRNA. Hybridization signals were also found in formalin
      fixed paraffin-embedded tissue samples from patients with invasive uterine
      cervical cancer and with cervical intraepithelial neoplasia. The sensitivity of
      mRNA in situ hybridization was higher than that of Northern blotting, and almost
      the same as that of immunofluorescence staining using monoclonal anti-EBNA2
      antibody. It is concluded that this method is useful for sensitive and convenient
      detection of EBNA2.

PMID- 11311341
TI  - Quantitation of HIV-1 by real-time PCR with a unique fluorogenic probe.
AB  - Quantitation of HIV-1 specific RNA and DNA is pivotal to understanding the
      pathophysiology of HIV-1 diseases. A method has been developed for quantitation
      of HIV-1 DNA/RNA by real-time PCR using a unique fluorogenic primer-probe adduct
      known as scorpion. The probe hybridises to the extension of the adjoining primer
      intramolecularly, a process kinetically and thermodynamically more favourable
      than the conventional bimolecular probe-target hybridisation. Data presented in
      this paper indicate that the scorpion assay is extremely robust and is quite
      comparable to beacon-based assays. The scorpion assay is also comparable to
      quantitative competitive PCR (QC--PCR) assays but requires only a fraction of
      time and effort. Additionally, the dynamic range of the scorpion assay is several
      log-fold higher than the conventional end point PCR assays. As few as ten copies
      of vDNA can be detected in the presence of a large excess of exogenously added
      genomic DNA. Limiting dilution analysis indicates that the assay is capable of
      detecting a single copy of the viral template. Thus, the scorpion assay presents
      a specific and sensitive approach for quantitation of DNA/RNA templates by real
      time PCR.

PMID- 11311342
TI  - Development of a simplified assay for the detection of neutralizing antibodies to
      Japanese encephalitis virus.
AB  - Japanese encephalitis virus is a common cause of viral encephalitis in Asia with
      an estimated 45,000 cases annually. It causes significant morbidity and
      mortality. It is transmitted primarily by Culex mosquitoes between birds and
      animals, while man is thought to be an accidental, dead-end host. Since dengue is
      also prevalent usually in Japanese encephalitis-endemic areas, all Japanese
      encephalitis positive sera must be confirmed by detecting Japanese encephalitis
      specific neutralizing antibodies. The plaque reduction neutralization test is the
      gold standard for detecting and quantifying Japanese encephalitis neutralizing
      antibodies. This test, however, takes about a week and is carried out in 6 or 24
      well plates, which limits its usage for large-scale screening. A simplified assay
      was developed for the detection and quantification of Japanese encephalitis
      neutralizing antibodies. The assay, which is carried out in 96-well plates, would
      be suitable for use in the mass screening of the population's immunity level as
      well as for use in vaccine efficacy studies.

PMID- 11311343
TI  - Construction of recombinant swinepox viruses and expression of the classical
      swine fever virus E2 protein.
AB  - To explore the swinepox virus (SPV) as a potential live vector for immunization,
      a vector was developed for the construction of a recombinant SPV carrying foreign
      genes. In this system, a foreign gene placed under the strong vaccinia virus
      promoter P(11) can be inserted into the viral thymidine kinase (TK) gene, and the
      recombinant virus can be isolated in a non-selective medium by the co-expression
      of E. coli lacZ gene. Compared with the wild type virus, the TK(-)recombinant SPV
      showed a modest level of attenuation in porcine cells while more attenuation was
      observed in monkey or human cells. Using this system, a recombinant virus
      expressing the E2 glycoprotein of classical swine fever virus (CSFV) was
      produced. Engineered with the gX signal sequence of the pseudorabies virus, and
      transmembrane domain of E2, the E2 protein was expressed as a dimeric form in the
      cytoplasm of the infected cells.

PMID- 11311344
TI  - Use of the squirrel monkey Saimiri sciureus to optimize serological tests for
      diagnosis of Bunyavirus infection in humans.
AB  - Several arthropod-borne viruses of the large Bunyaviridae virus family have been
      isolated in South America. There are few data about the incidence of these
      viruses in man, except for the Oropuche virus. Since haemagglutination inhibition
      tests are difficult to perform, only enzyme-linked immunosorbent assays (ELISAs)
      are used. Nevertheless, positive controls are necessary for ELISA, and infected
      humans are rare. Squirrel monkeys (Saimiri sciureus) were therefore infected
      experimentally to assess their value as positive controls in such assays. The
      kinetics of viraemia and of antibody responses after infection with eight
      Bunyaviruses present in the Amazonian forest were studied. No viraemia was seen
      in most cases, but, with every virus studied, immunoglobulin (Ig)M and IgG
      antibody responses were observed, beginning between days 5 and 14 after infection
      for IgM and days 14--18 after infection for IgG. This model thus provides
      reliable positive controls for ELISAs in humans. Their availability will allow
      determination of the seroprevalence of Bunyaviruses in the human population of
      French Guiana.

PMID- 11311345
TI  - Chromosomal positioning of human T-lymphotropic type 1 proviruses by fluorescence
      in situ hybridisation.
AB  - Fluorescence in situ hybridisation (FISH) was employed to identify the
      chromosomal integration site of the human T-cell lymphotropic virus, type 1 (HTLV
      1) present in T-cell clones derived from HTLV-1-infected individuals and a
      virally transformed cell line, C8166-45. Proviral sequences were detected in
      C8166-45 but not uninfected Jurkat cells. Integration sites were reliably
      detected in T-cell clones determined previously to be infected with HTLV-1. The
      results indicated that the transformed cell line and some of the T-cell clones
      possessed more than one proviral integration site. This hybridisation system is
      useful for determining the number of integration events and for localising
      proviruses to specific chromosomal regions.

PMID- 11311346
TI  - Analysis of the diversity of African streak mastreviruses using PCR-generated
      RFLPs and partial sequence data.
AB  - Maize streak virus (MSV) is the most economically significant member of a diverse
      group of African grass-infecting Mastrevirus species in the family Geminiviridae.
      We designed a single set of degenerate primers which enables the PCR
      amplification of an approximately 1300 bp DNA fragment spanning both conserved
      (the RepA gene) and variable (the long intergenic region and MP gene) portions of
      these viruses' genomes. Using restriction fragment length polymorphism (RFLP)
      analysis of PCR products obtained from 39 MSV, one SSV, and two PanSV isolates,
      it was possible to both identify the different virus species, which differ in
      nucleotide sequence by up to 40%, and to differentiate between MSV isolates
      sharing up to 99% sequence identity. The reliability of the RFLP data for typing
      the MSV isolates was verified by the phylogenetic analysis of the partial genomic
      nucleotide sequences of a representative subset of the MSV isolates. Based on
      both the RFLP and sequence data, the MSV isolates could be clearly differentiated
      into the four groups: these were a group of predominantly maize-infecting
      isolates, and three groups containing grass/wheat-infecting isolates. RFLP
      analysis also revealed a number of mixed virus infections in which, in certain
      instances, it was possible to identify individual population members.

PMID- 11311347
TI  - Evaluation of a recombinant line blot for diagnosis of Epstein-Barr Virus
      compared with ELISA, using immunofluorescence as reference method.
AB  - A commercial line blot using recombinant antigens was compared with a commercial
      ELISA and 'in-house' IFA (reference test). Two panels were evaluated: Panel A was
      selected to distinguish between primary infections (89), past infections (20) and
      seronegatives (8) in immunocompetent individuals. In panel B, patients with a
      high number of reactivations were included: immunosuppressed patients (37),
      lymphoma (19), nasopharyngeal carcinoma (10), chronic fatigue syndrome (14).
      Blood donors (43) and cross-reactive sera (29) were added as controls. Line blot
      and IFA were concordant in 94% of primary infections, 100% of seronegatives and
      100% of past infections, similar to ELISA. Results differed significantly with
      regard to reactivations. When compared with IFA, the incidence of reactivations
      was overestimated by the blot, 24 and 58% in blood donors and cross-reactive
      sera, respectively. ELISA showed a similar problems with 21 and 34% indeterminate
      results, respectively. The line blot is easy to carry out, has a good concordance
      with the reference IFA for primary infections, and is, therefore, a sufficient
      choice for distinguishing primary infection from seronegative and past infection.
      EBV reactivation assessment will require other methods such as EBV viral load.

PMID- 11311348
TI  - Purification of woodchuck hepatitis surface antigen using a monoclonal antibody
      raised against the antigen.
AB  - Woodchuck hepatitis virus (WHV) is closely related to the human hepatitis B virus
      (HBV) and infection of woodchucks with WHV creates a useful model for studies of
      immunity, pathogenesis and therapy of HBV infection. To increase the usefulness
      of this model, monoclonal antibodies were raised to woodchuck hepatitis surface
      antigen (WHsAg) and one of these antibodies was used to purify the antigen by
      affinity chromatography from serum, a simpler and quicker method of purification
      than the current ultracentrifugation methods. The bands found by SDS
      polyacrylamide gel electophoresis of WHsAg were the major 25 and 29 kilodalton
      (kDa) bands and a triplet of 45, 51 and 55 kDa which are thought to be the
      glycosylated and unglycosylated middle and large WHsAg. Both the antibody and the
      antigen are valuable reagents for the study of WHV infection.

PMID- 11311349
TI  - A rapid real-time quantitative polymerase chain reaction for hepatitis B virus.
AB  - Quantification of hepatitis B virus (HBV) DNA in serum is important for
      monitoring treatment. A rapid and cost effective alternative to the methods
      available currently was developed based on a real-time quantitative polymerase
      chain reaction (PCR) done in the LightCycler apparatus. Primers and a probe for
      sequences of the surface gene of HBV were designed and quantification achieved by
      reference to standards containing known concentrations of the target sequence. A
      single copy of the HBV genome could be detected if present in the reaction
      mixture. The quantitative range of the assay was from 4 x 10(2) to 1.3 x 10(10)
      surface gene copies/ml serum. Nested PCR was required for quantification in the
      lower part of this range (<10(5) copies). The real-time PCR and Amplicor Monitor
      (Roche) tests performed comparably at virus concentrations below 10(6) copies/ml.
      The commercial test underestimated higher concentrations of virus.

PMID- 11311350
TI  - Development of a multiplex AmpliDet RNA for the simultaneous detection of Potato
      leafroll virus and Potato virus Y in potato tubers.
AB  - A novel isothermal multiplex AmpliDet RNA system is described for the
      simultaneous amplification and detection of Potato leafroll virus (PLRV) and
      Potato virus Y (PVY) in seed potatoes. The risk of contamination by carry-over
      during diagnostic screening is eliminated by performing the reaction in a single
      closed tube. The viruses present in a sample are identified using differently
      coloured molecular beacons directed to a selected virus-specific sequence within
      the amplicon formed during amplification. With this system, as little as 10 fg of
      purified PLRV or PVY can be detected. The presence of both viruses in a sample is
      detected by the multiplex assay within a high range of virus concentrations. The
      reliability of the multiplex assay was compared with the enzyme-linked
      immunosorbent assay for detection of PLRV- or PVY-antigens in potato tubers. The
      multiplex assay detected clearly the viruses present originally in the potato
      tubers in all samples, demonstrating its potential for routine diagnostic work
      and high-throughput screening.

PMID- 11311351
TI  - Optimisation and standardisation of a method for detecting and enumerating
      bacteriophages infecting Bacteroides fragilis.
AB  - A method for the detection and enumeration of bacteriophages infecting
      Bacteroides fragilis has been standardised. The recommended host strain is
      RYC2056 (ATCC 700786) because of the relatively high counts (10(4)-10(5)
      PFU/100ml) that it recovers in sewage from very different geographical areas. The
      addition of 0.25% bile to the culture and assay media and the manipulation of the
      host strain under strict anaerobic conditions resulted in a significant increase
      (more than 100%) in the number of phages detected. No other changes in the media
      and culture conditions resulted in changes in the phage counts detected. However,
      these increases do not justify changing the culture conditions and media
      described, taking into consideration that bile renders the media cloudy making it
      difficult to follow the host growth and that most laboratories do not have the
      facilities to work under strict anaerobic conditions. Nalidixic acid (100
      microg/ml) and kanamycin (100 microg/ml) in the assay medium significantly reduce
      the background flora from polluted samples without affecting the phage counts.
      Freezing cultures just before the end of the log-phage growth at (-70+/-10)
      degrees C with BSA-sucrose as cryoprotector, storing of 1-2 ml in glass vials at
      (-70+/-10) degrees C and using them directly to inoculate fresh broth allows the
      obtention of cultures ready for phage enumeration in about 2.5 h. All these
      developments have been incorporated into a procedure that makes the method for
      detecting phages infecting B. fragilis as workable as the standardised methods
      available for the detection of coliphages.

PMID- 11311352
TI  - A system to enhance the sensitivity of digoxigenin-labelled probe: detection of
      B19 DNA in serum samples.
AB  - A highly sensitive dot-blot hybridisation assay for the routine screening of
      numerous samples is described, using parvovirus B19 as a model. Digoxigenin
      labelled B19 DNA probe was constructed by PCR, hybrids were detected by an anti
      digoxigenin monoclonal antibody followed by a second step, using anti-mouse
      antibodies conjugated to an alkaline phosphatase-dextran complex (EnVision, Dako)
      was carried out. The sensitivity of the assay was evaluated using both
      colourimetric and chemiluminescent substrates for the alkaline phosphatase and
      was compared with a dot-blot hybridisation assay using the digoxigenin-labelled
      probe and a standard detection system. With the colourimetric substrate, the
      EnVision system was able to detect 10 fg of B19 DNA, while with the
      chemiluminescent substrate the sensitivity increased by up to 2 fg (6 x 10(2)
      genome copies). This detection system was shown to increase the sensitivity of
      the assay compared to the standard colourimetric visualisation for the
      digoxigenin-labelled probe, which could detect 0.1 pg. On account of its
      sensitivity and specificity the dot-blot hybridisation assay together with the
      chemiluminescent substrate for the EnVision detection system was used to analyse
      760 serum samples; the same sera were tested for B19 DNA with the standard
      colourimetric visualisation for the digoxigenin-labelled probe used routinely in
      the diagnostic laboratory.

PMID- 11311353
TI  - Simple detection of point mutations associated with HIV-1 drug resistance.
AB  - A novel assay is described for the detection of HIV-1 drug resistance that is
      simple, cheap and sensitive. HIV-1 drug resistance in B and non-B HIV-1 subtypes
      was investigated using Mutagenically-Separated PCR (MS--PCR) --- a competitive
      semi-nested PCR which uses mutagenic primers. The assay was assessed for
      sensitivity, specificity and its ability to detect mutant virus within a mixed
      mutant--wild-type population. Gene sequencing was carried out simultaneously for
      comparison. MS--PCR detected five copies of HIV-1 RNA from laboratory isolates
      and 50 copies from patient samples. We demonstrate 100% specificity of detection
      for wild type or mutant virus for clades A, B, C, D and E. For mixed populations
      of virus, MS--PCR can detect at least a 10% mix of wild type:mutant, or vice
      versa. When applied to African patient samples MS--PCR detected 91.6% of the
      codons tested. Concordance with sequencing data was 88.8% for protease and 97.2%
      for RT. MS--PCR is sensitive and specific for the detection of mutations in HIV
      1, and can be adapted easily to test for resistance at any codon of interest.

PMID- 11311355
TI  - Comparison of bioassays and laboratory assays for apple stem grooving virus.
AB  - The standard field double-budding assay with the indicator Virginia Crab and the
      glasshouse test with the indicator Malus micromalus, were compared with ELISA and
      immunocapture PCR for the detection of Apple stem grooving virus (ASGV) in 102
      apple trees and three oriental pear. Twenty-two trees were positive for ASGV by
      both ELISA and IC-PCR but three of these trees were negative by Virginia Crab,
      three were negative by M. micromalus and one was negative by both these
      bioassays. The infected trees were re-tested by IC-PCR and ELISA in a second
      year; the IC-PCR results were confirmed but two of the 22 infected trees were
      negative by ELISA. On this evidence, IC-PCR is a more reliable assay for ASGV
      than the slow and expensive bioassays.

PMID- 11311354
TI  - Development and evaluation of an antibody capture ELISA for detection of IgG to
      Epstein-Barr virus in oral fluid samples.
AB  - The development of an EBV IgG antibody capture ELISA (GACELISA) for detection of
      EBV viral capsid antigen specific IgG in oral fluids is described. The assay was
      optimised and evaluated using paired serum and oral fluid samples from healthy
      laboratory staff (n=82) and oral fluids collected either for routine measles,
      mumps, and rubella testing (n=629) or for an epidemiological study of atopic
      dermatitis (n=252). Statistical analysis by mixture modelling was used to
      determine the GACELISA cut-off and to estimate the sensitivity and specificity of
      the assay. Sensitivity and specificity was also assessed by comparing the results
      of immunofluorescence assay for EBV specific IgG in serum with those of GACELISA
      in 82 matching oral fluids. Compared to serum immunofluorescence assay, oral
      fluid GACELISA was found to have a sensitivity of 82.2 and 88.9% specificity with
      these samples. Mixture modelling, predicted the GACELISA to be 88.4% sensitive
      and of 99.4% specific. The prevalence of antibody to EBV in oral fluids was found
      to be 73.8% in laboratory staff, 34.4--73.9% in measles, mumps, and rubella
      patients and 22.2% in atopic dermatitis study participants. A robust, reliable
      and reproducible EBV GACELISA has been developed which will be a useful tool for
      epidemiological investigations.

PMID- 11311356
TI  - Digital imaging microscopy of firefly luciferase activity to directly monitor
      differences in cell transduction efficiencies between AdCMVLuc and Ad5LucRGD
      vectors having different cell binding properties.
AB  - The luciferase reporter gene incorporated into adenoviral vectors is very useful
      for monitoring viral transduction of different cell types or for comparing the
      transduction efficiency of different viral constructs of one cell type.
      Luciferase protein expression can be detected and quantified with very high
      sensitivity from whole cells or organ extracts. However, its disadvantages become
      obvious when aiming at evaluation of transduction events at the single cell
      level. The results obtained from whole cell extracts cannot be directly
      correlated to single cell events. In this paper direct cellular luciferase
      imaging using cell permeable luciferin substrates is applied for comparative
      analysis of cellular transduction events by two adenoviral vectors with different
      cell binding properties. Using digital imaging microscopy we show a more than ten
      fold increase in transduction efficiency by Ad5LucRGD vectors versus AdCMVLuc
      vectors on human A549 cells.

PMID- 11311357
TI  - Rapid determination of adenoviral vector titers by quantitative real-time PCR.
AB  - Replication defective adenoviruses have been used as vectors in a variety of
      settings including gene transfer, gene manipulation, and functionality studies. A
      quantitative real-time PCR-based assay is described for rapid determination of
      physical titers of recombinant adenovirus vectors. This method is based on
      amplification of a 77 bp fragment located near the left end of the adenovirus
      type 5 genome. Evaluation of this method demonstrated that it is simple,
      sensitive and reproducible, and has a dynamic range of quantitation over 5 logs.
      This assay is applicable to purified adenovirus as well as vectors prepared by
      simple cell lysis procedure, requiring only a small amount of starting material.
      The simplicity and short turn-around time of this assay should facilitate rapid
      titer determination for a large collection of adenoviral vectors.

PMID- 11311358
TI  - Evaluation of four HIV antigen tests.
AB  - A direct comparison of different HIV antigen assays is very helpful in making an
      informed choice, not only for the testing laboratories but also for healthcare
      workers in the developing world who are looking for reliable and inexpensive
      tests/methods in the follow-up of their treated patients. As a follow-up to the
      study published previously [Fransen K., Martens G., Stynen D., Goris A., Nys P.,
      Nkengasong J., Heyndrickx L., Janssens W., van der Groen G., 1997. J. Med. Virol.
      53, 31--35] where only two tests have been compared, four different commercial
      methods for HIV antigen determination in plasma and supernatant of cell cultures
      have now been evaluated on a limited sample size (88): COULTER HIV-1 p24 Antigen
      Assay (Coulter), (Test 1) INNOTEST HIV Antigen mAb (Innogenetics) (Test 2),
      Genetic Systems HIV-1 Ag EIA (Sanofi-Pasteur(1)) (Test 3) and VIDAS HIV P24 II
      (bioMerieux) (Test 4). Of the four tests used in this study, Test 2 was by far
      the most sensitive test. In a population of 88 follow-up samples from 35
      different patients representing all stages of infection, the test detected
      confirmed p24 antigen at least once in 85.7% (30/35) of these patients, versus
      Test 3 in 74.3% (26/35), Test 4 in 71.4% (25/35), and Test 1 in 48.6% (17/35) of
      the patients. Test 2 detected confirmed p24 antigen in 84.9% of the follow-up
      samples, followed by Test 4 (65.9%), Test 3 (64.8%) and Test 1 (39.8%). Finally,
      Test 2 also proved best for detecting genetically diverse isolates.

PMID- 11311359
TI  - Parkinson's disease, pesticides and mitochondrial dysfunction.
AB  - Selective nigral degeneration with inclusion formation provoked by systemic
      administration of the herbicide rotenone, through inhibition of complex I, raises
      the question of pesticide exposure and environmental factors in general, as a
      cause of Parkinson's disease (PD). Toxin-induced complex I inhibition probably
      represents one of many potential causes of PD, but it alerts us to the dangers of
      such substances in the environment and the need to identify genetically
      susceptible populations. When vulnerable individuals become known, perhaps they
      should stay out of the garden.

PMID- 11311361
TI  - The uncommon retina of the common house mouse.
AB  - Unlike most mammals, most cones in house mouse retina express two opsins, one
      sensitive to UV-light, and another sensitive to middle-wavelengths. Is the mouse
      unique, having a single cone type that normally expresses two opsins? Or is the
      mouse a typical mammal having two cone types, but a species wide mutation results
      in co-expression of two opsins?

PMID- 11311363
TI  - Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural
      development.
AB  - We have modified an FLP/FRT-based genetic mosaic system to label either neurons
      derived from a common progenitor or isolated single neurons, in the Drosophila
      CNS. These uniquely labeled neurons can also be made homozygous for a mutation of
      interest within an otherwise phenotypically wild-type brain. Using this new
      mosaic system, not only can normal brain development be described with
      unprecedented single cell resolution, but also the underlying molecular
      mechanisms can be investigated by identifying genes that are required for these
      developmental processes.

PMID- 11311364
TI  - Fighting Bax: towards a Parkinson's disease therapy.

PMID- 11311365
TI  - Neuronal death and GSK-3beta: a tau fetish?

PMID- 11311366
TI  - MAPing the path from neuronal activity to spine motility.

PMID- 11311367
TI  - Scientific expertise in law.

PMID- 11311368
TI  - AD gene accelerates MS.

PMID- 11311369
TI  - New LTP molecule.

PMID- 11311370
TI  - Proteome efforts to follow Genome reports.

PMID- 11311371
TI  - Odor detection in zebrafish.

PMID- 11311372
TI  - The amused brain.

PMID- 11311373
TI  - New tools to look at NO.

PMID- 11311374
TI  - European research funding advances.

PMID- 11311375
TI  - US budget proposal favors biomedical over basic sciences.

PMID- 11311376
TI  - Attention mediated by synchrony of neurons.

PMID- 11311377
TI  - Proteomics of the nervous system.
AB  - The recent success of large-scale industrialized genomic sequencing opens new
      doors in studies of biological systems. In the current post-genomic era we must
      ask how to translate this DNA sequence information into an understanding of
      living cells, tissues and organisms. One of the major goals is to characterize
      protein function, biochemical pathways and networks. Achieving this aim is
      greatly advanced by application of new proteomic tools combined with database
      mining. Neuroscience in particular is poised to benefit from these approaches in
      light of its high complexity and cross-talk between different neurotransmitter
      receptors within the same synapse or across the synaptic cleft. Little is known
      about the global in vivo protein interactions within synapses, and the knowledge
      of all proteins present in such structures will help in determining sub-complexes
      and the modular arrangement of proteins within them. This article reviews the
      impact of and outlines the application of proteomic analysis in the field of
      neuroscience, illustrating this with the example of NMDA receptor complexes.

PMID- 11311378
TI  - Cortical spreading depression and migraine: new insights from imaging?
AB  - The possibility that spreading depression (SD) of cortical activity, a phenomenon
      observed in all vertebrates, causes the aura of migraine remains an open question
      in spite of nearly half a century of investigation. SD is also thought to be
      associated with the progressive neuronal injury observed during cerebral
      ischaemia. Thus, the ability to detect and investigate SD in humans might prove
      clinically significant. Animal studies of cortical spreading depression (CSD)
      have benefited greatly from the advent of relatively non-invasive imaging
      techniques. The use of these new imaging techniques for clinical studies will
      accelerate progress in this area of neurobiology.

PMID- 11311379
TI  - The endoplasmic reticulum: one continuous or several separate Ca(2+) stores?
AB  - The Ca2+ store and sink in the endoplasmic reticulum (ER) is important for Ca2+
      signal integration and for conveyance of information in spatial and temporal
      domains. Textbooks regard the ER as one continuous network, but biochemical and
      biophysical studies revealed apparently discrete ER Ca2+ stores. Recent direct
      studies of ER lumenal Ca2+ movements show that this organelle system is one
      continuous Ca2+ store, which can function as a Ca2+ tunnel. The concept of a
      fully connected ER network is entirely compatible with evidence indicating that
      the distribution of Ca2+ -release channels in the ER membrane is discontinuous
      with clustering in certain localities.

PMID- 11311380
TI  - Advances in the molecular understanding of GABA(B) receptors.
AB  - The molecular nature of the metabotropic GABA(B) receptor was for some time a
      mystery, however it was recently discovered that two related G-protein-coupled
      receptors have to heterodimerize to form the functional GABA(B) receptor at the
      cell surface. This review discusses the most recent findings in the rapidly
      expanding field of GABA(B) receptor research, and includes a summary of all
      splice variants of both receptor subunits identified to date. It also evaluates
      emerging evidence that certain splice variants might play a role in determining
      pharmacologically distinguishable receptors, and reviews receptor localization at
      the sub-cellular level and involvement in neuronal development.

PMID- 11311381
TI  - "Primitive intelligence" in the auditory cortex.
AB  - The everyday auditory environment consists of multiple simultaneously active
      sources with overlapping temporal and spectral acoustic properties. Despite the
      seemingly chaotic composite signal impinging on our ears, the resulting
      perception is of an orderly "auditory scene" that is organized according to
      sources and auditory events, allowing us to select messages easily, recognize
      familiar sound patterns, and distinguish deviant or novel ones. Recent data
      suggest that these perceptual achievements are mainly based on processes of a
      cognitive nature ("sensory intelligence") in the auditory cortex. Even higher
      cognitive processes than previously thought, such as those that organize the
      auditory input, extract the common invariant patterns shared by a number of
      acoustically varying sounds, or anticipate the auditory events of the immediate
      future, occur at the level of sensory cortex (even when attention is not directed
      towards the sensory input).

PMID- 11311382
TI  - The anatomical and computational basis of the rat head-direction cell signal.
AB  - As a rat navigates through space, neurons called head-direction (HD) cells
      provide a signal of the rat's momentary directional heading. Although partly
      guided by landmarks, the cells also show a remarkable ability to track
      directional heading based on angular head movement. Theoretical models suggest
      that the HD cells are linked together to form an attractor network, and that
      cells which signal angular velocity update the directional setting of the
      attractor. Recently, cell types similar to those required theoretically have been
      discovered in the lateral mammillary and dorsal tegmental nuclei. Lesion and
      anatomical data suggest these nuclei might constitute the postulated attractor
      path integration mechanism, and that they provide the HD cell signal to cortical
      areas where it has been observed.

PMID- 11311383
TI  - Neural correlates of attention in primate visual cortex.
AB  - The processing of visual information combines bottom-up sensory aspects with top
      down influences, most notably attentional processes. Attentional influences have
      now been demonstrated throughout visual cortex, and their influence on the
      processing of visual information is profound. Neuronal responses to attended
      locations or stimulus features are enhanced, whereas those from unattended
      locations or features are suppressed. This influence of attention increases as
      one ascends the hierarchy of visual areas in primate cortex, ultimately resulting
      in a neural representation of the visual world that is dominated by the
      behavioral relevance of the information, rather than designed to provide an
      accurate and complete description of it. This realization has led to a rethinking
      of the role of areas that have previously been considered to be "purely sensory".

PMID- 11311385
TI  - Alterations of physiological energetics, growth and reproduction of Daphnia magna
      under toxicant stress.
AB  - The study investigates the relationship between changes in physiological
      energetics of organisms and alterations of growth, development and reproduction
      of Daphnia magna. Groups of primiparous daphnids were subjected to 8-day
      exposures to the heavy metals cadmium and copper or to the cationic surfactant,
      cetyltrimethylammonium bromide (CTAB). Energetic alterations were estimated from
      the measurement of oxygen consumption and feeding activity which was performed
      during the last 3 days of the exposure period and from the calculation of
      simplified carbon balances. The physiological effects were compared to effects on
      organismal growth and reproduction as obtained from 17-day exposure experiments.
      Toxicant exposure reduced weight and body length of daphnids indicating an
      impaired growth rate, but effects on total metabolic costs measured as weight
      specific oxygen consumption could not be detected. Net carbon gain of individuals
      decreased in a concentration-dependent way for the tested chemicals reflecting
      effects on biomass of daphnids. In the case of cadmium and copper, reproduction (
      summation operatormx: number of offspring per female of age x born during the
      time interval x-1 to x, summarised over the entire exposure period) and the
      estimate for the intrinsic rate of natural increase, derived from the 17-day
      exposure-experiment, were affected at concentrations comparable to the effect
      levels as observed for growth. In the case of copper, the concentrations
      affecting growth and reproduction were close to the 17-day LC(50) value. CTAB
      caused a reduction in body length of primiparous daphnids whereas a decrease in
      the reproductive performance was not apparent. In conclusion, the chemicals did
      not change metabolic costs of exposed daphnids as it would be expected as a
      consequence of resistance or repair mechanisms, however, they induced alterations
      of SFG, growth, reproduction and intrinsic rate of natural increase. These
      alterations were chemical-specific. The fact that toxicant-related effects on
      growth and reproduction could not be linked to an elevated metabolic rate of
      daphnids may indicate that demand side effects occurred early during exposure -
      before the start of respirometric measurements - or that effects on growth were
      caused by an altered energy uptake. The results illustrate the importance of
      trade-off processes in regulating the distribution of energy among growth and
      reproduction of daphnids.

PMID- 11311386
TI  - Metallothionein and cortisol receptor expression in gills of Atlantic salmon,
      Salmo salar, exposed to dietary cadmium.
AB  - Commercial fish feeds may contain significant levels of cadmium (Cd). However,
      little is known about the effects of dietary cadmium on fish organs, especially
      gills, the key osmoregulatory organ. We therefore studied the effects of dietary
      cadmium on metallothionein (MT) and cortisol receptor (GR) immunoreactivity in
      the branchial epithelium of the Atlantic salmon (Salmo salar). Cadmium was daily
      administered via food at 0.2mg (control), 5mg (low dose) and 125 mg (high dose)
      Cd per kilogram dry pellet weight. Fish were sampled after four and eight weeks.
      After both four and eight weeks, plasma cadmium concentration had increased
      significantly only in fish fed the high cadmium dose. Plasma calcium, sodium,
      chloride and cortisol levels were not affected. In the controls, most MT was
      colocated with the chloride cell marker, Na(+)/K(+)-ATPase, but some MT was
      present in pavement and respiratory cells. GR expression was found in chloride,
      pavement, respiratory and undifferentiated cells in all fish groups, but cadmium
      accumulation and a marked stimulation of MT expression were seen only in the
      chloride cells in the gills of fish fed the high cadmium dose. Cadmium treatment
      did not alter GR expression. When the double staining technique for MT and GR was
      applied, a marked heterogeneity became apparent in the chloride, pavement and
      respiratory cells of both groups of cadmium-treated fish and in the control fish.
      Some fish showed double staining, others stained only for one of the antibodies,
      whereas other cells were negative for both. We conclude that cadmium entering the
      gut also enters the gills, where it accumulates in chloride cells and stimulates
      MT expression.

PMID- 11311387
TI  - Effects of endocrine modulating substances on reproduction in the hermaphroditic
      snail Lymnaea stagnalis L.
AB  - Various man-made agents like pesticides, industrial chemicals and some natural
      substances have the potential to alter hormonal pathways that regulate
      reproductive processes in certain species of wildlife. Until now, only a few
      investigations have been undertaken to determine the effects of these substances
      on reproductive capacities (fecundity and fertility) in exposed invertebrate
      aquatic species. In this study one of the most abundant mollusc of European
      limnic systems, the hermaphroditic gastropod Lymnaea stagnalis was investigated
      to determine the effects of endocrine modulating substances on reproductive
      parameters. Known endocrine modulating substances were tested using the following
      nominal concentrations; Tributyltin (TBT in ng Sn/l) and beta-sitosterol at 1, 10
      and 100 ng/l, respectively, and 4-nonylphenol (4-NP) at 1, 10 and 100 microg/l.
      In addition, experiments were carried out with 1, 10 and 100 ng/l of t
      methyltestosterone. All the testing was carried out on recently matured adults of
      Lymnaea. Fifteen to twenty snails per treatment were exposed for between 7 and 12
      weeks in a semi-static test with a weekly exchange of testwater. Shell height and
      weight and mortality of the adults, egg production, hatching rate of the eggs,
      and histopathology of the adult snails were analysed. The same parameters were
      investigated on F(1) generation snails from exposed parents at two dates (1 week
      after exposure and at the end of the exposure duration). Treatments with TBT and
      4-NP had only slight effects on the egg production of the adults and hatching
      rate of the eggs. However, increased histopathological changes were observed in
      epithelial tissues of the adult snails, e.g. lung and foot also characterised by
      extreme inflammatory processes. While beta-sitosterol and t-methyltestosterone
      had no effect on the shell height and weight or the mortality of adult snails nor
      on the egg production or ensuing egg hatching rate, beta-sitosterol treated
      snails presented a distinct atrophy of the albumen gland and so did t
      methyltestosterone, albeit with a lower degree of atrophy. The observed
      histopathological effects due to exposure to tributyltin or 4-NP are suggested to
      lead to long-term adverse reproductive effects mediated by an impairment of the
      fitness of the snails. In the experiments the steroid-dependant (beta-sitosterol
      and t-methyltestosterone) degeneration of the albumen gland caused no obvious
      adverse effects on the fecundity nor fertility of the adults or on F(1)
      generation. However, the impact on fertility following a prolonged exposure to
      high concentrations of the phytoestrogen cannot be predicted.

PMID- 11311388
TI  - Organotins in zebra mussels (Dreissena polymorpha) and sediments of the Quebec
      City Harbour area of the St. Lawrence River.
AB  - Toxic antifouling agents such as tributyltin (TBT) and triphenyltin (TPT) have
      been released in aquatic ecosystems through the use of antifouling paint applied
      to ship hulls, pleasure crafts and fish nets and these compounds can
      bioaccumulate in aquatic organisms. The purpose of this study was 1) to assess
      the extent of the distribution of organotins from a contaminated marina to the
      St. Lawrence River system by measuring organotin concentrations in zebra mussels
      (Dreissena polymorpha) and in sediments collected from 9 sites along the St.
      Lawrence River near Quebec City in July 1998, and 2) to examine the
      histopathological condition of zebra mussel tissues from these sites. TBT
      concentrations in zebra mussels were between 37 and 1078 ng Sn g(-1) wet weight,
      with the highest value found in the Bassin Louise marina. Elevated concentrations
      were also found in two other marinas. The concentrations decreased sharply to
      background levels just outside the marinas. All butyltins were detected in all
      sediments analysed, with highest values found in the Bassin Louise marina.
      Phenyltins were detected in three of the nine sites in low concentrations (<55 ng
      Sn g(-1)) in zebra mussels. There was a significant correlation between TBT in
      sediments and mussels. Gonadal development of zebra mussels varied largely
      between sites, and was negatively associated to TBT levels in mussel tissue. This
      study shows that TBT contamination remains a problem in localised freshwater
      sectors of the St. Lawrence River.

PMID- 11311389
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and cytochrome
      P4501A expression in developing Fundulus heteroclitus embryos.
AB  - Fundulus heteroclitus embryos were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) during early development using nanoinjection or water bath exposure. TCDD
      caused developmental abnormalities that included hemorrhaging, loss of vascular
      integrity, edema, stunted development and death. The LC(50) and LD(50) of TCDD
      for Fundulus embryos were approximately 19.7+/-9.5 pg TCDD/microl (water bath)
      and 0.25+/-0.09 ng TCDD/g embryo (nanoinjection). To identify a possible cause
      for these developmental abnormalities we analyzed the effects of TCDD on
      apoptotic cell death and cytochrome P4501A (CYP1A) expression in the embryos.
      TCDD exposure increased apoptotic cell death in several tissues including brain,
      eye, gill, kidney, tail, intestine, heart, and vascular tissue. CYP1A expression
      was also increased in the TCDD-exposed embryos predominantly in liver, kidney,
      gill, heart, intestine, and in vascular tissues throughout the embryo. There was
      co-occurrence of TCDD-induced apoptosis and CYP1A expression in some, but not
      all, cell types. In addition the dose response relationships for apoptosis and
      mortality were similar, while CYP1A expression appeared more sensitive to TCDD
      induction.

PMID- 11311390
TI  - Male goldfish reproductive behaviour and physiology are severely affected by
      exogenous exposure to 17beta-estradiol.
AB  - Mature male goldfish were exposed to different concentrations of the natural
      hormone 17beta-estradiol (E2). Two methods of exposure were employed, via
      ingestion at 0, 1, 10 and 100 microg/g food and via the water at 0, 1 and 10
      microg/l. The fish were exposed for 24-28 days during the spawning period. The
      males were then paired with an artificially induced, spawning female and their
      sexual behaviour was observed during a 15 min period. The physiological status of
      the fish was also examined with respect to GSI, presence of milt and spawning
      tubercles and the blood plasma concentration of E2. Despite the relatively short
      exposure period, exposure to physiological levels of E2 was shown to severely
      affect the male goldfish reproductive behaviour and physiology. In conclusion,
      the results from this study and the ability to interpret the effects on this well
      studied species, show that the effects of E2, and possibly other estrogenic EDCs,
      have severe effects at several vital levels of male goldfish reproduction. The
      results also suggests that the hormone E2 can act as an endocrine disrupting
      chemical (EDC) in the environment.

PMID- 11311391
TI  - Recovery of Cryptosporidium oocysts and Giardia cysts from source water
      concentrates using immunomagnetic separation.
AB  - Immunomagnetic separation (IMS) procedures for the simultaneous isolation of
      Cryptosporidium oocysts and Giardia cysts have recently become available. We
      validated Dynal's GC-Combo IMS kit using source water at three turbidity levels
      (5000, 500 and 50 nephelometric turbidity units [ntu]) obtained from different
      geographical locations and spiked with approximately 9--11 (oo)cysts per ml. Mean
      recoveries of Cryptosporidium oocysts and Giardia cysts in deionized water were
      62% and 69%, respectively. In turbid water matrices, mean recoveries of
      Cryptosporidium oocysts were between 55.9% and 83.1% while mean recoveries of
      cysts were between 61.1% and 89.6%. Marginally higher recoveries of the heat
      inactivated (oo)cysts were observed (119.4% Cryptosporidium oocysts and 90.9%
      Giardia cysts) in deionized water when compared with recoveries of viable
      (oo)cysts (69.7% Cryptosporidium oocysts and 79% Giardia cysts). Age of (oo)cysts
      on recoveries using the GC-Combo IMS kit demonstrated no effects up to 20 months
      old. Recovery of Giardia cysts was consistent for isolates aged up to 8 months
      (81.4%), however, a significant reduction in recoveries was noted at 20 months
      age. Recoveries of low levels (5 and 10 (oo)cysts) of Cryptosporidium oocysts and
      Giardia cysts in deionized water using IMS ranged from 51.3% to 78% and from
      47.6% to 90.0%, respectively. Results of this study indicate that Dynal's GC
      Combo IMS kit is an efficient technique to separate Cryptosporidium/Giardia from
      turbid matrices and yields consistent, reproducible recoveries. The use of fresh
      (recently voided and purified) (oo)cysts, aged (oo)cysts, viable and heat
      inactivated (oo)cysts indicated that these parameters do not influence IMS
      performance.

PMID- 11311392
TI  - An advanced molecular strategy to identify bacterial communities on art objects.
AB  - The application of culture-independent techniques based on molecular biological
      methods, especially on the PCR amplification of 16S rRNA genes, attempts to
      overcome some shortcomings of conventional cultivation methods and reveals far
      more complex bacterial communities on art objects than can be shown by
      cultivation methods. One of the major challenges of investigating microbial
      growth on art objects by molecular means is the extraction of DNA, due to small
      sample amounts and PCR inhibitors. In the present study, we introduce a DNA
      extraction protocol, which allowed the extraction of PCR-amplifiable DNA from
      samples derived from lime wall paintings and loamy soil underground. The DNA
      extracts were used to amplify 16S ribosomal fragments, which were subsequently
      analyzed by denaturing gradient gel electrophoresis (DGGE). In parallel with the
      DGGE analysis, clone libraries containing PCR fragments of the ribosomal gene
      were constructed and clones were screened by DGGE. Clone libraries allow the
      inclusion of the entire 16S rDNA sequence in the phylogenetic analyses of
      microorganisms, providing a more reliable phylogenetic identification of
      microorganisms than is obtained from sequence analyses of excised and directly
      sequenced DGGE bands.

PMID- 11311393
TI  - Detection of Helicobacter pylori DNA in human feces by PCR: DNA stability and
      removal of inhibitors.
AB  - In this study, the stability of Helicobacter pylori DNA in human feces and the
      effect of a diet lacking in plant material, the suspected source of PCR
      inhibitors in human feces, were investigated. In addition, a method to remove
      these inhibitors was developed. Stools inoculated with H. pylori were used as a
      model. For this purpose, a H. pylori suspension (10(8) CFU/ml) was used to spike
      stool samples obtained from four healthy adults known to be H. pylori negative.
      The evaluation of the stability of H. pylori DNA in feces showed that DNA was
      degraded after 3 days of contact with fecal material at 37 degrees C. A 2-day
      diet completely free of plant material was sufficient to eliminate PCR inhibitors
      from human feces. However, inhibitors were detected 48 h after a normal diet was
      resumed. A new technique consisting of agarose blocks containing embedded DNA as
      a template for PCR amplification was used for removal of inhibitors, following
      DNA extraction by a modified QIAamp tissue method (Qiagen, Hilden, Germany). When
      this method was applied to inhibiting stool samples known to have an inhibitory
      effect and spiked with H. pylori (5.10(8) CFU/g), a positive PCR was obtained
      showing that inhibitors present in the original DNA samples were completely
      removed. The agarose embedded DNA block method is highly efficient and provides
      clean, high quality template DNA for PCR purposes avoiding long and fastidious
      conventional extraction methods. In conclusion, this study confirms that H.
      pylori DNA degrades with time in stools. A diet free of plant material or a
      special DNA preparation can be used to remove inhibitors and to allow the
      detection of H. pylori.

PMID- 11311394
TI  - Effects of cell surface damage on surface properties and adhesion of Pseudomonas
      aeruginosa.
AB  - Bacterial cell surfaces play a crucial role in their adhesion to surfaces. In the
      present study, physico-chemical cell surface properties of Pseudomonas
      aeruginosa, isolated from a case of contact lens associated keratitis, are
      determined for mid-exponential and early stationary phase cells and for cells
      after exposure to a lens care solution or after mechanical damage by sonication.
      Exposure to a lens care solution and mechanical cell surface damage reduced the
      cell surface hydrophobicity and water contact angles decreased from 129 degrees
      to 96 degrees and 83 degrees, respectively. Zeta potentials in saline (-9 mV)
      were hardly affected after mechanical damage, but tri-modal zeta potential
      distributions, with subpopulation zeta potentials at -11, -28 and -41 mV, were
      observed after exposure of bacteria to a lens care solution. X-ray photoelectron
      spectroscopy indicated changes in the amounts of oxygen-, nitrogen- and
      phosphorus-rich cell surface components. Mid-exponential phase cells had more
      nitrogen-rich cell surface components than early stationary phase cells, but
      water contact angles and zeta potentials were not very different. In addition,
      mid-exponential phase cells adhered better than early stationary phase cells to
      hydrophobic and hydrophilic substrata in a parallel plate flow chamber. The
      capacity of P. aeruginosa to adhere was decreased after inflicting cell surface
      damage. Exposure to a lens care solution yielded a larger reduction in adhesion
      capacity than sonication, likely because sonication left most of the cells in a
      viable state, in contrast to exposure to a lens care solution. It is argued that
      for clinically relevant experiments, it may be preferable to work with surface
      damaged cells rather than with gently harvested organisms.

PMID- 11311395
TI  - A two-plasmid system for identification of promoters recognized by RNA polymerase
      containing extracytoplasmic stress response sigma(E) in Escherichia coli.
AB  - We have previously established a two-plasmid system in Escherichia coli for
      identification of promoters recognized by RNA polymerase containing a
      heterologous sigma factor. Attempts to optimize this system for identification of
      promoters recognized by RNA polymerase containing E. coli extracytoplasmic stress
      response sigma(E) failed owing to high toxicity of the expressed rpoE. A new
      system for identification of sigma(E)-cognate promoters was established, and
      verified using the two known sigma(E)-dependent promoters, rpoEp2 and degPp.
      Expression of the sigma(E)-encoding rpoE gene was under the control of the AraC
      dependent P(BAD) promoter. A low level of arabinose induced a non-toxic, however,
      sufficient level of sigma(E) to interact with the core enzyme of RNA polymerase.
      Such an RNA polymerase holoenzyme recognized both known sigma(E)-dependent
      promoters, rpoEp2 and degPp, which were cloned in the compatible promoter probe
      plasmid, upstream of a promoterless lacZ alpha reporter gene. This new system has
      proved to be useful for identification of E. coli sigma(E)-cognate promoters.
      Moreover, the system could be used for identification of ECF sigma-cognate
      promoters from other bacteria.

PMID- 11311396
TI  - Real time quantitative PCR and RT--PCR for analysis of Pneumocystis carinii
      hominis.
AB  - Pneumocystis carinii hominis is a common cause of pneumonia in immunocompromised
      patients and particularly in those infected by HIV. Giemsa- and Gomori--Grocott
      stained smears are widely used for detection and quantification of this
      opportunistic fungus obtained from biological samples or from in vitro culture.
      But these methods are fastidious and time-consuming. Thus, instead of performing
      a count of organisms, we focused our attention on the level of specific DNA by a
      quantitative PCR technique. This procedure has the advantage of greater precision
      and more objectivity. To verify the presence of organisms, quantitative RT--PCR
      based on DHFR and a cell cycle mRNA have been developed. In this current study,
      we present a detailed description of these methods and their applications for
      analysis of P. carinii hominis.

PMID- 11311397
TI  - Influence of electrical properties on the evaluation of the surface
      hydrophobicity of Bacillus subtilis.
AB  - The surface hydrophobicity of nine Bacillus subtilis strains in different states
      (spores, vegetative cells, and dead cells) was assessed by water contact angle
      measurements, hydrophobic interaction chromatography (HIC) and bacterial adhesion
      to hydrocarbon (BATH). Electrokinetic properties of B. subtilis strains were
      characterized by zeta potential measurements and found to differ appreciably
      according to the strain. Correlations between HIC data, BATH data and zeta
      potential showed that HIC and BATH are influenced by electrostatic interactions.
      Water contact angle measurements thus provide a better estimate of cell surface
      hydrophobicity. The water contact angle of B. subtilis varied according to the
      strain and the state, the spores tending to be more hydrophobic than vegetative
      cells.

PMID- 11311398
TI  - Rapid detection of viable yeasts and bacteria in wine by flow cytometry.
AB  - The potential of using flow cytometry (FCM) in combination with fluorescent dyes
      for rapidly estimating counts of yeasts and malolactic bacteria in laboratory
      media and wines was examined. In general, there was a good correlation
      (regression coefficient, 0.94) between viable counts of yeasts determined by FCM
      and by standard plate assay. The FCM detection limit of yeasts in YPDE medium and
      in Pinot noir must was 10(3) cells/ml. The lowest bacterial concentration
      detected by FCM was 10(4) cells/ml. When yeast and malolactic bacteria
      populations were simultaneously analysed in wine by FCM without any previous
      sample treatment, difficulties were encountered in the count of bacterial cells
      due to their size, which is similar to natural debries present in wine. However,
      after the optimisation of the sample preparation, the technique appeared
      promising in determining the presence of such microorganisms in wine with one
      single measurement. Because it is rapid and easy to use, flow cytometry can be
      considered a useful method for microbiological quality control in wineries and
      for the investigation of the growth dynamics of microorganisms in wine.

PMID- 11311399
TI  - Specificity for field enumeration of Escherichia coli in tropical surface waters.
AB  - In remote rural areas in developing countries, bacteriological monitoring often
      depends on the use of commercial field media. This paper evaluates a commercial
      field medium used for the enumeration of Escherichia coli in different surface
      waters under primitive field conditions in rural Pakistan. In order to verify the
      field kit, 117 presumptive E. coli isolates have been tested, finding a
      specificity of only 40%. By excluding some strains based on colony colours, the
      calculated specificity could be increased to 65%. Thus, it is suggested that
      prior to use in a tropical environment, the specificity of any commercial medium
      used should be tested with representative tropical isolates, in order to increase
      the specificity.

PMID- 11311400
TI  - Clustering and anchoring mechanisms of molecular constituents of postsynaptic
      scaffolds in dendritic spines.
AB  - Recent technological progress has yielded great amounts of information about the
      molecular constituents of postsynaptic scaffolds in the dendritic spine. Actin
      filaments are major cytoskeletal elements in the dendritic spine, and they
      functionally interact with neurotransmitter receptors via regulatory actin
      binding proteins. Drebrin A and alpha-actinin-2 are two major actin-binding
      proteins in dendritic spines. In adult brains, they are characteristically
      concentrated in spines, but not in dendritic shafts or cell bodies. Thus, they
      are part of a unique postsynaptic scaffold consisting of actin filaments, PSD
      protein family, and neurotransmitter receptors. Localization of NMDA receptors,
      actin filaments, and actin-binding proteins in spines changes in parallel with
      development, and in response to synaptic activity. This raises the possibility
      that clustering and anchoring of these characteristic molecular constituents at
      postsynaptic scaffolds play important roles in spine function. This article
      focuses on the clustering and anchoring mechanisms of NMDA receptors and actin
      filaments, and the involvement of actin-binding proteins, in dendritic spines,
      and the way in which characteristic postsynaptic scaffolds are built up.

PMID- 11311401
TI  - Somatotopic arrangement and corticocortical inputs of the hindlimb region of the
      primary motor cortex in the macaque monkey.
AB  - Using Japanese monkeys, we examined the somatotopic organization of the hindlimb
      region of the primary motor cortex (MI) with intracortical microstimulation. In
      the hindlimb region of the MI, areas representing distal movements (digits and
      ankle joints) were basically surrounded by those representing proximal movements
      (knee and hip joints). Thus, the hindlimb region of the MI has a nested or
      horseshoe-like somatotopic representation. We then examined the topographic
      organization of corticocortical projections to the hindlimb region of the MI by
      the retrograde double-labeling technique: one monkey received paired injections
      of Fast blue (FB) and Diamidino yellow (DY) into hindlimb or forelimb
      representation of the MI, respectively, while two monkeys received those of FB
      and DY into proximal or distal representation of the hindlimb region of the MI,
      respectively. The neurons projecting to the hindlimb region of the MI were
      located in cortical areas largely separate from those projecting to the forelimb
      region of the MI. On the other hand, we found a substantial overlap of
      corticocortical neurons projecting to the proximal and distal parts of the
      hindlimb region of the MI in the dorsal division of the premotor cortex and the
      cingulate motor areas.

PMID- 11311402
TI  - Membrane currents and morphological properties of neurons and glial cells in the
      spinal cord and filum terminale of the frog.
AB  - Using the patch-clamp technique in the whole-cell configuration combined with
      intracellular dialysis of the fluorescent dye Lucifer yellow (LY), the membrane
      properties of cells in slices of the lumbar portion of the frog spinal cord
      (n=64) and the filum terminale (FT, n=48) have been characterized and correlated
      with their morphology. Four types of cells were found in lumbar spinal cord and
      FT with membrane and morphological properties similar to those of cells that were
      previously identified in the rat spinal cord (Chvatal, A., Pastor, A., Mauch, M.,
      Sykova, E., Kettenmann, H., 1995. Distinct populations of identified glial cells
      in the developing rat spinal cord: Ion channel properties and cell morphology.
      Eur. J. Neurosci. 7, 129-142). Neurons, in response to a series of symmetrical
      voltage steps, displayed large repetitive voltage-dependent Na(+) inward currents
      and K(+) delayed rectifying outward currents. Three distinct types of non
      neuronal cells were found. First, cells that exhibited passive symmetrical non
      decaying currents were identified as astrocytes. These cells immunostained for
      GFAP and typically had at least one thick process and a number of fine processes.
      Second, cells with the characteristic properties of rat spinal cord
      oligodendrocytes, with passive symmetrical decaying currents and large tail
      currents after the end of the voltage step. These cells exhibited either long
      parallel or short hairy processes. Third, cells that expressed small brief inward
      currents in response to depolarizing steps, delayed rectifier outward currents
      and small sustained inward currents identical to rat glial precursor cells.
      Morphologically, they were characterized by round cell bodies with a number of
      finely branched processes. LY dye-coupling in the frog spinal cord gray matter
      and FT was observed in neurons and in all glial populations. All four cell types
      were found in both the spinal cord gray matter and FT. The glia/neuron ratio in
      the spinal cord was 0.78, while in FT it was 2.0. Moreover, the overall cell
      density was less in the FT than in the spinal cord. The present study shows that
      the membrane and morphological properties of glial cells in the frog and rat
      spinal cords are similar. Such striking phylogenetic similarity suggests a
      significant contribution from distinct glial cell populations to various spinal
      cord functions, particularly ionic and volume homeostasis in both mammals and
      amphibians.

PMID- 11311403
TI  - Inhibition of neuronal nitric oxide synthase results in neurodegenerative changes
      in the axotomised dorsal root ganglion neurons: evidence for a neuroprotective
      role of nitric oxide in vivo.
AB  - In axotomised adult rat dorsal root ganglion (DRG), many neurons show a marked
      increase in expression of neuronal nitric oxide synthase (nNOS). It has been
      established that NO functions as a neuron-glial signalling molecule by generating
      cGMP in glia cells that surround the neuron in DRG. Furthermore, in cultures of
      dissociated DRG deprived of nerve growth factor, many neurons expressed nNOS and
      cGMP and subsequently died if either enzyme's activity was inhibited suggesting
      that NO-cGMP pathway could be neuroprotective in stressed DRG neurons. This has
      now been tested in vivo. It was found, 10 days after sciatic axotomy that nNOS
      was expressed in 36% of DRG neurons in the L5 and L6 ganglia giving rise to the
      damaged nerve, compared with 6% in contralateral ganglia. Almost all nNOS neurons
      and 24% of non-nNOS neurons expressed c-Jun in their nuclei. Ten days following
      axotomy, treatment with the relatively selective nNOS-blocker, 1-(2
      trifluoromethylphenyl) imidazole (TRIM), caused morphology changes in
      approximately 50% of neurons that consisted of vacuolations, blebbing and highly
      irregular cell boundaries. Sham operated, TRIM treated, nerve-sectioned, vehicle
      treated, and controls did not show these changes. These observations further
      support the view that NO could be neuroprotective in some injured/stressed
      primary sensory neurons.

PMID- 11311404
TI  - Influence of serotonin receptor antagonists on substance P and serotonin release
      evoked by tooth pulp stimulation with electro-acupuncture in the trigeminal
      nucleus cudalis of the rabbit.
AB  - We studied the effect of NAN-190 (5-HT(1A) antagonist), ketanserin (5-HT(2)
      antagonist) and ICS 205-930 (5-HT(3) antagonist) on tooth pulp stimulation (TPS)
      induced 5-HT release and substance P (SP) release in the superficial layers of
      the trigeminal nucleus caudalis (SpVc-I,II) in the presence or absence of electro
      acupuncture (EAP). TPS slightly increased 5-HT release and significantly
      increased SP release. In combination with EAP, TPS-induced 5-HT release was
      remarkably enhanced, whereas SP release was significantly suppressed.
      Pretreatment with NAN-190 (3.5 mg/kg, i.v.) significantly enhanced the increase
      in TPS-induced 5-HT release in the presence of EAP. On the other hand, the
      increase of 5-HT release induced following TPS in the presence of EAP was
      inhibited by pretreatment with ketanserin (2.5 mg/kg, i.v.) and ICS 205-930 (1
      mg/kg, i.v.). When NAN-190 was pre-treated in the animals combined TPS and EAP,
      the amount of SP release was significantly reduced compared with the absence of
      this drug. On the other hand, pretreatment with ketanserin and ICS 205-930
      reversed the inhibitory effect of EAP on the TPS-generated SP release, especially
      ICS 205-930, which remarkably enhanced TPS-induced SP release compared with the
      absence of this drug. On the basis of the obtained results, we concluded that NAN
      190 and ICS 205-930 act on EAP-induced analgesia positively and suppressively,
      respectively, by regulation of TPS-generated SP release through activation of
      their subtype receptors. On the other hand, ketanserin does not affect TPS
      induced 5-HT release and SP release in the presence of EAP.

PMID- 11311405
TI  - Interleukin-1beta induces the expression of lipocortin 1 mRNA in cultured rat
      cortical astrocytes.
AB  - Lipocortin 1 (LC1) has been shown to increase in neuronal damage and act as a
      neuroprotectant and a neurotrophic factor. IL-1beta acts as a mediator of
      inflammation and has been reported as a potent inducer of various neurotrophic
      factors including nerve growth factor and fibroblast growth factor. In this
      study, we investigated the relationship between LC1 and IL-1beta in cultured rat
      astrocytes. Time-and dose-dependent experiments of IL-1beta on rat cortical
      astrocytes in culture revealed that the expression of LC1 mRNA was significantly
      augmented by IL-1beta at 8 h, 10 ng/ml. In addition, IL-1beta evoked an
      extracellular secretion of LC1 without its cytotoxic effects. The effect of IL
      1beta was completely abolished when we treated cells with inhibitor of mitogen
      activated protein kinases (MAPKs) (PD98059) (25 microM), phospholipase A(2)
      inhibitor mepacrine (30 microM) and protein synthesis inhibitor cycloheximide
      (CHX) (10 microg/ml). This suggests that induction of LC1 by IL-1beta is through
      a MAPKs and phospholipaseA(2) pathway and requires protein synthesis. These
      results indicate that IL-1beta released in the central nervous system (CNS)
      injury can stimulate the transcription of the LC1 gene. Subsequent synthesis and
      release of LC1 may provide trophic support to neurons and modulate the action of
      IL-1beta in brain damage.

PMID- 11311406
TI  - Comparison of the spinal anti-nociceptive effects of ES-242-1 and MK-801, two
      different NMDA antagonists, in rats.
AB  - The purpose of this study was to determine whether ES-242-1, a novel N-methyl-D
      aspartate (NMDA) receptor antagonist of microbial origin, has anti-nociception at
      the spinal level and to evaluate how its anti-nociceptive effect differs from
      that of MK-801, a non-competitive NMDA receptor antagonist. Agents were injected
      intrathecally (0.1, 1.0 and 10 microg) through a previously implanted PE tube in
      rats. Formalin (2%, 100 microl) was injected subcutaneously into the left hindpaw
      15 min after each antagonist administration. Licking time as a nociceptive
      behavior was measured in three stages after formalin-injection, such as early
      phase (0-9 min), late first phase (10-29 min) and late second phase (30-60 min).
      In the early phase, the largest dose of ES-242-1 significantly decreased total
      licking time, although MK-801 did not show any significant reduction. With the
      treatment of 1.0 and 10 microg MK-801, total licking time in both late first and
      second phases was significantly suppressed, although the smallest dose (0.1
      microg) of ES-242-1 showed a significant reduction in the late second phase.
      These results indicate that ES-242-1 is highly effective against tonic pain, such
      as inflammatory pain.

PMID- 11311407
TI  - Polysynaptic excitatory pathways induce heterosynaptic depression in the rat
      auditory cortex.
AB  - Short-term plasticity, the effect of a preceding synaptic response on the
      following response in a pair, in layers II/III of the rat auditory cortex slice
      after application of repetitive stimuli to layer IV, was investigated using a
      multichannel extracellular recording system. Paired-pulse depression, which is
      induced to a moderate degree in standard artificial cerebrospinal fluid, was
      markedly facilitated in the presence of bicuculline, a GABA(A) receptor
      antagonist, concurrent with the emergence of a polysynaptic component of the EPSP
      (polyEPSP) in the first response in a pair. This depression (bicuculline
      facilitated synaptic depression, BFSD) was maximal at the minimum interval tested
      (50 ms), reduced as the interval was increased, and persisted beyond an interval
      of 2 s. The occurrence of BFSD was dependent on the presence of a polyEPSP
      regardless of the presence of the monosynaptic component of the EPSP, indicating
      that BFSD is induced by a heterosynaptic mechanism. D-AP5, an NMDA receptor
      antagonist, partially eliminated polyEPSPs and reversed BFSD. These results
      suggest that activation of polysynaptic excitatory pathways induces a
      heterosynaptic depression in the range of a few seconds and that NMDA receptor
      activity is involved in this heterosynaptic depression.

PMID- 11311408
TI  - Analysis of spontaneous EPSCs in retinal horizontal cells of the carp.
AB  - Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under Whole
      cell voltage clamp from carp type 1 horizontal cells (H1 cells) uncoupled by
      dopamine in retinal slices. Red light steps, which hyperpolarise cones and reduce
      glutamate release, induced outward current responses accompanied by a suppression
      of sEPSCs. sEPSCs decayed exponentially with a mean time constant of 0.71+/-0.07
      ms and had a reversal potential near 0 mV. Power spectral analysis of sEPSCs
      revealed a similar decay time constant. They were suppressed by a non-NMDA
      receptor antagonist, CNQX at 10 microM, and a relatively specific AMPA receptor
      antagonist, GYKI52466 at 20 microM. The presence of sEPSCs suggests that the
      release of glutamate from cone synaptic terminals is vesicular. The reduction in
      mean sEPSC frequency with red light was not accompanied by a significant change
      in the mean sEPSC conductance increase (482+/-59 pS), suggesting that a decrease
      in the vesicular release rate from cones does not alter the vesicular glutamate
      concentration (quantal contents). The results suggest that the spontaneous events
      in H1 cells were contributed by non-NMDA (possibly AMPA) type glutamate receptors
      modulated by the red cone input.

PMID- 11311409
TI  - A possible functional organization of the corticostriatal input within the weakly
      correlated striatal activity: a modeling study.
AB  - Recently, it was reported in an in vivo study that pairs of the striatal
      projection neurons (medium-sized spiny neurons) of the basal ganglia show
      asynchronous spiking within weakly-correlated subthreshold depolarized states. In
      this computational study, we investigate a possible functional organization of
      corticostriatal inputs that accounts for the experimental observations within
      known anatomical and physiological constraints. In a pair of medium-sized spiny
      neurons, a small fraction of corticostriatal fibers is common to both neurons. To
      explain the weak correlations in sub- and supra-threshold activities of the
      neuron pair, we postulate that the two input channels, common or specific to the
      individual neurons, have distinct functional roles. The common input channel
      delivers random spike trains and is primarily responsible for the initiation and
      maintenance of the depolarized states. In contrast, the input through the neuron
      specific channels elicit postsynaptic spikes by delivering intermittently
      synchronized spikes. The results of this model were compared with those derived
      from a newly-performed analysis of the previous double-intracellular recording
      data. We show that the behavior of this model agrees qualitatively and
      quantitatively with that of the medium-sized spiny neurons observed in the
      experiments in a certain range of the coincident time window.

PMID- 11311410
TI  - Dissociation of systemic and hippocampal modulation of rat locomotor activity by
      5-HT(2C) receptors.
AB  - In the present study, the ability of 5-hydroxytryptamine(2C) (5-HT(2C)) receptors
      in the hippocampus to enhance locomotor activity in rats was investigated by
      local infusion. Intraperitoneal injection of the selective 5-HT(2C) antagonist SB
      242084 (1 mg/kg) significantly increased rats motor activity, while the effects
      of non-selective 5-HT(2C) agonist m-chlorophenylpiperazine (m-CPP, 10 mg/kg;
      i.p.) on motor activity were lower than those of the control group. In the day
      hours, the local infusion of non-selective 5-HT(2C) agonist, m-CPP (1.0 mM) into
      the bilateral hippocampus via microdialysis probes increased locomotor activity
      in contrast with intraperitoneal injection. This increase was completely reversed
      by the combined infusion of the selective 5-HT(2C) antagonist SB 242084 (100 mM).
      In the night hours, the local infusion of SB 242084 (100 mM) into the bilateral
      hippocampus significantly inhibited the nocturnal hyperactivity, which was
      reversed by the combined infusion of m-CPP. The present study demonstrates that
      the 5-HT(2C) receptors in the hippocampus act to increase rat locomotor activity.

PMID- 11311411
TI  - Preface.

PMID- 11311412
TI  - Sucking motivation and related problems in calves.
AB  - Since survival of the young mammals depends on sucking success, it is assumed
      that sucking motivation must be strong and that sucking deprivation would result
      in frustration which could have a negative impact on their welfare. This concern
      as well as that regarding cross-sucking between calves and intersucking between
      older animals has stimulated research on the motivation of calves for non
      nutritive sucking. Non-nutritive sucking is elicited by the ingestion of milk,
      and the lactose concentration in milk, rather than that of fat or protein, is the
      main factor stimulating non-nutritive sucking. Every time a calf drinks milk, it
      is stimulated to suck and deprivation of sucking may interfere with digestive
      processes or satiety. To understand the behaviour of the calf during nutritive
      sucking, we examined the effects of milk flow on calves' sucking and butting an
      artificial feeding system. Slowing and stopping the flow rate stimulates butting
      and can lengthen the duration of sucking for the meal. It also stimulates the
      calf to switch teats when a second teat is available. These findings are well
      correlated to our observations of the calf suckling a cow in experimental
      manipulations. The duration of the meal is not correlated with milk intake, but
      it is influenced by milk availability and how hungry the calf is. Furthermore,
      calves will butt more often when there is less milk available in the dam's udder,
      presumably because milk flow is slower. Consequently, it is the occurrence of
      butting rather than sucking duration that would be a good indicator of milk
      intake when the calf is suckling the dam. Finally, we recommend a combination of
      slower milk flow and hay feeding and the provision of a non-nutritive artificial
      teat to reduce the occurrence of cross-sucking following a milk meal.

PMID- 11311413
TI  - Effect of milkflow rate and presence of a floating nipple on abnormal sucking
      between dairy calves.
AB  - The aim of this study was to investigate if access to an artificial teat compared
      to an open bucket would decrease abnormal sucking in calves held in pairs, and if
      the calves would perform less abnormal sucking if they spent more time drinking
      or sucking the milk. In total 16 calves of Swedish Red and White cattle housed in
      pairs were used. The eight groups were given 2.5l of whole milk per calf, twice a
      day in one of the following treatments; bucket with fast flow (control), bucket
      with slow flow, floating nipple with fast flow and floating nipple with slow
      flow. All groups were subjected to the four different treatments in a random
      balanced order. Two buckets were connected with a rubber pipe in order to control
      the milk flow. In the fast treatments, the milk poured from one bucket to the
      other in 40s, and in the slow treatments the milk poured from one bucket to the
      other in 10min. Each group had the treatment for 6 days before behavioural
      observations were done on day 7. These were made by instantaneous recordings at
      20s intervals for 30min, starting when the calves received their milk in the
      morning and afternoon. The number of recordings of abnormal sucking was lower
      than the control in all treatments (P<0.001). The lowest recording of abnormal
      sucking was found, when the calves had both a floating nipple and a slow flow.
      Sucking on other objects in the pen had the highest number of recordings, when
      they had a nipple and a fast flow (P<0.01), but the sucking on the empty nipple
      represented 95% of this category. The calves tended to lick and bite more on the
      bucket, the nipple and pen fittings in the two treatments with fast flow (P<0.1)
      than in the slow treatment with nipple. It is concluded that both the performance
      of sucking and the time taken to ingest milk are important in order to decrease
      abnormal sucking between calves.

PMID- 11311414
TI  - Effects of amount of milk, milk flow and access to a rubber teat on cross-sucking
      and non-nutritive sucking in dairy calves.
AB  - The aim of this study was to test the effects of different amounts of milk, flow
      rate of milk, and access to a teat after milk intake on non-nutritive sucking on
      an empty teat and on cross-sucking on other calves in Bos taurus dairy calves. An
      additional aim was to test if calves prefer to perform non-nutritive sucking on a
      teat with the taste of milk or on a clean teat. First experiment involved 11
      groups of three calves during gradual decrease from 5 to 2.5 and 1 to 0l of whole
      milk per meal twice daily. Milk flow was either 0.5 or 1l/min, and the teat
      buckets were either left or removed after milk intake. When the calves were fed
      with 5l of milk, non-nutritive sucking and cross-sucking decreased (P<0.001),
      compared to 1 and 2.5l. Removing the empty teat after milk intake increased cross
      sucking (P<0.001). Slow milk flow reduced non-nutritive sucking after milk intake
      (P<0.05), but did not influence cross-sucking. Duration of recorded milk intake
      was similar with fast flow and 5l of milk, compared to slow flow and 2.5l of
      milk. The latter combination increased non-nutritive sucking and cross-sucking,
      suggesting that amount of milk is more important than duration of milk
      intake.Second experiment was carried out on 12 individually kept calves. The
      calves received 2.5l of milk either in an open bucket, in a rubber teat bucket,
      or half/half in both buckets. When not used for feeding, the open bucket and the
      teat bucket were filled and emptied again to make them 'tasty' with some drops of
      milk. The tasty teat bucket was either removed or present after milk intake. The
      calves had always access to a second clean teat bucket. Source of milk had no
      influence on recorded behaviour after milk intake. The tasty teat was sucked for
      twice as long as the clean one when both teats were present (P<0.001). When the
      tasty teat was removed, the calves increased sucking on the clean teat (P<0.001),
      but decreased total time spent sucking (P<0.001). We conclude that a high amount
      of milk and the presence of the teat bucket after milk intake reduces cross
      sucking, and that a clean teat is less effective in encouraging calves to suck
      than a teat with taste of milk.

PMID- 11311415
TI  - Reduction in cross-sucking in calves by the use of a modified automatic teat
      feeder.
AB  - Cross-sucking may be a problem in group-housed calves fed by automatic teat
      feeders. In the present study, the behaviour of calves fed by a conventional
      feeder with an open feeding stall (n=15 calves) was compared with the behaviour
      of calves fed by a modified feeder, closing in the rear after the calf has
      entered (n=14 calves). It was found that the calves fed by the feeder with the
      closed stall stayed longer in the feeding stall following milk ingestion
      (P<0.001), showed longer bouts of non-nutritive sucking directed to the teat
      after milk ingestion (P<0.005) and performed less cross-sucking in the first
      15min after milk ingestion (P<0.001) than calves fed by the feeder with the open
      stall. The design of the feeder had, however, no significant influence on the
      incidence of cross-sucking performed without close temporal association with milk
      ingestion. As the modification in the feeding stall reduces cross-sucking and is
      not costly, it should be feasible to introduce it in practice.

PMID- 11311416
TI  - Oxytocin facilitates behavioural, metabolic and physiological adaptations during
      lactation.
AB  - The aim of this article is to propose that oxytocin not only stimulates milk let
      down, but also adapts behaviour and physiology to facilitate lactation in mammals
      including dairy cattle. Circulating oxytocin as well as neurogenic oxytocin
      participates in these regulatory processes. In short, oxytocin stimulates
      maternal interaction and attachment between mother and young. It also
      participates in the metabolic prerequisites for milk production by e.g.
      stimulating glucagon release and thereby, mobilisation of glucose. Digestive and
      anabolic aspects of metabolism are also stimulated, e.g. by increased vagal nerve
      activity. Adaptations consistent with an antistress like pattern are also
      induced. Cortisol levels are decreased as well as blood pressure, and behaviours
      characterised by calm, reduced levels of anxiety and more social activity are
      promoted. These effects seem to be present in monogastric animals as well as in
      ruminants. The expression of various aspects of these adaptations vary according
      to the special needs and living environmental circumstances of different species.
      The mechanisms behind the effect spectrum of oxytocin are being explored in other
      experimental models. A second aim of this paper is to suggest that efficiency of
      lactation can be promoted by facilitating oxytocin release in connection with
      milking by enhancing the amount of sensory stimulation.

PMID- 11311417
TI  - The effects of conditioning to suckling, milking and of calf presence on the
      release of oxytocin in dairy cows.
AB  - The aim of the study was to record the oxytocin (OT) release during milking (M)
      without or with calf presence, suckling (S) and finally calf removal just before
      the next milking in cows during postpartum or early lactation periods.
      Furthermore, the release of OT was examined during S and M in unknown
      surroundings (parlour). A total of 20 Brown Swiss cows kept under loose housing
      environment were used in our experiment. In both periods, the cows were milked
      twice daily at 07.00 and 18.00h and suckled three times daily at 09.00, 14.00 and
      20.00h in the stall (tie housing). In the postpartum period, 13 cows were suckled
      and milked in the presence of their calves in the stall for the first 5 days of
      postpartum. Five from seven primiparous cows were additionally suckled by their
      own calves in the parlour on day 5 at 20.00h. On day 6, calves were separated and
      moved from mothers to the calf barn 10min before morning M. After evening milking
      cows were relocated to the herd within the same stable and milked in the parlour
      for a period of 4 weeks without contact to their calf. For control, additional
      seven primiparous cows without calf presence (not suckled) were also milked in
      the tie housing. In the early lactation period, suckled cows were moved back to
      the tie housing 2 days before the start of two consecutive days of S by their own
      calves and milking. Afterwards, 10min before M calves were separated again.
      Before S, two consecutive M were considered as controls. Results: The S stimulus
      during postpartum resulted in a higher OT release as compared with M in the calf
      presence and M after calf separation but not during M of not suckled cows. S in
      parlour reduced OT release. However, when not suckled primiparous cows were first
      milked in parlour, OT release was more reduced and in some cows total inhibition
      was observed. In early lactation during the first S, release of OT was lower than
      during control M, but increased gradually with repeated S and reached a maximum
      already on the second day. After two S, during evening M, the M related OT
      release was reduced as compared with controls. Calf removal 10min before M
      reduced OT release as compared with control M or M in calf presence. In
      conclusion, the calf presence and its removal can negatively influence OT
      secretion during M. Conditioning to machine milking caused a short-term reduction
      of OT release during first suckling, which normalised within 1 day.

PMID- 11311418
TI  - Naloxone cannot abolish the lack of oxytocin release during unexperienced
      suckling of dairy cows.
AB  - To evaluate the role of opioids for the regulation of oxytocin release in
      response to teat stimulation, 10 brown-Swiss dairy cows were randomized to two
      experiments during mid of lactation. In the first experiment, four cows without
      previous suckling experience were suckled by an alien calf between two normal
      milkings. Before and during milking or suckling, frequent blood samples were
      collected via a jugular cannula for determination of oxytocin and beta-endorphin.
      In the second experiment, six cows were treated with naloxone or saline, 10min
      before the start of the first or second suckling, respectively. The collected
      blood samples were assayed for oxytocin.In the first experiment, the plasma
      levels of beta-endorphin were elevated during and after the unexperienced
      suckling in three cows, but not in the fourth cow, and the release of oxytocin
      during suckling was markedly reduced, suggesting no release of alveolar milk. In
      the second experiment, the release of oxytocin during suckling was again
      significantly reduced. Pretreatment with naloxone before suckling did not
      completely abolish the adverse effect of suckling and the oxytocin plasma level
      did not increase to levels comparable with control milking.In emotional stress
      situations, the release of oxytocin from the pituitary is inhibited with
      simultaneously elevated beta-endorphin plasma levels. Although there is some
      evidence for a regulatory role of opioids for the release of oxytocin, other
      mediators are suggested to be more potent in regulating oxytocin under stress
      conditions.

PMID- 11311419
TI  - Consequences of different suckling systems for reproductive activity and
      productivity of cattle in tropical conditions.
AB  - The late onset of ovarian activity in mature cattle raised under tropical
      conditions is the major setback impeding a sound reproductive performance needed
      for the increasing demand of livestock products in the area. The effect of
      suckling has been circled as one of the most important factors impeding ovarian
      activity. Farmers in this region have used the most diverse set of management
      tools to overcome the suckling effect without compromising reproduction, the
      health of the calf, growth until weaning, milk production and a correct function
      of the mammary gland.Farmer interventions can be divided in: (1) early weaning
      (about 1 week of age); (2) weaning at 1, 3 or 5 months; (3) restricted suckling;
      (4) partial weaning. These systems can be affected by the breed of the animal,
      the location of the enterprise, infrastructure in the farm, time of the year and
      system of separation. The advantages and disadvantages of these systems are
      discussed in this review.

PMID- 11311420
TI  - Behaviour of Zebu and crossbed cows in restricted suckling groups.
AB  - The aim of this study was to investigate whether Zebu (Bos indicus) and crossbred
      (Bos indicusxBos taurus) cows differ in maternal related behaviour during
      restricted group suckling. The behaviours of 20 Zebu and 16 crossbred cows were
      recorded during two 30min sessions each day after milking when their calves were
      present for suckling, for a time period of 2 weeks per month for 6 months
      postpartum. The main activity in both breeds during the 0.5h observation sessions
      was suckling. However, the two breeds differed significantly in several
      behavioural aspects. The Zebu cows had longer total duration of suckling than the
      crossbred cows, per 30min session, 11.8 and 9.4min, respectively. The separate
      suckling bouts were longer in the Zebu cows (2.8min in Zebu and 2.3min in
      crossbred) and this breed also had more suckling bouts than the crossbred per
      session, 3.8 and 3.2, respectively. Zebu cows stayed in close contact with their
      calves for longer time and directed more agonistic actions against alien calves
      and cows than the crossbred cows.

PMID- 11311421
TI  - Effects of different suckling systems on milk production, udder health,
      reproduction, calf growth and some behavioural aspects in high producing dairy
      cows - a review.
AB  - This article discusses the consequences of different suckling systems in the
      industrial countries for the milk production, udder health, reproduction and
      behaviour of high producing dairy cows and the effects on the gain, health and
      behaviour of the calves. The suckling systems are divided into three different
      categories depending on the purpose and duration of the suckling period. Long
      term suckling with or without additional milking covering the period where the
      calf has a nutritional need for milk, and short-term suckling, where cow and calf
      are kept together in the colostrum period only.Long-term suckling without
      additional milking in early lactation can in some situations stimulate the
      subsequent milk production to a greater extent than milking alone. No clear or
      significant differences can be found between restricted and free suckling
      systems. Most experiments show that suckling decreases the risk of mastitis in
      the suckling period and in some cases even for some time after the suckling has
      been terminated. Suckling and milking during the same period is not advantageous
      in production turns because of a very poor ejection of milk. Long-term suckling
      can increase the post-partum interval until first heat, in some cases until the
      end of the suckling period. However, as the cows appear to be more fertile, the
      net effect on reproduction is small. The suckled calves are usually healthy with
      a high daily gain. Short-term suckling have more advantages than disadvantages on
      production, health and behaviour of both the cow and the calf compared to an
      immediate separation after birth.

PMID- 11311422
TI  - Mother-young relationships in Belgian Blue cattle after a Caesarean section:
      characterisation and effects of parity.
AB  - The systematic use of Caesarean section in "double muscled" Belgian Blue cattle
      can induce ethical concerns. The aims of the following study was to characterise
      mother-young relationships in such a situation and to assess the effect of
      parity. Fifteen heifers and 15 cows of the Belgian Blue breed were observed using
      video recording when isolated with their calf during the 3 days following
      Caesarean, a rapid surgery with rare occurrence of aggressive behaviour and no
      sign of cows' discomfort or weakness. All calves were bottle-fed mother's
      colostrum once before first suckling occurred. Heifers' calves received a
      supplementary number of three such artificial meals, while cows' calves needed
      only one. The overall median time to first licking of the calf by the mother was
      3.3min without any effect of parity. The mean licking frequency was 29.2+/-15.8
      per 24h: heifers licked their calf less frequently than cows, respectively 23.4+/
      15.3 per 24h versus 35.1+/-14.5 per 24h (P<0.05). The mean total licking duration
      was 42.2+/-25.9min per 24h: there was no significant difference between heifers
      and cows. The overall median time to first suckling was 6.1h, without any effect
      of parity. The mean suckling frequency was 8.4+/-4.8 per 24h: for half of these
      suckling bouts, the calf was situated on the left side of the mother, i.e. the
      side of the scar. The suckling frequency was negatively correlated with the
      number of artificial meals (r(s)=-0.45,P<0.05). Heifers suckled their calf less
      often than cows, respectively 6.1+/-3.1 per 24h versus 10.7+/-5.2 per 24h
      (P<0.01), but the left side proportion was not significantly different. The mean
      suckling total duration was 35.3+/-21.0min per 24h. The calf was on the left side
      of the mother during half of this time. Heifers suckled their calf during a
      shorter time than cows, respectively 26.9+/-20.0min per 24h versus 43.8+/-19.1min
      per 24h (P<0.05), and the left side proportion was not significantly different.
      Licking frequency and suckling duration were positively correlated
      (r=0.43,P<0.05). Only 10% of the mothers (one heifer and two cows) butted their
      calf and kicking was never observed. Despite the difficult comparison with
      results of the literature according to various methodologies, mother-young
      relationships were considered as similar to those reported after natural calving.
      In our study, cows can be considered as better mothers than heifers.

PMID- 11311423
TI  - Replication of a chimeric origin containing elements from Epstein-Barr virus ori
      P and bovine papillomavirus minimal origin.
AB  - The bovine papillomavirus E2 protein is a multifunctional protein that activates
      viral transcription, co-operates in initiation of viral DNA replication, and is
      required for long-term episomal maintenance of viral genomes. The EBNA1 protein
      of Epstein-Barr virus is required for synthesis and maintenance of Epstein-Barr
      virus genomes. Both viral proteins act through direct interactions with their
      respective DNA sequences in their origins of replication. The chimeric protein
      E2:EBNA1, which consists of an transactivation domain of E2 and DNA binding
      domain of EBNA1 supported the replication of the chimeric origin that contained
      EBNA1 binding sites in place of the E2 binding sites principally as full-length
      E2 did in the case of papillomavirus minimal origin. This indicates that the
      chimeric protein E2:EBNA1 is competent to assemble a replication complex similar
      to the E2 protein. These data confirm the earlier observations that the only part
      of E2 specifically required for its activity in replication is the N-terminal
      activation domain and the function of the DNA binding domain of E2 in the
      initiation of replication is to tether the transactivation domain of E2 to the
      origin of replication.

PMID- 11311424
TI  - Analysis of sequences involved in IE2 transactivation of a baculovirus immediate
      early gene promoter and identification of a new regulatory motif.
AB  - Opep-2 is a unique baculovirus early gene that has only been identified in the
      Orgyia pseudotsugata multiple capsid nucleopolyhedrovirus (OpMNPV). Previous
      analyses have shown this gene is expressed at very early times post-infection
      (p.i.) but is shut down by 36-48 h p.i. The promoter of opep-2 therefore,
      represents a class of early genes that is temporally regulated. In this study, a
      detailed analysis of the opep-2 promoter is performed to analyze the role
      individual motifs play in early gene expression. A new 13 base pair regulatory
      element was identified and shown to be essential in controlling high-level
      expression of this gene. In addition, mutational analysis revealed that GATA and
      CACGTG motifs, which have been shown to bind cellular factors in Sf9 and Ld652Y
      cells, played minor roles in influencing opep-2 expression in the absence of
      other viral factors. The OpMNPV transactivator IE2 causes a significant
      activation of the opep-2 promoter. Cotransfection of an extensive number of
      promoter deletions and mutations did not show any sequence specificity for IE2
      transactivation. This is the first detailed analysis of the sequence requirements
      for IE2 transactivation, and these results suggest that IE2 does not bind
      directly to specific elements in the opep-2 promoter.

PMID- 11311425
TI  - Restoration of secondary hairpin II is associated with restoration of infectivity
      of a non-viable recombinant viroid.
AB  - Mutagenesis and/or construction of recombinants by exchange of genomic regions
      between parental molecules constitute powerful tools for the study of viroids.
      However, a large proportion of such modifications results in molecules, which
      have lost their infectivity. Such is the case for a recombinant viroid named
      CECS, obtained by replacing the right half of a citrus exocortis viroid (CEVd) by
      the same region from chrysanthemum stunt viroid (CSVd). In an effort to recover
      viable infectious progeny from this recombinant, tomato plants were inoculated
      with an Agrobacterium strain carrying a dimer of the CECS viroid in positive
      orientation under the control of the CaMV 35S promoter. About 20% of the plants
      treated in this way were found to be infected with a replicating viroid, which
      was further propagated. Sequence analysis of six cloned full-length cDNAs derived
      from progeny molecules revealed the presence of mutations as compared with the
      parental CECS sequence. However, only two types of mutations were consistently
      recovered in all progeny molecules, the addition of a G in a string of four at
      positions 70-73, a mutation frequently observed in CEVd isolates and mutations
      leading to the restoration of the correct base pairing in secondary hairpin II.
      These results show that agro-infection is a suitable technique for the recovery
      of viable molecules from non-infectious viroid mutants and confirm that the
      ability to form secondary hairpin II is a prerequisite for viroid infectivity.

PMID- 11311426
TI  - Phylogenetic analysis of Brazilian Flavivirus using nucleotide sequences of parts
      of NS5 gene and 3' non-coding regions.
AB  - Viruses of the genus Flavivirus, which are arboviruses, of the Flaviviridae
      family, are amongst the most important agents of infectious disease in Brazil,
      causing human infections with a high morbility and mortality. In this work, the
      phylogeny of 14 virus amplicon sequences that were obtained by RT-PCR with
      universal primers for mosquito-borne Flavivirus were studied. The amplicons
      included a region of the Flavivirus genome of 129 nucleotides at the 3' terminus
      of the NS5 gene and the 145 initial nucleotides of the 3' non-coding region (NS5
      3'NCR). Based on phylogenetic trees, most Brazilian Flaviviruses were grouped
      into two main branches, including a yellow-fever branch and a second main branch
      divided into a dengue branch that in its turn is subdivided into serotype 1, 2
      and 4 branches, and another (Japanese Encephalitis Virus Complex) branch
      including SLE and Ilheus. Rocio and Cacipacore viruses were included in the
      Japanese Encephalitis Virus Complex branch in one of the two phylogenetic trees.
      Iguape virus appears in phylogenetic trees as a separate distant branch.

PMID- 11311427
TI  - Inhibition by prostaglandin PGA1 on the multiplication of influenza virus is a
      dose-dependent effect.
AB  - Cyclopentenone prostaglandins (PGs), are strong inhibitors of the multiplicative
      cycle of a wide variety of enveloped RNA and DNA viruses. Their antiviral
      activity is generally associated with alterations in the synthesis or maturation
      of specific virus proteins. In this report, we describe the effect of
      cyclopentenone PGA1 on the replication of influenza A virus Ulster 73 in LLC-MK2
      cells. PGA1 was found to inhibit viral replication in a dose-dependent fashion
      and virus particle yield was reduced at a PGA1 concentration, which did not
      suppress protein synthesis in mock-infected cells. The kinetic of late viral
      protein synthesis was delayed in PGA1-treated cells till 10 h post-infection;
      after that period, viral polypeptide synthesis appeared to be similar in PGA1
      treated as well as untreated cells both infected by Ulster 73 virus. This finding
      suggests that PGA1 might interfere with one or more events in the viral
      multiplicative cycle such as protein synthesis and assembly, correct insertion of
      virus polypeptides into the cell membrane and, or maturation of Ulster 73 virion
      particles. In particular, inhibition of viral replication in LLC-MK2 cells by
      PGA1 is accompanied by the induction of a cellular polypeptide of 70K molecular
      weight. We identified this cell protein as a heat shock protein (HSP) related to
      the inducible isoform of HSP 70, a polypeptide of 72K molecular weight. Induction
      of this polypeptide by PGA1 was found to be dose-dependent and a substantial
      accumulation could be seen at a PGA1 concentration that did not inhibit cell
      protein synthesis in uninfected cells. HSP 70 synthesis started after the
      beginning of PGA1 treatment and remained at the same level for at least 10 h,
      leading us to hypothesize that the delay of production of late Ulster 73 proteins
      could be the consequence of HSP 70 synthesis. These results suggest that HSP 70
      could play a role in the antiviral activity of cyclopentenone PGA1 in LLC-MK2
      cells.

PMID- 11311428
TI  - Phylogenetic and antigenic characterization of new fish nodavirus isolates from
      Europe and Asia.
AB  - Nodaviruses are widespread causative agents of viral nervous necrosis in fish.
      Based on the coat protein sequence, fish nodaviruses are categorized into four
      different genotypes. In this study, we present data on the phylogenetic and
      antigenic characterization of 12 new isolates, eight European and four of Asian
      origin, from farmed and wild species of fish. Phylogenetic analysis based on the
      nucleotide sequence (688 bases) of the coat protein classified the majority of
      these new isolates to the RGNNV genotype. Geographic or host-species
      specificities were not revealed by this study. Neutralizing assay experiments,
      further confirmed the genotypic classification, supporting the possibility that
      the different nodavirus genotypes can also be serologically distinguishable.

PMID- 11311429
TI  - Comparison of the sialic acid binding activity of transmissible gastroenteritis
      coronavirus and E. coli K99.
AB  - Transmissible gastroenteritis coronavirus (TGEV) and Escherichia coli K99 are
      both enteropathogenic for pigs with infections being most severe in neonate
      animals. For both microorganisms, a sialic acid binding activity has been shown
      to be an essential pathogenicity factor. Here we demonstrate with
      haemagglutination and haemagglutination-inhibition assays that TGEV and E. coli
      K99 differ in their sialic acid binding activities with respect to the type and
      amount of sialic acid residues required on the erythrocytes surface as well as
      with respect to the type of sialoglycoconjugate preferentially recognized.
      Intestinal mucins from piglets (12-14 days old) and adult animals were shown to
      inhibit TGEV to the same extent. From our results we conclude that E. coli K99
      and TGEV interact with different sialoglycoconjugates to establish an intestinal
      infection. The implications for the enteropathogenicity of TGEV are discussed.

PMID- 11311430
TI  - Genetic and serotypic characterization of Sin Nombre-like viruses in Canadian
      Peromyscus maniculatus mice.
AB  - In Canada, hantavirus infected deer mice (Peromyscus maniculatus) have been
      collected from British Columbia to Newfoundland. Partial sequencing of G1 and N
      protein encoding regions from Canadian Peromyscus maniculatus-borne hantaviruses
      demonstrated the existence of significant genotypic divergence among strains.
      Phylogenetic analysis showed that Sin Nombre (SN)-like viruses from eastern and
      western Canadian deer mice can be divided into at least two broad-based
      genogroups. Sequencing of mitochondrial DNA from infected deer mice originating
      from various eastern and western provinces showed that SN-like virus genogroups
      appeared to be associated with distinct haplotypes of mice. Sera from deer mice
      infected with eastern and western viral genotypes neutralized the Sin Nombre
      virus strain, Convict Creek 107, but not the New York 1 hantavirus. Despite the
      genetic heterogeneity of Canadian SN-like strains these hantaviruses do not
      appear to define unique hantavirus serotypes.

PMID- 11311431
TI  - Detection and multigenic characterization of a novel gammaherpesvirus in goats.
AB  - Evidence for the existence of a caprine gammaherpesvirus was obtained by analysis
      of peripheral blood leucocytes of goats with PCR assays that target the
      herpesvirus genes encoding the glycoprotein B (gB), the DNA polymerase (DPOL) and
      the terminase (TERM) with degenerate and deoxyinosine-substituted primers. A
      contiguous 3.6 kbp sequence extending from the gB to the DPOL gene was then
      determined with specific primers. All sequences (gB, DPOL and TERM) showed a
      close relationship with the corresponding genes of the Gammaherpesvirinae.
      Alignment of amino acid sequences revealed a particularly high percentage of
      identity with the ovine herpesvirus type 2 (>83%), followed by the alcelaphine
      herpesvirus 1 (>76%) and the bovine lymphotropic herpesvirus (>61%). Phylogenetic
      analyses confirmed these relationships. The putative novel goat herpesvirus from
      which these sequences originate was tentatively designated caprine herpesvirus 2.
      This virus is the first gammaherpesvirus recognized in goats.

PMID- 11311432
TI  - Correlation between phylogenetic structure and function: examples from deep-sea
      Shewanella.
AB  - The genus Shewanella is one of the typical deep-sea bacterial genera. Two
      isolated deep-sea Shewanella species, Shewanella benthica and Shewanella
      violacea, were found to be able to grow better under high hydrostatic pressure
      conditions than at atmospheric pressure. These species are not only piezophilic
      (barophilic), but also psychrophilic. Many psychrophilic and psychrotolerant
      Shewanella species have been isolated and characterized from cold environments,
      such as seawater in Antarctica or the North Sea. Some of these cold-adapted
      Shewanella were shown to be piezotolerant, meaning that growth occurs in a high
      pressure habitat. In this review, we propose that two major sub-genus branches of
      the genus Shewanella should be recognized taxonomically, one group characterized
      as high-pressure cold-adapted species that produce substantial amounts of
      eicosapentaenoic acid, and the other group characterized as mesophilic pressure
      sensitive species.

PMID- 11311433
TI  - Inhibition of methanogens increases photo-dependent nitrogenase activities in
      anoxic paddy soil amended with rice straw.
AB  - The interaction between phototrophic dinitrogen fixers and methanogens was
      examined in soil slurries amended with rice straw using 2-bromoethanesulfonic
      acid (BES), a specific methanogenic inhibitor. Slurries incubated in light
      increased phototrophic nitrogenase activity (acetylene reducing activity), and
      showed growth of phototrophic purple bacteria and reduction of CH(4) emission,
      indicating outcompetition of purple bacteria with methanogens in photic zones.
      Adding BES effectively inhibited methane production and markedly increased
      phototrophic acetylene reducing activity accompanied with acetate accumulation,
      but did not affect populations of purple bacteria in the slurries. More acetate
      accumulated in the inhibited slurries incubated in dark. We suggest that
      increased availability of organic substrates for purple bacteria after stopping
      methanogenic consumption by BES caused the increased phototrophic acetylene
      reducing activity. These results indicate that, after purple bacteria grow
      enough, performance of their N(2) fixation may be limited by substrate
      availability, which methanogenesis may profoundly influence.

PMID- 11311434
TI  - Effect of Photorhabdus luminescens phase variants on the in vivo and in vitro
      development and reproduction of the entomopathogenic nematodes Heterorhabditis
      bacteriophora and Steinernema carpocapsae.
AB  - Photorhabdus luminescens (Enterobacteriaceae) is a symbiont of entomopathogenic
      nematodes Heterorhabditis spp. (Nematoda: Rhabditida) used for biological control
      of insect pests. For industrial mass production, the nematodes are produced in
      liquid media, pre-incubated with their bacterial symbiont, which provides
      nutrients essential for the nematode's development and reproduction. Particularly
      under in vitro conditions, P. luminescens produces phase variants, which do not
      allow normal nematode development. The phase variants were distinguished based on
      dye absorption, pigmentation, production of antibiotic substances, occurrence of
      crystalline inclusion proteins and bioluminescence. To understand the
      significance of the phase shift for the symbiotic interaction between the
      bacterium and the nematode, feeding experiments tested the effect of homologous
      and heterologous P. luminescens phase variants isolated from a Chinese
      Heterorhabditis bacteriophora (HO6), the Heterorhabditis megidis type strain from
      Ohio (HNA) and the type strain of Heterorhabditis indica (LN2) on the in vivo and
      in vitro development and reproduction of the nematode species H. bacteriophora
      (strain HO6) and another rhabditid and entomopathogenic nematode, Steinernema
      carpocapsae (A24). In axenically cultured insect larvae (Galleria mellonella) and
      in vitro in liquid media, H. bacteriophora produced offspring on phase I of its
      homologous symbiont and on the heterologous symbiont of H. megidis, but not on
      the two corresponding phase II variants. In solid media, nematode yields were
      much lower on phase II than on phase I variants. On the heterologous phase I
      symbiont isolated from H. indica the development of H. bacteriophora was not
      beyond the fourth juvenile stage of the nematode in any of the media tested, but
      further progressed on phase II with even a small amount of offspring recorded in
      solid media. Infective juveniles of S. carpocapsae did not develop beyond the J3
      stage on all phase I P. luminescens. They died in phase I P. luminescens isolated
      from H. bacteriophora. Development to adults was recorded for S. carpocapsae on
      all phase II symbionts and offspring were produced in all media except in liquid.
      It is concluded that a lack of essential nutrients or the production of toxins is
      not responsible for the negative impact of homologous phase II symbiont cells on
      the development and reproduction of H. bacteriophora. The infective juveniles of
      H. bacteriophora retained cells of the homologous phase I symbiont, but not phase
      II cells and cells from heterologous symbionts, indicating that the transmission
      of the symbiont by the infective juvenile is selective for phase I cells and the
      homologous bacterial associate.

PMID- 11311435
TI  - The microbial diversity in picoplankton enrichment cultures: a molecular
      screening of marine isolates.
AB  - Picoplankton bacteria from a North Sea water sample were cultured under a variety
      of different conditions (nutrients, temperature, light, agitation, adhesion).
      Fluorescent in situ hybridization (FISH) analysis of the enrichments showed
      complex communities which were dominated by gamma-Proteobacteria or beta
      Proteobacteria, followed by alpha-Proteobacteria and bacteria from the
      Cytophaga/Flavobacterium/Bacteroides (CFB) cluster. Among 410 isolates, a high
      degree of diversity was found, both with respect to colony color and morphology
      and with respect to genetic diversity. Isolated bacteria were classified into the
      main taxa by a special PCR approach, termed signature PCR (SIG-PCR). It was based
      on an oligo primer mixture targeting 16S rDNA which yielded PCR products of taxon
      specific lengths. Again, gamma-Proteobacteria dominated (48%), followed by alpha
      Proteobacteria (20%). beta-Proteobacteria were rarely isolated (eight strains of
      410). The CFB cluster comprised the second largest phylum (14%), and 7.5% of all
      isolates belonged to the high-GC Gram-positives. Thus, isolated bacteria were
      representative of enrichment communities with the exception of the beta
      Proteobacteria, which were detected in high abundance in certain enrichments by
      FISH but not isolated, and the high-GC Gram-positives, which were cultivated but
      not detected by FISH. A genomic fingerprinting technique, randomly amplified
      polymorphic DNA, showed that among 58 CFB isolates only 18 identical genotypes
      were found, and among the 84 alpha-Proteobacteria only eight identical genotypes
      were present. The data show the enormous diversity of cultivated bacteria from
      picoplankton enrichment cultures of one North Sea water sample, which is only a
      small fraction of the total picoplankton community.

PMID- 11311436
TI  - Evaluation of the denitrifying microbiota of anoxic reactors.
AB  - Removal of inorganic nitrogen compounds from wastewaters can be accomplished by a
      combination of the biological processes of nitrification and denitrification. The
      information on the microbiota present in denitrifying reactors is still scarce.
      In the present work the evaluation of the denitrifying microbiota of different
      reactor sludges was performed by specific activity measurements and MPN count of
      denitrifiers. We also present the isolation and physiological and phylogenetic
      characterisation of denitrifying bacteria from the anoxic reactor of a combined
      system treating landfill leachate. Specific denitrifying activity measurements
      were faster to perform and more reliable than MPN enumerations. 16S rDNA
      characterisation of the isolates showed that they belonged to the genera Thauera,
      Acidovorax and Alcaligenes and were closely related to microorganisms retrieved
      from ecosystems rich in recalcitrant compounds. Two of the isolates could grow on
      aromatic compounds as sole carbon source.

PMID- 11311437
TI  - A molecular phylogenetic survey of sea-ice microbial communities (SIMCO).
AB  - 16S rDNA clone library analysis was used to identify bacterial biodiversity in a
      variety of sea-ice microbial communities (SIMCO). DNA was extracted from seven
      Antarctic sea-ice samples and one Arctic sea-ice sample and 16S rDNA PCR
      amplified using universal and Archaea-specific primers. Recombinant 16S rDNA
      clones were obtained and dereplicated using restriction fragment length
      polymorphism analysis (RFLP). After RFLP analysis, 100 distinct phylotypes (a
      unique clone or group of clones with sequence similarity of >0.98) were defined.
      From the clone libraries 16S rDNA sequences of bacterial and eukaryotic origin
      were detected, however Archaea were not detected either with universal or Archaea
      specific 16S rDNA primer sets. Bacterial phylotypes grouped within the alpha and
      gamma proteobacteria, the Cytophaga-Flavobacterium-Bacteroides division, the Gram
      Positive bacteria and the orders Chlamydiales and Verrucomicrobiales. The
      majority of bacterial phylotypes were affiliated with heterotrophic taxa and many
      grouped closely with cultivated genera and species. Eukaryotic clones were
      affiliated with a variety of autotrophic and heterotrophic nanoplankton and
      included a large number of chloroplast 16S rDNA genes. The findings of this
      investigation corroborated culture data indicating bacterial biodiversity
      increased in SIMCO displaying high levels of primary production, however the
      bacterial communities within SIMCO were highly heterogeneous at the genus/species
      level between different samples. A comparison of Antarctic and Arctic SIMCO
      revealed certain sea-ice dwelling bacterial genera are common at both poles.

PMID- 11311438
TI  - Stress-induced proteins of Agrobacterium tumefaciens.
AB  - The pattern of proteins produced by bacteria represents the physiological state
      of the organism as well as the environmental conditions encountered.
      Environmental stress induces the expression of several regulons encoding stress
      proteins. Extensive information about the proteins which constitute these
      regulons (or stimulons) and their control is available for very few bacteria,
      such as the Gram-positive Bacillus subtilis and the Gram-negative Escherichia
      coli (gamma-proteobacteria) and is minimal for all other bacteria. Agrobacterium
      tumefaciens is a Gram-negative plant pathogen of the alpha-proteobacteria, which
      constitutes the main tool for plant recombinant genetics. Our previous studies on
      the control of chaperone-coding operons indicated that A. tumefaciens has unique
      features and combines regulatory elements from both B. subtilis and E. coli.
      Therefore, we examined the patterns of proteins induced in A. tumefaciens by
      environmental changes using two-dimensional gel electrophoresis and dual-channel
      image analysis. Shifts to high temperature, oxidative and mild acid stresses
      stimulated the expression of 97 proteins. The results indicate that most of these
      stress-induced proteins (80/97) were specific to one stress stimulon. Only 10
      proteins appear to belong to a general stress regulon.

PMID- 11311439
TI  - Expansion of the geographic distribution of a novel lineage of epsilon
      Proteobacteria to a hydrothermal vent site on the Southern East Pacific Rise.
AB  - The diversity associated with a microbial mat sample collected from a deep-sea
      hydrothermal vent on the Southern East Pacific Rise was determined using a
      molecular phylogenetic approach based on the comparison of sequences from the
      small subunit ribosomal RNA gene (16S rDNA). The DNA was extracted from the
      sample and the 16S rDNA was amplified by PCR. Sixteen different phylotypes were
      identified by restriction fragment length polymorphism analysis; four phylotypes
      were later identified as putative chimeras. Analysis of the 16S rDNA sequences
      placed all the phylotypes within the Proteobacteria. The majority of the
      sequences (98%) were most closely related to a new clade of epsilon
      Proteobacteria that were initially identified from an in situ growth chamber
      deployed on a deep-sea hydrothermal vent on the Mid-Atlantic Ridge in 1995. The
      similarity between phylotypes identified from Atlantic and Pacific deep-sea
      hydrothermal vent sites indicates that this new clade of Proteobacteria may be
      endemic to and widely distributed among deep-sea hydrothermal vents.

PMID- 11311440
TI  - Characterisation of the culturable heterotrophic bacterial community in a small
      eutrophic lake (Priest Pot).
AB  - The community composition and structure of planktonic heterotrophic bacteria (903
      isolates) sampled from a small eutrophic lake in northern England (Priest Pot)
      was studied with respect to season (four samples) and depth (to 3.1 m). Bacteria
      (887) were isolated on tryptic soy broth agar and identified to 48 genera using
      fatty acid methyl ester analysis. The two most abundant genera isolated were
      Aeromonas and Pseudomonas which, respectively, dominated the middle to bottom
      depths in August and all depths in February. The structure of the sampled
      community was described using: species richness, Simpson's index and the Shannon
      Wiener index. All three indices detected a number of significant differences with
      depth demonstrating stratification. The greatest stratification of the bacterial
      community was observed in August when bacterial counts correlated strongly and
      negatively with diversity. Using structural measures was found to be preferable
      to the use of species frequencies in the analysis of perturbation and succession
      in community structure. Insensitivity to one or more of eight antibiotics was
      observed in 71% (61/86) of the isolates tested particularly in Gram-negative
      genera. Bacteriocinogeny and lysogeny was observed in 36% (32/90) of isolates.
      Using sensitive indicator strains, two of 10 producing strains produced virus,
      while the others produced bacteriocins.

PMID- 11311441
TI  - Isolation and phylogenetic analysis of bacteria with antimicrobial activities
      from the Mediterranean sponges Aplysina aerophoba and Aplysina cavernicola.
AB  - The aim of this study was to isolate bacteria with antimicrobial activities from
      the marine sponges Aplysina aerophoba and Aplysina cavernicola. The obtained 27
      isolates could be subdivided into eight phylogenetically different clusters based
      on comparative sequence analysis of their 16S rDNA genes. The sponge isolates
      were affiliated with the low (Bacillus) and high G+C Gram-positive bacteria
      (Arthobacter, Micrococcus), as well as the alpha-Proteobacteria (unknown isolate)
      and gamma-Proteobacteria (Vibrio, Pseudoalteromonas). One novel Bacillus species
      was identified and two species were closely related to previously uncharacterized
      strains. Isolates with antimicrobial activity were numerically most abundant in
      the genera Pseudoalteromonas and the alpha-Proteobacteria. The sponge isolates
      show antimicrobial activities against Gram-positive and Gram-negative reference
      strains but not against the fungus Candida albicans. A general pattern was
      observed in that Gram-positive bacteria inhibited Gram-positive strains while
      Gram-negative bacteria inhibited Gram-negative isolates. Antimicrobial activities
      were also found against clinical isolates, i.e. multi-resistant Staphylococcus
      aureus and Staphylococcus epidermidis strains isolated from hospital patients.
      The high recovery of strains with antimicrobial activity suggests that marine
      sponges represent an ecological niche which harbors a hitherto largely
      uncharacterized microbial diversity and, concomitantly, a yet untapped metabolic
      potential.

PMID- 11311442
TI  - Strain-specific differentiation of environmental Escherichia coli isolates via
      denaturing gradient gel electrophoresis (DGGE) analysis of the 16S-23S intergenic
      spacer region.
AB  - Denaturing gradient gel electrophoresis (DGGE) was applied to the 16S-23S rRNA
      intergenic spacer region (ISR) as a means to evaluate strain level differences in
      Escherichia coli. The ISRs of 81 environmental E. coli isolates obtained from
      bovine, poultry, and human sources yielded a total of 41 unique DGGE banding
      patterns, with identical patterns and common bands within each source and no
      overlapping patterns among sources. An additional 51 isolates from two nearby
      streams yielded 45 unique banding patterns with no overlap between sites.
      However, two of the isolates from the streams had identical banding patterns to
      those from two of the source isolates, resulting in a total of 84 unique DGGE
      banding patterns out of 132 isolates identified in this study. These results
      revealed high diversity among environmental E. coli isolates, which made it
      difficult to unambiguously ascribe strains found in water samples to specific
      host organisms.

PMID- 11311443
TI  - Changes in NMDA-receptor gene expression are associated with neurotoxicity
      induced neonatally by glutamate in the rat brain.
AB  - The N-methyl-D-aspartate receptor (NMDA-R) is fully functional in the rat early
      in embryogenesis, and diverse neuronal plasticity events are regulated through
      its activation later in postnatal development. On the other hand, systemic
      administration of glutamate (Glu) to rats at birth induces neuronal degeneration
      in glutamatergic central nervous system regions via Glu receptor activation.
      However, it is not known whether an increase in neonatal Glu levels modifies the
      gene expression of NMDA-R subunits, or if these putative changes are related to
      gamma-aminobutyric acid-mediated (GABAergic) neurotransmission. We measured, by
      means of semi-quantitative reverse transcriptase polymerase chain reaction,
      changes in gene expression of the NMDA-R subunits: NMDA-R1, NMDA-R 2A and NMDA-R
      2B in cerebral cortex (CC), striatum (ST) and hippocampus (HP) in the brains of
      rats treated neonatally with monosodium L-glutamate (MSG). These studies were
      supported by histological and quantitative analysis of the glia. Our results
      showed histological evidence of neuronal damage, and increased glial cell number
      and activity were detected. This was seen mainly in the ST and HP of MSG-treated
      animals. Significant increases in NMDA-R1, 2A and 2B subunits gene expression was
      also observed in ST and HP but not in CC, where only NMDA-R 2B was increased in
      MSG-treated rats. Our data suggest that increases in Glu levels and activation of
      Glu-receptors after neonatal administration of MSG induce an increase in glial
      cell reactivity and important changes in NMDA-R molecular composition, with signs
      of neuronal damage.

PMID- 11311444
TI  - Characterization of ceramide-induced apoptotic death in cerebellar granule cells
      in culture.
AB  - Sphingomyelin signalling system has been involved in several examples of cell
      death through apoptosis. We have characterised the effect of exposure to the cell
      permeable ceramide analogue, C2-ceramide, on cultures of differentiated
      cerebellar granule cells. C(2)-ceramide was toxic to granule cells in a dose- and
      time-dependent way at concentrations higher than 10 microM. Ceramide exposure was
      accompanied by characteristic alterations of cell morphology, namely swollen cell
      bodies and punctuate appearance and arcuate direction of processes. The final
      outcome of ceramide exposure was a form of cell death largely apoptotic in
      nature. Hoechst stain, followed by counts of nuclei with normal appearance and
      size or with condensed chromatin and reduced size, revealed a large increase of
      the proportion of shrunken nuclei in treated cultures. In situ visualisation of
      fragmented DNA through the TUNEL technique, additionally marked cells undergoing
      apoptosis as a consequence of ceramide treatment. Accordingly, the DNA extracted
      from cultures exposed to C2-ceramide and subjected to agarose gel electrophoresis
      showed the peculiar ladder of fragmented low molecular weight DNA. Treatments
      with inhibitors of two caspases or of nitric oxide synthase were unable to rescue
      neurons exposed to ceramide, thus suggesting a neurotoxic action not primarily
      dependent on activation of death proteases or on nitric oxide production.

PMID- 11311445
TI  - Effects of chronic metrifonate treatment on cholinergic enzymes and the blood
      brain barrier.
AB  - After an acute (4 h) treatment with an irreversible cholinesterase inhibitor
      organophosphate, metrifonate (100 mg/kg i.p.), the activities of both acetyl- and
      butyrylcholinesterase were inhibited (66.0-70.7% of the control level) in the rat
      brain cortex and hippocampus. There were no significant changes in the acetyl-
      and butyrylcholinesterase activities in the olfactory bulb, or in the choline
      acetyltransferase activity in all three brain areas. After chronic (2 or 5 week)
      metrifonate treatment (100 mg/kg daily i.p.), the activities of both
      cholinesterases were substantially inhibited in the rat brain cortex and
      hippocampus (15.8-31.8% of the control levels), but there was no inhibition of
      the choline acetyltransferase activity. Moreover, chronic metrifonate treatment
      did not have any effect on the distribution of the acetylcholinesterase molecular
      forms. In vitro, metrifonate proved to be a more potent inhibitor of butyryl-
      than of acetylcholinesterase in both the cortex and the hippocampus. In the
      hippocampus, the butyrylcholinesterase activity was twice as sensitive to
      metrifonate inhibition as that in the cortex (IC50 values 0.22 and 0.46 microM,
      respectively). The effects of chronic (5 week) metrifonate treatment on the blood
      brain barrier of the adult rat were examined. The damage to the blood-brain
      barrier was judged by the extravasation of Evans' blue dye in three brain
      regions: the cerebral cortex, the hippocampus, and the striatum. No extravasation
      of Evans' blue dye was found in the brain by fluorometric quantitation. These
      data indicate that chronic metrifonate treatment may increase the extracellular
      acetylcholine level via cholinesterase inhibition, but it does not have any
      effects on the blood-brain barrier. Therefore, it appears reasonable to
      hypothesize that cholinesterase activities do not play a role in the blood-brain
      barrier permeability.

PMID- 11311446
TI  - MKP-1 as a target for pharmacological manipulations in PC12 cell survival.
AB  - Dual specificity mitogen activated protein kinase phosphatase-1 (MKP-1)
      inactivates extracellular signal-regulated kinase (ERK), p38 and/or c-jun N
      terminal protein kinase (JNK) by dephosphorylation via a negative feed-back loop.
      The aim of the present study was to assess the role of expression of MKP-1 and
      phosphorylation status of mitogen-activated protein kinases (MAPKs) in promoting
      cell survival in PC12 cells. We used FK506 and three different monoperoxovanadium
      complexes (mpVs) as pharmacological tools for manipulation of MKP-1 expression.
      Peroxovanadium compounds, known to be insulinomimetic agents and protein tyrosine
      phosphatase inhibitors, are cytotoxic to the cells, they activate JNK and down
      regulate MPK-1. On the other hand, FK 506 has transient effect on ERK activation.
      However, when the agents are used in combination, ERK phosphorylation is
      prolonged and intensified, MKP-1 expression is increased, and cell survival is
      enhanced. The concomitant alterations observed in intensities and duration of
      phospho-ERKs and phospho-JNKs signals suggest that monoperoxovanadium complexes
      in combination with FK 506 enhance survival of PC12 cells by an induction of MKP
      1 expression.

PMID- 11311447
TI  - Single bout of exercise eliminates the immobilization-induced oxidative stress in
      rat brain.
AB  - We were interested in the effects of immobilization (IM), a single bout of
      exercise (E) and immobilization followed by exercise (EIM) on memory and
      oxidative damage of macromolecules in hippocampus of rat brain. Eight hours of IM
      resulted in impairment of passive avoidance test (memory retrieval deficit) and
      increased latency to start locomotion in an open-field test. Two hours of
      swimming did not significantly alter the memory retrieval deficit and latency,
      while the EIM group had longer latency and similar memory than control and E
      groups. The oxidative damage of lipids, proteins and nuclear DNA increased
      significantly in IM group and no increase was observed in E and EIM animals. The
      activity of proteasome was not altered in any groups. The activity of glutamine
      synthetase (GS) was decreased in IM group (P < 0.05), this down regulation was
      not observed in E and EIM groups. These data suggest that oxidative damage of
      macromolecules is associated with impaired cognitive function. Single bout of
      exercise after immobilization eliminates the oxidative damage of macromolecules
      and normalizes memory function, probably by its ability to restore the activity
      level of GS and eliminate the consequences of immobilization-induced prolonged
      efflux of glutamate.

PMID- 11311448
TI  - Pharmacological characterization and visualization of the glial serotonin
      transporter.
AB  - Astrocytes contain transport systems that are capable of removing various
      neurotransmitters from the synaptic cleft by transporters present in the plasma
      membrane. Glial serotonin transporter (SERT) plays an important role in the re
      uptake of 5-hydroxytryptamine (5-HT). We examined the pharmacological
      characterization of 5-HT uptake into rat cortical synaptosomes and cultured rat
      astrocytes, and the immunodetection of glial SERT proteins using specific site
      directed monoclonal antibodies (MoAb). Furthermore, using a reverse transcriptase
      polymerase chain reaction (RT-PCR) method, we addressed the expression of SERT
      mRNA in cultured rat astrocytes. We investigated the inhibitory effects of
      various monoamine uptake inhibitors on the uptake of [3H]5-HT into cultured
      astrocytes and cortical synaptosomes. Tricyclic antidepressants (clomipramine and
      imipramine) as well as selective serotonin re-uptake inhibitors (fluvoxamine,
      fluoxetine and zimelidine) were very potent inhibitors of [3H]5-HT uptake in both
      preparations. In contrast, the inhibitory effects of NE uptake inhibitors
      (nisoxetine and desipramine) and cocaine were weaker than those of 5-HT uptake
      inhibitors. In addition, dopamine (DA) uptake inhibitors (nomifensine and GBR
      12935) exhibited a Ki value in the low micromolar range. The inhibitory potencies
      were in the order 5-HT uptake inhibitors (clomipramine, fluvoxamine, fluoxetine,
      imipramine and zimelidine) > NE uptake inhibitors (nisoxetine and desipramine) =
      cocaine > DA uptake inhibitors (nomifensine and GBR-12935). There was no
      difference in the order of the inhibitory effects of various monoamine uptake
      inhibitors between the two preparations. A correlation analysis of the potencies
      of various monoamine uptake inhibitors in the inhibition of [3H]5-HT into
      cultured astrocytes and cortical synaptosomes produced a highly significant
      correlation coefficient of 0.9893 (P < 0.0001). Immunocytochemical staining using
      anti-SERT MoAb in cultured astrocytes revealed that the plasma membrane, as well
      as intracellular, perinuclear compartments, presumably endoplasmic reticulum or
      golgi membranes, showed a considerable level of immunoreactivity. Extracts of
      astrocytes and synaptosomes from the cortex were immunoblotted with anti-SERT
      MoAb. SDS-PAGE/Western blots indicate that anti-SERT MoAb recognized two bands of
      120 and 73 kDa in both preparations. RT-PCR demonstrated that astrocytes in
      cultured expressed mRNA for the cloned SERT protein, which has been characterized
      as the neuronal SERT. These pharmacological experiments indicate that this uptake
      process takes place through glial SERT that is very similar to neuronal SERT.
      Furthermore, the present data also indicate that the presence of the mRNA and
      protein for the neuronal SERT were established in cultured rat astrocytes, and
      the polypeptide portion of SERT in astrocytes and frontal cortex could be the
      same gene product.

PMID- 11311449
TI  - In vitro tolerance to inhibition by ethanol of N-methyl-D-aspartate-induced
      depolarization in locus coeruleus neurons of behaviorally ethanol-tolerant rats.
AB  - Intracellular recordings were made in pontine slice preparations of the rat brain
      containing the locus coeruleus (LC). Ethanol at 100 mM, but not at 10 or 30 mM
      inhibited depolarizing responses to pressure-applied N-methyl-D-aspartate (NMDA)
      in LC neurons of ethanol-naive rats. Ethanol (100 mM) had a similar effect in LC
      neurons of ethanol-naive rats, of rats treated with ethanol for 14 days (3 g/kg
      daily, i.p.) and of rats treated with equicaloric amounts of saccharose (5 g/kg
      daily, i.p.). The blood concentration of ethanol was markedly decreased at 4 h,
      and was below the detection limit at 24 h after the last injection. Behavioral
      measurements in the open-field system demonstrated the development of tolerance
      in rats receiving ethanol for 14 days. Moreover, an anxiety-related reaction was
      shown to develop when the acute effect of the last ethanol injection vanished.
      Therefore, in subsequent in vitro experiments, ethanol (10 mM) was continuously
      present in the superfusion medium in order to mimic a steady blood concentration
      and to prevent a withdrawal-like situation. Under these conditions, ethanol (100
      mM) still continued to inhibit the NMDA-induced depolarization in slices of
      untreated rats, but became ineffective in slices of ethanol-treated rats at 4 h
      after the last injection. By contrast, a supersensitivity to ethanol developed in
      brain slices at 24 h after the last ethanol injection. In conclusion, in vitro
      tolerance between systemically and locally applied ethanol at LC neurons could
      only be demonstrated when a low concentration of ethanol was added to the
      superfusion medium to simulate the blood concentration of this compound.

PMID- 11311450
TI  - Excessive release of [3H] noradrenaline by veratridine and ischemia in spinal
      cord.
AB  - In this study, the properties of ischemic condition-induced and veratridine
      evoked [3H]noradrenaline ([3H]NA) release from rat spinal cord slices were
      compared. It was expected that ischemia mimicked by oxygen and glucose
      deprivation results in the impairment of Na+/K+ -ATPase with a consequent
      elevation of the intracellular Na+ -level which reverses the NA carrier and
      promotes excessive NA release, and veratridine, by the activation of Na+
      channels, releases NA both carrier-mediated and Ca2+ -dependent, i.e. vesicular
      manner. In our experiments, veratridine (1-100 microM) dose-dependently increased
      the resting [3H]NA release, and its effect was only partially blocked by low
      temperature or the lack of external calcium, whereas the sodium channel inhibitor
      tetrodotoxin (TTX, 1 microM) completely prevented it, indicating that veratridine
      induces NA release via axonal depolarization and reversing the transporters by
      eliciting Na+ -influx. In contrast to TTX, the local anesthetic lidocaine (100
      microM) only partially blocked the veratridine-induced [3H]NA release due to its
      inhibitory action on K+ channels. The ischemia-induced [3H]NA release was
      abolished at 12 degrees C, a temperature known to block only the transporter
      mediated release of transmitters. However, lidocaine was also partially effective
      to reverse the action of ischemia on the NA release, indicating that lidocaine is
      not a useful compound in the treatment of spinal cord-injured patients against
      the excessive excytotoxic NA release.

PMID- 11311451
TI  - Extracellular glutamate changes in rat striatum during ischemia determined by a
      novel dialysis electrode and conventional microdialysis.
AB  - Our newly developed method using a dialysis electrode has made it possible to
      perform real time monitoring of extracellular glutamate concentration ([Glu]e)
      utilizing the oxygen-independent reaction with glutamate oxidase and ferrocene.
      In this study, we therefore, investigated [Glu]e changes during brain ischemia
      using both the conventional microdialysis method and the dialysis electrode
      method. A comparison between our newly developed dialysis electrode and
      conventional microdialysis methods provided the following results. When the
      conventional microdialysis method was employed: (1) the elevation of [Glu]e
      during complete global ischemia was delayed; and (2) the elevation of
      concentration and reuptake of glutamate were delayed during 10-min transient
      ischemia, and the elevation of [Glu]e reached a maximum later using conventional
      microdialysis than using our dialysis electrode. (3) The biphasic [Glu]e
      elevation of glutamate concentration detected using the dialysis electrode method
      was not observed using the conventional microdialysis method. It was additionally
      investigated why the conventional microdialysis method provides inferior time
      resolution. In this study, we also demonstrated with the chromatographic SMART
      procedure coupled to UV detection that biogenic substances, i.e. low molecular
      weight proteins and peptides, are released during ischemic injury, and they may
      cause a delay in the time resolution in the microdialysis method.

PMID- 11311452
TI  - Release of D,L-threo-beta-hydroxyaspartate as a false transmitter from excitatory
      amino acid-releasing nerve terminals.
AB  - This study examined whether preaccumulated D,L-threo-beta-hydroxyaspartate (tHA),
      a competitive substrate for the high-affinity excitatory amino acid (EAA)
      transporter, is released as a false transmitter from EAA-releasing nerve
      terminals. Potassium-stimulation (50 mM for 1 min) evoked significant release of
      the endogenous EAAs (aspartate and glutamate) from superfused neocortical
      minislices. Endogenous EAA release was largely calcium-dependent and was
      inhibited by tetanus toxin, a neurotoxin which specifically blocks vesicular
      exocytosis. In parallel experiments, minislices were pre-incubated with 500
      microM tHA. Potassium (50 mM) evoked significant release of tHA and this release
      was also calcium-dependent and reduced by tetanus toxin. Pre-accumulation of tHA
      did not affect the release of endogenous glutamate whereas the release of
      endogenous aspartate was significantly attenuated. These data suggest that tHA
      selectively accumulates in a vesicular aspartate pool and is released upon
      depolarization as a false transmitter from EAA nerve terminals.

PMID- 11311453
TI  - Thiabendazole induces urinary tract toxicity in male ICR mice.
AB  - Male ICR mice were administered thiabendazole (TBZ) in the diet at concentration
      of 0 (control), 0.8, 1.2 and 1.6% for 44 weeks. The mortality was 10, 6, 40 or
      90% in control, 0.8, 1.2 or 1.6% TBZ group, respectively. In dead mice, the gross
      findings included the abnormalities of kidney such as atrophy, hydronephrosis or
      swelling in 2, 67, 95 or 96% of the 0, 0.8, 1.2 or 1.6% TBZ group, respectively.
      In surviving mice at the end of study, the right kidney weight of treated groups
      was significantly lower than that of control group. The urinary bladder weight of
      treated groups was significantly higher than that of control group. Gross
      findings in treated mice included the renal atrophy, hydronephrosis, calculi in
      renal pelvis or urinary bladder and thickening of the bladder wall. Microscopic
      findings in the kidneys of treated mice included nephrosis, hydronephrosis and
      hyperplasia of transitional epithelium of renal pelvis and/or papilla. In the
      urinary bladder, hyperplasia or squamous metaplasia of transitional epithelium
      were found in treated mice. Administration of TBZ in the diet for 44 weeks
      results in nephrosis and calculus formation in the renal pelvis and urinary
      bladder of male ICR mice, and is associated with hyperplasia of transitional
      epithelium of renal pelvis or urinary bladder.

PMID- 11311454
TI  - Abnormal auditory brainstem responses for mice treated with mercurial compounds:
      involvement of excessive nitric oxide.
AB  - In this paper, we attempted to construct an animal (mouse) model for monitoring
      the oto-neurotoxicity of mercuric sulfide, comparing its toxicity with the well
      known (organic) mercury compound methyl-mercury. Mice were treated with either
      mercuric sulfide (HgS, 0.1 and 1.0 g/kg per day) or methyl-mercury (MeHg, 0.2,
      2.0 and 10 mg/kg per day) by gastric gavage for 7 consecutive days. Analysis of
      auditory brainstem response (ABR) indicated that significant elevation of the
      physiological hearing threshold as well as significant prolongation of interwave
      latency I-V was observed for MeHg -- (2.0 and 0.2 mg/kg per day) or HgS -- (1.0
      g/kg per day, but not 0.1 g/kg per day) treated mice. Further, both MeHg- and HgS
      treated animals demonstrated a significant prolongation of interwave latency I-V
      that increased with an increasing mean blood-Hg level. The oto-neurotoxicity of
      MeHg (2.0 mg/kg per day) persisted to at least 11 weeks subsequent to the
      cessation of its administration. The toxic effect of HgS, however, disappeared
      completely 5 weeks subsequent to the cessation of its administration. These
      results suggest a correlation between the Hg-elicited hearing dysfunction and the
      availability of mercury in brain tissue. Both inhibition of Na(+)/K(+)-ATPase
      activity and overproduction of nitric oxide in the brainstem are consistent with
      an analysis of the physiological hearing threshold and latencies of ABR waveform
      at all time points throughout the experimental process. Thus, it is proposed that
      high-dose HgS or MeHg intoxication is associated with a decrease in functional
      Na(+)/K(+)-ATPase activity in the brainstem of affected animals, this presumably
      arising via excessive nitric oxide production, and suggesting that brainstem
      damage may play a role in mercury-induced hearing loss.

PMID- 11311455
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on fetal mouse urinary
      tract epithelium in vitro.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), produces hydronephrosis by altering
      the differentiation and proliferation of ureteric epithelial cells in the fetal
      C57BL/6N mouse urinary tract. This study tests the hypothesis that the late fetal
      urinary tract epithelial cells respond to TCDD with increased proliferation and
      that the responses do not require contributions from other maternal or fetal
      tissues. This was achieved by exposing late gestation fetal urinary tract cells
      to TCDD in an in vitro model. Isolated ureteric cells from gestation day (GD) 18
      fetal ureters were plated in medium supplemented with trace elements, a complex
      mixture of lipids, a defined mixture of purified hormones and growth factors.
      Both epithelial and mesenchymal cells remain viable under these conditions. The
      cultures were exposed to 0.1% dimethylsulfoxide (DMSO), 1x10(-8), 1x10(-9) or
      1x10(-10) M TCDD. Exposure to 1x10(-10) M TCDD did not affect the cultures, while
      1x10(-8) and 1x10(-9) M TCDD supported epithelial, but not mesenchymal, cell
      survival and stimulated epithelial cell proliferation and differentiation. The
      TCDD-exposed cells expressed high levels of keratin and little or no vimentin,
      confirming that the cells, which survive and differentiate are epithelial.
      However, after continuous exposure to epidermal growth factor (EGF), the TCDD
      induced stimulation of ureteric epithelial growth could not be detected. In
      conclusion, this study demonstrates that late gestational ureteric cells respond
      to TCDD in vitro with the stimulation of epithelial cell growth and
      differentiation.

PMID- 11311456
TI  - Acute exposure to trichloroethylene differentially alters the susceptibility to
      chemoconvulsants in mice.
AB  - The effects of a common industrial solvent, trichloroethylene (TCE), which was
      once used as an anesthetic agent but its in vivo mechanism is still unknown, on
      convulsant-induced seizures in mice were examined. Pretreatment with TCE (250
      2000 mg/kg, i.p.) significantly increased pentylenetetrazol (PTZ)-, picrotoxin
      (PIC)-, bicuculline (BIC)-, strychnine (STY)-, 4-aminopyridine (4-AP)- and N
      methyl-D-aspartate (NMDA)-induced convulsion thresholds and lethal doses.
      However, the increase in convulsion thresholds and lethal doses was much greater
      for GABAergic antagonists (PIC, BIC, and PTZ) than non-GABAergic convulsants
      (STY, 4AP, and NMDA) following 2000 mg/kg TCE administration. Pre-treatment of
      mice with disulfiram (an inhibitor of CYP 4502E1) but not 4-methyl pyrazole (an
      inhibitor of alcohol dehydrogenase) significantly prolonged the time required for
      TCE (5000 mg/kg, i.p.) to induce the loss of righting reflex. These results
      suggest that acute exposure to TCE differentially alters the susceptibility to
      chemically induced convulsions in mice. The anticonvulsive effect of TCE may be
      predominantly mediated by GABA(A) receptors. In addition, TCE appears to exert a
      direct anesthetic effect.

PMID- 11311457
TI  - Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen
      metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
AB  - The bioactivation of N-nitrosamines and polycyclic aromatic hydrocarbons (PAHs)
      is mediated primarily by the mixed-function oxidase system, which includes
      dimethylnitrosamine N-demethylase I, arylhydrocarbon [benzo(a)pyerne]
      hydroxylase, cytochrome P450, cytochrome b(5), and ethoxycoumarin deethylase.
      Most of carcinogens and xenobiotics are conjugated and detoxified by phase II
      drug-metabolizing enzymes such as glutathione S-transferase. The present study
      showed the influence of Schistosoma haematobium on the activity of the above
      mentioned enzymes in 13 schistosome-infected human bladder tissues compared with
      those of 15 schistosome-free samples. The contents of cytochrome P450 and
      cytochrome b(5) were increased in the bladder tissues by 48 and 69%,
      respectively. Moreover, the activities of dimethylnitrosamine N-demethylase I and
      arylhydrocarbon hydroxylase, ethoxycoumarin O-deethylase, ethoxyresourfin O
      deethylase, and pentoxyresorufin O-pentoxyresorufin were increased by 75, 159,
      49, 63 and 44%, respectively. The signal intensity for cytochrome P450 2E1 was
      greatly increased over the control. Also, the activity of glutathione S
      transferase was increased by 89%. On the other hand, the activity of glutathione
      reductase and the level of reduced glutathione were decreased by 40 and 57%,
      respectively. Interestingly, the level of free radical, thiobarbituric acid
      reactive substance, was increased in the schistosome-infected human bladder
      tissues by 125%. The present study clearly demonstrated that S. haematobium
      changes the activity of carcinogen-metabolizing enzymes. We conclude that S.
      haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons
      (e.g. benzo(a)pyrene) and N-nitrosamines (e.g. dimethylnitrosamine) through
      induction of their corresponding bioactivating enzymes in human bladder tissues.

PMID- 11311458
TI  - Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention.
AB  - Agranulocytosis is a rare, severe and unpredictable idiosyncratic reaction
      associated with drug therapy that can lead to life-threatening illness.
      Typically, the patient presents with a fever and evidence of infection 1-3 months
      after initiation of drug administration with a neutrophil count below 0.5x10(9)
      l. Of the drugs linked with this disease, aminopyrine, dipyrone, clozapine, anti
      thyroid agents, sulphonamides and dapsone are the best documented. Generally,
      agranulocytosis is associated with older individuals (>60 years) and those of non
      Caucasian descent. The incidence of agranulocytosis in subjects taking oral
      dapsone in combination with maloprim for malaria is 1 -- 10-20,000 while leprosy
      patients treated with dapsone exhibit virtually zero risk of agranulocytosis.
      However, dapsone is unusual in that during the rare but severe inflammatory
      disease, dermatitis herpetiformis (DH), the risk of agranulocytosis is multiplied
      between 25 and 33 fold compared with normal patients. It is conceivable that
      dapsone might exhibit a similar risk in coeliac disease, a condition related to
      DH. As dapsone plasma levels in DH subjects can be high (2-10 microg/ml) the
      increased risk of agranulocytosis could be related to drug dosage, or increased
      immune responsiveness. The high risks in DH patients probably necessitate
      monitoring of neutrophil cell population in the first 3 months of therapy, while
      topical usage of the drug in acne treatment in otherwise healthy patients
      predominantly below the age of 25 is at the opposite end of the risk scale,
      probably as low as 1 in 10-20,000 patients.

PMID- 11311459
TI  - Lead treatment in vitro at early developmental stage of bone marrow-derived
      macrophages enhances NO production through IL-1beta and IL-6 but not TNF-alpha.
AB  - Lead (Pb(2+)) is known to decrease or block nitric oxide (NO) production by
      mature macrophages (mphi). Bone marrow cells were treated with various doses of
      lead in vitro and the morphological and functional changes were observed. Bone
      marrow cells were treated with various doses of lead (1, 10, 20 and 50 microM) at
      the start of culture with mphi growth factor (CSF-1), and after 6-7 days of
      culture, the resultant mphi (bone marrow-derived mphi, BMDM) showed decreased NO
      production. Unexpectedly, BMDM from the lowest does of lead treatment (1.0
      microM) showed increased NO production. The increased NO production was due to
      increased expression of the iNOS gene and concurrent enhanced transcript levels
      of proinflammatory cytokines such as IL-1beta and IL-6, but not TNF-alpha. Lead
      treatment on mature BMDM showed decreased NO production in a dose-dependent
      manner. These results suggest that a low dose of lead affects developmental
      characteristics of BMDM through different proinflammatory cytokines, and the lead
      effects on precursor cells of mphi and mature mphi are different.

PMID- 11311461
TI  - Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors
      and retrograde messengers in rat brainstem slices.
AB  - The analysis of cellular-molecular events mediating synaptic plasticity within
      vestibular nuclei is an attempt to explain the mechanisms underlying vestibular
      plasticity phenomena. The present review is meant to illustrate the main results,
      obtained in vitro, on the mechanisms underlying long-term changes in synaptic
      strength within the medial vestibular nuclei. The synaptic plasticity phenomena
      taking place at the level of vestibular nuclei could be useful for adapting and
      consolidating the efficacy of vestibular neuron responsiveness to environmental
      requirements, as during visuo-vestibular recalibration and vestibular
      compensation. Following a general introduction on the most salient features of
      vestibular compensation and visuo-vestibular adaptation, which are two plastic
      events involving neuronal circuitry within the medial vestibular nuclei, the
      second and third sections describe the results from rat brainstem slice studies,
      demonstrating the possibility to induce long-term potentiation and depression in
      the medial vestibular nuclei, following high frequency stimulation of the primary
      vestibular afferents. In particular the mechanisms sustaining the induction and
      expression of vestibular long-term potentiation and depression, such as the role
      of various glutamate receptors and retrograde messengers have been described. The
      relevant role of the interaction between the platelet-activating factor, acting
      as a retrograde messenger, and the presynaptic metabotropic glutamate receptors,
      in determining the full expression of vestibular long-term potentiation is also
      underlined. In addition, the mechanisms involved in vestibular long-term
      potentiation have been compared with those leading to long-term potentiation in
      the hippocampus to emphasize the most significant differences emerging from
      vestibular studies. The fourth part, describes recent results demonstrating the
      essential role of nitric oxide, another retrograde messenger, in the induction of
      vestibular potentiation. Finally the fifth part suggests the possible functional
      significance of different action times of the two retrograde messengers and
      metabotropic glutamate receptors, which are involved in mediating the presynaptic
      mechanism sustaining vestibular long-term potentiation.

PMID- 11311462
TI  - N-methyl-D-aspartate channel and consciousness: from signal coincidence detection
      to quantum computing.
AB  - Research on Blindsight, Neglect/Extinction and Phantom limb syndromes, as well as
      electrical measurements of mammalian brain activity, have suggested the
      dependence of vivid perception on both incoming sensory information at primary
      sensory cortex and reentrant information from associative cortex. Coherence
      between incoming and reentrant signals seems to be a necessary condition for
      (conscious) perception. General reticular activating system and local electrical
      synchronization are some of the tools used by the brain to establish coarse
      coherence at the sensory cortex, upon which biochemical processes are
      coordinated. Besides electrical synchrony and chemical modulation at the synapse,
      a central mechanism supporting such a coherence is the N-methyl-D-aspartate
      channel, working as a 'coincidence detector' for an incoming signal causing the
      depolarization necessary to remove Mg(2+), and reentrant information releasing
      the glutamate that finally prompts Ca(2+) entry. We propose that a signal
      transduction pathway activated by Ca(2+) entry into cortical neurons is in charge
      of triggering a quantum computational process that accelerates inter-neuronal
      communication, thus solving systemic conflict and supporting the unity of
      consciousness.

PMID- 11311463
TI  - Cerebral microvascular pathology in aging and Alzheimer's disease.
AB  - The aging of the central nervous system and the development of incapacitating
      neurological diseases like Alzheimer's disease (AD) are generally associated with
      a wide range of histological and pathophysiological changes eventually leading to
      a compromised cognitive status. Although the diverse triggers of the
      neurodegenerative processes and their interactions are still the topic of
      extensive debate, the possible contribution of cerebrovascular deficiencies has
      been vigorously promoted in recent years. Various forms of cerebrovascular
      insufficiency such as reduced blood supply to the brain or disrupted
      microvascular integrity in cortical regions may occupy an initiating or
      intermediate position in the chain of events ending with cognitive failure. When,
      for example, vasoconstriction takes over a dominating role in the cerebral
      vessels, the perfusion rate of the brain can considerably decrease causing
      directly or through structural vascular damage a drop in cerebral glucose
      utilization. Consequently, cerebral metabolism can suffer a setback leading to
      neuronal damage and a concomitant suboptimal cognitive capacity. The present
      review focuses on the microvascular aspects of neurodegenerative processes in
      aging and AD with special attention to cerebral blood flow, neural metabolic
      changes and the abnormalities in microvascular ultrastructure. In this context, a
      few of the specific triggers leading to the prominent cerebrovascular pathology,
      as well as the potential neurological outcome of the compromised cerebral
      microvascular system are also going to be touched upon to a certain extent,
      without aiming at total comprehensiveness. Finally, a set of animal models are
      going to be presented that are frequently used to uncover the functional
      relationship between cerebrovascular factors and the damage to neural networks.

PMID- 11311464
TI  - Cauda equina syndrome.
AB  - Single or double-level compression of the lumbosacral nerve roots located in the
      dural sac results in a polyradicular symptomatology clinically diagnosed as cauda
      equina syndrome. The cauda equina nerve roots provide the sensory and motor
      innervation of most of the lower extremities, the pelvic floor and the
      sphincters. Therefore, in a fully developed cauda equina syndrome, multiple signs
      of sensory disorders may appear. These disorders include low-back pain, saddle
      anesthesia, bilateral sciatica, then motor weakness of the lower extremities or
      chronic paraplegia and, bladder dysfunction. Multiple etiologies can cause the
      cauda equina syndrome. Among them, non-neoplastic compressive etiologies such as
      herniated lumbosacral discs and spinal stenosis and spinal neoplasms play a
      significant role in the development of the cauda equina syndrome. Non-compressive
      etiologies of the cauda equina syndrome include ischemic insults, inflammatory
      conditions, spinal arachnoiditis and other infectious etiologies. The use of
      canine, porcine and rat models mimicking the cauda equina syndrome enabled
      discovery of the effects of the compression on nerve root neural and vascular
      anatomy, the impairment of impulse propagation and the changes of the
      neurotransmitters in the spinal cord after compression of cauda equina. The
      involvement of intrinsic spinal cord neurons in the compression-induced cauda
      equina syndrome includes anterograde, retrograde and transneuronal degeneration
      in the lumbosacral segments. Prominent changes of NADPH diaphorase exhibiting,
      Fos-like immunoreactive and heat shock protein HSP72 were detected in the
      lumbosacral segments in a short-and long-lasting compression of the cauda equina
      in the dog. Developments in the diagnosis and treatment of patients with back
      pain, sciatica and with a herniated lumbar disc are mentioned, including many
      treatment options available.

PMID- 11311465
TI  - From cells to computers: computing with membranes (P systems).
AB  - The aim of this paper is to introduce to the reader the main ideas of computing
      with membranes, a recent branch of (theoretical) molecular computing. In short,
      in a cell-like system, multisets of objects evolve according to given rules in
      the compartments defined by a membrane structure and compute natural numbers as
      the result of halting sequences of transitions. The model is parallel,
      nondeterministic. Many variants have already been considered and many problems
      about them were investigated. We present here some of these variants, focusing on
      two central classes of results: (1) characterizations of the recursively
      enumerable sets of numbers and (2) possibilities to solve NP-complete problems in
      polynomial--even linear--time (of course, by making use of an exponential space).
      The results are given without proofs. An almost complete bibliography of the
      domain, at the middle of October 2000, is also provided.

PMID- 11311466
TI  - Modelling of hexadecane degradation in continuous-flow cultures.
AB  - Microorganisms of Wadden Sea sediments are able to degrade hydrocarbons in
      suspensions. (Berthe-Corti, L., Bruns, A., Hulsch, R., 1997. J. Microb. Methods
      29, 129-137) have observed in continuous culture experiments that the growth rate
      of microorganisms increases roughly proportional to the dilution rate. The growth
      rate is nearly independent of the oxygen saturation down to about 0.5%. Even at
      very low oxygen supply, corresponding to an oxygen saturation far below 0.1%,
      growth takes place at a reduced rate. In this paper, a model is presented which
      can reproduce the results of these experiments. The model treats the following
      processes, selection of the active fraction of microorganisms growing on
      hexadecane, uptake of hexadecane and transformation into palmitate as a first
      metabolic step, synthesis of biomass, respiration and exudation. The processes
      are regulated by the substrate concentration, the internal palmitate quota, the
      exudates' concentration and an inhibiting factor. For the experiments under very
      low oxygen conditions, the observed growth with reduced O(2)-consumption and
      CO(2)-production is modelled by assuming an anoxic metabolic pathway.

PMID- 11311467
TI  - Rhythmic and non-rhythmic attractors in asynchronous random Boolean networks.
AB  - In multi-component, discrete systems, such as Boolean networks and cellular
      automata, the scheme of updating of the individual elements plays a crucial role
      in determining their dynamic properties and their suitability as models of
      complex phenomena. Many interesting properties of these systems rely heavily on
      the use of synchronous updating of the individual elements. Considerations of
      parsimony have motivated the claim that, if the natural systems being modelled
      lack any clear evidence of synchronously driven elements, then random
      asynchronous updating should be used by default. The introduction of a random
      element precludes the possibility of strictly cyclic behaviour. In principle,
      this poses the question of whether asynchronously driven Boolean networks,
      cellular automata, etc., are inherently bad choices at the time of modelling
      rhythmic phenomena. This paper focuses on this subsidiary issue for the case of
      Asynchronous Random Boolean Networks (ARBNs). It defines measures of pseudo
      periodicity between states and sufficiently relaxed statistical constraints.
      These measures are used to guide a genetic algorithm to find appropriate
      examples. Success in this search for a number of cases, and the subsequent
      statistical analysis lead to the conclusion that ARBNs can indeed be used as
      models of co-ordinated rhythmic phenomena, which may be stronger precisely
      because of their in-built asynchrony. The same technique is used to find non
      stationary attractors that show no rhythm. Evidence suggests that the latter are
      more abundant than rhythmic attractor. The methodology is flexible, and allows
      for more demanding statistical conditions for defining pseudo-periodicity, and
      constraining the evolutionary search.

PMID- 11311468
TI  - Time course equations of the amount of substance in a linear compartmental system
      and their computerized derivation.
AB  - In this contribution, we present the symbolic time course equations corresponding
      to a general model of a linear compartmental system, closed or open, with or
      without traps and with zero input. The steady state equations are obtained easily
      from the transient phase equations by setting the time --> infinity. Special
      attention has been given to the open systems, for which an exhaustive kinetic
      analysis has been developed to obtain important properties. Besides, the results
      have been particularized to open systems without traps and an alternative
      expression for the distribution function of exit times has been provided. We have
      implemented a versatile computer program, that is easy to use and with a user
      friendly format of the input of data and the output of results. This computer
      program allows the user to obtain all the information necessary to derive the
      symbolic time course equations for closed or open systems as well as for the
      derivation of the distribution function of exit times.

PMID- 11311469
TI  - Diagnostic criteria for multiple sclerosis.
AB  - Over a hundred years ago, Charcot set down what he considered to be some of the
      clinical characteristics of multiple sclerosis (MS). His triad was not specific
      but it was the first attempt to separate this disease from the many others
      affecting the nervous system. The history of clinical diagnostic criteria
      demonstrates the evolution from rather tentative classifications of restricted
      value to the more elaborate 1983 scheme which incorporates some laboratory
      procedures under the rubric paraclinical tests, considered to be extensions of
      the neurological examination, as well as a new category based on the presence of
      specific abnormalities of the cerebrospinal fluid (CSF). It is curious that until
      then the term definite MS had been avoided except for autopsy-proven cases,
      perhaps a wise move, since exact diagnosis may require long term observation. All
      the proposed schemes have been based on the twin principles of dissemination in
      both time and space. The diagnosis of MS must remain a clinical one, supported
      but not supplanted by the increasingly popular magnetic resonance imaging, which
      is non-specific and is frequently overinterpreted by radiologists lacking
      appropriate clinical information. Reliance on the MRI as the principal if not
      exclusive basis for the diagnosis leads to error in as many as one third of
      cases. This assumes a great deal of importance considering that such non-MS
      patients may be counted in epidemiological surveys and included in therapeutic
      trials for disease-modifying drugs, or eventually treated with these very
      expensive drugs with still controversial long term efficacy. Not surprisingly,
      attempts to develop reliable criteria for the MRI diagnosis of MS have been
      unsuccessful in view of the lack of specificity of that procedure. Great care
      should be taken to exclude the presence of extrinsic cervical spine lesions which
      might impinge on the cord, leading to the formation of plaques, or mimic the
      course of MS. An MRI of the cervical spine is recommended in all patients
      suspected of having MS who have symptoms suggestive of spinal cord involvement.
      The diagnosis of MS is, and will remain, based on clinical criteria which codify
      the characteristic dissemination in time and space of MS.

PMID- 11311470
TI  - Involvement of disregulated c-myc but not c-sis/PDGF in atypical and anaplastic
      meningiomas.
AB  - We investigated the expression of c-myc and c-sis/PDGF mRNA and protein products
      in 20 cases of meningiomas of various grades: 10 benign, 5 atypical and 5
      anaplastic meningiomas. All cases of atypical and anaplastic meningiomas were
      positive for c-myc protein and mRNA by immunohistochemistry and in situ
      hybridisation, respectively, while all 10 benign meningiomas were negative for c
      myc immunostaining, with only one benign tumour positive for c-myc mRNA.
      Expression of PDGF-BB protein and c-sis mRNA were seen in more than 80% of the
      meningioma cases and was not restricted to the histological grades of
      meningiomas. Semiquantitative analysis showed that the frequency of c-myc
      immunopositive cells positively correlated with Ki-67 proliferative indices. Our
      findings suggest that c-myc, but not c-sis/PDGF, has some concern to the
      malignancy of meningiomas.

PMID- 11311471
TI  - Perforating branches of the anomalous anterior communicating complex.
AB  - The anterior communicating complex was studied in 25 cadaver specimens obtained
      at routine autopsy. In 15 specimens (60%), an anomalous anterior communicating
      artery was found. The most common anomaly identified was a multi-channeled
      anterior communicating artery. The first channel was always the smallest channel,
      and all of the perforators arose from this smallest channel 45% of the time. All
      other anomalous anterior communicating arteries presented with concomitant
      anomalous perforator anatomy.

PMID- 11311472
TI  - Results of surgical treatment of intrasylvian hematomas due to ruptured
      intracranial aneurysms.
AB  - In this retrospective study, the surgical outcome of patients with intrasylvian
      hematomas due to rupture of intracranial aneurysms was analyzed. The authors
      studied ten patients who underwent aneurysm surgery and evacuation of the
      hematoma within 12 h of the onset of bleeding. All patients had an intrasylvian
      hematoma classified with computerized tomography and all patients underwent pre
      operative angiography. In all patients, the origin of bleeding was a middle
      cerebral artery aneurysm, with the exception of one patient whose bleeding
      originated from a posterior communicating artery aneurysm. Three patients
      achieved good recovery without any significant neurological deficit and four
      achieved good recovery with moderate disabilities. One patient died due to
      pneumonia and two were in a vegetative state. Notably, three patients who were
      comatose (Hunt and Hess Grade V) at the time of presentation achieved good
      recovery following surgery. In this study, neurological status at presentation
      did not predict the outcome. The only significant prognostic factor in those
      patients who had intrasylvian hematoma was early surgery within 12 h of the
      bleeding. We suggest that early surgical treatment be performed in patients with
      intrasylvian hematoma, regardless of the neurological findings and grade on
      admission. Pre-operative angiography seems to be essential in identifying the
      source of bleeding.

PMID- 11311473
TI  - Treatment-induced neoangiogenesis in cerebral arteriovenous malformations.
AB  - We investigated the angiogenetic and proliferative activity of the endothelium of
      30 consecutive surgical cases of AVM treated at our institution by
      immunohistochemical detection of the PCNA, MIB-1, Flk-1 and VEGF antibodies.
      Endothelial positive immunostaining was observed in 87% of the cases for PCNA, in
      20% for MIB-1, and in 80% for Flk-1. Of 22 individuals treated with incomplete
      embolization prior to surgery, 17 showed an expression of VEGF (77%), but only
      two of the eight patients (25%) who were treated without prior embolization
      exhibited such an immunoreaction (P=0.0086). The proliferation and growth of
      cerebral AVMs is documented by endothelial expression of PCNA and MIB-1. The
      statistically significantly higher expression of VEGF in partially obliterated
      (embolized) AVMs is most likely caused by transient regional hypoxia within the
      AVM nidus that mediates neoangiogensis. It points out the clinical relevance of a
      complete occlusion in order to avoid neovascularization associated with
      subsequent morbidity and mortality.

PMID- 11311474
TI  - Benign intracranial hypertension: correlation of cerebral blood flow with disease
      severity.
AB  - Benign intracranial hypertension (BIH) is characterized by symptoms and signs of
      raised intracranial pressure in the absence of an intracranial mass lesion,
      infection or hydrocephalus. The purpose of this study was to evaluate the effect
      of disease severity on cerebral blood flow in patients with BIH on acetazolamide
      therapy. METHODS: 11 patients (nine females, two males; mean age 30.5 years;
      range 22-29 years) with BIH were studied. All patients underwent CT and MRI
      scanning which were normal. The CSF pressure of all patients was above 200 mm
      H2O. All patients were under treatment with acetazolamide (1 g/day). Disease
      severity was determined by visual field examination and by clinical symptoms.
      Five patients were categorized into mild to moderate BIH (group I) and six
      patients had severe BIH (group II). All patients underwent perfusion brain SPECT
      with 740 MBq of Tc-99m-HMPAO. RESULTS: Brain perfusion abnormalities were
      observed in six of the 11 patients. One out of five patients in group I (20%) and
      five out of six patients (83%) in group II, had abnormal SPECT findings (P<0.04).
      In four patients of group II the left parietal lobe was involved and another
      patient had a right occipital abnormality. The single patient from group I with
      SPECT abnormalities demonstrated focal decreased perfusion in the left temporal
      area and decreased perfusion in the left caudate nucleus. CONCLUSION: Patients
      with severe degree of BIH have a higher incidence of cerebral perfusion
      abnormalities. This group may have an increased risk of cerebrovascular
      complications. The continuous administration of acetazolamide which affects the
      vascular autoreactivity may contribute to the regional hypoperfusion. Further
      studies are recommended to evaluate the natural course of disease versus
      iatrogenic treatment effects.

PMID- 11311475
TI  - Fatal cerebral embolism in a young patient with an occult left atrial myxoma.
AB  - We report a young patient with a fatal cerebral embolism from an occult atrial
      myxoma. The patient died before echocardiography was performed and at autopsy the
      definite diagnosis was made. Our patient suffered from migraine of increasing
      frequency. The physical exercise of sexual intercourse was the precipitating
      factor of this fatal embolism. The importance of early echocardiography is
      stressed, especially in view of the recent tendency of early and aggressive
      stroke treatment.

PMID- 11311476
TI  - Cervical intramedullar schistosomiasis as a rare cause of acute tetraparesis.
AB  - INTRODUCTION: The trematode infection schistosomiasis affects at least 200
      million people in endemic areas. Granulomas cause the typical manifestations of
      urogenital, intestinal and hepatolienal schistosomiasis. Involvement of other
      organs especially the central nervous system (CNS) is uncommon. CASE REPORT: We
      describe a 40-year old male with a history of repeated contact with schistosome
      contaminated water. After having suffered from flu-like symptoms with fever and
      arthralgias, he first presented with a polyradiculopathy of unknown origin. Then
      4 weeks later an acute tetraparesis occurred. Spinal magnetic resonance imaging
      (MRI) revealed a spinal stenosis and query medullary hyperintensities at C6-C8
      without contrast-enhancement. Serologic testing was positive for schistosomiasis.
      The intraoperative appearance at decompressive laminectomy revealed a myelitic
      form of schistosomiasis. Under therapy with praziquantel, initially high dose
      cortisone and intensive physiotherapy, symptoms slowly improved over months. On
      follow-up 1 year later, the patient presented with a spastic distally marked
      tetraparesis and sensory impairment from C6 downwards. CONCLUSION: Cervical
      intramedullar schistosomiasis is a rare cause of acute tetra- or para-paresis in
      patients, who have had contact with schistosomes. Early diagnosis is essential
      because of the excellent prognosis with specific therapy.

PMID- 11311477
TI  - Respiratory failure caused by Chiari I malformation with associated
      syringomyelia.
AB  - The authors report a case of a 38-year-old male with a Chiari I malformation and
      syringomyelia that presented with acute respiratory distress. Pulmonary function
      testing was consistent with respiratory muscle weakness. A suboccipital
      craniectomy and C1, 2, 3 laminectomies were performed on an emergent basis.
      Postoperatively the patient had significant improvement in his respiratory status
      associated with a reduction in the size of the syringomyelia on follow-up
      imaging.

PMID- 11311478
TI  - Adrenocortical carcinoma with cerebral metastasis in a child: case report and
      review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Adrenocortical carcinoma (ACC) is rare in the pediatric
      population, and brain metastasis seldom occurs. CLINICAL PRESENTATION: The
      authors report a case of metastatic ACC to the brain in a 9-year-old patient who
      had an adrenal cortex neoplasm removed at 4 years of age, and was free of
      symptoms for 5 years. Two weeks before admission she complained of blurred vision
      in both eyes. INTERVENTION: Examination revealed bilateral papilledema, and a
      Magnetic Resonance Imaging (MRI) of the brain revealed a mass in the left lateral
      ventricle with extensive vasogenic edema and hydrocephalus. The tumor was
      removed, and histopathologic examination demonstrated metastatic ACC. CONCLUSION:
      Although ACC is a rare neoplasm it must be considered in the differential
      diagnosis of cerebral lesions in patients with a history of this tumor. Periodic
      long-term brain imaging is suggested as part of the follow up in patients with
      adrenocortical neoplasms.

PMID- 11311479
TI  - Solid-calcified colloid cyst of the third ventricle.
AB  - We report a 65-year-old female with a solid-calcified colloid cyst in the third
      ventricle that was demonstrated on computed tomography scan and magnetic
      resonance images. The lesion was surgically excised using the anterior
      transcallosal-transforaminal approach. Complete preservation of the surrounding
      neural and vascular structures was achieved.

PMID- 11311480
TI  - Sensory perineuritis presented as a mononeuritis multiplex associated with livedo
      vasculitis.
AB  - We report a 52-year-old patient affected by a mononeuritis multiplex and livedo
      vasculitis. Sural nerve biopsy showed mild thickening of the perineurium,
      vascular alterations with inflammatory cell infiltration in the perineurium, and
      remarkable loss of large and small myelinated fibers. A therapeutic trial of
      acetylsalicylic acid, danazol, and dipyridamole controlled the skin lesion
      without improvement of nerve conduction studies.

PMID- 11311481
TI  - Multiple nocardial abscesses of cerebrum, cerebellum and spinal cord, causing
      quadriplegia.
AB  - In this paper we present a case of a diabetic patient with nocardial abscesses of
      cerebrum, cerebellum and the spinal cord. The present case is the first case in
      the literature of solitary intramedullary abscess in cervical spinal cord,
      causing tetraplegia. Nocardia asteroides grew in a culture of the abscess pus.
      After either surgical excision or drainage of lesions, a triple combination
      regimen of chemotherapy (amikacin, ceftriaxone and trimethoprim-sulfamethoxazole)
      was given, but the patient was lost in the postoperative period. This case gives
      suggestive evidence of an association between cervical spinal cord involvement
      and poor prognosis in CNS nocardiosis.

PMID- 11311483
TI  - Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder
      carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse
      transcription-polymerase chain reaction.
AB  - Significant sex differences exist among cases of bladder cancer in humans as well
      as in experimental animals such as rats. Aromatic amines such as benzidine and 2
      naphthylamine are known to induce bladder cancer. These carcinogenic amines are
      activated to genotoxic substances by cytochrome P 450 CYP4B1, which is present in
      bladder mucosa. In this study, regulation of CYP4B1 was investigated to elucidate
      sex difference in bladder carcinogenesis. Competitive reverse transcription
      polymerase chain reaction was used to investigate the expression of rat CYP4B1
      mRNA occurring in small amounts of tissue such as bladder tissue. Expression of
      CYP4B1 in the bladder of male rats increased with development but not in that of
      female rats. Moreover, mature male rats exhibited higher expression of CYP4B1 in
      the bladder than did mature female rats. Castration of male rats decreased CYP4B1
      levels and treatment with testosterone led to a partial recovery of CYP4B1
      levels. These results indicate that CYP4B1 levels in the rat bladder are partly
      regulated by androgens. Furthermore, the present findings suggest that the sex
      difference observed in bladder carcinogenesis was due to sex-different expression
      of CYP4B1 in bladder tissue.

PMID- 11311484
TI  - Chemopreventive effect of 2-(allylthio)pyrazine (2-AP) on rat colon
      carcinogenesis induced by azoxymethane (AOM).
AB  - An investigation was conducted to assess the chemopreventive effects of 2
      (allylthio)pyrazine (2-AP), synthesized for potential use as a chemopreventive
      agent, after administration during the pre-initiation and post-initiation stages
      in a rat colon carcinogenesis model with azoxymethane (AOM). One hundred, 5-week
      old, male F344 rats were randomly divided into two experiments (n = 50 each).
      Experiment 1 rats were randomly divided into three groups: Group 1 rats were pre
      treated with 2-AP (25 or 50 mg/kg body weight, 3 consecutive days through the
      route of intragastric intubations) before AOM (20 mg/kg body weight, single
      subcutaneous (s.c.) injection) initiation. Group 2 rats were treated with AOM
      alone. Group 3 rats were given 2-AP alone without AOM initiation. The animals
      were killed at the end of each experiment (week 5) and the aberrant crypt foci
      (ACF) of the colonic mucosa were assessed after staining with methylene blue.
      Experiment 2 rats were randomly divided into three groups: Group 1 rats were
      given 2-AP (10, 25 or 50 mg/kg body weight, five-times intragastric intubations
      per week for 5 weeks from week 3) after AOM (15 mg/kg body weight, three s.c.
      injections) initiation for 2 weeks. Group 2 rats were treated with AOM alone.
      Group 3 rats were given 2-AP alone without AOM initiation. The animals were
      killed at the end of the experiment (week 8) and the ACF of the colonic mucosa
      were quantified. Total numbers of ACF/colon in Group 1 rats (pre-treated with 2
      AP) tended to decrease (2-AP, 50 mg/kg body weight) or increase (2-AP, 100 mg/kg
      body weight) depending on the dose level. Total numbers of ACF/colon in Group 1
      rats (treated with AOM followed by 2-AP, all subgroups; 160.8 +/- 38.0; 161.8 +/-
      38.1; 137.1 +/- 48.4) were decreased significantly compared with the values in
      Group 2 rats (AOM alone; 214.8 +/- 48.1) (P < 0.05 or 0.01). The highest dose
      group (2-AP, 50 mg/kg body weight) had the lowest levels of total numbers of
      ACF/colon among the three subgroups. Total numbers of aberrant crypts (AC)/colon
      of the highest dose group (340.1+/- 117.9) decreased significantly compared with
      the value for Group 2 rats (AOM alone; 545.1 +/- 38.3). These results thus
      suggest that 2-AP may have potential as a chemopreventive agent against rat colon
      carcinogenesis after administration of AOM during the post-initiation stage.

PMID- 11311485
TI  - Allelotype analysis of gallbladder carcinoma associated with anomalous junction
      of pancreaticobiliary duct.
AB  - Anomalous junction of pancreaticobiliary duct (AJPBD) patients has an increased
      risk of gallbladder and bile duct carcinomas. However, the relevance of carcinoma
      with AJPBD is not fully clarified. We performed analysis of loss of
      heterozygosity (LOH) at p53 locus and immunohistochemistry of p53 and K-ras gene
      mutation in five cases of gallbladder carcinoma associated with AJPBD. LOH of p53
      locus and overexpression of p53 were detected in two out of five (40%) and five
      out of five (100%), respectively, in the present study. K-ras gene mutation at
      codon 12 and 13 was not detected (0%, 0/5). These results suggest that
      aberrations of p53 are involved in carcinogenesis of gallbladder carcinoma
      associated with AJPBD. Next, in order to find the genetic events besides K-ras
      mutation and overexpression of mutant p53 in this disease, LOH analysis was
      performed using 72 microsatellite markers. High frequency of allelic loss (> 50%)
      was found on 2p (81.8%), 4p (50%), 4q (50%), 8q (60%), 9q (50%), 10p (50%), 14p
      (60%), 14q (50%), 16p (60%), 19p (50%), 21p (50%) and Xp (66.6%). The highest
      deletion regions on chromosome 2p24 (3/3, 100%), 14q22 (3/4, 75%) and 21q22 (3/4,
      75%) were found. The present study suggests that gallbladder carcinoma associated
      with AJPBD has high frequent allelic loss and has two new regions which may
      harbor putative tumor suppressor genes.

PMID- 11311486
TI  - Inhibitory effects of 6-O-acylated L-ascorbic acids possessing a straight- or
      branched-acyl chain on Epstein-Barr virus activation.
AB  - 6-O-Acylated L-ascorbic acids possessing a straight- or branched-acyl chain of
      varying length from C(4) to C(18) have been synthesized and evaluated their anti
      tumor promoting effects on the activation of the Epstein-Barr virus early
      antigen. The derivatives having a straight- or branched-acyl chain of C(6) to
      C(11) carbon atoms exhibited marked effects.

PMID- 11311487
TI  - Preventive effect of germanium dioxide on the inhibition of gap junctional
      intercellular communication by TPA.
AB  - Gap junctional intercellular communication (GJIC) is thought to be essential for
      maintaining cellular homeostasis and growth control. In order to detect any
      protective agent against tumor formation, we examined the anticarcinogenic effect
      of a germanium dioxide (GeO(2)) using a model system of GJIC in F344 rat liver
      epithelial cells, named WB cells. 12-O-tetradecanoylphorbol-13-acetate (TPA),
      known as tumor promoters, inhibited GJIC in the epithelial cells as determined by
      the scrape loading/dye transfer (SL/DT) assay. And GeO(2) recovered this
      inhibition of GJIC. Immunostaining of connexin 43 (Cx43) protein in WB cells
      indicated that TPA caused a loss of Cx43 protein from the cell membranes.
      However, GeO(2) treatment showed re-appearance of Cx43 protein on the membrane.
      Reverse transcription-polymerase chain reaction (RT-PCR) and Western blots were
      analyzed to determine whether the test compounds might have altered the steady
      state levels of gap junction mRNA and/or connexin protein levels or
      phosphorylation. The inhibition of GJIC by TPA in WB cells was correlated with
      the hyperphosphorylation of Cx43 as measured by mobility shifts of the western
      blot bands of Cx43. TPA induced hyperphosphorylation of Cx43 protein, while
      GeO(2) appeared to partially block this hyperphosphorylation. Here, we showed
      that pre- and co-incubation with GeO(2) in TPA-treated WB-cells abolished down
      regulation of GJIC by TPA. These data suggest that GeO(2) may inhibit tumor
      promotion by enhancing GJIC.

PMID- 11311488
TI  - Cryopreserving whole blood for functional assays using viable lymphocytes in
      molecular epidemiology studies.
AB  - There is an increasing need for viable lymphocytes in performing phenotypic
      assays for biomarker studies. Both fresh and cryopreserved lymphocytes have been
      used for cell culture-based functional assays. However, fresh lymphocytes do not
      allow assays to be done in batches and cryopreservation of isolated lymphocytes
      results in a considerable loss of viable cells. To investigate the feasibility of
      using cryopreserved whole blood as a source of viable lymphocytes in molecular
      epidemiology studies, two well-established biomarkers, the host-cell reactivation
      (HCR) and mutagen sensitivity assays, were used to compare the method of
      cryopreserving whole blood with the traditional methods. In 25 paired blood
      samples assayed for DNA repair capacity (DRC) by the HCR assay, the DRC values of
      frozen whole blood (mean +/- SD, 11.59 +/- 3.07) were similar to those of frozen
      isolated lymphocytes (11.08 +/- 3.50). The correlation between the paired DRC
      values was 0.77 (P < 0.001). In 31 paired blood samples assayed for the gamma
      radiation-induced chromatid breaks by the mutagen sensitivity assay, there was no
      significant difference between the baseline level of chromatid breaks in
      lymphocytes from frozen blood (0.05 +/- 0.03) and fresh blood (0.06 +/- 0.03).
      The blastogenic rate and mitotic index of the cells used for the two assays were
      compared between the different processing methods. The lymphocytes from frozen
      whole blood were more sensitive to gamma-radiation, with a higher mean level of
      chromatid breaks (0.68 +/- 0.21) than that in fresh blood (0.42 +/- 0.12, P <
      0.01), and the correlation between the numbers of chromatid breaks in the paired
      samples was statistically significant (r = 0.61, P < 0.001). These data suggest
      that within the limits of the parameters investigated here, cryopreserved whole
      blood is a good source of viable lymphocytes for biomarker assays in molecular
      epidemiological studies.

PMID- 11311489
TI  - Methylation changes in promoter and enhancer regions of the WT1 gene in Wilms'
      tumours.
AB  - Although the WT1 gene has been implicated in the aetiology of Wilms' tumour,
      mutations in WT1 are found only in minority of the tumours. DNA methylation of
      regulatory elements represents another possibility of modulation of gene
      expression. We studied methylation in the promoter and enhancer regions of the
      WT1 gene in 34 Wilms' tumour patients by the polymerase chain reaction on HpaII
      digested DNA and by the bisulphite method. No methylation was detected in the
      promoter region in either tumour or normal kidney or blood DNA samples. In
      contrast, a HpaII site in the enhancer region was at least partially methylated
      in normal kidney and blood DNA samples and in about one-third of the tumours,
      while the majority of tumours showed no methylation. The differential methylation
      in the enhancer region of the WT1 gene may indicate that methylation of this
      element can play a role in the regulation of this gene.

PMID- 11311490
TI  - Fetal fetuin selectively induces apoptosis in cancer cell lines and shows anti
      cancer activity in tumor animal models.
AB  - An apoptosis-inducing protein with molecular weight of 60 kDa has been purified
      from fetal bovine serum. The N-terminal amino acid sequence of this protein (e.g.
      I-P-L-D-P-V-A-G-Y-K) reveals that it is bovine fetuin, a fetal protein
      functioning to control embryogenesis. The apoptosis-inducing activity of fetuin
      is totally dependent on zinc. Depletion of zinc ion from fetuin or substitution
      of zinc ion by barium ion completely abolished the apoptosis-inducing activity of
      fetuin. Interestingly, while the fetuin isolated from fetal serum selectively
      induces apoptosis in cancer without affecting normal cells, the fetuin isolated
      from mature serum is completely inactive. This suggests that the biological
      activity of fetuin is under developmental regulation. In vivo, tumor animal model
      studies showed that fetuin enhanced survival by up to 141% in P388 leukemia
      animal model in mice. Fetuin was also found to inhibit prostate cancer formation
      in a PC-3 prostate cancer model in mice.

PMID- 11311491
TI  - Expression of Wnt genes in human colon cancers.
AB  - A polymerase chain reaction-based approach was used to study the expression of
      Wnt genes in human colon carcinoma tissue and normal colon mucosa. In a number of
      cases Wnts 2, 4, 5a, 6 and/or 7a were found to be more highly expressed in colon
      carcinoma tissue compared to surrounding normal-appearing mucosa from the same
      patients. Wnts 4, 5a, 6 and 7a, but not 2, were also found to be expressed in
      colon cancer cell lines. The increased levels of expression of these Wnt genes in
      tumor tissue may indicate their possible involvement in human colon
      tumorigenesis.

PMID- 11311492
TI  - Association analysis of somatostatin receptor (SSTR1 and SSTR2) polymorphisms in
      breast cancer and solar keratosis.
AB  - The presence of somatostatin receptors (SSTR1-5) in tumour cells indicates a
      potential for somatostatin to bind and suppress growth, as well as allowing for
      therapeutic treatment with somatostatin analogues. The genes for SSTR1 and SSTR2
      have been shown to contain dinucleotide repeat polymorphisms. We have performed
      association studies on breast cancer and solar keratosis populations to determine
      whether these genes play a role in the development of these conditions. Results
      showed that there was no significant difference between SSTR1 and SSTR2
      polymorphism frequencies in the tested breast cancer population (P = 0.59 and P =
      0.54, respectively) nor the solar keratosis population (P = 0.10 and P = 0.883,
      respectively) as compared to unaffected populations. Hence, these studies do not
      support a role for these receptor genes in either breast cancer or solar
      keratosis lesions.

PMID- 11311493
TI  - Alteration of cyclin D1 and CDK4 gene in carcinoma of uterine cervix.
AB  - Amplification and overexpression of cyclin D1 and CDK4 genes in cervical
      carcinoma were studied by semi-quantitative differential polymerase chain
      reaction assay and an immunostaining technique, respectively. Amplifications of
      cyclin D1 and CDK4 genes were found in 24% (27/113) and 26% (29/112) of tumors,
      respectively. Overexpression of cyclin D1 and CDK4 was demonstrated in 32%
      (21/66) and 73% (45/62) of tumors, respectively. No tumor showed CDK4 gene
      mutation on single strand conformational polymorphism. Sixteen percent (8/49) of
      the tumor specimens showed neither amplification nor overexpression. Disease
      stage, tumor grade and overexpression of cyclin D1 were found to be independent
      poor prognostic factors in cervical carcinoma.

PMID- 11311494
TI  - Follicle-stimulating hormone promotes the growth of human epithelial ovarian
      cancer cells through the protein kinase C-mediated system.
AB  - We have previously described that follicle-stimulating hormone (FSH) stimulated
      the growth of human epithelial ovarian cancer tissues and cells. In order to
      determine the signaling pathway on FSH action in ovarian cancer, we used an
      epithelial ovarian cancer cell line (HRA line) which constitutively FSH receptors
      (FSHRs). FSH significantly increased cell proliferation (230.1 +/- 20.5%, P <
      0.05) and (3)H-thymidine uptake (443.5 +/- 35.1%, P < 0.01). 1-(5
      Isoquinolinesulfonyl)-2-methyipiperazine (H7, 1 5 nM), staurosponine (STR, 5 nM)
      and calphostin C (5 nM), specific protein kinase C (PKC) inhibitors,
      significantly suppressed the FSH-stimulated cell growth (120.2-140.2%, P < 0.05)
      and (3)H-thymidine uptake (140.5-173.9%, P < 0.05), whereas N-(2-guanidinoethyl)
      5-isoquinoline-sulfon-amide (HA1004, l5 nM), which is a derivant of H7 and
      inhibits most of protein kinases except PKC, showed no effect on the FSH
      stimulated cell growth and (3)H-thymidine uptake. A pretreatment with 12-0
      tetradecanoylphorbol-13 acetate (TPA, 100 ng/ml) or STR (20 nM) significantly
      suppressed the subsequent FSH-stimulated cell growth (TPA; 152.3 +/-10.3%, STR;
      160.4 +/- 15.9%, P < 0.05) and (3)H-thymidine uptake (TPA; 250.4 +/-18.3%, STR;
      208.7 +/- 15.9%, P < 0.05). STR abolished the suppression of TPA preincubation on
      the subsequent FSH-stimulated cell growth and (3)H-thymidine uptake. HRA cells
      constitutively expressed PKCalpha but not PKCbeta nor PKCgamma. The levels of
      either expression of PKCalpha protein and mRNA were significantly amplified by
      FSH. These data suggest that stimulation of PKCalpha transcription is involved in
      the FSH-stimulated cell growth and DNA synthesis in epithelial ovarian cancer
      cells.

PMID- 11311495
TI  - Cell differentiation and chemotherapy influence p53 and Mdm2 immunoreactivity in
      human HT29 colon cancer cells grown in scid mice.
AB  - Absence of a functional p53 gene product can lead to increased p53 accumulation
      in cancer cells. In this contribution, the association between cell
      differentiation, chemotherapy and p53 immunoreactivity in human HT29 colon cancer
      cells grown in scid mice as undifferentiated cells and as mucin containing signet
      ring cells was investigated. Mutated p53 was more frequently expressed in the
      undifferentiated tumour cells than in the signet-ring cells. 5-fluorouracil (5FU)
      treatment resulted in a substantial increase in the p53-positive signet-ring cell
      population (from 17% to 45%) and in an increased Mdm2 immunoreactivity. These
      findings indicate that mutated p53 expression is related to the differentiation
      pattern and that tumour cells devoid of mutated p53 immunoreactivity are
      preferentially eliminated by 5FU treatment.

PMID- 11311496
TI  - The mode of cell death in H-358 lung cancer cells cultured with inhibitors of 5
      lipoxygenase or the free radical spin trap, NTBN.
AB  - The 5-lipoxygenase inhibitors SC41661A and MK886 with different mechanisms of
      action and the free radical spin trap, NTBN inhibit proliferation of the human
      bronchiolar lung cancer cell line NCI H-358 (5807 CRL). With continued culture,
      the agents induced a form of programmed cell death in which DNA laddering was not
      detected and ultrastructural changes were not characteristic of classic 'type 1'
      cellular suicide. The changes were more consistent with a type 2 cytosolic,
      autophagic form of PCD. MK886 induced strikingly abnormal mitochondrial
      morphology. Since the lipoxygenase inhibitors and NTBN induce classic type 1 PCD
      in U937 monoblastoid cells, these agents can activate either pathway, depending
      upon cell type. It is not certain whether activation of type 1 or 2 pathways
      depends entirely upon cell lineage and/or initiating agent, if all cells retain
      both pathways, and if type 1 PCD a more effective mediator of the process. These
      are all relevant questions for assessing the impact of PCD on malignant cell
      survival and considering ways in which it might be enhanced.

PMID- 11311497
TI  - Expression of apoptosis related proteins in brains of patients with Alzheimer's
      disease.
AB  - An increasing number of proteins are implicated in apoptosis and several of them
      have been shown to be altered in Alzheimer's disease (AD) brain. Because of this
      apoptosis is thought to be the underlying mechanism of neuronal cell loss in AD.
      To further substantiate this hypothesis we investigated the expression of a
      recently identified apoptosis related proteins and other apoptosis regulators in
      frontal cortex and cerebellum of AD by Western blot and enzyme-linked
      immunsorbent assay technique. Quantitative analysis revealed unaltered levels of
      Bax and RAIDD (Receptor interacting protein associated ICH-1 (caspase-2)/CED-3
      (Caenorhabditis elegans death protease-3)-homologous protein with death domain)
      in both regions. ZIP (Zipper interacting protein) kinase, Bim/BOD (Bcl-2
      interacting mediator of cell death/Bcl-2 related ovarian death gene) and p21 were
      significantly increased only in AD frontal cortex (P < 0.05, in all cases).
      Cerebellar Bcl-2 levels were significantly increased in AD (P < 0.01) while in AD
      frontal cortex, although the levels tended to increase did not reach significance
      level. The results indicate that apoptosis indeed account for the neuronal loss
      in AD. However, it does not seem to involve Bax and RAIDD.

PMID- 11311498
TI  - The effect of expertise in gymnastics on postural control.
AB  - The goal of this paper was (1) to investigate if gymnasts have a more stable
      standing posture than experts in other sports, and (2) to determine how much
      gymnasts are affected by the removal of vision in different postural tasks. Six
      expert gymnasts and six experts in other non-gymnastic sports were asked to
      maintain balance in three standing postures of increasing difficulty: bipedal,
      unipedal, and unipedal + unstable support (i.e. 7 cm thick foam surface). Each
      posture was tested successively with and without vision. Based on the
      displacement of the center of pressure (range and mean average speed), the
      results showed that when visual cues were available, postural sway increased with
      the difficulty of the task, but both groups had comparable performance in all the
      tasks. When vision was removed, although both groups demonstrated larger postural
      sway in the unipedal tasks, this effect was less accentuated for the gymnasts. We
      concluded that gymnasts are able to use the remaining sensory modalities to
      compensate for the lack of vision in unstable postures.

PMID- 11311499
TI  - The Apolipoprotein E genotype in patients affected by syndromes with focal
      cortical atrophy.
AB  - The role of the Apolipoprotein E (APOE) alleles in syndromes associated with
      focal cerebral atrophy (fronto-temporal dementia, primary progressive aphasia,
      corticobasal degeneration) is still controversial. We studied the APOE allele
      distribution in 39 patients with clinically diagnosed syndromes associated with
      focal cerebral atrophy (FCA), in 50 patients with early-onset probable
      Alzheimer's disease (EOAD), and in 60 patients with late-onset probable AD
      (LOAD). The APOE genotype was determined from a blood sample, using polymerase
      chain reaction and restriction enzyme digestion. The APOE epsilon4 allele
      frequency was significantly higher in the EOAD (21.0%) and LOAD (33.3%) groups,
      but not in the FCA group (5.1%), as compared with controls. In our population,
      the epsilon2 allele frequency was significantly higher in patients with FCA
      (12.8%) than in controls (4.8%). These results show that the APOE epsilon4 allele
      is not a risk factor for syndromes associated with FCA. The potential role of the
      epsilon2 allele in these syndromes needs further investigation.

PMID- 11311500
TI  - The Cycloxygenase-2 inhibitor SC58236 is neuroprotective in an in vivo model of
      focal ischemia in the rat.
AB  - Focal ischemia was induced in the fronto-parietal region of rat brain, by
      injection of Rose Bengal, followed by light activation. Focal ischemia was
      accompanied by formation of PGD(2) peaking 60-90 min post irradiation and
      declining thereafter. Increased Cycloxygenase-2 (COX-2) expression was also
      observed. Control ischemic rats showed distinct morphological alterations with
      necrosis of neurons, glial cells and blood vessels, surrounded by a halo with
      pyknotic cells with cytoplasm swelling and vacuolization. Compound SC58236, a
      selective COX-2 inhibitor, dose-dependently prevented, ischemia-induced
      eicosanoid formation (area under the curve (AUC) of controls: 3.11 +/- 0.87; AUC
      of 20 mg/kg SC58236: 0.39 +/- 0.24), and caused significant reduction of damaged
      area (30.7 and 18.9% at SC58236 20 and 6.6 mg/kg), suggesting that selective
      inhibitors of COX-2 are neuroprotective.

PMID- 11311501
TI  - Effect of the glycine modulatory site of the N-methyl-D-aspartate receptor on
      synaptic responses in kitten visual cortex.
AB  - In visual cortical slices taken from kittens, the administration of D-serine, an
      agonist of the N-methyl-D-aspartate receptor complex, significantly enhanced
      synaptically evoked responses using field potential recordings in lower layer
      II/III. Expression of normally appearing long-term potentiation (LTP) took place
      in the presence of the agonist during high-frequency stimulation (HFS). The
      administration of an antagonist of this receptor, 7-chloro-kynurenic acid (7-Cl
      KY) alone had no appreciable effect on low-frequency synaptic transmission while
      HFS failed to induce LTP. Combined administration of D-serine and 7-Cl KY
      resulted in no alteration of low-frequency synaptic transmission, although
      expression of LTP was normally obtained. These results suggest that in visual
      cortex of kittens, the availability of this glycine binding site of the NMDA
      receptor is necessary for the expression of LTP.

PMID- 11311502
TI  - Nomifensine-induced c-fos mRNA expression in discrete brain areas of the
      developing rat.
AB  - In rats, the subcutaneous injection of a dopamine uptake inhibitor, nomifensine
      (40 mg/kg), induced a significant increase in the c-fos mRNA levels in the
      neocortex on postnatal days 23 and 49, in the striatum on days 8, 14, 23 and 49,
      and in the hippocampus on day 23, when compared with saline administration. The
      repeated injection with nomifensine (40 mg/kg once daily) from postnatal days 49
      to 53 and from 23 to 27, but not from days 8 to 12 and 14 to 18, resulted in an
      enhanced stereotypy response elicited by a subsequent challenge of the drug (5
      mg/kg) 21 days after the last injection (behavioral sensitization). The present
      results suggest that the neuronal circuits regulated by nomifensine might undergo
      regionally-different developmental changes, which could be implicated in the
      development of behavioral expressions including nomifensine-induced stereotypy
      sensitization.

PMID- 11311503
TI  - Localization of molluscan cardioexcitatory tetrapeptide in the brain of African
      Cichlid fish (Haplochromis burtoni) revealed by immunocytochemistry.
AB  - The FMRFamide-like immunoreactivity was investigated in the brain of African
      cichlid fish, Haplochromis burtoni, in which sexual maturation is under social
      control. In both dominant and subdominant males and females, the FMRFamide
      immunoreactive (ir) cells were found only in the nucleus olfacto-retinalis and in
      the nucleus of the midbrain tegmentum. However, several FMRFamide-ir fibers were
      seen in the olfactory bulb and throughout the entire brain of both male morphs
      and female fish. As the role of nucleus olfacto-retinalis is well known in
      chemoreception, these results suggest the involvement of FMFRamide-like peptide
      in the chemosensory control of reproductive behavior in this species.

PMID- 11311504
TI  - Modulation of soleus H-reflex following ipsilateral mechanical loading of the
      sole of the foot in normal and complete spinal cord injured humans.
AB  - The modulation of the soleus H-reflex in response to tonic mechanical loading
      applied to the plantar aspect of the foot sole was examined in nine normal
      subjects and five patients with a clinically defined complete spinal cord injury
      (SCI). With the subjects seated, tonic pressure applied to the metatarsal region
      of the ipsilateral foot sole significantly depressed soleus H-reflex excitability
      in all subjects. The demonstration of a decrease in H-reflex excitability in both
      subject groups as a result of applied pressure to the foot suggests that the
      change in reflex excitability is the result of a common spinal mechanism. The
      results highlight the modulatory effects that natural stimulation of cutaneous
      afferents can have on reflex excitability and may have practical application in
      gait rehabilitation and in the management of disorders of muscle tone following
      SCI.

PMID- 11311505
TI  - Genetic variation in the 5-HT5A receptor gene in patients with bipolar disorder
      and major depression.
AB  - In the present study, genetic variation of the 5-HT5A receptor was analyzed in
      patients affected by affective disorders and healthy controls. The sample
      consisted of 181 patients with major depression, 88 patients with bipolar
      affective disorder (BP) and 157 unrelated controls (C), all of Spanish origin.
      Two polymorphisms (-19G/C and 12A/T) in the 5-HT5A receptor gene were analyzed by
      polymerase chain reaction amplification and subsequent enzyme digestion. No
      genotype, allele or haplotype differences were found when we compared patients
      and controls. When clinical variables were considered as possible tools for
      detecting genetic heterogeneity, no differences were found. Our results suggest
      that the polymorphisms analyzed in the 5-HT5A receptor gene do not play a major
      role in the pathogenesis of affective disorders.

PMID- 11311506
TI  - Affective picture processing: event-related synchronization within individually
      defined human theta band is modulated by valence dimension.
AB  - Event-related desynchronization (ERD) and synchronization (ERS) in the theta
      frequency band was measured while subjects viewed stimuli with differing
      emotional content (from the International Affective Picture System). A
      significant valence by hemisphere interaction emerged only in the anterior
      temporal regions, showing relatively greater right hemisphere ERS for negative
      and left hemisphere ERS for positive stimuli. In turn, in the posterior brain
      regions affectively valenced vs neutral stimuli prompted larger extent of ERS
      against the background of the overall right hemisphere dominance in theta
      synchronization. The findings document that valence discrimination is associated
      with the early (200-500 ms poststimulus) time-locked synchronized theta activity
      as well as hemispheric asymmetries in anterior-posterior direction.

PMID- 11311507
TI  - Serotonin-2A-receptor and -transporter polymorphisms: lack of association in
      patients with major depression.
AB  - Disturbances in serotonergic neurotransmission system have been implicated in the
      etiology of mood disorders. As the importance of genetic factors is well
      established, genes encoding for proteins of the serotonergic pathway are
      important candidates to unravel the underlying genetic contribution. We examined
      two polymorphisms in the serotonin-2A-receptor gene (5-HT2A; T102C and His452Tyr)
      and the insertion/deletion polymorphism in the promoter region of the serotonin
      transporter (5-HTTLPR) in a sample of 173 patients with major depression and 121
      healthy controls. No statistical significant differences between patients and
      controls were found for any of the three investigated polymorphisms, neither in
      the distribution of the genotypes nor in allele frequencies. However, concerning
      the 5-HTTLPR polymorphism, the frequency of S/S (short allele) homozygotes was
      higher (23.1%) than in the control group (14.0%), but this failed to reach
      significance. Moreover we observed a different treatment response in patients
      with one or two C-alleles of the T102C polymorphism, with a significantly higher
      decrease in HAMD-17 (ANOVA: d.f. = 1, F = 5,288, P = 0.023) after 4 weeks of
      antidepressant treatment. Overall our results suggest that the investigated 5
      HT2A and 5-HTTLPR polymorphisms are not major susceptibility factors in the
      etiology of major depression. However, subtypes might be identified at least on a
      basis of differential treatment response.

PMID- 11311508
TI  - Post-training injections of catecholaminergic drugs do not modulate fear
      conditioning in rats and mice.
AB  - Studies employing classical fear conditioning (FC) and inhibitory avoidance (IA),
      two procedurally different aversive tasks, provide different insight into the
      neuronal mechanism(s) underlying fear learning. We examined whether immediate
      post-training injections of catecholaminergic drugs modulate memory consolidation
      in one-trial FC, as has been demonstrated in one-trial IA. Neither epinephrine
      (0.1, 0.3, 1.0 mg/kg intraperitoneally) nor amphetamine (1.0, 2.0 mg/kg)
      modulates FC to tone or context, as indicated by freezing in rats. Similarly,
      epinephrine (0.1, 1.0 mg/kg) and beta-adrenergic antagonists (sotalol and
      propranolol; 2 mg/kg) also failed to modulate FC in mice. These results indicate
      that FC is not susceptible to memory modulation by catecholaminergic drugs in the
      manner described in IA tasks.

PMID- 11311509
TI  - Interplay of biomechanical and neuromuscular constraints on pattern stability and
      attentional demands in a bimanual coordination task in human subjects.
AB  - Recent debate has focused upon the issue of whether general principles and laws
      of movement coordination may be derived without reference to anatomical,
      mechanical and physiological mechanisms. It has been proposed that self-generated
      movement involves the interaction of biomechanical and neuromuscular constraints.
      Biomechanical constraints are usually considered of as arising from the pendular
      dimensions of the limb or limb segments whereas neuromuscular constraints are
      commonly associated with nervous and metabolic control processes. The present
      study aims to investigate the interplay between these two different constraints
      on bimanual pattern stability and attentional demands. Five subjects were asked
      to execute an anti-phase coordination pattern (180 degrees of relative phase),
      while gradually increasing the frequency of oscillation and changing the
      rotational inertia of the joysticks. Frequency manipulation was expected to
      affect the neuromuscular constraints. Inertial manipulation was expected to
      affect biomechanical constraints. Attentional demands, reflecting the central
      cost associated with the maintenance of the coordination pattern was assessed
      using a dual-task paradigm. The results showed that: (1) increasing the
      oscillation frequency altered both coordination dynamics and attentional demands
      associated with the maintenance of bimanual coordination patterns; (2)
      manipulation of rotational inertia of the joysticks also altered pattern
      stability (standard deviation of relative phase) and coordination dynamics (i.e.
      the number of phase transition and the before transition), but these alterations
      were not paralleled by a change in attentional demands.

PMID- 11311510
TI  - Synergistic stimulation, by tumor necrosis factor-alpha and interferon-gamma, of
      fractalkine expression in human astrocytes.
AB  - Fractalkine is a CX3C chemonkine that appears to be a neuron-to-microglia signal
      molecule in the central nervous system. We studied the expression of fractalkine
      in normal human astrocytes in culture, by using semi-quantitative reverse
      transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. We
      found that tumor-necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) synergistically enhance the expression of fractalkine. The expression of
      both fractalkine mRNA and protein was increased in time- and concentration
      dependent manners in the cells co-stimulated with TNF-alpha and IFN-gamma.
      Cycloheximide, an inhibitor of protein synthesis, and dexamethasone had no effect
      on the synergy of the stimulation of fractalkine expression. We conclude that
      normal human astrocytes produce fractalkine by co-stimulation with pro
      inflammatory cytokines and it may serve as a potential signal for immune and
      inflammatory responses in the central nervous system.

PMID- 11311511
TI  - Facilitatory effect of substance P on learning and memory in the inhibitory
      avoidance test for goldfish.
AB  - The aim of this study was to investigate if substance P (SP) can improve learning
      and memory processes in goldfish, using an inhibitory avoidance test. A two
      compartment aquarium with a central sliding door was used. The animals were
      placed in the white compartment, and after 20 s the door was opened. As they
      entered the dark compartment, a weight was dropped in front of them. This
      procedure was repeated three times. After training, the animals were injected
      intraperitoneally with SP or vehicle. Twenty-four hours after training, the
      animals were tested and their latency was recorded. The group injected with SP
      showed an increase in the latency on the test day as compared with the vehicle
      group. These results suggest SP can facilitate memory in goldfish in an
      inhibitory avoidance test.

PMID- 11311512
TI  - Silicones in the rehabilitation of burns: a review and overview.
AB  - This article gives an overview of the use of silicones in the treatment and
      prevention of hypertrophic (burn related) scars. Of all non-invasive treatment
      modalities the use of continuous pressure and occlusive contact media, e.g.
      silicones, seem to be generally accepted as the only ones that are able to manage
      hypertrophic scarring without significant side-effects. A summary of the current
      opinions of the assumed working mechanisms of pressure as well as silicones is
      given. The use of silicones, either alone or in combination with pressure, is
      discussed. The recent development of custom made silicone devices has led to
      combinations of both modalities. Some of these, including the inflatable silicone
      insert systems (ISIS), are shown and discussed.

PMID- 11311513
TI  - Effects of mechanical compression on hypertrophic scars: prostaglandin E2
      release.
AB  - An alteration in the normal process of tissue repair can lead to the formation of
      hypertrophic scars. The best prevention and control of hypertrophy, especially in
      burn scars, is achieved using elastocompression, through a mechanism not yet
      clarified. Various studies have shown that mechanical compression induces the
      release of prostaglandin E2 (PGE2) and that PGE2 increases the expression of
      collagenases. In this study, we evaluated the effect of mechanical compression in
      vitro on PGE2 release in human normotrophic (NS) and hypertrophic (HS) burn
      scars. PGE2 basal levels in HS were significantly lower than those present in NS,
      and compression induced a significant increase in the release of PGE2 in HS scar
      in remission (7.2 times basal level) and active stages (5.88 times basal level).
      This increase seemed to be only partially IL-1beta-dependent. These data suggest
      a role for PGE2 in the process of hypertrophy remission induced by pressure
      therapy.

PMID- 11311514
TI  - Epidemiology and mortality of burns in the South West of Iran.
AB  - Burn injuries still produce a significant morbidity and mortality in Iran. This
      study was carried out to analyze the epidemiology, mortality, and current
      etiological factors of 2043 burn patients who were admitted to the burn centers
      in the Fars province during 4 years (1994-1998). There were two burn centers in
      the Fars province serving 3817036 people over an area of 124,000 km(2). The
      overall incidence rates of hospitalization and death were 13.4 and 4.6 per 100000
      person-years. The mean age was 21.9 years, and 51% of patients were children
      under 19-years-old. The highest rates of hospitalization and death were observed
      in the elderly (80 years). Also young females (20-29 years) had a high rate of
      hospitalization. Thus, 55% of the patients had BBS less than 40%. Burn injuries
      were more frequent and larger with higher mortality in females than in males
      (P<0.0001). There was also statistically significant correlation between age
      groups, gender, and BBS with mortality rate (P<0.0001). Flame was the most common
      etiology of burns. There was also significant correlation between age groups and
      type of burns (P<0.0001). Suicide attempts for all the patients > or = 11 years
      were the cause of 41.3% (256/620) of the burns involving women and of 10.3%
      (40/388) of the burns involving men. The overall case fatality rate was 34.4%.
      The mortality rate was significantly higher for self-inflicted burns (78%) than
      for accidental burns (26.7%). Most of the lesions requiring hospital admission
      occurred during the winter months. Factors associated with an increase in
      mortality were suicidal burns, burn size, age, and flame burns. Most of the burn
      injuries were caused by domestic accidents and were, therefore, preventable.

PMID- 11311515
TI  - A review of suicides by burning in Rome between 1947-1997 examined by the
      Pathology Department of the Institute of Forensic Medicine, University of Rome
      'La Sapienza'.
AB  - The 34 cases of suicide by self-immolation admitted to the Institute of Forensic
      Medicine, University of Rome 'La Sapienza', during a 50-year period (1947-1997)
      were investigated. The nature of this phenomenon in relation to sex, age of the
      victims, location of the suicides and combination of methods used is discussed.
      Finally the distribution and extent and characteristics of the lesions are
      considered from a forensic point of view.

PMID- 11311516
TI  - An audit of the use of laser Doppler imaging (LDI) in the assessment of burns of
      intermediate depth.
AB  - This is the first report of an evaluation of the use of a laser Doppler imager
      (LDI) scanner in the assessment of burn depth in patients. It is based on a 6
      month, prospective audit of 76 burns of intermediate depth. Clinical and LDI
      assessments of burn wound depth were recorded at 48-72 h post-injury.
      Histological confirmation of depth was obtained from those burns requiring
      surgery. A healing time of less than 21 days was taken as confirmation of the
      injury being an superficial dermal burn. The accuracy of LDI in the assessment of
      burn depth was 97%, compared with 60-80% for established clinical methods. This
      audit confirms that LDI is a very accurate measurement tool for the assessment of
      burn wound depth. We recommend that all burns of intermediate depth should be
      analysed in this way in order to ensure appropriate management of the burn, to
      avoid unnecessary surgery and to reduce hospital stay and costs.

PMID- 11311517
TI  - Near infrared spectroscopic assessment of hemodynamic changes in the early post
      burn period.
AB  - Near infrared reflectance spectroscopy and imaging was used to assess non
      invasively the hemodynamic changes that occur in the early post-burn period in
      cutaneous burn injuries of varying depth. An acute porcine model was used to
      demonstrate the potential of near infrared spectroscopy and imaging to accurately
      determine the change in tissue oxygenation, blood volume and tissue water content
      following a thermal injury. Near infrared spectroscopy was used to monitor tissue
      at discrete locations, while spectroscopic imaging was able to survey large areas
      of tissue. Both methods were rapid and non-invasive. Tissue hemoglobin oxygen
      saturation, total hemoglobin and tissue water content were all affected by
      thermal injury and changed significantly over a 3 h post-burn monitoring period.
      Burns that ranged in severity between superficial and full thickness displayed a
      significantly different hemodynamic response. When the early post-burn profiles
      (1-3 h) of tissue hemoglobin oxygen saturation, total hemoglobin and tissue water
      content were considered jointly, injuries leading to superficial, intermediate
      partial thickness, deep partial thickness and full thickness burns could all be
      differentiated at high statistical significance. These results suggest that non
      invasive hemodynamic monitoring in the early post-burn period using near infrared
      spectroscopy may be of value in the early assessment of burn injury.

PMID- 11311518
TI  - Cardiac apoptosis in burned rats with delayed fluid resuscitation.
AB  - Clinical and experimental studies have shown that delayed fluid resuscitation
      postburn decreases heart function. We hypothesized that apoptosis occurs in the
      cardiomyocyte in this condition. To investigate this hypothesis, rats were
      burned, fluid resuscitation was delayed, and the integrity of cardiac genomic DNA
      in the burned rats was determined with an LM-PCR Ladder Assay kit. DNA
      fragmentation shown as DNA ladders on gels, the hallmark of apoptosis, was found
      in the heart tissue of these rats. In the early phase of delayed fluid
      resuscitation, the nuclear factor kappa B (NF-kappa B) was examined using an
      electrophoretic mobility shift assay and was found to be activated. In comparison
      with burned rats with immediate fluid resuscitation, nitric oxide levels in
      hearts from burned rats with delayed fluid resuscitation were significantly lower
      (P<0.01). These results suggest that apoptosis may be an important pathway for
      cardiac injury, which may result from the activation of NF-kappa B and decreased
      nitric oxide levels.

PMID- 11311519
TI  - Porcine small intestinal submucosa (SIS): a bioscaffold supporting in vitro
      primary human epidermal cell differentiation and synthesis of basement membrane
      proteins.
AB  - The growth pattern of human epidermal cells, fibroblasts or Swiss mouse 3T3/J2
      fibroblasts cultured upon the extracellular matrix (ECM) derived from small
      intestinal submucosa (SIS) was evaluated. The cell/SIS composites were grown
      submerged, then maintained in air/liquid interface for 2, 7, 10 or 14 days. The
      presence of differentiation-related keratins 10, 14 and 16, FN, laminin, collagen
      type VII and collagen type IV was determined by immunohistochemical methods in
      SIS alone and in the SIS/cell composite. Only FN could be detected in SIS alone.
      SIS supported the formation of an epithelial structure with suprabasal expression
      of K16 and regional suprabasal expression of K10. The epidermal cells were K14
      positive and tended to 'invade' the SIS to various degrees. Following the growth
      of epidermal cells and fibroblasts on the SIS substratum, immunolabeling of FN,
      laminin, collagen type VII and collagen type IV was observed in a cell-associated
      pattern. The fibroblasts commonly invaded the SIS, when co-cultivated with
      epidermal cells on the opposite side of the SIS. The ability of SIS to support
      epidermal cell/fibroblast attachment, migration and/or proliferation and
      differentiation with deposition of basement membrane (BM) components indicates
      that the composite model may be useful for studying cell-matrix interactions and
      for investigation as a dermal substitute.

PMID- 11311520
TI  - Cadaveric allograft discards as a result of positive skin cultures.
AB  - INTRODUCTION: The availability of cadaveric allograft is often limited by
      potentially pathogenic microbial organisms. Little data exists on cadaveric
      allograft discard rates related to positive microbiology. The purpose of this
      retrospective review was to determine the cadaveric allograft discard rates
      related positive microbiology and the subsequent breakdown of those organisms
      involved. METHODS: From January 1995 to June 1997, 1112 donors were screened and
      procured after informed consent had been obtained. The procedures used were in
      accordance with American Association of Tissue Banks (AATB) standards and
      guidelines. The number of discards due to positive skin cultures was reviewed and
      analyzed for type of microbial organism. RESULTS: Fifty-four donors (4.9%) were
      discarded due to positive skin cultures. Methicillin resistant Staphylococcus
      epidermidis, (MRSE), was the most predominant organism (22.2%), followed by gram
      negative rods as a group (18.5%), with Aspergillus species being the least
      predominant isolate. CONCLUSION: Despite the strict adherence to AATB protocol,
      microbial contamination of cadaveric allograft skin does not reach zero. It is
      not surprising that S. epidermidis was the predominant isolate, since skin is one
      of its common habitats. Continued vigilance in microbial testing remains
      paramount to ensure the quality of the allograft.

PMID- 11311521
TI  - Trends in blood conservation in burn care.
AB  - Traditional burn surgery is very bloody, but wide use of blood conserving
      strategies is becoming common. Uniform application of blood conserving techniques
      of burn wound excision may substantially decrease blood utilization in burn
      patients. We chose to examine this trend in our unit. All fresh frozen plasma
      (FFP) and packed red blood cell (pRBC) use in children with burns of 10% or more
      of the body surface who were admitted during 2-3 year intervals, separated by a
      decade, was reviewed in detail. Three subgroups were separately analyzed:
      children with 10-24% (small), 25-49% (medium) and 50-100% (large) body surface
      area burns. Between these two intervals a major emphasis was made in techniques
      of blood conservation during surgery and fresh frozen plasma was replaced by 5%
      albumin as the routine resuscitative colloid. In Group 1, there were 189
      children, of whom 184 (97%) survived to discharge. In Group 2, there were 203
      children, of whom 199 (98%) survived to discharge (N.S.). All subgroups were well
      matched for age, weight and burn size. Discharge hemocrits exceeded 30% in all
      subgroups. Reductions in FFP use were 100, 95 and 97% in the small, medium and
      large burn size groups, respectively. Reductions in pRBC use were 89, 63, and 80%
      in the small, medium and large burn size groups, respectively. These differences
      were all highly significant (P<0.001). Uniform application of blood conserving
      techniques of burn wound excision result in highly significant reductions in
      blood product exposure without sacrifice of clinical outcomes.

PMID- 11311522
TI  - Life threatening burn injuries on holidays: problems of primary care, homeland
      referral and treatment at a domestic burn centre.
AB  - Life threatening burn injuries during vacations abroad raise special problems.
      Depending on the infrastructure of the country, adequate medical care can be
      delayed and communication between the patient and the medical staff is frequently
      impossible due to language barriers. Often the patient finds himself in a
      critical condition, isolated from supporting relatives and financial difficulties
      may occur. By summarising three cases referred to our centre, we aim to emphasise
      particularities of the primary management of burned victims at foreign hospitals,
      their transport, and following therapy at a domestic burn unit. Primary shock
      treatment and vital surgical interventions, e.g. escharotomy or treatment of the
      concomitant trauma, are subject to the facility of the hosting country. After
      management of the acute phase and initiation of local wound treatment, the next
      step should be to stabilise and prepare the patient for transport. Aeromedical
      transportation with physician attendency, as well as contact with a domestic burn
      centre can be established via responsible organisations. At the domestic
      hospital, every burn victim from abroad deserves special attention. Wound
      colonisation with different bacterial species or fungi than the usual spectrum of
      the centre and the risk of crossinfections should be taken in account of the
      treating medical team. An structure plan for appropriate and continuing surgical
      treatment is necessary to prevent deterioration of the patient's condition and to
      optimise wound closure with autologous skin grafts or allogenic materials.

PMID- 11311523
TI  - Reconstruction of a full-thickness defect of the chest wall caused by friction
      burn using a combined myocutaneous flap of teres major and latissimus dorsi
      muscles.
AB  - This report describes the therapeutic course of a case of deep burns caused by
      friction heat generated over a long contact time by a rotating tractor wheel. The
      burn was accompanied by a full-thickness defect of the chest wall, which we
      treated with a combined myocutaneous flap of teres major and latissimus dorsi
      muscles with a large skin flap. Our therapeutic concept of this case is
      discussed. Based on the postoperative course of this case, we think a combined
      myocutaneous flap of teres major and latissimus dorsi muscles with two nourishing
      vessels as an alternative is a very useful, safe, and secure method for the
      treatment of cases with axillary damages which require one-stage and stable
      reconstruction, like our patient.

PMID- 11311524
TI  - Onychocryptosis-phenol burn fiasco.
AB  - Ingrowing toenails, onychocryptosis, are a common condition that can be treated
      conservatively or surgically. Conservative treatment often fails necessitating
      operative intervention. Surgical treatments include wedge resection, Zadik's
      procedure and nail removal with ablation of the germinal matrix by phenol. The
      following report describes a 15-year-old male footballer who sustained burns
      following phenol treatment, resulting in amputation of his left great toe, as
      well as suggestions to avoid any similar complications.

PMID- 11311525
TI  - Prolonged intermittent hydrotherapy and early tangential excision in the
      treatment of an extensive strong alkali burn.
AB  - It is well known that the first step in the treatment of cutaneous strong alkali
      burn is very early and persistent washing of the site of injury with large
      volumes of water. However, ideal duration and the technique of hydrotherapy has
      not yet been established. Besides hydrotherapy, tangential excision of the
      injured skin might prevent further tissue damage if it is performed early enough.
      We report the treatment of a 36-year-old male who sustained 53% body surface area
      (BSA) cutaneous burn due to caustic soda (NaOH). Prolonged intermittent
      hydrotherapy, early tangential excision and autografting of the injured skin are
      the keys for the proper management of extensive strong alkali burn.

PMID- 11311526
TI  - Autoradiographic studies using L-[(14)C]DOPA and L-DOPA reveal regional Na(+)
      dependent uptake of the neurotransmitter candidate L-DOPA in the CNS.
AB  - We previously proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a
      neurotransmitter in the CNS. Receptor and transporter molecules for L-DOPA,
      however, have not been determined. In the present study, in order to localize the
      uptake sites of L-DOPA in the CNS, we performed autoradiographic uptake studies
      using L-[14C]DOPA and L-[3H]DOPA in the uptake study on rat brain slice
      preparations, and further analyzed the properties of L-DOPA uptake. Image
      analysis of the L-[14C]DOPA autoradiogram showed a unique heterogeneous
      distribution of uptake sites in the brain. The intensity was relatively high in
      the cerebral cortex, the hypothalamus, the cerebellum and the hippocampus, while
      the density was moderate or even low in the striatum and the substantia nigra. L
      DOPA and phenylalanine, but not dopamine (10mM) were able to almost completely
      inhibit the uptake of L-[14C]DOPA to basal levels. Microautoradiographic studies
      using L-[3H]DOPA revealed accumulation of dense grains in the median eminence,
      the supraoptic nucleus of the hypothalamus, the cerebral cortex (layer I) and the
      hippocampus. In the cerebellum, grains formed in clusters surrounding the
      Purkinje cells. This grain accumulation was concluded to be in Bergmann glial
      cells, since the morphological pattern of grain accumulation was similar to that
      of the immunoreactivity of the glutamate aspartate transporter, a marker protein
      for Bergmann glial cells. In the hippocampus, the grain density significantly
      decreased under Na(+)-free conditions. In addition, grain density also decreased
      in the absence of Cl(-). In contrast, grains in the choroid plexus and the
      ependymal cell layer, were not affected by the absence of Na(+). These findings
      indicated that the uptake of L-DOPA occurs via various types of large neutral
      amino acid transport mechanisms. It appears that neuronal and/or glial cells,
      which take up L-DOPA in a Na(+)-dependent manner, exist in the CNS. Our finding
      further supports the concept that L-DOPA itself may act as a neurotransmitter or
      neuromodulator.

PMID- 11311527
TI  - Subcellular localization of a glutathione-dependent dehydroascorbate reductase
      within specific rat brain regions.
AB  - Recently, we described the occurrence of a dehydroascorbate reductase within the
      rat CNS. This enzyme regenerates ascorbate after it is oxidized during normal
      aerobic metabolism. In this work, we describe the neuronal compartmentalization
      of the enzyme, using transmission electron microscopy of those brain areas in
      which the enzyme was most densely present when observed under light microscopy.
      In parallel biochemical studies, we performed immunoblotting and measured the
      enzyme activity of the cytoplasm and different nuclear fractions. Given the
      abundance of ascorbate in the caudate-putamen, we focused mostly on the
      occurrence of dehydroascorbate reductase at the striatal subcellular level. We
      also studied cerebellar Purkinje cells, hippocampal CA3 pyramidal cells and giant
      neurons in the magnocellular part of the red nucleus. In addition to neurons,
      immunolabeling was found in striatal endothelial cells, in the basal membrane of
      blood vessels and in perivascular astrocytes. In neuronal cytosol, the enzyme was
      observed in a peri-nuclear position and on the nuclear membrane. In addition, in
      both the striatum and the cerebellum, we found the enzyme within myelin sheets.
      Dehydroascorbate reductase was also present in the nucleus of neurons, as further
      indicated by measuring enzyme activity and by immunoblotting selected nuclear
      fractions. Immunocytochemical labeling confirmed that the protein was present in
      isolated pure nuclear fractions. Given the great amount of free radicals which
      are constantly generated in the CNS, the discovery of a new enzyme with
      antioxidant properties which translocates into neuronal nuclei appears to be a
      potential starting point to develop alternative strategies in neuroprotection.

PMID- 11311528
TI  - Maternal separation and social isolation modulate the postnatal development of
      synaptic composition in the infralimbic cortex of Octodon degus.
AB  - We analysed the influence of preweaning periodic maternal separation followed by
      postweaning chronic social isolation on the development of synaptic composition
      in the infralimbic cortex of Octodon degus, a South American species formerly
      classified as a caviomorph rodent but now considered to belong to Lagomorpha
      (rabbits). Three groups of animals were analysed: (1) control pups which remained
      undisturbed with their families; (2) pups which were exposed to individual
      periodic maternal deprivation [postnatal day 1 (P1) until P21], followed by
      social isolation (P22 until P45); and (3) pups which were handled daily without
      being removed from the families (P1 until P21) and thereafter remained
      undisturbed with the family (P22 until P45). The mean synaptic density and mean
      projected height of synapses were quantified using the "dissector" method. In the
      deprived group, significantly higher (up to 137.8%) mean synaptic densities were
      found in layer II of the infralimbic cortex compared to normal control animals.
      In handled pups, asymmetric shaft synapses were significantly decreased (down to
      54%) compared to the control group.These results indicate that early postnatal
      changes in the socio-emotional environment change the number of synaptic
      connections in the infralimbic cortex. Since this subregion of the medial
      prefrontal cortex is involved in a variety of emotional behaviors and plays a
      role in associative learning tasks, these environmentally induced synaptic
      changes may be indicative, and perhaps the cause, of alterations of behavioral
      and cognitive capacities.

PMID- 11311529
TI  - Inhibition of large-conductance Ca(2+)-activated K(+) channels in hippocampal
      neurons by toosendanin.
AB  - The effect of toosendanin, a selective presynaptic blocker and effective
      antibotulismic agent, on large-conductance Ca(2+)-activated K(+) channels was
      studied in inside-out patches of pyramidal neurons freshly isolated from the
      hippocampal CA1 region of the rat. Toosendanin (1 x 10(-6)g/ml approximately 1 x
      10(-4)g/ml) was found to inhibit large-conductance Ca(2+)-activated K(+) channels
      by reducing its open probability significantly in a concentration-dependent
      manner, although the effective concentration of toosendanin was lower in a
      symmetrical K(+) (150 mM) solution than under asymmetrical conditions (changing
      K(+) concentration in pipette solution to 5mM). The action was partially
      reversible by washing. By decreasing the slow open time constant, toosendanin
      shortened the open dwell time of large-conductance Ca(2+)-activated K(+) channels
      in a dose-dependent manner. A dose-dependent reduction of unitary current
      amplitude of the channel was detected after toosendanin perfusion. On elevating
      the intracellular free calcium concentration from 1 to 10 microM, a similar
      effect on large-conductance Ca(2+)-activated K(+) channels by toosendanin was
      also observed, but its efficacy was diminished. These results show that
      toosendanin inhibits large-conductance Ca(2+)-activated K(+) channels in
      hippocampal neurons by reducing the open probability and unitary current
      amplitude of the channel, and that Ca(2+) interferes with the effect. These data
      provide an explanation for toosendanin-induced facilitation of neurotransmitter
      release and the antibotulismic effect of the drug.

PMID- 11311530
TI  - Evidence of functional vitamin D receptors in rat hippocampus.
AB  - The steroid hormone vitamin D has important biological roles in calcium
      transport, cell growth, and cell differentiation. Its cellular activities are
      mediated by high affinity interaction with the vitamin D receptor. In brain,
      autoradiographic, immunohistologic, and messenger RNA expression studies
      implicate a number of neuronal systems, including the hippocampus, as potential
      targets of vitamin D. However, cellular distribution and protein expression, and
      binding of the receptor to vitamin D response elements have yet to be established
      in hippocampus. This investigation was undertaken to characterize the vitamin D
      receptor in rat hippocampus with western blot, immunocytochemistry, and gel shift
      analyses. The presence of the receptor protein in hippocampus extracts was
      revealed with western blotting using an anti-rat vitamin D receptor antiserum. In
      vivo and in vitro immunocytochemical results confirmed the presence of vitamin D
      receptor in neuronal and glial cells. In the hippocampus, the receptor was
      localized in pyramidal and granule cell layers, CA1, CA2, and CA3 subfields and
      in the dentate gyrus. Double labeling for the vitamin D receptor and glial
      fibrillary acidic protein revealed that glia also expressed the receptor protein.
      Gel shift analyses evaluated with the murine osteopontin vitamin D response
      element indicated a specific, bound receptor-containing complex from hippocampal
      extracts. Altogether, these findings clearly document the localization of vitamin
      D receptor in rat hippocampus and that hippocampus contains vitamin D receptors
      capable of specifically binding to DNA. In combination with reports of a
      neuroprotective role for vitamin D in hippocampal cell survival, these data
      suggest that the endogenous vitamin D receptor may mitigate processes related to
      cellular homeostasis, perhaps through a calcium buffering mechanism.

PMID- 11311531
TI  - Dexamethasone induces limited apoptosis and extensive sublethal damage to
      specific subregions of the striatum and hippocampus: implications for mood
      disorders.
AB  - It has been shown previously that the synthetic corticosteroid dexamethasone
      induces apoptosis of granule cells in the dentate gyrus and striatopallidal
      neurons in the dorsomedial caudate-putamen. We investigated whether or not
      dexamethasone can induce damage to other neuronal populations. This issue was
      addressed using OX42 immunohistochemistry to visualise activated microglia and
      thereby gauge the extent of dexamethasone-induced neuronal death. A single dose
      of dexamethasone (20mg/kg, i.p.) administered to young male Sprague-Dawley rats
      induced a strong microglial reaction which was restricted to the striatum, the
      dentate gyrus and all of the CA subfields of the hippocampus. Some OX42
      immunoreactive cells were also seen in the lateral septal nucleus. Subsequent
      quantitative analysis of silver/methenamine-stained sections confirmed that acute
      administration of dexamethasone induced apoptosis in the striatum and all regions
      of the hippocampus at doses as low as 0.7mg/kg. In contrast, dexamethasone failed
      to induce apoptosis in the lateral septal nucleus at doses up to 20mg/kg. The
      levels of dexamethasone-induced striatal and hippocampal apoptosis were
      attenuated by pretreatment with the corticosteroid receptor antagonist RU38486
      (Mifepristone), which implies that the cell death was mediated by a
      corticosteroid receptor-dependent process. We further determined whether
      dexamethasone induced sublethal damage to neurons by quantifying reductions in
      the number of microtubule-associated protein-2-immunoreactive striatal and
      hippocampal cells following injection of the corticosteroid. Dexamethasone
      induced dramatic decreases in the striatum, with the dorsomedial caudate-putamen
      being particularly affected. Similar damage was seen in the hippocampus, with the
      dentate gyrus and CA1 and CA3 subfields being particularly vulnerable.Equivalent
      corticosteroid-induced neuronal damage may occur in mood disorders, where the
      levels of endogenous corticosteroids are often raised. Corticosteroid-induced
      damage of striatal and hippocampal neurons may also account for some of the
      cognitive deficits seen following administration of the drugs to healthy
      volunteers.

PMID- 11311532
TI  - Prenatal glucocorticoid programming of brain corticosteroid receptors and
      corticotrophin-releasing hormone: possible implications for behaviour.
AB  - Glucocorticoids may underlie the association between low birth weight and adult
      disorders such as hypertension, type 2 diabetes and affective dysfunction. We
      investigated the behavioural and molecular consequences of two paradigms of
      prenatal dexamethasone administration in rats. Rats received dexamethasone (100
      microg/kg per day) throughout pregnancy (DEX1-3), in the last third of pregnancy
      only (DEX3) or vehicle. Both dexamethasone treatments reduced birth weight, only
      DEX1-3 offspring had reduced body weight in adulthood. In adult offspring, both
      prenatal dexamethasone paradigms reduced exploratory behaviour in an open field.
      In contrast, only DEX3 reduced exploration in an elevated plus-maze and impaired
      behavioural responses and learning in a forced-swim test. This behavioural
      inhibition may reflect increased baseline corticotrophin-releasing hormone mRNA
      levels (30% higher) in the central nucleus of the amygdala in both dexamethasone
      exposed groups. Adult DEX3 offspring also showed increased corticotrophin
      releasing hormone mRNA with unaltered glucocorticoid receptor mRNA in the
      hypothalamic paraventricular nucleus and reduced hippocampal glucocorticoid- and
      mineralocorticoid receptor mRNA expression, suggesting reduced hippocampal
      sensitivity to glucocorticoid suppression of the stress axis. In contrast, DEX1-3
      rats had no changes in hippocampal corticosteroid receptors, but showed increased
      mRNA levels for both receptors in the basolateral nucleus of the amygdala. From
      this data we suggest that prenatal glucocorticoid exposure programs behavioural
      inhibition perhaps via increased amygdalar corticotrophin-releasing hormone
      levels, while DEX3 also impairs coping and learning in aversive situations,
      possibly via altered hippocampal corticosteroid receptor levels. Overexposure to
      glucocorticoids, especially late in gestation, may explain the link between
      reduced early growth and adult affective dysfunction.

PMID- 11311533
TI  - Arrival of afferents and the differentiation of target neurons: studies of
      developing cholinergic projections to the dentate gyrus.
AB  - This study examined the relationship between the development of cholinergic axons
      originating from the septum and a group of their target cells, the granule cells
      of the dentate gyrus of the rat. Acetylcholinesterase histochemistry was used to
      identify septal cholinergic afferents to the dentate gyrus; parallel studies used
      anterograde movement of a carbocyanine dye to label the septal projections.
      Septal cholinergic axons are present in the molecular layer of the internal blade
      of the dentate gyrus shortly after birth, but these axons do not reach the
      external blade until several days later. Results demonstrate that
      acetylcholinesterase positive septal axons grow into the external blade of the
      dentate gyrus only after the recently generated granule cells have coalesced to
      form a clearly defined layer. Results from studies using in situ hybridization
      techniques demonstrate that dentate gyrus granule cells express messenger RNAs
      for brain derived neurotrophic factor and for neurotrophic factor 3 shortly after
      formation of the granule cell layer. Ingrowth of septal cholinergic axons follows
      two days after the formation of the external blade of the dentate gyrus and the
      expression of neurotrophin messenger RNAs by the dentate granule cells. These
      data support the hypothesis that target cell development is a prerequisite for
      attracting the ingrowth of septal afferent axons.

PMID- 11311534
TI  - GABA promotes survival but not proliferation of parvalbumin-immunoreactive
      interneurons in rodent neostriatum: an in vivo study with stereology.
AB  - Amino-acid neurotransmitters regulate a wide variety of developmental processes
      in the mammalian CNS including neurogenesis, cell migration, and apoptosis. In
      order to investigate the role of GABA in early development of forebrain
      interneurons, we determined the survival of parvalbumin-immunoreactive GABAergic
      interneurons in the adult rat striatum following prenatal exposure to either
      GABA(A) receptor agonist or antagonist. Unbiased stereology was used to quantify
      parvalbumin-immunoreactive neuron number in the neostriatum of adult rats exposed
      to the drugs in utero, and the results were compared to pair-fed or vehicle
      controls. Embryos were exposed to the GABA(A) antagonist (bicuculline) or agonist
      (muscimol) during previously defined proliferative or post-proliferative periods
      for parvalbumin-immunoreactive interneurons. Unbiased stereology using the
      optical fractionator was used to estimate the total number of parvalbumin
      immunoreactive neurons in neostriatum of experimental and control rats. No
      significant alteration in parvalbumin-immunoreactive neuron number was observed
      in rats treated with either bicuculline (1 or 2mg/kg/day) or muscimol
      (1mg/kg/day) during the proliferative phase. Administration of bicuculline during
      the post-proliferative phase significantly reduced parvalbumin-immunoreactive
      neuron number in the neostriatum. A concomitant decrease in neostriatal volume
      was also observed, suggesting that the effect is not restricted to parvalbumin
      immunoreactive interneurons. Positional analysis revealed loss of normal regional
      distribution gradients for parvalbumin-immunoreactive neurons in neostriatum of
      rats exposed to bicuculline in the embryonic post-proliferative phase. This data
      collectively suggests that GABA promotes survival but not proliferation of
      parvalbumin-immunoreactive progenitors. GABA may also promote migration of
      subpopulations of interneurons that ultimately populate the ventral
      telencephalon.

PMID- 11311535
TI  - Locomotor activity induced by the non-competitive N-methyl-D-aspartate
      antagonist, MK-801: role of nucleus accumbens efferent pathways.
AB  - We have recently shown that focal administration of dizocilpine hydrogen maleate
      (MK-801, a non-competitive N-methyl-D-aspartate antagonist) within the nucleus
      accumbens increases locomotor activity in a dopamine-independent manner. The
      purpose of this study was to investigate the neural network underlying locomotor
      stimulation induced by N-methyl-D-aspartate receptor blockade in the accumbens.
      In the first experiment, we examined the effect of different doses (1, 5 and 25
      nmol) of the active and inactive enantiomers of the N-methyl-D-aspartate
      antagonist, (+)- and (-)-MK-801, respectively, focally administered in the
      nucleus accumbens. Only the active enantiomer induced a significant increase in
      locomotor activity; furthermore, the effect induced by the two highest doses of
      (+)-MK-801 was significantly different from that induced by (-)-MK-801. In the
      second part of the study, we performed ibotenic acid lesions to the major output
      nuclei of the accumbens, the ventral pallidum, mediodorsal thalamus,
      ventrolateral/ventromedial thalamus and pedunculopontine tegmental nucleus, to
      observe their effect on locomotor activity induced by focal (+)-MK-801 (25 nmol)
      administration into the accumbens. None of the lesions had any effect on
      spontaneous locomotor activity. Hyperactivity induced by accumbens MK-801
      administrations was unaffected by ibotenic acid lesions of the pedunculopontine
      tegmental nucleus, while lesions of the mediodorsal thalamus induced only a
      partial inhibition. In contrast, ibotenic acid lesions of the ventral pallidum
      and ventrolateral/ventromedial thalamus completely blocked the motor response
      induced by accumbens MK-801. These data indicate that the intact mediodorsal
      thalamus, which has been proposed as a part of the loop that relays accumbens
      information to the prefrontal cortex, does not seem to be a structure of primary
      importance in MK-801 locomotor activity. On the contrary, the motor nuclei of the
      thalamus appear to play a more relevant role, suggesting that different neural
      substrates may mediate dopamine and glutamate functional output from the nucleus
      accumbens.

PMID- 11311536
TI  - GABA(A) agents injected into the ventral pallidum differentially affect
      dopaminergic pivoting and cholinergic circling elicited from the shell of the
      nucleus accumbens.
AB  - The ability of GABA(A) receptors in the ventral pallidum to modulate shell
      specific behavior was studied. Injections of the non-selective acetylcholine
      receptor agonist, carbachol (5 microg), into the shell of the nucleus accumbens
      elicited contraversive circling, namely turning marked by normal stepping; in
      contrast, injections of a mixture of dopamine D(1) (SKF 38393, 5 microg) and D(2)
      (quinpirole, 10 microg) receptor agonists into this brain structure elicited
      contraversive pivoting, namely turning marked by abnormal hindlimb stepping.
      Unilateral injections of the GABA(A) receptor agonist muscimol (10, 25 and 50 ng)
      into the ventral pallidum dose-dependently mimicked shell-specific circling,
      especially when given at a level +8.6mm anterior to the interaural line; this
      effect was GABA(A) receptor specific, because it was prevented by the GABA(A)
      receptor antagonist bicuculline (150 ng). Unilateral pallidal injections of a
      dose of muscimol that was ineffective per se (10 ng) abolished contraversive
      pivoting elicited by shell injections of dopamine receptor agonists; instead, it
      elicited moderate ipsiversive pivoting. Pallidal injections of bicuculline (150
      ng) replaced the contraversive pivoting elicited by dopamine receptor agonist
      with ipsiversive circling. In contrast, unilateral pallidal injections of 10 ng
      muscimol (anterior +8.6mm level) suppressed the contraversive circling elicited
      by shell injections of carbachol; instead, it elicited moderate ipsiversive
      pivoting. Pallidal injections of bicuculline (150 ng) produced short-lasting
      ipsiversive circling that was followed by contraversive pivoting. We conclude
      that the ventromedial portion of the ventral pallidum contains GABA(A) receptors
      that are crucial for the transmission of information from the shell of the
      nucleus accumbens via the ventral pallidum towards other brain structures; this
      holds especially for information about shell-specific circling elicited by
      carbachol. The same portion of the ventral pallidum also contains GABA(A)
      receptors that control the transfer of information from the nucleus accumbens
      towards structures outside the ventral pallidum; this holds especially for
      information about shell-specific pivoting elicited by dopaminergic agonists.

PMID- 11311537
TI  - Involvement of pallidothalamic circuitry in working memory.
AB  - This study evaluated the capacity of mu-opioid and glutamate receptor agonists to
      differentially regulate the involvement of the GABAergic projection from the
      ventral pallidum to the mediodorsal thalamus in working memory and locomotor
      activity. Microinjection of either the ionotropic glutamate receptor agonist
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) or the mu agonist [D
      Ala(2),N-Me-Phe(4),Gly-ol(5)]enkephalin into the ventral pallidum of male Sprague
      Dawley rats produced a dose-dependent impairment in working memory, estimated
      using a forced delayed alternation task in a T-maze. Performance in a spatial
      discrimination task without delay was also impaired by glutamate, but not by mu
      receptor, stimulation. Involvement of the GABAergic projection from the ventral
      pallidum to the mediodorsal thalamus in mu-opioid-induced impairment of working
      memory was verified by showing that inhibiting GABA(B) receptors in the
      mediodorsal thalamus blocked the effect of [D-Ala(2),N-Me-Phe(4),Gly
      ol(5)]enkephalin in the ventral pallidum. Similarly, either glutamate or mu
      opioid receptor stimulation in the ventral pallidum elicited motor activity, and
      the motor stimulant effect of the mu agonist was blocked, while that of AMPA is
      not affected by GABA(B) receptor blockade in the mediodorsal thalamus.
      Distinction between mu and glutamate receptor stimulation was further revealed by
      the fact that stimulating mu receptors in the ventral pallidum caused a dose
      dependent reduction in extracellular GABA levels, while AMPA was without effect
      on GABA in the ventral pallidum. These data indicate that stimulating mu-opioid
      receptors reduces GABAergic tone in the ventral pallidum, which increases
      activity in the GABAergic projection to the mediodorsal thalamus, thereby
      impairing working memory. Moreover, it is hypothesized that mu receptors in the
      ventral pallidum gate the recruitment of working memory into ongoing behavioral
      activity.

PMID- 11311538
TI  - Mitral cell presynaptic Ca(2+) influx and synaptic transmission in frog amygdala.
AB  - Dextran-conjugated Ca(2+) indicators were injected into the accessory olfactory
      bulb of frogs in vivo to selectively fill presynaptic terminals of mitral cells
      at their termination in the ipsilateral amygdala. After one to three days of
      uptake and transport, the forebrain hemisphere anterior to the tectum was removed
      and maintained in vitro for simultaneous electrophysiological and optical
      measurements. Ca(2+) influx into these terminals was compared to synaptic
      transmission between mitral cells and amygdala neurons under conditions of
      reduced Ca(2+) influx resulting from reduced extracellular [Ca(2+)], blockade of
      N- and P/Q-type channels, and application of the cholinergic agonist carbachol.
      Reducing extracellular [Ca(2+)] had a non-linear effect on release; release was
      proportional to Ca(2+) influx raised to the power of approximately 3.6, as
      observed at numerous other synapses. The N-type Ca(2+) channel blocker, omega
      conotoxin-GVIA (1 microM), blocked 77% of Ca(2+) influx and 88% of the
      postsynaptic field potential. The P/Q-type Ca(2+) channel blocker, omega-agatoxin
      IVA (200 nM), blocked 19% of Ca(2+) influx and 25% of the postsynaptic field,
      while the two toxins combined to block 92% of Ca(2+) influx and 97% of the
      postsynaptic field. The relationship between toxin blockade of Ca(2+) influx and
      synaptic transmission was therefore only slightly non-linear; release was
      proportional to Ca(2+) influx raised to the power approximately 1.4. Carbachol
      (100 microM) acting via muscarinic receptors had no effect on the afferent
      volley, but rapidly and reversibly reduced Ca(2+) influx through both N- and P/Q
      type channels by 51% and postsynaptic responses by 78%, i.e. release was
      proportional to Ca(2+) raised to the power approximately 2.5. The weak dependence
      of release on changes in Ca(2+) when channel toxins block channels suggests
      little overlap between Ca(2+) microdomains from channels supporting release or
      substantial segregation of channel subtypes between terminals. The
      proportionately greater reduction of transmission by muscarinic receptors
      compared to Ca(2+) channel toxins suggests that they directly affect the release
      machinery in addition to reducing Ca(2+) influx.

PMID- 11311539
TI  - Directional modulation of visual responses of pretectal neurons by accessory
      optic neurons in pigeons.
AB  - The nucleus lentiformis mesencephali and the nucleus of the basal optic root in
      birds, homologous to the nucleus of the optic tract and the terminal nuclei of
      the accessory optic tract in mammals, are involved in optokinetic nystagmus. The
      present study provides the first electrophysiological evidence that reversible
      blockade of the pigeon nucleus of the basal optic root by lidocaine can change
      visual responsiveness of pretectal neurons in a direction-dependent manner.
      Thirty pretectal cells examined were classified as unidirectional (80%),
      bidirectional (10%) and omnidirectional (10%) cells according to their
      directional selectivity. Among the unidirectional cells, seven cells changed
      firing rates in all directions of motion, 11 changed visual responses only in the
      preferred directions and six others did not change their responsiveness during
      lidocaine. Most of the bidirectional cells changed firing rates in the
      temporonasal direction, and two-thirds of the omnidirectional cells showed these
      changes in all directions. Thirteen lidocaine administration sites were marked
      within the nucleus of the basal optic root and 19 recording sites were marked
      within the nucleus lentiformis mesencephali. This histological verification
      indicates that the effects of lidocaine blockade in the accessory optic nucleus
      on the directional selectivity and visual responsiveness of pretectal cells
      appear to be related, to some extent, to the location of drug injections in the
      nucleus of the basal optic root. This study has found that visual neurons in the
      nucleus of the basal optic root, which predominantly prefer vertical and backward
      motion, could modulate the directional selectivity and visual responsiveness of
      neurons in the nucleus lentiformis mesencephali, which mainly prefer horizontal
      motion. It is conceivable that both nuclei work together in coordination and in
      competition during optokinetic nystagmus.

PMID- 11311541
TI  - Ultrastructural analysis of ventrolateral periaqueductal gray projections to the
      A7 catecholamine cell group.
AB  - Stimulation of neurons in the ventrolateral periaqueductal gray produces
      antinociception that is mediated in part by pontine noradrenergic neurons.
      Previous light microscopic analysis provided suggestive evidence for a direct
      projection from neurons in the ventrolateral periaqueductal gray to noradrenergic
      neurons in the A7 cell group that innervate the spinal cord dorsal horn.
      Therefore, the present ultrastructural study used anterograde tracing combined
      with tyrosine hydroxylase immunoreactivity to provide definitive evidence that
      neurons in the ventrolateral periaqueductal gray form synapses with the somata
      and dendrites of noradrenergic neurons of the A7 cell group. Injections of the
      anterograde tracers biotinylated dextran amine or Phaseolus vulgaris
      leucoagglutinin into the ventrolateral periaqueductal gray of Sasco Sprague
      Dawley rats yielded a dense innervation in the region of the lateral pons
      containing the A7 cell group. Electron microscopic analysis of anterogradely
      labeled terminals (n=401) in the region of the A7 cell group indicated that
      approximately 10% of these formed plasmalemmal appositions to tyrosine
      hydroxylase-immunoreactive dendrites with no intervening astrocytic processes.
      About 23% of these were asymmetric synapses, 10% were symmetric synapses, and 67%
      did not exhibit clearly differentiated synaptic specializations. The majority of
      anterogradely labeled terminals (60%) formed plasmalemmal appositions with
      dendrites and somata that lacked detectable tyrosine hydroxylase
      immunoreactivity. About 35% of these were symmetric synapses, 9% were asymmetric
      synapses and 56% did not form synaptic specializations. Approximately 30% of all
      anterogradely labeled terminals displayed features characteristic of axo-axonic
      synapses.The present results provide direct ultrastructural evidence to support
      the hypothesis that the analgesia produced by stimulation of neurons in the
      ventrolateral periaqueductal gray is mediated, in part, by activation of spinally
      projecting noradrenergic neurons in the A7 catecholamine cell group.

PMID- 11311540
TI  - Pharmacology, distribution and development of muscarinic acetylcholine receptor
      subtypes in the optic tectum of Rana pipiens.
AB  - Visually evoked behaviors mediated by the frog optic tectum require cholinergic
      activity, but the receptor subtypes through which acetylcholine acts are not yet
      identified. Using quantitative autoradiography and scintillation spectrometry, we
      examined the binding of [3H]pirenzepine and [3H]AF-DX 384 in the laminated optic
      tectum of the frog. In mammalian systems, these substances bind excitatory (m1
      and m3 subtypes) and inhibitory (m2 and m4 subtypes) muscarinic acetylcholine
      receptors, respectively. Pharmacological analyses, including the use of specific
      muscarinic toxins, confirmed the subtype selectivity of the radioligands in the
      frog brain. Binding sites for [3H]pirenzepine were distinct from those for [3H]AF
      DX 384. In the adult tectum, [3H]pirenzepine demonstrated specific binding in
      tectal layers 5-9. [3H]Pirenzepine binding was also present in tadpoles as young
      as stage V, but all sampled stages of tadpole tectum had significantly less
      binding when compared to adults. Lesioning of the optic nerve had no effect on
      [3H]pirenzepine binding. Specific [3H]AF-DX 384 binding was found in all layers
      of the adult tectum. All sampled tadpole stages exhibited binding sites for
      [3H]AF-DX 384, but the densities of these sites were also significantly higher in
      adults than they were in developing stages. Short-term lesions of the optic nerve
      reduced [3H]AF-DX 384 binding in all tectal layers of the deafferented lobe when
      compared to the afferented one. Long-term lesions decreased [3H]AF-DX 384 sites
      in both lobes.These results indicate that multiple muscarinic acetylcholine
      receptor binding sites reside in the frog optic tectum at all stages of
      development, and their pharmacology resembles that of mammalian m1/m3, m2 and m4
      subtypes. Our data indicate that few, if any, of these receptors are likely to be
      located on retinal ganglion cell terminals. Furthermore, the expression of
      inhibitory muscarinic subtypes seems to be regulated by different mechanisms than
      that for excitatory subtypes.

PMID- 11311542
TI  - On the reduction of spontaneous and glutamate-driven spinocerebellar and
      spinoreticular tract neuronal activity during active sleep.
AB  - The present study was performed to provide evidence that dynamic neural processes
      underlie the reduction in dorsal spinocerebellar tract and spinoreticular tract
      neuron activity that occurs during active sleep. To ascertain the effect of local
      inhibition on the spontaneous and glutamate-evoked spike discharge of sensory
      tract neurons, preliminary control tests were performed during the state of quiet
      wakefulness, where GABA or glycine was co-administered in a sustained fashion
      during pulsatile release of glutamate to dorsal spinocerebellar tract (n=3) or
      spinoreticular tract (n=2) neurons. Co-administration of GABA or glycine also
      resulted in a significant marked suppression of spontaneous spike activity and
      glutamate-evoked responses of these cells. Extracellular recording experiments
      combined with juxtacellular application of glutamate were then performed on 20
      antidromically identified dorsal spinocerebellar tract and spinoreticular tract
      neurons in the chronic intact cat as a function of sleep and wakefulness. The
      glutamate-evoked activity of a group of 10 sensory tract neurons (seven dorsal
      spinocerebellar tract, three spinoreticular tract), which exhibited a significant
      decrease in their spontaneous spike activity during active sleep, was examined.
      Glutamate-evoked activity in these cells was significantly attenuated during
      active sleep compared with wakefulness. In contrast, the glutamate-evoked
      activity of a second group of eight sensory tract neurons (four dorsal
      spinocerebellar tract, four spinoreticular tract), which exhibited a significant
      increase in their spontaneous spike activity during active sleep, was not
      significantly altered in a state-dependent manner. These data indicate that,
      during natural active sleep, a dynamic neural process is engaged onto certain
      dorsal spinocerebellar tract and spinoreticular tract neurons, which in turn
      dampens sensory throughput to higher brain centers.

PMID- 11311543
TI  - Transgenic mice with neuronal overexpression of bcl-2 gene present navigation
      disabilities in a water task.
AB  - In the CNS, Bcl-2 is an antiapoptotic gene involved in the regulation of neuronal
      death. Transgenic mice overexpressing the human gene Bcl-2 (Hu-bcl-2 mice) showed
      delayed acquisition in two tasks requiring them to find a hidden platform
      starting from either a random or a constant starting location. The same mice were
      not deficient in another task requiring them to find a visible platform
      suggesting that the delay observed was not due to motor, visual or motivational
      deficits in the water. The delay observed in Hu-bcl-2 mice was more important in
      the random starting test in which the allocentric demand for navigation was
      stronger. The results suggested that allocentric navigation is particularly
      sensitive to abnormal CNS maturation following the overexpression of the bcl-2
      gene. The specific deficits (motor learning, fear-related behavior and
      allocentric navigation) observed in Hu-bcl-2 mice suggest that the regulation of
      developmental neuronal death is crucial for multisensorial learning and emotional
      behavior.

PMID- 11311544
TI  - Morphine tolerance and dependence in nociceptin/orphanin FQ transgenic knock-out
      mice.
AB  - It has been hypothesized that morphine tolerance and dependence in mice following
      chronic exposure may reflect increased compensatory activity of antiopioid
      systems. The endogenous peptide nociceptin/orphanin FQ has been shown to have
      anti-opioid effects, for example antagonizing morphine analgesia. Moreover,
      chronic morphine administration increases synthesis of the peptide, and morphine
      tolerance and dependence can be attenuated or reversed by antagonists and
      agonists of the nociceptin/orphanin FQ receptor, respectively. The present study
      seeks to confirm a role for nociceptin/orphanin FQ in opioid tolerance and
      dependence by comparing morphine ED(50) values and naloxone-precipitated
      withdrawal jumping in mice homozygous (knock-out) and heterozygous for a null
      mutation of the Npnc1 gene encoding the nociceptin/orphanin FQ propeptide, and
      their wild type littermates, following chronic morphine exposure. Relative to
      morphine-naive control mice, significant rightward shifts in the morphine dose
      response curve, resulting in increased morphine ED(50) values (approximately two
      to three-fold), was observed for all genotypes following three days of repeated
      systemic morphine injections. However, no differences between genotypes in the
      magnitude of tolerance were observed. In contrast, knock-out mice displayed
      significantly increased naloxone-precipitated withdrawal jumping relative to
      heterozygous and wild-type mice following implantation with a morphine pellet
      (25mg) for 72h. Use of nociception/orphaninFQ transgenic knock-out mice thus
      demonstrate the differential involvement of nociceptin/orphanin FQ in morphine
      tolerance and dependence.

PMID- 11311545
TI  - Neuronal injury-induced expression and release of apolipoprotein E in mixed
      neuron/glia co-cultures: nuclear factor kappaB inhibitors reduce basal and lesion
      induced secretion of apolipoprotein E.
AB  - In order to better delineate the intracellular signaling pathways underlying
      glial apolipoprotein E (apoE) expression and release, we have characterized an in
      vitro model of induction of glial apoE production induced by neuronal death.
      Exposure of mixed fetal cortical neuron/glia co-cultures to the neurotoxin N
      methyl-D-aspartate results in increased apoE expression and release in a time-
      and concentration-dependent manner. Increased expression of apoE messenger RNA
      precedes the increase in intracellular apoE, followed by accumulation of the
      holoprotein in the culture medium. Neuronal injury induced by N-methyl-D
      aspartate is accompanied by a reactive astrogliosis as measured by an increase in
      glial fibrillary acidic protein messenger RNA and protein at 48 and 72h post
      lesion, respectively. A similar microgliosis was observed using the microglial
      marker ED-1. Neuronal injury-induced glial apoE secretion is attenuated by the
      nuclear factor kappaB inhibitors, aspirin, Bay 11-7082 and MG-132, suggesting
      that this transcription factor is involved in both constitutive and induced glial
      apoE expression. The present data show that up-regulation of apoE is an early
      event in the glial activation triggered by neurodegeneration in vitro and that
      activation of nuclear factor kappaB directly or indirectly mediates the increase
      in apoE expression.

PMID- 11311546
TI  - Changes in axonal physiology and morphology after chronic compressive injury of
      the rat thoracic spinal cord.
AB  - The spinal cord is rarely transected after spinal cord injury. Dysfunction of
      surviving axons, which traverse the site of spinal cord injury, appears to
      contribute to post-traumatic neurological deficits, although the underlying
      mechanisms remain unclear. The subpial rim frequently contains thinly myelinated
      axons which appear to conduct signals abnormally, although it is uncertain
      whether this truly reflects maladaptive alterations in conduction properties of
      injured axons during the chronic phase of spinal cord injury or whether this is
      merely the result of the selective survival of a subpopulation of axons. In the
      present study, we examined the changes in axonal conduction properties after
      chronic clip compression injury of the rat thoracic spinal cord, using the
      sucrose gap technique and quantitatively examined changes in the morphological
      and ultrastructural features of injured axonal fibers in order to clarify these
      issues. Chronically injured dorsal columns had a markedly reduced compound action
      potential amplitude (8.3% of control) and exhibited significantly reduced
      excitability. Other dysfunctional conduction properties of injured axons included
      a slower population conduction velocity, a longer refractory period and a greater
      degree of high-frequency conduction block at 200 Hz. Light microscopic and
      ultrastructural analysis showed numerous axons with abnormally thin myelin
      sheaths as well as unmyelinated axons in the injured spinal cord. The ventral
      column showed a reduced median axonal diameter and the lateral and dorsal columns
      showed increased median diameters, with evidence of abnormally large swollen
      axons. Plots of axonal diameter versus myelination ratio showed that post-injury,
      dorsal column axons of all diameters had thinner myelin sheaths. Noninjured
      dorsal column axons had a median myelination ratio (1.56) which was within the
      optimal range (1.43-1.67) for axonal conduction, whereas injured dorsal column
      axons had a median myelination ratio (1.33) below the optimal value. These data
      suggest that maladaptive alterations occur postinjury to myelin sheath thickness
      which reduce the efficiency of axonal signal transmission.In conclusion,
      chronically injured dorsal column axons show physiological evidence of
      dysfunction and morphological changes in axonal diameter and reduced myelination
      ratio. These maladaptive alterations to injured axons, including decrease in
      myelin thickness and the appearance of axonal swellings, contribute to the
      decreased excitability of chronically injured axons. These results further
      clarify the mechanisms underlying neurological dysfunction after chronic
      neurotrauma and have significant implications regarding approaches to augment
      neural repair and regeneration.

PMID- 11311547
TI  - Presynaptic localization of the small conductance calcium-activated potassium
      channel SK3 at the neuromuscular junction.
AB  - Small conductance, calcium-activated potassium channels (SK channels) are present
      in most neurons, in denervated muscles and in several non-excitable cell types.
      In excitable cells SK channels play a fundamental role in the generation of the
      afterhyperpolarization which follows an action potential, thereby modulating
      neuronal firing and regulating excitability. To date, three channel subunits (SK1
      3) have been cloned from mammalian brain. Since SK3 only has been shown to be
      expressed in muscles upon denervation, this channel may be involved in
      hyperexcitability and afterhyperpolarization observed in muscle cells in the
      absence of the nerve. Using confocal microscopy and SK3 specific antibodies, we
      demonstrate that SK3 immunoreactivity is present at the rat neuromuscular
      junction in denervated but also in innervated muscles. In denervated muscle
      fibers, SK3 is localized in the extrajunctional as well as the junctional plasma
      membrane, where it appears to be less abundant in the acetylcholine receptor-rich
      domains, corresponding to the crests of the postsynaptic folds. In innervated
      muscles, SK3 is not detectable in the muscle fiber but is present at the
      neuromuscular junction and seems to be localized presynaptically in the motor
      nerve terminals. Axonal accumulation of SK3 immunoreactivity occurs above and
      below a ligature of rat sciatic nerve, indicating that the SK3 protein is
      transported in both directions along the axons of the motor neurons. During rat
      development SK3 immunoreactivity is not found at the neuromuscular junction until
      day 35 of postnatal development when SK3 first appears in the motor neuron
      terminals. These results indicate that SK3 channels are components of the
      presynaptic compartment in the mature neuromuscular junction, where they may play
      an important regulatory role in synaptic transmission.

PMID- 11311548
TI  - Comparison of the effects of neurokinin-3 receptor blockade on two forms of slow
      synaptic transmission in myenteric AH neurons.
AB  - AH neurons are intrinsic sensory neurons of the intestine that exhibit two types
      of slow synaptic event: slow excitatory postsynaptic potentials which increase
      their excitability for about 2-4 min, and sustained slow postsynaptic excitation
      which can persist for several hours, and may be involved in long-term changes in
      the sensitivity of the intestine to sensory stimuli. The effects of the
      neurokinin-3 tachykinin receptor antagonist, SR142801, on these two types of
      synaptic event in AH neurons of the myenteric ganglia of guinea-pig small
      intestine were compared. Slow excitatory postsynaptic potentials were evoked by
      stimulation of synaptic inputs at 10-20 Hz for 1s, and sustained slow
      postsynaptic excitation was evoked by stimulation of inputs at 1Hz for 4 min.
      SR142801 (1microM) reduced the amplitude of the slow excitatory postsynaptic
      potential to 26% of control, and also reduced the increase in input resistance
      and the extent of anode break excitation associated with the slow excitatory
      postsynaptic potential. In contrast, SR142801 did not reduce the increase in
      excitability, the increase in input resistance or the depolarisation that occur
      during the sustained slow postsynaptic excitation. SR142801 did not change the
      resting membrane potential or the resting input resistance. We conclude that
      tachykinins, acting through neurokinin-3 receptors, are involved in the
      generation of the slow excitatory postsynaptic potential, but not in the
      sustained slow postsynaptic excitation, and that the release of transmitters from
      synaptic inputs to AH neurons is frequency coded.

PMID- 11311549
TI  - Intracellular injection of synapsin I induces neurotransmitter release in C1
      neurons of Helix pomatia contacting a wrong target.
AB  - The contact with the postsynaptic target induces structural and functional
      modifications in the serotonergic cell C1 of Helix pomatia. In previous studies
      we have found that the presence of a non-physiological target down-regulates the
      number of presynaptic varicosities formed by cultured C1 neurons and has a strong
      inhibitory effect on the action potential-evoked Ca(2+) influx and
      neurotransmitter release at C1 terminals. Since a large body of experimental
      evidence implicates the synapsins in the development and functional maturation of
      synaptic connections, we have investigated whether the injection of exogenous
      synapsin I into the presynaptic neuron C1 could affect the inhibitory effect of
      the wrong target on neurotransmitter release. C1 neurons were cultured with the
      wrong target neuron C3 for three to five days and then injected with either
      dephosphorylated or Ca(2+)/calmodulin-dependent protein kinase II-phosphorylated
      Cy3-labeled synapsin I. The subcellular distribution of exogenous synapsin I,
      followed by fluorescence videomicroscopy, revealed that only synapsin I
      phosphorylated by Ca(2+)/calmodulin-dependent protein kinase II diffused in the
      cytoplasm and reached the terminal arborizations of the axon, while the
      dephosphorylated form did not diffuse beyond the cell body. Evoked
      neurotransmitter release was measured during C1 stimulation using a freshly
      dissociated neuron B2 (sniffer) micromanipulated in close contact with the
      terminals of C1. A three-fold increase in the amplitude of the sniffer
      depolarization with respect to the pre-injection amplitude (190+/-29% increase,
      n=10, P<0.006) was found 5 min after injection of Ca(2+)/calmodulin-dependent
      protein kinase II-phosphorylated synapsin I that lasted for about 30 min. No
      significant change was observed after injection of buffer or dephosphorylated
      synapsin I. These data indicate that the presence of synapsin I induces a fast
      increase in neurotransmitter release that overcomes the inhibitory effect of the
      non-physiological target and suggest that the expression of synapsins may play a
      role in the modulation of synaptic strength and neural connectivity.

PMID- 11311550
TI  - Transcriptional regulation of the rat eIF4E gene in cardiac muscle cells: the
      role of specific elements in the promoter region.
AB  - Eukaryotic initiation factor 4E (eIF4E) binds to the 7-methylguanosine cap of
      mRNA and facilitates binding of mRNA to the 40 S ribosome, a rate-limiting step
      in translation initiation. The expression of eIF4E mRNA and protein increases
      during growth of cardiac muscle cells (cardiocytes) in vitro. To examine
      transcriptional regulation of the rat eIF4E gene, 2.1 kB of the rat eIF4E
      promoter region was cloned and the contribution of specific elements in
      regulating transcription was determined in primary cultures of rat cardiocytes
      and in a murine C(2)C(12) myoblast cell line. Sequence analysis of the rat eIF4E
      promoter revealed 80% sequence similarity with human eIF4E. A putative distal E
      box was found at -230 bp and a proximal E-box was located at -77 bp upstream of
      the transcription start site. Consensus AP-1 motifs were found at -839 and -901
      bp and designated as the proximal AP-1 site and distal AP-1 site, respectively.
      Transfection of reporter gene constructs into cardiocytes showed that deletion of
      the region between -633 and -318 bp produced a 3-fold increase in basal
      transcription as compared to the 2.1 kB eIF4E promoter construct. Further
      deletion of the distal E-box region had no effect on transcription as compared
      with the 2.1 kB promoter, but deletion of both E-boxes eliminated transcriptional
      activity. Similar results were obtained in C(2)C(12) myoblasts. To further
      investigate transcriptional regulation, point mutations were made in the 2.1 kB
      eIF4E promoter. Mutation of either the distal or proximal E-box had minimal
      effects on activity in either cell type, but mutation of the distal AP-1 site
      significantly reduced eIF4E promoter activity by 66+/-4% in cardiocytes. In
      C(2)C(12) myoblasts, mutating the distal AP-1 site reduced activity by 30+/-4% We
      conclude that both E-boxes are required for maximal basal activity of the eIF4E
      promoter, and that the distal AP-1 motif may activate transcription.

PMID- 11311551
TI  - The invertebrate growth factor/CECR1 subfamily of adenosine deaminase proteins.
AB  - Adenosine deaminase (ADA) catalyzes the hydrolysis of adenosine to inosine. Its
      lack determines severe combined immunodeficiency in mammals, possibly due to
      accumulation of extracellular adenosine, which induces apoptosis in lymphocytes
      (Franco et al., 1998). Thus, presence of normal levels of ADA leads to normal
      growth and proliferation of lymphocytes. Several vertebrate and microbial ADA
      amino-acid sequences are known, with substantial similarity to each other. On the
      other hand, there are invertebrate growth factors as well as a candidate gene for
      the human cat eye syndrome (CECR1) (Riazi et al., 2000. Genomics 64, 277-285),
      which share substantial similarity to each other, and also to ADA. In this study,
      we report the expression and ADA enzymatic activity of a cDNA from the salivary
      glands of Lutzomyia longipalpis, a blood-sucking insect, with substantial
      similarity to insect growth factors and to human CECR1. We also demonstrate the
      existence of a subfamily of the adenosine deaminase family characterized by their
      unique amino-terminal region. Both Drosophila melanogaster and humans have both
      types of adenosine deaminases. Results indicate that these invertebrate proteins
      previously annotated as growth factors, as well as the human CECR1 gene product,
      may exert their actions through adenosine depletion. The different roles played
      by each type of adenosine deaminase in humans and Drosophila remains to be fully
      investigated.

PMID- 11311552
TI  - Gene structure and enzymatic activity of mouse eosinophil-associated ribonuclease
      2.
AB  - Mouse eosinophil-associated ribonuclease-2 (mEAR-2) is one of a cluster of genes
      identified in the genome of the mouse Mus musculus that are highly divergent
      orthologs of the primate ribonucleases, eosinophil-derived neurotoxin (EDN) and
      eosinophil cationic protein (ECP). Northern analysis revealed expression of genes
      hybridizing to mEAR-2 in mouse lung, liver and spleen tissues. We obtained full
      length cDNA by hybridization screening of mouse eosinophil and lung cDNA
      libraries and by rapid amplification of cDNA ends (RACE) from liver, spleen and
      lung RNA. Using these methods we have isolated the 195 base pair (bp) 3'
      untranslated region (UTR) that includes a typical polyadenylation signal
      preceding a poly A tail and the 5' UTR which includes 63-71 bp and three distinct
      transcriptional start sites. Using unidirectional PCR we isolated a 361-bp 5'
      promoter region and delineated the intronic / exonic boundaries which include a
      non-coding exon 1, a single intron, and a coding exon 2, a structure that is
      typical of genes of the RNase A superfamily. Consensus sites for PU.1 and EoTF,
      both active as intronic enhancer elements of the gene encoding EDN, are also
      present in the intron of the gene encoding mEAR-2. The catalytic activity of
      recombinant baculovirus-derived mEAR-2 is similar to that of rhEDN from this
      source, with catalytic constants k(cat)/K(m)=5.6x10(6) M(-1) s(-1) and 10.5x10(6)
      M(-1) s(-1), respectively, against a standard yeast tRNA substrate. Sequence
      analysis of the non-coding regions and enzymatic characterization of the gene
      product provide further evidence indicating that mEAR-2 is a structural and
      functional ortholog of primate EDNs and ECPs.

PMID- 11311553
TI  - Involvement of yeast carboxy-terminal domain kinase I (CTDK-I) in transcription
      elongation in vivo.
AB  - Yeast cells lacking transcription elongation factor genes such as PPR2 (TFIIS)
      and ELP (Elongator) are viable and show deleterious phenotypes only when
      transcription is rendered less effective by RNA polymerase mutations or by
      decreasing nucleotide pools. Here we demonstrate that deletion of the CTK1 gene,
      encoding the kinase subunit of RNA polymerase II carboxy-terminal domain kinase I
      (CTDK-I), is synthetically lethal when combined with deletion of PPR2 or ELP
      genes. The inviability of ctk1 elp3 double mutants can be rescued by expression
      of an Elp3 mutant that has retained its ability to form the Elongator complex but
      has severely diminished histone acetyltransferase activity, suggesting that the
      functional overlap between CTDK-I and Elongator is in assembly of RNA polymerase
      II elongation complexes. Our results suggest that CTDK-I plays an important role
      in transcriptional elongation in vivo, possibly by creating a form of RNA
      polymerase that is less prone to transcriptional arrest.

PMID- 11311554
TI  - Cloning, transcription and chromosomal localization of the porcine whey acidic
      protein gene and its expression in HC11 cell line.
AB  - The whey acidic protein (WAP) is the major whey protein of rodent, rabbit and
      camel. Recently, it was identified in the milk of swine (Simpson et al., 1998. J.
      Mol. Endocrinol. 20, 27-35). In this paper, the cloning of the pig WAP cDNA and
      of bacterial artificial chromosome (BAC) construct containing the entire porcine
      WAP gene is reported. The comparison of the coding sequence of the pig WAP gene
      to rodent or lagomorph WAP sequence already published demonstrated that only exon
      sequences are partially conserved. The porcine WAP gene was localized on the
      subtelomeric region of the chromosome 18. The estimation of the expression of the
      swine WAP gene in the mammary gland from lactating animals revealed a high level
      of expression. In order to compare the expression level of the porcine WAP gene
      from the large genomic fragment which contained 70 kb downstream and 50 kb
      upstream the pig WAP gene or the smaller one (1 kb downstream and 2.4 kb
      upstream), these two genomic fragments were transfected in HC11 cell line. The
      BAC construct was expressed 15 times higher than the plasmid when reported to the
      integrated copy number. This report suggests that the HC11 cell line is a useful
      tool to identify the regulatory sequences of milk protein genes.

PMID- 11311555
TI  - Nested genomic structure of haploid germ cell specific haspin gene.
AB  - The haspin gene specifically expressed in haploid germ cells encodes a unique
      Ser/Thr protein kinase. We have cloned a mouse haspin genomic clone using cDNA as
      a probe. Sequencing data showed that the haspin gene was not interrupted by
      introns and was bordered by appropriate direct repeat. The transcription start
      site of the gene was not preceded by a TATA box. The whole transcription unit was
      located at an intron of integrin alphaM290 gene, and transcription direction of
      these two genes was different. Southern blotting analysis under stringent
      condition showed that haspin was a single gene. Phylogenetic analysis suggested
      that the diversion of haspin gene from other kinase family might be very ancient:
      the early stage of plant-fungus-animal split.

PMID- 11311556
TI  - The Haspin gene: location in an intron of the integrin alphaE gene, associated
      transcription of an integrin alphaE-derived RNA and expression in diploid as well
      as haploid cells.
AB  - Haspin is a serine/threonine kinase, recently identified in mice, that is thought
      to regulate cell cycle and differentiation of haploid germ cells. Here, the
      haspin gene is identified within an intron of the integrin alphaE gene.
      Transcription occurs from a bi-directional CpG island-associated promoter that
      also generates an alternatively spliced integrin alphaE derived RNA. Remarkably,
      the human and murine haspin genes lack introns, and have features of retroposons.
      The human haspin cDNA reveals that the human and murine proteins are 83%
      identical in the C-terminal kinase domain, but only 53% identical in the N
      terminal region. The haspin kinase domain has structural features that
      distinguish it from previously characterized proteins and suggest that haspin is
      a member of a new family of protein kinases. Although formerly thought to be
      expressed selectively in the testes, haspin is also transcribed at lower levels
      in thymus, bone marrow, fetal liver and other fetal tissues, and in all
      proliferating cell lines tested. Thus haspin is likely to be important in
      regulation of diploid as well as haploid cell differentiation in a variety of
      tissues.

PMID- 11311557
TI  - The NIEHS Xenopus maternal EST project: interim analysis of the first 13,879 ESTs
      from unfertilized eggs.
AB  - The sequencing of expressed sequence tags (ESTs) from Xenopus laevis has lagged
      behind efforts on many other common experimental organisms and man, partly
      because of the pseudotetraploid nature of the Xenopus genome. Nonetheless, large
      collections of Xenopus ESTs would be useful in gene discovery, oligonucleotide
      based knockout studies, gene chip analyses of normal and perturbed development,
      mapping studies in the related diploid frog X. tropicalis, and for other reasons.
      We have created a normalized library of cDNAs from unfertilized Xenopus eggs.
      These cells contain all of the information necessary for the first several cell
      divisions in the early embryo, as well as much of the information needed for
      embryonic pattern formation and cell fate determination. To date, we have
      successfully sequenced 13,879 ESTs out of 16,607 attempts (83.6% success rate),
      with an average sequence read length of 508 bp. Using a fragment assembly
      program, these ESTs were assembled into 8,985 'contigs' comprised of up to 11
      ESTs each. When these contigs were used to search publicly available databases,
      46.2% bore no relationship to protein or DNA sequences in the database at the
      significance level of 1e-6. Examination of a sample of 100 of the assembled
      contigs revealed that most ( approximately 87%) were comprised of two apparent
      allelic variants. Expression profiles of 16 of the most prominent contigs showed
      that 12 exhibited some degree of zygotic expression. These findings have
      implications for sequence-specific applications for Xenopus ESTs, particularly
      the use of allele-specific oligonucleotides for knockout studies, differential
      hybridization techniques such as gene chip analysis, and the establishment of
      accurate nomenclature and databases for this species.

PMID- 11311558
TI  - Identification of alternative splicing of spinocerebellar ataxia type 2 gene.
AB  - Spinocerebellar ataxia 2 (SCA-2) is a neurodegenerative disorder caused by the
      expansion of an unstable CAG/polyglutamine repeat located at the NH(2)-terminus
      of ataxin-2 protein. Ataxin-2 is composed by 1312 aminoacids and it is expressed
      ubiquitously in human tissues. To date, the function of ataxin-2 is not known. In
      this study, we report the characterization of an alternative splice variant of
      human ataxin-2. The splice transcript lacks the exon 21 and connects exon 20 to
      exon 22 with the same reading frame of the full length mRNA. This novel isoform
      of ataxin-2 is conserved in the mouse. It is named type IV to differentiate it
      from type II splice variant lacking exon 10 (present in human and mouse cDNAs)
      and from type III, lacking exon 10 and exon 11 seen in mouse. Type IV of human
      ataxin-2 cDNA is predicted to encode a protein of 1294 residues. Both the full
      length and the type IV transcript of ataxin-2 are present in several human
      tissues, including brain, spinal cord, cerebellum, heart and placenta. These
      findings allow the hypothesis that type I, II and IV of human ataxin-2 might
      perform different functions.

PMID- 11311559
TI  - Identification, tissue expression, and chromosomal position of a novel gene
      encoding human ubiquitin-conjugating enzyme E2-230k.
AB  - Through large-scale human genome mapping and sequencing of a region at chromosome
      17q25.1 that is of particular interest because genes associated with breast,
      ovarian, and esophageal cancer are likely to be located there, we isolated the
      cDNA of a novel member of the family of ubiquitin-conjugating enzymes. The
      predicated peptide showed 97% identity in amino-acid sequence to murine ubiquitin
      conjugating enzyme E2-230k (Mus UBE2-230k). The human cDNA consisted of 4878
      nucleotides with an open reading frame encoding 1138 amino acids; the
      approximately 5 kb transcript was expressed predominantly in skeletal muscle and
      heart. The predicted UBE2-230k peptide contained a motif typical of the UBC
      domain that has been implicated in the ubiquitin-dependent proteolytic system and
      related pathways.

PMID- 11311560
TI  - Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ-domain
      Protein AIE-75.
AB  - AIE-75 is a protein identified as an autoantigen in patients with autoimmune
      enteropathy and as a colon cancer-related antigen. It has recently been assigned
      to be a causative gene for Usher type 1C congenital syndromic hearing loss. The
      novel protein has three PSD-95/Dlg/ZO-1 (PDZ) protein-protein interaction domains
      and is therefore implicated to function as a molecular anchor or sorter. We have
      identified a novel protein that binds to AIE-75 by yeast two-hybrid screening.
      The protein has a high homology to the tumor suppressor MCC (mutated in colon
      cancer; or MCC1 hereafter) and was named MCC2. MCC2 protein binds the first PDZ
      domain of AIE-75 with its C-terminal amino acids -DTFL. Since the MCC1 does not
      bind to AIE-75 and the MCC2 displays different expression patterns in various
      organs compared to MCC1, they appear to play distinct roles in cells. The MCC2
      gene is located on chromosome 19p13 in the vicinity of APCL gene, while MCC1 maps
      near to APC tumor suppressor gene. Because of negative expression of MCC2 in a
      panel of cancer cell-lines compared to the corresponding normal tissues, we
      suggest that further study is necessary to investigate a possible role of MCC2 as
      a tumor suppressor.

PMID- 11311561
TI  - Mammalian subunit IV isoforms of cytochrome c oxidase.
AB  - Cytochrome c oxidase (COX) contains ten nuclear encoded subunits, three of them
      known to show tissue isoforms in mammals. We have now found a fourth isoform, for
      subunit IV, in human, rat and mouse (COX IV-2). Comparison of the two human
      isoform genes shows a similar structural organization, including an overall size
      of about 8 kb, the presence of five exons, and the initiation of translation in
      the second exon, consistent with formation by gene duplication. Also consistent
      is the higher identity of precursor peptides of 78% within the new IV-2 isoform
      (average in the three species) compared to 44% average identity with the IV-1
      isoform. Northern analysis and quantitative PCR with human and rat tissues show
      high IV-2 expression in adult lung and lower expression in all other tissues
      investigated, including fetal lung. In contrast, the IV-1 isoform is ubiquitously
      expressed. In situ hybridizations were performed to localize isoform transcripts
      in rat lung. Both isoforms are found in similar ratios in most lung cell types
      except for smooth muscle and respiratory epithelium, which have a IV-2 and a IV-1
      preference, respectively. Structural modeling of the IV-2 isoform from human,
      based on the bovine crystal data, produces a conformation in which two of three
      conserved cysteine groups, exclusively present in the mammalian IV-2 isoform, are
      in close proximity. The formation of a cysteine bond and the implications for
      function of these sequence differences for subunit IV, which plays a pivotal role
      in COX regulation, are discussed.

PMID- 11311562
TI  - Identification and characterization of a human mitochondrial homologue of the
      bacterial co-chaperone GrpE.
AB  - We have identified a novel human cDNA with a predicted protein sequence that has
      28% amino acid identity with the E. coli Hsp70 co-chaperone GrpE and designated
      it HMGE. Even with this low level of amino acid identity the human sequence could
      be efficiently modelled on the X-ray structure of the E. coli protein, suggesting
      that there may be significant functional conservation. Indeed, HMGE expressed in
      E. coli as a GST fusion protein co-purified with the E. coli Hsp70 protein DnaK
      in the absence of ATP. DnaK could be released from the GST-HMGE with a Mg-ATP
      wash. Subcellular fractionation and immunocytochemistry studies using antisera
      raized against HMGE show that it is a mitochondrial protein. In contrast to
      studies of rat GrpE, however, HMGE also appears to bind the constitutive
      cytosolic Hsp70, Hsc70, in addition to mitochondrial Hsp70, Mt-Hsp70. We have
      previously shown that Hsc70 nucleotide-exchange is rate limiting in the presence
      of the DnaJ-protein, HSJ1b. However, HMGE was found to inhibit the HSJ1b-enhanced
      Hsc70 ATPase activity and may mediate this inhibition by binding the DnaJ
      protein, HSJ1b. This is the first description of a direct interaction between a
      DnaJ protein and GrpE-like protein. These studies suggest that the structure of
      GrpE has been conserved throughout evolution and that the conserved structure can
      interact with several forms of Hsp70, but that HMGE cannot form part of the
      reaction cycle for cytosolic Hsc70.

PMID- 11311563
TI  - Okadaic acid induces transcription of junB through a CCAAT box and NF-Y.
AB  - The shellfish toxin, okadaic acid (OA), is a potent tumor promoter that induces
      expression of the proto-oncogene junB in mouse keratinocyte 308 cells. Here we
      show, through deletion analysis of the junB promoter, that sequences near the
      TATA box conferred transcriptional induction by OA. Transient transfections of
      luciferase constructs bearing the junB promoter with single mutations in various
      cis elements demonstrated that a promoter containing a mutated CCAAT box could
      not be induced by OA. When this CCAAT box was inserted into a heterologous
      promoter construct, OA induction was dependent on an intact CCAAT box. Flanking
      cis elements located near the CCAAT box, although not required for OA
      inducibility, did play a role in the basal level of transcription. NF-Y was shown
      by EMSA to bind to the CCAAT box. OA induction from the junB CCAAT box was
      blocked by dominant negative NF-YA as well as the CCAAT box-dependent anticancer
      drug, ET-473. Expression of a lexA/NF-YA chimeric protein demonstrated that OA
      induction was dependent on the binding of NF-Y family members. These studies
      demonstrate that OA can mediate transcriptional activation of junB through the
      classical CCAAT box and that transcription factor NF-Y plays a functional role in
      the induction.

PMID- 11311564
TI  - Intrauterine versus postnatal transport of the preterm infant: a short-distance
      experience.
AB  - AIM: The purpose of this study was to compare neonatal outcome (mortality,
      respiratory distress syndrome, intraventricular hemorrhage, necrotising
      enterocolitis, persisting ductus arteriosus, and septicaemia) after intrauterine
      transport versus neonatal transport in an area where short-distance transport is
      the rule. METHODS: The study was retrospective in nature. The files of all
      neonates delivered between 24 and 34 weeks from 1994 to 1998 and transported
      intrauterine or postnatally to the Antwerp University Hospital were reviewed.
      Cases of intrauterine fetal death and mothers discharged before delivery were
      excluded, as were infants with lethal congenital anomalies. RESULTS: A total of
      328 deliveries after intrauterine transport, resulting in 416 neonates and 187
      neonates transported postnatally were included. The maximum distance patients had
      to be transported was 40 km. Placental abruption was more frequent in the mothers
      of the neonatal transport group (13 vs. 5%, P=0.001). Corticosteroids were
      administered significantly less in the neonatal transport group (67 vs. 13%,
      P<0.0001). Preterm rupture of the membranes (36 vs. 20%, P<0.0001), preterm
      labour (73 vs. 36%, P<0.0001), and pre-eclampsia (10 vs. 7%, P<0.0001) were more
      frequent in the intrauterine transport group and this group had a lower mean
      birthweight and gestational age. There was no significant difference for overall
      neonatal mortality, respiratory distress syndrome, intraventricular hemorrhage,
      necrotising enterocolitis, persisting ductus arteriosus or septicaemia.

PMID- 11311565
TI  - Endothelin-1 plasma concentration increases in the early phase of pulmonary
      hypertension development during respiratory distress syndrome: a study in newborn
      lambs.
AB  - OBJECTIVE: Elevated plasma concentrations of endothelin-1 (ET-1) have been
      reported with pulmonary hypertension during respiratory distress syndrome (RDS).
      However, the exact role of ET-1 in the development of pulmonary hypertension
      during RDS is unclear. The relative time-course of changes in ET-1 concentrations
      and pulmonary artery pressure (P(ap)) during RDS may give insight in the role of
      ET-1. METHODS: ET-1 and P(ap) changes were studied in an experimental model of
      RDS, induced by lung lavages in seven newborn lambs. Five other lambs served as
      controls. RESULTS: Lung lavages induced a twofold increase of mean P(ap) (from 15
      to 34 mm Hg) that remained present throughout the 4-h study period. Along with
      the increased P(ap), ET-1 plasma concentration showed a significant increase 15
      min after induction of RDS at all three sample locations (pulmonary artery 198%,
      aorta 181% and right atrium 195% compared to baseline). This increased
      concentration remained high at 1 and 4 h of RDS. In control animals, no
      significant changes in ET-1 concentrations were observed. Plotting ET-1
      concentration values against mean P(ap), in RDS and control animals at all time
      points, a correlation was found between the severity of the pulmonary
      hypertension and ET-1 concentration. CONCLUSION: This experimental model of RDS
      shows that ET-1 concentration increases concomitant with the development of
      pulmonary hypertension, from an early time point onward. More severe pulmonary
      hypertension is associated with higher ET-1 concentrations, but whether ET-1 is a
      marker or a mediator of pulmonary hypertension remains as yet unsettled.

PMID- 11311566
TI  - Sleep medicine in infants--practicability and limitations.
AB  - An increasing amount of polysomnographic studies are performed in early infancy.
      Complete pediatric sleep laboratory systems are commercially available and
      provide fast and exhaustive results if operated by trained personnel. Experience
      in evaluation is necessary, because a broad range of possible diagnostic findings
      exists, and artifacts are common. Based on longitudinal studies in 31 healthy
      infants, we present reference values for several polysomnographic parameters.
      Aberrant results must be interpreted in the context of patient's history,
      clinical state, and additional laboratory findings. In presence of a clearly
      defined indication for polysomnographic testing, clear therapeutic and
      interventional strategies can be derived. Possible consequences include the
      stimulation of the respiratory drive by drugs with subsequent polysomnographic
      control of therapeutic effect, a transfusion, the prescription of a home monitor,
      and the recommendation of further diagnostics or of control polysomnographies. In
      conclusion, infant polysomnography is an important diagnostic tool in pediatrics.

PMID- 11311567
TI  - Non-nutritive sucking in sick preterm infants.
AB  - BACKGROUND: Non-nutritive sucking (NNS) by the newborn infant is a fundamental
      behaviour and is one of the first coordinated muscular activities in the fetus.
      AIMS: Our objective is to study the NNS pattern in prematurely born infants, who
      had various conditions commonly associated with immaturity. METHOD: A specially
      designed computer-based method that analyses and quantifies components of the NNS
      pattern was used. SUBJECTS: The pattern of 51 clinically stable prematurely born
      infants (gestational ages 26-35 weeks) making a total of 206 observations were
      analysed and findings were compared with those obtained from 58, healthy preterm
      infants. RESULTS: The rhythmic NNS pattern of alternating sucking and pauses was
      elicited in all examined infants, the earliest at post-menstrual age (PMA) 26
      weeks. The role of PMA, the dominant predictor for several sucking variables seen
      in the control group, became diminished for the infants with risk factors but
      changes were otherwise similar. The infants' sucking activity and sucking
      frequency increased and the variability of the pattern declined with increased
      PMA and weight. Follow-up of a subgroup of infants revealed fewer sucking bursts
      per minute, slower sucking frequency and a greater variability of the frequency
      and amplitudes in those infants who developed sequelae. CONCLUSIONS: It would,
      thus, appear that the NNS pre-programmed rhythm generator, primarily modulated by
      maturation in healthy preterm infants, becomes affected by known risk associated
      events and in infants who later develop sequelae. Quantification of the NNS
      pattern in preterm infants may be a valuable future component of their
      evaluation.

PMID- 11311569
TI  - Iron-induced changes in nitric oxide and superoxide radical generation in rat
      liver after lindane or thyroid hormone treatment.
AB  - The involvement of cytosolic nitric oxide (NO) and mitochondrial superoxide
      radical (O2(.-)) production was evaluated as a mechanism triggering liver
      oxidative stress in lindane (40 mg/kg) or L-3,3',5-triiodothyronine (T3, 0.1
      mg/kg for 2 consecutive days) treated animals (male Sprague-Dawley rats)
      subjected to iron overload (200 mg/kg). Lindane and iron led to 504 and 210%
      increases in the content of hepatic protein carbonyls as an index of oxidative
      stress, with a 706% enhancement being produced by their combined administration.
      T3 did not alter this parameter, whereas iron overload increased the content of
      protein carbonyls by 116% in hyperthyroid rats. Lindane increased NO generation
      by 106% without changes in generation of O2(.-), whereas iron enhanced both
      parameters by 109 and 80% over control values, respectively, with a net 33 and
      46% decrease, respectively, being elicited by the combined treatment related to
      iron overload alone. Hyperthyroidism increased liver NO (69%) and O2(.-) (110%)
      generation compared to controls, effects that were either synergistically
      augmented or suppressed by iron overload, respectively. The in vitro addition of
      iron (1 micromol/mg protein) to liver cytosolic fractions from euthyroid (97%)
      and hyperthyroid (173%) rats also enhanced NO generation. The effects of iron
      overload on mitochondrial O2(.-) production by hyperthyroid rats were reproduced
      by the in vitro addition of 1 micromol iron/mg protein and abolished by the in
      vivo pretreatment with the iron chelator desferrioxamine (500 mg/kg). It is
      concluded that liver oxidative stress induced by iron overload is independent of
      NO and O2(.-) production in lindane-treated rats, whereas in hyperthyroid animals
      NO generation is a major factor contributing to this redox imbalance.

PMID- 11311570
TI  - Establishment of a chick embryo shell-less culture system and its use to observe
      change in behavior caused by nicotine and substances from cigarette smoke.
AB  - Early detection and removal of harmful factors are essential to the proper
      physical and psychological development of the fetus, presumably showing the
      effects during the prenatal period and after birth. As one procedure to aid in
      understanding such factors, we have established a shell-less culture system for
      video monitoring to observe change in behavior of 7-day-old chick embryos.
      Nicotine and aqueous cigarette smoke extract (ACSE) were selected for the present
      experiments, and the results showed a complete stoppage of swing-like movements
      by administrations of 10 microg nicotine and 1xACSE, possibly displaying
      paralytic symptoms. Quantitative analysis of nicotine in 1xACSE indicated that
      more than 10 microg of nicotine were contained in 100 microl of the extract. The
      present system, although in initial stage of development, may be a useful
      preliminary screening procedure for perhaps supervision and warning about the
      environment surrounding pregnant women.

PMID- 11311572
TI  - Phenobarbitone-induced ploidy changes in liver occur independently of p53.
AB  - Liver polyploidisation, characterised by accumulation of tetraploid and octaploid
      cells, is found with increasing age and after administration of various drugs.
      The significance and mechanisms controlling polyploidisation are not understood
      but p53 is a candidate gene to be involved. We have investigated the effect of
      p53 on sodium phenobarbitone (PB)-induced liver proliferation and
      polyploidisation. Using p53 wild type (+/+), heterozygous (+/-) and homozygous (
      /-) C57BL/6J mice, we measured ploidy and proliferation (BrdU incorporation)
      after 21 days oral administration of PB. Administration of PB caused a striking
      ploidy change compared with untreated controls, with an increase in 8n cells, and
      no difference noted comparing the p53 genotypes. BrdU positivity also increased
      significantly compared with controls, with the increase in BrdU positivity
      occurring in 8n cells. Our results confirm that PB is a hepatic mitogen that
      causes liver polyploidisation with a striking increase in 8n cells within the
      liver. p53 status does not appear to have any effect on this PB-induced ploidy
      change.

PMID- 11311571
TI  - Nitric oxide induces metallothionein (MT) gene expression apparently by
      displacing zinc bound to MT.
AB  - The metal binding protein metallothionein (MT) is involved in zinc homeostasis
      since it typically binds large amounts of zinc. Free zinc can control MT gene
      expression by interacting with metal-sensitive transcription factors. However,
      the precise factors governing intracellular release of metal ions from MT remain
      unknown. Aerobic nitric oxide (NO) can nitrosate thiol groups in proteins, and MT
      bound cadmium is released by NO exposure. Thus, we hypothesized that NO may also
      be effective at displacing zinc from MT in cultured cells and that this could be
      an important physiological control mechanism in zinc homeostasis and utilization.
      In this study, DETA/NO, an agent that spontaneously generates NO with a 20-h half
      life in physiological media, was used to study the release of zinc from MT and
      the induction of MT in TRL1215 cells (a normal rat liver cell line). Zinc or
      cadmium was given at levels inducing MT production, followed by DETA/NO (20-200
      microM) to produce controlled NO exposure in both cell lines. Although both
      metals activated MT gene expression, MT-I mRNA and MT protein were further
      increased when DETA/NO was given after zinc or cadmium treatment. Additionally,
      NO from DETA/NO clearly displaced MT-bound zinc, as evidenced by G-75 gel
      filtration chromatography. The released zinc or cadmium probably then stimulates
      further MT gene expression. These results suggest that NO may play an important
      role in regulation of cellular zinc homeostasis by providing a controlled release
      mechanism for metal ions stored in MT, and NO-mediated release of MT-bound zinc
      could in turn activate gene expression, such as with the MT gene.

PMID- 11311573
TI  - Diagnosis of cyanide intoxication by measurement of cytochrome c oxidase
      activity.
AB  - Cytochrome c oxidase (CCO), a mitochondrial enzyme, is inactivated by cyanide or
      carbon monoxide (CO) intoxication. We measured CCO activity, in the major organs
      of the rat at various times after death caused by cyanide intoxication. Tissue
      samples were homogenized, and the CCO activity in the mitochondrial fraction was
      measured using ferrous cytochrome c as the substrate. The CCO activity inhibition
      was highest in the brain, although the cyanide concentration was lowest level. As
      a result of this and the clinical symptoms displayed, we consider the brain to be
      the primary organ of cyanide intoxication. As cyanide is highly toxic to humans,
      in small amounts and many patients and victims have already had some medical
      care, it is difficult to detect cyanide in criminal investigations. The CCO
      activities in various organs remained significantly low for 2 days after the
      cyanide intoxication, suggesting that the diagnosis may be possible by measuring
      not only the cyanide concentration but also the CCO activity.

PMID- 11311574
TI  - Cytokine-mediated suppression of cytochrome P450 1A1 in Hepa-1c1c7 cells by
      pokeweed mitogen.
AB  - This study investigated the effects of pokeweed mitogen (PWM) on the regulation
      of cytochrome P450 (P450) 1A1 expression in an in vitro model, using murine
      hepatoma cell line Hepa-1c1c7 and murine macrophage cell line RAW 264.7 cell
      cultures. PWM added directly to Hepa-1c1c7 cells had no effect on 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced P450 1A1-specific 7-ethoxyresorufin O
      deethylase (EROD) activity. However, TCDD-induced EROD activity and P450 1A1 mRNA
      levels were markedly suppressed when Hepa-1c1c7 cells were cultured with PWM
      treated conditioned media from RAW 264.7 in a dose-dependent manner. Concomitant
      treatment with PWM and pentoxifylline, a TNFalpha synthesis inhibitor, to RAW
      264.7 cells decreased the suppressive effects of PWM on TCDD-induced EROD
      activity. In PWM-exposed RAW 264.7 cell cultures, TNFalpha and IL-6 levels
      increased in a dose-dependent fashion. When antibodies to TNFalpha or/and IL-6
      were added to PWM-treated conditioned media from RAW 264.7, the suppression of
      EROD activity was inhibited. These results suggested the suppression of P450 1A1
      by PWM was mediated exclusively by TNFalpha and IL-6, released from macrophages.

PMID- 11311575
TI  - Percutaneous permeation and skin irritation of JP-8+100 jet fuel in a porcine
      model.
AB  - JP-8 is the major jet fuel used by US Air Force. JP-8+100 is a new jet fuel
      recently introduced by the US Air Force, which contains JP-8 plus three
      performance additives [butylated hydroxytoluene (BHT), metal deactivator (MDA)
      and 8Q405]. The purpose of the present study was to investigate the percutaneous
      permeation of JP-8+100 across pig ear skin in vitro and to study the effect of JP
      8+100 exposure on the skin barrier function, moisture content and irritation in
      Yucatan minipigs. The influence of performance additives on the permeation of JP
      8 was studied by adding each additive individually to JP-8. The percutaneous
      permeation and skin irritation data obtained with JP-8+100 were compared with
      that of JP-8. JP-8+100 spiked with 5.0 microCi of radiolabeled [14C]tridecane,
      nonane, naphthalene or toluene (selected components of JP-8+100) was used for the
      in vitro percutaneous permeation studies. For skin irritation studies, 250 microl
      of JP-8+100 was placed in a Hill top chamber and affixed over the marked
      treatment area for 24 h. The components of JP-8+100 such as tridecane, nonane,
      naphthalene and toluene permeated readily through pig ear skin without any
      apparent lag time. Compared to JP-8, the permeation of tridecane, toluene and
      nonane from JP-8+100 was significantly lower (P<0.05). However, the permeation of
      naphthalene from JP-8+100 was significantly higher than from JP-8. When BHT was
      added to JP-8, the permeation of all four chemicals were significantly decreased
      (P<0.05). Though the addition of 8Q405 to JP-8 decreased the permeation of all
      four chemicals, the values were not significantly different (P>0.05) from that of
      JP-8. Addition of MDA did not show any significant change in the permeation of
      the selected chemicals from JP-8. Application of JP-8+100 increased the
      transepidermal water loss (TEWL) about three times compared to the baseline
      level. The skin moisture content decreased consistently after the application of
      JP-8+100, though it was not significantly different (P>0.05) from the baseline
      level. JP-8+100 caused a moderate erythema (score: 1.60) and a moderate to severe
      edema (score: 2.60). These results suggest that JP-8+100 produces significant
      changes in the barrier function of the skin and a local irritant effect upon
      occlusive dermal exposure. However there was no significant difference in the
      skin irritation data observed from JP-8 and JP-8+100.

PMID- 11311576
TI  - Carbofuran suppresses T-cell-mediated immune responses by the suppression of T
      cell responsiveness, the differential inhibition of cytokine production, and NO
      production in macrophages.
AB  - The effects of carbofuran (2,3-dihydro-2,2-dimethyl-7-benzo-furanol N
      methylcarbamate) on the functions of T cells in splenocytes and peritoneal
      macrophages were examined in view of T-cell-mediated immune response (CMIR) in
      male C57BL/6 mice. Intraperitoneal administration of carbofuran (0.075, 0.15 and
      0.3 mg/kg body weight) resulted in significant suppression of delayed type
      hypersensitivity (DTH), indicating that it caused the suppression of CMIR.
      Carbofuran decreased Concanavalin A (Con A)- and alloantigen-induced
      proliferation, and interleukin (IL)-2 production of splenocytes. In vitro
      addition of rIL-2 could not completely restore the suppressed T-cell
      proliferation, and IL-2-induced proliferation of Con A-activated splenocytes was
      also suppressed, which implied that carbofuran caused defects in IL-2 production
      and responsiveness of splenocytes to IL-2, leading to the suppression of T-cell
      proliferation. Con A-induced production of interferon-gamma (IFN-gamma) was
      significantly suppressed by carbofuran, while that of IL-4 was not affected. The
      production of transforming growth factor-beta from splenocytes was also
      significantly inhibited by carbofuran. Judging from these results, carbofuran
      might directly suppress the cytokine production in T helper 1 (Th1) cells. In
      addition, IFN-gamma-induced production of nitric oxide (NO) in macrophages was
      also inhibited by carbofuran, which might be one of the important mechanisms of
      carbofuran-induced CMIR suppression in mice. Collectively, the present study
      suggests that carbofuran might suppress CMIR through the suppression of T-cell
      responsiveness, IFN-gamma production in Th1 cells, and NO generation in
      macrophages.

PMID- 11311577
TI  - Improved risk assessment by screening sperm parameters.
AB  - The question of whether a 4 or 9 week premating treatment period is more suitable
      in studies for effects on fertility and early embryonic development, and the
      extent to which the screening of sperm parameters may contribute to the detection
      of effects, has been under discussion since the ICH guideline changed in
      1994/1995. This study presents a comparison between 4 and 9 weeks treatment with
      known male reproductive toxicants with regard to sperm motility, count,
      morphology, abnormal movements and testicular and epididymal histopathology.
      Mating outcome was examined after 4 weeks treatment. Three compounds with
      different targets and mechanisms of action were chosen: two testicular toxicants,
      Pyridoxine and Adriamycin and the epididymal toxicant, alpha-Chlorohydrine. Sperm
      motility was reduced in males treated with Pyridoxine (markedly) and alpha
      Chlorohydrine (slightly) after 4 weeks treatment and in males treated with
      Adriamycin after 9 weeks treatment. With Pyridoxine and Adriamycin, sperm count
      was significantly increased after 4 weeks. Histopathological examination after 4
      weeks showed characteristic changes leading to marked testicular tubular atrophy
      at 8/9 weeks, which was confirmed by a significantly reduced sperm count at 8/9
      weeks. With alpha-Chlorohydrine, sperm count was not affected and the results of
      the histopathological examination were equivocal. Changes in sperm morphology
      were observed after 4/9 weeks of treatment with Pyridoxine. Mating outcome after
      4 weeks was markedly affected with both Pyridoxine and alpha-Chlorohydrine, but
      no effect was observed with Adriamycin. The results of this study indicate that
      the two testicular toxicants would have been detected as male reproductive
      toxicants in a 4-week general toxicity study with routine testicular
      histopathology and examination of sperm parameters, without the need for mating
      trials. For the epididymal toxicant, alpha-Chlorohydrine, there was slightly
      reduced sperm motility after 4 weeks treatment, but mating trials were necessary
      for confirmation of the toxic effect. Without sperm motility examination, this
      effect would have been missed in early drug development causing problems in
      clinical studies. Further comparisons of the validity of 4 or 9 weeks treatment
      require the testing of other compounds with different targets/mechanism of
      actions, as well as evaluation of dose-response relationships.

PMID- 11311578
TI  - Hormones and Ageing. Proceedings of a symposium. The Netherlands, December 1999.

PMID- 11311579
TI  - The demographic revolution and our common future.
AB  - The global population reached two billion people in 1927 and six billion in 1999.
      If the medium variant projection of the United Nations were to materialize, the
      Earth's population would reach nine billion in 2054. However, such a brave new
      world will be inhabited by a brave old humankind; in 2050, 16.4% of the world
      population and 27.6% of the European population are projected to be 65 years and
      above, and in 14 countries, including nine European ones, more than 10% of the
      total population will be 80 years or older. The United Nations also project a
      world-wide decline in the number of children and in total fertility, and by 2050,
      there will be more elderly than children in several parts of the world,
      particularly in Europe. It seems likely that many of our classical institutions,
      for instance healthcare -- unless reformed -- will cater increasingly for the
      needs of a population structure that no longer exists. The World Health
      Organization projects that by the year 2020, global health trends will be
      dominated by the ageing of the world population, the HIV/AIDS epidemic, tobacco
      related mortality and declining child mortality. Furthermore, the leading causes
      of disease burden will be heart disease, depression and traffic accidents. How
      can we meet the giant challenges of the 21st century? In the view of the author,
      the most rational remedy must be a quantum leap in research in general and in
      medical research in particular.

PMID- 11311581
TI  - DNA repair mechanisms.

PMID- 11311583
TI  - Telomeres, replicative senescence and human ageing.
AB  - Ageing concerns the extracellular environment and cells that are either post
      mitotic or capable of division during life. Primary human cells have a finite
      division capacity in culture before they enter a state of viable cell cycle
      arrest termed senescence. Cell division occurs during life in many tissues,
      either as part of normal tissue function or in response to tissue damage. The
      accumulation of cells at the end of their replicative lifespan in the elderly
      might contribute to aged tissue either because of a reduced ability to undergo
      proliferation or because of the known altered gene-expression patterns of
      senescent cells. This has been illustrated experimentally using a transgenic
      telomerase-negative mouse, which shows some premature ageing phenotypes. The
      mechanism whereby cells count divisions uses the gradual erosion of the ends of
      chromosomes (telomeres) with cell division caused by the repression of the
      telomere-maintenance enzyme telomerase in most human cells. Telomere erosion
      ultimately triggers replicative senescence in many cell types; this can be
      prevented experimentally by forcibly expressing telomerase. This extends the
      lifespan of normal human cells and those from progeroid syndromes such as
      Werner's. Telomere-driven senescence did not evolve to cause ageing, but is
      instead a by-product of a system devised to provide a tumour-suppression
      function, a concept that fits well with evolutionary arguments regarding trade
      offs between somatic maintenance and reproduction. Work in the future will focus
      on the development of new animal models to critically address the quantitative
      significance of this ageing mechanism.

PMID- 11311585
TI  - Apoptosis and aging: breast cells and apoptosis.

PMID- 11311587
TI  - Vascular effects of hormones.

PMID- 11311589
TI  - Depression in the elderly: findings from a community survey.

PMID- 11311591
TI  - Androgens and aging.
AB  - This review supports the conclusion that the use of testosterone replacement
      therapy for the treatment of the symptoms of androgen deficiency in aging males
      (ADAM) may be appropriate if undertaken with due caution. The best safety data
      exists for using oral therapy with testosterone undeconoate. Less data exists for
      the treatment of postmenopausal women with testosterone. Tibolone (an estrogen-
      prostagen--testosterone) compound, may make the need for testosterone being added
      to estrogen in women unnecessary. Less data is available to support the use of
      DHEA or its sulfate or pregnenolone. Further studies are clearly necessary in all
      these areas. However, it may be tentatively concluded that we are at the dawning
      of the age of androgens.

PMID- 11311593
TI  - Meeting nutrient and energy requirements in old age.
AB  - In old age, the complex relation of food consumption with energy and nutrient
      requirements finds expression in both single and multiple nutritional problems.
      Addressing conditions affecting intake -- either from foods or from supplements -
      endogenous production, bioefficacy and/or requirements can benefit nutritional
      health in old age through balancing requirements and supply.

PMID- 11311595
TI  - Hormones and reproductive aging.

PMID- 11311597
TI  - Estrogen and the aging brain.
AB  - Evidence is presented indicating a role for estrogen in the function and
      maintenance of the aging brain. Based on complementary data that estrogen
      regulates the function of the immune--brain barrier, the hypothesis is presented
      that estrogen contributes to brain homeostasis via regulation of microglial
      activation, enabling immune-privileged status in the brain. Diminished estrogen
      levels during the menopause compromise the immune--brain barrier fostering
      inflammatory processes in the brain. This has potentially lethal consequences for
      brain cells, and may contribute to brain pathologies such as Alzheimer's disease.

PMID- 11311599
TI  - Breast cancer: hormones and other risk factors.
AB  - In North America and Northern Europe, breast cancer incidence rates begin
      increasing in the early reproductive years and continue climbing into the late
      seventies, whereas rates plateau after menopause in japan and less developed
      countries. Female gender, age and country of birth are the strongest determinants
      of disease risk. Family history and mutations in the BRCA1 and BRCA2 genes are
      important correlates of lifetime risk. Genetic polymorphisms associated with
      estrogen synthesis and metabolism are currently under study. Atypical hyperplasia
      and molecular alterations in benign breast lesions appear to be involved in the
      pathogenesis of invasive carcinoma. In postmenopausal women, increased breast
      density on mammograms increases risk. Bone density and breast cancer are
      associated, presumably through the mechanism of endogenous estrogen levels. Serum
      estrogen levels are higher in breast cancer cases than controls. Many established
      risk factors for breast cancer may function through and endocrine mechanism.
      Current use of oral contraceptives and prolonged, current or recent use of
      hormone replacement therapy moderately increase risk. Tamoxifen and possibly
      other selective estrogen receptor modulators reduce breast cancer risk in high
      risk women. Relationships between various dietary micro and macronutrients and
      breast cancer have been suggested but require evaluation in clinical trials.
      Whereas alcohol consumption is associated with increased risk, most environmental
      factors, including polychlorinated compounds and electromagnetic fields, are not.
      CONCLUSION: Breast cancer etiology is becoming clearer through the study of
      molecular alterations in germline and somatic cell genes, and the interaction of
      these genes with steroid hormones and relevant growth factors. This knowledge
      should be useful for breast cancer prevention.

PMID- 11311601
TI  - General discussion.

PMID- 11311602
TI  - The squared, sharp-edged optic intraocular lens design.

PMID- 11311603
TI  - Consultation section: Cataract surgical problem.

PMID- 11311614
TI  - Deep sclerectomy with a collagen implant using the excimer laser.
AB  - We describe a new technique of nonpenetrating glaucoma surgery that uses the
      excimer laser to reduce the risk of perforating the trabeculo-Descemet's
      membrane. With this technique, the ablation is precise and homogeneous. A
      collagen device is sutured over the scleral bed to create an outflow pathway for
      aqueous humor drainage. After a superficial scleral flap is dissected with a
      diamond knife, the sclera, under direct visualization, is ablated with the
      excimer laser over Schlemm's canal until aqueous humor percolates through from
      the anterior chamber. A collagen device is placed over the sclera to allow the
      aqueous humor to flow from the anterior chamber through the trabeculo-Descemet's
      membrane. The preliminary results show a drop in intraocular pressure to the
      middle teens.

PMID- 11311615
TI  - Ultrasound biomicroscopy and intraocular-pressure-lowering mechanisms of deep
      sclerectomy with reticulated hyaluronic acid implant.
AB  - PURPOSE: To evaluate the anatomic characteristics and intraocular pressure (IOP)
      lowering mechanisms of deep sclerectomy with reticulated hyaluronic acid implant
      (DS with RHAI) using ultrasound biomicroscopy (UBM). SETTING: Eye Clinic,
      Department of Neurological and Vision Sciences, University of Verona, Verona,
      Italy. METHODS: Thirty patients with primary open-angle glaucoma not controlled
      by medical therapy had DS with RHAI in 1 eye. A complete ocular examination and
      UBM study were performed 1, 3, 6, and 12 months postoperatively and thereafter at
      6 month intervals. Eleven parameters were evaluated, the most important of which
      were IOP, surgical success in lowering IOP to 21 mm Hg or less with or without
      additional medical therapy, UBM appearance of the site of DS with RHAI, size of
      the decompression space, presence of a filtering bleb and supraciliary hypoechoic
      area, and scleral reflectivity around the decompression space. RESULTS: After a
      mean follow-up of 11.4 months +/- 4.7 (SD), the mean percentage reduction in IOP
      compared to preoperatively was 38% (from 26 +/- 4.5 mm Hg to 16.2 +/- 3.8 mm Hg;
      P =.0001). Twenty-four patients (80%) had an IOP less than 21 mm Hg; however, 7
      of these eyes (23%) required additional IOP-lowering medical therapy. The
      operation failed in 6 patients (20%) despite additional therapy. Ultrasound
      biomicroscopy revealed a reduction in the size of the decompression space from 6
      months postoperatively and its disappearance in 2 cases. The difference in size
      at the last follow-up and at 1 month postoperatively (maximum length 2.41 +/-
      1.02 mm versus 3.53 +/- 0.51 mm) was significant (P =.0001). At the last
      examination, a filtering bleb was present in 18 patients (60%), a supraciliary
      hypoechoic area in 18 (60%), and hyporeflectivity of the scleral tissue around
      the decompression space in 14 (47%). These 3 UBM characteristics were detected
      singly and in various combinations. The simultaneous presence of all 3
      characteristics in the same eye correlated significantly with a higher surgical
      success rate (P =.004). CONCLUSIONS: Ultrasound biomicroscopy showed that
      filtering bleb formation was frequent in eyes having DS with RHAI but that it was
      not the only surgically induced IOP-lowering mechanism. Increased uveoscleral and
      transscleral filtration may be equally important.

PMID- 11311616
TI  - Short-term effect of mitomycin-C augmented trabeculectomy on axial length and
      corneal astigmatism.
AB  - PURPOSE: To evaluate the short-term effect of trabeculectomy with adjunctive
      mitomycin-C (MMC) on corneal astigmatism and axial length. SETTING: Asan Medical
      Center, University of Ulsan, Department of Ophthalmology, Seoul, Korea. METHODS:
      Eighteen consecutive eyes of 16 patients having trabeculectomy with adjunctive
      MMC were prospectively analyzed. Intraocular pressure (IOP) and axial length were
      evaluated preoperatively and 1, 3, 6, and 12 months postoperatively.
      Postoperative changes in corneal astigmatism were evaluated using vector
      analysis. RESULTS: The overall mean induced astigmatism showed with-the-rule
      change up to 3 months postoperatively followed by an against-the-rule shift. The
      mean axial length was significantly less postoperatively and changed throughout
      the 12 month follow-up. There was a positive correlation between postoperative
      axial length and IOP. Eyes with higher preoperative IOP had a greater decrease in
      axial length after trabeculectomy with MMC. CONCLUSION: The induced corneal
      astigmatism after trabeculectomy with MMC was long lasting, although less than
      that in previous studies. The change in axial length after surgery was
      significant, especially in eyes with a high preoperative IOP. The decrease in
      axial length persisted throughout the follow-up.

PMID- 11311617
TI  - Evaluation of intraocular pressure in the immediate period after
      phacoemulsification.
AB  - PURPOSE: To determine the incidence of hypotony or intraocular pressure (IOP)
      spikes in the early period after clear corneal phacoemulsification in normal and
      glaucomatous eyes. SETTING: Ambulatory surgical center. METHODS: This
      retrospective analysis comprised 112 eyes that had clear corneal
      phacoemulsification. Postoperative IOP measurements were collected 30 minutes, 1
      day, and 1 month after surgery. RESULTS: Twenty-three eyes had an IOP of 5 mm Hg
      or below 30 minutes postoperatively. The IOP at 30 minutes was lower than at 1
      day in both the normal and the glaucoma group. The mean IOP in the normal group
      was 10.0 mm Hg +/- 4.3 (SD) at 30 minutes and 16.9 +/- 4.4 mm Hg at 1 day (P < or
      = .005). The means in the glaucoma group were 9.6 +/- 3.9 mm Hg and 16.9 +/- 5.7
      mm Hg, respectively (P < or = .0002). The IOPs at 30 minutes and 1 day were not
      significantly different between the 2 groups. CONCLUSIONS: A significant
      percentage of eyes having clear corneal phacoemulsification had an IOP of 5 mm Hg
      or less 30 minutes after surgery. Even though there were no postoperative
      complications from hypotony and there was a relative absence of significant IOP
      elevation 1 day postoperatively, the frequency of low IOP at 30 minutes suggests
      that consideration be given to leaving postoperative eyes with a higher IOP at
      the completion of phacoemulsification rather than with the estimated 10 mm Hg
      tactile IOP strived for in this study.

PMID- 11311618
TI  - Intraocular pressure decrease after phacoemulsification in patients with
      pseudoexfoliation syndrome.
AB  - PURPOSE: To determine the intraocular pressure (IOP) response to
      phacoemulsification cataract extraction with posterior chamber intraocular lens
      (PC IOL) implantation in patients with pseudoexfoliation syndrome. SETTING: Eye
      clinics at the University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
      METHODS: A retrospective cohort study design assigned patients to 1 of 3
      subgroups: pseudoexfoliation syndrome (PEX) (n = 21), primary open-angle glaucoma
      (POAG) control (n = 23), and cataract control (n = 23). Inclusion criteria
      consisted of age older than 50 years, open angle by gonioscopy, and a cataract
      requiring phacoemulsification. The IOP response was determined at intervals up to
      18 months. RESULTS: Postoperative IOP changes from baseline in the PEX group were
      -1.81, -4.52, and -2.31 mm Hg at 3, 6, and 12 months, respectively. The changes
      in the POAG control group were -2.22, -2.32, and -1.88 mm Hg, respectively, and
      in the cataract control group, -2.49, +0.45, and +0.28 mm Hg. Patients in the PEX
      group had a reduction in IOP from baseline at all postoperative measurements.
      That reduction was significantly greater than in the POAG and cataract control
      groups at 6 months (P =.012 and P =.002, respectively) and 12 months (P =.001 and
      P =.050, respectively). CONCLUSIONS: Patients with pseudoexfoliation syndrome had
      a postoperative IOP reduction from baseline at all measurements and a
      significantly greater reduction than patients in the POAG and cataract control
      groups at 6 and 12 months. Phacoemulsification cataract surgery with PC IOL
      implantation may be effective in managing patients with pseudoexfoliation
      syndrome who have elevated IOP and visually significant cataract but no advanced
      optic nerve damage.

PMID- 11311619
TI  - Biometry of 3 types of intraocular lenses using Scheimpflug photography.
AB  - PURPOSE: To compare differences in intraocular lens (IOL) decentration and tilt
      and anterior chamber depth (ACD) using Scheimpflug photography as well as best
      corrected visual acuity (BCVA) in eyes having phacoemulsification with
      implantation of 1 of 3 types of IOLs. SETTING: Chung-Ang University Hospital,
      Seoul, Korea. METHODS: This study comprised 137 cataractous eyes of 108 patients
      having phacoemulsification and IOL implantation. Eyes were randomized into 3
      groups based on IOL type: poly(methyl methacrylate) (PMMA) (n = 65); silicone (n
      = 47); soft acrylic (n = 25). Biometric analysis was performed with an EAS-1000
      Scheimpflug camera 1, 3, and 6 months after surgery. Best corrected visual acuity
      was also measured at these visits. RESULTS: The anterior chamber was deeper 1
      month after surgery, with no statistical difference among groups. There were no
      significant differences among groups in IOL decentration and tilt or final BCVA
      during the follow-up. CONCLUSIONS: In this study in which a properly constructed
      continuous curvilinear capsulorhexis was created and IOLs were accurately placed
      in normal capsular bags, changes in ACD, IOL decentration and tilt, and BCVA were
      similar in eyes with a PMMA, silicone, or soft acrylic IOL.

PMID- 11311620
TI  - Change in the area of laser posterior capsulotomy: 3 month follow-up.
AB  - PURPOSE: To monitor the change in the area of laser posterior capsulotomy over
      time to determine whether and when the area becomes stable. SETTING: Taipei
      Municipal Yang-Ming Hospital, Taipei, Taiwan, Republic of China. METHODS: This
      prospective study comprised 53 eyes (46 patients) with posterior capsule
      opacification (PCO) that had neodymium:YAG (Nd:YAG) laser posterior capsulotomy.
      The capsulotomy area was measured 30 minutes, 1 week, and 1 and 3 months
      postoperatively. The correlations between the capsulotomy area and changes in
      other measurements were also evaluated. RESULTS: The capsulotomy area increased
      significantly 1 month after laser treatment and stabilized thereafter. The mean
      area increased from 9.26 mm(2) +/- 0.47 (SEM) to 10.88 +/- 0.66 mm(2) (17.49%)
      after 3 months. At 3 months, the area was 19.10% +/- 4.85% larger than at 30
      minutes after capsulotomy. The change in area did not correlate significantly
      with changes in intraocular pressure, anterior chamber depth, spherical
      equivalent, refractive astigmatism, keratometric astigmatism, or residual
      astigmatism from 1 week after treatment. CONCLUSION: The capsulotomies enlarged
      progressively up to 1 month after Nd:YAG laser posterior capsulotomy for PCO and
      stabilized thereafter.

PMID- 11311621
TI  - Intraocular lens power calculation for lens exchange.
AB  - PURPOSE: To examine patients who had intraocular lens (IOL) exchange for large
      postoperative refractive errors and determine the factors that contributed to the
      error in IOL power calculation. SETTING: Thirteen affiliated hospitals in Japan.
      METHODS: This study comprised 34 cases that required IOL exchange because of
      large refractive errors after primary lens implantation. Patients with
      intraoperative complications were excluded from the study. The potential
      contribution of axial length, corneal refractive power, IOL manufacturer, and IOL
      fixation to errors in the predicted power was examined retrospectively. Axial
      length was calculated by the SRK/T and Holladay formulas using refraction after
      primary IOL implantation. RESULTS: There was no statistical difference between
      the corneal refractive power before and after cataract surgery. The axial lengths
      calculated using the SRK/T and Holladay formulas were longer than the ultrasonic
      axial lengths in 24 and 23 cases, respectively. Using IOLs from the same
      manufacturer for both primary implantation and exchange reduced the error in
      predicted refraction. CONCLUSION: Axial length and IOL manufacturer were
      important factors in predicting refraction power in eyes requiring IOL exchange.

PMID- 11311622
TI  - Occult wound leak diagnosed by ultrasound biomicroscopy in patients with
      postoperative hypotony.
AB  - PURPOSE: To describe the ability of high-frequency ultrasound biomicroscopy (UBM)
      to diagnose occult wound leaks as a cause for hypotony after cataract surgery.
      METHODS: Six patients with persistent hypotony after cataract surgery were sent
      for UBM examination. Slitlamp examination and gonioscopy of the 6 eyes had not
      revealed a cause for the hypotony. RESULTS: Ultrasound biomicroscopy showed
      subtle wound separation with shallow conjunctival elevation at the site of the
      cataract wound in the 6 patients. Two eyes had surgical repair of the
      subconjunctival wound leak, and the other 4 were treated medically. In the 2 eyes
      with surgically repaired wounds, the hypotony cleared after wound closure. Of the
      4 medically treated eyes, hypotony resolved in 2 and 1 had a recurrence of
      hypotony. The other 2 eyes had fluctuating intraocular pressure for an extended
      period. CONCLUSIONS: Hypotony after cataract surgery occurred in 6 eyes due to
      subtle wound leaks difficult to detect by clinical observation. Ultrasound
      biomicroscopy can be a helpful aid to clinical examination in detecting these
      leaks.

PMID- 11311623
TI  - Early postoperative capsular block syndrome.
AB  - PURPOSE: To report the results of early postoperative capsular block syndrome
      (CBS) after phacoemulsification and intraocular lens (IOL) implantation. SETTING:
      Department of Ophthalmology, Dokuz Eylul University School of Medicine, Izmir,
      Turkey. METHODS: Thirteen eyes of 13 patients with CBS who had uneventful
      phacoemulsification were included in the study. Twelve patients had in-the-bag
      implantation of a foldable IOL, and 1 had implantation of a poly(methyl
      methacrylate) IOL in the ciliary sulcus. Continuous curvilinear capsulorhexis was
      performed in all eyes, and sodium hyaluronate 1.4% (Healon GV(R)) was used during
      all steps of surgery. The patients were closely followed without intervention
      during the first month after surgery. If resolution did not occur during follow
      up, a neodymium:YAG (Nd:YAG) laser peripheral anterior capsulotomy was performed
      first, followed by posterior capsulotomy if the anterior capsulotomy was not
      successful. RESULTS: The CBS resolved without intervention in 2 eyes by 1 month
      postoperatively. A small Nd:YAG laser peripheral anterior capsulotomy was
      attempted in 10 cases after 1 month but could not be performed in 2 eyes because
      of inadequate pupil dilation. Peripheral anterior capsulotomy was successful in 5
      of 8 eyes, with resolution of CBS in a few days. The Nd:YAG laser posterior
      capsulotomy was successful in 5 cases after the failure of the anterior
      capsulotomy. One patient chose to postpone treatment for 11 months, at which time
      posterior capsulotomy was performed successfully and the CBS resolved.
      CONCLUSIONS: Resolution of CBS occurred spontaneously in only a small percentage
      of cases during the first month after phacoemulsification with IOL implantation.
      Neodymium:YAG laser peripheral anterior capsulotomy and posterior capsulotomy
      were successful in treating CBS.

PMID- 11311624
TI  - Effect of brimonidine tartrate ophthalmic solution 0.2% on pupil size in normal
      eyes under different luminance conditions.
AB  - PURPOSE: To evaluate the effect of brimonidine tartrate ophthalmic solution 0.2%
      (Alphagan) on pupil size in normal eyes. Three luminance conditions were used to
      assess the potential use of brimonidine in postoperative refractive patients who
      experience nighttime vision problems related to large pupil size. SETTING:
      McDonald Eye Associates, Fayetteville, Arkansas, USA. METHODS: Pupil size was
      measured in 16 eyes of 16 participants with the Colvard pupillometer under 3
      luminance conditions. One drop of brimonidine 0.2% was administered to each
      patient. Pupil size was then measured using the same technique 30 minutes and 4
      and 6 hours after drop administration. RESULTS: Under scotopic conditions, 100%
      of the pupils showed significant miosis at 30 minutes (P <.05). The effect
      continued in all eyes for 4 hours. At 6 hours, a miotic effect was still present
      in 81.3%. However, under photopic luminance, there was no significant effect on
      pupil size in all 16 eyes (P >.05). The pupil size in 5 eyes (31.2%) was not
      affected at 30 minutes or 4 or 6 hours. At 6 hours, 15 eyes (93.8%) had returned
      to their preinstillation size. CONCLUSION: Brimonidine tartrate 0.2% had a
      significant effect in decreasing pupil size under scotopic conditions. The
      results indicate that the drug can decrease night-vision difficulties such as
      halos, star bursts, glare, and monocular diplopia in postoperative refractive
      patients.

PMID- 11311625
TI  - Comparison of laser epithelial keratomileusis and photorefractive keratectomy for
      low to moderate myopia.
AB  - PURPOSE: To compare the effectiveness, safety, and stability of laser epithelial
      keratomileusis (LASEK), a modified photorefractive keratectomy (PRK) technique,
      with those of conventional PRK for low to moderate myopia. SETTING: Department of
      Ophthalmology, Yonsei University School of Medicine, Seoul, Korea. METHODS: In
      this prospective study, 27 patients with a manifest refraction of -3.00 to -6.50
      diopters were treated and followed for 3 months. In each case, PRK was performed
      in 1 eye and LASEK in the other eye. The first eye treated and the surgical
      method used in the first eye were randomized. Postoperative pain, epithelial
      healing time, uncorrected visual acuity (UCVA), manifest refraction, corneal
      haze, and surgical preference were examined in PRK- and LASEK-treated eyes.
      RESULTS: During the 3 month follow-up, there were no significant between-eye
      differences in epithelial healing time, UCVA, or refractive error. However, LASEK
      treated eyes had lower postoperative pain scores (P =.047) and corneal haze
      scores (1 month; P =.02) than PRK-treated eyes. Seventeen patients (63%)
      preferred the LASEK procedure. CONCLUSIONS: Laser epithelial keratomileusis
      safely and effectively treated eyes with low to moderate myopia. It reduced the
      incidence of significant postoperative pain and corneal haze and may prevent the
      flap- and interface-related problems of laser in situ keratomileusis.

PMID- 11311626
TI  - Accuracy and predictability of intraocular lens power calculation after laser in
      situ keratomileusis.
AB  - PURPOSE: To study the accuracy and predictability of intraocular lens (IOL) power
      calculation in eyes that had laser in situ keratomileusis (LASIK). SETTING:
      Gimbel Eye Centre, Calgary, Alberta, Canada. METHODS: Refractive outcomes in 6
      cataract surgery and lensectomy eyes after previous LASIK were analyzed
      retrospectively. Target refractions based on measured and refraction-derived
      keratometric values were compared with postoperative achieved refractions.
      Differences between target refractions calculated using 5 IOL formulas and 2 A
      constants and achieved refractions were also compared. RESULTS: The refractive
      error of IOL power calculation in postoperative LASIK eyes was significantly
      reduced when refraction-derived keratometric values were used for IOL power
      calculation. Persistent residual hyperopia still occurred in some cases; this was
      corrected by hyperopic LASIK. Refractive results appeared more accurate and
      predictable when the Holladay 2 or Binkhorst 2 formula was used for IOL power
      calculation. CONCLUSION: Hyperopic error after cataract surgery in post-LASIK
      eyes was significantly reduced by using refraction-derived keratometric values
      for IOL power calculation. Persistent hyperopic error was corrected by hyperopic
      LASIK.

PMID- 11311627
TI  - Symptoms of dry eye and recurrent erosion syndrome after refractive surgery.
AB  - PURPOSE: To determine the incidence and severity of patient complaints typical of
      dry eye and recurrent erosion syndrome after excimer laser refractive surgery and
      to compare the incidence of these symptoms after photorefractive keratectomy
      (PRK) and laser in situ keratomileusis (LASIK). SETTING: Outpatient university
      practice. METHODS: A questionnaire was mailed to 1731 patients who had had
      primary myopic PRK or LASIK at least 6 months previously. Questions were designed
      to determine the incidence and character of ocular dryness and recurrent erosion
      symptoms and their impact on patient satisfaction and willingness to have surgery
      again. Responses from PRK and LASIK patients were compared. RESULTS: Responses
      from 231 PRK patients and 550 LASIK patients revealed an incidence of dryness
      symptoms in 43% and 48%, respectively (P >.05). Soreness of the eye to touch was
      reported by 26.8% and 6.7%, respectively (P <.0001). Sharp pains occurred in
      20.4% of PRK patients and 8.0% of LASIK patients (P =.0001). Complaints of the
      eyelid sticking to the eyeball occurred in 14.7% and 5.6%, respectively (P
      =.0001). All symptoms occurred predominantly on waking. Frequency of eyelid
      sticking (P <.0005) and sharp pain (P <.005) symptoms, as well as severity of
      sharp pain symptoms (P <.0001), were significantly greater in PRK patients than
      in LASIK patients. On a scale of 0 to 10 (10 high), median overall patient
      satisfaction with surgery was 9 in both groups. Soreness of the eyelid to touch
      occurred significantly more frequently among patients with symptoms of sharp
      pains on waking (P <.001) and the sensation of the eyelid sticking to the eyeball
      (P <.001). Patients with 1 or more symptoms were twice as likely as asymptomatic
      patients to have a satisfaction score of less than 8 (P <.001). CONCLUSIONS:
      Ocular dryness symptoms occurred commonly after PRK and LASIK. Symptoms
      suggestive of mild recurrent erosions included sharp pains, the sensation of the
      eyelid sticking to the eyeball, and soreness of the eyelid to touch, a previously
      unrecognized symptom of this condition. These symptoms occurred commonly after
      excimer laser procedures but were significantly more common, more severe, and
      more prolonged after PRK. The presence of these symptoms had a significant effect
      on patient satisfaction.

PMID- 11311628
TI  - Ascorbic acid levels in human tears after photorefractive keratectomy,
      transepithelial photorefractive keratectomy, and laser in situ keratomileusis.
AB  - PURPOSE: To investigate the level of ascorbic acid in human tear fluid after
      photorefractive keratectomy (PRK), transepithelial PRK, and laser in situ
      keratomileusis (LASIK). SETTING: Departments of Ophthalmology and Biochemistry,
      School of Medicine, Gazi University, Ankara, Turkey. METHODS: Twenty patients (7
      women and 13 men) were included in this study. Traditional PRK with epithelial
      scraping by a blunt spatula followed by surface ablation (7 eyes),
      transepithelial PRK (7 eyes), or LASIK (6 eyes) was performed. Tears were
      collected preoperatively and 1 and 5 days postoperatively. Ascorbic acid levels
      were measured using 2-4 dinitrophenylhydrazine. RESULTS: Ascorbic acid levels in
      the tear fluid were decreased significantly 1 day after PRK, transepithelial PRK,
      and LASIK (P <.05). On the fifth day, the ascorbic acid levels were significantly
      lower than preoperatively in all groups. CONCLUSION: After PRK, transepithelial
      PRK, and LASIK, the ascorbic acid levels of the tear fluid decreased
      significantly. Because ascorbic acid is the major scavenger of superoxide
      radicals in tears, topical ascorbic acid therapy may help eliminate the harmful
      effect of free radicals from excimer laser surgery.

PMID- 11311629
TI  - Corneal topography changes after a 15 second pause in blinking.
AB  - PURPOSE: To examine the effect of a short pause in blinking on the quantitative
      topographic parameters of the corneal surface. SETTING: Refractive corneal
      surgery unit of a university eye hospital. METHODS: Using a TMS-1 instrument
      (Computed Anatomy, Inc.), corneal topographic parameters were measured 5 and 15
      seconds after a complete blink in 12 healthy subjects. The main outcome measures
      were changes in the surface regularity index (SRI) and the surface asymmetry
      index (SAI). RESULTS: During the pause in blinking, the mean SRI value increased
      from 0.18 +/- 0.19 (SD) to 0.30 +/- 0.19 (P <.02) and the SAI from 0.21 +/- 0.08
      to 0.24 +/- 0.10 (P =.079, not statistically significant). There were no
      significant changes in the values for potential visual acuity, corneal refractive
      power, or astigmatism. CONCLUSION: The results indicated a significant change in
      corneal topography during even a short pause in blinking. In follow-up studies
      using corneal topography, all measurements should be done at a fixed time after a
      complete blink.

PMID- 11311630
TI  - Safety and predictability of laser in situ keratomileusis enhancement by flap
      reelevation in high myopia.
AB  - PURPOSE: To evaluate the safety and predictability of laser in situ
      keratomileusis (LASIK) retreatment following primary procedures for high myopia
      and astigmatism. SETTING: Corneal Diseases and Excimer Laser Research Unit,
      Department of Ophthalmology, University of Dundee, Dundee, United Kingdom.
      METHODS: This prospective observational study of retreatment comprised a cohort
      of 109 eyes having primary LASIK for high myopia and astigmatism with a spherical
      equivalent (SE) of -9.70 diopters (D) +/- 4.06 (SD). Twenty-four eyes (22%) with
      an initial myopic SE of -9.83 +/- 3.50 D, a comparable subset of the entire group
      (P < .05), had retreatment for residual myopia (-3.02 +/- 2.17 D) to improve
      uncorrected visual acuity (UCVA) by reelevating the corneal flap and ablating the
      stromal bed. RESULTS: The mean follow-up after retreatment was 12.8 +/- 5.1
      months (range 1.5 to 24 months; 19 eyes >/=6 months, 13 eyes > or = 12 months).
      The mean myopic SE was reduced to +0.53 +/- 0.62 D at 1 week, +0.05 +/- 0.50 D at
      1 month, +0.30 +/- 0.50 D at 6 months, and +0.18 +/- 0.42 D at the latest follow
      up, 12.8 months. At the latest review, 62% of eyes were within +/-0.50 D of
      emmetropia and 100% were within +/-1.00 D. The mean refraction did not alter
      statistically between 1 week and subsequent times. The mean UCVA improved from
      6/30 prior to retreatment to 6/9 at the latest follow-up. Uncorrected visual
      acuity of 6/6 or better, 6/9 or better, and 6/12 or better was achieved by 33.0%,
      75.0%, and 95.8% of eyes, respectively. No significant complications that led to
      a loss of best corrected visual acuity were encountered, although retreatment
      procedures were more uncomfortable than primary procedures and self-limiting;
      epithelial ingrowth that did not threaten vision was common, and 2 patients
      complained of nighttime visual symptoms. CONCLUSIONS: Retreatment of residual
      myopia by reelevating the flap was relatively safe and predictable, with a low
      risk of sight-threatening complications. However, longer term studies may be
      required to detect late complications.

PMID- 11311631
TI  - Respirable particles in the excimer laser plume.
AB  - PURPOSE: To determine whether respirable-size particles are present in the
      excimer laser plume following ablation of the corneal stroma. SETTING: Outpatient
      laser vision correction facility. METHODS: In this experimental study, an excimer
      laser was used to ablate 2 eye-bank corneas. Material from the plume was
      collected with filter paper that was coupled to a smoke evacuator. The filter
      paper was examined and photographed with an electron microscope. The particle
      size was measured with a computer program using digitized images of the
      photographs. As a control, room air was sampled using a smoke evacuator connected
      to a holder containing filter paper prior to the tissue ablation. RESULTS: Ninety
      eight particles were measured. The mean diameter was 0.22 microm +/- 0.056 (SD).
      No particles were seen on the control filter paper. CONCLUSIONS: The plume
      created during excimer laser ablation of the cornea contained respirable-size
      particles. It is not known whether inhalation of these particles poses a
      significant health hazard. However, we recommend that a mask be worn by the
      surgeon and technical personnel assisting in excimer laser surgery. The plume
      should also be evacuated.

PMID- 11311632
TI  - Effect of round-edged acrylic intraocular lenses on preventing posterior capsule
      opacification.
AB  - PURPOSE: To clarify the extent to which the adhesiveness of an acrylic material
      influences the formation of posterior capsule opacification (PCO). SETTING:
      Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS: Two
      types of AcrySof(R) intraocular lenses (IOLs) were prepared: round edged and
      tumbled. The AcrySof with round edges was implanted in 1 eye in a group of 4
      rabbits and the tumbled IOL, in 1 eye in a group of 5 rabbits. In both groups,
      the contralateral eye received a conventional AcrySof with sharp optic edges. A
      histopathological examination was performed 3 weeks after surgery. RESULTS: With
      the round-edged AcrySof IOL, no capsular bend formed at the optic edge and
      abundant lens epithelial cells (LECs) migrated posteriorly. With the sharp-edged
      AcrySof lens, a sharp capsular bend formed and LEC migration was significantly
      inhibited. In eyes with a tumbled IOL, a capsular bend was created, but it was
      less marked than that created by the sharp-edged lens and there was slightly more
      LEC migration posteriorly. CONCLUSIONS: The AcrySof IOL lost its preventive
      effect on PCO when the optic was rounded. The effect of the AcrySof lens in
      preventing PCO is mainly a result of its rectangular, sharp-edged optic design.
      The acrylic material may play a complementary role by helping create a sharp
      capsular bend. Capsular bend formation is the key to the PCO preventive effect of
      an IOL.

PMID- 11311633
TI  - Analysis of postoperative glare and intraocular lens design.
AB  - PURPOSE: To assess the potential for reflected glare images from commonly used
      intraocular lens (IOL) materials and designs. SETTING: Mayo Clinic, Rochester,
      Minnesota, USA. METHODS: The interaction of reflected light rays from 3 commonly
      used IOLs (Bausch & Lomb LI61U and P359UV; Alcon AcrySof(R) MA60BM) with
      different optic designs (equi-biconvex: 10.0 and 15.0 mm anterior radius of
      curvature; unequal biconvex: 32.0 mm anterior radius of curvature) and optic
      materials (silicone, poly[methyl methacrylate], and acrylic) were examined in an
      eye model using the Zemax optical design program. The potential of each IOL model
      to produce subjective glare was determined from the size of the defocused
      reflected glare image at the retina. RESULTS: The unequal biconvex design
      concentrated reflected light on a retinal area that was 60-fold smaller than that
      of the equi-biconvex design. Increasing the refractive index of the IOL material
      from 1.43 (silicone) to 1.55 (acrylic) increased the amount of reflected light 5
      fold. Compared to an equi-biconvex design composed of a lower refractive index
      material, the unequal biconvex design with a higher refractive index material
      increased the relative intensity of reflected light at the retina 300-fold, and
      for eyes with low corneal power the intensity increased 3500-fold. Similarly, for
      external glare apparent to an outside observer, the intensity of reflected light
      increased 400-fold and for low corneal power it increased 6000-fold. CONCLUSION:
      An unequal biconvex IOL design (32.0 mm anterior radius of curvature) composed of
      a higher refractive index material increased the potential for postoperative
      glare and external reflections.

PMID- 11311634
TI  - Corneal complications associated with topical ophthalmic use of nonsteroidal
      antiinflammatory drugs.
AB  - PURPOSE: To explore the potential association between adverse corneal events and
      the use of topical nonsteroidal antiinflammatory drugs (NSAIDs). SETTING:
      Practice-based reports. METHODS: A detailed case-reporting form and request for
      medical records were sent to all practices reporting cases of corneal or
      conjunctival pathology in association with the use of topical NSAIDs to the
      American Society of Cataract and Refractive Surgery. Cases were classified as
      "mild," "moderate," or "severe" according to predetermined clinical criteria.
      RESULTS: Records of 140 eyes (129 patients) were reviewed; 51 cases (36.4%) were
      mild, 55 (39.3%) moderate, and 34 (24.3%) severe. An association with a specific
      topical NSAID was confirmed in 117 cases (81.8%). Most confirmed cases (53.8%)
      involved generic diclofenac (Falcon). Cases associated with brand diclofenac
      (Voltaren, CIBA Vision) and ketorolac (Acular, Allergan) were more likely to have
      ocular comorbidity and to have received significantly higher total doses of
      NSAIDs. Neither "off-label" use nor use of any specific agent was associated with
      severe compared to mild or moderate disease. However, patients with more severe
      adverse events were more likely to have a history of diabetes, previous surgery
      in the affected eye, and surgery other than cataract. Cases not occurring in the
      perioperative period had significantly worse outcomes, had significantly more
      ocular comorbidities, and received nearly 3 times the dose of NSAIDs.
      CONCLUSIONS: While topical NSAIDs as a class may be associated with severe
      adverse events, such events appeared to require potentiation in the form of high
      total doses, ocular comorbidities, or both with Acular and Voltaren. Severe
      adverse events might have been more likely to occur at lower doses and in routine
      postoperative settings with generic diclofenac.

PMID- 11311635
TI  - Combined refractive lensectomy and laser in situ keratomileusis to correct
      extreme myopia.
AB  - Refractive lensectomy followed by laser in situ keratomileusis (LASIK) was
      performed in both eyes of a severely myopic patient. An uncorrected visual acuity
      of 20/20 was achieved in the right eye with a manifest refraction of plano -0.25
      x 65. Intentional monovision correction of the left eye left a manifest
      refraction of -0.75 diopter. Best corrected visual acuity improved by 1 Snellen
      line to 20/20 in both eyes. Follow-up evaluation will be required to assess the
      long-term refractive stability and the incidence of retinal detachment after
      combined refractive lensectomy and LASIK.

PMID- 11311636
TI  - Laser in situ keratomileusis in an eye with congenital nystagmus.
AB  - A 38-year-old man with congenital nystagmus had laser in situ keratomileusis
      (LASIK) to correct a spherical equivalent of -11.0 diopters (D) in the right eye
      and -10.0 D in the left eye. Baseline uncorrected visual acuity (UCVA) was 20/400
      in both eyes, and best spectacle-corrected visual acuity was 20/60 in the right
      eye and 8/20 in the left. The procedure was performed using the Aesculap Meditec
      MEL 60 excimer laser system and a semicircular suction ring device. Six months
      after LASIK, the patient had a UCVA of 20/60 in the right eye and 8/20 in the
      left eye, with no improvement with spectacle correction. Laser in situ
      keratomileusis can be performed with a semicircular suction ring device to
      correct refractive errors in patients with congenital nystagmus, but more cases
      have to be performed to confirm that the device is safe and suitable for these
      patients.

PMID- 11311637
TI  - Viscoelastic material as an adjunct to dissections and to treat microperforations
      during nonpenetrating filtering surgery.
AB  - A case is described in which viscoelastic material was used in the anterior
      chamber to minimize or prevent fluid flow through the area of the trabecular
      meshwork and Schlemm's canal during nonpenetrating filtering surgery. In cases
      with or without small perforations, the technique minimizes or decreases fluid
      flow so that the surgeon has a clearer view of these tissues and can perform more
      thorough and accurate stripping of deeper layers of tissue.

PMID- 11311638
TI  - Pigment dispersion with elevated intraocular pressure after AcrySof intraocular
      lens implantation in the ciliary sulcus.
AB  - A 45-year-old white woman had phacoemulsification with intraocular lens (IOL)
      implantation. The surgery was routine except for a linear tear in the posterior
      capsule; there was no disruption of the anterior vitreous face. After residual
      soft lens matter was removed, an AcrySof IOL was placed in the ciliary sulcus.
      One month postoperatively, the patient presented with an intraocular pressure
      (IOP) of 30 mm Hg and signs of pigment dispersion with 360 degrees of heavy
      pigmentation of the trabecular meshwork and iris transillumination defects.
      Intraocular pressure was controlled with a topical beta-blocker. The optic disc
      appearance and visual field remained normal, but the uniocular hyperpigmentation
      of the trabecular meshwork was still present. We hypothesize that the sharp
      square edge of the AcrySof IOL increases the risk of a chafing effect on the
      posterior iris pigment and advocate that this IOL be placed in the capsular bag
      and ideally have 360 degrees of protective overlapping of the anterior capsule
      over the edge of the optic.

PMID- 11311639
TI  - Childhood cancer survival in Europe, 1978-1992: the EUROCARE study.

PMID- 11311640
TI  - The EUROCARE study of survival of cancer patients in Europe: aims, current
      status, strengths and weaknesses.

PMID- 11311641
TI  - Childhood malignancies in the EUROCARE study: the database and the methods of
      survival analysis.
AB  - This paper describes the database of children with cancer in the EUROCARE study
      and the methodology used to analyse and report survival. This is the first
      systematic evaluation of survival after childhood cancer on a large scale in
      Europe: approximately 45,000 cases were included, diagnosed between 1978 and 1992
      (34,814 cases diagnosed in 1978--1989 and an additional set of 9495 cases
      diagnosed in 1990--1992) and followed-up until 1995. Data were provided from 34
      population-based registries (four specialised for childhood cancer registrations
      and one specialised registry for childhood leukaemia) in 17 countries of Europe
      (where there was national coverage in 10 countries). Quality of the data was
      fairly good, given the general differences among the countries and their health
      systems, thereby allowing for comparisons between them. Among cases diagnosed in
      1978--1989, overall 2.0% were lost to follow-up, 91.8% were microscopically
      diagnosed and 93.4% of alive cases had at least 5 years of observation. Survival
      proportions (observed survival) were calculated for each of the countries
      involved, by age group (0, 1--4, 5--9, 10--14 years), gender, different time
      periods and selected diagnostic groups. Age-standardised cumulative survival
      rates and European averages (weighted and pooled) were also computed. Cox
      regression models were used to evaluate geographical and temporal differences.
      The EUROCARE database represents a unique source of information on survival of
      childhood cancer patients in Europe, intercountry differences and time trends in
      survival.

PMID- 11311642
TI  - Variation in survival of European children with acute lymphoblastic leukaemia,
      diagnosed in 1978--1992: the EUROCARE study.
AB  - The aim of this study was to provide a comparative description of geographical
      variations and time trends in the population-based survival of European children
      with acute lymphoblastic leukaemia (ALL). Data on 13344 newly diagnosed children
      (0--14 years) with ALL were included in the EUROCARE study and were collected
      were collected by 34 population-based cancer registries (four comprising only
      childhood malignancies), operating in 17 countries (four in Scandinavia, two in
      Southern Europe, three in Eastern Europe, six in Continental Europe and two in
      the UK). Age-specific crude survival rates were estimated for boys and girls
      according to country for the period 1985--1989 and in adjusted form to attain
      comparability. Overall pooled and weighted rates were estimated as European
      standards. Children dead at diagnosis or diagnosed only through a death
      certificate were excluded. Geographical variation was also estimated by
      calculating the relative death rate with respect to the pooled overall European
      rate. After adjustment for age, gender and country, a Cox regression analysis was
      used to estimate time trends in survival. Survival was compared with that in the
      USA, Japan, Canada and Australia. During 1985--1989, the 1-year survival rate
      varied from 99 to 79%, the 5-year survival rate from over 80 to 56% (with the
      exception of Estonia; 34%; 95% confidence interval (CI) 20--52) among the various
      countries; the European weighted means were 90 (95% CI 87--93) and 72% (95% CI 69
      -75), respectively. Survival was particularly favourable in (south) Sweden,
      Finland, Germany and The Netherlands and rather unfavourable in Estonia and
      (surprisingly) France, where only 4% of its population was covered by the
      participating registries. Compared with the period 1978--1981, the hazard ratio
      for the period 1986--1989 decreased to 0.59 (95% CI 0.54--0.64) and -- in a
      smaller set of registries -- to 0.49 (0.45--0.55) for 1990-1992, an annual
      decrease in this rate of approximately 3.5%. During 1985--1989, the 5-year
      survival rates for European children were largely similar to those found in the
      USA, Canada and Australia, but markedly better than those in Japan. Higher
      survival rates were found for countries with 'good' access to centrally organised
      diagnostic and treatment facilities which stimulated 'aggressive' treatments
      according to a protocol. However, a subdivision according to risk profiles, e.g.
      according to the initial white blood cell count at diagnosis, could not be made
      and this might have explained partially the geographical differences in survival,
      because a positive association appeared between incidence at age 1--4 years and 5
      year survival in most countries.

PMID- 11311643
TI  - Survival from acute non-lymphocytic leukaemia (ANLL) and chronic myeloid
      leukaemia (CML) in European children since 1978: a population-based study.
AB  - We used data supplied by population-based cancer registries, collected and
      quality controlled using a common protocol, to analyse survival from acute non
      lymphocytic leukaemia (ANLL) and chronic myeloid leukaemia (CML) among children
      in 17 European countries. Variations in survival in relation to age, country,
      histologic subtype and period of diagnosis (1978--1992) were examined. These are
      rare malignancies and survival can be studied reliably only by examination of
      data from a very large population (in this case EUROCARE). 5 years after
      diagnosis, overall survival was 44% (95% CI 33--55) for CML and 37% (95% CI 32-
      43) for ANLL. For both types of leukaemia, survival was slightly better for girls
      and worse in children under 5 years of age. Consistent with clinical literature,
      the ANLL subtypes with poorer prognosis were monocytic, megakaryocytic and
      erythroleukaemia. For ANLL, 5-year survival was better in Finland, the UK, The
      Netherlands and Germany (> or =40%); for CML, 5-year survival was highest in
      Italy, although the 95% CI were wide. The risk of death from ANLL and CML fell by
      7% per year and 5% per year, respectively, after adjustment for age, gender and
      country. Since these rare childhood malignancies were virtually untreatable until
      1970, these are very welcome trends.

PMID- 11311644
TI  - Survival of childhood lymphomas in Europe, 1978--1992: a report from the EUROCARE
      study.
AB  - In most developed countries, malignant lymphomas account for 10--15% of all
      cancers occurring among children aged 0--14 years. The present study estimates
      survival after a diagnosis of lymphoma in childhood, based on the EUROCARE II
      database which includes 34 population-based cancer registries from 17 European
      countries. The survival pattern of children with malignant lymphoma diagnosed in
      1985--1989 is reported, as well as the time trends since 1978. The analyses focus
      on Hodgkin's disease (HD, 1696 cases) and on non-Hodgkin's lymphoma (NHL, 2255
      cases including Burkitt's lymphoma and unspecified lymphomas). For HD, the
      European weighted average 5-year survival rate was 93% (95% confidence interval
      (CI) 82--98) in 1985--1989. The survival rates were not affected by either age or
      gender. 5-year survival rates ranged from 68% (95% CI 34--90) in Estonia to 96%
      (95% CI 92--98) in Germany and 100% (95% CI 57--100) in Slovenia. Multivariate
      analyses for the time period 1978--1989 gave little suggestion of an improvement
      in survival over the later time periods of diagnosis. For NHL, the European
      weighted average 5-year survival rate was 74% (95% CI 67--80) in 1985--1989.
      Gender did not influence the survival rate. Children in the age group 0--4 years
      had a poorer prognosis compared with older cases (5-year rate: 66% versus 77% in
      the pool). 5-year survival rates ranged from 53% (95% CI 30--76) (Estonia) to 83%
      (95% CI 62--94) in France and 83% (95% CI 66--92) in Scotland. Multivariate
      analysis show a decreasing HR for the more recent periods of diagnosis from 1 in
      1978--1981 to 0.67 (95% CI 0.56--0.79) in 1982--1985 to 0.48 (95% CI 0.40--0.57)
      in 1986--1989. Exploratory analysis, conducted including the cancer registries
      which provided cases diagnosed until 1992, show a positive trend over time for
      both types of lymphoma.

PMID- 11311645
TI  - Variation in survival of children with central nervous system (CNS) malignancies
      diagnosed in Europe between 1978 and 1992: the EUROCARE study.
AB  - EUROCARE is a population-based survival study including data from European Cancer
      Registries. The present paper analyses survival after a malignant neoplasm of the
      central nervous system (CNS) in childhood (aged 0--14 years at diagnosis). The
      database includes 6130 cases from 34 population-based registries in 17 countries:
      1558 were primitive neuroectodermal tumours (PNET) and 4087 astrocytoma,
      ependymoma or other gliomas: these morphologies were grouped in the analyses in
      order to reduce the diagnostic variability among the registries. 87% of cases
      were microscopically diagnosed (range among registries 71--100%) and losses to
      follow-up were limited to 2% (range 0--14%). Actuarial analyses indicate that the
      European (weighted) average of 5 years cumulative survival for cases diagnosed in
      1978--1989 was 53% (95% confidence interval (CI) 49--57) for CNS neoplasms, 44%
      (95% CI 37--50) for PNET and 60% (95% CI 55--65) for the glioma-related types.
      Analysis of the sub-set of cases diagnosed in 1985--1989 revealed better results:
      cumulative survival at 5 years was 61% (95% CI: 55--65) for all CNS neoplasms;
      48% (95% CI 41--56) for PNET and 68% (95% CI 62--73) for glioma-related types.
      Compared with older children, infants showed poorer prognosis: in 1978--1989 the
      5-year survival rate was 33% (95% CI 23--45) and in 1985--1989 it was 46% (95% CI
      34--59). Variability among countries was very large, with 5-year survival for CNS
      tumours diagnosed in 1985--1989 ranging from 28% in Estonia (95% CI 17--43) to
      73% Sweden (95% CI 59--83) and 75% in Iceland (95% CI 35--95) and 73% in Finland
      (95% CI 66--79). Time trends were studied in a multivariate analysis observing a
      reduction in the risk of death in periods of diagnosis 1982--1985 (hazard ratio
      (HR)=0.85; 95% CI 0.78--0.93) and 1986--1989 (HR=0.70; 95% CI 0.64--0.77)
      compared with 1978--1981. The analysis were extended to 1990--1992 for the
      countries whose registries provided data for that period did not indicate any
      further progress. Results of this study confirm the large variability in European
      countries and indicate a positive trend in the survival probability for cases
      diagnosed in the 1980s.

PMID- 11311646
TI  - Survival of children with neuroblastoma. time trends and regional differences in
      Europe, 1978--1992.
AB  - Neuroblastoma is one of the most common solid cancers in children. We present the
      data collected for the EUROCARE II study, describing survival patterns for
      children diagnosed in Europe 1985--1989 in detail, and exploring time trends from
      1978 to 1992. On average, the mean 5-year survival rate was considerably higher
      in infants (79%) compared with older children (30--33%). The risk of death has
      dropped by 37% from 1978--1981 to 1990--1992. There is a pronounced difference
      between countries, with Scotland and England and Wales having two of the lowest
      survival rates (28% (95% confidence interval (CI) 14--48) and 36% (95% CI 31--41)
      5-year survival rates, respectively). The survival rates in France, Germany and
      Italy (48--66% 5-year survival rate) were among the highest. This pattern
      corresponds to the incidence rates for these countries. It can be assumed that in
      neuroblastoma, both incidence and survival are related to the frequency of
      diagnosing asymptomatic cases with good prognosis among infants. However, one
      cannot ignore possible intercountry differences in the effectiveness of therapy.

PMID- 11311647
TI  - Survival for retinoblastoma in Europe.
AB  - The survival of 954 cases of retinoblastoma, diagnosed between 1978 and 1989 in
      28 populations belonging to 17 European countries and covered by cancer
      registration, is analysed in this study. Data were collected in the framework of
      the EUROCARE study following a common protocol and data-check procedures and were
      analysed centrally by the Kaplan-Meier method and by the Cox regression model.
      Overall 5-year survival in the European pool was 93% (95% confidence interval
      (CI): 91--95%), for both sexes. Five-, 10- and 18-year survival for a subset of
      235 patients diagnosed in 1978--1981 was 91, 89 and 86%, respectively. Children
      diagnosed in their first year of age had a slightly higher survival (94%) than
      those diagnosed subsequently (92%). Survival rates lower than the European
      average were found in the Eastern European countries, Italy, England and Wales,
      Scotland, Spain and Denmark. Higher survival was found in the other Nordic
      countries and in Central European countries. However, none of these differences
      was statistically significant. There was statistically significant effect related
      to the period of diagnosis, with a 50% reduction in the relative risk (RR) for
      children diagnosed in 1986--1989 compared with those diagnosed in 1978-1981.

PMID- 11311648
TI  - Survival of children with Wilms' tumour in Europe.
AB  - A total 2535 cases of Wilms' tumours registered in children aged 0--14 years by
      34 population-based cancer registries in 16 countries of Europe in 1978--1992 and
      followed-up until the end of 1994 were included in this EUROCARE study. Overall 5
      year observed survival of all children diagnosed in 1985--1989 was 83%, 95%
      confidence interval (CI) 80--85. Relatively large differences were observed
      between the European countries, with significantly lower survival of patients
      registered in the formerly socialist countries, Estonia, Poland and Slovakia.
      Overall European survival was slightly lower in comparison with results reported
      from the USA and Australia, which demonstrate a potential for improvement. Over
      the study period, overall survival adjusted for age, sex and country has
      increased significantly. This favourable trend is attributed primarily to
      improvements in treatment, particularly to the introduction of new
      chemotherapeutic agents.

PMID- 11311649
TI  - Survival of children with liver tumours in Europe 1978--1989.
AB  - Hepatic tumours are rare in childhood. Within the frame of the EUROCARE II study,
      a total of 328 liver tumours in patients aged 0--14 years were reported during
      the period 1978--1989. The childhood cancer registries in UK and Germany
      contributed approximately a third of the cases each. Hepatoblastoma accounted for
      71% of cases. The 5-year survival was 36% 95% confidence interval (CI) 28--46%,
      with no significant difference between the genders. Patients aged 10--14 years
      did worse, especially boys. Survival improved significantly during the study
      period. Survival in hepatocellular carcinoma was lower, 20% (95% CI 6--52%), and
      showed no improvement during the study period.

PMID- 11311650
TI  - Survival of children with malignant germ cell, trophoblastic and other gonadal
      tumours in Europe.
AB  - Collaborators of the EUROCARE study had provided records on 1263 cases of germ
      cell, trophoblastic and other gonadal neoplasms, registered in 34 cancer
      registries in 16 European countries over the period 1978--1992 and followed-up
      until the end of 1994. Observed 5-year actuarial survival for 490 cases diagnosed
      in 1985-1989 was 80% (95% confidence interval (CI)=(76, 83)). The corresponding
      figures were calculated for the intracranial and intraspinal germ cell tumours
      (68%, 95% CI=(57, 76)), other non-gonadal germ cell tumours (76%, 95% CI=(68,
      82)), gonadal germ-cell tumours (89%, 95% CI=(85, 93)) and gonadal carcinomas
      (50%, CI=(24, 76)). Relatively large differences in survival were observed
      between age-sex subgroups, which also differed with histology, with extremely
      poor survival of young children with intracranial and intraspinal germ cell
      tumours. Lower survival was observed in the countries with formerly socialist
      economies. Time trends in survival were examined for the entire study period,
      including only the cases registered in the large contributing registries. For all
      germ cell tumours, the risk ratios calculated in the Cox regression analysis were
      markedly lowered for the years after the reference period of 1978--1981. The
      improved outcome is attributed to treatment advances.

PMID- 11311651
TI  - Survival of children with bone sarcoma in Europe since 1978: results from the
      EUROCARE study.
AB  - Malignant bone tumours in children are rare, accounting for approximately 5% of
      all childhood cancers in European countries. In the EUROCARE childhood cancer
      study, there were 1785 registrations from 16 countries for bone cancers in
      patients aged 0--14 years during 1978--1989. Of this total, almost three-quarters
      were contributed by childhood cancer registries in Germany and the UK. Estimated
      5-year survival rates were 52% for osteosarcoma and 50% for Ewing's sarcoma over
      the entire study period and 60% for both diagnostic groups in 1985--1989. For
      osteosarcoma, survival rates increased substantially until about 1985, but then
      showed no further improvement. For Ewing's sarcoma, there was a steady increase
      throughout the study period. Improvements in survival which had previously been
      reported from individual countries and in clinical series are confirmed as having
      taken place throughout much of Europe on a population basis.

PMID- 11311652
TI  - Survival of children with soft-tissue sarcoma in Europe since 1978: results from
      the EUROCARE study.
AB  - Soft-tissue sarcomas account for 5--8% of all childhood cancers in European
      countries. In the EUROCARE childhood cancer study, there were 2163 registrations
      from 17 countries for soft-tissue sarcomas in patients aged 0--14 years during
      1978--1989. Of this total, three-quarters were contributed by childhood cancer
      registries in Germany and the UK. Age-standardised 5-year survival rates of
      children diagnosed during 1985--1989 were 65% (95% confidence interval (CI) 56-
      72) for rhabdomyosarcoma, 68% (95% CI 58--77) for fibrosarcoma, 78% (95% CI: 64-
      87) for other specified soft-tissue sarcomas except Kaposi's and 51% (95% CI 37-
      65) for 'unspecified' soft-tissue sarcomas. Survival rates increased steadily
      throughout the 12-year study period for all soft-tissue sarcomas combined, but
      the increase took place predominantly in the early 1980s for rhabdomyosarcoma.
      Improvements in survival which had previously been reported from individual
      countries and in clinical series are confirmed as having taken place throughout
      much of Europe on a population basis. In a supplementary analysis, there was
      little indication of a further improvement during 1990--1992.

PMID- 11311653
TI  - Survival of children with thyroid cancer in Europe 1978--1989.
AB  - Thyroid cancers are rare in childhood with between 0.4 and 1.5 cases per million,
      2--3 times as frequent in girls as in boys. However, following the Chernobyl
      accident, a remarkable incidence increase was observed in children exposed to
      radioactive iodine fall-out. Survival after thyroid cancer in childhood is thus
      of interest. In the EUROCARE II study, excluding most of Eastern Europe, a total
      of 165 childhood thyroid cancers were reported during the period 1978--1989, of
      which 134 were aged 10--14 years. The childhood cancer registry in England and
      Wales contributed 39% of the cases, and another 24% came from the Nordic
      countries, the rest from other parts of west, south, east and central Europe. The
      5-year survival was for both genders combined 97% (95% confidence interval (CI):
      93--99), 98% (95% CI: 91--100) for boys and 97% (95% CI: 91--99) for girls, with
      no significant difference between the genders. Survival was high during the
      entire study period, and variations influenced by the small numbers. As for
      adults, long-term follow-up beyond 10--20 years is needed to clearly demonstrate
      excess mortality as a consequence of the cancer.

PMID- 11311654
TI  - Childhood melanoma in Europe since 1978: a population-based survival study.
AB  - The existence of the EUROCARE database now makes it possible to compare
      population-based survival for childhood melanoma in different European
      populations. The database contains verified information, including histological
      data, from cancer registries in 17 European countries, and as such it represents
      a particularly important source of survival information on a very rare cancer
      like childhood melanoma. The aim of the present paper was to describe survival in
      children with melanoma (MM), by sex, age and subsite, diagnosed during the period
      1978--1989, using analysis of the data of the European pool of cases. Five year
      survival for childhood MM diagnosed in 1978--1989 in Europe, is relatively good
      (80%; 95% confidence interval (CI) 47--95 for boys and 78%; 95% CI 58--91 for
      girls). Analysis by subsite, revealed the survival for MM on the head and neck,
      legs and arms was generally higher than survival for MM on other cutaneous sites
      (trunk, neck and scalp). For skin melanomas outcome for girls was better than
      boys, adjusting for age and sub-site. We suggest that the good survival observed
      in childhood MM seems to be related to early diagnosis.

PMID- 11311655
TI  - Childhood cancer mortality in Europe, 1955--1995.
AB  - Childhood cancer (0--14 years) mortality rates for six cancer sites, including
      bone, kidney, eye, Hodgkin's disease, non-Hodgkin's lymphomas, leukaemias, plus
      total cancer mortality were computed for subsequent calendar periods from 1955 to
      1997, and graphically presented for 16 Western European countries, seven Eastern
      European countries, plus the European Union as a whole. All Western European
      countries showed substantial declines in mortality from leukaemias and from all
      neoplasms considered from the mid-1960s onwards, for an average fall over 60%,
      and an estimated total number of approximately 4500 avoided deaths per year.
      Favourable trends were observed also in Eastern Europe, but the declines started
      later (i.e. around the mid-1970s or the late 1980s), and were only approximately
      30%.

PMID- 11311656
TI  - Childhood cancer survival in Europe: an overview.
AB  - Other articles in this issue of the European Journal of Cancer have described
      population-based survival analyses of specific types of childhood cancer included
      in the EUROCARE database, diagnosed since 1979. The present paper summarises the
      relevant estimates and comments on intercountry differences, focusing on possible
      distortions in the intercountry comparisons based on data produced by the cancer
      registries. Potential biases include a lack of exhaustiveness of both case
      ascertainment and follow-up for living status and also a lack of consistency in
      the use of classification of the childhood cancer types. Nevertheless, despite
      such biases, consistent differences are observed between European countries in
      the probability of survival following the diagnosis of a paediatric cancer. In
      most cases, poor population-based survival rates are probably explained by
      inadequacies in the adoption and implementation of therapeutic protocols that
      have been proved to be effective. In some instances, the cause of unsatisfactory
      estimates was the inclusion of a sizeable proportion of children with cancer in
      clinical trials which were found to be ineffective. A regression analysis of
      incidence, mortality and survival rates during 1978-1989 over the whole EUROCARE
      database strongly indicates that the prognostic improvements over time are real
      and cannot be attributed to changes in diagnostic procedures.

PMID- 11311657
TI  - Molecular markers predictive of response to chemotherapy in gastrointestinal
      tumors.
AB  - Gastrointestinal cancers account for a large amount of human tumors. Surgery is
      the standard treatment for localized gastrointestinal cancer, but in a large
      number of patients, tumors are unresectable at time of diagnosis and even when
      resectable, survival is often poor. Current attempts to improve these results
      include the use of chemotherapy in the adjuvant setting, in the advanced disease,
      or as neoadjuvant treatment. However, less than half the patients respond to
      chemotherapeutic treatments, mostly reporting important side-effects. The
      identification of molecular markers, such as p53, thymidylate synthase, K-ras,
      and others, may provide an important tool for medical oncologists in defining
      subsets of patients with gastrointestinal cancers more suitable to benefit from
      chemotherapy or from experimental therapies. The relationship between the
      clinical outcome to anticancer drugs and molecular markers in gastrointestinal
      tumors has been reviewed. Available data are promising, but most of them arise
      from retrospective and small studies. Well designed, prospective trials are
      warranted to change the target approach from a general to an individual treatment
      strategy.

PMID- 11311658
TI  - Taxanes in lung cancer: a review with focus on the European experience.
AB  - The introduction of new agents in the treatment of lung cancer raised in the past
      few years new interest in clinical research on this topic. The use of taxanes as
      paclitaxel and docetaxel may represent a significant progress in the treatment of
      lung cancer. Taxanes used as single agents show a substantial activity in lung
      cancer and, because of their unique mechanism of action, it is possible to
      combine these drugs with other non-cross-resistant agents. Taxanes share a
      radiosensitizing effect and their use with concurrent radiotherapy appears to
      become a new standard. This review will focus on the European clinical experience
      in the treatment of lung cancer with the two compounds.

PMID- 11311659
TI  - New therapeutic modalities in the treatment of graft-versus-host disease.
AB  - Acute and chronic GvHD are still a major concern in allogeneic hematopoietic stem
      cell transplantation, still contributing substantially to morbidity and mortality
      in this therapeutic procedure. Over the past decade, many advances have been made
      with regard to the prevention and treatment of GvHD using various drugs such as
      cyclosporine A, FK506, mycophenolate mofetil and/or monoclonal IL-2 receptor
      antagonists. Despite these measurements with regard to the prevention of acute
      GvHD, it is very difficult to treat these clinical conditions successfully.
      However, if patients do not experience any GvHD often the desired effect of graft
      versus leukemia (GvL) remains absent increasing the probability of a relapse, in
      particular, in patients transplanted, which are considered at higher risk for
      relapse. At the present time, new strategies in the prevention of acute GvHD are
      in progress in particular the use of genetic manipulated donor T cells expressing
      suicide genes. Further clinical and laboratory studies are required in order to
      improve the prevention and, in particular, the therapy of established GvHD.

PMID- 11311660
TI  - Mechanisms of action of flavopiridol.
AB  - Flavopiridol inhibits phosphokinases. Its activity is strongest on cyclin
      dependent kinases (cdk-1, -2, -4, -6, -7) and less on receptor tyrosine kinases
      (EGFR), receptor associates tyrosine kinases (pp60 Src) and on signal transducing
      kinases (PKC and Erk-1). Although the inhibiting activity of flavopiridol is
      strongest for cdk, the cytotoxic activity of flavopiridol is not limited to
      cycling cells. Resting cells are also killed. This fact suggests that inhibition
      of cdks involved in the control of cell cycle is not the only mechanism of
      action. Inhibition of cdk's with additional functions (i.e. involved in the
      control of transcription or function of proteins that do not control cell cycle)
      may contribute to the antitumoral effect. Moreover, direct and indirect
      inhibition of receptor activation (EGFR) and/or a direct inhibition of kinases
      (pp60 Src, PKC, Erk-1) involved in the signal transduction pathway could play a
      role in the antiproliferative activity of flavopiridol. From pharmacokinetic data
      in patients it can be concluded that the inhibitory activity (IC50) of
      flavopiridol on these kinases is in the range of concentrations that might be
      achieved intracellularly after systemic application of non-toxic doses of
      flavopiridol. However, no in situ data from flavopiridol treated cells have been
      published yet that prove that by inhibition of EGFR, pp60 Src, PKC and/or Erk-1
      (in addition to inhibition of cdk's) flavopiridol is able to induce apoptosis.
      Thus many questions regarding the detailed mechanism of antitumoral action of
      flavopiridol are still open. For the design of protocols for future clinical
      studies this review covers the essential information available on the mechanism
      of antitumoral activity of flavopiridol. The characteristics of this antitumoral
      activity include: High rate of apoptosis, especially in leukemic cells; synergy
      with the antitumoral activity of many cytostatics; independence of its efficacy
      on pRb, p53 and Bcl-2 expression; lack of interference with the most frequent
      multidrug resistance proteins (P-glycoprotein and MRP-190); and a strong
      antiangiogenic activity. Based on these pharmacological data it can be concluded
      that flavopiridol could be therapeutically active in tumor patients: independent
      on the genetic status of their tumors or leukemias (i.e. mutations of the pRb
      and/or p53, amplification of bcl-2); in spite of drug resistance of their tumors
      induced by first line treatment (and caused by enhanced expression of multidrug
      resistance proteins); in combination with conventional chemotherapeutics
      preferentially given prior to flavopiridol; and due to a complex mechanism
      involving cytotoxicity on cycling and on resting tumor cells, apoptosis and
      antiangiogenic activity. In consequence, flavopiridol is a highly attractive, new
      antitumoral compound and deserves further elucidation of its clinical potency.

PMID- 11311661
TI  - Telemedicine in the Asia Pacific.

PMID- 11311662
TI  - The final report of the project 'AMINE' the Asia Pacific Medical Information
      Network using with ETS-V.
AB  - Volunteer groups led by the Tokai University School of Medicine and the
      Telemedicine Society of Japan (a Non-Governmental Organization) worked from 1992
      to 1996 to successfully develop a medical network spanning the Asia Pacific
      region using the ETS-V Satellite. The effort was part of the Partners project,
      sponsored by the Ministry of Posts and Telecommunications (MPT) and the National
      Space Development Agency of Japan. From 25 ground stations, links to the
      telemedical network were installed at medical institutions at no cost. The
      stations included five in Papua New Guinea, five in Thailand, four in Cambodia,
      four in Fiji, one in China, and six in Japan. Designed exclusively for medical
      applications, the network was operated free of charge for users at these sites.
      While the 16-kHz FM-based (Frequency Modulation-based) network limited
      applications to the transmission of color still images and audio and packet
      networking, the project still achieved impressive results. The network allowed
      liberal and independent use of international communications, local
      communications, teleconferences, and teleconsultations, without requiring a hub
      station.

PMID- 11311663
TI  - Moving with the sun.
AB  - A global 24-hour telemedicine conference entitled, "Moving with the Sun" was
      successfully completed on June 30 and July 1 1997 between participants from Hong
      Kong and China, as well as with sixteen major international medical centres
      around the globe. In addition to celebrating the return of Hong Kong to the
      People's Republic of China, the conference also signified the establishment of
      the Chinese University of Hong Kong, and Hong Kong as a bridge between Western
      countries and the PRC.

PMID- 11311664
TI  - The untapped potential of Telehealth.
AB  - The people of Malaysia generally enjoy a high standard of health. This is largely
      attributed to the comprehensive range of health services provided by the
      Government and the private sector at affordable costs. However, there are
      changing trends that now seriously challenge this status quo. The changing
      population structure, lifestyle, disease patterns and globalization are causing
      healthcare costs to rise. New and innovative ways will have to be devised to
      further improve the health status and at the same time contain costs. Information
      and Communication Technology (ICT) presents unprecedented opportunities to help
      the health sector in Malaysia reinvent itself and transform the way health and
      healthcare is managed and delivered in the future. Malaysia's Telehealth
      initiative under the Multimedia Super Corridor (MSC) project is designed to
      realize Malaysia's health vision and goals and meet future health challenges.
      Multimedia and Internet technology will be fully harnessed to deploy services
      that will shift the emphasis from episodic management of illness to proactive
      promotion of lifelong wellness and disease prevention. Health information content
      and interactive applications will engage the people to work as partners of health
      with healthcare professionals in maintaining their own health or managing their
      illnesses.

PMID- 11311665
TI  - The Ministry of Public Health telemedicine network of Thailand.
AB  - The concept of telemedicine is rather new in Thailand and initially, the
      introduction of telemedicine into the country was hampered by technological
      limitations. The problem was further aggravated by the inadequacy of
      telecommunications infrastructures in the rural areas. However, recent rapid
      advances in info-communications technology, together with the launch of
      Thailand's first communication satellite, THAICOM I in December 1993, have made
      it possible for health care to be delivered to remote areas of the country via
      telemedicine. This paper documents the experience of implementing Thailand's
      nationwide Telemedicine Network by the Ministry of Public Health (MOPH),
      beginning with a pilot project in 1994 to the current system, launched in January
      1998, that links the Information Technology Office of the MOPH and 19 hospitals
      with health facilities all over the country via satellite and computer networks.

PMID- 11311666
TI  - Review of telemedicine projects in Taiwan.
AB  - Taiwan is a heavily populated country, with a small land area and many mountains
      and isolated islands. Because medical resources are unequally distributed, high
      quality accessible medical care is a major problem in rural areas. Medical
      personnel are unwilling to practice in rural areas because of fear of isolation
      from peers and lack of continuing medical education (CME) in those areas.
      Telemedicine provides a timeless and spaceless measure for teleconsultation and
      education. The development of telemedicine in Taiwan began under the National
      Information Infrastructure (NII) Project. Distance education and teleconsultation
      were the first experimental projects during the initiation research stage. The
      cost and effectiveness of the hardware and network bandwidth were evaluated. In
      the promotion research stage, applications in different medical disciplines were
      tested to promote multipoint videoconference, electronic journals and VOD.
      Investigation of user satisfaction put on more emphasis on improving application
      functions. In 1998, a new Cyber Medical Center (CMC) international collaboration
      project was begun, integrating technologies of multimedia, networking, database
      management, and the World Wide Web. The aim of the CMC is to create a multimedia
      network system for the management of electronic patient records,
      teleconsultation, online continuing medical education, and information services
      on the web. A Taiwan mirror site of Virtual Hospital and two international
      telemedicine trials through Next Generation Internet (NGI) were done at the end
      of 1998. In the future, telemedicine systems in Taiwan are expected to combine
      the Internet and broadband CATV, ADSL, and DBS networking to connect clinics,
      hospitals, insurance organizations, and public health administrations; and,
      finally, to extend to every household.

PMID- 11311667
TI  - The present and future of telemedicine in Japan.
AB  - Telemedicine has always developed in close relation with communication
      technology. When only aural telephones were used, several experiments of
      telemedicine were carried out by utilizing telephone lines. When INS64 (ISDN with
      64 kbits) and telecommunication satellites came onto the scene, experiments for
      telemedicine began to be conducted accordingly using the cutting-edge technology
      of the time. In this paper, one of the three categories of telemedicine, mainly
      tele-consultation that includes tele-pathology and tele-radiology, will be
      discussed with some examples conducted in Japan. As time goes on, the aim of
      telemedicine has also been changing. In 1996, the Japanese government gave the go
      ahead for telemedicine along its deregulation policies. Telemedicine including
      tele-home care in the 21st century will use the Internet and digital HDTV (high
      definition TV) technology for information and data management interchangeably
      both at domestic and global levels in the medical environment. Also, our dream of
      a hyper-hospital or virtual hospital will be realized in cyberspace before long,
      but first we may have to overcome several tough problems such as the protection
      of privacy data, malpractice and vulnerability of technology relevant to the
      Internet and telecommunications satellite system as a whole.

PMID- 11311668
TI  - Telemedicine in China.
AB  - Telemedicine has been shown to have a considerable impact in medical education,
      conferencing and consultation. As a result, the People's Republic of China has
      been keen to develop telemedicine. In her attempts to further the development of
      telemedicine, China has looked to the progress of medical services in Western
      countries such as Europe and North America. The United States of America,
      however, has exceeded the rest in exchange of health-care information and
      telemedicine technologies with China. Although China has been enthusiastic about
      the exchange, telemedicine in China requires development in the technical
      infrastructure and professional infrastructure.

PMID- 11311669
TI  - Hospital and emergency ambulance link: using IT to enhance emergency pre-hospital
      care.
AB  - Emergency ambulances traditionally inform receiving hospitals of impending
      arrival of patients only in instances of load and go situations, which on average
      constitute less than 5% of ambulance runs. Information transmitted is usually
      sparse. For all other runs, information is made available only on arrival at the
      emergency department (ED). There have also been numerous limitations associated
      with voice transmissions.A comprehensive electronic ambulance case record was
      created as a pilot project in Singapore between three emergency ambulances and
      the busiest ED there. All information captured by the ambulance crew, including
      vital signs information and ECGs was entered or downloaded onto a ruggardised PC
      in the ambulance and this complete ambulance record was transmitted to the ED.
      Transmission was wireless via the public mobile data network. A 3-month analysis
      of this pilot run revealed the following. (1) It was possible to capture a
      complete ambulance case record electronically at a mean time of 94 s vs 7 min 7 s
      for the traditional written record. (2) Air transmission time for data was
      approximately 4 s unless ECG wave forms were also transmitted resulting in
      transmission times frequently exceeding 60 s. (3) At least 68% of data was
      transmissible in 75% of Hospital & Emergency Ambulance Link (HEAL) ambulances as
      opposed to only 25% in less than 5% of non-HEAL ambulances. (4) Paramedics' time
      in the ED decreased from 15 to 8 min as a result of HEAL. (5) The waiting time
      for critical care patients to be seen at the ED decreased from 35 to 17 min if
      brought by HEAL ambulances.(6) The HEAL system was able to effectively prompt
      paramedics in carrying out critical aspects of treatment in close to 100% of
      instances. (7) The pilot HEAL system was able to demonstrate a limited amount of
      automated audit of specific aspects of ambulance runs. Having demonstrated the
      feasibility of the HEAL system, it is a matter of time before enhanced features
      such as electronic data collection at patient site, voice activated data entry,
      transmission of data from site, automated ambulance audits and an enhanced level
      of professional care in the ambulances become common-place reality.

PMID- 11311670
TI  - Current status and history of teleradiology in India.
AB  - Teleradiology is yet to take off in India. This is unfortunate since this
      technology is ideal for a country like India, where expertise in remote areas for
      advanced investigations such as CT and MR, is lacking. We were the first center
      in India to use teleradiology on a regular basis. Our initial methodology in 1996
      was using video-capture cards and Windows 95 dial-up protocols. Now we use DICOM
      transfers and remote-access software. Even today, 4 years later, we are the only
      center in India using teleradiology on a regular basis.

PMID- 11311671
TI  - Patient satisfaction with telemedicine in home health services for the elderly.
AB  - In a pilot study of telemedicine in home health services (HHS) for elderly
      patients, we implemented and evaluated a telemedicine system with a 33-kbs narrow
      band approach to determine its effectiveness in providing quality services. Fifty
      patients were selected for the study. We found that telemedicine was effective in
      terms of reducing the number of clinic visits and achieving patient satisfaction.
      The average number of clinic visits per month was significantly decreased from
      0.64 to 0.42 (p < 0.05) after the use of telemedicine. 72% of patients were
      satisfied with telemedicine, but only patient location showed a significant
      difference for patient satisfaction (p < 0.05). Patients in their homes (82%)
      were more satisfied than patients in nursing homes (50%). Of four types of
      services provided, medical consultation (100%) was the most highly satisfactory
      service with telemedicine, followed by physical therapy (83.3%). Although the
      satisfaction scores did not indicate a significant difference in the system
      characteristics, the quality of verbal communication appeared to be a more
      important factor in influencing patient satisfaction than set-up time or quality
      of image. A computer-based patient record was also developed to view a patient
      summary and to document encounters at the patient's home. Since the system is a
      low-cost approach that is easy to interface with a notebook computer, it can
      support various other HHSs.

PMID- 11311672
TI  - Implementation and evaluation of a multifunctional telemedicine system in NTUH.
AB  - In this article, we proposed a multifunctional telemedicine system supporting
      both telediagnosis and teleconsultation services. We attempted not only to insure
      that the implementation of this system satisfied most requirements, but also to
      evaluate the impact of the system. With regard to system architecture, we
      designed a unified multimedia database to store all types of data and used two
      kinds of network (ATM and ISDN) for different possible applications. As for data
      transmission, the REFRESH and PREFETCH mechanisms were implemented to enhance
      data transfer efficiency. A total of 1107 consultations employing the
      telemedicine system were performed during the past 3 years. This technology was
      used most frequently for radiology consultation (32.7%, n = 362) and ultrasonic
      examination (19.5%, n = 216). An evaluation of the impact on diagnosis (507 valid
      cases) indicated that the diagnosis in 80 cases (15.78%) were altered on the
      basis of second opinions from a medical center; and the number of patients
      transferred to the medical center was reduced from 24 (4.7%) to eight cases. Most
      of the rural-site physicians (97%) thought that they did benefit from
      specialists' experience and knowledge via the telemedicine system. Based on 431
      valid questionnaires, the number of the patients with confidence in the
      telemedicine system at their local healthcare center increased from 72.6% to
      87.5%. Overall, more than 90% of patients and physicians believed that the system
      was valuable and provided satisfactory services.

PMID- 11311673
TI  - Sharing patient care records over the World Wide Web.
AB  - In order to obtain appropriate medical care, patients can be referred or
      transported from one hospital to another based on the capacity, capability and
      quality of medical care provided by hospitals. Therefore, enabling patient care
      records to be shared among hospitals is essential not only in delivering the
      quality of medical care services but also in saving medical expenses. Currently,
      most patient care records are paper-based and not well organized. Hence, they are
      usually incomplete and can hardly be accessed in time. The authors in this paper
      present methods to structure and represent patient care records, design
      mechanisms for interpreting and integrating the XML-based patient care records
      into the existing hospital information systems. More importantly, in our
      approach, each significant piece of medical record is associated with a tag based
      on the syntax and semantics of the XML. The XML-based medical records enable a
      computer to capture the meaning and structure of the document on the web. The
      authors have developed a unified referral information system in which patient
      care records can be shared among hospitals over the Internet. It can not only
      facilitate the referral process but also maintain the integrity of a patient's
      medical record from distributed hospitals. The workflow of the system basically
      follows the existing manual system and can easily be adapted. The working group
      on integration of municipal hospital information systems, Department of Health,
      Taipei City Government, has decided to adapt this system for referral practice
      among the municipal hospitals.

PMID- 11311674
TI  - Japanese experience of telemedicine in oncology.
AB  - We started telemedicine projects from 1990 with a telepathology system within
      Tsukiji Campus of National Cancer Center. In 1994, we connected Tsukiji Campus
      and Kashiwa Campus by 6 Mbps optical fiber leased line using IP protocol for data
      transmission, for teleconference, telepathology, and teleradiology projects. We
      also started connection of regional cancer centers and are now forming a cancer
      center network of 14 cancer centers. We are at present organizing 130
      teleconferences per year with an attendance of more than 16000 people as summary.
      We have also used a high-resolution image transferring system, such as SHD (2000
      pixelsx2000 pixels resolution) system on one side, and an economical telemedicine
      system using JAVA and a WWW browser (NCC_image) on the other side. We think that
      providing information is another field of telemedicine. We began the experimental
      gopher and WWW service in 1993. We are now providing official up-to-date cancer
      information for patients and healthcare professionals. We are getting more than
      400000 hits per month. We are also providing a teleconference video session which
      is held every week on the Internet using a Real Video system with synchronized
      slide presentation on the WWW browser. We are also organizing a Cancer Image
      Reference Database System including DICOM images with viewer software. This paper
      is a summary of the telemedicine projects performed at the National Cancer
      Center.

PMID- 11311675
TI  - Design of a PC-based multimedia telemedicine system for brain function
      teleconsultation.
AB  - During time-critical brain surgery, the detection of developing cerebral ischemia
      is particularly important because early therapeutic intervention may reduce the
      mortality of the patient. The purpose of this system is to provide an efficient
      means of remote teleconsultation for the early detection of ischemia,
      particularly when subspecialists are unavailable. The hardware and software
      design architecture for the multimedia brain function teleconsultation system
      including the dedicated brain function monitoring system is described. In order
      to comprehensively support remote teleconsultation, multi-media resources needed
      for ischemia interpretation were included: EEG signals, CSA, CD-CSA, radiological
      images, surgical microscope video images and video conferencing. PC-based system
      integration with standard interfaces and the operability over the Ethernet meet
      the cost-effectiveness while the modular software was customized with a diverse
      range of data manipulations and control functions necessary for shared workspace
      and standard interfaces.

PMID- 11311676
TI  - EMR based telegeriatric system.
AB  - INTRODUCTION: As medical services improve due to new technologies and
      breakthroughs, it has lead to an increasingly aging population. There has been
      much discussion and debate on how to solve various aspects such as psychological,
      socioeconomic and medical problems related to aging. Our effort is to implement a
      feasible telegeriatric medical service with the use of the state of the art
      technology to deliver medical services efficiently to remote sites where elderly
      homes are based. Telegeriatric system will lead to rapid decision-making in the
      presence of acute or subacute emergencies. This triage will also lead to a
      reduction of unnecessary admission. It will enable the doctors who visit these
      elderly homes on a once-a-week basis to improve their geriatric management skills
      by communication with geriatric specialist. Nursing skills in geriatric care will
      also benefit from this system. Integrated EMR service will be indispensable in
      the face of emergency admissions to hospitals. Evolution of EMR database would
      lead to future research in telegeriatrics and will help to identify the areas
      where telegeriatrics can be optimally used. METHODOLOGY: This system is based on
      current web browsing technology and broadband communication. EMR web based server
      is developed using Java Technology. EMR database was developed using Microsoft
      SQL server. Both are based at the Medical Informatics Programme, National
      University of Singapore. Two elderly homes situated in the periphery of Singapore
      and a leading government hospital in geriatric care has been chosen for the
      project. These three institutions and National University of Singapore are
      connected via ADSL protocol, which support high bandwidth, which is necessary for
      high quality videoconferencing. Each time a patient needs a teleconsultation, a
      nurse or doctor in the remote site sends the history to the EMR server. EMR
      server forwards the request to the Alexandra Hospital for consultation.
      Geriatrics specialists at Alexandra Hospital carry out teleward rounds twice
      weekly and on demand basis. SUMMARY OF RESULTS: Following the implementation of
      the system, a trial run has been done. This shows a high degree of coordination
      and cooperation between remote site and the Alexandra Hospital Also the patient
      compliance is very high and they prefer teleconsultation. CONCLUSION: Initial
      results show that telegeriatric system has definite advantages in managing
      geriatric patients at a remote site. As the system evolves, further research will
      show the areas where telegeriatrics can be used optimally.

PMID- 11311677
TI  - Wiring a medical school and teaching hospital for telemedicine.
AB  - The planning and installation of a telemedicine system for communication within a
      teaching hospital and its academic and hospital units with a capacity for
      accommodation of up to 400 video-stations is described. The system is intended
      for improving the communication between patients and health professionals, and
      between the health professionals themselves. It also provides the basis for
      improving pre-graduate teaching, especially problem-based learning, and all
      aspects of postgraduate teaching.

PMID- 11311678
TI  - Building a generic architecture for medical information exchange among healthcare
      providers.
AB  - Due to the inability to exchange clinical information among hospitals, continuity
      of care cannot be maintained and a tremendous amount of medical resource has been
      wasted. This paper describes an architecture that would facilitate exchange of
      clinical information among heterogeneous hospital information systems. It is
      dubbed 'Medical Information Exchange Center' or MIEC as part of a six-year Health
      Information Network Project hosted by the Department of Health. MIEC was designed
      so that it is innovative yet technically feasible today. It is convenient for
      authorized users yet secure enough so people can trust and has minimal impact to
      participated hospitals. Authorized users will be able to access information
      through two web-based interfaces directed to physician and non-physician users
      respectively. Hospitals are connected through a virtual private network to
      exchange patient information and users need to obtain a private key from the
      certificate authority in order to securely connect to MIEC. A pilot project was
      conducted to demonstrate the feasibility of this architecture and the problems
      encountered were discussed.

PMID- 11311679
TI  - Editor's corner.

PMID- 11311680
TI  - Hemochromatosis and iron therapy of Restless Legs Syndrome.

PMID- 11311681
TI  - Sleep electroencephalogram changes in acute hemispheric stroke.
AB  - Background/objective: Since reports of the effects of cerebral hemispheric stroke
      on sleep architecture are rare and contradictory, we prospectively studied 24
      patients with first acute supratentorial, extra-thalamic stroke.Methods: We
      assessed stroke severity, topography, and volume (on brain MRI). Sleep
      electroencephalogram recordings were performed a mean of 12 days after stroke
      onset, and scored for sleep stages over the healthy hemisphere. Sleep spindles
      and sawtooth waves were analyzed over both hemispheres. Data were compared with
      those of 17 age and gender-matched patients with normal brain imaging.Results:
      Compared to controls, stroke patients had lower total sleep time (P<0.01), lower
      sleep efficiency (P=0.02), and reduced amounts of NREM sleep stages 2-4 (P=0.02).
      Sleep spindles and sawtooth waves were often bilaterally reduced in patients with
      stroke volumes >25 ml. Abnormalities of REM sleep were more common in sleep
      studies performed within 3 days after stroke onset. Compared to patients with
      poor outcome, those with good outcome had higher sleep efficiency (P<0.01), more
      sleep time (P=0.02), and more NREM sleep stage 2 (P<0.01).Conclusion: Acute
      hemispheric stroke is accompanied by sleep EEG changes over the healthy
      hemisphere that correlate with stroke severity. These findings support the
      hypothesis that the cerebral hemispheres participate in the control of sleep.

PMID- 11311682
TI  - Determinants of compliance with nasal continuous positive airway pressure
      treatment applied in a community setting.
AB  - Objectives: To assess determinants of nasal continuous positive airway pressure
      (CPAP) compliance when applied in a community setting.Background: One-third of
      obstructive sleep apnea patients eventually refuse CPAP therapy. Treatment
      outcomes may be improved by identifying predictors of CPAP failure, including
      whether management by primary care physicians without sleep consultation affects
      results.Methods: Polysomnogram, chart review, and questionnaire results for
      regular CPAP users (n=123) were compared with those returning the CPAP machine
      (n=26).Results: Polysomnographic data and the presence of multiple sleep
      disorders were only modestly predictive of CPAP compliance. Striking differences
      in questionnaire responses separated CPAP users from non-users, who reported less
      satisfaction with all phases of their diagnosis and management. Rates of CPAP use
      were not significantly different between patients managed solely by their primary
      care physician or by a sleep consultant.Conclusions: Polysomnographic findings
      are unlikely to identify eventual CPAP non-compliers in a cost-effective fashion.
      Improvements in sleep apnea management may result from addressing the role of
      personality factors and multiple sleep disorders in determining compliance. In
      this practice setting, management by primary care physicians did not
      significantly degrade CPAP compliance.

PMID- 11311683
TI  - CPAP treatment does not affect glucose-insulin metabolism in sleep apneic
      patients.
AB  - Objective: We investigated glucose metabolism and insulin resistance in non-obese
      and moderately overweight sleep apnea patients, as well as their response to
      nasal CPAP treatment.Methods: A group of subjects with glucose intolerance was
      screened for sleep disordered breathing by clinical interview and ambulatory
      recordings. Ten subjects were found to have untreated sleep apnea and were asked
      to participate in further investigation. This included nocturnal polysomnography,
      oral glucose tolerance test and indirect calorimetry. Subjects then had
      calibration of nasal CPAP with polysomnography. Two months after start of
      treatment, all subjects were restudied as at baseline. In parallel, six
      obstructive sleep apnea syndrome (OSAS) subjects, diagnosed through the sleep
      clinic, were matched for gender, age and oxygen desaturation index with the other
      group, and had a euglycemic hyperinsulinemic clamp at baseline and after 2 months
      of nasal CPAP.Results: The first ten patients showed no change in total glucose
      oxidation, glucose oxidation by weight or by fat free mass, or insulin energetic
      expenditure, despite nocturnal usage of nasal CPAP. Similarly, when comparing
      baseline to the treatment at 2 months, the six OSAS patients had no change in
      mean glycemia, insulin, C peptide and hemoglobin (Hgb) A1C measurements. No
      difference in the amount of glucose infused during the duration of the clamp was
      noted either.Conclusion: Our data do not support the existence of a significant
      relationship between glucose and insulin metabolism and obstructive sleep apnea.
      Obesity, when present, is the important variable.

PMID- 11311684
TI  - Slow wave sleep rebound and REM rebound following the first night of treatment
      with CPAP for sleep apnea: correlation with subjective improvement in sleep
      quality.
AB  - Objective: The purpose of this study was to correlate changes in PSG parameters
      between the diagnostic polysomnogram (dPSG) and the first night of treatment with
      continuous positive airway pressure (CPAP) (cpapPSG) to subjective improvement in
      sleep quality.Background: In patients with obstructive sleep apnea syndrome
      (OSAS), therapy with CPAP results in reduction of sleep latency, stage 1 sleep,
      arousal index (Al) and respiratory disturbance index (RDI), and increase in stage
      2 sleep, REM sleep and REM density. No data exists on the differences in
      polysomnographic (PSG) parameters in patients who have subjective improvement in
      sleep quality and those who do not.Methods: We retrospectively reviewed PSG
      studies of 44 patients with OSAS who presented to the Sleep Disorders Center at
      Duke University Medical Center. Patient's qualitative assessment of sleep was
      noted using a Likert-type scale administered the morning after the dPSG and
      cpapPSG. PSG indices of patients noting subjective improvement were compared to
      those with no improvement.Results: Patients noting a subjective improvement in
      sleep quality showed a decrease in the percentages of stage 1 sleep (P<0.001) and
      an increase in percentages of stages 3 and 4 sleep (slow wave sleep rebound;
      P<0.007) and stage REM sleep (REM rebound; P<0.008).

PMID- 11311685
TI  - The age and other factors in the evaluation of compliance with nasal continuous
      positive airway pressure for obstructive sleep apnea syndrome. A Cox's
      proportional hazard analysis.
AB  - Objective: To elucidate the predictive role of age and other pre-treatment,
      putative confounding factors on compliance with nasal continuous positive airway
      pressure (nCPAP) therapy.Patients and methods: This study was designed as a
      prospective cohort study in the setting of a sleep laboratory in a teaching
      hospital at Saint Antoine, Paris. One hundred and sixty-three patients referred
      to the sleep laboratory with complaints of snoring and excessive daytime
      sleepiness for whom nCPAP had been prescribed for obstructive sleep apnea
      syndrome (OSAS; defined as an apnea-hypopnea index (AHI) of >15/h of sleep during
      a polysomnographic recording) were followed for a median period of 887 days. The
      main outcome measure was the risk ratio for elderly patients associated with
      nCPAP compliance.Results: Four patients, who remained under treatment, died
      before the end of the study, and 50 patients stopped their nCPAP therapy for
      reasons other than death (insomnia, equipment too noisy, etc.). When compliance
      curves were compared by univariate analysis (log-rank test), the oldest group
      (57/163 patients, >60 years old) was significantly less compliant with nCPAP than
      the youngest (P=0.01). However, in the Cox's proportional hazards model, age did
      not exert any independent effect on compliance with nCPAP after controlling for
      confounding factors (adjusted relative risk, 1.09, 0.5-2; P=0.70). On the other
      hand, female sex (adjusted relative risk, 2.8, 1.4-5.4; P=0.002), a body mass
      index (BMI) of </=30 kg/m(2) (adjusted relative risk, 2.2, 1.2-4; P=0.006), an
      Epworth sleepiness scale (ESS) score of </=15 (adjusted relative risk, 3.2, 1.1
      8.9; P=0.025), an AHI of </=30/h (adjusted relative risk, 2.2, 1.2-4; P=0.01) and
      a nCPAP of >/=12 cmH(2)O (adjusted relative risk, 2.3, 1.2-4.4; P=0.011) were
      predictive factors for non-compliance.Conclusion: This study suggests that there
      is no independent effect of age on compliance with nCPAP therapy.

PMID- 11311686
TI  - Sleep complaints in women of ages 40-64 years in relation to sleep in their
      parents.
AB  - Objective: To study the occurrence of sleep complaints in women in relation to
      such complaints in their parents.Background: Sleep complaints are common and may
      be affected by many somatic, mental, and life-style and environmental
      factors.Methods: A cross-sectional questionnaire survey was undertaken among 3669
      randomly selected women of ages 40-64 years. The women were asked about their own
      health and sleep and their recollection of the sleep of their parents.Results:
      The frequency of poor sleep was low among women reporting that neither parent had
      sleep disturbances. Sleep disturbances in the father, mother and both parents
      implied a 2.5 (95% confidence interval, 2.0-3.2), 2.5 (2.1-3.0) and 4.8-fold (3.4
      6.8) increase in sleep complaints in the investigated women, respectively. The
      frequencies of numerous awakenings, difficulty in falling asleep again and too
      little sleep increased similarly. A series of logistic regression analyses
      revealed that all sleep characteristics were evaluated more negatively in women
      who reported sleep disturbances in their parents and also reported themselves to
      be in poor health. All sleep variables deteriorated with age. Because data
      regarding parent sleep was based on subjects' recall of that sleep, the results
      should be interpreted with some caution.Conclusions: The frequency of sleep
      complaints in women aged from 40 to 64 years was increased if sleep disturbances
      were reported in their parents.

PMID- 11311687
TI  - Validation of the Johns Hopkins restless legs severity scale.
AB  - Determine reliability and validity of the Johns Hopkins restless legs severity
      scale (JHRLSS), an easily used clinical scale assessing severity of the restless
      legs syndrome (RLS). There is, prior to this study, no validated scale assessing
      the wide range of RLS severity. The JHRLSS has been used in prior studies to
      assess RLS severity, but has not previously been validated in relation to direct
      measures of the morbidity associated with RLS. A consecutive case series of 31
      RLS patients was used in the study. The JHRLSS was validated by its correlation
      with objective measures by a polysomnogram of the sleep disturbances associated
      with RLS (periodic leg movements of sleep per hour (PLMS/h), and sleep
      efficiency). Reliability was determined from the independent ratings of two
      clinicians. Reliability measures for the JHRLSS based on inter-rater agreement
      were 0.91 (Spearman Rho) and 0.87 (Cramers V). The subjective JHRLSS correlated
      significantly with both objective measures of sleep: sleep efficiency (R=0.60,
      P<0.01) and PLMS/h (R=0.45, P=0.01). The JHRLSS provides a reliable, valid,
      easily used clinical assessment of RLS severity.

PMID- 11311688
TI  - Sleepiness/alertness among healthy evening and morning type individuals.
AB  - Objective: The aim of this study was to determine the level of
      sleepiness/alertness among different chronotypes.Background: The Horne-Ostberg
      Morningness-Eveningness Questionnaire (MEQ) has allowed the characterization of
      chronotypes that are associated with a number of biological factors including:
      body temperature, cortisol rhythm, sleep patterns, and architecture.Methods:
      Fifty-six consecutive normal volunteers underwent an 8-h polysomnogram followed
      by a multiple sleep latency test (MSLT). Each subject also completed the MEQ and
      the Sleep/Wake Activity Inventory.Results: Evening types (ET) reported
      significantly later bedtimes and risetimes than both morning types (MT) and
      neither types (NT, P<0.05). On nocturnal polysomnography, the ET documented
      significantly longer latencies to stage 1 and persistent sleep when compared to
      both the NT and MT (P<0.01). There were no significant differences in the level
      of sleepiness on the MSLT across the different chronotypes. However, the pattern
      of sleepiness differed among them. While ET and NT showed differential sleep
      latencies across nap opportunities, MT showed no evidence of circadian variation
      on their level of sleepiness.Conclusions: There were no overall differences in
      daytime sleepiness/alertness across chronotypes. However, a differential pattern
      of sleep latencies was noted on the MSLT.

PMID- 11311689
TI  - Hemochromatosis and iron therapy of Restless Legs Syndrome.
AB  - Restless legs syndrome (RLS) occurs in some persons with iron deficiency, and
      some persons with RLS benefit from oral iron therapy. Approximately one in 200
      persons of northern European ancestry have hemochromatosis attributable to
      inheritance of two common mutations of the hemochromatosis-associated HFE gene on
      chromosome 6. We evaluated and treated a 46-year-old man with RLS who was
      diagnosed as having hemochromatosis after he developed new symptoms associated
      with taking iron therapy for RLS. He had transferrin saturation 88%, serum
      ferritin 658 ng/ml, and C282Y homozygosity. Therapeutic phlebotomy of one unit of
      blood (450-500 ml) weekly (total 24 units) relieved his non-RLS symptoms, caused
      RLS symptoms to occur more frequently, and was associated with transient fatigue
      and mild dependent edema. His sister, who also has RLS, was subsequently
      diagnosed as having hemochromatosis. We conclude that serum transferrin
      saturation and ferritin levels should be measured before initiation of iron
      therapy of RLS. Patients with a history of iron deficiency or low serum iron
      parameters should undergo evaluation for iron deficiency; patients who have
      histories suggestive of hemochromatosis or iron overload or elevated pre
      treatment transferrin saturation or serum ferritin levels should undergo
      evaluation to determine the cause of these abnormalities before they are treated
      with iron. In all persons with RLS treated with oral iron, serum iron parameters
      should be re-measured once or twice yearly during therapy.

PMID- 11311690
TI  - Journal search and commentary.

PMID- 11311691
TI  - Article reviewed: Rapid eye movement sleep behaviour disorder: demographic,
      clinical and laboratory findings in 93 cases.

PMID- 11311692
TI  - Article reviewed: Papilledema and obstructive sleep apnea syndrome.

PMID- 11311693
TI  - Article reviewed: Daytime sleepiness and EEG spectral analysis in apneic patients
      before and after treatment with continuous positive airway pressure.

PMID- 11311694
TI  - Article reviewed: Impairment of endothelium-dependent vasodilation of resistance
      vessels in patients with obstructive sleep apnea.

PMID- 11311695
TI  - Web Watch.

PMID- 11311696
TI  - Web Watch.

PMID- 11311697
TI  - Dependence of yield strain of human trabecular bone on anatomic site.
AB  - Understanding the dependence of human trabecular bone strength behavior on
      anatomic site provides insight into structure-function relationships and is
      essential to the increased success of site-specific finite element models of
      whole bones. To investigate the hypothesis that the yield strains of human
      trabecular bone depend on anatomic site, the uniaxial tensile and compressive
      yield properties were compared for cylindrical specimens from the vertebra
      (n=61), proximal tibia (n=31), femoral greater trochanter (n=23), and femoral
      neck (n=27) taken from 61 donors (67+/-15years). Test protocols were used that
      minimized end artifacts and loaded specimens along the main trabecular
      orientation. Yield strains by site (mean+/-S.D.) ranged from 0.70+/-0.05% for the
      trochanter to 0.85+/-0.10% for the femoral neck in compression, from 0.61+/-0.05%
      for the trochanter to 0.70+/-0.05% for the vertebra in tension, and were always
      higher in compression than tension (p<0.001). The compressive yield strain was
      higher for the femoral neck than for all other sites (p<0.001), as was the
      tensile yield strain for the vertebra (p<0.007). Analysis of covariance, with
      apparent density as the covariate, indicated that inter-site differences existed
      in yield stress even after adjusting statistically for density (p<0.035).
      Coefficients of variation in yield strain within each site ranged from only 5
      12%, consistent with the strong linear correlations (r(2)=0.94-0.98) found
      between yield stress and modulus. These results establish that the yield strains
      of human trabecular bone can differ across sites, but that yield strain may be
      considered uniform within a given site despite substantial variation in elastic
      modulus and yield stress.

PMID- 11311698
TI  - Correlation of thoracic and lumbar vertebral failure loads with in situ vs. ex
      situ dual energy X-ray absorptiometry.
AB  - In this study we explore the hypothesis that estimates of failure loads in the
      thoracic spine by lumbar dual energy X-ray absorptiometry (DXA) are compromised
      of skeletal heterogeneity throughout the spine and artifacts of spinal DXA. We
      studied the correlation between mechanical failure loads of thoracic and lumbar
      vertebrae, and that of in situ vs. ex situ lumbar DXA with thoracic and lumbar
      fracture loads, respectively. One hundred and nineteen subjects (76 female, age
      82+/-9yr; 43 male, age 77+/-11yr) were examined under in situ conditions
      (anterior-posterior direction), the scans being repeated ex situ (lateral
      projection) in 68 cases. The failure loads of thoracic vertebrae (T) 6 and 10,
      and lumbar vertebra (L) 3 were determined in axial compression, using a
      functional 3-segment unit. The correlation between thoracic failure loads (T6 vs.
      T10) was significantly (p<0.01) higher (r=0.85) than those between thoracic and
      lumbar vertebrae (r=0.68 and 0.61, respectively). Lateral ex situ DXA displayed a
      significantly higher correlation (p<0.05) with lumbar vertebral fracture loads
      than in situ anterior-posterior DXA (r=0.85 vs. 0.71), but the correlation of
      thoracic failure loads with lateral ex situ lumbar DXA was similar to that
      obtained in situ in anterior-posterior direction (r=0.69 vs. 0.69 for T10, and
      r=0.61 vs. 0.65 for T6). The correlation between fracture loads of different
      spinal segments, and between DXA and failure loads was not significantly
      different between men and women. The results demonstrate a substantial
      heterogeneity of mechanical competence throughout the spine in elderly
      individuals. Because of the high incidence of fractures in the thoracic spine,
      these findings suggest that, clinically, lateral DXA involves no relevant
      advantage over anterior-posterior measurements of the lumbar spine.

PMID- 11311699
TI  - The threshold trip duration for which recovery is no longer possible is
      associated with strength and reaction time.
AB  - The recovery of young adults from trips of increasing severity was studied. Our
      null hypothesis was that lower extremity strength, and reaction time, step time,
      step distance and step velocity measured in a volitional stepping task would not
      explain a significant portion of the variance in the magnitude of the threshold
      trip duration for which recovery is no longer possible. Ten males and 11 females
      (average age 26.8 and 28.4 years old, respectively) were subjected to trips of
      increasing duration until recovery was no longer possible with a single step. The
      average threshold trip duration for which subjects were no longer able to recover
      with a single step was 681+/-169ms. The threshold trip duration significantly
      increased as lower extremity strength increased and volitional reaction time
      decreased (multiple stepwise linear regression: R(2)=0.52, p=0.001). The other
      volitional step parameters and the subject characteristics were not significantly
      associated with the magnitude of the threshold trip duration. These results
      suggest that some trip-related falls may be due to slower reaction times and/or
      reduced lower extremity strengths.

PMID- 11311700
TI  - A dynamic model of the forearm including fatigue.
AB  - A biomechanical model of the forearm, consisting of 61 muscle-tendon systems or
      tendons and 8 sections, is presented. The model can be used to calculate the
      muscle forces when resultant of the external forces and the motion is known.
      Calculations are based on constraints of muscle forces, joint forces, contact
      forces, and tendon junctions, and a load sharing principle telling which of the
      feasible solutions are likely and which are not. Fatigue is accounted for by
      updating the upper limits of the muscle forces according to the loading history.
      As an example, the model is used to predict the load sharing between the fingers
      when they are pressed against a table with a given total force.

PMID- 11311701
TI  - On the potentially protective role of contact constraints on saccular aneurysms.
AB  - Most intracranial saccular aneurysms remain asymptomatic until rupture. Yet, some
      unruptured lesions present with various symptoms, often related to the
      compression of a nerve or other intracranial tissue. An obvious question,
      therefore, is whether or not symptomatic unruptured lesions necessarily have a
      greater rupture-potential than asymptomatic ones. In this paper, we show
      numerically that contact constraints can have a protective effect on certain
      lesions. Specifically, finite element analyses of stress fields in model
      axisymmetric lesions, with and without the presence of a rigid contacting
      obstacle at the fundus, reveal that with the exception of near point loads, the
      constraint decreases the stresses near the fundus. Given that it is well accepted
      that rupture occurs when wall stress exceeds wall strength, these findings
      suggest that the rupture-potential will be lower in at least one sub-class of
      constrained versus comparable unconstrained lesions. Because of the myriad of
      sizes, shapes, and compositions of saccular aneurysms, however, there is a need
      to examine this important issue further, hopefully based on an increased
      awareness for clinical data on lesion-tissue interactions.

PMID- 11311702
TI  - The influence of the leaflets' curvature on the flow field in two bileaflet
      prosthetic heart valves.
AB  - A successful mechanical prosthetic heart valve design is the bileaflet valve,
      which has been implanted for the first time more than 20 years ago. A key feature
      of bileaflet valves is the geometry of the two leaflets, which can be very
      important in determining the flow field. Laser Doppler anemometry (LDA) was used
      to perform an accurate study of the velocity and turbulence shear stress peak
      values (TSS(max)) fields at four distances from the valve plane. TSS(max) is a
      relevant parameter to assess the risk of hemolysis and platelet activation
      associated to the implantation of a prosthetic device, continuously interacting
      with blood. Two bileaflet valves were tested: the St. Jude HP and the Sorin
      Bicarbon, of the same nominal size (19mm). The former has flat leaflets, whereas
      the latter's leaflets have a cylindrical surface. A high regime (CO: 6l/min) was
      imposed, in order to test the two valves at maximum Reynolds number and
      consequent turbulence generation. The flat-leaflet design of the St. Jude
      generates a TSS field constant with distance; on the contrary, the Bicarbon's
      shear stress field undergoes an evident development, with an unexpected central
      peak at a distance comparable to the valve's dimensions (21mm). The two bileaflet
      valves tested, although very similar in design, behave very differently as for
      their turbulence properties. In particular, the concept of curved wake leads to
      conclude that the curvature of the leaflets' surface must be identified as an
      important parameter, which deserves careful attention in PHV design and
      development.

PMID- 11311703
TI  - "In vivo" determination of hip joint separation and the forces generated due to
      impact loading conditions.
AB  - Numerous supporting structures assist in the retention of the femoral head within
      the acetabulum of the normal hip joint including the capsule, labrum, and
      ligament of the femoral head (LHF). During total hip arthroplasty (THA), the LHF
      is often disrupted or degenerative and is surgically removed. In addition, a
      portion of the remaining supporting structures is transected or resected to
      facilitate surgical exposure. The present study analyzes the effects of LHF
      absence and surgical dissection in THA patients. Twenty subjects (5 normal hip
      joints, 10 nonconstrained THA, and 5 constrained THA) were evaluated using
      fluoroscopy while performing active hip abduction. All THA subjects were
      considered clinically successful. Fluoroscopic videos of the normal hips were
      analyzed using digitization, while those with THA were assessed using a
      computerized interactive model-fitting technique. The distance between the
      femoral head and acetabulum was measured to determine if femoral head separation
      occurred. Error analysis revealed measurements to be accurate within 0.75mm. No
      separation was observed in normal hips or those subjects implanted with
      constrained THA, while all 10 (100%) with unconstrained THA demonstrated femoral
      head separation, averaging 3.3mm (range 1.9-5.2mm). This study has shown that
      separation of the prosthetic femoral head from the acetabular component can
      occur. The normal hip joint has surrounding capsuloligamentous structures and a
      ligament attaching the femoral head to the acetabulum. We hypothesize that these
      soft tissue supports create a passive, resistant force at the hip, preventing
      femoral head separation. The absence of these supporting structures after THA may
      allow increased hip joint forces, which may play a role in premature polyethylene
      wear or prosthetic loosening.

PMID- 11311704
TI  - Spatial interaction between tissue pressure and skeletal muscle perfusion during
      contraction.
AB  - The vascular waterfall theory attributes decreased muscle perfusion during
      contraction to increased intramuscular pressure (P(IM)) and concomitant increase
      in venous resistance. Although P(IM) is distributed during contractions, this
      theory does not account for heterogeneity. This study hypothesises that pressure
      heterogeneity could affect the interaction between P(IM) rise and perfusion.
      Regional tissue perfusion during submaximum (100kPa) tetanic contraction is
      studied, using a finite element model of perfused contracting skeletal muscle.
      Capillary flow in muscles with one proximal artery and vein (SIM(1)) and with an
      additional distal artery and vein (SIM(2)) is compared. Blood flow and pressures
      at rest and P(IM) during contraction ( approximately 25kPa maximally) are similar
      between simulations, but capillary flow and venous pressure differ. In SIM(2),
      venous pressure and capillary flow correspond to P(IM) distribution, whereas
      capillary flow in SIM(1) is less than 10% of flow in SIM(2), in the muscle half
      without draining vein. This difference is caused by a high central P(IM),
      followed by central venous pressure rise, in agreement with the waterfall theory.
      The high central pressure (SIM(1)), obstructs outflow from the distal veins.
      Distal venous pressure rises until central blood pressure is reached, although
      local P(IM) is low. Adding a distal vein (SIM(2)) restores the perfusion. It is
      concluded that regional effects contribute to the interaction between P(IM) and
      perfusion during contraction. Unlike stated by the vascular waterfall theory,
      venous pressure may locally exceed P(IM). Although this can be explained by the
      principles of this theory, the theory does not include this phenomenon as such.

PMID- 11311705
TI  - Mechanical boundary conditions of fracture healing: borderline indications in the
      treatment of unreamed tibial nailing.
AB  - Unreamed nailing favors biology at the expense of the achievable mechanical
      stability. It is therefore of interest to define the limits of the clinical
      indications for this method. The extended usage of unreamed tibial nailing
      resulted in reports of an increased rate of complications, especially for the
      distal portion of the tibia. The goals of this work were to gain a thorough
      understanding of the load-sharing mechanism between unreamed nail and bone in a
      fractured tibia, to identify the mechanical reasons for the unfavorable clinical
      results, and to identify borderline indications due to biomechanical factors. In
      a three-dimensional finite element model of a human tibia, horizontal defects
      were stabilized by means of unreamed nailing for five different fracture
      locations, including proximal and distal borderline indications for this
      treatment method. The loading of the bone, the loading of the implant and the
      inter-fragmentary strains were computed. The findings of this study show that
      with all muscle and joint contact forces included, nailing leads to considerable
      unloading of the interlocked bone segments. Unreamed nailing of the distal defect
      results in an extremely low axial and high shear strain between the fragments.
      The results suggest that mechanical conditions are advantageous to unreamed
      nailing of proximal and mid-diaphyseal defects. Apart from biological reasons,
      clinical problems reported for distal fractures may be due to the less favorable
      mechanical conditions in unreamed nailing. From a biomechanical perspective, the
      treatment of distal tibial shaft fractures by means of unreamed nailing without
      additional fragment contact or without stabilizing the fibula should be carefully
      reconsidered.

PMID- 11311706
TI  - How to test very soft biological tissues in extension?
AB  - Mechanical properties of very soft tissues, such as brain, liver and kidney,
      until recently have largely escaped the attention of researchers because these
      tissues do not bear mechanical loads. However, developments in Computer
      Integrated and Robot-Aided Surgery - in particular, the emergence of automatic
      surgical tools and robots - as well as advances in Virtual Reality techniques,
      require closer examination of the mechanical properties of very soft tissues and,
      ultimately, the construction of corresponding, realistic mathematical models. A
      body of knowledge about mechanical properties of very soft tissues, assembled in
      recent years, has been almost exclusively based on the results of compression,
      indentation and impact tests. There are no results of tensile tests available.
      This state of affairs, in the author's opinion, is caused by the lack of
      analytical solution relating a measured quantity - machine head displacement - to
      strain in simple extension experiments of cylindrical samples with low aspect
      ratio. In the paper this important solution is presented. The theoretical
      solution obtained is valid for isotropic, incompressible materials for moderate
      deformations (<30%) when it can be assumed that planes initially perpendicular to
      the direction of applied extension remain plane. Two astonishing results are
      obtained: (i) deformed shape of a cylindrical sample subjected to uniaxial
      extension is independent on the form of constitutive law, (ii) vertical extension
      in the plane of symmetry lambda(z) is proportional to the total change of height
      for strains as large as 30%. The importance and relevance of these results to
      testing procedures in Biomechanics is highlighted.

PMID- 11311707
TI  - Effects of curved inlet tubes on air flow and particle deposition in bifurcating
      lung models.
AB  - In vivo bifurcating airways are complex and the airway segments leading to the
      bifurcations are not always straight, but curved to various degrees. How do such
      curved inlet tubes influence the motion as well as local deposition and hence the
      biological responses of inhaled particulate matter in lung airways? In this paper
      steady laminar dilute suspension flows of micron-particles are simulated in
      realistic double bifurcations with curved inlet tubes, i.e., 0 degrees < or
      =theta< or =90 degrees, using a commercial finite-volume code with user-enhanced
      programs. The resulting air-flow patterns as well as particle transport and wall
      depositions were analyzed for different flow inlet conditions, i.e., uniform and
      parabolic velocity profiles, and geometric configurations. The curved inlet
      segments have quite pronounced effects on air-flow, particle motion and wall
      deposition in the downstream bifurcating airways. In contrast to straight double
      bifurcations, those with bent parent tubes also exhibit irregular variations in
      particle deposition efficiencies as a function of Stokes number and Reynolds
      number. There are fewer particles deposited at mildly curved inlet segments, but
      the particle deposition efficiencies at the downstream sequential bifurcations
      vary much when compared to those with straight inlets. Under certain flow
      conditions in sharply curved lung airways, relatively high, localized particle
      depositions may take place. The findings provide necessary information for
      toxicologic or therapeutic impact assessments and for global lung dosimetry
      models of inhaled particulate matter.

PMID- 11311708
TI  - The production of nitric oxide and prostaglandin E(2) by primary bone cells is
      shear stress dependent.
AB  - Loading-induced flow of interstitial fluid through the lacuno-canalicular network
      is a likely signal for bone cell adaptive responses. However, the nature of the
      stimulus that activates the cell is debated. Candidate stimuli include wall shear
      stress, streaming potentials, and chemotransport. We have addressed the nature of
      the flow-derived cell stimulus by comparing variations in fluid transport with
      variations in wall shear stress, using nitric oxide (NO) and prostaglandin E(2)
      (PGE(2)) production as a parameter of bone cell activation. Adult mouse long bone
      cell cultures were treated for 15min with or without pulsating fluid flow using
      the following regimes: Low PFF, mean flow rate 0.20 cm(3)/s, 3 Hz, shear stress
      0.4+/-0.12 Pa; Medium PFF, 0.33 cm(3)/s, 5 Hz, 0.6+/-0.27 Pa; and High PFF, 0.63
      cm(3)/s, 9Hz, 1.2+/-0.37 Pa. In some Low PFF experiments, 2.8% neutral dextran
      (mol. wt. 4.98x10(4)) was added to the flow medium to increase the viscosity,
      thereby increasing the wall shear stress 3-fold to a level similar of the High
      PFF stimulus, but without affecting streaming potentials or chemotransport. NO
      and PGE(2) production were stimulated by Low, Medium, and High PFF in a dose
      dependent manner. Application of Low PFF using dextran-supplemented medium,
      enhanced both the NO and PGE(2) response by 3-fold, to a level mimicking the
      response to High PFF at normal viscosity. These results show that the production
      of NO and PGE(2) by bone cells can be enhanced in a dose-dependent manner by
      fluid flow of increasing wall shear stress. Therefore, the stimulus leading to NO
      and PGE(2) production is the flow-derived shear stress, and not streaming
      potentials or chemotransport.

PMID- 11311709
TI  - Applied horizontal force increases impact loading in reduced-gravity running.
AB  - The chronic exposure of astronauts to microgravity results in structural
      degradation of their lower limb bones. Currently, no effective exercise
      countermeasure exists. On Earth, the impact loading that occurs with regular
      locomotion is associated with the maintenance of bone's structural integrity, but
      impact loads are rarely experienced in space. Accurately mimicking Earth-like
      impact loads in a reduced-gravity environment should help to reduce the
      degradation of bone caused by weightlessness. We previously showed that running
      with externally applied horizontal forces (AHF) in the anterior direction
      qualitatively simulates the high-impact loading associated with downhill running
      on Earth. We hypothesized that running with AHF at simulated reduced gravity
      would produce impact loads equal to or greater than values experienced during
      normal running at Earth gravity. With an AHF of 20% of gravity-specific body
      weight at all gravity levels, impact force peaks increased 74%, average impact
      loading rates increased 46%, and maximum impact loading rates increased 89%
      compared to running without any AHF. In contrast, AHF did not substantially
      affect active force peaks. Duty factor and stride frequency decreased modestly
      with AHF at all gravity levels. We found that running with an AHF in simulated
      reduced gravity produced impact loads equal to or greater than those experienced
      at Earth gravity. An appropriate AHF could easily augment existing partial
      gravity treadmill running exercise countermeasures used during spaceflight and
      help prevent musculoskeletal degradation.

PMID- 11311710
TI  - Mechanisms of female urinary continence under stress: frequency spectrum
      analysis.
AB  - Intravesical and urethral pressure signals during cough and Valsalva maneuvers
      for 15 continent women were analyzed with frequency spectrum analysis. Clear
      modulation of the urethral pressure changes by the intravesical pressure rise
      during stress maneuvers was demonstrated in the frequency bands of 14 and 7 Hz
      for cough and Valsalva, respectively. The linearity between the urethral and
      intravesical pressure signals was strong for cough, but relatively weaker for
      Valsalva. The observed linearity lead to the formulation of a modified continence
      equation to mathematically quantify stress leak point pressure (sLPP):
      sLPP=MUCP/(1-alpha1)+RBP. This algebraic equation demonstrated that sLPP depends
      on pressure transmission, resting bladder pressure, and maximum urethral closure
      pressure. The equation was validated with excellent theoretical predictions for
      the 15 continent subjects (R(2)=0.98 and 0.97 for cough and Valsalva leak point
      pressure, respectively) and good but somewhat weaker predictions for 46 stress
      incontinent women (R(2)=0.79 and 0.48, respectively). It has been shown that
      pressure transmission plays the most important role in female continence
      function, while it may be attributable to passive structural origin as evidenced
      by the minimal time delay between the two pressure signals, in the order of a few
      milliseconds. It can be concluded that coughing seems to have a more mechanical,
      rather than neuromuscular basis for its signal dynamics. This study suggests that
      a complete assessment of female stress continence function requires comprehensive
      urodynamic information in terms of pressure transmission, maximum urethral
      closure pressure, and resting bladder pressure.

PMID- 11311711
TI  - In vitro modeling of human tibial strains during exercise in micro-gravity.
AB  - Prolonged exposure to micro-gravity causes substantial bone loss (Leblanc et al.,
      Journal of Bone Mineral Research 11 (1996) S323) and treadmill exercise under
      gravity replacement loads (GRLs) has been advocated as a countermeasure. To date,
      the magnitudes of GRLs employed for locomotion in space have been substantially
      less than the loads imposed in the earthbound 1G environment, which may account
      for the poor performance of locomotion as an intervention. The success of future
      treadmill interventions will likely require GRLs of greater magnitude. It is
      widely held that mechanical tissue strain is an important intermediary signal in
      the transduction pathway linking the external loading environment to bone
      maintenance and functional adaptation; yet, to our knowledge, no data exist
      linking alterations in external skeletal loading to alterations in bone strain.
      In this preliminary study, we used unique cadaver simulations of micro-gravity
      locomotion to determine relationships between localized tibial bone strains and
      external loading as a means to better predict the efficacy of future exercise
      interventions proposed for bone maintenance on orbit. Bone strain magnitudes in
      the distal tibia were found to be linearly related to ground reaction force
      magnitude (R(2)>0.7). Strain distributions indicated that the primary mode of
      tibial loading was in bending, with little variation in the neutral axis over the
      stance phase of gait. The greatest strains, as well as the greatest strain
      sensitivity to altered external loading, occurred within the anterior crest and
      posterior aspect of the tibia, the sites furthest removed from the neutral axis
      of bending. We established a technique for estimating local strain magnitudes
      from external loads, and equations for predicting strain during simulated micro
      gravity walking are presented.

PMID- 11311712
TI  - Sensitivity of damage predictions to tissue level yield properties and apparent
      loading conditions.
AB  - High-resolution finite element models of trabecular bone failure could be used to
      augment current techniques for measuring damage in trabecular bone. However, the
      sensitivity of such models to the assumed tissue yield properties and apparent
      loading conditions is unknown. The goal of this study was to assess the
      sensitivity of the amount and mode (tension vs. compression) of tissue level
      yielding in trabecular bone to these factors. Linear elastic, high-resolution
      finite element models of nine bovine tibial trabecular bone specimens were used
      to calculate the fraction of the total tissue volume that exceeded each criterion
      for apparent level loading to the reported elastic limit in both on-axis and
      transverse compression and tension, and in shear. Four candidate yield criteria
      were studied, based on values suggested in the literature. Both the amount and
      the failure mode of yielded tissue were sensitive to the magnitudes of the tissue
      yield strains, the degree of tension-compression asymmetry of the yield
      criterion, and the applied apparent loads. The amount of yielded tissue was most
      sensitive to the orientation of the applied apparent loading, with the most
      tissue yielding for loading along the principal trabecular orientation and the
      least for loading perpendicular to it, regardless of the assumed tissue level
      yield criterion. Small changes in the magnitudes and the degree of asymmetry of
      the tissue yield criterion resulted in much larger changes in the amount of
      yielded tissue in the model. The results indicate that damage predictions based
      on high-resolution finite element models are highly sensitive to the assumed
      tissue yield properties. As such, good estimates of these values are needed
      before high-resolution finite element models can be applied to the study of
      trabecular bone damage. Regardless of the assumed tissue yield properties, the
      amount and type of damage that occurs in trabecular bone depends on the relative
      orientations of the applied apparent loads to the trabecular architecture, and
      this parameter should be controlled for both experimental and computational
      damage studies.

PMID- 11311713
TI  - Self-organisation and orderly processes by individual protein complexes in the
      bacterial cell.
AB  - In the bacterial cell, individual multimeric proteins and multiprotein assemblies
      perform and control orderly processes. Individual motor enzyme complexes
      accomplish highly complex functions, such as nucleic acid and protein syntheses,
      with impressive efficiency and fidelity. Lac operon repression by the lac
      repressor is effectively controlled via a single molecular switch. There are only
      few copies of, for example, DNA polymerase holoenzyme and lac repressor and few
      specific target molecules/sites, with which these protein complexes interact,
      present in a single E. coli cell. These interactive processes take place in
      submicron-sized spaces characterised by extreme crowding (volume exclusion) of
      macromolecules and small molecules, heterogeneity and non-ideality. Recent
      evidence reinforces the fundamental difference of the cytoplasmic as compared
      with in vitro ("test tube") reaction conditions. This is reflected in the
      breakdown of the applicability of "bulk phase" thermodynamic, macroscopic
      chemical kinetic and diffusion laws to interactions of individual macromolecules
      and target sites in a single cell. Stochastic kinetic models and stochastic
      simulations enable the statistical description and analysis of biochemical
      reactions and binding processes which involve small numbers of reactants. New
      unifying concepts and models are required for the quantitative understanding of
      the microscopic self-organisation of multi-protein complexes and the dynamic
      order at the single-protein assembly and single-switch level in the living cell.

PMID- 11311714
TI  - Polarity and form regulation in development and reconstitution.
AB  - In the literature, it is often assumed, for example with respect to Hydra, that
      several Turing systems coexist and it is also assumed that maintaining the polar
      profile, even when the system increases in size, is important for the polarity of
      the final phenotype. It is shown here that in reality there is only one Turing
      system, Child's system. To obtain a complete polar individual or organ, whether
      in reconstitution or development, it is essential that the complete succession of
      metabolic patterns occurs. Child's concepts of physiological dominance,
      subordination and isolation are interpreted in the light of Turing theory and in
      particular the Turing wavelength. It is emphasised, particularly by pointing to
      Child's metabolic patterns in coelenterates, both in development and in
      reconstitution, that it is the elongation that drives the succession polar
      metabolic pattern-->bipolar metabolic pattern, and this corresponds to the
      prediction of Turing theory supporting the thesis that Child's metabolic pattern
      is a Turing pattern. It is shown that if we assume that ATP is the Turing
      inhibitor then the many results of Child about the reduction of the scale of
      organisation with the decrease in the intensity of the energy metabolism
      correspond to the reduction of the Turing wavelength. The interplay between the
      Turing wavelength and the length of the form explains the conditions of
      reconstitution under which partial forms, wholes and form regulation are
      obtained. It is suggested that higher metabolism is responsible for both larger
      size and larger Turing wavelength thus securing form regulation. The results
      could be of importance in modern 'regenerative biology'. Heteromorphosis, i.e.
      animals with two heads (or two tails), one at each end, is explained by a bipolar
      Turing-Child metabolic pattern replacing a polar metabolic pattern. This can be
      brought about by chemical or by genetic means and indeed the prediction for
      Drosophila that the transition, wild type-->Bicaudal D, occurs because a polar
      Turing pattern is replaced by bipolar Turing pattern is confirmed, again if we
      accept that Child's metabolic pattern is the underlying Turing pattern. Child's
      experiments on Drosophila, including the requirement of critical length for
      metabolic polarity, are explained by Turing theory. Phenocopies and phenotypes
      are explained by the Turing-Child theory. It is shown that both Child's results
      about metabolic patterns and modern results for Hydra about gap junctions,
      'endogeneous inhibitor' and gene expression, are correlated and explained by
      (cAMP, ATP) Turing theory. It is argued that the double-gradient hypothesis is
      incorrect in its original formulation and that it is Child's conception of
      succeeding metabolic patterns that is the correct one and that it corresponds to
      the prediction of the Turing theory.

PMID- 11311715
TI  - The emergence of life on Earth.
AB  - Combined top-down and bottom-up research strategies and the principle of
      biological continuity were employed in an attempt to reconstruct a comprehensive
      origin of life theory, which is an extension of the coevolution theory (Lahav and
      Nir, Origins of Life Evol. Biosphere (1997) 27, 377-395). The resulting theory of
      emergence of templated-information and functionality (ETIF) addresses the
      emergence of living entities from inanimate matter, and that of the central
      mechanisms of their further evolution. It proposes the emergence of short organic
      catalysts (peptides and proto-ribozymes) and feedback-loop systems, plus their
      template-and-sequence-directed (TSD) reactions, encompassing catalyzed
      replication and translation of populations of molecules organized as chemical
      informational feedback loop entities, in a fluctuating (wetting-drying)
      environment, functioning as simplified extant molecular-biological systems. The
      feedback loops with their TSD systems are chemically and functionally continuous
      with extant living organisms and their emergence in an inanimate environment may
      be defined as the beginning of life. The ETIF theory considers the emergence of
      bio-homochirality, a primordial genetic code, information and the incorporation
      of primordial metabolic cycles and compartmentation into the emerging living
      entities. This theory helps to establish a novel measure of biological
      information, which focuses on its physical effects rather than on the structure
      of the message, and makes it possible to estimate the time needed for the
      transition from the inanimate state to the closure of the first feedback-loop
      systems. Moreover, it forms the basis for novel laboratory experiments and
      computer modeling, encompassing catalytic activity of short peptides and proto
      RNAs and the emergence of bio-homochirality and feedback-loop systems.

PMID- 11311716
TI  - Susceptibility to trypsinolysis of esterified milk proteins.
AB  - Methyl-, ethyl- and propyl-esters of beta-lactoglobulin, alpha-lactalbumin and
      beta-casein were prepared and then hydrolyzed with trypsin in various conditions.
      Resulting hydrolysates were analysed by SDS electrophoresis and RP-HPLC. The
      degree of hydrolysis of esterified samples was generally lower than those of the
      non-modified proteins. The highest degrees of hydrolysis were obtained at pH 7--8
      with native and esterified protein samples. beta-Lactoglobulin propyl ester and
      beta-casein methyl ester yielded the lowest degrees of hydrolysis. Ethyl- and
      propyl-esters of beta-casein showed high resistance towards tryptic attack, even
      after 20 h of hydrolysis. SDS electrophoretic patterns of tryptic hydrolysates of
      native proteins showed bands corresponding to low molecular weights. Tryptic
      hydrolysates of esterified proteins showed bands with higher sizes. RP-HPLC
      profiles of tryptic hydrolysates of esterified samples showed peaks with longer
      elution times than those obtained with native proteins, indicating the presence
      of more hydrophobic peptide populations. A peptic pre-treatment improved tryptic
      action on esterified proteins. It resulted in a better resolution of RP-HPLC
      profiles and in a complete disappearance of the protein after 20 h tryptic
      hydrolysis.

PMID- 11311717
TI  - Solution conformation of an RNA--DNA hybrid duplex containing a pyrimidine RNA
      strand and a purine DNA strand.
AB  - RNA--DNA hybrid duplexes are involved in transcription, replication and reverse
      transcription of nucleic acids. Information on such duplexes may shed some light
      on the mechanism of these processes. For this purpose, the influence of base
      composition on the structure of a polypyrimidine--polypurine RNA--DNA duplex
      r(cucuccuucucuu). d(GAGAGGAAGAGAA) has been studied using 1H, 31P and 13C NMR
      experiments, molecular modeling (JUMNA program) and NOE back-calculation methods.
      The resulting structure of the 13-mer hybrid duplex shows that the RNA strand is
      in the expected A-type conformation while the DNA strand is in a very flexible
      conformation. In the DNA strand, the desoxyribose sugars retain the C2'-endo B
      type conformation. The duplex helical parameters (such as inclination, twist and
      displacement of the bases) are close to the A-type conformation. No bending was
      observed for the global axis curvature. The major groove width is close to the B
      form value and the minor groove width is intermediate between standard values for
      A and B-forms. These results are in favour of the independence of minor groove
      size (where RNase H interacts) and the base composition of the hybrid duplexes.

PMID- 11311718
TI  - Primary structure deduction and molecular modelling from a cDNA of a
      cellobiohydrolase-like protein from the white-rot fungus Coriolus versicolor.
AB  - Molecular cloning and cDNA sequencing analysis were used to elucidate the primary
      structure of a cellulase-like structure from the white-rot fungus Coriolus
      versicolor. The cDNA of interest was isolated from a cDNA library obtained from
      C. versicolor mycelia grown on cellulase inducer medium. A pattern search showed
      that this cellulase belongs to the glycosyl hydrolases family 6. From the deduced
      amino acid sequence, models of the binding and catalytic domains were built by
      homology modelling. The constructed models present a typical cellulose-binding
      domain at the N-terminal region, a rich Pro, Ser, Thr linker peptide, and a
      catalytic domain at the C-terminus region.

PMID- 11311719
TI  - Comparative studies of skeletal soluble matrices from some Scleractinian corals
      and Molluscs.
AB  - The soluble organic matrices extracted from aragonitic skeletons of five
      Scleractinia and two Molluscs were analyzed using FTIR spectrometry, HPLC and 2-D
      gel electrophoresis. All these methods show that scleractinian and molluscan
      matrices are different. Both matrices are acidic with poorly separated molecular
      weights. The scleractinian matrices are highly glycosylated, whereas the
      molluscan matrices are not as shown by stains in 2D-electrophoresis. These
      results were in accordance with earlier data: high S contents in Scleractinia
      skeletons and low S contents in Mollusca shells. These results confirm the
      control of the morphology and the chemical composition of aragonite biocrystals
      in various taxa.

PMID- 11311720
TI  - Myo-inositol hexasulphate and low molecular weight heparin binding to human
      acidic fibroblast growth factor: a calorimetric and FTIR study.
AB  - The interaction of an amino-terminal-truncated 139 amino-acids form of human
      acidic fibroblast growth factor with myo-inositol hexasulphate and low molecular
      weight (3500 g mol(-1)) heparin has been studied by isothermal titration
      calorimetry, differential scanning calorimetry and Fourier transform infrared
      spectroscopy. A slightly higher affinity for the monosaccharide has been
      measured. The binding of the ligands causes an increase of 13--15 degrees C in
      the melting temperature of the free protein (45 degrees C). From measured
      enthalpy and heat capacity changes, calculations of changes in accessible surface
      areas have been made. These calculations, together with infrared spectroscopy
      data, indicate that a small conformational change is induced by the binding of
      both ligands. This conformational change would affect the tertiary structure, not
      the secondary one.

PMID- 11311721
TI  - Solid-like mechanical behaviors of ovalbumin aqueous solutions.
AB  - Flow and dynamic mechanical properties of ovalbumin (OVA) aqueous solutions were
      investigated. OVA solutions exhibited relatively large zero-shear viscosity
      values under steady shear flow and solid-like mechanical responses against
      oscillating small shear strains, that is, the storage modulus was always larger
      than the loss modulus in the examined frequency range (0.1--100 rad s(-1)). These
      results suggest that dispersed OVA molecules arranged into a colloidal crystal
      like array stabilized by large interparticle repulsive forces. However, marked
      solid-like mechanical behaviors were detected even when electrostatic repulsive
      forces among protein molecules were virtually absent, which could not be
      explained solely on the basis of conventional Derjaguin--Landau--Verwey--Overbeek
      (DLVO) theory. Large non-DLVO repulsive forces seem to stabilize native OVA
      aqueous solutions.

PMID- 11311722
TI  - Structure--function relationships in bovine thymus 20S proteasome: a fluorimetric
      study.
AB  - The structure--function relationships occurring on the bovine thymus 20S
      proteasome, which exhibits the features of an immunoproteasome, have been
      studied. The investigation has been performed, essentially, using a fluorimetric
      approach, taking advantage either of the sensitivity of the complex to sodium
      dodecil sulfate and chaotropic agents (urea and guanidine hydrochloride) or of
      the presence, on the molecule, of a high number of tryptophan residues. The
      results obtained indicate that the perturbation or the oxidation of these
      residues affect the catalytic events taking place on the thymus proteasome and
      that the functional effects determined by SDS and chaotropic agents most likely
      occur through a series of progressive structural modifications leading to an
      inactive molecule. The presence of structural intermediates in the proteasome
      inactivation process suggests that thymus proteasome is a molecule characterized,
      at the same time, by structural flexibility (modulation of active sites) and
      structural stability (maintaining of the quaternary structure) in agreement with
      its crucial role in the cell life cycle.

PMID- 11311723
TI  - Kinetics of gelatin transitions with phase separation: T-jump and step-wise DSC
      study.
AB  - The isothermal gelation (or melting) of gelatin after fast cooling (or heating)
      steps is studied by using high sensitivity differential scanning micro
      calorimetry, in order to determine the dependence of the kinetic and
      thermodynamic parameters upon changes in composition and in temperature. The
      calorimetric heat flow curves, obtained according to defined temperature
      profiles, have been fitted with exponential functions (simple exponentials or
      stretched exponentials for the step-wise and for T-jump experiments,
      respectively). The gelation process of gelatin alone for t<300 min shows that the
      characteristic time tau and the fractional exponent are beta very sensitive to
      the concentration of gelatin chains and to the microscopic phase segregation due
      to the presence of another polymeric component.

PMID- 11311724
TI  - Recognition and oxidative metabolism of cyclodipeptides by hepatic cytochrome
      P450.
AB  - Possible recognition of peptide derivatives by hepatic cytochrome P450 3A has
      been suggested by binding and metabolism of numerous pseudopeptidic compounds
      such as ergot derivatives and cyclosporin. Natural linear or cyclic dipeptides
      containing hydrophobic amino acids produced by microorganisms and present in
      mammals are able to interact with the P450 active site through either iron-amine
      interactions (Type II) or hydrophobic Type I interactions. P450 3A from
      dexamethasone-treated rats or yeast-expressed P450 human 3A4 are the most potent
      in such interactions, which are particularly strong with peptides containing a
      histidyl residue. Some cyclodipeptides are rapidly transformed by rat cytochrome
      P450 3A to mono- or dihydroxylated metabolites, with turnovers around 3 nmoles
      min(-1) P450(-1). Linear peptides are poorly transformed in these conditions.
      This metabolism of cyclodipeptides occurs in 8 species including man. Such
      interactions and metabolism have only minor consequences in terms of P450 3A
      binding and metabolism of classical P450 3A substrates. These data reinforce the
      concept that, in addition to their effect on the regulation of P450 neosynthesis,
      naturally occurring endogenous peptides are also substrates of P450 3A. The
      physiological activities of these peptides may be modulated by their metabolism.

PMID- 11311725
TI  - Solution NMR structure of a model class A (apolipoprotein) amphipathic alpha
      helical peptide.
AB  - To better understand the structural determinants of the physical-chemical and the
      biological properties of Ac-18A-NH(2) (acetyl
      AspTrpLeuLysAlaPheTyrAspLysValAlaGluLysLeuLysGluAlaPhe-amide), we have determined
      its structure in 50% (v/v) trifluroethanol (TFE-d(3))/water mixture (5 mM
      potassium phosphate, pH 5.5, 310K) using two-dimensional proton NMR spectroscopy.
      Stereospecific assignments have been made for C(beta)H protons (all the residues
      except Ala and Val) and gammaCH(3) (Val) groups. Nuclear Overhauser effects are
      observed between the nonpolar side chains spaced at (i) and (i + 4) position in
      the primary sequence, e.g., Trp2 and Phe6, and Phe6 and Val10. This suggests that
      in addition to N-terminal acetyl and C-terminal amide groups, the amphipathic
      alpha helical structure of Ac-18A-NH(2) is further stabilized by interactions
      between the hydrophobic residues on the nonpolar face of the helix.

PMID- 11311726
TI  - Functional analysis of glucose-dependent insulinotropic polypeptide fusion
      proteins.
AB  - To generate functional fluorescently tagged glucose-dependent insulinotropic
      polypeptide (GIP), a series of GIP expression constructs were devised. These
      included G1 (complete preprohormone), G2 (lacking the C-terminal extension), G3
      (lacking both N- and C-terminal extensions), G4 (G2 fused to green fluorescent
      protein, GFP), and G5 (G3 fused to GFP). Expression of G5 in bacteria generated
      immunopositive GIP together with GFP fluorescence, while G4 generated only
      fluorescence without immunoreactivity. Transfection of NIH3T3 cells with cDNAs of
      G1, G3, G5, but not G2, G4, and EGFP, resulted in immunologically detectable GIP
      formation, although fluorescence could be detected in the latter two. GIP as well
      as GIP-GFP secreted by NIH3T3 cells significantly stimulated intracellular cAMP
      accumulation and Ca(2+) mobilization in SaOS2 cells. The GIP receptor antagonist
      GIP(7-30) abolished these responses. These results suggest that a GIP-GFP fusion
      protein seven times larger than the native peptide retains function and may be
      used as an in vivo probe to detect GIP receptor distribution and to explore GIP's
      biological roles.

PMID- 11311727
TI  - Peripheral administration of urocortin suppresses operant responding for food
      reward.
AB  - The effects of peripheral systemic administration of urocortin on operant
      responding to obtain food were investigated using three separate concentrations.
      The drug was administered intraparitoneally at a concentration of 10
      microg/ml/Kg, 5 microg/ml/Kg, and 0 microg/ml/Kg suspended in saline at a volume
      of 1 ml/Kg to Sprague-Dawley rats fifteen minutes prior to being exposed to an
      operant bar press task. Eleven subjects were used, each receiving a single
      injection of each concentration on separate days with the order of treatment
      counterbalanced. The results indicated that the administration of urocortin in a
      dose dependent manner reduced responding of food deprived subjects for a food
      reward in a thirty minute session. These data indicated that the peripheral
      administration of urocortin reduced the motivation of food deprived subjects to
      respond.

PMID- 11311728
TI  - Proadrenomedullin N-terminal 20 peptide (PAMP) inhibits food intake and gastric
      emptying in mice.
AB  - We found that proadrenomedullin N-terminal 20 peptide (PAMP) decreased dose
      dependently (3-30 nmol/mouse) food intake after intra-third cerebroventricular
      administration in fasted ddY mice. Gastric emptying also was delayed after
      central injection of PAMP. In our previous study, PAMP was demonstrated to elicit
      hyperglycemia via bombesin (BN) receptor. Then, we examined whether the effects
      of PAMP on feeding and gastric emptying were induced through BN receptor.
      Surprisingly, PAMP-induced reductions in feeding and gastric emptying rate were
      not blocked by a BN antagonist, [D-Phe(6), Leu-NHEt(13), des-Met(14)]-BN (6-14).
      PAMP suppressed feeding in mice lacking gastrin-releasing peptide receptor or BN
      receptor subtype-3. These results indicate that centrally administered PAMP
      inhibits food intake, involving the delayed gastric emptying, not through BN
      receptors but through selective PAMP receptor.

PMID- 11311729
TI  - Human pheochromocytomas, but not adrenal medulla, express glucagon-receptor gene
      and possess an in vitro secretory response to glucagon.
AB  - Glucagon-receptor mRNA was detected by reverse transcription-polymerase chain
      reaction in three human pheochromocytomas, but not in four normal adrenal
      medullas. Quantitative autoradiography demonstrated the presence of abundant
      [(125)I-Thyr(10)]glucagon binding sites in pheochromocytomas, which were
      displaced by both cold glucagon and the glucagon receptor antagonist Des
      His(1)[Glu(9)]glucagon amide (GR-A). Adrenal medulla was weakly labeled, and the
      binding was not displaced by GR-A. Glucagon enhanced epinephrine and
      norepinephrine release by pheochromocytoma slices, minimal and maximal effective
      concentrations being 10(-8) M and 10(-6) M. Adrenomedullary slices evidenced a
      weak catecholamine response only to 10(-5) M glucagon. GR-A abolished the
      secretory response to glucagon of pheochromocytomas, but not of adrenal medullas.
      Collectively, these findings indicate that human pheochromocytomas, but not
      adrenal medulla, express glucagon receptors and possess a marked secretory
      response to glucagon, thereby providing the rationale to explain the specificity
      of the glucagon provocative test in the diagnosis of pheochromocytoma.

PMID- 11311730
TI  - Effects of naltrexone and CCK on estrous behavior and food intake in Syrian
      hamsters.
AB  - Food deprivation inhibits estrous behavior in several species of rodents, but
      little is known about the neurotransmitter systems mediating this phenomenon. We
      determined whether partial blockade of opioid receptors by continuous infusion of
      naltrexone and/or acute peripheral injection of cholecystokinin (CCK)
      administration would overcome the suppressive effects of food deprivation on
      estrous behavior in Syrian hamsters. Contrary to expectation, naltrexone produced
      a slight suppression of estrous behavior, and systemic CCK administration had no
      effect. This dose of naltrexone was sufficient to reduce in vivo binding of
      [(3)H]naloxone in the brain, and both compounds affected other parameters such as
      food intake and body weight gain. Thus, the doses of CCK and naltrexone that were
      used were physiologically effective. These findings suggest that neither
      peripheral CCK nor opioid systems are likely to play a major role in the
      suppression of hamster estrous behavior by food deprivation.

PMID- 11311731
TI  - Naloxone blocks 'anxiolytic' effects of neuropeptide Y.
AB  - Intracerebroventricular injection of neuropeptide Y (NPY) produces potent
      'anxiolytic' effects in animal models of anxiety. Administration of opioid
      receptor antagonists suppresses NPY-induced food intake and thermogenesis. The
      present study examined whether the opiate antagonist naloxone would also suppress
      the 'anxiolytic' effects of neuropeptide Y. Following training and stabilization
      of responding in an operant conflict model of anxiety, rats were injected with
      either NPY or diazepam. Both NPY (veh., 2, 4, 6 microg, i.c.v.) and
      chlordiazepoxide (veh., 2, 4, 6 mg/kg, i.p.) produced a dose-dependent increase
      in punished responding in the conflict test. The 'anxiolytic' effects of NPY were
      not blocked by the administration of flumazenil (3, 6, 12 mg/kg, i.p.). The
      administration of naloxone (0.25-2.0 mg/kg, s.c.) antagonized the effects of NPY.
      Central administration of the selective mu opiate antagonist CTAP (1 microg,
      i.c.v.) partially blocked NPY-induced conflict responding. These results support
      the hypothesis that NPY may play an important role in experimental anxiety
      independent of the benzodiazepine receptor and further implicate the opioid
      system in the behavioral expression of anxiety.

PMID- 11311732
TI  - In vitro metabolism of opioid tetrapeptide agonists in various tissues and
      subcellular fractions from rats.
AB  - The metabolism of three mu-selective opioid tetrapeptide agonists, Tyr-D-Arg-Phe
      Nva-NH(2) (TArPN), Tyr-D-Arg-Phe-Phe-NH(2) (TArPP), and Tyr-D-Ala-Phe-Phe-NH(2)
      (TAPP), was investigated in different rat tissues. High metabolic activity (<20%
      peptide remaining after 30 min) was found against the three peptides in the
      kidney homogenate and against TArPN in spleen homogenate. Low metabolic activity
      (>80% peptide remaining after 30 min) was found for all peptides in brain
      homogenate and plasma, and for TArPN and TArPP in blood. The other tissue
      homogenates, prepared from the small and large intestine, liver and lung, all
      exhibited intermediate metabolic activity (20-80% peptide remaining after 30 min)
      against the peptides. In all tissues investigated, the tetrapeptides were
      metabolized at the C-terminal amide by deamidation.A further in depth metabolic
      investigation was performed in subcellular fractions isolated from three tissues
      (small intestine, liver and kidney). In the liver, the deamidation was
      predominantly localized to the mitochondrial/lysosomal fraction, while hydrolysis
      at the N-terminal Tyr residue was the major metabolic pathway in the
      microsomal/brush-border membrane fraction from the kidney and small intestine.

PMID- 11311733
TI  - [(125)I]EYF: a new high affinity radioligand to neuropeptide FF receptors.
AB  - [(125)I]EYF ([(125)I]EYWSLAAPQRFamide), a new radioiodinated probe derived from a
      peptide present in the rat Neuropeptide FF precursor (EFWSLAAPQRFamide, EFW-NPSF)
      was synthesized and its binding characteristics investigated on sections of the
      rat spinal cord and on membranes of mouse olfactory bulb. In both tissues,
      [(125)I]EYF binding was saturable and revealed a very high affinity interaction
      with a single class of binding sites in rat and mouse (K(D) = 0.041 and 0.019 nM,
      respectively). Competition studies showed that [(125)I]EYF bound to one class of
      binding sites exhibiting a high affinity for all the different peptides the
      precursor could generate (NPA-NPFF, SPA-NPFF, NPFF, EFW-NPSF, QFW-NPSF) with the
      exception of NPSF which displayed a low affinity. Autoradiographic studies
      demonstrated that [(125)I]EYF binding sites were fully inhibited by a synthetic
      Neuropeptide FF agonist (1DMe) in all areas of the rat brain. The density of
      [(125)I]EYF binding sites was high in the intralaminar thalamic nuclei, the
      parafascicular thalamic nucleus and in the superficial layers of the dorsal horn.
      Non specific binding reached 5-10% of the total binding in all brain areas.
      Similarly, in mouse brain experiments, the non-specific binding was never
      superior to 10%. These findings demonstrate that putative neuropeptides generated
      by the Neuropeptide FF precursor and containing the NPFF or NPSF sequences should
      bind to the same receptor. Furthermore, these data indicate that [(125)I]EYF is a
      useful radiolabeled probe to investigate the NPFF receptors; its major advantages
      being its high affinity and the very low non-specific binding it induces.

PMID- 11311734
TI  - Opioid peptides attenuate blood pressure increase in acute respiratory failure.
AB  - Plasma opioid peptides, norepinephrine, atrial natriuretic factor (ANF) and blood
      pressure (BP) were assessed in 24 chronic obstructive pulmonary disease patients
      with acute respiratory failure. Hypoxemic-hypercapnic patients had high BP, beta
      endorphin, Met-enkephalin and dynorphin B, whereas hypoxemic-normocapnic and
      hypoxemic-hypocapnic patients showed normal BP, high beta-endorphin, and normal
      Met-enkephalin and dynorphin B. Norepinephrine and ANF were high in all patients,
      particularly in hypoxemic-hypercapnic patients. Infusion with the opioid
      antagonist naloxone hydrochloride significantly increased systolic blood pressure
      (SBP) in hypoxemic-hypercapnic (182.0 +/- 3.2 versus 205.1 +/- 3.0 mmHg; P <
      0.01), hypoxemic-normocapnic (149.3 +/- 1.8 versus 169.1 +/- 2.2 mmHg; P < 0.01)
      and hypoxemic-hypocapnic (147.3 +/- 1.3 versus 166.8 +/- 2.2 mmHg; P < 0.01)
      patients, norepinephrine in hypoxemic-hypercapnic patients (3583.2 +/- 371.8
      versus 5371.3 +/- 260.0 fmol/ml; P < 0.01), and reduced ANF in hypoxemic
      normocapnic (18.3 +/- 0.8 versus 11.9 +/- 1.0 fmol/ml; P < 0.05) and hypoxemic
      hypocapnic (18.1 +/- 1.2 versus 12.1 +/- 2.1 fmol/ml; P < 0.05) patients. These
      results indicate that the endogenous opioid system attenuates SBP responses in
      acute respiratory failure by affecting norepinephrine or ANF release.

PMID- 11311735
TI  - Mechanisms underlying increased release of endothelin-1 from aorta in diabetic
      rats.
AB  - To clarify the mechanism underlying increased endothelin-1 release in diabetic
      rats, we examined its release from thoracic aortas obtained from streptozotocin
      induced diabetic rats. The methoxamine-induced contraction was significantly
      inhibited by BQ-123 plus BQ-788 (specific antagonists for ET(A) and ET(B)
      receptors) in diabetic, but not control rats. Preincubation with phosphoramidon
      also inhibited the methoxamine-induced contraction in diabetic but not control
      rats. The expression of prepro endothelin-1 mRNA was significantly enhanced in
      aortas from streptozotocin-induced diabetic rats. These results suggest that the
      increases in the basal and alpha-agonist-induced release of endothelin-1 in the
      diabetic state may be due to an overexpression of the mRNA for prepro endothelin
      1.

PMID- 11311736
TI  - About 8- and approximately 84-h rhythms in endotheliocytes as in endothelin-1 and
      effect of trauma.
AB  - Population densities (PD) of capillaries (C) and endotheliocytes (E) were
      determined in pinnal dermis of C57BL mice before and after trauma. Moving (and
      overall) least-squares spectra before trauma detected in EPD (versus CPD)
      pronounced 3.5-day (circasemiseptan) and 8-h oscillations corresponding to
      components of the endothelin-1 chronome in human blood plasma reported earlier.
      Circadians were more pronounced in CPD. After trauma, circasemiseptan
      oscillations appeared also in CPD; their period gradually shortened and in two
      weeks split into about 2.5- and about 4.5-day oscillations; and circadian
      components became very pronounced. The pre-traumatic chronome was not restored
      within three weeks following trauma.

PMID- 11311737
TI  - Delay of neutrophil apoptosis by the neuropeptide substance P: involvement of
      caspase cascade.
AB  - Neutrophil apoptosis is an important event in the resolution of inflammation. The
      role of substance P (SP) in neutrophil apoptosis has not been previously
      investigated. We found that substance P delays apoptosis in neutrophils. Human
      neutrophils were isolated and cultured up to 24 hours. Apoptosis was detected by
      light and electron microscopy, as well as DNA-fragmentation assays. Substance P
      delayed the spontaneous apoptosis of neutrophils at 6, 12, 18 and 24 hours in a
      dose-dependent fashion in the range of 10-100 microM. Whereas the both peptide
      neurokinin-1 (NK-1) receptor antagonists [D-Pro(2), D-Trp(7,9)]-SP and GR 82334
      inhibited the substance P effect on neutrophils, the nonpeptide NK(1) receptor
      antagonist L-703.606 itself, an analogue of CP-96,345, induced apoptosis of
      neutrophils. Surprisingly, the effect of L-703.606 could be prevented by
      substance P. Western blotting results showed that the neuropeptide substance P
      inhibited the spontaneous apoptosis-associated caspase-3 activation in the same
      concentration range as described above. Parallel the inhibition of cleavage of
      focal adhesion kinase (FAK), a substrate of caspases could be observed by
      substance P. In conclusion, our results extend the range of biological effects of
      the neuropeptide substance P and provide new insight to the role of this
      tachykinin in the modulation of the inflammatory response by the nervous system.

PMID- 11311738
TI  - Liposomal VIP potentiates DNA synthesis in cultured oral keratinocytes.
AB  - The purpose of this study was to determine whether association of vasoactive
      intestinal peptide with sterically stabilized liposomes (VIP on SSL) amplifies
      DNA synthesis evoked by the peptide in cultured chemically transformed hamster
      oral keratinocytes (HCPC-1) and, if so, whether this response in mediated, in
      part, by SSL-induced inactivation of neutral endopeptidase 24.11 (NEP; EC
      3.4.24.11) and angiotensin I-converting enzyme (ACE; EC 3.4.15.1), two
      ectoenzymes that modulate HCPC-1 cell growth, in these cells. We found that VIP
      (10(-9)-10(-6) M) alone elicited a modest, albeit significant, concentration
      dependent increase in DNA synthesis in HCPC-1 cells that was maximal after 48-72
      h incubation (p < 0.05). VIP on SSL potentiated DNA synthesis in these cells
      relative to VIP alone. The magnitude of VIP on SSL-induced responses was 1.2-1.6
      fold higher than that of VIP alone with maximal effects observed at 10(-9) M and
      10(-6) M after 72- and 48-h incubation, respectively. Empty SSL had no
      significant effects on DNA synthesis. Empty SSL and VIP on SSL had no significant
      effects on NEP 24.11 and ACE activity in HCPC-1 cells. Collectively, these data
      indicate that association of VIP with SSL potentiates DNA synthesis in cultured
      oral keratinocytes relative to VIP alone and that this response is not related to
      non-specific effects of SSL.

PMID- 11311739
TI  - Phorbol ester differentially regulates oxytocin receptor binding activity in
      hypothalamic cultured neurons and astrocytes.
AB  - Hypothalamic cultured neurons and astrocytes were used to investigate the
      cellular mechanisms underlying the oxytocin receptor-mediated downregulation
      through a possible involvement of protein kinase C (PKC). For this purpose, the
      effects of PKC activators, inhibitor and of OT on OT receptor binding activity
      were compared in both cultures. In neurons, phorbol-myristate-acetate (PMA), a
      potent PKC activator, increased the binding of an OT receptor antagonist whereas
      in astrocytes, a decrease was observed. Pre-treatment of the cells with
      bisindolylmaleimide (10(-4) M), a PKC inhibitor, prevented the PMA-induced up-
      and downregulation. In contrast, receptor downregulation resulting from treatment
      of both cells with OT (10(-9) M) was not affected by the PKC inhibitor. On the
      other hand, when PMA (10(-7) M) was tested along with OT (10(-9) M), a subsequent
      decrease in ligand binding was observed in astrocytes. In neurons, PMA attenuated
      the OT-induced downregulation. Structural analysis of neuron and astrocyte OT
      receptor mRNA by RT-PCR, subcloning and sequencing, demonstrated identical
      sequence to rat uterine receptor. In conclusion, these data suggest that
      activation of PKC has opposite effect on OT receptor binding activity in neurons
      and astrocytes but they do not support the involvement of PKC in the OT-induced
      downregulation.

PMID- 11311740
TI  - Beta endorphin-like immunoreactivity in human aqueous humor and crystalline lens.
AB  - We measured the concentration of beta-endorphin (beta-End) in plasma, as well as
      in aqueous humor and crystalline lens removed during cataract surgery. beta-End
      was detected both in the aqueous humor and in the crystalline lens. The
      concentration of beta-End in the aqueous humor corresponded to almost the half of
      the plasma level (2.18 fmol/l and 4.55 fmol/l). Endogenous beta-End is presumed
      to enter the intraocular structures by passive diffusion.

PMID- 11311742
TI  - New hypotheses for the GPCR 3D arrangement based on a molecular model of the
      human sweet-taste receptor.
AB  - A molecular model of the human sweet-taste receptor has been inferred from
      superpositions of 3D maps of sweetener interaction sites (themselves previously
      deduced from extensive structure-activity relationship studies on highly potent
      sweeteners) onto three well-known G protein-coupled receptors (GPCRs)-rhodopsin,
      beta(2)- and alpha(2A)-adrenergic receptors-assumed to be linked by common
      evolutionary origins. The model gives new answers to old questions on the GPCR 3D
      structure, such as on the orientation and arrangement of the binding helices,
      their interaxial distances, radial orientations and relative heights. The model
      should be useful as a new approach to the rational design of drugs.

PMID- 11311741
TI  - The case for gastrin-releasing peptide acting as a morphogen when it and its
      receptor are aberrantly expressed in cancer.
AB  - Gastrin-releasing peptide (GRP) and its receptor (GRP-R) are frequently expressed
      by cancers of the gastrointestinal tract, breast, lung, and prostate. Most
      studies have found that GRP and its amphibian homologue bombesin act to increase
      tumor cell proliferation, leading to the hypothesis that this peptide hormone is
      a mitogen important for the growth of various cancers. Yet GRP/GRP-R co
      expression in cancer promotes the development of a well-differentiated phenotype;
      while multiple studies suggest that the presence of these 2 proteins confer a
      survival advantage. Along with recent reports showing that GRP and its receptor
      critically regulate aspects of colon and lung organogenesis, we argue that these
      proteins do not function primarily as mitogens when aberrantly expressed in
      cancer. Rather, we postulate that GRP/GRP-R are onco-fetal antigens that function
      as morphogens, with their effect on tumor cell proliferation being a component
      property of their ability to regulate differentiation. Thus aberrant GRP/GRP-R
      expression in cancer recapitulates, albeit in a dysfunctional manner, their
      normal role in development.

PMID- 11311743
TI  - Cyclooxygenase inhibitors--current status and future prospects.
AB  - Prostaglandins are formed from arachidonic acid by the action of cyclooxygenase
      and subsequent downstream synthetases. Two closely related forms of the
      cyclooxygenase have been identified which are now known as COX-1 and COX-2. Both
      isoenzymes transform arachidonic acid to prostaglandins, but differ in their
      distribution and their physiological roles. Meanwhile, the responsible genes and
      their regulation have been clarified. COX-1, the pre-dominantly constitutive form
      of the enzyme, is expressed throughout the body and performs a number of
      homeostatic functions such as maintaining normal gastric mucosa and influencing
      renal blood flow and platelet aggregation. In contrast, the inducible form is
      expressed in response to inflammatory and other physiological stimuli and growth
      factors, and is involved in the production of the prostaglandins that mediate
      pain and support the inflammatory process. All the classic NSAIDs inhibit both
      COX-1 and COX-2 at standard anti-inflammatory doses. The beneficial anti
      inflammatory and analgesic effects are based on the inhibition of COX-2, but the
      gastrointestinal toxicity and the mild bleeding diathesis are a result of the
      concurrent inhibition of COX-1. Agents that inhibit COX-2 while sparing COX-1
      represent a new attractive therapeutic development and could represent a major
      advance in the treatment of rheumatoid arthritis and osteoarthritis. Apart from
      its involvement in inflammatory processes, COX-2 seems to play a role in
      angiogenesis, colon cancer and Alzheimer's disease, based on the fact that it is
      expressed during these diseases. The benefits of specific and selective COX-2
      inhibitors are currently under discussion and offer a new perspective for a
      further use of COX-2 inhibitors.

PMID- 11311744
TI  - Substituted benzopyranobenzothiazinones. Synthesis and estrogenic activity on MCF
      7 breast carcinoma cells.
AB  - In the search for new agents with estrogenic activity mediated by estrogen
      receptors (ER), six 6,12-dihydro-1-benzopyrano[3,4-b][1,4]benzothiazin-6-ones 3a
      f were synthesized. These compounds were readily prepared by the addition of 2
      aminothiophenol 2 to substituted 4-hydroxycoumarin derivatives 1a-e. The
      estrogenic effect has been evaluated on the proliferation of MCF-7 breast
      adenocarcinoma cells and the specificity of described compounds was evaluated by
      the inhibition of their effect by ICI 182,780, an antiestrogenic compound. Among
      the compounds tested, 6,12-dihydro-3-methoxy-1-benzopyrano[3,4
      b][1,4]benzothiazin-6-one 3e and 6,12-dihydro-3-hydroxy-1-benzopyrano[3,4
      b][1,4]benzothiazin-6-one 3f exhibited an ER-dependent proliferation and a high
      binding affinity to ER, but a moderate capacity to activate the transcription of
      a reporter gene. Their pharmacological profiles are defined by their binding
      properties and their mechanism of action by computational modelling studies.

PMID- 11311745
TI  - Design of new small cyclic melanocortin receptor-binding peptides using molecular
      modelling: Role of the His residue in the melanocortin peptide core.
AB  - The conserved core of melanocyte stimulating hormones (MSH), His-Phe-Arg-Trp, was
      probed by comparing a cyclic pentapeptide containing His-DPhe-Arg-Trp, with three
      structurally similar cyclic peptides, that lacked the His residue. All three
      peptides bound to the MC(1), MC(3), MC(4) and MC(5) receptors with similar
      affinities. Molecular modelling indicated that the 3D structure of the DPhe-Arg
      Trp of all three peptides were closely similar. The data indicate that the His
      residue of the small rigid cyclic MSH core peptides does not participate in
      binding with the melanocortin receptors.

PMID- 11311746
TI  - A feature based pharmacophore for Candida albicans MyristoylCoA: protein N
      myristoyltransferase inhibitors.
AB  - A three-dimensional pharmacophore model has been generated for Candida albicans
      MyristoylCoA: protein N-myristoyltransferase (NMT) inhibitors, using the software
      program CATALYST. The in vitro NMT inhibitory activity of a series of peptidic
      inhibitors was used for pharmacophore generation. The effect of altering the
      control parameters and feature selection was studied to arrive at the
      pharmacophore model. The selection of the best hypothesis model was based on the
      total cost, predictive ability, difference in the cost from the null hypothesis
      and alignment of the training set compounds on to the hypothesis. The
      pharmacophore model selected has four features; one hydrophobic, two hydrogen
      bond acceptor and one positive ionisable function. Groups identified as necessary
      by scanning alanine mutagenesis studies of the peptidic substrate of C. albicans
      NMT, have been identified as pharmacophore features. Comparison of the ligand
      binding with the enzyme in the crystal structure of NMT and that proposed by the
      phamacophore is consistent. The pharmacophore thus generated can be used as a
      template for designing non-peptidic inhibitors of NMT.

PMID- 11311747
TI  - 5-HT(6) receptor antagonists: lead optimisation and biological evaluation of N
      aryl and N-heteroaryl 4-amino-benzene sulfonamides.
AB  - RO-04-6790 (6a) has been identified in a random screen for 5-HT(6) receptor
      antagonists. In a medicinal chemistry optimisation program a series of analogs
      comprising N-heteroaryl- and N-arylbenzenesulfonamides have been synthesised and
      investigated for their binding affinity. Compounds with a logD profile indicative
      of brain penetration have been subjected to in vivo testing for reversal of a
      scopolamine-induced retention deficit in a passive avoidance paradigm.

PMID- 11311748
TI  - 10-Phenylbutyryl-substituted anthracenones as inhibitors of keratinocyte growth
      and LTB(4) biosynthesis.
AB  - A recent observation that phenylbutyryl anthracenone 2, an analogue of the
      antipsoriatic anthralin, is a potent inhibitor of leukotriene B(4) (LTB(4))
      biosynthesis has prompted a search of other anthracenones with improved
      antiproliferative activity. In that direction, a limited number of analogues
      related to 2 have been prepared and evaluated in the HaCaT keratinocytes
      proliferation and in the polymorphonuclear leukocyte LTB(4) assay. The 4-methoxy
      analogue 2a and the side chain methylated 2l retain the full inhibitory activity
      of 1 against LTB(4) biosynthesis while their antiproliferative activity is
      markedly enhanced and comparable to that of the antipsoriatic anthralin. In
      contrast to anthralin, cytotoxic effects against cell membranes are strongly
      reduced as documented by the LDH activity released from cytoplasm of
      keratinocytes.

PMID- 11311749
TI  - Synthesis and inhibitory activity towards human leukocyte elastase of new 7alpha
      methoxy and 7alpha-chloro (2-acyloxymethyl) cephem derivatives.
AB  - Some new cephem derivatives of types 4 and 5, viewed as analogues of type I
      esters in which the atomic sequence of the C-2 ester group is formally inverted,
      were synthesised and tested in vitro for their inhibitory activity towards human
      leukocyte elastase and porcine pancreatic elastase. An examination of the
      inhibition data obtained for the new type 4 and 5 derivatives, while exhibiting a
      considerable reduction in their activity against porcine pancreatic elastase,
      indicated that these compounds still maintain an appreciable inhibitory activity
      against human leukocyte elastase. On this basis the new type of C-2 substitution
      appears to contribute to the research of new, potentially interesting,
      cephalosporinic human leukocyte elastase inhibitors.

PMID- 11311750
TI  - Synthesis and neuromuscular blocking activity of 16beta-piperidinosteroidal
      derivatives.
AB  - The synthesis and pharmacological profiles of some new steroidal mono- and
      bisquaternary ammonium derivatives have been described. The compounds featured
      have been conceptually derived structurally from two lead structures: pancuronium
      bromide 1 and chandonium iodide 2. In vitro and in vivo neuromuscular blocking
      studies have indicated the monoquaternary compound 15 to be less active than the
      bisquaternary compounds 10 and 11. The compound 11 has been found to be more
      active than d-tubocurarine.

PMID- 11311751
TI  - Synthesis of a set of ethyl 1-carbamoyl-3-oxoquinoxaline-2-carboxylates and of
      their constrained analogue imidazo.
AB  - The synthesis and glycine/NMDA and AMPA receptor affinities of a set of ethyl (+/
      ) 1-N-carbamoyl-1,2,3,4-tetrahydro-3-oxoquinoxaline-2-carboxylates 1-11 and those
      of their constrained analogue (+/-) 1,2,3,3a,4,5-hexahydroimidazo[1,5
      a]quinoxaline-1,3,4-triones 12-24 are reported. Compounds 1-11 bear a side-chain
      at position 1 which has been spatially constrained in compounds 12-24. Most of
      the reported tricyclic derivatives 12-24 showed glycine/NMDA binding activity
      comparable to that of their corresponding bicyclic analogues 1-11 providing
      further evidence that the spatial orientation of the side-chain is an important
      structural requirement for glycine/NMDA receptor antagonists.

PMID- 11311752
TI  - Synthesis and stereoselective kappa-receptor binding of methylated analogues of
      GR-89.696.
AB  - Stereoselective synthesis of all four stereoisomers of methylated analogues 8 of
      the kappa-receptor agonist GR-89.696 is presented. Starting with orthogonally
      protected piperazine derivatives (R,R)-4 and (S,S)-4, the reaction sequence
      involves oxidation, reductive amination and modification of the piperazine
      nitrogen protective groups. The configuration of the stereocentre in alpha
      position to the pyrrolidine moiety is determined by X-ray structure analysis of
      (R,S)-8. In receptor-binding studies with the radioligand U-69.593, the
      stereoisomer with (S)-configuration at both stereogenic centres (S,S)-8 displayed
      the highest kappa-receptor affinity with a K(i)-value of 0.67 nM.

PMID- 11311754
TI  - Anaemia in pregnancy in sub-Saharan countries.

PMID- 11311755
TI  - Case reports; original, educational or sexy--yes please, just rare--no thanks.

PMID- 11311756
TI  - Management and monitoring of severe preeclampsia.
AB  - Preeclampsia is associated with increased maternal and perinatal morbidity and
      mortality. Preeclampsia is more than pregnancy-induced hypertension. The
      hypertension is only one manifestation of an underlying multifactorial,
      multisystem disorder, initiated early in pregnancy. In established severe disease
      there is volume contraction, reduced cardiac output, enhanced vascular
      reactivity, increased vascular permeability and platelet consumption. Medical
      treatment of severe hypertension in pregnancy is required. The more controversial
      issues are the role of pharmacological treatment in conservative management of
      severe preeclampsia aiming at prolongation of pregnancy, the ability of such
      therapy to modify the course of the underlying systemic disorder and the effects
      on fetal and maternal outcome. This paper presents an overview concerning the
      current developments in management and monitoring of severe preeclampsia.
      Controversial topics such as the role of plasma volume expansion in preeclampsia,
      expectant versus aggressive management of severe preeclampsia remote from term,
      and pharmacological interventions in the management of eclampsia and the HELLP
      syndrome are addressed.

PMID- 11311757
TI  - Theories of endometriosis.
AB  - Endometriosis is characterised by the presence of abnormally located tissue
      resembling the endometrium with glands and stroma. Several hypotheses have
      attempted to explain the development of such tissue. The oldest theory, that of
      metaplasia, suggests that under diverse influences coelomic tissue could be
      transformed into endometrium. The most often cited theory, that of implantation,
      proposes that the physiological phenomenon of endometrial reflux in the fallopian
      tubes during menstruation may, in certain conditions, overcome local defense
      mechanisms, implant, and proliferate. The peritoneal fluid in unaffected women
      possesses the capacity to prevent endometriotic tissue from becoming established.
      The reasons for the occurrence of endometriosis and its consequences (pain,
      sterility, adhesions) are probably numerous and involve the endometrium, the
      immune system (macrophages, natural killer cells), the peritoneum, and fallopian
      tubes. The failure to clear the peritoneal cavity of fragments of endometrium
      could cause a state of local inflammation with hyperactivation of macrophages
      secreting a variety of different compounds. Some of these compounds may bring
      about metaplasia of the peritoneum or the development of Mullerian residues.

PMID- 11311758
TI  - "Fellow gynaecologists, help your patients stop smoking!".
AB  - BACKGROUND: Age-adjusted mortality from lung cancer in American women has
      increased dramatically and has even exceeded breast cancer mortality.
      Gynaecologists, are often involved as primary actors in prevention strategies but
      may not be aware of this epidemic. This is especially true in Europe where, lung
      cancer mortality for women is three times lower than in the US. OBJECTIVE: We
      aimed to investigate whether smoking data could explain the lower death rates
      found in Europe. METHOD: Analysis of smoking and mortality data in different
      European countries. RESULTS: European lung cancer mortality data shows a huge
      heterogeneity between countries (ranging from as low as 5/100,000 to 37/100,000).
      A strong correlation exists between the smoking prevalence in different
      countries, in women aged 55 years and more, and the mortality rates from lung
      cancer (R(2)=0.8; p<0.001). Smoking prevalence of younger women is much higher
      today than that of women over 55 years. CONCLUSION: These data strongly suggest
      that the epidemic of lung cancer will explode in Europe during the next decades.
      Gynaecologists should be aware of this and spend the necessary time to inform
      women adequately about the dangers of smoking and help them to quit.

PMID- 11311759
TI  - Antiphospholipid syndrome and recurrent miscarriages.
AB  - Sixty percent of recurrent spontaneous abortions are unexplained.
      Antiphospholipid syndrome is a multisystem disease with the predominant features
      of venous and arterial thrombosis, recurrent pregnancy loss, foetal death and the
      presence of antiphospholipid antibodies. Many epidemiological studies focus on
      antiphospholipid autoantibodies syndrome (APS) as a cause of recurrent
      spontaneous abortion (RSA). It is found that 7-25% of RSA would have APS as the
      main risk factor. 'Association not being synonymous with cause', the proportion
      of abortions due to the APS is difficult to estimate for several reasons:
      definition of recurrent abortion is variable, the assays for antiphospholipid
      antibodies are not well standardised, inclusion of patients in the study group
      according to the antibodies titre is author dependent. Recent studies suggest
      association of antiphospholipid antibodies syndrome not only with recurrent
      abortions but also with infertility. New mechanisms are described by which
      antiphospholipid antibodies could cause placental thrombosis and infarction,
      acting directly on the surface anticoagulant expressed on trophoblastic cells.
      Only lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) assays are
      sufficiently standardised to be usable in routine. Testing for other
      antiphospholipid antibodies (aPLs) should remain investigational. Several
      treatments have been proposed: low doses of aspirin, low or immunosuppressive
      doses of corticosteroids, and preventive or effective dose of heparin,
      intravenous immunoglobulin.

PMID- 11311760
TI  - Mucin-like carcinoma-associated antigen (MCA) during normal pregnancy.
AB  - OBJECTIVE: To assess the usefulness of Mucin-like carcinoma-associated antigen
      (MCA) in monitoring pregnant patients with breast cancer. STUDY DESIGN: Maternal
      serum (MS) and amniotic fluid (AF) antigen values were measured by an enzyme
      immunoassay in 30 pregnant women during the second trimester, in 28 during the
      third and in 26 at parturition. Sera only from 26 women in the first trimester
      and from 26 healthy, non-pregnant women (controls) were also analyzed. RESULTS:
      Maternal serum MCA concentrations increased significantly with gestational age
      (p<0.0001). The frequency of elevated serum values was 5% in the first, 35% in
      the second and 100% in the third trimester and at parturition. Antigen values in
      AF were markedly higher than those in MS (p<0.0001) and increased also
      significantly with advancing gestation (p<0.0001). A strong correlation was
      observed between MS and AF antigen values (r=0.77, p<0.0001). Maternal serum
      values at parturition were dependent on the mode of delivery, being higher in the
      cases who delivered vaginally, compared to those delivered by elective caesarean
      section (p<0.006). CONCLUSION: Our data suggest that pregnancy affects
      significantly maternal serum MCA. Consequently, MCA seems to be a non-reliable
      marker in monitoring pregnant patients.

PMID- 11311761
TI  - Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and
      viral shedding.
AB  - Neonatal herpes affects about 1 in 15,000 newborns and the prognosis for
      disseminated disease with encephalitis is poor. We investigated whether acyclovir
      prophylaxis in late pregnancy effectively reduces the risk of viral shedding and,
      hence, of mother-to-child transmission at delivery. A prospective study was
      conducted. Pregnant women who had at least one episode of genital herpes during
      pregnancy were randomly assigned to two groups: group 1 (n=167) received oral
      acyclovir from 36 weeks of gestation to term; group 2 (n=121) received no
      treatment. Group 3 (n=201) comprised women not given prophylaxis who had a
      history of genital herpes, but no active episodes during pregnancy. No specific
      instruction were set up for obstetrical management except for cesarean section in
      case of a suspected herpes lesion at the time of labor. The rate of Cesarean
      section was 8.4% in group 1, 16.5% in group 2, and 9.9% in group 3 (p<0.001). 75%
      of cesareans in group 2 and 10% in group 3 were done for genital herpes.
      Percentage of viral shedding was, respectively, 0% (group1), 5% (group2), and
      0.5%(group3) (p<0.05). These findings underline the value of antiviral
      prophylaxis in late pregnancy for women with a known history of genital herpes.
      Such prophylaxis only partly prevents neonatal herpes infection, because it is
      not applicable to patients with no known clinical history but may excrete the
      virus.

PMID- 11311762
TI  - Alterations of maternal and fetal leptin concentrations in hypertensive disorders
      of pregnancy.
AB  - OBJECTIVES: To investigate whether hypertensive disorders of pregnancy alter the
      maternal and fetal leptin levels. METHODS: Fifty primigravidas between 28 and 34
      weeks of gestation were divided into three groups: group A consisted of 17 normal
      pregnant women with a mean gestational age of 31 weeks, group B consisted of 15
      women with gestational hypertension without proteinuria with a mean gestational
      age of 30 weeks and group C consisted of 18 pre-eclamptic women with a mean
      gestational age of 31 weeks. RESULTS: The pre-eclamptics had significantly higher
      serum leptin levels than those in normal pregnancies (p<0.001) but no difference
      was noted between normal and gestational hypertensive pregnancies. Pre-eclamptic
      women had significantly higher umbilical vein leptin levels (4.68+/-1.66ng/ml)
      compared to normal pregnancies (1.92+/-0.71ng/ml) and those with gestational
      hypertension (2.47+/-0.81ng/ml). CONCLUSIONS: Pre-eclampsia is associated with an
      increase in maternal plasma leptin levels and fetal of leptin production
      increases in gestational hypertension and even more in pre-eclampsia.

PMID- 11311763
TI  - Use of omeprazole during pregnancy--no hazard demonstrated in 955 infants exposed
      during pregnancy.
AB  - OBJECTIVES: To evaluate the magnitude of possible fetal risks involved in
      maternal use of omeprazole during pregnancy. STUDY DESIGN: Infants whose mothers
      used omeprazole during pregnancy were identified from the Swedish Medical Birth
      Registry. A total of 955 exposed infants born in 1995-1999 were identified: 863
      of which were exposed in early pregnancy and 131 later in pregnancy and 39 who
      had been exposed both in early and late pregnancy. Delivery outcome was studied:
      presence of congenital malformations, perinatal survival, low birth weight, low
      Apgar score and hospitalization up to the end of 1997. RESULTS: No clear-cut
      indication of ill effects were seen. Five infants were stillborn and the rate of
      congenital heart defects was slightly increased, but both effects may be random.
      CONCLUSIONS: The present dataset and previously published data give no reason for
      concern after exposure for omeprazole during pregnancy.

PMID- 11311764
TI  - Remote prognosis of primiparous women with preeclampsia.
AB  - OBJECTIVE: To describe the maternal characteristics of pregnancy and perinatal
      outcome of primiparous women with preeclampsia, to determine the recurrence rate
      and to define the maternal risk factors for preeclampsia in subsequent
      pregnancies. METHODS: A retrospective cohort study. Two groups of patients were
      defined: the study group consisted of 380 primiparous women with preeclampsia,
      and in a control group of 385 primiparous women without preeclampsia. The
      patients were followed during their consecutive deliveries. Multiple logistic
      regression analysis was used to determine the independent risk factors for the
      recurrence of preeclampsia in the second pregnancy. RESULTS: In the study and the
      control group there were a total of 1207 and 1293 deliveries, respectively. Of
      the 380 primiparous women in study group, 305 (80%) were identified as suffering
      from mild preeclampsia, 64 (17%) from severe preeclampsia, 10 (2.6%) from super
      imposed preeclampsia and only one (0.3%) had eclampsia. Primiparous with severe
      preeclampsia had a significantly higher rate of preterm delivery then those with
      mild preeclampsia (34 versus 11% respectively, P<0.0001). In addition, the study
      group had significantly higher rate of perinatal mortality (3.4 versus 0.3%,
      P=0.013) and perinatal complications. The recurrence rate of preeclampsia was
      significantly higher in the study group (25% versus 1.9%, P<0.0001). When
      adjusted for confounding variables, gestational diabetes was strongly associated
      with the recurrence of preeclampsia in the second pregnancy (OR 3.72 95% CI 1.45
      9.53). CONCLUSION: Primiparous women with preeclampsia are at an increased risk
      for recurrence in subsequent pregnancies. Gestational diabetes in primiparous
      women with preeclampsia is an independent risk factor for developing preeclampsia
      in the second pregnancy.

PMID- 11311765
TI  - Results of recto-vaginal fistula repair: retrospective analysis of 48 cases.
AB  - OBJECTIVE: To evaluate the long-term outcome of the Musset technique of recto
      vaginal fistula (RVF) repair. STUDY DESIGN: During the years 1992-1998, 48 women
      underwent recto-vaginal fistula repair. A retrospective study in a university
      tertiary referral center was conducted. RESULTS: The main etiologies were
      obstetrical trauma (25), local infection (11), inflammatory disease (7), and post
      surgery (3). Thirty women (63%) had a previous fistula repair failure. The mean+/
      S.D. fistula diameter was 1.4+/-1.0, and in 40% of the patients the fistula
      diameter was >2.5cm. In 19 cases (39.6%) there was a complete opening of the
      perineum and anal sphincter. Gas and stool incontinence before the operation were
      noted in 85 and 75% of the patients, respectively. Successful anatomic results
      were achieved in all patients. Five patients were re-operated due to gas and
      stool incontinence, and all but one had satisfactory anatomic and functional
      satisfactory results. The success rates in women with Crohn's disease and with a
      previous RVF repair failure were 100 and 98%, respectively. No major intra or
      postoperative complications were noted. CONCLUSION: The Musset procedure provide
      excellent anatomic and functional results and women with Crohn's disease or
      previous RVF repair have comparable long-term results.

PMID- 11311766
TI  - Laparoscopic surgery of dermoid cysts--intraoperative spillage and complications.
AB  - OBJECTIVE: To assess the risks of complications including intraoperative spillage
      following laparoscopic dermoid cyst enucleation. STUDY DESIGN: A retrospective
      case series comparison of 390 patients who had surgery at our hospital from 1992
      to 1998 for teratomas of the ovary. RESULTS: 43 patients were treated with
      laparotomy. Two malignant teratomas were observed in this group. In seven
      patients, the dermoid cysts were removed as part of a vaginal hysterectomy. Three
      hundred and forty patients had surgery via laparoscopy. Enucleation of the
      dermoid cyst in toto using a salvage bag for removal was only possible in few
      cases without contamination of the abdominal cavity by spillage of cyst contents.
      There were no serious complications in any patients including those with
      laparoscopic cystectomies and intraperitoneal spill. CONCLUSION: The laparoscopic
      treatment of benign teratomas is a safe procedure. Primary laparotomy as well as
      adenectomy is also to be taken into consideration with young patients, if
      suspicion of malignancy, rapid growth, doubtful infiltration or large size of
      tumor is present.

PMID- 11311767
TI  - The influence of tibolone upon serum leptin levels in post-menopausal women.
AB  - OBJECTIVE: To estimate serum leptin levels in post-menopausal women, to relate
      these to the duration of the post-menopausal period, and to body mass index
      (BMI), and to assess the influence of tibolone on them. METHODS: Fifteen women
      (age 49-64 years) were included. Three groups were studied; I, those with normal
      BMI taking tibolone; II, those with a raised BMI taking tibolone, and III, a
      group with raised BMI not taking tibolone. Blood samples were drawn before and 1,
      2, 6, 9 and 12 months after the initiation of tibolone or, in group III, after
      the start of the study. RESULTS: Serum leptin concentrations were high in all
      women with abnormal BMI. Long-term tibolone administration did not have any
      significant effect on serum leptin concentrations. There was no correlation
      between serum leptin levels and the age and the duration of post-menopausal
      period. There was a high positive correlation between serum leptin levels and BMI
      values. CONCLUSIONS: BMI values affect serum leptin concentrations but long-term
      tibolone administration does not seem to have any effect on serum leptin levels.

PMID- 11311768
TI  - Prostasome-like granules from the PC-3 prostate cancer cell line increase the
      motility of washed human spermatozoa and adhere to the sperm.
AB  - OBJECTIVE: Prostasome-like granules are present in the PC-3 prostate cancer
      cells. Since the seminal prostasomes are able to promote the forward motility of
      human spermatozoa, we conducted a study to determine whether PC-3 prostasomes
      exerted effects similar to those of seminal prostasomes on buffer-washed
      spermatozoa from normospermic semen samples. STUDY DESIGN: We used computer
      assisted sperm analysis (CASA) and immunostaining of prostasomes to find out
      where these granules are located on the spermatozoa. RESULTS: Addition of PC-3
      prostasomes increased the proportion of motile spermatozoa from 12-15% to 50-70%
      (p<0.001). The optimal protein concentration of these prostasomes was 0.1mg/ml.
      Heat treatment of PC-3 prostasomes did not decrease their motility-promoting
      effect. Immunostaining with anti-prostasome monoclonal antibody (mAb78) revealed
      that the PC-3 prostasomes and seminal prostasomes adhered to the sperm cells. The
      staining, which occurred all over the spermatozoa, was intense on the mid-pieces
      and weaker on the sperm heads. Herewith, some prostasome component may activate
      the spermatic mitochondrial function, thus increasing sperm motility. CONCLUSION:
      It is concluded that PC-3 prostasomes bear a functional resemblance to seminal
      prostasomes as regards sperm motility promotion.

PMID- 11311769
TI  - Luteal phase hormonal profile in prediction of pregnancy outcome after assisted
      reproduction.
AB  - The clinical efficacy of luteal phase hormones including estradiol and
      progesterone in the prediction of pregnancy and its outcome in ICSI-ET cycles was
      evaluated. In 121 ICSI-ET cycles, serial estradiol and progesterone levels were
      measured in the luteal phase. The day of ovum pick-up was designated as day 0.
      All the patients had luteal support with vaginal progesterone suppositories after
      embryo transfer (ET). Serial estradiol measurements were performed on days 8, 11
      and 13 and progesterone level on day 11. A single dose of hCG was given for
      corpus luteum rescue 5000 IU, if day 8 estradiol level <200pg/ml; 2000IU, if
      estradiol between 200 and 800pg/ml; no hCG if estradiol level >800pg/ml). On day
      15, beta-hCG level was measured to detect pregnancy and if positive, injected on
      day 17. Fifty-seven pregnancies were achieved in 121 cases after ET (47%).
      Clinical pregnancy rate and ongoing pregnancy rate per ET were 37.1 and 30%,
      respectively. While there was no difference between progesterone levels measured
      on day 11, estradiol levels on days 11 and 13 were significantly higher in women
      who became pregnant. In 40 patients taking only progesterone and in 81 cases
      taking hCG plus progesterone, estradiol levels on days 11 and 13 were
      significantly higher in women who became pregnant. Progesterone levels on day 11,
      in progesterone treated groups, did not differ between pregnant and non-pregnant
      patients. Estradiol and progesterone levels on day 11 and estradiol levels on day
      13 showed a big overlap between pregnant and non-pregnant patients. The efficacy
      of serial testing was evaluated. An increase in estradiol level from day 11 to 13
      was associated with 71% pregnancy rate (72% ongoing). In the case of a decrease
      in estradiol level, the pregnancy rate was 18% of which 80% had to implant.
      Rising estradiol in the late luteal phase is associated with higher pregnancy
      rate and more successful pregnancy outcome.

PMID- 11311770
TI  - The presence and extent of endometriosis do not effect clinical pregnancy and
      implantation rates in patients undergoing intracytoplasmic sperm injection.
AB  - OBJECTIVE: To assess the impact of endometriosis on the outcome of
      intracytoplasmic sperm injection (ICSI) outcome. STUDY DESIGN: Retrospective case
      control study which enrolled 1280 consecutive cycles of 834 couples of ICSI with
      ejaculated sperm. Among them, 973 cycles of 632 couples had resulted in embryo
      transfer (ET). The presence of endometriosis was noted in 110 consecutive cycles
      of 45 patients among which 78 cycles of 44 patients had resulted in ET. Data from
      endometriosis group were analyzed in subgroups of minimal-mild (49 ET cycles of
      25 patients) and moderate-severe (29 ET cycles of 19 patients). The controls
      consisted of 1170 consecutive cycles of age-matched 771 couples. Of the controls,
      588 couples had 895 cycles of ET. Main outcome measures were implantation and
      clinical pregnancy rates. RESULTS: There were no differences in cycle and ET
      cancellation rates between control and endometriosis groups. The number of
      oocytes retrieved, fertilization and cleavage rates and the number and quality of
      embryos developed and transferred were similar among the groups. The implantation
      and clinical pregnancy rates were also comparable. CONCLUSION: The presence and
      extent of endometriosis do not affect implantation and clinical pregnancy rates
      in patients undergoing ICSI.

PMID- 11311771
TI  - Atypical squamous cells of undetermined significance. Clinical experience in a
      Turkish university hospital.
AB  - OBJECTIVE: To assess the significance of atypical squamous cells of undetermined
      significance (ASCUS) in predicting the presence of underlying squamous
      intraepithelial lesion (SIL) of the uterine cervix, and to determine the best
      follow-up method for these patients. STUDY DESIGN: We reviewed 76 cases with
      cervical smears that had been labeled ASCUS over a 41-month period, 64 of which
      were also examined colposcopically. RESULTS: The 76 reported ASCUS cases
      represented 1.2% of all gynecologic cases diagnosed at our center during the same
      time period. Of the 64 patients who underwent colposcopy, 9 (14%) had low-grade
      SIL and 7 (11%) had high-grade SIL. CONCLUSION: Based on this study, ASCUS on a
      cervical smear is a good marker for detecting underlying SIL, and immediate
      colposcopy and directed biopsy are the most appropriate follow-up procedures.

PMID- 11311772
TI  - Glyceryl trinitrate ointment as a potential treatment for primary vaginismus.
AB  - A Muslim Bedouin couple presented with difficulty in engaging in sexual
      intercourse, because of primary vaginismus. The couple rejected behavioral
      cognitive therapy on ethnic. Topical application of nitroglycerin ointment to the
      vagina enabled the couple to enjoy a satisfactory sexual relationship.

PMID- 11311773
TI  - Trophoblastic peritoneal implants after laparoscopic treatment of ectopic
      pregnancy.
AB  - Persistent trophoblastic activity after salpingostomy for ectopic pregnancy
      implies the presence of intra-abdominal trophoblastic tissue, usually within the
      fallopian tube. We report a case of disseminated trophoblastic peritoneal
      implants, presenting as hemoperitoneum three weeks after laparoscopic
      salpingectomy. Only 23 such cases have been reported. Surgical treatment of
      ectopic pregnancy, especially by the laparoscopic technique, may cause
      intraperitoneal spread and reimplantation of trophoblastic tissue. Precautions
      for minimizing this complication are discussed.

PMID- 11311774
TI  - Gestational choriocarcinoma arising in a cornual pregnancy.
AB  - A of a case of cornual pregnancy associated with initial transformation to
      choriocarcinoma is reported. Appropriate monitoring of HCG titers following
      conservative management of ectopic pregnancy is important not only to diagnose
      persistent ectopic gestation, but to avoid missing trophoblastic disease, albeit
      rarely.

PMID- 11311775
TI  - Nitroimidazole-resistant vaginal trichomoniasis treated with paromomycin.
AB  - A 33-year old woman with nitroimidazole-resistant vaginal trichomoniasis is
      described. She was treated with intravaginal paromomycin (500 mg daily for 2
      days). This cured the trichomoniasis but resulted in severe local side effects.
      Paromomycin may be useful for difficult cases of nitroimidazole-resistant
      Trichomonas vaginalis vaginitis. The exact dosage still has to be determined.

PMID- 11311776
TI  - Delayed interval delivery of a second twin.
AB  - We report a case of diamniotic dichorionic pregnancy at 21 weeks and 5 days of
      gestation with threatened preterm labor with cervical modification and protrusion
      into vagina of the amniotic sac of twin one. After 4 days there was a rupture of
      membrane of the protruding sac and delivery of the first twin. We decided to
      retain the other one to allow improvement in the outcome for the second twin. The
      patient was treated with tocolytics, antibiotics and continuously monitored.
      After 18 days there was increasing uterine contractility and we decided to
      perform the cesarean section and delivered the second twin.

PMID- 11311777
TI  - The responses to repeated vibroacoustic stimulation in a fetus with trisomy 18.
AB  - Observation of the fetal movement and fetal heart rate responses to repeated
      vibroacoustic stimulation might be useful as a measure to assess fetal well
      being. Studies of abnormal fetuses are needed to gain insight in the spectrum of
      possible responses to stimulation. We present a case of a fetus with trisomy 18
      that failed to respond to repeated stimulation.

PMID- 11311778
TI  - Occlusion of the ulnar artery in a patient with severe ovarian hyperstimulation
      syndrome.
AB  - A patient with ovarian hyperstimulation syndrome, without additional predisposing
      risk factors for thrombosis suffered thrombotic occlusion of the distal left
      ulnar artery. Treatment with therapeutic heparinization was successful.

PMID- 11311779
TI  - Neuroendocrine small-cell cervical carcinoma.

PMID- 11311780
TI  - Ureterovaginal fistulas complicating laparoscopic hysterectomy: a report of two
      cases.
AB  - Three ureterovaginal fistulas occurred following laparoscopic hysterectomy in two
      patients. Inadvertent burn of the distal ureter by a unipolar electrocautery was
      thought to be the cause. Avoidance of unipolar cautery to achieve hemostasis of
      uterine arteries would have prevented these urologic complications.

PMID- 11311782
TI  - Alzheimer's disease presenilin-1 expression modulates the assembly of
      neurofilaments.
AB  - Mutations in presenilin-1 gene are responsible for the majority of early-onset
      familial Alzheimer's disease cases. The function of this protein and the
      mechanism underlying the pathogenicity of its mutations are still unclear. To
      elucidate the role of presenilin-1 in the Alzheimer's disease pathology, we
      tested two such mutations (P117L and M146L) for their effect in stably
      transfected mouse neuroblastoma cell lines. Over-expression of the wild-type
      presenilin-1 gene induced formation of a well-extended, orderly organized network
      consisting of neurofilaments assembled from the L and H subunits, while in cells
      with the mutant gene this network was markedly reduced to short filaments
      concentrated in structures resembling cups. Cells expressing the mutant gene
      displayed altered processing of the transgene protein and neurofilament-H,
      suggesting that presenilin-1 is the mediator of changes targeted at
      neurofilaments. The two different mutations produced similar alterations,
      implying that this is a common pathogenic mechanism. Presenilin-1, neurofilament
      H and tau proteins showed co-localization as evidenced by confocal microscopy,
      suggesting a possible physiological connection between these three proteins.
      Presenilin-1 appears to influence assembly of the H subunit into neurofilaments
      and the subsequent formation of new neurites. Mutations impair this function of
      presenilin-1, resulting in inhibition of neurite outgrowth. That presenilin-1
      influences the assembly of neurofilaments may represent a novel pathway through
      which presenilin-1 mutations are involved in Alzheimer's disease pathology. In
      this hypothesis, presenilin-1 mutations will be associated with aberrant
      sprouting leading to synaptic loss, a key neuropathological feature of
      Alzheimer's disease.

PMID- 11311783
TI  - Studies on [3H]CP-55940 binding in the human central nervous system: regional
      specific changes in density of cannabinoid-1 receptors associated with
      schizophrenia and cannabis use.
AB  - A number of studies suggested that cannabis use can cause or exacerbate psychoses
      and may increase the risk of developing schizophrenia. These findings suggest
      that changes in the cannabinoid system of the brain may be involved in the
      pathology of schizophrenia. To determine whether changes in the cannabinoid
      system were present in the brains of subjects with schizophrenia, we used in situ
      radioligand binding and autoradiography to measure the binding of [3H]CP-55940 to
      the cannabinoid-1 receptor in the dorsolateral prefrontal cortex (Brodmann's area
      9), caudate-putamen and areas of the temporal lobe from schizophrenic and control
      subjects, some of whom had ingested cannabis close to death. There was an
      increase in the density of [3H]CP-55940 binding to cannabinoid-1 receptors in the
      dorsolateral prefrontal cortex from subjects with schizophrenia (mean+/-S.E.M.:
      142+/-9.9 vs 119+/-6.6fmol/mg estimated tissue equivalents; P<0.05) that was
      independent of recent cannabis ingestion. There was an increase in the density of
      cannabinoid-1 receptors in the caudate-putamen from subjects who had recently
      ingested cannabis (151+/-9.0 vs 123+/-7.2fmol/mg estimated tissue equivalents;
      P<0.05) that was independent of diagnoses. These data indicate that there are
      changes in cannabinoid-1 receptors in the dorsolateral prefrontal cortex that may
      prove to be associated with the pathology of schizophrenia. By contrast, changes
      in the density of cannabinoid-1 receptors may occur in the caudate-putamen in
      response to cannabis ingestion.

PMID- 11311784
TI  - Changes in neuronal excitability and synaptic function in a chronic model of
      temporal lobe epilepsy.
AB  - Long-term potentiation and depression of glutamatergic synaptic responses are
      accompanied by an increased firing probability of neurons in response to a given
      excitatory input. This property, named excitatory postsynaptic potential/spike
      potentiation, has also been described in epileptic tissue and has pro-epileptic
      consequences. In this study, we show that excitatory postsynaptic potential/spike
      potentiation can be reversed in the kainic acid lesioned rat hippocampus, a
      chronic model of temporal lobe epilepsy. Simultaneous in vitro extracellular
      recordings in stratum radiatum and stratum pyramidale were performed in the CA1
      area of the kainic acid lesioned rat hippocampal slices. Fifteen minutes,
      application of the K(+) channel blocker tetraethylammonium resulted in excitatory
      postsynaptic potential/spike potentiation (measured 90min after the start of the
      washout period) which could be reversed by subsequent low-frequency or tetanic
      stimuli. Excitatory postsynaptic potential/spike potentiation and its subsequent
      reversal by an electrical conditioning stimulus were found to have a N-methyl-D
      aspartate receptor-independent component. Tetraethylammonium treatment also
      resulted in excitatory postsynaptic potential/spike potentiation of
      pharmacologically isolated N-methyl-D-aspartate receptor-mediated responses which
      could be reversed by subsequent low-frequency or tetanic stimuli. We conclude
      that excitatory postsynaptic potential/spike potentiation can be reversed in
      epileptic tissue, even in the absence of synaptic plasticity. These results
      suggest the presence of endogenous regulatory mechanisms which are able to
      decrease cell excitability.

PMID- 11311785
TI  - Involvement of dopamine D(2) receptors in complex maze learning and acetylcholine
      release in ventral hippocampus of rats.
AB  - In the current study we focus on the involvement of dopamine D(2) receptors in
      the ventral hippocampus in memory performance and acetylcholine release. Using
      the aversively motivated 14-unit T-maze (Stone maze) the injection of raclopride,
      a D(2) receptor antagonist, into the ventral hippocampus (8 microg/kg) was found
      to impair memory performance. Co-injection of quinpirole, a D(2) receptor agonist
      (8 microg/kg), overcame the impairment in performance. Microdialysis study
      revealed that quinpirole infusion (10-500 microM) into the ventral hippocampus
      stimulated acetylcholine release in a dose-dependent manner, and systemic
      injection of quinpirole (0.5 mg/kg, i.p.) also stimulated acetylcholine release
      in the ventral hippocampus. Infusion of eticlopride, another D(2) receptor
      antagonist, into the ventral hippocampus suppressed acetylcholine release in the
      hippocampus induced by systemic injection of quinpirole. Taken together, we
      suggest that D(2) receptors in the ventral hippocampus are involved in memory
      performance, possibly through the regulation of acetylcholine.

PMID- 11311786
TI  - Unsupervised learning of granule cell sparse codes enhances cerebellar adaptive
      control.
AB  - Marr [J. Physiol. (1969) 202, 437-470] and Albus [Math. Biosci. (1971) 10, 25-61]
      hypothesized that cerebellar learning is facilitated by a granule cell sparse
      code, i.e. a neural code in which the fraction of active neurons is low at any
      one time. In this paper, we re-examine this hypothesis in light of recent
      experimental and theoretical findings. We argue that cerebellar motor learning is
      enhanced by a sparse code that simultaneously maximizes information transfer
      between mossy fibers and granule cells, minimizes redundancies between granule
      cell discharges, and re-codes the mossy fiber inputs with an adaptive resolution
      such that inputs corresponding to large errors are finely encoded. We then
      propose that a set of biologically plausible unsupervised learning rules can
      produce such a code. To maintain a low mean firing rate compatible with a sparse
      code, an activity-dependent homeostatic mechanism sets the cells' thresholds.
      Then, to maximize information transfer, the mossy fiber--granule cell synapses
      are adjusted by a Hebbian rule. Furthermore, to minimize redundancies between
      granule cell discharges, the inhibitory Golgi cell--granule cell synapses are
      tuned by an anti-Hebbian rule. Finally, to allow adaptive resolution, a
      performance-based neuromodulator-like signal gates these three plastic processes.
      We integrate these gated learning rules into a simplified model of the cerebellum
      for arm movement control, and show that unsupervised learning of granule cell
      sparse codes greatly improves cerebellar adaptive motor control in comparison to
      a "fixed" Marr--Albus-type model. Until recently, activity-dependent cerebellar
      plasticity was thought to be largely confined to the granule cell--Purkinje cell
      synapses. This static view of the cerebellum is, however, quickly being replaced
      by an extremely dynamic view in which plasticity is omnipresent. The present
      theoretical study shows how several forms of plasticity in the granular layer of
      the cerebellum can produce fast, accurate and stable cerebellar learning.

PMID- 11311787
TI  - Progressive visual sensitivity loss in the Royal College of Surgeons rat:
      perimetric study in the superior colliculus.
AB  - The Royal College of Surgeons rat has a retinal pigment epithelial cell defect
      which causes a progressive loss of rods occurring primarily over the first few
      months of life. We have studied the consequences of this degenerative process on
      visual sensitivity across the visual field. Sensitivities were determined in the
      superior colliculus for unit responses recorded from 22 days up to one year of
      age from sites encompassing the whole visual field representation. Following
      visual sensitivity assessment, retinae were examined anatomically at the light
      and electron microscopic level. At 22 days of age, sensitivities in dystrophic
      rats were comparable to those of non-dystrophics at any age (40+/-1 and 41+/-1dB,
      respectively), despite the fact that signs of degenerative events were clear at
      the electron microscopic level, including presence of pyknotic photoreceptor
      nuclei, disorganised outer segments and accumulation of debris. However, loss in
      sensitivity was first detected only at 28-36 days of age (27+/-4dB). From then
      on, sensitivities progressively decreased to reach a plateau by 180-240 days (4+/
      2dB). Starting around 90 days and onward, there was a positive gradient of
      sensitivities from temporal to nasal field. Drops in visual sensitivity were
      parallelled by several changes in visual response properties, including prolonged
      latency, inconsistent responsiveness, appearance of bursting spontaneous activity
      and activation of units by stimuli presented outside their classical receptive
      fields. The measure of visual sensitivities by recording visual responses at
      specific sites in the superior colliculus provides a reliable point-to-point
      assessment of retinal function comparable to visual perimetry testing in humans.
      This experimental approach provides the background for answering questions
      arising during the development of potential experimental therapies for retinal
      degeneration using animal models like the Royal College of Surgeons rat.

PMID- 11311788
TI  - Modeling functions of striatal dopamine modulation in learning and planning.
AB  - The activity of midbrain dopamine neurons is strikingly similar to the reward
      prediction error of temporal difference reinforcement learning models.
      Experimental evidence and simulation studies suggest that dopamine neuron
      activity serves as an effective reinforcement signal for learning of sensorimotor
      associations in striatal matrisomes. In the current study, we simulate dopamine
      neuron activity with the extended temporal difference model of Pavlovian learning
      and examine the influences of this signal on medium spiny neurons in striatal
      matrisomes. The modeled influences include transient membrane effects of dopamine
      D(1) receptor activation, dopamine-dependent long-term adaptations of
      corticostriatal transmission, and effects of dopamine on rhythmic fluctuations of
      the membrane potential between an elevated "up-state" and a hyperpolarized "down
      state". The most dominant activity in the striatal matrisomes is assumed to
      elicit behaviors via projections from the basal ganglia to the thalamus and the
      cortex. This "standard model" performs successfully when tested for sensorimotor
      learning and goal-directed behavior (planning). To investigate the contributions
      of our model assumptions to learning and planning, we test the performance of
      several model variants that lack one of these mechanisms. These simulations show
      that the adaptation of the dopamine-like signal is necessary for sensorimotor
      learning and planning. Sensorimotor learning requires dopamine-dependent long
      term adaptation of corticostriatal transmission. Lack of dopamine-like novelty
      responses decreases the number of exploratory acts, which impairs planning
      capabilities. The model loses its planning capabilities if the dopamine-like
      signal is simulated with the original temporal difference model, because the
      original temporal difference model does not form novel associative chains.
      Transient membrane effects of the dopamine-like signal on striatal firing
      substantially shorten the reaction time in the planning task. The capability for
      planning is improved by influences of dopamine on the durations of membrane
      potential fluctuations and by manipulations that prolong the reaction time of the
      model. These results suggest that responses of dopamine neurons to conditioned
      stimuli contribute to sensorimotor reward learning, novelty responses of dopamine
      neurons stimulate exploration, and transient dopamine membrane effects are
      important for planning.

PMID- 11311789
TI  - Identification of the source of the bilateral projection system from cortex to
      somatosensory neostriatum and an exploration of its physiological actions.
AB  - Microinjections of cholera toxin B subunit were made into the area of the
      neostriatum that receives input from the primary somatosensory barrel cortex (SI)
      in the rat. Studies of the cortices then allowed retrograde identification of the
      cortical cells supplying the striatal input. When injections were restricted to
      the neostriatum, retrograde labelling was found in layer V of both SI cortices.
      Ipsilateral to the injection, cells were retrogradely filled with toxin in all
      parts of the barrel field, in adjacent parietal cortex, in the motor cortex and
      in prefrontal areas. A similar distribution across cortical areas was seen
      contralaterally; however, the stained cells in the SI were between rather than
      within barrel columns. An earlier anterograde study suggested two inputs from the
      SI to the neostriatum. The present results indicate that one input to the
      somatosensory area of the neostriatum arises bilaterally from neurons between the
      barrels of the SI, while the topographic pathway from below the barrels is
      present only ipsilaterally. These anatomical results indicate that separate
      stimulation of the two corticostriatal pathways from the barrel cortex is
      possible. Electrical stimulation of the contralateral cortex will activate the
      bilateral pathway, while electrical stimulation of the whisker pads activates the
      barrels and hence the topographic pathway. Neurons in the somatosensory region of
      the striatum responded to stimuli in the contralateral cortex and in the
      contralateral whisker pad. In spite of very different path lengths, stimuli via
      the two routes gave rise to excitatory postsynaptic potentials in the striatal
      cells with similar latencies. The excitatory postsynaptic potentials to whisker
      pad stimulation had a rapid rise time and usually resulted in at least one action
      potential. Responses to stimulation of the contralateral cortex rose to a peak
      more slowly and were more variable in latency, but also gave rise to an action
      potential in the majority of cases. All the neurons had the physiological
      characteristics of medium-sized densely spiny cells and after intracellular
      filling with biocytin had the appropriate morphology. In summary, we propose that
      two corticostriatal pathways arise from layer V cells in the barrel area of the
      somatosensory cortex; one is bilateral and arises from cells mainly below the
      septa, while a topographical pathway arises from cells below the barrels. Both
      pathways can raise the spiny output cells of the striatum to firing threshold.
      The latencies from the contralateral cortex imply slowly conducting fibres with
      considerably more temporal dispersion than the pathway from below the barrels,
      which we excited from the contralateral periphery.

PMID- 11311790
TI  - Development of striatal patch/matrix organization in organotypic co-cultures of
      perinatal striatum, cortex and substantia nigra.
AB  - Organotypic cultures of fetal or early postnatal striatum were used to assess
      striatal patch formation and maintenance in the presence or absence of
      dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum
      prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in
      static culture on clear membrane inserts in Dulbecco's modified Eagle's
      medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day
      12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex,
      which produced a dense dopaminergic innervation and a modest cortical
      innervation. Donors of striatal and cortical tissue were previously injected with
      bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal
      neurons destined to populate the patch compartment of the striatum. Patches of
      BrdU-immunoreactive cells were maintained in organotypic cultures of late
      prenatal (embryonic days 20-22) or early postnatal striatum in the absence of
      nigral dopaminergic or cortical glutamatergic influences. In slices taken from
      embryonic day 19 fetuses prior to the time of in vivo patch formation, patches
      were observed to form after 10 days in vitro, in 39% of nigral-striatal co
      cultures compared to 6% of striatal slices cultured alone or in the presence of
      cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase
      immunoreactivity, were observed in the majority of nigral-striatal co-cultures.
      Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch
      distribution in nearly all cultures, which developed in embryonic day 19 cultures
      after at least six days in vitro. These findings indicate that striatal
      patch/matrix organization is maintained in organotypic culture, and can be
      induced to form in vitro in striatal slices removed from fetuses prior to the
      time of in vivo patch formation. Furthermore, dopaminergic innervation from co
      cultured pieces of ventral mesencephalon enhances patch formation in organotypic
      cultures.

PMID- 11311791
TI  - m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat substantia
      nigra and ventral tegmental area by activating serotonin-2C receptors.
AB  - In vivo electrophysiological techniques were used to study the effect of m
      chlorophenylpiperazine, a non-selective serotonin-2C receptor agonist, on the
      activity of non-dopaminergic neurons in the substantia nigra pars reticulata and
      the ventral tegmental area of anesthetized rats. Intravenous administration of m
      chlorophenylpiperazine (5-320 microg/kg) caused a dose-dependent increase in the
      basal firing rate of a subpopulation of nigral neurons which do not respond to a
      footpinch stimulus [P(0) neurons], whereas it did not affect the activity of
      neurons which are responsive to the footpinch [P(+) neurons]. However, m
      chlorophenylpiperazine (5-320 microg/kg) excited all non-dopaminergic neurons
      sampled in the ventral tegmental area. Moreover, microiontophoretic application
      of m-chlorophenylpiperazine (10-40 nA) caused an excitation of P(0) nigral and
      ventral tegmental area neurons. Pretreatment with the selective serotonin-2C
      receptor antagonist SB 242084 (200 microg/kg, i.v.) completely blocked the
      excitatory effect of i.v. m-chlorophenylpiperazine (5-320 microg/kg), both in the
      substantia nigra pars reticulata and in the ventral tegmental area. It is
      concluded that stimulation of serotonin-2C receptors by m-chlorophenylpiperazine
      activates non-dopaminergic (presumably GABA-containing) neurons in the substantia
      nigra pars reticulata and ventral tegmental area.

PMID- 11311792
TI  - Pallidal border cells: an anatomical and electrophysiological study in the 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkey.
AB  - A dopamine transporter-radioligand binding study demonstrated a dopaminergic
      innervation around the pallidal complex in the normal monkey (n=5), i.e. where a
      subpopulation of pallidal neurons known as "border cells" is classically
      identified. Surprisingly, this peripallidal binding persists in monkeys rendered
      parkinsonian (n=5) with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment.
      The border cell electrophysiological activity was then analysed in normal and
      parkinsonian monkeys (n=2), either in the untreated state or following
      administration of levodopa. Pallidal border cell firing frequency was
      significantly decreased after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      treatment (8.9+/-0.7 vs 31.4+/-1.6Hz, P<0.05). This decrease was partly corrected
      by levodopa administration (19.2+/-1.0Hz, P<0.05 vs both normal and parkinsonian
      situations). The peripallidal dopaminergic innervation suggests that pallidal
      border cells are under a direct dopaminergic control, arising from the ventral
      tegmental area and/or the basal forebrain magnocellular complex, the role of
      which remains unknown. Moreover, the relative sparing of these dopaminergic
      fibers in parkinsonian monkeys suggests that they would exhibit specific adaptive
      properties totally different from those described in the nigrostriatal pathway.

PMID- 11311793
TI  - Inhibition of 6-hydroxydopamine-induced p53 expression and survival of
      neuroblastoma cells following interaction with astrocytes.
AB  - The neurotoxin 6-hydroxydopamine has been used to induce selective dopaminergic
      cell death in animal models of Parkinson's disease. The response of neurons to
      this toxin has been shown to be greatly influenced by astrocytes. Our laboratory
      reported previously that human neuroblastoma SH-SY5Y cells became more resistant
      to the toxicity of 6-hydroxydopamine when co-cultured with mouse astrocytes. This
      enhanced tolerance required direct and specific adhesion between SH-SY5Y cells
      and astrocytes. We hypothesized that this interaction led to biochemical changes
      in SH-SY5Y cells, thereby protecting these cells from toxicity. To study these
      changes, we again co-cultured SH-SY5Y cells with astrocytes and treated them with
      6-hydroxydopamine. An optimized condition of trypsin treatment was employed to
      separate SH-SY5Y cells from astrocytes quickly. Western blot analysis
      demonstrated that 6-hydroxydopamine significantly increased p53 protein in
      monolayer SH-SY5Y cells grown in either regular medium or conditioned medium from
      astrocytes. This change, however, was not observed in the group co-cultured with
      astrocytes. Data obtained from the ribonuclease protection assay indicated that
      similar changes also occurred at the transcriptional level. The enhanced
      resistance of the co-cultured SH-SY5Y cells to the toxicity of 6-hydroxydopamine
      is attributed to the ability of astrocytes to prevent the increase of p53 induced
      by this toxin. This study demonstrates the significance of the interaction
      between astrocytes and neurons when they are exposed to neurotoxins.

PMID- 11311794
TI  - The polysialylated neural cell adhesion molecule reaches cell surfaces of
      hypothalamic neurons and astrocytes via the constitutive pathway.
AB  - Understanding how neurons and glia sort and deliver cell adhesion molecules to
      their cell surface should provide important clues as to how such molecules
      participate in dynamic neuronal functions in the developing and adult brain. The
      present study examines translocation of polysialylated neural cell adhesion
      molecule (PSA-NCAM), a negative regulator of cell adhesion, in cells of the rat
      hypothalamo-neurohypophysial system in which it is expressed throughout life and
      which undergo morphological remodelling in response to stimulation. PSA-NCAM
      expression in this system does not vary markedly in relation to different
      conditions of regulated neurosecretion, suggesting that the glycoprotein reaches
      cell surfaces via the constitutive pathway. To study this more directly, we here
      used immunofluorescence for PSA on NCAM in live, unpermeabilized cells to monitor
      PSA-NCAM surface expression in organotypic slice cultures from postnatal rat
      hypothalami. Subsequent immunolabelling for oxytocin confirmed that the cultures
      included magnocellular oxytocinergic neurons displaying many properties of adult
      neurosecretory neurons in situ. In the cultures, immunoreaction for PSA-NCAM was
      visible on the surface of oxytocinergic and non-oxytocinergic axons. This
      reaction disappeared after exposure of the cultures to endoneuraminidase, an
      enzyme which specifically cleaves alpha-2-8-linked PSA from NCAM. PSA-NCAM
      reappeared on axonal surfaces 4h after enzyme washout. Such reexpression was
      visibly not affected by neuronal activity inhibition (blockade of Ca(2+) channels
      with Mn(2+), of Na(+) channels with tetrodotoxin, or of glutamate receptors with
      6-cyano-7-nitroquinoxaline-2,3-dione or D-2-amino-5-phosphonopentanoic acid) or
      facilitation (K(+) depolarization or GABA-A receptor blockade with bicuculline).
      In contrast, PSA-NCAM surface translocation was inhibited reversibly by cooling
      the cultures at 20 degrees C, a procedure which blocks constitutive secretion and
      which resulted in accumulation of PSA-NCAM in the cytoplasm of oxytocinergic and
      non-oxytocinergic neurons. This treatment also revealed PSA-NCAM in the cytoplasm
      of underlying astrocytes. Our observations provide direct evidence that PSA-NCAM
      reaches the cell surface of hypothalamic neurons and astrocytes via the
      constitutive pathway, independently of Ca(2+) entry and enhanced neuronal
      activity. Thus, PSA-NCAM in the hypothalamo-neurohypophysial system would be
      continuously available to permit its cells to undergo remodelling whenever the
      proper stimulus intervenes.

PMID- 11311795
TI  - Fos protein is required for the re-expression of angiotensin II type 1 receptors
      in the nucleus tractus solitarii after baroreceptor activation in the rat.
AB  - We evaluated in Sprague--Dawley rats the hypothesis that Fos protein induced by
      baroreceptor activation in the nucleus tractus solitarii participates in
      transcriptional regulation of the expression of angiotensin receptor genes.
      Reverse transcription-polymerase chain reaction revealed that baroreceptor
      activation elicited by sustained hypertension resulted in a transient decrease in
      angiotensin II subtype 1, but not subtype 2, receptor messenger RNA, in the
      dorsomedial medulla, including the nucleus tractus solitarii. There was
      subsequently a transitory reduction in the pressor response elicited by
      microinjection bilaterally of angiotensin II (40 pmol) into the nucleus tractus
      solitarii, followed by an increase in c-fos messenger RNA and Fos
      immunoreactivity at the same nucleus. Both the re-expression of angiotensin II
      subtype 1 receptor messenger RNA and restoration of pressor response to
      angiotensin II after baroreceptor activation were significantly blunted by
      bilateral application into the nucleus tractus solitarii of an antisense
      oligonucleotide (50 pmol) that targets against the initiation codon of c-fos
      messenger RNA. Control pretreatment with the corresponding sense oligonucleotide
      (50 pmol), or an antisense c-fos oligonucleotide that targets against a different
      portion of the coding sequence of the c-fos messenger RNA (50 pmol), was
      ineffective. At the receptor level, the angiotensin II-induced pressor response
      was antagonized by the subtype 1 receptor antagonist losartan (1.6 nmol), but not
      by the subtype 2 receptor antagonist PD-123319 (1.6 nmol). These findings suggest
      that sustained hypertension down-regulates angiotensin II subtype 1 receptors at
      both messenger RNA and functional expression levels in the nucleus tractus
      solitarii. Furthermore, Fos protein induced in the nucleus tractus solitarii by
      baroreceptor activation may play a permissive role in the transcriptional
      regulation of the re-expression of this subtype of angiotensin receptors.

PMID- 11311796
TI  - Baroreflex inhibition of cardiac sympathetic outflow is attenuated by angiotensin
      II in the nucleus of the solitary tract.
AB  - Homeostatic regulation of arterial pressure is maintained by arterial
      baroreceptors. Activation of these receptors results in an inhibition of
      sympathetic activity to the heart. It is known that angiotensin II in the nucleus
      tractus solitarii attenuates the baroreceptor reflex-evoked vagal bradycardia.
      Here, we determined whether the cardiac sympathetic component of the baroreceptor
      reflex could be modulated by angiotensin II in the nucleus of the solitary tract.
      An in situ, arterially perfused working heart--brainstem preparation of rat was
      employed and the sympathetic inferior cardiac nerve recorded. Increases in
      perfusion pressure caused a reflex bradycardia and inhibition of inferior cardiac
      nerve activity. Microinjection of angiotensin II (500 fmol) in the nucleus of the
      solitary tract attenuated significantly both the reflex bradycardia and
      inhibition of inferior cardiac nerve activity (P<0.01). The latter was reversible
      and sensitive to losartan, an angiotensin II type 1 receptor antagonist. In
      contrast, the peripheral chemoreceptor reflex evoked an increase in inferior
      cardiac nerve activity that was not affected by angiotensin II applied
      exogenously in the nucleus of the solitary tract. We conclude that within the
      nucleus of the solitary tract angiotensin II exerts a powerful and specific
      inhibitory modulation of the baroreceptor reflex control of sympathetic nerve
      activity destined for the heart. We suggest that our data may have clinical
      implications relating to hypertension, a condition when angiotensin II activity
      is heightened in the brain and the efficacy of the baroreflex is reduced.

PMID- 11311797
TI  - Characterization of interleukin-1 receptor antagonist isoform expression in the
      brain of lipopolysaccharide-treated rats.
AB  - The endogenous interleukin-1 receptor antagonist is the natural inhibitor of the
      biological effects of interleukin-1 during inflammation. Interleukin-1 receptor
      antagonist refers to three isoforms: one secreted and two intracellular forms
      (types I and II). The objective of the present study was to investigate the
      expression of interleukin-1 receptor antagonist isoforms in the rat brain in vivo
      in response to an i.p. injection of lipopolysaccharide. The interleukin-1
      receptor antagonist was studied at the messenger and protein levels by reverse
      transcription-polymerase chain reaction and western blot analysis, respectively.
      Interleukin-1 receptor antagonist messenger RNA was constitutively expressed in
      the brain and its expression increased in response to lipopolysaccharide. The
      three interleukin-1 receptor antagonist protein isoforms were up-regulated after
      lipopolysaccharide treatment in a time-dependent manner. Their relative
      expression differed according to the isoform and brain region studied. Double
      immunofluorescence staining revealed interleukin-1 receptor antagonist positive
      neurons and microglia in hippocampus 24h after lipopolysaccharide stimulation.
      These results demonstrate for the first time that brain cells are able to produce
      interleukin-1 receptor antagonist isoforms in response to a peripheral immune
      challenge with a predominance of the secreted over intracellular forms.

PMID- 11311798
TI  - Reduced ethanol withdrawal severity and altered withdrawal-induced c-fos
      expression in various brain regions of mice lacking protein kinase C-epsilon.
AB  - Withdrawal from chronic ethanol consumption can be accompanied by motor seizures,
      which may be a result of altered GABA(A) receptor function. Recently, we have
      generated and characterized mice lacking the epsilon isoform of protein kinase C
      as being supersensitive to the behavioral and biochemical effects of positive
      GABA(A) receptor allosteric modulators, including ethanol. The aim of the present
      study was to determine whether protein kinase C-epsilon null mutant mice display
      altered seizure severity during alcohol withdrawal. In addition, we used c-fos
      immunohistochemistry immediately following seizure assessment to identify
      potential brain regions involved in any observed differences in withdrawal
      severity. Mice were allowed to consume an ethanol-containing or control liquid
      diet as the sole source of food for 14 days. During the 7-h period following
      removal of the diet, both ethanol-fed wild-type and protein kinase C-epsilon null
      mutant mice displayed an overall increase in Handling-Induced Convulsion score
      versus control-fed mice. However, at 6 and 7h following diet removal, the
      Handling-Induced Convulsion score was reduced in ethanol-fed protein kinase C
      epsilon null mutant mice compared to ethanol-fed wild-type mice. Ethanol-fed
      protein kinase C-epsilon null mutant mice also exhibited a decrease in the number
      of Fos-positive cells in the lateral septum, and an increase in the number of Fos
      positive cells in the dentate gyrus, mediodorsal thalamus, paraventricular nuclei
      of the thalamus and hypothalamus, and substantia nigra compared to ethanol-fed
      wild-type mice. These data demonstrate that deletion of protein kinase C-epsilon
      results in diminished progression of ethanol withdrawal-associated seizure
      severity, suggesting that selective pharmacological inhibitors of protein kinase
      C-epsilon may be useful in the treatment of seizures during alcohol withdrawal.
      These data also provide insight into potential brain regions involved in
      generation or suppression of ethanol withdrawal seizures.

PMID- 11311799
TI  - Neurodegeneration in the animal model of Menkes' disease involves Bcl-2-linked
      apoptosis.
AB  - Copper plays a key role in brain development, function and survival. Alteration
      of its homeostasis is suggested to be an aetiological factor in several
      neurodegenerative diseases. However, the molecular mechanisms relating copper to
      neurodegeneration are still unknown. In the present report, using morphological
      analyses of brain sections of mottled/brindled mutant (Mo(br/y)) mice, the animal
      model of the human genetic copper deficiency associated with neurodegeneration
      (Menkes' disease), we demonstrated that a high degree of apoptotic cells is
      present in the neocortex and in the hippocampus. Biochemical characterisation
      revealed decreased levels of copper content and of the activity of the
      mitochondrial copper-dependent enzyme cytochrome c oxidase. Copper, zinc
      superoxide dismutase activity also shows a slight decrease, while no change was
      observed for glutathione content. Lower levels of ATP were also found, indicative
      of a copper-dependent impairment of energy metabolism. Changes appear to be
      specific for the brain, since no alterations in the activity of liver enzymes
      were found, although the level of copper was strongly decreased. We also tested
      biochemical factors involved in cell commitment to apoptosis. The expression of
      the anti-apoptotic protein Bcl-2, which plays a fundamental role in brain
      development and morphogenesis, was dramatically decreased and the levels of
      cytochrome c released from mitochondria into the cytosol were significantly
      increased. On the basis of these findings, we propose that down-regulation of Bcl
      2 can cause neurodegeneration triggered by mitochondrial damage due to copper
      depletion during brain development in Mo(br/y) mice.

PMID- 11311800
TI  - Capsaicin stimulation of the cochlea and electric stimulation of the trigeminal
      ganglion mediate vascular permeability in cochlear and vertebro-basilar arteries:
      a potential cause of inner ear dysfunction in headache.
AB  - Trigeminal neurogenic inflammation is one explanation for the development of
      vascular migraine. The triggers for this inflammation and pain are not well
      understood, but are probably vasoactive components acting on the blood vessel
      wall. Migraine-related inner ear symptoms like phonophobia, tinnitus, fluctuation
      in hearing perception and increased noise sensitivity provide indirect evidence
      that cochlear blood vessels are also affected by basilar artery migraine. The
      purpose of this investigation was to determine if a functional connection exists
      between the cochlea and the basilar artery. Neuronally mediated permeability
      changes in the cochlea and basilar artery were measured by colloidal silver and
      Evans Blue extravasation, following orthodromic and antidromic stimulation of the
      trigeminal ganglion innervating the cochlea. Capsaicin and electrical stimulation
      induced both dose- and time-dependent plasma extravasation of colloidal silver
      and Evans Blue from the basilar artery and anterior inferior cerebellar artery.
      Both orthodromic and antidromic activation of trigeminal sensory fibers also
      induced cochlear vascular permeability changes and significant quantitative
      differences between the treated and control groups in spectrophotometric assays.
      These results characterize a vasoactive connection between the cochlea and
      vertebro-basilar system through the trigeminal sensory neurons. We propose that
      vertigo, tinnitus and hearing deficits associated with basilar migraine could
      arise by excitation of the trigeminal nerve fibers in the cochlea, resulting in
      local plasma extravasation. In addition, cochlear "dysfunction" may also trigger
      basilar and cluster headache by afferent input to the trigeminal system.

PMID- 11311801
TI  - Oligodendroglial apoptosis occurs along degenerating axons and is associated with
      FAS and p75 expression following spinal cord injury in the rat.
AB  - Apoptosis or programmed cell death has been reported after CNS trauma. However,
      the significance of this mechanism in the pathophysiology of spinal cord injury,
      in particular at the cervical level, requires further investigation. In the
      present study, we used the extradural clip compression model in the rat to
      examine the cellular distribution of apoptosis following cervical spinal cord
      injury, the relationship between glial apoptosis and post-traumatic axonal
      degeneration and the possible role of apo[apoptosis]-1, CD95 (FAS) and p75 in
      initiating post-traumatic glial apoptosis. In situ terminal-deoxy-transferase
      mediated dUTP nick end labeling revealed apoptotic cells, largely
      oligodendrocytes as identified by cell specific markers, in grey and white matter
      following spinal cord injury. Apoptotic cell death was confirmed using electron
      microscopy and by the demonstration of DNA laddering on agarose gel
      electrophoresis. Beta-amyloid precursor protein was used as a molecular marker of
      axonal degeneration on western blots and immunohistochemistry. Degeneration of
      axons was temporally and spatially co-localized with glial apoptosis. FAS and p75
      protein expression was seen in astrocytes, oligodendrocytes and microglia, and
      was also seen in some apoptotic glia after cord injury. Both FAS and p75
      increased in expression in a temporal course, which mirrored the development of
      cellular apoptosis. The downstream caspases 3 and 8, which are linked to FAS and
      p75, demonstrated activation at times of maximal apoptosis, while FLIP-L an
      inhibitor of caspase 8, decreased at times of maximal apoptosis. We conclude that
      axonal degeneration after traumatic spinal cord injury is associated with glial,
      in particular oligodendroglial, apoptosis. Activation of the FAS and p75 death
      receptor pathways may be involved in initiating this process.

PMID- 11311802
TI  - Capsaicin-induced depolarisation of mitochondria in dorsal root ganglion neurons
      is enhanced by vanilloid receptors.
AB  - Capsaicin, a pungent ingredient of hot chilli peppers, triggered Ca(2+) influx in
      dorsal root ganglion (DRG) neurons, which express specific vanilloid receptors of
      type 1, with ED(50)<100 nM. An increase in capsaicin concentration to 10 microM
      inhibited Ca(2+) clearance from the cytosol, but did not affect the amplitude of
      intracellular Ca(2+) elevation. In DRG neurons, 10 microM capsaicin also produced
      a significant drop in mitochondrial membrane potential (Deltapsi), as measured
      with the mitochondria-specific potentiometric fluorescent dye JC-1. Similar loss
      of mitochondrial potential upon application of capsaicin was observed in non
      neuronal primary (human lymphocytes) and transformed (human myeloid leukaemia
      cell line, HL-60) cells. The EC(50) values for capsaicin-induced mitochondrial
      depolarisation were 6.9 microM (DRG neurons), 200 microM (human lymphocytes) and
      150 microM (HL-60 cells). Removal of extracellular Ca(2+) or an application of
      the antioxidant trolox attenuated capsaicin-induced dissipation of Deltapsi in
      DRG neurons, but not in human lymphocytes and HL-60 cells. Rotenone, an inhibitor
      of complex I of the mitochondrial respiratory chain, and oligomycin, an inhibitor
      of F(0)F(1)-ATPase, significantly enhanced the mitochondrial depolarisation
      produced by capsaicin in DRG neurons. In human lymphocytes and HL-60 cells, only
      oligomycin potentiated the effect of capsaicin. From our results, we suggest
      that, in DRG neurons and non-neuronal cells, capsaicin dissipates Deltapsi,
      possibly due to a direct inhibition of complex I of the mitochondrial respiratory
      chain. The presence of vanilloid receptor-1 in DRG neurons makes their
      mitochondria 20-30-fold more sensitive to the depolarising effect of capsaicin
      compared with non-neuronal cells lacking vanilloid receptor-1. The higher
      sensitivity of DRG neurons to capsaicin may underlie a selective neurotoxicity of
      capsaicin towards sensory neurons.

PMID- 11311803
TI  - Stimulation of mouse cultured sympathetic neurons by uracil but not adenine
      nucleotides.
AB  - Cultured neurons from the paravertebral sympathetic chain of rats possess
      excitatory P2X as well as excitatory uracil nucleotide-sensitive P2Y receptors.
      Preliminary observations had indicated that the analogous neurons of mice lacked
      P2X receptors. This difference was now investigated. Thoracolumbar sympathetic
      neurons from one- to three-day-old mice were cultured for seven days. When the
      neurons were preincubated with [3H]noradrenaline and then superfused, ATP failed
      to cause any change in tritium outflow. UTP (3-300 microM) and UDP (30-100
      microM), in contrast, caused marked increases, and so did nicotine (3-100
      microM). The effect of UTP was not changed by suramin but abolished by
      tetrodotoxin and in the absence of calcium. The effect of nicotine was
      antagonized by hexamethonium and also abolished by tetrodotoxin and in the
      absence of calcium. Pre-exposure to UDP prevented the effect of UTP. In neurons
      studied by means of whole-cell patch-clamp techniques under current clamp, ATP
      lacked any effect. UTP (100 microM), UDP (100 microM) and nicotine (10 microM)
      caused depolarization accompanied by action potentials. Pre-exposure to UDP
      prevented the effect of UTP. In neurons studied under voltage clamp, ATP, UTP and
      UDP failed to cause any detectable current. Nicotine (10 microM), in contrast,
      elicited inward currents. Neither UTP nor UDP reduced the M-type potassium
      outward current. These results demonstrate a pronounced difference between
      cultured sympathetic neurons from the mouse and the rat paravertebral chain.
      Neurons from both species possess the nicotinic acetylcholine receptor. Neurons
      from both species also possess uracil nucleotide-sensitive P2Y receptors which,
      when activated, mediate depolarization, action potential firing and noradrenaline
      release; these effects are not due to inhibition of M-type potassium channels.
      Only the rat but not the mouse neurons, however, possess P2X receptors which,
      when activated, mediate cation entry, depolarization, action potential generation
      and transmitter release. The absence of functional P2X receptors makes the mouse
      neurons suitable for further study of the uracil nucleotide-sensitive P2Y
      receptors.

PMID- 11311804
TI  - Sympathetic hyperinnervation of the uterus in the estrogen receptor alpha knock
      out mouse.
AB  - Uterine innervation undergoes cyclical remodeling in the adult virgin rat.
      Previous studies showed that ovariectomy leads to increased uterine sympathetic
      nerve density, and this can be reduced by estrogen administration. However, the
      receptor mechanism by which estrogen modulates sympathetic innervation is
      unknown. The present study assessed the role of the estrogen receptor alpha in
      establishing levels of uterine innervation by comparing the nerve abundance in
      mice with a null mutation of the estrogen receptor alpha with those of the wild
      type cycling mouse. Immunostaining for total uterine innervation using antibodies
      against the pan-neuronal marker protein gene product 9.5 showed that nerve
      numbers in normally cycling wild-type mice were high in diestrus when circulating
      estrogen is at its nadir, and low at estrus, coincident with high plasma
      estrogen. Uteri of the estrogen receptor alpha knock-out mice were smaller than
      those of wild-type mice, but even when corrected for differences in size, total
      innervation was 188% and 355% greater than that of wild-type mice at diestrus and
      estrus, respectively. This hyperinnervation is associated with increased numbers
      of nerves immunoreactive for the noradrenergic enzyme dopamine beta-hydroxylase,
      without obvious differences in those containing calcitonin gene-related peptide
      or the vesicular acetylcholine transporter. While estrogen supplementation of the
      ovariectomized wild-type mice significantly reduced total uterine innervation,
      neither ovariectomy nor estrogen supplementation affected uterine nerve density
      in estrogen receptor alpha knock-out mice.We conclude that estrogen acting
      through the estrogen receptor alpha determines the number of sympathetic nerve
      terminal branches within uterine smooth muscle target. In mice with low
      circulating estrogen, or high estrogen but lacking the functional estrogen
      receptor alpha, the uterus contains abundant sympathetic nerves, whereas estrogen
      acts via the estrogen receptor alpha to regulate uterine innervation by reducing
      numbers of intact sympathetic nerves. Although it is not known whether estrogen
      acts on the target or neuron to initiate these changes, the estrogen receptor
      alpha apparently plays a major role in the cyclical modulation of uterine
      sympathetic innervation.

PMID- 11311805
TI  - Electrophysiological characteristics distinguish three classes of neuron in
      submucosal ganglia of the guinea-pig distal colon.
AB  - Intracellular recordings were made from neurons in the submucosal ganglia of the
      guinea-pig distal colon. The recording electrode contained the intracellular
      marker biocytin, which was injected into neurons so that their
      electrophysiological characteristics could be correlated with their shape.
      Correlations of electrophysiology and shape have not been reported previously for
      neurons in this region. Three types of neuron were identified on
      electrophysiological grounds. Neurons of the first type (S neurons) had
      tetrodotoxin-sensitive soma action potentials, and received fast and slow
      excitatory synaptic inputs. They had uniaxonal morphologies and may function as
      secretomotor or possibly vasomotor neurons. The second type (AH neurons) received
      only slow synaptic input, while the soma action potential had tetrodotoxin
      sensitive and -insensitive components with a shoulder on the falling phase and a
      long-lasting afterhyperpolarisation of the membrane potential following a single
      action potential. Neurons of this type had multipolar morphologies and provided
      dense innervation of adjacent submucosal ganglia. These neurons are similar to
      the submucosal intrinsic primary afferent neurons of the guinea-pig small
      intestine. The final type of neuron [the low-threshold (LT) neuron] had
      electrophysiological characteristics that set it apart from those described
      previously within enteric plexuses. They expressed tetrodotoxin-insensitive
      voltage-gated soma currents, did not have long-lasting afterhyperpolarisations
      and received only slow synaptic input. In addition, these neurons were very
      excitable: they had large input resistances and low thresholds for action
      potential discharge, and often fired action potentials in the absence of
      stimulation. Neurons with these characteristics were uniaxonal and thus are
      likely to be secretomotor or possibly vasomotor neurons. This study has shown
      that submucosal neurons of the distal colon fall into three distinct types, which
      can be distinguished by a combination of electrophysiological and morphological
      criteria.

PMID- 11311806
TI  - Phosphatidylinositol 3-kinase activity in murine motoneuron disease: the
      progressive motor neuropathy mouse.
AB  - A murine model of motoneuron disease, the pmn/pmn mouse, shows a reduction in the
      retrograde transport of fluorescent probes applied directly onto the cut end of
      sciatic nerve. Brain-derived neurotrophic factor (BDNF), when co-applied with
      fluorescent tracers, increases the number of retrograde labelled motoneurons. We
      demonstrate here that spinal cord tissue from pmn/pmn mice had significantly
      reduced phosphatidylinositol 3-kinase activity and expression in the particulate
      fraction compared to controls, without changes in the activities or expression of
      the downstream kinases, protein kinase B/Akt or Erk1. Systemic administration of
      BDNF augmented phosphatidylinositol 3-kinase specific activity in spinal cord
      tissue from pmn/pmn and control mice, with a greater elevation in the particulate
      fractions of pmn/pmn mice than in controls. We examined the effect of inhibitors
      of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase on
      the retrograde labelling of motoneurons, 24h following the direct application of
      inhibitors and Fluorogold to the cut end of sciatic nerve in control and pmn/pmn
      mice (labelling index). The mitogen-activated protein kinase kinase inhibitor PD
      98059 had no effect on the labelling index in control or pmn/pmn mice. In the
      absence of exogenous BDNF, phosphatidylinositol 3-kinase inhibitors reduced the
      number of labelled motoneurons in control mice, without changing the labelling
      index in pmn/pmn. Co-application of phosphatidylinositol 3-kinase inhibitors with
      BDNF to the cut end of sciatic nerve blocked the action of BDNF on retrograde
      labelling in pmn/pmn mice. These results indicate that the retrograde labelling
      of motoneurons is mediated by phosphatidylinositol 3-kinase-dependent and 
      independent pathways. In pmn/pmn mice, phosphatidylinositol 3-kinase activity in
      spinal neurons is below the level required for optimal retrograde labelling of
      motoneurons and labelling can be augmented by the administration of growth
      factors stimulating phosphatidylinositol 3-kinase activity. The data indicate
      that phosphatidylinositol 3-kinase activity is important in the uptake and/or
      retrograde transport of substances by motoneurons and is altered in this model of
      motoneuron diseases.

PMID- 11311807
TI  - Treatment of the neuromuscular junction with 4-aminopyridine results in improved
      reinnervation following nerve injury in neonatal rats.
AB  - During early postnatal development, nerve injury results in the death of a large
      proportion of motoneurones and poor recovery of muscle function. Our previous
      results have shown that premature enhancement of transmitter release from nerve
      terminals prevents the death of motoneurones following neonatal nerve injury.
      Whether this increase in motoneurone survival is reflected in an improvement in
      the reinnervation of muscle was studied here. The muscles in one hindlimb of
      newborn rats were treated with 4-aminopyridine. Three days later, the sciatic
      nerve was crushed in the treated leg. When the animals were seven, 14 and 21days
      of age, the soleus and extensor digitorum longus muscles were removed and
      processed for GAP-43 (a 43-kDa growth-associated protein) and synaptophysin
      immunocytochemistry. Both GAP-43 and synaptophysin were expressed in normal
      soleus and extensor digitorum longus muscles at seven days. Synaptophysin was
      still expressed at 14 days, but GAP-43 expression had declined. Following nerve
      injury at three days of age, there was no GAP-43 or synaptophysin
      immunoreactivity in nerve terminals at seven days. By 21 days, there were 17.3+/
      2.1 GAP-43-positive terminals per section in the soleus and 17.7+/-1.4 in the
      extensor digitorum longus, with mean terminal areas of 47.5+/-3.3 and 49.8+/-2.6
      microm(2), respectively. In animals in which nerve crush was preceded by 4
      aminopyridine treatment, at 21 days there were 32.9+/-2.6 GAP-43-immunoreactive
      terminals in the soleus and 44.9+/-2.3 in the extensor digitorum longus, with a
      mean area of 122.7+/-6.6 microm(2) in the soleus and 136.2+/-9.7 microm(2) in the
      extensor digitorum longus. These results indicate that in muscles pretreated with
      4-aminopyridine, prior to nerve crush at three days, there are significantly more
      terminals, which occupy a larger area than in untreated muscles. Thus, increasing
      transmitter release prior to nerve injury significantly improved the ability of
      axons to reinnervate muscle.

PMID- 11311808
TI  - Spontaneous discharge and response characteristics of central otolith neurons of
      rats during postnatal development.
AB  - To study the developmental profile of otolith-related vestibular nuclear neurons,
      their spontaneous activities and response dynamics were examined in decerebrate
      rats aged seven, 14, 21 and 84 (adult) days. Extracellular recordings were
      performed in the lateral and descending vestibular nucleus of animals held at the
      stationary position in the earth-horizontal or subjected to constant velocity off
      vertical axis rotation, which selectively stimulates the otolith receptors. All
      neurons displayed sinusoidal position-dependent modulation in discharge rate,
      indicating their capability in coding spatial information during low-frequency
      head movement. Some neurons showed a full-cycle response to off-vertical axis
      rotation (non-clipped), while other neurons were silenced in discharge during
      parts of each rotary cycle (clipped). In seven-day-old rats, three-quarters of
      the responsive neurons sampled were clipped and the proportion progressively
      decreased to less than one-quarter in adult rats. In each age group, the clipped
      neurons discharged in approximately 60% of the stimulus cycle. Response gains of
      the neurons increased with age, reaching a plateau from 21 days of age for
      clipped neurons and 14 days for non-clipped neurons. The clipped neurons
      demonstrated higher response gains than the non-clipped neurons at or beyond 21
      days of age. Spontaneous activities of the neurons at the stationary and earth
      horizontal positions were analysed in relation to their response gains; a
      positive correlation was observed from 14 days of age onwards. Both types of
      neurons showed progressive increase in spontaneous activity as the rats matured,
      though the clipped neurons exhibited significantly lower resting rates than the
      non-clipped neurons at each of the age groups studied. Some neurons that
      responded to off-vertical axis rotation were not spontaneously active at the
      stationary position, but the proportion of these decreased significantly with
      age. The coefficient of variation of each age group showed a bimodal
      distribution, thereby allowing spontaneously active neurons to be assigned as
      regular or irregular. Though the vast majority of both the clipped and non
      clipped neurons showed irregular discharge patterns at seven days of age, the
      overall population became more regular as the rats matured. Irregular neurons of
      young rats exhibited phase-stable and phase-shift responses, while those of older
      rats showed only the phase-stable response. This distinction was not observed
      amongst regular neurons over the ages studied. Our results reveal features of
      central otolith neurons that can be taken as signs of maturation during the first
      three postnatal weeks. These neuronal features provide the framework for the
      analysis of behaviours mediated by the otolith system during postnatal
      maturation.

PMID- 11311809
TI  - Target-dependent differentiation and development of molluscan neurons and
      neuroendocrine cells: use of parasitisation as a tool.
AB  - Specimens of the freshwater snail Lymnaea stagnalis infected with the schistosome
      parasite Trichobilharzia ocellata show a strongly inhibited development of their
      reproductive tract. We hypothesised that the effects of the underdevelopment of
      targets are reflected at the level of the neuronal development of (i) the motor
      neurons innervating the male copulation organ and (ii) neuroendocrine cells
      regulating the gonad. We determined the state of neuronal development by
      measuring cell number, cell size and neuropeptide gene expression. Our results
      show that the neuronal development of both copulation controlling anterior lobe
      motor neurons of the right cerebral ganglion and neuroendocrine caudodorsal
      cells, which produce neuropeptides regulating ovulation, egg laying and
      accompanying behaviour, are affected in parasitised animals in which their
      respective target organs were not developed. The cell bodies were smaller and
      fewer cells were found to express neuropeptide genes compared to those in non
      parasitised animals. These effects were not observed in the appropriate controls.
      Backfills and lesions of the penis nerve have shown that the inhibited
      development of central motor neurons in parasitised snails is target dependent;
      neighbouring neurons that have no connection with the male copulation organ are
      not affected. Our data suggest that this effect is established by target-derived
      neurotrophic factors that need this connection for being transported to the
      innervating motor neurons. We propose that the effect on the neuroendocrine
      caudodorsal cells is mediated by a humoral factor, since they have no known
      connection with their target. We have shown that the size and gene expression of
      motor neurons controlling copulation behaviour in the pond snail Lymnaea
      stagnalis are related to the size of their target, the copulation organ, and
      depend on the connection with this target.

PMID- 11311820
TI  - Online reference database of European Y-chromosomal short tandem repeat (STR)
      haplotypes.
AB  - The reference database of highly informative Y-chromosomal short tandem repeat
      (STR) haplotypes (YHRD), available online at http://ystr.charite.de, represents
      the largest collection of male-specific genetic profiles currently available for
      European populations. By September 2000, YHRD contained 4688 9-locus (so-called
      "minimal") haplotypes, 40% of which have been extended further to include two
      additional loci. Establishment of YHRD has been facilitated by the joint efforts
      of 31 forensic and anthropological institutions. All contributing laboratories
      have agreed to standardize their Y-STR haplotyping protocols and to participate
      in a quality assurance exercise prior to the inclusion of any data. In view of
      its collaborative character, and in order to put YHRD to its intended use, viz.
      the support of forensic caseworkers in their routine decision-making process, the
      database has been made publicly available via the Internet in February 2000.
      Online searches for complete or partial Y-STR haplotypes from evidentiary or non
      probative material can be performed on a non-commercial basis, and yield observed
      haplotype counts as well as extrapolated population frequency estimates. In
      addition, the YHRD website provides information about the quality control test,
      genotyping protocols, haplotype formats and informativity, population genetic
      analysis, literature references, and a list of contact addresses of the
      contributing laboratories.

PMID- 11311821
TI  - Forensic evaluation of Y-STR haplotype matches: a comment.

PMID- 11311822
TI  - Mutations at Y-STR loci: implications for paternity testing and forensic
      analysis.
AB  - Knowledge about mutation rates and the mutational process of Y-chromosomal short
      tandem-repeat (STR) or microsatellite loci used in paternity testing and forensic
      analysis is crucial for the correct interpretation of resulting genetic profiles.
      Therefore, we recently analysed a total of 4999 male germline transmissions from
      father/son pairs of confirmed paternity (probability > or = 99.9%) at 15 Y-STR
      loci which are commonly applied to forensics. We identified 14 mutations. Locus
      specific mutation rate estimates varied between 0 and 8.58 x 10(-3), and the
      overall average mutation rate estimate was 2.80 x 10(-3) (95% CIL 1.72 x 10(-3)
      4.27 x 10(-3)). In two confirmed father/son pairs mutation at two Y-STRs were
      observed. The probability of two mutations occurring within the same single
      germline transmission was estimated to be statistically not unexpected.
      Additional alleles caused by insertion polymorphisms have been found at a number
      of Y-STRs and a frequency of 0.12% was estimated for DYS19. The observed
      mutational features for Y-STRs have important consequences for forensic
      applications such as the definition of criteria for exclusions in paternity
      testing and the interpretation of genetic profiles in stain analysis. In order to
      further enrich our knowledge of Y-STR mutations we suggest the establishment of a
      Y-STR mutation database and ask the forensic community for data contribution.

PMID- 11311823
TI  - Application of a Y-STR-pentaplex PCR (DYS19, DYS389I and II, DYS390 and DYS393)
      to sexual assault cases.
AB  - A survey of 89 random rape cases including 166 semen traces, according to the
      prostate-specific-antigen test, showed the need for a more efficient method of
      DNA-profiling. No male autosomal STR-profile could be detected, after
      differential lysis, in 35% of the 84 samples usually containing high amounts of
      the victim's cells, i.e. vaginal/anal washings and knickers. A Y-STR-pentaplex
      was applied to the stored sperm fraction of 50 unsolved semen traces, with
      success in 48% of them. The chance of success depends of the amount of total DNA
      available and of the quality of the extracted DNA.

PMID- 11311824
TI  - DYS STR analysis with epithelial cells in a rape case.
AB  - We report here the application of Y-chromosomal DNA analysis in a rape case,
      which occurred in Stuttgart, Germany. Microscopic examination of the victim's
      vaginal swabs and her underwear showed no sperm cells. DNA was extracted from
      vaginal and epithelial cells and analysed with the autosomal systems SE33, THO1
      (singleplex) and with the multiplex Profiler Plus (Applied Biosystems, Foster
      City, USA). The results of these autosomal STR analysis gave no hint at a mixed
      sample and failed to identify a male profile. DYS STR analysis with the systems
      DYS391, DYS392, DYS393, DYS19 and DYS389 I/II showed the same characteristic
      features as the suspect. We used this incomplete haplotype to search in the Y-STR
      Haplotype Reference Database via Internet. In a Caucasian population sample of
      3589 minimal haplotypes we found 71 matches. The suspect confessed the crime and
      was finally condemned to 4 years imprisonment.

PMID- 11311825
TI  - Routine Y-STR typing in forensic casework.
AB  - In the field of molecular diagnosis, forensic casework analysis is one of the
      most demanding investigations, due to its social impact. Optimization of DNA
      typing multiplex reactions with identical cycling conditions as those required by
      autosomal short tandem repeats (STR) multiplex reduces errors, and saves time and
      reagents. Previously, we validated a five Y-STRs set, all of them generating
      single band patterns. This work reports the optimization of combined multiplexes,
      a triplex (DYS19, DYS390 and DYS391) and a duplex (DYS392 and DYS393), that can
      be amplified in identical cycling conditions as those required by commercially
      available multiplex autosomal STR kits. In addition both Y chromosome multiplexes
      can be combined for co-injection on a capillary electrophoresis based automated
      sequencer. Statistical attributes of the haplotypes of the five Y-STR
      investigated were evaluated in unrelated males from different metropolitan areas
      of Argentina. This system was successfully used for investigating more than 350
      forensic routine cases in our country.

PMID- 11311826
TI  - Examination of Y-STR mutations in sex chromosomal abnormality in forensic cases.
AB  - The Y-STR typing was carried out on eight DNA samples (three from criminal cases)
      demonstrating Klinefelter's syndrome. STR types in the X chromosome were randomly
      distributed. However, some Y-STR markers were distributed within the normal range
      but restricted to only one or two specific alleles, that is, some specific
      haplotypes were found in Klinefelter's syndrome. In addition, a single nucleotide
      polymorphism in DYS390 (transversion of G to A at the 28th position downstream of
      tandem repeats) was detected in Klinefelter samples. This Y-STR polymorphism and
      restricted Y-STR alleles in Klinefelter's syndrome is not known, but it might be
      related to the genesis of Klinefelter's syndrome. We also found that extended
      standard haplotypes of these samples are extremely rare in the normal population,
      according to the Y-STR haplotype reference database (YHRD). The extended standard
      haplotype database in a Japanese population is also reported. In 100 unrelated
      Japanese, 89 haplotypes were observed, and the haplotype diversity was calculated
      to be 0.9866.

PMID- 11311827
TI  - Y-chromosomal STR haplotypes in Pakistani populations.
AB  - 16 Y-specific STR loci have been analysed in 711 males from 12 populations in
      Pakistan. Individual loci showed between 4 and 10 alleles, and diversities ranged
      from 0.07 to 0.77. A total of 527 different haplotypes were found and the
      haplotype diversity ranged from 0.92 to 0.99 for the different populations. 446
      haplotypes occurred in single individuals, and only 19 haplotypes were present in
      more than three males, but two striking examples of haplotype sharing were found,
      one involving 13 individuals, and the other 17. The 13 individuals were all
      Parsis, and 16 of the 17 were Brahuis, providing evidence for population
      substructuring.

PMID- 11311828
TI  - Allele sequences of six new Y-STR loci and haplotypes in the Chinese Han
      population.
AB  - Human chromosome Y-specific short tandem repeat (Y-specific STR) markers have
      useful properties for forensic applications. However, there is a need to develop
      more Y-specific STR markers, because the discriminating power of each STR locus
      is limited. In the present study, we describe our results on six new Y-specific
      STR markers that were initially located using sequence database information by
      Ayub et al. and were named DYS434, DYS435, DYS436, DYS437, DYS438 and DYS439. Our
      studies focused on the analysis of the DNA sequence for each allele at all six Y
      specific STR loci in order to understand their structures in the human genome and
      to construct human allelic ladders, which are necessary for forensic DNA typing.
      In addition, the haplotype distribution for all six analyzed loci was studied in
      a Chinese Han population sample. The results indicate that DYS434, DYS435,
      DYS436, DYS437, DYS438 and DYS439 are useful Y-specific STR markers for forensic
      sciences.

PMID- 11311829
TI  - Population genetics of Y-chromosomal microsatellites in Baltic males.
AB  - Y-chromosomal microsatellites (STRs) are potentially useful in forensic practice
      but, in contrast to autosomal systems, large and diverse population databases are
      required in order to facilitate the statistical evaluation of donor-stain
      matches. Since appropriate data from the Baltic region have so far been lacking,
      blood samples were obtained from 430 males originating from one of the three
      Baltic states and these samples were genotyped using a previously described
      "extended core set" of nine Y-STR marker systems. Allele frequency distributions
      and discrimination indices were calculated, and the three populations were tested
      for genetic differences by means of analysis of molecular variance (AMOVA). A
      larger genetic difference became apparent between Estonian and both Lithuanian
      and Latvian males than between the latter two, non-Finno-Ugric speaking
      populations. The haplotype data reported here have been included into the Y-STR
      database maintained at the Institute of Legal Medicine, Humboldt University,
      Berlin.

PMID- 11311830
TI  - Y-chromosomal SNP haplotype diversity in forensic analysis.
AB  - Many Y-chromosomal single nucleotide polymorphisms (SNPs) are now available. The
      haplogroups which they define are highly non-randomly distributed among
      populations, and could contribute much to population-of-origin prediction from
      DNA. If this potential is to be exploited in forensic analysis, high-throughput,
      parallel methods are required for Y-SNP typing.

PMID- 11311831
TI  - The use of the LightCycler for the detection of Y chromosome SNPs.
AB  - A novel methodology based on PCR monitoring on-line with fluorescent formats
      using the LightCycler for Y chromosome SNP typing is proposed. The main
      advantages of the system are the time necessary for the analysis (which is around
      20 min), the robustness and the accuracy of the method and especially its
      sensitivity, which permits the detection of the male component in male-female
      mixtures up to 1:300 for some of the SNPs. Singleplexes of four different SNPs
      (M9, sY81, SRY-1532 and SRY-2627) as well as two duplexes (M9 and sY81 on the one
      hand and SRY-1532 and SRY-2627 on the other) were efficiently implemented. A
      simultaneous amplification and analysis of the four SNPs is also possible. It
      seems difficult with the current methodology to implement more than a quadruplex.

PMID- 11311832
TI  - The human Y chromosome: function, evolution and disease.
AB  - The human Y chromosome is strictly paternally inherited and, in most of its
      length, does not recombine during male meiosis. These features make the Y a very
      useful genetic marker for different purposes. In the last decade, the Y has been
      increasingly used to investigate the evolution, migrations and range expansions
      of modern humans. The possibility to construct highly informative Y chromosome
      haplotypes has also had a significant impact in forensic studies and paternity
      testing. All these studies assume that the Y chromosome markers used are
      selectively neutral. However, recent experimental and statistical analyses
      suggest that both positive and negative selection are acting on the Y chromosome
      and, consequently, may influence Y chromosome haplotype distribution in the
      general population. Current data suggest that the effects of selection on
      patterns of Y chromosome distribution are minimal, however as interest focuses on
      biological functions of the Y chromosome which have a major impact on male
      fitness such as fertility, these assumptions may be challenged. This review
      briefly describes the genes and biological functions of the human Y chromosome
      and its use in disentangling the origin and history of human populations. An
      overview of the role of selection acting on the Y chromosome from the perspective
      of human population histories and disease is given.

PMID- 11311833
TI  - The European Association for Communication in Healthcare.

PMID- 11311834
TI  - Measuring the involvement of patients in shared decision-making: a systematic
      review of instruments.
AB  - We wanted to determine whether research instruments exist which focus on
      measuring to what extent health professionals involve patients in treatment and
      management decisions. A systematic search and appraisal of the relevant
      literature was conducted by electronic searching techniques, snowball sampling
      and correspondence with field specialists. The instruments had to concentrate on
      assessing patient involvement in decision-making by observation techniques
      (either direct or using audio or videotaped data) and contain assessments of the
      core aspects of 'involvement', namely evidence of patients being involved
      (explicitly or implicitly) in decision-making processes, a portrayal of options
      and a decision-making or deferring stage. Eight instruments met the inclusion
      criteria. But we did not find any instruments that had been specifically designed
      to measure the concept of 'involving patients' in decisions. The results reveal
      that little attention has been given to a detailed assessment of the processes of
      patient involvement in decision-making. The existing instrumentation only
      includes these concepts as sub-units within broader assessments, and does not
      allow the construct of patient involvement to be measured accurately. Instruments
      developed to measure 'patient-centeredness' are unable to provide enough focus on
      'involvement' because of their attempt to cover so many dimensions. The concept
      of patient involvement (shared decision-making; informed collaborative choice) is
      emerging in the literature and requires an accurate method of assessment.

PMID- 11311836
TI  - Knowledge and attitudes of high school pupils towards peers' attention deficit
      and learning disabilities.
AB  - The purpose of this study was to investigate pupils' knowledge and attitudes in
      the areas of attention deficit and hyperactivity (ADHD) and learning disabilities
      (LD). One hundred and four high school pupils in Holon (Israel) were interviewed
      and anonymously completed a questionnaire on these conditions. Pupils' knowledge
      on the topic of ADHD was low (62%); they showed a better knowledge about LD
      (75%). They showed a partially tolerant attitude (62.7%) towards pupils suffering
      from ADHD; on the other hand, they had a somewhat more positive and perceptive
      attitude (74.1%) towards peers diagnosed as learning disabled. Pupils' attitudes
      became more perceptive with increasing age. There was no correlation between
      pupils' knowledge and attitude. Pupils had learned about these two handicapped
      conditions from various sources; TV (66.3%), newspapers (63.5%) and school
      (53.8%), while physicians and nurses occupied the 5th and last place. Information
      about these two disabilities (ADHD and LD) should be added to the curriculum and
      be taught by qualified specialists, as there is an obvious statistically
      deficient knowledge in these areas.

PMID- 11311835
TI  - A career counseling program for dentists: effects on burnout.
AB  - The effects on burnout of a career counseling program were measured among general
      dental practitioners. Out of a group of 171 dentists, identified with unfavorable
      scores on the Maslach Burnout Inventory - Dutch version (MBI-NL), nineteen chose
      to participate in the program. It consisted of individual counseling and group
      sessions, using cognitive and behavioral intervention techniques, over a 6-month
      period. One month after the last session, both program participants (N=17) and
      invited, but not participating, dentists (N=66) again filled in the MBI-NL.
      Comparison of participants' pre- and post-test scores showed significant
      statistical improvement on the MBI-NL scales emotional exhaustion (EE), and
      personal accomplishment (PA). Among the control group, a distinction was made
      between dentists who had self-initiated preventive measures (N=35) and those who
      had not (N=31). Self-prevention also appeared to have an effect on EE and PA.
      Among dentists who reported not to have undertaken preventive action, no change
      in burnout levels was found. With reservations, it can be concluded that the
      prevention program does have a positive effect on burnout scores among dentists,
      while different forms of self-initiated prevention activities also appeared to be
      effective.

PMID- 11311837
TI  - Knowledge and attitudes of high school teachers towards pupils suffering from
      chronic diseases.
AB  - Fifty-eight high school teachers participated in a study about their knowledge
      and attitudes concerning chronic disease in children and adolescents. The level
      of knowledge of the 58 teachers was 62%. The head teachers did not have a higher
      score for their knowledge (63.3%) as compared with vocational teachers (60.3%).
      The presence of chronic diseases among children of staff teachers correlated with
      higher knowledge. Head teachers did not show a more tolerant attitude toward
      pupils with chronic diseases than the vocational teachers (14.9% vs. 13.7%).
      Ninety percent of teachers are ready and willing to spend extra time teaching
      their chronically ill pupils. The head teachers meet more frequently with
      chronically ill pupils, as well as with their parents, than do vocational
      teachers. All teachers believe and expect that they should know details about the
      pupil's chronic condition; more head teachers than vocational think it is
      important and beneficial if other pupils in class would know about the chronic
      condition and handicaps of the specific pupils in their class. Three quarters of
      the teachers consider it important and mandatory to increase awareness of chronic
      disease and disability in the school setting.

PMID- 11311838
TI  - Usefulness of the retrospective Life-Chart method manual in outpatients with a
      mood disorder: a feasibility study.
AB  - The aim of this project was to evaluate whether the Life-Chart Manual (LCM) can
      help patients to complete their own Life-Chart (LC). All patients were recruited
      via the outpatient department for affective disorders of the Academic Hospital
      Maastricht. They were diagnosed as having a unipolar or bipolar disorder
      according to DSM-IV criteria. Following a short briefing interview, these
      patients were asked to complete their own LC for the last 6 years, using the
      manual. Seventy-four patients were selected, of whom 44 were willing to
      participate in the study. About half of these patients (n=20) completed the LC
      adequately (60-80% of the items completed) with only minimal professional help.
      Although patients found it difficult to complete the LC, most considered it
      worthwhile. The LCM is an adequate tool to help patients with a major affective
      disorder to complete their own LC with minimal professional assistance.

PMID- 11311839
TI  - Processing prescription drug information under different conditions of
      presentation.
AB  - OBJECTIVES: The purpose of this study was to investigate individuals' processing
      of prescription drug information under different conditions of presentation.
      DESIGN: Videotapes and written materials were used to develop 12 different
      conditions of presentation and data were collected via a mailed survey
      methodology. Controlling for respondent age, we studied respondents' perceptions
      of cognitive effort required to process the information, information overload,
      and evaluative response to the information. Also, we documented and studied the
      number of questions reported after exposure to the information. SUBJECTS: Study
      materials were mailed to 624 volunteers living in the United States, of which 477
      (76.4%) returned completed data forms. RESULTS AND CONCLUSIONS: The results
      suggest there is a balance between the need for information at a level sufficient
      for individuals to make decisions and the need for information that will not
      overload individuals as they cognitively process it.

PMID- 11311840
TI  - Patient-health care provider communication during chemotherapy treatment: the
      perspectives of women with breast cancer.
AB  - Recognition that communication plays a central role in the provision of quality
      patient care has led to learning more about interactions between patients and
      their health care providers. The present study examined interactions between
      women with breast cancer and their cancer care specialists from the patients'
      perspective during the time the women underwent chemotherapy treatment. In total
      40 women from two regional cancer centers were interviewed about their
      communication experiences. Prevalent themes identified from analysis of the
      interview transcripts could be classified into two main categories. One category
      focused on the nature of the information exchange and included the themes of
      interaction modes and the power of information. The second category reflected
      relationship issues and included the themes of roles and responsibilities and
      connectedness. From their narratives, several patient, professional, and
      contextual factors could be identified that influenced women's perceptions about
      the quality of their communication experience.

PMID- 11311841
TI  - Psychological response to prenatal genetic counseling and amniocentesis.
AB  - The purpose of the present study was to characterize the psychological status
      (attitudes toward selective abortion, perceived risk, comprehension, patient
      satisfaction, coping, and state anxiety) of pregnant women at increased risk for
      fetal genetic anomalies who were referred for prenatal genetic counseling and
      amniocentesis; to determine which of these factors would predict amniocentesis
      use; and to identify patient outcomes associated with counseling and testing.
      Participants were 129 women aged 18 years and older who had one or more fetal
      genetic risk factors. All were recruited from an urban women's health clinic. The
      results revealed elevated perceptions of risk and moderate state anxiety despite
      adequate comprehension of, and patient satisfaction with, the process and content
      of genetic counseling. Approximately 78% agreed to testing; those who consented
      were more likely to hold favorable attitudes toward abortion than those who
      refused. Post-counseling, women experienced decrease in their perceived risk of
      having a baby born with a birth defect although perceived risk estimates remained
      higher than actual risks. Anxiety was clinically elevated and highest at the pre
      counseling stage, though it dissipated to normal levels over time. Previous
      experience with prenatal diagnostic testing, increased perceived risk of a birth
      anomaly, and favorable attitudes toward abortion were independently associated
      with increased pre-counseling anxiety. Women who were more anxious pre-counseling
      remained more anxious post-counseling. Coping (high versus low monitoring) was
      unrelated to anxiety. These findings suggest that women who participate in
      prenatal counseling and testing may be subject to experience distress and
      unrealistic perceptions of their risk and may benefit from interventions designed
      to lessen these states.

PMID- 11311842
TI  - Lipids and psychosocial status in aboriginal persons with and at risk for Type 2
      diabetes: implications for tertiary prevention.
AB  - This study assessed psychosocial correlates of dyslipidemia, towards enabling
      improved tertiary prevention of macrovascular complications of diabetes mellitus
      (DM). We tested the hypothesis that psychosocial measures are related to high
      density lipoprotein cholesterol (HDL-C) and triglyceride concentrations in a
      rural aboriginal population in British Columbia, Canada. Persons sampled were on
      reserve registered Indians (n=198) with and at risk for Type 2 DM. Relationships
      between HDL-C and psychosocial variables were associated with glycemic status.
      For persons with diabetes and impaired glucose tolerance (n=44), quality of life
      and mastery were positively related (P<0.001), and depression inversely related
      (P<0.001), to HDL-C. An apparent lack of effect of behavior suggests the
      influence of emotional pathways involving autonomic-neuroendocrine axes. We
      recommend assessing mental health, and promoting mastery and diabetes quality of
      life through empowerment oriented diabetes management strategies, in negotiating
      culturally acceptable treatment of diabetic dyslipidemia for aboriginal people.

PMID- 11311843
TI  - The strategies used by general practitioners when providing information about
      medicines.
AB  - Changes both inside and outside the consultation increase the chances that
      patients may gain information from sources other than their general practitioner
      (GP). Data from nine interviews and one focus group with British GPs were used to
      explore GPs' rationale for the information they provide when prescribing oral
      steroids and their perceptions of patients' expectations. GPs' communication
      strategies were associated with the type of relationship they sought to
      perpetuate with patients. Some GPs reported that decisions about the provision of
      information were based on their own judgements of what patients needed to know
      (paternalistic approach), while others reported attempts to take account of
      patients' existing knowledge and beliefs (mutualistic approach). All the GPs were
      aware of the availability of information about medical matters, and most believed
      that patients' expectations had increased. The communication strategies of some
      GPs may not be appropriate given the availability of medical information outside
      the consultation.

PMID- 11311844
TI  - Playing games in promoting childhood dental health.
AB  - Oral health behaviour is a result of a life-long learning process, this process
      can best be achieved by an interdisciplinary collaboration among dentists and
      professionals in other areas, e.g. psychologists, teachers and kindergarten
      teachers. The basis of our research is a childhood dental health promotion
      programme which consists of a tool of games for children in the age of 3-5 years.
      After development by an interdisciplinary research group, the effectiveness of
      this teaching and behaviour modification technique should be proved. This study
      describes a controlled field study, in which two forms of game play activities
      were compared to a control groups. The results showed that the use of games and
      shows aimed at a child's developmental level can be more efficacious than the
      presentation of didactic information alone.

PMID- 11311845
TI  - Diabetes education program in Bulgaria.
AB  - The objective of the Diabetes Education Program for Bulgaria (DEPB) was to
      introduce a large-scale unified structured educational program for insulin
      treated diabetic patients. A total of 52 university and regional educational
      centers for people with diabetes and four centers for education of children with
      diabetes were organized. The educational course includes 10 sessions, 45min each,
      in 3-5 consecutive days for groups of 8-12 insulin-treated patients. To assess
      the effect of the DEPB on diabetes-related parameters data collection was
      organized in seven centers. It included 2055 patients who were allocated to
      education (intervention group) or not to be educated (control group). Diabetes
      related parameters were measured at baseline, and patients will be followed at 6
      months. Measuring the biochemical parameters, self-estimated knowledge, treatment
      satisfaction, burden and handling of diabetes before and after education would
      give the opportunity to evaluate its impact on the metabolic control and on
      psychological factors.

PMID- 11311846
TI  - Neuroregulation of growth hormone secretion in domestic animals.
AB  - Growth hormone (GH) is essential for postnatal somatic growth, maintenance of
      lean tissue at maturity in domestic animals and milk production in cows. This
      review focuses on neuroregulation of GH secretion in domestic animals. Two
      hormones principally regulate the secretion of GH: growth hormone-releasing
      hormone (GHRH) stimulates, while somatostatin (SS) inhibits the secretion of GH.
      A long-standing hypothesis proposes that alternate secretion of GHRH and SS
      regulate episodic secretion of GH. However, measurement of GHRH and SS in
      hypophysial-portal blood of unanesthetized sheep and swine shows that episodic
      secretion of GHRH and SS do not account for all episodes of GH secreted.
      Furthermore, the activity of GHRH and SS neurons decreases after steers have
      eaten a meal offered for a 2-h period each day (meal-feeding) and this
      corresponds with reduced secretion of GH. Together, these data suggest that other
      factors also regulate the secretion of GH. Several neurotransmitters have been
      implicated in this regard. Thyrotropin-releasing hormone, serotonin and gamma
      aminobutyric acid stimulate the secretion of GH at somatotropes. Growth hormone
      releasing peptide-6 overcomes feeding-induced refractoriness of somatotropes to
      GHRH and stimulates the secretion of GHRH. Norepinephrine reduces the activity of
      SS neurons and stimulates the secretion of GHRH via alpha(2)-adrenergic
      receptors. N-methyl-D,L-aspartate and leptin stimulate the secretion of GHRH,
      while neuropeptide Y stimulates the secretion of GHRH and SS. Activation of
      muscarinic receptors decreases the secretion of SS. Dopamine stimulates the
      secretion of SS via D1 receptors and inhibits the secretion of GH from
      somatotropes via D2 receptors. Thus, many neuroendocrine factors regulate the
      secretion of GH in livestock via altering secretion of GHRH and/or SS,
      communicating between GHRH and SS neurons, or acting independently at
      somatotropes to coordinate the secretion of GH.

PMID- 11311847
TI  - Secretion of dopamine and norepinephrine in hypophyseal portal blood and
      prolactin in peripheral blood of Holstein cattle.
AB  - The objective was to test the hypothesis that dopamine regulates prolactin (PRL)
      secretion by determining acute changes in catecholamine concentrations in
      hypophyseal portal blood of cattle, and their relation to peripheral blood
      concentration of PRL in hypophyseal stalk-transected (HST) and sham-operated
      controls (SOC). Holstein heifers (606 +/- 21 kg BW; mean +/- SE) were subjected
      to neurosurgery for 8 h to collect hypophyseal portal blood with a stainless
      steel cannula designed with a cuff placed under the pituitary stalk and
      peripheral blood via a jugular vein catheter. PRL plasma concentration was
      measured by radioimmunoassay, and dopamine and norepinephrine in portal plasma by
      radioenzymatic assay. During anesthesia before HST or SOC, PRL plasma
      concentration ranged from 20-40 ng/ml throughout 255 min. PRL abruptly increased
      and remained above 90 ng/ml after HST compared with a steady decrease to <20
      ng/ml in SOC heifers throughout 440 min. Within 5 min after severing the
      hypophyseal stalk, dopamine in portal blood (>8 ng/ml) was significantly
      increased (P < 0.05) compared with peripheral blood (<2 ng/ml). Norepinephrine
      concentration in portal blood was significantly greater (P < 0.05) than in
      peripheral blood during the first 60 min. The sustained high PRL level in
      peripheral plasma after severing the hypophyseal stalk stimulated hypothalamic
      dopamine secretion from hypophyseal portal vessels during the prolonged period of
      blood collection. Norepinephrine concentration in these cattle was greater in
      hypophyseal portal than in peripheral blood, implicating both an important
      hypothalamic source of the catecholamine as well as an adrenal gland contribution
      during anesthesia.

PMID- 11311848
TI  - Effect of hypomagnesemia and cold exposure on tissue responsiveness to insulin in
      sheep given a low magnesium and high potassium diet.
AB  - Hypomagnesemia in ruminants has been shown to be associated with cold stress and
      with altered insulin secretion and sensitivity. However, the relationship between
      hypomagnesemia and tissue responsiveness to insulin in ruminants exposed to cold
      environment is still unclear. The hyperinsulinemic euglycemic clamps, four
      insulin infusion rates (1, 2, 4 and 8 mU x kgBW(-1) x min(-1) for four sequential
      periods of 2-h each) were performed to determine combined effects of
      hypomagnesemia and cold exposure (0 degrees C) on tissue responsiveness to
      insulin in sheep. The low magnesium (0.05% Mg) and high potassium (4.20% K) diet
      and cold exposure decreased (P <.05) plasma Mg levels compared with those of the
      control diet (0.28% Mg/0.52% K) and the thermoneutral environment (20 degrees C).
      In the euglycemic clamps, cold exposure increased (P <.01) the pooled glucose
      infusion rate (GIR) across various insulin infusion rates in both diet
      treatments, though the increases in GIR were small for the low Mg/high K diet. In
      the cold environment, the GIR was lower (P <.01) for the low Mg/high K diet-fed
      sheep than for the control diet-fed sheep. The maximal insulin-induced increase
      in GIR was lower (P <.01) in the hypomagnesemic sheep than in the control sheep
      during cold exposure, and the insulin level resulting in half-maximal GIR tended
      to be higher in the hypomagnesemic sheep than in the control sheep. These results
      indicated that hypomagnesemia in ruminants depressed the enhanced tissue
      responsiveness to insulin in the cold environment, and decreased insulin-mediated
      glucose disposal.

PMID- 11311849
TI  - Persistent hypoglycemia is induced by tolbutamide administration in broiler
      chickens fed a low-carbohydrate diet.
AB  - With a view to gaining an insight into the regulatory mechanism of blood glucose
      concentrations specific to the chicken, an experimental induction of hypoglycemia
      was conducted by single or sequential administration of tolbutamide in broiler
      chickens fed a standard or low-carbohydrate diet. A single dosing of tolbutamide
      at levels of 25-200 mg/kg body weight decreased plasma glucose concentrations for
      2 to 8 h after the dosing in chickens fed either diet. No significant rise in
      plasma insulin concentration was observed for 2 to 24 h after the single dosing
      of tolbutamide in chickens on either diet, with the exception of a significant
      rise when chickens on the standard diet received 100 mg tolbutamide. However, a
      transient increase of plasma insulin concentration was observed only in the 20
      min immediately after the single dosing. Persistent hypoglycemia that was
      sustained for 5 days, with no significant changes in plasma insulin
      concentration, was induced by sequential dosing (3 times per day for 5 days,
      every 8 h) of tolbutamide (100 and 200 mg/kg body weight) in chickens fed the low
      carbohydrate diet. In these chickens, the consistently low concentration of
      plasma glucose, with small diurnal variations, was evidenced by the determination
      of plasma glucose every 3 h in day 4/5 of the tolbutamide dosing. In chickens fed
      the standard diet, on the other hand, the low plasma glucose concentrations for 5
      days were accompanied by significant diurnal fluctuations. Chickens with
      persistent hypoglycemia showed slight decreases in plasma non-esterified fatty
      acids (NEFA) concentration and only slight changes in blood D-3-hydroxybutyrate
      (3HB) concentration. The present study shows that the persistent hypoglycemia
      with normoinsulinemia, in the main, is induced by tolbutamide dosing in chickens
      fed a low-carbohydrate diet, and that the blood concentrations of NEFA and 3HB,
      alternatives of energy source in animals, are only slightly changed or not at all
      in hypoglycemic chickens.

PMID- 11311850
TI  - Growth hormone induces tyrosyl phosphorylation of the transcription factors
      Stat5a and Stat5b in CMT-U335 canine mammary tumor cells.
AB  - It has now been well documented that the normal and tumorous canine mammary
      glands can be extra-pituitary sites of substantial growth hormone (GH) synthesis.
      Until now, attempts to reproduce the GH synthesis in-vitro using canine mammary
      explants or mammary tumor cells have not been successful. Therefore, the response
      of CMT-U335 canine mammary tumor cells to administered porcine GH (pGH) was
      investigated as an in-vitro model to study the possible effects of GH synthesis
      on this site. CMT-U335 cells spontaneously express the growth hormone receptor
      (GHR) as well as the prolactin receptor (PRLR). Twenty five minutes after
      administration, GH induced, in a dose-dependent manner, phosphorylation of the
      transcription factors Stat5a and Stat5b. Clear phosphorylation was induced by 10(
      7) M and 10(-8) M pGH, with virtually no phosphorylation at 10(-9) M pGH. A
      similar dose-dependent phosphorylation of Stat5a by ovine prolactin was found in
      these cells. Although at high concentrations binding of pGH to the canine PRLR
      can occur (albeit with a low pKa), the similar dose-dependent effect of oPRL on
      Stat5a phosphorylation indicated that pGH signaled through the GHR. Remarkably,
      pGH induced a moderately decreased proliferation of CMT-U335 tumor cells, which
      may indicate that GH induces differentiation in these tumor cells. The GH-induced
      activation of Stat5a and Stat5b in these cells, as part of the JAK/Stat signal
      transduction pathway, is consistent with mammary GH playing a role in autocrine
      and/or paracrine stimulation of (tumorous) mammary cells.

PMID- 11311851
TI  - The porcine erythropoietin gene: cDNA sequence, genomic sequence and expression
      analyses in piglets.
AB  - The porcine erythropoietin (EPO) gene and its cDNA have been cloned and
      characterized. The cDNA encodes a protein of 194 amino acids. The gene structure
      and sequence show a high degree of homology to the corresponding human and murine
      gene. Steroid hormone receptor binding sites are present both in the promoter and
      in the 3' flanking region of the gene, which also contains an oxygen-sensing
      sequence. The promoter lacks classical promoter elements such as TATA and CAAT
      boxes. Expression analyses using a competitive RT-PCR assay showed that the
      kidneys contain about ten times more erythropoietin mRNA than the liver in five
      week-old piglets, thus indicating that the shift from mainly hepatic to mainly
      renal EPO production has taken place at this age. The testes showed a higher
      ratio of EPO mRNA to total RNA than the liver. Spleen showed very low levels of
      expression, while no expression of erythropoietin mRNA was detected in brain
      tissue, bone marrow, lung, lymph nodes, and ovaries.

PMID- 11311852
TI  - beta-Thymosins, small acidic peptides with multiple functions.
AB  - The beta-thymosins are a family of highly conserved polar 5 kDa peptides
      originally thought to be thymic hormones. About 10 years ago, thymosin beta(4) as
      well as other members of this ubiquitous peptide family were identified as the
      main intracellular G-actin sequestering peptides, being present in high
      concentrations in almost every cell. beta-Thymosins bind monomeric actin in a 1:1
      complex and act as actin buffers, preventing polymerization into actin filaments
      but supplying a pool of actin monomers when the cell needs filaments. Changes in
      the expression of beta-thymosins appear to be related to the differentiation of
      cells. Increased expression of beta-thymosins or even the synthesis of a beta
      thymosin normally not expressed might promote metastasis possibly by increasing
      mobility of the cells. Thymosin beta(4) is detected outside of cells in blood
      plasma or in wound fluid. Several biological effects are attributed to thymosin
      beta(4), oxidized thymosin beta(4), or to the fragment, acSDKP, possibly
      generated from thymosin beta(4). Among the effects are induction of metallo
      proteinases, chemotaxis, angiogenesis and inhibition of inflammation as well as
      the inhibition of bone marrow stem cell proliferation. However, nothing is known
      about the molecular mechanisms mediating the effects attributed to extracellular
      beta-thymosins.

PMID- 11311853
TI  - Kinetic properties of human placental glucose-6-phosphate dehydrogenase.
AB  - The kinetic properties of placental glucose-6-phosphate dehydrogenase were
      studied, since this enzyme is expected to be an important component of the
      placental protection system. In this capacity it is also very important for the
      health of the fetus. The placental enzyme obeyed "Rapid Equilibrium Ordered Bi
      Bi" sequential kinetics with K(m) values of 40+/-8 microM for glucose-6-phosphate
      and 20+/-10 microM for NADP. Glucose-6-phosphate, 2-deoxyglucose-6-phosphate and
      galactose-6-phosphate were used with catalytic efficiencies (k(cat)/K(m)) of 7.4
      x 10(6), 4.89 x 10(4) and 1.57 x 10(4) M(-1).s(-1), respectively. The K(m)app
      values for galactose-6-phosphate and for 2-deoxyglucose-6-phosphate were 10+/-2
      and 0.87+/-0.06 mM. With galactose-6-phosphate as substrate, the same K(m) value
      for NADP as glucose-6-phosphate was obtained and it was independent of galactose
      6-phosphate concentration. On the other hand, when 2-deoxyglucose-6-phosphate
      used as substrate, the K(m) for NADP decreased from 30+/-6 to 10+/-2 microM as
      the substrate concentration was increased from 0.3 to 1.5 mM. Deamino-NADP, but
      not NAD, was a coenzyme for placental glucose-6-phosphate dehydrogenase. The
      catalytic efficiencies of NADP and deamino-NADP (glucose-6-phosphate as
      substrate) were 1.48 x 10(7) and 4.80 x 10(6) M(-1)s(-1), respectively. With both
      coenzymes, a hyperbolic saturation and an inhibition above 300 microM coenzyme
      concentration, was observed. Human placental glucose-6-phosphate dehydrogenase
      was inhibited competitively by 2,3-diphosphoglycerate (K(i)=15+/-3 mM) and NADPH
      (K(i)=17.1+/-3.2 microM). The small dissociation constant for the G6PD:NADPH
      complex pointed to tight enzyme:NADPH binding and the important role of NADPH in
      the regulation of the pentose phosphate pathway.

PMID- 11311854
TI  - Bovine papillomavirus oncoprotein E5 affects the arachidonic acid metabolism in
      cells.
AB  - The bovine papillomavirus type 1 (BPV-1) oncoprotein encoded by the E5 ORF is a
      small highly hydrophobic protein, which is capable of inducing oncogenic
      transformation of cells. We studied the effect of the BPV-1 E5 protein expression
      on the arachidonic acid metabolism in monkey (COS1) and human (C33A) cells. At
      relatively low protein concentrations the phospholipase A(2) (PLA(2)) activity
      and the arachidonic acid (AA) metabolism are activated. E5 mutant proteins,
      lacking cysteines responsible for the dimerisation of the protein (C37S,
      C37SC39S), and truncated E5, lacking the C-terminal region, are non-transforming
      and unable to stimulate the PLA(2) activity and AA metabolism. The transformation
      defective mutant D33V, which does not activate the platelet-derived growth factor
      receptor (PDGFR), activates AA metabolism like wt E5. Our data suggest that the
      BPV-1 E5 protein could stimulate the AA metabolism independently of PDGF
      receptor.

PMID- 11311855
TI  - Oxygen modulates the release of urokinase and plasminogen activator inhibitor-1
      by retinal pigment epithelial cells.
AB  - The aims of this study were to examine the effect of oxygen, in the presence or
      absence of exogenous growth factors, on the release of plasminogen activators and
      plasminogen activator inhibitor-1 by cultured human retinal pigment epithelial
      cells. Antigen and activity levels of urokinase, tissue plasminogen activator and
      plasminogen activator inhibitor were measured in conditioned media after cells
      were exposed to three different oxygen environments: hypoxia, normoxia and
      hyperoxia. Overall proteolytic balance was determined by zymography. The effects
      of exogenous basic fibroblast growth factor and transforming growth factor-beta
      were also examined. it was found that retinal pigment epithelial cells released
      urokinase, tissue plasminogen activator and plasminogen activator inhibitor in
      measurable quantities. After 48 h, urokinase levels were highest at normoxia,
      reaching 7.2ng/10(6) cells (+/-2.0 SEM), whereas plasminogen activator inhibitor
      1 levels were highest at hyperoxia, reaching 67.5ng/10(6) cells (+/-3.7 SEM).
      Tissue plasminogen activator levels were minimal (<0.5ng/10(6) cells) and
      unaffected by both oxygen and growth factors. Overall proteolytic activity was
      also greatest at normoxia. Fibroblast growth factor stimulated urokinase
      production dose-dependently, but plasminogen activator inhibitor only minimally.
      Transforming growth factor-beta stimulated plasminogen activator inhibitor
      production dose-dependently but urokinase only at higher concentrations. These
      results suggest that both oxygen tension and growth factors may interact to
      modulate the proteolytic properties of the human retinal pigment epithelium.

PMID- 11311856
TI  - The ATP-binding site of brain phosphatidylinositol 4-kinase PI4K230 as revealed
      by 5'-p-fluorosulfonylbenzoyladenosine.
AB  - The ATP-binding site of purified bovine brain phosphatidylinositol 4-kinase 230
      (PI4K230) was studied by its reaction with 5'-p-fluorosulfonylbenzoyladenosine
      (FSBA), an ATP-like alkylating reagent. Four hundred to eight hundred micromolar
      FSBA inactivated PI4K230 specifically with apparently first-order kinetics and
      resulted in 50% loss of enzyme activity in 36--130 min. The specificity of the
      reaction with FSBA was demonstrated by the lack of inactivation with 5'-p
      fluorosulfonylbenzoyl chloride and by protection with ATP and ATP analogues
      against inactivation. Most ATP analogues competed with FSBA inactivation in order
      of their increasing hydrophobicity, parallel to their inhibitory potency in
      activity measurements. The specific binding of FSBA to PI4K230 was demonstrated
      also by Western-blot experiments. These results suggest that FSBA-reactive
      group(s) involved in the enzyme activity are located near to the ATP-binding site
      in a hydrophobic region of native PI4K230. Experiments with site-directed
      mutagenesis indicate that the conserved Lys-1792 plays essential role in the
      enzyme activity and serves as one target of affinity labelling by FSBA.
      Prevention of both Lys-1792-directed and Lys-1792-independent binding of FSBA by
      Cibacron Blue 3GA suggest that these sites are located spatially close to each
      other.

PMID- 11311857
TI  - Incorporation of 1-(14)C linoleic acid in rat liver nuclei and chromatin
      fractions.
AB  - The incorporation of 1-(14)C linoleic acid in several chromatin fractions of rat
      liver nuclei was investigated using two different procedures: (1) rat liver
      nuclei were incubated with ATP, CoASH, Mg(++) and 1-(14)C linoleic acid. After 40
      min at 37 degrees C the chromatin obtained by sonication of nuclei suspended in
      0.25 M sucrose was fractionated by differential sedimentation; (2) chromatin
      fractions obtained by differential sedimentation were incubated separately with
      ATP, CoASH, Mg(++) and 1-(14)C linoleic acid 40 min at 37 degrees C in order to
      characterize the fatty acid incorporation in isolated chromatin. A comparative
      study of the incorporation of 1-(14)C linoleic acid in microsomes and nuclei
      isolated from rat liver is also presented for the purpose of comparison. Linoleic
      acid was incorporated into nuclear lipids as well as in chromatin fractions. The
      fatty acid incorporation was stimulated considerably in the acylation system when
      compared to control, it appears to be highly dependent on the state of
      condensation of chromatin, being barely detectable in the lowest density
      fraction. The major proportion of 1-(14)C linoleic acid was found in
      phospholipids and in a lesser proportion it remained esterified to triglycerides
      and cholesteryl esters. The distribution of radioactivity in different classes of
      phospholipids present in microsomes and nuclei isolated from rat liver, showed a
      similar profile of distribution. The major proportion of radioactivity,
      approximately 50% was found in phosphatidylcholine and in a lesser proportion in
      sphingomyelin, phosphatidylserine and phosphatidylethanolamine. When chromatin
      fractions were incubated separately, it was observed that the major proportion of
      1-(14)C linoleic acid in phospholipids was found in heavy chromatin fractions
      whereas low density chromatin fraction only incorporated in a lesser proportion.

PMID- 11311858
TI  - Isolation of a novel heterodimeric agglutinin from rhizomes of Smilax glabra, the
      Chinese medicinal material tufuling.
AB  - A heterodimeric agglutinin with a molecular mass of 32 kDa, and comprised of a 15
      and a 17 kDa-subunit, was isolated from Smilax glabra rhizomes. The isolation
      protocol entailed ion exchange chromatography on CM-Sepharose, DEAE-cellulose and
      Resource Q and gel filtration on Superose 12. The two agglutinin subunits
      resembled each other and lectins from other Liliaceae plants in N-terminal
      sequence. The hemagglutinating activity of the agglutinin was unstable under
      acidic and alkaline conditions and when exposed to temperatures at or higher than
      50 degrees C. The activity was not altered by a number of monovalent, divalent
      and trivalent cations, nor by a variety of sugars and glycoproteins.

PMID- 11311859
TI  - Aggregation of creatine kinase during refolding and chaperonin-mediated folding
      of creatine kinase.
AB  - The course of refolding and reactivation of urea-denatured creatine kinase (ATP;
      creatine N-phosphotransferase, EC 2.7.3.2) has been studied in the absence and
      presence of molecular chaperonin GroEL. The enzyme was denatured in Tris--HCl
      buffer containing 6 M urea for 1 h. In the refolding studies, the denatured
      enzyme was diluted 60-fold into the same buffer containing GroEL or not for
      activity, turbidity, fluorescence measurements and polyacrylamide gel
      electrophoresis. The results show that the reactivation process is dependent of
      creatine kinase concentration in the concentration range 2.5--4 microM. The
      levels of activity recovery decrease with increasing enzyme concentration because
      of the formation of wrong aggregates. The molecular chaperonin GroEL can bind the
      refolding intermediate of creatine kinase and thus prevent the formation of wrong
      aggregates. This intermediate is an inactive dimeric form that is in a
      conformation resembling the 'molten globule' state.

PMID- 11311860
TI  - Isolation of a small chitinase-like antifungal protein from Panax notoginseng
      (sanchi ginseng) roots.
AB  - An antifungal protein, with a molecular weight of 15 kDa and an N-terminal
      sequence analogous to those of chitinases, was first isolated from the Chinese
      medicinal material Panax notoginseng, using cation exchange chromatography and
      affinity chromatography. The protein was adsorbed on CM-cellulose, Affi-gel Blue
      Gel and Mono S. It exerted antifungal activity against Coprinus comatus, Fusarium
      oxysporum and Mycosphaerella arachidicola but not against Rhizoctonia solani. The
      protein was devoid of ribonuclease activity against yeast tRNA.

PMID- 11311861
TI  - Hemoproteins affect H(2)O(2) removal from rat tissues.
AB  - The capacity of rat liver homogenates and mitochondria to remove H(2)O(2) was
      determined by comparing their ability to slow fluorescence generated by a
      H(2)O(2) 'detector' with that of desferrioxamine solutions. H(2)O(2) was produced
      by glucose oxidase-catalysed glucose oxidation. The capacity to remove H(2)O(2)
      was expressed as equivalent concentration of desferrioxamine. The method showed
      changes in the capacity of H(2)O(2) removal after treatment with ter
      butylhydroperoxide or glutathione. The H(2)O(2) removal capacity of homogenates
      and mitochondria from rat liver, heart, and skeletal muscle was compared with
      their overall antioxidant capacity. For homogenates, the order of both
      antioxidant and H(2)O(2) removal capacities was liver>heart>muscle. For
      mitochondria, the order of the antioxidant capacities mirrored that of the
      homogenates, while the order of the H(2)O(2) removal capacities was
      heart>muscle>liver. Because H(2)O(2) removal is not only due to H(2)O(2)
      metabolizing enzymes, but also to hemoproteins that convert H(2)O(2) into more
      reactive radicals via Fenton reaction, the higher concentration of cytochromes in
      mitochondria of cardiac and skeletal muscles can explain the above discrepancy. A
      higher H(2)O(2) removal capacity was found to be associated with a higher rate of
      H(2)O(2) release by mitochondria, indicating that the order of H(2)O(2) release
      rate mirrors that of H(2)O(2) production rate. We suggest that the different
      capacities of the mitochondria from the three tissues to produce reactive oxygen
      species are due to differences in the concentration of respiratory mitochondrial
      chain components in the reduced form.

PMID- 11311862
TI  - Interleukin-2 potentiates novelty- and GBR 12909-induced exploratory activity.
AB  - Interleukin (IL)-2 is a cytokine that influences exploratory behavior and central
      dopamine activity in rodents, and induces schizophrenic-like behavior and
      cognitive deficits in humans. We presently report that a single i.p. injection of
      murine IL-2 (0.05-0.80 microg/mouse) induced significant increases in novelty
      induced locomotion and exploration in BALB/c mice. These measures were not
      significantly altered in mice that were pre-exposed to the test cage prior to
      cytokine injection. The IL-2-induced behavioral changes were not further
      augmented by repeated intermittent injections (five daily i.p. injections; 0.4
      microg/mouse), however. Nonetheless, during the treatment period, activity scores
      of IL-2-treated mice significantly exceeded those of mice receiving saline;
      hence, repeated injections of IL-2 induced a persistent behavioral activation. IL
      2 treatment also increased sensitivity to the behavior-stimulating effects of GBR
      12909, a highly selective dopamine uptake inhibitor. This effect was a very long
      lasting one since the dopamine agonist was administered 6 weeks after cessation
      of IL-2 treatment. The latter finding indicates that IL-2 interacts with the
      mesolimbic dopamine system, changing its sensitivity to seemingly different
      substances. Based on these data, and those of Zalcman and colleagues (S. Zalcman,
      I. Savina, R.A. Wise, Interleukin-6 increases sensitivity to the locomotor
      stimulating effects of amphetamine in rats, Brain Res. 847 (1999) 276-283), it is
      suggested that cytokines can influence the development of behavioral
      abnormalities that are characteristic of aberrant mesolimbic dopamine activity
      via sensitization-like processes.

PMID- 11311863
TI  - Ribozyme-mediated inhibition of caspase-3 activity reduces apoptosis induced by 6
      hydroxydopamine in PC12 cells.
AB  - 6-Hydroxydopamine (6-OHDA) is a neurotoxin used in the induction of experimental
      Parkinson's disease in both animals and PC12 cells, which are derived from rat
      pheochromocytoma tumors and have many properties similar to dopamine neurons.
      Biochemical and molecular approaches have shown that low doses of 6-OHDA induce
      apoptosis in PC12 cells and, in the processing of apoptosis, caspases are crucial
      mediators, and caspase inhibition is sufficient to rescue PC12 cells from
      apoptosis induced by 6-OHDA. However, because this caspase inhibition targets
      multiple caspases, it is not known whether a single caspase is primarily
      responsible for effecting cell death in this model. To assess the particular
      member (caspase-3) of the ced-3 family relevant to cell death and to position
      their activation within the apoptotic pathway, we constructed a hammerhead
      ribozyme directed against rat caspase-3, which could downregulate the expression
      of caspase-3 in vitro and in vivo, and transfer to PC12 cells. The results show
      that the ribozymes against caspase-3 could protect PC12 cells from apoptosis
      induced by low doses of 6-OHDA. The PC12 cell transfected with the ribozymes
      shows a significant decrease in caspase-3 activity compared with control cells at
      various time points. Parallel to the reduced caspase-3 protease activity, similar
      decreased levels of apoptotic cells and DNA fragmentation were also assessed by
      staining with Hoechst 33258 and ELISA, respectively. Overexpression of p35, a
      general caspase inhibitor, also protected PC12 cells from apoptosis. These
      results confirm that caspases play an important role in 6-OHDA-induced PC12 cell
      apoptosis and indicate that caspase-3 itself is one of the crucial mediators of
      neurotoxin-induced PC12 cell apoptosis.

PMID- 11311864
TI  - Effect of novel stressors on gene expression of tyrosine hydroxylase and
      monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly
      immobilized rats.
AB  - Responses of central noradrenergic (NE) neurons to stressors like immobilization
      (IMO), cold exposure, insulin-induced hypoglycemia, and cellular glucoprivation
      caused by 2-deoxy-D-glucose (2-DG) were investigated in intact and long-term
      repeatedly immobilized (LTR, 2 h daily IMO for 41 days) rats. Expression of
      tyrosine hydroxylase (TH), norepinephrine transporter (NET) and vesicular
      monoamine transporter (VMAT2) genes were determined by using in situ
      hybridization histochemistry in brainstem A1, A2, A5 and locus coeruleus (LC)
      neurons. TH mRNA levels were increased by single IMO or 2-DG administration in
      all areas studied. Cold was effective only in LC and A2 neurons while insulin had
      no effect. LTR immobilization elevated TH mRNA levels in all investigated cell
      groups. These elevations were equally high to those elicited by a single IMO in
      each noradrenergic group, except the LC where LTR IMO was less effective than the
      single IMO. The levels of NET and VMAT2 mRNAs were elevated only in the A1 and A2
      cell groups of LTR IMO rats. A newly applied IMO in LTR rats did not alter TH,
      NET, and VMAT2 mRNA levels in any NE cell group investigated. Novel stressors
      like cold and 2-DG exaggerated the increased TH mRNA levels only in the LC of LTR
      IMO rats, unlike in the other NE cell groups. The present data indicate that
      repeated exposure of rats to homotypic stressor induces an adaptation of NE
      neurons, whereas single exposure of such animals to heterotypic novel stressor
      produces an exaggerated response of the system at the level of TH (in LC) and NET
      (in A1, A2) gene expression.

PMID- 11311865
TI  - Representational overlap of adjacent fingers in multiple areas of human primary
      somatosensory cortex depends on electrical stimulus intensity: an fMRI study.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine the influence of
      non-painful electrical stimulus intensity on the BOLD response in human primary
      somatosensory cortex (SI). In ten healthy subjects, index and middle finger of
      the right hand were stimulated separately at two different stimulus intensities.
      The activated volume of single finger representations as well as the volume of
      representational overlap of the two activations increased following an increase
      in stimulus intensity. This effect was seen in two different subdivisions of SI,
      one in the depth of the central sulcus, presumably corresponding to Brodmann area
      (BA) 3b, and one on the crown of the postcentral gyrus, presumably corresponding
      to BA 1/2. Relative overlap (ratio of overlap volume to volume of individual
      finger representation) was larger in BA 1/2 than in BA 3b. Additionally, in both
      areas relative overlap increased significantly from low to high stimulus
      intensity. Relative overlap did not change when different correlation thresholds
      were employed arguing against an unspecific 'spillover effect'. Analysis of
      signal intensity time courses indicated that the response difference to high
      versus low stimulus strength was not present during the initial seconds of
      stimulation, during which both led to a similar signal intensity increase. Only
      during the following maintenance level of the response did the response to high
      stimulus intensity reach a significantly higher plateau level than the one due to
      low intensity stimulation, an effect which was present in both areas, BA 3b and
      BA 1/2, respectively.

PMID- 11311866
TI  - Comparison of spinal myotatic reflexes in human adults investigated with cross
      correlation and signal averaging methods.
AB  - A cross-correlation method for recording spinal myotatic reflexes has been
      developed to meet the need for brief test periods in babies and children and
      subjects with central neurological pathology. In normal adult subjects the method
      has been validated by comparing excitatory and inhibitory reflexes obtained with
      cross-correlation with those obtained with conventional signal averaging. In the
      cross-correlation method a pseudo-random binary sequence of 64 brief tendon taps
      was delivered in <1.5 s, and in the averaging method 20-150 taps at one per
      second. The reflexes were expressed as unit impulse responses to enable direct,
      quantitative comparisons to be made. With cross-correlation the responses were
      slightly expanded in time, had lower peak amplitudes, and onset latencies
      advanced by 10 ms, the clock period of the pseudo-random binary sequence. The
      amplitude of biceps phasic stretch reflex increased with muscle contraction in a
      similar manner with both methods. In tests for stationarity the amplitude of
      biceps phasic stretch reflex varied <10% in the first six repeats of the pseudo
      random binary sequence. The tap force required at threshold for cross-correlation
      was approximately half that for averaging, but with both methods the magnitude of
      biceps phasic stretch reflex varied linearly with tap force over the range of one
      to two times threshold. The validity of responses obtained with cross-correlation
      was assessed by a statistical procedure. In conclusion, the cross-correlation
      method is robust and gives similar results to those obtained with averaging.

PMID- 11311867
TI  - Reciprocal and Renshaw (recurrent) inhibition are functional in man at birth.
AB  - The aims were (1) to determine when in human postnatal development Group Ia
      reciprocal and Renshaw inhibition can be demonstrated; (2) to explore the
      relationship between the expression reciprocal inhibition and the disappearance
      of Group Ia excitatory reflexes between agonist and antagonist muscles. Studies
      were performed on 99 subjects, aged 1 day to 31 years, of whom 53 were neonates.
      A longitudinal study was also performed on 29 subjects recruited at birth and
      studied 3 monthly until 12 months of age. Reciprocal inhibitory and excitatory
      reflexes were recorded in the surface EMG of contracting biceps brachii (Bi),
      evoked by taps applied to the tendon of triceps brachii (Tri). Reciprocal
      excitatory reflexes were recorded in all but one neonate. Reciprocal inhibition
      was observed in 25% of neonates; evidence is provided that it was likely to have
      been masked by low threshold reciprocal excitation in the remaining neonates.
      Reciprocal inhibition was demonstrated in all subjects after 9 months of age. In
      four neonates there was depression of inhibition of Bi during co-contraction of
      Bi and Tri implying that Group Ia interneurones may be under segmental and
      suprasegmental control at birth. Renshaw cells, identified in human postmortem
      cervical spinal cord by their morphology, location and calbindin D28K
      immunoreactivity, were present at 11 weeks post-conceptional age (PCA) and by 35
      weeks PCA had mature morphological characteristics. In four neonates reciprocal
      inhibitory responses in Bi disappeared when the tap to Tri evoked its own
      homonymous phasic stretch reflex, providing neurophysiological evidence for
      Renshaw inhibition of Group Ia inhibitory interneurones.

PMID- 11311868
TI  - Short latency heteronymous excitatory and inhibitory reflexes between antagonist
      and heteronymous muscles of the human shoulder and upper limb.
AB  - The aims were (i) to investigate heteronymous excitatory and inhibitory Group Ia
      reflexes linking agonist/antagonist muscle pairs acting at the shoulder and
      elbow; clavicular pectoralis major (Pmajor) and posterior deltoid (Pdeltoid);
      biceps brachii (Bi) and Tri brachii (Tri), and linking muscles acting at the
      elbow (Bi and Tri) with muscles acting at the shoulder (Pmajor and Pdeltoid).
      (ii) To test the hypothesis that the excitability of the reflexes would vary
      between different tasks in a functionally relevant manner. The study was
      performed on 45 adults. Reflexes were recorded in the surface EMG when the target
      muscle was contracting at 10% maximum voluntary contraction. Reflexes were
      recorded in Bi and Tri with the elbow joint in one of three positions: 105
      degrees, 80 degrees, or 55 degrees from full extension. Group Ia reflexes were
      evoked using a small, brief tap to the tendon of the muscle being stimulated.
      Reflexes were recorded by cross-correlation of the surface EMG and pseudo-random
      series of taps. All subjects demonstrated short latency inhibition and excitation
      between agonist/antagonist muscle pairs; inhibition was significantly more
      frequent than excitation. Excitation and inhibition occurred with equal frequency
      between muscle pairs acting between elbow and shoulder. Minimum central delays
      for excitatory reflexes were 1 ms, consistent with monosynaptic projections and
      for inhibitory responses were 2 ms consistent with disynaptic linkage. Later
      excitatory and inhibitory reflexes with central delays of up to 15 ms also
      occurred. The probability of evoking excitation or inhibition in Tri or Bi
      changed with the different elbow positions.

PMID- 11311869
TI  - Nicotine sensitization increases dendritic length and spine density in the
      nucleus accumbens and cingulate cortex.
AB  - This study investigated the effects of repeated administrations of nicotine (0.7
      mg/kg) on dendritic morphology in the nucleus accumbens (NAcc), prefrontal cortex
      (Cg 3), and parietal cortex (Par 1). Animals were habituated for 3 days to a
      locomotor box, and after habituation, every second day for 5 weeks rats were
      placed into the locomotor chamber immediately after a subcutaneous injection of
      nicotine or saline. Rats demonstrated tolerance to an initial hypoactive response
      after each nicotine injection, and this was followed by an increase in activity
      after each injection (behavioral sensitization). This increase in activity was
      still present on a nicotine challenge after a 2-week abstinence period. One week
      after the nicotine challenge day, all rats were perfused and brains were removed.
      These brains we stained using Golgi-Cox procedures, and dendrites from the
      nucleus accumbens (N Acc), medial frontal cortex (Cg 3) and parietal cortex (Par
      1) were analyzed using the camera lucida procedure. Results showed that rats
      receiving nicotine demonstrated an increase in dendritic length and spine density
      relative to controls in the NAcc and Cg3 brain areas, but not Par 1. The increase
      observed in the NAcc was significantly greater than what has been found with
      amphetamine or cocaine, and possible underlying mechanisms were discussed.

PMID- 11311870
TI  - Fos rhythms in the hypothalamus of Rattus and Arvicanthis that exhibit nocturnal
      and diurnal patterns of rhythmicity.
AB  - This study compared patterns of Fos expression within the suprachiasmatic nucleus
      (SCN), the region immediately dorsal to the SCN (the lower subparaventricular
      zone, LSPV), and the supraoptic nucleus (SON) of grass rats (Arvicanthis
      niloticus) and lab rats (Rattus norvegicus). Among grass rats we also compared
      individuals exhibiting nocturnal and diurnal patterns of wheel running. In the
      SCN of both groups of grass rats, as well as laboratory rats, Fos was elevated
      during the light compared to the dark portions of the day, and was expressed in 7
      12% of cells containing vasoactive intestinal polypeptide (VIP). Fos was higher
      in the LSPV during the night compared to the day in both forms of grass rats but
      not in laboratory rats. In the SON, Fos rose from day to night in the diurnal
      grass rats and in laboratory rats, but not in nocturnal grass rats. These
      patterns are consistent with the hypothesis that VIP cells in the SCN function
      similarly in nocturnal and diurnal rodents, but that the SON and the region
      dorsal to the SCN are associated with intra and interspecific differences in
      rhythmicity, respectively.

PMID- 11311871
TI  - Biogenic amines in the human neocortex in patients with neocortical and mesial
      temporal lobe epilepsy: identification with in situ microvoltammetry.
AB  - Biogenic amines in well defined subtypes of human temporal lobe epilepsy (TLE)
      have not been well characterized. Specimens from five patients with neocortical
      TLE (NTLE) and nine with mesial TLE (MTLE) were immediately placed in Ringer's
      lactate; stearate indicator microelectrodes were placed in temporal gray matter,
      Ag/AgCl reference microelectrodes and auxiliary microelectrodes were placed 3-7
      mm contralaterally to the indicator microelectrode. Dopamine (DA), ascorbic acid
      (AA), norepinephrine (NE) and serotonin (5-HT) were identified by their
      characteristic oxidative potentials in vitro. Four of five patients with NTLE had
      NE depletion in temporal neocortex while eight of nine patients with MTLE had
      high concentrations of NE (chi-square P<0.01). Significant concentrations of DA
      were present in the temporal lobes of three of five NTLE patients but in only one
      of the nine MTLE patients (chi-square P<0.05). 5-HT was present in the neocortex
      of both NTLE and MTLE patients in similar concentrations. AA was found in the
      neocortex of one NTLE patient. These data support an association between NE
      depletion and NTLE. The relative NE deficiency along with the consistent presence
      of DA in NTLE patients suggest an impairment in the catecholamine pathway. The
      presence of AA, a co-factor in NE synthesis, in the neocortex of one NTLE patient
      may also be related since AA is a cofactor in NE synthesis.

PMID- 11311872
TI  - Expression and localization of cytochrome P450 17 alpha-hydroxylase/c17,20-lyase
      in the avian brain.
AB  - Steroids synthesized de novo from cholesterol in the brain are generally called
      neurosteroids. We have recently demonstrated, using biochemical and molecular
      biological methods, that certain structures in the quail brain possess cytochrome
      P450 side-chain cleavage enzyme (P450scc) and 3beta-hydroxysteroid
      dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD) and produce pregnenolone,
      pregnenolone sulfate and progesterone. To clarify the biosynthetic pathway of
      neurosteroids in the avian brain, therefore, we examined the expression of
      messenger RNA (mRNA) encoding for the enzyme cytochrome P450 17alpha
      hydroxylase/c17,20-lyase (P450(17alpha,lyase)), which converts pregnenolone to
      dehydroepiandrosterone via 17alpha-hydroxypregnenolone or progesterone to
      androstenedione via 17alpha-hydroxyprogesterone. RT-PCR analysis followed by
      Southern hybridization indicated the expression of P450(17alpha,lyase) mRNA in
      the brain of sexually mature birds without a clear-cut sex difference. Employing
      biochemical techniques combined with HPLC analysis, the conversion of
      progesterone to 17alpha-hydroxyprogesterone was also found in brain slices of the
      mature male. P450(17alpha,lyase) mRNA was detected in various brain regions, but
      there was a clear regional difference in the expression. The expressions of
      P450(17alpha,lyase) mRNA in the diencephalon and mesencephalon were significantly
      higher than those in the cerebrum and cerebellum, unlike 3beta-HSD mRNA, which
      showed no regional difference in the expression. In situ hybridization revealed
      the cellular localization of P450(17alpha,lyase) mRNA. The cells expressing
      P450(17alpha,lyase) mRNA were detected several diencephalic and mesencephalic
      regions, such as the preoptic area, the anterior hypothalamus, the dorsolateral
      thalamus, the optic tectum and the ventral midbrain. The expression was also
      localized in the septum, the hyperstriatum accessorium, and the ventral portions
      of the archistriatum in the telencephalon. Cerebellar Purkinje cells also
      expressed P450(17alpha,lyase) mRNA. These results suggest that the avian brain
      possesses P450(17alpha,lyase) as well as P450scc and 3beta-HSD in both sexes. The
      expression of P450(17alpha,lyase) in the avian brain may be region-dependent.

PMID- 11311873
TI  - Perineuronal nets in the rat medial nucleus of the trapezoid body surround
      neurons immunoreactive for various amino acids, calcium-binding proteins and the
      potassium channel subunit Kv3.1b.
AB  - Perineuronal nets (PNs) are known as chondroitin sulfate-rich, lattice-like
      coatings of the extracellular matrix ensheathing mainly GABAergic, parvalbumin
      containing neurons especially in the cerebral cortex. PNs have also been detected
      around GABA-immunonegative cells which were shown to be not aminergic,
      cholinergic, nitrinergic or peptidergic in various brain regions of some
      mammalian species. To find out whether glycine and aspartate may occur in net
      bearing neurons the present study was focused on the rat medial nucleus of the
      trapezoid body (MNTB) which contains a large portion of cells immunoreactive for
      these amino acids, but appears to be devoid of GABA-immunoreactive cell bodies.
      PNs were detected around many glycine- and aspartate-immunopositive neurons in
      the MNTB by carbocyanine double labeling and confocal laser scanning microscopy.
      An additional finding was that the lectin-cytochemically stained extracellular
      matrix surrounds the calretinin-immunoreactive calyces of Held known as giant
      glutamatergic endbulbs which cover glycinergic principal cells in the MNTB. As
      elucidated by triple fluorescence labeling, the vast majority of somata co
      expressed the calcium-binding proteins parvalbumin and calbindin, but not
      calretinin. The observed co-localization of PNs and immunoreactivity for the
      voltage-dependent potassium channel Kv3.1b - as an established marker of fast
      firing parvalbumin-containing neurons - supports the assumed function of PNs as a
      cation exchanger ensuring rapid ion transport as required by highly active nerve
      cells.

PMID- 11311874
TI  - Interactions among glucose, lactate and adenosine regulate energy substrate
      utilization in hippocampal cultures.
AB  - Glucose is the major energy source during normal adult brain activity. However,
      it appears that glial-derived lactate is preferred as an energy substrate by
      neurons following hypoxia-ischemia. We examined factors influencing this switch
      in energetic bias from glucose to lactate in cultured hippocampal neurons,
      focusing on the effects of the physiological changes in lactate, glucose and
      adenosine concentrations seen during hypoxia-ischemia. We show that with typical
      basal concentrations of lactate and glucose, lactate had no effect on glucose
      uptake. However, at the concentrations of these metabolites found after hypoxia
      ischemia, lactate inhibited glucose uptake. Reciprocally, glucose had no effect
      on lactate utilization regardless of glucose and lactate concentrations.
      Furthermore, we find that under hypoglycemic conditions adenosine had a small,
      but significant, inhibitory effect on glucose uptake. Additionally, adenosine
      increased lactate utilization. Thus, the relative concentrations of glucose,
      lactate and adenosine, which are indicative of the energy status of the
      hippocampus, influence which energy substrates are used. These results support
      the idea that after hypoxia-ischemia, neurons are biased in the direction of
      lactate rather than glucose utilization and this is accomplished through a number
      of regulatory steps.

PMID- 11311875
TI  - Time-course of changes in firing rates and firing patterns of subthalamic nucleus
      neuronal activity after 6-OHDA-induced dopamine depletion in rats.
AB  - The subthalamic nucleus (STN) plays a key role in motor control. Disorganization
      of its neuronal activity is implicated in the manifestation of parkinsonian motor
      symptoms. The aim of the present work was to study the time-course of changes in
      the firing activity of STN neurons in a rat model of parkinsonism.
      Electrophysiological recordings were done in normal rats and four groups of rats
      at different time points after 6-hydroxydopamine (6-OHDA) microinjection into the
      pars compacta of substantia nigra (SNc). Results showed a significant decrease in
      firing rate during the first and second weeks post lesion (5.53+/-0.56 and 7.66+/
      0.73 spikes/s, respectively) compared to normal rats (11.13+/-0.59 spikes/s).
      From the 3rd week after 6-OHDA injection the firing rates returned toward
      baseline, with an average of 9.71+/-0.51 spikes/s during the 3rd week and 11.13+/
      0.71 spikes/s during the 4th week. With regard to firing pattern, the majority of
      STN cells (90%) discharged regularly or slightly irregularly in normal animals.
      Only 4% exhibited burst activity and 6% had mixed firing patterns. After SNc
      lesion, the percentage of cells exhibiting burst and mixed patterns increased
      progressively from 35% during the first week to 56% at week 4 post-lesion. In
      sum, these experiments revealed that the firing rate of STN neurons was altered
      only transiently following nigral lesions, whereas a progressive and stable
      change in the firing pattern was observed up to 4 weeks post lesion, suggesting
      that the persistence of bursts firing more closely relates to the motor
      pathologies of this rat model of parkinsonism.

PMID- 11311876
TI  - Cyclosporin A, but not FK506, prevents the downregulation of phosphorylated Akt
      after transient focal ischemia in the rat.
AB  - The two immunosuppressants, cyclosporin A (CsA) and FK506, when given 1 and 3 h
      after the start of reperfusion following 2 h of middle cerebral artery (MCA)
      occlusion, reduce infarct volume to 30% of control. This suggests a common
      effect, e.g. one due to suppression of the activation of calcineurin. However,
      when given by the intracarotid (i.c.) route after only 5 min of recirculation
      CsA, but not FK506, reduced infarct volume even further, to 10% of control. This
      was attributed to the fact that CsA, but not FK506, block the in vitro assembly
      of a mitochondrial permeability transition (MPT) pore. The present experiments
      were undertaken to further characterize the anti-ischemic effect of CsA, when
      given i.c. 5 min after recirculation and to explore why CsA, when given at that
      time, is more efficacious than FK506. It was established that the i.c.
      administration of CsA in a dose of 10 mg/kg increased the tissue concentration of
      CsA 2- to 3-fold, when compared to the i.v. administration. CsA proved to be
      effective in reducing infarct volume even when the tissue damage was assessed by
      histopathology after 7 days of recovery. MCA occlusion of 2 h duration caused a
      sustained decrease in the phosphorylation Akt at threonine 308. Since this down
      regulation of Akt was prevented by CsA, the results suggested a link between
      dephosphorylaltion of Bad, and cell death. Interestingly FK506 did not prevent
      down regulation of Akt, it thus seems unlikely that the anti-ischemic effect of
      CsA is related to its association with cytosolic cyclophilin.

PMID- 11311877
TI  - 5-HT1A and 5-HT2 receptors differentially regulate the excitability of 5-HT
      containing neurones of the guinea pig dorsal raphe nucleus in vitro.
AB  - We have used intracellular recording techniques to examine the effects of 5
      hydroxytryptamine (5-HT, serotonin) on 5-HT-containing neurones of the guinea pig
      dorsal raphe nucleus in vitro. Bath-applied 5-HT (30-300 microM) had two opposing
      effects on the membrane excitability of these cells, reflecting the activation of
      distinct 5-HT receptor subtypes. As demonstrated previously in the rat, 5-HT
      evoked a hyperpolarization and inhibition of 5-HT neurones, which appeared to
      involve the activation of an inwardly rectifying K(+) conductance. This
      hyperpolarizing response was blocked by the 5-HT(1A) receptor-selective
      antagonist WAY-100635 (30-100 nM). In the presence of WAY-100635, 5-HT induced a
      previously unreported depolarizing, excitatory response of these cells, which was
      often associated with an increase in the apparent input resistance of the
      neurone, likely due to the suppression of a K(+) conductance. Like the
      hyperpolarizing response to 5-HT, this depolarization could be recorded in the
      presence of the Na(+) channel blocker tetrodotoxin. In addition, the response was
      not significantly attenuated by the alpha(1)-adrenoceptor antagonist prazosin
      (500 nM), indicating that it is not due to the release of noradrenaline, or to
      the direct activation of alpha(1)-adrenoceptors by 5-HT. The 5-HT(3) receptor
      antagonist granisetron (1 microM) and the 5-HT(4) receptor antagonist SB 204070
      (100 nM) failed to reduce the depolarizing response to 5-HT; however, ketanserin
      (100 nM), mesulergine (100 nM) and lysergic acid diethylamide (1 microM)
      significantly reduced or abolished the depolarization, indicating that this
      effect of 5-HT is mediated by 5-HT(2) receptors.

PMID- 11311878
TI  - Microglial activation, emergence of ED1-expressing cells and clusterin
      upregulation in the aging rat CNS, with special reference to the spinal cord.
AB  - With advancing age, the incidence of neuronal atrophy and dystrophy increases
      and, in parallel, behavioural sensorimotor impairment becomes overt. Activated
      microglia has been implicated in cytotoxic and inflammatory processes in
      neurodegenerative diseases as well as during aging. Here we have used
      immunohistochemistry and in situ hybridization to examine the expression of OX42,
      ED1, ED2, GFAP and clusterin in CNS of young adult and behaviourally tested aged
      rats (30-month-old), to study the occurrence of activated microglia/ED1 positive
      macrophages in senescence and to what extent this correlates with astrogliosis
      and signs of sensorimotor impairment among the individuals. The results show a
      massive region-specific increase in activated microglia and ED1 expressing cell
      profiles in aged rats. The infiltration was most prominent in the spinal cord
      dorsal columns, including their sensory relay nuclei, and the outer portions of
      the lateral and ventral columns. At such sites the occurrence of macrophages
      coincided with increased levels of GFAP and positive correlations were evident
      between the labeling for, on the one hand, OX42 and, on the other, GFAP and ED1.
      Also, the ventral and dorsal roots were heavily infiltrated by ED1 positive
      cells. The signs of gliosis were most pronounced among aged rats with advanced
      sensorimotor impairment. In contrast, the grey matter of aged rats showed very
      few activated microglia/ED1 labeled cells despite signs of focal astrogliosis.
      ED2 expression was confined to perivascular cells and leptominges with a similar
      labeling pattern in young and aged rats. In aged rats increased expression of
      clusterin was observed in GFAP-immunoreactive profiles of the white matter only.
      It is suggested that this increase may reflect a response to
      degenerative/inflammatory processes.

PMID- 11311879
TI  - Circadian rhythm of drinking and running-wheel activity in rats with 6
      hydroxydopamine lesions of the ventral tegmental area.
AB  - Circadian rhythms in drinking and running-wheel (locomotor) activity of rats with
      6-hydroxydopamine (6-OHDA, 4 microg/2 microl per rat)-induced lesions in the
      ventral tegmental area (VTA) were examined under a light-dark (LD) cycle and
      constant dim light (5 lux). Under the LD cycle, the length of the locomotor
      activity period was decreased during the dark, and increased during the light
      period in the lesioned rats. Under the constant dim light conditions, the free
      running circadian period (tau) of drinking and activity rhythm was longer in
      lesioned rats than in sham-operated controls. The elongation of the circadian
      period was accompanied by decrements in activity. These observations suggest that
      the mesolimbic dopaminergic system modulates rhythms in circadian drinking and
      locomotor activity.

PMID- 11311880
TI  - Vasopressin reverses aluminum-induced impairment of synaptic plasticity in the
      rat dentate gyrus in vivo.
AB  - Aluminum (Al), an important neurotoxin, contributes to a variety of cognitive
      dysfunction and mental diseases. Previous studies have demonstrated that Al
      impairs hippocampal long-term potentiation (LTP) in vitro and in vivo. In the
      present study, both LTP and LTD (long-term depression) were recorded in the same
      animal to investigate the Al-induced impairment of synaptic plasticity. Another
      aim of the present research was to verify whether the impairment of synaptic
      plasticity induced by Al could be reversed by vasopressin (VP) treatment.
      Neonatal Wistar rats were exposed to Al from parturition through adulthood (pre-
      and post-weaning) by the drinking of 0.3% aluminum chloride (AlCl(3)) solution.
      The input-output (I/O) function, paired-pulse reaction (PPR), excitatory
      postsynaptic potential (EPSP) and population spike (PS) amplitude were measured
      in the dentate gyrus (DG) of adult rats (60-90 days) in response to stimulation
      applied to the lateral perforant path. The results showed: (1) Al reduced the
      amplitudes of both EPSP LTP (control: 132+/-7%, n=7; Al-exposed: 115+/-10%, n=8,
      P<0.05) and PS LTP (control: 242+/-18%, n=7; Al-exposed: 136+/-7%, n=8, P<0.01)
      significantly. The amplitudes of EPSP LTD (control: 82+/-6%, n=7; Al-exposed:
      92+/-7%, n=8, P<0.05) and PS LTD (control: 81+/-4%, n=7; Al-exposed: 98+/-5%,
      n=8, P<0.05) were also decreased by Al treatment. The Al-induced impairments of
      PS LTP and PS LTD were more serious than that of EPSP LTP and EPSP LTD. (2) In
      control rats, VP had an increase in the PS LTP amplitude (control: 242+/-18%,
      n=7; control+VP: 358+/-23%, n=6, P<0.01), while it had no significant effects on
      PS LTD (control: 81+/-4%, n=7; control+VP: 76+/-7%, n=6, P>0.05). (3) In Al
      exposed rats, VP had a significant increase in the amplitudes of both PS LTP (Al
      exposed: 136+/-7%, n=8, Al-exposed+VP: 255+/-16%, n=6, P<0.01) and PS LTD (Al
      exposed: 98+/-5%, n=8; Al-exposed+VP: 81+/-6%, n=6, P<0.05). After the
      application of VP, the range of synaptic plasticity (PS LTP+PS LTD) in Al-exposed
      rats increased from 38% to 174%, which surpassed that in control rats (161%). It
      was suggested that VP could reverse Al-induced impairment of synaptic plasticity
      and might be an effective medicine to cure Al-induced neurological disorders.

PMID- 11311881
TI  - Contribution of excitatory amino acids to hypoglycemic counter-regulation.
AB  - We determined the contribution of central N-methyl-D-aspartate (NMDA) receptor
      activation to the neuro-endocrine counter-regulatory response to insulin-induced
      hypoglycemia. Glucose kinetics, gluconeogenic substrate balance and counter
      regulatory hormonal responses were determined in two groups of conscious dogs
      fitted with chronic vascular catheters and intracerebroventricular (i.c.v.)
      cannula. Peripheral insulin infusion (5 mU/kg per min for 3 h) decreased plasma
      glucose levels 40% and increased the rate of glucose appearance (R(a)) 2-fold.
      This was associated with significant increases in net hepatic uptake of glycerol
      and lactate, without any change in the net hepatic uptake of alanine. i.c.v.
      pretreatment with MK-801, an NMDA receptor antagonist, blunted (50%) the rise in
      glucose R(a) as well as the increase in the net hepatic uptake of glycerol and
      lactate. Hypoglycemia increased plasma cortisol (3-fold to 14.3+/-1 mg/dl) and
      epinephrine levels (14-fold to 3811+/-172 pg/ml), and this stress response was
      attenuated (30% and 60%, respectively) by MK-801 pretreatment. In controls, MK
      801 did not alter the increase in norepinephrine or glucagon elicited by
      hypoglycemia. These results indicate that during hypoglycemia, central excitatory
      amino acids contribute to the modulation of the glucoregulatory response through
      activation of NMDA receptors, resulting in stimulation of the sympathoadrenal and
      hypothalamic-pituitary adrenal axis. This mechanism appears to play an important
      role in the sustained elevation in hepatic glucose production during
      hypoglycemia.

PMID- 11311882
TI  - Enhanced leptin transport across the blood-brain barrier by alpha 1-adrenergic
      agents.
AB  - Leptin is a 16 kDa protein secreted by fat cells which regulates body weight and
      thermogenesis at sites within the brain. Blood-borne leptin reaches those brain
      sites because of a saturable transport system located at the blood-brain barrier
      (BBB). Impaired transport occurs in obese rodents and likely underlies the
      resistance to the actions of peripheral leptin seen in obesity. Here, we show
      that leptin transport into the brain is enhanced 2-3-fold by epinephrine and
      other agents which are more specific for the alpha1 adrenergic receptor.
      Epinephrine had no effect on the transport across the BBB of insulin or tumor
      necrosis factor, on BBB integrity, or on the size of the vascular space of the
      brain. Dopamine, acetylcholine, histamine, serotonin, thyroid hormones, and
      phentolamine were without effect. Of several amino acids tested, only the
      catecholamine precursor tyrosine had an effect on leptin transport. Epinephrine
      was effective after intravenous or intraperitoneal injection, but neither
      epinephrine nor any of the other monoamines given by intracerebroventricular
      injection had an effect on leptin transport. These results show that epinephrine
      likely acts at a site on the luminal surface of the BBB. In conclusion,
      epinephrine works at an alpha1-like adrenergic, luminal side to enhance the
      transport of leptin across the BBB.

PMID- 11311883
TI  - Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning
      measured with fear-potentiated startle.
AB  - Considerable advances have been made in understanding the neurocircuitry
      underlying the acquisition and expression of Pavlovian conditioned fear
      responses. Within the complex cellular and molecular processes mediating
      fearfulness, amygdaloid dopamine (DA), originating from cells in the ventral
      tegmental area (VTA) of the midbrain, is thought to contribute to fear-motivated
      responding. Considering that blockade of DA D(2) receptors is a common mechanism
      of action for antipsychotic agents, we hypothesized that inhibition of D(2)
      receptors in the amygdala may be involved in the antiparanoid effects of these
      drugs. To assess the role of amygdaloid DA D(2) receptors in aversive
      emotionality, the D(2) receptor antagonist raclopride was infused into the
      amygdala prior to Pavlovian fear conditioning. Potentiated startle was used as a
      behavioral indicator of fear and anxiety. Classical fear conditioning and
      acoustic startle testing were conducted in a single session allowing for the
      concomitant assessment of shock reactivity with startle enhancement. Depending on
      dose, the results found conditioned fear acquisition and retention to be impaired
      following administration of raclopride into the amygdala. Additionally, the
      learning deficit was dissociated from shock detection and from fear expression
      assessed with the shock sensitization of acoustic startle. These findings further
      refine the known neural mechanisms of amygdala-based emotional learning and
      memory and were interpreted to suggest that, along with D(1) receptors, D(2)
      receptors in the amygdala may mediate the formation and the retention of newly
      acquired fear associations.

PMID- 11311884
TI  - Chronic variable stress and partial 5-HT denervation by parachloroamphetamine
      treatment in the rat: effects on behavior and monoamine neurochemistry.
AB  - Chronic variable stress (CVS) and manipulations of 5-HT-ergic neurotransmission
      are increasingly used as animal models of depression. In the present study, CVS
      for 2 weeks and a partial lesion of 5-HT projections by a small dose of
      parachloroamphetamine (PCA, 2 mg/kg) were applied independently or in
      combination. CVS reduced significantly the gain in body weight and increased the
      number of defecations in the open field test. PCA reduced body weight only within
      the first 24 h after its administration. Consumption of sucrose solution and its
      preference to water in non-deprived rats were significantly higher in PCA
      pretreated rats 2 weeks after CVS compared to control animals. In the forced
      swimming test, both PCA and CVS treatments reduced immobility on the first but
      not the second session. Both treatments reduced significantly the time rats spent
      in social interaction. CVS also elicited an increase in the weight of the right
      adrenal, but this effect was not present in the PCA-pretreated group. PCA reduced
      5-HT and 5-HIAA levels in the frontal cortex, hippocampus, and septum by
      approximately 20%. CVS increased HVA levels in the frontal cortex. Applied
      together, PCA pretreatment and CVS increased dopamine turnover in the frontal
      cortex. Conclusively, this study has provided evidence that chronic variable
      stress, which elicited expected physiological and neurochemical changes, does not
      reduce sucrose intake or preference in non-deprived animals, but, instead, may
      increase it after partial 5-HT-ergic denervation; and that partial 5-HT-ergic
      denervation by a low dose PCA treatment has a long-lasting effect on forced
      swimming and social behavior similar to chronic stress.

PMID- 11311885
TI  - Release of immunoreactive brain-derived neurotrophic factor in the spinal cord of
      the rat following sciatic nerve transection.
AB  - Using the antibody microprobe method, the sites of spinal release of
      immunoreactive brain-derived neurotrophic factor (BDNF) was studied in normal
      rats, and rats with prior sciatic nerve transection. In normal rats, a
      significant basal release of immunoreactive BDNF was found in the superficial
      dorsal horn. Following sciatic nerve transection (performed 14 days previously),
      release of BDNF was found throughout the whole of the dorsal horn, extending into
      deeper laminae. Electrical stimulation of the ipsilateral sciatic nerve at a
      strength adequate to excite either A fibres (20 Hz at 2x threshold voltage) or A
      and C fibres (2 Hz at 20x threshold voltage) did not alter the basal release of
      immunoreactive BDNF in normal or in nerve-injured rats. The results suggest that
      BDNF is released from the central terminals of primary afferent fibres, but such
      release is not solely dependent upon action potential invasion of these
      terminals. The increased extent of release following nerve transection is
      consistent with the hypothesis that BDNF plays a role in the central response to
      peripheral nerve injury.

PMID- 11311886
TI  - The kinetics of hypoxanthine efflux from the rat brain.
AB  - The brain efflux of radiolabelled hypoxanthine in the rat was rapid in the first
      minute after injection [K(eff)(i)=0.21+/-0.06 min(-1)], which was saturable with
      a V(max)=13.08+/-0.81 nM min(-1) g(-1), and a high K(m,app) (67.2+/-13.4 microM);
      the K(i,app) for inosine was 31.5+/-7.6 microM. Capillary depletion analysis
      indicated that hypoxanthine accumulates in neurons and glia with the time. From
      cross-inhibition studies with different purines and pyrimidines, it suggests that
      these molecules could also be important substrates for this carrier.

PMID- 11311887
TI  - Mechanically evoked perioral reflexes in premature and term human infants.
AB  - Neurophysiological assessment of the preterm human neonatal oromotor system has
      been limited due to their fragile medical state, and methodological limitations.
      A new, noninvasive technology known as the actifier was developed and used to
      evoke perioral motor unit activity during non-nutritive suck in preterm infants.
      A significant ontologic trend for the early component of the perioral reflex (R1)
      was discovered in the context of spontaneous, centrally-patterned oromotor
      behavior.

PMID- 11311888
TI  - Expression of corticotropin releasing factor, but not its binding protein, in CA1
      pyramidal cells of gerbil hippocampus following transient ischemia.
AB  - Recently, the ectopic expression of corticotropin-releasing factor (CRF) has been
      suggested as being associated with processes linked to neuronal injury and/or
      degeneration in response to a brain insult. However, there is little experimental
      data linking CRF directly to neuronal death induced by ischemia. Therefore, in
      the present study, we investigated the temporal and spatial alteration of CRF and
      its binding protein expressions in the hippocampus after transient ischemia. As a
      result, we found the selective increase of CRF immunoreactivity in the CA1
      pyramidal cells and their processes at only 4 days post-ischemic insult. In
      contrast, CRF binding protein immunoreactivity was rarely detected in the CA1
      region. These results suggest that transient ischemia may provoke selectively
      ectopic expression of CRF, but not of its binding protein, in vulnerable regions,
      and this enhancement of CRF may play important roles in the neurodegenerative
      process.

PMID- 11311889
TI  - Two paths for dissemination of Herpes simplex virus from infected trigeminal
      ganglion to the murine cornea.
AB  - Herpes simplex virus type 1 (HSV) was introduced into the mouse trigeminal
      ganglion by stereotaxic injection. We examined the form in which the virus was
      transported anterograde within axons and the spread of virus to glial and
      endoneurial cells of the nerve using EM immunocytochemistry. Our results indicate
      that viral dissemination in the trigeminal nerve may occur both within the axon
      and in the extracellular space of the endoneurium. HSV is intraaxonally
      transported at least in part as a nucleocapsid, i.e., with neither viral envelope
      nor additional cellular membranes. Schwann cells are infected as a result of
      spread in the endoneurium, as well as by nearby axons.

PMID- 11311890
TI  - beta-adrenergic receptor stimulation selectively inhibits IL-12p40 release in
      microglia.
AB  - The cytokine interleukin-12 (IL-12) is mainly produced in response to bacterial
      or parasitic infections. We examined the capacity of mouse brain microglia to
      release IL-12 forms upon challenge with bacterial lipopolysaccharide (LPS) and
      studied its modulation by sympathomimetics. LPS evoked the release of IL-12p40
      whereas the heterodimeric form, IL-12p70 was virtually undetectable.
      Sympathomimetics such as salbutamol dose-dependently inhibited IL-12p40 release,
      whereas the production of IL-6, TNFalpha and MIP-1alpha was only marginally
      influenced. The inhibitory effect of salbutamol could be abolished by beta
      antagonists, such as oxprenolol. The cAMP-elevating agent forskolin could mimic
      the effects of beta-agonists, indicating that IL-12p40 release inhibition
      involves intracellular cAMP accumulation. While microglial IL-12p40 may play a
      role in the regulation of IL-12p70 bioactivity, microglial release is itself
      modulated by IL-12p70. Recombinant IL-12p70 was found to enhance the LPS-evoked
      release of MIP-1alpha and to have a biphasic effect on both TNFalpha and MIP
      1alpha with release augmentation at lower and attenuation at higher doses.
      Finally, no functional correlation was found between the release of IL-12p40 and
      the induction of Kv1.3 potassium channels, another marker of microglial
      activation. Taken together, beta(2)-adrenoreceptor-mediated effects on microglial
      cyto- and chemokine release via cAMP accumulation could modulate inflammatory
      cascades during bacterial infections.

PMID- 11311891
TI  - Actions of the systemically active metabotropic glutamate antagonist MPEP on
      sensory responses of thalamic neurones.
AB  - It is known that metabotropic glutamate receptors of the subtypes mGlu1 and mGlu5
      participate in nociceptive processing in the thalamus, an area of prime
      importance in supra-spinal sensory processing. Antagonists of these receptors
      thus have potential as centrally-acting analgesics. We have investigated whether
      intravenous administration of the novel mGlu5-receptor antagonist 6-methyl-2
      (phenylethynyl)-pyridine (MPEP) is able to reduce nociceptive responses of
      thalamic neurones. Extracellular recordings were made from single thalamic
      neurones of adult male Wistar rats anaesthetised with urethane. MPEP (1 mg/kg)
      reduced neuronal responses to noxious thermal stimuli to a mean of 24+/-4% of
      control within 10 min, whereas saline injections had no significant effect.
      Partial recovery was seen within 30-45 min after injection. Responses of neurones
      to non-noxious stimuli were not significantly affected by MPEP administration. In
      addition, MPEP caused an increase in the power of the slow-wave component (<1 Hz)
      of the electroencephalogram (EEG), but had no significant effect on peak
      frequency of the EEG or on heart rate. These results confirm that nociceptive
      responses of thalamic neurones are mediated in part by mGlu5 receptors.
      Furthermore, the effectiveness of intravenous MPEP suggests that such antagonists
      may be useful as centrally-acting analgesics.

PMID- 11311892
TI  - Cell type-specific differences in the coupling of recombinant mGlu1alpha
      receptors to endogenous G protein sub-populations.
AB  - In this study the effects of cell background on the coupling of the type 1alpha
      metabotropic glutamate (mGlu1alpha) receptor to different G protein sub
      populations by recombinant expression of this receptor subtype in baby hamster
      kidney (BHK) and Chinese hamster ovary (CHO) cells have been investigated.
      Receptor-G protein interactions were assessed using [(35)S]GTPgammaS binding and
      subsequent Galpha subunit-specific immunoprecipitation. In a CHO cell line (CHO
      lac-mGlu1alpha), where mGlu1alpha receptor expression is under inducible control,
      stimulation of membranes with the mGlu receptor agonist quisqualate resulted in
      an increase in specific [(35)S]GTPgammaS binding to G(q/11)alpha only, whereas in
      a BHK cell line (BHK-mGlu1alpha) agonist stimulation increased [(35)S]GTPgammaS
      binding to G(q/11)alpha and also to pertussis toxin (PTx)-sensitive G(i/o)
      proteins (assessed using G(i1/2)alpha- and G(i3/o)alpha-specific antibodies).
      These data are consistent with our previous observations of dual, antagonistic
      G(q/11)/G(i/o) regulation of phospholipase C (PLC) in BHK-mGlu1alpha cells,
      whereas no evidence was found for a G(i/o) modulation of PLC activity in the CHO
      lac-mGlu1alpha cell line. PTx pre-treatment of either cell line had no effect on
      either the magnitude or the concentration-dependency of agonist-stimulated
      [(35)S]GTPgammaS-G(q/11)alpha binding, excluding the possibility that receptor
      G(i/o) uncoupling can unmask an increase in receptor-G(q/11) interaction.
      mGlu1alpha receptor expression per se had little effect on Galpha protein
      expression levels in either CHO or BHK cell lines, with the possible exception of
      a small, but consistent increase in G(o)alpha expression in BHK-mGlu1alpha cells
      compared to the vector-transfected control cell line (BHK-570). Semi-quantitative
      assessment of mGlu1alpha receptor immunoreactivity and [(3)H]quisqualate
      saturation binding analysis demonstrated a ca 10-fold higher mGlu1alpha receptor
      content in BHK cells. Whether the higher receptor expression level in BHK
      mGlu1alpha cells underlies the additional G(i/o) coupling observed in this cell
      line, or additional factors contribute to the phenomenon are discussed.

PMID- 11311893
TI  - 2-chloro-N(6)-cyclopentyladenosine-elicited attenuation of evoked glutamate
      release is not sufficient to give complete protection against pilocarpine-induced
      seizures in rats.
AB  - The effects of 2-chloro-N(6)-cyclopentyladenosine (CCPA) perfused
      intrahippocampally (1 microM) and injected intraperitoneally (0.5 mg/kg) were
      investigated in focally-evoked pilocarpine-induced (10 mM) seizures in freely
      moving rats. While the intrahippocampal perfusion of this highly selective
      adenosine A(1) receptor agonist gave complete protection against pilocarpine
      induced seizures, systemic administration only partially protected the animals,
      as evaluated by concomitant behavioural and electrocorticographical (ECoG)
      observations and monitoring of the neurotransmitter alterations. However,
      pilocarpine-evoked elevation of hippocampal glutamate overflow was significantly
      attenuated by CCPA irrespective of the mode of administration. Acute pretreatment
      with systemic 8-cyclopentyl-1,3-dipropylxanthine, a selective A(1) antagonist,
      reversed both the partial protective effect and the attenuating effect on the
      extracellular glutamate elicited by systemic CCPA administration.
      Intrahippocampal CCPA markedly reduced basal hippocampal dopamine efflux but not
      GABA or glutamate and considerably attenuated the pilocarpine-evoked elevation in
      dopamine levels. Systemic CCPA appeared to have little influence on the overall
      pattern of dopamine elevation. The findings give evidence that CCPA-elicited
      abatement of the evoked glutamate release alone, cannot fully account for its
      anticonvulsant effect and may suggest that the effects mediated by adenosine on
      postsynaptic adenosine receptors could be more crucial for its anticonvulsant
      effect.

PMID- 11311894
TI  - Unsulfated and sulfated neurosteroids differentially modulate the binding
      characteristics of various radioligands of GABA(A) receptors following chronic
      ethanol administration.
AB  - Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS)
      inhibited the binding of [(3)H]flunitrazepam (2 nM), [(3)H]muscimol (5 nM) and 4
      nM [(35)S]t-butylbicyclophosphorothionate [(35)S]TBPS in the rat cerebellum as
      well as cerebral cortex. DHEAS-induced inhibition of binding of these
      radioligands (62% to 100%) was more pronounced as compared to that in the case of
      DHEA (5% to 31%). DHEAS, unlike DHEA, inhibited [(3)H]flunitrazepam binding
      significantly to a lesser extent in the cerebellum of ethanol-dependent rats as
      compared to the control group (I(max):82+/-1vs.92+/-2%, p<0.005). However, DHEA,
      unlike DHEAS, inhibited [(35)S]TBPS binding to a greater extent in the ethanol
      dependent rat cerebellum as compared to the control group (I(max):31+/-2vs.19+/
      2%, p<0.005). Furthermore, DHEA was more potent in inhibiting [(35)S]TBPS binding
      in the cerebellum (IC(50):55+/-5 vs. 74+/-7 microM, p<0.05) and cerebral cortex
      (IC(50):26+/-4vs.64+/-9 microM, p<0.05) of ethanol-dependent rats as compared to
      the control group. These observations indicate that unsulfated and sulfated
      androstane-steroids modulate the GABA(A) receptors in the control as well as the
      ethanol-dependent rats differentially, and also suggest that the androstane
      steroid binding sites associated with the GABA(A) receptors play an important
      role during ethanol dependence.

PMID- 11311895
TI  - Both GABA(B) receptor agonist and antagonists decreased brain stimulation reward
      in the rat.
AB  - The present experiments were designed to determine the role of GABA(B) receptor
      function on brain stimulation reward. Using a discrete-trial current-intensity
      threshold procedure, dose-effect functions were generated for the GABA(B)
      receptor agonist CGP 44532 (0-1.0 mg/kg, s.c.) and the GABA(B) receptor
      antagonists CGP 56433A (0-10.0 mg/kg, s.c.) and CGP 51176 (0-300.0 mg/kg, s.c.)
      on brain reward thresholds in rats. The GABA(B) receptor antagonists CGP 56433A
      and CGP 51176 were used also to examine interaction effects with the GABA(B)
      receptor agonist CGP 44532 on reward thresholds. Administration of the highest
      doses of both the GABA(B) receptor agonist and antagonists elevated reward
      thresholds. Thus, both the agonist and antagonists used induced a reward
      decrement when administered separately. In addition, the co-administration of
      either of the two receptor antagonists with the agonist induced an additive
      effect on thresholds, rather than blocking the agonist-induced threshold
      elevations. These results suggest that activation of GABA(B) receptors modulates
      intracranial self-stimulation behavior in a complex fashion, possibly through
      differential effects of GABA(B) agonists and antagonists on pre- and post
      synaptic GABA(B) receptors.

PMID- 11311896
TI  - Regulation of phospholipase Cbeta activity by muscarinic acetylcholine and 5
      HT(2) receptors in crude and synaptosomal membranes from human cerebral cortex.
AB  - Stimulation of phospholipase Cbeta by receptor agonists and G proteins has been
      characterized in crude cerebral membrane preparations, but little is known about
      their presynaptic localizations and little information is currently available for
      human brain tissue. The characteristics of phosphoplipase C transmembrane
      signaling were studied in crude and synaptosomal plasma membranes from postmortem
      human prefrontal cortex by measuring the hydrolysis of exogenous
      [(3)H]phosphatidylinositol4,5bisphosphate(PIP(2)) and the immunoreactive levels
      of phospholipase C (PLC) and G(alphaq/11) proteins. Regulation of PLC activity by
      Ca(2+) and the 5-HT(2) receptor agonist 5-methyltryptamine, but not by guanosine
      5'-O-[3-thiotriphosphate] and the muscarinic acetylcholine receptor agonist
      carbachol were different between crude and synaptosomal membranes. KCl (20 mM)
      stimulation was absent in both preparations. Levels of G(alphaq/11)-protein
      subunits differed between preparations. The functional inhibition carried out
      with pirenzepine in crude membranes in order to reverse the carbachol-induced PLC
      stimulation indicates the existence of a component (53%) of the response that is
      activated by the M(1) muscarinic acetylcholine receptor subtype, and another
      component (47%) probably mediated by the M(3) muscarinic acetylcholine receptor
      subtype. In synaptosomal plasma membranes an increased inhibition of carbachol
      induced PLC activation through M(1) was found. The PLC activation by 5
      methyltryptamine (ketanserin-sensitive in crude membranes) was absent in
      synaptosomal plasma membranes suggesting the lack of activity mediated by 5-HT(2)
      serotonin receptors.

PMID- 11311897
TI  - Responses of rat spinal neurons to distension of inflamed colon: role of
      tachykinin NK2 receptors.
AB  - Tachykinin NK2 receptors are implicated in nociception and the control of
      intestinal motility. Here we examined their involvement in responses of spinal
      lumbosacral neurons with colon input to distension of normal or inflamed colon in
      anesthetized rats. The responses of single neurons to colorectal distension (5-80
      mmHg), to electrical stimulation of the pelvic nerve (bypassing sensory
      receptors) and to somatic stimulation were characterized. The effect of
      cumulative doses of an NK2 receptor antagonist, MEN 11420 (10-1000 microg kg(-1)
      IV), on responses to these stimuli was tested in control conditions (n=6), or 45
      min after intracolonic instillation of acetic acid (n=6). After colonic
      inflammation, neuronal responses to colorectal distension and pelvic nerve
      stimulation were significantly greater. MEN 11420 dose-dependently inhibited the
      enhanced responses to colorectal distension after inflammation (ID50=402+/-14
      microg kg(-1)), but had no significant effect on responses to pelvic nerve
      stimulation or distension of the normal colon, suggesting a peripheral action
      selective for the inflamed colon. We conclude that MEN 11420 possesses peripheral
      anti-hyperalgesic effects on neuronal responses to colorectal distension. These
      results provide a neurophysiological basis for a possible use of tachykinin NK2
      receptor antagonists in treating abdominal pain in irritable bowel syndrome
      patients.

PMID- 11311898
TI  - Tetrahydrocannabinol-induced apoptosis of cultured cortical neurones is
      associated with cytochrome c release and caspase-3 activation.
AB  - Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive component of
      marijuana, is associated with impaired cognition and altered cortical function.
      THC transduces its central effects via activation of the G-protein linked
      cannabinoid receptor CB1. In this study we report that THC induces morphological
      degenerative changes in cultured cortical neurones, such as membrane blebbing and
      formation of apoptotic bodies, that are consistent with the apoptotic pathway of
      cell death. The THC-induced apoptosis was blocked by the CB1 receptor antagonist
      AM251 and pertussis toxin (PTX), suggesting that this effect of THC involves
      receptor-mediated activation of the G-protein subtypes G(i) or G(o). THC also
      promoted translocation of mitochondrial cytochrome c to the cytosol and increased
      the activity of the cysteine protease caspase-3, in a PTX-sensitive manner. The
      results from this study suggest that coupling of THC to a PTX-sensitive G-protein
      promotes cytochrome c release, caspase-3 activation and subsequent degeneration
      of cultured cortical neurones. This apoptotic pathway may underlie the
      compromised neuronal function that is associated with marijuana usage.

PMID- 11311899
TI  - Tolerance to midazolam's anxiolytic effects after short-term nicotine treatment.
AB  - In the social interaction test of anxiety, microinjections of midazolam (2-8
      microg) into the dorsal hippocampus or dorsal raphe nucleus significantly
      increased the time spent in active social interaction, without changing locomotor
      activity, thus indicating specific anxiolytic effects. However, tolerance
      developed to these effects in rats that had been pre-treated for 6 days with (-)
      nicotine (0.1 mg/kg/day; subcutaneous). Thus, cross-tolerance to the anxiolytic
      effects of midazolam develops rapidly following a short period of treatment with
      a low dose of nicotine, which contrasts with the more slowly developing tolerance
      (about 3 weeks) that develops after benzodiazepine treatment. Following 6 days of
      nicotine treatment there was a significant reduction in [(3)H]flunitrazepam
      binding at 2 and 10 nM in the hippocampus, but no change in the midbrain. The
      decrease in benzodiazepine binding could explain tolerance to the effects of
      midazolam when administered to the dorsal hippocampus, but other mechanisms, such
      as indirect effects on the serotonergic (5-HT) system, might be involved in
      tolerance to the effects of dorsal raphe nucleus administration.

PMID- 11311900
TI  - The acute effects of zolpidem compared to diazepam and lorazepam using
      radiotelemetry.
AB  - The present study used a radiotelemetric method to compare the muscle relaxant,
      hypothermic and locomotor depressant actions of the imidazopyridine zolpidem,
      with those of the benzodiazepines lorazepam and diazepam. Rats, n=7 per group,
      were divided into 3 dose-dependent treatment groups (highest, middle, and
      lowest). Each rat within a treatment group received a single dose of diazepam,
      lorazepam, zolpidem and vehicle. All three drugs induced dose-dependent decreases
      in body temperature, locomotor activity and electromyographic (EMG) activity.
      Administration of zolpidem (5 and 10 mg/kg) resulted in maximal decrements in
      locomotor activity that were comparable to those elicited by both diazepam (10
      and 20 mg/kg) and lorazepam (12.5 and 25 mg/kg). Zolpidem (10 mg/kg) decreased
      EMG activity levels to approximately 45% of vehicle treated controls; a value
      similar to that induced by diazepam (2.5 mg/kg). These data suggest that the
      imidazopyridine zolpidem has a similar profile of acute effects in comparison to
      the benzodiazepines diazepam and lorazepam. However, the relative magnitude of
      the effects differed, with zolpidem producing less hypothermia and muscle
      relaxation than the two benzodiazepines.

PMID- 11311901
TI  - Distinct regional distribution of human equilibrative nucleoside transporter
      proteins 1 and 2 (hENT1 and hENT2) in the central nervous system.
AB  - Nucleoside transport processes play an important role in human cells in salvage
      of nucleosides used in the biosynthesis of nucleic acids and in regulating
      endogenous adenosine concentrations in the human central nervous system (CNS). By
      altering the levels of adenosine available to interact with cell-surface
      receptors, nucleoside transporters have profound effects on the ability of
      adenosine to modulate neurotransmission, vascular tone and other physiological
      events. Although the human equilibrative nucleoside transporters 1 and 2 (hENT1
      and hENT2) are believed to play a crucial role in modulating brain function,
      their distribution within the major divisions of the human CNS is not known. In
      this work, antibodies specific for hENT1 and hENT2 were produced against
      fragments of the transporter proteins and used for immunoblot analysis of
      enriched membrane fractions prepared from several regions of the human brain.
      While hENT1 was most prevalent in the frontal and parietal lobes of the cerebral
      cortex, thalamus, midbrain and basal ganglia, hENT2 was concentrated in the
      cerebellum and brainstem regions, particularly the pons. The apparent reciprocal
      distribution of hENT1 and hENT2 in human brain suggests that these nucleoside
      transporter proteins are produced in distinct regions of the CNS where they
      function in nucleoside salvage and/or regulation of exogenous adenosine. Within
      the brain regions that were investigated, the pattern of hENT1 distribution
      correlated well with adenosine A(1) receptor abundance. The regional co
      localization of hENT1 and A(1) receptor protein suggests an important role of
      hENT1-mediated transport process in the control of neuromodulatory actions
      mediated by adenosine A(1) receptors in human brain.

PMID- 11311902
TI  - Anticonvulsant activity of 3,4-dicarboxyphenylglycines in DBA/2 mice.
AB  - The 3,4-dicarboxyphenylglycines (3,4-DCPG) inhibit sound-induced seizures in
      DBA/2 mice with the racemate being notably more potent than either isomer (ED(50)
      (nmol, i.c.v.)): (RS)-3,4-DCPG (0.004; 86 mg/kg, i.p.)>>the mGlu(8) agonist (S)
      3,4-DCPG (0.11)>the AMPA antagonist (R)-3,4-DCPG (0.38). A potentiation of
      anticonvulsant activity between AMPA and mGlu(8) receptors was confirmed by
      combining (R)-3,4-DCPG with the mGlu(8) agonist (RS)-4-phosphonophenylglycine.
      This potentiating mechanism provides a novel strategy for the treatment of
      epileptic seizures.

PMID- 11311904
TI  - Clinical features of late-onset idiopathic aqueductal stenosis.
AB  - BACKGROUND: Although late-onset idiopathic aqueductal stenosis (LIAS) is
      considered a good indication for endoscopic third ventriculostomy (ETV), the
      characteristics of this clinical entity have seldom been reported in the magnetic
      resonance (MR) imaging era. The authors reviewed their patients with LIAS who
      were treated by ETV to confirm its clinical features and response to treatment.
      METHODS: The study group was composed of 31 patients diagnosed with LIAS who were
      previously untreated. Both anatomic and cine phase-contrast MR studies were used
      to detect the obstruction of the aqueduct canal. The preoperative symptoms were
      statistically analyzed in relation to the age of the patients and the degree of
      preoperative ventriculomegaly. RESULTS: The overall success rate of ETV was 83.9%
      with mean follow-up duration of 26.2 months. Only two patients had acute onset
      (within one month) without any predisposing chronic symptoms. The patients with
      chronic symptoms (longer than 6 months [n = 25]) can be divided into two major
      groups: a headache group (n = 12) and a normal pressure hydrocephalus (NPH)
      symptom group (n = 11), Two patients had both headaches and NPH symptoms. The
      patients in the headache group were significantly younger and had smaller
      ventricles than the patients in the NPH group. With multivariate regression
      analysis, age independently affected the type of chronic symptoms. CONCLUSIONS:
      LIAS typically presents with chronic onset, with younger patients tending to have
      headaches, and older patients tending to have NPH symptoms. ETV is considered the
      best surgical option, with more than an 80% success rate.

PMID- 11311906
TI  - Clinical outcomes of aneurysmal subarachnoid hemorrhage patients treated with
      oral diltiazem and limited intensive care management.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) patients are frequently
      treated with prophylactic nimodipine and undergo invasive monitoring of blood
      pressure and volume status in an intensive care unit (ICU) setting to decrease
      the incidence of delayed ischemic neurological deficit (DIND) and improve
      functional outcomes. The goal of this study was to examine the incidence of DIND
      and poor functional outcomes in a consecutive series of SAH patients treated with
      a different regimen of prophylactic oral diltiazem and limited use of intensive
      care monitoring. METHODS: The study involved a consecutive series of 123
      aneurysmal SAH patients treated by the senior author who were admitted within 72
      hours of hemorrhage and who never received nimodipine or nicardipine. Functional
      outcomes were graded using the Glasgow Outcome Scale (GOS). RESULTS: Of the 123
      patients identified, favorable outcomes (GOS 4 and 5) were achieved in 74.8%. The
      incidence of DIND was 19.5%. Hypertensive, hypervolemic, hemodilutional (HHH)
      therapy was used in 10 patients (8.1%) and no patients were treated for DIND by
      endovascular means. Seven patients (5.7%) had a poor functional outcome or death
      because of DIND and two of these were related to complications of HHH therapy.
      These results were compared to contemporary series of SAH patients managed with
      other treatment protocols. CONCLUSIONS: Functional outcomes of patients treated
      with a regimen of oral diltiazem, limited use of ICU monitoring and HHH therapy
      for DIND compare favorably with other contemporary series of SAH patients.

PMID- 11311909
TI  - Characteristics of aneurysms arising from the horizontal portion of the anterior
      cerebral artery.
AB  - BACKGROUND: Aneurysms arising from the proximal portion of the anterior cerebral
      artery (A1: horizontal portion) are quite rare and are considered to be unique,
      because they are usually connected with other vascular anomalies and are
      sometimes part of a multiple aneurysm occurrence. A1 aneurysm cases experienced
      over the past seven and a half years are summarized in this paper. METHODS: A
      total of 413 patients were surgically treated including 142 patients with
      subarachnoid hemorrhage (SAH); the remaining 271 patients had unruptured
      aneurysms. Among them, nine cases were categorized as constituent A1 aneurysms,
      three with SAH and six with unruptured aneurysms. RESULTS: The shape of the
      aneurysm was saccular in all nine cases. Three of the nine cases had associated
      vascular malformations. The average aneurysm diameter in the three cases with SAH
      was 4.0 mm, which is smaller than other common aneurysms presenting with SAH.
      Eight aneurysms developed at the takeoff point of perforating arteries-the medial
      lenticulostriate artery in five cases and the recurrent artery of Heubner in
      three cases. In the remaining case, the aneurysm originated from the proximal end
      of the associated A1 fenestration. All nine patients had an excellent outcome
      after surgery. CONCLUSION: A1 aneurysms require surgical elimination even if they
      are small. We emphasize the importance of preserving the blood flow of these
      perforating arteries by avoiding compression with either the clip blade or the
      clip body itself.

PMID- 11311913
TI  - Spontaneous cerebellar hemorrhage: clinical remarks on 50 cases.
AB  - BACKGROUND: Only during the past 10 years have spontaneous cerebellar hemorrhages
      became a well-defined nosological entity. The surgical indication remains
      debatable. Our primary objective in this study was to set the criteria for
      undertaking surgery by determining the critical diameter of the hematoma and
      considering the patients' neurological status (Glasgow Coma Scale). METHODS:
      During the 8-year period 1990 through 1997 a series of 50 consecutive patients
      with spontaneous cerebellar hemorrhage were admitted to the Emergency
      Neurosurgery Unit, University of Rome "La Sapienza" (Italy). On admission all
      patients underwent a standard neurological examination, (Glasgow Coma Scale) and
      a computed tomographic scan. The diameter and the site of the hematoma, a
      coexisting tight posterior fossa, and the presence of hypertensive hydrocephalus
      were the criteria, in association with the patients' neurological status, used as
      indications for surgery. RESULTS: Operative mortality was nil; and perioperative
      mortality eight patients (16%, increasing to 24% including the four patients who
      were deeply comatose on admission). Most patients who died (seven of eight) had
      two or more general medical risk factors (arterial hypertension and diabetes
      mellitus; arterial hypertension and liver disease; or liver disease and
      hematological disorders). CONCLUSION: In patients presenting with spontaneous
      cerebellar hemorrhage the essential criteria indicating surgery are a hematoma 40
      mm x 30 mm on CT imaging in the cerebellar hemisphere or 35 mm x 25 mm on CT
      imaging in the vermis, the presence of a tight posterior fossa (critical size
      reduced by 10 mm), and a Glasgow Coma Score less than 13.

PMID- 11311915
TI  - Primitive cerebral melanoma: case report and review of the literature.
AB  - BACKGROUND: Central nervous system primary malignant melanoma accounts for
      approximately 1% of all the cases of melanoma; reports in the literature are
      relatively rare. CASE DESCRIPTION: A 74-year-old man was hospitalized because of
      an episode of aphasia. The neuroradiologic examinations demonstrated a round
      homogeneous lesion extending near the left sylvian fissure. He had no
      extracranial abnormalities. The patient underwent a neurosurgical procedure and
      the tumor was macroscopically totally excised. Pathological examination of the
      surgical specimen revealed a histological appearance similar to that of melanoma.
      A diagnosis of primary CNS melanoma was made after careful dermatologic and
      ophthalmologic examination, which ruled out presence of cutaneous or choroidal
      melanoma. The patient did not receive any further treatment and he is free of
      disease 2 years after diagnosis. CONCLUSIONS: We report a case of primary
      cerebral melanoma of the left temporal lobe; clinical, neuroradiological, and
      histological findings are discussed with review of the literature. Primary
      melanoma of the CNS may present either with localized intra/extra-axial mass
      lesions or with meningeal spread, which carries a worse prognosis. The prognosis
      of cerebral primitive melanoma is variable, although it is common opinion that
      primitive cerebral melanoma has a better prognosis than cutaneous melanoma, with
      two cases in the literature surviving 9 and 12 years.

PMID- 11311917
TI  - Cavernous hemangioma of the sphenoid sinus: case report and review of the
      literature.
AB  - BACKGROUND: Few cases of paranasal sinus cavernous hemangiomas have been reported
      in the literature. We report the first case of cavernous hemangioma of the
      sphenoid sinus and discuss therapeutic considerations and differential diagnosis.
      CASE DESCRIPTION: A case of sphenoid sinus tumor in a 67-year-old woman is
      reported. The initial symptoms were a horizontal diplopia, a left facial
      dysesthesia, and a recent history of unusual headache. Physical examination
      revealed a left VIth nerve paresis. A CT scan was performed showing a hypodense
      homogeneous mass in the sphenoid sinus that was not enhanced after administration
      of contrast medium. MR study demonstrated on T1-weighted image an isointense
      nonenhancing homogeneous mass filling the sphenoid sinus. On T2-weighted images
      the tumor mass displayed a mild hyperintense signal. The patient was operated on
      via a transsphenoidal approach with total removal of the tumor. Pathological
      findings were consistent with a nonosseous cavernous hemangioma. MR imaging
      performed 5 years later was still normal. CONCLUSION: The clinicoradiological and
      pathological features of this entity are described, and the literature reviewed.

PMID- 11311919
TI  - Parafalcine chondrosarcoma: an unusual localization for a classical variant. Case
      report and review of the literature.
AB  - BACKGROUND: Intracranial chondroid tumors are infrequently seen in neurosurgical
      practice. These tumors usually arise from cartilaginous synchondroses at the base
      of the skull, but occasionally from the pluripotential mesenchymal cells of the
      meninges. We present here a case of classic low-grade giant chondrosarcoma of the
      falx cerebri. This is only the second case of this variant reported in this
      location, and we summarize the diagnostic criteria with a brief review of
      literature. CASE REPORT: A 56-year-old female patient was admitted to the
      hospital with a history of progressive right-sided weakness occurring in the last
      8 months and a recent grand mal seizure. Radiological evaluation demonstrated a
      large extra-axial mass in the left parafalcine area, suggesting a possible
      meningioma. An anterior interhemispheric approach enabled gross total removal of
      the tumor and a histologic diagnosis of a low-grade classic chondrosarcoma was
      made. The patient is currently stable and has shown no evidence of recurrence in
      more than 3 years without any adjuvant treatment. CONCLUSIONS: Intracranial
      cartilaginous tumors include classical, mesenchymal and myxoid chondrosarcomas in
      addition to benign chondromas. Parafalcine localization should be considered for
      all these variants as well as for meningiomas, hemangiopericytomas, solitary
      fibrous tumors, and meningeal metastatic carcinomas. Detailed radiological
      evaluation, light microscopic and ultrastructural analyses, and
      immunocytochemistry are essential for correct diagnosis. In contrast to
      mesenchymal and myxoid types, the prognosis of classic variants is usually good
      and does not require adjuvant treatment modalities if a radical resection of the
      tumor can be obtained. Increased documentation of clinical, radiological, and
      histologic findings as well as response to treatment modalities will provide a
      better understanding of the pathophysiology of these rare tumors, and highlight
      the optimum treatment strategies

PMID- 11311922
TI  - Thoughts of a young European neurosurgeon.

PMID- 11311920
TI  - Ectopic arachnoid granulomatosis: a case report.
AB  - BACKGROUND: Arachnoid granulation can sometimes show hypertrophy, developing
      extensively apart from the venous sinus, and in that case, a differential
      diagnosis should be made between this granulation and tumors. In this case, we
      hypothesized that cerebrospinal fluid was absorbed in the region of abnormal
      stains revealed by angiography. CASE DESCRIPTION: A 67-year-old female with
      headache was admitted to our hospital. A plain radiograph revealed accumulated
      numerous osteolytic lesions in the right frontal bone. T1-weighted magnetic
      resonance (MR) images demonstrated mixed-intensity lesions. On the T2-weighted MR
      images, we observed that the lesions were mixed, with areas of the same
      intensities as gray matter and cerebrospinal fluid. An abnormal vascular stain
      from the frontal branch of the middle meningeal artery was confirmed. After a
      craniotomy, numerous white granular masses were observed. These masses had
      penetrated the dura mater and adhered rigidly to the arachnoid membrane.
      Histological examination revealed them to be normal arachnoid granulations and
      villi. CONCLUSION: This case was diagnosed as an ectopic arachnoid
      granulomatosis. No case report has previously been published describing numerous
      arachnoid granulations away from the venous sinuses.

PMID- 11311923
TI  - Association study of CAG repeats in the KCNN3 gene in Japanese patients with
      schizophrenia, schizoaffective disorder and bipolar disorder.
AB  - To investigate a possible involvement of expanded triplet repeats of genome in
      the genomes of patients with endogenous psychoses, we examined a CAG repeat
      polymorphism in the coding region of the KCNN3 gene in schizophrenia,
      schizoaffective disorder, bipolar disorder and controls of the Japanese
      population. There were no significant differences in the CAG repeat number of
      longer or shorter alleles among the four diagnostic groups or among the
      schizophrenia hebephrenic and paranoid subtypes.

PMID- 11311924
TI  - Poor performance in smooth pursuit and antisaccadic eye-movement tasks in healthy
      siblings of patients with schizophrenia.
AB  - This study examines the area of eye movement dysfunctions as an indicator of
      vulnerability to schizophrenia. Eye movement performance was investigated with
      three different paradigms: Smooth Pursuit Eye Movements (SPEM); Visually Guided
      Saccades (VGS); and Antisaccades (AS) in 21 clinically stable patients with
      schizophrenia, 21 of their healthy, biological full siblings and 21 healthy
      control subjects. The three groups did not differ on VGS performance, whereas
      both patients and their siblings showed lower SPEM gain, an increased catch-up
      Saccades (CUS) rate, reduced AS accuracy and an increased number of AS errors in
      comparison to control subjects. In addition, patients with schizophrenia
      exhibited increased AS latency. Among the patients with schizophrenia, eye
      movement abnormalities did not correlate with age, gender, clinical state or
      duration of illness. These data suggest that abnormalities of SPEM and AS may
      represent neurobiological markers of the vulnerability to schizophrenia in
      individuals at high genetic risk for the disease.

PMID- 11311925
TI  - Gating of the vertex somatosensory and auditory evoked potential P50 and the
      correlation to skin conductance orienting response in healthy men.
AB  - A defect in auditory evoked potential (AEP) P50 gating supports the theory of
      information-processing deficits in schizophrenia. The relationship between gating
      of the mid-latency evoked potentials (EP) in the somatosensory and the auditory
      modalities has not been studied together before. In schizophrenia, we might
      expect the processing deficits to act on multiple modalities. We have examined
      the gating of median nerve somatosensory EP (SEP) following paired stimulation
      identical to the AEP P50 gating paradigm using interstimulus intervals (ISI) of
      500, 750 and 1000 ms and the correlation of gating to the skin conductance
      orienting response (SCOR) in 20 healthy men. We measured mid-latency vertex
      components (SEP: P50, N65, P85 and N100; AEP: P30, N45, P50 and N80). The gating
      was most pronounced at ISI 500 ms where the SEP P50 and N100 gating were 0.59 and
      0.37, respectively, as compared to a gating of 0.61 in P30, 0.33 in P50 and 0.45
      in N80 in the AEP. Repetition effects in the two modalities were not correlated.
      AEP P50 gating was correlated to skin conductance level (SCL). The combination of
      recording repetition effects on the mid-latency EP in two modalities could
      provide a method for investigating if deficits of information processing in
      schizophrenia are cross-modal.

PMID- 11311926
TI  - Effect of medroxyprogesterone pretreatment on pentagastrin-induced panic symptoms
      in females with panic disorder.
AB  - Clinical observation, as well as epidemiological and research data, suggest that
      female gonadal hormones influence the course of panic disorder (PD). Panicogenic
      agents such as pentagastrin are useful tools with which to study the
      pathophysiology of panic attacks. Nine women with PD were randomly assigned to
      receive, in a crossover design, a 3-day pretreatment with medroxyprogesterone
      acetate (MP) prior to an injection of pentagastrin, and a 3-day pretreatment with
      a placebo prior to another injection of pentagastrin. The panic response and the
      anxiety response to pentagastrin were decreased after MP pretreatment. These
      preliminary results support the use of laboratory models for investigations of
      the interactions between progestins and anxiety.

PMID- 11311927
TI  - Serum cholesterol, suicidal behavior and impulsivity in cocaine-dependent
      patients.
AB  - Relationships between serum cholesterol and suicidal behavior have been reported.
      As suicidal behavior is common in cocaine dependence, we looked for a
      relationship with serum cholesterol. To do this, we compared 57 cocaine-dependent
      patients who had attempted suicide with 111 cocaine-dependent patients who had
      never attempted suicide for their admission total serum cholesterol levels. We
      found that there were no significant differences between cocaine-dependent
      patients who had or had not attempted suicide in their total serum cholesterol
      levels. Also, there were no significant correlations between total serum
      cholesterol levels and scores on the Barratt Impulsivity Scale. Thus, admission
      total serum cholesterol does not appear to be clinically useful in the assessment
      of suicidal behavior in cocaine-dependent patients.

PMID- 11311928
TI  - The contrasting influence of depressive and hyperthymic temperaments on
      psychometrically derived manic subtypes.
AB  - The present investigation focused on symptomatological subtypes of mania and
      their relationships with affective temperaments and other clinical features of
      bipolar disorder. In 153 inpatients with mania diagnosed according to DSM-III-R,
      symptomatological subtypes have been investigated by means of principal component
      factor analysis of 18 selected items of the Comprehensive Psychopathological
      Rating Scale (CPRS). We compared other clinical features, depressive and
      hyperthymic temperamental attributes, and first degree-family history for mood
      disorders among the various manic subtypes on the basis of the highest z-scores
      obtained on each CPRS factor (dominant CPRS factor groups). Five factors-
      Depressive, Irritable-Agitated, Euphoric-Grandiose, Accelerated-Sleepless,
      Paranoid-Anxious--emerged, accounting for 59.8% of the total variance. When the
      factor-based groups were compared, significant differences emerged in terms of
      the duration of the current episodes, rates of chronicity and incongruent
      psychotic features--being highest in the 'Depressive' and 'Paranoid-Anxious'
      dominant groups. The patients with highest z-scores for the 'Euphoric-Grandiose',
      'Paranoid-Anxious' and 'Accelerated-Sleepless' factors were those most likely to
      belong to the hyperthymic temperament, while the 'Depressive' dominant group had
      the highest rate of depressive temperament. Finally, it is noteworthy that the
      'Irritable-Agitated' group was high for both temperaments. The foregoing
      multidimensional structure of mania--revealing five factors--is generally
      concordant with the emerging literature. Consistently with our original
      hypothesis, a hyperthymic temperament seems to underlie the most extreme manic
      excitement with euphoric-accelerated-paranoid phenomenology. By contrast, the
      depressive temperament seemed to mute the expression of mania into a depressive
      manic phenomenology.

PMID- 11311929
TI  - Validation of the Interview Module for Intermittent Explosive Disorder (M-IED) in
      children and adolescents: a pilot study.
AB  - We identified a subset of impulsive, aggressive children as having symptoms that
      met criteria for Intermittent Explosive Disorder (IED) using the Interview Module
      for Intermittent Explosive Disorder (M-IED). The M-IED was administered to 34
      children and adolescents between the ages of 10 and 17. These data provide
      initial evidence for the M-IED as a useful instrument in the diagnosis of IED in
      adolescents. The M-IED displayed a high level of inter-rater reliability and
      adequate test-retest reliability. Construct validity was supported by the fact
      that the subjects with IED symptomatology had significantly more lifetime
      aggression, oppositionality, inattention and hyperactivity/impulsivity compared
      to community controls. In addition, the subjects with IED symptomatology had a
      significantly greater number of episodes of lifetime physical aggression and
      documented episodes of aggression while in residential treatment compared to
      psychiatric controls. The subjects with IED symptomatology had a greater number
      of positive screening questions for DSM-IV diagnoses using the Swanson, Nolan and
      Pelham questionnaire (SNAP-IV), particularly those related to IED and
      posttraumatic stress disorder than psychiatric controls.

PMID- 11311930
TI  - Factors affecting reliability and confidence of DSM-III-R psychosis-related
      diagnosis.
AB  - The relationships between interrater diagnostic reliability, confidence in
      diagnosis, DSM-III-R criteria ambiguity and case report data quality were
      examined in 20 case vignettes describing psychosis-related symptomatology. Each
      of seven diagnosticians made DSM-III-R diagnoses and gave confidence ratings for
      those diagnoses, as well as ratings on quality of data presented and clarity of
      diagnostic criteria for each vignette. As hypothesized, confidence ratings
      significantly predicted interrater diagnostic agreement. Clarity of DSM-III-R
      criteria positively correlated with both interrater reliability and confidence.
      Case report data quality correlated with diagnostic confidence but, contrary to
      the authors' hypothesis, did not correlate with interrater agreement. The authors
      conclude that confidence ratings may be useful indices of diagnostic reliability
      among experienced clinicians and suggest that the case report method allows for
      reliable diagnoses to be made.

PMID- 11311931
TI  - Estimating the consequences of anti-psychotic induced weight gain on health and
      mortality rate.
AB  - Many anti-psychotic medications produce marked weight gain. In this study, we
      estimate the expected impact of degrees of antipsychotic-induced weight gain on
      selected mortality rate and incidence rates of impaired glucose tolerance (IGT)
      and hypertension (HTN) among US adults. Using raw data from 5209 respondents from
      the Framingham Heart Study's public use data set and national statistics on
      population demographics, we estimated the expected effect of weight gain on
      number of deaths and incident cases of IGT and HTN for a 10-year period
      commencing in 1999. Results indicated that the estimated deleterious effects of
      weight gain were greater for people with higher BMIs at baseline, for greater
      degrees of weight gain, for men than women, and for older than younger persons.
      Because there is a 'U-shaped' relation between BMI and mortality rate, small to
      moderate weight gains among people with baseline BMIs less than 23 were predicted
      to decrease mortality rates, whereas weight gains among people with baseline BMIs
      above that level were expected to increase mortality rates. However, the
      relations of IGT and HTN with BMI are monotonically increasing. Thus, the
      anticipated effect of weight gain on IGT and HTN is deleterious regardless of
      baseline BMI. Because it is unclear whether the beneficial effects of the
      atypical agents on, for example, reducing suicide mortality, outweigh the
      putative increase in mortality due to weight gain, we estimate the beneficial
      effects due to decreased death from suicide with the potential deleterious
      effects due to a 10-kg weight gain. We found that 492 suicide deaths per 100,000
      schizophrenic patients would be prevented over 10 years with the use of clozapine
      compared to 416 additional deaths due to antipsychotic induced weight gain.
      Although this estimate is rather crude and should be seen only as offering a
      sense of the likely situation, results suggest that the lives saved via clozapine
      may essentially be offset by the deaths due to weight gain. As we discuss, it is
      not possible to provide definitive estimates of the effect of antipsychotic
      induced weight gain on health and mortality, but our findings suggest that the
      magnitude of weight gains induced by many antipsychotic agents is likely to have
      important deleterious effects on mortality and health.

PMID- 11311932
TI  - Specific body image pathology in acute schizophrenia.
AB  - Despite a wide phenomenological interest in body image pathology in
      schizophrenia, there has been little systematic empirical research. This study
      aimed at establishing the specificity of body image pathology in patients with
      schizophrenia, its changes during acute treatment, and its association with other
      symptom factors. Cognitive (thoughts/beliefs regarding the body--body concept),
      affective (body satisfaction--body cathexis) and perceptual (body size estimation
      -body schema) facets of body image and psychopathology were assessed in in
      patients with paranoid schizophrenia (N = 60), schizoaffective disorder (N = 19),
      depressive disorder (N = 40) and anxiety disorder (N = 28) at admission, and
      after 2 and 4 weeks of treatment. Body size perception was also assessed in a
      sample of healthy subjects (N = 44). Patients with paranoid
      schizophrenia/schizoaffective disorder showed under-estimation of lower
      extremities at each time point. They expressed a higher degree of body concept
      disturbances at admission, but not at later stages. In a factor analysis, body
      perception and body concept loaded on distinct factors, which were separate from
      positive symptoms, negative symptoms, and anxiety. Patients with acute paranoid
      schizophrenia and schizoaffective disorder seem to have a specific and consistent
      disturbance of body size perception, which might indicate a dysfunction of
      sensory information processing.

PMID- 11311933
TI  - Fruit-developmental regulation of bell pepper knolle gene (cakn) expression(1).
AB  - A cDNA, cakn, orthologous to the Arabidopsis KN gene, which is involved in
      vesicle fusion during cell plate formation, was isolated from bell pepper fruit.
      cakn seems to be monogenic and its expression mainly transcriptionally regulated.
      During fruit development, transcript and protein levels increase significantly in
      the early stages in which numerous cell divisions occur, but in the stages
      corresponding to fruit growth by cell enlargement, whereas the messengers are
      undetectable, proteins are still faintly present, suggesting a different
      stability rate for the two types of macromolecules.

PMID- 11311934
TI  - Determination of tRNA(Phe) nucleotides contacting the subunits of Thermus
      thermophilus phenylalanyl-tRNA synthetase by photoaffinity crosslinking.
AB  - The nucleotides of tRNA(Phe) interacting with the subunits of Thermus
      thermophilus phenylalanyl-tRNA synthetase (the alpha(2)beta(2) heterotetramer)
      have been determined by photoaffinity crosslinking of randomly s(4)U
      monosubstituted tRNA(Phe) transcripts which retain aminoacylation parameters
      closely similar to those of the native tRNA(Phe). The thiolated transcripts have
      been fractionated by affinity electrophoresis and separately crosslinked to the
      enzyme. Sites of crosslinking to the beta subunit have been identified at
      positions 33 and 39 and crosslinking sites to the alpha subunit have been
      localized at positions 20, 45 and 47, using alkaline hydrolysis analysis of the
      crosslinked proteinase K-treated tRNAs. An additional crosslink to the beta
      subunit, not identified in the full-length crosslinked tRNAs, has been deduced to
      occur at position 12, based on the analysis of an unusual (fast migrating)
      crosslinked product. Nucleotide s(4)U8 of native tRNA(Phe) has been shown to form
      a minor crosslink to the alpha subunit. Four of the seven crosslinking sites,
      namely nucleotides 8, 12, 20 and 39, are among those shown to be protected
      against cleavage by iodine in footprinting experiments; in contrast, only
      nucleotide 12 is among the contact sites defined in the crystal structure. The
      data of independent biochemical approaches strongly suggest conformational
      flexibility of the complex under functional conditions, thus reflecting the
      importance of macromolecular dynamics for the interaction.

PMID- 11311935
TI  - Cloning and characterization of a human orphan family C G-protein coupled
      receptor GPRC5D.
AB  - Recently three orphan G-protein coupled receptors, RAIG1, GPRC5B and GPRC5C, with
      homology to members of family C (metabotropic glutamate receptor-like) have been
      identified. Using the protein sequences of these receptors as queries we
      identified overlapping expressed sequence tags which were predicted to encode an
      additional subtype. The full length coding regions of mouse mGprc5d and human
      GPRC5D were cloned and shown to contain predicted open reading frames of 300 and
      345 amino acids, respectively. GPRC5D has seven putative transmembrane segments
      and is expressed in the cell membrane. The four human receptor subtypes, which we
      assign to group 5 of family C GPCRs, show 31-42% amino acid sequence identity to
      each other and 20-25% sequence identity to the transmembrane domains of
      metabotropic glutamate receptor subtypes 2 and 3 and other family C members. In
      contrast to the remaining family C members, the group 5 receptors have short
      amino terminal domains of some 30-50 amino acids. GPRC5D was shown to be
      clustered with RAIG1 on chromosome 12p13.3 and like RAIG1 and GPRC5B to consist
      of three exons, the first exon being the largest containing all seven
      transmembrane segments. GPRC5D mRNA is widely expressed in the peripheral system
      but all four receptors show distinct expression patterns. Interestingly, mRNA
      levels of all four group 5 receptors were found in medium to high levels in the
      kidney, pancreas and prostate and in low to medium levels in the colon and the
      small intestine, whereas other organs only express a subset of the genes. In an
      attempt to delineate the signal transduction pathway(s) of the orphan receptors,
      a series of chimeric receptors containing the amino terminal domain of the
      calcium sensing receptor or metabotropic glutamate receptor subtype 1, and the
      seven transmembrane domain of the orphan receptors were constructed and tested in
      binding and functional assays.

PMID- 11311936
TI  - VAM-1: a new member of the MAGUK family binds to human Veli-1 through a conserved
      domain.
AB  - The MAGUKs (membrane-associated guanylate kinase homologues) constitute a family
      of peripheral membrane proteins that function in tumor suppression and receptor
      clustering by forming multiprotein complexes containing distinct sets of
      transmembrane, cytoskeletal, and cytoplasmic signaling proteins. Here, we report
      the characterization of the human vam-1 gene that encodes a novel member of the
      p55 subfamily of MAGUKs. The complete cDNA sequence of VAM-1, tissue distribution
      of its mRNA, genomic structure, chromosomal localization, and Veli-1 binding
      properties are presented. The vam-1 gene is composed of 12 exons and spans
      approx. 115 kb. By fluorescence in situ hybridization the vam-1 gene was
      localized to 7p15-21, a chromosome region frequently disrupted in some human
      cancers. VAM-1 mRNA was abundant in human testis, brain, and kidney with lower
      levels detectable in other tissues. The primary structure of VAM-1, predicted
      from cDNA sequencing, consists of 540 amino acids including a single PDZ domain
      near the N-terminus, a central SH3 domain, and a C-terminal GUK (guanylate kinase
      like) domain. Sequence alignment, heterologous transfection, GST pull-down
      experiments, and blot overlay assays revealed a conserved domain in VAM-1 that
      binds to Veli-1, the human homologue of the LIN-7 adaptor protein in
      Caenorhabditis. LIN-7 is known to play an essential role in the basolateral
      localization of the LET-23 tyrosine kinase receptor, by linking the receptor to
      LIN-2 and LIN-10 proteins. Our results therefore suggest that VAM-1 may function
      by promoting the assembly of a Veli-1 containing protein complex in neuronal as
      well as epithelial cells.

PMID- 11311937
TI  - Characterization of two promoters that regulate alternative transcripts in the
      microtubule-associated protein (MAP) 1A gene.
AB  - We cloned and characterized the mouse gene for microtubule-associated protein
      (MAP) 1A, an important protein for neuronal morphology and mitotic spindle
      formation. We also investigated the 5' untranslated region of the gene to
      characterize the promoter units. Two alternative transcripts different in the 5'
      region were identified by 5' RACE. Both transcripts were principally observed in
      the brain. Genomic cloning revealed that exons 1, 2, and 4 generate the 5' part
      of a long transcript, whereas exons 3 and 4 generate a short transcript. Putative
      5' and intronic promoters flanking exons 1 and 3, respectively, are GC-rich and
      lack a canonical TATA box. DNase I footprinting from mouse cells revealed that
      several potential cis-elements were occupied by nuclear proteins. A reporter
      assay system in conjunction with a number of deletion and mutation constructs was
      used to test the two putative promoters. Both putative promoters showed
      transactivity and their function was dependent upon Sp1 sites. In addition, an NF
      1 site, an HNF3B site, and an AP-1/ATF site were necessary for basal promoter
      activity of the intronic promoter. Our data provide insight into the regulatory
      mechanisms that govern the expression of the MAP1A gene.

PMID- 11311938
TI  - Molecular cloning of the rat TA1/LAT-1/CD98 light chain gene promoter.
AB  - The rat LAT-1 (L-amino acid transporter-1) gene is a CD98 light chain highly
      expressed in cancer and development. As an initial study of the molecular basis
      underlying regulation of its expression, we cloned 2 kb of the LAT-1 5' flanking
      region. Inverse RACE and primer extension methods were used to define the
      transcription initiation site at 80 bp upstream from the translational start
      site. Functional studies carried out in normal hepatic cells using constructs
      containing progressive 5' deletion from region -1958 to -185 showed 3-5-fold beta
      galactosidase activities over control. The presence of an activator site(s)
      between -52 and -185 was indicated by low activities conferred by the construct
      spanning this region.

PMID- 11311939
TI  - Promoter of the gene encoding the 16 kDa DNA-binding and apoptosis-inducing C1D
      protein.
AB  - The 5' region of the gene encoding the human 16 kDa DNA-binding and apoptosis
      inducing C1D protein was analysed for promoter activity. Sections of this region
      were cloned into a promoterless vector containing the enhanced green fluorescent
      protein (EGFP) as reporter gene. Expressed EGFP was estimated in transfected
      cells by quantitative fluorescence microscopy. The sequence between mRNA
      positions ATG -868 and ATG -12 results in relatively highest EGFP expression in
      transiently transfected human and murine cells. The upstream segment immediately
      adjacent to the 5' end of the most active fragment was identified as an inverted
      LINE-1 repeat element. Transient transfection experiments point to the presence
      of cis-acting repressing sequences on this LINE-1 element which reduce the
      transcriptional activity of the basal C1D promoter in human and murine cells by
      more than 95%. This result supports previous evidence suggesting that LINE-1
      sequences may function as regulatory elements to control the expression of nearby
      genes.

PMID- 11311941
TI  - Cloning and expression analysis of a cDNA that encodes a leech hemerythrin.
AB  - We report the cDNA sequence of a leech hemerythrin. A cDNA was isolated from a
      Theromyzon tessulatum cDNA library and encodes a 120 amino acid protein of about
      14 kDa. The predicted protein contains the hemerythrin signature sequence and the
      iron ligand residues previously identified in crystal structures of hemerythrin
      and myohemerythrin. The protein displayed the highest identity to myohemerythrin,
      a non-heme iron-binding protein described in sipunculids. Expression analysis
      indicated that the mRNA is widely expressed in leech and is stage specific in
      appearance, being absent after the two first blood meals, appearing after the
      last blood meal during the period preceding oogenesis and disappearing after egg
      laying.

PMID- 11311940
TI  - Promoter analysis of the Drosophila melanogaster gene encoding transcription
      elongation factor TFIIS.
AB  - The promoter region of the Drosophila melanogaster TFIIS gene was characterized
      by transient expression assay. Serial deletion analysis of the promoter region
      showed that the promoter region between -112 and +113 is required for the
      efficient expression of the D. melanogaster TFIIS gene. The results also suggest
      that the DNA fragments between -112 and -54 and between +94 and +113 contain the
      vital elements for the expression. The importance of these fragments was further
      substantiated by the findings that the sequences in these fragments of the D.
      melanogaster TFIIS gene are conserved in the 5'-flanking regions of the
      Drosophila virilis TFIIS gene. The comparison of the nucleotide sequences in the
      5'-flanking region of the D. melanogaster and D. virilis TFIIS genes revealed
      that the three regions, -85--59, +76-+126, and the vicinity of the transcription
      initiation site of the D. melanogaster TFIIS gene, are conserved. It is very
      interesting that the long downstream DNA between +76 and +126 is highly conserved
      with 90% identities between the two species. The downstream promoter region
      between +94 and +113 of the D. melanogaster TFIIS gene was further analyzed by
      transient expression and band mobility shift assays. The results obtained suggest
      that the region between +94 and +113 is probably recognized by nuclear factors
      and that the sequence (+98)AGTAAACAACAT(+109) seems to make a great contribution
      to promoter activity of the D. melanogaster TFIIS gene.

PMID- 11311943
TI  - The genomic structure of SYCP3, a meiosis-specific gene encoding a protein of the
      chromosome core.
AB  - SYCP3 localizes to the lateral elements of the synaptonemal complex and is
      essential for male meiosis. The genomic structure of SYCP3 consists of nine exons
      spanning approximately 14 kb. In mouse and rat, but not in hamster, the putative
      translation start of SYCP3 is present in the first exon. The putative promoter of
      SYCP3 was also cloned and shown to drive transcription of a reporter gene in
      somatic cells.

PMID- 11311942
TI  - Isolation and characterization of a cDNA encoding a novel member of the human
      regenerating protein family: Reg IV.
AB  - Human Reg and Reg-related genes constitute a multi-gene family belonging to the
      calcium (C-type) dependent lectin superfamily. Regenerating gene family members
      are expressed in the proximal gastrointestinal (GI) tract and ectopically at
      other sites in the setting of tissue injury. By high-throughput sequence analysis
      of a large inflammatory bowel disease library, two cDNAs have been isolated which
      encode a novel member of this multigene family. Based on primary sequence
      homology, tissue expression profiles, and shared exon-intron junction genomic
      organization, we assign this gene to the regenerating gene family. Specific
      protein structural differences suggest that the current three regenerating gene
      subtypes should be expanded to four. We demonstrate that Reg IV has a highly
      restricted tissue expression pattern, with prominent expression in the
      gastrointestinal tract. Reg IV mRNA expression is significantly up-regulated by
      mucosal injury from active Crohn's disease or ulcerative colitis.

PMID- 11311944
TI  - ZNF232: structure and expression analysis of a novel human C(2)H(2) zinc finger
      gene, member of the SCAN/LeR domain subfamily.
AB  - We have identified a novel zinc finger gene, ZNF232, mapped to human chromosome
      17p12. The coding region of the gene is organized in three exons corresponding to
      a 417 amino acid long polypeptide containing a SCAN/LeR domain and five C(2)H(2)
      type zinc fingers. ZNF232 is possibly a nuclear protein, as suggested by
      expression analysis of GFP/ZNF232 chimeric constructs. ZNF232 transcripts were
      detected in a wide collection of adult human tissues. The gene is possibly
      subjected to tissue-specific post-transcriptional regulation by means of
      alternative splicing.

PMID- 11311945
TI  - Cloning and characterization of a novel Kruppel-like zinc finger gene, ZNF268,
      expressed in early human embryo.
AB  - With the aim of identifying genes involved in early human embryonic development,
      we have isolated a cDNA clone representing a novel human zinc finger gene ZNF268
      from 3 week old human embryo cDNA library using a differential hybridization
      strategy. The complete cDNA sequence of ZNF268 contained an open reading frame of
      2841 nucleotides that encodes a 947 amino acid protein with an N-terminal Kruppel
      associated box (KRAB) domain and 24 C-terminal zinc fingers. Northern blot
      analysis showed that ZNF268 mRNA is mainly expressed in 3-5 week old human
      embryos suggesting it could play certain roles in the embryogenesis. The gene
      consists of six exons spanning about 22 kb of genomic DNA. According to the
      genomic sequence from the HTGS database, the ZNF268 gene is assigned to human
      chromosome 5.

PMID- 11311946
TI  - cDNA sequence of human carbonic anhydrase-related protein, CA-RP X: mRNA
      expressions of CA-RP X and XI in human brain.
AB  - A full-length cDNA clone of human carbonic anhydrase-related protein (CA-RP) X
      was obtained and sequenced. The 2720 bp long cDNA sequence was predicted to
      encode a 328 amino acid polypeptide. The deduced amino acid sequence showed an
      overall similarity of 25-57% to other CA isozymes and the highest % similarity to
      a CA-RP XI. Similar to CA-RP XI, CA-RP X lacked two out of three zinc-liganded
      histidine residues, suggesting no biological activity of CA. Northern blot
      analysis demonstrated an approx. 2.8 kb transcript in the human brain and kidney.
      RNA dot blotting showed significant signals for CA-RP X and XI mRNA expressions
      in the adult total brain and almost all parts of the central nervous system, but
      no expression in the fetal brain. These results suggest that CA-RP X and XI play
      some role in human brain, especially in brain development.

PMID- 11311947
TI  - Isolation and characterisation of a cassava catalase expressed during post
      harvest physiological deterioration.
AB  - Storage roots of cassava undergo a rapid, endogenous, post-harvest deterioration
      response that is thought to involve oxidative processes. A cassava catalase
      (MecCAT1) was isolated from a root cDNA library. The transcript is expressed
      predominantly in roots with little expression in leaves. Catalase enzyme activity
      and MecCAT1 transcript expression during the post-harvest period were compared in
      highly susceptible and less susceptible cultivars and suggest that high levels of
      catalase activity may play a role in delaying the deterioration response.

PMID- 11311948
TI  - Molecular characterization of cDNA clones for ADP-glucose pyrophosphorylase from
      Citrus.
AB  - Two cDNA clones encoding ADP-glucose pyrophosphorylases have been isolated from
      fruit and leaf cDNA libraries of Citrus (Citrus unshiu Mac. cv. Miyagawa) in
      which one was designated as agpS for the small subunit and the other as agpL for
      the large subunit. Both cDNAs have uninterrupted open reading frames deriving 57
      58 kDa polypeptides. The deduced amino acid sequence of agpS has a unique
      feature. That is, it lacks a cysteine residue (Cys-12) which is usually conserved
      in all other dicot enzymes. This is the first report of agpS lacking Cys-12 among
      dicot small subunits. The expression pattern of both subunits showed a different
      profile in which leaves synthesized both agpS and agpL more vigorously than those
      of fruits. During leaf development, the transcripts of agpS and agpL showed a
      higher expression level at younger stages. During fruit development, the
      expression level of both subunits was observed to be highest in the mini-green
      stage, but it decreased in the small green stage and it increased again towards
      the maturing stage. These results suggest that both subunits may play an
      important role in the regulation of Citrus fruit and leaf development.

PMID- 11311949
TI  - VDAC2 (porin-2) expression pattern and localization in the bovine testis.
AB  - In this study, sequencing of voltage-dependent anion channel 2 (VDAC2, porin-2)
      cDNA from bovine testis is reported. High identity to the murine, rabbit, and
      human subtypes at both the nucleotide and amino acid levels is demonstrated. mRNA
      analysis revealed expression of VDAC2 in bovine testis, whereas high levels of
      VDAC2 proteins were found in late spermatocytes, spermatids, and spermatozoa. In
      contrast, VDAC1 (porin-1) is exclusively localized in Sertoli cells. The possible
      role of testicular VDAC2 in providing energy metabolites and in germ cell
      apoptosis is discussed.

PMID- 11311950
TI  - Sense and sensitivity--designing surveys based on an imperfect test.
AB  - Designing a survey to detect the presence of a disease is complicated if the test
      used to detect the disease has non-perfect sensitivity and specificity. This
      paper gives two new approximations that simplify such a task. The first gives the
      cumulative probability distribution of the number of apparently diseased animals
      detected in the survey and the second gives the probability that no diseased
      animals are detected if the test used has 100% specificity. Both approximations
      can be used to determine confidence limits for the true prevalence. The main
      purpose of the approximations is to determine the number of animals that need to
      be tested to be confident that a herd is free of disease, and then to determine
      the number of herds that need to be tested to demonstrate area freedom. One
      approach to such an area survey has been to classify each herd as diseased or not
      based on the number of reactors found in the herd, and then to use the number of
      herds classified as diseased to determine the area's status. The paper points out
      that basing the decision simply on the magnitude of the maximum observed within
      herd reactor proportion results in a more accurate survey for the same number of
      animals and herds tested.

PMID- 11311951
TI  - Host factors associated with the detection of Aeromonas salmonicida and Yersinia
      ruckeri in Ontario, Canada government fish hatcheries.
AB  - This paper presents an epidemiological investigation of Ontario Ministry of
      Natural Resources Fish Health Laboratory data from 1981 to 1997, to determine
      whether fish species and age were associated with lot-level detection of
      Aeromonas salmonicida and Yersinia ruckeri in hatchery fish. In stepwise logistic
      regression, the species brook trout and back-cross (lake trout crossed with the
      hybrid "splake") were more likely to test A. salmonicida-positive compared to all
      other species reared in the hatcheries. Similarly, the species brook trout was
      significantly more likely to test Y. ruckeri-positive compared to all other
      species. For both pathogens, the 1-5-month age group was associated significantly
      with detection. These findings suggest that purposive sampling of higher-risk
      fish lots could increase the likelihood of detecting both study pathogens.

PMID- 11311952
TI  - Estimation of animal-level prevalence from pooled samples in animal production.
AB  - Often, the prevalence of an infection in the animal-production sector is
      determined at the group level. The prevalence at animal level (p) gives more
      precise information on the infection status of the sector. This paper shows that
      pooled-sample data together with mathematical models allow for estimation of p.
      For this, model assumptions have to be made on the variation of p between groups
      separated in space and/or time. Formulas were derived for four models that were
      based on different assumptions. Model 1 assumed that p has the same value for all
      groups. Models 2-4 assumed that some of the groups were not infected. In
      addition, model 2 assumed that p has the same value for all infected groups;
      model 3 assumed that for an infected group, p is equal to either p(1) or p(2);
      and model 4 assumed that p was Beta distributed among infected groups. The models
      were applied to data sets on Salmonella infection in broiler flocks, including
      serotype data dominated by S. Hadar and S. Paratyphi B, var. Java. Based on
      likelihood-ratio tests, models 3 and 4 consistently fitted significantly better
      to the data. The applicability of model 4 is numerically bounded, related to the
      shape of the Beta distribution of p. Model calculations show that flock-level
      prevalence of Salmonella is much higher after than before slaughter. This
      difference (which possibly is related to different types of samples) is much
      smaller at the animal level. An important result of the estimation of p is that
      it in turn allows for an estimation of the proportion of false-negative groups-
      which is important in estimating the effect of veterinary or public-health
      measures.

PMID- 11311953
TI  - Cross-sectional study of the seroprevalence to Borrelia burgdorferi sensu lato
      and granulocytic Ehrlichia spp. and demographic, clinical and tick-exposure
      factors in Swedish horses.
AB  - A cross-sectional study of the seroprevalence to Borrelia burgdorferi sensu lato
      and granulocytic Ehrlichia spp. in Swedish horses was conducted to evaluate
      associations with demographic, clinical and tick-exposure factors. From September
      1997-1998, blood samples from 2018 horses were collected from the animals
      presented to veterinary clinics affiliated with the Swedish Horserace Totalizator
      Board (regardless of the primary cause for consultation). Standardized
      questionnaires with information both from owners and attending veterinarians
      accompanied each blood sample. The apparent seroprevalences to B. burgdorferi s.
      l. and granulocytic Ehrlichia spp. were 16.8 and 16.7%, respectively. The
      northern region had the lowest seroprevalences. Four logistic models were
      developed (controlling for demographic variables). In the disease model of
      seropositivity to B. burgdorferi s. l., age, breed, geographic region, the
      serologic titer to granulocytic Ehrlichia spp., season and the diagnosis coffin
      joint arthritis were significant. In the tick-exposure model of B. burgdorferi s.
      l., pasture access the previous year and gender were significant. Age, racing
      activity, geographic region, season and the serologic titer to B. burgdorferi s.
      l. were associated with positivity to granulocytic Ehrlichia spp. In the tick
      exposure model of granulocytic Ehrlichia spp., pasture access was a risk factor.
      An interaction between racing activity and geographic region showed that the risk
      of positive serologic reactions to Ehrlichia spp. was increased in the horse
      population in the south and middle of Sweden, but only among horses not used for
      racing. Except for the positive association between coffin-joint arthritis and
      serologic reactions to B. burgdorferi s. l., there were no significant
      associations in the multivariable models between non-specific or specific
      clinical sign or disease with seropositivity to either of these agents.

PMID- 11311954
TI  - A multicenter, matched case-control study of risk factors for equine laminitis.
AB  - Risk factors for equine laminitis were examined in a prospective case-control
      study of the 258 cases seen at six collaborating veterinary teaching hospitals
      over a 32-month period. Case-control pairs were matched on institution,
      clinician, and season of diagnosis. The 90% of case-control pairs (78 acute, 155
      chronic) that had complete data for age, gender, and breed were used in separate
      conditional logistic-regression models for acute and chronic laminitis. There was
      an increase in risk for horses with acute laminitis from 5 to 7 years of age (OR
      4.7, 95% CI 1.3-16) and from 13 to 31 years of age (OR 3.9, 95% CI 1.3-12) (both
      compared to <5 years); risk was increased for chronic laminitis from 10 to 14
      years (OR 3, 95% CI 1.4-6.8) and from 15 to 38 years (OR 2.9, 95% CI 1.4-6.1)
      (both compared to <6 years). Mares - but not stallions - were more likely than
      geldings to develop acute laminitis (OR 2.6, 95% CI 1.1-6.2) and chronic
      laminitis (OR 2.0, 95% CI 1.1-3.6). In the small acute-laminitis data set, the
      breed variable was collapsed into three categories: Thoroughbred (THB,
      reference), the Quarter Horse (QH), and other (non-QH-THB). The non-QH-THB group
      was at increased risk of acute laminitis (OR 3.8, 95% CI 1.2-11.8). For the seven
      breed-group categories used in the chronic-laminitis model, however, all non-THB
      breed groups appeared significantly at risk as compared to the THB, with odds
      ratios ranging from 3.3 (95% CI 1.3-8.30) for the QH to 9.1 (95% CI 2.1-39.3) for
      ponies.

PMID- 11311955
TI  - Censoring in survival analysis: a simulation study of the effect of milk yield on
      conception.
AB  - Survival-analysis methods often are used to analyze data from dairy herds where
      the outcome of interest is the interval from calving to conception. The purpose
      of this study was to determine whether an association between milk yield and
      culling biases the estimation of the effect of milk yield on conception. This was
      done by simulating four different scenarios modeling dairy-cattle milk yield and
      reproductive performance with known relationships among study factors. Cox's
      proportional-hazards model was used to analyze the effect of milk yield on days
      open under the following four scenarios: (1) no association between milk yield
      and culling or between milk yield and conception; (2) association between milk
      yield and culling only; (3) association between milk yield and conception only;
      (4) associations between milk yield and both culling and conception. The analyses
      also were repeated for data sets with an association between milk yield and
      culling, but with probabilities of culling ranging from 0.01 to 0.4. An effect of
      milk production on culling appeared to cause a small increase in the parameter
      estimates for the association of milk yield and days open - particularly when the
      probability of culling was high. The effect of high milk production on median
      days open (as estimated by survival functions) changed by 2 to 4 days when an
      association between milk yield and culling was programmed in the simulated data
      sets.

PMID- 11311956
TI  - A field trial of the effect of improved piglet management on smallholder sow
      productivity in the Philippines.
AB  - We conducted a randomised, controlled field trial during 1998/1999 to evaluate
      the hypothesis that improved piglet management would improve the reproductive
      performance of smallholder sows. Simple changes were introduced into the
      treatment herds including the construction of a heated piglet-separation pen,
      vitamin injections, creep feeding and early weaning. The control herds were
      unchanged. Data were collected from all sows in each enrolled herd over two
      farrowings. We enrolled 176 sows, including 170 (96 treatment and 74 control)
      sows that remained throughout the study period. Significant differences in the
      reproductive performance of treatment and control sows were recorded for
      interfarrowing interval (median 176 versus 220 days), average number liveborn
      over 2 litters (11 versus 12), and average preweaning mortality over 2 litters (0
      versus 37%). Based on a discount rate of 17%, the benefit-cost ratio of the
      treatment was 11.1 and 12.1 over 3 and 5 years, respectively.

PMID- 11311957
TI  - Antibody-ELISA seroprevalence of bovine trypanosomosis in the Eastern Province of
      Zambia.
AB  - A longitudinal study was conducted over a 1-year period in six selected villages
      in Petauke and Katete districts in the Eastern Province of Zambia. Starting in
      November 1997, 50 animals were sampled at random at each village every 2 months.
      The parasitological prevalence of trypanosomosis was determined by the
      haematocrit centrifugation buffy-coat technique, supplemented with thick and thin
      Giemsa-stained blood films. Serum samples also were collected for anti
      trypanosomal antibody determination by indirect enzyme-linked immunosorbent
      assay. Parasitological prevalence was highly variable between villages and
      between visits (range: 0-28.6%; median: 3.1%). Seroprevalence was also variable
      between villages (range: 0-80.8%; median: 50%), but was less variable between
      visits. Average annual parasitological prevalence and average annual
      seroprevalence for each village were highly correlated
      [R(2)(adjustedford.f.)=0.89, p<0.01]. Seroprevalence measured on any single visit
      to a study village was better than parasitological prevalence as a predictor of
      average annual parasitological prevalence.

PMID- 11311958
TI  - Risk factors for clinical salmonellosis in Virginia, USA cattle herds.
AB  - Veterinarians working in several Virginia, USA counties noticed an increase in
      clinical salmonellosis in cattle herds during 1994. We conducted a case-control
      study to identify potential risk factors for salmonellosis in cattle herds in
      this region. The potential impact of exposure to poultry-related factors was of
      particular interest because of the close proximity of poultry and cattle
      operations in this part of the state. Information was collected from 23 case
      farms and 23 control farms matched by herd veterinarian, type of enterprise (beef
      vs. dairy), and location. Faecal and environmental samples were collected during
      herd visits for bacteriologic culture. Salmonella was isolated from 4.7% of 531
      faecal, feed, water, and environmental samples collected. Salmonella Typhimurium
      was the serotype found most frequently in clinical cases in participating herds
      and from samples collected during study visits. Case herds had a higher
      percentage of study samples positive for Salmonella. Potential risk factors were
      screened using methods for pair-matched data and then analyzed in individual
      conditional logistic-regression models to estimate odds ratios with 95% profile
      likelihood confidence intervals. Significant factors included: the number of
      mature cows in the herd (OR=1.01; CI 1.00, 1.03), percent change in the number of
      mature cows during 1994 (OR=0.68; CI 0.11, 0.96), having calves usually born in a
      building rather than outdoors (OR=0.17; CI 0.01, 0.98), poultry manure spread on
      bordering property (OR=4.00; CI 1.00, 26.50), signs of rodents in cattle-housing
      or feed-storage areas (OR=2.75; CI 0.94, 9.92), and contact of wild geese with
      cattle or feed (OR=4.5; 1.16, 29.51).

PMID- 11311961
TI  - Beneficial effect of supplementation with copper sulfate on STZ-diabetic mice
      (IDDM).
AB  - Trace element status is known to be altered in the diabetic state. Current
      evidence suggests that reactive oxygen intermediates (ROI's) do participate in
      the destruction of pancreatic beta cells in STZ-induced Type 1 diabetes. The
      copper and zinc status of diabetic patients and their descendants was also found
      to have changed. The aim of this study was to evaluate the potential usefulness
      of copper sulfate in the treatment of STZ-induced type I diabetes. We used C57BL6
      female mice, in whom copper sulfate treatment was started at 6 weeks of age
      followed by an IP injection of 40 mg/kg body weight of STZ for five consecutive
      days. Its effects were evaluated at 10 weeks of age. The treatment with copper
      sulfate significantly decreased blood glucose levels, levels of lipid
      peroxidation and mRNA expression of the enzyme iNOS and the cytokines IFN-gamma
      and IL-4. Histological analysis of the pancreas revealed that, three out of five
      animals in the copper sulfate treated groups showed absence of mononuclear cell
      infiltration and no change in the shape and size of islets as compared to
      pancreas of the STZ-induced diabetic group of animals. In conclusion, our
      observations indicate that copper sulfate treatment can exert beneficial effects
      in diabetes with preservation of beta-cell function in vivo. Copper sulfate could
      be exerting these beneficial effects either by acting directly by reducing free
      radicals or through reduction in glucose levels.

PMID- 11311962
TI  - Enhancement of glomerular heme oxygenase-1 expression in diabetic rats.
AB  - An increase in oxidative stress in diabetic subjects is implicated to play a
      pivotal role in diabetic vascular complications. In response to oxidative stress,
      antioxidant enzymes are considered to be induced and protect cellular functions
      to keep in vivo homeostasis. However, it remains to be clarified whether
      antioxidant enzymes are induced against oxidative stress especially in renal
      glomeruli at an early stage of diabetes. To answer this question, we examined the
      gene expression of a variety of antioxidant enzymes in glomeruli isolated from
      streptozotocin-induced diabetic rats. The mRNA expression of antioxidant enzymes
      such as catalase, glutathione peroxidase, and CuZn-superoxide dismutase, was
      unaltered in glomeruli of diabetic rats and was comparable to control rats. In
      contrast, the mRNA expression of heme oxygenase-1 (HO-1) was enhanced in
      glomeruli of diabetic rats as compared with control rats. A treatment with
      insulin as well as with vitamin E (40 mg/kg body weight every other day, intra
      peritoneal injection) normalized the mRNA expression of HO-1 in the glomeruli of
      diabetic rats. Immunohistochemical analysis revealed that the up-regulated
      expression of HO-1 protein was localized in glomerular cells of diabetic rats. In
      conclusion, these results provide the first evidence that among antioxidant
      enzymes HO-1 expression is preferentially increased in diabetic glomeruli.

PMID- 11311963
TI  - Peripheral blood mitochondrial DNA content is inversely correlated with insulin
      secretion during hyperglycemic clamp studies in healthy young men.
AB  - Abnormalities in mitochondrial DNA(mtDNA) have been implicated in the
      pathogenesis of diabetes mellitus. We recently reported that decreased mtDNA
      content precedes the development of diabetes mellitus and is associated with
      parameters of insulin resistance. In this study, we examined whether there is any
      relation between mtDNA content and insulin secretion. We compared the mtDNA
      content of peripheral blood leukocytes with the parameters of insulin secretion
      measured by hyperglycemic clamp in a group of healthy young men. There were
      statistically significant correlations between mtDNA content in peripheral blood
      and fasting plasma insulin (r=-0.43, P<0.05) and C-peptide levels (r=-0.44,
      P<0.05). MtDNA content also correlated negatively with acute insulin response(r=
      0.48, P<0.05), late insulin response (r=-0.50, P<0.05) during hyperglycemic clamp
      and insulin secretion after glucagon stimulation (r=-0.60, P<0.01). mtDNA content
      in peripheral blood correlated negatively with homeostasis model (HOMA) insulin
      resistance (r=-0.45, P<0.05) although it did not correlate with the insulin
      insensitivity index (M/I) during hyperglycemic clamp. In summary, the mtDNA
      content of peripheral blood correlated negatively with indices of insulin
      resistance and insulin secretion in healthy young men. The compensatory response
      of pancreas beta cells to insulin resistance might contribute in part to
      increased insulin secretion in these subjects.

PMID- 11311964
TI  - Characteristics of pancreatic beta-cell secretion in Type 2 diabetic patients
      treated with gliclazide and glibenclamide.
AB  - The aim of the present cross-over study was to compare the beta-cell response to
      gliclazide and glibenclamide administered orally during and following a
      hyperglycaemic clamp in sulphonylurea treated Type 2 diabetes. Nine patients (6
      males), aged 61.4 (S.D. 6.9) years with a body mass index of 27.5 (3.1) kg m(-2)
      and HbA(1c) at baseline of 7.2 (0.9)% were included. Eight healthy control
      subjects underwent the same tests. Patients received 80-240 mg gliclazide or 5-15
      mg glibenclamide for 6 weeks. Thirty minutes after administration of 160 mg of
      gliclazide or 10 mg of glibenclamide a 1-h hyperglycaemic clamp (11.0 mmol l(-1))
      was begun, and followed by a 3.5-h observation period. Nadir blood glucose levels
      were 4.2 (1.0), 4.3 (1.2) and 3.4 (1.0) mmol l(-1) for glibenclamide gliclazide
      and controls, respectively (both P=0.07 vs. controls). Glucose levels decreased
      slowly and linearly in people with diabetes and reached nadirs after 204 (8) and
      198 (18) min, respectively, after cessation of glucose infusion, while in
      controls, glucose levels declined steeply to a nadir at 98 (47) min (P<0.003 vs.
      both drugs). No first phase insulin secretion peak was observed in people with
      diabetes. Insulin levels remained elevated during the 3-h observation period in
      SU treated patients but, in control subjects decreased to baseline values within
      2 h of the clamp. The proinsulin to C-peptide ratio increased during the
      observation period. In conclusion, the effects of glibenclamide and gliclazide on
      insulin secretion are very similar in patients with Type 2 diabetes who are in
      moderate glycaemic control, with a slow rise to lower amplitude, poor
      responsiveness to falling glucose levels, and raised proinsulin to C-peptide
      ratio.

PMID- 11311965
TI  - Diabetic complications are associated with liver enzyme activities in people with
      type 1 diabetes.
AB  - This study was performed to clarify if diabetic complications are associated with
      liver enzyme activities in type 1 diabetic outpatients. Elevated activities of
      serum aminotransferases are a common sign of liver disease and are observed more
      frequently among people with diabetes than in the general population. Many
      studies have shown an association between specific diabetic complications and
      disturbances in various tissues, such as diabetic nephropathy and cardiovascular
      diseases, but only limited data are available on the possible association between
      diabetic complications and liver function. We studied 28 patients with type 1
      diabetes. Mean age was 43.4+/-9.5 (S.D.), and duration of diabetes 25.2+/-9.7.
      Limited joint mobility (LJM) was assessed by the Rosenbloom's method. Background
      and proliferative retinopathy, and peripheral symmetrical polyneuropathy were
      also assessed. Activities of alanine amino transferase (ALT), gamma-glutamyl
      transferase (GGT) and alkaline phosphatase (ALP) in serum were determined. The
      metabolic control of the diabetes was evaluated by the glycosylated haemoglobin
      A(1c) (HbA(1c)) level and lipid values were also measured. ALT activity was
      associated with LJM (P<0.01) and with neuropathy (P<0.01). Association between
      GGT activity and LJM (P<0.01) and neuropathy (P<0.01) were also found. GGT
      activity was also associated with the severity of retinopathy (P<0.01). None of
      these associations was explained by confounding effects of diabetes duration,
      age, body mass index (BMI), HbA(1c) or alcohol consumption. In conclusion,
      diabetic complications such as LJM, retinopathy and neuropathy are associated
      with liver enzyme activities independent of alcohol consumption, BMI and
      metabolic control of diabetes.

PMID- 11311966
TI  - Relationship between serum tumor necrosis factor-alpha and insulin resistance in
      obese men with Type 2 diabetes mellitus.
AB  - We analyzed serum concentrations of tumor necrosis factor-alpha (TNF-alpha) for
      their role in insulin resistance in 12 obese men with untreated Type 2 diabetes
      mellitus and in 6 age-and BMI-matched obese controls. Insulin resistance was
      expressed using the homeostasis model assessment (HOMA-R). Six of the patients
      were insulin-resistant (HOMA-R>5.0), while six were not (HOMA-R</=3.0). Serum
      levels of TNF-alpha were higher in patients with insulin resistance (4.19+/-0.96
      pg/ml) than in patients without insulin resistance (2.52+/-1.64 pg/ml) and in
      controls (2.03+/-1.21 pg/ml). Fasting serum concentrations of insulin and HOMA-R
      were higher in patients with insulin resistance (16.2+/-5.0 and 6.30+/-1.0 IU/ml,
      respectively) than in patients without insulin resistance (7.3+/-2.2 and 2.4+/
      0.6 IU/ml) and in controls (8.0+/-2.9 and 1.8+/-0.6 IU/ml). These data suggest
      that high levels of serum TNF-alpha in patients with insulin resistance are
      related to high levels of fasting insulin and HOMA-R. We conclude that TNF-alpha
      may be involved in the pathogenesis of Type 2 diabetes mellitus in obese men. The
      importance of this investigation is that the subjects recruited in the study are
      BMI matched, because human obesity is associated with an increased TNF-alpha mRNA
      expression in adipose tissue.

PMID- 11311967
TI  - Age at diagnosis, glycaemic control and the development of retinopathy in a
      population-based cohort of Type 1 diabetic subjects in Canterbury, New Zealand.
AB  - The aim was to determine the relationship between age at diagnosis, glycaemic
      control and the development of retinopathy in a population-based cohort of Type 1
      diabetic subjects. At 1 January 1984, there were 286 individuals with Type 1
      diabetes (and age of onset<20 years) on the Canterbury, New Zealand population
      register who had at least 2 prospective HbA(1c) readings (from 1 January 1984).
      Of these, 107 already had retinopathy. Of the 179 subjects without retinopathy at
      baseline 63 developed retinopathy during follow-up. After controlling for
      duration of diabetes (in the whole group), age at diagnosis was found to be a
      significant predictor of HbA(1c) level (P=0.001), with higher (mean+/-SD)
      baseline HbA(1c) in the 10-14 age group (7.95+/-2.14%), compared with (7.62+/
      1.77%) in the <10 year group and (7.39+/-2.57%) in the >14 year group. The major
      predictors of retinopathy (in those without retinopathy at baseline), however
      were duration of diabetes (mean time to development of retinopathy decreases by
      14% (95% CI 10-17%) for each year), baseline HbA(1c) (for each unit increase,
      mean time to development of retinopathy decreased by 23% (95%CI 13-32%) and
      HbA(1c) slope (average annual change). Peri-pubertal age at diagnosis (10-14
      years) did not influence the time to onset of retinopathy over and above that
      attributed to duration of diabetes and glycaemic control.

PMID- 11311968
TI  - Determinants of albuminuria in people with Type 2 diabetes mellitus.
AB  - This study sought to identify determinants of albuminuria in people with Type 2
      diabetes. In 335 primary care patients, we assessed albumin-creatinine ratio
      (ACR) in two 24-h urine samples, and its cross-sectional associations with
      protein and alcohol intake, cigarette smoking, body weight and height,
      glycosuria, blood pressure, hypoglycaemic and antihypertensive treatment, gender,
      age, age at diagnosis, diabetes duration, family history of diabetes and
      cardiovascular diseases, ethnic origin, and education. The prevalence of micro-
      or macro-albuminuria (ACR> or =2.0 mg/mmol) was 33%. Among these patients,
      compared to those with normo-albuminuria, there were more men, protein intake
      (g/kg) estimated from urinary urea as well as systolic blood pressure and
      glycosuria were higher, there were more smokers, men were shorter, and a family
      history of diabetes was less prevalent (all P<0.05). In linear and logistic
      regression (n=270) albuminuria was independently associated (P<0.05 unless
      indicated otherwise) with systolic blood pressure (OR(10 mmHg)=1.32), smoking
      (OR(ex/never)=2.36, OR(current/never)=4.89), glycosuria (OR(> or =7/<1
      g/l)=2.41), gender (OR(men/women)=2.50), age in men (OR(10 year)=1.60) (P<0.10)
      and, inversely, in women (OR(10 year)=0.63) (P>0.10). On aggregation, the
      modifiable determinants systolic blood pressure, smoking and glycosuria explained
      12% of the variation in albuminuria. These factors thus are, although to a
      moderate extent only, potential determinants of albuminuria. We also observed an
      independent, inverse association with body height (OR(0.10 m)=0.47). This is in
      line with the hypothesis that development in utero or during early life
      influences kidney function in later life.

PMID- 11311969
TI  - Microalbuminuria is associated with the insulin resistance syndrome independent
      of hypertension and type 2 diabetes in the Korean population.
AB  - To investigate whether microalbuminuria is associated with the insulin resistance
      syndrome independent of hypertension and type 2 diabetes, we studied the
      association between microalbuminuria and features of insulin resistance syndrome
      in Korean general population. We selected 1006 subjects by a random cluster
      sampling among residents aged >40 years living in the Chung-Up district, a rural
      area of South Korea. Subjects were stratified by oral glucose tolerance status
      [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes
      mellitus], and by the presence or absence of hypertension. Urinary albumin
      excretion rate (UAER) was determined using timed overnight urine collection.
      Various cardiovascular risk factors including anthropometric indices, serum
      lipid, true insulin and proinsulin concentrations were also measured. The
      prevalence of microalbuminuria (UAER between 20 and 200 microg/min) increased as
      the glucose tolerance worsened (6.0% in NGT, 11.8% in IGT, and 21.8% in diabetes;
      chi(2) trend=25.9, P<0.001). Subjects with microalbuminuria had a higher body
      mass index (BMI), waist-to-hip circumference ratio (WHR), systolic and diastolic
      blood pressure (BP), fasting and 2 h plasma glucose, fasting plasma insulin and
      proinsulin levels, and lower HDL-cholesterol level than subjects without
      microalbuminuria. In multiple regression analysis, BMI, diastolic BP, 2 h plasma
      glucose, and fasting plasma insulin levels were found to be independent factors
      associated with UAER. Multiple logistic regression analysis showed that not only
      diabetes mellitus and hypertension, but also fasting hyperinsulinemia and waist
      to-hip ratio were independent factors associated with the presence of
      microalbuminuria. When the normotensive, non-diabetic subjects were analyzed
      separately, fasting hyperinsulinemia and impaired glucose tolerance remained
      independent variables associated with the presence of microalbuminuria. These
      results show that microalbuminuria in the Korean general population is associated
      with hyperinsulinemia and central obesity, and suggest that microalbuminuria is a
      feature of the insulin resistance syndrome independent of hypertension or type 2
      diabetes.

PMID- 11311970
TI  - Forskolin inhibits expression of inducible nitric oxide synthase mRNA via
      inhibiting the mitogen activated protein kinase in C6 cells.
AB  - This study has demonstrated the mechanism of protein kinase A (PKA)-dependent
      inhibition of astrocytic nitric oxide production and inducible NO synthase mRNA
      expression induced by lipopolysaccharide. In C6 glioma cells, the stimulation
      with lipopolysaccharide (LPS; 1 microg/ml) evoked increases of nitric oxide (NO)
      production, NO synthase (iNOS) mRNA expression, phosphorylation of p38 mitogen
      activated protein kinase (p-p38), and the activation of NF kappa B. LPS-induced
      NO production and iNOS mRNA expression were inhibited by the pretreatment with
      forskolin (FSK; 5 microM) in a dose-dependent manner, and which were reversed by
      PKA inhibition by compound H89. Furthermore, LPS-induced increases of p-p38, but
      not activation of NF kappa B, were also reduced by FSK and H89 reversed the FSK
      induced inhibition response. The dose-dependent inhibition of NO production and
      iNOS mRNA expression by compound SB203580 (p38 inhibitor) suggests the
      participation of p38 in PKA-dependent inhibition of LPS-induced NO production and
      iNOS mRNA expression. However, the activation of NF kappa B by LPS also not
      affected by SB203580. Therefore, our results suggest that, in C6 glioma cells,
      LPS-induced NO production and iNOS gene expression may be regulated by PKA
      pathway through the reduction of activity of p38 kinase. This inhibitory role of
      PKA may not involve the activation of NF kappa B.

PMID- 11311972
TI  - Biochemical evidence for localization of AMPA-type glutamate receptor subunits in
      the dendritic raft.
AB  - A low density Triton-insoluble fraction with characteristic lipid composition was
      prepared from synaptic plasma membrane from the rat forebrain. The fraction was
      named dendritic raft based on its absence of the presynaptic marker
      synaptophysin, the presence of postsynaptic Glutamate receptor (GluR) subunits,
      and its resemblance to raft, caveolae-like structure. We found a differential
      distribution of NMDA-type and AMPA-type GluR subunits in the dendritic raft and
      postsynaptic density (PSD) fractions; the latter type GluR subunits were
      localized to the dendritic raft as well as PSD fraction, whereas the former type
      was mostly localized to the PSD fraction. We also found the differential
      distribution of the components of ras/mitogen-activated protein kinase (MAPK)
      pathway to the dendritic raft and PSD fractions. Dendritic raft and PSD may
      possibly interact at the postsynaptic sites for efficient signal processing that
      is required for expression of synaptic plasticity.

PMID- 11311971
TI  - Distribution of serotonin 2A, 2C and 3 receptor mRNA in spinal cord and medulla
      oblongata.
AB  - It is known that 5-HT receptors have significant roles in nociceptive and motor
      functions. We have compared the cellular localization of the mRNAs encoding
      serotonin 5-HT(2A,) 5-HT(2C,) 5-HT(3) receptor subtypes within different levels
      of the rat spinal cord and medulla. In the spinal cord, 5-HT(2C) receptor mRNA is
      expressed at high levels in most of the gray matter, except for lamina II. In
      contrast, 5-HT(2A) receptor mRNA is expressed exclusively in lamina IX. 5-HT(3)
      receptor mRNA has a low level and diffuse pattern of expression increasing
      towards the ventral horn. In both gray and white matter, there is a
      characteristic presence of a few highly stained cells. For each subtype, the
      expression pattern is similar in all four levels of the spinal cord. In the
      medulla, 5-HT(2C) receptor mRNA is at high levels in many nuclei including the
      hypoglossal nucleus, the gigantocellular reticular nucleus alpha and the
      parvocellular reticular nucleus alpha, the spinal nucleus of the trigeminal
      tract, the facial, and the dorsal medullary reticular field. Moderate to low
      levels of expression are seen in the spinal vestibular nucleus, the vagus, the
      solitary nuclei and the raphe. 5-HT(2A) receptor is expressed at high levels in
      some nuclei such as the hypoglossal nucleus, the intercalate nucleus, the
      inferior olive and the lateral reticular nucleus. Moderate to low levels of
      expression are seen in the facial, the medial vestibular nuclei, the nucleus
      ambiguous, the vagus, and the gigantocellular reticular nucleus. 5-HT(3) receptor
      mRNA is present at low levels in most of the nuclei examined, with a few
      scattered strongly labeled cells. The results show a distinct distribution of the
      three subtypes of receptors supporting their physiological roles and will help to
      understand the mechanisms of nociception and motor function.

PMID- 11311973
TI  - Attenuation of fear conditioning by antisense inhibition of brain corticotropin
      releasing factor-2 receptor.
AB  - Corticotropin releasing factor (CRF) is an important regulator of the endocrine,
      behavioral, autonomic and immune responses to stress. Two high affinity CRF
      receptors have been identified, which are distributed in distinct anatomical
      regions. CRF(1) receptors have been relatively well characterized and antagonists
      to this receptor effectively block stress-induced behaviors in rodents. The
      function of CRF(2) receptors, which are highly expressed in limbic brain regions,
      is less well understood. Therefore, an antisense oligonucleotide approach was
      used to study the role of CRF(2) receptors in the lateral septum in rats. An
      antisense oligonucleotide directed against the CRF(2) receptor mRNA reduced
      expression of CRF(2) receptors by 60--80%. In shock-induced freezing tests,
      animals administered the antisense oligonucleotide exhibited a significant
      reduction in freezing duration. However, pain sensitivity and locomotor activity
      were unaltered. A four-base mismatch of the antisense sequence had no significant
      effects on CRF(2) receptor density and on freezing behavior. These data support
      the involvement of CRF(2) receptors in fear conditioning. CRF(1) receptor
      antagonists also reduce freezing in this test. Additional studies to determine
      the effects of simultaneous inhibition of both receptor subtypes show that rats
      receiving both CRF(2) receptor antisense oligonucleotide and CRF(1) receptor
      antagonist froze significantly less than animals treated with either agent alone.
      These results provide additional evidence for the role of CRF(2) receptors in
      mediating the stress-induced actions of endogenous CRF.

PMID- 11311974
TI  - Increased mRNA expression for the alpha(1) subunit of the GABA(A) receptor
      following nitrous oxide exposure in mice.
AB  - The mechanisms by which nitrous oxide (N(2)O) produces physical dependence and
      withdrawal seizures are not well understood, but both N(2)O and ethanol exert
      some of their effects via the GABA(A) receptor and several lines of evidence
      indicate that withdrawal from N(2)O and ethanol may be produced through similar
      mechanisms. Expression levels of mRNA transcripts encoding several GABA(A)
      receptor subunits change with chronic ethanol exposure and, therefore, we
      hypothesized that N(2)O exposure would produce changes in mRNA expression for the
      alpha(1) subunit. Male, Swiss--Webster mice, 10--12 weeks of age, were exposed
      for 48 h to either room air or a 75%:25% N(2)O:O(2) environment. Brains were
      sectioned and mRNA for the alpha(1) subunit was detected by in situ hybridization
      using an 35S-labelled cRNA probe. N(2)O exposure produced a significant increase
      in expression levels of the alpha(1) subunit mRNA in the cingulate cortex, the
      CA1/2 region of the hippocampus, the dentate gyrus, the subiculum, the medial
      septum, and the ventral tegmental area. These results lend support to the
      hypothesis that N(2)O effects are produced, at least in part, through the GABA(A)
      receptor and that N(2)O produces these effects through actions in the cingulate
      cortex, hippocampus, ventral tegmental area and medial septum. These results are
      also further evidence that ethanol and N(2)O produce dependence and withdrawal
      through common mechanisms.

PMID- 11311975
TI  - Hypoxic enhancement of evoked noradrenaline release from the human neuroblastoma
      SH-SY5Y.
AB  - The effects of chronic hypoxia (2.5% O(2), 24 h) on [3H]noradrenaline ([3H]NA)
      release evoked from human neuroblastoma SH-SY5Y cells by depolarisation and by
      activation of muscarinic receptors was investigated. Depolarization of cells with
      100 mM K(+) evoked [3H]NA release, and chronic hypoxia enhanced this release
      significantly. In fluorimetric studies, the K(+)-evoked rises of [Ca(2+)](i)
      observed in response to 100 mM K(+) were also significantly enhanced. Muscarine
      evoked [3H]NA release was also dramatically enhanced by chronic hypoxia. However,
      muscarine-induced release of Ca(2+) from intracellular stores and subsequent
      capacitative Ca(2+) entry was unaffected. The protein kinase C inhibitors GF 109
      203X and RO-31-8220 did not prevent the enhancement of muscarine-evoked release
      caused by chronic hypoxia. These findings indicate that chronic hypoxia increases
      release of [3H]NA from human neuroblastoma SH-SY5Y cells. Enhancement of K(+)
      evoked release was attributable to an enhancement of depolarisation-mediated
      Ca(2+) influx. In contrast, the larger enhancement of muscarine-evoked [3H]NA
      release was not due to greater release of Ca(2+) from internal stores, nor due to
      enhanced Ca(2+) influx. Furthermore, it was not attributable to activation of
      protein kinase C. These findings suggest that enhancement of sympathetic output,
      known to occur following prolonged hypoxia, may be mediated in part by
      enhancement of exocytosis.

PMID- 11311976
TI  - NF-Y binding is required for transactivation of neuronal aromatic L-amino acid
      decarboxylase gene promoter by the POU-domain protein Brn-2.
AB  - We have previously characterized binding sites for the NF-Y transcription factor
      (-71/-52) and Brn-2 POU-domain protein (-92/-71) in the neuronal promoter of the
      human aromatic L-amino acid decarboxylase gene [Mol. Brain Res. 56 (1998) 227].
      We have now explored the functional role of these binding sites in transfected SK
      N-BE neuroblastoma cells. Mutations of the NF-Y site that abolish binding
      depressed expression of a luciferase reporter gene up to 25-fold. The
      overexpression of a dominant negative mutant of NF-YA subunit depressed
      expression by 60%. Promoter activity was increased by the overexpression of Brn
      2. Mutations or deletion of the binding site of Brn-2 did not suppress
      transcriptional activation by overexpressed Brn-2, while promoters defective in
      NF-Y binding were not transactivated by Brn-2. A GST-pulldown experiment showed
      that recombinant human Brn-2 protein weakly interacts with recombinant NF-Y
      outside of DNA. Cooperative binding of recombinant NF-Y and GST--Brn-2 proteins
      on the neuronal promoter was evidenced by an electrophoretic mobility shift
      assay. The POU-domain of Brn-2 was sufficient for such interaction. The results
      thus suggest that the activation of the neuronal promoter of the aromatic L-amino
      acid decarboxylase gene requires a direct interaction between the ubiquitous NF-Y
      factor and a cell-specific POU-domain protein. The NF-Y, but not the Brn-2
      binding site, is essential for the recruitment of the NF-Y/Brn-2 complex on the
      promoter.

PMID- 11311978
TI  - Expression of endo-oligopeptidase A in the rat central nervous system: a non
      radioactive in situ hybridization study.
AB  - Endo-oligopeptidase A (EOPA, formerly EC 3.4.22.19), a thiol-activated
      oligopeptidase, is able to degrade both bradykinin and neurotensin, and also to
      convert enkephalin-containing peptides into enkephalins. The expression of this
      enzyme was studied in the rat brain by in situ hybridization using non-radiotopic
      probes. The distribution of EOPA transcripts included many regions of the rat
      central nervous system, with higher expression in some regions, such as the
      hippocampus, cerebellum, and basal nucleus of Meynert. The marked EOPA expression
      in these areas could be anticipated, since they are rich in neuropeptides that
      are known to be EOPA substrates in vitro. The data characterize a widespread
      occurrence of EOPA in the rat brain and reinforce the suggestion of a critical
      role for EOPA in peptide processing.

PMID- 11311977
TI  - Cardiovascular responses to subseptic doses of endotoxin contribute to
      differential neuronal activation in rat brain.
AB  - The contribution of cardiovascular activity in the early central responses to
      systemic inflammation was assessed in rats following intravenous administration
      of subseptic doses of lipopolysaccharide (LPS). LPS at 12.5 microg/kg increased
      heart rate (HR) but did not alter mean arterial pressure (MAP), and induced
      interleukin-1 beta (IL-1 beta) gene expression at 1 h in circumventricular organs
      (CVOs), choroid plexus, meninges, blood vessels, and pituitary gland. IL-1 beta
      mRNA levels were attenuated at 2 h in most regions studied. LPS at 50 microg/kg
      caused a biphasic change in MAP, increased HR, increased levels of arginine
      vasopressin heteronuclear RNA in the hypothalamic paraventricular nucleus (PVN),
      and induced IL-1 beta gene expression in the nucleus of the solitary tract (NTS)
      at 1 h. LPS (both doses) induced Fos-like immunoreactivity (FLI) in the area
      postrema, organum vasculosum of the lamina terminalis, NTS, preoptic area,
      supraoptic nucleus, and PVN at 1 h. In the PVN, neurons with FLI were found
      primarily in the dorsal and dorsal medial parvocellular divisions after 12.5
      microg/kg of LPS whereas neurons with FLI were found throughout the PVN after 50
      microg/kg of LPS. After 2 h, FLI was widespread throughout the brain. Plasma ACTH
      levels were elevated at 1 and 2 h in response to both doses of LPS, and levels of
      CRF mRNA were increased after 2 h in the parvocellular PVN. Our results reveal
      that central responses to increasing doses of LPS show different patterns which
      are related to activation of distinct immune and viscerosensory pathways, and
      that cardiovascular responses contribute to early neuronal activation as LPS
      concentrations are increased.

PMID- 11311979
TI  - Regulation of aquaporin-4 expression in astrocytes.
AB  - Aquaporin-4 (AQP4), a mercury-insensitive water channel protein, is abundant in
      the central nervous system and is localized in astrocytes and ependymal cells.
      AQP4 is speculated to maintain the homeostasis of intracellular and extracellular
      water in the brain, but little is known about the mechanism of induction of its
      expression. To investigate the expressional regulation of AQP4, we analyzed
      changes in its expression during chemically induced differentiation of embryonal
      carcinoma cells (P19) to neuronal and astrocytic cells, and during the cell cycle
      of glioma cells. After exposure to retinoic acid for 4 days AQP4 mRNA expression
      started at the initiation of astrocytic differentiation of P19 cells at 6 days,
      and increased markedly by 21 days. AQP4 expression was parallel to that of GFAP,
      a marker intermediate filament of astrocytes. In glioma cell lines, AQP4 mRNA was
      not detected in the growing phase, but was induced when the cell cycle was
      arrested at G0/G1 by transient expression of p21. Although quiescent astrocytes
      in the G0/G1-phase cultured under the serum-free condition exhibited a high
      expression of AQP4, serum supplement moved them to the S-phase and markedly
      decreased the AQP expression. These results suggest that AQP4 expression may be
      induced not only at the initiation of astrocytic differentiation of neural stem
      cells, but also at the G0/G1-phase during the cell cycle of astrocytes.

PMID- 11311980
TI  - Cloning and characterization of a novel variant of rat GABA(B)R1 with a truncated
      C-terminus.
AB  - The gamma-aminobutyric acid B receptor (GABA(B)R) belong to the G-protein-coupled
      receptor superfamily and has been identified as a mediator in the transmission of
      slow inhibitory neurotransmission in the mammalian central nervous system. Two
      types of GABA(B)R have been cloned, GABA(B)R1 and R2. GABA(B)R2 is co-expressed
      with GABA(B)R1 in many brain regions and inwardly rectifying potassium channels
      are activated by GABA(B)R agonists only upon co-expression of GABA(B)R1 with
      GABA(B)R2. Several splice variants of GABA(B)R1 receptors have been cloned from
      rat brain library. Using a rat hippocampal cDNA library, we have isolated a novel
      cDNA clone of GABA(B) receptor containing an insert of 124 bp between exon 3 and
      exon 4. This insert occurred between the regions encoding the Sushi domain and
      leucine binding protein (LBP)-like domain. The insert and subsequent frame shift
      generated a cDNA that codes for a truncated polypeptide of 239 amino acids
      lacking the C-terminus. Analysis of the deduced amino acid sequence of the new
      cDNA clone, termed GABA(B)R1g, showed that it was identical to the first 157
      amino acids of GABA(B)R1a, but diverged thereafter. The C-terminal region of
      GABA(B)R1g contained two cysteine residues. GABA(B)R1g was expressed in both
      brain and peripheral tissues. Northern blot analysis demonstrated that two
      transcripts (4.5 kb and 4.0 kb) exist in hippocampus. In addition, studies of
      hippocampus in developing animals indicated that the expression of GABA(B)R1g is
      maximal at postnatal day four. GABA(B)R1g could be generated by alternative
      splicing of the GABA(B)R1 gene.

PMID- 11311981
TI  - Presynaptic N-methyl-D-aspartate receptor activation inhibits neurotransmitter
      release through nitric oxide formation in rat hippocampal nerve terminals.
AB  - In brain synapses, nitric oxide synthase activation is coupled to N-methyl-D
      aspartate-mediated calcium entry at postsynaptic densities through regulatory
      protein complexes, however a presynaptic equivalent to this signaling mechanism
      has not yet been identified. Novel evidence indicates that N-methyl-D-aspartate
      glutamate receptors may play a presynaptic role in synaptic plasticity. Thus, we
      investigated whether ionotropic glutamate receptor activation in isolated nerve
      terminals regulates neurotransmitter release, through nitric oxide formation. N
      Methyl-D-aspartate dose-dependently inhibited the release of glutamate evoked by
      4-aminopyridine (IC(50)=155 microM), and this effect was reversed by the N-methyl
      D-aspartate receptor antagonist D-(-)-2-amino-5-phosphopentanoic acid and by the
      nitric oxide synthase inhibitor, L-nitroarginine, in synaptosomes isolated from
      whole hippocampus, CA3 and CA1 areas, but not from the dentate gyrus. In
      contrast, the 4-aminopyridine-evoked release of glutamate was reduced by alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate by a nitric oxide
      independent mechanism, since it was not blocked by L-nitroarginine, and N-methyl
      D-aspartate, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or
      kainate, significantly increased cGMP formation. Presynaptic N-methyl-D-aspartate
      receptors are probably involved since removing extracellular nitric oxide with
      the scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide
      did not block the depression of glutamate release by N-methyl-D-aspartate. The
      mechanism underlying this depression involves the inhibition of synaptic vesicle
      exocytosis since N-methyl-D-aspartate/nitric oxide inhibited the release of
      [3H]glutamate and [14C]GABA evoked by hypertonic sucrose. The results also
      suggest that presynaptic N-methyl-D-aspartate receptors may function as auto- and
      heteroreceptors.

PMID- 11311982
TI  - Photoperiodic modulation of GnRH mRNA in the male Syrian hamster.
AB  - Male Syrian hamsters (Mesocricetus auratus) are seasonal breeders. They show
      marked testicular regression when exposed to short autumnal photoperiods, and
      then remain sexually quiescent for several months. By mid-winter, however, they
      show a loss in responsiveness to the inhibitory influence of short photoperiods
      and their testes begin to recrudesce. To shed light on the neuroendocrine
      mechanism responsible for mediating these reproductive changes, we examined the
      influence of photoperiod on the expression of GnRH mRNA in the hamster forebrain.
      Adult males were either exposed to short photoperiods (6L:18D) for 16 weeks or
      were maintained under long photoperiods (14L:10D); additional animals were
      exposed to short or long photoperiods for 22 weeks. As expected, exposure to
      short photoperiods for 12 weeks resulted in a marked decrease (P<0.01) in
      testicular mass and serum testosterone levels, but after 22 weeks these
      reproductive parameters were once again significantly elevated (P<0.01). In
      contrast, quantitative in situ hybridization histochemistry revealed no
      difference (P>0.05) between the GnRH mRNA levels of the short-photoperiod
      hamsters and their aged-matched long-photoperiod controls, although an age
      related decrease (P<0.05) was evident in both photoperiod-treatment groups. These
      data emphasize that GnRH mRNA is highly expressed in hamsters even when their
      reproductive axis has been rendered sexually quiescent by exposure to short
      photoperiods, and that photoperiod-induced changes in GnRH secretion, rather than
      synthesis, are more likely to regulate the timing of the breeding season. On the
      other hand, the data indicate that GnRH mRNA levels show an aging-related
      decrease, regardless of photoperiod, suggesting that in the long term a decrease
      in GnRH gene expression may contribute to the reduced fertility of old hamsters.

PMID- 11311983
TI  - Activation of p44/p42 MAP kinase in striatal neurons via kainate receptors and
      PI3 kinase.
AB  - The members of the mitogen-activated protein (MAP) kinase family -- p44/p42 MAP
      kinase (ERK), c-jun N-terminal kinase (JNK) and p38 MAP kinase (p38) are known to
      be important mediators of the physiological plasticity or neurotoxicity induced
      in the striatum by activation of ionotropic glutamate receptors. However, our
      knowledge of the class of glutamate receptor and the intracellular pathways
      involved derives totally from studies on embryonic neurons, where the mechanisms
      are likely to be totally different from those operating in mature neurons. In
      superfused striatal slices from adult rats, NMDA and kainate, but not AMPA, were
      found to activate ERK. No activation of p38 or JNK was detected following
      treatment with any ionotropic glutamate receptor agonist. The activation of ERK
      by kainate was blocked by the ERK kinase (MEK) inhibitor PD98059, and the PI3
      kinase inhibitor wortmannin, but not by the p38 MAP kinase inhibitor SB203580.
      This provides evidence for a novel pathway linking striatal kainate receptors to
      ERK activation via PI3 kinase and MEK.

PMID- 11311985
TI  - Oxidative damage to mitochondrial DNA in spinal motoneurons of transgenic ALS
      mice.
AB  - In order to clarify a possible role of oxidative stress in motoneuron death in
      amyotrophic lateral sclerosis (ALS), we examined a presence of 8-hydroxy-2
      deoxyguanosine (8-OHdG), one of the best markers of the oxidative DNA damage, in
      the spinal cord of transgenic mice harboring a mutant Cu/Zn superoxide dismutase
      (SOD1) gene. Immunocytochemistry showed a progressive accumulation of 8-OHdG in
      ventral horn neurons from early and presymptomatic stage (25 weeks) before
      significant loss of ventral horn neurons, while no detectable 8-OHdG in non
      transgenic control mice. At the late and symptomatic stage (35 weeks), the 8-OHdG
      like immunoreactivity spread over the posterior horn of spinal cord in Tg mice.
      The immunoreactivity for 8-OHdG was not localized in the nucleus but in cytoplasm
      with small granular pattern. These data suggest that an oxidative damage to
      mitochondrial DNA is happening in spinal motoneurons of the Tg mice from very
      early stage of the disease, and may be involved in the mechanism of the
      subsequent motoneuron death in this model.

PMID- 11311984
TI  - Caspase mRNA expression in a rat model of focal cerebral ischemia.
AB  - Proteins of the caspase family are involved in the signalling pathway that
      ultimately leads to programmed cell death (apoptosis), which has been reported to
      occur in some experimental models of stroke. In a previous paper we used
      quantitative reverse transcription and polymerase chain reaction (RT-PCR) to
      characterise changes in the mRNA expression of one member of this family, caspase
      3, in a rat model of permanent focal ischemia. Here we have used this technique
      to study the expression of a further three caspases which are involved in
      different aspects of caspase signalling. Caspase-8, involved in Fas-mediated
      apoptosis, was upregulated in the cortex of ischemic rats. Caspase-11, which
      leads to the synthesis of the functional form of the cytokine interleukin-1 beta,
      also showed increased expression, but with a different temporal profile from
      caspase-8. In contrast, caspase-9, which forms part of the pathway signalling
      through the mitochondria, showed a decrease in expression. The expression of a
      further four caspases (1, 2, 6 and 7) has also been characterised in a simpler
      experiment. These caspases all showed distinctive patterns of expression
      following the induction of ischemia. These data lead us to conclude that caspase
      expression as a whole is under very strict transcriptional control in this model.
      Certain elements of caspase signalling, such as the Fas-induced pathway and the
      events upstream of IL-1 beta processing, are upregulated, while others are not.
      This may be due to some form of genetic program activated in response to ischemia
      in the brain and may highlight which biological pathways are modulated.

PMID- 11311986
TI  - Effects of prolonged wakefulness on c-fos and AP1 activity in young and old rats.
AB  - Recent studies have demonstrated that the immediate-early gene c-fos is induced
      in neuronal populations responsible for specific sleep-wake states. The induction
      of this gene may be functionally relevant to sleep homeostasis since without the
      gene mice (c-fos null) take longer to fall asleep and have a selective reduction
      in slow-wave sleep. This suggests that a build-up of c-fos during wakefulness
      increases the drive to sleep and lack of c-fos is associated with reduced sleep.
      Sleep also has an effect on c-Fos serving to eliminate the protein rapidly.
      Waxing and waning of transcription factors such as c-Fos may influence slow,
      oscillating events such as sleep and wakefulness. To further examine what role c
      Fos may play in regulating sleep, the present study examined the effects of
      prolonged wakefulness on c-Fos and AP-1 activity in young (3.5 months old) and
      old (21.5 months old) Sprague--Dawley rats. Previously we found that old rats
      slept less even after prolonged wakefulness, and other investigators have found
      that aging is also associated with a decline in c-Fos. In the present study, we
      reasoned that prolonged wakefulness would also fail to increase c-Fos in old
      versus young rats. The baseline levels of c-Fos and AP-1 activity were not
      different between young and old rats. However, in response to 6 or 12 h of
      prolonged wakefulness, old rats demonstrated significantly less c-Fos and AP-1
      activity compared to young rats. These findings suggest that in old rats the
      mechanism responsible for c-Fos induction in response to wakefulness is
      deficient. Such a decline at the molecular level could contribute to the decline
      in sleep that typically occurs with age.

PMID- 11311987
TI  - A disintegrin and metalloprotease with thrombospondin type1 motifs (ADAMTS-1) and
      IL-1 receptor type 1 mRNAs are simultaneously induced in nerve injured motor
      neurons.
AB  - Following rat hypoglossal nerve injury, expression of mRNAs for a disintegrin and
      metalloprotease with thrombospondin type1 motifs (ADAMTS-1) and IL-1 receptor
      type 1 (IL-1RT1) are induced in the injured motor neurons. Although N1E-115 (N1E)
      cells, which were treated with IL-1 alpha, showed no alteration of ADAMTS-1 mRNA
      expression, a substantial increase of ADAMTS-1 mRNA expression was observed in
      the N1E cells expressing IL-1RT1. These findings suggest that nerve injury
      promotes IL-1RT1 expression in the injured neurons and thereby ADAMTS-1
      transcription was induced in response to IL-1 released from glial cells.

PMID- 11311989
TI  - Roles of lipid polymorphism in intracellular delivery.
AB  - Lipids, which adopt nonbilayer phases, have fascinated researchers as to the
      functional roles of these components in biomembranes. In particular, lipids
      capable of adopting the hexagonal H(II) phase have received considerable
      attention because of the observation that such lipids can promote membrane
      fusion. In the rational design of lipid-based delivery systems, H(II) phase
      lipids have been employed to endow systems with fusogenic, membrane-destabilizing
      properties. We will outline the molecular basis for the polymorphic phase
      behavior of lipids and highlight some of the uses of nonbilayer lipids in the
      preparation of lipid-based delivery systems. In addition, a distinction will be
      drawn between lipid-based systems which rely on the inclusion of nonbilayer
      lipids for activity, and systems which contain components which actively promote
      formation of nonbilayer structure within biological membranes.

PMID- 11311990
TI  - Amphotericin B colloidal dispersion: an improved antifungal therapy.
AB  - Amphotericin B colloidal dispersion (ABCD) is a near 1:1 discoidal complex of
      amphotericin B (AMB) and sodium cholesteryl sulfate (SCS) arranged as a bilayer
      of SCS interspersed with AMB via noncovalent interactions. The complex is stable
      in blood and plasma with minimal dissociation. In vitro and in vivo studies show
      that ABCD is as effective and four to five times safer than conventional AMB
      (CAB) for fungal infection. Compared with CAB treatment, ABCD demonstrates
      reduced peak plasma levels, prolonged residence time, and lowered AMB levels in
      most tissues including kidney, the major target of toxicity for CAB. In 572
      patients with systemic fungal infections secondary to severe underlying disease,
      ABCD doses < or = 6 mg/kg/day were well tolerated, even in those who failed to
      tolerate or respond to CAB. Mild-to-moderate, dose-dependent, infusion-related
      adverse events typically seen with CAB were also observed with ABCD, with no sign
      of renal or hepatic toxicity. Complete or partial recovery was seen in 57.3%.
      Therefore, ABCD should be considered as an alternative treatment of systemic
      fungal infections.

PMID- 11311991
TI  - Solid lipid nanoparticles: production, characterization and applications.
AB  - Solid lipid nanoparticles (SLN) have attracted increasing attention during recent
      years. This paper presents an overview about the selection of the ingredients,
      different ways of SLN production and SLN applications. Aspects of SLN stability
      and possibilities of SLN stabilization by lyophilization and spray drying are
      discussed. Special attention is paid to the relation between drug incorporation
      and the complexity of SLN dispersions, which includes the presence of alternative
      colloidal structures (liposomes, micelles, drug nanosuspensions, mixed micelles,
      liquid crystals) and the physical state of the lipid (supercooled melts,
      different lipid modifications). Appropriate analytical methods are needed for the
      characterization of SLN. The use of several analytical techniques is a necessity.
      Alternative structures and dynamic phenomena on the molecular level have to be
      considered. Aspects of SLN administration and the in vivo fate of the carrier are
      discussed.

PMID- 11311992
TI  - Exogenous surfactant as a drug delivery agent.
AB  - Pulmonary surfactant is a complex mixture of lipids and several specific
      surfactant proteins, which together render it with unique spreading properties
      and a dynamic surface tension behavior. These characteristics are heralded as
      ideal for a carrier of choice to instil therapeutic agents into the lung, because
      this combination enables high local therapeutic levels while minimizing systemic
      side-effects of the instilled agent. This review outlines the rationale to use
      exogenous surfactant in lung injury, including opening-up inaccessible regions of
      the lung to other therapeutic agents. Especially the combination of anti
      microbial agents and surfactant offers an alternative for critically ill patients
      with pneumonia. Some caution is also indicated in combining surfactant with
      antibiotics without proper evaluation of possible interactions. Some other
      applications for surfactant as a carrier are discussed. Overall, the benefits of
      surfactant as a carrier warrants clinical trials and promises additional
      therapeutic tools for the clinician.

PMID- 11311993
TI  - Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical
      research.
AB  - The specific properties of fluorocarbons, exceptional chemical and biological
      inertness, high gas-dissolving capacity, low surface tension, excellent spreading
      characteristics and high fluidity, have triggered numerous applications of these
      compounds in oxygen delivery. An injectable emulsion of fluorocarbon-in-water
      destined to deliver oxygen to tissues at risk of hypoxia has now completed Phase
      III clinical trials in Europe. A neat fluorocarbon is currently investigated in
      Phase II for treatment of acute respiratory failure by liquid ventilation.
      Fluorinated lipids and fluorinated surfactants can be used to elaborate and
      stabilize various colloidal systems, including different types of emulsions,
      vesicles and tubules, that also show promise for controlled release drug
      delivery.

PMID- 11311994
TI  - Cubic phase gels as drug delivery systems.
AB  - Lipids have been used extensively for drug delivery in various forms such as
      liposomes, and solid-matrices. The focus of this review is evaluation of liquid
      crystalline cubic phases, spontaneously formed when amphiphilic lipids are placed
      in aqueous environment, for drug delivery. Cubic phases have an interesting
      thermodynamically stable structure consisting of curved bicontinuous lipid
      bilayer in three dimensions, separating two congruent networks of water channels.
      The unique structure of cubic phase has been extensively studied using various
      spectroscopic techniques and their resemblance to biomembranes has prompted many
      scientists to study behavior of proteins in cubic phases. The ability of cubic
      phase to incorporate and control release of drugs of varying size and polar
      characteristics, and biodegradability of lipids make it an interesting drug
      delivery system for various routes of administration. Cubic phases have been
      shown to deliver small molecule drugs and large proteins by oral and parenteral
      routes in addition to local delivery in vaginal and periodontal cavity. A number
      of different proteins in cubic phase appear to retain their native conformation
      and bioactivity, and are protected from chemical and physical inactivation
      perhaps due to the reduced activity of water and biomembrane-like structure of
      cubic phase. Release of drugs from cubic phase typically show diffusion
      controlled release from a matrix as indicated by Higuchi's square root of time
      release kinetics. Incorporation of drug in cubic phase can cause phase
      transformation to lamellar or reversed hexagonal phase depending on the polarity
      and concentration of the drug, which may affect the release profile.
      Biodegradability, phase behavior, ability to deliver drugs of varying sizes and
      polarity and the ability to enhance the chemical and/or physical stability of
      incorporated drugs and proteins make the cubic phase gel an excellent candidate
      for use as a drug delivery matrix. However, shorter release duration and the
      extremely high viscosity may limit its use to specific applications such as
      periodontal, mucosal, vaginal and short acting oral and parenteral drug delivery.

PMID- 11311995
TI  - Recombinant lipoproteins: lipoprotein-like lipid particles for drug targeting.
AB  - Lipoproteins are endogenous particles that transport lipids through the blood to
      various cell types, where they are recognised and taken up via specific
      receptors. These particles are, therefore, excellent candidates for the targeted
      delivery of drugs to various tissues. For example, the remnant receptor and the
      asialoglycoprotein receptor (ASGPr), which are uniquely localised on hepatocytes,
      recognise chylomicrons and lactosylated high density lipopoteins (HDL),
      respectively. In addition, tumour cells of various origins overexpress the low
      density lipoprotein (LDL) receptor that recognises apolipoprotein E (apoE) on
      small triglyceride-rich particles and apoB-100 on LDL. Being endogenous,
      lipoproteins are biodegradable, do not trigger immune reactions, and are not
      recognised by the reticuloendothelial system (RES). However, their endogenous
      nature also hampers large-scale pharmaceutical application. In the past two
      decades, various research groups have successfully synthesised recombinant
      lipoproteins from commercially available natural and synthetic lipids and serum
      derived or recombinant apolipoproteins, which closely mimic the metabolic
      behaviour of their native counterparts in animal models as well as humans. In
      this paper, we will summarise the studies that led to the development of these
      recombinant lipoproteins, and we will address the possibility of using these
      lipidic particles to selectively deliver a wide range of lipophilic, amphiphilic,
      and polyanionic compounds to hepatocytes and tumour cells. In addition, the
      intrinsic therapeutic activities of recombinant chylomicrons and HDL in sepsis
      and atherosclerosis will be discussed.

PMID- 11311996
TI  - Cationic lipid-DNA complexes in gene delivery: from biophysics to biological
      applications.
AB  - Great expectations from the application of gene therapy approaches to human
      disease have been impaired by the unsatisfactory clinical progress observed.
      Among others, the use of an efficient carrier for nucleic acid-based medicines is
      considered to be a determinant factor for the successful application of this
      promising therapeutic strategy. The drawbacks associated with the use of viral
      vectors, namely those related with safety problems, have prompted investigators
      to develop alternative methods for gene delivery, cationic lipid-based systems
      being the most representative. This review focuses on the various parameters that
      are considered to be crucial to optimize the use of cationic lipid-DNA complexes
      for gene therapy purposes. Particular emphasis is devoted to the analysis of the
      different stages involved in the transfection process, from the biophysical
      aspects underlying the formation of the complexes to the different biological
      barriers that need to be surpassed for gene expression to occur.

PMID- 11311997
TI  - A Phase I safety and immunogenicity trial of UBI microparticulate monovalent HIV
      1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human
      subjects.
AB  - Thirty-three HIV-seronegative adults were recruited into a Phase I safety and
      immunogenicity HIV-1 vaccine trial. The immunogens were as follows: a synthetic,
      monovalent, octameric HIV-1 MN V3 peptide in aluminum hydroxide (alum) adjuvant
      administered by intramuscular delivery; and a similar product encapsulated in
      biodegradable micro-spheres composed of co-polymers of lactic and glycolic acids,
      administered by the oral route. These were administered in three sequential oral
      doses, followed by a parenteral boost. No serious adverse experiences were
      observed. Oral administration of this vaccine, alone or in combination with
      parenteral boosting, resulted in no significant humoral, cellular, or mucosal
      immune responses.

PMID- 11311999
TI  - Immunostimulatory sequence up-modulate the interaction between immunoglobulins
      and plasmid DNA at acidic pH.
AB  - To identify specific receptors for immunostimulatory sequence (ISS), a cDNA
      library of human bone marrow was screened by one-hybrid system using ISS as bait.
      Among four duel-positive clones isolated so far, two encode light chain of
      immunoglobulin (Ig) homologous to anti-DNA and anti-HBsAg (HBsAb), respectively,
      suggesting a direct interaction between ISS and Igs. ELISA revealed that HBsAb,
      as well as Igs in normal mouse serum and a monoclonal anti-v5 antibody, bound to
      plasmid DNA in a pH-dependent way; more importantly, the plasmids inserted with
      more copies of ISS shown higher reactivity with these Igs than their blank
      vectors. Electrophoretic mobility shift assay (EMSA) showed HBsAb bound to
      oligonucleotides (ODN) also in a pH-dependent and ISS-specific way. Furthermore,
      ISS-containing ODN could enhance the binding of Igs to plasmid DNA at acidic pH.
      These results support existence of direct ISS-Ig interaction and demonstrated
      that DNA-Ig interaction could be up-modulated by ISS. In consideration of the
      crucial role of membrane Ig (mIg) in B cell activation, these results suggest mIg
      may be a candidate ISS receptor in ISS-induced B cell activation.

PMID- 11311998
TI  - Comparison of antibody kinetics following meningococcal serogroup C conjugate
      vaccine between healthy adults previously vaccinated with meningococcal A/C
      polysaccharide vaccine and vaccine-naive controls.
AB  - Few data are available on the kinetics of meningococcal serogroup C-specific
      antibody production following meningococcal serogroup C conjugate (MCC)
      vaccination, particularly in those who have received prior meningococcal A/C
      polysaccharide (MACP) vaccination(s). Laboratory staff who had previously
      received either one dose (n = 35), two doses (n = 18) of MACP vaccine or who were
      naive to previous meningococcal vaccination (n = 42) were vaccinated with MCC.
      Bloods were taken pre-vaccination, on the subsequent 4 days and on days 10 and
      28. Serogroup C serum bactericidal antibody (SBA), and anti-serogroup C-specific
      IgG, IgM and IgA were measured. There were no significant differences between the
      groups who had received either 2 or 1 prior dose(s) of MACP, therefore, these
      results were combined. Up to day 4 there was no evidence of a significant
      increase or decrease in the median levels of SBA, IgG, IgM or IgA in either the
      naive or MACP groups, although about 20% of individuals did have 4-fold SBA rises
      by day 4. By day 10 there were large significant increases in the levels of SBA,
      IgG, IgM and IgA with respective fold increases from pre-vaccination levels of
      4.6, 1.9, 1.2 and 2.1 in the MACP group and 270, 13.4, 4.8 and 33.8 in the naive
      group. Further significant increases were seen between day 10 and 28 for SBA, IgG
      and IgM (naive group only). By day 28, 4-fold SBA rises had occurred in 63.5% of
      the MACP group and 97.6% of the naive group. The SBA GMT on day 28 significantly
      differed between the naive and MACP groups with GMTs 2.8-fold higher in the naive
      group (P = 0.021). In conclusion, no decline in serogroup C-specific antibody
      levels was demonstrated immediately post-MCC vaccination whilst these levels had
      risen significantly by day 10. Putative protective SBA titres (> or =8, 32 or
      128) were observed by day 10 following MCC vaccination regardless of MACP
      history.

PMID- 11312000
TI  - The adjuvant effect of synthetic oligodeoxynucleotide containing CpG motif
      converts the anti-Haemophilus influenzae type b glycoconjugates into efficient
      anti-polysaccharide and anti-carrier polyvalent vaccines.
AB  - Synthetic oligodeoxynucleotides containing CpG immunostimulatory sequences (ISS)
      have been shown to act as potent adjuvants of type 1 immune responses when co
      administered with protein or peptide vaccines. We have recently shown that ISS
      can increase the anti-polysaccharide (CHO) and anti-tetanus toxoid (TT) or anti
      diphtheria (CRM) toxoid antibody levels if used as adjuvant of anti-Haemophilus
      influenzae type b (Hib) CHO vaccine conjugated with TT or CRM. The analysis of
      anti-TT and anti-CRM IgG subclasses showed a significant increase in IgG2a, IgG2b
      and/or IgG3 in the presence of ISS. Anti-TT and anti-CRM antibodies were shown to
      neutralize the activity of both the tetanus and diphtheria toxin in vivo or in
      vitro tests respectively. These data show that ISS have the potential to increase
      host antibody response against both the CHO and the protein component of a
      conjugated vaccine, and encourage the investigation to identify strategies of
      vaccination with schedules aimed at the valuation of protein carriers as
      protective immunogens.

PMID- 11312001
TI  - DNA vaccination by immersion and ultrasound to trout viral haemorrhagic
      septicaemia virus.
AB  - This work reports preliminary data on the application of a novel method,
      ultrasound, for the DNA vaccination of rainbow trout. First, the best
      formulations were selected that increased the transfer by immersion of a plasmid
      coding for the green fluorescent protein (GFP) gene into trout fry.
      Quantification of GFP expression by fluorescence in the fin cells was used to
      study time course, DNA concentration dependence and comparison of different
      formulations. The best GFP expression results were obtained with short pulses of
      ultrasound, DOTAP liposomes and recombinant bacteria or bactofection. Other
      liposomes or microencapsulation formulations resulted in a GFP fluorescence
      similar to background values. Second, DNA immersion-vaccination of
      immunocompetent fingerling trout with the selected formulations was performed by
      using a plasmid coding for the glycoprotein G gene of the viral haemorrhagic
      septicaemia virus (VHSV). The immunization of fingerling trout was estimated by
      measuring humoral antibody, lymphoproliferation and VHSV challenge responses.
      Short pulses of low intensity ultrasound were the only method by which both
      humoral antibody responses and survival after VHSV challenge were obtained.
      Immersion DNA-vaccination using short pulses of ultrasound could eventually lead
      to a practical way to vaccinate small fish.

PMID- 11312002
TI  - The epidemiology of herpes zoster and potential cost-effectiveness of vaccination
      in England and Wales.
AB  - The epidemiology of herpes zoster and post-herpetic neuralgia (PHN) was
      quantified from a variety of data sources and the potential cost-effectiveness of
      vaccination assessed. The annual incidence and severity of zoster increases
      sharply with age, as measured by physician consultation and hospitalisation
      rates, average length of stay, average proportion of cases developing PHN and the
      age-specific case-fatality ratio. Combining these data with information on health
      related quality of life results in an estimated loss of 20000 quality adjusted
      life years (QALYs) annually in England and Wales from herpes zoster (17400 due to
      PHN). The current cost of treating herpes zoster associated disease is estimated
      to be 47.6m pounds annually. Since both the health and economic burden are high,
      vaccination of the elderly is expected to be cost-effective under most scenarios,
      the attractiveness of immunisation increasing with age due to the increased
      burden of disease in the very elderly.

PMID- 11312003
TI  - Collagen minipellet as a controlled release delivery system for tetanus and
      diphtheria toxoid.
AB  - The use of biodegradable polymer matrices as a single-dose vaccine delivery
      system was investigated using tetanus toxoid (TT) and diphtheria toxoid (DT).
      BALB/c mice were immunized with TT or DT in different formulations including
      individual, in minipellet and aluminum hydroxide (alum), and the antibody
      responses were monitored for 48 weeks. Antigens entrapped in minipellet elicited
      higher antibody responses compared to those obtained with individual antigens and
      antigens adsorbed to alum and the antibody levels remained elevated over 48
      weeks. In addition, minipellet formulations induced the same subclasses of
      antibodies induced by alum formulations. These results raise the possibility to
      obtain optimal and long-lasting immune responses by a single administration of
      minipellet formulations.

PMID- 11312004
TI  - Age-specific seroprevalence to varicella-zoster virus: study in Swiss children
      and analysis of European data.
AB  - Up to date epidemiological data provide the rationale for potential varicella
      immunization strategies in Europe. The scope of this study was: (1) to generate
      new seroprevalence data by evaluating sera of 970 individuals aged 0-16 years for
      the presence of IgG against Varicella-zoster virus (VZV); and (2) to review
      existing seroprevalence data. Of 256 individuals >12 years of age, 96.1% (95%
      confidence interval [CI], 93.7-98.5) were seropositive. Swiss citizens > 12 years
      of age were less likely to be seronegative than foreign citizens (2.3 vs. 15.4%;
      odds ratio, 0.17; CI, 0.05-0.58). The age-specific seroprevalence curve
      demonstrated a peak at 7 years of age (84.9%; CI, 75.2-94.5) followed by lower
      rates at 8 and 9 years. A peak at 7-10 years of age was found in all previously
      reported seroprevalence curves (chi(2)-test for trend of pooled data, P = 0.09;
      Poisson analysis, P < 0.001). It is concluded that: (1) > 90% of individuals in
      Europe acquire immunity against VZV before adolescence; (2) there is no evidence
      for a recent upward shift of the age at primary varicella; and (3) there may be a
      north-to-south gradient of seroprevalence. The peak at 7-10 years may represent a
      transient loss of detectable antibody by some individuals.

PMID- 11312005
TI  - Vaccination of Balb/c mice against experimental visceral leishmaniasis with the
      GP36 glycoprotein antigen of Leishmania donovani.
AB  - Leishmania donovani GP36 glycoprotein is the main antigen of the FML Fucose
      Mannose Ligand (FML) complex specifically recognized by sera of kala-azar human
      patients. The GP36 was isolated by chemical elution + sonication and used for
      Balb/c mouse vaccination in combination with saponin, by the s.c. route, inducing
      a strong and specific protective effect against experimental visceral
      leishmaniasis shown by the increase of: specific IgG antibodies (82.6%), mainly
      IgG2a, the delayed type of hypersensitivity to promastigote lysate (37.8%, P <
      0.001), the in vitro cellular proliferative response to GP36 of ganglia
      lymphocytes (53.5%, P < 0.005) and the decrease of liver parasite burden (68.1%,
      P < 0.025). Saponin treated controls reacted significantly differently from GP36
      vaccinated animals at all the assayed variables (P < 0.05). GP36 induced
      significant protection against murine visceral leishmaniasis at concentrations
      commonly used for vaccination with recombinant antigens.

PMID- 11312006
TI  - Recombinant Semliki Forest virus vector exhibits potential for avian virus
      vaccine development.
AB  - The Semliki Forest virus (SFV) expression system was evaluated as a basis for
      avian vaccine development. Initial studies indicated that 1-day-old specific
      pathogen-free (SPF) chicks were susceptible to infection with an infectious
      strain of SFV, producing SFV-specific antibodies but no clinical disease. One-day
      old SPF chicks immunised intramuscularly with recombinant replication-defective
      SFV (rSFV) particles expressing the Escherichia coli (E. coli) lacZ reporter gene
      developed high titres of beta-gal- specific antibodies at 4 weeks p.i. after two
      inoculations. In contrast, significantly lower antibody levels were elicited in
      chicks immunised with a recombinant SFV-based DNA construct or a conventional CMV
      promoter-based DNA plasmid. rSFV particles encoding the protective VP2 protein or
      the VP2/VP4/VP3 polyprotein of infectious bursal disease virus (IBDV) were
      produced and the expressed antigens were characterised in cell culture. Proteins
      of the correct size were generated and found to react against a range of IBDV
      specific monoclonal antibodies. Immunisation of 1-day-old SPF chicks with rSFV
      particles encoding the IBDV proteins resulted in specific antibodies being
      elicited in all birds, neutralising antibodies being induced in some but not all
      birds.

PMID- 11312007
TI  - Immunological implications of structural mimicry between a dodecapeptide and a
      carbohydrate moiety.
AB  - The immunogenicity and antibody cross-reactivity of two chemically different but
      structurally equivalent molecular mimics were analyzed by presenting them to the
      immune system in different modes. The observed differences in IgM and IgG
      responses in terms of cross-reactivity with the mimicking antigen could reflect
      the differential proliferative abilities of the corresponding B-cells.
      Modification of the T-cell help, either by using a promiscuous T-cell epitope or
      by prepriming, led to the shift in the antibody response towards the mimicking
      epitope. Also, the anti-sugar antibodies could be boosted using a carbohydrate
      mimicking peptide on cross-immunization. Thus, the carbohydrate-peptide mimicry
      appears to be a topological quasi-equivalence reflected differently in terms of
      antibody response during maturation.

PMID- 11312008
TI  - Long-term persistence of cellular immunity to Oka vaccine virus induced by
      pernasal co-administration with Escherichia coli enterotoxin in mice.
AB  - A mutant of Escherichia coli enterotoxin induced cellular immunity to a live
      varicella vaccine (the Oka strain) as a mucosal adjuvant in mice. The persistence
      of this cellular immunity was investigated. A commercially available live Oka
      vaccine virus and toxin were administered once simultaneously via the nasal
      route, in mice. Ten or 12 months later, a delayed-type hypersensitivity to the
      vaccine virus was detected by footpad test, but an antibody neutralizing the
      varicella-zoster virus was not. When spleen cells from mice immunized with the
      vaccine and toxin were re-stimulated by live vaccine in vitro, their thymidine
      uptake and IL-2 production were higher than those from mice immunized with the
      vaccine alone, but lower than those of spleen cells prepared from mice 2 months
      after nasal administration. Production of IL-4 in these cells, however, was not
      induced by re-stimulation in vitro. These results suggest that although humoral
      immunity for Oka vaccine virus is only weakly induced by one co-administration of
      the vaccine and toxin, cellular immunity is induced and maintained over 1 year,
      though it declines with age. The nasal administration of the vaccine and toxin
      might be effective for maintaining cellular immunity to the varicella-zoster
      virus long term.

PMID- 11312009
TI  - Immunogenicity and reactogenicity of a single dose of a diphtheria--tetanus-
      acellular pertussis component vaccine (DTaP) compared to a diphtheria--tetanus
      toxoid (Td) and a diphtheria toxoid vaccine (d) in adults.
AB  - We compared immunogenicity and reactogenicity of a single dose of DTaP vaccine
      (containing tetanus and diphtheria toxoids and four acellular pertussis antigens)
      with conventional Td- or d-vaccines in 180 German adults. Antibody values against
      diphtheria and tetanus toxin and against the pertussis antigens fimbriae (FIM),
      filamentous hemagglutinin (FHA) and pertussis toxin (PT) were measured in pre-
      and post-immunization sera. Reactogenicity was determined by a patient diary
      card. Pre-immunization antibody values against diphtheria toxin were low in all
      three vaccine groups. After immunization, > or = 80% of the vaccinees in all
      three groups were fully protected (> or = 0.1 IU/ml), but geometric mean values
      were significantly higher in DTaP recipients compared to Td or d recipients (1.65
      vs. 0.44 and 0.48, respectively; both P < 0.05). Pre-immunization antibody values
      against tetanus toxin were high in all three groups, and after immunization 100%
      of the vaccinees were protected (> or = 0.1 IU/ml). Furthermore, substantial
      antibody responses against pertussis antigens were elicited in DTaP recipients
      with geometric mean rises of 22.5, 4.1 and 7.5 for antibodies against FHA,
      fimbriae and PT, respectively. All three vaccines were well tolerated. Frequency
      and severity of local reactions were similar between DTaP and Td recipients and
      even less common in d recipients. Since DTaP did provide a significant boost of
      anti-pertussis antibodies and a significantly higher anti-diphtheria response
      than conventional Td vaccine without an increase of side effects, it might be an
      appropriate candidate for use in adults.

PMID- 11312010
TI  - Autovaccination of dairy cows to treat post partum metritis caused by Actinomyces
      pyogenes.
AB  - Autovaccines are therapeutic vaccines manufactured from a disease causing micro
      organism for individual treatment of patients, animals, or sometimes herds to
      treat chronic or recurrent infections. Despite the common use of autovaccines in
      veterinary medicine, their mechanism of action, i.e. the immunologic effector
      mechanism activated after administration, has never been investigated. Here we
      present data concerning the use of autovaccines to treat metritis infection in a
      group of dairy cows. Following autovaccination we observed a significant decrease
      in CD4+ cells paralleled by an increase in T-cells expressing the gammadelta-T
      cell receptor (gammadelta-TCR) in the peripheral blood of the treated animals.
      Lymphocyte proliferation assays showed an initial increase in antigen-specific
      responsiveness followed by a decrease in this responsiveness during
      autovaccination treatment. We therefore conclude that administration of an
      autovaccine leads to the activation of immunologic effector mechanisms which
      contribute to recovery of the diseased animals.

PMID- 11312011
TI  - Physicochemical and immunological characterization of hepatitis B virus envelope
      particles exclusively consisting of the entire L (pre-S1 + pre-S2 + S) protein.
AB  - The hepatitis B virus (HBV) envelope (env) protein is composed of three regions;
      the 108- or 119-residue pre-S1 region involved in the direct interaction with
      hepatocytes, the 55-residue pre-S2 region associated with the polymerized albumin
      mediated interaction, and the major 226-residue S protein region. Thus, to
      improve the immunogenic potency of conventional HB vaccines, development of a new
      vaccine containing the entire pre-S1 region in addition to pre-S2 and S is
      desired. We previously reported the efficient production of the HBV env L (pre-S1
      + pre-S2 + S) protein in the recombinant yeast cells [J Biol Chem 267 (1992)
      1953]. In this study, the HBV env L protein produced as nano-particles in yeast
      has been purified and characterized. By equilibrium sedimentation, an average
      molecular weight of L particle was estimated to be approximately 6.4 x 10(6),
      indicating that about 110 molecules of L proteins are assembled into an L
      particle. By atomic force microscopy in a moist atmosphere, the L particles were
      observed as large spherical particles with a diameter of 50-500 nm. The L
      particles were stable on short-time heating at a high temperature and long-time
      storage at a low temperature but rather unstable on repeated freezing and thawing
      and treatment with dithiothreitol. When immunized in mice, L particles elicited
      efficiently and simultaneously the anti-S, anti-pre-S2, and anti-pre-S1
      antibodies. The ED(50) values in mice for the anti-S and anti-pre-S2 antibodies
      were similar to those elicited by the M (pre-S2 + S) particles. Furthermore, the
      anti-pre-S1 rabbit antibodies were found to recognize various segments of the pre
      S1 region, including the pre-S1 (21-47) segment. These results show the high
      ability of L particles to induce all antibodies against HBV env proteins, hence
      promising the future application of L particles for the next generation HB
      vaccine.

PMID- 11312012
TI  - Persistence of immunologic memory for 13 years in recipients of a recombinant
      hepatitis B vaccine.
AB  - All subjects in this clinical study gave informed written consent, and guidelines
      of the authors' institution regarding human experimentation were observed in the
      conduct of the study. A booster dose of vaccine given to 18 adolescents
      (immunized as children) and 7 older adults immunized 13 years earlier with a 3
      dose course of recombinant hepatitis B vaccine induced a strong secondary
      antibody response, demonstrating that the vaccinees retained immunologic memory
      for HbsAG. Within one week, booster vaccination induced an 11 to 24-fold rise in
      the GMT of anti-HBs which continued, reaching 52 to 319-fold after 4 weeks.
      Significantly even the 5 individuals with less than 10 mIU/ml of anti-HBs prior
      to the booster all had impressive responses to the booster dose.

PMID- 11312013
TI  - Protection against Leishmania donovani infection by DNA vaccination: increased
      DNA vaccination efficiency through inhibiting the cellular p53 response.
AB  - DNA-vaccination holds great promise for the future of vaccine development against
      infectious diseases, especially in developing countries. We therefore
      investigated the possibility of using DNA-vaccination against Leishmania donovani
      infection with the A2 virulence gene and whether inhibiting the cellular p53
      response could increase the effectiveness of the A2 DNA vaccine. p53, also known
      as the guardian of the genome, is activated following DNA transfection and has
      pleotropic effects on cells, which could have adverse effects on the
      effectiveness of DNA-vaccination. Two major observations are reported within.
      First, vaccination with the A2 gene induced both humoral and cellular immune
      responses against A2 which provided significant protection against infection with
      L. donovani. Second, inhibition of p53 with human papillomavirus E6 resulted in
      higher expression of heterologous transfected genes in vitro and more efficient
      DNA-vaccination in vivo. These results have important implications for DNA
      vaccination against leishmaniasis and potentially against other infectious
      diseases.

PMID- 11312014
TI  - Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur)
      in human volunteers.
AB  - A randomized, controlled, double-blinded study was conducted to determine safety
      and immunogenicity of five live attenuated dengue vaccines produced by Aventis
      Pasteur (AvP). The study was completed with 40 flavivirus non-immune volunteers:
      five recipients of each monovalent (dengue-1, dengue-2, dengue-3, or dengue-4)
      vaccine, ten recipients of tetravalent (dengue-1, dengue-2, dengue-3, and dengue
      4) vaccine, and ten recipients of vaccine vehicle alone. All vaccines were
      administered in a single subcutaneous dose (range, 3.6-4.4 log(10) plaque forming
      units). No serious adverse reactions occurred in volunteers followed for 6 months
      after vaccination. Five vaccine recipients developed fever (T > or = 38.0 degrees
      C), including four tetravalent vaccinees between days 8 and 10 after vaccination.
      Dengue-1, dengue-2, dengue-3, or dengue-4 vaccine recipients reported similar
      frequency of mild symptoms of headache, malaise, and eye pain. Tetravalent
      vaccinees noted more moderate symptoms with onset from study days 8-11 and
      developed maculopapular rashes distributed over trunk and extremities. Transient
      neutropenia (white blood cells < 4000/mm3) was noted after vaccination but not
      thrombocytopenia (platelets < 100,000/mm3). All dengue-3, dengue-4, and
      tetravalent vaccine recipients were viremic between days 7 and 12 but viremia was
      rarely detected in dengue-1 or dengue-2 vaccinees. All dengue-2, dengue-3, and
      dengue-4, and 60% of dengue-1 vaccine recipients developed neutralizing and/or
      immunoglobulin M antibodies. All tetravalent vaccine recipients were viremic with
      dengue-3 virus and developed neutralizing antibodies to dengue-3 virus. Seven
      volunteers also had multivalent antibody responses, yet the highest antibody
      titers were against dengue-3 virus. The AvP live attenuated dengue virus vaccines
      are safe and tolerable in humans. The live attenuated tetravalent dengue vaccine
      was most reactogenic, and preferential replication of dengue-3 virus may have
      affected its infectivity and immunogenicity.

PMID- 11312015
TI  - Effect of physico-chemical modification on the immunogenicity of Haemophilus
      influenzae type b oligosaccharide-CRM(197) conjugate vaccines.
AB  - Haemophilus influenzae type b (Hib) poly-ribosyl-ribityl phosphate (PRP)
      oligosaccharide-CRM(197) conjugate vaccines from two different manufacturers (Hib
      A and Hib B) were subjected to adverse storage conditions and used to establish
      correlates between physico-chemical characteristics and immunogenicity. There
      were manufacturer-specific differences in the effect of freezing or freeze
      thawing on the carrier protein conformation and the anti-CRM(197) or anti-PRP IgG
      response in rabbits whereas both conjugates showed similar stability when stored
      at elevated temperatures. Both oligosaccharide-CRM(197) conjugate vaccines formed
      apparent 'aggregates' of non-specifically associated higher molecular weight
      material when subjected to elevated temperatures or repeated freeze-thawing.
      Following subcutaneous injection of samples into CBA mice and New Zealand White
      rabbits, the amount of IgG raised against CRM(197) was significantly lower for
      samples incubated at 37 or 55 degrees C compared with those kept at 4 degrees C,
      consistent with the less well-folded conformation of the carrier protein observed
      at elevated temperatures. Moreover, there was a parallel reduction in the amount
      of IgG raised against PRP and the level of bactericidal antibodies induced by
      vaccines A and B stored at 55 degrees C consistent with the observed
      depolymerisation of the oligosaccharide chains. Carrier protein conformational
      changes resulting from storage under adverse conditions did not affect the
      immunogenicity to Hib PRP in laboratory animals unless associated with loss of
      bound saccharide presumably because the carrier protein retains continuous T(H)
      cell epitopes which are unaffected by conformational changes.

PMID- 11312016
TI  - Comparison of neuropathogenicity of poliovirus type 3 in transgenic mice bearing
      the poliovirus receptor gene and cynomolgus monkeys.
AB  - To clarify the similarities of poliovirus infection in cynomolgus monkeys and
      transgenic mice bearing the poliovirus receptor, TgPVR21, we compared the
      pathological changes of these animals following intraspinal inoculation of two
      strains of poliovirus type 3 using immunohistochemical detection of the capsid
      antigen. All of the monkeys inoculated with 10(6) TCID(50) viruses showed flaccid
      paralysis 2 or 3 days post-inoculation (p.i.). TgPVR21 mice showed paralysis
      starting from 2 to 3 days p.i. Histologically, neurons having pyknotic nuclei and
      eosinophilic cytoplasm and neuronophagia were characteristically observed in both
      animals, but central chromatolysis was not observed in infected TgPVR21. The
      median lesion scores in the monkeys and TgPVR21 were well correlated, though the
      distribution of poliovirus-infected lesions in the central nervous system was
      different. In both animals the motor neurons and the brainstem nuclei responsible
      for flaccid paralysis were infected by the virus, while the cerebral cortex and
      thalamus were infected in the monkeys but not in TgPVR21. These results confirmed
      the reliability of neurovirulence tests using TgPVR21 as a substitute for
      monkeys, in respect to the spinal and brainstem lesions of poliovirus type 3.

PMID- 11312017
TI  - Plasmid DNA encoding caprine interferon gamma inhibits antibody response to
      caprine arthritis-encephalitis virus (CAEV) surface protein encoded by a co
      administered plasmid expressing CAEV env and tat genes.
AB  - This study characterized immune responses of Saanen goats co-immunized with pUC18
      based plasmids expressing caprine arthritis-encephalitis virus (CAEV) rev-env
      (pENV) or tat-rev-env (pTAT-ENV) and a second plasmid encoding caprine interferon
      gamma (IFNgamma). A previous study reported that immunization with pENV or pTAT
      ENV induces IgG2 biased antibody responses to plasmid encoded CAEV surface
      envelope protein (SU). We show here that regional lymph nodes (LN) of pENV and
      pTAT-ENV immunized goats contain a dominant subset of SU activated IFNgamma+ Th1
      lymphocytes. Co-immunization with pENV or pTAT-ENV and a caprine IFNgamma cDNA
      expression plasmid (pcIFNgamma) did not potentiate activation of SU responsive
      Th1 lymphocytes. However, the antibody response to SU encoded by pTAT-ENV was
      inhibited by co-immunization with pcIFNgamma. Results indicate that synergistic
      effects of CAEV Tat and IFNgamma suppress the primary adaptive B cell response to
      plasmid encoded SU.

PMID- 11312018
TI  - Immunogenicity in mice of pneumococcal glycoconjugate vaccines using pneumococcal
      protein carriers.
AB  - Antibody response and protective immunity were evaluated in mice immunized with
      pneumococcal glycoconjugate vaccines using two pneumococcal protein carriers.
      Mice injected with type 9V polysaccharide (PS) conjugated to inactivated
      pneumolysin (Ply) or autolysin (Aly) produced high levels of IgG and IgM
      antibodies to both the PS and the protein carrier. Higher PS antibody titers to
      the pneumococcal PS conjugates were measured by ELISA using PS-Ply or PS-tetanus
      toxoid (TT) conjugate as a coating antigen compared with PS mixed with methylated
      human serum albumin. Type 9V PS (10 microg) inhibited most of the 9V IgM and IgG
      antibody binding to the 9V-TT coated plate. In contrast, absorption with 19F PS
      did not inhibit 9V antibody binding. The avidity index of IgG antibodies in the
      9V PS-Ply serum was 55.5 +/- 0.9, compared with 47.8 +/- 1.4 for 9V PS-Aly serum.
      Thus, high avidity of serum antibodies in conjugate-immunized mice can provide
      more effective functional activity for protection against pneumococcal infection.
      Mice immunized with these glycoconjugates exhibited rapid bacterial clearance
      from blood and provided cross-protection against challenge with heterologous
      serotypes of virulent pneumococci. These results reveal that conjugates using
      pneumococcal protein carriers can induce opsonophagocytic activity to destroy
      homologous and heterologous pneumococci, indicating that such conjugates can
      confer broader protective immunity than conjugates using non-pneumococcal
      proteins.

PMID- 11312019
TI  - Identification of CD4+ T cell epitopes on the fusion (F) and attachment (G)
      proteins of bovine respiratory syncytial virus (BRSV).
AB  - To gain insight into the antigenic structure of the F and G proteins of BRSV, we
      have mapped CD4+ T cell epitopes on these proteins using synthetic peptides and
      lymphocytes from vaccinated, naturally infected or experimentally infected
      calves, in proliferation assays. Bovine CD4+ T cells recognised epitopes that
      were distributed predominantly within the F1 subunit of the F protein, some of
      which were adjacent to previously identified B cell epitopes. Bovine CD4+ T cell
      epitopes within the G protein were mainly located within the cytoplasmic tail.
      Several immunodominant bovine T cell epitopes within the F protein, that were
      recognised by calves with different haplotypes, are also recognised by human T
      cells. Thus, cattle and humans appear to recognise similar T cell epitopes on the
      F protein. Studies using antibodies to bovine MHC class II and BoLA DR
      transfected CHO cells as antigen-presenting cells indicated that immunodominant
      regions of the F and G proteins contained both DR- and DQ-restricted epitopes.
      The finding that there was little recognition of the extracellular domain of the
      G protein by T cells has important implications for vaccine design based on the
      soluble form of this protein.

PMID- 11312020
TI  - Efficacy of a human anthrax vaccine in guinea pigs, rabbits, and rhesus macaques
      against challenge by Bacillus anthracis isolates of diverse geographical origin.
AB  - The efficacy of a licensed human anthrax vaccine (Anthrax Vaccine Adsorbed (AVA))
      was tested in guinea pigs, rabbits, and rhesus macaques against spore challenge
      by Bacillus anthracis isolates of diverse geographical origin. Initially, groups
      of Hartley guinea pigs were vaccinated at 0 and 4 weeks with AVA, then challenged
      intramuscularly at 10 weeks with spores from 33 isolates of B. anthracis.
      Survival among the vaccinated groups varied from 6 to 100%, although there were
      no differences in mean time to death among the groups. There was no correlation
      between isolate virulence and variable number tandem repeat category or
      protective antigen genotype identified. New Zealand white rabbits were then
      vaccinated with AVA at 0 and 4 weeks, and challenged at 10 weeks by aerosol with
      spores from six of the isolates that were highly virulent in vaccinated guinea
      pigs. AVA completely protected the rabbits from four of the isolates, and
      protected 90% of the animals from the other two isolates. Subsequently, two of
      these six isolates were then used to challenge rhesus macaques, previously
      vaccinated with AVA at 0 and 4 weeks, and challenged at 10 weeks by aerosol. AVA
      protected 80 and 100% of the animals from these two isolates. These studies
      demonstrated that, although AVA confers variable protection against different B.
      anthracis isolates in guinea pigs, it is highly protective against these same
      isolates in both rabbits and rhesus macaques.

PMID- 11312021
TI  - Analysis of Bordetella pertussis isolates collected in Japan before and after
      introduction of acellular pertussis vaccines.
AB  - Because of recent concern that whole-cell pertussis vaccination can drive
      antigenic divergence of circulating isolates of Bordetella pertussis, we compared
      12 clinical isolates of B. pertussis collected in Japan, the first country to
      introduce acellular pertussis vaccines, with the vaccine strain. We used pulsed
      field gel electrophoresis, sequencing of ptx and prn genes and expression of
      fimbriae. Most of the isolates collected before or after introduction of
      acellular vaccine possess similar restriction patterns. They contain ptx genes
      and prn alleles similar to the vaccine strain and to European isolates collected
      before the introduction of vaccination. Two recently collected isolates
      exhibiting a different pulsed-field gel electrophoresis pattern possess ptxS1 and
      prn alleles similar to the alleles harbored by European isolates circulating
      currently. Our preliminary results suggest that, if acellular pertussis vaccine
      induced antigenic divergence exists, it is likely to be a slow or rare process.

PMID- 11312022
TI  - Acceptable protective efficacy of influenza vaccination in young military
      conscripts under circumstances of incomplete antigenic and genetic match.
AB  - Commercial inactivated parenteral influenza vaccines reduced febrile (> or = 38
      degrees C) respiratory illness by 53% (95% CL: 41-63%) during a 3 week outbreak
      in 1998 when A/Sydney/5/97(H3N2)-like influenza viruses were shown to be the
      predominant etiological agents and an older antigenic variant, A/Nanchang/933/95,
      served as the vaccine virus. The calculatory efficacy for preventing
      virologically diagnosed influenza infections was 57% (95% CL: 40-68%). The study
      population consisted of 1374 young male military conscripts. Vaccination coverage
      on a voluntary basis was 67%. Vaccination was ineffective in preventing febrile
      illness during a second epidemic wave lasting 2 weeks when mainly adenoviruses
      were shown to have been circulating in the garrison. Out of the 36 nasopharyngeal
      aspirates positive for influenza A by antigen detection, 18 A/Sydney/5/97-like
      strains (10 from non-vaccinated and eight from vaccinated subjects) and two
      A/Nanchang/933/95-like strains (both from non-vaccinated subjects) were isolated
      in MDCK cell cultures. Intraepidemic variation was detected among the
      A/Sydney/5/97-like field strains in their HA1 sequences and reactivity in HI
      tests, but no evidence was obtained that this variation would have been of
      significance to the virus in breaking through the vaccination-induced immunity.

PMID- 11312023
TI  - An inactivated bovine virus diarrhoea virus (BVDV) type 1 vaccine affords
      clinical protection against BVDV type 2.
AB  - This study was designed to answer to two distinct questions. Firstly, is it
      possible to reproduce clinical signs of acute bovine virus diarrhoea virus (BVDV)
      type 2 infection including signs of haemorrhagic disease under experimental
      conditions in cattle at 20 weeks of age? Secondly, what is the extent of the
      protection afforded by vaccination with an inactivated BVDV type 1 vaccine
      against BVDV type 2 infection? Calves were vaccinated at 12 and 16 weeks of age
      with a commercially available inactivated BVDV type 1 vaccine (Bovilis BVD). At
      20 weeks they were challenge infected with BVDV type 2 virus together with
      unvaccinated control calves. The unvaccinated animals developed typical signs of
      respiratory disease, diarrhoea with erosions and haemorrhages along the whole
      length gastro-intestinal tract, and depletion of lymphocytes in lymphatic organs.
      These signs were either absent or markedly less severe in the vaccinated animals.
      The beneficial effects of vaccination were most striking in the haematological
      parameters thrombocytopenia and leukopenia. It can be concluded that vaccination
      with Bovilis BVD affords cross-protection against clinical effects of a challenge
      infection with heterologous type 2 BVDV.

PMID- 11312024
TI  - Contribution of MHC class I-dependent immune mechanisms induced by attenuated
      recombinant Salmonella typhimurium secreting superoxide dismutase to protection
      against murine listeriosis.
AB  - A recombinant (r)Salmonella typhimurium aroA strain secreting the naturally non
      secreted superoxide dismutase (SOD) of Listeria monocytogenes controls murine
      listeriosis dependent on 'transporter associated with antigen processing' (TAP)
      mediated immune mechanisms. TAP1-deficient mice (devoid of most CD8 T cells)
      vaccinated with this rSalmonella SODs strain succumbed to lethal L. monocytogenes
      challenge, whereas C57BL/6 mice were protected by this vaccine. Moreover,
      vaccination of H-2I-Abeta-deficient mice (lacking major histocompatibility class
      (MHC) II molecules and thus devoid of mature CD4 TCR-alphabeta cells), of TAP1
      deficient as well as of beta2microglobulin-deficient mice (devoid of conventional
      CD8 T cells) with a sublethal dose of L. monocytogenes and subsequent challenge
      with rSalmonella control or SODs strain revealed contribution of both MHC class I
      and MHC class II-dependent immune mechanisms to the control of secondary
      Salmonella infection. Finally, the clearance of rSalmonella SODs bacteria was
      achieved in TAP1-deficient animals vaccinated with L. monocytogenes. Our data
      suggest a role of TAP-dependent mechanisms in priming of protective immunity by
      rSalmonella micro-organisms secreting SOD.

PMID- 11312025
TI  - A strong association between HLA-DR9 and gelatin allergy in the Japanese
      population.
AB  - The frequency of HLA class I and II phenotypes was determined among 23 patients
      with positive gelatin IgE, eight of whom developed anaphylaxis, 18 patients who
      did not have gelatin IgE but who experienced non-immediate reactions after
      exposure to gelatin. HLA-DR9, which is unique to Orientals, was present in 56.5%
      of the gelatin IgE positive patients, as compared to control population frequency
      of 24% (P < 0.002). In the non-immediate reaction group, who did not generate
      IgE, phenotype distribution resembled controls. HLA-DR9 positive individuals have
      a relative risk of 4.1 for developing gelatin allergy with positive IgE.

PMID- 11312026
TI  - Vaccination with the glycoprotein D gene of pseudorabies virus delivered by
      nonpathogenic Escherichia coli elicits protective immune responses.
AB  - Attenuated intracellular bacteria, such as Salmonella and Shigella, have been
      exploited to act as gene delivery vectors. In this study, we report that
      nonpathogenic, live Escherichia coli can be used for the delivery of DNA vaccines
      in vivo, leading to generation of immune responses against plasmid-encoded
      foreign antigens. The pseudorabies virus (PrV) DNA vaccine carrying the
      glycoprotein D (gD) gene delivered by E. coli was able to induce protective
      immune responses in mice against a lethal PrV challenge. Co-delivery of E. coli
      carrying plasmid DNA encoding prothymosin alpha enhanced cellular immune
      responses to the PrV DNA vaccine delivered by E. coli. Our results suggest that
      nonpathogenic E. coli may be used as a vector for DNA vaccines in veterinary
      uses.

PMID- 11312027
TI  - Immune responses and protection obtained with rotavirus VP6 DNA vaccines given by
      intramuscular injection.
AB  - Intramuscular (i.m.) injection of murine VP6 DNA vaccines raised high titers of
      rotavirus-specific serum IgG and IgA antibodies in BALB/c mice. A Th1-like
      antibody response was generated based on the ratio of serum IgG2a to IgG1
      antibodies. Rotavirus-specific serum IgA but not fecal IgA was detected in mice
      prior to rotavirus challenge. Partial protection against rotavirus challenge was
      achieved as measured by reduction of rotavirus antigen shedding in feces. A
      similar level of protection was found with a bovine rotavirus VP6 DNA vaccine
      against a murine rotavirus challenge, suggesting that heterologous protection can
      be obtained by immunizing with VP6 DNA vaccines. We did not directly test for
      cytotoxic T lymphocyte (CTL) activity, but in vivo depletion of CD8+ T cells in
      mice immunized with a murine VP6 DNA vaccine did not significantly change the
      duration of virus shedding or the pattern of protection obtained. This finding
      suggested that CD8+ CTL activity was not essential for the partial protection we
      obtained by i.m. immunization of mice with VP6 DNA vaccines.

PMID- 11312028
TI  - A novel microencapsulated peptide vaccine against hepatitis B.
AB  - A 48 amino acid synthetic peptide (S121/48) representing residues 121-167 of the
      major envelope protein of hepatitis B virus (HBsAg) was successfully encapsulated
      into polylactide co-glycolide microspheres. A single immunization of the
      microspheres in BALB/c (H-2d) mice resulted in the production of high-titre anti
      HBs antibodies (IgG1-type). The response was long lasting and was superior to
      that obtained using the same peptide adjuvanted with Freund's complete adjuvant.
      A T-cell memory response was detected 10 weeks after a booster immunization
      (approximately 35 weeks after initial immunization) as measured by in-vitro re
      stimulation of splenocytes. This study illustrates the feasibility of a single
      dose vaccine for hepatitis B and is, to our knowledge, the first demonstration of
      a synthetic peptide immunogen inducing anti-native protein antibodies of
      comparable titre to those obtained with conventional vaccines for hepatitis B.
      The suitability of a synthetic peptide vaccine for hepatitis B is discussed.

PMID- 11312029
TI  - Liposome-mediated DNA vaccination: the effect of vesicle composition.
AB  - Liposome-entrapped DNA has been shown to enhance the potency of DNA vaccines,
      possibly by facilitating uptake of the plasmid by antigen-presenting cells (APC).
      In this paper, we have investigated the influence of the liposomal composition
      and surface charge on such potency. Plasmid DNA pRc/CMV HBS encoding the S
      (small) region of hepatitis B surface antigen was entrapped within cationic
      liposomes of various compositions and surface charges with high efficiency (88
      97% of the amount used) by the dehydration-rehydration method that generates
      dehydration-rehydration vesicles (DRV). Cryo-electron microscopy revealed that
      DNA-containing DRV (DRV(DNA)) were multilamellar. In immunisation studies, female
      Balb/c mice were given two to four intramuscular injections of 10 microg naked or
      liposome-entrapped pRc/CMV HBS and bled at time intervals. Results indicate that
      the lipid composition of the DRV(DNA) influences the strength of the humoural
      response (immunoglobulin (Ig)G subclasses) with inclusion of dioleoyl
      phosphatidylethanolamine (DOPE) or phosphatidylethanolamine (PE) in the liposomal
      structure contributing to greater responses. DRV(DNA) in which the DOPE or PE
      were omitted or substituted with cholesterol led to significant reduction of
      humoural responses against the encoded antigen. Replacing phosphatidylcholine
      (PC) in the DRV(DNA) with the high-melting distearoyl phosphatidylcholine also
      contributed to lower responses. In other experiments, IgG responses were
      monitored in mice immunised with pRc/CMV HBS entrapped in DRV composed of PC and
      DOPE as before but incorporating increasing amounts of DOTAP (1-16 micromol).
      Maximal IgG responses were observed at 10 weeks after the first of four
      injections and suggested a trend of higher responses when 4 or 8 micromol DOTAP
      was present in the DRV(DNA) formulation. Cell-mediated immunity (measured in
      terms of endogenous antigen-specific splenic interferon-gamma) in mice immunised
      with pRc/CMV HBS entrapped in liposomes composed of PC, DOPE and DOTAP (16:8:4
      molar ratio) was much greater than in animals treated with naked plasmid. These
      results indicate that liposome-mediated DNA immunisation is more effective than
      the use of naked DNA, and also suggest that the presence of fusogenic
      phosphatidylethanolamine in DRV in conjunction with a low-melting
      phosphatidylcholine and an appropriate content of cationic lipid might contribute
      to more effective liposomal DNA vaccines. The notion that liposomes improve
      immune responses to the plasmid-encoded vaccine by facilitating the latter's
      uptake by APC was supported by the observation that in Balb/c mice injected
      intramuscularly with liposome-entrapped pCMV. Enhanced green fluorescent protein,
      expression of the gene in terms of fluorescence intensity in the draining lymph
      nodes, was much greater than in animals treated with the naked plasmid.

PMID- 11312031
TI  - Induction of thymidine kinase in mouse skin exposed to 12-O-tetradecanoylphorbol
      13-acetate.
AB  - Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibited an
      increase in the epidermal thymidine kinase (TK) activity in a dose dependent
      manner. Maximum induction of TK was observed at a TPA concentration of 2.5 microg
      per animal. The induction of TK by TPA appeared to be a function of time with the
      maximum TK induction between 4 and 16 h after TPA application. Repeated
      applications of TPA every 24 h did not show any cumulative effect rather TK
      activity appeared to be normal after two applications. However, repeated
      applications of TPA at an interval of 48 h exhibited increased TK activity even
      after 16 applications. Cycloheximide and actinomycin D, the inhibitors of protein
      and RNA synthesis, inhibited the TPA induced activation of TK. Our results
      demonstrated that TPA induced the TK activity may be, by increasing de novo
      synthesis of enzyme protein and this induction might lead to increased de novo
      DNA synthesis after TPA application. DMBA was used as a reference compound. As
      far as the authors are aware, this is the first report on TK induction by topical
      application of TPA.

PMID- 11312032
TI  - Ochratoxin A in human serum samples collected in Isparta-Turkey from healthy
      individuals and individuals suffering from different urinary disorders.
AB  - Ochratoxin A (OA) is a nephrotoxic fungal metabolite (mycotoxin) occurring in
      foodstuffs. The compound is causally associated with mycotoxin porcine
      nephropathy, a disease comparable with a human kidney disease called endemic
      nephropathy. In this paper OA levels in the human serum samples collected from
      healthy individuals and individuals suffering from different urinary disorders in
      Isparta-Turkey are presented. OA was measured in serum samples of 40 healthy
      people and a total of 93 patients with different kinds of urinary disorders. Four
      different kinds of urinary disorders were represented: chronic renal failure
      treated by hemodialysis (35), chronic renal failure treated by peritoneal
      dialysis (28), patients with bladder cancer (15), patients with renal stones
      (15). Analysis of OA in human blood samples was performed using an analytical
      method based on the measurement of fluorescence spectra. The mean concentration
      of OA in the healthy group was 0.4 +/- 0.28 ng/ml. The highest mean concentration
      was found in the group of patients treated by hemodialysis, 2.1+/- 1.2 ng/ml. The
      mean concentrations of the toxin in all patients groups were higher compared to
      the control group. Also, a significant difference was found between the mean
      concentrations of the groups of patients treated by dialysis (hemodialysis or
      peritoneal dialysis) and of the patients with renal stones or bladder cancer,
      only with the exception of the difference between peritoneal dialysis and renal
      stones group. No other significant differences were found when comparing the two
      groups. The findings indicate that OA may have a role in the human urinary
      pathology considered herein. A higher level of OA in dialysis groups compared to
      the control, renal stones and bladder cancer groups could probably be explained
      by the reduced glomerular filtration rate of these patients.

PMID- 11312033
TI  - Genotoxic effect of hydroquinone on the cultured mouse spleenocytes.
AB  - The daily administration of 0, 0.5, 1, 2, 4 and 8 mg/kg b. wt. of hydroquinone
      (HQ) to Swiss albino mice, consecutively for 6 days resulted in a dose dependent
      elevation in the frequency of micronucleated binucleate spleenocytes (MNBNS).
      This increase in the frequency of MNBNS was significantly higher than that of non
      drug treated controls (0 mg/kg). The daily administration of various doses of HQ
      for 6 days not only increased the frequency of binucleated spleenocytes bearing
      one micronuclei (MN), but also the BNS bearing two, three, and four MN. The study
      demonstrates that the daily administration of various doses of HQ for 6 days
      increases the genotoxic and mutagenic potential in mice.

PMID- 11312034
TI  - Effects of neonatal exposure to a high-dose p-tert-octylphenol on the male
      reproductive tract in rats.
AB  - Time-course alterations in morphological changes of the reproductive tract
      including spermatogenesis as well as pituitary and gonadal hormones, reproductive
      ability, and the size of the sexually dimorphic nucleus of the preoptic area (SDN
      POA) were investigated in male rats neonatally exposed to 100 mg/kg p-tert
      octylphenol (OP) subcutaneously. OP treatment affected hormone levels of follicle
      stimulating hormone (FSH) and testosterone, reproductive organ weights and sperm
      counts. Slightly depressed FSH levels at prepuberty and prolonged suppression of
      testosterone till 7 weeks of age were observed as two hormonal alterations. The
      lasting reduction in testosterone appeared to be associated with growth
      inhibition of male reproductive organs such as the testis, prostate and
      epididymis, these demonstrating low organ weights compared with those of age
      matched controls till 7 weeks of age. The FSH concentrations after puberty showed
      a rise to values equal to or higher than those of the control group, suggesting
      recovery of maturation of the reproductive tract. No morphological abnormalities,
      even with morphometric stage analysis of spermatogenesis, were detected in the
      male reproductive tract throughout the study. Size of the SDN-POA and
      reproductive ability was comparable to those in controls. At the termination (18
      weeks of age), however, a reduction in the sperm count in the epididymis of OP
      treated animals demonstrated a possibility that the male reproductive system
      might be still affected by neonatal exposure to OP. The results observed
      demonstrate that neonatal exposure to a high-dose OP exerts estrogenic action
      directly or indirectly, resulting in slight but prolonged impairment of the male
      reproductive tract. The suppression of FSH caused by modulation of the
      hypothalamus-pituitary control system may be the trigger for the impairment,
      while the possibility of direct estrogenic action of OP is not ruled out. Our
      results also indicate that more sensitive endpoints should be established to
      detect the effects of neonatal exposure to estrogens or estrogenic compounds on
      the male reproductive tract.

PMID- 11312035
TI  - Effects on male rats of di-(2-ethylhexyl) phthalate and di-n-hexylphthalate
      administered alone or in combination.
AB  - The effects of phthalate esters of branched chain alcohols, typified by di-(2
      ethylhexyl)phthalate (DEHP) differ from those of esters of straight chain
      alcohols typified by di-n-hexyl phthalate (DnHP). The former induce liver
      enlargement and proliferation of hepatic peroxisomes, while the latter cause no
      peroxisome proliferation but cause fat accumulation in the liver. Both classes of
      phthalate esters are hypolipidaemic and cause thyroid changes associated with an
      increased rate of thyroglobulin turnover. As phthalate esters are used as
      mixtures, we have examined the effect of mixtures of the compounds. Groups of
      five male Wistar albino rats were administered either control diet or diets
      containing either 10000 ppm of DEHP, 10000 ppm of DnHP or 10000 ppm DEHP plus
      10000 ppm DnHP for 14 days. Rats receiving diets containing DEHP showed the
      expected increase in relative liver weight, in "peroxisomal" fatty acid oxidation
      and in CYP4A1. Serum triglyceride and serum cholesterol were also reduced, and
      the thyroid showed the histological changes mentioned above. Rats consuming diets
      containing DnHP showed no increase in relative liver weight and no induction of
      peroxisomal fatty acid oxidation or CYP4A1. However, there was a marked
      accumulation of fat in the liver. The fall in serum cholesterol was similar to
      that in rats treated with DEHP, but the fall of serum triglyceride was more
      pronounced. Thyroidal changes were again observed. In general, changes in rats
      treated with a mixture of DEHP and DnHP were very similar to those found with
      rats treated with DEHP alone. The liver was enlarged, and peroxisomal fatty acid
      oxidation and CYP4A1 were both induced. The amount of fat in the liver was much
      less than in rats receiving DnHP alone. Thyroid changes were similar to those in
      rats receiving the individual compounds. The effect on serum cholesterol seemed
      additive, but the levels of serum triglyceride were intermediate between the
      groups receiving the single compounds.

PMID- 11312036
TI  - Potentiation of arsenic-induced cytotoxicity by sulfur amino acid deprivation
      (SAAD) through activation of ERK1/2, p38 kinase and JNK1: the distinct role of
      JNK1 in SAAD-potentiated mercury toxicity.
AB  - Sulfur amino acid deficiency occurs in certain pathophysiological situations
      (e.g. protein-calorie malnutrition). Previous studies revealed that sulfur amino
      acid deprivation (SAAD) activated MAP kinases and potentiated cadmium-induced
      cytotoxicity by activation of ERK1/2 in conjunction with p38 kinase or JNK. The
      present study was designed to determine susceptibility of cells to a variety of
      heavy metals in combination with SAAD. Viability was assessed in H4IIE cells
      treated with sodium arsenite, mercuric chloride, sodium selenite, lead acetate,
      chromium trioxide or manganese chloride. SAAD potentiated the cytotoxicity of
      H4IIE cells by arsenic or mercury (i.e. EC50, 19 and 5 microM in SAAD vs. 401 and
      42 microM in control medium, respectively). TUNEL assays revealed that the
      potentiated arsenic or mercury toxicity involved apoptotic cell death. Lead or
      selenite moderately elicited cell death, which was not enhanced by SAAD. Chromium
      or manganese caused no significant cytotoxicity. Treatment of cells with U0126
      [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] an ERK1/2 inhibitor
      or SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H
      imidazole] a p38 kinase inhibitor effectively prevented SAAD-potentiated arsenic
      toxicity. The potentiated arsenic toxicity was also inhibited in cells stably
      expressing a dominant negative mutant of c-Jun N-terminal kinase 1 [JNK1(-)]. The
      inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 kinase
      failed to prevent mercury-induced toxicity enhanced by SAAD. JNK1(-) cells were
      minimally susceptible to mercury in SAAD medium. These results demonstrated that
      SAAD potentiated cytotoxicity induced by arsenic or mercury and that activation
      of ERK1/2, p38 kinase and JNK1 was responsible for the potentiated arsenic
      toxicity, whereas the mercury toxicity enhanced by SAAD was mediated with the
      activity of JNK1.

PMID- 11312037
TI  - Donors of NO and pulsed radiation at lambda = 820 nm exert effects on cell
      attachment to extracellular matrices.
AB  - The adhesion of HeLa cells to a glass matrix was evaluated after the irradiation
      of the cell suspension with a pulsed near-infrared light-emitting diode (lambda =
      820 nm, frequency 10 Hz, dose 8-120 J/m(2)) and treatment with two donors of
      nitric oxide, sodium nitroprusside (SNP, 5 x 10(-4) M) and NaNO(2) (4 x 10(-4)
      M). It was found that in an irradiated cell suspension, the cell-glass adhesion
      increases in a dose-dependent manner (a bell-shaped curve with a maximum at 60
      J/m(2)). The treatment of cells with SNP or NaNO(2) before the irradiation
      eliminates the radiation-induced attachment stimulation. Pretreatment of cells
      with SNP not only eliminates the radiation-induced attachment stimulation but
      inhibits the attachment of irradiated (but not non-irradiated) cells. It is
      suggested that a modulation of the activity of respiratory chain (probably the
      alteration of the activity of cytochrome c oxidase) is involved in radiation
      induced increase of cell attachment.

PMID- 11312038
TI  - Effect of mild whole body hyperthermia on cytotoxic action of N-methyl-N'-nitro-N
      nitrosoguanidine in Swiss mice.
AB  - Studies were carried out to ascertain the efficacy of mild whole body
      hyperthermia (WBH) as a modifier of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      cytotoxicity in mice. Adult Swiss male mice, 6-8 weeks old, weighing about 25 g
      were exposed to mild WBH (39 degrees C, 1 h) in a precision temperature
      controlled environmental chamber maintained at 50-60% relative humidity. Twenty
      four hours after treatment, animals were administered with different doses of
      MNNG either by intraperitoneal (i.p.) injections or by feeding through drinking
      water and were monitored for survival. The studies revealed that the exposure of
      animals to mild WBH, 24 h prior to MNNG administration results in an increase in
      survival and recovery in mean body weight compared with those administered with
      MNNG only. This suggests that prior WBH treatment can effectively reduce the MNNG
      cytotoxicity in mice.

PMID- 11312039
TI  - Comparing the clastogenic potential of atrazine with caffeine using Chinese
      hamster ovary (CHO) cells.
AB  - The agronomically important herbicide atrazine has been reported to cause damage
      to animal chromosomes at levels of atrazine found contaminating drinking water
      supplies. While documenting potential chromosome damage is important it is
      equally important to compare the damage with the potential consequences of
      compounds readily found in our food and water supply. In this study atrazine and
      caffeine, a ubiquitous food additive, were compared at equal levels and at real
      exposure levels for their ability to damage animals chromosomes in cell culture.
      Nuclei and chromosomes from treated and control cells were analyzed by flow
      cytometry. At extremely low levels, atrazine was found to be a more potent
      clastogen. Caffeine had no effect on the chromosomes at the lower levels. Both
      chemicals were genotoxic at the potential exposure levels with caffeine being
      more disruptive than atrazine. Atrazine appears to be a more potent damaging
      agent than caffeine at similar levels of exposure; however, the levels of
      caffeine one is exposed to during everyday life appears to be more damaging on
      the endpoints analyzed in this study than the levels of atrazine found
      contaminating water supplies. The advantages and limitations of whole cell
      clasotgenicity are also presented in light of these results.

PMID- 11312040
TI  - Isolated airway exposure to toluene diisocyanate results in skin sensitization.
AB  - Toluene diisocyanate (TDI), a highly reactive industrial chemical is a leading
      cause of occupational asthma in westernized countries. It has also been reported
      to be a skin sensitizer in mice and guinea pigs although instances of skin
      sensitivity in humans are rare. It is uncertain if skin-contact is necessary to
      initiate the dermal sensitization. This study sought to determine if exclusive
      airway exposure to TDI could result in skin sensitivity. A group of guinea pigs
      was administered 50 microl of 0.6% TDI intratracheally (it.), another group
      received intranasal (in.) application of 0.6, 1.2, or 1.8% TDI. Eighty percent
      (4/5) of the it.-dosed animals, and 92% (11/12) of in.-dosed animals exhibited
      skin sensitivity. None of 14 control animals gave a positive reaction to patch
      challenge with TDI. These findings indicate that exclusive exposure of the
      airways to TDI can result in skin sensitivity and suggest that such events may be
      possible in TDI workers and should be considered in all workers exposed via the
      airways to chemical sensitizers.

PMID- 11312041
TI  - An attempt to employ the Zung Self-Rating Depression Scale as a "lab test" to
      trigger follow-up in ambulatory oncology clinics: criterion validity and
      detection.
AB  - We examined issues of criterion validity and detection of depression employing
      the Zung Self-Rating Depression Scale (ZSDS) as a "lab test" to trigger follow-up
      interviews of ambulatory oncology patients by oncology staff and the possibility
      of subsequent algorithm-based antidepressant treatment. Sixty oncology patients
      were screened with the ZSDS and then interviewed using the Mini-International
      Neuropsychiatric Interview (MINI). We examined the sensitivity and specificity of
      various cutoffs on the ZSDS and a briefer version, the Brief Zung Self-Rating
      Depression Scale (BZSDS) as they predicted results of the MINI, which was used as
      the criterion. Mean age of patients was 58.3 years (SD = 11.9). Thirty-two were
      female (53.3%) and 28 were male (46.7%). The correlation of the ZSDS (r = -0.66,
      P <.0001) and BZSDS (r = -0.57, P <.0001) with the MINI overall suggested
      acceptable levels of criterion validity. Additionally, we examined various cutoff
      scores on the ZSDS and BZSDS to explore the false negative and false positive
      rates that are associated with each. For example, using the mild cutoff on the
      Zung (score > 48) to determine depression or adjustment disorder, 14 false
      negatives and 2 false positives were found. When the more stringent moderate
      cutoff (score > 56) was used, 25 false negatives and 0 false positives were
      found. Oncology staff can utilize such data to make decisions about where to set
      cut-offs that trigger follow-up based on the amount of error that is allowable in
      their attempts to identify depressive symptoms in their patients. We discuss that
      such decisions might be based on many factors including the resources available
      in a particular site for follow-up or the comfort of particular oncologists and
      nurses managing and prescribing psychotropic medications, or in providing
      supportive counseling.

PMID- 11312042
TI  - Effects of high dose opioids and sedatives on survival in terminally ill cancer
      patients.
AB  - Concerns that high dose opioids and sedatives might shorten patient survival
      could contribute to insufficient symptom alleviation for terminally ill cancer
      patients. To examine the effects of opioids and sedatives prescribed in the final
      48 hours on patient survival, a re-analysis of the prospectively collected data
      was performed on 209 hospice inpatients. Patient characteristics and clinical
      symptoms were prospectively recorded, and information about the use of opioids
      and sedatives in the last two days was collected by a chart review. Opioids were
      prescribed in 82% of the patients, with a median dose of 80 mg oral morphine
      equivalent (OME)/48 hours. Sixty percent received some sedative medications,
      mainly haloperidol (43% of total sample, 7.5 mg/48 hours), midazolam (23%,
      23mg/48 hours), and hydroxyzine (15%, 50 mg/48 hours). There were no significant
      differences in survival between the patients who received different doses of
      opioids (<240, 240--599, and > or =600 mg OME/48 hours) and of benzodiazepines
      (0, 1--59, and > or =60 mg parental midazolam equivalent/48 hours). Also, the
      survival of patients with haloperidol, hydroxyzine, and other sedative
      medications did not differ from those without. Furthermore, an addition of use of
      opioids and sedatives in the final 48 hours into the multiple regression model
      for survival prediction achieved no significant increase in predictability. In
      conclusion, opioids and sedatives used for symptom control in the last days are
      not associated with patient survival. They are safe and useful medications to
      palliate severe distress in the terminal stage of cancer when administered with a
      low initial dosage and adequate titration.

PMID- 11312043
TI  - Minority representation, prevalence of symptoms, and utilization of services in a
      large metropolitan hospice.
AB  - Minority access to and utilization of hospice services is gaining increasing
      attention in the field of health care delivery systems. This case study describes
      the 1997 ethnic and racial make-up of a large metropolitan hospice facility
      located in Arlington, Virginia and compares its composition with the regional
      community. Demographic data; aggregate physical and psychosocial problems;
      utilization of services; and admission, discharge, and mortality data were
      collected and summarized by race and ethnicity. The state provided 1997 regional
      mortality data by race and ethnicity. When hospice deaths were compared with
      regional deaths, the hospice provided service to 30% of Caucasians decedents, 20%
      of Asian decedents, 19% of Hispanic decedents, and 18% of African-American
      decedents. By using mortality data rather than census data, the discrepancy
      between minority and Caucasian populations is not as large as has been reported
      in previous research.

PMID- 11312044
TI  - Cancer pain management skills among medical students: the development of a Cancer
      Pain Objective Structured Clinical Examination.
AB  - Recent surveys suggest that most physicians have inadequate knowledge to assess
      and manage cancer pain; however, the important domain of clinical performance has
      not yet been clearly evaluated. The Objective Structured Clinical Examination
      (OSCE) has become a widely- used and accepted method to evaluate the clinical
      abilities of medical students. The purpose of this study was to develop and test
      a Cancer Pain OSCE for medical students evaluating their clinical competence in
      the area of cancer pain management. A four-component Cancer Pain OSCE was
      developed and presented to 34 third-year medical students during a sixteen-week
      combined medicine/surgery clerkship. The content of the objective criteria for
      each component of the OSCE was developed by a multidisciplinary group of pain
      experts. The OSCE was designed to assess the students' cancer pain management
      skills of pain history-taking, focused physical examination, analgesic management
      of cancer pain, and communication of opioid analgesia myths. Actual cancer
      survivors were used in the five-minute individual stations. The students were
      asked to complete a cancer pain history, physical examination, manage cancer pain
      using analgesics, and communicate with a family member regarding opioid myths.
      Clinical performance was evaluated using pre-defined checklists. Results showed
      the student's average performance for the history component was the highest of
      all four components of the examination. Out of 34 points possible on this
      clinical skills item, students on average (SD) scored 24.5 (5.2), or 72%. For the
      short-answer analgesic management component of the Cancer Pain OSCE, the overall
      score was 32%. Most students managed cancer pain with opioids, however, very few
      prescribed regular opioid use, and the use of adjuvant analgesics was uncommon.
      Student performance on the focused cancer pain physical examination was, in
      general, poor. On average students scored 61% on the musculoskeletal system, but
      only 31% on both the neurological and lymphathic examination. The overall percent
      score for the cancer pain OSCE was 48%. We conclude that the Cancer Pain OSCE is
      a useful performance-based tool to test individual skills in the essential
      components of cancer pain assessment and management. Of the four components of
      the Cancer Pain OSCE, medical students performed best on the cancer pain history
      and performed poorly on the cancer pain physical examination. Information gained
      from this study will provide a foundation on which future small-group medical
      student structured teaching will be based.

PMID- 11312045
TI  - Knowledge and perceived competence of home care nurses in pain management: a
      national survey.
AB  - This national mail survey assessed pain-related knowledge and subjective
      competence of a random sample of home care nurses across the United States. Other
      study objectives were to examine the relationship between nurse characteristics,
      knowledge and perceived competence, and assess continuing education practices. On
      average, the 1236 nurses scored only 56% of the items correctly, demonstrating
      stronger knowledge in pain assessment than treatment. Respondents reported most
      confidence in patient and family communication, discussion of advance directives
      and pain assessment. The lowest competence was reported in sophisticated pain
      treatment techniques. The relationship between knowledge and subjective
      competence was found to be highly significant. Sixty-three percent of the sample
      displayed a realistic assessment of their pain management knowledge, while 37%
      under- or overestimated what they knew. It is challenging to engage the latter
      group who overestimate their competence but score low on pain management
      knowledge. Educational strategies need to differentiate these two groups and
      target the audience appropriately.

PMID- 11312046
TI  - Nurses' knowledge of pain in the elderly.
AB  - The purpose of this study was to investigate nurses' knowledge of pain and pain
      management with respect to elderly persons. Registered nurses at several general
      hospitals and nursing homes were surveyed by questionnaire concerning their
      knowledge of pain management in the elderly. The findings indicated a significant
      knowledge deficit in this area. There were also significant differences in
      knowledge levels between general hospital nurses and those working in nursing
      homes. We conclude that more education about pain management in elderly patients
      is needed for nurses. This deficit needs to be addressed in both undergraduate
      nursing programs and hospital in-service courses. Presently, the majority of
      patients entering hospitals are aged 65 years and over. Hence, nurses in all
      areas of care, not just specifically those working in aged care facilities, need
      a sound knowledge of pain management of the elderly to facilitate compassionate
      and effective nursing care.

PMID- 11312047
TI  - Dyspnea, anxiety, body consciousness, and quality of life in patients with lung
      cancer.
AB  - Dyspnea is a common symptom of lung cancer that can impact patient physical,
      social, and psychological well-being. Study goals were to evaluate quality of
      life (QOL) and dyspnea in patients with lung cancer and the relationships between
      QOL, dyspnea, trait anxiety, and body consciousness. Sociodemographic and cancer
      related variables (stage, cell type, performance status) were evaluated. One
      hundred twenty outpatients with stage I-IV lung cancer participated in the study.
      Patients completed 5 questionnaires assessing QOL, dyspnea, trait anxiety, body
      consciousness, and pain. Eighty-seven percent of study participants experienced
      dyspnea. Patients with high dyspnea scores had lower QOL (P = 0.04). Dyspnea was
      worse in men than in women (P = 0.02), and there was a trend towards older
      patients reporting more severe dyspnea than younger patients (P = 0.06). There
      was no difference in dyspnea based on cancer stage, cell type, or performance
      status. Pain and anxiety scores were higher in patients with high dyspnea (P =
      0.02, P = 0.03). Dyspnea was more severe in patients taking opioid analgesics
      when compared to non-opioids or no pain medications (P = 0.03). No significant
      association was found between dyspnea, anxiety, and private body consciousness.

PMID- 11312048
TI  - Efficacy of peripheral morphine analgesia in inflamed, non-inflamed and
      perineural tissue of dental surgery patients.
AB  - In a clinical model of dental pain, the analgesic efficacy of local morphine
      treatment was examined under three different conditions. Patients undergoing
      dental surgery were randomly assigned to an injection of local anesthetic
      (articaine) plus 1 mg morphine either into inflamed (n = 14; trial 1) or non
      inflamed (n = 24; trial 2) submucous tissue or perineurally n = 19; trial 3).
      Patients in the control group for each condition (n = 13, trial 1; n = 26, trial
      2; n = 16, trial 3) received articaine plus saline. Postoperative pain intensity
      was assessed by the visual analog scale (VAS) and numeric rating scale (NRS) at
      0, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h. In addition, patients recorded the
      occurrence of side effects and the supplemental consumption of diclofenac.
      Immediately after the operation, pain scores were reduced to a similar extent in
      all groups, most likely due to the local anesthetic effect. Thereafter, pain
      scores and supplemental consumption of diclofenac were significantly lower in
      patients receiving 1 mg morphine into inflamed submucous tissue than in the
      control group for up to 24 h. Patients receiving 1 mg morphine into non-inflamed
      tissue or perineurally did not show any further reduction in pain scores compared
      to each control group. Our results show in patients undergoing dental surgery
      that injection of 1 mg of morphine into inflamed tissue results in significant
      and prolonged postoperative analgesia, whereas administration into non-inflamed
      tissue or perineurally is not effective. Thus, consistent with experimental
      studies, the requirement of an inflammatory process for the occurrence of
      peripheral opioid effects is also found in the clinical setting.

PMID- 11312049
TI  - Opioid poorly-responsive cancer pain. Part 3. Clinical strategies to improve
      opioid responsiveness.
AB  - Some pain syndromes may be difficult to treat due to a poor response to opioids.
      This situation demands a range of alternative measures, including the use of
      adjuvant drugs with independent effects, such as antidepressants, sodium channel
      blocking agents, steroids and anti-inflammatory drugs (NSAIDs); drugs that reduce
      opioid side effects; and drugs that enhance analgesia produced by opioids, such
      as N-methyl-D-aspartate (NMDA) antagonists, calcium channel antagonists, and
      clonidine. Other approaches, including opioid trials, neural blockade when
      necessary, and psychological interventions, also may be useful.

PMID- 11312050
TI  - Ethics rounds. A letter to friends.

PMID- 11312051
TI  - Ethics rounds. Words unspoken.

PMID- 11312052
TI  - Ethics rounds. Living fully while dying.

PMID- 11312053
TI  - Distribution of adrenomedullin-like immunoreactivity in the central nervous
      system of the frog.
AB  - Adrenomedullin (AM) is a recently discovered peptide widely distributed in the
      mammalian brain. By using an antiserum specific for human AM, we have analyzed
      the localization of AM-like immunoreactivity in the brain and spinal cord of the
      anuran amphibian Rana perezi. Cell bodies immunoreactive (AMi) for AM were
      located in the dorsal, lateral and medial pallial regions, diagonal band of
      Broca, medial septum, and above and rostral to the anterior commissure. A large
      population of AMi neurons was located in the anterior preoptic area,
      suprachiasmatic nucleus and in the infundibular hypothalamus. The processes of
      these latter cells are part of the hypothalamo-hypophysial pathway to the neural
      and intermediate lobes. Labeled cells were observed in the pretectal region,
      posterior tubercle and the mesencephalic anteroventral tegmental nucleus.
      Strikingly, Purkinje cells in the cerebellum also showed AM immunoreactivity,
      albeit not all of these cells were equally stained. Additional cells were located
      in the parabrachial region, principal trigeminal sensory nucleus, reticular
      nuclei medius and inferior, and the intermediolateral gray of the spinal cord.
      Immunolabeled fibers were widespread throughout the brain and spinal cord of the
      frog. They were particularly abundant in the medial amygdala, hypothalamus,
      mesencephalic tectum, periventricular gray and spinal cord. The distribution
      pattern of AM-like immunoreactivity in the brain of the frog is very selective
      and does not correspond with the pattern observed for any other transmitter or
      neuroactive molecule. The wide distribution of this peptide strongly suggests
      that it may play a significant role in the multiple neuronal functions in the
      amphibian brain.

PMID- 11312054
TI  - Alterations in neuropeptide expression in lumbosacral bladder pathways following
      chronic cystitis.
AB  - These studies examined changes in the expression of calcitonin gene-related
      peptide (CGRP) and substance P (SP) in lumbosacral (L6-S1) micturition reflex
      pathways, following chronic cystitis induced by cyclophosphamide (CYP). In
      control Wistar rats, CGRP- or SP-immunoreactivity (IR) was expressed in fibers in
      the superficial dorsal horn in all segmental levels examined (L4-S1). Bladder
      afferent cells in the dorsal root ganglia (DRG; L6, S1) from control animals also
      exhibited CGRP- (41-55%) or SP-IR (2-3%). Following chronic, CYP-induced
      cystitis, CGRP- and SP-IR were dramatically increased in spinal segments and DRG
      (L6, S1) involved in micturition reflexes. The density of CGRP- and SP-IR was
      increased in the superficial laminae (I-II) of the L6 and S1 spinal segments. No
      changes in CGRP- or SP-IR were observed in the L4-L5 segments. Staining was also
      dramatically increased in a fiber bundle extending ventrally from Lissauer's
      tract in lamina I along the lateral edge of the DH to the sacral parasympathetic
      nucleus in the L6-S1 spinal segments. Following chronic cystitis, CGRP- and SP-IR
      in cells in the L6 and S1 DRG significantly (P< or =0.05) increased and the
      percentage of bladder afferent cells expressing CGRP- (76%) or SP-IR (11-18%)
      also significantly (P< or =0.001) increased. No changes were observed in the L4
      L5 DRG. These studies suggest that the neuropeptides, CGRP and SP, may play a
      role in urinary bladder afferent pathways, following chronic urinary bladder
      inflammation. Changes in CGRP or SP expression following cystitis may contribute
      to the altered visceral sensation (allodynia) and/or urinary bladder
      hyperreflexia in the clinical syndrome, interstitial cystitis.

PMID- 11312055
TI  - Glycogen phosphorylase reactivity in the amygdala and bed nucleus of the stria
      terminalis.
AB  - The present study examines the reactivity of the glial metabolic enzyme, glycogen
      phosphorylase, within the amygdala and bed nucleus of the stria terminalis.
      Reactivity for phosphorylase a, the active form of glycogen phosphorylase, was
      higher in all parts of the medial amygdaloid nucleus, in the medial division of
      the central amygdaloid nucleus, in the anterior amygdaloid area and in the bed
      nucleus of stria terminalis than in all parts of the lateral amygdaloid nucleus,
      the anterior cortical amygdaloid nucleus, the posteromedial and posterolateral
      cortical amygdaloid nuclei, the intercalated nucleus of the amygdala, main part
      and the intercalated nuclei. A greater degree of phosphorylase a reactivity was
      also observed in the basolateral amygdaloid nucleus, anterior and posterior
      parts, and in the basomedial amygdaloid nucleus, anterior part, while other parts
      of these nuclei were less reactive. Reactivity attributed to total glycogen
      phosphorylase enzyme, phosphorylase a+phosphorylase b activated by AMP, was
      higher and homogeneous across the amygdala. Phosphorylase a patterns are likely
      to reflect differences in the contribution of glycogenolysis to the metabolic
      support of cells in the amygdala and bed nucleus of the stria terminalis.
      Possible relationships to local neuronal activity and to differences in
      glycogenolytic neuromodulatory input are discussed.

PMID- 11312056
TI  - Effect of food manipulation on the neuropeptide Y neuronal system in the
      diencephalon of ewes.
AB  - The expression of neuropeptide Y (NPY), which is involved in the neuromodulatory
      function associated with animal nutrition, growth and reproduction, depends on
      the nutritional status. However, the roles of individual components of food are
      not fully recognised. In this study, we evaluated the effects of dietary protein
      levels on the diencephalic population of NPY neurones. Female lambs were fed two
      diets equilibrated energetically but containing 8% protein in restricted diet or
      18% protein in elevated diet, for 15 weeks starting with 6 months of age, during
      the first breeding period. Then, brain tissues were collected, fixed and used for
      the immunohistochemical localisation of NPY. Detection of NPY in diencephalon
      sections was followed by the image analysis and expressed as the percent area
      stained and optical density of immunostaining. Two distinct populations of the
      immunoreactive NPY perikarya were found, one in the infundibular nucleus; and the
      other in areas of diencephalon adjacent to the rostral hypothalamus. Long-term
      feeding the protein restricted diet caused a prominent expression of the
      immunoreactive material solely in the hypothalamic NPY neurones, particularly in
      those located in the entire periventricular area and in the infundibular nucleus.
      Both, percent area exhibiting positive staining and the density of immunoreactive
      NPY measured in the periventricular subdivision of the paraventricular nucleus
      were significantly higher (P<0.05) in sheep fed restricted diet, than in sheep
      fed on elevated diet. This study describes the distribution of NPY neurones in
      the sheep diencephalon, and shows the relationships between the expression of
      hypothalamic population of NPY neurones and the level of protein feeding.

PMID- 11312057
TI  - Depletion of substance P, neurokinin A and calcitonin gene-related peptide from
      the contralateral and ipsilateral caudal trigeminal nucleus following unilateral
      electrical stimulation of the trigeminal ganglion; a possible neurophysiological
      and neuroanatomical link to generalized head pain.
AB  - Primary trigeminal neurons of the trigeminal ganglion (TG) innervate major parts
      of the face and head, including the dura. Electrical stimulation of the TG at
      specific parameters, can activate its nociceptive neurons and may serve as an
      experimental pain model. Markowitz [J. Neurosci. 7 (1987) 4129] reported that
      electrical stimulation of the trigeminal ganglion (TG) causes extravasation of
      plasma proteins from venules of the trigeminally innervated domain possibly due
      to the release of vasoactive substances. Neurogenic inflammation (vasodilatation,
      plasma protein extravasation, release of vasoactive peptides) in dura may serve
      as one of the possible pathomechanisms underlying vascular head pain [Moskowitz,
      Ann. Neurol. 16 (1984) 157]. We performed a unilateral electrical stimulation
      (7.5 Hz, 5 ms, 0.8-1.4 mA for 5 min) of the TG in rat, to induce a neurogenic
      inflammation in the peripheral trigeminal domain including the dura, looking for
      calcitonin gene related peptide (CGRP), substance P (SP) and neurokinin A (NKA)
      immunoreactivity (IR) in the caudal trigeminal nucleus (CTN) into which massive
      central trigeminal processes terminate. Here, we show patchy depletion(s) of CGRP
      , SP- and NKA-IRs in the contralateral CTN of the rat in addition to their
      ipsilateral depletion. Such depletion is due to the release of these
      neuropeptides in the CTN leading to the activation of bilateral trigeminal
      nociceptive pathway. These data afford the possibility that under specific
      frequencies (which may roughly correlate to the intensity of the painful
      stimulus) and/or specific intensities (may correlate to specific areas of the
      peripheral trigeminal domain) of stimulation, activation of one side of the TG
      may activate bilateral trigeminal nociceptive pathway leading to the perception
      of an ill localized/generalized pain or headache rather than a unilateral one.

PMID- 11312058
TI  - New central projections of neuropeptide FF: colateral branching pathways in the
      brainstem and hypothalamus in the rat.
AB  - Neuropeptide FF (NPFF), a morphine modulatory peptide, has been identified within
      discrete autonomic regions in the brainstem and hypothalamus. Triple fluorescence
      labelling was employed to identify collateral branching projections of NPFF
      neurons located within the nucleus tractus solitarius (NTS) and in the region of
      the hypothalamus between the dorsomedial and ventromedial hypothalamus.
      Injections of two retrograde tracers, rhodamine- and fluorescein-labelled latex
      microspheres into the pontine parabrachial nucleus (PBN) and the ventrolateral
      medulla resulted in labelling of NPFF neurons in the NTS that contained one
      (double-labelled) or both (triple-labelled) tracers. Within the NTS, most double-
      and triple-labelled NPFF neurons were localized at the level of the area postrema
      or just rostral to it and within the medial and dorsomedial subdivisions of the
      nucleus. Injections of tracers into the PBN and hypothalamic paraventricular
      nucleus revealed double- and triple-labelled NPFF neurons, a majority of which
      were located in a zone between the dorsomedial and ventromedial hypothalamus.
      These results indicate that NPFF neurons in the brainstem and hypothalamus may
      simultaneously transmit signals to their target nuclei in the brainstem and
      forebrain. This coordinated signalling may lead to synchronized responses of NPFF
      target sites and provide insights into the role of this peptide in cardiovascular
      and nociceptive responses.

PMID- 11312059
TI  - Nitric oxide synthase neurons in the rodent spinal cord: distribution, relation
      to Substance P fibers, and effects of dorsal rhizotomy.
AB  - The indirect immunofluorescent method was employed to investigate the
      distribution of neuronal nitric oxide synthase-like immunoreactivity(nNOS-LI) in
      the spinal cord of the golden hamster and to compare it to data obtained from
      rats. Immunoreactive neurons were found throughout the cervico-sacral extent in
      the dorsal horn (mainly in laminae I-III) and in the preganglionic autonomic
      regions, i.e., the sympathetic intermediolateral nucleus (IML), lateral funicle
      (LF), intercalated region (IC), the area surrounding the central canal (CA), and
      the sacral preganglionic parasympathetic cell group. While the distribution of
      immunoreactive cells was generally similar in both species, some differences were
      observed. For example in the hamster LF, a higher percentage of stained neurons
      was seen than in the IML, while the situation was rather inverse in the rat. In
      order to study the coincidence of nNOS-LI in the population of preganglionic
      sympathetic neurons (PSN) that innervate the superior cervical ganglion (SCG),
      these were identified by retrograde axonal transport of fluoro-gold (FG)
      following unilateral injection into the SCG. PSN were localized ipsilateral to
      the injection site mainly in the IML and LF of spinal segments C7-Th4. The
      portion of double-labeled neurons of the IML were lower in hamster (17% in C7,
      34% in C8) of FG-labeled cells) than in rat (47% in C8, 77% in Th2), while in the
      LF of segments C8-Th2 in both species the majority of FG-neurons contained nNOS.
      While only very few double-labeled neurons were detected in the IC in hamster and
      rat, a striking difference was observed in the CA, where no double-labeled
      neurons were found in hamster, but up to 50% in rat. Double immunofluorescence
      detection of nNOS and substance P (SP) showed that in both the autonomic regions
      and the dorsal horn, SP-LI fibers and puncta were present in close spatial
      relationship to nNOS-LI cell bodies. These results were basically identical in
      the hamster and rat. Unilateral transection of the dorsal roots of segments C6
      Th2 in rats resulted in a clear reduction of SP-LI structures in the dorsal horn
      5 days after rhizotomy, but not in the autonomic regions. Compared to the
      unlesioned side, the numbers of nNOS-LI neurons in the superficial laminae of the
      dorsal horn were reduced to 32-46% in the lesioned segments, and to 53% and 87%,
      respectively, in the two segments cranial to the rhizotomized segments but
      remained unchanged caudally to the lesion. Numbers of nNOS-LI cell bodies in the
      autonomic regions were not altered following dorsal root transection. The present
      study provides data on the widespread distribution of nNOS in the spinal cord of
      golden hamster and describes the partial coincidence of the enzyme in PSN. The
      effects of dorsal rhizotomy on nNOS-LI neurons in the dorsal horn reveal that
      primary-afferent fibers provide a stimulatory influence on neurons of the dorsal
      horn to generate the gaseous neuroactive substance, nitric oxide.

PMID- 11312060
TI  - John M. Kinney International Awards. Reflections: the development of my interest
      in muscle wasting, preservation, and restoration.

PMID- 11312061
TI  - John M. Kinney International Awards. Looking back: a human reason for studying
      the effects of glutamine in patients with AIDS.

PMID- 11312062
TI  - John M. Kinney International Awards. A summary of our work: effects of
      intravenous omega-6 and omega-3 fat emulsions on nitrogen retention and protein
      kinetics in burned rats.

PMID- 11312063
TI  - Magnesium absorption using stable isotope tracers in healthy children and
      children treated for leukemia.
AB  - Intestinal magnesium (Mg) absorption was measured in six healthy children
      (control) and in four children treated for acute lymphoblastic leukemia with the
      single-isotope fecal recovery technique (SIFRT). The objective of this study was
      to determine Mg absorption in young children with acute lymphoblastic leukemia
      using stable isotope tracers. Fractional and absolute absorption levels
      determined by SIFRT were not significantly different between children with acute
      lymphoblastic leukemia (fractional absorption: 58.3 +/- 10.6% [mean +/- SEM],
      absolute absorption: 3.66 +/- 0.71 mg x kg(-1) x d(-1), [0.15 +/- 0.03 mmol x kg(
      1) x d(-1)]) and control children (fractional absorption: 61.4 +/- 7.5%, absolute
      absorption: 5.69 +/- 0.85 mg x kg(-1) x d(-1), [0.23 +/- 0.03 mmol x kg(-1) x d(
      1)]). Average Mg absorption in young children (aged 3--8 y) was 60.2 +/- 5.8%.
      This study describes the first application of the SIFRT to assess Mg absorption
      in young children and illustrates the feasibility of the SIFRT in this age group
      to obtain more accurate information on Mg absorption.

PMID- 11312064
TI  - Low-frequency physical activity insufficient for aerobic conditioning is
      associated with lower body fat than sedentary conditions.
AB  - We aimed to show the relationships between reported physical activity, fitness
      level, and body composition in healthy adult office-working Kuwaiti males (n =
      45). Reported level of physical activity (group 0 = no routine exercise, n = 10;
      group 1 = routine exercise once per wk, n = 19; group 2 = routine exercise two or
      more times per wk, n = 16) was determined from recall questionnaires. Aerobic
      fitness levels were assessed from resting exercise heart rates and measurement of
      maximal oxygen uptake (treadmill exercise, Bruce protocol). Body composition was
      estimated from measurements of body weight, body height, and seven skin-folds.
      None of the subjects reported dieting to reduce or maintain their body weight.
      Despite minimal and not statistically significant differences in resting heart
      rates, VO(2)max, VO(2)max/kg body weight, and VO(2)max/kg lean body mass, the
      sedentary group (group 0) had a much higher (12--14 kg) average body weight,
      higher (12--13 kg) body fat, and thicker skin folds than the more physically
      active groups 1 and 2. Groups 1 and 2 did not differ significantly from each
      other with regard to fitness and body composition parameters. Thus, routine
      physical activities insufficient to result in aerobic conditioning were found to
      be associated with lower body weight and lower body fat compared to those present
      in subjects reporting the total absence of any routine physical activity. These
      data are consistent with the hypothesis that even mild levels of routine physical
      activity are associated with levels of energy turnover that allow less intense
      and/or frequent periods of positive energy balance, resulting in maintenance of
      lower body fat than in totally sedentary people. Frequency of participation in
      routine physical activities may also reflect the level of non-exercise related
      physical activities and thus relate to the ability to minimize weight gain.

PMID- 11312065
TI  - Impaired pancreatic secretion in severely malnourished patients is a consequence
      of primary pancreatic dysfunction.
AB  - Severe undernutrition has been associated with reduced secretions of gastric acid
      and pancreatic enzymes. This may be the result of an impaired gut mucosal
      response to food and primary gastric parietal and pancreatic acinar cell
      secretory dysfunction as a consequence of the poor nutritional state. To
      investigate the relative contributions of these factors, severely undernourished
      patients underwent enteral-meal-stimulated (ES; n = 7) or intravenous hormone
      (pentagastrin and cholecystokinin-8)-stimulated (HS; n = 12) gastric acid and
      pancreatic enzyme secretion before and after a period of nutritional support.
      Results were evaluated in comparison with normal healthy control subjects (ES =
      7, HS = 10). In the control subjects, enteral-meal and cholecystokinin-8
      stimulation resulted in similar outputs of the pancreatic enzymes amylase (2213
      versus 2305 U/h), lipase (84.93 versus 118.6 U/h), and trypsin (498.9 versus
      341.4 U/h), whereas acid output was significantly lower in the ES group (10.90
      versus 25.53 mEq/h; P < 0.01). Compared with controls, malnourished groups had
      significantly reduced secretions of amylase (ES = 870.1 U/h, HS = 686.5 U/h; P <
      0.02), lipase (ES = 30.68 U/h, HS = 25.96 U/h; P < 0.02), and trypsin (ES = 175.6
      U/h, HS = 109.3 U/h; P < 0.01). The response to enteral-meal or CCK-8 stimulation
      was comparable. Gastric acid was similarly reduced in the undernourished patients
      (ES = 4.39 mEq/h, HS = 5.04 mEq/h; P < 0.01). After refeeding, secretion of
      amylase (ES = 2351 U/h, HS = 2228 U/h) and lipase (ES = 58.83 U/h, HS = 84.91
      U/h) improved to levels not significantly different from controls, whereas
      trypsin (ES = 226.4 U/h, HS = 213.1 U/h; P < 0.03) and acid secretion (ES = 3.52
      mEq/h, HS = 11.85 mEq/h; P < 0.01) remained significantly impaired. Severe
      undernutrition was associated with primary gastric parietal and pancreatic acinar
      cell dysfunction, which, at least in the case of pancreatic enzymes, appeared to
      be the determining factor controlling secretion in these patients.

PMID- 11312066
TI  - Prevalence of type 2 diabetes and obesity in rural Mapuche population from Chile.
AB  - The aim of this study was to estimate the prevalence of Type 2 diabetes, impaired
      glucose tolerance (IGT), and obesity in the Mapuche natives from rural areas in
      Chile. This cross-sectional study involved men (n = 95) and women (n = 224) older
      than 20 y from an aboriginal ethnic group (Mapuches), residing in rural
      communities from the south of Chile. Prevalence of Type 2 diabetes and IGT was
      calculated according to the World Health Organization criteria. Data on age,
      degree of ancestral purity, obesity, and hypertension were also obtained. The
      prevalence of Type 2 diabetes in rural Mapuche natives was estimated as 3.2% (95%
      CI: 0.7--9.0) in men and 4.5% (95% CI: 2.2--8.1) in women. The overall prevalence
      of obesity was 56.1% (95% CI: 50.5--61.6): 40.0% (95% CI: 30.1--40.8) in men and
      62.9% (95% CI: 56.3--69.3) in women (P value < 0.001). These data suggest that
      the prevalence of obesity and Type 2 diabetes has been increasing during recent
      years in the Mapuche communities. The prevalence estimated in this study is
      higher than that reported 15 y ago. This suggests an important role of lifestyle
      changes as a possible explanation for epidemiologic transition.

PMID- 11312067
TI  - Whole-body protein turnover in malnourished patients with child class B and C
      cirrhosis on diets low to high in protein energy.
AB  - The purpose of this study was to determine the rate of whole-body protein
      turnover in moderately and severely alcoholic, malnourished, cirrhotic patients
      fed with different amounts of protein or energy. Six male patients (Child classes
      B and C) and four age- and sex-matched healthy control subjects were studied for
      18 d in fasting and feeding states; a single oral dose of [(15)N]glycine was used
      as a tracer and urinary ammonia was the end product. The kinetic study showed
      that patients had higher protein catabolism while fasting (patients: 3.14 +/- 1.2
      g of lean body mass/9 h; controls: 1.8 +/- 0.3 g of lean body mass/9 h; P <
      0.02). Although not statistically significant, protein catabolism (grams of lean
      body mass/9 h) was lower with the hyperproteic/hyperenergetic diet when compared
      with fasting. Nitrogen retention was consistent with the lower protein-catabolism
      rate; a statistically significant increase in nitrogen balance was observed when
      patients were fed with the hyperproteic/hyperenergetic diet compared with fasting
      (4.3 +/- 3.2 g of nitrogen/d and -2.2 +/- 1.9 g of nitrogen/d, respectively; P <
      0.01). These data indicate that Child class B and C cirrhotic patients are
      hypercatabolic and that long-term nutritional intervention with a
      hyperproteic/hyperenergetic diet is likely needed to improve their clinical and
      nutritional status.

PMID- 11312068
TI  - The effects of bovine colostrum supplementation on body composition and exercise
      performance in active men and women.
AB  - The purpose of this study was to determine the effect of 8 wk of bovine colostrum
      supplementation on body composition and exercise performance in active men and
      women. Subjects were randomly assigned to a placebo (whey protein) and colostrum
      group (20 g/d in powder form). Each subject participated in aerobic and heavy
      resistance training at least three times per wk. Body composition was assessed
      via dual x-ray absorptiometry analysis. Treadmill time to exhaustion, one
      repetition maximum strength (bench press), and the total number of repetitions
      performed during one set to exhaustion at a submaximal load for the bench press
      (50% and 100% of body weight for women and men, respectively) were ascertained.
      The whey protein group experienced a significant increase (P < 0.05) in body
      weight (mean increase of 2.11 kg), whereas the colostrum group experienced a
      significant (P < 0.05) increase in bone-free lean body mass (mean increase of
      1.49 kg). There were no changes in any of the other parameters measured. Thus,
      supplementation with bovine colostrum (20 g/d) in combination with exercise
      training for 8 wk may increase bone-free lean body mass in active men and women.

PMID- 11312069
TI  - Single prediction equation for bioelectrical impedance analysis in adults aged 20
      -94 years.
AB  - Existing equations for bioelectrical impedance analysis (BIA) are of limited use
      when subjects age or become overweight because these equations were developed in
      young, normal-weight subjects and are not valid in elderly or overweight people.
      The purpose of this study was to validate a single BIA equation in healthy white
      subjects aged 22--94 y with a body mass index between 17.0 and 33.8 kg/m(2).
      Healthy subjects (202 men and 141 women) aged 20--94 y were measured by two
      methods: fat-free mass (FFM) was measured by dual-energy x-ray absorptiometry
      (Hologic QDR-4500) and by a bioelectrical impedance analyzer (Xitron 4000B).
      Validity of BIA was assessed by double cross validation. Because correlations
      were high (r = 0.986--0.987) and prediction errors low, a single equation was
      developed using all subjects, as follows: FFM = -4.104 + (0.518 x
      height(2)/resistance) + (0.231 x weight) + (0.130 x reactance) + (4.229 x sex:
      men = 1, women = 0). FFM predicted with dual-energy x-ray absorptiometry was 54.0
      +/- 10.7 kg. BIA-predicted FFM was 54.0 +/- 10.5 kg (r = 0.986, standard error of
      the estimate = 1.72 kg, technical error = 1.74 kg). In conclusion, the new Geneva
      BIA equation was valid for prediction of FFM in healthy adults aged 22--94 y with
      body mass indexes between 17.0 and 33.8 kg/m(2). Inclusion of reactance in the
      single prediction equation appeared to be essential for use of BIA equations in
      populations with large variations in age or body mass.

PMID- 11312070
TI  - Small-intestine absorption during continuous intraduodenal infusion of nutrients
      in dogs.
AB  - Motility and exocrine and endocrine secretions of the gastrointestinal tract are
      modified during postprandial periods. Experimental evidence suggests that
      nutrients stimulate small-intestine absorption, but the mechanisms involved are
      uncertain. Further, the effects of mixing nutrients with different
      physicochemical compositions on absorption and motility are not completely
      elucidated. With the use of a canine model, we investigated the effects of a
      mixture of different lipids and proteins on small-intestine motility and
      absorption. Two cannulae, one in the proximal duodenum and one in the distal
      ileum, were implanted in the dogs. Absorption of a continuous duodenal infusion
      of eight test mixtures consisting of long- and medium-chain fatty-acid
      triacylglycerols, soy protein and its hydrolysate, casein and its hydrolysate,
      and variable amounts of glucose, and glucose polymer were analyzed by measuring
      the volume, concentration, and total amount of triacylglycerols, nitrogen, and
      glucose recovered from the ileal cannula. Significant differences in absorption
      were observed across test mixtures. Significantly lower absorption of H(2)O and
      nutrients was observed with test mixtures prepared with medium-chain fatty-acid
      triacylglycerols and soy protein compared with test mixtures prepared with corn
      oil, casein, and hydrolysates of both proteins. We concluded that the
      physicochemical characteristics of nutrients in elemental diets continuously
      infused into the duodenum are important for determining small-intestine
      absorption.

PMID- 11312071
TI  - Where do all the minerals go? Finding the causes of long-term mineral deficiency
      in children with serious illnesses.

PMID- 11312072
TI  - The brain-lipid-heart connection.

PMID- 11312073
TI  - Malnutrition in the critically ill.

PMID- 11312074
TI  - Role of the upper gastrointestinal tract in regulation of human feeding.

PMID- 11312075
TI  - How genes control real world intake: palatability--intake relationships.

PMID- 11312076
TI  - Lactobacilli for the management of Helicobacter pylori.

PMID- 11312077
TI  - Sports nutrition: what is it?

PMID- 11312078
TI  - Balancing the quality cycle: tackling the measurement-improvement gap in health
      care. Part II.

PMID- 11312079
TI  - Alternative and complementary nutritional therapies in cancer prevention and
      treatment: implications in clinical practice.

PMID- 11312080
TI  - Organizational and management issues: a multidisciplinary approach.

PMID- 11312081
TI  - Nosocomial and iatrogenic infections.

PMID- 11312083
TI  - Free papers: varia.

PMID- 11312082
TI  - Free papers on proctology and phlebology.

PMID- 11312084
TI  - Free papers on pain and follow up.

PMID- 11312085
TI  - Medicolegal implications.

PMID- 11312087
TI  - Controversies in ambulatory surgery.

PMID- 11312086
TI  - Interventional radiology.

PMID- 11312088
TI  - Recovery and street versus home fitness criteria.

PMID- 11312089
TI  - Free papers on quality control in ambulatory surgery - Session 7a.

PMID- 11312090
TI  - Free papers on preoperative managament.

PMID- 11312091
TI  - Free Papers on Nursing Issues - Session 8a.

PMID- 11312092
TI  - Free papers on pediatric ambulatory surgery.

PMID- 11312093
TI  - Free papers on hernia surgery.

PMID- 11312094
TI  - Free papers of Session 10b.

PMID- 11312095
TI  - Poster session.

PMID- 11312096
TI  - Teaching and training in ambulatory surgery, patient education.

PMID- 11312097
TI  - Should ASC be designed by doctors or architects.

PMID- 11312099
TI  - Abstracts of video session.

PMID- 11312098
TI  - Poster session.

PMID- 11312101
TI  - Nitric oxide modulates the angiogenic phenotype of middle-T transformed
      endothelial cells.
AB  - The role of nitric oxide (NO) in the induction of angiogenesis was evaluated in a
      murine heart endothelioma cell line (H.end.FB) carrying the mT oncogene. Two
      clonal derivatives of H.end.FB, H80 and H73, exhibiting different NO synthase
      (NOS) activities were selected and used in the study. The relationship among NOS
      activity and tumor cell behaviour (growth, and angiogenic capacity) and the
      molecular control of gene expression were investigated. H.end.FB and H80 on one
      side and H73 on the other side exhibited the highest and lowest NOS activity,
      respectively. Cell growth was inversely correlated to the amount of NO produced
      by the cell lines. Conversely, in the avascular rabbit cornea assay, H.end.FB and
      H80 cells were strongly angiogenic, while H73 were poorly angiogenic, indicating
      that the ability of the cells to induce neovascularization was associated with
      the extent of NO produced. Consistently, systemic administration to rabbits of
      the NOS inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME) significantly
      reduced the angiogenicity of H.end.FB cells. RT-PCR evidenced that H.end.FB
      expressed mRNA for TGF-beta1 and all VEGF isoforms, VEGF165 being predominantly
      expressed. NOS inhibition reduced the basal expression of VEGF isoforms, while it
      markedly potentiated TGF-beta1 expression. These results indicate that the
      endogenous production of NO in tumor cells can serve as an autocrine/paracrine
      signalling mechanism of progression, by controlling angiogenic factor/modulator
      expression.

PMID- 11312102
TI  - Signaling properties of VEGF receptor-1 and -2 homo- and heterodimers.
AB  - Vascular endothelial growth factor (VEGF-A) exerts its effects through receptor
      tyrosine kinases VEGF receptor-1 (VEGFR-1) and VEGFR-2, which are expressed on
      most endothelial cell types in vitro and in vivo. We have examined VEGF-A-induced
      signal transduction in porcine aortic endothelial (PAE) cells individually
      expressing VEGFR-1 or VEGFR-2, and cells co-expressing both receptor types. We
      show that VEGF-A-stimulated PAE cells co-expressing VEGFR-1 and -2 contain
      receptor heterodimers. VEGF-A-stimulation of all three cell lines (expressing
      VEGFR-1, -2 and -1/2) resulted in signal transduction with different
      efficiencies. Thus, tyrosine phosphorylation of phospholipase Cgamma, and
      accumulation of inositol polyphosphates were efficiently transduced in the VEGFR
      1/2 cells whereas cells expressing VEGFR-1 responded poorly in these assays. In
      contrast, VEGF-A-induced activation of phosphoinositide 3-kinase and induction of
      Ca2+ fluxes were transduced well by VEGFR-1 and VEGFR-2 homo- and heterodimers.
      The pattern of Ca2+ fluxes was unique for each type of VEGF receptor dimer. Our
      data show that signal transduction induced by VEGF-A is transduced in distinct
      manners by homo- and heterodimers of VEGF receptors.

PMID- 11312103
TI  - Identification of tumour-induced changes in endothelial cell surface protein
      expression: an in vitro model.
AB  - The selective destruction of the supporting vasculature of tumours has been
      proposed as a means of therapy. Fundamental to this approach is the
      identification of suitable targets on tumour-endothelium. To detect proteins that
      may be up-regulated on the luminal (apical) surface of tumour-associated
      endothelium confluent endothelial cells were examined following incubation with
      tumour cell conditioned medium (TCM) from, or co-culture with, a range of breast
      carcinoma and small cell lung carcinoma (SCLC) cell lines. Exposed endothelial
      membrane proteins were labelled with sulpho-NHS-biotin and detected by enhanced
      chemiluminescence following two-dimensional polyacrylamide gel electrophoresis (2
      D PAGE) and western blotting. TCM induced varying levels of proliferative
      activity in endothelial cells; generally breast TCM contained greater mitogenic
      activity than SCLC TCM. Exposure of human breast and lung microvascular, and
      umbilical vein endothelial cells to soluble tumour cell factors from several
      breast cancer and SCLC cells lines produced similar changes in luminal protein
      profiles: Breast cancer cells and in particular the MDA-MB-231 cell line induced
      the most pronounced changes. The expression of six proteins was altered
      consistently on endothelial cells stimulated with soluble tumour cell factors.
      However, similar changes were observed following incubation with ECGS suggesting
      that they were related to endothelial cell proliferation per se. As these
      proteins were altered in breast and lung microvascular, and umbilical vein
      endothelial cells stimulated by a variety of breast cancer and SCLC cell lines
      they support the potentially broad applicability of anti-vascular approaches
      targeted at the endothelium.

PMID- 11312104
TI  - Vascular endothelial growth factor-A activates Ca2+ -activated K+ channels in
      human endothelial cells in culture.
AB  - Vascular endothelial growth factor-A (VEGF-A) is an endothelial-cell specific
      growth factor and leads to an increase in cytosolic free calcium ([Ca2+](i)) in
      endothelial cells. Ca2+ -activated K+ channels (KCa-channels) have been suggested
      to facilitate calcium influx by hyperpolarising the cell and thus increasing the
      electrochemical driving force for calcium influx. The patch-clamp technique was
      used to investigate the effect of VEGF-A on large conductance KCa-channels. The
      role of these channels in VEGF-induced proliferation (cell count, [3H]thymidine
      incorporation) was studied using the specific inhibitor iberiotoxin. VEGF-A
      strongly stimulated KCa-channel activity and led to a 14.2 +/- 4.8 fold (SEM, n =
      12) increase in activity after 8 min of VEGF-A stimulation. The VEGF-A-induced
      activation occurred in calcium-free solution as well (16.7+/-2.2 fold, SEM, n =
      5) whereas carboxyamidotriazole (CAI), an antiangiogenic drug which inhibits both
      Ca2+ influx and Ca2+ release from intracellular stores, completely blocked VEGF-A
      induced KCa channel activation. Specific inhibition of KCa channel activity with
      iberiotoxin did not inhibit proliferation of endothelial cells induced by VEGF-A
      and or basic fibroblast growth factor (bFGF). In conclusion, we show that VEGF-A
      activates KCa-channels in HUVEC. However, KCa channel activity is not involved in
      VEGF-A- or bFGF-induced endothelial-cell proliferation. Since hyperpolarization
      of endothelial cells secondary to KCa-channel activation is electrically
      transmitted to vascular smooth muscle cells, which relax in response to
      hyperpolarization, the VEGF-A-induced KCa channel activation might contribute to
      VEGF-A-induced vasorelaxation.

PMID- 11312105
TI  - Selective expression of erg isoforms in human endothelial cells.
AB  - Erg and Fli-1 are closely related members of the ets family of transcription
      factors. There are at least five human Erg isoforms (Erg-1, Erg-2, Erg
      3/p55(Erg), p49(Erg) and p38(Erg)) produced through differential mRNA splicing
      and alternative use of translational start codons. However, relatively little is
      known about the expression or function of these isoforms in vitro or their
      distribution in vivo. We used RT-PCR to screen a panel of primary and established
      human cell lines for erg and fli-1 consensus sequences. Whilst fli-1 was
      expressed in several human cell types, erg was detected mainly in endothelial
      cells. To identify which erg isoforms are expressed in endothelial cells we used
      RT-PCR, Northern blotting and 5'-RACE. Erg-3/p55(Erg) and p38(Erg)/p38(Erg)-like
      transcripts were detected in both microvascular and large vessel endothelial
      cells affinity-purified from different vascular beds. Moreover, these erg
      isoforms were present in both freshly isolated, and confluent endothelial cells
      following several passages in culture, indicating that endothelial erg expression
      in vitro may be broadly representative of that in vivo. The selective expression
      of the Erg-3/p55(Erg) and p38(Erg)/p38(Erg)-like isoforms in endothelial cells
      indicates their involvement in the regulation of endothelial-restricted genes.

PMID- 11312106
TI  - Endogenous angiogenesis inhibitors and their therapeutic implications.
AB  - A number of endogenous inhibitors targeting the tumor vasculature have recently
      been identified using in vitro and in vivo antiangiogenesis models. While many of
      these angiogenesis inhibitors display a broad spectrum of biological actions on
      several systems in the body, several inhibitors including angiostatin,
      endostatin, and serpin antithrombin seem to act specifically on the proliferating
      endothelial cell compartment of the newly formed blood vessels. The discovery of
      these specific endothelial inhibitors not only increases our understanding of the
      functions of these molecules in the regulation of physiological and pathological
      angiogenesis, but may also provide an important therapeutic strategy for the
      treatment of cancer and other angiogenesis dependent diseases, including diabetic
      retinopathy and chronic inflammations. Systemic administration of these
      angiogenesis inhibitors in animals significantly suppresses the growth of a
      variety of tumors and their metastases. However, their production as functional
      recombinant proteins has been proven to be difficult. In addition, high dosages
      of these inhibitors are required to suppress tumor growth in animal studies.
      Other disadvantages of the antiangiogenic protein therapy include repeated
      injections, prolonged treatment, transmission of toxins and infectious particles,
      and high cost for manufacturing large amounts of protein molecules. Thus,
      alternative strategies need to be developed in order to improve the clinical
      settings of antiangiogenic therapy. Developments of these strategies are ongoing
      and they include identification of more potent inhibitors, antiangiogenic gene
      therapy, improvement of protein/compound half-lives in the circulation, increase
      of their concentrations at the disease location, and combinatorial therapies with
      approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the
      above-mentioned disadvantages, a few inhibitors have entered into the early
      stages of clinical trials and they may bring new hopes for the treatment of
      cancer and other angiogenesis dependent diseases.

PMID- 11312107
TI  - Interactions between endothelial cells and HIV-1.
AB  - Endothelial cells (EC) participate in inflammatory and immune reactions by
      producing and responding to soluble mediators. Human immunodeficiency virus (HIV)
      1 profoundly alters the features of EC. In some anatomical districts, they are
      infected by the virus and may represent a relevant reservoir. During
      lymphomononuclear cell diapedesis, EC activate virus replication in crossing
      cells. Direct or indirect damage of EC is particularly relevant in central
      nervous system, where blood-brain barrier perturbation is pivotal in neuronal
      degeneration. The observed alterations of EC adhesive properties contribute in
      altered leukocyte traffic from blood to lymphoid organs and tissues and play a
      role in the onset of immune surveillance alteration. These alterations of EC
      functions are relevant for the general vasculopathy, which marks the acquired
      immunodeficiency syndrome, and in particular are instrumental in the pathogenesis
      of Kaposi's sarcoma. Here we discuss the biological and molecular activation of
      EC in HIV-1 infection that represents the basis to understand the pathogenesis of
      HIV-1 associated vascular diseases.

PMID- 11312108
TI  - The Ets family contains transcriptional activators and repressors involved in
      angiogenesis.
AB  - The Ets family contains a growing number of transcriptional activators and
      inhibitors, which activity is regulated by phosphorylation and protein-protein
      interactions. Among these factors, Ets1, Erg1 and Fli1 are expressed in
      endothelial cells during angiogenesis in normal and pathological development. The
      expression of these transcription factors is regulated by angiogenic factors in
      cultured endothelial cells, as well as by various stresses occurring during
      angiogenesis. Transfection experiments and transgenic mice analysis revealed that
      Ets family members are involved in the transcriptional regulation of endothelial
      specific genes such as those encoding Tie1 and -2, VEGFR1 and -2 and VE-Cadherin.
      In vitro studies plead for a role of Ets family members in endothelial cell
      adhesion, spreading and motility. Gene inactivation experiments show that Ets1 is
      dispensable for embryonic development. The phenotype of knocked-out embryos
      indicates that Tel is required for maintenance of the developing vascular network
      in the yolk sac. Altogether, we suggest that Ets family members act both
      positively and negatively during the different steps of the angiogenic process.
      The regulation of the initiation of gene transcription arises from the combined
      activity of different transcriptional regulators. Therefore very few
      transcription factors are specific for a physiological process, or a given cell
      type. The transcriptional network that regulates blood vessel formation involves
      transcription factors which are expressed in a variety of situations. The Lung
      Kruppel Like Factor (LKLF) which is required for blood vessel stabilisation
      during murine development is also expressed in the primitive vertebrae and in the
      lung of the adult (C.T. Kuo, M.L. Veselits, K.P. Barton, M.M. Lu, C. Clendenin,
      J.M. Leiden, The LKLF transcription factor is required for normal tunica media
      formation and blood vessel stabilisation during murine embryogenesis, Genes Dev.
      11 (22) (1997) 2996-3006). Scl/Tal1 which is essential for angiogenic remodelling
      of the yolk sac capillary network (J.E. Visvader, Y. Fujiwara, S.H. Orkin,
      Unsuspected role for the T-cell leukemia protein SCL/tal-1 in vascular
      development, Genes Dev. 12 (4) (1998) 473-479), is involved in blood cell
      development and is also expressed in the developing brain. The EPAS transcription
      factor which was thought to be endothelial cell specific in the mouse embryo (H.
      Tian, S.L. McKnight, D.W. Russell, Endothelial PAS domain protein 1 (EPAS1), a
      transcription factor selectively expressed in endothelial cells, Genes Dev. 11
      (1) (1997) 72-82) is also expressed in the liver, kidney and cells of the
      sympathetic nervous system of the chick embryo (J. Favier, H. Kempf, P. Corvol,
      J.M. Gasc, Cloning and expression pattern of EPAS1 in the chicken embryo.
      Colocalization with tyrosine hydroxylase, FEBS Lett. 462 (1-2) (1999) 19-24).
      Ets1, which expression was originally detected in lymphoid cells of adult
      tissues, has been the first transcription factor to be identified in endothelial
      cells during angiogenesis in the embryo (B. Vandenbunder, L. Pardanaud, T.
      Jaffredo, M.A. Mirabel, D. Stehelin, Complementary patterns of expression of c
      etsl, c-myb and c-myc in the blood-forming system of the chick embryo,
      Development 107 (1989) 265-274 [5]) and in tumours (N. Wernert, M.B. Raes, P.
      Lassalle, M.P. Dehouck, B. Gosselin, B. Vandenbunder, D. Stehelin, The c-ets 1
      proto-oncogene is a transcription factor expressed in endothelial cells during
      tumor vascularisation and other forms of angiogenesis in man, Am. J. Path. 140
      (1992) 119-127 [6]). Since then, the Ets family has extended and this review will
      emphasise the relationships between these factors and angiogenesis.

PMID- 11312109
TI  - Structure and dual function of vascular endothelial growth factor receptor-1 (Flt
      1).
AB  - Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1) is structurally a
      typical tyrosine kinase receptor of about 180 kDa, and carries seven Ig-like
      domains in the extracellular region and a tyrosine kinase domain with a long
      kinase insert. Recent studies have revealed that the VEGFR-1 gene and its gene
      product have several unique characteristics structurally and functionally. In
      addition to the full length receptor, VEGFR-1 gene encodes for a soluble form
      carrying only six Ig domains via an alternative splicing. Both the full length
      and soluble form of VEGFR-1 show strong binding affinity for VEGF, but the kinase
      activity of the full length receptor is one order of magnitude lower than that of
      VEGFR-2 (KDR/Flk-1). Early in embryogenesis, null mutation of VEGFR-1 gene
      results in lethality due to a disorganization of blood vessels and an overgrowth
      of endothelial-like cells, suggesting a regulatory role in vivo. Mice carrying
      the extracellular domain of VEGFR-1 gene without the tyrosine kinase domain
      develop an almost normal circular system and survive. Thus, the extracellular
      region of VEGFR-1 is necessary and sufficient for physiological angiogenesis at
      the early stage of embryogenesis, possibly acting to trap VEGF and suppress VEGF
      levels to an appropriate range. The tyrosine kinase domain of VEGFR-1, although
      much weaker than that of VEGFR-2, transduces signals for endothelial cells.
      Furthermore, VEGFR-1 is involved in the VEGF-dependent migration and gene
      expression of monocyte/macrophages. Therefore, VEGFR-1 functions both in a
      positive and negative manner in different cellular systems and biological
      conditions.

PMID- 11312110
TI  - Novel VEGF family members: VEGF-B, VEGF-C and VEGF-D.
AB  - Vascular endothelial growth factors (VEGFs) constitute a group of structurally
      and functionally related growth factors that modulate many important
      physiological functions of endothelial cells. Currently, five different mammalian
      VEGFs have been identified and they all show unique temporal and spatial
      expression patterns, receptor specificity and function. The VEGFs may play
      pivotal roles in formation of the vascular systems during embryonic development,
      in regulation of capillary growth in normal and pathological conditions in
      adults, and in the maintenance of the normal vasculature. In the future, the
      VEGFs and their receptors may become important therapeutic tools in treatment of
      conditions characterized by aberrant or defective formation of blood vessels and
      lymphatic vessels.

PMID- 11312111
TI  - The chicken Chemotactic and Angiogenic Factor (cCAF), a CXC chemokine.
AB  - The chemokine cCAF (&cmacr;hicken &Cmacr;hemotactic and Angiogenic &Fmacr;actor),
      is the product of the 9E3/CEF4 gene. Its name reflects the biological properties
      of the protein: chemotactic and angiogenic. This CXC chemokine is highly
      homologous to human IL-8, both at the protein and gene level. Molecular modeling
      based on the known structure of IL-8 shows that the structure of cCAF is very
      similar to that of other CXC chemokines. Regulation of expression occurs both at
      the transcriptional and post-transcriptional levels. The cCAF protein is secreted
      very rapidly as a 9kDa molecule and can be cleaved in the N-terminus after
      secretion to produce a smaller form ( approximately 7kDa) that binds to ECM
      molecules. Plasmin, an enzyme present in the early stages of wound healing and in
      tumor stroma, cleaves the 9kDa to the 7kDa form. The biological properties of
      this chemokine and its patterns of expression in vivo strongly suggest that cCAF
      plays important roles in traumatic and pathological conditions.

PMID- 11312112
TI  - Neuropilin in the midst of cell migration and retraction.
AB  - Neuropilin (NRP) is a 140 kDa membrane protein, with a large extracellular domain
      and a short cytoplasmic tail, that was isolated in 1987 from the optic tactum of
      Xenopus laevis. About 10 years after its isolation, NRP was identified as a
      receptor for semaphorin, a family of axonal chemorepellent proteins and for
      vascular endothelial growth factor (VEGF), a family of potent angiogenic factors.
      In the nervous system, NRP forms a high affinity semaphorin-binding complex with
      a receptor tyrosine kinase, plexin, that mediates semaphorin-induced growth cone
      collapse. On the endothelium, NRP is expressed together with KDR, a VEGF receptor
      tyrosine kinase. We have shown that NRP potentiated KDR-mediated endothelial cell
      migration and proliferation. Some tumor cells can express high levels of NRP,
      which is typically their only VEGF receptor, but do not seem to respond to VEGF
      directly. Possible use of NRP as a target for VEGF antagonists, in the context of
      antiangiogenic therapy, are described.

PMID- 11312113
TI  - Ski/Sno and TGF-beta signaling.
AB  - Transforming growth factor-beta is a potent inhibitor of epithelial cell
      proliferation. Proteins involved in TGF-beta signaling are bona fide tumor
      suppressors and many tumor cells acquire the ability to escape TGF-beta growth
      inhibition through the loss of key signaling transducers in the pathway or
      through the activation of oncogenes. Recent studies indicate that there is a
      specific connection between the TGF-beta signaling pathway and the Ski/SnoN
      family of oncoproteins. We summarize evidence that Ski and SnoN directly
      associate with Smad proteins and block the ability of the Smads to activate
      expression of many if not all TGF-beta-responsive genes. This appears to cause
      abrogation of TGF-beta growth inhibition in epithelial cells.

PMID- 11312114
TI  - Control of osteoclastogenesis and bone resorption by members of the TNF family of
      receptors and ligands.
AB  - Skeletal mass is maintained by a balance between cells which resorb bone
      (osteoclasts) and cells which form bone (osteoblasts). Bone development and
      growth is an on-going, life-long process. Bone is formed during embryonic life,
      grows rapidly through childhood, and peaks around 20 years of age (formation
      exceeds resorption). For humans the skeleton then enters a long period,
      approximately 40 years, when bone mass remains relatively stable. Skeletal
      turnover continues but the net effect of resorption and formation on bone mass is
      zero. For women this ends when they enter menopause and similar bone loss occurs
      for men, but later in life. These opposite functions are coupled, resorption
      precedes formation, and osteoblasts, or their precursors, stromal cells, regulate
      osteoclast formation and activity. Until recently, the molecular nature of this
      regulation, was poorly understood. However, recent observations have identified
      members of the TNF family of ligands and receptors as critical regulators of
      osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified.
      Its ligand, receptor activator of nuclear factor-kappaB ligand (RANKL), was
      quickly found, and shown to be expressed on stromal cells and osteoblasts. Its
      cognate receptor, RANK, was found to be expressed in high levels on osteoclast
      precursors. The interaction between RANKL and RANK was shown to be required for
      osteoclast formation. These observations have provided a molecular understanding
      of the coupling between osteoclastic bone resorption and osteoblastic bone
      formation. Moreover, they provide a framework on which to base a clear
      understanding of normal (e.g. postmenopausal osteoporosis and age associated bone
      loss) and pathologic skeletal changes (e.g. osteopetrosis, glucocorticoid-induced
      osteoporosis, periodontal disease, bone metastases, Paget's disease,
      hyperparathyroidism, and rheumatoid arthritis).

PMID- 11312115
TI  - Specificity in cytokine signal transduction: lessons learned from the IL-3/IL
      5/GM-CSF receptor family.
AB  - Cytokines mediate the transduction of proliferative, differentiation and survival
      signals in the hematopoietic system. Although the cytokine family is large and
      diverse, many different cytokines display broadly overlapping functions. This can
      be explained by the fact that cytokine receptors often share multiple subunits.
      Specificity in signal transduction can however be achieved through several
      mechanisms. This review focuses on how signal specificity can be achieved within
      the IL-3, IL-5 and GM-CSF receptor family. This is discussed in terms of receptor
      expression, recent advances in our understanding of intracellular signalling
      components, and analysis of null mutant knock-out mice.

PMID- 11312116
TI  - Soluble interleukin-1 receptor--reverse signaling in innate immunoregulation.
AB  - Interleukin-1 (IL-1) is one of the most important proinflammatory cytokines,
      regulating immunological and inflammatory processes. It induces a very efficient
      and self-amplifying cytokine-network. The action of IL-1 must, therefore, be
      under tight control. Soluble IL-1 receptor was thought to be an efficient
      negative regulator of the IL-1 signaling system. However, recent studies in vitro
      and in vivo demonstrate that soluble IL-1 receptor can act as an agonist as well,
      inducing intracellular signaling events. This feature of soluble IL-1 receptor
      adds a new level of complexity to our understanding of ligand-receptor cross-talk
      and cell-to-cell communication.

PMID- 11312117
TI  - Interleukin-6 and prostate cancer progression.
AB  - Prostate cancer, while initially dependent on androgens for proliferation,
      progresses to an androgen-independent state. Evidence has been accumulating that
      interleukin-6 (IL-6) may contribute to prostate cancer progression. Serum levels
      of IL-6 correlate with prostate tumor burden and patient morbidity. The prostate
      tissue itself appears to be a source of IL-6 and its receptor. Furthermore,
      experimental data suggest that IL-6 is an autocrine and paracrine growth factor
      for androgen-independent prostate cancer cell lines. For example, inhibition of
      IL-6, with anti-IL-6 antibody, sensitizes androgen-independent prostate cancer
      cells to chemotherapeutic agents in vitro. Finally, IL-6 activates a variety of
      signal transduction cascades, some which stimulate androgen receptor activity, in
      prostate cancer cells. These data suggest that targeting IL-6 may have multiple
      benefits in prostate cancer patients.

PMID- 11312118
TI  - The caveolin triad: caveolae biogenesis, cholesterol trafficking, and signal
      transduction.
AB  - Caveolins are a family of proteins that coat the cytoplasmic face of caveolae,
      vesicular invaginations of the plasma membrane. These proteins are central to the
      organization of the proteins and lipids that reside in caveolae. Caveolins
      transport cholesterol to and from caveolae, and they regulate the activity of
      signaling proteins that reside in caveolae. Through studying the genes encoding
      the caveolae coat proteins, we have learned much about how they perform these
      multiple functions.

PMID- 11312119
TI  - Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses
      depending on its cytokine milieu.
AB  - IL-18 is a potent proinflammatory cytokine able to induce IFNgamma, GM-CSF,
      TNFalpha and IL-1 in immunocompetent cells, to activate killing by lymphocytes,
      and to up-regulate the expression of certain chemokine receptors. IL-18 is also
      essential to host defences against severe infections. In particular, the
      clearance of intracellular bacteria, fungi and protozoa requires the induction of
      host-derived IFNgamma, which evokes effector molecules such as nitric oxide.
      Also, IL-18 plays a part in the clearance of viruses, partly by the induction of
      cytotoxic T cells, and the expulsion of viruses is impaired in IL-18-deficient
      mice. IL-18 also enhances tumour rejection by its potent capacity to augment the
      cytotoxic activity of NK and T cells in vivo. In contrast, recent studies also
      demonstrate a convincing role for IL-18 in atopic responses, including atopic
      asthma. IL-18 induces naive T cells to develop into Th2 cells. Moreover, IL-18
      also induces IL-13 and/or IL-4 production by NK cells, mast cells and basophils.
      Therefore, IL-18 should be seen as a unique cytokine that enhances innate
      immunity and both Th1- and Th2-driven immune responses.

PMID- 11312120
TI  - NF-kappaB and cell-cycle regulation: the cyclin connection.
AB  - The cyclins are a family of proteins that are centrally involved in cell cycle
      regulation and which are structurally identified by conserved "cyclin box"
      regions. They are regulatory subunits of holoenzyme cyclin-dependent kinase (CDK)
      complexes controlling progression through cell cycle checkpoints by
      phosphorylating and inactivating target substrates. CDK activity is controlled by
      cyclin abundance and subcellular location and by the activity of two families of
      inhibitors, the cyclin-dependent kinase inhibitors (CKI). Many hormones and
      growth factors influence cell growth through signal transduction pathways that
      modify the activity of the cyclins. Dysregulated cyclin activity in transformed
      cells contributes to accelerated cell cycle progression and may arise because of
      dysregulated activity in pathways that control the abundance of a cyclin or
      because of loss-of-function mutations in inhibitory proteins.Analysis of
      transformed cells and cells undergoing mitogen-stimulated growth implicate
      proteins of the NF-kappaB family in cell cycle regulation, through actions on the
      CDK/CKI system. The mammalian members of this family are Rel-A (p65), NF
      kappaB(1) (p50; p105), NF-kappaB(2) (p52; p100), c-Rel and Rel-B. These proteins
      are structurally identified by an amino-terminal region of about 300 amino acids,
      known as the Rel-homology domain. They exist in cytoplasmic complexes with
      inhibitory proteins of the IkappaB family, and translocate to the nucleus to act
      as transcription factors when activated. NF-kappaB pathway activation occurs
      during transformation induced by a number of classical oncogenes, including
      Bcr/Abl, Ras and Rac, and is necessary for full transforming potential. The avian
      viral oncogene, v-Rel is an NF-kappaB protein. The best explored link between NF
      kappaB activation and cell cycle progression involves cyclin D(1), a cyclin which
      is expressed relatively early in the cell cycle and which is crucial to
      commitment to DNA synthesis. This review examines the interactions between NF
      kappaB signaling and the CDK/CKI system in cell cycle progression in normal and
      transformed cells. The growth-promoting actions of NF-kappaB factors are
      accompanied, in some instances, by inhibition of cellular differentiation and by
      inhibition of programmed cell death, which involve related response pathways and
      which contribute to the overall increase in mass of undifferentiated tissue.

PMID- 11312121
TI  - Pleiotropic roles of formyl peptide receptors.
AB  - FPR and FPRL1 belong to the seven-transmembrane, G protein-coupled
      chemoattractant receptor superfamily. Because of their capacity to interact with
      bacterial chemotactic formylated peptides, these receptors are thought to play a
      role in host defense against microbial infection. Recently, a variety of novel
      agonists have been identified for these receptors, including several host-derived
      endogenous molecules that are involved in proinflammatory responses. Most notably
      is the use of FPRL1 by at least three amyloidogenic protein and peptide ligands,
      the serum amyloid A (SAA), the 42 amino acid form of beta amyloid (Abeta(42)),
      and the prion peptide PrP106-126, to chemoattract and activate human phagocytic
      leukocytes. These new findings have greatly expanded the functional scope of the
      formyl peptide receptors and call for more in-depth investigation of the role of
      these receptors in pathophysiological conditions.

PMID- 11312122
TI  - Expression profiling in knockout mice: lymphotoxin versus tumor necrosis factor
      in the maintenance of splenic microarchitecture.
AB  - Expression profiling provides a powerful approach to define the underlying
      molecular mechanisms in disease. Several techniques referred collectively to as
      gene profiling may be also helpful in the analysis of the phenotype of mice with
      targeted mutations, especially if applied to distinct histological compartments,
      to specific cell types or to evaluate the effect of specific challenges, such as
      infection. Here we review several of the existing techniques applicable to
      genetic knockout studies, and share our experience from the study of mice with
      tumor necrosis factor (TNF) and lymphotoxin (LT) deficiencies, with specific
      emphasis on the distinction between TNF- and LT-mediated signalling pathways in
      vivo. Gene expression profiling analysis of TNF/LT-deficient mice supports the
      notion that TNF and LT, originally discovered as distinct biological activities,
      manifest both distinct and redundant functions in vivo.

PMID- 11312124
TI  - Web alert. Physiology and metabolism.

PMID- 11312126
TI  - Virus-mediated reprogramming of gene expression in plants.
AB  - Plant viruses have made many significant contributions to plant biology over the
      years: they have provided plant researchers with functional promoters, transient
      expression systems and, most recently, with critical insights into the phenomenon
      of posttranscriptional gene silencing. Plant virus expression vectors have the
      ability to either overexpress genes or suppress gene expression in plants.
      Whereas the 'rules' for gene expression are generally understood conceptually,
      the mechanisms for the induction of gene silencing are less well understood.
      Recent advances in the understanding of both the biological role and the mode of
      action of posttranscriptional gene silencing will affect both the design and the
      use of plant viral vectors and transgenic plants for either gene-overexpression
      or gene-silencing applications.

PMID- 11312127
TI  - A systematic approach to biochemical profiling.
AB  - Sequencing of the Arabidopsis thaliana genome is complete. The analytical tools
      for determining gene function by altering and monitoring gene expression are
      relatively well developed, and are generating large volumes of valuable data.
      Recent advances in techniques for the analysis of small molecules allow
      researchers to apply biochemical profiling as another powerful approach to
      functional genomics and metabolic research.

PMID- 11312128
TI  - NMR and plant metabolism.
AB  - Recent advances in NMR methodology offer a way to acquire a comprehensive profile
      of a wide range of metabolites from various plant tissues or cells. NMR is a
      powerful approach for plant metabolite profiling and provides a capacity for the
      dynamic exploration of plant metabolism that is virtually unmatched by any other
      analytical technique.

PMID- 11312129
TI  - High resolution spatial analysis of plant systems.
AB  - Analysis of organisms using techniques that provide high spatial and temporal
      resolution is of increasing interest in many disciplines of biomedical research.
      Although the examination of animal tissues has been the main focus to date, the
      recent development and improvement of methods for the sampling and handling of
      single cells and for their biochemical analysis now provide tools for
      investigating plant as well as animal cells.

PMID- 11312130
TI  - The phloem as a conduit for inter-organ communication.
AB  - The plant vascular system plays a pivotal role in the delivery of nutrients to
      distantly located organs. Recent discoveries have provided new insight into a
      novel role for plasmodesmata and the phloem in terms of the transport and
      delivery of information macromolecules (i.e. proteins and ribonucleoprotein
      complexes). Non-cell/organ-autonomous control over gene expression may function
      both in defense signaling and developmental programming in plants.

PMID- 11312131
TI  - Carotenoid biosynthesis in flowering plants.
AB  - The general scheme of carotenoid biosynthesis has been known for more than three
      decades. However, molecular description of the pathway in plants began only in
      the 1990s after the genes for the carotenogenic enzymes were cloned. Recent data
      on the biochemistry of carotenogenesis and its regulation in vivo present the
      possibility of genetically manipulating this pathway in crop plants.

PMID- 11312132
TI  - Plant glycosyltransferases.
AB  - Glycosyltransferases are involved in the biosyntheses of cell-wall
      polysaccharides, the addition of N-linked glycans to glycoproteins, and the
      attachment of sugar moieties to various small molecules such as hormones and
      flavonoids. In the past two years, substantial progress has been made in the
      identification and cloning of genes that encode glycosyltransferases. Moreover,
      analysis of the recently completed Arabidopsis genome sequence indicates the
      existence of several hundred additional genes encoding putative
      glycosyltransferases.

PMID- 11312133
TI  - The expanding universe of alkaloid biosynthesis.
AB  - Characterization of many of the major gene families responsible for the
      generation of central intermediates and for their decoration, together with the
      development of large genomics and proteomics databases, has revolutionized our
      capability to identify exotic and interesting natural-product pathways. Over the
      next few years, these tools will facilitate dramatic advances in our knowledge of
      the biosynthesis of alkaloids, which will far surpass that which we have learned
      in the past 50 years. These tools will also be exploited for the rapid
      characterization of regulatory genes, which control the development of
      specialized cell factories for alkaloid biosynthesis.

PMID- 11312134
TI  - Metabolism of tyrosine and tryptophan--new genes for old pathways.
AB  - Tyrosine and tryptophan are precursors for the plant defense compounds dhurrin
      and indole glucosinolates, respectively. In addition, tryptophan is a precursor
      for the essential phytohormone indole-3-acetic acid. Recent advances in
      understanding the biosynthesis of these compounds have come from the
      characterization of enzymes that catalyze the N-hydroxylation of the precursor
      amino acid to the oxime intermediate. Furthermore, enzymes catalyzing subsequent
      biosynthetic steps have also been identified.

PMID- 11312135
TI  - Temperature sensing and cold acclimation.
AB  - The fundamental question in cold acclimation is how do plants perceive the low
      but nonfreezing temperatures that activate cold acclimation responses. New
      findings in the past year suggest that changes in membrane fluidity, cytoskeleton
      rearrangement, and calcium influxes are among the earliest events taking place in
      plants upon exposure to low nonfreezing temperatures. In the cyanobacterium
      Synechocystis PCC6803, temperature change is detected by at least two separate
      sensors. One of these measures membrane fluidity using a classical two-component
      system involving histidine kinases and a response regulator in a His-to-Asp
      phosphorelay. Although these Synechocystis results may not be directly relevant
      to cold acclimation, they can guide our thinking as we search for biological
      thermometers in higher plants.

PMID- 11312136
TI  - Carbon and nitrogen sensing and signaling in plants: emerging 'matrix effects'.
AB  - Plants, like other organisms, have developed mechanisms that allow them to sense
      and respond to changes in levels of carbon and nitrogen metabolites. These
      mechanisms, in turn, regulate the expression of genes and the activities of
      proteins involved in C and N transport and metabolism, allowing plants to
      optimize the use of energy resources. Recent studies, which have involved
      molecular-genetic, genomic, and cell biological approaches, have begun to uncover
      the signals and components of C:N sensing and signaling mechanisms in plants. For
      sugar sensing, analysis of Arabidopsis mutants has revealed intersections with
      hormone and nitrogen signaling. For nitrogen sensing/signaling, recent progress
      has identified transcriptional and posttranslational mechanisms of regulation. In
      all, a complex picture is emerging in which C:N signaling systems are subject to
      a 'matrix effect' in which downstream responses are dependent upon cell-type,
      developmental, metabolic, and/or environmental conditions.

PMID- 11312137
TI  - Proteases and cellular regulation in plants.
AB  - Protein degradation is accomplished by a diverse collection of proteases. Recent
      studies have illustrated the importance of proteolysis in the control of many
      aspects of cellular regulation from photosynthesis to photomorphogenesis. In
      addition, new results point to a role for proteolysis in programmed cell death,
      circadian rhythm, and defense response in plants.

PMID- 11312138
TI  - Lysine catabolism: a stress and development super-regulated metabolic pathway.
AB  - Lysine is a nutritionally important essential amino acid whose level in plants is
      largely regulated by the rate of its synthesis. In some plant tissues and under
      some stress conditions, however, lysine is also efficiently catabolized into
      glutamate and several other stress-related metabolites by novel mechanisms of
      metabolic regulation. Lysine catabolism is important for mammalian brain
      function; it is possible that the generation of glutamate regulates nerve
      transmission signals via glutamate receptors. Plants also possess homologues of
      animal glutamate receptors. It is thus likely that lysine catabolism also
      regulates various plant processes via these receptors.

PMID- 11312139
TI  - Hormones and the hippocampus.
AB  - Hippocampal lesions produce memory deficits, but the exact function of the
      hippocampus remains obscure. Evidence is presented that its role in memory may be
      ancillary to physiological regulation. Molecular studies demonstrate that the
      hippocampus is a primary target for ligands that reflect body physiology,
      including ion balance and blood pressure, immunity, pain, reproductive status,
      satiety and stress. Hippocampal receptors are functional, probably accessible to
      their ligands, and mediate physiological and cognitive changes. This argues that
      an early role of the hippocampus may have been in sensing soluble molecules
      (termed here 'enteroception') in blood and cerebrospinal fluid, perhaps
      reflecting a common evolutionary origin with the olfactory system
      ('exteroception'). Functionally, hippocampal enteroception may reflect feedback
      control; evidence is reviewed that the hippocampus modulates body physiology,
      including the activity of the hypothalamus-pituitary-adrenal axis, blood
      pressure, immunity, and reproductive function. It is suggested that the
      hippocampus operates, in parallel with the amygdala, to modulate body physiology
      in response to cognitive stimuli. Hippocampal outputs are predominantly
      inhibitory on downstream neuroendocrine activity; increased synaptic efficacy in
      the hippocampus (e.g. long-term potentiation) could facilitate throughput
      inhibition. This may have implications for the role of the hippocampus and long
      term potentiation in memory.

PMID- 11312140
TI  - Cholecystokinin expression in the developing and regenerating pancreas and
      intestine.
AB  - In developmental terms, the endocrine system of neither the gut nor the
      pancreatic islets has been characterized fully. Little is known about the
      involvement of cholecystokinin (CCK), a gut hormone, involved in regulating the
      secretion of pancreatic hormones, and pancreatic growth. Here, we tracked CCK
      expressing cells in the intestines and pancreata of normal mice (BALB/c), Non
      Obese Diabetic (NOD) mice and interferon (IFN)-gamma transgenic mice, which
      exhibit pancreatic regeneration, during embryonic development, the postnatal
      period and adulthood. We also questioned whether IFN-gamma influences the
      expression of CCK. The results from embryonic day 16 showed that all three
      strains had CCK in the acinar region of pancreata, and specifically in alpha
      cells that also expressed glucagon. However, in adulthood only BALB/c and NOD
      mice continued this pattern. By contrast, in IFN-gamma transgenic mice, CCK
      expression was suppressed from birth to 3 months of age in the pancreata but not
      intestines. However, by 5 months of age, CCK expression appeared in the
      regenerating pancreatic ductal region of IFN-gamma transgenic mice. In the
      intestine, CCK expression persisted from fetus to adulthood and was not
      influenced by IFN-gamma. Intestinal cells expressing CCK did not co-express
      glucagon, suggesting that these cells are phenotypically distinct from CCK
      expressing cells in the pancreatic islets, and the effect of IFN-gamma on CCK
      varies depending upon the cytokine's specific microenvironment.

PMID- 11312141
TI  - Immunocytochemical demonstration of oestrogen receptor beta in blood vessels of
      the female rat.
AB  - The role of oestrogen receptor (ER) beta in vascular function remains unclear.
      With the use of a specific ERbeta antibody we have now, using
      immunocytochemistry, visualized ERbeta in different parts of the vascular tree.
      In about 70% of medial smooth muscle cells of female rat aorta, tail artery and
      uterine artery, nuclear immunoreactivity to ERbeta was observed. In these vessels
      endothelial cells also expressed ERbeta. Vascular expression of the ERalpha
      subtype was lower than that of ERbeta. In aorta and tail artery, no
      immunoreactivity towards ERalpha was observed, while in uterine vessels
      occasional medial smooth muscle and endothelial cells expressed this ER subtype.
      ERbeta and alpha expression in uterine vessels was independent of the stage of
      the oestrous cycle, suggesting that variations in uterine blood flow occurring
      during the cycle are independent of ER density. The regional distribution of
      ERalpha, as determined by immunocytochemistry, was supported by measurements of
      ERalpha levels by enzyme immunoassay. In the uterine artery, the level of ERalpha
      was several times higher (P<0.001) than that of aorta and tail artery (10.1+/-1.7
      fmol/mg protein in the uterine artery vs 3.3+/-1.0 and 0.5+/-0.5 fmol/mg protein
      in aorta and tail artery respectively). Thus, a prominent nuclear expression of
      ERbeta was observed in the vascular wall of several parts of the vascular tree,
      while ERalpha predominantly was expressed in uterine vessels, suggesting that
      ERbeta and alpha may have different roles in vascular function.

PMID- 11312142
TI  - Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour
      cells.
AB  - The oestrogen receptor is fundamental to the growth and survival of the rat
      pituitary tumour cell line, GH(3). Our previous studies have shown that
      antioestrogens such as RU 58668 and ZM 182780 will reduce the rate of cell
      division and also induce cell death. Death of these cells in response to
      antioestrogen treatment appears to be due to a heightened sensitivity to reactive
      oxygen species (ROS). As part of a study to determine the cross-talk between
      steroid receptor systems in these cells, we have observed that the
      glucocorticoid, dexamethasone (Dex), inhibits antioestrogen-induced cell death.
      Cell death induced by H(2)O(2) is enhanced by ZM 182780 and this effect is also
      blocked by Dex. As apoptotic cell death in a number of systems involves an early
      loss of mitochondrial membrane potential (DeltaPsi(m)), we have performed
      detailed studies on the time-course of DeltaPsi(m) loss in relation to the loss
      in cell membrane function. These studies have indicated that a loss of
      DeltaPsi(m) parallels a loss of cell membrane function - this is more
      characteristic of necrosis than of apoptosis. From microscopic observations of
      these cells in response to H(2)O(2), it has been noted that early cell membrane
      blebbing, induced by H(2)O(2), is blocked in the presence of ZM 182780. Cell
      membrane blebbing can precede necrosis as well as apoptosis and it is thought to
      involve cytoskeletal changes, for which localised glycolytic reactions provide
      ATP. These observations, together with those showing that removal of glucose, but
      not inhibition of mitochondrial function, enhances ROS-induced cell death,
      prompted studies on the glycolytic pathway. As a strong candidate mechanism, it
      would appear that, via an effect on one of the rate-limiting glycolytic enzymes,
      glyceraldehyde-3-phosphate dehydrogenase, Dex is able to overcome the
      antioestrogen-enhanced loss of glycolytic function following exposure of cells to
      ROS. This report contributes to the growing body of evidence showing that
      glucocorticoids provide a survival advantage to both normal and tumour cell
      types.

PMID- 11312143
TI  - Anterior pituitary trophic responses to dexamethasone withdrawal and repeated
      dexamethasone exposures.
AB  - Glucocorticoid withdrawal, depending on the dose and duration of treatment,
      results in a transient but sometimes prolonged reduction in hypothalamo-pituitary
      adrenal (HPA) axis secretory responsiveness. As the anatomic basis of HPA axis
      suppression remains uncertain, we have directly examined changes in trophic
      activity within the rat anterior pituitary gland following dexamethasone
      withdrawal and re-treatment. Treatment of adrenalectomised, male Wistar rats with
      dexamethasone results in a discrete, highly significant burst of apoptosis in the
      anterior pituitary with concurrent suppression of mitosis. Despite a surge in
      mitotic activity immediately after dexamethasone withdrawal, calculated total
      anterior pituitary cell populations remain below that seen in untreated
      adrenalectomised controls. Repeated exposures to dexamethasone show that the
      dexamethasone-sensitive cell population that is deleted by apoptosis is partially
      but not completely restored. As the amplitude of apoptotic bursts induced by
      second and third dexamethasone exposures are similar but smaller than that
      induced by initial exposure, it appears that the very first exposure to
      dexamethasone deletes a subset of anterior pituitary cells that are either not
      restored at all, or are only replaced very slowly. The reduced proportion of
      corticotrophs contributing to the increase in mitotic index after dexamethasone
      withdrawal corroborates this. Although continued cell turnover within the
      pituitary predicts that the absolute cellular deficit would diminish with time,
      the effects seen may contribute to the delayed recovery of pituitary axis
      function following cessation of glucocorticoid treatment.

PMID- 11312144
TI  - Identification of beta-endorphins in the pituitary gland and blood plasma of the
      common carp (Cyprinus carpio).
AB  - Carp beta-endorphin is posttranslationally modified by N-terminal acetylation and
      C-terminal cleavage. These processes determine the biological activity of the
      beta-endorphins. Forms of beta-endorphin were identified in the pars intermedia
      and the pars distalis of the pituitary gland of the common carp (Cyprinus
      carpio), as well as the forms released in vitro and into the blood. After
      separation and quantitation by high performance liquid chromatography (HPLC)
      coupled with radioimmunoassay, the beta-endorphin immunoreactive products were
      identified by electrospray ionisation mass spectrometry and peptide sequencing.
      The release of beta-endorphins by the pituitary gland was studied after
      stimulation with corticotrophin-releasing factor (CRF) in vitro. In the pars
      intermedia, eight N-acetylated truncated forms were identified. Full length N
      acetyl beta-endorphin(1-33) coeluted with N-acetyl beta-endorphin(1-29) and these
      forms together amounted to over 50% of total immunoreactivity. These products
      were partially processed to N-acetyl betaendorphin(1-15) (30.8% of total
      immunoreactivity) and N-acetyl beta-endorphin(1-10) (3.1%) via two different
      cleavage pathways. The acetylated carp homologues of mammalian alpha- and gamma
      endorphin were also found. N-acetyl beta-endorphin(1-15) and (1-29) and/or (1-33)
      were the major products to be released in vitro, and were the only acetylated
      beta-endorphins found in blood plasma, although never together. CRF stimulated
      the release of opioid beta-endorphin from the pars distalis. This non-acetylated
      beta-endorphin represents the full length peptide and is the most abundant form
      in plasma.

PMID- 11312145
TI  - Retinoid nutritional status differently affects the expression of Japanese quail
      retinoic acid receptor-beta isoform transcripts in a tissue-specific manner.
AB  - We investigated the effects of vitamin A (VA) nutritional status on the levels of
      expression of retinoic acid (RA) receptor-beta (RARbeta) gene in the various
      tissues of Japanese quail. VA deficiency caused a significant decrease in the
      mRNA levels of brain, liver, heart, lung and kidney RARbeta2/beta4, whereas no
      change was observed in the level of testis RARbeta2 transcript. In contrast,
      reduction in the RARbeta1 transcript caused by VA depletion was observed only in
      the lung, remaining unchanged in the other tissues. The administration of RA to
      the VA-deficient quail rapidly induced the expression of RARbeta2/beta4 mRNAs in
      all the tissues examined, but RA increased the expression of RARbeta1 transcript
      in the liver, heart, lung and kidney at a lower magnitude. RA could not change
      the expression of the brain RARbeta1 transcript, while it induced the expression
      of the testis RARbeta1 mRNA in a temporal way. These results clearly indicate
      that VA nutritional status differently regulates the expression of RARbeta1 and
      RARbeta2/beta4 transcripts in a tissue-specific manner.

PMID- 11312146
TI  - Progesterone and testosterone in combination act in the hypothalamus of castrated
      rams to regulate the secretion of LH.
AB  - We tested the hypotheses that progesterone enhances the negative feedback actions
      of testosterone in rams and that this occurs through actions at the hypothalamus.
      In the first part of this study, blood samples were collected every 10 min for 12
      h before and after 7 days of treatment (i.m.) of castrated Romney Marsh rams (n=5
      per group) with vehicle, progesterone (4 mg/12 h), testosterone (4 mg/12 h) or a
      combination of progesterone (4 mg/12 h) and testosterone (4 mg/12 h). In the
      second part of this study the brains of four gonad-intact Romney Marsh rams were
      collected, the hypothalamus was sectioned and in situ hybridisation of mRNA for
      progesterone receptors conducted. After 7 days of treatment with vehicle or
      progesterone or testosterone alone, there were no changes in the secretion of LH.
      In contrast, treatment with a combination of progesterone and testosterone
      resulted in a significant (P<0.01, repeated measures ANOVA) decrease in mean
      plasma concentrations of LH, the number of LH pulses per hour and the pre-LH
      pulse nadir and a significant (P<0.01) increase in the inter-LH pulse interval.
      We found cells containing mRNA for progesterone receptors throughout the
      hypothalamus, including the preoptic area (where most GnRH neurons are located in
      sheep), the periventricular, ventromedial and arcuate nuclei and the bed nucleus
      of the stria terminalis. This study shows that progesterone is capable of acting
      centrally with testosterone to suppress the secretion of LH in castrated rams and
      that cells containing mRNA for progesterone receptors are located in the
      hypothalamus of rams in the vicinity of GnRH neurons.

PMID- 11312147
TI  - Testosterone receptor blockade restores cellular immunity in male mice after burn
      injury.
AB  - Males are known to have increased risk for septic complications after traumatic
      injury, which appears to be mediated by the inhibitory effects of testosterone on
      immune function. The role of testosterone in immunity after burn injury, however,
      remains unclear. Herein, we examined the effects of a testosterone receptor
      antagonist, flutamide, on delayed type hypersensitivity response (DTH),
      splenocyte proliferation, interleukin (IL)-2 secretion, and IL-2 receptor (IL-2R)
      expression in male BALB/c mice subjected to a 15% total body surface area burn or
      sham injury. Burn- or sham-injured mice were given flutamide s.c. at 30 min and
      24 h after injury. At 48 h, burn injury caused a 48% (P<0.001) decrease in DTH
      response; however, mice that received flutamide treatment did not demonstrate
      significant suppression of DTH. Likewise, splenocyte proliferation and IL-2
      production were depressed in burned animals in comparison with sham-injured
      controls, and flutamide treatment resulted in a partial restoration of these
      responses. In vitro studies indicated that splenocytes from sham- and burn
      injured mice were equally sensitive to the suppressive effects of 5alpha
      dihydrotestosterone in regard to proliferation and IL-2 production. Further
      evaluation revealed a decrease in IL-2R expression on splenocytes from burned
      mice and a partial restoration of this expression with flutamide treatment. Thus
      blocking testosterone receptor activation improves the cellular immunity in
      thermally injured mice, possibly through restoration of IL-2 production and IL-2R
      expression. It remains to be determined whether the effects of testosterone in
      this injury model are direct or indirect.

PMID- 11312148
TI  - The steroid receptor antagonists RU40555 and RU486 activate glucocorticoid
      receptor translocation and are not excreted by the steroid hormones transporter
      in L929 cells.
AB  - RU40555 is a recently available glucocorticoid receptor (GR) antagonist that
      differs from RU486 by a methyl radical. We have used the mouse fibroblast cell
      line L929 to study the in vitro effects of RU40555 on GR translocation and
      function and on the membrane steroid hormones transporter. The results showed
      that: 1) RU40555 competed for the binding of labelled dexamethasone (Dex) with a
      K(i) of 2.4 nM; 2) both RU40555 and RU486 were equally potent inhibitors of Dex
      induced GR-mediated gene transcription; 3) maximum GR translocation induced by
      micromolar concentrations of Dex and the GR antagonists was approximately 30-55%
      loss in the cytoplasmic GR and approximately 40-90% increase in the nuclear GR
      (assessed by GR immunostaining in cytoplasm and nucleus and western blots of
      immunoprecipitated GR protein in cytosolic and nuclear fractions) and was similar
      for the two antagonists; 4) at nanomolar concentrations, RU40555 and RU486
      induced more GR translocation than Dex (assessed by [(3)H]Dex binding and western
      blot of immunoreactive GR in the same cytosolic homogenates); 5) blocking the
      steroids membrane transporter with verapamil (100 microM) in the presence of Dex
      (10 nM) increased GR translocation to levels similar to those induced by RU40555
      (10 nM) and RU486 (10 nM) alone; 6) verapamil did not affect GR translocation in
      the presence of RU40555 or RU486. These data demonstrate similar quantitative
      effects on GR translocation by RU486 and the new GR antagonist, RU40555.
      Moreover, RU40555, like RU486, is an effective GR antagonist. Finally, there is
      no evidence that the intracellular concentrations of RU40555 or RU486 are
      regulated by the steroids membrane transporter in L929 cells.

PMID- 11312149
TI  - Contribution of progesterone, follicle stimulating hormone and glucocorticoids in
      survival of serum-free cultured granulosa cell explants.
AB  - To investigate the role of progesterone (P4) as a survival factor in quail
      granulosa cell explants, P4 content was determined under various conditions and
      correlated with apoptotic indexes (AIs) evaluated by 2',6'-diamidino-2
      phenylindole (DAPI)-staining. Analysis of serum-free cultures from 24 to 96 h
      shows decreased P4 levels in the medium paralleled by increasing AI. Inhibiting
      apoptosis by gonadotropic support (FSH, 100 ng/ml) stimulates a 3-fold increase
      of the P4 level in the medium (83.49+/-8.69 vs 26.31+/-1.61 ng/ml in serum-free
      controls) together with a significant decrease in AI from 8.81+/-1.06% in serum
      free controls to 3.50+/-0.72%. Substantial evidence for P4 as an
      autocrine/paracrine survival factor can be inferred from experiments with
      aminoglutethimide (AG, 1 mM) and RU486 (20 microM). Blocking P4 synthesis by AG
      causes a 2-fold increase in apoptosis from 6.08+/-0.67% in serum-free controls to
      12.53+/-1.60%. Blocking P4 receptors by RU486 causes a similar increase in AI
      (3.02+/-0.98% in serum-free controls to 17.07+/-3.20%) and about a 50% decrease
      in P4. The effect of RU486 could be attenuated by exogenous P4 but not by
      dexamethasone indicating selective binding of P4 to the progesterone receptor.
      Dexamethasone treatment promotes survival without affecting P4 levels. In further
      support of an autocrine/paracrine action for P4 in the granulosa cells, both the
      A and B form of the avian P4 receptor (PR) are identified in vivo and in vitro by
      Western blotting. Exogenous administration of P4 only affects survival when
      endogenous P4 synthesis is blocked or after 48 h of serum-free culture when
      endogenous P4 production is very low. Because FSH also affects survival when its
      stimulatory effect on P4 synthesis is blocked by AG (AI decrease from 6.08+/
      0.67% in serum-free controls to 1.64+/-0.71% in FSH+AG treated) it is proposed
      that (1) P4 is an autocrine/paracrine survival factor in the preovulatory
      granulosa and (2) FSH mediates both P4-dependent and P4-independent survival
      pathways.

PMID- 11312150
TI  - Inhibin A is a follicle stimulating hormone-responsive marker of granulosa cell
      differentiation, which has both autocrine and paracrine actions in sheep.
AB  - The aim of these studies was to examine the origin, control and local actions of
      inhibin A in monovular species, using the sheep as a model. Experiment 1 examined
      the pattern of mRNA expression for the inhibin subunits in relation to follicular
      size and pattern of expression to other differentiative markers in granulosa
      (P450 aromatase) and thecal cells (P450 17alpha-hydroxylase). Experiment 2
      examined the pattern of inhibin A production, in relation to oestradiol, by
      granulosa cells induced to differentiate in vitro with follicle-stimulating
      hormone (FSH). Experiment 3 examined possible paracrine and autocrine actions of
      inhibin A by determining the effect of addition of human recombinant inhibin A
      and/or antiserum to inhibin on gonadotrophin-stimulated cellular differentiation.
      The results of Experiment 1 showed that expression of mRNA encoding inhibin
      subnuits alpha, beta(A) and beta(B) is greater (P<0.05) in large oestrogenic
      follicles than in small follicles but that only expression of the inhibin beta(A)
      subunit differs (P<0.05) between large oestrogenic and non-oestrogenic follicles.
      Expression of 17alpha-hydroxylase, but not of the luteinising hormone (LH)
      receptor, in thecal cells was related to both the size and the oestrogenicity of
      antral follicles, in a manner similar to that of the inhibin subunits. Experiment
      2 demonstrated that the production of inhibin A by sheep granulosa cells is FSH
      responsive after prolonged exposure (P<0.001) and precedes the production of
      oestradiol by around 48 h in the differentiative cascade induced in granulosa
      cells by FSH. The results of Experiment 3 showed that inhibin A can augment
      gonadotrophin-stimulated steroid production by both granulosa and theca cells
      (P<0.01), and that the addition of antiserum to inhibin can inhibit FSH
      stimulated oestradiol production by granulosa cells from both small and large
      follicles (P<0.001). We conclude that inhibin A is an FSH-responsive marker of
      granulosa cell differentiation which has both autocrine and paracrine actions in
      sheep.

PMID- 11312151
TI  - Extracellular matrix regulates ovine granulosa cell survival, proliferation and
      steroidogenesis: relationships between cell shape and function.
AB  - The extracellular matrix (ECM), constituting the follicular basal lamina and
      present also between follicular cells and in the follicular fluid, is believed to
      regulate granulosa cell (GC) function during follicular development. Ovine GCs
      isolated from small (1-3 mm in diameter) or large (4-7 mm in diameter) antral
      follicles were cultured on various pure ECM components (type I collagen,
      fibronectin, laminin), synthetic substrata enhancing (RGD peptides) or impairing
      (poly 2-hydroxyethylmethacrylate (poly-hema)) cell adhesion, or in the presence
      of heparin. The effects of these factors, used alone or in combination with IGF-I
      and/or FSH, were evaluated in terms of GC spread, survival, proliferation and
      steroidogenesis. When grown on type I collagen (CI) gel, poly-hema or heparin,
      GCs from both large and small follicles exhibited a round shape and a low
      proliferation rate. Compared with non-coated plastic substratum as a control,
      these ECM or synthetic compounds enhanced estradiol secretion and reduced
      progesterone secretion by large-follicle GCs. In contrast, GCs from both large
      and small follicles spread extensively on CI coating, fibronectin, laminin and
      RGD peptides. Fibronectin and laminin dramatically increased the proliferation
      rate and enhanced survival of GCs from both origins. Moreover, fibronectin,
      laminin and RGD peptides reduced estradiol secretion by large-follicle GCs.
      Unexpectedly, CI coating increased estradiol secretion and reduced progesterone
      secretion by large-follicle GCs, suggesting that type I collagen was able to
      maintain estradiol secretion independently of GC shape. Finally, GC
      responsiveness to IGF-I and FSH, in terms of proliferation and steroidogenesis,
      was generally maintained when cells were grown on ECM components, RGD peptides
      and in the presence of heparin. However, when large-follicle GCs were grown as
      non-adherent clusters (as observed on poly-hema) basal and IGF-I- and/or FSH
      stimulated progesterone secretions were totally abolished. Overall, this study
      shows that GC shape, survival, proliferation and steroidogenesis can be modulated
      in vitro by pure ECM components in a specific and coordinated manner. It is
      suggested that, in vivo, fibronectin and laminin would sustain follicular
      development by enhancing the survival and proliferation of GCs, whereas type I
      collagen might participate in the maintenance of estradiol secretion in large
      antral follicles.

PMID- 11312152
TI  - Autoregulation of the gonadotropin-releasing hormone (GnRH) system during
      puberty: effects of antagonistic versus agonistic GnRH analogs in a female rat
      model.
AB  - To address whether gonadotropin-releasing hormone (GnRH) regulates its own
      expression and the expression of its receptor in the hypothalamus and ovary, we
      treated five groups of prepubertal/peripubertal female rats from postnatal days
      25-36 with either the GnRH agonist triptorelin (TRIP) or the GnRH antagonist
      cetrorelix (CET), each 10 or 100 microgram/day, or a placebo. We compared their
      effects regarding pubertal development, serum gonadotropins and the expression of
      GnRH and GnRH-receptor in the hypothalamus, pituitary, ovary and uterus. Onset of
      puberty was determined by vaginal opening, and expression levels of GnRH and GnRH
      receptor were determined using either quantitative real-time PCR or competitive
      RT-PCR. Onset of puberty was retarded by both analogs but CET (100 microgram/day)
      inhibited while TRIP (10 and 100 microgram/day) stimulated serum gonadotropins
      (P<0.05). The expression of GnRH in the preoptic area did not show significant
      differences among the treatment groups but ovarian GnRH mRNA levels were
      significantly stimulated by CET (100 microgram/day). GnRH mRNA could not be
      detected in the uterus by either real-time PCR or competetive RT-PCR. The GnRH
      receptor expression in the hypothalamus (preoptic area and mediobasal
      hypothalamus) did not vary among any of the groups, whereas in the pituitary GnRH
      receptor mRNA levels were stimulated by TRIP (10 microgram/day) but inhibited by
      CET (100 microgram/day). In contrast, in the ovary GnRH-receptor mRNA levels were
      inhibited by both TRIP (100 microgram/day) and CET (100 microgram/day).
      Interestingly, the GnRH-receptor was even expressed in the uterus where it was
      strongly stimulated by both CET and TRIP in a dose-related manner. This shows
      that in addition to their different pituitary effects, the GnRH analogs
      cetrorelix and triptorelin exert different actions at the hypothalamic, ovarian
      and uterine level. This study also demonstrates an organ-specific regulation of
      GnRH and GnRH-receptor gene expression which is likely part of a local
      autoregulatory system. We conclude that the ovarian and uterine effects of GnRH
      analogs must be considered in addition to their known pituitary effects when
      deciding which GnRH analog is most suitable for treating precocious puberty.

PMID- 11312153
TI  - Myocardial gene expression of glucose transporter 1 and glucose transporter 4 in
      response to uteroplacental insufficiency in the rat.
AB  - Uteroplacental insufficiency causes intrauterine growth retardation (IUGR) and
      subsequent low birth weight, which predisposes the affected newborn towards adult
      Syndrome X. Individuals with Syndrome X suffer increased morbidity from adult
      ischemic heart disease. Myocardial ischemia initiates a defensive increase in
      cardiac glucose metabolism, and individuals with Syndrome X demonstrate reduced
      insulin sensitivity and reduced glucose uptake. Glucose transporters GLUT1 and
      GLUT4 facilitate glucose uptake across cardiac plasma membranes, and hexokinase
      II (HKII) is the predominant hexokinase isoform in adult cardiac tissue. We
      therefore hypothesized that GLUT1, GLUT4 and HKII gene expression would be
      reduced in heart muscle of growth-retarded rats, and that reduced gene expression
      would result in reduced myocardial glucose uptake. To prove this hypothesis, we
      measured cardiac GLUT1 and GLUT4 mRNA and protein in control IUGR rat hearts at
      day 21 and at day 120 of life. HKII mRNA quantification and 2-deoxyglucose-uptake
      studies were performed in day-120 control and IUGR cardiac muscle. Both GLUT1 and
      GLUT4 mRNA and protein were significantly reduced at day 21 and at day 120 of
      life in IUGR hearts. HKII mRNA was also reduced at day 120. Similarly, both basal
      and insulin-stimulated glucose uptake were significantly reduced in day-120 IUGR
      cardiac muscle. We conclude that adult rats showing IUGR as a result of
      uteroplacental insufficiency express significantly less cardiac GLUT1 and GLUT4
      mRNA and protein than control animals (which underwent sham operations), and that
      this decrease in gene expression occurs in parallel with reduced myocardial
      glucose uptake. We speculate that this reduced GLUT gene expression and glucose
      uptake contribute towards mortality from ischemic heart disease seen in adults
      born with IUGR.

PMID- 11312154
TI  - Effects of adenosine 5'-triphosphate and growth hormone on cellular H+ transport
      and calcium ion concentrations in cloned bovine mammary epithelial cells.
AB  - The present experiment was carried out to investigate the effects of exogenous
      adenosine 5'-triphosphate (ATP) and growth hormone (GH) on cellular H(+) efflux
      rate (extracellular acidification rate) and Ca(2+) concentration ([Ca(2+)](c)) in
      cloned bovine mammary epithelial cells (bMEC) raised from the mammary gland of a
      26-day-pregnant Holstein heifer. Perifusion of 2-day cultured cells with a medium
      containing ATP (10, 100 and 1000 micromol/l) for 30 min caused a significant and
      concentration-dependent increase in the cellular H(+) efflux rate. ATP
      application (100 micromol/l) caused a transient and large increase in [Ca(2+)](c)
      in all cells. In contrast, perifusion with a medium containing bovine GH at 10,
      50 and 250 ng/ml for 30 min caused a significant decrease in the cellular H(+)
      efflux rate in a concentration-dependent manner. However, bovine GH application
      (50 ng/ml) caused a small decrease followed by an increase, in some cases, in
      [Ca(2+)](c). In bMEC treated with lactogenic hormones (1 microgram/l prolactin, 1
      nmol/ml dexamethasone and 5 microgram/ml insulin) for 2 days, the increased H(+)
      efflux rate induced by ATP was significantly reduced, whereas the negative
      response induced by GH was inversely and significantly changed to the positive.
      Treatment of the cells with lactogenic hormones reduced the increase in
      [Ca(2+)](c) induced by ATP stimulation, while it enhanced the increase in
      [Ca(2+)](c) induced by GH stimulation. Application of ATP or GH did not cause any
      significant changes in [pH](c). Treatment with lactogenic hormones enhanced GH
      receptor (GHR) transcription that was determined by RT-PCR. From these results,
      we conclude that exogenous application of ATP and GH causes prompt and
      significant responses in H(+) transport and [Ca(2+)](c) that were significantly
      changed in the opposite direction by the treatment with lactogenic hormones. The
      lactogenic hormone treatment also enhanced GHR transcription, which may change
      post-receptor signal transduction systems for both agents in the bMEC.

PMID- 11312155
TI  - GH gene expression in the submaxillary gland in normal and Ames dwarf mice.
AB  - High local GH-releasing hormone (GHRH) levels are capable of inducing
      transdifferentiation in salivary cells to synthesize GH. However, the factors
      implicated in this process remain unknown. To study this subject, normal and Ames
      dwarf mice were implanted in the submaxillary gland with a slow release pellet
      releasing 21 microgram GHRH (1-29)-NH(2)/day for 2 months. Control animals
      received placebo pellets at the same site. After 60 days, heart blood was
      collected and submaxillary glands were removed. Circulating levels of GH and IGF
      I were significantly decreased (P<0.05) in dwarf mice in comparison with
      controls, and GHRH treatment did not modify either of these two parameters.
      Controls carrying GHRH pellets showed a significantly higher GH content (P<0.05)
      in the submaxillary gland than the placebo-treated normal mice. There were no
      differences between the IGF-I concentrations of placebo- and GHRH-treated
      salivary tissue from normal mice. Analysis of GH mRNA by RT-PCR followed by
      Southern blot revealed that GH transcripts were present in the salivary gland
      samples carrying the placebo pellets in both normal and dwarf mice. The
      expression of GH was significantly (P<0.05) increased by the GHRH pellets in
      salivary tissue from normal mice, but not in submaxillary glands from dwarf mice.
      Pit-1 mRNA was not detected in the GHRH-treated glands of normal and dwarf mice
      by RT-PCR or by Southern blot. Using these highly sensitive methods, we have been
      able to detect the transcription of both GH and Pit-1 in pituitaries from Pit-1
      deficient Ames dwarf mice. The present experiment demonstrates that salivary
      tissue synthesizes GH when it is exposed to the influence of GHRH. Both basal and
      GHRH-induced salivary GH expression appear to be independent of Pit-1.

PMID- 11312156
TI  - Shedding of growth hormone-binding protein is inhibited by hydroxamic acid-based
      protease inhibitors: proposed mechanism of activation of growth hormone-binding
      protein secretase.
AB  - The present study describes events postulated to be involved in the regulated
      mechanism of proteolytic shedding of growth hormone (GH)-binding protein (GHBP).
      Using Chinese hamster ovary (CHO) cell lines stably transfected either with the
      full-length human GH receptor (hGHR) or with the cytoplasmic domain-truncated
      hGHR (hGHR(tr)), we show that the phorbol ester, phorbol 12-myristate 13-acetate
      (PMA), caused a rapid time- and dose-dependent increase in GHBP secretion, which,
      as expected, was matched by a corresponding decrease in cell-surface GHR.
      Furthermore, PMA equally enhanced GHBP release from CHO/hGHR(tr) cells,
      suggesting that the cytoplasmic domain of hGHR is not essential for PMA-induced
      shedding. PMA is known to specifically activate protein kinase C and, indeed, the
      stimulatory effects of PMA in both cell lines were completely inhibited by the
      protein kinase inhibitor, staurosporine (100 nM), suggesting that activation of
      protein kinase C (PKC) may mediate PMA-induced GHBP shedding. Since proteolytic
      cleavage of several cell-surface proteins was shown to be stimulated by
      modulators of PKC activity and inhibited by metalloprotease inhibitors, we
      studied the effects of two hydroxamic acid-based inhibitors of zinc-dependent
      metalloproteases, BB-3103 and Ro31-9790, on GHBP proteolysis. Pretreatment of
      CHO/hGHR cells with both these inhibitors reduced PMA-enhanced shedding of GHBP,
      in a dose-dependent manner, with IC(50) values of approximately 0.41 microM for
      BB-3103 and approximately 0.97 microM for Ro31-9790. In addition, these
      inhibitors dose-dependently reduced the shedding enhanced by the sulfhydryl
      alkylator, N-ethylmaleimide (NEM), with IC(50) values of approximately 0.32
      microM and approximately 0.58 microM for BB-3103 and Ro31-9790 respectively. It
      was of interest to find out that Ro31-9790 acted not only to modulate PMA- or NEM
      induced shedding processes, but also markedly reduced the spontaneous, time
      dependent accumulation of GHBP released from CHO/hGHR cells growing in serum
      containing medium. Taken together, these results suggest that one or more zinc
      dependent metalloprotease(s), acting at the cell surface, may be involved in GHBP
      secretase activity. A scheme is proposed whereby at least part of the regulated
      maturation and/or activation of the protease activity may involve a cysteine
      switch mechanism and/or PKC-dependent phosphorylation. In the long run, specific
      inhibitors of these processes could be applied in the regulation of GHBP levels
      and, thus, of GH availability and/or activity.

PMID- 11312157
TI  - Differential expression of suppressors of cytokine signalling genes in response
      to nutrition and growth hormone in the septic rat.
AB  - GH treatment during critical illness and sepsis may increase mortality. A family
      of negative regulators of cytokine signalling, the suppressors of cytokine
      signalling (SOCS), have been characterised. SOCS provide a mechanism for cross
      talk between the cytokine receptors, including GH. Here, we have investigated the
      impact of nutrition and GH treatment on GH receptor, SOCS1, SOCS-2, SOCS-3 and
      cytokine-inducible SH2-containing protein (CIS) hepatic mRNA expression in a rat
      model of sepsis, caecal ligation and puncture (CLP). Four groups of rats were
      studied: control (food given ad libitum, n=7), CLP only (n=8), CLP and total
      parenteral nutrition (TPN) (n=9), and CLP, TPN and GH (n=10). CLP rats underwent
      surgery and 18 h later received saline or TPN or TPN+GH for 6 h before they were
      killed. Serum IGF-I levels were lower in all CLP groups (P<0.001). The
      combination of TPN and GH treatment increased IGF-I levels compared with the
      saline-treated CLP rats (P<0.01), but IGF-I levels remained lower than control
      animals (P<0.001). GH receptor and GH-binding protein expression in liver was
      reduced in animals subjected to CLP and was unaffected by nutrition or GH
      treatment. Hepatic SOCS-1 was detectable in normal rats, induced in all CLP
      animals but was unaffected by nutrition and GH. Hepatic SOCS-2 expression was
      difficult to detect in normal and CLP rats but was greatly induced in CLP rats
      treated with GH. Hepatic SOCS-3 expression was only just detectable in the
      control group but was elevated in all CLP groups and unaffected by nutrition and
      GH. Hepatic CIS expression was difficult to detect in normal rats, was not
      induced by CLP but was induced by both nutrition and GH. In conclusion, CLP
      induced low IGF-I levels associated with increased expression of SOCS-1 and SOCS
      3, both of which are known to inhibit GH receptor signalling. GH induced SOCS-2
      and CIS in the CLP rat despite resistance with respect to IGF-I generation, and
      parenteral feeding induced CIS in the CLP rat. Thus, there is potential for a
      complex interaction between GH and cytokine signalling at the level of SOCS
      expression whereby the inflammatory response may alter GH signalling and GH may
      influence the inflammatory response.

PMID- 11312158
TI  - Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines.
AB  - Zinc at concentrations of 150, microM or higher induced necrosis as well as
      apoptosis in thyroid cancer cell lines. Necrosis was induced by zinc in a dose
      dependent manner, whereas apoptosis did not increase at higher concentrations of
      zinc. The expression of the antiapoptotic protein phosphorylated Bad was markedly
      increased, whereas the expression of the proapoptotic proteins Bax and Bad
      decreased following Zn(2+) exposure. Zn(2+) induced rapid degradation of IkappaB,
      and an increase in the binding of nuclear transcription factor-kappaB (NF
      kappaB). These observations indicate that antiapoptotic pathways were activated
      in thyroid cancer cells following exposure to Zn(2+). This may be a self-defence
      mechanism against apoptosis and may underlie the general resistance of thyroid
      cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic agent for
      the treatment of thyroid cancer.

PMID- 11312159
TI  - The Booroola (FecB) phenotype is associated with a mutation in the bone
      morphogenetic receptor type 1 B (BMPR1B) gene.
AB  - Genetic variations in ovulation rate which occur in different breeds of sheep
      provide useful models to explore the mechanisms regulating the development of
      antral follicles. The Booroola gene, an autosomal mutation that affects ovulation
      rate, has been known for over two decades and despite intensive research it has
      not yet been identified. Using resources from human genome mapping and known data
      about gene linkage and chromosome location in the sheep, we selected the gene
      encoding the Bone Morphogenetic Protein receptor (BMPR) type 1 B (ALK-6) as a
      candidate site for the mutation. The BMPR1B gene in the human is located at the
      region linked with the Booroola mutation, syntenic to chromosome 6 in the sheep.
      A fragment of the sheep BMPR1B gene was cloned from an ovarian cDNA and the
      deduced aminoacid (AA) sequence is over 98% homologous to the known mammalian
      sequences. cDNA and genomic DNA from 20 Booroola genotypes were screened and two
      point mutation were found in the kinase domain of the receptor, one at base 746
      of the coding region (A in the ++ to a G in FF animals) which results in a change
      from a glutamine in the wild type to a arginine in the Booroola animals. Another
      point mutation was identified at position 1113, (C to A) but this mutation does
      not change the coding aminoacid. The first mutation was confirmed in genomic DNA
      from 10 ewes from an independent Brazilian flock which segregates the Booroola
      phenotype. In all instances homozygous FecB gene carrier (n=11) had only the 746
      A to G mutation, non gene carriers (n=14) had only the wild type sequence and
      heterozygote gene carriers (n=5) had both sequences. This mutation in the
      subdomain 3 of the kinase domain could result in an alteration in the expression
      and/or phosphorylation of SMADs, resulting in the phenotype characteristic of the
      Booroola animals which is the 'precocious' development of a large number of small
      antral follicles resulting in increased ovulation rate.

PMID- 11312160
TI  - Dot size, lead time, and other such clever cognomen: the use of catch phrases.

PMID- 11312162
TI  - CT of bowel wall thickening: significance and pitfalls of interpretation.

PMID- 11312163
TI  - Abdominal radiography after CT reveals urinary calculi: a method to predict
      usefulness of abdominal radiography on the basis of size and CT attenuation of
      calculi.
AB  - OBJECTIVE: The purpose of this study was to determine if the radiographic
      visibility of urinary tract calculi could be predicted on the basis of CT
      features. MATERIALS AND METHODS: The images of 26 patients whose urinary tract
      calculi were revealed on unenhanced helical CT and who also underwent digital
      abdominal radiography were retrospectively reviewed. CT features studied included
      size and CT attenuation of the calculi. These CT findings were correlated with
      the ability to detect the same calculi with radiography. RESULTS: Forty-nine
      urinary tract calculi were detected with unenhanced helical CT in 26 patients.
      Twenty-six (53%) calculi were visible on radiography. Most (79%) calculi larger
      than 5 mm were detectable with radiography (p < 0.01). One (8%) of 13 calculi
      with CT attenuation below 200 H was detectable on radiographs. Ninety-five
      percent (21/22) of calculi with CT attenuation exceeding 300 H were visible on
      radiographs (p < 0.0001). The one remaining calculus was obscured by overlying
      anatomy. CONCLUSION: Radiographic surveillance of urinary tract calculi detected
      with CT may not be useful if the calculi have a CT attenuation below 200 H. Most
      calculi larger than 5 mm and nearly all calculi with a CT attenuation exceeding
      300 H can be seen on abdominal radiographs.

PMID- 11312164
TI  - Dot size, lead time, fallibility, and impact on survival: continuing
      controversies in mammography.

PMID- 11312165
TI  - The missed breast cancer redux: time for educating the public about the
      limitations of mammography?

PMID- 11312166
TI  - Common terminology for single and multislice helical CT.

PMID- 11312168
TI  - Lead arthropathy and systemic lead poisoning from an intraarticular bullet.

PMID- 11312167
TI  - Association of posterior tibial tendon injury with spring ligament injury, sinus
      tarsi abnormality, and plantar fasciitis on MR imaging.
AB  - OBJECTIVE: The purpose of this study was to investigate the frequency of
      abnormalities of the spring ligament, sinus tarsi, and plantar fascia revealed on
      MR imaging in a group of patients with advanced injury of the posterior tibial
      tendon. MATERIALS AND METHODS; MR images from 25 patients with advanced posterior
      tibial tendon injury were retrospectively examined for spring ligament, sinus
      tarsi, and plantar fascia abnormalities. These images were randomly compared with
      those obtained from 25 control patients with normal-appearing posterior tibial
      tendons. RESULTS: The spring ligament was abnormal in 23 (92%) of 25 patients
      with a posterior tibial tendon injury and seven (28%) of 25 patients with a
      normal posterior tibial tendon (p < 0.0001). The sinus tarsi was abnormal in 18
      (72%) of 25 patients with posterior tibial tendon injury and nine (36%) of 25
      patients with a normal posterior tibial tendon (p < 0.0132). The plantar fascia
      was abnormal in seven (32%) of 22 patients with posterior tibial tendon injury
      and two (9%) of 22 patients with a normal posterior tibial tendon (p < 0.0768).
      Two or more associated abnormalities were present in 20 (80%) of 25 patients with
      posterior tibial tendon injury and four (16%) of 25 patients with a normal
      posterior tibial tendon (p < 0.0001). CONCLUSION: Advanced posterior tibial
      tendon injury has a high association with spring ligament and sinus tarsi
      abnormalities on MR imaging. There was a low association between advanced
      posterior tibial tendon injury and plantar fascia abnormality. Patients with
      posterior tibial tendon injury often have abnormalities of two or more associated
      structures.

PMID- 11312169
TI  - MR imaging findings of entrapment of the flexor hallucis longus tendon.
AB  - OBJECTIVE: In this retrospective study, we describe the MR imaging patterns of
      various causes of flexor hallucis longus tendon entrapment. CONCLUSION:
      Entrapment of the flexor hallucis longus tendon may be due to an enlarged os
      trigonumtarsitarsi, calcaneal fracture, and soft-tissue scar. These disorders
      have characteristic imaging findings that may be revealed on MR imaging.

PMID- 11312170
TI  - Subtendinous bone marrow edema patterns on MR images of the ankle: association
      with symptoms and tendinopathy.
AB  - OBJECTIVE: We sought to describe a pattern of subtendinous bone marrow edema on
      MR images of the ankle and to determine if there is an association with location
      of symptoms and overlying tendinopathy. MATERIALS AND METHODS: At 1.5 T, 141 MR
      examinations of the ankle (116 clinical examinations of patients with chronic
      pain, 25 of asymptomatic control patients) were performed using T1-weighted,
      proton density-weighted fast spin-echo, and T2-weighted fat-suppressed fast spin
      echo sequences. Images were retrospectively reviewed by two musculoskeletal
      radiologists for presence of bone marrow edema occurring in a subcortical
      location associated with the course of the medial or lateral tendon groups, as
      well as focal thickening or increased T2 signal within the tendons. These
      findings were correlated with clinical information regarding symptom location.
      The association of subtendinous marrow edema with tendinopathy and symptom
      location was statistically analyzed. RESULTS: Subtendinous bone marrow edema was
      present at 26 sites on 24 ankle MR examinations (17%) (at the medial malleolus [n
      = 17] associated with the posterior tibialis tendon, at the lateral malleolus [n
      = 6] and the calcaneus [n = 2] associated with the peroneus longus and brevis
      tendons, and at the cuboid [n = 1] associated with the peroneus longus tendon).
      These subtendinous bone marrow edema patterns were significantly associated with
      overlying tendon abnormality medially (p = 0.001) and laterally (p = 0.001), and
      with symptoms medially (p = 0.0016) but not laterally (p = 0.078). CONCLUSION: On
      MR images of the ankle, bone marrow edema localized in a subtendinous location is
      associated with overlying tendinopathy medially and laterally and with ankle pain
      medially.

PMID- 11312171
TI  - Sonography and radiography of soft-tissue foreign bodies.

PMID- 11312172
TI  - Primary non-Hodgkin's lymphoma of the femur.

PMID- 11312173
TI  - The vacuum phenomenon: a CT sign of nonunited fracture.
AB  - OBJECTIVE: The purpose of this study was to describe on CT scans the presence of
      a gas collection within a bone fracture reflecting the vacuum phenomenon as a
      sign of nonunited fracture. CONCLUSION: A gas collection between fractured bone
      fragments suggests a nonunited fracture.

PMID- 11312174
TI  - Ossifying muscle metastases from an esophageal adenocarcinoma mimicking myositis
      ossificans.

PMID- 11312175
TI  - Unenhanced CT findings of vascular compromise in association with
      intussusceptions in adults.
AB  - OBJECTIVE: The purpose of this study was to evaluate unenhanced CT findings for
      predicting the degree of vascular compromise in intussusception observed at
      surgery. MATERIALS AND METHODS: The imaging studies, clinical records, and
      surgical and pathologic findings in 25 patients with intussusception were
      reviewed retrospectively. We evaluated six CT findings based on the abnormalities
      of each component of intussusception. Presence or absence of these findings was
      compared with the degree of vascular compromise as observed on pathologic
      examination, such as edema, ischemia, or necrosis. RESULTS: The hypodense layer
      was observed in 16 of 18 intussusceptions with various degrees of vascular
      compromise. A fluid collection surrounded by the returning wall, which was
      revealed to correspond to trapped peritoneal fluid, was observed in eight of nine
      intussusceptions with ischemia or necrosis. A gas collection surrounded by the
      returning wall was observed in two of four intussusceptions with necrosis. Free
      peritoneal fluid coexisted with a fluid collection surrounded by the returning
      wall in all the intussusceptions except one. Bowel obstruction was observed in
      six of nine intussusceptions with ischemia or necrosis. The maximum wall
      thickness was not related to the degree of vascular compromise. CONCLUSION: The
      CT findings of a hypodense layer in the returning wall, fluid collection in the
      space surrounded by the returning wall, and gas collection in the space
      surrounded by the returning wall can be useful in predicting the degree of
      vascular compromise in intussusception.

PMID- 11312177
TI  - Short-segment Barrett's esophagus: findings on double-contrast esophagography in
      20 patients.
AB  - OBJECTIVE: The purpose of this study was to determine the findings of short
      segment Barrett's esophagus on double-contrast esophagography. MATERIALS AND
      METHODS: A review of pathology and endoscopy data revealed 142 patients with
      short-segment Barrett's esophagus, which was defined as columnar epithelium in
      the distal esophagus extending 3 cm or less above the gastroesophageal junction
      at endoscopy with histopathologic confirmation of intestinal metaplasia. Twenty
      of these patients underwent double-contrast esophagography. These 20 patients
      comprised our study group. The original radiology reports and images were
      reviewed to determine the findings on double-contrast esophagography. Medical
      records were also reviewed to determine the clinical findings and treatment.
      RESULTS: Double-contrast esophagrams revealed hiatal hernias in 18 patients
      (90%), gastroesophageal reflux in 16 (80%), reflux esophagitis in seven (35%),
      peptic scarring or strictures in 11 (55%), and a reticular mucosal pattern in
      none. A total of 14 patients (70%) had morphologic findings of reflux disease
      with esophagitis alone (three patients), peptic scarring or strictures alone
      (seven patients), or both (four patients), but the remaining six (30%) had hiatal
      hernias or gastroesophageal reflux as the only radiographic finding. CONCLUSION:
      Double-contrast esophagography revealed morphologic findings of reflux disease
      with esophagitis, peptic scarring or strictures, or both in 70% of patients with
      short-segment Barrett's esophagus. Thus, the absence of esophagitis or peptic
      scarring or strictures on double-contrast esophagography does not exclude the
      possibility of short-segment Barrett's esophagus.

PMID- 11312178
TI  - Congenital esophageal stenosis in adults: clinical and radiographic findings in
      seven patients.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical and
      radiographic findings in seven adults with congenital esophageal stenosis.
      CONCLUSION: In young or middle-aged individuals, particularly men with long
      standing dysphagia, an upper or mid esophageal stricture with multiple ringlike
      constrictions is a characteristic appearance of congenital esophageal stenosis on
      double-contrast esophagography.

PMID- 11312179
TI  - Mr cholangiography with volume rendering: receiver operating characteristic curve
      analysis in patients with choledocholithiasis.
AB  - OBJECTIVE: The purpose of our study was to compare observer performances for the
      diagnosis of choledocholithiasis using MR cholangiography with volume-rendered,
      maximum-intensity-projection, and thick-section half-Fourier rapid acquisition
      with relaxation enhancement sequences. MATERIALS AND METHODS: The images from
      three types of MR cholangiography performed on 43 patients with biliary calculi
      were retrospectively analyzed. Image review was conducted for two anatomic
      compartments (upper biliary tract and common bile duct). A total of 86
      compartments, including 19 with bile duct calculi, were reviewed by three
      independent off-site gastrointestinal radiologists. Observer performance was
      determined by receiver operating characteristic curve analysis. Image quality was
      subjectively judged by three radiologists. RESULTS: Sensitivity was higher with
      volume-rendered MR cholangiography (58%) than with thick-section (54%, not
      significant) and maximum-intensity-projection MR cholangiography (47%, p < 0.07).
      Specificity was higher with volume-rendered MR cholangiography (92%) than with
      thick-section (86%, p < 0.03) and maximum-intensity-projection MR cholangiography
      (88%, not significant). Accuracy was higher with volume-rendered MR
      cholangiography (84%) than with thick-section and maximum-intensity-projection MR
      cholangiography (79% for both, not significant). Observer performance with volume
      rendered MR cholangiography (A(z) = 0.791--0.952) was better than that with thick
      section (A(z) = 0.722--0.834) and maximum-intensity-projection MR cholangiography
      (A(z) = 0.771--0.887). Image quality was better with maximum-intensity-projection
      MR cholangiography and thick-section MR cholangiography than with volume-rendered
      MR cholangiography (p < 0.0001). CONCLUSION: Observer performance with volume
      rendered MR cholangiography was better than that with maximum-intensity
      projection and thick-section MR cholangiography for the diagnosis of
      choledocholithiasis. Volume rendering may be an efficient technique for the
      reconstruction of MR cholangiography.

PMID- 11312180
TI  - Phase-inversion sonography during the liver-specific late phase of contrast
      enhancement: improved detection of liver metastases.
AB  - OBJECTIVE: The purpose of our study was to assess whether phase-inversion
      sonography during the late, liver-specific phase of contrast enhancement using
      Levovist improves the detection of hepatic metastases relative to unenhanced
      conventional B-mode sonography. SUBJECTS AND METHODS: Sixty-two patients were
      studied with unenhanced B-mode sonography and phase-inversion sonography 2.5 min
      after the injection of Levovist. All patients underwent one reference examination
      (CT, MR imaging, or intraoperative sonography). The conspicuity, number, size,
      and distribution of metastases before and after contrast administration as judged
      by a sonographer (who was unaware of other imaging findings) were compared with
      each other and with reference imaging. RESULTS: The conspicuity of metastases was
      improved by contrast-enhanced phase inversion in 94% of patients. Thirty-nine
      patients showed metastases on reference imaging; 36 of these were positive on
      baseline sonography and 38 on phase-inversion sonography. Phase-inversion
      sonography showed more reference imaging-confirmed metastases than baseline
      sonography in 28 patients (45%). The average number of confirmed metastases per
      patient was 3.06 for baseline sonography and 5.42 for contrast-enhanced phase
      inversion sonography (p < 0.01). The average sensitivity for detecting individual
      metastases improved from 63% to 91%. Metastases of less than 1 cm were shown in
      14 patients on baseline sonography, in 24 patients on phase-inversion sonography,
      and in 26 on reference imaging. Both sonographic techniques showed false-positive
      lesions in six patients. CONCLUSION: Contrast-enhanced phase-inversion sonography
      in the liver-specific phase of contrast enhancement using Levovist provides a
      marked improvement in the detection of hepatic metastases relative to unenhanced
      conventional sonography, without loss of specificity. Phase-inversion sonography
      was particularly advantageous in detecting small metastases and may be a
      competitive alternative to CT and MR imaging.

PMID- 11312181
TI  - Using contrast-enhanced sonography to assess the effectiveness of transcatheter
      arterial embolization for hepatocellular carcinoma.
AB  - OBJECTIVE: We evaluated the usefulness of contrast-enhanced wideband harmonic
      gray-scale sonography in assessing the therapeutic effects of transcatheter
      arterial embolization for patients with hepatocellular carcinoma and compared the
      findings of this imaging modality with those of helical CT. SUBJECTS AND METHODS:
      Twenty-nine patients with 39 hepatocellular carcinoma lesions were examined. We
      scanned lesions before and after therapy using contrast-enhanced wideband
      harmonic gray-scale sonography after injection of a galactose-palmitic acid
      contrast agent. All patients held their breath for 20--50 sec after injection
      while the vascularity of the tumor was observed. We then monitored tumor
      enhancement between 60 and 180 sec after injection with patients breath-holding
      for a few seconds. Lesions were considered to exhibit viable tumor residue if
      hypervascular enhancement was observed in the tumor. We compared this enhancement
      with helical CT findings. RESULTS: After therapy, 36 of the 39 lesions showed
      viable tumor residue on contrast-enhanced wideband harmonic gray-scale
      sonography, with no artifacts from iodized oil. Helical CT revealed a high
      attenuation area in 12 of the 36 lesions, whereas 24 of the 36 lesions could not
      be evaluated for tumor residue as a result of artifacts from iodized oil
      accumulation in the tumor. The remaining three lesions showed complete deposition
      of iodized oil and complete necrosis on contrast-enhanced wideband harmonic gray
      scale sonography. CONCLUSION: Contrast-enhanced wideband harmonic gray-scale
      sonography is useful in evaluating the therapeutic effects of transcatheter
      arterial embolization for hepatocellular carcinoma.

PMID- 11312183
TI  - Echinococcus multilocularis revisited.

PMID- 11312184
TI  - Assessment of gadolinium-enhanced time-resolved three-dimensional MR angiography
      for evaluating renal artery stenosis.
AB  - OBJECTIVE: The purpose of this study was to assess the image quality of
      gadolinium-enhanced time-resolved three-dimensional (3D) MR angiography and to
      evaluate its accuracy in revealing renal artery stenosis. SUBJECTS AND METHODS:
      Thirty-nine patients underwent MR angiography using an ultrafast 3D Fourier
      transform spoiled gradient-recalled acquisition in the steady state (TR/TE range,
      2.6/0.7--0.8). Five seconds after administration of 15--20 mL gadodiamide
      hydrate, four or five consecutive data sets with imaging times of 7.0--7.6 sec
      were acquired during a single breath-hold. A timing examination was not
      performed. Image quality was assessed using quantitative analysis (signal-to
      noise, contrast-to-noise, and venous-to-arterial enhancement ratios) and
      qualitative analysis (presence of venous overlap, presence of artifacts, and
      degree of renal arterial enhancement). MR angiography depiction of the renal
      artery stenosis was evaluated using conventional angiography as the standard of
      reference. RESULTS: On the best arterial phase, average aortic signal-to-noise
      ratio (+/-SD) was 74.5 +/- 24.4, aorta-to--inferior vena cava contrast-to-noise
      ratio was 70.8 +/- 23.4, and inferior vena cava--to-aorta venous-to-arterial
      enhancement ratio was 0.03 +/- 0.04. No venous overlap was seen in 38 of 39
      patients. Substantial enhancement of renal arteries was seen in all patients
      without any noticeable artifacts. MR angiography correctly depicted the degree of
      stenosis in 44 of 47 normal arteries, 13 of 16 mildly stenotic arteries, five of
      five moderately stenotic arteries, three of four severely stenotic arteries, and
      one of one occluded artery. Sensitivity and specificity for revealing greater
      than 50% stenosis was 100%. CONCLUSION: Time-resolved 3D MR angiography can
      provide high-quality arteriograms. Its performance in revealing renal artery
      stenosis is comparable with that of conventional angiography.

PMID- 11312185
TI  - Using gadolinium-infusion MR venography to show the impalpable testis in
      pediatric patients.
AB  - OBJECTIVE; This study evaluated the adjunctive value of gadolinium-infusion MR
      venography to locate the impalpable testis. SUBJECTS AND METHODS: Routine MR
      imaging and MR venography were performed in 34 patients presenting with
      impalpable testis. MR venography was performed by dynamic injection of
      gadopentetate dimeglumine bismethylamide with images taken at delayed venous
      phases. The site of the testis was determined by detection of the contrast
      enhanced pampiniform venous plexus. RESULTS: A total of 44 impalpable testes were
      examined. Twenty-six hypoplastic canalicular testes, two testes at pelvic
      skinfold, four atrophic testes in the scrotum, and five intraabdominal testes
      were detected on both routine MR imaging and MR venography. Five "vanishing"
      testes in the scrotum and two at the groin region were detected by MR venography
      but not on MR imaging. CONCLUSION: Gadolinium-infusion MR venography is superior
      to MR imaging in the detection of atrophic testes. The method is a useful adjunct
      in patients with negative MR imaging findings.

PMID- 11312186
TI  - MR Imaging of sports-related pseudotumor in children: mid femoral diaphyseal
      periostitis at insertion site of adductor musculature.
AB  - OBJECTIVE: The objective of this study was to review the imaging appearance of
      the femurs of five patients who had been referred from outside institutions after
      presenting with thigh pain and being given a preliminary diagnosis of primary
      malignant bone tumor. Typically, when making a diagnosis, physicians place
      emphasis on the characteristic appearances of diseases on MR imaging, but such
      appearances may be misleading. An awareness of the specific MR imaging pattern of
      stress-related partial muscle avulsion can lead to the correct diagnosis.
      CONCLUSION: Femoral diaphyseal periostitis after a sports injury to the adductor
      musculature in children has a characteristic imaging appearance. This condition
      can initially appear to be misleadingly aggressive. Knowledge of the findings
      particularly of the findings on MR imaging-in the proper clinical setting can
      help physicians make the correct diagnosis and eliminate unnecessary biopsy or
      inappropriate treatment.

PMID- 11312187
TI  - Cross-sectional imaging of abnormalities of the abdominal wall in pediatric
      patients.

PMID- 11312188
TI  - Rates and causes of disagreement in interpretation of full-field digital
      mammography and film-screen mammography in a diagnostic setting.
AB  - OBJECTIVE: This study was performed to determine the rates and causes of
      disagreements in interpretation between full-field digital mammography and film
      screen mammography in a diagnostic setting. SUBJECTS AND METHODS: Patients
      undergoing diagnostic mammography were invited to participate in the digital
      mammography study. Three views, selected by the radiologist interpreting the film
      screen mammography, were obtained in both film-screen mammography and digital
      mammography. Radiologists independently assigned a Breast Imaging Reporting and
      Data System (BI-RADS) category to the film-screen mammography and the digital
      mammography images. The BI-RADS categories were grouped into the general
      categories of agreement, partial agreement, or disagreement. A third and
      different radiologist reviewed all cases of disagreement, reached a decision as
      to management, and determined the primary cause of disagreement. RESULTS: Six
      radiologists reviewed digital mammography and film-screen mammography diagnostic
      images in a total of 1147 breasts in 692 patients. Agreement between digital
      mammography and final film-screen mammography assessment was present in 937
      breasts (82%), partial agreement in 159 (14%), and disagreement in 51 (4%), for a
      kappa value of 0.29. The primary causes of disagreement were differences in
      management approach of the radiologists (52%), information derived from
      sonography or additional film-screen mammograms (34%), and technical differences
      between the two mammographic techniques (10%). CONCLUSION: Significant
      disagreement between film-screen mammography and digital mammography affecting
      follow-up management was present in only 4% of breasts. The most frequent cause
      of disagreement in interpretation was a difference in management approach between
      radiologists (interobserver variability). This source of variability was larger
      than that due to differences in lesion visibility between film-screen mammography
      and digital mammography.

PMID- 11312189
TI  - Incidental enhancing lesions found on MR imaging of the breast.
AB  - OBJECTIVE: This study was undertaken to determine the frequency and significance
      of foci of enhancement having no corresponding mammographic or clinical
      abnormality that are encountered on MR imaging of the breast performed to
      evaluate mammograms with equivocal findings. MATERIALS AND METHODS: Reports from
      MR examinations of 103 patients who underwent MR imaging of the breast to
      evaluate questionable mammographic findings were retrospectively reviewed. We
      identified cases that had focal enhancing lesions without a corresponding
      mammographic or palpable abnormality. Clinical history, mammograms, MR images,
      and follow-up information were reviewed. RESULTS: Of the 103 patients, 30 (29%)
      had incidental foci of enhancement. These women were significantly younger, more
      often premenopausal, and more likely to have dense breasts than those who did not
      have incidental foci. Tissue confirmation of the incidental foci was available
      for seven patients, mammographic follow-up was available for a mean interval of
      22 months for 22 patients, and no follow-up was available for one. Cancer at the
      incidental sites was diagnosed in one of the 30 patients with multiple foci. She
      was also shown to have cancer at the site originally questioned mammographically
      (index site). None of the remaining patients has had a diagnosis of malignancy at
      the incidental sites. CONCLUSION: Incidental enhancing foci are common in women
      undergoing breast MR imaging for questionable findings on mammography, occurring
      in 29% of our patients. Our results suggest that unless malignancy is diagnosed
      elsewhere in the breast, these incidental foci are unlikely to be malignant.

PMID- 11312190
TI  - Calcifications of lobular carcinoma in situ of the breast: radiologic-pathologic
      correlation.
AB  - OBJECTIVE: Because lobular carcinoma in situ is thought to be an incidental
      finding at breast pathology, the finding of lobular carcinoma in situ at core
      biopsy poses a diagnostic dilemma of radiologic-pathologic concordance. The
      purpose of this article is to describe the radiologic-pathologic correlation of
      calcifications associated with lobular carcinoma in situ of the breast. MATERIALS
      AND METHODS: Between July 1999 and July 2000, seven excisional biopsies resulted
      in findings of lobular carcinoma in situ of mammographic calcifications. The
      radiographic features of the calcifications were characterized by the Breast
      Imaging Reporting and Data System lexicon, and pathologic features were reviewed.
      RESULTS: Two forms of lobular carcinoma in situ were associated with
      calcifications: the classic form with small, uniform cells, and the pleomorphic
      form with larger cells frequently associated with central necrosis. On
      mammography, all calcifications were clustered, punctate, high density, and
      smaller than or equal to 0.5 mm, although mammographically visible calcifications
      found in the pleomorphic type tended to be larger and more dense. Additionally,
      infiltrating lobular carcinoma was found after surgical excision in two (40%) of
      five patients with pleomorphic lobular carcinoma in situ. CONCLUSION:
      Calcifications can be associated with lobular carcinoma in situ and therefore
      concordant at stereotactic core biopsy. The classic form may be incidental and
      clinically innocuous. The pleomorphic form is morphologically similar to ductal
      carcinoma in situ and may have a greater tendency for invasion.

PMID- 11312192
TI  - Artifacts and pitfalls in sonographic imaging of the breast.

PMID- 11312193
TI  - Making the transition: the role of helical CT in the evaluation of potentially
      acute thoracic aortic injuries.
AB  - OBJECTIVE: The purpose of this study was to show that helical CT could be used at
      our center in lieu of routine aortography to examine patients who have had
      serious blunt chest trauma. We also wanted to assess the potential savings of
      using CT to avoid unnecessary aortography. MATERIALS AND METHODS: The
      institutional review board approved the parallel imaging-CT immediately followed
      by aortography-of patients presenting with blunt chest trauma between August 1997
      and August 1998. To screen patients for potential aortic injuries, we performed
      parallel imaging on 142 patients, and these patients comprised our patient
      population. CT examinations of the patients were reviewed for signs of injury by
      radiologists who were unaware of each other's interpretations and the
      aortographic results. Findings of CT examinations were classified as negative,
      positive, or inconclusive for injury. Aortography was performed immediately after
      CT. The technical and professional fees for both transcatheter aortography and
      helical CT were also compared. RESULTS: Our combined kappa value for all CT
      interpretations was 0.714. The aortographic sensitivity and negative predictive
      value were both 100%. Likewise, the sensitivity and negative predictive value of
      CT were 100%. The total costs of performing aortography were estimated at
      approximately $402,900, whereas those for performing helical CT were estimated at
      $202,800. CONCLUSION: Helical CT has a sensitivity and negative predictive value
      equivalent to that of aortography. Using CT to eliminate the possibility of
      mediastinal hematoma and to evaluate the cause of an abnormal aortic contour in a
      trauma patient allows us to use aortography more selectively. Avoiding the
      performance of unnecessary aortography will expedite patient care and reduce
      costs. We report the results of our experience with CT and how our center
      successfully made this transition in the initial examination of patients with
      serious thoracic trauma.

PMID- 11312194
TI  - Using CT to diagnose tracheal rupture.
AB  - OBJECTIVE: A retrospective study was performed to assess CT sensitivity for
      diagnosing tracheal rupture. Intubated cadaver tracheas were examined to assess
      endotracheal tube balloon overdistention and deformity and to evaluate the
      relationship of balloon pressures to tracheal injury. MATERIALS AND METHODS: Neck
      or chest CT scans of 14 patients with tracheal rupture and 41 control trauma
      patients with pneumomediastinum but without tracheal injury were reviewed and
      compared to assess the presence and location of extrapulmonary air, whether
      direct visualization of tracheal wall disruption was possible, the size and shape
      of endotracheal tube balloon, signs of transtracheal balloon herniation in
      intubated patients, and the location of the extratracheal endotracheal tube.
      Intact and experimentally injured cadaver tracheas were used to evaluate tube
      balloon pressure and configuration. RESULTS: All 14 patients with tracheal
      rupture had deep cervical air and pneumomediastinum. Overdistention of the tube
      balloon occurred in 71% (5/7) of the intubated patients, and balloon herniation
      occurred in 29% (2/7). Direct tracheal injury was seen in 71% (10/14) of the
      patients as a wall defect (n = 8) or deformity (n = 2). Overall, CT was 85%
      sensitive for detecting tracheal injury. Patients with tracheal injury had a
      significantly lower incidence of pneumothorax (p = 0.01) than did the control
      group. The CT appearance of balloon herniation through defects in the cadaver
      tracheas closely mimicked those of patients with tracheal injury. The amount of
      balloon pressure required to rupture the intubated trachea was extremely high and
      rupture was difficult to obtain. CONCLUSION: CT can reveal tracheal injury and
      can be used to select trauma patients with pneumomediastinum for bronchoscopy,
      leading to early confirmation and treatment.

PMID- 11312195
TI  - Combined CT venography and pulmonary angiography: how much venous enhancement is
      routinely obtained?
AB  - OBJECTIVE: Combined CT venography and helical pulmonary angiography is a new
      diagnostic test that permits radiologists to check both the pulmonary arteries
      for embolism and the deep veins of the abdomen, pelvis, and legs for thrombosis
      in a single examination. The purpose of this study was to determine the degree of
      venous enhancement routinely obtained using this combined CT examination.
      MATERIALS AND METHODS: We identified all patients at a single institution who,
      during a 29-month period, had symptoms suggestive of pulmonary embolism and who
      underwent CT venography and helical pulmonary angiography. The examinations were
      performed after the patients received a rapid (3--5 mL/sec) IV injection of 150
      mL of nonionic contrast medium (240 mg I/mL). CT venography of the abdomen,
      pelvis, and lower extremities was performed as follows: Beginning 3 min after the
      start of contrast medium infusion for helical CT pulmonary angiography, 1-cm
      axial images obtained at 5-cm intervals were acquired from an area ranging from
      the diaphragm to the calves. Patients who had evidence of deep venous thrombosis
      on CT scans were excluded from further analysis. The venous portions of the
      remaining 429 examinations were retrospectively reviewed at a CT console or
      workstation by one of two radiologists, and Hounsfield unit measurements were
      recorded from the inferior vena cava as well as from the right and left external
      or internal iliac, common femoral, superficial femoral, and popliteal veins. A
      single Hounsfield unit measurement was obtained from the center of each vessel
      using a region of interest that was approximately half the diameter of the
      vessel. Mean Hounsfield unit measurements were then calculated for these venous
      stations. RESULTS: Mean Hounsfield unit measurements at the inferior vena cava
      and at the right and left external or internal iliac veins were 97, 95, and 95 H,
      respectively. Mean measurements at the common femoral veins were 95 H for both
      the right and left; the mean measurements at the superficial femoral veins were
      91 H for both the right and left, and those at the popliteal veins were 97 H for
      the right and 94 H for the left. CONCLUSION: CT venography of the abdomen,
      pelvis, and lower extremities begun 3 min after the start of contrast medium
      infusion for helical CT pulmonary angiography routinely produced high mean levels
      of venous enhancement.

PMID- 11312196
TI  - CT features of pulmonary alveolar proteinosis.
AB  - OBJECTIVE: This investigation describes the CT features of pulmonary alveolar
      proteinosis in a large group of patients. MATERIALS AND METHODS: A retrospective
      review of 139 chest CT scans (79 thick-section scans and 60 thin-section scans)
      from 27 patients with pathologically proven pulmonary alveolar proteinosis was
      performed. Two independent observers assessed the intraslice patterns and zonal
      distribution of disease on three CT images of each lung. The observers also
      graded the percentage of ground-glass opacities, air-space opacities, fibrosis,
      interlobular opacities, intralobular opacities, and emphysema in each slice. CT
      scans obtained before and after lavage related to 12 whole-lung lavage treatments
      on nine patients were evaluated. RESULTS: The dominant intraslice pattern was
      geographic, but a diffuse pattern was sometimes seen. The most common zonal
      pattern was uniform; a lower zone predominance was next most frequent. Ground
      glass, air-space, and fibrotic opacities had a generally homogeneous craniocaudal
      distribution, but there was a trend toward more interlobular opacities at the
      lung bases (p < 0.002). Ground-glass opacities were seen on at least one scan in
      100% of the patients. Interlobular opacities (85%), air-space opacities (78%),
      substantial fibrosis (7%), and intralobular opacities (7%) occurred less
      frequently. Compared with thick-section images, thin-section images showed more
      interlobular opacities, but no difference in ground-glass, air-space, or fibrotic
      disease. The proportion of lung affected by ground-glass and interlobular
      opacities decreased significantly (p < 0.05) after lavage. CONCLUSION: Pulmonary
      alveolar proteinosis does not present only with alveolar disease. The CT
      appearance typically combines different types of opacities with a geographic
      pattern and a uniform zonal distribution with variation over time.

PMID- 11312197
TI  - Coronary artery calcium measurement: agreement of multirow detector and electron
      beam CT.
AB  - OBJECTIVE: The purpose of our study was to establish the most suitable algorithm
      to compare coronary artery calcium measurements performed with electron beam CT
      and multirow detector CT for the assessment of coronary artery disease. SUBJECTS
      AND METHODS: Coronary artery screening was performed in 100 patients with both
      electron beam and multirow detector CT. The images were transferred to a
      dedicated workstation for determination of the calcium score, volume, mass,
      density, and number of lesions. In addition to the traditional threshold of 130
      H, the score of multirow detector CT studies was reevaluated at a threshold of 90
      H. Fifty-nine of the patients underwent conventional coronary catheterization.
      Receiver operating characteristic curve analysis of the different scoring
      algorithms for detection of significant coronary artery stenosis was performed.
      RESULTS: The correlation between electron beam CT and multirow detector CT was
      high for every quantification algorithm. Determination of the score and the
      number of lesions with multirow detector CT revealed a systematic error of the
      measurement compared with electron beam CT. The areas under the curve in the
      receiver operating characteristic curve analyses for electron beam and multirow
      detector CT were similar for the score, volume, and mass, whereas they were lower
      for the density. No significant difference was found for the areas under the
      curve between scores using a 130-H and those using a 90-H threshold. CONCLUSION:
      Volume and mass indexes are superior to the traditional score, density, and
      number of lesions for comparing the results of electron beam and multirow
      detector CT and for determining significant coronary artery disease.

PMID- 11312198
TI  - Three-dimensional contrast-enhanced MR angiography of endovascular covered stents
      in patients with peripheral arterial occlusive disease.
AB  - OBJECTIVE: Three-dimensional contrast-enhanced MR angiography was performed to
      study MR characteristics of Hemobahn devices. MATERIALS AND METHODS: Changes in
      endoluminal signal intensities and the precision of the endoluminal diameter
      measurement were investigated in phantom studies for different concentrations of
      gadopentetate dimeglumine. Before and after the Hemobahn devices had been
      implanted, 10 patients with peripheral arterial occlusive disease were examined
      on MR imaging and three-dimensional contrast-enhanced MR angiography. RESULTS:
      Phantom experiments using three-dimensional MR angiography showed stent-related
      signal void as a dark ring in the axial image orientation, providing a precise
      delineation of the stent--vessel border (mean endoluminal diameter, 8.2 mm; SD,
      0.6 mm). Changes in endoluminal signal intensity were evaluated quantitatively.
      Stent-related artifacts did not compromise diagnostic imaging quality. All
      Hemobahn devices were found to be patent without migration of an implanted graft.
      In one patient, an extensive perigraft reaction (edema and contrast-enhanced
      perivascular tissue) was postinterventionally detected on MR imaging and
      corresponded to clinically evident postimplantation symptoms. CONCLUSION: Three
      dimensional contrast-enhanced MR angiography is a suitable tool to follow up the
      implantation of Hemobahn devices and to detect intra- and extraluminal
      abnormalities.

PMID- 11312200
TI  - Safety of CO(2)- and gadodiamide-enhanced angiography for the evaluation and
      percutaneous treatment of renal artery stenosis in patients with chronic renal
      insufficiency.
AB  - OBJECTIVE: The objective of our study was to evaluate the safety of CO(2) and
      gadodiamide angiography for diagnosing and percutaneously treating renal artery
      stenosis in patients with chronic renal insufficiency and presumed ischemic
      nephropathy. SUBJECTS AND METHODS: One hundred forty-six consecutive patients
      with chronic renal insufficiency (serum creatinine > 1.5 mg/dL) were examined for
      renal artery stenosis using CO(2) and gadodiamide as the angiographic contrast
      agents. If renal artery stenosis was detected, percutaneous balloon angioplasty
      with or without stenting was performed. In patients for whom 48-hr creatinine
      levels were available, we performed an analysis to determine the incidence of
      contrast-involved nephropathy (increase in serum creatinine of 0.5 mg/dL at 48 hr
      without identifiable cause). Major complications were reported up to 1 week, and
      mortality was reported up to 30 days after the procedure. RESULTS: Ninety-five
      patients had serum creatinine levels available at 48 hr. An increase in
      creatinine of greater than 0.5 mg/dL at 48 hr occurred in three patients (3.2%),
      presumably caused by CO(2), by gadodiamide, or by both. Neither diabetes nor the
      degree of preexisting chronic renal insufficiency was a predictor of worsening
      renal function 48 hr after the procedure. The volumes of CO(2) and gadodiamide
      used for diagnostic studies alone versus the volume used for interventional
      studies was not significantly different (for CO(2), p = 0.09; for gadodiamide, p
      = 0.30). Eleven major complications occurred in eight patients (5.5%). Two deaths
      (1.4%) occurred within 30 days. One death was due to cholesterol embolization and
      the other was not believed to be related to the procedure. CONCLUSION:
      Angiography and percutaneous treatment of renal artery stenosis in patients with
      chronic renal insufficiency and suspected ischemic nephropathy can be performed
      relatively safely using CO(2) and gadodiamide as angiographic contrast agents
      without an increased risk of complications. Contrast-induced nephropathy
      potentially occurred in 3.2% of patients. Neither the degree of underlying renal
      insufficiency nor diabetes was a risk factor for predicting a greater likelihood
      of renal function worsening at 48 hr of follow-up. The volumes of CO(2) and
      gadodiamide used in this study did not result in an increased risk of contrast
      involved nephropathy.

PMID- 11312201
TI  - Accuracy for detection of simulated lesions: comparison of fluid-attenuated
      inversion-recovery, proton density--weighted, and T2-weighted synthetic brain MR
      imaging.
AB  - OBJECTIVE: The objective of our study was to determine the effects of MR sequence
      (fluid-attenuated inversion-recovery [FLAIR], proton density--weighted, and T2
      weighted) and of lesion location on sensitivity and specificity of lesion
      detection. MATERIALS AND METHODS: We generated FLAIR, proton density-weighted,
      and T2-weighted brain images with 3-mm lesions using published parameters for
      acute multiple sclerosis plaques. Each image contained from zero to five lesions
      that were distributed among cortical-subcortical, periventricular, and deep white
      matter regions; on either side; and anterior or posterior in position. We
      presented images of 540 lesions, distributed among 2592 image regions, to six
      neuroradiologists. We constructed a contingency table for image regions with
      lesions and another for image regions without lesions (normal). Each table
      included the following: the reviewer's number (1--6); the MR sequence; the side,
      position, and region of the lesion; and the reviewer's response (lesion present
      or absent [normal]). We performed chi-square and log-linear analyses. RESULTS:
      The FLAIR sequence yielded the highest true-positive rates (p < 0.001) and the
      highest true-negative rates (p < 0.001). Regions also differed in reviewers' true
      positive rates (p < 0.001) and true-negative rates (p = 0.002). The true-positive
      rate model generated by log-linear analysis contained an additional sequence
      location interaction. The true-negative rate model generated by log-linear
      analysis confirmed these associations, but no higher order interactions were
      added. CONCLUSION: We developed software with which we can generate brain images
      of a wide range of pulse sequences and that allows us to specify the location,
      size, shape, and intrinsic characteristics of simulated lesions. We found that
      the use of FLAIR sequences increases detection accuracy for cortical-subcortical
      and periventricular lesions over that associated with proton density- and T2
      weighted sequences.

PMID- 11312202
TI  - Primary lymphoma of the central nervous system: typical and atypical CT and MR
      imaging appearances.

PMID- 11312203
TI  - Question and answer. Solid-column single contrast barium enema after failed
      colonoscopy.

PMID- 11312204
TI  - Corpus callosum: absent or not?

PMID- 11312205
TI  - Osteochondritis dissecans of the tibial plafond.

PMID- 11312206
TI  - September "Sonography case of the day".

PMID- 11312207
TI  - Erdheim-Chester disease of the retroperitoneum: a rare cause of ureteral
      obstruction.

PMID- 11312208
TI  - Transient gastric emphysema caused by colonic infarction.

PMID- 11312209
TI  - Isolated Candida infection of the pterygoid muscles in a patient with Gaucher's
      disease.

PMID- 11312210
TI  - Anomalous unilateral single pulmonary vein masquerading as a pulmonary
      arteriovenous malformation.

PMID- 11312211
TI  - Antibiotics for acute bronchitis.

PMID- 11312212
TI  - Injury prevention in people with disabilities.

PMID- 11312213
TI  - Do we need specialist adolescent units in hospitals?

PMID- 11312214
TI  - Haematuria in asymptomatic individuals.

PMID- 11312215
TI  - Effectiveness, efficiency, and NICE.

PMID- 11312216
TI  - Obesity and inactivity fuel global cancer epidemic.

PMID- 11312218
TI  - German heart surgeon denies corruption.

PMID- 11312221
TI  - Hungary curbs drug company advertising.

PMID- 11312220
TI  - Holland decriminalises voluntary euthanasia.

PMID- 11312222
TI  - Former treasury adviser weighs in against PFI.

PMID- 11312223
TI  - Canada acts on marijuana and tobacco.

PMID- 11312226
TI  - Requests for electroencephalography in a district general hospital: retrospective
      and prospective audit.
AB  - OBJECTIVES: To determine the number of inappropriate requests for
      electroencephalography (EEG) and whether guidelines on use could reduce this
      number. DESIGN: Audit with retrospective and prospective components. SETTING: EEG
      department in district general hospital and centre for neurology and
      neurosurgery. PARTICIPANTS: Retrospective: 368 at the general hospital and 143
      patients at the neurology centre. Prospective: 241 patients undergoing EEG at the
      general hospital. INTERVENTIONS: Guidelines for EEG issued to users of service at
      the general hospital. OUTCOMES: Retrospective: differences in requesting
      practice, result in different clinical scenarios, relative roles of procedure,
      clinical acumen in establishing diagnosis, usefulness of procedure. Prospective:
      change of requesting practice, impact on use. RESULTS: There were considerable
      differences in requesting practice. Non-specialists seem to use EEG as a
      diagnostic tool, especially in patients with "funny turns," when it is much more
      likely to yield potentially misleading than clinically useful information. The
      overall proportion of procedures considered to influence management, to be
      justifiable, and to be inappropriate were 16% (59), 28.3% (104), and 55.7% (205),
      respectively. In the prospective study the total number of requests was
      significantly reduced (chi(2)=33.85, df=5, P<0.0001), mainly because of fewer
      requests in patients with non-specific "funny turns" (chi(2)=21.90, df=6,
      P=0.0013). There was a concomitant change in the usefulness of EEG (chi(2
      )=26.99, df=2, P<0.0001). CONCLUSIONS: This original audit informed clinical
      practice and had potential benefits for patients, clinicians, and provision of
      service. Systematic replication of this project, possibly on a regional basis,
      could result in financial savings, which would allow development of accessible
      local neurophysiology services.

PMID- 11312225
TI  - Early growth and coronary heart disease in later life: longitudinal study.
AB  - OBJECTIVE: To determine how growth during infancy and childhood modifies the
      increased risk of coronary heart disease associated with small body size at
      birth. DESIGN: Longitudinal study. SETTING: Helsinki, Finland. SUBJECTS: 4630 men
      who were born in the Helsinki University Hospital during 1934-44 and who attended
      child welfare clinics in the city. Each man had on average 18.0 (SD 9.5)
      measurements of height and weight between birth and age 12 years. MAIN OUTCOME
      MEASURES: Hospital admission or death from coronary heart disease. RESULTS: Low
      birth weight and low ponderal index (birth weight/length(3)) were associated with
      increased risk of coronary heart disease. Low height, weight, and body mass index
      (weight/height(2)) at age 1 year also increased the risk. Hazard ratios fell
      progressively from 1.83 (95% confidence interval 1.28 to 2.60) in men whose body
      mass index at age 1 year was below 16 kg/m(2) to 1.00 in those whose body mass
      index was >19 (P for trend=0.0004). After age 1 year, rapid gain in weight and
      body mass index increased the risk of coronary heart disease. This effect was
      confined, however, to men with a ponderal index <26 at birth. In these men the
      hazard ratio associated with a one unit increase in standard deviation score for
      body mass index between ages 1 and 12 years was 1.27 (1.10 to 1.47; P=0.001).
      CONCLUSION: Irrespective of size at birth, low weight gain during infancy is
      associated with increased risk of coronary heart disease. After age 1 year, rapid
      weight gain is associated with further increase in risk, but only among boys who
      were thin at birth. In these boys the adverse effects of rapid weight gain on
      later coronary heart disease are already apparent at age 3 years. Improvements in
      fetal, infant, and child growth could lead to substantial reductions in the
      incidence of coronary heart disease.

PMID- 11312227
TI  - National survey of use of hospital beds by adolescents aged 12 to 19 in the
      United Kingdom.

PMID- 11312228
TI  - Anaemia in Chinese, South Asian, and European populations in Newcastle upon Tyne:
      cross sectional study.

PMID- 11312229
TI  - How private finance is moving primary care into corporate ownership.

PMID- 11312230
TI  - Will primary care trusts lead to US-style health care?

PMID- 11312232
TI  - Extracts from "clinical evidence": hip fracture.

PMID- 11312233
TI  - Lesson of the week: tonic seizures are a particular risk factor for drowning in
      people with epilepsy.

PMID- 11312234
TI  - Evidence based management of hypertension. Cardiovascular risk factors and their
      effects on the decision to treat hypertension: evidence based review.

PMID- 11312235
TI  - ABC of hypertension. Blood pressure measurement. Part I-sphygmomanometry: factors
      common to all techniques.

PMID- 11312236
TI  - Should we screen for type 2 diabetes? Evaluation against National Screening
      Committee criteria.

PMID- 11312237
TI  - Interpreting the results of secondary end points and subgroup analyses in
      clinical trials: should we lock the crazy aunt in the attic?

PMID- 11312238
TI  - Not reading and signing letters you have dictated is dangerous.

PMID- 11312239
TI  - Hospital league tables. There are lies, damn lies, and hospital statistics.

PMID- 11312240
TI  - "Old age" should be not be acceptable on death certificates.

PMID- 11312241
TI  - Headache after diagnostic lumbar puncture. Using 20 gauge needle is blunderbuss
      technique.

PMID- 11312242
TI  - Hospital league tables. Analysis is flawed.

PMID- 11312243
TI  - Headache after diagnostic lumbar puncture. Smaller is better where needles are
      concerned.

PMID- 11312244
TI  - Opportunity may be more important than profession in serial homicide.

PMID- 11312245
TI  - Headache after diagnostic lumbar puncture. Authors should have used smaller gauge
      needles.

PMID- 11312246
TI  - Headache after diagnostic lumbar puncture. Doctors given intrathecal methotrexate
      had headache when 20 gauge standard needle was used.

PMID- 11312247
TI  - Strengthening governance for global health research. Improved undergraduate and
      postgraduate training may raise awareness.

PMID- 11312248
TI  - Antigen-specific T(h)1 cells as direct effectors of Propionibacterium acnes
      primed lipopolysaccharide-induced hepatic injury.
AB  - T(h)1 cells are cytotoxic effector cells that utilize Fas ligand (FasL) and tumor
      necrosis factor. The physiological roles of cytotoxic T(h)1 cells are considered
      to be immunoregulation by eliminating autoreactive lymphocytes or hyper-activated
      foreign antigen-specific lymphocytes. Their pathological roles, however, remain
      to be clarified. To investigate whether T(h)1 cells can destroy organs, we
      generated a Propionibacterium acnes-specific T(h)1 clone from C57BL/6 mice and
      tested whether the clone could serve as an effector in a P. acnes-primed
      lipopolysaccharide (LPS)-induced hepatic injury system, one of the septic shock
      models. B6SMN:C3H-FasL(gld) (B6-gld) mice, which were deficient in functional
      FasL, were resistant to P. acnes/LPS-induced hepatic shock. The T(h)1 clone
      rendered B6-gld mice sensitive to the hepatic shock after the i.v. transfer. The
      hepatic injury in the clone-transferred B6-gld mice, which was evaluated by both
      biochemical and histological examination, was inhibited by an anti-FasL mAb that
      we developed. These results suggested that bacterial antigen-specific T(h)1 cells
      like this clone can participate in organ destruction in vivo as one of the
      cytotoxic effectors and play a critical role in endotoxin-induced hepatic injury.

PMID- 11312249
TI  - H-2 allele specificity of the NK cell C-type lectin-like MHC class I receptor
      Ly49A visualized by soluble Ly49A tetramer.
AB  - Ly49A is a C-type lectin-like receptor on NK cells that recognizes MHC class I
      ligands, H-2D(d) and D(k). The engagement of Ly49A with the ligands inhibits
      activation of NK cells and protects target cells from lysis by NK cells. Here we
      express the extracellular region of Ly49A with an N-terminal biotinylation tag in
      Escherichia coli to obtain soluble Ly49A (sLy49A) after refolding. sLy49A is
      indistinguishable from native Ly49A expressed on NK cells serologically and in
      the ability to specifically bind H-2D(d) after tetramerization with R
      phycoerythrin-coupled streptavidin. The fluorescently labeled tetramer of sLy49A
      is applied to explore MHC class I haplotype specificity of Ly49A. We demonstrate
      the hierarchical reactivity of Ly49A with H-2 of various alleles in the order of
      d > k, r > p > v > q > s > z. Reactivity of sLy49A tetramer to spleen lymphocytes
      from B10.QBR mice (H-2K(b), I(b), D(q), Qa-1/Tla(b)) but not from C57BL/10 mice
      (H-2(b)) identifies H-2D(q) and L(q) as candidates for a Ly49A ligand. Binding of
      sLy49A tetramer to H-2D(q)- or L(q)-transfected cell lines demonstrates that the
      two highly related MHC class I molecules, H-2D(q) and L(q), are ligands for
      Ly49A. sLy49A tetramer staining also demonstrates preferential expression of
      Ly49A ligand on a subset of B cells in P/J mice. These results provide the basis
      to examine the molecular mechanism by which Ly49A discriminates polymorphic MHC
      class I molecules.

PMID- 11312250
TI  - Epitope spreading upon P815 tumor rejection triggered by vaccination with the
      single class I MHC-restricted peptide P1A.
AB  - Epitope spreading has been best characterized as an exacerbating factor in CD4(+)
      T cell-dependent autoimmune disease models and is believed to occur via
      presentation of antigens liberated by tissue destruction initiated by CD4(+) T
      cells specific for a primary epitope. The growing evidence that exogenous
      antigens can also be processed and presented by class I MHC molecules has
      suggested that epitope spreading could occur for CD8(+) cytotoxic T lymphocyte
      (CTL) responses as well. In the context of anti-tumor immunity, expansion of a
      CTL response to include secondary epitopes could improve the efficacy of
      therapeutic vaccines. To determine directly whether epitope spreading can occur
      during an anti-tumor immune response, two defined class I MHC-binding peptides in
      the P815 tumor model were utilized. We observed that immunization against the
      single tumor peptide, P1A, followed by rejection of a P1A(+) tumor, subsequently
      yielded CTL activity and tumor protection against a P1A(-) tumor variant. P1A
      immunized mice that subsequently rejected tumor challenge developed CTL against a
      second defined epitope, P1E. These results indicate that, as for class II
      restricted peptides in autoimmune disease, epitope spreading can occur for class
      I-restricted peptides during tumor rejection. A broadened CTL response may help
      eliminate outgrowth of antigen-negative tumor variants.

PMID- 11312251
TI  - Physical interaction of human papillomavirus virus-like particles with immune
      cells.
AB  - Human papillomavirus virus-like particles (HPV VLP) and chimeric VLP are
      immunogens that are able to elicit potent anti-viral/tumor B and T cell
      responses. To investigate the immunogenicity of VLP, we determined which cells of
      the immune system are able to bind HPV-16 VLP. VLP were found to bind very well
      to human and mouse immune cells that expressed markers of antigen-presenting
      cells (APC) such as MHC class II, CD80 and CD86, including dendritic cells,
      macrophages and B cells. mAb blocking studies identified Fc gamma RIII (CD16) as
      one of the molecules to which the VLP can bind both on immune cells and foreskin
      epithelium. However, transfection of a CD16(-) cell line with CD16 did not confer
      binding of VLP. Splenocytes from Fc gamma RIII knockout mice showed a 33%
      decrease in VLP binding overall and specifically to subsets of APC. These
      combined data support a role for CD16 as an accessory molecule in an HPV VLP
      receptor complex, possibly contributing to the immunogenicity of HPV VLP.

PMID- 11312252
TI  - Canonical germinal center B cells may not dominate the memory response to
      antigenic challenge.
AB  - Spleen and bone marrow (BM) are the major sites of antibody production and
      anamnestic response in systemically immunized mice. We examined the VDJ segment
      repertoire of antibody plaque-forming cells (APFC) in those two sites in the
      course of antibody responses to the hapten nitrophenyl (NP). Individual IgG APFC
      expressed any one of 10 V(H) segments of the V186.2/V3 (J558) gene family: 186.2,
      102, 23, C1H4, 165.l, CH10, 3, 593.3, 24.8 and 671.5. The majority of cells in
      both spleen and BM expressed the V186.2 gene joined to a D segment with Tyr95.
      During a 2-month period after a single immunization, the V186.2(+) APFC in BM
      accumulated 3 times as many somatic mutations than splenic APFC (average 8.5
      versus 3 mutations/V(H)); this process was T(h) dependent as shown by in vivo
      depletion of CD4(+) lymphocytes. However, the V186.2(+) APFC in both spleen and
      BM shared a recurrent W33L replacement, indicating their common origin from
      germinal centers. The APFC expressing the other (analogue) V(H) segments were
      evenly represented in the spleen and BM, but they accumulated few, if any,
      mutations. The anamnestic V186.2(+) APFC were highly mutated both in the spleen
      and BM; they represented a new and unexpected clonotype. The V/D segments were
      joined by Gly95 instead of Tyr95, the W33L was absent and a new shared K58R
      replacement appeared. The APFC expressing the 'analogue' V(H) genes comprised
      approximately 20% of the anamnestic response and did not accumulate more
      mutations, but their affinities were in the range of the memory V186.2(+) cells.
      These data suggest that the late primary and secondary responses to a hapten may
      be born by different B cell lineages, and that some clonotypes may reach the
      memory pool without an extensive mutation and expansion.

PMID- 11312253
TI  - A site in the complement receptor 2 (CR2/CD21) silencer is necessary for lineage
      specific transcriptional regulation.
AB  - Expression of human complement receptor type 2 (CR2/CD21) is primarily restricted
      to mature B cells and follicular dendritic cells. We previously described an
      intronic transcriptional silencer that controls the appropriate B cell-specific
      and developmentally restricted expression of human CR2/CD21 in both stably
      transfected cell lines and transgenic mice. Here we report the identification of
      a nucleotide sequence within the 2.5 kb CR2 silencer (CRS) that is crucial to its
      silencer function. This site comprises a binding site for the transcriptional
      repressor CBF1 (RBP-J or RBP-Jkappa) as well as Sp1 and other as yet
      uncharacterized proteins. A 2-bp mutation which eliminates the binding of CBF1
      and other protein(s) in vitro results in loss of silencer activity in vivo. These
      results demonstrate the importance of this site in regulating CR2 expression and
      suggest that CBF1, a component of the developmentally important Notch signaling
      pathway, may play a role in the control of human CR2 gene expression.

PMID- 11312254
TI  - The 3' Igkappa enhancer contains RNA polymerase II promoters: implications for
      endogenous and transgenic kappa gene expression.
AB  - We have created a kappa transgene in which a polymerase (pol) III promoter
      replaces the pol II promoter. Two independent transgenic lines show somatic
      hypermutation of the transgene in B cells from hyperimmunized mice. Both lines
      transcribe transgenes from the pol III promoter in the liver. However, in spleen
      and spleen B cell-derived hybridomas, they also transcribe mRNA from pol II
      promoters located within the 3' kappa enhancer of the preceding transgene copy in
      a tandem transgene array. The findings demonstrate that in an array of multiple
      transgenes the expression (and somatic hypermutation) of an individual transgene
      copy must be considered in the context of the other copies. We also show that
      sequences around the 3' kappa enhancer in endogenous genes are transcribed. The
      possible role of these promoters in endogenous kappa gene expression is
      discussed. An unrelated finding in this study was a novel RNA splice in one
      hybridoma.

PMID- 11312255
TI  - Effective antigen presentation by dendritic cells is NF-kappaB dependent:
      coordinate regulation of MHC, co-stimulatory molecules and cytokines.
AB  - Antigen presentation is a key rate-limiting step in the immune response.
      Dendritic cells (DC) are the most potent antigen-presenting cells for naive T
      cells, due to their high expression of MHC and co-stimulatory molecules, but
      little is known about the biochemical pathways that regulate this function. We
      here demonstrate that monocyte-derived mature DC can be infected with adenovirus
      at high efficiency (>95%) and that this procedure can be used to dissect out
      which pathways are essential for inducing DC antigen presentation to naive T
      cells. Using adenoviral transfer of the endogenous inhibitor of NF-kappaB,
      IkappaBalpha, we show that DC antigen presentation is NF-kappaB dependent. The
      mechanism for this is that NF-kappaB is essential for three aspects of antigen
      presenting function: blocking NF-kappaB coordinately down-regulates HLA class II,
      co-stimulatory molecules like CD80, CD86 and CD40, and immuno-stimulatory
      cytokines like IL-12 and tumor necrosis factor-alpha. In contrast adhesion
      molecules are up-regulated after infection with the adenovirus transferring
      IkappaBalpha, indicating that NF-kappaB also regulates the duration of T cell-DC
      interaction. These results establish NF-kappaB as an effective target for
      blocking DC antigen presentation and inhibiting T cell-dependent immune
      responses, and this finding has potential implications for the development of
      therapeutic agents for use in allergy, autoimmunity and transplantation.

PMID- 11312256
TI  - Suppression of T(h)1 cell activation and prevention of autoimmune diabetes in NOD
      mice by local expression of viral IL-10.
AB  - Insulin-dependent diabetes mellitus in the NOD mouse model is caused by the T
      cell-mediated autoimmune destruction of pancreatic beta cells. Viral IL-10 (vIL
      10), encoded in the Epstein-Barr virus genome, shares many of the anti
      inflammatory properties of cellular IL-10, but lacks its immunostimulatory
      properties. In the present study, we generated transgenic (Tg) NOD mice in which
      vIL-10 was produced exclusively in pancreatic islets and investigated the effect
      of vIL-10 on the development of diabetes. The accumulation of lymphocytes around
      islets was more prominent, but the invasive insulitis decreased in the vIL-10 Tg
      mice. The incidence of diabetes was markedly reduced in the vIL-10 Tg mice, in
      clear contrast to the accelerated diabetes seen in the murine IL-10 Tg NOD mice.
      IL-12p40 and IFN-gamma mRNA levels were decreased in pancreata of the vIL-10 Tg
      mice, although CD4 mRNA level was markedly increased. These results suggest that
      locally produced vIL-10 induced leukocyte migration, but inhibited the activation
      of T(h)1, probably through suppressing the production of IL-12. They indicate
      that vIL-10 may well be superior to cellular IL-10 in the treatment of autoimmune
      diabetes. The vIL-10 Tg NOD mice should provide a useful tool for understanding
      the differential action of vIL-10 versus cellular IL-10.

PMID- 11312257
TI  - Skin antigens in the steady state are trafficked to regional lymph nodes by
      transforming growth factor-beta1-dependent cells.
AB  - Antigen capturing in the skin and antigen trafficking into regional lymph nodes
      (LN) initiate immune responses. In this study, employing melanin granule (MG) as
      an easily traceable antigen in two mouse strains that carried steel factor or
      hepatocyte growth factor transgenes and had melanocytosis in the epidermis or in
      the dermis respectively, we investigated the mechanism of antigen trafficking
      from the skin. MG captured in the epidermis or dermis accumulated in the regional
      LN, but not other tissues. Only in alymphoplastic mice did MG-laden cells pass
      through the lymphatics and reached many tissues. Since inflammatory regions were
      not observed in the skin of either type of transgenic mouse, our developmental
      system enables us to investigate constitutive capturing and trafficking of
      insoluble antigens in the steady state. Both dendritic cells and macrophages were
      laden with MG in the regional LN. To determine which cells traffic antigens to
      the LN, we prepared double mutants that carried the transgenes and lacked
      transforming growth factor (TGF)-beta1, since mice lacking TGF-beta1 are reported
      to be deficient of Langerhans cells. Few MG were observed in the regional LN of
      these double-mutant mice. We also showed that signaling via macrophage colony
      stimulating factor receptor or Flt3/Flk2 is not essential for development of the
      cells for this antigen trafficking. These results indicate that antigens in the
      epidermis and dermis in the steady state are trafficked into regional LN only by
      TGF-beta1-dependent cells, which may be a dendritic cell lineage.

PMID- 11312258
TI  - Regulation of CD21 expression by DNA methylation and histone deacetylation.
AB  - The complement receptor II (CD21) serves as a receptor for the complement
      component C3d of immune complexes on B lymphocytes. Expression of the CD21 gene
      is tightly regulated during B lymphocyte differentiation. Only mature B
      lymphocytes, but not pro-, pre- or plasma B lymphocytes, express CD21. There is
      evidence that cell type-specific expression is mediated by a silencer element
      located in the first intron. The CD21 promoter region contains a CpG island
      adjacent to the ATG start codon. We have analyzed the methylation status of this
      CpG island in B lymphoid cell lines representing the various differentiation
      stages of B lymphocyte development and primary lymphocytes. We found that the pro
      , pre- and intermediate B lymphocytes contain a methylated CpG island and do not
      express CD21, whereas CD21-expressing mature B lymphocytes, plasma B lymphocytes
      and non-lymphoid cells carry a demethylated CD21 CpG island. To analyze whether
      the lack of CD21 expression in early B lymphocytes is due to inhibition by CpG
      methylation we have used 5-aza-2'-deoxycytidine to inhibit DNA methyltransferase
      activity. Treatment of pro-B lymphocytes with the drug resulted in expression of
      CD21. We have also applied Trichostatin A (TSA), an inhibitor of histone
      deacetylation, to determine whether the state of histone deacetylation affects
      the expression of CD21. We found that TSA induces expression of CD21 in early B
      lymphocytes. Thus CD21 expression is controlled by both methylation of the CD21
      CpG island and chromatin modification through histone deacetylation in early B
      lymphocyte development.

PMID- 11312259
TI  - The omega-loop region of the human prothrombin gamma-carboxyglutamic acid domain
      penetrates anionic phospholipid membranes.
AB  - The hydrophobic omega-loop within the prothrombin gamma-carboxyglutamic acid-rich
      (Gla) domain is important in membrane binding. The role of this region in
      membrane binding was investigated using a synthetic peptide, PT-(1-46)F4W, which
      includes the N-terminal 46 residues of human prothrombin with Phe-4 replaced by
      Trp providing a fluorescent probe. PT-(1-46)F4W and PT-(1-46) bind calcium ions
      and phospholipid membranes, and inhibit the prothrombinase complex. PT-(1-46)F4W,
      but not PT-(1-46), exhibits a blue shift (5 nm) and red-edge excitation shift (28
      nm) in the presence of phosphatidylserine (PS)-containing vesicles, suggesting
      Trp-4 is located within the motionally restricted membrane interfacial region. PS
      containing vesicles protect PT-(1-46)F4W, but not PT-(1-46), fluorescence from
      potassium iodide-induced quenching. Stern-Volmer analysis of the quenching of PT
      (1-46)F4W in the presence and absence of 80% phosphatidylcholine/20% PS vesicles
      suggested that Trp-4 is positioned within the membrane and protected from aqueous
      quenching agents whereas Trp-41 remains solvent-accessible in the presence of PS
      containing vesicles. Fluorescence quenching of membrane-bound PT-(1-46)F4W is
      optimal with 7- and 10-doxyl-labeled lipids, indicating that Trp-4 is inserted 5
      to 7 A into the bilayer. This report demonstrates that the omega-loop region of
      prothrombin specifically interacts with PS-containing membranes within the
      interfacial membrane region.

PMID- 11312260
TI  - CCAAT/enhancer-binding protein beta mediates interferon-gamma-induced p48 (ISGF3
      gamma ) gene transcription in human monocytic cells.
AB  - Previous studies have identified a novel interferon-stimulated response element
      like element, termed gamma-interferon-activating transcription element, within
      the interferon-stimulating gene factor-3gamma (p48) promoter region that is bound
      by novel transcription factors in response to stimulation with interferons (IFNs)
      (Weihua, X., Kolla, V., and Kalvakolanu, D. V. (1997) Proc. Natl. Acad. Sci. U.
      S. A. 94, 103-108). In the present study, we have identified CCAAT/enhancer
      binding protein beta (C/EBP-beta) as one of the gamma-interferon-activating
      transcription element cognate transcription factors by screening a human
      monophage-derived cDNA library in a yeast one-hybrid system. Electrophoretic
      mobility shift assay studies suggest that C/EBP-beta dynamically regulates p48
      gene expression upon IFN-gamma stimulation by undergoing changes in its
      heterodimerization partners. Transient transfection studies demonstrate that
      overexpression of C/EBP-beta strongly enhanced IFN-gamma-induced transcription
      from the p48 promoter. However, deletion mutants of C/EBP-beta that lack the N
      terminal transactivation domain were unable to stimulate the p48 promoter.
      Western blotting revealed that C/EBP-beta is induced by IFN-gamma stimulation in
      THP-1-derived macrophages. Collectively, these results suggest that C/EBP-beta
      plays an important role in the human IFN-gamma signaling pathway by
      transcriptional regulation of p48 gene expression, an essential component in the
      IFN signaling pathway.

PMID- 11312261
TI  - Positive and negative regulation of myogenic differentiation of C2C12 cells by
      isoforms of the multiple homeodomain zinc finger transcription factor ATBF1.
AB  - The ATBF1 gene encodes two protein isoforms, the 404-kDa ATBF1-A, possessing four
      homeodomains and 23 zinc fingers, and the 306-kDa ATBF1-B, lacking a 920-amino
      acid N-terminal region of ATBF1-A which contains 5 zinc fingers. In vitro, ATBF1
      A was expressed in proliferating C2C12 myoblasts, but its expression levels
      decreased upon induction of myogenic differentiation in low serum medium. Forced
      expression of ATBF1-A in C2C12 cells resulted in repression of MyoD and myogenin
      expression and elevation of Id3 and cyclin D1 expression, leading to inhibition
      of myogenic differentiation in low serum. In contrast, transfection of C2C12
      cells with the ATBF1-B isoform led to an acceleration of myogenic
      differentiation, as indicated by an earlier onset of myosin heavy chain
      expression and formation of a higher percentage of multinucleated myotubes. The
      fourth homeodomain of ATBF1-A bound to an AT-rich element adjacent to the E1 E
      box of the muscle regulatory factor 4 promoter mediating transcriptional
      repression. The ATBF1-A-specific N-terminal region possesses general
      transcription repressor activity. These results suggest that ATBF1-A plays a role
      in the maintenance of the undifferentiated myoblast state, and its down
      regulation is a prerequisite to initiate terminal differentiation of C2C12 cells.

PMID- 11312262
TI  - A central role for the T1 domain in voltage-gated potassium channel formation and
      function.
AB  - To interpret the recent atomic structures of the Kv (voltage-dependent potassium)
      channel T1 domain in a functional context, we must understand both how the T1
      domain is integrated into the full-length functional channel protein and what
      functional roles the T1 domain governs. The T1 domain clearly plays a role in
      restricting Kv channel subunit heteromultimerization. However, the importance of
      T1 tetramerization for the assembly and retention of quarternary structure within
      full-length channels has remained controversial. Here we describe a set of
      mutations that disrupt both T1 assembly and the formation of functional channels
      and show that these mutations produce elevated levels of the subunit monomer that
      becomes subject to degradation within the cell. In addition, our experiments
      reveal that the T1 domain lends stability to the full-length channel structure,
      because channels lacking the T1 containing N terminus are more easily denatured
      to monomers. The integration of the T1 domain ultrastructure into the full-length
      channel was probed by proteolytic mapping with immobilized trypsin. Trypsin
      cleavage yields an N-terminal fragment that is further digested to a tetrameric
      domain, which remains reactive with antisera to T1, and that is similar in size
      to the T1 domain used for crystallographic studies. The trypsin-sensitive
      linkages retaining the T1 domain are cleaved somewhat slowly over hours.
      Therefore, they seem to be intermediate in trypsin resistance between the rapidly
      cleaved extracellular linker between the first and second transmembrane domains,
      and the highly resistant T1 core, and are likely to be partially structured or
      contain dynamic structure. Our experiments suggest that tetrameric atomic models
      obtained for the T1 domain do reflect a structure that the T1 domain sequence
      forms early in channel assembly to drive subunit protein tetramerization and that
      this structure is retained as an integrated stabilizing structural element within
      the full-length functional channel.

PMID- 11312263
TI  - The giant protein AHNAK is a specific target for the calcium- and zinc-binding
      S100B protein: potential implications for Ca2+ homeostasis regulation by S100B.
AB  - Transformation of rat embryo fibroblast clone 6 cells by ras and temperature
      sensitive p53val(135) is reverted by ectopic expression of the calcium- and zinc
      binding protein S100B. In an attempt to define the molecular basis of the S100B
      action, we have identified the giant phosphoprotein AHNAK as the major and most
      specific Ca(2+)-dependent S100B target protein in rat embryo fibroblast cells. We
      next characterized AHNAK as a major Ca(2+)-dependent S100B target protein in the
      rat glial C6 and human U-87MG astrocytoma cell lines. AHNAK binds to S100B
      Sepharose beads and is also recovered in anti-S100B immunoprecipitates in a
      strict Ca(2+)- and Zn(2+)-dependent manner. Using truncated AHNAK fragments, we
      demonstrated that the domains of AHNAK responsible for interaction with S100B
      correspond to repeated motifs that characterize the AHNAK molecule. These motifs
      show no binding to calmodulin or to S100A6 and S100A11. We also provide evidence
      that the binding of 2 Zn(2+) equivalents/mol S100B enhances Ca(2+)-dependent
      S100B-AHNAK interaction and that the effect of Zn(2+) relies on Zn(2+)-dependent
      regulation of S100B affinity for Ca(2+). Taking into consideration that AHNAK is
      a protein implicated in calcium flux regulation, we propose that the S100B-AHNAK
      interaction may participate in the S100B-mediated regulation of cellular Ca(2+)
      homeostasis.

PMID- 11312264
TI  - An extensive interaction interface between thrombin and factor V is required for
      factor V activation.
AB  - The interaction interface between human thrombin and human factor V (FV),
      necessary for complex formation and cleavage to generate factor Va, was
      investigated using a site-directed mutagenesis strategy. Fifty-three recombinant
      thrombins, with a total of 78 solvent-exposed basic and polar residues
      substituted with alanine, were used in a two-stage clotting assay with human FV.
      Seventeen mutants with less than 50% of wild-type (WT) thrombin FV activation
      were identified and mapped to anion-binding exosite I (ABE-I), anion-binding
      exosite II (ABE-II), the Leu(45)-Asn(57) insertion loop, and the Na(+) binding
      loop of thrombin. Three ABE-I mutants (R68A, R70A, and Y71A) and the ABE-II
      mutant R98A had less than 30% of WT activity. The thrombin Na(+) binding loop
      mutants, E229A and R233A, and the Leu(45)-Asn(57) insertion loop mutant, W50A,
      had a major effect on FV activation with 5, 15, and 29% of WT activity,
      respectively. The K52A mutant, which maps to the S' specificity pocket, had 29%
      of WT activity. SDS-polyacrylamide gel electrophoresis analysis of cleavage
      reactions using the thrombin ABE mutants R68A, Y71A, and R98A, the Na(+) binding
      loop mutant E229A, and the Leu(45)-Asn(57) insertion loop mutant W50A showed a
      requirement for both ABEs and the Na(+)-bound form of thrombin for efficient
      cleavage at the FV residue Arg(709). Several basic residues in both ABEs have
      moderate decreases in FV activation (40-60% of WT activity), indicating a role
      for the positive electrostatic fields generated by both ABEs in enhancing complex
      formation with complementary negative electrostatic fields generated by FV. The
      data show that thrombin activation of FV requires an extensive interaction
      interface with thrombin. Both ABE-I and ABE-II and the S' subsite are required
      for optimal cleavage, and the Na(+)-bound form of thrombin is important for its
      procoagulant activity.

PMID- 11312265
TI  - Comparative in vitro studies on native and recombinant human cationic trypsins.
      Cathepsin B is a possible pathological activator of trypsinogen in pancreatitis.
AB  - Hereditary pancreatitis, an autosomal dominant disease is believed to be caused
      by mutation in the human trypsinogen gene. The role of mutations has been
      investigated by in vitro studies using recombinant rat and human trypsinogen
      (TG). In this study we compare the enzymatic properties and inhibition by human
      pancreatic secretory trypsin inhibitor (hPSTI) of the native, postsynthetically
      modified and recombinant cationic trypsin, and found these values practically
      identical. We also determined the autolytic stability of recombinant wild type
      (Hu1Asn21) and pancreatitis-associated (Hu1Ile21) trypsin. Both forms were
      equally stable. Similarly, we found no difference in the rate of activation of
      the two zymogens by human cationic and anionic trypsin. Mesotrypsin did not
      activate either form. The rate of autocatalytic activation of Hu1Asn21 TG and
      Hu1Ile21 TG was also identical at pH 8 both in the presence and absence of Ca2+.
      At pH 5 Hu1Ile21 TG autoactivated about twice as fast as Hu1Asn21 TG. The
      presence of physiological amount of hPSTI completely prevented autoactivation of
      both zymogens at pH 8 and at pH 5 as well. Cathepsin B readily activated both
      zymogens although Hu1Ile21 TG was activated about 2.5-3 times as fast as Hu1Asn21
      TG. The presence of hPSTI did not prevent the activation of zymogens by cathepsin
      B. Our results underlie the central role of cathepsin B in the development of
      different forms of pancreatitis.

PMID- 11312266
TI  - The p75 neurotrophin receptor activates Akt (protein kinase B) through a
      phosphatidylinositol 3-kinase-dependent pathway.
AB  - The Akt kinase plays a crucial role in supporting Trk-dependent cell survival,
      whereas the p75 neurotrophin receptor (p75NTR) facilitates cellular apoptosis.
      The precise mechanism that p75NTR uses to promote cell death is not certain, but
      one possibility is that p75NTR-dependent ceramide accumulation inhibits
      phosphatidylinositol 3-kinase-mediated Akt activation. To test this hypothesis,
      we developed a system for examining p75NTR-dependent apoptosis and determined the
      effect of p75NTR on Akt activation. Surprisingly, p75NTR increased, rather than
      decreased, Akt phosphorylation in a variety of cell types, including human
      Niemann-Pick fibroblasts, which lack acidic sphingomyelinase activity. The p75NTR
      expression level required to elicit Akt phosphorylation was much lower than that
      required to activate the JNK pathway or to mediate apoptosis. We show that p75NTR
      dependent Akt phosphorylation was independent of TrkA signaling, required active
      phosphatidylinositol 3-kinase, and was associated with increased tyrosine
      phosphorylation of p85 and Shc and with reduced cytosolic tyrosine phosphatase
      activity. Finally, we show that p75NTR expression increased survival in cells
      exposed to staurosporine or subjected to serum withdrawal. These findings
      indicate that p75NTR facilitates cell survival through novel signaling cascades
      that result in Akt activation.

PMID- 11312267
TI  - Characterization of the magnitude and kinetics of xanthine oxidase-catalyzed
      nitrite reduction. Evaluation of its role in nitric oxide generation in anoxic
      tissues.
AB  - Xanthine oxidase (XO)-catalyzed nitrite reduction with nitric oxide (NO)
      production has been reported to occur under anaerobic conditions, but questions
      remain regarding the magnitude, kinetics, and biological importance of this
      process. To characterize this mechanism and its quantitative importance in
      biological systems, electron paramagnetic resonance spectroscopy,
      chemiluminescence NO analyzer, and NO electrode studies were performed. The XO
      reducing substrates xanthine, NADH, and 2,3-dihydroxybenz-aldehyde triggered
      nitrite reduction to NO, and the molybdenum-binding XO inhibitor oxypurinol
      inhibited this NO formation, indicating that nitrite reduction occurs at the
      molybdenum site. However, at higher xanthine concentrations, partial inhibition
      was seen, suggesting the formation of a substrate-bound reduced enzyme complex
      with xanthine blocking the molybdenum site. Studies of the pH dependence of NO
      formation indicated that XO-mediated nitrite reduction occurred via an acid
      catalyzed mechanism. Nitrite and reducing substrate concentrations were important
      regulators of XO-catalyzed NO generation. The substrate dependence of anaerobic
      XO-catalyzed nitrite reduction followed Michaelis-Menten kinetics, enabling
      prediction of the magnitude of NO formation and delineation of the quantitative
      importance of this process in biological systems. It was determined that under
      conditions occurring during no-flow ischemia, myocardial XO and nitrite levels
      are sufficient to generate NO levels comparable to those produced from nitric
      oxide synthase. Thus, XO-catalyzed nitrite reduction can be an important source
      of NO generation under ischemic conditions.

PMID- 11312268
TI  - Cellular and subcellular localization, N-terminal acylation, and calcium binding
      of Caenorhabditis elegans protein phosphatase with EF-hands.
AB  - The RdgC/PPEF family of serine/threonine protein phosphatases is distinguished by
      the presence of C-terminal EF-hands and neuron-specific expression, including
      frequent expression in primary sensory neurons. Here we report that the sole
      Caenorhabditis elegans PPEF (CePPEF) homolog is also highly expressed in primary
      sensory neurons and is not found outside the nervous system. Neurons expressing
      CePPEF include the ciliary chemosensory neurons AWB and AWC; and within these
      neurons, CePPEF is highly enriched in the sensory cilia. In transgenic C. elegans
      and in transfected 293 cells, CePPEF is membrane-associated, and the N terminus
      of CePPEF is necessary and sufficient for this membrane association.
      [(3)H]Myristate and [(3)H]palmitate labeling studies in 293 cells demonstrated
      that this association was mediated by myristoylation at Gly(2) and palmitoylation
      at Cys(3). Introducing the G2A or C3S mutation into CePPEF greatly reduced
      membrane association in 293 cells and in transgenic nematodes. A recombinant C
      terminal fragment of CePPEF containing two putative EF-hands bound between one
      and two Ca(2+) ions/protein, and mutation of residues presumed to ligand calcium
      in the two putative EF-hands led to diminished calcium binding. These results
      establish the first direct evidence for fatty acylation and calcium binding of a
      PPEF family member and demonstrate a remarkable conservation of sensory neuron
      expression among the members of this distinctive family of protein phosphatases.

PMID- 11312269
TI  - A spirochete surface protein uncouples store-operated calcium channels in
      fibroblasts: a novel cytotoxic mechanism.
AB  - The cytotoxicity of infectious agents can be mediated by disruption of calcium
      signaling in target cells. Outer membrane proteins of the spirochete Treponema
      denticola, a periodontal pathogen, inhibit agonist-induced Ca(2+) release from
      internal stores in gingival fibroblasts, but the mechanism is not defined. We
      determined here that the major surface protein (Msp) of T. denticola perturbs
      calcium signaling in human fibroblasts by uncoupling store-operated channels. Msp
      localized in complexes on the cell surface. Ratio fluorimetry showed that in
      cells loaded with fura-2 or fura-C18, Msp induced cytoplasmic and near-plasma
      membrane Ca(2+) transients, respectively. Increased conductance was confirmed by
      fluorescence quenching of fura-2-loaded cells with Mn(2+) after Msp treatment.
      Calcium entry was blocked with anti-Msp antibodies and inhibited by chelating
      external Ca(2+) with EGTA. Msp pretreatment reduced the amplitude of [Ca(2+)](i)
      transients upon challenge with ATP or thapsigargin. In experiments using cells
      loaded with mag-fura-2 to report endoplasmic reticulum Ca(2+), Msp reduced Ca(2+)
      efflux from endoplasmic reticulum stores when ATP was used as an agonist. Msp
      alone did not induce Ca(2+) release from these stores. Msp inhibited store
      operated influx of extracellular calcium following intracellular Ca(2+) depletion
      by thapsigargin and also promoted the assembly of subcortical actin filaments.
      This actin assembly was blocked by chelating intracellular Ca(2+) with 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester. The reduced
      amplitude of agonist-induced transients and inhibition of store-operated Ca(2+)
      entry due to Msp were reversed by latrunculin B, an inhibitor of actin filament
      assembly. Thus, Msp retards Ca(2+) release from endoplasmic reticulum stores, and
      it inhibits subsequent Ca(2+) influx by uncoupling store-operated channels. Actin
      filament rearrangement coincident with conformational uncoupling of store
      operated calcium fluxes is a novel mechanism by which surface proteins and toxins
      of pathogenic microorganisms may damage host cells.

PMID- 11312270
TI  - Inducible nitric-oxide synthase is regulated by the proteasome degradation
      pathway.
AB  - Inducible nitric-oxide synthase (iNOS) is responsible for nitric oxide (NO)
      synthesis from l-arginine in response to inflammatory mediators. To determine the
      degradation pathway of iNOS, human epithelial kidney HEK293 cells with stable
      expression of human iNOS were incubated in the presence of various degradation
      pathway inhibitors. Treatment with the proteasomal inhibitors lactacystin, MG132,
      and N-acetyl-l-leucinyl-l-leucinyl-l-norleucinal resulted in the accumulation of
      iNOS, indicating that these inhibitors blocked its degradation. Moreover,
      proteasomal inhibition blocked iNOS degradation in a dose- and time-dependent
      manner as well as when NO synthesis was inhibited by N(omega)-nitro-l-arginine
      methyl ester. Furthermore, proteasomal inhibition blocked the degradation of an
      iNOS splice variant that lacked the capacity to dimerize and of an iNOS mutant
      that lacks l-arginine binding ability, suggesting that iNOS is targeted by
      proteasomes, notwithstanding its capacity to produce NO, dimerize, or bind the
      substrate. In contrast to proteasomal inhibitors, the calpain inhibitor
      calpastatin and the lysosomal inhibitors trans-epoxysuccinyl-l-leucylamido-4
      guanidino butane, leupeptin, pepstatin-A, chloroquine, and NH(4)Cl did not lead
      to significant accumulation of iNOS. Interestingly, when cytokines were used to
      induce iNOS in RT4 human epithelial cells, the effect of proteasomal inhibition
      was dichotomous. Lactacystin added prior to cytokine stimulation prevented iNOS
      induction by blocking the degradation of the NF-kappaB inhibitor IkappaB-alpha,
      thus preventing activation of NF-kappaB. In contrast, lactacystin added 48 h
      after iNOS induction led to the accumulation of iNOS. Similarly, in murine
      macrophage cell line RAW 264.7, lactacystin blocked iNOS degradation when added
      48 h after iNOS induction by lipopolysaccharide. These data identify the
      proteasome as the primary degradation pathway for iNOS.

PMID- 11312271
TI  - Ca2+ binding to alpha-synuclein regulates ligand binding and oligomerization.
AB  - alpha-Synuclein is a protein normally involved in presynaptic vesicle
      homeostasis. It participates in the development of Parkinson's disease, in which
      the nerve cell lesions, Lewy bodies, accumulate alpha-synuclein filaments. The
      synaptic neurotransmitter release is primarily dependent on Ca(2+)-regulated
      processes. A microdialysis technique was applied showing that alpha-synuclein
      binds Ca(2+) with an IC(50) of about 2-300 microm and in a reaction uninhibited
      by a 50-fold excess of Mg(2+). The Ca(2+)-binding site consists of a novel C
      terminally localized acidic 32-amino acid domain also present in the homologue
      beta-synuclein, as shown by Ca(2+) binding to truncated recombinant and synthetic
      alpha-synuclein peptides. Ca(2+) binding affects the functional properties of
      alpha-synuclein. First, the ligand binding of (125)I-labeled bovine microtubule
      associated protein 1A is stimulated by Ca(2+) ions in the 1-500 microm range and
      is dependent on an intact Ca(2+) binding site in alpha-synuclein. Second, the
      Ca(2+) binding stimulates the proportion of (125)I-alpha-synuclein-containing
      oligomers. This suggests that Ca(2+) ions may both participate in normal alpha
      synuclein functions in the nerve terminal and exercise pathological effects
      involved in the formation of Lewy bodies.

PMID- 11312272
TI  - Emergence of multifunctional oxygenase activities by random priming
      recombination.
AB  - Biphenyl dioxygenase (Bph Dox) is responsible for the initial dioxygenation of
      biphenyl. The large subunit (BphA1) of Bph Dox plays a crucial role in
      determination of substrate specificity of biphenyl-related compounds including
      polychlorinated biphenyls (PCBs). Functional evolution of Bph Dox of Pseudomonas
      pseudoalcaligenes KF707 was accomplished by random priming recombination of the
      bphA1 gene, involving two rounds of in vitro recombination and mutation followed
      by selection for increased activity in vivo. Evolved Bph Dox acquired novel and
      multifunctional degradation capabilities not only for PCBs but also for
      dibenzofuran, dibenzo-p-dioxin, dibenzothiophene, and fluorene, the compounds
      scarcely attacked by the original KF707 Bph Dox. The modes of oxygenation were
      angular and lateral dioxygenation for dibenzofuran and dibenzo-p-dioxin,
      sulfoxidation for dibenzothiophene, and mono-oxygenation for fluorene. These
      enzymes also exhibited enhanced degradation abilities for PCB congeners,
      retaining 2,3-dioxygenase activity and gaining 3,4-dioxygenase activity,
      depending on the chlorine substitution of PCB congeners. Further mutation
      analysis revealed that the amino acid at position 376 in BphA1 is significantly
      involved in the acquisition of multifunctional oxygenase activities and mode of
      oxygenation.

PMID- 11312273
TI  - A dileucine motif targets E-cadherin to the basolateral cell surface in Madin
      Darby canine kidney and LLC-PK1 epithelial cells.
AB  - E-cadherin is a major adherens junction protein of epithelial cells, with a
      central role in cell-cell adhesion and cell polarity. Newly synthesized E
      cadherin is targeted to the basolateral cell surface. We analyzed targeting
      information in the cytoplasmic tail of E-cadherin by utilizing chimeras of E
      cadherin fused to the ectodomain of the interleukin-2alpha (IL-2alpha) receptor
      expressed in Madin-Darby canine kidney and LLC-PK(1) epithelial cells. Chimeras
      containing the full-length or membrane-proximal half of the E-cadherin
      cytoplasmic tail were correctly targeted to the basolateral domain. Sequence
      analysis of the membrane-proximal tail region revealed the presence of a highly
      conserved dileucine motif, which was analyzed as a putative targeting signal by
      mutagenesis. Elimination of this motif resulted in the loss of Tac/E-cadherin
      basolateral localization, pinpointing this dileucine signal as being both
      necessary and sufficient for basolateral targeting of E-cadherin. Truncation
      mutants unable to bind beta-catenin were correctly targeted, showing, contrary to
      current understanding, that beta-catenin is not required for basolateral
      trafficking. Our results also provide evidence that dileucine-mediated targeting
      is maintained in LLC-PK(1) cells despite the altered polarity of basolateral
      proteins with tyrosine-based signals in this cell line. These results provide the
      first direct insights into how E-cadherin is targeted to the basolateral
      membrane.

PMID- 11312274
TI  - A conserved Asn in transmembrane helix 7 is an on/off switch in the activation of
      the thyrotropin receptor.
AB  - The thyrotropin (TSH) receptor is an interesting model to study G protein-coupled
      receptor activation as many point mutations can significantly increase its basal
      activity. Here, we identified a molecular interaction between Asp(633) in
      transmembrane helix 6 (TM6) and Asn(674) in TM7 of the TSHr that is crucial to
      maintain the inactive state through conformational constraint of the Asn. We show
      that these residues are perfectly conserved in the glycohormone receptor family,
      except in one case, where they are exchanged, suggesting a direct interaction.
      Molecular modeling of the TSHr, based on the high resolution structure of
      rhodopsin, strongly favors this hypothesis. Our approach combining site-directed
      mutagenesis with molecular modeling shows that mutations disrupting this
      interaction, like the D633A mutation in TM6, lead to high constitutive
      activation. The strongly activating N674D (TM7) mutation, which in our modeling
      breaks the TM6-TM7 link, is reverted to wild type-like behavior by an additional
      D633N mutation (TM6), which would restore this link. Moreover, we show that the
      Asn of TM7 (conserved in most G protein-coupled receptors) is mandatory for
      ligand-induced cAMP accumulation, suggesting an active role of this residue in
      activation. In the TSHr, the conformation of this Asn residue of TM7 would be
      constrained, in the inactive state, by its Asp partner in TM6.

PMID- 11312275
TI  - The solution structure of the complex formed between alpha-bungarotoxin and an 18
      mer cognate peptide derived from the alpha 1 subunit of the nicotinic
      acetylcholine receptor from Torpedo californica.
AB  - The region encompassing residues 181-98 on the alpha1 subunit of the muscle-type
      nicotinic acetylcholine receptor forms a major determinant for the binding of
      alpha-neurotoxins. We have prepared an (15)N-enriched 18-amino acid peptide
      corresponding to the sequence in this region to facilitate structural elucidation
      by multidimensional NMR. Our aim was to determine the structural basis for the
      high affinity, stoichiometric complex formed between this cognate peptide and
      alpha-bungarotoxin, a long alpha-neurotoxin. Resonances in the complex were
      assigned through heteronuclear and homonuclear NMR experiments, and the resulting
      interproton distance constraints were used to generate ensemble structures of the
      complex. Thr(8), Pro(10), Lys(38), Val(39), Val(40), and Pro(69) in alpha
      bungarotoxin and Tyr(189), Tyr(190), Thr(191), Cys(192), Asp(195), and Thr(196)
      in the peptide participate in major intermolecular contacts. A comparison of the
      free and bound alpha-bungarotoxin structures reveals significant conformational
      rearrangements in flexible regions of alpha-bungarotoxin, mainly loops I, II, and
      the C-terminal tail. Furthermore, several of the calculated structures suggest
      that cation-pi interactions may be involved in binding. The root mean square
      deviation of the polypeptide backbone in the complex is 2.07 A. This structure
      provides, to date, the highest resolution description of the contacts between a
      prototypic alpha-neurotoxin and its cognate recognition sequence.

PMID- 11312276
TI  - How protein kinase C activation protects nerve cells from oxidative stress
      induced cell death.
AB  - Oxidative stress is implicated in the nerve cell death that occurs in a variety
      of neurological disorders, and the loss of protein kinase C (PKC) activity has
      been coupled to the severity of the damage. The functional relationship between
      stress, PKC, and cell death is, however, unknown. Using an immortalized
      hippocampal cell line that is particularly sensitive to oxidative stress, I show
      that activation of PKC by the phorbol ester tetradecanoylphorbol acetate (TPA)
      inhibits cell death via the stimulation of a complex protein phosphorylation
      pathway. TPA treatment leads to the rapid activation of extracellular signal
      regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), the inactivation of
      p38 mitogen-activated protein kinase (MAPK), and the downregulation of PKCdelta.
      Inhibition of either ERK or JNK activation blocks TPA-mediated protection,
      whereas p38 MAPK and PKCdelta inhibitors block stress-induced nerve cell death.
      Both p38 MAPK inactivation and JNK activation appear to be downstream of ERK
      because an agent that blocks ERK activation also blocks the modulation of these
      other MAP kinase family members by TPA treatment. Thus, the protection from
      oxidative stress afforded nerve cells by PKC activity requires the combined
      modulation of multiple enzyme pathways and suggests why the loss of PKC activity
      contributes to nerve cell death.

PMID- 11312277
TI  - Distinct molecular determinants govern syntaxin 1A-mediated inactivation and G
      protein inhibition of N-type calcium channels.
AB  - We have reported recently that syntaxin 1A mediates two effects on N-type
      channels transiently expressed in tsA-201 cells: a hyperpolarizing shift in the
      steady-state inactivation curve as well as a tonic inhibition of the channel by G
      protein betagamma subunits (Jarvis et al., 2000). Here we have examined some of
      the molecular determinants and factors that modulate the action of syntaxin 1A on
      N-type calcium channels. With the additional coexpression of SNAP25, the syntaxin
      1A-induced G-protein modulation of the channel became reduced in magnitude by
      approximately 50% but nonetheless remained significantly higher than the low
      levels of background inhibition seen with N-type channels alone. In contrast,
      coexpression of nSec-1 did not reduce the syntaxin 1A-mediated G-protein
      inhibition; however, interestingly, nSec-1 was able to induce tonic G-protein
      inhibition even in the absence of syntaxin 1A. Both SNAP25 and nSec-1 blocked the
      negative shift in half-inactivation potential that was induced by syntaxin 1A.
      Activation of protein kinase C via phorbol esters or site-directed mutagenesis of
      three putative PKC consensus sites in the syntaxin 1A binding region of the
      channel (S802, S896, S898) to glutamic acid (to mimic a permanently
      phosphorylated state) did not affect the syntaxin 1A-mediated G-protein
      modulation of the channel. However, in the S896E and S898E mutants, or after PKC
      dependent phosphorylation of the wild-type channels, the susceptibility of the
      channel to undergo shifts in half-inactivation potential was removed. Thus,
      separate molecular determinants govern the ability of syntaxin 1A to affect N
      type channel gating and its modulation by G-proteins.

PMID- 11312278
TI  - Syntaxin 1A supports voltage-dependent inhibition of alpha1B Ca2+ channels by
      Gbetagamma in chick sensory neurons.
AB  - N-type Ca(2+) channels are modulated by a variety of G-protein-coupled pathways.
      Some pathways produce a transient, voltage-dependent (VD) inhibition of N channel
      function and involve direct binding of G-protein subunits; others require the
      activation of intermediate enzymes and produce a longer-lasting, voltage
      independent (VI) form of inhibition. The ratio of VD:VI inhibition differs
      significantly among cell types, suggesting that the two forms of inhibition play
      unique physiological roles in the nervous system. In this study, we explored
      mechanisms capable of altering the balance of VD and VI inhibition in chick
      dorsal root ganglion neurons. We report that (1) VD:VI inhibition is critically
      dependent on the Gbetagamma concentration, with VI inhibition dominant at low
      Gbetagamma concentrations, and (2) syntaxin-1A (but not syntaxin-1B) shifts the
      ratio in favor of VD inhibition by potentiating the VD effects of Gbetagamma.
      Variations in expression levels of G-proteins and/or syntaxin provide the means
      to alter over a wide range both the extent and the rate of Ca(2+) influx through
      N channels.

PMID- 11312279
TI  - Kainate receptors depress excitatory synaptic transmission at CA3-->CA1 synapses
      in the hippocampus via a direct presynaptic action.
AB  - Kainate receptor activation depresses synaptic release of neurotransmitter at a
      number of synapses in the CNS. The mechanism underlying this depression is
      controversial, and both ionotropic and metabotropic mechanisms have been
      suggested. We report here that the AMPA/kainate receptor agonists domoate (DA)
      and kainate (KA) cause a presynaptic depression of glutamatergic transmission at
      CA3-->CA1 synapses in the hippocampus, which is not blocked by the AMPA receptor
      antagonist GYKI 53655 but is blocked by the AMPA/KA receptor antagonist CNQX.
      Neither a blockade of interneuronal discharge nor antagonists of several
      neuromodulators affect the depression, suggesting that it is not the result of
      indirect excitation and subsequent release of a neuromodulator. Presynaptic
      depolarization, achieved via increasing extracellular K(+), caused a depression
      of the presynaptic fiber volley and an increase in the frequency of miniature
      EPSCs. Neither effect was observed with DA, suggesting that DA does not depress
      transmission via a presynaptic depolarization. However, the effects of DA were
      abolished by the G-protein inhibitors N-ethylmaleimide and pertussis toxin. These
      results suggest that KA receptor activation depresses synaptic transmission at
      this synapse via a direct, presynaptic, metabotropic action.

PMID- 11312280
TI  - Protein kinase C-mediated inhibition of mu-opioid receptor internalization and
      its involvement in the development of acute tolerance to peripheral mu-agonist
      analgesia.
AB  - We investigated the role of protein kinase C (PKC) in cell mu-opioid receptor
      (MOR) internalization and MOR-mediated acute tolerance in vivo. When Chinese
      hamster ovary cells expressing MOR were exposed to [D-Ala(2),MePhe(4),Gly-ol(5)]
      enkephalin (DAMGO), receptor internalization was observed at 30 min. Incubation
      with morphine failed to induce receptor internalization. When calphostin C, a PKC
      inhibitor, was added, receptor internalization was observed as early as 10 min
      after morphine stimulation. The MOR internalization induced by DAMGO or morphine
      in the presence of calphostin C was dynamin dependent, because it was abolished 2
      d after pretreatment with recombinant adenovirus to express a dominant
      interfering dynamin mutant (K44A/dynamin adenovirus). On the other hand, in a
      peripheral nociception test in mice, the nociceptive flexor response after
      intraplantar injection (i.pl.) of bradykinin was markedly inhibited by DAMGO
      (i.pl.). DAMGO analgesia was not affected by 2 hr prior injection (i.pl.) of
      DAMGO. Marked acute tolerance was observed after pretreatment with dynamin
      antisense oligodeoxynucleotide or K44A/dynamin adenovirus. The DAMGO-induced
      acute tolerance under such pretreatments was inhibited by calphostin C. Together,
      these findings suggest that PKC desensitizes MOR or has a role in the development
      of acute tolerance through MOR by inhibiting internalization mechanisms as a
      resensitization process.

PMID- 11312281
TI  - Ionotropic histamine receptors and H2 receptors modulate supraoptic oxytocin
      neuronal excitability and dye coupling.
AB  - Histaminergic neurons of the tuberomammillary nucleus (TM) project
      monosynaptically to the supraoptic nucleus (SON). This projection remains intact
      in our hypothalamic slices and permits investigation of both brief synaptic
      responses and the effects of repetitively activating this pathway. SON oxytocin
      (OX) neurons respond to single TM stimuli with fast IPSPs, whose kinetics
      resemble those of GABA(A) or glycine receptors. IPSPs were blocked by the Cl(-)
      channel blocker picrotoxin, but not by bicuculline or strychnine, and by
      histamine H(2), but not by H(1) or H(3) receptor antagonists, suggesting the
      presence of an ionotropic histamine receptor and the possible nonspecificity of
      currently used H(2) antagonists. G-protein mediation of the IPSPs was ruled out
      using guanosine 5'-O-(2-thiodiphosphate) (GDP-betaS), pertussis toxin, and Rp
      adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPs), none of which
      blocked evoked IPSPs. We also investigated the effects of synaptically released
      histamine on dye coupling and neuronal excitability. One hundred seventy-three OX
      neurons were Lucifer yellow-injected in horizontal slices. Repetitive TM
      stimulation (10 Hz, 5-10 min) reduced coupling, an effect blocked by H(2), but
      not by H(1) or H(3), receptor antagonists. Because H(2) receptors are linked to
      activation of adenylyl cyclase, TM-stimulated reduction in coupling was blocked
      by GDP-betaS, pertussis toxin, and Rp-cAMPs and was mimicked by 8-bromo-cAMP, 3
      isobutyl-1-methylxanthine, and Sp-cAMP. Membrane potentials of OX and vasopressin
      neurons were hyperpolarized, accompanied by decreased conductances, in response
      to bath application of 8-bromo-cAMP but not the membrane-impermeable cAMP. These
      results suggest that synaptically released histamine, in addition to evoking fast
      IPSPs in OX cells, mediates a prolonged decrease in excitability and uncoupling
      of the neurons.

PMID- 11312282
TI  - Substance P abolishes the facilitatory effect of ATP on spontaneous glycine
      release in neurons of the trigeminal nucleus pars caudalis.
AB  - Glycine release was facilitated by the activation of presynaptic ATP receptors
      (P(2X)-type) in a preparation of dissociated trigeminal nucleus pars caudalis
      neurons in which the native synaptic boutons were preserved. The action of ATP
      was completely blocked by substance P (SP) without alteration of the miniature
      IPSC (mIPSC) amplitude distribution. SP itself had no effect on mIPSC frequency
      or amplitude. The inhibitory effect of SP on ATP action was blocked by CP99994,
      indicating that the SP receptors are of the neurokinin-1 type. The ATP-induced
      facilitation of the mIPSC frequency was unaffected by Cd(2+). Moreover, SP did
      not inhibit the increase in mIPSC frequency induced high K(+) application,
      suggesting that SP did not modulate voltage-dependent calcium channels or
      subsequent steps in the release process. KT5720 and phorbol 12-myristate 13
      acetate did not block SP action, indicating that neither the cAMP-protein kinase
      A nor the protein kinase C pathway mediates the SP effects. However, in the
      presence of N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7), SP was no
      longer able to inhibit the ATP-induced stimulation of mIPSC frequency. 1-[N,O
      bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine also
      suppressed the SP action, suggesting that SP modulates P(2X) receptors via a
      Ca(2+)/calmodulin-dependent protein kinase II-mediated pathway. In conventional
      whole-cell mode, the presence of W-7 in the patch pipette did not affect the SP
      inhibitory action. Thus, SP is not likely to be generating its modulation through
      the production of a retrograde signal (involving calmodulin) from the
      postsynaptic cell to the presynaptic boutons. These results are the first
      demonstration of the modulation of one presynaptic receptor by another. Because
      SP inhibits the ATP stimulation of glycine release, SP may play a significant
      role in hyperalgesia or chronic pain.

PMID- 11312283
TI  - Kainate receptors regulate unitary IPSCs elicited in pyramidal cells by fast
      spiking interneurons in the neocortex.
AB  - Unitary IPSCs elicited by fast-spiking (FS) interneurons in layer V pyramidal
      cells of the neocortex were studied by means of dual whole-cell recordings in
      acute slices. FS to pyramidal cell unitary IPSCs were depressed by (RS)-S-amino-3
      (3-hydroxy-5-tert-butylisoxazol-4-yl) (ATPA), a kainate (KA) receptor agonist,
      and by the endogenous agonist l-glutamate in the presence of AMPA, NMDA, mGluR,
      and GABA(B) receptor antagonists. This effect was accompanied by an increase in
      failure rate of synaptic transmission, in the coefficient of variation, and in
      the paired pulse ratio, indicating a presynaptic origin of the IPSC depression.
      Pairing the activation of the presynaptic neuron with a depolarization of the
      postsynaptic cell mimicked the decrease of unitary IPSCs, and this effect
      persisted when postsynaptic sodium action potentials were blocked with the local
      anesthetic QX314. The effects of ATPA, glutamate, and of the pairing protocol
      were almost totally blocked by CNQX. These data suggest that KA receptors located
      on presynaptic FS cell terminals decrease the release of GABA and can be
      activated by glutamate released from the somatodendritic compartment of the
      postsynaptic pyramidal cells.

PMID- 11312284
TI  - Rearrangement of nicotinic receptor alpha subunits during formation of the ligand
      binding sites.
AB  - Muscle nicotinic acetylcholine receptors (AChRs) are pentamers that contain two
      alpha subunits a beta, gamma (or epsilon), and delta subunit. In this paper, we
      have characterized subunit processing and folding events leading to formation of
      the two AChR ligand binding sites. alpha subunit residues, 187-199, which are
      part of overlapping ACh and alpha-bungarotoxin (Bgt) binding sites on AChRs, were
      assayed using a monoclonal antibody (mAb) specific for these residues. We found
      that this region was inaccessible to the mAb early during AChR assembly but
      became accessible as the first of two Bgt binding sites formed later during
      assembly, indicating that the region changes conformation as the Bgt binding site
      appears. Without previous reduction, 20% of the alpha subunits could be alkylated
      by bromoacetylcholine bromide as the first ACh binding site formed, which further
      indicated that the disulfide bond between cysteines 192 and 193 does not form
      until the first ACh binding site appears soon after Bgt binding site formation.
      When alpha subunits were mutated to add a glycosylation site at residue 187, the
      number of Bgt binding sites increased threefold, AChRs assembled more
      efficiently, and 2.5-fold more AChRs reached the cell surface. Our results
      indicate that binding site formation involves a rate-limiting rearrangement of
      the alpha subunit that exposes the 187-199 region to the endoplasmic reticulum
      lumen and determines when cysteines 192 and 193 disulfide bond.

PMID- 11312285
TI  - GABA(A) receptor alpha1 subunit deletion prevents developmental changes of
      inhibitory synaptic currents in cerebellar neurons.
AB  - Developmental changes in miniature IPSC (mIPSC) kinetics have been demonstrated
      previously in cerebellar neurons in rodents. We report that these kinetic changes
      in mice are determined primarily by developmental changes in GABA(A) receptor
      subunit expression. mIPSCs were studied by whole-cell recordings in cerebellar
      slices, prepared from postnatal day 11 (P11) and P35 mice. Similar to reports in
      granule neurons, wild-type cerebellar stellate neuron mIPSCs at P11 had slow
      decay kinetics, whereas P35 mIPSCs decayed five times faster. When mIPSCs in
      cerebellar stellate neurons were compared between wild-type (+/+) and GABA(A)
      receptor alpha1 subunit-deficient (-/-) littermates at P35, we observed
      dramatically slower mIPSC decay rates in -/- animals. We took advantage of the
      greater potency of imidazopyridines for GABA current potentiation with alpha1
      subunit-containing receptors to characterize the relative contribution of alpha1
      subunits in native receptors on inhibitory synapses of cerebellar granule
      neurons. Zolpidem-induced prolongation of mIPSC decay was variable among distinct
      cells, but it increased during development in wild-type mice. Similarly, Zolpidem
      prolongation of mIPSC decay rate was significantly greater in adult +/+ mice than
      in knock-outs. We propose that an increased alpha1 subunit assembly in
      postsynaptic receptors of cerebellar inhibitory synapses is responsible for the
      fast inhibitory synaptic currents that are normally observed during postnatal
      development.

PMID- 11312286
TI  - Mitochondrial abnormalities in Alzheimer's disease.
AB  - The finding that oxidative damage, including that to nucleic acids, in
      Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal
      populations suggests that mitochondrial abnormalities might be part of the
      spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we
      used in situ hybridization to mitochondrial DNA (mtDNA), immunocytochemistry of
      cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens
      to determine whether there are mitochondrial abnormalities in Alzheimer's disease
      and their relationship to oxidative damage marked by 8-hydroxyguanosine and
      nitrotyrosine. We found that the same neurons showing increased oxidative damage
      in Alzheimer's disease have a striking and significant increase in mtDNA and
      cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is
      found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated
      with lipofuscin. Morphometric analysis showed that mitochondria are significantly
      reduced in Alzheimer's disease. The relationship shown here between the site and
      extent of mitochondrial abnormalities and oxidative damage suggests an intimate
      and early association between these features in Alzheimer's disease.

PMID- 11312287
TI  - Neuroprotection mediated by glial cell line-derived neurotrophic factor:
      involvement of a reduction of NMDA-induced calcium influx by the mitogen
      activated protein kinase pathway.
AB  - The glial cell line-derived neurotrophic factor (GDNF) is first characterized for
      its trophic activity on dopaminergic neurons. Recent data suggested that GDNF
      could modulate the neuronal death induced by ischemia. The purpose of this study
      was to characterize the influence of GDNF on cultured cortical neurons subjected
      to two paradigms of injury (necrosis and apoptosis) that have been identified
      during cerebral ischemia and to determine the molecular mechanisms involved.
      First, we demonstrated that both neurons and astrocytes express the mRNA and the
      protein for GDNF and its receptor complex (GFRalpha-1 and c-Ret). Next, we showed
      that the application of recombinant human GDNF to cortical neurons and astrocytes
      induces the activation of the MAP kinase (MAPK) pathway, as visualized by an
      increase in the phosphorylated forms of extracellular signal-regulated kinases
      (ERKs). Thereafter, we demonstrated that GDNF fails to prevent apoptotic neuronal
      death but selectively attenuates slowly triggered NMDA-induced excitotoxic
      neuronal death via a direct effect on cortical neurons. To further characterize
      the neuroprotective mechanisms of GDNF against NMDA-mediated neuronal death, we
      showed that a pretreatment with GDNF reduces NMDA-induced calcium influx. This
      effect likely results from a reduction of NMDA receptor activity rather than an
      enhanced buffering or extrusion capacity for calcium. Finally, we also
      demonstrated that an ERKs activation pathway is necessary for GDNF-mediated
      reduction of the NMDA-induced calcium response. Together, these results describe
      a novel mechanism by which the activation of MAPK induced by GDNF modulates NMDA
      receptor activity, a mechanism that could be responsible for the neuroprotective
      effect of GDNF in acute brain injury.

PMID- 11312288
TI  - Drosophila stoned proteins regulate the rate and fidelity of synaptic vesicle
      internalization.
AB  - At an initial step during synaptic vesicle recycling, dynamin and adaptor
      proteins mediate the endocytosis of synaptic vesicle components from the plasma
      membrane. StonedA and stonedB, novel synaptic proteins encoded by a single
      Drosophila gene, have predicted structural similarities to adaptors and other
      proteins implicated in endocytosis. Here, we test possible roles of the stoned
      proteins in synaptic vesicle internalization via analyses of third instar larval
      neuromuscular synapses in two Drosophila stoned (stn) mutants, stn(ts) and
      stn(8P1). Both mutations reduce presynaptic levels of stonedA and stonedB,
      although stn(ts) has relatively weak effects. The mutations cause retention of
      synaptic vesicle proteins on the presynaptic plasma membrane but do not alter the
      levels or distribution of endocytosis proteins, dynamin, alpha-adaptin, and
      clathrin. In addition, stn(8P1) mutants exhibit depletion and enlargement of
      synaptic vesicles. To determine whether these defects arise from altered synaptic
      vesicle endocytosis or from defects in synaptic vesicle biogenesis, we
      implemented new methods to assess directly the efficiency of synaptic vesicle
      recycling and membrane internalization at Drosophila nerve terminals. Behavioral
      and electrophysiological analyses indicate that stn(ts), an allele with normal
      evoked release and synaptic vesicle number, enhances defects in synaptic vesicle
      recycling shown by Drosophila shi(ts) mutants. A dye uptake assay demonstrates
      that slow synaptic vesicle recycling in stn(ts) is accompanied by a reduced rate
      of synaptic vesicle internalization after exocytosis. These observations are
      consistent with a model in which stonedA and stonedB act to facilitate the
      internalization of synaptic vesicle components from the plasma membrane.

PMID- 11312289
TI  - A novel role of vasopressin in the brain: modulation of activity-dependent water
      flux in the neocortex.
AB  - The brain contains an intrinsic vasopressin fiber system the function of which is
      unknown. It has been demonstrated recently that astrocytes express high levels of
      a water channel, aquaporin-4 (AQP4). Because vasopressin is known to regulate
      aquaporin expression and translocation in kidney collecting ducts and thereby
      control water reabsorption, we hypothesized that vasopressin might serve a
      similar function in the brain. By recording intrinsic optical signals in an acute
      cortical slice preparation we showed that evoked neuronal activity generates a
      radial water flux in the neocortex. The rapid onset and high capacity of this
      flux suggest that it is mediated through the AQP4-containing astrocytic syncytium
      that spans the entire thickness of the neocortical mantle. Vasopressin and
      vasopressin receptor V1a agonists were found to facilitate this flux. V1a
      antagonists blocked the facilitatory effect of vasopressin and reduced the water
      flux even in the absence of any exogenous agonist. V2 agonists or antagonists had
      no effect. These data suggest that vasopressin and V1a receptors play a crucial
      role in the regulation of brain water and ion homeostasis, most probably by
      modulating aquaporin-mediated water flux through astrocyte plasma membranes.

PMID- 11312290
TI  - Identification of amino acid residues in GluR1 responsible for ligand binding and
      desensitization.
AB  - Although GluR1(o) and GluR3(o) are homologous at the amino acid level, GluR3(o)
      desensitizes approximately threefold faster than GluR1(o). By creating chimeras
      of GluR1(o) and GluR3(o) and point amino acid exchanges in their S2 regions, two
      residues were identified to be critical for GluR1(o) desensitization: Y716 and
      the R/G RNA-edited site, R757. With creation of the double-point mutant (Y716F,
      R757G)GluR1(o), complete exchange of the desensitization rate of GluR1(o) to that
      of GluR3(o) was obtained. In addition, both the potency and affinity of the
      subtype-selective agonist bromohomoibotenic acid were exchanged by the Y716F
      mutation. A model is proposed of the AMPA receptor binding site whereby a
      hydrogen-bonding matrix of water molecules plays an important role in determining
      both ligand affinity and receptor desensitization properties. Residues Y716 in
      GluR1 and F728 in GluR3 differentially interact with this matrix to affect the
      binding affinity of some ligands, providing the possibility of developing subtype
      selective compounds.

PMID- 11312291
TI  - An NMDA receptor ER retention signal regulated by phosphorylation and alternative
      splicing.
AB  - Formation of mature excitatory synapses requires the assembly and delivery of
      NMDA receptors to the neuronal plasma membrane. A key step in the trafficking of
      NMDA receptors to synapses is the exit of newly assembled receptors from the
      endoplasmic reticulum (ER). Here we report the identification of an RXR-type ER
      retention/retrieval motif in the C-terminal tail of the NMDA receptor subunit NR1
      that regulates receptor surface expression in heterologous cells and in neurons.
      In addition, we show that PKC phosphorylation and an alternatively spliced
      consensus type I PDZ-binding domain suppress ER retention. These results
      demonstrate a novel quality control function for alternatively spliced C-terminal
      domains of NR1 and implicate both phosphorylation and potential PDZ-mediated
      interactions in the trafficking of NMDA receptors through early stages of the
      secretory pathway.

PMID- 11312292
TI  - Lack of neurotrophin-4 causes selective structural and chemical deficits in
      sympathetic ganglia and their preganglionic innervation.
AB  - Neurotrophin-4 (NT-4) is perhaps the still most enigmatic member of the
      neurotrophin family. We show here that NT-4 is expressed in neurons of
      paravertebral and prevertebral sympathetic ganglia, i.e., the superior cervical
      (SCG), stellate (SG), and celiac (CG) ganglion. Mice deficient for NT-4 showed a
      significant reduction (20-30%) of preganglionic sympathetic neurons in the
      intermediolateral column (IML) of the thoracic spinal cord. In contrast, neuron
      numbers in the SCG, SG, and CG were unchanged. Numbers of axons in the thoracic
      sympathetic trunk (TST) connecting the SG with lower paravertebral ganglia were
      also reduced, whereas axon numbers in the cervical sympathetic trunk (CST) were
      unaltered. Axon losses in the TST were paralleled by losses of synaptic terminals
      on SG neurons visualized by electron microscopy. Furthermore, immunoreactivity
      for the synaptic vesicle antigen SV2 was clearly reduced in the SG and CG. Levels
      of catecholamines and tyrosine hydroxylase immunoreactivity were dramatically
      reduced in the SG and the CG but not in the SCG. Despite this severe phenotype in
      the sympathetic system, blood pressure levels were not reduced and displayed a
      pattern more typical of deficits in baroreceptor afferents. Numbers of IML
      neurons were unaltered at postnatal day 4, suggesting a postnatal requirement for
      their maintenance. In light of these and previous data, we hypothesize that NT-4
      provided by postganglionic sympathetic neurons is required for establishing
      and/or maintaining synapses of IML neurons on postganglionic cells. Impairment of
      synaptic connectivity may consequently reduce impulse flow, causing a reduction
      in transmitter synthesis in postganglionic neurons.

PMID- 11312293
TI  - PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for
      development or function of parallel fiber synapses in cerebellum.
AB  - Membrane-associated guanylate kinases (MAGUKs) are abundant postsynaptic density
      (PSD)-95/discs large/zona occludens-1 (PDZ)-containing proteins that can assemble
      receptors and associated signaling enzymes at sites of cell-cell contact,
      including synapses. PSD-93, a postsynaptic neuronal MAGUK, has three PDZ domains
      that can bind to specific ion channels, including NMDA delta2 type glutamate
      receptors, as well as Shaker and inward rectifier type K(+) channels, and can
      mediate clustering of these channels in heterologous cells. Genetic analyses of
      Drosophila show that MAGUKs play critical roles in synaptic development because
      mutations of discs large disrupt the subsynaptic reticulum and block postsynaptic
      clustering of Shaker K(+) channels. It is uncertain whether MAGUKs play an
      essential role in the development of central synapses. There are four neuronal
      MAGUKs with overlapping expression patterns in the mammalian brain; however, we
      find PSD-93 is the only MAGUK expressed in cerebellar Purkinje neurons.
      Therefore, we targeted disruption of PSD-93 in mouse. Despite the absence of
      MAGUK immunoreactivity in Purkinje neurons from the knock-outs, these mice have
      no structural or functional abnormality in cerebellum. Both the dendritic
      architecture and the postsynaptic localization of PSD-93 interacting proteins
      remain intact at light and electron microscopic levels in the knock-outs.
      Postsynaptic Purkinje cell responses, monosynaptic climbing fiber innervation,
      and cerebellar-dependent behaviors are also normal. Our data demonstrate that
      MAGUK proteins of the PSD-93/95 family are not essential for development of
      certain central synapses but may instead participate in specialized aspects of
      synaptic signaling and plasticity.

PMID- 11312294
TI  - The expression pattern of the cell cycle inhibitor p19(INK4d) by progenitor cells
      of the rat embryonic telencephalon and neonatal anterior subventricular zone.
AB  - In this study we investigated whether the pattern of expression of the cyclin
      dependent kinase inhibitor p19(INK4d) by the unique progenitor cells of the
      neonatal anterior subventricular zone (SVZa) can account for their ability to
      divide even though they express phenotypic characteristics of differentiated
      neurons. p19(INK4d) was chosen for analysis because it usually acts to block
      permanently the cell cycle at the G(1) phase. p19(INK4d) immunoreactivity and the
      incorporation of bromodeoxyuridine (BrdU) by SVZa cells were compared with that
      of the more typical progenitor cells of the prenatal telencephalic ventricular
      zone. In the developing telencephalon, p19(INK4d) is expressed by postmitotic
      cells and has a characteristic perinuclear distribution depending on the laminar
      position and state of differentiation of a cell. Moreover, the laminar-specific
      staining of the developing cerebral cortex revealed that the ventricular zone
      (VZ) is divided into p19(INK4d)(+) and p19(INK4d)(-) sublaminae, indicating that
      the VZ has a previously unrecognized level of functional organization.
      Furthermore, the rostral migratory stream, traversed by the SVZa-derived cells,
      exhibits an anterior(high)-posterior(low) gradient of p19(INK4d) expression. On
      the basis of the p19(INK4d) immunoreactivity and BrdU incorporation, SVZa-derived
      cells appear to exit and reenter the cell cycle successively. Thus, in contrast
      to telencephalic VZ cells, SVZa cells continue to undergo multiple rounds of
      division and differentiation before becoming postmitotic.

PMID- 11312295
TI  - Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by
      blocking caspase-3-like activity.
AB  - Interleukin-10 (IL-10) has been shown to reduce neuronal degeneration after CNS
      injury. However, the molecular mechanisms underlying the neuroprotective
      properties of this cytokine are still under investigation. Glutamate exacerbates
      secondary injury caused by trauma. Thus, we examined whether IL-10 prevents
      glutamate-mediated cell death. We used rat cerebellar granule cells in culture
      because these neurons undergo apoptosis upon exposure to toxic concentrations of
      glutamate (100-500 microm) or NMDA (300 microm). Pretreatment of cerebellar
      granule cells with IL-10 (1-50 ng/ml) elicited a dose- and time-dependent
      reduction of glutamate-induced excitotoxicity. Most importantly, IL-10 reduced
      the number of apoptotic cells when added to the cultures together or 1 hr after
      glutamate. Using patch-clamping and fluorescence Ca(2+) imaging techniques, we
      examined whether IL-10 prevents glutamate toxicity by blocking the function of
      NMDA channel. IL-10 failed to affect NMDA channel properties and to reduce NMDA
      mediated rise in intracellular Ca(2+). Thus, this cytokine appears to prevent
      glutamate toxicity by a mechanism unrelated to a blockade of NMDA receptor
      function. Various proteases, such as caspase-3, and transcription factors, such
      as nuclear factor kappaB (NF-kappaB), have been proposed to participate in
      glutamate-mediated apoptosis. Thus, we examined whether IL-10 modulates the
      activity of these apoptotic markers. IL-10 blocked both the glutamate-mediated
      induction of caspase-3 as well as NF-kappaB DNA binding activity, suggesting that
      the neuroprotective properties of IL-10 may rely on its ability to block the
      activity of proapoptotic proteins.

PMID- 11312296
TI  - A novel member of the Ig superfamily, turtle, is a CNS-specific protein required
      for coordinated motor control.
AB  - We describe here the cloning and functional characterization of a neural-specific
      novel member of the Ig superfamily, turtle (tutl), with a structure of five Ig C2
      type domains, two fibronectin type III domains, and one transmembrane region.
      Alternative splicing of the tutl gene produces at least four Tutl isoforms,
      including two transmembrane proteins and two secreted proteins, with primary
      structures closely related to a human brain protein (KIAA1355), the Deleted in
      Colorectal Cancer/Neogenin/Frazzled receptor family, and the Roundabout/Dutt1
      receptor family. An allelic series of tutl gene mutations resulted in recessive
      lethality to semilethality, indicating that the gene is essential. In contrast to
      other family members, tutl does not play a detectable role in axon pathfinding or
      nervous system morphogenesis. Likewise, basal synaptic transmission and
      locomotory movement are unaffected. However, tutl mutations cause striking
      movement defects exhibited in specific types of highly coordinated behavior.
      Specifically, tutl mutants display an abnormal response to tactile stimulation,
      the inability to regain an upright position from an inverted position (hence,
      "turtle"), and the inability to fly in adulthood. These phenotypes demonstrate
      that tutl plays an essential role in establishing a nervous system capable of
      executing coordinated motor output in complex behaviors.

PMID- 11312297
TI  - Fate of midbrain dopaminergic neurons controlled by the engrailed genes.
AB  - Deficiencies in neurotransmitter-specific cell groups in the midbrain result in
      prominent neural disorders, including Parkinson's disease, which is caused by the
      loss of dopaminergic neurons of the substantia nigra. We have investigated in
      mice the role of the engrailed homeodomain transcription factors, En-1 and En-2,
      in controlling the developmental fate of midbrain dopaminergic neurons. En-1 is
      highly expressed by essentially all dopaminergic neurons in the substantia nigra
      and ventral tegmentum, whereas En-2 is highly expressed by a subset of them.
      These neurons are generated and differentiate their dopaminergic phenotype in En
      1/En-2 double null mutants, but disappear soon thereafter. Use of an En-1/tau
      LacZ knock-in mouse as an autonomous marker for these neurons indicates that they
      are lost, rather than that they change their neurotransmitter phenotype. A single
      allele of En-1 on an En-2 null background is sufficient to produce a wild type
      like substantia nigra and ventral tegmentum, whereas in contrast a single allele
      of En-2 on an En-1 null background results in the survival of only a small
      proportion of these dopaminergic neurons, a finding that relates to the
      differential expression of En-1 and En-2. Additional findings indicate that En-1
      and En-2 regulate expression of alpha-synuclein, a gene that is genetically
      linked to Parkinson's disease. These findings show that the engrailed genes are
      expressed by midbrain dopaminergic neurons from their generation to adulthood but
      are not required for their specification. However, the engrailed genes control
      the survival of midbrain dopaminergic neurons in a gene dose-dependent manner.
      Our findings also suggest a link between engrailed and Parkinson's disease.

PMID- 11312298
TI  - Mobilization of calcium from intracellular stores, potentiation of
      neurotransmitter-induced calcium transients, and capacitative calcium entry by 4
      aminopyridine.
AB  - In this study we analyzed the effect of 4-aminopyridine (4-AP) on free cytosolic
      calcium concentration ([Ca(2+)](i)) in basal conditions, after stimulation with
      neurotransmitters, and during capacitative calcium entry. Using fura-2
      ratiometric calcium imaging, we found that 4-AP increased [Ca(2+)](i) in type I
      astrocytes, neurons, and in skeletal muscle cells. The [Ca(2+)](i) elevation
      induced by 4-AP was concentration-dependent and consisted of two phases: the
      first was dependent on intracellular calcium mobilization, and the second was
      dependent on extracellular calcium influx. 4-AP also increased the second
      messenger inositol trisphosphate in both neurons and astrocytes. In astrocytes, 4
      AP treatment potentiated the sustained phase of the [Ca(2+)](i) elevation induced
      by ATP and bradykinin. In addition, capacitative calcium entry was potentiated
      severalfold by 4-AP, in astrocytes and muscle cells but not in neurons. These
      effects of 4-AP were completely and promptly reversible. 4-AP blocked voltage
      sensitive K(+) currents in astrocytes. However, voltage-sensitive K(+) channel
      blockers inhibiting these currents did not affect agonist-induced calcium
      transients or capacitative calcium entry, indicating that 4-AP effects on
      [Ca(2+)](i) were not caused by the blockade of voltage-gated K(+) channels. We
      conclude that 4-AP is able to affect calcium homeostasis at multiple levels, from
      increasing basal [Ca(2+)](i) to potentiating capacitative calcium entry. The
      potentiation of capacitative calcium entry in astrocytes or muscle cells may
      explain some of the therapeutic activities of 4-AP as a neurotransmission
      enhancer.

PMID- 11312299
TI  - Motoneuron survival is enhanced in the absence of neuromuscular junction
      formation in embryos.
AB  - Approximately half of the motoneurons produced during development die before
      birth or shortly after birth. Although it is believed that survival depends on a
      restricted supply of a trophic sustenance produced by the synaptic target tissue
      (i.e., muscle), it is unclear whether synapse formation per se is involved in
      motoneuron survival. To address this issue, we counted cranial motoneurons in a
      set of mutant mice in which formation of neuromuscular junctions is dramatically
      impaired (i.e., null mutants for agrin, nerve-derived agrin, rapsyn, and MuSK).
      We demonstrate that in the absence of synaptogenesis, there is an 18-34% increase
      in motoneuron survival in the facial, trochlear, trigeminal motor, and
      hypoglossal nuclei; the highest survival occurred in the MuSK-deficient animals
      in which synapse formation is most severely compromised. There was no change in
      the size of the mutant motoneurons as compared with control animals, and the
      morphology of the mutant motoneurons appeared normal. We postulate that the
      increased axonal branching observed in these mutants leads to a facilitated
      "access" of the motoneurons to muscle-derived trophic factors at sites other than
      synapses or that inactivity increases the production of such factors. Finally, we
      examined motoneurons in double mutants of CNTFRalpha(-/-) (in which there is a
      partial loss of motoneurons) and MuSK(-/-) (in which there is an increased
      survival of motoneurons). The motoneuron numbers in the double mutants parallel
      those of the single MuSK-deficient mice, indicating that synapse disruption can
      even overcome the deleterious effect of CNTFRalpha ablation.

PMID- 11312300
TI  - Src, Fyn, and Yes are not required for neuromuscular synapse formation but are
      necessary for stabilization of agrin-induced clusters of acetylcholine receptors.
AB  - Mice deficient in src and fyn or src and yes move and breathe poorly and die
      perinatally, consistent with defects in neuromuscular function. Src and Fyn are
      associated with acetylcholine receptors (AChRs) in muscle cells, and Src and Yes
      can act downstream of ErbB2, suggesting roles for Src family kinases in signaling
      pathways regulating neuromuscular synapse formation. We studied neuromuscular
      synapses in src(-/-); fyn(-/-) and src(-/-); yes(-/-) mutant mice and found that
      muscle development, motor axon pathfinding, clustering of postsynaptic proteins,
      and synapse-specific transcription are normal in these double mutants, showing
      that these pairs of kinases are not required for early steps in synapse
      formation. We generated muscle cell lines lacking src and fyn and found that
      neural agrin and laminin-1 induced normal clustering of AChRs and that agrin
      induced normal tyrosine phosphorylation of the AChR beta subunit in the absence
      of Src and Fyn. Another Src family member, most likely Yes, was associated with
      AChRs and phosphorylated by agrin in myotubes lacking Src and Fyn, indicating
      that Yes may compensate for the loss of Src and Fyn. Nevertheless, PP1 and PP2,
      inhibitors of Src-class kinases, did not inhibit agrin signaling, suggesting that
      Src class kinase activity is dispensable for agrin-induced clustering and
      tyrosine phosphorylation of AChRs. AChR clusters, however, were less stable in
      myotubes lacking Src and Fyn but not in PP1- or PP2-treated wild-type cells.
      These data show that the stabilization of agrin-induced AChR clusters requires
      Src and Fyn and suggest that the adaptor activities, rather than the kinase
      activities, of these kinases are essential for this stabilization.

PMID- 11312301
TI  - Adaptive axonal remodeling in the midbrain auditory space map.
AB  - The auditory space map in the external nucleus of the inferior colliculus (ICX)
      of barn owls is highly plastic, especially during early life. When juvenile owls
      are reared with prismatic spectacles (prisms) that displace the visual field
      laterally, the auditory spatial tuning of neurons in the ICX adjusts adaptively
      to match the visual displacement. In the present study, we show that this
      functional plasticity is accompanied by axonal remodeling. The ICX receives
      auditory input from the central nucleus of the inferior colliculus (ICC) via
      topographic axonal projections. We used the anterograde tracer biocytin to study
      experience-dependent changes in the spatial pattern of axons projecting from the
      ICC to the ICX. The projection fields in normal adults were sparser and more
      restricted than those in normal juveniles. The projection fields in prism-reared
      adults were denser and broader than those in normal adults and contained
      substantially more bouton-laden axons that were appropriately positioned in the
      ICX to convey adaptive auditory spatial information. Quantitative comparison of
      results from juvenile and prism-reared owls indicated that prism experience led
      to topographically appropriate axonal sprouting and synaptogenesis. We conclude
      that this elaboration of axons represents the formation of an adaptive neuronal
      circuit. The density of axons and boutons in the normal projection zone was
      preserved in prism-reared owls. The coexistence of two different circuits
      encoding alternative maps of space may underlie the ability of prism-reared owls
      to readapt to normal conditions as adults.

PMID- 11312302
TI  - Gating of human theta oscillations by a working memory task.
AB  - Electrode grids on the cortical surface of epileptic patients provide a unique
      opportunity to observe brain activity with high temporal-spatial resolution and
      high signal-to-noise ratio during a cognitive task. Previous work showed that
      large-amplitude theta frequency oscillations occurred intermittently during a
      maze navigation task, but it was unclear whether theta related to the spatial or
      working memory components of the task. To determine whether theta occurs during a
      nonspatial task, we made recordings while subjects performed the Sternberg
      working memory task. Our results show event-related theta and reveal a new
      phenomenon, the cognitive "gating" of a brain oscillation: at many cortical
      sites, the amplitude of theta oscillations increased dramatically at the start of
      the trial, continued through all phases of the trial, including the delay period,
      and decreased sharply at the end. Gating could be seen in individual trials and
      varying the duration of the trial systematically varied the period of gating.
      These results suggest that theta oscillations could have an important role in
      organizing multi-item working memory.

PMID- 11312303
TI  - Disruption of layers 3 and 4 during development results in altered
      thalamocortical projections in ferret somatosensory cortex.
AB  - The precision of projections from dorsal thalamus to neocortex are key toward
      understanding overall cortical organization and function. To identify the
      significance of layer 4 cells in receiving the bulk of thalamic projections in
      somatosensory cortex, we disrupted layer 4 genesis and studied the effect on
      thalamic terminations in ferrets. Second, we ascertained the result of layer 4
      disruption on functional responses and topographic organization. Methylazoxy
      methanol (MAM) was injected into pregnant ferrets on embryonic day 33 (E33), when
      most layer 4 neurons of somatosensory cortex are generated. This treatment
      resulted in dramatic reduction in the thickness of targeted layer 4. E38 MAM
      treatment was used as a control, when layer 2-3 neurons are generated. The
      projections of ventrobasal thalamus into somatosensory cortex were studied using
      DiI injections. We found only subtle differences between groups (normal, E33, or
      E38 MAM-treated) in the thalamic afferent pattern on postnatal day 1 (P1) and P7.
      On P14, thalamic terminations distribute almost equally throughout the remaining
      cortical layers in the E33 MAM-treated group compared with normal and E38 MAM
      treated animals, in which the ventrobasal thalamus projects primarily to central
      layers. Electrophysiological recordings conducted on mature ferrets treated with
      MAM on E33 demonstrated that somatotopic organization and receptive field size
      are normal. These findings emphasize the importance of layer 4 in determining the
      normal laminar pattern of thalamic termination and suggest that, although its
      absence is likely to impact on complex neocortical functional responses,
      topographic organization does not arise from the influence of layer 4.

PMID- 11312304
TI  - Reconstruction of target speed for the guidance of pursuit eye movements.
AB  - We studied how object speed is reconstructed from the responses of motion
      selective cells for the generation of a behavior that is tightly linked to the
      speed of visual motion. In theory, the speed of an object could be estimated
      either from the speed tuning of the active population of motion-selective cells
      or from the rate of displacement of activation across the cortical map of visual
      space. We measured the pursuit eye movements evoked by stimuli containing two
      conflicting motion components: a local component designed to excite motion
      selective cells with a particular speed tuning and a displacement component
      designed to excite cells with a sequence of spatial receptive fields. Pursuit eye
      movements were driven primarily by the local-motion component and were affected
      to only a small degree by the rate of target displacement across visual space.
      Extracellular single-unit recordings using the same stimuli revealed that the
      responses of cells in the middle temporal visual area (MT) depended primarily on
      the local-motion component but were influenced by the displacement component to
      the same degree as were pursuit eye movements. We conclude that the initiation of
      pursuit is consistent with a reconstruction of target speed based on the speed
      tuning of the active population of MT cells.

PMID- 11312305
TI  - Anxiolytic and anti-stress effects of brain prolactin: improved efficacy of
      antisense targeting of the prolactin receptor by molecular modeling.
AB  - We provide the first evidence that prolactin is a neuromodulator of behavioral
      and neuroendocrine stress coping in the rat. In virgin female and male rats,
      intracerebral infusion of ovine prolactin (oPRL) into the lateral cerebral
      ventricle (intracerebroventricular) exerted an anxiolytic effect on the elevated
      plus-maze in a dose-dependent manner (0.1 and 1.0 microg/5 microl; p < 0.01). In
      contrast, downregulation of the expression of the long form of brain prolactin
      receptors by chronic intracerebroventricular infusion of an antisense
      oligodeoxynucleotide (ODN) (osmotic minipump, 0.5 microg. 0.5 microl(-1). hr(-1);
      5 d) increased anxiety-related behavior on the plus-maze compared with mixed
      bases-treated and vehicle-treated rats (p < 0.01), again demonstrating an
      anxiolytic effect of PRL acting at brain level. Furthermore, in jugular vein
      catheterized female rats, the stress-induced increase of corticotropin secretion
      was decreased after chronic intracerebroventricular infusion of oPRL (osmotic
      minipump, 1.0 microg. 0.5 microl(-1). hr(-1); p < 0.05) and, in contrast, was
      further elevated by antisense targeting of the brain prolactin receptors (p <
      0.01). This provides evidence for a receptor-mediated attenuation of the
      responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis by prolactin. The
      antisense ODN sequence was selected on the basis of secondary structure molecular
      modeling of the target mRNA to improve antisense ODN-mRNA hybridization. Receptor
      autoradiography confirmed the expected improvement in the efficacy of
      downregulation of prolactin receptor expression [empirically designed antisense,
      30%; p > 0.05, not significant; adjustment of target position after mRNA
      modeling, 72%; p < 0.05). Taken together, prolactin acting at brain level has to
      be considered as a novel regulator of both emotionality and HPA axis reactivity.

PMID- 11312306
TI  - Representation of acoustic communication signals by insect auditory receptor
      neurons.
AB  - Despite their simple auditory systems, some insect species recognize certain
      temporal aspects of acoustic stimuli with an acuity equal to that of vertebrates;
      however, the underlying neural mechanisms and coding schemes are only partially
      understood. In this study, we analyze the response characteristics of the
      peripheral auditory system of grasshoppers with special emphasis on the
      representation of species-specific communication signals. We use both natural
      calling songs and artificial random stimuli designed to focus on two low-order
      statistical properties of the songs: their typical time scales and the
      distribution of their modulation amplitudes. Based on stimulus reconstruction
      techniques and quantified within an information-theoretic framework, our data
      show that artificial stimuli with typical time scales of >40 msec can be read
      from single spike trains with high accuracy. Faster stimulus variations can be
      reconstructed only for behaviorally relevant amplitude distributions. The highest
      rates of information transmission (180 bits/sec) and the highest coding
      efficiencies (40%) are obtained for stimuli that capture both the time scales and
      amplitude distributions of natural songs. Use of multiple spike trains
      significantly improves the reconstruction of stimuli that vary on time scales <40
      msec or feature amplitude distributions as occur when several grasshopper songs
      overlap. Signal-to-noise ratios obtained from the reconstructions of natural
      songs do not exceed those obtained from artificial stimuli with the same low
      order statistical properties. We conclude that auditory receptor neurons are
      optimized to extract both the time scales and the amplitude distribution of
      natural songs. They are not optimized, however, to extract higher-order
      statistical properties of the song-specific rhythmic patterns.

PMID- 11312307
TI  - 3,4-methylenedioxymethamphetamine (ecstasy)-induced learning and memory
      impairments depend on the age of exposure during early development.
AB  - Use of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has increased
      dramatically in recent years, yet little is known about its effects on the
      developing brain. Neonatal rats were administered MDMA on days 1-10 or 11-20
      (analogous to early and late human third trimester brain development). MDMA
      exposure had no effect on survival but did affect body weight gain during
      treatment. After treatment, body weight largely recovered to 90-95% of controls.
      MDMA exposure on days 11-20 resulted in dose-related impairments of sequential
      learning and spatial learning and memory, whereas neonatal rats exposed on days 1
      10 showed almost no effects. At neither stage of exposure did MDMA-treated
      offspring show effects on swimming ability or cued learning. Brain region
      specific dopamine, serotonin, and norepinephrine changes were small and were not
      correlated to learning changes. These findings suggest that MDMA may pose a
      previously unrecognized risk to the developing brain by inducing long-term
      deleterious effects on learning and memory.

PMID- 11312308
TI  - The role of dopamine in the nucleus accumbens and striatum during sexual behavior
      in the female rat.
AB  - Dopamine in dialysate from the nucleus accumbens (NAcc) increases during sexual
      and feeding behavior and after administration of drugs of abuse, even those that
      do not directly activate dopaminergic systems (e.g., morphine or nicotine). These
      findings and others have led to hypotheses that propose that dopamine is
      rewarding, predicts that reinforcement will occur, or attributes incentive
      salience. Examining increases in dopamine in NAcc or striatum during sexual
      behavior in female rats provides a unique situation to study these relations.
      This is because, for the female rat, sexual behavior is associated with an
      increase in NAcc dopamine and conditioned place preference only under certain
      testing conditions. This experiment was conducted to determine what factors are
      important for the increase in dopamine in dialysate from NAcc and striatum during
      sexual behavior in female rats. The factors considered were the number of
      contacts by the male, the timing of contacts by the male, or the ability of the
      female to control contacts by the male. The results indicate that increased NAcc
      dopamine is dependent on the timing of copulatory stimuli, independent of whether
      the female rat is actively engaged in regulating this timing. For the striatum,
      the timing of copulatory behavior influences the magnitude of the increase in
      dopamine in dialysate, but other factors are also involved. We conclude that
      increased extracellular dopamine in the NAcc and striatum conveys qualitative or
      interpretive information about the rewarding value of stimuli. Sexual behavior in
      the female rat is proposed as a model to determine the role of dopamine in
      motivated behavior.

PMID- 11312309
TI  - Preferential cytoplasmic localization of delta-opioid receptors in rat striatal
      patches: comparison with plasmalemmal mu-opioid receptors.
AB  - The activation of delta-opioid receptors (DORs) in the caudate-putamen nucleus
      (CPN) produces regionally distinct changes in motor functions, many of which are
      also influenced by opioids active at micro-opioid receptors (MORs). These actions
      most likely occur in MOR-enriched patch compartments in the CPN. To determine the
      functional sites for DOR activation and potential interactions involving MOR in
      these regions, immunoperoxidase and immunogold-silver labeling methods were
      applied reversibly for the ultrastructural localization of DOR and MOR in single
      rat brain sections containing patches of the CPN. DOR immunoreactivity was
      commonly seen within the cytoplasm of spiny and aspiny neurons, many of which
      also expressed MOR. In dendrites and spines, DOR labeling was preferentially
      localized to membranes of the smooth endoplasmic reticulum and spine apparatus,
      whereas MOR showed a prominent plasmalemmal distribution. DOR- and/or MOR-labeled
      spines received asymmetric, excitatory synapses, some of which showed notable
      perforations, suggesting the involvement of these receptors in activity-dependent
      synaptic plasticity. DORs were more frequently detected than were MORs within
      axon terminals that formed either asymmetric synapses with spine heads or
      symmetric synapses with spine necks. Our results suggest that in striatal
      patches, DORs, often in cooperation with MORs, play a direct modulatory role in
      controlling the postsynaptic excitability of spines, whereas presynaptic
      neurotransmitter release onto spines is mainly influenced by DOR activation. In
      comparison with MOR, the prevalent association of DOR with cytoplasmic organelles
      that are involved in intracellular trafficking of cell surface proteins suggests
      major differences in availability of these receptors to extracellular opioids.

PMID- 11312310
TI  - The role of the nucleus accumbens in instrumental conditioning: Evidence of a
      functional dissociation between accumbens core and shell.
AB  - In three experiments we examined the effect of bilateral excitotoxic lesions of
      the nucleus accumbens core or shell subregions on instrumental performance,
      outcome devaluation, degradation of the instrumental contingency, Pavlovian
      conditioning, and Pavlovian-instrumental transfer. Rats were food deprived and
      trained to press two levers, one delivering food pellets and the other a sucrose
      solution. All animals acquired the lever-press response although the rate of
      acquisition and overall response rates in core-lesioned animals were depressed
      relative to that in the shell- or sham-lesioned animals. Furthermore, in shell-
      and sham-lesioned rats, post-training devaluation of one of the two outcomes
      using a specific satiety procedure produced a selective reduction in performance
      on the lever that, in training, delivered the prefed outcome. In contrast, the
      core-lesioned rats failed to show a selective devaluation effect and reduced
      responding on both levers. Subsequent tests revealed that these effects of core
      lesions were not caused by an impairment in their ability to recall the devalued
      outcome, to discriminate the two outcomes, or to encode the instrumental action
      outcome contingencies to which they were exposed. Additionally, the core lesions
      did not have any marked effect on Pavlovian conditioning or on Pavlovian
      instrumental transfer. Importantly, although shell-lesioned rats showed no
      deficit in any test of instrumental conditioning or in Pavlovian conditioning,
      they failed to show any positive transfer in the Pavlovian-instrumental transfer
      test. This double dissociation suggests that nucleus accumbens core and shell
      differentially mediate the impact of instrumental and Pavlovian incentive
      processes, respectively, on instrumental performance.

PMID- 11312311
TI  - Fear and feeding in the nucleus accumbens shell: rostrocaudal segregation of GABA
      elicited defensive behavior versus eating behavior.
AB  - This study examined localization of positive versus negative motivational
      functions mediated by GABA circuits within the accumbens shell. Microinjections
      of a GABA(A) agonist (0, 25, 75, and 225 ng/0.5 microl muscimol) in rostral shell
      sites elicited appetitive increases in eating behavior. In contrast,
      microinjections in caudal shell sites elicited defensive burying or paw-treading
      behavior. Rats whose microinjections landed bilaterally outside of the accumbens
      shell did not display either behavior. Defensive treading elicited by caudal
      shell muscimol microinjection appeared to be a negative motivated response to
      threat (similar in parameters and orientation to normal defensive burying of a
      threatening electrified shock prod). The nucleus accumbens shell thus appears
      functionally heterogeneous in coding motivational valence. The demonstration that
      muscimol elicits positive eating behavior from rostral shell versus negative
      defensive behavior from caudal shell suggests in particular that GABAergic
      substrates of positive and negative types of motivated behavior in the nucleus
      accumbens shell are segregated along a rostrocaudal gradient.

PMID- 11312312
TI  - Medial geniculate, amygdalar and cingulate cortical training-induced neuronal
      activity during discriminative avoidance learning in rabbits with auditory
      cortical lesions.
AB  - This study addressed the neural mediation of discriminative avoidance learning,
      wherein rabbits step in a wheel apparatus in response to an acoustic conditional
      stimulus, the CS+, to avoid a foot shock, and they learn to ignore a different
      stimulus, the CS-, not followed by foot shock. Previously, muscimol-induced
      inactivation of the amygdala in the first session of training prevented learning
      during the inactivation and permanently blocked the development of discriminative
      training-induced neuronal activity (TIA) in the medial division of the medial
      geniculate nucleus (MGm). These results suggested that amygdalar neurons induce
      discriminative TIA in the MGm via basolateral (BL) amygdalar axonal projections
      to the auditory cortex. To test this hypothesis, the activity of neurons in the
      MGm was recorded during learning in rabbits with lesions of the auditory cortex.
      Recordings were also made in the lateral and BL amygdalar nuclei and in the
      cingulate cortex. In support of the hypothesis, discriminative learning in
      rabbits with lesions was impaired significantly during early training sessions 1
      4; in these same sessions, discriminative TIA was abolished in the MGm, the BL
      nucleus, and the anterior cingulate cortex. The lesions also blocked posterior
      cingulate cortical discriminative TIA in training sessions 1-2 but spared TIA in
      sessions 3-7. Lateral amygdalar neurons showed gradual development of
      discrimination that was not significantly affected by the lesions. The results
      demonstrate a critical role of auditory cortex in early discriminative learning
      and in the production of early discriminative TIA in multiple areas.

PMID- 11312313
TI  - Long-lasting reconfiguration of two interacting networks by a cooperation of
      presynaptic and postsynaptic plasticity.
AB  - The functional reconfiguration of central neuronal networks, a phenomenon by
      which neurons change their participation in network operation, is important for
      organizing adaptive behaviors. Such reconfiguration can be expressed in a long
      lasting manner (hours, days) after a training paradigm. The present study shows
      that such a long-lasting network reconfiguration requires a cooperation of both
      presynaptic and postsynaptic modifications in a neuronal interaction between two
      functionally distinct networks. In isolated preparations of the lobster
      stomatogastric nervous system, the single ventral dilator (VD) neuron can switch
      its functional participation from one discrete network (the pyloric network) to
      another (the cardiac sac network). This switching capability can be long-lasting
      and can be induced by a sensitizing procedure. A persistent change that was
      associated with this neuronal switching was found in each of the two networks.
      First, the intrinsic membrane properties of the VD neuron that allow it to
      participate spontaneously in the pyloric network are altered. Second, bursting
      activity is strengthened in the inferior ventricular neurons that both drive
      cardiac sac network activity and monosynaptically excite the VD neuron in phase
      with this network activity. Importantly, these changes in intrinsic properties of
      both presynaptic and postsynaptic neurons are required to allow the VD neuron
      switching, because expression of either the presynaptic or the postsynaptic
      change alone did not permit VD neuron switching to occur. These results suggest
      that a cooperative modification of a discrete network interaction is able to
      persistently switch the output pattern of a motor neuron as a result of a
      sensitizing paradigm.

PMID- 11312314
TI  - Excitatory nicotinic and desensitizing muscarinic (M2) effects on C-nociceptors
      in isolated rat skin.
AB  - The actions of different cholinergic agonists and antagonists were investigated
      on nociceptive afferents using the rat skin-saphenous nerve preparation, in
      vitro. Nicotine was able to weakly excite C-nociceptors and to induce a mild
      sensitization to heat stimulation (in 77% of tested fibers) in a dose-dependent
      manner (10(-)6 to 10(-)5 m), but it caused no alteration in mechanical
      responsiveness tested with von Frey hairs. Muscarine did not induce a significant
      nociceptor excitation, but almost all fibers exhibited a marked desensitization
      to mechanical and heat stimuli in a dose-dependent manner (from 10(-)6 to 10(-)4
      m). The muscarinic effects could be prevented by the general muscarinic
      antagonist scopolamine (10(-)5 m), by the M3 antagonist 1,1-dimethyl-4
      diphenylacetoxypiperidium oxide (10(-)6 m) co-applied with the M2 antagonist
      gallamine (10(-)5 m), and by gallamine alone. As positive control we used the
      relatively M2-selective agonist arecaidine (10(-)6 to 10(-)5 m), obtaining a
      similar desensitizing effect as with muscarine. Finally, we performed an
      immunocytochemical study that demonstrated the presence of M2 but not M3
      receptors in thin epidermal nerve fibers of the rat hairy skin. Altogether, these
      data demonstrate opposite effects of nicotinic and muscarinic receptor
      stimulation on cutaneous nociceptors. M2 receptor-mediated depression of
      nociceptive responsiveness may convey a therapeutic, i.e., analgesic or
      antinociceptive, potential.

PMID- 11312315
TI  - Cocaine and amphetamine increase extracellular dopamine in the nucleus accumbens
      of mice lacking the dopamine transporter gene.
AB  - Behavioral and biochemical studies suggest that dopamine (DA) plays a role in the
      reinforcing and addictive properties of drugs of abuse. Recently, this hypothesis
      has been challenged on the basis of the observation that, in mice genetically
      lacking the plasma membrane dopamine transporter [DAT-knock out (DAT-KO)],
      cocaine maintained its reinforcing properties of being self-administered and
      inducing place preference, despite the failure to increase extracellular dopamine
      in the dorsal striatum. Here we report that, in DAT-KO mice, cocaine and
      amphetamine increase dialysate dopamine in the medial part of the nucleus
      accumbens. Moreover, reboxetine, a specific blocker of the noradrenaline
      transporter, increased DA in the nucleus accumbens of DAT-KO but not of wild-type
      mice; in contrast, GBR 12909, a specific blocker of the dopamine transporter,
      increased dialysate dopamine in the nucleus accumbens of wild-type but not of DAT
      KO mice. These observations provide an explanation for the persistence of cocaine
      reinforcement in DAT-KO mice and support the hypothesis of a primary role of
      nucleus accumbens dopamine in drug reinforcement.

PMID- 11312316
TI  - A spatial hearing deficit in early-blind humans.
AB  - An important issue in neuroscience is the effect of visual loss on the remaining
      senses. Two opposing views have been advanced. On the one hand, visual loss may
      lead to compensatory plasticity and sharpening of the remaining senses. On the
      other hand, early blindness may also prevent remaining sensory modalities from a
      full development. In the case of sound localization, it has been reported
      recently that, under certain conditions, early-blind humans can localize sounds
      better than sighted controls. However, these studies were confined to a single
      sound source in the horizontal plane. This study compares sound localization of
      early-blind and sighted subjects in both the horizontal and vertical domain,
      whereas background noise was added to test more complex hearing conditions. The
      data show that for high signal-to-noise (S/N) ratios, localization by blind and
      sighted subjects is similar for both azimuth and elevation. At decreasing S/N
      ratios, the accuracy of the elevation response components deteriorated earlier
      than the accuracy of the azimuth component in both subject groups. However,
      although azimuth performance was identical for the two groups, elevation accuracy
      deteriorated much earlier in the blind subject group. These results indicate that
      auditory hypercompensation in early-blind humans does not extend to the frontal
      target domain, where the potential benefit of vision is maximal. Moreover, the
      results demonstrate for the first time that in this domain the human auditory
      system may require vision to optimally calibrate the elevation-related spectral
      pinna cues. Sensitivity to azimuth-encoding binaural difference cues, however,
      may be adequately calibrated in the absence of vision.

PMID- 11312317
TI  - Herpesvirus lytic replication and the cell cycle: arresting new developments.

PMID- 11312318
TI  - Cell cycle analysis of Epstein-Barr virus-infected cells following treatment with
      lytic cycle-inducing agents.
AB  - While Epstein-Barr virus (EBV) latency-associated gene expression is associated
      with cell cycle progression, the relationship between the EBV lytic program and
      the cell cycle is less clear. Using four different EBV lytic induction systems,
      we address the relationship between lytic cycle activation and the cell cycle. In
      three of these systems, G0 or G1 cell growth arrest signaling is observed prior
      to detection of the EBV immediate-early gene product Zta. In tetradecanoyl
      phorbol acetate-treated P3HR1 cultures and in 5-iodo-2'-deoxyuridine-treated NPC
      KT cultures, cell cycle analysis of Zta-expressing cell populations showed a
      significant G1 bias during the early stages of lytic cycle progression. In
      contrast, treatment of the cell line Akata with anti-immunoglobulin (Ig) results
      in rapid induction of immediate-early gene expression, and accordingly,
      activation of the immediate-early gene product Zta precedes significant anti-Ig
      induced cell cycle effects. Nevertheless, cell cycle analysis of the Zta
      expressing population following anti-Ig treatment shows a bias for cells in G1,
      indicating that anti-Ig-mediated induction of Zta occurs more efficiently in
      cells traversing G1. Last, although 5-azacytidine treatment of Rael cells results
      in a G1 arrest in the total cell population which precedes the induction of Zta,
      cell cycle analysis of the Zta-expressing population shows a significant bias for
      cells with an apparent G2/M DNA content. This bias may result, in part, from
      activation of Zta expression following demethylation of the Zta promoter during S
      phase. Together, these studies indicate that induction of Zta occurs through
      several distinct mechanisms, some of which may involve checkpoint signaling.

PMID- 11312319
TI  - Mus cervicolor murine leukemia virus isolate M813 belongs to a unique receptor
      interference group.
AB  - Murine leukemia virus (MuLV) M813 was originally isolated from the Southeast
      Asian rodent Mus cervicolor. As with the ecotropic MuLVs derived from Mus
      musculus, its host range is limited to rodent cells. Earlier studies have mapped
      its receptor to chromosome 2, but it has not been established whether M813 shares
      a common receptor with any other MuLVs. In this study, we have performed
      interference assays with M813 and viruses from four interference groups of MuLV.
      The infection efficiency of M813 was not compromised in cells expressing any one
      of the other MuLVs, demonstrating that M813 must use a distinct receptor for cell
      entry. The entire M813 env coding region was molecularly cloned. Sequence
      analysis revealed high similarity with other MuLVs but with a unique receptor
      binding domain. Substitution of M813 env sequences in Moloney MuLV resulted in a
      replication-competent virus with a host range and interference profile similar to
      those of the biological clone M813. M813 thus defines a novel receptor
      interference group of type C MuLVs.

PMID- 11312320
TI  - CD150 (SLAM) is a receptor for measles virus but is not involved in viral contact
      mediated proliferation inhibition.
AB  - Measles virus (MV) interacts with cellular receptors on the surface of peripheral
      blood lymphocytes (PBL) which mediate virus binding and uptake. Simultaneously,
      the direct contact of the viral glycoproteins with the cell surface induces a
      negative signal blocking progression to the S phase of the cell cycle, resulting
      in a pronounced proliferation inhibition. We selected a monoclonal antibody (MAb
      5C6) directed to the surface of highly MV-susceptible B cells (B95a), which
      inhibits binding to and infection of cells with MV wild-type and vaccine strains.
      By screening a retroviral cDNA library from human splenocytes (ViraPort;
      Stratagene) with this antibody, we cloned and identified the recognized molecule
      as signaling lymphocytic activation molecule (SLAM; CD150), which is identical to
      the MV receptor recently found by H. Tatsuo et al. (Nature 406:893-897, 2000).
      After infection of cells, and after surface contact with MV envelope proteins,
      SLAM is downregulated from the cell surface of activated PBL and cell lines.
      Although anti-SLAM and/or anti-CD46 antibodies block virus binding, they do not
      interfere with the contact-mediated proliferation inhibition. In addition, the
      cell-type-specific expression of SLAM does not correlate with the sensitivity of
      cells for proliferation inhibition. The data indicate that proliferation
      inhibition induced by MV contact is independent of the presence or absence of the
      virus-binding receptors SLAM and CD46.

PMID- 11312321
TI  - "Rule of six": how does the Sendai virus RNA polymerase keep count?
AB  - The "rule of six" stipulates that the Paramyxovirus RNA polymerase efficiently
      replicates only viral genomes counting 6n + 0 nucleotides. Because the
      nucleocapsid proteins (N) interact with 6 nucleotides, an exact nucleotide-N
      match at the RNA 3'-OH end (3'-OH congruence) may be required for recognition of
      an active replication promoter. Alternatively, assuming that the six positions
      for the interaction of N with the nucleotides are not equivalent, the nucleotide
      position relative to N may be critical (N phase context). The replication
      abilities of various minireplicons, designed so that the 3'-OH congruence could
      be discriminated from the N phase context, were studied. The results strongly
      suggest that the application of the rule of six depends on the recognition of
      nucleotides positioned in the proper N phase context.

PMID- 11312322
TI  - Identification and characterization of the helix-destabilizing activity of
      rotavirus nonstructural protein NSP2.
AB  - The rotavirus nonstructural protein NSP2 self-assembles into homomultimers, binds
      single-stranded RNA nonspecifically, possesses a Mg2+-dependent nucleoside
      triphosphatase (NTPase) activity, and is a component of replication
      intermediates. Because these properties are characteristics of known viral
      helicases, we examined the possibility that this was also an activity of NSP2 by
      using a strand displacement assay and purified bacterially expressed protein. The
      results revealed that, under saturating concentrations, NSP2 disrupted both DNA
      RNA and RNA-RNA duplexes; hence, the protein possesses helix-destabilizing
      activity. However, unlike typical helicases, NSP2 required neither a divalent
      cation nor a nucleotide energy source for helix destabilization. Further
      characterization showed that NSP2 displayed no polarity in destabilizing a
      partial duplex. In addition, helix destabilization by NSP2 was found to proceed
      cooperatively and rapidly. The presence of Mg2+ and other divalent cations
      inhibited by approximately one-half the activity of NSP2, probably due to the
      increased stability of the duplex substrate brought on by the cations. In
      contrast, under conditions where NSP2 functions as an NTPase, its helix
      destabilizing activity was less sensitive to the presence of Mg2+, suggesting
      that in the cellular environment the two activities associated with the protein,
      helix destabilization and NTPase, may function together. Although distinct from
      typical helicases, the helix-destabilizing activity of NSP2 is quite similar to
      that of the sigmaNS protein of reovirus and to the single-stranded DNA-binding
      proteins (SSBs) involved in double-stranded DNA replication. The presence of SSB
      like nonstructural proteins in two members of the family Reoviridae suggests a
      common mechanism of unwinding viral mRNA prior to packaging and subsequent minus
      strand RNA synthesis.

PMID- 11312323
TI  - Binding of recombinant feline immunodeficiency virus surface glycoprotein to
      feline cells: role of CXCR4, cell-surface heparans, and an unidentified non-CXCR4
      receptor.
AB  - To address the role of CXCR4 in the cell-surface attachment of the feline
      immunodeficency virus (FIV), a soluble fusion protein, gp95-Fc, consisting of the
      surface glycoprotein (SU, gp95) of either a primary (PPR) or cell line-adapted
      (34TF10) FIV strain was fused in frame with the Fc domain of human immunoglobulin
      G1. The recombinant SU-immunoadhesins were used as probes to investigate the
      cellular binding of FIV SU. In agreement with the host cell range properties of
      both viruses, binding of 34TF10 gp95-Fc was observed for all cell lines tested,
      whereas PPR gp95-Fc bound only to primary feline T cells. 34TF10 gp95-Fc also
      bound to Jurkat and HeLa cells, consistent with the ability of FIV to use human
      CXCR4 as a fusion receptor. As expected, 34TF10 gp95-Fc binding to Jurkat cells
      was blocked by addition of stromal cell-derived factor 1alpha (SDF-1alpha), as
      was binding to the 3201 feline lymphoma cell line. However, SDF-1alpha, RANTES,
      macrophage inflammatory protein 1beta, and heparin all failed to inhibit the
      binding of either gp95-Fc to primary T cells, suggesting that a non-CXCR4
      receptor is involved in the binding of FIV SU. In this regard, an unidentified 40
      kDa protein species from the surface of primary T cells but not Jurkat and 3201
      cells specifically coprecipitated with both gp95-Fc. Yet another type of binding
      of 34TF10 gp95-Fc to adherent kidney cells was noted. SDF-1alpha failed to block
      the binding of 34TF10 gp95-Fc to either HeLa, Crandel feline leukemia, or G355-5
      cells. However, binding was severely impaired in the presence of soluble heparin,
      as well as after enzymatic removal of surface heparans or on cells deficient in
      heparan expression. These overall findings suggest that in addition to CXCR4, a
      non-CXCR4 receptor and cell-surface heparans also play an important role in FIV
      gp95 cell surface interactions on specific target cells.

PMID- 11312324
TI  - Variation in adenovirus transgene expression between BALB/c and C57BL/6 mice is
      associated with differences in interleukin-12 and gamma interferon production and
      NK cell activation.
AB  - The innate immune response against replication-defective adenoviruses (Ad) is
      poorly defined. We and others have previously observed striking differences in
      the rate at which the Ad vector itself or the virus encoding a variety of
      transgenes is eliminated in different mouse strains. Here, we report that Ad
      infection of BALB/ mice is associated with sixfold-higher levels of serum alanine
      aminotransferase and that Ad transgenes induce two- to threefold-higher levels of
      intrahepatic NK cells and NK activity compared to C57BL/6 mice. The increase in
      NK activation in BALB/c mice was associated with approximately 4-fold higher
      level of mRNA expression of a newly described NKG2 receptor activator, H-60, as
      well as increased expression of interleukin-12 and gamma interferon mRNAs in
      BALB/c mice compared to C57BL/6 mice. NK depletion in BALB/c mice or defective NK
      function in C3H beige mice extended transgene expression compared to their
      appropriate controls, and attenuation of NK together with CD8 T-cell function had
      a synergistic effect. These findings indicate that there are intrinsic
      differences in the innate immune responses of different mouse strains to Ad and
      Ad transgenes and that NK cells, in cooperation with CD8 T cells, play a pivotal
      role in the early extinction of transgene expression in BALB/c mice.

PMID- 11312325
TI  - Detection and characterization of porcine endogenous retrovirus in porcine plasma
      and porcine factor VIII.
AB  - The pig genome contains porcine endogenous retroviruses (PERVs) capable of
      infecting human cells. Detection of infectious retrovirus in porcine peripheral
      blood mononuclear cells and endothelial cells suggested to us that pig plasma is
      likely to contain PERV. Both PERV env sequences and viral reverse transcriptase
      (RT) activity were detected in all plasma samples isolated from four NIH
      minipigs. To detect infectious virus from plasma, we performed a culture assay
      using three cell lines of feline, swine, and human origin that had previously
      been shown to be permissive for PERV. Infectious virus was successfully cultured
      from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR
      with env-specific primers, we could detect expression of PERV class C envelope in
      the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We
      next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found
      evidence of PERV particles, since all six lots examined were positive for PERV
      RNA and RT activity. However, infectious virus could not be detected in clinical
      lots of Hyate:C, suggesting that the manufacturing process might reduce the load
      of infectious virus to levels below detectable limits of the assay. Detection of
      infectious virus in porcine plasma confirms and extends the previous findings
      that certain porcine cells express PERV when manipulated in vitro and clearly
      demonstrates that there are porcine cells that express infectious PERV
      constitutively in vivo.

PMID- 11312326
TI  - Identification of a novel posttranscriptional regulatory element by using a rev-
      and RRE-mutated human immunodeficiency virus type 1 DNA proviral clone as a
      molecular trap.
AB  - Human immunodeficiency virus (HIV) and all other lentiviruses utilize the
      essential viral protein Rev, which binds to RRE RNA, to export their unspliced
      and partially spliced mRNAs from the nucleus. We used a rev- and RRE-defective
      HIV type 1 (HIV-1) molecular clone in complementation experiments to establish a
      method for the rapid isolation of posttranscriptional regulatory elements from
      the mammalian genome by selecting for rescue of virus replication. Viruses
      rescued by this method contained a novel element with homology to rodent
      intracisternal A-particle (IAP) retroelements. A functional element was contained
      within a 247-nucleotide fragment named RNA transport element (RTE), which was
      able to promote replication of the Rev- and RRE-defective HIV-1 in both human
      lymphoid cell lines and primary lymphocytes, demonstrating its potent
      posttranscriptional function. RTE was functional in many cell types, indicating
      that the cellular factors that recognize RTE are widely expressed and
      evolutionarily conserved. RTE also promoted RNA export from Xenopus oocyte
      nuclei. RTE-mediated RNA transport was CRM1 independent, and RTE did not show
      high affinity for binding to mRNA export factor TAP/NXF1. Since CRM1 and TAP/NXF1
      are critical export receptors associated with the two recognized mRNA export
      pathways, these results suggest that RTE functions via a distinct export
      mechanism. Taken together, our results identify a novel posttranscriptional
      control element that uses a conserved cellular export mechanism.

PMID- 11312327
TI  - Equine infectious anemia virus genomic evolution in progressor and nonprogressor
      ponies.
AB  - A primary mechanism of lentivirus persistence is the ability of these viruses to
      evolve in response to biological and immunological selective pressures with a
      remarkable array of genetic and antigenic variations that constitute a perpetual
      natural experiment in genetic engineering. A widely accepted paradigm of
      lentivirus evolution is that the rate of genetic variation is correlated directly
      with the levels of virus replication: the greater the viral replication, the more
      opportunities that exist for genetic modifications and selection of viral
      variants. To test this hypothesis directly, we examined the patterns of equine
      infectious anemia virus (EIAV) envelope variation during a 2.5-year period in
      experimentally infected ponies that differed markedly in clinical progression and
      in steady-state levels of viral replication as indicated by plasma virus genomic
      RNA assays. The results of these comprehensive studies revealed for the first
      time similar extents of envelope gp90 variation in persistently infected ponies
      regardless of the number of disease cycles (one to six) and viremia during
      chronic disease. The extent of envelope variation was also independent of the
      apparent steady-state levels of virus replication during long-term asymptomatic
      infection, varying from undetectable to 10(5) genomic RNA copies per ml of
      plasma. In addition, the data confirmed the evolution of distinct virus
      populations (genomic quasispecies) associated with sequential febrile episodes
      during acute and chronic EIA and demonstrated for the first time ongoing envelope
      variation during long-term asymptomatic infections. Finally, comparison of the
      rates of evolution of the previously defined EIAV gp90 variable domains
      demonstrated distinct differences in the rates of nucleotide and amino acid
      sequence variation, presumably reflecting differences in the ability of different
      envelope domains to respond to immune or other biological selection pressures.
      Thus, these data suggest that EIAV variation can be associated predominantly with
      ongoing low levels of virus replication and selection in target tissues, even in
      the absence of substantial levels of plasma viremia, and that envelope variation
      continues during all stages of persistent infection as the virus successfully
      avoids clearance by host defense mechanisms.

PMID- 11312328
TI  - During readaptation in vivo, a tissue culture-adapted strain of feline
      immunodeficiency virus reverts to broad neutralization resistance at different
      times in individual hosts but through changes at the same position of the surface
      glycoprotein.
AB  - The broad resistance to antibody-mediated neutralization of lentiviruses recently
      isolated from infected hosts is a poorly understood feature which might
      contribute to the ability of these viruses to persist and to the failure of
      experimental vaccines to protect against virulent viruses. We studied the
      underlying molecular mechanisms by examining the evolution of a neutralization
      sensitive, tissue culture-adapted strain of feline immunodeficiency virus upon
      reinoculation into specific-pathogen-free cats. Reversion to broad neutralization
      resistance was observed in seven of seven inoculated animals and, in individual
      hosts, started to develop between less than 4 and more than 15 months from
      infection. After comparison of the envelope sequences of the inoculum virus, of
      an additional 4 neutralization-sensitive in vitro variants, and of 14 ex vivo
      derived variants (6 neutralization sensitive, 5 resistant, and 3 with
      intermediate phenotype), a Lys-->Asn or -->Glu change at position 481 in the V4
      region of the surface glycoprotein appeared as a key player in the reversion.
      This conclusion was confirmed by mutagenesis of molecularly cloned virus.
      Analysis of viral quasispecies and biological clones showed that the intermediate
      phenotype was due to transient coexistence of neutralization-sensitive and 
      resistant variants. Since the amino acid position involved was the same in four
      of four recent revertants, it is suggested that the number of residues that
      control reversion to broad neutralization resistance in FIV might be very
      limited. Amino acid 481 was found to be changed only in one of three putative
      long-term revertants. These variants shared a Ser-->Asn change at position 557 in
      region V5, which probably collaborated with other mutations in long-term
      maintenance of neutralization resistance, as suggested by the study of
      mutagenized virus.

PMID- 11312329
TI  - Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the
      respiratory syncytial virus (RSV) G and F proteins can be used to achieve
      simultaneous mucosal immunization against RSV and HPIV3.
AB  - Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant
      bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3
      counterparts, was used to express the major protective antigens of respiratory
      syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV
      and HPIV3. The attenuation of rB/HPIV3 is provided by the host range restriction
      of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were
      placed under the control of PIV3 transcription signals and inserted individually
      into the rB/HPIV3 genome in the promoter-proximal position preceding the
      nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF
      (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus
      expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its
      rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of
      hamsters, and each induced RSV serum antibody titers similar to those induced by
      RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection.
      Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both
      viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28
      days later. These results describe a vaccine strategy that obviates the technical
      challenges associated with a live attenuated RSV vaccine, providing, against the
      two leading viral agents of pediatric respiratory tract disease, a bivalent
      vaccine whose attenuation phenotype is based on the extensive host range sequence
      differences of BPIV3.

PMID- 11312330
TI  - Receptor specificities of human respiroviruses.
AB  - Through their hemagglutinin-neuraminidase glycoprotein, parainfluenza viruses
      bind to sialic acid-containing glycoconjugates to initiate infection. Although
      the virus-receptor interaction is a key factor of infection, the exact nature of
      the receptors that human parainfluenza viruses recognize has not been determined.
      We evaluated the abilities of human parainfluenza virus types 1 (hPIV-1) and 3
      (hPIV-3) to bind to different types of gangliosides. Both hPIV-1 and hPIV-3
      preferentially bound to neolacto-series gangliosides containing a terminal N
      acetylneuraminic acid (NeuAc) linked to N-acetyllactosamine (Galbeta1-4GlcNAc) by
      the alpha2-3 linkage (NeuAcalpha2-3Galbeta1-4GlcNAc). Unlike hPIV-1, hPIV-3 bound
      to gangliosides with a terminal NeuAc linked to Galbeta1-4GlcNAc through an
      alpha2-6 linkage (NeuAcalpha2-6Galbeta1-4GlcNAc) or to gangliosides with a
      different sialic acid, N-glycolylneuraminic acid (NeuGc), linked to Galbeta1
      4GlcNAc (NeuGcalpha2-3Galbeta1-4GlcNAc). These results indicate that the
      molecular species of glycoconjugate that hPIV-1 recognizes are more limited than
      those recognized by hPIV-3. Further analysis using purified gangliosides revealed
      that the oligosaccharide core structure is also an important element for binding.
      Gangliosides that contain branched N-acetyllactosaminoglycans in their core
      structure showed higher avidity than those without them. Agglutination of human,
      cow, and guinea pig erythrocytes but not equine erythrocytes by hPIV-1 and hPIV-3
      correlated well with the presence or the absence of sialic acid-linked branched N
      acetyllactosaminoglycans on the cell surface. Finally, NeuAcalpha2-3I, which
      bound to both viruses, inhibited virus infection of Lewis lung carcinoma-monkey
      kidney cells in a dose-dependent manner. We conclude that hPIV-1 and hPIV-3
      preferentially recognize oligosaccharides containing branched N
      acetyllactosaminoglycans with terminal NeuAcalpha2-3Gal as receptors and that
      hPIV-3 also recognizes NeuAcalpha2-6Gal- or NeuGcalpha2-3Gal-containing
      receptors. These findings provide important information that can be used to
      develop inhibitors that prevent human parainfluenza virus infection.

PMID- 11312331
TI  - Enhancement of hepatitis C virus RNA replication by cell culture-adaptive
      mutations.
AB  - Studies of the Hepatitis C virus (HCV) replication cycle have been made possible
      with the development of subgenomic selectable RNAs that replicate autonomously in
      cultured cells. In these replicons the region encoding the HCV structural
      proteins was replaced by the neomycin phosphotransferase gene, allowing the
      selection of transfected cells that support high-level replication of these RNAs.
      Subsequent analyses revealed that, within selected cells, HCV RNAs had acquired
      adaptive mutations that increased the efficiency of colony formation by an
      unknown mechanism. Using a panel of replicons that differed in their degrees of
      cell culture adaptation, in this study we show that adaptive mutations enhance
      RNA replication. Transient-transfection assays that did not require selection of
      transfected cells demonstrated a clear correlation between the level of
      adaptation and RNA replication. The highest replication level was found with an
      adapted replicon carrying two amino acid substitutions located in NS3 and one in
      NS5A that acted synergistically. In contrast, the nonadapted RNA replicated only
      transiently and at a low level. The correlation between the efficiency of colony
      formation and RNA replication was corroborated with replicons in which the
      selectable marker gene was replaced by the gene encoding firefly luciferase. Upon
      transfection of naive Huh-7 cells, the levels of luciferase activity directly
      reflected the replication efficiencies of the various replicon RNAs. These
      results show that cell culture-adaptive mutations enhance HCV RNA replication.

PMID- 11312332
TI  - M-X-I motif of semliki forest virus capsid protein affects nucleocapsid assembly.
AB  - Alphavirus budding is driven by interactions between spike and nucleocapsid
      proteins at the plasma membrane. The binding motif, Y-X-L, on the spike protein
      E2 and the corresponding hydrophobic cavity on the capsid protein were described
      earlier. The spike-binding cavity has also been suggested to bind an internal
      hydrophobic motif, M113-X-I115, of the capsid protein. In this study we found
      that replacement of amino acids M113 and I115 with alanines, as single or double
      mutations, abolished formation of intracellular nucleocapsids. The mutants could
      still bud efficiently, but the NCs in the released virions were not stable after
      removal of the membrane and spike protein layer. In addition to wild-type
      spherical particles, elongated multicored particles were found at the plasma
      membrane and released from the host cell. We conclude that the internal capsid
      motif has a biological function in the viral life cycle, especially in assembly
      of nucleocapsids. We also provide further evidence that alphaviruses may assemble
      and bud from the plasma membrane in the absence of preformed nucleocapsids.

PMID- 11312333
TI  - Coupling between replication and packaging of flavivirus RNA: evidence derived
      from the use of DNA-based full-length cDNA clones of Kunjin virus.
AB  - In order to study whether flavivirus RNA packaging is dependent on RNA
      replication, we generated two DNA-based Kunjin virus constructs, pKUN1 and
      pKUN1dGDD, allowing continuous production of replicating (wild-type) and
      nonreplicating (with a deletion of the NS5 gene RNA-polymerase motif GDD) full
      length Kunjin virus RNAs, respectively, via nuclear transcription by cellular RNA
      polymerase II. As expected, transfection of pKUN1 plasmid DNA into BHK cells
      resulted in the recovery of secreted infectious Kunjin virions. Transfection of
      pKUN1dGDD DNA into BHK cells, however, did not result in the recovery of any
      secreted virus particles containing encapsidated dGDD RNA, despite an apparent
      accumulation of this RNA in cells demonstrated by Northern blot analysis and its
      efficient translation demonstrated by detection of correctly processed labeled
      structural proteins (at least prM and E) both in cells and in the culture fluid
      using coimmunoprecipitation analysis with anti-E antibodies. In contrast, when
      dGDD RNA was produced even in much smaller amounts in pKUN1dGDD DNA-transfected
      repBHK cells (where it was replicated via complementation), it was packaged into
      secreted virus particles. Thus, packaging of defective Kunjin virus RNA could
      occur only when it was replicated. Our results with genome-length Kunjin virus
      RNA and the results with poliovirus replicon RNA (C. I. Nugent et al., J. Virol.
      73:427-435, 1999), both demonstrating the necessity for the RNA to be replicated
      before it can be packaged, strongly suggest the existence of a common mechanism
      for minimizing amplification and transmission of defective RNAs among the
      quasispecies in positive-strand RNA viruses. This mechanism may thus help
      alleviate the high-copy error rate of RNA-dependent RNA polymerases.

PMID- 11312334
TI  - Locus control region of the human CD2 gene in a lentivirus vector confers
      position-independent transgene expression.
AB  - Vectors derived from murine leukemia virus (MLV) have been used in many human
      gene therapy clinical trials. However, insertion of the locus control regions
      (LCRs) derived from the beta-globin gene locus or the CD2 gene into MLV vectors
      frequently led to vector rearrangement. Since the human immunodeficiency virus
      (HIV) sequence diverges significantly from the MLV sequence, we tested whether
      the LCR sequence is more stable in the context of an HIV vector. Clones derived
      from human fibrosarcoma line HT1080 cells transduced with an HIV vector
      containing the T-cell-specific CD2 LCR exhibit the same wide range of transgene
      expression as clones lacking the LCR. In contrast, Jurkat and primary T-cell
      clones derived from the transduction of the LCR-containing vector show, on
      average, a three- to fourfold increase in transgene expression relative to that
      of the control vector. This is consistent with previous observations that the CD2
      LCR contains a T-cell-specific enhancer. In addition, the clones derived from the
      LCR-containing vector have a much lower clonal variation in transgene expression
      than those derived from the control vector. We also demonstrate that the level of
      transgene expression is proportional to the vector copy number. These results
      suggest that the human CD2 LCR sequence is compatible with HIV vector sequences
      and confers enhanced integration site-independent and copy number-dependent
      expression of the transgene. Thus, HIV vectors may represent the ideal vehicle to
      deliver genes controlled by various cis-acting elements such as LCRs.

PMID- 11312335
TI  - Passive transfer of antibodies protects immunocompetent and imunodeficient mice
      against lethal Ebola virus infection without complete inhibition of viral
      replication.
AB  - Ebola hemorrhagic fever is a severe, usually fatal illness caused by Ebola virus,
      a member of the filovirus family. The use of nonhomologous immune serum in animal
      studies and blood from survivors in two anecdotal reports of Ebola hemorrhagic
      fever in humans has shown promise, but the efficacy of these treatments has not
      been demonstrated definitively. We have evaluated the protective efficacy of
      polyclonal immune serum in a mouse model of Ebola virus infection. Our results
      demonstrate that mice infected subcutaneously with live Ebola virus survive
      infection and generate high levels of anti-Ebola virus immunoglobulin G (IgG).
      Passive transfer of immune serum from these mice before challenge protected upto
      100% of naive mice against lethal Ebola virus infection. Protection correlated
      with the level of anti-Ebola virus IgG titers, and passive treatment with high
      titer antiserum was associated with a delay in the peak of viral replication.
      Transfer of immune serum to SCID mice resulted in 100% survival after lethal
      challenge with Ebola virus, indicating that antibodies alone can protect from
      lethal disease. Thus antibodies suppress or delay viral growth, provide
      protection against lethal Ebola virus infection, and may not require
      participation of other immune components for protection.

PMID- 11312337
TI  - DC-SIGN interactions with human immunodeficiency virus type 1 and 2 and simian
      immunodeficiency virus.
AB  - Dendritic cells (DCs) efficiently bind and transmit human immunodeficiency virus
      (HIV) to cocultured T cells and so may play an important role in HIV
      transmission. DC-SIGN, a novel C-type lectin that is expressed in DCs, has
      recently been shown to bind R5 HIV type 1 (HIV-1) strains and a laboratory
      adapted X4 strain. To characterize the interaction of DC-SIGN with primate
      lentiviruses, we investigated the structural determinants of DC-SIGN required for
      virus binding and transmission to permissive cells. We constructed a panel of DC
      SIGN mutants and established conditions which allowed comparable cell surface
      expression of all mutants. We found that R5, X4, and R5X4 HIV-1 isolates as well
      as simian immunodeficiency and HIV-2 strains bound to DC-SIGN and could be
      transmitted to CD4/coreceptor-positive cell types. DC-SIGN contains a single N
      linked carbohydrate chain that is important for efficient cell surface expression
      but is not required for DC-SIGN-mediated virus binding and transmission. In
      contrast, C-terminal deletions removing either the lectin binding domain or the
      repeat region abrogated DC-SIGN function. Trypsin-EDTA treatment inhibited DC
      SIGN mediated infection, indicating that virus was maintained at the surface of
      the DC-SIGN-expressing cells used in this study. Finally, quantitative
      fluorescence-activated cell sorting analysis of AU1-tagged DC-SIGN revealed that
      the efficiency of virus transmission was strongly affected by variations in DC
      SIGN expression levels. Thus, variations in DC-SIGN expression levels on DCs
      could greatly affect the susceptibility of human individuals to HIV infection.

PMID- 11312336
TI  - Regulation of human immunodeficiency virus type 1 replication in human T
      lymphocytes by nitric oxide.
AB  - Addition of nitric oxide (NO) donors to mitogen-activated human immunodeficiency
      virus type 1 (HIV-1)-infected peripheral blood mononuclear cultures produced a
      significant increase in virus replication, and this effect was not associated
      with a change in cell proliferation. This effect was only observed with T-tropic
      X4 or X4R5 virus but not with R5 virus. Moreover, HIV-1 replication in mitogen
      stimulated cultures was partially prevented by the specific inhibitors of the
      inducible nitric oxide synthase (iNOS). NO donors also enhanced HIV-1 infection
      of the human T-cell lines, Jurkat and MT-2. We have also observed that NO leads
      to an enhancement of HIV-1 replication in resting human T cells transfected with
      a plasmid carrying the entire HIV-1 genome and activated with phorbol ester plus
      ionomycin. Thus, in those cultures NO donors strongly potentiated HIV-1
      replication in a dose-dependent manner, up to levels comparable to those with
      tumor necrosis factor alpha (TNF-alpha) stimulation. Furthermore, iNOS inhibitors
      decreased HIV-1 replication in HIV-1-transfected T cells to levels similar to
      those obtained with neutralizing anti-TNF-alpha antibodies. Moreover, HIV-1
      replication induced iNOS and TNF-alpha transcription in T cells and T-cell lines.
      Interestingly, NO donors also stimulated long terminal repeat (LTR)-driven
      transcription whereas iNOS inhibitors partially blocked TNF-alpha-induced LTR
      transcription. Therefore, our results suggest that NO is involved in HIV-1
      replication, especially that induced by TNF-alpha.

PMID- 11312338
TI  - Efficient conversion of normal prion protein (PrP) by abnormal hamster PrP is
      determined by homology at amino acid residue 155.
AB  - In the transmissible spongiform encephalopathies, disease is closely associated
      with the conversion of the normal proteinase K-sensitive host prion protein (PrP
      sen) to the abnormal proteinase K-resistant form (PrP-res). Amino acid sequence
      homology between PrP-res and PrP-sen is important in the formation of new PrP-res
      and thus in the efficient transmission of infectivity across species barriers. It
      was previously shown that the generation of mouse PrP-res was strongly influenced
      by homology between PrP-sen and PrP-res at amino acid residue 138, a residue
      located in a region of loop structure common to PrP molecules from many different
      species. In order to determine if homology at residue 138 also affected the
      formation of PrP-res in a different animal species, we assayed the ability of
      hamster PrP-res to convert a panel of recombinant PrP-sen molecules to protease
      resistant PrP in a cell-free conversion system. Homology at amino acid residue
      138 was not critical for the formation of protease-resistant hamster PrP. Rather,
      homology between PrP-sen and hamster PrP-res at amino acid residue 155 determined
      the efficiency of formation of a protease-resistant product induced by hamster
      PrP-res. Structurally, residue 155 resides in a turn at the end of the first
      alpha helix in hamster PrP-sen; this feature is not present in mouse PrP-sen.
      Thus, our data suggest that PrP-res molecules isolated from scrapie-infected
      brains of different animal species have different PrP-sen structural requirements
      for the efficient formation of protease-resistant PrP.

PMID- 11312339
TI  - Transport of human immunodeficiency virus type 1 pseudoviruses across the blood
      brain barrier: role of envelope proteins and adsorptive endocytosis.
AB  - Blood-borne human immunodeficiency virus type 1 (HIV-1) crosses the blood-brain
      barrier (BBB) to induce brain dysfunction. How HIV-1 crosses the BBB is unclear.
      Most work has focused on the ability of infected immune cells to cross the BBB,
      with less attention devoted to the study of free virus. Since the HIV-1 coat
      glycoprotein gp120 can cross the BBB, we postulated that gp120 might be key in
      determining whether free virus can cross the BBB. We used radioactive virions
      which do (Env+) or do not (Env-) bear the envelope proteins to characterize the
      ability of HIV-1 to be taken up by the murine BBB. In vivo and in vitro studies
      showed that the envelope proteins are key to the uptake of free virus and that
      uptake was enhanced by wheat germ agglutinin, strongly suggesting that the
      envelope proteins induce viral adsorptive endocytosis and transcytosis in brain
      endothelia. Capillary depletion showed that Env+ virus completely crossed the
      vascular BBB to enter the parenchyma of the brain. Virus also entered the
      cerebrospinal fluid, suggesting passage across the choroid plexus as well. About
      0.22% of the intravenously injected dose was taken up per g of brain. In vitro
      studies showed that postinternalization membrane cohesion (membrane binding not
      reversed with acid wash or cell lysis) was a regulated event. Intact virus was
      recovered from the brain endothelial cytosol and was effluxed from the
      endothelial cells. These results show that free HIV-1 can cross the BBB by an
      event related to adsorptive endocytosis and mediated by the envelope proteins.

PMID- 11312340
TI  - Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced
      apoptosis and interferon synthesis.
AB  - Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is
      an economically important cattle pathogen with a worldwide distribution. Both
      noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be isolated from
      persistently infected cattle suffering from the lethal mucosal disease. The cp
      biotype correlates with the production of the NS3 nonstructural protein, which in
      the corresponding ncp biotype is present in its uncleaved form, NS23. Previously,
      we have shown that cp but not ncp BVDV induces the formation of alpha/beta
      interferons in bovine macrophages. In this study, we demonstrate that ncp BVDV
      inhibits the induction of apoptosis and the expression of interferon alpha/beta
      by poly(IC), a synthetic double-stranded RNA (dsRNA). Inhibition was observed
      only in cells which had been infected with ncp BVDV at least 12 h prior to the
      addition of dsRNA, which indicates that expression of viral proteins is necessary
      for the ncp virus to inhibit the effects of poly(IC). Additional experiments
      using transfected poly(IC) showed that ncp BVDV interfered with the intracellular
      action of dsRNA rather than with its uptake into the cells. Infected cells were
      not resistant to induction of apoptosis by actinomycin D or staurosporine, which
      suggests that ncp BVDV may specifically interfere with signaling through dsRNA.
      Interference with the innate antiviral host responses may explain the successful
      establishment of persistent infection by ncp BVDV in fetuses early in their
      development.

PMID- 11312341
TI  - Selective induction of apoptosis in antigen-presenting cells in mice by
      Parapoxvirus ovis.
AB  - Viruses have evolved numerous mechanisms to avoid host immune reactions. Here we
      report a mechanism by which Parapoxvirus ovis (PPVO) interferes with antigen
      presentation. PPVO (orf virus) causes orf, an acute skin disease of sheep and
      goats worldwide. Importantly, PPVO can repeatedly infect its host in spite of a
      vigorous inflammatory and host immune response to the infection. We demonstrate
      in a mouse system that PPVO induces apoptosis in a significant number of antigen
      presenting cells after intraperitoneal injection using the CD95 pathway, thus
      preventing a primary T-cell response. We also show that PPVO induces a
      compensatory activation of the immune system. Our results may help to explain the
      phenomenon that natural PPVO infections in sheep occur repeatedly even after
      short intervals. They also suggest that the combination of immunosuppressive and
      immunostimulatory mechanisms is an effective survival strategy that might be used
      in other viruses as well.

PMID- 11312342
TI  - Induction of pRb degradation by the human papillomavirus type 16 E7 protein is
      essential to efficiently overcome p16INK4a-imposed G1 cell cycle Arrest.
AB  - It has previously been shown that the E7 protein from the cutaneous human
      papillomavirus type 1 (HPV1), which is associated with benign skin lesions, binds
      the product of the tumor suppressor gene retinoblastoma (pRb) with an efficiency
      similar to that of the E7 protein from the oncogenic HPV type 16. Despite this
      ability, HPV1 E7 does not display any activity in transforming primary cells. In
      addition, the two viral proteins differ in their mechanisms of targeting pRb.
      HPV16 E7 promotes pRb destabilization, while cells expressing HPV1 E7 do not show
      any decrease in pRb levels. In this study, we show that HPV1 E7, in contrast to
      HPV16 E7, has only a weak activity to neutralize the effect of cyclin-dependent
      kinase inhibitor p16INK4a. By generation of HPV1/16 E7 chimeric proteins, we have
      identified a central motif in the two E7 proteins, which determines their
      different abilities to overcome the p16INK4a-mediated cell cycle arrest. This
      motif is located downstream of the pRb-binding domain and comprises only three
      amino acids in HPV16 E7. Swapping this central motif in the two viral proteins
      causes an exchange of their activities involved in circumventing the inhibitory
      function of p16INK4a. Most importantly, our data show that the efficiency of the
      E7 proteins in neutralizing the inhibitory effect of p16INK4a correlates with
      their ability to promote pRb degradation.

PMID- 11312343
TI  - In vivo T-lymphocyte activation and transient reduction of viral replication in
      macaques infected with simian immunodeficiency virus.
AB  - While it is well established that cellular activation can increase human
      immunodeficiency virus (HIV) replication in T lymphocytes, it is also clear that
      both activated CD8+ and CD4+ T lymphocytes mediate anti-HIV activity. To assess
      the relative importance of these contrary effects on HIV replication in vivo, we
      evaluated the consequences of Mycobacterium bovis BCG and staphylococcal
      enterotoxin B (SEB) inoculation in vivo in rhesus monkeys chronically infected
      with simian immunodeficiency virus of macaques (SIVmac). BCG inoculation induced
      as much as a 2.5-log reduction of plasma and intracellular SIV RNA in SIVmac
      infected monkeys. This down-regulation of virus replication persisted as long as
      4 weeks after BCG inoculation. Similarly, SEB injection resulted in up to a 3-log
      decrease in plasma and intracellular SIV RNA in SIVmac-infected macaques.
      Interestingly, the short-term reduction of viremia in these monkeys correlated
      with the peak in vivo production of SEB- and BCG-induced cytokine responses.
      However, no long-term clinical benefit was observed in the SIVmac-infected
      macaques. These studies provide in vivo evidence that potent T-cell stimulation
      driven by antigens other than the virus itself can, under some circumstances,
      mediate short-term reduction of viremia in AIDS virus-infected individuals.

PMID- 11312344
TI  - Structural consequences of cyclophilin A binding on maturational refolding in
      human immunodeficiency virus type 1 capsid protein.
AB  - While several cellular proteins are incorporated in the human immunodeficiency
      virus type 1 virion, cyclophilin (CyP) A is the only one whose absence has been
      demonstrated to impair infectivity. Incorporation of the cytosolic protein
      results from interaction with a highly exposed Pro-rich loop in the N-terminal
      region of the capsid (CA) domain of the precursor polyprotein, Pr55(Gag). Even
      when prevented from interacting with CyP A, Pr55Gag still forms particles that
      proceed to mature into morphologically wild-type virions, suggesting that CyP A
      influences a postassembly event. The nature of this CyP A influence has yet to be
      elucidated. Here, we show that while CyP A binds both Gag and mature CA proteins,
      the two binding interactions are actually different. Tryptophan 121 (W121) in CyP
      A distinguished the two proteins: a phenylalanine substitution (W121F) impaired
      binding of mature CA protein but not of Gag. This indicates the occurrence of a
      maturation-dependent switch in the conformation of the Pro-rich loop. A
      structural consequence of Gag binding to CyP A was to block this maturational
      refolding, resulting in a 24-kDa CA protein retaining the immature Pro-rich loop
      conformation. Using trypsin as a structure probe, we demonstrate that the
      conformation of the C-terminal region in mature CA is also a product of
      maturational refolding. Binding to wild-type CyP A altered this conformation, as
      indicated by a reduction in the accessibility of Cys residue(s) in the region to
      chemical modification. Hence, the end result of binding to CyP A, whether the Pro
      rich loop is in the context of Gag or mature CA protein, is a structurally
      modified mature CA protein. The postassembly role of CyP A may be mediated
      through these modified mature CA proteins.

PMID- 11312345
TI  - Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell
      cell spread of herpes simplex virus type 1.
AB  - We recently found a novel cell-cell adhesion system at cadherin-based adherens
      junctions (AJs), consisting at least of nectin, a Ca(2+)-independent homophilic
      immunoglobulin-like adhesion molecule, and afadin, an actin filament-binding
      protein that connects nectin to the actin cytoskeleton. Nectin is associated with
      cadherin through afadin and alpha-catenin. The cadherin-catenin system increases
      the concentration of nectin at AJs in an afadin-dependent manner. Nectin
      constitutes a family consisting of three members: nectin-1, -2, and -3. Nectin-1
      serves as an entry and cell-cell spread mediator of herpes simplex virus type 1
      (HSV-1). We studied here a role of the interaction of nectin-1alpha with afadin
      in entry and/or cell-cell spread of HSV-1. By the use of cadherin-deficient L
      cells overexpressing the full length of nectin-1alpha capable of interacting with
      afadin and L cells overexpressing a truncated form of nectin-1alpha incapable of
      interacting with afadin, we found that the interaction of nectin-1alpha with
      afadin increased the efficiency of cell-cell spread, but not entry, of HSV-1.
      This interaction did not affect the binding to nectin-1alpha of glycoprotein D, a
      viral component mediating entry of HSV-1 into host cells. Furthermore, the
      cadherin-catenin system increased the efficiency of cell-cell spread of HSV-1,
      although it also increased the efficiency of entry of HSV-1. It is likely that
      efficient cell-cell spread of HSV-1 is caused by afadin-dependent concentrated
      localization of nectin-1alpha at cadherin-based AJs.

PMID- 11312346
TI  - N-glycans of F protein differentially affect fusion activity of human respiratory
      syncytial virus.
AB  - The human respiratory syncytial virus (Long strain) fusion protein contains six
      potential N-glycosylation sites: N27, N70, N116, N120, N126, and N500. Site
      directed mutagenesis of these positions revealed that the mature fusion protein
      contains three N-linked oligosaccharides, attached to N27, N70, and N500. By
      introducing these mutations into the F gene in different combinations, four more
      mutants were generated. All mutants, including a triple mutant devoid of any N
      linked oligosaccharide, were efficiently transported to the plasma membrane, as
      determined by flow cytometry and cell surface biotinylation. None of the
      glycosylation mutations interfered with proteolytic activation of the fusion
      protein. Despite similar levels of cell surface expression, the glycosylation
      mutants affected fusion activity in different ways. While the N27Q mutation did
      not have an effect on syncytium formation, loss of the N70-glycan caused a fusion
      activity increase of 40%. Elimination of both N-glycans (N27/70Q mutant) reduced
      the fusion activity by about 50%. A more pronounced reduction of the fusion
      activity of about 90% was observed with the mutants N500Q, N27/500Q, and
      N70/500Q. Almost no fusion activity was detected with the triple mutant
      N27/70/500Q. These data indicate that N-glycosylation of the F2 subunit at N27
      and N70 is of minor importance for the fusion activity of the F protein. The
      single N-glycan of the F1 subunit attached to N500, however, is required for
      efficient syncytium formation.

PMID- 11312347
TI  - Human papillomavirus virus-like particles are efficient oral immunogens when
      coadministered with Escherichia coli heat-labile enterotoxin mutant R192G or CpG
      DNA.
AB  - Certain human papillomaviruses (HPVs) cause most cervical cancer, which remains a
      significant source of morbidity and mortality among women worldwide. HPV
      recombinant virus-like particles (VLPs) are promising vaccine candidates for
      controlling anogenital HPV disease and are now being evaluated as a parenteral
      vaccine modality in human subjects. Vaccines formulated for injection generally
      are more costly, more difficult to administer, and less acceptable to recipients
      than are mucosally administered vaccines. Since oral delivery represents an
      attractive alternative to parenteral injection for large-scale human vaccination,
      the oral immunogenicity of HPV type 11 (HPV-11) VLPs in mice was previously
      investigated; it was found that a modest systemic neutralizing antibody response
      was induced (R. C. Rose, C. Lane, S. Wilson, J. A. Suzich, E. Rybicki, and A. L.
      Williamson, Vaccine 17:2129-2135, 1999). Here we examine whether VLPs of other
      genotypes may also be immunogenic when administered orally and whether mucosal
      adjuvants can be used to enhance VLP oral immunogenicity. We show that HPV-16 and
      HPV-18 VLPs are immunogenic when administered orally and that oral
      coadministration of these antigens with Escherichia coli heat-labile enterotoxin
      (LT) mutant R192G (LT R192G) or CpG DNA can significantly improve anti-VLP
      humoral responses in peripheral blood and in genital mucosal secretions. Our
      results also suggest that LT R192G may be superior to CpG DNA in this ability.
      These findings support the concept of oral immunization against anogenital HPV
      disease and suggest that clinical studies involving this approach may be
      warranted.

PMID- 11312348
TI  - Importance of the N terminus of rous sarcoma virus protease for structure and
      enzymatic function.
AB  - All retrovirus proteases (PRs) are homodimers, and dimerization is essential for
      enzymatic function. The dimer is held together largely by a short four-stranded
      antiparallel beta sheet composed of the four or five N-terminal amino acid
      residues and a similar stretch of residues from the C terminus. We have found
      that the enzymatic and structural properties of Rous sarcoma virus (RSV) PR are
      exquisitely sensitive to mutations at the N terminus. Deletion of one or three
      residues, addition of one residue, or substitution of alanine for the N-terminal
      leucine reduced enzymatic activity on peptide and protein substrates 100- to
      1,000-fold. The purified mutant proteins remained monomeric up to a concentration
      of about 2 mg/ml, as determined by dynamic light scattering. At higher
      concentrations, dimerization was observed, but the dimer lacked or was deficient
      in enzymatic activity and thus was inferred to be structurally distinct from a
      wild-type dimer. The mutant protein lacking three N-terminal residues (DeltaLAM),
      a form of PR occurring naturally in virions, was examined by nuclear magnetic
      resonance spectroscopy and found to be folded at concentrations where it was
      monomeric. This result stands in contrast to the report that a similarly
      engineered monomeric PR of human immunodeficiency virus type 1 is unstructured.
      Heteronuclear single quantum coherence spectra of the mutant at concentrations
      where either monomers or dimers prevail were nearly identical. However, these
      spectra differed from that of the dimeric wild-type RSV PR. These results imply
      that the chemical environment of many of the amide protons differed and thus that
      the three-dimensional structure of the DeltaLAM PR mutant is different from that
      of the wild-type PR. The structure of this mutant protein may serve as a model
      for the structure of the PR domain of the Gag polyprotein and may thus give clues
      to the initiation of proteolytic maturation in retroviruses.

PMID- 11312349
TI  - Molecular modeling and biochemical characterization reveal the mechanism of
      hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine
      (FTC).
AB  - Success in treating hepatitis B virus (HBV) infection with nucleoside analog
      drugs like lamivudine is limited by the emergence of drug-resistant viral strains
      upon prolonged therapy. The predominant lamivudine resistance mutations in HBV
      infected patients are Met552IIe and Met552Val (Met552Ile/Val), frequently in
      association with a second mutation, Leu528Met. The effects of Leu528Met,
      Met552Ile, and Met552Val mutations on the binding of HBV polymerase inhibitors
      and the natural substrate dCTP were evaluated using an in vitro HBV polymerase
      assay. Susceptibility to lamivudine triphosphate (3TCTP), emtricitabine
      triphosphate (FTCTP), adefovir diphosphate, penciclovir triphosphate, and
      lobucavir triphosphate was assessed by determination of inhibition constants
      (K(i)). Recognition of the natural substrate, dCTP, was assessed by determination
      of Km values. The results from the in vitro studies were as follows: (i) dCTP
      substrate binding was largely unaffected by the mutations, with Km changing
      moderately, only in a range of 0.6 to 2.6-fold; (ii) K(i)s for 3TCTP and FTCTP
      against Met552Ile/Val mutant HBV polymerases were increased 8- to 30-fold; and
      (iii) the Leu528Met mutation had a modest effect on direct binding of these beta
      L-oxathiolane ring-containing nucleotide analogs. A three-dimensional homology
      model of the catalytic core of HBV polymerase was constructed via extrapolation
      from retroviral reverse transcriptase structures. Molecular modeling studies
      using the HBV polymerase homology model suggested that steric hindrance between
      the mutant amino acid side chain and lamivudine or emtricitabine could account
      for the resistance phenotype. Specifically, steric conflict between the Cgamma2
      methyl group of Ile or Val at position 552 in HBV polymerase and the sulfur atom
      in the oxathiolane ring (common to both beta-L-nucleoside analogs lamivudine and
      emtricitabine) is proposed to account for the resistance observed upon
      Met552Ile/Val mutation. The effects of the Leu528Met mutation, which also occurs
      near the HBV polymerase active site, appeared to be less direct, potentially
      involving rearrangement of the deoxynucleoside triphosphate-binding pocket
      residues. These modeling results suggest that nucleotide analogs that are beta-D
      enantiomers, that have the sulfur replaced by a smaller atom, or that have
      modified or acyclic ring systems may retain activity against lamivudine-resistant
      mutants, consistent with the observed susceptibility of these mutants to
      adefovir, lobucavir, and penciclovir in vitro and adefovir in vivo.

PMID- 11312350
TI  - Cell-to-cell contact results in a selective translocation of maternal human
      immunodeficiency virus type 1 quasispecies across a trophoblastic barrier by both
      transcytosis and infection.
AB  - Mother-to-child transmission can occur in utero, mainly intrapartum and
      postpartum in case of breastfeeding. In utero transmission is highly restricted
      and results in selection of viral variant from the mother to the child. We have
      developed an in vitro system that mimics the interaction between viruses,
      infected cells present in maternal blood, and the trophoblast, the first barrier
      protecting the fetus. Trophoblastic BeWo cells were grown as a tight polarized
      monolayer in a two-chamber system. Cell-free virions applied to the apical pole
      neither crossed the barrier nor productively infected BeWo cells. In contrast,
      apical contact with human immunodeficiency virus (HIV)-infected peripheral blood
      mononuclear cells (PBMCs) resulted in transcytosis of infectious virus across the
      trophoblastic monolayer and in productive infection correlating with the fusion
      of HIV-infected PBMCs with trophoblasts. We showed that viral variants are
      selected during these two steps and that in one case of in utero transmission,
      the predominant maternal viral variant characterized after transcytosis was
      phylogenetically indistinguishable from the predominant child's virus. Hence, the
      first steps of transmission of HIV-1 in utero appear to involve the interaction
      between HIV type 1-infected cells and the trophoblastic layer, resulting in the
      passage of infectious HIV by transcytosis and by fusion/infection, both leading
      to a selection of virus quasispecies.

PMID- 11312351
TI  - "Stealth" adenoviruses blunt cell-mediated and humoral immune responses against
      the virus and allow for significant gene expression upon readministration in the
      lung.
AB  - Most of the early gene therapy trials for cystic fibrosis have been with
      adenovirus vectors. First-generation viruses with E1a and E1b deleted are limited
      by transient expression of the transgene and substantial inflammatory responses.
      Gene transfer is also significantly curtailed following a second dose of virus.
      In an effort to reduce adenovirus-associated inflammation, capsids of first
      generation vectors were modified with various activated monomethoxypolyethylene
      glycols. Cytotoxic T-lymphocyte production was significantly reduced in C57BL/6
      mice after a single intratracheal administration of modified vectors, and length
      of gene expression was extended from 4 to 42 days. T-cell subsets from mice
      exposed to the conjugated vectors demonstrated a marked decrease in Th1 responses
      and slight enhancement of Th2 responses compared to animals dosed with native
      virus. Neutralizing antibodies (NAB) against adenovirus capsid proteins were
      reduced in serum and bronchoalveolar lavage fluid of animals after a single dose
      of modified virus, allowing significant levels of gene expression upon
      rechallenge with native adenovirus. Modification with polyethylene glycol (PEG)
      also allowed substantial gene expression from the new vectors in animals
      previously immunized with unmodified virus. However, gene expression was
      significantly reduced after two doses of the same PEG-conjugated vector.
      Alternating the activation group of PEG between doses did produce significant
      gene expression upon readministration. This technology in combination with second
      generation or helper-dependent adenovirus could produce dosing strategies which
      promote successful readministration of vector in clinical trials and marked
      expression in patients with significant anti-adenovirus NAB levels and reduce the
      possibility of immune reactions against viral vectors for gene therapy.

PMID- 11312352
TI  - Visualization of intracellular movement of vaccinia virus virions containing a
      green fluorescent protein-B5R membrane protein chimera.
AB  - We produced an infectious vaccinia virus that expressed the B5R envelope
      glycoprotein fused to the enhanced green fluorescent protein (GFP), allowing us
      to visualize intracellular virus movement in real time. Previous transfection
      studies indicated that fusion of GFP to the C-terminal cytoplasmic domain of B5R
      did not interfere with Golgi localization of the viral protein. To determine
      whether B5R-GFP was fully functional, we started with a B5R deletion mutant that
      made small plaques and inserted the B5R-GFP gene into the original B5R locus. The
      recombinant virus made normal-sized plaques and acquired the ability to form
      actin tails, indicating reversal of the mutant phenotype. Moreover, immunogold
      electron microscopy revealed that both intracellular enveloped virions (IEV) and
      extracellular enveloped virions contained B5R-GFP. By confocal microscopy of live
      infected cells, we visualized individual fluorescent particles, corresponding to
      IEV in size and shape, moving from a juxtanuclear location to the periphery of
      the cell, where they usually collected prior to association with actin tails. The
      fluorescent particles could be seen emanating from cells at the tips of
      microvilli. Using a digital camera attached to an inverted fluorescence
      microscope, we acquired images at 1 frame/s. At this resolution, IEV movement
      appeared saltatory; in some frames there was no net movement, whereas in others
      movement exceeded 2 microm/s. Further studies indicated that IEV movement was
      reversibly arrested by the microtubule-depolymerizing drug nocodazole. This
      result, together with the direction, speed, and saltatory motion of IEV, was
      consistent with a role for microtubules in intracellular transport of IEV.

PMID- 11312353
TI  - Allogeneic transplantation induces expression of cytomegalovirus immediate-early
      genes in vivo: a model for reactivation from latency.
AB  - Reactivation of cytomegalovirus (CMV) from latency is a frequent complication of
      organ transplantation, and the molecular mechanism by which this occurs is
      unknown. Previous studies have shown that allogeneic stimulation induces
      reactivation of human CMV (HCMV) in vitro (64). We find that transplantation of
      vascularized allogeneic kidneys induces murine CMV (MCMV) and HCMV immediate
      early (ie) gene expression. This induction is accompanied by increased expression
      of transcripts encoding inflammatory cytokines, including tumor necrosis factor
      (TNF), interleukin-2, and gamma interferon, and by activation of NF-kappaB. TNF
      alone can substitute for allogeneic transplantation in inducing HCMV and MCMV ie
      gene expression in some tissues. Our studies suggest that reactivation is a
      multistep process which is initiated by factors that induce ie gene expression,
      including TNF and NF-kappaB. Allogeneic transplantation combined with
      immunosuppression may be required to achieve complete reactivation in vivo.

PMID- 11312354
TI  - Interferon action against human parainfluenza virus type 3: involvement of a
      novel antiviral pathway in the inhibition of transcription.
AB  - Interferon (IFN)-induced 2'-5' oligoadenylate synthetase (2-5A synthetase)/RNase
      L, PKR, and Mx proteins are considered to be the principal antiviral protein
      pathways through which IFN induces an antiviral state. It was previously reported
      that human parainfluenza virus type 3 (HPIV3) multiplication was inhibited by IFN
      alpha in human lung epithelial cells A549 and that MxA was found to contribute to
      the inhibition process (Zhao et al., Virology 220:330-338, 1996). Viral primary
      transcription was dramatically inhibited in A549 cells after IFN-alpha treatment,
      but a step following primary transcription was inhibited in U87-MxA cells
      constitutively expressing MxA. Here we have investigated the role of MxA,
      believed to be cell type specific, and other antiviral pathways in the inhibition
      of viral primary transcription. Our data indicate that a novel IFN-induced
      pathway(s) is involved in the inhibition of primary transcription. This is based
      on the following findings: (i) IFN-alpha inhibited viral primary transcription in
      U87-MxA and other cell types including cells lacking MxA; (ii) cells
      constitutively expressing 2-5A synthetase had no antiviral effect against HPIV3;
      and (iii) primary transcription occurred in the absence of protein synthesis, a
      step of PKR target. The novel antiviral pathway(s) was induced by both IFN-alpha
      and IFN-gamma to establish an effective antiviral state against HPIV3. By using
      IFN-alpha-signaling mutant cells, we found that IFN-gamma could elicit antiviral
      effect against HPIV3 without cross talk with the IFN-alpha-signaling pathway.
      These data provide the first evidence that a novel antiviral pathway(s)
      contributes to the antiviral action of IFN against a nonsegmented negative-strand
      RNA virus by targeting the primary transcription.

PMID- 11312355
TI  - Selective excision of AZTMP by drug-resistant human immunodeficiency virus
      reverse transcriptase.
AB  - Two distinct mechanisms can be envisioned for resistance of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to nucleoside
      analogs: one in which the mutations interfere with the ability of HIV-1 RT to
      incorporate the analog, and the other in which the mutations enhance the excision
      of the analog after it has been incorporated. It has been clear for some time
      that there are mutations that selectively interfere with the incorporation of
      nucleoside analogs; however, it has only recently been proposed that zidovudine
      (AZT) resistance can involve the excision of the nucleoside analog after it has
      been incorporated into viral DNA. Although this proposal resolves some important
      issues, it leaves some questions unanswered. In particular, how do the AZT
      resistance mutations enhance excision, and what mechanism(s) causes the excision
      reaction to be relatively specific for AZT? We have used both structural and
      biochemical data to develop a model. In this model, several of the mutations
      associated with AZT resistance act primarily to enhance the binding of ATP, which
      is the most likely pyrophosphate donor in the in vivo excision reaction. The AZT
      resistance mutations serve to increase the affinity of RT for ATP so that, at
      physiological ATP concentrations, excision is reasonably efficient. So far as we
      can determine, the specificity of the excision reaction for an AZT-terminated
      primer is not due to the mutations that confer resistance, but depends instead on
      the structure of the region around the HIV-1 RT polymerase active site and on its
      interactions with the azido group of AZT. Steric constraints involving the azido
      group cause the end of an AZT 5'-monophosphate-terminated primer to
      preferentially reside at the nucleotide binding site, which favors excision.

PMID- 11312356
TI  - Transcription program of human herpesvirus 8 (kaposi's sarcoma-associated
      herpesvirus).
AB  - Human herpesvirus 8 (HHV-8), a gammaherpesvirus implicated in Kaposi's sarcoma,
      primary effusion lymphoma, and Castleman's disease, encodes several
      pathogenically important cellular homologs. To define the HHV-8 transcription
      program, RNA obtained from latently infected body cavity-based lymphoma 1 cells
      induced to undergo lytic replication was used to query a custom HHV-8 DNA
      microarray containing nearly every known viral open reading frame. The patterns
      of viral gene expression offer insights into the replication and pathogenic
      strategies of HHV-8.

PMID- 11312357
TI  - Analysis and characterization of the complete genome of tupaia (tree shrew)
      herpesvirus.
AB  - The tupaia herpesvirus (THV) was isolated from spontaneously degenerating tissue
      cultures of malignant lymphoma, lung, and spleen cell cultures of tree shrews
      (Tupaia spp.). The determination of the complete nucleotide sequence of the THV
      strain 2 genome resulted in a 195,857-bp-long, linear DNA molecule with a G+C
      content of 66.5%. The terminal regions of the THV genome and the loci of
      conserved viral genes were found to be G+C richer. Furthermore, no large
      repetitive DNA sequences could be identified. This is in agreement with the
      previous classification of THV as the prototype species of herpesvirus genome
      group F. The search for potential coding regions resulted in the identification
      of 158 open reading frames (ORFs) regularly distributed on both DNA strands.
      Seventy-six out of the 158 ORFs code for proteins that are significantly
      homologous to known herpesvirus proteins. The highest homologies found were to
      primate and rodent cytomegaloviruses. Biological properties, protein homologies,
      the arrangement of conserved viral genes, and phylogenetic analysis revealed that
      THV is a member of the subfamily Betaherpesvirinae. The evolutionary lineages of
      THV and the cytomegaloviruses seem to have branched off from a common ancestor.
      In addition, it was found that the arrangements of conserved genes of THV and
      murine cytomegalovirus strain Smith, both of which are not able to form genomic
      isomers, are colinear with two different human cytomegalovirus (HCMV) strain
      AD169 genomic isomers that differ from each other in the orientation of the long
      unique region. The biological properties and the high degree of relatedness of
      THV to the mammalian cytomegaloviruses allow the consideration of THV as a model
      system for investigation of HCMV pathogenicity.

PMID- 11312358
TI  - MEK-specific inhibitor U0126 blocks spread of Borna disease virus in cultured
      cells.
AB  - Borna disease virus (BDV) is a highly neurotropic virus that causes Borna
      disease, a virus-induced immune-mediated encephalomyelitis, in a variety of warm
      blooded animals. Recent studies reported that BDV can be detected in patients
      with psychiatric disorders. BDV is noncytopathic, replicates in the nucleus of
      infected cells, and spreads intraaxonally in vivo. Upon infection of susceptible
      cultured cells, virus can be detected in foci. Little is known about the cellular
      components required for BDV replication. Here, we show that the cellular
      Raf/MEK/ERK signaling cascade is activated upon infection with BDV. In the
      presence of the MEK-specific inhibitor U0126, cells get infected with BDV;
      however, there is a block in virus spread to neighboring cells. The effect of the
      inhibitor on virus spread was still observed when the compound was added 2 h
      postinfection but not if treatment was initiated as late as 4 h after infection.
      Our results provide new insights into the BDV-host cell interaction and show that
      virus infection can be controlled with drugs interfering with a cellular
      signaling pathway. Since concentrations of the MEK inhibitor required to block
      BDV focus formation are not toxic for the host cells, our finding may be
      important with respect to antiviral drug development.

PMID- 11312359
TI  - Varicella-zoster virus retains major histocompatibility complex class I proteins
      in the Golgi compartment of infected cells.
AB  - We sought to examine the effects of varicella-zoster virus (VZV) infection on the
      expression of major histocompatibility complex class I (MHC I) molecules by human
      fibroblasts and T lymphocytes. By flow cytometry, VZV infection reduced the cell
      surface expression of MHC I molecules on fibroblasts significantly, yet the
      expression of transferrin receptor was not affected. Importantly, when human
      fetal thymus/liver implants in SCID-hu mice were inoculated with VZV, cell
      surface MHC I expression was downregulated specifically on VZV-infected human
      CD3+ T lymphocytes, a prominent target that sustains VZV viremia. The stage in
      the MHC I assembly process that was disrupted by VZV in fibroblasts was examined
      in pulse-chase and immunoprecipitation experiments in the presence of
      endoglycosidase H. MHC I complexes continued to be assembled in VZV-infected
      cells and were not retained in the endoplasmic reticulum. In contrast,
      immunofluorescence and confocal microscopy showed that VZV infection resulted in
      an accumulation of MHC I molecules which colocalized to the Golgi compartment.
      Inhibition of late viral gene expression by treatment of infected fibroblasts
      with phosphonoacetic acid did not influence the modulation of MHC I expression,
      nor did transfection of cells with plasmids expressing immediate early viral
      proteins. However, cells transfected with a plasmid carrying the early gene ORF66
      did result in a significant downregulation of MHC I expression, suggesting that
      this gene encodes a protein with an immunomodulatory function. Thus, VZV
      downregulates MHC I expression by impairing the transport of MHC I molecules from
      the Golgi compartment to the cell surface; this effect may enable the virus to
      evade CD8+ T-cell immune recognition during VZV pathogenesis, including the
      critical phase of T-lymphocyte-associated viremia.

PMID- 11312360
TI  - In utero infection by porcine reproductive and respiratory syndrome virus is
      sufficient to increase susceptibility of piglets to challenge by Streptococcus
      suis type II.
AB  - Porcine reproductive and respiratory syndrome (PRRS) consistently elevates the
      frequency of disease and mortality in young pigs. Many different secondary
      bacterial diseases occur in PRRS virus (PRRSV)-infected pigs. However, to date,
      establishing a reproducible experimental model of PRRSV infection in weaned pigs,
      with subsequent clinical disease following secondary bacterial challenge, has
      been difficult. PRRSV is frequently isolated during outbreaks from weak-born
      piglets affected by secondary bacterial diseases. This study was performed to
      investigate the potential role of intrauterine PRRSV infection on piglet
      susceptibility to secondary bacterial infection. PRRSV-free pregnant sows were
      intranasally infected at 98 days of gestation with PRRSV strain SD 23983. All
      piglets born to the PRRSV-infected sows were viremic. Piglets were removed from
      the sows at birth and deprived of colostrum. Piglets from PRRSV-infected and
      noninfected sows were randomly assigned to Streptococcus suis challenge or
      control subgroups. At 5 days of age, piglets were challenged intranasally with
      strain MN 87555 of S. suis type II. Total and differential leukocyte counts were
      performed on blood samples collected at 3 days of age. The numbers of leukocytes,
      lymphocytes, and monocytes were significantly reduced in the PRRSV-infected
      piglets. Lesions were observed in bone marrow, brain, lung, heart, spleen, lymph
      node, tonsil, and thymus of PRRSV-infected piglets. Thymus/body weight ratios of
      in utero PRRSV-infected piglets were significantly reduced compared to those of
      non-PRRSV-infected piglets, and thymic lesions were characterized by severe
      cortical depletion of thymocytes. Lesions were not observed in piglets born to
      PRRSV-free sows. Overall, 20 out of 22 piglets in the PRRSV-S. suis dual
      infection group died within 1 week after challenge with S. suis (10 of 11 in each
      of two trials). This contrasts with 1 of 18 piglets in the PRRSV-infection-only
      group and 5 of 23 piglets in the S. suis-challenge-only group (1 of 12 in trial 1
      and 4 of 11 in trial 2). No piglets died in the uninfected control groups. Most
      of the piglets in the PRRSV-S. suis dual-infection group developed suppurative
      meningitis. S. suis type II was recovered from their brains and joints. These
      results indicate that in utero infection by PRRSV makes piglets more susceptible
      to infection and disease following challenge by S. suis type II. In utero
      infection by PRRSV may provide a useful model to study the interaction between
      PRRSV and bacterial coinfections in piglets.

PMID- 11312361
TI  - Immunity to influenza A H9N2 viruses induced by infection and vaccination.
AB  - Avian influenza A H9N2 viruses are widespread among domestic poultry and were
      recently isolated from humans with respiratory illness in China. Two
      antigenically and genetically distinct groups of H9N2 viruses (G1 and G9) are
      prevalent in China. To evaluate a strategy for vaccination, we compared G1 and G9
      viruses for their relative immunogenicity and cross-protective efficacy.
      Infection of BALB/c mice with representative viruses of either group protected
      against subsequent challenge with the homologous or heterologous H9N2 virus in
      the absence of detectable cross-reactive serum hemagglutination inhibition
      antibody. Mice injected intramuscularly with inactivated G1 whole virus vaccine
      were completely protected from challenge with either H9N2 virus. In contrast,
      mice administered inactivated G9 vaccine were only partially protected against
      heterologous challenge with the G1 virus. These results have implications for the
      development of human vaccines against H9N2 viruses, a priority for pandemic
      preparedness.

PMID- 11312362
TI  - Identification of critical elements in the tRNA acceptor stem and T(Psi)C loop
      necessary for human immunodeficiency virus type 1 infectivity.
AB  - A mutant human immunodeficiency virus type 1 (HIV-1) with a primer binding site
      (PBS) complementary to yeast tRNA(Phe) (psHIV-Phe), which relies on exogenous
      yeast tRNA(Phe) as reverse transcription primer, was used to investigate elements
      in the tRNA acceptor stem and T(Psi)C stem-loop required for the tRNA primer
      selection and use in HIV-1 replication. tRNA(Phe) mutants with two- or four
      nucleotide deletions in the 3' end retained the capacity to complement
      replication of psHIV-Phe. tRNA(Phe) mutants with an extended 5' end had reduced
      capacity for complementation, which could be restored by extension of the 3' end
      of these tRNA(Phe) mutants with sequences complementary to the HIV-1 U5 region.
      Further analysis of mutations in the acceptor stem of tRNA(Phe) suggested that an
      intact acceptor stem RNA structure is important for complementation. Analysis of
      single-nucleotide changes in the T(Psi)C stem-loop of tRNA(Phe) revealed an
      unexpected, essential role of this region for rescue of psHIV-Phe.

PMID- 11312363
TI  - Persistence of human immunodeficiency virus type 1-specific cytotoxic T
      lymphocyte clones in a subject with rapid disease progression.
AB  - We longitudinally measured T-cell receptor transcript frequencies of human
      immunodeficiency virus type 1 (HIV-1) specific cytotoxic T lymphocytes (CTL) in
      an individual with rapidly progressive disease and high levels of viremia. CTL
      clones elicited during acute HIV-1 infection were present at the time of death,
      despite absent functional CTL responses, arguing against clonal deletion as a
      mechanism for the decline of CTL responses observed during HIV-1 infection.

PMID- 11312364
TI  - Influenza A virus NEP (NS2 protein) downregulates RNA synthesis of model template
      RNAs.
AB  - The influenza A virus NEP (NS2) protein is an structural component of the viral
      particle. To investigate whether this protein has an effect on viral RNA
      synthesis, we examined the expression of an influenza A virus-like
      chloramphenicol acetyltransferase (CAT) RNA in cells synthesizing the four
      influenza A virus core proteins (nucleoprotein, PB1, PB2, and PA) and NEP from
      recombinant plasmids. Influenza A virus NEP inhibited drastically, and in a dose
      dependent manner, the level of CAT expression mediated by the recombinant
      influenza A virus polymerase. This inhibitory effect was not observed in an
      analogous artificial system in which expression of a synthetic CAT RNA is
      mediated by the core proteins of an influenza B virus. This result ruled out the
      possibility that inhibition of reporter gene expression was due to a general
      toxic effect induced by NEP. Analysis of the virus-specific RNA species that
      accumulated in cells expressing the type A recombinant core proteins and NEP
      showed that there was an important reduction in the levels of minireplicon
      derived vRNA, cRNA, and mRNA molecules. Taken together, the results obtained
      suggest a regulatory role for NEP during virus-specific RNA synthesis, and this
      finding is discussed regarding the biological implications for the virus life
      cycle.

PMID- 11312365
TI  - Echoviruses bind heparan sulfate at the cell surface.
AB  - Some echoviruses (EV) that bind decay-accelerating factor (DAF) also bind cells
      of human and murine origins in a DAF-independent manner. Pretreatment of cells
      with heparinase 1 or heparin blocks the binding of radiolabeled virus to the cell
      surface, and heparin prevents infection of rhabdomyosarcoma cells by certain EV,
      including several low-passage clinical isolates of EV 6 and some EV that do not
      bind DAF. These studies suggest that heparan sulfate may be of in vivo relevance
      as an attachment molecule for EV.

PMID- 11312366
TI  - Transfer of primer binding site-mutated simian immunodeficiency virus vectors by
      genetically engineered artificial and hybrid tRNA-like primers.
AB  - Simian immunodeficiency viruses (SIV) harbor primer binding sites (PBS) matching
      tRNA or tRNA. To study determinants of primer usage in SIV, a SIVmac239-based
      vector was impaired by mutating the PBS to a sequence (PBS-X2) with no match to
      any tRNA. By cotransfection of a synthetic gene encoding a tRNA(Pro)-like RNA
      with a match to PBS-X2, the activity of this vector could be restored to a
      transduction efficiency slightly lower than that of the wild-type vector. A
      vector with a PBS matching tRNA(Pro) was functional at a level slightly below
      that of the wild-type vector, but higher transduction efficiency could be
      obtained by cotransfection of a gene for an engineered tRNA(Pro)-tRNA hybrid with
      a match to PBS-Pro. The importance of tRNA backbone identity was further analyzed
      by complementing the PBS-X2 vector with a gene for a matching x2 primer with a
      tRNA backbone, which led to three- to fourfold-higher titers than those observed
      for the x2 primer with the tRNA(Pro) backbone. In summary, our results
      demonstrate flexibility in PBS and primer usage for SIVmac239, with PBS-primer
      complementarity being the major determinant, in analogy with previous findings
      for murine leukemia viruses and human immunodeficiency virus type 1.

PMID- 11312367
TI  - Differential regulation of Epstein-Barr virus (EBV) latent gene expression in
      Burkitt lymphoma cells infected with a recombinant EBV strain.
AB  - Epstein-Barr virus (EBV)-negative Burkitt lymphomas (BLs) can be infected in
      vitro with prototype EBV strains to study how the virus may affect the phenotype
      of tumor cells. Studies thus far have concentrated on the use of transforming B95
      8 and nontransforming P3HR1 strains. Immunological and phenotypic differences
      between the sublines infected with these two strains were reported. The majority
      of these differences, if not all, can be attributed to the lack of EBNA-2 coding
      sequences in the P3HR1 strain. The recent development of a selectable Akata
      strain has opened up new possibilities for infecting epithelial and T cells as
      well. We infected five EBV-negative BL lines with the recombinant Akata virus.
      Our results indicate that the infected cell lines BL28, Ramos, and DG75 express
      EBNA-1, EBNA-2, and LMP1, the viral proteins associated with type III latency,
      and use both YUK and QUK splices. In contrast, two EBV-negative variants of Akata
      and Mutu when reinfected displayed restricted type I latency and expressed only
      EBNA-1. All clones of infected Mutu cells used the QUK splice exclusively. The
      usage of Qp was observed in a majority of Akata clones. Some Akata clones,
      however, were found to have double promoter usage (Qp and C/Wp) but at 4 months
      after infection did not express EBNA-2. The results demonstrate differential
      regulation of EBV latency in BLs with the same recombinant viral strain and
      suggest that the choice of latency type may be cell dependent. The restricted
      latency observed for infected Akata and Mutu cells indicates that a BL may opt
      for type I latency in the absence of immune pressure as well.

PMID- 11312368
TI  - Characterization of human immunodeficiency virus type 1 in saliva and blood
      plasma by V3-specific heteroduplex tracking assay and genotype analyses.
AB  - The gp120 V3-encoding region of human immunodeficiency virus type 1 (HIV-1) RNA
      derived from the saliva and blood plasma of 11 individuals was characterized by
      heteroduplex tracking assay and sequence analyses. R5-like viral variants were
      identified in both fluids of all subjects. X4-like variants were detected in the
      plasma and/or saliva of three subjects, indicating that X4-like variants are not
      excluded from the saliva compartment. Viral subpopulations were similar in both
      fluids of most subjects, suggesting that HIV-1 in oral fluids and blood may stem
      from a common source. These findings raise the possibility of using saliva as a
      noninvasive fluid for evaluating and monitoring viral evolution in infected
      persons.

PMID- 11312369
TI  - Patient-specific cytotoxic T-lymphocyte cross-recognition of naturally occurring
      variants of a human immunodeficiency virus type 1 (HIV-1) p24gag epitope by HIV-1
      infected children.
AB  - We tested seven human immunodeficiency virus-infected children for their
      cytotoxic T-lymphocyte (CTL) activities towards the p24gag QASQEVKNW epitope and
      its nine variant sequences. Our data confirm that most, but not all, CTL
      responses are broadly cross-specific. For the first time, we show the high
      interpatient variability in cross-recognition of mutant CTL epitopes. These
      interindividual variations in the CTL response to the same epitope should be
      taken into account in the design and the evaluation of vaccines.

PMID- 11312370
TI  - Human immunodeficiency virus type 1-specific immunity after genetic immunization
      is enhanced by modification of Gag and Pol expression.
AB  - Immunity to human immunodeficiency virus virion-like structures or a polyprotein
      has been examined after DNA immunization with Rev-independent expression vectors.
      A Gag-Pol fusion protein stimulated cytotoxic T lymphocyte and antibody responses
      to Gag and Pol, while a Gag-Pol pseudoparticle did not elicit substantial Pol
      responses. This fusion protein may be useful for AIDS vaccines.

PMID- 11312371
TI  - The aetiology of psoriatic arthritis.

PMID- 11312372
TI  - Treatment-induced remission in rheumatoid arthritis patients is characterized by
      a reduction in macrophage content of synovial biopsies.
AB  - OBJECTIVES: To document the change in synovial membrane macrophage and T
      lymphocyte content in rheumatoid arthritis (RA) patients who achieve remission
      induced by disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Arthroscopic
      synovial biopsies were taken from four to seven sites around a knee joint in 13
      patients with RA before and at regular intervals after commencing treatment with
      a DMARD. The cellular content of synovial membrane biopsies taken at regular
      intervals for a period of up to 3 yr after commencing treatment was quantitated
      by routine histopathology and immunohistochemical labelling with anti-macrophage
      (CD68) and anti-T lymphocyte (UCHL-1) antibodies. Synovial biopsies were
      quantitated with a validated semiquantitative scoring system and video image
      analysis. RESULTS: Nine patients obtained clinical remission, as defined by
      American College of Rheumatology (ACR) criteria. The changes that occurred in the
      synovial biopsies included a reduction in lining layer thickness, reduced
      vascularity and cellular infiltrate. The most significant reduction in cellular
      infiltrate was in the lining layer macrophages, with less dramatic change in the
      subintimal macrophage infiltrate. Although there was a reduction in CD45 Ro
      positive T lymphocytes in the synovial membranes of patients who attained ACR
      defined disease remission, it was less significant than the reduction in
      macrophage content of the synovial membranes and tended to plateau at a reduced
      level of T-cell infiltration. CONCLUSIONS: Remission in RA patients is
      characterized by a predominant reduction in macrophage content of the synovial
      membrane, suggesting that current DMARDs may target this cell and its
      inflammatory mediators.

PMID- 11312373
TI  - Amelioration of rat antigen-induced arthritis by liposomally conjugated
      methotrexate is accompanied by down-regulation of cytokine mRNA expression.
AB  - OBJECTIVES: We examined the temporal changes in the expression of interleukin
      1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL
      6) in the rat antigen-induced arthritis (AIA) model and investigated how their
      expression was modulated following disease amelioration by liposomally conjugated
      methotrexate (G-MLV). METHODS: On the day of arthritis induction (day 0), rats
      were treated with a single intra-articular injection of G-MLV, methotrexate
      (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7
      after disease induction, animals from each experimental group were killed. Joint
      tissue was examined histologically and for mRNA expression (IL-6, IL-1beta and
      TNF-alpha) using semiquantitative reverse transcription-polymerase chain
      reaction. RESULTS: There was no significant difference (ANOVA) in knee swelling
      between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G
      MLV significantly reduced knee swelling (1.94+/-0.12 mm; P<0.0001) compared with
      rats treated with MTX (3.17+/-0.18 mm). G-MLV treatment also significantly
      inhibited the histological progression of AIA. This reduction in disease severity
      was accompanied by a reduction in IL-1beta mRNA expression in synovial tissue
      extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7. CONCLUSIONS:
      Liposomally conjugated MTX may exert its beneficial effects in experimental
      arthritis through IL-1beta and IL-6 inhibition.

PMID- 11312374
TI  - Arthroscopic subacromial surgery in inflammatory arthritis of the shoulder.
AB  - OBJECTIVE: To evaluate the effectiveness of shoulder arthroscopy, with
      predominantly subacromial surgery, in patients with inflammatory arthritis.
      METHODS: Twelve patients with inflammatory arthropathy underwent arthroscopic
      shoulder surgery with subacromial decompression, debridement, and limited
      synovectomy. All clinically had symptoms predominantly arising from the
      subacromial region. RESULTS: In the final review, ten patients (83%) were
      satisfied with the result. Two year follow-up was achieved in 11 patients. Seven
      rated their recovery as good or excellent, one was fair, and three were poor. All
      three poor results had fairly advanced glenohumeral chondral damage. CONCLUSION:
      In patients with inflammatory arthropathy and shoulder pain which clinically
      appears related predominantly to the subacromial region, provided there is no
      major chondral damage, then a reasonable result can be expected with arthroscopic
      debridement and modified subacromial decompression.

PMID- 11312375
TI  - Self-efficacy and health status in rheumatoid arthritis: a two-year longitudinal
      observational study.
AB  - OBJECTIVE: To investigate the relationship between baseline level of self
      efficacy for pain and other symptoms and changes in measures for similar
      dimensions of health status over a period of 2 yr in patients with rheumatoid
      arthritis (RA). METHODS: Data collected from patients with RA enrolled in a
      county-based disease register in Oslo, Norway were analysed: 815 patients were
      examined by mail questionnaire in 1994 and again in 1996. Relationships of the
      baseline level of self-efficacy and demographic variables with 2-yr changes in
      health status measures were examined by bivariate and multiple regression
      analysis. The following health status measures were included: pain and fatigue on
      a visual analogue scale; the patient's global assessment of disease activity; the
      symptom and affect scales of the Arthritis Impact Measurement Scales (AIMS2); and
      the bodily pain, mental health, general health and vitality scales of the Short
      Form-36 (SF-36). RESULTS: For all health status measures, there was a significant
      correlation between the change over a 2-yr span and baseline self-efficacy, even
      after adjustment for demographic variables and for the baseline level of the
      health status measure. Favourable changes were associated with high self-efficacy
      scores. CONCLUSIONS: In patients with RA, the baseline levels of self-efficacy
      for pain and other symptoms seem to influence 2-yr changes in health status
      measures regarding these aspects.

PMID- 11312376
TI  - Interleukin-6 promoter polymorphism (--174 G/C) in Caucasian German patients with
      systemic lupus erythematosus.
AB  - BACKGROUND: A biallelic polymorphism (--174 G/C) within the interleukin-6 (IL-6)
      promoter reportedly has functional importance through the modulation of IL-6
      expression in vitro and in vivo. METHODS: We performed a population-based case
      control study to analyse the association of the --174 G/C polymorphism with
      disease susceptibility and clinical manifestations in 211 German patients with
      systemic lupus erythematosus (SLE). RESULTS: There were no significant
      differences in allelic and genotypic frequencies between patients and healthy
      controls. Comparing patients with various disease manifestations, we found an
      association of the --174 G allele with discoid skin lesions (Pc=0.034) and anti
      histone antibodies (Pc=0.009). CONCLUSIONS: The IL-6 promoter polymorphism --174
      G/C does not contribute significantly to disease susceptibility, but predisposes
      to distinct clinical and immunological features. A genetically determined high IL
      6 response may have a pathogenic role under these conditions.

PMID- 11312377
TI  - Antibodies against oxidized low-density lipoproteins in systemic sclerosis.
AB  - OBJECTIVE: To investigate whether circulating concentrations of antibodies
      against oxidized low-density lipoproteins (LDL) are increased in patients with
      systemic sclerosis (SSc). METHODS: Oxidation of LDL and anti-oxidized LDL
      antibodies were measured in 26 patients with limited cutaneous SSc (LCSSc), in
      eight patients with diffuse cutaneous SSc (DCSSc) and in 24 healthy control
      subjects. Results were adjusted for age, sex and smoking. RESULTS: Binding to
      oxidized LDL was increased in patients with both limited and diffuse cutaneous
      disease (geometric mean 0.35 and 0.39 optical density units respectively)
      compared with controls (0.28) (P=0.03 and P=0.01 respectively). Circulating
      concentrations of anti-oxidized LDL were increased only in patients with diffuse
      SSc (geometric mean 0.22 optical density units) compared with controls (geometric
      mean 0.16, P=0.02). CONCLUSION: These preliminary findings lend further weight to
      the concept that oxidation of LDL contributes to the vascular pathology of SSc,
      particularly in patients with diffuse cutaneous disease. Prospective longitudinal
      studies are required to investigate whether anti-oxidized LDL antibodies may be a
      marker of vascular damage in SSC.

PMID- 11312378
TI  - Renal vascular damage in Japanese patients with systemic sclerosis.
AB  - OBJECTIVE: To evaluate renal vascular damage in Japanese patients with systemic
      sclerosis (SSc) by colour-flow Doppler ultrasonography. METHODS: The pulsatility
      index (PI) was measured in renal interlobar and segmental arteries by colour-flow
      Doppler ultrasonography. RESULTS: PI values of interlobar arteries were increased
      in SSc patients (n=53) with normal renal function compared with healthy persons
      (n=16), systemic lupus erythematosus patients (n=12) and dermatomyositis patients
      (n=3). SSc patients with elevated PI levels had digital pitting scar, short
      sublingual frenulum, contracture of phalanges, pulmonary fibrosis, decreased per
      cent vital capacity, heart involvement, positivity for anti-topoisomerase I
      antibody, and elevated C-reactive protein more frequently than those with normal
      PI levels. CONCLUSION: Although renal crisis is rare in Japanese SSc patients,
      our study suggests that latent and subclinical renal damage exists in these
      patients.

PMID- 11312379
TI  - Foot problems in patients with systemic sclerosis.
AB  - OBJECTIVES: To assess the nature of the foot problems experienced in patients
      with systemic sclerosis (SSc) and patient awareness of such problems. METHODS:
      Fifty unselected patients (42 females, eight males) with SSc were assessed by
      means of examination by a senior podiatrist, completion of a questionnaire
      detailing past and present foot problems, determination of random plasma glucose,
      plain X-rays of the feet, and measurement of the ankle/brachial index and of
      digital pulses by Doppler ultrasound. RESULTS: Eighty-six per cent of patients
      reported colour changes in their feet in response to temperature changes, 82%
      reported pain usually related to cold, 26% had suffered foot ulceration and 8%
      had a history of foot surgery. Podiatry assessment confirmed the presence of
      significant abnormalities, including ulcerations in 10%, pre-ulcerative lesions
      in 34%, toenail changes in 62%, callus formation in 80% and calcinosis in 18%.
      Forty per cent of the patients had problems with the fitting of shoes, and 19%
      had been provided with footwear from the hospital. Plain films of the feet
      demonstrated the presence of erosions in 6%, soft-tissue calcification in 17%,
      osteopenia in 26% and degenerative changes in 60% of cases. Ten per cent of the
      patients had an abnormal ankle brachial index (less than 1.0). Only 21% of the 47
      patients in whom digital pulses were examined had normal pulses in all toes, and
      in 26% all toe pulses were absent. CONCLUSION: Although problems with the hands
      are well recognized in SSc, foot problems also occur in the majority of patients,
      and can be a cause of major disability. Care of the feet is therefore an
      important part of the management of SSC.

PMID- 11312380
TI  - Measurement of joint space width in hip osteoarthritis: influence of joint
      positioning and radiographic procedure.
AB  - OBJECTIVES: We assessed the influence of patient positioning and radiographic
      procedure, and defined a smallest detectable difference (SDD) in hip
      osteoarthritis (OA). METHODS: OA hip patients each had a standardized pelvic
      radiograph and, 5 min later, a modified pelvic radiograph with the feet
      internally rotated 5 degrees (part 1 of the study), the X-ray beam centred on the
      umbilicus (part 2), or another standardized pelvic radiograph (part 3). RESULTS:
      Corresponding mean differences in joint space width (JSW) measurements (limits of
      agreement) between views were +0.03 (-0.53 to +0.59), -0.31 (-1.15 to +0.53) and 
      0.02 (-0.48 to +0.44) mm. The two views differed significantly in mean JSW in
      part 2 of the study (P=1.6x10(-4)), but not in part 1 (P=0.375) and part 3
      (P=0.580). The SDD estimate was 0.46 mm. CONCLUSIONS: Modifying the X-ray beam
      and foot rotation increases variability in JSW measurements. Use of urograms to
      evaluate radiological progression should be avoided. A change greater than 0.46
      mm could define radiological hip OA progression.

PMID- 11312381
TI  - Screening for extensor tendon rupture in rheumatoid arthritis.
AB  - OBJECTIVE: Surgery can prevent extensor tendon rupture in the rheumatoid wrist
      but it is difficult to identify patients at risk. Extensor digiti minimi (EDM)
      usually ruptures first, but rupture may pass unnoticed because extensor digitorum
      communis (EDC) extends all four fingers simultaneously. We assessed the value of
      screening for EDM rupture by examining for absent independent extension of the
      little finger in a hospital rheumatoid arthritis population. METHODS: The EDM
      test was performed in 550 previously unoperated wrists. Disease activity, joint
      damage, wrist swelling, tenderness and crepitus were recorded. RESULTS:
      Unsuspected EDM loss was found in nine of the 550 wrists (1.6%); dorsal synovitis
      was absent or minimal in eight and ulnar tenderness was absent in six. EDM loss
      was not associated with activity, severity or duration of disease. CONCLUSIONS:
      The EDM test is simple and cheap. It may identify patients at risk and permit
      prophylactic surgery before hand function is lost.

PMID- 11312382
TI  - Decreased serum erythropoietin and its relation to anti-erythropoietin antibodies
      in anaemia of systemic lupus erythematosus.
AB  - OBJECTIVE: This study was performed to assess erythropoietin levels and anti
      erythropoietin antibodies in patients with systemic lupus erythematosus (SLE).
      METHODS: The sera of 100 patients with SLE were investigated for serum
      erythropoietin levels and the presence of anti-erythropoietin antibodies by
      ELISA. Routine laboratory parameters such as peripheral blood count, relevant
      parameters of blood chemistry, and immunological parameters of SLE were recorded.
      RESULTS: Erythropoietin levels were significantly decreased in SLE patients when
      related to individual haemoglobin and haematocrit values (P<0.001), suggesting an
      inadequate erythropoietin response in SLE. Anti-erythropoietin antibodies were
      found in 46% of SLE patients, and erythropoietin levels (but not haemoglobin or
      haematocrit values) were significantly decreased in these patients compared with
      patients without anti-erythropoietin antibodies. Serum erythropoietin
      concentration as determined by ELISA was reduced in the presence of anti
      erythropoietin antibodies. Furthermore, anti-erythropoietin antibodies also
      correlated with younger age, decreased serum levels of complement factors C3 and
      C4 and elevated anti-double-stranded DNA antibodies. CONCLUSIONS: We conclude
      that the anaemia of SLE is characterized by an inadequate erythropoietin
      response. Anti-erythropoietin antibodies are frequently present in SLE and
      interfere with the measurement of serum erythropoietin level. However, these
      antibodies are not associated with increased severity of SLE-associated anaemia.

PMID- 11312383
TI  - Physical exercise and risk of severe knee osteoarthritis requiring arthroplasty.
AB  - OBJECTIVES: To examine the association between physical exercise and the risk of
      severe knee osteoarthritis requiring arthroplasty. SUBJECTS AND METHODS: A case
      control study was carried out in which the cases were men (n=55) and women aged
      55-75 yr (n=226) receiving knee arthroplasty for primary osteoarthritis at the
      Kuopio University Hospital. Controls (n=524) were selected randomly from the
      population of Kuopio province. Lifetime physical exercise was assessed
      retrospectively. Cumulative exercise hours were calculated and divided into two
      classes by mean (low/high). RESULTS: The risk of knee osteoarthritis requiring
      arthroplasty decreased with increasing cumulative hours of recreational physical
      exercise. After adjustment for age, body mass index, physical work stress, knee
      injury and smoking, the odds ratios (with 95% confidence intervals) of knee
      arthroplasty were 0.91 (0.31-2.63) in men with a low number of cumulative
      exercise hours and 0.35 (0.12-0.95) in those with a high number of cumulative
      exercise hours, with a history of no regular physical exercise as the reference.
      For the women, the corresponding odds ratios were 0.56 (0.3-0.93) and 0.56 (0.32
      0.98). CONCLUSION: Moderate recreational physical exercise is associated with a
      decrease in the risk of knee osteoarthritis.

PMID- 11312384
TI  - Peptidoglycan from sterile human spleen induces T-cell proliferation and
      inflammatory mediators in rheumatoid arthritis patients and healthy subjects.
AB  - OBJECTIVES: Peptidoglycan (PG), a component of Gram-positive bacteria, may be
      involved in rheumatoid arthritis (RA) because of its ability to induce production
      of proinflammatory cytokines, to induce arthritis in rodents, and its presence in
      antigen-presenting cells in RA joints. METHODS: In the present study,
      physiologically relevant PG was able to induce T-cell proliferation in peripheral
      blood and synovial fluid samples of RA patients, but the magnitude of the
      response did not differ from that of cells from healthy subjects. In addition,
      production of cytokines associated with RA (interleukins (IL)-1beta, IL-6, IL-8,
      IL-10, IL-12 and tumour necrosis factor alpha) and of the matrix
      metalloproteinase, gelatinase B (MMP-9), was induced in blood and synovial fluid
      cultures of RA patients. CONCLUSION: The fact that PG, which can be found in
      synovial tissues of RA patients is able to induce the production of inflammatory
      mediators supports the hypothesis that PG plays a role in the pathogenesis of RA
      by influencing the inflammatory microenvironment of the joint.

PMID- 11312385
TI  - Mortality in rheumatoid arthritis: relationship to single and composite measures
      of disease activity.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous disease characterized by
      a variable course of remissions and relapses. Single measures of disease activity
      at only one point in time may not reflect the overall control of disease
      activity. OBJECTIVE: The aim was to determine (i) the predictive value of 20
      baseline demographic and disease variables on mortality, and (ii) the
      relationship between serial measures of the Stoke index (SI; a validated index of
      disease activity in RA) and mortality in RA. METHODS: Mortality in 309 RA
      patients followed up for a median of 14 yr was analysed retrospectively. The
      standardized mortality ratio (SMR) was calculated for all causes of death. The
      predictive values of baseline and time-integrated variables were assessed using
      multivariate Cox proportional hazards regression analysis. RESULTS: The SMR was
      1.65. At baseline, only nodules, erosions, RA latex titre, white cell count and
      globulin level were predictive of mortality after correction for age, sex and
      disease duration. Using a stepwise Cox proportional hazards regression model, the
      most powerful predictors of mortality were age, nodules and RA latex titre.
      Individual measures of disease activity and the SI at baseline were not
      predictive of mortality. However, the mean level of the SI over 12 months was
      related to mortality (P=0.039). CONCLUSIONS: At baseline, the demographic and
      disease variables most significantly related to mortality in RA are age, nodules
      and RA latex titre. Individual measures of disease activity at a single point in
      time are poor predictors of mortality in RA. However, measurement of the mean
      level of disease activity over time using the composite SI has a significant
      relationship with mortality. A high level of sustained inflammation appears to be
      an important predictor of premature death.

PMID- 11312386
TI  - Pulmonary hypertension in systemic sclerosis: risk factors for progression and
      consequences for survival.
AB  - OBJECTIVE: To assess the rate of progression of pulmonary hypertension (PHT) in
      systemic sclerosis (SSc) and its bearing on mortality. METHODS: A retrospective
      record review of 930 patients with SSc attending a specialist centre was carried
      out. Those at risk for both idiopathic and secondary PHT were assessed by serial
      Doppler echocardiography. Mortality data were reviewed. RESULTS: The cumulative
      prevalence of PHT was 13%. Pressures remained static in most cases. The mortality
      among those with a single pressure reading of 30 mmHg or higher was 20% at 20
      months. An increased mortality risk was associated with high initial pressures
      and rising pressures. Rapid pressure rises occurred more frequently in limited
      than in diffuse SSC. CONCLUSIONS: The prevalence of PHT in SSc is high and the
      detection of PHT at any time in the disease course is associated with substantial
      mortality. These results demonstrate the value of echocardiographic screening for
      PHT in all patients with SSC.

PMID- 11312387
TI  - Value of the bell test and the hyperextension test for diagnosis in sciatica
      associated with disc herniation: comparison with Lasegue's sign and the crossed
      Lasegue's sign.
AB  - OBJECTIVES: To evaluate the reliability, sensitivity, specificity and positive
      (PPV) and negative (NPV) predictive values for the diagnosis of sciatica
      associated with disc herniation of the bell test (BT) and the hyperextension test
      (HT). METHODS: According to magnetic resonance imaging, computed tomography
      scanning or myelography findings, patients were classified as having sciatica
      associated with disc herniation (group A) or sciatica without disc herniation or
      sciatica of other mechanical origin (group B). Four clinical manoeuvres [bell
      test (BT), hyperextension test (HT), Lasegue's sign (LS) and the crossed
      Lasegue's sign (CL)] were tested by three investigators. Intra- and interobserver
      reliabilities were calculated using the kappa correlation coefficient or the
      intraclass correlation coefficient (ICC). The sensitivity, specificity, PPV and
      NPV of the four manoeuvres were calculated. Stepwise logistic regression analysis
      was performed to determine the best set of variables predicting sciatica caused
      by disc herniation. RESULTS: Seventy-eight patients (43 in group A, 35 in group
      B; 33 males) with a mean age of 50+/-16 yr were included. Interobserver
      reliabilities ranged from 0.58 to 0.64 for the BT, 0.35 to 0.50 for the HT, 0.27
      to 0.47 for LS and 0.43 to 0.72 for CL. LS had the best sensitivity (0.77-0.83)
      and CL the best specificity (0.74-0.89), while PPV and NPV were equivalent for
      the four manoeuvres (0.55-0.75 for PPV and 0.45-0.59 for NPV). The best PPV was
      observed for the association of HT with CL (0.67-0.85). Stepwise logistic
      regression analysis did not allow us to propose a set of variables predicting
      sciatica caused by disc herniation. CONCLUSION: This study suggests that clinical
      values of the BT and HT are of interest, and are similar to those of LS and CL.

PMID- 11312388
TI  - Nosology versus pathology, two approaches to rheumatic diseases illustrated by
      Alfred Baring Garrod and Jean-Martin Charcot.
AB  - OBJECTIVES: To show why and how, without underestimating the popular perception
      of the word 'rheumatism', a medical approach to rheumatic diseases needs to
      consider the distinction between nosology (the study of diseases) and pathology
      [anatomopathology (the study of lesions) and physiopathology (the study of
      functional disturbances)]. METHODS: Selected quotations reflecting the thought
      processes of two famous physicians whose clinical activity (orientated towards
      nosology) was firmly based on pathology (mainly physiopathology in the case of A.
      B. Garrod and mainly anatomopathology in the case of J.-M. Charcot) are
      discussed. RESULTS: Starting from the physiopathological criterion of
      hyperuricaemia in gout, Garrod's thought processes led him to name and study
      rheumatoid arthritis. Alongside his neurological work, Charcot's thought
      processes led him to underline the common anatomical changes which could be
      observed in some nosologically distinct forms of chronic rheumatism. CONCLUSIONS:
      Selected older texts of both authors provide good examples of a methodology which
      can still be useful for present-day rheumatologists, particularly during their
      training period. They could serve as a guide to clarify some semantic ambiguities
      concerning nosology and pathology and for a better understanding of some clinical
      and radiological overlaps between distinct nosological entities.

PMID- 11312389
TI  - Abdominal aortic aneurysm with lumbar vertebral erosion in Behcet's disease
      revealed by low back pain: a case report and review of the literature.

PMID- 11312390
TI  - Treatment of recalcitrant orogenital ulceration of Behcet's syndrome with
      infliximab.

PMID- 11312391
TI  - Correlation of circulating interleukin 16 with proinflammatory cytokines in
      patients with rheumatoid arthritis.

PMID- 11312392
TI  - Stromelysin promoter polymorphism is associated with systemic sclerosis.

PMID- 11312393
TI  - Pneumomediastinum and subcutaneous emphysema associated with dermatomyositis.

PMID- 11312394
TI  - Sclerosant injections for low back pain.

PMID- 11312396
TI  - The labyrinth of asthma phenotypes and exhaled NO.

PMID- 11312397
TI  - COX-2 expression in asthmatic airways: the story so far.

PMID- 11312398
TI  - Sarcoidosis: old and new treatments.

PMID- 11312399
TI  - Good respiratory practice in primary care.

PMID- 11312400
TI  - Degranulation patterns of eosinophil granulocytes as determinants of eosinophil
      driven disease.
AB  - BACKGROUND: Degranulation of eosinophils in target tissues is considered a key
      pathogenic event in major chronic eosinophilic diseases. However, because of a
      lack of appropriate methods, little is known about degranulation of eosinophils
      in common eosinophilic diseases. METHODS: Using transmission electron microscopic
      (TEM) analysis, a novel approach has been devised and validated to quantify
      eosinophil degranulation in human tissues (assessed in individual cells as
      percentage granules with structural signs of protein release). Biopsy specimens
      from patients with inflammatory bowel disease, allergic rhinitis, asthma, and
      nasal polyposis were evaluated. RESULTS: All conditions displayed a similar
      degree of local tissue eosinophilia, with no differences being observed in
      eosinophil numbers in the airway mucosa of patients with airway diseases and the
      colonic mucosa of those with inflammatory bowel disease (IBD). In contrast,
      marked differences in the mean (SE) extent of eosinophil degranulation were
      observed between the patient groups; IBD 9.3 (1.4)% altered granules, artificial
      and natural allergen challenge induced allergic rhinitis 67.8 (6.8)% and 86.6
      (3.0)%, respectively, asthma 18.1 (2)%, and nasal polyposis 46.6 (7.6)%.
      CONCLUSIONS: This study provides the first quantitative data which show that
      different eosinophilic conditions, despite having similar numbers of tissue
      eosinophils, may exhibit markedly different degranulation patterns. The present
      assessment of piecemeal degranulation would thus make it possible to delineate
      the conditions under which eosinophils are likely to contribute to disease
      processes. This novel type of analysis may also guide and validate anti
      eosinophilic treatment options.

PMID- 11312401
TI  - Evidence for different subgroups of difficult asthma in children.
AB  - BACKGROUND: Children with difficult asthma experience frequent symptoms despite
      treatment with high dose inhaled steroids. Persistent symptoms may result from
      persistent airway inflammation which can be monitored by measuring exhaled nitric
      oxide (NO). This study aimed to assess the role of airway inflammation, using NO
      as a surrogate, in children with difficult asthma and to investigate the response
      to oral prednisolone. METHODS: NO was measured in 23 children (mean age 11.7
      years) with difficult asthma, before and after 2 weeks of treatment with oral
      prednisolone. The clinical response was assessed by spirometric tests, peak flow,
      bronchodilator use, and symptoms. Adherence to treatment was assessed by
      measuring serum prednisolone and cortisol concentrations. NO was measured in 55
      healthy children to establish a normal range. RESULTS: NO concentrations were
      higher in asthmatic patients than in controls (geometric mean 11.2 v 5.3 ppb,
      p<0.01). Using grouped data, the concentration of NO fell following prednisolone
      (11.2 v 7.5 ppb, p<0.01) accompanied by an improvement in morning peak flow
      (p<0.05). The baseline NO concentration was raised (>12.5 ppb) in nine asthmatic
      patients and remained high after prednisolone in five. Thirteen had normal levels
      of NO (<12.5 ppb) before and after prednisolone. Thirteen asthmatic patients
      remained symptomatic following prednisolone; NO levels were raised on both
      occasions in five of these and were normal in seven. CONCLUSIONS: As a group, the
      asthmatic subjects demonstrated evidence of airway inflammation which responded
      to prednisolone. At least two subgroups of patients were identified: one with
      persistently raised NO levels despite treatment with oral prednisolone indicating
      ongoing steroid insensitive inflammation, and another with normal levels of NO.
      Both subgroups included patients with persistent symptoms, which suggests that
      different patterns of difficult asthma in children exist.

PMID- 11312402
TI  - Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in
      the airway epithelium of asthmatic subjects and regulation by corticosteroid
      treatment.
AB  - BACKGROUND: Nitric oxide (NO) and prostanoids are mediators of vascular and
      bronchial tone that are postulated to be involved in asthma. Increased levels of
      both are found in asthmatic subjects and are synthesised by enzymes that have
      cytokine inducible forms: inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX
      2), respectively. We hypothesised that the in vivo expression of iNOS and COX-2
      in the airways would be increased in asthma, and that these cytokine inducible
      enzymes may represent targets for regulation by corticosteroid treatment.
      METHODS: Bronchial biopsy specimens were obtained from three groups of subjects:
      atopic asthmatics treated with beta(2) agonists alone (n=7), atopic asthmatics
      additionally receiving regular treatment with corticosteroids (n=8), and non
      asthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA and
      immunoreactive protein was studied using in situ hybridisation and quantitative
      immunohistochemistry. RESULTS: Immunoreactivity and the hybridisation signal for
      iNOS and COX-2 were mainly localised in the airway epithelium. The proportion of
      epithelium immunostained was significantly greater in the non-steroid treated
      asthmatic subjects (iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid
      treated asthmatics (iNOS 3.4 (1.0)%, p=0.009; COX-2 13.0 (0.6)%, p=0.0015) or the
      non-asthmatic controls (iNOS 4.2 (0.9)%, p=0.018; COX-2 11.6 (0.6)%, p=0.0003).
      Similarly, the hybridisation signal was stronger in the non-steroid treated group
      of asthmatic subjects than in the other two groups. CONCLUSIONS: These findings
      highlight the potential role of the airway epithelium both as a contributor to
      the inflammatory process in asthma and as a target for inhaled corticosteroid
      treatment in this disease.

PMID- 11312403
TI  - Short term variability of single breath carbon monoxide transfer factor.
AB  - BACKGROUND: When monitoring patients with chronic lung disease it is important to
      distinguish genuine changes in gas transfer over time from natural variability.
      This study aims to define the coefficient of repeatability for routine
      measurements of single breath transfer factor (TCO) and transfer coefficient
      (KCO). METHODS: Sixty eight subjects (32 with emphysema, 36 healthy volunteers)
      had TCO measured twice at a mean (SD) interval of 7.5 (1.3) days. On each
      occasion a standard protocol (conforming to BTS guidelines) was followed,
      comprising duplicate measurements satisfying standard technical criteria. The
      mean of these duplicates was recorded. For the pooled data changes in TCO and KCO
      between study days were expressed as coefficient of repeatability. RESULTS: The
      coefficient of repeatability was +/-1.60 mmol/min/kPa for TCO and +/-0.24
      mmol/min/kPa/l for KCO. Correcting TCO and KCO for prevailing barometric pressure
      or carboxyhaemoglobin level made no significant difference to the results.
      CONCLUSIONS: The quoted limits for variability in gas transfer over time are
      valid for a wide range of clinically relevant values. Changes in TCO and KCO
      greater than these limits are unlikely to arise from natural variation.

PMID- 11312404
TI  - Repeatability of bronchial hyperresponsiveness to adenosine-5'-monophosphate
      (AMP) by a short dosimeter protocol.
AB  - BACKGROUND: To study bronchial responsiveness to adenosine 5'-monophosphate (AMP)
      in population surveys, repeatability of a rapid dosimetric method with
      quadrupling doses was evaluated. METHODS: Volunteers with symptoms of airway
      respiratory allergy or asthma were invited for AMP challenges on two occasions.
      After each dose the fall in forced expiratory volume in one second (FEV(1))
      compared with the post-saline value was determined. The cumulative doses of AMP
      needed to cause a fall in FEV(1) of 20% (PD(20)), 15% (PD(15)), and 10% (PD(10))
      were calculated. Agreement was evaluated by means of kappa values. After
      excluding systematic differences in PD values on two occasions (t test),
      repeatability of a single estimation of the chosen PD values was calculated and
      expressed in doubling doses (DD). RESULTS: In 28 of 76 subjects a PD(20) was
      estimated on the two visits, in 29 subjects a PD(15) was estimated, and in 32 a
      PD(10) was obtained. Kappa values for a positive threshold were 0.89 for a cut
      off level for a 20% fall in FEV(1), 0.78 for a 15% fall in FEV(1), and 0.76 for a
      fall in FEV(1) of 10%. The PD values did not differ between the two visits and
      95% repeatability of a single estimation was +/-1.7 DD for PD(20), +/-2.2 DD for
      PD(15), and +/-2.4 DD for PD(10). The quadrupling dose method reduced time by 40%
      in non-hyperresponsive subjects and no adverse effects were observed. CONCLUSION:
      The short dosimeter protocol with quadrupling doses for AMP challenges is a
      rapid, reproducible tool for estimating bronchial responsiveness in population
      surveys.

PMID- 11312405
TI  - Assessment of airway neutrophils by sputum colour: correlation with airways
      inflammation.
AB  - BACKGROUND: Airway inflammation, with recruitment of neutrophils to the airway
      lumen, results in purulent secretions and a variety of potential adverse
      consequences for patients with chronic bronchitis and bronchiectasis. We
      hypothesised that gradations of sputum colour would correlate directly with the
      myeloperoxidase content of sputum and with various other indicators of the
      activity and consequences of bronchial diseases. METHODS: To test this
      hypothesis, we quantified sputum colour by reference to a sensitive nine point
      colour chart and correlated this assessment with indices of a number of
      inflammatory mediators in sputum. RESULTS: The results indicate that standardised
      visual measurements of sputum colour correlated strongly with myeloperoxidase,
      interleukin 8, leucocyte elastase (both activity and total quantity), sputum
      volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for
      all). In addition, there was a strong direct correlation between leucocyte
      elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a
      strong negative correlation with secretory leucocyte proteinase inhibitor
      (p<0.001). CONCLUSIONS: These results indicate that sputum colour graded visually
      relates to the activity of the underlying markers of bronchial inflammation. The
      results of this simple visual analysis of sputum provides guidance concerning
      underlying inflammation and its damaging potential. It also provides a useful
      scientific tool for improving the monitoring of chronic airways diseases and
      response to treatment.

PMID- 11312406
TI  - Respiratory intensive care units in Italy: a national census and prospective
      cohort study.
AB  - BACKGROUND: In Italy, respiratory intensive care units (RICUs) provide an
      intermediate level of care between the intensive care unit (ICU) and the general
      ward for patients with single organ respiratory failure. Because of the lack of
      official epidemiological data in these units, a two phase study was performed
      with the aim of describing the work profile in Italian RICUs. METHODS: A national
      survey of RICUs was conducted from January to March 1997 using a questionnaire
      which comprised over 30 items regarding location, models of service provision,
      staff, and equipment. The following criteria were necessary for inclusion of a
      unit in the survey: (1) a nurse to patient ratio ranging from 1:2.5 to 1:4 per
      shift; (2) availability of adequate continuous non-invasive monitoring; (3)
      expertise for non-invasive ventilation (NIV) and for intubation in case of NIV
      failure; (4) physician availability 24 hours a day. Between November 1997 and
      January 1998 a 3 month prospective cohort study was performed to survey the
      patient population admitted to the RICUs. RESULTS: Twenty six RICUs were included
      in the study: four were located in rehabilitation centres and 22 in general
      hospitals. In most, the reported nurse to patient ratio ranged from 1:2 to 1:3,
      with 36% of units reporting a ratio of 1:4 per shift. During the study period 756
      consecutive patients of mean (SD) age 68 (12) years were admitted to the 26
      RICUs. The highest proportion (47%) were admitted from emergency departments, 19%
      from other medical wards, 18% were transferred from the ICU, 13% from specialist
      respiratory wards, and 2% were transferred following surgery. All but 32 had
      respiratory failure on admission. The reasons for admission to the RICU were:
      monitoring for expected clinical instability (n=221), mechanical ventilation
      (n=473), and weaning (n=59); 586 patients needed mechanical ventilation during
      their stay in the RICU, 425 were treated with non-invasive techniques as a first
      line of treatment (374 by non-invasive positive pressure, 51 by iron lung), and
      161 underwent invasive mechanical ventilation (63 intubated, 98 tracheostomies).
      All but 48 patients had chronic respiratory disease, mainly chronic obstructive
      pulmonary disease (COPD; n=451). More than 70% of patients (n=228) had
      comorbidity, mainly consisting of heart disorders. The median APACHE II score was
      18 (range 1--43). The predicted inpatient mortality risk rate according to the
      APACHE II equation was 22.1% while the actual inpatient mortality rate was 16%.
      The mean length of stay in the RICU was 12 (11) days. The outcome in most
      patients (79.2%) admitted to RICUs was favourable. CONCLUSIONS: Italian RICUs are
      specialised units mainly devoted to the monitoring and treatment of acute on
      chronic respiratory failure by non-invasive ventilation, but also to weaning from
      invasive mechanical ventilation. The results of this study provide a useful
      insight into an increasingly important field of respiratory medicine.

PMID- 11312407
TI  - Pulmonary infiltrates in non-HIV immunocompromised patients: a diagnostic
      approach using non-invasive and bronchoscopic procedures.
AB  - BACKGROUND: The development of pulmonary infiltrates is a frequent life
      threatening complication in immunocompromised patients, requiring early diagnosis
      and specific treatment. In the present study non-invasive and bronchoscopic
      diagnostic techniques were applied in patients with different non-HIV
      immunocompromised conditions to determine the aetiology of the pulmonary
      infiltrates and to evaluate the impact of these methods on therapeutic decisions
      and outcome in this population. METHODS: The non-invasive diagnostic methods
      included serological tests, blood antigen detection, and blood, nasopharyngeal
      wash (NPW), sputum and tracheobronchial aspirate (TBAS) cultures. Bronchoscopic
      techniques included fibrobronchial aspirate (FBAS), protected specimen brush
      (PSB), and bronchoalveolar lavage (BAL). Two hundred consecutive episodes of
      pulmonary infiltrates were prospectively evaluated during a 30 month period in 52
      solid organ transplant recipients, 53 haematopoietic stem cell transplant (HSCT)
      recipients, 68 patients with haematological malignancies, and 27 patients
      requiring chronic treatment with corticosteroids and/or immunosuppressive drugs.
      RESULTS: An aetiological diagnosis was obtained in 162 (81%) of the 200 patients.
      The aetiology of the pulmonary infiltrates was infectious in 125 (77%) and non
      infectious in 37 (23%); 38 (19%) remained undiagnosed. The main infectious
      aetiologies were bacterial (48/125, 24%), fungal (33/125, 17%), and viral
      (20/125, 10%), and the most frequent pathogens were Aspergillus fumigatus (n=29),
      Staphylococcus aureus (n=17), and Pseudomonas aeruginosa (n=12). Among the non
      infectious aetiologies, pulmonary oedema (16/37, 43%) and diffuse alveolar
      haemorrhage (10/37, 27%) were the most common causes. Non-invasive techniques led
      to the diagnosis of pulmonary infiltrates in 41% of the cases in which they were
      used; specifically, the diagnostic yield of blood cultures was 30/191 (16%);
      sputum cultures 27/88 (31%); NPW 9/50 (18%); and TBAS 35/55 (65%). Bronchoscopic
      techniques led to the diagnosis of pulmonary infiltrates in 59% of the cases in
      which they were used: FBAS 16/28 (57%), BAL 68/135 (51%), and PSB 30/125 (24%).
      The results obtained with the different techniques led to a change in antibiotic
      treatment in 93 cases (46%). Although changes in treatment did not have an impact
      on the overall mortality, patients with pulmonary infiltrates of an infectious
      aetiology in whom the change was made during the first 7 days had a better
      outcome (29% mortality) than those in whom treatment was changed later (71%
      mortality; p=0.001). CONCLUSIONS: Non-invasive and bronchoscopic procedures are
      useful techniques for the diagnosis of pulmonary infiltrates in immunocompromised
      patients. Bronchial aspirates (FBAS and TBAS) and BAL have the highest diagnostic
      yield and impact on therapeutic decisions.

PMID- 11312408
TI  - Pulmonary function in adolescent idiopathic scoliosis: a 25 year follow up after
      surgery or start of brace treatment.
AB  - BACKGROUND: Pulmonary function in patients with adolescent idiopathic scoliosis
      many years after posterior spinal surgery or brace treatment has not been
      documented. METHODS: A consecutive group of patients treated by posterior fusion
      or a brace at least 20 years previously was investigated. 90% attended a clinical
      follow up. Lung volumes were determined before treatment in 251 patients, 1.4
      years after surgery in 141 patients, and 25 years after surgery or start of brace
      treatment in 110 patients. Vital capacity (VC) was calculated as percentage
      predicted according to height and age and the results were corrected for loss of
      height due to scoliosis. Scoliosis angles were measured and smoking habits were
      recorded. An age and sex matched control group was also examined with the same
      questionnaire and pulmonary function tests. RESULTS: VC increased from 67%
      predicted immediately before surgery to 73% (p<0.001) after surgery and to 84%
      (p<0.001) at the present follow up, mean change 10.8% (95% CI 9.5 to 12.1). In
      the brace treated patients VC increased from 77% predicted before treatment to
      89% (p<0.001) 25 years after start of treatment, mean change 12.3% (95% CI 10.5
      to 14.1). The mean Cobb angle at the present follow up study was 40 degrees in
      both surgically and brace treated patients. The present results of lung volumes
      did not correlate with pretreatment or post-treatment Cobb angles or smoking
      habits. CONCLUSIONS: Patients treated by posterior fusion or a brace gradually
      increase their pulmonary function up to 25 years after treatment. Smoking and
      curve size are not risk factors for reduced pulmonary function.

PMID- 11312409
TI  - Enhanced inhibition of lymphocyte activation by Mycobacterium avium complex in
      human T lymphotrophic virus type I carriers.
AB  - BACKGROUND: We have previously reported that disseminated pulmonary Mycobacterium
      avium complex (MAC) infection is more common in human T lymphotrophic virus type
      I (HTLV-I) carriers than in non-carriers. However, the reason for this remains
      unclear. It has been shown that glycopeptidelipid (GPL), one of the lipid
      components of the cell envelope of MAC, is able to reduce the lymphocyte
      blastogenic response to mitogens. The purpose of this study was to clarify
      whether or not the inhibitory effect of GPL differs between HTLV-I carriers and
      non-carriers. METHODS: Peripheral blood lymphocytes were obtained from 29
      patients who had recovered from pulmonary MAC infection (10 of whom also had HTLV
      I infection) and the lymphocyte counts and T cell subpopulations of the
      peripheral blood lymphocytes in HTLV-I carriers and non-carriers were compared.
      The inhibitory effect of GPL on the lymphocyte blastogenic response to
      phytohaemagglutinin (PHA) was tested in these 29 cases and in 15 healthy controls
      who had never suffered from MAC (seven of whom also had HTLV-I infection). All
      HTLV-I positive cases were carriers. RESULTS: There was no significant difference
      in the numbers or subset proportions of T cells between HTLV-I carriers and non
      carriers. Lymphocyte activation by PHA was significantly inhibited by GPL in MAC
      positive and negative HTLV-I carriers compared with MAC negative non-carriers and
      MAC negative healthy controls (p<0.001). CONCLUSIONS: We suggest that MAC
      infection leads to strong inhibition of lymphocyte activation in HTLV-I carriers.
      This may account, in part, for the severity of pulmonary MAC infection in HTLV-I
      carriers.

PMID- 11312410
TI  - Pneumonia and pregnancy.

PMID- 11312411
TI  - Continuing the debate about measuring asthma in population studies.
AB  - The reasons for measuring atopy and airway hyperresponsiveness (AHR) and the
      methods of validating measurements of asthma in population studies continue to be
      debated. The debate has centred around standards against which to validate asthma
      measurements but the absence of a "gold standard" makes the criterion validation
      of measurements difficult. Questionnaires will always be useful but cannot be
      validated against a doctor diagnosis because of self-selection and recall biases.
      In practice, measurements should be selected on the merits of what they measure
      rather than being regarded as validated or non-validated alternatives. The
      measurement of AHR is invaluable because it is reliable, not influenced by
      variations in symptom perception or diagnostic trends, and is closely related to
      the underlying mechanisms of asthma. The value of AHR lies in its high
      specificity (rate of true negatives) and low sensitivity (rate of false
      positives) against asthma symptoms which gives additional information about
      symptomatic subjects. Atopy is also a useful test and, in quantifying its
      association with asthma, we should not place any currency on ecological evidence.
      Atopy is a strong risk factor for asthma in the presence of regionally specific
      allergens and ecological analyses that ignore these effects are diversionary
      rather than productive. For preventing asthma, we need to identify the group at
      greatest risk of developing it, measure the risk factors with precision, and
      develop interventions that are effective in changing environmental exposures and
      homogeneous outcomes. This is the only approach that has the potential to lead to
      significant public health benefits.

PMID- 11312412
TI  - British Thoracic Society Winter Meeting 2000.

PMID- 11312413
TI  - Successful use of high dose rate brachytherapy for non-malignant bronchial
      obstruction.
AB  - High dose rate (HDR) endobronchial brachytherapy is a palliative treatment for
      symptomatic airway obstruction by malignant tumours. We report a novel use of HDR
      brachytherapy for treating non-malignant bronchial obstruction. The patient had a
      metal stent placed in a reconstructed airway after a bronchial tear to ensure
      patency. Granulation tissue formation in and around the stent caused symptomatic
      occlusion of the airway, necessitating multiple laser applications. A single
      treatment of HDR brachytherapy (1000 cGy) was delivered following laser therapy.
      The patient remains well 15 months after treatment with no evidence of recurrent
      granulation tissue formation on bronchoscopy. HDR brachytherapy is an effective
      treatment for non-malignant airway obstruction.

PMID- 11312415
TI  - Reduced oxygen uptake during steady state exercise after 21-day mountain climbing
      expedition to 6,194 m.
AB  - We investigated the effect of a 21-day climbing expedition to 6,194 m on the
      oxygen uptake (V022) and leg blood flow (LBF) responses to submaximal exercise in
      five healthy, fit men during two-leg kicking exercise a 0-W and 50-W. Tests were
      completed 1 week before and 3 days after altitued acclimatization. The adaptation
      of VO2 at exercise onset was described by the time to 63% of the new steady
      state. Steady state VO2 during 50-W exercise was less post-climb (1290+/- 29
      mL/min, mean +/- SE) than pre-climb (1413+/- 63 mL/min, P <.05). VO2 adapted more
      slowly at the onset of 50-W exercise post climb. There were no differences in the
      steady state LBF during the 50-W exercise, the increase above baseline, or the
      adaptation post-climb. Respiratory exchange ratio was greater at 50-W post-climb
      compared to pre-climb. Reduced steady state V02 during exercise after exposure to
      high altitude is consistent with an increase in metabolic efficiency.

PMID- 11312416
TI  - The effects of changes in musculoskeletal fitness on health.
AB  - The objective of this review is to examine the effects of changes in the
      individual components of musculoskeletal fitness on indicators of health status.
      Available evidence regarding the impact of changes in musculoskeletal fitness on
      indicators of health status is summarized and evaluated. Intervention programs
      designed specifically to enhance musculoskeletal fitness have been effective in
      improving several indicators of health status including glucose metabolism,
      obesity, bone health, independent living, the incidence of falling and associated
      injuries, and/or psychological well-being. An enhanced musculoskeletal fitness is
      associated with an improvement in health status.

PMID- 11312417
TI  - Musculoskeletal fitness and health.
AB  - The purpose is to examine the relationship between musculoskeletal fitness and
      health status. Muscular strength is positively associated with independence and
      overall quality of life, and negatively associated with morbidity and potentially
      premature mortality. Muscular endurance is positively related to overall quality
      of life. Elevated muscular endurance may reduce the incidence of falling and its
      associated injuries. Muscular power is predictive of functional capacity,
      resultant disability, and potentially premature mortality. Flexibility is
      positively associated with mobility and independence. Women and the aged may be
      susceptible to musculoskeletal impairments leading to reduced health status and
      thus may represent primary target groups for intervention programs. High levels
      of musculoskeletal fitness are associated with positive health status, and low
      levels of musculoskeletal fitness are associated with lower health status.

PMID- 11312418
TI  - Sarcoidosis.
AB  - Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin.
      The cutaneous manifestations of sarcoidosis often enable the dermatologist to be
      the first physician to make the diagnosis. This article reviews essential
      sarcoidosis pathophysiology, clinical polymorphisms, systemic evaluation, and
      treatment modalities for cutaneous sarcoidosis to further enhance the
      dermatologist's understanding of this disease entity. LEARNING OBJECTIVE: At the
      conclusion of this learning activity, participants should be familiar with the
      theories of the pathogenesis of sarcoidosis, its cutaneous manifestations, its
      various syndromes and associations, and its presentation in children.
      Participants should also be more knowledgeable about diagnostic evaluation,
      measurement of disease progression, treatment modalities, and the prognosis and
      mortality data of sarcoidosis.

PMID- 11312419
TI  - Diffuse melanosis arising from metastatic melanoma: pathogenetic function of
      elevated melanocyte peptide growth factors.
AB  - The origin of diffuse melanosis resulting from metastatic melanoma is unknown. We
      examined the light microscopic and ultrastructural changes in the skin of an
      affected 35-year-old woman and determined the peripheral blood levels of
      melanocyte growth factors. A total of 7 biopsy specimens were examined by light
      and electron microscopy and immunohistology (S-100, HMB45, MART1, CD68, MAC387).
      Serum/plasma levels of melanocyte growth factors of the patient were determined
      by enzyme-linked immunosorbent assays and compared with those of normal
      volunteers (n = 10) and amelanotic patients with metastatic melanoma (n = 10),
      matched to the UICC stage of the affected patient. Hyperpigmented but otherwise
      apparently normal skin of the patient displayed epidermal melanocyte hyperplasia,
      increased melanogenesis, and dermal pigment stored in histiocytes and other cells
      along with extracellular deposits. Blood levels of alpha-melanocyte stimulating
      hormone, hepatocyte growth factor, and endothelin-1 were significantly elevated
      in the affected patient. Aberrant production of these factors may not only be
      responsible for activation of the pigment system in diffuse melanosis of
      metastatic melanoma, but also for increased proliferation, motility, and pigment
      incontinence of normal and malignant melanocytes.

PMID- 11312420
TI  - The risk of melanoma in association with long-term exposure to PUVA.
AB  - BACKGROUND: Oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is a
      highly effective therapy for psoriasis and many other skin conditions. It is
      carcinogenic. Previously we reported an increased risk of melanoma that first
      emerged 15 years after first treatment. OBJECTIVE: Our purpose is to present
      additional data concerning the associations of previous exposure to PUVA, the
      passage of time, and the risk of malignant melanoma. METHODS: We have
      prospectively studied a cohort of 1380 patients first treated with PUVA in 1975
      and 1976. We have documented the occurrence of melanoma and in this report
      compare the observed and expected incidence of melanoma in this cohort,
      particularly melanomas developing since our earlier report (ie, after March
      1996). RESULTS: Since 1975, 23 patients have developed 26 invasive or in situ
      cutaneous melanomas. In an average of 2.25 years since our last report, we
      detected 7 additional invasive melanomas (incidence rate ratio, 8.4; 95%
      confidence interval, 3.4-17.3). CONCLUSION: Beginning 15 years after first
      exposure to PUVA, an increased risk of melanoma is observed in our cohort of PUVA
      treated patients. This risk is greater in patients exposed to high doses of PUVA,
      appears to be increasing with the passage of time, and should be considered in
      determining the risks and benefits of this therapy.

PMID- 11312421
TI  - Sentinel lymph node micrometastasis and other histologic factors that predict
      outcome in patients with thicker melanomas.
AB  - BACKGROUND: In patients with melanoma, lymph node staging information is
      obtainable by the surgical techniques of lymphatic mapping and sentinel lymph
      node (SLN) biopsy. Although no survival benefit has been proven for the
      procedure, the staging information is useful in identifying patients who may
      benefit from further surgery or adjuvant therapy. Currently, however, it is not
      being recommended for patients with thick melanomas (> 3-4 mm). The risk of
      hematogenous dissemination is considered too great in these patients. Recent
      studies indicate, however, that a surprising number of patients with thick
      melanomas become long-term survivors, and the lymph node status may be
      predictive. None of the conventional microscopic features used to gauge prognosis
      in patients with melanoma have proven helpful in distinguishing the survivors
      with thick melanoma from those who will die of their disease. OBJECTIVE: Our
      purpose was to evaluate the influence of SLN histology and other microscopic
      parameters on survival of patients with thick melanomas. METHODS: A computerized
      patient database at the Cutaneous Oncology Clinic at H. Lee Moffitt Cancer Center
      was accessed to obtain records on patients with melanomas thicker than 3.0 mm
      (AJCC T3b). A retrospective analysis was conducted with attention paid to
      histologic variables, sentinel node status, and survival. Survival curves were
      constructed with the Kaplan-Meier method, and a Cox-Mantel rank testing was used
      to establish statistical significance. RESULTS: Between 1991 and 1999, 201
      patients were diagnosed with melanoma thicker than 3.0 mm, and 180 were alive at
      an average follow-up of 51 months. Of these, 166 were alive without disease. The
      mean overall and disease-free survival rates were 78% and 66%, respectively.
      There was a statistically significant difference in disease-free survival (3
      year) between SLN-positive and SLN-negative patients (37% vs 73%, respectively; P
      =.02). The overall survival (3-year) for the SLN-positive patients was less than
      the node-negative patients (70% vs 82%), but it was not statistically significant
      (P =.08). The disease-free survival for patients with ulcerated lesions was less
      than for nonulcerated lesions (77% vs 93%, P =.05). None of the other histologic
      parameters studied, including Breslow thickness, Clark level, mitotic rate, or
      regression, had an influence on the overall or disease-free survival in this
      group of patients with thick tumors. CONCLUSIONS: The results indicate that the
      SLN node status is predictive of disease-free survival for patients with thick
      melanomas. A surprising number of patients in the study were free of disease
      after prolonged follow-up. None of the histologic features of the primary tumor
      were helpful in predicting outcome, except for ulceration. SLN biopsy appears to
      be justified for prognostic purposes in patients with thick melanomas.

PMID- 11312422
TI  - Reduction of ultraviolet transmission through cotton T-shirt fabrics with low
      ultraviolet protection by various laundering methods and dyeing: clinical
      implications.
AB  - BACKGROUND: The public has long been instructed to wear protective clothing
      against ultraviolet (UV) damage. OBJECTIVE: Our purpose was to determine the UV
      protection factor (UPF) of two cotton fabrics used in the manufacture of summer T
      shirts and to explore methods that could improve the UPF of these fabrics.
      METHODS: Each of the two types of white cotton fabrics (cotton T-shirt and
      mercerized cotton print cloth) used in this study was divided into 4 treatment
      groups: (1) water-only (machine washed with water), (2) detergent-only (washed
      with detergent), (3) detergent-UV absorber (washed with detergent and a UV
      absorber), and (4) dyes (dyed fabrics). Ultraviolet transmission through the
      fabrics was measured with a spectrophotometer before and after laundry and dyeing
      treatments. Based on UV transmission through these fabrics, the UPF values were
      calculated. RESULTS: Before any treatments, the mean UPFs were 4.94 for the T
      shirt fabric and 3.13 for the print cloth. There was greater UVA (320-400 nm)
      than UVB (280-320 nm) transmission through these fabrics. After 5 washings with
      water alone and with detergent alone, UPF increased by 51% and 17%, respectively,
      for the cotton T-shirt fabric. Washing the T-shirt fabrics with detergent plus
      the UV-absorbing agent increased the UPF by 407% after 5 treatments. Dyeing the
      fabric blue or yellow increased the UPF by 544% and 212%, respectively. Similar
      changes in UPFs were observed for the print cloth fabric. CONCLUSION: The two
      cotton fabrics used in this study offered limited protection against UV radiation
      as determined by spectrophotometric analysis. Laundering with detergent and water
      improves UPF slightly by causing fabric shrinkage. Dyeing fabrics or adding a UV
      absorbing agent during laundering substantially reduces UV transmission and
      increases UPF. More UVA is transmitted through the fabrics than UVB.

PMID- 11312423
TI  - Tanning salon exposure and molecular alterations.
AB  - BACKGROUND: Human studies of the short-term cellular effects of tanning salon
      exposures are lacking. Findings of such studies may prove extremely helpful in
      educating consumers considering or currently attending tanning salons. OBJECTIVE:
      Our purpose was to determine whether tanning salon exposure causes DNA
      alterations and p53 protein expression in epidermal keratinocytes and/or
      circulating peripheral lymphocytes. METHODS: Eleven subjects received 10 full
      body tanning salon exposures over a 2-week period. UV-induced DNA cyclobutane
      pyrimidine dimers and p53 protein expression were examined, comparing
      pretreatment peripheral blood lymphocytes and epidermal biopsy specimens with
      analogous specimens obtained after the 10 tanning salon exposures. RESULTS:
      Cyclobutane pyrimidine dimers in DNA and p53 protein expression were detected in
      epidermal keratinocytes, but were absent in lymphocytes. CONCLUSION: Similar to
      outdoor sun exposure, short-term recreational tanning salon exposure causes
      molecular alterations believed essential in the development of skin cancer.

PMID- 11312424
TI  - Mechanisms of sunscreen failure.
AB  - Sunscreen is used as a primary strategy to prevent sunburn and later skin cancer.
      However, sunscreen use has paradoxically been associated with the increasing
      incidence of skin cancer. One explanation for this puzzling observation is
      sunscreen failure (sunburn in the setting of sunscreen). Our purpose was to
      evaluate mechanisms of sunscreen failure in a sunscreen-using population. We
      carried out an epidemiologic comparison of sunburned and nonsunburned beachgoers
      who used sunscreen. We found that men were less likely to use sunscreen than
      women (chi(2) = 11.3, df = 1, P = .001), and when it was used, men were less
      likely to apply sunscreen to all sunlight-exposed skin (chi(2) = 18.4, df = 1, P
      = .0001). Swimmers who used sunscreen were significantly more likely to be
      sunburned compared with nonswimming sunscreen users (Fisher exact test, df = 1).
      Sunscreen may fail to prevent sunburn if it is washed off during swimming or if
      it is not applied to all exposed skin. Epidemiologic studies that link sunscreen
      use to skin cancer should evaluate whether sunburn occurred in this setting.

PMID- 11312425
TI  - Prevalence and predictors of skin disease in the Women's Interagency HIV Study
      (WIHS).
AB  - OBJECTIVE: We attempted to determine the prevalence and predictors of skin
      disease in a cohort of women with and at risk for HIV infection. METHODS: We
      analyzed baseline data from a multicenter longitudinal study of HIV infection in
      women. RESULTS: A total of 2018 HIV-infected women and 557 HIV-uninfected women
      were included in this analysis. Skin abnormalities were reported more frequently
      among HIV-infected than uninfected women (63% vs 44%, respectively; odds ratio
      [OR] 2.10; 95% confidence interval [95% CI], 1.74-2.54). Infected women were also
      more likely to have more than 2 skin diagnoses (OR, 3.27; 95% CI, 1.31-8.16).
      Folliculitis, seborrheic dermatitis, herpes zoster, and onychomycosis were more
      common among HIV-infected women (P < .05). Independent predictors of abnormal
      findings on skin examination in the infected women were African American race
      (OR, 1.38; 95% CI, 1.07-1.77), injection drug use (OR, 2.74; 95% CI, 2.11-3.57),
      CD4(+) count less than 50 (OR, 1.68; 95% CI, 1.17-2.42), and high viral loads
      (100,000-499,999 = OR, 1.77; 95% CI, 1.32-2.37; > 499,999 = OR, 2.15; 95% CI,
      1.42-3.27). CONCLUSION: HIV infection was associated with a greater number of
      skin abnormalities and with specific dermatologic diagnoses. Skin abnormalities
      were also more common among women with CD4(+) cell depletion or higher viral
      load.

PMID- 11312426
TI  - Acrochordons as a presenting sign of nevoid basal cell carcinoma syndrome.
AB  - BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a genodermatosis with
      autosomal dominant inheritance. In identified kindreds the diagnosis is
      relatively easy, but for the patients without family history of this syndrome a
      high clinical suspicion is necessary for diagnosis. OBJECTIVE: Acrochordons are
      distinctly uncommon in childhood. Our purpose was to evaluate skin tags that
      develop at an early age. METHODS: This is a retrospective series evaluation of 7
      children who presented with pedunculated papules (acrochordon-like growths). A
      full history was then correlated with biopsy results in each patient. RESULTS:
      Clinically, lesions consisted of flesh-colored and pigmented pedunculated
      papules. Histopathologic examination of these papules showed basal cell
      carcinomas in each biopsy specimen. CONCLUSION: We consider that "skin tag"-like
      basal cell carcinomas in childhood may represent a marker for NBCCS. Early
      diagnosis of this syndrome and early sun protection of the affected children
      could help decrease the number of lifetime tumors. Biopsy should be performed on
      acrochordons in children because they may be the presenting sign of NBCCS.
      Because these tags may precede other stigmata of the NBCCS, recognition may
      facilitate early diagnosis and allow early treatment and sun protection.

PMID- 11312427
TI  - Pruritus vulvae in prepubertal children.
AB  - BACKGROUND: Vulvar pruritus is a common complaint in females of all ages.
      However, little has been published on pruritus vulvae in children as a primary
      symptom. OBJECTIVE: Our purpose is to review the causes and treatments of vulvar
      pruritus in prepubertal girls and to retrospectively evaluate the causes and
      outcomes of the premenarchal children we studied. METHODS: The records of 44
      premenarchal girls with vulvar pruritus were reviewed, and follow-up interviews
      were performed by telephone. RESULTS: Thirty-three patients (75%) had nonspecific
      pruritus. Lichen sclerosus, bacterial infections, yeast infection, and pinworm
      infestation were seen in a minority of patients. At follow-up, pruritus had
      cleared in 15 patients, been alleviated in 13, and remained the same in 4.
      CONCLUSION: Most of our patients had nonspecific pruritus, which was alleviated
      by or cleared with better hygiene and avoidance of irritants. In prepubertal
      girls, poor hygiene and irritants such as soap are major contributors to pruritus
      vulvae. All patients may benefit from following hygienic measures and irritant
      precautions in addition to specific therapy directed at underlying causes.

PMID- 11312428
TI  - Childhood vulvar lichen sclerosus: an increasingly common problem.
AB  - BACKGROUND: Lichen sclerosus (LS) of the vulva in children is presenting more
      commonly, but its origin is unknown. OBJECTIVE: The purpose of this study was to
      assess the prevalence of childhood vulvar LS, to examine factors that may play a
      role in its cause, and to attempt to define the current optimal treatment.
      METHODS: We surveyed 70 cases of LS currently being treated in the pediatric
      vulvar clinic to collect information on presentation, family history, associated
      disease, and typical course of the disorder. We looked retrospectively and
      prospectively at treatments for LS. RESULTS: We found a prevalence of
      premenarchal LS of 1 in 900 and confirmed an increasing incidence. In a high
      proportion of cases (77%), the question of sexual abuse had been raised. A family
      history of LS was found in a minimum of 17% of cases. Associated autoimmune
      disease occurred in 14%, but 64% told of a family history, and atopy occurred in
      59%. Potent topical steroid ointments appear to alleviate symptoms most
      effectively, with minimal side effects. CONCLUSION: Although the cause of LS
      remains uncertain, it is not a rare disease in prepubertal girls. Current optimal
      management includes prompt diagnosis and institution of treatment with a potent
      topical steroid.

PMID- 11312429
TI  - Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results
      of a multicenter 6-week dose-response trial.
AB  - BACKGROUND: Superficial basal cell carcinoma (sBCC) is an increasingly common
      tumor in fair-skinned populations throughout the world. Imiquimod, an immune
      response modifier that induces cytokines including interferons, has been shown in
      preliminary studies to have an effect when applied topically to BCC. OBJECTIVE:
      We conducted a multicenter, randomized, open-label dose-response trial of
      imiquimod 5% cream in the treatment of primary sBCC assessing efficacy and safety
      of different dose regimens. METHODS: Ninety-nine patients were randomized to 6
      weeks' application of imiquimod in 1 of 4 treatment regimens: twice every day,
      once every day, twice daily 3 times/week, once daily 3 times/week. The treatment
      site was excised and examined histologically 6 weeks after cessation of
      imiquimod. RESULTS: Intention-to-treat analysis revealed 100% (3/3) histologic
      clearance in the twice-daily regimen, 87.9% (29/33) clearance in the once every
      day regimen, 73.3% (22/30) clearance in the twice-daily 3 times/week regimen, and
      69.7% (23/33) clearance in the once-daily 3 times/week regimen. Dose-related
      inflammatory skin reactions at the site of application were common. The majority
      were well tolerated and only 1 patient withdrew from the trial as a result of a
      medication-related skin reaction. CONCLUSION: Imiquimod 5% cream appears to have
      potential as a patient-administered treatment option in sBCC.

PMID- 11312431
TI  - Emerging treatment for epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare, chronic, subepidermal,
      mucocutaneous blistering disease characterized by skin fragility and spontaneous
      as well as trauma-induced blisters that heal with scar formation and milia.
      Treatment is often frustrating because conventional therapy with corticosteroids
      and immunosuppressive agents frequently does not result in significant clinical
      improvement. We review the conventional treatment of EBA and critically analyze
      the literature on various adjuvants and therapeutic modalities that have recently
      been used. These include cyclosporine, colchicine, plasmapheresis, extracorporeal
      photochemotherapy, and intravenous gammaglobulins. Although the data are
      preliminary, they suggest that intravenous immunoglobulins may be a promising
      treatment modality for resistant, nonresponsive, or refractory EBA. The use of
      intravenous immunoglobulins results in significant improvement of skin and
      mucosal lesions, and it is quite safe, with minimal side effects.

PMID- 11312430
TI  - Oral dexamethasone pulse treatment for vitiligo.
AB  - BACKGROUND: Oral corticosteroid pulse therapy has provided inconsistent results
      in the treatment of Indian patients with vitiligo. OBJECTIVE: We wanted to
      evaluate the efficacy, safety, and tolerability of oral dexamethasone pulse
      therapy in a cohort of Austrian patients with vitiligo. METHODS: Twenty-nine
      patients with vitiligo were included in the study. Of these, 25 had progressive
      and 4 had stable disease. The patients were given weekly pulses of 10 mg
      dexamethasone each on 2 consecutive days followed by 5 days off treatment for a
      maximum period of 24 weeks. Clinical response and side effects were evaluated in
      monthly intervals. Plasma cortisol and corticotropin levels were monitored before
      and up to 6 days after the dexamethasone pulse in the first and fourth week of
      treatment in 14 patients. RESULTS: After a mean treatment period of 18.2 +/- 5.2
      weeks, the disease activity was arrested in 22 of 25 patients (88%) who had
      active vitiligo before the study. Marked repigmentation occurred in 2 patients
      (6.9%) and moderate or slight repigmentation in 3 patients (10.3%) each. No
      response was noted in 21 patients (72.4%). Side effects were recorded in 20
      patients (69%) and included weight gain, insomnia, acne, agitation, menstrual
      disturbance, and hypertrichosis. Plasma cortisol and corticotropin values were
      markedly decreased 24 hours after the second dexamethasone dose, yet returned to
      baseline values within the off treatment period before the next dexamethasone
      pulse. CONCLUSION: Our data show that oral dexamethasone pulse treatment is
      effective in arresting progression of vitiligo yet fails to induce satisfactory
      repigmentation in the great majority of our patient cohort. Mild to moderate side
      effects are common with this treatment modality; however, sustained suppression
      of endogenous cortisol production does not occur with the pulse regimen.

PMID- 11312432
TI  - Angiotropic malignant melanoma: a rare pattern of local metastases.
AB  - We report a case of angiotropic malignant melanoma and review previously reported
      cases. Vessel walls should be scanned for tumor cells in biopsy and re-excision
      specimens of melanoma.

PMID- 11312433
TI  - Rapid HMB-45 staining in Mohs micrographic surgery for melanoma in situ and
      invasive melanoma.
AB  - BACKGROUND: Accurate interpretation of frozen sections in the treatment of
      melanoma by Mohs micrographic surgery may be difficult. OBJECTIVE: Our purpose
      was to review the literature on the role of Mohs micrographic surgery in the
      treatment of melanoma and to demonstrate the added benefits of using rapid HMB-45
      staining in Mohs micrographic surgery for the treatment of melanoma. METHODS:
      Twenty cases of melanoma were included in our study. Histologic diagnosis in each
      case was made by means of excisional biopsy specimens and permanent sections.
      Mohs micrographic surgery was performed with 3-mm margins used for each stage.
      Each Mohs frozen section was stained with HMB-45. In addition, routine frozen
      sections stained with hematoxylin-eosin were also prepared for comparison. All
      tissues were also sent for permanent sections. These permanent sections were cut
      similarly to Mohs-oriented sections because they were sectioned horizontally.
      Since they were serving as the standard, no staining with HMB-45 was performed on
      these permanent sections. Further stages with 3-mm margins were taken until
      tissues stained negative. Frozen sections were compared with permanent sections
      at each stage of resection. RESULTS: Eleven of the 20 cases stained positive with
      HMB-45 antibody on the first Mohs stage. These results were consistent with
      findings on permanent sections. Ten of the 11 cases were cleared by the first
      stage. One of the 11 cases required 3 stages because margins were not cleared and
      the specimens stained HMB-45 positive. However, permanent sections in this case
      revealed no tumor in the second stage. Nine of 20 cases did not stain with HMB-45
      on the first layer of Mohs excision. This was consistent with findings on
      permanent sections. CONCLUSION: HMB-45 staining serves as a rapid technique to
      aid in the interpretation of frozen sections during Mohs micrographic surgery in
      the treatment of melanoma.

PMID- 11312434
TI  - Ultraviolet A and melanoma: a review.
AB  - The incidence and mortality rates of melanoma have risen for many decades in the
      United States. Increased exposure to ultraviolet (UV) radiation is generally
      considered to be responsible. Sunburns, a measure of excess sun exposure, have
      been identified as a risk factor for the development of melanoma. Because
      sunburns are primarily due to UVB (280-320 nm) radiation, UVB has been implicated
      as a potential contributing factor to the pathogenesis of melanoma. The adverse
      role of UVA (320-400 nm) in this regard is less well studied, and currently there
      is a great deal of controversy regarding the relationship between UVA exposure
      and the development of melanoma. This article reviews evidence in the English
      language literature that surrounds the controversy concerning a possible role for
      UVA in the origin of melanoma. Our search found that UVA causes DNA damage via
      photosensitized reactions that result in the production of oxygen radical
      species. UVA can induce mutations in various cultured cell lines. Furthermore, in
      two animal models, the hybrid Xiphophorus fish and the opossum (Mondelphis
      domestica), melanomas and melanoma precursors can be induced with UVA. UVA
      radiation has been reported to produce immunosuppression in laboratory animals
      and in humans. Some epidemiologic studies have reported an increase in melanomas
      in users of sunbeds and sunscreens and in patients exposed to psoralen and UVA
      (PUVA) therapy. There is basic scientific evidence of the harmful effects of UVA
      on DNA, cells and animals. Collectively, these data suggest a potential role for
      UVA in the pathogenesis of melanoma. To date evidence from epidemiologic studies
      and clinical observations are inconclusive but seem to be consistent with this
      hypothesis. Additional research on the possible role of UVA in the pathogenesis
      of melanoma is required.

PMID- 11312435
TI  - Advances in molecular medicine.

PMID- 11312436
TI  - Surgical pearl: composite film and graft unit for the recipient area dressing
      after split-thickness skin grafting in vitiligo.

PMID- 11312437
TI  - Skin and nail changes in children with sickle cell anemia receiving hydroxyurea
      therapy.
AB  - Skin and nail changes from long-term hydroxyurea therapy are reported in adults.
      Skin and nail changes, including nail hyperpigmentation, longitudinal bands, and
      hyperpigmentation of the palms and other skin surfaces, developed in 7 children
      with sickle cell anemia after 6 to 16 weeks of hydroxyurea therapy. Cutaneous and
      nail changes may occur in children receiving hydroxyurea.

PMID- 11312438
TI  - Sweet's syndrome and Chlamydia pneumoniae infection.
AB  - We report the case of a patient in whom Sweet's syndrome developed during
      pneumonia caused by Chlamydia pneumoniae. Increased expression of helper T-cell
      type 1 cytokine secretion pattern in peripheral blood has recently been observed
      in patients with this syndrome, and chlamydia infection is known to primarily
      activate a helper T-cell type 1 immunologic response.

PMID- 11312439
TI  - Penile dermatophytosis.
AB  - Dermatophyte infections of the penis and scrotum are relatively rare compared
      with those involving the groin. Four cases of penile tinea due to Trichophyton
      rubrum are described. All patients had associated foci of fungal infection, but
      only one had crural involvement. Treatment with oral antifungal agents led to
      complete resolution of penile dermatophytosis.

PMID- 11312440
TI  - Beard dermatitis due to para-phenylenediamine use in Arabic men.
AB  - The most common active ingredient in hair coloring is para-phenylenediamine
      (PPDA), which can produce contact dermatitis, particularly in persons who dye
      their scalp hair and in hairdressers. We have identified another group of
      patients also at risk, namely men from Arab countries, who commonly grow beards
      and dye them. We searched the computerized patient database at the Mayo Clinic
      for patients with beard dermatitis associated with dye use. Eight Arabic men
      presented to the Mayo Clinic between 1994 and 1999 with beard dermatitis and a
      positive patch test to PPDA. The lesions were described as pruritic,
      erythematous, papular eruptions that developed in the jaw area after each
      application of beard dye. The symptoms subsided after the patients discontinued
      use of the PPDA-containing dye and received treatment with topical
      corticosteroids. Allergic contact dermatitis in the beard area due to PPDA occurs
      in Arabic men as a result of their propensity to dye their beards.

PMID- 11312441
TI  - Angiotropic malignant melanoma: more common than we think?

PMID- 11312442
TI  - Blue in the face.

PMID- 11312444
TI  - Rest azured?

PMID- 11312445
TI  - Subungual melanoma obscured by nail polish.

PMID- 11312446
TI  - Muckle-Wells syndrome?

PMID- 11312448
TI  - Sentinel lymph node mapping and biopsy in the evaluation of primary melanoma.

PMID- 11312450
TI  - Acne rosacea occurring after carbon dioxide laser treatment.

PMID- 11312451
TI  - Incidence of penile lichen sclerosus.

PMID- 11312454
TI  - The Surgeon General's Report on Oral Health: defining priorities.

PMID- 11312452
TI  - Liver biopsies and methotrexate: a time for reconsideration?

PMID- 11312455
TI  - Gap versus interposition arthroplasty for ankylosis of the temporomandibular
      joint.

PMID- 11312456
TI  - Treating chronic diffuse sclerosing osteomyelitis of the mandible with
      saucerization and autogenous bone grafting.
AB  - OBJECTIVE: Chronic diffuse sclerosing osteomyelitis of the mandible is a
      difficult-to-treat disease characterized by recurrent symptoms. The purpose of
      this study was to determine the results of particulate cancellous bone and marrow
      grafting after saucerization in the surgical treatment of diffuse sclerosing
      osteomyelitis of the mandible. STUDY DESIGN: Six patients with chronic diffuse
      sclerosing osteomyelitis of the mandible were treated by particulate cancellous
      bone and marrow grafting after saucerization and were retrospectively evaluated.
      Treatment results were evaluated with repeated comprehensive clinical
      investigation and radiologic/scintigraphic analysis. RESULTS: After the surgical
      procedure, all patients indicated maintenance of mandible continuity, contour,
      and function. Furthermore, 3 patients were symptom-free and the remaining 3
      patients exhibited improvement. CONCLUSIONS: The partial resection of the
      mandible is associated with disadvantages, including loss of mandibular support,
      dysfunction, and problems related to mandibular reconstruction. Therefore, it
      would be reasonable to choose saucerization combined with particulate cancellous
      bone and marrow grafting, which is a relatively conservative surgical treatment
      for chronic diffuse sclerosing osteomyelitis of the mandible.

PMID- 11312457
TI  - Lingual flap retraction and prevention of lingual nerve damage associated with
      third molar surgery: a systematic review of the literature.
AB  - OBJECTIVE: Lingual nerve damage sometimes occurs after the removal of third
      molars. The use of a lingual retractor has been advocated to protect the lingual
      nerve. A systematic review of the literature was undertaken to evaluate the
      incidence of lingual nerve damage after third molar surgery and the effect of a
      lingual retractor on nerve damage. STUDY DESIGN: An exhaustive computerized
      search of several databases and references cited in the various studies was
      performed. Predetermined inclusion and exclusion criteria were used to identify
      the 8 published studies acceptable for detailed analysis. The incidence and
      spontaneous recovery of lingual nerve injury for the following 3 surgical
      techniques were evaluated: the buccal approach with lingual flap retraction
      (BA+), or the buccal approach without lingual flap retraction (BA-), and the
      lingual split technique with lingual flap retraction (LS). RESULTS: In the 8
      selected articles, lingual nerve injury occurred in 9.6%, 6.4%, and 0.6% of the
      pooled LS, BA+, and BA- procedures, respectively. On the basis of risk ratios
      comparing combined incidence rates, lingual nerve injury is 8.8 times more likely
      to occur in BA+ than in BA- procedures (CI = 4.3-17.8), 13.3 times more likely to
      occur in LS than in BA- procedures (CI = 6.6-26.9), and 1.5 times more likely to
      occur in LS than in BA+ procedures (CI = 1.2-1.8). Permanent lingual nerve injury
      occurred in 0.1%, 0.6%, and 0.2% of the combined LS, BA+, and BA- procedures,
      respectively. The combined permanent incidence risk ratios were not calculated
      because of the low permanent incidence rates. CONCLUSIONS: The use of a lingual
      nerve retractor during third molar surgery was associated with an increased
      incidence of temporary nerve damage and was neither protective nor detrimental
      with respect to the incidence of permanent nerve damage.

PMID- 11312458
TI  - The incremental challenge test in the diagnosis of adverse reactions to local
      anesthetics.
AB  - OBJECTIVE: The aim of this study was to assess the reliability of a diagnostic
      protocol, the incremental challenge test (ICT), for patients with and without a
      history of adverse reactions to local anesthetics (LAs) or other drugs, to select
      an LA that could be safely used. STUDY DESIGN: The ICT was performed on 432
      subjects, 314 female and 118 male. Four hundred thirty-two challenges were
      carried out with LAs that were free of adrenaline and preservatives. Chi-square
      analysis was performed to evaluate the existence of different predispositions to
      ICT positivity among subjects of the 4 categories studied. RESULTS: Four hundred
      fifteen tests were completed with no clinical events occurring. The analysis did
      not show any significant difference (chi-square = 6.17; P >.05). CONCLUSIONS: Our
      results confirm that immunoglobulin E-mediated reactions to LAs are uncommon and
      that the ICT offers safety and specificity in diagnosing adverse reactions to
      LAs, allowing for the selection of a safe and reliable LA.

PMID- 11312459
TI  - Anesthetic efficacy of ropivacaine in maxillary anterior infiltration.
AB  - OBJECTIVE: The purpose of this prospective, randomized double-blind study was to
      evaluate and compare the anesthetic efficacy of 0.5% ropivacaine with 1:200,000
      epinephrine, of 0.5% ropivacaine, and of 0.5% bupivacaine with 1:200,000
      epinephrine in maxillary lateral incisor infiltrations. STUDY DESIGN: Forty
      subjects randomly received, in a double-blind manner, 3 infiltrations at 3
      separate appointments, in a repeated-measures design. The injections consisted of
      an infiltration of 1.8 mL of 0.5% ropivacaine plain, an infiltration of 1.8 mL of
      0.5% ropivacaine with 1:200,000 epinephrine, and an infiltration of 1.8 mL of
      0.5% bupivacaine with 1:200,000 epinephrine (control solution). The maxillary
      lateral incisor pulpal anesthesia was evaluated with an electric pulp tester at 2
      minute cycles for 90 minutes after injection. No response from the subject to the
      maximum output (80 reading) of the pulp tester was used as the criterion for
      pulpal anesthesia. Anesthesia was considered successful when 2 consecutive 80
      readings were obtained. The duration of pulpal anesthesia was recorded as the
      last 80 reading. RESULTS: One hundred percent of the subjects had lip numbness
      with all solutions. The anesthetic success rates for ropivacaine plain,
      ropivacaine with epinephrine, and bupivacaine with epinephrine were 68%, 75%, and
      80%, respectively. There were no significant differences (P >.05) among the
      solutions. The duration of pulpal anesthesia (80 readings) for ropivacaine plain,
      ropivacaine with epinephrine, and bupivacaine with epinephrine was 13 minutes, 33
      minutes, and 33 minutes, respectively. Ropivacaine plain had a significantly
      shorter duration of pulpal anesthesia than ropivacaine with epinephrine.
      CONCLUSIONS: We concluded that 0.5% ropivacaine with 1:200,000 epinephrine was
      equivalent to 0.5% bupivacaine with 1:200,000 epinephrine in pharmacologic
      action. The duration of pulpal anesthesia was less for ropivacaine without
      epinephrine. Ropivacaine with epinephrine has the potential to replace
      bupivacaine with epinephrine in clinical dental practice because of the decreased
      potential for cardiac and central nervous system toxicity.

PMID- 11312460
TI  - Gigantiform cementoma: clinicopathologic presentation of 3 cases.
AB  - Gigantiform cementoma is a rare, benign fibro-cemento-osseous disease of the
      jaws, seen most frequently in young girls. Radiographically, it typically
      presents as multiquadrant, expansile, mixed radiolucent-opaque lesions that cross
      the midlines of the jaws. Although cases with a familial pattern are noted in a
      few publications, sporadic cases have been reported without a family history. The
      term gigantiform cementoma has been used interchangeably with designations of
      other fibro-osseous entities, yet its application should be restricted by the
      criteria defined herein. In this article, we report 3 cases of gigantiform
      cementoma. Clinical, radiographic, and microscopic features of these lesions are
      presented, along with criteria to differentiate gigantiform cementoma from other
      fibro-osseous diseases of the jaws. A possible pathogenetic mechanism and
      treatment recommendations are discussed.

PMID- 11312461
TI  - Osteosarcoma of the jaw. The Chaim Sheba Medical Center experience.
AB  - OBJECTIVE: The purpose of this article is to present 14 cases of osteosarcoma of
      the jaw treated at our medical center from 1989 to 1998. These cases are
      discussed in the light of a comprehensive review of 774 cases reported in the
      English literature over the past 3 decades. Differences between osteosarcoma of
      the jaws and osteosarcoma of the long bones are examined. SUBJECTS AND METHODS:
      The patients ranged in age from 8 to 78 years, the mean age being 33 years. Each
      patient had a histopathologically established diagnosis of osteosarcoma of the
      jaw. Records were reviewed for epidemiologic data, treatment modalities, and
      survival. RESULTS: Of the 14 patients, 6 (42%) had tumors in the mandible and 8
      (58%) had tumors in the maxilla. Of the mandibular tumors, 5 occurred in the body
      of the mandible; all maxillary tumors originated in the alveolar ridge and
      involved the maxillary sinus. The chief complaint was an intraoral or extraoral
      painless swelling. Histopathologic types included chondroblastic, osteoblastic,
      fibroblastic, and malignant fibrous histiocytoma-like. Pathologic grade was
      determined to be high (3 or 4) in 13 cases and low (1) in only 1 mandibular case.
      All patients underwent surgical resection and immediate reconstruction. Adjuvant
      therapy included postoperative radiation (5 patients), postoperative chemotherapy
      (2 patients), and preoperative chemotherapy and postoperative radiation (1
      patient). CONCLUSIONS: The results of the present study support the literature
      indicating that osteosarcoma of the jaw differs from osteosarcoma of the long
      bones in its biological behavior even though they have the same histologic
      appearance. Because of differences in tumor characteristics, the introduction of
      chemotherapy did not dramatically alter the prognosis of osteosarcoma of the jaw.
      Early diagnosis and radical surgery are the keys to high survival rates.

PMID- 11312462
TI  - Osteosarcoma metastatic to the mandible: a case report.
AB  - A case of osteosarcoma that metastasized to the mandibular ramus from the femur
      in a 36-year-old man is presented. The patient was referred to us for the
      diagnosis and treatment of swelling of the left cheek. Radiologic examination
      showed a radiolucent lesion containing radiopaque areas within the left
      mandibular ramus. The patient previously suffered from a femoral small cell
      osteosarcoma, which was resected 71 months before our first examination. After
      induction of general anesthesia, a unilateral mandibulectomy and a simultaneous
      reconstruction using a titanium plate and an artificial condyle were performed.
      The postoperative course was uneventful, with satisfactory facial appearance and
      jaw function. The histopathologic features of the mandibular tumor were identical
      to those of the femoral tumor. Thus the mandibular lesion was diagnosed as a
      metastatic small cell osteosarcoma. At 27 months after the operation there had
      been no recurrence.

PMID- 11312463
TI  - Metachronous bilateral primary adenocarcinoma of the submandibular glands.
AB  - A young woman developed an unusual adenocarcinoma in each submandibular salivary
      gland at an interval of 30 months. This presentation has not been described
      previously. The possible etiology for this and treatment options are discussed.
      The choice of diagnostic imaging (ultrasound versus magnetic resonance imaging)
      is highlighted. As a result of regular follow-ups using diagnostic ultrasound, a
      second tumor was observed to reach a dimension of 8 mm in less than 6 months.
      This is probably the first report documenting the extent of initial growth of
      this rare tumor.

PMID- 11312464
TI  - An in vitro experiment on the effect of an attempt to create an apical matrix
      during root canal preparation on coronal leakage and material extrusion.
AB  - OBJECTIVE: A common approach to creating an apical matrix (apical stop) in the
      apical dentin is to enlarge the root canal to 3 sizes greater than that of the
      first file that binds at the working length. The aim of this study was to test
      the hypothesis that this procedure will reduce the amount of material extruded
      and the leakage along the apical root fillings. STUDY DESIGN: The canals of half
      of 120 maxillary and mandibular canines were prepared to the apical foramen
      through use of the serial shaping technique; the apical matrix creation procedure
      was not used. Each of the other 60 canals was prepared to 1 mm short of the
      apical foramen, and the canal was enlarged to at least 3 sizes greater than that
      of the first binding file to create an apical matrix. All the canals prepared
      with and all the canals prepared without the apical matrix creation procedure
      were obturated with laterally or vertically compacted cold or warm gutta-percha.
      In the leakage test, after post space preparation, the amount of fluid transport
      along the apical root fillings was measured. In the material extrusion test, the
      number of teeth with gutta-percha extrusion was recorded and the weight of the
      apically extruded materials was measured. RESULTS: In both the leakage and the
      extrusion tests, no significant difference was found between canals prepared with
      and canals prepared without the apical matrix creation procedure. CONCLUSION: The
      hypothesis that a procedure to enlarge root canals to 3 sizes greater than that
      of the first binding file will reduce the amount of filling materials extruded
      and the leakage was not proved, as our results show.

PMID- 11312465
TI  - "Red complex" (Bacteroides forsythus, Porphyromonas gingivalis, and Treponema
      denticola) in endodontic infections: a molecular approach.
AB  - OBJECTIVE: The "red complex," composed of Bacteroides forsythus, Porphyromonas
      gingivalis, and Treponema denticola, is implicated in severe forms of periodontal
      diseases. The purpose of this study was to assess the occurrence of the red
      complex in root canal infections through the use of a sensitive technique-the 16S
      rDNA-directed polymerase chain reaction (PCR). STUDY DESIGN: Samples were
      obtained from 50 necrotic pulps with periradicular pathosis. Ten cases were
      diagnosed as acute periradicular abscesses. DNA was extracted from the samples
      and analyzed with a PCR-based identification assay. RESULTS: At least 1 member of
      the red complex was found in 33 of 50 cases. T denticola, P gingivalis, and B
      forsythus were detected in 44%, 30%, and 26% of the cases, respectively. The red
      complex was found in 4 of 50 cases. No particular signs or symptoms were
      associated with the presence of these bacterial species. CONCLUSIONS: Despite
      what is indicated in reports with respect to marginal periodontitis, red complex
      bacteria-either singularly or collectively-was not associated with any particular
      pattern of clinical symptoms. However, because the bacterial species from the red
      complex are recognized oral pathogens, their occurrence in root canal infections
      suggests that they may play a role in the pathogenesis of periradicular diseases.

PMID- 11312466
TI  - Blood flow in and around the masseter muscle: normal and pathologic features
      demonstrated by color Doppler sonography.
AB  - OBJECTIVE: The purpose of this study was to clarify the normal findings of
      arteries in and around the masseter muscle and to present their pathologic
      changes with the use of color Doppler sonography. STUDY DESIGN: The vascular
      appearances were examined for the 4 main arteries feeding the masseter muscle in
      healthy volunteers (n = 38) and patients with inflammation (n = 5) and
      intramuscular hemangioma (n = 3). The features of these arteries were
      investigated together with the flow diameter, flow velocities, and arterial
      resistances. The symmetry indices were also calculated to assess the pathologic
      changes. RESULTS: The detection rates of the branch from the transverse facial
      artery, the masseter artery, and the branch from the maxillary or external
      carotid artery were 98.7%, 21.1%, and 84.2% in healthy volunteers, respectively.
      The facial artery that feeds the muscle from the inferior part represented 2
      patterns according to anatomic variant: the masseteric branch (22.4%) and the
      main trunk itself (77.6%). The means of the flow diameter, maximum and minimum
      velocities, resistive index, and pulsatility index in healthy subjects were 1.8
      mm, 24.6 cm/s, 5.1 cm/s, 0.80, and 2.51, respectively. In most of the patients
      with symptoms, the symmetry indices of all measurement values increased in
      comparison with those of healthy volunteers. CONCLUSION: Color Doppler sonography
      is useful in describing the arteries in and around the masseter muscle and has
      the potential of being used to depict the pathologic changes.

PMID- 11312467
TI  - Foreign-body granuloma occurring in the mandible subsequent to orthognathic
      surgery: a case report.
AB  - We report the first case of foreign-body granuloma occurring in the mandible of a
      patient with a history of orthognathic surgery. A 20-year-old male patient had a
      hard swelling and pain in the left mandibular angle and the parotid area. Plain
      radiographs showed a radiolucent lesion extending from the buccal area under the
      left sigmoid notch of the mandible to the mandibular angle. Computed tomographs
      showed an expanded osteolytic mass in the same area, with destruction of most of
      the bone on the buccal side. A microscopic examination revealed filamentous
      foreign material associated with chronic inflammatory cell infiltration and an
      aggregation of multinucleated giant cells. Foreign-body granuloma in the
      mandible, although rare, should be included in the differential diagnosis in
      cases of postoperative masses.

PMID- 11312468
TI  - Alveolar process fractal dimension and postcranial bone density.
AB  - OBJECTIVES: Our goal was to determine whether the radiographic fractal dimension
      of the maxillary and mandibular alveolar processes is related to bone density of
      the alveolar processes, spine, hip, and radius in healthy women. STUDY DESIGN:
      Thirty-seven dentate healthy white women aged 20 to 78 years underwent assessment
      of systemic and alveolar process bone. After a periodontal examination, D-speed
      vertical bite-wing and periapical radiographs with aluminum step wedges and a
      density correction algorithm were used to make alveolar process fractal dimension
      and density calculations within regions of interest that avoided crestal bone and
      intrabony defects. Anteroposterior (L1-L4) and lateral (L2-L4) lumbar spine,
      total hip, and total wrist densities were determined by means of dual energy x
      ray absorptiometry. RESULTS: Correlation analysis revealed significant
      relationships between maxillary alveolar process fractal dimension and maxillary
      alveolar process density (r = 0.47, P < or =.01), mandibular alveolar process
      density (r = 0.48, P < or =.01), and mandibular alveolar process fractal
      dimension (r = 0.44, P < or =.05); and between mandibular alveolar process
      fractal dimension and maxillary alveolar process density (r = 0.54, P < or =.01)
      and mandibular alveolar process density (r = 0.58, P < or =.001). No significant
      relationships were found between the maxillary alveolar process or the mandibular
      alveolar process fractal dimension and the density of any postcranial regions.
      CONCLUSIONS: In healthy women, the alveolar process radiographic fractal
      dimension is significantly related to the alveolar process density but is not
      related to the density of the spine, hip, or radius.

PMID- 11312469
TI  - Online and enhanced.

PMID- 11312470
TI  - Effect of gender on fast-track recovery after coronary artery bypass graft
      surgery.
AB  - OBJECTIVE: To examine the effects of gender on time to extubation after coronary
      artery bypass graft (CABG) surgery and intensive care unit and hospital length of
      stay. DESIGN: Retrospective study comparing outcomes as related to gender.
      SETTING: Tertiary care university teaching hospital. PARTICIPANTS: Consecutive
      patients (n = 561; 376 men, 185 women) undergoing CABG surgery between January
      1995 and December 1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Early
      extubation was possible in 74% of men versus 64% of women (p = 0.03); length of
      stay was < or =5 days in 60% of men versus 48% of women (p = 0.008); overall
      postoperative length of stay was 5.7 days for men versus 6.5 days for women (p =
      0.003); morbidity and mortality were not significantly different between groups.
      CONCLUSION: Women undergoing CABG surgery with a standardized fast-track protocol
      have longer intubation times, intensive care unit length of stay, and hospital
      length of stay than their male counterparts.

PMID- 11312471
TI  - Ultra-fast-track anesthetic technique facilitates operating room extubation in
      patients undergoing off-pump coronary revascularization surgery.
AB  - OBJECTIVE: To determine if implementation of ultra-fast-track anesthetic (UFTA)
      technique facilitates operating room extubation in patients undergoing off-pump
      coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective review.
      SETTING: Referral center for cardiovascular surgery at a university hospital.
      PARTICIPANTS: Thirty-seven patients undergoing off-pump CABG surgery.
      INTERVENTIONS: Two groups represented UFTA (n = 10) and standard anesthetic
      (controls, n = 27) techniques. Anesthesia was conducted with propofol,
      remifentanil, vecuronium, and thoracic epidural analgesia in the UFTA group and
      thiopental, fentanyl, pancuronium, and isoflurane in the control group. Active
      temperature control was an integral part of the UFTA technique but not the
      standard technique. The active temperature control included intravenous fluid
      warmer, prewarmed skin preparation, humidified inspired gases, a circulating
      water warming blanket, and a forced-air warmer, along with the maintenance of the
      operating room temperature at 24 degrees C. The control group was managed with an
      intravenous fluid warmer, and the ambient temperature remained constant (20
      degrees C). Patients who did not satisfy extubation criteria within 30 minutes
      from the end of surgery were sedated and transferred to the intensive care unit
      (ICU). MEASUREMENTS AND MAIN RESULTS: All patients in the UFTA group and 2 in the
      control group were extubated in the operating room immediately after surgery.
      None of the patients required reintubation. There was no significant difference
      in postextubation PaO(2) and PaCO(2) between the groups. Nasopharyngeal
      temperature decreased from 36.7 +/- 0.4 degrees C to 36.4 +/- 0.3 degrees C in
      the UFTA group and from 36.6 +/- 0.5 degrees C to 35.6 +/- 0.4 degrees C in the
      control group (p < 0.0001). Bradycardia occurred significantly more often in the
      UFTA group but there was no difference in episodes of hypotension. There were no
      perioperative deaths. Patients who were extubated in the operating room required
      lower nurse-to-patient acuity ratio (1:2) in the ICU. No difference was found in
      ICU and hospital length of stay. CONCLUSIONS: Implementation of UFTA technique
      provided adequate hemodynamic control and facilitated operating room extubation
      in all patients. The impact of UFTA on earlier patient discharge and actual cost
      savings within a fully integrated post-cardiac surgery unit requires further
      evaluation.

PMID- 11312472
TI  - A survey of spinal and epidural techniques in adult cardiac surgery.
AB  - OBJECTIVE: To determine if a significant number of anesthesiologists are
      performing spinal and epidural techniques in adults undergoing cardiac surgery
      and if any neurologic injuries have been associated with these techniques.
      DESIGN: Anonymous survey of clinical practice. SETTING: Data collected via mail
      from members of the Society of Cardiovascular Anesthesiologists. PARTICIPANTS:
      Attending anesthesiologists. INTERVENTIONS: Anesthesiologists completed an
      anonymous survey of their use of spinal and epidural techniques in adult patients
      undergoing cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Of 3974
      anesthesiologists, 974 (24%) responded to the questionnaire; 892 are at
      institutions that perform cardiac surgery. Of the 892 responders, 68 (7.6%)
      reported they use spinal techniques, whereas 62 (7%) reported they use epidural
      techniques. Nine (1%) anesthesiologists reported they use both techniques. There
      were no reports of neurologic complications related to the use of spinal or
      epidural techniques performed by the anesthesiologists responding to the survey.
      CONCLUSIONS: A significant number of anesthesiologists are performing spinal and
      epidural techniques in adult patients undergoing cardiac surgery. Prospective,
      controlled trials should be performed to evaluate the benefits and risks of
      spinal and epidural techniques in this population.

PMID- 11312473
TI  - Vital capacity inhalation induction with sevoflurane: an alternative to standard
      intravenous induction for patients undergoing cardiac surgery.
AB  - OBJECTIVE: To determine the respiratory and cardiovascular effects of a high
      concentration vital capacity induction with sevoflurane compared with an
      intravenous induction with etomidate in patients scheduled for elective coronary
      artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized, double
      blind, controlled clinical trial. SETTING: Cardiothoracic unit at a university
      hospital referral center. PARTICIPANTS: Twenty-two patients undergoing elective
      CABG surgery. INTERVENTIONS: The study group (group S) received a vital capacity
      gaseous induction with sevoflurane 8% (n = 12) and the control group (group E)
      were given etomidate, 0.2 to 0.3 mg/kg (n = 10). Anesthesia was supplemented with
      fentanyl, 8 microg/kg, and vecuronium, 0.1 mg/kg, in both groups. MEASUREMENTS
      AND MAIN RESULTS: The speed of induction of anesthesia was comparable between the
      groups. There was a significant increase in minute ventilation after induction of
      anesthesia in both groups. This increase was associated with a small reduction in
      PaCO2. There were no clinically significant changes in pH and PaO(2). The
      incidence of breath-holding and the need for an oropharyngeal airway were similar
      between the groups. Both groups had similar reductions in mean arterial pressure
      and cardiac output during the study period; however, a downward trend in mean
      pulmonary artery pressure was noted in group S, whereas in group E it remained
      unchanged. Absolute plasma epinephrine and norepinephrine values were low during
      the precardiopulmonary bypass period in both groups. CONCLUSIONS: The technique
      of vital capacity inhalation induction with 8% sevoflurane offers a rapid onset
      of anesthesia, satisfactory airway control, and a good hemodynamic profile.
      Consideration should be given to the benefits of single-agent anesthesia and
      lowered pulmonary artery pressure during the precardiopulmonary bypass period. In
      addition to CABG surgery, this technique could be considered in patients with
      coronary artery disease undergoing noncardiac surgery, particularly for
      procedures in which spontaneous ventilation is preferred.

PMID- 11312474
TI  - Sevoflurane versus isoflurane in patients undergoing valvular cardiac surgery.
AB  - OBJECTIVE: To determine if sevoflurane provides hemodynamic and recovery
      characteristics comparable to isoflurane in patients undergoing surgery for
      valvular heart disease. DESIGN: A prospective crossover, dose-response study
      using sevoflurane and isoflurane before the start of surgery, followed by
      randomization to sevoflurane or isoflurane for surgery with blinded assessment
      for recovery. SETTING: Tertiary referral cardiac center. PARTICIPANTS: Twenty
      seven patients scheduled for elective valve surgery. Surgery consisted of 18
      aortic valve and 12 mitral valve replacements, of which 3 patients had 2 valves
      replaced; 1, tricuspid repair; and 8, coronary artery bypass procedures.
      INTERVENTIONS: A pulmonary artery catheter was used to obtain a complete
      hemodynamic profile during the dose-response study before surgery.
      Transesophageal echocardiography was used to confirm the diagnosis, and
      electrocardiography monitored for myocardial ischemia. MEASUREMENTS AND MAIN
      RESULTS: Both agents showed similar hemodynamic effects at 0.5 and 1.0 minimum
      alveolar concentration. There was a tendency to decreases in heart rate, blood
      pressure, and cardiac output, whereas filling pressures remained stable with each
      volatile agent. Electrocardiography did not detect ischemic changes. Times to eye
      opening and extubation were similar with both agents, with sevoflurane tending to
      be earlier than isoflurane. CONCLUSION: Sevoflurane showed a tendency to lower
      heart rates and cardiac index compared with isoflurane. Eye opening and
      extubation were slightly earlier. These findings were not statistically
      significant, however.

PMID- 11312475
TI  - Desflurane pharmacokinetics during cardiopulmonary bypass.
AB  - OBJECTIVE: To describe the washin and washout of desflurane when first
      administered during cardiopulmonary bypass (CPB) for cardiac surgery. DESIGN: A
      single-arm prospective study. SETTING: University-affiliated hospital operating
      room. PARTICIPANTS: Ten adult patients presenting for cardiac surgery.
      INTERVENTIONS: Consenting patients presenting for cardiac surgery received
      anesthesia with midazolam and fentanyl. Patients were cooled to 32 degrees C on
      CPB, then desflurane 6% was administered and blood samples drawn repeatedly from
      the arterial and venous bypass cannulae as well as from the membrane oxygenator
      inlet and exhaust from 2 to 32 minutes of desflurane administration. Just before
      rewarming, final (maximum) washin samples were taken. On rewarming, desflurane
      was discontinued, and blood and gas samples were taken 2 to 24 minutes
      thereafter. MEASUREMENTS AND MAIN RESULTS: CPB time was 116 +/- 10 minutes, and
      ischemic time was 81 +/- 6 minutes. Mean pump flow was 4.49 +/- 0.03 L/min, and
      mean arterial pressure was 70.1 +/- 1 mmHg during the study period. Arterial
      washin of desflurane was initially rapid; arterial concentrations reached 50% of
      administered concentrations within 4 minutes, but then slowed, reaching 68% of
      inspired concentrations at 32 minutes (desflurane concentration 4.0% +/- 0.3%).
      Arterial washout of desflurane was more rapid; arterial concentrations fell to
      18% of the maximum concentration reached within 4 minutes, and only 8% of the
      maximum arterial concentration was present in blood 20 minutes later. CONCLUSION:
      Desflurane showed rapid initial washin and washout on CPB when administration was
      started at 32 degrees C and stopped at time of rewarming.

PMID- 11312476
TI  - Flow dependency of error in thermodilution measurement of cardiac output during
      acute tricuspid regurgitation.
AB  - OBJECTIVE: To evaluate the effect of variable degrees of tricuspid regurgitation
      on thermodilution cardiac output measurements during changes in venous return.
      DESIGN: Prospective, controlled animal study. SETTING: University laboratory.
      PARTICIPANTS: Eight anesthetized mongrel dogs instrumented for simultaneous
      measurement of cardiac output by thermodilution and ascending aortic
      electromagnetometry. INTERVENTIONS: Data were collected before and after
      induction of moderate and severe tricuspid regurgitation. Under each condition,
      measurements were obtained at baseline and after opening 2 peripheral
      arteriovenous shunts to increase venous return. MEASUREMENTS AND MAIN RESULTS:
      Baseline electromagnetic flow ranged from 1.74 to 3.62 L/min (median 2.73 L/min).
      Moderate and severe regurgitation reduced median electromagnetic flow values by
      31% and 51%. Applying generalized estimating equations to model thermodilution
      cardiac output as a function of electromagnetic flow, arteriovenous shunt, and
      severity of tricuspid regurgitation revealed that (1) moderate and severe
      regurgitation changed the slope and intercept of the
      thermodilution/electromagnetic regression, but the differences between them were
      not significant, and (2) arteriovenous shunt alone had no effect under any
      condition. A simplified model independent of shunt and containing just 2 levels
      of tricuspid regurgitation (none or present) crossed with electromagnetic flow
      was applied. This analysis showed that regurgitation caused thermodilution to
      significantly underestimate electromagnetic flow at cardiac outputs > 2.27 L/min
      (99 mL/kg/min) and overestimate it at flows < 1.02 L/min (44 mL/kg/min).
      CONCLUSIONS: These data show that acute tricuspid regurgitation may produce
      underestimation of cardiac output by thermodilution when flow is relatively high,
      produce overestimation when flow is relatively low, or have minimal effect when
      flow is in the midrange.

PMID- 11312477
TI  - The effects of volatile anesthetics on the Q-Tc interval.
AB  - OBJECTIVE: To examine the effects of halothane, isoflurane, and sevoflurane on Q
      Tc interval (corrected for heart rate) during inhalation induction of anesthesia.
      DESIGN: Prospective, double-blind, randomized study. SETTING: Departments of
      Cardiology and Anesthesiology in a university hospital. PARTICIPANTS: Patients
      undergoing noncardiac surgery. INTERVENTIONS: A total of 65 American Society of
      Anesthesiologists physical status I-II patients, aged 16 to 50 years, undergoing
      general anesthesia, were randomly allocated to receive halothane, isoflurane, or
      sevoflurane. MEASUREMENTS AND MAIN RESULTS: The time to reach the predetermined
      end-tidal concentrations of 3 minimum alveolar concentration was 6 to 10 minutes.
      When compared with preinduction values, heart rate decreased after halothane (p <
      0.01) and sevoflurane (p < 0.05) administration; in contrast, heart rate
      increased after induction of anesthesia with isoflurane (p < 0.05). The mean QRS
      intervals were not significantly changed after halothane, isoflurane, or
      sevoflurane. The Q-Tc interval was increased with isoflurane compared with
      baseline (465 +/- 23 v 441 +/- 18 msec, p < 0.01), not changed with sevoflurane
      (441 +/- 17 v 434 +/- 19 ms, p > 0.05), and shortened with halothane (426 +/- 23
      v 445 +/- 21 msec, p < 0.01). CONCLUSION: Sevoflurane or halothane may be
      preferred to isoflurane in patients with conditions that are known to induce a
      prolonged Q-Tc interval. The effects of Q-Tc interval changes resulting from
      different anesthetic agents on morbidity and the incidence of arrhythmias during
      anesthesia warrant further investigation.

PMID- 11312478
TI  - Evaluation of transesophageal atrial pacing in the prone and lateral positions.
AB  - OBJECTIVE: To develop recommendations for positioning the second-generation
      pacing esophageal stethoscope for transesophageal atrial pacing in patients
      positioned prone (P), right lateral decubitus (RLD), and left lateral decubitus
      (LLD). DESIGN: Prospective; patients assigned consecutively. SETTING: Tertiary
      and university hospitals. PARTICIPANTS: Thirty (10 in each position group) adult
      patients undergoing surgery. INTERVENTIONS: The optimal depths of insertions
      (DOI) where pacing current threshold was minimal (THmin) were determined first
      when supine, then after positioning. MEASUREMENTS AND MAIN RESULTS:
      Transesophageal atrial pacing was successful in all patients supine and after
      positioning. The optimal DOI varied from 2 cm less deep to 4 cm deeper in
      positioned patients compared with supine patients. Patients positioned P required
      equal or up to 8 mA greater current outputs to achieve transesophageal atrial
      pacing; LLD and RLD patients may require up to 8 mA greater or lesser current
      compared with supine patients. CONCLUSION: Transesophageal atrial pacing can be
      used safely and effectively in patients positioned P, RLD, and LLD.
      Recommendations are presented for positioning the pacing esophageal stethoscope.
      Emphasis is given to using the lowest DOIs and smallest currents to reduce the
      chance of transesophageal ventricular pacing.

PMID- 11312479
TI  - Effect of low-dose milrinone on gastric intramucosal pH and systemic inflammation
      after hypothermic cardiopulmonary bypass.
AB  - OBJECTIVE: To investigate the usefulness of low-dose milrinone on gastric
      intramucosal pH (pHi) and systemic inflammation in patients undergoing
      hypothermic cardiopulmonary bypass (CPB). DESIGN: Prospective randomized study.
      SETTING: University hospital. PARTICIPANTS: Twenty patients scheduled for cardiac
      surgery. INTERVENTIONS: Ten patients were administered a low dose of milrinone,
      0.25 microg/kg/min, from the initiation of CPB to 1 hour after admission to the
      intensive care unit. The other patients were administered saline. Supplemental
      inotropes and intravenous fluid were given to obtain adequate mean arterial blood
      pressure and pulmonary artery occlusion pressure. MEASUREMENTS AND RESULTS:
      Gastric pHi and carbon dioxide pressure (PCO2) were assessed by capnometric air
      tonometry. The difference between PCO2 and arterial carbon dioxide pressure
      (PaCO2), PCO2-gap, was also examined. Systemic inflammatory responses were
      evaluated by serum interleukin-6 and leukocyte counts. Hemodynamics, oxygen
      delivery index, and oxygen uptake index were monitored with catheters in the
      radial and pulmonary arteries (thermodilution). The hepatic venous blood flow and
      left ventricular flow were measured using transesophageal echocardiography.
      Milrinone prevented gastric intramucosal acidosis, detected as a decrease in pHi
      or an increase in PCO2-gap, without affecting hepatic venous blood flow.
      Increases in interleukin-6, leukocyte count, and oxygen uptake index, all of
      which developed after CPB, were significantly less in the milrinone group than in
      the control group. CONCLUSION: These results suggest that in patients undergoing
      hypothermic CPB, supplemental low-dose milrinone prevents gastric intramucosal
      acidosis and increases in some markers of systemic inflammation.

PMID- 11312480
TI  - A beta-blocker, not magnesium, is effective prophylaxis for atrial
      tachyarrhythmias after coronary artery bypass graft surgery.
AB  - OBJECTIVE: To evaluate magnesium as a sole or adjuvant agent with currently used
      prophylactic drugs in suppressing postoperative atrial tachyarrhythmias (POAT)
      after coronary artery bypass graft (CABG) surgery. DESIGN: Single-center
      prospective, randomized clinical trial. SETTING: University hospital.
      PARTICIPANTS: Patients (n = 400) undergoing CABG surgery. INTERVENTIONS: Patients
      were randomized among 6 prophylaxis regimens: (1) control (no antiarrhythmics),
      (2) magnesium only, (3) digoxin only, (4) magnesium and digoxin, (5) propranolol
      only, and (6) magnesium and propranolol. Patients randomized to a regimen
      including magnesium received 12 g given during 96 hours postoperatively. Patients
      in a digoxin regimen received 1 mg after cardiopulmonary bypass and 0.25 mg
      daily. Patients in a propranolol regimen received 1 mg intravenously every 6
      hours until able to take 10 mg orally 4 times a day. Prophylaxis regimens were
      discontinued after 4 days postoperatively. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was a sustained POAT or discharge from the hospital. Control
      patients had an incidence of POAT (38%) not significantly different from patients
      in magnesium-only (38%), digoxin-only (31%), and magnesium with digoxin (37%)
      regimens. Patients treated with propranolol had a significant reduction in POAT.
      Nearly identical POAT rates in the propranolol-only (18%) and propranolol with
      magnesium (19%) groups support the lack of efficacy of magnesium in this trial.
      Study design allowed analysis of and showed a beta-blocker withdrawal effect in
      addition to suppressive benefit of postoperative beta-blockers. CONCLUSION: beta
      Blocker prophylaxis is indicated to reduce the incidence of POAT in CABG surgery
      patients and to prevent a beta-blocker withdrawal effect in patients receiving
      these medications preoperatively. Digoxin and magnesium as sole or adjuvant
      agents do not offer suppressive or ventricular rate reduction benefits in POAT.

PMID- 11312481
TI  - Effects of hypertonic saline (7.5%) on extracellular fluid volumes compared with
      normal saline (0.9%) and 6% hydroxyethyl starch after aortocoronary bypass graft
      surgery.
AB  - OBJECTIVE: To compare the effects of hypertonic (7.5%) saline (HS), normal (0.9%)
      saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid volumes in
      the early postoperative period after cardiopulmonary bypass. DESIGN: A
      prospective, randomized, double-blind study. SETTING: University teaching
      hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary
      artery bypass graft surgery. INTERVENTIONS: Patients were randomly allocated to
      receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was
      needed during the postoperative rewarming period in the intensive care unit.
      Plasma volume was measured using a dilution of iodine-125-labeled human serum
      albumin. Extracellular water and cardiac output were measured by whole-body
      impedance cardiography. MEASUREMENTS AND MAIN RESULTS: Plasma volume had
      increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p =
      0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the
      plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p <
      0.001). The increase of extracellular water was greater than the infused volume
      in the HS and HES groups at the end of the infusion. One-hour diuresis after the
      study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267
      +/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025). CONCLUSION:
      The effect of HS on plasma volume was short-lasting, but it stimulated excretion
      of excess body fluid accumulated during cardiopulmonary bypass and cardiac
      surgery. HS may be used in situations in which excess free water administration
      is to be avoided but the intravascular volume needs correction.

PMID- 11312482
TI  - The relationship between tracheal width and left bronchial width: Implications
      for left-sided double-lumen tube selection.
AB  - OBJECTIVE: To determine if there is a relationship between tracheal width (TW)
      and left bronchial width (LBW). DESIGN: Three-dimensional chest computed
      tomography (CT) scans were used to reconstruct major airways for measurement of
      TW and LBW. SETTING: Stanford University Medical Center, Stanford, California.
      PARTICIPANTS: Thirty-one adult patients undergoing chest CT scans. INTERVENTIONS:
      Cursors were used to directly measure internal diameter from coronal images of
      the trachea at midclavicular level and the left main bronchus at a level 1 cm
      below the carina. MEASUREMENTS AND MAIN RESULTS: TW and LBW, but not the LBW-to
      TW ratio, were significantly larger in men than in women. The LBW-to-TW ratio was
      consistent for men (0.75 +/- 0.09) and women (0.77 +/- 0.10). CONCLUSIONS: LBW is
      proportional to TW. If LBW cannot be measured directly but TW can, the ratio of
      LBW to TW can be used to predict LBW. An appropriate-sized left double-lumen tube
      can then be selected for the patient.

PMID- 11312483
TI  - Inhaled nitric oxide administration during one-lung ventilation in patients
      undergoing thoracic surgery.
AB  - OBJECTIVE: To evaluate the effects of inhaled nitric oxide (iNO) on hemodynamics
      and oxygenation during one-lung ventilation (OLV) in the lateral decubitus
      position in patients undergoing elective thoracic surgery. DESIGN: Prospective
      study. SETTING: University hospital. PARTICIPANTS: Thirty consecutive patients
      scheduled for thoracotomy. INTERVENTIONS: Anesthesia consisted of thoracic
      epidural analgesia combined with general anesthesia (isoflurane, fentanyl, and
      vecuronium bromide). Systemic and pulmonary circulations were monitored with a
      radial artery catheter and a pulmonary artery catheter. Inhaled NO, 40 ppm, was
      administered during OLV, and the inhaled gas mixture was monitored for NO and
      nitrogen dioxide (NO2). Hemodynamic and oxygenation data were collected before
      and during inhaled NO administration. MEASUREMENTS AND MAIN RESULTS: Inhaled NO
      caused a reduction of pulmonary vascular resistance index from 249 +/- 97.6 dyne.
      sec. cm(-5) to 199.3 +/- 68.9 dyne. sec. cm(-5) (p < 0.05), without effects on
      systemic hemodynamics or impairment of oxygenation. A stratification of the
      patients according to values of QS/QT (< 30%, 30% to 44%, > or = 45%),
      PaO(2)/fraction of inspired oxygen (> or = 200, 100 to 199, < 100), and pulmonary
      hypertension (mean pulmonary arterial pressure < 24 or > or = 24 mmHg) showed
      that inhaled NO causes a significant reduction of mean pulmonary artery pressure
      in patients with pulmonary hypertension, mainly as a result of a reduction of
      pulmonary vascular resistance index, and improves oxygenation by reducing
      intrapulmonary shunt in patients with severe hypoxemia during OLV. CONCLUSIONS:
      Inhaled NO administration neither significantly decreased mean pulmonary arterial
      pressure in patients with normal pulmonary artery pressure nor improved
      oxygenation in nonhypoxic patients. Nevertheless, inhaled NO is effective in
      patients with pulmonary hypertension and hypoxemia during OLV.

PMID- 11312484
TI  - Hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide
      and inhaled aerosolized prostacyclin.
AB  - OBJECTIVE: To evaluate hemodynamic and oxygenation changes of combined therapy
      with inhaled nitric oxide (iNO) and inhaled aerosolized prostcyclin (IAP) during
      lung transplantation. DESIGN: Prospective study. SETTING: University hospital.
      PARTICIPANTS: Ten patients scheduled for lung transplantation. INTERVENTIONS: Ten
      patients, with a mean age of 38 years (range, 24 to 56 years), were scheduled for
      lung transplantation (2 single-lung transplantations and 8 double-lung
      transplantations). During first lung implantation with single-lung perfusion and
      ventilation, hemodynamic and oxygenation data were analyzed in 3 phases: (1)
      baseline, 5 minutes after pulmonary artery clamping; (2) inhaled NO phase, 15
      minutes after inhaled NO administration (20 ppm) in 100% oxygen; and (3) IAP
      inhaled NO phase, 15 minutes after combined administration of inhaled NO (20 ppm)
      and IAP (10 ng/kg/min) in 100% oxygen. MEASUREMENTS AND MAIN RESULTS: During the
      inhaled NO phase, reductions of mean pulmonary arterial pressure (p < 0.05) and
      intrapulmonary shunt (p < 0.05) were noted. After the start of prostacyclin
      inhalation, a further decrease in mean pulmonary arterial pressure (p < 0.05) was
      observed. PaO2/FIO2 increased during the IAP-inhaled NO phase (p < 0.05), whereas
      intrapulmonary shunt decreased (p < 0.05). CONCLUSION: This study confirms the
      action of inhaled NO as a selective pulmonary vasodilator during lung
      transplantation. Combined therapy with IAP and inhaled NO increases the effects
      on pulmonary arterial pressure and oxygenation compared with inhaled NO
      administered alone without any systemic changes.

PMID- 11312485
TI  - Intraoperative ultrasound for localization of patent left internal mammary artery
      grafts in repeat cardiothoracic surgery.

PMID- 11312486
TI  - Carotid artery-internal jugular vein fistula: A complication of internal jugular
      vein catheterization.

PMID- 11312487
TI  - Mediastinal mass resection: Femorofemoral cardiopulmonary bypass before induction
      of anesthesia in the management of airway obstruction.

PMID- 11312488
TI  - Platelet glycoprotein IIb/IIIa antagonists: perioperative implications.

PMID- 11312489
TI  - Advances in neuromonitoring for cardiothoracic and vascular surgery.

PMID- 11312490
TI  - Case 5--2001. Port-access cardiac surgery and aortic dissection: the role of
      transesophageal echocardiography.

PMID- 11312491
TI  - Pro: Intraoperative use of nitric oxide for treatment of pulmonary hypertension
      in patients with congenital heart disease is effective.

PMID- 11312492
TI  - Con: Intraoperative use of nitric oxide for treatment of pulmonary hypertension
      in patients with congenital heart disease is not effective.

PMID- 11312493
TI  - Right atrial mass in a neonate.

PMID- 11312494
TI  - Location of an intra-aortic balloon pump.

PMID- 11312495
TI  - Anesthesia for ventricular assist device placement.

PMID- 11312497
TI  - Safe central venous access and transesophageal echocardiography.

PMID- 11312498
TI  - Utility of transesophageal echocardiography in the management of retained left
      atrial catheter.

PMID- 11312499
TI  - Support for ondansetron use.

PMID- 11312500
TI  - Toxicological screening of urine for drugs by liquid chromatography/time-of
      flight mass spectrometry with automated target library search based on elemental
      formulas.
AB  - The present study describes a novel approach for utilizing liquid
      chromatography/time-of-flight mass spectrometry (LC/TOFMS) in qualitative
      screening analysis. An LC/TOFMS method was developed for screening
      toxicologically relevant substances in urine samples. After solid phase
      extraction and LC separation, the method included full spectrum acquisition
      followed by automatic internal calibration, searching against a target library,
      and reporting positive identifications. The target library, containing 433
      toxicologically relevant substances in the mass range of 105-734 Da, was created
      simply by entering the elemental formulas of substances into the instrument
      software for the calculation of their respective monoisotopic masses. In addition
      to parent drugs, the library contained selected urinary drug metabolites, based
      on their structures available in the literature. Identification was based on the
      exact masses of the compounds. The LC/TOFMS method provided 5-10 ppm mass
      accuracy for a majority of identified compounds in authentic urine samples.
      Compared with established thin-layer and gas chromatographic methods, the
      LC/TOFMS method produced similar findings in urine with the additional advantage
      of metabolite identification without actual reference substances.

PMID- 11312501
TI  - A novel approach for identification and measurement of hemoglobin adducts with
      1,2,3,4-diepoxybutane by liquid chromatography/electrospray ionisation mass
      spectrometry and matrix-assisted laser desorption/ionisation tandem mass
      spectrometry.
AB  - The structural characterisation of the adducts formed by in vitro interaction of
      hemoglobin (Hb) with 1,2,3,4-diepoxybutane (DEB), the most reactive 1,3-butadiene
      (BD) metabolite, was obtained by liquid chromatography/electrospray ionisation
      mass spectrometry (LC/ES-MS) analysis of modified tryptic peptides of human
      hemoglobin chains. The reactive sites of human hemoglobin towards DEB and its
      hydroxylated derivatives (trihydroxybutyl (THB)-derivatives) were identified
      through the characterisation of alkylated tryptic peptides by matrix-assisted
      laser desorption/ionisation tandem mass spectrometry (MALDI-MS/MS). Based on this
      characterisation, a procedure was set up to measure the Hb-adducts of THB
      derivatives by isotope dilution mass spectrometry with the use of a deuterated
      peptide standard. The results obtained here could permit optimisation of
      molecular dosimetry of BD-adducts, and extension of the analysis to the
      biological monitoring of occupational exposure to butadiene.

PMID- 11312502
TI  - On the fragmentation pathway of the ionized enol of glycine in the gas phase.
AB  - Density functional and second-order many body perturbation approaches were used
      to compute the potential energy surface for the fragmentation of the ionized enol
      of glycine [H2NCH = C(OH)2]+* into water and aminoketene radical cation [H2N-HC =
      CO]+*. Two possible pathways were considered. The potential energy surfaces
      obtained are very similar and both predict the existence of a molecular complex
      in which the water is coordinated to the aminoketene moiety in two different
      fashions with a noticeable binding energy. The fragmentation is kinetically
      controlled by the step in which the molecular complex is formed from the most
      stable cation enol of glycine. Our quantum-mechanical data confirm the hypothesis
      that the ylide ion [H3NCHCOOH]+* is an intermediate in the water loss.

PMID- 11312503
TI  - High-throughput analysis in drug discovery: application of liquid
      chromatography/ion-trap mass spectrometry for simultaneous cassette analysis of
      alpha-1a antagonists and their metabolites in mouse plasma.
AB  - The application of liquid chromatography/ion-trap mass spectrometry for
      simultaneous quantification of multiple drugs and detection of their metabolites
      for in vitro experiments was reported recently. In the current study, the use of
      these techniques was extended to in vivo pharmacokinetic (PK) studies of alpha-1a
      antagonists. In combination with limited time-point PK, greatly increased
      throughput was demonstrated for the in vivo screening and investigation of in
      vivo-in vitro correlation. In addition to quantitative analyses, the technique
      allowed simultaneous detection of major in vivo metabolites without having to
      reanalyze the plasma samples. The drugs were individually dosed in mice
      intravenously via tail vein injection and the blood samples were collected 5 min
      and 2 h after dosing. After the plasma samples for the different drugs had been
      prepared separately, they were pooled for cassette analysis. The concentrations
      of five test compounds in the plasma samples at 2 h ranged from 36-1062 ng/mL,
      whereas their 5-min plasma levels were similar. From the same cassette analysis,
      major metabolites in the samples were also detected simultaneously through the
      interpretation of full-scan mass spectra. The metabolite identification confirmed
      the results from a previous report that the major sites of metabolism are
      hydroxylation of the phenyl ring not bearing the alkylsulfonamide substitutent,
      piperidine N-dealkylation, and N-demethylation of the alkylsulfonamide group.

PMID- 11312504
TI  - Reactivity of anomeric 1alpha- and 1beta-pentofuranosyl azide derivatives in
      ammonia chemical ionization.
AB  - Electron impact (EI), fast atom bombardment (FAB) and ammonia chemical ionization
      [CI(NH3)] mass spectrometry were applied with the aim of differentiating between
      the anomeric 1alpha- and 1beta-azidopentofuranosyl derivatives. Calculated
      ammonium affinities [AA(M)] and proton affinities [PA(M)] show that beta-anomers
      have higher affinities for H+ and NH4+ ions than alpha-azides. Protonated
      molecules, obtained by CI(NH3) of azidofuranosyl derivatives, lose HN3 giving
      abundant furanosyl (S+) ions. Ammonia solvation of MH+ ions competes with the
      previous reaction producing the [SNHN2NH3]+ ion, a competitive product to the
      ammonium-attached [SN3NH4]+ ion. The fragmentation pathways of the stable and
      metastable [MNH4]+, MH+ ions, and several other important fragment ions, were
      determined using mass analyzed ion kinetic energy spectrometry (MIKES). The
      abundance of the [SN3NH4]+ and/or [SNHN2NH3]+ ions was found to correlate
      inversely with the exothermicity of ammonia solvation of the MH+ ion. The
      abundance of the fragment ions [SNHNH3]+, [SNH3]+ and SNH+ in some examples
      correlates with the exothermicity of the corresponding [MNH4]+ and MH+ parent ion
      formation. The fragment ions SNH3+ and SNHNH3+ can be formed, at least in part,
      in the ammonia solvation reaction of the S+ and SNH+ ions taking place within the
      high-pressure region of the CI ion source.

PMID- 11312505
TI  - On-line measurement of the absolute humidity of air, breath and liquid headspace
      samples by selected ion flow tube mass spectrometry.
AB  - We describe how selected ion flow tube mass spectrometry (SIFT-MS) can be used to
      determine the absolute humidity of air, breath and liquid headspace samples. This
      involves the determination of the relative count rates of the H3O+ ions and those
      H3O+.(H2O)(1,2,3) hydrate ions that inevitably form in the helium carrier gas
      when humid samples are being analysed by SIFT-MS using H3O+ precursor ions. This
      requires an understanding of the kinetics of hydrated hydronium ion formation,
      the involvement of mass discrimination in the analytical quadrupole mass
      spectrometer and the decreased diffusive loss of the heavier hydrates along the
      flow tube. Thus, we show that the humidity of breath and liquid headspace
      samples, typically at the few percent level, can be directly obtained on-line to
      the SIFT-MS instrument along with the concentrations of trace gases, which are
      present at much lower levels. We emphasise the value of parallel humidity
      measurements in ensuring good real-time sampling of breath and liquid headspace
      and the value of such measurements to trace gas analysis using SIFT-MS.

PMID- 11312506
TI  - A new approach to data reduction and evaluation in high-resolution time-of-flight
      mass spectrometry using a time-to-digital convertor data-recording system.
AB  - A new effective and robust approach to the detection of incompletely resolved
      peaks, and evaluation of their parameters in high-resolution time-of-flight mass
      spectra for time-to-digital convertor (TDC) data acquisition mode, is described.
      The method is based on fast construction of a smoothed continuous curve that
      approximates the initial data (transformed to a constant relative width of time
      intervals for ion counting) with respect to precision of measurements. The first
      derivative of this curve is used for correction of skewness of the peak shape as
      far as possible. A contribution of the second derivative is subtracted from the
      smoothed curve for better resolution of partially resolved peaks. The comparison
      of local maxima of this resulting final curve with those for the initial smoothed
      curve allows reliable detection of the peaks and to test whether or not they are
      spoiled by overlapping. Ion counting performed by TDC gives an opportunity to
      estimate standard deviations of peak locations and their intensities. These
      values proved to be close to theoretically minimal standard deviations for these
      parameters for single fully resolved peaks. Thus, estimates of the main
      parameters of mass peaks by the described method are close to statistically
      efficient estimators for these parameters.

PMID- 11312507
TI  - Conformational study of a new SGTx1 neurotoxin from the spider Scodra griseipes
      using mass spectrometry.
AB  - SGTx1 is a new neurotoxin from the venom of Scodra griseipes. Because of the
      small quantity of this natural peptide available, mass spectrometry was used to
      obtain information on its higher-order structure. The kinetics of reduction by
      1,4-dithiothreitol (DTT) was monitored by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), and showed
      that one of the three disulfide bridges was appreciably more accessible to the
      DTT. Studies based on the charge state distribution (CSD) and H/D exchange of the
      non-reduced peptide, under neutral and acidic conditions, were performed using
      electrospray mass spectrometry (ES-MS). In neutral solution, SGTx1 showed a
      maximum charge state of four compared with seven potentially protonated basic
      residues, and all labile hydrogens were exchanged. However, under acidic
      conditions, a maximum charge state of only five was observed, and four of the
      labile hydrogens could not be deuterated. These observations are interpreted in
      terms of a rigid structure maintained by the disulfide bridges, which can be
      temporarily relaxed by disulfide bridge scrambling only at higher pH values.

PMID- 11312508
TI  - Metal ion adducts in the structural analysis of ginsenosides by electrospray
      ionization with multi-stage mass spectrometry.
AB  - The effect of metal (Li+, Na+, K+, Ag+) cationization on collision-induced
      dissociation of ginsenosides was investigated by electrospray ionization mass
      spectrometry combined with multi-stage mass spectrometry (ESI-MS(n)). The
      fragments of sodiated and lithiated molecules give valuable structural
      information regarding the nature of the aglycone and the sequence and linkage
      information of sugar moieties. However, the number and relative abundances of
      fragment ions from lithiated ginsenosides are significantly greater than for the
      sodiated species. The K+ adducts undergo glycosidic cleavages and very limited
      cross-ring reactions. The silver ion adducts fragment mainly through glycosidic
      cleavages.

PMID- 11312509
TI  - The effect of the source pressure on the abundance of ions of noncovalent protein
      assemblies in an electrospray ionization orthogonal time-of-flight instrument.
AB  - The effect of elevating the pressure in the interface region of an electrospray
      ionization orthogonal time-of-flight mass spectrometer on the ion intensity of
      different noncovalent protein assemblies has been investigated. Elevating the
      pressure in the interface region generally led to an enhanced detection of high
      m/z ions. The optimum pressure was found to be dependent on the m/z value of the
      ions. This pressure effect should be carefully addressed when relating ion
      abundance in the mass spectra to solution phase abundance of noncovalent protein
      assemblies.

PMID- 11312510
TI  - Detection of sulfur-containing impurities in pharmaceutical samples by high
      performance liquid chromatography/chemical reaction interface mass spectrometry.
AB  - This paper describes the use of chemical reaction interface mass spectrometry
      (CRIMS) combined with liquid chromatography for the detection of trace level
      sulfur-containing impurities in pharmaceutical materials. A mixture of sulfur-
      and non-sulfur-containing compounds were analyzed initially to test the system.
      Then the determination of trace level impurities in a cimetidine drug substance
      was carried out. Detection of sulfur-containing impurities at less than 0.1% of
      the major component was obtained with good linearity. The results obtained are
      consistent with the expected results for this sample and illustrate the
      applicability of the technique.

PMID- 11312511
TI  - An experimental comparison of electrospray ion-trap and matrix-assisted laser
      desorption/ionization post-source decay mass spectra for the characterization of
      small drug molecules.
AB  - An experimental comparison of product ion spectra produced by matrix-assisted
      laser desorption/ionization (MALDI) and electrospray ion-trap MS( n) for a group
      of small drug molecules is presented in this paper. The goal of the study was to
      demonstrate the usefulness of MALDI-MS with post-source decay (PSD) and collision
      induced dissociation (CID) for the structural analysis of small drug molecules in
      the drug discovery process, where traditionally electrospray LC/MS methods are
      used. PSD and PSD/CID gave diverse product ions that were highly indicative of
      the structure of the drugs investigated (a group of 4-quinolone antibiotics and
      oleandomycin). In addition, the number of different product ions generated with
      MALDI-MS was always higher than with electrospray ion-trap MS( n) (with n < or
      =4) for the drug molecules studied. This investigation also showed that the
      choice of a suitable MALDI matrix for the analysis of low molecular weight
      compounds is quite important. It was found that of the three matrices examined,
      alpha-cyano-4-hydroxycinnamic acid (alpha-CHCA) produced the most intense
      fragmentation levels while TiO2, with its advantage of virtually no low mass
      background signals, did not generate quite the same amount of information.

PMID- 11312512
TI  - Gas phase attachment of water and methanol to Ag(I) complexes with alpha-amino
      acids in an ion trap mass spectrometer.
AB  - Electrospray ionization was used to generate gas phase complexes of Ag+ with
      selected alpha-amino acids. Following storage (isolation without collisional
      activation) in an ion trap mass spectrometer, the mass spectra produced from the
      complexes of Ag+ with alpha-amino acids such as alanine, valine and tert-leucine
      contained peaks consistent with the formation of water or methanol molecule
      adduct ions. The same adduct ions were not present, however, in the mass spectra
      generated from the Ag+ complexes with phenylalanine, tyrosine and tryptophan
      following isolation and storage under similar conditions. For those complexes
      that showed reactivity, the uptake of water and methanol increased with longer
      storage times in the ion trap. A preliminary molecular modeling study using
      phenylalanine demonstrated that the aromatic ring coordinates the Ag+ ion, and
      the interaction between the metal ion and pi-system, in part, is assumed to
      prohibit the binding of water or methanol during isolation in the gas phase. This
      conclusion is supported by a comparison of the adduct formation by the Ag+
      complexes with phenylalanine, 4-fluorophenylalanine and alpha
      aminocyclohexanepropionic acid. In addition, collision induced dissociation
      experiments involving the Ag+ complexes of phenylalanine, tyrosine and tryptophan
      suggest that limiting the coordination of the Ag ion by the complexing molecule
      (i.e. by loss of a coordinating functional group and/or change in structure due
      to dissociation) results in the binding of a water or methanol molecule during
      storage in the ion trap. Surprisingly, the bare Ag+ ion, when trapped and stored
      under identical experimental conditions, formed neither adduct species,
      suggesting that the attachment of water or methanol may be due to interactions
      with a molecular orbital within the Ag+/molecule complex.

PMID- 11312513
TI  - Analysis of bacterial lipodepsipeptides by matrix-assisted laser
      desorption/ionisation time-of-flight and high-performance liquid chromatography
      with electrospray mass spectrometry.
AB  - Strains of certain plant pathogenic bacteria, in particular several pathovars of
      Pseudomonas syringae, are known to produce cyclic lipodepsipeptides (LDPs)
      endowed with peculiar structural features and noticeable biological activities.
      In this study, a mass spectrometry procedure is proposed for screening LDP
      producing bacterial strains and for identifying and assessing individual LDPs.
      After matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF)
      screening of thirteen P. syringae strains for LDP production, the extracts from
      culture filtrates of eight positive strains were subjected to electrospray mass
      spectrometry for the identification of LDPs. Five strains were found to produce
      two forms of syringomycins (SR-E and SR-G) and two forms of syringopeptin 25
      (SP25A and SP25B); two strains produced SR-E, SR-G and a new form of SP22; one
      strain produced syringotoxin (ST) and syringostatin A (SS-A) in addition to SP25A
      and SP25B. The yield in culture of two major LPDs: SR-G (3.2-13.8 mg x L(-1)) and
      SP25A (41.6-231.5 mg x L(-1)) was assessed by and high-performance liquid
      chromatography with electrospray mass spectrometry (HPLC/ESI-MS) in both scan and
      single ion monitoring (SIM) modes. Results of this investigation showed that the
      mass spectrometry protocol developed here is a precise and reliable method for
      screening bacterial strains for LDP production and for assessing the amount of
      each metabolite under various culture conditions. This could be of practical
      value in view of potential applications, e.g. biocontrol of post-harvest fungal
      diseases.

PMID- 11312514
TI  - A strategy for quantitative bioanalysis of non-polar neutral compounds by liquid
      chromatography/electrospray ionization tandem mass spectrometry: determination of
      TS-962, a novel acyl-CoA:cholesterol acyltransferase inhibitor, in rabbit aorta
      and liver tissues.
AB  - A strategy for the sensitive and reliable quantitative determination of non-polar
      neutral compounds in biological matrices by liquid chromatography/electrospray
      ionization tandem mass spectrometry is described in the context of assay
      development for TS-962, a novel acyl-CoA:cholesterol acyltransferase (ACAT)
      inhibitor, in rabbit aorta and liver tissues. The electrospray ionization (ESI)
      mass spectrum of this compound with a mobile phase of water/acetonitrile did not
      give abundant [M + H]+ ions, but did give alkali metal cation adducts such as [M
      + Na]+, [M + CH3CN + Na]+ and [M + K]+ ions. The cationized species are
      acknowledged as unsuitable precursor ions for selected reaction monitoring (SRM)
      for various reasons, such as difficulty in obtaining characteristic product ions
      in low-energy collision-induced dissociation, and irreproducibility of the adduct
      ion intensities. To overcome this problem, a solution of 3.4 mM trifluoroacetic
      acid in 2-propanol was added to the mobile phase as a postcolumn additive,
      resulting in a decrease of the undesirable adduct formation and significant
      enhancement of [M + H]+ ion intensity. An attempt was then made to prevent the
      matrix effect by employing a column-switching system, which allowed direct
      injection of a large volume of 2-propanolic tissue homogenate (950 microL)
      followed by sufficient clean-up, separation, and ESI-SRM on-line. This enabled
      development of a sensitive and reliable assay method for TS-962 in rabbit aorta
      and liver tissues in the concentration range of 5-500 ng/g wet tissue using a 25
      mg aliquot of tissue sample. Application of this method to the determination of
      aortic TS-962 levels at 24 h after repeated oral administration of this compound
      (3 mg/kg) once a day for 12 weeks to 1% cholesterol-fed rabbits is also
      presented. Results showed that TS-962 is well distributed to both the thoracic
      and abdominal aorta tissues, at levels higher than the 50% inhibitory
      concentration value of this compound for microsomal ACAT activity from rabbit
      aorta.

PMID- 11312515
TI  - Proton mobility in protonated glycylglycine and N-formylglycylglycinamide: a
      combined quantum chemical and RKKM study.
AB  - Theoretical model calculations were performed to investigate the degree of
      validity of the mobile proton model of protonated peptides. The structures and
      energies of the most important minima corresponding to different structural
      isomers of protonated diglycine and their conformers, as well as the barriers
      separating them, were determined by DFT calculations. The rate coefficients of
      the proton transfer reactions between the isomers were calculated using the RRKM
      method in order to obtain a quantitative measure of the time scale of these
      processes. The proton transfer reactions were found to be very fast already at
      and above the threshold to the lowest energy decomposition pathway. Two possible
      mechanisms of b2+-ion formation via water loss from the dipeptide are also
      discussed. The rate-determining step of the proton migration along a peptide
      chain is also investigated using the model compound N-formylglycylglycinamide.
      The investigations revealed that this process very possibly occurs via the
      protonation of the carbonyl oxygens of the amide bonds, and its rate-determining
      step is an internal rotation-type transition of the protonated C=O-H group
      between two adjacent C=O-HellipsisO=C bridges.

PMID- 11312516
TI  - Theoretical study of the main fragmentation pathways for protonated
      glycylglycine.
AB  - Quantum chemical and RRKM calculations were carried out on protonated
      glycylglycine in order to determine the atomic details of the main fragmentation
      pathways leading to formation of a1 and y1 ions. Two possible mechanisms were
      considered. The first path results in elimination of aziridinone as a neutral
      counterpart of the y1 ion formed. Our calculations show that this pathway has a
      relatively high threshold energy (48.6 kcal/mol) and the corresponding
      unimolecular rate constants are quite small even at large internal energy. An
      alternative pathway (a1-y1) proposed in the present paper seems, however, to be
      favored against the above 'aziridinone' one from the points of view of both
      energetics and kinetics. The 'a1-y1' pathway leads to simultaneous formation of
      a1 and y1 ions, the ratio of which depends on the energy distribution of the
      fragmenting species for a particular dipeptide. However, even if y1 ions are
      formed via the 'a1-y1' pathway, the corresponding neutrals eliminated do not have
      a strained cyclic aziridinone structure. Instead, in a two-step process, CO and
      NHCH2 are formed leading to neutral products energetically more favored than
      aziridinone. The available experimental data reevaluated in the present paper
      lend support to the 'a1-y1' pathway.

PMID- 11312517
TI  - MassKinetics: a theoretical model of mass spectra incorporating physical
      processes, reaction kinetics and mathematical descriptions.
AB  - A theoretical framework and an accompanying computer program (MassKinetics,
      www.chemres.hu/ms/ masskinetics) is developed for describing reaction kinetics
      under statistical, but non-equilibrium, conditions, i.e. those applying to mass
      spectrometry. In this model all the important physical processes influencing
      product distributions are considered: reactions, including the effects of
      acceleration, collisions and photon exchange. These processes occur
      simultaneously and are taken into account by the master equation approach. The
      system is described by (independent) product, kinetic energy and internal energy
      distributions, and the time development of these distributions is studied using
      transition probability functions. The product distribution at the end of the
      experiment corresponds to the mass spectrum. Individual elements in this scheme
      are mostly well known: internal energy-dependent reaction rates are calculated by
      transition state theory (RRK or RRKM formalisms). In the course of collisions,
      energy transfer and other processes may occur (the latter usually resulting in
      the 'loss' of ion signal). Collisions are characterized by their probability and
      by energy transfer in a single collision. To describe single collisions, three
      collision models are used: long-lived collision complexes, partially inelastic
      collisions and partially inelastic collisions with cooling. The latter type has
      been developed here, and is capable of accounting for cooling effects occurring
      in collision cascades. Descriptions of photon absorption and emission are well
      known in principle, and these are also taken into account, in addition to changes
      in kinetic energy due to external (electric) fields. These changes in the system
      occur simultaneously, and are described by master equations (a set of
      differential equations). The usual form of the master equation (taking into
      account reactions and collisional excitation) was extended to consider also
      radiative energy transfer, kinetic energy changes, energy partitioning and ion
      loss collisions. Initial results show that close to experimental accuracy can be
      obtained with MassKinetics, using few or no adjustable parameters. The
      model/program can be used to model almost all types of mass spectrometric
      experiments (e.g. MIKE, CID, SORI and resonant excitation). Note that it was
      designed for mass spectrometric applications, but can also be used to study
      reaction kinetics in other non-equilibrium systems.

PMID- 11312518
TI  - Solvation of acylium fragment ions in electrospray ionization quadrupole ion trap
      and Fourier transform ion cyclotron resonance mass spectrometry.
AB  - In electrospray ionization (ESI) quadrupole ion trap and Fourier transform ion
      cyclotron resonance mass spectrometry, certain fragment ions (e.g. acylium ions)
      generated either during the ion transportation process (in the source interface
      region) or in the ion trap are found to undergo ion--molecule reactions with ESI
      solvent molecules (water, acetonitrile and aliphatic alcohols) to form adduct
      species. These unexpected solvated fragment ions severely complicate the
      interpretation of mass spectrometic data. High-resolution accurate mass
      measurements are important in establishing the elemental compositions of these
      adduct species and preventing erroneous data interpretation.

PMID- 11312519
TI  - Analysis of alcohols, as dimethylglycine esters, by electrospray ionization
      tandem mass spectrometry.
AB  - Dimethylglycine (DMG) esters are new derivatives for the rapid, sensitive and
      selective analysis of primary and secondary alcohols, in complex mixtures, by
      electrospray ionization tandem mass spectrometry (ESI-MS/MS). Their development
      was inspired by the use of the complementary dimethylaminoethyl esters for the
      trace, rapid analysis of fatty acids. DMG esters are simply prepared by heating a
      dichloromethane solution of the imidazolide of dimethylglycine, containing
      triethylamine, and an alcohol. DMG esters of long-chain fatty alcohols,
      isoprenoidal alcohols and hydroxy-acids are analysed by electrospray ionization
      tandem mass spectrometry with a precursor ion of m/z 104 scan. Diols, glyceryl
      esters, glyceryl ethers and some sterols are analysed by a neutral loss of 103 Da
      scan. Trimethylglycine (TMG) ester iodides, prepared by alkylation of DMG esters
      with methyl iodide, are more sensitive derivatives for molecules containing
      secondary alcohol groups, such as cholesterol and gibberellic acid. They are
      analysed by a precursor ion of m/z 118 scan. DMG or TMG derivatives were shown to
      be at least comparable and sometimes an order of magnitude more sensitive than N
      methylpyridyl ether derivatives for ESI-MS/MS analysis of the different classes
      of alcohols. Applications of these derivatives for the diagnosis of inherited
      disorders and the analysis of natural products are presented.

PMID- 11312520
TI  - Reactions of actinide ions with ethylene oxide.
AB  - Naked and oxo-ligated actinide (An) monopositive ions were reacted with ethylene
      oxide, cyclo-C(2)H(4)O (EtO). Along with An = U, Np, Pu and Am, ions of two
      lanthanide (Ln) elements, Ln = Tb and Tm, were studied for comparison. Metal and
      metal oxide ions, M(+), MO(+) and MO(2)(+), were generated by laser ablation and
      immediately reacted with EtO. Unreacted and product ions were detected by time-of
      flight mass spectrometry. It was apparent that the overall reaction cross
      sections decreased in the order U(+) > or = Np(+) > Pu(+) > Am(+). A primary
      reaction channel for each studied metal was the formation of MO(+) from M(+), in
      accord with the expected exothermicity of oxygen abstraction from EtO. For U, Np
      and Pu, the dioxides were also major products, indicating OAn(+)--O dissociation
      energies of at least 350 kJ mol(-1), the energy required for O-atom abstraction
      from EtO. For Am, Tb and Tm, the dioxides were only very minor products,
      reflecting the stabilities of the trivalent states and resistance to oxidation to
      higher valence states; the structures/bonding in these MO(2)(+) are intriguing
      given that the formal pentavalent bonding state is effectively unattainable. It
      was demonstrated that EtO, unlike more thermochemically favorable but kinetically
      restricted O-donors, is effective at achieving facile oxidation of actinide metal
      ions to the monoxide, and to the dioxide if the second O-abstraction reaction is
      exothermic. Several intriguing minor products were also identified, most of which
      incorporate metal--oxygen bonding and are attributed to the oxophilicity of the f
      block elements; the contrast to the behavior of first-row d-block transition
      elements is striking in this regard. Particularly noteworthy was the formation of
      MH(4)(+) (and MOH(4)(+)), evidently via abstraction of all four H atoms from a
      single C(2)H(4)O molecule; the structures/bonding in these novel 'hydride'
      species are indeterminate and warrant further attention.

PMID- 11312522
TI  - Density functional computations of proton affinity and gas-phase basicity of
      proline.
AB  - The proton affinity and gas-phase basicity of proline were evaluated by using
      density functional theory coupling the B3-LYP hybrid functional with the extended
      6--311++G** basis set. Cis and trans conformations of the carboxyl moiety for
      both exo and endo ring structures were considered for the neutral proline. The
      results show that the most stable structure of proline has the endo ring
      conformation with the carboxyl group in the cis position. The structure at the
      global minimum is stabilized by an intramolecular hydrogen bond. The nitrogen of
      the ring in the exo form is the preferred protonation site. The calculated proton
      affinity (924.3 kJ mol(-1)) and gas-phase basicity (894.4 kJ mol(-1)) are in very
      good agreement with the experimental counterparts.

PMID- 11312523
TI  - Sequence information, distinction and quantitation of C-terminal leucine and
      isoleucine in ternary complexes of tripeptides with Cu(II) and 2,2'-bipyridine.
AB  - Tripeptides form ternary complexes with Cu(2+) and 2,2'-bipyridine (bpy) that
      self-assemble upon mixing the components in aqueous methanol solution.
      Electrospray ionization (ESI) of the complex solutions provides abundant singly
      charged [Cu(peptide -- H)bpy](+) and doubly charged [Cu(peptide)bpy](2+) ions.
      Collision-induced dissociation (CID) at low ion kinetic energies of several
      tripeptides, AGG, GGA, LGG, GGL, GGI, FGG, GGF, LGF, GLF, GFL, GYA and GAY,
      showed fragments that were indicative of the amino acid sequence in the peptide.
      In addition, CID of single and doubly charged complexes of isomeric tripeptides
      GGL and GGI provided unambiguous distinction of the isomeric leucine and
      isoleucine residues. Leucine peptides eliminated C(3)H(7) radicals from the amino
      acid side-chain whereas isoleucine eliminated C(2)H(5) radicals. CID of gas-phase
      doubly charged peptide complexes in a quadrupole ion trap produced a series of
      singly charged sequence fragments that following isolation and further CID
      furnished distinct fragments that allowed quantitation of leucine and isoleucine
      containing peptides in mixtures.

PMID- 11312524
TI  - Equilenin-2'-deoxynucleoside adducts: analysis with nano-liquid chromatography
      coupled to nano-electrospray tandem mass spectrometry.
AB  - The interaction of 4-hydroxy metabolites of estrogens with DNA leads to the
      formation of DNA adducts. These adducts are believed to play an important role in
      the incidence of breast and endometrial cancer. In order to be able to analyze
      these adducts in in vivo samples a method based upon the coupling of miniaturized
      liquid chromatography (LC) to electrospray tandem mass spectrometry (ES-MS/MS)
      was developed for the analysis of the adducts formed with 4-hydroxyequilenin. In
      vitro synthesized adducts obtained by the reaction of 4-hydroxyequilenin with the
      main 2'-deoxynucleosides were separated on a Hypersyl C(18) BDS nano-HPLC column
      (15 cm x 75 microm i.d.) at a flow-rate of 300 nl min(-1) using gradient elution
      with CH(3)OH--0.2% CH(3)COOH in H(2)O. The column was coupled, in combination
      with a column switching system, to a nano-electrospray interface. Analysis of the
      low- and high-resolution low-energy collision-activated dissociation product ion
      spectra of normal and deuterated adducts supported earlier data demonstrating
      equilenin to form different isomeric adducts, except with thymidine, for which no
      adducts were found. The nano-HPLC column-switching ES-MS system was tested for
      its sensitivity on a triple-quadrupole instrument, and detection limits down to
      197 fg in the single reaction monitoring mode were obtained for semi
      preparatively isolated equilenin--2'-deoxyguanosine adduct.

PMID- 11312526
TI  - Quantitative detection of N(7)-(2-hydroxyethyl)guanine adducts in DNA using high
      performance liquid chromatography/electrospray ionization tandem mass
      spectrometry.
AB  - High-performance liquid chromatography (HPLC) was combined with electrospray
      ionization tandem mass spectrometry (ESI-MS/MS) to develop a sensitive and
      selective method for the quantitative measurement of N(7)-(2-hydroxyethyl)guanine
      (N(7)-HEG) adducts in DNA obtained from ethylene oxide-exposed biological
      samples. Selected reaction monitoring (SRM) was used as the detection mode while
      the fragmentation product ion at m/z 152 generated from the precursor protonated
      N(7)-HEG (m/z 196) was monitored. The detection limits for N(7)-HEG were
      estimated by twofold serial dilution and determined to be 4 fmol in neat standard
      solution and 16 fmol when a matrix effect is considered. When the mass
      spectrometer was operated in the selected ion monitoring mode using only the
      first quadrupole (without MS/MS function), the detection limits increased to 128
      fmol and 1 pmol (when matrix effect is considered), respectively. A good linear
      correlation (R(2) = 0.999) was observed for signal intensities obtained by
      injecting 16 fmol--33 pmol of N(7)-HEG into the HPLC/ESI-MS/MS system. Hep G2
      cells were incubated for 8 h with medium containing various concentrations of
      ethylene oxide (ranging from 0.05 to 5.0 mM). A dose-response relationship was
      established, indicating that the adduct formation increases with the exposure
      level. The method shows potential, although the detection limit needs to be
      lowered for practical applications, for use in monitoring N(7)-HEG formation in
      other biological systems.

PMID- 11312527
TI  - An unusual fragmentation mechanism involving the transfer of a methyl group.

PMID- 11312528
TI  - Current literature in mass spectrometry.

PMID- 11312530
TI  - Mitochondria and calcium homeostasis: a tale of three luminescent proteins.
AB  - In recent years the jellyfish Aequorea victoria has provided the scientific
      community with a pair of tools of exceptional usefulness: aequorin and the green
      fluorescent protein (GFP). Whereas the former has played a major role in the
      study of calcium signalling, the latter has sparked the imagination of
      researchers into a myriad of elegant experiments. The firefly Photinus pyralis
      has also been of great use, providing a third luminescent protein, luciferase,
      which is mostly known for its role as a reporter protein. Concurrent use of these
      three proteins provides a powerful means of elucidating biological processes with
      fine spatio-temporal detail. Here we will illustrate how specific molecular
      engineering of these three proteins provided a set of biological tools capable of
      generating important data in the field of calcium homeostasis. First, we will
      show how the use of specifically targeted aequorin chimeras enabled the
      measurement of regional Ca(2+) concentrations; second, how the use of GFP (and
      derived chromatic mutants) permitted detailed morphological analyses in living
      cells; third, how luciferase was used to analyse energetic requirements at the
      subcellular level. Together, these three experimental approaches have provided
      important details on how mitochondria participate actively in calcium
      homeostasis. A final note regarding clinical implications demonstrates the
      practical usefulness of the data obtained.

PMID- 11312531
TI  - In vivo behaviour of long-circulating liposomes in blood vessels in hamster
      inflammation and septic shock models-use of intravital fluorescence microscopy.
AB  - This study aimed to observe liposome uptake by leukocytes in vivo. The study was
      performed on skin by using a dorsal skin-fold chamber implanted in golden
      hamsters using intravital microscopy. 5 and 6-CF-encapsulated polyethylene
      glycolated liposomes were injected intravenously. The skin microcirculation was
      observed with an intravital Eclipse E800 Nikon microscope (using x40, x80
      magnification) fitted with a Xenon light source and an epifluorescence assembly
      (excitation, 470 nm, FWHM 40 nm; emission, 540 nm, FWHM 40 nm). An ultra-high
      sensitivity videocamera mounted on the microscope projected the image onto a
      monitor, and the images (720 x 576 pixels) were recorded for playback analysis
      with a digital video cassette recorder. An acute inflammatory response was
      obtained by removing one complete layer of skin and the underlying fascia and
      avascular tissue on the opposing side of the flap corresponding to an area
      equivalent to the window aperture. Using this model and set-up, leukocyte rolling
      and adhesion were easily observed and the entry of PEGylated liposomes into
      hamster blood leukocytes was studied for a period of 6 h. PEGylated liposomes
      were clearly identified alone inside the blood flow and inside the leukocytes as
      soon as the inflammatory reaction appeared. This study shows for the first time
      that blood leukocytes in their natural milieu of whole blood are capable of
      interacting with, and taking up, liposomes. This observation is in accordance
      with previous in vitro studies.

PMID- 11312532
TI  - Exploiting sensitive laser-induced fluorescence detection on electrophoretic
      microchips for executing rapid clinical diagnostics.
AB  - Fluorescence is used as a sensitive detection technique for current clinical
      diagnostics procedures involving slab gel separations of DNA. In transferring
      electrophoretic separations to smaller formats, first capillaries and then
      microchips, the size of the sample being separated has decreased considerably,
      making it necessary to routinely detect a few hundred molecules of each component
      in the sample. Laser-induced fluorescence detectors provide high sensitivity and
      can be employed in both direct and indirect modes to detect clinically relevant
      compounds. A number of examples show that there is no loss of clinical diagnostic
      capability in moving these analyses to microchip devices. Microchips also allow
      for parallel processing of samples by incorporating multiple channels in a single
      device, with a number of strategies possible for using LIF detection in these
      multiplex systems.

PMID- 11312534
TI  - Attempt to separate the fluorescence spectra of adrenaline and noradrenaline
      using chemometrics.
AB  - An investigation was conducted on whether the fluorescence spectra of the very
      similar catecholamines adrenaline and noradrenaline could be separated using
      chemometric methods. The fluorescence landscapes (several excitation and emission
      spectra were measured) of two data sets with respectively 16 and 6 samples were
      measured, the smaller data set with higher resolution and i.e. precision. The
      samples were artificial urine (pH approximately equal to 3) spiked with the
      catecholamines in the concentration ranges 40--1200 nmol/L and 5.5--18
      micromol/L, respectively. Unfold partial least squares regression (Unfold-PLSR)
      on the larger data set and parallel factor analysis (PARAFAC) of the six samples
      of the smaller set showed that there was no difference between the fluorescence
      landscapes of adrenaline and noradrenaline. It can be concluded that chemometric
      separation of adrenaline and noradrenaline is not obtainable using this type of
      fluorescence measurement. Raman scatter, which overlaps the catecholamine
      spectra, was shown not to have any influence on the models calculated.

PMID- 11312535
TI  - Interaction study of peptide from VP3 capsid protein of hepatitis A virus through
      monolayers and fluorescence spectroscopy.
AB  - A synthetic peptide with the sequence [Lys113]VP3(110--121): FWRKDLVFDFQV,
      corresponding to an epitope of the VP3 capsid protein of hepatitis A virus (HAV),
      was synthesized by solid phase and characterized. To obtain insight into its
      physicochemical properties and to understand its possible mechanism of action at
      the membrane level, interaction with DPPC or DPPC/DPPG (95/5) liposomes and lipid
      monolayers of DPPC, DPPG, SA, PS, PA and SM were studied by fluorescence
      spectroscopy and Langmuir--Blotgett films technique, respectively. Fluorescence
      studies showed that the peptide was in a hydrophobic environment when DPPC
      liposomes were used. The addition of a 5% of a charged lipid, DPPG, to the
      preparations changed the preference of the peptide towards a polar surrounding.
      However, the peptide had a high surface activity (nmol/L) and was able to
      incorporate into lipid monolayers. Interaction was higher with charged
      phospholipids than with neutral ones. These results may have physiological
      significance in the mechanism of infection of host hepatic cells by HAV.

PMID- 11312536
TI  - Relationship between conformation of polysaccharides -in the dilute regime and
      their interaction with a phospholipid bilayer.
AB  - Interactions between polysaccharides and phospholipid bilayers have already been
      demonstrated in the literature but little is known about the influence of
      macromolecule conformations related to the solvent characteristics (pH, ions,
      ionic strength). In this study we have investigated the conformation of iono- and
      thermo-sensitive polysaccharides, iota- and kappa-carrageenans, and their
      interaction with a dimyristoylphosphatidylcholine (DMPC) model bilayer. The study
      was performed in two different media (NaCl 150 mmol/L, pH 6.5, and NaCl 300
      mmol/L, pH 6.5). In the first part, the iota- and kappa-carrageenan samples have
      been characterized by size exclusion chromatography (SEC) coupled with a multi
      angle laser light-scattering detector (MALLS). The SEC-MALLS results clearly show
      polysaccharide chain association at high ionic strength. In the second part, the
      polysaccharide-membrane interaction has been studied, using fluorescent probes
      embedded in the membrane. The thermotropic properties of the membrane were
      investigated by fluorescence depolarization of 1-(4-trimethylammonium-phenyl)-6
      phenyl-1,3,5-hexatriene (TMA-DPH). The membrane surface accessibility was
      evaluated by fluorescence quenching of 2-(9-anthroyloxy) stearic acid (2-AS).
      Whatever the ionic strength tested, the polysaccharide presence notably enhances
      the membrane fluidity below the T(m). This sign of an interaction in the polar
      level of the membrane is more marked at low NaCl concentration. In contrast, the
      liposomes bilayer accessibility is drastically lowered when increasing the ionic
      strength. This is induced by macromolecular chain adsorption on the liposome
      surface, enhanced by the polysaccharide chain association. An ionic strength
      enhancement induces a conformational modification of the polysaccharide chains
      which modifies their ability to interact with the bilayer.

PMID- 11312537
TI  - Inclusion complexes of nabumetone with beta-cyclodextrins: thermodynamics and
      molecular modelling studies. Influence of sodium perchlorate.
AB  - Fluorescence, (1)H-NMR and molecular mechanics have been used to study the
      inclusion complexes of nabumetone (4,6-methoxy-2-naphthyl-butan-2-one; NAB) with
      beta-cyclodextrin (beta-CD), randomly methylated-beta (M beta-CD) and
      hydroxypropyl-beta-cyclodextrins (HP beta-CD). The emission spectrum of NAB shows
      a maximum whose fluorescence intensity increases with the different beta-CDs
      growing concentrations. This phenomenon allows calculation of the stability
      constants at 15, 25, 37 and 45 degrees C. The thermodynamic parameters Delta H
      degrees and Delta S degrees for the inclusion process were obtained from the
      temperature dependence of the stability constants. Molecular mechanics
      calculations, together with proton NMR measurements, for the complex with beta-CD
      prove that the complex can be formed by penetration through any of the rims, with
      the naphthalene nucleus included and the substituents outside the cavity. The
      influence of NaClO(4) in the aforementioned complexes has been analysed by
      spectrofluorimetric measurements. It has been found that the stability constants
      for the complexes decrease with the salt concentration; the causes are discussed.

PMID- 11312538
TI  - Extraordinary hyperconjugation of the methyl group in the S(1) state of 8
      methylquinoline.
AB  - 8-Methylquinoline is unique among the monomethylquinolines in the red-shift it
      shows in the absorption band derived from the short axis polarized ((1)L(a) <--
      (1)A) electronic transition, relative to that in quinoline itself. The effect is
      even more pronounced in the 8-methylquinolinium cation, with the (1)L(a) band
      clearly emerging on the long-wavelength side of the (1)L(b) band, which is
      normally the longest wavelength absorption band in quinolines substituted with
      weakly interacting functional groups. The fluorescences of 8-methylquinoline and
      its conjugate acid show a pH dependence which is typical of N-heterocylic bases
      that undergo hydrolysis in the lowest excited singlet state. These observations
      are explained in terms of hyperconjugation in the lowest excited singlet state,
      with electronic charge being swept into the quinoline ring by coupling of the
      short-axis polarized transition of the ring system with the electrons of the
      methyl group in the 8-position of the ring.

PMID- 11312539
TI  - Membrane fusion induced by a lipopeptidic epitope from VP3 capside protein of
      hepatitis A virus.
AB  - Palmitoyl-VP3(110--121) (PVP3) is a synthetic lipopeptide derivative of a
      continuous epitope from the VP3 capsid protein of hepatitis A virus, and it is
      highly immunogenic in vivo. We have investigated the interaction of PVP3 with
      lipid model membranes of varying surface charge. Binding of PVP3 to anionic
      vesicles of PC/SM/PE/PS; (PC) 1-palmitoyl-2-oleoyl-phosphatidylcholine, (SM)
      sphingomyelin, (PE) 1,2-dipalmitoyl-phosphatidylethanolamine and (PS) L-alpha
      phosphatidyl-L-serine, a composition that mimics the lipid component of natural
      membranes, was determined by tryptophan fluorescence and quenching experiments.
      In addition, and given the anionic net charge of the lipopeptide, binding to
      zwitterionic (PC/SM/PE) and cationic PC/SM/PE/DOTAP (DOTAP) 1,2-dioleoyl-3
      trimethylammonium-propane mixtures was also determined. PVP3 binds to all three
      types of vesicles, but it adopts different forms depending on the electrical
      charge of the interface. This conclusion is supported by the insertion of PVP3
      into lipid monolayers of the same charges spread at the air-water interface. The
      bound lipopeptide has membrane-destabilizing effects in all three vesicle
      compositions, as demonstrated by leakage of vesicle contents, whereas lipid
      mixing only occurs in cationic liposomes. Our results provide useful information
      for the design of a liposomal system that promotes a direct delivery of the
      membrane-incorporated immunogen to the immunocompetent cells, potentially
      increasing the immune response from the host.

PMID- 11312540
TI  - Analysis of single-cell cultures by immunoaffinity capillary electrophoresis with
      laser-induced fluorescence detection.
AB  - Neuropeptide regulation of immunological activity is becoming an important issue
      in both basic and clinical sciences, necessitating the need for analysis to be
      performed at the single-cell level. A microsampling procedure has been developed
      for studying secretion of biologically important peptides from neuropeptide
      stimulated lymphocytes, based on microdialysis sampling coupled to immunoaffinity
      capillary electrophoresis (ICE), with laser-induced fluorescence (LIF) detection
      using a fibre-optic spectrometer and diode laser excitation. The system
      demonstrated a limit of detection in the high attomole (10(-18) mol/L) range with
      pure standards and was capable of monitoring secretion from a single cell over
      time. Using this system it was possible to differentiate the effects of four
      neuropeptides on both T and B cell release of regulatory cytokines. CD4(+)
      lymphocytes demonstrated a 7.5-fold increase in cytokine secretion over baseline
      following stimulation with substance P (SP) and calcitonin gene-related peptide
      (CGRP). B cells responded to CGRP and vasoactive intestinal peptide (VIP)
      stimulation (5.5-fold increase), but not to SP. These changes took place 12--20 h
      post-stimulation and, once the peak secretion had been reached, remained at that
      level for the duration of the experiment. This system demonstrates the ability to
      perform high sensitivity measurements on microsamples of biological fluids.

PMID- 11312541
TI  - Reporter cell lines are useful tools for monitoring biological activity of
      nuclear receptor ligands.
AB  - To characterize the specificity of synthetic compounds for nuclear receptors, we
      established stable cell lines expressing the luciferase gene and different wild
      type or chimaeric receptors. MCF-7 cells, which express the oestrogen receptor
      alpha (ER alpha), and HeLa cells, which do not express the oestrogen receptor,
      were transfected with a plasmid containing the luciferase gene downstream from a
      minimum promoter (beta-globin) and an oestrogen-responsive element, generating
      the MELN and the HELN cell lines, respectively. MELN cells enabled the detection
      of compounds that bind to the ER alpha or interfere with its pathway. HELN cells
      were used to establish stable transfectants expressing different nuclear
      receptors containing the DNA-binding domain of the oestrogen receptors. We thus
      established ER alpha or ER beta reporter cell lines by transfecting ER alpha or
      ER beta expression plasmids, and also retinoic acid receptor alpha, beta or gamma
      reporter cell lines by transfecting the chimaeric RAR gene, in which the DNA
      binding domain was replaced by the ER alpha DNA-binding domain.

PMID- 11312542
TI  - Electrogenerated chemiluminescence of luminol for oxidase-based fibre-optic
      biosensors.
AB  - The luminol electrochemiluminescence has been exploited for the development of
      several fibre-optic biosensors allowing the detection of hydrogen peroxide and of
      substrates of H(2)O(2)-producing oxidases. Electro-optical flow injection
      analysis of glucose, lactate, cholesterol and choline are thus described. To
      perform the experiments, a glassy carbon electrode was polarized at a fixed
      potential. Luminol was then electrochemically oxidized and could react in the
      presence of hydrogen peroxide to produce light. Several parameters had to be
      optimized to obtain reliable optical biosensors. An optimum applied potential of
      +425 mV between the glassy carbon electrode and the platinum pseudo-reference
      electrode was determined, allowing the best signal: noise ratio to be obtained.
      It was also necessary to optimize the experimental conditions for the
      immobilization of the different oxidases involved (preactivated membranes,
      chemically activated collagen membranes, photopolymerized matrix). For each
      biosensor developed, the optimum reaction conditions have been studied: buffer
      composition, pH, temperature, flow rate and luminol concentration. Under optimal
      conditions, the detection limits (S/N = 3) were 30 pmol, 60 pmol, 0.6 nmol and 10
      pmol for lactate, glucose, cholesterol and choline, respectively. The
      miniaturization of electrochemiluminescence-based biosensors has been realized
      using screen-printed electrodes instead of a glassy carbon macroelectrode, with
      choline oxidase as a model H(2)O(2)-generating oxidase.

PMID- 11312543
TI  - Application of an enhanced luminol chemiluminescence reaction using 4-[4,5-di(2
      pyridyl)-1H-imidazol-2-yl]phenylboronic acid to photographic detection of
      horseradish peroxidase on a membrane.
AB  - Photographic detection of horseradish peroxidase (HRP) on a membrane by the
      luminol-hydrogen peroxide-HRP chemiluminescence reaction using 4-[4,5-di(2
      pyridyl)-1H-imidazol-2-yl]phenylboronic acid (DPPA) as an enhancer is described.
      The method is based on the long-lived chemiluminescence emission obtained by
      using DPPA. Under the optimum conditions, as little as 0.10 ng (ca. 2.3 fmol) and
      0.20 ng (ca. 4.6 fmol) per spot of HRP on a membrane were detected as visible
      spots with exposure time of 60 and 10 min, respectively, by using an instant
      photographic film and a camera luminometer. The proposed method was highly
      sensitive and was successfully applied to the detection of HRP conjugates as an
      alternative to the colorimetric method using a chromogenic substrate in a
      commercially available assay kit of Western blotting.

PMID- 11312544
TI  - Importance of the ionization states of m-THPC for its HPLC fluorescence
      detection.
AB  - An original, rapid and sensitive high-performance liquid chromatographic (HPLC)
      method has been developed for the detection of 5, 10, 15, 20 tetra-meso
      hydroxyphenylchlorine (m-THPC), a photosensitizer used in the photodynamic
      therapy (PDT) of cancers. Chromatographic separation was carried out on a C(8)
      Zorbax column (80 x 4 mm, 5 microm). The mobile phase was an ethanol/aqueous
      sulphuric acid, pH 2.0 (65/35 v/v), in an isocratic mode yielding to rapid
      analysis (3.1 min) with narrow peaks. As the fluorescence intensity was found to
      be highly pH-dependent and to increase with pH values, a post-column device prior
      to the fluorescence detection (lambda(exc) = 423 nm, lambda(em) = 650 nm) was
      used to allow the addition of a 0.05 mol/L Na(2)HPO(4) solution to the mobile
      phase. Compared to standard conditions, a 300% increase of the fluorescence
      intensity was obtained for optimized operating conditions using experimental
      design. The validation of this analytical method showed that the response
      function was linear for concentrations up to 1000 microg/L (1.47 x 10(-6) mol/L)
      with a detection limit of 188 pg (S/N = 3).

PMID- 11312545
TI  - A fibre-optic calcium ion sensor using a calcein derivative.
AB  - This paper describes the development of a new fibre-optic calcium ion sensor
      based on the immobilization of the calcein derivative, calcein acrylamide (CA)
      onto an optical fibre. The method involves the covalent attachment of CA in a
      polymer which itself is covalently bonded to an optical fibre. The fluorescence
      of CA is pH-sensitive in the region 4--12 and also increases as a function of
      Ca(2+) concentration at pH > 12. Typically, the indicator is sensitive to Ca(2+)
      in the concentration range 0--20 micromol/L, with a linear region occurring when
      the concentration of calcium is equal to or below that of CA. The binding ratio
      of Ca(2+) to CA in the linear calibration region is 1:1 and beyond the linear
      region is 2:1. The calcium-sensitive polymer is prepared using photo-initiated
      polymerization of a stock solution containing CA, monomer, a crosslinker and a
      photo-initiator. The monomer units used were acrylamide and acrylamide doped with
      MAPTAC. The fluorescence characteristics of bound CA in acrylamide are similar to
      that of CA in solution. However, the cationic nature of the polymer doped with
      MAPTAC allows analysis of Ca(2+) to be carried out in pH 8.5 solution. The Ca(2+)
      sensing range of the sensor is typically 0--12 micromol/L.

PMID- 11312546
TI  - Chemiluminescent acridan phosphate labelling compounds for detection in gels.
AB  - We have developed a chemiluminescent acridan phosphate labelling compound which
      produces a flash of light upon chemical triggering. Sequential treatment of the
      label with acid and a strong base, one of which contains a peroxide, initiates
      light emission as a rapid flash lasting 1--2 s. Labelling of analytes with these
      compounds permits their direct detection in a non-enzymatic assay format.
      Representative compounds have been linked to BSA as a model protein analyte and
      detected by chemiluminescence assay. Light intensity correlated with the amount
      of BSA over six orders of magnitude, permitting the detection of 50 amol of
      protein in solution. We have also demonstrated for the first time that labelled
      proteins can be separated by electrophoresis without destruction of the label and
      that chemiluminescence can be produced and detected directly in the gel. The
      ease, speed and sensitivity of detection by this new method should enable the
      development of simpler assays for a wide variety of analytes.

PMID- 11312547
TI  - Applications of biochemiluminescence to HACCP.
AB  - The hazard analysis critical control point) (HACCP) system is set up with the aim
      of ensuring the harmlessness of food along the process chain, from the producer
      to the ultimate consumer. To set up this system, it is necessary to perform an
      analysis to identify the dangers and the critical points of the process in real
      time. Living organisms are detected on the principle of measurement of cellular
      energy in the form of adenosine triphosphate (ATP), which is produced by all
      living cells and of particularly by microorganisms. The principle of the
      bioluminescence of firefly luciferase is applied, whereby a reduced form of
      luciferin, together with a molecule of oxygen and ATP in the presence of the
      enzyme luciferase, produces a reaction in which oxyluciferine is released,
      together with AMP. This is accompanied by a simultaneous release of photons,
      which are then quantified. The emission spectra recorded with the firefly
      luciferin/luciferase system is obtained with absolute sensitivity. The method of
      ATP assays here proposed is adapted for measuring the total content of different
      adenylates in the cell, i.e. the adenylate pool. ATP concentration is then
      measured through bioluminescence, i.e. the light is measured by a photomultiplier
      tube detector and the signal is converted to relative light units (RLU). Thus,
      RLU have a relationship with the amount of ATP present in the sample, which is
      not the case with traditional methods. Adequate levels of sensitivity are
      calculated with appropriate controls and the readings are translated into a
      statistical designation of positive or negative result. There are numerous
      illustrations of HACCP applications using biochemiluminescence (BCL) techniques
      as detection technology in food industry production lines and in control of
      critical points in real time in industrial applications.

PMID- 11312548
TI  - Intrinsic fluorescence of enzymes and fluorescence of chemically modified enzymes
      for analytical purposes: a review.
AB  - In recent years our research group has developed new alternatives for
      fluorescence enzymatic determinations. First, we observed that the intrinsic
      fluorescence of enzymes changes during enzymatic reactions, proportionally to the
      substrate concentration, avoiding the combination of the enzymatic reaction with
      a fluorophore-involving reaction. The main disadvantage of this method is that
      the excitation and emission wavelengths of the enzymes are in the UV region of
      the spectrum. An alternative to overcome this problem consisted of covalently
      bonding the enzyme to a fluorophore. In this paper, an overview is given of all
      of the applications and future developments on both types of alternatives that we
      have developed. Apart from the analytical characteristics of the methods, we have
      also reviewed all of the information about mathematical models we have elaborated
      to date.

PMID- 11312550
TI  - Support ventilation versus conventional oxygen.

PMID- 11312551
TI  - Getting fit online.

PMID- 11312552
TI  - Retinal integration of grafts of brain-derived precursor cell lines implanted
      subretinally into adult, normal rats.
AB  - The ability of in vitro-expanded neural precursor cells or cell lines to
      differentiate following transplantation has significant implications for current
      research on central nervous system repair. Recently, interest has been focussed
      on grafts of such neural precursors implanted also into the eye or retina. Here,
      we demonstrate with a non-traumatizing subretinal transplantation method, that
      grafts of the two immortalized brain-derived cell lines C 17-2 (from postnatal
      mouse cerebellum) and RN33B (from the embryonic rat medullary raphe) survive for
      at least up to four weeks, after implantation into the adult normal rat retina.
      For both cell lines, implanted cells gradually integrate into all major retinal
      cell layers, including the retinal pigment epithelium, and judged by the
      morphology differentiate into both glial- and neuron-like cells, as shown by
      thymidine autoradiography, mouse-specific in situ hybridization, and using
      immunohistochemistry to detect the reporter gene LacZ. Our results suggest that
      these and other similar neural cell lines could be very useful in the continuous
      experiments in models of retinal disorders to further assess both the cell
      replacement and ex vivo gene therapy approaches.

PMID- 11312553
TI  - Impairment of the blood-nerve and blood-brain barriers in apolipoprotein e
      knockout mice.
AB  - Apolipoprotein E (apoE) is well characterized as a plasma lipoprotein involved in
      lipid and cholesterol metabolism. Recent studies implicating apoE in Alzheimer's
      disease and successful recovery from neurological injury have stimulated much
      interest in the functions of apoE within the brain. To explore the functions of
      apoE within the nervous system, we examined apoE knockout (KO) mice. Previously,
      we showed that apoE KO mice have a delayed response to noxious thermal stimuli
      associated with a loss and abnormal morphology of unmyelinated fibers in the
      sciatic nerve. From these data, we hypothesized that apoE KO mice could have an
      impaired blood-nerve barrier (BNB). In this report, we demonstrate functionally
      impaired blood-nerve and blood-brain barriers (BBB) in apoE KO mice using
      immunofluorescent detection of serum protein leakage into nervous tissue as a
      diagnostic for decreased BNB and BBB integrity. Extensive extravasation of serum
      immunoglobulin G (IgG) is detected in the sciatic nerve, spinal cord, and
      cerebellum of apoE KO but not WT mice. In a subpopulation of apoE KO mice, IgG
      also extravasates into discrete cortical and subcortical locations, including
      hippocampus. Loss of BBB integrity was additionally confirmed by the ability of
      exogenously supplied Evans blue dye to penetrate the BBB and to colocalize with
      IgG immunoreactivity in CNS tissue. These observations support a role for apoE in
      maintaining the integrity of the BNB/BBB and suggest a novel relationship between
      apoE and neural injury.

PMID- 11312554
TI  - Diminished survival of mesencephalic dopamine neurons grafted into aged hosts
      occurs during the immediate postgrafting interval.
AB  - The survival rate of dopamine (DA) neurons in mesencephalic grafts to young adult
      rats is poor, estimated at 5-20%, and even poorer in grafts to the aged striatum.
      Grafted cells die in young adult rats during the first 4 days after implantation.
      The present study was undertaken to determine whether the decreased survival of
      DA neurons in grafts to aged rats is (1) due to additional cell death during the
      immediate postgrafting interval or (2) due to protracted cell loss during longer
      postgrafting intervals. We compared survival rates of tyrosine hydroxylase
      immunoreactive (THir) neurons in cell suspension grafts to young adult (3 months)
      and aged (24 months) male Fischer 344 rats at 4 days and 2 weeks after
      transplantation. At 4 days after grafting, mesencephalic grafts within the aged
      rat striatum contain approximately 25% of the number of THir neurons in the same
      mesencephalic cell suspension grafted to young adult rats. This corroborates the
      decreased survival of grafted DA neurons we have demonstrated previously at 10
      weeks postgrafting. THir neurons in grafts to the intact striatum possessed a
      significantly shorter "long axis" than their counterparts on the lesioned side.
      No significant differences in the number of apoptotic nuclear profiles or total
      alkaline phosphatase staining between mesencephalic grafts to young and aged rats
      were detectable at 4 days postgrafting. In summary, the present study indicates
      that the exaggerated cell death of grafted DA neurons that occurs following
      implantation to the aged striatum occurs during the immediate postgrafting
      interval, timing identical to that documented for young adult hosts.

PMID- 11312555
TI  - Regeneration and recovery of the hearing function of the central auditory pathway
      by transplants of embryonic brain tissue in adult rats.
AB  - The present study is the first report of successful regeneration and recovery of
      hearing function of the central auditory pathway after transection in the adult
      rat. The ventral cochlear tract in the brain stem to pons was transected on one
      side in adult rats. Tissue from embryos (E14 to E16) was used to cover the lesion
      site. In 30% of the rats examined, the axons regrew beyond the transected site
      and regenerated into the denervated side and terminated at the normal targets.
      The hearing function of rats was elucidated by recording the auditory brain stem
      response (ABR). Rats with successful regeneration showed nearly normal ABR. In
      rats receiving simple transection without covering embryonic tissue, there was no
      regeneration and hearing function did not recover. Thus, the present findings
      contradict the widely held view that the adult mammalian central auditory system
      cannot be restored following damage.

PMID- 11312556
TI  - Sonic hedgehog and FGF8: inadequate signals for the differentiation of a dopamine
      phenotype in mouse and human neurons in culture.
AB  - Embryonic mouse striatal neurons and human neurons derived from the NT2/hNT stem
      cell line can be induced, in culture, to express the dopaminergic (DA)
      biosynthetic enzyme tyrosine hydroxylase (TH). The novel expression of TH in
      these cells is signaled by the synergistic interaction of factors present in the
      media, such as fibroblast growth factor 1 (FGF1) and one of several possible
      coactivators [DA, phorbol 12-myristate 13-acetate (TPA), isobutylmethylxanthine
      (IBMX), or forskolin]. Similarly, in vivo, it has recently been reported that the
      expression of TH in the developing midbrain is mediated by the synergy of FGF8
      and the patterning molecule sonic hedgehog (Shh). In the present study, we
      examined whether the putative in vivo DA differentiation factors can similarly
      signal TH in our in vitro cell systems. We found that FGF8 and Shh induced TH
      expression in fewer than 2% of NT2/hNT cells and less than 5% of striatal
      neurons. The latter could be amplified to as much as 30% by increasing the
      concentration of growth factor 10-fold or by the addition of other competent
      coactivators (IBMX/forskolin, TPA, and DA). Additivity/inhibitor experiments
      indicated that FGF8 worked through traditional tyrosine kinase-initiated MAP/MEK
      signaling pathways. However, the Shh signal transduction cascade remained
      unclear. These data suggest that cues effective in vivo may be less successful in
      promoting the differentiation of a DA phenotype in mouse and human neurons in
      culture. Thus, our ability to generate DA neurons from different cell lines, for
      use in the treatment of Parkinson's disease, will depend on the identification of
      appropriate differentiation signals for each cell type under investigation.

PMID- 11312557
TI  - Coupling of cAMP/PKA and MAPK signaling in neuronal cells is dependent on
      developmental stage.
AB  - Neurite formation, an essential feature of neuronal development, is believed to
      involve participation of the ras-mitogen-activated protein kinase (MAPK) and cAMP
      dependent protein kinase A (cAMP/PKA)-mediated signaling pathways. These pathways
      have been studied extensively in the rat pheochromocytoma cell line PC12, and
      current hypotheses suggest a single effector mechanism resulting from the
      convergence of cAMP/PKA and MAPK signaling. However, based on observations using
      a central neuronal progenitor cell line, AS583-8, there also exists evidence that
      the two signaling pathways may act independently resulting in neurites with
      differing dynamic features. In the present study, the upstream components of
      cAMP/PKA signaling were examined in AS583-8 cells as well as possible
      interactions with the MAPK pathway. We found that activation of PKA is both
      necessary and sufficient for the elaboration of rapidly forming processes,
      typical of the cAMP response. In addition, blockade of the MAPK pathway has no
      effect on the cAMP response, suggesting that activation of the cAMP/PKA pathway
      can stimulate neurite formation independent of the MAPK pathway. In order to
      evaluate which cell line model, PC12 vs AS583-8, best reflects the signaling
      features of developing central neurons, we examined interactions between cAMP/PKA
      and MAPK signaling in primary neuronal cultures from several brain regions. In
      immature cultures (1-day-old), at a point where the initiation of neurite
      formation is maximal, no interaction was observed. In more mature cultures (7
      days old), where synaptic contacts have been established, we found a weak but
      reproducible activation of MAPK following stimulation of the cAMP/PKA pathway.
      These results suggest that cAMP/PKA and MAPK signaling act independently at the
      initiation of neuritogenesis but become coupled during later stages of neuronal
      development. Therefore, the interaction of the two pathways may be cell stage
      (younger vs older) specific and may participate in cellular functions that take
      place after initial neurite formation.

PMID- 11312558
TI  - MRI analysis of the changes in apparent water diffusion coefficient, T(2)
      relaxation time, and cerebral blood flow and volume in the temporal evolution of
      cerebral infarction following permanent middle cerebral artery occlusion in rats.
AB  - Detailed knowledge of similarities and differences between animal models and
      human stroke is decisive for selecting clinically effective drugs based on
      efficacy data obtained preclinically. Differences in the temporal evolution of
      stroke pathologies between animal models and man have been reported. In view of
      the importance of this issue for the development of neuroprotective treatments,
      the temporal evolution of stroke pathologies in the rat permanent middle cerebral
      artery occlusion (pMCAO) model has been evaluated with magnetic resonance imaging
      modalities under experimental conditions matching as close as possible those used
      in humans. Changes in the ipsilateral and contralateral cortex and striatum of
      cerebral blood flow (CBF) and volume (CBV), apparent diffusion coefficient (ADC),
      and spin-spin relaxation time (T(2)), as well as total cortical and striatal
      infarct volumes, calculated from CBF, ADC, and T(2) maps, were determined
      starting 1 h up to 216 h post-pMCAO. The temporal evolution of the MRI parameters
      in this rat model was similar to that observed in humans. In particular, the ADC
      values were decreased for more than 3 days and returned back to baseline between
      4 to 8 days, to increase by day 9 only. Thus the stroke pathology in this rat
      model develops at a similar pace as in stroke patients arguing against a
      fundamental difference in the mechanisms involved. The infarct volumes however
      develop differently in this rat model as they invariably increase over the first
      48 h, while in humans the evolution of infarct volume is slower and more
      heterogeneous.

PMID- 11312559
TI  - Therapeutic efficacy of G207 in a novel peripheral nerve sheath tumor model.
AB  - Nerve involvement poses a significant obstacle for the management of peripheral
      nervous system tumors, and nerve injury provides a frequent source of
      postoperative morbidity. The lack of suitable animal models for peripheral nerve
      tumors has impeded the development of alternative nerve-sparing therapies. To
      evaluate the effect of a multimutated replication-competent herpes simplex virus
      (G207) on the growth of peripheral nerve tumors and on nerve function, we
      developed a novel peripheral nerve sheath tumor model. Human neuroblastoma
      derived cells injected into murine sciatic nerve consistently caused tumor
      development within the nerve sheath after 2 weeks followed by increasingly severe
      impairment of nerve function. Tumor treatment by a single intratumoral injection
      of G207 resulted in significant reduction of functional impairment, inhibition of
      tumor growth and prolonged survival. Direct injection of G207 viral particles
      into the healthy nerve sheath caused no obvious neurologic sequelae, whereas
      injections of wild-type virus resulted in uniform lethality. The results indicate
      that viral therapy might be considered as a safe alternative to surgical removal
      of tumors with peripheral nerve involvement.

PMID- 11312560
TI  - Clostridium perfringens prototoxin-induced alteration of endothelial barrier
      antigen (EBA) immunoreactivity at the blood-brain barrier (BBB).
AB  - It has been reported that the severe cerebral edema produced in experimental
      animals by Clostridium perfringens (Cl p) type D epsilon toxin can be prevented
      by prior treatment with its precursor prototoxin due to competitive binding to
      endothelial cells (ECs) at the blood-brain barrier (BBB). In this study we
      investigate the effects of the prototoxin on the BBB, without added toxin. The
      integrity of the BBB was assessed by its ability to prevent leakage of endogenous
      albumin. ECs at the BBB were studied by immunocytochemistry for any alteration in
      the endothelial barrier antigen (EBA), a molecular marker for the intact BBB.
      Immunocytochemistry showed rapid but mild opening of the BBB to endogenous
      albumin. Light and electron immunocytochemistry showed qualitative and
      quantitative reduction in EBA immunoreactivity, with a spectrum of changes at
      time intervals from 1 h to 14 days post-prototoxin injection. Some vessels with
      ultrastructural changes and widening of the perivascular space retained EBA
      immunoreactivity. Many vessels showed partial or complete loss of EBA staining
      with minimal widening of the perivascular space and edema. Recovery of EBA
      expression was still incomplete at 14 days postinjection. This is the first
      report to show endothelial cell damage, mild reversible cerebral edema, and
      alteration in BBB markers following administration of Cl p prototoxin. This model
      of mild brain edema may be useful for BBB studies.

PMID- 11312561
TI  - Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects
      dopaminergic terminals from degeneration.
AB  - Previously, we observed that injection of an adenoviral (Ad) vector expressing
      glial cell line-derived neurotrophic factor (GDNF) into the striatum, but not the
      substantia nigra (SN), prior to a partial 6-OHDA lesion protects dopaminergic
      (DA) neuronal function and prevents the development of behavioral impairment in
      the aged rat. This suggests that striatal injection of AdGDNF maintains
      nigrostriatal function either by protecting DA terminals or by stimulating axonal
      sprouting to the denervated striatum. To distinguish between these possible
      mechanisms, the present study examines the effect of GDNF gene delivery on
      molecular markers of DA terminals and neuronal sprouting in the aged (20 month)
      rat brain. AdGDNF or a control vector coding for beta-galactosidase (AdLacZ) was
      injected unilaterally into either the striatum or the SN. One week later, rats
      received a unilateral intrastriatal injection of 6-OHDA on the side of vector
      injection. Two weeks postlesion, rats injected with AdGDNF into either the
      striatum or the SN exhibited a reduction in the area of striatal denervation and
      increased binding of the DA transporter ligand [(125)I]IPCIT in the lesioned
      striatum compared to control animals. Furthermore, injections of AdGDNF into the
      striatum, but not the SN, increased levels of tyrosine hydroxylase mRNA in
      lesioned DA neurons in the SN and prevented the development of amphetamine
      induced rotational asymmetry. In contrast, the level of T1 alpha-tubulin mRNA, a
      marker of neuronal sprouting, was not increased in lesioned DA neurons in the SN
      following injection of AdGDNF either into the striatum or into the SN. These
      results suggest that GDNF gene delivery prior to a partial lesion ameliorates
      damage caused by 6-OHDA in aged rats by inhibiting the degeneration of DA
      terminals rather than by inducing sprouting of nigrostriatal axons.

PMID- 11312562
TI  - Enhanced excitability induced by ionizing radiation in the kindled rat.
AB  - Evidence derived from both clinical and experimental investigations has suggested
      an influence of ionizing radiation on focal epileptogenicity. To better
      characterize this influence we applied focal ionizing radiation to a kindled
      epileptic focus in the rat amygdala. The right and left basolateral amygdala and
      right frontal cortex were implanted with concentric bipolar electrodes. Rats were
      kindled through a minimum of 10 stage 5 seizures by afterdischarge-threshold
      electrostimulation of the left amygdala, after which generalized seizure
      thresholds were determined prior to irradiation. The left amygdala was exposed to
      single-fraction central-axis doses of either 18 or 25 Gy using a beam-collimated
      (60)Co source (1.25 MeV). Generalized seizure thresholds were then redetermined
      at weekly intervals for 10 weeks and at monthly intervals for an additional 3
      months. We observed no significant changes in seizure threshold during the
      postirradiation interval; however, we did observe persistent changes in seizure
      dynamics manifesting within the first week postirradiation. These consisted of an
      increased tendency for seizure activity to propagate into brain stem circuits
      during the primary ictus (i.e., "running fits") and an increased tendency for
      secondary convulsions to emerge postictally. These effects involving seizure
      dynamics have not been reported previously and appear to represent a radiation
      induced disinhibition of one or more neural circuits. The disparity between these
      effects and earlier reports of seizure-suppressive effects resulting from
      analogous radiation exposures is discussed in relation to kindling and status
      epilepticus-induced pathogenesis within the hippocampus.

PMID- 11312563
TI  - Alternative splicing of amino-terminal Tau mRNA in rat spinal cord during
      development and following axonal injury.
AB  - Tau is a family of microtubule-associated phosphoproteins in which isoform
      variation is produced by alternative splicing of a single gene and
      posttranslational modifications. Tau isoforms that include exon 10 are
      overexpressed in frontotemporal dementia and progressive supranuclear palsy.
      Therefore, we examined the expression of tau mRNA splice variants during axonal
      regeneration and abortive regeneration. Previous work in our laboratory
      demonstrated that expression of exon 10 tau isoforms during regeneration and
      abortive regeneration was altered and partially recapitulated the developmental
      patterns of tau isoform expression. Using RT-PCR, we examined the alternative
      splicing of exons 2 and 3 in tau during early postnatal development and
      regeneration in the rat spinal cord. The levels of tau lacking exons 2 and 3 were
      high on the day of birth and rapidly declined. Conversely, tau isoforms
      containing exon 2 or exons 2 and 3 first appeared at low levels and steadily
      increased. During axonal regeneration, the levels of all three tau mRNA isoforms
      were significantly lower 7 days after injury. In a model of abortive
      regeneration, all of the tau isoforms were elevated 14 and 42 days postinjury.
      The relative levels of exon 2 and 3 tau splice variants were not altered during
      regeneration or abortive regeneration as occurred during development. These
      results suggest that tau isoform expression following neuronal injury does not
      recapitulate the developmental pattern and is not independently regulated as in
      development. Our previous results together with these data suggest that
      alterations in tau mRNA isoform expression that occur in neurodegeneration are
      not secondary to axonal injury but may be a more primary event underlying
      cytoskeletal derangement.

PMID- 11312564
TI  - Graft location affects functional rescue following RPE cell transplantation in
      the RCS rat.
AB  - Photoreceptor (PRC) rescue in the dystrophic Royal College of Surgeons (RCS) rat
      has been well documented following a variety of interventions. Although the
      dystrophic process is asymmetric with respect to the horizontal meridian, little
      attention has been paid to the effect of topographic position on treatment
      outcome. In this study, RPE cells from adult congenic nondystrophic animals were
      injected into the subretinal space of 1-month-old dystrophic RCS rats in either
      the dorsal or the ventral equatorial region. Animals were followed longitudinally
      during the degenerative process using the pupillary light reflex (PLR). The
      parameter of the PLR most sensitive to PRC rescue is latency at low light levels.
      At 3 months of age this parameter showed statistically better performance (ANOVA,
      P = 0.016) for eyes with grafts placed dorsally compared to those placed
      ventrally or untreated controls. There was no treatment effect on amplitude. By 6
      months of age the dorsal/ventral disparity in latency was less apparent and
      amplitude remained equivalent across groups. Late analysis of retinal whole
      mounts using RT-97 fluorescent labeling showed extensive irregularities in
      ventral axonal morphology in all treatment groups. These results indicate that
      functional rescue of the RCS retina is significantly influenced by the local
      degenerative timetable. The role of initial local conditions on treatment outcome
      is worthy of consideration in other models of neuroprotection.

PMID- 11312565
TI  - Coadministration of (-)-OSU6162 with l-DOPA normalizes preproenkephalin mRNA
      expression in the sensorimotor striatum of primates with unilateral 6-OHDA
      lesions.
AB  - The substituted phenylpiperidine (-)-OSU6162 is a novel modulator of the
      dopaminergic systems with low affinity for dopamine D(2) receptors and potent
      normalizing effects on l-DOPA-induced dyskinesias. We studied the effects of
      coadministration of (-)-OSU6162 with l-DOPA on the regulation of striatal
      preproenkephalin (PPE) and prodynorphin (PDyn) mRNA expression in the primate
      brain by in situ hybridization histochemistry. Common marmoset monkeys sustaining
      unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received l
      DOPA/carbidopa, l-DOPA/carbidopa plus (-)-OSU6162, or vehicle over 14 days. In
      vehicle-treated animals, PPE mRNA levels were markedly increased in the
      sensorimotor territory of the lesioned striatum. By contrast, a rather uniform
      lesion-induced reduction of PDyn mRNA levels was found in the vehicle group.
      Subchronic l-DOPA treatment induced a further increase in PPE mRNA expression in
      a number of sensorimotor and associative subregions of the denervated striatum.
      Coadministration of (-)-OSU6162 with l-DOPA partially reversed the lesion- and l
      DOPA-induced elevation of PPE expression and, by affecting PPE mRNA expression
      differentially on the intact and lesioned striatum, markedly reduced the side-to
      side difference in PPE mRNA expression. The effects on PPE mRNA expression were
      apparent throughout the rostrocaudal extent of the putamen and the dorsal
      portions of the caudate nucleus. l-DOPA treatment resulted in an enhancement in
      PDyn mRNA expression in all functional compartments of the striatum.
      Coadministration of (-)-OSU6162 had no apparent influence on these l-DOPA-induced
      changes in PDyn mRNA expression. The present results suggest that (-)-OSU6162
      acts primarily by modifying striatal output via the indirect pathway.

PMID- 11312566
TI  - Regeneration of entorhinal fibers in mouse slice cultures is age dependent and
      can be stimulated by NT-4, GDNF, and modulators of G-proteins and protein kinase
      C.
AB  - Axonal regeneration after lesions is normally not possible in the mature central
      nervous system, but occurs in the embryonic and neonatal nervous system. Slice
      cultures offer a convenient experimental system to study the decline of axonal
      regeneration with increasing maturation of central nervous system tissue. We have
      used mouse entorhinohippocampal slice cultures to assess regeneration of
      entorhinal fibers after mechanical lesions in vitro. We found that entorhinal
      axons regenerate well in cultures derived from postnatal days 5-7 mouse pups when
      the lesion is made at the second and fourth days in vitro (DIV 2 and DIV 4). Only
      little regenerative outgrowth is seen after lesions made at DIV 6 and DIV 10.
      This indicates that a maturation of the cultures occurs within a short time
      period in vitro resulting in a loss of the regenerative potential. We have used
      this system to screen for neurotrophic factors and pharmacological compounds that
      may promote axonal regeneration. Treatments were added to the cultures 1 day
      before the lesion was made. We found that most added factors did not promote
      regeneration. Only treatment with the neurotrophic factors NT-4 and GDNF
      stimulated regeneration in cultures where normally little regeneration is found.
      A similar improvement of regeneration was found after treatment with pertussis
      toxin, an inhibitor of G(i)-proteins, and with GF109203X, an inhibitor of protein
      kinase C. These substances may promote regeneration by interfering with
      intracellular signaling pathways activated by outgrowth inhibitors. Our findings
      indicate that the application of neurotrophic factors and the modulation of
      intracellular signal transduction pathways could be useful strategies to enhance
      axonal regeneration in a complex microenvironment.

PMID- 11312567
TI  - Interaction between D2 dopaminergic and glutamatergic excitatory influences on
      lower urinary tract function in normal and cerebral-infarcted rats.
AB  - Previous studies showed that bladder hyperactivity after cerebral infarction in
      Sprague-Dawley (SD) rats was mediated in part by D2 dopaminergic and NMDA
      glutamatergic mechanisms. In the present experiments, the interaction between
      dopaminergic and glutamatergic excitatory mechanisms in the control of bladder
      and external urethral sphincter (EUS) reflexes was investigated in urethane
      anesthetized sham-operated (SO) and cerebral-infarcted (CI) SD rats. Occlusion of
      the left middle cerebral artery or a sham operation was performed under halothane
      anesthesia. Two hours after either of the two procedures, rats were anesthetized
      with urethane. Dizocilpine, an N-methyl-d-aspartate (NMDA) glutamatergic
      antagonist, was administered intravenously in doses of 0.3 or 3 mg/kg to CI rats
      and 3 mg/kg to SO rats. These doses completely inhibited bladder and EUS
      activity. The effects of apomorphine (a dopamine agonist with greater efficacy at
      D2 than D1 receptors) or quinpirole (a selective D2 dopamine receptor agonist)
      were examined on the dizocilpine-induced depression of bladder contractions and
      EUS EMG activity. Apomorphine did not antagonize the dizocilpine depression of
      EUS activity, but it did reestablish the micturition reflex after dizocilpine
      blockade and did increase the amplitude of bladder contractions and voided volume
      in a dose-dependent manner (0.0001-10 mg/kg, iv), in both CI rats and SO rats
      pretreated with dizocilpine. There were no differences between SO rats and CI
      rats in the apomorphine responses in rats pretreated with doses of 0.3 or 3 mg/kg
      dizocilpine. A larger dose of dizocilpine (10 mg/kg) did not affect the bladder
      contractions after apomorphine administration. Quinpirole (0.001-1 mg/kg, iv)
      also partially reversed the dizocilpine depression of bladder activity in SO and
      CI rats. These results indicate that NMDA glutamatergic and D2 dopaminergic
      mechanisms exert independent excitatory influences on bladder activity in both SO
      and CI rats. D2 dopamine receptor agonists can reverse the effect of NMDA
      receptor blockade on bladder activity but were ineffective in reversing the block
      of sphincter activity.

PMID- 11312568
TI  - Activation of serotonergic pathways from the midbrain raphe system to the
      subfornical organ by hemorrhage in the rat.
AB  - The role of serotonergic neural pathways from the midbrain raphe nuclei to the
      subfornical organ (SFO) in the central regulation of cardiovascular function and
      body fluid balance was investigated in adult male rats under urethane anesthesia.
      Eleven neurons in the dorsal raphe nucleus (DR) were antidromically activated by
      electrical stimulation of the SFO. Of these neurons, 6 displayed an excitatory
      response following hemorrhage (10 ml/kg bwt) while the remaining 5 neurons were
      unresponsive. Ninety-four neurons in the SFO were tested for a response to
      electrical stimulation of the DR or hemorrhage. Electrical stimulation of the DR
      caused orthodromic excitation (19%) or inhibition (5%) of the activity of SFO
      neurons. In 14 of 18 SFO neurons that displayed the excitation to the stimulation
      of the DR, hemorrhage (30 to 50 mm Hg suppression in mean arterial pressure)
      produced an increase of their discharge, while the stimulus was without effect in
      the remaining neurons responsive to the stimulation of the DR. The effects of
      hemorrhage on serotonin (5-HT) release in the region of the SFO were examined
      using intracerebral microdialysis techniques. Hemorrhage significantly increased
      5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the
      region of the SFO. The present data suggest that the serotonergic pathways from
      the DR to the SFO may relay activation of the peripheral baroreceptors to SFO
      neurons which result in enhanced excitability, indicating the involvement of the
      pathways in the regulation of cardiovascular function.

PMID- 11312569
TI  - Dopamine cell degeneration induced by intraventricular administration of 6
      hydroxydopamine in the rat: similarities with cell loss in parkinson's disease.
AB  - In an attempt to find a convenient rat model to study cell vulnerability in
      Parkinson's disease, we have investigated the cell-loss profile in different
      midbrain dopaminergic nuclei and subnuclei of rats injected with 6
      hydroxydopamine (6-OHDA) in the third ventricle. Following administration of
      different doses (5-1000 microgram) of 6-OHDA, motor behavior was evaluated and
      tyrosine hydroxylase-immunostained neurons were counted in the A8 group and
      different subdivisions of A9 and A10 groups. Animals developed hypokinesia,
      repetitive chewing movements, and catalepsia. Signs of cell degeneration were
      evident from the first day after injection, reaching the definitive pattern at
      the end of the first week. There was a similar degeneration in both brain sides,
      the A9 group showing the highest degree of cell-loss, followed by A8 and A10
      groups. In the A9 group, the degeneration mostly affected those subgroups located
      in its ventral, lateral, and posterior regions. In the A10 group the degeneration
      mainly affected the parabrachial pigmented nucleus, the paranigral nucleus and
      the ventral tegmental area. This topographic pattern of degeneration is very
      similar to that previously described in Parkinson's disease, suggesting that this
      model may be a useful tool in the study of the cell vulnerability mechanisms in
      this neurodegenerative disorder. In addition, our results also showed that small
      dopaminergic neurons are more resistant to degeneration than the large ones. In
      some DA subgroups, the cells that contained calbindin but not calretinin were
      less vulnerable to the neurotoxic effect of 6-OHDA.

PMID- 11312570
TI  - The effect of unilateral sympathectomy and cavity preparation on peptidergic
      nerves and immune cells in rat dental pulp.
AB  - Recent evidence suggests interactions between primary afferent nociceptors and
      postganglionic sympathetic efferents in the pathogenesis of inflammation. The
      effect of unilateral removal of the superior cervical ganglion on the innervation
      pattern of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide
      (CGRP), substance P (SP), and neuropeptide Y (NPY), as well as the occurrence of
      immune cells in the injured and uninjured rat molar pulp, was investigated. Light
      microscopic immunocytochemistry demonstrated that the molar pulps contralateral
      to the sympathectomy contained a NPY-IR nerve fiber network more dense and
      heavily stained than unoperated control rats. The NPY-IR fibers showed, however,
      no sprouting after deep cavity preparation. There was no compensatory increase in
      CGRP- and SP-IR nerve fibers in the dental pulp after unilateral sympathectomy,
      although a significant increase in cells IR to CGRP and SP was found in the
      ipsilateral trigeminal ganglion. Unilateral sympathectomy induced a significant
      increase in immune cell density both in the inflamed and in the uninflamed dental
      pulp bilaterally. Our results demonstrate, for the first time, a trophic effect
      of the sympathetic nerves on immune cells in the dental pulp, indicating that an
      imbalance of sympathetic nerves may induce inflammation and pain in teeth.

PMID- 11312571
TI  - Group I metabotropic glutamate antagonist reduces acute neuronal degeneration and
      behavioral deficits after traumatic brain injury in rats.
AB  - Recent studies indicate that acute activation of Group I mGluRs following
      traumatic brain injury (TBI) contributes to the ensuing pathophysiology. The
      present study examined the effects of post-TBI administration of the selective
      mGluR1 antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) on acute
      neuronal degeneration in the hippocampus and long-term sensorimotor and
      learning/memory outcome. In Experiment 1, 26 rats received 0.4, 2.0, or 10.0 nmol
      AIDA or artificial CSF vehicle infusion into the hippocampus starting 5 min
      postinjury. At 24 h after TBI characteristic pyramidal cell degeneration was
      observed in Fluoro-Jade-stained coronal sections of the CA2/3 sectors of the
      dorsal hippocampus. The mean (+/-SEM) number of Fluoro-Jade-positive neurons in
      the 10 nmol AIDA group (184 +/- 32) was significantly less (P < 0.05) than the
      vehicle group (310 +/- 47). In Experiment 2, 20 rats were trained on sensorimotor
      and memory tasks prior to parasagittal fluid percussion TBI. Rats were
      administered 10 nmol AIDA or vehicle as in Experiment 1. Rats were assessed on
      beam walking and radial arm maze (RAM) performance weekly for 6 weeks after TBI.
      Acquisition of a Morris water maze (MWM) task was assessed on days 11-15 after
      TBI. The AIDA-treated group had significantly reduced deficits in beam walk, MWM,
      and RAM performance compared to the vehicle-treated group. These data indicate
      that injury-induced acute activation of mGluR1 receptors contributes to both the
      cellular pathology and the behavioral morbidity associated with TBI.

PMID- 11312572
TI  - Effects of nitric oxide on normal and ischemic cochlea of the guinea pig.
AB  - To determine whether nitric oxide (NO)/peroxynitrite plays any role in
      neurodestruction observed in ischemic cochlea of the guinea pig, the effects of
      NO donors like S-nitrosocysteine (S-NC) and nitroglycerin (NTG), peroxynitrite
      generators like 3-morpholinosydnonimine (SIN-1), peroxynitrite inhibitors like
      superoxide dismutase plus catalase (SOD/Cat), as well as NOS inhibitors like N(G)
      nitro-l-arginine methyl ether (L-NAME), were tested on normal and ischemic
      cochleae. Various concentrations of S-NC and SIN-1 were introduced into the
      perilymphatic space of normal guinea pig cochlea. Quantitative scanning electron
      microscopy of inner and outer hair cells was carried out 2 days later. To
      determine the level of NO in the cochlea after 20 to 120 min of ischemia,
      nitrites/nitrates in the perilymph were measured. The effects of NO on the
      ischemic cochlea were tested by infusion of SOD/Cat, L-NAME, S-NC, and NTG into
      the perilymphatic space just before decapitation. Introduction of fixative into
      the cochlea was delayed for 15 min to investigate the effects of the chemicals on
      nerve endings at the base of inner hair cells. The results showed that the level
      of nitrites/nitrates tended to decline with increasing time of ischemia. There
      was no significant hair cell loss in the cochleae treated with SIN-1 or S-NC. At
      15 min after ischemia, most of the nerve endings at the base of the inner hair
      cells were protected from damage when 1 mM S-NC or NTG was infused into the
      perilymph. Taken together, the results indicate that NO/peroxynitrite is unlikely
      to be involved in the neurodestruction in the ischemic cochlea. In fact,
      exogenous NO may have a neural protective effect.

PMID- 11312573
TI  - Chronically injured supraspinal neurons exhibit only modest axonal dieback in
      response to a cervical hemisection lesion.
AB  - This study examined the extent of axon retraction (dieback) exhibited by injured
      brain stem neurons in a chronic spinal cord injury (SCI) condition. Adult female
      rats subjected to a cervical (C3) hemisection lesion were sacrificed 1, 4, 8, or
      14 weeks after injury and the spinal cord from C1 to the lesion cavity was
      removed. One week prior to sacrifice, a microinjection of biotinylated dextran
      amine (BDA, 0.5 microliter) was made into the red nucleus, lateral vestibular
      nucleus, or medullary reticular formation of each animal. Horizontal cryostat
      sections were processed with avidin-HRP to detect supraspinal axons anterogradely
      labeled with BDA. Terminal end bulbs of axons were identified and their distance
      from the lesion site was measured by a computerized image analysis program. At
      all postinjury intervals, numerous rubrospinal, vestibulospinal, and
      reticulospinal tract axons were found immediately adjacent to the lesion site and
      over 60% of all terminals were within 500 micrometer at 1 and 4 weeks. The mean
      axonal distance of 450-500 micrometer from the lesion indicated that many injured
      axons had retracted farther than 500 micrometer from the lesion site; however,
      long-term maintenance of the mean axonal distance from the lesion at less than
      500 micrometer indicated the absence of progressive dieback after SCI. While some
      modest changes occur in specific supraspinal pathways following SCI, axonal
      retraction does not appear to be a contributing factor to the diminished
      regenerative effort by certain brain stem neurons that has been observed at long
      postinjury intervals.

PMID- 11312574
TI  - Primary structure of the Plasmodium vivax crk2 gene and interference of the yeast
      cell cycle upon its conditional expression.
AB  - The cdc2 gene product, a 34-kDa protein kinase, plays a universal role in the M
      phase of the eukaryotic cell cycle. To study the cell cycle regulation in
      malarial parasites, we have characterized a cdc2-related gene from the most
      widely distributed human malaria, Plasmodium vivax (Pvcrk2). The full-length
      Pvcrk2 revealed 90--99% homology with Crk2 proteins from other Plasmodium species
      and approximately 60% homology with p34(cdc2) proteins from higher eukaryotes. We
      used the temperature-sensitive Schizosaccharomyces pombe cdc2 mutant (cdc2
      33(ts)) for gene complementation studies. Expression of the full-length 33-kDa
      PvCrk2 protein, a truncated 27-kDa version, and two chimeric proteins in which we
      exchanged the N- and C-terminal regions of PvCrk2 with their S. pombe
      counterparts at the restrictive temperature in the mutant cdc2-33(ts) did not
      complement the cell cycle defect. However, conditional expression of the Pvcrk2
      genes or the chimera containing the C terminus from Spcdc2 in mutant cdc2-33(ts)
      cells produced cell-cycle-arrested phenotypes only in the induced state and at
      the permissive temperature. Our results thus provide the first compelling genetic
      evidence that the plasmodial Crk2 gene product(s) is capable of interfering with
      the well-conserved eukaryotic cell cycle machinery.

PMID- 11312575
TI  - Trypanosoma cruzi in the scent glands of Didelphis marsupialis: the kinetics of
      colonization.
AB  - This study examined the dynamics of colonization of Trypanosoma cruzi in the
      scent glands of the opossum Didelphis marsupialis following direct inoculation
      with 10(5) epimastigotes of isolate G-49 (an opossum-derived strain). One, three,
      and five days, 1 month, and 1 year after inoculation, scent glands were fixed for
      analysis using brightfield and electron microscopies. One day after inoculation
      the parasites, mainly as epimastigotes, were randomly distributed into the lumen.
      From the third day on, the parasites still in the form of epimastigotes tended to
      concentrate closer to the epithelium. The flagellates reached the definitive
      distribution pattern on the fifth day, when they formed huge clusters deep into
      the foveae. In samples collected 1 month and 1 year after inoculation, the ratio
      of epimastigotes:trypomastigotes was 1:1, with epimastigotes predominating near
      the epithelium and trypomastigotes far from it. Our observations suggest that T.
      cruzi grows continuously in the scent glands and does not depend on adhesion to
      promote metacyclogenesis. Metacyclogenesis far from the epithelium seems to be an
      important selective advantage to both host and parasite, since it assures the
      elimination of the infective forms of the parasite when the host expels the
      glands' contents, which occurs in frightening situations or at times of stress.
      The morphological characteristics of infected and noninfected scent glands using
      transmission and scanning electron microscopies were also described.

PMID- 11312576
TI  - Application of flow cytometry and microscopical methods to characterize the
      effect of herbal drugs on Leishmania Spp.
AB  - The World Health Organization has identified leishmania sis as a major public
      health problem, particularly in Africa, Asia, and Latin America. About 1.5 to 2
      million people are affected annually by this parasitic infection. As there is no
      vaccine, there is still a strong need for sufficient drugs. In a preliminary
      screening, extracts of 50 different plants were evaluated for their possible
      leishmanicidal activity against the promastigote form of Leishmania mexicana
      amazonensis. Eighteen extracts showed at least 50% inhibition at 100 microg/ml.
      The ethanolic extract from Yucca filamentosa L. showed the strongest
      leishmanicidal activity (100% inhibition at 5 microg/ml). The bioactivity-guided
      fractionation of this extract led to the isolation of three main components
      (Yuccasaponins MC 1--3). In further experiments, the effect of Yuccasaponin MC 3
      on the promastigote form of L. mexicana amazonensis was quantified and
      characterized using flow cytometry and specific fluorescent dyes [propidium
      iodide, Syto 9, and DiBAC(4)(3)]. The data revealed that the membrane of the
      promastigote is attacked. The effect of Yuccasaponin MC 3 on intracellular forms
      (amastigote) was also characterized; green fluorescent protein-transfected
      Leishmania major were used. By this method, an inhibition of intracellular growth
      of L. major was demonstrated. This paper shows that, together, flow cytometry and
      microscopy are quick, sensitive, and easily reproducible methods to describe the
      effects of drugs on parasites.

PMID- 11312577
TI  - Fasciola: kinetics and quality of humoral responses to fatty acid binding protein
      and cathepsin l following delivery as DNA vaccines in mice.
AB  - The humoral response to DNA vaccination of mice with two important Fasciola
      antigens has been investigated. Both F. gigantica fatty acid binding protein
      (FABP) and F. hepatica cathepsin L5 (FhCatL5) were shown to be expressed in COS 7
      cells and induced a humoral response when delivered as secretory constructs in
      mice. FABP induced an IgGl dominant response, with significant IgE, IgG2a, and
      IgG2b responses also present, indicating a mixed Th1/Th2 response. The total Ig
      response peaked at 1:24,500 and antibody titers were sustained for at least 32
      weeks. In contrast, the delivery of FABP as a nonsecreted construct did not
      result in the induction of a measurable humoral response. FhCatL5 was delivered
      as a secretory construct, with secretion mediated by the native F. hepatica
      signal sequence, which was shown to operate in COS 7 cells. The humoral response
      peaked at 1:2000 at week 8 and was sustained for at least 20 weeks. Antibody
      isotype analysis demonstrated a Th2-like response, which was qualitatively
      different from that obtained for FABP with an IgE dominant response, and lower
      titers to IgG1 and IgG3. The results demonstrate that Fasciola antigens can be
      delivered as DNA vaccines, but that the quality of the response varies between
      antigens and is influenced by the method of vaccine delivery.

PMID- 11312578
TI  - Adaptation of Leishmania cells to in vitro culture results in a more efficient
      reduction and transport of biopterin.
AB  - Leishmania major and Leishmania donovani cells freshly isolated from infected
      animals divided slowly as axenic promastigotes but the addition of biopterin in
      the culture medium greatly enhanced their growth. However, when cells were
      subjected to serial passages and adapted to culture, this growth-promoting effect
      of biopterin was no longer observed. Genetic analysis of these culture-adapted
      Leishmania cells demonstrated that the genes coding for the pterin reductase PTR1
      or for the biopterin transporter BT1 were over-expressed. This suggests that
      Leishmania cells adapted to culture were more efficient in utilizing biopterin,
      an essential growth factor in Leishmania.

PMID- 11312579
TI  - Purification of N-acetyl-beta-D-hexosaminidase from Trichomonas vaginalis.

PMID- 11312580
TI  - Trypanosoma cruzi: mucin pseudogenes organized in a tandem array.

PMID- 11312581
TI  - Paleoenvironmental reconstruction of middle Miocene paleosols bearing
      Kenyapithecus and Victoriapithecus, Nyakach Formation, southwestern Kenya.
AB  - Paleosols in the middle Miocene (15 Ma) Nyakach Formation at Kaimogool, near
      Sondu, southwestern Kenya have yielded specimens of the early cercopithecoid
      Victoriapithecus macinnesi and the early kenyapithecine Kenyapithecus africanus,
      and can be used as evidence for the environmental mosaic occupied by these
      primates. Five distinct types of paleosols (pedotypes) are recognized in the
      Nyakach Formation section at Kaimogool South. The most common paleosols are
      reddish brown, silty calcareous profiles with blocky structure and large root
      traces (Ratong pedotype) which are interpreted as soils of well-drained, dry
      bushland or thicket (nyika). Weakly developed paleosols associated with
      paleochannels (Dhero pedotype) represent wooded grassland early in the ecological
      succession from streamside flooding. One of these paleosols has yielded a fossil
      flora of grasses and small-leaved dicots like those of modern semi-arid wooded
      grassland. Crumb structured, calcareous paleosols with iron-manganese nodules
      (Yom pedotype) are interpreted to represent seasonally waterlogged, wooded
      grassland (dambo or vlei). Thick, red clayey, calcareous paleosols with blocky
      ped structure and large root traces (Tut pedotype) are interpreted as soils of
      well-drained dry woodland. Other blocky-structured, gray to brown calcareous
      paleosols with iron-manganese nodules (Chido pedotype) are interpreted as soils
      of seasonally waterlogged, riparian dry woodland. Fossil soils, plants and
      gastropods are evidence of an unusually dry (300-500 mm mean annual
      precipitation) habitat for apes, consisting of a vegetational mosaic dominated by
      dry woodland, bushland and thickets with few areas of seasonally waterlogged
      grassland. Fossils of V. macinnesi are rare from Nyakach, but were found in
      paleosols representative of bushland and thicket habitats (Ratong). Fossils of
      the ape K. africanus were found within paleosols indicative of dry woodland
      (Tut). Other paleosol types representative of seasonally dry dambo grassland
      (Yom), colonizing grassland (Dhero) or riparian woodland (Chido) are also
      represented, but have not yet produced primate fossils.

PMID- 11312582
TI  - Woodworking activities by early humans: a plant residue analysis on Acheulian
      stone tools from Peninj (Tanzania).
AB  - The emergence of the Acheulian stone tool industry, between 1.7 and 1.5 m.y.a.,
      constitutes one of the earliest evidences of complex behavior in the process of
      human evolution. The major technological breakthrough with the Acheulian industry
      was the beginning of the manufacture of bifacially shaped heavy-duty tools.
      Handaxes made with a predetermined form and a high degree of symmetry are the
      main characteristic of the Acheulian tradition. The tools are shaped through a
      long knapping sequence with a remarkable increase in the technical skills of the
      makers, compared with the older Oldowan tradition, implying a high degree of
      planning and foresight. Until recently, the function of these early bifacial
      tools remained unknown. A large number of these artefacts were found at Peninj in
      Tanzania, and phytolith analyses on handaxes have yielded for the first time
      unambiguous evidence of their function as woodworking tools.

PMID- 11312583
TI  - Morphometric variation in the hominoid orbital aperture: a case study with
      implications for the use of variable characters in Miocene catarrhine
      systematics.
AB  - Variable characters are ubiquitous in hominoid systematics and present a number
      of unique problems for phylogenetic analyses that include extinct taxa. As yet,
      however, few studies have quantified ranges of variation in complex morphometric
      characters within extant taxa and then used those data to assess the consistency
      with which discrete character states can be applied to poorly represented fossil
      species. In this study, ranges of intrageneric morphometric variation in the
      shape of the hominoid orbital aperture are estimated using exact randomization of
      average pairwise taxonomic distances (ATDs) derived from size-adjusted centroid,
      height-width, and elliptic Fourier (EF) variables. Using both centroid and height
      width variables, 19 of the 21 possible ATDs between individuals representing
      seven extinct catarrhine taxa (Aegyptopithecus, Afropithecus, Ankarapithecus,
      Ouranopithecus, Paranthropus, Sivapithecus and Turkanapithecus) can be observed
      within a single extant hominoid subspecies, although generally with low
      probabilities. A resampling study is employed as a means for gauging the effect
      that this intrataxonomic variation may have on the consistency with which
      discrete orbital shape character states can be delimited given the small sample
      sizes available for most Miocene catarrhine taxa preserving this feature (i.e.,
      n=1). For each type of morphometric variable, 100 cluster (UPGMA) analyses of
      pairwise ATDs are performed in which a single individual is randomly selected
      from each hominoid genus and analyzed alongside known extinct taxa; consensus
      trees are computed in order to obtain the frequencies with which different shape
      clusters appeared in each of the three analyses. The two major clusters appearing
      most frequently in all three consensus trees are found in only 57% (centroid
      variables), 49% (height-width variables), and 36% (EF variables) of these trees.
      If ranges of variation within represented extinct taxa could also be estimated,
      these frequencies would certainly be far lower. Hominoids clearly exhibit
      considerable intrageneric, intraspecific, and even intrasubspecific variation in
      orbit shape, and substantial morphometric overlap exists between taxa;
      consequently, discrete character states delimiting these patterns of continuous
      variation are likely to be highly unreliable in phylogenetic analyses of living
      and extinct species, particularly as the number of terminal taxa increases.
      Morphological phylogenetic studies of extant catarrhines that assess the effect
      of different methods (e.g., use of objective a priori weighting or frequency
      coding of variable characters, inclusion vs. exclusion of variable characters,
      use of specific vs. supraspecific terminal taxa) on phylogenetic accuracy may
      help to improve the techniques that systematists employ to make phylogenetic
      inferences about extinct taxa.

PMID- 11312584
TI  - Enamel hypoplasia in the deciduous teeth of early Miocene catarrhines: evidence
      of perinatal physiological stress.
AB  - Enamel hypoplasia (EH) is a deficiency in enamel thickness due to physiological
      insults that compromise ameloblast function during the secretory phase of
      amelogenesis. The prevalence of EH in the deciduous teeth of nonhuman primates is
      largely unknown. One exception is the recent discovery of EH in the deciduous
      teeth of extant great apes which exhibit significant differences in prevalence
      between genera (Lukacs, 1999 a, 2000 a, Am. J. phys. Anthrop.110, 351-363). EH in
      deciduous teeth of other primates, living and fossil, remain undocumented. This
      communication describes a "plane form" type of EH known as localized hypoplasia
      of primary canines (LHPC) (Skinner, 1986 a, Am. J. phys. Anthrop.69, 59-69) in
      early Miocene catarrhines from Kenya. Specimens were examined macroscopically,
      with a 10x hand lens and with a variable power (10-30x) binocular microscope.
      Federation Dentaire International (FDI)/Defects of Dental Enamel (DDE) standards
      were employed in recognition and recording of enamel defects (Federation Dentaire
      International, 1982, Int. Dent. J.32, 159-167; Clarkson, 1989, Adv. Dental Res.3,
      104-109). Size, shape and location of defects were measured and recorded on an
      outline drawing of the tooth crown. The Kenya National Museum study sample
      includes six genera of early Miocene catarrhines (n=66 specimens, with n=80
      teeth). Seven deciduous teeth were afflicted with EH, yielding an overall
      prevalence of 8.75%. Two taxa, Kalepithecus (n=1 deciduous canine) and Proconsul
      (n=3 deciduous canines), were affected with LHPC. Expression of LHPC in fossil
      catarrhines is consistent with the expression of EH observed in skeletal samples
      of extant great apes. This report establishes an approximately 17-23 Ma antiquity
      for EH among early catarrhines and suggests that the neonatal stage of
      ontogenetic development was sufficiently stressful physiologically to produce
      disruption in amelogenesis. These physiological stresses impacted neonates of
      fossil taxa with a wide range of adult body sizes, from large-bodied Proconsul
      major ( approximately 75 kg) to one of the smaller-bodied catarrhines,
      Kalepithecus ( approximately 5 kg).

PMID- 11312585
TI  - Histomorphometric age assessment of the Boxgrove 1 tibial diaphysis.
AB  - Histomorphometric analysis of a medial midshaft chip from the Middle Pleistocene
      (ca. 500 ka BP) hominid tibia from Boxgrove, U.K. provides a modal age-at-death
      estimate at the end of the fourth decade of life. This makes Boxgrove 1 one of
      the older known and systematically aged Middle Pleistocene hominid specimens, and
      it reinforces the pattern of an underrepresentation of older adults observed in
      Middle and Late Pleistocene archaic Homo samples.

PMID- 11312586
TI  - Primate origins: evolutionary change in digital ray patterning and segmentation.
AB  - This study presents evidence that the first primates share with extant lemurs,
      tarsiers, and anthropoids hand proportions unlike those of their close relatives,
      the tree shrews (Scandentia), colugos (Dermoptera), and plesiadapiforms.
      Specifically, early primates as well as modern strepsirhines and haplorhines have
      relatively short metacarpals and long proximal phalanges giving them a grasping,
      prehensile hand. Limb development was studied in the primate Microcebus murinus
      and a comparative sample of rodents, artiodactyls, and marsupials to investigate
      the role of embryonic patterning in the morphogenesis and evolution of primate
      hand proportions. Comparative analysis shows that the derived finger proportions
      of primates are generated during the early phases of digital ray patterning and
      segmentation, when the interzone cells marking the presumptive metacarpo- and
      interphalangeal joints first appear. Interspecific variation in relative digit
      and metapodial proportions therefore has high developmental penetrance; that is,
      adult differences are observed at early ontogenetic stages. The paleontological,
      comparative, and developmental data are therefore consistent with the hypothesis
      that the early Cenozoic origin of primates involved an evolutionary change in
      digital ray pattern formation ultimately yielding a grasping, prehensile hand.

PMID- 11312587
TI  - Geologic context and age of the Perning/Mojokerto Homo erectus, East Java.

PMID- 11312588
TI  - Morphological models of radiate accretive growth and the influence of
      hydrodynamics.
AB  - In many marine sessile organisms (for example sponges and stony corals) the
      skeleton is formed by an accretive growth process, where layers of material are
      secreted on top of each other in a surface normal deposition process. In many of
      these organisms the growth process exhibits a strong morphological plasticity due
      to differences in exposure to water movement. In general, many of these organisms
      tend to form thin-branching growth forms under sheltered conditions, while the
      growth form gradually transforms into a more compact shape when the exposure of
      water movement increases. In this paper, we investigate this phenomenon by
      combining a three-dimensional simulation model of radiate accretive growth driven
      by the local availability of simulated food particles and a model, based on the
      lattice Boltzmann method, for simulating food particle distributions caused by a
      combination of flow and diffusion. In the simulations two different models of a
      suspension feeder with accretive growth were compared. In the first model, the
      deposition process is exclusively driven by the local availability of food
      particles, in the second model the deposition process was determined by the
      combination of local amount of contact to the environment and availability of
      food particles. In the simulations it was found that hydrodynamics has a strong
      impact on the overall morphologies which develop in the accretive growth process.
      In the model exclusively driven by the local availability of food particles,
      column-shaped objects emerged under diffusion conditions, while more spherical
      and lobed object were found for the flow-dominated case. In the simulations, the
      Peclet number was varied independently from the Reynolds number, which was kept
      at a relatively low constant value. In a range of increasing Peclet numbers,
      indicating an increasing influence of hydrodynamics, the simulated morphologies
      gradually transformed from thin-branching ones into more spherical and compact
      morphologies in the model where deposition was controlled by the local
      availability of food particles and the local amount of contact with the
      environment.

PMID- 11312589
TI  - Cybernetic formulation of the definition of life.
AB  - A definition of life (a living individual) in cybernetic terms is proposed. In
      this formulation, life (a living individual) is defined as a network of inferior
      negative feedbacks (regulatory mechanisms) subordinated to (being at service of)
      a superior positive feedback (potential of expansion). It is suggested that this
      definition is the minimal definition, necessary and sufficient, for life to be
      distinguished from inanimate phenomena and, as such, it describes the essence of
      life. Subsequently, a quantitative expression for the amount of the biologically
      relevant ("purposeful") information (as opposed to the amount of information in
      the thermodynamic sense) is proposed. This is followed by the application of the
      formulated approach to different phenomena of a dubious status existing presently
      on the Earth as well as to the process of origination of life on our planet.

PMID- 11312590
TI  - The effect of evolution on host-parasitoid systems.
AB  - It is well known that a simple first-order difference equation can exhibit
      complex population dynamics, such as sustained oscillations and chaos. An
      interesting problem is whether such oscillatory dynamics are expected to occur in
      real populations. This paper assumes that the resident system is composed of 1
      host and 1-parasitoid and that only the host is allowed to evolve, but not the
      parasitoid. Based on the invasibility of a host to host-parasitoid systems, we
      investigate the dynamics of the host-parasitoid system favored by natural
      selection. We consider two cases. In the first case, the host's evolution
      involving both the intrinsic growth rate and the sensitivity to density is
      considered. In the second case, the host's evolution involving both the intrinsic
      growth rate and the vulnerability to the parasitoid is considered. In both cases,
      we see that the dynamics with a stable equilibrium will not be favored by natural
      selection without the trade-off between the host's traits which are allowed to
      evolve. The host-parasitoid system with a stable equilibrium will be eventually
      invaded by a host type that develops an unstable equilibrium with the parasitoid.
      If there is a trade-off between the host's traits which are allowed to evolve, a
      host-parasitoid system with a stable equilibrium can be favored by natural
      selection.

PMID- 11312591
TI  - Topological nature of the genetic code.
AB  - A model for topological coding of proteins is proposed. The model is based on the
      capacity of hydrogen bonds (property of connectivity) to fix conformations of
      protein molecules. The protein chain is modeled by an n -arc graph with the
      following elements: vertices (alpha -carbon atoms), structural edges (peptide
      bonds) and connectivity edges (virtual edges connecting non-adjacent atoms). It
      was shown that 64 conformations of the 4-arc graph can be described in the binary
      system by matrices of six variables which form a supermatrix containing four
      blocks. On the basis of correspondences between the pairs of variables in
      matrices and four letters of the genetic code matrices and supermatrix are
      converted, respectively, into the triplets and the table of the genetic code. An
      algorithm admitting computer programming is proposed for coding the n -arc graph
      and protein chain. Connectivity operators (polar amino acids) are assigned to
      blocks of triplets coding for cyclic conformations (G, A-in the second position),
      while anti-connectivity operators (non-polar amino acids) correspond to blocks of
      triplets coding for open conformations (C, U-in the second position). Amino acids
      coded by triplets differing by the first base have different structures. The
      third base for C, U and G, A is degenerated. Properties of the real genetic code
      are in full agreement with the model. The model provides an insight into the
      topological nature of the genetic code and can be used for development of
      algorithms for the prediction of the protein structure.

PMID- 11312592
TI  - Detours in bird migration.
AB  - Bird migration routes often follow detours where passages across ecological
      barriers are reduced in extent. This occurs in spite of the fact that long
      barrier crossings are within the birds' potential flight range capacity. Long
      distance flights are associated with extra energy costs for transport of the
      heavy fuel loads required. This paper explores how important the fuel transport
      costs, estimated on the basis of flight mechanics, may be to explain detours for
      birds migrating by flapping flight. Maximum detours in relation to expanse of the
      barrier are predicted for cases where birds travel along the detour by numerous
      short flights and small fuel reserves, divide the detour into a limited number of
      flight steps, and where a reduced barrier passage is included in the detour. The
      principles for determining the optimum route, often involving a shortcut across
      part of the barrier, are derived. Furthermore, the effects of differences in fuel
      deposition rates and in transport costs for the profitability of detours are
      briefly considered. An evaluation of a number of observed and potential detours
      in relation to the general predictions of maximum detours, indicates that
      reduction of fuel transport costs may well be a factor of widespread importance
      for the evolution of detours in bird migration at wide ecological barriers.

PMID- 11312593
TI  - Patch dynamics and metapopulation theory: the case of successional species.
AB  - We present a mathematical framework that combines extinction-colonization
      dynamics with the dynamics of patch succession. We draw an analogy between the
      epidemiological categorization of individuals (infected, susceptible, latent and
      resistant) and the patch structure of a spatially heterogeneous landscape
      (occupied-suitable, empty-suitable, occupied-unsuitable and empty-unsuitable).
      This approach allows one to consider life-history attributes that influence
      persistence in patchy environments (e.g., longevity, colonization ability) in
      concert with extrinsic processes (e.g., disturbances, succession) that lead to
      spatial heterogeneity in patch suitability. It also allows the incorporation of
      seed banks and other dormant life forms, thus broadening patch occupancy dynamics
      to include sink habitats. We use the model to investigate how equilibrium patch
      occupancy is influenced by four critical parameters: colonization rate,
      extinction rate, disturbance frequency and the rate of habitat succession. This
      analysis leads to general predictions about how the temporal scaling of patch
      succession and extinction-colonization dynamics influences long-term persistence.
      We apply the model to herbaceous, early-successional species that inhabit open
      patches created by periodic disturbances. We predict the minimum disturbance
      frequency required for viable management of such species in the Florida scrub
      ecosystem.

PMID- 11312594
TI  - The non-universality of the genetic code: the universal ancestor was a progenote.
AB  - The coevolution theory of genetic code origin (Wong, J.T. 1975, Proc. Natl Acad.
      Sci. U.S.A.72, 1909-1912) is assumed here to be substantially correct. This
      theory is based on the strict parallelism of the biosynthetic relationships
      between amino acids and the organization of the genetic code and postulates that
      these relationships were mediated by tRNA-like molecules on which the
      biosynthetic transformations between precursor and product amino acids took
      place. These transformations underlay the mechanism that gave rise to genetic
      code organization. One of the pathways which represents these transformations
      found in current organisms, and which are thus probably molecular fossils, is the
      Met-tRNA(fMet)-->fMet-tRNA(fMet)pathway. This pathway is present only in the
      Bacteria domain. This along with other observations and arguments leads us to
      believe that this pathway is a clear violation of the universality of the genetic
      code. Furthermore, the presence of this pathway only in the Bacteria domain seems
      to imply that the translation apparatus was still rapidly evolving when this
      pathway was fixed. This, in turn, appears to imply that the last universal common
      ancestor was a progenote. Finally, the implications that the finding of this
      pathway has for the stereochemical theory of genetic code origin are discussed.

PMID- 11312595
TI  - Turbulent transport of suspended particles and dispersing benthic organisms: the
      hitting-distance problem for the local exchange model.
AB  - The local exchange model developed by McNair et al. (1997) provides a stochastic
      diffusion approximation to the random-like motion of fine particles suspended in
      turbulent water. Based on this model, McNair (2000) derived equations governing
      the probability distribution and moments of the hitting time, which is the time
      until a particle hits the bottom for the first time from a given initial
      elevation. In the present paper, we derive the corresponding equations for the
      probability distribution and moments of the hitting distance, which is the
      longitudinal distance a particle has traveled when it hits the bottom for the
      first time. We study the dependence of the distribution and moments on a
      particle's initial elevation and on two dimensionless parameters: an inverse
      Reynolds number M (a measure of the importance of viscous mixing compared to
      turbulent mixing of water) and the Rouse number s(a measure of the importance of
      deterministic gravitational sinking compared to stochastic turbulent mixing in
      governing the vertical motion of a particle). We also compute predicted hitting
      distance distributions for two published data sets. The results show that for
      fine particles suspended in moderately to highly turbulent water, the hitting
      distance distribution is strongly skewed to the right, with mode<median<mean.
      Because of the distribution's thick upper tail, there is a significant
      probability that a particle's hitting distance will greatly exceed the mean. The
      results also show that the position of the mode depends strongly on a particle's
      initial elevation but, compared to the median or mean, is relatively insensitive
      to s. These results are broadly similar to those obtained by McNair (2000) for
      the hitting-time distribution, but the distribution and moments of the hitting
      distance are noticeably more sensitive to M than are the corresponding properties
      of the hitting time. Comparison of predicted hitting-distance distributions with
      data of Cushing et al. (1993) on settling distances of fine particulate organic
      matter in natural streams supports the view that such particles commonly fail to
      settle the first time they hit the stream bed.

PMID- 11312596
TI  - A comment on two models of the remigration interval in marine turtles.

PMID- 11312597
TI  - Aggregate statistical measures and metapopulation dynamics.
AB  - There are two main types of metapopulation models. Spatially implicit models are
      analytically tractable but neglect spatial heterogeneities. Spatially explicit
      models are more realistic but too complex. In this paper, I build a bridge
      between both approximations. I derive a new metapopulation model using a well
      known technique in population genetics. Spatial heterogeneities are captured by
      an aggregate statistical measure of spatial correlation. When this correlation is
      zero, i.e., space is homogeneous, the model becomes the well-known Levins' model.
      As spatial correlation increases, equilibrium patch occupancy decreases from what
      would be expected under the spatially homogeneous assumption. I proceed by
      testing how well spatial complexities from a spatially explicit simulation can be
      encapsulated by such an aggregate statistical measure.

PMID- 11312598
TI  - Juxtaposition of CNR protocadherins and reelin expression in the developing
      spinal cord.
AB  - The CNR (cadherin-related neuronal receptors) family of protocadherins is of
      great interest because of their potential roles as molecular tags in the
      formation of specific synaptic connections, and as receptors for reelin, during
      neuronal migration, and cell body positioning. In order to know more about
      potential functions of CNRs we have mapped their expression during mouse nervous
      system development and compared their expression with that of reelin and its
      intracellular effector Dab1 in several tissues. In spinal cord, CNRs and Dab1 are
      expressed in motoneurons, while reelin is located in adjacent cells. In the
      hindbrain, there is a differential expression of CNRs and Dab1 in various motor
      nuclei. In the retina and olfactory system, we observe CNR and reelin expression
      but not that of Dab1. These results provide new insights into the potential
      functions of CNRs and their possible integration in the reelin pathway during
      development.

PMID- 11312599
TI  - Cytoskeletal reorganization during the formation of oligodendrocyte processes and
      branches.
AB  - During oligodendrocyte development, signals relevant to process formation must be
      transduced into appropriate changes in cytoskeletal organization. We have
      explored how microtubules and microfilaments interact during the outgrowth and
      branching of oligodendrocyte processes in culture. We observed that
      microfilaments are enriched in the peripheral region beneath the plasma membrane
      and constitute the major cytoskeletal element at the leading edge of the process,
      which is also enriched in the B-isoform of the non-muscle myosin II heavy chain.
      Microtubules form a dense bundle within the process and splay before extending
      into the leading edge and branches, following tracks laid by microfilaments.
      Pharmacologic disruption of microfilaments and microtubules compromised normal
      process outgrowth and branching. However, microtubules rapidly reinvaded most
      processes after removal of both antimicrotubule and antimicrofilament drugs, but
      the reinvasion was severely compromised if the antimicrofilament drug was
      retained. These results are consistent with the hypothesis that microfilaments
      guide the local reorganization of microtubules for the elongation of
      oligodendrocyte processes and the formation of new branches.

PMID- 11312600
TI  - GABA(B) receptors couple directly to the transcription factor ATF4.
AB  - The inhibitory neurotransmitter gamma-aminobutyric acid (GABA), acts at
      ionotropic (GABA(A) and GABA(C)) and metabotropic (GABA(B)) receptors. Functional
      GABA(B) receptors are heterodimers of GABA(B(1)) and GABA(B(2)) subunits. Here we
      show a robust, direct, and specific interaction between the coiled-coil domain
      present in the C-terminus of the GABA(B(1)) subunit and the transcription factor
      ATF4 (also known as CREB2). ATF4 and GABA(B(2)) binding to the GABA(B(1)) subunit
      were mutually exclusive. In rat hippocampal neurons native GABA(B(1)) showed
      surprisingly little similarity to GABA(B(2)) in its subcellular distribution.
      GABA(B(1)) and ATF4, however, were highly colocalized throughout the cell and
      displayed a punctate distribution within the dendrites. Activation of GABA(B)
      receptors in hippocampal neurons caused a dramatic translocation of ATF4 out of
      the nucleus into the cytoplasm. These data suggest a novel neuronal signaling
      pathway that could regulate the functional expression of GABA(B) receptors and/or
      modulate gene transcription.

PMID- 11312601
TI  - In vivo internalization of the somatostatin sst2A receptor in rat brain: evidence
      for translocation of cell-surface receptors into the endosomal recycling pathway.
AB  - To determine whether cellular compartmentalization of somatostatin receptors can
      be regulated in vivo, we examined the immunocytochemical distribution of the
      sst2A receptor (sst2AR) after stereotaxical injections of somatostatin analogs
      into the rat parietal cortex. Whereas CH-275, a sst1R agonist, failed to induce
      changes in the diffuse sst2AR immunostaining pattern characteristic of control
      animals, somatodendritic profiles displaying intracytoplasmic immunoreactive
      granules became apparent short-term after injection of either somatostatin or the
      sst2R agonist octreotide. Confocal microscopy revealed that 90% of sst2AR
      immunoreactive endosome-like organelles displayed transferrin receptor
      immunoreactivity. At the electron microscopic level, the percentage of sst2AR
      immunoparticles dramatically decreased at the plasmalemma of perikarya and
      dendrites after octreotide injection. Conversely, it significantly increased in
      endosomes-like organelles. These results demonstrate that sst2ARs undergo, in
      vivo, rapid and massive internalization into the endocytic recycling compartment
      in response to acute agonist stimulation and provide important clues toward
      elucidating somatostatin receptor signaling in the mammalian brain.

PMID- 11312602
TI  - Disruption of the GluR2-NSF interaction protects primary hippocampal neurons from
      ischemic stress.
AB  - A specific interaction between the AMPA receptor subunits GluR2 and GluR3 and the
      fusion protein NSF has recently been identified. Disruption of this interaction
      by adenoviral-mediated expression of a peptide (pep2m) corresponding to the NSF
      binding region of GluR2 results in a dramatic reduction in surface expression of
      AMPA receptors in primary hippocampal neurons. Here we report that expression of
      pep2m from a recently developed neuronal-specific adenoviral system gave
      significant neuroprotection to primary CA1-CA3 hippocampal neurons following
      stimulation with kainate (KA) and this was accompanied by a reduction in Ca(2+)
      influx. Protection was also observed following glucose deprivation and exposure
      to ischemic buffer in the absence of any NMDA receptor antagonists. These results
      provide strong evidence that AMPA receptors play a direct role in mediating
      postischemic neurotoxicity.

PMID- 11312603
TI  - Overexpression of MATH1 disrupts the coordination of neural differentiation in
      cerebellum development.
AB  - An essential role for the bHLH transcription factor MATH1 in the formation of
      cerebellar granule cells was previously demonstrated in a Math1 null mouse. The
      function of regulated levels of MATH1 in granule cell development is investigated
      here using a gain-of-function paradigm. Overexpression of Math1 in its normal
      domain in transgenic mice leads to early postnatal lethality and perturbs
      cerebellar development. The cerebellum of the (B)MATH1 transgenic neonate is
      smaller with less foliation, particularly in the central vermal regions, when
      compared to wild-type cerebella. A detailed analysis of multiple molecular
      markers in brains overexpressing Math1 has revealed defects in the
      differentiation of cerebellar granule cells. NeuroD and doublecortin, markers
      normally distinguishing the discrete layered organization of granule cell
      maturation in the inner EGL, are aberrantly expressed in the outer EGL where
      MATH1-positive, proliferating cells reside. In contrast, TAG-1, a later marker of
      developing granule cells that labels parallel fibers, is severely diminished. The
      elevated MATH1 levels appear to drive expression of a subset of early
      differentiation markers but are insufficient for development of a mature TAG-1
      expressing granule cell. Thus, balanced levels of MATH1 are essential for the
      correct coordination of differentiation events in granule cell development.

PMID- 11312604
TI  - The POU gene Brn-5 is induced by neuregulin and is restricted to myelinating
      Schwann cells.
AB  - The POU family of transcription factors plays a vital role in controlling cell
      fate determination and the timing of cellular events in a number of tissues,
      including the nervous system. One such POU protein, SCIP, is expressed by Schwann
      cells in a tightly delimited developmental window termed promyelination. In the
      PNS, promyelination is functionally defined as the period following Schwann cell
      exit from the cell-cycle, but prior to the onset of myelination. Previous
      transgenic and gene ablation studies have shown that SCIP is a myelin-competence
      factor in the Schwann cell, where it is required for entry into, and the
      subsequent maintenance of promyelination. To further understand the molecular
      biology of the promyelination-to-myelination transition in the Schwann cell, we
      have undertaken a series of DDRTPCR studies to identify genes that are expressed
      during this phenotypic flux. Through these studies we have identified another POU
      gene, Brn-5, the expression of which has not previously been appreciated in the
      Schwann cell. Here we show that the developmental expression patterns of Brn-5
      and SCIP are inverse, with Brn-5 stably expressed in the adult myelinating
      Schwann cell, but virtually absent during promyelination. Further, we show that
      the induction of the two genes is independent, with SCIP induction requiring
      activation of adenyl cyclase, whereas Brn-5 induction requires only GGF2. In
      addition, the induction of Brn-5 is exquisitely sensitive to neuregulin
      concentration, with higher levels inhibiting its expression. Following nerve
      injury, when GGF2 levels are elevated in the distal nerve, Brn-5 expression
      disappears, and SCIP is reexpressed.

PMID- 11312605
TI  - Apoptosis and ROS detoxification enzymes correlate with cytochrome c oxidase
      deficiency in mitochondrial encephalomyopathies.
AB  - The aim of this work was to investigate in muscle the role of apoptosis and of
      oxidative stress in mitochondrial disorders with dysfunction of respiratory
      chain. In patients with cytochrome c oxidase deficiency (COX) we found a variable
      number of myofibers with apoptotic nuclei that matched with the level of
      enzymatic reduction and roughly correlated with muscle weakness. In parallel, a
      positive immunostaining for apoptosis-related proteins and Mn and Cu/Zn
      superoxide dismutase (SOD) were mostly localized in COX-negative fibers.
      Moreover, glutathione peroxidase activity was increased in muscles with high
      number of SOD-positive myofibers and prominent apoptotic features. No signs of
      apoptosis were observed in patients with deficiencies of complexes I and II and
      without muscle weakness. These data suggest that apoptosis along with increased
      ROS production, revealed by anti-oxidant enzymes overexpression, may play an
      important role in the pathophysiology of mitochondrial diseases associated with
      COX deficiency.

PMID- 11312606
TI  - Sustained effects of gene-activated matrices after CNS injury.
AB  - We show that when gene-activated matrices (GAM) are placed between the proximal
      and distal stumps of severed rat optic nerves, DNA is retained within the GAM,
      promoting sustained transgene expression in the optic nerve, in the GAM itself,
      and, more importantly, in axotomized retinal ganglion cells (RGC). Plasmids that
      encode basic fibroblast growth factor (FGF2), brain-derived neurotrophic factor
      (BDNF), and neurotrophin-3 (NT3) promote sustained survival of RGC for over 3
      months after the initial injury. These findings suggest that immobilized DNA
      implanted into a CNS lesion will be delivered by axon terminal uptake and
      retrograde transport to axotomized neurons. GAM may therefore be a useful agent
      for promoting sustained neuron survival and axon regeneration. Whether further
      optimization of the matrices, plasmids, promoters, and genes present in the GAM
      will promote even more survival or, alternatively, axon regeneration remains to
      be determined.

PMID- 11312607
TI  - Cascade of caspase activation in potassium-deprived cerebellar granule neurons:
      targets for treatment with peptide and protein inhibitors of apoptosis.
AB  - Cerebellar granule neurons (CGN) cultured in the presence of serum and
      depolarizing potassium concentrations undergo apoptosis when switched to serum
      free medium containing physiological potassium concentrations. Here we show that
      processing of the key protease, caspase-3, depends on the activation of caspase
      9, but not of caspase-8. Selective peptide inhibitors of caspase-9 block
      processing of caspase-3 and caspase-8 and inhibit apoptosis, whereas a selective
      inhibitor of caspase-8 blocks neither processing of caspase-3 nor cell death. The
      data obtained with peptide inhibitors were confirmed by adenovirally mediated
      ectopic expression of the cytokine response modifier A (crmA), the baculovirus
      protein p35, and the X chromosome-linked inhibitor of apoptosis (XIAP). Further,
      caspase-8-activating death receptors do not mediate apoptosis in CGN and
      potassium withdrawal-induced apoptosis evolves unaltered in gld or lpr mice,
      which harbor mutations in the CD95/CD95 ligand system. Thus, neuronal apoptosis
      triggered by potassium deprivation is death receptor-independent but involves the
      mitochondrial pathway of caspase activation.

PMID- 11312608
TI  - The cyclic AMP-mediated expression of acetylcholinesterase in myotubes shows
      contrasting activation and repression between avian and mammalian enzymes.
AB  - Cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signalling pathway has been
      proposed to regulate acetylcholinesterase (AChE) expression in chick muscle;
      however, its role in mammalian enzyme is not known. We provide several lines of
      evidence to suggest that the cAMP-mediated AChE expression in myotube is
      oppositely regulated between avian and mammalian enzymes. Human AChE promoter was
      tagged with luciferase, namely Hp-Luc, which was transfected into cultured chick
      myotubes. Application of cAMP and forskolin induced the expression of chick AChE
      but reduced human AChE promoter-driven luciferase activity. Transfection of cDNAs
      encoding active mutants of G proteins altered the intracellular cAMP level in
      myotubes as well as the expression of chick and human AChE. When the
      constitutively active forms of Activating Transcription Factor-1 (EWS/ATF-1
      oncogene) were over expressed in Hp-Luc transfected myotubes, the expression of
      chick AChE transcript and protein increased from approximately 1.8- to
      approximately 2.5-fold, but the luciferase activity was decreased by over 60%.
      Overexpression of cAMP-responsive element binding protein (CREB) in Hp-Luc
      transfected myotubes markedly enhanced the cAMP-mediated AChE expression in up-
      and downregulated chick and human enzymes, respectively. In addition, CREB bound
      the CRE sequence of human AChE promoter. Mutation on the CRE site markedly
      enhanced the expression of the promoter-driven luciferase; however, its response
      to cAMP inhibition in cultured myotubes was still retained. These findings
      suggest that a cAMP-dependent pathway is contrasting activation and repression of
      AChE expression in chick and human muscles.

PMID- 11312609
TI  - Identification and characterization of CEPU-Se-A secreted isoform of the IgLON
      family protein, CEPU-1.
AB  - CEPU-1/Neurotrimin is a neuronal glycoprotein thought to play a role in axon
      guidance and cell-cell recognition. It is a member of the IgLON family, has three
      C2 domains, and is attached to the plasma membrane by a GPI-anchor. We report
      here the characterisation of an alternatively-spliced isoform of CEPU-1 that is
      secreted. This isoform, termed CEPU-Se, is coexpressed with CEPU-1 in retina,
      cerebellum, and DRG neurons. In the cerebellum CEPU-1/CEPU-Se is expressed
      predominantly on granule cells and in the molecular layer. Divalent but not
      monovalent CEPU-Se interacts with CEPU-1 and other IgLONs, suggesting that the
      ability of CEPU-Se to modify the activity of the IgLON family may require an
      additional cofactor. CEPU-Se does not support the outgrowth of DRG neurons or the
      extension of established growth cones; however, neurite outgrowth on laminin is
      unaffected by CEPU-Se. Our data suggest that CEPU-Se may act to modulate the
      ability of CEPU-1, LAMP, and OBCAM to influence neurite outgrowth.

PMID- 11312610
TI  - Neuregulin signaling through a PI3K/Akt/Bad pathway in Schwann cell survival.
AB  - beta-Neuregulin (betaNRG) is a potent Schwann cell survival factor that binds to
      and activates a heterodimeric ErbB2/ErbB3 receptor complex. We found that NRG
      receptor signaling rapidly activated phosphoinositide 3-kinase (PI3K) in serum
      starved Schwann cells, while PI3K inhibitors markedly exacerbated apoptosis and
      completely blocked NRG-mediated rescue. NRG also rapidly signaled the
      phosphorylation of mitogen-activated protein kinase (MAPK) and the
      serine/threonine kinase Akt. The activation of Akt and MAPK in parallel pathways
      downstream from PI3K resulted in the phosphorylation of Bad at different serine
      residues. PI3K inhibitors that blocked NRG-mediated rescue also blocked the
      phosphorylation of Akt, MAPK, and Bad. However, selective inhibition of MEK
      dependent Bad phosphorylation downstream from PI3K had no effect on NRG-mediated
      survival. Conversely, ectopic expression of wild-type Akt not only enhanced Bad
      phosphorylation but also enhanced autocrine- and NRG-mediated Schwann cell
      survival. Taken together, these results demonstrate that NRG receptor signaling
      through a PI3K/Akt/Bad pathway functions in Schwann cell survival.

PMID- 11312611
TI  - Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP: implications
      for doppel function.
AB  - Ectopic expression of the doppel (Dpl) protein, a homologue of the prion protein
      (PrP), was recently associated with cerebellar Purkinje cell degeneration
      observed in two aging prion protein knock-out (Prnp(0/0)) mouse lines. We
      investigated the possible role of Dpl in oxidative metabolism. Two Prnp(0/0)
      mouse lines of similar genetic background were studied. One line expresses Dpl in
      the brain and displays Dpl-associated cerebellar abnormalities. The other has no
      elevated expression of Dpl and no cerebellar abnormalities. We observed a
      correlation between Dpl expression and the induction of both heme oxygenase 1 (HO
      1) and nitric oxide synthase systems (nNOS and iNOS). These responses are
      suggestive of increased oxidative stress in the brains of the Dpl-expressing
      Prnp(0/0) mice. No induction was observed with Hsp-60, indicating a specific
      response by the HO/NOS system. We proposed that Dpl expression exacerbates
      oxidative damage that is antagonistic to the protective function of wild-type
      PrP.

PMID- 11312612
TI  - Identification of lysine decarboxylase as a mammalian cell growth inhibitor in
      Eikenella corrodens: possible role in periodontal disease.
AB  - The pathogenesis of inflammatory periodontal disease was studied by examining the
      mechanism of HeLa and HL60 cell growth inhibition by cell-free saline-soluble
      extracts of Eikenella corrodens and bacterial plaque. Previous studies identified
      a protein (p80) as causing growth inhibition by E. corrodens extracts. After
      purification by two-dimensional SDS-PAGE, p80 was digested with protease lysC.
      Amino acid sequences were obtained and backtranslated for use as PCR primers. A
      5840 nucleotide sequence containing a lysine decarboxylase gene was obtained from
      a Sau3 A1 genomic library of E. corrodens DNA. Lysine decarboxylase activity was
      present at physiologic pH in the E. corrodens extracts containing p80, and also
      in bacterial plaque. Both extracts caused growth inhibition by depleting lysine
      from cell culture media through conversion to cadaverine. Adding lysine, or
      immune goat IgG to a peptide derived from the active site sequence of E.
      corrodens lysine decarboxylase, retarded lysine depletion and growth inhibition.
      epsilon-Amino caproic acid specifically enhanced lysine decarboxylase activity at
      the low lysine concentration in HL60 cell culture media, and also increased the
      growth inhibition. Thus, lysine decarboxylases such as p80 inhibit growth by
      removing lysine from mammalian cell culture media. A new role for lysine
      decarboxylase activity in the microbial aetiology of periodontal disease is
      discussed.

PMID- 11312613
TI  - Structure-function analysis of Yersinia pestis YopM's interaction with alpha
      thrombin to rule on its significance in systemic plague and to model YopM's
      mechanism of binding host proteins.
AB  - The plague virulence protein YopM of Yersinia pestis KIM5 belongs to the large
      family of leucine-rich repeat (LRR) proteins. The only activity demonstrated so
      far for YopM is thrombin-binding, which could be a function of the small amount
      of YopM that is released into surrounding tissues by the bacteria. This study
      combined deletional and mutational analysis, chemical crosslinking assays, and in
      vitro functional tests with molecular modelling to identify key features of YopM
      necessary for interacting with thrombin. Two Y. pestis strains expressing YopM
      variants that differed in thrombin binding were used to assess the importance of
      thrombin-binding for lethality of plague. Both strains suffered a similar
      decrease in virulence by three orders of magnitude, indicating that thrombin
      binding per se was not the major deficiency for lethality in the systemic disease
      model employed. It remains possible that extracellular YopM could contribute to
      plague pathology and to early events in peripheral tissues. The structural
      studies provided a model for how YopM may interact with thrombin and an insight
      into how YopM's LRR structure may assemble distinct regions for binding different
      targets.

PMID- 11312614
TI  - Aggregation substance-mediated adherence of Enterococcus faecalis to immobilized
      extracellular matrix proteins.
AB  - Aggregation substance (AS) of Enterococcus faecalis (E. faecalis), a sex
      pheromone plasmid encoded cell surface protein, mediates the formation of
      bacterial aggregates, thereby promoting plasmid transfer. The influence of pAD1
      encoded AS, Asa1, on binding to immobilized extracellular matrix proteins was
      studied. The presence of AS increased enterococcal adherence to fibronectin more
      than eight-fold, to thrombospondin more than four-fold, to vitronectin more than
      three-fold, and to collagen type I more than two-fold (P<0.001). In contrast,
      binding to laminin and collagen type IV occurred independently of AS. Adherence
      of the constitutively AS expressing E. faecalis OG1X(pAM721) to immobilized
      fibronectin was found to be approximately five times higher than that of
      Staphylococcus aureus Cowan and approximately 30 times higher than that of
      Streptococcus bovis. Investigation of strains with various deletions within the
      structural gene of asa1 suggests that attachment to immobilized fibronectin is
      mainly mediated by amino acids within the variable region or by neighbouring
      residues. Thus, AS may promote adherence to injured epithelium and endothelium,
      where extracellular matrix proteins are exposed, thereby facilitating
      colonization and infection.

PMID- 11312615
TI  - Molecular cloning, sequence and characterization of cjsT, a putative protease
      from Rickettsia rickettsii.
AB  - The cloning and sequencing of a gene from Rickettsia rickettsii which confers
      haemolytic activity on Escherichia coli strain TB1 is described. The open reading
      frame of the haemolysis-promoting gene, cjsT, is 1041 bp and encodes a putative
      protein with a molecular mass of 33 825 Da. CjsT has high sequence similarity to
      several bacterial proteases, particularly type IV signal peptidases. Cell lysates
      from an E. coli clone containing cjsT in pUC19 (pJON1) exhibited greater protease
      activity in functional assays than found in E. coli containing pUC19 alone.
      Disruption of the cjsT gene by insertional inactivation with a kanamycin cassette
      reduced both the protease and haemolytic activities conferred by cjsT. The
      protease inhibitors antipain and diisopropylfluorophosphate (DFP) both reduced
      the proteolytic activity of pJON1. The mechanism by which the R. rickettsii cjsT
      promotes haemolysis in E. coli remains unclear.

PMID- 11312616
TI  - Immunoglobulin-binding domains of peptostreptococcal protein L enhance vaginal
      colonization of mice by Streptococcus gordonii.
AB  - Protein L, an immunoglobulin-binding protein of some strains of the anaerobic
      bacterium Peptostreptococcus magnus, has been hypothesized to be a virulence
      determinant in bacterial vaginosis. In order to investigate the role of protein L
      in peptostreptococcal virulence, the Ig-binding domains of protein L were
      expressed at the surface of the human oral commensal Streptococcus gordonii.
      Recombinant streptococci were used in vaginal colonization experiments, and
      protein L-expressing S. gordonii demonstrated enhanced ability to colonize the
      vaginal mucosa. Compared to the control strain, they also persisted for a longer
      period in the murine vagina.

PMID- 11312617
TI  - Isolation and characterization of bacteriophage-resistant mutants of Vibrio
      cholerae O139.
AB  - Vibrio cholerae O139 strains produce a capsule which is associated with
      complement resistance and is used as a receptor by bacteriophage JA1. Spontaneous
      JA1-resistant mutants were found to have several phenotypes, with loss of capsule
      and/or O-antigen from the cell surface. Determination of the residual complement
      resistance and infant mouse colonization potential of each mutant suggested that
      production of O-antigen is of much greater significance than the presence of
      capsular material for both of these properties. Two different in vitro assays of
      complement resistance were compared and the results of one shown to closely
      reflect the comparative recoveries of bacteria from the colonization experiments.
      Preliminary complementation studies implicated two rfb region genes, wzz and
      wbfP, as being essential for the biosynthesis of capsule but not O-antigen.

PMID- 11312618
TI  - Thrombin generation and mortality during Staphylococcus aureus sepsis.
AB  - Sepsis-induced abnormalities of coagulation may contribute to mortality during
      severe bacterial infection. The aim of this study was to examine changes in
      coagulation parameters and to assess the role of protein C supplementation during
      murine S. aureus sepsis. Gram-positive sepsis was characterized by a
      hypercoagulable state with predominant activation of the external coagulation
      pathway, registered as an early increase of tissue factor activity and
      concomitant reduction in protein C. The internal coagulation pathway was
      unaffected. No correlation between the changes of coagulation parameters and the
      intensity of inflammation, determined as serum IL-6 levels, was found.
      Supplementation with neither protein C or APC favoured survival in S. aureus
      sepsis. Reduction in thrombin generation in response to protein C supplementation
      was associated with significantly increased survival.

PMID- 11312621
TI  - Preventing vertical HIV transmission in the year 2000: progress and prospects--a
      review.
AB  - In the USA, progress in the ability to eliminate vertical HIV-1 transmission that
      was unthinkable just a few years ago has been virtually achieved with fewer than
      200 new cases of infant HIV infection reported in 1999. Nevertheless, critical
      research questions as well as public health challenges remain. New infant HIV
      infections continue to occur among women who did not obtain prenatal care or who
      were not offered HIV testing during pregnancy and innovative approaches are
      needed to address these barriers. The CDC-funded Mother-Infant Rapid Intervention
      At Delivery (MIRIAD) Study in five US metropolitan areas is one such approach
      that will test the feasibility of offering rapid testing to women presenting late
      in pregnancy or at delivery with undocumented HIV status. In addition, further
      research addressing the role of the placenta in preventing or enhancing in utero
      HIV transmission is needed. Internationally, new clinical trial findings provide
      hope that a short course of antiretrovirals can substantially reduce vertical HIV
      1 transmission in resource-poor settings in the developing world where most
      paediatric HIV infections occur. Future research will focus on the role of post
      perinatal exposure prophylaxis with antiretrovirals administered to the infant
      and on the prevention of postnatal transmission of HIV-1 through breast milk
      while maintaining adequate nutrition. A major challenge is to translate trial
      results into a coordinated public health implementation plan in order to
      maximally reduce mother-to-child HIV-1 transmission worldwide.

PMID- 11312622
TI  - Vertical HIV-1 transmission: prophylaxis and paediatric follow-up.
AB  - OBJECTIVES: To study the effectiveness of anti-HIV therapy for vertical HIV-1
      transmission based on the PACTG protocol 076, modified and adapted to Venezuela.
      METHODS: Between March 1997 and March 2000, 74 HIV-1-infected women (15-42 years
      old) with 77 singleton pregnancies were evaluated. Zidovudine (ZDV) 500 mg/day
      (average 8 weeks) was begun after Western blot confirmatory tests, independent of
      CD4+ count or viral load. ZDV was administered as follows: 47 patients (61 per
      cent) received prenatal, perinatal and postnatal therapy; 13 (17 per cent)
      received prenatal and postnatal therapy; two (3 per cent) received prenatal and
      perinatal therapy; one patient received perinatal and postnatal therapy; seven (9
      per cent) received only postnatal therapy. Seven HIV-1 infected women received no
      treatment. Thirty-two newborns were obtained by C-section (45.7 per cent), while
      38 were delivered vaginally (54.2 per cent). Due to advanced maternal illness,
      seven HIV-1-infected women received ZDV+3TC, two women received ZDV+ddI and one
      woman received ZDV+3TC+ Ritonavir. Breastfeeding was avoided in all cases.
      RESULTS: Outcomes showed 65 term newborns and five preterm newborns; three
      abortions; one fetal loss and one preterm death. Two maternal/fetal deaths were
      secondary to complications related to AIDS at 27 and 29 weeks, respectively.
      Twenty-one children over 18 months old were considered uninfected. Thirty-five
      infants below 15 months of age were considered with the status of indeterminate
      HIV-1 infection (PO). Three infants fewer than 5 months of age with multiple risk
      factors were considered infected (P2). Two infants were asymptomatic and HIV
      positive at 12 months of age (P1). Eight children were lost to follow-up.
      CONCLUSIONS: Independent of maternal status and delivery type, confirmed vertical
      transmission of HIV-1-infected women who received ZDV is 4.25 per cent. Prenatal
      care with a multidisciplinary team is necessary for good obstetric and newborn
      outcomes.

PMID- 11312623
TI  - DC-SIGN, a dentritic cell-specific HIV-1 receptor present in placenta that
      infects T cells in trans-a review.
AB  - Dendritic cells (DC) capture micro-organisms that enter peripheral mucosal
      tissues and then migrate to secondary lymphoid organs, where they present in
      antigenic form to resting T cells and thus initiate adaptive immune responses.
      Here we describe the properties of a DC-specific C-type lectin, DC-SIGN, that is
      highly expressed on DC present in mucosal tissues and binds to the HIV-1 envelope
      glycoprotein gp120. DC-SIGN does not function as a receptor for viral entry into
      DC, but instead promotes efficient infection in trans of cells that express CD4
      and chemokine receptors. The interaction of DC-SIGN with HIV gp120 may be an
      important target for therapeutic intervention and vaccine development.

PMID- 11312624
TI  - Chemokine receptor expression by human syncytiotrophoblast--a review.
AB  - Knowledge of chemokine receptor expression by human syncytiotrophoblast has
      important implications for our understanding of maternal-fetal HIV transmission
      as well as for understanding the regulation of placental growth and development.
      This review discusses what is known about chemokine receptor expression by
      trophoblast and other placental cells. In addition, new data are presented
      showing that CXCR4 is expressed on the syncytiotrophoblast surface. In other new
      studies, leukocyte-mediated HIV-1Lai(an X4 strain) infection of
      syncytiotrophoblast cultures was reduced when stromal derived factor-1alpha was
      added to the cocultures, consistent with a role for CXCR4. The available
      information on chemokine receptor expression by trophoblast is discussed in terms
      of the apparent selective transmission of R5 strains. Studies in other systems
      indicate that caution must be used in predicting chemokine receptor usage by
      different HIV isolates, particularly when the route of infection is cellmediated.

PMID- 11312625
TI  - Expression of the HIV-1 co-receptors CCR5 and CXCR4 on placental macrophages and
      the effect of IL-10 on their expression.
AB  - The chemokine receptors CCR5 and CXCR4 play a key role in HIV-1 infection as co
      receptors for viral entry. In the placenta, an important natural barrier to HIV,
      the expression and regulation of these receptors has yet to be elucidated. In
      this study, we determined the expression of CCR5 and CXCR4 co-receptors on
      placental macrophages (PM) and the effect of interleukin-10 (IL-10) on co
      receptor expression. PM were isolated from term placentae of HIV-uninfected
      mothers and cultured for up to 11 days. The cells were stimulated with IL-10 for
      24 h and stained with specific antibodies to CCR5, CXCR4, CD4, CD3, CD11c and
      CD14 for flow cytometry. Unstimulated PM expressed significantly more CCR5 than
      CXCR4. Expression of both co-receptors was upregulated by stimulation with IL-10
      at 24 h post-stimulation. In vivo expression of these co-receptors from frozen
      sections revealed a higher percentage of CCR5 positive cells. This is the first
      study in which expression of both co-receptors is detected on the PM membrane.
      These results are consistent with previous studies performed in our laboratory
      where PM were readily infected by CCR5-using HIV strains but could not be
      productively infected by HIV strains that exclusively use CXCR4 as a co-receptor.

PMID- 11312626
TI  - Perinatal infections: HIV and co-infections in the placenta and therapeutic
      interventions-a workshop report.

PMID- 11312627
TI  - Reactive oxygen species and preterm premature rupture of membranes-a review.
AB  - Preterm premature rupture of membranes (PPROM) results initially from damage to
      collagen in the chorioamnion leading to a tear in the membrane. Tissue-damaging
      molecules called reactive oxygen species (ROS) are capable of damaging collagen
      in the chorioamnion that could lead to PPROM. This hypothesis is supported by
      epidemiological studies linking clinical conditions known to produce ROS or
      reduce antioxidant protection to PPROM, by in-vitro studies in which membrane
      segments exposed to ROS exhibited tissue alterations consistent with PPROM, and
      by clinical studies showing that chorioamnion and amniotic fluid samples obtained
      from PPROM patients exhibit excessive collagen degradation. The role of
      antioxidants to protect the chorioamnion from ROS damage has been demonstrated in
      one in-vitro study. A prospective, randomized blinded trial of antioxidant
      therapy during pregnancy is needed to evaluate this approach for the prevention
      of PPROM.

PMID- 11312628
TI  - Effect of hypoxia, oxidative stress and lipopolysaccharides on the release of
      prostaglandins and cytokines from human term placental explants.
AB  - Placental hypoxia, ischaemia, reperfusion and resultant oxidative stress, with
      the release of various factors into the maternal vasculature acting as mediators
      of endothelial cell dysfunction, play an important role in the development of pre
      eclampsia. Human term placental tissue explants were exposed to different
      stressors, e.g. hypoxia, oxidative stress and lipopolysaccarides, and the effect
      on the release of prostanoids and cytokines was determined. The hypoxic
      environment consisted of 2 per cent O2, 5 per cent CO2and 93 per cent N2.
      Oxidative stress was induced by addition of xanthine together with xanthine
      oxidase to the incubation medium. As a third experimental variable,
      lipopolysaccharide was added to the medium. Prostaglandins (8-iso-PGF(2alpha), or
      6-keto-PGF(1alpha)and TXB(2)as stable metabolites of prostacyclin and
      thromboxane, respectively) and cytokines (TNF-alpha, IL-1alpha, IL-1beta, IL-6)
      were measured using commercial ELISA assays. Under control conditions, the
      production of prostaglandins in ng/24 h (mean +/- s.d.) was 6 +/- 3 for 8-iso
      PGF(2alpha), 19 +/- 9 for 6-keto-PGF(1alpha)and 5 +/- 2 for TXB2. The production
      of cytokines was 13 +/- 6 pg for TNF-alpha, 7 +/- 2 pg for IL-1alpha, 5 +/- 3 pg
      for IL-1beta and 18 +/- 9 ng for IL-6. Under hypoxia the production of
      prostaglandins remained unchanged and of the cytokines only IL-1beta showed a 15
      fold increase. Oxidative stress resulted in an increase in the release of
      prostaglandins and of cytokines of 4- to 15- and 3- to 130-fold, respectively.
      Lipopolysaccharides and oxidative stress had a similar effect on the production
      of prostaglandins, whereas the stimulatory effect of lipopolysaccharides on
      cytokines was significantly higher than that of oxidative stress.

PMID- 11312629
TI  - Does nitric oxide play a role in the aetiology of pre-eclampsia?
AB  - Although progress has been made toward our understanding of the pathophysiology
      of pre-eclampsia, the precise aetiology of this disease still remains an enigma.
      One of the hallmarks of pre-eclampsia is a failure of the extravillous
      cytotrophoblast cells to invade and remodel the uterine spiral arterioles during
      the first trimester of pregnancy. Moreover, studies suggest that the cause of
      this disorder may be immunological in nature. Evidence is provided here
      suggesting that impaired trophoblastic invasion of the spiral arterioles may be
      linked to the altered immunological response associated with pre-eclampsia.
      Previous studies by Reister et al., 1999 demonstrated a direct relationship
      between macrophage infiltration of the myometrial segments of spiral arterioles
      and reduced trophoblastic invasion in pre-eclampsia. Also, it is well established
      that activated macrophages produce large amounts of nitric oxide (NO). Our
      present findings reveal that low concentrations of NO-mimetic drugs (glyceryl
      trinitrate and sodium nitroprusside) inhibit the ability of trophoblast cells to
      penetrate through reconstituted extracellular matrix (Matrigel). This inhibition
      is accompanied by a reduced expression of the cell surface urokinase receptor, a
      molecule important for invasion. These results suggest a possible mechanistic
      link between the aberrant macrophage infiltration associated with pre-eclampsia,
      and the maladapted uteroplacental arterioles that characterize the disease.

PMID- 11312630
TI  - Nitrotyrosine immunostaining correlates with increased extracellular matrix:
      evidence of postplacental hypoxia.
AB  - Nitrotyrosine residues (NT), an index of oxidative stress arising from
      peroxynitrite formation and action, are found in placental vasculature of
      pregnancies complicated by pre-eclampsia (PE) or pregestational insulin-dependent
      diabetes mellitus (IDDM). This study correlates conventional placental pathology
      with NT immunostaining in 20 cases of perinatal mortality (13 stillbirths and
      seven cases of neonatal mortality) associated with PE, IDDM, amniotic fluid
      infection syndrome (AFIS), or from fetal/neonatal demise not related to these
      conditions (congenital anomalies) (n = five/group). Patients with PE have more
      decidual arteriolopathy and Tenney-Parker change, while patients with IDDM and
      ascending infection have more villous cytotrophoblastic hyperplasia. Archival
      paraffin-embedded placental sections were immunostained for NT for correlation
      with clinical features and H&E histological findings. The intensity of
      immunostaining for NT varied from absent (n = 7) to 1+ (n = 5) or 2+ (n = 8). All
      eight placentae with 2+ staining showed increased villous extracellular matrix
      (ECM), compared to none of five with 1+ staining and two of seven with no
      staining (chi2 = 14.3, P = 0.001). There was no statistically significant
      difference in the percentage of stem villi with luminal vascular abnormalities
      (5.7 vs 10 vs 35.7 per cent, F = 2.3, P = 0.1). Our data show that increased
      production of reactive oxygen species by placental tissue may be associated with
      increased extracellular matrix, itself produced by fibroblasts under the
      influence of oxygen. NT immunostaining may therefore help differentiate those
      cases of perinatal morbidity/mortality associated with post-placental hypoxia
      provided that the secondary impact of intrauterine fetal death can be excluded by
      future studies.

PMID- 11312631
TI  - Hypoxia: implications for implantation to delivery-a workshop report.

PMID- 11312632
TI  - Angiogenesis and blood flow: implications for pathobiology--a workshop report.

PMID- 11312633
TI  - Trophoblastic neoplasia--a workshop report.

PMID- 11312634
TI  - Nutrition of the human fetus during the first trimester--a review.
AB  - In all mammalian species nutrition of the conceptus is initially histiotrophic,
      with the trophectoderm phagocytosing first oviductal and then uterine secretions.
      Following implantation and establishment of the chorioallantoic placenta there is
      a transition to haemotrophic nutrition, with exchange between the maternal and
      fetal circulations. It has long been assumed that the transition occurs soon
      after implantation in the human, due to the invasive nature of this process.
      However, the recent realization that the maternal circulation to the placenta is
      not fully established until the end of the first trimester casts doubt on the
      validity of this assumption. There is new evidence that the uterine glands
      discharge secretions into the intervillous space until at least 8 weeks of
      pregnancy, and that these are taken up by the syncytiotrophoblast. Also, during
      early pregnancy selected maternal proteins accumulate within the fluid of the
      coelomic cavity, from which they may be transported to the fetus by the secondary
      yolk sac. Histiotrophic nutrition may be advantageous to the fetus during the
      first trimester as it provides nutrients under a low oxygen concentration, so
      reducing the risk of free radical mediated damage during the sensitive period of
      organogenesis. Once this is complete, and fetal oxygen requirements rise, there
      is a transition to haemotrophic nutrition at the start of the second trimester,
      when the maternal placental circulation is fully established.

PMID- 11312635
TI  - Altered placental structure induced by maternal food restriction in guinea pigs:
      a role for circulating IGF-II and IGFBP-2 in the mother?
AB  - Maternal feed restriction may restrict fetal growth in part indirectly by
      impairing placental functional development. Such actions could be mediated by the
      insulin-like growth factors (IGF), which are important modulators of placental
      growth and differentiation and more generally, are influenced by nutrient
      availability. While a role for the fetal IGF axis has been demonstrated, less is
      known of the influence, if any, of that in the mother. This study aimed to
      determine whether alterations in the maternal IGF axis and placental functional
      and structural development due to maternal food restriction are related. We
      therefore examined the associations between placental structural parameters, the
      ratios of maternal to fetal plasma glucose and fetal to maternal plasma urea
      concentration, and maternal circulating IGF-I, IGF-II and IGFBP-2 in ad libitum
      fed and food restricted (70-90 per cent of the ad libitum intake) pregnant guinea
      pigs. In mid-gestation, fetal weight (r = 0.65, P = 0.008, n = 17), volume of the
      maternal blood space (r = 0.58, P = 0.048, n = 17), and surface density of
      syncytiotrophoblast (r = 0.65, P = 0.023, n = 17), were positively correlated,
      and syncytiotrophoblast thickness was negatively correlated, with maternal plasma
      IGF-II concentration (r = -0.69, P = 0.014, n = 17). Late in gestation, fetal
      weight, placental weight and total exchange surface area in the placenta were
      each negatively correlated with maternal plasma IGFBP-2 concentration (all P <
      0.01), while the arithmetic mean thickness of syncytiotrophoblast was positively
      correlated with maternal plasma IGFBP-2 concentration. Late in gestation, the
      ratio of maternal to fetal plasma glucose was positively correlated with fetal
      weight (r = 0.54, P = 0.038, n = 15) and the ratio of fetal to maternal plasma
      urea concentration was positively correlated with placental weight (r = 0.52,
      P=0.046, n=15). Maternal feed restriction reduced the ratio of maternal plasma
      IGF-II to IGFBP-2 in late gestation by 75 per cent (P = 0.001) and this ratio was
      positively correlated with fetal weight (r = 0.56, P = 0.01, n = 20), placental
      weight (r = 0.59, P = 0.006), placental diameter (r = 0.621, P = 0.003),
      placental volume (r = 0.57, P=0.009), weight of trophoblast (r = 0.51, P=0.037),
      weight of fetal capillaries (r = 0.49, P = 0.046), syncytiotrophoblast surface
      density (r = 0.611, P = 0.009) and negatively correlated with syncytiotrophoblast
      thickness (r = -0.55, P = 0.021). Our results suggest that in mid-pregnancy,
      maternal circulating IGF-II promotes placental structural development, while
      later in pregnancy, IGFBP-2 inhibits it, and their relative abundance and
      interaction strongly influences placental structure and function near term.

PMID- 11312636
TI  - Key regulatory transcription factors involved in placental trophoblast
      development--a review.
AB  - Specification of the trophoblast cell lineage comprising the outermost epithelial
      cell layer of the blastocyst occurs early in development and is a prerequisite
      for implantation of the embryo and subsequent formation of the placenta, a
      multifunctional organ which is indispensable for the proper development of the
      fetus. Trophoblast stem cells of the placenta give rise to distinct highly
      differentiated trophoblast subtypes which build the functional units of the
      organ. These specialized cells assure anchorage of the embryo to the mother,
      establishing a vascular connection transporting nutrients and gases and
      expression of hormones that are required for the successful progression of
      pregnancy. Developmental processes of the trophoblast occur in a spatially and
      temporally highly organized manner. Despite these facts, little is known on the
      key regulatory factors which commit and differentiate trophoblast cells in
      humans. Recent studies in mice, however, provided evidence that various cell-type
      specific transcription factors play crucial roles in the developmental programme
      of the trophoblast. In this review we will focus on the function of these major
      regulatory factors in murine trophoblast/placental development and discuss the
      potential role of their homologues in the human system.

PMID- 11312637
TI  - Defect of syncytiotrophoblast formation and human chorionic gonadotropin
      expression in Down's syndrome.
AB  - The syncytiotrophoblast (ST) is a major component of the human placenta as it is
      involved in feto-maternal exchanges and the secretion of pregnancy-specific
      hormones. We have studied the formation and function of the ST in normal and
      trisomy 21 (T21)-affected placenta using the in vitro model of cytotrophoblast
      differentiation into ST. Cytotrophoblast cells were isolated from first
      trimester, second trimester and term placentae. In vitro cytotrophoblast cells
      isolated from normal placenta fused to form the ST. This was associated with an
      increase in the transcript levels and the secretion of human chorionic
      gonadotropin (hCG). However, the secretion of hCG decreased through pregnancy. In
      T21-affected placentae, we observed a defect (or a delay) in ST formation and a
      dramatic decrease in the synthesis and secretion of this hormone compared with
      cultured cells isolated from control age-matched placentae. These results were
      confirmed by a significant (P < 0.05) decrease in transcript levels of alpha and
      beta subunits of hCG in total homogenates of T21-affected placentae compared with
      controls. These results suggest a decrease in functional mass of ST in T21
      placenta, and therefore a decrease in production of placental pregnancy-specific
      polypeptide hormones.

PMID- 11312638
TI  - Signal transductions: variants on developmental control from implantation to
      delivery--a workshop report.

PMID- 11312639
TI  - Apoptosis: molecular control of placental function--a workshop report.

PMID- 11312640
TI  - Cell culture models of human trophoblast II: trophoblast cell lines--a workshop
      report.

PMID- 11312641
TI  - Cell culture models of human trophoblast: primary culture of trophoblast--a
      workshop report.

PMID- 11312643
TI  - Effect of hypophysectomy and growth hormone replacement on the modulation of p450
      expression after treatment with the aromatic hydrocarbon ethylbenzene.
AB  - Pituitary status has a significant effect on the expression of several cytochrome
      P450 enzymes. The goal of this study was to examine the role of pituitary input
      on the modulation of CYP2C11 and CYP2B after treatment with the aromatic
      hydrocarbon ethylbenzene (EB). Intact, hypophysectomized (HX), and HX rats
      supplemented with pulsatile growth hormone (GH) were treated with corn oil or EB
      and the effects on hepatic P450 expression were determined. Hypophysectomy caused
      a 50% decrease in CYP2C11 protein in untreated rats, whereas GH supplementation
      returned protein to control levels. EB administration also decreased CYP2C11
      protein in intact rats; however, this decrease was not observed after EB
      treatment in HX or HX + GH groups. CYP2C11-dependent testosterone 2alpha
      hydroxylation followed a similar pattern as CYP2C11 protein, except that the
      activity was only partially restored by GH replacement. CYP2B levels were also
      substantially influenced by hypophysectomy. Intact rats exhibited a 100-fold
      increase in CYP2B1 mRNA, reaching a maximum 12 h after EB administration. A much
      smaller response (ca. 20-fold) was observed in HX rats, reaching a maximum 24 h
      after EB treatment. This effect was not reversed by GH supplementation. The half
      life for EB was significantly increased from 8 h in intact rats to 14 h in HX
      rats, suggesting higher plasma EB concentrations after EB administration to HX
      rats. These results indicate that CYP2C11 and CYP2B become less responsive to EB
      dependent modulation in HX rats, a response that cannot be explained simply by
      absence of GH or by altered EB pharmacokinetics in HX animals.

PMID- 11312644
TI  - Characterization of T cell responses to fragrances.
AB  - Fragrances are worldwide a major cause of allergic contact dermatitis (ACD), a
      delayed-type hypersensitivity reaction mediated by T lymphocytes. We investigated
      T cell responses to fragrances using peripheral blood mononuclear cells (PBMC)
      and T cells from skin lesions of fragrance-allergic patients. The components of a
      fragrance mixture (eugenol, isoeugenol, geraniol, oak moss, alpha-amyl cinnamic
      aldehyde, cinnamic aldehyde, cinnamic alcohol, and hydroxycitronellal) that is
      commonly used in the patch test were studied in vitro in the lymphocyte
      transformation test (LTT). PBMC from fragrance-allergic patients (n = 32) showed
      significant stimulations to all eight fragrances. The calculated stimulation
      indices (SI) varied between 2.1 and 21.8. The influence of metabolic enzymes on T
      cell stimulation was studied for two fragrances. Interestingly, stimulation of
      eugenol and isoeugenol was increased in the presence of antigen-modified human
      liver microsomes (CYP450) or recombinant CYP1A1 in five of seven cases.
      Furthermore, we established 18 T cell clones (TCC) from a skin lesion reacting
      specifically to eugenol. FACS analysis revealed that the majority (n = 15, 83%)
      of TCC were CD3(+), CD4(+), and HLA-DR(+). Seventeen percent (n = 3) of the
      clones were CD8(+). TCC (n = 4) released significant amounts of IL-2 and IFN
      gamma but no IL-4 and IL-5. In addition, CD4(+) TCC (n = 3) showed antigen
      induced cytotoxic activities against autologous B cells. In summary, we
      demonstrated for the first time that fragrance-specific CD4(+) and CD8(+) T
      lymphocytes are present in fragrance-allergic individuals. In addition, our
      results suggest that CYPs can be involved in the formation of the nominative
      antigen.

PMID- 11312645
TI  - Interaction of formamidine pesticides with the presynaptic alpha(2)-adrenoceptor
      regulating.
AB  - The effects of the formamidine pesticides amitraz and chlordimeform on the
      alpha(2)-adrenergic receptor subtype that mediates the release of
      [(3)H]noradrenaline by synaptosomes from rat hypothalami were studied. We
      initially characterized the presynaptic autoreceptor on noradrenergic nerve
      endings using selective antagonists. Yohimbine (a nonselective alpha(2)
      antagonist) and BRL 44408 (selective for subtypes alpha(2A)/alpha(2D)) diminished
      the inhibitory effect of xylazine on K(+)-evoked release of [(3)H]noradrenaline;
      the K(B) values were 481 and 154 nM, respectively. In contrast, prazosin (a
      selective alpha(2B)/alpha(2C) antagonist) did not modify the inhibitory effect of
      xylazine. These results indicate that the release of noradrenaline by
      noradrenergic nerve endings in the rat hypothalamus is regulated by alpha(2D)
      adrenoceptors, a species variation of the human alpha(2A) subtype. We then
      assessed the effects of the two pesticides on the K(+)-evoked release of
      [(3)H]noradrenaline. Amitraz reduced release in a dose-dependent manner; the
      effect observed at the maximal concentration tested (10 microM) was 13.0 +/- 2.0%
      and it was reversed by yohimbine. Amitraz also diminished the inhibitory effects
      of the alpha(2)-adrenergic agonists clonidine and xylazine. Chlordimeform
      displayed no effects, possibly because the true active compound of this
      insecticide is its demethylated metabolite. Based on these findings we conclude
      that the formamidine pesticides act as partial agonists of presynaptic alpha(2D)
      adrenergic receptors in the rat hypothalamus. This interaction may be responsible
      for the in vivo alterations in catecholaminergic regulation of cyclic variations
      in gonadotropin-releasing hormone (GnRH) secretion, which can have grave
      functional repercussions on the reproductive system of mammals exposed to these
      xenobiotics.

PMID- 11312646
TI  - Propanil inhibits tumor necrosis factor-alpha production by reducing nuclear
      levels of the transcription factor nuclear factor-kappab in the macrophage cell
      line ic-21.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an essential proinflammatory cytokine
      whose production is normally stimulated by bacterial cell wall components, such
      as lipopolysaccharide (LPS), during an infection. Macrophages stimulated with LPS
      in vitro produce several cytokines, including TNF-alpha. LPS-stimulated primary
      mouse macrophages produced less TNF-alpha protein and message after treatment
      with the herbicide propanil (Xie et al., Toxicol. Appl. Pharmacol. 145, 184-191,
      1997). Nuclear factor-kappaB (NF-kappaB) tightly regulates TNF-alpha
      transcription. Therefore, as a step toward understanding the mechanism of the
      effect of propanil on TNF-alpha transcription, IC-21 cells were transfected with
      a TNF-alpha promoter-luciferase construct, and the effect of propanil on
      luciferase activity was measured. Cells transfected with promoter constructs
      containing a kappaB site showed decreased luciferase activity relative to
      controls after propanil treatment. These observations implicated NF-kappaB
      binding as an intracellular target of propanil. Further studies demonstrated a
      marked reduction in the nuclear levels of the stimulatory p65 subunit of NF
      kappaB after propanil treatment, as measured by fluorescence confocal microscopy
      and Western blot analysis. The p50 subunit of NF-kappaB was not found to be
      reduced after propanil exposure by Western blot. Electrophoretic mobility gel
      shift assays showed decreased DNA binding of both p65/p50 heterodimers and
      p50/p50 homodimers to the kappaB3 site of the TNF-alpha promoter of propanil
      treated cells. The marked reduction in nuclear p65/p50 NF-kappaB levels and
      diminished binding to the TNF-alpha promoter in propanil-treated cells are
      consistent with reduced TNF-alpha levels induced by LPS.

PMID- 11312647
TI  - The effects of phencyclidine pretreatment on cocaine-mediated hepatotoxicity in
      mice.
AB  - Cocaine-mediated hepatotoxicity (CMH) requires cocaine (CCN) bioactivation by
      microsomal monooxygenase enzymes that results in cell death. Proposed mechanisms
      of toxicity involve reactive metabolites that covalently bind to hepatocellular
      proteins, depletion of cellular reducing equivalents through redox cycling,
      and/or the generation of reactive oxygen and nitrogen species that alter lipids
      and proteins. We have previously shown that phencyclidine (PCP) pretreatment
      potentiated CMH in CF-1 mice without increasing in vitro N-demethylation or N
      hydroxylation of CCN. We have now further characterized PCP-potentiated CMH and
      determined that it is a dose- and time-dependent process, with PCP doses as low
      as 2.5 mg/kg for 3 days significantly increasing CMH. Immunohistochemistry and
      histology of livers from mice pretreated with PCP before CCN administration
      revealed a marked correlation between the regions of CCN metabolite binding and
      that of necrosis, whereas there was little binding or necrosis in vehicle
      pretreated mice. Although hepatic GSH levels were not altered after repetitive
      PCP treatment alone, a sustained decrease (at least 6 h) in these levels was
      observed following CCN administration. Inhibitors of inducible nitric oxide
      synthase (NOS) abrogated PCP-potentiated CMH, although repetitive PCP treatment
      alone did not increase nitric oxide synthesis systemically or locally in hepatic
      tissue nor did lipopolysaccharide induction of NOS (without PCP) directly
      potentiate CMH. The precise mechanisms of PCP potentiation of CMH and involvement
      of NOS in CMH remain unclear, however, sustained depletion of GSH levels and
      increased hepatocellular binding of reactive cocaine metabolites have been
      demonstrated.

PMID- 11312648
TI  - Inhibition of lysyl hydroxylase by malathion and malaoxon.
AB  - The inhibition of lysyl hydroxylation in newly synthesized collagen by malathion
      and its oxidation product malaoxon were studied with cultured rat fetal lung
      fibroblasts. Exposure of these cells to 125 microM malathion or malaoxon for 96 h
      resulted in a 25 and a 30% decrease in the ratio of hydroxylated lysine/lysine
      residues, respectively, in acid hydrolyzed cell lysates compared to control
      values. This relative decrease in hydroxylysine was not caused by cytotoxicity or
      changes in total collagen content, which were found to remain constant as
      measured by Alamar Blue metabolism and Sircol dye binding assays. Direct
      inhibition of lysyl hydroxylase by malathion and malaoxon was observed using an
      in vitro enzyme assay with recombinant lysyl hydroxylase with a baculoviral
      system. The IC50 values for malathion and malaoxon were estimated to be
      approximately 60 and 45 microM, respectively. These observed IC50 values are
      consistent with calculated values for the intracellular concentration of
      malathion in the cell culture experiments. These results support a significant
      role for inhibition of lysyl hydroxylase activity as causing, or contributing to,
      the teratogenic effects of malathion and malaoxon.

PMID- 11312649
TI  - Gaseous nitric oxide-induced 8-nitroguanine formation in human lung fibroblast
      cells and cell-free DNA.
AB  - A time- and dose-dependent increase in 8-nitroguanine (8-NO(2)-G) was observed in
      human lung fibroblast cells (MRC-5) after treatment with gaseous NO-saturated
      buffer. It was also found that treatment with the inhibitor of inducible nitric
      oxide synthase (iNOS), N(G)-nitro-l-arginine methyl ester, significantly reduced
      the 8-NO(2)-G level in the gaseous NO-saturated buffer-treated MRC-5 cells. These
      results provide evidence indicating that NO gas causes DNA damage in mammalian
      cells, which involves the activation of iNOS and the subsequent generation of
      endogenous NO. On the other hand, a time- and dose-dependent increase in 8-NO(2)
      G was also observed while DNA (isolated from MRC-5 cells) was incubated with
      gaseous NO-saturated buffer. These results suggest that part of the 8-NO(2)-G
      formation was due to direct modification of gaseous NO on DNA. Furthermore, an
      increase in nitrite concentration was found in both cell-free and MRC-5 cell
      conditioned medium treated with gaseous NO-saturated buffer. Collectively,
      gaseous NO induced DNA damage by forming 8-NO(2)-G, a modification performed
      directly by the treated gaseous NO and indirectly by the following induction of
      endogenous NO. This effect might be an important pathway in genotoxicity of
      nitric oxides, and 8-NO(2)-G could act as a specific marker for DNA damage
      induced by gaseous NO, a common contaminatant in air pollution and cigarette
      smoke.

PMID- 11312650
TI  - Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and
      estradiol production in cultured rat granulosa cells.
AB  - The female reproductive toxicity of di-(2-ethylhexyl) phthalate and its active
      metabolite mono-(2-ethylhexyl) phthalate (MEHP) is attributed to suppression of
      ovarian granulosa cell estradiol production. In these studies, several
      structurally related phthalates (0-200 microM) and Wy-14,643 (0-100 microM) were
      compared to MEHP for their effects on granulosa cell estradiol production and
      transcript levels of cytochrome P450 enzyme CYP 19, also known as aromatase
      (P450arom), the rate-limiting enzyme in the conversion of androgens to estrogens.
      Granulosa cells were obtained from 28-day-old Fisher 344 rats and were cultured
      for 48 h. Test chemical or DMSO was added at the time of culture, along with
      testosterone as a substrate for aromatase. 17beta-Estradiol production was
      measured by standard radioimmunoassay, mRNA was measured by fluorescent RT-PCR,
      and protein was measured by Western blot analysis. MEHP was unique among the
      phthalates in its ability to decrease estradiol production, while Wy-14,643 had
      effects similar to MEHP at 100 microM. MEHP and Wy-14,643 also significantly
      decreased aromatase mRNA levels. The decrease in mRNA was concentration dependent
      and was paralleled by a decrease in aromatase protein. MEHP did not alter levels
      of CYP 11A1, the cholesterol side-chain cleavage enzyme (P450scc). Treatment with
      a cAMP analogue increased expression of P450scc in the presence of MEHP (100 to
      200 microM) while the decrease in aromatase remained. Thus, these studies suggest
      that MEHP is distinct from several structurally related phthalates but similar to
      the peroxisome proliferator Wy-14,643 in its action on granulosa cell estradiol
      production. Moreover, the suppression of estradiol by MEHP is likely mediated
      through its action on aromatase transcript levels independent of cAMP-stimulated
      regulation.

PMID- 11312651
TI  - Differential effects of trivalent and pentavalent arsenicals on cell
      proliferation and cytokine secretion in normal human epidermal keratinocytes.
AB  - There is strong evidence from epidemiologic studies of an association between
      chronic exposure to inorganic arsenic (iAs) and hyperpigmentation,
      hyperkeratosis, and neoplasia in the skin. Although it is generally accepted that
      methylation is a mechanism of arsenic detoxification, recent studies have
      suggested that methylated arsenicals also have deleterious biological effects. In
      these studies we compare the effects of inorganic arsenicals (arsenite (iAs(III))
      and arsenate (iAs(V))) and trivalent and pentavalent methylated arsenicals
      (methylarsine oxide (MAs(III)O), complex of dimethylarsinous acid with
      glutathione (DMAs(III)GS), methylarsonic acid (MAs(V)), and dimethylarsinic acid
      (DMAs(V))) in human keratinocyte cultures. Viability testing showed that the
      relative toxicities of the arsenicals were as follows: iAs(III) > MAs(III)O >
      DMAs(III)GS > DMAs(V) > MAs(V) > iAs(V). Trivalent arsenicals induced an increase
      in cell proliferation at concentrations in the 0.001 to 0.01 microM range, while
      at high concentrations (>0.5 microM) cell proliferation was inhibited.
      Pentavalent arsenicals did not stimulate cell proliferation. As seen in the
      viability studies, the methylated forms of As(V) were more cytotoxic than iAs(V).
      Exposure to low doses of trivalent arsenicals stimulated secretion of the growth
      promoting cytokines, granulocyte macrophage colony stimulating factor and tumor
      necrosis factor-alpha. DMAs(V) reduced cytokine secretion at concentrations at
      which proliferation and viability were not affected. These data suggest that
      methylated arsenicals, products of the metabolic conversion of inorganic arsenic,
      can significantly affect viability and proliferation of human keratinocytes and
      modify their secretion of inflammatory and growth-promoting cytokines.

PMID- 11312652
TI  - Role of human GABA(A) receptor beta3 subunit in insecticide toxicity.
AB  - The gamma-aminobutyric acid type A (GABA(A)) receptor is the target for the major
      insecticides alpha-endosulfan, lindane, and fipronil and for many analogs. Their
      action as chloride channel blockers is directly measured by binding studies with
      [(3)H]ethynylbicycloorthobenzoate ([(3)H]EBOB). This study tests the hypothesis
      that GABA(A) receptor subunit composition determines the sensitivity and
      selectivity of insecticide toxicity. Human receptor subtypes were expressed
      individually (alpha1, alpha6, beta1, beta3, and gamma2) and in combination in
      insect Sf9 cells. Binding parameters were similar for [(3)H]EBOB in the beta3
      homooligomer, alpha1beta3gamma2 heterooligomer, and native brain membranes, but
      toxicological profiles were very different. Surprisingly, alpha-endosulfan,
      lindane, and fipronil were all remarkably potent on the recombinant beta3
      homooligomeric receptor (IC50 values of 0.5-2.4 nM), whereas they were similar in
      potency on the alpha1beta3gamma2 subtype (IC50 values of 16-33 nM) and highly
      selective on the native receptor (IC50 values of 7.3, 306, and 2470 nM,
      respectively). The selectivity order for 29 insecticides and convulsants as IC50
      ratios for native/beta3 or alpha1beta3gamma2/beta3 was as follows: fipronil >
      lindane > 19 other insecticides including alpha-endosulfan and picrotoxinin > 4
      trioxabicyclooctanes and dithianes (almost nonselective) >
      tetramethylenedisulfotetramine, 4-chlorophenylsilatrane, or alpha-thujone.
      Specificity between mammals and insects at the target site (fipronil > lindane >
      alpha-endosulfan) paralleled that for toxicity. Potency at the native receptor is
      more predictive for inhibition of GABA-stimulated chloride uptake than that at
      the beta3 or alpha1beta3gamma2 receptors. Therefore, the beta3 subunit contains
      the insecticide target and other subunits differentially modulate the binding to
      confer compound-dependent specificity and selective toxicity.

PMID- 11312653
TI  - Role of oxidative stress and antioxidant defense in 3,3',4,4',5
      pentachlorobiphenyl-induced toxicity and species-differential sensitivity in
      chicken and duck embryos.
AB  - The role of oxidative stress and antioxidant defense in 3,3',4,4',5
      pentachlorobiphenyl (PCB 126)-induced toxicity and species-specific sensitivity
      was examined in White Leghorn chicken (Gallus domesticus) and Pekin duck (Anas
      platyrhynchos) embryos. Eggs were injected into the air cell with 0.4-1.6
      microgram PCB 126/kg egg in corn oil prior to incubation. Lipid peroxidation
      measured by thiobarbituric acid reactive substances (TBARS), the GSSG:GSH ratio,
      and glutathione peroxidase (GPox) activities were determined in liver and adipose
      tissue of day 19 chicken and day 26 duck embryos. In chicken embryos, PCB 126
      increased mortality and the incidence of edema and liver lesions, decreased
      embryo size, increased eye and head malformations, and markedly reduced fat
      storage. In contrast, no effects on the endpoints were observed in duck embryos
      even at the highest dose used in chicken embryos. PCB 126 increased hepatic 7
      ethoxyresorufin-O-deethylase (EROD) activity in a dose-dependent manner in
      chicken but not duck embryos. PCB 126 significantly increased TBARS levels in
      liver and to a greater degree in adipose tissue of chicken embryos, indicating
      that adipose tissue is a sensitive target for this compound. Increases in lipid
      peroxidation by PCB 126 were associated with significant decreases in GPox
      activity in these tissues. These biochemical changes support oxidative stress
      playing a role in PCB 126-induced embryo toxicity while antioxidant defenses
      provided protection against oxidative damage induced by this compound. Ducks, the
      less-sensitive species, showed higher basal levels of hepatic GPox than chickens,
      suggesting that this antioxidant enzyme may contribute to the differences in
      sensitivity to this compound between the two species.

PMID- 11312654
TI  - Recent advances in arsenic carcinogenesis: modes of action, animal model systems,
      and methylated arsenic metabolites.
AB  - Recent advances in our knowledge of arsenic carcinogenesis include the
      development of rat or mouse models for all human organs in which inorganic
      arsenic is known to cause cancer-skin, lung, urinary bladder, liver, and kidney.
      Tumors can be produced from either promotion of carcinogenesis protocols (mouse
      skin and lungs, rat bladder, kidney, liver, and thyroid) or from complete
      carcinogenesis protocols (rat bladder and mouse lung). Experiments with p53(+/-)
      and K6/ODC transgenic mice administered dimethylarsinic acid or arsenite have
      shown some degree of carcinogenic, cocarcinogenic, or promotional activity in
      skin or bladder. At present, with the possible exception of skin, the arsenic
      carcinogenesis models in wild-type animals are more highly developed than in
      transgenic mice. Recent advances in arsenic metabolism have suggested that
      methylation of inorganic arsenic may be a toxification, rather than a
      detoxification, pathway and that trivalent methylated arsenic metabolites,
      particularly monomethylarsonous acid and dimethylarsinous acid, have a great deal
      of biological activity. Accumulating evidence indicates that these trivalent,
      methylated, and relatively less ionizable arsenic metabolites may be unusually
      capable of interacting with cellular targets such as proteins and even DNA. In
      risk assessment of environmental arsenic, it is important to know and to utilize
      both the mode of carcinogenic action and the shape of the dose-response curve at
      low environmental arsenic concentrations. Although much progress has been
      recently made in the area of arsenic's possible mode(s) of carcinogenic action, a
      scientific concensus has not yet been reached. In this review, nine different
      possible modes of action of arsenic carcinogenesis are presented and discussed
      induced chromosomal abnormalities, oxidative stress, altered DNA repair, altered
      DNA methylation patterns, altered growth factors, enhanced cell proliferation,
      promotion/progression, gene amplification, and suppression of p53.

PMID- 11312656
TI  - Vesicular release of ebola virus matrix protein VP40.
AB  - We have analysed the expression and cellular localisation of the matrix protein
      VP40 from Ebola virus. Full-length VP40 and an N-terminal truncated construct
      missing the first 31 residues [VP40(31-326)] both locate to the plasma membrane
      of 293T cells when expressed transiently, while a C-terminal truncation of
      residues 213 to 326 [VP40(31-212)] shows only expression in the cytoplasm, when
      analysed by indirect immunofluorescence and plasma membrane preparations. In
      addition, we find that full-length VP40 [VP40(1-326)] and VP40(31-326) are both
      released into the cell culture supernatant and float up in sucrose gradients. The
      efficiency of their release, however, is dependent on the presence of the N
      terminal 31 residues. VP40 that is released into the supernatant is resistant to
      trypsin digestion, a finding that is consistent with the formation of viruslike
      particles detected by electron microscopy. Together, these results provide strong
      evidence that Ebola virus VP40 is sufficient for virus assembly and budding from
      the plasma membrane.

PMID- 11312657
TI  - Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C adaptor.
AB  - Nef proteins of primate immunodeficiency viruses exert pleiotropic effects, such
      as enhanced endocytosis of CD4 and MHC-I cell surface molecules, perturbation of
      signal transduction cascades, and virion infectivity enhancement. Nef function
      intersects that of a number of cell kinases, including C kinases (PKCs) and Src
      family kinases. Here the interaction of HIV-1 Nef with Rack1 (receptor for
      activated C kinase 1) is reported. Nef binds the Rack1 C-terminal moiety in a
      yeast two-hybrid system and in cell-free pull-down assays and copurifies with in
      vitro translated Rack1. Nef and Rack1 partially colocalize on the trans-Golgi
      network and plasma membranes. The presence of Rack1 doubles Nef phosphorylation
      by PKCs in vitro. Our data agree with the idea that Rack1 acts as a Nef
      intracellular docking site, bringing Nef and PKCs together. Other signal
      transduction or endocytosis proteins, in particular Src-like kinases, might meet
      Nef by intermediation of the Rack1 adaptor.

PMID- 11312658
TI  - Human immunodeficiency virus type 1 clade A and D neurotropism: molecular
      evolution, recombination, and coreceptor use.
AB  - Human immunodeficiency virus type 1 (HIV-1) non-B clade viral infections of the
      brain have not been studied to date. Among nine AIDS patients from Nairobi,
      Kenya, infected with HIV-1 A (N = 5) or D (N = 4) clade strains, brain-derived
      HIV-1 env sequences displayed greater evolutionary distance than B clade brain
      derived viruses (P < 0.001). Similarly, molecular diversity between matched brain
      and spleen env clones was clade-dependent and concentrated in the hypervariable
      V4 region (P < 0.001), with phylogenetic clustering of sequences derived from the
      same organ. Brain-derived A and D clade sequences displayed significantly lower
      ratios of nonsynonymous/synonymous substitution rates (d(N)/d(S)) compared to
      matched spleen-derived clones and brain-derived B clade viruses. Interclade
      recombination events were infrequently observed among the present env sequences.
      A chimeric virus containing the C2V3 region from an A clade brain-derived
      sequence preferentially used CD4 and CCR5 for infection. These findings
      demonstrate that differences in molecular diversity in brain-derived sequences
      were dependent on the individual clade and domain within the env gene, but both B
      and non-B clade brain-derived viruses exhibit a preference for CCR5 as a
      coreceptor.

PMID- 11312659
TI  - Regression of canine oral papillomas is associated with infiltration of CD4+ and
      CD8+ lymphocytes.
AB  - Canine oral papillomavirus (COPV) infection is used in vaccine development
      against mucosal papillomaviruses. The predictable, spontaneous regression of the
      papillomas makes this an attractive system for analysis of cellular immunity.
      Immunohistochemical analysis of the timing and phenotype of immune cell
      infiltration revealed a marked influx of leukocytes during wart regression,
      including abundant CD4+ and CD8+ cells, with CD4+ cells being most numerous.
      Comparison of these findings, and those of immunohistochemistry using
      TCRalphabeta-, TCRgammadelta-, CD1a-, CD1c-, CD11a-, CD11b-, CD11c-, CD18-, CD21
      , and CD49d-specific monoclonal antibodies, with previously published work in the
      human, ox, and rabbit models revealed important differences between these
      systems. Unlike bovine papillomavirus lesions, those of COPV do not have a
      significant gamma/delta T-cell infiltrate. Furthermore, COPV lesions had numerous
      CD4+ cells, unlike cottontail rabbit papillomavirus lesions. The lymphocyte
      infiltrate in the dog resembled that in human papillomavirus lesions, indicating
      that COPV is an appropriate model for human papillomavirus immunity.

PMID- 11312660
TI  - Inhibition of Rb and p53 is insufficient for SV40 T-antigen transformation.
AB  - The SV40 large T-antigen (TAg) has proven useful in studying pathways involved
      with cell division and tissue homeostasis. TAg disrupts the normal action of
      tumor suppressors pRb and p53. It is unclear whether T-antigen inhibition of p53
      and pRb is sufficient for oncogenic transformation or if additional T-antigen
      activities are required. To pursue this question, cell lines were generated that
      coexpress an amino-terminal fragment of T-antigen (TAgN136), which has been shown
      to be sufficient to block pRb function, together with a dominant-negative p53.
      Neither focus formation nor saturation density was enhanced by coexpression of
      the dominant-negative p53 molecule, p53DD, along with TAgN136. Furthermore, a
      full-length TAg mutant incapable of binding p53 was capable of relieving contact
      inhibition, a hallmark of transformation. These results suggest the presence of a
      novel transforming activity in addition to the binding and inactivation of p53,
      requiring TAg amino acids 137 to 708.

PMID- 11312661
TI  - Capsid size determination in the P2-P4 bacteriophage system: suppression of sir
      mutations in P2's capsid gene N by supersid mutations in P4's external scaffold
      gene sid.
AB  - The sid gene of the P2-dependent phage P4 provides an external scaffold so P2 N
      gene encoded protomers assemble as T = 4 capsids rather than as P2's T = 7
      capsids. Mutations (sir) in the middle of N interfere with Sid's function. We
      describe a new P4 mutant class, nms ("supersid") mutations, which direct also P2
      sir to provide small capsids. Three different nms mutations were located near the
      sid end, commingled with sid(-) mutations. Suppression of sir by nms is not
      allele-specific. Our results favor this interpretation of capsid size control:
      (i) sir mutations reduce pN protomer flexibility and thereby interfere with the
      generation of T = 4 compatible hexons; (ii) the C-termini of Sid molecules link
      up when forming the scaffold; nms mutations strengthen these Sid-Sid contacts and
      thus allow the scaffold to force even sir-type protomers to form T = 4 compatible
      hexons. Some related findings concern suppression of N ts mutations by P4.

PMID- 11312662
TI  - Chimeric subgroup A respiratory syncytial virus with the glycoproteins
      substituted by those of subgroup B and RSV without the M2-2 gene are attenuated
      in African green monkeys.
AB  - Using the existing reverse genetics system developed for the subgroup A
      respiratory syncytial virus (RSV), a chimeric virus (designated rA-G(B)F(B)) that
      expresses subgroup B-specific antigens was constructed by replacing the G and F
      genes of the A2 strain with those of the 9320 strain of subgroup B RSV. rA
      G(B)F(B) grew well in tissue culture, but it was attenuated in the respiratory
      tracts of cotton rats and African green monkeys. To further attenuate this
      chimeric RSV, the M2-2 open reading frame was removed from rA-G(B)F(B). rA
      G(B)F(B)DeltaM2-2 was highly attenuated in replication in the respiratory tracts
      of the infected monkeys, but it provided complete protection against wild-type
      subgroup B RSV challenge following two doses of infection. In this study,
      rA2DeltaM2-2 (a recombinant A2 RSV that lacks the M2-2 gene) was also evaluated
      in African green monkeys. The replication of rA2DeltaM2-2 was highly restricted
      in both the upper and lower respiratory tracts of the infected monkeys and it
      induced titers of serum anti-RSV neutralizing antibody that were slightly lower
      than those induced by wild-type rA2. When rA2DeltaM2-2-infected monkeys were
      challenged with wild-type A2 virus, the replication of the challenge virus was
      reduced by approximately 100-fold in the upper respiratory tract and 45,000-fold
      in the lower respiratory tracts. rA2DeltaM2-2 and rA-G(B)F(B)DeltaM2-2 could
      represent a bivalent RSV vaccine composition for protection against multiple
      strains from the two RSV subgroups.

PMID- 11312663
TI  - ICAM-1 is required for resistance to herpes simplex virus type 1 but not
      interferon-alpha1 transgene efficacy.
AB  - The purpose of this study was to determine the role of ICAM-1 in ocular herpes
      simplex virus type 1 (HSV-1) infection. Wild-type and ICAM-1 knockout mice were
      assessed for resistance to ocular HSV-1 infection in the presence of naked DNA
      plasmid vector or plasmid DNA encoding interferon-alpha1 topically applied to the
      cornea of the mice. Wild-type mice showed greater resistance to HSV-1 infection
      compared to ICAM-1 knockout mice as measured by cumulative survival. The absence
      of ICAM-1 did not affect the efficacy of the interferon-alpha1 transgene against
      ocular HSV-1. Both ICAM-1 and wild-type mice treated with the transgene showed a
      reduction in viral load and antigen expression in the trigeminal ganglion
      compared to the plasmid vector-treated counterparts. In contrast, the presence of
      the transgene reduced the number of infiltrating cells into the cornea in
      comparison to plasmid vector DNA controls in the wild-type mice but not in the
      ICAM-1 knockout mice. Collectively, these results suggest that the IFN-alpha1
      transgene can restore resistance against HSV-1 infection in ICAM-1-deficient
      mice.

PMID- 11312664
TI  - Virion-associated HIV-1 Vpr: variable amount in virus particles derived from
      cells upon virus infection or proviral DNA transfection.
AB  - Human immunodeficiency virus type-1 (HIV-1) Vpr is a virion-associated protein
      implicated to have a role in AIDS pathogenesis. In regard to the amount of Vpr
      incorporated into virus particles, the published data vary widely. To address
      this, we quantitated Vpr in virus particles derived from diverse sources that are
      used to evaluate the biological effect of Vpr. Virus particles from infected
      cells showed only a small amount of Vpr. Interestingly, virus particles from
      cells cotransfected with HIV-1 proviral DNA lacking Vpr coding sequences
      (NLDeltaVpr) and a Vpr expression plasmid showed a drastic increase (29.4-fold)
      in the incorporation of Vpr. Furthermore, cotransfection involving NLDeltaVpr and
      different concentrations of Vpr expression plasmid resulted in virus particles
      containing Vpr in proportion to the Vpr expression plasmid used. The differences
      in virus particles with respect to Vpr as revealed by these studies should be
      taken into account in assessing the effect of Vpr.

PMID- 11312665
TI  - Inhibition of coxsackievirus B4 replication in stably transfected cells
      expressing human MxA protein.
AB  - Coxsackieviruses B (CVB) (B1-B6), positive-strand RNA viruses, cause a variety of
      diseases. CVB4 may have a causal role in insulin-dependent diabetes mellitus. IFN
      alpha inhibits CVB replication; however, the mechanism is not well known. The
      interferon-alpha-inducible human MxA protein exerts an antiviral activity against
      negative-strand RNA viruses and against Semliki Forest virus, a positive-strand
      RNA virus. To test the antiviral spectrum of MxA against CVB4, we took advantage
      of stably transfected Vero cells expressing MxA (Vero/MxA) in 98% of cells.
      Compared with control cells, in Vero/MxA cells, CVB4 yields were dramatically
      reduced and expression of the VP1 CVB protein analyzed by immunofluorescence was
      highly restricted. Furthermore, the accumulation of positive- and negative-strand
      CVB4 RNA was prevented as shown by in situ hybridization and RT-PCR. These
      results indicate that the antiviral activity of MxA extends to CVB4 and that its
      replication cycle is inhibited at an early step in Vero/MxA cells.

PMID- 11312666
TI  - Analysis of the complete DNA sequence of the temperate bacteriophage TP901-1:
      evolution, structure, and genome organization of lactococcal bacteriophages.
AB  - A complete analysis of the entire genome of the temperate lactococcal
      bacteriophage TP901-1 has been performed and the function of 21 of 56 TP901-1
      encoded ORFs has been assigned. This knowledge has been used to propose 10
      functional modules each responsible for specific functions during bacteriophage
      TP901-1 proliferation. Short regions of microhomology in intergenic regions
      present in several lactococcal bacteriophages and chromosomal fragments of
      Lactococcus lactis are suggested to be points of exchange of genetic material
      through homologous recombination. Our results indicate that TP901-1 may have
      evolved by homologous recombination between the host chromosome and a mother
      phage and support the observation that phage remnants as well as prophages
      located in the Lactococcus chromosome contribute significantly to bacteriophage
      evolution. Some proteins encoded in the early transcribed region of the TP901-1
      genome were more homologous to proteins encoded by phages infecting gram-positive
      hosts other than L. lactis. This protein homology argues for the occurrence of
      horizontal genetic exchange among these bacteriophages and indicates that they
      have access to a common gene pool.

PMID- 11312667
TI  - HBV X protein targets HIV Tat-binding protein 1.
AB  - The HBV X protein (HBx) is implicated in infection and development of
      hepatocellular carcinoma. HBx has a pleiotropic effect on cells, suggesting
      multiple targets in the virus-host cell interaction. We employed the cytoplasmic
      based two-hybrid screen and identified the HIV Tat-binding protein 1 (Tbp1) as a
      novel HBx interacting protein. Tbp1 interacts in vivo with HBx both in yeast and
      in animal cells. This interaction maps to the functionally important ATP-binding
      motif of Tbp1. Furthermore, HBx and Tbp1 interaction is functionally significant
      and regulates HBV transcription. Tbp1 homologues, such as Sug1, are known members
      of the proteasome 19S regulatory cap particle and have also been implicated in
      transcription coactivation. Remarkably, Tbp1 and Sug1 interact with multiple
      viral effector proteins including HIV Tat, SV40 large T antigen, and adenovirus
      E1A, establishing these proteins as important targets of the viral oncogenes.

PMID- 11312668
TI  - Role of the LTR region between the enhancer and promoter in mink cell focus
      forming murine leukemia virus pathogenesis.
AB  - Long terminal repeat (LTR) sequences are important determinants of mink cell
      focus-forming (MCF) murine leukemia virus pathogenesis. These sequences include
      the enhancer and sequences between the enhancer and promoter (DEN). In a previous
      study we showed that a virus missing the DEN region in its LTR was severely
      attenuated in its ability to induce thymic lymphoma. In this study we observed
      that a virus with an LTR consisting of DEN but no enhancer sequences was
      pathogenic. We compared the pathogenicity of this DEN virus with other LTR mutant
      MCF13 viruses that contained a single enhancer (1R) or a single enhancer plus DEN
      (1R + DEN). All LTR mutant viruses generated thymic lymphoma, however, at a much
      lower incidence and with a longer latency compared with wild-type (WT) MCF13
      virus. DEN virus replication in the thymus was the lowest compared with the 1R
      and 1R + DEN viruses. Viral replication in a different thymic subpopulation could
      not explain the decreased pathogenicity of the LTR mutant viruses compared with
      WT virus. However, lower levels of mutant virus replication in the thymus
      compared with WT during the preleukemic period may contribute to the attenuation
      of pathogenicity. The phenotype of tumors induced by the mutant viruses was
      similar and differed from tumors induced by WT virus by the presence of CD3(
      )CD4(-)CD8(-) cells. Analysis of LTR sequences of infectious virus rescued from
      tumors induced by the 1R and 1R + DEN viruses showed that amplification of
      enhancer sequences had occurred during tumor development. The lack of DEN virus
      expression by tumor cells led us to propose that DEN sequences may play a role at
      an early step in tumorigenesis.

PMID- 11312669
TI  - Autographa californica baculoviruses with large genomic deletions are rapidly
      generated in infected insect cells.
AB  - Defective interfering baculoviruses (DIs) lack considerable portions of the
      genome, interfere with the replication of helper virus, and cause the so-called
      "passage-effect" during serial passaging in insect cells and in bioreactor
      configurations. We investigated their origin by (nested) PCR and demonstrated
      that DIs lacking approximately 43% (d43) of their DNA are present in low-passage
      Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV)-E2 virus stocks
      and in polyhedra, but not in the authentic AcMNPV isolate obtained prior to
      passage in cell culture. To investigate whether DIs are rapidly generated de novo
      in Sf21 insect cells, a genetically homogeneous AcMNPV bacmid was serially
      passaged, resulting in the generation of d43 DIs within two passages. AT-rich
      sequences of up to 66 nucleotides of partly unknown origin were found at the
      deletion junctions in the d43 DI genomes. These data suggest that the rapid
      generation of DIs is an intrinsic property of baculovirus infection in insect
      cell culture and involves several recombination steps.

PMID- 11312670
TI  - Relationships between 80 human papillomavirus genotypes and different grades of
      cervical intraepithelial neoplasia: association and causality.
AB  - To clarify the causal relationship between human papillomavirus (HPV) and
      cervical intraepithelial neoplasia (CIN), we analyzed 386 unfixed biopsy
      specimens by blot hybridization at Tm -40 degrees C, targeting 38 skin and 42
      genital HPVs. By the recognition of PstI, BanI, and MspI cleavage patterns,
      single genital, but no skin's HPVs were identified with more than 10 copies per
      cell in 354 CIN (88 CIN I, 94 CIN II, and 172 CIN III). HPVs 40, 42, 43, 54, 62,
      or 71 was found in 10 CIN I, while HPVs 18, 30, 39, 51, 56, 59, 66, 68, 69, or 82
      was found in 35 CIN I, 20 CIN II, or 8 CIN III. On the other hand, HPVs 16, 31,
      33, 35, 52, 58, or 67 was identified in 43 CIN I, 74 CIN II, or 164 CIN III. The
      results are strongly indicative that most genital HPVs have potency to induce CIN
      I; however, HPV 16 and its closely related types are able to efficiently induce
      CIN III. We discuss the definition of causal HPV for CIN with regard to viral
      prevalence and viral load.

PMID- 11312671
TI  - Down-modulation of the costimulatory molecule, CD28, is a conserved activity of
      multiple SIV Nefs and is dependent on histidine 196 of Nef.
AB  - In this study Nef proteins derived from simian immunodeficiency virus (SIV) and
      human immunodeficiency virus (HIV) were compared to assess their abilities to
      down-modulate the cell surface levels of the T-cell costimulatory molecule CD28.
      We demonstrate that in addition to Nef derived from the prototypic SIVmac239, Nef
      proteins encoded by the pathogenic SIVsmmPBj molecular clone and the SIVsmmB670
      isolate also down-modulate cell surface CD28. In contrast, Nef proteins derived
      from HIV failed to down-modulate CD28. We have also identified H196 as a critical
      residue which influences the capacity of SIVmac Nef to down-modulate CD28. Nef
      derived from SIVmacJ5 failed to down-modulate cell surface CD28, whereas a Q196H
      substitution mutant of SIVmacJ5 Nef was able to down-modulate cell surface CD28.
      Conversely, substitution of H196 to Q196 in SIVmac239 Nef resulted in a mutant
      that had minimal effect on cell surface CD28 expression, despite retaining the
      capacity to down-modulate cell surface CD3epsilon. H196 lies immediately adjacent
      to a documented di-leucine endocytic motif and mutation of this motif also
      abrogated the ability of SIVmac239 Nef to down-modulate CD28. These findings
      demonstrate that down-modulation of the costimulatory molecule, CD28, and
      clonotypic TCR/CD3 complex are conserved attributes of SIV Nef.

PMID- 11312672
TI  - A new strategy for site-specific protein modification: analysis of a Tat peptide
      TAR RNA interaction.
AB  - Site-specific modification of proteins and peptides with reporter molecules
      provides a powerful research tool in chemistry and biology. We report the
      synthesis and application of a tyrosine analogue, N-alpha-Fmoc-3-acetyl-L
      tyrosine, for selective modification of proteins. As a model system, we
      synthesized the human immunodeficiency virus type 1 (HIV-1) Tat peptide (amino
      acids 47-56) containing the arginine rich RNA-binding region and replaced the Tyr
      47 with 3-acetyl-tyrosine. The acetyl-Tyr-Tat peptide was subsequently labeled
      with a fluorescein derivative to study RNA-protein interactions by fluorescence
      energy transfer experiments. Our results showed that the Tat peptide binds to the
      rhodamine labeled TAR RNA with a dissociation constant (KD) of 1.0 +/- 0.5 nM.
      This strategy of selective protein modification offers a versatile new procedure
      for labeling peptides of biological interest at a desired site when several
      nucleophilic side chains of lysine and cysteine are present. These methods would
      provide tools for postsynthetic peptide modification and introducing biophysical
      probes for structural and functional analysis of proteins.

PMID- 11312673
TI  - A chemoselective method for site-specific immobilization of peptides via aminooxy
      group.
AB  - Site-specific modification of peptides and proteins is an important area of basic
      research for preparation of well-defined biosensors and probes. The unique
      properties of aminooxy group present an opportunity for chemoselective site
      specific immobilization of peptides to prepare well-defined biosensors. We have
      prepared FLAG peptide derivatives containing L-epsilon-aminooxylysine (L-epsilon
      AOLys, 1a) and L-lysine units in their sequence at the C- and N-terminals via
      solid-phase synthesis. Site-specific modification of peptides through aminooxy
      group was demonstrated in the preparation of biosensors and selective conjugation
      in the preparation of biotinylated probes. Effect of the incorporation of L
      epsilon-AOLys (1a) into the peptide sequence and its subsequent labeling on the
      FLAG epitopic character was measured using a surface plasmon resonance detector.
      It was found that incorporation of L-epsilon-AOLys (1a) into the FLAG peptide and
      site-specific immobilization through aminooxy group preserved the integrity of
      FLAG epitope.

PMID- 11312674
TI  - Polymeric prodrug for release of an antitumoral agent by specific enzymes.
AB  - The clinical usefulness of antitumor chemotherapy has been strongly limited by
      the lack of specificity of most anticancer drugs, which act also against healthy
      cells. The aim of this work was to design, synthesize, and evaluate a
      macromolecular prodrug of Cytarabine, a known antitumor drug, which is a specific
      substrate for plasmin enzyme whose concentration is high in various kinds of
      tumor mass as a result of plasminogen activator secretion. alpha,beta-Poly(N
      hydroxyethyl)-DL-aspartamide (PHEA), a known synthetic and biocompatible
      polyamino acid, was used as a drug carrier, and Cytarabine was linked to PHEA by
      D-Val-Leu-Lys spacer synthesized beginning from Cbz-D-Val-LeuOH dipeptide and N6
      CbzLys methyl ester. The content of Cytarabine in the purified PHEA-D-Val-Leu-Lys
      Cytarabine conjugate was equal to 3% w/w. In vitro experiments in the presence of
      plasmin evidenced the ability of this enzyme to strongly increase drug release
      from the macromolecular prodrug, as well as plasma incubation shows high
      stability of drug-polymer linkage. The direct linkage of Cytarabine to PHEA was
      also performed and, like PHEA-D-Val-Leu-Lys-Cytarabine conjugate, the obtained
      PHEA-Cytarabine conjugate showed high stability in plasma, but no release of
      Cytarabine was revealed in the presence of plasmin.

PMID- 11312675
TI  - Biotinylated indoles as probes for indole-binding proteins.
AB  - Biotinylated indoles were prepared for application as bifunctional probes for the
      detection of indole-binding proteins which participate in the life processes of
      humans, animals, plants, and bacteria. The indole nucleus was functionalized, at
      ring positions 3, 5, or 6, by attachment of a 2-aminoethyl group, which was then
      coupled to the carboxyl moiety of biotin, via a spacer composed of 3 or 4
      concatenated beta-alanine residues. The constructs thus obtained were able to
      inhibit tryptophanase activity, similarly to indole in a concentration-dependent
      manner. They also bound strongly to lysozyme and weakly to bovine and human serum
      albumins, in accordance with the known affinities of these proteins for indole
      and 3-(2-aminoethyl)indole (tryptamine). The biotin end of the protein-bound
      bifunctional probes could then be detected by coupling to (strept)avidin
      conjugated to alkaline phosphatase or horseradish peroxidase, followed by
      incubation with substrates which are converted by these enzymes to intensely
      colored or chemiluminescent products.

PMID- 11312676
TI  - Drug delivery systems employing 1,6-elimination: releasable poly(ethylene glycol)
      conjugates of proteins.
AB  - Using lysozyme as a representative protein substrate that loses its activity when
      PEGylation takes place on the epsilon-amino group of lysine residues, various
      amounts of a novel releasable PEG linker (rPEG) were conjugated to the protein.
      rPEG-lysozyme conjugates were relatively stable in pH 7.4 buffer for over 24 h.
      However, regeneration of native protein from the rPEG conjugates occurred in a
      predictable manner during incubation in high pH buffer or rat plasma, as
      demonstrated by enzymatic activity and structural characterization. The rates of
      regeneration were also correlated with PEG number: native lysozyme was released
      more rapidly from the monosubstituted conjugate than from the disubstituted
      conjugate, suggesting possible steric hindrance to the approach of cleaving
      enzymes. Recovery of normal activity and structure for the regenerated native
      lysozyme was shown by a variety of assays.

PMID- 11312677
TI  - Synthesis, characterization, and relaxivity of two linear Gd(DTPA)-polymer
      conjugates.
AB  - Two linear polyamide conjugates of Gd(DTPA)2- were synthesized and characterized
      by high-resolution nuclear magnetic resonance (NMR) spectroscopy and size
      exclusion chromatography (SEC). DTPA was copolymerized with two different
      diamines, 1,6-hexanediamine and trans-1,4-cyclohexanediamine, yielding the
      polymers DTPA-HMD and DTPA-CHD, with low polydispersity. Their molecular
      flexibility in solution was studied using 13C spin-lattice relaxation time
      measurements, indicating that the cyclohexanediamine linking moiety of the DTPA
      HMD polymer is more rigid than that of DTPA-CHD. The influence of the flexibility
      of the linking functionalities on the relaxivity of the Gd3+-DTPA-polymer
      conjugates was studied by water nuclear magnetic relaxation dispersion (NMRD).
      The relaxivity of the Gd(DTPA-CHD) polymer was only slightly higher than that of
      the Gd(DTPA-HMD) polymer, and only two times higher than the usual values for
      small Gd-DTPA-like chelates. The low relaxivities obtained for both polymers,
      much lower than expected from the polymer apparent molecular weights, result from
      their substantial residual flexibility, and also from a too long, nonoptimal,
      value of the inner-sphere water exchange rate. These polymeric compounds are also
      cleared very quickly from the blood of rats, indicating that they are of limited
      value as blood pool contrast agents for MRA.

PMID- 11312678
TI  - Renal metabolism of 3'-iodohippuryl N(epsilon)-maleoyl-L-lysine (HML)-conjugated
      Fab fragments.
AB  - Renal localization of radiolabeled antibody fragments constitutes a problem in
      targeted imaging and radiotherapy. Recently, we reported use of a novel
      radioiodination reagent, 3'-[131I]iodohippuryl N(epsilon)-maleoyl-L-lysine (HML),
      that liberates m-iodohippuric acid before antibody fragments are incorporated
      into renal cells. In mice, HML-conjugated Fab demonstrated low renal
      radioactivity levels from early postinjection times. In this study, renal
      metabolism of HML-conjugated Fab fragments prepared by different thiolation
      chemistries and by direct radioiodination were investigated to determine the
      mechanisms responsible for the low renal radioactivity levels. Fab fragments were
      thiolated by 2-iminothiolane modification or by reduction of disulfide bonds in
      the Fab fragments, followed by conjugation with radioiodinated HML to prepare
      [131I]HML-IT-Fab and [125I]HML-Fab, respectively. In biodistribution studies in
      mice, both [131I]HML-IT-Fab and [125I]HML-Fab demonstrated significantly lower
      renal radioactivity levels than those of [125I]Fab. In subcellular distribution
      studies, [125I]Fab showed migration of radioactivity from the membrane to the
      lysosomal fraction of the renal cells from 10 to 30 min postinjection. On the
      other hand, the majority of the radioactivity was detected only in the membrane
      fraction at the same time points after injection of both [131I]HML-IT-Fab and
      [125I]HML-Fab. In metabolic studies, while [125I]Fab remained intact at 10 min
      postinjection, both HML-conjugated Fab fragments generated m-iodohippuric acid as
      a radiometabolite at the same postinjection time. [131I]HML-IT-Fab registered two
      radiometabolites (intact [131I]HML-IT-Fab and m-iodohippuric acid), whereas
      additional radiometabolites were observed with [125I]HML-Fab. This suggested that
      metabolism of both HML-conjugated Fab fragments would occur in the membrane
      fractions of the renal cells. The findings of this study reinforced our previous
      hypothesis that radiochemical design of antibody fragments that liberate
      radiometabolites that are excreted into the urine by the action of brush border
      enzymes would constitute a useful strategy to reduce renal radioactivity levels
      from early postinjection times.

PMID- 11312679
TI  - Chemistry of sulforhodamine--amine conjugates.
AB  - Commercially-available sulforhodamine sulfonyl chlorides contain two isomeric
      monosulfonyl chlorides. Conjugates of these isomers with amines have different
      properties because the sulfonamide formed from one isomer can undergo ring
      closure to a colorless sultam. This chemistry has been examined for a model
      conjugate with methylamine and for a bioconjugate with 2'(3')-O-[N-(2
      aminoethyl)carbamoyl]ATP. The interaction of each isomer of the latter conjugates
      with myosin subfragment 1 has been characterized. Significant differences between
      the two isomers are observed in these interactions.

PMID- 11312680
TI  - Rational design of a potent, long-lasting form of interferon: a 40 kDa branched
      polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis
      C.
AB  - A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40
      kilodalton branched poly(ethylene glycol) was designed, synthesized, and
      characterized. Mono-pegylated interferon alpha-2a was comprised of four major
      positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The
      in vitro anti-viral activity of pegylated interferon alpha-2a was found to be
      only 7% of the original activity. In contrast, the in vivo antitumor activity was
      severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha
      2a showed no immunogenicity in mice. After subcutaneous injection of pegylated
      interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase
      in mean plasma residence time concomitant with sustained serum concentrations
      were observed relative to interferon alpha-2a. These preclinical results suggest
      a significantly enhanced human pharmacological profile for pegylated interferon
      alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed
      the superior efficacy of pegylated interferon alpha-2a compared to unmodified
      interferon alpha-2a.

PMID- 11312681
TI  - 4-oxo-4H-quinolizine-3-carboxylic acids as Mg2+ selective, fluorescent
      indicators.
AB  - In this paper, we present the synthesis of a new series of substituted 4-oxo-4H
      quinolizine-3-carboxylic acids and the evaluation of their fluorescent response
      upon complexation with Mg2+ and Ca2+. This has led to the development of the
      first Mg2+-selective, ratioable fluorescent indicators. We found that 4-oxo-4H
      quinolizine-3-carboxylates are excellent fluorophores which show a strong
      fluorescent response to Mg2+ but not to Ca2; the latter metal ion often causing
      interference during Mg2+ measurements with previously described indicators. The
      dissociation constants of the studied fluorophores-around 1.0 mM-are of the same
      order of magnitude as is usually observed for intracellular Mg2+.

PMID- 11312682
TI  - Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging.
AB  - Angiogenesis is a critical step in tumor development and more than 25
      angiogenesis inhibitors are currently in clinical trials. Noninvasive in vivo
      imaging of angiogenesis represents a unique opportunity of repeatedly
      quantitating microvascular parameters prior to and during anti-angiogenic
      treatments. While several imaging tracers have been proposed for MR and nuclear
      imaging, there does not exist any consensus of what constitutes an ideal size of
      an imaging agent. A series of synthetic pegylated DOTA derivatized graft
      copolymers (30, 60, 120 kDa) were synthesized and their in vivo behavior tested
      in two breast cancer models differing in vascular endothelial growth factor
      (VEGF) expression. Polymers were labeled with different lanthanides (Eu, Gd, Dy)
      and absolute blood and tumor concentrations were determined by ICP-AES
      measurements. DOTA and the 30 kDa polymers underwent renal clearance resulting in
      low plasma levels. Slow leakage across neovasculature into tumor interstitium was
      clearly dependent on the molecular mass of all tested agents in MCF-7 tumors.
      However, a cutoff was observed with minimal extravasation occurring at and above
      120 kDa in well differentiated MCF-7 tumors. VEGF overexpression caused
      detectable differences in extravasation of all polymers, including the 120 kDa
      compound. We conclude that large molecular weight contrast agents with a
      molecular mass of <120 kDa extravasate from experimental tumor neovasculature and
      may not be an accurate marker for measuring true blood volume fractions when in
      vivo imaging is performed in the steady state.

PMID- 11312683
TI  - Tumor targeting of radiometal labeled anti-CEA recombinant T84.66 diabody and
      t84.66 minibody: comparison to radioiodinated fragments.
AB  - Recombinant antibody fragments offer potential advantages over intact monoclonal
      antibodies in the radioimmunoscintigraphy (RIS) of solid tumors. Due to their
      smaller molecular size, antibody fragments have shown rapid tumor targeting and
      blood clearance, a more uniform tumor distribution and a lower potential to
      elicit a human immune response. Previously, we have expressed two genetically
      engineered antibody fragments, the T84.66 diabody (scFv dimer) and the T84.66
      minibody (scFv-CH3 dimer), specific to carcinoembryonic antigen (CEA). When
      radioiodinated, both antibody fragments exhibited rapid tumor targeting and rapid
      blood clearance in xenografted mice. To extend and optimize their future clinical
      RIS utility with radiometals, these antibody fragments were conjugated with the
      macrocycle 1,4,7,10-tetraazacyclododecane N,N',N' ',N' "-tetraacetic acid (DOTA)
      and labeled with 111In. Tumor targeting and biodistribution studies were carried
      out in athymic mice xenografted with a human colorectal tumor cell line, LS174T.
      The [111In]T84.66 diabody (55 kDa) exhibited very rapid tumor targeting with 12.5
      +/- 0.4% injected dose per gram (% ID g(-1) +/- standard error) at 2 h and
      reached a maximum of 13.3 +/- 0.9% ID g(-1) at 6 h. However, kidney uptake was
      observed to reached a peak of 183.5 +/- 21.0% ID g(-1) at 6 h, a result similar
      to that reported by others for other low molecular weight fragments labeled with
      radiometals. Preadministration of an oral dose of D-lysine resulted in a 59%
      lowering of the renal accumulation at 6 h, but was accompanied by a 31% reduction
      of tumor uptake to 9.2 +/- 1.2% ID g(-1). The second recombinant antibody
      fragment, the [111In]T84.66 minibody (80 kDa), displayed rapid tumor targeting of
      14.2 +/- 6.1% ID g(-1) at 2 h, and reached a maximum activity of 24.5 +/- 6.1% ID
      g(-1) by 12 h. Renal uptake achieved a plateau of 12-13% ID g(-1) which cleared
      to 7.2% ID g(-1) at 72 h. However, hepatic uptake was elevated and reached a
      maximum of 26.0 +/- 1.0% ID g(-1) at 12 h in these xenograft-bearing mice.
      Experiments in nontumor bearing mice showed a reduction of hepatic activity at 12
      h to 16.6 +/- 1.5% ID g(-1), indicative of an intrinsic hepatic accumulation of
      the [111In]DOTA-T84.66 minibody or metabolites. While the anti-CEA [111In]DOTA
      T84.66 diabody and T84.66 minibody retain the rapid tumor targeting properties of
      the radioiodinated form, the normal organ accumulation (kidneys and liver,
      respectively) of the [111In]DOTA forms appeared problematic for RIS and RIT
      applications. Development of alternative blocking strategies or new metabolizable
      chelates are under investigation to enhance the utility of the radiometal form of
      these and other promising recombinant antibody fragments.

PMID- 11312684
TI  - Phenylboronic acid-salicylhydroxamic acid bioconjugates. 1. A novel boronic acid
      complex for protein immobilization.
AB  - A chemical affinity system exhibiting antibody-like properties is described. The
      system exploits bioconjugates with appended phenylboronic acid (PBA) moieties and
      a support-bound phenylboronic acid complexing reagent derived from
      salicylhydroxamic acid (SHA) for protein immobilization on a chromatographic
      support. The structure of the PBA.SHA complex was characterized by 11B NMR and
      mass spectrometry and compared with complexes derived from model compounds.
      Protein modification reagents were synthesized from 3-aminophenylboronic acid and
      utilized to prepare bioconjugates from alkaline phosphatase (AP) and horseradish
      peroxidase (HRP). AP obtained from one source afforded PBA bioconjugates
      exhibiting significant loss of enzymatic activity, whereas AP obtained from a
      second source afforded PBA bioconjugates exhibiting only a modest loss of
      enzymatic activity. Conversely, HRP afforded PBA bioconjugates exhibiting no loss
      of enzymatic activity. SHA-modified Sepharose was prepared by reaction of methyl
      4-[(6-aminohexanoylamino)methyl]salicylate with CNBr-activated Sepharose 4B,
      followed by treatment with aqueous alkaline hydroxylamine. PBA-AP and PBA-HRP
      conjugates were efficiently immobilized on SHA-Sepharose at pH 8.3. PBA-AP
      conjugates were retained after washing with acidic buffers at pH 6.7, 4.2, and
      2.5, whereas PBA-HRP conjugates were retained after washing with buffer at pH
      6.7, but were eluted to some extent at and below pH 4.2. The results are
      interpreted in terms of multivalent interactions involving boronic acid complex
      formation between the enzyme bioconjugates and immobilized complexing reagent.

PMID- 11312685
TI  - Phenylboronic acid-salicylhydroxamic acid bioconjugates. 2. Polyvalent
      immobilization of protein ligands for affinity chromatography.
AB  - Phenylboronic acid bioconjugates prepared from alkaline phosphatase by reaction
      with either 2,5-dioxopyrrolidinyl 3-[N-[3-(1,3,2-dioxaboran-2
      yl)phenyl]carbamoyl]propanoate (PBA-XX-NHS) or 2,5-dioxopyrrolidinyl 6-[[3,5-di
      (1,3,2-dioxaboran-2-yl)phenyl]carbonylamino]hexanoate (PDBA-X-NHS) were compared
      with respect to the efficiency with which they were immobilized on
      salicylhydroxamic acid-modified Sepharose (SHA-X-Sepharose) by boronic acid
      complex formation. When immobilized on moderate capacity SHA-X-Sepharose (5.4
      micromol of SHA/mL of gel), PDBA-alkaline phosphatase conjugates were shown to be
      stable with respect to both the alkaline (pH 11.0) and acidic (pH 2.5) buffers
      utilized to recover anti-alkaline phosphatase during affinity chromatography.
      Boronic acid complex formation was compared to covalent immobilization of
      alkaline phosphatase on Affi-Gel 10 and Affi-Gel 15. PDBA-AP.SHA-X-Sepharose was
      shown to afford superior performance to both Affi-Gel 10 and Affi-Gel 15 with
      respect to immobilization of alkaline phosphatase, retention of anti-alkaline
      phosphatase and recovery of anti-alkaline phosphatase under alkaline conditions.
      High capacity SHA-X-Sepharose (> or = 7 micromol of SHA/mL of gel) was shown to
      afford superior performance to moderate capacity SHA-X-Sepharose (4.5 micromol of
      SHA/mL of gel) with respect to stability at pH 11.0 and pH 2.5 when a PDBA
      alphaHuman IgG conjugate with a low incorporation ratio of only 1.5:1 was
      immobilized on SHA-X-Sepharose and subsequently utilized for affinity
      chromatography of Human IgG. The results are interpreted in terms of either a
      bivalent or trivalent interaction involving boronic acid complex formation.

PMID- 11312686
TI  - Cationic lipid polymerization as a novel approach for constructing new DNA
      delivery agents.
AB  - In vivo gene delivery mediated by cationic lipids is often compromised by
      aggregation due to complexation with proteins in the blood. To improve the
      stability of cationic lipid-DNA complexes, the present study aimed to develop a
      novel approach in which a poly(cationic lipid) (PCL) is utilized to form stable
      cationic polyplexes for gene transfection. Hydrogenation of the acrylamide
      analogue of betaAE-DMRI, the polymerizable precursor of PCL, provided a monomeric
      lipid derivative (MHL) which was used for direct comparison of corresponding
      lipoplex stability, toxicity, and transfection activity. Various formulations of
      cationic liposomes, such as MHL, MHL-cholesterol (Chol), PCL, PCL-Chol, DOTAP
      Chol, and commercially available lipofectamine were generated and examined in
      this study. The new poly(cationic lipid) did not display any significant toxicity
      to rat hepatocytes or Hep G2 cells as indicated by an LDH leakage assay.
      Furthermore, PCL was significantly less toxic than MHL, DOTAP-Chol or
      lipofectamine. Suspensions of PCL were resistant to aggregation even after 24 h
      of exposure to solutions containing 50 and 100% fetal bovine serum (FBS). In
      contrast, suspensions of lipofectamine extensively aggregated after 24 h of
      exposure to 50% FBS. To examine the influence of lipid polymerization on gene
      transfer activity, liposome-mediated transfections of a luciferase vector (pGL3)
      were performed in Hep G2 and Alexander cell lines. The luciferase activity of the
      PCL formulations in Hep G2 cells were similar to those of the MHL, DOTAP-Chol and
      lipofectamine formulations, demonstrating that lipid polymerization does not
      compromise transfection activity. In comparison to the monomeric precursor MHL
      and to the industry transfection standards DOTAP and lipofectamine, the novel
      poly(cationic lipid) exhibited the lowest cytotoxicity, was the most resistant to
      serum-induced aggregation and had comparable transfection activity when
      coformulated with cholesterol. This novel polymerization approach for the
      development of stable and active polyplexes may prove a valuable alternative for
      in vivo gene delivery.

PMID- 11312687
TI  - Diquaternary ammonium compounds as transfection agents.
AB  - Diquaternary ammonium salts constitute a new class of reagent for mediating
      transfection of DNA in mammalian cell lines. N,N'-dioleyl-N,N,N',N'-tetramethyl
      1,2-ethanediamine (TmedEce), N,N'-dioleyl-N,N,N',N'-tetramethyl-1,3
      propanediamine (PropEce), N,N'-dioleyl-N,N,N',N'-tetramethyl-1,6-hexanediamine
      (HexEce), and their corresponding N,N'-dicetyl saturated analogues (TmedAce,
      PropAce and HexAce) have all been synthesized and characterized. They were
      prepared via a bis-Menshutkin reaction of the corresponding tetramethyldiamine
      with 2.2 M equiv of a long-chain alkyl halide (saturated or unsaturated). The
      reaction was run in anhydrous acetonitrile for ca. 3 days at 60 degrees C, which
      produced the diquaternary ammonium halides in good to nearly quantitative yields
      for most derivatives. DNA transfection comparable to commercially available
      reagents such as Lipofectin, Lipofectace, Lipofectamine, and O
      ethyldioleoylphosphatidylcholinium triflate has been achieved in vitro with these
      new reagents. There was no need to use a colipid for effective transfection, but
      serum did significantly inhibit transfection. The saturated and the unsaturated
      derivatives differed with respect to hydration behavior. The saturated
      derivatives appeared to retain a lamellar-type crystalline array structure upon
      hydration, whereas the unsaturated versions formed micelles and/or liposomes,
      depending on the ionic strength: HexEce was micellar in both water and saline;
      PropEce was micellar in water but lamellar in saline; and TmedEce was lamellar in
      both. Despite these different hydration patterns, all of these unsaturated
      derivatives formed productive transfection complexes with DNA. Varying the
      distance between the quaternary sites affected transfection efficacy in the order
      HexAce > TmedAce = PropAce for the saturated derivatives and in the order PropEce
      = HexEce > TmedEce, with a smaller spread, for the unsaturated derivatives.

PMID- 11312688
TI  - Metabolism and renal clearance of 111In-labeled DOTA-conjugated antibody
      fragments.
AB  - Radiometal-labeled antibody fragments are promising reagents for
      radioimmunotherapy due to their high tumor uptake and rapid pharmacokinetics, but
      their therapeutic potentials are limited by high uptake and retention in the
      kidney. Identification of metabolic products is a first step in designing
      rationale approaches to lower kidney uptake. Previous studies in rats have shown
      that 111In-labeled DTPA-conjugated antibody fragments (via lysine residues) were
      degraded to an DTPA-epsilon-amino-lysine derivative and retained in the lysosomal
      compartments of the liver and kidney [Rogers et al. (1995) Cancer Res. 55, 5714s
      5720s]. To determine the metabolic profile of another widely used metal-chelate,
      [111In]DOTA conjugated to lysines in antibody fragments via active ester
      chemistry, we analyzed kidney homogenates from nude mice injected with an
      [111In]DOTA-Fab generated enzymatically from the anti-lymphoma intact antibody
      Rituxan. The major kidney metabolite was identified as [111In]DOTA-epsilon-amino
      lysine by comparison to an authentic synthetic standard. This end product was
      also identified in the urine, along with relatively small amounts of [111In]DOTA
      Fab. Since injection of [111In]DOTA-epsilon-amino-lysine into nude mice resulted
      in rapid clearance into the urine without kidney retention, it is likely that the
      renal retention observed was due to kidney uptake of [111In]DOTA-Fab, followed by
      lysosomal degradation to [111In]DOTA-epsilon-amino-lysine, which is only slowly
      cleared from this compartment. This observation is supported by autoradiographs
      of the kidney showing rapid localization of radioactivity into the distal regions
      of the kidney cortex. To extend this analysis to clinical trials, we have also
      analyzed urine taken from a patient injected with the intact antibody [111In]DOTA
      cT84.66. In that example, we found that the major radioactive species was also
      [111In]DOTA-epsilon-amino-lysine.

PMID- 11312689
TI  - Carbohydrate-directed conjugation of cobra venom factor to antibody by selective
      derivatization of the terminal galactose residues.
AB  - Cobra venom factor (CVF) can cause cell death by complement-mediated bystander
      cell lysis. Several studies have investigated CVF for application in cancer
      therapy by conjugating CVF to antibodies against tumor cell surface-specific
      antigens via the side-chain amino acid residues. In most cases, the activity of
      CVF was markedly impaired, presumably by modification of the factor B binding
      domain due to random derivatization. Since CVF is a glycoprotein and its
      oligosaccharide chains are distal to the factor B binding domain, coupling of CVF
      to antibodies through its oligosaccharide chains is expected to yield
      immunoconjugates with retention of CVF activity and elimination of the
      immunoreactivity of the terminal alpha-galactosyl residues. In this study, we
      investigated the carbohydrate site-directed conjugation of CVF to a monoclonal
      IgG specific to a cell-surface antigen of human ovarian cancer cells. The
      terminal galactosyl residues of CVF were selectively modified at C-6 by treatment
      with galactose oxidase, and the generated aldehyde groups were derivatized in
      situ with hydrazides containing either protected thiol or maleimide functional
      groups. The CVF derivatives were allowed to react with thiol groups introduced to
      the antibody by derivatization with 2-iminothiolane to yield carbohydrate site
      directed CVF-antibody conjugates. In both cases, 30-40% of the antibody cross
      linked to CVF to yield predominantly monovalent CVF-antibody conjugates. The
      purified immunoconjugates retained 70-75% of CVF activity and significant level
      of antigen-binding capacity. This is the first study to exploit the
      oligosaccharide chains of CVF for the preparation of active immunoconjugates.

PMID- 11312690
TI  - Effects of structure of beta-cyclodextrin-containing polymers on gene delivery.
AB  - Linear cationic beta-cyclodextrin-based polymers (betaCDPs) are capable of
      forming polyplexes with nucleic acids and transfecting cultured cells. The
      betaCDPs are synthesized by the condensation of a diamino-cyclodextrin monomer A
      with a diimidate comonomer B. In this paper, the effects of polymer structure on
      polyplex formation, in vitro transfection efficiency and toxicity are elucidated.
      By comparison of the betaCDPs to polyamidines lacking cyclodextrins, the
      inclusion of a cyclodextrin moiety in the comonomer A units reduces the IC50s of
      the polymer by up to 3 orders of magnitude. The spacing between the cationic
      amidine groups is also important. Different polymers with 4, 5, 6, 7, 8, and 10
      methylene units (betaCDP4, 5, 6, 7, 8, and 10) in the comonomer B molecule are
      synthesized. Transfection efficiency is dependent on comonomer B length with up
      to 20-fold difference between polymers. Optimum transfection is achieved with the
      betaCDP6 polymer. In vitro toxicity varied by 1 order of magnitude and the lowest
      toxicity is observed with betaCDP8. The LD40 of the betaCDP6 to mice is 200
      mg/kg, making this polymer a promising agent for in vivo gene delivery
      applications.

PMID- 11312691
TI  - Steric stabilization of fusogenic liposomes by a low-pH sensitive PEG--diortho
      ester--lipid conjugate.
AB  - We describe the synthesis and characterization of a pH-sensitive poly(ethylene
      glycol)-diortho ester-distearoyl glycerol conjugate (POD). POD was prepared by a
      one-step synthesis, and its acid sensitivity characterized by TLC. The conjugate
      was found to be stable at neutral pH for greater than 3 h but degraded completely
      within 1 h at pH 5. Liposomes composed of 10% of POD and 90% of a fusogenic
      lipid, dioleoyl phosphatidylethanolamine (DOPE) were readily prepared and
      remained stable for up to 12 h in neutral buffer as shown by photon correlation
      spectrometry and a liposome contents leakage assay. However, when POD/DOPE
      liposomes were incubated in acidic pH as mild as 5.5, they aggregated and
      released most of their contents within 30 min. The kinetics of content release
      from POD/DOPE liposomes consisted of two phases, a lag phase, and a burst phase.
      The lag phase is inversely correlated with pH and the logarithm of the length of
      lag phase showed a linear relationship with the buffer pH. When the POD/DOPE
      liposomes were incubated in 75% of fetal bovine serum at 37 degrees C, they
      remained as stable as traditional PEG-grafted liposomes for 12 h but released 84%
      of the encapsulated ANTS in the following 4 h. Upon intravenous administration
      into mice, liposomes composed of 10% POD and 90% DOPE were cleared from
      circulation by a one-compartment kinetics with a half-life of about 200 min. POD
      is an example for the design of a novel category of pH sensitive lipids composed
      of a headgroup, an acid-labile diortho ester linker and a hydrophobic tail. The
      uniquely fast degradation kinetics of POD at pH 5-6 and its ability to stabilize
      liposomes in serum make the conjugate suitable for applications for triggered
      drug release systems targeted to mildly acidic bio-environments such as
      endosomes, solid tumors, and inflammatory tissues.

PMID- 11312692
TI  - Enzyme conjugation to the polysaccharide chitosan: smart biocatalysts and
      biocatalytic hydrogels.
AB  - Laccase from Coriolopsis gallica was conjugated to the renewable biopolymer
      chitosan using carbodiimide chemistry. The laccase-chitosan conjugate was
      observed to offer three unique properties. First, the laccase-chitosan conjugate
      displayed pH-responsive behavior such that the conjugate was soluble and active
      under acidic conditions, but precipitated when the pH was raised toward
      neutrality. Second, the laccase-chitosan conjugate was more stable than free
      laccase at extreme pHs. At pH 1, the inactivation rate constant (k(in)) for the
      soluble laccase-chitosan conjugate was 20-fold less than that for free laccase.
      At pH 13, k(in) for the insoluble laccase-chitosan conjugate was nearly 3-fold
      less than that for free laccase. Finally, the laccase-chitosan conjugate could be
      cross-linked under mild conditions to create biocatalytic hydrogels. Potential
      benefits for enzyme-chitosan conjugates are discussed.

PMID- 11312693
TI  - Synthesis of fluorogenic substrates for continuous assay of phosphatidylinositol
      specific phospholipase C.
AB  - An improved synthesis of fluorogenic substrate analogues for phosphatidylinositol
      specific phospholipase C (PI-PLC) is described. The water-soluble substrates,
      which are derived from fluorescein, are not fluorescent until cleaved by the
      enzyme, and provide a convenient means to continuously monitor PI-PLC activity.
      The improvement in the synthesis lies in the method used to protect the hydroxyl
      groups of the inositol portion of the substrate molecule and allows a milder
      deprotection procedure to be used. The result is a much more reproducible
      synthesis of the substrate. The improved procedure has been employed to
      synthesize a series of fluorogenic substrates, which differ in the length of the
      aliphatic tail attached to the fluorescein portion of the molecule. The length of
      the tail was found to have a significant effect on the rate of cleavage of these
      substrates.

PMID- 11312694
TI  - Mechanistic investigation of smart polymer-protein conjugates.
AB  - Many affinity separation and diagnostic applications rely upon both capture and
      release steps. There is thus a need for methods to enhance the reversibility of
      biomolecular interactions. We have previously demonstrated that stimuli
      responsive polymers can be used to gate biomolecular reactions when conjugated
      near the active site of proteins. Here we have used a new smart polymer, N,N
      dimethyl acrylamide-co-4-phenylazophenylacrylate that has allowed a mechanistic
      investigation of the smart polymer switches. This polymer was conjugated via a
      vinyl sulfone terminus to cysteine residues of genetically engineered
      streptavidin mutant E116C, where the polymer is conjugated close to the biotin
      binding site, and streptavidin mutant S139C, where the conjugation site is
      distant. The biotin binding switching activity was strongly dependent on
      conjugation position, as the E116C conjugate displayed a large thermal response
      while the S139C conjugate displayed only small effects. Kinetic measurements of
      biotin release demonstrated that the off-rate of biotin was unperturbed and that
      the thermally triggered release of biotin with the E116C conjugate was due to the
      blocking the reassociation of biotin. The addition of free polymer to purified
      E116C conjugates was also shown to increase the blocking and release properties
      of the switch. This effect was site dependent, suggesting that the conjugated
      polymers were directing a physical aggregation near the binding site that
      effectively enhanced the switching activity. These investigations provide
      mechanistic insight that can be utilized to design better molecular switches for
      a variety of stimuli-responsive polymer-protein conjugates.

PMID- 11312695
TI  - An improved method for conjugating monoclonal antibodies with N
      hydroxysulfosuccinimidyl DOTA.
AB  - A simple, water-soluble procedure for conjugation of monoclonal antibodies to
      1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) has been
      improved by optimizing pH, buffer, and temperature conditions for the preparation
      of N-hydroxysulfosuccinimidyl DOTA and its conjugation to the human/murine
      chimeric anti-carcinoembryonic antigen antibody cT84.66. This improved method
      results in a 6-fold increase in conjugation efficiency, a 3-7-fold decrease in
      antibody cross-linking, a more homogeneous population of conjugate species, and a
      5-fold decrease in the quantities of reagents needed for conjugation. The cT84.66
      DOTA conjugate was labeled to high specific activity with 111In, 90Y, 88Y, 64Cu,
      and 67Cu, affording near-quantitative incorporation of the majority of these
      radiometals. This improved conjugation procedure facilitates large-scale
      production and radiometal labeling of cT84.66-DOTA for clinical
      radioimmunotherapy trials.

PMID- 11312696
TI  - Bacillus thuringiensis cry3Ca1 protein is toxic to the Colorado potato beetle,
      Leptinotarsa decemlineata (Say).
AB  - We expressed the wild-type cry3Aa3 and cry3Ca1 Bacillus thuringiensis genes,
      which code for insecticidal proteins, in an Escherichia coli expression system.
      Highly purified preparations of the soluble delta-endotoxins were used to perform
      comparative bioassays with third-instar larvae of the Colorado potato beetle
      (CPB). Acute mortality data showed that Cry3Ca1 (LD(50) = 320.1 ng) was 2-fold
      more toxic than Cry3Aa3 (LD(50) = 672.9 ng). We also compared the chronic effects
      of sublethal doses of these toxins by measuring the consumption of untreated
      foliage and monitoring survival and development for 6 days after intoxication. No
      significant additional mortality was recorded, but we found that surviving larvae
      fed Cry3Ca1 consumed foliage at a slower rate than the larvae fed Cry3Aa3,
      suggesting more damage to their digestive epithelium. This study, the first
      assessment of the toxicity of cry3Ca1 in third-instar CPB, suggests cry3Ca1 will
      prove useful for the control of this important insect pest.

PMID- 11312697
TI  - Metabolic control analysis of monoclonal antibody synthesis.
AB  - A general route for protein synthesis in eukaryotic cells has been proposed and
      applied to monoclonal antibody (MAb) synthesis. It takes into account
      transcription of the gene, binding of ribosomes to mRNA, and polypeptide
      elongation including binding to SRP (signal recognition particles) and SRP
      receptor, competing translocation, folding and glycosylation, assembly of the
      heavy and light chains in a tetrameric protein and Golgi processing and
      secretion. A comprehensive model was built on the basis of the proposed pathway.
      The model takes into account the mechanism of each step. Metabolic control
      analysis (MCA) principles were applied to the general pathway using the proposed
      model, and control coefficients were calculated. The results show a shared flux
      control (of both pathway flux and flux ratio at the branch) among different
      steps, i.e., transcription, folding, glycosylation, translocation and building
      blocks synthesis. The steps sharing the control depend on the concentration of
      building blocks, pathway flux and levels of OST (oligosacharyl transferase), BiP
      (heavy chain binding protein) and PDI (protein disulfide isomerase). Model
      predictions compare well with experimental data for MAb synthesis, explaining the
      control structure of the route and the heterogeneity of the product and also
      addressing future targets for improvement of the production rate of MAbs.

PMID- 11312698
TI  - A computational study of feedback effects on signal dynamics in a mitogen
      activated protein kinase (MAPK) pathway model.
AB  - Exploiting signaling pathways for the purpose of controlling cell function
      entails identifying and manipulating the information content of intracellular
      signals. As in the case of the ubiquitously expressed, eukaryotic mitogen
      activated protein kinase (MAPK) signaling pathway, this information content
      partly resides in the signals' dynamical properties. Here, we utilize a
      mathematical model to examine mechanisms that govern MAPK pathway dynamics,
      particularly the role of putative negative feedback mechanisms in generating
      complete signal adaptation, a term referring to the reset of a signal to
      prestimulation levels. In addition to yielding adaptation of its direct target,
      feedback mechanisms implemented in our model also indirectly assist in the
      adaptation of signaling components downstream of the target under certain
      conditions. In fact, model predictions identify conditions yielding ultra
      desensitization of signals in which complete adaptation of target and downstream
      signals culminates even while stimulus recognition (i.e., receptor-ligand
      binding) continues to increase. Moreover, the rate at which signal decays can
      follow first-order kinetics with respect to signal intensity, so that signal
      adaptation is achieved in the same amount of time regardless of signal intensity
      or ligand dose. All of these features are consistent with experimental findings
      recently obtained for the Chinese hamster ovary (CHO) cell lines (Asthagiri et
      al., J. Biol. Chem. 1999, 274, 27119-27127). Our model further predicts that
      although downstream effects are independent of whether an enzyme or adaptor
      protein is targeted by negative feedback, adaptor-targeted feedback can "back
      propagate" effects upstream of the target, specifically resulting in increased
      steady-state upstream signal. Consequently, where these upstream components serve
      as nodes within a signaling network, feedback can transfer signaling through
      these nodes into alternate pathways, thereby promoting the sort of signaling
      cross-talk that is becoming more widely appreciated.

PMID- 11312699
TI  - Impact of cell growth morphology on retroviral transduction: effect of contact
      inhibition.
AB  - Retrovirus-mediated gene transfer is one of the most commonly used methods to
      deliver, integrate, and express the gene of interest because the retrovirus can
      insert the desired gene into the chromosome of the target cells with high
      stability. However, to deliver the gene successfully, the retrovirus requires
      active division to integrate reversely transcribed DNA into the chromosome of
      target cells. In this study, we focused on the effect of cell-cell contact
      inhibition on the efficiency of retroviral transduction with two anchorage
      dependent cell lines: NIH 3T3 and 293 cells. These two cell lines have very
      different cell morphologies and growth patterns on surfaces. Human embryonic
      kidney epithelial 293 cells tend to stick together after dividing, while NIH 3T3
      cells migrate to occupy available surface and spread. Experimental data indicate
      that the abatement of the transduction rate of 293 cells was initiated in the
      early stage of the culture, whereas effect of contact inhibition of NIH 3T3 cells
      on the transduction rate became dominating at the end of the culture period.
      Experimental results were also quantitatively illustrated by plotting normalized
      multiplicity of infection (MOI) versus normalized cell density. According to the
      outcomes, cell inoculation density plays an important role in optimizing the
      retroviral transduction rate. The optimal time of retroviral transduction should
      be confined to the accelerating growth phase for 293 cells and at the exponential
      growth phase for NIH 3T3 cells. The implication drawn from this study is that
      contact inhibition effect on retroviral transduction should be taken into account
      for large-scale gene transfer systems such as the microcarrier bioreactor.

PMID- 11312700
TI  - Stable genetic transformation of Eschscholzia californica expressing synthetic
      green fluorescent proteins.
AB  - An efficient protocol is described for the stable genetic transformation of
      Eschscholzia californica (California poppy) using Agrobacterium tumefaciens as a
      vector. We have employed the disarmed A. tumefaciens LBA4404 encoding a synthetic
      green fluorescent protein reporter gene that is further controlled by an enhanced
      cauliflower mosaic virus 35S promoter. Stably transformed E. californica cells
      appear 3 weeks after initial cocultivation of A. tumefaciens with poppy leaves,
      stems, or roots. Transformed poppy calli were visualized by exposure to long-wave
      UV or blue light and analyzed in detail by fluorescent microscopy and laser
      scanning microscopy. Moreover, green fluorescent calli have been maintained
      through continual subculture and grow well either on Gamborg's B5 agarose or
      liquid medium.

PMID- 11312701
TI  - Effects of FIS overexpression on cell growth, rRNA synthesis, and ribosome
      content in Escherichia coli.
AB  - The Escherichia coli DNA binding protein FIS is a transcriptional modulator
      involved in the regulation of many cellular processes, including the activation
      of rRNA synthesis. High-level overproduction of FIS in early, mid, or late log
      cultures resulted in growth-phase- and media-specific variations in cell growth,
      rRNA synthesis, and ribosome content. FIS overproduction caused a pronounced
      increase in rRNA synthesis for late-exponential cultures but a substantial
      reduction in cell growth and ribosome content. The addition of simple sugars such
      as glucose or fructose reversed these phenomena, consistent with the functional
      role of FIS in carbon metabolism.

PMID- 11312702
TI  - Computer-aided control of water activity for lipase-catalyzed esterification in
      solvent-free systems.
AB  - A computer system for on-line monitoring and control of the water activity (a(w))
      in solvent-free media has been developed. The performance of this system was
      investigated by carrying out the lipase-catalyzed esterification of n-capric acid
      with n-decyl alcohol. A humidity sensor measured the relative humidity in the
      reactor headspace, which was then transmitted electrically to a digital computer
      that was used as a feedback controller. The water activity control was achieved
      by sparging either humidified air or dried air through the reaction medium at a
      flow rate determined by the digital feedback controller. The use of humid air and
      dry air for a(w) control made it possible to induce a larger a(w) gradient and
      thereby higher water transfer rate. As a result, the water activity quickly
      reached the desired a(w) values. We tested whether water activity in the reaction
      medium can be monitored by measuring relative humidity in the headspace. When the
      water activity in the liquid phase was determined from measurements of water
      content in the medium and compared to that measured directly with the humidity
      sensor, the a(w) in the reaction medium did not differ significantly from that in
      the headspace. This indicates that there is a near-equilibrium between the liquid
      medium and the exit air stream. Water activity was also successfully maintained
      close to the set point despite the massive production of water during the
      esterification process. Thus, the control system developed in this study is
      particularly useful for systems where large amounts of water are produced and
      where conventional methods make it difficult to control water activity as a
      result of a low water transfer rate. The effects that computer control of the
      water activity had on the reaction rate and yield were also examined. The
      reaction yield was significantly improved with water activity control. The
      conversions obtained at 28 h without and those with water activity control were
      70% and 96%, respectively. In addition, from the fact that the final yields
      increased with decreasing a(w), computer-aided water activity control was
      performed with a set-point change. By controlling a(w) at 0.55 during initial
      reaction phase, followed by a step change of a(w) from 0.55 to 0 after 11 h of
      reaction, it was possible to enhance the final conversion to 100%.

PMID- 11312703
TI  - Transfer of carbon dioxide within cultures of microalgae: plain bubbling versus
      hollow-fiber modules.
AB  - In attempts to improve the metabolic efficiency in closed photosynthetic
      reactors, availability of light and CO(2) are often considered as limiting
      factors, as they are difficult to control in a culture. The carbon source is
      usually provided via bubbling of CO(2)-enriched air into the culture medium;
      however, this procedure is not particularly effective in terms of mass transfer.
      Besides, it leads to considerable waste of that gas to the open atmosphere, which
      adds to operation costs. Increase in the interfacial area of contact available
      for gas exchange via use of membranes might be a useful alternative; microporous
      membranes, in hollow-fiber form, were tested accordingly. Two hollow-fiber
      modules, different in both hydrophilicity and outer surface area, were tested and
      duly compared, in terms of mass transfer, versus traditional plain bubbling.
      Overall volumetric coefficients (K(L)a) for CO(2) transfer were 1.48 x 10(-2)
      min(-1) for the hydrophobic membrane, 1.33 x 10(-2) min(-1) for the hydrophilic
      membrane, and 7.0 x 10(-3) min(-1) for plain bubbling. A model microalga, viz.
      Nannochloropsis sp., was cultivated using the two aforementioned membrane systems
      and plain bubbling. The produced data showed slight (but hardly significant)
      increases in biomass productivity when the hollow-fiber devices were used.
      However, hollow-fiber modules allow recirculation of unused CO(2), thus reducing
      feedstock costs. Furthermore, such indirect way of supplying CO(2) offers the
      additional possibility for use of lower gas pressures, as no need to
      counterbalance hydrostatic heads exists.

PMID- 11312704
TI  - Production of extracellular protease from crude substrates with dregs in an
      external-loop airlift bioreactor with lower ratio of height to diameter.
AB  - Bacillus subtilis AS1.398 was cultivated in a 11.5-L total volume external-loop
      airlift bioreactor with a low height-to-diameter ratio of 2.9 and a riser-to
      downcomer diameter ratio of 6.6 for the production of protease from crude
      substrates with dregs. The influence of aeration rate, liquid volume, and sparger
      hole diameter on protease production was investigated. An average of 8197 u/mL
      protease activity was obtained after a total fermentation time of 32 h in the
      external-loop airlift bioreactor with a liquid volume of 8.5 L, air flow rate of
      1.5 vvm, and sparger hole diameter of 1.5 mm. The addition of one stainless steel
      sieve plate in the riser of the airlift bioreactor increased productivity of
      protease. After 32 h of fermentation, an average of 8718 u/mL protease activity
      was achieved in the external-loop airlift bioreactor with one sieve plate and an
      air flow rate of 1.2 vvm, liquid volume of 8.5 L, and gas sparger hole diameter
      of 1.5 mm. This was 9.0% higher than the typical averages of about 8000 u/mL
      protease activity in the mechanically stirred tank bioreactors of the enzyme
      factory using the same microorganism. It is possible to make a scale-up of the
      external-loop airlift bioreactor and feasible to operate it for production of
      protease from crude substrate with dregs.

PMID- 11312705
TI  - Scale-up studies on a defined medium process for pilot plant production of
      illicicolin by Gliocladium roseum.
AB  - Illicicolin was cultivated at the 600-L pilot scale for purposes of material
      generation and process development. The initial medium containing oat flour was
      difficult operationally as a result of excessive foaming during sterilization, so
      a new defined medium process (with either glucose or sucrose as the carbon
      source), developed at the 23-L scale, was scaled up and improved for pilot scale
      needs. Pilot scale media development efforts focused on exploring the highest
      concentration of media (1.0 x to 3.0 x) that could be cultivated at the pilot
      scale and not be limited by mixing or oxygen mass transfer. The process was
      scaled up successfully and peak titers improved 7.5-fold, from about 200 mg/L in
      the initial complex medium to 1500 mg/L in the final defined medium.

PMID- 11312706
TI  - Detoxification of dilute acid hydrolysates of lignocellulose with lime.
AB  - The hydrolysis of hemicellulose to monomeric sugars by dilute acid hydrolysis is
      accompanied by the production of inhibitors that retard microbial fermentation.
      Treatment of hot hydrolysate with Ca(OH)(2) (overliming) is an effective method
      for detoxification. Using ethanologenic Escherichia coli LY01 as the biocatalyst,
      our results indicate that the optimal lime addition for detoxification varies and
      depends on the concentration of mineral acids and organic acids in each
      hydrolysate. This optimum was shown to be readily predicted on the basis of the
      titration of hydrolysate with 2 N NaOH at ambient temperature to either pH 7.0 or
      pH 11.0. The average composition of 15 hydrolysates prior to treatment was as
      follows (per L): 95.24 +/- 7.29 g sugar, 5.3 +/- 2.99 g acetic acid, 1.305 +/-
      0.288 g total furans (furfural and hydroxymethylfurfural), and 2.86 +/- 0.34 g
      phenolic compounds. Optimal overliming resulted in a 51 +/- 9% reduction of total
      furans, a 41 +/- 6% reduction in phenolic compounds, and a 8.7 +/- 4.5% decline
      in sugar. Acetic acid levels were unchanged. Considering the similarity of
      microorganisms, it is possible that the titration method described here may also
      prove useful for detoxification and fermentation processes using other microbial
      biocatalysts.

PMID- 11312707
TI  - Direct measurement of pH profiles in immobilized enzyme carriers during
      kinetically controlled synthesis using CLSM.
AB  - Confocal laser scanning microscopy was applied to measure the pH value in the
      carrier of immobilized enzymes during the enzyme-catalyzed synthesis. pH profiles
      with a high resolution are shown, with the pH increasing in the core of the
      particles. Significant differences occur for different carrier material, particle
      size, porosity and surface modification. The increased pH value is identified as
      one of the reasons leading to reduced enzyme selectivity in the penicillin
      amidase catalyzed synthesis of cephalosporins and penicillins.

PMID- 11312708
TI  - Asymmetric ketone reduction with immobilized yeast in hexane: biocatalyst
      deactivation and regeneration.
AB  - There is a need to develop methods for producing enantiomerically pure
      pharmaceuticals because the racemic mixtures made today will probably not be
      allowed in the future. Synthetic chiral catalysts are being developed for this
      purpose, as well as new product separation techniques. Another possible option is
      to use biocatalysts, such as purified enzymes or whole microbial cells, since
      these can result in the production of mostly a single enantiomer. This study
      emphasizes the use of alginate-entrapped yeast cells to catalyze the reduction of
      ketones as a model system. The emphasis is on the factors that might limit the
      reactivity of such cells, such as equilibrium conditions, substrate or product
      inhibition, solvent toxicity, loss of cell viability, or the degradation of
      intracellular levels of enzymes or cofactors. It was found that there was a
      progressive loss of catalytic activity of the immobilized yeast cells, which
      appeared to be mainly associated with a loss of cell viability and a decline of
      intracellular NAD(H) levels during the reaction. The other factors investigated
      did not have a large effect. A regeneration scheme was developed in order to
      replenish the intracellular NAD(H) lost during the reaction, which involved
      removing the biocatalyst from the reaction and supplying the cells with a
      nutrient source. This resulted in an increase in the NAD(H) to initial levels and
      also resulted in a maintenance of the ketone reduction rate over time.

PMID- 11312709
TI  - Optimization of fermentation conditions for preparation of polygalacturonic acid
      transeliminase by Erwinia carotovora IFO3830.
AB  - This paper is concerned with optimization of the fermentation conditions for
      preparation of alkaline pectin lyase (poly-galacturonic acid trans-eliminase,
      PATE) by Erwinia carotovora IFO3830 (E.C.IFO3830). The orthogonal matrix method
      was adopted as the experimental design method for media. The effects of media
      composition on the growth rate of E.C.IFO3830 are in the order of pectin >
      KH(2)PO(4)/Na(2)HPO(4) > MgSO(4) > (NH(4))(2)SO(4) > glucose > L-glutamate
      sodium, and those on PATE activity are in the order of glucose > pectin > L
      glutamate sodium > KH(2)PO(4)/Na(2)HPO(4) > MgSO(4) > (NH(4))(2)SO(4). The strain
      of E.C.IFO3830 grows quickly and easily near an initial pH of 7.0, and especially
      at the alkaline range of pH 7.0-8.0. The growth rate profiles indicate that
      E.C.IFO3830 grows very quickly; its generation time t(1/2) is about 0.2 h. The
      appropriate fermentation period is about 10-20 h for a high level productivity of
      biomass and 25-35 h for high productivity of PATE enzyme.

PMID- 11312710
TI  - Separation of pure and immunoreactive virus-like particles using gel filtration
      chromatography following immobilized metal ion affinity chromatography.
AB  - A purification process was developed to obtain highly pure rVP2H particles,
      formed by a structural protein (VP2) of the infectious bursal disease virus
      (IBDV) with six additional histidine residues at its C-terminus. The ultimate
      goal was the development of an efficient subunit vaccine against IBDV infection.
      The particles within the infected High-Five (Hi-5) cell lysates were partially
      purified by employing immobilized metal ion (Ni(2+)) affinity chromatography
      (IMAC). The initial step could recover approximately 85% of immunoreactive rVP2H
      proteins but failed to separate the rVP2H particles from the free rVP2H proteins
      or its degraded products. To separate the particulate form from the free form of
      rVP2H, an additional step was added, which used either gel filtration
      chromatography or CsCl density gradient ultracentrifugation. Both were able to
      produce extremely pure rVP2H particles with a buoyant density close to 1.27
      g/cm(3). However, the former method can process a larger sample volume than does
      the latter. By integrating IMAC and gel filtration chromatography, 1 mg of
      extremely pure rVP2H particles was routinely obtained from a 500 mL Hi-5 cell
      culture broth. The separation of the particulate form from the free form of rVP2H
      proteins exposes their respective immunogenicity to induce the virus-neutralizing
      antibodies and the ability to protect chickens from IBDV infection. Additionally,
      the abundant quantities of pure rVP2H particles coupled with their uniform
      dimensions facilitates an understanding of higher order structure of the
      immunogenic particles and can therefore result in improved vaccines against the
      virus.

PMID- 11312711
TI  - Comparison of different bioreactor systems for the production of high titer
      retroviral vectors.
AB  - Improved, human-based packaging cell lines allow the production of high-titer,
      RCR-free retroviral vectors. The utility of these cell lines for the production
      of clinical grade vectors critically depends on the definition of optimal
      conditions for scaled-up cultures. In this work, a clone derived from the TE Fly
      GALV packaging cell (Duisit et al. Hum. Gene Ther. 1999, 10, 189) that produces
      high titers of a lacZ containing retroviral vector with a Gibbon Ape Leukemia
      Virus envelope glycoprotein was used. This clone can produce (2-5) x 10(6) PFU
      cm(-3) in small scale cultures and has been evaluated for growth and vector
      production in different reactor systems. The performances of fixed bed reactors
      [CellCube (Costar) and Celligen (New Brunswick)] and stirred tank reactors
      [microcarriers and clump cultures] were compared. The cells showed a higher
      apparent growth rate in the fixed bed reactor systems than in the suspension
      systems, probably as a result of the fact that aggregation and/or formation of
      clumps led to a reduced viability and reduced growth of cells in the interior of
      the clumps. As a consequence, the final cell density and number were in average 3
      to 7-fold higher in the fixed bed systems in comparison to the suspension
      culture systems. The average titers obtained ranged from 0.5 to 2.1 x 10(7) PFU
      cm(-3) for the fixed bed and microcarrier systems, while the clump cultures
      produced only (2-5) x 10(5) PFU cm(-3). The differences in titers reflect cell
      densities as well as specific viral vector production rates, with the
      immobilization and microcarrier systems exhibiting an at least 10-fold higher
      production rate in comparison to the clump cultures. A partial optimization of
      the culture conditions in the Celligen fixed bed reactor, consisting of a 9-fold
      reduction of the seeding cell density, led to a 5-fold increased vector
      production rate accompanied by an average titer of 3 x 10(7) PFU cm(-3) (maximum
      titer (4-5) x 10(7) PFU cm(-3)) in the fixed bed reactor. The performance
      evaluation results using mathematical models indicated that the fixed bed
      bioreactor has a higher potential for retroviral vector production because of
      both the higher reactor productivity and the lower sensitivity of productivity in
      relation to the changes in final retrovirus titer in the range of 3 x 10(6) to 15
      x 10(6) PFU cm(-3).

PMID- 11312712
TI  - A quantitative approach to characterizing cell lysis caused by mechanical
      agitation of Streptomyces clavuligerus.
AB  - Streptomyces clavuligerus is a commercially important actinomycete that is used
      to produce clavulanic acid, a beta-lactamase inhibitor. Observations during 10
      batch cultivations with S. clavuligerus on defined media have led to the finding
      that the organism is very sensitive to shear when grown in batch cultures with
      increasing stirrer speed. The stirrer speed was increased to keep the dissolved
      oxygen level above 50% air saturation. A quantitative approach based on the
      calculation of elemental balances and a simple mathematical model is proposed to
      characterize the biomass lysis. Finally, a linear relation between biomass yield
      and observed specific growth rate is determined. Results show that cell lysis
      occurs at a high degradation rate, e.g., mu(max) = 0.16 h(-1) and k(d) = 0.07 h(
      1), when the gassed power input increases above 1.1, 1.7, or 2.0 kW/m(3),
      respectively, depending on the medium composition. The overall biomass yield on
      substrate is dramatically reduced in all experiments (>30%).

PMID- 11312713
TI  - Capillary electrophoresis as a method to study DNA reassociation.
AB  - To develop analytical methodology to assess the genetic complexity of a DNA
      sample, capillary electrophoresis with laser-induced fluorescence detection is
      used to monitor the annealing process of DNA samples. Coated columns are filled
      with an entangled polymer solution shown to optimally separate DNA through size
      selective capillary electrophoresis. DNA samples are denatured by heating in a
      boiling water bath for approximately 10 min and then cooled to approximately 25
      degrees C below the melting point of the DNA sample to initiate the reassociation
      process. The DNA is detected by means of the laser-induced fluorescence of
      intercalated ethidium bromide, which produces a substantially greater signal for
      double- versus single-stranded DNA. The rate of reassociation is dependent upon
      the rate at which complimentary strands of DNA encounter each other and the
      degree of repeating base sequences in the sample (hence, the diversity of the
      DNA). Experimental parameters also influence the reassociation rate. The effects
      of salt concentration and incubation temperature are presented. Traditional plots
      of C(o)t (C(o) = DNA concentration and t = reassociation time) versus % recovery
      of double-stranded DNA signal are generated for PhiX 174 Hae III digest and 50 bp
      stepladder DNA, individually and combined, to calculate the reassociation rate
      constants for these samples. Because reassociation of individual fragments is
      observed by the CE-LIF method, more information about the samples is available
      than with less specific and time-consuming traditional methods of investigating
      DNA reassociation.

PMID- 11312714
TI  - Supercritical fluids are superior media for catalysis by cross-linked enzyme
      microcrystals of subtilisin Carlsberg.
AB  - We report on the performance of cross-linked enzyme microcrystals (CLECs) of
      subtilisin Carlsberg in supercritical fluids (SC-fluids). The catalytic activity
      of CLECs in SC-ethane was found to be 2- to 10-fold greater than in hexane under
      the same conditions, using CLECs dried by propanol washing. Air-dried CLECs and
      lyophilized powders showed much lower activities, reflecting the same hydration
      hysteresis effects as in organic solvents. Reaction rates were much lower in SC
      CO(2), especially at higher water activity, probably as a result of acid-base
      effects of carbonic acid on the enzyme.

PMID- 11312715
TI  - Effects of culture conditions on enhancement of 2,4-dinitrotoluene degradation by
      Burkholderia engineered with the Vitreoscilla hemoglobin gene.
AB  - Growth and degradation of 2,4-dinitrotoluene (2,4-DNT) were compared in liquid
      cultures in shake flasks for Burkholderia sp. strain DNT and strain DNT
      engineered to produce Vitreoscilla (bacterial) hemoglobin (strain YV1).
      Parameters varied included aeration rate, initial 2,4-DNT concentration (50 and
      200 ppm), and concentration and type of cosubstrate (yeast extract, succinate,
      casamino acids, and tryptic soy broth). 2,4-DNT degradation increased with
      increasing cosubstrate concentration and was greater for strain YV1 than strain
      DNT under most conditions tested; the greatest advantages of YV1 (up to 3.5-fold)
      occurred under limited aeration. A third strain (YV1m), derived from YV1 by
      repeated growth on 2,4-DNT-containing medium, demonstrated increased 2,4-DNT
      degradation (up to 1.3-fold compared to YV1) at 200 ppm 2,4-DNT. The growth
      profiles of the three strains with respect to each other were in general similar
      to those of the degradation patterns of 2,4-DNT.

PMID- 11312716
TI  - Remarkable antiagglomeration effect of a yeast biosurfactant,
      diacylmannosylerythritol, on ice-water slurry for cold thermal storage.
AB  - Antiagglomeration effects of different surfactants on ice slurry formation were
      examined to improve the efficiency of an ice-water slurry system to be used for
      cold thermal storage. Among the chemical surfactants tested, a nonionic
      surfactant, poly(oxyethylene) sorbitan dioleate, was found to show a greater
      antiagglomeration effect on the slurry than anionic, cationic, or amphoteric
      surfactants. More interestingly, diacylmannosylerythritol, a glycolipid
      biosurfactant produced by a yeast strain of Candida antarctica, exhibited a
      remarkable effect on the slurry, attaining a high ice packing factor (35%) for 8
      h at a biosurfactant concentration of 10 mg/L. These nonionic glycolipid
      surfactants are likely to effectively adsorb on the ice surface in a highly
      regulated manner to suppress the agglomeration or growth of the ice particles.
      This is the first report on the utilization of biosurfactant for thermal energy
      storage, which may significantly expand the commercial applications of the highly
      environmentally friendly slurry system.

PMID- 11312717
TI  - Optimization of conditions for bacteriocin extraction in PEG/salt aqueous two
      phase systems using statistical experimental designs.
AB  - The bacteriocin nisin was extracted in PEG/salt aqueous two-phase systems (ATPS)
      using the property that the systems can extract hydrophobic proteins. The
      concentrations of the phase-forming components, PEG 4000 and Na(2)SO(4), were
      optimized for nisin recovery by means of statistical experimental designs, and it
      was found that they strongly influenced nisin recovery. The optimal composition
      of ATPS was found to be 15.99% (w/w) PEG 4000 and 15.85% (w/w) Na(2)SO(4) (pH 2),
      and the optimal ATPS allowed an 11.60% increase of nisin recovery compared to the
      standard method of nisin assay.

PMID- 11312718
TI  - Latex particles with thermo-flocculation and magnetic properties for
      immobilization of alpha-chymotrypsin.
AB  - Core-shell-type latex particles composed of styrene, N-isopropylacrylamide
      (NIPAAm), and N-acryloxysuccinimide (NAS) were synthesized by surfactant-free
      emulsion polymerization. The latex particles show thermo-flocculation behavior
      due to the presence of temperature-sensitive monomer NIPAAm and could be used for
      immobilization of alpha-chymotrypsin through covalent bonding with the reactive
      ester groups of NAS. Enzyme recycle could be accomplished in this immobilized
      enzyme system by sedimentation of the thermo-flocculated latex particles in 20
      min at 30 degrees C by raising the salt (NaCl) concentration to 0.5 M. To further
      enhance the sedimentation rate, ultrafine magnetite particles were prepared and
      included during polymerization to produce magnetic temperature-sensitive latex
      particles (MTLP), which could be recovered 6 times faster after thermo
      flocculation by applying a low magnetic field. However, a higher salt
      concentration was necessary to flocculate the MTLP under the same condition as a
      result of its increased surface hydrophilicity, which originates from different
      polymerization conditions and the incorporation of magnetite. The immobilized
      enzyme shows high activity even against macromolecular substrates (hemoglobin and
      casein) owing to limited diffusion resistance, with full activity retention for
      nonmagnetic latex but one-half reduction in activity if the magnetic property was
      introduced. Optimal enzyme immobilization pH and enzyme loading were determined,
      and properties of the immobilized enzyme were characterized. The immobilized
      enzyme was used in 10 repeated batch hydrolyses of casein with successive
      flocculation/dispersion cycles and showed less than 15% activity decrease at the
      end. Overall, introducing the magnetic property to the latex could effectively
      enhance the solid-liquid separation rate after thermo-flocculation and maintain
      enzyme activity after repeated use but adversely influence the activity of the
      immobilized enzyme.

PMID- 11312719
TI  - Simultaneous measurement of 19 components in serum-containing animal cell culture
      media by fourier transform near-infrared spectroscopy.
AB  - Animal cell cultures generate maximal amounts of desired products when maintained
      in a controlled environment with low and constant concentrations of nutrients and
      wastes. Traditionally this has involved slow addition of glucose and glutamine;
      however, recent studies have indicated that a number of low concentration amino
      acids are required to prevent initiation of apoptosis. Therefore, optimal control
      of animal cell cultures will likely require measurement of a large number of
      chemical components. We present here the evaluation of a near-infrared
      spectroscopic (NIRS) monitoring scheme to quantify 19 cellular nutrients and
      wastes in culture medium with and without serum. The components include glucose,
      lactate, ammonia, pyruvate, glutamine, and 14 other amino acids. Spectroscopic
      calibrations were generated for a synthetic version of a standard culture medium
      (DMEM) in which the concentrations of 17 DMEM components and ammonia and lactate
      were varied in a random fashion. This randomization provides a stringent
      evaluation of the measurement scheme. Reasonably accurate measurements of these
      19 components could be accomplished in the absence or presence of 10% horse serum
      by volume with percent errors ranging from 3% to 37%. Analytes with
      concentrations as low as 0.3 mM could be reliably quantified. The presence of
      serum, when properly included in the calibration, has little effect on
      measurement error. These results provide an important step toward application of
      NIRS for monitoring the large number of varying components of animal cell
      cultivations.

PMID- 11312720
TI  - Enzymatic hydrolysis of waste office paper using viscosity as operating
      parameter.
AB  - Enzymatic hydrolysis of waste office (WO) paper with feeding WO paper in a
      reactor was investigated using apparent viscosity as operating parameter. Since
      the apparent viscosity was correlated with the concentration of pulping WO paper,
      the amount of hydrolyzed WO paper was assumed by measuring the decrease in the
      apparent viscosity. Then the amount of hydrolysis WO paper and the amount of
      enzyme corresponding to the desired ratio were fed into the reactor. When the WO
      paper and 1% (to the amount of WO paper) enzyme were fed to the hydrolytic
      reaction, 87 g/L of reducing sugar (RS) with a hydrolytic yield of 42.2% was
      obtained for a 24-h hydrolysis. However, when nonpulping WO paper and 5% (to the
      amount of WO paper) enzyme were fed to the hydrolytic reaction, 120 g/L of RS
      with a hydrolytic yield of 40% was obtained for a 24-h hydrolysis. Therefore, the
      RS concentration from this hydrolysis process feeding WO paper using apparent
      viscosity as operating parameter may be of sufficient concentration to serve as a
      carbon source in microorganism culture or chemical feedstock.

PMID- 11312722
TI  - Hydrothermal dehydration of precipitates: convenient synthesis method for solids.

PMID- 11312723
TI  - Structure and magnetic properties of a pyrophosphate-bridged Cu(II) complex.

PMID- 11312724
TI  - Mechanism of oxidative addition of mercury(II) compounds to platinum(II).

PMID- 11312725
TI  - Missing hydrogens in B(19)H(20)(-)? Application of electron counting rule for
      edge-sharing macropolyhedral boranes.

PMID- 11312726
TI  - An intramolecular disproportionation reaction leading to the formation of the
      quadruply bonded complex Cl(4)ReReCl(2)(dppf) (dppf = 1,1'
      bis(diphenylphosphino)ferrocene). An example of the missing 1,3
      Re(2)Cl(6)(PR(3))(2) isomer.

PMID- 11312727
TI  - Synthesis, pH-dependent structural characterization, and solution behavior of
      aqueous aluminum and gallium citrate complexes.
AB  - Reactions of Al(III) and Ga(III) with citric acid in aqueous solutions, yielded
      the complexes (NH(4))(5)[M(C(6)H(4)O(7))(2)].2H(2)O (M(III) = Al (1), Ga (2)) at
      alkaline pH, and the complexes (Cat)(4)[M(C(6)H(5)O(7))(C(6)H(4)O(7))].nH(2)O
      (M(III) = Al (3), Ga (4), Cat. = NH(4)(+), n = 3; M(III) = Al (5), Ga (6), Cat. =
      K(+), n = 4) at acidic pH. All compounds were characterized by spectroscopic (FT
      IR, (1)H, (13)C, and (27)Al NMR, (13)C-MAS NMR) and X-ray techniques. Complex 1
      crystallizes in space group P1, with a = 9.638(5) A, b = 9.715(5) A, c = 7.237(4)
      A, alpha = 90.96(1) degrees, beta = 105.72(1) degrees, gamma = 119.74(1) degrees,
      V = 557.1(3) A(3), and Z = 1. Complex 2 crystallizes in space group P1, with a =
      9.659(6) A, b = 9.762(7) A, c = 7.258(5) A, alpha = 90.95(2) degrees, beta =
      105.86(2) degrees, gamma = 119.28(1) degrees, V = 564.9(7) A(3), and Z = 1.
      Complex 3 crystallizes in space group I2/a, with a = 19.347(3) A, b = 9.857(1) A,
      c = 23.412(4) A, beta = 100.549(5) degrees, V = 4389(1) A(3), and Z = 8. Complex
      4 crystallizes in space group I2/a, with a = 19.275(1) A, b = 9.9697(6) A, c =
      23.476(1) A, beta = 100.694(2) degrees, V = 4432.8(5) A(3), and Z = 8. Complex 5
      crystallizes in space group P1, with a = 7.316(1) A, b = 9.454(2) A, c = 9.569(2)
      A, alpha = 64.218(4) degrees, beta = 69.872(3) degrees, gamma = 69.985(4)
      degrees, V = 544.9(2) A(3), and Z = 1. Complex 6 crystallizes in space group P1,
      with a = 7.3242(2) A, b = 9.4363(5) A, c = 9.6435(5) A, alpha = 63.751(2)
      degrees, beta = 70.091(2) degrees, gamma = 69.941(2) degrees, V = 547.22(4) A(3),
      and Z = 1. The crystal structures of 1-6 reveal mononuclear octahedral complexes
      of Al(III) (or Ga(III)) bound to two citrates. Solution NMR, on both 4- and 5-
      species, reveals rapid intramolecular exchange of the bound and unbound terminal
      carboxylates. Upon dissolution in water, the complexes, through a complicated
      reaction cascade, transform to oligonuclear 1:1 species that, in agreement with
      previous studies, represent the thermodynamically stable state in solution. The
      data provide, for the first time, structural details of low MW, mononuclear
      complexes of Al(III) (or Ga(III)) with citrate that are dictated, among other
      factors, by pH. The properties of 1-6 may provide clues relevant to their
      biological association with humans.

PMID- 11312728
TI  - Synthesis, characterization, and reactivity of trans-[PtCl(R'R''SO)(A)2]NO3
      (R'R''SO = Me2SO, MeBzSO, MePhSO; A= NH3, py, pic). Crystal structure of trans
      [PtCl(Me2SO)(py)2]+.
AB  - Trans complexes such as trans-[PtCl(2)(NH(3))(2)] have historically been
      considered therapeutically inactive. The use of planar ligands such as pyridine
      greatly enhances the cytotoxicity of the trans geometry. The complexes trans
      [PtCl(R'R''SO)(A)(2)]NO(3) (R'R''SO = substituted sulfoxides such as dimethyl
      (Me(2)SO), methyl benzyl (MeBzSO), and methyl phenyl sulfoxide (MePhSO) and A =
      NH(3), pyridine (py) and 4-methylpyridine or picoline (pic)) were prepared for
      comparison of the chemical reactivity between ammine and pyridine ligands. The X
      ray crystal structure determination for trans-[PtCl(Me(2)SO)(py)(2)]NO(3)
      confirmed the geometry with S-bound Me(2)SO. The crystals are orthorhombic, space
      group P2(1)2(1)2(1), with cell dimensions a = 7.888(2) A, b = 14.740(3) A, c
      =15.626(5) A, and Z = 4. The geometry around the platinum atom is square planar
      with l(Pt-Cl) = 2.304(4) A, l(Pt-S) = 2.218(5) A, and l(Pt-N) = 2.03(1) and
      2.02(1) A. Bond angles are normal with Cl-Pt-S = 177.9(2) degrees, Cl-Pt-N(1) =
      88.0(4) degrees, Cl-Pt-N(2) = 89.3(5) degrees, S-Pt-N(1) = 93.8(4) degrees, S-Pt
      N(2) = 88.9(4) degrees, and N(1)-Pt-N(2) = 177.2(6) degrees. The intensity data
      were collected with Mo Kalpha radiation with lambda = 0.710 69 A. Refinement was
      by full-matrix least-squares methods to a final R value of 3.80%. Unlike trans
      [PtCl(2)(NH(3))(2)], trans-[PtCl(2)(A)(2)] (A = py or pic) complexes do not react
      with Me(2)SO. The solvolytic products of cis-[PtCl(2)(A)(2)] (A = py or pic) were
      characterized. Studies of displacement of the sulfoxide by chloride were
      performed using HPLC. The sulfoxide was displaced faster for the pyridine complex
      relative to the ammine complex. Chemical studies comparing the reactivity of
      trans-[PtCl(R'R''SO)(amine)(2)]NO(3) with a model nucleotide, guanosine 5'
      monophosphate (GMP), showed that the reaction gave two principal products: the
      species [Pt(R'R''SO)(amine)(2)(N7-GMP)], which reacts with a second equivalent of
      GMP, forming [Pt(amine)(2)(N7-GMP)(2)]. The reaction pathways were different,
      however, for the pyridine complexes in comparison to the NH(3) species, with
      sulfoxide displacement again being significantly faster for the pyridine case.

PMID- 11312729
TI  - Synthesis and single-crystal x-ray diffraction examination of a structurally
      homologous series of tetracoordinate heteroleptic anionic lanthanide complexes:
      Ln[N[Si(CH3)2CH2CH2Si(CH3)2]]3(mu-Cl)Li(L)3 (Ln = Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm,
      Yb; (L)3 =(THF)3, (Et2O)3, (THF)2(Et2O)].
AB  - Anhydrous lanthanide(III) chlorides (Ln = Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb)
      react with 3 equiv of lithium 2,2,5,5-tetramethyl-2,5-disila-1-azacyclopentanide,
      Li[N[Si(CH3)2CH2Ch2Si(CH3)2]], in THF or Et(2)O to afford the monomeric four
      coordinate heteroleptic ate complexes Ln[N[Si(CH3)2CH2CH2Si(CH3)2]]3(mu
      Cl)Li(THF/Et2O)3 (Ln = Sm (1), Eu (2), Gd (3), Tb (4), Dy (5), Ho (6), Er (7), Tm
      (8), Yb (9)), whose solid-state structures were determined by the single-crystal
      X-ray diffraction technique. All complexes additionally were characterized by
      melting point determination, elemental analyses, and mass spectrometry.

PMID- 11312730
TI  - Effective monkey saddle points and berry and lever mechanisms in the
      topomerization of SF(4) and related tetracoordinated AX(4) species.
AB  - The topomerization mechanisms of the SF(4) and SCl(2)F(2) sulfuranes, as well as
      their higher (SeF(4), TeF(4)) and isoelectronic analogues PF(4)(-), AsF(4)(-),
      SbF(4)(-), SbCl(4)(-), ClF(4)(+), BrF(4)(+), BrCl(2)F(2)(+), and IF(4)(+)), have
      been computed at B3LYP/6-31+G and at B3LYP/6-311+G. All species have trigonal
      bipyramidal (TBP) C(2)(v)() ground states. In such four-coordinated molecules,
      Berry rotation exchanges both axial with two equatorial ligands simultaneously
      while the alternative "lever" mechanism exchanges only one axial ligand with one
      equatorial ligand. While the barrier for the lever exchange in SF(4) (18.8 kcal
      mol(-1)) is much higher than that for the Berry process (8.1 kcal mol(-1)), both
      mechanisms are needed for complete ligand exchange. The F(ax)F(ax) and F(eq)F(eq)
      isomers of SF(2)Cl(2) have nearly the same energy and readily interconvert by BPR
      with a barrier of 7.6 kcal mol(-1). The enantiomerization of the F(ax)F(eq)
      chiral isomer can occur by either the Berry process (transition state barrier 8.3
      kcal mol(-1)) or the "lever" mechanism via either of two C(s)() transition
      states, based on the TBP geometry: Cl(ax) <--> Cl(eq) or F(ax) <--> F(eq)
      exchanges with barriers of 6.3 and 15.7 kcal mol(-1), respectively. Full
      scrambling of all ligand sites is possible only by inclusion of the lever
      mechanism. Planar, "tetrahedral", and triplet forms are much higher in energy.
      The TBP C(3)(v) structures of AX(4) either have two imaginary frequencies (NIMAG
      = 2) for the X = F, Cl species or are minima (NIMAG = 0) for the X = Br, I
      compounds. These "effective monkey saddle points" have degenerate modes with two
      small frequencies, imaginary or real. Although a strictly defined "monkey saddle"
      (with degenerate frequencies exactly zero) is not allowed, the flat C(3)(v)
      symmetry region serves as a "transition state" for trifurcation of the pathways.
      The BPR mechanism also is preferred over the alternative lever process in the
      topomerization of the selenurane SeF(4) (barriers 5.9 vs. 12.1 kcal mol(-1)), the
      tellurane TeF(4) (2.1 vs. 6.4), and the interhalogen cations ClF(4)(+) (2.5 vs
      14.8), BrF(4)(+) (4.7 vs. 11.3), BrF(2)Cl(2)(+) (14.6 vs. 17.4), and IF(4)(+)
      (1.4 vs. 6.0), as well as for the series PF(4)(-) (7.0 vs. 9.0), AsF(4)(-) (9.3
      vs. 17.2), and SbF(4)(-) (3.8 vs. 5.3 kcal mol(-1)), all computed at B3LYP/6
      311+G with the inclusion of quasirelativistic pseudopotentials for Te, I, and Sb.
      The heavier halogens increasingly favor the lever process, where the barrier (2.6
      kcal mol(-1)) pertaining to the effective monkey saddle point (C(3)(v) minimum
      for SbCl(4)(-)) is less than that for the Berry process (8.2 kcal mol(-1)).

PMID- 11312731
TI  - Syntheses of the first amine-dicarboxyboranes and their bis(methylester) and
      bis(N-ethylamide) derivatives.
AB  - Amine-bis(N-ethylcarbamoyl)boranes [A.BH(CONHEt)(2), 3; A = trimethylamine
      (Me(3)N, a), quinuclidine (Q, b), pyridine (py, f), 4-picoline (pic, g)] have
      been prepared after deprotonation of [amine-bis(C-hydroxy-N
      ethylimidate)hydroboron(2+)] cations (2), which were formed by the hydrolysis of
      [amine-bis(ethylnitrilium)hydroboron(2+)]tetrafluoroborates (1). Numerous
      representatives of 3 [A = diethylamine (Et(2)NH, c), piperidine (pip, d),
      pyrrolidine (pyrr, e), 4-aminopyridine (4-NH(2)-py, h), 4-(dimethylamino)pyridine
      (DMAP, i), imidazole (Him, j), 1-methylimidazole (Mim, k)] have been prepared by
      base exchange reactions from 3a. 3a-e are extremely stable in aqueous media,
      either acidic or alkaline, probably because of the considerable steric hindrance
      of possible reaction centers. However, they were transformed into amine
      dicarboxyboranes [A.BH(COOH)(2), 4a-e] in acidic medium under vigorous conditions
      (100-130 degrees C). This transformation was accompanied by significant
      decomposition, probably owing to the protonation on the N atom, resulting in the
      rupture of the B-N bond. As an exception, 4b, where N atom in a rigid bicycle is
      not prone to attacks, could be isolated in very good yield. On the other hand,
      amine-bis(N-ethylcarbamoyl)boranes containing amines with sp(2)-hybridized N
      atoms (3f-k) undergo complete decomposition under similar conditions probably
      because of the increased hydridic character of the hydrogen adjacent to boron.
      Base exchange reactions starting from 4b resulted in the ammonium salts of 4c-e,
      h, i of composition [A.BH(COOH)(COO(-))][AH(+)], which in turn could be
      transformed into the diacids 4, except 4h, by protonation. As salt formation
      indicates, the 4 compounds are stronger acids as univalent acids than the
      corresponding A.BH(2)(COOH) complexes. 4a-e, i were readily esterified into amine
      bis(methoxycarbonyl)boranes (5a-e, i) in methanol, employing a catalytic amount
      of HBr. 5a-e, i are stable in alkaline medium but are readily hydrolyzed in
      acidic medium. Hydrolysis of [amine-bis(C-methoxy-N-ethylimidate)hydroboron(2+)]
      cations did not give the corresponding bisesters 5 in alkaline, neutral, or
      acidic medium.

PMID- 11312732
TI  - Computer-aided design (CAD) of Mn(II) complexes: superoxide dismutase mimetics
      with catalytic activity exceeding the native enzyme.
AB  - New Mn(II) macrocyclic pentaamine complexes derived from the biscyclohexyl
      pyridine complex, M40403 ([manganese(II)dichloro[(4R,9R,14R,19R)-3,10,13,20,26
      pentaazatetracyclo[20.3.1.0.(4,9)0(14,19)]hexacosa-1(26),-22(23),24-triene]]),
      are described here. The complex M40403 was previously shown to be a superoxide
      dismutase (SOD) catalyst with rates for the catalytic dismutation of superoxide
      to oxygen and hydrogen peroxide at pH = 7.4 of 1.2 x 10(+7) M(-1) s(-1).(1) The
      use of the computer-aided design paradigm reported previously for this class of
      Mn(II) complexes(2,3) led to the prediction that the 2S,21S-dimethyl derivative
      of M40403 should possess superior catalytic SOD activity. The synthesis of this
      new macrocyclic Mn(II) complex, [manganese(II)dichloro[2S, 21S-dimethyl
      (4R,9R,14R,19R)-3,10,13,20,26-pentaazatetracyclo[20.3.1.0.(4,9)0(14,19)]hexacosa
      1(26),22(23),24-triene]], 5, was accomplished via a high yield template
      condensation utilizing the linear tetraamine, N,N'-Bis[(1R,2R)-[2
      (amino)]cyclohexyl]-1,2-diaminoethane, 1, 2,6-diacetylpyridine, and MnCl(2) to
      form the macrocyclic diimine complex, 2, which then is reduced. The two other
      possible dimethyl diastereomers of 5 (2R,21R-dimethyl,3, and 2R,21S-dimethyl, 6)
      were also prepared via reduction of the diimine complex 2. Two of these
      complexes, 3 and 5, were characterized by X-ray structure determination
      confirming their absolute stereochemistry as 2R,21R-dimethyl and 2S,21S-dimethyl,
      respectively. The results of the MM calculations which predict that the 2S,21S
      dimethyl complex, 5, should be a high activity catalyst and that the 2R,21R
      dimethyl complex, 3, should have little or no catalytic activity are presented.
      The catalytic SOD rates for these complexes are reported for each of these
      complexes and a correlation with the modeling predictions is established showing
      that 2R,21R-complex, 3, has no measurable catalytic rate, while the 2R,21S
      complex, 6, is identical to M40403, and the 2S,21S- complex, 5, possesses a very
      fast rate at pH = 7.4 of 1.6 x 10(+9) M(-1) s(-1) exceeding that of the native
      mitochondrial MnSOD enzymes.

PMID- 11312733
TI  - Empirical and ab initio energy/architectural patterns for 73 nido-6<V>-carborane
      isomers, from B(6)H(9)(-) to C(4)B(2)H(6).
AB  - Qualitative rules governing carbon and bridge-hydrogen placement permit the
      prediction of the most stable isomeric structures for the various carboranes.
      Seventy-three isomeric boron hydride and carborane structures, from B(6)H(9)(-)
      to C(4)B(2)H(6), were computed at the ab initio MP2(fc)/6-31G level to determine
      their relative stabilities quantitatively. Specific architectural features,
      recognized to be unfavorable, were assigned "energy penalty" values that allow
      the projection of comprehensive thermodynamic stability values via a simple
      additivity procedure. These values match the ab initio results with surprising
      precision. Our study includes Siebert's nido-2,3,5-C(3)B(3)H(7) and Wrackmeyer's
      nido-2,4-C(2)B(4)H(8) nido-6<V> carboranes, which contain "unusual" CH-B-bridge
      hydrogens.

PMID- 11312734
TI  - New silylated iminophosphorano(amino)phosphines Me(3)SiN=PPh(2)N(R)PPh(2) (R =
      Et, (n)Pr, (n)Bu). Crystal and molecular structure of
      trimethylsilyliminophosphorano(propylamino)diphenylphosphine
      Me(3)SiN=PPh(2)N((n)Pr)PPh(2). Further oxidative derivatization with S, Se, and
      azides, titanium(IV) transmetalation of the imine, and syntheses of rhodium(I),
      palladium(II), and platinum(II) complexes of these
      iminophosphorano(amino)phosphines.
AB  - Bis(phosphino)amines Ph(2)PN(R)PPh(2) (R = Et, (n)Pr, (n)Bu) react with
      stoichiometric amounts of trimethylsilyl azide to give the
      trimethylsilyliminophosphorano(amino)phosphines Me(3)SiN=PPh(2)N(R)PPh(2) (1, R =
      Et; 2, R = (n)Pr; 3, R = (n)Bu) as crystalline compounds. The structure of 2 has
      been determined by single-crystal X-ray analysis. (Crystal data for 2:
      monoclinic, P2(1)/c, a = 10.235(1) A, b = 16.802(2) A, c = 17.075(2) A, beta =
      101.05(1) degrees, V = 2882.9(5) A(3), Z = 4.) The structure of 2, which is the
      first example of an iminophosphoranophosphine with the P(III)-N-P(V)=N skeleton,
      was solved by direct methods and refined to R = 0.044. Compound 2 readily reacts
      with elemental sulfur, selenium, or phosphoryl azide to give fully oxidized
      phosphinimines Ph(2)P(E)N((n)()Pr)Ph(2)P=NSiMe(3) (4, E = S; 5, E = Se; 6, E =
      NP(O)(OPh)(2)). Compounds 4-6 are very sensitive to moisture and readily undergo
      desilylation to give the parent phosphinimines Ph(2)P(E)N((n)()Pr)Ph(2)P=NH,
      which can be isolated as moderately stable crystalline solids. The
      phosphiniminophosphine 2 and the oxidized phosphinimines (4 and 5) react with
      CpTiCl(3) to give new nitrogen-bound Ti(IV) derivatives
      Ph(2)P(E)N((n)Pr)Ph(2)P=NTi(Cp)Cl(2) (10, E = lone pair; 11, E = S; 12, E = Se).
      Compounds 1-3 readily react with rhodium(I), palladium(II), and platinum(II)
      complexes to give five-membered metallacycles via phosphorus(III) and imine
      nitrogen coordination.

PMID- 11312735
TI  - Synthesis and characterization of the silver maleonitrilediselenolates and silver
      maleonitriledithiolates [K([2.2.2]-cryptand)]4[Ag4(Se2C2(CN)2)4], [Na([2.2.2]
      cryptand)]4[Ag4(S2C2(CN)2)4].0.33MeCN, [NBu4]4[Ag4(S2C2(CN)2)4], [K([2.2.2]
      cryptand)]3[Ag(Se2C2(CN)2)2].2MeCN, and [Na([2.2.2]-cryptand)]3[Ag(S2C2(CN)2)2].
AB  - Reaction of AgBF(4), KNH(2), K(2)Se, Se, and [2.2.2]-cryptand in acetonitrile
      yields [K([2.2.2]-cryptand)](4)[Ag(4)(Se(2)C(2)(CN)(2))(4)] (1). In the unit cell
      of 1 there are four [K([2.2.2]-cryptand)](+) units and a tetrahedral Ag(4)
      anionic core coordinated in mu(1)-Se, mu(2)-Se fashion by each of four mns
      ligands (mns = maleonitrilediselenolate, [Se(2)C(2)(CN)(2)](2)(-)). Reaction of
      AgNO(3), Na(2)(mnt) (mnt = maleonitriledithiolate, [S(2)C(2)(CN)(2)](2)(-)), and
      [2.2.2]-cryptand in acetonitrile yields [Na([2.2.2]
      cryptand)](4)[Ag(4)(mnt)(4)].0.33MeCN (2). The Ag(4) anion of 2 is analogous to
      that in 1. Reaction of AgNO(3), Na(2)(mnt), and [NBu(4)]Br in acetonitrile yields
      [NBu(4)](4)[Ag(4)(mnt)(4)] (3). The anion of 3 also comprises an Ag(4) core
      coordinated by four mnt ligands, but the Ag(4) core is diamond-shaped rather than
      tetrahedral. Reaction of [K([2.2.2]-cryptand)](3)[Ag(mns)(Se(6))] with KNH(2) and
      [2.2.2]-cryptand in acetonitrile yields [K([2.2.2]
      cryptand)](3)[Ag(mns)(2)].2MeCN (4). The anion of 4 comprises an Ag center
      coordinated by two mns ligands in a tetrahedral arrangement. Reaction of AgNO(3),
      2 equiv of Na(2)(mnt), and [2.2.2]-cryptand in acetonitrile yields [Na([2.2.2]
      cryptand)](3)[Ag(mnt)(2)] (5). The anion of 5 is analogous to that of 4.
      Electronic absorption and infrared spectra of each complex show behavior
      characteristic of metal-maleonitriledichalcogenates. Crystal data (153 K): 1,
      P2/n, Z = 2, a = 18.362(2) A, b = 16.500(1) A, c = 19.673(2) A, beta = 94.67(1)
      degrees, V = 5941(1) A(3); 2, P4, Z = 4, a= 27.039(4) A, c = 15.358(3) A, V =
      11229(3) A(3); 3, P2(1)/c, Z = 6, a = 15.689(3) A, b = 51.924(11) A, c =
      17.393(4) A, beta = 93.51(1) degrees, V = 14142(5) A(3); 4, P2(1)/c, Z = 4, a =
      13.997(1) A, b = 21.866(2) A, c = 28.281(2) A, beta = 97.72(1) degrees, V =
      8578(1) A(3); 5, P2/n, Z = 2, a = 11.547(2) A, b = 11.766(2) A, c = 27.774(6) A,
      beta = 91.85(3) degrees, V = 3772(1) A(3).

PMID- 11312736
TI  - Synthesis and structural characterization of a new series of vanadoselenites,
      [Se(x)V(4-x)O(12-x)](4-x)- (x=1,2).
AB  - Two new vanadoselenites, [SeV(3)O(11)](3)(-) and [Se(2)V(2)O(10)](2)(-), were
      synthesized by reacting SeO(2) with VO(3)(-). Single-crystal X-ray structural
      analyses of [(n-C(4)H(9))(4)N](3)[SeV(3)O(11)].0.5H(2)O [orthorhombic, space
      group P2(1)2(1)2, a = 22.328(5) A, b = 44.099(9) A, c = 12.287(3) A, Z = 8] and
      [[(C(6)H(5))(3)P](2)N](2)[Se(2)V(2)O(10)] [monoclinic, space group P2(1)/n, a =
      12.2931(3) A, b = 13.5101(3) A, c = 20.9793(5) A, beta = 106.307(1) degrees, Z =
      2] revealed that both anions are composed of Se(x)()V(4)(-)(x)()O(4) rings. The
      (51)V, (77)Se, and (17)O NMR spectra established that both [SeV(3)O(11)](3)(-)
      and [Se(2)V(2)O(10)](2)(-) anions maintain this ring structure in solution.

PMID- 11312737
TI  - Spectroscopy of UO(2)Cl(4)(2)(-) in basic aluminum chloride-1-ethyl-3
      methylimidazolium chloride.
AB  - The optical absorption, emission, FT Raman, one-photon excitation, two-photon
      excitation, and luminescence lifetime measurements are reported for
      UO(2)Cl(4)(2)(-) in 40:60 AlCl(3)-EMIC (where EMIC identical with 1-ethyl-3
      methylimidazolium chloride), a room-temperature ionic liquid. Comparison of the
      spectra with previous results from single crystals containing UO(2)Cl(4)(2)(-)
      allowed the characterization of four ground-state vibrational frequencies, two
      excited-state vibrational frequencies, and the location of eight electronic
      excited-state energy levels. The vibrational frequencies and electronic energy
      levels are found to be consistent with the UO(2)Cl(4)(2)(-) ion. Comparison of
      the one-photon and two-photon excitation spectra, and the relative intensities of
      the transitions in the emission spectrum indicate that the center of symmetry is
      perturbed by an interaction with the solvent.

PMID- 11312738
TI  - Molecular tricorns: self-assembly of trinuclear palladium(II) complexes.
AB  - Cyclometalation of the ligand 1,3-bis(1-alkylbenzimidazol-2-yl)benzene (1) with
      palladium carboxylates leads to a trimeric complex
      [Pd(3)(ligand)(3)(carboxylate)(3)] (3). Studies in solution show that the
      trinuclear core is stable but that the carboxylates are labile, undergoing intra-
      and intermolecular exchange on an NMR time scale. The structural analogue of 1,
      2,6-bis(1-alkylbenzimidazol-2-yl)pyridine (4), gives only the mononuclear species
      [Pd(4)(carboxylate)(2)], characterized by X-ray diffraction. This complex forms a
      trimer if one carboxylate is labilized by the addition of strong acid; the
      resulting trinuclear species is readily cleaved by nucleophiles but can include
      weakly basic anions within its cavity.

PMID- 11312739
TI  - Kinetics and mechanism of catalytic decomposition and oxidation of chlorine
      dioxide by the hypochlorite ion.
AB  - The oxidation of ClO(2) by OCl(-)is first order with respect to both reactants in
      the neutral to alkaline pH range: -d[ClO(2)]/dt = 2k(OCl)[ClO(2)][OCl(-)]. The
      rate constant (T = 298 K, mu = 1.0 M NaClO(4)) and activation parameters are
      k(OCl) = 0.91 +/- 0.02 M(-1) s(-1), DeltaH = 66.5 +/- 0.9 kJ/mol, and DeltaS(++)
      = -22.3 +/- 2.9 J/(mol K). In alkaline solution, pH > 9, the primary products of
      the reaction are the chlorite and chlorate ions and consumption of the
      hypochlorite ion is not observed. The hypochlorite ion is consumed in increasing
      amounts, and the production of the chlorite ion ceases when the pH is decreased.
      The stoichiometry is kinetically controlled, and the reactants/products ratios
      are determined by the relative rates of the production and consumption of the
      chlorite ion in the ClO(2)/OCl(-) and HOCl/ClO(2)(-) reactions, respectively.

PMID- 11312740
TI  - Investigating the structural and electronic properties of nitrile hydratase model
      iron(III) complexes using projected unrestricted Hartree-Fock (PUHF)
      calculations.
AB  - Important structural and mechanistic details concerning the non-heme, low-spin
      Fe(III) center in nitrile hydratase (NHase) remain poorly understood. We now
      report projection unrestricted Hartree-Fock (PUHF) calculations on the spin
      preferences of a series of inorganic complexes in which Fe(III) is coordinated by
      a mixed set of N/S ligands. Given that many of these compounds have been prepared
      as models of the NHase metal center, this study has allowed us to evaluate this
      computational approach as a tool for future calculations on the electronic
      structure of the NHase Fe(III) center itself. When used in combination with the
      INDO/S semiempirical model, the PUHF method correctly predicts the experimentally
      observed spin state for 12 of the 13 Fe(III)-containing complexes studied here.
      The one compound for which there is disagreement between our theoretical
      calculations and experimental observation exhibits temperature-dependent spin
      behavior. In this case, the failure of the PUHF-INDO/S approach may be associated
      with differences between the structure of the Fe(III) complex present under the
      conditions used to measure the spin preference and that observed by X-ray
      crystallography. A preliminary analysis of the role of the N/S ligands and
      coordination geometry in defining the Fe(III) spin preferences in these complexes
      has also been undertaken by computing the electronic properties of the lowest
      energy Fe(III) spin states. While any detailed interpretation of our results is
      constrained both by the limited set of well-characterized Fe(III) complexes used
      in this study and by the complicated dependence of Fe(III) spin preference upon
      metal-ligand interactions and coordination geometry, these PUHF-INDO/S
      calculations support the hypothesis that the deprotonated amide nitrogens
      coordinating the metal stabilize the low-spin Fe(III) ground state seen in NHase.
      Strong evidence that the sulfur ligands exclusively define the Fe(III) spin state
      preference by forming metal-ligand bonds with significant covalent character is
      not provided by these computational studies. This might, however, reflect
      limitations in modeling these systems at the INDO/S level of theory.

PMID- 11312741
TI  - The contribution of ligand flexibility to metal center geometry modulated thermal
      cyclization of conjugated pyridine and quinoline metalloenediynes of copper(I)
      and copper(II).
AB  - We report the syntheses, reactivities, and structure evaluations of a series of
      Cu(I) and Cu(II) metalloenediynes of conjugated 1,6-bis(pyridine-3)hex-3-ene-1,5
      diyne (PyED, 7) and 1,6-bis(quinoline-3)hex-3-ene-1,5-diyne (QnED, 8) enediyne
      ligands, as well as their benzoenediyne analogues. Differential scanning
      calorimetry demonstrates that the [Cu(PyED)(2)](NO(3))(2) (11) exhibits a Bergman
      cyclization temperature (156 degrees C) which is dramatically reduced from that
      of the corresponding [Cu(PyED)(2)](PF(6)) (19) analogue (326 degrees C),
      indicating that large differences in the reactivities of these metalloenediynes
      can be accessed by variations in metal oxidation state. The distorted, 4
      coordinate dichloride compound Cu(PyED)(Cl)(2) (15) exhibits a cyclization
      temperature (265 degrees C) between those of 11 and 19, suggesting that variation
      in geometry of the copper center is responsible for the wide range of
      reactivities. Similar results are obtained for the benzoenediyne and quinoline
      analogues. The structures of the Cu(II) systems have also been evaluated by a
      combination of electronic absorption and EPR spectroscopies which reveal
      tetragonal, 6-coordinate structures for the bis(enediyne) complexes, and
      tetrahedrally distorted 4-coordinate Cu(enediyne)Cl(2) species. For the
      bis(quinoline) enediyne derivatives 12 and 14 the larger g-anisotropy (g(
      parallel) = 2.27-2.28; g( perpendicular) = 2.06-2.07) indicates strong oxygen
      coordination from counterion. Molecular mechanics/dynamics calculations reveal
      that the geometries of these metal centers force the alkyne termini to a wide
      range of distances (3.85-4.20 A), thereby accounting for the variability in
      Bergman cyclization temperatures. Overall, the results show that ligand rigidity
      plays a prominent role in the conformational response of the enediyne to metal
      center geometry, which results in enhanced variations in the Bergman cyclization
      temperatures between complexes of different geometries.

PMID- 11312742
TI  - The first metal-rich binary chalcogenides of the lanthanides: Dy(2)Te and
      Gd(2)Te.
AB  - Two new tellurides have been synthesized in Ta with particular attention to the
      use of finely divided Dy (Gd) and a sequence of reactive sintering reactions of
      pressed pellets up to approximately 1060 degrees C. Both phases disproportionate
      to Ln and LnTe at only slightly higher temperatures so that arc-melting
      procedures are relatively unproductive. The two compounds crystallize with a
      Sc(2)Te-type structure. Single-crystal X-ray diffraction results for Dy(2)Te were
      detailed in the orthorhombic space group Pnma (No. 62), Z =12, a = 21.922(4) A, b
      = 4.0650(6) A, and c = 11.428(2) A (Guinier data). There is good evidence for the
      existence of additional metal-rich binary chalcogenides of the heavy lanthanides.
      Extended Huckel calculations were performed within the tight binding
      approximation to aid the understanding of the metal-metal bonding in this system.
      In terms of metal-metal overlap populations, the isotypic Sc(2)Te is more 1D in
      aggregation, while the larger atoms and orbitals and stronger bonding in Dy(2)Te
      make it somewhat more 3D. Electrical resistivity and magnetic susceptibility
      measurements on polycrystalline Dy(2)Te indicate it is metallic and ferromagnetic
      (T(c)= 161.3 K) with an effective moment at higher temperatures close to that of
      ground-state Dy(3+). The connections between heavy lanthanide-rich chalcogenide
      chemistry and that of the early transition metals seem significant.

PMID- 11312743
TI  - Spin distributions, ring conformations, and spiroconjugation in "phosphaverdazyl"
      radicals.
AB  - Reaction of P-dimethylaminophosphonic acid bis(1-methylhydrazide) (6) with
      trimethyl orthobenzoate gave 1,2,5,6-tetrahydro-1,5-dimethyl-6-(N,N
      dimethylamino)-6-phenyl-1,2,4,5,6-tetrazaphosphorine-6-oxide (7), which was
      subsequently oxidized to the corresponding P-diemthylamino-6-phosphaverdazyl (5)
      as a persistent radical. Analysis of the electron paramagnetic resonance spectrum
      of 5 revealed significant spin density on the exocyclic nitrogen but very little
      spin density on the phosphorus, in contrast to the previously reported P-phenyl-6
      phosphaverdazyl (4). Density functional theory calculations on simplified models
      of 4, 5, and related radicals were performed and revealed that spin polarization
      effects and the nature of the substituents on phosphorus have significant effects
      on the structures and spin distributions of these radicals. The spin transfer to
      the dimethylamino group in 5 was revealed to arise from spiroconjugation-type
      overlap between the nitrogen 2p orbital with the verdazyl radical singly occupied
      molecular orbital.

PMID- 11312744
TI  - Electronic and structural variation among copper(II) complexes with substituted
      phenanthrolines.
AB  - A series of copper(II) complexes with substituted phenanthroline ligands has been
      synthesized and characterized electronically and structurally. The compounds that
      have been prepared include the monosubstituted ligand complexes of the general
      formula [Cu(5-R-phen)(2)(CH(3)CN)](BF(4))(2), where R = NO(2), Cl, H, or Me, and
      the disubstituted ligand complex [Cu(5,6-Me(2)-phen)(2)(CH(3)CN)](BF(4))(2). The
      complexes [Cu(5-NO(2)-phen)(2)(CH(3)CN](BF(4))(2) (1), [Cu(5-Cl
      phen)(2)(CH(3)CN)](BF(4))(2) (2), [Cu(o-phen)(2)(CH(3)CN)](BF(4))(2) (3), and
      [Cu(5-Me-phen)(2)(CH(3)CN)](BF(4))(2) (4) each crystallize in the space group
      C2/c with compounds 1, 2, and 4 comprising an isomorphous set. The disubstituted
      complex [Cu(5,6-Me(2)-phen)(2)(CH(3)CN)](BF(4))(2) (5) crystallizes in the space
      group P2(1)/c. Each structure is characterized by a distorted trigonal
      bipyramidal arrangement of ligands around the central copper atom with
      approximate or exact C(2) symmetry. The progression from electron-withdrawing to
      electron-donating substituents on the phenanthroline ligands correlates with less
      accessible reduction potentials for the bis-chelate complexes.

PMID- 11312745
TI  - Novel quaternary lanthanum bismuth sulfides Pb(2)La(x)Bi(8-x)(S(14)),
      Sr(2)La(x)Bi(8-x)S(14), and Cs(2)La(x)Bi(10-x)S(16) with complex structures.
AB  - The compounds Pb(2)La(x)Bi(8-x)S(14) (I), Sr(2)La(x)Bi(8-x)S(14) (II), and
      Cs(2)La(x)Bi(10-x)S(16) (III) were synthesized from the corresponding elements or
      binary sulfides at temperatures above 850 degrees C. Compounds I and II are
      isostructural, forming a new structure type, while the structure of III is
      related to the structure of the mineral kobellite. All compounds crystallize in
      the orthorhombic space group Pnma (No. 62) with a = 21.2592(4) A, b = 4.0418(1)
      A, c = 28.1718(3) A, Z = 4 for I, a = 21.190(1) A, b = 4.0417(2) A, c = 28.285(2)
      A, Z = 4 for II and a = 34.893(4) A, b = 4.0697(4) A, c = 21.508(2) A, Z = 4 for
      III. All compounds exhibit mixed site occupancy between Bi and La. Furthermore, I
      and II exhibit disorder between the divalent atom (Sr or Pb) and/or La and/or Bi.
      The structures of I and II consist of thin walls made of two metal-atom-thick
      NaCl-type blocks running in two opposite directions in the ac plane, forming
      rhombus-shaped tunnels. These tunnels are filled with Bi(2)Te(3)-type fragments.
      In the points where the walls intersect they form Gd(2)S(3)-type fragments. The
      structure of III consists of a complex three-dimensional framework with Cs-filled
      tunnels. All compounds are semiconductors with band gaps around 1.0 eV, and they
      melt around 740-860 degrees C.

PMID- 11312746
TI  - Protonation and deprotonation of TpOs(NHPh)Cl(2): an unusually inert amido
      ligand.
AB  - Protonation of the Os(IV) amido complex TpOs(NHPh)Cl(2) (1) to give the aniline
      complex [TpOs(NH(2)Ph)Cl(2)]OTf (2) requires excess triflic acid (HOTf). Complex
      1 is unreactive with HCl and other moderately strong acids. Consistent with the
      low basicity of 1, the aniline complex 2 is extremely acidic and is deprotonated
      by stoichiometric addition of weak bases such as Cl(-) or H(2)O. No reaction is
      observed between 1 and methyl triflate (CH(3)OTf) at ambient temperatures. Upon
      heating, CH(3)OTf removes the chloride ligands from 1 to give CH(3)Cl and the
      amidobis(triflate) complex TpOs(NHPh)(OTf)(2) (3). Attack at the amido nitrogen
      is not observed. Complex 1 is thus very inert to protonation and electrophilic
      attack at nitrogen. A deprotonated form of 1, TpOs[NPh(MgBr)]Cl(2) (4), is
      generated on reaction of PhMgBr with TpOs(N)Cl(2). Complex 4 is extremely basic
      and will protonate to 1 with weak acids such as CH(3)CN, DMSO, and acetic
      anhydride. Thus, 1 has a low acidity as well as a low basicity; it is both less
      acidic and less basic than aniline. The inertness of 1 is ascribed to partial Os
      N pi bonding and to the oxidizing nature of the Os(IV) center.

PMID- 11312747
TI  - Coordination of rare-earth elements in complexes with monovacant Wells-Dawson
      polyoxoanions.
AB  - The alpha-1 and alpha-2 isomers of the monovacant Wells-Dawson heteropolyoxoanion
      [P(2)W(17)O(61)](10-) are complexants of trivalent rare-earth (RE) ions and serve
      to stabilize otherwise reactive tetravalent lanthanide (Ln) and actinide (An)
      ions in aqueous solution. Aspects of the bonding of Ln ions with alpha-1
      [P(2)W(17)O(61)](10-) and alpha-2-[P(2)W(17)O(61)](10-) were investigated to
      address issues of complex formation and stability. We present structural insights
      about the Ln(III) coordination environment and hydration in two types of
      stoichiometric complexes, [Ln(alpha-1-P(2)W(17)O(61))](7-) and [Ln(alpha-2
      X(2)W(17)O(61))(2)](17-) (for Ln identical with Sm, Eu, Lu; X identical with P,
      As). The crystal and molecular structures of [(H(2)O)(4)Lu(alpha-1
      P(2)W(17)O(61))](7-) (1) and [Lu(alpha-2-P(2)W(17)O(61))(2)](17-) (2) were solved
      and refined through use of single-crystal X-ray diffraction. The crystallographic
      results are supported with corresponding insights from XAFS (X-ray absorption
      fine structure) for a series of nine solid-state complexes as well as from
      optical luminescence spectroscopy of the Eu(III) analogues in aqueous solution.
      All the Ln ions are eight-coordinate with oxygen atoms in a square antiprism
      arrangement. For the 1:1 stoichiometric Ln/alpha-1-[P(2)W(17)O(61)](10-)
      complexes, the Ln ions are bound to four O atoms of the lacunary polyoxometalate
      framework in addition to four O atoms from solvent (water) molecules as
      [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7-). This structure (1) is the first of
      its kind for any metal complex of alpha-1-[P(2)W(17)O(61)](10-), and the data
      indicate that the general stoichiometry [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7
      ) is maintained throughout the lanthanide series. For the 1:2 stoichiometric
      Ln/alpha-2-[X(2)W(17)O(61)](10-) complexes, no water molecules are in the Ln-O(8)
      coordination sphere. The Ln ions are bound to eight O atoms-four from each of two
      heteropolyanions-as [Ln(alpha-2-X(2)W(17)O(61))(2)](17-). The average Ln-O
      interatomic distances decrease across the lanthanide series, consistent with the
      decreasing Ln ionic radius.

PMID- 11312748
TI  - Carbonates, thiocarbonates, and the corresponding monoalkyl derivatives. 1. Their
      preparation and isotropic (13)C NMR chemical shifts.
AB  - Three series of potassium carbonate and thiocarbonate salts were synthesized, and
      the corresponding (13)C isotropic solid-state NMR and the aqueous solution (13)C
      and (1)H NMR data were collected. The series of compounds that were studied
      consists of (1) the parent compounds, i.e., potassium carbonate, K(2)CO(3),
      potassium hydrogen carbonate, KHCO(3), potassium monothiocarbonate, K(2)CO(2)S,
      potassium dithiocarbonate, K(2)COS(2), and potassium trithiocarbonate, K(2)CS(3),
      (2) the oxygen monoalkyl substituted derivatives of the parent compounds (OR
      series), i.e., three potassium O-alkylcarbonates, KO(2)COR, three potassium O
      alkylmonothiocarbonates, KOSCOR, and three potassium O-alkyldithiocarbonates,
      KS(2)COR, all with R = CH(3), CH(2)CH(3), CH(CH(3))(2), and (3) the sulfur
      monoalkyl substituted derivatives of the parent compounds (SR series), i.e., two
      potassium S-alkylmonothiocarbonates, KO(2)CSR; two potassium S
      alkyldithiocarbonates, KOSCSR, and two potassium S-alkyltrithiocarbonates,
      KS(2)CSR, all with R = CH(3) or CH(2)CH(3). The preparation and proper
      characterization of KO(2)CSR and KOSCSR with R = CH(3) and CH(2)CH(3) along with
      new IR and X-ray powder diffraction data for several other compounds in the
      series are reported for the first time in this study. Solution NMR data for
      KO(2)CSR (R = CH(3), CH(2)CH(3)) and KOSCSR (R = CH(3)) and solid-state NMR data
      for K(2)CO(2)S and K(2)COS(2) could not be obtained because they are unstable
      under the corresponding measurement conditions. The isotropic chemical shift
      values of the central carbon atoms obtained from solid-state MAS (magic angle
      spinning) NMR experiments deviate at most by 3 ppm from the corresponding
      solution values. Two major trends in the (13)C chemical shift values of the
      central carbon atoms were found. First, if an oxygen atom in a parent compound or
      in an alkyl-substituted derivative is replaced by a sulfur atom, a significantly
      higher chemical shift value is observed. This trend is discussed in terms of the
      paramagnetic contribution to the chemical shielding constant. Second, the size of
      the alkyl group in the monoalkyl derivatives has a very small effect on the
      chemical shift values of the central carbon atoms. This observation is explained
      using the concept of varying inductive effects produced by alkyl groups. The
      trends observed for the (13)C and (1)H chemical shift values of the alkyl groups
      follow common concepts on the structure dependency of chemical shifts.

PMID- 11312749
TI  - Carbonates, thiocarbonates, and the corresponding monoalkyl derivatives. 2. X-ray
      crystal structure of potassium methyltrithiocarbonate (KS(2)CSCH(3)).
AB  - This study presents the first crystal structure determination of a potassium S
      alkylthiocarbonate, the title compound potassium methyltrithiocarbonate
      (KS(2)CSCH(3)) Single crystals of KS(2)CSCH(3) were obtained by the slow
      introduction of methylene chloride into a saturated solution of KS(2)CSCH(3) in a
      1:1 mixture of methylene chloride and tetrahydrofuran at 0 degrees C in a dry
      N(2) atmosphere. The compound crystallizes in the monoclinic space group P2(1)/c
      containing Z = 4 K(+) cations and S(2)CSCH(3-) anions per unit cell. The unit
      cell dimensions are a = 7.6639(3) A, b = 6.5804(2) A, c = 12.8426(5) A, and beta
      = 91.565(2) degrees. The isomorphism to the structurally closely related
      compounds KO(2)COCH(3), KOSCOCH(3), and KS(2)COCH(3) is examined.

PMID- 11312750
TI  - Solvent dependence of the structure and magnetic ordering of ferrimagnetic
      manganese(III) meso-tetraphenylporphyrin tetracyanoethenide, [MnTPP]+[TCNE]*-.
AB  - Tetraphenylporphinatomanganate(III) tetracyanoethenide, [MnTPP][TCNE], is the
      prototype of a growing family of linear chain (1-D) coordination polymers that
      magnetically order as ferrimagnets. [MnTPP][TCNE].xS [S = PhMe (x = 2), 1,2
      C(6)H(4)Me(2) (x = 1), 1,2-C(6)H(4)Cl(2) (x = 3), 1,2,4-C(6)H(3)Cl(3) (x = 2),
      and 1,3-C(6)H(4)Cl(2) (x = 2)] have been prepared and structurally and
      magnetically characterized. All form 1-D chain structures with intrachain Mn.Mn
      separations ranging from 9.202 to 10.218 A. The 173 K crystal structure of
      [MnTPP][TCNE].2PhMe has been rerefined, revealing that the [TCNE](*)(-) is 2-fold
      disordered and coordinated to Mn(III) by a pair of trans cyano nitrogen atoms to
      form parallel one-dimensional chains. The two orientations of [TCNE](*)(-) are
      related by a 180 degrees rotation about the diagonal axis joining the trans
      nitrogen atoms bound to Mn(III). The major form has an occupancy of 83.3(4)% with
      a Mn-N(TCNE) distance of 2.328(3) A and a MnNC angle of 146.8(8) degrees. The
      minor form, with 16.7(4)% occupancy, has a Mn-N(TCNE) distance of 2.176(15) A and
      a MnNC angle of 152.3(39) degrees. Lattice packing and molecular bonding imply
      static as opposed to dynamic disorder. The magnetic properties depend on the type
      and quantity of the solvent present in the structure. Desolvation via heating in
      n-octane (127 degrees C), n-dodecane (216 degrees C), and/or vacuum thermolysis
      (175 degrees C) leads to numerous different desolvated materials with differing
      magnetic properties. At higher temperatures the magnetic susceptibility can be
      fit by the Curie-Weiss expression, chi varies with (T - theta)(-1), with theta =
      44, 52, 72, 55, and 77 K for the toluene, 1,2-xylene, 1,2-dichlorobenzene, 1,3
      dichlorobenzene, and 1,2,4-trichlorobenzene solvates, respectively. The T(c)'s
      were taken as the maximum in 10 Hz chi'(T) and are 7.8, 9.2, 11.3, 10.8, and 8.2
      K for the PhMe, 1,2-xylene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, and 1,2,4
      trichlorobenzene solvates, respectively. Upon desolvation the T(c)'s increase for
      the PhMe, 1,2-xylene, 1,2,4-trichlorobenzene solvates and decrease for the 1,2-
      and 1,3-dichlorobenezene solvates. The compounds show one-dimensional
      ferrimagnetic exchange behavior at high temperatures with intrachain exchange of
      J/k(b) = -63, -99, -234, -100, and -200 K for toluene, 1,2-xylene, 1,2
      dichlorobenzene, 1,3-dichlorobenzene, and 1,2,4-trichlorobenzene solvates,
      respectively, as determined from fits to the Seiden expression, which models
      isolated 1-D interactions among alternating S = 2 classical and S = (1)/(2)
      quantum spins. For variation in the temperature at which the peak occurs per
      decade of frequency, phi, (DeltaT(f)/T(f))/Delta(log omega) is 0.167, 0.168,
      0.066, 0.171, and 0.024 for toluene, 1,2-xylene, 1,2-dichlorobenzene, 1,3
      dichlorobenzene, and 1,2,4-trichlorobenzene, respectively, typical of spin glass
      behavior. Since [TCNE](*)(-) is only disordered for the PhMe solvate and all five
      solvates exhibit spin glass behavior, the spin glass behavior cannot be
      attributed to this disorder.

PMID- 11312751
TI  - Tetracyanomanganate(II) and its salts of divalent first-row transition metal
      ions.
AB  - The first known paramagnetic, tetrahedral cyanide complex, [Mn(II)(CN)(4)](2)(-),
      is formed by the photoinduced decomposition of [Mn(IV)(CN)(6)](2)(-) in
      nonaqueous solutions or by thermal decomposition in the solid state. In
      acetonitrile or dichloromethane, photoexcitation into the ligand-to-metal charge
      transfer band (lambda(max) = 25 700 cm(-1), epsilon = 3700 cm(-1) M(-1)) causes
      the homolytic cleavage of cyanide radicals and reduction of Mn(IV). Free cyanide
      in dichloromethane leads to the isolation of polycyanide oligomers such as
      [C(12)N(12)](2)(-) and [C(4)N(4)](-), which was crystallographically
      characterized as the PPN(+) salt C(40)H(30)N(5)P(2): monoclinic space group =
      I2/a, a = 18.6314(2) A, b = 9.1926(1) A, c = 20.8006(1), beta =106.176(2)
      degrees, Z = 4]. In the solid state Mn(IV)-CN bond homolysis is thermally
      activated above 122 degrees C, according to differential scanning calorimetry
      measurements, leading to the reductive elimination of cyanogen. The
      [Mn(II)(CN)(4)](2-) ion has a dynamic solution behavior, as evidenced by its
      concentration-dependent electronic and electron paramagnetic spectra, that can be
      attributed to aggregation of the coordinatively and electronically unsaturated
      (four-coordinate, 13-electron) metal center. Due to dynamics and lability of
      [Mn(II)(CN)(4)](2-) in solution, its reaction with divalent first-row transition
      metal cations leads to the formation of lattice compounds with both tetrahedral
      and square planar local coordination geometries of the metal ions and multiple
      structural and cyano-linkage isomers. alpha-Mn(II)[Mn(II)(CN)(4)] has an
      interpenetrating sphalerite- or diamond-like network structure with a unit cell
      parameter of a = 6.123 A (P43m space group) while a beta-phase of this material
      has a noninterpenetrating disordered lattice containing tetrahedral
      [Mn(II)(CN)(4)](2-). Linkage isomerization or cyanide abstraction during
      formation results in alpha-Mn(II)[Co(II)(CN)(4)] and Mn(II)[Ni(II)(CN)(4)]
      lattice compounds, both containing square planar tetracyanometalate centers.
      alpha-Mn(II)[Co(II)(CN)(4)] is irreversibly transformed to its beta-phase in the
      solid state by heating to 135 degrees C, which causes a geometric isomerization
      of [Co(II)(CN)(4)](2)(-) from square planar (nu(CN) = 2114 cm(-1), S = (1)/(2))
      to tetrahedral (nu(CN) = 2158 cm(-1), S = (3)/(2)) as evidenced by infrared and
      magnetic susceptibility measurements. Mn(II)[Ni(II)(CN)(4)] is the only phase
      formed with Ni(II) due to the high thermodynamic stability of square planar
      [Ni(II)(CN)(4)](2)(-).

PMID- 11312752
TI  - Preparation and X-ray structures of Cu(I), Ni(II), and Pd(II) (N,S) complexes of
      the monoanion [(tBuN)(S)P(mu-N(t)Bu)2P(S)(NH(t)Bu)]- and a Pt(II) (S,S') complex
      of the dianion [((t)BuN)(S)P(mu-N(t)Bu)2P(S)(N(t)Bu)]2-.
AB  - The metathetical reactions of the lithium derivative of the monoanion
      [((t)BuN)(S)P(mu-N(t)Bu)(2)P(S)(NH(t)Bu)](-) (L) with CuCl/PPh(3),
      NiCl(2)(PEt(3))(2), PdCl(2)L'(2) (L' = PhCN, PPh(3)), and PtCl(2)(PEt(3))(2)
      produced the complexes (PPh(3))CuL (5), NiL(2) (6), PdCl(L)(PPh(3)) (7), PdL(2)
      (8), and Pt(PEt(3))(2)[((t)BuN)(S)P(mu-N(t)Bu)(2)P(S)(N(t)Bu)] (9). The X-ray
      structures of 5, 6, and 8 reveal a N,S-coordination for the chelating monoanion L
      with the metal centers in trigonal planar, tetrahedral, and square planar
      environments, respectively. By contrast, the dianionic ligand in the square
      planar Pt(II) complex 9 is S,S'-chelated to the metal center. (31)P NMR spectra
      readily distinguish between the N,S and S,S' bonding modes, and, on that basis,
      N,S chelation is inferred for the Pd(II) complex 7. Crystal data: 5, monoclinic,
      P2(1)/c, a = 19.175(4) A, b = 20.331(4) A, c = 10.017(6) A, beta = 91.79(3)
      degrees, V = 3903(2) A(3), and Z = 4; 6, orthorhombic, Pbcn, a = 14.298(5) A, b =
      15.333(5) A, c = 24.378(5) A, beta = 90.000(5) degrees, V = 5344(3) A(3), and Z =
      4; 8, monoclinic, P2(1)/n, a = 13.975(3) A, b = 14.283(3) A, c = 15.255(4) A,
      beta = 116.565(18) degrees, V = 2723.5(11) A(3), and Z = 2; 9, monoclinic,
      P2(1)/n, a = 12.479(6) A, b = 21.782(7) A, c = 17.048(5) A, beta = 100.30(3)
      degrees, V = 4559(3) A(3), and Z = 4.

PMID- 11312753
TI  - Magnetic polyoxometalates: anisotropic antiferro- and ferromagnetic exchange
      interactions in the pentameric cobalt(II) cluster.
AB  - The ground-state properties of the pentameric Co(II) cluster
      [Co(3)W(D(2)O)(2)(CoW(9)O(34))(2)](12-) were investigated by combining magnetic
      susceptibility and low-temperature magnetization measurements with a detailed
      inelastic neutron scattering (INS) study on a fully deuterated polycrystalline
      sample of Na(12)[Co(3)W(D(2)O)(2)(CoW(9)O(34))(2)].46D(2)O. The encapsulated
      magnetic Co(5) unit consists of three octahedral and two tetrahedral oxo
      coordinated Co(II) ions. Thus, two different types of exchange interactions are
      present within this cluster: a ferromagnetic interaction between the octahedral
      Co(II) ions and an antiferromagnetic interaction between the octahedral and the
      tetrahedral Co(II) ions. As a result of the single-ion anisotropy of the
      octahedral Co(II) ions, the appropriate exchange Hamiltonian to describe the
      ground-state properties of the Co(5) spin cluster is anisotropic and is expressed
      as H = -2 summation operator(i= x,y,z)J(1)(i)[S(1)(i)S(2)(i) + S(2)(i)S(3)(i)] +
      J(2)(i)[S(1)(i)S(5)(i) + S(2)(i)S(5)(i) + S(2)(i)S(6)(i) + S(3)(i)S(6)(i)], where
      J(1)(i) are the components of the exchange interaction between the octahedral
      Co(II) ions and J(2)(i) are the components of the exchange interaction between
      the octahedral and tetrahedral Co(II) ions (see Figure 1d). The study of the
      exchange interactions in the two structurally related polyoxoanions
      [Co(4)(H(2)O)(2)(PW(9)O(34))(2)](10)(-) and
      [Co(3)W(H(2)O)(2)(ZnW(9)O(34))(2)](12)(-) allowed an independent determination of
      the ferromagnetic exchange parameters J(1)(x) = 0.70 meV, J(1)(y) = 0.43 meV, and
      J(1)(z) = 1.51 meV (set a) and J(1)(x) = 1.16 meV, J(1)(y) = 1.16 meV and J(1)(z)
      = 1.73 meV (set b), respectively. Our analysis proved to be much more sensitive
      to the size and anisotropy of the antiferromagnetic exchange interaction J(2). We
      demonstrate that this exchange interaction exhibits a rhombic anisotropy with
      exchange parameters J(2)(x) = -1.24 meV, J(2)(y) = -0.53 meV, and J(2)(z) = -1.44
      meV (set a) or J(1)(x) = -1.19 meV, J(1)(y) = -0.53 meV, and J(1)(z) = -1.44 meV
      (set b). The two parameter sets reproduce in a satisfactory manner the
      susceptibility, magnetization, and INS properties of the title compound.

PMID- 11312754
TI  - Syntheses and structural characterization of dinuclear and tetranuclear iron(III)
      complexes with dinucleating ligands and their reactions with hydrogen peroxide.
AB  - The iron(III) complexes [Fe(2)(HPTB)(mu-OH)(NO(3))(2)](NO(3))(2).CH(3)OH.2H(2)O
      (1), [Fe(2)(HPTB)(mu-OCH(3))(NO(3))(2)](NO(3))(2).4.5CH(3)OH (2), [Fe(2)(HPTB)(mu
      OH)(OBz)(2)](ClO(4))(2).4.5H(2)O (3), [Fe(2)(N-EtOH-HPTB)(mu
      OH)(NO(3))(2)](ClO(4))(NO(3)).3CH(3)OH.1.5H(2)O (4), [Fe(2)(5,6-Me(2)-HPTB)(mu
      OH)(NO(3))(2)](ClO(4))(NO(3)).3.5CH(3)OH.C(2)H(5)OC(2)H(5).0.5H(2)O (5), and
      [Fe(4)(HPTB)(2)(mu-F)(2)(OH)(4)](ClO(4))(4).CH(3)CN.C(2)H(5)OC(2)H(5).H(2)O (6)
      were synthesized (HPTB = N,N,N',N'-tetrakis(2-benzimidazolylmethyl)-2-hydroxo-1,3
      diaminopropane, N-EtOH-HPTB = N,N,N',N'-tetrakis(N' '-(2-hydroxoethyl)-2
      benzimidazolylmethyl)-2-hydroxo-1,3-diaminopropane, 5,6-Me(2)-HPTB = N,N,N',N'
      tetrakis(5,6-dimethyl-2-benzimidazolylmethyl)-2-hydroxo-1,3-diaminopropane). The
      molecular structures of 2-6 were established by single-crystal X-ray
      crystallography. Iron(II) complexes with ligands similar to the dinucleating
      ligands described herein have been used previously as model compounds for the
      dioxygen uptake at the active sites of non-heme iron enzymes. The same metastable
      (mu-peroxo)diiron(III) adducts were observed during these studies. They can be
      prepared by adding hydrogen peroxide to the iron(III) compounds 1-6. Using
      stopped-flow techniques these reactions were kinetically investigated in
      different solvents and a mechanism was postulated.

PMID- 11312755
TI  - Synthetic and structural studies of the coordination behavior of 2
      pyridylbis(diphenylphosphino)methane.
AB  - The coordination chemistry of the potentially semilabile tridentate ligand 2
      pyridylbis(diphenylphosphino)methane (NPP) has been investigated. Bidentate (N,
      P) coordination occurs in CoCl(2)(NPP) (1) and [CdX(mu-X)(NPP)](2) (X = Cl (2);
      OAc (3)), prepared from the corresponding metal salts, in fac-Re(CO)(3)Br(NPP)
      (4) and in Fe(CO)(2)(MA)(NPP) (6). The last is one of three products from the
      reaction of Fe(CO)(4)(MA) (MA = maleic anhydride) with NPP, the other two being
      Fe(CO)(3)(NPP) (7; P, P coordinated) and the unusual cyclic ylid Ph2PC(2
      C5H4N)PPh2C(CH2CO2H)C(=O)(5). The ligand shows tridentate coordination in
      Cr(CO)(3)(NPP) (9), RuCl(2)(PPh(3))(NPP) (10), and possibly in PtCl(2)(NPP) (8).
      Carbon monoxide displaces one phosphorus arm of the ligand in 10. Anhydrous
      NiCl(2) and NPP react in the presence of methanol to give
      NiCl(2)(P(OMe)Ph(2))(Ph(2)PCH(2)py) (12) in which the NPP ligand has been
      cleaved. This in turn reacts with O(2) to form trans-NiCl(2)(Ph(2)P(O)CH(2)py)(2)
      (13). The methine proton of NPP is transferred to the metal on reaction with
      Pt(C(2)H(4))(PPh(3))(2) and [Ir(COD)(NPP)]BF(4) to form the hydride complexes
      Pt(H)(PPh(3))(NPP-H) (14) and [Ir(H)(NPP)(NPP-H)]BF(4) (15). In 15 the intact NPP
      ligand is tridentate. The structures of 1 - 7 and 12 - 15 have been determined.

PMID- 11312756
TI  - Deprotonation of ferraborane clusters and their relative acidities.

PMID- 11312757
TI  - The many guises of lithium chloride: crystal structure of the single-strand
      polymer [LiCl.2MeCn](infinity).

PMID- 11312758
TI  - Bi(2)TeO(5): synthesis, structure, and powder second harmonic generation
      properties.

PMID- 11312759
TI  - Preparative isolation of anthocyanins by high-speed countercurrent chromatography
      and application of the color activity concept to red wine.
AB  - Red pigments were isolated from wine and grape-skin extracts using preparative
      high-speed countercurrent chromatography (HSCCC) and identified by NMR and MS
      techniques. Four solvent systems were developed in order to separate anthocyanins
      with different polarities. Malvidin-3-glucoside was the major component present
      in young red wines, and up to 500 mg of pure malvidin-3-glucoside could be
      obtained from a single bottle of a red wine. Other isolated pigments were the
      malvidin- and peonidin-3,5-diglucosides, as well as acetyl-, coumaroyl-, and
      caffeoyl-derivatives of anthocyanins. Furthermore, condensed red wine pigments
      formed from malvidin-3-glucoside (vitisin A and acetylvitisin A) were isolated on
      a preparative scale. Isolated compounds were used as standards for quantification
      of anthocyanins in a range of red wines. The "color activity concept" was applied
      to red wine, and visual detection thresholds were determined for some of the
      isolated anthocyanins. Mono-glucosides were found to exhibit lower visual
      detection thresholds than di-glucosides and acylated anthocyanins.

PMID- 11312760
TI  - Gas chromatographic-mass spectrometric method for the analysis of dimethomorph
      fungicide in dried hops.
AB  - An analytical method for the determination of dimethomorph [(E,Z)-4-[3-(4
      chlorophenyl)-3-(3,4-dimethoxyphenyl)acryloyl]morpholine] residues in dried hops
      was developed utilizing liquid-liquid partitioning, automated gel permeation
      chromatography (GPC), Florisil and aminopropyl solid phase extraction (SPE)
      column cleanups, and gas chromatography (GC) with mass selective detection (MSD).
      Method validation recoveries from dried hops ranged from 79 to 103% over four
      levels of fortification (0.1, 1.0, 5.0, and 20 ppm). Control and dimethomorph
      treated hop samples collected from three field sites had residue levels of <0.10
      and 4.06-17.32 ppm, respectively. The method was validated to the limit of
      quantitation at 0.10 ppm. The limit of detection for this method was 0.045 ppm.

PMID- 11312761
TI  - Determination of flavonoids in plant material by HPLC with diode-array and
      electro-array detections.
AB  - A high-performance liquid chromatographic (HPLC) method with in-line connected
      diode-array (DAD) and electro-array (EC) detection to identify and quantify 17
      flavonoids in plant-derived foods is described. Catechins were extracted from the
      samples using ethyl acetate, and quantification of these compounds was performed
      with the EC detector. Other flavonoids were quantified with DAD after acid
      hydrolysis. The methods developed were effective for the determination of
      catechins and other flavonoids in plant-derived foods. Responses of the detection
      systems were linear within the range evaluated, 20-200 ng/injection (DAD) and 20
      100 ng/injection (EC), with correlation coefficients exceeding 0.999. Coefficient
      of variation was under 10.5%, and recoveries of flavonoids ranged from 70 to
      124%. Purity of the flavonoid peaks was confirmed by combining the spectral and
      voltammetric data.

PMID- 11312762
TI  - Development of a dual-label time-resolved fluorometric immunoassay for the
      simultaneous detection of two recombinant proteins in potato.
AB  - Immunological methods such as ELISA have been traditionally employed to quantify
      protein levels in plants improved through modern biotechnology. Combined trait
      products (i.e., plants producing multiple recombinant proteins) created by
      introducing multiple genetic traits by transformation or traditional breeding
      methods have prompted the need for the development of analytical assay
      technologies capable of detecting and quantifying multiple proteins in a single
      assay. The development of a two-site, sandwich, dual-label, time-resolved
      fluorometry-based immunoassay (TRFIA) capable of simultaneously quantitating two
      recombinant proteins (CP4 EPSPS and Cry3A) in plant sample extracts of
      genetically improved potato cultivars is reported here. The performance
      characteristics of TRFIA were similar to or exceeded those of current ELISA
      methods used to detect and quantitate these proteins. TRFIA is a practical and
      reliable assay for the quantitation of proteins in genetically improved potato
      plants and offers an alternative approach to conventional ELISA methods with the
      added benefit of multiple analyte detection.

PMID- 11312763
TI  - Comparison among soil Series and extraction methods for the analysis of
      trifluralin.
AB  - Accurate analytical procedures are needed to improve understanding of the fate
      and transport of trifluralin, a chemical widely used as a herbicide. Analytical
      determination of trifluralin is challenging due to its hydrophobic, yet volatile,
      character and its tendency to degrade into numerous metabolites. In this
      research, efficient analytical methods for fortified and field-incurred soils
      were developed for simultaneous quantitation of trifluralin, I [2,6-dinitro-N,N
      dipropyl-4-(trifluoromethyl)benzenamine, CAS Registry No. 1582-09-8; CAS Registry
      No. have been provided by the author], a trifluralin metabolite, II [2,6-dinitro
      N-propyl-4-(trifluoromethyl)benzenamine, CAS Registry No. 2077-99-8], and a
      related trifluoromethyldinitroaniline isomer of trifluralin, III [2,4-dinitro-N,N
      dipropyl-6-(trifluoromethyl)benzenamine, CAS Registry No. 23106-20-9].
      Extractions of trifluralin (0.5 and 2.5 microg/g) from silt loam, sandy loam, and
      silty clay soils were compared. A method was developed for the supercritical
      fluid extraction of trifluralin from soil using modified supercritical carbon
      dioxide, and the effects of cosolvent, pressure, and flow rate on recovery were
      evaluated. Supercritical fluid extraction was compared to liquid vortex
      extraction and automated Soxhlet (soxtec) extraction. Solid-phase extraction was
      examined for purifying soil extracts. Protocols were developed for analysis of
      extracts by gas and/or liquid chromatography. Immunoassay was investigated but
      proven to be impractical for this analysis. Soil properties and extraction
      methods were observed to affect the level of coextracted background
      interferences. Trifluralin exhibited concentration-dependent recovery regardless
      of soil series or extraction method.

PMID- 11312764
TI  - Comparison of enzyme-linked immunosorbent assay and gas chromatography procedures
      for the detection of cyanazine and metolachlor in surface water samples.
AB  - Enzyme-linked immunosorbent assay (ELISA) data from surface water reconnaissance
      were compared to data from samples analyzed by gas chromatography for the
      pesticide residues cyanazine (2-[[4-chloro-6-(ethylamino)-1,3,5-triazin-2
      yl]amino]-2-methylpropanenitrile) and metolachlor (2-chloro-N-(2-ethyl-6
      methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide). When ELISA analyses were
      duplicated, cyanazine and metolachlor detection was found to have highly
      reproducible results; adjusted R2s were 0.97 and 0.94, respectively. When ELISA
      results for cyanazine were regressed against gas chromatography results, the
      models effectively predicted cyanazine concentrations from ELISA analyses
      (adjusted R2s ranging from 0.76 to 0.81). The intercepts and slopes for these
      models were not different from 0 and 1, respectively. This indicates that
      cyanazine analysis by ELISA is expected to give the same results as analysis by
      gas chromatography. However, regressing ELISA analyses for metolachlor against
      gas chromatography data provided more variable results (adjusted R2s ranged from
      0.67 to 0.94). Regression models for metolachlor analyses had two of three
      intercepts that were not different from 0. Slopes for all metolachlor regression
      models were significantly different from 1. This indicates that as metolachlor
      concentrations increase, ELISA will over- or under-estimate metolachlor
      concentration, depending on the method of comparison. ELISA can be effectively
      used to detect cyanazine and metolachlor in surface water samples. However, when
      detections of metolachlor have significant consequences or implications it may be
      necessary to use other analytical methods.

PMID- 11312765
TI  - MALDI-TOF MS analysis of isoflavones in soy products.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is a new technique having a number of advantages for food
      analysis. This study is the first to demonstrate the use of MALDI-TOF MS to
      identify isoflavones in soy samples. 2',4',6'-Trihydroxyacetophenone (THAP) and
      2,5-dihydroxybenzoic acid (DHB) were both good matrices for isoflavones, but DHB
      was chosen as the best because it worked well for sample extracts, with good spot
      to-spot repeatability. Isoflavones were predominantly ionized in a protonated
      form with a very small amount of sodium or potassium adduct ions. Fragmentation
      occurred only through loss of glycosidic residues. Daidzin showed more than twice
      the response of genistin using MALDI-TOF MS. A simple solid phase extraction of
      isoflavones from soy samples was developed for MALDI-TOF MS analysis. MALDI-TOF
      MS can provide an isoflavone profile in 2 min and serves as a powerful tool to
      identify and study processing changes of isoflavones in soy products.

PMID- 11312766
TI  - Genetic fingerprinting of grape plant (Vitis vinifera) using random amplified
      polymorphic DNA (RAPD) analysis and dynamic size-sieving capillary
      electrophoresis.
AB  - Dynamic size-sieving capillary electrophoresis with laser-induced fluorescence
      detection (DSCE-LIF) was combined with random amplified polymorphic DNA (RAPD)
      analysis to demonstrate the feasibility of the genetic analysis of grape plant
      varieties and clones within a variety. Parameters of the genomic DNA extraction
      process, as well as those of the RAPD analysis, were optimized specifically for
      this application. Polymorphic DNA fragments were generated for four different
      grape plant varieties including Cabernet Franc, Cabernet Sauvignon, Merlot, and
      Chardonnay. Relative to slab gel electrophoresis (SGE) with ethidium bromide
      staining, DSCE-LIF provided superior separation efficiency and detection limits
      in the analysis of DNA polymorphic bands. Optimal DSCE-LIF analyses were achieved
      using a 10-fold RAPD sample dilution, hydrodynamic sample injection, and 100
      ng/mL of YO-PRO-1 DNA intercalator in the dynamic size-sieving buffer solution.
      In addition, the reproducibility of both the DSCE-LIF and RAPD analyses were
      demonstrated.

PMID- 11312767
TI  - Development of a class-selective enzyme-linked immunosorbent assay for
      mercapturic acids in human urine.
AB  - Epidemiological and toxicological studies often require the analysis of large
      numbers of samples for biological markers of exposure. The goal of this work was
      to develop a class-selective ELISA to detect groups of structurally closely
      related mercapturic acids with small nonpolar S-substituents. An assay was
      developed with strong recognition for mercapturates including S-benzylmercapturic
      acid (IC50 = 0.018 micromol/L), S-n-hexylmercapturic acid (IC50 = 0.021
      micromol/L), S-phenylmercapturic acid (IC50 = 0.024 micromol/L), and S
      cyclohexylmethylmercapturic acid (IC50 = 0.042 micromol/L). The same assay also
      showed weaker recognition for S-(1-hydroxynaphthal-2-yl)mercapturic acid and S
      allylmercapturic acid (IC50 = 1.1 and 1.7 micromol/L, respectively). Subtle
      modifications to the hapten linker structure of the coating antigen proved to
      have a strong impact on the selectivity and the specificity of the assay. A
      slightly modified assay showed high recognition for S-benzylmercapturic acid
      (IC50 = 0.018 micromol/L) and weaker recognition for seven other mercapturic
      acids (IC50 = 0.021-10 micromol/L). Strong positive assay responses were detected
      in 12 urine samples obtained from persons with no known occupational exposure to
      exogenous electrophilic xenobiotics. Solid phase extraction and cross-reactivity
      indicated that the presumptive immunoreactive materials were similar in size and
      polarity to S-benzylmercapturic acid. The assay was more selective to mercapturic
      acids than the spectrophotometric thioether assay.

PMID- 11312768
TI  - Compositional analysis of tubers from insect and virus resistant potato plants.
AB  - Genetically modified potato plants that are resistant to the Colorado potato
      beetle, plus either the potato leaf roll virus or potato virus Y, have recently
      been commercialized. As part of the safety assessment for plants produced by
      modern biotechnology, the composition of the food/feed must be compared to that
      of the food/feed produced by an equivalent plant variety from a conventional
      source. The composition of important nutritional and antinutritional factors in
      tubers produced by virus- and insect-resistant potato plants were compared to
      tubers produced by conventional potato plants. Key nutritional, quality, and
      antinutritional components measured were total solids, vitamin C, dextrose,
      sucrose, soluble protein, and glycoalkaloids. Proximate analyses included fat,
      ash, calories, total protein, and crude fiber. Minor nutrients measured were
      vitamin B6, niacin, copper, magnesium, potassium, and amino acids. The results
      from these analyses confirm that tubers produced by insect- and virus-protected
      varieties are substantially equivalent to tubers produced by conventional potato
      varieties.

PMID- 11312769
TI  - Analysis and stability of carotenoids in the flowers of daylily (Hemerocallis
      disticha) as affected by various treatments.
AB  - The analysis and stability of carotenoids in the flowers of daylily (Hemerocallis
      disticha) as affected by soaking and drying treatments were studied. The various
      carotenoids in the flowers of daylily were analyzed using a reversed-phase C(30)
      HPLC column and a mobile phase of methanol/methylene chloride/2-propanol
      (89:1:10, v/v/v) with methanol/methylene chloride (45:55, v/v) as sample solvent.
      Twenty-one pigments were resolved, of which 14 carotenoids were identified,
      including neoxanthin, violaxanthin, violeoxanthin, lutein-5,6-epoxide, lutein,
      zeaxanthin, beta-cryptoxanthin, all-trans-beta-carotene, and their cis isomers,
      based on spectral characteristics and Q ratios. Prior to hot-air-drying (50
      degrees C) or freeze-drying, some of the daylily flowers were subjected to
      soaking in a sodium sulfite solution (1%) for 4 h. Under either the hot-air- or
      the freeze-drying treatment, the amounts of most carotenoids were higher in the
      soaked daylily flowers than in those that were not soaked. With hot-air-drying,
      the amount of cis carotenoids showed a higher yield in soaked samples than in
      nonsoaked samples. However, with freeze-drying, only a minor change of each
      carotenoid was observed for both soaked and nonsoaked samples. Also, air-drying
      resulted in a higher loss of carotenoids than freeze-drying.

PMID- 11312770
TI  - Stability study of a sulfadimidine-containing medicated premix and its mixture
      with farm feed.
AB  - The objective of this paper was to study the stability of a medicated premix and
      a medicated farm feed containing sulfadimidine as the active ingredient. The
      medicated premix is supplied as powdered form and administered orally after
      mixing with animal feed. The sulfadimidine analytical method described in United
      States Pharmacopoeia 23 cannot be used to carry out the stability study because
      of its lack of specificity for different degradation products. Therefore, a high
      performance liquid chromatography method was developed to assay sulfadimidine.
      This method was optimized and validated for the stability study. According to
      International Committee Harmonization (ICH) guidelines, the samples were stored
      under long-term testing and accelerated conditions for the stability study of the
      premix and the medicated farm feed. Sulfadimidine degradation was not detected in
      either form under any of the conditions studied.

PMID- 11312771
TI  - Physicochemical, nutritional, and microstructural characteristics of chickpeas
      (Cicer arietinum L.) and common beans (Phaseolus vulgaris L.) following microwave
      cooking.
AB  - Microwave cooking of legumes such as chickpeas and common beans was evaluated by
      assessing the cooking quality (cooking time, firmness, cooking losses, and water
      uptake) and the physicochemical, nutritional, and microstructural modifications
      in starch and nonstarch polysaccharides. Compared to conventional cooking,
      microwave cooking with sealed vessels enabled a drastic reduction in cooking
      time, from 110 to 11 min for chickpeas and from 55 to 9 min for common beans. The
      solid losses, released in the cooking water, were significantly less after
      microwave cooking than after conventional cooking (6.5 vs 10.6 g/100 g of dry
      seed in chickpeas and 4.5 vs 7.5 g/100 g of dry seed in common beans). Both
      cooking procedures produced a redistribution of the insoluble nonstarch
      polysaccharides to soluble fraction, although the total nonstarch polysaccharides
      were not affected. Increases in in vitro starch digestibility were similar after
      both cooking processes, since the level of resistant starch decreased from 27.2
      and 32.5% of total starch in raw chickpeas and beans, respectively, to about 10%
      in cooked samples and the level of rapidly digestible starch increased from 35.6
      and 27.5% to about 80%. SEM studies showed that the cotyledons maintained a
      regular structure although most of the cell wall was broken down and shattered by
      both cooking procedures. In addition, the ultrastructural modifications in the
      cotyledon's parenchima and cells are consistent with the chemical modifications
      in NSP and the increase in starch digestibility after cooking.

PMID- 11312772
TI  - Phenolic composition of litchi fruit pericarp.
AB  - Litchi (Litchi chinensis, Sapindaceae) is a nonclimacteric subtropical fruit
      that, once harvested, loses its red pericarp color because of browning reactions
      probably involving polyphenols. Low-pressure chromatography, high-pressure liquid
      chromatography, UV-visible spectral analysis, mass spectrometry, and nuclear
      magnetic resonance studies have allowed the determination and quantification of
      the polyphenolic composition of litchi pericarp. Litchi skins contain significant
      amounts of polyphenolic compounds. The principal characteristic of the litchi
      skin polyphenolic compounds is their ortho-diphenolic structure, which gives them
      high oxidability. Four major pigments were formally identified as cyanidin 3
      rutinoside, cyanidin glucoside, quercetin 3-rutinoside (rutin), and quercetin
      glucoside. The tannin content was characterized after the depolymerization
      thiolysis reaction. Tannins (polymeric proanthocyanidins) are mainly constituted
      with epicatechin units linked by A- and B-type bonds. The different phenolic
      compounds of litchi cv. Kwai Mi were quantified by HPLC. Condensed tannins were
      the most abundant (4 mg x g(-1) of fresh skin), followed by epicatechin and
      procyanidin A2 (1.7 and 0.7 mg x g(-1) of fresh pericarp, respectively). The
      amount of anthocyanins was found to be comparable to that of flavonols, with a
      value of approximately 0.4 mg x g(-1) of fresh pericarp.

PMID- 11312773
TI  - NMR and MS analysis of decomposition compounds produced from N-acetyl-L-glutamine
      at low pH.
AB  - N-Acetyl-L-glutamine decomposition products glutamine, glutamic acid,
      pyroglutamic acid, N-acetylglutamic acid, and a novel compound, N-(2,6-dioxo-3
      piperidinyl) acetamide, have been identified by NMR and MS techniques. N
      Acetylglutamine, a modified amino acid, offers greater chemical stability than
      glutamine in conditions that are experienced during typical sterilization and
      shelf storage of liquid nutritionals. However, to support safety and stability
      studies, potential decomposition products of N-acetyl-L-glutamine needed to be
      identified. Therefore, atypically harsh conditions were used; an unbuffered (pH
      <3) 1 mg/mL water solution of N-acetyl-L-glutamine was heated to 100 degrees C
      for 3 h. One-dimensional proton and proton-decoupled carbon-13 NMR and
      electrospray LC-MS/MS techniques were employed to identify the molecular
      structures of the generated N-acetyl-L-glutamine decomposition products.
      Additionally, DEPT and two-dimensional NMR techniques TOCSY, GMQCOSY, GHSQC, and
      GHMBC were employed to derive the final structure of the acetamide.

PMID- 11312774
TI  - Neonicotinoid insecticides: molecular features conferring selectivity for insect
      versus mammalian nicotinic receptors.
AB  - The favorable selective toxicity of neonicotinoid insecticides (represented here
      by imidacloprid, thiacloprid, and a nitromethylene analogue) for insects versus
      mammals is not shared by three of their N-unsubstituted imine derivatives or by
      nicotine or epibatidine. The same selectivity pattern is evident at the receptor
      level, i.e., the insect nicotinic acetylcholine receptor (nAChR) versus mammalian
      nAChR subtypes (alpha1, alpha3, alpha4, and alpha7) assayed independently. The
      insect-selective compounds are not protonated with a nitroimine, cyanoimine, or
      nitromethylene group and the mammalian-selective compounds are ionized at
      physiological pH. We propose that the negatively charged tip of the nitro or
      cyano group (not a partial positive charge at imidazolidine N-1 as suggested
      earlier) interacts with a putative cationic subsite of the insect nAChR. This
      contrasts with the mammalian nAChRs where the iminium cation (+C-NH2 <--> C
      =+NH2) of the neonicotinoid imine derivatives or ammonium nitrogen of nicotine or
      epibatidine interacts with the anionic subsite.

PMID- 11312775
TI  - Behavioral responses of the diamondback moth, Plutella xylostella, to green leaf
      volatiles of Brassica oleracea subsp. capitata.
AB  - Green leaf volatiles (GLVs) from Brassica oleracea subsp. capitata L. have been
      identified as 1-hexanol, (Z)-3-hexen-1-ol, 1-hexen-3-ol, hexanal, (E)-2-hexenal,
      hexyl acetate, and (Z)-3-hexenyl acetate, by their mass spectra and retention
      times in comparison with authentic samples. No isothiocyanates were found in the
      extract. The activity of these chemicals has been determined on mated and unmated
      males and females of the diamondback moth (DBM) Plutella xylostella in the
      laboratory (wind tunnel) and in the field. On unmated males, mixtures of (Z)-3
      hexenyl acetate, (E)-2-hexenal, and (Z)-3-hexen-1-ol with the pheromone induced
      attractant/arresting behavior in 80-100% of the males tested, significantly
      higher than the effect induced by the pheromone alone. On mated males and unmated
      females the effect of the GLVs alone or in combination with the pheromone was
      poor, while on mated females these compounds elicited upwind flight and arresting
      behavior in 40-60% of the females assayed. There was no synergism when these
      chemicals were mixed with the pheromone. In the field, (Z)-3-hexenyl acetate, the
      most active GLV in laboratory tests, when mixed with the pheromone in 1:1 ratio,
      enhanced 6-7-fold the number of females and 20-30% the number of males caught by
      traps over those baited with the pheromone alone. Our results indicate that the
      enhancement of the attraction of both males and females of the DBM to traps
      baited with pheromone blended with the relatively inexpensive and environmentally
      safe (Z)-3-hexenyl acetate may be important for future control strategies of the
      pest.

PMID- 11312776
TI  - Stereochemical composition of clenbuterol residues in edible tissues of swine.
AB  - A gas chromatography-mass spectrometry method was developed to measure the
      stereochemical residues of clenbuterol derivatives in edible tissues of swine.
      Clenbuterol present in tissue extracts was derivatized with phosgene to form
      clenbuterol oxazolidin-3-one, which was then separated into component enantiomers
      using a dimethyl beta-cyclodextrin capillary gas chromatographic column. Purified
      clenbuterol stereoisomers, isolated using published liquid chromatographic
      techniques, were used to determine stereoisomer elution order, stereoisomer
      racemization potential, and accuracy of the method. The stereochemical
      composition of clenbuterol could be measured at tissue concentrations of <2 ppb
      using the method. The dextrorotatory stereoisomer was the predominant clenbuterol
      stereoisomer present in edible tissues of hogs slaughtered after withdrawal
      periods of 0, 3, and 7 days, with a (+)/(-) isomer ratio of about 3:1. The
      prevalence of the dextrorotatory stereoisomer in edible tissues of hogs at all
      withdrawal periods suggests that stereoselective processes are occurring during
      the absorption, distribution, metabolism, and (or) excretion of clenbuterol. The
      effect of clenbuterol dose on its stereochemical composition in edible tissues is
      unknown but will be an area of further investigation.

PMID- 11312777
TI  - Constituents and their sweetness of food additive enzymatically modified licorice
      extract.
AB  - Enzymatically modified licorice extract (EMLE) is a natural sweetener, which is
      prepared with cyclodextrin glucanotransferase. It is used because of its unique
      properties such as higher solubility and better taste than those of licorice
      extract. In the present paper, the structures of six major constituents isolated
      from EMLE were determined, and their sweetness was studied. The isolated
      compounds were glycyrrhizin (1), 3-O-[beta-D-glucuronopyranosyl-(1-->2)-beta-D
      glucuronopyranosyl]liquiritic acid (2), and their derivatives glucosylated at the
      C-4 position of the terminal glucuronopyranose with additional one (3 and 4,
      respectively) and two (5 and 6, respectively) glucose moieties. Compounds 1 and 2
      are the major and minor sweet constituents in licorice extract, respectively.
      Compounds 3-6 are new compounds isolated for the first time. Compound 2 was
      sweeter than compound 1. Interestingly, compound 3, which is a monoglucosylated
      derivative of compound 1, was sweeter than compound 4. The sweetness of both
      compounds was lower than that of the parent compounds, while the lingering sweet
      aftertaste was markedly improved. Compounds 5 and 6, which have two additional
      glucose moieties, showed only slight sweetness.

PMID- 11312778
TI  - Studies on the nutritional composition and antinutritional factors of three
      different germplasm seed materials of an under-utilized tropical legume, Mucuna
      pruriens var. utilis.
AB  - Two different germplasms of a white variety and one germplasm of a black variety
      of Mucuna pruriens var. utilis were evaluated for their physicochemical
      properties as well as their nutritional and antinutritional characteristics. All
      germplasms had higher grain weight, density, hydration, and swelling capacity
      than other common legumes. The dehulled samples contained 303.2-335.5 g(-1)
      protein and 46.1-53.5 g x kg(-1) lipid, and these values were higher than the
      respective whole seeds. The levels of macro- and microelements in both whole and
      dehulled seeds were comparable to those in common pulses. All germplasms had a
      high dietary fiber content (18-19.5%), made up of mainly insoluble dietary fiber
      (DF). Seed lipids were high in unsaturated fatty acids (64.7-66.9%), specifically
      linoleic acid (48-49%). Whole and dehulled seeds of the white variety from Salem
      were particularly rich in sulfur-containing amino acids with significantly higher
      levels of in vitro protein digestibility than the other two germplasms. All
      germplasms had high levels of total phenols and phytate, trypsin, and
      chymotrypsin inhibitor activities, but were low in tannins, saponins, and alpha
      amylase inhibitor activity. Only weak hemagglutinating activity against cow
      erythrocytes and no hemagglutinating activity against human erythrocytes (O) was
      observed in all the samples. Dehulled seeds were higher in total starch,
      including resistant starch and oligosaccharides (with verbascose as the major
      fraction) than the respective whole seeds. Both whole and dehulled samples of the
      white variety of Salem germplasm showed significantly lower concentrations of L
      dopa, nonmethylated, and methylated tetrahydroisoquinolines than the respective
      whole and dehulled samples of other germplasms. In general, dehulling didn't
      affect the overall nutritional status in any of the presently investigated
      samples.

PMID- 11312779
TI  - Quantitative HPLC analysis of acids in Brazilian cachacas and various spirits
      using fluorescence detection of their 9-anthrylmethyl esters.
AB  - An analytical procedure for the separation and quantification of 17 short-chain,
      medium-chain, and long-chain acids in cachacas and various spirits has been
      developed involving C18 solid phase extraction, derivatization with 9
      anthryldiazomethane, and reverse phase HPLC using fluorescence detection. The
      limit of detection was between 5 and 15 fmol, whereas the recovery of nonanoic
      acid as internal standard was >95%. Relative standard deviation values for
      reproducibility were between 0.09 and 20.4%, and repeatability was between 0.05
      and 11.3%.

PMID- 11312780
TI  - Nutritionally relevant parameters in low-phytate barley (hordeumvulgare L.) grain
      mutants.
AB  - Nutritionally relevant parameters in barley low-phytate mutant grains were
      analyzed in order to assess the potential value of these lines for future feeding
      trials. Phytate (myo-inositol 1,2,3,4,5,6-hexakisphosphate) levels in grains from
      A- and B-type low-phytate mutants corresponded to 25% and 66% of those of the
      parent line content, respectively. These relative decreases in phytate were
      accompanied by proportional increases of inorganic phosphate amounts. Apart from
      phytate, A-type grains also contained substantial quantities of myo-inositol
      1,3,4,5-tetrakisphosphate. Phytate levels in straw and root material from mutants
      were similar to parent line controls, indicating that low-phytate mutations were
      grain specific. Analysis of K, Mg, Ca, and Zn revealed normal or slightly
      increased mineral cation levels in grains from all low-phytate lines, suggesting
      that mutationally impaired phytate accumulation did not affect mineral storage
      capacity. Other nutritionally important parameters such as starch and protein
      contents were similar to parent line controls. Finally, dynamic changes in the
      phosphorus composition during kernel development suggested that A-type mutations
      directly affected phytate synthesis, whereas B-type mutations seemed to act on
      regulation of synthesis.

PMID- 11312781
TI  - Comparative investigation of concentrations of major and trace elements in
      organic and conventional Danish agricultural crops. 1. Onions (Allium cepa Hysam)
      and peas (Pisum sativum ping pong).
AB  - 210 samples of onions (Allium cepa Hysam) from 11 conventionally and 10
      organically cultivated sites and 190 samples of peas (Pisum sativum Ping Pong)
      from 10 conventionally and 9 organically cultivated sites in Denmark were
      collected and analyzed for 63 and 55 major and trace elements, respectively, by
      high-resolution inductively coupled plasma mass spectrometry. Sampling, sample
      preparation, and analysis of the samples were performed under carefully
      controlled contamination-free conditions. Comparative statistical tests of the
      element concentration mean values for each site show significantly (p < 0.05)
      different levels of Ca, Mg, B, Bi, Dy, Eu, Gd, Lu, Rb, Sb, Se, Sr, Ti, U, and Y
      between the organically and conventionally grown onions and significantly (p <
      0.05) different levels of P, Gd, and Ti between the organically and
      conventionally grown peas. Principal component analysis (PCA) applied to the 63
      elements measured in the individual onion samples from the 21 sites split up the
      sites into two groups according to the cultivation method when the scores of the
      first and third principal components were plotted against each other.
      Correspondingly, for peas, a PCA applied to the 55 elements measured as mean
      values for each site split up the 19 sites into two groups according to the
      cultivation method when the scores of the third and fourth principal component
      were plotted against each other. The methodology may be used as authenticity
      control for organic cultivation after further method development.

PMID- 11312782
TI  - Stilbene content of mature Vitis vinifera berries in response to UV-C
      elicitation.
AB  - A method using HPLC analysis has been used to compare the level of resveratrol
      and its derivatives, piceid, pterostilbene and epsilon-viniferin, in grapevine
      berries of three Vitis vinifera varieties. The concentration of these compounds
      has been evaluated in healthy and Botrytis cinerea infected grape clusters, both
      in natural vineyard conditions and in response to UV elicitation.

PMID- 11312783
TI  - Cross-linking of maize walls by ferulate dimerization and incorporation into
      lignin.
AB  - Cross-linking of xylans and lignin by ferulates was investigated with primary
      maize walls acylated with 2% ferulate and with ferulate ethyl esters. Peroxidase
      mediated coupling of wall ferulate and ethyl ferulate yielded mostly 8-coupled
      products, including three new dehydrodimers. Significant quantities of 5-5
      coupled diferulate formed only within walls, suggesting that matrix effects
      influence dimer formation. Over 60% of wall ferulate dimerized upon H2O2
      addition, suggesting that xylan feruloylation is highly regulated during wall
      biosynthesis to permit extensive dimer formation at the onset of lignification.
      During lignification, ferulate and 5-5-coupled diferulate copolymerized more
      rapidly and formed fewer ether-linked structures with coniferyl alcohol than 8-5
      , 8-O-4-, and 8-8-coupled diferulates. The potential incorporation of most
      ferulates and diferulates into lignin exceeded 90%. As a result, xylans become
      extensively cross-linked by ferulate dimerization and incorporation to lignin,
      but only a small and variable proportion of these cross-links is measurable by
      solvolysis of lignified walls.

PMID- 11312784
TI  - Uptake and phytotransformation of organophosphorus pesticides by axenically
      cultivated aquatic plants.
AB  - The uptake and phytotransformation of organophosphorus (OP) pesticides
      (malathion, demeton-S-methyl, and crufomate) was investigated in vitro using the
      axenically aquatic cultivated plants parrot feather (Myriophyllum aquaticum),
      duckweed (Spirodela oligorrhiza L.), and elodea (Elodea canadensis). The decay
      profile of these OP pesticides from the aqueous medium adhered to first-order
      kinetics. However, extent of decay and rate constants depended on both the
      physicochemical properties of the OP compounds and the nature of the plant
      species. Malathion and demeton-S-methyl exhibited similar transformation patterns
      in all three plants: 29-48 and 83-95% phytotransformation, respectively, when
      calculated by mass recovery balance during an 8-day incubation. No significant
      disappearance and phytotransformation of crufomate occurred in elodea over 14
      days, whereas 17-24% degraded in the other plants over the same incubation
      period. Using enzyme extracts derived from duckweed, 15-25% of the three
      pesticides were transformed within 24 h of incubation, which provided evidence
      for the degradation of the OP compounds by an organophosphorus hydrolase (EC
      3.1.8.1) or multiple enzyme systems. The results of this study showed that
      selected aquatic plants have the potential to accumulate and to metabolize OP
      compounds; it also provided knowledge for potential use in phytoremediation
      processes.

PMID- 11312785
TI  - Uptake and phytotransformation of o,p'-DDT and p,p'-DDT by axenically cultivated
      aquatic plants.
AB  - The uptake and phytotransformation of o,p'-DDT and p,p'-DDT were investigated in
      vitro using three axenically cultivated aquatic plants: parrot feather
      (Myriophyllum aquaticum), duckweed (Spirodela oligorrhiza), and elodea (Elodea
      canadensis). The decay profile of DDT from the aqueous culture medium followed
      first-order kinetics for all three plants. During the 6-day incubation period,
      almost all of the DDT was removed from the medium, and most of it accumulated in
      or was transformed by these plants. Duckweed demonstrated the greatest potential
      to transform both DDT isomers; 50-66% was degraded or bound in a nonextractable
      manner with the plant material after the 6-day incubation. Therefore, duckweed
      also incorporated less extractable DDT (32-49%) after 6 days than did the other
      plants. The capacity for phytotransformation/binding by elodea is between that of
      duckweed and parrot feather; approximately 31-48% of the spiked DDT was degraded
      or bound to the elodea plant material. o,p'-DDD and p,p'-DDD are the major
      metabolites in these plants; small amounts of p,p'-DDE were also found in
      duckweed (7.9%) and elodea (4.6%) after 6 days. Apparently, reduction of the
      aliphatic chlorine atoms of DDT is the major pathway for this transformation.
      This study, which provides new information on plant biochemistry as related to
      pollutant accumulation and phytotransformation, should advance the development of
      phytoremediation processes.

PMID- 11312786
TI  - Fate of quinoxyfen residues in grapes, wine, and their processing products.
AB  - Quinoxyfen is a new fungicide that belongs to the family of the quinolines,
      recently introduced to control powdery mildew (Uncinula necator). In this paper
      the fate of quinoxyfen residues from vine to wine and in their processing
      products was studied. After the last of four applications at the recommended
      rate, 0.38 mg/kg of residue was found on the grapes, which is under the legal
      limit fixed in Italy (0.5 mg/kg). The degradation rate was according to a pseudo
      first-order kinetics (r = 0.964) and the half-life was 7.24 days. Vinification
      was carried out with and without maceration. During the vinifications without
      maceration <50% of the residues passed from the grapes to the musts. Separation
      of the lees (8%) from the must by centrifugation caused no detectable residues in
      centrifuged must. At the end of fermentation with and without maceration no
      quinoxyfen residues were determinable in the wine. No effect on the alcoholic or
      malolactic fermentation was observed even in the presence of higher quinoxyfen
      concentrations than those found in the grapes at harvest time. During
      fermentation, the yeasts partially degraded the pesticides and completly adsorbed
      them. Bacteria, on the other hand, do not have any degradative effect on the
      pesticides. The raisins obtained by sun-drying did not contain any residues,
      whereas those obtained by oven-drying show the same amount of residues as in the
      fresh grapes. During the sun-drying process the fruit weight decreased by a
      factor of 4; the decrease in the oven-drying was equivalent. Samples of dregs and
      liquid lees, fortified with high levels of quinoxyfen. were double-distilled. The
      first dregs distillate, with an alcohol content of 32.1%, did not show any
      residues, whereas the first lees distillate, with an alcohol content of 34.5%,
      showed 7% of the initial residues. After the second lees distillation, the
      obtained product showed an alcoholic content of 81.2% and no residues of
      quinoxyfen (<0.01 mg/kg).

PMID- 11312787
TI  - Biotransformation of vinclozolin by the fungus Cunninghamella elegans.
AB  - This study investigated the biotransformation of the dicarboximide fungicide
      vinclozolin [3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione]
      by the fungus Cunninghamella elegans. Experiments with phenyl-[U-ring
      14C]vinclozolin showed that after 96 h incubation, 93% had been transformed to
      four major metabolites. Metabolites were separated by HPLC and characterized by
      mass and NMR spectroscopy. Biotransformation occurred predominantly on the
      oxazolidine-2,4-dione portion of vinclozolin. The metabolites were identified as
      the 3R- and 3S- isomers of 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutyranilide,
      N-(2-hydroxy-2-methyl-1-oxobuten-3-yl)-3,5-dichlorophenyl-1-carbamic acid, and
      3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide. The enanilide compound has been
      reported previously as a plant and mammalian metabolite and is implicated to
      contain antiandrogenic activity. The 3R- and 3S- isomers of 3',5'-dichloro-2,3,4
      trihydroxy-2-methylbutyranilide are novel metabolites.

PMID- 11312788
TI  - Studies on defatted seed removal efficiency for organochlorine compounds.
AB  - Defatted seeds were evaluated for effective adsorption of organochlorine
      compounds such as chloroform, dichloromethane, and trichloroethylene. The amounts
      of these compounds adsorbed were plotted against the equilibrium concentration of
      substances in solution on a logarithmic scale. A linear relationship was
      obtained, indicating that the adsorption reactions were of the Freundlich type.
      The removal of these organochlorine compounds by defatted seed was attributed to
      the uptake by intracellular particles called spherosomes.

PMID- 11312789
TI  - Nitrification inhibitors from the roots of Leucaena leucocephala.
AB  - The nitrification inhibition (NI) bioassay guided fractionation of the methanol
      extract of lyophilized and milled roots of Leuceana leucocephala resulted in the
      isolation of four compounds, 1-4, as confirmed from their 1H and 13C NMR spectral
      data. Compound 1, gallocatechin, was the most active NI inhibitor at 12
      microg/mL. Epigallocatechin, 2, and epicatechin, 4, isolated as mixtures, were
      not assayed individually for their NI inhibitory activities against the
      nitrification bacterium Nitrosomonas europaea.

PMID- 11312790
TI  - Dynamic deadspace-gas chromatography-olfactometry analysis of different
      anatomical parts of lovage (Levisticum officinale Koch.) at eight growing stages.
AB  - Volatiles of five different parts of lovage (leaves, stems, flowers, seeds, and
      roots) were isolated by dynamic headspace (DHS) method and analyzed by GC-FID and
      GC-olfactometry (GC-O) techniques. In total, 98 compounds were identified in the
      samples, of which 41 are reported as lovage volatiles for the first time.
      Qualitative differences in the composition of DHS constituents of various
      anatomical parts of the plants were not significant, whereas the amounts of a
      number of identified volatile compounds were different in leaves, stems, flowers,
      seeds, and roots. Seasonal variations in the composition of headspace volatiles
      were also determined. Except for roots, beta-phellandrene was found to be the
      most abundant headspace component in all anatomical parts of lovage constituting
      from 36.50% to 79.28% of the total GC peak area. The sniffing panel characterized
      effluents from the GC column, and odor descriptors were attributed to the
      recognized constituents. alpha-Pinene and alpha-phellandrene/myrcene were the
      most frequently recognized constituents among 11 GC effluents constituting 12
      identified compounds and 1 unknown compound, which were detected by the members
      of the sniffing panel. None of the detected constituents was recognized as a
      lovage character impact aroma compound.

PMID- 11312791
TI  - 3-methylthiopropionaldehyde as precursor of dimethyl trisulfide in aged beers.
AB  - Hop S-methylcysteine sulfoxide has previously been postulated as the precursor of
      dimethyl trisulfide (DMTS) in beers. The present data point to 3
      methylthiopropionaldehyde, the Strecker aldehyde issued from methionine, as
      another potential precursor in aged beers. Spiking either fresh beer or wort
      before boiling leads in all cases to higher levels of DMTS after storage.
      Moreover, special malts with a high level of 3-methylthiopropionaldehyde also
      favor polysulfide synthesis. A higher pH should increase this onion-like off
      flavor, whereas a low pH is unfortunately known to enhance the cardboard flavor
      of aged beers. 3-methylthiopropanol, issued from yeast reducing activity, can be
      considered as an additional DMTS source during aging.

PMID- 11312792
TI  - Free and bound volatile composition and characterization of some glucoconjugates
      as aroma precursors in melon de olor fruit pulp (Sicana odorifera).
AB  - Free and glycosidically bound volatiles obtained from the fruit pulp of Sicana
      odorifera by liquid-liquid extraction and by chromatography, followed by
      enzymatic hydrolysis with Rohapect D5L, respectively, were analyzed by capillary
      gas chromatography (HRGC), HRGC-mass spectrometry (HRGC-MS), and HRGC-Olfatometry
      (HRGC-O) analyses. A total of 37 free volatiles was detected, with the major
      components being 3-methyl-2-butanol, 3-hydroxy-2-butanone, ethyl 3
      hydroxybutanoate, and (Z)-3-hexenol. Among the 22 detected glycosidically bound
      compounds, 4-hydroxybenzyl methyl ether, 4-hydroxybenzyl alcohol, and 2
      phenylethanol were found to be the major constituents. Additionally, two
      glucoconjugates were isolated in pure form by multilayer coil countercurrent
      chromatography (MLCCC) of the glycosidic extrac and further purification. Their
      structures were elucidated by MS and NMR analyses to be the novel [4-(beta-D
      glucopyranosyloxy)benzyl] 2,3-dihydroxy-3-methylbutanoate 2, and the known 4
      (beta-D-glucopyranosyloxy)benzyl alcohol 1. Compounds 1 and 2 are precursors of 4
      hydroxybenzyl alcohol, one of the major volatiles generated by enzymatic
      hydrolysis of the glycosidic fraction.

PMID- 11312793
TI  - Production of yarrow (Achillea millefolium L.) in Norway: essential oil content
      and quality.
AB  - In 1996, the production of Achillea millefolium L. at different locations in
      Norway was investigated with regard to the developmental stage. The oil content
      differed greatly between the vegetative stage (0.13%) and the stage of full bloom
      (0.34%). Changes in the composition of yarrow essential oil were found to be
      related to maturation of the plant, with increasing amounts of monoterpenes in
      relation to the sesquiterpene. However, a clear trend could be detected only for
      the monoterpenic compounds with increasing levels of alpha- and beta-pinene and
      alpha-thujone and decreasing levels of sabinene, borneol, and bornyl acetate.
      Previously reported as major compounds, chamazulene and germacrene D could be
      found only in insignificant amounts. A solid-phase microextraction (SPME)
      procedure was applied for screening of the terpenic composition. Sesquiterpenic
      compounds such as beta-bisabolene, alpha-bisabolol, and delta-cadinene were
      detected in substantial amounts by SPME in contrast to the steam-distilled
      samples.

PMID- 11312794
TI  - Free volatile components of passion fruit puree obtained by flash vacuum
      expansion.
AB  - Purple passion fruits were processed by the flash vacuum-expansion process.
      Volatile components were analyzed in purees from steam-heated fruits, steam
      heated then vacuum-expanded fruits and their aromatic liquors, and fruit rind, in
      comparison with a reference single-strength juice. After steam heating, the puree
      was enriched in esters arising from the rind. Steam-heated then vacuum-expanded
      fruits yielded a puree impoverished in volatiles due to evaporation of
      approximately 10% of water. These volatile compounds were mostly recovered in
      aromatic liquors.

PMID- 11312795
TI  - Degradation of oligosaccharides in nonenzymatic browning by formation of alpha
      dicarbonyl compounds via a "peeling off" mechanism.
AB  - The formation of alpha-dicarbonyl-containing substances and Amadori rearrangement
      products was studied in the glycine-catalyzed (Maillard reaction) and uncatalyzed
      thermal degradation of glucose, maltose, and maltotriose using o-phenylenediamine
      as trapping agent. Various degradation products, especially alpha-dicarbonyl
      compounds, are formed from carbohydrates with differing degrees of polymerization
      during nonenzymatic browning. The different Amadori rearrangement products,
      isomerization products, and alpha-dicarbonyls produced by the used carbohydrates
      were quantified throughout the observed reaction time, and the relevance of the
      different degradation pathways is discussed. In the Maillard reaction (MR) the
      amino-catalyzed rearrangement with subsequent elimination of water predominated,
      giving rise to hexosuloses with alpha-dicarbonyl structure, whereas under
      caramelization conditions more sugar fragments with an alpha-dicarbonyl moiety
      were formed. For the MR of oligosaccharides a mechanism is proposed in which 1,4
      dideoxyosone is formed as the predominating alpha-dicarbonyl in the quasi-water
      free thermolysis of di- and trisaccharides in the presence of glycine.

PMID- 11312796
TI  - Reduction of tetrazolium salt XTT by aminoreductone formed during the Maillard
      reaction of lactose.
AB  - Lactose, a reducing disaccharide abundant in milk, reacts extensively with the
      amino groups of protein through the Maillard reaction. The Maillard reaction
      products showed 3'-[1-[(phenylamino)carbonyl]-3,4-tetrazolium]bis(4-methoxy-6
      nitro)benzensulfonic acid hydrate (XTT) reducibility. The objective of this study
      was to clarify the Maillard reaction products responsible for the XTT
      reducibility. When lactose and butylamine were heated at 100 degrees C, the
      characteristic UV maximum at 320 nm was recognized and the relationship between
      the XTT reducibility and the compound with absorption maximum at 320 nm was
      investigated. The time course and the dependence on the heating temperature of
      the formation of the compound with absorption maximum at 320 nm were similar to
      those of the XTT reducibility. Their relationship showed a significant
      correlation (r = 0.967, n = 19). Furthermore, the spectrum change of the heated
      model solution by the addition of XTT suggested that the compound with absorption
      maximum at 320 nm would be involved in the reduction of XTT. Because the compound
      with absorption maximum at 320 nm was identified as an aminoreductone, 1
      (butylamino)-1,2-dehydro-1,4-dideoxy-3-hexulose, by NMR analysis, it can be
      concluded that this was the main XTT-reducing substance.

PMID- 11312797
TI  - Identification of new heterocyclic nitrogen compounds from glucose-lysine and
      xylose-lysine maillard model systems.
AB  - Aqueous sugar (glucose or xylose)-lysine model systems were heated at 80 degrees
      C for 6 h with the pH maintained at a predetermined value (3, 4, or 5). Selected
      compounds were isolated by combinations of solvent extraction and semipreparative
      HPLC, prior to identification by NMR and mass spectrometry. Two compounds were
      identified from the pH 5 glucose system and were identified as epsilon-[2-formyl
      5-(hydroxymethyl)pyrrole-1-yl]-L-norleucine (pyrraline) and the new compound, 1
      (5-carboxy-5-aminopentyl)-2-formyl-3-(1,2,3-trihydroxypropyl)pyrrole. A third
      compound was partially characterized. 2-Acetyl-5-hydroxymethyl-5,6-dihydro-4H
      pyridinone was identified in the pH 3 xylose system, and the new compound, 8
      furan-2-yl-methyl-5-hydroxymethyl-5,6-dihydro-indolizine-1,7-dione, was
      identified in the pH 4 xylose system. 2-Furfurylidene-4-hydroxy-5-methyl-3(2H)
      furanone was identified in both xylose systems. Mechanisms of formation are
      proposed for the novel compounds.

PMID- 11312798
TI  - In vitro biogeneration of pure thiosulfinates and propanethial-S-oxide.
AB  - A model reaction system was developed for generating pure thiosulfinates and
      propanethial-S-oxide (PTSO) using an isolated alliinase (EC 4.4.1.4) and isolated
      or synthetic alk(en)yl-L-cysteine sulfoxides (ACSO). Reaction yields ranged from
      30 to 60% after 3 h at 21-23 degrees C, and organosulfur reaction products were
      extracted into CHCl3 to yield product preparations of controlled composition. A
      pure thiosulfinate or PTSO was derived from a single ACSO, and a preparation
      containing a mixture of four thiosulfinate species was derived from reaction
      mixtures employing binary ACSO substrate systems. Identities of homologous
      thiosulfinates and PTSO were confirmed by 1H NMR. This approach has the potential
      to be used as a preparative tool for yielding pure thiosulfinates and PTSO to
      facilitate the study of chemical and biological properties of this group of
      compounds or as a means to study the dynamics of organosulfur chemistry in
      preparations from Allium spp.

PMID- 11312799
TI  - The hydrophobic character of peanut (Arachis hypogaea) isoagglutinins.
AB  - Peanut seed lectin (PNA) is widely used to identify tumor-specific antigens on
      the eukaryotic cell surface. In this work PNA was purified by affinity
      chromatography, using a column containing glutaraldehyde-treated human
      erythrocytes, whereas PNA isoforms were purified by hydrophobic interaction
      chromatography using Phenyl-Sepharose. The affinity-purified PNA and its isoforms
      consist of four equal subunits of 24.5 kDa each, all of which agglutinated human
      sialidase-treated erythrocytes equally well; however, differences in their
      relative thermostabilities and sugar specificities for lactose were observed.
      Fractions PNA-I and PNA-II possess higher affinity for lactose residues than the
      more hydrophobic isoforms III and IV. These findings suggest that the differences
      observed in PNA isoagglutinins are due to hydrophobic regions of the protein that
      influence the three-dimensional organization of the molecule as well as its
      thermal stability and sugar specificity.

PMID- 11312800
TI  - Wheat gluten phenolic acids: occurrence and fate upon mixing.
AB  - Ferulic acid (FA, 4.9-17.7 microg/100 mg), sinapic acid (SA, 1.4-3.5 microg/100
      mg), and traces of p-coumaric acid and vanillic acid were detected after
      saponification of six wheat glutens from industrial and pilot-scale origins. FA
      and SA occurred mostly as soluble-bound and insoluble-bound forms according to
      their extractability by acetone/methanol/water (7:7:6, v/v/v). The major part of
      FA (50-95%) was found in the unextractable fraction, whereas SA was mostly
      extractable (64-85%). The carbohydrate contents of the glutens were determined
      also after acid hydrolysis. The highest levels of glucose, arabinoxylan, and FA
      were obtained from the unextractable fractions of the pilot-scale extracted
      glutens, probably in relation with a lower efficiency of washing during
      extraction compared to industrial processes. On the other hand, SA compounds were
      in similar concentrations in all samples, suggesting their involvement in
      specific interactions during gluten protein agglomeration. Saponification of the
      soluble-bound phenolic acids released mainly glucose, whereas a beta-glucosidase
      treatment had no effect. FA and SA extractability, especially that of soluble
      bound ones, decreased strongly in overmixed gluten/water doughs. These low
      molecular weight conjugates of phenolic acids could be involved in the dough
      breakdown phenomenon.

PMID- 11312801
TI  - Influence of jam processing on the radical scavenging activity and phenolic
      content in berries.
AB  - Six selected phenolic aglycons (caffeic and ellagic acids, kaempferol, quercetin,
      myricetin, and morin) in nine types of berries, and their changes as influenced
      by jam processing, have been evaluated using optimized HPLC with diode-array
      detection. The berry samples, fresh and after jam processing, were analyzed, and
      the total amounts of selected phenolics as aglycons were identified and
      determined by acid hydrolysis. Their contents in fresh and jam samples did not
      indicate appreciable changes; therefore, the influence of jam processing on these
      selected phenolics in berries was suggested to be small, and was mostly present
      in berries as several conjugated forms that were glycosylated, esterified, etc.,
      in the samples. The total phenolic content of each sample was also determined by
      the Folin-Ciocalteu method. The three samples of each berry, namely fresh, jam,
      and acid hydrolysate of the berry, had similar total phenolic contents. On the
      other hand, the scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical was measured, and acid hydrolysates showed stronger activity than that of
      the fresh and jam-processed samples for all of the berry types.

PMID- 11312802
TI  - Plasticizer effect on oxygen permeability of beta-lactoglobulin films.
AB  - Plasticizer effect on oxygen permeability (OP) of beta-lactoglobulin (beta-Lg)
      films was studied. Propylene glycol (PG), glycerol (Gly), sorbitol (Sor), sucrose
      (Suc), and polyethylene glycol at MW 200 and 400 (PEG 200 and PEG 400,
      respectively) were studied due to their differences in composition, shape, and
      size. Suc-plasticized beta-Lg films gave the best oxygen barrier (OP < 0.05 cm3 x
      microm/m2 x day x kPa). Gly- and PG-plasticized films had similar OP values, and
      both had higher OP than Sor-plasticized films. PEG 200- and PEG 400-plasticized
      films were the poorest oxygen barriers. Empirical equations including plasticizer
      efficiencies for OP were employed to elucidate the relationships between OP of
      plasticized beta-Lg films and plasticizer type and content. Plasticizer
      efficiency ratios between mechanical and OP properties of beta-Lg films show the
      relative efficiency of plasticizers in modifying mechanical and OP properties. A
      large ratio is desirable.

PMID- 11312803
TI  - Investigation on the formation and the determination of gamma-glutamyl-beta
      alanylhistidine and related isopeptide in the macromolecular fraction of beef
      soup stock.
AB  - To confirm the formation of gamma-glutamyl-beta-alanylhistidine and related
      peptide, a model solution (amide-containing amino acids and carnosine) has been
      heated, and the products are investigated. Spectroscopical analysis indicates
      that the major product from asparagine and carnosine is beta-aspartyl-beta
      alanylhistidine, and that from glutamine and carnosine is gamma-glutamyl-beta
      alanylhistidine. Furthermore, to confirm the increase of the above peptides
      during the heating process of food, an HPLC method for the determination of these
      isopeptides in food protein is constructed. The isopeptides are liberated by
      proteolytic digestion and fractionated by solid-phase extraction using Toyopack
      IC-SP cartridges. The fraction containing the isopeptides is derivatized with
      phenylisothiocyanate (PITC) and separated and quantified by HPLC using an
      octadecyl-silica column. As a result of quantification, an increase of the gamma
      glutamyl-beta-alanylhistidine isopeptide in the macromolecular fraction of heated
      beef soup stock solution has been observed. These results suggest that the
      formation of the isopeptide occurs in the heating of various foods containing
      carnosine.

PMID- 11312804
TI  - Determination of phylloquinone and menaquinones in animal products with
      fluorescence detection after postcolumn reduction with metallic zinc.
AB  - A high-performance liquid chromatographic (HPLC) method for the determination of
      phylloquinone and menaquinones in foods of animal origin is described. The K
      vitamers were quantified with a fluorescence detector after postcolumn reduction
      with metallic zinc using K1(25) as an internal standard. Extraction was done
      either with 2-propanol-hexane (meat and fish products) or with acid hydrolysis
      method (dairy products). Prior to quantification, sample extracts were purified
      by semipreparative HPLC; in addition, the fats of cheese and rainbow trout
      samples were removed with lipase hydrolysis. By this method the phylloquinone and
      menaquinones (MK-4 to MK-10) present in a few representative samples of different
      animal food groups were determined. HPLC-MS was used to confirm the
      identification of K vitamers. Long-chain menaquinones were found from bovine and
      pig livers as well as from various cheeses. The total vitamin K contents
      calculated as the sum of quantified K vitamers were in general low (mean content
      10-100 ng/g); the highest amount was analyzed in chicken meat (600 ng/g).

PMID- 11312805
TI  - Induction of apoptosis by the oolong tea polyphenol theasinensin A through
      cytochrome c release and activation of caspase-9 and caspase-3 in human U937
      cells.
AB  - This study examined the growth inhibitory effects of theasinensin A (from oolong
      tea) and black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of
      theaflavin-3-gallate (TF-2a) and theaflavin-3'-gallate (TF-2b), and theaflavin
      3,3'-digallate (TF-3) in human cancer cells. Theasinensin A, TF-1, and TF-2
      displayed strong growth inhibitory effects against human histolytic lymphoma
      U937, with estimated IC50 values of 12 microM, but were less effective against
      human acute T cell leukemia Jurkat, whereas TF-3 and (-)-epigallocatechin-3
      gallate (EGCG) had lower activities. The molecular mechanisms of tea polyphenol
      induced apoptosis as determined by annexin V apoptosis assay, DNA fragmentation,
      and caspase activation were further investigated. Loss of membrane potential and
      reactive oxygen species (ROS) generation were also detected by flow cytometry.
      Treatment with tea polyphenols caused rapid induction of caspase-3, but not
      caspase-1, activity and stimulated proteolytic cleavage of poly(ADP-ribose)
      polymerase (PARP). Pretreatment with a potent caspase-3 inhibitor, Z-Asp-Glu-Val
      Asp-fluoromethyl ketone, inhibited theasinensin A induced DNA fragmentation.
      Furthermore, it was found that theasinensin A induced loss of mitochondrial
      transmembrane potential, elevation of ROS production, release of mitochondrial
      cytochrome c into the cytosol, and subsequent induction of caspase-9 activity.
      These results indicate that theasinensin A allows caspase-activated
      deoxyribonuclease to enter the nucleus and degrade chromosomal DNA and induces
      DFF-45 (DNA fragmentation factor) degradation. The results suggest that induction
      of apoptosis by theasinensin A may provide a pivotal mechanism for their cancer
      chemopreventive function.

PMID- 11312806
TI  - Comparative evaluation of antioxidant potential of alaternin (2-hydroxyemodin)
      and emodin.
AB  - The antioxidant activities of alaternin (2-hydroxyemodin) and emodin were
      compared for their respective potentials to inhibit lipid peroxidation in the
      linoleic acid system by the thiocyanate method, to inhibit total reactive oxygen
      species generation in kidney homogenates using 2',7'-dichlorodihydrofluorescein
      diacetate, to inhibit peroxynitrite formation by the 3-morpholinosydnonimine
      system, which generates superoxide radical and nitrogen monooxide, and to
      scavenge authentic peroxynitrites. Both alaternin and emodin were found to
      inhibit the peroxidation of linoleic acid by the thiocyanate method in a dose
      dependent manner. Whereas the former shows inhibitory activities in reactive
      oxygen- and nitogen-mediated reactions, the latter does not. These results
      indicate that alaternin is a potentially effective and versatile antioxidant and
      can be used to protect biological systems and functions against various oxidative
      stresses.

PMID- 11312807
TI  - Resveratrol and piceid levels in natural and blended peanut butters.
AB  - Peanut and its derivatives, especially peanut butter, are extensively consumed in
      many countries, mainly in the United States, which is also the major exporter of
      these products. trans-Resveratrol is present in peanuts, and recently this
      compound has been quantified in peanut butter. It is well-known that there are
      beneficial effects of trans-resveratrol and its glucoside, the piceid, in health.
      The absorption of trans-resveratrol has been proven in animals, and certain
      studies show that the absorption of some phenols is enhanced by conjugation with
      glucose, so that it could be possible that trans-piceid would be more absorbed
      than its aglycon (trans-resveratrol). In our work, we have identified the
      presence of trans-piceid in peanut butter with a new method to quantify trans
      resveratrol and trans-piceid (3-beta-glucose of trans-resveratrol). This fact is
      very interesting because the glucosilated form could be more easily absorbed by
      the intestinal gut; in this way trans-piceid would exercise its beneficial
      function more efficiently than trans-resveratrol. To our knowledge, this is the
      first time that trans-piceid has been quantified in peanut butter. Resveratrol
      and piceid contents in natural peanut butters were found to be significantly
      higher than those in blended peanut butters.

PMID- 11312808
TI  - Effects of tea catechins on the ERE-regulated estrogenic activity.
AB  - Tea catechins exert many biological effects, including anticancer and
      antibacterial activities. Also, it is reported that some plant flavonoids exhibit
      estrogenic activity. In this study, we investigated estrogenic or antiestrogenic
      activities of catechins in HeLa cells transiently transfected with an estrogen
      response element (ERE)-regulated luciferase reporter and an estrogen receptor
      (ER) alpha or ERbeta expression vector. Catechins alone did not induce luciferase
      (luc) activity in either of the ERs. Addition of 17beta-estradiol (E2) plus
      epicatechin gallate (ECG) or epigallocatechin gallate (EGCG) at 5 x 10(-6) M
      resulted in significant decreases in the ERalpha-mediated luc activity compared
      with that of E2 alone. On the contrary, lower concentrations significantly
      increased the E2-induced luc activity. Similar effects were observed with
      tamoxifen. The ERbeta-mediated estrogenic activities were stimulated by
      catechins. In conclusion, some catechins, particularly EGCG, were antiestrogenic
      for ERalpha at higher doses, and co-estrogenic for ERalpha at lower doses and for
      ERbeta. The lower doses were found in human plasma after tea-drinking. In
      addition, some catechins may be antiendocrine disruptors because they suppressed
      bisphenol A-induced luc activities.

PMID- 11312809
TI  - Effect of dietary conjugated linoleic acid on lipid peroxidation and histological
      change in rat liver tissues.
AB  - The effect of dietary conjugated linoleic acid (CLA) on hepatic lipid parameters
      in Sprague-Dawley rats was examined. When rats were fed a diet containing CLA at
      0 (control), 1, or 2% of the weight of the amount of food given for 3 weeks, the
      liver weight exhibited a slight increase in the CLA-fed groups, although the
      difference was not significant. Lipid accumulation in the hepatocytes of CLA-fed
      rats was also demonstrated by electron microscopic observation. In addition, the
      liver thiobarbituric acid reactive substances levels were significantly higher in
      the 2 wt % CLA group than in the other two dietary groups, and the levels of
      phosphatidylcholine hydroperoxide were higher in CLA-fed groups when compared to
      that of the control group. On the other hand, the serum lipid peroxide levels
      were comparable among all three dietary groups. Levels of triglycerides in the
      white adipose tissue (WAT) and serum nonesterified fatty acid (NEFA) were reduced
      in a CLA-dose-dependent manner. CLA was shown to accumulate in the WAT much more
      than in the serum or liver. These results suggest that CLA accelerates the
      decomposition of storage lipids in WAT and the clearance of serum NEFA levels,
      resulting in lipid peroxidation and a morphological change in the liver.

PMID- 11312810
TI  - Lipid fractions with aggregatory and antiaggregatory activity toward platelets in
      fresh and fried cod (Gadus morhua): correlation with platelet-activating factor
      and atherogenesis.
AB  - Cod (Gadus morhua) is a popular part of the diet in many countries on both sides
      of the North Atlantic; in most cases it is consumed fried. In this study, total
      lipids of cod muscle were separated into neutral and polar lipids, which were
      further fractionated by HPLC. The lipid fractions were tested in vitro, against
      washed rabbit platelets, for the probable existence of lipid compounds that
      either exhibit an action similar to that of platelet-activating factor (PAF) or
      inhibit the action of PAF. The platelet bioassay was used to evaluate total
      lipids, total polar lipids, and total neutral lipids, before any further
      separation. Detection of these compounds in fresh and fried cod could be used to
      evaluate the nutritional value of this important fish. The in vitro biological
      study of lipids showed that in fresh cod lipid fractions, ranges of PAF-like and
      anti-PAF-like activities were present, whereas in fried cod lipid fractions, both
      neutral and polar, anti-PAF activities were mainly observed. Because it has
      already been reported that PAF is involved in atheromatosis generation, the
      existence of PAF inhibitors in cod may contribute to the possible protective role
      of fish, in this case cod, against atherosclerosis.

PMID- 11312811
TI  - Inhibition of radical reaction of apolipoprotein B-100 and alpha-tocopherol in
      human plasma by green tea catechins.
AB  - (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg),
      (-)-epigallocatechin gallate (EGCg), and Trolox inhibited the decreases of
      apolipoprotein B-100 (apoB) and alpha-tocopherol in a radical reaction of human
      plasma initiated by Cu(2+). The concentrations of EC, EGC, ECg, EGCg, and Trolox
      for 50% inhibition (IC50) of apoB fragmentation were 39.1, 42.2, 14.6, 21.3, and
      36.2 microM, respectively. Similar IC50 values were observed for alpha-tocopherol
      consumption, indicating the close relationship between apoB fragmentation and
      alpha-tocopherol consumption. These results demonstrate that tea catechins serve
      as an effective antioxidant in plasma and that the gallate group has a strong
      antioxidative activity.

PMID- 11312812
TI  - Isolation and characterization of endothelium-dependent vasorelaxing compounds
      from grape seeds.
AB  - Previous work has shown that red wines, grape juices, and other grape products
      cause endothelium-dependent relaxation (EDR) of blood vessels in vitro by
      increasing nitric oxide production. In this paper we describe the isolation and
      characterization of some of the compounds responsible for EDR activity. Concord
      grape seeds were extracted with methanol and the compounds were separated by
      Toyopearl TSK HW-40S chromatography. Resulting fractions (primarily phenolic
      acids, catechins, and proanthocyanidins) were further separated semipreparatively
      by reversed-phase HPLC, and peaks were collected and bioassayed for EDR activity
      using the rat aorta preparation. EDR-active compounds were subsequently
      characterized by HPLC retention times and electrospray-ion-trap mass
      spectrometry. The compounds exhibiting the most EDR activity were
      proanthocyanidin trimers, tetramers, pentamers, and polymers and their gallates,
      as well as a dimer gallate (EC50 values in the range of 0.6-2.5 microg catechin
      equivalents/mL). These compounds should be useful for in vitro and in vivo
      studies, particularly as they relate to improvement of cardiovascular function.

PMID- 11312814
TI  - Status and Prospects-2001.

PMID- 11312815
TI  - Nutritional and health benefits of soy proteins.
AB  - Soy protein is a major component of the diet of food-producing animals and is
      increasingly important in the human diet. However, soy protein is not an ideal
      protein because it is deficient in the essential amino acid methionine.
      Methionine supplementation benefits soy infant formulas, but apparently not food
      intended for adults with an adequate nitrogen intake. Soy protein content of
      another essential amino acid, lysine, although higher than that of wheat
      proteins, is still lower than that of the milk protein casein. Adverse
      nutritional and other effects following consumption of raw soybean meal have been
      attributed to the presence of endogenous inhibitors of digestive enzymes and
      lectins and to poor digestibility. To improve the nutritional quality of soy
      foods, inhibitors and lectins are generally inactivated by heat treatment or
      eliminated by fractionation during food processing. Although lectins are heat
      labile, the inhibitors are more heat-stable than the lectins. Most commercially
      heated meals retain up to 20% of the Bowman-Birk (BBI) inhibitor of chymotrypsin
      and trypsin and the Kunitz inhibitor of trypsin (KTI). To enhance the value of
      soybeans in human nutrition and health, a better understanding is needed of the
      factors that impact the nutrition and health-promoting aspects of soy proteins.
      This paper discusses the composition in relation to properties of soy proteins.
      Also described are possible beneficial and adverse effects of soy-containing
      diets. The former include soy-induced lowering of cholesterol, anticarcinogenic
      effects of BBI, and protective effects against obesity, diabetes, irritants of
      the digestive tract, bone, and kidney diseases, whereas the latter include poor
      digestibility and allergy to soy proteins. Approaches to reduce the concentration
      of soybean inhibitors by rearrangement of protein disulfide bonds, immunoassays
      of inhibitors in processed soy foods and soybean germplasm, the roles of
      phytoestrogenic isoflavones and lectins, and research needs in all of these areas
      are also discussed. This integrated overview of the widely scattered literature
      emphasizes general concepts based on our own studies as well as recent studies by
      others. It is intended to stimulate interest in further research to optimize
      beneficial effects of soy proteins. The payoff will be healthier humans and
      improved animal feeds.

PMID- 11312816
TI  - Development of an indirect competitive ELISA for ciprofloxacin residues in food
      animal edible tissues.
AB  - An indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed
      to detect ciprofloxacin (CPFX) in food animal edible tissues. CPFX was converted
      by an active ester method into conjugates CPFX-bovine serum albumin (CPFX-BSA)
      and CPFX-human serum albumin (CPFX-HSA), which both allowed production of CPFX
      specific rabbit antisera. In the ELISA, CPFX-HSA was coated onto the microtiter
      plate, followed by incubation with standard CPFX and anti-CPFX antibody. The
      indirect competitive ELISA revealed that the antisera have no cross-reactivity
      with penicillin, gentamicin, neomycin, sulfadiazine, and chlortetracycline. The
      antisera cross-reacted with enrofloxacin and norfloxacin about 69.8 and 44.6% as
      much as they did with CPFX. This ELISA was highly sensitive (0.32 ng/mL) to CPFX
      determination. Recovery of CPFX at 40 microg/kg was 75.58% in pork, 81.29% in
      chicken, and 84.30% in milk. The coefficients of variation varied from 3.7 to
      9.2% over the range of CPFX concentrations studied. The linear detection range
      was between 1.6 and 1000 ng/mL. The results suggest that this ELISA is a
      specific, accurate, and convenient method for the detection of CPFX residues in
      food animal edible tissues.

PMID- 11312817
TI  - Determination of ETU in tomatoes and tomato products by HPLC-PDA: evaluation of
      cleanup procedures.
AB  - An HPLC-PDA method for the determination of ethylenethiourea (ETU), the main
      degradation product of the organic fungicides ethylene bis(dithiocarbamate)s
      (EBDCs), in tomatoes and tomato products is reported. Solid-matrix liquid-liquid
      (l-l) partitioning and separatory funnel l-l partitioning for the cleanup were
      examined. The effect of salt addition, pH, and phase ratio on analyte recovery at
      the cleanup step was studied. It was found that solid-matrix l-l partitioning
      afforded higher precision and more selective separation of the analyte. According
      to the method proposed, the samples were extracted with methanol/water (3:1, v/v)
      and cleaned up on an Extrelut 20 column. ETU was eluted with dichloromethane and
      separated on a reversed phase HPLC column. For tomato products with degrees Brix
      > 20 further purification through silica cartridge was adopted. The method was
      validated over the following ranges of concentrations: 0.01-0.5 mg/kg for
      tomatoes, 0.01-0.1 mg/kg for tomato juice, and 0.05-0.25 mg/kg for tomato paste.
      The accuracy (recoveries > 70%) and the precision obtained (%RSD < 10%) were
      satisfactory.

PMID- 11312818
TI  - Determination of bisphenol A in food-simulating liquids using LCED with a
      chemically modified electrode.
AB  - Liquid chromatography with electrochemical detector (LC-ED), using a chemically
      modified electrode coated with a metalloporphyrin film, is reported for
      determination of bisphenol A (BPA) migration from polycarbonate baby bottles. The
      extraction process of the samples was performed according to regulations of the
      Southern Common Market (MERCOSUR), where certain food-simulating liquids [(A)
      distilled water, (B) acetic acid 3% V/V in distilled water, and (C) ethanol 15%
      V/V in distilled water] are defined along with controlled time and temperature
      conditions. The baseline obtained using the naked electrode showed a considerable
      drift which increased the detection limit. This effect was suppressed with the
      chemically modified electrode. A linear range up to 450 ppb along with a
      detection limit of 20 ppb for the amperometric detection technique was observed.
      The procedure described herein allowed lowering the detection limit of the method
      to 0.2 ppb. The value found for BPA in the food-simulating liquid is 1.2 ppb,
      which is below the tolerance limit for specific migration (4.8 ppm).

PMID- 11312819
TI  - Analysis of limonoid glucosides from citrus by electrospray ionization liquid
      chromatography-mass spectrometry.
AB  - An electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS)
      method for the detection and quantitation of limonoid glucosides has been
      developed. Negative ions [M - H(+)](-) characteristic of six limonoid glucosides
      can be detected and quantified from selected ion monitoring chromatograms using
      carminic acid as an internal standard. The described method has been applied to
      the analysis of limonoid glucoside content in various liquid and solid Citrus
      spp. samples as well as complex mixtures of partially purified limonoid
      glucosides. Rapid and sensitive qualitative screening of samples for limonoid
      glucosides can also be accomplished with slight modifications of the method.

PMID- 11312820
TI  - Multiresidue screening of pesticides in fruits using an automatic solid-phase
      extraction system.
AB  - About 20 pesticides were determined in lyophilized fruits using a semiautomatic
      multiresidue method, based on solid-phase extraction (SPE) with a silica column.
      The lyophilization of the sample, besides the SPE procedure selected, provided
      clean extracts despite the complexity of the matrixes studied. In addition, the
      lyophilization process allows sample preservation for at least three months
      without changes in the concentrations of the pesticides. Determination and
      quantitation of organochlorine and pyrethroid residues was carried out using a
      gas chromatograph equipped with an electron capture detector (GC-ECD), and a mass
      spectrometric detector (GC-MS) was used for confirmation purposes. Organochlorine
      pesticides provided average recoveries (spiked at three concentration levels in
      eight different fruits) near 93 +/- 4%, being lower (89 +/- 8%) for pyrethroids
      as a consequence of their higher degradation and interaction with the sample
      matrix. On the other hand, the detection limits achieved for all pesticides (0.5
      8 ng per g of lyophilized fruit) allow their determination at the MRLs
      established by the European Union, with good precision ( approximately 5%).
      Finally, from the 100 different fruits screened, only 10 positive responses were
      obtained, which were further confirmed by GC-MS.

PMID- 11312821
TI  - Improved method to track chlorophyll degradation.
AB  - An analytical method capable of identifying >30 chlorophyll-related compounds in
      plant extracts has been developed. The method employs liquid chromatography
      coupled to UV-vis, MS, and MS/MS detection. It can be applied without
      modification to analyze natural chlorophyll degradation products and other
      metalloporphyrines. It was successfully applied to identify chlorophyll
      derivatives found in rehydrated spinach powder and conventionally canned and Veri
      Green-processed beans. In the Veri-Green-processed beans several degradation
      products were identified that are zinc-containing analogues to the chlorophyll
      derivatives found in vegetables after conventional canning. They have been
      characterized by liquid chromatography and mass spectrometry.

PMID- 11312822
TI  - Steady-state and time-resolved spectroscopy of F420 extracted from methanogen
      cells and its utility as a marker for fecal contamination.
AB  - Methanogenic bacteria, which are common inhabitants of the animal digestive
      tract, contain the fluorescent compound F420 (coenzyme 420), a 7,8-didemethyl-8
      hydroxy-5-deazariboflavin chromophore. F420 was characterized as an initial step
      in determining if this compound would be useful as a fluorescent marker for the
      detection of fecal and ingesta contamination. Using a single anion exchange
      chromatographic process, F420 was separated from other cell components of a
      Methanobrevibacter sp. cell culture. The extent of separation was determined
      spectroscopically. To aid in the development of possible techniques for the
      detection of fecal contamination using F420 as a marker, further spectroscopic
      investigation of F420 was conducted using steady-state and time-resolved
      fluorescence methods. The fluorescence lifetime of F420 in an elution buffer of
      pH 7.5 was found to be 4.2 ns. At higher pH values, the fluorescence decay, F(t),
      was best described by a sum of two exponentials: at pH 13, F(t) = 0.31 exp(
      t/4.20 ns) + 0.69 exp(-t/1.79 ns). Further investigation using front-faced
      fluorescence techniques has shown that emission from F420 can be collected
      efficiently from samples of methanogen cell cultures as well as from fecal
      material.

PMID- 11312823
TI  - Pyrolysis-GC-MS analysis of the formation and degradation stages of charred
      residues from lignocellulosic biomass.
AB  - The structural transformations undergone by lignocellulosic biomass (freeze-dried
      rye grass, Lolium rigidum) subjected to progressive isothermal heating (burning
      at 350 degrees C under oxidizing conditions for 30, 45, 60, 75, and 90 s) have
      been monitored by Curie-point pyrolysis-gas chromatography-mass spectrometry (Py
      GC-MS). The pyrograms suggest that even charred residues after severe heating
      (carbon loss ca. 50%) still contain substantial concentrations of some resistant
      plant structural components. Several trends were observed when monitoring the
      relative concentrations of the different groups of pyrolysis compounds released
      during successive charring stages: (i) the tetrapyrrole moiety of chlorophylls is
      rapidly destroyed as indicated by the decreasing yields of pyrroles and
      pyrrolines, whereas the phytol backbone is comparatively more resistant, leading
      to phytadienes after dehydration and reduction; (ii) the increasing yields of
      imidazoles from progressively heated samples (maximum at 45 s stage) suggest
      accumulation of newly formed nitrogen-containing compounds that may survive
      natural fires; (iii) the lignin backbone shows a relative resistance, the yields
      of aromatic products pointing to progressive demethoxylation; and, (iv) a
      selective accumulation of recalcitrant alkyl material occurred, which is
      interpreted as the result of thermal condensation of hydrocarbons and fatty acids
      into macromolecular materials in the charred residue. In terms of the intensity
      of the isothermal heating, the yields of the different classes of alkyl compounds
      follow the order phytadienes < fatty acids < alkanes < wax esters < sterols.

PMID- 11312824
TI  - Characterization of cigar tobaccos by gas chromatographic/mass spectrometric
      analysis of nonvolatile organic acids: application to the authentication of Cuban
      cigars.
AB  - A reliable method based on gas chromatographic/mass spectrometric (GC/MS)
      profiling of nonvolatile organic acids is described for the characterization of
      cigars. The method involves an aqueous extraction of ground tobacco and selective
      isolation of the acids by simply stirring strong anion exchange (SAX) disks in
      the aqueous tobacco extract. The acids are then directly silylated on the disk
      with N-methyl-N-trimethylsilyl-trifluroacetamide (MSTFA) in acetonitrile in an
      autosampler vial. Elution of the derivatized acids in situ allows the sample to
      be directly analyzed by GC/MS without further sample handling. Compared to the
      conventional disk-extraction technique using a vacuum manifold, this method is
      much less labor intensive, and is desirable for multiple sample analysis.
      Nicotinic acid, succinic acid, glyceric acid, malic acid, pyroglutamic acid,
      threonic acid, citric acid, uracil, and an unidentified acid were reproducibly
      quantified in tobacco samples. Principal component analysis (PCA) of the acid
      profiles of the filler tobaccos of 18 Cuban cigars and 31 non-Cuban cigars shows
      separation of the two groups, indicating that the acid profiles are potentially
      useful in the authentication of Cuban cigars.

PMID- 11312825
TI  - Rapid method for the discrimination of red wine cultivars based on mid-infrared
      spectroscopy of phenolic wine extracts.
AB  - Mid-infrared spectroscopy and UV-vis spectroscopy combined with multivariate data
      analysis have been applied for the discrimination of Austrian red wines,
      including the cultivars Cabernet Sauvignon, Merlot, Pinot Noir, Blaufrankisch
      (Lemberger), St. Laurent, and Zweigelt. Both authentic wines and their phenolic
      extracts were investigated by attenuated total reflectance (ATR)-mid-infrared
      spectroscopy. Phenolic extracts were also investigated by UV-vis spectroscopy.
      The wine extracts were obtained by solid-phase extraction with C-18 columns and
      elution by methanol containing 0.01% hydrochloric acid. Hierarchical cluster
      analysis was performed with mid-infrared spectra of both wines and extracts, as
      well as with UV-vis spectra of the phenolic extracts. Data processing involved
      vector normalization and derivation of the spectra. Due to varying concentrations
      of main components including sugar and organic acids, satisfactory classification
      of untreated wines was not achieved. However, when using mid-infrared spectra of
      the phenolic extracts, almost complete discrimination of all cultivars
      investigated was achieved. The use of UV-vis spectroscopy for cultivar
      discrimination was found to be limited to the authentication of the Burgundy
      species Pinot Noir. In addition, soft independent modeling of class analogy was
      applied to the mid-infrared spectra of the extracts. It was possible to establish
      class models for five different wine cultivars and to classify test samples
      correctly.

PMID- 11312826
TI  - Orange, mandarin, and hybrid classification using multivariate statistics based
      on carotenoid profiles.
AB  - A study was undertaken to differentiate citrus on the basis of a carotenoid
      profile obtained from the HPLC determination of 12 carotenoids found in
      saponified fresh juice. Mandarin, orange, and various hybrid varieties were
      analyzed to determine their carotenoid profiles. The resulting peak areas were
      analyzed using principal component analysis (PCA), canonical discriminate
      analysis (CDA), and Mahalanobis distances. These were used to develop models for
      classifying the juices into appropriate groups. Thirty-two samples were analyzed
      to determine classification techniques. Mandarin and orange juices were quite
      distinct, with the hybrids scattered throughout the mandarin and orange clusters
      using PCA. CDA resulted in three distinct groups with only a few of the hybrids
      in the orange grouping.

PMID- 11312827
TI  - Immunoaffinity purification of chlorimuron-ethyl from soil extracts prior to
      quantitation by enzyme-linked immunosorbent assay.
AB  - A competitive-indirect enzyme-linked immunosorbent assay (CI-ELISA) was developed
      to quantify chlorimuron-ethyl in soil. The linear working range of the assay was
      from 1 to 1000 ng mL(-)(1). The assay had an I(50) value of 54 ng mL(-)(1), with
      a limit of detection of 2 ng mL(-)(1) and a limit of quantification of 27 ng mL(
      )(1). Three soils were extracted using a carbonate buffer (pH 9.0) and the
      extracts spiked with chlorimuron-ethyl. Because of the effects of coextractants
      (matrix effects) from soil on the accuracy and precision of the ELISA,
      immunoaffinity chromatography (IAC) was used to purify chlorimuron-ethyl from
      soil extracts prior to analysis. The immunoaffinity columns, which had a total
      binding capacity of 1350 ng of chlorimuron-ethyl mL(-)(1) of immunosorbent, were
      prepared by binding anti-chlorimuron-ethyl antibodies to protein G Sepharose 4B.
      Although the matrix effects were largely removed using the affinity column, they
      could be completely removed by first passing the extract through a column
      containing epoxy-coupled 1,6-diaminohexane (EAH) Sepharose 4B to remove organic
      acids prior to IAC. Assay sensitivity was increased 100-fold using IAC to purify
      and simultaneously concentrate chlorimuron-ethyl from soil extracts. The
      purification strategy (EAH followed by IAC chromatography) removed matrix effects
      from all three soils and allowed for the accurate quantitation of chlorimuron
      ethyl in soil extracts.

PMID- 11312828
TI  - Comparison of methylation procedures for conjugated linoleic acid and artifact
      formation by commercial (trimethylsilyl) diazomethane.
AB  - Four different methods for methylating conjugated linoleic acid (CLA) were
      compared. The HCl/MeOH and BF(3)/MeOH methods were tested under different time
      and temperature combinations. Increasing temperature and/or incubation time for
      either method decreased the cis-9,trans-11 and trans-10,cis-12 isomers, but trans
      9,trans-11/trans-10,trans-12 isomers and artifacts (allylic methoxide) were
      increased. In addition, the triacylglyceride form of CLA was tested using the
      above methods and NaOMe at various temperatures for 20 min. The NaOMe did not
      generate methoxy artifacts. However, there were impurities in GC after
      methylation with NaOMe as well as with BF(3)/MeOH. The
      (trimethylsilyl)diazomethane method, which is a mild and easy alternative, was
      tested. Free forms of fatty acids were easily, but not completely, methylated by
      this method. Also, the method generated artifacts (trimethylsilyl CLA esters) and
      impurities (trimethylsilyl) that would interfere with short-chain fatty-acid
      analysis by GC.

PMID- 11312829
TI  - Use of methanolysis for the determination of total ellagic and gallic acid
      contents of wood and food products.
AB  - Anhydrous methanolic HCl has been found to be an excellent reagent for releasing
      ellagic acid and gallic acid (as methyl gallate) from biomass substrates.
      Optimization of both the reaction conditions and the gradient HPLC analysis has
      led to the development of a new protocol. The method provides ellagic acid yields
      significantly higher than those obtained previously, indicating total ellagic
      acid contents of several substrates have previously been underestimated.

PMID- 11312830
TI  - Multivariate calibration for the determination of total azadirachtin-related
      limonoids and simple terpenoids in neem extracts using vanillin assay.
AB  - Two-component and multivariate calibration techniques were developed for the
      simultaneous quantification of total azadirachtin-related limonoids (AZRL) and
      simple terpenoids (ST) in neem extracts using vanillin assay. A mathematical
      modeling method was also developed to aid in the analysis of the spectra and to
      simplify the calculations. The mathematical models were used in a two-component
      calibration (using azadirachtin and limonene as standards) for samples containing
      mainly limonoids and terpenoids (such as neem seed kernel extracts). However, for
      the extracts from other parts of neem, such as neem leaf, a multivariate
      calibration was necessary to eliminate the possible interference from phenolics
      and other components in order to obtain the accurate content of AZRL and ST. It
      was demonstrated that the accuracy of the vanillin assay in predicting the
      content of azadirachtin in a model mixture containing limonene (25% w/w) can be
      improved from 50% overestimation to 95% accuracy using the two-component
      calibration, while predicting the content of limonene with 98% accuracy. Both
      calibration techniques were applied to estimate the content of AZRL and ST in
      different parts of the neem plant. The results of this study indicated that the
      relative content of limonoids was much higher than that of the terpenoids in all
      parts of the neem plant studied.

PMID- 11312831
TI  - Development of a DNA-based method aimed at identifying the fish species present
      in food products.
AB  - Analysis of restriction fragment length polymorphism (RFLP) profiles of a 464 bp
      amplicon obtained from the mitochondrial cytochrome b gene was used to
      differentiate between several different fish species. The method was tested by a
      collaborative study in which 12 European laboratories participated to ascertain
      whether the method was reproducible. Each laboratory was required to identify 10
      unknown samples by comparison with RFLP profiles from authentic species. From a
      total of 120 tests performed, unknown samples were correctly identified in 96% of
      cases. Further work attempting to use the method to analyze mixed and processed
      fish samples was also performed. In all cases the species contained within mixed
      samples were correctly identified, indicating the efficacy of the method for
      detecting fraudulent substitution of fish species in food products.

PMID- 11312832
TI  - Biomechanical and biochemical pulping of sugarcane bagasse with Ceriporiopsis
      subvermispora fungal and xylanase pretreatments.
AB  - Sugarcane bagasse was pretreated with both the white-rot fungus, Ceriporiopsis
      subvermispora, and xylanase enzyme for 2 weeks before soda chemithermomechanical
      (CTMP) and soda chemical (CP) cooking. For fungi-CTMP (BCTMP) and enzyme-fungi
      CTMP (EBCTMP), the bagasse, after bio-pretreatment, was cooked with 5% sodium
      hydroxide, at 130 degrees C for 20 min. For the chemical pulping (CP), after
      fungi pretreatment (BCP) or after xylanase and fungal pretreatment (EBCP), the
      bagasse was cooked with 14.5% sodium hydroxide. With the BCTMP, the Klason lignin
      was reduced, all of the pulp strength properties were increased, and a 28%
      savings in refining energy consumption was obtained, but the brightness was
      reduced 5 points compared to the control. With the EBCTMP, the brightness losses
      were overcome but with a mild reduction in the pulp strength properties compared
      to the BCTMP. The energy savings were 5% greater than from BCTMP and 33% over the
      control. The BCP treatment increases somewhat the pulp strength properties,
      reduces the energy consumption 23%, and reduces the brightness by 9 points
      compared to the control; however, the kappa no. was 5.5 points higher than the
      control. EBCP treatment reduces brightness losses and increases the pulp yield 2%
      compared to the control, but with some reduction in the strength properties
      compared to BCP.

PMID- 11312833
TI  - Synthesis of the antioxidant hydroxytyrosol using tyrosinase as biocatalyst.
AB  - Hydroxytyrosol (HTyr), a natural ortho-diphenolic antioxidant with health
      beneficial properties that mainly occurs in virgin olive oil and olive oil mill
      waste waters (also known as vegetative waters), has been enzymatically
      synthesized using mushroom tyrosinase. This o-diphenol (not commercially
      available) was obtained from its monophenolic precursor tyrosol (commercially
      available) in the presence of both tyrosinase and ascorbic acid. The reaction
      synthesis is continuous, easy to perform, and adaptable to a bioreactor for
      industrial purposes. The HTyr concentration is time-predicted, and the yield of
      reaction can be 100%. The synthesis method reported here is an alternative
      approach to obtain this compound in an environmentally friendly way.

PMID- 11312834
TI  - Identification of anchovy (Engraulis encrasicholus L.) and gilt sardine
      (Sardinella aurita) by polymerase chain reaction, sequence of their mitochondrial
      cytochrome b gene, and restriction analysis of polymerase chain reaction products
      in semipreserves.
AB  - A method of authenticating anchovy (Engraulis encrasicholus L.) and gilt sardine
      (Sardinella aurita) semipreserves (salt-cured and fillets in oil) has been
      developed by polymerase chain reaction (PCR) followed by sequence and restriction
      site analysis. The amplification of a fragment of the cytochrome b gene by
      universal primers produced a 376 base pairs (bp) fragment in all samples
      analyzed. Digestion of PCR products with XhoI, TaqI, AluI, and HinfI
      endonucleases yielded species-specific profiles distinguishing anchovy from gilt
      sardine. Therefore, the restriction length fragment polymorphism (RLFP) technique
      can be used to determine the species identity of anchovy and gilt sardine in
      semipreserves.

PMID- 11312835
TI  - Analysis of canthaxanthin and related pigments from Gordonia jacobaea mutants.
AB  - A collection of 43 mutant strains of the bacterium Gordonia jacobaea was obtained
      by means of ethyl methanesulfonate treatment, and the strains were selected for
      their different pigmentation with respect to the wild-type strain. None of the
      mutants showed auxotrophy. They all showed good genetic stability and a growth
      rate similar to that of the parental strain. Canthaxanthin and other carotenoids
      from these mutants were extracted with acetone and ethanol and separated by high
      performance liquid chromatography (HPLC). These HPLC analyses, together with
      spectrophotometric detection at 480 nm, revealed variations in the pigment
      contents of the different mutant strains.

PMID- 11312836
TI  - Optimized synthesis of lipase-catalyzed hexyl acetate in n-hexane by response
      surface methodology.
AB  - Hexyl acetate, a short-chain ester with fruity odor, is a significant green note
      flavor compound and widely used in the food industry. The ability for immobilized
      lipase from Mucor miehei (Lipozyme IM-77) to catalyze the transesterification of
      hexanol with triacetin was investigated in this study. Response surface
      methodology and five-level-five-factor central composite rotatable design were
      adopted to evaluate the effects of synthesis variables, such as reaction time (2
      10 h), temperature (25-65 degrees C), enzyme amount (10-50%; 0.024-0.118 BAUN),
      substrate molar ratio of triacetin to hexanol (1:1 to 3:1), and added water
      content (0-20%) on percentage molar conversion of hexyl acetate. The results
      showed that reaction temperature and substrate molar ratio were the most
      important parameters and that added water content had less of an effect on
      percent molar conversion. On the basis of canonical analysis, optimum synthesis
      conditions were as follows: reaction time, 7.7 h; temperature, 52.6 degrees C;
      enzyme amount, 37.1% (0.089 BAUN); substrate molar ratio, 2.7:1; and added water,
      12.5%. The predicted value was 88.9% molar conversion, and the actual
      experimental value was 86.6% molar conversion.

PMID- 11312837
TI  - Production process for high-quality pea-protein isolate with low content of
      oligosaccharides and phytate.
AB  - A process for pea-protein isolate production, resulting in low content of phytate
      and oligosaccharides, has been developed. Oligosaccharides were removed from the
      protein fraction through ultrafiltration. Ultrafiltration of 50- and 100-kD
      molecular-weight cutoffs (MWCOs) were tested, and both effectively separated the
      oligosaccharides from the protein. Phytate degradation was achieved by incubation
      of the pea-protein solution by addition of exogenous phytase enzyme. An almost
      complete degradation of inositol hexa-, penta-, tetra-, and triphosphates was
      reached using an incubation time of 1 h. The reduced content of oligosaccharides
      and inositol phosphates is likely to result in reduced flatulence and improved
      mineral bioavailability. These qualities of the pea-protein isolate make it a
      suitable protein source for infant formula production.

PMID- 11312838
TI  - Color and stability of pigments derived from the acetaldehyde-mediated
      condensation between malvidin 3-O-glucoside and (+)-catechin.
AB  - A pigment derived from the acetaldehyde-mediated condensation between (+)
      catechin and malvidin 3-O-glucoside has been prepared and isolated by
      semipreparative HPLC, and its characteristics of color and stability have been
      studied and compared with that of malvidin glucoside in aqueous solutions. When
      the pH was increased from 2.2 to 5.5, the solution of the pigment became
      progressively more violet (lambda(max) = 560 nm at pH 5.5), whereas similar
      solutions of the anthocyanin were almost colorless at pH 4.0. This behavior
      indicated that the anthocyanin moiety of the pigment was more protected against
      water attack, and thus the formation of its quinonoidal forms was favored. The
      color of the pigment also showed more stability with regard to bleaching by SO(2)
      than that of malvidin glucoside. Nevertheless, the pigment was more sensitive to
      degradation in aqueous solution than the anthocyanin. The cleavage of the ethyl
      bridge that links the anthocyanin and the catechin constituted the first step in
      its degradation, as demonstrated by the formation of malvidin glucoside as a
      major product.

PMID- 11312839
TI  - Effect of enzyme treatment during mechanical extraction of olive oil on phenolic
      compounds and polysaccharides.
AB  - The effect of the use of cell-wall-degrading-enzyme preparations during the
      mechanical extraction process of virgin olive oil on the phenolic compounds and
      polysaccharides was investigated. The use of the enzyme preparations increased
      the concentration of phenolic compounds in the paste, oil, and byproducts.
      Especially, the contents of secoiridiod derivatives such as the dialdehydic form
      of elenolic acid linked to 3,4-dihydroxyphenylethanol (3,4-DHPEA-EDA) and an
      isomer of oleuropein aglycon (3,4-DHPEA-EA), which have high antioxidant
      activities, increased significantly in the olive oil. Furthermore, the use of an
      N(2) flush during processing strongly increased the phenolic concentration.
      Analyses of the pectic polymers present in the paste showed that the use of
      pectinolytic enzyme preparations increased the yield of the buffer soluble
      pectins and the proportion of molecules with a lower molecular mass. Also, the
      content of uronic acids in the buffer soluble extract increased considerably due
      to the use of the enzyme preparations. Analysis of the polymeric carbohydrates in
      the vegetation waters showed the presence of mainly pectic polymers. The addition
      of commercial enzyme preparations increased the uronic acid content of the
      polysaccharides in the vegetation water substantially compared to the blank. This
      study showed that the addition of cell-wall-degrading enzymes did improve the
      olive oil quality; however, mechanisms remained unclear.

PMID- 11312840
TI  - In vitro test for the effectiveness of antioxidants as inhibitors of thiyl
      radical-induced reactions with unsaturated fatty acids.
AB  - Attacks of thiyl radicals on the double bonds of unsaturated fatty acids lead to
      stereomutation (cis-, trans-isomerization without double-bond migration) and
      addition reactions (thioether formation). On the basis of these findings, an in
      vitro test system has been developed which allows the study of the effectiveness
      of specific antioxidants in preventing thiyl radical-induced attacks on
      unsaturated fatty acids. The test involves thermal treatment of a mixture of
      oleic (cis-9-octadecenoic) acid and 1-tetradecanethiol with the antioxidant,
      followed by measurement of the extent of formation of the products of
      stereomutation and addition (i.e., elaidic (trans-9-octadecenoic) acid and
      isomeric 9(10)-S-tetradecylstearic acids, respectively) by gas chromatography of
      their methyl esters as a function of antioxidant concentration. Antioxidants such
      as octyl gallate, ascorbic acid 6-O-palmitate, ubiquinone 50 (coenzyme Q(10)),
      rac-alpha-tocopherol, and 2,6-di-tert-butyl-4-methylphenol (BHT) were tested for
      their ability to protect the >C=C< double bond of oleic acid against attacks of
      thiyl radicals generated from 1-tetradecanethiol by heating. The results show
      that octyl gallate, ascorbic acid 6-O-palmitate and, to some extent, ubiquinone
      50 (coenzyme Q(10)) were highly effective in preventing reactions of free thiyl
      radicals with oleic acid, whereas rac-alpha-tocopherol and BHT were moderately
      effective.

PMID- 11312841
TI  - Tagetolone and tagetenolone: two phytotoxic polyketides from Alternaria tagetica.
AB  - Two new phytotoxic polyketides, tagetolone (1) and tagetenolone (2), in addition
      to tyrosol and p-hydroxybenzoic acid, have been isolated from the organic crude
      extract of culture filtrates from the fungal pathogen Alternaria tagetica.
      Complete characterization of all structures was carried out following a careful
      analysis of their spectroscopic data (IR, MS, (1)H and (13)C NMR, and 2D NMR
      experiments).

PMID- 11312842
TI  - Determination of cutin-bound residues of chlorothalonil by immunoassay.
AB  - An indirect competitive enzyme-linked immunosorbent assay (ELISA) was used to
      determine photochemically cutin-bound residues of chlorothalonil in enzymatically
      isolated tomato and apple fruit cuticles. The samples were spiked, irradiated,
      exhaustively extracted, and depolymerized with boron trifluoride complex
      resulting in a soluble depolymerisate. With this procedure, the ELISA could be
      calibrated with free target molecules for the quantification of originally bound
      chlorothalonil residues. In fruit cuticles that were irradiated for 8 h by
      simulated sunlight, 0.030 and 0.068 mg/g photoinduced cutin-bound residues of wax
      free cuticles (calculated as chlorothalonil) were determined for tomatoes and
      apples, respectively. For the used antibody mAb chl. 4/11, cross-reactivities
      with derivatives of chlorothalonil simulating different types of cuticle-bound
      residues are given and discussed.

PMID- 11312843
TI  - Fate of postharvest-applied dichlorvos in stored and processed dates.
AB  - The fate of dichlorvos (DDVP) on dates after storage and processing of
      postharvest-treated fruits has been investigated. Residues were determined using
      GC-ECD after extraction of the fruits. A postharvest application was made to
      fruits at different stages of maturity: khalal fruits (mature full colored
      stage), rutab fruits (soft brown stage), and the mature tamer fruits (hard raisin
      like stage). The fate of the residues was followed during the storage at
      refrigerated, room, and summer average temperatures (3, 22, and 43 degrees C).
      The amount of residues absorbed varied with the level of maturity. The rate of
      the loss of the residues was found to follow first-order kinetics. First-order
      rate constants were calculated for the different levels of maturity. The rate of
      the loss of DDVP increased as the temperature of storage increased. Also, it
      decreased with increasing maturation of the dates, which was characterized by a
      decrease in moisture content as well as water activity and an increase in sugar
      content. The period of storage study was limited by the time of maturation to the
      next stage. Most common home-cooking methods, including dehydration, jam-making,
      and syrup-making, resulted in significant decreases in residue levels. Only 0-13%
      of initial DDVP residues was detected in final products.

PMID- 11312844
TI  - Association of ethylene dibromide (EDB) with mature cranberry (Vaccinium
      macrocarpon) fruit.
AB  - Ethylene dibromide (EDB), a potential carcinogen, has been used in gasoline
      mixtures to avoid the accumulation of metallic lead in engines. Ethylene
      dibromide is present in the environment and in groundwater. Previous analysis has
      shown that EDB levels have reached up to 16 microg L-1 in the groundwater at two
      fuel spill plumes in the vicinity of the Massachusetts Military Reservation (MMR)
      Base and up to 1.69 microg L-1 in the Coonamessett and Quashnet Rivers in Cape
      Cod, MA (U.S. Air Force IRP, Fact Sheet #98-10, 1998). Groundwater and river
      water from this area are used to flood some local cranberry bogs for irrigation
      and harvesting of cranberry fruits. The potential sorption of EDB by cranberry
      fruits during harvest has caused concern but information regarding its occurrence
      is not available. In this study, low levels of EDB (0.04-0.15 microg kg-1) were
      found to be associated with cranberry fruits that were exposed to EDB at levels
      ranging from 3 to 12 microg L-1 at 10, 20, and 30 degrees C for up to 7 days.
      Rinsing EDB-exposed cranberry fruits twice with deionized water or once with 0.01
      M NaCl solution reduced the amount of EDB associated with the cranberry fruits by
      65-72% to a level of 0.02 microg kg-1. Therefore, the EDB most likely is
      associated with the water residue on the surface of the cranberry fruit rather
      than being absorbed into the flesh of the fruit during the EDB exposure.

PMID- 11312845
TI  - Characteristics and composition of watermelon, pumpkin, and paprika seed oils and
      flours.
AB  - The nutritional quality and functional properties of paprika seed flour and seed
      kernel flours of pumpkin and watermelon were studied, as were the characteristics
      and structure of their seed oils. Paprika seed and seed kernels of pumpkin and
      watermelon were rich in oil and protein. All flour samples contained considerable
      amounts of P, K, Mg, Mn, and Ca. Paprika seed flour was superior to watermelon
      and pumpkin seed kernel flours in content of lysine and total essential amino
      acids. Oil samples had high amounts of unsaturated fatty acids with linoleic and
      oleic acids as the major acids. All oil samples fractionated into seven classes
      including triglycerides as a major lipid class. Data obtained for the oils'
      characteristics compare well with those of other edible oils. Antinutritional
      compounds such as stachyose, raffinose, verbascose, trypsin inhibitor, phytic
      acid, and tannins were detected in all flours. Pumpkin seed kernel flour had
      higher values of chemical score, essential amino acid index, and in vitro protein
      digestibility than the other flours examined. The first limiting amino acid was
      lysine for both watermelon and pumpkin seed kernel flours, but it was leucine in
      paprika seed flour. Protein solubility index, water and fat absorption
      capacities, emulsification properties, and foam stability were excellent in
      watermelon and pumpkin seed kernel flours and fairly good in paprika seed flour.
      Flour samples could be potentially added to food systems such as bakery products
      and ground meat formulations not only as a nutrient supplement but also as a
      functional agent in these formulations.

PMID- 11312846
TI  - Gas chromatographic analysis of total fatty acids in cider.
AB  - This paper reports the composition of total fatty acids in an apple beverage,
      cider. Fatty acids are present in the free or esterified form and contribute to
      both the flavor and foam properties of cider. Fatty acids were separated and
      identified as methyl esters by GC-MS, and 12 of these were subsequently
      determined by GC-FID. The major fatty acids found in cider were caproic,
      caprylic, capric, and palmitic acid, the saturated acids predominating over the
      unsaturated ones. The proposed method was applied to 59 ciders from three
      consecutive harvests (1996, 1997, and 1998), which were made by 19 cider-makers
      from the region of Asturias (Spain). Linear discriminant analysis of fatty acids
      in these samples allowed selection of palmitoleic, pentadecanoic, linoleic,
      myristic, and linolenic acid as the most predictive variables to differentiate
      ciders made from apples grown in the Asturias region (1997 harvest) and ciders
      made from apples grown outside this region (1996 and 1998 harvests).

PMID- 11312847
TI  - Determination of conjugated linoleic acid (CLA) concentrations in milk chocolate.
AB  - The fatty acids from a series of milk-chocolate-based confectionery samples were
      analyzed as methyl esters by GC to determine the presence and amount of
      conjugated linoleic acid (CLA). A single peak corresponding to the 9-cis,11-trans
      isomer and ranging from less than 0.1% to nearly 0.2% of the total fatty acids,
      corresponding to up to 0.3 mg per g of chocolate, was observed. One of the
      chocolate extracts and a milk extract were subjected to silver ion HPLC and GC-MS
      in order to confirm the identity of the major isomer and tentatively identity
      minor isomers.

PMID- 11312848
TI  - Analysis and properties of arabinoxylans from discrete corn wet-milling fiber
      fractions.
AB  - Three fibrous corn wet-milling fractions, coarse fiber, fine fiber, and spent
      flake, were isolated. More highly valued uses are sought for these milling
      products, which are generally directed into the corn gluten feed product stream.
      Coarse fiber was further dissected into pericarp and aleurone layers. An alkaline
      hydrogen peroxide process was used to efficiently extract corn fiber gum (CFG)
      from each of the materials. CFG is a hemicellulose B arabinoxylan which also
      contains low levels of D,L-galactose and D-glucuronic acid. CFG yield information
      was obtained from each source, as well as structural information in terms of
      degrees of branching of the beta-D-xylopyranose backbone with alpha-L
      arabinofuranosyl moieties. There were significant differences in degree of
      branching among the CFGs from the various fractions. A novel capillary
      electrophoresis procedure was developed to measure these differences. Solution
      viscosity differences among the CFGs were also observed.

PMID- 11312849
TI  - Identification of procyanidins and anthocyanins in blueberries and cranberries
      (Vaccinium spp.) using high-performance liquid chromatography/mass spectrometry.
AB  - Blueberries and cranberries were analyzed for procyanidins using normal-phase
      HPLC/MS. Monomers, identified as (+)-catechin and (-)-epicatechin, and a series
      of oligomers were detected in blueberries, and MS data confirmed that the
      oligomers consisted of (epi)catechin units that were exclusively singly linked (B
      type). The procyanidin "fingerprints" were similar for Tifblue and Rubel but
      higher than that for lowbush blueberries. In whole cranberries, (-)-epicatechin
      was present, along with a complex series of oligomers. Both A-type (contained
      only one double linkage per oligomer) and B-type oligomers were present. Two
      commercial cranberry juices exhibited similar procyanidin profiles, except that
      one contained increased quantities. There were processing effects on the
      procyanidin content of cranberry extract and juices when compared to those of the
      unprocessed fruits. Monomer, dimers, and A-type trimers were the primary
      procyanidins, with only trace levels of the B-type trimers and A-type tetramers
      and with an absence of the higher oligomers in cranberry extract and juices.

PMID- 11312851
TI  - A quantitative stable-isotope LC-MS method for the determination of folic acid in
      fortified foods.
AB  - A stable-isotope liquid chromatography-mass spectrometry (LC-MS) assay was
      developed for the quantitative determination of folic acid in fortified foods.
      Folic acid was extracted from food samples into a phosphate buffer, purified on a
      C-18 Sep-Pak cartridge, and analyzed by LC-MS in the negative ion mode using
      electrospray ionization. The analyte was quantified using (13)C(5)-folic acid as
      an internal standard. The coefficient of variation for the precision of the
      method was 5.6% based on the analysis of four sample replicates. The accuracy of
      the method was assessed using a standard method of addition of folic acid to a
      shredded whole-wheat cereal. The quantitative determination of folic acid in this
      matrix was linear over 1 order of magnitude having a concentration range of 2.4
      to 24 microg/g of food (or 0.05 to 0.5 microg of analyte injected into the LC
      MS). The overall quantitative efficiency of the method was evaluated using a
      standard reference material (infant formula SRM 1846). The method was applied to
      the determination of folic acid in several test samples (fortified breakfast
      cereals), and the values were in accord with the manufacturer's claim. This
      method advances a LC-MS technique for the determination of folic acid in
      fortified foods based on stable-isotope dilution methodology. The specificity of
      the technique and quantitative accuracy of the method in various food substrates
      suggests that the method may be adapted for routine analysis in other fortified
      foods.

PMID- 11312850
TI  - Composition of pecan cultivars Wichita and Western Schley [Carya illinoinensis
      (Wangenh.)K. Koch] grown in Australia.
AB  - Pecans from the cultivars Wichita and Western Schley [Carya illinoinensis
      (Wangenh.) K. Koch] collected over three years were analyzed for the following
      constituents: total lipid content; fatty acid profiles; sucrose content; protein;
      total dietary fiber; the minerals magnesium, calcium, potassium, sulfur,
      phosphorus, boron, copper, iron, manganese, sodium, zinc, and aluminum; vitamin
      C; and lipase and lipoxygenase activities. Year of harvest and cultivar had
      little effect on the composition of the pecans. Overall, protein content was the
      only constituent that differed between pecans grown in Australia and those grown
      in the United States. This difference is probably related to differences in
      growing location and horticultural practices between the two countries.

PMID- 11312852
TI  - Preparation of pentachlorophenol derivatives and development of a microparticle
      based on-site immunoassay for the detection of PCP in soil samples.
AB  - Pentachlorophenol (PCP) is used as a herbicide in agriculture and as an
      insecticide for termite control. Because of the apparent hazard associated with
      its usage, there is a need for an efficient and economic on-site screening
      method. A 5-min on-site test has been developed for the detection of PCP based on
      the OnTrak format, a successful Roche on-site test format for drugs of abuse,
      utilizing the principle of latex agglutination immunoassay. The test detects 1
      ppm of PCP in soil samples.

PMID- 11312853
TI  - Fate of a phenylpyrazole in vegetation and soil under tropical field conditions.
AB  - The fate of fipronil, a phenylpyrazole insecticide, and its metabolites under
      tropical conditions was studied in soil and in vegetation after treatment for
      locust control. Two different plots were treated with a formulation of fipronil
      at doses of 5 and 10 g of active ingredient ha(-)(1), respectively. Vegetation
      and soil at depths of 0-5 and 5-20 cm were sampled for up to 2 months after
      treatment. After extraction and purification on fipronil immunoaffinity
      cartridges, residues were analyzed by gas chromatography using electron capture
      and mass detectors. In soil, a rapid initial decrease of fipronil was observed
      with a rapid formation of the sulfone and the photodegradate; the amide and the
      sulfide were not detected. In vegetation, a rapid initial decrease of fipronil
      was also observed with a rapid formation of mostly the sulfone; the
      photodegradate and the sulfide were also detected but at much lower
      concentrations. The metabolites resulting from the degradation of fipronil were
      similar in both soil and vegetation, but their relative concentrations were
      different.

PMID- 11312854
TI  - Controlled release of manganese into water from coated experimental fertilizers:
      laboratory characterization.
AB  - The release of manganese into water from controlled-release formulations
      containing manganese EDTA or manganese lignosulfonate was studied. These
      fertilizers were obtained in the laboratory by adhering the source of manganese
      over urea pellets and by adding a coating. The materials used as adhesives and
      coatings were mixtures of rosins plus tricalcium phosphate. With regard to the
      chemical composition, these formulations conformed to national and international
      standards for commercial fertilizers. The rate of release of manganese was a
      function of both the source of manganese used and the coating thickness. Under
      the same conditions the release of manganese was greater for formulations with
      manganese EDTA than with manganese lignosulfonate. To predict the kinetic
      behaviors of the two series of formulations, mathematical equations were
      established. The manganese source plus rosin coatings improved the handling and
      storage characteristics of the commercial urea pellets. The study of the rosin
      coatings using scanning electron microscopy showed that they were compact and
      homogeneous.

PMID- 11312855
TI  - The formation of 2-chlorobenzamide upon hydrolysis of the benzoylphenylurea
      insecticide 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea in different water
      systems.
AB  - It has been reported that 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea (CCU), an
      insect growth regulator, has no measurable toxicity to nontarget organisms and is
      essentially harmless to humans. However, one of its degradation products, 2
      chlorobenzamide (CBA), is suspected of being a carcinogen. Therefore, the maximum
      concentration of CBA formed and the dynamics of its formation need to be given
      careful attention after CCU is used in the field. This paper describes the
      degradation of CCU to form CBA in three different water systems (distilled water,
      spring water, and simulated seawater) and the effects of temperature on the
      dynamics of CBA formation. The results indicate that the maximum level of CBA
      concentration is different in the different systems (highest in spring water) and
      that the temperature has a significant impact on the process (higher temperature
      leads to higher and earlier peak of CBA concentration). The maximum concentration
      of CBA after application of CCU was approximately 3.8% of the initial
      concentration of CCU at 35 degrees C in distilled water, and 2.4% in spring water
      at 25 degrees C.

PMID- 11312856
TI  - Efficiency of rice bran for removal of organochlorine compounds and benzene from
      industrial wastewater.
AB  - Rice bran was found to effectively adsorb several organic compounds, such as
      dichloromethane, chloroform, carbon tetrachloride, trichloroethylene,
      tetrachloroethylene, and benzene. Equilibrium adsorption isotherms conformed to
      the Freundlich type (log-log linear). The adsorption of dichloromethane and
      chloroform by rice bran was observed over the range of pH 1-11. Therefore, rice
      bran is applicable for treatment of wastewater over a wide pH range.
      Dichloromethane was successfully removed from water samples with an average
      removal efficiency of 70% after 60 min when rice bran was added to water samples
      containing from 0.006 to 100 mg/L dichloromethane. The removal of these
      organochlorine compounds and benzene by rice bran was attributed to the uptake by
      intracellular particles called spherosomes. Here, we report the results of a
      fundamental study of the efficiency of rice bran for removal of organochlorine
      compounds and benzene using a batch system on the laboratory scale, and describe
      elucidation of the mechanism of removal of these compounds by rice bran.

PMID- 11312857
TI  - Role of ferrihydrite in adsorption of three imidazolinone herbicides.
AB  - Adsorption of the imidazolinone herbicides imazapyr, imazethapyr, and imazaquin
      on synthetic ferrihydrites, either freeze-dried or not-freeze-dried, has been
      studied. The synthetic ferrihydrites were characterized by X-ray diffraction,
      scanning electron micrographs, and specific area determination. On each
      ferrihydrite, adsorption was found to be strongly dependent on pH. The highest
      extent of adsorption took place at pH values close to the pK(a) of the carboxylic
      group of the herbicides. No adsorption was observed at pH > 8. The freeze-drying
      process reduced the adsorptive capacity of the ferrihydrite by formation of
      larger aggregates provoking a decrease of the surface area. The chemical
      differences between the herbicides did not strongly affect the adsorption process
      of the herbicides. However, imazaquin was more adsorbed than the other two
      herbicides, in particular at pH close to its pK(a).

PMID- 11312858
TI  - Evaluation of the representativeness of the odor of cooked mussel extracts and
      the relationship between sensory descriptors and potent odorants.
AB  - The representativeness of the odor of mussel extract was assessed after each step
      of the distillation-extraction-concentration process. Results showed that the
      whole process was convenient for cooked mussels, but the extract was
      representative only when it was reincorporated into a suitable matrix such as
      water. Sensory and gas chromatography-olfactometry (GC-O) analyses were then
      performed on representative extracts of wild and bouchot mussels. Most of the
      sensory attributes were related to odors detected during olfactometry. Methional
      and (Z)-4-heptenal were two of the most potent odorants of mussels and, thus,
      were identified as the major contributors to the characteristic boiled potato
      like odor of cooked mussels distinguished during sensory analysis. The sulfury
      note, highlighted for wild mussels during sensory analysis, could be linked to
      dimethyl disulfide, which was significantly more perceived in wild mussels by GC
      O. Dimethyl disulfide could then be considered to be a characteristic compound of
      wild mussels.

PMID- 11312859
TI  - Volatile constituents of Chinese chive (Allium tuberosum Rottl. ex Sprengel) and
      rakkyo (Allium chinense G. Don).
AB  - Volatile components were isolated from Chinese chive and rakkyo by simultaneous
      steam distillation-solvent extraction and analyzed by GC and GC-MS. Sulfur
      compounds account for 88 and 94% of the total volatiles in the isolated extract
      of Chinese chive and rakkyo, respectively. In addition to the sulfur compounds
      commonly reported in the genus Allium, 27 novel volatile sulfur-containing
      components were found in the isolated extracts of both species. Among them were a
      sulfide, disulfides, trisulfides, and tetrasulfides with ethyl, butyl, and pentyl
      groups.

PMID- 11312860
TI  - Light reflected from colored mulches affects aroma and phenol content of sweet
      basil (Ocimum basilicum L.) leaves.
AB  - Basil (Ocimum basilicum L.) is an herb the leaves of which are used to add a
      distinct aroma and flavor to food. It was hypothesized that the size and chemical
      composition of sun-grown basil leaves could be influenced by the color of light
      reflected from the soil surface and by the action of the reflected light through
      the natural growth regulatory system within the growing plants. Leaf morphology,
      aroma compounds, and soluble phenolics were compared in basil that had been grown
      over six colors of polyethylene row covers. Altering the ratios of blue, red, and
      far-red light reflected to growing plants influenced both leaf morphology and
      chemistry. Leaves developing over red surfaces had greater area, moisture
      percentage (succulence), and fresh weight than those developing over black
      surfaces. Basil grown over yellow and green surfaces produced significantly
      higher concentrations of aroma compounds than did basil grown over white and blue
      covers. Leaves grown over yellow and green mulches also contained significantly
      higher concentrations of phenolics than those grown over the other colors.
      Clearly, the wavelengths (color) of light reflected to growing basil plants
      affected leaf size, aroma, and concentrations of soluble phenolics, some of which
      are antioxidants.

PMID- 11312861
TI  - Characterization of natural "cooling" compounds formed from glucose and l-proline
      in dark malt by application of taste dilution analysis.
AB  - Gel permeation chromatography of the solvent extractables isolated from a
      thermally treated glucose/L-proline mixture and sensory analysis of the fractions
      collected led to the discovery of the presence of "cooling" compounds in Maillard
      reactions. To characterize the key compounds imparting this cooling sensation to
      the oral cavity, a taste dilution analysis was performed by determining the taste
      threshold of reaction products in serial dilutions of HPLC fractions to select
      the most intense "cooling" compounds in the complex GPC fraction of the Maillard
      reaction mixture. Systematic (13)C-labeling experiments and GC-MS, LC-MS, and 1D-
      and 2D-NMR measurements, followed by synthesis, led to the unequivocal
      identification of 3-methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one (3-MPC), 5
      methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one (5-MPC), and 2,5-dimethyl-4-(1
      pyrrolidinyl)-3(2H)-furanone (DMPF) as the key compounds contributing the most to
      the cooling sensation. Although these structures were described earlier with
      regard to Maillard reactions, this is the first time that Maillard reaction
      products are reported to cause intense cooling sensations by degustation.
      Finally, the detection of 5-MPC (101.3 microg/kg), 3-MPC (9.4 microg/kg), and
      DMPF (11.5 microg/kg) in dark malt verified their natural occurrence in thermally
      processed foods.

PMID- 11312862
TI  - Identification of volatile compounds in cantaloupe at various developmental
      stages using solid phase microextraction.
AB  - Using an automated rapid headspace solid phase microextraction (SPME) method for
      volatile extraction in cantaloupes, 86 compounds already reported for muskmelons
      were recovered and an additional 53 compounds not previously reported were
      identified or tentatively identified. The SPME method extracted a copious number
      of volatiles that can be analyzed to clearly differentiate between variety,
      growth stage, and stage of harvest ripeness. Most of the newly reported compounds
      in cantaloupe were esters and aldehydes that have already been demonstrated as
      flavor-related compounds in other products. All esters believed to have flavor
      impact increased progressively after pollination, and this trend continued with
      increasing harvest maturity. However, compound recovery often decreased when
      fruits were harvested over-ripe. Most aldehydes increased during early growth
      stages and then tapered off with increasing harvest maturity. The SPME method
      suitably recovered most compounds reported to impart characteristic flavor/aroma
      in muskmelons. SPME offers experimental flexibility and the ability to discover
      more compounds and address flavor quality changes in fresh-cut cantaloupe.

PMID- 11312863
TI  - Formation by mechanical stimulus of the flavor compounds in young leaves of
      Japanese pepper (Xanthoxylum piperitum DC.).
AB  - The volatile compounds formed in slapped and crushed young leaves of Japanese
      pepper (Xanthoxylum piperitum DC.) were compared with those of intact leaves by
      using a dynamic headspace gas analysis combined with GC-MS in an on-line system,
      together with the results of a sensory evaluation. The results indicated that the
      factors influencing the aroma note were mainly the constituent oxygenated
      monoterpenes and C(6) compounds and the quantity of terpene hydrocarbons. To
      clarify the formation mechanism for the aroma, the activities of lipoxygenase and
      beta-D-glucosidase were investigated. The results revealed that the hydrolysis of
      glycosides and the degradation of unsaturated fatty acids both played an
      important role in the formation of the major aroma compounds in young leaves of
      Japanese pepper.

PMID- 11312864
TI  - Evaluation of key aroma compounds in hand-squeezed grapefruit juice (Citrus
      paradisi Macfayden) by quantitation and flavor reconstitution experiments.
AB  - Twenty-five odor-active compounds were quantified in the fresh, hand-squeezed
      juice of White Marsh seedless grapefruits using stable isotope dilution assays.
      By calculation of the odor activity values of the odorants (ratio of their
      concentrations in the juice to their odor thresholds in water) it was shown that
      the fruity esters ethyl 2-methylpropanoate, ethyl butanoate, and (S)-ethyl 2
      methylbutanoate, and the fruity, sweet winelactone, as well as the grassy
      smelling (Z)-hex-3-enal, and trans-4,5-epoxy-(E)-dec-2-enal with metallic odor,
      were among the most potent odorants of the fresh grapefruit juice. The typical
      sulfurous, grapefruit-like odor quality was mainly due to the catty, blackcurrant
      like 4-mercapto-4-methylpentan-2-one and the grapefruit-like smelling 1-p
      menthene-8-thiol. These findings were confirmed by reconstitution experiments to
      simulate the aroma of the fresh grapefruit juice.

PMID- 11312865
TI  - Optimizing headspace temperature and time sampling for identification of volatile
      compounds in ground roasted Arabica coffee.
AB  - Equilibration time and temperature were the factors studied to choose the best
      conditions for analyzing volatiles in roasted ground Arabica coffee by a static
      headspace sampling extraction method. Three temperatures of equilibration were
      studied: 60, 80, and 90 degrees C. A larger quantity of volatile compounds was
      extracted at 90 degrees C than at 80 or 60 degrees C, although the same
      qualitative profile was found for each. The extraction of the volatile compounds
      was studied at seven different equilibration times: 30, 45, 60, 80, 100, 120, and
      150 min. The best time of equilibration for headspace analysis of roasted ground
      Arabica coffee should be selected depending on the chemical class or compound
      studied. One hundred and twenty-two volatile compounds were identified, including
      26 furans, 20 ketones, 20 pyrazines, 9 alcohols, 9 aldehydes, 8 esters, 6
      pyrroles, 6 thiophenes, 4 sulfur compounds, 3 benzenic compounds, 2 phenolic
      compounds, 2 pyridines, 2 thiazoles, 1 oxazole, 1 lactone, 1 alkane, 1 alkene,
      and 1 acid.

PMID- 11312866
TI  - Evidence of starch inclusion complexation with lactones.
AB  - Starch, in particular the linear amylose, is able to form inclusion complexes
      with a wide spectrum of ligand molecules, among them flavor compounds. The
      complexing ability of a homologous series of gamma- and delta-lactones with
      potato starch was followed by amperometric iodine titration, differential
      scanning calorimetry, and wide-angle X-ray diffraction measurements. Lactones
      with a linear chain of a size > or = C(5) form inclusion complexes with starch,
      whereas lactones with a short linear chain, such as gamma-heptalactone, show poor
      complexing ability. The thermal stability of starch-lactone complexes increases
      with increasing chain length of the lactone. In general, lactones induce the
      formation of V(h) helices. Only delta-decalactone complexes with starch were not
      definitely identified as V(h) amylose helices. Complexation of starch dispersions
      with lactones induce turbidity and gelation or phase separation, both phenomena
      being the result of microphase separation.

PMID- 11312867
TI  - Flavor threshold for acetaldehyde in milk, chocolate milk, and spring water using
      solid phase microextraction gas chromatography for quantification.
AB  - The detection threshold of acetaldehyde was determined on whole, lowfat, and
      nonfat milks, chocolate-flavored milk, and spring water. Knowledge of the
      acetaldehyde threshold is important because acetaldehyde forms in milk during
      storage as a result of light oxidation. It is also a degradation product of
      poly(ethylene terephthalate) during melt processing, a relatively new packaging
      choice for milk and water. There was no significant difference in the
      acetaldehyde threshold in milk of various fat contents, with thresholds ranging
      from 3939 to 4040 ppb. Chocolate-flavored milk and spring water showed thresholds
      of 10048 and 167 ppb, respectively, which compares favorably with previous
      studies. Solid phase microextraction (SPME) was verified as an effective method
      for the recovery of acetaldehyde in all media with detection levels as low as 200
      and 20 ppb in milk and water, respectively, when using a polydimethyl
      siloxane/Carboxen SPME fiber in static headspace at 45 degrees C for 15 min.

PMID- 11312868
TI  - Characteristic aroma components of British Farmhouse Cheddar cheese.
AB  - Aroma components responsible for aroma typical of British Farmhouse Cheddar
      cheese were studied by aroma extract dilution analysis. Cheese extracts were
      prepared by direct solvent extraction, high-vacuum transfer, and class
      fractionation. Most aroma-active components of acidic and neutral/basic fractions
      have been previously associated with Cheddar cheese flavor. p-Cresol was mainly
      responsible for a "cowy-barny" note, whereas an intense "soil-like" note was due
      to 2-isopropyl-3-methoxypyrazine. At much lower odor intensity, 2-isobutyl-3
      methoxypyrazine contributed a "bell pepper-like" note. Additionally, within the
      same wedge of cheese, the concentrations of p-cresol and 2-isopropyl-3
      methoxypyrazine were lower at the narrow end (center) than at the rind side.
      Direct addition of p-cresol (> or =100 ppb) or 2-isopropyl-3-methoxypyrazine (>
      or =3 ppb) in a mild domestic Cheddar cheese resulted in increases in intensities
      of cowy/phenolic and earthy/bell pepper aroma notes.

PMID- 11312869
TI  - Verification of a mouth simulator by in vivo measurements.
AB  - The volatile content of the effluent from the retronasal aroma simulator (RAS)
      was compared with that of human breath using mass spectroscopy (MS-Nose). The
      ratios of volatile compounds from the RAS were closely related to those from the
      panelists' breath with the correlation coefficients ranging from 0.97 to 0.99
      from model food systems. A greater sensitivity using the RAS was achieved because
      higher concentrations of volatiles in the MS-Nose were produced from the RAS than
      from the breath. In analyzing the effects on volatility of RAS parameters
      including airflow rate, temperature, saliva ratio, and blending speed, airflow
      rate had the greatest effect. The correlation coefficients for the real food
      systems studied ranged from 0.83 to 0.99. The RAS gives a good approximation of
      time-averaged flavor release in the mouth as defined by breath-by-breath
      measurements.

PMID- 11312870
TI  - Variation of major volatile constituents in various green teas from Southeast
      Asia.
AB  - A total of 15 green tea samples were prepared from fresh tea leaves obtained from
      three different countries: two from Laos, seven from Myanmar, and six from
      Vietnam. The volatile aroma constituents of the 15 samples were analyzed by gas
      chromatography/mass spectroscopy. Eleven aroma constituents were chosen from over
      100 chemicals found in the samples to compare differences among various teas.
      They were hexanal, 1-penten-3-ol, heptanal, 1-pentenal, (Z)-2-penten-1-ol, (Z)-3
      penten-1-ol, linalool oxide (trans-furanoid), linalool oxide (cis-furanoid),
      linalool, linalyl propanoate, and geraniol. Generally, concentrations of linalool
      and hexanal seem to play an important role in the quality of green teas. Green
      teas from Laos and Myanmar contained heterocyclic compounds, such as pyridines
      and pyrazines, formed by high-temperature processing. The presence of these
      heterocyclic compounds suggested that the temperature used for tea processing
      plays an important role in the formation of aroma chemicals in green teas.

PMID- 11312871
TI  - Mechanical and barrier properties of cross-linked soy and whey protein based
      films.
AB  - Sterilized biofilms based on soy protein isolate (SPI, S system) and a 1:1
      mixture of SPI and whey protein isolate (WPI, SW system) were achieved through
      the formation of cross-links by means of gamma-irradiation combined with thermal
      treatments. The effect of the incorporation of carboxymethylcellulose (CMC) and
      poly(vinyl alcohol) was also examined. gamma-Irradiation combined with thermal
      treatment improved significantly the mechanical properties, namely, puncture
      strength and puncture deformation, for all types of films. Irradiated
      formulations that contain CMC behave more similarly as elastomers. CMC showed
      also significant improvements of the barrier properties, namely, water vapor
      permeability, for irradiated films of the S system and for non-irradiated films
      of the SW system.

PMID- 11312872
TI  - Characterization of the geographical origin of Pecorino Sardo cheese by casein
      stable isotope ((13)c/(12)c and (15)n/(14)n) ratios and free amino acid ratios.
AB  - The stable isotope ratios ((13)C/(12)C and (15)N/(14)N) of casein measured by
      isotope ratio mass spectrometry (IRMS) and some free amino acid ratios (His/Pro,
      Ile/Pro, Met/Pro, and Thr/Pro) determined by HPLC in samples of ewes' milk cheese
      from Sardinia, Sicily, and Apulia were found to be parameters independent of
      ripening time. Multivariate data treatments performed by applying both
      unsupervised (principal component analysis and cluster analysis) and supervised
      [linear discriminant analysis (LDA)] methods revealed good discrimination
      possibilities for the cheeses according to place of origin. In this respect,
      particularly significant were the variables Ile/Pro, Thr/Pro, (13)C/(12)C, and
      (15) N/(14)N ratios on which basis 100% discrimination and classification of the
      samples by LDA was obtained.

PMID- 11312873
TI  - Comparison of volatiles, phenolics, sugars, antioxidant vitamins, and sensory
      quality of different colored carrot varieties.
AB  - Four different colored carrots, orange, purple with orange core, yellow, and
      white, were examined for their content of phenolics, antioxidant vitamins, and
      sugars as well as their volatiles and sensory responses. A total of 35 volatiles
      were identified in all carrots, 27 positively. White carrot contained the highest
      content of volatiles, followed by orange, purple, and yellow. In total, 11, 16,
      10, and 9 phenolic compounds were determined for the first time in orange,
      purple, yellow, and white carrots, respectively. Of these, chlorogenic acid was
      the most predominant phenolic compound in all carrot varieties. Differences (p <
      0.05) in relative sweetness, the contents of vitamin C and alpha- and beta
      carotenes, and certain flavor characteristics were observed among the colored
      carrot varieties examined. Purple carrots contained 2.2 and 2.3 times more alpha-
      and beta-carotenes (trace in yellow; not detected in white) than orange carrots,
      respectively. Purple carrot may be used in place of other carrot varieties to
      take advantage of its nutraceutical components.

PMID- 11312874
TI  - Wine production using yeast immobilized on apple pieces at low and room
      temperatures.
AB  - A biocatalyst was prepared by immobilization of Saccharomyces cerevisiae strain
      AXAZ-1 on apple pieces. It was examined by electron microscope and studied during
      the fermentation of grape must for batch wine-making. The immobilized yeast
      showed an important operational stability without any decrease of its activity
      even at low temperatures (1-12 degrees C). Specifically, at 6 degrees C the
      biocatalyst favored wine production within 8 days, which is less time than is
      required for the natural fermentation of grape must. At 1 degrees C wine
      production was effected in 1 month. This speeding up of the fermentation could be
      accepted and adopted by the industry for scaling up the wine-making process.
      Total and volatile acidities were similar to those found in dry wines. The
      concentrations of higher alcohols (propanol-1 and isobutyl alcohol) were low. The
      presence of amyl alcohols proved to be temperature dependent and decreased with
      the temperature decrease. The values of ethyl acetate concentrations were
      relatively high, up to 154 mg/L. This probably contributes to the fruity aroma
      and excellent taste of the produced wines. There was no indication of vinegar
      odor in the product given that the volatile acidity was <0.47 g of acetic acid/L.
      From the GC-MS analysis it was concluded that cell immobilization did not create
      serious changes in the product (wine) with regard to the qualitative composition
      of the aroma compounds.

PMID- 11312875
TI  - Isolation and characterization of antioxidant compounds from Aspergillus candidus
      broth filtrate.
AB  - The objectives of this study were to isolate the antioxidative components in the
      broth filtrate of Aspergillus candidus (CCRC 31543), to characterize their
      antioxidative properties, and to evaluate their safety. Three major compounds
      were isolated and identified as 3,3' '-dihydroxyterphenyllin, 3
      hydroxyterphenyllin, and candidusin B. In the linoleic acid peroxidation system,
      the inhibition of peroxidation in these three compounds was greater than 95% and
      was significantly higher than that of alpha-tocopherol but equal to that of BHA
      at 12.5-200 microg/mL. As measured using the Rancimat method in lard, 3,3' '-di
      OH-terphenyllin exhibited a protection factor value of 7.82, which was
      substantially higher than those of BHA (5.58) and alpha-tocopherol (4.29) at 200
      microg/mL. 3,3' '-di-OH-terphenyllin and 3-OH-terphenyllin also exhibited marked
      scavenging effects on the alpha,alpha-diphenyl-beta-picrylhydrazyl radicals (94.7
      and 96.0%, respectively), which were similar to those of BHA and alpha
      tocopherol. Safety studies showed that these three compounds were neither cyto-
      nor geno-toxic toward human intestine 407 (INT 407) cells, nor mutagenic toward
      Salmonella typhimurium TA98 and TA100.

PMID- 11312876
TI  - Determination of authenticity, regional origin, and vintage of Slovenian wines
      using a combination of IRMS and SNIF-NMR analyses.
AB  - The authenticity and geographical origin of wines produced in Slovenia were
      investigated by a combination of IRMS and SNIF-NMR methods. A total of 102 grape
      samples of selected wines were carefully collected in three different wine
      growing regions of Slovenia in 1996, 1997, and 1998. The stable isotope data were
      evaluated using principal component analysis (PCA) and linear discriminant
      analysis (LDA). The isotopic ratios to discriminate between coastal and
      continental regions are the deuterium/hydrogen isotopic ratio of the methylene
      site in the ethanol molecule (D/H)(II) and delta(13)C values; including also
      delta(18)O values in the PCA and LDA made possible separation between the two
      continental regions Drava and Sava. It was found that delta(18)O values are
      modified by the meteorological events during grape ripening and harvest. The
      usefulness of isotopic parameters for detecting adulteration or watering and to
      assess the geographical origin of wines is improved only when they are used
      concurrently.

PMID- 11312877
TI  - Beer consumption and changes in stability of human serum proteins.
AB  - The aim of this study was to evaluate the influence of beer consumption (BC) on
      the functional and structural properties of human serum proteins (HSP). Thirty
      eight volunteers (after coronary bypass) were divided into two groups:
      experimental (EG) and control (CG). Nineteen volunteers of the EG consumed 330 mL
      per day of beer (about 20 g of alcohol) for 30 consecutive days. The CG
      volunteers consumed mineral water instead of beer. Blood samples were collected
      from EG and CG patients before and after the experiment. Albumin (Alb), globulin
      (Glo), and methanol-precipitable proteins (MPP) from human serum were denatured
      with 8 M urea. Fluorescence and electrophoresis were employed in order to
      elucidate urea-induced conformational changes and structural behavior of
      proteins. The measured fluorescence emission spectra were used to estimate the
      stability of native and denatured protein fractions before and after BC. It was
      found that before BC the fractions most stable to urea denaturation were Glo,
      Alb, and MPP fractions. After BC in most of the beer-consuming patients (EG) some
      changes in native and denatured protein fractions were detected: a tendency to
      lower stability and minor structural deviations. These qualitative changes were
      more profound in MPP than in Alb and Glo. Thus, Glo is more resistible to alcohol
      influence than Alb, which in turn is more resistible than MPP. No serum protein
      changes were detected in patients of CG.

PMID- 11312878
TI  - Partial purification and characterization of polyphenol oxidase from banana (Musa
      sapientum L.) peel.
AB  - Polyphenol oxidase (EC 1.10.3.1, o-diphenol: oxygen oxidoreductase, PPO) of
      banana (Musa sapientum L.) peel was partially purified about 460-fold with a
      recovery of 2.2% using dopamine as substrate. The enzyme showed a single peak on
      Toyopearl HW55-S chromatography. However, two bands were detected by staining
      with Coomassie brilliant blue on PAGE: one was very clear, and the other was
      faint. Molecular weight for purified PPO was estimated to be about 41 000 by gel
      filtration. The enzyme quickly oxidized dopamine, and its Km value (Michaelis
      constant) for dopamine was 3.9 mM. Optimum pH was 6.5 and the PPO activity was
      quite stable in the range of pH 5-11 for 48 h. The enzyme had an optimum
      temperature at 30 degrees C and was stable up to 60 degrees C after heat
      treatment for 30 min. The enzyme activity was strongly inhibited by sodium
      diethyldithiocarbamate, potassium cyanide, L-ascorbic acid, and cysteine at 1 mM.
      Under a low buffer capacity, the enzyme was also strongly inhibited by citric
      acid and acetic acid at 10 mM.

PMID- 11312879
TI  - Simultaneous determination of thiamin and riboflavin in mushrooms by liquid
      chromatography.
AB  - A simple, fast, inexpensive, and reliable method useful for the simultaneous,
      routine determination of thiamin and riboflavin in mushrooms is examined. It uses
      the extraction procedure, with slight modifications, proposed by the AOAC for the
      extraction of thiamin and riboflavin, followed by a liquid chromatographic
      separation on a reversed-phase Spherisorb ODS column with methanol/water as
      mobile phase gradient. Fluorometric detection is used at the following excitation
      and emission wavelengths, respectively, 360 and 425 nm in the case of thiamin and
      422 and 515 nm for riboflavin. The analytical parameters of linearity, the
      precision of the method (RSD = 2.45 and 2.51% for thiamin and riboflavin,
      respectively), and the results of the comparison with the corresponding AOAC
      fluorometric methods show that the studied method is useful for the measurement
      of thiamin and riboflavin in fresh mushrooms.

PMID- 11312880
TI  - Antioxidant effects of water extracts from barley (Hordeum vulgare L.) prepared
      under different roasting temperatures.
AB  - The antioxidant effects of water extracts of roasted barley (WERB) were
      investigated under different roasting temperatures and compared with those of the
      water extracts of unroasted barley (WEUB). It was found that the Maillard
      reaction products increased upon increasing the roasting temperatures. Both WERB
      and WEUB exhibited significant antioxidant activities in linoleic acid and
      liposome model systems. Although WERB and WEUB afforded considerable protection
      against the damage of deoxyribose and proteins, the antioxidant efficiency of
      roasted samples was weaker than that of unroasted samples because of the
      reduction of antioxidant components (catechin, tocopherol, and lutein) with
      increasing roasting temperature. Unroasted samples were more effective in
      reducing power, quenching free radical, hydroxyl radical, and chelating iron than
      the roasted samples. The different antioxidant activity among roasted and
      unroasted barley samples may be partly attributed to the changes in catechin,
      tocopherol, and lutein contents.

PMID- 11312881
TI  - Induction of apoptosis by garcinol and curcumin through cytochrome c release and
      activation of caspases in human leukemia HL-60 cells.
AB  - Garcinol, a polyisoprenylated benzophenone, was purified from Garcinia indica
      fruit rind. The effects of garcinol and curcumin on cell viability in human
      leukemia HL-60 cells were investigated. Garcinol and curcumin displayed strong
      growth inhibitory effects against human leukemia HL-60 cells, with estimated
      IC(50) values of 9.42 and 19.5 microM, respectively. Garcinol was able to induce
      apoptosis in a concentration- and time-dependent manner; however, curcumin was
      less effective. Treatment with garcinol caused induction of caspase-3/CPP32
      activity in a dose- and time-dependent manner, but not caspase-1 activity, and
      induced the degradation of poly(ADP-ribose) polymerase (PARP). Pretreatment with
      caspase-3 inhibitor inhibited garcinol-induced DNA fragmentation. Treatment with
      garcinol (20 microM) caused a rapid loss of mitochondrial transmembrane
      potential, release of mitochondrial cytochrome c into cytosol, and subsequent
      induction of procaspase-9 processing. The cleavage of D4-GDI, an abundant
      hematopoietic cell GDP dissociation inhibitor for the Ras-related Rho family
      GTPases, occurred simultaneously with the activation of caspase-3 but preceded
      DNA fragmentation and the morphological changes associated with apoptotic cell
      death. Of these, Bcl-2, Bad, and Bax were studied. The level of expression of Bcl
      2 slightly decreased, while the levels of Bad and Bax were dramatically increased
      in cells treated with garcinol. These results indicate that garcinol allows
      caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal
      DNA and induces DFF-45 (DNA fragmentation factor) degradation. It is suggested
      that garcinol-induced apoptosis is triggered by the release of cytochrome c into
      the cytosol, procaspase-9 processing, activation of caspase-3 and caspase-2,
      degradation of PARP, and DNA fragmentation caused by the caspase-activated
      deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by
      garcinol may provide a pivotal mechanism for its cancer chemopreventive action.

PMID- 11312882
TI  - Four new steroidal saponins from the seeds of Allium tuberosum.
AB  - Four new steroidal saponins, 26-O-beta-D-glucopyranosyl-(25S,20R)-20-O-methyl
      5alpha-furost-22(23)-en-2alpha,3beta,20,26-tetraol 3-O-alpha-L-rhamnopyranosyl-(1
      ->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-glucopyranoside (1); 26-O-beta-D
      glucopyranosyl-(25S,20R)-5alpha-furost-22(23)-en-2alpha,3beta,20,26-tetraol 3-O
      alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L- rhamnopyranosyl-(1-->4)]-beta-D
      glucopyranoside (2); 26-O-beta-D-glucopyranosyl-(25S,20S)-5alpha-furost-22(23)-en
      2alpha,3beta,20,26-tetraol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-
      rhamnopyranosyl-(1-->4)]-beta-D-glucopyranoside (3); and 26-O-beta-D
      glucopyranosyl-(25S,20S)-5alpha-furost-22(23)-en-3beta,20,26-triol 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-glucopyranoside
      (4), have been isolated from the seeds of Allium tuberosum. Their structures were
      established by spectroscopic studies such as MS, IR, NMR, and 2D-NMR and the
      results of acid hydrolysis and named tuberosides F, G, H, and I, respectively.

PMID- 11312883
TI  - Resveratrol and a novel tyrosinase in Carignan grape juice.
AB  - Polyphenol levels in wines are affected by the wine-making process. Resveratrol
      is one polyphenol which has been the subject of a commendable amount of recent
      research. In this work, we found that resveratrol is immediately degraded by
      tyrosinase. A novel tyrosinase was purified from Carignan grapes. The
      purification process included salting out and separation on a cation-exchange
      column, followed by gel filtration. Tyrosinase was purified in a homogeneous form
      by SDS-PAGE and was characterized: its specific activity toward 3-(3,4
      dihydroxyphenyl)-L-alanine (DOPA) increased by a factor of 24 with an overall
      recovery of 3% of initial activity. The apparent molecular mass of the purified
      tyrosinase was 40 kDa as determined by SDS-PAGE, and 42 kDa as determined by gel
      filtration. Its activity was optimal at pH 6 and at 25 degrees C. The enzyme
      exhibited high activity toward phenylenediamine, epicatechin, pyrogallol, DOPA,
      and resveratrol. Tyrosinase activity was inhibited by KCN, thiourea, and SO(2).
      Resveratrol levels were stable following the removal of proteins from the juice,
      suggesting that early spraying of grapes with SO(2) is an important factor
      affecting the final amount of resveratrol in wine.

PMID- 11312884
TI  - Reactions of p-coumaric acid with nitrite: product isolation and mechanism
      studies.
AB  - p-Coumaric acid (1) is an abundant plant phenolic acid, a dietary
      chemoprotectant, and an antioxidant. The chemoprotective properties of 1 were
      demonstrated in vitro by its reaction with NaNO(2) in H(2)O over a range of pH
      values. The reaction pathway of 1 with nitrite is dependent on pH. 4
      Hydroxybenzaldehyde (3, 16%), 1',4-dihydroxybenzeneacetaldehyde oxime (5, 59%),
      and 4-hydroxy-1'-oxo-benzeneacetaldehyde aldoxime (7, 26%) and 7-hydroxy-1,2(4H)
      benzoxazin-4-one (11, 6%) were each formed at pH 2, whereas 4-(2-oxido-1,2,5
      oxadiazol-3-yl)phenol (13) was formed at pH 3 (6%) and pH 7 and 10 (both 1%).
      Products were isolated and characterized by NMR and MS spectral analyses.
      Formation of benzoxazinone (11) requires the 4-phenolic functional group and the
      conjugated propenoic acid side chain of p-coumaric acid. The mechanism for
      nitrosation at pH 2 was examined by reacting 1 in H(2)(18)O/NaNO(2).

PMID- 11312885
TI  - Isolation and characterization of glyoxal-arginine modifications.
AB  - 5-(4,5-Dihydroxy-2-imino-1-imidazolidinyl)norvaline (1) was identified as the
      only product of the early reaction of arginine with glyoxal, which was slowly
      degraded to N(5)-[[(carboxymethyl)amino](imino)methyl]ornithine (3, N(7)
      carboxymethylarginine). No other structures could be detected within a range of
      pH 4-8 and 20-50 degrees C in reaction conditions. The rates of formation for
      both products increased with pH and temperature. In equilibrium, the vincinal
      diol groups of 1 were 86% trans configured. The formation of 1 was reversible, as
      could be shown by cis-trans isomerization of the separated isomers and by
      regeneration of arginine in the presence of the alpha-dicarbonyl trapping
      reagents, o-phenylenediamine and aminoguanidine. Both 1 and 3 were converted to 5
      (2-imino-5-oxo-1-imidazolidinyl)norvaline (2) only under strong acidic
      conditions.

PMID- 11312886
TI  - 1,4-Dimethoxyglucobrassicin in Barbarea and 4-hydroxyglucobrassicin in
      Arabidopsis and Brassica.
AB  - A novel indole glucosinolate, 1,4-dimethoxyglucobrassicin (1,4-dimethoxyindol-3
      ylmethylglucosinolate), was isolated as the desulfo derivative from roots of the
      P-type of Barbarea vulgaris ssp. arcuata, and its structure was determined by
      spectroscopy including 2D NMR spectroscopy. 4-Hydroxyglucobrassicin (4
      hydroxyindol-3-ylmethylglucosinolate) was isolated as the desulfo derivative from
      green siliques (fruits) of Arabidopsis thaliana and identified by comparison of
      its (1)H NMR spectrum with the spectrum of the known desulfoglucosinolate from
      Brassica napus. The delayed elution of desulfo indole glucosinolates from the
      DEAE Sephadex column used in sample preparation was examined, and the diode-array
      UV spectra of desulfo indole glucosinolates were measured, to ensure a reliable
      determination of 1,4-dimethoxyglucobrassicin and 4-hydroxyglucobrassicin with the
      existing analysis method based on the HPLC of desulfoglucosinolates. 1,4
      Dimethoxyglucobrassicin was not detected in 10 other Arabidopsis, Brassica, and
      Barbarea species, indicating an evolutionarily recent mutation in the indole
      glucosinolate biosynthesis in B. vulgaris ssp. arcuata type P.

PMID- 11312887
TI  - Identification of alpha-tocopherol oxidation products in triolein at elevated
      temperatures.
AB  - The effect of high-temperature treatment on the stability of alpha-tocopherol (1)
      in triolein was assessed under a reduced-pressure atmosphere (4-40 mbar)
      simulating the deodorization step of the refining of vegetable oils. A marked
      degradation of 1 was observed, which increased with increasing temperature (180
      260 degrees C) and heating time (20-80 min). The degradation of 1 in triolein at
      240 degrees C was inhibited by the addition of the synthetic antioxidant TBHQ or
      when heating was performed under nitrogen atmosphere, indicating oxidative
      degradation. The oxidation products were isolated and identified as alpha
      tocopherolquinone (2), 4a,5-epoxy-alpha-tocopherolquinone (3), and 7,8-epoxy
      alpha-tocopherolquinone (4).

PMID- 11312888
TI  - Characterization of yam bean (Pachyrhizus erosus) proteins.
AB  - Seed proteins from Mexican yam bean seeds (Pachyrhizus erosus L.) were
      sequentially extracted according to the Osborne classification. Albumins were the
      major fraction (52.1-31.0%), followed by globulins (30.7-27.5%). The minor
      protein fraction was prolamins (0.8%). Defatting with chloroform/methanol
      remarkably affected the distribution of protein solubility classes; albumins were
      the most affected fraction (4.3-17.5%). Electrophoretic patterns of albumins
      showed bands at 55, 40, 35, and 31 kDa. After reduction of the globulin fraction
      exhibited two triplets, one from 35 to 31 kDa and the second from 19 to 21 kDa,
      these could be compared to the acid and basic polypeptides of 11S-like proteins.
      Prolamins showed one band at 31 kDa, and glutelins after reduction showed three
      main bands at 52, 27, and 14 kDa. Trypsin inhibitors were assayed in saline
      extracts; the values found (1232-2608 IU/g of meal) were lower than those of
      other legumes. In general, yam bean seed proteins showed an excellent balance of
      all essential amino acids; albumins contain the highest amount of essential amino
      acids.

PMID- 11312889
TI  - Carotenoid composition in the fruits of red paprika (Capsicum annuum var.
      lycopersiciforme rubrum) during ripening; biosynthesis of carotenoids in red
      paprika.
AB  - The changes in the carotenoid pigments of the Capsicum annuum var.
      lycopersiciforme rubrum during maturation have been investigated quantitatively
      by means of a HPLC technique. In all of the chromatograms, 40 peaks were
      detected; 34 carotenoids were identified. The total carotenoid content of the
      ripe fruits was about 1.3 g/100 g of dry weight, of which capsanthin constituted
      37%, zeaxanthin was 8%, cucurbitaxanthin A was 7%, capsorubin constituted 3.2%,
      and beta-carotene accounted for 9%. The remainder was composed of capsanthin 5,6
      epoxide, capsanthin 3,6-epoxide, 5,6-diepikarpoxanthin, violaxanthin,
      antheraxanthin, beta-cryptoxanthin, and several cis isomers and furanoid oxides.
      The possible biosynthetic routes for the formation of minor carotenoids
      containing 3,5,6-trihydroxy-beta-, 3,6-epoxy-beta-, and 6-hydroxy-gamma-end
      groups are described.

PMID- 11312890
TI  - Influence of glyphosate on amino acid composition of Egyptian broomrape.
AB  - The parasitic plant broomrape is entirely dependent on its host for reduced
      carbon and nitrogen and is also susceptible to inhibition by glyphosate that is
      translocated to the parasite through a host. Studies were conducted to examine
      the effect of broomrape parasitism on amino acid concentrations of two hosts:
      common vetch that is tolerant of low levels of glyphosate and oilseed rape that
      has been genetically engineered for glyphosate resistance. The influence of
      glyphosate on the amino acid content of broomrape and the two hosts was also
      examined. Amino acid concentrations in leaves and roots of parasitized common
      vetch plants were generally similar to those of the corresponding tissues of
      nonparasitized plants. Amino acid concentrations in broomrape were lower than
      those of the parasitized common vetch root. For common vetch, glyphosate applied
      at rates that selectively inhibited broomrape growth did not alter individual
      amino acid concentrations in the leaves, but generally increased amino acid
      levels at 0.18 kg ha-1. Glyphosate application also increased the amino acid
      concentrations, with the exception of arginine, of broomrape growing on common
      vetch and did not generally influence concentrations in leaves or roots of common
      vetch. In oilseed rape, parasitization by broomrape generally led to higher amino
      acid concentrations in leaves but lower concentrations in roots of parasitized
      plants. Broomrape had higher amino acid concentrations than roots of the
      parasitized oilseed rape. Glyphosate applied at 0.25 and 0.5 kg ha-1 generally
      increased the amino acid concentrations in oilseed rape leaves, but the 0.75 kg
      ha-1 application caused the amino acid concentrations to decrease compared to
      those of untreated plants. In oilseed rape root the general trend was an increase
      in the concentration of amino acids at the two highest rates of glyphosate.
      Individual amino acid concentrations in broomrape attachments growing on oilseed
      rape were generally increased following glyphosate application of 0.25 kg ha-1.
      These results indicate that low rates of glyphosate alter amino acid profiles in
      both host and broomrape and raise questions about the regulation of amino acid
      metabolism in the parasite.

PMID- 11312891
TI  - Elucidation of protein-lipid interactions in a lysozyme-corn oil system by
      Fourier transform Raman spectroscopy.
AB  - Lysozyme (25% in D2O, corn oil, and their emulsions (10% w/w oil/D2O solution)
      were examined by Fourier transform Raman spectroscopy. Emulsions showed three
      layers, namely, top oil, middle cream, and bottom aqueous layers. Raman spectral
      analysis revealed hydrophobic interactions involving both protein and lipid
      components. Compared to lysozyme in D2O, the difference spectrum obtained after
      subtraction of oil from the cream layer spectrum showed reduced intensity of
      tryptophan bands at 760, 1013, 1340, and 1360 cm(-)(1), reduced intensity ratio
      of the tyrosine doublet at 850 and 830 cm(-)(1), and increased intensity of the C
      H bending band at 1455 cm(-)(1). Compared to corn oil, the difference spectrum
      after subtraction of lysozyme from the cream layer spectrum indicated decreased
      intensity at 2855 cm(-)(1) (lipid CH(2) symmetric stretch) and 3011 cm(-)(1)
      (unsaturated fatty acid hydrocarbon chain =C-H stretch) and a higher intensity
      ratio of the C-H stretching band at 2900 cm(-)(1) to bands at 2885 and 2933 cm(
      )(1). Spectra of the top and bottom layers resembled corn oil and lysozyme,
      respectively, except for changes in the D2O band. Raman spectroscopy can be used
      to detect structural changes in proteins, lipids, and D2O due to protein-lipid
      interactions.

PMID- 11312892
TI  - Authentication of vegetable oils by bulk and molecular carbon isotope analyses
      with emphasis on olive oil and pumpkin seed oil.
AB  - The authenticity of vegetable oils consumed in Slovenia and Croatia was
      investigated by carbon isotope analysis of the individual fatty acids by the use
      of gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS), and
      through carbon isotope analysis of the bulk oil. The fatty acids from samples of
      olive, pumpkin, sunflower, maize, rape, soybean, and sesame oils were separated
      by alkaline hydrolysis and derivatized to methyl esters for chemical
      characterization by capillary gas chromatography/mass spectrometry (GC/MS) prior
      to isotopic analysis. Enrichment in heavy carbon isotope ((13)C) of the bulk oil
      and of the individual fatty acids are related to (1) a thermally induced
      degradation during processing (deodorization, steam washing, or bleaching), (2)
      hydrolytic rancidity (lipolysis) and oxidative rancidity of the vegetable oils
      during storage, and (3) the potential blend with refined oil or other vegetable
      oils. The impurity or admixture of different oils may be assessed from the
      delta(13)C(16:0) vs. delta(13)C(18:1) covariations. The fatty acid compositions
      of Slovenian and Croatian olive oils are compared with those from the most
      important Mediterranean producer countries (Spain, Italy, Greece, and France).

PMID- 11312893
TI  - Preparative-scale isolation of four anthocyanin components of black currant
      (Ribes nigrum L.) fruits.
AB  - Four anthocyanin components of black currant, delphinidin 3-O-beta-rutinoside
      (D3R), cyanidin 3-O-beta-rutinoside (C3R), delphinidin 3-O-beta-glucoside (D3G),
      and cyanidin 3-O-beta-glucoside (C3G), were successfully isolated as crystalline
      forms on a preparative scale. In this process, selective hydrolysis of the
      glucosides (D3G and C3G) and rhamnosides (D3R and C3R) was achieved by treatment
      with beta-glucosidase and hesperidinase (alpha-rhamnosidase), respectively, to
      improve resolution of anthocyanin components. Especially, selective conversion of
      the rutinosides into glucosides made the amounts of D3G and C3G increase about 4-
      and 7-fold, respectively. D3R, C3R, D3G, and C3G were isolated from enzymatic
      hydrolysates of black currant anthocyanins through Amberlite XAD-7HP absorption
      followed by preparative HPLC separation, and their crystals were obtained as the
      flavylium chloride.

PMID- 11312894
TI  - Orally administered delphinidin 3-rutinoside and cyanidin 3-rutinoside are
      directly absorbed in rats and humans and appear in the blood as the intact forms.
AB  - Four components of black currant anthocyanins (BCA), delphinidin 3-O-beta
      rutinoside (D3R), cyanidin 3-O-beta-rutinoside (C3R), delphinidin 3-O-beta
      glucoside (D3G), and cyanidin 3-O-beta-glucoside (C3G), were found to be directly
      absorbed and distributed to the blood and excreted into urine as the glycosylated
      forms. In a rat study, following oral administration of purified D3R, C3R, and
      C3G (800 micromol/kg of body weight), the anthocyanins were detected in the
      plasma and the C(max) values were 580 +/- 410, 850 +/- 120, and 840 +/- 190
      nmol/L, respectively, 0.5-2.0 h after administration. In a human study, when a
      mixture of BCA [6.24 micromol (3.58 mg) consisting of 2.75 micromol (1.68 mg) of
      D3R, 2.08 micromol (1.24 mg) of C3R, 1.04 micromol (0.488 mg) of D3G, and 0.37
      micromol (0.165 mg) of C3G/kg of body weight)] was orally ingested by eight
      volunteers, D3R, C3R, D3G, and C3G were detected in the plasma and urine. The
      plasma C(max) values were 73.4 +/- 35.0, 46.3 +/- 22.5, 22.7 +/- 12.4, and 5.0 +/
      3.7 nmol/L, respectively, 1.25-1.75 h after intake, and the cumulative excretion
      of the four compounds in urine in the period 0-8 h after intake was 0.11 +/-
      0.05% of the dose ingested. These results indicate that 3-O-beta-rutinosyl
      anthocyanins were directly absorbed and distributed to the blood.

PMID- 11312895
TI  - Mungbean [Vigna radiata (L.) Wilczek] globulins: purification and
      characterization.
AB  - Vicilin type (8S) and basic 7S globulins and legumin type (11S) globulins were
      isolated from mungbean [Vigna radiata (L.) Wilczek]. The native molecular weights
      of the different globulin types were 360000 for legumin, 200000 for vicilin, and
      135000 for basic 7S. Some of the 8S globulin apparently complexed and coeluted
      with the 11S on gel filtration. On SDS-PAGE, 11S was composed of two bands of
      40000 and 24000, 8S was composed of 60000, 48000, 32000, and 26000 bands, and
      basic 7S was composed of 28000 and 16000 bands. The percent composition of total
      globulins was estimated to be as follow: 8S, 89%; basic 7S, 3.4%; and 11S, 7.6%.
      The basic 7S and 11S but not the 8S globulins were found to have disulfide bonds.
      The presence of carbohydrates by conjugated peroxidase reaction was observed in
      all bands of 8S, the acidic polypeptide of basic 7S, and its complex but not in
      11S. The 28000 basic 7S band and its 42000 complex and the first three major
      bands of 8S cross-reacted with antibodies to all types of soybean conglycinin
      subunits (alpha, alpha', and beta), whereas the fourth band cross-reacted only
      with the anti-beta subunit. None of the mungbean globulins cross-reacted with
      anti-soybean glycinin. Basic 7S was found to be easily extracted with 0.15 M
      NaCl, 11S was extracted with 0.35 M NaCl,and 8S was extracted over a wide range
      of NaCl concentrations. The N-terminal sequences of the different
      subunits/fragments of the globulins were determined and found to have strong
      homology with storage proteins of other legumes and crops.

PMID- 11312896
TI  - Effect of phosphate on stability of pyridoxal in the presence of lysine.
AB  - The stability of the biologically active compound vitamin B(6) in aqueous
      solution was investigated. Schiff base formation is the major reaction between
      the epsilon-amino group of lysine and the aldehyde group of both pyridoxal and
      pyridoxal phosphate. Model systems composed of equal molar concentrations of
      lysine with either pyridoxal or pyridoxal phosphate were used to study the effect
      of proton transfer on Schiff base formation. Pyridoxylidenelysine was found to be
      the major product in both lysine/pyridoxal and lysine/pyridoxal phosphate
      systems. Quantitation of residual pyridoxal and pyridoxal phosphate was conducted
      using an HPLC to evaluate the degradation of pyridoxal and pyridoxal phosphate.
      The results indicate both the free phosphate ion in the buffer system and the
      bound phosphate on pyridoxal phosphate can enhance the formation of the Schiff
      base. The phosphate group serves as both proton donor and acceptor, which
      catalyzes the Schiff base formation. The aldehyde group on pyridoxal phosphate
      was found to be much more reactive than that on pyridoxal. The bound phosphate
      group on pyridoxal phosphate, with proton donating and accepting groups in close
      proximity, can simultaneously donate and accept protons, thus enhancing Schiff
      base formation between the aldehyde group and the epsilon-amino group. The
      deterioration rate of pyridoxal phosphate was faster than that of pyridoxal in an
      aqueous system.

PMID- 11312897
TI  - Antagonism of free-radical-induced damage of adlay seed and its antiproliferative
      effect in human histolytic lymphoma U937 monocytic cells.
AB  - The goal of our current research was to investigate the antioxidative effects of
      methanolic extracts from different parts of adlay seed and their
      antiproliferative activity in malignant human cells. The methanolic extracts from
      different parts of adlay seeds were from the hull (AHM), testa (ATM), bran (ABM),
      and polished adlay (PAM). AHM exhibited greater capacity to scavenge superoxide
      anion radicals in the PMS-NADH system than ATM, ABM, or PAM. The scavenging
      capacities of AHM and ATM on hydrogen peroxides were about 20% at a dose of 250
      microg/mL. Using the method of deoxyribose degradation to assess damage caused by
      hydroxyl radicals, AHM was found to inhibit damage in deoxyribose at a higher
      concentration. However, ATM, ABM, and PAM exhibited prooxidative activity at the
      same concentration. The inhibitory effect on enzymatic oxidation of xanthine to
      uric acid was found to follow the order AHM > ATM =. ABM. However, PAM was
      inactive. All test samples were positive for inhibition of TPA-induced free
      radical formation on neutrophil-like leukocytes and were found to follow the
      order AHM > ATM > ABM > PAM. When human histolytic lymphoma U937 monocytic cells
      were exposed to tert-butyl hydroperoxide, AHM protected the cells against the
      cytotoxicity caused by tert-butyl hydroperoxide. In addition, AHM exhibited
      antiproliferative activity against human histolytic lymphoma U937 monocytic cells
      in a dose-dependent manner. The antiproliferative properties of AHM appear to be
      attributable to its induction of apoptotic cell death as determined by flow
      cytometry. These results show that AHM displays multiple antioxidant effects and
      induces apoptosis of malignant human cells.

PMID- 11312898
TI  - Antipeptide antibodies recognizing plasmin sensitive sites in bovine beta-casein
      sequence.
AB  - To investigate plasmin activity in cheese, we produced antibodies to bovine beta
      casein with controlled specificity, suitable as markers of the integrity of the
      major bonds involved in its initial breakdown. Sixteen rabbits were immunized
      with synthetic substitutes for six plasmin-sensitive peptides. Antisera raised to
      the peptides (f20-39), (f40-56), (f94-113), (f184-202), and (f193-209) recognized
      beta-casein in ACP-ELISA, Western-blot, and biosensor assays. Casein in vitro
      hydrolysis by plasmin or chymosin reduced the detection of these determinants in
      ACP-ELISA, in agreement with the enzymatic sensitivity of bonds included within
      the binding sites, or in their neighborhood. Antiserum to (f20-39) in particular
      allowed the specific detection of plasmin cleavage at the bond generating gamma1
      CN. Antisera to C-terminus preferentially detected the cleavage by chymosin.
      Immunoassays using these antibodies would allow in situ monitoring of significant
      proteolysis events without bias originated in the secondary degradation of the
      released peptides.

PMID- 11312899
TI  - Effect of galactomannans on the thermal and rheological properties of sago
      starch.
AB  - The thermal and rheological properties of sago starch have been studied in the
      presence of various concentrations of locust bean gum and guar gum of various
      molecular masses. At the concentrations studied (<1%) the galactomannans gave
      rise to only a very slight increase in the gelatinization temperature (up to 0.6
      degrees C), and the gelatinization enthalpy remained constant within experimental
      error. For the low molecular mass galactomannans, depending on the concentration,
      the storage modulus, G', of the mixtures remained constant or actually decreased,
      and tan delta remained very low (0.01-0.03 at 0.1 Hz), indicating strong elastic
      gels. For the higher molecular mass samples G' increased significantly; however,
      the loss modulus, G' ', increased proportionally to a greater extent, and at 1%
      galactomannan tan delta was approximately 0.20 at 0.1 Hz, indicating a reduction
      in elastic character. The systems were shown to undergo phase separation, and the
      variations in rheological properties have been discussed in the context of their
      phase behavior and the relative rates of the phase separation and gelation
      processes. The presence of galactomannans significantly improved the freeze-thaw
      stability.

PMID- 11312900
TI  - Heat-induced gelation of chicken Pectoralis major myosin and beta-lactoglobulin.
AB  - The denaturation, aggregation, and rheological properties of chicken breast
      muscle myosin, beta-lactoglobulin (beta-LG), and mixed myosin/beta-LG solutions
      were studied in 0.6 M NaCl, 0.05 mM sodium phosphate buffer, pH 7.0, during
      heating. The endotherm of a mixture of myosin and beta-LG was identical to that
      expected if the endotherm of each protein was overlaid on the same axis. The
      maximum aggregation rate (AR(max)) increased, and the temperature at the AR(max)
      (T(max)) and initial aggregation temperature (T(o)) decreased as the
      concentration of both proteins was increased. The aggregation profile of <0.5%
      myosin was altered by the presence of 0.25% beta-LG. Addition of 0.5-3.0% beta-LG
      decreased storage moduli of 1% myosin between 55 and 75 degrees C, but increased
      storage moduli (G') when heated to 90 degrees C and after cooling. beta-LG had no
      effect on the gel point of > or =1.0% myosin, but enhanced gel strength when
      heated to 90 degrees C and after cooling. After cooling, the G' of 1%
      myosin/2%beta-LG gels was about 1.7 times greater than that of gels prepared from
      2% myosin/1% beta-LG.

PMID- 11312901
TI  - Structure determination of a novel 3(6H)-pyranone chromophore and clarification
      of its formation from carbohydrates and primary amino acids.
AB  - An intensely orange compound, which has recently been evaluated as one of the
      main colored compounds formed in Maillard reactions of hexoses, could be
      unequivocally identified as (Z)-2-[(2-furyl)methylidene]-5,6-di(2-furyl)-6H-pyran
      3-one (1) by application of several NMR and LC-MS experiments. To clarify its
      formation, the effectiveness of certain carbohydrate degradation products as
      precursors of 1 was studied in a quantitative experiment demonstrating hydroxy-2
      propanone, furan-2-aldehyde, and 3-deoxy-2-hexosulose as precursors of the
      colorant. Site-specific labeling experiments with D-1-[(13)C]glucose and D-6
      [(13)C]glucose, respectively, were performed to elucidate the formation pathway
      of 1 involving a cleavage of the hexose skeleton between carbon atoms C(5) and
      C(6). In addition, pentoses could be shown to generate 1 via a similar formation
      pathway involving the 3-deoxy-2-pentosulose.

PMID- 11312902
TI  - Isolation of a series of apocarotenoids from the fruits of the red paprika
      Capsicum annuum L.
AB  - Eleven apocarotenoids (1-11) including five new compounds, 4, 6, 9, 10 and 11,
      were isolated from the fruits of the red paprika Capsicum annuum L. The
      structures of new apocarotenoids were determined to be apo-14'-zeaxanthinal (4),
      apo-13-zeaxanthinone (6), apo-12'-capsorubinal (9), apo-8'-capsorubinal (10), and
      9,9'-diapo-10,9'-retro-carotene-9,9'-dione (11) by spectroscopic analysis. The
      other six known apocarotenoids were identified to be apo-8'-zeaxanthinal (1), apo
      10'-zeaxanthinal (2), apo-12'-zeaxanthinal (3), apo-15-zeaxanthinal (5), apo-11
      zeaxanthinal (7), and apo-9-zeaxanthinone (8) which have not been previously
      found in paprika. These apocarotenoids were assumed to be oxidative cleavage
      products of C(40) carotenoid such as capsanthin in paprika.

PMID- 11312903
TI  - Antifungal mechanism of polygodial.
AB  - The primary antifungal action of polygodial comes in part from its ability to
      function as a nonionic surfactant, disrupting the lipid-protein interface of
      integral proteins and denaturing their conformation. As a result, the antifungal
      mechanism of this sesquiterpene dialdehyde is associated with the membrane
      functions or derangement of the membrane. For example, the glucose-induced medium
      acidification process of Saccharomyces cerevisiae was inhibited by polygodial,
      presumably caused by inhibition of the plasma membrane H(+)-ATPase. However, the
      potent antifungal activity of polygodial results from its multiple functions.

PMID- 11312904
TI  - Changes in oxygen-scavenging systems and membrane lipid peroxidation during
      maturation and ripening in blackberry.
AB  - Maturation and ripening of blackberry (Rubus sp.) fruit was accompanied by
      decreased activities of oxygen-scavenging enzymes [superoxide dismutase (EC
      1.15.1.1), glutathione-peroxidase (EC 1.11.1.9), catalase (EC 1.11.1.6)] and
      enzymes in the ascorbate-glutathione cycle [ascorbate peroxidase (EC 1.11.1.11),
      monodehydroascorbate reductase (EC 1.6.5.4), dehydroascorbate reductase (EC
      1.8.5.1), and glutathione reductase (EC 1.6.4.2)]. Nonenzyme components in the
      ascorbate-glutathione cycle such as ascorbate (AsA), dehydroascorbate (DHAsA),
      glutathione (GSH), and oxidized glutathione (GSSG) and the ratios of AsA/DHAsA,
      GSH/GSSG were also decreased. These decreases in antioxidant capacity were
      correlated with increases in the ratios of saturated to unsaturated fatty acid of
      polar lipids and free sterols to phospholipids, thus contributing to decreased
      fluidity, enhanced lipid peroxidation, and membrane deterioration, which may be
      associated with ripening and senescence in blackberry fruit.

PMID- 11312905
TI  - Effects of wine phenolics and sorghum tannins on tyrosinase activity and growth
      of melanoma cells.
AB  - In this study, three different phenolic (anthocyanin, other flavonoid, and
      phenolic acid) fractions from wine and a condensed tannin preparation from
      sorghum were tested for their effects on melanogenesis of normal cells and growth
      of human melanoma cells. The wine phenolic fractions decreased melanogenic
      activity (tyrosinase activity) at concentrations that resulted in a slight
      variation in melanocyte viability. Sorghum tannins, however, increased
      melanogenic activity, although no increase was found in total melanin at the
      concentrations that least affect melanocyte viability. Incubation of human
      melanoma cells with the wine fractions and sorghum tannins resulted in a decrease
      in colony formation, although the effect was not dose dependent in all cases.
      These results suggest that all of these phenolic fractions have potential as
      therapeutic agents in the treatments of human melanoma, although the mechanisms
      by which cellular toxicity is effected seem to be different among the fractions.

PMID- 11312906
TI  - Iron availability from iron-fortified spirulina by an in vitro digestion/Caco-2
      cell culture model.
AB  - Iron deficiency, one of the most important nutritional problems in the world, can
      be caused not only by foods deficient in iron but also by poor availability of
      dietary iron. Iron food fortification in combination with highly available iron
      from supplements could effectively reduce this deficiency. The aim of this study
      was to examine the iron availability from iron-fortified spirulina. We have used
      an in vitro digestion/Caco-2 cell culture system to measure iron spirulina
      availability and made a comparison with those of beef, yeast, wheat floor, and
      iron sulfate plus ascorbic acid as a reference. Iron availability was assessed by
      ferritin formation in Caco-2 cells exposed to digests containing the same amount
      of iron. Our results demonstrate a 27% higher ferritin formation from beef and
      spirulina digests than from digests of yeast and wheat flour. When iron
      availability was expressed per microgram of iron used in each digest, a 6.5-fold
      increase appeared using spirulina digest in comparison with meat. In view of this
      observed high iron availability from spirulina, we conclude that spirulina could
      represent an adequate source of iron.

PMID- 11312907
TI  - Metabolism and distribution of [2,3-(14)C]acrolein in lactating goats.
AB  - The metabolism and distribution of [2,3-(14)C]acrolein were studied in a
      lactating goat orally administered 0.82 mg/kg of body weight/day for 5 days.
      Milk, urine, feces, and expired air were collected. The goat was killed 12 h
      after the last dose, and edible tissues were collected. The nature of the
      radioactive residues was determined in milk and tissues. All of the identified
      metabolites were the result of the incorporation of acrolein into the normal,
      natural products of intermediary metabolism. There was evidence that the three
      carbon unit of acrolein was incorporated intact into glucose, and subsequently
      lactose, and into glycerol. In the case of other natural products, the
      incorporation of radioactivity appeared to result from the metabolism of acrolein
      to smaller molecules followed by incorporation of these metabolites into the
      normal biosynthetic pathways.

PMID- 11312908
TI  - Metabolism and distribution of [2,3-(14)C]acrolein in laying hens.
AB  - The metabolism and distribution of [2,3-(14)C]-acrolein were studied in 10 laying
      hens orally administered 1.09 mg/kg of body weight/day for 5 days. Eggs, excreta,
      and expired air were collected. The hens were killed 12-14 h after the last dose
      and edible tissues collected. The nature of radioactive residues was determined
      in tissues and eggs. All of the identified metabolites were the result of the
      incorporation of acrolein-derived radioactivity into normal natural products of
      intermediary metabolism in the hen except for 1,3-propanediol, which is a known
      degradation product of glycerol in bacteria.

PMID- 11312909
TI  - Determination of grayanotoxins in biological samples by LC-MS/MS.
AB  - A rapid LC-MS/MS method was developed for the quantitative determination of
      grayanotoxins I, II, and III in rumen contents, feces, and urine. The
      grayanotoxins were extracted from solid samples with methanol. The methanol
      extract was diluted with water and cleaned up using a reversed phase solid phase
      extraction column. HPLC separation was performed by reversed phase HPLC using a
      gradient of water and methanol containing 1% acetic acid. Determination was by
      positive ion electrospray ionization and ion trap tandem mass spectrometry.
      Grayanotoxin I quantitation was based on fragmentation of the sodium adduct ion
      at m/z 435 to a product ion at m/z 375. Grayanotoxins II and III were quantitated
      on the basis of fragmentation of the ion at m/z 335 to the product ion at m/z
      299. The method detection limits were 0.2 microg/g in rumen contents and feces
      and 0.05 microg/g in urine. Fortifications at the detection limits and 10 times
      the detection limits of bovine rumen contents, caprine feces, and ovine urine
      were recovered in the range 80-114%. The diagnostic utility of the method was
      tested by analyzing samples submitted to the veterinary toxicology laboratory.

PMID- 11312910
TI  - Aquatic humic substances inhibit clastogenic events in germinating seeds of
      herbaceous plants.
AB  - One humic acid (HA) and two fulvic acids (FAs) of aquatic origin have been tested
      for their capacity to inhibit clastogenic events caused by maleic hydrazide (MH)
      in germinating seeds of the herbaceous plant species Allium cepa and Vicia faba.
      Either HA or FA at concentrations of 50 and 500 mg L(-)(1) was interacted with 10
      mg L(-)(1) MH for 24 h before addition to the seeds. The evaluation of genotoxic
      activity was made by counting micronuclei (MN) and aberrant anatelophases (AT) in
      root tip cells after treatment with HA or FA alone, MH alone, and interacted HA +
      MH and FA + MH. Regular AT were also counted as an index of mitotic activity. In
      all cases HA and FA interacted with MH showed an evident anticlastogenic action
      indicated by the marked reduction of genetic anomalies. In A. cepa, the
      anticlastogenic effect of HA and FA was more significant for aberrant AT than for
      MN, whereas the opposite was true in the case of V. faba. The protective effect
      exhibited for both anomalies by HA was slightly higher than that of the
      corresponding FA in A. cepa, whereas no significant differences between these HA
      and FA treatments were observed in the case of V. faba. The two FAs generally
      showed similar anticlastogenic behaviors with slight quantitative differences
      observed as a function of the type of anomaly and the plant species. The effects
      of HA and FA concentration differed depending on the type of anomaly observed,
      the plant species, and FA origin. In V. faba, cell division, that is, the number
      of regular AT, was generally depressed by HA and FA at either concentration with
      respect to the control. In A. cepa, HA and FA produced either stimulating or
      inhibiting effects on regular AT depending on their nature, origin, and
      concentration.

PMID- 11312911
TI  - Behavioral responses of rats exposed to long-term dietary vinclozolin.
AB  - Vinclozolin is a fungicide used on food crops with human exposure estimated at
      approximately 2 microg/kg/day from ingestion; occupational exposure, however, may
      be greater. The metabolites of vinclozolin have been reported to act as
      antiandrogens and have adverse effects on reproductive physiology and behavior in
      animals. Here, pregnant rats were fed soy-free diets containing 0, 10, 150, or
      750 ppm of vinclozolin (approximately 0, 0.8, 12, and 60 mg/kg/day for an adult)
      beginning on gestational day 7, and offspring were continued on these diets
      through sacrifice at postnatal day 77. Male and female offspring were assessed
      for changes in several nonreproductive sexually dimorphic behaviors: open field
      and running wheel locomotor activity, play behavior, and consumption of saccharin
      and sodium chloride-flavored solutions. There was a significant interaction of
      sex with vinclozolin exposure on running wheel activity, which indicated that
      females in the high-dose exposure group were hypoactive compared to same-sex
      controls. There was a significant overall effect of vinclozolin exposure on fluid
      consumption, and high-dose animals showed increased intake of the saccharin
      solution and decreased intake of plain water while saccharin was available.
      Effects were more pronounced in females, which drank 40.8% more saccharin than
      control females, whereas males drank 6.2% more than control males. There were no
      effects of vinclozolin treatment on play behavior or sodium solution intake.
      Gestational duration, total and live pups per litter, litter sex ratios, and
      birth weight were also not significantly affected, nor were body weight and food
      intake for dams and offspring. These results indicate that long-term dietary
      exposure to vinclozolin does not have severe toxicological consequences on the
      nonreproductive behaviors measured here. However, exposure may cause subtle
      alterations in locomotor activity and consumption of saccharin-flavored solution.

PMID- 11312913
TI  - Nonpeptide cholecystokinin-2 receptor agonists.
AB  - In the course of structural explorations around a series of potent CCK2 receptor
      antagonists, it was noted that simple N-methylation of the indolic N-H in the
      parent molecule gave rise to behavior in vivo that was consistent with the
      compound acting as an agonist. Exploration in vitro confirmed this property, and
      it was shown that the agonist action could be blocked by the reference CCK2
      receptor antagonist, L-365,260. Further examples of this type of modification
      were explored, and a common theme with regard to agonist behavior was uncovered.
      Some molecular modeling is also presented in an attempt to throw light on the
      nature of the ligand receptor interactions that may be giving rise to the
      differing properties of these, apparently, structurally similar molecules.

PMID- 11312914
TI  - Mapping and fitting the peripheral benzodiazepine receptor binding site by
      carboxamide derivatives. Comparison of different approaches to quantitative
      ligand-receptor interaction modeling.
AB  - The synthetic-computational approach to the study of the binding site of
      peripheral benzodiazepine receptor (PBR) ligands related to 1-(2-chlorophenyl)-N
      methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195, 1) within their
      receptor (Cappelli et al. J. Med. Chem. 1997, 40, 2910-2921) has been extended. A
      series of carboxamide derivatives endowed with differently substituted planar
      aromatic or heteroaromatic systems was designed with the aim of getting further
      information on the topological requisites of the carbonyl and aromatic moieties
      for interaction with the PBR binding site. The synthesis of most of these
      compounds involves Weinreb amidation of the appropriate lactone as the key step.
      The most potent compound, among the newly synthesized ones, shows a nanomolar PBR
      affinity similar to that shown by 1 and the presence of a basic N-ethyl-N
      benzylaminomethyl group in 3-position of the quinoline nucleus. Thus, it may be
      considered the first example of a new class of water soluble derivatives of 1.
      Several computational methods were used to furnish descriptors of the isolated
      ligands (indirect approaches) able to rationalize the variation in the binding
      affinity of the enlarged series of compounds. Sound QSAR models are obtained by
      size and shape descriptors (volume approach) which codify for the short-range
      contributions to ligand-receptor interactions. Molecular descriptors which
      explicitly account for the electrostatic contribution to the interaction (CoMFA,
      CoMSIA, and surface approaches) perform well, but they do not improve the
      quantitative models. Moreover, useful hints for the identification of the
      antagonist binding site in the three-dimensional modeling of the receptor (direct
      approach) were provided by the receptor hypothesis derived by the pharmacophoric
      approach. The ligand-receptor complexes obtained provided a detailed description
      of the modalities of the interaction and interesting suggestions for further
      experiments.

PMID- 11312915
TI  - Comparative molecular field analysis of dopamine D4 receptor antagonists
      including 3-[4-(4-chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC
      113), 3-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-1H-pyrrolo-[2,3-b]pyridine (L
      745,870), and clozapine.
AB  - A CoMFA study was undertaken to elucidate the correlation of biological activity
      and structural parameters of 25 dopamine D4 antagonists. A special point of
      interest is that we have included the atypical D4 antagonist clozapine as a
      structural template for all other compounds. After comparing potential
      protonation sites at semiempirical (AM1) and ab initio (6-31G(d)) levels of
      theory, possible conformations of the lead compound 3-[4-(4
      chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 113) were
      investigated by systematic semiempirical conformational analysis. The final
      conformation of FAUC 113, which was used as a template for the other compounds in
      the dataset, was chosen by clustering and rigid body alignment of all
      conformations to clozapine. The CoMFA applied on the final alignment resulted in
      a q2cv of 0.739. To elucidate the influence of the absolute orientation of the
      molecules within the grid space, the entire dataset was systematically rotated
      (1296 steps) within the lattice. The Gaussian-shaped distribution of the q2cv
      values spanned the range of 0.699-0.794 and therefore supports the significance
      of the analysis.

PMID- 11312916
TI  - Discovery of an orally active non-peptide fibrinogen receptor antagonist based on
      the hydantoin scaffold.
AB  - Antagonists of the platelet fibrinogen receptor (GP IIb/IIIa receptor) are
      expected to be a promising new class of antithrombotic agents. The binding of
      fibrinogen to the fibrinogen receptor depends on an Arg-Gly-Asp-Ser (RGDS)
      tetrapeptide recognition motif. Structural modifications of the RGDS lead have
      led to the discovery of a non-peptide RGD mimetic GP IIb/IIIa antagonist 44 (S
      1197). Compound 44 inhibited, in a dose dependent and reversible manner, human
      and dog platelet aggregation as well as 125I-fibrinogen binding to ADP-activated
      human gel filtered platelets and isolated GP IIb/IIIa with K(i) values of 9 nM
      and 0.17 nM, respectively. A pharmacophore mapping procedure with QXP and a 3D
      QSAR analysis applying the GRID/GOLPE methodology yielded a stable, rather
      predictive model and revealed structural features which are important for
      binding. Hydrophobic substitutions both at the hydantoin nucleus and at the C
      terminus increase the affinity toward the fibrinogen receptor. The crystalline
      ethyl ester prodrug 48 (HMR 1794) is an orally active antithrombotic agent which
      is a promising drug candidate for the treatment of thrombotic diseases in humans.

PMID- 11312917
TI  - Latent semantic structure indexing (LaSSI) for defining chemical similarity.
AB  - A novel method for computing chemical similarity from chemical substructure
      descriptors is described. This new method, called LaSSI, uses the singular value
      decomposition (SVD) of a chemical descriptor-molecule matrix to create a low
      dimensional representation of the original descriptor space. Ranking molecules by
      similarity to a probe molecule in the reduced-dimensional space has several
      advantages over analogous ranking in the original descriptor space: matching
      latent structures is more robust than matching discrete descriptors, choosing the
      number of singular values provides a rational way to vary the "fuzziness" of the
      search, and the reduction in the dimensionality of the chemical space increases
      searching speed. LaSSI also allows the calculation of the similarity between two
      descriptors and between a descriptor and a molecule.

PMID- 11312918
TI  - Chemical similarity searches using latent semantic structural indexing (LaSSI)
      and comparison to TOPOSIM.
AB  - Similarity searches based on chemical descriptors have proven extremely useful in
      aiding large-scale drug screening. Here we present results of similarity
      searching using Latent Semantic Structure Indexing (LaSSI). LaSSI uses a singular
      value decomposition on chemical descriptors to project molecules into a k
      dimensional descriptor space, where k is the number of retained singular values.
      The effect of the projection is that certain descriptors are emphasized over
      others and some descriptors may count as partially equivalent to others. We
      compare LaSSI searches to searches done with TOPOSIM, our standard in-house
      method, which uses the Dice similarity definition. Standard descriptor-based
      methods such as TOPOSIM count all descriptors equally and treat all descriptors
      as independent. For this work we use atom pairs and topological torsions as
      examples of chemical descriptors. Using objective criteria to determine how
      effective one similarity method is versus another in selecting active compounds
      from a large database, we find for a series of 16 drug-like probes that LaSSI is
      as good as or better than TOPOSIM in selecting active compounds from the MDDR
      database, if the user is allowed to treat k as an adjustable parameter.
      Typically, LaSSI selects very different sets of actives than does TOPOSIM, so it
      can find classes of actives that TOPOSIM would miss.

PMID- 11312919
TI  - Design, synthesis, and structural analysis of influenza neuraminidase inhibitors
      containing pyrrolidine cores.
AB  - The discovery of (+/-)-(2S,3R,4R)-2-(trifluoroacetamido)methyl-3-amino-1-(N'
      ethyl-N'-isopropylcarbamyl)pyrrolidine-4-carboxylic acid (A-192558, 20e) as a
      potent inhibitor of influenza neuraminidase (NA) is described. Efficient
      syntheses of two core structures, cis-3-(allyloxycarbonyl)amino-1-(9'
      fluorenylmethoxycarbonyl)pyrrolidine-4-carboxylic acid (7) and tert-butyl (+/-)
      (2S,3R,4R)-2-aminomethyl-3-bis(tert-butyloxycarbonyl)amino-1-(N'-ethyl-N'
      isopropylcarbamyl)pyrrolidine-4-carboxylate (18b), were developed. Starting with
      these core structures and using available structural information of the NA active
      site as the guide, analogues were synthesized in both the tri- and
      tetrasubstituted pyrrolidine series by means of high-throughput parallel
      synthesis in solid or solution phase for expeditious SAR. These studies
      accelerated the identification of (+/-)-(2S,3R,4R)-2-(trifluoroacetamido)methyl-3
      amino-1-(N-ethyl-N-isopropylcarbamyl)pyrrolidine-4-carboxylate (20e, A-192558) as
      the most potent NA inhibitor in this series (IC50 = 0.2 microM against NA A and 8
      microM against NA B). The X-ray crystallographic structure of A-192558 bound to
      NA revealed the predicted interaction of the carboxylic group with the positively
      charged pocket (Arg118, Arg292, Arg371) and interaction of the trifluoroacetamino
      residue with the hydrophobic pocket (Ile222, Trp178) of the enzyme active site.
      Surprisingly, the ethyl and isopropyl groups of the urea functionality induced a
      conformational change of Glu276, turning the Glu276/Glu277 hydrophilic pocket,
      which normally accommodates the triglycerol side chain of substrate sialic acid,
      into an induced hydrophobic pocket.

PMID- 11312920
TI  - Novel p-arylthio cinnamides as antagonists of leukocyte function-associated
      antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of
      inhibition and structure-based improvement of pharmaceutical properties.
AB  - The interaction between leukocyte function-associated antigen-1 (LFA-1) and
      intracellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory
      and immune diseases. Recently, a novel series of p-arylthio cinnamides has been
      described as potent antagonists of the LFA-1/ICAM-1 interaction. These compounds
      were found to bind to the I domain of LFA-1 using two-dimensional NMR
      spectroscopy of 15N-labeled LFA-1 I domain. On the basis of NOE studies between
      compound 1 and the I domain of LFA-1, a model of the complex was constructed.
      This model revealed that compound 1 does not directly inhibit ICAM-1 binding by
      interacting with the metal ion dependent adhesion site (MIDAS). Instead, it binds
      to the previously proposed I domain allosteric site (IDAS) of LFA-1 and likely
      modulates the activation of LFA-1 through its interaction with this regulatory
      site. A fragment-based NMR screening strategy was applied to identify small, more
      water-soluble ligands that bind to a specific region of the IDAS. When
      incorporated into the parent cinnamide template, the resulting analogues
      exhibited increased aqueous solubility and improved pharmacokinetic profiles in
      rats, demonstrating the power of this NMR-based screening approach for rapidly
      modifying high-affinity ligands.

PMID- 11312921
TI  - Acyl substitution at the ortho position of anilides enhances oral bioavailability
      of thiophene sulfonamides: TBC3214, an ETA selective endothelin antagonist.
AB  - Sitaxsentan (3, TBC11251) (Wu et al. J. Med. Chem. 1997, 40, 1690) is an orally
      active ET(A) selective endothelin antagonist that attenuates pulmonary vascular
      hypertension and cardiac hypertrophy in rats (Tilton et al. Pulm. Pharmacol.
      Ther. 2000, 13, 87). It has demonstrated efficacy in a phase II clinical trial
      for congestive heart failure (Givertz et al. Circulation 2000, 101, 2922). During
      the discovery of 3, we observed several structure-oral bioavailability
      relationships. To investigate whether there is any generality in these trends, we
      synthesized some similar pairs of compounds in the latest series (Wu et al. J.
      Med. Chem. 1999, 42, 4485) and evaluated their oral properties. In both series,
      an acyl group at the 2-position of the anilide of these thiophene sulfonamides
      improved oral bioavailability. As a result of this exercise, TBC3214 (17) was
      identified as a sitaxsentan follow-on candidate. It is very potent (IC(50) for
      ET(A) = 40 pM) and highly selective for ET(A) vs ET(B) receptors (400 000-fold),
      with a half-life of >4 h and oral bioavailability of 25% in rats, 42% in cats,
      and 70% in dogs.

PMID- 11312922
TI  - Synthesis and biological activity of analogues of the antidiabetic/antiobesity
      agent 3-guanidinopropionic acid: discovery of a novel aminoguanidinoacetic acid
      antidiabetic agent.
AB  - 3-Guanidinopropionic acid (1, PNU-10483) has been demonstrated to both improve
      insulin sensitivity and to promote weight loss selectively from adipose tissue in
      animal models of non-insulin-dependent diabetes mellitus (NIDDM). However, 1 has
      also been shown to be a substrate for both the creatine transporter and creatine
      kinase, leading to marked accumulation in muscle tissue as the corresponding N
      phosphate 4. In an effort to identify novel entities that maintain antidiabetic
      potency without susceptibility to creatine-like metabolism, an analogue program
      was undertaken to explore the effects of various structural modifications,
      including homologation, simple substitution, single atom mutations, and
      bioisosteric replacements for the guanidine and carboxylic acid. Overall, the
      scope of activity encompassed by the set of new analogues proved to be
      exceedingly narrow. Notable exceptions demonstrating equivalent or improved
      antidiabetic activity included the alpha-amino derivative 29, aminopyridine 47,
      isothiourea 67, and aminoguanidine 69. On the basis of its superior therapeutic
      ratio, aminoguanidine 69 was selected for preclinical development and became the
      foundation for a second phase of analogue work. Furthermore, in vitro studies
      demonstrated that 69 is markedly less susceptible to phosphorylation by creatine
      kinase than the lead 1, suggesting that it should have less potential for
      accumulation in muscle tissue than 1.

PMID- 11312923
TI  - Synthesis and biological activity of aminoguanidine and diaminoguanidine
      analogues of the antidiabetic/antiobesity agent 3-guanidinopropionic acid.
AB  - 3-Guanidinopropionic acid (1) has been demonstrated both to improve insulin
      sensitivity and to promote weight loss selectively from adipose tissue in animal
      models of non-insulin-dependent diabetes mellitus (NIDDM). However, 1 has also
      been shown to be a substrate for both the creatine transporter and creatine
      kinase, leading to marked accumulation in muscle tissue as the corresponding N
      phosphate. The corresponding aminoguanidine analogue 2 was recently discovered to
      retain the antidiabetic activity of 1 while being markedly less susceptible to
      creatine-like metabolism, suggesting that it should have less potential to
      accumulate in muscle. Further structural modification of 2 was undertaken to
      investigate whether the antidiabetic potency could be augmented while maintaining
      resistance to creatine-like metabolism. Modifications such as alpha-alkylation,
      homologation, and bioisosteric replacement of the aminoguanidine all were
      detrimental to antidiabetic activity. However, the simple regioisomeric
      aminoguanidinoacetic acid 9 and diaminoguanidinoacetic acid analogue 7 were found
      to be equipotent to 2, leading eventually to the discovery of the significantly
      more potent diaminoguanidinoacetic acid regioisomers 52 and 53. Further attempts
      to modify the more active template represented by 52 led only to reductions in
      antidiabetic activity. Each of the new active analogues displayed the same
      resistance to creatine-like metabolism as 2. Further testing of 7, 9, and 53 in
      obese diabetic ob/ob mice confirmed that weight loss is induced selectively from
      adipose tissue, similar to the lead 1. Administration of 53 to insulin-resistant
      rhesus monkeys led to reductions in both fasting and post-prandial plasma glucose
      levels with concomitant reductions in plasma insulin levels, suggesting that the
      compound improved the action of endogenous insulin. Compounds 7 and 53 were
      selected for further preclinical development.

PMID- 11312924
TI  - Angular methoxy-substituted furo- and pyranoquinolinones as blockers of the
      voltage-gated potassium channel Kv1.3.
AB  - The voltage-gated potassium channel Kv1.3 constitutes an attractive target for
      immunosuppression because of its role in T-lymphocyte activation and its
      functionally restricted expression to lymphocytes. Blockade of Kv1.3 channels by
      margatoxin has previously been shown to prevent T-cell activation and attenuate
      immune responses in vivo. In the present study, several furo- and pyranoquinoline
      derivatives were synthesized and screened for their blocking activities of Kv1.3
      channels, stably expressed in mice-fibroblasts L929. In addition the activities
      of the compounds on Kv currents of the neuroblastoma cell line N1E-115 were
      determined. The most potent compounds, the angular furoquinolinone 8-methoxy-2
      (1'-methylethyl)-5-methyl-4,5-dihydrofuro[3,2-c]quinolin-4-one (8c) and the
      angular pyranoquinolinone 9-methoxy-2,2,6-trimethyl-2,6-dihydro-5H-pyrano[3,2
      c]quinolin-5-one (9a), inhibited Kv1.3 channels with half-blocking concentrations
      of 5 and 10 microM, respectively, and displayed 8-fold (8c) and 2-fold (9a)
      selectivity over Kv currents of N1E-115 cells. Thus, compounds 8c and 9a might
      function as a template for the development of novel immunosuppressants.

PMID- 11312925
TI  - New selective cytotoxic diterpenylquinones and diterpenylhydroquinones.
AB  - A new series of diterpenylquinone/hydroquinones has been prepared by Diels-Alder
      cycloaddition between three labdanic diterpenoids (myrceocommunic acid, methyl
      myrceocommunate, and myrceocommunyl acetate) and p-benzoquinone or 1,4
      naphthoquinone. Influences of the quinone/hydroquinone fragment and other
      structural features, such as the different functionalities in the terpenic core,
      are considered in relation to the cytotoxicity toward neoplastic cells and the
      selectivity of these diterpenylnaphthoquinones/hydroquinones and anthraquinones.
      Several compounds showed IC50 values under the micromolar level, and four of
      these derivatives were evaluated at the NCI screening panel. The results showed
      an important selectivity toward renal cancer lines, identifying these compounds
      as a very promising group of antineoplastics.

PMID- 11312926
TI  - Development of orally active nonpeptidic inhibitors of human neutrophil elastase.
AB  - 5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and
      miscellaneous derivatives were synthesized and biologically evaluated on both in
      vitro activity and oral activity in an acute hemorrhagic assay. These compounds
      contained an alpha-keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195
      hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds
      11a-c,e,i-l(F), 11d,e,k(H), 21d,e,k(F), and 21d,e(H) showed a good oral profile.
      RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency,
      duration of action, enzyme selectivity, safety profile, and ease of synthesis.
      Structure-activity relationships (SARs) are discussed.

PMID- 11312927
TI  - Synthesis, structure-activity relationships, and pharmacokinetic profiles of
      nonpeptidic alpha-keto heterocycles as novel inhibitors of human chymase.
AB  - We designed nonpeptidic chymase inhibitors based on the structure of a peptidic
      compound (1) and demonstrated that the combination of a pyrimidinone skeleton as
      a P3-P2 scaffold and heterocycles as P1 carbonyl-activating groups can function
      as a nonpeptidic chymase inhibitor. In particular, introduction of heterobicycles
      such as benzoxazole resulted in more potent chymase-inhibitory activity. Detailed
      structure-activity relationship studies on the benzoxazole moiety and
      substituents at the 2-position of the pyrimidinone ring revealed that 2r (Y
      40079) had the most potent chymase-inhibitory activity (K(i) = 4.85 nM). This
      compound was also effective toward chymases of nonhuman origin and showed good
      selectivity for chymases over other proteases. Pharmacokinetic studies in rats
      indicated that 2r was absorbed slowly after oral administration and showed
      satisfactory bioavailability (BA) (T(max) = 6.0 +/- 2.3 h, BA = 19.3 +/- 6.6%,
      t(1/2) = 35.7 +/- 13.3 h). In conclusion, 2r is a novel, potent, and orally
      active chymase inhibitor which would be a useful tool in elucidating the
      pathophysiological roles of chymase.

PMID- 11312928
TI  - Synthesis, structure-activity relationships, and pharmacokinetic profiles of
      nonpeptidic difluoromethylene ketones as novel inhibitors of human chymase.
AB  - Potent human chymase inhibitors with high enzymatic selectivity and satisfactory
      metabolic stability were obtained by replacing the Val-Pro (P3-P2) dipeptide
      portion of the previously described inhibitor 1 with a nonpeptidic pyrimidinone
      skeleton. The potency of the novel compounds was further enhanced by the
      introduction of carbamoyl-substituted difluoromethylene ketone moieties. The most
      potent chymase inhibitor of the newly created series was 2u (Y-40018), which had
      a K(i) of 2.62 nM. Compound 2u possessed high selectivity for human chymase since
      it lacked significant activity toward other representative human proteolytic
      enzymes. Moreover its strict specificity for human chymase suggested that 2u
      strongly inhibited human and canine chymases but not rat and mouse ones.
      Pharmacokinetic studies in rats and dogs indicated that 2u was absorbed rapidly
      after oral administration and had satisfactory bioavailability in these
      experimental animal species (rat, 17%; dog, 32%). In conclusion, 2u is a novel,
      potent, and orally active chymase inhibitor which would prove very useful in
      revealing the precise roles of the latter in various pathophysiological
      processes.

PMID- 11312929
TI  - Highly potent and subtype selective ligands derived by N-methyl scan of a
      somatostatin antagonist.
AB  - The search for synthetic peptide analogues of somatostatin (SRIF) which exhibit
      selective affinities for the five known receptor subtypes (sst1-5) has generated
      a large number of potent agonists. Some of these agonists display good subtype
      selectivities and affinities for the subtypes 1, 2, 3, and 5, including analogues
      created by N-methyl amino acid substitutions in a standard octapeptide analogue
      format. We have now extended this peptide backbone N-methylation approach to a
      potent somatostatin receptor antagonist series using the antagonist Cpa
      cyclo(DCys-Pal-DTrp-Lys-Thr-Cys)-Nal-NH2 9 reported from this laboratory as the
      lead structure. Synthetic analogues were tested for their ability to inhibit
      somatostatin-stimulated GH release from rat pituitary cells in culture and to
      displace 125I-labeled somatostatin from CHO cells transfected with the five known
      human somatostatin receptors. Several interesting observations resulted from the
      study. N-Methylation at the Lys(9) residue (5) increased the rat GH release
      inhibitory potency nearly 4-fold to 0.73 nM but resulted in little change in the
      binding affinity for human type 2 receptor. This analogue also had a high
      affinity of 5.98 nM for sst5 receptor (compared to 1.4 nM for somatostatin
      itself) and is the first antagonist analogue to be reported with high affinity
      for sst5. It also had high potency on in vitro inhibition of sst5 mediated
      intracellular calcium mobilization. These results were considered surprising,
      since the Lys(9) residue has long been considered to constitute the active center
      of somatostatin, important both for receptor binding and activation, and suggests
      important conformational differences between D-Cys(9) somatostatin antagonists
      and normal agonist structures. More modifications were carried out on this
      analogue with the aim of improving antagonist potency and/or specificity. Tyr(7)
      substitution of 5 resulted in an analogue, which had the highest affinity in the
      series for hsst2 (K(I) 5.51 nM) and an extraordinarily low IC50 of 0.53 nM in the
      rat pituitary cell assay. However, this analogue lost considerable affinity for
      sst5 relative to analogue 5. Analogue 16 with DTrp(12) at C-terminus had the
      highest affinity for hsst2, however, the IC50 in the rat GH release assay was
      only 11.6 nM. Replacement of Lys(9) in 9 with Dab(9) gave 11 which displayed high
      binding affinity for sst3, and it was also quite selective for that receptor.
      Both the sst3 and sst5 antagonists should be of value in assigning the
      physiological roles to type 3 and 5 receptor, respectively.

PMID- 11312930
TI  - General behavior, toxicity, and cytotoxic activity of elenoside, a lignan from
      Justicia hyssopifolia.
AB  - Cytotoxicity, acute toxicity, and general pharmacological effects in mice of an
      arylnaphthalene lignan isolated from Jisticia hyssopifolia were studied.
      Elenoside was cytotoxic to human cancer cell lines in a range of concentrations
      from 10(-5) to 10(-4)M. It has an LD(50), ip in mice, of 305 mg/kg and central
      depressive properties at doses of 25, 50, and 100 mg/kg. Thus, elenoside appears
      to be a sedative with broad spectrum cytotoxicity.

PMID- 11312931
TI  - Intermolecular Michael addition of substituted amines to a sugar-derived
      alpha,beta-unsaturated ester: synthesis of 1-deoxy-D-gluco- and -L-ido
      homonojirimycin, 1-deoxy-castanospermine and 1-deoxy-8a-epi-castanospermine.
AB  - The synthesis of polyhydroxylated piperidine alkaloids, namely, 1-deoxy-D-gluco
      homonojirimycin 3a, 1-deoxy-L-ido-homonojirimycin 3b, and indolizidine alkaloids
      1-deoxy-castanospermine 5a and 1-deoxy-8a-epi-castanospermine 5b, has been
      achieved. The key step involved is the intermolecular Michael addition of
      benzylamine to alpha,beta-unsaturated ester 1, derived from D-glucose, which
      afforded diastereomeric mixture of beta-amino esters 6a and 6b with D-gluco- and
      L-ido- configuration at C5, respectively. Attempts were made to increase and/or
      alter the diastereoselectivity at the newly generated stereocenter. The high
      stereoselectivity, in favor of L-ido-isomer 6b, was achieved under kinetically
      controlled conditions by using lithium N-benzyl amide as a Michael donor. The
      beta-amino esters 6a and 6b represent common intermediates to target molecules.
      Thus, LAH reduction of 6a and 6b, individually, gave beta-amino alcohol 7a and
      7b. Sequential hydrogenolysis, selective protection of the amino group, followed
      by hydrolysis of the 1,2-acetonide functionality, and hydrogenation gave 3a and
      3b, respectively. On the other hand, the beta-amino ester 6a was converted to
      gamma-amino ester 13a by Arndt-Eistert synthesis, which on hydrogenolysis and
      treatment with sodium acetate gave gamma-lactam 14a. The LAH reduction afforded
      pyrrolidene. The N-protection-hydrolysis-hydrogenation cascade successfully
      executed, and 1-deoxy-castanospermine 5a was obtained in good yield. The same
      sequence of reactions was applied to beta-amino ester 6b, which afforded 1-deoxy
      8a-epi-castanospermine 5b.

PMID- 11312932
TI  - Synthesis of unsaturated polyazamacrolides from the ladybird beetle Subcoccinella
      vigintiquatuorpunctata.
AB  - The pupal defensive secretion of the ladybird beetle Subcoccinella
      vigintiquatuorpunctata consists of a mixture of macrocyclic polyamines
      (polyazamacrolides, PAMLs) dominated by three dimeric, 30-membered bislactones
      (1, 2, and 3), which represent the three possible head-to-tail combinations of
      the two building blocks (S)-(Z)-11-(2-hydroxyethylamino)-5-tetradecenoic acid (4)
      and (S)-(5Z,8Z)-11-(2-hydroxyethylamino)-5,8-tetradecadienoic acid (5). We now
      report the synthesis of these three alkaloids via a route involving the
      nucleophilic opening of a chiral aziridine as a common step.

PMID- 11312933
TI  - Synthesis and ring contraction reactions of polyazamacrolides.
AB  - The synthesis of three analogues of the single most abundant component of a
      ladybird beetle (Epilachna borealis) defensive secretion, the trimeric 42
      membered polyazamacrolide PAML 681, is described. Construction of the nonnatural
      macrocyclic trimers began with the preparation of the corresponding monomeric
      segments, followed by their oligomerization and a final macrolactonization step
      of the activated linear trimeric hydroxy acid. The relative rates of the O-to-N
      acyl migrations that are characteristic of PAML 681 itself, as well as of the
      synthetic analogues, were investigated. These studies showed that changes in the
      substitution pattern adjacent to the nucleophilic nitrogen atom, along with
      changes in the size of the oxaazacyclic intermediates, have substantial effects
      on the polyazamacrolide rearrangement rates.

PMID- 11312934
TI  - An examination of the purported reverse anomeric effect beyond acetylated N
      xylosyl- and N-glucosylimidazoles.
AB  - Syntheses of six new N-(pentopyranosyl)imidazoles have been achieved, and their
      conformations were observed with and without protonation. A decisive decrease in
      J(5',4), consistent with stabilization of the 1C4 conformations, was clearly
      observed for three N-(pentopyranosyl)imidazoles. As well, no reverse anomeric
      stabilization was observed for N-(2,3,4-tri-O-acetyl-alpha-D
      lyxopyranosyl)imidazole upon protonation. It is suggested that the previous
      observations of the reverse anomeric effect were due to the slight increase in
      steric bulk of the imidazole aglycone upon protonation, along with favorable
      dipolar interactions between ring substituents, and not by a reverse of the
      anomeric effect.

PMID- 11312935
TI  - Relevance of torsional effects to the conformational equilibria of 1,5-diaza-cis
      decalins: a theoretical and experimental study.
AB  - 1,5-Diaza-cis-decalin populates two conformations in which the nitrogen atoms are
      either gauche (N-in) or anti (N-out) to one another. The equilibrium mixture of
      the two conformers depends on the substituents at the nitrogen atom, as well as
      the reaction conditions. Ab initio (HF/6-31G, B3LYP/6-31+G) and molecular
      mechanics (Amber) calculations have been performed to examine the possible role
      of stereoelectronics and steric effects in controlling the equilibrium of
      substituted 1,5-diaza-cis-decalins. In the present study, N,N'-diethyl- and N,N'
      bistrifluoroethyl-1,5-diaza-cis-decalins have been synthesized, and the
      equilibrium mixtures have been measured using 1H and 13C NMR experiments. Steric
      effects appear to control the equilibria between the two conformational isomers
      of 1,5-diaza-cis-decalin while torsional effects appear to dominate the
      equilibria for the N,N'-dialkyl derivatives.

PMID- 11312936
TI  - Studies of 9-fluorenyl carbocations. intramolecular hydride migration in a
      substituted 9-fluorenyl carbocation.
AB  - The substituted fluorenyl cation, 9-(diphenylmethyl)fluoren-9-yl cation (4), is
      formed under stable ion conditions (low temperature/strong acid) from its
      corresponding alcohol 3. This ion is transformed to a substituted diphenyl methyl
      cation 8 at ambient temperature via an apparent 1,2-hydrogen shift. Irradiation
      of 9-(diphenylmethyl)fluoren-9-ol in methanol gives products derived from the
      corresponding cation along with radical-derived products from C-C and C-O
      homolysis processes. The laser flash photolysis of this alcohol gave a transient
      corresponding to cation 4. All of the photoproducts are derived from cation 4 or
      radical pathways. High level MO calculations point to a high barrier (23.8 kcal x
      mol(-1)) for the 1,2-hydride shift. This barrier is the consequence of the
      minimum energy conformation of this fluorenyl cation which is less than ideal for
      the periplanar geometry necessary for this process.

PMID- 11312937
TI  - Beta-trimethylsilyl cyclopropylcarbenes.
AB  - Thermal decomposition of the in situ generated lithium salt of the tosylhydrazone
      derivative of cyclopropyl trimethylsilylmethyl ketone gave 1-cyclopropyl-1
      trimethylsilylethylene, a product of exclusive silyl migration. Thermal
      decomposition of the sodium salts of tosylhydrazone derivatives of 1
      trimethylsilylcyclopropyl alkyl ketones also gave methylenecyclopropane products
      derived from trimethylsilyl migration. These reactions were interpreted in terms
      of rapid trimethylsilyl migration to carbene-like centers that compete
      effectively with ring expansion processes of cyclopropylcarbenes. Computational
      studies (B3LYP/6-31G) suggest that cyclopropyl stabilization of carbenes is more
      effective than beta-trimethylsilyl stabilization. However, beta-trimethylsilyl
      stabilized conformations are easily attained, and these conformations can lead to
      silyl migrations. There are two minimum energy conformations of methyl-1
      trimethylsilylcyclopropylcarbene, 27, and the rotational barrier to
      interconversion of these conformations (5.4 kcal/mol) is substantially lower than
      in the parent cyclopropylcarbene (15 kcal/mol). The onset of a stabilizing
      interaction in the transition state between the carbene vacant orbital with the
      adjacent Si-C sigma-orbital is proposed. Computational studies also show a very
      small (2.0 kcal/mol) barrier for trimethylsilyl migration in trimethylsilylmethyl
      cyclopropylcarbene, 11.

PMID- 11312938
TI  - Absolute configuration, predominant conformations, and vibrational circular
      dichroism spectra of enantiomers of n-butyl tert-butyl sulfoxide.
AB  - Alkylation of the alpha-carbanion of (R)-(-)-tert-butyl methyl sulfoxide (4) with
      n-propyl bromide afforded (+)-n-butyl tert-butyl sulfoxide (1) to which the
      absolute configuration (R) was ascribed. This assignment was confirmed by X-ray
      analysis of the complex 6 obtained from the enantiomerically pure sulfoxide (-)-1
      and mercury chloride. Vibrational absorption and circular dichroism spectra of
      (+)-1 were measured in CDCl3 solution in the 2000-900 cm(-1) region and compared
      with the ab initio predictions of absorption and VCD spectra obtained with
      density functional theory using the B3LYP/6-31G basis set for different
      conformers of (R)-1. This comparison indicated also that (+)-1 is of the (R)
      configuration.

PMID- 11312939
TI  - A new photochromic 8pi-system based on an azaheptatriene
      tetrahydroazepinoisoquinoline electrocyclization.
AB  - A new photochromic family of tetrahydroazepinoisoquinolines (THAI) 4a-i has been
      prepared. It undergoes light-induced ring opening from spiro compounds 4 to
      betaines 3 that decolorize in a very fast cyclizing reaction. Depending on
      substitution of the precursors 1 and 6, the photochromic
      styryltetrahydroindolizines (THI) 5k-q are formed in a periselective way. The
      conformation and configuration of the new photochromic THAI 4 and THI 5 were
      investigated by NMR and the structure of both compounds was proven by X-ray
      analysis. The photochromic properties were studied by laser flash photolysis,
      which afforded the lifetime of the colored form 3 and 3' in the micro- or
      nanosecond range.

PMID- 11312941
TI  - Factors influencing the C-O bond homolysis of alkoxyamines: effects of H-bonding
      and polar substituents.
AB  - The synthesis of various new trialkylhydroxylamines is described. The rate
      constant of the C-O bond cleavage of these new alkoxyamines has been measured.
      For example, C-O bond homolysis rates in a series of para-substituted TEMPO
      styryl compounds TEMPO-CH(CH3)C6H5X 1a (p-MeO), 1b (p-Me), 1d (p-H), 1e (p-Br),
      and 1f (p-MeO2C) are presented. Furthermore, rate constants for the C-O bond
      cleavage of alpha-heteroaryl-substituted secondary alkoxyamines are discussed. A
      correlation by which the rate constant for the C-O bond cleavage of TEMPO-derived
      alkoxyamines can be predicted from the C-H BDEs of the corresponding alkanes is
      presented. Solvent effects as well as the effect of camphorsulfonic acid on the
      rate of the C-O bond homolysis are discussed. Finally, EPR and kinetic evidence
      show that alkoxyamines derived from nitroxides which are capable of
      intramolecular H-bonding undergo C-O bond cleavage faster than the corresponding
      non-H-bond-forming analogues.

PMID- 11312940
TI  - Ab initio calculation of inner-sphere reorganization energies of arenediazonium
      ion couples.
AB  - The geometries of a series of substituted arenediazonium cations (p-NO2, p-CN, p
      Cl, p-F, p-H, m-CH3, p-CH3, p-OH, p-OCH3, p-NH2) and the corresponding diazenyl
      radicals were optimized at the HF/6-31G, MP2/6-31G, B3LYP/6-31G, B3LYP/TZP,
      B3PW91/TZP, and CASSCF/6-31G levels of theory. Inner-sphere reorganization
      energies for the single electron-transfer reaction between the species were
      computed from the optimized geometries according to the NCG method and compared
      to experimental values determined by Doyle et al. All levels of theory predicted
      a CNN bond angle of 180 degrees in the cation. A bent neutral diazenyl radical
      was predicted at all levels of theory excepting B3LYP/TZP and B3PW91/TZP for the
      p-Cl-substituted compound. Inner-sphere reorganization energies determined at the
      HF, MP2, and CASSCF levels of theory correlated poorly with both experimental
      results and calculated geometries. Density functional methods correlated best
      with the experimental values, with B3LYP/6-31G yielding the most promising
      results, although the ROHF/6-31G survey also showed some promise. B3LYP/6-31G
      calculations correctly predicted the order of the inner-sphere reorganization
      energies for the series, excluding the halogen-substituted compounds, with values
      ranging from 42.8 kcal x mol(-1) for the p-NO2-substituted species to 55.1 kcal x
      mol(-1) for NH2. The magnitudes of these energies were lower than the
      experimental by a factor of 2. For the specific cases examined, the closed-shell
      cation geometries showed the expected geometry about the CNN bond, with
      variations in the CN and NN bond lengths correlating with the electron
      donating/withdrawing capacity of the substituent. As predicted by Doyle et al., a
      large geometry change was observed upon reduction. The neutral diazenyl radicals
      showed a nominal CNN bond angle of 120 degrees and variations in the CN and NN
      bond lengths also correlated with the electron-donating/withdrawing capacity of
      the substituent. Changes in theta(CNN) and r(CN) both correlated well with
      calculated lambda(inner). The key parameters influencing inner-sphere
      reorganization energy were the CN and NN bond lengths and the CNN bond angle.
      This influence is explained qualitatively via resonance models produced from NRT
      analysis and is related to the amount of CN double bond character. Based on these
      observations, B3LYP/6-31G calculations are clearly the most amenable for
      calculating inner-sphere reorganization energies for the single electron-transfer
      reaction between cation/neutral arenediazonium ion couples.

PMID- 11312942
TI  - The influence of substituent groups on the resonance stabilization of benzene. An
      ab initio computational study.
AB  - Accurate G3(MP2) calculations of the enthalpies of formation (Delta(f)H298) of
      organic molecules permit replication and extension of calculations that were
      formerly dependent on experimental thermochemical results. A case in point is
      Kistiakowski's classical calculation of the total stabilization enthalpy of
      benzene relative to that of cyclohexene, called for many years the "resonance
      energy". This paper investigates extension of the classical calculation to
      substituted benzenes. Slight modification of the usual procedure for Delta(f)H298
      determination permits exclusion of all empirical information, leaving a purely ab
      initio result. Stabilization enthalpies relative to the corresponding 4
      substituted cyclohexenes are presented for benzene, toluene, aniline, phenol,
      phenylacetylene, styrene, ethylbenzene, and phenylhydrazine. In the process of
      calculating these stabilization enthalpies, we have also obtained 42 values of
      Delta(f)H298 for monosubstituted benzenes, cyclohexenes, and cyclohexanes, 24 of
      which are not in the standard reference literature. For the remaining 18 G3(MP2)
      results, the unsigned mean difference between calculated Delta(f)H298 values and
      experimental results is +/-0.91 kcal x mol(-1).

PMID- 11312943
TI  - Ion-dipole S(N)2 reaction in acetone-water mixtures. Electrostatic and specific
      solute-solvent interactions.
AB  - The rate constants of the S(N)2 reaction of sodium 4-nitrophenoxide (1) and
      iodomethane were determined by UV-visible spectrophotometry in acetone-water
      mixtures at 25, 30, and 35 degrees C. The rate-Xwater (mole fraction of water)
      profile shows that the reaction depends strongly on the medium. The fastest rate
      constant was obtained in pure acetone, and a minimum occurred at Xwater= 0.4,
      whereas the observed second-order rate constants increases again in the water
      rich region. In pure acetone, in the presence of dicyclohexano-[18]-crown-6,
      increases linearly with the concentration of the crown ether as a result of the
      complexation of the sodium ion (KS = 104.8 M) of the ion-pair and the increase in
      the effective concentration of free 4-nitrophenoxide ion, which was assumed to be
      the only reactive species. Ion-pairing was also detected at Xwater= 0.65 with a
      dissociation constant Kd = 7.82 x 10(-4) M(-1). The solvatochromic behaviors of
      2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)-1-phenoxide (2), 4-[(1-methyl-4(1H)
      pyridinylidene)ethylidene]-2,5-cyclohexadien-1-one (3), and 1-methyl-8-oxy
      quinolinium betaine (4) were investigated in the entire range of acetone-water
      mixtures. The dyes presented an increasing order of hydrophilicity compatible
      with their chemical structure, i.e., 2 < 3 < 4. Kinetic parameters for the
      methylation of 1 and the ET values of the dyes show a linear correlation of the
      polarity in the region of Xwater = 1.0-0.40 for 3 and 4, and it was observed that
      the more hydrophilic the dye the better the correlation coefficient, because of
      the structural similarity with 1. The activation parameter-Xwater profile shows
      extrema at Xwater < 0.4, reflecting an important change in the structure of the
      solvent that is responsible for the changes in the solvation of the reactive
      species including ion-pairs. These results suggest that the addition of water to
      acetone reduces abruptly the rate of substitution due to the preferential
      solvation (PS) of the phenoxide ion by the hydrogen-bonding donor (HBD) solvent.
      Nevertheless, the real second-order rate constant is "masked" by the association
      involving Na+ and 4-nitrophenoxide that extends even to water-rich mixtures. A
      model, based on the assumption that the free-energy terms involved in the second
      order rate constant and the dissociation constant of the ion-pair have two
      components, is invoked to explain the kinetic data. One of the components depends
      on electrostatic interactions for which the main variable is the dielectric
      constant of the solvent mixture, and the other depends on the specific solute
      solvent interactions, expressed by the activity coefficients of transfer of the
      species involved. The model indicates that in the range of Xwater = 1.0-0.40 the
      interactions are exclusively electrostatic, while for the rest of the acetone
      rich region they are specific with a large contribution of the 4-nitrophenoxide
      ion.

PMID- 11312944
TI  - Mimicry of peptide backbone geometry and heteroatomic side-chain functionality:
      synthesis of enantiopure indolizidin-2-one amino acids possessing alcohol, acid,
      and azide functional groups.
AB  - Indolizidinone amino acids possessing various heteroatomic side chains at their 5
      and 7-positions have been synthesized through modification of hydroxymethyl
      indolizidinone amino acids 5 and 6. Displacements of the methanesulfonates from
      alcohols 5 and 6 with sodium azide, as well as oxidation of alcohol 5, have been
      used to furnish orthogonally protected indolizidin-2-one diamino carboxylates 7
      and 8, and indolizidin-2-one amino dicarboxylate 9. Both 5- and 7
      hydroxymethylindolizidinone amino acids 5 and 6 were obtained from sequences
      commencing with the Claisen condensation of alpha-tert-butyl gamma-methyl l-N
      (PhF)-L-glutamate to furnish di-tert-butyl 4-carbomethoxy-5-oxo-2,8-di-[N
      (PhF)amino]azelate 10 (PhF = 9-(9-phenylfluorenyl)). Subsequent hydride reduction
      of 10 to an isomeric mixture of diols 12, selective protection of the primary
      alcohol as tert-butyldimethylsilyl ether 14 and oxidation of the secondary
      alcohol gave di-tert-butyl 4-tert-butyldimethylsilyloxymethyl-5-oxo-2,8-di-[N
      (PhF)amino]azelate 15 as a separable diastereomeric mixture. Linear ketone 15 and
      alcohol 14 were then converted to the indolizidinone heterocycles by routes
      featuring reductive aminations, methanesulfonate displacements, and lactam
      cyclizations. A series of rigid scaffolds designed to mimic the conformations of
      dipeptides possessing serine, lysine, and glutamate residues has thus been
      synthesized by this new route for installing heteroatomic side-chain functional
      groups onto the indolizidin-2-one system.

PMID- 11312945
TI  - Synthesis of enantiopure 7-[3-azidopyl]indolizidin-2-one amino acid. A
      constrained mimic of the peptide backbone geometry and heteroatomic side-chain
      functionality of the ala-lys dipeptide.
AB  - Enantiopure N-(BOC)amino-7-[3-azidopropyl]indolizidin-2-one acid 1 has been
      synthesized by displacement of the methanesulfonate of its 7-hydroxypropyl
      counterpart 11 with sodium azide and subsequent ester hydrolysis. N-(BOC)Amino-7
      [3-hydroxypropyl]indolizidin-2-one ester 11 was obtained from a sequence
      commencing with the alkylation of (2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N
      (PhF)amino]azelate 5 (PhF = 9-(9-phenylfluorenyl)). Stereoselective allylation of
      5, regioselective olefin hydroboration, selective primary alcohol protection as a
      silyl ether, and oxidation of the secondary alcohol gave (2S,4R,8S)-di-tert-butyl
      4-[3-tert-butyldimethylsiloxypropyl]-5-oxo-2,8-di-[N-(PhF)amino]azelate 9 as a
      pure diastereomer in 33% overall yield. Linear ketone 9 was then converted into
      the indolizidinone heterocycle by a route featuring reductive amination, lactam
      cyclization, and isolation by way of a silyl ether which provided the (6S,7R)
      isomer of 11.

PMID- 11312946
TI  - Total syntheses of five indole alkaloids from the marine bryozoan Flustra
      foliacea.
AB  - A general, efficient, and conceptually new approach to the total syntheses of
      marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2),
      (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is
      outlined. The key step in the syntheses involves the conjugated addition of an
      organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines.
      Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16%
      overall yield, respectively, whereas flustramides 3 and 4 have been synthesized
      in only four steps with 24% and 18% overall yield, respectively, on the basis of
      2-hydroxyindolenines.

PMID- 11312947
TI  - A theoretical study of the uncatalyzed and BF3-assisted Baeyer-Villiger
      reactions.
AB  - The mechanisms for the uncatalyzed and boron trifluoride (BF3) assisted Baeyer
      Villiger reactions between acetone and hydrogen peroxide have been investigated
      using high level ab initio [MP2 and CCSD(T)] and density functional theory
      (B3LYP) methods. Both steps in the uncatalyzed reaction are found to have very
      high transition state energies. It is clear that detectable amounts of the
      Crieege intermediate or the products cannot be formed without the aid of a
      catalyst. The main function of BF3 in both the addition step and the
      rearrangement (migration) step is to facilitate proton transfer. In the addition
      step the complexation of hydrogen peroxide with BF3 leads to an increased acidity
      of the attacking OH group, while in the rearrangement step BF3 takes active part
      in the proton-transfer process. This latter step is found to be rate determining
      with an activation free energy of 17.7 kcal/mol in organic solution. The products
      of the reaction are BF2OH, hydrogen fluoride, and methyl acetate. Thus, BF3 is
      not directly regenerated from the reaction.

PMID- 11312948
TI  - Reverse aromatic cope rearrangement of 2-allyl-3-alkylideneindolines driven by
      olefination of 2-allylindolin-3-ones: synthesis of alpha-allyl-3-indole acetate
      derivatives.
AB  - The reverse aromatic Cope rearrangement of 2-allyl-3-alkylideneindolines obtained
      by Horner-Wadsworth-Emmons olefination of 2-allylindolin-3-ones was performed.
      When 2-allylindolin-3-ones were treated with phosphonium ylides in refluxing
      toluene, domino Wittig reaction and reverse aromatic Cope rearrangement took
      place to give alpha-allyl-3-indole acetate derivatives in good yields. The
      aromatization as a new driving force in the Cope rearrangement is preferable to
      the conjugation with the carbonyl and cyano groups and also to the alkyl
      substitution pattern, which are well-known driving forces.

PMID- 11312949
TI  - Highly diastereofacial anti-aldol reaction: practical synthesis of optically
      active anti-2-alkyl-3-hydroxycarboxylic acid ester units.
AB  - A variety of esters derived from commercially available norephedrine were used in
      diastereoselective anti-aldol reactions. The aldol reaction of designed 2-(N-2
      methylbenzyl-N-2,4,6-trimethylbenzyl)amino-1-phenylpropanol esters 4a-d with
      aldehydes furnished anti-2-alkyl-3-hydroxycarboxylic acid esters in excellent
      diastereomeric ratios (>98:2) when LDA-Cp2ZrCl2 (0.3 equiv) was used for
      enolization, followed by transmetalation into the zirconium enolate for
      aldolization. The novel auxiliary 3 for the anti-aldol reaction does not exhibit
      the ordinary basicity of tertiary amines; 3 can be extracted from acidic media
      with organic solvents. Its use is, therefore, very advantageous not only for
      extraction of the aldol products from the acidic water solutions, but also for
      recovering the chiral auxiliary 3 after the reductive cleavage. Treatment of
      aldol or 3-protected aldol products with DIBAL-H or LiAlH4 affords the versatile
      synthons, 2-alkyl-propane-1,3-diols or those 3-protected diols in >98% ee's
      together with 3 in nearly quantitative recovery.

PMID- 11312950
TI  - Gamma-linolenic acid biosynthesis: cryptoregiochemistry of delta6 desaturation.
AB  - The valuable nutraceutical gamma-linolenic acid (GLA, (6Z,9Z,12Z)
      octadecatrienoic acid) is biosynthesized by a series of regio- and
      stereoselective dehydrogenation reactions that are catalyzed by a set of enzymes
      known as fatty acid desaturases. As part of ongoing research into the mechanism
      of these remarkable catalysts, we have examined the cryptoregiochemistry (site of
      initial oxidation) of Delta6 desaturation as it occurs in the protozoan
      Tetrahymena thermophila. Two complementary approaches that address this issue are
      described. In the first set of experiments, we measured the individual primary
      deuterium kinetic isotope effects associated with the C-H bond cleavages at C-6
      and C-7. Competition experiments using appropriately deuterium-labeled 4
      thiasubstrates revealed that a large KIE (kH/kD = 7.1 +/- 0.5) was observed for
      the C-H bond-breaking step at C-6, whereas the C-H bond cleavage at C-7 was
      insensitive to deuterium substitution (kH/kD = 1.04 +/- 0.05). These results
      point to C-6 as the site of initial oxidation in Delta6 desaturation since the
      first chemical step in this type of reaction is rupture of a strong, unactivated
      C-H bond, an energetically difficult process that typically exhibits a large KIE.
      This conclusion was supported by the results of our second approach, which
      involved locating the position of the putative diiron oxo oxidant with respect to
      substrate by monitoring the efficiency of oxo transfer to a series of thia fatty
      acid probes. Thus only a 6-thia-analogue is converted to significant amounts of
      the corresponding sulfoxide (9% yield). The absolute configuration of this
      product was determined to be S using (S)-MPAA as a chiral shift reagent. Taken
      together, these results point to the abstraction of the C-6 pro S hydrogen as the
      initial event in Delta6 desaturation as it occurs in T. thermophila.

PMID- 11312951
TI  - X-ray crystal structures and conformational analysis of bicyclo[5.3.1]undec-1(11)
      enes: twisting versus pyradidalization in anti-bredt olefins.
AB  - The synthesis of several 9,11,11-trihalo[5.3.1]propellanes and their 4
      dimethylsila analogues is described. They solvolyze under formation of the
      corresponding isomeric 7,9,11- trihalobicyclo[5.3.l]undec-1(11)-enes which are
      "anti-Bredt" olefins with a strained trans double bond in a bridged eight
      membered ring; in the presence of nucleophiles such as water or ethanol, the
      corresponding 7-hydroxy or 7-ethoxy derivatives, respectively, are obtained. On
      the basis of the X-ray crystal structures of four of these compounds (1a, 9a, 15,
      17b), the effect of strain and of the substitution pattern on the degree of
      twisting and pyramidalization of the double bond is discussed.

PMID- 11312952
TI  - Convenient formation of 4-hydroxyalk-2-en-1-one functionality via A knoevenagel
      type carbon chain elongation reaction of aldehyde with 1-arylsulfinylalkan-2-one.
AB  - A highly functionalized four-carbon unit, 4-hydroxyalk-2-en-1-one functionality
      [R2CH(OH)CH=CHCOR1], was conveniently prepared by a reaction of an aldehyde
      (R2CH2CHO) with a 1-(arylsulfinyl)alkan-2-one [ArS(O)CH2COR1] in the presence of
      diethylamine (Knoevenagel condition). Other functional groups, such as carbonyl
      and hydroxy groups, in both of the alkyl chains (R1, R2) did not prevent this
      reaction. This reaction was used to conveniently prepare (+/-)-(11E)-13-hydroxy
      10-oxooctadec-11-enoic acid (14), having cytotoxic activity, and its analogues
      from undec-10-enoic acid in good yield.

PMID- 11312953
TI  - Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by
      radical cyclization: use of glyoxylic acid hydrazone derivatives.
AB  - Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b)
      are easily esterified in high yield by beta-bromo alcohols. The resulting esters
      undergo radical cyclization to alpha-(2,2-diphenylhydrazino)- or alpha
      [(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for
      radical cyclization were also made using a beta-(phenylseleno) alcohol and an
      enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as
      effective as 2a or 2b. The imine 28 was prepared by an indirect route; it
      undergoes radical cyclization with displacement of the nitrogen substituent (28 -
      > 30) so that an alpha-amino lactone can be generated by acid hydrolysis of the
      cyclization product.

PMID- 11312954
TI  - The 1,2,4-triazolyl cation: thermolytic and photolytic studies.
AB  - The generation of the 1,2,4-triazolyl cation (1) has been attempted by the
      thermolysis and photolysis of 1-(1,2,4-triazol-4-yl)-2,4,6-trimethylpyridinium
      tetrafluoroborate (2) and the thermolysis of 1- and 4-diazonium-1,2,4-triazoles,
      using mainly mesitylene as the trapping agent. Thermolysis of 2 gave mostly 1,2,4
      triazole, together with 3-(1,2,4-triazol-4-yl)-2,4,6-trimethylpyridine, 4-(1,2,4
      triazol-4-ylmethyl)-2,6-dimethylpyridine, and 4-(2,4,6-trimethylbenzyl)-2,6
      dimethylpyridine. Thermolysis of each of the diazonium salts in the presence of
      mesitylene again gave mainly triazole together with very low yields of 1-(1,2,4
      triazol-1-yl)-2,4,6-trimethylbenzene and the corresponding -4-yl isomer in about
      the same ratio. On the other hand, photolysis of 2 in mesitylene gave mainly 1
      (1,2,4-triazol-1-yl)-2,4,6-trimethylbenzene. A photoinduced electron transfer
      from mesitylene to 2 has been observed and preliminary laser flash photolyses of
      2 and the corresponding 2,4,6-triphenylpyridinium salt have been carried out. The
      observed transients are explained as arising from the first excited states of the
      pyridinium salts rather than from 1. Ab initio MO calculations are reported and
      indicate that the predicted electronic ground-state of the triazolyl cation is a
      triplet state of B1 symmetry with five pi electrons, which corresponds to a
      diradical cation (1c). Possible mechanisms for the formation of the various
      products are proposed.

PMID- 11312955
TI  - Regio- and stereoselectivity of captodative olefins in 1,3-dipolar
      cycloadditions. A DFT/HSAB theory rationale for the observed regiochemistry of
      nitrones.
AB  - Captodative olefins 1-acetylvinyl carboxylates proved to be highly regioselective
      dipolarophiles in 1,3-dipolar cycloadditon to propionitrile oxide,
      arylphenylnitrile imines, diazoalkanes, and nitrones to yield the corresponding 5
      substituted heterocycles. The addition of the latter was also stereoselective,
      being slightly susceptible to steric demand of the carboxylate substituent in the
      olefin. All atempts to cleave the isoxazolidine N-O bond under reductive
      conditions failed, providing diverse products with side-group reduction. FMO
      theory was unsuccessful to explain the regioselectivity observed with nitrones,
      since the opposite orientation was predicted. The recently formulated DFT/HSAB
      theoretical model was able to rationalize this regioselectivity, identifying the
      nucleophilic and electrophilic atoms involved in the process via calculation of
      interaction energies, suggesting the specific direction of the electronic process
      at each of the reaction sites.

PMID- 11312956
TI  - Entropy-controlled selectivity in the vinylation of a cyclic chiral nitrone. An
      efficient route to enantiopure polyhydroxylated pyrrolidines.
AB  - A short synthesis of 1,4-dideoxy-1,4-imino-L-arabinitol (LAB1) (4) and of 1,4
      dideoxy-1,4-imino-D-galactitol (5), two azasugars active as enzymatic inhibitors,
      is reported. The key reaction is the addition of vinylmagnesium chloride to
      (3S,4S)-3,4-bis(benzyloxy)-3,4-dihydro-2H-pyrrole 1-oxide (3), a nitrone easily
      available from L-tartaric acid. Unexpectedly, the reaction affords the
      corresponding (2S,3S,4S)-1-hydroxy-2-ethenyl-3,4-bis(benzyloxy)pyrrolidine (9) in
      very good yield and in 93/7 diastereomeric ratio (dr) independently of the
      reaction temperature, thus representing a unique case of entropy-controlled
      reaction in a 100 K interval (from +20 degrees C to -80 degrees C). The trans
      intermediate 9 is converted in two steps (reduction, N-protection) into the
      common intermediate (2S,3S,4S)-1-(benzyloxycarbonyl)-3,4-bis(benzyloxy)-2
      ethenylpyrrolidine (11). Double bond oxidation followed by reductive
      debenzylation opens a route to the target pyrrolidine azasugars 4 and 5.

PMID- 11312957
TI  - Simple and efficient preparation of [10,20-13C2]- and [10-CH3,13-13C2]-10
      methylretinal: introduction of substituents at the 2-position of 2,3-unsaturated
      nitriles.
AB  - In this paper, we present the synthesis of [10,20-13C2]-10-methylretinal and [10
      CH3,13-13C2]-10-methylretinal, two doubly 13C-labeled chemically modified
      retinals that have been recently used to study the structural and functional
      details behind the photocascade of bovine rhodopsin (Verdegem et al. Biochemistry
      1999, 38, 11316; de Lange et al. Biochemistry 1998, 37, 1411). To obtain both
      doubly 13C-labeled compounds, we developed a novel synthetic method to directly
      and regiospecifically introduce a methyl substituent on the 2-position of 3
      methyl-5-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-2,4-pentadienenitrile.
      Encouraged by these results, we investigated the scope of this novel reaction by
      developing a general method for the introduction of a variety of substituents to
      the 2-position of 3-methyl-2,3-unsaturated nitriles, paving the way for simple
      and efficient synthesis of a wide variety of 10-, 14-, and 10,14-substituted
      chemically modified retinals, and other biologically important compounds.

PMID- 11312958
TI  - Aluminum-controlled reactivity and diastereoselectivity toward radical reactions
      of optically active aldimines with metallic samarium.
AB  - The intermolecular pinacol-type coupling reaction and allylation reaction of
      optically active imines bearing a beta-hydroxy group were performed
      stereoselectively with metallic samarium after treatment of the imines with
      trimethylaluminum.

PMID- 11312959
TI  - Studies in polyphenol chemistry and bioactivity. 3.(1,2) stereocontrolled
      synthesis of epicatechin-4alpha,8-epicatechin, an unnatural isomer of the B-type
      procyanidins.
AB  - Oligomeric procyanidins containing 4alpha-linked epicatechin units are rare in
      nature and have hitherto not been accessible through stereoselective synthesis.
      We report herein the preparation of the prototypical dimer, epicatechin-4alpha,8
      epicatechin (6), by reaction of the protected 4-ketones 11a,b with aryllithium
      reagents derived by halogen/metal exchange from the aryl bromides 26a,b. Removal
      of the 4-hydroxyl group from the resulting tertiary benzylic alcohols 27a,b was
      effected by tri-n-butyltin hydride and trifluoroacetic acid in a completely
      stereoselective manner, resulting in hydride delivery exclusively from the beta
      face. If benzyl was chosen for protection of the 3-hydroxyls, all protective
      groups could subsequently be removed in a single step by hydrogenolysis. tert
      Butyldimethylsilyl groups, on the other hand, permitted selective deprotection of
      the 3-hydroxyls in preparation for their subsequent acylation with tri-O
      benzylgalloyl chloride. Only monogalloylation at the "bottom" 3-hydroxyl took
      place when 28c was acylated under the previously reported conditions, reflecting
      the increased steric hindrance of the "top" 3-hydroxyl group in 28c compared with
      its 4beta,8-isomer 3. The preparation of compounds 14 and 17 containing
      phloroglucinol trimethyl ether in the 4alpha and 4beta linkages to epicatechin is
      also described. The 8-position of the bromine atom in 19, previously conjectured
      in analogy to the structurally characterized tetramethyl ether 20, was confirmed
      by transformation of both compounds into the common derivative 25.

PMID- 11312960
TI  - Total synthesis of the calphostins: application of fischer carbene complexes and
      thermodynamic control of atropisomers.
AB  - The total syntheses of the potent protein kinase C inhibitors calphostins A, B,
      C, and D as well as a variety of structural analogues are reported. An
      aminobenzannulation reaction of an enantiopure chromium Fischer carbene complex
      is utilized to prepare a pentasubstituted naphthylamine. After optimization of
      side-chain substituents, conversion of the naphthylamine to an o-naphthoquinone
      was followed by biomimetic oxidative dimerization using trifluoroacetic acid and
      air yielding a 1:2 P/M mixture of atropisomeric perylenequinones. Thermal
      equilibration to a 3:1 P:M atropisomeric ratio and separation of the
      perylenequinones followed by side chain desymmetrization and functionalization
      led to the total synthesis of enantio- and diastereomerically pure calphostin C
      in only twelve steps from commercially available starting materials. In addition,
      calphostins A, B, D, and several structural analogues were prepared to evaluate
      biological activities.

PMID- 11312961
TI  - Synthesis and reactions of some heterocyclic azacyanines.
AB  - The one-step reaction of some amino-substituted heterocycles with diiodomethane
      to give azacyanines is reported. This useful reaction is of wider application
      than initially reported and includes the synthesis of new substituted pyrido-,
      isoquino-, benzimadazo-, and benzothiazoazacyanines 7. Furthermore, treatment of
      these azacyanines with base generally affects a facile opening of the
      dihydrotriazinium ring resulting in the formation of new heterocycles 10, 11, and
      12, which would be difficult to prepare by other means. This reaction takes an
      additional direction in the case of halo-substituted azacyanines 7b/c/d where
      treatment with base gives rise to new interesting derivatives of
      dipyridotriazines 14b/c/d.

PMID- 11312962
TI  - A simple and efficient approach for the synthesis of fluorinated and
      nonfluorinated octaethylporphyrin-based benzochlorins with variable
      lipophilicity, their in vivo tumor uptake, and the preliminary in vitro
      photosensitizing efficacy.
AB  - Starting from commercially available Ni(II)octaethylporphyrin (OEP), an efficient
      approach for the preparation of a series of fluorinated and nonfluorinated
      benzochlorins with variable lipophicity has been developed. Their spectroscopic
      properties, preliminary in vitro photosensitizing efficacy, and tumor selectivity
      were determined. Our methodology provides a facile approach for the preparation
      of the free-base and the related Zn(II) benzochlorins containing alkyl and alkyl
      ether side chains with variable carbon units. For the preparation of
      benzochlorins containing alkyl groups attached to the exocyclic phenyl ring, the
      Ni(II) meso-(2-formylvinyl)octaethyl porphyrin 2 was reacted with various
      reagents such as (trifluoromethyl)trimethylsilane (TMS-CF3) or the Grignard
      reagents of various fluorinated or nonfluorinated alkyl halides. The
      corresponding intermediates 3, 6a-6e, and 8 obtained via intramolecular
      cyclization under acidic conditions afforded the related benzochlorins 5, 7a-d,
      and 9 in good yields except for 7e which was obtained in poor yield (11.4%). The
      alcohol 10 obtained by reacting porphyrin 2 with ethynylmagnesium chloride did
      not produce the expected acetylenic benzochlorin; instead the corresponding
      acetyl derivative 11 was obtained as a major product, which under appropriate
      reaction conditions was converted into a series of alkyl ether derivatives 13a
      13d. To obtain a benzochlorin bearing an ester functionality (15), porphyrin 2
      was first reacted with ethyl acetate/LDA and the intermediate alcohol 14 was then
      cyclized with sulfuric acid. Unlike most of the natural and synthetic chlorins,
      the Zn(II) complexes of the benzochlorin analogues exhibited a significant
      bathochromic shift ( approximately 10 nm) in the electronic absorption spectra,
      and the long wavelength absorptions were observed in the range 671-677 nm
      (epsilon: 43270-50360). For investigating the in vitro efficacy of these
      analogues, Molt-4 cells were used. At a concentration of 2.5 microM, and a light
      dose of 4 J/cm2, all benzochlorins produced significant photosensitizing
      efficacy. The tumor (RIF) and muscle uptake in C3H mice of these photosensitizers
      was determined by in vivo reflectance spectroscopy. These results indicate that
      in this series increasing the length of the alkyl or alkyl ether carbon chains at
      the fused phenyl ring system produced a significant increase in tumor uptake.

PMID- 11312963
TI  - Five-membered ring analogues of shikimic acid.
AB  - Shikimate and other intermediates of the shikimate-chorismate pathway are densely
      functionalized structures that seem to offer limited options for skeletal
      modification. We designed and synthesized cyclopentylidenes 1 and 2, as well as
      cyclopentenes 3 and 4, as novel ring-contracted analogues of shikimic acid.
      Enzymatic studies showed that analogues 1-3 are indeed processed by shikimate
      kinase to give phosphates 1-P, 2-P, and 3-P as five-membered ring analogues of
      shikimate-3-phosphate. In particular, analogue 1 is converted by the enzyme at a
      rate only 3.5-fold slower than that of the native substrate, while analogue 3
      binds to shikimate kinase with an apparent Km of 1.7 mM, compared to 0.14 mM for
      shikimate.

PMID- 11312964
TI  - The C-N rotation barrier of the lithium enolate of acetamide: an ab initio and
      density functional theory investigation.
AB  - Semiempirical (PM3), ab initio (HF/6-31+G(d) and MP2/6-31+G(d)), and density
      functional (pBP/DN) calculations are used to investigate the rotation barrier of
      the carbon-nitrogen bond in a simple enolate anion: lithium acetamide, 1. For
      comparison, the amidate anion 2, vinylamine 3, and a simulated dimer 4 were also
      calculated. In all systems, the barrier to rotation was found to be less than 10
      kcal x mol(-1) in agreement with experiment. The correlated calculations show the
      barrier to be lowest for the anion 2. The results show conjugation effects in 1
      and 2 comparable to that in vinylamine 3 and imply that polarization effects are
      more important than charge transfer in amine conjugation.

PMID- 11312965
TI  - Michael addition reactions between chiral Ni(II) complex of glycine and 3-(trans
      enoyl)oxazolidin-2-ones. A case of electron donor-acceptor attractive interaction
      controlled face diastereoselectivity.
AB  - This study has demonstrated that the readily available and inexpensive 3-(trans
      3'-alkyl/arylpropenoyl)oxazolidin-2-ones, featuring high electrophilicity and
      conformational homogeneity, are synthetically superior Michael acceptors over the
      conventionally used alkyl enoylates, allowing for a remarkable improvement in
      reactivity and, in most cases, diastereoselectivity of the addition reactions
      with a Ni(II) complex of the chiral Schiff base of glycine with (S)-o-[N-(N
      benzylprolyl)amino]benzophenone. Kinetically controlled diastereoselectivity in
      the corresponding Michael addition reactions between the Ni(II) complex of
      glycine and the oxazolidin-2-ones was systematically studied as a function of
      steric, electronic, and position effects of the substituents on the starting
      Michael acceptor. In both aliphatic and aromatic series the simple
      diastereoselectivity was found to be virtually complete, affording the products
      via the corresponding TSs with the approach geometry like. The face
      diastereoselectivity of the reactions between the Ni(II) complex of glycine and
      the 3-(trans-3'-alkylpropenoyl)oxazolidin-2-ones was found to depend exclusively
      on the steric bulk of the alkyl group on the starting Michael acceptor. In
      contrast, the face diastereoselectivity in the reactions of aromatic oxazolidin-2
      ones with the Ni(II) complex of glycine was shown to be controlled predominantly
      by the electronic properties of the aryl ring. In particular, the additions of
      the Ni(II) complex of glycine with 3-(trans-3'-arylpropenoyl)oxazolidin-2-ones,
      bearing electron-withdrawing substituents on the phenyl ring, afforded the
      (2S,3R)-configured products with synthetically useful diastereoselectivity and in
      quantitative chemical yields, thus allowing for an efficient access to the
      sterically constrained beta-aryl-substituted pyroglutamic and glutamic acids.

PMID- 11312966
TI  - Rapid and stereocontrolled synthesis of racemic and optically pure highly
      functionalized pyrrolizidine systems via rearrangement of 1,3-dipolar
      cycloadducts derived from 2-azetidinone-tethered azomethine ylides.
AB  - This work describes a convenient procedure for the straightforward preparation of
      polyfunctionalized enantiopure pyrrolizidine systems. The methodology capitalizes
      on a HCl(g)-promoted reaction of the 1,3-dipolar cycloadducts derived from 2
      azetidinone-tethered azomethine ylides, smoothly affording different types of
      highly functionalized bi- and tricyclic systems in racemic and optically pure
      forms. This process involves a selective bond cleavage of the four-membered ring,
      followed by a rearrangement under the reaction conditions. The synthetic route
      employed was shown to be compatible with a variety of 4-oxoazetidine-2
      carbaldehydes, alpha-amino esters, or dipolarophiles, offering a versatile entry
      to pyrrolizidine systems.

PMID- 11312967
TI  - Copper(II)-mediated oxidative coupling of 2-aminonaphthalene homologues.
      Competition between the straight dimerization and the formation of carbazoles.
AB  - Whereas the Cu(II)-mediated oxidative coupling of 2-aminonaphthalenes 7a and 7b
      results in the clean formation of 1,1'-binaphthyls 13a and 13b, respectively,
      their higher homologues and congeners 8-12 have been found to exhibit a different
      reaction pattern. Thus, 2-aminoanthracene (8) gave a approximately 1:1 mixture of
      the expected bianthryl derivative 15 and the carbazole 16, whereas the 9
      aminophenanthrene (10), 3-phenyl-1-aminonaphthalene (11), and 2-aminochrysene
      (12) produced almost exclusively the corresponding carbazoles 19, 20, and 21,
      respectively. By contrast, the isomeric 3-aminophenanthrene (9) gave rise to the
      azo compound 17 as a result of the preferential oxidation on the nitrogen. The
      carbazoles have been shown to arise directly from the coupling reactions rather
      than from the primarily formed binaphthyls. Alternatively, carbazole 19 can also
      be prepared from 1b on reaction with hydrazine. On the other hand, treatment of
      3a with hydrazine resulted in the formation of a approximately 2:7 mixture of
      amine 11 and arylhydrazine 22. 2,2'-Diamino-1,1'-bianthryl (15) has been resolved
      into enantiomers via cocrystallization with (-)-N-benzylcinchonidinium chloride
      and shown to have (R)-(-)-15 configuration by X-ray crystallography.

PMID- 11312968
TI  - Carbohydrate-based receptors with multiple thiourea binding sites. Multipoint
      hydrogen bond recognition of dicarboxylates and monosaccharides.
AB  - The binding properties of multitopic sugar thiourea receptors toward
      dicarboxylate and monosaccharide guests have been examined taking glutarate and
      octyl beta-D-glucopyranoside as model ligands. For the anionic hydrogen bond
      acceptor, both the complex stoichiometry and the association constants (K(as))
      were found to be strongly dependent on the relative disposition of recognition
      elements in the host. In contrast, for the glucoside guest a 1:1 stoichiometry
      was observed in all cases, the K(as) values being largely independent of the
      unbound state provided that geometrically equivalent supramolecular topologies
      can be achieved.

PMID- 11312969
TI  - Synthesis of a C1-C21 subunit of the protein phosphatase inhibitor tautomycin: a
      formal total synthesis.
AB  - The synthesis of a C1-C21 subunit of tautomycin is described. The convergent
      route employs enantioenriched allenylstannane and zinc reagents derived from (S)
      3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde
      segments to yield syn and anti adducts with high diastereoselectivity. The
      derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2C=O, to
      afford an intermediate ketone which is converted to the core spiroketal moiety of
      tautomycin upon acid treatment. Chain elongation by another addition of the
      aforementioned allenylzinc reagent to a spiroketal aldehyde proceeds with high
      diastereoselectivity to install the remaining stereocenters. The resulting
      homopropargylic alcohol adduct is converted to a methyl ketone through
      intramolecular hydrosilylation of the alkyne and Tamao oxidation of the derived
      five-membered siloxane. This ketone proved identical to an intermediate employed
      by Chamberlin in a prior total synthesis of tautomycin.

PMID- 11312970
TI  - C-glycosides to fused polycyclic ethers. A formal synthesis of (+/-)
      hemibrevetoxin B.
AB  - This paper describes a formal total synthesis of the marine ladder toxin
      hemibrevetoxin B from Danishefsky's dienes. This approach couples the generation
      of C-glycosides from cyclic enol ethers with metathesis or acid-mediated
      annulation reactions. The result is a highly efficient synthesis of the
      tetracyclic ring system of hemibrevetoxin B.

PMID- 11312971
TI  - Tandem addition beta-lithiation-alkylation sequence on alpha,beta-unsaturated
      aldehydes.
AB  - A tandem reaction between (E)-cinnamaldehyde, 1a, and phenyllithium affording
      beta-substituted dihydrochalcones was recently reported. NMR spectroscopic
      studies on the reaction mixture, as well as isotopic exchange reactions and
      trapping of two intermediates, provide clues on the several mechanistic steps of
      this new reaction. Extended studies revealed that beta-alkyl-substituted
      alpha,beta-unsaturated aldehydes and aliphatic lithium reagents did not afford
      good yields of the tandem reaction products, while aromatic lithium reagents gave
      good results. The aggregation features of the aryllithium reagents and the
      extended charged delocalization effects are considered to promote beta
      selectivity. This approach provides a convenient route for the synthesis of a
      wide variety of beta-alkyl-substituted dihydrochalcones.

PMID- 11312972
TI  - Synthesis of polycyclic structures by the Diels-Alder reaction of inner-outer
      ring 1,3-bis(trimethylsilyloxy)dienes.
AB  - A Diels-Alder reaction of novel inner-outer-ring 1,3-silyloxydienes 5-8 with a
      variety of dienophiles to afford highly functionalized polycyclic structures is
      reported. The inner-outer-ring 1,3-silyloxydienes 5-8 containing five- to seven
      membered carbocyclic and heterocyclic rings were prepared in a single reaction
      vessel from 2-acetylcyclocarbonyls in quantitative yields. The Diels-Alder
      reaction with 1,4-benzoquinone (BQ), dimethyl acetylenedicarboxylate (DMAD), and
      methyl vinyl ketone (MVK) proceeded smoothly at room temperature, affording
      functionalized polycyclic naphthols, phenols, and enones with high
      regioselectivity and good yields (39-75%). Moreover, dienes 5-8 also reacted in a
      hetero-Diels-Alder reaction with benzaldehyde (BA) and N-benzylideneaniline (NBA)
      in the presence of catalytic amounts of ZnCl2, affording substituted polycyclic
      pyranones and pyridinones in good yields (40-93%). Overall, our synthetic
      strategy provides straightforward access to an interesting set of polycyclic
      structures useful for natural and nonnatural product synthesis.

PMID- 11312973
TI  - Synthesis of 2,3-dihydroindoles, indoles, and anilines by transition metal-free
      amination of aryl chlorides.
AB  - Aliphatic and aromatic amines react with 2- and 3-chlorostyrene in the presence
      of potassium tert-butoxide to give N-substituted 2,3-dihydroindoles in good
      yields. The combination of this domino-amination protocol with a suitable
      dehydrogenation reaction gives access to pharmacologically interesting indoles in
      a one-pot procedure. Overall product yields of N-substituted indoles >50% are
      obtained by this method starting from commercially available substrates. In
      addition to the intramolecular base-promoted amination of aromatic C-Cl bonds,
      metal-free intermolecular aminations of aryl chlorides with primary and secondary
      amines are described. The use of potassium tert-butoxide as base allows the
      synthesis of various anilines in good to excellent yields. Due to the formation
      of aryne intermediates, either N-substituted anilines or meta-substituted
      anilines are produced with excellent selectivities.

PMID- 11312974
TI  - Asymmetric synthesis of 2-alkyl-perhydroazepines from [5,3,0]-bicyclic lactams.
AB  - The synthesis and utility of a novel class of [5,3,0]-bicyclic lactams are
      described. Produced by the cyclodehydration of (R)-phenylglycinol with omega-keto
      acids, lactams 4-6 were obtained as separable diastereomeric mixtures (
      approximately 2:1) in low yields ( approximately 40%). Higher chemical yield (up
      to 61%) was realized via an alternate route involving ring closure metathesis of
      2-allyl-N-acroyl oxazolidines, 8. Stereoselective reductions of the syn-bicyclic
      lactams, 4a and 5a, occurred with the use of alane or lithiumaluminum hydride,
      affording azepine alcohols, 11a and 15a, of the R configuration at the 2
      position, in good to moderate yields (50-88%). High selectivity was also observed
      in the diisobutylaluminum hydride reduction of the epimeric anti lactams, 4b and
      5b, affording azepine alcohols, 11b and 15b, of the S configuration at C-2.
      Hydrogenolytic cleavage of the N-benzyl moiety afforded chiral 2-substituted
      perhydroazepines, (R)- and (S)-12, in good yields and good enantiomeric excesses
      (84-94%).

PMID- 11312975
TI  - Beta-hydroxy-gamma-lactones as chiral building blocks for the enantioselective
      synthesis of marine natural products.
AB  - The enantioselective synthesis of trans-(+)-laurediol, (2S,3S,5R)-5-[(1R)-1
      hydroxy-9-decenyl]-2-pentyltetrahydro-3-furanol, and (2S,3S,5S)-5-[(1S)-1-hydroxy
      9-decenyl]-2-pentyltetrahydro-3-furanol are described. In addition, a formal
      synthesis of trans-(-)-kumausyne is also developed. All the synthetic procedures
      have in common the use of enantiomerically enriched beta-hydroxy-gamma-lactones,
      easily available by Sharpless asymmetric dihydroxylation (AD) from the suitable
      beta,gamma-unsaturated ester. The use of Katsuki-Sharpless asymmetric epoxidation
      (AE) as an additional enantioselective reaction provides cyclic compounds of high
      enantiomeric purity.

PMID- 11312976
TI  - Total synthesis of natural dysidiolide.
AB  - Dysidiolide (1), a novel sesterterpenoid previously isolated from the Caribbean
      sponge Dysidea etheria de Laubenfels, inhibits the action of the protein
      phosphatase, cdc25A. The authors establish a novel total synthesis of natural
      dysidiolide (1) using intramolecular Diels-Alder reaction as the key step from
      optically active cyclohexenone 3. Decalin, the core structure of 1, was
      constructed by intramolecular Diels-Alder reaction of the diene ester generated
      by elimination of the phenyl sulfoxide group from sulfoxide ester 6 prepared from
      cyclohexenone 3. Diastereoselective methylation at C-7, alkylation at C-6, and
      deoxygenation of C-12 and C-24 positions gave the fully substituted bicyclic core
      of 1. The two side chains of the bicyclic core were further extended so as to
      afford natural dysidiolide (1). The total yield of this synthesis exceeds that of
      previous syntheses of 1.

PMID- 11312977
TI  - Diketo compounds with (trifluoromethyl)trimethylsilane: double nucleophilic
      trifluoromethylation reactions.
AB  - Reactions of various diketo compounds with (trifluoromethyl)trimethylsilane
      (Me3SiCF3) in the presence of catalytic amounts of cesium fluoride have been
      studied. gamma-Ketoesters, CH3COCH2CH2CO2R (R = Et, Bu), were reacted with 2
      equiv of Me3SiCF3 at room temperature to give CH3C(OH)(CF3)CH2CH2COCF3 in good
      yield after hydrolysis. alpha-Diketones, R1COCOR2 (R1 = R2 = Ph; R1 = Ph, R2 =
      Me; R1 = R2 = Me; R1 = Me, R2 = Et), when reacted with Me3SiCF3, formed 1:1 or
      1:2 addition products depending on the reaction conditions and stoichiometry
      used. Reactions of diones CH3COXCOCH3 (X = -CH2CH2-, -C6H4C6H4-, -CH2-) with
      Me3SiCF3 also led to the formation of the mono- or diaddition products depending
      on reaction conditions. With various kinds of substituted arylglyoxals, 2 equiv
      of Me3SiCF3 produced monoaddition products in 70-75% yield and diaddition
      products in 5-10% yield. One of the monoalcohols and two of the diols have been
      characterized by single-crystal X-ray analysis, and the presence of inter- and
      intramolecular hydrogen bonding has been confirmed.

PMID- 11312978
TI  - Asymmetric hydrosilylation of styrenes catalyzed by palladium-MOP complexes:
      ligand modification and mechanistic studies.
AB  - In the palladium-catalyzed asymmetric hydrosilylation of styrene (3a) with
      trichlorosilane, several chiral monophosphine ligands, (R)-2-diarylphosphino-1,1'
      binaphthyls (2a-g), were examined for their enantioselectivity. The highest
      enantioselectivity was observed in the reaction with (R)-2-bis[3,5
      bis(trifluoromethyl)phenyl]phosphino-1,1'-binaphthyl (2g), which gave (S)-1
      phenylethanol (5a) of 98% ee after oxidation of the hydrosilylation product, 1
      phenyl-1-(trichlorosilyl)ethane (4a). The palladium complex of 2g also
      efficiently catalyzed the asymmetric hydrosilylation of substituted styrenes on
      the phenyl ring or at the beta position to give the corresponding chiral benzylic
      alcohols of over 96% ee. Deuterium-labeling studies on the hydrosilylation of
      regiospecifically deuterated styrene revealed that beta-hydrogen elimination from
      1-phenylethyl(silyl)palladium intermediate is very fast compared with reductive
      elimination giving hydrosilylation product when ligand 2g is used. The reaction
      of o-allylstyrene (9) with trichlorosilane catalyzed by (R)-2g/Pd gave (1S,2R)-1
      methyl-2-(trichlorosilylmethyl)indan (10) (91% ee) and (S)-1-(2-(propenyl)phenyl)
      1-trichlorosilylethanes (11a and 11b) (95% ee). On the basis of their opposite
      configurations at the benzylic position, a rationale for the high
      enantioselectivity of ligand 2g is proposed.

PMID- 11312979
TI  - Comparison between electron transfer and nucleophilic reactivities of ketene
      silyl acetals with cationic electrophiles.
AB  - The products and kinetics for the reactions of ketone silyl acetals with a series
      of p-methoxy-substituted trityl cations have been examined, and they are compared
      with those of outer-sphere electron transfer reactions from 10,10'-dimethyl-9,9',
      10, 10'- tetrahydro-9,9'-biacridine [(AcrH)2] to the same series of trityl
      cations as well as other electron acceptors. The C-C bond formation in the
      reaction of beta,beta-dimethyl-substituted ketene silyl acetal (1:
      (Me2C=C(OMe)OSiMe3) with trityl cation salt (Ph3C+ClO4-) takes place between 1
      and the carbon of para-positon of phenyl group of Ph3C+, whereas a much less
      sterically hindered ketene silyl acetal (3: H2C=C(OEt)OSiEt3) reacts with Ph3C+
      at the central carbon of Ph3C+. The kinetic comparison indicates that the
      nucleophilic reactivities of ketene silyl acetals are well correlated with the
      electron transfer reactivities provided that the steric demand at the reaction
      center for the C-C bond formation remains constant.

PMID- 11312980
TI  - Oxidative transformation of tert-cyclobutanols by palladium catalysis under
      oxygen atmosphere.
AB  - Palladium(II)-catalyzed oxidative reaction of tert-cyclobutanols involving the
      cleavage of a C-C bond via beta-carbon elimination under atmospheric pressure of
      oxygen is described. An alkylpalladium intermediate produced by beta-carbon
      elimination from a Pd(II) alcoholate gives a variety of products, depending on
      the substituents on the cyclobutane ring, in which reactions such as
      dehydrogenative ring opening, ring expansion and ring contraction are involved.
      For some substrates, the addition of a catalytic amount of ethyl acrylate
      dramatically accelerates the reaction. In all cases, the dehydrogenative products
      are obtained and the Pd(II)-hydride species produced at the final stage can be
      converted again to active Pd(II) species by molecular oxygen.

PMID- 11312981
TI  - On the direction and magnitude of radical substituent effects: the role of polar
      interaction on thermodynamic stabilities of benzylic C-H bonds and related carbon
      radicals.
AB  - The C-H bond dissociation enthalpies (BDEs) of polarized benzylic molecules,
      i.e., para-substituted phenylacetonitriles (PANs), and the spin variations of the
      radicals of the general type p-GC6H4CH*-Y were investigated using density
      functional theory (DFT) calculations. In contrast to the commonly observed S-type
      substituent effect (see text), the present work shows that there should be three
      (rather than one) primary patterns (i.e., S, O, and counter-O) for remote G to
      affect spin and radical stability, depending upon the polarity of the alpha-Y
      group. Correlation analyses reveal that both the direction and magnitude of
      spin/radical effects are quantitatively related to the intensity of polar
      interaction in radical system, as registered by either the calculated group
      charges of the phenyl ring (C(Ph)) or by the polar constant sigma(+)s (Figures 1
      4). A unified platform (Scheme 1) to rationalize the apparent differences of
      radical substituent effect is proposed.

PMID- 11312982
TI  - Synthesis of hexahomotrioxacalix[3]naphtalenes and a study of their alkali-metal
      cation binding properties.
AB  - The first syntheses of the C3-symmetrical and unsymmetrical
      hexahomotrioxacalix[3]naphthalenes 3 and 4, respectively, and the corresponding
      tert-butyl hexahomotrioxacalix[3]naphthalene 3a are reported. A convergent
      synthesis of the linear hexahomotrimer precursors 19 and 19a is described, but
      the direct synthesis of 3 and 3a can also be achieved from the monomers 20 and
      20a, respectively. A limited study of the binding properties of alkali-metal
      cations by 3 or 3a using a picrate-CHCl3 extraction showed only weak abilities to
      bind with the cations examined.

PMID- 11312983
TI  - Reactions of 1,2-oxaphospholenes. 9. Attempted deprotonation at C5.

PMID- 11312985
TI  - Unusual oxidative bond-forming reactions upon 1,4-dihydropyridines:
      manganese(III)-promoted, single- and double-malonate additions.

PMID- 11312984
TI  - Facile C1 Epimerization of alpha-1-sulfonamidyl-2-deoxy-2-iodo- glycopyranosides.

PMID- 11312986
TI  - On the reaction of sodium methoxide with perbromo-D2h-bishomocubane. A structural
      reassignment.

PMID- 11312988
TI  - New parent homooxacalixarenes through thermal dehydration of a
      bishydroxymethylated triphenol.

PMID- 11312987
TI  - Enantioselective synthesis of (R)- and (S)-4-benzyloxy-2-cyclohexen-1-one.

PMID- 11312989
TI  - Palladium-catalyzed selective cross-coupling between 2-bromopyridines and aryl
      bromides.

PMID- 11312990
TI  - Domino carbocationic rearrangement of alpha-[bis(methylthio)methylene]alkyl-2
      aryl-cyclopropyl carbinols; facile access to 1-arylindanes.

PMID- 11312991
TI  - Stereocontrolled conversion of quinine into 10(R),11-dihydroxydihydroquinine via
      the sharpless osmylation process.

PMID- 11312992
TI  - Boradiazaindacene-appended calix[4]arene: fluorescence sensing of pH near
      neutrality.

PMID- 11312993
TI  - A convenient synthetic route to (Sp)-methylphosphine borane derivatives via an
      asymmetric lithiation/trapping-reductive elimination strategy.

PMID- 11312994
TI  - Effect of supramolecular inclusion on the selectivity of 3-nortricyclanylidene.

PMID- 11312995
TI  - Oxidative cleavage of 1,3-dicarbonyls to carboxylic acids with oxone.

PMID- 11312996
TI  - Synthesis of 1,2,3,4,5,6,7,8-octahydroacridine via condensation of cyclohexanone
      with formaldehyde.

PMID- 11312997
TI  - The [Cu(OH).TMEDA]2Cl2-catalyzed coupling of arylboronic acids with imidazoles in
      water.

PMID- 11313000
TI  - Drug interaction: omeprazole and phenprocoumon.
AB  - BACKGROUND: Oral anticoagulants like the coumarin derivatives are characterised
      by a particularly narrow therapeutic range. Any interfering co-medication can
      pose a challenge to establishing a stable anticoagulant dosage regimen and thus
      present a serious risk for the patient. Here we describe two cases of patients on
      anticoagulant therapy that suggest possible drug interactions between
      phenprocoumon and the proton pump inhibitor omeprazole. RESULTS: In both
      patients, the International Normalised Ratio (INR) increased beyond the
      therapeutic range after they were given omeprazole for the treatment of
      gastrointestinal symptoms. The INR returned to therapeutic levels after the
      phenprocoumon dose was reduced (Case 1) and omeprazole discontinued (Case 2).
      CONCLUSIONS: The increased anticoagulant activity of phenprocoumon observed in
      the two described cases and the known interaction potential of omeprazole suggest
      that the clearance of phenprocoumon may have been reduced due to competitive
      inhibition of its degradation by omeprazole. Drug interactions may be one of the
      reasons for the difficulties encountered with some patients in establishing a
      stable anticoagulant therapy. Physicians should carefully review any concurrently
      used medication and if possible opt for drugs with a low interaction potential.

PMID- 11312999
TI  - Thyroxine signal transduction in liver cells involves phospholipase C and
      phospholipase D activation. Genomic independent action of thyroid hormone.
AB  - BACKGROUND: Numerous investigations demonstrate a novel role of thyroid hormone
      as a modulator of signal transduction. Protein kinase C (PKC) is critical to the
      mechanism by which thyroid hormones potentiate both the antiviral and
      immunomodulatory actions of IFNgamma in different cells and regulate the exchange
      of signalling phospholipids in hepatocytes. Because nothing is known about
      accumulation of PKC modulator - diacylglycerol in cells treated with T4, we
      examined the nongenomic effect of thyroid hormones on DAG formation and
      phospholipase activation in liver cells. RESULTS: The results obtained provide
      the first demonstration of phospholipase C, phospholipase D and protein kinase C
      nongenomic activation and diacylglycerol (DAG) accumulation by L-T4 in liver
      cells. The experiments were performed in either the [14C]CH3COOH-labeled rat
      liver slices or isolated hepatocytes pre-labeled by [14C]oleic acid. L-T4
      activates the DAG production in a concentration- and time-dependent manner. DAG
      formation in stimulated cells is biphasic and short-lived event: there is an
      initial, rapid rise in DAG concentration and then a slower accumulation that can
      be sustained for a few minutes. The early phase of L-T4 generated DAG only is
      accompanied by phosphatidylinositol 4,5-bisphosphate level decrease and inositol
      1,4,5-trisphosphate formation while the second phase is abolished by PKC
      inhibitor l,(5-isoquinolinesulphonyl)2methylpiperasine dihydrochloride (H7) and
      propranolol. The second phase of DAG production is accompanied by free choline
      release, phosphatidylcholine content drop and phosphatidylethanol (Peth)
      formation. Inhibitor of phospholipase-C-dependent phosphoinositide hydrolysis,
      neomycin sulfate, reduced the Peth as well as the DAG response to L-T4.
      CONCLUSIONS: The present data have indicated the DAG signaling in thyroid hormone
      stimulated liver cells. L-thyroxine activates a dual phospholipase pathway in a
      sequential and synchronized manner: phospholipase C initiates the DAG formation,
      and PKC mediates the integration of phospholipase D into the signaling response
      during the sustained phase of agonist stimulation.

PMID- 11313001
TI  - Assessment of Equine Autoimmune Thrombocytopenia (EAT) by flow cytometry.
AB  - RATIONALE: Thrombocytopenia is a platelet associated process that occurs in human
      and animals as result of i) decreased production; ii) increased utilization; iii)
      increased destruction coupled to the presence of antibodies, within a process
      know as immune-mediated thrombocytopenia (IMT); or iv) platelet sequestration.
      Thus, the differentiation of the origin of IMT and the development of reliable
      diagnostic approaches and methodologies are important in the clarification of IMT
      pathogenesis. Therefore, there is a growing need in the field for easy to perform
      assays for assessing platelet morphological characteristics paired with detection
      of platelet-bound IgG. OBJECTIVES: This study is aimed to develop and
      characterize a single color flow cytometric assay for detection of platelet-bound
      IgG in horses, in combination with flow cytometric assessment of platelet
      morphological characteristics. FINDINGS: The FSC and SSC evaluation of the
      platelets obtained from the thrombocytopenic animals shows several distinctive
      features in comparison to the flow cytometric profile of platelets from healthy
      animals. The thrombocytopenic animals displayed i) increased number of platelets
      with high FSC and high SSC, ii) a significant number of those gigantic platelets
      had strong fluorescent signal (IgG bound), iii) very small platelets or platelet
      derived microparticles were found significantly enhanced in one of the
      thrombocytopenic horses, iv) significant numbers of these
      microplatelet/microparticles/platelet-fragments still carry very high
      fluorescence. CONCLUSIONS: This study describes the development and
      characterization of an easy to perform, inexpensive, and noninvasive single color
      flow cytometric assay for detection of platelet-bound IgG, in combination with
      flow cytometric assessment of platelet morphological characteristics in horses.

PMID- 11313002
TI  - Historical background.
AB  - The persisting ancient view of cancer as a contagious disease ended with 19th
      century scientific investigations which seemed to show it was not. The resulting
      dogma against an infectious cause for cancer produced great prejudice in the
      scientific community against the first report of an oncogenic virus by Rous early
      in the 20th century and, even in the 1950s, against Gross's finding of a murine
      leukaemia virus and a murine virus causing solid tumours. The Lucke frog renal
      carcinoma virus was the first cancer-associated herpesvirus. Intriguingly, an
      environmental factor, ambient temperature, determines virus genome expression in
      the poikilothermic frog cells. Although an alpha-herpesvirus, Marek's disease
      virus of chickens shares some aspects of biological behaviour with Epstein-Barr
      virus (EBV) of man. Very significantly, its lymphomas are the first naturally
      occurring malignancy to be controlled by an antiviral vaccine, with implications
      for human virus-associated cancers. The circumstances and climate of opinion in
      which successive gamma-herpesviruses were discovered are described. The
      identification of EBV involved two unconventionalities: its finding in cultured
      Burkitt's lymphoma cells when no human lymphoid cell had ever been maintained in
      vitro, and its recognition in the absence of biological activity by the then new
      technique of electron microscopy. These factors engendered hostility to its
      acceptance as a new human tumour-associated virus. The EBV-like agents of Old
      World apes and monkeys and the T-lymphotropic gamma-herpesviruses of New World
      monkeys were found at about the same time, not long after the discovery of EBV.
      For many years these were thought to be the only gamma-herpesviruses of non-human
      primates; however, very recently B-lymphotropic EBV-like agents have been
      identified in New World species as well. Mouse herpesvirus 68 came to light by
      chance during a search for arboviruses and has become important as a laboratory
      model because of its close genetic relatedness to EBV and its comparable
      biological behaviour. The discovery of Kaposi's sarcoma-associated herpesvirus
      six years ago was made using unconventional new methods, but, unlike with EBV 30
      years before, this did not hinder its acceptance. This contrast is discussed in
      the context of the great progress in human tumour virology which has been made in
      recent years.

PMID- 11313003
TI  - Molecular evolution of the gamma-Herpesvirinae.
AB  - Genomic sequences available for members of the gamma-Herpesvirinae allow analysis
      of many aspects of the group's evolution. This paper examines four topics: (i)
      the phylogeny of the group; (ii) the histories of gamma-herpesvirus-specific
      genes; (iii) genomic variation of human herpesvirus 8 (HHV-8); and (iv) the
      relationship between Epstein-Barr virus types 1 and 2 (EBV-1 and EBV-2). A
      phylogenetic tree based on eight conserved genes has been constructed for eight
      gamma-herpesviruses and extended to 14 species with smaller gene sets. This gave
      a generally robust assignment of evolutionary relationships, with the exception
      of murine herpesvirus 4 (MHV-4), which could not be placed unambiguously on the
      tree and which has evidently experienced an unusually high rate of genomic
      change. The gamma-herpesviruses possess a variable complement of genes with
      cellular homologues. In the clearest cases these virus genes were shown to have
      originated from host genome lineages in the distant past. HHV-8 possesses at its
      left genomic terminus a highly diverse gene (K1) and at its right terminus a gene
      (K15) having two diverged alleles. It was proposed that the high diversity of K1
      results from a positive selection on K1 and a hitchhiking effect that reduces
      diversity elsewhere in the genome. EBV-1 and EBV-2 differ in their alleles of the
      EBNA-2, EBNA-3A, EBNA-3B and EBNA-3C genes. It was suggested that EBV-1 and EBV-2
      may recombine in mixed infections so that their sequences outside these genes
      remain homogeneous. Models for genesis of the types, by recombination between
      diverged parents or by local divergence from a single lineage, both present
      difficulties.

PMID- 11313005
TI  - Biology and disease associations of Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) is a human herpesvirus which infects almost all of the
      world's population subclinically during childhood and thereafter remains in the
      body for life. The virus colonizes antibody-producing (B) cells, which, as
      relatively long-lived resting cells, are an ideal site for long-term residence.
      Here EBV evades recognition and destruction by cytotoxic T cells. EBV is passed
      to naive hosts in saliva, but how the virus gains access to this route of
      transmission is not entirely clear. EBV carries a set of latent genes that, when
      expressed in resting B cells, induce cell proliferation and thereby increase the
      chances of successful virus colonization of the B-cell system during primary
      infection and the establishment of persistence. However, if this cell
      proliferation is not controlled, or if it is accompanied by additional genetic
      events within the infected cell, it can lead to malignancy. Thus EBV acts as a
      step in the evolution of an ever-increasing list of malignancies which are
      broadly of lymphoid or epithelial cell origin. In some of these, such as B
      lymphoproliferative disease in the immunocompromised host, the role of the virus
      is central and well defined; in others, such as Burkitt's lymphoma, essential
      cofactors have been identified which act in concert with EBV in the evolution of
      the malignant clone. However, in several diseases in which the presence of EBV
      has more recently been discovered, the role of the virus is unclear. This review
      describes recent views on the EBV life cycle and its interlinks with normal B
      cell biology, and discusses how this interrelationship may be upset and result in
      EBV-associated disease.

PMID- 11313006
TI  - The immunology of Epstein-Barr virus infection.
AB  - Epstein-Barr virus is a classic example of a persistent human virus that has
      caught the imagination of immunologists, virologists and oncologists because of
      the juxtaposition of a number of important properties. First, the ability of the
      virus to immortalize B lymphocytes in vitro has provided an antigen presenting
      cell in which all the latent antigens of the virus are displayed and are
      available for systematic study. Second, the virus presents an ideal system for
      studying the immune parameters that maintain latency and the consequences of
      disturbing this cell-virus relationship. Third, this wealth of immunological
      background has provided a platform for elucidating the role of the immune system
      in protection from viral-associated malignancies of B cell and epithelial cell
      origin. Finally, attention is now being directed towards the development of
      vaccine formulations which might have broad application in the control of human
      malignancies.

PMID- 11313007
TI  - Simian homologues of Epstein-Barr virus.
AB  - Gamma-herpesviruses closely related to the Epstein-Barr virus (EBV) are known to
      naturally infect Old World non-human primates and are classified in the same
      lymphocryptovirus (LCV) genera. LCV infecting humans and Old World primates share
      similar biology, and recent studies have demonstrated that these viruses share a
      similar repertoire of viral genes. Surprisingly, the latent infection genes
      associated with cell growth transformation demonstrate the most striking sequence
      divergence, but the functional mechanisms for these genes are generally well
      conserved. The recent discovery of LCVs naturally infecting New World primates
      has rewritten the old paradigm of LCV host range restriction to humans and Old
      World non-human primates, so that these viruses are more widespread than
      previously believed. However, the New World LCV genome has significant and
      interesting differences from EBV and other Old World LCVs despite similar
      biological properties. Thus, the simian homologues of EBV can provide an
      important animal model for studying LCV pathogenesis, and the similarities and
      differences that have evolved among these related viruses can provide a unique
      perspective towards a better understanding of EBV.

PMID- 11313004
TI  - Molecular virology of Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) interacts with its host in three distinct ways in a
      highly regulated fashion: (i) EBV infects human B lymphocytes and induces
      proliferation of the infected cells, (ii) it enters into a latent phase in vivo
      that follows the proliferative phase, and (iii) it can be reactivated giving rise
      to the production of infectious progeny for reinfection of cells of the same type
      or transmission of the virus to another individual. In healthy people, these
      processes take place simultaneously in different anatomical and functional
      compartments and are linked to each other in a highly dynamic steady-state
      equilibrium. The development of a genetic system has paved the way for the
      dissection of those processes at a molecular level that can be studied in vitro,
      i.e. B-cell immortalization and the lytic cycle leading to production of
      infectious progeny. Polymerase chain reaction analyses coupled to fluorescent
      activated cell sorting has on the other hand allowed a descriptive analysis of
      the virus-host interaction in peripheral blood cells as well as in tonsillar B
      cells in vivo. This paper is aimed at compiling our present knowledge on the
      process of B-cell immortalization in vitro as well as in vivo latency, and
      attempts to integrate this knowledge into the framework of the viral life cycle
      in vivo.

PMID- 11313008
TI  - Molecular virology of Kaposi's sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), the most recently discovered
      human tumour virus, is the causative agent of Kaposi's sarcoma, primary effusion
      lymphoma and some forms of Castleman's disease. KSHV is a rhadinovirus, and like
      other rhadinoviruses, it has an extensive array of regulatory genes obtained from
      the host cell genome. These pirated KSHV proteins include homologues to cellular
      CD21, three different beta-chemokines, IL-6, BCL-2, several different interferon
      regulatory factor homologues, Fas-ligand ICE inhibitory protein (FLIP), cyclin D
      and a G-protein-coupled receptor, as well as DNA synthetic enzymes including
      thymidylate synthase, dihydrofolate reductase, DNA polymerase, thymidine kinase
      and ribonucleotide reductases. Despite marked differences between KSHV and
      Epstein-Barr virus, both viruses target many of the same cellular pathways, but
      use different strategies to achieve the same effects. KSHV proteins have been
      identified which inhibit cell-cycle regulation checkpoints, apoptosis control
      mechanisms and the immune response regulatory machinery. Inhibition of these
      cellular regulatory networks app ears to be a defensive means of allowing the
      virus to escape from innate antiviral immune responses. However, due to the
      overlapping nature of innate immune and tumour-suppressor pathways, inhibition of
      these regulatory networks can lead to unregulated cell proliferation and may
      contribute to virus-induced tumorigenesis.

PMID- 11313009
TI  - Epidemiology and pathogenesis of Kaposi's sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma (KS) occurs in Europe and the Mediterranean countries (classic
      KS) and Africa (endemic KS), immunosuppressed patients (iatrogenic or post
      transplant KS) and those with acquired immune deficiency syndrome (AIDS),
      especially among those who acquired human immunodeficiency virus sexually (AIDS
      KS). KS-associated herpesvirus (KSHV or HHV-8) is unusual among herpesviruses in
      having a restricted geographical distribution. Like KS, which it induces in
      immunosuppressed or elderly people, the virus is prevalent in Africa, in
      Mediterranean countries, among Jews and Arabs and certain Amerindians. Distinct
      KSHV genotypes occur in different parts of the world, but have not been
      identified as having a differential pathogenesis. KSHV is aetiologically linked
      to three distinct neoplasms: (i) KS, (ii) primary effusion lymphoma, and (iii)
      plasmablastic multicentric Castleman's disease. The histogenesis, clonality and
      pathology of the tumours are described, together with the epidemiology and
      possible modes of transmission of the virus.

PMID- 11313010
TI  - Simian homologues of human herpesvirus 8.
AB  - Gamma-herpesviruses can be found in most primates including Old World an New
      World monkeys. The gamma-herpesvirinae are grouped into two classes:
      lymphocryptoviruses (gamma1) and rhadinoviruses (gamma2). The lymphocryptoviruses
      include Epstein-Barr virus, lymphocryptovirus of rhesus monkeys, and Herpesvirus
      papio of baboons. Rhadinoviruses that infect New World monkeys include
      Herpesvirus saimiri, whose natural host is the squirrel monkey, and Herpesvirus
      ateles, which infects spider monkeys. Rhadinoviruses that infect hominoids and
      Old World monkeys include Kaposi's sarcoma-associated herpesvirus, also known as
      HHV-8, and rhesus monkey rhadinovirus.

PMID- 11313011
TI  - Herpesvirus saimiri.
AB  - Herpesvirus saimiri (saimiriine herpesvirus 2) is the classical prototype of the
      gamma(2)-herpesviruses or rhadinoviruses, which also contains a human member, the
      Kaposi's sarcoma-associated herpesvirus. The T-lymphotropic Herpesvirus saimiri
      establishes specific replicative and persistent conditions in different primate
      host species. Virtually all squirrel monkeys (Saimiri sciureus) are persistently
      infected with this virus. In its natural host, the virus does not cause disease,
      whereas it induces fatal acute T-cell lymphoma in other monkey species after
      experimental infection. The virus can be isolated by cocultivation of permissive
      epithelial cells with peripheral blood cells from naturally infected squirrel
      monkeys and from susceptible New World monkeys during the virus-induced disease.
      Tumour-derived and in vitro-transformed T-cell lines from New World monkeys
      release virus particles. Herpesvirus ateles is a closely related virus of spider
      monkeys (Ateles spp.) and has similar pathogenic properties to Herpesvirus
      saimiri in other New World primate species. Similar to other rhadinoviruses, the
      genome of Herpesvirus saimiri harbours a series of virus genes with pronounced
      homology to cellular counterparts including a D-type cyclin, a G-protein-coupled
      receptor, an interleukin-17, a superantigen homologue, and several inhibitors of
      the complement cascade and of different apoptosis pathways. Preserved function
      has been demonstrated for most of the homologues of cellular proteins. These
      viral functions are mostly dispensable for the transforming and pathogenic
      capability of the virus. However, they are considered relevant for the
      apathogenic persistence of Herpesvirus saimiri in its natural host. A terminal
      region of the non-repetitive coding part of the virus genome is essential for
      pathogenicity and T-cell transformation. Based on the pathogenic phenotypes and
      the different alleles of this variable region, the virus strains have been
      assigned to three subgroups, termed A, B and C. In the highly oncogenic subgroup
      C strains, the two virus genes stpC and tip are transcribed from one bicistronic
      mRNA and are essential for transformation and leukaemia induction. stpC fulfils
      the typical criteria of an oncogene; its product interacts with Ras and tumour
      necrosis factor-associated factors and induces mitogen-activated protein kinase
      and nuclear factor kappa B activation. Tip interacts with the RNA transport
      factor Tap, with signal transduction and activation of transcription factors, and
      with the T-cellular tyrosine kinase Lck, which is activated by this interaction
      and phosphorylates Tip as a substrate. It is of particular interest that certain
      subgroup C virus strains such as C488 are capable of transforming human T
      lymphocytes to stable growth in culture. The transformed human T cells harbour
      multiple copies of the viral genome in the form of stable, non-integrated
      episomes. The cells express only a few virus genes and do not produce virus
      particles. The transformed cells maintain the antigen specificity and many other
      essential functions of their parental T-cell clones. Based on the preserved
      functional phenotype of the transformed T cells, Herpesvirus saimiri provides
      useful tools for T-cell immunology, for gene transfer and possibly also for
      experimental adoptive immunotherapy.

PMID- 11313012
TI  - Natural history of murine gamma-herpesvirus infection.
AB  - Murine gamma-herpesvirus 68 (MHV-68) is a natural pathogen of small rodents and
      insectivores (mice, voles and shrews). The primary infection is characterized by
      virus replication in lung epithelial cells and the establishment of a latent
      infection in B lymphocytes. The virus is also observed to persist in lung
      epithelial cells, dendritic cells and macrophages. Splenomegaly is observed two
      weeks after infection, in which there is a CD4+ T-cell-mediated expansion of B
      and T cells in the spleen. At three weeks post-infection an infectious
      mononucleosis-like syndrome is observed involving a major expansion of
      Vbeta4+CD8+ T cells. Later in the course of persistent infection, ca. 10% of mice
      develop lymphoproliferative disease characterized as lymphomas of B-cell origin.
      The genome from MHV-68 strain g2.4 has been sequenced and contains ca. 73 genes,
      the majority of which are collinear and homologous to other gamma-herpesviruses.
      The genome includes cellular homologues for a complement-regulatory protein, Bcl
      2, cyclin D and interleukin-8 receptor and a set of novel genes M1 to M4. The
      function of these genes in the context of latent infections, evasion of immune
      responses and virus-mediated pathologies is discussed. Both innate and adaptive
      immune responses play an active role in limiting virus infection. The absence of
      type I interferon (IFN) results in a lethal MHV-68 infection, emphasizing the
      central role of these cytokines at the initial stages of infection. In contrast,
      type II IFN is not essential for the recovery from infection in the lung, but a
      failure of type II IFN receptor signalling results in the atrophy of lymphoid
      tissue associated with virus persistence. Splenic atrophy appears to be the
      result of immunopathology, since in the absence of CD8+ T cells no pathology
      occurs. CD8+ T cells play a major role in recovery from the primary infection,
      and also in regulating latently infected cells expressing the M2 gene product.
      CD4+ T cells have a key role in surveillance against virus recurrences in the
      lung, in part mediated through 'help' in the genesis of neutralizing antibodies.
      In the absence of CD4+ T cells, virus-specific CD8+ T cells are able to control
      the primary infection in the respiratory tract, yet surprisingly the memory CD8+
      T cells generated are unable to inhibit virus recurrences in the lung. This could
      be explained in part by the observations that this virus can downregulate major
      histocompatibility complex class I expression and also restrict inflammatory cell
      responses by producing a chemokine-binding protein (M3 gene product). MHV-68
      provides an excellent model to explore methods for controlling gamma-herpesvirus
      infection through vaccination and chemotherapy. Vaccination with gp150 (a
      homologue of gp350 of Epstein-Barr virus) results in a reduction in splenomegaly
      and virus latency but does not block replication in the lung, nor the
      establishment of a latent infection. Even when lung virus infection is greatly
      reduced following the action of CD8+ T cells, induced via a prime-boost
      vaccination strategy, a latent infection is established. Potent antiviral
      compounds such as the nucleoside analogue 2'deoxy-5-ethyl-beta-4'-thiouridine,
      which disrupts virus replication in vivo, cannot inhibit the establishment of a
      latent infection. Clearly, devising strategies to interrupt the establishment of
      latent virus infections may well prove impossible with existing methods.

PMID- 11313014
TI  - Concluding overview: looking back, looking forward.
AB  - The gamma-herpesviruses are a group of related agents which share the same broad
      strategy for infection of and persistence within the lymphoid tissues of their
      hosts. Yet in evolutionary terms these agents are sufficiently diverse to display
      multiple different molecular mechanisms whereby that strategy can be achieved.
      Attempts are made to relate the different in vitro growth transforming capacities
      of the gamma1-herpesviruses, the T-lymphotropic gamma2-herpesviruses and the B
      lymphotropic gamma2-herpesviruses to what is known about the biology of these
      virus infections in their natural or in experimental hosts. The review then
      summarizes the evidence linking gamma-herpesviruses with oncogenesis and proposes
      that the diverse spectrum of Epstein-Barr virus and human herpesvirus 8
      associated human tumours falls into three pathogenetically distinct categories.
      Many questions remain unanswered in the areas of gamma-herpesvirus biology and
      disease pathogenesis: resolving these questions will require a broadening of our
      experimental approaches and a willingness to relinquish 'single-model' panaceas.

PMID- 11313013
TI  - Dissecting the host response to a gamma-herpesvirus.
AB  - The murine gamma-herpesvirus 68 (MHV-68) provides a unique experimental model for
      dissecting immunity to large DNA viruses that persist in B lymphocytes. The
      analysis is greatly facilitated by the availability of genetically disrupted (-/
      ) mice that lack key host-response elements, and by the fact that MHV-68 is a
      lytic virus that can readily be manipulated for mutational analysis. The mutant
      virus strategy is being used, for example, to characterize the part played in
      vivo by an MHV-68-encoded chemokine-binding protein that may ultimately find an
      application in human therapeutics. Experiments with various -/- mice and
      monoclonal antibody depletion protocols have shown very clearly that type I
      interferons (IFNs) are essential for the early control of MHV-68 replication,
      while CD4+ T cells producing IFN-gamma function to limit the consequences of
      viral persistence. Virus-specific CD8+ effectors acting in the absence of the
      CD4+ subset seem initially to control the lytic phase in the lung following
      respiratory challenge, but are then unable to prevent the reactivation of
      replicative infection in epithelia and the eventual death of CD4+ T-cell
      deficient mice. This could reflect the fact that the interaction between the CD8+
      T cells and the virus-infected targets is partially compromised by the MHV-68 K3
      protein, which inhibits antigen presentation by MHC class I glycoproteins.
      Immunization strategies focusing on the CD8+ T-cell response to epitopes
      expressed during the lytic phase of MHV-68 infection can limit virus replication,
      but are unable to prevent the establishment of latency. Other experiments with
      mutant viruses also suggest that there is a disconnection between lytic MHV-68
      infection and latency. The massive nonspecific immunoglobulin response and the
      dramatic expansion of Vbeta4+ CD8+ T cells, which is apparently MHC independent,
      could represent some sort of 'smoke screen' used by MHV-68 to subvert immunity.
      Although MHV-68 is neither Epstein-Barr virus nor human herpesvirus-8, the
      results generated from this system suggest possibilities that may usefully be
      addressed with these human pathogens. Perhaps the main lesson learned to date is
      that all the components of immunity are likely to be important for the control of
      these complex viruses.

PMID- 11313015
TI  - Sequence, organization, chromosomal localization, and alternative splicing of the
      human serine protease inhibitor gene hurpin (PI13) which is upregulated in
      psoriasis.
AB  - Hurpin (protease inhibitor 13; PI13) is the most recently identified member of
      the ovalbumin family of serine protease inhibitors (serpins). It is expressed in
      human epidermal keratinocytes and is downregulated by exposure to ultraviolet
      irradiation. A role for hurpin in the proliferation or differentiation of
      keratinocytes has been proposed because of its strong expression in proliferating
      cells and its deregulated expression in the lesional epidermis of psoriatic
      patients. Here, we report the cloning, chromosomal localization, and complete
      sequence of the human hurpin gene. By PCR-based screening of the GeneBridge 4
      radiation hybrid panel, we mapped the gene to chromosome 18q21.3, close to a
      known cluster of ov-serpin genes. Using the full-length cDNA for hurpin, we
      identified two clones from an arrayed genomic P1 placental library that contain
      the entire hurpin gene. Sequencing revealed that the gene covers 12.253 kb and is
      comprised of eight exons and seven introns. The exon--intron boundaries are
      identical in position and phasing to those in other members of the 18q serpin
      gene cluster, and analysis of hurpin variants indicated that modified functional
      inhibitors, differing only in the CD interhelical loop, can be generated by
      differential splicing of exon 3. These data show that hurpin is a typical member
      of the 18q ovalbumin-serpins most closely related to the serpins squamous-cell
      carcinoma antigens 1 and 2.

PMID- 11313016
TI  - The Sp1 transcription factor regulates cell type-specific transcription of MUC1.
AB  - Because the MUC1 mucin is highly expressed in breast and other carcinomas,
      interest is focused on the MUC1 promoter, particularly in the context of the
      delivery of genes to carcinomas. Earlier in vitro studies showed that the region
      between -152 and -66 of the MUC1 promoter is required for transcriptional
      activity in MUC1-expressing cells. Experiments reported here showed that
      sequences -119/-62 within this region are able to modulate transcription of the
      heterologous constitutively active herpes simplex virus thymidine kinase promoter
      in a pattern consistent with MUC1 expression. Band-shift experiments showed that
      although several factors (including Sp1 and Sp3) bind to these sequences, the
      element important in directing this MUC1 pattern of expression was an Sp1 GC box
      at -97. The data also show that the positioning or phase of the GC box was
      crucial for directing expression. The importance of the Sp1 transcription factor
      was confirmed by demonstrating that overexpression of Sp1 in MUC1-nonexpressing
      cells increased, not only the expression of a reporter gene driven by the 1.4-kb
      MUC1 promoter, but also the expression of MUC1 from the endogenous gene.
      Together, these data define an important role for Sp1 in the cell type-specific
      transcription of MUC1.

PMID- 11313018
TI  - Molecular characterization of murine pancreatic phospholipase A(2).
AB  - The pancreatic secretory phospholipase A(2) (sPLA(2)IB) is considered to be a
      digestive enzyme, although it has several important receptor-mediated functions.
      In this study, using the newly isolated murine sPLA(2)IB cDNA clone as a probe,
      we demonstrate that in addition to the pancreas, the sPLA(2)IB mRNA was expressed
      in extrapancreatic organs such as the liver, spleen, duodenum, colon, and lungs.
      We also demonstrate that sPLA(2)IB mRNA expression was detectable from the 17(th)
      day of gestation in the developing mouse fetus, coinciding with the time of
      completion of differentiation of the pancreas. Furthermore, the mRNA expression
      pattern of sPLA(2)IB was distinct from those of sPLA(2)IIA and cPLA(2) in various
      tissues examined. The murine sPLA(2)IB gene structure is well conserved,
      consistent with findings in other mammalian species, and this gene mapped to the
      region of mouse chromosome 5F1-G1.1. Taken together, our results suggest that
      sPLA(2)IB plays important roles both in the pancreas and in extrapancreatic
      tissues and that in the mouse, its expression is developmentally regulated.

PMID- 11313017
TI  - Genomic analysis and localization of murine Deltex, a modulator of notch
      activity, to mouse chromosome 5 and its human homolog to chromosome 12.
AB  - Deltex is a component of the Notch signaling network, which mediates cellular
      differentiation, proliferation, and apoptosis during development. Murine Deltex
      was initially isolated as a cDNA transcript that displayed increased expression
      in T-cell tumors induced by gamma irradiation. The in vivo function of Deltex is
      unknown; however, the emerging role of Notch signaling in T-cell development and
      lymphomagenesis indirectly supports a role for Deltex in these processes. To
      investigate the regulation of Deltex expression in both normal and transformed
      tissue, we have begun analyzing the Deltex genomic locus. Here, we report the
      exon-intron organization of Deltex and map the locus to the middistal region of
      mouse chromosome 5, tightly linked to the Adam1a, Lnk, Tbx5, and Nos1 loci. The
      human homolog of Deltex has been localized to chromosome 12.

PMID- 11313019
TI  - Alternative promoter usage and splicing of ZNF74 multifinger gene produce protein
      isoforms with a different repressor activity and nuclear partitioning.
AB  - We have previously shown that ZNF74, a candidate gene for DiGeorge syndrome,
      encodes a developmentally expressed zinc finger gene of the Kruppel-associated
      box (KRAB) multifinger subfamily. Using RACE, RT-PCR, and primer extension on
      human fetal brain and heart mRNAs, we here demonstrate the existence of six mRNA
      variants resulting from alternative promoter usage and splicing. These
      transcripts encode four protein isoforms differing at their N terminus by the
      composition of their KRAB motif. One isoform, ZNF74-I, which corresponds to the
      originally cloned cDNA, was found to be encoded by two additional mRNA variants.
      This isoform, which contains a KRAB motif lacking the N terminus of the KRAB A
      box, was devoid of transcriptional activity. In contrast, ZNF74-II, a newly
      identified form of the protein that is encoded by a single transcript and
      contains an intact KRAB domain with full A and B boxes, showed strong repressor
      activity. Deconvolution immunofluorescence microscopy using transfected human
      neuroblastoma cells and nonimmortalized HS68 fibroblasts revealed a distinct
      subcellular distribution for ZNF74-I and ZNF74-II. In contrast to ZNF74-I, which
      largely colocalizes with SC-35 in nuclear speckles enriched in splicing factors,
      the transcriptionally active ZNF74-II had a more diffuse nuclear distribution
      that is more characteristic of transcriptional regulators. Taken with the
      previously described RNA-binding activity of ZNF74-I and direct interaction with
      a hyperphosphorylated form of the RNA polymerase II participating in pre-mRNA
      processing, our results suggest that the two ZNF74 isoforms exert different or
      complementary roles in RNA maturation and in transcriptional regulation.

PMID- 11313020
TI  - Effects of plasmid DNA injection on cyclophosphamide-accelerated diabetes in NOD
      mice.
AB  - Type 1 diabetes results in most cases from the destruction of insulin-secreting
      beta cells by the immune system. Several immunization methods based on
      administration of autoantigenic polypeptides such as insulin and glutamic acid
      decarboxylase (GAD) have been used to prevent autoimmune diabetes in the non
      obese diabetic (NOD) mouse. In the work presented here, a gene-based approach was
      taken for a similar purpose. A plasmid carrying different cDNAs was used to
      investigate the effects of injecting naked DNA on cyclophosphamide-accelerated
      diabetes in female NOD mice. Four-week-old animals received intramuscular
      injections of plasmid DNA encoding either intracellular GAD, a secreted form of
      GAD, or a secreted form of a soft coral luciferase. Monitoring of glycosuria and
      hyperglycemia indicated that injection of plasmid DNA encoding secreted GAD and
      secreted luciferase could prevent and delay diabetes, respectively. In contrast,
      injection of DNA encoding intracellular GAD did not suppress the disease
      significantly. Analysis of anti-GAD IgG(1) antibody titers in animal sera
      indicated that diabetes prevention after injection of GAD-encoding DNA was
      possibly associated with increased Th2-type activity. These results suggest that
      cellular localization of GAD is a factor to consider in the design of GAD-based
      genetic vaccines for the prevention of autoimmune diabetes.

PMID- 11313021
TI  - In vivo electroporation using an exponentially enhanced pulse: a new waveform.
AB  - In vivo electroporation is currently accomplished by one of two types of common
      waveforms: exponential decay or square-wave pulses. The purpose of this report is
      to present a new electroporation waveform, the exponentially enhanced pulse
      (EEP). Pulsing protocols including the EEP resulted in high levels of luciferase
      expression in muscle and skin, equal to or greater than expression resulting from
      low-voltage, millisecond square-wave pulses. This high level of expression
      requires fewer pulses when using an EEP protocol. Therefore, similar or greater
      plasmid DNA expression levels are obtained using fewer pulses with the EEP
      protocol than with current protocols. This is the first report of this new
      waveform and shows the success of using protocols employing the EEP to deliver
      plasmid DNA to various tissue types.

PMID- 11313022
TI  - Adhering to antiretroviral therapies.
AB  - In 1999, the AIDS program conducted a survey of more than 1,000 patients in Sao
      Paulo [Brazil]. It found that 69 percent achieved 80 percent adherence, which
      means they took their medicine properly 80 percent of the time. According to
      Margaret Chesney, a professor of medicine at the University of California at San
      Francisco who studies behavioral factors in AIDS treatment, this rate is not
      sufficient to control the virus - which can kill even people who take their
      medicine faithfully - but it is no different from adherence rates in the United
      States. A study in San Diego showed that 72 percent of patients took their
      medicine 80 percent of the time.

PMID- 11313023
TI  - Adherence assessment to highly active antiretroviral therapy.
AB  - Adherence to highly active antiretroviral therapy (HAART) is the outcome of a
      dynamic process of clinical and behavioral interactions. This article reviews
      factors influencing this process and provides suggestions to enhance adherence to
      HAART. Interventions to improve adherence to HAART should combine efficacy of
      treatments with a strong patient-provider alliance and cognitive behavioral
      interventions.

PMID- 11313024
TI  - HAART adherence in culturally diverse patients with HIV/AIDS: a study of male
      patients from a Veteran's Administration Hospital in northern California.
AB  - The objective of this study was to identify the factors that influence adherence
      to antiretroviral medication regimens in culturally diverse populations with
      human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS)
      related to age, ethnicity, and intravenous drug use. The critical incident
      technique was used to identify factors determining adherence. Through a series of
      brief, focused interviews, patients were asked to recall specific incidents that
      affected their adherence to HIV medications. Patients' responses were grouped
      into categories using Ethnograph software. Two nurse experts, with 94% agreement,
      determined the reliability of the category listings. A chi(2) analysis compared
      the proportion of patients reporting each factor across age, ethnicity, and
      intravenous drug use categories. The total sample of 52 participants included 46
      male outpatients with HIV/AIDS receiving care through a Veteran's Administration
      Hospital in northern California and 6 health care providers. The interviews
      yielded a total of 294 incidents. Six major categories were identified, and a
      taxonomy of critical factors determining highly active antiretroviral therapies
      (HAART) adherence was developed. The categories included reminders and cues
      (30%), planning (18%), response to HIV/AIDS (17%), HIV medication characteristics
      (14%), interactions with others (12%), and patient characteristics (10%). The two
      largest categories representing patient-related factors accounted for nearly half
      of the incidents. Patients most influenced by positive support from others
      included non-Caucasians, those under the age of 50 years, and those with fewer
      years of education. The taxonomy of adherence behaviors provides important
      information for developing culturally relevant patient adherence education
      programs and an essential foundation for developing future studies.

PMID- 11313025
TI  - Challenges of antiretroviral treatment in transient and drug-using populations:
      the SUN study.
AB  - This is an open-label, single-arm, phase 3b study (part of phase 3 development)
      to evaluate the efficacy and safety of Fortovase-soft gelatin formulation
      (saquinavir-SGC), combined with zidovudine (ZDV) and lamivudine (3TC), human
      immune deficiency virus type 1 in (HIV-1)-positive, antiretroviral-naive
      individuals. Forty-two HIV-1-positive adults with plasma HIV RNA >10,000 copies
      per milliliter (Roche Amplicor HIV Monitor assay) and CD4 cell count >100
      cells/mm(3) were treated with SQV-SGC, 1200 mg three times per day; ZDV, 300 mg;
      and 3TC, 150 mg each twice per day for 48 weeks. High proportions were drug users
      (26%), demonstrated psychiatric disorders (alcohol abuse [14%]/depression [14%]),
      or were inadequately housed (5%). At 48 weeks, 50% of patients achieved viral
      suppression <400 copies per milliliter with 43% <20 copies per milliliter using
      an intent-to-treat analysis (missing values counted as virological failures).
      Corresponding proportions for patients remaining on therapy at 48 weeks were 91%
      <400 copies per milliliter and 78% <20 copies per milliliter. Most adverse events
      were mild. Saquinavir-SGC combined with ZDV and 3TC, achieved potent and durable
      HIV RNA suppression and was well tolerated over 48 weeks in an antiretroviral
      naive population including high proportions of individuals considered difficult
      to treat, such as drug users, people with psychiatric problems and homeless
      individuals.

PMID- 11313027
TI  - Linking HIV-seropositive youth with health care: evaluation of an intervention.
AB  - The purpose of this study was to evaluate the use of a statewide human
      immunodeficiency virus (HIV) surveillance system to link infected adolescents
      with care. Eligible participants were HIV-seropositive youths who were reported
      to the Department of Health from 1985 to 1998 in a state with mandatory, name
      linked reporting of HIV and acquired immunodeficiency syndrome (AIDS) cases.
      Standard public health disease surveillance and intervention strategies were used
      to link participants with HIV/AIDS case management services. Enrollment in case
      management services was assessed before and after the intervention was
      implemented in 1993. The proportion of participants receiving case management
      services increased from 33% to 51% (p = 0.058) after the intervention was
      implemented. Although enrollment in case management did not vary significantly
      with participants' demographic and transmission characteristics, people of color
      were less likely than Caucasians to be located and interviewed. In conclusion,
      the system of name linked reporting of HIV/AIDS cases was used successfully to
      increase case management by 55% above baseline levels.

PMID- 11313026
TI  - Association between ancillary services and clinical and behavioral outcomes among
      HIV-infected women.
AB  - The purpose of this study was to evaluate the association between ancillary
      services, including case management, and clinical and behavioral outcomes for
      human immunodeficiency virus (HIV)-infected women. Data were obtained from
      databases systematically maintained by Family Advocacy, Care and Education
      Services (FACES) and the HIV Outpatient Program (HOP) in New Orleans. HIV
      infected women receiving primary care from HOP and ancillary services from FACES
      between January 1, 1997 and December 31, 1998 were eligible. Data were analyzed
      using generalized estimating equations (GEE) with STATA software. The majority of
      women included in the study were African American (86.7%), infected
      heterosexually (78.8%), and had absolute CD4 counts greater than 200 (58.6%).
      After adjusting for age, time, entry time into HOP, pregnancy, CD4 count,
      substance abuse status, and social and clinical stressors, receipt of more than
      four combined case manager contacts or ancillary services per month was
      significantly associated with being prescribed a protease inhibitor, improved
      adherence and retention in primary care, and enrolling on a research protocol.
      Receiving more than one transportation service per month was significantly
      associated with improved adherence, improved retention, one or more emergency
      room visits per month, and one or more hospitalizations per month. Receiving more
      than one contact with case managers per month was associated with improved
      retention in primary care. Findings suggest that receipt of case management and
      ancillary services is associated with improvements in multiple outcomes for HIV
      infected women. A client-centered approach to providing ancillary services
      appears to be effective in improving behavioral and utilization characteristics
      in this population of low-income, high-risk women.

PMID- 11313028
TI  - A multi-sectorial committee in directing HIV/AIDS-specific interventions in the
      occupational setting: an example from South Africa.
AB  - We present a descriptive analysis of a mechanism to coordinate and implement
      human immunodeficiency virus (HIV) prevention and care in the occupational
      setting. The mechanism we describe is a multidisciplinary committee composed of
      stakeholders in the occupational health environment including unions, management,
      medical researchers, and medical personnel. The site chosen for the analysis was
      a South African sugar mill in rural KwaZulu-Natal. The factory is situated in an
      area of high HIV seroprevalence and has a workforce of 400 employees. The
      committee was initiated to coordinate a combined prevention-care initiative. The
      issues that were important in the formation of the committee included
      confidentiality, trust, and the traditional roles of the stakeholder
      relationships. When these points were addressed through the focus on a common
      goal, the committee was able to function in its role as a coordinating body.
      Central to this success was the inclusion of all stakeholders in the process,
      including those with traditionally opposing interests and legitimacy conferred by
      the stakeholders. This committee was functionally effective and demonstrated the
      benefit of a freestanding committee dedicated to addressing HIV/acquired immune
      deficiency syndrome (AIDS) issues. We describe the implementation and feasibility
      of a multisectoral committee in directing HIV/AIDS initiatives in the
      occupational setting in rural South Africa.

PMID- 11313029
TI  - Use of complementary and alternative therapies in HIV-infected patients.
AB  - The use of complementary and alternative medicine (CAM) therapies is widespread
      in many chronic illnesses, including human immunodeficiency virus (HIV)
      infection. The objective of this study was to determine the impact of
      increasingly effective antiretroviral therapy on the use of CAM in an HIV
      positive patient population. A written survey was given to 191 HIV-positive
      outpatients. Participation was voluntary and anonymous. One hundred twenty-eight
      patients (67%) used CAM at some time to control HIV and 76 (40%) of the patients
      were currently using CAM. The major forms of CAM used were exercise (43%),
      lifestyle changes (38%), dietary supplements (37%), counseling (27%), herbal
      medications (26%), megavitamins (24%), and prayer therapy (24%). One hundred
      forty-one patients (74%) used a protease inhibitor medication, 28 (15%) used a
      protease inhibitor sparing regime, and 22 (11%) had no current or prior
      antiretroviral use. Eighty-two (43%) patients indicated that their doctor knew
      they used CAM and 56 patients (29%) received their information about CAM from a
      doctor or other health care professional. Of 128 patients who used CAM, 90 (70%)
      felt CAM improved their quality of life. Income of $15,000 or more per year and
      discontinuation of medications by patients for any reason in the past were the
      best predicators of CAM use for patients in general and also those on protease
      inhibitor therapy. CD(4) count, educational status, year of HIV diagnosis, and
      martial status were not effective predictors of CAM use. Use of CAM remains
      widespread among patients with HIV infection even with the availability of
      effective, yet noncurative antiretroviral therapy and does not correlate with
      type of antiretroviral therapy used or clinical status.

PMID- 11313030
TI  - HIV/AIDS case histories: indinavir crystalluria.

PMID- 11313031
TI  - Phase III trials for new PI.

PMID- 11313032
TI  - Methadone and cipro interaction.

PMID- 11313033
TI  - Evidence for a cerebellar role in reduced exploration and stereotyped behavior in
      autism.
AB  - BACKGROUND: Although limited environmental exploration in autism is an obvious
      behavioral feature and may be a manifestation of "restricted interests" as
      described in DSM-IV criteria, there have been no behavioral or neurobiological
      studies of this important aspect of the disorder. Given consistent reports of
      cerebellar abnormality in autism, combined with animal research showing a
      relationship between exploration and the cerebellum, this study aimed to test the
      possible link between cerebellar abnormality and exploration in autism. METHODS:
      The relationship between visuospatial exploration, stereotyped motor movements,
      and magnetic resonance imaging measures of the cerebellar vermis, whole brain
      volume, and frontal lobes in 14 autistic and 14 normal children was investigated.
      Children were exposed to a large room with several exploration containers and
      instructed to play. Exploration behavior was videotaped and scored for percentage
      of time engaged in exploration, number of containers explored, as well as
      stereotyped movements. RESULTS: Children with autism spent significantly less
      time in active exploration and explored fewer containers overall than normal
      children. Measures of decreased exploration were significantly correlated with
      the magnitude of cerebellar hypoplasia of vermal lobules VI-VII in the autistic
      children, but no relationship to vermis size was found with normal control
      children. Further, measures of rates of stereotyped behavior were significantly
      negatively correlated with area measures of cerebellar vermis lobules VI-VII and
      positively correlated with frontal lobe volume in the autism sample. CONCLUSIONS:
      Reduced environmental exploration and repetitive behavior may have particularly
      important developmental consequences for children with autism because it may lead
      them to miss learning opportunities that fall outside their scope of interest.
      Our findings represent the first documented link between the restricted range of
      interests and stereotyped behaviors pathognomonic of autism and particular
      neuroanatomic sites.

PMID- 11313034
TI  - Atypical patterns of cerebral motor activation in autism: a functional magnetic
      resonance study.
AB  - BACKGROUND: Early neurodevelopmental pathogenesis in autism potentially affects
      emerging functional maps, but little imaging evidence is available. METHODS: We
      studied eight male autistic and eight matched normal subjects, using functional
      magnetic resonance imaging during visually paced finger movement, compared to a
      control condition (visual stimulation in the absence of motor response). RESULTS:
      Groupwise analyses showed activation in contralateral perirolandic cortex, basal
      ganglia, and thalamus, bilateral supplementary motor area, and ipsilateral
      cerebellum for both groups. However, activations were less pronounced in the
      autism group. Direct group comparisons demonstrated greater activation in
      perirolandic and supplementary motor areas in the control group and greater
      activation (or reduced deactivation) in posterior and prefrontal cortices in the
      autism group. Intraindividual analyses further showed that strongest activations
      were consistently located along the contralateral central sulcus in control
      subjects but occurred in locations differing from individual to individual in the
      autism group. CONCLUSIONS: Our findings, though based on a rather small sample,
      suggest abnormal individual variability of functional maps and less distinct
      regional activation/deactivation patterns in autism. The observations may relate
      to known motor impairments in autism and are compatible with the general
      hypothesis of disturbances of functional differentiation in the autistic
      cerebrum.

PMID- 11313035
TI  - Regional cortical white matter reductions in velocardiofacial syndrome: a
      volumetric MRI analysis.
AB  - BACKGROUND: Velocardiofacial syndrome, caused by a microdeletion on chromosome
      22q.11, is associated with craniofacial anomalies, cardiac defects, learning
      disabilities, and psychiatric disorders. To understand how the 22q.11 deletion
      affects brain development, this study examined gray and white matter volumes in
      major lobar brain regions of children with velocardiofacial syndrome relative to
      control subjects. METHODS: Subjects were ten children with velocardiofacial
      syndrome and ten age- and gender-matched unaffected children. Coronal images were
      acquired with a 3-D spoiled gradient echo series and partitioned into 124, 1.5-mm
      contiguous slices. A stereotaxic grid was used to subdivide brain tissue into
      cerebral lobes, which were segmented into gray, white, and CSF compartments using
      an algorithm based on intensity values and tissue boundaries. Nonparametric
      statistics were used to compare lobar volumes of gray and white matter. RESULTS:
      Analyses indicated that children with velocardiofacial syndrome had significantly
      smaller volumes in nonfrontal, but not frontal, lobar brain regions. Volume
      reductions affected nonfrontal white matter to a greater extent than nonfrontal
      gray matter. CONCLUSIONS: The presence of white matter reductions may be related
      to disturbances in myelination or axonal integrity in velocardiofacial syndrome.
      Further work is required to delineate the nature and extent of white matter
      anomalies, and to link them to variation in the neurocognitive and
      neuropsychiatric phenotype of velocardiofacial syndrome.

PMID- 11313036
TI  - Are auditory hallucinations the consequence of abnormal cerebral lateralization?
      A morphometric MRI study of the sylvian fissure and planum temporale.
AB  - BACKGROUND: Auditory verbal hallucinations (AVHs) are a characteristic feature of
      schizophrenia. Patients with schizophrenia have been found to have reduced
      volumes of a variety of brain structures as well as a reduction in right-left
      asymmetries, using postmortem and magnetic resonance imaging (MRI) measures.
      There is also evidence that patients with AVHs differ in these structural
      asymmetries, relative to those patients who do not hallucinate. The aim of this
      study was to examine whether patients with and without a prominent history of
      AVHs differ, both from each other and in comparison with normal subjects, in the
      asymmetry of the sylvian fissure (SF) and planum temporale (PT). METHODS: We
      recruited 74 DSM-IV male patients with schizophrenia (on the basis of their AVH
      history) and 32 matched normal control subjects. Thirty patients had no history
      of AVHs and 44 had a strong definitive history of AVHs. The SF length and PT area
      and volume were measured on a three-dimensional MRI spoiled GRASS volume
      sequence. Absolute measures and laterality coefficients were calculated. RESULTS:
      : All groups had the normal leftward asymmetry in both the SF and PT. Planum
      temporale volume and surface area and SF length were all larger in the left
      hemisphere. There were no significant differences in any measures between the two
      patient groups or between schizophrenic patients and control subjects. Greater
      leftward asymmetry of the SF correlated with hallucinations and thought disorder
      within the prominent hallucinator group. An association was found between
      handedness and brain size, but this did not interact with diagnosis. CONCLUSIONS:
      The results of this study do not confirm reports, based on smaller samples, of
      reduced structural asymmetries of either the SF or PT in schizophrenia, nor do
      they indicate a specific relationship to a propensity to experience AVHs. A
      modest correlation between leftward asymmetry of the SF and some positive
      symptomatology was found.

PMID- 11313037
TI  - Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables
      in schizophrenia.
AB  - BACKGROUND: A growing body of literature suggests that schizophrenic patients
      often do not show the normal brain hemispheric asymmetry. We have found this for
      simple tones presented to the right ear in a previous study. In this study we
      extended this investigation to left ear stimulation and verbal stimuli. METHODS:
      With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked
      magnetic fields in response to tones (1000 Hz) and to the syllables ("ba")
      delivered to the left and right ears in separate runs were compared between
      schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS:
      In response to tones, all control subjects showed the expected asymmetry
      (contralateral predominance) of the auditory-evoked magnetic N100m (dipole
      moment). In the patient sample asymmetry was reversed following tones presented
      to the left ear in 47% and following tones to the right ear in 24%. In response
      to syllables, the asymmetry was similar between groups. In patients compared with
      control subjects the N100m was located more anterior without asymmetry between
      hemispheres. CONCLUSIONS: Results suggest that deviation from the normal
      functional lateralization in schizophrenia appears in a proportion of patients at
      a basic stage of auditory processing, but may be compensated for at higher levels
      such as the processing of syllables.

PMID- 11313038
TI  - Comparison of the effects of risperidone and haloperidol on regional cerebral
      blood flow in schizophrenia.
AB  - BACKGROUND: Atypical antipsychotics, such as risperidone, have been shown to be
      more effective for the treatment of the symptoms of schizophrenia and have a
      greater beneficial effect on neurocognition compared to the conventional
      antipsychotics. The present study used [(15)O]H(2)O positron emission tomography
      imaging of regional cerebral blood flow to examine and compare the effects of
      haloperidol and risperidone on brain function. METHODS: Thirty-two subjects with
      schizophrenia participated in the study. Each subject was scanned in a medication
      free state, and after being on a stable clinically assigned dose of either
      risperidone or haloperidol for 3 weeks. The off-medication scan was subtracted
      from the on-medication scan, using a within-subjects design. A randomization
      analysis was used to determine differences between the effects of haloperidol and
      risperidone on regional cerebral blood flow. RESULTS: Haloperidol was associated
      with a significantly greater increase in regional cerebral blood flow in the left
      putamen and posterior cingulate, and a significantly greater decrease in regional
      cerebral blood flow in frontal regions compared to risperidone. Risperidone was
      associated with a significantly greater decrease in regional cerebral blood flow
      in the cerebellum bilaterally compared to haloperidol. CONCLUSIONS: The results
      show that risperidone and haloperidol have significantly different effects on
      brain function, which may be related to their differences in efficacy and side
      effects. Further work is required to more precisely determine the mechanisms by
      which different antipsychotic medications exert their therapeutic effects on the
      clinical symptoms and cognition in schizophrenia. These findings emphasize the
      importance of controlling for both medication status and the individual
      antipsychotic in neuroimaging studies.

PMID- 11313039
TI  - The muscarinic agonist xanomeline increases monoamine release and immediate early
      gene expression in the rat prefrontal cortex.
AB  - BACKGROUND: The muscarinic agonist xanomeline has been shown to reduce
      antipsychotic-like behaviors in patients with Alzheimer's disease. Because
      atypical antipsychotic agents increase dopamine release in prefrontal cortex and
      induce immediate early gene expression in prefrontal cortex and nucleus
      accumbens, the effect of xanomeline was determined on these indices. METHODS: The
      effect of xanomeline on extracellular levels of monoamines in brain regions was
      determined using a microdialysis technique, and changes in expression of the
      immediate early genes c-fos and zif/268 in brain regions were evaluated using in
      situ hybridization histochemistry. RESULTS: Xanomeline increased extracellular
      levels of dopamine in prefrontal cortex and nucleus accumbens but not in
      striatum. Xanomeline increased expression of c-fos and zif/268 in prefrontal
      cortex and nucleus accumbens. There was no change in immediate early gene
      expression in striatum. CONCLUSIONS: Xanomeline increased extracellular levels of
      dopamine, which is similar to the effects of the atypical antipsychotics
      clozapine and olanzapine. The regional pattern of immediate early gene expression
      induced by xanomeline resembled that of atypical antipsychotic agents. Based on
      the antipsychotic-like activity of xanomeline in Alzheimer's patients and the
      similarity to atypical antipsychotic agents, we suggest that xanomeline may be a
      novel antipsychotic agent.

PMID- 11313040
TI  - Auditory P3a deficits in male subjects at high risk for alcoholism.
AB  - BACKGROUND: Substantial evidence indicates that alcoholism is biologically
      mediated by a genetic predisposition. As the decreased P300 (P3b) event-related
      brain potential component does not recover with prolonged abstinence, it is
      unlikely to be related to drinking history but is more likely to be genetically
      influenced. This is supported by findings that P3b amplitudes are reduced in
      subjects at high-risk compared to low-risk for alcoholism. Although there are few
      studies of P3a in HR subjects, lower P3a amplitudes have been reported with a
      novel nontarget stimulus paradigm, as well as with a difficult three-stimulus
      visual paradigm. Using a similar three-tone auditory paradigm in which the
      discriminability between the target and standard tone is difficult, the P3a
      component can also be reliably elicited with a rare nontarget perceptually
      distinct stimulus. This technique was employed in young adult subjects at low
      risk and high-risk for alcoholism. METHODS: A total of 17 low-risk and 24 high
      risk male subjects were employed as subjects in an auditory paradigm that yielded
      a large amplitude P3a with a centro-frontal maximum to the nontarget and a robust
      low amplitude prolonged P3b with a parietal maximum amplitude to the target
      stimulus. Current source density maps were derived to assess topographic
      differences between low-risk and high-risk subjects. RESULTS: The high-risk group
      manifested significantly lower P3a amplitudes than the low-risk group at the
      frontal electrodes to rare nontarget stimuli. High-risk subjects also
      demonstrated a more disorganized current source density map for P3a compared to
      low-risk subjects. CONCLUSIONS: The reduction of P3a in the high-risk group may
      be due to cortical dysfunction including the frontal and prefrontal cortex. The
      lower P3a amplitude coupled with more disorganized current source density maps
      suggest inefficient brain functioning in high-risk subjects.

PMID- 11313041
TI  - Combined effect of extracellular matrices and growth factors on bovine corneal
      endothelial cells in culture.
AB  - PURPOSE: First, to confirm that corneal endothelial cells in the confluent state
      have the capability to form cellular covering. Second, to establish a method to
      study the combined effect of extracellular matrices (ECMs) and growth factors on
      the biological response in corneal endothelial cells in culture. METHODS: Bovine
      corneal endothelial cells were cultured inside a cylinder set on a plastic dish.
      They formed a confluent cell nest on the dish coated with type I or type IV
      collagen, laminin, or fibronectin. After the removal of the cylinder, hepatocyte
      growth factor (HGF), epidermal growth factor, transforming growth factor-alpha or
      transforming growth factor-beta(1) was added to the cultures. Each confluent cell
      nest enlarged outward, and its increased area size was measured. Cellular
      response in the nest, including cellular proliferation, was analyzed. RESULTS:
      The size of the increased area of the culture on type IV collagen plus HGF was
      the largest of all the combinations of ECMs and growth factors. The responses of
      component cells in the increased area consisted of cellular hypertrophy,
      proliferation, migration and giant cell formation. The treatment with type IV
      collagen plus HGF clearly promoted all the above responses. CONCLUSIONS: The
      biological response of corneal endothelial cells was regulated by ECMs and growth
      factors.

PMID- 11313043
TI  - Ischemic hypertension of pigeon eye.
AB  - PURPOSE: To determine the etiology of open-angle glaucoma in human eyes, we
      tested the hypothesis that ischemia of the endothelial cells lining Schlemm's
      canal alters the intraocular pressure (IOP) by affecting the transport of fluids
      out of the eye. METHODS: Experiments were conducted on pigeons. After blocking
      the two major arteries to the aqueous sinus artery of one eye by laser
      photocoagulation, the episcleral arteries of both eyes were cauterized. The IOP
      was measured with a Mentor pneumatonometer before, immediately, and several days
      after blocking the major arteries. RESULTS: After the episcleral cauterization,
      the IOP of the laser-treated eye rose significantly and was maintained for at
      least 3 hours. By day 2, the IOP had recovered to the pre-cauterization level.
      The IOP of the control eye remained unchanged throughout the experiment.
      CONCLUSION: These results strongly support the hypothesis that ischemia of the
      endothelial cells lining Schlemm's canal plays a role in the control of the IOP.

PMID- 11313042
TI  - Intracameral and lenticular penetration of locally applied stable isotope-labeled
      vitamin E.
AB  - PURPOSE: To confirm the aqueous humor and lens dynamics of 1% deuterium-labeled
      alpha-tocopherol acetate (D(3)-VEA) solution. METHODS: The concentrations of D(3)
      VEA and D(3)-alpha-tocopherol (D(3)-VE), derived from D(3)-VEA, in the aqueous
      humor and lens were measured after continuous instillation of 1% D(3)-VEA into
      the cul-de-sac of rat eyes for 1 or 3 weeks. D(3)-VEA and D(3)-VE concentrations
      were determined by gas chromatography/mass selective detector. RESULTS: In the
      aqueous humor, the concentrations of D(3)-VEA and D(3)-VE were, respectively,
      93.1 and 9.4 ng/mL after 1 week, and, respectively, 498.9 and 21.5 ng/mL after 3
      weeks. In the lens, they were, respectively, 15.0 and 9.8 ng/g after 1 week, and
      6.1 and 4.8 ng/g after 3 weeks. CONCLUSION: The penetration levels of alpha
      tocopherol acetate by eyedrop application were confirmed in the aqueous humor and
      lens.

PMID- 11313044
TI  - Altered expression of genes in experimentally induced myopic chick eyes.
AB  - PURPOSE: To identify a casual pathway between the alteration in visual
      experience, due to form deprivation and hyperopic defocus, and the increase in
      eye growth, we searched for candidate genes having regulatory effects on eye
      growth under myopic conditions. METHODS: The expression of the brain-derived
      neurotrophic factor, neurotrophin-3, sonic hedgehog, nerve growth factor, Six-3
      and the Lh-2 group of genes in the transcriptional level after experimentally
      induced myopia (form-deprivation by goggles and by hyperopic defocus using
      negative spectacle lenses) were evaluated by semiquantitative reverse
      transcriptional polymerase chain reaction and Northern blot analysis. RESULTS:
      Results showed that only the sonic hedgehog gene was differentially expressed in
      the experimentally induced myopic retinal samples compared with controls.
      CONCLUSIONS: The sonic hedgehog gene may have regulatory functions in the
      signaling of the cascade of events that leads to axial elongation and vitreous
      enlargement of the eye under myopic conditions.

PMID- 11313045
TI  - Neovascularization in experimental retinal venous obstruction in rabbits.
AB  - PURPOSE: To investigate the later pathohistological changes in experimental
      retinal venous obstruction in rabbits. METHODS: Experimental retinal venous
      obstruction was produced in retinal blood vessels of rabbits by trans-adventitial
      dropping of thrombin. Fundus observation was performed 3 months and 1 year
      thereafter. Retinal histological examinations were performed by fluorescein
      microscopy, light microscopy, and transmission electron microscopy. RESULTS:
      Vessels with a rete mirabile and arteriovenous anastomosis were observed after 3
      months. On a flat gelatin-fluorescein preparation, regions with no perfusion,
      thought to be areas of vascular occlusion in the periphery, were observed
      extensively. Clear leakage of gelatin-added fluorescein was noted from vessels in
      the periphery, and minute neovascularization with a rete mirabile from these
      vessels was confirmed. Newly formed retinal vessels were also observed by
      transmission electron microscopy. The endothelial cells of these newly formed
      vessels had a large nucleus, a number of ribosomes, and thin basement membrane.
      Proliferative changes included glial cells that had penetrated into the basement
      membrane of ghost vessels. CONCLUSION: Our long-term observations confirmed that
      proliferative changes and neovascularization occurred in this model of retinal
      venous obstruction.

PMID- 11313046
TI  - Reproducibility of visual activation during checkerboard stimulation in
      functional magnetic resonance imaging at 4 Tesla.
AB  - PURPOSE: To investigate the reproducibility of visual activation by checkerboard
      stimulation, we used functional magnetic resonance imaging (fMRI) at 4 Tesla (T).
      METHODS: Four subjects were studied with fMRI at 4 T during checkerboard visual
      stimulation. The functional images were realigned and spatially normalized to the
      standard brain. For each subject, statistical parametric maps were made for each
      study, and the reproducibility was determined based on the number of supra
      threshold voxels (Z > 3.5, 4.5, and 5.5). RESULTS: The mean ratio for the number
      of supra-threshold (Z > 4.5) voxels was 0.75, and the mean ratio for the
      overlapping voxels was 0.61. Restricting the region of interest within the
      posterior half of the brain improved reproducibility values at the low threshold
      (Z > 3.5), but did not improve the values at the higher thresholds. CONCLUSIONS:
      Despite the fact that more than half of the supra-threshold voxels were found to
      be active for the repeated scans, visual activation with checkerboard stimulation
      seems to be less reproducible than that by flash stimulation.

PMID- 11313047
TI  - The refractive changes and long-term (3 years) results of radial keratotomy
      performed at high altitude.
AB  - PURPOSE: To evaluate the development of regression or progression following
      radial keratotomy (RK) performed at high altitude (1,720 meters) at long-term
      follow-up (3 years). METHODS: Thirty-nine eyes of 21 myopia patients (between 
      3.25 D and -11.00 D) whose ages were 19-32 years were included in the study. The
      RK procedures were performed in standard Russian style. RESULTS: The average
      spherical equivalent cycloplegic refractions were -5.49 D +/- 2.08 (SD)
      preoperatively, -1.64 +/- 1.59 D in the short-term (3.41 +/- 1.46 months) and 
      1.40 +/- 1.71 D in the long-term (30.72 +/- 4.36 months) follow-up period. There
      was no statistically significant difference between these values at the short-
      and long-term follow-up measurements (t = -1.57, P =.12). CONCLUSIONS: The
      refractive changes following RK performed at high altitude occur through a
      combination of both the direct effect of reduced barometric pressure and the
      edematous corneal expansion because of hypoxia. An ophthalmologist performing RK
      surgery at high altitude must consider the long-lasting therapeutic effects of
      high altitude surgery compared to surgery at sea level.

PMID- 11313048
TI  - Epidemic keratoconjunctivitis caused by a new genotype of adenovirus type 8 (Ad8)
      a chronological review of Ad8 in Southern Taiwan.
AB  - PURPOSE: To understand the pathogenic evolution of viral keratoconjunctivitis in
      Kaohsiung, Taiwan, a retrospective molecular and clinical analysis was conducted.
      METHODS: From January 1990 to December 1994, conjunctival swab samples from
      patients suspected of having viral conjunctivitis were collected for viral
      culture isolation, neutralization test (NT), and endonuclease cleavage analysis.
      Six restriction endonucleases, comprising HindIII, BamHI, SalI, SstI, SmaI, and
      PstI, were used for cleavage. Clinical examinations of patients were performed by
      two senior ophthalmologists. RESULTS: Twenty-one cases of a new genotype of
      adenovirus (Ad) type 8, designated as Ad8H, were discovered in the 27 detected
      adenovirus cases. The Ad8H has a distinct cleavage pattern, especially by HindIII
      and SalI. The Ad8H keratoconjunctivitis induced more subconjunctival hemorrhage
      (33.3%), keratitis (33.3%), and lymphadenopathy (85.7%) than other genotypes of
      Ad8 previously isolated in Kaohsiung, Taiwan. CONCLUSION: We have discovered a
      new genotype, Ad8H, which was prevalent as the main pathogen of the adenoviral
      keratoconjunctivitis in Kaohsiung, Taiwan from 1990 to 1994. Adenovirus type 8 is
      evolving into more genotypes with a trend towards more severe symptoms, including
      subconjunctival hemorrhage, keratitis, and lymphadenopathy.

PMID- 11313049
TI  - Relationship between motor alignment at postoperative day 1 and at year 1 after
      symmetric and asymmetric surgery in intermittent exotropia.
AB  - PURPOSE: To evaluate the relationship between the motor alignment at
      postoperative day 1 and at year 1 following bilateral lateral rectus recession
      (BLR, symmetric surgery) and unilateral lateral rectus recession-medial rectus
      resection (R&R, asymmetric surgery) for the treatment of intermittent exotropia,
      X(T). METHODS: Forty-six patients with basic or pseudo-divergence excess type of
      X(T) underwent BLR and 57 patients underwent R&R. The motor alignment at
      postoperative day 1 was classified as overcorrected by 11-20 prism diopters (PD),
      overcorrected by 1-10 PD, orthotropic, or undercorrected by 1-10 PD of exotropia.
      RESULTS: There was a statistically significant relationship between the alignment
      at postoperative day 1 and at year 1 following both R&R and BLR surgery (r =
      0.74, r = 0.51, respectively, P <.05). Patients overcorrected by 1-20 PD had a
      significantly higher success rate than those undercorrected by 1-10 PD on
      postoperative day 1 (P <.05). For R&R, a postoperative day 1 alignment of 1-10 PD
      resulted in the highest success rate of 73.7%. For BLR, a postoperative day 1
      alignment of 11-20 PD showed the highest success rate of 76.9%. There were no
      significant differences in the success, undercorrection and overcorrection rates
      between the two surgical procedures after a 1-year postoperative period.
      CONCLUSIONS: The alignment at postoperative day 1 can be a predictive factor of
      the surgical outcome in X(T). A postoperative day 1 overcorrection of 11-20 PD
      following BLR surgery and an overcorrection of 1-10 PD following R&R can lead to
      good results.

PMID- 11313050
TI  - Factors associated with increased aqueous flare in psoriasis.
AB  - PURPOSE: To evaluate the changes in aqueous flare in psoriasis patients and to
      identify the factors that influence the level of aqueous flare. METHODS: We
      examined the 68 eyes of 34 psoriasis patients and the 68 eyes of 34 healthy
      subjects with a laser flare-cell meter. Complete dermatologic and ophthalmic
      examinations were performed on the psoriasis patients. RESULTS: Flare was
      significantly higher in psoriasis patients than in normal controls (P <.000l).
      The factors that increased flare significantly were age and Psoriasis Area and
      Severity Index. Flare was not significantly associated with sex, psoriasis type,
      duration of disease, and cyclosporin therapy. A flare increase was significantly
      correlated with serum total protein and immunoglobulin (Ig) A, but not with
      albumin, IgG, and IgM. CONCLUSIONS: Psoriasis patients, even without ocular
      symptoms, had slight damage to the blood-aqueous barrier. Multiple linear
      regression analysis showed that flare had the strongest correlation with the
      severity of psoriasis.

PMID- 11313051
TI  - Treatment of Vogt-Koyanagi- Harada's disease during pregnancy.
AB  - BACKGROUND: Caution should be exercised in treating patients with autoimmune
      diseases during pregnancy. CASES: We successfully treated three cases of Vogt
      Koyanagi-Harada's disease (VKH disease) during pregnancy. OBSERVATIONS: In the
      second trimester (14-27 weeks) of 1 patient, inflammation was mild and could be
      treated by topical corticosteroid. There is the possibility that her immune
      response had been modified by pregnancy. Systemic corticosteroid in a high dose
      was administered to the two cases in the second and third trimesters of pregnancy
      (28-41 weeks). The severity of inflammation in these 2 patients was similar to
      that in nonpregnant women. Inflammation subsided immediately without recurrence
      in all cases. No abnormality was found during the deliveries or in the babies.
      CONCLUSIONS: Treatment for VKH disease during pregnancy should be chosen
      according to the severity of inflammation, the stage of pregnancy, and the
      maternal and fetal conditions.

PMID- 11313052
TI  - Prognosis of endogenous fungal endophthalmitis and utility of Ishibashi's
      classification.
AB  - PURPOSE: Evaluations of visual acuity outcomes of eyes with endogenous fungal
      endophthalmitis were made retrospectively, according to the classification
      proposed by Ishibashi. METHODS: We surveyed endogenous fungal endophthalmitis
      cases at the 4 Nihon University Hospitals and 20 affiliated hospitals. Sixty eyes
      of 34 patients were classified into five stages according to Ishibashi's system,
      and therapeutic methods and visual outcomes in each stage were then evaluated.
      RESULTS: Systemic antifungal drugs were efficacious in 82% of stage II and 69% of
      stage IIIa cases. Antifungal drugs were even efficacious in 42% of stage IIIb
      cases. Among the unresponsive cases, only half had been given the maximal dosage
      of antifungal drugs. Half of the eyes in which vitrectomy had been performed at
      stage IIIb achieved a postoperative visual acuity of 0.5 or better and none had a
      visual acuity of less than 0.03. CONCLUSION: Based on the above results, we
      concluded that systemic antifungal drugs should be administered at the maximal
      dosage to stage II and IIIa cases. If these eyes progress to stage IIIb despite
      receiving the maximal dosage, vitrectomy is indicated. For stage IIIb eyes, the
      maximal dosage should be administered first. If not efficacious, vitrectomy
      should be carried out before progression to stage IV.

PMID- 11313053
TI  - Comparison of scleral buckling and vitrectomy for retinal detachment resulting
      from flap tears in superior quadrants.
AB  - PURPOSE: To compare the surgical results of vitrectomy and scleral buckling for
      uncomplicated superior retinal detachment caused by flap tears. METHODS: Included
      in the study were 225 patients (225 phakic eyes) undergoing primary surgery by
      three surgeons between January 1990 and December 1996 for superior retinal
      detachment caused by flap tears (138 eyes by scleral buckling, 87 eyes by
      vitrectomy); all patients had been followed up for longer than 6 months after
      surgery. The choice of one of the two procedures was based on each surgeon's
      preference. The surgical outcome and the rate of complications were
      retrospectively compared between the two groups of eyes. RESULTS: Initial and
      final anatomical success rate were 92% and 100% after each procedure. Retinal
      redetachment after the initial procedure was due to new retinal breaks in 5 eyes,
      reopening of original breaks in 2 eyes of vitrectomy cases, and due to
      malpositioned buckle in 11 eyes of scleral buckling cases. Proliferative
      vitreoretinopathy occurred in 3 eyes of vitrectomy cases. CONCLUSION: Primary
      vitrectomy was as successful as scleral buckling for treating superior
      rhegmatogenous retinal detachment. Even though the high incidence of
      postoperative cataract formation was the major drawback, vitrectomy had some
      advantages over scleral buckling.

PMID- 11313054
TI  - Surgical excision versus laser photocoagulation for subfoveal choroidal
      neovascular membrane with age-related macular degeneration: comparison of visual
      outcomes.
AB  - PURPOSE: This study was designed to compare visual acuity after laser
      photocoagulation with visual acuity after surgical excision of the subfoveal
      choroidal neovascular membrane in patients with age-related macular degeneration
      (AMD). METHODS: We studied 54 patients (56 eyes) who underwent laser
      photocoagulation and 52 patients (52 eyes) who underwent surgical excision for
      new subfoveal choroidal neovascular membrane occurring with AMD. We compared mean
      log of minimal angle of resolution (MAR) visual acuity, and the percentages of
      eyes showing visual improvement and a visual acuity of 0.1 or better, between the
      two treatment groups at 12 months after treatment. The groups were also compared
      according to choroidal neovascular membrane size, ie, 1 disc diameter (DD) or
      smaller vs larger than 1 DD. RESULTS: Mean corrected visual acuity (P <.01),
      percentage of eyes with improved vision (P <.01), and percentage with a visual
      acuity of at least 0.1 (P <.01) were higher in surgically treated eyes. The
      differences in mean log MAR visual acuity and the percentages were significant
      only for choroidal neovascular membrane of one DD or less in size. CONCLUSIONS:
      Postoperative eyes, especially those with choroidal neovascular membranes 1 DD or
      less in size, had better visual outcomes. Patients who meet our eligibility
      criteria, especially with small choroidal neovascular membranes 1 DD or less in
      size, should undergo surgical excision.

PMID- 11313055
TI  - Magnifying prismatic lenses for vitrectomy.
AB  - PURPOSE: Viewing the fundus at higher magnification during vitrectomy makes
      surgical procedures much safer; however, the scope of magnification of the
      peripheral fundus has been limited. For better visualization of the periphery of
      the fundus, we have developed two new contact lenses called magnifying prismatic
      lenses. METHODS: The magnifying 15 degrees and 30 degrees prismatic lenses are
      made of a glass with a high index of refraction (n = 1.883). The lenses have a
      convex upper surface to provide a magnified view of the peripheral fundus.
      RESULTS: These magnifying 15 degrees and 30 degrees prismatic lenses provide an
      approximately 2x magnified view of the peripheral fundus. They also provide a
      more extensive view of the peripheral fundus than a regular (plano-concave)
      prismatic lens when the eye is tilted. CONCLUSION: The magnifying prismatic
      lenses are useful for viewing into the peripheral fundus with higher
      magnification.

PMID- 11313070
TI  - Course of hypochondriasis in an international primary care study.
AB  - Hypochondriasis is frequently defined as a chronic condition distinct from
      anxiety and depressive disorders. Consecutive primary care attenders (n=25,916)
      were screened using the General Health Questionnaire and a stratified random
      sample (n=5447) completed a baseline diagnostic assessment. All patients with
      significant psychiatric symptoms and a random sample of remaining patients
      (n=3201) were asked to complete a follow-up diagnostic assessment 12 months
      later. Of patients meeting an abridged definition of hypochondriasis at baseline,
      18% continued to do so at follow-up and an additional 16% continued to report
      hypochondriacal worries. 45% of those with hypochondriasis at follow-up also met
      criteria for DSM-IV anxiety or depressive disorder. Follow-up anxiety or
      depressive disorder was significantly associated with both onset and persistence
      of hypochondriasis. Hypochondriasis is moderately stable over time. The clear
      distinction between hypochondriasis and anxiety/depressive disorders suggested by
      ICD-10 and DSM-IV may be difficult to accomplish in practice.

PMID- 11313071
TI  - The association between depressive symptoms and health status in patients with
      chronic pulmonary disease.
AB  - This study evaluated the association between depressive symptoms and health
      related quality of life (HRQoL) in patients with chronic pulmonary disease using
      both general and disease-specific HRQoL measures. A cross-sectional analysis of
      HRQoL measures completed by patients enrolled in the Department of Veteran
      Affairs Ambulatory Care Quality Improvement Project. 1252 patients with chronic
      pulmonary disease screened positive for emotional distress and returned the
      Hopkins Symptom Checklist-20 (SCL-20). 733 of 1252 had a score of 1.75 or greater
      on the SCL-20 indicating significant depressive symptoms. Depressive symptoms
      were associated with statistically significantly worse general and pulmonary
      health as reflected by lower scores on all sub-scales of both the Medical
      Outcomes Short Form-36 and the Seattle Obstructive Lung Disease Questionnaire. In
      fact, 11% to 18% of the variance in physical function sub-scales was attributed
      to depressive symptoms alone. Patients with chronic pulmonary disease and
      depressive symptoms reported significantly more impaired functioning and worse
      health status when compared to those patients without depressive symptoms.
      Because there are highly effective treatments for depression, selective screening
      of patients with chronic pulmonary disease for depression may identify a group
      that could potentially benefit from treatment interventions.

PMID- 11313072
TI  - Posttraumatic stress disorder after pregnancy loss.
AB  - This prospective longitudinal study investigated the prevalence of posttraumatic
      stress disorder (PTSD) in response to pregnancy loss. About 1,370 women were
      recruited in the early stages of pregnancy and 113 of them had a subsequent
      pregnancy loss. One and four months after pregnancy loss, they were assessed for
      PTSD with the Posttraumatic Symptom Scale. Depression was also assessed. The
      majority had an early loss, i.e., within 20 weeks. At one month, the prevalence
      of PTSD was 25%, and the symptom-severity was similar to other traumatized
      populations. Women with PTSD had increased risk of depression: 34% of PTSD cases
      and 5% of non-cases reported depression. At four months, 7% met the criteria for
      PTSD, of which half were chronic. In contrast, rates for depression had not
      declined. The results indicate that pregnancy loss is potentially traumatic,
      putting women at risk of developing PTSD. In most cases, the disorder is
      immediate and persists for several months.

PMID- 11313073
TI  - Financial management challenges for general hospital psychiatry 2001.
AB  - Psychiatry programs are facing significant business and financial challenges.
      This paper provides an overview of these management challenges in five areas:
      departmental, hospital, payment system, general finance, and policy. Psychiatric
      leaders will require skills in a variety of business management areas to ensure
      their program success. Many programs will need to develop new compensation models
      with more of an emphasis on revenue collection and overhead management. Programs
      which cannot master these areas are likely to go out of business. For academic
      programs, incentive systems must address not only clinical productivity, but
      academic and teaching output as well. General hospital programs will need to
      develop increased sophistication in differential cost accounting in order to be
      able to advocate for their patients and program in the current management
      climate. Clinical leaders will need the skills (ranging from actuarial to
      negotiations) to be at the table with contract development, since those decisions
      are inseparable from clinical care issues. Strategic planning needs to consider
      the value of improving integration with primary care, along with the ability to
      understand the advantages and disadvantages of risk-sharing models. Psychiatry
      leaders need to define and develop useful reports shared with clinical division
      leadership to track progress and identify problems and opportunities. Leaders
      should be responsible for a strategy for developing appropriate information
      system architecture and infrastructure. Finally, it is hoped that some leaders
      will emerge who can further our needs to address inequities in mental health fee
      schedules and parity issues which affect our program viability.

PMID- 11313074
TI  - A combined ethics & psychiatric consultation.
AB  - A case presentation is used to illustrate how psychiatrists can contribute to
      clinical ethics. A 75-year-old man with end-stage COPD was admitted to the ICU.
      His condition deteriorated and he lost decision-making capacity without
      expressing his wishes about end-of-life care. Although he no longer needed care
      in the ICU his surrogate decision-maker objected to his being transferred. Seven
      months after the patient's admission an ethics consultation was carried out by a
      psychiatrist-ethicist. The following issues are discussed, elaborating on points
      previously made by the authors [1,2]: the absence of an advance directive,
      surrogate decision-making, the allocation of ICU beds, guidelines for discharge
      from the hospital, the lateness of the ethics consultation, and the interweaving
      of ethical questions with psychiatric factors. The psychiatrist-ethicist was
      ideally suited to address all these issues and to make a significant contribution
      to the care of the patient and his family.

PMID- 11313075
TI  - Depression, anxiety comorbidity, and disability in tuberculosis and chronic
      obstructive pulmonary disease patients: applicability of GHQ-12.
AB  - Our aim was to study anxiety and/or depression comorbidity and the influence of
      these comorbid conditions on disability for 3 clinical groups of pulmonary
      tuberculosis and chronic obstructive pulmonary disease (COPD). We also
      investigated the applicability of General Health Questionnaire 12 (GHQ12) for
      these clinical groups as a simple screening test for psychiatric comorbidity. A
      total of 157 male inpatients were included in the study: 42 with recently
      diagnosed (RDtb), 39 with defaulted (Dtb), 39 with multidrug resistant
      tuberculosis (MDRtb) and 38 with COPD. The presence of depression and anxiety was
      assessed by Composite International Diagnostic Interview (CIDI). Disability was
      evaluated by Brief Disability Questionnaire. The validity of GHQ12 for the study
      groups was examined in order to determine a functional cut-off point. Depression
      and/or anxiety comorbidity was 19% for RDtb, 21.6% for Dtb, 25.6% for MDRtb and
      47.3% for COPD. Patients with psychiatric comorbidity had higher disability
      scores than the group without psychiatric comorbidity. For the tuberculosis group
      a 3/4 cut-off point of GHQ had 80.7% sensitivity and 87.1% specificity while a
      5/6 cut-off point with 83.3% sensitivity and 80% specificity was applicable to
      the COPD group.

PMID- 11313076
TI  - Preoperative risk factors for postoperative delirium.
AB  - The objective of this article was to estimate the incidence of delirium in a
      sample of patients undergoing elective surgery and to identify the preoperative
      factors most closely associated with developing this complication. Consecutive
      patients (n=500) underwent a full preoperative medical evaluation including
      assessment of cognitive and functional status. Daily evaluation on postoperative
      days 1 through 4 included medical record review and direct standardized patient
      interviews. Logistic regression was used to explore the associations between
      preoperative factors and postoperative delirium. Delirium was detected in 57
      (11.4%) patients. Univariate factors associated with delirium included age> or
      =70 years (RR=3.1 [1.75,5.55]), preexisting cognitive impairment (RR=3.1 [1.73,
      5.43]), greater preoperative functional limitations (RR=1.57 [1.27, 1.94]), and a
      history of prior delirium (RR 4.1 [1.98 to 8.27]. Adjusting for other factors,
      previous delirium (OR=4.08 [1.85, 9.0]), age> or =70 years (OR=3.2 [1.6, 6.0],
      and preexisting cognitive impairment (OR=2.16 [1.15, 4.0] remained predictive of
      delirium. Patients' perceptions that alcohol had affected their health (OR=6.53
      [1.58 to 28.1]) and use of narcotic analgesics just prior to admission (OR=2.7
      [1.37 to 5.3]) were also significantly associated with delirium postoperatively.
      Several easily obtained preoperative clinical factors can be used to identify
      patients at risk for postoperative delirium. This approach, when combined with
      specialized delirium teams using established guidelines, may be more effective in
      targeting patients at risk, thus reducing the number of episodes and days of
      delirium.

PMID- 11313077
TI  - The relationship between cognitive performance and employment and health status
      in long-term survivors of the acute respiratory distress syndrome: results of an
      exploratory study.
AB  - Survivors of acute respiratory distress syndrome (ARDS) are at risk for long
      lasting cognitive decline due to hypoxemia, sepsis and/or psychological sequelae
      associated with aggressive supportive care in the intensive care unit (ICU). We
      conducted an exploratory study to assess cognitive performance in long-term
      survivors of ARDS and to investigate how cognitive functioning is related to
      employment status and health-related quality of life (HRQOL). At median time of
      6.0 years after ICU discharge, forty-six ARDS survivors were tested with SKT, a
      short cognitive performance test for assessing deficits of memory and attention.
      A measure of HRQOL (SF-36 Health Status Questionnaire) was also administered, and
      in a brief psychiatric interview, employment status was rated. 23.9% (n=11) of
      the patients showed cognitive impairments. However, no extreme and severe
      cognitive deficits were recorded. They primarily revealed low levels of cognitive
      function in various tasks assessing attention skills. Disability was found in
      41.3% (n=19) of the patients. All ARDS survivors with cognitive deficits were
      disabled, whereas only 22.9% (n=8) of the cognitively not impaired patients gave
      evidence of disability. The SF-36 values of the ARDS survivors indicated impaired
      health status on seven out of eight domains when compared to normative population
      data. Patients with cognitive deficits described the lowest HRQOL with major
      limitations in the domains role-physical and social functioning when compared to
      patients without cognitive impairments. In conclusion, long-term ARDS survivors
      exhibit impaired health status and the presence of cognitive deficits is
      associated with disability and considerable impairments in HRQOL. More detailed
      psychiatric research is required to establish the etiology of these cognitive
      impairments.

PMID- 11313078
TI  - The effects of tryptophan depletion on mood and psychiatric symptoms.
AB  - BACKGROUND: The number of studies using tryptophan depletion (TD) challenge has
      increased markedly in the past few years. Recently, a number of negative results
      have been published, implicating that the effect of TD on mood may be less
      consistent than previously thought. METHODS: The literature on the mood effects
      of TD in psychiatric patients and healthy volunteers was reviewed. RESULTS: TD
      has a mood-lowering effect in subgroups of recovered depressed patients, patients
      with seasonal affective disorder and vulnerable healthy subjects. The mood effect
      in former patients is of a different quality, however, than the effect in healthy
      subjects. Some recent negative studies in depression might be explained by
      insufficient lowering of plasma tryptophan levels. Preliminary evidence exists
      for an effect of TD on bulimia nervosa, autism, aggression and substance
      dependence. CONCLUSIONS: The effects of TD on mood may be more consistent than
      suggested by a number of recent negative studies. Response to TD in recovered
      depressed patients is associated with prior treatment. However, even in SSRI
      treated patients the relapse rates are not higher than 50-60%, which needs to be
      explained. The clinical usefulness of the response to TD in recovered patients
      (prediction of relapse after treatment discontinuation) and in symptomatic
      patients (prediction of treatment refractoriness) deserves more research
      attention. Further suggestions for future research include the cognitive effects
      of TD in recovered depressed patients and the effect of dietary habits on
      response to TD.

PMID- 11313079
TI  - Heterogeneity of childhood conduct disorder: further evidence of a subtype of
      conduct disorder linked to bipolar disorder.
AB  - BACKGROUND: Although a small literature suggests that conduct disorder (CD) co
      occurs with bipolar disorder (BPD), little is known about this overlap. Thus, we
      investigated the familial association of antisocial disorders (CD and/or
      antisocial personality disorder (ASPD)) and BPD among the first degree relatives
      of children with CD with and without comorbid BPD. METHODS: We compared relatives
      of four proband groups defined by the presence or absence of CD and BPD in the
      proband: (1) CD+BPD (N=26 probands, 92 relatives; (2) BPD without CD (BPD) (N=19
      probands, 53 relatives); (3) CD without BPD (CD) (N=16 probands, 58 relatives);
      and (4) controls without BPD or CD (N=102 probands, 338 relatives). All subjects
      were evaluated with structured diagnostic interviews. Diagnoses of relatives were
      made blind to the diagnoses of probands. RESULTS: The results show high rates of
      antisocial disorders and BPD in relatives of children with CD+BPD. Moreover,
      antisocial disorders and BPD cosegregated among the relatives of children with
      CD+BPD. While relatives of both CD proband groups with and without BPD had high
      rates of CD/ASPD, the combined condition CD/ASPD+BPD was found exclusively among
      relatives of probands with CD+BPD. LIMITATIONS: Since we pooled two datasets,
      subjects were not all evaluated at the same time. Also, the lack of direct
      psychiatric interviews with children younger than 12 may have decreased the
      sensitivity of some diagnoses. CONCLUSIONS: These family-genetic findings suggest
      that CD and BPD represent separate disorders. Furthermore, they suggest that the
      comorbid condition of CD+BPD may be a distinct nosological entity. This suggests
      that clinicians treating CD or BPD children should consider the treatment
      implications of this comorbid condition.

PMID- 11313080
TI  - Is interpersonal sensitivity specific to non-melancholic depressions?
AB  - BACKGROUND: We investigated whether melancholic and non-melancholic Japanese
      depressive patients differed in regard to a personality feature, interpersonal
      sensitivity, as measured by the Interpersonal Sensitivity Measure (IPSM).
      METHODS: In addition to 154 normal controls, 66 remitted melancholic patients and
      55 remitted non-melancholic patients filled out the IPSM and two widely-used
      comprehensive personality inventories, the Temperament and Character Inventory
      (TCI) and the Munich Personality Test (MPT). The subdivision of patients was made
      according to three major symptom-based criteria for melancholia (those of RDC,
      DSM-III, DSM-IV). RESULTS: Multivariate and post-hoc univariate analyses of
      variance revealed significant differences among the three groups in several
      personality dimensions after Bonferroni's adjustments of P values. While reported
      scores of both melancholic and non-melancholic patients deviated from normative
      scores on several personality dimensions, non-melancholic patients reported
      significantly higher scores on the total IPSM and the 'fragile inner-self' (a
      subscore of the IPSM) than did normal controls or melancholic depressives. The
      principal component analysis isolated two factors related to depressive
      disorders: one factor corresponding to the five IPSM scores; and the other
      corresponding to harm avoidance, neuroticism and frustration tolerance. The
      scores on the former factor differentiated non-melancholic depressives from
      melancholic depressives and normal controls. The scores on the latter factor
      differentiated both melancholic and non-melancholic depressives from normal
      controls. LIMITATIONS: Prospective studies in which depressive subjects are
      subdivided into melancholic and non-melancholic subjects will be required to see
      whether the personality deviations here related to depressive disorders strongly
      reflect the premorbid personality function. CONCLUSIONS: These results indicate
      that the IPSM scales (particularly, the fragile inner-self scale and the total
      IPSM scale) are relatively independent of all dimensions included in the two
      comprehensive personality inventories, and have a capability to describe
      personality differences between non-melancholic depression and melancholia.

PMID- 11313081
TI  - Seasonality and affective disorders: a report from North India.
AB  - Case records of the patients with major affective disorders (ICD-10 criteria),
      seen over a 5 year period in a busy clinic in North India were examined for
      Seasonal Affective Disorder (SAD) as per DSM-III-R criteria. In addition,
      seasonality of episodes of all affective disorders was also studied. Around 5.67%
      of the cases (n=44) retrospectively met the DSM-III-R criteria of SAD and
      predominant pattern was that of summer depression (n=18). There was also a
      consistent pattern of seasonal mania either in conjunction with seasonal
      depression (n=18) or in form of seasonal recurrent mania (n=11). None of the
      cases of depression showed any atypical vegetative features. In cases not meeting
      criteria for SAD (n=731), there was a trend for peaks for depressive episodes in
      winter followed by a smaller peak in summer months while manic episodes had peaks
      towards rainy and winter months. As compared to seasonal patterns of affective
      disorders in temperate zones, there was a general trend for opposite patterns of
      seasonality in SAD as well as in non-SAD. The findings are discussed in context
      of the climatic conditions of North India.

PMID- 11313082
TI  - Adolescent depression: the role of discontinuities in life course and social
      support.
AB  - OBJECTIVE: To study sociodemographic determinants of depression among 14-16 years
      old girls and boys, and the role of perceived social support in mediating the
      effects of the background variables. METHOD: 16464 adolescents aged 14-16
      participated the School Health Promotion Study, a survey about health, health
      behaviour and school behaviour. Depression was measured by the Finnish
      modification of the 13-item Beck Depression Inventory. Moderate to severe
      symptoms in this scale were recorded as depression. RESULTS: Depression was
      associated with family structure in both sexes. Among girls, having moved
      recently and low parental education increased the risk for depression, among
      boys, unemployment in the family. Accumulating number of discontinuities in life
      course increased the proportion of the depressed among both girls and boys.
      Perceived lack of social support had the same effect. Lack of support did not
      explain the effect on depression of the discontinuities in life course.
      CONCLUSION: To detect risk groups for adolescent depressive disorders, health
      services should pay attention to adolescents who have experienced life changes.
      Perceived social support should be enquired.

PMID- 11313083
TI  - Patterns of psychoactive substance detection from routine toxicology of suicides
      in Mobile, Alabama, between 1990 and 1998.
AB  - BACKGROUND: Postmortem toxicology can be useful for reconstructing some
      clinically important events occurring before a suicide. Its utility may be
      improved by examining patterns of detected substances in a population over time.
      METHODS: Toxicology was performed for 333 (96%) of the 346 suicides occurring in
      Mobile County, Alabama, between October 1990 and September 1998. Detected
      psychoactive substances were grouped in three categories: alcohol, cocaine, and
      cannabis; abusable prescription medications; and non-abused psychotropic
      medications. The overlap between these three categories was assessed. RESULTS:
      Psychoactive substances were detected in 227 (68%) of 333 suicides. Of the cases
      positive for any prescription psychoactive medication, 2/3 were positive for an
      abusable medication. An abusable substance was found in 56% of cases positive for
      non-abused psychotropic medication. Alcohol, cocaine and/or cannabis were found
      in 34% of cases with abusable prescription medications and in 33% with non-abused
      psychotropics. LIMITATIONS: Clinicians must be aware of a number of
      methodological realities when interpreting routine postmortem toxicology results.
      CONCLUSIONS: Routine surveillance of psychoactive substances among suicides can
      provide useful data for directing and monitoring strategies for suicide
      prevention in clinical practice.

PMID- 11313084
TI  - Validation of the Edinburgh Postnatal Depression Scale for men, and comparison of
      item endorsement with their partners.
AB  - BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) has been validated
      and used extensively in screening for depression in new mothers, both in English
      speaking and non-English speaking communities. While some studies have reported
      the use of the EPDS with fathers, none have validated it for this group, and thus
      the appropriate cut-off score for screening for depression or anxiety caseness
      for this population is not known. METHODS: Couples were recruited antenatally and
      interviewed at six weeks postpartum. EPDS scores and distress caseness
      (depression or anxiety disorders) for 208 fathers and 230 mothers were determined
      using the Diagnostic Interview Schedule. RESULTS: Analyses of the EPDS for
      fathers using distress caseness (depression or anxiety disorders) as the
      criterion shows that a cut-off of 5/6 has optimum receiver operating
      characteristics. Furthermore acceptable reliability (split-half and internal
      consistency) and validity (concurrent) coefficients were obtained. For mothers
      the optimum cut-off screening value to detect distress caseness was 7/8. Item
      analysis revealed that fathers endorsed seven of the ten items at lower rates to
      mothers, with the most significant being that referring to crying. CONCLUSIONS:
      The EPDS is a reliable and valid measure of mood in fathers. Screening for
      depression or anxiety disorders in fathers requires a two point lower cut-off
      than screening for depression or anxiety in mothers, and we recommend this cut
      off to be 5/6.

PMID- 11313085
TI  - Effects of symptomatic severity on elevation of plasma soluble interleukin-2
      receptor in bipolar mania.
AB  - BACKGROUND: Circulating soluble interleukin-2 receptors (sIL-2Rs) and soluble
      interleukin-6 receptors (sIL-6Rs) are stable immune measures. Elevated plasma sIL
      2R levels are present in patients with schizophrenia, major depression, and
      bipolar mania, but not with minor psychiatric disorders. The increased plasma sIL
      2R levels are state-dependent in bipolar mania. However, altered production of
      plasma sIL-6R and the effects of clinical characteristics on plasma sIL-6R and
      sIL-2R levels in bipolar disorder remains uncertain. METHODS: Plasma sIL-2R and
      sIL-6R levels were measured in 31 Taiwanese bipolar manic (DSM-IV) patients with
      Young Mania Rating Scale (YMRS) scores of > or =26 as well as during the
      subsequent remission (YMRS< or =12), and equal numbers of age- and gender-matched
      healthy controls. The relationships of clinical variables such as age, age of
      onset, smoking, medication status, coexisting psychotic features, number of prior
      episodes, duration of illness, presence of depression before or following the
      manic episode, and manic severity to plasma sIL-2R and sIL-6R levels in acute
      mania along with remission were examined. RESULTS: Plasma sIL-2R but not sIL-6R
      levels were significantly higher in acute mania than in subsequent remission
      (P<0.05) and controls (P<0.0005). In acute mania, the plasma sIL-2R levels were
      significantly correlated to YMRS scores (r=0.34, P<0.05). The remaining clinical
      variables had no effect on plasma sIL-2R and sIL-6R levels in acute mania or
      remission. There was a significantly positive relationship between the reduction
      of plasma sIL-2R levels from the acute to follow-up measurements (DeltasIL-2R)
      and symptomatic improvement of acute mania (DeltaYMRS) (r=0.61, P<0.001).
      LIMITATIONS: Our sample included medicated and unmedicated patients in acute
      mania. The psychotropic medication may have divergent effects on the plasma sIL
      2R levels in acute mania and subsequent remission. CONCLUSIONS: Elevation of
      plasma sIL-2R but not sIL-6R levels in bipolar mania supports the idea that the
      immunomodulatory mechanism may vary in different psychotic disorders. In contrast
      to being a trait marker in schizophrenia and depressive disorder, plasma sIL-2R
      levels may be considered a biological indicator of manic severity in a group of
      bipolar affective patients.

PMID- 11313086
TI  - Suicide probability and psychological morbidity secondary to HIV infection: a
      control study of HIV-seropositive, hepatitis C virus (HCV)-seropositive and
      HIV/HCV-seronegative injecting drug users.
AB  - BACKGROUND: Suicide ideation and psychological morbidity among HIV-positive
      patients has been the object of intense research. No study has investigated this
      area among injecting drug users (IDUs) infected with HIV and those infected with
      the hepatitis C virus (HCV), which has the same patterns of transmission of the
      HIV and may favour HIV replication and, possibly, HIV disease progression.
      METHODS: In order to examine the prevalence and characteristics of suicide
      ideation and psychological morbidity associated with HIV and HCV infection in
      IDUs, a sample of HIV+ (n=81), HIV-/HCV+ (n=62) and HIV-/HCV- (n=152) subjects
      completed the Suicide Probability Scale (SPS), The Brief Symptom Inventory (BSI)
      and the Hospital Anxiety and Depression Scale (HADS). RESULTS: No difference was
      found between the groups as far as the mean scores on SPS and the risk of suicide
      (no-low risk category: 70.7% HIV+, 56.09% HCV+, 65.6% HIV-/HCV-). Estimated
      psychological morbidity (BSI) (26.9% HIV+, 27.1% HCV+, 25.4% of HIV-/HCV-) and
      BSI and HADS scores were comparable across the groups. CONCLUSIONS: Suicide
      ideation, psychological morbidity and anxiety and depression symptoms seemed not
      to be directly influenced by HIV-serostatus. Careful assessment of psychological
      symptoms and suicide ideas among IDUs, as a vulnerable segment of population at
      risk of HIV and HCV infections, needs to be routinely carried out in clinical
      settings.

PMID- 11313087
TI  - A comparison between the Beck Depression Inventory (BDI) and the self-rating
      version of the Montgomery Asberg Depression Rating Scale (MADRS).
AB  - BACKGROUND: The Beck Depression Inventory BDI is the most often used self-rating
      instrument for depressive symptoms. In the present study, the BDI was compared
      with a self-rating version of the Montgomery Asberg Depression Rating Scale
      (MADRS-S) in 86 psychiatric patients with mainly affective and anxiety disorders.
      METHODS: The patients were interviewed with the SCID-I Interview for a DSM-IV
      Major depression, and self-assessed the BDI and the MADRS. They were rated to
      have either mild, moderate or severe depressive symptomatology. After recovery,
      criteria for DSM-IV Personality disorders were self-assessed. RESULTS: The
      instruments were about equal in differentiating between different Axis-I
      diagnoses and did not differ according to sensitivity to change during
      antidepressive treatment. Although the scales were highly intercorrelated
      (r=0.869), the BDI was demonstrated to tap more maladaptive personality traits
      compared to the MADRS-S. LIMITATIONS: Because the sample consisted of psychiatric
      patients with prominent psychiatric symptomatology, the discriminative power of
      the BDI and the MADRS-S should be further evaluated in a sample with milder
      symptoms. CONCLUSIONS: The MADRS-S is equivalent to the BDI as a self-assessment
      instrument for depression, but the MADRS-S focuses on core depressive symptoms,
      and is less influenced by maladaptive personality traits.

PMID- 11313088
TI  - Combining psychotherapy and antidepressants in the treatment of depression.
AB  - OBJECTIVE: To compare the efficacy of antidepressants with that of
      antidepressants plus psychotherapy ("combined therapy") in the treatment of
      depression. METHODS: 6 month randomised clinical trial of antidepressants (N=84)
      and combined therapy (N=83) in ambulatory patients with Major Depression and a 17
      item HDRS baseline score of at least 14 points. The antidepressant protocol
      provides for three successive steps in case of intolerance or inefficacy:
      fluoxetine, amitriptyline and moclobemide. The combined therapy condition
      consists, in addition to pharmacotherapy, of 16 sessions of Short Psychodynamic
      Supportive Psychotherapy. Efficacy is assessed using the 17-item HDRS, the CGI of
      Severity and of Improvement, the depression subscale of the SCL-90, and the
      Quality of Life Depression Scale. The data analysis is conducted on three
      samples: the intention-to-treat sample, the per protocol sample and the observed
      cases sample. RESULTS: After randomisation, 32% of the patients refused the
      proposed pharmacotherapy while 13% refused the proposed combined therapy. In 24
      weeks, 40% of the patients who started with the pharmacotherapy stopped
      medication; 22% of those receiving the combined therapy did so. The difference in
      success rates is statistically significant, favouring combined therapy, in 23%,
      31% and 62% of the patients after 8, 16 and 24 weeks of treatment, respectively.
      At week 24, the mean success rate is 40.7% in the pharmacotherapy group and 59.2%
      in the combined therapy group. CONCLUSION: Patients found combined treatment
      significantly more acceptable, they were significantly less likely to drop out of
      combined therapy and, ultimately, significantly more likely to recover. Combined
      therapy is preferable to pharmacotherapy in the treatment of ambulatory patients
      with major depression.

PMID- 11313089
TI  - Maintenance desipramine for dysthymia: a placebo-controlled study.
AB  - BACKGROUND: This study examines the efficacy of maintenance pharmacotherapy in
      dysthymia without concurrent major depression, i.e. 'pure dysthymia'. No
      published data exist on this topic. METHODS: Responders to a 10-week open trial
      of desipramine (DMI) whose therapeutic response persisted during a 4-month
      continuation phase were eligible to begin a 2-year placebo-controlled maintenance
      phase. We analyzed the subgroup with DSM-III-R pure dysthymia (n=27) that entered
      maintenance. Time to recurrence during maintenance therapy was compared between
      the two treatment groups. RESULTS: Six of 13 patients receiving placebo and none
      of 14 patients receiving ongoing DMI experienced a recurrence. Risk of recurrence
      was significantly greater for placebo patients. Five of six placebo recurrences
      occurred within the first 6 months of maintenance. LIMITATIONS: Larger
      replication studies are needed. CONCLUSION: Desipramine was efficacious as a
      maintenance treatment in patients with pure dysthymia who responded to 7 months
      of acute and continuation DMI.

PMID- 11313090
TI  - Differences in symptomatology and diagnostic profile in younger and elderly
      depressed inpatients.
AB  - BACKGROUND: Depression is the most prevalent psychiatric disorder in the elderly
      and several studies indicate that 10-15% of persons over 65 years suffer from
      significant depressive symptoms. Despite the high prevalence, most cases of
      depression in the elderly remain unrecognized and untreated, maybe because of a
      different pattern of symptoms across age groups. The objective of the study was
      to compare symptomatology and diagnostic profile between younger and elderly DSM
      III and DSM-III-R major depressed inpatients and to advise an appropriate
      depression scale for the elderly. METHODS: The study covers 461 depressed
      inpatients evaluated with the Hamilton Depression Scale and the Newcastle 1965
      Scale. To find differences between younger and elderly patients, the
      symptomatology was analyzed stepwise by principal component analyses, latent
      structure analyses and single item analyses. RESULTS: No clinically significant
      differences in symptomatology between younger and elderly depressed patients were
      found. The DSM-IV concept of Major Depression and the ICD-10 criteria for
      depression was not influenced by patients' age. LIMITATIONS: All patients were
      hospitalized and mainly endogenously depressed and generalization of the results
      to other populations should be made with caution. Only pretreatment data was
      analyzed. CONCLUSIONS: The DSM-IV concept of Major Depression and the ICD-10
      criteria for depression can be used without modification for age.

PMID- 11313091
TI  - Divalproex sodium in sex offenders with bipolar disorders and comorbid
      paraphilias: an open retrospective study.
AB  - BACKGROUND: This study evaluated divalproex response in sex offenders with a
      bipolar disorder. METHODS: We reviewed the records of all sex offenders who
      participated in a residential rehabilitative program who received divalproex for
      treatment of a bipolar disorder. Patients' mood symptoms and, when present,
      comorbid paraphilic symptoms, were retrospectively assessed using the CGI
      severity scale. RESULTS: Sex offenders displayed significant improvement in manic
      symptoms with divalproex treatment. However, there was no significant improvement
      in paraphilic symptoms in the subset of patients admitting to these symptoms.
      CONCLUSION: Divalproex may be effective for manic symptoms in sex offenders with
      a bipolar disorder. However, for bipolar sex offenders with comorbid paraphilias,
      the drug may not be effective for paraphilic symptoms. LIMITATIONS: This study
      was limited by its retrospective, open-label design, lack of systematic means of
      assessing manic and paraphilic symptoms, and small sample size. CLINICAL
      RELEVANCE: Divalproex may be a helpful adjunct in the treatment of the subset of
      sex offenders who have a bipolar disorder.

PMID- 11313092
TI  - Patterns of response to repeated total sleep deprivations in depression.
AB  - BACKGROUND: Patterns of response and nonresponse in repeated sleep deprivation
      (SD) are of both clinical and scientific interest; as yet, studies have yielded
      inconsistent results. METHODS: Eighteen inpatients suffering from a major
      depression were subjected to a series of six scheduled total sleep deprivations
      within 3 weeks; 12 of them completed the whole protocol. All were under a
      constant antidepressant medication with amitriptyline. SD effects were measured
      using observer and self rating scales. RESULTS: Each single SD led to a
      significant improvement. Of the 12 patients who completed the protocol, seven
      were classified as responders at endpoint (i.e., 1 week after the sixth TSD). The
      majority of patients exhibited a pattern of responses and nonresponses randomly
      distributed over time. There was no temporal trend. The initial effect did not
      predict the average response to the following SDs. LIMITATIONS: One third of
      patients dropped out before completing the protocol which limits the scope of the
      study. CONCLUSIONS: Response to a single SD is not generalizable on a series of
      following SDs in an individual. The mechanism of action of SD does probably not
      involve mechanisms subjected to habituation or sensitization.

PMID- 11313093
TI  - Predictors of response to lithium augmentation in tricyclic antidepressant
      resistant depression.
AB  - BACKGROUND: The efficacy of lithium augmentation in therapy-resistant depression
      has been shown in a series of well-designed, placebo-controlled studies. However,
      little is known about the predictors of a good response to this treatment
      strategy. METHODS: We retrospectively examined the predictive value of 20
      demographic, clinical, biochemical and endocrinological variables using a two
      step logistic regression. Seventy-one in-patients with depression refractory to
      tricyclic antidepressants had received lithium augmentation as part of a
      standardised treatment protocol. RESULTS: Within 4 weeks 37 patients (52%)
      responded to lithium augmentation. Five variables with predictive value were
      found. Responders were more severely depressed according to the Bech-Rafaelsen
      Melancholia Scale. The duration of their index episode was shorter.
      Triiodothyronine serum levels were lower and neuroleptic co-medication and co
      diagnosis of personality disorder were less frequent. LIMITATIONS: This was an
      open, retrospective study. CONCLUSIONS: Severity of depression is a predictor of
      response to lithium augmentation. This result conflicts with recent studies but
      is similar to results found in studies of other pharmacological antidepressant
      strategies.

PMID- 11313094
TI  - A factor analysis of signs and symptoms of the manic episode with Bech-Rafaelsen
      Mania and Melancholia Scales.
AB  - BACKGROUND: Several factor analyses of signs and symptoms of mania have been
      reported using different rating scales. We propose here that the use of two
      instruments well known in the European literature may be useful in detecting the
      structure of manic episodes. METHOD: We investigated the pattern of symptoms in a
      group of 124 bipolar inpatients hospitalised for a manic episode. We conducted a
      factor analysis of the broad range of psychiatric symptoms covered by the Bech
      Rafaelsen Mania Scale (BRMaS) and Melancholia Scale (BRMeS). RESULTS: Five eigen
      values were greater than unity, which determined the number of factors computed.
      The five factors captured 66.7% of the total variance. Following rotation, five
      factors were clinically relevant. CONCLUSION: This suggests that both euphoric
      activation and depression are prominent in this sample.

PMID- 11313095
TI  - Modest adjunctive benefit with transcranial magnetic stimulation in medication
      resistant depression.
AB  - BACKGROUND: Controverted results have been obtained using high frequency
      transcranial magnetic stimulation (HF-rTMS) as an antidepressant treatment.
      METHODS: Forty patients suffering from drug-resistant major depression received
      ten sessions of HF-rTMS at 90% of the motor threshold on the left prefrontal
      cortex or sham stimulation, added to their pharmacological treatment, in a
      randomized double-blind design. In a second open phase, patients still fulfilling
      criteria of inclusion received ten additional sessions of HF-rTMS at 90 or 110%.
      RESULTS: Real, but not sham HF-rTMS, was associated with a significant decrease
      in the Hamilton Depression Rating Scale, but only twelve patients decreased more
      than 50%. CONCLUSIONS: Left prefrontal HF-rTMS was effectively associated with
      antidepressant treatment, although the size effect was small. LIMITATIONS:
      Shortage of the sample and control difficulties of the placebo effect. CLINICAL
      RELEVANCE: Questionable in more than half of the patients studied.

PMID- 11313096
TI  - Mental health literacy: an impediment to the optimum treatment of major
      depression in the community.
AB  - BACKGROUND: Mental health literacy refers to the knowledge and beliefs about
      mental disorders which aid their recognition, management and prevention. This
      study examined the mental health literacy and experience of depression in a
      random and representative community population. METHODS: The experience of
      depression and mental health literacy of 3010 subjects from a random and
      representative population were determined on the basis of responses to the mood
      module of the PRIME-MD and questions about a vignette of a person with features
      of major depression. RESULTS: Those with major depression had significantly more
      personal experience of depression than those with other depressions and those who
      were not depressed, but there were few significant differences between the groups
      in terms of mental health literacy. Of those with major depression, 40%
      considered anti-depressants helpful, but 40% also considered they were harmful.
      CONCLUSIONS: There is a considerable impediment to the recognition and management
      of major depression and a need for further community education programs.

PMID- 11313097
TI  - Behavioral social support between remitted depressed patients with partners and
      strangers.
AB  - BACKGROUND: Social support is associated with depression outcome and is effected
      by observable behaviors that express involvement. METHODS: Eleven remitted
      depressed patients were studied during a social interaction with their partner
      and a similar interaction with a stranger, matched on the sex and age of the
      partner. RESULTS: The patient-partner interaction displayed lower levels of
      involvement as compared to the patient-stranger interaction despite successful
      treatment for depression. CONCLUSION: It is suggested that the findings are
      reflective of the continuing depressogenic process. LIMITATIONS: A healthy
      control group for the patient-partner group was not employed. CLINICAL RELEVANCE:
      Behavioral interactions between patients and partners may require as much
      attention during treatment as depressive symptomology alone.

PMID- 11313099
TI  - Immunosenescence and cancer: a review.
AB  - The human neoplastic pathologies are age-dependent. The increased occurrence of
      tumors observed with advancing age may be determined by the accumulation of
      certain phenomena promoting different phases of neoplastic processes. In these
      events, important roles can be attributed to mutations of the genome that
      accumulate during aging and to the immunosenescence. It may be hypothesized that
      certain tumors controlled by the immune system may become more frequent in the
      elderly as a consequence of the decreased functionality of this important defense
      system of the organism. Nevertheless, the problems of the interrelationships
      between the immunosenescence and tumors are seriously contradictory. Therefore,
      on the one hand, one has to establish how much the immunodeficit of the elderly
      patient may be responsible for the neoplastic pathology, while on the other hand,
      one cannot neglect important environmental and pathophysiological factors in
      these cases.

PMID- 11313098
TI  - Serotonin-induced platelet intracellular calcium mobilization in various
      psychiatric disorders: is it specific to bipolar disorder?
AB  - BACKGROUND: Serotonin (5-HT)-stimulated platelet intracellular calcium (Ca)
      mobilization has been reported to be enhanced in unmedicated depressive patients
      compared to those of normal healthy subjects, which suggests increased 5-HT2A
      receptor function in these patients. It has not been ascertained whether this
      enhanced response is specific to some type of affective disorders among various
      mental disorders. METHODS: We examined 5-HT-induced platelet intracellular Ca
      response in 152 unmedicated outpatients with various psychiatric disorders
      including bipolar disorder (BD), major depressive disorder with melancholia (DM),
      major depressive disorder without melancholia (DN), schizophrenia (SCH), panic
      disorder (PD), obsessive-compulsive disorder (OCD), social phobia (SP) and
      bulimia nervosa (BN), and 30 normal controls. RESULTS: We observed no significant
      differences in basal intracellular Ca concentration among all patient subgroups
      and normal controls. While the 5-HT-induced Ca response was significantly and
      specifically higher in patients with BD than in normal controls, no significant
      differences were found in the Ca response to 5-HT between patients with DM, DN,
      SCH, PD, OCD, SP and BN, and normal controls. LIMITATIONS: The sample sizes of
      each group are still small. Therefore, they have to be enlarged in the
      continuation of the study so as to increase the power of the statistical tests.
      CONCLUSION: These results indicate the possibility that enhanced signal
      transduction, mediated by the 5-HT2A receptor, may be specific to bipolar
      disorder.

PMID- 11313100
TI  - Atherosclerosis and pancreatic damage.
AB  - The appearance of diabetes in advanced age may be considered as a part of the
      involutive processes of aging, and as such, it might have a pathogenesis
      completely different from that of type 2 diabetes of medium age. As a matter of
      fact, it has been observed that the pancreas undergoes numerous structural and
      functional alterations with advancing age, both in exocrine and endocrine parts.
      The present studies have been performed to reveal the quantity and quality of the
      pancreatic lesions, which may be attributed to atherosclerosis. We have already
      studied elderly subjects, therefore, we were now looking for further supports in
      a population of middle age people, died in complications of malignant
      hypertension. We investigated the pancreas, kidney and heart of 36 subjects (20
      males and 16 females) with mean age of 48.6+/-8.9 years. Of this group, eight
      subjects (22.2%) became diabetic after the appearance of malignant hypertension.
      Arteriolar atherosclerosis damage (hyalinosis, thickening and stenosis) of the
      pancreatic arterioles were found in 92.8% of the non-diabetic, and in 87.5% of
      the diabetic subjects. Lesions of the pancreatic islets were observed in 32% of
      the non-diabetics, and in 50% of the diabetic subjects. The pancreas is an organ,
      which tends particularly to develop atherosclerotic damage. The vascular lesion
      of atherosclerotic origin, independently from the mechanism of its appearance,
      causes first only a decrease of the blood flux and hypoxia in the pancreatic
      islets with a consecutive functional decline of the beta-cells. This is then
      followed by structural modifications of the islets accompanied by the appearance
      of hyalinosis, loss of beta-cells, and a further decrease of insulin production.

PMID- 11313101
TI  - Surrogate decision makers' attitudes towards tube feeding in the nursing home.
AB  - In the nursing home, a widely accepted medical practice is to recommend the
      initiation of long term tube feeding in residents with eating difficulties.
      However, frequently the nursing home resident has dementia, lacks decision-making
      capacity, and has no advance directives to guide the physician and the family
      member(s). Therefore, the family member or another surrogate decision maker has
      to make the difficult decision of whether or not to consent to the placement of a
      feeding tube. We surveyed 50 English speaking surrogates of nursing home
      residents who were on a feeding tube for at least 6 months. Each surrogate was
      contacted by telephone and was administered a 16-item structured questionnaire.
      Statistical analyses included frequency distributions, and the Wilcoxon signed
      rank test for two related samples. Most surrogates rated the residents' quality
      of life as poor or extremely poor. Yet, 78% of the surrogates perceived tube
      feeding to be beneficial, 62% would repeat their initial decision to initiate
      tube feeding, and 68% would not consider removal of the feeding tube. Their
      leading concerns were medical complications, tube feeding's impact on each
      resident's quality of life, and adequacy of nursing care. The surrogates were
      satisfied with their initial decision for the placement of a feeding tube despite
      their perception that there was no improvement in the quality of life of the
      residents. The surrogates may have viewed tube feeding as a life prolonging
      measure.

PMID- 11313102
TI  - Audit of percutaneous endoscopic gastrostomy (PEG): a questionnaire survey of
      hospital consultants.
AB  - One of the commonest indications for PEG is nutritional support in dysphagia. We
      investigated the current practice of PEG insertion in South Wales (UK). A postal
      questionnaire was sent to hospital consultants with responsibility for acute
      medical/geriatric intake in the South Wales area. Eighty-eight of 114 (78.5%)
      responded. In 69 of 107 (65%) responses (Radiologists and Geriatricians also
      performed PEG in some hospitals) Gastroenterologists performed the insertion of
      PEG. Seventy-one (87%) always involved speech therapists before PEG insertion.
      Forty-five (55%) and 47 (57%) always involved dieticians and nurses,
      respectively. Eighty (92%) involved carers before PEG. Sixty-three (76%) used
      nasogastric feed for nutritional support before PEG. Thirty-six of 80 (45%)
      responses would wait more than 2 weeks before inserting PEG (range less than 7
      days to more than 6 weeks). Five (6.5%) preferred long-term nasogastric feed to
      PEG. Twenty-five (30%) had definite knowledge of a PEG clinic in their hospital
      and 38 of 77 (49%) who responded to this question said there was no routine
      follow-up or were not aware about follow up of PEG patients. There is wide
      variation in the timing of PEG insertion and involvement of paramedical staff.
      More research needs to be undertaken to provide evidence so guidelines can be
      developed in this area. Follow up of patients with PEG is poor but current
      evidence suggests follow up of these patients may be worth while as some patients
      with dysphagic stroke can regain their swallow late.

PMID- 11313103
TI  - Comparison of the lateral diffusion coefficient of hepatocyte plasma membrane
      proteins in three strains of sensescence accelerated mouse (SAM).
AB  - The lateral diffusion coefficients of proteins (D(p)) were measured in hepatocyte
      plasma membrane in freshly prepared liver smears by means of the fluorescence
      recovery after photobleaching (FRAP) method. D(p) was measured after development
      of peroxide-induced autofluorescence (PIAF) in a total of 115 senescence
      accelerated mice (SAM), distributed in three strains, at least five age-groups in
      each, as follows: (i) SAMR1TA (25 males and 22 females), medium life span (MLS)
      in months, under specific pathogen free (SPF) conditions, MLS(spf) 20.1 and 20.0,
      respectively, while under conventional conditions, MLS(Deltapf)=18.9 in average
      for both sexes; (ii) SAMP6/Ta (18 males and 17 females), MLS(spf)=17.1 and 15.3,
      respectively, and MLS(cc)=8.1 for both sexes; (iii) SAMP6/Ta (17 males and 16
      females), MLS(spf)=15.6 and 14.7, respectively, and MLS(cc)=10.0 for both sexes.
      A highly significant negative linear age-correlation of D(p) (R=0.975 or higher)
      was found in each strain, being roughly proportional with the MLS(cc) values.
      Since the studied mice kept under SPF conditions survived longer, than under
      conventional conditions, the actual age-dependent decay rates of D(p) values did
      not differ significantly in two pairs of comparisons (female R1/P6 and female
      R1/P8), whereas they did in all other possible pairs, including also the normal
      C57BL/6 mice. The main conclusion can be drawn that the D(p) of hepatocyte
      membranes is a good biomarker of aging and survival also in SAM, as in all other
      inbred and outbred rodents, studied so far.

PMID- 11313104
TI  - A group of five parameters as a new biological marker on F344/N rats.
AB  - The National Institute for Longevity Sciences (NILS) established an aging farm
      (A/F) for producing aging/aged laboratory rodents at the Experimental Animal
      Facility Wing under the NILS A/F Guide planned by the Laboratory Animal Research
      Facilities (LARF). Five parameters, the average life span, the number of days of
      75, 50, and 25% survival points, and average of the top 10 longest life span
      among laboratory strains of rodents at NILS-A/F, were reproducible for F344/N
      rats specifically by strain and sex under the LARF A/F guide. These five
      parameters may serve as an effective and practical biological marker, especially
      in aging science including longevity science, to evaluate characteristics of
      strains of laboratory rodents. The five parameters can identify clear substrain
      differences between F344/N and F344/Du and breeder differences between F344/DuCrj
      and F344/DuCrl.

PMID- 11313105
TI  - Human-figure drawing and memory functioning across the adult life span.
AB  - The main objective was to evaluate changes in the ability to draw the human
      figure (HFD) across adult life span and to relate these changes to those known to
      exist in memory function. Healthy adults (1000) from each of 10 five-year cohorts
      between 35 and 80 years were recruited randomly from a population in northern
      Sweden. Each participant was administered a health examination including
      cognitive testing and a drawing test, and an extensive examination of memory
      functions. For the drawing variables HFDarch and HFDtot, there is a steady
      decrease in episodic memory with poor drawers performing at a lower level. For
      semantic memory up to 65 years of age, there is no difference in performance, but
      thereafter a decrease. Good drawers show a better memory performance than poor
      drawers. For priming data for both HFDarch and HFDtot, there seems to be an
      interaction between age and drawing, such that poor drawers perform at a lower
      level for the two oldest groups but not for the youngest group. The HFDess is a
      valuable instrument and can support clinical evaluation as a screening for
      cognitive decline. The reduction of essential body details was strongly related
      to dementia progression, and thus as good a predictor of cognitive decline as
      episodic memory performance. The reduced capacity to perform a complex HFD
      declines with age and is most pronounced in the oldest age groups.

PMID- 11313106
TI  - The effect of public long-term care insurance plan on care management and care
      planning in Japanese geriatric hospitals.
AB  - Japan, a society facing demographic aging at an incomparable speed, decided to
      introduce a new public long-term care insurance system to meet the expected need
      for elders to be cared for in the near future. The purpose of this study was to
      examine the change in knowledgeability on the side of managers of Japanese
      geriatric hospitals regarding (1) the concept of care-management as the
      methodology to supply care services to the elderly smoothly, and (2)
      comprehensive assessment for the elders as the technical skill in the process of
      materializing care management. Subjects were interviewed and questioned over the
      telephone according to a structural questionnaire. Managers (directors and office
      managers) of geriatric hospitals in 1996 and 1999. In 1996, the rate of
      knowledgeability for care management on the side of managers of geriatric
      hospitals was 70.0% (28/40) as a whole, increasing to 97.3% (71/73) in 1999. With
      regard to MDS-RAPs, the knowledgeability rate increased from 57.5% (23/40) in
      1996 to 95.9% (70/73) in 1999. However, regarding care planning, almost all of
      the hospitals that performed care planning were those in the category required to
      submit care plans to the municipal government. Geriatric hospitals that were not
      required to submit such plans did not perform such planning either in 1996 or in
      1999. It can be concluded that the decision to introduce a long-term care
      insurance system in Japan has led to a deeper understanding of the methodology of
      care management and a comprehensive assessment on the side of managers of
      geriatric hospitals.

PMID- 11313107
TI  - Risk assessment of the use of deltamethrin on bednets for the prevention of
      malaria.
AB  - Risk assessments covering the use of the pyrethroid, deltamethrin, on bednets for
      the prevention of malaria have been conducted The toxicity of deltamethrin in
      humans and animals is reviewed following both dermal and oral exposure. The no
      adverse-effect level (NOEL) for exposure via the dermal route was 1000 mg/kg body
      weight/day. From this an acceptable exposure level (AEL) of 10 mg/kg body
      weight/day has been derived. The NOEL for exposure via the oral route was 1 mg/kg
      body weight/day, with exposures above this causing neurotoxic effects in animals.
      This NOEL has been used to derive margins of safety compared with predicted
      exposures. While direct skin contact does not seem to cause systemic toxicity in
      humans, it can cause burning, numbness and tingling of the skin, which is a local
      effect. This too is taken into account in the risk assessments. The risk
      assessments cover those treating bednets, on an intermittent or regular basis,
      the washing of treated nets, sleeping under treated nets (infants, children and
      adults). Worst case scenarios for each of these situations show that dermal
      exposures are low (one-tenth or less of the AEL) and the margins of safety for
      systemic exposure derived from oral data are acceptable, ranging from 10 to 3300.
      The benefits of the use of treated bednets in reducing morbidity and mortality
      from malaria are considerable and it can be concluded that the risk:benefit ratio
      is very favourable.

PMID- 11313108
TI  - Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an
      epidemiologic study.
AB  - Animal studies have shown that dietary intake of benzo[a]pyrene (BaP), a
      polycyclic aromatic hydrocarbon (PAH), causes increased levels of tumors at
      several sites, particularly in the upper gastrointestinal tract. However, the
      role of dietary intake of BaP and cancer in humans is not clear. We created a BaP
      database of selected food products that could be linked to Food Frequency
      Questionnaires (FFQs) to estimate BaP intake. BaP levels were measured for each
      food line-item (composite samples) which consisted of a variety of foods in a
      FFQ. Composite sample parts were derived from the Second National Health and
      Nutrition Examination Survey (NHANES II) which represents the most common food
      items consumed by the general population. Meat samples were cooked by different
      techniques in controlled conditions, and by various restaurants and fast-food
      chains. Non-meat products were purchased from the major national supermarket
      chains. The quantities of BaP were measured using a thin-layer chromatography
      (TLC)/spectrofluorometer technique and were highly correlated with both BaP
      (r=0.99) [corrected] and sum of carcinogenic PAH (r=0.98) measured by HPLC
      technique. We linked our database to the results from a FFQ and estimated the
      daily BaP intake of various food items in 228 subjects in the Washington, DC
      metropolitan area. The highest levels of BaP (up to about 4 ng BaP/g of cooked
      meat) were found in grilled/barbecued very well done steaks and hamburgers and in
      grilled/barbecued well done chicken with skin. BaP concentrations were lower in
      meats that were grilled/barbecued to medium done and in all broiled or pan-fried
      meat samples regardless of doneness level. The BaP levels in non-meat items were
      generally low. However, certain cereals and greens (e.g. kale, collard greens)
      had levels up to 0.5 ng/g. In our population, the bread/cereal/grain, and
      grilled/barbecued meat, respectively, contributed 29 and 21 percent to the mean
      daily intake of BaP. This database may be helpful in initial attempts to assess
      dietary BaP exposures in studies of cancer etiology.

PMID- 11313109
TI  - Influence of prenylated and non-prenylated flavonoids on liver microsomal lipid
      peroxidation and oxidative injury in rat hepatocytes.
AB  - Prenylated chalcones from hops and beer were compared with non-prenylated
      flavonoids [chalconaringenin (CN), naringenin (NG), genistein (GS) and quercetin
      (QC)] for their ability to inhibit lipid peroxidation in rat liver microsomes.
      Chalcones with prenyl- or geranyl-groups (5 and 25 microM) were more effective
      inhibitors of microsomal lipid peroxidation than CN, NG or GS induced by
      Fe(2+)/ascorbate. Prenylated chalcones were effective inhibitors of microsomal
      lipid peroxidation induced by Fe(3+)-ADP/NADPH and by tert-butyl hydroperoxide
      (TBH) but to a lesser extent compared to the Fe(2+)/ascorbate system. An increase
      of prenyl substituents decreased antioxidant activity in the lipid peroxidation
      systems. Certain flavonoids behaved as prooxidants in the iron-dependent lipid
      peroxidation systems. For example, at 5 microM, NG enhanced iron/ascorbate
      induced lipid peroxidation whereas CN, diprenylxanthohumol and
      tetrahydroxanthohumol enhanced Fe(3+)-ADP/NADPH-induced lipid peroxidation. None
      of the flavonoids (25 microM), except QC, inhibited NADPH cytochrome P450
      reductase activity of rat liver microsomes, suggesting that the mechanism of
      inhibition of lipid peroxidation induced by Fe(3+)-ADP/NADPH is not due to
      inhibition of the reductase enzyme. Chalcones exhibiting antioxidant activity
      against TBH-induced lipid peroxidation such as xanthohumol and 5'
      prenylxanthohumol, and NG, with no antioxidant property at 5 microM concentration
      protected cultured rat hepatocytes from TBH toxicity. Other antioxidants
      (desmethylxanthohumol and CN) in the TBH system were not cytoprotective. These
      results demonstrate the importance of prenyl groups in the antioxidant activity
      of hop chalcones in the various in vitro systems of lipid peroxidation.
      Furthermore, the antioxidant activity of the flavonoids has little or no bearing
      on their ability to protect rat hepatocytes from the toxic effects of TBH.

PMID- 11313110
TI  - Reproductive and neurobehavioural toxicity study of erythrosine administered to
      mice in the diet.
AB  - Erythrosine was given in the diet to provide levels of 0 (control), 0.005, 0.015
      and 0.045% from 5 weeks of age of the F(0) generation to 9 weeks of age of the
      F(1) generation in mice, and selected reproductive and neurobehavioural
      parameters were measured. There were no adverse effects of erythrosine on either
      litter size, litter weight or sex ratio at birth. The average body weight of the
      offspring was significantly increased in the middle-dose group in both sexes
      during the lactation period. In behavioural developmental parameters, any
      variables showed no significant adverse effects in either sex in the lactation
      period. In movement activity of exploratory behaviour, several parameters were
      significantly changed in the high-dose group, and those effects were dose related
      in adult females in the F(0) and F(1) generations and in male offspring in the
      F(1) generation. The dose level of erythrosine in the present study produced few
      adverse effects in reproductive and neurobehavioural parameters in mice.

PMID- 11313111
TI  - The effect of a single gavage dose of fumonisin B(2) on the sphinganine and
      sphingosine concentrations in vervet monkeys.
AB  - The disruption in sphinganine (Sa) and sphingosine (So) concentrations in plasma
      and urine of vervet monkeys (Cercopithecus aethiops) was measured following a
      single gavage dose of either 1 (low dose) or 10 mg (high dose) fumonisin B(2)
      (FB(2))/kg body weight. Blood and urine were collected over a 51-day period. In
      the low-dose monkeys, none of the parameters measured increased significantly
      above the control values. In the high-dose monkeys the plasma Sa/So ratios were
      significantly increased (P< 0.05) above the corresponding control ratios after 3
      days and continued to be significantly raised for another 27 days, whereafter the
      ratios declined to control values after 51 days. The plasma aspartate
      transaminase (AST) activities increased significantly above their control values
      from day 5 to day 23 and the gamma-glutamyl transferase (GGT) activities from day
      7 until the end of the study period. The plasma cholesterol concentration and
      alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities increased
      transiently, but not significantly, and returned to control values within the
      study period. The urinary Sa/So ratio, plasma creatinine and urea values in both
      groups of monkeys did not increase above the control values. This study
      demonstrated that a single large dose of FB(2) can cause transient disruption of
      sphingoid metabolism in vervet monkeys.

PMID- 11313112
TI  - Production, purification, and characterization of an intracellular aflatoxin
      detoxifizyme from Armillariella tabescens (E-20).
AB  - Some Armillariella tabescens (E-20) multienzymes have previously been reported to
      present detoxifying activities against aflatoxins. In this paper, we describe the
      isolation purification of an intracellular enzyme, named aflatoxin-detoxifizyme,
      which exhibited detoxification activity on aflatoxin B(1) (AFB(1)). This
      aflatoxin-detoxifizyme exhibited a specific activity of 7.09 nmol min/mg at pH
      6.0 and 28 degrees C. The apparent molecular mass was 51.8 kDa as determined by
      SDS-PAGE. The isoelectric point was estimated to be 5.4 and optimum activity for
      the enzyme was found at pH 6.8 and 35 degrees C. The activity of the purified
      enzyme was confirmed by Ames test.

PMID- 11313113
TI  - Toxicological consequences of toxaphene ingestion by cynomolgus (Macaca
      fascicularis) monkeys. Part 1: pre-mating phase.
AB  - A total of 40 menstruating cynomolgus monkeys (Macaca fascicularis) with an
      average age of 7.25 +/- 1.06 years (standard deviation), five male cynomolgus
      monkeys with an average age of 12.6 +/- 0.66 years, and five male cynomolgus
      males with an average age of 6.2 +/- 0.23 years were obtained from the Health
      Canada breeding laboratory. The females were initially randomized to the four
      test groups in accordance with their previous reproductive success and body
      weight. They were then randomly allocated between two similar environmentally
      controlled rooms (20 females/room). The males were randomly assigned to one of
      the test rooms (six or four males/room). The female test groups self-ingested
      capsules containing doses of 0, 0.1, 0.4 or 0.8 mg (Groups A, B, C, D) of
      technical grade toxaphene/kg body weight/day (i.e. five females/dose group/room).
      The older males (Group E) were proven breeders and were used exclusively for
      mating and their capsules contained no toxaphene. The younger males (Group F)
      ingested capsules containing 0.8 mg of technical grade toxaphene/kg body
      weight/day. After 20 weeks of daily dosing, it was assumed, based on the results
      of a pilot study [Andrews P., Headrick K., Pilon J.-C., Bryce F., Iverson F.
      (1996) Capillary GC-ECD and ECNI GCMS characterization of toxaphene residues in
      primate tissues during a feed study. Chemosphere 32, 1043-1053], that the treated
      monkeys had attained a qualitative pharmacokinetic steady state regarding the
      concentration of toxaphene in their adipose tissue and blood. On a daily basis,
      each monkey's feed and water consumption as well as its health were monitored. In
      addition, the females were swabbed daily to determine menstrual status. On a
      weekly basis, each monkey's body weight was determined and its dose of toxaphene
      adjusted. Detailed clinical examinations were conducted at intervals of 4 weeks
      or less. Periodically, starting prior to the initiation of dosing, blood samples
      were taken for serum biochemistry, haematology and toxaphene analysis. In
      addition, specimens from the nuchal fat pad were also obtained for toxaphene
      analysis. Statistical analysis did not reveal any effect of treatment on body
      weight gain, feed consumption, water consumption or haematological parameters
      during the 75-week pre-mating phase. The only serum biochemistry parameter which
      was consistently affected by treatment was cholesterol, the level of which
      decreased in a linear fashion as a consequence of dose, and this effect increased
      with time on test (P = 0.037). No other biological effects of toxaphene ingestion
      were found during the premating phase of this toxicological-reproduction study.

PMID- 11313114
TI  - Azadirachtin, a neem biopesticide: subchronic toxicity assessment in rats.
AB  - Azadirachtin, a biopesticide obtained from neem, was subjected to subchronic
      toxicological testing to document its safety for use as a pesticide. Azadirachtin
      technical 12% orally administered to male and female rats at doses of 500, 1000
      and 1500 mg/kg/day for 90 days did not produce any signs of toxicity, mortality,
      changes in tissue weight, pathology and serum and blood parameters. It can be
      suggested that azadirachtin at the highest dose tested is well tolerated by rats
      of both sexes. The highest dose, 1500 mg/kg, can be used as a basal dose for the
      determination of the no-observed-effect level (NOEL) of azadirachtin to calculate
      its safety margin.

PMID- 11313115
TI  - Genotoxicity of dill (Anethum graveolens L.), peppermint (Menthaxpiperita L.) and
      pine (Pinus sylvestris L.) essential oils in human lymphocytes and Drosophila
      melanogaster.
AB  - Genotoxic properties of the essential oils extracted from dill (Anethum
      graveolens L.) herb and seeds, peppermint (Menthaxpiperita L.) herb and pine
      (Pinus sylvestris L.) needles were studied using chromosome aberration (CA) and
      sister chromatid exchange (SCE) tests in human lymphocytes in vitro, and
      Drosophila melanogaster somatic mutation and recombination test (SMART) in vivo.
      In the CA test, the most active essential oil was from dill seeds, then followed
      essential oils from dill herb, peppermint herb and pine needles, respectively. In
      the SCE test, the most active essential oils were from dill herb and seeds
      followed by essential oils from pine needles and peppermint herb. Essential oils
      from dill herb and seeds and pine needles induced CA and SCE in a clear dose
      dependent manner, while peppermint essential oil induced SCE in a dose
      independent manner. All essential oils were cytotoxic for human lymphocytes. In
      the SMART test, a dose-dependent increase in mutation frequency was observed for
      essential oils from pine and dill herb. Peppermint essential oil induced
      mutations in a dose-independent manner. Essential oil from dill seeds was almost
      inactive in the SMART test.

PMID- 11313116
TI  - Anti-genotoxicity of trans-anethole and eugenol in mice.
AB  - The naturally occurring flavouring agents trans-anethole and eugenol were
      evaluated for antigenotoxic effects in mice. The test doses of trans-anethole (40
      400 mg/kg body weight) and eugenol (50-500 mg/kg weight) were administered by
      gavage 2 and 20 h before the genotoxins were injected intraperitoneally. Anti
      genotoxic effects were assessed in the mouse bone marrow micronucleus test.
      Pretreatment with trans-anethole and eugenol led to significant antigenotoxic
      effects against cyclophosphamide (CPH), procarbazine (PCB), N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) and urethane (URE). In addition, trans-anethole inhibited
      the genotoxicity of ethyl methane sulfonate (EMS). Both trans-anethole and
      eugenol exerted dose-related antigenotoxic effects against PCB and URE. There was
      no significant increase in genotoxicity when trans-anethole (40-400 mg/kg body
      weight) and eugenol (50-500 mg/kg body weight) were administered alone.

PMID- 11313117
TI  - Effect of pyrolysis temperature on the mutagenicity of tobacco smoke condensate.
AB  - Tobacco smoke aerosols with fewer mutagens in the particulate fraction may
      present reduced risk to the smoker. The objective of this study was to test the
      hypothesis that the temperature at which tobacco is pyrolyzed or combusted can
      affect the mutagenicity of the particulate fraction of the smoke aerosol. Tobacco
      smoke aerosol was generated under precisely controlled temperature conditions
      from 250 to 550 degrees C by heating compressed tobacco tablets in air. The
      tobacco aerosols generated had a cigarette smoke-like appearance and aroma. The
      tobacco smoke aerosol was passed through a Cambridge filter pad to collect the
      particulate fraction, termed the smoke condensate. Although condensates of
      tobacco smoke and whole cigarette mainstream smoke share many of the same
      chemical components, there are physical and chemical differences between the two
      complex mixtures. The condensates from smoke aerosols prepared at different
      temperatures were assayed in the Ames Salmonella microsome test with metabolic
      activation by rat liver S9 using tester strains TA98 and TA100. Tobacco smoke
      condensates were not detectably mutagenic in strain TA98 when the tobacco smoke
      aerosol was generated at temperatures below 400 degrees C. Above 400 degrees C,
      condensates were mutagenic in strain TA98. Similarly, condensates prepared from
      tobacco smoke aerosols generated at temperatures below 475 degrees C were not
      detectably mutagenic in strain TA100. In contrast, tobacco tablets heated to
      temperatures of 475 degrees C or greater generated smoke aerosol that was
      detectably mutagenic as measured in TA100. Therefore, heating and pyrolyzing
      tobacco at temperatures below those found in tobacco burning cigarettes reduces
      the mutagenicity of the smoke condensate. Highly mutagenic heterocyclic amines
      derived from the pyrolysis of tobacco leaf protein may be important contributors
      to the high temperature production of tobacco smoke Ames Salmonella mutagens. The
      relevance of these findings regarding cancer risk in humans is difficult to
      assess because of the lack of a direct correlation between mutagenicity in the
      Ames Salmonella test and carcinogenicity.

PMID- 11313118
TI  - Ineffectiveness of activated carbon in reducing the alteration of sphingolipid
      metabolism in rats exposed to fumonisin-contaminated diets.
AB  - Sphinganine/sphingosine (SA/SO) ratio, a biomarker of fumonisin exposure, has
      been measured in urine, kidney and liver of male Wistar rats exposed to fumonisin
      contaminated diet with and without the addition of activated carbon (AC). The
      latter was previously shown to adsorb fumonisin B(1) in vitro. Rats were fed
      either control diet or fumonisin-contaminated diet (4 microg FB(1+)FB(2)/g) or
      fumonisin-contaminated diet mixed with 20 mg AC/g diet for 1 week. In rats fed
      fumonisin-contaminated diet, the SA concentration and SA/SO ratio increased
      significantly and reversibly in kidney, while urine and liver did not show a
      significant increase of SA/SO ratio. The addition of AC to the fumonisin
      contaminated diet did not alter the change of SA/SO biomarker for fumonisin
      exposure. This provides indications that the use of AC to reduce the toxicity of
      fumonisins is unlikely to be effective in vivo.

PMID- 11313125
TI  - Glycosylphosphatidylinositol-anchored receptor-mediated bacterial endocytosis.
AB  - An increasing number of pathogens or their toxins appear to utilize
      glycosylphosphatidylinositol(GPI)-anchored receptors to trigger entry into immune
      and other host cells. Since these receptors have no transmembrane and
      intracellular moieties, how endocytosis is initiated is unclear. Recently, CD48
      on mast cell membranes was shown to trigger endocytosis of bacteria via a route
      that avoids fusion with lysosomes and by a mechanism involving discrete cellular
      entities called caveolae. The localization of CD48 within caveolae appears to be
      a prerequisite for caveolae-mediated bacterial entry.

PMID- 11313126
TI  - Use of repetitive DNA elements to define genetic relationships among Anaplasma
      marginale isolates.
AB  - Anaplasma marginale genomic DNA was tested for the presence of repetitive
      extragenic palindromic (REP) and enterobacterial repetitive intergenic consensus
      (ERIC)-like sequences in order to evaluate the genetic diversity of multiple A.
      marginale isolates. A. marginale isolates were obtained from cattle of six
      different states of Brazil, from the US and an Anaplasma centrale strain was
      obtained from Uruguay. Patterns obtained from A. marginale isolates varied from
      14 to 17 fragments by REP-polymerase chain reaction (PCR) and 6 to 14 fragments
      by ERIC-PCR. All A. marginale isolates presented a 0.75-kb fragment by REP and
      two common fragments (0.38 and 1.0 kb) by ERIC-PCR. These two fragments were not
      detectable in A. centrale. Both methods produced similar patterns (80%) among A.
      marginale isolates obtained from the same region, although some isolates within
      regions shared less similarity. Isolates from Parana and Pernambuco, were
      differentiated by these methods. The study demonstrates the presence of ERIC and
      REP-like elements in A. marginale isolates and shows that A. marginale isolates
      and strains can be differentiated by these methods.

PMID- 11313127
TI  - Analysis of proteins in the extracellular matrix of the plant pathogenic fungus
      Bipolaris sorokiniana using 2-D gel electrophoresis and MS/MS.
AB  - A method was developed for isolating and sequencing proteins present in the
      extracellular matrix (ECM) of germlings and hyphae of filamentous fungi. Surface
      proteins of the cereal pathogen Bipolaris sorokiniana were labelled with a
      membrane impermeable biotinylating agent and extracted using a glycine-HCl
      buffer. Extracted proteins were purified by affinity binding to streptavidin
      conjugated magnetic beads or by two-dimensional gel electrophoresis. Four of the
      biotinylated proteins from the ECM of B. sorokiniana were isolated, in gel
      digested with trypsin and partly sequenced by tandem mass spectrometry. No
      significant sequence similarities to proteins in databases were obtained.

PMID- 11313128
TI  - Characterization and expression of secA in Mycobacterium avium.
AB  - Mycobacterium avium is both a pathogen that infects several hosts such as humans,
      pigs, and birds, as well as a microorganism that is encountered in environmental
      sources (soil and water). Protein secretion by the bacterium is likely to
      influence its ability to overcome adverse and competitive conditions both within
      or outside the host. Using a combination of cloning and information available in
      the databank, we characterized the secA gene from M. avium, encoding for a major
      preprotein translocase subunit associated with the secretion system of
      prokaryotics. In addition, we cloned the secA promoter sequence in a reporter
      construct upstream of a promoterless gfp. It was determined that the secA of M.
      avium shares large homology with the secA of Mycobacterium tuberculosis but not
      with secA of Mycobacterium leprae. secA expression was determined to be greater
      at logarithmic growth phase although it was also expressed at low levels during
      the stationary phase. secA expression was also observed when the bacteria were
      incubated in water as well as within human monocyte-derived macrophages and in
      conditions that are associated with biofilm formation. Future evaluation of the
      sec pathway in M. avium might provide important information about secreted
      proteins that are required for survival in different environments.

PMID- 11313129
TI  - Construction of a modified mini-Tn5 luxCDABE transposon for the development of
      bacterial biosensors for ecotoxicity testing.
AB  - A mini-Tn5 transposon was modified to introduce a promoterless luxCDABE cassette
      from Vibrio fischeri into environmentally relevant bacterial strains in order to
      develop bioluminescence-based biosensors for toxicity testing. The mini-Tn5
      luxCDABE transposon was chromosomally integrated downstream from an active
      promoter into two Pseudomonas strains (Pseudomonas fluorescens 8866 and
      Pseudomonas putida F1). Characterisation of the bioluminescent transconjugants
      demonstrated that the transposon integration was stable and had no effect on
      growth rate. Both P. fluorescens 8866 Tn5 luxCDABE and P. putida F1 Tn5 luxCDABE
      were used to assess the toxicity of standard solutions (Cu, Zn and 3,5-DCP) as
      well as Cu- and 3,5-DCP-spiked groundwater samples. They were successfully used
      for bioluminescence-based bioassays and the potential value of using different
      bacterial biosensors for ecotoxicity testing was shown.

PMID- 11313130
TI  - PCR detection of Brachyspira aalborgi and Brachyspira pilosicoli in human faeces.
AB  - Previously-developed PCR protocols specific for the 16S rRNA gene of the
      intestinal spirochaetes Brachyspira aalborgi and Brachyspira pilosicoli were
      adapted for the detection of these species in human faeces, following DNA
      extraction and purification using mini-prep columns. The limits of detection in
      seeded faeces for B. aalborgi and B. pilosicoli respectively were 2x10(2) and
      7x10(3) cells per PCR reaction, equivalent to 5x10(4) and 1x10(5) cells per g of
      faeces. The PCR techniques were applied to faecal samples from two patients with
      histological evidence of intestinal spirochaetosis. In the first patient, in whom
      B. aalborgi had been identified by 16S rDNA PCR from colonic biopsies, a positive
      amplification for B. aalborgi only was obtained from the faeces. The organism
      could not be isolated from these faeces. In the second patient, both colonic
      biopsies and faeces were PCR positive for B. pilosicoli only, and B. pilosicoli
      was isolated from the faeces. These new faecal PCR protocols should be valuable
      for future studies on the epidemiology of intestinal spirochaete infections in
      human populations, particularly as it is not currently possible to isolate B.
      aalborgi from faeces.

PMID- 11313131
TI  - Phylogeny and distribution of the soxB gene among thiosulfate-oxidizing bacteria.
AB  - A PCR protocol for the detection of sulfur-oxidizing bacteria based on soxB genes
      that are essential for thiosulfate oxidation by sulfur-oxidizing bacteria of
      various phylogenetic groups which use the 'Paracoccus sulfur oxidation' pathway
      was developed. Five degenerate primers were used to specifically amplify
      fragments of soxB genes from different sulfur-oxidizing bacteria previously shown
      to oxidize thiosulfate. The PCR yielded a soxB fragment of approximately 1000 bp
      from most of the bacteria. Amino acid and nucleotide sequences of soxB from
      reference strains as well as from new isolates and environmental DNA from a
      hydrothermal vent habitat in the North Fiji Basin were compared and used to infer
      relationships of soxB between sulfur-oxidizing bacteria belonging to various 16S
      rDNA-based phylogenetic groups. Major phylogenetic lines derived from 16S rDNA
      were confirmed by soxB phylogeny. Thiosulfate-oxidizing green sulfur bacteria
      formed a coherent group by their soxB sequences. Likewise, clearly separated
      branches demonstrated the distant relationship of representatives of alpha-, beta
      , and gamma-Proteobacteria including representative species of the former genus
      Thiobacillus (now Halothiobacillus - gamma-Proteobacteria, Thiobacillus - beta
      Proteobacteria and Starkeya - alpha-Proteobacteria). This general picture emerged
      although apparent evidence for lateral transfer of the soxB gene is indicated and
      comparison of soxB phylogeny and 16S rDNA phylogeny points to the significance of
      this gene transfer in hydrothermal vent bacterial communities of the North Fiji
      Basin.

PMID- 11313132
TI  - FTIR spectroscopic analysis of Saccharomyces cerevisiae cell walls: study of an
      anomalous strain exhibiting a pink-colored cell phenotype.
AB  - A new strain, exhibiting an intriguing pink-colored cell phenotype, was obtained
      after an encoding alpha-glucosidase gene from an archaebacteria Thermococcus
      hydrothermalis was cloned by functional complementation of a mal11 Saccharomyces
      cerevisiae mutant TCY70. The possible implications of the alpha-glucosidase on
      the cell wall were evaluated by infrared spectroscopy and data indicate a 30%
      decrease in mannoproteins and an increase in beta-glucans. The loss of
      mannoproteins was confirmed by experiments on cells deprived of peptidomannans.
      Modifications in the major components of the cell wall did not jeopardize cell
      viability. Such rapid optical spectroscopic method can be used to screen a wide
      range of yeast mutants.

PMID- 11313133
TI  - Outer sheath associated proteins of the oral spirochete Treponema maltophilum.
AB  - We recently cloned the major outer membrane protein of Treponema maltophilum
      [Heuner, K., Choi, B.K., Schade, R., Moter, A., Otto, A., Gobel, U.B., J.
      Bacteriol. 181, 1025-1029]. Here we report the localization of the major sheath
      protein (Msp)A protein in T. maltophilum by immunogold electron microscopy and
      its expression. Northern blot analysis revealed that mspA is expressed
      constitutively as a monocistronic unit. The transcription initiation site of the
      mspA gene was identified by primer extension analysis. A further screening of a
      genomic library of T. maltophilum with an anti-outer membrane fraction antibody
      was done. We were able to clone DNA regions of T. maltophilum encoding putative
      sugar transport operons and putative outer membrane proteins of this oral
      treponeme which has a high prevalence in periodontal lesions.

PMID- 11313134
TI  - Use of representational difference analysis to identify Escherichia coli O157
      specific DNA sequences.
AB  - Whereas several important virulence factors in Escherichia coli O157 have been
      identified, studies suggest they are not always essential and are probably
      insufficient to account for the severe clinical manifestation of E. coli O157
      infection. Identification of putative virulence determinants is crucial to the
      understanding of bacterial pathogenesis and genomic comparison analysis may aid
      the characterisation of unidentified virulence attributes. In this study,
      representational difference analysis (RDA) was used for genomic comparison of E.
      coli O157 with the proposed ancestral strain, E. coli O55. Unique E. coli O157
      gene sequences were isolated and one, termed RDA-1, taken forward for further
      analysis. Southern blotting with labelled RDA-1 as a probe showed it to be
      present in 77% of E. coli O157 isolates and absent in all non-E. coli O157
      screened. Sequence flanking RDA-1 was obtained from a genomic clone identified by
      hybridisation, and contained an open reading frame predicted to encode a novel
      iron-regulated outer membrane protein.

PMID- 11313135
TI  - Characterization of the mutS-proximal region of the Salmonella typhimurium SPI-1
      identifies a group of pathogenicity island-associated genes.
AB  - The virulence properties of Salmonella enterica are largely encoded within a set
      of horizontally acquired gene blocks termed pathogenicity islands. One such
      pathogenicity island, SPI-1, located at centisome 63 of the Salmonella chromosome
      between the mutS and fhlA genes, encodes a type III protein secretion system and
      an iron uptake system. We have characterized the mutS-proximal border of this
      pathogenicity island and have identified two sets of genes, pigAB and pigCD. All
      four genes have homologs of unknown function in several bacteria that share the
      ability to establish an intimate association with higher eukaryotic hosts. The
      expression of at least two of these genes, pigA and pigB, is controlled by SprA,
      a transcription factor encoded within SPI-1 that controls the expression of genes
      associated with the type III secretion system of this island. In addition, we
      found that homologs of the pig genes are also found at different locations of the
      S. enterica chromosome in association with segments of DNA that exhibit features
      of pathogenicity islands. The presence of several apparently functional copies of
      these genes argues for an important role in the biology of this bacterial
      pathogen. Furthermore, they constitute a valuable tool to identify potential
      pathogenicity islands.

PMID- 11313136
TI  - A novel actin-related protein gene of Colletotrichum gloeosporioides f. sp.
      malvae shows altered expression corresponding with spore production.
AB  - A novel actin-related protein (arp) was found in the plant pathogenic fungus,
      Colletotrichum gloeosporioides f. sp. malvae (Cgm), which causes anthracnose
      disease of round-leaved mallow (Malva pusilla). Sequence comparisons showed that
      this gene, arpA, belongs to the highly divergent 'other arps' category in the
      current arp classification system. ArpA is most similar to the arp11 gene of Mus
      musculus but has a unique structure with deletions at the C-terminus similar to
      that of the arp10 gene of Saccharomyces cerevisiae. A portion of another putative
      arp gene, arpB, was found immediately downstream of arpA. Expression of arpA was
      compared to the constitutively expressed Cgm actin gene, actA. In culture, the
      relative expression of arpA increased when growth conditions favored sporulation.
      During infection, arpA expression was greatest at the late necrotrophic phase,
      when sporulation occurred. Arps have been shown to be important in nuclear
      migration in fungal hyphae, and the expression pattern of arpA indicates that it
      may have a particular role during sporulation.

PMID- 11313137
TI  - TRAM, a predicted RNA-binding domain, common to tRNA uracil methylation and
      adenine thiolation enzymes.
AB  - A previously undetected conserved domain is identified in two distinct classes of
      tRNA-modifying enzymes, namely uridine methylases of the TRM2 family and enzymes
      of the MiaB family that are involved in 2-methylthioadenine formation. This
      domain, for which the acronym TRAM is proposed after TRM2 and MiaB, is predicted
      to bind tRNA and deliver the RNA-modifying enzymatic domains to their targets. In
      addition to the two families of RNA-modifying enzymes, the TRAM domain is present
      in several other proteins associated with the translation machinery and in a
      family of small, uncharacterized archaeal proteins that are predicted to have a
      role in the regulation of tRNA modification or translation. Secondary structure
      prediction indicates that the TRAM domain adopts a simple beta-barrel fold. In
      addition, sequence analysis of the MiaB family enzymes showed that they share the
      predicted catalytic site with biotin and lipoate synthases and probably employ
      the same mechanism for sulfur insertion into their respective substrate.

PMID- 11313138
TI  - Psychrotolerant species from the Bacillus cereus group are not necessarily
      Bacillus weihenstephanensis.
AB  - Twenty-six strains of Bacillus cereus from different sources were determined to
      be either mesophilic or psychrotrophic by growth at 6 and 42 degrees C. The
      strains were also screened by two polymerase chain reaction (PCR) methods
      designed to discriminate between mesophilic and psychrotrophic types. Seventeen
      of the 26 strains were able to grow at 6 degrees C, but only four conformed to
      the new psychrotolerant species Bacillus weihenstephanensis. Among the 26 strains
      were two which caused outbreaks of food poisoning in Norway, and three others
      that were isolated from food suspected of causing illness. The presence of the
      gene components encoding production of enterotoxins Nhe, Hbl, EntT and a recently
      described cytotoxin K was determined by PCR. All the strains possessed genes for
      at least one of these toxins, and 19 of the 26 strains were cytotoxic in a Vero
      cell assay. We conclude that there are psychrotrophic B. cereus strains which
      cannot be classified as B. weihenstephanensis, and that intermediate forms
      between the two species exist. No correlation between cytotoxicity and the growth
      temperature of the strains was found.

PMID- 11313139
TI  - The failure of different strains of Yersinia pestis to produce lipopolysaccharide
      O-antigen under different growth conditions is due to mutations in the O-antigen
      gene cluster.
AB  - The lipopolysaccharide (LPS) from eight strains of Yersinia pestis which had been
      cultured at 28 degrees C appeared to be devoid of an O-antigen when analysed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. LPS isolated from
      three of these strains which had been cultured at 37 degrees C also appeared to
      be devoid of an O-antigen. When the LPS from Y. pestis strain CO92 was purified
      and analysed by matrix-assisted laser desorption-ionisation time-of-flight mass
      spectrometry, the observed signals were in the mass range predicted for molecules
      containing lipid A plus the core oligosaccharide but lacking an O-antigen. The
      nucleotide sequence of Y. pestis strain CO92 revealed the presence of a putative
      O-antigen gene cluster. However, frame-shift mutations in the ddhB, gmd, fcl and
      ushA genes are likely to prevent expression of the O-antigen thus explaining the
      loss of phenotype.

PMID- 11313140
TI  - Corynebacterium diphtheriae surface proteins as adhesins to human erythrocytes.
AB  - Corynebacterium diphtheriae strains express non-fimbrial surface proteins able to
      recognize and bind to specific host cells receptors. Protein extracts were
      obtained from bacterial cells by mechanical process and ammonium sulfate
      precipitation at 25 and 45% (w/v) saturation. SDS-PAGE analysis of the extracts
      detected two polypeptide bands of 67 and 72 kDa, named 67-72 p. The 67-72 p,
      rabbit anti-67-72 p IgG antibodies as well as human gastric mucin, N
      acetylneuraminic acid and N-acetyl D-glucosamine molecules were able to inhibit
      bacterial hemagglutination. Hemagglutination assays using 67-72 p-coated latex
      beads and Western blot analysis of biotin-labeled 67-72 p and erythrocyte
      receptors demonstrated the binding of 67-72 p to human erythrocyte membranes.
      Immunolabeled colloidal gold-A protein transmission electron microscopy using
      anti-67-72 p revealed a diffuse distribution of non-fimbrial 67-72 p on the
      surface of C. diphtheriae strains of both sucrose-fermenting and non-fermenting
      biotypes. Non-fimbrial lectin-like surface 67-72 p may play a role as adhesins in
      bacterial attachment thereby facilitating the early steps in pathogenesis of both
      toxigenic and non-toxigenic C. diphtheriae.

PMID- 11313141
TI  - Molecular analysis of genetic differences among inbred mouse strains controlling
      tissue expression pattern of alcohol dehydrogenase 4.
AB  - The ADH gene family in vertebrates is composed of at least seven distinct classes
      based upon sequence comparisons and enzyme properties. The Adh4 gene product may
      play an important role in differentiation and development because of its capacity
      to metabolize retinol to retinoic acid. Allelic gene differences exist among
      inbred mouse strains which control structure and tissue-specific regulation of
      Adh4. C57BL/6 mice are unique and have no detectable ADH4 enzyme activity in
      epididymis and low levels in seminal vesicle, ovary and uterus compared to other
      strains. C57BL/6 mice express Adh4 in stomach at levels similar to other strains.
      The goal of this research was to investigate this genetic variation at the
      molecular level. Northern analysis revealed that the content of ADH4 mRNA in
      tissues correlate with the enzyme expression pattern. Interestingly, C57BL/6 mice
      express an ADH4 mRNA in stomach which is smaller than expressed in C3H and other
      mice. An analysis of the 5'- and 3'-ends of the mRNA using RACE analysis
      determined that the ADH4 mRNA in C57BL/6 mice is truncated in the 3'-untranslated
      region. Sequence analysis of RACE products showed that the truncation is due to a
      single nucleotide mutation which produces an early polyadenylation signal.
      Additional RACE and Northern analysis revealed that at least five different
      polyadenylation sites are used in the Adh4 gene. Using 3'-end polymorphisms found
      between C57BL/6 and C3H strains and RT-PCR, it was shown that the lack of
      expression in epididymis in C57BL/6 mice is cis-acting in F(1) hybrid animals.
      The DNA sequence of the proximal promoter (-600/+42 nt) was determined in several
      mouse strains differing in tissue-specific expression patterns and did not reveal
      any nucleotide substitutions correlating with expression pattern suggesting
      further upstream or downstream sequences may be involved.

PMID- 11313142
TI  - Natural antisense transcripts are detected in different cell lines and tissues of
      cats infected with feline immunodeficiency virus.
AB  - Feline immunodeficiency virus (FIV) is a lentivirus inducing an AIDS-like disease
      in cats, thus providing an interesting model for AIDS study. FIV and HIV-1
      possess a similar genomic arrangement of structural and non-structural genes,
      whose expression is regulated by related genetic mechanisms. On the DNA strand
      complementary to the HIV-1 envelope messenger, an open reading frame (ORF) has
      been identified which encompasses the Rev Responsive Element (RRE), a cis-acting
      element critical to HIV gene expression. This ORF was highly conserved among HIV
      1 isolates and had the potential to encode a hydrophobic protein. A corresponding
      antisense transcript was detected in cells infected with HIV-1, and appeared to
      encode an antisense protein. In the present study, we have identified a well
      conserved antisense ORF, also coincident with the RRE region, in the genome of 21
      FIV isolates. The predicted protein, 103 amino acids in length, is highly
      hydrophobic, as is the case for that of HIV-1. In addition, we have shown that a
      corresponding transcript, complementary to the transmembrane sequence of the FIV
      envelope gene, was produced in different cellular and viral contexts, that is, ex
      vivo and in vivo in FIV infected cell lines and tissues of infected cats,
      respectively. Expression of antisense transcripts might therefore be of general
      importance in the natural history of retroviruses.

PMID- 11313143
TI  - Identification and cellular localization of human PFTAIRE1.
AB  - We isolated a novel member of putative Cdc2-related serine/threonine protein
      kinases from a Hela cell cDNA library. The cDNA encodes a protein of 469 amino
      acids, sharing 95% identities with the mouse PFTAIRE1 throughout the entire
      protein sequence. This gene was designated human PFTAIRE1. The gene was located
      at human chromosome 7q21.13 with radiation hybrid polyermase chain reaction (RH
      PCR) analysis. By Northern blotting analysis, an approximately 6 kb transcript is
      detected with varied levels of expression of the hPFTAIRE1 in 16 human tissues.
      The hPFTAIRE1 was highly expressed in brain, pancreas, kidney, heart, testis and
      ovary. The transcript was also detected at lower level in other tissues, except
      in spleen and thymus where the transcript was hardly detected. The protein was
      fused to the C-terminus of a green fluorescent protein (GFP) and ectopically
      expressed in Hela cells. The florescence microscope results indicated that the
      hPFTAIRE1 exhibits cytoplasmic distribution.

PMID- 11313144
TI  - MAGE-F1, a novel ubiquitously expressed member of the MAGE superfamily.
AB  - Most known members of the MAGE superfamily are expressed in tumors, testis and
      fetal tissues, which has been described as a cancer/testis or "CT" expression
      pattern. We have identified a novel member of this superfamily, MAGE-F1, which is
      expressed in all adult and fetal tissues tested. In addition to normal tissues,
      MAGE-F1 is expressed in many tumor types including ovarian, breast, cervical,
      melanoma and leukemia. MAGE-F1 is encoded on chromosome 3, identifying a sixth
      chromosomal location for a MAGE superfamily gene. The coding region of MAGE-F1 is
      contained within a single exon and includes a microsatellite repeat. Sequence
      analysis and expression profiles define a new class of ubiquitously expressed
      MAGE superfamily genes that includes MAGE-F1, MAGE-D1, MAGE-D2/JCL-1 and NDN. The
      finding that several MAGE genes are ubiquitously expressed suggests a role for
      MAGE encoded proteins in normal cell physiology. Furthermore, potential cross
      reactivity to these ubiquitously expressed MAGE gene products should be
      considered in the design of MAGE-targeted immunotherapies for cancer.

PMID- 11313145
TI  - Identification of a PD-(D/E)XK-like domain with a novel configuration of the
      endonuclease active site in the methyl-directed restriction enzyme Mrr and its
      homologs.
AB  - The Escherichia coli K-12 restriction enzyme Mrr recognizes and cleaves N6
      methyladenine- and 5-methylcytosine-containing DNA. Its amino acid sequence has
      been subjected to structure prediction and comparison with other sequences from
      publicly available sources. The results obtained suggest that Mrr and related
      putative endonucleases possess a cleavage domain typical for all the so far
      structurally characterized type II restriction enzymes, however with an unusual
      glutamine residue at the central position of the (D/E)-(D/E)XK hallmark of the
      active site. The "missing" acidic side chain was instead found anchored in a
      different, unusual position, suggesting that Mrr represents a third topological
      variant of the endonuclease active site in addition to the two alternatives
      determined previously (Skirgaila et al., 1998. J. Mol. Biol. 279, 473-481). One
      of the newly identified putative endonucleases from the Mrr family is composed of
      two diverged cleavage domains, which possess both the "typical" D-EXK and the
      "Mrr-like" D-QXK variants of the active site. Among the Mrr homologs there are
      also proteins from yeast, in which restriction phenotype has not been observed,
      suggesting that the free-standing Eukaryotic PD-(D/E)XK superfamily members might
      be implicated in other cellular processes involving enzymatic DNA cleavage.

PMID- 11313146
TI  - Expressed sequence tags from a NaCl-treated Suaeda salsa cDNA library.
AB  - Past efforts to improve plant tolerance to osmotic stress have had limited
      success owing to the genetic complexity of stress responses. The first step
      towards cataloging and categorizing genetically complex abotic stress responses
      is the rapid discovery of genes by the large-scale partial sequencing of randomly
      selected cDNA clones or expressed sequence tags (ESTs). Suaeda salsa, which can
      survive seawater-level salinity, is a favorite halophytic model for salt tolerant
      research. We constructed a NaCl-treated cDNA library of Suaeda salsa and
      sequenced 1048 randomly selected clones, out of which 1016 clones produced
      readable sequences (773 showed homology to previously identified genes, 227
      matched unknown protein coding regions, 16 anomalous sequences or sequences of
      bacterial origin were excluded from further analysis). By sequence analysis we
      identified 492 unique clones: 315 showed homology to previously identified genes,
      177 matched unknown protein coding regions (101 of which have been found before
      in other organisms and 76 are completely novel). All our EST data are available
      on the Internet. We believe that our dbEST and the associated DNA materials will
      be a useful source to scientists engaging in stress-tolerance study.

PMID- 11313147
TI  - Structural characterization of the mouse Foxf1a gene.
AB  - Members in the superfamily of the forkhead/winged-helix transcription factors are
      known to play a critical role in the control of cell differentiation and tissue
      development. To understand the regulation and function of these genes, we have
      initially isolated and characterized the mouse Foxf1a gene, a novel forkhead gene
      predominantly expressed in the lung. The mouse gene consists of two exons with
      the forkhead domain contained in exon 1, and is located at band E1 on chromosome
      8. Amino acid sequence of the mouse protein shares a high degree of homology to
      that of the corresponding human protein. The tissue specificity of expression of
      the mouse gene also resembles that found in the human gene. This gene is
      primarily expressed in the lung, and to a lesser extent in placenta and tissues
      in gastrointestinal tract. The transcription start site was mapped to 113
      nucleotides upstream from the putative translation initiation site. The promoter
      of the mouse gene is highly GC rich and contains neither a CAAT nor a TATA box. A
      series of luciferase report constructs driven by the promoter and various
      deletions in the 5' flanking region of the gene were constructed and employed in
      transient transfection studies using a line of SV40 transformed mouse lymph node
      endothelial cells (SVEC4-10), which express the endogenous Foxf1a gene, and a
      line of mouse hepatoma cells (Hepa 1-6), in which Foxf1a is not expressed. To our
      surprise, these reporter genes are equally active in both cell lines. Further
      studies have shown that the proximal 5' flanking sequence and exon 1 of the
      endogenous gene are highly methylated in Hepa 1-6 cells but not in SVEC4-10
      cells, suggesting that DNA methylation but not cell-specific transcription
      factor(s) regulates cell specificity of gene expression in these cultured cells.

PMID- 11313148
TI  - Expression plasmid with a very tight two-step control: Int/att-mediated gene
      inversion with respect to the stationary promoter.
AB  - A very tightly controlled expression vector was constructed, which was originally
      designed as to be able to use any promoter, constitutive or regulated. Moreover,
      in vector pNH46T1, the repressible P(tac)/P(lac) promoters were used to
      transcribe genes cloned in the proximal multiple cloning site (MCS), which was
      flanked by convergent attB and attP sites. The gene of interest was cloned into
      MCS in the OFF orientation, i.e. facing the promoter(s). In such OFF orientation,
      the cloned gene could not be expressed, and only its anti-sense mRNA could be
      produced. Four strong rrnBT1 terminators, in a tandem arrangement and proximal to
      the N-terminal end of the cloned non-inverted gene, were protecting it from any
      inadvertent transcription originating in the vector. Moreover, the P(tac)/P(lac)
      promoters/operators are controlled by the LacI(q)ts and LacI(+) repressor(s) that
      further reduce the basal gene expression in the uninduced state. When induced,
      the total vector population is converted to the ON orientation by expression of
      the Int function that inverts the attB and attP-flanked MCS including the cloned
      gene. This places the gene under direct control of the P(tac)/P(lac) promoters,
      and thus results in very high expression. An additional feature is the anti
      termination system that consists of the promoter-proximal nutL site and the
      inducible gene N, whose role in the ON state is to overcome the rrnBT1
      terminators and any other adventitiously cloned terminators.

PMID- 11313149
TI  - Glucose 6-phosphate dehydrogenase expression is less prone to variegation when
      driven by its own promoter.
AB  - The ability to transfer permanently genes into mammalian cells makes retroviruses
      suitable vectors for the ultimate purpose of treating inherited genetic disease.
      However, expression of the retrovirally transferred genes is variable (position
      effect and expression variegation) because retroviruses are highly susceptible to
      the influence of the host genome sequences which flank the integration site. We
      have investigated this phenomenon with respect to the human housekeeping enzyme,
      glucose 6-phosphate dehydrogenase (hG6PD). We have constructed retroviral vectors
      in which the hG6PD cDNA is driven by either of two conventional retroviral
      promoters and enhancers from the Moloney Murine Leukemia Virus (MMLV) and the
      Myeloproliferative Sarcoma Virus (MPSV) long terminal repeats (LTR) or by the
      hG6PD own promoter replacing most of enhancer and promoter LTR (GRU5). We have
      compared the activity of retrovirally transferred hG6PD driven by these promoters
      after retroviral integration in bulk cultures and in individual clones of murine
      fibroblasts. The level of hG6PD expressed by the hG6PD promoter of GRU5-G6PD was
      significantly lower than that expressed by conventional retroviral vectors.
      However, analysis of the single copy clones showed less variation of expression
      with GRU5-G6PD (coefficient of variation, CV, 35.5%) than with conventional
      vectors (CV, 58.9%). Thus we have several vectors competent for reliable transfer
      and expression of hG6PD. The hG6PD promoter provides reproducible expression of
      hG6PD and limits the variability of expression. This decreased variability is
      important in order to help ensuring a consistent level of delivery of the needed
      gene product in future therapeutic protocols.

PMID- 11313150
TI  - Cloning and characterization of human ubiquitin-processing protease-43 from
      terminally differentiated human melanoma cells using a rapid subtraction
      hybridization protocol RaSH.
AB  - Defects in growth control and differentiation occur frequently in human cancers.
      In the case of human melanoma cells, treatment with a combination of fibroblast
      interferon (IFN-beta) and the protein kinase C activator mezerein (MEZ) results
      in an irreversible loss of proliferative potential and tumorigenic properties
      with a concomitant induction of terminal differentiation. These changes in
      cellular properties are associated with an induction and suppression in specific
      subsets of genes that occur in a temporal manner. To identify the complete
      repertoire of gene changes occurring during melanoma reversion to a more
      differentiated state a number of molecular approaches are being used. These
      include, subtraction hybridization using temporally spaced cDNA libraries, random
      cDNA isolation and evaluation by reverse Northern blotting and high throughput
      microarray analysis of subtracted cDNA clones. In the present study we have used
      a novel approach, rapid subtraction hybridization (RaSH), to identify and clone
      an additional gene of potential relevance to cancer growth control and terminal
      cell differentiation. RaSH has identified a human ubiquitin-processing protease
      gene, HuUBP43, that is differentially expressed in melanoma cells as a function
      of treatment with IFN-beta or IFN-beta + MEZ. HuUBP43 is a type I interferon
      inducible gene that is upregulated in a diverse panel of normal and tumor cells
      when treated with IFN-beta via the JAK/STAT kinase pathway. This gene may
      contribute to the phenotypic changes induced by IFN-beta during growth arrest and
      differentiation in human melanoma cells and other cell types as well as the
      antiviral and growth inhibitory effects of interferon.

PMID- 11313151
TI  - The mouse lp(A3)/Edg7 lysophosphatidic acid receptor gene: genomic structure,
      chromosomal localization, and expression pattern.
AB  - The extracellular signaling molecule, lysophosphatidic acid (LPA), mediates
      proliferative and morphological effects on cells and has been proposed to be
      involved in several biological processes including neuronal development, wound
      healing, and cancer progression. Three mammalian G protein-coupled receptors,
      encoded by genes designated lp (lysophospholipid) receptor or edg (endothelial
      differentiation gene), mediate the effects of LPA, activating similar (e.g.
      Ca(2+) release) as well as distinct (neurite retraction) responses. To understand
      the evolution and function of LPA receptor genes, we characterized lp(A3)/Edg7 in
      mouse and human and compared the expression pattern with the other two known LPA
      receptor genes (lp(A1)/Edg2 and lp(A2)/Edg4non-mutant). We found mouse and human
      lp(A3) to have nearly identical three-exon genomic structures, with introns
      upstream of the coding region for transmembrane domain (TMD) I and within the
      coding region for TMD VI. This structure is similar to lp(A1) and lp(A2),
      indicating a common ancestral gene with two introns. We localized mouse lp(A3) to
      distal Chromosome 3 near the varitint waddler (Va) gene, in a region syntenic
      with the human lp(A3) chromosomal location (1p22.3-31.1). We found highest
      expression levels of each of the three LPA receptor genes in adult mouse testes,
      relatively high expression levels of lp(A2) and lp(A3) in kidney, and moderate
      expression of lp(A2) and lp(A3) in lung. All lp(A) transcripts were expressed
      during brain development, with lp(A1) and lp(A2) transcripts expressed during the
      embryonic neurogenic period, and lp(A3) transcript during the early postnatal
      period. Our results indicate both overlapping as well as distinct functions of
      lp(A1), lp(A2), and lp(A3).

PMID- 11313152
TI  - Effect of the calcium channel blockers nifedipine and diltiazem on
      pentylenetetrazole kindling-provoked amnesia in rats.
AB  - A large body of research supports the view that memory disturbance is an integral
      part of epilepsy. Deficit in various behaviour tasks has been found in rats
      subjected to experimental epilepsy-pentylenetetrazole (PTZ) kindling. In the
      present study we examined the effect of post-training administered calcium
      channel blockers nifedipine (10 and 40 mg/kg) and diltiazem (10 and 30 mg/kg) on
      amnesia induced by PTZ kindling in shuttle-box- and step-down-trained rats.
      Retention in nifedipine- or diltiazem-treated kindled animals was significantly
      improved compared to the kindled controls. The mechanisms of action of calcium
      antagonists studied is considered. Taken together with the data about calcium
      channel blocker anticonvulsive activity, the results of this study further
      suggest that nifedipine and diltiazem might be useful in the treatment of
      cognitive disorders in epileptic patients.

PMID- 11313153
TI  - Manic symptoms induced by olanzapine.
AB  - We present the case of a never medicated patient with a diagnosis of DSM-IV
      paranoid schizophrenia in which olanzapine therapy induced manic symptoms. The
      latter remitted after drug discontinuation.

PMID- 11313154
TI  - Effect of alpha-adrenoceptor agents on imipramine-induced antinociception in
      nerve-ligated mice.
AB  - In this study, the effects of adrenoceptor agonists and antagonists on
      antinociception induced by imipramine in sciatic-nerve-ligated mice were
      investigated. The response of different doses of morphine, imipramine and
      adrenoceptor agonists and antagonists was examined 14 days after unilateral nerve
      ligation in the hot-plate test. Intraperitoneal injection of different doses of
      morphine (3, 6 and 9 mg/kg), imipramine (10, 20 and 40 mg/kg), the alpha(2)
      adrenoceptor agonist, clonidine (0.05, 0.1 and 0.2 mg/kg) or the alpha(1)
      adrenoceptor agonist, phenylephrine (2, 4 and 8 mg/kg) induced dose-related
      antinociception in both intact and nerve-ligated mice. The antinociception
      induced by morphine but not that of imipramine, clonidine or phenylephrine, in
      nerve-ligated mice was significantly less than that induced in intact animals.
      Imipramine in combination with clonidine tends to induce a higher response, but
      the combination of imipramine with phenylephrine did not lead to significant
      potentiation. The alpha(2)-adrenoceptor antagonist, yohimbine, reduced the
      response induced by imipramine or imipramine plus clonidine in intact and nerve
      ligated animals. However, the alpha(1)-adrenoceptor antagonist, prazosin, did not
      alter imipramine response. It may be concluded that imipramine induced
      antinociception in both intact and nerve-ligated mice through an alpha(2)
      adrenoceptor mechanism(s).

PMID- 11313155
TI  - D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in
      schizophrenia: a PET study.
AB  - OBJECTIVE: Quetiapine is a novel antipsychotic agent with many atypical features,
      including low D(2) and higher 5HT(2A) affinity in vitro, low propensity to induce
      extra-pyramidal side effects and minimal effects on prolactin levels. The purpose
      of this study was to investigate, using positron emission tomography (PET), the
      relationship between plasma concentrations of different doses of quetiapine and
      occupancy of D(2) and 5HT(2A) receptors in schizophrenic patients. METHODS: Five
      patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28
      days, subsequently reduced weekly in a descending-dose schedule. Dopamine D(2)
      and 5HT(2A) occupancies were determined using [(11)C] raclopride and [(11)C] N
      methylspiperone as ligands, respectively, and PET imaging. RESULTS: Mean D(2)
      receptor occupancies of 41 and 30% were observed at quetiapine doses of 750 and
      450 mg/day. At lower dose levels no occupancy could be determined. Quetiapine
      induced a consistently higher degree of 5HT(2A) receptor occupancy, with mean
      occupancies of 74 and 57% at doses of 750 and 450 mg/day, respectively. No EPS
      emerged during the trial and most of the pre-trial EPS resolved during the study.
      CONCLUSIONS: In clinically effective doses, quetiapine induced low occupancy at
      D(2) receptors, which is consistent with atypical antipsychotics such as
      clozapine, and probably explains the lack of EPS observed in this trial.
      Correlations between receptor occupancy and plasma concentrations of quetiapine
      could not be calculated, although receptor occupancy increased with higher plasma
      concentrations for the 450 and 750 mg doses.

PMID- 11313156
TI  - Absence of myoglobinuria in acute psychotic patients with marked elevation in
      serum creatine phosphokinase level.
AB  - Elevated levels of serum creatine phosphokinase, muscular type (CK(MM)) are
      caused primarily by diseased muscle fiber. Acute psychoses are often associated
      with a marked increase in serum CK(MM) levels, though the reason remains obscure.
      Since striated muscle damage is also associated with pigmenturia and
      myoglobinuria, we sought to determine whether the markedly high serum CK level of
      acute psychosis reflects skeletal muscle damage by evaluating urinary myoglobin
      in affected patients. Baseline serum CK was measured on admission in 713
      consecutive acute psychotic inpatients (BPRS> or =40). Those showing a serum CK
      levels above 1000 IU/l on the first 2 days of hospitalization underwent urine
      collection for myoglobin testing. Patients with physical trauma or medical
      conditions known to cause CKemia were excluded. Twenty-five patients were
      eligible for the study. In no case did myoglobinuria or pigmenturia accompany the
      marked CKemia. There is an unexpected dissociation between the robust increase in
      the serum CK(MM) levels and the absence of myoglobinuria in acute psychosis. Our
      negative finding may indicate that the serum CK threshold for myoglobinuria is
      very high (above 10000 IU/l). Alternatively, psychosis-associated CKemia may be
      related to an unknown, nontraumatic, pathophysiological mechanism(s).

PMID- 11313157
TI  - Different fatal toxicity of neuroleptics identified by autopsy.
AB  - Autopsies and toxicological analyses at the Institute of Forensic Medicine
      revealed 85 fatal intoxications with neuroleptics in Vienna from 1991 to 1997. A
      total of 17 cases were linked to a single neuroleptic (NL) alone, while 68 deaths
      were attributed to a combination of NLs with other drugs. The most frequently
      detected agent was prothipendyl (n=41). During the study period the number of
      defined daily doses of high-potency NLs prescribed increased significantly (P< or
      =0.001) due to increased prescribing of new atypical antipsychotics. The quantity
      of intermediate- and low-potency NLs dispensed remained stable. The most
      frequently prescribed NL was haloperidol. The relative toxicities of different
      NLs were calculated by dividing the number of deaths caused by this NL into the
      number of defined daily doses prescribed in the observation period (f-value).
      Single-substance intoxications and multiple-substance intoxications were
      distinguished. The highest f-values were associated with low-potency NLs,
      especially with prothipendyl, chlorprothixene and levomepromazine. Low f-values
      were found for the group of high-potency NLs, including flupentixol,
      fluphenazine, haloperidol and pimozide, as well as olanzapine. Compared to the f
      values for all NLs prescribed, f-values for low-potency NLs were shown to be
      significantly higher concerning single-substance intoxications (P< or = 0.05) and
      multiple-substance intoxications (P < or = 0.001), while f-values for high
      potency NLs were significantly lower (P< or = 0.05 and P< or = 0.001). We are not
      aware of the psychiatric diagnoses in our post-mortem sample. However, the
      present results indicate that careless use of low-potent NLs should be avoided in
      patients with a potential risk of accidental or suicidal overdose.

PMID- 11313158
TI  - Nitric oxide synthase inhibitors cause motor deficits in mice.
AB  - We investigated possible motor effects of 7-nitroindazole (7-NI), an neuronal
      nitric oxide synthase (nNOS) inhibitor, and N(G)-nitro-L-arginine methyl ester (L
      NAME), an non-selective NOS inhibitor in mice using catalepsy and pole tests in
      comparison with dopamine D(2) receptor antagonist, haloperidol. We also studied
      the change in dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic
      acid (HVA) contents of these compounds. The administration of 7-NI and L-NAME (40
      160 mg/kg, s.c.) dose-dependently induced motor deficit in both catalepsy and
      pole tests. The motor deficit induced by 7-NI was more pronounced than the one
      produced by L-NAME. In contrast, haloperidol showed a marked motor deficit in
      mice. Haloperidol showed a marked motor deficit as compared with 7-NI and L-NAME.
      For dopamine, DOPAC and HVA contents, haloperidol exhibited a significant
      decrease in dopamine content and a significant increase in DOPAC and HVA content
      in the striatum. In contrast, 7-NI showed a significant increase in the striatal
      dopamine content. However, 7-NI had no significant change in the striatal DOPAC
      and HVA contents. On the other hand, no significant change in the striatal
      dopamine, DOPAC and HVA contents was observed in L-NAME-treated mice. The present
      study also showed that the motor deficit induced by 7-NI or L-NAME was
      significantly attenuated by the treatment with L-arginine. These results
      demonstrate that NOS inhibitors as well as dopamine D(2) receptor antagonist
      haloperidol can induce motor deficit in mice. The present study also suggests
      that the mechanism in the motor deficit caused by NOS inhibitors may be different
      from that in the motor deficit induced by haloperidol. Furthermore, our findings
      suggest that nNOS may play some role in control of motor behavior.

PMID- 11313159
TI  - A follow up study of suicide attempters: increase of CSF-somatostatin but no
      change in CSF-CRH.
AB  - Concentrations of somatostatin and corticotrophin releasing hormone (CRH),
      measured in cerebrospinal fluid (CSF) have been reported to be low in suicidal
      patients with major depressive disorder (MDD). Often have MDD patients in
      general, high CSF-CRH and low CSF-somatostatin concentrations, which both seem to
      normalise with clinical recovery. The present study was designed to look for CSF
      CRH and CSF-somatostatin alterations along with clinical changes in patients
      studied repeatedly after a suicide attempt. Sixteen patients with different
      diagnoses, initially inpatients after a suicide attempt (baseline), participated.
      Lumbar punctures and ratings according to the Suicidal Assessment Scale (SUAS)
      and the Montgomery-Asberg Depression Rating Scale (MADRS) were performed while
      patients were drug-free (baseline) and after a median of 7 (5 to 9) months. At
      follow up MADRS- and SUAS-scores were significantly decreased (P<0.05), whereas
      CSF-somatostatin was significantly increased (P=0.013) and CSF-CRH had not
      changed significantly. Thus, the patients showed long-lasting low CSF-CRH
      concentrations, in spite of changed CSF-somatostatin concentrations and clinical
      amelioration.

PMID- 11313160
TI  - Involvement of 5-HT(2C) receptors in the anti-immobility effects of
      antidepressants in the forced swimming test in mice.
AB  - Several recent studies have demonstrated that 5-HT(1A), 5-HT(1B) and 5-HT(3)
      receptors were implicated in the mechanism of action of antidepressants in the
      mouse forced swimming test. Despite extensive evidence for a role of 5-HT(2C)
      receptors in depression, the precise role of these receptors in the effects of
      clinically established antidepressants was not directly investigated in the mouse
      forced swimming test. This work was aimed at exploring interactions between
      several doses of Ro 60-0175, a recently available, full and selective 5-HT(2C)
      agonist, and antidepressant drugs in the mouse forced swimming test. Spontaneous
      locomotor activity was measured as an index of intact sensorimotor functions and
      the dose-effect of Ro 60-0175 alone, as well as interactions with several
      antidepressants, such as tricyclic antidepressants (imipramine, desipramine and
      maprotiline) and selective serotonin reuptake inhibitors (paroxetine, citalopram,
      fluoxetine, fluvoxamine and sertraline), were studied in the mouse forced
      swimming test. There was no intrinsic antidepressant-like effect of Ro 60-0175,
      but an impairment in locomotor function was detected when using doses higher than
      4 mg/kg in the mouse. There was a synergistic effect of low doses of Ro 60-0175
      with sub-active doses of imipramine, paroxetine, citalopram and fluvoxamine; an
      antagonism between the highest dose of Ro 60-0175 and the active doses of
      paroxetine and fluoxetine was also detected. There is evidence that 5-HT(2C)
      receptors may be involved in the action of antidepressants which are able to
      boost the concentration of serotonin in the synapse, i.e. SSRIs and imipramine

PMID- 11313161
TI  - Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute
      placebo-controlled sleep laboratory studies with clonazepam.
AB  - Restless legs syndrome (RLS) - a common sensorimotor disorder - and periodic limb
      movement disorder (PLMD) are currently treated with substances of four classes:
      dopaminergic agents, which are considered the drugs of choice, benzodiazepines,
      opioids and anticonvulsants. As their effects on sleep variables differ
      considerably, the aim of the present placebo-controlled sleep laboratory study
      was to measure the acute effects of 1 mg clonazepam on objective and subjective
      sleep and awakening quality in ten RLS and 16 PLMD patients, utilizing
      polysomnography (PSG) and psychometry. Descriptive data analysis demonstrated at
      the confirmatory level concerning three target variables that - as compared with
      placebo - clonazepam significantly improved objective sleep efficiency and
      subjective sleep quality in both patient groups, but failed to reduce the index
      PLM/h of sleep. At the descriptive level, in PLMD clonazepam improved PLM during
      time in bed, REM and wakefulness and showed more significant changes in various
      sleep and awakening measures than in RLS patients, though there were no
      significant inter-group differences. In conclusion, in both PLMD and RLS
      clonazepam exhibited acute therapeutic efficacy regarding insomnia, which is
      quite different from the mode of action of dopamine agonists.

PMID- 11313162
TI  - Noradrenergic dysfunction and antidepressant treatment response.
AB  - The purpose of this study was to investigate differences in outcome following
      treatment with two different antidepressants in depressed patients according to
      their pretreatment hormonal response to clonidine. In all, 62 drug-free DSM-IV
      recurrent major depressed patients and 20 normal controls were studied. Patients
      were subsequently treated for 4 weeks with fluoxetine (n=28), or amitriptyline
      (n=34), and were then classified as responders or nonresponders according to
      their final Hamilton depression scale score. Compared to controls, depressed
      patients showed lower GH response to CLO (DeltaGH) (P<0.0002). One control (5%)
      and 35 depressed patients (56%) had blunted DeltaGH values. The efficacy of the
      two antidepressants was not significantly different: 15 patients responded to AMI
      (44%), seven patients responded to FLUOX (25%) (P>0.15). However, in the subgroup
      of patients with blunted DeltaGH levels, the rate of responders was higher for
      AMI (11/21) compared to FLUOX (1/14) treated patients (P<0.01). These results
      suggest that in depressed patients a blunted GH response to CLO could predict
      antidepressant response.

PMID- 11313163
TI  - Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder.
AB  - BACKGROUND: After considering the effects of 5-HT receptor agonists with
      different binding profiles on the symptoms of obsessive-compulsive disorder
      (OCD), Zohar and Kindler hypothesized that the 5-HT(1D) receptor was implicated
      in this disorder's pathophysiology. METHODS: We explored the 5-HT(1D) hypothesis
      in a 5-day, random, double-blind, placebo-controlled trial of oral sumatriptan
      100 mg/day in medication-free adults with OCD. We hypothesized that sumatriptan,
      a 5-HT(1D) agonist, would diminish 5-HT release, thereby worsening OCD symptoms.
      We further hypothesized that by beginning to desensitize 5-HT(1D) receptors,
      sumatriptan pretreatment would promote a faster response or an increased
      likelihood of response to subsequent treatment with a selective serotonin
      reuptake inhibitor. RESULTS: The five sumatriptan subjects' OCD symptom
      worsening, as measured by the Yale-Brown scale ( upward arrow 17.6% (S.D. 14.6)),
      was significant when compared to the slight symptom decrease in the five placebo
      subjects ( downward arrow 5.2% (S.D. 4.9), P<0.015). The sumatriptan group did
      not exhibit a faster response or greater likelihood of response to a 90-day, open
      label trial of paroxetine. CONCLUSIONS: Longer term studies of the effects of 5
      HT(1D) agonists on OCD symptoms are indicated. Zolmitriptan, a potent 5-HT(1D)
      receptor agonist with better penetration of the blood-brain barrier, may be a
      preferred challenge agent.

PMID- 11313164
TI  - Short-term efficacy of tricyclic antidepressants revisited: a meta-analytic
      study.
AB  - The original data from the placebo-arms and the tricyclic-arms of all parallel
      randomized controlled three-arm studies, which had been conducted in the period
      1979-1991 for a drug under development in order to obtain marketing authorization
      for the indication major depression, were included in a meta-analysis. Thirty-two
      placebo-controlled studies including 4314 patients were analyzed. The intention
      to treat analysis resulted in 46% responders (at least 50% improvement on the
      Hamilton Depression Rating Scale) in the tricyclic antidepressant group and 31%
      in the placebo-group (CI(95%-difference) 11.5-17.1%). The number needed to treat
      for responders was 7 (CI(95%) 5-8). In 10 out of 32 studies, a statistically
      significant difference in favor of tricyclic antidepressant compared to placebo
      was found for responders. The responder rate in the placebo-group varied from 6
      to 52%. We conclude that tricyclic antidepressants are efficacious in the short
      term treatment of major depression. However, the magnitude of the effect is
      rather modest. Because 69% of the placebo-controlled studies with a tricyclic
      antidepressant did not show a statistically significant difference in favor of
      tricyclic antidepressant and the placebo rate varied considerably from study to
      study, equivalence studies with tricyclic antidepressant as comparator without a
      placebo-control are not sufficient for demonstrating efficacy. Therefore in major
      depression, placebo-controlled studies are still necessary to demonstrate
      efficacy.

PMID- 11313165
TI  - Effect of amantadine on weight gain during olanzapine treatment.
AB  - Patients treated with olanzapine may gain weight, especially in the first months
      of therapy. Amantadine (100-300 mg/day) was started in 12 patients having a mean
      weight gain of 7.3 kg during olanzapine treatment. The patients' weight
      stabilised and over 3-6 months they lost an average of 3.5 kg. No clinical
      deterioration occurred and no adverse effects were reported. These observations
      merit confirmation in randomised, controlled trials.

PMID- 11313166
TI  - Blunted adenosine A2a receptor function in platelets in patients with major
      depression.
AB  - There is provisional evidence of involvement of adenosine in depression. In this
      study, the second messenger intracellular calcium response in platelets was
      measured in patients with major depression and controls using spectrofluorometry.
      The primary result of this study was a statistically significantly blunted second
      messenger response to agonist stimulation in the depressed group compared to the
      control group at the 50 and 100 nM and 1 microM dosage levels. This suggests that
      dysregulation of the adenosine A2a receptor may be present in depression.

PMID- 11313167
TI  - Clinical investigation of medicinal products for treatment of amyotrophic lateral
      sclerosis (ALS).

PMID- 11313168
TI  - Potential new agents in the prophylaxis and treatment of chemotherapy-induced
      emesis.

PMID- 11313169
TI  - Integrating the oral fluoropyrimidines into the management of advanced colorectal
      cancer.
AB  - In colorectal cancer, leucovorin-modulated 5-fluorouracil (5-FU) has been the
      mainstay of both adjuvant treatment and treatment of metastatic disease for many
      years. In advanced disease, response rates of 10-43% are reported; efforts to
      improve efficacy through schedule modification, including prolonged infusions,
      have led to limited success. New agents with improved efficacy, tolerability and
      ease of administration are required. Among the newer drugs, irinotecan and
      oxaliplatin are becoming established as first- and second-line treatment for
      advanced disease. Their novel mechanisms of action have proven to be of value in
      5-FU-resistant patients. In tandem with these developments, thymidylate synthase
      inhibition has remained an important objective and oral fluoropyrimidines such as
      capecitabine and UFT (uracil plus tegafur)/leucovorin have been developed with
      this goal in mind. Two large, phase III studies of capecitabine in metastatic
      disease demonstrated objective response rates of 26.6 and 24.8%. UFT/leucovorin
      has also been evaluated in phase III trials, with an 11.7% response rate
      reported. Both agents are being evaluated in combination with oxaliplatin and
      irinotecan, and ultimately oral fluoropyrimidines as monotherapy or combination
      therapy may replace intravenous (i.v.) 5-FU as first-line treatment for
      metastatic colorectal cancer.

PMID- 11313170
TI  - Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L
      754,030, with ondansetron for the prevention of cisplatin-induced emesis.
AB  - Substance P is localised in brainstem regions associated with emesis. Based on
      studies in the ferret, it was postulated that a neurokinin-1 (NK1) receptor
      antagonist would have antiemetic activity as monotherapy in humans receiving
      chemotherapy. L-758,298 is a water-soluble, intravenous (i.v.) prodrug for L
      754,030, a potent and selective NK1 receptor antagonist. This double-blind,
      randomised, active-agent (ondansetron)-controlled study enrolled 53 cisplatin
      naive patients and evaluated the prevention of both acute (0-24 h) and delayed
      (days 2-7) emesis after cisplatin treatment (50-100 mg/m(2)). All patients
      received i.v. L-758,298 (60 or 100 mg) (n=30) or ondansetron (32 mg) (n=23)
      before cisplatin and efficacy was evaluated up to day 7 post-cisplatin. Nausea
      was assessed by means of a four-point ordinal scale at intervals over the 7 day
      period. In the acute period, the proportion of patients without emesis in the L
      758,298 and ondansetron groups was 37 and 52%, respectively (no significant
      difference between the groups). Comparing the distribution of average nausea
      scores over the entire first 24 h revealed no significant difference between the
      groups. In the delayed period, the proportion of patients without emesis in the L
      758,298 and ondansetron treatment groups was 72 and 30%, respectively (P=0.005).
      The distribution of average nausea scores in the delayed period was lower in the
      L-758,298 group compared with the ondansetron group (P=0.15 for the entire
      delayed period and P=0.043 for day 2 only). No serious adverse events were
      attributed to L-758,298. A single dose of L-758,298 substantially suppressed the
      delayed nausea and vomiting characteristic of high dose cisplatin and also
      appeared to reduce acute emesis post-cisplatin. The data also support the
      proposition that the underlying mechanism(s) of acute and delayed emesis are
      different.

PMID- 11313171
TI  - Time delays and related factors in the diagnosis of cutaneous melanoma.
AB  - Delay in melanoma diagnosis was investigated in a population-based sample of 130
      patients. The median time elapsing from the first notice of the lesion to
      excision was 110.5 days. There was no linear correlation between total delay time
      and Breslow-thickness of the diagnosed melanomas (P=0.19). Patient delay, defined
      as the time from first notice of a (change in a) lesion to the first observation
      by a physician, exceeded 2 months in half of all patients. Only 41% of the
      patients consulted a doctor because they were worried about the lesion. Colour
      change and itch were associated with a longer patient delay. There was no
      correlation with age, gender, socio-economic factors, localisation of the lesion
      and the person who first noticed the lesion. In one quarter of all patients, the
      time from first observation by a physician to excision of the lesion exceeded 2.5
      months. This physician delay seemed to be attributed to misdiagnosis and to a
      delay occurring during referral.

PMID- 11313172
TI  - High stromal hyaluronan level is associated with poor differentiation and
      metastasis in prostate cancer.
AB  - Several epithelial tumours accumulate hyaluronan (HA) which promotes cancer cell
      invasion and metastasis. We analysed the expression of HA and its receptor CD44
      and their prognostic value in 166 prostate cancer patients followed up for a mean
      of 13 years; standard deviation (S.D.) 2.7; range 8.7-21.4 years. HA was detected
      with a specific biotinylated probe prepared from cartilage aggrecan and link
      protein, and CD44 with an antibody recognising all forms of CD44. The peri- and
      intratumoral stroma from half of the patients strongly expressed
      immunohistochemically detectable HA in < or = 15% of the stromal area; the
      tumours in the remaining half expressed HA in > 15% of the area. The staining of
      cancer cells for HA was scored positive or negative, and for CD44 the median
      value of 80% of positive tumour cells was used as a cut-off point. The expression
      of HA in cancer cells was weakly associated with perineural infiltration of the
      tumour (P = 0.03) and high Gleason score (P = 0.002). There was also a
      significant inverse relationship between the expression of HA and CD44 in cancer
      cells (P < 0.001). The high level of HA in the peri-and intratumoral stroma was
      related to metastasis, high T-category, high Gleason score, perineural
      infiltration and high mitotic activity of the tumour (for all P < 0.001). There
      was a significant inverse relationship between the expression of CD44 in cancer
      cells and high level of strong expression of HA in the tumour stroma (P < 0.001).
      A low fraction of CD44-positive cells was related to a high TM-category, high
      Gleason score and rapid cell proliferation (for all P < 0.0001; M/V P value =
      0.0013). In the univariate survival analysis, the high level of strong expression
      of HA in tumour stroma predicted an unfavourable outcome in the entire series (P
      = 0.003) and also in the M0 tumours (P = 0.07), while in T1-2 M0 tumours the
      prognostic value did not reach the level of statistical significance (P = 0.1). A
      low fraction of CD44-positive cells predicted a poor outcome in the entire series
      (P < 0.001) and also in M0 tumours (P = 0.003). Cancer cell-associated HA
      expression had no prognostic value in any tumour categories. In the multivariate
      analysis of prognostic factors, HA expression in the cancer cells or in the
      tumour stroma had no additional value to the standard prognostic factors TM
      classification, Gleason score and CD44 expression. Our results show that stromal
      HA accumulation is related to several malignant features and adverse clinical
      outcome in prostate cancer. However, further studies based on uniformly treated
      patient cohorts are needed to establish the clinical significance of these
      findings in current clinical practice.

PMID- 11313173
TI  - Balance between interleukin-10 and interleukin-12 in adult cancer patients with
      or without infections.
AB  - Reliable markers for identifying infections in cancer patients on admission are
      lacking. The utility of the balance between interleukin (IL)-10 and IL-12 was
      analysed in this respect. The infection group (n=56) had higher median serum
      levels of IL-10 (3.8 pg/ml; interquartile range (IQR) 1.7-11.4 pg/ml versus 1.8
      pg/ml; IQR 0.6-4.6 pg/ml; P=0.005) and IL-10 to IL-12 ratio (0.4; IQR 0.06
      4.23pg/ml versus 0.05; IQR 0.02-0.31pg/ml; P<0.001) than the non-infection group
      (n=36). IL-10 and the ratio had the following figures of sensitivity (79%; 95%
      confidence interval (CI) 66-88 versus 39%; 95% CI 27-53), specificity (40%; 95%
      CI 12-74 versus 90%; 95% CI 56-100) and positive predictive value (88%; 95% CI 76
      96 versus 96%; 95% CI 78-100) for identifying infections (56 cases with infection
      and 10 with neoplastic fever), and the corresponding area under curve (AUC)
      values for IL-10 and the ratio in identifying infections in general were 0.58;
      95% CI 0.39-0.78 versus 0.64; 95% CI 0.46-0.82 and in bacteraemia 0.71; 95% CI
      0.50-0.92 versus 0.75; 95% CI 0.58-0.93, respectively. Thus, IL-10 can be used as
      a screening method for identifying infections in cancer patients and the ratio of
      IL-10 to IL-12 for confirming the diagnosis.

PMID- 11313174
TI  - Unexplained rising carcinoembryonic antigen (CEA) in the postoperative
      surveillance of colorectal cancer: the utility of positron emission tomography
      (PET).
AB  - The aim of the study was to evaluate the use of positron emission tomography with
      [18F]-fluorodeoxyglucose (FDG-PET) in patients with unexplained rising
      carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal
      cancer. 50 consecutive patients with elevated CEA levels and a completely normal
      (n=31) or equivocal (n=19) conventional diagnostic work-up (CDW) were
      retrospectively selected. All PET images were reviewed with full knowledge of the
      CDW. The gold standard consisted of histology, or clinical follow-up of more than
      1 year. Recurrent disease was established in 56 lesions in 43 patients. On a
      patient-based analysis, the sensitivity of FDG-PET was 34/43 (79%), and the
      positive predictive value 34/38 (89%). In 14/50 patients (28%), the FDG-PET
      findings led to a surgical resection with curative intent. On a lesion-based
      analysis, FDG-PET detected 42/56 lesions (sensitivity: 75%), the positive
      predictive value was 79% (42/53). These results demonstrate that FDG-PET can have
      a clear impact on patient management in patients with an unexplained elevation in
      CEA levels.

PMID- 11313175
TI  - Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX)
      versus doxorubicin in the treatment of advanced or metastatic soft tissue
      sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.
AB  - CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and
      reduced toxicity compared with standard doxorubicin in other tumour types. In
      this prospective randomised trial, 94 eligible patients with advanced soft-tissue
      sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous
      (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v.
      bolus every 3 weeks). Histological subtypes were evenly matched, 33% were
      leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well
      matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had
      grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia
      occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37
      (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX,
      and the major toxicity with CAELYX was to the skin. Palmar-plantar
      erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%)
      patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non
      haematological grade 3 and 4 toxicities were rare. Confirmed responses were
      observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial
      response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%);
      with the best response being stable disease (NC) in 16 and 18 patients,
      respectively. The reason for the low response rate is unknown, but it may be due
      partly to a high proportion of gastrointestinal stromal tumours. In conclusion,
      CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity
      profile and should be considered for further investigation in combination with
      other agents such as ifosfamide.

PMID- 11313176
TI  - Long-term chemotherapy of HIV-associated Kaposi's sarcoma with liposomal
      doxorubicin.
AB  - The aim of this study was to examine the outcome, adverse events and clinical
      complications of long-term chemotherapy with pegylated liposomal doxorubicin
      (PegLiposomal DOX) for human immunodeficiency virus (HIV)-associated Kaposi's
      sarcoma (KS) in the pre-highly active antiretroviral therapy (HAART) era. A phase
      II study over a 4-year period in a tertiary care university hospital was carried
      out. 52 acquired immunodeficiency syndrome (AIDS)-patients with advanced KS
      received long-term chemotherapy (71+/-51 weeks) with a mean of 22.8+/-18.2 cycles
      and a mean cumulative liposomal doxorubicin dose of 456+/-364 mg/m(2) (120-1040
      mg/m(2)). Tumour burden, duration and dosage of PegLiposomal DOX, adverse events,
      opportunistic infections, immunological parameters and HIV load were measured. A
      complete (10%) or partial response (56%) was achieved while on chemotherapy. 10
      patients (19%) showed stable disease. Tumour progression was observed in 8
      patients (15%). Importantly, chemotherapy with PegLiposomal DOX was also
      successful after previous cytostatic therapy with bleomycin and vincristine. The
      most common adverse events included leucopenia, neutropenia, anaemia, and
      increased liver function tests. 34 patients (65%) developed new opportunistic
      infections and 29 patients (56%) died during the study period. To conclude,
      pegylated liposomal doxorubicin is a safe and effective drug for long-term
      chemotherapy of advanced (AIDS) KS without adverse effects on CD4 cell counts and
      HIV viral load.

PMID- 11313177
TI  - Quality control of radical prostatectomy: a feasibility study.
AB  - The aim of this study was to assess whether the quality of the surgical act could
      be an important prognostic factor for patients undergoing radical prostatectomy.
      This study also aims to investigate whether the surgical quality can be assessed
      by any means. Questionnaires were collected from 23 different institutes
      including 232 radical prostatectomies (RPr) performed for T1T2 prostate cancer.
      Blood loss, duration of surgery, margin status, postoperative prostate specific
      antigen (PSA) and urinary incontinence were analysed and correlated with the
      yearly number of RPr performed. The mean values obtained for each parameter were
      very different in the various centres. The outcome in terms of tumour control and
      incontinence could not be related to a higher or lower number of RPr performed.
      Quality control of RPr is feasible on the basis of an analysis of a few
      parameters, such as surgical margins, postoperative PSA and incontinence, that
      might recognise urologists that perform better or poorer than a proposed average.

PMID- 11313178
TI  - Recruitment of dendritic cells and enhanced antigen-specific immune reactivity in
      cancer patients treated with hr-GM-CSF (Molgramostim) and hr-IL-2. results from a
      phase Ib clinical trial.
AB  - Experimental findings suggest that granulocyte-monocyte-colony stimulating factor
      (GM-CSF) synergistically interacts with interleukin-2 (IL-2) in generating an
      efficient antigen-specific immune response. We evaluated the toxicity, antitumour
      activity and immunobiological effects of human recombinant (hr)-GM-CSF and hr-IL
      2 in 25 cancer patients who subcutaneously (s.c.) received hr-GM-CSF 150
      microg/day for 5 days, followed by hrIL-2 s.c. for 10 days and 15 days rest. Two
      of the most common side-effects were bone pain and fever. Of the 24 patients
      evaluable for response, 3 achieved partial remission, 13 experienced stable
      disease, and 8 progressed. Cytokine treatment increased the number of monocytes,
      dendritic cells (DC), and lymphocytes (memory T cells) in the peripheral blood
      and enhanced the antigen-specific immunoreactivity of these patients. Our results
      show that the hr-GM-CSF and hr-IL-2 combination is active and well tolerated. Its
      biological activity may support tumour associated antigen (TAA)-specific
      anticancer immunotherapy by increasing antigen presenting cell (APC) activity and
      T cell immune competence in vivo.

PMID- 11313179
TI  - Survival from adolescent cancer in Yorkshire, UK.
AB  - The aim of this study was to investigate survival rates for adolescents with
      cancer and identify factors associated with differential long-term prognosis in
      Yorkshire, UK. A survival analysis of a population-based cohort of young adults
      aged 15-24 years, diagnosed with a malignancy in the former Yorkshire Regional
      Health Authority between 1985 and 1994 was carried out. The main outcome was
      death from all causes. Overall survival for the 1097 adolescents with a
      malignancy increased by 30% between 1985-1989 and 1990-1994 (P=0.004). This
      improvement was reflected in most subgroups of cancer. Large scale geographical
      differences in survival rates were observed across Yorkshire, with an increased
      risk of death in North Yorkshire and Humberside of 34% and 45%, respectively,
      compared with West Yorkshire. Small scale analyses showed reduced survival in
      areas of high population density, but no consistent trends were associated with
      socio-economic status. Improved survival from all cancers in young adults over
      the last decade is clearly seen. Reasons for differential survival by
      geographical area are unclear and warrant further investigation.

PMID- 11313180
TI  - Impact of systematic false-negative test results on the performance of faecal
      occult blood screening.
AB  - The impact of systematic false-negative test results on mortality reduction and
      on programme sensitivity of annual faecal occult blood testing in ages 50-84
      years is explored using a microsimulation model. We made calculations for test
      sensitivities of 80, 50 and 30%. In order to reproduce a cancer detection rate of
      2.2 per 1000 at the first screening, the corresponding mean preclinical sojourn
      times had to be 1.42, 2.30 and 3.84 years, respectively. The fraction systematic
      results among the false-negative results is varied between 0 and 100%. With 80%
      test sensitivity, the reduction in mortality due to screening decreases from 25%
      without systematic results to 23% when all false-negative results are systematic
      and the programme sensitivity decreases from 63 to 58%. With 30% test
      sensitivity, mortality reduction decreases from 21 to 11% and programme
      sensitivity decreases from 52 to 27%. The impact of systematic false-negative
      test results is important if annual FOBT screening is considered.

PMID- 11313181
TI  - Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3
      in gastric cancer.
AB  - Vascular endothelial growth factor C (VEGF-C) is the only factor known to cause
      lymphangiogenesis. We studied the correlation between VEGF-C and vascular
      endothelial growth factor receptor-3 (VEGFR-3) expression of 85 primary gastric
      cancers by reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunohistochemistry, and the results were correlated with the number of
      lymphatic vessels, stained with anti-VEGFR-3 antibody. RT-PCR and immunohistology
      demonstrated that VEGF-C was mainly produced from cancer cells, but not from
      stromal elements. Morphologically, VEGFR-3 expression was detected in the
      endothelial cells of the stromal lymphatic vessels. There was a statistically
      positive correlation between the incidence of VEGF-C and VEGFR-3 mRNA expression
      in the primary tumours (P=0.0002). The number of VEGFR-3-positive lymphatic
      vessels in VEGF-C mRNA positive tumours was significantly larger than that in
      VEGF-C-negative tumours. The number of VEGFR-3-positive vessels in the tumour
      stroma was closely related to the grade of lymphatic invasion of gastric cancer.
      These results strongly indicate that VEGF-C may induce the proliferation of
      lymphatic vessels in the stroma of primary gastric cancer via activation of VEGFR
      3, expressed on the endothelial cells of lymphatic vessels. In these
      circumstances, cancer cells can easily invade the lymphatic vessel, because of
      the increase of the contact points of cancer cells with the lymphatic vessels.

PMID- 11313182
TI  - Quantitative estimates of angiogenic and anti-angiogenic activity by laser
      Doppler flowmetry (LDF) and near infra-red spectroscopy (NIRS).
AB  - The use of laser Doppler flowmetry (LDF) and near-infra-red spectroscopy (NIRS)
      for non-invasive in vivo measurements of angiogenic and anti-angiogenic activity
      in nude mice was evaluated. Angiogenic foci were induced in the skin by
      implantation of slow release pellets containing 200 ng basic fibroblast growth
      factor (bFGF). LDF and NIRS recordings from induced foci were significantly
      higher than placebo implants (P<0.05) and controls (P<0.001), proving that LDF
      and NIRS provide measures of angiogenic activity. Correspondingly, by these
      methods, an anti-angiogenic activity was significantly demonstrated in bFGF
      stimulated animals treated with either the specific anti-angiogenic compound TNP
      470 (P<0.05) or the anti-inflammatory agent dexamethasone (P<0.001). We conclude
      that LDF and NIRS, alone or in combination, are useful non-invasive tools for
      early evaluation of angiogenic and anti-angiogenic activity in vivo.

PMID- 11313184
TI  - Abstracts from the 7th International Congress on Oral Cancer. 22-26 April 2001,
      The Hague, The Netherlands.

PMID- 11313183
TI  - The novel trinuclear platinum complex BBR3464 induces a cellular response
      different from cisplatin.
AB  - BBR3464 is a new platinum-based drug non cross-resistant with cisplatin. To
      characterise the cellular basis of BBR3464 cytotoxicity as opposed to cisplatin,
      we performed a comparative study of the two drugs in cisplatin-resistant
      neuroblastoma and astrocytoma cells. In both model systems, BBR3464 proved to be
      more potent than cisplatin and was able to overcome cisplatin resistance. The
      higher potency exhibited by BBR3464 correlated with an increased cellular
      platinum accumulation and DNA-adduct formation. At equitoxic doses, BBR3464
      induced apoptosis to a lesser extent than cisplatin and failed to overcome the
      decreased susceptibility to cisplatin-induced apoptosis in cisplatin-resistant
      cells. Cell cycle analysis showed a dose-dependent G2/M arrest by BBR3464. In
      astrocytoma cells, cisplatin treatment resulted in the upregulation of p53, p21
      and bax, while only p21 induction was observed after BBR3464 treatment. In
      cisplatin-resistant cells, the reduced sensitivity to cisplatin paralleled a
      resistance to the induction of p53/p21 pathway by cisplatin, while the same doses
      of BBR3464 induced p21 to a similar extent in the resistant cells as in the
      parental cells. In conclusion, BBR3464 induces a cellular response that is
      different from cisplatin, supporting the view that the two drugs act through
      different mechanisms. Our data indicate that BBR3464 may be a promising agent in
      the treatment of tumours unresponsive to cisplatin and with a non-functional p53.

PMID- 11313185
TI  - A sensitive homologous radioimmunoassay for human relaxin-2 (h-RLX-2) based on
      antibodies characterized by epitope mapping studies.
AB  - We present a sensitive homologous radioimmunoassay (RIA) for the quantitative
      determination of human relaxin (hRLX) in human serum, plasma, seminal plasma, and
      urine. This assay is based on a rabbit antiserum which was generated using
      recombinant hRLX-2 as immunogen. Using 125I-hRLX-2 as tracer and a total
      incubation time of 20 - 24 hours the radioimmunoassay showed linearity in a range
      of 60 - 4000 ng/l, a lower detection limit of 38 ng/l and a mean recovery rate of
      98.5%. Intraassay variation was 4.0% (mean = 526 ng/l) and 11.9% (mean = 2368
      ng/l), and interassay variation 10.7% (mean = 256 ng/l) and 13.1% (mean = 2368
      ng/l). Using hRLX-2 hexapeptides on polystyrene pins, epitopes recognized by the
      hRLX-2 specific rabbit antiserum were determined experimentally, and compared to
      predicted epitopes. Both methods led to comparable results. The antiserum,
      recognizing different epitopes, showed no cross-reactivity with human insulin,
      hZn-insulin, hIGF-I, hIGF-II, human inhibin alpha-subunit, two different forms of
      seminal plasma inhibin like peptide, spermolaxin, ubiquitin, prolactin, LH, FSH
      and hCG.

PMID- 11313186
TI  - Lipopeptide adjuvants: generation of lactate dehydrogenase isoenzyme-specific
      antibodies for immunochemical diagnosis.
AB  - Lactate dehydrogenase catalyzes the final step in glycolysis, the interconversion
      of pyruvate and lactate. The tetrameric enzyme is composed of one or two subunits
      (H and/or M) resulting in five isoenzyme forms: LDH-H4, -H3M1, -H2M2, -H1M3, and 
      M4. The relative distribution of the LDH isoenzymes is tissue dependent and a
      significant marker for the diagnosis of hepatoma of the liver, myocardial
      infarction, muscular dystrophy, and a wide variety of other acute and chronic
      diseases to be detected by alterations of the LDH isoenzyme pattern in serum.
      Immunochemical approaches to the routine determination of LDH depend on isoenzyme
      specific antibodies. Since the H- and M-subunits for human LDH are highly
      homologous, LDH isoenzyme specific antibodies for immunochemical monitoring are
      hard to generate. Here we present data on the generation and characterization of
      LDH isoenzyme-specific mono- and polyclonal antibodies in different species in
      the presence of lipopeptide adjuvants. Western-Blot and ELISA analysis showed
      that antisera and monoclonal antibodies recognize their homologous antigens with
      high specificity and are therefore suitable for immunochemical monitoring of the
      LDH isoenzymes H4 and M4. In addition, they can be used for the determination of
      LDH isoenzyme specific activity which is an essential prerequisite for online
      amperometric immunosensor monitoring.

PMID- 11313187
TI  - 32-year old patient presenting with autoimmune polyglandular syndrome.
AB  - A 32-year-old student reported fatigue and malaise since two months in the
      absence of specific symptoms. Clinical examination and extensive laboratory
      testing revealed no abnormalities at his first presentation. Some weeks
      thereafter, on re-admission, hyperpigmentation suggestive of Addison's disease
      was observed and pathognomonic autoantibodies directed against the thyroid gland
      and the adrenal cortex were detected. Further evaluation led to the diagnosis
      autoimmune polyglandular deficiency syndrome, also named "Schmidt syndrome",
      comprising adrenocortical insufficiency (Addison's disease) and lymphocytic
      thyroiditis (Hashimoto thyroiditis). The diagnosis of polyglandular insufficiency
      is often delayed due to non-specific symptoms at early disease stages and
      progression may be rapid, culminating in Addisonian crisis under physical stress
      or infection, requiring immediate high-dose hormone replacement therapy. Hence,
      careful re-examination is mandatory to ensure adequate treatment before life
      threatening complications occur. Nowadays this type of disease is classified as
      autoimmune polyglandular syndrome type II (APS type II) with an increased risk of
      developing insulin-dependent diabetes mellitus (IDDM), vitiligo, alopecia,
      pernicious anaemia, coeliac disease, myasthenia gravis and primary hypogonadism.
      The cause of the disease remains obscure but in addition to an autosomal dominant
      trait with variable penetrance some hints at viral infection triggering the
      disease process exist.

PMID- 11313188
TI  - Erythropoiesis after kidney transplantation: the role of erythropoietin, burst
      promoting activity and early erythroid progenitor cells.
AB  - Successful kidney transplantation is followed by the anemia correction due to re
      establishment of normal erythropoietin secretion. The possible role of growth
      factors and cytokines regulating hematopoiesis in this anemia correction are not
      completely understood. The aim of this study was to investigate the role of
      erythropoietin and other stimulators in the regulation of erythropoiesis after
      kidney transplantation. Thirty-six kidney graft recipients with stable graft
      function for more than 12 months were studied. According to the hemoglobin levels
      they were divided into: group 1 (12 patients) with normal graft function (sCr =
      145.2 +/- 15.8 micromol/l) and normal hemoglobin (12.7+/-0.3 g/dl), group 2 (11
      patients) with normal graft function (sCr = 135 +/- 6.5 miromol/l) and
      posttransplant erythrocytosis (Hb = 18.1 +/- 0.2 g/dl) and group 3 (13 patients)
      with chronic graft failure (sCr = 223.7 +/- 28.9 micromol/l, range 181-294) and
      anemia (Hb = 9.0 +/- 0.8 g/dl). Early erythroid progenitors (BFU-E) from
      peripheral blood, serum immunoreactive Epo and burst promoting activity (BPA) in
      PHA-LCM prepared from patients' peripheral blood mononuclear cells were measured
      in all studied patients. The expected Epo for Hb was found normal in patients
      with normal graft function, 10 times higher in patients with PTE and low in
      patients with anemia. BPA in PHA-LCM prepared from PTE was increased in 4/6
      patients, normal in 4/6 anemic patients, but it was decreased in 5 patients with
      normal Hb. The mean values were 20.8 +/- 6.3 in PTE group and 16.2 +/- 6.8 in
      anemic group, and 4.1 +/- 1.8 (at the level of normal controls) in group 1. The
      number of BFU-E derived colonies was low in most patients with normal hemoglobin
      and anemia, and increased in most patients with PTE. Spontaneous BFU-E colonies
      i.e. without Epo added to the cultures were found in 7 of 12 patients with PTE.
      The mean values of BFU-E showed significant differences between patients with PTE
      (17.43 +/- 7.3), and patients with normal hemoglobin and anemia (4.39 +/- 1.2 vs.
      6.5 +/- 1.1). The results presented suggest that inappropriate Epo secretion
      depends on the graft function and is the primarily important regulator that
      caused PTE or anemia after kidney transplantation. Synergistic action of BPA with
      Epo as well as increased sensitivity of early erythroid precursors to these
      stimulators could explained sustained erythropoiesis in PTE patients. The high
      BPA levels in anemic transplant patients with moderate chronic graft failure
      could be beneficial if rHuEpo treatment is applied in this patient group.

PMID- 11313189
TI  - Surfactant proteins D and A in sputum.
AB  - The surfactant proteins SP-D and SP-A are collectins and central components of
      the innate immune system of the peripheral lungs. They bind to carbohydrates on
      microorganisms and promote their removal. In the larger airways their role and
      concentrations are not yet known. Sputum may thus potentially be useful to
      characterize the collectins in this compartment. Induced sputum was obtained from
      healthy adults and spontaneous sputum from patients with cystic fibrosis. ELISA
      and carbohydrate binding assays were used to quantify the amount and functional
      capacity of the collectins in plugs or sol-fractions, prepared by centrifugation
      of the plugs. SP-D and SP-A were detectable in only about 50% of the sputum
      plugs. Varying the salt, detergent and calcium conditions of the assay did not
      improve the results. In samples with reproducibly detectable SP-D or SP-A, their
      carbohydrate binding capacity was zero. Sputum sol fraction and LPS inhibited the
      binding of the collectins to carbohydrate in the presence of calcium. Whereas SP
      D and SP-A are abundant in the peripheral lung, their presence in sputum derived
      from the larger airways is variable and their carbohydrate binding capacity is
      lost.

PMID- 11313190
TI  - Longitudinal study to assess the effectivity of electric and manual toothbrushes
      for children.
AB  - BACKGROUND: Prophylaxis efforts for the maintenance of tooth health led to a
      distinctive decrease in caries frequency with children and young persons. Because
      the toothbrush can still be described as the most important oral hygiene aid,
      possible differences between the effectivity of electric and manual toothbrushes
      should be tested in the present study. Elementary school children had been
      instructed--within a special prophylaxis program--over a period of three years to
      clean their teeth partly with electric partly with manual toothbrushes. MATERIAL
      AND METHODS: In two parallel classes (1st class) of the same elementary school
      (Private Martinusschule Mainz-Gonsenheim) the A-class (n = 24 children) was
      instructed to clean their teeth with a manual toothbrush suitable for children
      (Oral-B, Power Tip, Braun AG, Kronberg, Germany) whereas the B-class (n = 26)
      received electric toothbrushes (Oral-B-7 EB 5 K, Braun AG, Kronberg, Germany).
      Every three months the children were instructed in group-preventive methods in
      school, followed by cleaning instructions, remotivations and the distribution of
      new electric respectively manual toothbrushes. In order to record the influence
      of the intensive quarterly oral hygiene instruction, elementary school children
      (1st class) of the same school type were looked after and examined within the
      yearly group prophylaxis (n = 40). The yearly dental examinations included the
      recording of carious frequency (DMF-T, dmf-t), approximal plaque accumulation
      (API), and the evaluation of the gingival state (GI-Index) as well as the present
      dental restorative materials. RESULTS: After an investigation period of three
      years no essential differences regarding caries frequency, proportion of
      dentitions of natural state of health and plaque involvement were found with the
      children of the respective classes. Children using electric toothbrushes showed
      after 3 years 27% of healthy-natured dentitions on average (46% of the children
      had got API-values of up to 30%) and the children who used manual toothbrushes
      showed 22% of nature-healthy dentitions (52% of the children had got API-values
      of up to 30%) and in 33% of the control children who received instructions only
      once a year healthy-natured dentitions were found after 3 years (75% of the
      children had got API-values of up to 35%). CONCLUSIONS: With regard to caries and
      gingivitis prevalence modern electric toothbrushes for children can be considered
      equally efficient like conventional manual toothbrushes for children with
      children of normal caries risk.

PMID- 11313191
TI  - New developments in interferon therapy.
AB  - As a complex group of naturally occurring proteins and glycoproteins produced by
      different human cells, interferons (IFN's) have initially been detected as the
      first line of defense in the natural course of viral infection. Due to their
      antiproliferative, differentiation-inducing and immunmodulatory properties they
      also were considered important new drugs in the treatment of cancer. The
      introduction of recombinant DNA technology in the late 1970's permitted large
      scale production of highly purified substrates enabling systematic clinical
      investigations. After several decades of interferon research there have been
      peaks and troughs in estimating their therapeutical value. Today the abundant
      data figure as parts of a giant puzzle which have to be assembled. The identified
      molecular structure of IFN-alpha2b may serve as a basis for future IFN drug
      design. The profound knowledge of the endogenous IFN system and its pathological
      disturbances in the natural course of chronic diseases is a 'conditio sine qua
      non' to explain seeming inconsistency as e.g. the 'paradox' role of IFN-alpha in
      HIV-infection. A better understanding of the pathophysiologic function of the
      acid-lability inducing antigen (ALIA) and the physiologic role of the IFN-type I
      induced Mx protein will be helpful on this way. IFN signal transduction via the
      Jak-STAT system reveals mechanisms of action within hematological disorders. In
      these terms, further developments in interferon therapy as well as future design
      of IFN substrates have to apply a strict standard. The article critically reviews
      to which extent actual treatment strategies as the application of IFN-inducers,
      consensus IFN as well as pegylated IFN's fit into therapeutic schedules which
      have to take into account all these novel insights.

PMID- 11313192
TI  - Prenatal diagnosis of congenital heart disease and neonatal outcome--a six years
      experience.
AB  - BACKGROUND: Prenatal diagnosis of congenital heart disease (CHD) is important for
      proper perinatal and neonatal management, as CHD occurs in approximately eight of
      1000 live births. Antenatal detection of cardiac malformations is crucial as
      altered obstetric and neonatal management may be required and the neonate will
      benefit from delivery at a tertiary care center. METHODS: A retrospective
      comparison between pre- and postnatal diagnoses was accomplished. All fetal
      echocardiographic scans performed and CHD's detected postnatally between January
      1994 and December 1999 by the department of obstetrics and gynecology and
      pediatric cardiology - Grosshadern, Munich University Hospital were reviewed.
      RESULTS: The incidence of CHD was 1.5% (116/ 7913). CHD was suspected by prenatal
      ultrasound in 57 fetuses. Postnatally, 116 congenital cardiac anomalies were
      diagnosed. Overall, the intrauterine detection rate was 38% (44/116). 72% (84) of
      the diagnosed anomalies were Septal Defects, 16% (19) disorders of the
      Atrioventricular Valves and 11% (13) Anomalies of the Great Vessels. In 10% (11)
      of fetuses chromosomal abnormalities were found. 8% (9) newborns suffered from
      congenital syndromes. In 55% (64) children were delivered preterm (<37 weeks of
      gestation). 5% (6) of the neonates required surgery within their first year of
      life. 28% (33) of children with CHD did not survive the first year of life.
      CONCLUSION: As the prenatal diagnosis is important for pre-, peri- and postnatal
      management, diagnostic accuracy is essential. Nevertheless, the accuracy of
      postnatal pediatric echo still exceeds that of the prenatal scan.

PMID- 11313193
TI  - Interstitial lung disease induced by endogenous Candida albicans.
AB  - We report on a 64-year old woman with an interstitial lung disease which had
      characteristics of hypersensitivity pneumonitis. Severe febrile attacks with
      impairment of ventilation and diffuse poorly defined radiodensities and ground
      glass opacities on chest x-ray occured repeatedly. Laboratory data showed
      hypoxemia, leukopenia and circulating Candida albicans (C.a.)-antigen.
      Bronchoalveolar lavage revealed an increase in neutrophils. Transbronchial
      biopsies showed lymphocytic alveolitis, bronchiolitis obliterans and epitheloid
      cell granulomas. IgG and IgA and the lymphocyte proliferation assay were positive
      with C.a.-antigen. C.a. was detected in the feces. Intradermal skin test with
      C.a. showed a positive immediate and late phase reaction and inhalative
      provocation test with C.a.-antigen was positive. After antimycotic treatment the
      symptoms resolved completely and long-lasting. We conclude that the disease was
      induced by C.a.-antigen reaching the lungs from the intestinal tract via the
      bloodstream.

PMID- 11313194
TI  - Patients compliance in periodontal therapy: a retrospective investigation on the
      basis of a clinical group.
AB  - PURPOSE: Because periodontal therapies, as shown in numerous studies, are long
      term treatments, the continuous and active cooperation of the patient is
      indispensable. This study focused on the compliance of a large group of patients
      over a longer period of time and aimed to uncover possible factors affecting
      compliance. The possible correlation between the patient's gender and attitudes
      toward oral hygiene was included. Measures of the success of systematic
      periodontal treatment was the basis of evaluation. METHODS: On the basis of
      treatment documentation covering 500 periodontic patients at a University Dental
      Clinic, over a period of 25 years, patient compliance was statistically
      determined, particularly in the recall phase, and the success of treatment was
      related to a number of study parameters. RESULTS: Interruption of treatment was
      recorded in 20% of the cases in the preoperative phase and in 46.4% in the recall
      phase. Regarding compliance, greater interest and more regular participation on
      the part of women was observed. The results demonstrate that compliance in
      domestic oral hygiene--as measured by the pre- and post-therapeutic approximal
      plaques-index-value--was improved by 26%. Comparing the pre- and the post
      therapeutic measurements of the mean probing depths, there was a mean improvement
      of 0.31 mm. CONCLUSIONS: Patient compliance can clearly be improved, first by
      providing more information about the development and consequences of periodontal
      diseases and secondly by institution of a recall system supported by electronic
      data processing.

PMID- 11313195
TI  - Avascular necrosis of both femoral heads in an HIV-infected patient receiving
      protease inhibitors.
AB  - Several adverse effects have been reported under antiretroviral therapy
      containing protease inhibitors. We report a further case of avascular necrosis of
      both femoral heads in an HIV-infected patient treated with protease inhibitor
      containing antiretroviral therapy.

PMID- 11313196
TI  - Transition of adult patients with cystic fibrosis from paediatric to adult care-
      the patients' perspective before and after start-up of an adult clinic.
AB  - Although most patients with cystic fibrosis (CF) survive into adulthood, many CF
      centres are still run by paediatricians. A transition programme from the
      paediatric CF unit to a newly established CF clinic at the Department of Internal
      Medicine was carried out for the whole group of patients > or =18 years. We aimed
      to evaluate our patients' opinion of the transition by analysing the results of
      two surveys performed before and after the transition. Nine months before the
      transition, we mailed an anonymous questionnaire. Statements regarding the
      forthcoming transition were to be answered on scales from 1 to 4, and the
      patients had to check a list of adjectives describing the current treatment in
      the paediatric CF centre as well as the presumed care in the adult unit. Fifteen
      months after the transition, a second survey with similar questions was carried
      out. RESULTS: 44 of 68 patients (65%) aged 18 to 33 years replied to the first
      and 56% of patients to the second questionnaire. Mean duration of treatment at
      the paediatric CF centre was 7.5 years (range: 1 to 22 years). Twelve patients
      each were classified as supporters or opponents of the transition, the remaining
      patients as intermediates. Older patients and those who had not required
      hospitalisation during the preceding year had a more positive attitude to the
      transition (p <0.05). There was a linear relationship between the transition
      attitude score and the presumed quality of care in the Internal Medicine
      Department (r = 0.62, p <0.001), but no relation to the quality of present
      paediatric care (r = -0.09, p = 0.59). In the second survey, patients rated the
      quality of care in the adult CF unit better than prior to the transition.
      CONCLUSIONS: The transition from paediatric to a newly established adult CF
      centre was accepted by most adult CF patients. Thorough training of all staff of
      the new adult unit and a close co-operation between both departments are pre
      requisites to guarantee a smooth transition of all patients.

PMID- 11313197
TI  - [Bcl2-associated X protein].

PMID- 11313198
TI  - [DNA topoisomerase II alpha: what the devil is it doing in the centrosome?].

PMID- 11313199
TI  - [Combretastatin A4 phosphate].

PMID- 11313200
TI  - [Genetic profiling of cancer: what for and when?].

PMID- 11313202
TI  - [Genomics in the understanding of the mechanisms of transcriptional regulation].
AB  - Whole genome" expression profiles can be used as molecular signatures or
      portraits characteristic of a tumour or of the physiological state of a cell.
      This global description also provides a new approach for the study of the
      transcriptional regulation, and this review is dedicated to this fundamental
      aspect of the transcriptome. Gene expression studies will be first considered at
      the single cell level. In situ analyses reveal that transcription is a stochastic
      phenomenon, indicating that the transcriptome contains fluctuating regions. The
      transcriptional response of a cell population to an external stimulus has been
      used to evaluate the contribution of the various signalling pathways and
      transcription factors. One of the emerging themes is the co-ordinate expression
      of genes associated with the same physiological process. In the spirit of this
      analysis of the transcriptional regulatory networks, it is becoming possible to
      design artificial biological networks to implement desired functions, paving the
      way to new therapeutic approaches.

PMID- 11313201
TI  - [DNA arrays: technological aspects and applications].
AB  - The Human Genome Project has allowed considerable progress in the construction of
      physical and genetic maps and the identification of genes involved in human
      sicknesses. The accelerated accumulation of biological information and knowledge
      is due in large part to the sequencing projects of other organisms, which in fact
      paved the way for the Human Genome Project. In parallel, recently developed
      techniques which take advantage of genomic sequences allow large scale molecular
      analyses resulting in the functional annotation of many of the proteins
      represented by these genes. This is the goal of functional genomics. These
      progresses are at the origin of the present revolution in biomedical research.
      DNA microarrays are playing a dominant role compared to the other developing
      technologies since they are relatively easy to make and use and are applicable to
      numerous scientific inquiries. They allow the simultaneous analysis of several
      thousands of genes in biological samples from sick or healthy tissues, at the
      genome or transcriptome level. The data obtained is expected to result in major
      advances in the health sciences. In addition to an improved understanding of the
      complex molecular interaction networks of healthy cells and tissues, a more
      precise genetic characterization of the molecular mechanisms involved in
      pathology should result in the identification of new therapeutic targets and the
      development of new medicines. The genetic profiles thus obtained should also
      permit the definition of new pathologic subclasses not recognizable by
      traditional clinical factors, as well as new markers for susceptibility to
      certain illnesses, and new prognostic markers or methods of predicting responses
      to treatment. In this article, we present the different approaches and potential
      applications of DNA microarray technology, in particular as applied to cancer
      research.

PMID- 11313203
TI  - [Genomic profiling: from molecular cytogenetics to DNA arrays].
AB  - Genetic instability results, in a large majority of solid tumors, in deep
      chromosomal rearrangements. However, because chromosomal instability produces
      highly complex caryotypes, rarely showing stereotypic aberrations, it has not
      been possible to characterize solid cancers according to specific patterns of
      chromosomal rearrangements. This contrasts with the situation in hematological
      malignancies, where cytogenetics has allowed to lay out the basis of a renewed
      classification. New insights have been brought by the development of comparative
      genomic hybridization (CGH). This molecular cytogenetics approach was originally
      devised to detect regions in the genome of tumor cells undergoing quantitative
      changes, i.e. gains or losses of copy numbers. The large body of studies based on
      CGH show that solid tumors undergo frequent gains and losses and that every
      chromosomes show at least one region of anomaly. Furthermore, different tumor
      types present distinct CGH patterns of gains and losses. These observations favor
      the idea that it may be possible to type human solid cancers according to their
      patterns of genomic aberrations. However, despite the fact that a number of CGH
      based studies present data suggesting that different tumor types or cancers at
      different stages of evolution show distinct patterns of gains and losses, it has
      proven difficult to be conclusive. This can be mainly attributed to the lack of
      spatial resolution of CGH. Indeed, CGH uses metaphase chromosomes as
      hybridization targets and therefore its resolution is at the level of chromosomal
      banding. The recent adaptation of DNA array technology to CGH will allow to pass
      this limitation. In DNA array based CGH (array-CGH) metaphase chromosomes have
      been replaced by spots of cloned DNA. These DNA clones may either be genomic
      (BACs, YACs or cosmids) or coding (cDNAs). The resolution of array-CGH is
      therefore determined by the size of the cloned DNA insert (100 Kb for BACs, 1-2
      kb for cDNAs). Data corresponding to each of these clones is or will be in a near
      future linked to DNA sequence data. Hence, in a near future, array-CGH will allow
      to increase the resolution from a cytogenetic level to a molecular level.
      Finally, because array technology is highly adaptable to automation, going from
      classical CGH to array-CGH will produce a quantum leap in throughput.

PMID- 11313204
TI  - [Transcriptome analysis in cancerology: bioinformatics aspects].
AB  - Recent technological advances (e.g. various DNA arrays and chips) allow the
      measurement of expression level (mRNA abundance) for thousand of genes
      simultaneously, over multiple conditions or time. Initially developed and tested
      on model systems such as yeast or in vitro cell line cultures, these techniques
      have recently begun to be applied to the analysis of human cancers. Initial
      results are promising, and large-scale gene expression profiling is now expected
      to become a clinical tool for better tumour identification, prognosis, and
      optimal treatment design. It is thus important that clinicians become familiar
      with the theoretical principles underlying the interpretation of gene expression
      profiles as used in three different contexts: gene discovery, tumour class
      prediction, and molecular diagnosis. This is the purpose of the present article.

PMID- 11313205
TI  - [Molecular typing of breast cancer: transcriptomics and DNA microarrays].
AB  - Breast cancer is the most frequent and deadly cancer of women. Its great
      heterogeneity makes prognosis and response to current treatments highly variable
      and difficult to predict. Mammary oncogenesis remains poorly understood. These
      issues should benefit from recent development of techniques capable of large
      scale molecular analyses. The use of cDNA array techniques allows for the
      simultaneous analysis of the mRNA expression levels of thousands of genes in
      mammary tumor cell lines and breast tumors. Expression profiles will help
      classify tumors and provide new prognostic tools and potential therapeutic
      targets. They will also boost our knowledge of the molecular events responsible
      for the development and progression of this cancer.

PMID- 11313206
TI  - [Genetics of prostate cancer].
AB  - Genetic epidemiology studies have suggested the responsibility of genetic factors
      in prostate cancer susceptibility. The development of genomic and high throughput
      genetic studies has allowed the recent identification or localization of such
      susceptibility genes. Furthermore, these technologies have contributed to
      outstanding advances in somatic genetics of prostate cancer. The goal of the
      present review is to disclose contributing technologies to and results of genetic
      studies of prostate cancer.

PMID- 11313207
TI  - [A functional gene map is required to adapt therapy of metastatic neuroblastoma].
AB  - Neuroblastoma is a very common solid tumor which arises in childhood and shows an
      extreme heterogeneity at the clinical, histological and genetic levels. Besides
      age and stage, N-myc amplification and 1p deletion are prognostic factors of the
      disease: in Europe, these genetic markers are used to conduct therapy. In France,
      N-myc amplification is a factor of bad prognosis which leads, in all forms of the
      disease including localised forms and metastatic forms of children aged of less
      than 1 year, to a myeloablative treatment with autologous hematopoietic stem
      cells transplantation. By contrast, N-myc amplification has no impact on the
      survival of children aged of more than 1 year with a poor prognosis (30% overall
      survival, 5 years) but this genetic abnormality is taken into account to treat
      primary tumor of these patients. In an attempt to find out prognostic factors of
      these aggressive forms of the disease, various pathways (apoptosis,
      differentiation angiogenesis, detoxication, immune response) have been recently
      surveyed, but studies have been carried out on a limited number of genes.
      Moreover, experimental models of human metastatic neuroblastoma have been
      obtained in which variations of genes transcript levels involved in these
      pathways, are observed. The current break-through of cDNA microarrays allows to
      develop a dynamic transcriptomic scanning of these models as well as of tumors
      and bone marrows from patients upon conventional chemotherapy. This technology
      will enable: i) to define molecular entities of the metastatic disease; ii) to
      apply adapted treatment; iii) to develop new therapeutic strategies.

PMID- 11313208
TI  - [Gene expression profiling in human mesothelioma cells using DNA microarray and
      high-density filter array technologies].
AB  - Although the use of asbestos has been banned in most industrialized countries, it
      is still a major public health concern. Asbestos fibers are mutagenic and
      carcinogenic for humans, classified as "carcinogen category 1 (T, R45: can cause
      the cancer)" in the 25th adaptation of the directive 67/548/EEC. In France,
      asbestos is thought to be responsible each year for many pulmonary diseases:
      pleural plaque, bronchogenic carcinoma and mesothelioma (malignant tumor of
      pleura). In order to better understand the transformation process of pleural
      cells, we compared the gene expression of mesothelium cells (Met-5A) and
      mesothelioma cells (MSTO-211H) using high-density filter array (588 genes) and
      microarray (6.969 genes). Results of both technologies were compared and
      expression levels of several genes were confirmed by quantitative RT-PCR. Data
      analysis with GemtoolsTM 2.4 software allows us hierarchical classification of
      genes of known functions by enzyme, function and pathway clusters and leads to
      characterize both malignant and normal phenotypes. Finally, the comparison
      between the two cell lines provides new markers of mesothelioma and pleura. They
      could be useful for diagnostic, prognostic and therapeutic.

PMID- 11313209
TI  - [Gene expression profiling by suppression subtractive hybridization (SSH): a
      example for its application to the study of lymphomas].
AB  - Suppression subtractive hybridization (SSH) was used to isolate genes that were
      differentially expressed in anaplastic lymphoma kinase (ALK)-positive and ALK
      negative anaplastic large cell lymphoma. In addition, this approach was applied
      to Hodgkin's disease cases with different clinical outcomes. SSH combines a
      normalization step that equalizes the abundance of cDNAs within the sequences to
      be tested and a subtraction step that excludes the common sequences between the
      target and the control. In a model system, the SSH technique enriches for rare
      sequences up to 5,000-fold in one round. We have isolated several genes whose
      expression varied significantly with regard to the tumour subtypes. There were
      different genes with known or unknown functions. We aim to compare the results of
      the SSH approach with those obtained with high density filters. In a near future,
      we would like to design DNA chips specific of each pathology that could be used
      for clinical purposes (evaluation of prognosis and therapeutic response).

PMID- 11313210
TI  - [Coordinated organization of symptoms management and support in all the stages of
      cancer disease: putting in place pluridisciplinary structures of supportive
      oncological care].
AB  - The organization of the management of pain and other symptoms all along the
      cancer disease, of psychological support and palliative care is a complex
      question that does not correspond to any perfectly established model, both in
      France and abroad. Different structures are implied in there care and coexist
      with an insufficient coordination: cancerology structures, structures of chronic
      pain management, structures of psycho-oncology, structures of palliative care.
      Some other assistances are more or less isolated inside the hospital: nutritional
      support, social assistance, action against tobacco and other addictions,
      volunteer work. Because of the evolution of practices and mentalities over the
      last ten years, the highlights of evident interfaces and complementary
      activities, the notions of "continuous care" and "integrated care" inside
      conventional departments, the budgetary and organizational restraints, it is now
      possible to propose a model of hospital structure adapted to the problem of
      supportive care. The creation is proposed from preexisting structures,
      consultations, units, departments of supportive oncological care according to the
      size of the institution. The structure should comply with some specifications,
      sometimes regulations, and to coordinate at best different competencies in the
      interest of the patients and medical teams : pain and symptoms management (of
      which palliative care is an important part), psycho-oncology, rehabilitation
      (functional rehabilitation, nutrition, social work, fights against addictions). A
      pooling of technology settings is one of its interest. The model can be applied
      in other domains than cancerology and in most health institutions.

PMID- 11313211
TI  - [Towards the redefinition of the aims of palliative surgery?].

PMID- 11313215
TI  - Anoxic seizures: self-terminating syncopes.
AB  - This review focuses on anoxic seizures induced by self terminating syncopes in
      the young. Anoxic seizures are nonepileptic events consequent upon abrupt
      interruption of the energy supply to metabolically active cerebral neurones.
      Anoxic seizures are the most common paroxysmal events misdiagnosed as epilepsy.
      Neurally mediated syncopes have numerous appellations, especially in the young.
      This proliferation of terminology likely results from uncertainty regarding
      pathophysiology. The most important type of self-limiting syncope from the point
      of view of diagnostic difficulty has been called neurocardiogenic or vasovagal
      syncope and reflex anoxic seizure, amongst other names: this review includes a
      video clip of such a child with prolonged asystole. It also includes a detailed
      case history emphasising the feelings of a patient with this type of syncope who
      was misdiagnosed as having epilepsy for many years. The second class of self
      terminating syncope discussed and illustrated on video is the so-called breath
      holding spell of young children. The third example illustrated is the compulsive
      Valsalva manoeuvre of individuals with autistic spectrum disorder, in which
      anoxic seizures - as shown on the video clips - are easily misdiagnosed as
      epileptic seizures, with unfortunate consequences.

PMID- 11313216
TI  - Startle response: epileptic or non-epileptic? The case for "flash" SMA reflex
      seizures.
AB  - A 19-year-old woman complained of long-standing, frequent, debilitating brusque
      movements triggered by unexpected stimuli. She was neurologically normal and
      neuroimaging was also normal. Conspicuous startle reactions were easily
      reproduced under EEG and video monitoring: the interictal EEG was normal, the
      ictal recordings doubtful; clinically, the startle reaction was asymmetric, with
      elevation of the left limbs. The diagnosis of hyperekplexia and startle epilepsy
      were discussed. We learned that she had been evaluated at age 3-4 months for
      spontaneous, generalised tonic-clonic seizures and "infantile spasms", in fact
      for early-onset startle reactions triggered by noise or contact, in association
      with prominent EEG changes. A full remission had been achieved under ACTH
      therapy, but the startle reactions had reappeared at around age six. The patient
      was successfully treated with carbamazepine. The history, clinical and
      neurophysiological data led us to discuss the diagnosis of hyperekplexia and
      startle epilepsy. We concluded that the patient had an unusual form of
      cryptogenic focal epilepsy originating from the supplementary motor area,
      presenting as strictly stimulus-triggered "flash" seizures.

PMID- 11313217
TI  - Epigastric sensations as an unusual manifestation of adult absence epilepsy.
AB  - We report the case of a 39-year-old woman with onset of daily epigastric
      sensations associated with brief episodes of unresponsive blank stare, which have
      been interpreted as complex partial seizures with occasional secondary
      generalisation. Phenytoin as monotherapy and in combination with valproate had
      not been effective. During video-EEG we recorded typical absences with brief 3
      second spike, and slow-wave discharges of up to 5 seconds, which were recognized
      by the patient herself. All absences were preceded by epigastric sensations.
      There was no indication of focal epilepsy. Monotherapy with valproate
      substantially decreased the frequency of the absences. In conclusion, this case
      is peculiar for several reasons: 1) late onset of absence epilepsy, 2) epigastric
      sensation at onset of absence seizures, 3) recognition of brief "phantom"
      absences and 4) presumable adverse effects of phenytoin.

PMID- 11313218
TI  - Asymmetric tonic seizures with bilateral parietal lesions resembling frontal lobe
      epilepsy.
AB  - We performed long-term video/ EEG monitoring and a single photon emission
      computed tomographic (SPECT) study to clarify generating mechanism of bilateral
      tonic motor seizures resembling seizures generated by the supplementary motor
      area (SMA), in patients with bilateral parietal lesions. We describe 2 patients
      (age 24 and 32 years), with bilateral parietal lesions. Clinically, seizures were
      preceded by lightning sensation in the body, followed by asymmetric tonic
      posturing of both hands and thrashing movements of the feet, lasting for less
      than 1 min. Ictal rhythmic (7-15 Hz) activity at the vertex was observed on the
      EEG in 1 patient. Interictal SPECT in 2 patients showed decreased blood flow in
      both parietal areas, consistent with bilateral parietal abnormalities on T2- and
      T1-weighted MRIs. Ictal SPECT in 1 patient showed increased blood flow in the
      right parietal and frontopolar areas. The present 2 patients had clinically
      asymmetric tonic seizures, most likely resulting from spreading of the ictal
      activity from the parietal lesions via the superior longitudinal fasciculus to
      the SMA. Bilateral, homologous lesions in the parietal area might cause
      disinhibition on the unilateral epileptogenic side.

PMID- 11313219
TI  - Perioral myoclonia with absence seizures: a rare epileptic syndrome.
AB  - We present the clinical and video-EEG data on an epileptic boy whose absence
      seizures with marked perioral movements had started at the age of 1.5 years. From
      age 12 years, he experienced frequent episodes of typical absence status
      epilepticus (ASE) lasting 1-2 hours with marked perioral myoclonia and moderate
      confusion. Initial therapy with carbamazepine was substituted by valproate
      because of worsening of the absence seizures. At the age of 17, the patient was
      admitted to our clinic with his usual, but long lasting ASE attack, accompanied
      by 2 generalized tonic-clonic convulsions. ASE was confirmed with the EEG which
      showed continuous 3 Hz spike and wave paroxysms with occasional normal intervals
      of 1-5 seconds. IV injection of clonazepam improved the clinical and EEG findings
      immediately. Video- EEG examination performed after a few weeks demonstrated
      typical absence seizures with perioral myoclonia. Based on the characteristics of
      seizure semiology, other clinical data and EEG findings, the patient was
      diagnosed as having the syndrome of "perioral myoclonia with absence seizures"
      described by Panayiotopoulos.

PMID- 11313220
TI  - Generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy in
      infancy: a case report of two Italian families.
AB  - "Generalized epilepsy with febrile seizures plus" (GEFS+) syndrome has been
      recently described. This term defines a heterogeneous group of generalized
      epilepsies observed in several members of large pedigree studies. The syndrome
      spectrum has been widened by including others forms of generalized epilepsy. We
      report two Italian families in which the fathers showed febrile seizure plus
      (FS+), and two sons had severe myoclonic epilepsy of infancy (SMEI). The clinical
      setting of each epileptic member of the family will be discussed, focusing on the
      relationship with the GEFS+ group, confirming its wide clinical spectrum. In
      fact, GEFS+ is different from most other epilepsy syndromes as it is defined not
      by a set of associated symptoms but by the genetic transmission of a
      predisposition to febrile convulsions and other seizures, with a variable
      expression in several members of the same pedigree, perhaps due to ionic channel
      dysfunction. SMEI could represent the most severe end of the spectrum.

PMID- 11313221
TI  - Epileptic nystagmus: electroclinical study of a case.
AB  - Epileptic nystagmus (EN) is a rare form of nystagmus that occurs only during
      epileptic seizures. We report a case in which EN was first noted in an 8 year-old
      boy. Neuro-imaging was normal. Sharp waves from the left occipital lobe
      characterised the interictal EEG. Ictal video-EEG showed the aspects of electric
      seizures during clinical manifestations e.g. nystagmus. Ambulatory EEG displayed
      numerous diurnal and nocturnal seizures, but exclusively in REM sleep. After two
      weeks of sodium valproate treatment, the seizures, EEG focus spikes and
      nystagmus, as well as the squint, disappeared. During a two-year follow-up the
      child had no further seizures, EEG was normal and the school performance was
      unaffected. This case has the main features of benign epilepsy, although there
      are unusual features such as epileptic nystagmus, permanent squint, reduction of
      EEG paroxysmal abnormalities during NREM, and the presence of seizures during REM
      sleep. The observation and the significance of EN are discussed with reference to
      the literature.

PMID- 11313222
TI  - Epilepsy-related ambiguity in rating the child behavior checklist and the
      teacher's report form.
AB  - Although the child behavior checklist (CBCL) and the teacher's report form (TRF)
      were not designed for diagnosing psychopathology in children with chronic
      illnesses, they have become extensively used research tools to assess behavioural
      problems in paediatric populations, including children with epilepsy. When
      applied to children with epilepsy, items like "staring blankly" or "twitching"
      can be rated on the basis of seizure features rather than behaviour and, hence,
      render behavioural scores ambiguous. The aims were detection, and evaluation of
      the impact, of CBCL and TRF items eliciting ambiguity when applied to children
      with "epilepsy only" (idiopathic or cryptogenic epilepsy, attending normal
      schools). Experts identified items that give rise to interpretational ambiguity
      of the ratings in epilepsy. By treating ratings on these items as missing values,
      their effect was evaluated in CBCL and TRF scores of 59 schoolchildren with
      "epilepsy only" and age and gender matched healthy classmates. Seven items of the
      CBCL gave rise to ambiguity of which items 5 co-occur on the TRF. Rescoring
      reduced psychopathology scores in children with "epilepsy only", but not in those
      of healthy children: the percentage of patients trespassing the clinical cut off
      score, on at least one of the subscales, reduced from 46 to 23% on the CBCL and
      from 18 to 15% on the TRF. Parents and teachers run the risk of confusing
      behaviour and seizure features when filling out the CBCL and TRF. In "epilepsy
      only", prevalence estimates of psychopathology based on the CBCL and TRF, should
      be considered with some reserve.

PMID- 11313223
TI  - Infantile spasms: the original description of Dr West. 1841.

PMID- 11313224
TI  - Spitting as an ictal event.

PMID- 11313226
TI  - [Mental and behavior disorders in children placed in long term care institutions
      in Hunedoara, Cluj and Timis, Romania].
AB  - This article originated from a descriptive study done in 1992-1993 in Romania.
      The study was initiated and coordinated by the French NGO "Medecins du Monde",
      was directed by three health organizations (the "Observatoire regional de la
      sante de Languedoc-Roussillon", the "Unite 265 INSERM", the Romanian League for
      Mental Health) and was granted by the Romanian government and the European
      Community Commission. There are many publications about children's mental and
      behavioural disorders. But there are few epidemiological studies concerning the
      prevalence of these disorders among children suffering from social difficulties.
      This article explores the prevalence of mental and behavioral disorders among
      Romanian children institutionalized and examines specifically the prevalence
      among children in homes for children ("Casa de Copii") to compare it with similar
      data published in other countries. First, this article explores the prevalence of
      mental and behavioral disorders among a population of 4.692 children
      institutionalized in three Romanian districts in 1992. Second, this article
      examines the prevalence of these disorders among a population of 1.610 children
      institutionalized in homes for children ("Casa de Copii"), i.e. 1,610 children
      ages ranging from 4 to 18 years and suffering from social difficulties. Homes for
      children are out of home care institutions which are specialised neither in
      physical deficiencies nor in mental disorders. From this population, a randomized
      sample of 508 children has been screened by physicians and psychologists based on
      an evaluation protocol. Then each disorder has been coded as a diagnosis,
      according to the Tenth International Disease Classification (WHO). Fifty-four
      percent (54%) of the children institutionalized in homes for children in three
      Romanian districts in 1992 had a main diagnosis of mental or behavioural
      disorder. Third, this article compares our results to the prevalence found in
      other studies. Only three studies could be selected for comparison because they
      were the only ones with the three following criteria: 1) a focus on a population
      of children or a randomized sample of children ages ranging from 4 to 18 years,
      2) a focus on children suffering from social difficulties and living in out of
      home care, 3) disorders evaluated by health professionals or a validated
      methodology. Our results lies within the range of prevalence found in the
      literature (41-70%). A discussion follows regarding methodological matters and
      critiques that may be launched from such a comparative designs. Finally, the high
      frequency of institutionalization in Romania in 1992 illustrates how few
      solutions there were to social difficulties and how exaggerated
      institutionalization was. This was a very different situation compared to Western
      Europe and Northern America. This should not hide, however, the actual
      modifications that took place in Romania. This article concludes with a brief
      description of the modifications which have been generated by the evaluation
      protocol used here.

PMID- 11313227
TI  - [Hepatitis E virus infection in Albania].
AB  - Acute HEV in Albania make up 35.7% of acute non A-non B hepatitis and 2.4% of all
      acute viral hepatitis cases, affecting women more with a 2:1 ratio, and are
      described more frequently in adults (73.3%) older than 35 years. In the general
      population (control group), the prevalence of anti-HEV antibodies increases
      progressively with age, from 1.2% in the younger than 9 years, to 17.7% among the
      over 60, in general the average is of 9.7%. A statistical comparison of anti-HEV
      antibodies in healthy persons younger than 20, and those 20 years old and over is
      significant (p < 0.0001). HEV transmission by blood transfusion, mentioned by
      some authors, could be related to the infection of blood donors. We have not
      found any positive cases in thalassemic children who received between 24 and 169
      transfusions. The prevalence of anti-HEV antibodies in pregnant women is lower
      than in the general population (p < 0.0001). In patients with chronic liver
      disease, in comparison with the general population (control group), there is no
      statistical significant difference (p = NS).

PMID- 11313228
TI  - [Clinical aspects of AIDS at the Calmette hospital in Phnom Penh, Kingdom of
      Cambodia A report on 356 patients hospitalized in the Medicine "B" Department of
      the Calmette Hospital].
AB  - A study on AIDS subjects carried out at the Calmette Hospital in Phnom-Penh
      between the 1st January 97 and the 30th December 98. The objective of this study
      was to describe the most frequent clinical manifestations as well as the
      opportunistic infections according to the 1993 CDC classification (purely
      clinical classification). Three hundred and fifty six AIDS patients hospitalized
      in medicine B were included in our study. A complete file was prepared for each
      subject, specifying his/her social and family situation, profession, sexual
      behavior and history. The clinical condition was specified and the paraclinical
      examinations were recorded. The average age was 35 years with 250 men and 106
      women, i.e. a M/F sex ratio of 2.4. The majority of male contaminations were due
      to sexual relationships with multiple partners, 82%, and women with a single
      partner was of 78%. The use of condoms was of 60% (versus 40% occasional); the
      extent of drug-addiction was 1.12% (4 cases). A history of STD was found in 56%
      of cases. The presenting symptoms most frequently found were asthenia, anorexia,
      fever and weight-loss. In decreasing order, the clinical manifestations often
      associated were: weight-loss > 10% or a catechetic condition 58.70% (209/356),
      fever > 38 degrees C >1 month 53% (189/356), diarrhea (> one month) 41.60%
      (148/356). The most frequent opportunistic infections were: oral candidiasis
      51.40% (183/356) and 40% are oro-oesophageal (oral candidiasis + dysphagia or
      odynphagia), pulmonary and extrapulmonary tuberculoses (TB) 43.50% (155/356)
      (pulmonary TB in 65.16%, TB of the lymph nodes 23.22% and disseminated TB and
      cerebral TB 11.61%), cryptococcal meningitis 11.80% (42/356) and pneumocystosis
      6.50% (23/356), CMV retinitis 1.12% (4/356). The other opportunistic
      manifestations such as toxoplasmosis and Kaposis sarcoma are much more rarely
      encountered due to the difficulties of the paraclinical diagnosis. The mortality
      in the department was of 17.40% (62/356). In conclusions, tuberculosis is the
      most frequent of the opportunistic infections in Cambodia. Cryptococcal
      meningitis is in 3rd place for opportunistic infections. It is the first
      diagnosis that should be evoked in a meningeal irritation.

PMID- 11313229
TI  - [Climate variability and number of deaths attributable to malaria in the Niakhar
      area, Senegal, from 1984 to 1996].
AB  - There are a number of reasons why climate, in certain physical and social
      environments, could have an impact on the epidemiology of malaria. Events, such
      as floods or drought, are related to the number of malaria cases and deaths, both
      seasonally and interannually. At a smaller scale, this study analyses the
      relation between climate variability and the variability in the number of deaths
      attributable to malaria in Niakhar, Senegal. The Niakhar area has a population of
      30,000 and has been under demographic surveillance system since 1984. The
      rainfall in this region is highly seasonal, with a rainfall maximum in August and
      almost no rain between October/November and May/June. In addition to this
      seasonal cycle, rainfall also varies greatly from year to year (interannual
      variation). Over the 13 years, there were 661 deaths attributed to malaria with a
      marked interannual variability (range from 23 to 100, with a median of 43). There
      was also a strong seasonality in mortality, with nearly all deaths (89.1%)
      occurring between August and December. The number of deaths peaks in October, two
      months after the rainfall peak. Standardised monthly values were calculated for
      each climatic series (rainfall, relative humidity, temperature) as well as
      standardised five-month and monthly values of the number of deaths attributed to
      malaria between August and December. Correlation coefficients were calculated
      between these standardised values. The correlation between the variability in
      August rainfall and the variability in the number of deaths attributed to malaria
      between August and December was positive and statistically significant (r =
      +0.61, p = 0.02). In addition, highly significant cross-correlations were found
      between monthly rainfall series and monthly mortality series at one- and two
      month lag (r = + 0.43, p = 0.0004 for one-month lag; r = + 0.26, p = 0.03 for two
      month lag). This correlation is somewhat lower than the correlation of August
      rainfall alone with August to December mortality, but the result adds confidence
      to the signal given the increased degrees of freedom in the analysis. Similar,
      but slightly weaker, results were found when precipitation data were replaced
      with surface humidity data. Results with temperature were less clear; while
      temperature could in some circumstances have a direct impact on malaria, in this
      case here it is possible that the weak negative correlation between malaria
      deaths and temperature arises mainly because precipitation is physically
      connected to both the indices, correlating positively with malaria and negatively
      with temperature. The availability of a continuous demographic and medical survey
      since 1984 in a region of highly variable rainfall has created a rare opportunity
      to analyse with some confidence a climate versus malaria relationship. The
      findings are consistent with our understanding of the proposed link between
      rainfall and conditions for the reproduction of the malaria vector, leading to a
      lag time (here of one to two months) between anomalies of rainfall and deaths
      attributable to malaria. These results may have practical implications in Sub
      Saharan regions marked by a great seasonal and interannual variability in
      rainfall by providing a simple tool to forecast the impact of climate variability
      on malaria mortality.

PMID- 11313230
TI  - [Impact of health education programs on the control of urinary bilharziasis in
      Niger].
AB  - The objective of this study was to assess the effect of health education in the
      control of bilharziasis, as a part of an investigation on anti-urinary
      bilharziasis campaign in Niger. We carried out a survey in two groups of endemic
      villages on the Niger, one group of villages where there are health education
      campaigns (target villages) and a control village (no education campaign). Five
      hundred and seventy-seven people were interviewed in the area. The bilharziasis
      project has been the main source of information on bilharziasis of people in the
      project zone. The awareness of measures to fight against bilharziasis has been
      moderate. Indeed, 46.6% of people interrogated in the project area couldn't cite
      any means for containing bilharziasis. In the area of intervention, 41.5% of
      people interrogated were unaware of the intervention of an intermediate host in
      the transmission of the urinary bilharziasis. The notion of reinfestation remains
      little known. Behaviours that favour the illness were ignored by 1/3 of people
      interrogated in the project area. However, there was an increase in knowledge
      about the illness in the program zone in comparison with the control area.
      Despite the increase in knowledge level, changes in behaviour in relation to the
      illness remained low. Risky behaviour continued in about 2/3 of people
      interrogated. Only 33% of persons of the project area declared having adopted at
      least a single good behaviour. Changes of behaviour are slow to take place.
      Activities of health education must be sustained throughout a long period of time
      for sustainable profits of control actions to occur.

PMID- 11313231
TI  - [Approach to sexuality in an AIDS context in Congo].
AB  - The pandemic due to the human immunodeficiency virus (HIV) is extensive in Sub
      Saharan Africa and especially in Congo. Congo is a small country on the Atlantic
      coast and characterized by plentiful equatorial forests and low population
      density (essentially urban). In Congo, there is a high prevalence of HIV. The
      social and economic consequences of AIDS add to those of a recent civil war in
      1997. There were fratricidal confrontations before and after this period. These
      confrontations have led to a massive exodus of the inhabitants of the capital,
      Brazzaville, to the forests and neighbouring cities, essentially towards Pointe
      Noire. Pointe-Noire, chief place of the region of Kouilou, in the South of the
      country, is the second city of Congo and the economic Capital. It is undoubtedly
      for this reason that it has been globally saved. In this context, a sanitary
      policy of prevention of sexual risky behavior can appear as a challenge. While it
      supposes a better knowledge of the sexual activity of the young people, it cannot
      be dissociated from the analysis of the other factors. These factors can be of
      socio-economic political or cultural order. Thus the influence of cultural
      variables in the field of sexuality is certainly preponderant in African
      countries, where sexuality is taboo. Sexuality is a private matter (personal
      intimacy and the couple), but concerns also the family (in the sense of
      membership in an extended domestic group or in a system of relationship) in its
      aspects related to procreation and to the social field (power, alliances). Such
      individual behaviour can be lived as a questioning of the social order. In this
      article, the authors question the place of sexuality in Congo, particularly based
      on the work of anthropologists [2, 6, 7, 9]. Research in the field of sexuality
      at adolescence is rather recent in France and investigations that have been done
      in Congo these last ten years do not exist. Meetings and exchanges in 1998 with
      high-school pupils and schoolboys and girls of Pointe-Noire, have shown that they
      had a high level of knowledge (about contamination by HIV). On the other hand,
      this has also been associated with a number of beliefs, which are higher than in
      France: relating to the possibilities of interpersonal contagion by saliva (by
      kissing), food. but also a contagion by mosquito bites. Some of these pupils
      (essentially boys) have asked us about the greater risk of contagion when the
      male sexual partner presents an irritation or a wound in the penis. This
      recurring question seemingly concerns a point of knowledge. However a more
      attentive analysis lets us think that there could be various interpretations.
      First of all, if the penis is healthy, the risk is low, nearly absent. The
      concern about a friction or about a wound in the penis could be associated with
      the concept of forbidden sexual positions (similar to animal positions).
      Proscriptions are explained by their traumatic character for the feminine device
      and because they are able to induce an infertility or dystocia (difficult)
      childbirth. Other beliefs have connected the origin of AIDS with prohibited
      sexual practices, committed by foreigners, who passed on them secondarily to the
      natives of the country. They are clearly blamed in their contributions to the
      decline of customs and the corruption of tradition. However this unfavourable
      evolution is not longer only their privilege. Sexual superactivity and "sexual
      wandering" are also concerned. It is dialectic of the pure and the impure. The
      rejection or the stigmatisation of foreign values can allow the group to find its
      led astray identity. Condoms are well known by Congolese pupils, but there is
      mistrust of their use, notably for the "elders", guarantor for the moral order.
      This mistrust is probably connected with the beliefs of risks of infertility,
      infection or weakening of the virile force. Condoms are mechanical barriers, made
      by foreigners, to protect native people from foreign troubles, which foreigners
      generate. The investigation of chains of significant from the primary couple
      "nature/artificial (synthetic)" can establish a bait of understanding. The
      contraceptive action of condoms is a problem. Reproduction remains family
      business. Moreover, the place of the "morality", the official speech of
      condemnation from the Roman Catholic Church and the ambivalent positioning of
      certain Congolese religious congregations does not encourage condom use. Finally,
      one should not neglect their cost compared to the standard of living. The
      religious faith is a source of comfort for many Congolese. AIDS can be lived as a
      spiritual probation that certain traditional healers would have foreseen. Certain
      ideologies can be a source of intolerance for people who transgress "ways of
      life" (alcohol, tobacco, anal sexual intercourse.). The religious congregations
      have invaded the public space. The medical world and the political institutions
      cannot ignore them any more. (ABSTRACT TRUNCATED)

PMID- 11313232
TI  - [Survey on sexual behavior by Congolese and French high-school students in an
      AIDS context].
AB  - The social and economic impact of AIDS add to those of a recent civil war in
      1997. There were fratricidal confrontations before and after this period. Pointe
      Noire, the second city of Congo and the economic Capital, was on the whole
      spared. We carried out a survey of 292 high-school students: 39% of girls and 61%
      of boys, from 14 old to 25 years old (average age of 19 years). They were from 5
      general and technical schools, which are representative of the school recruitment
      of the city of Pointe-Noire. This study made in 1998 was the second part of a
      work achieved in France in 1997 with 1,859 high-school students: 70% of girls and
      30% of boys, mean age 17.7 years, range 15-25 years. They came from 3 general,
      technical and professional schools of two departments of the region "Centre"
      ("Indre-et-Loire" and "Loir-et-Cher"). The material, corresponding to this study,
      is an anonymous self-questionnaire of 55 closed items presented in the form of
      assertions to which the student respond either yes or no. Items investigated: 1)
      pubertal maturation and subjective maturation; 2) different aspects of sexual
      experience in adolescence (components of sexual experience) [9] and 3) sexual
      behaviour (including sexual risk taking). All items have been formulated in the
      most accessible possible way for the youngsters. Previously, in 1996, we had made
      a pre-test with this material near sample of French people from 16 to 68 years
      old. The results of the study highlight that the Congolese youngsters present
      more risk than their French homologues. Although the pubertal status (the
      menarche and the spermarche) occurs slightly later, Congolese boys present a
      greater number of sexual partners and greater sexual precocity. Among 54% of
      Congolese pupils from the sample which had already had a sexual intercourse (68%
      of boys and 42% of girls) versus 52% of French pupils (58% of boys and 49% of
      girls), 88% of the Congolese boys have sexual intercourse at the age of 15,
      versus 72% of the girls at 16.5 versus 65% of the French boys in their 15.5 and
      52% of the girls at 16. These differences are significant (p < 0.001) like all
      the following ones. Congolese students declare more sexual partners (4 during the
      last 12 months and 5 for all their life versus 3.2 and 4.4 for the French
      students); the boys more than the girls (6.5 sexual partners on the whole versus
      3.7 for the girls in Congo and 5.7 versus 3.8 in France). Congolese girls
      generally have fewer sexual relations (over 12 months or during their entire
      life) than French high-school girls (respectively 5.9, 6.9 versus 8.7 and 9.3).
      We can see with French and Congolese students, a "traditional" dichotomy between
      boys and girls: that is to say girls tend to engage later in sexual relations and
      to favour the long and regular relations, while the boys have more short, and
      spaced sentimental relations. The relations of these last ones tend to evolve on
      a more preparatory mode, genital and intermittent, contrary to those girls who
      seem more sentimental and continuous. The use of the condom concerns 72% of the
      French pupils for the first sexual intercourse (74% of boys versus 72% of girls) 
      which is close to results of French reference surveys [1, 3]. On the other hand,
      they are only 39% to make use of it in Congo in this circumstance (36% of the
      boys and 34% of the girls). All Congolese young people present more STD (6%
      versus 4% for the French pupils) and more pregnancy (11% versus 3%). The other
      risky situations appear also more important in Congo: as the fact of having
      sexual intercourse after having drunk too much (6% of case where it arrives
      systematically versus 2% in France); to have sexual intercourse with a injecting
      drug user (4% versus 1%); paying or to have been paid (in a systematic way 7%
      versus 1%). The Congolese answers concerning the recourse to prostitution are
      more dissimilar and alarming concerning Congolese young people, especially if one
      takes into account all the situations where it occurred at least once (29% of the
      boys and 13% of the Congolese girls who declare to have had a sexual intercourse
      by paying (with money). Homosexual relations are more frequent in Congo (4 and 6%
      versus 2 and 3% for France). Homosexual experience concerned 13% of the Congolese
      pupils versus less than 5% of the French ones. The answers concerning a sexual
      partner who is "not sure" (20% in Congo versus 2% in France) can get clearer in
      the Congolese context with an elevated prevalence rate of infection by HIV.
      However, other cultural factors should not be neglected. The same applies for the
      answers relative to the sexual intercourse under duress (29% for Congo versus
      less than 7% in France). The answers relative to the fact of having a sexual
      intercourse with a much older partner (21% versus 13%) do not seem surprising for
      Congo. But it does not free risks. All these elements are not associated with a
      better estimate of the personal risk. (ABSTRACT TRUNCATED)

PMID- 11313233
TI  - [Health program and use of community health workers: the example of scorpion
      envenomation in Tunisia].
AB  - Scorpion envenomation is a public health problem in Tunisia (40.000 cases/year),
      particularly in the zone of central Tunisia (region of Sidi Bouzid). The size of
      the province, its low rate of urbanization and the relatively limited health
      ressources required an anti-scorpion approach based on the implication of
      community health workers. During the year 1997, the 338 health workers who assure
      76% of the emergency points treated 42% of scorpion envenomation cases. In spite
      of the success of the experience, authors discuss "the specialization" of these
      agents whose the contribution to others aspects of primary care could be
      improven. These health workers don't constitute a basic component of the
      organization of health care, but an exceptional measure for special geographical
      considerations.

PMID- 11313234
TI  - [Antimicrobial activity of ciprofloxacin and netilmicin compared to various
      antibiotics in Lome, Togo].
AB  - We report the antimicrobial activity of ciprofloxacin and netilmicin on 577
      strains such as S. aureus, Pseudomonas, E. coli, Salmonella, Proteus, Klebsiella
      and Enterobacter. Isolation and identification were performed by standard
      methods. Disk diffusion tests were performed to evalute the susceptibility. The
      percentage resistance to ciprofloxacin for bacteria was: E. coli = 15%,
      Enterobacter = 13%, Proteus = 10%, Pseudomonas = 9%, S. aureus and Klebsiella =
      4%. The percentage resistance to netilmicin for bacteria was: Pseudomonas = 29%,
      Proteus = 26%, S. aureus = 21%, Enterobacter = 16%, Klebsiella = 14% and E. coli
      = 5%. The antimicrobial activity of ciprofloxacin and netilmicin was higher than
      that of others antibiotics.

PMID- 11313238
TI  - Pharmacologically regulated cell therapy.

PMID- 11313239
TI  - Experiences of donors enrolled in a randomized study of allogeneic bone marrow or
      peripheral blood stem cell transplantation.
AB  - The experiences of 69 (38 marrow and 31 peripheral blood stem cell [PBSC]) donors
      participating in a randomized trial comparing allogeneic bone marrow with PBSC
      transplantation were studied. Marrow was collected by means of standard harvest
      techniques and general or regional anesthesia. PBSC donors were treated with 5 to
      7 days of filgrastim at a dose of 16 microg/kg/d and underwent 1 to 3 days of
      apheresis to obtain 5 x 10(6) CD34(+) cells per kilogram recipient weight. Donors
      completed questionnaires describing their health experiences before, during, and
      then weekly after donation until return to baseline status. Both marrow and PBSC
      donors reported minimal fluctuation in symptoms measuring emotional status. In
      contrast, both groups of donors reported deterioration in physical status
      starting with administration of filgrastim (PBSC donors) or after the marrow
      collection procedure. The symptom burden reported was similar, with pain a
      prominent symptom for both groups. Equivalent mean levels of maximal pain,
      average pain, and pain duration through the day were reported, although toxicity
      peaks occurred at different time points during the harvest procedures. All PBSC
      donors but only 79% of marrow donors reported good physical status by 14 days
      after the harvest procedures. These data demonstrate similar levels of physical
      discomfort for hematopoietic stem cell donors regardless of the collection
      procedure used, but a quicker resolution of symptoms for PBSC donors.

PMID- 11313240
TI  - Morbidity and mortality in adults with idiopathic thrombocytopenic purpura.
AB  - To study outcomes of adults with idiopathic thrombocytopenic purpura (ITP), we
      performed a follow-up study in a cohort of 152 consecutive patients who were
      treated according to a well-defined algorithm. Long-term outcomes were determined
      relative to the response 2 years after diagnosis, because most (93%) patients who
      ultimately attained platelet counts above 30.0 x 10(9)/L (30 000/microL) did so
      within this time frame. Complete follow-up for mortality could be studied in 99%
      of patients and for morbidity in 95% of patients, with a mean of 10.5 years.
      Within 2 years after diagnosis, 4 patients died, 2 were lost to follow-up, and 12
      were reclassified as having secondary immune thrombocytopenia. Of the remaining
      134 patients, 114 (85%) had obtained platelet counts above 30.0 x 10(9)/L while
      all therapies had been discontinued. These patients had a long-term mortality
      risk equal to the general population. Twelve of 134 patients (9%), all with
      severe thrombocytopenia, had refractory disease and suffered a mortality risk of
      4.2 (95% confidence interval, 1.7-10.0). Bleeding and infection equally
      contributed to the death of these patients. Another 8 patients (6%) had platelet
      counts above 30.0 x 10(9)/L while on maintenance therapy. Similar to patients
      with refractory disease, these latter patients had considerably increased ITP
      related hospital admissions, but mortality was only slightly higher than in the
      general population. In conclusion, most adults with ITP have a good outcome with
      infrequent hospital admissions and no excess mortality. The absence of gross
      morbidity and mortality in patients with moderate thrombocytopenia supports
      clinical practice refraining from further treatment.

PMID- 11313241
TI  - New mutations inactivating transferrin receptor 2 in hemochromatosis type 3.
AB  - Hereditary hemochromatosis usually results from C282Y homozygosity in the HFE
      gene on chromosome 6p. Recently, a new type of hemochromatosis (HFE3) has been
      characterized in 2 unrelated Italian families with a disorder linked to 7q.
      Patients with HFE3 have transferrin receptor 2 (TFR2) inactivated by a homozygous
      nonsense mutation (Y250X). Here the identification of 2 new TFR2 mutations is
      reported. In a large inbred family from Campania, a frameshift mutation (84-88
      insC) in exon 2 that causes a premature stop codon (E60X) is identified. In a
      single patient with nonfamilial hemochromatosis, a T-->A transversion (T515A),
      which causes a Methionine-->Lysine substitution at position 172 of the protein
      (M172K), has been characterized. TFR2 gene gives origin to 2 alternatively
      spliced transcripts-the alpha-transcript, which may encode a transmembrane
      protein, and the beta-transcript, a shorter, possibly intracellular variant.
      Based on their positions, the effects of the identified mutations on the 2 TFR2
      forms are expected to differ. Y250X inactivates both transcripts, whereas E60X
      inactivates only the alpha-form. M172K has a complex effect: it causes a missense
      in the alpha-form, but it may also prevent the beta-form production because it
      affects its putative initiation codon. Analysis of the clinical phenotype of 13
      HFE3 homozygotes characterized at the molecular level has shown a variable
      severity, from nonexpressing patients to severe clinical complications. The
      identification of new mutations of TFR2 confirms that this gene is associated
      with iron overload and offers a tool for molecular diagnosis in patients without
      HFE mutations.

PMID- 11313242
TI  - Neutrophil-specific granule deficiency: homozygous recessive inheritance of a
      frameshift mutation in the gene encoding transcription factor CCAAT/enhancer
      binding protein--epsilon.
AB  - Neutrophil-specific granule deficiency (SGD) is a rare congenital disorder. The
      neutrophils of individuals with SGD display atypical bi-lobed nuclei, lack
      expression of all secondary and tertiary granule proteins, and possess defects in
      chemotaxis, disaggregation, receptor up-regulation, and bactericidal activity,
      resulting in frequent and severe bacterial infections. Previously, a homozygous
      mutation in the CCAAT/enhancer binding protein-epsilon (C/EBPepsilon) gene was
      reported for one case of SGD. To substantiate the role of C/EBPepsilon in the
      development of SGD and elucidate its mechanism of inheritance, the mutational
      status of the gene was determined in a second individual. An A-nucleotide
      insertion in the coding region of the C/EBPepsilon gene was detected. This
      mutation completely abolished the predicted translation of all C/EBPepsilon
      isoforms. Microsatellite and nucleotide sequence analyses of the C/EBPepsilon
      locus in the parents of the proband indicated that the disorder may have resulted
      from homozygous recessive inheritance of the mutant allele from an ancestor
      shared by both parents. The mutant C/EBPepsilon(32) protein localized in the
      cytoplasm rather than the nucleus and was unable to activate transcription.
      Consistent with this, a significant decrease in the levels of the messenger RNAs
      (mRNAs) encoding the secondary granule protein human 18-kd cationic antimicrobial
      protein (hCAP-18)/LL-37 and the primary granule protein bactericidal/permeability
      increasing protein were observed in the patient. The hCAP-18 mRNA was induced by
      overexpression of C/EBPepsilon(32) in the human myeloid leukemia cell line, U937,
      supporting the hypothesis that C/EBPepsilon is a key regulator of granule gene
      synthesis. This study strongly implicates mutation of the C/EBPepsilon gene as
      the primary genetic defect involved in the development of neutrophil SGD and
      defines its mechanism of inheritance.

PMID- 11313243
TI  - Fetal hemoglobin in sickle cell anemia: relationship to erythrocyte adhesion
      markers and adhesion.
AB  - To assess whether fetal hemoglobin (HbF) modulates the adhesion of sickle
      erythrocytes to endothelium, children with homozygous sickle cell anemia (SS
      disease) were studied, using this physiologically crucial period to evaluate the
      relationships between HbF and the major erythrocyte adhesion markers. The mean
      level of CD36(+) erythrocytes was 2.59% +/- 2.15% (+/- SD, n = 40) with an
      inverse relationship between CD36 positivity and F cells (R = -0.76, P < .000 00
      002). In univariate analyses, significant correlations with various hematologic
      parameters and age were noted. Multiple regression analyses, however, revealed a
      relationship solely with F cells. Minimal levels of very late activation antigen
      4(+) (VLA4(+)) erythrocytes (0.31% +/- 0.45%, n = 40) with relationships similar
      to those noted for CD36(+) cells were also observed. The subpopulation of
      strongly adhesive stress reticulocytes was further assessed, using CD71 as their
      marker. The mean level of CD71(+) erythrocytes was 5.81% +/- 4.21%, with
      statistical correlates in univariate and multivariate analyses similar to those
      discussed above. When adhesion ratios were evaluated, inverse correlations were
      noted between basal and plasma-induced adhesion and F-cell numbers (R = -0.54, P
      < .0005; R = -0.53, P < .0006, n = 39). In addition, in analyses where basal or
      plasma-induced adhesion was the dependent variable and the independent variables
      included F cells and the various adhesion-related parameters, significant
      relationships solely with F cells were noted. The results demonstrate that SS
      patients with higher levels of F cells have concomitant decreases in the numbers
      of CD36(+), VLA4(+), and CD71(+) erythrocytes and that these findings translate
      into less adherent erythrocytes. These findings extend knowledge regarding the
      protective effects of HbF in the pathophysiology of sickle cell disease.

PMID- 11313244
TI  - High response rate in refractory and poor-risk multiple myeloma after
      allotransplantation using a nonmyeloablative conditioning regimen and donor
      lymphocyte infusions.
AB  - Standard allogeneic stem cell transplant (allo-SCT) regimens have been associated
      with a high transplant-related mortality (TRM) in multiple myeloma (MM).
      Nonmyeloablative therapy can establish stable engraftment after allo-SCT and
      maintain the antitumor effect with less toxicity, which is important in heavily
      pretreated and elderly patients. We report on 16 poor-risk MM patients receiving
      allo-SCT from an HLA-matched (n = 14) or mismatched (n = 2) sibling following
      conditioning with melphalan 100 mg/m(2) (MEL-100). Ten patients had refractory
      relapse, 4 responsive relapse, and 2 patients were in near complete remission
      (nCR) with poor-prognosis disease. Patients had received 1 (n = 9) or 2 (n = 7)
      prior autotransplants. Donor lymphocyte infusions (DLIs) were given to 14
      patients with no clinical evidence of graft versus host disease (GVHD) either to
      attain full donor chimerism (n = 4) or to eradicate residual disease (n = 10).
      Fifteen patients showed myeloid engraftment, and 12 patients were full donor
      chimeras at day +21. No TRM was observed during the first 100 days. Acute GVHD
      developed in 10 patients; 1 had fatal grade IV GVHD. Seven progressed to chronic
      GVHD, limited in 3 and extensive in 4 patients. At a median follow-up of 1 year,
      5 patients achieved and sustained CR, 3 nCR, and 4 partial remission. Of 4
      patients progressing after transplantation, 3 achieved a remission following
      further chemotherapy and DLI. Remarkable graft versus myeloma responses were seen
      in chemotherapy-refractory patients. Two patients died of progressive disease,
      and 3 died of GVHD complications without active disease. GVHD remains a major
      problem with this procedure.

PMID- 11313245
TI  - Influence of the hematopoietic stem cell source on early immunohematologic
      reconstitution after allogeneic transplantation.
AB  - Several acute hemolysis episodes, sometimes lethal, have been recently described
      after transplantation of allogeneic peripheral blood hematopoietic stem cells
      (PBHSCs). Hemolysis resulted from the production of donor-derived antibodies
      (Abs) directed at ABO antigens (Ags) present on recipient red blood cells (RBCs).
      A multicenter randomized phase III clinical study comparing allogeneic PBHSC
      transplantation (PBHSCT) versus bone marrow hematopoietic stem cell
      transplantation (BMHSCT) has been conducted in France. In the course of this
      study, serum anti-A and/or anti-B Ab titers were compared before the conditioning
      regimen and on day +30 after transplantation in 49 consecutive evaluable PBHSCT
      (n = 21) or BMHSCT (n = 28) recipients. PBHSCT resulted in a higher frequency of
      increased anti-A and/or anti-B Ab titers 30 days after transplantation as
      compared to BMHSCT: 8 (38%) of 21 versus 3 (11%) of 28 (P =.04). In PBHSCT
      recipients, increased titers were observed mostly after receiving a minor ABO
      mismatch transplant: 5 of 7 versus 3 of 14 in the absence of any minor ABO
      mismatch (P =.05), whereas this was not the case after BMHSCT: 1 of 8 versus 2 of
      20. Anti-A and/or anti-B serum Abs detectable at day +30 after PBHSCT were always
      directed against A and/or B Ags absent both on donor and recipient RBCs. Finally,
      3 of 21 PBHSCT versus 0 of 28 BMHSCT recipients developed anti-allogeneic RBC Abs
      other than ABO (P =.07). Overall, the data strongly suggest that
      immunohematologic reconstitution differs significantly after granulocyte colony
      stimulating factor-mobilized PBHSCT when compared to BMHSCT. Such a difference
      could contribute to the acute hemolysis described after PBHSCT as well as to
      distinct alloreactivity after PBHSCT.

PMID- 11313246
TI  - Stromal cell-derived factor 1alpha increases polyploidization of megakaryocytes
      generated by human hematopoietic progenitor cells.
AB  - The alpha chemokine receptor CXCR4 has been shown to be expressed on human
      hematopoietic progenitor cells and during the megakaryocytic differentiation
      pathway. Stromal cell-derived factor 1 (SDF-1) is the ligand for CXCR4. In this
      study, the role of SDF-1alpha in megakaryocytopoiesis was investigated. CD34(+)
      progenitors purified from peripheral blood were grown in serum-free liquid
      suspension culture supplemented with thrombopoietin to obtain a virtually pure
      megakaryocytic progeny. In this condition, the addition of SDF-1alpha gives rise
      to megakaryocytes (MKs) showing an increased DNA content and a rise of lobated
      nuclei, as compared with untreated cells: at day 5, approximately 20% of the
      cells already showed the presence of more than one nuclear lobe versus fewer than
      5% in the control cells; at day 12, approximately 85% of the cells were of large
      size and markedly polyploid, whereas approximately 60% of the control cells were
      polyploid, showed fewer lobes, and were a smaller size. This effect was dose
      dependent and did not affect the megakaryocytic proliferation. Experiments with
      the mitogen-activated protein kinase (MAPK) inhibitor PD98059 suggested a role
      for MAPK pathway on SDF-1alpha-induced endomitosis. Furthermore, SDF-1alpha
      induced a significant increase in the number of proplatelet-bearing MKs and
      promoted the migration of megakaryocytic cells. Treatment with SDF-1alpha caused
      reduction in CXCR4 abundance on the plasma membrane, seemingly owing to receptor
      internalization. Furthermore, the presence of SDF-1alpha did not affect the
      expression of megakaryocytic markers, indicating that differentiation and
      polyploidization are independently regulated events.

PMID- 11313247
TI  - Ionizing radiation sensitizes erythroleukemic cells but not normal erythroblasts
      to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)--mediated
      cytotoxicity by selective up-regulation of TRAIL-R1.
AB  - Cytotoxic activity of tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL/Apo-2 ligand), used alone or in different combinations with either a low
      (1.5 Gy) or a high (15 Gy) single dose of ionizing radiation (IR), was
      investigated on erythroleukemic cells (K562, HEL, Friend, primary leukemic
      erythroblasts) and on primary CD34(+)-derived normal erythroblasts. Human
      recombinant TRAIL alone variably affected the survival/growth of erythroleukemic
      cells; K562 cells were the most sensitive. Moreover, all erythroleukemic cells
      were radio-resistant, as demonstrated by the fact that cytotoxicity was evident
      only after treatment with high-dose (15 Gy) IR. Remarkably, when IR and TRAIL
      were used in combination, an additive effect was noticed in all erythroleukemic
      cells. Augmentation of TRAIL-induced cell death by IR was observed with both low
      and high IR doses and required the sequential treatment of IR 3 to 6 hours before
      the addition of TRAIL. Conversely, both TRAIL and IR showed a moderate
      cytotoxicity on primary CD34(+)-derived normal erythroblasts when used alone, but
      their combination did not show any additive effect. Moreover, the cytotoxicity of
      IR plus TRAIL observed in erythroleukemic cells was accompanied by the selective
      up-regulation of the surface expression of TRAIL-R1 (DR4), and it was completely
      blocked by the z-Val-Ala-Asp (OMe)-CH(2) (z-VAD-fmk) caspase inhibitor. On the
      other hand, the surface expression of TRAIL-R1 in CD34(+)-derived normal
      erythroblasts was unaffected by IR, which induced the up-regulation of the decoy
      TRAIL-R3. These data demonstrate that treatment with IR provides an approach to
      selectively sensitize erythroleukemic cells, but not normal erythroblasts, to
      TRAIL-induced apoptosis through the functional up-regulation of TRAIL-R1.

PMID- 11313248
TI  - The influence of INK4 proteins on growth and self-renewal kinetics of
      hematopoietic progenitor cells.
AB  - This study investigated the influence of expression of proteins of the INK4
      family, particularly p16, on the growth and self-renewal kinetics of
      hematopoietic cells. First, retrovirus-mediated gene transfer (RMGT) was used to
      restore p16(INK4a) expression in the p16(INK4a)-deficient lymphoid and myeloid
      cell lines BV173 and K562, and it was confirmed that this inhibited their growth.
      Second, to sequester p16(INK4a) and related INK4 proteins, cyclin-dependent
      kinase 4 (CDK4) was retrovirally transduced into normal human CD34(+) bone marrow
      cells and then cultured in myeloid colony-forming cell (CFC) assays. The growth
      of CDK4-transduced colonies was more rapid; the cell-doubling time was reduced;
      and, upon replating, the colonies produced greater yields of secondary colonies
      than mock-untransduced controls. Third, colony formation was compared by marrow
      cells from p16(INK4a-/-) mice and wild-type mice. The results from p16(INK4a-/-)
      marrow were similar to those from CDK4-transduced human CFCs, in terms of growth
      rate and replating ability, and were partially reversed by RMGT of p16(INK4a).
      Lines of immature granulocytic cells were raised from 15 individual colonies
      grown from the marrow of p16(INK4a-/-) mice. These had a high colony-forming
      ability (15%) and replating efficiency (96.7%). The p16(INK4a-/-) cell lines
      readily became growth factor-independent upon cytokine deprivation. Taken
      together, these results demonstrate that loss of INK4 proteins, in particular
      p16(INK4a), increases the growth rate of myeloid colonies in vitro and, more
      importantly, confers an increased ability for clonal expansion on hematopoietic
      progenitor cells.

PMID- 11313249
TI  - A novel myeloid-restricted zebrafish CCAAT/enhancer-binding protein with a potent
      transcriptional activation domain.
AB  - The CCAAT/enhancer-binding protein (C/EBP) family consists of transcription
      factors essential for hematopoiesis. The defining feature of the C/EBPs is a
      highly conserved carboxy-terminal bZIP domain that is necessary and sufficient
      for dimerization and DNA binding, whereas their amino-terminal domains are
      unique. This study reports a novel c/ebp gene (c/ebp1) from zebrafish that
      encodes a protein homologous to mammalian C/EBPs within the bZIP domain, but with
      an amino terminus lacking homology to any C/EBP or to any known sequence. In
      zebrafish embryos, c/ebp1 expression was initially observed in cells within the
      yolk sac circulation valley at approximately the 16-to 18-somite stage, and at 24
      hours postfertilization (hpf), also in circulating cells. Most c/ebp1(+) cells
      also expressed a known early macrophage marker, leukocyte-specific plastin (l
      plastin). Expression of both markers was lost in cloche, a mutant affecting
      hematopoiesis at the level of the hemangioblast. Expression of both markers was
      retained in m683 and spadetail, mutants affecting erythropoiesis, but not
      myelopoiesis. Further, c/ebp1 expression was lost in a mutant with defective
      myelopoiesis, but intact erythropoiesis. These data suggest that c/ebp1 is
      expressed exclusively in myeloid cells. In electrophoretic mobility shift assays,
      c/ebp1 was able to bind a C/EBP consensus DNA site. Further, a chimeric protein
      containing the amino-terminal domain of c/ebp1 fused to the DNA-binding domain of
      GAL4 induced a GAL4 reporter 4000-fold in NIH3T3 cells. These results suggest
      that c/ebp1 is a novel member of the C/EBP family that may function as a potent
      transcriptional activator in myeloid cells.

PMID- 11313250
TI  - Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells.
AB  - The effects of activation of adult murine stem cells on their expression of CD38
      were studied using a murine transplantation model. First, the published finding
      that the majority of long-term engrafting cells from normal adult steady-state
      marrow are CD38(+) was confirmed. Next, it was determined that the majority of
      stem cells activated in vivo by injection of 5-fluorouracil (5-FU) or mobilized
      by granulocyte colony-stimulating factor are CD38(-). Stem cells that were
      activated in culture with interleukin-11 and steel factor were also CD38(-).
      Previous studies have shown that expression of CD34 by adult stem cells is also
      modulated by in vivo or in vitro activation. To determine whether there is
      reciprocal expression of CD38 and CD34, 4 populations of post-5-FU marrow cells
      were analyzed. The majority of the stem cells were in the CD38(-)CD34(+)
      fraction. However, secondary transplantation experiments indicated that when the
      bone marrow reaches steady state, the majority of the stem cells become
      CD38(+)CD34(-). In addition, the minority populations of CD34(+) stem cells that
      occur in steady-state bone marrow are CD38(-). This reversible and reciprocal
      expression of CD38 and CD34 by murine stem cells may have implications for the
      phenotypes of human stem cells.

PMID- 11313251
TI  - Differential requirement for the transcription factor PU.1 in the generation of
      natural killer cells versus B and T cells.
AB  - PU.1 is a member of the Ets family of transcription factors required for the
      development of various lymphoid and myeloid cell lineages, but its role in
      natural killer (NK) cell development is not known. The study shows that PU.1 is
      expressed in NK cells and that, on cell transfer into alymphoid Rag2/gammac(-/-)
      mice, hematopoietic progenitors of PU.1(-/-) fetal liver cells could generate
      functional NK cells but not B or T cells. Nevertheless, the numbers of bone
      marrow NK cell precursors and splenic mature NK cells were reduced compared to
      controls. Moreover, PU.1(-/-) NK cells displayed reduced expression of the
      receptors for stem cell factor and interleukin (IL)-7, suggesting a nonredundant
      role for PU.1 in regulating the expression of these cytokine receptor genes
      during NK cell development. PU.1(-/-) NK cells also showed defective expression
      of inhibitory and activating members of the Ly49 family and failed to proliferate
      in response to IL-2 and IL-12. Thus, despite the less stringent requirement for
      PU.1 in NK cell development compared to B and T cells, PU.1 regulates NK cell
      differentiation and homeostasis.

PMID- 11313252
TI  - CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk.
AB  - Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia are caused by
      mutations of the WAS protein (WASP) gene. WASP may be involved in the regulation
      of podosome, an actin-rich dynamic cell adhesion structure formed by various
      types of cells. The molecular links between WASP and podosomes or other cell
      adhesion structures are unknown. Platelets express an SH2-SH3 adapter molecule,
      CrkL, that can directly associate with paxillin, which is localized in podosomes.
      The hypothesis that CrkL binds to WASP was, therefore, tested. Results from
      coprecipitation experiments using anti-CrkL and GST-fusion proteins suggest that
      CrkL binds to WASP through its SH3 domain and that the binding was not affected
      by WASP tyrosine phosphorylation. The binding of GST-fusion SH3 domain of PSTPIP1
      in vitro was also not affected by WASP tyrosine phosphorylation, suggesting that
      the binding of the SH3 domains to WASP is not inhibited by tyrosine
      phosphorylation of WASP. Anti-CrkL also coprecipitates a 72-kd protein, which was
      identified as syk tyrosine kinase, critical for collagen induced-platelet
      activation. CrkL immunoprecipitates contain kinase-active syk, as evidenced by an
      in vitro kinase assay. Coprecipitation experiments using GST-fusion CrkL proteins
      suggest that both SH2 and SH3 domains of CrkL are involved in the binding of CrkL
      to syk. WASP, CrkL, syk, and paxillin-like Hic-5 incorporated to platelet
      cytoskeleton after platelet aggregation. Thus, CrkL is a novel molecular adapter
      for WASP and syk and may potentially transfer these molecules to the cytoskeleton
      through association with cytoskeletal proteins such as Hic-5.

PMID- 11313253
TI  - Competition between normal [674C] and mutant [674R] subunits: role of the
      molecular chaperone BiP in the processing of GPIIb-IIIa complexes.
AB  - This work aimed at investigating the function of the [C674R] mutation in GPIIb
      that disrupts the intramolecular 674 to 687 disulfide bridge. Individuals
      heterozygous for this mutation show a platelet GPIIb-IIIa content approximately
      30% of normal controls, which is less than expected from one normal functioning
      allele. Coexpression of normal [674C]GPIIb and mutant [674R]GPIIb with normal
      GPIIIa produced a [674R]GPIIb concentration-dependent inhibition of surface
      exposure of GPIIb-IIIa complexes in Chinese hamster ovary (CHO) cells, suggesting
      that [674R]GPIIb interferes with the association and/or intracellular trafficking
      of normal subunits. Mutation of either 674C or 687C had similar effects in
      reducing the surface exposure of GPIIb-IIIa. However, substitution of 674C for A
      produced a much lesser inhibition than R, suggesting that a positive-charged
      residue at that position renders a less efficient subunit conformation. The
      mutant [674R]GPIIb but not normal GPIIb was found associated with the endoplasmic
      reticulum chaperone BiP in transiently transfected CHO cells. BiP was also found
      associated with [674R]GPIIb-IIIa heterodimers, but not with normal GPIIIa or
      normal heterodimers. Overexpression of BiP did not increase the surface exposure
      of [674R]GPIIb-IIIa complexes, indicating that its availability was not a
      limiting step. Platelets from the thrombasthenic patient expressing [674R]GPIIb
      IIIa were found to bind soluble fibrinogen in response to physiologic agonists or
      dithiothreitol treatment. Thus, the [674R]GPIIb mutation leads to a retardation
      of the secretory pathway, most likely related to its binding to the molecular
      chaperone BiP, with the result of a defective number of functional GPIIb-IIIa
      receptors in the cell surface.

PMID- 11313254
TI  - Fibrinogen binding to the integrin alpha(IIb)beta(3) modulates store-mediated
      calcium entry in human platelets.
AB  - Effects of the occupation of integrin alpha(IIb)beta(3) by fibrinogen on Ca(++)
      signaling in fura-2-loaded human platelets were investigated. Adding fibrinogen
      to washed platelet suspensions inhibited increases in cytosolic [Ca(++)]
      concentrations ([Ca(++)](i)) evoked by adenosine diphosphate (ADP) and thrombin
      in a concentration-dependent manner in the presence of external Ca(++) but not in
      the absence of external Ca(++) or in the presence of the nonselective cation
      channel blocker SKF96365, indicating selective inhibition of Ca(++) entry.
      Fibrinogen also inhibited store-mediated Ca(++) entry (SMCE) activated after
      Ca(++) store depletion using thapsigargin. The inhibitory effect of fibrinogen
      was reversed if fibrinogen binding to alpha(IIb)beta(3) was blocked using RDGS or
      abciximab and was absent in platelets from patients homozygous for Glanzmann
      thrombasthenia. Fibrinogen was without effect on SMCE once activated. Activation
      of SMCE in platelets occurs through conformational coupling between the
      intracellular stores and the plasma membrane and requires remodeling of the actin
      cytoskeleton. Fibrinogen inhibited actin polymerization evoked by ADP or
      thapsigargin in control cells and in cells loaded with the Ca(++) chelator
      dimethyl BAPTA. It also inhibited the translocation of the tyrosine kinase
      p60(src) to the cytoskeleton. These results indicate that the binding of
      fibrinogen to integrin alpha(IIb)beta(3) inhibits the activation of SMCE in
      platelets by a mechanism that may involve modulation of the reorganization of the
      actin cytoskeleton and the cytoskeletal association of p60(src). This action may
      be important in intrinsic negative feedback to prevent the further activation of
      platelets subjected.

PMID- 11313255
TI  - The upstream stimulatory factor-2a inhibits plasminogen activator inhibitor-1
      gene expression by binding to a promoter element adjacent to the hypoxia
      inducible factor-1 binding site.
AB  - Plasminogen activator inhibitor-1 (PAI-1) expression is induced by hypoxia (8%
      O(2)) via the PAI-1 promoter region -175/-159 containing a hypoxia response
      element (HRE-2) binding the hypoxia-inducible factor-1 (HIF-1) and an adjacent
      response element (HRE-1) binding a so far unknown factor. The aim of the present
      study was to identify this factor and to investigate its role in the regulation
      of PAI-1 expression. It was found by supershift assays that the upstream
      stimulatory factor-2a (USF-2a) bound mainly to the HRE-1 of the PAI-1 promoter
      and to a lesser extent to HRE-2. Overexpression of USF-2a inhibited PAI-1
      messenger RNA and protein expression and activated L-type pyruvate kinase
      expression in primary rat hepatocytes under normoxia and hypoxia. Luciferase
      (Luc) gene constructs driven by 766 and 276 base pairs of the 5'-flanking region
      of the PAI-1 gene were transfected into primary hepatocytes together with
      expression vectors encoding wild-type USF-2a and a USF-2a mutant lacking DNA
      binding and dimerization activity (DeltaHU2a). Cotransfection of the wild-type
      USF-2a vector reduced Luc activity by about 8-fold, whereas cotransfection of
      DeltaHU2a did not influence Luc activity. Mutation of the HRE-1 (-175/-168) in
      the PAI-1 promoter Luc constructs decreased USF-dependent inhibition of Luc
      activity. Mutation of the HRE-2 (-165/-158) was less effective. Cotransfection of
      a HIF-1alpha vector could compete for the binding of USF at HRE-2. These results
      indicated that the balance between 2 transcriptional factors, HIF-1 and USF-2a,
      which can bind adjacent HRE sites, appears to be involved in the regulation of
      PAI-1 expression in many clinical conditions.

PMID- 11313256
TI  - Truncated mutant B subunit for factor XIII causes its deficiency due to impaired
      intracellular transportation.
AB  - Two Japanese patients were newly diagnosed as having B subunit (XIIIB) deficiency
      of factor XIII (former type I deficiency). Both patients have a previously
      described one-base deletion at the boundary between intron A/exon II in the XIIIB
      gene, heterozygously or homozygously. A founder effect was proposed for this
      mutation because 3 unrelated patients with XIIIB deficiency also share 2 3'
      polymorphisms. In one patient heterozygous for the above mutation, a novel
      mutation was also identified: a deletion of guanosine in exon IX (delG) of the
      XIIIB gene. To understand the molecular and cellular pathology of the delG
      mutation, expression studies were performed using a cultured mammalian cell line.
      Pulse-chase experiments showed that a resultant truncated XIIIB remained inside
      the cells and could not be secreted into the culture medium. Furthermore,
      immunocytochemical examinations by epifluorescence, confocal, and electron
      microscopes indicated impaired intracellular transportation of the truncated
      XIIIB from the endoplasmic reticulum to the Golgi apparatus. No mutations in the
      gene for the A subunit (XIIIA) were identified in this patient. Therefore,
      secretion of the truncated XIIIB must also be impaired in vivo, leading to a
      secondary XIIIA deficiency. These results support a previous conclusion that
      genetic defects of XIIIB are the basis for the former type I factor XIII
      deficiency.

PMID- 11313257
TI  - The interleukin-13 receptor alpha2 chain: an essential component for binding and
      internalization but not for interleukin-13-induced signal transduction through
      the STAT6 pathway.
AB  - The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains,
      IL-13Ralpha1 (also known as IL-13Ralpha') and IL-13Ralpha2 (also known as IL
      13Ralpha). For a functional IL-13 receptor, the IL-13Ralpha1 chain forms a
      productive complex with the primary IL-4 binding protein (IL-4Ralpha also known
      as IL-4Rbeta). However, the function of the IL-13Ralpha2 chain is not clear even
      though this chain binds IL-13 with high affinity. This study demonstrates that IL
      13Ralpha2 can undergo internalization after binding to ligand without causing
      activation of its signaling pathways. These conclusions were drawn on the basis
      of (1) internalization of (125)I-IL-13 in Chinese hamster ovarian (CHO-K1) and
      T98G glioblastoma cells transiently transfected with the IL-13Ralpha2 chain; (2)
      a recombinant chimeric fusion protein comprising IL-13 and a mutated form of
      Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically
      cytotoxic to IL-13Ralpha2-transfected CHO-K1 cells in a gene dose-dependent
      manner, whereas cells transfected with vector alone were not sensitive; and (3)
      IL-13 did not cause activation of signal transduction and activation of
      transcription 6 (STAT6) in IL-13Ralpha2-transfected cells. IL-13 efficiently
      caused activation of STAT6 protein in cells transfected with the IL-13Ralpha1 and
      IL-4Ralpha chains, and IL-13Ralpha2 inhibited this activation. Taken together,
      these observations indicate that internalization of IL-13Ralpha2 is signal
      independent and that this property of IL-13Ralpha2 can be exploited for receptor
      directed cancer therapy.

PMID- 11313258
TI  - Localization of recombination activating gene 1/green fluorescent protein
      (RAG1/GFP) expression in secondary lymphoid organs after immunization with T
      dependent antigens in rag1/gfp knockin mice.
AB  - Secondary rearrangements of immunoglobulin gene segments that generate a new
      antibody repertoire in peripheral B cells have been described as receptor
      revision and occur by as yet unknown mechanisms. To determine the importance of
      recombination activating gene (RAG) expression in receptor revision, heterozygous
      rag1/green fluorescent protein (gfp) knockin mice were used to examine the
      location of RAG1 expression in the germinal centers (GCs) of lymphoid follicles
      after immunization with a variety of T-cell-dependent antigens. Immunization of
      rag1/gfp heterozygous mice or rag1 homozygous knockout mice reconstituted with
      rag1/gfp heterozygous spleen cells caused the down-regulation of RAG1/GFP signal
      in GCs. Although some RAG1/GFP(+) cells appeared in regions surrounding the
      peanut agglutinin (PNA)(+)GL-7(+) GC area, RAG1/GFP(+) cells did not accumulate
      in the central region. In addition, the stimulation of spleen B cells with anti
      mu antibody plus interleukin-4 (IL-4) or with anti-CD40 monoclonal antibody plus
      IL-7 did not induce GFP signals at detectable levels in vitro. These results
      clearly demonstrate that RAG1 re-expression either does not occur or is at
      extremely low levels in antigen-driven B cells in GCs of secondary lymphoid
      follicles, suggesting that other mechanisms may mediate the gene rearrangements
      observed in receptor revision.

PMID- 11313259
TI  - Missense mutation of the interleukin-12 receptor beta1 chain-encoding gene is
      associated with impaired immunity against Mycobacterium avium complex infection.
AB  - Interleukin-12 (IL-12) plays an important role in the production of interferon
      gamma (IFN-gamma) and is essential for protection against intracellular pathogens
      such as Mycobacterium and Salmonella. A 31-year-old man had disseminated
      Mycobacterium avium complex (MAC) infection. The production of IFN-gamma by
      peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA-PBMCs)
      was found severely impaired (40.7 pg/mL compared with 833 +/- 289 pg/mL for the
      patient's and healthy subjects' (n = 3) PHA- PBMCs, respectively), and the
      patient's PHA-PBMCs completely lacked surface IL-12 receptor beta1 (IL-12Rbeta1)
      chain. The IL-12Rbeta1 gene transcript in his PHA-PBMCs had an R213W substitution
      in each allele. Family history showed that both parents were heterozygotes in the
      R213W substitution. Transfection of a human embryonal kidney cell line 293
      (HEKC293) with wild-type IL-12Rbeta1wt gene led to cell surface IL-12Rbeta1
      expression; however, no expression was seen in HEKC293 transfected with the
      mutated IL-12Rbeta1R213W gene. The IL-12Rbeta1 gene transcript, but no IL
      12Rbeta1 protein, was detected in PHA-PBMCs and T cells, suggesting a post
      translational event(s), most likely a shortened turnover of the protein. The
      R213W substitution was not detected in the cells of 32 healthy persons or of 25
      patients with tuberculosis or MAC infection. Six amino acid substitutions (Q214R,
      M365T, G378R, H438Y, A525T, and G594E) were identified, but the incidences of
      such substitutions were not significantly different between the groups. The Q214R
      substitution is reportedly linked to IL-12Rbeta1 deficiency; however, the study
      showed that 19 and 10 of 57 Japanese and 6 and 4 of 33 healthy white persons were
      heterozygous and homozygous for Arg-214, respectively, suggesting that the Q214R
      substitution represents a polymorphism and is not related to IL-12Rbeta1
      deficiency but that the R213W substitution is responsible for IL-12Rbeta1
      deficiency.

PMID- 11313260
TI  - HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize
      in white pulps and germinal centers from infected patients.
AB  - Human immunodeficiency virus (HIV) infection is characterized by the massive
      infiltration of secondary lymphoid organs with activated CD8(+) T lymphocytes.
      While converging data indicated that these cells were HIV-specific cytotoxic T
      lymphocytes (CTLs) responsible for HIV spread limitation, direct evidence was
      lacking. Here, the presence of HIV-specific effector CTLs was demonstrated
      directly ex vivo in 15 of 24 microdissected splenic white pulps from an untreated
      patient and in 1 of 24 tonsil germinal centers from a second patient with
      incomplete viral suppression following bitherapy. These patients had plasma HIV
      RNA loads of 5900 and 820 copies per milliliter. The frequencies of HIV-1 DNA(+)
      cells in their lymphoid organs were more than 1 in 50 and 1 in 175, respectively.
      Spliced viral messenger RNA (a marker for ongoing viral replication) was present
      in most immunocompetent structures tested. Conversely, CTL activity was not found
      in spleens from 2 patients under highly active antiretroviral therapy, with
      undetectable plasma viral load. These patients had much lower spleen DNA(+) cell
      frequencies (1 in 2700 and 1 in 3800) and no white pulps containing spliced RNA.
      CTL effector activity as well as spliced viral messenger RNA were both
      concentrated in the white pulps and germinal centers. This colocalization
      indicates that viral replication in immunocompetent structures of secondary
      lymphoid organs triggers anti-HIV effector CTLs to these particular locations,
      providing clues to target therapeutic intervention.

PMID- 11313261
TI  - RELT, a new member of the tumor necrosis factor receptor superfamily, is
      selectively expressed in hematopoietic tissues and activates transcription factor
      NF-kappaB.
AB  - The members of tumor necrosis factor receptor (TNFR) superfamily have been
      designated as the "guardians of the immune system" due to their roles in immune
      cell proliferation, differentiation, activation, and death (apoptosis). This
      study reports the cloning of a new member of the TNFR superfamily, RELT (Receptor
      Expressed in Lymphoid Tissues). RELT is a type I transmembrane glycoprotein with
      a cysteine-rich extracellular domain, possessing significant homology to other
      members of the TNFR superfamily, especially TNFRSF19, DR3, OX40, and LTbeta
      receptor. The messenger RNA of RELT is especially abundant in hematologic tissues
      such as spleen, lymph node, and peripheral blood leukocytes as well as in
      leukemias and lymphomas. RELT is able to activate the NF-kappaB pathway and
      selectively binds tumor necrosis factor receptor-associated factor 1. Although
      the soluble form of RELT fusion protein does not inhibit the one-way mixed
      lymphocyte reaction, immobilized RELT is capable of costimulating T-cell
      proliferation in the presence of CD3 signaling. These results define a new member
      of the TNFR superfamily that may be a potential regulator of immune responses.

PMID- 11313262
TI  - Characteristics of early murine B-lymphocyte precursors and their direct
      sensitivity to negative regulators.
AB  - Recently, a collection of surface markers was exploited to isolate viable Lin(-)
      TdT(+) cells from murine bone marrow. These early pro-B cells were enriched for B
      lineage lymphocyte precursor activity measured by short-term culture and had
      little responsiveness to myeloid growth factors. Early precursors can be
      propagated with remarkably high cloning frequencies in stromal cell-free, serum
      free cultures, permitting this analysis of direct regulatory factors. Expression
      of the interleukin-7 receptor (IL-7Ralpha) chain marks functional precursors and
      IL-7 is necessary for progression beyond the CD45RA(+) CD19(-) stage. Efficient
      survival and differentiation were only observed when stem cell factor and Flt-3
      ligand were also present. IL-7-responsive CD19(+) precursors are estrogen
      resistant. However, B-lineage differentiation was selectively abrogated when
      highly purified Lin(-) precursors were treated with hormone in the absence of
      stromal cells. In addition, early stages of B lymphopoiesis were arrested by
      limitin, a new interferon (IFN)-like cytokine as well as IFN-alpha, IFN-gamma, or
      transforming growth factor beta (TGF-beta), but not by epidermal growth factor
      (EGF). Lin(-) TdT(+) early pro-B cells are shown here to be CD27(+) AA4.1(+/-)Ki
      67(+) Ly-6C(-) Ly-6A/Sca-1(Lo/-)Thy-1(-)CD43(+) CD4(+/-)CD16/32(Lo/-)CD44(Hi) and
      similar in some respects to the "common lymphoid progenitors" (CLP) identified by
      others. Although early pro-B cells have lost myeloid differentiation potential,
      transplantation experiments described here reveal that at least some can generate
      T lymphocytes. Of particular importance is the demonstration that a pivotal early
      stage of lymphopoiesis is directly sensitive to negative regulation by hormones
      and cytokines.

PMID- 11313263
TI  - Immunoglobulin heavy-chain gene rearrangement in adult acute lymphoblastic
      leukemia reveals preferential usage of J(H)-proximal variable gene segments.
AB  - The aim of this study was to characterize individual-segment and overall patterns
      of V(H) gene usage in adult B-lineage acute lymphoblastic leukemia (ALL).
      Theoretical values of V(H) segment usage were calculated with the assumption that
      all V(H) segments capable of undergoing rearrangement have an equal probability
      of selection for recombination. Leukemic clones from 127 patients with adult B
      lineage acute leukemias were studied by fingerprinting by means of primers for
      the framework 1 and joining segments. Clones from early preimmune B cells (245
      alleles identified) show a predominance of V(H)6 family rearrangements and,
      consequently, do not conform to this hypothesis. However, profiles of V(H) gene
      family usage in mature B cells, as investigated in peripheral blood (6 samples),
      B-cell lymphomas (36 clones) and chronic lymphocytic leukemia (56 clones), are in
      agreement with this theoretical profile. Sequence analyses of 64 V(H) clones in
      adult ALL revealed that the rate of V(H) usage is proportional to the proximity
      of the V(H) gene to the J(H) locus and that the relationship can be
      mathematically defined. Except for V(H)6, no other V(H) gene is excessively used
      in adult ALL. V(H) pseudogenes are rarely used (n = 2), which implies the
      existence of early mechanisms in the pathway to B-cell maturation to reduce
      wasteful V(H)-(D(H))-J(H) recombination. Finally, similar to early immunoglobulin
      H rearrangement patterns in the mouse, B cells of ALL derive from a pool of cells
      more immature than the cells in chronic lymphoid B-cell malignancies.

PMID- 11313264
TI  - Fever-range hyperthermia dynamically regulates lymphocyte delivery to high
      endothelial venules.
AB  - Fever is associated with increased survival during acute infection, although its
      mechanism of action is largely unknown. This study found evidence of an
      unexpectedly integrated mechanism by which fever-range temperatures stimulate
      lymphocyte homing to secondary lymphoid tissues by increasing L-selectin and
      alpha4beta7 integrin-dependent adhesive interactions between circulating
      lymphocytes and specialized high endothelial venules (HEV). Exposure of splenic
      lymphocytes in vivo to fever-like whole-body hyperthermia (WBH; 39.8 +/- 0.2
      degrees C for 6 hours) stimulated both L-selectin and alpha4beta7 integrin
      dependent adhesion of lymphocytes to HEV under shear conditions in lymph nodes
      and Peyer patches. The adhesiveness of HEV ligands for L-selectin and alpha4beta7
      integrin (ie, peripheral lymph node addressin and mucosal addressin cell adhesion
      molecule-1) also increased during WBH or febrile responses associated with
      lipopolysaccharide-induced or turpentine-induced inflammation. Similar increases
      in HEV adhesion occurred during hyperthermia treatment of lymph node and Peyer
      patch organ cultures in vitro, indicating that the local lymphoid tissue
      microenvironment is sufficient for the hyperthermia response. In contrast, WBH
      did not augment adhesion in squamous endothelium of nonlymphoid tissues. Analysis
      of homing of alpha4beta7(hi) L-selectin(lo) murine TK1 cells and L-selectin(hi)
      alpha4beta7 integrin-negative 300.19/L-selectin transfectant cells showed that
      fever-range temperatures caused a 3- to 4-fold increase in L-selectin and
      alpha4beta7 integrin-dependent trafficking to secondary lymphoid tissues. Thus,
      enhanced lymphocyte delivery to HEV by febrile temperatures through bimodal
      regulation of lymphocyte and endothelial adhesion provides a novel mechanism to
      promote immune surveillance.

PMID- 11313265
TI  - Iron transport in a lymphoid cell line with the hemochromatosis C282Y mutation.
AB  - The gene for hemochromatosis (HFE) is expressed in a variety of cells, including
      those not thought to be affected by this disease. The impact of HFE on iron
      transport was examined in B-lymphoid cell lines developed from a patient with
      hemochromatosis with the HFE C282Y mutation (C282Y cells) and an individual with
      the wild-type HFE gene (WT cells). Whereas both cell lines expressed HFE protein,
      C282Y cells displayed less HFE protein at the cell surface. Transferrin receptor
      (TfR) number was 2- to 3-fold greater in WT cells than in C282Y cells, while TfR
      affinity for transferrin (Tf) was slightly lower in C282Y cells. TfR distribution
      between intracellular and cell-surface compartments was similar in both cell
      lines. Iron uptake per cell was greater in WT cells but was not increased
      proportional to TfR number. When considered relative to cell-surface TfR number,
      however, iron uptake and Tf internalization were actually greater in C282Y cells.
      Surprisingly, Tf-independent iron uptake was also significantly greater in C282Y
      cells than in WT cells. The ferritin content of C282Y cells was approximately 40%
      that of WT cells. Exposure of cells to pro-oxidant conditions in culture led to a
      greater inhibition of proliferation in C282Y cells than in WT cells. Our results
      indicate that in this B-lymphoid cell line, the HFE C282Y mutation affects both
      Tf-dependent and -independent iron uptake and enhances cell sensitivity to
      oxidative stress. The role of HFE in iron uptake by B cells may extend beyond its
      known interaction with the TfR.

PMID- 11313266
TI  - Signal-regulatory protein alpha (SIRPalpha) but not SIRPbeta is involved in T
      cell activation, binds to CD47 with high affinity, and is expressed on immature
      CD34(+)CD38(-) hematopoietic cells.
AB  - Signal-regulatory proteins (SIRPs) represent a new family of
      inhibitory/activating receptor pairs. They consist of 3 highly homologous
      immunoglobulin (Ig)-like domains in their extracellular regions, but differ in
      their cytoplasmic regions by the presence (SIRPalpha) or absence (SIRPbeta) of
      immunoreceptor tyrosine-based inhibitory motifs (ITIMs). To analyze the
      differential expression on hematopoietic cells, function and ligand binding
      capacity of SIRPalpha and SIRPbeta molecules, soluble fusion proteins consisting
      of the extracellular domains of SIRPalpha1, SIRPalpha2, and SIRPbeta1, as well as
      SIRPalpha/beta-specific and SIRPbeta-specific monoclonal antibodies (MoAbs) were
      generated. In contrast to SIRPalpha1 and SIRPalpha2, no adhesion of SIRPbeta1 to
      CD47 could be detected by cell attachment assays and flow cytometry. Using
      deletion constructs of SIRPalpha1, the epitope responsible for SIRPalpha1 binding
      to CD47 could be confined to the N-terminal Ig-like loop. Flow cytometry analysis
      with SIRPalpha/beta- and SIRPbeta-specific MoAbs revealed that SIRPalpha but not
      SIRPbeta is expressed on CD34(+)CD38(-) hematopoietic cells. In addition, a
      strong SIRPalpha expression was also observed on primary myeloid dendritic cells
      (DCs) from peripheral blood as well as on in vitro generated DCs. Analysis of the
      T-cell stimulatory capacity of in vitro generated DCs in the presence of soluble
      SIRPalpha1 fusion proteins as well as SIRPalpha/beta-specific and CD47-specific
      MoAbs revealed a significant reduction of T-cell proliferation in mixed
      lymphocyte reaction and inhibition of induction of primary T-cell responses under
      these conditions. In contrast, soluble SIRPalpha or SIRPbeta-specific antibodies
      had no effect. The data suggest that the interaction of SIRPalpha with CD47 plays
      an important role during T-cell activation and induction of antigen-specific
      cytotoxic T-lymphocyte responses by DCs.

PMID- 11313267
TI  - Long-term induction of immune tolerance after blockade of CD40-CD40L interaction
      in a mouse model of hemophilia A.
AB  - A factor VIII-deficient knockout mouse was used as a model for severe hemophilia
      A to characterize the immune response to recombinant human factor VIII (fVIII)
      and to study new approaches for induction of immune tolerance to fVIII. Mice
      initially received periodic injections of fVIII in doses similar to those used
      for the treatment of human hemophilia A. To induce immune tolerance, a hamster
      monoclonal antibody specific for murine CD40 ligand (CD40L or CD154) was injected
      with fVIII. Control mice received fVIII alone or fVIII and hamster immunoglobulin
      G. After treatment, humoral and cellular immune responses were evaluated. Ninety
      five percent of anti-CD40L-treated mice had lower titers of anti-fVIII antibody
      (less than 1 microg/mL) compared with fVIII-injected control mice (mean, 18
      microg/mL). To determine whether anti-CD40L treatment induces long-term immune
      tolerance, mice were rechallenged 3 times with fVIII alone. At 150 days after
      treatment, 12 of 22 anti-CD40L-treated mice remained tolerant to fVIII (anti
      fVIII antibody titers less than 1 microg/mL). However, tolerant mice immunized
      with tetanus toxoid (TT) developed high anti-TT antibody, demonstrating that
      tolerance is fVIII specific. T cells from tolerant mice showed impaired
      proliferative responses after stimulation with fVIII in vitro and lack of
      production of the cytokines interleukin-2 (IL-2), IL-4, interferon gamma, and IL
      10. These results demonstrate that long-term immune tolerance to fVIII was
      effectively induced after early blockade of CD40-CD40L interaction. In addition,
      the lack of tolerance in this model was associated with the expression of a Th2
      phenotype.

PMID- 11313268
TI  - Interleukin-11 induces Th2 polarization of human CD4(+) T cells.
AB  - Exploration of the immunomodulatory activities of the multifunctional cytokine
      interleukin-11 (IL-11) has prompted several therapeutic applications. The
      immunomodulatory effects of IL-11 on human antigen-presenting cells and on T
      cells were investigated. IL-11 inhibited IL-12 production by activated CD14(+)
      monocytes, but not by mature dendritic cells (DCs) stimulated via CD40 ligation.
      Moreover, IL-11 did not affect either DC maturation, as demonstrated by
      phenotypic analysis and evaluation of cytokine production, or DC generation from
      progenitor cells in the presence of specific growth factors. Molecular analysis
      demonstrated the expression of IL-11 receptor messenger RNA in highly purified
      CD14(+) monocytes, CD19(+) B cells, CD8(+), and CD4(+) T cells, and
      CD4(+)CD45RA(+) naive T lymphocytes. In keeping with this finding, IL-11 directly
      prevented Th1 polarization of highly purified CD4(+)CD45RA(+) naive T cells
      stimulated with anti-CD3/CD28 antibodies, as demonstrated by significant
      increases of IL-4 and IL-5, by significantly decreased interferon-gamma
      production and by flow cytometry intracellular staining of cytokines.
      Coincubation of naive T cells with DCs, the most potent stimulators of Th1
      differentiation, did not revert IL-11-mediated Th2 polarization. Furthermore,
      parallel experiments demonstrated that the activity of IL-11 was comparable with
      that induced by IL-4, the most effective Th2-polarizing cytokine. Taken together,
      these findings show that IL-11 inhibits Th1 polarization by exerting a direct
      effect on human T lymphocytes and by reducing IL-12 production by macrophages.
      Conversely, IL-11 does not exert any activity on DCs. This suggests that IL-11
      could have therapeutic potential for diseases where Th1 responses play a dominant
      pathogenic role.

PMID- 11313269
TI  - Stimulation of autologous proliferative and cytotoxic T-cell responses by
      "leukemic dendritic cells" derived from blast cells in acute myeloid leukemia.
AB  - Effective presentation of tumor antigens is fundamental to strategies aimed at
      enrolling the immune system in eradication of residual disease after conventional
      treatments. Myeloid malignancies provide a unique opportunity to derive dendritic
      cells (DCs), functioning antigen-presenting cells, from the malignant cells
      themselves. These may then co-express leukemic antigens together with appropriate
      secondary signals and be used to generate a specific, antileukemic immune
      response. In this study, blasts from 40 patients with acute myeloid leukemia
      (AML) were cultured with combinations of granulocyte-macrophage colony
      stimulating factor, interleukin 4, and tumor necrosis factor alpha, and
      development to DCs was assessed. After culture, cells from 24 samples exhibited
      morphological and immunophenotypic features of DCs, including expression of major
      histocompatibility complex class II, CD1a, CD83, and CD86, and were potent
      stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of
      autologous T-cell responses was assessed by the proliferative response of
      autologous T cells to the leukemic DCs and by demonstration of the induction of
      specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective
      stimulators in the autologous MLR, and low, but consistent, autologous,
      antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%
      37%). This study indicates that cells with enhanced antigen-presenting ability
      can be generated from AML blasts, that these cells can effectively prime
      autologous cytotoxic T cells in vitro, and that they may be used as potential
      vaccines in the immunotherapy of AML.

PMID- 11313270
TI  - Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase
      activity can cause either T-B-severe combined immune deficiency or Omenn
      syndrome.
AB  - Omenn syndrome (OS) is an inherited disorder characterized by an absence of
      circulating B cells and an infiltration of the skin and the intestine by
      activated oligoclonal T lymphocytes, indicating that a profound defect in the
      lymphoid developmental program could be accountable for this condition. Inherited
      mutations in either the recombination activating genes RAG1 or RAG2, resulting in
      partial V(D)J recombinase activity, were shown to be responsible for OS. This
      study reports on the characterization of new RAG1/2 gene mutations in a series of
      9 patients with OS. Given the occurrence of the same mutations in patients with T
      B-severe combined immune deficiency or OS on 3 separate occasions, the proposal
      is made that an additional factor may be required in certain circumstances for
      the development of the Omenn phenotype. The nature of this factor is discussed.

PMID- 11313271
TI  - Survivin is expressed on CD40 stimulation and interfaces proliferation and
      apoptosis in B-cell chronic lymphocytic leukemia.
AB  - In B-cell chronic lymphocytic leukemia (B-CLL), defective apoptosis causes the
      accumulation of mature CD5(+) B cells in lymphoid organs, bone marrow (BM), and
      peripheral blood (PB). These cells are the progeny of a proliferating pool that
      feeds the accumulating compartment. The authors sought to determine which
      molecular mechanisms govern the proliferating pool, how they relate to apoptosis,
      and what the role is of the microenvironment. To begin to resolve these problems,
      the expression and modulation of the family of inhibitor of apoptosis proteins
      (IAPs) were investigated, with consideration given to the possibility that
      physiological stimuli, such as CD40 ligand (CD40L), available to B cells in the
      microenvironment, might modulate IAP expression. The in vitro data on mononuclear
      cells from PB or BM of 30 patients demonstrate that B-CLL cells on CD40
      stimulation express Survivin and that Survivin is the only IAP whose expression
      is induced by CD40L. Through immunohistochemistry, in vivo Survivin expression in
      lymph node (LN) and BM biopsies was evaluated. In reactive LN, Survivin was
      detected only in highly proliferating germinal center cells. In LN from patients
      with B-CLL, Survivin was detected only in pseudofollicles. Pseudofollicle
      Survivin(+) cells were actively proliferating and, in contrast to Survivin(+) B
      cells found in normal GC, were Bcl-2(+). In B-CLL BM biopsies, CD5(+),
      Survivin(+) cells were observed in clusters interspersed with T cells. These
      findings establish that Survivin controls the B-CLL proliferative pool
      interfacing apoptosis and that its expression may be modulated by
      microenvironmental stimuli.

PMID- 11313272
TI  - Cytokine-regulated expression of survivin in myeloid leukemia.
AB  - Survivin, a member of the inhibitors-of-apoptosis gene family, is expressed in a
      cell-cycle-dependent manner in all the most common cancers but not in normal
      differentiated adult tissues. Survivin expression and regulation were examined in
      acute myeloid leukemia (AML). Survivin was detected by Western blot analysis in
      all myeloid leukemia cell lines and in 16 of 18 primary AML samples tested. In
      contrast, normal CD34(+) cells and normal peripheral blood mononuclear cells
      expressed no or very low levels of survivin. Cytokine stimulation increased
      survivin expression in leukemic cell lines and in primary AML samples. In
      cultured primary samples, single-cytokine stimulation substantially increased
      survivin expression in comparison with control cells, and the combination of G
      CSF, GM-CSF, and SCF increased survivin levels even further. Conversely, all
      trans retinoic acid significantly decreased survivin protein levels in HL-60, OCI
      AML3, and NB-4 cells within 96 hours, parallel to the induction of myelomonocytic
      differentiation. Using selective pharmacologic inhibitors, the differential
      involvement of mitogen-activated protein kinase kinase (MEK) and
      phosphatidylinositol-3 kinase (PI3K) pathways were demonstrated in the regulation
      of survivin expression. The MEK inhibitor PD98059 down-regulated survivin
      expression in both resting and GM-CSF-stimulated OCI-AML3 cells, whereas the PI3K
      inhibitor LY294002 inhibited survivin expression only on GM-CSF stimulation. In
      conclusion, these results demonstrate that survivin is highly expressed and
      cytokine-regulated in myeloid leukemias and suggest that hematopoietic cytokines
      exert their antiapoptotic and mitogenic effects, at least in part, by increasing
      survivin levels.

PMID- 11313273
TI  - Autocrine cell suicide in a Burkitt lymphoma cell line (Daudi) induced by
      interferon alpha: involvement of tumor necrosis factor as ligand for the CD95
      receptor.
AB  - The CD95 receptor, a member of the tumor necrosis factor (TNF) receptor
      superfamily, mediates signals for cell death on specific ligand or antibody
      engagement. It was hypothesized that interferon alpha (IFN-alpha) induces
      apoptosis through activation of the CD95-mediated pathway and that CD95 and
      ligands of the death domain may belong to the group of IFN-stimulated genes.
      Therefore, the effect of IFN-alpha on CD95-CD95L expression, on the release of
      TNF-alpha, and on TNF receptor 1 expression in an IFN-sensitive human Burkitt
      lymphoma cell line (Daudi) was investigated. After 5 days' incubation, apoptosis
      in 81% of IFN-alpha-treated Daudi cells was preceded by a release of TNF-alpha
      and an induction of CD95 receptor expression. Although supernatants of IFN
      treated Daudi cells induced apoptosis of CD95-sensitive Jurkat cells, CD95L was
      undetectable on protein or on messenger RNA levels, and the weak initial
      expression of TNF receptor 1 increased only slightly during IFN treatment.
      Surprisingly, binding of TNF-alpha to CD95 was observed and confirmed by 3
      different techniques-enzyme-linked immunosorbent assay using immobilized CD95:Fc
      immunoglobulin G, immunoprecipitation assay using CD95 receptor precipitates of
      Daudi cells, and binding of sodium iodide 125-TNF-alpha to Daudi cells, which was
      strongly stimulated by IFN-alpha and inhibited by CD95L, CD95:Fc, unlabeled TNF
      alpha, and anti-TNF-alpha antibody. Preincubation of Daudi cells with antagonists
      of the CD95-mediated pathway resulted in an inhibition of IFN-alpha-mediated cell
      death. The present investigation shows that IFN-alpha induces autocrine cell
      suicide of Daudi cells by a cross-talk between the CD95 receptor and TNF-alpha.
      The CD95 receptor can be considered a third TNF receptor, in addition to p55 and
      p75.

PMID- 11313274
TI  - Constitutive NF-kappaB maintains high expression of a characteristic gene
      network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed
      Sternberg cells.
AB  - Constitutively activated nuclear factor (NF)-kappaB is observed in a variety of
      neoplastic diseases and is a hallmark of the malignant Hodgkin and Reed-Sternberg
      cells (H/RS) in Hodgkin lymphoma. Given the distinctive role of constitutive NF
      kappaB for H/RS cell viability, NF-kappaB-dependent target genes were searched
      for by using adenoviral expression of the super-repressor IkappaBDeltaN. A
      surprisingly small but characteristic set of genes, including the cell-cycle
      regulatory protein cyclin D2, the antiapoptotic proteins Bfl-1/A1, c-IAP2, TRAF1,
      and Bcl-x(L), and the cell surface receptors CD86 and CD40 were identified. Thus,
      constitutive NF-kappaB activity maintains expression of a network of genes, which
      are known for frequent, marker-like expression in primary or cultured H/RS cells.
      Intriguingly, CD40, which is able to activate CD86 or Bcl-x(L) via NF-kappaB, is
      itself transcriptionally regulated by NF-kappaB through a promoter proximal
      binding site. NF-kappaB inhibition resulted in massive spontaneous and p53
      independent apoptosis, which could be rescued by ectopic expression of Bcl-x(L),
      underscoring its dominant role in survival of H/RS cells. Hence, NF-kappaB
      controls a signaling network in H/RS cells, which promotes tumor cell growth and
      confers resistance to apoptosis.

PMID- 11313275
TI  - Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a
      single cell level.
AB  - Antigen-presenting cells (APCs) from subcutaneous mouse MOPC315 plasmacytoma
      phagocytosed immunoglobulin G-coated magnetic beads, enabling efficient isolation
      within 2 hours by magnetic separation (APC-MB). Cell morphology was
      heterogeneous, with some of the cells having dendrites. The surface phenotype of
      purified tumor APCs-MB was CD11b(+), CD11c(+), CD40(+), CD80(+), CD86(+), and MHC
      class II(+). Tumor APCs-MB expressed messenger RNA for fractalkine and ABCD-1
      chemokines, and for CC-type chemokine receptors CCR5 and CCR7, indicating the
      presence of mature dendritic cells (DCs). Visualized at a single cell level
      within 4 hours after disruption of the tumor, APCs-MB induced rapid Ca(++)
      mobilization in MHC class II-restricted tumor idiotype (Id)-specific cloned
      CD4(+) T cells. In long-term assays, tumor APCs-MB induced proliferation of naive
      T cells from Id-specific T-cell receptor transgenic mice. The results suggest
      that tumor APCs-MB represent a heterogeneous cell population that includes
      myeloid-derived DCs of various stages of maturation. A considerable fraction (>
      or = 15%) of DCs is spontaneously primed with tumor-specific antigen.

PMID- 11313276
TI  - The corepressor CtBP interacts with Evi-1 to repress transforming growth factor
      beta signaling.
AB  - Evi-1 is a zinc finger nuclear protein whose inappropriate expression leads to
      leukemic transformation of hematopoietic cells in mice and humans. This was
      previously shown to block the antiproliferative effect of transforming growth
      factor beta (TGF-beta). Evi-1 represses TGF-beta signaling by direct interaction
      with Smad3 through its first zinc finger motif. Here, it is demonstrated that Evi
      1 represses Smad-induced transcription by recruiting C-terminal binding protein
      (CtBP) as a corepressor. Evi-1 associates with CtBP1 through one of the consensus
      binding motifs, and this association is required for efficient inhibition of TGF
      beta signaling. A specific inhibitor for histone deacetylase (HDAc) alleviates
      Evi-1-mediated repression of TGF-beta signaling, suggesting that HDAc is involved
      in the transcriptional repression by Evi-1. This identifies a novel function of
      Evi-1 as a member of corepressor complexes and suggests that aberrant recruitment
      of corepressors is one of the mechanisms for Evi-1-induced leukemogenesis.

PMID- 11313277
TI  - Methylation profiling in acute myeloid leukemia.
AB  - Aberrant methylation of multiple CpG islands has been described in acute myeloid
      leukemia (AML), but it is not known whether these are independent events or
      whether they reflect specific methylation defects in a subset of cases. To study
      this issue, the methylation status of 14 promoter-associated CpG islands was
      analyzed in 36 cases of AML previously characterized for estrogen-receptor
      methylation (ERM). Cases with methylation density of 10% or greater were
      considered positive. Seventeen cases (47%) were ERM(+) while 19 cases were ERM(
      ). Hypermethylation of any of the following, p15, p16, CACNA1G, MINT1, MINT2,
      MDR1, THBS1, and PTC1 (2 promoters), was relatively infrequent (6% to 31% of
      patients). For each of these CpG islands, the methylation density was positively
      correlated with ERM density (rank order correlation coefficients, 0.32-0.59; 2
      tailed P < or = .058 for each gene). Hypermethylation of MYOD1, PITX2, GPR37, and
      SDC4 was frequently found in AML (47% to 64% of patients). For each of these
      genes as well, methylation density was positively correlated with ERM density
      (correlation coefficients 0.43 to 0.69, P < or = .0087 for each gene). MLH1 was
      unmethylated in all cases. Hypermethylation of p15, MDR1, and SDC4 correlated
      with reduced levels of expression. There was an inverse correlation between age
      and the number of genes methylated (P = .0030). It was concluded that CpG-island
      methylation in AML results from methylation defects in subsets of cases. These
      results have potential implications for the classification and prognosis of AML
      and for the identification of patients who may benefit from treatment with
      methylation inhibitors.

PMID- 11313278
TI  - Regulation of the nuclear proteasome activity in myelomonocytic human leukemia
      cells after adriamycin treatment.
AB  - Treatment of different human leukemia cell variants with the anthracycline
      adriamycin was associated with a rapid activation of the proteasome. Thus,
      proliferating U937, TUR, and retrodifferentiated U937 cells exhibited a 4.3-fold,
      5.8-fold, and 4.3-fold proteasome activation within 15 minutes after adriamycin
      treatment, respectively. In contrast, little if any proteasome activation was
      detectable in a growth-arrested differentiated U937 population following
      adriamycin treatment. Further analysis of this mechanism revealed a significant
      reduction of adriamycin-induced proteasome activity after inhibition of poly(ADP
      ribose) polymerase (PARP) by 3-aminobenzamide (3-ABA) in the proliferating
      leukemic cell types. These findings suggested that PARP is involved in the
      regulation of drug-induced proteasome activation. Indeed, anti-PARP
      immunoprecipitation experiments of adriamycin-treated cells revealed increasing
      levels of coprecipitated, enzymatically active proteasome particularly in the
      proliferating cell variants in contrast to the differentiated U937 cells, with a
      maximum after 15 minutes, and sensitivity to PARP inhibition by 3-ABA. The
      specific role of the PARP was investigated in U937 and TUR cell clones stably
      transfected with a constitutively active antisense PARP (asPARP) vector. Thus,
      asPARP-TUR cells developed a 25-fold increased sensitivity to adriamycin
      treatment. Furthermore, we investigated leukemic blasts isolated from acute
      myelogenous leukemia patients and obtained a similarly enhanced proteasome
      activity after adriamycin treatment, which was dependent on the PARP and thus
      could be coprecipitated with anti-PARP antibodies. Transient transfection of
      leukemic blasts with the asPARP vector significantly reduced the adriamycin
      induced proteasome activation. These data suggest that the PARP-associated
      nuclear proteasome activation represents a potential target within
      chemotherapeutic defense mechanisms developed by leukemia cells.

PMID- 11313279
TI  - Oxidative DNA base modifications in peripheral blood mononuclear cells of
      patients treated with high-dose infusional doxorubicin.
AB  - In prior studies, it was demonstrated that the redox metabolism of doxorubicin
      leads to the formation of promutagenic oxidized DNA bases in human chromatin,
      suggesting a potential mechanism for doxorubicin-related second malignancies. To
      determine whether a similar type of DNA damage is produced in the clinic,
      peripheral blood mononuclear cell DNA from 15 women treated with infusional
      doxorubicin (165 mg/m(2)) as a single agent was examined for 14 modified bases by
      gas chromatography/mass spectrometry with selected ion monitoring. Prior to the
      96-hour doxorubicin infusion, 13 different oxidized bases were present in all DNA
      samples examined. Chemotherapy, producing a steady-state level of 0.1 microM
      doxorubicin, increased DNA base oxidation up to 4-fold compared to baseline
      values for 9 of the 13 bases studied. Maximal base oxidation was observed 72 to
      96 hours after doxorubicin treatment was begun; the greatest significant
      increases were found for Thy Gly (4.2-fold), 5-OH-Hyd (2.5-fold), FapyAde (2.4
      fold), and 5-OH-MeUra (2.4-fold). The level of the promutagenic base FapyGua
      increased 1.6-fold (P < .02), whereas no change in 8-OH-Gua levels was observed
      in peripheral blood mononuclear cell DNA during the doxorubicin infusion. These
      results suggest that DNA base damage similar to that produced by ionizing
      radiation occurs under clinical conditions in hematopoietic cells after
      doxorubicin exposure. If doxorubicin-induced DNA base oxidation occurs in
      primitive hematopoietic precursors, these lesions could contribute to the
      mutagenic or toxic effects of the anthracyclines on the bone marrow.

PMID- 11313281
TI  - Identification of novel chemoattractant peptides for human leukocytes.
AB  - Superoxide is the most important armory on the primary defense line of monocytes
      against invading pathogens, and the identification of new stimuli and the
      characterization of the regulatory mechanism of superoxide generation are of
      paramount importance. In this study, we identified 3 novel peptides by screening
      a synthetic hexapeptide combinatorial library and modification of 1 of the
      peptides. The isolated peptides that can induce superoxide generation in human
      monocytes are His-Phe-Tyr-Leu-Pro-Met-CONH(2) (HFYLPM), Met-Phe-Tyr-Leu-Pro-Met
      CONH(2) (MFYLPM), and His-Phe-Tyr-Leu-Pro-D-Met-CONH(2) (HFYLPm). All 3 peptides
      also caused intracellular calcium ([Ca(++)](i)) rise. We tested the specificities
      of the peptides on cells of different origin by looking at [Ca(++)](i) rise. All
      3 peptides acted specifically on leukocytes and not on nonimmune cells. Among
      leukocytes, HL60 and Jurkat T cells were stimulated specifically by MFYLPM or
      HFYLPM, respectively. As a physiologic characteristic of the peptides, we
      observed that all 3 peptides induced chemotactic migration of monocytes. Studying
      receptor specificity, we concluded that the 3 peptides might act on some shared
      and some distinct receptor(s) on leukocytes. Studying intracellular signaling set
      in motion by the peptides revealed that HFYLPM, but not MFYLPM or HFYLPm, induced
      chemotaxis via phosphatidylinositol-3 kinase and protein kinase C. Because
      HFYLPM, MFYLPM, and HFYLPm not only exhibit different specificities depending on
      cell type and status of differentiation but also stimulate cells via distinct
      receptors and signaling, the 3 novel peptides might be useful tools to study
      leukocyte activation.

PMID- 11313280
TI  - Down-regulation of interleukin-3/granulocyte-macrophage colony-stimulating factor
      receptor beta-chain in BCR-ABL(+) human leukemic cells: association with loss of
      cytokine-mediated Stat-5 activation and protection from apoptosis after BCR-ABL
      inhibition.
AB  - Several signaling cascades are engaged by expression of the p210 bcr-abl tyrosine
      kinase, and evidence suggests that these signals drive leukemogenesis. In this
      report, signaling pathways were examined and compared between cells derived from
      leukemic patients and cells expressing a bcr-abl construct (MBA). The effects of
      acute inhibition of bcr-abl with STI-571 on these signals and the survival of bcr
      abl-expressing cells were also evaluated. Expression of bcr-abl in interleukin-3
      (IL-3)/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent Mo7e
      cells (MBA) resulted in growth factor independence, constitutive activation of
      Stat-5 phosphorylation, engagement of mitogen-activated protein (MAP) kinase
      signals, and increased expression of PTP1B and bcl-x(L). STI-571 inhibited cell
      growth and induced apoptosis in bcr-abl-expressing cells (MBA, K562, BV-173,
      KBM5) but not in bcr-abl(-) tumor cells (Mo7e, KG-1, ME-180, Daudi). STI-571
      mediated apoptosis correlated with the inhibition of Stat-5 and MAP kinase
      activation and a reduction in overexpressed bcl-x(L) but not in PTP1B. Inhibitor
      had no effect on IL-3/GM-CSF-dependent Mo7e cell signaling and did not prevent
      activation of the other Jak/Stat pathways (interferon alpha, IL-3/GM-CSF).
      However, neither IL-3 nor GM-CSF could reactivate Stat-5 after the STI-571
      mediated inhibition of bcr-abl. Expression of the common beta-chain of the IL
      3/GM-CSF receptor was down-regulated in Stat-5-activated myeloid leukemic cells,
      suppressing IL-3/GM-CSF signal transduction and the ability of these cytokines to
      provide apoptotic protection. These studies suggest that bcr-abl activates
      cytokine-independent mechanisms of survival while inactivating intrinsic cytokine
      signaling cascades, making bcr-abl(+) myeloid cells vulnerable to apoptosis after
      bcr-abl inactivation.

PMID- 11313282
TI  - Repression of ferritin expression increases the labile iron pool, oxidative
      stress, and short-term growth of human erythroleukemia cells.
AB  - The role of ferritin expression on the labile iron pool of cells and its
      implications for the control of cell proliferation were assessed. Antisense
      oligodeoxynucleotides were used as tools for modulating the expression of heavy
      and light ferritin subunits of K562 cells. mRNA and protein levels of each
      subunit were markedly reduced by 2-day treatment with antisense probes against
      the respective subunit. Although the combined action of antisense probes against
      both subunits reduced their protein expression, antisense repression of one
      subunit led to an increased protein expression of the other. Antisense treatment
      led to a rise in the steady-state labile iron pool, a rise in the production of
      reactive oxygen species after pro-oxidative challenges and in protein oxidation,
      and the down-regulation of transferrin receptors. When compared to the repression
      of individual subunits, co-repression of each subunit evoked a more than additive
      increase in the labile iron pool and the extent of protein oxidation. These
      treatments had no detectable effects on the long-term growth of cells. However,
      repression of ferritin synthesis facilitated the renewal of growth and the
      proliferation of cells pre-arrested at the G(1)/S phase. Renewed cell growth was
      significantly less dependent on external iron supply when ferritin synthesis was
      repressed and its degradation inhibited by lysosomal antiproteases. This study
      provides experimental evidence that links the effect of ferritin repression on
      growth stimulation to the expansion of the labile iron pool.

PMID- 11313283
TI  - Glycophorin A dimerization and band 3 interaction during erythroid membrane
      biogenesis: in vivo studies in human glycophorin A transgenic mice.
AB  - Band 3 and glycophorin A (GPA) are the 2 most abundant integral proteins in the
      human erythrocyte membrane. Earlier studies suggested that the 2 proteins may
      associate not only in the mature erythrocyte membrane, but also during their
      posttranslational processing and intracellular trafficking. The purpose of this
      study was to directly examine the GPA-band 3 interaction in vivo and determine
      the nature of this association during erythroid membrane biogenesis. Transgenic
      mice were generated expressing the human glycophorin A gene and were used to
      examine how the induction of human GPA expression affected the levels of murine
      GPA and band 3 expression in the red cell membrane. Murine GPA expression was
      reduced in erythrocytes expressing human GPA, whereas the level of band 3
      expression remained constant, implying a tight coupling of band 3 and GPA
      expression in the membrane of mature red cells. In vivo GPA dimerization was not
      modulated solely by the GPA transmembrane motif, but the distance between this
      motif and the basic residues on the cytoplasmic side of the transmembrane domain
      may also be important. In addition, GPA monomers with varying degrees of
      glycosylation dimerized, providing clear evidence that carbohydrate structures on
      the extracellular domain do not affect dimerization. The association between the
      multiple transmembrane-spanning protein, band 3, and the single transmembrane
      spanning sialoglycoprotein, GPA, may serve as a model for interactions of other
      multi-pass and single-pass polypeptides during membrane biogenesis.

PMID- 11313284
TI  - Molecular identification of Knops blood group polymorphisms found in long
      homologous region D of complement receptor 1.
AB  - Complement receptor 1 (CR1) has been implicated in rosetting of uninfected red
      blood cells to Plasmodium falciparum-infected cells, and rosette formation is
      associated with severe malaria. The Knops blood group (KN) is located on CR1 and
      some of these antigens, ie, McCoy (McC) and Swain-Langley (Sl(a)), show marked
      frequency differences between Caucasians and Africans. Thus, defining the
      molecular basis of these antigens may provide new insight into the mechanisms of
      P falciparum malaria. Monoclonal antibody epitope mapping and serologic
      inhibition studies using CR1 deletion constructs localized McC and Sl(a) to long
      homologous repeat D of CR1. Direct DNA sequencing of selected donors identified
      several single nucleotide polymorphisms in exon 29 coding for complement control
      protein modules 24 and 25. Two of these appeared to be blood group specific: McC
      associated with K1590E and Sl(a) with R1601G. These associations were confirmed
      by inhibition studies using allele-specific mutants. A sequence-specific
      oligonucleotide probe hybridization assay was developed to genotype several
      African populations and perform family inheritance studies. Concordance between
      the 1590 mutation and McC was 94%; that between Sl(a) and 1601 was 88%. All but 2
      samples exhibiting discrepancies between the genotype and phenotype were found to
      be due to low red cell CR1 copy numbers, low or absent expression of some
      alleles, or heterozygosity combined with low normal levels of CR1. These data
      further explain the variability observed in previous serologic studies of CR1 and
      show that DNA and protein-based genetic studies will be needed to clarify the
      role of the KN antigens in malaria.

PMID- 11313285
TI  - Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells
      in graft-versus-host disease and graft-versus-leukemia effect.
AB  - In allogeneic bone marrow transplantation (BMT) donor T cells are primarily
      responsible for antihost activity, resulting in graft-versus-host disease (GVHD),
      and for antileukemia activity, resulting in the graft-versus-leukemia (GVL)
      effect. The relative contributions of the Fas ligand (FasL) and perforin
      cytotoxic pathways in GVHD and GVL activity were studied by using FasL-defective
      or perforin-deficient donor T cells in murine parent --> F1 models for allogeneic
      bone marrow transplantation. It was found that FasL-defective B6.gld donor T
      cells display diminished GVHD activity but have intact GVL activity. In contrast,
      perforin-deficient B6.pfp(-/-) donor T cells have intact GVHD activity but
      display diminished GVL activity. Splenic T cells from recipients of B6.gld or
      B6.pfp(-/-) T cells had identical proliferative and cytokine responses to host
      antigens; however, splenic T cells from recipients of B6.pfp(-/-) T cells had no
      cytolytic activity against leukemia cells in a cytotoxicity assay. In experiments
      with selected CD4(+) or CD8(+) donor T cells, the FasL pathway was important for
      GVHD activity by both CD4(+) and CD8(+) T cells, whereas the perforin pathway was
      required for CD8-mediated GVL activity. These data demonstrate in a murine model
      for allogeneic bone marrow transplantation that donor T cells mediate GVHD
      activity primarily through the FasL effector pathway and GVL activity through the
      perforin pathway. This suggests that donor T cells make differential use of
      cytolytic pathways and that the specific blockade of one cytotoxic pathway may be
      used to prevent GVHD without interfering with GVL activity.

PMID- 11313286
TI  - T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the
      restoration of ADA activity resulted from the reversion of an inherited mutation.
AB  - Inherited deficiency of adenosine deaminase (ADA) results in one of the autosomal
      recessive forms of severe combined immunodeficiency. This report discusses 2
      patients with ADA deficiency from different families, in whom a possible reverse
      mutation had occurred. The novel mutations were identified in the ADA gene from
      the patients, and both their parents were revealed to be carriers. Unexpectedly,
      established patient T-cell lines, not B-cell lines, showed half-normal levels of
      ADA enzyme activity. Reevaluation of the mutations in these T-cell lines
      indicated that one of the inherited ADA gene mutations was reverted in both
      patients. At least one of the patients seemed to possess the revertant cells in
      vivo; however, the mutant cells might have overcome the revertant after receiving
      ADA enzyme replacement therapy. These findings may have significant implications
      regarding the prospects for stem cell gene therapy for ADA deficiency.

PMID- 11313287
TI  - Serum free light-chain measurements for identifying and monitoring patients with
      nonsecretory multiple myeloma.
AB  - Using sensitive, automated immunoassays, increased concentrations of either kappa
      or lambda free light chains (and abnormal kappa/lambda ratios) were detected in
      the sera of 19 of 28 patients with nonsecretory multiple myeloma. Four other
      patients had suppression of one or both light chains, and the remaining 5 sera
      had normal or raised free light-chain concentrations with substantially normal
      kappa/lambda ratios. Six of the patients with an elevated single free light
      chain, who were studied during follow-up, had changes in disease activity that
      were reflected by the changes in free light-chain concentrations. It is concluded
      that quantification of free light chains in serum should prove useful for the
      diagnosis and monitoring of many patients with nonsecretory myeloma.

PMID- 11313288
TI  - Identification of human telomerase reverse transcriptase-derived peptides that
      induce HLA-A24-restricted antileukemia cytotoxic T lymphocytes.
AB  - Human telomerase reverse transcriptase (hTERT) is considered a potential target
      for cancer immunotherapy because it is preferentially expressed in malignant
      cells. hTERT-derived peptides carrying motifs for HLA-A24 (HLA-A*2402), the most
      common allele among Japanese and also frequently present in persons of European
      descent, were examined for their capacity to elicit antileukemia cytotoxic T
      lymphocytes (CTLs). Two of the 5 peptides tested, VYAETKHFL and VYGFVRACL,
      appeared capable of generating hTERT peptide-specific and HLA-A24-restricted
      CTLs. The CD8(+) CTL clones specific for these hTERT peptides exerted
      cytotoxicity against leukemia cells in an HLA-A24-restricted manner. This
      cytotoxicity was inhibited by the addition of hTERT peptide-loaded autologous
      cells, suggesting that hTERT is naturally processed in leukemia cells and that
      hTERT-derived peptides are expressed on these cells and are recognized by CTLs in
      the context of HLA-A24. Taken together with the currently identified HLA-A2
      restricted CTL epitopes derived from hTERT, identification of new CTL epitopes
      presented by HLA-A24 increases the feasibility of immunotherapy for leukemia
      using hTERT-derived peptides.

PMID- 11313289
TI  - PU.1 exhibits partial functional redundancy with Spi-B, but not with Ets-1 or Elf
      1.
AB  - Previously it was shown that the Ets proteins, PU.1 and Spi-B, exhibit functional
      redundancy in B lymphocytes. To investigate the possibility that PU.1 or Spi-B or
      both share overlapping roles with Ets-1 or Elf-1, PU.1(+/-)Ets-1(-/-), PU.1(+/
      )Elf-1(-/-), and Spi-B(-/-)Ets-1(-/-) animals were generated. No blood cell
      defects were observed in these animals except those previously reported for Ets
      1(-/-) mice. Therefore, no genetic overlap was detected between PU.1 or Spi-B
      with Ets-1 or Elf-1. In contrast, the results confirmed functional redundancy for
      PU.1 and Spi-B in that PU.1(+/-)Spi-B(-/-) bone marrow progenitors yielded
      smaller colonies in methylcellulose cultures than did wild-type, PU.1(+/-) or Spi
      B(-/-) progenitors. In addition, PU.1(+/-)Spi-B(+/+), PU.1(+/-)Spi-B(+/-), and
      PU.1(+/-) Spi-B(-/-) mice displayed extramedullary splenic hematopoiesis. In
      summary, PU.1 and Spi-B regulate common target genes required for proliferation
      of hematopoietic progenitors or their committed descendants, whereas Ets-1 or Elf
      1 do not appear to regulate shared target genes with PU.1 or Spi-B.

PMID- 11313291
TI  - Visual response properties of cells in the ventral and dorsal parts of the
      macaque inferotemporal cortex.
AB  - We recorded from cells in the anterio-ventral (TEav) and anterio- dorsal (TEad)
      parts of area TE of the inferotemporal cortex and examined their responses to a
      set of 100 visual stimuli in awake, fixating monkeys. In both TEav and TEad we
      found that, depending on the stimulus, the time course of responses varied
      considerably within individual cells and that there were three main factors in
      the variation. One factor is variance in the balance between the initial
      transient part of responses around 130 ms after stimulus onset and the later part
      after 240 ms from stimulus onset. The later parts of responses were more stimulus
      selective. The second factor is variance in the latency of response onset and
      peak and the third is variance in the speed of decay from the peak within the
      initial part of the responses. Stronger responses had shorter onset and peak
      latencies and longer decay times. The results suggest that stimulus images can be
      discriminated very rapidly in TEav and TEad by detecting differences in response
      onset. TEav cells differed from TEad cells in that they were more difficult to
      activate than TEad cells: the proportion of responsive TEav cells was smaller,
      the maximal responses of individual cells were smaller than in TEad and the
      number of stimuli that evoked significant responses in individual responsive
      cells was also smaller than in TEad. Moreover, TEav cells, overall, responded
      more strongly to more colorful object images than less colorful ones, while TEad
      cells did not show such a tendency. However, the minimum onset latency of
      individual cells and the sharpness of stimulus selectivity did not differ
      significantly between TEav and TEad. Responses of TEav cells are as selective as
      those of TEad cells, although there remains a possibility that the domain of
      selectivity differs between the two areas. These results support an earlier
      anatomical finding that TEav and TEad are located at the same hierarchical level
      of separate serial pathways rather than at successive stages of a single pathway.

PMID- 11313292
TI  - Spontaneous synaptic activity of subplate neurons in neonatal rat somatosensory
      cortex.
AB  - Subplate neurons play an important role in early cortical development. To
      investigate whether these transient neurons receive synaptic inputs, we performed
      whole-cell recordings from visually identified and biocytin-labeled subplate
      cells in somatosensory cortical slices from postnatal day 0-3 rats. Subplate
      neurons had an average resting membrane potential of -55 mV and input resistance
      of approximately 1.1 G ohms. Suprathreshold current injection elicited in 67% of
      the cells repetitive action potentials at 4-13 Hz and the remaining 33% showed
      only one spike. Three classes of spontaneous postsynaptic currents (sPSCs) could
      be identified: (i) Fast sPSCs, with an average amplitude of 14 pA and a decay
      time of 6.3 ms, which showed a 95% decrease in their frequency during (+/-)-gamma
      amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor
      blockade. Cyclothiazide caused a 3.5-fold increase in the decay time, indicating
      that fast sPSCs were mediated by AMPA receptors. (ii) Slow sPSCs, with 18 pA
      amplitude and 51.2 ms decay time were blocked by the N-methyl-D-aspartate (NMDA)
      receptor antagonist CPP. (iii) Chloride-driven sPSCs, with 34.4 pA amplitude and
      123 ms decay time that were blocked by the gamma-amino-butyric acid A (GABA(A))
      receptor antagonist gabazine. While tetrodotoxin citrate (TTX) blocked completely
      NMDA-mediated slow sPSCs, the frequency of AMPA- and GABA(A)-mediated sPSCs was
      reduced in TTX by 55 and 90%, respectively. These results indicate that subplate
      neurons receive functional synaptic inputs mediated by AMPA, NMDA and GABA(A)
      receptors.

PMID- 11313293
TI  - Multiple supratemporal sources of magnetic and electric auditory evoked middle
      latency components in humans.
AB  - The supratemporal sources of the earliest auditory cortical responses (20-80 ms)
      were identified using simultaneously recorded electroencephalographic (EEG) and
      magnetoencephalographic (MEG) data. Both hemispheres of six subjects were
      recorded two or three times in different sessions in response to 8000 right-ear 1
      kHz pure tones stimuli. Four components were identified: Pa (28 ms), Nb (40 ms),
      and two subcomponents of the Pb complex, termed Pb1 (52 ms) and Pb2 (74 ms).
      Based on MEG data, the corresponding sources were localized on the anatomy using
      individual realistic head models: Pa in the medial portion of Heschl's gyri
      (H1/H2); Nb/Pb1 in the lateral aspect of the supratemporal gyrus (STG); and Pb2
      in the antero-lateral portion of Heschl's gyri. All sources were oriented antero
      superiorly. This pattern was clearest in the contralateral hemisphere, where
      these three activities could be statistically dissociated. Results agree with
      previous invasive human intracerebral recordings, with animal studies reporting
      secondary areas involved in the generation of middle latency auditory-evoked
      components, and with positron emission tomography and functional magnetic
      resonance imaging studies often reporting these three active areas although
      without temporal information. The early STG activity may be attributed to
      parallel thalamo-cortical connections, or to cortico-cortical connections between
      the primary auditory cortex and the STG, as recently described in humans.

PMID- 11313294
TI  - GHB depresses fast excitatory and inhibitory synaptic transmission via GABA(B)
      receptors in mouse neocortical neurons.
AB  - Gamma-hydroxybutyrate (GHB) is a drug of abuse which induces sedation and
      euphoria. However, overdoses can severely depress the level of consciousness or
      can be fatal especially when combined with other substances. Studies have
      suggested that the GHB-effects are mediated via actions on thalamocortical
      pathways and local neocortical circuits, although the effect of GHB at the level
      of single neocortical neurons is not clear. Using whole-cell patch-clamp
      recordings, we studied the effects of GHB on neocortical neurons in brain slices
      from 12- to 33-day-old mice. We found that GHB depressed the frequency and
      amplitude of GABAergic and glutamatergic spontaneous inhibitory and excitatory
      post-synaptic currents (IPSCs and EPSCs) driven by presynaptic action potential
      firing, while the amplitude and frequency of Ca(2+) entry-independent miniature
      IPSCs were not affected. Using minimal stimulation, GHB reduced the probability
      of release at inhibitory synapses onto neocortical layer 2/3 pyramidal cells.
      Also, GHB directly hyperpolarized layer 2/3 non-pyramidal cells by up to 11 mV
      and inhibited action potential firing. All these effects of GHB were mediated via
      GABA(B)-receptors. In conclusion, GHB activates both pre- and postsynaptic
      GABA(B)-receptors in neocortical neurons participating in fast synaptic
      transmission, leading to a powerful depression of neocortical network activity.
      We propose that GABA(B)-receptor antagonists may be useful in the treatment of
      acute GHB intoxication.

PMID- 11313295
TI  - Identification of a sensitive period of prenatal cocaine exposure that alters the
      development of the anterior cingulate cortex.
AB  - Administration of cocaine to pregnant rabbits produces robust and long-lasting
      anatomical, neurochemical and behavioral alterations in their offspring. For
      example, exposure to cocaine following implantation [embryonic day (E) 8] through
      gestation (E29) produces increased length and decreased bundling of layer III and
      V pyramidal neuron dendrites, increased parvalbumin expression in the dendrites
      of interneurons, and increased GABA levels in the anterior cingulate cortex (ACC)
      and other dopamine-rich cortical areas. We have investigated the presence of a
      sensitive period of in utero exposure during specific developmental epochs prior
      to and during the onset of cortical development that might be capable of
      producing such effects. Cocaine (3 mg/kg i.v., twice daily) or saline was
      administered during embryonic days E16-E25 (onset and peak of corticogenesis), E8
      E15 (prior to cortical plate formation), E8-E25 or E8-E29 as in earlier studies.
      Examination of the ACC in offspring exposed from E8 to E25 and from E16 to E25
      were found to induce alterations in the development of pyramidal neurons and
      interneurons that are nearly identical to those induced by the complete exposure
      (E8-E29) paradigm. No alterations were observed following the E8-E15 cocaine
      exposure. These data suggest that exposure to cocaine during E16-E25, the time of
      peak corticogenesis, appearance of cortical monoamines and onset of D(1) dopamine
      receptor expression, is necessary and sufficient to produce long-term effects on
      the organization of excitatory pyramidal neurons and inhibitory interneurons in
      the ACC.

PMID- 11313296
TI  - Fast spiking and regular spiking neural correlates of fear conditioning in the
      medial prefrontal cortex of the rat.
AB  - In order to investigate whether and how medial prefrontal cortex (mPFC) of the
      rat is involved in processing of information related to fear conditioning, we
      recorded from single units in the prelimbic and infralimbic cortex of fear
      conditioned rats in response to an explicit conditional stimulus (CS; an auditory
      tone) or contextual cues (conditioning box). The majority of units changed their
      activities significantly in response to the CS in a delay or trace conditioning
      paradigm. Both transient and tonic activity changes, including delay cell
      activity, were observed as in other behavioral tasks. When exposed to the context
      without CS delivery, most units changed their activities as well. These results
      show that both tone and contextual information are processed in the rat mPFC in
      expectation of the delivery of an aversive stimulus (electric foot shock).
      Interestingly, fast spiking cells (putative inhibitory interneurons) and regular
      spiking cells (putative projection neurons) showed different patterns of
      responses. Fast spiking cells tended to show transient responses and increased
      their firing rates following CS presentation, whereas a complementary pattern was
      observed in the regular spiking cells. Our results enhance our understanding of
      the neural mechanisms underlying prediction of an aversive stimulus in the mPFC.

PMID- 11313297
TI  - D(1) dopamine receptors potentiate nmda-mediated excitability increase in layer V
      prefrontal cortical pyramidal neurons.
AB  - The interactions between N-methyl-D-aspartate (NMDA) and D(1) dopamine receptors
      in the rat prefrontal cortex were examined using whole-cell recordings from
      pyramidal neurons. The effects of NMDA, the D(1) agonist SKF38393, or both
      compounds combined were tested on measures of cell excitability. Both NMDA (10
      100 microM) and SKF38393 (5-10 microM) independently increased the number of
      spikes and decreased the latency of the first spike evoked by intracellular
      depolarizing current pulses. Combining low doses of NMDA (5 microM) and SKF38393
      (2 microM) resulted in a marked increase of cell excitability. This synergism was
      blocked by SCH23390, protein kinase A (PKA) inhibitors, and the Ca(2+) chelator
      BAPTA, and reduced by nifedipine. These results indicate the presence of a
      dopamine- glutamate interaction in the prefrontal cortex at the postsynaptic
      level, by which D(1) dopamine receptors may maintain NMDA- mediated responses in
      prefrontal cortical pyramidal neurons through both a PKA-dependent pathway and
      Ca(2+)-dependent mechanisms.

PMID- 11313298
TI  - Somatotopic organization of human secondary somatosensory cortex.
AB  - This fMRI study investigated the human somatosensory system, especially the
      secondary somatosensory cortex (SII), with respect to its potential somatotopic
      organization. Eight subjects received electrical stimulation on their right
      second finger, fifth finger and hallux. Within SII, the typical finding for both
      fingers was a representation site within the contralateral parietal operculum
      roughly halfway between the lip of the lateral sulcus and its fundus, whereas the
      representation site of the hallux was found more medially to this position at the
      fundus of the lateral sulcus, near the posterior pole of the insula. Somatotopy
      in SII seems to be less fine-grained than in primary somatosensory cortex (SI),
      as, in contrast to SI, no separate representations of the two fingers in SII were
      observed. A similar somatotopic representation pattern between fingers and the
      hallux was also observed within ipsilateral SII, indicating somatotopy of contra-
      as well as ipsilateral SII using unilateral stimulation. Further areas exhibiting
      activation were found in the superior and inferior parietal lobule, in the
      supplementary and cingulate motor area, and in the insula.

PMID- 11313299
TI  - Early-generated preplate neurons in the developing telencephalon: inward
      migration into the developing striatum.
AB  - Specialized subsets of early-generated neurons provide the cellular cues that are
      necessary for the establishment of characteristic cell and fiber interactions in
      each brain region. During the development of the mammalian cerebral cortex, the
      early-generated cells line up in the most superficial part of the telencephalic
      pallium forming the preplate. It has been generally thought that the preplate
      derivatives are exclusively located in the cortical region and govern the early
      histogenetic phase of cortical development. However, we here disclose an
      unexpected evidence that a subset of early-generated neurons of the piriform
      preplate migrate inward into and disperse within the subcortical structure
      striatum during the embryonic stage. Their migratory route is unique and its
      direction is opposite to the ordinary migration of neuronal precursors directed
      outward from the periventricular germinal zone. After immigrating into the
      developing striatum, these early-generated cells are closely associated with the
      intrastriatal fascicules of axons. The majority of these cells are eliminated by
      apoptotic cell death during the early postnatal stage. Based on these findings,
      we propose a new concept: the preplate neurons may not only direct cortical
      histogenesis but also change their location to play a role in the development of
      subcortical structures.

PMID- 11313300
TI  - Entangled in a Web(site)?

PMID- 11313301
TI  - Intravenous cyclosporine versus intravenous corticosteroids as single therapy for
      severe attacks of ulcerative colitis.
AB  - BACKGROUND & AIMS: Cyclosporine has been effective in patients with steroid
      refractory attacks of ulcerative colitis (UC). We investigated the effects of
      intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids)
      for severe UC and compared these with the response to glucocorticosteroids.
      METHODS: Patients with a severe attack of UC were randomized to treatment with IV
      cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in
      a randomized, double-blind, controlled trial. After 8 days, patients who had a
      response received the same medication orally in combination with azathioprine.
      Patients were followed up clinically, endoscopically, and by scintigraphy. Renal
      function was assessed using urinary inulin clearances. Endpoints were clinical
      improvement, discharge from the hospital, and remission up to 12 months after
      intravenous therapy. RESULTS: Thirty patients were included. After 8 days, 8 of
      15 patients (53%) who received methylprednisolone had a response to therapy vs. 9
      of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone
      patients and 1 of 3 cyclosporine patients improved when both treatments were
      combined. No serious drug-related toxicity was observed with either treatment. At
      12 months, 7 of 9 patients (78%) initially controlled with cyclosporine
      maintained their remission vs. 3 of 8 (37%) initially treated with
      methylprednisolone. No clinically significant decrease of renal function was
      observed. CONCLUSIONS: Cyclosporine monotherapy is an effective and safe
      alternative to glucocorticosteroids in patients with severe attacks of UC.

PMID- 11313302
TI  - An engineered human antibody to TNF (CDP571) for active Crohn's disease: a
      randomized double-blind placebo-controlled trial.
AB  - BACKGROUND & AIMS: We evaluated CDP571, a humanized antibody to tumor necrosis
      factor, for the treatment of active Crohn's disease. METHODS: One hundred sixty
      nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week
      placebo-controlled trial. Patients were initially randomized to a single dose of
      10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then
      retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess
      subsequent dosing intervals. The primary endpoint was clinical response at week
      2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70
      points. RESULTS: At week 2, clinical response occurred in 45% of CDP571-treated
      patients compared with 27% of patients in the placebo group (P = 0.023). Patients
      appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of
      the results for secondary endpoints were statistically significant. The frequency
      of severe or serious adverse events was similar among all groups. CONCLUSIONS:
      CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment
      of patients with moderate-to-severe Crohn's disease. Preliminary evidence
      suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks
      may also be beneficial, but additional studies are needed.

PMID- 11313303
TI  - Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active
      Crohn's disease.
AB  - BACKGROUND & AIMS: ISIS-2302, an antisense oligonucleotide directed against
      intercellular adhesion molecule 1, was effective in steroid refractory Crohn's
      disease in a pilot trial. The aim of this study was to investigate safety and
      efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). METHODS: A dose
      interval, multicenter, placebo-controlled trial was conducted in 75 patients with
      steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The
      primary endpoint was steroid-free remission (CDAI <150) at week 14. RESULTS: Only
      2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary
      endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8
      of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater
      proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10
      mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and
      a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%,
      respectively]). Treatment with ISIS-2302 was safe. The most common side effects
      were injection site reactions in the active treatment group (23% in ISIS-2302
      treated patients vs. none in placebo patients). No statistically significant
      differences in the frequency of side effects were detected between dose groups.
      CONCLUSIONS: The trial did not prove clinical efficacy of ISIS-2302 based on the
      primary endpoint. Positive trends were observed in some of the secondary
      endpoints.

PMID- 11313304
TI  - ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF
      antibody treatment in Crohn's disease.
AB  - BACKGROUND & AIMS: In the clinical trial, a lower response to infliximab was
      observed in some patients after multiple infusions, suggesting that clinical
      subgroups of Crohn's disease (CD) exist based on response to anti-tumor necrosis
      factor (anti-TNF). The aim of this study was to characterize these subgroups
      further by antineutrophil cytoplasmic antibody (ANCA) pattern and TNF genotype.
      METHODS: Crohn's Disease Activity Index (CDAI) data from the North American
      patients in the clinical trial (n = 59) were evaluated as the response parameter.
      Speckled ANCA (sANCA) subjects were ANCA positive by ELISA with a speckling over
      the entire neutrophil on indirect immunofluorescence. Genotypes were determined
      for polymorphisms in the TNF/lymphotoxin alpha (LTA) region. RESULTS: Response to
      infliximab as median change in CDAI was placebo (least response) < perinuclear
      ANCA (pANCA) < not pANCA or sANCA < sANCA (greatest response) (P(overall) =
      0.003; 4 weeks). The response of subjects with sANCA was significantly different
      from that of placebo at all time points; that of pANCA subjects was not.
      Homozygotes for the LTA NcoI-TNFc-aa13L-aa26 haplotype 1-1-1-1 did not respond
      (P(overall) = 0.007). CONCLUSIONS: These observations suggest that sANCA may
      identify a CD subgroup with a better response to infliximab and that pANCA and
      homozygosity for the LTA 1-1-1-1 haplotype may identify subgroups with a poorer
      response.

PMID- 11313305
TI  - Family history as a risk factor for colorectal cancer in inflammatory bowel
      disease.
AB  - BACKGROUND & AIMS: Familial colorectal cancer (CRC) is a risk factor for CRC in
      healthy individuals and, as indicated by case-control studies, possibly in
      ulcerative colitis. Little is known about the cancer risk in familial
      inflammatory bowel disease (IBD). We assessed the significance of familial CRC,
      or IBD, on the risk for CRC in patients with IBD. METHODS: Population-based
      cohort study of 19,876 individuals with ulcerative colitis or Crohn's disease
      born between 1941 and 1995. Registry-based follow-up and assessment of familial
      CRC, and IBD. Risk of CRC assessed as incidence proportion ("absolute risk," IP)
      and relative risk (RR). RESULTS: Familial CRC was associated with a more than 2
      fold risk of CRC (adjusted RR = 2.5, 95% confidence interval 1.4-4.4) and an
      increase in the IP of CRC at 54 years of age from 3.8% to 6.9%. Patients with a
      first-degree relative diagnosed with CRC before 50 years of age had a higher RR
      (9.2, 95% confidence interval 3.7-23) and the highest IP (29%). No association
      with familial IBD was observed. CONCLUSIONS: Information on family history of CRC
      may be a simple way to identify individuals with IBD at elevated risk of
      developing CRC.

PMID- 11313306
TI  - The cardiac K+ channel KCNQ1 is essential for gastric acid secretion.
AB  - BACKGROUND & AIMS: Gastric H+ secretion via the H+/K+-adenosine triphosphatase is
      coupled to the uptake of K+. However, the molecular identity of luminal K+
      channels enabling K+ recycling in parietal cells is unknown. This study was aimed
      to investigate these luminal K+ channels. METHODS: Acid secretion was measured in
      vivo and in vitro; KCNQ1 protein localization was assessed by immunofluorescence,
      and acid-sensitivity of KCNQ1 by patch-clamp. RESULTS: We identified KCNQ1, which
      is mutated in cardiac long QT syndrome, as a K+ channel located in tubulovesicles
      and apical membrane of parietal cells, where it colocalized with H+/K+-adenosine
      triphosphatase. Blockade of KCNQ1 current by 293B led to complete inhibition of
      acid secretion. The putative KCNQ1 subunits, KCNE2 and KCNE3, were abundant in
      human stomach; KCNE1, however, was absent. Coexpression of KCNE3/KCNQ1 in COS
      cells led to an acid-insensitive current; KCNE2/KCNQ1 was activated by low
      extracellular pH. CONCLUSIONS: We identified KCNQ1 as the missing luminal K+
      channel in parietal cells and characterized its crucial role in acid secretion.
      Because KCNE3 and KCNE2 are expressed in human stomach, one or both are
      candidates to coassemble with KCNQ1 in parietal cells. Thus, stomach- and subunit
      specific inhibitors of KCNQ1 might offer new therapeutical perspectives for
      peptic ulcer disease.

PMID- 11313307
TI  - Keratinocyte growth factor promotes goblet cell differentiation through
      regulation of goblet cell silencer inhibitor.
AB  - BACKGROUND & AIMS: Keratinocyte growth factor (KGF) is an epithelial cell
      specific growth factor. Previous reports demonstrated that KGF induces
      differentiation of epithelial cells of gastrointestinal tract in vivo, especially
      goblet cell-specific lineage stimulation. Intestinal trefoil factor (ITF) is
      selectively expressed in intestinal goblet cells and its expression correlates
      with intestinal goblet cell differentiation. In this study, we analyzed the
      mechanism of KGF modulation of goblet cell differentiation through
      characterization of its effects on ITF gene expression. METHODS: Subclone H2 of
      the human colonic epithelial cell line HT-29, which can be induced to intestinal
      goblet cells, was treated with KGF and characterized by Northern and Western blot
      analyses, transient transfection assays, and electrophoretic mobility shift
      assays (EMSAs). RESULTS: KGF promoted differentiation of H2 cells to goblet cells
      as reflected by induced ITF expression. Transient transfection assays revealed
      that KGF regulates mouse ITF transcription through the goblet cell silencer
      inhibitor (GCSI) element, which is essential for goblet cell-specific expression
      of ITF. EMSAs showed that KGF induces GCSI binding protein (GCSI-BP).
      CONCLUSIONS: KGF promotes goblet cell differentiation through the induction of
      GCSI-BP, a goblet cell-specific transcription factor. GCSI-BP may play a central
      role in intestinal goblet cell differentiation.

PMID- 11313308
TI  - Inhibition of the phosphatidylinositol 3-kinase pathway contributes to HT29 and
      Caco-2 intestinal cell differentiation.
AB  - BACKGROUND & AIMS: Phosphatidylinositol 3-kinase (PI3K), an important mediator of
      intracellular signal transduction, has been shown to affect proliferation,
      differentiation, and apoptosis in a number of cells; the role of PI3K in
      intestinal cell differentiation is not known. METHODS: The effect of PI3K
      inhibition on enterocyte-like differentiation of the human colon cancer cells,
      HT29 and Caco-2, was assessed using complementary approaches (i.e., chemical
      inhibition with wortmannin, transfection with a dominant negative p85 mutant, or
      overexpression of the tumor suppressor gene phosphatase and tensin homologue
      deleted on chromosome 10 [PTEN]). Brush-border enzyme (intestinal alkaline
      phosphatase [IAP] and sucrase) activities, IAP messenger RNA levels, and IAP
      promoter induction were measured. RESULTS: The PI3K inhibitor, wortmannin, in
      combination with sodium butyrate, synergistically induced IAP and sucrase enzyme
      activities and IAP messenger RNA levels in a time- and dose-dependent fashion.
      Consistent with these results, cotransfection using the dominant negative mutant
      of p85 (Deltap85) induced IAP promoter activity. Moreover, overexpression of
      PTEN, which antagonizes PI3K, significantly augmented the induction of IAP enzyme
      activity in HT29 and Caco-2 cells treated with sodium butyrate and in
      spontaneously differentiated Caco-2 cells. CONCLUSIONS: Our results show that
      inhibition of PI3K significantly enhances enterocyte-like differentiation of HT29
      and Caco-2 cells. Taken together, our findings suggest a contributory role for
      the PI3K/PTEN pathway in intestinal cell differentiation.

PMID- 11313309
TI  - Inhibition of Na+,K+-ATPase by interferon gamma down-regulates intestinal
      epithelial transport and barrier function.
AB  - BACKGROUND & AIMS: To determine how interferon (IFN)-gamma inhibits epithelial
      barrier and ion transport functions, intestinal T84 cells were studied. METHODS:
      Acute and chronic effects of IFN-gamma on T84 barrier function, Na+,K+-adenosine
      triphosphatase (ATPase) activity, and certain ion transport and tight junctional
      proteins were determined. To assess the role of Na+,K+-ATPase and intracellular
      Na+, similar studies with the Na+,K+-ATPase inhibitor ouabain and Na+ ionophore
      monensin were performed. To determine the role of nitric oxide (NO), the NO donor
      SPER-NO was used. RESULTS: IFN-gamma acutely (<6 hour) decreased cellular Na+,K+
      ATPase activity, followed later (>24 hours) by decreases in expression of
      Na/K/2Cl, the alpha subunit of Na+,K+-ATPase, occludin, and ZO-1. In contrast,
      cystic fibrosis transmembrane conductance regulator or the Na+ pump beta subunit
      were unchanged. Ouabain and monensin caused nearly identical changes to IFN
      gamma. Incubation in low Na+ media significantly blunted the chronic effects of
      IFN-gamma. Hypotonic-induced cell swelling, in contrast, had effects similar to
      IFN-gamma but did not alter the expression of the Na+ pump alpha subunit. The NO
      donor SPER-NO rapidly inhibited Na+,K+-ATPase and also down-regulated transport
      and barrier proteins. CONCLUSIONS: IFN-gamma inhibition of Na+,K+-ATPase activity
      acutely causes increases in intracellular Na(i) concentration and cell volume,
      which are distinct signaling events that ultimately result in a leaky and
      dysfunctional epithelium associated with chronic inflammation.

PMID- 11313310
TI  - Duodenal expression of a putative stimulator of Fe transport and transferrin
      receptor in anemia and hemochromatosis.
AB  - BACKGROUND & AIMS: Stimulator of Fe Transport (SFT) and transferrin receptor
      (TfR) are proteins involved in iron transport. This study evaluated iron
      metabolism protein expression in duodenal biopsy specimens from controls and
      patients with abnormal iron metabolism. METHODS: Twelve controls, 8 patients with
      iron deficiency anemia, 7 with HFE-related hemochromatosis, and 6 with non-HFE
      related iron overload were studied. Immunohistochemistry was performed on
      duodenal biopsy specimens with anti-TfR and anti-SFT antibodies which recognize a
      putative stimulator of Fe transport of ~80 kilodaltons. RESULTS: In controls, the
      putative stimulator of Fe transport was expressed in the middle and distal part
      of the villi in the subapical cytoplasmatic region. Its expression increased in
      anemics and, to a lesser degree, in HFE-related hemochromatotics, whereas it was
      reduced in patients with non-HFE-related iron overload. TfR expression showed a
      crypt-to-tip gradient in controls, but not in anemics, in whom it was uniformly
      overexpressed. TfR expression was intermediate in HFE-related hemochromatotics
      and similar to controls in non-HFE-related iron overload. CONCLUSIONS: Expression
      of the putative stimulator of Fe transport and TfR increases in iron deficiency.
      Increased expression of both proteins is present only in HFE-related
      hemochromatotics suggesting that other factors may be involved in determining non
      HFE-related iron overload phenotype.

PMID- 11313311
TI  - Expression of the duodenal iron transporters divalent-metal transporter 1 and
      ferroportin 1 in iron deficiency and iron overload.
AB  - BACKGROUND & AIMS: Imbalances of iron homeostasis are accompanied by alterations
      of intestinal iron absorption. The identification of divalent-metal transporter 1
      (DMT1) and ferroportin 1 (FP1) has improved our understanding of transmembrane
      iron trafficking. To gain insight into the regulatory properties of these
      transporters in the duodenum, we studied their expression in patients with
      hereditary hemochromatosis (HFE-associated and non-HFE-associated), secondary
      iron overload, and iron deficiency. METHODS: DMT1, FP1 messenger RNA (mRNA), and
      protein expression were analyzed in duodenal biopsy specimens from patients by
      means of TaqMan real-time polymerase chain reaction, Western blotting technique,
      and immunohistochemistry. RESULTS: DMT1 and FP1 mRNA levels are positively
      correlated with each other in all patient groups (P < 0.001). Moreover, DMT1 and
      FP1 mRNA levels were significantly increased in patients with iron deficiency,
      HFE and non-HFE hemochromatosis, whereas they were unchanged in patients with
      secondary iron overload. Alterations in DMT1 and FP1 mRNA levels were paralleled
      by comparable changes in the duodenal expression of these proteins. In patients
      with normal iron status or iron deficiency, significant negative correlations
      between DMT1, FP1 mRNA, and serum iron parameters were found, which were absent
      in subjects with primary hemochromatosis. CONCLUSIONS: DMT1 and FP1 are centrally
      involved in iron uptake/transfer in the duodenum and in the adaptive changes of
      iron homeostasis to iron deficiency and overload.

PMID- 11313312
TI  - Intestinal iron uptake determined by divalent metal transporter is enhanced in
      HFE-deficient mice with hemochromatosis.
AB  - BACKGROUND & AIMS: Overexpression of duodenal divalent metal transporter (DMT1)
      messenger RNA occurs in hemochromatosis and HFE-knockout mice, suggesting that
      DMT1 mediates enhanced absorption of iron; however, increased expression of
      functional DMT1 protein has yet to be substantiated. We examined the role of DMT1
      and the mucosal iron uptake defect in HFE-knockout mice. METHODS: Unidirectional
      iron uptake of 59Fe by small intestinal mucosa in vitro was compared between
      matched pairs of HFE-knockout and wild-type mice. DMT1-specific antibodies were
      used to block iron transport and to quantify duodenal protein expression.
      RESULTS: Ferrous iron uptake at 3.5-450 micromol/L was greatly enhanced in HFE
      knockouts compared with wild-type, the apparent V(max) for Fe2+ transport being
      doubled (P < 0.01). Supplied as Fe3+, uptake was only enhanced in HFE-knockouts
      at < or =18 micromol/L, when the iron was almost completely converted to Fe2+ by
      mucosal ferrireductases. DMT1 antibody reduced the apparent Vmax for mucosal Fe2+
      transport in HFE-knockouts to below wild-type control values (P < 0.02);
      immunoreactive mucosal DMT1 protein was increased nearly 2-fold in HFE-knockouts
      (P < 0.01). CONCLUSIONS: Disruption of the HFE gene up-regulates functional DMT1
      transporters and enhances uptake of ferrous iron by this mechanism; DMT1 also
      mediates increased uptake after reduction of ferric iron presented at
      physiological concentrations.

PMID- 11313313
TI  - Increased calcium influx is responsible for the sustained mechanical tone in
      colon from dystrophic (mdx) mice.
AB  - BACKGROUND & AIMS: Proximal colon from dystrophic mice develops spontaneous tone
      increment, but the mechanisms involved in its development have not been
      investigated. This study examined whether alterations in the properties of cell
      membrane calcium channels and/or sarcoplasmic reticular (SR) Ca2+-adenosine
      triphosphatase (ATPase) contribute to tone development. METHODS: Effects of
      calcium-free solution, nifedipine, pinaverium (calcium channel blockers), and
      cyclopiazonic acid (CPA; SR Ca2+-ATPase inhibitor) on the contractile activity of
      colon from mdx and control mice were determined. RESULTS: Calcium-free solution
      abolished spontaneous contractions in both preparations, but decreased the tone
      only in mdx mice. Nifedipine or pinaverium abolished phasic contractions, acting
      with different sensitivities on the 2 preparations. They also decreased the tone
      in colons of mdx mice, and Ca2+-free solution did not cause any further loss of
      tone. CPA, after an early contractile effect, abolished spontaneous contractions
      in control animals. It did not suppress the contractile activity in mdx mice. CPA
      inhibited the repletion of intracellular calcium stores in both tissues to the
      same degree. CONCLUSIONS: Increased Ca2+ influx through L-type voltage-dependent
      Ca2+ channels seems to be responsible for the sustained mechanical tone of
      proximal colon from mdx mice. The mechanisms for sequestering calcium appear to
      be unaltered.

PMID- 11313314
TI  - Viral kinetics in patients with chronic hepatitis C treated with standard or
      peginterferon alpha2a.
AB  - BACKGROUND & AIMS: Covalent attachment of a 40-kilodalton polyethylene glycol
      moiety to interferon alpha2a (peginterferon alpha2a) results in sustained
      delivery and reduced clearance compared with standard interferon alpha2a. The aim
      of the study was to compare viral kinetics in patients treated with standard or
      peginterferon alpha2a. METHODS: Patients with chronic hepatitis C were randomly
      assigned to receive either standard interferon alpha2a thrice weekly (n = 16) or
      180 microg peginterferon alpha2a once weekly (n = 17) for 48 weeks. HCV RNA was
      quantitated before and frequently during treatment. RESULTS: The extent of the
      second-phase decline of HCV RNA, representing the degradation rate of infected
      cells during therapy for responding patients, was 0.02 +/- 0.03 day(-1) (HCV-1),
      0.88 +/- 0.64 day(-1) (HCV non-1), 0.06 +/- 0.08 day(-1) (HCV-1), and 0.44 +/-
      0.33 day(-1) (HCV non-1) in patients treated with standard or peginterferon
      alpha2a, respectively. The second-phase decline was low (<0.05 day(-1)) in most
      patients without a virological end-of-treatment response, and the second-phase
      decline was high (>0.25 day(-1)) in all patients with sustained virological
      response. CONCLUSIONS: The degradation rate of infected cells is HCV genotype
      dependent. Treatment with peginterferon alpha2a may reinforce the death rate of
      infected cells (particularly in HCV-1-infected patients) or stabilize the
      therapeutic effect on viral production. The second-phase decline of HCV RNA is
      predictive of virological sustained response.

PMID- 11313315
TI  - The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis
      to cirrhosis of adulthood.
AB  - BACKGROUND & AIMS: We have specified the features of progressive familial
      intrahepatic cholestasis type 3 and investigated in 31 patients whether a defect
      of the multidrug resistance 3 gene (MDR3) underlies this phenotype. METHODS: MDR3
      sequencing, liver MDR3 immunohistochemistry, and biliary phospholipid dosage were
      performed. RESULTS: Liver histology showed a pattern of biliary cirrhosis with
      patency of the biliary tree. Age at presentation ranged from the neonatal period
      to early adulthood. Sequence analysis revealed 16 different mutations in 17
      patients. Mutations were identified on both alleles in 12 patients and only on 1
      allele in 5. Four mutations lead to a frame shift, 2 are nonsense, and 10 are
      missense. An additional missense mutation probably representing a polymorphism
      was found in 5 patients. MDR3 mutations were associated with abnormal MDR3
      canalicular staining and a low proportion of biliary phospholipids. Gallstones or
      episodes of cholestasis of pregnancy were found in patients or parents. Children
      with missense mutations had a less severe disease and more often a beneficial
      effect of ursodeoxycholic acid therapy. CONCLUSIONS: At least one third of the
      patients with a progressive familial intrahepatic cholestasis type 3 phenotype
      have a proven defect of MDR3. This gene defect should also be considered in adult
      liver diseases.

PMID- 11313316
TI  - MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder
      cholesterol cholelithiasis.
AB  - BACKGROUND & AIMS: Many studies indicate that gallstone susceptibility has
      genetic components. MDR3 is the phosphatidylcholine translocator across the
      hepatocyte canalicular membrane. Because phospholipids are a carrier and a
      solvent of cholesterol in hepatic bile, we hypothesized that a defect in the MDR3
      gene could be the genetic basis for peculiar forms of cholesterol gallstone
      disease, in particular those associated with symptoms and cholestasis without
      evident common bile duct stone. METHODS: We studied 6 adult patients with a
      peculiar form of cholelithiasis. MDR3 gene sequence was determined by reverse
      transcription polymerase chain reaction amplification of mononuclear cell RNAs
      followed by direct sequencing. Hepatic bile was analyzed in 2 patients. RESULTS:
      All patients shared the following features: at least 1 episode of biliary colic,
      pancreatitis, or cholangitis; biochemical evidence of chronic cholestasis;
      recurrence of symptoms after cholecystectomy; presence of echogenic material in
      the intrahepatic bile ducts; and prevention of recurrence by ursodeoxycholic acid
      therapy. Hepatic bile composition showed a high cholesterol/phospholipid ratio
      and cholesterol crystals. In all patients, we found MDR3 gene mutations involving
      a conserved amino acid region. CONCLUSIONS: These preliminary observations
      suggest that MDR3 gene mutations represent a genetic factor involved in this
      peculiar form of cholesterol gallstone disease in adults. They require further
      studies to assess the prevalence of MDR3 gene defects in symptomatic and silent
      cholesterol gallstone disease.

PMID- 11313317
TI  - Homozygosity for alanine in the mitochondrial targeting sequence of superoxide
      dismutase and risk for severe alcoholic liver disease.
AB  - BACKGROUND & AIMS: For similar ethanol consumption, some subjects only develop
      macrovacuolar steatosis whereas others develop severe liver lesions. A genetic
      dimorphism encodes for either alanine or valine in the mitochondrial targeting
      sequence of manganese superoxide dismutase and could modulate its mitochondrial
      import. METHODS: The DNA of 71 white patients with alcoholic liver disease and 79
      white blood donors was amplified and genotyped. RESULTS: The frequency of the
      alanine-encoding allele and the percentage of alanine homozygotes were higher in
      all patients than in controls and increased with the severity of liver lesions.
      The percentage of alanine homozygotes was 19% in controls, 17% in alcoholic
      patients with macrovacuolar steatosis, 43% in patients with microvesicular
      steatosis, 58% in patients with alcoholic hepatitis, and 69% in patients with
      cirrhosis. Alcohol consumption in alcoholics was similar whatever the genotype.
      Alanine homozygosity did not change the risk of developing macrovacuolar
      steatosis in alcoholics, but increased by 3-fold that of microvesicular
      steatosis, and 6- and 10-fold that of alcoholic hepatitis and cirrhosis.
      CONCLUSIONS: Homozygosity for alanine in the mitochondrial targeting sequence of
      manganese superoxide does not modify alcohol consumption and the risk of
      macrovacuolar steatosis in alcoholics but is a major risk factor for severe
      alcoholic liver disease.

PMID- 11313318
TI  - Mapping MHC-encoded susceptibility and resistance in primary sclerosing
      cholangitis: the role of MICA polymorphism.
AB  - BACKGROUND & AIMS: Recent studies suggest that major histocompatibility complex
      encoded susceptibility to primary sclerosing cholangitis (PSC) maps to the HLA B
      TNFA region on chromosome 6p21.3. METHODS: The present study uses a standard
      polymerase chain reaction protocol to investigate the 16 common alleles of the
      MICA locus as candidates in 2 patient populations (King's College Hospital,
      London, and John Radcliffe Hospital, Oxford). RESULTS: The MICA*002 allele was
      found in 4 of 62 (6.4%) patients and none of 50 patients vs. 41 of 118 (35%)
      controls (pc = 0.00018, odds ratio [OR] = 0.12, and P = 0.0000016, OR = 0.0,
      respectively). Overall, the MICA*008 allele was more common in PSC (gene
      frequency 66% vs. 48% of controls, P = 0.0023, OR = 2.11). However, unlike
      MICA*002 in which the difference was a result of the absence of MICA*002
      heterozygotes, the MICA*008 association may be caused by an increased frequency
      of MICA*008 homozygosity in patients (58% vs. 22%, pc = 0.000015, OR = 5.01 and
      58% vs. 22%, P = 0.0000056, OR = 4.51, respectively). Though MICA*008 is found on
      the ancestral 8.1 haplotype, stratification analysis indicates that this
      association is independent of B8 and other HLA haplotypes associated with PSC.
      CONCLUSIONS: The MICA*002 allele has a strong dominant effect in reducing the
      risk of PSC, whereas the increased risk of disease associated with MICA*008 may
      be a recessive effect requiring 2 copies of the MICA*008 allele.

PMID- 11313319
TI  - Treatment of refractory microscopic colitis with azathioprine and 6
      mercaptopurine.
AB  - Many patients with microscopic colitis will respond to antidiarrheal medications
      or to anti-inflammatory therapy with 5-aminosalicylates, although a few require
      corticosteroids. Some patients do not tolerate corticosteroid side effects, and a
      small subset are dependent on or refractory to corticosteroids. We report our
      experience with azathioprine and 6-mercaptopurine in patients with microscopic
      colitis.

PMID- 11313320
TI  - The lymphoid liver: considerations on pathways to autoimmune injury.
AB  - Immunologic injury in the liver involves immigrant T and B lymphocytes and a
      resident lymphoid population that comprises distinct lymphocytic cells and
      accessory cells. The forerunner to autoimmunity is breaching of natural self
      tolerance and hence the disruption of a fundamental property of the immune
      system. Such breaching occurs by processes that include inflammatory activation
      of immunocytes and macrophages, spillage of intracellular constituents, and
      epitope mimicry by constituents of microorganisms, with these acting on a
      genetically conditional phenotype; compounding factors include aberrations of
      apoptosis, whether insufficient or excess. The downstream end requires
      specifically directed inflammatory leukocyte traffic as an essential component of
      autoimmune expressions in the liver. The culmination is an orchestrated attack on
      hepatocytes or biliary epithelial cells by multiple effector pathways. Progress
      in type 1 autoimmune hepatitis still requires knowledge of a disease-specific
      autoantigen(s) involved in T-cell reactivity, although such knowledge in type 2
      autoimmune hepatitis, in which the known autoantigen is cytochrome P4502D6, has
      not yet been integrated into a clearly defined scheme of pathogenesis. For PBC
      there has been a very promising amalgamation of molecular knowledge of the
      mitochondrial autoantigens. Future insights require deeper analysis of molecular,
      genetic, macroenvironmental, and microenvironmental elements in predisposition.

PMID- 11313321
TI  - Autoimmune hepatitis: clinical challenges.

PMID- 11313322
TI  - American Gastroenterological Association. Our new president--Jon I. Isenberg,
      M.D.

PMID- 11313323
TI  - American Gastroenterological Association medical position statement: Celiac
      Sprue.

PMID- 11313324
TI  - AGA technical review on Celiac Sprue. American Gastroenterological Association.

PMID- 11313325
TI  - Intravenous cyclosporine in severe ulcerative colitis: ready to stand alone?

PMID- 11313326
TI  - The yin and yang of intestinal differentiation: key roles for lipid signaling.

PMID- 11313327
TI  - How can mathematics help us understand HCV?

PMID- 11313328
TI  - MDR3 mutations: a glimpse into pandora's box and the future of canalicular
      pathophysiology.

PMID- 11313329
TI  - Methotrexate for the maintenance of remission in Crohn's disease.

PMID- 11313330
TI  - Cesarean for C? Possibly...

PMID- 11313331
TI  - Bile acids regulate their own synthesis: the nuclear connection.

PMID- 11313333
TI  - A new pathway for heavy metal detoxification in animals. Phytochelatin synthase
      is required for cadmium tolerance in Caenorhabditis elegans.
AB  - Increasing emissions of heavy metals such as cadmium, mercury, and arsenic into
      the environment pose an acute problem for all organisms. Considerations of the
      biochemical basis of heavy metal detoxification in animals have focused
      exclusively on two classes of peptides, the thiol tripeptide, glutathione (GSH,
      gamma-Glu-Cys-Gly), and a diverse family of cysteine-rich low molecular weight
      proteins, the metallothioneins. Plants and some fungi, however, not only deploy
      GSH and metallothioneins for metal detoxification but also synthesize another
      class of heavy metal binding peptides termed phytochelatins (PCs) from GSH. Here
      we show that PC-mediated heavy metal detoxification is not restricted to plants
      and some fungi but extends to animals by demonstrating that the ce-pcs-1 gene of
      the nematode worm Caenorhabditis elegans encodes a functional PC synthase whose
      activity is critical for heavy metal tolerance in the intact organism.

PMID- 11313334
TI  - A single domain of the replication termination protein of Bacillus subtilis is
      involved in arresting both DnaB helicase and RNA polymerase.
AB  - The current models that have been proposed to explain the mechanism of
      replication termination are (i) passive arrest of a replication fork by the
      terminus (Ter) DNA-terminator protein complex that impedes the replication fork
      and the replicative helicase in a polar fashion and (ii) an active barrier model
      in which the Ter-terminator protein complex arrests a fork not only by DNA
      protein interaction but also by mechanistically significant terminator protein
      helicase interaction. Despite the existence of some evidence supporting in vitro
      interaction between the replication terminator protein (RTP) and DnaB helicase,
      there has been continuing debate in the literature questioning the validity of
      the protein-protein interaction model. The objective of the present work was two
      fold: (i) to reexamine the question of RTP-DnaB interaction by additional
      techniques and different mutant forms of RTP, and (ii) to investigate if a common
      domain of RTP is involved in the arrest of both helicase and RNA polymerase. The
      results validate and confirm the RTP-DnaB interaction in vitro and suggest a
      critical role for this interaction in replication fork arrest. The results also
      show that the Tyr(33) residue of RTP plays a critical role both in the arrest of
      helicase and RNA polymerase.

PMID- 11313336
TI  - Targeting of p300 to the interleukin-2 promoter via CREB-Rel cross-talk during
      mitogen and oncogenic molecular signaling in activated T-cells.
AB  - In this report, we explore the mechanisms of targeting of p300 to the interleukin
      2 (IL-2) promoter in response to mitogenic and oncogenic molecular signals.
      Recruitment of p300 by cAMP-responsive element-binding protein-Rel cross-talk at
      the composite CD28 response element (CD28RE)-TRE element of the IL-2 promoter is
      essential for promoter inducibility during T-cell activation, and CD28RE-TRE is
      the exclusive target of the human T-cell lymphotropic virus type I oncoprotein
      Tax. The intrinsic histone acetyltransferase activity of p300 is dispensable for
      activation of the IL-2 promoter, and the N-terminal 743 residues contain the
      minimal structural requirements for synergistic transactivation of the CD28RE
      TRE, the IL-2 promoter, and endogenous IL-2 gene expression. Mutational analysis
      of p300 reveals differential structural requirements for the N-terminal p300
      module by individual cis-elements within the IL-2 promoter. These findings
      provide evidence that p300 assembles at the IL-2 promoter to form an enhanceosome
      like signal transduction target that is centrally integrated at the CD28RE-TRE
      element of the IL-2 promoter through specific protein module-targeted
      associations in activated T-cells.

PMID- 11313335
TI  - Thioflavin T is a fluorescent probe of the acetylcholinesterase peripheral site
      that reveals conformational interactions between the peripheral and acylation
      sites.
AB  - Three-dimensional structures of acetylcholinesterase (AChE) reveal a narrow and
      deep active site gorge with two sites of ligand binding, an acylation site at the
      base of the gorge, and a peripheral site near the gorge entrance. Recent studies
      have shown that the peripheral site contributes to catalytic efficiency by
      transiently binding substrates on their way to the acylation site, but the
      question of whether the peripheral site makes other contributions to the
      catalytic process remains open. A possible role for ligand binding to the
      peripheral site that has long been considered is the initiation of a
      conformational change that is transmitted allosterically to the acylation site to
      alter catalysis. However, evidence for conformational interactions between these
      sites has been difficult to obtain. Here we report that thioflavin T, a
      fluorophore widely used to detect amyloid structure in proteins, binds
      selectively to the AChE peripheral site with an equilibrium dissociation constant
      of 1.0 microm. The fluorescence of the bound thioflavin T is increased more than
      1000-fold over that of unbound thioflavin T, the greatest enhancement of
      fluorescence for the binding of a fluorophore to AChE yet observed. Furthermore,
      when the acylation site ligands edrophonium or m-(N, N,N
      trimethylammonio)trifluoroacetophenone form ternary complexes with AChE and
      thioflavin T, the fluorescence is quenched by factors of 2.7-4.2. The observation
      of this partial quenching of thioflavin T fluorescence is a major advance in the
      study of AChE for two reasons. First, it allows thioflavin T to be used as a
      reporter for ligand reactions at the acylation site. Second, it indicates that
      ligand binding to the acylation site initiates a change in the local AChE
      conformation at the peripheral site that quenches the fluorescence of bound
      thioflavin T. The data provide strong evidence in support of a conformational
      interaction between the two AChE sites.

PMID- 11313337
TI  - Retrovirus molecular conjugates. A novel, high transduction efficiency,
      potentially safety-improved, gene transfer system.
AB  - Two significant barriers limit the use of amphotropic retrovirus for human gene
      transfer protocols: 1) low transduction efficiency in cells with low receptor
      expression and 2) safety concerns originating from the risk of formation and
      propagation of replication competent virus in vivo. In principle, if ecotropic
      retrovirus, which is incapable of infecting human cells, could be transiently
      modified to effectively transduce human cells, this safety risk could be
      alleviated. Here we demonstrate that formation of amphotropic retrovirus
      polylysine molecular conjugates (aMMLV-PL) enhanced gene transfer up to 10-fold
      in a variety of human cell lines over the equivalent of unconjugated vector
      (aMMLV). The polylysine modification and formation of ecotropic retrovirus
      molecular conjugates (eMMLV-PL) permitted effective and stable transduction of
      different human cell lines as well as primary human bone marrow stroma cells at
      frequencies of greater than 80%. It is conceivable that this novel ecotropic
      based conjugate retrovirus vector could also potentially provide enhanced safety
      characteristics not only over amphotropic retrovirus vectors but also over
      genetically tropism-modified recombinant ecotropic vectors. In contrast to
      genetic modifications, physical or chemical modifications are not propagated.
      Thus, formation of replication competent eMMLV from conjugates would be self
      limited and would not result in virus propagation in humans.

PMID- 11313338
TI  - 1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine
      peptides.
AB  - The recent crystal structure of Pin1 protein bound to a doubly phosphorylated
      peptide from the C-terminal domain of RNA polymerase II revealed that binding
      interactions between Pin1 and its substrate take place through its Trp-Trp (WW)
      domain at the level of the loop Ser(11)-Arg(12) and the aromatic pair Tyr(18)
      Trp(29), and showed a trans conformation for both pSer-Pro peptide bonds.
      However, the orientation of the ligand in the aromatic recognition groove still
      could be sequence-specific, as previously observed in SH3 domains complexed by
      peptide ligands or for different class of WW domains (Zarrinpar, A., and Lim, W.
      A. (2000) Nat. Struct. Biol. 7, 611-613). Because the bound peptide conformation
      could also differ as observed for peptide ligands bound to the 14-3-3 domain,
      ligand orientation and conformation for two other biologically relevant
      monophosphate substrates, one derived from the Cdc25 phosphatase of Xenopus
      laevis (EQPLpTPVTDL) and another from the human tau protein (KVSVVRpTPPKSPS) in
      complex with the WW domain are here studied by solution NMR methods. First, the
      proton resonance perturbations on the WW domain upon complexation with both
      peptide ligands were determined to be essentially located in the positively
      charged beta-hairpin Ser(11)-Gly(15) and around the aromatic Trp(29).
      Dissociation equilibrium constants of 117 and 230 microm for Cdc25 and tau
      peptides, respectively, were found. Several intermolecular nuclear Overhauser
      effects between WW domain and substrates were obtained from a ligand-saturated
      solution and were used to determine the structures of the complexes in solution.
      We found a similar N to C orientation as the one observed in the crystal complex
      structure of Pin1 and a trans conformation for the pThr-Pro peptidic bond in both
      peptide ligands, thereby indicating a unique binding scheme for the Pin1 WW
      domain to its multiple substrates.

PMID- 11313339
TI  - DNA binding of TEA/ATTS domain factors is regulated by protein kinase C
      phosphorylation in human choriocarcinoma cells.
AB  - Transcription enhancer factor 1 (TEF-1) controls the expression of a diverse set
      of genes. Previous studies implicated protein kinase C (PKC)-mediated signal
      transduction in modulating TEF function. We demonstrate that in human
      choriocarcinoma BeWo cells, the PKC activator 12-O-tetradecanoyl phorbol 13
      acetate and PKC inhibitor bisindolylmaleimide reciprocally down- and up-regulate,
      respectively, TEF-mediated GGAATG core enhancer activity. In vitro TEF-1
      phosphorylation with several PKC isozymes and phosphoamino acid analysis
      confirmed that TEF-1 is a potential PKC substrate. TEF-1.DNA complexes formed by
      BeWo nuclear extracts are supershifted by phosphoserine- and phosphothreonine-
      but not phosphotyrosine-specific antibodies, indicating that TEF-1 is
      phosphorylated in vivo at serine and threonine residues. The TEF-1
      phosphorylation domain was localized to the third alpha-helix of the DNA binding
      domain and adjacent hinge region by phosphopeptide analysis. TEF-1
      phosphorylation significantly reduced its DNA binding activity both in vitro and
      in vivo, providing a possible mechanism for the inhibitory action of PKC.
      Finally, BeWo cells contained abundant levels of gamma and delta PKC isoforms,
      and their overexpression resulted in even greater inhibition of GGAATG core
      enhancer activity after 12-O-tetradecanoyl phorbol 13-acetate treatment. These
      data strongly suggest that PKC-mediated phosphorylation is a key factor
      controlling TEF function.

PMID- 11313340
TI  - cAmp regulation of arylalkylamine N-acetyltransferase (AANAT, EC 2.3.1.87): a new
      cell line (1E7) provides evidence of intracellular AANAT activation.
AB  - Arylalkylamine N-acetyltransferase (serotonin N-acetyltransferase, AANAT, EC ) is
      the penultimate enzyme in melatonin synthesis. As described here, a cell line
      (1E7) expressing human AANAT (hAANAT) has been developed to study the human
      enzyme. 1E7 hAANAT is detectable in immunoblots as a 23-kDa band and is
      immunocytochemically visualized in the cytoplasm. The specific concentration of
      hAANAT in homogenates is comparable to that of the night rat pineal gland.
      Kinetics of AANAT extracted from 1E7 cells are the same as those of bacterially
      expressed hAANAT; both preparations of hAANAT are equally sensitive to the
      inhibitor CoA-S-N-acetyltryptamine. Studies of cAMP regulation indicate that
      treatment with forskolin, dibutyryl cAMP, isobutylmethylxanthine, or
      isoproterenol activate cellular hAANAT within intact 1E7 cells approximately 8
      fold without markedly increasing the abundance of AANAT protein or the activity
      of AANAT in broken cell preparations; and, that forskolin, isobutylmethylxanthine
      and isoproterenol elevate cyclic AMP production. These observations extend our
      understanding of cAMP regulation of AANAT activity, because it is currently
      thought that this only involves changes in the steady-state levels of AANAT
      protein. This previously unrecognized switching mechanism could function
      physiologically to control melatonin production without changing AANAT protein
      levels.

PMID- 11313341
TI  - cDNA cloning and functional analysis of ascidian sperm proacrosin.
AB  - cDNA cloning and functional analysis of proacrosin from the ascidian Halocynthia
      roretzi were undertaken. The isolated cDNA of the ascidian preproacrosin consists
      of 2367 nucleotides, and an open reading frame encodes 505 amino acids, which
      corresponds to the molecular mass of 55,003 Da. The mRNA of proacrosin was found
      to be specifically expressed in the gonad by Northern blotting and in the
      spermatocytes or spermatids by in situ hybridization. The amino acid sequences
      around His(76), Asp(132), and Ser(227), which make up a catalytic triad, showed
      high homology to those of the trypsin family. Ascidian acrosin has paired basic
      residues (Lys(56)-His(57)) in the N-terminal region, which is one of the most
      characteristic features of mammalian acrosin. This region seems to play a key
      role in the binding of (pro)acrosin to the vitelline coat, because the peptide
      containing the paired basic residues, but not the peptide substituted with Ala,
      was capable of binding to the vitelline coat. Unlike mammalian proacrosin,
      ascidian proacrosin contains two CUB domains in the C-terminal region, in which
      CUB domain 1 seems to be involved in its binding to the vitelline coat. Four
      components of the vitelline coat that are capable of binding to CUB domain 1 in
      proacrosin were identified. In response to sperm activation, acrosin was released
      from sperm into the surrounding seawater, suggesting that ascidian acrosin plays
      a key role in sperm penetration through the coat. These results indicate that
      ascidian sperm contains a mammalian acrosin homologue, a multi-functional protein
      working in fertilization.

PMID- 11313342
TI  - Binding interactions between the active center cleft of recombinant pokeweed
      antiviral protein and the alpha-sarcin/ricin stem loop of ribosomal RNA.
AB  - Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein that
      catalytically cleaves a specific adenine base from the highly conserved alpha
      sarcin/ricin loop of the large ribosomal RNA, thereby inhibiting protein
      synthesis at the elongation step. Recently, we discovered that alanine
      substitutions of the active center cleft residues significantly impair the
      depurinating and ribosome inhibitory activity of PAP. Here we employed site
      directed mutagenesis combined with standard filter binding assays, equilibrium
      binding assays with Scatchard analyses, and surface plasmon resonance technology
      to elucidate the putative role of the PAP active center cleft in the binding of
      PAP to the alpha-sarcin/ricin stem loop of rRNA. Our findings presented herein
      provide experimental evidence that besides the catalytic site, the active center
      cleft also participates in the binding of PAP to the target tetraloop structure
      of rRNA. These results extend our recent modeling studies, which predicted that
      the residues of the active center cleft could, via electrostatic interactions,
      contribute to both the correct orientation and stable binding of the substrate
      RNA molecules in PAP active site pocket. The insights gained from this study also
      explain why and how the conserved charged and polar side chains located at the
      active center cleft of PAP and certain catalytic site residues, that do not
      directly participate in the catalytic deadenylation of ribosomal RNA, play a
      critical role in the catalytic removal of the adenine base from target rRNA
      substrates by affecting the binding interactions between PAP and rRNA.

PMID- 11313343
TI  - Hormone-induced conformational change of the purified soluble hormone binding
      domain of follitropin receptor complexed with single chain follitropin.
AB  - Human follicle-stimulating hormone receptor (hFSHR) belongs to family I of G
      protein-coupled receptors. FSHR extracellular domain (ECD) is predicted to have 8
      9 alphabeta or leucine-rich repeat motif elements. The objective of this study
      was to identify elements of the FSHR ECD involved in ligand binding.
      Preincubation of recombinant hFSHR ECD with rabbit antisera raised against
      synthetic peptides of hFSHR ECD primary sequence abolished follitropin binding
      primarily in the region of amino acids 150-254. Accessibility of hFSHR ECD after
      hormone binding, captured by monoclonal antibodies against either ECD or FSH, was
      decreased for the region of amino acids 150-220 but additionally for amino acids
      15-100. Thus, when hFSH bound first, accessibility of antibody binding was
      decreased to a much larger extent than if antibody was bound first. This
      suggestion of a conformational change upon binding was examined further. Circular
      dichroism spectra were recorded for purified single chain hFSH, hFSHR ECD, and
      hFSHR ECD-single chain hFSH complex. A spectral change indicated a small but
      consistent conformational change in the ECD.FSH complex after hormone binding.
      Taken together, these data demonstrate that FSH binding requires elements within
      the leucine-rich repeat motifs that form a central region of hFSHR ECD, and a
      conformational change occurs upon hormone binding.

PMID- 11313344
TI  - Yeast ERV2p is the first microsomal FAD-linked sulfhydryl oxidase of the
      Erv1p/Alrp protein family.
AB  - Saccharomyces cerevisiae Erv2p was identified previously as a distant homologue
      of Erv1p, an essential mitochondrial protein exhibiting sulfhydryl oxidase
      activity. Expression of the ERV2 (essential for respiration and vegetative growth
      2) gene from a high-copy plasmid cannot substitute for the lack of ERV1,
      suggesting that the two proteins perform nonredundant functions. Here, we show
      that the deletion of the ERV2 gene or the depletion of Erv2p by regulated gene
      expression is not associated with any detectable growth defects. Erv2p is located
      in the microsomal fraction, distinguishing it from the mitochondrial Erv1p.
      Despite their distinct subcellular localization, the two proteins exhibit
      functional similarities. Both form dimers in vivo and in vitro, contain a
      conserved YPCXXC motif in their carboxyl-terminal part, bind flavin adenine
      dinucleotide (FAD) as a cofactor, and catalyze the formation of disulfide bonds
      in protein substrates. The catalytic activity, the ability to form dimers, and
      the binding of FAD are associated with the carboxyl-terminal domain of the
      protein. Our findings identify Erv2p as the first microsomal member of the
      Erv1p/Alrp protein family of FAD-linked sulfhydryl oxidases. We propose that
      Erv2p functions in the generation of microsomal disulfide bonds acting in
      parallel with Ero1p, the essential, FAD-dependent oxidase of protein disulfide
      isomerase.

PMID- 11313345
TI  - Connexin45 interacts with zonula occludens-1 and connexin43 in osteoblastic
      cells.
AB  - The relative expression of connexin43 and connexin45 modulates gap junctional
      communication and production of bone matrix proteins in osteoblastic cells. It is
      likely that changes in gap junction permeability are determined by the
      interaction between these two proteins. Cx43 interacts with ZO-1, which may be
      involved in trafficking of Cx43 or facilitating interactions between Cx43 and
      other proteins. In this study we sought to identify proteins that associate with
      Cx45 by coprecipitation in non-denaturing conditions. Cx45 was isolated with a
      220-kDa protein that we identified as ZO-1. Under the same conditions, Cx43 also
      was isolated with anti-Cx45 antiserum from Cx45-transfected ROS cells (ROS/Cx45
      cells). Cx43 antiserum could also coprecipitate ZO-1 in the transfected and
      untransfected ROS cells. Double label immunofluorescence studies showed that ZO
      1, Cx43, and Cx45 colocalized at appositional membranes in ROS/Cx45 cells
      suggesting that all three proteins are normally associated in the cells.
      Additionally, we found that in vitro translated ZO-1 binds to the carboxyl
      terminal of Cx45 indicating that there is a direct interaction between the
      carboxyl-terminal of Cx45 and ZO-1. These studies demonstrate that ZO-1 interacts
      with Cx45 as well as with Cx43, and suggest that the interaction of connexins
      with ZO-1 may play a role in regulating the composition of the gap junction and
      may modulate connexin-connexin interactions.

PMID- 11313346
TI  - Regulation of the 75-kDa subunit of mitochondrial complex I by iron.
AB  - Iron homeostasis is tightly regulated, as cells work to conserve this essential
      but potentially toxic metal. The translation of many iron proteins is controlled
      by the binding of two cytoplasmic proteins, iron regulatory protein 1 and 2 (IRP1
      and IRP2) to stem loop structures, known as iron-responsive elements (IREs),
      found in the untranslated regions of their mRNAs. In short, when iron is
      depleted, IRP1 or IRP2 bind IREs; this decreases the synthesis of proteins
      involved in iron storage and mitochondrial metabolism (e.g. ferritin and
      mitochondrial aconitase) and increases the synthesis of those involved in iron
      uptake (e.g. transferrin receptor). It is likely that more iron-containing
      proteins have IREs and that other IRPs may exist. One obvious place to search is
      in Complex I of the mitochondrial respiratory chain, which contains at least 6
      iron-sulfur (Fe-S) subunits. Interestingly, in idiopathic Parkinson's disease,
      iron homeostasis is altered, and Complex I activity is diminished. These findings
      led us to investigate whether iron status affects the Fe-S subunits of Complex I.
      We found that the protein levels of the 75-kDa subunit of Complex I were
      modulated by levels of iron in the cell, whereas mRNA levels were minimally
      changed. Isolation of a clone of the 75-kDa Fe-S subunit with a more complete 5'
      untranslated region sequence revealed a novel IRE-like stem loop sequence. RNA
      protein gel shift assays demonstrated that a specific cytoplasmic protein bound
      the novel IRE and that the binding of the protein was affected by iron status.
      Western blot analysis and supershift assays showed that this cytosolic protein is
      neither IRP1 nor IRP2. In addition, ferritin IRE was able to compete for binding
      with this putative IRP. These results suggest that the 75-kDa Fe-S subunit of
      mitochondrial Complex I may be regulated by a novel IRE-IRP system.

PMID- 11313347
TI  - Different mechanisms of the binding of soluble electron donors to the
      photosynthetic reaction center of Rubrivivax gelatinosus and Blastochloris
      viridis.
AB  - The tetraheme cytochrome subunits of the photosynthetic reaction centers (RCs) in
      two species of purple bacteria, Rubrivivax gelatinosus and Blastochloris
      (Rhodopseudomonas) viridis, were compared in terms of their capabilities to bind
      different electron-donor proteins. The wild-type RCs from both species and
      mutated forms of R. gelatinosus RCs (with amino acid substitutions introduced to
      the binding domain for electron-donor proteins) were tested for their reactivity
      with soluble cytochromes and high potential iron-sulfur protein. Cytochromes from
      both species were good electron donors to the B. viridis RC and the R.
      gelatinosus RC. The reactivity in the R. gelatinosus RC showed a clear dependence
      on the polarity of the charges introduced to the binding domain, indicating the
      importance of the electrostatic interactions. In contrast, high potential iron
      sulfur protein, presumed to operate according to the hydrophobic mechanism of
      binding, reacted significantly only with the R. gelatinosus RC. Evolutionary
      substitution of amino acids in a region of the binding domain on the cytochrome
      subunit surface probably caused the change in the principal mode of protein
      protein interactions in the electron-transfer chains.

PMID- 11313348
TI  - Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide
      production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium
      in response to B16 melanoma adhesion in vitro.
AB  - The mechanism of NO- and H(2)O(2)-induced tumor cytotoxicity was examined during
      B16 melanoma (B16M) adhesion to the hepatic sinusoidal endothelium (HSE) in
      vitro. We used endothelial nitric-oxide synthetase gene disruption and N(G)-nitro
      l-arginine methyl ester-induced inhibition of nitric-oxide synthetase activity to
      study the effect of HSE-derived NO on B16M cell viability. Extracellular H(2)O(2)
      was removed by exogenous catalase. H(2)O(2) was not cytotoxic in the absence of
      NO. However, NO-induced tumor cytotoxicity was increased by H(2)O(2) due to the
      formation of potent oxidants, likely ( small middle dot)OH and (-)OONO radicals,
      via a trace metal-dependent process. B16M cells cultured to low density (LD
      cells), with high GSH content, were more resistant to NO and H(2)O(2) than B16M
      cells cultured to high density (HD cells; with approximately 25% of the GSH
      content found in LD cells). Resistance of LD cells decreased using buthionine
      sulfoximine, a specific GSH synthesis inhibitor, whereas resistance increased in
      HD cells using GSH ester, which delivers free intracellular GSH. Because NO and
      H(2)O(2) were particularly cytotoxic in HD cells, we investigated the enzyme
      activities that degrade H(2)O(2). NO and H(2)O(2) caused an approximately 75% (LD
      cells) and a 60% (HD cells) decrease in catalase activity without affecting the
      GSH peroxidase/GSH reductase system. Therefore, B16M resistance to the HSE
      induced cytotoxicity appears highly dependent on GSH and GSH peroxidase, which
      are both required to eliminate H(2)O(2). In agreement with this fact, ebselen, a
      GSH peroxidase mimic, abrogated the increase in NO toxicity induced by H(2)O(2).

PMID- 11313349
TI  - Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3
      domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells.
AB  - ADAM 12, a member of the ADAM family of transmembrane metalloprotease
      disintegrins, has been implicated previously in the differentiation of skeletal
      myoblasts. In the present study, we show that the cytoplasmic tail of mouse ADAM
      12 interacts in vitro and in vivo with the Src homology 3 domain of the p85alpha
      regulatory subunit of phosphatidylinositol (PI) 3-kinase. By site-directed
      mutagenesis, we have identified three p85alpha-binding sites in ADAM 12 involving
      PXXP motifs located at amino acids 825-828, 833-836, and 884-887. Using green
      fluorescent protein (GFP)-pleckstrin homology (PH) domain fusion protein as a
      probe for PI 3-kinase lipid products, we have further demonstrated that
      expression of ADAM 12 in C2C12 cells resulted in translocation of GFP-PH to the
      plasma membrane. This suggests that transmembrane ADAM 12, by providing docking
      sites for the Src homology 3 domain of p85alpha, activates PI 3-kinase by
      mediating its recruitment to the membrane. Because PI 3-kinase is critical for
      terminal differentiation of myoblasts, and because expression of ADAM 12 is up
      regulated at the onset of the differentiation process, ADAM 12-mediated
      activation may constitute one of the regulatory mechanisms for PI 3-kinase during
      myoblast differentiation.

PMID- 11313351
TI  - Renal tubule-specific transcription and chromosomal localization of rat thiazide
      sensitive Na-Cl cotransporter gene.
AB  - The molecular mechanism underlying the renal expression localization of the
      thiazide-sensitive Na-Cl cotransporter (TSC) gene was studied. The TSC gene was
      localized to chromosome 19p12-14. In cultured cells, tissue-specific
      transcription activity of the 5'-flanking region of the rat rTSC gene (5'FL/rTSC)
      was demonstrated, and the major promoter region was located between position -580
      and -141. To further examine the tissue-specific transcription, transgenic rats
      harboring the 5'FL/rTSC fused upstream of the LacZ gene were generated.
      Immunohistochemical analysis clearly showed that LacZ gene expression was co
      localized to distal convoluted tubules (DCT) with TSC, indicating that the
      5'FL/rTSC regulates the renal tubule-specific TSC expression. Because a
      transcription factor, HFH-3 (hepatocyte nuclear factor-3/folk head homologue-3),
      had also been localized to DCT, a possible role of the putative cis-acting
      element (HFH-3/rTSC, -400/-387 position) for HFH-3 binding in the tissue-specific
      transcription was examined. Deletion and mutation analyses suggested that
      transcription of the HFH-3/rTSC was actually responsive to HFH-3, and
      electrophoretic mobility shift assay showed a direct binding of in vitro
      synthesized HFH-3 to the HFH-3/rTSC. In conclusion, the rTSC gene is localized to
      rat chromosome 19p12--24. The transcription regulatory region of the TSC gene
      confers DCT-specific gene expression. DCT-specific transcription factor HFH-3 may
      be involved in the renal tubule-specific transcription of TSC gene.

PMID- 11313352
TI  - The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus
      transactivates the telomerase reverse transcriptase promoter.
AB  - Telomerase is a multi-subunit ribonucleoprotein holoenzyme that stabilizes
      telomere length through the addition of new repeat sequence to the ends of
      chromosomes. Telomerase reverse transcriptase is the subunit of this complex
      responsible for the enzymatic activity of telomerase. Expression of the reverse
      transcriptase is regulated at the level of transcription through the action of
      transcription factors that target its promoter. Most Kaposi's sarcoma tumor cells
      are latently infected with the Kaposi's sarcoma-associated herpesvirus, and the
      constitutive expression of a viral-encoded latency-associated nuclear antigen has
      been shown to be important for the maintenance of the viral episome. The
      proliferative nature of Kaposi's sarcoma suggests that this antigen may also play
      a critical role in viral-mediated oncogenesis. In this study telomerase reverse
      transcriptase promoter elements cloned into a luciferase reporter plasmid were
      analyzed to determine the ability of the latency-associated nuclear antigen to
      regulate transcription. The latency-associated nuclear antigen transactivated the
      full-length promoter in 293T, 293, and BJAB cell lines. Furthermore, truncation
      promoter studies implicated sequence from -130 to +5 in viral-mediated
      activation. This region contains five Sp1 transcription factor-binding sites.
      Electrophoretic mobility shift assays indicated that the latency-associated
      nuclear antigen targets and affects the Sp1-DNA complex in the context of BJAB
      nuclear extracts.

PMID- 11313353
TI  - Characterization of Inherited Differences in Transcription of the Human Integrin
      alpha 2 Gene.
AB  - Inherited, single-base substitutions are found at only two positions, C(-)52T and
      C(-)92G, within the proximal 5'-regulatory region (within -1096 to +48) of the
      human integrin alpha(2) gene. We recently reported that the T(-)52 substitution
      results in decreased binding of transcription factor Sp1 to adjacent binding
      sites, decreased transcription of the alpha(2) gene, and reduced densities of
      platelet alpha(2)beta(1). In this study, we identify an additional Sp1-binding
      site at position -107 to -99 and show that the adjacent dimorphic sequence C(
      )92G also influences the rate of gene transcription. In the erythroleukemia cell
      line Dami, transfected promoter-luciferase constructs bearing the G(-)92 sequence
      exhibit roughly a 3-fold decrease in activity relative to the C(-)92 constructs.
      In transfected CHRF-288-11 megakaryocytic cells, the corresponding activity
      decreases by 5-fold. DNase I footprinting of the promoter region with Dami
      nuclear extracts showed a protected segment at -107 to -99 that can be
      deprotected by coincubation with molar excess of a consensus Sp1 oligonucleotide.
      Gel mobility shift assays and supershift assays with specific antibodies indicate
      that Sp1 binds to this region of the alpha(2) gene promoter. Mutation of the Sp1
      binding element within -107 to -99 in constructs containing either C(-)92 or G(
      )92 abolishes basal promoter activity and eliminates the binding of Sp1. The G(
      )92 sequence has a gene frequency of 0.15 in a typical Caucasian population, and
      the presence of this allele correlates with reduced densities of platelet
      alpha(2)beta(1). The combined substitution G(-)92/T(-)52 has an additive
      influence on gene transcription, resulting in an 8-fold decrease in transfected
      Dami cells or a 20-fold decrease in transfected CHRF-288-11 cells. In summary,
      the natural dimorphism C(-)92G within the proximal 5'-regulatory region of the
      human integrin alpha(2) gene contributes to the regulation of integrin
      alpha(2)beta(1) expression on megakaryocytes and blood platelets and must thereby
      modulate collagen-related platelet function in vivo.

PMID- 11313354
TI  - Human alveolar macrophages and granulocyte-macrophage colony-stimulating factor
      induced monocyte-derived macrophages are resistant to H2O2 via their high basal
      and inducible levels of catalase activity.
AB  - Human alveolar macrophages (A-MPhi) and macrophages (MPhi) generated from human
      monocytes under the influence of granulocyte-macrophage colony-stimulating
      factors (GM-MPhi) express high levels of catalase activity and are highly
      resistant to H(2)O(2). In contrast, MPhi generated from monocytes by macrophage
      colony-stimulating factors (M-MPhi) express low catalase activity and are about
      50-fold more sensitive to H(2)O(2) than GM-MPhi or A-MPhi. Both A-MPhi and GM
      MPhi but not M-MPhi can induce catalase expression in both protein and mRNA
      levels when stimulated with H(2)O(2) or zymosan. M-MPhi but not GM-MPhi produce a
      large amount of H(2)O(2) in response to zymosan or heat-killed Staphylococcus
      aureus. These findings indicate that GM-MPhi and A-MPhi but not M-MPhi are strong
      scavengers of H(2)O(2) via the high basal level of catalase activity and a marked
      ability of catalase induction and that catalase activity of MPhi is regulated by
      colony-stimulating factors during differentiation.

PMID- 11313355
TI  - Identification of genes encoding adenylate isopentenyltransferase, a cytokinin
      biosynthesis enzyme, in Arabidopsis thaliana.
AB  - The initial step in the de novo biosynthesis of cytokinin in higher plants is the
      formation of isopentenyladenosine 5'-monophosphate (iPMP) from AMP and
      dimethylallylpyrophosphate (DMAPP), which is catalyzed by adenylate
      isopentenyltransferase (IPT). Although cytokinin is an essential hormone for
      growth and development, the nature of the enzyme for its biosynthesis in higher
      plants has not been identified. Herein, we describe the molecular cloning and
      biochemical identification of IPTs from Arabidopsis thaliana. Eight cDNAs
      encoding putative IPT, designated as AtIPT1 to AtIPT8, were picked up from A.
      thaliana. The Escherichia coli transformants expressing the recombinant proteins
      excreted cytokinin species into the culture medium except for that expressing
      AtIPT2 that is a putative tRNA IPT. A purified recombinant AtIPT1 catalyzed the
      formation of iPMP from DMAPP and AMP. These results indicate that the small
      multigene family contains both types of isopentenyltransferase, which could
      synthesize cytokinin and mature tRNA.

PMID- 11313356
TI  - Functional significance of the beta hairpin in the insecticidal neurotoxin omega
      atracotoxin-Hv1a.
AB  - omega-Atracotoxin-Hv1a is an insect-specific neurotoxin whose phylogenetic
      specificity derives from its ability to antagonize insect, but not vertebrate,
      voltage-gated calcium channels. In order to help understand its mechanism of
      action and to enhance its utility as a lead compound for insecticide development,
      we used a combination of protein engineering and site-directed mutagenesis to
      probe the toxin for key functional regions. First, we constructed a Hairpinless
      mutant in which the C-terminal beta-hairpin, which is highly conserved in this
      family of neurotoxins, was excised without affecting the fold of the residual
      disulfide-rich core of the toxin. The Hairpinless mutant was devoid of
      insecticidal activity, indicating the functional importance of the hairpin. We
      subsequently developed a highly efficient system for production of recombinant
      toxin and then probed the hairpin for key functional residues using alanine
      scanning mutagenesis followed by a second round of mutagenesis based on initial
      "hits" from the alanine scan. This revealed that two spatially proximal residues,
      Asn(27) and Arg(35), form a contiguous molecular surface that is essential for
      toxin activity. We propose that this surface of the beta-hairpin is a key site
      for interaction of the toxin with insect calcium channels.

PMID- 11313357
TI  - Differential assembly of rat purinergic P2X7 receptor in immune cells of the
      brain and periphery.
AB  - ATP-gated P2X(7) purinoceptors are found in most immune cells of the periphery
      and the brain where their activation leads to multiple downstream events such as
      cell permeabilization, apoptosis, and/or cytokine release. P2X(7) receptors do
      not form heteromeric receptors with any of the other six P2X subunits, and it is
      not known what type of homomeric assemblies the P2X(7) subunit makes. We
      constructed and purified an ectodomain protein of the rat P2X(7) receptor (amino
      acids 60-323) and used this to generate a monoclonal antibody (Ab) with which to
      probe P2X(7) receptors in central and peripheral immune cells. In HEK cells
      expressing rat P2X(7) receptors, the Ab increased the maximum current evoked by
      BzATP by 3-8-fold with a 5-fold leftward shift in EC(50) concentration. This Ab
      recognized only a non-denatured, multimeric form of the receptor on blue native
      PAGE but did not recognize the denatured form on SDS-PAGE. A C-terminal
      polyclonal P2X(7) Ab recognized both monomeric subunits on SDS-PAGE and a
      multimeric complex on blue native-PAGE in this heterologous expression system.
      With Western blotting using these two Abs, native P2X(7) receptors in peritoneal
      macrophage and bone marrow cells are shown to exist as a strongly bound
      multimeric complex, whereas P2X(7) receptors in brain glia and/or astrocytes
      appear to form only as monomeric subunits.

PMID- 11313358
TI  - Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-mannoheptose
      6-epimerase.
AB  - ADP-L-glycero-D-mannoheptose 6-epimerase is required for lipopolysaccharide inner
      core biosynthesis in several genera of Gram-negative bacteria. The enzyme
      contains both fingerprint sequences Gly-X-Gly-X-X-Gly and Gly-X-X-Gly-X-X-Gly
      near its N terminus, which is indicative of an ADP binding fold. Previous studies
      of this ADP-l-glycero-D-mannoheptose 6-epimerase (ADP-hep 6-epimerase) were
      consistent with an NAD(+) cofactor. However, the crystal structure of this ADP
      hep 6-epimerase showed bound NADP (Deacon, A. M., Ni, Y. S., Coleman, W. G., Jr.,
      and Ealick, S. E. (2000) Structure 5, 453-462). In present studies, apo-ADP-hep 6
      epimerase was reconstituted with NAD(+), NADP(+), and FAD. In this report we
      provide data that shows NAD(+) and NADP(+) both restored enzymatic activity, but
      FAD could not. Furthermore, ADP-hep 6-epimerase exhibited a preference for
      binding of NADP(+) over NAD(+). The K(d) value for NADP(+) was 26 microm whereas
      that for NAD(+) was 45 microm. Ultraviolet circular dichroism spectra showed that
      apo-ADP-hep 6-epimerase reconstituted with NADP(+) had more secondary structure
      than apo-ADP-hep 6-epimerase reconstituted with NAD(+). Perchloric acid extracts
      of the purified enzyme were assayed with NAD(+)-specific alcohol dehydrogenase
      and NADP(+)-specific isocitric dehydrogenase. A sample of the same perchloric
      acid extract was analyzed in chromatographic studies, which demonstrated that ADP
      hep 6-epimerase binds NADP(+) in vivo. A structural comparison of ADP-hep 6
      epimerase with UDP-galactose 4-epimerase, which utilizes an NAD(+) cofactor, has
      identified the regions of ADP-hep 6-epimerase, which defines its specificity for
      NADP(+).

PMID- 11313359
TI  - Multiple bone morphogenetic protein 1-related mammalian metalloproteinases
      process pro-lysyl oxidase at the correct physiological site and control lysyl
      oxidase activation in mouse embryo fibroblast cultures.
AB  - Lysyl oxidase catalyzes the final enzymatic step required for collagen and
      elastin cross-linking in extracellular matrix biosynthesis. Pro-lysyl oxidase is
      processed by procollagen C-proteinase activity, which also removes the C
      propeptides of procollagens I-III. The Bmp1 gene encodes two procollagen C
      proteinases: bone morphogenetic protein 1 (BMP-1) and mammalian Tolloid (mTLD).
      Mammalian Tolloid-like (mTLL)-1 and -2 are two genetically distinct BMP-1-related
      proteinases, and mTLL-1 has been shown to have procollagen C-proteinase activity.
      The present study is the first to directly compare pro-lysyl oxidase processing
      by these four related proteinases. In vitro assays with purified recombinant
      enzymes show that all four proteinases productively cleave pro-lysyl oxidase at
      the correct physiological site but that BMP-1 is 3-, 15-, and 20-fold more
      efficient than mTLL-1, mTLL-2, and mTLD, respectively. To more directly assess
      the roles of BMP-1 and mTLL-1 in lysyl oxidase activation by connective tissue
      cells, fibroblasts cultured from Bmp1-null, Tll1-null, and Bmp1/Tll1 double null
      mouse embryos, thus lacking BMP-1/mTLD, mTLL-1, or all three enzymes,
      respectively, were assayed for lysyl oxidase enzyme activity and for accumulation
      of pro-lysyl oxidase and mature approximately 30-kDa lysyl oxidase. Wild type
      cells or cells singly null for Bmp1 or Tll1 all produced both pro-lysyl oxidase
      and processed lysyl oxidase at similar levels, indicating apparently normal
      levels of processing, consistent with enzyme activity data. In contrast, double
      null Bmp1/Tll1 cells produced predominantly unprocessed 50-kDa pro-lysyl oxidase
      and had lysyl oxidase enzyme activity diminished by 70% compared with wild type,
      Bmp1-null, and Tll1-null cells. Thus, the combination of BMP-1/mTLD and mTLL-1 is
      shown to be responsible for the majority of processing leading to activation of
      lysyl oxidase by murine embryonic fibroblasts, whereas in vitro studies identify
      pro-lysyl oxidase as the first known substrate for mTLL-2.

PMID- 11313360
TI  - Signal transduction in eclosion hormone-induced secretion of ecdysis-triggering
      hormone.
AB  - Inka cells of insect epitracheal glands (EGs) secrete preecdysis and ecdysis
      triggering hormones (PETH and ETH) at the end of each developmental stage. Both
      peptides act in the central nervous system to evoke the ecdysis behavioral
      sequence, a stereotype behavior during which old cuticle is shed. Secretion of
      ETH is stimulated by a brain neuropeptide, eclosion hormone (EH). EH evokes
      accumulation of cGMP followed by release of ETH from Inka cells, and exogenous
      cGMP evokes secretion of ETH. The secretory responses to EH and cGMP are
      inhibited by the broad-spectrum kinase inhibitor staurosporine, and the response
      to EH is potentiated by the phosphatase inhibitor calyculin A. Staurosporine did
      not inhibit EH-evoked accumulation of cGMP. Changes in cytoplasmic Ca2+ in Inka
      cells during EH signaling were monitored via fluorescence ratioing with fura-2
      loaded EGs. Cytoplasmic Ca2+ increases within 30-120 s after addition of EH to
      EGs, and it remains elevated for at least 10 min, corresponding with the time
      course of secretion. Secretion is increased in dose-dependent manner by the Ca2+
      ATPase inhibitor thapsigargin, a treatment that does not elevate glandular cGMP
      above basal levels. The secretory response to EH is partially inhibited in glands
      loaded with EGTA, while cGMP levels are unaffected. These findings suggest that
      EH activates second messenger cascades leading to cGMP accumulation and Ca2+
      mobilization and/or influx and that both pathways are required for a full
      secretory response. cGMP activates a staurosporine-inhibitable protein kinase. We
      propose that Ca2+ acts via a parallel cascade with a time course that is similar
      to that for cGMP activation of a cGMP-dependent protein kinase.

PMID- 11313361
TI  - TIP47 is not a component of lipid droplets.
AB  - TIP47 functions in the delivery of mannose 6-phosphate receptors from endosomes
      to the trans-Golgi network both in vitro and in vivo. It binds directly and very
      specifically to the cytoplasmic domains of both the cation-independent and cation
      dependent mannose 6-phosphate receptors. TIP47 is 43% identical to a lipid
      droplet-associated protein named adipophilin; much of the identity resides near
      the N termini of these proteins. It was recently reported in this journal, in a
      study using antiserum from this laboratory, that TIP47 is a constituent of lipid
      droplets (Wolins, N. E., Rubin, B., and Brasaemle, D. L. (2001) J. Biol. Chem.
      276, 5101-5108). We show here that the findings of Wolins et al. were likely due
      to either a cross-reactive, unidentified protein in HeLa cells that is recognized
      by our antiserum and/or the fact that our serum also cross-reacts with the
      adipophilin protein itself, shown directly by expression of adipophilin in
      Escherichia coli. Using antibodies specific for residues 152-434 of TIP47, we
      show that TIP47 is not a constituent of lipid droplets.

PMID- 11313362
TI  - A unique multifunctional transporter translocates estradiol-17beta -glucuronide
      in rat liver microsomal vesicles.
AB  - A wide array of drugs, xenobiotics, and endogenous compounds undergo
      detoxification by conjugation with glucuronic acid in the liver via the action of
      UDP-glucuronosyltransferases. The mechanism whereby glucuronides, generated by
      this enzyme system in the lumen of the endoplasmic reticulum (ER), are exported
      to the cytosol prior to excretion is unknown. We examined this process in
      purified rat liver microsomes using a rapid filtration technique and
      [(3)H]estradiol-17beta-d-glucuronide ([(3)H]E(2)17betaG) as model substrate. Time
      dependent uptake of intact [(3)H]E(2)17betaG was observed and shrinkage of ER
      vesicles by raffinose lowered the steady-state level of [(3)H]E(2)17betaG
      accumulation. In addition, rapid efflux of [(3)H]E(2)17betaG from rat liver
      microsomal vesicles suggested that the transport process is bidirectional.
      Microsomal uptake was saturable with an apparent K(m) and V(max) of 3.29 +/- 0.58
      microm and 0.19 +/- 0.02 nmol.min(-1).mg protein(-1), respectively. Transport of
      [(3)H]E(2)17betaG was inhibited by the anion transport inhibitors 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid and probenecid. Specificity of the
      transport process was investigated by studying the cis-inhibitory effect of
      anionic metabolites, as well as substrates of the plasma membrane multidrug
      resistance-associated proteins on the uptake of [(3)H]E(2)17betaG. Collectively,
      these data are indicative of a novel multifunctional and bidirectional protein
      carrier for E(2)17betaG and other anionic compounds in the hepatic ER. This
      intracellular membrane transporter may contribute to the phenomenon of multidrug
      resistance.

PMID- 11313363
TI  - Chimeras of nitric-oxide synthase types I and III establish fundamental
      correlates between heme reduction, heme-NO complex formation, and catalytic
      activity.
AB  - Neuronal nitric-oxide synthase (nNOS or NOS I) and endothelial NOS (eNOS or NOS
      III) differ widely in their reductase and nitric oxide (NO) synthesis activities,
      electron transfer rates, and propensities to form a heme-NO complex during
      catalysis. We generated chimeras by swapping eNOS and nNOS oxygenase domains to
      understand the basis for these differences and to identify structural elements
      that determine their catalytic behaviors. Swapping oxygenase domains did not
      alter domain-specific catalytic functions (cytochrome c reduction or H(2)O(2)
      supported N(omega)-hydroxy-l-arginine oxidation) but markedly affected steady
      state NO synthesis and NADPH oxidation compared with native eNOS and nNOS.
      Stopped-flow analysis showed that reductase domains either maintained (nNOS) or
      slightly exceeded (eNOS) their native rates of heme reduction in each chimera.
      Heme reduction rates were found to correlate with the initial rates of NADPH
      oxidation and heme-NO complex formation, with the percentage of heme-NO complex
      attained during the steady state, and with NO synthesis activity. Oxygenase
      domain identity influenced these parameters to a lesser degree. We conclude: 1)
      Heme reduction rates in nNOS and eNOS are controlled primarily by their reductase
      domains and are almost independent of oxygenase domain identity. 2) Heme
      reduction rate is the dominant parameter controlling the kinetics and extent of
      heme-NO complex formation in both eNOS and nNOS, and thus it determines to what
      degree heme-NO complex formation influences their steady-state NO synthesis,
      whereas oxygenase domains provide minor but important influences. 3) General
      principles that relate heme reduction rate, heme-NO complex formation, and NO
      synthesis are not specific for nNOS but apply to eNOS as well.

PMID- 11313364
TI  - A Gal4-sigma 54 hybrid protein that functions as a potent activator of RNA
      polymerase II transcription in yeast.
AB  - The bacterial final sigma(54) protein associates with core RNA polymerase to form
      a holoenzyme complex that renders cognate promoters enhancer-dependent. Although
      unusual in bacteria, enhancer-dependent transcription is the paradigm in
      eukaryotes. Here we report that a fragment of Escherichia coli final sigma(54)
      encompassing amino acid residues 29-177 functions as a potent transcriptional
      activator in yeast when fused to a Gal4 DNA binding domain. Activation by Gal4
      final sigma(54) is TATA-dependent and requires the SAGA coactivator complex,
      suggesting that Gal4-final sigma(54) functions by a normal mechanism of
      transcriptional activation. Surprisingly, deletion of the AHC1 gene, which
      encodes a polypeptide unique to the ADA coactivator complex, stimulates Gal4
      final sigma(54)-mediated activation and enhances the toxicity of Gal4-final
      sigma(54). Accordingly, the SAGA and ADA complexes, both of which include Gcn5 as
      their histone acetyltransferase subunit, exert opposite effects on
      transcriptional activation by Gal4-final sigma(54). Gal4-final sigma(54)
      activation and toxicity are also dependent upon specific final sigma(54) residues
      that are required for activator-responsive promoter melting by final sigma(54) in
      bacteria, implying that activation is a consequence of final sigma(54)-specific
      features rather than a structurally fortuitous polypeptide fragment. As such,
      Gal4-final sigma(54) represents a novel tool with the potential to provide
      insight into the mechanism by which natural activators function in eukaryotic
      cells.

PMID- 11313365
TI  - Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked
      kinase: critical roles for kinase activity and amino acids arginine 211 and
      serine 343.
AB  - Protein kinase B (PKB/Akt) is a regulator of cell survival and apoptosis. To
      become fully activated, PKB/Akt requires phosphorylation at two sites, threonine
      308 and serine 473, in a phosphatidylinositol (PI) 3-kinase-dependent manner. The
      kinase responsible for phosphorylation of threonine 308 is the PI 3-kinase
      dependent kinase-1 (PDK-1), whereas phosphorylation of serine 473 has been
      suggested to be regulated by PKB/Akt autophosphorylation in a PDK-1-dependent
      manner. However, the integrin-linked kinase (ILK) has also been shown to regulate
      phosphorylation of serine 473 in a PI 3-kinase-dependent manner. Whether ILK
      phosphorylates this site directly or functions as an adapter molecule has been
      debated. We now show by in-gel kinase assay and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry that biochemically purified ILK can
      phosphorylate PKB/Akt directly. Co-immunoprecipitation analysis of cell extracts
      demonstrates that ILK can complex with PKB/Akt as well as PDK-1 and that ILK can
      disrupt PDK-1/PKB association. The amino acid residue serine 343 of ILK within
      the activation loop is required for kinase activity as well as for its
      interaction with PKB/Akt. Mutational analysis of ILK further shows a crucial role
      for arginine 211 of ILK within the phosphoinositide phospholipid binding domain
      in the regulation of PKB- serine 473 phosphorylation. A highly selective small
      molecule inhibitor of ILK activity also inhibits the ability of ILK to
      phosphorylate PKB/Akt in vitro and in intact cells. These data demonstrate that
      ILK is an important upstream kinase for the regulation of PKB/Akt.

PMID- 11313366
TI  - Human intelectin is a novel soluble lectin that recognizes galactofuranose in
      carbohydrate chains of bacterial cell wall.
AB  - Galactofuranosyl residues are present in various microorganisms but not in
      mammals. In this study, we identified a human lectin binding to galactofuranosyl
      residues and named this protein human intelectin (hIntL). The mature hIntL was a
      secretory glycoprotein consisting of 295 amino acids and N-linked
      oligosaccharides, and its basic structural unit was a 120-kDa homotrimer in which
      40-kDa polypeptides were bridged by disulfide bonds. The hIntL gene was split
      into 8 exons on chromosome 1q21.3, and hIntL mRNA was expressed in the heart,
      small intestine, colon, and thymus. hIntL showed high levels of homology with
      mouse intelectin, Xenopus laevis cortical granule lectin/oocyte lectin, lamprey
      serum lectin, and ascidian galactose-specific lectin. These homologues commonly
      contained no carbohydrate recognition domain, which is a characteristic of C-type
      lectins, although some of them have been reported as Ca(2+)-dependent lectins.
      Recombinant hIntL revealed affinities to d-pentoses and a d-galactofuranosyl
      residue in the presence of Ca(2+), and recognized the bacterial arabinogalactan
      of Nocardia containing d-galactofuranosyl residues. These results suggested that
      hIntL is a new type lectin recognizing galactofuranose, and that hIntL plays a
      role in the recognition of bacteria-specific components in the host.

PMID- 11313367
TI  - Cutting edge: intravenous soluble antigen is presented to CD4 T cells by CD8-
      dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells.
AB  - Mouse spleen contains three distinct mature dendritic cell (DC) populations
      (CD4(+)8(-), CD4(-)8(-), and CD4(-)8(+)) which retain a capacity to take up
      particulate and soluble AGS: Although the three splenic DC subtypes showed
      similar uptake of injected soluble OVA, they differed markedly in their capacity
      to present this Ag and activate proliferation in OVA-specific CD4 or CD8 T cells.
      For class II MHC-restricted presentation to CD4 T cells, the CD8(-) DC subtypes
      were more efficient, but for class I MHC-restricted presentation to CD8 T cells,
      the CD8(+) DC subtype was far more effective. This differential persisted when
      the DC were activated with LPS. The CD8(+) DC are therefore specialized for in
      vivo cross-presentation of exogenous soluble Ags into the class I MHC
      presentation pathway.

PMID- 11313368
TI  - Cutting edge: distinct motifs within CD28 regulate T cell proliferation and
      induction of Bcl-XL.
AB  - CD28 provides an important costimulatory signal in T cell activation that
      regulates multiple cellular processes including proliferation and survival.
      Several signal transduction pathways are activated by CD28; however, the precise
      biochemical mechanism by which CD28 regulates T cell function remains
      controversial. Retroviral gene transfer into primary T cells from TCR-transgenic,
      CD28-deficient mice was used to determine the specific sequences within CD28 that
      determine function. Discrete regions of the cytoplasmic domain of CD28 were
      identified that differentially regulate T cell proliferation and induction of the
      anti-apoptotic protein Bcl-X(L). Mutation of C-terminal proline residues
      abrogated the proliferative and cytokine regulatory features of CD28
      costimulation while preserving Bcl-X(L) induction. Conversely, mutation of
      residues important in phosphatidylinositol 3-kinase activation partially
      inhibited proliferation but prevented induction of Bcl-X(L.) Thus the ability of
      CD28 to regulate proliferation and induction of Bcl-X(L) map to distinct motifs,
      suggesting independent signaling cascades modulate these biologic effects.

PMID- 11313369
TI  - The role of NF-kappa B in TNF-related apoptosis-inducing ligand (TRAIL)-induced
      apoptosis of melanoma cells.
AB  - Previous studies have shown that activation of NF-kappaB can inhibit apoptosis
      induced by a number of stimuli. It is also known that TNF-related apoptosis
      inducing ligand (TRAIL) can activate NF-kappaB through the death receptors TRAIL
      R1 and TRAIL-R2, and decoy receptor TRAIL-R4. In view of these findings, we have
      investigated the extent to which activation of NF-kappaB may account for the
      variable responses of melanoma lines to apoptosis induced by TRAIL and other TNF
      family members. Pretreatment of the melanoma lines with the proteasome inhibitor
      N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (LLnL), which is known to inhibit
      activation of NF-kappaB, was shown to markedly increase apoptosis in 10 of 12
      melanoma lines with death receptors for TRAIL. The specificity of results for
      inhibition of NF-kappaB activation was supported by an increase of TRAIL-induced
      apoptosis in melanoma cells transfected with a degradation-resistant
      IkappaBalpha. Furthermore, studies with NF-kappaB reporter constructs revealed
      that the resistance of melanoma lines to TRAIL-induced apoptosis was correlated
      to activation of NF-kappaB in response to TRAIL. TRAIL-resistant sublines that
      were generated by intermittent exposure to TRAIL were shown to have high levels
      of activated NF-kappaB, and resistance to TRAIL could be reversed by LLnL and by
      the superrepressor form of IkappaBalpha. Therefore, these results suggest that
      activation of NF-kappaB by TRAIL plays an important role in resistance of
      melanoma cells to TRAIL-induced apoptosis and further suggest that inhibitors of
      NF-kappaB may be useful adjuncts in clinical use of TRAIL against melanoma.

PMID- 11313370
TI  - Papillomavirus-like particles induce acute activation of dendritic cells.
AB  - The role of viral structural proteins in the initiation of adaptive immune
      responses is poorly understood. To address this issue, we focused on the effect
      of noninfectious papillomavirus-like particles (VLPs) on dendritic cell (DC)
      activation. We found that murine bone marrow-derived dendritic cells (BMDCs)
      effectively bound and rapidly internalized bovine papillomavirus VLPS: Exposure
      to fully assembled VLPs of bovine papillomavirus, human papillomavirus (HPV)16 or
      HPV18, but not to predominately disordered HPV16 capsomers, induced acute
      phenotypic maturation of BMDCS: Structurally similar polyomavirus VLPs bound to
      the DC surface and were internalized, but failed to induce maturation. DCs that
      had incorporated HPV16 VLPs produced proinflammatory cytokines IL-6 and TNF
      alpha; however, the release of these cytokines was delayed relative to LPS
      activation. Production of IL-12p70 by VLP-exposed DCs required the addition of
      syngeneic T cells or rIFN-gamma. Finally, BMDCs pulsed with HPV16 VLPs induced
      Th1-dominated primary T cell responses in vitro. Our data provide evidence that
      DCs respond to intact papillomavirus capsids and that they play a central role in
      VLP-induced immunity. These results offer a mechanistic explanation for the
      striking ability of papillomavirus VLP-based vaccines to induce potent T and B
      cell responses even in the absence of adjuvant.

PMID- 11313371
TI  - Three-cell interactions in T cell-mediated suppression? A mathematical analysis
      of its quantitative implications.
AB  - Aiming to further our understanding of T cell-mediated suppression, we
      investigate the plausibility of the hypothesis that regulatory T cells suppress
      other T cells (target cells), while both cells are conjugated with one APC. We
      use a mathematical model to analyze the proliferation inhibition scored during in
      vitro suppression assays. This model is a radical simplification of cell culture
      reality, assuming that thymidine incorporation is proportional to the number of
      target cells that would instantaneously form conjugates with APCs that are free
      of regulatory cells. According to this model the inhibition index should be
      mainly determined by the number of regulatory cells per APC and should be
      insensitive to the number of target cells. We reanalyzed several published data
      sets, confirming this expectation. Furthermore, we demonstrate that the
      instantaneous inhibition index has an absolute limit as a function of the number
      of regulatory cells per APC. By calculating this limit we find that the model can
      explain the data under two non-mutually exclusive conditions. First, only
      approximately 15% of APCs used in the suppression assays form conjugates with T
      cells. Second, the growth of the regulatory cell population depends on the target
      cells, such that the number of regulatory cells per APC increases when they are
      cocultured with target cells and overcomes its limit. However, if neither of
      these testable conditions is fulfilled, then one could conclude that suppression
      in vitro does not require the formation of multicellular conjugates.

PMID- 11313372
TI  - Defined flanking spacers and enhanced proteolysis is essential for eradication of
      established tumors by an epitope string DNA vaccine.
AB  - Loss of immunogenic epitopes by tumors has urged the development of vaccines
      against multiple epitopes. Recombinant DNA technologies have opened the
      possibility to develop multiepitope vaccines in a relatively rapid and efficient
      way. We have constructed four naked DNA-based multiepitope vaccines, containing
      CTL, Th cell, and B cell epitopes of the human papillomavirus type 16. Here we
      show that gene gun-mediated vaccination with an epitope-based DNA vaccine
      protects 100% of the vaccinated mice against a lethal tumor challenge. The
      addition of spacers between the epitopes was crucial for the epitope-induced
      tumor protection, as the same DNA construct without spacers was significantly
      less effective and only protected 50% of the mice. When tested for therapeutic
      potential, only the epitope construct with defined spacers significantly reduced
      the size of established tumors, but failed to induce tumor regression. Only after
      targeting the vaccine-encoded protein to the protein degradation pathway by
      linking it to ubiquitin, the vaccine-induced T cell-mediated eradication of 100%
      of 7-day established tumors in mice. The finding that defined flanking sequences
      around epitopes and protein targeting dramatically increased the efficacy of
      epitope string DNA vaccines against established tumors will be of importance for
      the further development of multiepitope DNA vaccines toward clinical application.

PMID- 11313373
TI  - Engineering of macrophages to produce IFN-gamma in response to hypoxia.
AB  - Activation of murine macrophages (Mphi) requires the collaboration of signals
      derived from the immune system and the environment. In this study, we engineered
      a murine Mphi cell line to become activated in response to an environmental
      signal, hypoxia, as the sole stimulus. Hypoxia is a condition of low oxygen
      tension, occurring in several pathological tissues, which acts in synergy with
      IFN-gamma to induce full Mphi activation. We transfected the ANA-1 murine Mphi
      cell line with a construct containing the IFN-gamma gene controlled by a
      synthetic promoter inducible by hypoxia (HRE3x-Tk), and we characterized the
      cellular and molecular biology of the engineered Mphi under normoxia or hypoxia.
      Engineered Mphi in normoxia expressed basal levels of IFN-gamma mRNA and protein
      that were strongly augmented by shifting the cells to hypoxia. Furthermore, they
      responded to the synthesized IFN-gamma with induction of IFN-responsive factor-1
      and 2'-5'-oligoadenylate synthase expression. Under normoxic conditions, the
      engineered Mphi had a significant constitutive level of Ia Ags and Fc receptors.
      Hypoxia induced further augmentation of Ia and Fc expression. Finally, hypoxia
      induced inducible NO synthase expression, and subsequent reoxygenation led to the
      production of NO. In conclusion, the engineered Mphi, which produce IFN-gamma in
      an inducible manner, express new biochemical and functional properties in
      response to low oxygen environment as the sole stimulus, thereby circumventing
      the need for costimulation by other immune system-derived signals.

PMID- 11313374
TI  - HIV-1 gp120 stimulates the production of beta-chemokines in human peripheral
      blood monocytes through a CD4-independent mechanism.
AB  - The present study was designed to evaluate the effect of the HIV-1 envelope
      glycoprotein gp120 on the expression of beta-chemokines in cultured
      monocytes/macrophages. Treatment of either freshly isolated 1-day-cultured
      monocytes or 7-day-cultured monocyte-derived macrophages (MDM) with recombinant
      gp120-IIIB resulted in a specific and dose-dependent enhancement of secretion of
      monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta, and
      RANTES as well as a clear-cut increase in transcript accumulation. The expression
      of these mRNA was increased, but not superinduced, in the presence of
      cycloheximide. beta-Chemokine secretion was also induced after exposure of
      monocyte cultures to gp120-JRFL and aldrithiol-2-inactivated R5 and X4 HIV-1
      strains, retaining conformational and functional integrity of envelope proteins.
      In contrast, no beta-chemokine secretion was triggered by X4 and R5 gp120 or
      aldrithiol-2-inactivated virus treatment of monocytoid cell lines that were fully
      responsive to LPS. The gp120-mediated effect was independent of its interaction
      with CD4, as preincubation with soluble CD4 did not abrogate beta-chemokine
      induction. Moreover, triggering of CD4 receptor by a specific Ab did not result
      in any beta-chemokine secretion. Interestingly, engagement of CCR5 and CXCR4
      receptors by specific Abs as well as treatment with CCR5 and CXCR4 ligands
      induced beta-chemokine secretion. On the whole, these results indicate that HIV-1
      stimulates monocytes/macrophages to produce beta-chemokines by a specific
      interaction of gp120 with HIV-1 coreceptors on the cell membrane. The expression
      of these related polypeptides may represent an important cellular response for
      regulating both the extent of viral infection and the recruitment of immune
      cells.

PMID- 11313375
TI  - Ceramide inhibits lipopolysaccharide-mediated nitric oxide synthase and
      cyclooxygenase-2 induction in macrophages: effects on protein kinases and
      transcription factors.
AB  - The goal of this study was to elucidate whether triggering the sphingomyelin
      pathway modulates LPS-initiated responses. For this purpose we investigated the
      effects of N-acetylsphingosine (C(2)-ceramide) on LPS-induced production of NO
      and PGE(2) in murine RAW 264.7 macrophages and explored the signaling pathways
      involved. We found that within a range of 10-50 microM, C(2)-ceramide inhibited
      LPS-elicited NO synthase and cyclooxygenase-2 induction accompanied by a
      reduction in NO and PGE(2) formation. By contrast, a structural analog of C(2)
      ceramide that does not elicit functional activity, C(2)-dihydroceramide, did not
      affect the LPS response. The nuclear translocation and DNA binding study revealed
      that ceramide can inhibit LPS-induced NF-kappaB and AP-1 activation. The
      immunocomplex kinase assay indicated that IkappaB kinase activity stimulated by
      LPS was inhibited by ceramide, which concomitantly reduced the IkappaBalpha
      degradation caused by LPS within 1-6 h. In concert with the decreased cytosolic
      p65 protein level, LPS treatment resulted in rapid nuclear accumulation of NF
      kappaB subunit p65 and its association with the cAMP-responsive element binding
      protein. Ceramide coaddition inhibited all the LPS responses. In addition, LPS
      induced PKC and p38 mitogen-activated protein kinase activation were overcome by
      ceramide. In conclusion, we suggest that ceramide inhibition of LPS-mediated
      induction of inducible NO synthase and cyclooxygenase-2 is due to reduction of
      the activation of NF-kappaB and AP-1, which might result from ceramide's
      inhibition of LPS-stimulated IkappaB kinase, p38 mitogen-activated protein
      kinase, and protein kinase C.

PMID- 11313376
TI  - Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid
      cells.
AB  - The mechanism of tumor-associated T cell dysfunction remains an unresolved
      problem of tumor immunology. Development of T cell defects in tumor-bearing hosts
      are often associated with increased production of immature myeloid cells. In
      tumor-bearing mice, these immature myeloid cells are represented by a population
      of Gr-1(+) cells. In this study we investigated an effect of these cells on T
      cell function. Gr-1(+) cells were isolated from MethA sarcoma or C3 tumor-bearing
      mice using cell sorting. These Gr-1(+) cells expressed myeloid cell marker CD11b
      and MHC class I molecules, but they lacked expression of MHC class II molecules.
      Tumor-induced Gr-1(+) cells did not affect T cell responses to Con A and to a
      peptide presented by MHC class II. In sharp contrast, Gr-1(+) cells completely
      blocked T cell response to a peptide presented by MHC class I in vitro and in
      vivo. Block of the specific MHC class I molecules on the surface of Gr-1(+) cells
      completely abrogated the observed effects of these cells. Thus, immature myeloid
      cells specifically inhibited CD8-mediated Ag-specific T cell response, but not
      CD4-mediated T cell response. Differentiation of Gr-1(+) cells in the presence of
      growth factors and all-trans retinoic acid completely eliminated inhibitory
      potential of these cells. This may suggest a new approach to cancer treatment.

PMID- 11313377
TI  - The involvement of TNF-alpha-related apoptosis-inducing ligand in the enhanced
      cytotoxicity of IFN-beta-stimulated human dendritic cells to tumor cells.
AB  - TNF-alpha-related apoptosis-inducing ligand (TRAIL) is characterized by its
      preferential induction of apoptosis of tumor cells but not normal cells.
      Dendritic cells (DCs), besides their role as APCs, now have been demonstrated to
      exert cytotoxicity or cytostasis on some tumor cells. Here, we report that both
      human CD34(+) stem cell-derived DCs (CD34DCs) and human CD14(+) monocyte-derived
      DCs (MoDCs) express TRAIL and exhibit cytotoxicity to some types of tumor cells
      partially through TRAIL. Moderate expression of TRAIL appeared on CD34DCs from
      the 8th day of culture and was also seen on freshly isolated monocytes. The level
      of TRAIL expression remained constant until DC maturation. TRAIL expression on
      immature CD34DCs or MoDCs was greatly up-regulated after IFN-beta stimulation.
      Moreover, IFN-beta could strikingly enhance the ability of CD34DCs or MoDCs to
      kill TRAIL-sensitive tumor cells, but LPS did not have such an effect. The up
      regulation of TRAIL on IFN-beta-stimulated DCs partially contributed to the
      increased cytotoxicity of DCS: Pretreatment of TRAIL-sensitive tumor cells with
      caspase-3 inhibitor could significantly increase their resistance to the
      cytotoxicity of IFN-beta-stimulated DCS: In contrast, NF-kappaB inhibitor could
      significantly increase the sensitivity of tumor cells to the killing by
      nonstimulated or LPS-stimulated DCS: Our studies demonstrate that IFN-beta
      stimulated DCs are functionally cytotoxic. Thus, an innate mechanism of DC
      mediated antitumor immunity might exist in vivo in which DCs act as effectors to
      directly kill tumor cells partially via TRAIL. Subsequently, DCs act as APCs
      involved in the uptake, processing, and presentation of apoptotic tumor Ags to
      cross-prime CD8(+) CTL cells.

PMID- 11313378
TI  - Modulation of CD8+ T cell response to antigen by the levels of self MHC class I.
AB  - The response of H-Y-specific TCR-transgenic CD8(+) T cells to Ag is characterized
      by poor proliferation, cytolytic activity, and IFN-gamma secretion. IFN-gamma
      secretion, but not cytotoxic function, can be rescued by the B7.1 molecule,
      suggesting that costimulation can selectively enhance some, but not all, effector
      CD8(+) T cell responses. Although the H-Y epitope binds H-2D(b) relatively less
      well than some other epitopes, it can induce potent CTL responses in
      nontransgenic mice, suggesting that the observed poor responsiveness of
      transgenic CD8(+) T cells cannot be ascribed to the epitope itself. Previously
      reported reactivity of this TCR to H-2A(b) is also not the cause of the poor
      responsiveness of the H-Y-specific CD8(+) T cells, as H-Y-specific CD8(+) T cells
      obtained from genetic backgrounds lacking H-2A(b) also responded poorly. Rather,
      reducing the levels of H-2(b) class I molecules by breeding the mice to (C57BL/6
      x B10.D2)F(1) or TAP1(+/-) backgrounds partially restored cytotoxic activity and
      enhanced proliferative responses. These findings demonstrate that the self MHC
      class I gene dosage may regulate the extent of CD8(+) T cell responsiveness to
      Ag.

PMID- 11313379
TI  - META-controlled env-initiated transcripts encoding superantigens of murine Mtv29
      and Mtv7 and their possible role in B cell lymphomagenesis.
AB  - Spontaneous germinal center (GC)-derived B cell lymphomas of SJL mice (RCS)
      transcribe a 1.8-kb Mtv-29 mRNA under control of the META-env promoter. The
      encoded vSAg29 stimulates syngeneic Vbeta16(+) CD4(+) T cells, thereby acquiring
      T cell help necessary for RCS growth. Other strains of B cell lymphoma-prone mice
      include Mtv29(+) C57L and MA/MyJ, and the Mtv29(-) Mtv7(+)-recombinant inbred
      strain, SW x J-1. The lymphomas of these mice produce similar mouse mtv-vSAg
      encoding mRNA, as characterized by Northern blotting, PCR, and RNase protection.
      A 1.8-kb mRNA in C57L/J and MA/MyJ lymphomas hybridized with an Mtv29-specific
      oligonucleotide, whereas SW x J-1 lymphomas produced 1.8-kb transcripts
      hybridizing with an Mtv7-specific oligonucleotide. Similar META-env-initiated
      transcripts were absent from LPS-activated B cells from any strain examined but
      were detected in Peyer's patch RNA from SJL mice. Like typical SJL-derived RCS,
      all these lymphomas stimulated syngeneic CD4(+) T cells and Vbeta16(+) T
      hybridoma cells. Immunohistochemical staining of primary tumors showed the
      presence of peanut agglutinin binding (PNA(+)) highly mitotic lymphoblasts,
      suggesting their GC derivation. The findings indicate that this novel mRNA for
      Mtv29 is present in B cell lymphomas from several Mtv29(+) mouse strains.
      Additionally, this is the first description of the ability of Mtv7 to produce
      transcripts that are controlled and spliced identically to those of Mtv29 and
      that are expressed in SW x J-1, I-A(s+), lymphomas that also stimulate Vbeta16(+)
      T cells. Our results suggest an important role for mouse mtv-vSAgs and Vbeta16 T
      cell stimulation in the development of GC-derived murine B cell lymphomas.

PMID- 11313380
TI  - Antigen-specific primary activation of CD8+ T cells within the liver.
AB  - It is generally accepted that naive T cells recirculate via the blood and lymph,
      but do not enter nonlymphoid tissues without prior activation and
      differentiation. In this study, we demonstrate that the liver is an exception to
      this rule. Naive Des-TCR transgenic CD8(+) T cells specific for H-2K(b) were
      selectively retained in the liver within a few minutes of adoptive transfer into
      transgenic Met-K(b) mice expressing H-2K(b) in the liver. Activated CD8(+) cells
      were found in the liver, but not the blood, as soon as 2 h after transfer and
      underwent cell division and started to recirculate within 24 h of transfer. In
      contrast, CD8(+) cells activated in the lymph nodes remained sequestered at that
      site for 2 days before entering the blood. Our results therefore suggest that, in
      addition to its previously described role as a non Ag-specific activated T cell
      graveyard, the liver is involved in Ag-specific activation of naive recirculating
      CD8(+) T cells. This particular property of the liver, combined with the
      previously demonstrated ability of hepatocytes to induce tolerance by means of
      premature CD8(+) T cell death, may be a major mechanism contributing to the
      acceptance of liver allografts and the chronicity of viral hepatitis.

PMID- 11313381
TI  - The mechanism of a defective IFN-gamma response to bacterial toxins in an atopic
      dermatitis model, NC/Nga mice, and the therapeutic effect of IFN-gamma, IL-12, or
      IL-18 on dermatitis.
AB  - NC/Nga (NC) mice raised under conventional conditions (Conv. NC mice)
      spontaneously develop dermatitis similar to human atopic dermatitis, whereas NC
      mice raised under the specific pathogen-free conditions do not develop
      dermatitis. In the present study, we show that the representative Th1 cytokine,
      IFN-gamma levels in the sera of NC mice, injected with either staphylococcal
      enterotoxin B or endotoxin (LPS), to be severalfold lower than those of normal
      mice. The low IFN-gamma response to staphylococcal enterotoxin B was correlated
      to the lack of regular Vbeta8(+) T cells and Vbeta8(+) NK T cells, and the low
      IFN-gamma response to LPS was correlated to an impaired IL-18 production of
      macrophages. The CD3-stimulated IL-4 production from liver and spleen T cells
      from Conv. NC mice in vitro was greatly augmented. The serum IL-4 levels of
      untreated Conv. NC mice also were higher than those of normal mice and specific
      pathogen-free NC mice. Treatment of Conv. NC mice either with IFN-gamma, IL-12,
      or IL-18 twice a week from 4 wk of age substantially inhibited the elevation of
      the serum IgE levels, serum IL-4 levels, and dermatitis, and IL-12 or IL-18
      treatment also reduced the in vitro IL-4 production from CD3-stimulated liver T
      cells. The systemic deficiency in the Th1 response to bacterial stimulation thus
      leads to a Th2-dominant state and may induce an abnormal cellular immune response
      in the skin accompanied with an overproduction of IgE and a susceptibility to
      dermatitis in NC mice.

PMID- 11313382
TI  - Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic
      cell subsets.
AB  - Dendritic cells (DC) not only stimulate T cells effectively but are also
      producers of cytokines that have important immune regulatory functions. In this
      study we have extended information on the functional differences between DC
      subpopulations to include differences in the production of the major immune
      directing cytokines IL-12, IFN-alpha, and IFN-gamma. Splenic CD4(-)8(+) DC were
      identified as the major IL-12 producers in response to microbiological or T cell
      stimuli when compared with splenic CD4(-)8(-) or CD4(+)8(-) DC; however, all
      three subsets of DC showed similar IL-12 regulation and responded with increased
      IL-12 p70 production if IL-4 was present during stimulation. High level CD8
      expression also correlated with extent of IL-12 production for DC isolated from
      thymus and lymph nodes. By using gene knockout mice we ruled out any role for
      CD8alpha itself, or of priming by T cells, on the superior IL-12-producing
      capacity of the CD8(+) DC. Additionally, CD8(+) DC were identified as the major
      producers of IFN-alpha compared with the two CD8(-) DC subsets, a finding that
      suggests similarity to the human plasmacytoid DC lineage. In contrast, the CD4(
      )8(-) DC produced much more IFN-gamma than the CD4(-)8(+) or the CD4(+)8(-) DC
      under all conditions tested.

PMID- 11313383
TI  - Distinct autoreactive T cell responses to native and fragmented DNA topoisomerase
      I: influence of APC type and IL-2.
AB  - Systemic sclerosis (SSc) is an autoimmune connective tissue disease of unknown
      etiology in which T cell responses to various autoantigens, including DNA
      topoisomerase I (Topo I), have been implicated. We investigated whether dendritic
      cells, generally considered to be the most potent APCs for the initiation of
      immune responses, would present either of two forms of Topo I to T cells more
      efficiently than PBMC APCS: Using cells from healthy controls and SSc patients,
      several important observations were made. First, neither APC type was able to
      initiate T cell proliferative responses to full-length native Topo I unless
      exogenous IL-2 was added. This is in contrast to vigorous T cell proliferation in
      response to Topo I polypeptide fragments presented by either APC type. Second, T
      cell responses to the full-length form of Topo I presented by dendritic cells
      were considerably lower than responses to Ag presented by PBMC APCS: Finally, no
      secondary T cell responses were observed unless the same Ag/APC combination as
      that used in the primary stimulation was maintained. These data indicate that
      different peptides are generated based upon the form of the Topo I and the APC
      that processes it. Taken together, these results suggest that a very specific
      combination of antigenic form and APC may be involved in breaking tolerance to
      Topo I in the early stages of development of SSC:

PMID- 11313384
TI  - Fine tuning of TCR signaling by CD5.
AB  - Current data indicate that CD5 functions as an inhibitor of TCR signal
      transduction. Consistent with this role, thymocyte selection in TCR
      transgenic/CD5(-/-) mice is altered in a manner suggestive of enhanced TCR
      signaling. However, the impact of CD5 deletion on thymocyte selection varies
      depending on the transgenic TCR analyzed, ranging from a slight to a marked shift
      from positive toward negative selection. An explanation for the variable effect
      of CD5 on selection is suggested by the observation that CD5 surface expression
      is regulated by TCR signal intensity during development and CD5 surface levels on
      mature thymocytes and T cells parallel the avidity of the positively selecting
      TCR/MHC/ligand interaction. In this study, we generated mice that overexpress CD5
      during thymocyte development (CD5-tg), and then examined the effect of CD5
      overexpression or CD5 deletion (CD5(-/-)) on selection of thymocytes that express
      the same TCR transgenes. The results demonstrate that the effect on thymocyte
      selection of altering CD5 expression depends on the avidity of the selecting
      interaction and, consequently, the level of basal (endogenous) CD5 surface
      expression. Substitution of endogenous CD5 with a transgene encoding a truncated
      form of the protein failed to rescue the CD5(-/-) phenotype, demonstrating that
      the cytoplasmic domain of CD5 is required for its inhibitory function. Together,
      these results indicate that inducible regulation of CD5 surface expression during
      thymocyte selection functions to fine tune the TCR signaling response.

PMID- 11313385
TI  - Prime-boost immunization with DNA vaccine: mucosal route of administration
      changes the rules.
AB  - In this study we assessed prime-boost immunization strategies with a DNA vaccine
      (gB DNA) and attenuated recombinant vaccinia virus vector (rvacgB), both encoding
      the gB protein of HSV, for their effectiveness at inducing mucosal as well as
      systemic immunity to HSV. Confirming the reports of others, systemic priming with
      gB DNA and systemic boosting with rvacgB were the most effective means of
      inducing serum Ab and splenic T cell responses. Nevertheless, the systemic prime
      boost approach failed to induce detectable humoral or T cell responses at mucosal
      sites. However, such responses, at both proximal and distal locations, were
      induced if immunizations, especially the priming dose, were administered
      mucosally. Curiously, whereas optimal immunity with systemic priming and boosting
      occurred when gB DNA was used to prime and rvacgB was used as a boost, mucosal
      responses were optimal when animals were mucosally primed with rvacgB and boosted
      with gB DNA given mucosally. Furthermore, notable mucosal responses also occurred
      in animals mucosally primed with rvacgB and subsequently boosted systemically
      with gB DNA. Because the mucosal prime-boost immunization protocol also induced
      excellent systemic immune responses, the approach should be useful to vaccinate
      against agents for which both mucosal and systemic immunity are important for
      protection.

PMID- 11313386
TI  - CD150 association with either the SH2-containing inositol phosphatase or the SH2
      containing protein tyrosine phosphatase is regulated by the adaptor protein
      SH2D1A.
AB  - CD150 (SLAM/IPO-3) is a cell surface receptor that, like the B cell receptor,
      CD40, and CD95, can transmit positive or negative signals. CD150 can associate
      with the SH2-containing inositol phosphatase (SHIP), the SH2-containing protein
      tyrosine phosphatase (SHP-2), and the adaptor protein SH2 domain protein 1A
      (SH2D1A/DSHP/SAP, also called Duncan's disease SH2-protein (DSHP) or SLAM
      associated protein (SAP)). Mutations in SH2D1A are found in X-linked
      lymphoproliferative syndrome and non-Hodgkin's lymphomas. Here we report that
      SH2D1A is expressed in tonsillar B cells and in some B lymphoblastoid cell lines,
      where CD150 coprecipitates with SH2D1A and SHIP. However, in SH2D1A-negative B
      cell lines, including B cell lines from X-linked lymphoproliferative syndrome
      patients, CD150 associates only with SHP-2. SH2D1A protein levels are up
      regulated by CD40 cross-linking and down-regulated by B cell receptor ligation.
      Using GST-fusion proteins with single replacements of tyrosine at Y269F, Y281F,
      Y307F, or Y327F in the CD150 cytoplasmic tail, we found that the same
      phosphorylated Y281 and Y327 are essential for both SHP-2 and SHIP binding. The
      presence of SH2D1A facilitates binding of SHIP to CD150. Apparently, SH2D1A may
      function as a regulator of alternative interactions of CD150 with SHP-2 or SHIP
      via a novel TxYxxV/I motif (immunoreceptor tyrosine-based switch motif (ITSM)).
      Multiple sequence alignments revealed the presence of this TxYxxV/I motif not
      only in CD2 subfamily members but also in the cytoplasmic domains of the members
      of the SHP-2 substrate 1, sialic acid-binding Ig-like lectin, carcinoembryonic
      Ag, and leukocyte-inhibitory receptor families.

PMID- 11313387
TI  - Quantitation of lysozyme peptides bound to class II MHC molecules indicates very
      large differences in levels of presentation.
AB  - Knowing the abundance of peptides presented by MHC molecules is a crucial aspect
      for understanding T cell activation and tolerance. In this report we determined
      the relative abundance of four distinct peptide families after the processing of
      the model Ag hen egg-white lysozyme. The development of a sensitive
      immunochemical approach reported here made it possible to directly quantitate the
      abundance of these four epitopes presented by APCs, both in vitro and in vivo. We
      observed a wide range of presentation among these four different epitopes
      presented on the surface of APCs, with 250-fold differences or more between the
      most abundant epitope (48-63) and the least abundant epitopes. Importantly, we
      observe similar ratios of presentation from APCs in vitro as well as from APCs
      from the spleens and thymi of hen egg-white lysozyme transgenic mice. We discuss
      the relationship between the amount of peptide presented and their binding to I
      A(k) molecules, immunogenicity, and tolerogenicity.

PMID- 11313388
TI  - Prolonged exposure of T cells to TNF down-regulates TCR zeta and expression of
      the TCR/CD3 complex at the cell surface.
AB  - A role for TNF-alpha in the pathogenesis of chronic inflammatory disease is now
      firmly established. Paradoxically, TNF also has potent immunomodulatory effects
      on CD4(+) T lymphocytes, because Ag-specific proliferative and cytokine responses
      are suppressed following prolonged exposure to TNF. We explored whether TNF
      attenuated T cell activation by uncoupling proximal TCR signal transduction
      pathways using a mouse T cell hybridoma model. Chronic TNF exposure induced
      profound, but reversible, T cell hyporesponsiveness, with TNF-treated T cells
      requiring TCR engagement with higher peptide concentrations for longer periods of
      time for commitment to IL-2 production. Subsequent experiments revealed that
      chronic TNF exposure led to a reversible loss of TCRzeta chain expression, in
      part through a reduction in gene transcription. Down-regulation of TCRzeta
      expression impaired TCR/CD3 assembly and expression at the cell surface and
      uncoupled membrane-proximal tyrosine phosphorylation events, including
      phosphorylation of the TCRzeta chain itself, CD3epsilon, ZAP-70 protein tyrosine
      kinase, and linker for activation of T cells (LAT). Intracellular Ca(2+)
      mobilization was also suppressed in TNF-treated T cells. We propose that TNF may
      contribute to T cell hyporesponsiveness in chronic inflammatory and infectious
      diseases by mechanisms that include down-regulation of TCRzeta expression. We
      speculate that by uncoupling proximal TCR signals TNF could also interrupt
      mechanisms of peripheral tolerance that are dependent upon intact TCR signal
      transduction pathways.

PMID- 11313389
TI  - Essential requirement of antigen presentation by monocyte lineage cells for the
      activation of primary human gamma delta T cells by aminobisphosphonate antigen.
AB  - Human gammadelta T cells respond to nonpeptide Ags such as pyrophosphomonoesters
      and alkylamines in a gammadelta TCR-dependent manner in the absence of other
      APCS: Recently, aminobisphosphonates such as pamidronate have also been shown to
      activate human gammadelta T cells. In the present study, we indicate that
      activation of primary gammadelta T cells by pamidronate strictly depends on the
      presence of monocyte-lineage cells, unlike that by pyrophosphomonoesters. Thus,
      although pamidronate induced cell clustering, proliferation, and IFN-gamma
      production of gammadelta T cells in the culture of PBMC, it failed to induce any
      of these activities in the culture of purified primary gammadelta T cells. By
      adding back the purified monocytes, however, both cell clustering and IFN-gamma
      production of gammadelta T cells by pamidronate could be restored. The
      pamidronate-pulsed, but not untreated, myelomonocytic line, THP-1, was capable of
      activating the purified gammadelta T cells to produce IFN-gamma, which was
      associated with the down-regulation of gammadelta TCR. Furthermore, pamidronate
      pulsed THP-1 cells were significantly more susceptible to gammadelta T cell
      mediated cytotoxicity than untreated THP-1. Also, TCR-defective Jurkat T cells
      transfected with gammadelta TCR genes produced a significant level of IL-2 in
      response to the pamidronate-pulsed THP-1 cells. These results have suggested
      strongly that human gammadelta T cells are functionally activated via gammadelta
      TCR by aminobisphosphonate Ag presented on the surface of monocyte lineage cells
      rather than directly by its free form.

PMID- 11313390
TI  - Il-12 enhances CD8 T cell homeostatic expansion.
AB  - The size of the T lymphocyte pool is maintained by regulation of T cell
      production, proliferation, and survival. Under the pressure of a T lymphopenic
      environment, mature naive T cells begin to proliferate in the absence of Ag, a
      process called homeostatic expansion. Homeostatic expansion involves TCR
      recognition of self peptide/MHC ligands, but less is known about the soluble
      factors that regulate this process. Here we show that IL-12 dramatically enhanced
      the homeostatic proliferation of CD8 T cells. In contrast, IL-2 had no beneficial
      effect on homeostatic expansion and, in fact, inhibited T cell expansion induced
      by IL-12. Using gene-targeted mice, we showed that IL-12 acted directly on the T
      cells to enhance homeostatic expansion, but that IL-12 cannot override the
      requirement for TCR interaction with self peptide/MHC ligands in homeostatic
      expansion. These data indicate that inflammatory cytokines may modulate T cell
      homeostasis after lymphopenia and have implications for regulation of the T cell
      repertoire and autoimmunity.

PMID- 11313391
TI  - Lymphocyte lineages at mucosal effector sites: rat salivary glands.
AB  - Development of T cell lineages and the role of the thymus as a source of immature
      T cells in parotid (PG) and submandibular salivary glands (SMG) were studied in
      Fischer 344 rats using the Thy-1/CD45RC/RT6 expression model. In addition, the
      phenotypes of salivary gland lymphocytes were compared with other conventional
      and extrathymic populations. PG mononuclear cells consisted of T cells (38%), B
      cells (29%), and NK cells (4%). SMG had 19% T cells, 7% B cells, 37% NK cells,
      and an unusual population of CD3(-)/RT6(+) cells. In comparison with lymph node
      (LN), both PG and SMG were enriched in immature (Thy-1(+)) and activated (Thy-1(
      )/CD45RC(-)/RT6(-)) T cells. Unchanged percentages of Thy-1(+) T cells in PG and
      SMG following short-term adult thymectomy indicated that immature salivary gland
      T cells had an extrathymic source. In contrast, thymectomy eliminated LN recent
      thymic emigrants. SMG had T cells with characteristics of extrathymic
      populations, expressing TCRgammadelta(+) (28%), the CD8alphaalpha homodimer
      (11%), and NKR-P1A (66%). Many SMG T cells expressed integrin alpha(E)beta(7). PG
      T cells resembled those isolated from LN in respect to TCR and CD8 isoform usage,
      but were enriched in alpha(E)beta(7)(+) T cells and in NKT cells. Thus, salivary
      gland mononuclear cells are composed of a variety of subpopulations whose
      distributions differ between SMG and PG and are distinct from LN. These studies
      provide a basis for further investigation of regionalization in the mucosal
      immune network and are relevant to the design of vaccine regimens and
      intervention during pathological immune processes.

PMID- 11313392
TI  - IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory
      cells.
AB  - CD4(+) T regulatory type 1 (Tr1) cells suppress Ag-specific immune responses in
      vitro and in vivo. Although IL-10 is critical for the differentiation of Tr1
      cells, the effects of other cytokines on differentiation of naive T cells into
      Tr1 cells have not been investigated. Here we demonstrate that endogenous or
      exogenous IL-10 in combination with IFN-alpha, but not TGF-beta, induces naive
      CD4(+) T cells derived from cord blood to differentiate into Tr1 cells: IL
      10(+)IFN-gamma(+)IL-2(-/low)IL-4(-). Naive CD4(+) T cells derived from peripheral
      blood require both exogenous IL-10 and IFN-alpha for Tr1 cell differentiation.
      The proliferative responses of the Tr1-containing lymphocyte populations,
      following activation with anti-CD3 and anti-CD28 mAbs, were reduced. Similarly,
      cultures containing Tr1 cells displayed reduced responses to alloantigens via a
      mechanism that was partially mediated by IL-10 and TGF-beta. More importantly,
      Tr1-containing populations strongly suppressed responses of naive T cells to
      alloantigens. Collectively, these results show that IFN-alpha strongly enhances
      IL-10-induced differentiation of functional Tr1 cells, which represents a first
      major step in establishing specific culture conditions to generate T regulatory
      cells for biological and biochemical analysis, and for cellular therapy to induce
      peripheral tolerance in humans.

PMID- 11313393
TI  - Differential roles of Lck and Itk in T cell response to antigen recognition
      revealed by calcium imaging and electron microscopy.
AB  - Ag recognition triggered at the interface between a T cell and an APC is
      conditioned by cell-cell adhesion and cytoskeletal remodeling. The role played in
      these phenomena by Lck and Itk, two protein tyrosine kinases essential for T cell
      signaling, was examined. Early T cell responses (membrane ruffling, Ca(2+)
      response, APC-T cell adhesion) were monitored in T cells overexpressing kinase
      defective (KD) Lck and Itk mutants by combining fluorescence imaging and electron
      microscopy. Neither Lck nor Itk appears to be involved in the Ag-independent
      formation of a small and labile contact interface between T cells and APCS: By
      contrast, the Ag-induced Ca(2+) response in a cell population is similarly
      blunted in both KD transfectants. However, the underlying mechanisms are
      strikingly different for the two kinases. The major effect of Lck-KD is to reduce
      the probability of giving rise to quasi-normal Ca(2+) responses, whereas
      overexpression of Itk-KD results in a tuning down of all single-cell Ca(2+)
      responses. In addition, Lck, but not Itk, is required for the formation of a
      stable T/APC conjugate and for T cell polarization after Ag stimulation. Overall,
      our results lead to a clear distinction between Lck and ITK: Lck plays an
      ignition role, controlling all the downstream events tested here, whereas Itk
      amplifies the Ca(2+) response, but is dispensable for APC-induced adhesive and
      morphological responses.

PMID- 11313394
TI  - The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent
      protein kinase during neutrophil spreading.
AB  - The expression and phosphorylation state of the vasodilator-stimulated
      phosphoprotein (VASP), a membrane-associated focal adhesion protein, was
      investigated in human neutrophils. Adhesion and spreading of neutrophils induced
      the rapid phosphorylation of VASP. The phosphorylation of VASP was dependent on
      cell spreading, as VASP was expressed as a dephosphorylated protein in round
      adherent cells and was phosphorylated at the onset of changes in cell shape from
      round to spread cells. Immunofluorescence microscopy demonstrated that VASP was
      localized at the cell cortex in round cells and redistributed to focal adhesions
      at the ventral surface of the cell body during cell spreading. Dual labeling of
      spread cells indicated that VASP was colocalized with F-actin in filopodia and in
      focal adhesions, suggesting that the phosphorylation of VASP during cell
      spreading may be involved in focal adhesion complex organization and actin
      dynamics. VASP is a prominent substrate for both cGMP-dependent protein kinase
      (cGK) and cAMP-dependent protein kinase. Evidence suggested that cGK regulated
      neutrophil spreading, as both VASP phosphorylation and neutrophil spreading were
      inhibited by Rp-8-pCPT-cGMPS (cGK inhibitor), but not KT5720 (cAMP-dependent
      protein kinase inhibitor). In contrast, neutrophil spreading was accelerated when
      cGMP levels were elevated with 8-Br-cGMP, a direct activator of cGK. Furthermore,
      the same conditions that lead to VASP phosphorylation during neutrophil adherence
      and spreading induced significant elevations of cGMP in neutrophils. These
      results indicate that cGMP/cGK signal transduction is required for neutrophil
      spreading, and that VASP is a target for cGK regulation.

PMID- 11313395
TI  - Tumor progression despite efficient tumor antigen cross-presentation and
      effective "arming" of tumor antigen-specific CTL.
AB  - To determine whether APC function or "arming" of CTL for lytic function are the
      points at which Ags from a nonimmunogenic tumor fail to induce an effective
      immune response, we established a murine tumor model that expressed intracellular
      OVA and selected a clone (cOVA-9) that remained susceptible to lysis by specific
      CD8(+) T cells throughout tumor growth. Viable cOVA-9 tumor cells grew in normal
      mice at a rate similar to the parental tumor, and vaccination with irradiated
      cOVA-9 cells did not induce protection against itself or the parental line,
      confirming its nonimmunogenic status. In vivo evaluation during tumor growth
      demonstrated persisting tumor Ag cross-presentation accompanied by the generation
      of potent, specific CTL which were detectable when tumors were barely palpable.
      Despite the presence of highly active CTL in the tumor-draining lymph nodes,
      there was no apparent lysis of tumor-associated APC. These data show that tumor
      draining APC are not dysfunctional with regard to two crucial processes, in vivo
      tumor Ag cross-presentation and specific CTL arming, and that failure to prevent
      tumor growth is not in the induction phase, but in the effector phase and occurs
      within the tumor itself before the tumor matrix is established.

PMID- 11313396
TI  - CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane
      domains/rafts-mediated signaling system.
AB  - The glycosylphosphatidylinositol-anchored CD24 protein is a B cell
      differentiation Ag that is expressed on mature resting B cells but disappears
      upon Ag stimulation. We used Burkitt's lymphoma (BL) cells, which are thought to
      be related to germinal center B cells, to examine the biological effect of Ab
      mediated CD24 cross-linking on human B cells and observed 1) induction of
      apoptosis in BL cells mediated by cross-linking of CD24; and 2) synergism between
      the cross-linking of CD24 and that of the B cell receptor for Ag in the effect on
      apoptosis induction. We also observed activation of mitogen-activated protein
      kinases following CD24 cross-linking, suggesting that CD24 mediates the
      intracellular signaling that leads to apoptosis in BL cells. Although CD24 has no
      cytoplasmic portion to transduce signals intracellularly, analysis of
      biochemically separated glycolipid-enriched membrane (GEM) fractions indicated
      enhanced association of CD24 and Lyn protein tyrosine kinase in GEM as well as
      increased Lyn kinase activity after CD24 cross-linking, suggesting that CD24
      mediates intracellular signaling via a GEM-dependent mechanism. Specific
      microscopic cocapping of CD24 and Lyn, but not of other kinases, following CD24
      cross-linking supported this idea. We further observed that apoptosis induction
      by cross-linking is a common feature shared by GEM-associated molecules expressed
      on BL cells, including GPI-anchored proteins and glycosphingolipids. CD24
      mediated apoptosis in BL cells may provide a model for the cell death mechanism
      initiated by GEM-associated molecules, which is closely related to B cell
      receptor for Ag-mediated apoptosis.

PMID- 11313397
TI  - Stimulatory effects of B7-related protein-1 on cellular and humoral immune
      responses in mice.
AB  - Inducible costimulator (ICOS) and B7-related protein-1 (B7RP-1) constitute a
      receptor-ligand pair involved in T cell costimulation. In this study, the
      stimulatory effects of B7RP-1 on cellular and humoral immune responses were
      investigated giving mice a construct with the extracellular domain of murine B7RP
      1 fused with human IgG1 Fc (B7RP-1-Fc). B7RP-1-Fc stimulated contact
      hypersensitivity (CH) given near either the time of sensitization or challenge
      with oxazolone. When given near challenge time, B7RP-1-Fc stimulated CH more than
      a construct containing the extracellular domain of murine B7.2 and Fc (B7.2-Fc).
      B7RP-1-Fc increased the number of cells in lymph nodes draining the skin
      sensitized with oxazolone, especially activated T cells. B7RP-1-Fc also increased
      the ability of the cells in these lymph nodes to induce CH when transfused into
      naive mice. B7RP-1-Fc stimulated the production of anti-keyhole limpet hemocyanin
      (KLH) Ab, increasing anti-KLH IgG, IgG2a, and IgE, whereas B7.2-Fc did not affect
      this production. B7RP-1-Fc also increased the number of cells in lymph nodes
      draining the skin immunized with KLH and their production of IFN-gamma, IL-4, and
      IL-10 in response to KLH. Finally, B7RP-1-Fc increased the presence of
      eosinophils in the bronchoalveolar lavage and lungs of mice sensitized and
      challenged with OVA so to mount an asthmatic reaction. B7RP-1-Fc stimulates both
      cellular and humoral immune responses in vivo by increasing number and function
      of T and B cells reacting to Ag exposure.

PMID- 11313398
TI  - Fc alpha receptor cross-linking causes translocation of phosphatidylinositol
      dependent protein kinase 1 and protein kinase B alpha to MHC class II peptide
      loading-like compartments.
AB  - A20 IIA1.6 B cells cotransfected with FcalphaR and wild-type gamma-chain (wt-ITAM
      (immunoreceptor tyrosine-based activation motif)) or FcalphaR and gamma-chain, in
      which the wt-ITAM was substituted with the FcgammaRIIA ITAM (IIA-ITAM), were used
      to investigate cell signaling events influencing presentation of FcalphaR
      targeted exogenous Ag in the context of MHC class II. wt-ITAM cells presented
      FcalphaR-targeted OVA more efficiently than IIA-ITAM transfectants to OVA
      specific T cell hybridomas. Phosphatidylinositol 3-kinase (PI 3-kinase)
      inhibition abrogated Ag presentation, suggesting that FcalphaR may trigger a PI 3
      kinase-dependent signal transduction pathway, and thus phosphatidylinositol
      dependent protein kinase (PDK1) and protein kinase B alpha (PKBalpha) activation.
      Cross-linking FcalphaR on wt-ITAM or IIA-ITAM cells triggered equivalent PI 3
      kinase-dependent activation of PKBalpha. Furthermore, FcalphaR cross-linking
      triggered recruitment of PDK1 and serine-phosphorylated PKBalpha to capped cell
      surface FcalphaR irrespective of the gamma-chain ITAM. Although FcalphaR
      endocytosis was accompanied by translocation of PDK1 and phospho-PKBalpha to
      FcalphaR-containing vesicles in both transfectants, this was decreased in IIA
      ITAM cells, and a significant proportion of PDK1 and PKBalpha remained at the
      plasma membrane. In wt-ITAM cells, PDK1 and serine-phosphorylated PKBalpha
      translocated to lysosomal-associated membrane glycoprotein 1- and cathepsin B
      containing vesicles, consistent with MHC class II peptide-loading compartments
      (MIIC) described by other groups. Our data indicate that translocation of signal
      transduction mediators to MIIC-like compartments accompanies efficient
      presentation of receptor-targeted Ag, and suggest a mechanism connecting
      signaling to the Ag-processing pathway.

PMID- 11313399
TI  - Neonatal exposure to antigen induces a defective CD40 ligand expression that
      undermines both IL-12 production by APC and IL-2 receptor up-regulation on
      splenic T cells and perpetuates IFN-gamma-dependent T cell anergy.
AB  - T cell deletion and/or inactivation were considered the leading mechanisms for
      neonatal tolerance. However, recent investigations have indicated that immunity
      develops at the neonatal stage but evolves to guide later T cell responses to
      display defective and/or biased effector functions. Although neonatal-induced T
      cell modulation provides a useful approach to suppress autoimmunity, the
      mechanism underlying the biased function of the T cells remains unclear. In prior
      studies, we found that exposure of newborn mice to Ig-PLP1, a chimera expressing
      the encephalitogenic proteolipid protein (PLP) sequence 139-151, induced deviated
      Th2 lymph node cells producing IL-4 instead of IL-2 and anergic splenic T cells
      that failed to proliferate or produce IFN-gamma yet secreted significant amounts
      of IL-2. However, if assisted with IFN-gamma or IL-12, these anergic splenic T
      cells regained full responsiveness. The consequence of such biased/defective T
      cells responses was protection of the mice against experimental allergic
      encephalomyelitis. In this study, investigations were performed to delineate the
      mechanism underlying the novel form of IFN-gamma-dependent splenic anergy. Our
      findings indicate that CD40 ligand expression on these splenic T cells is
      defective, leading to noneffective cooperation between T lymphocytes and APCs and
      a lack of IL-12 production. More striking, this cellular system revealed a
      requirement for IL-2R expression for CD40 ligand-initiated, IL-12-driven
      progression of T cells into IFN-gamma production.

PMID- 11313400
TI  - Antigen recognition and immunomodulation by gamma delta T cells in bovine
      tuberculosis.
AB  - This report describes the in vitro proliferative responses of peripheral blood
      gammadelta T cells to defined mycobacterial protein Ags and the immunomodulatory
      effect of gammadelta T cells in cattle infected with Mycobacterium bovis.
      gammadelta T cell responses were specific to M. bovis infection because they were
      detected in cattle either experimentally or naturally infected with M. bovis, but
      were not present in uninfected controls. Proliferating gammadelta T cell cultures
      produced enhanced levels of IFN-gamma and TGF-beta, but not IL-2 in response to
      the more immunodominant mycobacterial AGS: Depletion of gammadelta T cells from
      PBMC resulted in an increased Ag-specific proliferation in half the animals
      tested, indicating a suppressive effect of gammadelta T cells upon other
      (alphabeta) T cell responses. Because gammadelta T cells constitute a major T
      cell population in the peripheral blood of cattle, the activities of gammadelta T
      cells described in this report could make a significant contribution to the
      immune response in bovine tuberculosis.

PMID- 11313401
TI  - Sanglifehrin A, a novel cyclophilin-binding immunosuppressant, inhibits IL-2
      dependent T cell proliferation at the G1 phase of the cell cycle.
AB  - Sanglifehrin A (SFA) is a novel immunosuppressive natural product that binds to
      cyclophilin but is structurally distinct from cyclosporin A (CsA). We have
      investigated the cellular and molecular mechanisms of the action of SFA in T
      lymphocytes. We show that SFA inhibits T cell proliferation induced by IL-2 with
      an IC(50) of 200 nM. Distinct from CsA, which also binds to cyclophilin, SFA does
      not affect calcium-dependent IL-2 production, although SFA enhanced IL-2 gene
      transcription in the same cells. SFA blocks T cell proliferation induced by IL-2
      in G(1) with no appreciable effect on IL-2 receptor expression in a manner
      similar to that of the immunosuppressant rapamycin. Unlike rapamycin, however,
      SFA has no effect on the phosphorylation or enzymatic activity of p70(s6k)
      kinase, distinguishing SFA from rapamycin in their mode of action. SFA inhibits
      hyperphosphorylation of Rb and the activity of cyclin E-cyclin-dependent kinase 2
      on IL-2 signaling. These results suggest that SFA has a novel mode of action in
      comparison with CsA, FK506, and rapamycin, and that its use as a molecular probe
      may lead to the discovery of a novel target involved in T cell activation.

PMID- 11313402
TI  - Il-12 antagonism enhances apoptotic death of T cells within hepatic allografts
      from Flt3 ligand-treated donors and promotes graft acceptance.
AB  - Mouse livers are accepted across MHC barriers and induce donor-specific tolerance
      without immunosuppressive therapy. By contrast, livers from donors treated with
      Flt3 ligand, which dramatically increases hepatic interstitial dendritic cells,
      are rejected acutely (median survival time 5 days). This switch from tolerance to
      rejection is associated with a marked reduction in apoptotic activity of graft
      infiltrating cells. We hypothesized that IL-12 production by enhanced numbers of
      donor APC might inhibit apoptosis, promote expansion of Th1 cells, and play a key
      role in liver rejection. Therefore, C3H (H2(k)) recipients of liver grafts from
      Flt3 ligand-treated B10 donors were given neutralizing anti-IL-12 mAb (200 or 500
      microg) on days 0 and 2 after transplant. Graft survival was markedly prolonged
      at the higher mAb dose, with 50% of grafts surviving >100 days. This effect was
      associated with reductions in IFN-gamma gene transcripts within the graft
      infiltrating cell population and with reductions in circulating IFN-gamma and IL
      10 levels, donor-specific CTL and NK cell activities, and circulating
      alloantibody levels. At the same time, there were marked increases in apoptotic
      (TUNEL(+)) CD4(+) and especially CD8(+) cells, both within the grafts and in
      spleens of anti-IL-12 mAb-treated mice. In vitro, exogenous IL-12 inhibited
      apoptotic death induced in naive allogeneic T cells by liver nonparenchymal
      cells. These findings suggest that suppression of rejection by IL-12 antagonism,
      linked to restoration of apoptotic activity within the peripheral alloreactive T
      cell population, is important for liver allograft survival and tolerance
      induction.

PMID- 11313403
TI  - Epitope mapping of antibodies to the C-terminal region of the integrin beta 2
      subunit reveals regions that become exposed upon receptor activation.
AB  - The cysteine-rich repeats in the stalk region of integrin beta subunits appear to
      convey signals impinging on the cytoplasmic domains to the ligand-binding
      headpiece of integrins. We have examined the functional properties of mAbs to the
      stalk region and mapped their epitopes, providing a structure-function map. Among
      a panel of 14 mAbs to the beta(2) subunit, one, KIM127, preferentially bound to
      alpha(L)beta(2) that was activated by mutations in the cytoplasmic domains, and
      by Mn(2+). KIM127 also bound preferentially to the free beta(2) subunit compared
      with resting alpha(L)beta(2). Activating beta(2) mutations also greatly enhanced
      binding of KIM127 to integrins alpha(M)beta(2) and alpha(X)beta(2). Thus, the
      KIM127 epitope is shielded by the alpha subunit, and becomes reexposed upon
      receptor activation. Three other mAbs, CBR LFA-1/2, MEM48, and KIM185, activated
      alpha(L)beta(2) and bound equally well to resting and activated alpha(L)beta(2),
      differentially recognized resting alpha(M)beta(2) and alpha(X)beta(2), and bound
      fully to activated alpha(M)beta(2) and alpha(X)beta(2). The KIM127 epitope
      localizes within cysteine-rich repeat 2, to residues 504, 506, and 508. By
      contrast, the two activating mAbs CBR LFA-1/2 and MEM48 bind to overlapping
      epitopes involving residues 534, 536, 541, 543, and 546 in cysteine-rich repeat
      3, and the activating mAb KIM185 maps near the end of cysteine-rich repeat 4. The
      nonactivating mAbs, 6.7 and CBR LFA-1/7, map more N-terminal, to subregions 344
      432 and 432-487, respectively. We thus define five different beta(2) stalk
      subregions, mAb binding to which correlates with effect on activation, and define
      regions in an interface that becomes exposed upon integrin activation.

PMID- 11313404
TI  - Mice triallelic for the Ig heavy chain locus: implications for VHDJH
      recombination.
AB  - V(H)DJ(H) recombination has been extensively studied in mice carrying an Ig heavy
      chain rearranged transgene. In most models, inhibition of endogenous Ig
      rearrangement occurs, consistently with the feedback model of IgH recombination.
      Nonetheless, an incomplete IgH allelic exclusion is a recurrent observation in
      these animals. Furthermore, transgene expression in ontogeny is likely to start
      before somatic recombination, thus limiting the use of Ig-transgenic mice to
      access the dynamics of V(H)DJ(H) recombination. As an alternative approach, we
      challenged the regulation of somatic recombination with the introduction of an
      extra IgH locus in germline configuration. This was achieved by reconstitution of
      RAG2(-/-) mice with fetal liver cells trisomic for chromosome 12 (Ts12). We found
      that all three alleles can recombine and that the ratio of Ig allotype-expressing
      B cells follows the allotypic ratio in trisomic cells. Although these cells are
      able to rearrange the three alleles, the levels of Ig phenotypic allelic
      exclusion are not altered when compared with euploid cells. Likewise, we find
      that most VDJ rearrangements of the silenced allele are unable to encode a
      functional mu-chain, indicating that the majority of these cells are also
      genetically excluded. These results provide additional support for the feedback
      model of allelic exclusion.

PMID- 11313405
TI  - Isoforms of Jun kinase are differentially expressed and activated in human
      monocyte/macrophage (THP-1) cells.
AB  - Ten isoforms of c-jun N-terminal kinase (JNK) have been described that arise by
      differential mRNA splicing of three genes. In that the relative expression and
      function of these different JNK proteins in human monocytic cells is not known,
      we have examined the JNK isoforms in THP-1 monocyte/macrophage cells.
      Differentiation of THP-1 cells by exposure to 10(-8) M PMA for 42-48 h enhances
      cellular responses to LPS, including enhanced activation of total JNK activity
      and increased phosphorylation of p54 JNK as well as p46 JNK. Examination of JNK
      proteins on Western blots reveals a predominance of p46 JNK1 and p54 JNK2
      proteins. Clearing of lysates by immunoprecipitation of JNK1(99% effective)
      removes 46% of the JNK enzymatic activity (p < 0.01), whereas clearing of JNK1
      plus JNK2 (70% effective) depletes the sample of 72% of the JNK activity (p <
      0.01). Further analysis, undertaken with real-time RT-PCR, revealed that 98% of
      the JNK messages code for three isoforms: JNK1beta1, JNK2alpha1, and JNK2alpha2.
      The p54 JNK that is phosphorylated in LPS-stimulated, PMA-differentiated THP-1
      cells is most likely JNK2alpha2 because 97% of the p54 JNK-encoding messages code
      for JNK2alpha2. By analogous reasoning, the p46 JNKs that are not heavily
      phosphorylated, but account for approximately half of the N-terminal c-jun kinase
      enzymatic activity, are most likely either JNK1beta1 or JNK2alpha1 because they
      account for 98% of the messages that can code for 46kDa JNKS:

PMID- 11313406
TI  - ZAP-70 and SLP-76 regulate protein kinase C-theta and NF-kappa B activation in
      response to engagement of CD3 and CD28.
AB  - The transcription factor NF-kappaB is a critical regulator of T cell function
      that becomes strongly activated in response to coengagement of TCR and CD28.
      Although events immediately proximal to NF-kappaB activation are well understood,
      uncertainty remains over which upstream signaling pathways engaged by TCR and
      CD28 lead to NF-kappaB activation. By using Jurkat T cell lines that are
      deficient or replete for either the protein tyrosine kinase ZAP-70 or the
      cytosolic adapter molecule SLP-76, the role of these proteins in modulating NF
      kappaB activation was examined. NF-kappaB was not activated in response to
      coengagement of TCR and CD28 in either the ZAP-70- or SLP-76-negative cells,
      whereas stimuli that bypass these receptors (PMA plus A23187, or TNF-alpha)
      activated NF-kappaB normally. Protein kinase C (PKC) theta activation, which is
      required for NF-kappaB activation, also was defective in these cells.
      Reexpression of ZAP-70 restored PKCtheta and NF-kappaB activation in response to
      TCR and CD28 coengagement. p95(vav) (Vav)-1 tyrosine phosphorylation was largely
      unperturbed in the ZAP-70-negative cells; however, receptor-stimulated SLP-76/Vav
      1 coassociation was greatly reduced. Wild-type SLP-76 fully restored PKCtheta and
      NF-kappaB activation in the SLP-76-negative cells, whereas 3YF-SLP-76, which
      lacks the sites of tyrosine phosphorylation required for Vav-1 binding, only
      partially rescued signaling. These data illustrate the importance of the ZAP
      70/SLP-76 signaling pathway in CD3/CD28-stimulated activation of PKC theta and NF
      kappaB, and suggest that Vav-1 association with SLP-76 may be important in this
      pathway.

PMID- 11313407
TI  - Protein kinase C-theta participates in the activation of cyclic AMP-responsive
      element-binding protein and its subsequent binding to the -180 site of the IL-2
      promoter in normal human T lymphocytes.
AB  - IL-2 gene expression is regulated by the cooperative binding of discrete
      transcription factors to the IL-2 promoter/enhancer and is predominantly
      controlled at the transcriptional level. In this study, we show that in normal T
      cells, the -180 site (-164/-189) of the IL-2 promoter/enhancer is a p-cAMP
      responsive element-binding protein (p-CREB) binding site. Following activation of
      the T cells through various membrane-initiated and membrane-independent pathways,
      protein kinase C (PKC)-theta phosphorylates CREB, which subsequently binds to the
      -180 site and associates with the transcriptional coactivator p300. Rottlerin, a
      specific PKC-theta inhibitor, diminished p-CREB protein levels when normal T
      cells were treated with it. Rottlerin also prevented the formation of p-CREB/p300
      complexes and the DNA-CREB protein binding. Cotransfection of fresh normal T
      cells with luciferase reporter construct driven by two tandem -180 sites and a
      PKC-theta construct caused a significant increase in the transcription of the
      reporter gene, indicating that this site is functional and regulated by PKC
      theta. Cotransfection of T cells with a luciferase construct driven by the 
      575/+57 region of the IL-2 promoter/enhancer and a PKC-theta construct caused a
      similar increase in the reporter gene transcription, which was significantly
      limited when two bases within the -180 site were mutated. These findings show
      that CREB plays a major role in the transcriptional regulation of IL-2 and that a
      major pathway for the activation of CREB and its subsequent binding to the IL-2
      promoter/enhancer in normal T cells is mediated by PKC-theta.

PMID- 11313408
TI  - Cloning, expression, and function of BLAME, a novel member of the CD2 family.
AB  - The CD2 family is a growing family of Ig domain-containing cell surface proteins
      involved in lymphocyte activation. Here we describe the cloning and expression
      analysis of a novel member of this family, B lymphocyte activator macrophage
      expressed (BLAME). BLAME shares the structural features of the CD2 family
      containing an IgV and IgC2 domain and clusters with the other family members on
      chromosome 1q21. Quantitative PCR and Northern blot analysis show BLAME to be
      expressed in lymphoid tissue and, more specifically, in some populations of
      professional APCs, activated monocytes, and DCS: Retroviral forced expression of
      BLAME in hematopoietic cells of transplanted mice showed an increase in B1 cells
      in the peripheral blood, spleen, lymph nodes, and, most strikingly, in the
      peritoneal cavity. These cells do not express CD5 and are CD23(low)Mac1(low),
      characteristics of the B1b subset. BLAME may therefore play a role in B lineage
      commitment and/or modulation of signal through the B cell receptor.

PMID- 11313409
TI  - Uncoordinated HLA-D gene expression in a RFXANK-defective patient with MHC class
      II deficiency.
AB  - We describe the analysis of a patient, JER, presenting classical immunological
      features of MHC class II deficiency. Unexpectedly, some HLA transcripts (HLA-DRA,
      HLA-DQA, and HLA-DMA) were found to be expressed in the JER cell line at nearly
      wild-type levels, while HLA-DPA and the HLA-D beta-chain transcripts were not
      detected. Gene reporter experiments confirmed the differential transcriptional
      activities driven by the HLA-D promoters in the JER cells. A defect in RFXANK was
      first suggested by genetic complementation analyses, then assessed with the
      demonstration of a homozygous mutation affecting a splice donor site downstream
      exon 4 of RFXANK. Because the severe deletion of the resulting protein cannot
      account for the expression of certain HLA-D genes, minor alternative transcripts
      of the RFXANK gene were analyzed. We thereby showed the existence of a transcript
      lacking exon 4, encoding a 28-aa-deleted protein that retains a transcriptional
      activity. Altogether, we characterize a new type of mutation in the RFXANK gene
      in a MHC class II-defective patient leading to an uncoordinated expression of the
      HLA-D genes, and propose that this phenotype is ensured by severely limited
      amounts of an active, although truncated RFXANK protein.

PMID- 11313410
TI  - Endotoxin-induced maturation of MyD88-deficient dendritic cells.
AB  - LPS, a major component of the cell wall of Gram-negative bacteria, can induce a
      variety of biological responses including cytokine production from macrophages, B
      cell proliferation, and endotoxin shock. All of them were completely abolished in
      MyD88-deficient mice, indicating the essential role of MyD88 in LPS signaling.
      However, MyD88-deficient cells still show activation of NF-kappaB and mitogen
      activated protein kinase cascades, although the biological significance of this
      activation is not clear. In this study, we have examined the effects of LPS on
      dendritic cells (DCs) from wild-type and several mutant mice. LPS-induced
      cytokine production from DCs was dependent on MyD88. However, LPS could induce
      functional maturation of MyD88-deficient DCs, including up-regulation of
      costimulatory molecules and enhancement of APC activity. MyD88-deficient DCs
      could not mature in response to bacterial DNA, the ligand for Toll-like receptor
      (TLR)9, indicating that MyD88 is differentially required for TLR family
      signaling. MyD88-dependent and -independent pathways originate at the
      intracytoplasmic region of TLR4, because both cytokine induction and functional
      maturation were abolished in DCs from C3H/HeJ mice carrying the point mutation in
      the region. Finally, in vivo analysis revealed that MyD88-, but not TLR4-,
      deficient splenic CD11c(+) DCs could up-regulate their costimulatory molecule
      expression in response to LPS. Collectively, the present study provides the first
      evidence that the MyD88-independent pathway downstream of TLR4 can lead to
      functional DC maturation, which is critical for a link between innate and
      adaptive immunity.

PMID- 11313411
TI  - Human cytomegalovirus pp65- and immediate early 1 antigen-specific HLA class I
      restricted cytotoxic T cell responses induced by cross-presentation of viral
      antigens.
AB  - Dendritic cells (DCs) play a pivotal role in the development of anti-viral CD8(+)
      CTL responses. This is straightforward if they are directly infected with virus,
      but is less clear in response to viruses that cannot productively infect DCS:
      Human CMV (HCMV) shows strain-specific cell tropism: fibroblast (Fb)-adapted
      laboratory strains (AD169) and recent clinical isolates do not infect DCs,
      whereas endothelial cell-adapted strains (TB40/E) result in productive lytic DC
      infection. However, we show here that uninfected DCs induce CD8(+) T cell
      cytotoxicity and IFN-gamma production against HCMV pp65 and immediate early 1 Ags
      following in vitro coculture with HCMV-AD169-infected Fbs, regardless of the HLA
      type of these FBS: CD8(+) T cell stimulation was inhibited by pretreatment of DCs
      with cytochalasin B or brefeldin A, indicating a phagosome/endosome to cytosol
      pathway. HCMV-infected Fbs were not apoptotic as measured by annexin V binding,
      and induction of apoptosis of infected Fbs in vitro did not augment CTL induction
      by DCs, suggesting a mechanism other than apoptosis in the initiation of cross
      presentation. Furthermore, HCMV-infected Fbs provided a maturation signal for
      immature DCs during coculture, as evidenced by increased CD83 and HLA class II
      expression. Cross-presentation of HCMV Ags by host DCs enables these professional
      APCs to bypass some of the evasion mechanisms HCMV has developed to avoid T cell
      recognition. It may also serve to explain the presence of immediate early 1 Ag
      specific CTLs in the face of pp65-induced inhibition of Ag presentation at the
      level of the infected cell.

PMID- 11313412
TI  - Neonatal T cells in an adult lung environment are competent to resolve
      Pneumocystis carinii pneumonia.
AB  - Initiation of the pulmonary inflammatory response to Pneumocystis carinii is
      delayed by 3 wk in mice infected as neonates compared with adults. There was no
      difference in the proliferative response of draining lymph node T cells from mice
      infected as neonates compared with adults when stimulated in vitro with either
      Con A or anti-CD3 mAB: However, TNF-alpha and IFN-gamma mRNA expression in the
      lungs of P. carinii-infected neonates was significantly lower than in adults
      indicating a lack of appropriate activation signaling in the local environment.
      This may have been due to active suppression because TGF-beta mRNA expression was
      significantly elevated in neonatal lungs compared with adults. To determine
      whether T cells from 10-day-old mice would effect resolution of P. carinii if
      harbored in an adult lung environment, cells were adoptively transferred to SCID
      mice with established P. carinii infections. There was no difference in the
      kinetics of T cell migration into the lungs or of clearance of P. carinii
      organisms when SCID mice were reconstituted with splenocytes from young mice as
      compared with adult mice. Furthermore, splenocytes from young mice stimulated
      both TNF-alpha and IFN-gamma mRNA expression to levels that were similar to that
      in the lungs of SCID mice reconstituted with adult cells. These data indicate
      that neonatal lymphocytes are competent to resolve P. carinii infection when
      harbored in an adult lung environment, suggesting that the neonatal lung
      environment, and not the T cells, is ineffective at responding to P. carinii
      infection.

PMID- 11313414
TI  - A heritable defect in IL-12 signaling in B10.Q/J mice. II. Effect on acute
      resistance to Toxoplasma gondii and rescue by IL-18 treatment.
AB  - This study documents a defect in IL-12-dependent IFN-gamma responses in a
      substrain (B10.Q-H2-(q)/SgJ) of B10.Q mice that manifests as an acute
      susceptibility to infection by the intracellular protozoan pathogen, Toxoplasma
      gondii. Despite robust systemic production of IL-12, infected B10.Q/J animals
      fail to mount an early IFN-gamma response after parasite inoculation. Genetic
      experiments revealed that the host resistance and IFN-gamma production defects
      are determined by a single autosomal recessive locus distinct from the Stat4
      gene. Nonetheless, a delayed IL-12-mediated IFN-gamma response emerges in later
      stages of acute infection but is unable to prevent host mortality. IL-18
      administration restores, in an IL-12-dependent manner, the early IFN-gamma
      response and host resistance of B10.Q/J animals. These in vivo studies indicate
      that the partially impaired IL-12 responsiveness in B10.Q/J mice can result in
      defective host resistance and demonstrate a therapeutic function for IL-18 in
      reversing a genetically based immunodeficiency in IL-12-dependent IFN-gamma
      production.

PMID- 11313413
TI  - A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis.
AB  - B10.Q mice are normally susceptible to the induction of collagen-induced
      arthritis. We noted that one subline of B10.Q mice, B10.Q/J, was completely
      resistant to disease induction when immunized with collagen in CFA. B10.Q/J mice
      have a global defect in the generation of Th1 responses, and Ag-specific T cells
      derived from this strain failed to produce IFN-gamma. Because T cells from these
      mice could produce normal amounts of IFN-gamma when activated by IL-12/IL-18
      independent stimuli, the defect appeared to be a failure to respond to IL-12.
      This defect extended to NK cells, which also failed to produce IFN-gamma when
      stimulated by IL-12. The capacity of NK cells, but not activated T cells, to
      produce IFN-gamma in response to IL-12 could be partially restored by IL-18. The
      expression of the IL-12R beta1- and beta2-chains on T cells and NK cells from
      B10.Q/J mice was normal. However, activated T cells from B10.Q/J mice did not
      signal normally through the IL-12R and manifested a defect in their capacity to
      phosphorylate Stat4. This defect was partial in that it could be overcome by
      increasing both the concentration of IL-12 and the incubation times in the Stat4
      phosphorylation assays. Because Stat4 function is apparently intact in B10.Q/J
      mice, the defect in IL-12 signaling can be localized between the IL-12R complex
      and Stat4. This subtle abnormality in IL-12 responsiveness results in a profound
      defect in the generation of Th1 cells and the development of autoimmune disease.

PMID- 11313415
TI  - A role for CD44 in the production of IFN-gamma and immunopathology during
      infection with Toxoplasma gondii.
AB  - The interaction of activated CD44 with its ligand, low m.w. hyaluronan, is
      involved in inflammation, but no role has been identified for this interaction in
      the regulation of an immune response to infection. In these studies, infection of
      C57BL/6 mice with Toxoplasma gondii resulted in increased expression of CD44 on T
      cells, B cells, NK cells, and macrophages, and a small percentage of CD4(+) T
      cells express an activated form of CD44. Administration of anti-CD44 to infected
      mice prevented the development of a CD4(+) T cell-dependent, infection-induced
      inflammatory response in the small intestine characterized by the overproduction
      of IFN-gamma. The protective effect of anti-CD44 treatment was associated with
      reduced production of IFN-gamma, but not IL-12, in vivo and in vitro.
      Furthermore, the addition of low m.w. hyaluronan to cultures of splenocytes or
      purified CD4(+) T cells from infected mice resulted in the production of high
      levels of IFN-gamma, which was dependent on IL-12 and TCR stimulation. Together,
      these results identify a novel role for CD44 in the regulation of IFN-gamma
      production by CD4(+) T cells during infection and demonstrate a role for CD44 in
      the regulation of infection-induced immune pathology.

PMID- 11313416
TI  - Improving vaccine potency through intercellular spreading and enhanced MHC class
      I presentation of antigen.
AB  - The potency of naked DNA vaccines is limited by their inability to amplify and
      spread in vivo. VP22, a HSV-1 protein, has demonstrated the remarkable property
      of intercellular transport and may thus provide a unique approach for enhancing
      vaccine potency. Therefore, we created a novel fusion of VP22 with a model Ag,
      human papillomavirus type 16 E7, in a DNA vaccine that generated enhanced
      spreading and MHC class I presentation of AG: These properties led to a dramatic
      increase in the number of E7-specific CD8(+) T cell precursors in vaccinated mice
      (around 50-fold) and converted a less effective DNA vaccine into one with
      significant potency against E7-expressing tumors. In comparison, nonspreading
      VP22(1-267) mutants failed to enhance vaccine potency. Our data indicated that
      the potency of DNA vaccines may be dramatically improved through intercellular
      spreading and enhanced MHC class I presentation of Ag.

PMID- 11313417
TI  - Salmonella pathogenicity island 2-encoded type III secretion system mediates
      exclusion of NADPH oxidase assembly from the phagosomal membrane.
AB  - Salmonella typhimurium requires a type III secretion system encoded by
      pathogenicity island (SPI)-2 to survive and proliferate within macrophages. This
      survival implies that S. typhimurium avoids or withstands bactericidal events
      targeted to the microbe-containing vacuole, which include intraphagosomal
      production of reactive oxygen species (ROS), phagosomal acidification, and
      delivery of hydrolytic enzymes to the phagosome via fusion with lysosomes. Recent
      evidence suggests that S. typhimurium alters ROS production by murine macrophages
      in an SPI-2-dependent manner. To gain insights into the mechanism by which S.
      typhimurium inhibits intraphagosomal ROS production, we analyzed the subcellular
      distribution of NADPH oxidase components during infection of human monocyte
      derived macrophages by wild-type (WT) or several SPI-2 mutant strains of S.
      typhimurium. We found that the membrane component of the NADPH oxidase,
      flavocytochrome b(558), was actively excluded or rapidly removed from the
      phagosomal membrane of WT-infected monocyte-derived macrophages, thereby
      preventing assembly of the NADPH oxidase complex and intraphagosomal production
      of superoxide anion. In contrast, the NADPH oxidase assembled on and generated
      ROS in phagosomes containing SPI-2 mutant S. typhimurium. Subversion of NADPH
      oxidase assembly by S. typhimurium was accompanied by increased bacterial
      replication relative to that of SPI-2 mutant strains, suggesting that the ability
      of WT S. typhimurium to prevent NADPH oxidase assembly at the phagosomal membrane
      represents an important virulence factor influencing its intracellular survival.

PMID- 11313418
TI  - Expression of stromal-derived factor-1 is decreased by IL-1 and TNF and in dermal
      wound healing.
AB  - Stromal-derived factor-1 (SDF-1) is a CXC chemokine that is believed to be
      constitutively expressed by stromal cells of numerous tissues. In this report, we
      demonstrate that dermal fibroblasts and vessels of noninflamed tissues express
      SDF-1. Unexpectedly, we found that expression of SDF-1 is regulated by
      inflammation. Expression of SDF-1 by primary cultures of human gingival
      fibroblasts is potently inhibited by activated macrophages via secretion of IL
      1alpha and TNF-alpha. Levels of SDF-1 mRNA also decrease in acutely inflamed
      mouse dermal wounds. We propose that SDF-1 functions as a homeostatic regulator
      of tissue remodeling, whose expression stabilizes existing dermal architecture.

PMID- 11313420
TI  - Eosinophils are a major source of nitric oxide-derived oxidants in severe asthma:
      characterization of pathways available to eosinophils for generating reactive
      nitrogen species.
AB  - Eosinophil recruitment and enhanced production of NO are characteristic features
      of asthma. However, neither the ability of eosinophils to generate NO-derived
      oxidants nor their role in nitration of targets during asthma is established.
      Using gas chromatography-mass spectrometry we demonstrate a 10-fold increase in 3
      nitrotyrosine (NO(2)Y) content, a global marker of protein modification by
      reactive nitrogen species, in proteins recovered from bronchoalveolar lavage of
      severe asthmatic patients (480 +/- 198 micromol/mol tyrosine; n = 11) compared
      with nonasthmatic subjects (52.5 +/- 40.7 micromol/mol tyrosine; n = 12).
      Parallel gas chromatography-mass spectrometry analyses of bronchoalveolar lavage
      proteins for 3-bromotyrosine (BrY) and 3-chlorotyrosine (ClY), selective markers
      of eosinophil peroxidase (EPO)- and myeloperoxidase-catalyzed oxidation,
      respectively, demonstrated a dramatic preferential formation of BrY in asthmatic
      (1093 +/- 457 micromol BrY/mol tyrosine; 161 +/- 88 micromol ClY/mol tyrosine; n
      = 11 each) compared with nonasthmatic subjects (13 +/- 14.5 micromol BrY/mol
      tyrosine; 65 +/- 69 micromol ClY/mol tyrosine; n = 12 each). Bronchial tissue
      from individuals who died of asthma demonstrated the most intense anti-NO(2)Y
      immunostaining in epitopes that colocalized with eosinophils. Although
      eosinophils from normal subjects failed to generate detectable levels of NO, NO(2
      ), NO(3-), or NO(2)Y, tyrosine nitration was promoted by eosinophils activated
      either in the presence of physiological levels of NO(2-) or an exogenous NO
      source. At low, but not high (e.g., >2 microM/min), rates of NO flux, EPO
      inhibitors and catalase markedly attenuated aromatic nitration. These results
      identify eosinophils as a major source of oxidants during asthma. They also
      demonstrate that eosinophils use distinct mechanisms for generating NO-derived
      oxidants and identify EPO as an enzymatic source of nitrating intermediates in
      eosinophils.

PMID- 11313419
TI  - Combinatorial model of chemokine involvement in glomerular monocyte recruitment:
      role of CXC chemokine receptor 2 in infiltration during nephrotoxic nephritis.
AB  - A sequential model involving chemokines has been proposed for leukocyte
      extravasation into areas of inflammation; however, site-specific aspects remain
      to be elucidated. Hence, we studied the role of chemokines produced by mesangial
      (MC) or glomerular endothelial cells (GEC) and their receptors in glomerular
      recruitment of monocytes. Stimulation of MC with TNF-alpha up-regulated mRNA and
      protein of CC and CXC chemokines but not constitutive expression of the CX(3)C
      chemokine fractalkine. While growth-related activity (GRO)-alpha was immobilized
      to MC proteoglycans, monocyte chemotactic protein (MCP)-1 was secreted into the
      soluble phase. Firm adhesion and sequestration of monocytes on activated MC was
      supported by the GRO-alpha receptor CXCR2 and to a lesser extent by CX(3)CR,
      whereas the MCP-1 receptor CCR2 contributed to their transendothelial chemotaxis
      toward activated MC. In contrast, fractalkine mRNA and protein was induced by TNF
      alpha in transformed rat GEC, and both CXCR2 and CX(3)CR mediated monocyte arrest
      on GEC in shear flow. The relevance of these mechanisms was confirmed in a rat
      nephrotoxic nephritis model where acute glomerular macrophage recruitment was
      profoundly inhibited by blocking CXCR2 or CCR2. In conclusion, our results
      epitomize a combinatorial model in which chemokines play specialized roles in
      driving glomerular monocyte recruitment and emphasize an important role for CXCR2
      in macrophage infiltration during early phases of nephrotoxic nephritis.

PMID- 11313421
TI  - Rapid depletion of peripheral antigen-specific T cells in TCR-transgenic mice
      after oral administration of myelin basic protein.
AB  - In myelin basic protein (MBP)-specific TCR-transgenic (Tg) mice, peripheral T
      cells express the Valpha2.3/Vbeta8.2-Tg TCR, demonstrate vigorous proliferative
      responses to MBP in vitro, and can exhibit experimental autoimmune
      encephalomyelitis (EAE) within 5 days of pertussis toxin injection. We explored
      the effects of oral administration of MBP on the cellular trafficking of the MBP
      specific TCR-Tg cells and the ability of oral MBP to protect Tg mice from EAE. Tg
      mice were fed MBP, OVA or vehicle and sacrificed at various times after feeding.
      An immediate and dramatic decrease in Valpha2.3/Vbeta8.2(+)-Tg cells was observed
      in the periphery within 1 h after feeding. By 3 days after feeding, the
      percentage of Tg cells increased to near control levels, but decreased again by
      10 days. When MBP or vehicle-fed Tg mice were challenged for EAE at this point,
      disease was severe in the vehicle-fed mice and reduced in the MBP-fed mice over
      the 40-day observation period. In vitro studies revealed a biphasic pattern of
      MBP proliferative unresponsiveness and an induction of Th1 cytokines.
      Immunohistochemical staining showed that the number of Tg cells found in the
      intestinal lamina propria increased dramatically as the number of Tg cells in the
      periphery decreased. There was no apparent proliferation of Tg cells in the
      lamina propria, indicating that Tg cells trafficked there from the periphery.
      Taken together, these results suggest that T cell trafficking into the site of Ag
      deposition acts to protect the TCR-Tg mouse from EAE.

PMID- 11313422
TI  - Carcinogen-induced inflammation and immunosuppression are enhanced in xeroderma
      pigmentosum group A model mice associated with hyperproduction of prostaglandin
      E2.
AB  - Xeroderma pigmentosum group A (XPA) gene-deficient mice easily developed skin
      cancers by the application of topical chemical carcinogens as well as by UV
      irradiation. As certain chemical carcinogens have been shown to be
      immunosuppressive, we examined the inflammatory and immunosuppressive effects of
      dimethylbenz(a)anthracene (DMBA) on XPA mice. Compared with wild-type mice, XPA
      mice showed greater ear swelling and reduction of epidermal Langerhans cells
      after DMBA application. Topical application of DMBA impaired the induction of
      contact hypersensitivity, initiated either locally or at distant sites. These
      DMBA-induced local and systemic immunosuppressions were more greatly enhanced in
      XPA mice than in wild-type mice. DMBA application induced pronounced production
      of PGE(2), IL-10, and TNF-alpha in the skin of XPA mice. Treatment with
      indomethacin, a potent inhibitor of PG biosynthesis, inhibited DMBA-induced
      inflammation and local immunosuppression. In XPA mice, increased serum IL-10 was
      detected after DMBA treatment. Excess production of PGE(2), TNF-alpha, and IL-10
      after DMBA application may be involved in the enhanced local and systemic
      immunosuppression in DMBA-treated XPA mice. Susceptibility to DMBA-induced skin
      tumors in XPA mice may be due to easy impairment of the immune system by DMBA in
      addition to a defect in the repair of DMBA-DNA adduct. Enhanced immunosuppression
      by chemical carcinogens as well as the mutagenicity of these mutagens might be
      associated with the high incidence of internal malignancies seen in XP patients.
      Moreover, these results supported the hypothesis that persistent DNA damage is a
      trigger for the production of immunoregulatory cytokines.

PMID- 11313423
TI  - A murine IL-4 receptor antagonist that inhibits IL-4- and IL-13-induced responses
      prevents antigen-induced airway eosinophilia and airway hyperresponsiveness.
AB  - The closely related Th2 cytokines, IL-4 and IL-13, share many biological
      functions that are considered important in the development of allergic airway
      inflammation and airway hyperresponsiveness (AHR). The overlap of their functions
      results from the IL-4R alpha-chain forming an important functional signaling
      component of both the IL-4 and IL-13 receptors. Mutations in the C terminus
      region of the IL-4 protein produce IL-4 mutants that bind to the IL-4R alpha
      chain with high affinity, but do not induce cellular responses. A murine IL-4
      mutant (C118 deletion) protein (IL-4R antagonist) inhibited IL-4- and IL-13
      induced STAT6 phosphorylation as well as IL-4- and IL-13-induced IgE production
      in vitro. Administration of murine IL-4R antagonist during allergen (OVA)
      challenge inhibited the development of allergic airway eosinophilia and AHR in
      mice previously sensitized with OVA. The inhibitory effect on airway eosinophilia
      and AHR was associated with reduced levels of IL-4, IL-5, and IL-13 in the
      bronchoalveolar lavage fluid as well as reduced serum levels of OVA-IGE: These
      observations demonstrate the therapeutic potential of IL-4 mutant protein
      receptor antagonists that inhibit both IL-4 and IL-13 in the treatment of
      allergic asthma.

PMID- 11313424
TI  - Possible involvement of EBV-mediated alpha-fodrin cleavage for organ-specific
      autoantigen in Sjogren's syndrome.
AB  - A cleavage product of alpha-fodrin may be an important organ-specific autoantigen
      in the pathogenesis of Sjogren's syndrome (SS), but the mechanisms of alpha
      fodrin cleavage remain unclear. Since EBV has been implicated in the pathogenesis
      of SS, we determined whether EBV activation could induce the SS-specific 120-kDa
      autoantigen alpha-fodrin. ZEBRA mRNA expression, a marker for activation of the
      lytic cycle of EBV, was found in the salivary gland tissues from SS patients, but
      not in those from control individuals. ZEBRA-expressing lymphoid cells were also
      found in the SS glands in double-stained immunohistochemistry. Furthermore, a
      significant link between production of Abs against 120-kDa alpha-fodrin and
      reactivated EBV Ag was found in sera from patients with SS, but not in those from
      control individuals. EBV-activated lymphoid cells showed specific alpha-fodrin
      cleavage to the expected 120-kDa fragments in vitro. Pretreatment with caspase
      inhibitors inhibited cleavage of alpha-fodrin. Thus, an increase in apoptotic
      protease activities induced by EBV reactivation may be involved in the
      progression of alpha-fodrin proteolysis in the development of SS.

PMID- 11313425
TI  - SIN-1, a nitric oxide donor, ameliorates experimental allergic encephalomyelitis
      in Lewis rats in the incipient phase: the importance of the time window.
AB  - NO is involved in the regulation of immune responses. The role of NO in the
      pathogenesis of experimental allergic encephalomyelitis (EAE) is controversial.
      In this study, 3-morpholinosydnonimine (SIN-1), an NO donor, was administered to
      Lewis rats on days 5-7 postimmunization, i.e., during the incipient phase of EAE.
      SIN-1 reduced clinical signs of EAE compared with those in PBS-treated control
      rats and was accompanied by reduced ED1(+) macrophages and CD4(+) T cell
      infiltration within the CNS. Blood mononuclear cells (MNC) obtained on day 14
      postimmunization revealed that SIN-1 administration enhanced NO and IFN-gamma
      production by blood MNC and suppressed Ag- and mitogen-induced proliferative
      responses. MHC class II, B7-1 and B7-2 were down-regulated in SIN-1-treated EAE
      rats. Simultaneously, frequencies of apoptotic cells among blood MNC were
      increased. In vivo, SIN-1 is likely to behave as an NO donor. Administration of
      SIN-1 induced NO production, but did not affect superoxide and peroxynitrite
      formation. Enhanced NO production during the priming phase of EAE thus promotes
      apoptosis, down-regulates disease-promoting immune reactivities, and ameliorates
      clinical EAE, mainly through SIN-1-derived NO, without depending on NO synthase.

PMID- 11313426
TI  - Kinetics of TCR use in response to repeated epitope-specific immunization.
AB  - Selection of T cell-directed immunization strategies is based extensively on
      discordant information derived from preclinical models. We characterized the
      kinetics of T cell selection in response to repeated antigenic challenge. By
      enumerating with epitope/HLA tetrameric complexes (tHLA) vaccine-elicited T cell
      precursor frequencies (Tc-pf) in melanoma patients exposed to the modified gp100
      epitope gp100:209-217 (g209-2M) we observed in most patients that the Tc-pf
      increased with number of immunizations. One patient's kinetics were further
      characterized. Dissociation kinetics of g209-2M/tHLA suggested enrichment of T
      cell effector populations expressing TCR with progressively higher affinity.
      Furthermore, vaccine-elicited T cells maintained the ability to express IFN-gamma
      ex vivo and proliferate in vitro. Thus, repeated exposure to immunogenic peptides
      benefited immune competence. These results provide a rationale for immunization
      strategies.

PMID- 11313427
TI  - Cognate T cell help is sufficient to trigger anti-nuclear autoantibodies in naive
      mice.
AB  - The mechanisms involved in the initiation of anti-nuclear autoantibodies are
      unknown. In this study, we show that one factor allowing anti-nuclear
      autoantibodies to develop is the incomplete nature of immune tolerance to many of
      these proteins. Immune responses in mice toward the ubiquitous nuclear
      autoantigen La/SS-B are much weaker than responses to the xenoantigen, human La
      (hLa; 74% identical). However, in transgenic (Tg) mice expressing hLa, the Ab
      response to this neo-autoantigen was reduced to a level resembling the weak
      autoimmune response to mouse LA: Partial tolerance to endogenous La autoantigen
      was restricted to the T compartment because transfer of CD4(+) T cells specific
      for one or more hLa determinants into mice bearing the hLa transgene was
      sufficient to elicit production of anti-hLa autoantibodies. Notably, only hLa-
      specific T cells from non-Tg mice, and not T cells from hLa Tg mice, induced
      autoantibody production in hLa Tg mice. These findings confirm partial Th
      tolerance to endogenous La and indicate the existence in normal animals of
      autoreactive B cells continuously presenting La nuclear AG: Therefore, the B cell
      compartment is constitutively set to respond to particular nuclear autoantigens,
      implicating limiting Th responses as a critical checkpoint in the development of
      anti-nuclear autoantibodies in normal individuals.

PMID- 11313428
TI  - Anti-CD3 epsilon F(ab')2 prevents graft-versus-host disease by selectively
      depleting donor T cells activated by recipient alloantigens.
AB  - Transplantation tolerance is facilitated by activation-induced apoptosis of
      peripheral T cells triggered by specific AG: Abs specific for the nonpolymorphic
      CD3 component of the TCR complex bind to APCs through Fc-FcR interactions, mimic
      MHC-peptide, and activate polyclonal T cells. In contrast, F(ab')(2) of anti
      CD3epsilon Abs do not activate naive T cells but induce apoptosis of Ag
      activated, cycling T cells. Here, we report that treatment with anti-CD3epsilon
      F(ab')(2) can selectively induce apoptosis of donor T cells that recognize a
      recipient alloantigen, thereby preventing graft-vs-host disease initiated by a
      TCR-transgenic T cell population. The selective elimination of Ag-activated T
      cells by non-FcR-binding anti-CD3epsilon Abs could serve as an ideal strategy to
      prevent graft-vs-host disease and allograft rejection or to treat autoimmune
      disorders.

PMID- 11313429
TI  - Chloride channels go cell cycling.

PMID- 11313430
TI  - Osmotic swelling-induced ATP release: a new role for tyrosine and Rho-kinases?

PMID- 11313431
TI  - Functional roles of gamma2, gamma3 and gamma4, three new Ca2+ channel subunits,
      in P/Q-type Ca2+ channel expressed in Xenopus oocytes.
AB  - Stargazin or [gamma]2, the product of the gene mutated in the stargazer mouse, is
      a homologue of the [gamma]1 protein, an accessory subunit of the skeletal muscle
      L-type Ca2+ channel. [gamma]2 is selectively expressed in the brain, and
      considered to be a putative neuronal Ca2+ channel subunit based mainly on
      homology to [gamma]1. Two new members of the [gamma] family expressed in the
      brain have recently been identified: [gamma]3 and [gamma]4. We have co-expressed,
      in Xenopus oocytes, the human [gamma]2, [gamma]3 and [gamma]4 subunits with the
      P/Q-type (Ca(V)2.1) Ca2+ channel and different regulatory subunits ([alpha]2
      [delta]; [beta]1, [beta]2, [beta]3 or [beta]4). Subcellular distribution of the
      [gamma] subunits confirmed their membrane localization. Ba2+ currents, recorded
      using two-electrode voltage clamp, showed that the effects of the [gamma]
      subunits on the electrophysiological properties of the channel are, most of the
      time, minor. However, a fraction of the oocytes expressing [beta] subunits
      displayed an unusual slow-inactivating Ba2+ current. Expression of both [beta]
      and [gamma] subunits increased the appearance of the slow-inactivating current.
      Our data support a role for the [gamma] subunit as a brain Ca2+ channel
      modulatory subunit and suggest that [beta] and [gamma] subunits are involved in a
      switch between two regulatory modes of the P/Q-type channel inactivation.

PMID- 11313432
TI  - Oxytocin retrogradely inhibits evoked, but not miniature, EPSCs in the rat
      supraoptic nucleus: role of N- and P/Q-type calcium channels.
AB  - We previously reported that oxytocin (OXT), released from the dendrites of
      magnocellular neurons in the supraoptic nucleus (SON), acts retrogradely on
      presynaptic terminals to inhibit glutamatergic transmission. Here we test the
      hypothesis that oxytocin reduces calcium influx into the presynaptic terminal. We
      used nystatin perforated-patch recording in vitro to first identify the calcium
      channels involved in glutamatergic transmission in the SON. [omega]-Conotoxin
      GVIA ([omega]-CTx) and [omega]-Agatoxin TK ([omega]-Aga) both reduced evoked EPSC
      amplitude, while nicardipine and nickel had no effect. A combination of [omega]
      CTx and [omega]-Aga completely abolished the evoked EPSCs. This depressant effect
      was accompanied by an increase in the paired pulse ratio with no change in the
      kinetics of the evoked EPSCs, AMPA currents or postsynaptic cell properties.
      These results suggest that presynaptic N- and P/Q-type calcium channels mediate
      glutamate release in the SON while L-, T- and R-type channels make little or no
      contribution. Oxytocin-induced reduction of the evoked EPSC was substantially
      occluded in the presence of [omega]-CTx but only partially in the presence of
      [omega]-Aga. Amastatin, an endopeptidase inhibitor that increases the level of
      endogenous OXT, also reduced the evoked EPSC. This amastatin effect was also
      occluded by [omega]-CTx and [omega]-Aga. Miniature EPSCs, which are independent
      of extracellular calcium, were unaffected by either [omega]-CTx or by OXT, thus
      further substantiating an action of both compounds on calcium channels.
      Therefore, dendritically released oxytocin acts mainly via a mechanism involving
      the N-type channel, and to a lesser extent the P/Q-type channel, to decrease
      excitatory transmission.

PMID- 11313433
TI  - Nifedipine blocks Ca2+ store refilling through a pathway not involving L-type
      Ca2+ channels in rabbit arteriolar smooth muscle.
AB  - This study assessed the contribution of L-type Ca2+ channels and other Ca2+ entry
      pathways to Ca2+ store refilling in choroidal arteriolar smooth muscle. Voltage
      clamp recordings were made from enzymatically isolated choroidal microvascular
      smooth muscle cells and from cells within vessel fragments (containing < 10
      cells) using the whole-cell perforated patch-clamp technique. Cell Ca2+ was
      estimated by fura-2 microfluorimetry. After Ca2+ store depletion with caffeine
      (10 mM), refilling was slower in cells held at -20 mV compared to -80 mV
      (refilling half-time was 38 +/- 10 and 20 +/- 6 s, respectively). To attempt
      faster refilling via L-type Ca2+ channels, depolarising steps from -60 to -20 mV
      were applied during a 30 s refilling period following caffeine depletion. Each
      step activated L-type Ca2+ currents and [Ca2+]i transients, but failed to
      accelerate refilling. At -80 mV and in 20 mM TEA, prolonged caffeine exposure
      produced a transient Ca2+-activated Cl- current (I(Cl)(Ca)) followed by a smaller
      sustained current. The sustained current was resistant to anthracene-9-carboxylic
      acid (1 mM; an I(Cl)(Ca) blocker) and to BAPTA AM, but was abolished by 1 microM
      nifedipine. This nifedipine-sensitive current reversed at +29 +/- 2 mV, which
      shifted to +7 +/- 5 mV in Ca2+-free solution. Cyclopiazonic acid (20 microM; an
      inhibitor of sarcoplasmic reticulum Ca2+-ATPase) also activated the nifedipine
      sensitive sustained current. At -80 mV, a 5 s caffeine exposure emptied Ca2+
      stores and elicited a transient I(Cl)(Ca). After 80 s refilling, another caffeine
      challenge produced a similar inward current. Nifedipine (1 microM) during
      refilling reduced the caffeine-activated I(Cl)(Ca) by 38 +/- 5 %. The effect was
      concentration dependent (1-3000 nM, EC50 64 nM). In Ca2+-free solution, store
      refilling was similarly depressed (by 46 +/- 6 %). Endothelin-1 (10 nM) applied
      at -80 mV increased [Ca2+]i, which subsided to a sustained 198 +/- 28 nM above
      basal. Cell Ca2+ was then lowered by 1 microM nifedipine (to 135 +/- 22 nM),
      which reversed on washout. These results show that L-type Ca2+ channels fail to
      contribute to Ca2+ store refilling in choroidal arteriolar smooth muscle.
      Instead, they refill via a novel non-selective store-operated cation conductance
      that is blocked by nifedipine.

PMID- 11313434
TI  - The functional role of a bicuculline-sensitive Ca2+-activated K+ current in rat
      medial preoptic neurons.
AB  - A Ca2+-activated K+ current was identified in neurons from the rat medial
      preoptic nucleus. Its functional role for the resting potential and for impulse
      generation was characterised by using the reversible blocking agent bicuculline
      methiodide. Acutely dissociated neurons were studied by perforated-patch
      recordings. The effect of bicuculline methiodide was investigated under voltage
      clamp conditions to clearly identify the current affected. At membrane potentials
      > -50 mV, bicuculline methiodide rapidly (< 1 s) and reversibly blocked a steady
      outward current. Half-saturating concentration was 12 microM. The current
      amplitude increased with potential in the range -50 to 0 mV. The bicuculline
      sensitive current was identified as an apamin-sensitive, Ca2+-dependent K+
      current. It was neither affected by the GABAA receptor blocker picrotoxin (100
      microM) nor by a changed pipette Cl- concentration, but was affected by
      substitution of extracellular K+ for Na+. The current was dependent on
      extracellular Ca2+ and was sensitive to 1 microM apamin but not to 200 nM
      charybdotoxin. A role for the Ca2+-dependent K+ current in setting the resting
      potential and controlling spontaneous firing frequency was observed under current
      clamp conditions. Bicuculline methiodide (100 microM) induced a positive shift (5
      +/- 1 mV; n = 18) of resting potential in all neurons tested. In the majority of
      spontaneously firing neurons, the firing frequency was reversibly affected,
      either increased or decreased depending on the cell, by bicuculline methiodide.

PMID- 11313435
TI  - Repetitive nerve stimulation decreases the acetylcholine content of quanta at the
      frog neuromuscular junction.
AB  - We investigated how elevated quantal release produced by motor nerve stimulation
      affects the size of the quanta. The motor nerve was stimulated at 10 Hz in
      preparations in which excitation-contraction coupling was disrupted. Two hundred
      stimuli reduced the size of the time integrals of the miniature endplate currents
      ([integral]MEPCs), measured at the same junction immediately after stimulation,
      by 16 %. Three thousand stimuli reduced size by 23 %. When the solution contained
      10 microM neostigmine (NEO) 3000 stimuli reduced [integral]MEPCs by 60 %, because
      with acetylcholinesterase (AChE) inhibited, [integral]MEPC size is more sensitive
      to changes in acetylcholine (ACh) content. Similar decreases in miniature
      endplate potential size ([integral]MEPP) followed repetitive stimulation of
      contracting preparations. The depolarization produced by iontophoretic pulses of
      ACh was scarcely changed by 3000 nerve stimuli at 10 Hz, suggesting that the
      decreases in miniature sizes are largely due to less ACh released per quantum.
      Following 3000 stimuli at 10 Hz the sizes of the [integral]MEPCs increased back
      to pre-stimulus values with a half-time of 8-10 min. Recovery was blocked by (-)
      vesamicol (VES), by hemicholinium-3 (HC3) and by nicotinic cholinergic agonists -
      all of which inhibit ACh loading into synaptic vesicles. The number of quanta in
      the total store was estimated by releasing them with carbonyl cyanide m
      chlorophenylhydrazone (CCCP). CCCP releases fewer quanta after stimulation than
      from unstimulated controls. After resting for hours following stimulation, the
      releasable number increased, even when ACh loading inhibitors were present. We
      conclude that the inhibitors do not block a significant fraction of the ACh
      loading into reformed reserve vesicles and propose that ACh can be loaded in a
      series of steps.

PMID- 11313436
TI  - Overexpression of rat neuronal calcium sensor-1 in rodent NG108-15 cells enhances
      synapse formation and transmission.
AB  - The role of rat neuronal calcium sensor-1 (NCS-1), a Ca2+-binding protein, in
      synapse formation and transmitter release was examined in mouse neuroblastoma x
      rat glioma hybrid NG108-15 cells in culture. Wild-type NG108-15 cells expressed
      rodent NCS-1. Endogenous NCS-1 was partially co-localized with the synaptic
      protein SNAP-25 at the plasma membrane in both cell bodies and processes, but not
      with the Golgi marker [beta]-COP, an individual coat subunit of the coatomer
      complex present on Golgi-derived vesicles. In NG108-15 cells co-cultured with rat
      myotubes, partial co-localization of SNAP-25 and NCS-1 was observed at the plasma
      membrane of neurites and growth cones, some of which had synaptic contacts to
      muscle cells. Transient co-transfection of the rat NCS-1 cDNA and green
      fluorescent protein (GFP) resulted in NCS-1 overexpression in about 30 % of the
      cells as determined by fluorescence microscopy. The rate of functional synapse
      formation with co-cultured rat myotubes increased 2-fold as determined by the
      presence of miniature endplate potentials (MEPPs) in NCS-1-overexpressing NG108
      15 cells compared to non- and mock-transfected cells. The number of neurites per
      cell, branches per neurite and length of neurites was slightly less in cells that
      were either transiently transfected (GFP-NCS-1-fluorescence positive) or stably
      transformed with NCS-1 compared to GFP-NCS-1-negative, non-transfected or mock
      transfected NG108-15 cells. The number of action potentials that elicited
      endplate potentials increased in NG108-15 cells stably transformed with rat NCS
      1. The mean number of quanta per impulse (m) increased 5-fold. These results show
      that NCS-1 functions to facilitate synapse formation, probably because of the
      increased quantal content of evoked acetylcholine release.

PMID- 11313437
TI  - Blocking swelling-activated chloride current inhibits mouse liver cell
      proliferation.
AB  - A non-transformed mouse liver cell line (AML12) was used to show that blocking
      swelling-activated membrane Cl- current inhibits hepatocyte proliferation. Two
      morphologically distinguishable cell populations exhibited distinctly different
      responses to hypotonic stress. Hypotonic stress (from 280 to 221 mosmol kg(-1))
      to rounded, dividing cells activated an ATP-dependent, outwardly rectifying,
      whole-cell Cl- current, which took 10 min to reach maximum conductance. A similar
      anionic current was present spontaneously in 20 % of the dividing cells.
      Hypotonic stress to flattened, non-dividing cells activated no additional
      current. The Eisenman halide permeability sequence of swelling-activated anionic
      current in the dividing cells was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate.
      Addition of either 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), 5-nitro
      2-(3-phenylpropylamino) benzoic acid (NPPB), tamoxifen or mibefradil inhibited
      swelling-activated anionic current. Hyperosmolarity by added sucrose inhibited
      the spontaneous anionic current in dividing cells. Added Cl- channel blockers
      NPPB (IC50 = 40 microM), DIDS (IC50 = 31 microM), tamoxifen (IC50 = 1.3 microM)
      and mibefradil (IC50 = 7 microM) inhibited proliferative growth of AML12 as
      determined by cell counts over 4 days or by protein accumulation over 2 days.
      Only the inhibitory effects of NPPB and mibefradil reversed with the drug
      washout. Hyperosmolarity by added sucrose (50 and 100 mM) also inhibited cell
      proliferation. Of the hydrophobic inhibitors neither NPPB at 40 microM nor
      tamoxifen at 1.3 microM, added for 48 h, reduced cellular ATP; however, DIDS at
      31 microM significantly reduced cellular ATP with an equivalent increase in
      cellular ADP. We conclude that those membrane Cl- currents that can be activated
      by hypotonic stress are involved in mechanisms controlling liver cell growth, and
      that NPPB, tamoxifen and mibefradil at their IC50 for growth do not suppress the
      metabolism of mouse hepatocytes.

PMID- 11313438
TI  - Pregnenolone sulfate block of GABA(A) receptors: mechanism and involvement of a
      residue in the M2 region of the alpha subunit.
AB  - Neurosteroids are produced in the brain, and can have rapid actions on membrane
      channels of neurons. Pregnenolone sulfate (PS) is a sulfated neurosteroid which
      reduces the responses of the [gamma]-aminobutyric acid A (GABA(A)) receptor. We
      analysed the actions of PS on single-channel currents from recombinant GABA(A)
      receptors formed from [alpha]1, [beta]2 and [gamma]2L subunits. Currents were
      elicited by a concentration of GABA eliciting a half-maximal response (50 microM)
      and a saturating concentration (1 mM). PS reduced the duration of clusters of
      single-channel activity at either concentration of GABA. PS had no discernable
      effect on rapid processes: no effects were apparent on channel opening and
      closing, nor on GABA affinity, and a rapidly recovering desensitised state was
      not affected. Instead, PS produced a slowly developing block which occurred at a
      similar rate for receptors with open or closed channels and with one or two bound
      GABA molecules. The rate of block was independent of membrane potential, implying
      that the charged sulfate moiety does not move through the membrane field. Change
      in a specific residue near the intracellular end of the channel lining portion of
      the [alpha]1 subunit had a major effect on the rate of block. Mutation of the
      residue [alpha]1 V256S reduced the rate of block by 30-fold. A mutation at the
      homologous position of the [beta]2 subunit ([beta]2 A252S) had no effect, nor did
      a complementary mutation in the [gamma]2L subunit ([gamma]2L S266A). It seems
      likely that this residue is involved in a conformational change underlying block
      by PS, instead of forming part of the binding site for PS.

PMID- 11313439
TI  - Heterogeneous susceptibility of GABA(A) receptor-mediated IPSCs to depolarization
      induced suppression of inhibition in rat hippocampus.
AB  - Depolarization-induced suppression of inhibition (DSI) in central neurons is
      mediated by a transient reduction of [gamma]-aminobutyric acid (GABA) release
      from interneurons. DSI is induced by a retrograde signal emitted from principal
      cells. We used electrophysiological recordings from CA1 neurons of the rat
      hippocampal slice to test the hypothesis that only certain classes of
      interneurons are susceptible to DSI. DSI of action potential-dependent,
      spontaneous, inhibitory postsynaptic currents (sIPSCs) in hippocampus is
      facilitated by carbachol (3 microM), which increases the occurrence of large
      sIPSCs. Besides carbachol, noradrenaline (norepinephrine; 10 microM), or elevated
      extracellular potassium (8 mM), could abruptly increase the occurrence of large
      sIPSCs and DSI in many cases. DSI appeared and disappeared concomitantly with the
      onset and offset of these large sIPSCs. In contrast, application of AP-5 and CNQX
      often markedly increased baseline sIPSC activity without enhancing DSI. A brief
      train of extracellular electrical stimulation could trigger the onset of
      prolonged, repetitive IPSC activity that was susceptible to DSI. The magnitude of
      DSI of single evoked IPSCs (eIPSCs) in a given pyramidal cell could be altered by
      changes in stimulus strength, but there was no simple relationship between
      stimulus strength and DSI. Baclofen (0.5-5 microM) eliminated the increase in
      sIPSC activity and DSI induced by carbachol. A GABA(B)receptor antagonist, CGP
      35348, reversed the effects of baclofen. Carbachol-induced sIPSCs had relatively
      rapid rise and decay phases. There was no marked distinction between DSI
      susceptible and non-susceptible sIPSCs. Nevertheless, two kinetically distinct
      components of the eIPSC could be distinguished by their decay times. DSI reduced
      GABA(A),(fast) without affecting GABA(A),(slow). Furosemide (frusemide), which
      blocks only GABA(A),(fast), reduced the eIPSC and occluded DSI. The data suggest
      that, with respect to DSI, there are at least three functionally distinct types
      of IPSCs. Two types (one susceptible to DSI and one not) have relatively rapid
      kinetics are probably made by perisomatic synapses. A third, slow IPSC, which is
      insensitive to DSI, may be produced by distal dendritic synapses.

PMID- 11313440
TI  - Control of glutamate and GABA release by nociceptin/orphanin FQ in the rat
      lateral amygdala.
AB  - The actions of the heptadecapeptide termed nociceptin or orphanin FQ (N/OFQ) and
      the recently discovered putative precursor product nocistatin were examined on
      synaptic transmission in putative projection cells of the rat lateral amygdala
      using the whole-cell patch-clamp technique. N/OFQ decreased evoked non-NMDA
      receptor-mediated excitatory postsynaptic current (EPSC) amplitudes in a
      concentration-dependent manner, with a half-maximal inhibitory effect elicited by
      21.8 +/- 7.5 nM and a Hill coefficient of 0.8 +/- 0.2 (n = 22). Responses were
      maximally suppressed to 70.3 +/- 1.7 % of the control value. The effect of N/OFQ
      was prevented by 1 microM [Phe1[psi](CH2-NH)Gly2]NC(1-13)NH2 (Phe[psi]N/OFQ), a
      substance known as an antagonist/partial agonist of the ORL receptor. GABA(A)
      receptor-mediated inhibitory postsynaptic currents (IPSCs) elicited through intra
      amygdaloid stimulation were reduced to 48.0 +/- 6.8 % by 1 microM N/OFQ (n = 5).
      Nocistatin had no measurable effect on evoked synaptic currents or membrane
      properties of recorded neurons. N/OFQ reduced the frequency of spontaneous
      miniature EPSCs and IPSCs to 74.0 +/- 2.6 % and 84.4 +/- 1.1 %, respectively,
      without affecting the amplitudes. The present findings indicate that N/OFQ, but
      not nocistatin, inhibits the release of glutamate and GABA in the lateral
      amygdala, presumably by acting on presynaptic release sites. These mechanisms may
      add to the role of N/OFQ in reducing stress vulnerability as recently proposed on
      the basis of behavioural and genetic approaches.

PMID- 11313441
TI  - Seizure-like activity in the disinhibited CA1 minislice of adult guinea-pigs.
AB  - Spontaneous activity was monitored during pharmacological blockade of GABA(A)
      receptor function in the CA1 minislice (CA3 was cut off). Synaptic inhibition was
      blocked by competitive GABA(A) antagonists bicuculline-methiodide (Bic) or
      GABAZINE (GBZ) and the chloride channel blocker picrotoxin (PTX). Extra- and
      intracellular recordings using sharp electrodes were carried out in stratum
      radiatum and pyramidale. At low antagonist concentrations (Bic, GBZ: 1-10 microM;
      PTX: < 100 microM), synchronized bursts (< 500 ms in duration, interictal
      activity) were seen as described previously. However, in the presence of high
      concentrations (Bic, GBZ: 50-100 microM; PTX: 100-200 microM), seizure-like,
      ictal events (duration 4-17 s) were observed in 67 of 88 slices. No other
      experimental measures to increase excitability were applied: cation
      concentrations ([Ca2+]o = 2 mM, [Mg2+]o = 1.7 mM, [K+]o = 3 mM) and recording
      temperature (30-32 degrees C) were standard and GABA(B)-mediated inhibition was
      intact. In whole-slice recordings prominent interictal activity, but fewer ictal
      events were observed. A reduced ictal activity was also observed when interictal
      like responses were evoked by afferent stimulation. Ictal activity was reversibly
      blocked by antagonists of excitatory transmission, CNQX (40 microM) or D-AP5 (50
      microM). Disinhibition-induced ictal development did not rely on group I mGluR
      activation as it was not prevented in the presence of group I mGluR antagonists
      (AIDA or 4CPG). (RS)-3,5-DHPG prevented the induction and reversed the tertiary
      component of the ictal event through a group I mGluR-independent mechanism.

PMID- 11313442
TI  - Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic
      transmission in rat striatal neurons.
AB  - The striatum is a crucial site of action for the motor effects of cannabinoids
      (CBs). However, the electrophysiological consequences of activation of CB
      receptors on the striatal neurons have not been established. Here we report for
      the first time that the cannabimimetic aminoalkylindole WIN 55,212-2 and the
      endogenous cannabinoid anandamide substantially depress corticostriatal
      glutamatergic synaptic transmission onto striatal neurons in the brain slice
      preparation. The selective CB1 receptor antagonist SR 141716 effectively reversed
      this inhibition. WIN 55,212-2 significantly increased the paired-pulse
      facilitation of synaptically evoked EPSCs, while having no effect on the
      sensitivity of postsynaptic neurons to [alpha]-amino-3-hydroxy-5-methylisoxazole
      4-propionic acid. WIN 55,212-2 also reduced the frequency of spontaneous, action
      potential-dependent EPSCs (sEPSCs) without altering their amplitude distribution.
      Superfusion of WIN 55,212-2 elicited a membrane hyperpolarization accompanied by
      a decrease in input resistance. Both effects were blocked by intracellular
      caesium. In contrast, intracellular caesium failed to affect WIN 55,212-2
      mediated synaptic inhibition. The WIN 55,212-2-mediated synaptic inhibition was
      blocked by the Gi/o protein inhibitor pertussis toxin (PTX), but not by the
      GABA(A) receptor antagonist bicuculline or GABA(B) receptor antagonist SCH 50911.
      Pretreatment with the N-type Ca2+ channel antagonist [omega]-conotoxin GVIA
      selectively abolished the WIN-55,212-2-mediated synaptic inhibition. These
      results suggest that cannabinoids depress the corticostriatal glutamatergic
      synaptic transmission through the activation of presynaptic CB1 receptors to
      inhibit N-type Ca2+ channel activity, which in turn reduces glutamate release.
      The presynaptic action of cannabinoids is mediated by a PTX-sensitive Gi/o
      protein-coupled signalling pathway.

PMID- 11313444
TI  - Involvement of Rho-kinase and tyrosine kinase in hypotonic stress-induced ATP
      release in bovine aortic endothelial cells.
AB  - Hypotonic stress induces ATP release followed by Ca2+ oscillations in bovine
      aortic endothelial cells (BAECs). We have investigated the cellular mechanism of
      the hypotonic stress-induced ATP release. Hypotonic stress induced tyrosine
      phosphorylation of at least two proteins, of 110 and 150 kDa. Inhibition of
      tyrosine kinase by the tyrosine kinase inhibitors herbimycin A and tyrphostin 46
      prevented ATP release and ATP-mediated Ca2+ oscillations induced by hypotonic
      stress. ATP release was also inhibited by the pretreatment of the cells with
      botulinum toxin C3, and augmented by lysophosphatidic acid. Furthermore, pre
      treating the cells with Y-27632, a selective inhibitor of Rho-kinase, also
      suppressed the hypotonic stress-induced ATP release and Ca2+ oscillations,
      indicating that Rho-mediated activation of Rho-kinase may be involved in the
      hypotonic ATP release. Hypotonic stress also induced a transient rearrangement of
      the actin cytoskeleton, which was suppressed by the tyrosine kinase inhibitors Y
      27632 and cytochalasin B. However, pretreatment of the cell with cytochalasin B
      inhibited neither the hypotonic stress-induced ATP release nor the Ca2+
      oscillations. These results indicate that tyrosine kinase and the Rho-Rho-kinase
      pathways are involved in hypotonic stress-induced ATP release and actin
      rearrangement, but actin polymerization is not required for ATP release in BAECs.

PMID- 11313443
TI  - Evidence that nitric oxide- and opioid-containing interneurons innervate vessels
      in the dorsal horn of the spinal cord of rats.
AB  - In the dorsal horn of the spinal cord, activation of small fibre nociceptive
      afferents leads to the release of nitric oxide and enkephalins by interneurons.
      In this work we encountered unexpected relationships among local spinal cord
      dorsal horn blood flow, specific forms of afferent input, nitric oxide and
      intrinsic opioids. Selective rises in rat lumbar dorsal cord blood flow using
      laser Doppler flowmetry and microelectrode hydrogen clearance polarography were
      generated by ipsilateral, 'nociceptive' low (3 Hz) frequency stimulation of
      sciatic afferents. Inhibitors of nitric oxide synthase (NOS) prevented rises in
      flow during stimulation without influencing baseline flow. Ipsilateral hindpaw
      intradermal injection of capsaicin, a nociceptive activator, also generated large
      rises in flow sensitive to NOS inhibition. During NOS blockade or morphine
      administration there were unexpected acute declines in the dorsal cord blood flow
      strictly confined to low frequency stimulation epochs. This acute
      vasoconstrictive effect was prevented by administration of an opioid receptor
      antagonist. Using immunohistochemistry, terminals apparently innervating dorsal
      spinal cord blood vessels were labelled with antibodies against neuronal NOS and
      met-enkephalin. We conclude that local nitric oxide and opioids, probably from
      interneurons, have competitive actions on dorsal horn microvessels once
      interneurons are activated during a nociceptive barrage. Collateral innervation
      of blood vessels may explain this property.

PMID- 11313445
TI  - Sustained stimulation of exocytosis triggers continuous membrane retrieval in rat
      pituitary somatotrophs.
AB  - We studied the relationship between exocytosis and endocytosis in rat pituitary
      somatotrophs using patch-clamp capacitance, FM1-43 fluorescence imaging and
      amperometry. Stimulation of exocytosis through voltage-dependent Ca2+ channels by
      depolarizations (1-5 s) increased the capacitance by 4.3 +/- 0.9 % and the
      fluorescence by 6.6 +/- 1.1 % (10 cells). The correlation between the capacitance
      and fluorescence changes indicated that the cell membrane and granule membrane
      added via exocytosis were stained with the membrane-bound fluorescent dye FM1-43
      in a quantitatively similar manner. Intracellular dialysis (0.5-4.5 min) with
      elevated Ca2+ (1.5-100 microM) evoked continuous exocytosis that was detected
      with a carbon fibre electrode from dopamine-loaded cells (10 cells) or as an
      increase in FM1-43 fluorescence (56 +/- 10 %; 21 cells). Interestingly during
      Ca2+ dialysis the capacitance did not significantly change (2 +/- 1 %; 31 cells),
      indicating that endocytosis efficiently retrieved increased cell membrane.
      Sustained endocytosis was not blocked when the intracellular GTP (300 microM) was
      replaced with GTP[gamma]S. Replacing intracellular Ca2+ (100 microM) with Ba2+
      (300 microM) or Sr2+ (200 microM), or reducing the pH of the intracellular
      solution from 7.2 to 6.2 did not block sustained endocytosis. Our results suggest
      that pituitary somatotrophs have the ability to undergo continuous exocytosis and
      membrane retrieval that persist in whole-cell recordings.

PMID- 11313446
TI  - Integrin binding to fibronectin and vitronectin maintains the barrier function of
      isolated porcine coronary venules.
AB  - Integrin-mediated endothelial cell-extracellular matrix adhesion plays a critical
      role in maintaining the structural integrity of microvascular walls. The aim of
      this study was to evaluate the impact of specific integrin extracellular domain
      binding to matrix fibronectin and vitronectin on the barrier function of intact
      microvascular endothelium. The apparent permeability coefficient of albumin was
      measured in isolated and perfused porcine coronary venules using a fluorescence
      ratioing technique with the aid of fluorescence microscopy. Inhibition of
      integrin binding to either fibronectin with GRGDdSP peptide or vitronectin with
      GPenGRGDSPCA peptide dose-dependently increased venular permeability by 2- to 3
      fold. The effects were sustained for more than 60 min and were reversible upon
      clearance of the peptides. In contrast, the inactive control peptide GRADSP did
      not significantly affect venular permeability. Pretreatment of the venules with
      purified human fibronectin and vitronectin, respectively, prevented the
      hyperpermeability response to GRGDdSP and GPenGRGDSPCA. GRGDSP, a peptide that
      inhibits integrin binding to both fibronectin and vitronectin, produced an even
      higher permeability (4.5-fold) in venules than GRGDdSP or GPenGRGDSPCA alone, and
      the effect was blunted in vessels preincubated with both fibronectin and
      vitronectin. The results indicate the importance of integrin-matrix interaction
      in the physiological regulation of microvascular permeability. It is likely that
      both fibronectin and vitronectin binding to integrins contribute to the
      maintenance of endothelial barrier function in venules.

PMID- 11313447
TI  - A redox-based mechanism for the contractile and relaxing effects of NO in the
      guinea-pig gall bladder.
AB  - The purpose of this study was to determine the effects of sodium nitroprusside
      (SNP), 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NO) and 3
      morpholinosydnonimine (SIN-1), NO donors which yield different NO reactive
      species (NO+, NO* and peroxynitrite, respectively), as well as exogenous
      peroxynitrite, on gall bladder contractility. Under resting tone conditions, SNP
      induced a dose-dependent contraction with a maximal effect (10.3 +/- 0.7 mN,
      S.E.M.) at 1 mM. Consistent with these findings, SNP caused a concentration
      dependent depolarization of gall bladder smooth muscle. The excitatory effects of
      SNP were dependent on extracellular calcium entry through L-type Ca2+ channels.
      Furthermore, the contraction and depolarization were sensitive to tyrosine kinase
      blockade, and an associated increase in tyrosine phosphorylation was detected in
      Western blot studies. DETA/NO induced dose-dependent relaxing effects. These
      relaxations were sensitive to the guanylyl cyclase inhibitor 1H
      [1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one (ODQ, 2 microM) but they were not
      altered by treatment with the potassium channel blockers tetraethylammoniun (TEA,
      5 mM) and 4-aminopyridine (4-AP, 5 mM). When tested in a reducing environment
      (created by 2.5 mM 1,4-dithiothreitol, DTT), SNP caused a relaxation of gall
      bladder muscle strips. Similarly, the SNP-induced contraction was converted to a
      relaxation, and associated hyperpolarization, when DTT was added during the
      steady state of an SNP-induced response. SIN-1 (0.1 mM), which has been shown to
      release peroxynitrite, induced relaxing effects that were enhanced by superoxide
      dismutase (SOD, 50 U ml(-1)). The relaxations induced by either SIN-1 alone or
      SIN-1 in the presence of SOD were strengthened by catalase (1000 U ml(-1)) and
      abolished by ODQ pretreatment. However, exogenous peroxynitrite induced a
      concentration-dependent contraction, which was dependent on activation of
      leukotriene (LT) metabolism and extracellular calcium. The peroxynitrite-induced
      contraction was abolished in the presence of the peroxynitrite scavenger
      melatonin. These results suggest that SIN-1 behaves as an NO* rather than a
      peroxynitrite source. We conclude that, depending on the redox state, NO has
      opposing effects on the motility of the gall bladder, being a relaxing agent when
      in NO * form and a contracting agent when in NO+ or peroxynitrite redox species
      form. Knowledge of the contrasting effects of the different redox forms of NO can
      clarify our understanding of the effects of NO donors on gall bladder and other
      smooth muscle cell types.

PMID- 11313448
TI  - Spino-bulbo-spinal pathway mediating vagal modulation of nociceptive
      neuroendocrine control of inflammation in the rat.
AB  - Stimulation of nociceptors by intradermal capsaicin produces depression of
      bradykinin (BK)-induced synovial plasma extravasation (PE) that is markedly
      enhanced by subdiaphragmatic vagotomy. This depression is mediated by the adrenal
      medullae, a propriospinal pathway between the afferent nociceptive input and
      preganglionic neurones projecting to the adrenal medullae, and a spino-bulbo
      spinal pathway. Here we investigated the role of spinal ascending and descending
      pathways in the interaction between noxious and vagal afferent inputs, leading to
      inhibition of BK-induced PE mediated by the adrenal medullae. Nociceptors in the
      paw were activated by capsaicin and depression of BK-induced PE was measured in
      rats with intact or cut subdiaphragmatic vagus nerves. After cutting the
      dorsolateral funiculus (DLF) contralateral to the stimulated hindpaw (segmental
      level C5/C6 and T8/T9), depression of BK-induced PE was weak or absent both in
      rats with intact vagus nerves and in vagotomised rats, suggesting that an
      ascending excitatory pathway was interrupted. After cutting the DLF ipsilateral
      to the stimulated hindpaw, depression of BK-induced PE was already markedly
      enhanced, even in the absence of vagotomy. Ipsilateral DLF lesion (L2/L3) below
      the level of the spinal output to the adrenal medullae produced the same effect,
      suggesting interruption of a descending inhibitory pathway that relays the effect
      of vagal activity to the level of the capsaicin-induced nociceptive input.
      Contralateral and ipsilateral hemisection of the spinal cord (C5/C6) produced the
      same changes as the corresponding DLF lesions. Ipsi- or contralateral lesion of
      the dorsal funiculus at the spinal level T8/T9 had no effect on depression of BK
      induced PE generated by cutaneous noxious stimulation of the forepaw. We suggest
      that noxious stimulation activates an ascending pathway of the spino-bulbo-spinal
      excitatory circuit which projects through the DLF contralateral to the
      nociceptive input, and that the inhibitory pathway which is activated by vagal
      afferent activity projects through the DLF ipsilateral to the nociceptive input.

PMID- 11313449
TI  - Potentiation of sensory responses in the anterior cingulate cortex following
      digit amputation in the anaesthetised rat.
AB  - The anterior cingulate cortex (ACC) is important for processing different types
      of information, including sensory inputs. In the present study on anaesthetised
      rats, we recorded in vivo sensory responses of the ACC to peripheral electrical
      shocks. Peripheral electrical stimulation at high intensities sufficient to
      activate nociceptive sensory fibres elicited EPSPs within the ACC. Digit
      amputation caused long-lasting potentiation of ACC responses to peripheral
      electrical stimulation. Evoked field EPSPs remained enhanced for at least 120 min
      after the amputation. Because electrical shocks were delivered to the normal
      hindpaw, it is likely that plastic changes occur centrally in the spinal cord or
      the supraspinal structures following amputation. We also recorded field EPSPs of
      the ACC in response to focal cortical stimulation within the ACC. Like the
      sensory responses, field EPSPs produced by focal cortical stimulation within the
      ACC were potentiated after digit amputation, suggesting that long-lasting changes
      occurred locally within the ACC. Local blockade of peripheral activity by QX-314
      at the amputated hindpaw 120 min after amputation did not significantly affect
      sensory responses induced within the ACC. Thus, peripheral ongoing inputs do not
      play an important role in maintaining potentiation within the ACC. Two pulses of
      hindpaw stimulation caused paired-pulse depression in the ACC. Local stimulation
      within the ACC also caused depression of sensory responses to hindpaw
      stimulation, suggesting that the population of synapses activated by local
      stimulation may overlap with that activated by peripheral hindpaw stimulation.
      Our results suggest that rapid enhancement of sensory responses can be observed
      in the ACC after amputation and that enhanced neuronal responses to subsequent
      somatosensory stimuli may contribute to phantom-limb pain.

PMID- 11313450
TI  - Size of myelinated nerve fibres is not increased by expansion of the peripheral
      field in cats.
AB  - This study tests the hypothesis that target size regulates the size of myelinated
      sensory and motor fibres in peripheral nerves. Cat medial gastrocnemius (MG)
      muscles were partially denervated and the size of the remaining nerve fibres that
      sprouted was examined 6.4 +/- 0.9 months later to determine whether nerve fibre
      size increased with target size. Electrophysiological and morphometric analyses
      were used to quantify myelinated nerve fibre size. Charge measurements from
      dorsal and ventral roots were used to electrophysiologically quantify the
      relative number of cut nerve fibres and the average size of the remaining intact
      sensory and motor nerve fibres. Medial gastrocnemius muscle and motor unit forces
      provided indirect measurements of the increase in target size. Conduction
      velocities and amplitude of unitary action potentials of motor nerve fibres
      innervating single motor units were also measured after partial denervation.
      Electrophysiological measurements of nerve fibre size and morphometric
      measurements of outer fibre perimeters and fibre areas concurred and demonstrated
      that myelinated nerve fibres supplying partially denervated MG muscles did not
      increase in size in parallel with the increase in the target size. Thus, unlike
      non-myelinated nerve fibres, the size of myelinated nerve fibres does not
      increase as target size increases. Retrograde control of size in non-myelinated
      but not in myelinated nerve fibres demonstrates differences in plasticity of
      neurons in the somatic and autonomic nervous systems.

PMID- 11313451
TI  - Variability in the control of head movements in seated humans: a link with
      whiplash injuries?
AB  - The aim of this study was to determine how context and on-line sensory
      information are combined to control posture in seated subjects submitted to high
      jerk, passive linear accelerations. Subjects were seated with eyes closed on a
      servo-controlled linear sled. They were asked to relax and received brief
      accelerations either sideways or in the fore-aft direction. The stimuli had an
      abrupt onset, comparable to the jerk experienced during a minor car collision.
      Rotation and translation of the head and body were measured using an Optotrak
      system. In some of the subjects, surface electromyographic (EMG) responses of
      selected neck and/or back muscles were recorded simultaneously. For each subject,
      responses were highly stereotyped from the first trial, and showed little sign of
      habituation or sensitisation. Comparable results were obtained with sideways and
      fore-aft accelerations. During each impulse, the head lagged behind the trunk for
      several tens of milliseconds. The subjects' head movement responses were
      distributed as a continuum in between two extreme categories. The 'stiff'
      subjects showed little rotation or translation of the head relative to the trunk
      for the whole duration of the impulse. In contrast, the 'floppy' subjects showed
      a large roll or pitch of the head relative to the trunk in the direction opposite
      to the sled movement. This response appeared as an exaggerated 'inertial'
      response to the impulse. Surface EMG recordings showed that most of the stiff
      subjects were not contracting their superficial neck or back muscles. We think
      they relied on bilateral contractions of their deep, axial musculature to keep
      the head-neck ensemble in line with the trunk during the movement. About half of
      the floppy subjects displayed reflex activation of the neck muscles on the side
      opposite to the direction of acceleration, which occurred before or during the
      head movement and tended to exaggerate it. The other floppy subjects seemed to
      rely on only the passive biomechanical properties of their head-neck ensemble to
      compensate for the perturbation. In our study, proprioception was the sole source
      of sensory information as long as the head did not move. We therefore presume
      that the EMG responses and head movements we observed were mainly triggered by
      the activation of stretch receptors in the hips, trunk and/or neck. The
      visualisation of an imaginary reference in space during sideways impulses
      significantly reduced the head roll exhibited by floppy subjects. This suggests
      that the adoption by the central nervous system of an extrinsic, 'allocentric'
      frame of reference instead of an intrinsic, 'egocentric' one may be instrumental
      for the selection of the stiff strategy. The response of floppy subjects appeared
      to be maladaptive and likely to increase the risk of whiplash injury during motor
      vehicle accidents. Evolution of postural control may not have taken into account
      the implications of passive, high-acceleration perturbations affecting seated
      subjects.

PMID- 11313452
TI  - Foot sole and ankle muscle inputs contribute jointly to human erect posture
      regulation.
AB  - In order to assess the relative contribution and the interactions of the plantar
      cutaneous and muscle proprioceptive feedback in controlling human erect posture,
      single or combined vibratory stimuli were applied to the forefoot areas and to
      the tendons of the tibialis anterior muscles of nine standing subjects using
      various vibration frequency patterns (ranging from 20 to 80 Hz). The variations
      in the centre of foot pressure, ankle angle and the EMG activities of the soleus
      and tibialis anterior muscles of each subject were recorded and analysed.
      Separate stimulation of the plantar forefoot zones or the tibialis anterior
      muscles always resulted in whole-body tilts oppositely directed backwards and
      forwards, respectively, the amplitude of which was proportional to the vibration
      frequency. EMG activity of ankle muscles also varied according to the direction
      of the postural responses. However, the same vibration frequency did not elicit
      equivalent postural responses: in the low frequency range, tactile stimulation
      induced stronger postural effects than proprioceptive stimulation, and the
      converse was the case for the higher frequency range. Under sensory conflict
      conditions, i.e. foot sole-flexor ankle muscle co-stimulation, the direction of
      the body tilts also varied according to the difference and the absolute levels of
      the vibration frequencies. In all cases, the resulting postural shifts always
      corresponded to the theoretical sum of the isolated effects observed upon
      vibrating each of these two sensory channels. We proposed that tactile and
      proprioceptive information from the foot soles and flexor ankle muscles might be
      co-processed following a vector addition mode to subserve the maintenance of
      erect stance in a complementary way.

PMID- 11313453
TI  - Human balancing of an inverted pendulum: is sway size controlled by ankle
      impedance?
AB  - Using the ankle musculature, subjects balanced a large inverted pendulum. The
      equilibrium of the pendulum is unstable and quasi-regular sway was observed like
      that in quiet standing. Two main questions were addressed. Can subjects
      systematically change sway size in response to instruction and availability of
      visual feedback? If so, do subjects decrease sway size by increasing ankle
      impedance or by some alternative mechanism? The position of the pendulum, the
      torque generated at each ankle and the soleus and tibialis anterior EMG were
      recorded. Results showed that subjects could significantly reduce the mean sway
      size of the pendulum by giving full attention to that goal. With visual feedback
      sway size could be minimised significantly more than without visual feedback. In
      changing sway size, the frequency of the sways was not changed. Results also
      revealed that ankle impedance and muscle co-contraction were not significantly
      changed when the sway size was decreased. As the ankle impedance and sway
      frequency do not change when the sway size is decreased, this implies no change
      in ankle stiffness or viscosity. Increasing ankle impedance, stiffness or
      viscosity are not the only methods by which sway size could be reduced. A
      reduction in torque noise or torque inaccuracy via a predictive process which
      provides active damping could reduce sway size without changing ankle impedance
      and is plausible given the data. Such a strategy involving motion recognition and
      generation of an accurate motor response may require higher levels of control
      than changing ankle impedance by altering reflex or feedforward gain.

PMID- 11313454
TI  - Polypyrimidine tract binding protein antagonizes exon definition.

PMID- 11313455
TI  - Fission yeast Rad17 associates with chromatin in response to aberrant genomic
      structures.
AB  - Fission yeast checkpoint protein Rad17 is required for the DNA integrity
      checkpoint responses. A fraction of Rad17 is chromatin bound independent of the
      other checkpoint proteins throughout the cell cycle. Here we show that in
      response to DNA damage induced by either methyl methanesulfonate treatment or
      ionizing radiation, increased levels of Rad17 bind to chromatin. Following S
      phase stall induced by hydroxyurea or a cdc22 mutation, the chromatin-bound Rad17
      progressively dissociates from the chromatin. After S-phase arrest by hydroxyurea
      in cds1Delta or rad3Delta cells or by replication mutants, Rad17 remains
      chromatin bound. Rad17 is able to complex in vivo with an Rfc small subunit,
      Rfc2, but not with Rfc1. Furthermore, cells with rfc1Delta are checkpoint
      proficient, suggesting that Rfc1 does not have a role in checkpoint function. A
      checkpoint-defective mutant protein, Rad17(K118E), which has similar nuclear
      localization to that of the wild type, is unable to bind ATP and has reduced
      ability in chromatin binding. Mutant Rad17(K118E) protein also has reduced
      ability to complex with Rfc2, suggesting that Lys(118) of Rad17 plays a role in
      Rad17-Rfc small-subunit complex formation and chromatin association. However, in
      the rad17.K118E mutant cells, Cds1 can be activated by hydroxyurea. Together,
      these results suggest that Rad17 binds to chromatin in response to an aberrant
      genomic structure generated from DNA damage, replication mutant arrest, or
      hydroxyurea arrest in the absence of Cds1. Rad17 is not required to bind
      chromatin when genomic structures are protected by hydroxyurea-activated Cds1.
      The possible checkpoint events induced by chromatin-bound Rad17 are discussed.

PMID- 11313456
TI  - Mechanism for mutational inactivation of the tumor suppressor Smad2.
AB  - Transforming growth factor beta (TGF-beta) is a potent natural antiproliferative
      agent that plays an important role in suppressing tumorigenicity. In numerous
      tumors, loss of TGF-beta responsiveness is associated with inactivating mutations
      that can occur in components of this signaling pathway, such as the tumor
      suppressor Smad2. Although a general framework for how Smads transduce TGF-beta
      signals has been proposed, the physiological relevance of alterations of Smad2
      functions in promoting tumorigenesis is still unknown. Here, we show that
      expression of Smad2.P445H, a tumor-derived mutation of Smad2 found in human
      cancer, suppresses the ability of the Smads to mediate TGF-beta-induced growth
      arrest and transcriptional responses. Smad2.P445H is phosphorylated by the
      activated TGF-beta receptor at the carboxy-terminal serine residues and
      associates with Smad3 and Smad4 but is unable to dissociate from the receptor.
      Upon ligand-induced phosphorylation, Smad2.P445H interacts stably with wild-type
      Smad2, thereby blocking TGF-beta-induced nuclear accumulation of wild-type Smad2
      and Smad2-dependent transcription. The ability of the Smad2.P445H to block the
      nuclear accumulation of wild-type Smad2 protein reveals a new mechanism for loss
      of sensitivity to the growth-inhibitory functions of TGF-beta in tumor
      development.

PMID- 11313457
TI  - Common properties of nuclear body protein SP100 and TIF1alpha chromatin factor:
      role of SUMO modification.
AB  - The SP100 protein, together with PML, represents a major constituent of the PML
      SP100 nuclear bodies (NBs). The function of these ubiquitous subnuclear
      structures, whose integrity is compromised in pathological situations such as
      acute promyelocytic leukemia (APL) or DNA virus infection, remains poorly
      understood. There is little evidence for the occurrence of actual physiological
      processes within NBs. The two NB proteins PML and SP100 are covalently modified
      by the ubiquitin-related SUMO-1 modifier, and recent work indicates that this
      modification is critical for the regulation of NB dynamics. In exploring the
      functional relationships between NBs and chromatin, we have shown previously that
      SP100 interacts with members of the HP1 family of nonhistone chromosomal proteins
      and that a variant SP100 cDNA encodes a high-mobility group (HMG1/2) protein.
      Here we report the isolation of a further cDNA, encoding the SP100C protein, that
      contains the PHD-bromodomain motif characteristic of chromatin proteins. We
      further show that TIF1alpha, a chromatin-associated factor with homology to both
      PML and SP100C, is also modified by SUMO-1. Finally, in vitro experiments
      indicate that SUMO modification of SP100 enhances the stability of SP100-HP1
      complexes. Taken together, our results suggest an association of SP100 and its
      variants with the chromatin compartment and, further, indicate that SUMO
      modification may play a regulatory role in the functional interplay between the
      nuclear bodies and chromatin.

PMID- 11313458
TI  - Transcriptional repression by RB-E2F and regulation of anchorage-independent
      survival.
AB  - Mutations that lead to anchorage-independent survival are a hallmark of tumor
      cells. Adhesion of integrin receptors to extracellular matrix activates a
      survival signaling pathway in epithelial cells where Akt phosphorylates and
      blocks the activity of proapoptotic proteins such as the BCL2 family member Bad,
      the forkhead transcription factor FKHRL-1, and caspase 9. Insulin-like growth
      factor 1 (IGF-1) is a well-established epithelial cell survival factor that also
      triggers activation of Akt and can maintain Akt activity after cells lose matrix
      contact. It is not until IGF-1 expression diminishes (~16 h after loss of matrix
      contact) that epithelial cells deprived of matrix contact undergo apoptosis. This
      suggests that IGF-1 expression is linked to cell adhesion and that it is the loss
      of IGF-1 which dictates the onset of apoptosis after cells lose matrix contact.
      Here, we examine the linkage between cell adhesion and IGF-1 expression. While
      IGF-1 is able to maintain Akt activity and phosphorylation of proapoptotic
      proteins in cells that have lost matrix contact, Akt is not able to phosphorylate
      and inactivate another of its substrates, glycogen synthase kinase 3beta (GSK
      3beta), under these conditions. The reason for this appears to be a rapid
      translocation of active Akt away from GSK-3beta when cells lose matrix contact.
      One target of GSK-3beta is cyclin D, which is turned over in response to this
      phosphorylation. Therefore, cyclin D is rapidly lost when cells are deprived of
      matrix contact, leading to a loss of cyclin-dependent kinase 4 activity and
      accumulation of hypophosphorylated, active Rb. This facilitates assembly of a
      repressor complex containing histone deacetylase (HDAC), Rb, and E2F that blocks
      transcription of the gene for IGF-1, leading to loss of Akt activity,
      accumulation of active proapoptotic proteins, and apoptosis. This feedback loop
      containing GSK-3beta, cyclin D, HDAC-Rb-E2F, and IGF-1 then determines how long
      Akt will remain active after cells lose matrix contact, and thus it serves to
      regulate the onset of apoptosis in such cells.

PMID- 11313459
TI  - Hypoxia extends the life span of vascular smooth muscle cells through telomerase
      activation.
AB  - Chronic hypoxia induces smooth muscle cell proliferation and vessel wall
      remodeling in the vasculature of the lung. One well-characterized component of
      the hypoxic response is transcriptional activation of genes encoding vascular
      smooth muscle cell (VSMC) mitogens. We report here that chronic hypoxia can also
      prolong the growth of human VSMC by inducing telomerase activity and telomere
      stabilization. We demonstrate that hypoxia induced phosphorylation of the
      telomerase catalytic component (TERT) and sustained high levels of TERT protein
      expression in VSMC compared to normoxia. Furthermore, inhibition of telomerase
      shortened cell life span in hypoxic cultures, whereas constitutive expression of
      TERT extended the life span of cells under normoxic conditions. Our data indicate
      that hypoxic induction of telomerase activity could be involved in long-term
      growth of VSMC and may thus contribute to human vascular disorders.

PMID- 11313460
TI  - Six4, a putative myogenin gene regulator, is not essential for mouse embryonal
      development.
AB  - Six4 is a member of the Six family genes, homologues of Drosophila melanogaster
      sine oculis. The gene is thought to be involved in neurogenesis, myogenesis, and
      development of other organs, based on its specific expression in certain neuronal
      cells of the developing embryo and in adult skeletal muscles. To elucidate the
      biological roles of Six4, we generated Six4-deficient mice by replacing the Six
      homologous region and homeobox by the beta-galactosidase gene. 5-Bromo-4-chloro-3
      indolyl-beta-D-galactopyranoside staining of the heterozygous mutant embryos
      revealed expression of Six4 in cranial and dorsal root ganglia, somites, otic and
      nasal placodes, branchial arches, Rathke's pouch, apical ectodermal ridges of
      limb buds, and mesonephros. The expression pattern was similar to that of Six1
      except at the early stage of embryonic day 8.5. Six4-deficient mice were born
      according to the Mendelian rule with normal gross appearance and were fertile. No
      hearing defects were detected. Six4-deficient embryos showed no morphological
      abnormalities, and the expression patterns of several molecular markers, e.g.,
      myogenin and NeuroD3 (neurogenin1), were normal. Our results indicate that Six4
      is not essential for mouse embryogenesis and suggest that other members of the
      Six family seem to compensate for the loss of Six4.

PMID- 11313461
TI  - A single point mutation in the V3 region affects protein kinase Calpha targeting
      and accumulation at cell-cell contacts.
AB  - Given the importance of intercellular adhesion for many regulatory processes, we
      have investigated the control of protein kinase Calpha (PKCalpha) targeting to
      the cell-cell contacts. We have previously shown that, upon treatment of the
      pituitary cell line GH3B6 with thyrotropin-releasing hormone (TRH) or phorbol 12
      myristate 13-acetate (PMA), human PKCalpha (hPKCalpha) is selectively targeted to
      the cell-cell contacts (42). Here we show that the D294G mutation of hPKCalpha,
      previously identified in a subpopulation of human tumors, induces the loss of
      this selective targeting. The D294G mutant is instead targeted to the entire
      plasma membrane, including the cell-cell contacts, and the duration of the first
      rapid and transient translocation induced by TRH (42) is longer than that of the
      wild-type enzyme (93.3 versus 22.5 s), coinciding with the duration of the
      [Ca(2+)](i) increase. We found that in the presence or absence of PMA, RACK1 is
      never localized at the cell-cell contacts nor was it coimmunoprecipitated with
      hPKCalpha wild type or the D294G mutant. In contrast, PMA treatment or long-term
      TRH stimulation resulted in the presence of F-actin and beta-catenin at the cell
      cell contacts and their exclusion from the rest of the plasma membrane. Upon
      disruption of the F-actin network with phalloidin or cytochalasin D, wild-type
      hPKCalpha translocates but did not accumulate at the plasma membrane and beta
      catenin did not accumulate at the cell-cell contacts. In contrast, the disruption
      of the F-actin network affected neither translocation nor accumulation of the
      D294G mutant. These results show that the presence of PKCalpha at the cell-cell
      contacts is a regulated process which depends upon the integrity of both PKCalpha
      and the actin microfilament network.

PMID- 11313462
TI  - Protein factor requirements of the Apaf-1 internal ribosome entry segment: roles
      of polypyrimidine tract binding protein and upstream of N-ras.
AB  - It has been reported previously that the 5' untranslated region of the mRNA
      encoding Apaf-1 (apoptotic protease-activating factor 1) has an internal ribosome
      entry site (IRES), whose activity varies widely among different cell types. Here
      it is shown that the Apaf-1 IRES is active in rabbit reticulocyte lysates,
      provided that the system is supplemented with polypyrimidine tract binding
      protein (PTB) and upstream of N-ras (unr), two cellular RNA binding proteins
      previously identified to be required for rhinovirus IRES activity. In UV cross
      linking assays and electrophoretic mobility shift assays with individual
      recombinant proteins, the Apaf-1 IRES binds unr but not PTB; however, PTB binding
      occurs if unr is present. Over a range of different cell types there is a broad
      correlation between the activity of the Apaf-1 IRES and their content of PTB and
      unr. In cell lines deficient in these proteins, overexpression of PTB and unr
      stimulated Apaf-1 IRES function. This is the first example where an IRES in a
      cellular mRNA has been shown to be functionally dependent, both in vitro and in
      vivo, on specific cellular RNA binding proteins. Given the critical role of Apaf
      1 in apoptosis, these results have important implications for the control of the
      apoptotic cascade.

PMID- 11313463
TI  - Kinetics of p53 binding to promoter sites in vivo.
AB  - Downstream target genes of p53 are thought to mediate its tumor-suppressive
      activity, but it is unknown whether differential transactivation of these genes
      is regulated at the level of p53 binding to their promoters. To address this
      issue, p53 binding in vivo to consensus sites in the p21(Waf1), MDM2, and PIG3
      promoters was investigated in cells exposed to adriamycin (ADR) or ionizing
      radiation as well as in an inducible p53 cell line. p53-DNA complexes were cross
      linked in vivo by treating the cells with formaldehyde and processed by chromatin
      immunoprecipitation-PCR. This methodology allowed for the analysis of relevant
      p53-DNA complexes by preventing redistribution of cellular components upon
      collection of cell extracts. Increased p53 binding to the p21(Waf1), MDM2, and
      PIG3 promoters occurred within 2 h after p53 activation; however, significant
      increases in PIG3 transcription did not occur until 15 h after p53 binding. Gel
      shift analyses indicated that p53 had lower affinity for the consensus binding
      site in the PIG3 promoters compared to its consensus sites in the p21 and MDM2
      genes, which suggests that additional factors may be required to stabilize the
      interaction of p53 with the PIG3 promoter. Further, acetylated p53 (Lys382) was
      found in chemically cross-linked complexes at all promoter sites examined after
      treatment of cells with ADR. In summary, the kinetics of p53 binding in vivo to
      target gene regulatory regions does not uniformly correlate with target gene mRNA
      expression for the p53 target genes examined. Our results suggest that target
      genes with low-affinity p53 binding sites may require additional events and will
      have delayed kinetics of induction compared to those with high-affinity binding
      sites.

PMID- 11313464
TI  - JAK2 activates TFII-I and regulates its interaction with extracellular signal
      regulated kinase.
AB  - TFII-I is a transcription factor that shuttles between the cytoplasm and nucleus
      and is regulated by serine and tyrosine phosphorylation. Tyrosine phosphorylation
      of TFII-I can be regulated in a signal-dependent manner in various cell types. In
      B lymphocytes, Bruton's tyrosine kinase has been identified as a TFII-I tyrosine
      kinase. Here we report that JAK2 can phosphorylate and regulate TFII-I in
      nonlymphoid cells. The activity of TFII-I on the c-fos promoter in response to
      serum can be abolished by dominant negative JAK2 or the specific JAK2 kinase
      inhibitor AG490. Consistent with this, we have also found that JAK2 is activated
      by serum stimulation of fibroblasts. Tyrosine 248 of TFII-I is phosphorylated in
      vivo upon serum stimulation or JAK2 overexpression, and mutation of tyrosine 248
      to phenylalanine inhibits the ability of JAK2 to phosphorylate TFII-I in vitro.
      Tyrosine 248 of TFII-I is required for its interaction with and phosphorylation
      by ERK and its in vivo activity on the c-fos promoter. These results indicate
      that the interaction between TFII-I and ERK, which is essential for its activity,
      can be regulated by JAK2 through phosphorylation of TFII-I at tyrosine 248. Thus,
      like the STAT factors, TFII-I is a direct substrate of JAK2 and a signal
      dependent transcription factor that integrates signals from both tyrosine kinase
      and mitogen-activated protein kinase pathways to regulate transcription.

PMID- 11313465
TI  - Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation
      of fission yeast checkpoint kinase Cds1.
AB  - Fission yeast Cds1 is phosphorylated and activated when DNA replication is
      interrupted by nucleotide starvation or DNA damage. Cds1 enforces the S-M
      checkpoint that couples mitosis (M) to the completion of DNA synthesis (S). Cds1
      also controls replicational stress tolerance mechanisms. Cds1 is regulated by a
      group of proteins that includes Rad3, a kinase related to human checkpoint kinase
      ATM (ataxia telangiectasia mutated). ATM phosphorylates serine or threonine
      followed by glutamine (SQ or TQ). Here we show that in vitro, Rad3 and ATM
      phosphorylate the N-terminal domain of Cds1 at the motif T(11)Q(12). Substitution
      of threonine-11 with alanine (T11A) abolished Cds1 activation that occurs when
      DNA replication is inhibited by hydroxyurea (HU) treatment. The cds1-T11A mutant
      was profoundly sensitive to HU, although not quite as sensitive as a cds1(-) null
      mutant. Cds1(T11A) was unable to enforce the S-M checkpoint. These results
      strongly suggest that Rad3-dependent phosphorylation of Cds1 at threonine-11 is
      required for Cds1 activation and function.

PMID- 11313466
TI  - Nuclear export of 60s ribosomal subunits depends on Xpo1p and requires a nuclear
      export sequence-containing factor, Nmd3p, that associates with the large subunit
      protein Rpl10p.
AB  - Nuclear export of ribosomes requires a subset of nucleoporins and the Ran system,
      but specific transport factors have not been identified. Using a large subunit
      reporter (Rpl25p-eGFP), we have isolated several temperature-sensitive ribosomal
      export (rix) mutants. One of these corresponds to the ribosomal protein Rpl10p,
      which interacts directly with Nmd3p, a conserved and essential protein associated
      with 60S subunits. We find that thermosensitive nmd3 mutants are impaired in
      large subunit export. Strikingly, Nmd3p shuttles between the nucleus and
      cytoplasm and is exported by the nuclear export receptor Xpo1p. Moreover, we show
      that export of 60S subunits is Xpo1p dependent. We conclude that nuclear export
      of 60S subunits requires the nuclear export sequence-containing nonribosomal
      protein Nmd3p, which directly binds to the large subunit protein Rpl10p.

PMID- 11313467
TI  - Protein binding protects sites on stable episomes and in the chromosome from de
      novo methylation.
AB  - We have utilized the Escherichia coli lac repressor-operator system to test
      whether protein binding can interfere with de novo DNA methylation in mammalian
      cells. We find that a DNA binding protein can protect sites on the episome as
      well as in the genome from the de novo methylation activity of Dnmt3a.
      Transcriptional machinery moving through the binding sites does not affect the de
      novo methylation of these sites, and it does not affect the binding protein
      protection of these sites from de novo methylation. This study and previous
      studies provide a possible mechanism for the observation that an Sp1 site can
      serve as a cis-acting signal for demethylation and for preventing de novo
      methylation of the CpG island upstream of the mouse adenine
      phosphoribosyltransferase (Aprt) gene. These findings also support the hypothesis
      that protein binding may play a crucial role in changes of CpG methylation
      pattern in mammalian cells.

PMID- 11313468
TI  - Evidence for biased holliday junction cleavage and mismatch repair directed by
      junction cuts during double-strand-break repair in mammalian cells.
AB  - In mammalian cells, several features of the way homologous recombination occurs
      between transferred and chromosomal DNA are consistent with the double-strand
      break repair (DSBR) model of recombination. In this study, we examined the
      segregation patterns of small palindrome markers, which frequently escape
      mismatch repair when encompassed within heteroduplex DNA formed in vivo during
      mammalian homologous recombination, to test predictions of the DSBR model, in
      particular as they relate to the mechanism of crossover resolution. According to
      the canonical DSBR model, crossover between the vector and chromosome results
      from cleavage of the joint molecule in two alternate sense modes. The two
      crossover modes lead to different predicted marker configurations in the
      recombinants, and assuming no bias in the mode of Holliday junction cleavage, the
      two types of recombinants are expected in equal frequency. However, we propose a
      revision to the canonical model, as our results suggest that the mode of
      crossover resolution is biased in favor of cutting the DNA strands upon which DNA
      synthesis is occurring during formation of the joint molecule. The bias in
      junction resolution permitted us to examine the potential consequences of
      mismatch repair acting on the DNA breaks generated by junction cutting. The
      combination of biased junction resolution with both early and late rounds of
      mismatch repair can explain the marker patterns in the recombinants.

PMID- 11313469
TI  - Transcription factor HIF-1 is a necessary mediator of the pasteur effect in
      mammalian cells.
AB  - The ability to respond to differential levels of oxygen is important to all
      respiring cells. The response to oxygen deficiency, or hypoxia, takes many forms
      and ranges from systemic adaptations to those that are cell autonomous. Perhaps
      the most ancient of the cell-autonomous adaptations to hypoxia is a metabolic
      one: the Pasteur effect, which includes decreased oxidative phosphorylation and
      an increase in anaerobic fermentation. Because anaerobic fermentation produces
      far less ATP than oxidative phosphorylation per molecule of glucose, increased
      activity of the glycolytic pathway is necessary to maintain free ATP levels in
      the hypoxic cell. Here, we present genetic and biochemical evidence that, in
      mammalian cells, this metabolic switch is regulated by the transcription factor
      HIF-1. As a result, cells lacking HIF-1alpha exhibit decreased growth rates
      during hypoxia, as well as decreased levels of lactic acid production and
      decreased acidosis. We show that this decrease in glycolytic capacity results in
      dramatically lowered free ATP levels in HIF-1alpha-deficient hypoxic cells. Thus,
      HIF-1 activation is an essential control element of the metabolic state during
      hypoxia; this requirement has important implications for the regulation of cell
      growth during development, angiogenesis, and vascular injury.

PMID- 11313470
TI  - Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing
      irradiation.
AB  - Cell cycle arrests in the G(1), S, and G(2) phases occur in mammalian cells after
      ionizing irradiation and appear to protect cells from permanent genetic damage
      and transformation. Though Brca1 clearly participates in cellular responses to
      ionizing radiation (IR), conflicting conclusions have been drawn about whether
      Brca1 plays a direct role in cell cycle checkpoints. Normal Nbs1 function is
      required for the IR-induced S-phase checkpoint, but whether Nbs1 has a definitive
      role in the G(2)/M checkpoint has not been established. Here we show that Atm and
      Brca1 are required for both the S-phase and G(2) arrests induced by ionizing
      irradiation while Nbs1 is required only for the S-phase arrest. We also found
      that mutation of serine 1423 in Brca1, a target for phosphorylation by Atm,
      abolished the ability of Brca1 to mediate the G(2)/M checkpoint but did not
      affect its S-phase function. These results clarify the checkpoint roles for each
      of these three gene products, demonstrate that control of cell cycle arrests must
      now be included among the important functions of Brca1 in cellular responses to
      DNA damage, and suggest that Atm phosphorylation of Brca1 is required for the
      G(2)/M checkpoint.

PMID- 11313471
TI  - DR3 regulates negative selection during thymocyte development.
AB  - DR3 (Ws1, Apo3, LARD, TRAMP, TNFSFR12) is a member of the death domain-containing
      tumor necrosis factor receptor (TNFR) superfamily, members of which mediate a
      variety of developmental events including the regulation of cell proliferation,
      differentiation, and apoptosis. We have investigated the in vivo role(s) of DR3
      by generating mice congenitally deficient in the expression of the DR3 gene. We
      show that negative selection and anti-CD3-induced apoptosis are significantly
      impaired in DR3-null mice. In contrast, both superantigen-induced negative
      selection and positive selection are normal. The pre-T-cell receptor-mediated
      checkpoint, which is dependent on TNFR signaling, is also unaffected in DR3
      deficient mice. These data reveal a nonredundant in vivo role for this TNF
      receptor family member in the removal of self-reactive T cells in the thymus.

PMID- 11313472
TI  - BSF binds specifically to the bicoid mRNA 3' untranslated region and contributes
      to stabilization of bicoid mRNA.
AB  - The early stages of Drosophila melanogaster development rely extensively on
      posttranscriptional forms of gene regulation. Deployment of the anterior body
      patterning morphogen, the Bicoid protein, requires both localization and
      translational regulation of the maternal bicoid mRNA. Here we provide evidence
      that the bicoid mRNA is also selectively stabilized during oogenesis. We identify
      and isolate a protein, BSF, that binds specifically to IV/V RNA, a minimal form
      of the bicoid mRNA 3' untranslated region that supports a normal program of mRNA
      localization during oogenesis. Mutations that disrupt the BSF binding site in
      IV/V RNA or substantially reduce the level of BSF protein lead to reduction in
      IV/V RNA levels, indicating a role for BSF in RNA stabilization. The BSF protein
      is novel and lacks all of the characterized RNA binding motifs. However, BSF does
      include multiple copies of the PPR motif, whose function is unknown but appears
      in other proteins with roles in RNA metabolism.

PMID- 11313473
TI  - Mobile self-splicing group I introns from the psbA gene of Chlamydomonas
      reinhardtii: highly efficient homing of an exogenous intron containing its own
      promoter.
AB  - Introns 2 and 4 of the psbA gene of Chlamydomonas reinhardtii chloroplasts
      (Cr.psbA2 and Cr.psbA4, respectively) contain large free-standing open reading
      frames (ORFs). We used transformation of an intronless-psbA strain (IL) to test
      whether these introns undergo homing. Each intron, plus short exon sequences, was
      cloned into a chloroplast expression vector in both orientations and then
      cotransformed into IL along with a spectinomycin resistance marker (16S rrn). For
      Cr.psbA2, the sense construct gave nearly 100% cointegration of the intron
      whereas the antisense construct gave 0%, consistent with homing. For Cr.psbA4,
      however, both orientations produced highly efficient cointegration of the intron.
      Efficient cointegration of Cr.psbA4 also occurred when the intron was introduced
      as a restriction fragment lacking any known promoter. Deletion of most of the
      ORF, however, abolished cointegration of the intron, consistent with homing. The
      Cr.psbA4 constructs also contained a 3-(3,4-dichlorophenyl)-1,1-dimethylurea
      resistance marker in exon 5, which was always present when the intron integrated,
      thus demonstrating exon coconversion. Remarkably, primary selection for this
      marker gave >100-fold more transformants (>10,000/microgram of DNA) than did the
      spectinomycin resistance marker. A trans homing assay was developed for Cr.psbA4;
      the ORF-minus intron integrated when the ORF was cotransformed on a separate
      plasmid. This assay was used to identify an intronic region between bp -88 and 
      194 (relative to the ORF) that stimulated homing and contained a possible
      bacterial (-10, -35)-type promoter. Primer extension analysis detected a
      transcript that could originate from this promoter. Thus, this mobile, self
      splicing intron also contains its own promoter for ORF expression. The
      implications of these results for horizontal intron transfer and organelle
      transformation are discussed.

PMID- 11313474
TI  - Interaction between hnRNPA1 and IkappaBalpha is required for maximal activation
      of NF-kappaB-dependent transcription.
AB  - Transcriptional activation of NF-kappaB is mediated by signal-induced
      phosphorylation and degradation of its inhibitor, IkappaBalpha. NF-kappaB
      activation induces a rapid resynthesis of IkappaBalpha which is responsible for
      postinduction repression of transcription. Following resynthesis, IkappaBalpha
      translocates to the nucleus, removes template bound NF-kappaB, and exports NF
      kappaB to the cytoplasm in a transcriptionally inactive form. Here we demonstrate
      that IkappaBalpha interacts directly with another nucleocytoplasmic shuttling
      protein, hnRNPA1, both in vivo and in vitro. This interaction requires one of the
      N-terminal RNA binding domains of hnRNPA1 and the C-terminal region of
      IkappaBalpha. Cells lacking hnRNPA1 are defective in NF-kappaB-dependent
      transcriptional activation, but the defect in these cells is complemented by
      ectopic expression of hnRNPA1. hnRNPA1 expression in these cells increased the
      amount of IkappaBalpha degradation, compared to that of the control cells, in
      response to activation by Epstein-Barr virus latent membrane protein 1. Thus in
      addition to regulating mRNA processing and transport, hnRNPA1 also contributes to
      the control of NF-kappaB-dependent transcription.

PMID- 11313475
TI  - A bipartite yeast SSRP1 analog comprised of Pob3 and Nhp6 proteins modulates
      transcription.
AB  - The FACT complex of vertebrate cells, comprising the Cdc68 (Spt16) and SSRP1
      proteins, facilitates transcription elongation on a nucleosomal template and
      modulates the elongation-inhibitory effects of the DSIF complex in vitro. Genetic
      findings show that the related yeast (Saccharomyces cerevisiae) complex, termed
      CP, also mediates transcription. The CP components Cdc68 and Pob3 closely
      resemble the FACT components, except that the C-terminal high-mobility group
      (HMG) box domain of SSRP1 is not found in the yeast homolog Pob3. We show here
      that Nhp6a and Nhp6b, small HMG box proteins with overlapping functions in yeast,
      associate with the CP complex and mediate CP-related genetic effects on
      transcription. Absence of the Nhp6 proteins causes severe impairment in
      combination with mutations impairing the Swi-Snf chromatin-remodeling complex and
      the DSIF (Spt4 plus Spt5) elongation regulator, and sensitizes cells to 6
      azauracil, characteristic of elongation effects. An artificial SSRP1-like
      protein, created by fusing the Pob3 and Nhp6a proteins, provides both Pob3 and
      Nhp6a functions for transcription, and competition experiments indicate that
      these functions are exerted in association with Cdc68. This particular Pob3-Nhp6a
      fusion protein was limited for certain Nhp6 activities, indicating that its Nhp6a
      function is compromised. These findings suggest that in yeast cells the Cdc68
      partners may be both Pob3 and Nhp6, functioning as a bipartite analog of the
      vertebrate SSRP1 protein.

PMID- 11313476
TI  - Human Taf(II)130 is a coactivator for NFATp.
AB  - NFATp is one member of a family of transcriptional activators that regulate the
      expression of cytokine genes. To study mechanisms of NFATp transcriptional
      activation, we established a reconstituted transcription system consisting of
      human components that is responsive to activation by full-length NFATp. The TATA
      associated factor (TAF(II)) subunits of the TFIID complex were required for NFATp
      mediated activation in this transcription system, since TATA-binding protein
      (TBP) alone was insufficient in supporting activated transcription. In vitro
      interaction assays revealed that human TAF(II)130 (hTAF(II)130) and its
      Drosophila melanogaster homolog dTAF(II)110 bound specifically and reproducibly
      to immobilized NFATp. Sequences contained in the C-terminal domain of NFATp
      (amino acids 688 to 921) were necessary and sufficient for hTAF(II)130 binding. A
      partial TFIID complex assembled from recombinant hTBP, hTAF(II)250, and
      hTAF(II)130 supported NFATp-activated transcription, demonstrating the ability of
      hTAF(II)130 to serve as a coactivator for NFATp in vitro. Overexpression of
      hTAF(II)130 in Cos-1 cells inhibited NFATp activation of a luciferase reporter.
      These studies demonstrate that hTAF(II)130 is a coactivator for NFATp and
      represent the first biochemical characterization of the mechanism of
      transcriptional activation by the NFAT family of activators.

PMID- 11313477
TI  - A novel form of transcriptional silencing by Sum1-1 requires Hst1 and the origin
      recognition complex.
AB  - In the yeast Saccharomyces cerevisiae, a and alpha mating-type information is
      stored in transcriptionally silenced cassettes called HML and HMR. Silencing of
      these loci, maintained by the formation of a specialized type of heterochromatin,
      requires trans-acting proteins and cis-acting elements. Proteins required for
      silencing include the Sir2 NAD(+)-dependent deacetylase, Sir3, and Sir4. Factors
      that bind to the cis elements at HMR and HML and that are important for silencing
      include the origin recognition complex (ORC). Mutations of any of these Sir
      proteins or combinations of cis elements result in loss of silencing. SUM1-1 was
      previously identified as a dominant mutation that restores silencing to HMR in
      the absence of either the Sir proteins or some of the cis elements. We have
      investigated the novel mechanism whereby Sum1-1 causes Sir-independent silencing
      at HMR and present the following findings: Sum1-1 requires the Sir2 homolog,
      Hst1, for silencing and most probably requires the NAD(+)-dependent deacetylase
      activity of this protein. Sum1-1 interacts strongly with ORC, and this strong
      interaction is dependent on HMR DNA. Furthermore, ORC is required for Sum1-1
      mediated silencing at HMR. These observations lead to a model for Sum1-1
      silencing of HMR in which Sum1-1 is recruited to HMR by binding to ORC. Sum1-1,
      in turn, recruits Hst1. Hst1 then deacetylates histones or other chromatin
      associated proteins to cause chromatin condensation and transcriptional
      silencing.

PMID- 11313478
TI  - Activated PAK4 regulates cell adhesion and anchorage-independent growth.
AB  - The serine/threonine kinase PAK4 is an effector molecule for the Rho GTPase
      Cdc42. PAK4 differs from other members of the PAK family in both sequence and
      function. Previously we have shown that an important function of this kinase is
      to mediate the induction of filopodia in response to activated Cdc42. Since
      previous characterization of PAK4 was carried out only with the wild-type kinase,
      we have generated a constitutively active mutant of the kinase to determine
      whether it has other functions. Expression of activated PAK4 in fibroblasts led
      to a transient induction of filopodia, which is consistent with its role as an
      effector for Cdc42. In addition, use of the activated mutant revealed a number of
      other important functions of this kinase that were not revealed by studying the
      wild-type kinase. For example, activated PAK4 led to the dissolution of stress
      fibers and loss of focal adhesions. Consequently, cells expressing activated PAK4
      had a defect in cell spreading onto fibronectin-coated surfaces. Most
      importantly, fibroblasts expressing activated PAK4 had a morphology that was
      characteristic of oncogenic transformation. These cells were anchorage
      independent and formed colonies in soft agar, similar to what has been observed
      previously in cells expressing activated Cdc42. Consistent with this, dominant
      negative PAK4 mutants inhibited focus formation by oncogenic Dbl, an exchange
      factor for Rho family GTPases. These results provide the first demonstration that
      a PAK family member can transform cells and indicate that PAK4 may play an
      essential role in oncogenic transformation by the GTPases. We propose that the
      morphological changes and changes in cell adhesion induced by PAK4 may play a
      direct role in oncogenic transformation by Rho family GTPases and their exchange
      factors.

PMID- 11313479
TI  - Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular
      distribution and activity of the forkhead transcription factor AFX.
AB  - AFX belongs to a subfamily of Forkhead transcription factors that are
      phosphorylated by protein kinase B (PKB), also known as Akt. Phosphorylation
      inhibits the transcriptional activity of AFX and changes the steady-state
      localization of the protein from the nucleus to the cytoplasm. Our goal was
      threefold: to identify the cellular compartment in which PKB phosphorylates AFX,
      to determine whether the nuclear localization of AFX plays a role in regulating
      its transcriptional activity, and to elucidate the mechanism by which
      phosphorylation alters the localization of AFX. We show that phosphorylation of
      AFX by PKB occurs in the nucleus. In addition, nuclear export mediated by the
      export receptor, Crm1, is required for the inhibition of AFX transcriptional
      activity. Both phosphorylated and unphosphorylated AFX, however, bind Crm1 and
      can be exported from the nucleus. These results suggest that export is
      unregulated and that phosphorylation by PKB is not required for the nuclear
      export of AFX. We show that AFX enters the nucleus by an active, Ran-dependent
      mechanism. Amino acids 180 to 221 of AFX comprise a nonclassical nuclear
      localization signal (NLS). S193, contained within this atypical NLS, is a PKB
      dependent phosphorylation site on AFX. Addition of a negative charge at S193 by
      mutating the residue to glutamate reduces nuclear accumulation. PKB-mediated
      phosphorylation of AFX, therefore, attenuates the import of the transcription
      factor, which shifts the localization of the protein from the nucleus to the
      cytoplasm and results in the inhibition of AFX transcriptional activity.

PMID- 11313480
TI  - Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic cells through
      inhibition of JAK2 kinase activity and induction of proteasome-mediated
      degradation.
AB  - TEL-JAK2 fusion proteins, which are a result of t(9;12)(p24;p13) translocations
      associated with human leukemia, activate Stat5 in vitro and in vivo and cause a
      myelo- and lymphoproliferative disease in a murine bone marrow transplant model.
      We report that Socs-1, a member of the SOCS family of endogenous inhibitors of
      JAKs and STATs, inhibits transformation of Ba/F3 cells by TEL-JAK2 but has no
      effect on Ba/F3 cells transformed by BCR-ABL, TEL-ABL, or TEL-platelet-derived
      growth factor receptor beta. TEL-JAK2, in addition to activating Stat5,
      associates with Shc and Grb2 and induces activation of Erk2, and expression of
      Socs-1 inhibits engagement of each of these signaling molecules. TEL-JAK2 kinase
      activity is inhibited by Socs-1, as assessed by in vitro kinase assays. In
      addition, Socs-1 induces proteasomal degradation of TEL-JAK2. Mutational analysis
      indicates that the SOCS box of Socs-1 is required for proteasomal degradation and
      for abrogation of growth of TEL-JAK2-transformed cells. Furthermore, murine bone
      marrow transplant assays demonstrate that expression of Socs-1 prolongs latency
      of TEL-JAK2-mediated disease in vivo. Collectively, these data indicate that Socs
      1 inhibits TEL-JAK2 in vitro and in vivo through inhibition of kinase activity
      and induction of TEL-JAK2 protein degradation.

PMID- 11313481
TI  - Role of DNA polymerase eta in the bypass of a (6-4) TT photoproduct.
AB  - UV light-induced DNA lesions block the normal replication machinery. Eukaryotic
      cells possess DNA polymerase eta (Poleta), which has the ability to replicate
      past a cis-syn thymine-thymine (TT) dimer efficiently and accurately, and
      mutations in human Poleta result in the cancer-prone syndrome, the variant form
      of xeroderma pigmentosum. Here, we test Poleta for its ability to bypass a (6-4)
      TT lesion which distorts the DNA helix to a much greater extent than a cis-syn TT
      dimer. Opposite the 3' T of a (6-4) TT photoproduct, both yeast and human Poleta
      preferentially insert a G residue, but they are unable to extend from the
      inserted nucleotide. DNA Polzeta, essential for UV induced mutagenesis,
      efficiently extends from the G residue inserted opposite the 3' T of the (6-4) TT
      lesion by Poleta, and Polzeta inserts the correct nucleotide A opposite the 5' T
      of the lesion. Thus, the efficient bypass of the (6-4) TT photoproduct is
      achieved by the combined action of Poleta and Polzeta, wherein Poleta inserts a
      nucleotide opposite the 3' T of the lesion and Polzeta extends from it. These
      biochemical observations are in concert with genetic studies in yeast indicating
      that mutations occur predominantly at the 3' T of the (6-4) TT photoproduct and
      that these mutations frequently exhibit a 3' T-->C change that would result from
      the insertion of a G opposite the 3' T of the (6-4) TT lesion.

PMID- 11313483
TI  - Coupling of mitotic chromosome tethering and replication competence in epstein
      barr virus-based plasmids.
AB  - The Epstein-Barr virus (EBV) replicates once per cell cycle and segregates with
      high efficiency yet does not encode the enzymes needed for DNA replication or the
      proteins required to contact mitotic spindles. The virus-encoded EBNA-1 (EBV
      nuclear antigen 1) and latent replication origin (oriP) are required for both
      replication and segregation. We developed a sensitive and specific fluorescent
      labeling strategy to analyze the interactions of both EBNA-1 with viral episomes
      and viral episomes with host chromosomes. This enabled investigation of the
      hypothesis that replication and chromosome tethering are linked through the EBNA
      1 protein. We show that deleting EBNA-1 or oriP disrupts mitotic chromosome
      tethering but removing the dyad symmetry element of oriP does not. Microscopic
      and biochemical approaches demonstrated that an EBNA-1 mutant lacking residues 16
      to 372 bound to oriP plasmids but did not support their mitotic chromosome
      association and that the mutant lost the ability of wild-type EBNA-1 to associate
      with interphase chromatin. Importantly, the transient-replication abilities of
      various mutant forms of EBV plasmids, including the mutant form with the EBNA-1
      internal deletion, correlated directly with their chromosome-tethering abilities.
      These data lead us to propose that EBNA-1 recruits oriP-containing plasmids into
      chromatin subdomains in interphase nuclei to both engage the host replication
      machinery and enable the plasmids to adhere to host chromosomes to increase their
      segregation efficiency.

PMID- 11313482
TI  - Localization of the Rsp5p ubiquitin-protein ligase at multiple sites within the
      endocytic pathway.
AB  - The Saccharomyces cerevisiae RSP5 gene encodes an essential HECT E3 ubiquitin
      protein ligase. Rsp5p contains an N-terminal C2 domain, three WW domains in the
      central portion of the molecule, and a C-terminal catalytic HECT domain. A
      diverse group of substrates of Rsp5p and vertebrate C2 WW-domain-containing HECT
      E3s have been identified, including both nuclear and membrane-associated
      proteins. We determined the intracellular localization of Rsp5p and the
      determinants necessary for localization, in order to better understand how Rsp5p
      activities are coordinated. Using both green fluorescent protein fusions to Rsp5p
      and immunogold electron microscopy, we found that Rsp5p was distributed in a
      punctate pattern at the plasma membrane, corresponding to membrane invaginations
      that are likely sites of endosome formation, as well as at perivacuolar sites.
      The latter appeared to correspond to endocytic intermediates, as these structures
      were not seen in a sla2/end4-1 mutant, and double-immunogold labeling
      demonstrated colocalization of Rsp5p with the endosomal markers Pep12p and
      Vps32p. The C2 domain was an important determinant of localization; however,
      mutations that disrupted HECT domain function also caused mislocalization of
      Rsp5p, indicating that enzymatic activity is linked to localization. Deletion of
      the C2 domain partially stabilized Fur4p, a protein previously shown to undergo
      Rsp5p- and ubiquitin-mediated endocytosis; however, Fur4p was still ubiquitinated
      at the plasma membrane when the C2 domain was deleted from the protein. Together,
      these results indicate that Rsp5p is located at multiple sites within the
      endocytic pathway and suggest that Rsp5p may function at multiple steps in the
      ubiquitin-mediated endocytosis pathway.

PMID- 11313484
TI  - Protein interactions of the MLL PHD fingers modulate MLL target gene regulation
      in human cells.
AB  - The PHD fingers of the human MLL and Drosophila trx proteins have strong amino
      acid sequence conservation but their function is unknown. We have determined that
      these fingers mediate homodimerization and binding of MLL to Cyp33, a nuclear
      cyclophilin. These two proteins interact in vitro and in vivo in mammalian cells
      and colocalize at specific nuclear subdomains. Overexpression of the Cyp33
      protein in leukemia cells results in altered expression of HOX genes that are
      targets for regulation by MLL. These alterations are suppressed by cyclosporine
      and are not observed in cell lines that express a mutant MLL protein without PHD
      fingers. These results suggest that binding of Cyp33 to MLL modulates its effects
      on the expression of target genes.

PMID- 11313485
TI  - Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in
      mice.
AB  - SNF5/INI1 is a component of the ATP-dependent chromatin remodeling enzyme family
      SWI/SNF. Germ line mutations of INI1 have been identified in children with brain
      and renal rhabdoid tumors, indicating that INI1 is a tumor suppressor. Here we
      report that disruption of Ini1 expression in mice results in early embryonic
      lethality. Ini1-null embryos die between 3.5 and 5.5 days postcoitum, and Ini1
      null blastocysts fail to hatch, form the trophectoderm, or expand the inner cell
      mass when cultured in vitro. Furthermore, we report that approximately 15% of
      Ini1-heterozygous mice present with tumors, mostly undifferentiated or poorly
      differentiated sarcomas. Tumor formation is associated with a loss of
      heterozygocity at the Ini1 locus, characterizing Ini1 as a tumor suppressor in
      mice. Thus, Ini1 is essential for embryo viability and for repression of
      oncogenesis in the adult organism.

PMID- 11313487
TI  - A quantum adiabatic evolution algorithm applied to random instances of an NP
      complete problem.
AB  - A quantum system will stay near its instantaneous ground state if the Hamiltonian
      that governs its evolution varies slowly enough. This quantum adiabatic behavior
      is the basis of a new class of algorithms for quantum computing. We tested one
      such algorithm by applying it to randomly generated hard instances of an NP
      complete problem. For the small examples that we could simulate, the quantum
      adiabatic algorithm worked well, providing evidence that quantum computers (if
      large ones can be built) may be able to outperform ordinary computers on hard
      sets of instances of NP-complete problems.

PMID- 11313486
TI  - Characterization of XIAP-deficient mice.
AB  - The inhibitor of apoptosis protein (IAP) family consists of a number of
      evolutionarily conserved proteins that function to inhibit programmed cell death.
      X-linked IAP (XIAP) was cloned due to its sequence homology with other family
      members and has previously been shown to prevent apoptosis by binding to active
      caspases 3, 7, and 9 in vitro. XIAP transcripts can be found in a variety of
      tissues, and the protein levels are regulated both transcriptionally and
      posttranscriptionally. To better understand the function of XIAP in normal cells,
      we generated mice deficient in XIAP through homologous gene targeting. The
      resulting mice were viable, and histopathological analysis did not reveal any
      differences between XIAP-deficient and wild-type mice. We were unable to detect
      any defects in induction of caspase-dependent or -independent apoptosis in cells
      from the gene-targeted mice. One change was observed in cells derived from XIAP
      deficient mice: the levels of c-IAP1 and c-IAP2 protein were increased. This
      suggests that there exists a compensatory mechanism that leads to upregulation of
      other family members when XIAP expression is lost. The changes in c-IAP1 and c
      IAP2 expression may provide functional compensation for loss of XIAP during
      development or in the induction of apoptosis.

PMID- 11313488
TI  - Self-assembly of subnanometer-diameter single-wall MoS2 nanotubes.
AB  - We report on the synthesis, structure, and self-assembly of single-wall
      subnanometer-diameter molybdenum disulfide tubes. The nanotubes are up to
      hundreds of micrometers long and display diverse self-assembly properties on
      different length scales, ranging from twisted bundles to regularly shaped "furry"
      forms. The bundles, which contain interstitial iodine, can be readily
      disassembled into individual molybdenum disulfide nanotubes. The synthesis was
      performed using a novel type of catalyzed transport reaction including C(60) as a
      growth promoter.

PMID- 11313489
TI  - Probing the structure of metal cluster-adsorbate systems with high-resolution
      infrared spectroscopy.
AB  - High-resolution infrared laser spectroscopy was used to obtain rotationally
      resolved infrared spectra of adsorbate-metal complexes. The method involves
      forming the bare metal clusters in helium nanodroplets and then adding a
      molecular adsorbate (HCN) and recording the infrared spectrum associated with the
      C-H stretching vibration. Rotationally resolved spectra were obtained for HCN
      Mg(n) (n = 1 to 4). The results suggest a qualitative change in the adsorbate
      metal cluster bonding with cluster size.

PMID- 11313490
TI  - Imaging of small-scale features on 433 Eros from NEAR: evidence for a complex
      regolith.
AB  - On 25 October 2000, the Near Earth Asteroid Rendevous (NEAR)-Shoemaker spacecraft
      executed a low-altitude flyover of asteroid 433 Eros, making it possible to image
      the surface at a resolution of about 1 meter per pixel. The images reveal an
      evolved surface distinguished by an abundance of ejecta blocks, a dearth of small
      craters, and smooth material infilling some topographic lows. The subdued
      appearance of craters of different diameters and the variety of blocks and
      different degrees of their burial suggest that ejecta from several impact events
      blanketed the region imaged at closest approach and led to the building up of a
      substantial and complex regolith consisting of fine materials and abundant meter
      sized blocks.

PMID- 11313491
TI  - Laser altimetry of small-scale features on 433 Eros from NEAR-Shoemaker.
AB  - During the Near Earth Asteroid Rendezvous (NEAR)-Shoemaker's low-altitude flyover
      of asteroid 433 Eros, observations by the NEAR Laser Rangefinder (NLR) have
      helped to characterize small-scale surface features. On scales from meters to
      hundreds of meters, the surface has a fractal structure with roughness dominated
      by blocks, structural features, and walls of small craters. This fractal
      structure suggests that a single process, possibly impacts, dominates surface
      morphology on these scales.

PMID- 11313492
TI  - Matriarchs as repositories of social knowledge in African elephants.
AB  - Despite widespread interest in the evolution of social intelligence, little is
      known about how wild animals acquire and store information about social
      companions or whether individuals possessing enhanced social knowledge derive
      biological fitness benefits. Using playback experiments on African elephants
      (Loxodonta africana), we demonstrated that the possession of enhanced
      discriminatory abilities by the oldest individual in a group can influence the
      social knowledge of the group as a whole. These superior abilities for social
      discrimination may result in higher per capita reproductive success for female
      groups led by older individuals. Our findings imply that the removal of older,
      more experienced individuals, which are often targets for hunters because of
      their large size, could have serious consequences for endangered populations of
      advanced social mammals such as elephants and whales.

PMID- 11313493
TI  - Fecundity-survival trade-offs and parental risk-taking in birds.
AB  - Life history theory predicts that parents should value their own survival over
      that of their offspring in species with a higher probability of adult survival
      and fewer offspring. We report that Southern Hemisphere birds have higher adult
      survival and smaller clutch sizes than Northern Hemisphere birds. We subsequently
      manipulated predation risk to adults versus offspring in 10 species that were
      paired between North and South America on the basis of phylogeny and ecology. As
      predicted, southern parents responded more strongly to reduce mortality risk to
      themselves even at a cost to their offspring, whereas northern parents responded
      more strongly to reduce risk to their offspring even at greater risk to
      themselves.

PMID- 11313494
TI  - Expanding the genetic code of Escherichia coli.
AB  - A unique transfer RNA (tRNA)/aminoacyl-tRNA synthetase pair has been generated
      that expands the number of genetically encoded amino acids in Escherichia coli.
      When introduced into E. coli, this pair leads to the in vivo incorporation of the
      synthetic amino acid O-methyl-l-tyrosine into protein in response to an amber
      nonsense codon. The fidelity of translation is greater than 99%, as determined by
      analysis of dihydrofolate reductase containing the unnatural amino acid. This
      approach should provide a general method for increasing the genetic repertoire of
      living cells to include a variety of amino acids with novel structural, chemical,
      and physical properties not found in the common 20 amino acids.

PMID- 11313495
TI  - Enlarging the amino acid set of Escherichia coli by infiltration of the valine
      coding pathway.
AB  - Aminoacyl transfer RNA (tRNA) synthetases establish the rules of the genetic code
      by catalyzing the aminoacylation of tRNAs. For some synthetases, accuracy depends
      critically on an editing function at a site distinct from the aminoacylation
      site. Mutants of Escherichia coli that incorrectly charge tRNA(Val) with cysteine
      were selected after random mutagenesis of the whole chromosome. All mutations
      obtained were located in the editing site of valyl-tRNA synthetase. More than 20%
      of the valine in cellular proteins from such an editing mutant organism could be
      replaced with the noncanonical aminobutyrate, sterically similar to cysteine.
      Thus, the editing function may have played a central role in restricting the
      genetic code to 20 amino acids. Disabling this editing function offers a powerful
      approach for diversifying the chemical composition of proteins and for emulating
      evolutionary stages of ambiguous translation.

PMID- 11313496
TI  - astray, a zebrafish roundabout homolog required for retinal axon guidance.
AB  - As growing retinotectal axons navigate from the eye to the tectum, they sense
      guidance molecules distributed along the optic pathway. Mutations in the
      zebrafish astray gene severely disrupt retinal axon guidance, causing anterior
      posterior pathfinding defects, excessive midline crossing, and defasciculation of
      the retinal projection. Eye transplantation experiments show that astray function
      is required in the eye. We identify astray as zebrafish robo2, a member of the
      Roundabout family of axon guidance receptors. Retinal ganglion cells express
      robo2 as they extend axons. Thus, robo2 is required for multiple axon guidance
      decisions during establishment of the vertebrate visual projection.

PMID- 11313497
TI  - Fast backprojections from the motion to the primary visual area necessary for
      visual awareness.
AB  - Much is known about the pathways from photoreceptors to higher visual areas in
      the brain. However, how we become aware of what we see or of having seen at all
      is a problem that has eluded neuroscience. Recordings from macaque V1 during
      deactivation of MT+/V5 and psychophysical studies of perceptual integration
      suggest that feedback from secondary visual areas to V1 is necessary for visual
      awareness. We used transcranial magnetic stimulation to probe the timing and
      function of feedback from human area MT+/V5 to V1 and found its action to be
      early and critical for awareness of visual motion.

PMID- 11313498
TI  - Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution.
AB  - Structures of a 10-subunit yeast RNA polymerase II have been derived from two
      crystal forms at 2.8 and 3.1 angstrom resolution. Comparison of the structures
      reveals a division of the polymerase into four mobile modules, including a clamp,
      shown previously to swing over the active center. In the 2.8 angstrom structure,
      the clamp is in an open state, allowing entry of straight promoter DNA for the
      initiation of transcription. Three loops extending from the clamp may play roles
      in RNA unwinding and DNA rewinding during transcription. A 2.8 angstrom
      difference Fourier map reveals two metal ions at the active site, one
      persistently bound and the other possibly exchangeable during RNA synthesis. The
      results also provide evidence for RNA exit in the vicinity of the carboxyl
      terminal repeat domain, coupling synthesis to RNA processing by enzymes bound to
      this domain.

PMID- 11313499
TI  - Structural basis of transcription: an RNA polymerase II elongation complex at 3.3
      A resolution.
AB  - The crystal structure of RNA polymerase II in the act of transcription was
      determined at 3.3 A resolution. Duplex DNA is seen entering the main cleft of the
      enzyme and unwinding before the active site. Nine base pairs of DNA-RNA hybrid
      extend from the active center at nearly right angles to the entering DNA, with
      the 3' end of the RNA in the nucleotide addition site. The 3' end is positioned
      above a pore, through which nucleotides may enter and through which RNA may be
      extruded during back-tracking. The 5'-most residue of the RNA is close to the
      point of entry to an exit groove. Changes in protein structure between the
      transcribing complex and free enzyme include closure of a clamp over the DNA and
      RNA and ordering of a series of "switches" at the base of the clamp to create a
      binding site complementary to the DNA-RNA hybrid. Protein-nucleic acid contacts
      help explain DNA and RNA strand separation, the specificity of RNA synthesis,
      "abortive cycling" during transcription initiation, and RNA and DNA translocation
      during transcription elongation.

PMID- 11313500
TI  - A silent slip event on the deeper Cascadia subduction interface.
AB  - Continuous Global Positioning System sites in southwestern British Columbia,
      Canada, and northwestern Washington state, USA, have been moving landward as a
      result of the locked state of the Cascadia subduction fault offshore. In the
      summer of 1999, a cluster of seven sites briefly reversed their direction of
      motion. No seismicity was associated with this event. The sudden displacements
      are best explained by approximately 2 centimeters of aseismic slip over a 50
      kilometer-by-300-kilometer area on the subduction interface downdip from the
      seismogenic zone, a rupture equivalent to an earthquake of moment magnitude 6.7.
      This provides evidence that slip of the hotter, plastic part of the subduction
      interface, and hence stress loading of the megathrust earthquake zone, can occur
      in discrete pulses.

PMID- 11313502
TI  - Birth attendants: one or two?

PMID- 11313503
TI  - Child rearing and positive deviance in the development of preschoolers: a
      microanalysis.
AB  - OBJECTIVE: To study the maternal child-rearing behaviors, parental attributes and
      socio-economic status of the family and to analyze their association with
      positive deviance in the developmental status of preschool children between 1-5
      years of age. DESIGN: Cross-sectional. SETTING: Rural community. METHODS: A total
      of 260 children and their mothers were evaluated. Weight and height-for-age
      indices were used to assess growth. ICMR Developmental Screening Test was used to
      assess psychosocial development. Bhatia's Performance Test was used to assess
      maternal intelligence. Narayan Rao's Rating Scale was used to assess socio
      economic status and a child-rearing interview schedule developed and pretested
      for the purpose of the study to assess maternal child-rearing practices and
      behaviors. RESULTS: Stepwise multiple regression with psychosocial development as
      dependent variable indicated significant associations between specific maternal
      behavioral categories and psychosocial development of 1-5 year old children.
      Children, whose mothers were responsive to their needs, were consistent in their
      interaction with them and were also emotionally stable during specific child
      rearing situations were those identified as "positive deviants" with regard to
      their development. Other factors, which were significantly associated with
      positive deviance in children, were paternal literacy and nuclear type of family.
      Significant differences were observed between genders. CONCLUSIONS: The data
      generated from the study could identify the important factors that were
      associated with "positive deviance" in the development of children. These factors
      can be useful components for parental counseling in clinical practice and as
      educational material in community programmes such as the ICDS and self-help
      groups at the village level.

PMID- 11313501
TI  - A GDP/GTP exchange factor involved in linking a spatial landmark to cell
      polarity.
AB  - In both animal and yeast cells, signaling pathways involving small guanosine
      triphosphatases (GTPases) regulate polarized organization of the actin
      cytoskeleton. In the budding yeast Saccharomyces cerevisiae, the Ras-like GTPase
      Bud1/Rsr1 and its guanosine 5'-diphosphate (GDP)/guanosine 5'-triphosphate (GTP)
      exchange factor Bud5 are involved in the selection of a specific site for growth,
      thus determining cell polarity. We found that Bud5 is localized at the cell
      division site and the presumptive bud site. Its localization is dependent on
      potential cellular landmarks, such as Bud3 and Axl2/Bud10 in haploid cells and
      Bud8 and Bud9 in diploid cells. Bud5 also physically interacts with Axl2/Bud10, a
      transmembrane glycoprotein, suggesting that a receptor-like transmembrane protein
      recruits a GDP/GTP exchange factor to connect an intrinsic spatial signal to
      oriented cell growth.

PMID- 11313504
TI  - Comparative efficiency of commercial and improvised spacer device in acute
      bronchial asthma.
AB  - OBJECTIVE: To compare the efficacy of a commercial spacer device versus an
      improvised spacer device in delivering aerosolized beta-2 agonist through metered
      dose inhaler in an acute exacerbation of bronchial asthma. DESIGN: Randomized
      controlled trial. SETTING: Urban tertiary care teaching hospital. METHODS: 60
      children between 1 to 12 years of age with acute asthma were prospectively
      enrolled and randomized into two groups. Detailed history, clinical evaluation
      and appropriate laboratory investigations were recorded on a pretested proforma.
      One group received inhaled salbutamol using metered dose inhaler via commercial
      spacer device (Group 1), while the other received it via improvised spacer device
      (Group II). The response was sequentially assessed after 20, 40 and 60 minutes of
      institution of therapy. RESULTS: The two groups were comparable with respect to
      various parameters at presentation (p > 0.05). All the outcome parameters showed
      a significant improvement with time in both groups (p < 0.05). There was no
      statistical difference between the response in the two groups (p< 0.05).
      CONCLUSION: Metered dose inhaler with improvised spacer device is equivalent in
      efficacy and a more cost effective alternative to metered dose inhaler with
      commercial spacer for administration of beta-2 agonist in acute asthma.

PMID- 11313505
TI  - Hepatitis B in India: a review of disease epidemiology.

PMID- 11313507
TI  - Research in office practice.

PMID- 11313506
TI  - Teicoplanin.

PMID- 11313508
TI  - Simplified intraosseous needle.

PMID- 11313509
TI  - Impact of breastfeeding on weight gain and incidence of diarrhea among low birth
      weight infants of an urban slum of Calcutta.

PMID- 11313510
TI  - Clinical and neurodevelopmental profile of young children with autism.

PMID- 11313511
TI  - Epileptic encephalopathies of early childhood.

PMID- 11313512
TI  - Dietary regimen for persistent diarrhea in infants under four months.

PMID- 11313513
TI  - Antitubercular drug formulations for children.

PMID- 11313514
TI  - Non-Hodgkins lymphoma in a child presenting as nephromegaly and acute renal
      failure.

PMID- 11313515
TI  - Acquired lobar emphysema--an unusual cause of respiratory distress.

PMID- 11313516
TI  - Ascariasis associated hemorrhagic pancreatitis.

PMID- 11313517
TI  - Levamisole induced ataxia.

PMID- 11313518
TI  - Castlemans's disease: an unusual presentation in cervical region.

PMID- 11313519
TI  - Staphylococcal scalded skin syndrome.

PMID- 11313520
TI  - Dose of varicella vaccine.

PMID- 11313522
TI  - Hepato-cerebral complications in ascariasis.

PMID- 11313523
TI  - Isolated menarche and multicystic ovaries in a 7 1/2 year girl with
      hypothyroidism.

PMID- 11313524
TI  - Delivery room management of neonates born through meconium stained amniotic
      fluid.

PMID- 11313526
TI  - More details on spectrum of Attention Deficit Hyperactivity Disorder.

PMID- 11313529
TI  - The last word.

PMID- 11313528
TI  - Foot-and-mouth disease--the vaccine.

PMID- 11313530
TI  - Toxoplasma gondii.

PMID- 11313532
TI  - Introducing danger.

PMID- 11313534
TI  - Sex in the littoral.

PMID- 11313535
TI  - Who needs countryside sports?
AB  - Countryside sports have never been more fiercely debated than they are today,
      though it is easy to get lost in the headlines. If conservation (at no cost to
      the taxpayer) and hunting are integrally linked, might we be shooting ourselves
      in the foot when we aim to eliminate countryside sports?

PMID- 11313536
TI  - HIV: vaccines out of Africa.
AB  - When HIV was first identified as the cause of AIDS in 1983, it was widely
      expected that a vaccine would be relatively straightforward to make. Why,
      eighteen years later, are we still waiting?

PMID- 11313537
TI  - Seeing rainbows.
AB  - Mammals generally have colour vision inferior to that of other vertebrates. This
      is partially redressed in primates, but the underlying mechanisms differ in Old
      World and New World primate groups. How has this occurred and what were the key
      events in the molecular evolution of primate colour vision?

PMID- 11313538
TI  - Letting the cat out of the bag.
AB  - The image of the cheetah sprinting gracefully across the African Serengeti in
      pursuit of its prey is one that we're all familiar with. Many people perceive the
      cheetah as an animal flawlessly adapted to its environment-the perfect predator.

PMID- 11313539
TI  - Flies in the face of adversity.
AB  - All organisms face attack from many natural enemies and all in turn have some
      means of defence. Can resistance evolve, and if it can, why doesn't it? Recent
      work on fruit flies and their parasitic wasps has shed light on these questions.

PMID- 11313540
TI  - Translating the message.
AB  - The "one gene = one protein" model for understanding the genome is well-known.
      But, as with most biological "rules", it has its exceptions. The viral family
      that brings polio, the common cold and foot-and-mouth disease translates its
      entire genome into one long "polyprotein". The study of this translation strategy
      is bringing to light new targets for fighting disease and new techniques for the
      biotech industry.

PMID- 11313541
TI  - Up on the roof with a "passion for pollen".
AB  - In spite of gale force winds and accompanying rain, monitoring pollen and spores
      in the rooftop airstream has its attractions, not least of which is the
      spectacular 360-degree panoramic view of Edinburgh and the surrounding
      countryside on a clear sunny morning.

PMID- 11313542
TI  - Watch out guinea pigs, here I come.
AB  - We live in an age of increasing emphasis of do-it-yourself, as a mere glance at
      the TV schedule will prove. Why not apply this same principle to your research?
      By becoming the guinea pig of your own experimentation you will be following a
      noble precedent--though maybe not a sane one!

PMID- 11313543
TI  - Alas, poor Darwin.
AB  - No, not a reflection on the environmental threat to the Galapagos. Rather, it is
      a reference to Darwin's own complaint, towards the end of his life, concerning
      those who misunderstood and misrepresented his theories.

PMID- 11313545
TI  - Redetermination of CaMn2O4.
AB  - The title compound, calcium dimanganese tetraoxide, CaMn(2)O(4), was synthesized
      hydrothermally and is made up of edge-sharing Mn(3+) distorted octahedral layers
      and eight-coordinate Ca(2+) centered polyhedral layers.

PMID- 11313546
TI  - (Li0.91Mn0.09)Mn2O4.
AB  - Lithium manganese oxide crystals with composition (Li(0.91)Mn(0.09))Mn(2)O(4)
      were synthesized by a flux method. The crystals have a structure closely related
      to that of the cubic spinel LiMn(2)O(4), but 9% of the lithium ions in the
      tetrahedral 4a site are substituted by Mn(2+) ions. This substitution lowers the
      average Mn oxidation state below 3.5+, resulting in a Jahn-Teller distortion of
      the MnO(6) octahedron.

PMID- 11313547
TI  - RbCu2VS4.
AB  - The reaction of Cu and V in a Rb(2)S(5) melt yields black crystals of rubidium
      dicopper vanadium tetrasulfide, RbCu(2)VS(4). The structure is comprised of
      [Cu(2)VS(4)](-) layers within the (010) plane which are separated by Rb(+)
      cations. The layers consist of a network of edge- and corner-sharing [VS(4)] and
      [CuS(4)] tetrahedra parallel to (010). The optical band gap was determined as
      1.45 eV.

PMID- 11313548
TI  - Rb4Mo21Se24 containing Mo12 and Mo15 clusters.
AB  - Rubidium molybdenum selenide, Rb(4)Mo(21)Se(24), crystallizes in the trigonal
      space group R-3. Its crystal structure consists of a mixture of Mo(12)Se(14)Se(6)
      and Mo(15)Se(17)Se(6) cluster units in a 1:2 ratio. Both units are interconnected
      through Mo-Se bonds. The Rb(+) cations occupy large voids between the different
      cluster units.

PMID- 11313549
TI  - Sr3ZnPtO6 and Sr3CdPtO6.
AB  - The flux synthesis of single crystals of the isostructural compounds tristrontium
      zinc platinum hexaoxide, Sr(3)ZnPtO(6), and tristrontium cadmium platinum
      hexaoxide, Sr(3)CdPtO(6), is reported. The compounds adopt the pseudo-one
      dimensional rhombohedral K(4)CdCl(6) structure type, and feature chains of face
      shared distorted ZnO(6) or CdO(6) trigonal prisms and PtO(6) octahedra,
      surrounded by columns of Sr(2+) ions. All transition metals are located on the
      threefold axis of symmetry, while the Sr(2+) cations lie on twofold axes.

PMID- 11313550
TI  - Barium oxoaluminate hydride.
AB  - The crystal structure of Ba(3)(AlO(4))H is isotypic with Ba(3)SiS(5) and contains
      AlO(4)(5-) and H(-) anions. The hydride and oxide anions are coordinated by six
      Ba and five Ba/one Al atoms in an octahedral geometry. The hydrogen content was
      examined by MAS-NMR experiments of the deuterated compound.

PMID- 11313551
TI  - Tetragonal SmBa2Cu3O7-x [x = 0.74(4)].
AB  - Crystals of the title compound, samarium barium copper oxide, were prepared by a
      modified top-seeded solution-growth method. The crystals thus prepared showed no
      superconductivity down to 4.2 K. A careful examination showed that the structure
      closely resembles that of tetragonal YBCO, and there is no atom mixing at the Ba
      or other sites, within experimental accuracy. A bond-valence-sum calculation at
      the Ba site also indicated the absence of Sm. Each site is fully occupied by a
      single atom, except for the oxygen site in the basal plane of the CuO(6)
      octahedron. The occupancy of this oxygen site is significantly reduced [0.13
      (2)], as is commonly observed in the 123 system. The atomic displacement
      parameters of the atoms in the CuO(2) plane, as well as of the Sm atom, are very
      small, indicating that two equivalent CuO(2) planes tightly sandwich the Sm atom.

PMID- 11313552
TI  - K5.76Ga5.76Si10.24O32.3.4H2O, a gallosilicate with the zeolite gismondine
      topology.
AB  - The title compound, K-GaSi-GIS, potassium gallium silicon oxide hydrate, was
      synthesized hydrothermally and its crystal structure was determined from data
      collected on a single crystal of dimensions 10 x 10 x 8 microm at a synchrotron X
      ray source. The compound, which has the aluminosilicate (AlSi) zeolite gismondine
      (GIS) topology, Ca(4)[Al(8)Si(8)O(32)].16H(2)O, crystallizes in the tetragonal
      space group I4(1)/a. A disordered distribution of the framework Si/Ga sites leads
      to higher symmetry of the GIS-type network compared with the usual monoclinic
      symmetry in AlSi-GIS. Framework Ga substitution for Al in AlSi-GIS leads to
      substantial distortion of the crankshaft chains, reducing the effective pore
      dimensions and suggesting the possibility of pore-dimension control via partial
      framework-cation substitution.

PMID- 11313553
TI  - Zinc cyanamide, Zn(CN2).
AB  - Single crystals of the title compound have been grown by annealing
      microcrystalline zinc cyanamide at 843 K in silver crucibles. Zn(CN(2))
      crystallizes as colourless prisms. The crystal structure is composed of corner
      linked ZnN(4/2) tetrahedra. Carbon and nitrogen form (CN(2))(2-) dumb-bells with
      the C atom on a twofold axis. Nitrogen is approximately trigonally planar,
      coordinated by two Zn atoms and one C atom.

PMID- 11313554
TI  - Bis(2,2-bipyridine-N,N')tetra-mu-chloro-tetracopper(I).
AB  - A novel centrosymmetric chair-like dimer, bis(2,2'-bipyridine)
      1kappa(2)N,N';3kappa(2)N,N'-tetra-mu-chloro
      1:2kappa(2)Cl;2:3kappa(2)Cl;3:4kappa(2)Cl;1:4kappa(2)Cl-tetracopper(I),
      [Cu(4)Cl(4)(C(10)H(8)N(2))(2)], has been solvothermally synthesized and
      structurally characterized. The complex self-assembles into a three-dimensional
      network via C-H.Cl hydrogen bonds, pi-pi stacking and weak Cu.Cl electrostatic
      interactions.

PMID- 11313555
TI  - Dicarbonyldi-mu-chloro-cis,cis-eta4-1,5-cyclooctadienedirhodium(I).
AB  - The title compound, dicarbonyl-1kappa(2)C-di-mu-chloro-1:2kappa(4)Cl-[cis,cis
      2(eta(4))-1,5-cyclooctadiene]dirhodium(I), [Rh(2)Cl(2)(C(8)H(12))(CO)(2)],
      consists of a dichloro-bridged dimer of rhodium, with a non-bonded Rh.Rh distance
      of 3.284 (2) A. One Rh atom is coordinated to two carbonyl ligands, while the
      other Rh atom is coordinated to the cyclooctadiene moiety.

PMID- 11313556
TI  - Dichloro(2,2'-diamino-4,4'-bi-1,3-thiazole-N3,N3')copper(II).
AB  - The title complex, [CuCl(2)(C(6)H(6)N(4)S(2))], has a flattened tetrahedral
      coordination. The Cu(II) atom is located on a twofold rotation axis and is
      coordinated by two N atoms from a chelating 2,2'-diamino-4,4'-bi-1,3-thiazole
      ligand and by two Cl atoms. Intramolecular hydrogen bonding exists between the
      amino groups of the 2,2'-diamino-4,4'-bi-1,3-thiazole ligand and the Cl atoms.
      The intermolecular separation of 3.425 (1) A between parallel bithiazole rings
      suggests there is a pi-pi interaction between them.

PMID- 11313557
TI  - [2-(Imidazol-4-yl)ethylamine]-([2-(imidazol-4-yl)ethyl][(1-methyl-imidazol-2
      yl)methyl]amine)copper(II) diperchlorate.
AB  - In the title mononuclear complex, [Cu(C(5)H(9)N(3))(C(10)H(15)N(5))](ClO(4))(2),
      the Cu(II) centre is surrounded by two N-donor ligands, which impose a square
      pyramidal environment on the metal. The new tridentate ligand [2-(imidazol-4
      yl)ethyl][(1-methylimidazol-2-yl)methyl]amine (HISMIMA) lies in the basal plane,
      while the histamine ligand occupies the apical and one of the basal positions
      around the Cu(II) ion.

PMID- 11313558
TI  - Trans-dioxocyclam (1,4,8,11-tetraazacyclotetradecane-2,9-dione) dihydrate and its
      NiII complex.
AB  - The crystal structures are reported of trans-dioxocyclam dihydrate,
      C(10)H(20)N(4)O(2).2H(2)O, a structural isomer of the well known cis-dioxocyclam,
      and of its novel Ni complex, (1,4,8,11-tetraazacyclotetradecane-2,9-dionato
      kappa(4)N)nickel(II) dihydrate, [Ni(C(10)H(18)N(4)O(2))].2H(2)O, the first
      example of a transition metal complex of this ligand. Both molecules lie on
      crystallographic centres of inversion. The free ligand has two of its N atoms
      turned outwards from the ring and hydrogen bonded to water molecules. A major
      conformational change takes place in the complex in which the ligand binds in a
      trans tetradentate fashion, as suggested by the electronic spectrum. The
      nickel(II) ion is low spin, although the electronic spectrum of the complex in
      water indicates an equilibrium mixture of low-spin and high-spin species. The
      irreversible electrochemical oxidation of [NiL(1)] (L(1) is deprotonated trans
      dioxocyclam, C(10)H(18)N(4)O(2)) in water occurs at a potential of 0.964 V
      [versus SHE (standard hydrogen electrode)], which is very similar to that for the
      Ni-cis-dioxocyclam complex.

PMID- 11313559
TI  - Bis(2,2'-bipyridine)(dicyanamido)copper(II) tetrafluoroborate.
AB  - In the title compound, [Cu(C(2)N(3))(C(10)H(8)N(2))(2)]BF(4), the Cu(II) atom
      shows distorted trigonal-bipyramidal geometry, with the dicyanamido ligand in the
      equatorial plane. The two out-of-plane Cu-N bond lengths to bipyridine are 2.006
      (3) and 1.998 (3) A, whereas the in-plane Cu-N distances are 2.142 (3) and 2.043
      (3) A to the bipyridine, and 2.015 (3) A to the dicyanamide.

PMID- 11313560
TI  - (N-[2-(eta[5]cyclopentadienyl)ethyl]-4-toluenesulfonamido-N,O)(tetrahydrofuran
      O)bis(trifluoromethanesulfonato-O)titanium(II).
AB  - The title compound, [Ti(CF(3)O(3)S)(2)(C(14)H(15)NO(2)S)(C(4)H(8)O)], contains a
      unique ligand system in which the Ti ion is bound to the N and O atoms of a 2-p
      toluenesulfonamide ligand, which is linked by an ethyl group to a coordinated
      cyclopentadiene moiety. The distorted octahedral geometry about the Ti ion is
      completed by two trifluoromethanesulfonate ligands and a tetrahydrofuran
      molecule. Comparison with related compounds shows that both the Ti-N and Ti-O
      bonds of the sulfonamide, although longer than normal values, indicate
      significant bonding interactions.

PMID- 11313561
TI  - Bis(mu-N-[2-(eta[5]-cyclopentadienyl)-ethyl]-4-toluenesulfonamido-N,O:O')
      bis[bis(trifluoromethanesulfonato-O)-titanium(II)]bis(dichloromethane) solvate.
AB  - The title compound, [Ti(2)(CF(3)O(3)S)(4)(C(14)H(15)NO(2)S)(2)].2CH(2)Cl(2),
      consists of unique centrosymmetric dimers, with an eight-membered ring derived
      from the monomer subunits by formation of two Ti-(N,O)-S-O head-to-tail sequences
      around a crystallographic inversion centre, and two ordered dichloromethane
      solvate molecules. The Ti ion has distorted octahedral coordination, through the
      N atom and one O atom of one p-toluenesulfonamido group linked by an ethyl group
      to the bound cyclopentadiene moiety, one O atom from the other p
      toluenesulfonamido group and two singly bound trifluoromethanesulfonates moieties
      which are coordinated in pseudo-cis positions. Both Ti-O(sulfonamido) bond
      lengths [2.149 (3) and 2.388 (3) A] are considered bonding interactions.

PMID- 11313562
TI  - Trans-[N,N'-Bis(salicydene)cyclohexane-1,2-diaminato]nickel(II)-chloroform (1/1).
AB  - In the title complex, trans-(2,2'-[cyclohexane-1,2
      diylbis(nitrilomethylidyne)]diphenolato-kappa(4)O,N,N',O')nickel(II)-chloroform
      (1/1), [Ni(C(20)H(20)N(2)O(2))].CHCl(3), the Ni atom has a square-planar
      geometry, slightly tetrahedrally distorted. The Ni-N and Ni-O bonding distances
      are within the expected ranges for Ni-Schiff base derivatives. The diimine bridge
      has a gauche conformation with the cyclohexyl ring almost coplanar with the
      NiN(2)O(2) plane. The complex molecules pack in dimers with an Ni.Ni distance of
      3.59 (1) A and form a three-dimensional structure displaying a herring-bone
      configuration. Channels are occupied by solvent molecules, which are involved in
      C-H.O hydrogen bonds with the ligand O atoms.

PMID- 11313563
TI  - (2,6-Bis[(dimethylamino)methyl]-phenyl-N(2),C(1),N(6))diphenyltin(II) bromide
      monohydrate.
AB  - In the title compound, [Sn(C(6)H(5))(2)(C(12)H(19)N(2))]Br.H(2)O, the Sn(IV) atom
      lies on a twofold axis and is coordinated by a C and two N atoms from the 2,6
      bis[(dimethylamino)methyl]phenyl ligand in a tridentate fashion and by two phenyl
      groups. The resulting geometry is intermediate between square pyramidal and
      trigonal bipyramidal, with three C atoms in equatorial and the two N atoms in
      axial positions. The main deformation from ideal trigonal-bipyramidal geometry is
      seen for the N-Sn-N angle [152.18 (7) degrees]. The Br(-) anion and the water
      solvate molecule are on an inversion centre and twofold axis, respectively. They
      form an infinite chain of Br.H-O-H.Br hydrogen bonds [Br.O 3.529 (2) A] without
      contributing to the primary coordination sphere of the Sn atom.

PMID- 11313564
TI  - (Bis[2-(2-oxido-1-naphthylmethylideneamino)phenyl]disulfide)chloroiron(III).
AB  - The crystal structure of the title compound, (bis[2-(2-oxido-2
      naphthylideneamino)phenyl] disulfide-kappa(5)O,N,S,N',O')chloroiron(III),
      [FeCl(C(34)H(22)N(2)O(2)S(2))], has been determined. The structure consists of
      monomeric iron(III) complexes with distorted octahedral coordination. The
      disulfide functions as a pentadentate ligand and the Fe(III) atom is coordinated
      through two N, two O and one S atom, and one chloride ion. The distance between
      the second S atom and the Fe(III) atom is a non-bonding 3.8473 (14) A.

PMID- 11313565
TI  - Poly[copper(I)-mu-bromo-mu-2,3-dimethylpyrazine-N:N'].
AB  - In the structure of the title compound, [CuBr(C(6)H(8)N(2))](n), each Cu(2+)
      cation is surrounded by two 2,3-dimethylpyrazine ligands and two Br(-) anions in
      a distorted tetrahedral arrangement. The Cu(2+) cations and Br(-) anions form
      (Cu(2)Br(2))(2) rhomboid dimers located around a centre of inversion. The 2,3
      dimethylpyrazine ligands connect the Cu(2+) cations in the dimers into sheets
      parallel to (010).

PMID- 11313566
TI  - 2,5-O-methylene-D-mannitol: two polymorphs and the NaI complex.
AB  - Two polymorphs of the title compound, (4R,5R,6R,7R)-4,7-bis(hydroxymethyl)-1,3
      dioxepane-5,6-diol, C(7)H(14)O(6), both have Z' = 2 at 100 K, and differ in their
      hydrogen-bonding patterns. The sodium iodide complex, NaI.C(7)H(14)O(6), is
      isomorphous with the NaCl complex, and has the mannitol, cation and anion all
      lying on twofold axes. The dioxepane rings of all three molecules are in the
      twist-chair conformation.

PMID- 11313567
TI  - Poly[[[1,2-mu)-benzene]silver(I)-mu-trifluoromethanesulfonate-O;O';O":O"].
AB  - The title compound, [Ag(CF(3)O(3)S)(C(6)H(6))], has been synthesized and
      characterized by low-temperature single-crystal X-ray diffraction. The complex is
      polymeric, with a network of trifluoromethanesulfonate anions bridging the silver
      cations. The terminal planar benzene ligand is asymmetrically eta(2)-coordinated
      to the Ag.

PMID- 11313568
TI  - Pentacarbonyl(4-phenylpyridine)tungsten(0) and pentacarbonyl(2
      phenylpyridine)chromium(0).
AB  - In pentacarbonyl(4-phenylpyridine)tungsten(0), [W(C(11)H(9)N)(CO)(5)], the
      molecules have mm site symmetry and the pyridine ligand, with m symmetry, is
      completely planar. In pentacarbonyl(2-phenylpyridine)chromium(0),
      [Cr(C(11)H(9)N)(CO)(5)], the molecules are in general positions and the phenyl
      and pyridine rings of the ligand are twisted by 67.7 (3) degrees with respect to
      one another by rotation about the C-C bond joining them. In both compounds, the
      axial M-C(carbonyl) bond trans to the M-N(ligand) bond is significantly shorter
      than the equatorial M-C(carbonyl) bonds.

PMID- 11313569
TI  - Aminoguanidinium(2+) aminoguanidinium(1+) hexachloroantimonate(III) at 295 and 92
      K.
AB  - The crystal and molecular structure of the title compound,
      (CH(7)N(4))(CH(8)N(4))[SbCl(6)], has been determined at 295 and 92 K. It is
      composed of isolated [SbCl(6)](3-) octahedra and aminoguanidinium mono- and
      dications. One of four of the crystallographically inequivalent aminoguanidinium
      cations is disordered at both temperatures. Two crystallographically inequivalent
      [SbCl(6)](3-) octahedra were found to possess three significantly longer Sb-Cl
      bonds than three other octahedra. The shorter bonds are in the range 2.456 (2)
      2.577 (2) A, whereas the longer ones are between 2.705 (2) and 2.931 (2) A. Each
      short Sb-Cl bond is located trans to a long bond. It is argued that this
      deformation is caused by N-H.Cl hydrogen bonds.

PMID- 11313570
TI  - An ion pair uniting a gadolinium(III)-Schiff base complex and uranyl
      tetrachloride.
AB  - The Schiff base N-(tert-butyl)-3-methoxysalicylaldimine (LH) forms a complex with
      gadolinium(III) chloride, [GdCl(2)(LH)(2)(C(5)H(5)N)(2)](+), in which the two O
      atoms of each ligand are coordinated (the phenolic O atom being deprotonated) and
      the imine N atom is protonated and involved in a hydrogen bond with the phenoxide
      group. This complex crystallizes as an ion pair with uranyl tetrachloride, i.e.
      bis(bis[2-(tert-butyliminiomethyl)-6-methoxyphenolato-O,O']dichlorobis(pyridine
      N)gadolinium(III)) tetrachlorodioxouranium(VI) tetrapyridine solvate
      [GdCl(2)(C(12)H(17)NO(2))(2)(C(5)H(5)N)(2)](2)[UCl(4)O(2)].4C(5)H(5)N. The U atom
      of the UCl(4)O(2) anion lies on an inversion centre.

PMID- 11313571
TI  - Trans-(DL-isoleucinato-N,O)[tris(2-aminoethyl)amine
      kappa(4)N]cobalt(III)diperchlorate..
AB  - The racemic title compound, trans-[N,N-bis(2-aminoethyl)-1,2-ethanediamine
      kappa(4)N](DL-isoleucinato-N,O)cobalt(III) diperchlorate,
      [Co(C(6)H(18)N(4))(C(6)H(12)NO(2))](ClO(4))(2), crystallizes in the
      enantiomorphous space group P2(1)2(1)2(1) with Z = 12 (Z' = 3). Each of the three
      cations in the asymmetric unit represents a different chirality of the isoleucine
      ligand; two of them are R (or D) and the third is the S (or L) enantiomer. The
      mixture crystallizes in a so-called unbalanced crystallization, in which the
      cations adopt a chiral array of composition RRS or SSR, depending on the crystal
      selected for data collection.

PMID- 11313572
TI  - Sodium 4-(2-pyridinyldiazenyl)resorcinolate monohydrate and ammonium 2,4-dinitro
      1-naphthalenolate from powder diffraction data.
AB  - The crystal structures of two dyestuffs, Na(+).C(11)H(8)N(3)O(2)(-).H(2)O, (I),
      and NH(4)(+).C(10)H(5)N(2)O(5)(-), (II), were determined from X-ray powder
      diffraction data. In both structures, translationally related anions form stacks,
      and cations fill interstack channels. A comparison of the diffuse reflectance
      spectra of crystalline (I) and (II) with the absorption spectra of their aqueous
      solutions demonstrates that the geometry of their anions does not change
      significantly upon transfer from the crystalline to the solution state.

PMID- 11313573
TI  - A uniform and one-dimensional stacking of 2,5-dichlorotetracyanoquinodimethanide
      molecules in the tetramethylarsonium salt.
AB  - In the tetramethylarsonium salt of 2,5-dichloro-7,7,8,8
      tetracyanoquinodimethanide [systematic name: tetramethylarsonium 2,2'-(2,5
      dichlorocyclohexa-2,5-diene-1,4-diylidene)bis(propanedinitrile)],
      C(4)H(12)As(+).C(12)H(2)Cl(2)N(4)(-) or [As(CH(3))(4)](C(12)H(2)Cl(2)N(4)), the
      cation lies disordered about a twofold axis and the radical ion lies about an
      inversion center forming a uniform [interplanar distance 3.35 (2) A] and one
      dimensional stacking without any slip. The electrical conductivity of the single
      crystal at room temperature was less than 10(-9) S cm(-1), and the temperature
      dependence of paramagnetic susceptibility obeyed a one-dimensional
      antiferromagnetic Heisenberg model with a spin-exchange integral of 83 K in the
      temperature range 1.8-320.0 K.

PMID- 11313574
TI  - Ferroelastic n-heptylammonium dihydrogenarsenate.
AB  - n-Heptylammonium dihydrogenarsenate, (C(7)H(18)N)[As(O)(2)(OH)(2)] (C7ADA), is
      ferroelastic at room temperature and isostructural with n-heptylammonium
      dihydrogenphosphate (C7ADP). In contrast to the other known n-alkylammonium
      dihydrogenphosphates (CnADP) and dihydrogenarsenates (CnADA), two independent
      anions in the present structure are substantially disordered ( approximately 88
      and approximately 12%, respectively). There are strong hydrogen bonds between the
      dihydrogenarsenates themselves, and moderate hydrogen bonds between the
      dihydrogenarsenates and the n-alkylammonium groups. The hydrogen-bond distances
      correspond well to those observed in the dihydrogenphosphates. There are two H
      atoms in the structure which are involved in asymmetric hydrogen bonds between
      respective oxygen pairs. These H atoms jump from the donor to the acceptor O
      atoms during ferroelastic switching.

PMID- 11313575
TI  - Superimposed saddle and ruffled distortions of the porphyrin in iodo(pyridine
      N)(5,10,15,20-tetraphenylporphyrinato-kappa(4)N)rhodium(III) toluene solvate.
AB  - In the title compound, [RhI(C(44)H(28)N(4))(C(5)H(5)N)].C(7)H(8), the porphyrin
      ring experiences significant distortion from planarity (a saddle conformation
      with a superimposed ruffling), as a result of steric interactions with the 2,6-H
      atoms of the axial pyridine ligand. This also leads to a slight lengthening of
      the Rh-pyridine bond [Rh-N 2.102 (7) A] relative to those seen in other pyridine
      adducts of six-coordinate Rh(III). The metric parameters of the porphyrin core
      are comparable with those of related metalloporphyrin derivatives. No significant
      intermolecular interactions are observed between the metalloporphyrin and
      disordered solvate species.

PMID- 11313576
TI  - Diiodo(3,4,5,6-tetrahydropyrimidinium-2-thiolato-S)mercury(II).
AB  - The reaction of 3,4,5,6-tetrahydropyrimidine-2-thione (H(4)pymtH) with
      mercury(II) iodide in methanol in a 1:1 molar ratio resulted in the formation of
      single crystals of the title compound, [Hg(C(4)H(8)N(2)S)I(2)]. The Hg atom is
      coordinated by one S atom from H(4)pymtH at 2.456 (2) A and by two I atoms at
      distances of 2.6872 (7) and 2.7044 (6) A, and has a characteristic deformed
      trigonal coordination geometry. The molecule has crystallographic m symmetry but
      the Hg atom is disordered above and below the mirror plane.

PMID- 11313577
TI  - 4-Ethynyl-1,2-methylenedioxybenzene at 150 K.
AB  - The title compound, C(9)H(6)O(2), contains two moderate C-H.O hydrogen bonds.
      That involving the terminal alkyne gives rise to chains along the b axis. The
      other hydrogen bond occurs over a centre of symmetry, leading to dimers. The
      combination of the two interactions gives rise to rings, each comprising six
      molecules, which are part of infinite sheets in the bc plane.

PMID- 11313578
TI  - 4-Methylcarbazole-3-carboxylic acid.
AB  - The title compound, C(14)H(11)NO(2), consists of a carbazole skeleton with
      carboxylic acid and methyl groups at positions 3 and 4, respectively. Molecules
      are linked about inversion centres by O-H.O hydrogen bonds [O.O 2.620 (3) A] to
      form centrosymmetric dimers.

PMID- 11313579
TI  - Conformation of cationic N,N-dimethylglycine in dimethylglycinium
      trifluoroacetate.
AB  - In the title compound, C(4)H(10)NO(2)(+).C(2)F(3)O(2)(-), the main N-C-COOH
      skeleton of the protonated amino acid is nearly planar. The C=O/C-N and C=O/O-H
      bonds are syn and the two methyl groups are gauche to the methylene H atoms. The
      conformation of the cation in the crystal is compared to that given by ab initio
      calculations (Hartree-Fock, self-consistent field molecular-orbital theory). The
      trifluoroacetate anion has the typical staggered conformation with usual bond
      distances and angles. The cation and anion form dimers through a strong O-H.O
      hydrogen bond which are further interconnected in infinite zigzag chains running
      parallel to the a axis by N-H.O bonds. Weaker C-H.O interactions involving the
      methyl groups and the carboxy O atoms of the cation occur between the chains.

PMID- 11313580
TI  - N-[tris(hydroxymethyl)methyl]glycine(tricine).
AB  - The title compound, C(6)H(13)NO(5), adopts a zwitterionic form where the
      carboxylic acid H atom is transferred to the amino group. The methyl-glycine
      backbone is planar. The tris(hydroxymethyl)methyl group is rotated as a rigid
      group around the amino-methyl bond by 22 (1) degrees and the carboxylic acid
      plane is rotated by 19.76 (12) degrees from the plane of the main skeleton. Apart
      from their H atoms, the three hydroxymethyl groups adopt a propeller-like
      conformation around the amino-methyl bond, close to C(3) symmetry.

PMID- 11313581
TI  - L-prolinium tartrate.
AB  - In the title salt, C(5)H(10)NO(2)(+).C(4)H(5)O(6)(-), proline exists as a cation
      and the tartaric acid as a semi-tartrate anion. The semi-tartrate ions form
      hydrogen-bonded strings along the c axis. These strings are interconnected
      through the proline molecules, forming a layered network parallel to the bc
      plane. The proline molecules, however, do not directly interact among themselves,
      except for a weak C-H.O hydrogen bond.

PMID- 11313582
TI  - 4-Ethoxycarbonyl-3-hydroxy-3-phenylcyclohexanone.
AB  - The title compound, ethyl 2-hydroxy-4-oxo-2-phenylcyclohexanecarboxylate,
      C(15)H(18)O(4), was obtained by a Michael-Aldol condensation and has the
      cyclohexanone in a chair conformation. The attached hydroxy, ethoxycarbonyl and
      phenyl groups are disposed in beta-axial, beta-equatorial and alpha-equatorial
      configurations, respectively. An intermolecular hydrogen bond, with an O.O
      distance of 2.874 (2) A, links the OH group and the ring carbonyl. Weak
      intermolecular C-H.O=C (ester and ketone), O-H.O=C (ketone) and C-H.OH hydrogen
      bonds exist.

PMID- 11313583
TI  - 9-(1-Acetoxyethylidene)fluorene ("diacetylfluorene"), a by-product from the
      acetylation of 9-fluorenyllithium.
AB  - Treatment of 9-fluorenyllithium with acetyl chloride produces 9-acetylfluorene,
      (I), and several by-products, among which is "diacetylfluorene", now
      characterized definitively as 9-(1-acetoxyethylidene)fluorene [IUPAC name: (1
      fluoren-9-ylidene)ethyl acetate], (II), C(17)H(14)O(2), derived from acetylation
      of initially formed (I). Various parameters disclose substantial structural
      distortion within (II) emanating from A((1,3)) strain associated with the 9
      (acetoxyethylidenyl)fluorene system.

PMID- 11313584
TI  - A comparison of 2,7-dihydro-2,2,7,7-tetramethyl-3,6-diphenyl-1,4,5-thiadiazepine
      and the corresponding 1,1-dioxide.
AB  - The structures of the highly substituted title heterocycles, C(20)H(22)N(2)S and
      C(20)H(22)N(2)O(2)S, have been determined at 123 (1) K. Both molecules possess
      exact C(2) symmetry and the seven-membered rings have very similar twist-boat
      conformations. The magnitudes of the C-S-C bond angles, 107.13 (6) and 108.27 (7)
      degrees, respectively, are influenced significantly by the four substituent
      methyl groups on the seven-membered rings.

PMID- 11313585
TI  - 3-(1-Hydroxyethylidene)-1-phenylpyrrolidine-2,4-dione.
AB  - Analysis of C(12)H(11)NO(3) revealed a coplanar N-substituted phenyl group on a
      pyrrolidine ring with two keto moieties and a hydroxyethylidene functionality.
      The hydroxy group forms part of a hydrogen-bonding network characterized by a
      short intramolecular H.O distance of 1.81 (3) A, and a longer intermolecular
      interaction with an H.O distance of 2.38 (3) A. Both keto groups form additional
      intra- and intermolecular C-H.O contacts with H.O distances ranging from 2.26 to
      2.41 A.

PMID- 11313586
TI  - Triclinic polymorph of sulfasalazine.
AB  - In this modification of the title compound, 5-(4-[(2
      pyridylamino)sulfonyl]phenyldiazenyl)salicylic acid, C(18)H(14)N(4)O(5)S, the
      molecule is present in the amide tautomeric form. Two azo-bridged phenyl rings
      render the bulk of the molecule planar, with the carboxylic acid group at one
      terminal and the pyridylamino residue at the other. The repeating unit in the
      crystal is a centrosymmetric dimer containing two identical R-2/2-(8) hydrogen
      bonded ring systems, each involving the carboxylic acid and pyridylamino
      moieties. Additional stabilization is due to an intramolecular hydrogen bond
      between the 2-hydroxyl group and the carbonyl O atom of the carboxylic acid
      group, as well as intermolecular pi-pi stacking.

PMID- 11313587
TI  - Anti-inflammatory drugs. IX. Hydrated diethylammonium (2-(2,6
      dichlorophenylamino)phenyl)acetate (HDEA.D.H2O).
AB  - In the solid-state structure of the title compound,
      C(4)H(12)N(+).C(14)H(10)Cl(2)NO(2)(-).H(2)O, the asymmetric unit contains one
      cation, one anion and a water molecule. A complex network of hydrogen bonds is
      present. A comparison is made with the structure of the anhydrous salt.

PMID- 11313588
TI  - 3,3'-Selenobis(propionic acid).
AB  - In contrast to Se[CH(2)C(O)OH](2) versus S[CH(2)C(O)OH](2), the title compound,
      Se[CH(2)CH(2)C(O)OH](2) or C(6)H(10)O(4)Se, is structurally quite similar to its
      sulfur analogue. The molecule has twofold symmetry. The C-Se-C bond angle is
      96.48 (8) degrees and the Se-C bond lengths are 1.9610 (14) A. The shortest Se.O
      intermolecular distance is 3.5410 (11) A. The O.O distances in the carboxylic
      acid dimers are 2.684 (2) A. The temperature dependence of the IR spectrum
      suggests tautomerism in the solid state.

PMID- 11313589
TI  - Dimethyl dispiro[tricyclo[3.3.1.1(3,7)]-decane-1,2'-bicyclo[1.1.0]butane-4',1"
      tricyclo[3.3.1.1(3,7)]decane-1',3'-dicarboxylate, a strain-enhanced
      bicyclo[1.1.0]butane with a very short intramolecular C--H...H--C contact.
AB  - The title molecule, C(26)H(34)O(4), shows a very short repulsive intramolecular C
      H.H-C contact, with an H.H distance of only 1.71 A. The flap angle varphi of the
      bicyclo[1.1.0]butane group is widened to 131.23 (8) degrees. Both methylene C
      atoms show tilt angles of 6.1 degrees. Bond lengths in the fused cyclopropane
      rings range from 1.501 (1) to 1.542 (1) A and are influenced by pi interactions
      with the carboxylate substituents.

PMID- 11313590
TI  - Two diastereomers of 9-(2,6-dichlorophenyl)-4a-hydroxy-3,3,6,6-tetramethyl
      1,2,3,4,4a,5,6,7,8,9a-decahydroxanthene-1,8-dione in the same crystal.
AB  - The reaction of dimedone with 2,6-dichlorobenzaldehyde leads to the title
      compound, C(23)H(26)Cl(2)O(4). In principle, the reaction could yield eight
      different stereoisomers. We have found four of them in the same crystal as two
      enantiomeric pairs of diastereomers, which means that the asymmetric unit is
      built up of two different diastereomers. Two of the three chiral centres display
      the same configuration, while the third is different in the two molecules in the
      asymmetric unit. The packing of the molecules is stabilized by hydrogen bonds
      between the hydroxy group and the carbonyl group attached to the cyclohexene
      ring, forming chains in which the different diastereomers alternate.

PMID- 11313591
TI  - Packing considerations of bis-dimedone derivatives.
AB  - We have determined the crystal structures of 2,2'-(4-fluorophenyl)methylenebis(3
      hydroxy-5,5-dimethyl-2-cyclohexen-1-one), C(23)H(27)FO(4), (I), 2,2'-(4
      chlorophenyl)methylenebis(3-hydroxy-5,5-dimethyl-2-cyclohexen-1-one),
      C(23)H(27)ClO(4), (II), 2,2'-(4-hydroxyphenyl)methylenebis(3-hydroxy-5,5-dimethyl
      2-cyclohexen-1-one), C(23)H(28)O(5), (III), 2,2'-(4-methylphenyl)methylenebis(3
      hydroxy-5,5-dimethyl-2-cyclohexen-1-one), C(24)H(30)O(4), (IV), 2,2'-(4
      methoxyphenyl)methylenebis(3-hydroxy-5,5-dimethyl-2-cyclohexen-1-one),
      C(24)H(30)O(5), (V), and 2,2'-(4-N,N'-dimethylaminophenyl)methylenebis(3-hydroxy
      5,5-dimethyl-2-cyclohexen-1-one), C(25)H(33)NO(4), (VI). Structures (III) to (VI)
      of these bis-dimedone derivatives show nearly the same packing pattern
      irrespective of the different substituent in the para position of the aromatic
      ring. However, (II) does not fit into this scheme, although the Cl atom is a
      substituent not too different from the others. The different packing of the
      fluoro compound, (I), can be explained by the fact that it crystallizes with two
      molecules in the asymmetric unit, which show a different conformation of the
      dimedone ring. On the other hand, (I) shows a similar packing pattern to bis(2
      hydroxy-4,4-dimethyl-6-oxo-1-cyclohexenyl)phenylmethane, a compound containing an
      aromatic ring without any substituent and with Z' = 2.

PMID- 11313592
TI  - N-Propionylhydroxylamine forms a three-dimensional hydrogen-bonded framework
      structure.
AB  - The title compound, N-hydroxypropanamide, C(3)H(7)NO(2), crystallizes with Z' = 3
      in P2(1)/c. The molecules are linked by three N-H.O hydrogen bonds [N.O 2.8012
      (16) to 2.8958 (15) A; N-H.O 163 to 168 degrees ] and by three O-H.O hydrogen
      bonds [O.O 2.6589 (15) to 2.6775 (17) A; O-H.O 165 to 177 degrees ] into a single
      three-dimensional framework.

PMID- 11313593
TI  - Hydrogen bonding in substituted nitroanilines: isolated nets in 1,3-diamino-4
      nitrobenzene and continuously interwoven nets in 3,5-dinitroaniline.
AB  - Molecules of 1,3-diamino-4-nitrobenzene, C(6)H(7)N(3)O(2), are linked by N-H.O
      hydrogen bonds [N.O 2.964 (2) and 3.021 (2) A; N-H.O 155 and 149 degrees] into
      (4,4) nets. In 3,5-dinitroaniline, C(6)H(5)N(3)O(4), where Z' = 2, the molecules
      are linked by three N-H.O hydrogen bonds [N.O 3.344 (2)-3.433 (2) A and N-H.O 150
      167 degrees] into deeply puckered nets, each of which is interwoven with its two
      immediate neighbours.

PMID- 11313594
TI  - Aminopyrimidine-carboxyl(ate) interactions in trimethoprim maleate, an antifolate
      drug.
AB  - In the title cocrystal, trimethoprim maleate [2,4-diamino-5-(3,4,5
      trimethoxybenzyl)pyrimidin-1-ium maleate], C(14)H(19)N(4)O(3)(+).C(4)H(3)O(4)(-),
      the trimethoprim molecule is protonated at N1. The carboxyl group of the maleate
      ion makes a specific double hydrogen bond of type N-H.O with the 2-amino group
      and the protonated N1 atom of the trimethoprim cation which is similar to the
      carboxylate-trimethoprim cation interaction observed in the complex of
      dihydrofolate reductase with trimethoprim. The pyrimidine moieties of
      trimethoprim cations are centrosymmetrically paired through a pair of N-H.N
      hydrogen bonds involving the 4-amino group and the pyridinium N3 atom of a
      symmetry-related molecule. One of the O atoms at the maleate carboxylate group
      bridges the 2-amino and 4-amino groups on either side of the paired trimethoprim
      cations. The other O atom of the carboxylate group forms an intramolecular O-H.O
      hydrogen bond with the carboxyl group. These characteristic hydrogen bonds result
      in infinite two-dimensional aggregation of rings into a supramolecular ladder,
      which is further crosslinked through weak C-H.O interactions with methoxy groups
      of neighbouring trimethoprim molecules to form a layered structure.

PMID- 11313595
TI  - [Azole. 45(1). Uber 2,4-Dinitrophenylhydrazone von
      Morpholinonitroimidazolderivaten].
AB  - The three title compounds, namely (Z)-1-(4,5-dinitroimidazol-1-yl)-3
      morpholinopropan-2-one 2,4-dinitrophenylhydrazone, C(16)H(17)N(9)O(9), (IV), (Z)
      3-morpholino-1-(4-morpholino-5-nitroimidazol-1-yl)propan-2-one 2,4
      dinitrophenylhydrazone, C(20)H(25)N(9)O(8), (Va), and (E)-3-morpholino-1-(4
      morpholino-5-nitroimidazol-1-yl)propan-2-one 2,4-dinitrophenylhydrazone
      tetrahydrofuran solvate, C(20)H(25)N(9)O(8).C(4)H(8)O, (Vb), have been prepared
      and their structures determined. In (IV), the C-4 nitro group is nearly
      perpendicular to the imidazole ring and the C-4-NO(2) bond length is comparable
      to the value for a normal single Csp(2)-NO(2) bond. In (IV), (Va) and (Vb), the C
      5 nitro group deviates insignificantly from the imidazole plane and the C-5-NO(2)
      bond length is far shorter in all three compounds than C-4-NO(2) in (IV). In
      consequence, the C-4 nitro group in (IV) is easily replaced by morpholine, while
      the C-5 nitro group in (IV), (Va) and (Vb) shows an extraordinary stability on
      treatment with the amine. The E configuration in (Vb) is stabilized by a three
      centre hydrogen bond.

PMID- 11313596
TI  - Two trans-4-aminoazoxybenzenes.
AB  - Two isomeric trans-4-aminoazoxybenzenes, trans-1-(4-aminophenyl)-2-phenyldiazene
      2-oxide (alpha, C(12)H(11)N(3)O) and trans-2-(4-aminophenyl)-1-phenyldiazene 2
      oxide (beta, C(12)H(11)N(3)O), have been characterized by X-ray diffraction. The
      alpha isomer is almost planar, having torsion angles along the C(aryl)-N bonds of
      only 4.9 (2) and 8.0 (2) degrees. The relatively short C(aryl)-N bond to the non
      oxidized site of the azoxy group [1.401 (2) A], together with the significant
      quinoid deformation of the respective phenyl ring, is evidence of conjugation
      between the aromatic sextet and the pi-electron system of the azoxy group. The
      geometry of the beta isomer is different. The non-substituted phenyl ring is
      twisted with respect to the NNO plane by ca 50 degrees, whereas the substituted
      ring is almost coplanar with the NNO plane. The non-oxidized N atom in the beta
      isomer has increased sp(3) character, which leads to a decrease in the N-N-C bond
      angle to 116.8 (2) degrees, in contrast with 120.9 (1) degrees for the alpha
      isomer. The deformation of the C-C-C angles (1-2 degrees ) in the phenyl rings at
      the substitution positions is evidence of the different character of the oxidized
      and non-oxidized N atoms of the azoxy group. In the crystal structures, molecules
      of both isomers are arranged in chains connected by weak N-H.O (alpha and beta)
      and N-H.N (beta) hydrogen bonds.

PMID- 11313597
TI  - 3,9-Bis(dicyanomethylene)-2,4,8,10-tetrathiaspiro[5.5]undecane.
AB  - The title compound, 2,2'-(2,4,8,10-tetrathiaspiro[5.5]undecane-3,9
      diylidene)bis(propanedinitrile), C(13)H(8)N(4)S(4), has been designed and
      synthesized for use as a potential new organic molecular electronic material. The
      spiro-annulated structure has twofold symmetry and is formed by two equal push
      pull ethylene units, with the cycloalkylthio groups as electron donors and the
      cyano groups as electron acceptors. The intermolecular S.N non-bonded separation
      within a layer in the lattice is 3.296 (6) A, indicating a strong intermolecular
      interaction between the cyano groups and the S atoms, while the S atoms in two
      neighbouring molecules have a shortest S.S contact of 3.449 (3) A. In addition,
      attractive C-H.N and C-H.S interactions bridge adjacent molecules either within a
      layer or between layers. In short, these four types of intermolecular
      interactions combine to form an extended three-dimensional network in the
      lattice, resulting in a highly ordered array of molecular packing.

PMID- 11313598
TI  - 3',4'-Bis(4-chlorophenyl)spiro[chroman-3,5'(4'H)-isoxazol]-4-one.
AB  - The title compound, C(23)H(15)Cl(2)NO(3), crystallizes with two independent
      molecules in the asymmetric unit. The chromanone moiety consists of a benzene
      ring fused with a six-membered heterocyclic ring which adopts a sofa
      conformation. The five-membered spiroisoxazoline ring is in an envelope
      conformation. The p-chlorophenyl rings bridged by the five-membered ring are
      nearly perpendicular to each other. The chromanone moiety of one molecule packs
      into the cavity formed by the p-chlorophenyl rings of a second molecule through
      the formation of C-H.pi interactions. The structure is stabilized by weak C-H.O,
      C-H.Cl and C-H.pi interactions.

PMID- 11313599
TI  - 1:2 Complexes of chloranilic acid with pyrazole and imidazole, and the
      acetonitrile solvate of a 1:1 complex with imidazole.
AB  - 2,5-Dichloro-3,6-dihydroxy-1,4-benzoquinone (chloranilic acid) forms X-H.Y (X, Y
      = N or O) and C-H.Cl hydrogen bonds with pyrazole and imidazole to afford
      bis(pyrazolium) dichloroanilate and bis(imidazolium) dichloroanilate, (I) and
      (II), both 2C(3)H(5)N(2)(+).C(6)Cl(2)O(4)(2-), and imidazolium chloroanilate
      acetonitrile solvate, C(3)H(5)N(2)(+).C(6)HCl(2)O(4)(-).C(2)H(3)N, (III). Their
      crystal structures demonstrate three novel supramolecular architectures based on
      supramolecular synthons to build a ladder, (I), a two-dimensional network, (II),
      and a flat ribbon, (III).

PMID- 11313600
TI  - Two stereoisomeric pentacyclic oxindole alkaloids from Uncaria tomentosa:
      uncarine C and uncarine E.
AB  - The chloroform solvate of uncarine C (pteropodine), (1'S,3R,4'aS,5'aS,10'aS)
      1,2,5',5'a,7',8',10',10'a-octahydro-1'-methyl-2-oxospiro[3H-indole-3,6'(4'aH)
      [1H]pyrano[3,4-f]indolizine]-4'-carboxylic acid methyl ester,
      C(21)H(24)N(2)O(4).CHCl(3), has an absolute configuration with the spiro C atom
      in the R configuration. Its epimer at the spiro C atom, uncarine E
      (isopteropodine), (1'S,3S,4'aS,5'aS,10'aS)-1,2,5',5'a,7',8',10',10'a-octahydro-1'
      methyl-2-oxospiro[3H-indole-3,6'(4'aH)-[1H]pyrano[3,4-f]indolizine]-4'-carboxylic
      acid methyl ester, C(21)H(24)N(2)O(4), has Z' = 3, with no solvent. Both form
      intermolecular hydrogen bonds involving only the oxindole, with N.O distances in
      the range 2.759 (4)-2.894 (5) A.

PMID- 11313601
TI  - Absolute configuration of (+)-(S)-2-(5-fluoro-2-methoxy-1,4-benzodioxan-2
      yl)imidazolinium bromide.
AB  - The title compound, C(12)H(14)FN(2)O(3)(+).Br(-), crystallizes in the non
      centrosymmetric P2(1)2(1)2(1) space group. The absolute configuration of the
      pharmacologically active molecule could be resolved in the hydrobromide salt, the
      structure of which is reported. The molecule of the title compound has the S
      configuration. The molecular packing in the crystal is stabilized by weak N-H.Br
      [N.Br = 3.240 (4) and 3.302 (4) A] hydrogen bonding.

PMID- 11313602
TI  - 5-Chloro-N-(2-hydroxy-5-methylphenyl)salicylaldimine.
AB  - The title compound, N-(5-chloro-2-oxidobenzylidene)-2-hydroxy-5-methylanilinium,
      C(14)H(12)ClNO(2), is a tridentate Schiff base with almost planar molecules. Each
      molecule contains a strong intramolecular N-H.O hydrogen bond [2.576 (2) A].
      There is also an intermolecular O-H.O hydrogen bond [2.695 (2) A] linking
      neighbouring molecules into infinite chains along the [101] direction.

PMID- 11313603
TI  - Benzyl tert-butoxycarbonyl-alpha-aminoisobutyrate.
AB  - The small synthetic peptide, benzyl 2-(tert-butoxycarbonyl-amino)isobutyrate,
      C(16)H(23)NO(4), has the alpha-helical conformation [/varphi/ = 55.8 (2) degrees
      and /psi/ = 37.9 (2) degrees] observed in peptide fragments of peptaibols
      containing the alpha-aminoisobutyric acid (Aib) residue. The structure shows no
      intramolecular hydrogen bonding, which would disrupt the limited conformational
      freedom associated with this amino acid. Two weak intermolecular hydrogen
      contacts are observed.

PMID- 11313604
TI  - Bis[4-(2-pyridylmethyleneamino)-phenyl] ether.
AB  - The title compound, C(24)H(18)N(4)O, is a bis-bidentate Schiff base ligand
      exhibiting pseudo-C(2) symmetry. The molecule is twisted about the central ether
      linkage and exhibits an imine E configuration. In the crystal, the molecules are
      linked by weak intermolecular C-H.N hydrogen bonds.

PMID- 11313605
TI  - Cyclohexylammonium 2'-hydroxy-2-biphenyl phosphonate.
AB  - In the molecular structure of the title compound, C(6)H(14)N(+).C(12)H(10)O(4)P(
      ), three O atoms are bonded to phosphorus. The oxygen connected to the biphenoxy
      residue is not involved in hydrogen bonding; of the other two, one oxygen is
      involved in intermolecular hydrogen bonding to an N-H group as well as the O-H
      group of the biphenoxy residue, while the second oxygen is involved in hydrogen
      bonding to two N-H groups.

PMID- 11313606
TI  - 3-Phenyl-4H-furo[3,2-C]chromen-4-one.
AB  - The crystal structure of the title compound, C(17)H(10)O(3), is the first example
      of a furocoumarin containing three fused rings. The tricyclic furocoumarin
      fragment is perfectly planar. The phenyl substituent forms a dihedral angle of
      39.52 (8) degrees with the plane of the tricyclic system. The crystal packing
      involves centrosymmetric dimers interconnected by strong pi-interactions between
      their furo[3,2-c]coumarin fragments [at distances of 3.42 (4) A].

PMID- 11313607
TI  - Two 17-hydroxy-9(10-->5)-abeo-estr-4-ene-3,10-diones.
AB  - (5S,9S,17S)-17-Hydroxy-9(10-->5)-abeo-estr-4-ene-3,10-dione, C(18)H(26)O(3),
      (II), and (5R,9R,17S)-17-hydroxy-9(10-->5)-abeo-estr-4-ene-3,10-dione,
      C(18)H(26)O(3), (III), are equimolecular products of the Fe(II)-induced
      transposition of 10beta-hydroperoxy-17beta-hydroxyestr-4-en-3-one, (I). With
      respect to reagent molecules, the configuration at C9 is retained for (II) while
      it is inverted in (III). The conformations of the five- and six-membered rings
      are compared.

PMID- 11313608
TI  - (3R,4aS,5R)-3-Hydroxy-5-isopropenyl-3,8-dimethyl-4,4a,5,6-tetrahydro-2(3H)
      naphthalenone.
AB  - In the crystal structure of C(15)H(20)O(2), molecules are associated by
      intermolecular hydrogen bonds between the hydroxy function and a keto group [O.O
      2.770 (2) A], forming chains along the [100] direction in the crystal. Both six
      membered rings in the decalin unit adopt envelope conformations; one section of
      the molecule, encompassing the extended conjugation of a C=C double bond with an
      enone functionality [C=C-C=O = 175.6 (2) degrees and C=C-C=C = 176.6 (2) degrees
      ], is flat, whilst the rest of the molecule is folded relative to the constrained
      part. The stereochemistry was determined from the R-(-)-carvone starting
      material.

PMID- 11313610
TI  - Ultrasonic indentation: a procedure for the noninvasive quantification of force
      displacement properties of the lumbar spine.
AB  - BACKGROUND: Alterations in the normal force-displacement (FD) properties of
      spinal tissues have been associated with specific forms of pathology, such as
      degenerative disk disease. Unfortunately, few current procedures exist that
      assess spinal FD properties in an accurate, reliable, and noninvasive manner.
      Consequently, the clinical relevance of the relation between spinal disorders and
      spinal FD properties is not fully understood. OBJECTIVE: To investigate the
      accuracy and reliability of spinal FD measures obtained through use of a
      procedure in which real-time ultrasonic imaging (ultrasonic indentation) is used
      during load-controlled external indentation. SETTING: McCaig Centre for Joint
      Injuries and Arthritis Research, University of Calgary. METHODS: The bench-top
      accuracy and reliability of ultrasonic indentation were assessed by cyclic
      indentation of a spring-mounted platform. These data were compared with criterion
      data derived from a materials testing machine. A porcine preparation was then
      used to assess the accuracy of ultrasonic indentation-generated estimates of
      vertebral displacement in comparison with a criterion of optically tracked
      displacement. In addition, previously unreported parameters relating to
      indentation accuracy (frame deflection and off-axis loading) were characterized.
      RESULTS: Reliability of ultrasonic indentation ranged between 0.99 and 1.00
      (intraclass correlation coefficient). Error values in force, displacement, and
      stiffness ranged from 0.81% to 13.62% over varying experimental conditions.
      CONCLUSIONS: Ultrasonic indentation is a unique procedure that is capable of
      assessing, noninvasively, FD properties of spinal tissues, including vertebral
      displacement in the indentation plane. The results of this study suggest that
      ultrasonic indentation is a potentially useful technique for quantifying spinal
      FD properties in vivo.

PMID- 11313611
TI  - Prevalence of nonmusculoskeletal complaints in chiropractic practice: report from
      a practice-based research program.
AB  - OBJECTIVE: To identify patient and practice characteristics that might contribute
      to people's seeking chiropractic care for nonmusculoskeletal complaints. DESIGN:
      This was a cross-sectional study conducted through the methods of practice-based
      research. SETTING: Data were collected in 1998--1999 in chiropractic offices in
      the United States, Canada, and Australia; data were managed by a practice-based
      research office operating in a chiropractic research center. POPULATION: The
      subjects were new and established patients of all ages who visited the
      participating offices during a designated data collection week. DATA ANALYSIS:
      Multiple logistic regression was used to examine factors associated with
      patients' presenting for nonmusculoskeletal chief complaints. Pearson's chi(2)
      test was used to examine associations among practice variables and the proportion
      of patients with nonmusculoskeletal chief complaints. RESULTS: A total of 7651
      patients of 161 chiropractors in 110 practices in 32 states and 2 Canadian
      provinces participated; data from 2 Australian practices were included in the
      totals but not in the analysis. Nonmusculoskeletal complaints accounted for 10.3%
      of the chief complaints. The following characteristics made patients more likely
      to present with nonmusculoskeletal chief complaints: being less than 14 years of
      age (adjusted odds ratio [AOR], 6.9; 95% CI, 5.2--9.1); being female (AOR, 1.5;
      CI, 1.3--1.8); presenting in a small town/rural location (AOR, 1.9; CI, 1.3-
      2.7); reporting more than 1 complaint, especially nonmusculoskeletal complaints
      (AOR, 4.9; CI, 3.9--6.0); having received medical care for the chief complaint
      (AOR, 3.4; CI, 2.9--4.1); and having first received chiropractic care before 1960
      (AOR, 1.7; CI, 1.1--2.4). Practices with the highest proportion of patients with
      nonmusculoskeletal chief complaints (>17%) were less likely to accept insurance
      and more likely to be in locations with populations greater than 100,000. They
      used the most common chiropractic adjustive techniques less frequently and used
      more nonadjustive procedures, especially diet/nutrition counseling, nutritional
      supplementation, herbal preparations, naturopathy, and homeopathy. CONCLUSIONS:
      Drawing on practices with the patient and practice characteristics identified in
      this study to conduct outcomes studies on nonmusculoskeletal conditions is a
      possible direction for future research.

PMID- 11313612
TI  - Evaluating the quality of clinical practice guidelines.
AB  - OBJECTIVE: To review and identify established methods for evaluating the quality
      of practice guidelines and to use a selected assessment tool to assess 2
      chiropractic practice guideline documents. METHODS: A search of the medical
      literature was performed to identify current methods and procedures for practice
      guideline evaluation. Two chiropractic practice guideline documents, Vertebral
      Subluxation in Chiropractic Practice (CCP) and Guidelines for Chiropractic
      Quality Assurance and Practice Parameters (Mercy) were then independently
      evaluated for validity by 10 appraisers using the identified appraisal tool. The
      appraisal scores were tabulated, and consensus appraisals were generated for the
      CCP and Mercy guideline documents. RESULTS: The "Appraisal Instrument for
      Clinical Guidelines" (Cluzeau instrument) was identified as a reliable and valid
      method of guideline evaluation. The result of the application of this appraisal
      tool in the assessment of the CCP and Mercy guideline documents was that the
      former scored notably lower than the latter. On the basis of the results of the
      guideline appraisals, the CCP document is not recommended, and its guidelines are
      not considered suitable for application in chiropractic practice. The Mercy
      guidelines are recommended for application in chiropractic practice, with the
      proviso that new scientific data should be considered. CONCLUSIONS: The
      literature reviewed suggests that professional organizations or groups should
      undertake a critical review of guidelines using available critical guideline
      appraisal tools. Guideline validity appraisal should be done before acceptance by
      the chiropractic profession. To avoid unwarranted utilization of poorly
      constructed guidelines, it is strongly recommended that all future guidelines be
      reviewed for validity and scientific accuracy with the findings published in a
      medically indexed journal before they are adopted by the chiropractic community.

PMID- 11313613
TI  - An inquiry into chiropractors' intention to treat adolescent idiopathic
      scoliosis: a telephone survey.
AB  - BACKGROUND: The primary aim of this study was to (1) determine the clinical
      management approach of practicing chiropractors with regard to patients with
      adolescent idiopathic scoliosis and (2) measure the response rate of a telephone
      survey. METHODS: A survey instrument was developed and pretested, and a case
      specific clinical vignette was generated for a hypothetical typical 12-year-old
      girl with adolescent idiopathic scoliosis. The instrument addressed 3 domains:
      the specific management of idiopathic scoliosis, elements guiding the general
      selection of treatment recommendations, and demographics of respondents. The
      sample frame consisted of 62,000 US chiropractors, of whom 165 were randomly
      selected for the survey sample. Interviews were conducted by telephone through
      use of the tested survey instrument. RESULTS: The response rate was 69%
      (114/165). Of the 51 nonrespondents, 15 did not have a listed business telephone
      number and 24 were not in active practice. The response rate of those who met the
      inclusion criteria (practicing chiropractor with a listed telephone number) was
      90% (114/126). The gender, chiropractic college, and years in practice of
      respondents in this survey were similar to those of respondents in 3 other
      national surveys. In general, the respondents would provide 6 months of
      "intensive" chiropractic therapy, then follow the patient for 4 years (near
      skeletal maturity). Eighty-two percent of respondents named diversified technique
      as their primary adjustive treatment, 87% would use exercise, and 30% would use
      electric muscle stimulation as an adjunct to manual therapy. CONCLUSION: Most
      surveyed chiropractors would use similar methods (frequency and length of
      treatment, manipulation technique, and exercise) in the treatment of patients
      with adolescent idiopathic scoliosis. A high response rate to a national survey
      can be achieved through use of telephone contact.

PMID- 11313614
TI  - Intraexaminer and interexaminer reliability for palpation of the cranial rhythmic
      impulse at the head and sacrum.
AB  - BACKGROUND: A range of health care practitioners use cranial techniques.
      Palpation of a cranial rhythmic impulse (CRI) is a fundamental clinical skill
      used in diagnosis and treatment with these techniques. There has been little
      research establishing the reliability of CRI rate palpation. OBJECTIVE: This
      study aimed to establish the intraexaminer and interexaminer reliability of CRI
      rate palpation and to investigate the "core-link" hypothesis of craniosacral
      interaction that is used to explain simultaneous motion at the cranium and
      sacrum. DESIGN: Within-subjects, repeated-measures design. SUBJECTS: Two
      registered osteopaths, both with postgraduate training in diagnosis and
      treatment, using cranial techniques, palpated 11 normal healthy subjects.
      METHODS: Examiners simultaneously palpated for the CRI at the head and the sacrum
      of each subject. Examiners indicated the "full flexion" phase of the CRI by
      activating silent foot switches that were interfaced with a computer. Subject
      arousal was monitored using heart rate. Examiners were blind to each other's
      results and could not communicate during data collection. RESULTS: Reliability
      was estimated from calculation of intraclass correlation coefficients (2,1).
      Intrarater reliability for examiners at either the head or the sacrum was fair to
      good, significant intraclass correlation coefficients ranging from +0.52 to
      +0.73. Interexaminer reliability for simultaneous palpation at the head and the
      sacrum was poor to nonexistent, ICCs ranging from -0.09 to +0.31. There were
      significant differences between rates of CRI palpated simultaneously at the head
      and the sacrum. CONCLUSIONS: The results fail to support the construct validity
      of the "core-link" hypothesis as it is traditionally held by proponents of
      craniosacral therapy and osteopathy in the cranial field.

PMID- 11313615
TI  - The effect of chiropractic care on jet lag of Finnish junior elite athletes.
AB  - OBJECTIVE: To determine the effect of chiropractic care on jet lag in Finnish
      junior elite athletes. SUBJECTS: Fifteen Finnish junior elite athletes. METHODS:
      Through use of a table of random numbers, each athlete was assigned by sex to one
      of 3 groups: chiropractic adjustment, sham adjustment, or control. As needed, the
      chiropractic adjustment group athletes (n = 5) were adjusted on a daily basis by
      licensed chiropractors using a toggle/recoil procedure. The sham adjustment group
      athletes (n = 5) received sham adjustments on a daily basis by licensed
      chiropractors. The control group athletes (n = 5) were not adjusted or sham
      adjusted but participated in all test protocols. Sleep, jet lag, chiropractic,
      and mood data (the last acquired through use of the Profile of Mood States) were
      collected on a daily basis for 18 consecutive days. RESULTS: Repeated-measures
      analyses of variance (3 x 2) of total mood disturbance scores and heart rate
      variables indicated that there were no significant (.05 level) between-group
      differences. Sleep data were analyzed through use of a 3 x 2, repeated-measures
      multivariate analysis of variance. Pillai's trace indicated that there were no
      between-group differences. Self-assessment of jet lag by participants after
      traveling to Georgia and after returning to Finland showed no between-group
      differences. CONCLUSIONS: It was concluded that chiropractic care did not reduce
      the effects of jet lag.

PMID- 11313616
TI  - Epilepsy and seizure disorders: a review of literature relative to chiropractic
      care of children.
AB  - OBJECTIVE: To review the currently available literature regarding chiropractic
      care relative to patients with epilepsy, particular emphasis being placed on
      those who have epilepsy as children. DATA SOURCES: The Index to Chiropractic
      Literature was searched for the years 1980 through 1998 through use of the
      keywords epilepsy and seizure. The MANTIS database was searched for the years
      1970 through 2000 through use of the Medical Subject Heading (MeSH) keywords
      chiropractic, epilepsy, seizure, and child/children. In addition, a MEDLINE
      search of the literature was performed for the years 1966 through 2000 through
      use of the same subject headings. RESULTS: The present study reviews 17 reports
      of pediatric epileptic patients receiving chiropractic care. Fourteen of the 17
      patients were receiving anticonvulsive medications, which had proven unsuccessful
      in the management of the condition. Upper cervical care to correct vertebral
      subluxation was administered to 15 patients, and all reported positive outcomes
      as a result of chiropractic care. CONCLUSIONS: Chiropractic care may represent a
      nonpharmaceutical health care approach for pediatric epileptic patients. Current
      anecdotal evidence suggests that correction of upper cervical vertebral
      subluxation complex might be most beneficial. It is suggested that chiropractic
      care be further investigated regarding its role in the overall health care
      management of pediatric epileptic patients.

PMID- 11313617
TI  - Treatment of cervical radiculopathy with flexion distraction.
AB  - OBJECTIVE: To discuss the nonsurgical treatment of a cervical disk herniation
      with flexion distraction manipulation. CLINICAL FEATURES: A case study of
      cervical disk syndrome with radicular symptoms is presented. Magnetic resonance
      imaging revealed a large C5-C6 disk herniation. Degenerative changes at the
      affected level were demonstrated on cervical spine plain film radiographs.
      INTERVENTION AND OUTCOME: The patient received treatment in the form of flexion
      distraction manipulation and adjunctive therapies. A complete resolution of the
      patient's subjective complaints was achieved. CONCLUSION: Flexion distraction has
      been a technique associated with musculoskeletal conditions of the lumbar spine.
      Flexion distraction applied to the cervical spine might be an effective therapy
      in the treatment of cervical disk herniations. Although further controlled
      studies are needed, treatment of cervical disk syndromes with flexion distraction
      might be a viable form of conservative care.

PMID- 11313618
TI  - A missed Jefferson fracture in chiropractic practice.
AB  - OBJECTIVE: To review the case of a missed cervical spine fracture in a patient
      with neck pain. CLINICAL FEATURES: A 21-year-old thatcher with neck pain
      presented to a chiropractic clinic after a fall from a roof 4 m high. The
      hospital radiographs were read as normal. The chiropractor suspected a Jefferson
      fracture of the atlas after evaluation of the same radiographs. INTERVENTION AND
      OUTCOME: The chiropractor retook the anteroposterior open-mouth radiograph to
      confirm the suspected fracture. The patient was referred for further imaging and
      underwent neurosurgical treatment, after which he recovered well. CONCLUSION:
      Normal radiologic reports from a hospital cannot be relied on for
      contraindications to manipulative treatment in all instances, as shown in this
      case of a missed fracture. Chiropractors should therefore always evaluate
      radiographs that are brought to them.

PMID- 11313619
TI  - Evidence-based clinical guidelines for the management of acute low back pain:
      response to the guidelines prepared for the Australian Medical Health and
      Research Council.

PMID- 11313620
TI  - Biomechanics of the central nervous system: spinal canal deformations and changes
      in posture.

PMID- 11313622
TI  - WHO seeking nurses' input. World Health Organization.

PMID- 11313623
TI  - Could the nurse be an endangered species?

PMID- 11313624
TI  - Acute management of the patient with spinal cord injury.
AB  - Spinal cord injuries are not as common as many other types of injuries. The
      victims are often young, the injury debilitating, and the effects devastating and
      incalculable. The acute management of patients with spinal cord injury can
      significantly affect the patient's eventual neurologic and functional outcome and
      ultimately their quality of life. Early interventions are aimed at reestablishing
      physiologic homeostasis, lessening the amount of secondary injury, and preserving
      neurologic function.

PMID- 11313625
TI  - Establishing a collaborative trauma training program with a community trauma
      center for military nurses.
AB  - A mission of the Navy Nurse Corps is to deploy medical support for military
      forces on short notice. Navy nurses must possess a working knowledge of trauma
      management, but meeting this clinical experience is a challenge. Peacetime
      military hospitals do not routinely care for severely injured patients. This
      article describes how the Navy established a partnership with a Level 1 Trauma
      Center, the role and expectations for both Navy and civilian nurses, and an
      evaluation of the experience.

PMID- 11313626
TI  - Beverly Malone discusses health care and nursing issues. Interview by Joanne
      Ingalls McKay.

PMID- 11313628
TI  - Interdisciplinary practice: spinal cord injury.

PMID- 11313627
TI  - Unintentional strangulation in children: a professional approach to the problem.
AB  - Unintentional strangulation in children is a preventable cause of injury. Health
      care providers caring for injured children may not always consider the positive
      impact that they can have after such an incident. After caring for a child who
      had experienced a life-threatening accident involving a cable tie, the author
      explored the options available to health care providers in preventing similar
      incidences in other children.

PMID- 11313629
TI  - Injury prevention and control: understanding the issues and making a difference.

PMID- 11313630
TI  - Medical device adverse events and the temporary invasive cardiac pacemaker.

PMID- 11313631
TI  - What you should know about spinal cord injuries.

PMID- 11313632
TI  - Effect of a second bloodmeal on the oesophagus colonization by Leishmania
      mexicana complex in Lutzomyia evansi (Diptera: Psychodidae).
AB  - Migration and colonization of the oesophagus by Leishmania mexicana parasites
      were enhanced after digestion of a second bloodmeal intake in Lutzomyia evansi.
      This event has epidemiological significance since it affects the infection
      susceptibility of this sand fly species, which is a proven vector of L. chagasi
      in Colombian and Venezuelan visceral leishmaniasis foci. Also, it may explain the
      host seeking behaviour displayed by some partially bloodfed flies found inside
      houses.

PMID- 11313633
TI  - Visceral leishmaniasis in the Metropolitan Region of Belo Horizonte, State of
      Minas Gerais, Brazil.
AB  - In the last few years the number of human cases of American visceral
      leishmaniasis in the Metropolitan Region of Belo Horizonte (MRBH), Minas Gerais,
      Brazil has increased, indicating an elevation in the transmission rate of the
      disease. The total number of notified human cases in the MRBH since 1994, when
      the first case was identified, up to 1999 was 345 of which 223 (65%) were from
      the city itself, indicating an urbanization of the disease in this region of
      Minas Gerais. The age distribution of visceral leishmaniasis cases in the MRBH
      shows a higher prevalence in children from 0-4 years old, responsible for 28.9%
      of the notifications. Clinical and immunological findings from dogs infected with
      Leishmania chagasi are described. The majority of these animals showed no sign of
      the disease. Sera from all infected dogs showed detectable Leishmania-induced
      high titles of antibodies based on the results of an indirect fluorescent
      antibody test. Samples of isolated Leishmania from human and dogs were
      characterized as L. (L.) chagasi by biochemical and molecular techniques.

PMID- 11313634
TI  - Geographical distribution of Biomphalaria snails in the State of Minas Gerais,
      Brazil.
AB  - Published and unpublished observations on geographical distribution of
      Biomphalaria snails in the State of Minas Gerais, Brazil, were compiled. This
      work is aimed at knowing the present occurrence of Biomphalaria species in this
      region, and at contributing to the elaboration of the planorbid chart of Minas
      Gerais. In malacological surveys, performed by several researchers, the presence
      of seven species of this genus was recorded. Those planorbids were found in 12
      mesoregions, in 283 (33.1%) municipalities out of 853 with the following
      distribution: B. glabrata (185 municipalities), B. straminea (125), B.
      tenagophila (58), B. peregrina (57), B. schrammi (26), B. intermedia (20) and B.
      occidentalis (2). B. glabrata and B. tenagophila are found naturally infected by
      Schistosoma mansoni in Minas Gerais. In 24 municipalities the three snail hosts
      of S. mansoni in Brazil, B. glabrata, B. tenagophila and B. straminea, are
      present.

PMID- 11313635
TI  - Prevalence and intensity of infections of Ascaris lumbricoides and Trichuris
      trichiura and associated socio-demographic variables in four rural Honduran
      communities.
AB  - Between January and March 1998, a cross-sectional survey was carried out in four
      rural communities in Honduras, Central America. We examined the prevalence and
      intensity of Ascaris lumbricoides and Trichuris trichiura infections among 240
      fecal specimens, and the association between selected socio-demographic variables
      and infection for 62 households. The overall prevalence of A. lumbricoides and T.
      trichiura was 45% (95% CI 39.0-51.9) and 38% (95% CI 31.8-44.4) respectively. The
      most intense infections for Ascaris and Trichuris were found in children aged 2
      12 years old. By univariate analysis variables associated with infections of A.
      lumbricoides were: number of children 2-5 years old (p=0.001), level of formal
      education of respondents (p=0.01), reported site of defecation of children in
      households (p=0.02), households with children who had a recent history of
      diarrhea (p=0.002), and the location of households (p=0.03). Variables associated
      with both A. lumbricoides and T. trichiura infection included: number of children
      6-14 years old (p=0.01, p=0.04, respectively), ownership of a latrine (p=0.04,
      p=0.03, respectively) and coinfection with either helminth (p=0.001, p=0.001,
      respectively). By multivariate analysis the number of children 2-5 years living
      in the household, (p=0.01, odds ratio (OR)=22.2), children with a recent history
      of diarrhea (p=0.0, OR=39.8), and infection of household members with T.
      trichiura (p=0.02, OR=16.0) were associated with A. lumbricoides infection. The
      number of children 6-14 years old in the household was associated with both A.
      lumbricoides and T. trichiura infection (p=0.04, p=0.01, OR=19.2, OR=5.2,
      respectively).

PMID- 11313636
TI  - First report of Lutzomyia (Nyssomyia) umbratilis Ward & Frahia, 1977 outside of
      Amazonian Region, in Recife, State of Pernambuco, Brazil (Diptera: Psychodidae:
      Phlebotominae).
AB  - Lutzomyia umbratilis, a known vector of Leishmania guyanensis in the north of
      Amazon basin, has been exclusively found in the Amazonian region. Here we report
      for the first time the occurrence of this species in northeastern Brazil. The
      epidemiological importance of the occurrence of this species in the Atlantic
      Forest is commented.

PMID- 11313637
TI  - The Phlebotominae sand fly (Diptera: Psychodidae) fauna of two Atlantic Rain
      Forest Reserves in the State of Rio de Janeiro, Brazil.
AB  - During two consecutive years, studies on the sand fly fauna in Poco das Antas and
      Fazenda Bom Retiro, two Atlantic Rain Forest Reserves from the State of Rio de
      Janeiro, were performed using Shannon traps, CDC light traps and human bait
      collections. Eleven species were identified; Lutzomyia longipalpis, L. migonei,
      L. edwardsi, L. intermedia, L. whitmani, L. fischeri, L. shannoni, L. ayrozai, L.
      hirsuta, L. monticola and L. misionensis (first occurrence in the State of Rio de
      Janeiro). L. intermedia and L. whitmani were the predominant anthropophilic
      species around houses, while L. hirsuta predominated in the forest.

PMID- 11313638
TI  - A new sand fly, Lutzomyia campograndensis sp. n. (Diptera: Psychodidae:
      Phlebotominae) from the State of Mato Grosso do Sul, Brazil.
AB  - During studies of the phlebotomine sand fly fauna of Campo Grande, State of Mato
      Grosso do Sul, Brazil, a new species was captured with CDC light trap and is
      described here. The new species resembles Lutzomyia lutziana (Costa Lima) and is
      named Lutzomyia campograndensis sp. n. after the type locality.

PMID- 11313639
TI  - Population biology of Allocreadium lobatum Wallin, 1909 (Digenea: Allocreadiidae)
      in the creek chub, Semotilus atromaculatus, mitchill (Osteichthyes: Cyprinadae),
      in a Nebraska Creek, USA.
AB  - Allocreadium lobatum Wallin, 1909 has been reported in cyprinid species of
      freshwater fish in Canada and in the United States. The population biology of A.
      lobatum in the host Semotilus atromaculatus Mitchill was studied from May through
      December 1991, in a USA creek. Overall prevalence (64%) and mean intensity (4.4
      +/- 0.4) were greater than previously reported while abundance, reported for the
      first time, was 2.8 +/- 0.3. Several trends in A. lobatum population biology as a
      function of S. atromaculatus length were identified. Mean intensity and abundance
      of A. lobatum increased with host size and significant differences in prevalence
      and A. lobatum lengths were found to correlate with host lengths.

PMID- 11313640
TI  - New host and locality records for Tetrameres (Gynaecophila) spirospiculum Pinto &
      Vicente, 1995 (Nematoda: Tetrameridae), with new morphological data.
AB  - We report the finding of Tetrameres spirospiculum Pinto & Vicente, 1995 from
      Theristicus melanopis melanopis (Threskiornithidae) from Patagonia, Argentina.
      These constitute new host and locality records. We propose the assignation of
      this species to the subgenus T. (Gynaecophila) Gubanov, 1950, based on the
      presence of labia and the absence of cuticular flanges at the anterior end. Some
      new morphological data are provided, such as the arrangement of cuticular spines
      and the presence of a pair of somatic papillae at beginning of posterior third of
      body length. T. (G.) spirospiculum may probably be regarded as specific to birds
      of the genus Theristicus.

PMID- 11313641
TI  - Effect of interferon-alpha on experimental septal fibrosis of the liver - study
      with a new model.
AB  - Interferon-alpha is used in antiviral therapy in humans, mainly for viral
      hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even
      in the absence of anti-viral response, which suggests that interferon directly
      inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica
      regularly develop diffuse septal fibrosis of the liver, which terminates in
      cirrhosis 40 days after inoculation. The aim of this study was to test the anti
      fibrotic effect of interferon in this experimental model. Evaluation of fibrosis
      was made by three separate methods: semi-quantitative histology, computerized
      morphometry and hydroxyproline measurements. Treatment with interferon-alpha
      proved to inhibit the development of fibrosis in this model, especially when
      doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the
      anti-fibrotic potential of interferon-alpha on a non-viral new experimental model
      of hepatic fibrosis, a clear-cut dose-dependent effect was observed.

PMID- 11313642
TI  - Effect of Lutzomyia whitmani (Diptera: Psychodidae) salivary gland lysates on
      Leishmania (Viannia) braziliensis infection in BALB/c mice.
AB  - Previous reports showed that Lutzomyia longipalpis saliva exacerbate Leishmania
      braziliensis infection in mice. The sand fly Lu. whitmani is one of the vectors
      of L. (Viannia) braziliensis (LVb), a causative agent of cutaneous leishmaniasis
      in the State of Ceara, Brazil. To determine whether saliva of Lu. whitmani could
      increase the infectivity of LVb in mice, we inoculated groups of BALB/c mice with
      LVb promastigotes in the presence or absence of the salivary glands lysate from
      Lu. whitmani. We found that coinjection with Lu. whitmani saliva increased size
      but not longevity of cutaneous LVb lesions in BALB/c mice, since the formed
      lesions gradually resolved. The mechanism(s) by which Lu. whitmani saliva might
      exacerbate LVb infection in BALB/c mice is speculated.

PMID- 11313644
TI  - A theoretical model of the tridimensional structure of Bacillus thuringiensis
      subsp. medellin Cry 11Bb toxin deduced by homology modelling.
AB  - Cry11Bb is an insecticidal crystal protein produced by Bacillus thuringiensis
      subsp. medellin during its stationary phase; this partial differential-endotoxin
      is active against dipteran insects and has great potential for mosquito borne
      disease control. Here, we report the first theoretical model of the
      tridimensional structure of a Cry11 toxin. The tridimensional structure of the
      Cry11Bb toxin was obtained by homology modelling on the structures of the Cry1Aa
      and Cry3Aa toxins. In this work we give a brief description of our model and
      hypothesize the residues of the Cry11Bb toxin that could be important in receptor
      recognition and pore formation. This model will serve as a starting point for the
      design of mutagenesis experiments aimed to the improvement of toxicity, and to
      provide a new tool for the elucidation of the mechanism of action of these
      mosquitocidal proteins.

PMID- 11313643
TI  - Vaccination against Taenia solium cysticercosis.
AB  - Taenia solium is a parasite that causes human cysticercosis. Its life cycle
      includes the adult stage, the egg and the larval stage. Human cysticercosis is a
      disease related to underdevelopment, the main clinical manifestation is
      neurocysticercosis. Control measures include mass cestocidal treatment aimed to
      cure possible taeniosis cases. Although useful it has certain disadvantages, such
      as the generation of symptomatology in occult neurocysticercosis. Alternatively,
      health education has been shown to be highly effective since people become aware
      of the importance of human and porcine cysticercosis and the possibility of
      eliminating it. Nevertheless it has to be implemented by knowledgeable people. On
      the other hand, the life cycle can be controlled by avoiding swine cysticercosis.
      This review describes the studies performed to vaccinate pigs against T. solium
      and indicate that short time perspectives are very encouraging for the production
      of an optimal vaccine.

PMID- 11313645
TI  - Chromosomal comparisons among and within populations of Simulium (Chirostilbia)
      pertinax (Diptera, Simuliidae).
AB  - Chromosomal studies were carried on six larval populations of Simulium
      (Chirostilbia) pertinax from different locations in Brazil. Larvae were collected
      in the states of Parana, Rio Grande do Sul, Rio de Janeiro and Sao Paulo.
      Polytene chromosome map comparisons within and among populations showed no
      differences in banding pattern, except for some limited polymorphism (secondary
      NOR and four band polymorphisms). There were no chromosomal variations associated
      with the resistance or susceptibility of the larvae to temephos. The chromosomal
      homosequentiality found among the six populations suggests that S. pertinax may
      be a monomorphic species.

PMID- 11313646
TI  - C-banding and FISH in chromosomes of the blow flies Chrysomya megacephala and
      Chrysomya putoria (Diptera, Calliphoridae).
AB  - The blow flies Chrysomya putoria and C. megacephala have 2n=12 chromosomes, five
      metacentric pairs of autosomes and an XX/XY sex chromosome pair. There are no
      substantial differences in the karyotype morphology of these two species, except
      for the X chromosome which is subtelocentric in C. megacephala and metacentric in
      C. putoria and is about 1.4 times longer in C. putoria. All autosomes were
      characterized by the presence of a C band in the pericentromeric region; C.
      putoria also has an interstitial band in pair III. The sex chromosomes of both
      species were heterochromatic, except for a small region at the end of the long
      arm of the X chromosome. Ribosomal genes were detected in meiotic chromosomes by
      FISH and in both species the NOR was located on the sex chromosomes. These
      results confirm that C. putoria was the species introduced into Brazil in 1970s,
      and not C. chloropyga as formerly described.

PMID- 11313647
TI  - Brain cell karyotype of the phlebotomine sand fly Lutzomyia shannoni (Dyar)
      (Diptera: Psychodidae).
AB  - The brain cell karyotype of New World sand fly Lutzomyia shannoni was described.
      This species has four pairs of chromosomes, 2N=8, with one pair of heteromorphic
      chromosomes.

PMID- 11313648
TI  - Resistance of Biomphalaria occidentalis from Varzea das Flores dam, Minas Gerais,
      to Schistosoma mansoni infection detected by low stringency polymerase chain
      reaction.
AB  - Biomphalaria occidentalis Paraense, 1981 from Varzea das Flores dam, MG, Brazil,
      was exposed to infection with Schistosoma mansoni. Individual infection was
      performed with 140 B. occidentalis and 100 B. glabrata snails using LE and SJ
      strains. Two groups of B. occidentalis were killed after seven day-miracidia
      exposure to detect S. mansoni DNA, through the low stringency polymerase chain
      reaction (LS-PCR), and were negative. The infection rates were 69.2% (LE strain)
      and 96.7% (SJ strain) for B. glabrata and 0% for B. occidentalis. LS-PCR enabled
      early resistance diagnosis.

PMID- 11313649
TI  - Flight and nutritional status of sylvatic Triatoma sordida and Triatoma
      guasayana.
AB  - Nutritional status relating to flight activity was investigated in natural
      populations of Triatoma sordida and T. guasayana during the dry season in the
      Bolivian Chaco. The peak flight activity of both species was unimodal and covered
      the period 61-180 min after sunset. The weight of insects was used as the
      indicator of nutritional status. Interspecies comparisons employing the same sex
      and type of capture showed a higher weight for T. guasayana. No significant
      difference according to weight was observed between flying insects and those
      collected in natural ecotopes (hollow trees and bromeliads). More than 87% of
      insects collected from natural ecotopes displayed flight ability under the study
      conditions, explaining their tendency to invade artificial structures during the
      dry season.

PMID- 11313650
TI  - Anesthesia of Biomphalaria spp. (Mollusca, Gastropoda): sodium pentobarbital is
      the drug of choice.
AB  - The anesthetic effect of some water-soluble anesthesic or narcotic drugs
      currently used in mice was tested in molluscs of the Biomphalaria genus. Sodium
      thiopental was very toxic to the snails resulting in high rates of mortality in
      all the treatment schedules tested. Cetamine base, at concentration of 0.25 mg/ml
      of water, resulted in partial snail anesthesia (40% of snails were anesthetized)
      only after 20 h of exposition. The association of Cetamine base with Tiazine
      chloridrate did not improve the anesthesic effect, and higher concentrations of
      these drugs were toxic to the snails. Sodium pentobarbital at 0.4 mg/ml in water
      for 8 h was the best treatment schedule to anesthetize Biomphalaria snails. In
      this schedule, the snails were anesthetized without any toxic effect. The
      procedure provides a powerful tool for in vivo studies that demande a complete
      state of snail anesthesia.

PMID- 11313651
TI  - Lower faecal egg excretion in chemically-induced diabetic mice infected with
      Schistosoma mansoni due to impaired egg maturation.
AB  - The effect of streptozotocin-induced diabetes mellitus was studied in mice
      infected with Schistosoma mansoni. Faecal egg excretion was lower in diabetic
      mice but worm load and total amount of eggs in the intestine tissue were equal to
      the control group. Evaluation of an oogram showed a great number of immature dead
      eggs and a low number of mature eggs in diabetic mice. It was therefore concluded
      that faecal egg excretion was lower in diabetic mice due to impaired egg
      maturation.

PMID- 11313652
TI  - Phylogeny of the kinetoplastida: taxonomic problems and insights into the
      evolution of parasitism.
AB  - To further investigate phylogeny of kinetoplastid protozoa, the sequences of
      small subunit (18S) ribosomal RNA of nine bodonid isolates and ten isolates of
      insect trypanosomatids have been determined. The root of the kinetoplastid tree
      was attached to the branch of Bodo designis and/or Cruzella marina. The suborder
      Trypanosomatina appeared as a monophyletic group, while the suborder Bodonina was
      paraphyletic. Among bodonid lineages, parasitic organisms were intermingled with
      free-living ones, implying multiple transitions to parasitism and supporting the
      'vertebrate-first hypothesis'. The tree indicated that the genera Cryptobia and
      Bodo are artificial taxa. Separation of fish cryptobias and Trypanoplasma borreli
      as different genera was not supported. In trypanosomatids, the genera Leptomonas
      and Blastocrithidia were polyphyletic, similar to the genera Herpetomonas and
      Crithidia and in contrast to the monophyletic genera Trypanosoma and Phytomonas.
      This analysis has shown that the morphological classification of kinetoplastids
      does not in general reflect their genetic affinities and needs a revision.

PMID- 11313653
TI  - Courtship song genes and speciation in sand flies.
AB  - Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae)
      is a vector of visceral leishmaniasis in the Americas and it might represent a
      complex of sibling species. Reproductive isolation between closely related
      species often involves differences in courtship behaviour. cacophony (cac) and
      period (per) are two Drosophila genes that control features of the "lovesong"
      males produce during courtship that has been implicated in the sexual isolation
      between closely related species. We are using gene fragments from L. longipalpis'
      homologues of these two genes to study the speciation process in this putative
      species complex.

PMID- 11313654
TI  - Usefulness of microsatellite typing in population genetic studies of Trypanosoma
      cruzi.
AB  - Through microsatellite analysis of 53 monoclonal populations of Trypanosoma
      cruzi, we found a remarkable degree of genetic polymorphism with no single
      multilocus genotype being observed more than once. The microsatellite profile
      proved to be stable during 70 generations of the CL Brener clone in culture. The
      microsatellite profiling presented also high diagnostic sensitivity since DNA
      amplifications could be achieved with less than 100 fg DNA, corresponding to half
      parasite total DNA content. Based on these technical attributes the
      microsatellite assay turns out to be an important tool for direct typing T. cruzi
      in biological samples. By using this approach we were able to type T. cruzi in
      feces of artificially infected bugs and in single cells sorted by FACS. The
      microsatellites have shown to be excellent markers for T. cruzi phylogenetic
      reconstruction. We used maximum parsimony based on the minimum number of
      mutational steps to build an unrooted Wagner network, which confirms previous
      conclusions based on the analysis of the D7 domain of the LSU rDNA gene that T.
      cruzi is composed by two major groups. We also obtained evidence that strains
      belonging to rRNA group 2 are subdivided into two genetically distant clusters,
      and that one of these clusters is more related to rRNA group (1/2). These results
      suggest different origins for these strains.

PMID- 11313655
TI  - Coevolutionary networks: a novel approach to understanding the relationships of
      humans with the infectious agents.
AB  - Human organism is interpenetrated by the world of microorganisms, from the
      conception until the death. This interpenetration involves different levels of
      interactions between the partners including trophic exchanges, bi-directional
      cell signaling and gene activation, besides genetic and epigenetic phenomena, and
      tends towards mutual adaptation and coevolution. Since these processes are
      critical for the survival of individuals and species, they rely on the existence
      of a complex organization of adaptive systems aiming at two apparently
      conflicting purposes: the maintenance of the internal coherence of each partner,
      and a mutually advantageous coexistence and progressive adaptation between them.
      Humans possess three adaptive systems: the nervous, the endocrine and the immune
      system, each internally organized into subsystems functionally connected by
      intraconnections, to maintain the internal coherence of the system. The three
      adaptive systems aim at the maintenance of the internal coherence of the organism
      and are functionally linked by interconnections, in such way that what happens to
      one is immediately sensed by the others. The different communities of infectious
      agents that live within the organism are also organized into functional networks.
      The members of each community are linked by intraconnections, represented by the
      mutual trophic, metabolic and other influences, while the different infectious
      communities affect each other through interconnections. Furthermore, by means of
      its adaptive systems, the organism influences and is influenced by the microbial
      communities through the existence of transconnections. It is proposed that these
      highly complex and dynamic networks, involving gene exchange and epigenetic
      phenomena, represent major coevolutionary forces for humans and microorganisms.

PMID- 11313656
TI  - Genome comparison of progressively drug resistant Plasmodium falciparum lines
      derived from drug sensitive clone.
AB  - Chloroquine has been the mainstay of malaria chemotherapy for the past five
      decades, but resistance is now widespread. Pyrimethamine or proguanil form an
      important component of some alternate drug combinations being used for treatment
      of uncomplicated Plasmodium falciparum infections in areas of chloroquine
      resistance. Both pyrimethamine and proguanil are dihydrofolate reductase (DHFR)
      inhibitors, the proguanil acting primarily through its major metabolite
      cycloguanil. Resistance to these drugs arises due to specific point mutations in
      the dhfr gene. Cross resistance between cycloguanil and pyrimethamine is not
      absolute. It is, therefore, important to investigate mutation rates in P.
      falciparum for pyrimethamine and proguanil so that DHFR inhibitor with less
      mutation rate is favored in drug combinations. Hence, we have compared mutation
      rates in P. falciparum genome for pyrimethamine and cycloguanil. Using
      erythrocytic stages of P. falciparum cultures, progressively drug resistant lines
      were selected in vitro and comparing their RFLP profile with a repeat sequence.
      Our finding suggests that pyrimethamine has higher mutation rate compared to
      cycloguanil. It enhances the degree of genomic polymorphism leading to diversity
      of natural parasite population which in turn is predisposes the parasites for
      faster selection of resistance to some other antimalarial drugs.

PMID- 11313657
TI  - Genetic markers from Biomphalaria tenagophila (Gastropoda: Pulmonata:
      Planorbidae) obtained by the double stringency polymerase chain reaction
      technique.
AB  - Biomphalaria tenagophila, one of the intermediate hosts of the trematoda
      Schistosoma mansoni, is a simultaneous hermafrodite snail species. In order to
      analyse the genetic structure of these populations, we performed a double
      stringency PCR technique to obtain genetic markers with microsatellites and
      arbitrary primers in a single reaction.

PMID- 11313658
TI  - Relationship between the recurrent laryngeal nerve and the inferior thyroid
      artery: a study in corpses.
AB  - The anatomical relationship between the recurrent laryngeal nerve (RLN) and the
      inferior thyroid artery (ITA) was studied in 76 embalmed corpses, 8 females and
      68 males. In both sexes, the RLN lay more frequently between branches of the
      ITA.; it was found in this position in 47.3% of male corpses and 42.8% of female
      ones. On the right, RLN was found between branches of the ITA in 49.3% of the
      cases, anterior to it in 38.04%, and posterior in 11.26%. On the left, the RLN
      lay between branches of the ITA in 44.45%, posterior to the ITA in 37.05%, and
      anterior to it in 18.05% of the cases. In 62.68% of the cases, the relationship
      found on one side did not occur again on the opposite side. There was a
      significant difference (p<0.05) in the distribution of the 3 types of
      relationships between the RLN and the ITA, on the right and on the left. Racial
      variations could contribute to an explanation of the differences observed by
      authors of different countries in the relationship between the RLN and the ITA.

PMID- 11313659
TI  - Ursodeoxycholic acid does not interfere with in vivo Helicobacter pylori
      colonization.
AB  - A low frequency of Helicobacter pylori in the gastric mucosa of patients with
      alkaline gastritis has been reported. At the same time, it can be noted that the
      growth of bacteria can be inhibited by bile acids. We studied 40 patients with
      chronic gastritis related to Helicobacter pylori in order to determine the effect
      of ursodeoxycholic acid on this infection. Diagnoses of the infection and the
      inflammatory process were obtained by histologic study of gastric biopsies
      collected during endoscopy. Two groups were studied: group I received
      ursodeoxycholic acid - 300 mg/day, and group II received the placebo, twice a
      day, both for 28 days. The colonization by Helicobacter pylori and the intensity
      of the mononuclear and polymorphonuclear inflammatory infiltrate were determined
      before (time 1) and after (time 2) treatment. Ursodeoxycholic acid had no effect
      on the Helicobacter pylori infection. A significant reduction in the intensity of
      the mononuclear inflammatory infiltrate of the gastric antrum mucosa was observed
      in patients from group I, when we compared not only times 1 and 2 but also groups
      I and II. However, this was not the case with the body mucosa. We concluded that
      ursodeoxycholic acid had no action on the colonization by Helicobacter pylori or
      on the polymorphonuclear inflammatory infiltrate, but it caused a significant
      reduction in the intensity of the mononuclear inflammatory infiltrate of the
      gastric antrum.

PMID- 11313660
TI  - Comparison of the fluorescent polarization (TDx) and the enzymatic competitive
      (EMIT 2000) immune assays for the measurement of cyclosporin A blood
      concentration.
AB  - Evaluation of Cyclosporin A (CyA) blood concentration is imperative in solid
      organ transplantation in order to achieve maximal immunosuppression with the
      least side effects. We compared the results of whole blood concentrations of CyA
      in 50 blood samples simultaneously evaluated by the fluorescent polarization
      immune assay (TDx) and the enzymatic competitive immune assay (EMIT 2000). There
      was a strong correlation between both kits for any range of CyA blood
      concentration (R=0.99, p<0.001). The within-run and between-days coefficient of
      variation were less than 4% for both assays. The cost for each CyA measurement
      was 50% lower for the EMIT assay when compared to the TDx assay. We concluded
      that the EMIT is as accurate as the TDx in measuring CyA blood concentration and
      has the advantage of a lower cost, as well as the possibility of widespread
      access to the EMIT methodology in contrast to the TDx equipment, allowing the
      laboratory to perform several routines within a working day.

PMID- 11313661
TI  - Clinical and laboratorial study of 19 cases of mucopolysaccharidoses.
AB  - The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of
      lysosomal glycosaminoglycan (GAG) metabolism. The importance of this group of
      disorders among the inborn errors of metabolism led us to report 19 cases.
      METHOD: We performed clinical, radiological, and biochemical evaluations of the
      suspected patients, which allowed us to establish a definite diagnosis in 19
      cases. RESULTS: Not all patients showed increased GAG levels in urine; enzyme
      assays should be performed in all cases with strong clinical suspicion. The
      diagnosis was made on average at the age of 48 months, and the 19 MPS cases,
      after a full clinical, radiological, and biochemical study, were classified as
      follows: Hurler - MPS I (1 case); Hunter - MPS II (2 cases); Sanfilippo - MPS III
      (2 cases); Morquio - MPS IV (4 cases); Maroteaux-Lamy - MPS VI (9 cases); and Sly
      - MPS VII (1 case). DISCUSSION: The high relative frequency of Maroteaux-Lamy
      disease contrasts with most reports in the literature and could express a
      population variability.

PMID- 11313662
TI  - Intestinal intussusception and occlusion caused by small bowel polyps in the
      Peutz-Jeghers syndrome. Management by combined intraoperative enteroscopy and
      resection through minimal enterostomy: case report.
AB  - The Peutz-Jeghers syndrome is a hereditary disease that requires frequent
      endoscopic and surgical intervention, leading to secondary complications such as
      short bowel syndrome. CASE REPORT: This paper reports on a 15-year-old male
      patient with a family history of the disease, who underwent surgery for treatment
      of an intestinal occlusion due to a small intestine intussusception. DISCUSSION:
      An intra-operative fiberscopic procedure was included for the detection and
      treatment of numerous polyps distributed along the small intestine. Enterotomy
      was performed to treat only the larger polyps, therefore limiting the intestinal
      resection to smaller segments. The postoperative follow-up was uneventful.
      CONCLUSION: We point out the importance of conservative treatment for patients
      with this syndrome, especially those who will undergo repeated surgical
      interventions because of clinical manifestation while they are still young.

PMID- 11313663
TI  - Comparison of total body irradiation vs busulfan in combination with
      cyclophosphamide as conditioning for unrelated stem cell transplantation in CML
      patients.
AB  - We compared fractionated total body irradiation (12 Gy)/cyclophosphamide (120
      mg/kg) with busulfan (16 mg/kg)/cyclophosphamide (120 mg/kg) as preparative
      therapy in unrelated donor stem cell transplantation of CML patients. Fifty
      patients with CML (1.CP = 46; aP = 4) and a median age of 36 years (range 16-52)
      were enrolled in this sequential trial between 1994 and 1999. In both groups
      patients were well balanced with respect to age, disease status, stem cell source
      and CMV status. All patients received standard doses of cyclosporin A,
      methotrexate and anti-thymocyte globulin (ATG) as GVHD prophylaxis. No graft
      failures occurred in either group. The median day of leukocyte engraftment was
      earlier in the Bu/Cy than in the TBI/Cy group (day 15 vs 17; P = 0.006). The
      incidence of grade II-IV GVHD was 40% in the TBI/Cy and 36% in the Bu/Cy group,
      whereas severe grade III/IV GVHD was only observed in 12% of patients in both
      groups. The incidence of chronic GVHD (limited and extensive) at 1 year was
      higher in the Bu/Cy arm (65% vs 30%; P = 0.02). More toxicity grade I/II of the
      liver (88% vs 44%; P = 0.002) and more hemorrhagic cystitis (32% vs 8%; P = 0.02)
      were observed in the Bu/Cy regimen. Seven relapses in the TBI and no relapse in
      the Bu/Cy group were observed after a median follow-up of 44 and 15 months,
      respectively. The estimated 3 year OS and DFS was 72% (95% CI: 55-98%) and 58%
      (95% CI: 39-77%) in the TBI and 70% (95% CI: 51-89%) for DFS and OS in the Bu/Cy
      group. We conclude that the anti-leukemic effect of the Bu/Cy regimen seems to be
      at least as effective as the TBI/Cy combination in unrelated stem cell
      transplantation of CML patients, with no graft failures, but that it correlates
      with a higher incidence of liver toxicity, hemorrhagic cystitis and chronic GVHD.
      Longer follow-up is necessary to determine the late relapse rate and late
      toxicity.

PMID- 11313664
TI  - Transplantation of a fetus with paternal Thy-1(+)CD34(+)cells for chronic
      granulomatous disease.
AB  - A fetus diagnosed with X-linked chronic granulomatous disease was transplanted
      with Thy-1(+)CD34(+) cells of paternal origin. The transplant was performed at 14
      weeks gestation by ultrasound guided injection into the peritoneal cavity. The
      fetus was delivered at 38 weeks gestation after an otherwise uneventful
      pregnancy. Umbilical cord blood was collected and used to determine the level of
      peripheral blood chimerism as well as levels of functional engrafted cells. Flow
      cytometry was used to detect donor leukocytes identified as HLA-A2(-)B7(+) cells,
      whereas recipient cells were identified as HLA-A2(+)B7(-) cells. No evidence of
      donor cell engraftment above a level of 0.01% was found. PCR was used to detect
      HLA-DRB1*15(+) donor cells among the recipient's HLA-DRB1*15(-) cells, but no
      engraftment was seen with a sensitivity of 1:1000. The presence of functional,
      donor-derived neutrophils was assessed by flow cytometry using two different
      fluorescent dyes that measure reactive oxygen species generated by the phagocyte
      NADPH oxidase. No evidence of paternal-derived functional neutrophils above a
      level of 0.15% was observed. Peripheral blood and bone marrow samples were
      collected at 6 months of age. Neither sample showed engraftment by HLA typing
      using both flow cytometry and PCR. Functional phagocytes were also not observed.
      Furthermore, no indication of immunological tolerance specific for the donor
      cells was indicated by a mixed lymphocyte reaction assay performed at 6 months of
      age. While there appears to be no engraftment of the donor stem cells, the
      transplant caused no harm to the fetus and the child was healthy at 6 months of
      age. Analyses of fetal tissues, obtained from elective abortions, revealed that
      CD3(+) T cells and CD56(+)CD3(-) NK cells are present in the liver at 8 weeks
      gestation and in the blood by 9 weeks gestation. The presence of these
      lymphocytes may contribute to the lack of donor cell engraftment in the human
      fetus.

PMID- 11313665
TI  - The CD34(+)CD38(neg) population is significantly increased in haemopoietic cell
      expansion cultures in serum-free compared to serum-replete conditions:
      dissociation of phenotype and function.
AB  - Expansion of haemopoietic stem cells is proposed to combat graft failure in adult
      recipients following cord blood (CB) transplantation. Cultures are traditionally
      performed in medium containing FCS, but to transfer expansion to the clinic,
      'good manufacturing practice' (GMP) standards are required. This study evaluated
      expansion cultures in culture bags and serum-free (SF) conditions, to comply with
      GMP, by analysing sub-populations of CD34(+) cells, colony-forming cells (CFC)
      and long-term culture initiating cells (LTC-IC). CD34(+)cell analysis has
      previously been used to measure clonogenic capacity and the CD34(+)CD38(neg)
      surface phenotype to measure primitive cell numbers. In this study, comparison of
      expansion in serum-replete medium with that in SF conditions demonstrated a lack
      of expression of CD38 on CD34(+) cells in the absence of serum. These findings
      must be considered in clinical studies using in vitro expansion in SF conditions,
      and the CD34(+)CD38(neg) phenotype should not be used to confirm maintenance, or
      expansion, of primitive progenitor cells.

PMID- 11313666
TI  - Kinetic analysis of cytokine gene expression in patients with GVHD after donor
      lymphocyte infusion.
AB  - Patients who receive a donor lymphocyte infusion (DLI) for the treatment of
      relapsed leukemia after allogeneic BMT (alloBMT) often developed GVHD. To
      determine whether cytokines might have a role in GVHD, an intensive kinetic
      analysis of in vivo cytokine gene expression was performed on PBMC from three
      such patients. Expression of IL-1beta, IL-2, IFN-gamma, IL-4, IL-5, IL-8, IL-10,
      IL-12, TNF-alpha, and IL-2Ralpha was examined using a sensitive semi-quantitative
      reverse transcription (RT)-PCR assay system. Six normal controls were also
      analyzed for comparison. Expression of type 1 T helper (Th1) cytokines, IL-2 and
      IFN-gamma was greatly increased in all three patients. In particular, the changes
      in IL-2 gene expression correlated well with disease progression, suggesting that
      IL-2 has a critical role in the development of GVHD. Although the pattern of type
      2 T helper (Th2) cytokine gene expression differed in each patient, the
      expression of IL-4 was inversely related to expression of Th1 cytokines. These
      results suggest that Th1 dominates in the development of human clinical GVHD.

PMID- 11313667
TI  - Hematopoietic stem cell transplantation for Diamond Blackfan anemia: a report
      from the Diamond Blackfan Anemia Registry.
AB  - The Diamond Blackfan Anemia (DBA) Registry of North America is a detailed
      database of patients with DBA from the United States and Canada. To date, 354
      patients have been registered. From this database an analysis of the outcome of
      hematopoietic stem cell transplantation for DBA was undertaken. Of the 20
      transplanted patients who met criteria for the diagnosis of DBA, eight underwent
      an allogeneic HLA-matched sibling hematopoietic stem cell transplant (SCT) and 12
      an alternative donor SCT. The median age at transplant for all patients was 6
      years 2 months; 3 years 10 months vs 9 years 1 month for HLA-matched sibling and
      alternative donor SCT, respectively. All of the HLA-matched sibling transplants
      were done using a non-irradiation-containing regimen, whereas the majority of
      alternative donor transplants were performed using total body irradiation. The
      survival for HLA-matched sibling vsalternative donor transplant was 87.5% +/-
      11.7% vs 14.1% +/- 12.1% at greater than 5 years from SCT (P = 0.015). The use of
      HLA-matched sibling SCT should be considered for all patients with suitable
      donors. However, alternative donor SCT in DBA must be approached cautiously, the
      potential for severe aplastic anemia (SAA) or hematopoietic malignancy not
      withstanding.

PMID- 11313668
TI  - Autotransplants for Hodgkin's disease in first relapse or second remission: a
      report from the autologous blood and marrow transplant registry (ABMTR).
AB  - Although patients with relapsed Hodgkin's disease have a poor prognosis with
      conventional therapies, high-dose chemotherapy and autologous hematopoietic stem
      cell transplantation (autotransplantation) may provide long-term progression-free
      survival. We reviewed data from the Autologous Blood and Marrow Transplant
      Registry (ABMTR) to determine relapse, disease-free survival, overall survival,
      and prognostic factors in this group of patients. Detailed records from the ABMTR
      on 414 patients with Hodgkin's disease in first relapse (n = 295) or second
      complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995
      were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis
      to relapse was 18 (range, 6-219) months; median time from relapse to transplant
      was 5 (range, <1-215) months. Most patients received high-dose chemotherapy
      without total body irradiation for conditioning (n = 370). The most frequently
      used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The
      graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n
      = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality
      (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295
      patients (56%) transplanted in relapse achieved CR after autotransplantation. Of
      these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR
      recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for
      transplants in first relapse and 64 (53-72)% for those in second remission (P <
      0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in
      first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In
      multivariate analysis, Karnofsky performance score <90% at transplant, abnormal
      serum LDH at transplant, and chemotherapy resistance were adverse prognostic
      factors for outcome. Progression of Hodgkin's disease accounted for 69% of all
      deaths. Autotransplantation should be considered for patients with Hodgkin's
      disease in first relapse or second remission. Future investigations should focus
      on strategies designed to decrease relapse after autotransplantation,
      particularly in patients at high risk for relapse.

PMID- 11313669
TI  - Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth
      factor rescue in recurrent aggressive NHL. High response rates and limited
      toxicity, but limited impact on long-term survival.
AB  - The purpose of the study was to evaluate in patients with recurrent intermediate
      grade NHL, the tolerance to and efficacy of an intensive salvage regimen
      consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF
      support, followed by autologous stem cell transplantation and to identify
      prognostic factors for survival in patients with recurrent aggressive lymphoma.
      Patients with recurrent intermediate-grade NHL under the age of 60 years were
      eligible. Induction consisted of ifosfamide 10 g/m(2) and etoposide 900 mg/m(2)
      with G-CSF 5 microg/kg twice a day. Upon recovery, patients underwent stem cell
      apheresis. Patients achieving complete remission (CR) underwent autologous stem
      cell transplantation using BEAM conditioning. Those with partial remission (PR)
      received treatment with ifosfamide 10 g/m(2), mitoxantrone 20 mg/m(2) and G-CSF 5
      microg/kg. Those with CR received BEAM, those with PR received cyclophosphamide
      4.5 g/m(2), etoposide 1200 mg/m(2) and cisplatin 135 mg/m(2) with stem cell
      rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment
      cycles. The results were compared with those obtained in a prior study that used
      MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL
      were enrolled between March 1994 and September 1996. Median age was 50 years (24
      61). Eleven patients had transformed lymphoma and seven had a T cell phenotype.
      Response rate to the high-dose ifosfamide regimen was 77% +/- 12% after two
      cycles and the complete response rate was 41% +/- 14%. Myelosuppression was
      profound but short. Median nadir ANC was 0 and the median duration of ANC <0.5 x
      10(9)/l was 6 days (range 3-12). No severe infections occurred; 55% of the
      patients required blood transfusion and 42% required platelet transfusions.
      Myelosuppression and transfusion requirements were similar after the first and
      second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell
      transplantation and one transplant-related death occurred. With a median follow
      up of 52 months, progression-free survival at 2 years is 38% +/- 14% and survival
      is 52% +/- 15%. Data from these 44 patients were pooled with data on 53 patients
      who had received salvage treatment with MINE-ESHAP, for a multivariate analysis
      of prognostic factors. In multivariate analysis, serum LDH was strongly
      associated with survival. The use of a more intensive salvage regimen, did not
      result in a significant increase in long-term outcome, despite a high response
      rate. In conclusion, duration of treatment, response rates, treatment-related
      mortality and survival compare favorably with previous salvage regimens, but
      recurrence remains a major problem. Long-term survival in recurrent large cell
      lymphoma is influenced more by disease characteristics than by the type of
      salvage regimen used.

PMID- 11313670
TI  - Autologous stem cell transplantation for clinically aggressive non-Hodgkin's
      lymphoma: the role of preparative regimens.
AB  - We investigated the impact of the most commonly used preparative regimens on the
      outcome of 395 patients with diffuse large cell lymphoma (DLCL), consecutively
      reported to the registry of the Spanish GEL/TAMO. Among them, 139 (35%) were
      autografted in 1st CR, 86 (22%) in 2nd/3rd CR, 124 (31%) had chemosensitive
      disease and 46 (12%) had chemoresistant disease. Conditioning consisted of
      chemotherapy-only in 348 patients (BEAM, 164; BEAC, 145; and CBV, 39) and
      radiochemotherapy with CY and TBI in 47. Median times to granulocyte, platelet
      recovery and to discharge were significantly shorter in the chemotherapy-only
      group. Early transplant-related mortality was significantly higher when using CY
      TBI. After a median follow-up of 28 months, overall survival (OS) at 8 years of
      patients conditioned with BEAM or BEAC (58% (95% CI 50-66%)) was more favorable
      than with CBV (40% (95% CI 24-56%)), and significantly better than with CY-TBI
      (31% (95% CI 18-44%)). Multivariate analysis revealed that patients conditioned
      with chemotherapy-only regimens had improved OS, disease-free (DFS) and relapse
      free survival (RFS) when compared to those conditioned with CY-TBI. Status at
      transplant was also a powerful prognostic indicator. We conclude that preparative
      regimens consisting of chemotherapy-only seem more efficacious than CY-TBI as
      conditioning for DLCL, because of faster engraftment and greater anti-lymphoma
      effect, as indicated by improved OS, DFS and RFS.

PMID- 11313671
TI  - Ig heavy chain CDR3 size diversities are similar after conventional peripheral
      blood and ex vivo expanded hematopoietic cell transplants.
AB  - It is largely unknown whether the immune repertoire can be reconstituted
      successfully after high-dose chemotherapy and transplantation using ex vivo
      expanded hematopoietic stem cell (HSC) grafts. It is critically important for the
      transplant outcome that immune repertoire reconstitution progresses after ex vivo
      expanded HSC graft transplants at least as efficiently as that seen after
      conventional HSC transplants. Previously, we showed that the T cell receptor V
      beta (TCRVB) third complementarity determining region (CDR3) diversification
      after ex vivo expanded bone marrow (BM) HSC graft transplants was similar to that
      seen after conventional peripheral blood stem cell transplants (PBSCTs). In the
      present study, the CDR3 diversity of the six immunoglobulin (Ig) heavy chain
      variable region gene (V(H)) families was examined in five breast cancer patients
      who were transplanted with ex vivo expanded BM HSCs as the only source of stem
      cells. For comparison, 12 healthy adults and four conventional PBSCT recipients
      were also studied. Using both CDR3 fingerprinting and single strand conformation
      polymorphism (SSCP) methodologies, it is shown that the contribution of the V(H)
      families to the overall repertoire among healthy adults is highly variable and
      not always proportional to V(H) family member size. After both ex vivo expanded
      HSC transplants and conventional PBSCTs, the V(H) CDR3 repertoires were limited
      in size diversity at 6 weeks post transplant. By 6 months, however, V(H) families
      displayed a repertoire diversity that was as complex as that seen in healthy
      adults. No difference was seen between ex vivo expanded HSC graft transplant
      recipients and conventional PBSCT recipients in V(H) repertoire diversity. In one
      patient there was a follow-up analysis 12 months after ex vivo expanded graft
      transplant, and the diversity of the V(H) families was maintained. In all
      patients, the amino acid size of the CDR3 regions fell within adult limits at all
      time points post transplant. These results indicate that B cell repertoire
      regeneration after ex vivo expanded hematopoietic cell graft transplants is
      similar to that seen after conventional PBSCT.

PMID- 11313672
TI  - Reconstitution of the CD45RO(+) and CD20(+) lymphoid marrow population following
      allogeneic bone marrow transplantation for Ph(+) CML.
AB  - Following bone marrow transplantation (BMT) investigations on the recovery of the
      B and T lymphocyte populations have focused on the peripheral blood and only
      marginally regard the bone marrow. An immunohistochemical and morphometric study
      was performed on 352 trephine biopsies derived from 123 patients with chronic
      myelogenous leukemia (CML) at standardized endpoints before and after allogeneic
      BMT and compared to a control group. The purpose of this investigation was to
      quantify the B-CD20(+) and T-CD45RO(+) lymphocyte subsets and to determine
      possible relationships with the occurrence of acute and chronic GVHD. Moreover,
      we studied the dynamics of lymphocyte repopulation in the post-transplant period,
      correlations with the total peripheral lymphocyte count and differences
      associated with sibling vs alternate HLA-compatible (unmanipulated) marrow
      grafts. Morphometric analysis revealed a very fast regeneration of CD45RO(+) and
      CD20(+) marrow lymphocytes in the first 2 weeks following BMT. In less than 2
      months, in most patients, the post-transplant quantity of lymphocytes was
      comparable to that of the normal bone marrow. This finding was opposed to the
      profound depression of the absolute lymphocyte count in the peripheral blood. No
      relevant relationships could be calculated between engraftment status and the
      lymphocyte repopulation in the bone marrow. On the other hand, significant
      correlations were calculable between the development of (chronic and acute) GVHD
      including severity with the number of CD45RO(+) lymphocytes. In non-related graft
      constellations a more frequent evolution of acute grade III + IV GVHD was
      detectable. This complication was accompanied by an increased quantity of
      CD45RO(+) lymphocytes in the marrow.

PMID- 11313674
TI  - Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV
      antigenemia assay after allogeneic hematopoietic stem cell transplantation: a
      single-center experience in Japan.
AB  - From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre
      emptive approach for CMV disease was evaluated in 77 adult patients who received
      allogeneic hematopoietic stem cell transplantation at the National Cancer Center
      Hospital. A CMV antigenemia assay was performed at least once a week after
      engraftment. High-level antigenemia was defined as a positive result with 10 or
      more positive cells per 50 000 cells and low-level antigenemia was defined as
      less than 10 positive cells. Among the 74 patients with initial engraftment, 51
      developed positive antigenemia. Transplantation from alternative donors and the
      development of grade II-IV GVHD were independent risk factors for positive
      antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients
      in a risk-adapted manner. None of the nine low-risk patients with low-level
      antigenemia as their initial positive result developed high-level antigenemia
      even though ganciclovir was withheld. Only one patient developed early CMV
      disease (hepatitis) during the study period. CMV antigenemia resolved in all but
      two cases, in whom ganciclovir was replaced with foscarnet. In eight patients,
      however, the neutrophil count decreased to 0.5 x 10(9)/l or less after starting
      ganciclovir, including three with documented infections and two with subsequent
      secondary graft failure. The total amount of ganciclovir and possibly the
      duration of high-dose ganciclovir might affect the incidence of neutropenia. We
      concluded that antigenemia-guided pre-emptive therapy with a decreased dose of
      ganciclovir and response-oriented dose adjustment might be appropriate to
      decrease the toxicity of ganciclovir without increasing the risk of CMV disease.

PMID- 11313673
TI  - A possible role for lamivudine as prophylaxis against hepatitis B reactivation in
      carriers of hepatitis B who undergo chemotherapy and autologous peripheral blood
      stem cell transplantation for non-Hodgkin's lymphoma.
AB  - Hepatitis B virus (HBV) reactivation, a well-known complication in
      immunosuppressed patients, can give rise to acute hepatitis and even fatal
      fulminant hepatitis. Three Japanese males with non-Hodgkin's lymphoma (NHL) who
      were carriers of HBV received high-dose chemotherapy followed by autologous
      peripheral blood stem cell transplantation (PBSCT). To prevent HBV reactivation,
      all received oral lamivudine (150 mg/day), a nucleoside analogue, at the start of
      chemotherapy. All were treated at full-dose intensity, including corticosteroids,
      without modification of treatment regimens. All three patients completed the
      total course of chemotherapy and PBSCT, with no signs of HBV reactivation.
      Peripheral blood stem cell (PBSC) harvests and hematological recoveries after
      transplantation were not affected by lamivudine, which was continued for at least
      16 weeks after transplantation. HBV-DNA and DNA polymerase levels remained
      negative/normal after discontinuation of lamivudine. Lamivudine effectively
      inhibits HBV replication and has few serious adverse effects, particularly those
      related to hematopoiesis. Thus, prophylactic use of lamivudine from initiation of
      chemotherapy deserves consideration in the treatment of HBV carriers who require
      immunosuppressive chemotherapy, and may prevent HBV reactivation.

PMID- 11313675
TI  - Corynebacterium jeikeium bacteremia in bone marrow transplant patients with
      Hickman catheters.
AB  - Prior studies suggest that Corynebacterium jeikeium bacteremia in
      immunocompromised patients results in frequent morbidity that may be decreased by
      prompt removal of the indwelling catheter. To summarize recent experience, charts
      of 53 bone marrow transplant recipients with Hickman catheters and C. jeikeium
      bacteremia were reviewed. Forty-one patients were treated with vancomycin without
      catheter removal and 10 patients underwent catheter removal with subsequent
      vancomycin therapy. No patient in either group died with C. jeikeium bacteremia
      as the proximate cause. Salvage of the intravascular catheter was successful in
      38 of 41 (93%) attempts. Three patients (7%) in the catheter-salvage group and
      one patient (10%) in the catheter-removal group experienced recurrent bacteremia.
      In both catheter-salvage and catheter-removal groups, median time to negative
      blood culture was 2 days. Thus, time to clearance of bacteremia and patient
      clinical outcome did not differ between treatment groups. In many patients with
      Hickman catheters, C. jeikeium bacteremia may be treated successfully with
      vancomycin and without removal of the catheter.

PMID- 11313676
TI  - Loss of renal function following bone marrow transplantation: an analysis of
      angiotensin converting enzyme D/I polymorphism and other clinical risk factors.
AB  - Chronic renal failure is an acknowledged late complication of BMT. It is related
      to the intensive chemotherapy, radiation and supporting medications. Polymorphism
      in the angiotensin converting enzyme (ACE) gene is associated with progression of
      nephropathy caused by diabetes and IgA nephropathy. We sought to determine
      whether ACE genotype and other clinical factors were associated with loss of
      renal function after BMT. We determined the genotype of 106 adult allogeneic BMT
      recipients, who received a similar preparative regimen, survived 1 year, and had
      assessment of renal function up to 3 years after BMT. We found that the
      distribution of genotypes was similar to the general population; 29%, 51%, and
      20% for the DD, DI, and II genotypes, respectively. There was no statistical
      difference in patient survival between the three groups. Among all patients, the
      average creatinine clearance declined from 124 (95% CI 117, 131) to 89 (95% CI
      78, 100) ml/min over the 36 months after BMT. Decline in renal function over time
      was less for patients with the DD compared to the II genotype (P = 0.040). Renal
      function in patients with the DD genotype was also better than those with the DI
      genotype, but this was of borderline statistical significance (P = 0.055). Renal
      shielding reduced decline in renal function compared to no shielding (P = 0.026).
      We conclude that the ACE genotype does not seem to influence survival, but the DD
      genotype may be protective against renal injury after BMT. Furthermore, we
      confirm that renal shielding during TBI reduces the renal injury after BMT.

PMID- 11313677
TI  - High-efficiency volume reduction of cord blood using pentastarch.
AB  - Human umbilical cord blood (UCB) has been used successfully to treat a variety of
      genetic, hematological, and oncologic disorders. However, the low number of
      hematopoietic progenitor cells available in donated cord blood samples limits
      transplantation of cord blood to children and small adults. Reduction of the
      volume of umbilical cord blood is widely used in cord blood banking to reduce the
      storage requirements in large-scale UCB banks. Unfortunately, during the volume
      reduction process, up to 40% or more of the progenitor cells are lost using
      current reduction methods. This study describes a highly reproducible, double
      collection technique using Pentaspan to reduce UCB volume by red cell depletion.
      This results in the preservation of critical hematopoietic progenitor cells. The
      final volume of the leukocyte concentrates (LC) was 19.8 +/- 0.4 ml with 95% red
      cell depletion. The recovery of nucleated cells (NC), mononuclear cells (MNC),
      CD34(+) cells and colony-forming units (CFU) following double collection was 89%,
      94%, 96%, and 106%, respectively. This is significantly higher than the recovery
      from single collections, where recovery was 74%, 77%, 84%, and 91% for NC, MNC,
      CD34(+) and CFU, respectively. The double collection technique provides an
      efficient and highly reproducible method for the preparation of UCB for long-term
      storage and transplantation.

PMID- 11313679
TI  - A European reference protocol for quality assessment and clinical validation of
      autologous haematopoietic blood progenitor and stem cell grafts.
AB  - Recently, the regulatory authorities have begun to show interest in
      haematopoietic stem cell products. On a professional rather than a regulatory
      basis, the International Society for Hematotherapy and Graft Engineering (ISHAGE)
      has established the Foundation for the Accreditation of Haematopoietic Cell
      Therapy (FACHT), which has drawn up guidelines for standards and accreditation of
      such activity. In Europe, the regulatory environment with regard to
      haematopoietic stem cell grafts, processing and storage are currently less
      stringent. However, in 1998 the European Joint Accreditation Committee Euro
      ISHAGE/EBMT (JACIE) prepared a regulatory document 'Standards for Blood and
      Marrow Progenitor Cell Collection, Processing and Transplantation' which was
      approved by the EBMT General Assembly. The major objectives were to promote
      quality of medical and laboratory practice in haematopoietic progenitor cell
      transplantation. The standards extend and detail the pre-existing activity of
      EBMT centres including all phases of collection, processing and administration of
      these cells. This is the platform for the proposed reference protocol for CD34(+)
      cell enumeration and clinical validation of quality assessment to ensure that
      appropriate standards of work and product quality are established and will be
      maintained.

PMID- 11313680
TI  - Pharmacodynamics of tandem high-dose melphalan with peripheral blood stem cell
      transplantation in children with neuroblastoma and medulloblastoma.
AB  - Repeated high-dose (HD) chemotherapy with peripheral blood stem cell (PBSC)
      transplantation is a new modality aimed at increasing both the dose and its
      intensity in the treatment of chemosensitive tumours. The aim of this study was
      to evaluate the tolerance, pharmacokinetics (PK) and pharmacodynamics (PD) of HD
      single-agent melphalan administered over two consecutive courses (C1 and C2) in
      children. Twenty-one patients (10 girls) with a median age of 4.1 years (range 8
      months-14 years) were entered into this study. Five had metastatic neuroblastoma
      (NB) and 16 a cerebral primitive neuroectodermal tumour (PNET). Melphalan was
      given at a dose of 100 mg/m(2) every 21 days. PBSCs were infused at a median
      number of 2.98 x 10(6) CD34(+) cells/kg. Forty courses, ie 21 C1 and 19 C2, were
      administered. Both courses were well tolerated. The median duration of ANC <
      500/microl was 7 and 6 days after C1 and C2, respectively. Platelet recovery (not
      mandatory to continue the HD strategy) was achieved in 52% of courses. GI
      toxicity was mild to moderate. The melphalan AUC ranged from 177 to 475 microg
      small middle dotmin/ml (no difference between C1 and C2). Prolonged neutropenia
      was associated with a young age (P < 0.001) and a low amount of CFU-GM (P =
      0.002). A long time to platelet recovery was associated with a high AUC (P =
      0.004) and a young age (P = 0.02). Grade 1 or 2 GI toxicity was associated with a
      high AUC (P = 0.015). Partial remission was observed in 11/14 patients with
      measurable cerebral PNET. In conclusion, tandem HD melphalan is feasible and safe
      in children, and achieved a high response rate in cerebral PNET. The observed PK
      PD relationships may help us design PK-guided outpatient treatment.

PMID- 11313681
TI  - Pharmacokinetics of liposomal busulphan in man.
AB  - High doses of busulphan are used in conditioning regimens before stem cell
      transplantation. Great inter-patient variations in pharmacokinetics and a
      correlation between toxicity and high systemic exposure of busulphan have been
      shown in several studies. Some authors have suggested therapeutic drug monitoring
      and intravenous busulphan aiming to reduce the conditioning-related toxicity.
      Liposomal busulphan (LBu) might be an alternative to intravenous administration
      of high-dose busulphan in conditioning. In the present study, we investigated the
      pharmacokinetics of LBu in man. Seventeen consecutive patients were enrolled in
      the study. LBu as a single low dose (2 to 8 mg) was given to 12 patients (six
      adults and six children). Five patients received two high doses of LBu which
      replaced the first and the last doses of the conditioning regimen. The high dose
      of LBu was raised from 0.4 to 0.9 mg/kg. A significant linear correlation (r2 =
      0.928) was found between the dose of LBu and the area under the plasma
      concentration-time curve (AUC) (P < 0.001). AUC corrected for 1 mg/kg was 5491 +/
      912 ng.h/ml and 5955 +/- 627 ng.h/ml (low dose of LBu in children and adults,
      respectively) and 6167 +/- 1385 ng.h/ml and 6933 +/- 656 ng.h/ml (ie the first
      and the last high doses of LBu, respectively). No significant correlation was
      found between clearance and age or apparent volume of distribution and age (r2 =
      0.146 and r2 = 0.046, respectively). No toxicity related to the liposomal
      formulation of busulphan was observed. We conclude that LBu is suitable for
      conditioning before stem cell transplantation.

PMID- 11313682
TI  - Large populations of non-clonogenic early apoptotic CD34-positive cells are
      present in frozen-thawed peripheral blood stem cell transplants.
AB  - Apoptosis is the common cell death pathway which is initiated by a variety of
      different stimuli. The recognition of early apoptotic events would markedly
      improve reliability and convenience of apoptosis assays. In the present study the
      vital stain SytoR 16 in combination with the permeability marker 7-amino
      actinomycin D, (7-AAD) has been used to identify an early stage of apoptosis, not
      detected with trypan blue or 7-AAD alone or with conventional apoptosis tests and
      not consistently and only partly detected by the early apoptosis marker annexin
      V. The method was established using solid tumour cell lines treated with TNF.
      Subsequently we applied it to determine apoptotic populations in CD34(+)
      peripheral blood progenitor cells obtained from growth factor and/or chemotherapy
      mobilised patients and frozen/thawed according to standard stem cell
      transplantation protocols. In a cell line model as well as CD34(+) progenitor
      cells, different subpopulations with decreased SytoR 16 fluorescence (SytoR 16int
      or SytoR 16low, compared with the normal SytoR 16high) appeared which are not, or
      only partly, apoptotic using conventional techniques including morphology or 7
      AAD staining: eg percentages of SytoR 16(int)/7-AAD(-) and SytoR 16(low)/7-AAD(-)
      may amount to the majority of cells present in a particular CD34(+) sample.
      Second, upon further incubation these subpopulations become late
      apoptotic/secondary necrotic much faster than the unmodified SytoR 16high
      population, as determined with 7-AAD staining and morphology. Third, these cells
      have strongly or completely reduced clonogenic capacity for committed (CFU-GM)
      and early (LTC-IC, determined only for CD34(+) cells) progenitors. This technique
      needs the inclusion of a blocker of P-glycoprotein, which is highly active in
      CD34(+) progenitor cells. This prevents the interference of the detection of
      SytoR16(low) apoptotic cells by SytoR 16low cells resulting from P-glycoprotein
      activity. By comparison with other apoptosis markers we found that early
      apoptotic subpopulations were detected in the order SytoR 16 > annexin V > 7-AAD.
      In conclusion, the combination of SytoR 16 and 7-AAD detects apoptotic events
      earlier than conventional apoptosis techniques or annexin V. Compared to the
      presently available viability tests, it allows a much better estimation of the
      number of viable clonogenic CD34(+) cells after freeze/thawing.

PMID- 11313683
TI  - Recombinant human granulocyte colony-stimulating factor (rh-G-CSF) may accelerate
      hematopoietic recovery after HLA-identical sibling allogeneic peripheral blood
      stem cell transplantation.
AB  - We studied the effects of recombinant human granulocyte colony-stimulating factor
      (G-CSF) on hematopoietic recovery and clinical outcome in patients undergoing
      allogeneic peripheral blood stem cell (PBSC) transplantation. Fifty-six patients
      with hematological malignancies who underwent allogeneic PBSC transplantation
      between 1995 and 1998 were entered into this study. Twenty-eight patients who
      received daily G-CSF from day +1 after allogeneic PBSC transplantation until the
      absolute neutrophil count (ANC) reached >0.5 x 10(9)/l for 3 consecutive days
      were compared with 28 patients (control group) who did not receive G-CSF in a non
      randomized manner. The study group and the control group were comparable with
      respect to baseline patient and transplantation characteristics. Median times to
      ANC of >0.5 x 10(9)/l and 1 x 10(9)/l with or without G-CSF were 12 days (range 8
      21), 13 days (10-32) (P = 0.04) and 13 days (9-21), 15 days (11-44) (P = 0.02),
      respectively. Median times to reach a platelet count of >20 x 10(9)/l with and
      without G-CSF were 11 days (0-20) and 13 days (9-26), respectively (P = 0.03).
      The incidence of febrile episodes was significantly lower with G-CSF, 75% vs 100%
      (P = 0.008). Patients receiving G-CSF had less grade III-IV mucositis than those
      who did not receive G-CSF (P = 0.01). There was also no increase in the incidence
      and severity of acute GVHD in patients using G-CSF (P = 0.22). Although the
      number of relapsing patients was greater in the G-CSF group (seven vs three
      patients), this was not statistically significant (P = 0.24). Disease-free and
      overall survival rates did not differ between the two groups (P = 0.58 and 0.53,
      respectively). The administration of G-CSF after allogeneic PBSC transplantation
      provided faster neutrophil and platelet engraftment associated with less severe
      mucositis and less febrile episodes.

PMID- 11313684
TI  - Allogeneic bone marrow transplantation from partially mismatched related donors
      as therapy for primary induction failure acute myeloid leukemia.
AB  - The outcome of acute myeloid leukemia patients with primary refractoriness to
      conventional chemotherapy is extremely poor. Allogeneic bone marrow transplants
      with matched sibling or matched unrelated donors provide 10-20% disease-free
      survival in this setting. We analyzed our transplant experience using readily
      available partially mismatched related donor (PMRD) in patients with primary
      induction failure (PIF) AML. Between March 1994 and December 1998, 13 patients
      with PIF AML were transplanted from 0-3 HLA antigen mismatched donors. All 12
      evaluable patients engrafted at a median of day +16. Ten (77%) patients survived
      at least 100 days after transplant. Acute GVHD (grade II) was observed in one of
      12 patients. Chronic GVHD was seen in one of 10 patients surviving beyond day
      100. The major cause of failure was relapse of disease in six occurring 3-12
      months after PMRD BMT. Three patients are alive without disease 14, 36 and 45
      months post BMT with Karnofsky scores of 100%. The actuarial 3-year probabilities
      of relapse and disease-free survival were 0.54 and 0.19, respectively. We
      concluded that a PMRD graft is a viable option, comparable to the use of matched
      related or unrelated donors, in patients with PIF AML in whom time is of the
      essence.

PMID- 11313685
TI  - Alpha-interferon maintenance treatment is associated with improved survival after
      high-dose treatment and autologous stem cell transplantation in patients with
      multiple myeloma: a retrospective registry study from the European Group for
      Blood and Marrow Transplantation (EBMT).
AB  - The purpose of this study was to evaluate the effect of alpha-IFN maintenance
      treatment after autologous stem cell transplantation (ASCT) for multiple myeloma
      in a retrospective registry analysis. 473 patients with multiple myeloma who
      received IFN maintenance treatment ASCT were compared with 419 patients who did
      not receive IFN-treatment. Patients who were evaluable for response and in
      complete or partial remission at 6 months after ASCT were eligible, after
      excluding patients with graft failure. Cox proportional hazards assumptions were
      checked and handled by stratification. The prognostic variables unevenly
      distributed between the two groups were statistically corrected for in the Cox
      analysis. 391 patients reached complete remission (CR) after ASCT (203 in the IFN
      group and 188 in the no-IFN group) and 501 were in partial remission (PR, IFN
      270, no-IFN 231). Overall survival (OS) and progression-free survival (PFS) were
      significantly better in the IFN-group (OS, 78 vs 47 months, P = 0.007, and PFS,
      29 vs 20 months, P = 0.006, respectively). The difference in OS and PFS was most
      strongly pronounced in the PR patients. 209 patients have died (IFN, 84; no-IFN,
      125). Progressive myeloma was the cause of death in 94% of the IFN-treated
      patients and in 83% of the no-IFN group (P = NS). Thus, IFN maintenance treatment
      after ASCT was associated with better OS and PFS. Treatment seemed to be most
      beneficial in patients who did not achieve CR. The difference in median survival
      was as long as 2.5 years, and although part of this difference is attributable to
      differences in other prognostic factors, it might justify possible differences in
      quality-of-life due to adverse effects of interferon treatment.

PMID- 11313686
TI  - Detection of breast cancer cell contamination in leukapheresis product by real
      time quantitative polymerase chain reaction.
AB  - Identification of sensitive techniques for breast cancer cell detection might be
      relevant for high-dose chemotherapy programs with autologous stem cell
      transplantation. We investigated the feasibility of Maspin, Mammaglobin and c
      ErbB-2 amplification by real-time quantitative polymerase chain reaction (RQ-PCR)
      for the detection of breast cancer cells in leukaphereses. Expression of the
      three markers was determined in primary breast cancers and cell lines. Peripheral
      blood (PB), bone marrow (BM), and leukapheresis samples from patients with
      malignancies other than breast cancer were used as controls. Sensitivity was
      evaluated by dilution of primary tumors and cell lines with mononuclear blood
      cells. We found expression of the three markers in all primary tumors and most
      cell lines. No blood specimen from control patients had the Maspin transcript,
      while only one was positive for Mammaglobin. Weak c-ErbB-2 expression was
      detectable in most PB, all BM and all leukapheresis samples from controls. We
      observed a low sensitivity of Maspin RQ-PCR and a sensitivity of Mammaglobin RQ
      PCR up to one tumor cell in 10(6) mononuclear cells. One out of 18 leukaphereses
      from breast cancer patients screened for the presence of Mammaglobin mRNA was
      positive. We conclude that Mammaglobin RQ-PCR might be a useful tool for
      detection of leukapheresis contamination.

PMID- 11313687
TI  - Infectious complications after high-dose chemotherapy and autologous stem cell
      transplantation: comparison between patients with lymphoma or multiple myeloma
      and patients with solid tumors.
AB  - From November 1994 to May 1998, 117 patients (66 with solid tumor, 36 with
      lymphoma, 14 with multiple myeloma, one with acute leukemia) underwent 178 cycles
      of high-dose chemotherapy and autologous stem cell transplantation (ASCT) at our
      institution. We retrospectively analyzed the infectious complications that
      occurred after ASCT. Median duration of neutropenia (granulocyte count <0.5 x
      10(9)/l ) was 8 days, the overall incidence of fever requiring antimicrobial
      treatment was 63%. 35.4% of patients had fever of unknown orign (FUO), whereas
      primary bacteremia occurred in 21.3%, pneumonia in 3.4% and severe skin infection
      in 1.1% of patients. Invasive fungal infections occurred in three, and
      enterocolitis in one patient. Infection was fatal in three patients (2.6%), in
      each case due to septic shock. The most frequently isolated pathogens were Gram
      positive cocci. Median time to defervescence with antimicrobial therapy was 4
      days (6 days in patients with bacteremia or other severe infection, and 3 days in
      patients with FUO). First-line antimicrobial therapy was successful in 65% of
      patients with FUO and 30.6% of patients with documented infections. With respect
      to the incidence, type and clinical course of infection, no significant
      differences between patients with lymphoma or multiple myeloma and those with
      solid tumors were detected.

PMID- 11313688
TI  - Thrombotic microangiopathy: a new dose-limiting toxicity of high-dose sequential
      chemotherapy.
AB  - Ten patients with refractory (n = 8) or early relapsing (n = 2) aggressive non
      Hodgkin's lymphoma were enrolled in a pilot study evaluating a high-dose
      sequential chemotherapy regimen with peripheral blood stem cell (PBSC) support.
      Five treatment phases were scheduled: phase I (cyclophosphamide + etoposide
      followed by lenograstim (G-CSF), and a PBSC harvest); phase II (cisplatinum +
      cytarabine + etoposide followed by lenograstim); phases III and IV
      (cyclophosphamide + cytarabine + etoposide followed by autologous PBSC infusion
      and lenograstim); and phase V (carmustine + cytarabine + etoposide + melphalan
      followed by autologous PBSC infusion and lenograstim). Ten, nine, eight, six and
      four of the 10 patients received one, two, three, four and five of the five
      scheduled phases of treatment, respectively. Four patients were withdrawn from
      the study due to progressive disease and two due to thrombotic microangiopathy
      (TM). Moreover, in the four patients who completed all treatment phases, an
      additional case of TM was seen. In all three patients with TM, laboratory studies
      showed evidence of Coombs negative hemolytic anemia, thrombocytopenia, renal
      dysfunction and in addition cardiac failure in two patients. TM may be a new dose
      limiting toxicity of high-dose sequential chemotherapy followed by repeated PBSC
      transplantation.

PMID- 11313689
TI  - Dental health and viridans streptococcal bacteremia in allogeneic hematopoietic
      stem cell transplant recipients.
AB  - Viridans streptococci were the most common cause of bacteremia in 61 consecutive
      myeloablative allogeneic hematopoietic stem cell transplant (HSCT) recipients,
      occurring in 19 of 31 bacteremic patients (61%) during the period of post
      transplant neutropenia. Seven of the 19 had more than one viridans streptococcus
      in the same blood culture. Twenty isolates from 15 patients were Streptococcus
      mitis. Most viridans streptococci were resistant to norfloxacin, used routinely
      for prophylaxis. Comparison of the 19 patients with viridans streptococcal
      bacteremia with a contemporaneous group of 23 allogeneic HSCT recipients with
      fever and neutropenia but no identified focus of infection found that patients
      with viridans streptococcal bacteremia were more likely to have severe intraoral
      pathology while neutropenic (26% vs 0%) and slightly shorter interval between the
      last dental procedure and the onset of neutropenia (11 vs 14 days). Poor
      underlying dental health and the use of norfloxacin thus appear to predispose to
      viridans streptococcal bacteremia.

PMID- 11313691
TI  - Successful engraftment of a second transplant using non-myeloablative
      conditioning as treatment for graft failure following unrelated donor BMT.
AB  - A 32-year-old man with CML in second chronic phase developed primary graft
      failure following matched unrelated donor transplantation using cryopreserved
      marrow cells. He was successfully regrafted within 60 days from a second fully
      matched donor using a non-myeloablative conditioning regimen, with minimal
      toxicity. He remains in complete haematological, cytogenetic and molecular
      remission 2 years after second transplant. We believe that reduced intensity or
      'mini-transplants' may be preferable for patients requiring second allografts
      which are usually associated with a high transplant-related mortality.

PMID- 11313690
TI  - Early allogeneic blood stem cell transplantation after modified conditioning
      therapy during marrow aplasia: stable remission in high-risk acute myeloid
      leukemia.
AB  - Two patients with high-risk acute myeloid leukemia (AML) whose bone marrow
      aspirates showed more than 25% blasts between 2 and 4 weeks after the first
      induction chemotherapy immediately received modified conditioning therapy with
      intravenous busulfan at 50% of the usual dose and fludarabine, before hematologic
      recovery occurred. Unmanipulated G-CSF mobilized peripheral blood stem cells from
      an HLA-identical sibling donor were transfused and haematopoietic recovery was
      achieved in both recipients. Both of them are in continuing hematological
      remission with full donor chimerism 12 and 22 months after transplantation. Early
      treatment intensification with allogeneic cell therapy during marrow aplasia
      might cure high-risk AML patients who are unlikely to achieve remission with
      conventional chemotherapy protocols.

PMID- 11313692
TI  - Accidental busulfan overdose: enhanced drug clearance with hemodialysis in a
      child with Wiskott-Aldrich syndrome.
AB  - A 4.6 kg infant with Wiskott-Aldrich syndrome received an accidental overdose of
      busulfan during preparation for allogeneic stem cell transplantation.
      Pharmacokinetic analysis of plasma busulfan levels alerted staff to the dosing
      error. Hemodialysis was immediately performed and resulted in accelerated
      clearance of busulfan. There were no acute neurologic and hepatic side-effects of
      the busulfan overdose, and despite 2 months of cough accompanied by rales, the
      patient is now free of pulmonary symptoms. Stable partial donor chimerism
      occurred after transplantation. At present, the patient is thriving and infection
      free 12 months after transplantation, although his platelet count remains at the
      lower limit of normal.

PMID- 11313693
TI  - Aggressive neoplastic plasma cell growth with MLL gene rearrangement after high
      dose therapy with autologous stem cell support for multiple myeloma.
AB  - We report a case of a patient with IgA kappa multiple myeloma (MM) mobilized with
      etoposide and subsequently receiving high-dose melphalan (HDM) with stem cell
      support. She relapsed rapidly post transplantation. Southern blot and fluorescent
      in situ hybridization analysis showed MLL gene rearrangement in the myeloma
      cells, which was not detected in the sample at diagnosis or in the PBSC harvested
      with etoposide plus G-CSF. These observations suggest that clonal rearrangement
      of the MLL gene is caused by etoposide. Patients with MM undergoing HDM with stem
      cell rescue may be at an increased risk of not only secondary leukemia, but also
      secondary genetic abnormalities in myeloma cells, especially those receiving
      priming with etoposide for peripheral blood stem cell collection.

PMID- 11313694
TI  - Severe interstitial pneumonitis following high-dose cyclophosphamide, thiotepa
      and docetaxel: two case reports and a review of the literature.
AB  - The use of high-dose chemotherapy for metastatic breast cancer has been an area
      of recent interest and the role of such treatment in the management of metastatic
      breast cancer is still to be defined. Multiple studies have suggested that such
      treatment can be given with minimal morbidity and mortality. We describe two
      cases of life-threatening interstitial pneumonitis, following high-dose
      chemotherapy (HDT) with cyclophosphamide, thiotepa and docetaxel with stem cell
      rescue given for metastatic breast cancer. The available relevant literature is
      reviewed.

PMID- 11313696
TI  - Publications in cell death: the golden age.

PMID- 11313697
TI  - Cytokinesis, apoptosis and survivin: three for tango?

PMID- 11313698
TI  - DAP-kinase: from functional gene cloning to establishment of its role in
      apoptosis and cancer.
AB  - DAP-kinase is a pro-apoptotic Ca(2+) calmodulin-regulated serine/threonine kinase
      that participates in a wide array of apoptotic systems initiated by interferon
      gamma, TNF-alpha, activated Fas, and detachment from extracellular matrix. It was
      isolated by an unbiased functional approach to gene cloning aimed at hitting
      central mediators of the apoptotic process. This 160 Kd protein kinase is
      localized to actin microfilaments and carries interesting modules such as ankyrin
      repeats and the death domain. The death promoting effects of DAP-kinase depend on
      its intact catalytic activity, the correct intracellular localization, and on the
      presence of the death domain. A few mechanisms restrain the killing effects of
      the protein in healthy cells. The enzyme's active site is negatively controlled
      by an adjacent CaM regulatory domain whose effect is relieved by binding to
      Ca(2+)-activated calmodulin. A second mode of autoinhibition engages the serine
      rich C-terminal tail, spanning the last 17 amino acids of the protein. A link
      between DAP-kinase and cancer has been established. It was found that the mRNA
      and protein expression is frequently lost in various human cancer cell lines.
      Analysis of the methylation status of DAP-kinase's 5' UTR in DNA extracted from
      fresh tumor samples, showed high incidence of hypermethylation in several human
      carcinomas and B cell malignancies. The anti-tumorigenic effect of DAP-kinase was
      also studied experimentally in mouse model systems where the re-introduction of
      DAP-kinase into highly metastatic mouse lung carcinoma cells who had lost the
      protein, strongly reduced their metastatic capacity. Thus, it appears that loss
      of DAP-kinase confers a selective advantage to cancer cells and may play a
      causative role in tumor progression. A few novel kinases sharing high homology in
      their catalytic domains with DAP-kinase have been recently identified
      constituting altogether a novel family of death promoting serine/threonine
      kinases.

PMID- 11313699
TI  - Inhibition of mammary epithelial apoptosis and sustained phosphorylation of
      Akt/PKB in MMTV-IGF-II transgenic mice.
AB  - IGF-II is a growth factor implicated in human cancers and animal tumor models.
      While the mitogenic properties of IGF-II are well documented, its ability to
      suppress apoptosis in vivo has never been proven. We generated independent MMTV
      IGF-II transgenic mice to examine the control of epithelial apoptosis at the
      morphological, cellular and molecular levels during the physiological event of
      postlactation mammary involution. Transgenic IGF-II expression was achieved in
      mammary epithelium and increased IGF-II bioactivity was confirmed by
      phosphorylation of the insulin receptor substrate-1, a signaling molecule
      downstream of the type I IGF receptor. IGF-II overexpression induced a delay in
      mammary involution, as evident by increased mammary gland to body weight ratios
      and persistence of both functionally intact lobulo-alveoli and mammary epithelial
      cellularity. The delayed mammary involution resulted from a significant reduction
      in mammary epithelial apoptosis, and not from increased epithelial proliferation.
      Recombinant IGF-II pellets implanted into involuting mammary glands of wild-type
      mice provided further evidence that IGF-II protein inhibited local epithelial
      apoptosis. At the molecular level, phosphorylated Akt/PKB, but not Erk1 or Erk2,
      persisted in IGF-II overexpressors and temporally correlated with reduced
      epithelial apoptosis. Levels of the phosphatase PTEN were unaltered in the
      transgenic tissue suggesting that the maintenance of Akt/PKB phosphorylation
      resulted from sustained phosphorylation rather than altered dephosphorylation of
      PIP-3. Together, this data reveal that IGF-II inhibits apoptosis in vivo and this
      effect correlates with prolonged phosphorylation of Akt/PKB

PMID- 11313700
TI  - Quantitative analysis of fluorescent caspase substrate cleavage in intact cells
      and identification of novel inhibitors of apoptosis.
AB  - Caspase activation and proteolytic cleavage of specific target proteins
      represents an integral step in the pathway leading to the apoptotic death of
      cells. Analysis of caspase activity in intact cells, however, has been generally
      limited to the measurement of end-point biochemical and morphological markers of
      apoptosis. In an effort to develop a strategy with which to monitor caspase
      activity, early in the cell death cascade and in real-time, we have generated
      cell lines that overexpress recombinant GFP-based caspase substrates that display
      a quantifiable change in their spectral properties when cleaved by group II
      caspases. Specifically, tandem GFP substrates linked by a caspase-sensitive
      cleavage site show diminished fluorescence resonance energy transfer (FRET), as a
      consequence of cleavage, due to physical separation of the GFP moieties in
      apoptotic cells. We have evaluated the influence of different caspase-sensitive
      linkers on both FRET efficiency and cleavage by caspase-3. We also demonstrate
      that caspase activity as well as inhibition by pharmacological agents can be
      monitored, with minimal manipulation, in intact adherent cells seeded in a 96
      well cell culture dish. Finally, we have adapted this technology to a high
      throughput screening platform to identify novel small molecule and cell permeable
      inhibitors of apoptosis. Based on a biochemical analysis of the compounds
      identified it is clear that this assay can be used to detect drugs which inhibit
      caspases directly as well as those which target upstream components of the
      caspase cascade.

PMID- 11313701
TI  - Measurement of caspase activity in individual cells reveals differences in the
      kinetics of caspase activation between cells.
AB  - Most forms of apoptosis involve activation of caspases and it is likely that
      differences between cells in their ability to activate caspases contributes to
      the responsiveness of any given cell within a population to apoptotic stimuli. To
      study the molecular mechanisms that underlie such differences, it is necessary to
      measure caspase activity in individual cells. Here, we describe a method that
      allows the continuous monitoring of caspase activity in individual, living
      mammalian cells. This approach allows studies of the kinetics of caspase
      activation to be performed in individual cells within a population. We
      demonstrate that in a group of cells where some cells die and some cells survive
      in response to the same stimulus, the cells that die can be differentiated from
      those that survive based on the amount of caspase activity in each cell several
      hours before death occurs.

PMID- 11313702
TI  - Bcl-2 induces cyclin D1 promoter activity in human breast epithelial cells
      independent of cell anchorage.
AB  - Cyclin D1 expression is co-regulated by growth factor and cell adhesion
      signaling. Cell adhesion to the extracellular matrix activates focal adhesion
      kinase (FAK), which is essential for cyclin D1 expression. Upon the loss of cell
      adhesion, cyclin D1 expression is downregulated, followed by apoptosis in normal
      epithelial cells. Since bcl-2 prevents apoptosis induced by the loss of cell
      adhesion, we hypothesized that bcl-2 induces survival signaling complementary to
      cell adhesion-mediated gene regulation. In the present study, we investigated the
      role of bcl-2 on FAK activity and cyclin D1 expression. We found that bcl-2
      overexpression induces cyclin D1 expression in human breast epithelial cell line
      MCF10A independent of cell anchorage. Increased cyclin D1 expression in stable
      bcl-2 transfectants is not related to bcl-2-increased G1 duration, but results
      from cyclin D1 promoter activation. Transient transfection studies confirmed
      anchorage-independent bcl-2 induction of cyclin D1 promoter activity in human
      breast epithelial cell lines (MCF10A, BT549, and MCF-7). We provide evidence that
      bcl-2 induction of cyclin D1 expression involves constitutive activation of focal
      adhesion kinase, regardless of cell adhesion. The present study suggests a
      potential oncogenic activity for bcl-2 through cyclin D1 induction, and provides
      an insight into the distinct proliferation-independent pathway leading to
      increased cyclin D1 expression in breast cancer.

PMID- 11313704
TI  - Resting membrane potential as a marker of apoptosis: studies on Xenopus oocytes
      microinjected with cytochrome c.
AB  - Observation of the electrical potential difference across the cell membrane is
      described as a new method for monitoring apoptosis of a single cell. The resting
      membrane potential (DeltaPsi) of Xenopus oocytes has been recorded in real time
      following microinjection of cytochrome c. Soon after microinjection, DeltaPsi
      becomes less negative and attains a new constant value with a half time, t(m), of
      about 35 (+ /- 5) min at all cytochrome c concentrations greater than 1 microM.
      The cytosol extract of cytochrome c-injected oocytes shows DEVD proteolytic
      activity characteristic of aspartate specific proteases, implicating an apoptotic
      death pathway. In response to the delivery of cytochrome c into the cytosol,
      caspases are activated within 7 min while the changes in DeltaPsi begin to occur
      after about 30 min. The method described here will be potentially useful to
      assess the effectiveness of cell death regulators and modulators of synthetic and
      biological origin, and the results presented shed light on the currently debated
      issue of the importance of the redox state of cytochrome c in the initiation of
      apoptosis.

PMID- 11313703
TI  - Ectopic expression of cyclin D1 impairs the proliferation and enhances the
      apoptosis of a murine lymphoid cell line.
AB  - Cyclin D1, a key regulator of the cell cycle, acts as an oncogene when over
      expressed in several types of cancer. In some B-chronic lymphoproliferative
      disorders, the over-expression of cyclin D1 protein is thought to confer a
      proliferative phenotype. We have generated BaF3 pro-B cell derivatives in which
      cyclin D1 can be induced rapidly and reversibly in a dose-dependent manner by the
      hormone muristerone A. When non-expressing clones displayed the same
      proliferative capacity as the parental cell line, in the sub-clones, a moderate
      induction of cyclin D1 lengthened the proliferation rate. The over-expression of
      cyclin D1 had the same effects on cell proliferation but also led ultimately to
      cell death by apoptosis. The induction of cyclin D1 in growth factor-deprived
      cells as well as in anticancer drug-treated cells also reinforced the magnitude
      of apoptosis. Thus, the expression of cyclin D1 in lymphoid cells does not confer
      a proliferative advantage but rather alters the response of cells towards
      apoptotic stimuli in a p53-independent manner.

PMID- 11313705
TI  - A functionally active RARalpha nuclear receptor is expressed in retinoic acid non
      responsive early myeloblastic cell lines.
AB  - Although all-trans retinoic acid (ATRA) can restore the differentiation capacity
      of leukemic promyelocytes, early leukemic myeloblasts are conversely not
      responsive to ATRA induced granulocytic differentiation. To assess whether this
      resistance to ATRA is related to an impaired function of the Retinoic Acid
      Receptor alpha (RARalpha), we performed an analysis of RARalpha expression and
      transactivation activity, in several myeloid leukemic cell lines, representative
      of different types of spontaneous acute myeloid leukemias. Our results indicate
      that a functionally active RARalpha nuclear receptor is expressed in all the
      analyzed cell lines, regardless of their differentiation capacity following
      exposure to ATRA. The observation that ATRA treatment is able to induce the
      expression of retinoic acid target genes, in late- but not in early-myeloblastic
      leukemic cells, raises the possibility that the differentiation block of these
      cells is achieved through a chromatin mediated mechanism. Acetylation is
      apparently not involved in this process, since the histone deacetylase inhibitor
      trichostatin A, is not able to restore the differentiation capacity of early
      leukemic myeloblasts. Further investigation is needed to clarify whether myeloid
      transcription factors, distinct to RARalpha, play a role in the resistance of
      these cells to ATRA treatment.

PMID- 11313709
TI  - Of umbrellas, jazz and slow-steppin'.

PMID- 11313707
TI  - Niemann-Pick Disease versus acid sphingomyelinase deficiency.

PMID- 11313711
TI  - Apoptosis in viral pathogenesis.

PMID- 11313706
TI  - Ceramide generation occurring during 7beta-hydroxycholesterol- and 7
      ketocholesterol-induced apoptosis is caspase independent and is not required to
      trigger cell death.
AB  - Biological activities of oxysterols seem tightly regulated. Therefore, the
      ability to induce cell death of structurally related oxysterols, such as those
      oxidized at C7(7alpha-, 7beta-hydroxycholesterol, and 7-ketocholesterol), was
      investigated on U937 cells at different times of treatment in a concentration
      range of 5-80 microg/ml. Whereas all oxysterols accumulate inside the cells,
      strong inhibition of cell growth and increased permeability to propidium iodide
      were observed only with 7beta-hydroxycholesterol and 7-ketocholesterol, which
      trigger an apoptotic process characterized by the occurrence of cells with
      fragmented and/or condensed nuclei, and by various cellular dysfunctions: loss of
      mitochondrial transmembrane potential, cytosolic release of cytochrome c,
      activation of caspase-9 and -3 with subsequent enhanced activity of caspase-3,
      degradation of poly(ADP-ribose) polymerase, and increased accumulation of
      cellular C16 : 0 and C24 : 1 ceramide species. This ceramide generation is not
      attributed to caspase activation since inhibition of 7beta-hydroxycholesterol-
      and 7-ketocholesterol-induced apoptosis by Z-VAD-fmk (100 microM), a broad
      spectrum caspase inhibitor, did not reduce C16 : 0 and C24 : 1 ceramide species
      accumulation. Conversely, when U937 cells were treated with 7beta
      hydroxycholesterol and 7-ketocholesterol in the presence of fumonisin B1 (100
      microM), a specific inhibitor of ceramide synthase, C16 : 0 and C24 : 1 ceramide
      species production was completely abrogated whereas apoptosis was not prevented.
      Noteworthy, 7alpha-hydroxycholesterol induced only a slight inhibition of cell
      growth. Collectively, these results are consistent with the notion that the alpha
      or beta hydroxyl radical position of oxysterols oxidized at C7 plays a key role
      in the induction of the apoptotic process. In addition, our findings demonstrate
      that 7beta-hydroxycholesterol- and 7-ketocholesterol-induced apoptosis involve
      the mitochondrial signal transduction pathway and they suggest that C16 : 0 and
      C24 : 1 ceramide species generated through ceramide synthase play a minor role in
      the commitment of 7beta-hydroxycholesterol- and 7-ketocholesterol-induced cell
      death.

PMID- 11313712
TI  - Lois K Miller.

PMID- 11313713
TI  - Host defense, viruses and apoptosis.
AB  - To thwart viral infection, the host has developed a formidable and integrated
      defense network that comprises our innate and adaptive immune response. In recent
      years, it has become clear that in an attempt to prevent viral replication, viral
      dissemination or persistent viral infection of the cell, many of these protective
      measures actually involve the induction of programmed cell death, or apoptosis.
      An initial response to viral infection primarily involves the innate arm of
      immunity and the killing of infected cells with cytotoxic lymphocytes such as
      natural killer (NK) cells through mechanisms that include the employment of
      perforin and granzymes. Once the virus has invaded the cell, however, a second
      host defense-mediated response is also triggered which involves the induction of
      a family of cytokines known as the interferons (IFNs). The IFNs, which are
      essential for initiating and coordinating a successful antiviral response,
      function by stimulating the adaptive arm of immunity involving cytotoxic T cells
      (CTLs), and by inducing a number of intracellular genes that directly prevent
      virus replication/cytolysis or that facilitate apoptosis. The IFN-induced gene
      family is now known to comprise the death ligand TRAIL, the dsRNA-dependent
      protein kinase (PKR), interferon regulatory factors (IRFs) and the promyelocytic
      leukemia gene (PML), all of which have been reported to be mediators of cell
      death. That DNA array analyses indicate that numerous cellular genes, many as yet
      uncharacterized, may similarly be induced by IFN, further emphasizes the likely
      importance that these cytokines have in the modulation of apoptosis. This
      likelihood is additionally underlined by the elaborate strategies developed by
      viruses to inhibit IFN-antiviral function and the mechanisms of cell death.

PMID- 11313714
TI  - Biochemical mechanisms of HIV induced T cell apoptosis.

PMID- 11313715
TI  - Baculoviruses and apoptosis: the good, the bad, and the ugly.
AB  - Since 1991, when a baculovirus was first shown to inhibit apoptosis of its host
      insect cells, considerable contributions to our knowledge of apoptosis have
      arisen from the study of these viruses and the anti-apoptotic genes they encode.
      Baculovirus anti-apoptotic genes include p35, which encodes the most broadly
      acting caspase inhibitor protein known, and iap (inhibitor of apoptosis) genes,
      which were the first members of an evolutionarily conserved gene family involved
      in regulation of apoptosis and cytokinesis in organisms ranging from yeast to
      humans. Baculoviruses also provide an ideal system to study the effects of an
      apoptotic response on viral pathogenesis in an animal host. In this review, I
      discuss a number of interesting recent developments in the areas of apoptotic
      regulation by baculoviruses and the effects of apoptosis on baculovirus
      replication and pathogenesis.

PMID- 11313716
TI  - Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis
      in J774 macrophages.
AB  - We investigated the role of constitutive transcription factor nuclear factor
      kappaB (NF-kappaB) in nitric oxide (NO)-mediated apoptosis in J774 macrophages.
      Our results show that NF-kappaB is present in untreated J774 cells in a form
      constitutively active. Incubation of cells with sodium nitroprusside (SNP) and S
      nitroso-glutathione (GSNO), two NO-generating compounds, caused: (a) inhibition
      of constitutive NF-kappaB/DNA binding activity; (b) decrease of cell viability;
      (c) DNA fragmentation; (d) ApopTag positivity. Pyrrolidine dithiocarbamate (PDTC)
      and N-alpha-para-tosyl-L-lysine chloromethyl ketone (TLCK), two inhibitors of NF
      kappaB activation, showed the same effects of both NO-generating compounds.
      Furthermore, SNP and GSNO as well as PDTC and TLCK significantly increased the
      cytoplasmic level of IkappaBalpha. All together these results demonstrate that
      constitutive NF-kappaB protects J774 macrophages from NO-induced apoptosis.
      Moreover, these findings show, for the first time, that NO-generating compounds
      may induce apoptosis in J774 macrophages by down-regulating constitutive NF
      kappaB/DNA binding activity and suggest a novel mechanism by which NO induces
      apoptosis.

PMID- 11313717
TI  - Zinc-mediated regulation of caspases activity: dose-dependent inhibition or
      activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos).
AB  - Divalent cations, including Zinc and Manganese ions, are important modulators of
      cell activation. We investigated the ability of these two divalent cations to
      modulate apoptosis in human Burkitt lymphoma B cells line (Ramos). We found that
      Zinc (from 10 to 50 microM) inhibited Manganese-induced caspase-3 activation and
      apoptosis of Ramos cells. Higher concentration of Zinc (50 to 100 microM) did not
      prevent Manganese-mediated apoptosis but rather increased cell death among Ramos
      cells. This Zinc-mediated cell death was associated with apoptotic features such
      as cell shrinkage, the presence of phosphatidylserine residues on the outer
      leaflet of the cells, chromatin condensation, DNA fragmentation and decrease of
      mitochondrial transmembrane potential. Zinc-mediated apoptosis was associated
      with caspase-9 and caspase-3 activation as revealed by the appearance of active
      p35 fragment of caspase-9 and p19 and p17 of caspase-3 as well as in vivo
      cleavage of PARP and of a cell-permeable fluorogenic caspase-3 substrate
      (Phiphilux-G(1)D(2)). Both Zinc-mediated apoptosis and caspase-3 activation were
      prevented by the cell-permeable, broad-spectrum inhibitor of caspases (zVAD-fmk)
      or overexpression of bcl-2. In addition, we show that Zinc-induced loss of
      transmembrane mitochondrial potential is a caspase-independent event, since it is
      not modified by the presence of zVAD-fmk, which is inhibited by overexpression of
      bcl-2. These results indicate that depending on its concentration, Zinc can exert
      opposite effects on caspase-3 activation and apoptosis in human B lymphoma cells:
      concentrations below 50 microM inhibit caspase-3 activation and apoptosis whereas
      higher concentrations of Zinc activate a death pathway associated with apoptotic
      like features and caspase-3 activation.

PMID- 11313719
TI  - Activation of protein kinase C inhibits TRAIL-induced caspases activation,
      mitochondrial events and apoptosis in a human leukemic T cell line.
AB  - TRAIL causes apoptosis in numerous types of tumor cells. However, the mechanisms
      regulating TRAIL-induced apoptosis remain to be elucidated. We have investigated
      the role of PKC in regulating TRAIL-induced mitochondrial events and apoptosis in
      the Jurkat T cell line. We found a caspase-dependent decline in mitochondrial
      membrane potential and translocation of cytochrome c from mitochondria into the
      cytosol in response to TRAIL. Both these events were prevented by PKC activation.
      Moreover, PKC activation considerably reduced the activation of caspases, PARP
      cleavage and apoptosis when induced upon TRAIL treatment. MAPK activation was
      involved in the mechanism of PKC-mediated inhibition of TRAIL-induced cytochrome
      c release from mitochondria. Furthermore, inhibition of the MAPK pathway
      partially reversed the PKC-mediated inhibition of TRAIL-induced apoptosis.
      Besides, PKC activation may also inhibit the TRAIL-induced apoptosis through a
      MAPK-independent mechanism. Altogether, these results indicate a negative role of
      PKC in the regulation of apoptotic signals generated upon TRAIL receptor
      activation.

PMID- 11313718
TI  - Sphingosine generation, cytochrome c release, and activation of caspase-7 in
      doxorubicin-induced apoptosis of MCF7 breast adenocarcinoma cells.
AB  - Treatment of human breast carcinoma MCF7 cells with doxorubicin, one of the most
      active antineoplastic agents used in clinical oncology, induces apoptosis and
      leads to increases in sphingosine levels. The transient generation of this
      sphingolipid mediator preceded cytochrome c release from the mitochondria and
      activation of the executioner caspase-7 in MCF7 cells which do not express
      caspase-3. Bcl-x(L) overexpression did not affect sphingosine generation whereas
      it reduced apoptosis triggered by doxorubicin and completely blocked apoptosis
      triggered by sphingosine. Exogenous sphingosine-induced apoptosis was also
      accompanied by cytochrome c release and activation of caspase-7 in a Bcl-x(L)
      sensitive manner. Furthermore, neither doxorubicin nor sphingosine treatment
      affected expression of Fas ligand or induced activation of the apical caspase-8,
      indicating a Fas/Fas ligand-independent mechanism. Our results suggest that a
      further metabolite of ceramide, sphingosine, may also be involved in mitochondria
      mediated apoptotic signaling induced by doxorubicin in human breast cancer cells.

PMID- 11313720
TI  - Early stages of p53-induced apoptosis are reversible.
AB  - Apoptosis is a type of physiological cell death that occurs during development,
      normal tissue homeostasis, or as a result of different cellular insults. The
      phenotype of an apoptotic cell is relatively consistent in most cases of
      apoptosis and involves at least changes in the cell membrane, proteolysis of
      cytoplasmic and nuclear proteins, and eventual destruction of nuclear DNA. Our
      laboratory is interested in the reversibility of apoptosis. We have initial
      evidence that DNA repair is activated early in p53-induced apoptosis and may be
      involved in its reversibility. The present work further strengthens our
      proposition that p53-induced apoptosis is reversible. We show that p53 activation
      induces phosphatidylserine (PS) externalization early in apoptosis, and that
      these early apoptotic cells with externalized PS can be rescued and proliferate
      if the apoptotic stimulus is removed. In addition, we show that unscheduled DNA
      synthesis occurs in early apoptotic cells, and that if DNA repair is inhibited by
      aphidicolin, apoptosis is accelerated. These results confirm that early p53
      induced apoptotic cells can be rescued from the apoptotic program, and that DNA
      repair can modulate that cell death process.

PMID- 11313723
TI  - Overexpression of Bcl-2 enhances sensitivity of L929 cells to a lipophilic
      cationic photosensitiser.

PMID- 11313721
TI  - Paracrine regulation of apoptosis by steroid hormones in the male and female
      reproductive system.
AB  - In males, androgens are essential in maintaining the integrity of the prostate.
      Androgen-ablation induces apoptosis of the prostatic epithelium. In females,
      ovariectomy induces apoptosis in uterine epithelium while progesterone inhibits
      this process. The objective of this study was to determine whether androgen and
      progesterone inhibit apoptosis, respectively, in mouse prostatic and uterine
      epithelia via steroid receptors in the epithelium or in the stroma. To address
      this question, prostatic tissue recombinants were prepared with rat urogenital
      sinus mesenchyme plus bladder epithelium from wild-type or testicular
      feminization mutant (Tfm) mice. Thus, prostatic tissue was generated having
      androgen receptor (AR) in both epithelium and stroma or in the stroma only.
      Castration of hosts induced apoptosis in the AR-negative Tfm prostatic epithelium
      with an epithelial apoptotic index virtually identical to prostatic tissue
      recombinants containing wild-type epithelium. Moreover, this castration-induced
      prostatic epithelial apoptosis was blocked by testosterone and
      dihydrotestosterone in both wild-type and Tfm prostatic tissue recombinants.
      Likewise, uterine tissue recombinants were prepared in which epithelium and/or
      stroma was devoid of progesterone receptor (PR) by using uterine epithelium and
      stroma of wild-type and PR knockout mice. Progesterone inhibited uterine
      epithelial apoptosis only in tissue recombinants prepared with PR-positive
      stroma. The PR status of the epithelium did not affect epithelial apoptotic
      index. Therefore, the apoptosis in prostatic and uterine epithelia is regulated
      by androgen and progesterone via stromal AR and PR, respectively. In both cases,
      epithelial AR or PR is not required for hormonal regulation of epithelial
      apoptosis in prostatic and uterine epithelium.

PMID- 11313722
TI  - Cloning, chromosomal assignment and tissue distribution of human GILZ, a
      glucocorticoid hormone-induced gene.

PMID- 11313724
TI  - Radiographic digital image enhancement. Part II: transform domain techniques.
AB  - Digital image enhancement techniques can have a significant impact on the
      diagnostic quality of a radiographic image. Selection of an image enhancement
      technique is a function of image content and its attributes of interest. The
      diagnostic value of a radiographic image is commonly reduced by its intrinsic
      limitations as well as interference from unwanted signals. In this second article
      on radiographic image enhancement the Fourier transform, the most commonly used
      transformation method, is used to examine examples of methods for image
      enhancement, with particular emphasis on the removal or reduction of noise.

PMID- 11313725
TI  - Systematic review in diagnostic radiology.
AB  - Systematic review (SR) already makes a major contribution to evidence-based
      healthcare by making the review process transparent and by reducing bias. SR has
      been successfully applied to observational studies. Radiologists have already
      begun to make an impact in dentistry by using SR as a decision-making tool.
      Central to SR is establishment of a research question, selection criteria, a
      search plan, a literature search, an appraisal of the identified literature by
      the selection criteria; an analysis and a formulation of recommendations. With
      regard to the literature search, electronic databases (Medline, Embase, Science
      Citation Index, Lilacs), controlled subject headings, exploding and free-text
      searching, handsearching and the gray literature are discussed.

PMID- 11313726
TI  - Group learning factors in a problem-based course in oral radiology.
AB  - OBJECTIVES: To assess the development of group dynamics in students who
      participated in a problem-based learning (PBL) course in oral radiology and to
      evaluate the influence of the facilitators' experience. METHODS: At the beginning
      and end of the course, students in three consecutive years (1997, 1998 and 1999)
      responded to a group learning factor questionnaire designed to measure group
      dynamics (engagement, interpersonal relationships, lack of commitment and
      disruptive behaviour, interpersonal learning and self-presentation). The answers
      were analysed with paired t-test and the effects of the facilitator's seniority,
      expertise in oral radiology, experience of PBL and single or rotating
      facilitators assessed. RESULTS: Most groups in the three years reported above
      average group dynamic scores. There were significant changes in group dynamics.
      In the 1997 class, interpersonal relationships improved (P=0.014). In the 1998
      class, interpersonal learning (P=0.021) and engagement (P=0.009) increased
      significantly, while disruptive behaviour decreased (P=0.031). In the 1999 class,
      lack of commitment and disruptive behaviour decreased (P=0.014). Groups led by a
      junior faculty member with no previous experience of PBL show less commitment and
      more disruptive behaviour. CONCLUSIONS: More commitment and less disruptive
      behaviour and improved engagement, interpersonal relationships and self
      presentation were found in a PBL course in oral radiology. Facilitators should
      have prior exposure to PBL to avoid disruptive behaviour among the students.

PMID- 11313727
TI  - Resorption of the lateral pole of the mandibular condyle in temporomandibular
      disc displacement.
AB  - OBJECTIVES: To assess the possible relationship between resorption of the
      superolateral pole of the mandible condyle (RSLC) and TMJ disk displacement.
      METHODS: Two hundred and seventeen TMJs in 138 patients were studied.
      Displacement of the disc, degree of displacement and disc configuration were
      assessed using MRI. RSLC was assessed from a transorbital radiograph. RESULTS:
      Seventy-two joints (37%) were considered to have RSLC. A significantly higher
      prevalence of RSLC was found in joints with disc displacement (goodness test of
      fit for chi-square, P<0.05). A significantly higher prevalence of RSLC was found
      in joints with advanced disc displacement and advanced disk deformation (Mann
      Whitney U-test, P<0.01). CONCLUSIONS: RSLC appears more likely to occur in joints
      with advanced disc displacement.

PMID- 11313728
TI  - Detection of simulated periodontal bone gain by digital subtraction radiography
      with tuned-aperture computed tomography. The effect of angular disparity.
AB  - OBJECTIVES: To investigate the influence of angular disparity on observer
      detection of simulated bone gain in digital subtraction radiography using tuned
      aperture computed tomography (TACT). MATERIALS AND METHODS: Simulated periodontal
      defects were created in interproximal and buccal or lingual (tooth-obscured)
      areas of the premolar and molar regions of a dry human skull. Radiographs were
      obtained before and after known weights of amorphous bone were added to the
      defects to simulate bone gain. The skull was positioned in a multidirectional
      tomographic unit to achieve reproducibility. A series of nine basis images were
      acquired with a CMOS intra-oral receptor and repeated using angular disparities
      of 10 degrees, 20 degrees, and 30 degrees. Stacks of TACT slices generated from
      the basis images were paired for image-registration, histogram-equalization and
      subtraction using TACT Workbench. Eight calibrated observers randomly assessed
      the presence or absence of bone gain using a 5-point confidence scale. ROC curves
      were generated and A(z) values were analysed using ANOVA. RESULTS: There were
      significant differences in the performance of the observers (P=0.034), defect
      location (P=0.005), amount of bone gain (P<0.001), angular disparity (P=0.003)
      and angular disparity x defect location interaction (P=0.019). Mean A(z) values
      in detecting bone gain were 0.90, 0.85, 0.79 for angular disparities of 10
      degrees, 20 degrees, and 30 degrees respectively. CONCLUSIONS: Smaller angular
      disparity provided better detection of bone gain with TACT-subtraction using nine
      basis-projections. This effect of angular disparity was especially evident with
      tooth-obscured defects.

PMID- 11313729
TI  - Evaluation of a new digital panoramic system: a comparison with film.
AB  - OBJECTIVES: To evaluate the diagnostic efficacy of the Orthophos DS digital
      panoramic system (Sirona, Bensheim, Germany) for the detection of dento-alveolar
      disease in comparison with film. METHODS: Five patients selected for admission to
      the School of Dentistry had a panoramic radiograph obtained with the Orthophos
      Plus (Sirona, Bensheim, Germany) system, a digital panoramic image obtained with
      the Orthophos DS (Sirona, Bensheim, Germany) system and a full mouth series. The
      ground truth was determined from the full mouth series by a panel of board
      certified oral and maxillofacial radiologists using the Delphi method. Four
      observers scored both the film and digital panoramic images for the presence of
      caries and marginal periodontitis. Results were statistically analysed using ROC
      analysis and ANOVA. RESULTS: There was no significant difference (P=0.704)
      between the two modalities for the detection of caries but there was a
      significant difference (P=0.015) for the detection of periodontal disease where
      conventional panoramic film performed better than the digital image. CONCLUSIONS:
      Though the conventional film was better than the digital image for the detection
      of periodontal disease, further studies are needed to determine the clinical
      significance of this result in relation to the potential advantages of digital
      technology.

PMID- 11313730
TI  - Diagnostic yield of conventional and digital cephalometric images: a human
      cadaver study.
AB  - OBJECTIVES: To compare the clinical efficacy of digital and conventional
      cephalometric imaging. METHODS: Conventional and photostimulable phosphor
      cephalometric radiographs were obtained from three human cadavers at nine
      different exposure settings. Subjective image quality was assessed by six
      observers who evaluated six cephalometric landmarks. Organ doses were measured
      with TLDs and effective doses calculated. RESULTS: Compared with conventional
      cephalometric images, digital images had a consistently better subjective image
      quality for all exposure settings which was significant (P<0.05) for all but two.
      Organ doses were comparable. Higher kV and lower mAs settings yielded the lowest
      effective dose, which was highly dependent on the position of the thyroid gland
      in the beam. CONCLUSION: Relatively small variations in exposure settings do not
      influence subjective diagnostic image quality of digital cephalometric
      radiographs. Higher kV and lower mAs settings have the lowest effective dose and
      should therefore be preferred.

PMID- 11313731
TI  - Root fracture detection: a comparison of direct digital radiography with
      conventional radiography.
AB  - OBJECTIVES: To compare the diagnostic potential of direct digital radiography
      with conventional film for detecting experimental root fractures. METHODS: Two
      hundred and one extracted single-rooted human teeth were endodontically
      instrumented and divided into two groups, a control group of 100 teeth and a
      fractured group of 101 teeth in which root fractures were produced
      experimentally. Each tooth was imaged using the paralleling technique with a CCD
      based digital system and D-speed film. The images were interpreted by an
      experienced radiologist without prior knowledge of the distribution of the root
      fractures. The degree of agreement in detecting root fractures with each imaging
      system compared with the actual condition was expressed as the kappa value. The
      difference between the radiographic systems was then assessed by chi(2)-test at
      the 95% significance level. RESULTS: There was substantial agreement between the
      digital system and the actual condition (kappa=0.71; 95% Confidence Interval:
      0.62 to 0.80) and close agreement between the film and the actual condition
      (kappa=0.63; 95% Confidence Interval: 0.53 to 0.74). However, this difference was
      not significantly different (P=0.2). CONCLUSIONS: The performance of CCD-based
      digital radiography in detecting root fractures is similar to film-based
      radiography.

PMID- 11313732
TI  - Performance of a new F-speed film for caries detection.
AB  - OBJECTIVE: To compare films from three speed groups for the detection of
      approximal caries. STUDY DESIGN: Insight, Ektaspeed Plus and Ultra-speed (Eastman
      Kodak, Rochester, NY, USA) radiographs of the proximal surfaces of 40 extracted
      posterior teeth were evaluated by six observers. The presence or absence of
      caries was scored using a 5-point confidence scale. The actual status of each
      surface was determined from histology of ground sections. Observer responses were
      evaluated using ROC analysis and areas under the ROC curves (A(Z)) assessed using
      ANOVA. RESULTS: Ultra-speed film had a mean A(Z) of 0.88, Ektaspeed Plus 0.85,
      and Insight 0.84. These differences were not statistically significant (P=0.5).
      Differences between observers were also not statistically significant (P=0.42).
      CONCLUSIONS: The performance of the new F-speed film was not statistically
      different from E or D speed for caries detection. This film shows promise as a
      means of reducing patient dose while maintaining diagnostic quality.

PMID- 11313733
TI  - Osteoradionecrosis of the mandible. Comparison of the effects of external beam
      irradiation and brachytherapy.
AB  - OBJECTIVE: To compare the difference in location and severity of
      osteoradionecrosis (ORN) of the mandible following either external beam
      irradiation alone or combined with brachytherapy in the management of orofacial
      cancer. METHODS: CT was used to evaluate ORN in relation to the radiation source
      and field and the site of malignancy in 31 patients with orofacial carcinomas.
      Twenty-three patients received combined radiotherapy and brachytherapy and eight
      patients only external radiotherapy. The radiation dose distribution to the
      mandible was calculated retrospectively. RESULTS: In the combined radiotherapy
      group all patients had ORN of the lingual cortex, mostly adjacent to the position
      of previous iridium implants. Lingual defects were also found in the
      contralateral mandible in 35% of patients. Defects in the buccal cortex were seen
      in 30%. In the external radiotherapy group, ORN was found in both buccal and
      lingual cortices and 50% also in the contralateral mandible. When brachytherapy
      with iridium implants was used the dose to the buccal cortex was about one-third
      of that to the lingual cortex. There was no dose gradient between the cortices
      using external beam irradiation alone. CONCLUSIONS: Evidence of ORN was found in
      both groups of irradiation regimens. Thus, the entire irradiated mandible should
      be considered as a compromised tissue at risk of ORN.

PMID- 11313734
TI  - Variability in measurement of radiomorphometric indices by general dental
      practitioners.
AB  - OBJECTIVES: To assess the variability of general dental practitioners (GDPs) in
      measurement of radiomorphometric indices on panoramic radiographs following basic
      instruction and to examine whether the variability could be reduced by more
      individualised instruction. METHODS: Nine GDPs measured Gonion Index (GI),
      Antegonion Index (AI), Mental Index (MI) and Mandibular Cortical Index (MCI) on
      copies of 10 panoramic radiographs following a lecture on osteoporosis and the
      use of radiomorphometric indices. Their measurements were related to expert
      derived measurements of the same copy radiographs. Mean differences and limits of
      agreement (2x standard deviation of differences) were calculated for quantitative
      indices (GI, AI, MI) and agreement of GDPs with expert-derived MCI assessments
      was determined using weighted kappa. Following individualised feedback to GDPs,
      all measurements were repeated after 2 weeks and the statistical analysis
      repeated. RESULTS: There was extensive variation amongst GDPs in measurement of
      GI, AI and MI and in assessment of MCI. There was a general tendency of GDPs to
      record thicker mandibular cortices than did the experts. Limits of agreement were
      wide relative to the mean values of each quantitative index at both readings.
      Agreement of the GDPs with experts in assessment of MCI was moderate at both
      readings, but with a wide range in assessment. CONCLUSIONS: Variability in
      measuring radiomorphometric indices amongst the GDPs was high and was not
      predictably improved by individualised instruction. This study casts considerable
      doubt on the potential value of radiomorphometric indices given their lack of
      precision.

PMID- 11313735
TI  - An optimized fast protocol for magnetic resonance imaging of the
      temporomandibular joint.
AB  - OBJECTIVES: To provide a fast protocol for MR imaging of the TMJ with high
      contrast resolution of both soft tissue and joint fluid. METHODS: A fast turbo
      spin echo (TSE) pulse sequence was developed. The new technique was compared with
      T1W conventional spin echo (CSE) and T2W TSE sequences in imaging 57 TMJs in 50
      patients. Disc location and contour and bone delineation were assessed on three
      images of each TMJ by one observer. Presence and location of intra-articular
      fluid were evaluated on both standard T2W and new TSE images. Image quality was
      scored on a 3 point-scale by one observer. RESULTS: The net image acquisition
      time for one plane was 2 min with the new TSE sequence compared with
      approximately 5-10 min for T1W and 4 min for T2W. The new sequence provided
      equivalent diagnostic information to a combination of T1W CSE for disc position
      and contour and bone contour and T2W TSE sequence for joint fluid. CONCLUSIONS:
      The examination time for MRI of the TMJ can be considerably reduced with the new
      fast TSE pulse sequence without compromising image quality.

PMID- 11313736
TI  - Continuous radiographic visualization of the mandibular nutrient canals.
AB  - The continuous radiographic appearance of the course of mandibular nutrient
      canals (NC), originating from the incisive branch of the inferior alveolar
      neurovascular bundle bilaterally, showing anastomoses and terminating in the
      interdental area of the anterior teeth, is reported for the first time.

PMID- 11313739
TI  - XLMR genes: update 2000.
AB  - This is the sixth edition of the catalogue of XLMR genes, ie X-linked genes whose
      malfunctioning causes mental retardation. The cloning era is not yet concluded,
      actually much remains to be done to account for the 202 XLMR conditions listed in
      this update. Many of these may eventually prove to be due to mutations in the
      same gene but the present number of 33 cloned genes falls surely short of the
      actual total count. It is now clear that even small families or individual
      patients with cytogenetic rearrangements can be instrumental in pinning down the
      remaining genes. DNA chip technology will hopefully allow (re)screening large
      numbers of patients for mutations in candidate genes or testing the expression
      levels of many candidate genes in informative families. Slowly, our knowledge of
      the structure and functioning of the proteins encoded by these genes is beginning
      to cast some light on the biological pathways required for the normal development
      of intelligence. Correlations between the molecular defects and the phenotypic
      manifestations are also being established. In order to facilitate the exchange of
      existing information and to allow its timely update, we prepared the first
      edition of the XLMR database (available at
      http://homepages.go.com/~xlmr/home.htm) and invite all colleagues, expert in the
      field, to contribute with their experience.

PMID- 11313740
TI  - Maternal repression of the human GRB10 gene in the developing central nervous
      system; evaluation of the role for GRB10 in Silver-Russell syndrome.
AB  - The GRB10 gene encodes a growth suppressor and maps to human chromosome 7p11.2
      p13. Maternal duplication (matdup) of this region has recently been associated
      with Silver-Russell syndrome (SRS), which is characterised by pre- and postnatal
      growth restriction, craniofacial dysmorphism and lateral asymmetry. Maternal
      uniparental disomy for chromosome 7 (mUPD7) occurs in approximately 7% of SRS
      patients. Exposure of a recessive allele due to isodisomy has been ruled out in
      five mUPD7 cases, suggesting genomic imprinting as the basis for disease.
      Assuming SRS patients with matdup of 7p11.2-p13 and mUPD7 share a common
      aetiology, this would implicate a maternally expressed gene from this interval,
      which is involved in growth inhibition. Murine Grb10 was identified as a
      maternally expressed gene by subtractive hybridisation using normal and
      androgenetic mouse embryos. Grb10 maps to the homologous region of proximal mouse
      chromosome 11, for which mUPD incurs reduced birthweight. A role for GRB10 in SRS
      was evaluated by determining its imprinting status in multiple human foetal
      tissues using expressed polymorphisms, and by screening the coding region for
      mutations in 18 classic non-mUPD7 SRS patients. Maternal repression of GRB10 was
      observed specifically in the developing central nervous system including brain
      and spinal cord, with biallelic expression in peripheral tissues. This is in
      contrast to mouse Grb10, and represents the first example of opposite imprinting
      in human and mouse homologues. While a role for GRB10 in mUPD7 SRS cases can not
      be ruled out on the basis of imprinting status, no mutations were identified in
      the patients screened.

PMID- 11313741
TI  - Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association
      with neuroaxonal dystrophy?
AB  - Two new individuals with alpha-NAGA deficiency are presented. The index patient,
      3 years old, has congenital cataract, slight motor retardation and secondary
      demyelinisation. Screening of his sibs revealed an alpha-NAGA deficiency in his 7
      year-old healthy brother who had no clinical or neurological symptoms. Both sibs
      are homozygous for the E325K mutation, the same genotype that was found in the
      most severe form of alpha-NAGA deficiency presenting as infantile neuroaxonal
      dystrophy. Thus, at the age of 7 years the same genotype of alpha-NAGA may
      present as a 'non-disease' (present healthy case) and can be associated with the
      vegetative state (the first two patients described with alpha-NAGA deficiency).
      The clinical heterogeneity among the 11 known individuals with alpha-NAGA
      deficiency is extreme, with a 'non-disease' (two cases) and infantile neuroaxonal
      dystrophy (two cases) at the opposite sides of the clinical spectrum. The broad
      spectrum is completed by a very heterogeneous group of patients with various
      degrees of epilepsy/behavioural difficulties/psychomotor retardation (four
      patients) and a mild phenotype in adults without overt neurological
      manifestations who have angiokeratoma and clear vacuolisation in various cell
      types (three cases). These observations are difficult to reconcile with a
      straightforward genotype-phenotype correlation and suggest that factors or genes
      other than alpha-NAGA contribute to the clinical heterogeneity of the 11 patients
      with alpha-NAGA deficiency.

PMID- 11313743
TI  - Analysis of the genotypes and phenotypes of 37 unrelated patients with inherited
      factor VII deficiency.
AB  - Severe inherited factor VII (FVII) deficiency is a rare autosomal recessive
      disorder with a poor relationship between FVII coagulant activity and bleeding
      tendency. Both clinical expression and mutational spectrum are highly variable.
      We have screened for mutations the FVII gene of 37 unrelated patients with a FVII
      coagulant activity less than 5% of normal pooled plasmas. The nine exons with
      boundaries and the 5' flanking region of the FVII gene were explored using a
      combination of denaturing gradient gel electrophoresis and direct DNA sequencing.
      This strategy allowed us to characterise 68 out of the 74 predicted FVII mutated
      alleles. They corresponded to a large panel of 40 different mutations. Among
      these, 18 were not already reported. Genotypes of the severely affected patients
      comprised, on both alleles, deleterious mutations which appeared to be related to
      a total absence of activated FVII. We suggest that this absence of functional
      FVII can explain the severe clinical expression. Whether a small release of FVII
      is sufficient to initiate the coagulation cascade and to prevent the expression
      of a severe phenotype, requires further investigations.

PMID- 11313742
TI  - Patterns of inter- and intra-group genetic diversity in the Vlax Roma as revealed
      by Y chromosome and mitochondrial DNA lineages.
AB  - Previous genetic studies, supported by linguistic and historical data, suggest
      that the European Roma, comprising a large number of socially divergent
      endogamous groups, may be a complex conglomerate of founder populations. The
      boundaries and characteristics of such founder populations and their relationship
      to the currently existing social stratification of the Roma have not been
      investigated. This study is an attempt to address the issues of common vs
      independent origins and the history of population fissioning in three Romani
      groups that are well defined and strictly endogamous relative to each other.
      According to linguistic classifications, these groups belong to the Vlax Roma,
      who account for a large proportion of the European Romani population. The
      analysis of mtDNA sequence variation has shown that a large proportion of
      maternal lineages are common to the three groups. The study of a set of Y
      chromosome markers of different mutability has revealed that over 70% of males
      belong to a single lineage that appears unique to the Roma and presents with
      closely related microsatellite haplotypes and MSY1 codes. The study unambiguously
      points to the common origins of the three Vlax groups and the recent nature of
      the population fissions, and provides preliminary evidence of limited genetic
      diversity in this young founder population.

PMID- 11313744
TI  - Premature termination mutations in exon 3 of the SMN1 gene are associated with
      exon skipping and a relatively mild SMA phenotype.
AB  - Autosomal recessive spinal muscular atrophy (SMA) is a common motor neuron
      disease caused by absence or mutation in the survival motor neuron (SMN1) gene.
      SNM1 and a nearly identical copy, SMN2, encode identical proteins, but SMN2 only
      produces a little full length protein due to alternative splicing. The level of
      functional SMN protein and the number of SMN2 genes correlate with the clinical
      phenotype ranging from severe to very mild. Here, we report on premature
      termination mutations in SMN1 exon 3 (425del5 and W102X) which induce skipping of
      the mutated exon. The novel nonsense mutation W102X was detected in two patients
      with a relatively mild phenotype who had only two copies of the SMN2 gene, a
      number that has previously been found associated with the severe form of SMA. We
      show that the shortened transcripts are translated into predicted in frame
      protein isoforms. Aminoglycoside treatment suppressed the nonsense mutation in
      cultured cells and abolished exon skipping. Fibroblasts from both patients show a
      high number of nuclear structures containing SMN protein (gems). These findings
      suggest that the protein isoform lacking the exon 3 encoded region contributes to
      the formation of the nuclear protein complex which may account for the milder
      clinical phenotype.

PMID- 11313745
TI  - A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC
      contig, a partial transcript map and 15 new repeat polymorphisms in a tumour
      suppressor region.
AB  - Chromosomal region 11q22-q23 is a frequent target for deletion during the
      development of many solid tumour types, including breast, ovary, cervix, stomach,
      bladder carcinomas and melanoma. One of the most commonly deleted subregions
      contains the SDHD gene, which encodes the small subunit of cytochrome b (cybS) in
      mitochondrial complex II (succinate-ubiquinone oxidoreductase). Germline
      mutations in SDHD cause hereditary paraganglioma type 1 (PGL1), and suggest a
      tumour suppressor role for cybS. We present a high-resolution physical map
      spanning SDHD, covered by 19 YACs and 20 BACs. An approximate 1.1-Mb gene-rich
      region around SDHD is spanned by a complete BAC contig. Twenty-six new STSs are
      developed from the BAC clone ends. In addition to the discovery and
      characterisation of 15 new simple tandem repeat polymorphisms, we provide
      integrated positional information for 33 ESTs and known genes, including
      KIAA1391, POU2AF1 (OBF1), PPP2R1B, CRYAB, HSPB2, DLAT, IL-18, PTPS, KIAA0781 and
      KAIA4591, which is mapped by NotI site cloning. We describe full-length
      transcript sequence for PPP2R1B, encoding the protein phosphatase 2A regulatory
      subunit A beta isoform. We also discover a processed pseudogene for USA-CYP, a
      cyclophilin associated with U4/U6 snRPNs, and a novel gene, DDP2, encoding a
      mitochondrial protein similar to the X-linked deafness-dystonia protein, which is
      juxtaposed 5'-to-5' to SDHD. This map will help assess this gene-rich region in
      PGL and in other common tumours.

PMID- 11313747
TI  - PCAP is the major known prostate cancer predisposing locus in families from south
      and west Europe.
AB  - To date four prostate cancer predisposing loci have been mapped: HPC1 (Hereditary
      Prostate Cancer 1) on 1q24-25, PCaP (Predisposing for Cancer Prostate) on 1q42.2
      43, CAPB (Cancer Prostate and Brain) on 1p36, and HPCX on Xq27-28. We examined
      evidence for linkage to those loci in 64 families from south and west Europe.
      Genotyping of three (six for PCaP) markers encompassing the candidate regions
      were performed on 221 individuals including 159 affected patients. The resulting
      data were analysed using both parametric and non parametric linkage methods. No
      significant evidence of linkage to HPC1, CAPB, or HPCX was found either in the
      whole population or when pedigrees were stratified according to criteria specific
      to each locus. By contrast, results in favour of linkage to PCaP locus were
      observed with maximum multipoint NPL and HLOD scores of 2.8 (P = 0.0026) and 2.65
      respectively. Homogeneity analysis performed with multipoint LOD scores gave an
      estimated proportion of families with linkage to this locus up to 50%.
      Particularly, families with an earlier age at diagnosis (< or = 65-years-old)
      contributed significantly to the evidence of linkage with a maximum multipoint
      NPL score of 2.03 (P = 0.024). Those results suggest that PCaP is the most
      frequent known locus predisposing to hereditary prostate cancer cases from
      families from south and west Europe.

PMID- 11313746
TI  - The impact of genotyping error on family-based analysis of quantitative traits.
AB  - Errors in genotyping can substantially influence the power to detect linkage
      using affected sib-pairs, but it is not clear what effect such errors have on
      quantitative trait analyses. Here we use Monte Carlo simulation to examine the
      influence of genotyping error on multipoint vs two-point analysis, variable map
      density, locus effect size and allele frequency in quantitative trait linkage and
      association studies of sib-pairs. The analyses are conducted using variance
      components methods. We contrast the effects of error on quantitative trait
      analyses with those on the affected sib-pair design. The results indicate that
      genotyping error influences linkage studies of affected sib pairs more severely
      than studies of quantitative traits in unselected sibs. In situations of modest
      effect size, 5% genotyping error eliminates all supporting evidence for linkage
      to a true susceptibility locus in affected pairs, but may only result in a loss
      of 15% of linkage information in random pairs. Multipoint analysis does not
      suffer substantially more than two-point analysis; for moderate error rates (<
      5%), multipoint analysis with error is more powerful than two-point with no
      error. Map density does not appear to be an important factor for linkage
      analysis. QTL association analyses of common alleles are reasonably robust to
      genotyping error but power can be affected dramatically with rare alleles.

PMID- 11313748
TI  - Attempts to detect retrotransposition and de novo deletion of Alus and other
      dispersed repeats at specific loci in the human genome.
AB  - Dispersed repeat elements contribute to genome instability by de novo insertion
      and unequal recombination between repeats. To study the dynamics of these
      processes, we have developed single DNA molecule approaches to detect de novo
      insertions at a single locus and Alu-mediated deletions at two different loci in
      human genomic DNA. Validation experiments showed these approaches could detect
      insertions and deletions at frequencies below 10(-6) per cell. However, bulk
      analysis of germline (sperm) and somatic DNA showed no evidence for genuine
      mutant molecules, placing an upper limit of insertion and deletion rates of 2 x
      10(-7) and 3 x 10(-7), respectively, in the individuals tested. Such re
      arrangements at these loci therefore occur at a rate lower than that detectable
      by the most sensitive methods currently available.

PMID- 11313749
TI  - Maternally inherited deafness associated with a T1095C mutation in the mDNA.
AB  - Hearing loss is a relatively frequent defect in children with a genetic or
      predisposition basis in about 50% of cases. Mitochondrial DNA (mtDNA)-associated
      disorder often present with sensorineural hearing loss (SNHL) either in isolation
      or as a part of a multisystem disorder in adults but the frequency in pediatric
      cases is unknown. We analysed deafness-related mtDNA mutations in 80 deaf
      children to assess the relative frequency of alterations in childhood-onset SNHL.
      In 16 patients in whom maternal inheritance was possible, we screened for new
      mutations likely to affect mitochondrial protein synthesis. In one child we
      detected a novel mutation (T1095C) in the 12S rRNA gene. This mutation fulfils
      the suggested criteria for definition of a disease-related nucleotide variant. No
      mutations were found in other patients. Although we cannot exclude the presence
      of still undefined new mtDNA mutations, our data suggest that mtDNA defect are
      not common in childhood-onset SNHL.

PMID- 11313750
TI  - Genotype-phenotype correlations in Wolf-Hirschhorn syndrome.

PMID- 11313751
TI  - On the origin and frequency of the 35delG allele in GJB2-linked deafness in
      Europe.

PMID- 11313752
TI  - Brain studies of mouse models for neurogenetic disorders using in vivo magnetic
      resonance imaging (MRI).
AB  - Magnetic resonance imaging (MRI) is a technique commonly used to detect neural
      abnormalities in routine clinical practice. It is perhaps less well known that
      the technique can be adapted to measure various anatomical and physiological
      features of small laboratory rodents. This review focuses on the potential of the
      MRI technique to image the brain of (transgenic) mouse models for neurological
      diseases, and aims to introduce these exciting new technological developments to
      the non-specialist reader.

PMID- 11313753
TI  - Different types of repeat expansion in the TATA-binding protein gene are
      associated with a new form of inherited ataxia.
AB  - A novel neurological syndrome has recently been described to be associated with
      an expanded polyglutamine domain. The expansion results from partial duplication
      within the TATA-binding protein (TBP). By investigation of 604 sporadic and
      familial cases with various forms of neurological syndromes and 157 unaffected
      individuals, we found repeat expansions in the TBP in four patients of two
      families with autosomal dominant inheritance of ataxia, dystonia, and
      intellectual decline. Two different genotypes for the repetitive sequence could
      be demonstrated which led to elongated polyglutamine stretches between 50 and 55
      residues, whereas normal alleles with 27 to a maximum of 44 glutamine residues
      were found in this study. The expansion to 50 or more glutamine residues results
      in a pathological phenotype and confirms the report of a new polyglutamine
      disease.

PMID- 11313754
TI  - A novel locus for autosomal dominant, non-syndromic hearing impairment (DFNA18)
      maps to chromosome 3q22 immediately adjacent to the DM2 locus.
AB  - Investigating a large German pedigree with non-syndromic hearing impairment of
      early onset and autosomal dominant mode of inheritance, linkage to known DFNA
      loci was excluded and in a subsequent genomic scan the phenotype was mapped to a
      10-cM interval on chromosome 3q22; a maximum two-point lod score of 3.77 was
      obtained for the marker D3S1292. The new locus, DFNA18, is excluded from
      neighbouring deafness loci, DFNB15 and USH3, and it overlaps with the recently
      described DM2/PROMM locus. As hearing loss has been described as one feature of
      the PROMM phenotype, the DFNA18 gene might also be responsible for hearing loss
      in DM2/PROMM.

PMID- 11313755
TI  - A Rett syndrome patient with a ring X chromosome: further evidence for skewing of
      X inactivation and heterogeneity in the aetiology of the disease.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, characterised by
      regression of development in young females. Recently, mutations in the MECP2 gene
      were found to be present in 80% of sporadic cases, but in much lower frequency (<
      30%) among familial cases. Several reports claim that the pattern of X chromosome
      inactivation (XCI) relates to the penetrance of RTT; in some cases skewed XCI is
      seen in Rett patients, and in others it is observed among normal carriers. We
      present here a case of RTT with a 46,X,r(X) in which complete skewed inactivation
      of the ring was demonstrated. Further, no mutations were found in the MECP2 gene
      present on the intact X. Our data, in conjunction with two previously published
      cases of X chromosome abnormalities in RTT, indicate that X chromosome
      rearrangements are sporadically associated with RTT in conjunction with extreme
      skewing of X inactivation. Based on our case and reported data, we discuss the
      evidence for a second X-linked locus for RTT associated with lower penetrance,
      and a different pattern of XCI, than for MECP2. This would result in a larger
      proportion of phenotypically normal carrier women transmitting the mutation for
      this putative second locus, and account for the minority of sporadic and majority
      of familial cases that are negative for MECP2 mutations.

PMID- 11313757
TI  - Mitochondrial DNA analysis of the putative heart of Louis XVII, son of Louis XVI
      and Marie-Antoinette.
AB  - According to official historiography, the 10-year-old Louis XVII died in the
      Temple of Paris on June 8, 1795. However, public rumour spread the theory that
      Louis XVII escaped and that his descendants would be alive today. One such
      putative 'Louis XVII' was Carl Wilhelm Naundorff, who died in 1845 in Delft (the
      Netherlands). Comparative mitochondrial DNA (mtDNA) analysis gave evidence that
      his remains could not be identified as those of Louis XVII. In the present study,
      mtDNA analysis was performed on the heart of the young boy who died in the prison
      of Paris in 1795. In order to obtain the strongest evidence possible, two
      laboratories independently analysed the heart. The results showed that the
      consensus mtDNA sequence of the heart was identical to that of the maternal
      relatives of Louis XVII.

PMID- 11313756
TI  - MECP2 mutations in Danish patients with Rett syndrome: high frequency of
      mutations but no consistent correlations with clinical severity or with the X
      chromosome inactivation pattern.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder, which almost exclusively
      affects girls, who, after an initial period of apparently normal development,
      display gradual loss of speech and purposeful hand use, gait abnormalities and
      stereotypical hand movements. In the year 2000, mutations in the gene for the
      methyl CpG binding protein 2, MECP2, have been identified in 35-80% of the
      patients in three different studies. We have identified 15 different MECP2
      mutations in 26 of 30 Danish RTT patients. The mutations included five novel
      mutations (one point mutation, three smaller deletions involving identical
      regions in the gene, and one duplication). In contrast to the point mutations and
      the duplication, which all affect the methyl binding domain or the
      transcriptional repressing domain, the three overlapping deletions are clustered
      in the 3' end of the gene. We found no consistent correlation between the type of
      mutation and the clinical presentation of the patient or the X-inactivation
      pattern in peripheral blood. Our high mutation detection rate, compared to two of
      the previous studies, underscores the importance of the inclusion criteria of the
      patients and supports that MECP2 is the most important, if not the only, gene
      responsible for RTT.

PMID- 11313759
TI  - Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing
      the skin disease striate palmoplantar keratoderma.
AB  - The adhesive proteins of the desmosome type of cell junction consist of two types
      of cadherin found exclusively in that structure, the desmogleins and
      desmocollins, coded by two closely linked loci on human chromosome 18q12.1.
      Recently we have identified a mutation in the DSG1 gene coding for desmoglein 1
      as the cause of the autosomal dominant skin disease striate palmoplantar
      keratoderma (SPPK) in which affected individuals have marked hyperkeratotic bands
      on the palms and soles. In the present study we present the complete exon-intron
      structure of the DSG1 gene, which occupies approximately 43 kb, and intron
      primers sufficient to amplify all the exons. Using these we have analysed the
      mutational changes in this gene in five further cases of SPPK. All were
      heterozygotic mutations in the extracellular domain leading to a truncated
      protein, due either to an addition or deletion of a single base, or a base change
      resulting in a stop codon. Three mutations were in exon 9 and one in exon 11,
      both of which code for part of the third and fourth extracellular domains, and
      one was in exon 2 coding for part of the prosequence of this processed protein.
      This latter mutation thus results in the mutant allele synthesising only 25 amino
      acid residues of the prosequence of the protein so that this is effectively a
      null mutation implying that dominance in the case of this mutation was caused by
      haploinsufficiency. The most severe consequences of SPPK mutations are in regions
      of the body where pressure and abrasion are greatest and where desmosome function
      is most necessary. SPPK therefore provides a very sensitive measure of desmosomal
      function.

PMID- 11313758
TI  - A single mutated MEFV allele in Israeli patients suffering from familial
      Mediterranean fever and Behcet's disease (FMF-BD).
AB  - Although familial Mediterranean fever (FMF) is an autosomal recessive disorder,
      preliminary partial mutation analysis suggested that about 60% of FMF patients,
      who also suffer from Behcet's disease (FMF-BD), have only a single mutated FMF
      gene (MEFV). In this study, the possibility that patients with FMF-BD may indeed
      be carriers of a single mutated MEFV is further analysed. The presence of
      mutations in the coding region of MEFV of eight patients with FMF-BD,
      representing six families with 47 members, was determined by sequencing. A
      possible role for the non-carrier chromosome and for BD in the expression of FMF
      in patients with a single mutated MEFV allele was determined by analysing the
      association between these variables and the presence of FMF in heterozygous kin.
      Sequence analysis revealed that all eight patients had indeed only one mutation
      in the coding region of MEFV. The patients' non-carrier chromosomes converged
      into three different MEFV haplotypes and were shared by heterozygous unaffected
      kin in five of six families. BD was found in 10 of 11 carriers with FMF vs one of
      16 carriers without FMF (P < 0.001). These results suggest that FMF may be
      expressed in individuals harbouring only one coding mutation in MEFV. The
      findings argue against a role for the non-carrier chromosome in the induction of
      FMF, and suggest that the FMF phenotype in this cohort was associated with the
      simultaneous presence of BD. These findings may mirror a more generalised rule,
      that FMF may be precipitated in carriers of a single mutated FMF gene by factors
      unrelated to the other MEFV allele.

PMID- 11313760
TI  - The R482Q lamin A/C mutation that causes lipodystrophy does not prevent nuclear
      targeting of lamin A in adipocytes or its interaction with emerin.
AB  - Most pathogenic missense mutations in the lamin A/C gene identified so far cause
      autosomal-dominant dilated cardiomyopathy and/or Emery-Dreifuss muscular
      dystrophy. A few specific mutations, however, cause a disease with remarkably
      different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan
      type), which mainly affects adipose tissue. We have prepared lamin A with a known
      FPLD mutation (R482Q) by in vitro mutagenesis. Nuclear targeting of lamin A in
      transfected COS cells, human skeletal muscle cells or mouse adipocyte cell
      cultures (pre- and post-differentiation) was not detectably affected by the
      mutation. Quantitative in vitro measurements of lamin A interaction with emerin
      using a biosensor also showed no effect of the mutation. The results show that
      the loss of function of R482 in lamin A/C in FPLD does not involve loss of
      ability to form a nuclear lamina or to interact with the nuclear membrane
      protein, emerin.

PMID- 11313761
TI  - Parental mosaicism of JAG1 mutations in families with Alagille syndrome.
AB  - The Alagille syndrome (AGS), a congenital disorder affecting liver, heart,
      skeleton and eye in association with a typical face, is an autosomal dominant
      disease with nearly complete penetrance and variable expression. AGS is caused by
      mutations in the developmentally important JAG1 gene. In our mutation screening,
      where 61 mutations in JAG1 were detected, we identified five cases where
      mosaicism is present. Our results point to a significant frequency of mosaicism
      for JAG1 mutations in AGS of more than 8.2%. Because mosaicism may be associated
      with a very mild phenotype, the appropriate diagnosis of AGS and consequently the
      determination of the recurrence risk can be complicated.

PMID- 11313763
TI  - Sensorineural hearing loss and the incidence of Cx26 mutations in Austria.
AB  - A clinical evaluation and Cx26 mutation analysis was performed in 92 consecutive
      patients with sensorineural hearing loss in order to delineate the spectrum of
      genetically caused hearing loss. Among patients of Austrian origin, 53% were
      classified with hereditary hearing loss. Cx26 mutations were found in 26% of NSHL
      patients (40% of familial vs 18% of sporadic cases). The mutation 35delG
      accounted for 52.8% of all presumed GJB2 disease alleles. The second most
      frequent mutation was L90P (16.7%) having been reported with a prevalence of 0.7
      3.5% in other populations. Three novel mutations were found. The novel mutation,
      R143Q, was associated with dominant high-frequency hearing loss. Pseudodominant
      transmission of NSHL was seen in four families with Cx26 mutations. A mutation
      35delG carrier rate of 0.9% was observed among 672 controls from West-Austria.
      Cx26 mutations were found associated with mild to profound, and with asymmetric
      hearing impairment.

PMID- 11313762
TI  - Monosomy for the most telomeric, gene-rich region of the short arm of human
      chromosome 16 causes minimal phenotypic effects.
AB  - We have examined the phenotypic effects of 21 independent deletions from the
      fully sequenced and annotated 356 kb telomeric region of the short arm of
      chromosome 16 (16p13.3). Fifteen genes contained within this region have been
      highly conserved throughout evolution and encode proteins involved in important
      housekeeping functions, synthesis of haemoglobin, signalling pathways and
      critical developmental pathways. Although a priori many of these genes would be
      considered candidates for critical haploinsufficient genes, none of the deletions
      within the 356 kb interval cause any discernible phenotype other than alpha
      thalassaemia whether inherited via the maternal or paternal line. These findings
      contrast with previous observations on patients with larger (> 1 Mb) deletions
      from the 16p telomere and therefore address the mechanisms by which monosomy
      gives rise to human genetic disease.

PMID- 11313764
TI  - Parental origin of de novo MECP2 mutations in Rett syndrome.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively
      in females as sporadic cases. Recently, DNA mutations in the MECP2 gene have been
      detected in approximately 70% of patients with RTT. To explain the sex-limited
      expression of RTT, it has been suggested that de novo X-linked mutations occur
      exclusively in male germ cells resulting therefore only in affected daughters. To
      test this hypothesis, we have analysed 19 families with RTT syndrome due to MECP2
      molecular defects. In seven informative families we have found by DHPLC a
      nucleotide variant which could be used to differentiate between the maternal and
      the paternal allele. In each subject investigated from these families, we have
      amplified specifically each allele and sequenced allele-specific PCR products to
      identify the allele bearing the mutation as well as the parental origin of each X
      chromosome. This approach allowed us to determine the parental origin of de novo
      mutations in all informative families. In five cases, the de novo MECP2 mutations
      have a paternal origin and in the two other cases a maternal origin. In all
      transitions at CpG, the de novo mutation observed was of paternal origin. The
      high frequency of male germ-line transmission of the mutation (71% of RTT
      informative cases) is consistent with a predominant occurrence of the disease in
      females.

PMID- 11313766
TI  - Molecular characterisation of 34 patients with biotinidase deficiency ascertained
      by newborn screening and family investigation.
AB  - This study characterises the spectrum of biotinidase mutations in 21 patients (17
      families) with profound biotinidase deficiency (BD) and 13 unrelated patients
      with partial BD using a denaturing gradient gel electrophoretic mutation
      screening and selective sequencing approach. In 29 from 30 unrelated families we
      found biallelic mutations including four common mutations, D444H (frequency
      23.3%), G98:d7i3(20.0%), Q456H(20.0%), T532M (15.0%) and nine rare mutations
      (V62M, R157H, A171T+D444H, C423W, D543H, L279W, N172S, V109G, 12236G-A) with
      frequencies less than 5.0%. Only three profound BD patients with
      G98:d7i3/G98:d7i3 and Q456H/Q456H genotypes and residual biotinidase activities
      of 0.0%, and 0.9% of normal activity developed clinical symptoms before biotin
      supplementation at 8 weeks of age. All other patients remained asymptomatic
      within the first months of life or even longer without treatment. Two patients
      homozygous for the frameshift mutation G98:d7i3 had no measurable residual enzyme
      activity. Twelve patients with partial BD had the D444H mutation in at least one
      allele. We conclude that, based on mutation analysis and biochemical examinations
      of the enzyme, it is currently not clearly predictable whether an untreated
      patient will develop symptoms or not, although it seems that patients with
      activities lower than 1% are at a high risk for developing symptoms of the
      disease early in life.

PMID- 11313765
TI  - Saturating density of STSs (1/6 kb) in a 1.1 Mb region on 3q28-q29: a valuable
      resource for cloning of disease genes.
AB  - We have fine mapped 29 ESTs of Genemap'99 to YACs and radiation hybrids covering
      8 cM of the chromosomal region of 3q28-q29. Focusing on the genetic interval of
      approximately 1 Mb between markers D3S3669 and D3S3562 we established a sequence
      ready PAC contig which covers the OPA1 locus containing the gene causing
      autosomal dominant optic atrophy (ADOA; OMIM*165500). The fidelity of the contig
      was increased by the generation of 181 PAC end sequences, 84 of which resulted in
      PCR-able STSs. Sequence content evaluation of the PAC ends by BLAST analysis
      identified two novel ESTs localising to the OPA1 crucial interval.

PMID- 11313767
TI  - A molecular genetic service for diagnosing individuals with familial
      hypercholesterolaemia (FH) in the United Kingdom.
AB  - A genetic diagnostic service for familial hypercholesterolaemia (FH) has been
      established over the last 4 years in the Clinical Molecular Genetics Laboratory
      at Great Ormond Street Hospital for Children NHS Trust (GOSH), London. In total
      there have been 368 referrals; 227 probands and 141 family members, which have
      come from a number of lipid clinics and from general practitioners. FH is caused
      by mutations in the low-density lipoprotein receptor gene (LDLR) and these are
      analysed by SSCP, DNA sequencing and direct assays. The clinically
      indistinguishable disorder, familial defective apolipoprotein B100 (FDB) is
      caused by one of three mutations in the apolipoprotein B100 gene (APOB) which are
      analysed by direct assays. Mutations predicted to be pathogenic were found in 76
      probands, 67 in LDLR (23 previously undescribed) and nine in APOB. The mutation
      detection rate was 53% in paediatric probands, 32% in adults with a 'definite' FH
      diagnosis (tendon xanthoma positive) and 14% in adults with a 'possible' FH
      diagnosis (tendon xanthoma negative). The predicted loss of sensitivity that
      would result from reducing the number of exons tested has been assessed, and a
      molecular screening strategy suitable for UK patients is proposed. A similar
      strategy may be useful for other countries where genetic heterogeneity results in
      a wide mutation spectrum for FH.

PMID- 11313768
TI  - Organization of the mevalonate kinase (MVK) gene and identification of novel
      mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic
      fever syndrome.
AB  - Mevalonic aciduria (MA) and hyperimmunoglobulinaemia D and periodic fever
      syndrome (HIDS) are two autosomal recessive inherited disorders both caused by a
      deficient activity of the enzyme mevalonate kinase (MK) resulting from mutations
      in the encoding MVK gene. Thus far, disease-causing mutations only could be
      detected by analysis of MVK cDNA. We now describe the genomic organization of the
      human MVK gene. It is 22 kb long and contains 11 exons of 46 to 837 bp and 10
      introns of 379 bp to 4.2 kb. Three intron-exon boundaries were confirmed from
      natural splice variants, indicating the occurrence of exon skipping. Sequence
      analysis of 27 HIDS and MA patients confirmed all previously reported genotypes
      based on cDNA analysis and identified six novel nucleotide substitutions
      resulting in missense or nonsense mutations, providing new insights in the
      genotype/phenotype relation between HIDS and MA.

PMID- 11313770
TI  - Alu insertion polymorphisms and the genetic structure of human populations from
      the Caucasus.
AB  - An analysis of 8 Alu insertion loci (ACE, TPA25, PV92, APO, FXIIIB, D1, A25, B65)
      has been carried out in six populations from the Caucasus, including Indo
      European-speaking Armenians; Altaic-speaking Azerbaijanians; North Caucasian
      speaking Cherkessians, Darginians, and Ingushians; and South Caucasian
      (Kartvelian)-speaking Georgians. The Caucasus populations exhibit low levels of
      within-population variation and high levels of between-population
      differentiation, with the average Fst value for the Caucasus of 0.113, which is
      almost as large as the Fst value of 0.157 for worldwide populations. Maximum
      likelihood tree and principal coordinate analyses both group the Caucasus
      populations with European populations. Neither geographic nor linguistic
      relationships appear to explain the genetic relationships of Caucasus
      populations. Instead, it appears as if they have been small and relatively
      isolated, and hence genetic drift has been the dominant influence on the genetic
      structure of Caucasus populations.

PMID- 11313769
TI  - Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and
      periodic fever syndrome.
AB  - Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is an autosomal
      recessive inflammatory disorder characterised by recurrent episode of fever
      associated with lymphadenopathy, abdominal distress, joint involvement and skin
      lesions. We recently demonstrated that mutations in the mevalonate kinase gene
      (MVK) are associated with HIDS. Direct DNA sequencing was done to screen the
      entire coding region of MVK in 25 unrelated patients with HIDS. Mutations were
      detected in the coding region of the gene including 11 missense mutations, one
      deletion, the absence of expression of one allele, as well as three novel
      polymorphisms. Seven of these mutations are novel. The large majority of the
      patients were compound heterozygotes for two mutations. Of these, V377I (G-->A)
      is the most common mutation occurring in 20 unrelated patients and was found to
      be associated with I268T in six patients. Mutations were associated with a
      decrease of mevalonate kinase (MK) (ATP:mevalonate 5-phosphotransferase, EC
      2.7.I.36) enzymatic activity but not as profound as in mevalonic aciduria, a
      syndrome also caused by a deficient activity of MK. In HIDS the mutations are
      located all along the protein which is different from mevalonic aciduria where MK
      mutations are mainly clustered to a same region of the protein. On the basis of
      this study, we propose that the diagnostic screen of MVK in HIDS should be first
      directed on V377I and I268T mutations. Three patients are also described to
      illustrate the genotypic and phenotypic overlap with mevalonic aciduria.

PMID- 11313771
TI  - An alpha1-antitrypsin enhancer polymorphism is a genetic modifier of pulmonary
      outcome in cystic fibrosis.
AB  - Lung disease is the direct cause of death in over 90% of cystic fibrosis (CF)
      patients. Excess neutrophil elastase is an important determinant of pulmonary
      disease in CF. alpha1-antitrypsin (AAT), also known as alpha1-proteinase
      inhibitor (alpha1PI) is a major modulator of elastase activity. We investigated
      the hypothesis that an enhancer polymorphism in the AAT gene would contribute to
      pulmonary prognosis in CF. Respiratory function, chest X-ray scores, bacterial
      colonisation and infective exacerbation were assessed to evaluate pulmonary
      disease severity in the CF group. Sixteen patients were found to have the 1237A
      allele, and 108 the more frequent G allele. Contrary to expectation, the patients
      with the 1237A allele were found to have better indices of pulmonary disease
      progression than those without, as indicated by less change in X-ray score
      (1237A: 0.2+/-0.1; 1237G: 1.2+/-0.1; P = 0.002) and fewer infective exacerbations
      (1237A: 2.8+/-0.6; 1237G: 4.6+/-0.3; P = 0.03) over the preceding 2 years. Also,
      a higher proportion of the 1237A (25%) than the 1237G (6.5%) were not colonised
      by Pseudomonas Aeruginosa (P = 0.04). Prospective monitoring of infections for a
      further 2 years confirmed a lesser propensity to infection in patients with the
      1237A allele. These trends were also observed in a tightly matched sub-set of CF
      genotypes of similar age and sex, thus confirming that these effects were
      independent of the CF genotype. These results indicate that this AAT enhancer
      polymorphism is associated with better pulmonary prognosis in CF. Though the
      number of CF patients with the polymorphism is small, and these data need to be
      confirmed in larger studies, they suggest that a cautious approach should perhaps
      be taken to treatment of CF patients with supplemental AAT.

PMID- 11313772
TI  - Is mitochondrial DNA depletion involved in Alzheimer's disease?
AB  - Several studies have suggested that mitochondrial metabolism disturbances and
      mitochondrial DNA (mtDNA) abnormalities may contribute to the progression of the
      pathology of Alzheimer's disease (AD). In this study we have investigated whether
      the amount of mtDNA is modified in different brain regions (cerebellum,
      hippocampus and frontal cortex) of confirmed AD necropsies and in blood of living
      AD patients. We used a real-time PCR method to analyse the mtDNA relative
      abundance in brain regions from 12 AD and seven controls and from a group of
      blood samples (17 living AD patients and 11 controls). MtDNA from blood samples
      together with hippocampus and cerebellum brain areas did not show differences
      between controls and AD. However, AD patients showed a 28% decrease in the amount
      of mtDNA in the frontal cortex when compared to controls for this specific area.
      Since frontal cortex is a severely affected region in AD, our results support the
      hypothesis that mitochondrial defects may play a role in the pathogenesis of AD.

PMID- 11313773
TI  - A placental diploid cell line is not essential for ongoing trisomy 13 or 18
      pregnancies.
AB  - Viable trisomy 13 or 18 pregnancies may be supported by the presence of a diploid
      cell line, confined to the outer layer of the placenta (cytotrophoblast). To
      establish the presence of diploid cells we investigated five random biopsies from
      placentas of trisomy 13 (n = 8) and trisomy 18 cases (n = 6) of newborn infants
      and terminated pregnancies by means of fluorescence in situ hybridisation on
      interphase nuclei (n = 100). In 12 of these 14 placentas (including all five
      liveborns) 80% or more of the analysed nuclei showed three spots, suggestive of
      the presence of a full trisomy. In the other two placentas (both cases of trisomy
      18) mosaicism was detected at most investigated sites. Thus, in contrast with
      earlier studies, these results show that a significant diploid cell line present
      in the placenta, confined to the trophoblast, is not a pre-requisite for
      intrauterine survival in the investigated cases.

PMID- 11313774
TI  - Haplotypes vs single marker linkage disequilibrium tests: what do we gain?
AB  - The genetic dissection of complex diseases represents a formidable challenge for
      modern human genetics. Recently, it has been suggested that linkage
      disequilibrium (LD) based methods will be a powerful approach for delineating
      complex disease genes. Most proposed LD test statistics search for association
      between a single marker and a putative trait locus. However, the power of a
      single marker association test may suffer because LD information contained in
      flanking markers is ignored. Intuitively, haplotypes (which can be regarded as a
      collection of ordered markers) may be more powerful than individual, unorganised
      markers. In this study, we derive the analytical tools based on standard chi
      square statistics to directly investigate and compare the power between
      multilocus haplotypes and single marker LD tests. More specifically, novel
      formulas are obtained in order to calculate expected haplotype frequencies of
      unlimited size. This study demonstrates that the use of haplotypes can
      significantly improve the power and robustness of mapping disease genes.
      Additionally, we detail how the power of haplotype based association tests are
      affected by important population genetic parameters such as the genetic distance
      between markers and disease locus, mode of disease inheritance, age of trait
      causing mutation, frequency of associated marker allele, and level of initial LD.
      Finally, published data from the Hereditary Hemochromatosis disease region is
      used to illustrate the utility of haplotypes.

PMID- 11313775
TI  - The family based association test method: strategies for studying general
      genotype--phenotype associations.
AB  - With possibly incomplete nuclear families, the family based association test
      (FBAT) method allows one to evaluate any test statistic that can be expressed as
      the sum of products (covariance) between an arbitrary function of an offspring's
      genotype with an arbitrary function of the offspring's phenotype. We derive
      expressions needed to calculate the mean and variance of these test statistics
      under the null hypothesis of no linkage. To give some guidance on using the FBAT
      method, we present three simple data analysis strategies for different
      phenotypes: dichotomous (affection status), quantitative and censored (eg, the
      age of onset). We illustrate the approach by applying it to candidate gene data
      of the NIMH Alzheimer Disease Initiative. We show that the RC-TDT is equivalent
      to a special case of the FBAT method. This result allows us to generalise the RC
      TDT to dominant, recessive and multi-allelic marker codings. Simulations compare
      the resulting FBAT tests to the RC-TDT and the S-TDT. The FBAT software is freely
      available.

PMID- 11313776
TI  - The mitochondrial DNA mutation T12297C affects a highly conserved nucleotide of
      tRNA(Leu(CUN)) and is associated with dilated cardiomyopathy.
AB  - Mitochondrial DNA (mtDNA) mutations have been causally linked with
      cardiomyopathies, both dilated (DCM) and hypertrophic. We identified the T12297C
      mutation in the mtDNA-tRNA(Leu(CUN)) of a 36-year-old male patient diagnosed with
      DCM. The mutation was heteroplasmic, with high amount (88%) of mutant DNA in the
      myocardium, and was absent in normal (n = 120) and disease (n = 150) controls. It
      affects a highly conserved nucleotide (adjacent to the anticodon triplet) that
      allows the phospho-ribose backbone to turn and form the loop. The potential
      pathological role of T12297C mutation is further supported by its recent
      identification in another unrelated Italian family with DCM associated with
      endocardial fibroelastosis. In the variable loop of the same tRNA, our patient
      also carried the A12308G transition that is debated as pathological mutation or
      neutral polymorphism in progressive external ophthalmoplegia: the two defects
      could exert a synergistic effect on the tRNA structure and function. The
      endomyocardial biopsy study showed abnormal ring-like mitochondria and occasional
      cytochrome c oxydase negative myocytes. Overall, the heteroplasmy, the highly
      conserved position of the mutated nucleotide, the absence of the mutation in
      large series of diseased and normal controls, and the cardiac mitochondrial
      changes support a causative link of the mutation with the disease.

PMID- 11313778
TI  - Clinical research results with dl1520 (Onyx-015), a replication-selective
      adenovirus for the treatment of cancer: what have we learned?
AB  - Replication-selective microbial agents hold promise as a novel cancer treatment
      platform. dl1520 (Onyx-015), an E1B-55 kD gene-deleted adenovirus, was the first
      such genetically engineered agent to be tested in humans. Over 200 cancer
      patients have been treated to date on over 10 clinical trials (phases I-III). The
      virus was generally well-tolerated at doses of up to 2 x 10(12) particles by
      intratumoral, intraperitoneal, hepatic arterial and intravenous administration;
      no maximally tolerated doses were identified by any route of administration.
      Viral replication was tumor-selective, and was documented after administration by
      all routes; replication was generally transient (<10 days), however, and was
      variable depending on tumor histology. single agent efficacy has been limited to
      date (0-14% local tumor regression rates). in combination with chemotherapy,
      however, encouraging antitumoral activity has been demonstrated. these clinical
      research results demonstrate the potential of this novel treatment platform, as
      well as the hurdles to be overcome. novel replication-selective agents with
      improved potency are needed.

PMID- 11313777
TI  - 3rd International Meeting on Single Nucleotide Polymorphism and Complex Genome
      Analysis: SNPs: 'some notable progress'.
AB  - Fervent activities for the collection and exploitation of single nucleotide
      polymorphism (SNP) data continue, amid concerns about their real utility. The
      desire to understand complex disease aetiology remains a key driving force for
      this activity. Recent developments provided a level of cautious optimism not seen
      in previous International Meetings on Single Nucleotide Polymorphism and Complex
      Genome Analysis. The 3rd such meeting, held 8-11 September 2000 in Taos, New
      Mexico, covered research on technologies for SNP scoring, analytical tools for
      using SNPs to map disease genes, examples from researchers using SNPs for
      specific disease studies, and databases and tools for facilitating these
      activities. Studies of human history, and a range of studies upon model organisms
      were also represented. Whilst the transition from technology oriented work
      (methods, discovery, etc.) to successful biological application is occurring
      relatively slowly, a clear trend in this direction is now apparent, and it will
      surely gain momentum in future months and years. Many fundamental properties of
      SNPs remain unknown, and many other basic questions are still unanswered, but the
      field is moving forward on all necessary fronts, promising exciting advances just
      around the corner.

PMID- 11313779
TI  - CL22 - a novel cationic peptide for efficient transfection of mammalian cells.
AB  - Condensing peptide-DNA complexes have great potential as nonviral agents for gene
      delivery. To date, however, such complexes have given transfection activities
      greatly inferior to adenovirus and somewhat inferior to cationic lipid-DNA
      complexes, even for cell lines and primary cells in vitro. We report here the
      identification of a novel condensing peptide, CL22, which forms DNA complexes
      that efficiently transfect many cell lines, as well as primary dendritic and
      endothelial cells. We report studies with sequence and structure variants that
      define some properties of the peptide that contribute to efficient transfection.
      We demonstrate that the superior transfection activity of CL22 compared with
      other DNA condensing peptides is conferred at a step after uptake of the
      complexes into cells. We show that CL22-DNA complexes have transfection activity
      that is at least equivalent to the best available nonviral agents.

PMID- 11313780
TI  - Expression of vhs and VP16 during HSV-1 helper virus-free amplicon packaging
      enhances titers.
AB  - Recently developed helper virus-free methods of herpes simplex virus (HSV)
      amplicon vector packaging provide stocks that are virtually devoid of the
      cytotoxic component normally associated with traditional helper virus-based
      packaging methods. These approaches involve cotransfection of amplicon plasmid
      DNA with either a five-cosmid set or a bacterial artificial chromosome (BAC) that
      contains the HSV genome without its cognate pac signals. Helper virus-free
      amplicon packaging produces low-titer stocks (<10(5) expressing particles/ml)
      that exhibit a high frequency of pseudotransduction. In an effort to enhance
      amplicon titers, we introduced in trans a genomic copy of the virion host shutoff
      (vhs) protein-encoding gene UL41 into both cosmid- and BAC-based packaging
      strategies. Cotransfection of this plasmid with the amplicon and packaging
      reagents results in a 10-fold higher amplicon titer, and stocks that do not
      exhibit the pseudotransduction phenomenon. To further enhance packaging
      efficiency, the HSV transcriptional activator VP16 was introduced into packaging
      cells 1 day before the packaging components. Pre-loading of packaging cells with
      VP16 led to an additional enhancement of amplicon titers, an effect that did not
      occur in the absence of vhs. Increased helper virus-free amplicon titers
      resulting from these modifications will make in vivo transduction experiments
      more feasible.

PMID- 11313781
TI  - Sustained expression of human apo A-I following adenoviral gene transfer in mice.
AB  - Elevation of HDL cholesterol, following adenoviral apolipoprotein A-I (apo A-I)
      gene transfer, may delay or revert ischemic cardiovascular disease, provided
      transgene expression is persistent. The choice of promoter may have significant
      impact on persistence of transgene expression. Human apo A-I expression was
      compared after adenoviral gene transfer with a cytomegalovirus promoter (CMV)
      driven construct (AdCMV/A-I.gA-I) and with a construct (AdA-I.gA-I.4xapoE)
      containing the endogenous 256 bp apo A-I promoter (A-I), the genomic human apo A
      I DNA (gA-I) and 4 human apo E enhancers (4xapoE) in three different mouse
      strains: C57BL/6, Balb/c and Fvb. After gene transfer with 5 x 10(8) p.f.u. of
      AdCMV/A-I.gA-I, human apo A-I expression was observed for 35 days in C57BL/6
      mice, but declined below 1 mg/dl within 14 days both in Balb/c and Fvb mice, due
      to a strong humoral immune response against human apo A-I. In contrast, after
      transfer with AdA-I.gA-I.4xapoE, human apo A-I expression persisted for 6 months
      in all three strains and no antibodies against human apo A-I occurred in Fvb or
      Balb/c mice. Human apo A-I transgene DNA level 35 days after transfer with AdA
      I.gA-I.4xapoE was 4.6- to 5.5-fold higher than with AdCMV/A-I.gA-I. CMV promoter
      attenuation occurred in all three strains, but promoter attenuation was not
      observed in any strain after transfer with AdA-I.gA-I.4xapoE. In conclusion, gene
      transfer with AdA-I.gA-I.4xapoE is associated with absence of an immune response
      against human apo A-I, improved transgene DNA persistence and absence of promoter
      shut-off, resulting in human apo A-I expression for up to 6 months in three
      different mouse strains. Possibly, the absence of human apo A-I expression in
      antigen-presenting cells with the liver-specific apo A-I promoter containing
      construct abrogated the immune response against human apo A-I in Balb/c and Fvb
      mice.

PMID- 11313782
TI  - Recombinant DNA vaccines protect against tumors that are resistant to recombinant
      vaccinia vaccines containing the same gene.
AB  - Antigen-specific cancer immunotherapy involves the delivery of tumor-associated
      antigen to the host for the generation of tumor-specific immune responses and
      antitumor effects. We hypothesized that different delivery systems may influence
      the pattern of antigen-specific immune response and the outcome of antitumor
      effect. We therefore evaluated recombinant vaccinia virus and naked DNA for the
      generation of antigen-specific immune responses and antitumor effects. We
      previously found that recombinant vaccinia and naked DNA vaccines containing the
      chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7
      expressing tumor cells (TC-1). In this study, we performed a head-to-head
      comparison of optimized delivery of Sig/E7/LAMP-1 vaccinia and DNA vaccines using
      dose-escalating tumor challenge. At a dose of 1 x 10(6) TC-1 cells per mouse,
      Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors,
      while Vac-Sig/E7/LAMP-1 protected only 40% of the mice. Furthermore, Sig/E7/LAMP
      1 DNA vaccines are capable of protecting against challenge with a more stringent
      subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial
      Sig/E7/LAMP-1 vaccinia vaccination. Immunological assays revealed that both
      vaccines induced comparable levels of CD8(+) T cell precursors and anti-E7
      antibody titers. Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific
      IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA
      induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors. We also
      found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia
      exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice
      in our tumor protection experiments. These results suggest that IL-4 may play a
      detrimental role in the antitumor effect mediated by vaccinia vaccines. Our
      findings suggested that DNA vaccines may provide better tumor protection than
      vaccinia vaccines employing the same gene, which may have implications in the
      future design of antigen-specific cancer immunotherapy.

PMID- 11313783
TI  - Connexin 26 enhances the bystander effect in HSVtk/GCV gene therapy for human
      bladder cancer by adenovirus/PLL/DNA gene delivery.
AB  - Herpes simplex thymidine kinase/ganciclovir (HSVtk/GCV) gene therapy has been
      used for the treatment of a variety of cancers. Its efficacy is enhanced by the
      bystander effect that helps overcome the delivery problems commonly observed in
      current gene therapy. Connexins encode proteins that produce gap junctions, which
      enable intercellular communication and the bystander effect. We previously
      demonstrated that decreased Cx 26 expression and loss of gap junctional
      intercellular communication were associated with human bladder cancer. To
      investigate the efficacy of the bystander effect in HSVtk/GCV gene therapy, the
      Cx 26 gene was introduced into UM-UC-3 and UM-UC-14 bladder cancer cell lines by
      an adenovirus poly-L-lysine conjugate using a multigenic expression plasmid that
      expressed both the HSVtk and Cx 26 genes. We found significantly increased
      cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx 26
      genes together compared with the cytotoxicity seen after introduction of the
      HSVtk gene and LacZ genes in vitro and in vivo. Cytotoxicity correlated with Cx
      26 expression and the induction of functional gap junctions. This study indicates
      that combination gene therapy with co-expression of the HSVtk and Cx 26 genes
      potentiates HSVtk/GCV gene therapy through the bystander effect.

PMID- 11313784
TI  - Anti-metastatic gene therapy utilizing subcutaneous inoculation of EC-SOD gene
      transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and
      3LL cells in mice.
AB  - We have previously reported that superoxide stimulates the motility of tumor
      cells and the administration of Cu-Zn superoxide dismutase (SOD) significantly
      suppresses metastasis. However, ideally, anti-metastatic therapy should be long
      lasting, systemically effective and have low toxicity. The half-life of Cu-Zn SOD
      in plasma is so short that it cannot provide long-lasting effects. Therefore, in
      this study we have developed a gene therapy in a mouse model utilizing
      extracellular SOD (EC-SOD), which is the most prevalent SOD isoenzyme in
      extracellular fluids. We retrovirally transfected fibroblasts (syngeneic) with
      the EC-SOD gene and established EC-SOD-secreting fibroblasts. Inoculation of EC
      SOD-secreting fibroblasts suppressed both artificial and spontaneous metastatic
      lung nodules in mouse metastasis models. These data indicate the feasibility of
      anti-metastatic gene therapy utilizing the EC-SOD gene.

PMID- 11313785
TI  - Investigation of RNA transcripts containing HIV-1 packaging signal sequences as
      HIV-1 antivirals: generation of cell lines resistant to HIV-1.
AB  - Based on the success of RNA decoy approaches using RRE and TAR sequences to
      inhibit HIV-1 replication, we studied the ability of HIV-1 packaging signal
      sequences to interfere with viral RNA encapsidation and formation of infectious
      particles. We made a variety of plasmid constructs in which the sequence context
      or number of repeats of the viral packaging signal was varied, and investigated
      the ability of these transcripts to inhibit replication of HIV-1 in stably
      transfected Jurkat T lymphocytes. We found that certain lines showed strong
      inhibition of HIV-1 replication, an effect that persisted at high input amounts
      of virus and significantly delayed viral replication for up to 4 weeks. An
      investigation of the mechanism of inhibition revealed that in these cell lines
      the packaging efficiency of the genomic HIV-1 transcript was unaffected. Further
      studies identified an antiviral effect on both HIV-1 and HIV-2 that did not
      correlate with decoy expression, and was substantially independent of CD4
      expression or cellular proliferative capacity. Study of these resistant cell
      lines may lead to new insights into mechanisms of inhibition of HIV-1
      replication.

PMID- 11313786
TI  - Enhancement of MSH receptor- and GAL4-mediated gene transfer by switching the
      nuclear import pathway.
AB  - Efficient nuclear delivery of plasmid DNA represents a major barrier in nonviral
      gene transfer. One approach has been to use DNA-binding proteins such as GAL4
      from yeast as DNA carriers with nuclear targeting properties. We recently showed,
      however, that GAL4 is inefficient in targeting DNA to the nucleus because its DNA
      binding and nuclear targeting activities are mutually exclusive, which relates to
      the fact that GAL4 nuclear import occurs via a novel pathway. Here, we 'switch'
      this pathway to a more conventional one by adding a modified poly-lysine to which
      an optimized nuclear targeting signal, based on that of the SV40 large T-antigen,
      is linked. We also use a chimeric GAL4-alpha-melanocyte stimulating hormone (MSH)
      fusion protein to enable gene transfer to cells expressing the MSH receptor.
      Switching the nuclear import pathway of the transfecting complex significantly
      enhances receptor-mediated gene transfer through enabling interaction with
      desired components of the cellular nuclear import machinery. The present study
      represents the first demonstration that nuclear targeting signals can enhance
      receptor-mediated gene delivery, the approaches having important relevance to
      research and clinical applications, such as in generating transgenic or knock-out
      animals, or in gene therapy.

PMID- 11313788
TI  - Nonviral in vivo gene delivery into tumors using a novel low volume jet-injection
      technology.
AB  - The jet-injection technology has developed as an applicable alternative to viral
      or liposomal gene delivery systems. In this study a novel, low-volume, 'high
      speed jet injector' hand-held system was used for the direct gene transfer of
      naked DNA into tumors. Lewis-lung carcinoma bearing mice were jet-injected with
      the beta-galactosidase (LacZ), the green fluorescence (GFP) or the human tumor
      necrosis factor alpha (TNF-alpha) gene carrying vector plasmids. The animals
      received five jet injections into the tumor at a pressure of 3.0 bar, delivering
      3--5 microl plasmid DNA (1 microg DNA/microl in water) per single jet injection.
      The jet injection of DNA leads to a widespread expression pattern within tumor
      tissues with penetration depths of 5--10 mm. Analysis of tumor cryosections
      revealed moderate LacZ or GFP expression at 48 h and strong reporter gene
      expression 72 h and 96 h after jet injection. The simultaneous jet injection of
      the TNF-alpha and LacZ carrying vectors demonstrated efficient expression and
      secretion of both the cytokine, as well as LacZ expression within the tumor 24 h,
      48 h, 72 h, 96 h and 120 h after jet injection. These studies demonstrate the
      applicability of jet injection for the efficient in vivo gene transfer into
      tumors for nonviral gene therapy of cancer using minimal amounts of naked DNA.

PMID- 11313789
TI  - Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat
      and rabbit hindlimb ischemia models: preclinical study for treatment of
      peripheral arterial disease.
AB  - Hepatocyte growth factor (HGF) exclusively stimulates the growth of endothelial
      cells without replication of vascular smooth muscle cells, and acts as a survival
      factor against endothelial cell death. Recently, a novel therapeutic strategy for
      ischemic diseases using angiogenic growth factors to expedite and/or augment
      collateral artery development has been proposed. We have previously reported that
      intra-arterial administration of recombinant HGF induced angiogenesis in a rabbit
      hindlimb ischemia model. In this study, we examined the feasibility of gene
      therapy using HGF to treat peripheral arterial disease rather than recombinant
      therapy, due to its disadvantages. Initially, we examined the transfection of
      'naked' human HGF plasmid into a rat hindlimb ischemia model. Intramuscular
      injection of human HGF plasmid resulted in a significant increase in blood flow
      as assessed by laser Doppler imaging, accompanied by the detection of human HGF
      protein. A significant increase in capillary density was found in rats
      transfected with human HGF as compared with control vector, in a dose-dependent
      manner (P < 0.01). Importantly, at 5 weeks after transfection, the degree of
      angiogenesis induced by transfection of HGF plasmid was significantly greater
      than that caused by a single injection of recombinant HGF. As an approach to
      human gene therapy, we also employed a rabbit hindlimb ischemia model as a
      preclinical study. Naked HGF plasmid was intramuscularly injected in the ischemic
      hindlimb of rabbits, to evaluate its angiogenic activity. Intramuscular injection
      of HGF plasmid once on day 10 after surgery produced significant augmentation of
      collateral vessel development on day 30 in the ischemia model, as assessed by
      angiography (P < 0.01). Serial angiograms revealed progressive linear extension
      of collateral arteries from the origin stem artery to the distal point of the
      reconstituted parent vessel in HGF-transfected animals. In addition, a
      significant increase in blood flow was assessed by a Doppler flow wire and the
      ratio in blood pressure of the ischemic limb to the normal limb was observed in
      rabbits transfected with HGF plasmid as compared with rabbits transfected with
      control vector (P < 0.01). Overall, intramuscular injection of naked human HGF
      plasmid induced therapeutic angiogenesis in rat and rabbit ischemic hindlimb
      models, as potential therapy for peripheral arterial disease.

PMID- 11313790
TI  - Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA
      flap.
AB  - Retroviral vectors have become the primary tool for gene delivery into
      hematopoietic cells, including T lymphocytes. Lentiviral vectors offer an
      advantage over Moloney murine leukemia virus (MuLV) vectors because of their
      ability to translocate across an intact nuclear membrane and integrate into the
      genome of nonproliferating cells. We have recently demonstrated that a central
      strand displacement event, controlled by the central polypurine tract (cPPT) and
      the central termination sequence (CTS), results in the formation of a central DNA
      flap which acts as a cis-determinant of HIV-1 genome nuclear import. Here, we
      show that insertion of this DNA determinant in a classical lentiviral vector
      resulted in a significantly higher level of transduction in activated T cells (51
      +/- 12.7% versus 15 +/- 1.4%). CD4(+) and CD8(+) T cells were transduced at
      equivalent levels. Importantly, freshly isolated T cells stimulated only during
      the 12-h transduction period could be efficiently transduced with this new flap
      containing lentiviral vector, but not with the parental lentiviral vector nor an
      MuLV vector. Transgene expression in the flap-containing lentiviral vector, under
      the control of either an internal cytomegalovirus or the elongation factor-1
      alpha (EF1 alpha) promoter, was significant and expression remained elevated in
      resting T cells. Thus, this system allows stable expression of transgenes in T
      lymphocytes following a short ex vivo transduction protocol.

PMID- 11313791
TI  - Adenovirus-mediated transfer of p53 and p16(INK4a) results in pancreatic cancer
      regression in vitro and in vivo.
AB  - Pancreatic cancer has a very poor prognosis. Current chemotherapy and
      radiotherapy regimens are only moderately successful. The tumour suppressor genes
      p53 and p16(INK4a)encode cell cycle regulatory proteins that are important
      candidates for gene replacement therapy. Over 80% of pancreatic adenocarcinoma
      cases lack detectable p16 protein while over 60% contain mutated p53 protein. We
      used replication-deficient recombinant adenoviruses to reintroduce wild-type p16
      and p53 into pancreatic cancer cells in vitro and into subcutaneous pancreatic
      tumours in an animal model to determine the effect on tumour growth. Significant
      growth inhibition was observed in all five human pancreatic cell lines with these
      viruses (P < 0.002) compared with similar control viruses expressing either
      luciferase or beta-galactosidase. G1 arrest was observed in all cell lines 72 h
      after infection with Adp16. Infection with Adp53 caused significant levels of
      apoptosis (P < 0.004). Apoptosis was also observed to a lesser degree (P < 0.03)
      with the Adp16 vector. Subcutaneous pancreatic tumours, generated in nu-nu mice
      demonstrated significant growth suppression following injection of Adp53, Adp16
      and a combination of both Adp53 and Adp16 (P < 0.0001). These results show that
      transfer of wild-type p53 and p16 produces significant growth suppression of
      pancreatic cancer in vitro and in vivo.

PMID- 11313792
TI  - Direct in vivo transfection of antisense Fas-ligand reduces tumor growth and
      invasion.
AB  - The expression of Fas ligand (FasL) by tumor cells has been reported to have
      multiple, conflicting effects on tumor growth. The majority of the data support
      the theory that FasL expressing tumor cells evade immune surveillance by killing
      T cells expressing Fas. However, the role of the humoral immune-blockade by FasL
      expressing tumor cells has not been assessed. Using immune-competent mice, we
      observed that FasL expressing tumor cells reduced the antitumor antibody
      production together with the T and B cell content of the spleen in these mice.
      Further, to determine if the expression of FasL in the environment of the tumor
      suppresses the humoral antitumor immune response and influences tumor growth, a
      mouse model lacking T cells was used. To assess whether a local reduction of FasL
      could reduce tumor progression, a plasmid encoding antisense FasL cDNA was
      delivered directly into a growing tumor (SW620 colon carcinoma). Intratumoral
      delivery of the plasmid was able to transfect tumor cells, stromal cells, and
      peritumoral muscle cells. This antisense FasL tumor tissue transfection persisted
      for at least 25 days, produced a systemic decrease in soluble FasL, and resulted
      in a 50% reduction in the rate of tumor growth when compared with tumor tissue of
      the control groups. These results suggest that direct transfection of antisense
      FasL cDNA impairs FasL translation in tumor and stromal cells, and can inhibit
      tumor progression by impairing the FasL-mediated, stromal cell-assisted, tumor
      counter-attack.

PMID- 11313793
TI  - Eradication of murine brain tumors by direct inoculation of concentrated high
      titer-recombinant retrovirus harboring the herpes simplex virus thymidine kinase
      gene.
AB  - Implantation of retrovirus-producing cells within a tumor has been demonstrated
      to eliminate malignant brain tumors effectively in animal models. In our previous
      study, the implantation of high-titer retrovirus-producing fibroblasts into
      tumors resulted in highly efficient transduction in vivo. The transduced glioma
      cells migrated far from the implantation site, potentiating the induction of the
      remarkable bystander effect. It is also possible, however, that the implantation
      of murine fibroblast-derived virus-producing cells may induce an immune response
      in patients. In this study, we prepared retroviruses carrying the herpes simplex
      virus thymidine kinase (HTK) gene with titers of 1.4--2.5 x 10(11) colony-forming
      units (c.f.u.)/ml, and stereotactically inoculated only 3 microl of the HTK
      bearing retroviruses into the brain tumors of mice. Following repetitive
      ganciclovir (GCV) intraperitoneal injection, effective killing of glioma cells in
      the mouse brain was observed. The transduction efficiency was nearly as high as
      that observed for the implantation of high-titer retrovirus-producing
      fibroblasts. Eighty percent of brain tumor-bearing mice were completely cured by
      our treatment protocol using concentrated HTK-harboring retroviruses. Our results
      suggest that repeated inoculations of high-titer retroviruses carrying the HTK
      gene followed by GCV treatment may be a promising strategy for the clinical
      treatment of malignant gliomas.

PMID- 11313794
TI  - Efficacy of adenoviral TNF alpha antisense is enhanced by a macrophage specific
      promoter.
AB  - Macrophage-derived TNF alpha is a critical mediator of inflammation and
      destruction in diseases such as rheumatoid arthritis and Crohn's disease. These
      studies were undertaken to develop an effective adenovirus-based strategy to
      specifically suppress TNF alpha in primary human macrophages. A variety of
      promoters and LTRs were evaluated for effective expression in the macrophage cell
      line RAW 264.7. The CMV promoter and the Visna LTR were the most strongly
      expressed and were therefore used to drive the expression of TNF alpha antisense
      fragments. In transient transfection assays, the antisense fragment terminating
      at the 3' end of the first exon (216 bp) was superior to the others (70 and 750
      bp), when expressed under the control of either the CMV promoter or the Visna
      LTR. Adenoviral vectors expressing the 216 bp TNF alpha antisense fragment,
      controlled by the CMV promoter or the Visna LTR, were both effective at
      suppressing LPS-induced TNF alpha secretion by primary human macrophages.
      However, the Visna LTR was more effective not only at suppressing LPS-induced TNF
      alpha secretion, but also IL-6, which is highly sensitive to TNF alpha secretion.
      These results demonstrate that effective, specific, suppression of TNF alpha in
      macrophages is possible, employing a directed antisense approach and a promoter
      system that is highly efficient in human macrophages.

PMID- 11313795
TI  - Suicide gene therapy for premalignant disease: a new strategy for the treatment
      of intraepithelial neoplasia.
AB  - The potential of gene therapy to treat premalignant disease or recurrent cancer
      has not been investigated. The goal of the present investigation was to explore
      the efficacy of pro-drug-mediated, suicide gene therapy as a strategy to treat
      incipient neoplasia in stratified squamous epithelium. To test this strategy, a
      tissue model of premalignancy was generated by mixing normal human keratinocytes
      (NHK) that express the bacterial cytosine deaminase gene (CD) with premalignant
      keratinocytes which have been genetically marked with the bacterial gene for beta
      galactosidase (II-4-beta-gal) in skin-like organotypic cultures. Preliminary
      studies in monolayer cultures demonstrated that CD-transduced NHK (NHK/CD)
      efficiently expressed the transgene and deaminated the pro-drug 5-fluorocytosine
      (5FC) to the toxic product 5-fluorouracil (5FU). The capacity of NHK/CD to kill
      II-4-beta-gal cells through bystander effect was assayed in both submerged
      culture and in the organotypic model of premalignancy. In submerged cultures, it
      was found that CD-mediated killing of II-4-beta-gal cells did not require cell
      cell contact and that the LD(50) of 5FC for efficient bystander killing of II-4
      beta-gal was 0.5 mM. When this concentration of pro-drug was used in organotypic
      cultures, a significant number of dysplastic II-4-beta-gal cells were eliminated
      from the tissue. Bystander killing of II-4-beta-gal cells was related to the
      number of NHK/CD present. These findings demonstrated that potentially malignant
      keratinocytes could be eliminated from a dysplastic tissue through activation of
      pro-drug and killing of adjacent cells through the bystander effect. By
      establishing an in vitro model to eliminate premalignant cells using suicide gene
      therapy, these studies provide a new approach for the treatment of incipient
      cancer as it develops, thereby preventing invasive disease.

PMID- 11313796
TI  - Improved post-transcriptional processing of an MDR1 retrovirus elevates
      expression of multidrug resistance in primary human hematopoietic cells.
AB  - We describe the functional analysis of a novel retroviral vector, SF91m3, which
      was designed for improved expression of the in vivo selectable marker, multidrug
      resistance 1 gene (MDR1), in hematopoietic cells. SF91m3 combines several
      promising features. The vector backbone lacks viral coding sequences and AUG
      start codons 5' of the MDR1 cDNA. A point mutation of a cryptic splice acceptor
      of the MDR1 cDNA increases the probability of transferring an intact provirus.
      The titer of a PG13 packaging cell clone containing a single proviral integration
      is high (>2 x 10(6) particles/ml from frozen stocks of serum-free vector
      harvests). Human hematopoietic cells transduced with SF91m3 reliably express MDR1
      before and after passage through NOD/SCID mice, as shown by quantitative PCR and
      efflux assays with rhodamine 123 or Hoechst 33342. Finally, SF91m3 mediates
      resistance to escalated doses of cytotoxic agents, as shown by survival and
      differentiation of transduced colony-forming cells in the presence of colchicine
      at 48 ng/ml (>10 x IC(50)). Thus, SF91m3 may represent an interesting candidate
      for future trials addressing the safety and utility of MDR1 gene transfer;
      moreover, this study demonstrates that sequence alterations improving post
      transcriptional processing of retroviral vectors have a substantial impact for
      gene expression in hematopoietic cells.

PMID- 11313797
TI  - Creation of a new transgene cloning site near the right ITR of Ad5 results in
      reduced enhancer interference with tissue-specific and regulatable promoters.
AB  - Tissue-specific transgene expression is a valuable research tool and is of great
      importance in delivering toxic gene products with adenovirus vectors to tumors.
      Limiting cytotoxic gene expression to the target cells is highly desirable. While
      a number of successful applications of tissue- and tumor-specific gene expression
      using Ad vectors has been reported, cloning of some promoters into Ad vectors
      resulted in modulation or loss of tissue specificity. This phenomenon is likely
      the result of the interaction of E1A enhancer (and possibly other Ad sequences)
      with the promoter cloned in the E1 region. We have compared performance
      parameters of prostate-specific and tet-regulatable promoters in plasmids
      containing the terminal repeat sequences of Ad5 with or without the E1A enhancer.
      Subsequently, adenoviral vectors were constructed containing identical expression
      units either in the E1 region or near the right ITR, and tested in several cell
      lines. Here, we report that promoters placed near the right ITR of Ad5 retain
      higher selectivity and lower background expression in both plasmid and adenovirus
      vectors. We confirm that the E1A enhancer can interfere with the desired activity
      of nearby promoters, and describe an alternative transgene insertion site for
      construction of Ad vectors.

PMID- 11313798
TI  - Pulmonary cytokine responses associated with PEI-DNA aerosol gene therapy.
AB  - Pulmonary gene therapy with nonviral vectors delivered by instillation or
      intravenously has typically been associated with co-induction of cytokine
      responses attributed to the CpG motifs in the bacterial plasmid. Alternative
      delivery systems are being developed to circumvent the cytokine responses to the
      plasmid. Aerosol delivery of polyethylenimine--DNA (PEI-DNA) complexes leads to
      localized, high levels of transgene expression in the lungs. In this study, we
      show that PEI-DNA aerosol delivery is also associated with induction of tumor
      necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the lung
      and bronchoalveolar lavage fluid (BALF). However, there is no increase in the
      serum levels of these cytokines. The levels of these cytokines peak at 5--8 h
      after aerosol exposure for lung tissue, and at 24 h for BALF. However, the levels
      detected are much lower than those observed when PEI-DNA complexes, guanidinium-
      cholesterol: dioleoylphosphatidyl--ethanolamine liposome--DNA (BGTC:DOPE--DNA)
      complexes or 1,2-dioleoyl-sn-glycero-3-trimethylammonium--propane-
      cholesterol:DNA (DOTAP-Chol:DNA) complexes were delivered intravenously. Also,
      the lung cytokine levels were higher when BGTC:DOPE--DNA complexes were delivered
      by aerosol to the mice. Although the mechanism remains to be elucidated, the data
      suggest that aerosol exposure to PEI--DNA complexes can achieve high levels of
      transgene expression in the lungs without inducing high levels of cytokine
      responses.

PMID- 11313800
TI  - Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain
      tumor.
AB  - A retroviral vector constructed from the murine leukemia virus (MLV) can only
      express transgenes in cells undergoing mitosis, indicating its suitability as a
      delivery vehicle for cancer gene therapy. However, the transduction efficiency
      (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells
      was found to be unsatisfactory. Recently, several research groups have
      demonstrated the feasibility of a retroviral vector pseudotyped with a vesicular
      stomatitis virus G (VSV-G) protein. In this study, the potential of VSV-G
      pseudotyped MLV-based retrovirus was examined as a delivery vehicle in a variety
      of human cancer cells including brain tumor cells in vitro and in vivo. The
      transduction efficiency of the 293T/G/GP/LacZ retrovirus in cell culture was
      superior in most cancer cells, particularly in brain tumor cells, compared with
      that of other retroviruses, such as PA317- or PG13-derived. The relative growth
      rate and phosphatidylserine expression level on the plasma membrane of target
      cells mainly influenced the transduction efficiency of VSV-G pseudotyped
      retrovirus, which suggested that both the relative growth rate and
      phosphatidylserine expression level were major determinants of TE. Furthermore,
      293T/G/GP/LacZ could efficiently transduce human cancer cells regardless of the
      presence of chemical additives, whereas in other retroviruses, cationic chemical
      additives such as polybrene or liposomes were essential during virus infection.
      Finally, an average of 10% gene expression was routinely obtained exclusively in
      the tumor mass when 293T/G/GP/LacZ concentrated by simple ultracentrifugation was
      directly administrated to pre-established brain tumors in animal models (U251-N
      nu/nu mice or C6 Wistar rats). All told, the present study suggests that the VSV
      G pseudotyped retrovirus is a suitable vector for brain tumor gene therapy.

PMID- 11313799
TI  - Genetic heterogeneity in the toxicity to systemic adenoviral gene transfer of
      interleukin-12.
AB  - Despite the efficacy of IL-12 in cancer experimental models, clinical trials with
      systemic recombinant IL-12 showed unacceptable toxicity related to endogenous
      IFNgamma production. We report that systemic administration of a recombinant
      adenovirus encoding IL-12 (AdCMVmIL-12) has a dramatically different survival
      outcome in a number of mouse pure strains over a wide range of doses. For
      instance at 2.5 x 10(9) p.f.u., systemic AdCMVmIL-12 killed all C57BL/6 mice but
      spared all BALB/c mice. Much higher IFNgamma concentrations in serum samples of
      C57BL/6 than in those from identically treated BALB/c were found. Causes for
      heterogeneous toxicity can be traced to differences among murine strains in the
      levels of gene transduction achieved in the liver, as assessed with adenovirus
      coding for reporter genes. In accordance, IL-12 serum concentrations are higher
      in susceptible mice. In addition, sera from C57BL/6 mice treated with AdCMVmIL-12
      showed higher levels of IL-18, a well-known IFNgamma inducer. Interestingly,
      lethal toxicity in C57BL/6 mice was abolished by administration of blocking anti
      IFNgamma mAbs and also by simultaneous depletion of T cells, NK cells, and
      macrophages. These observations together with the great dispersion of IFNgamma
      produced by human PBMCs upon in vitro stimulation with IL-12, or infection with
      recombinant adenovirus encoding IL-12, suggest that patients might also show
      heterogeneous degrees of toxicity in response to IL-12 gene transfer.

PMID- 11313801
TI  - Tumour-specific therapeutic adenovirus vectors: repression of transgene
      expression in healthy cells by endogenous p53.
AB  - Approximately 50% of human tumours lack functional p53 suppressor protein. A
      promoter that is repressed by p53 in healthy cells could thus provide tumour
      specific gene expression for a huge subset of tumours. In this report we describe
      a double recombinant adenovirus vector, 'Ad.p53R', encoding a therapeutic gene
      that is indirectly repressed by endogenous wild-type p53. Ad.p53R contains two
      independent expression cassettes; (1) the E. coli nitroreductase gene (NTR)
      driven by the human hsp70 promoter containing LacI binding sites (hsp70lacO-NTR)
      and (2) a p53-inducible lac repressor gene (tkGC3-lacI). In p53 null cells
      (Hep3B), Ad.p53R directed the same level of NTR expression as Ad.p53NR which
      lacks the tkGC3-lacI cassette. Moreover, injection of SW480 xenografts (mutated
      p53) with Ad.p53R resulted in a clear inhibition of growth in response to the
      prodrug CB1954. In cells retaining wt p53 (HepG2 and primary human endothelial
      cells), Ad.p53R expressed significantly less NTR (approximately 70%) than
      Ad.p53NR. Ad.p53R administered by i.v. injection also produced significantly less
      NTR than Ad.p53NR in normal tissues in vivo. Finally, adenovirus infection per se
      of cultured HepG2 cells at low MOI induced p53 stabilisation suggesting that
      adenovirus-mediated gene delivery may contribute to p53-based selectivity.

PMID- 11313802
TI  - Combined CXC chemokine and interleukin-12 gene transfer enhances antitumor
      immunity.
AB  - It has been shown that intratumor administration of an adenovirus vector
      expressing IL-12 produces a potent T cell-mediated response that leads to
      significant tumor regression in a murine breast cancer model. IP-10 and MIG are
      CXC chemokines that recruit mononuclear cells in vivo. In addition to their
      chemotactic roles, IP-10 and MIG inhibit angiogenesis. We tested whether the
      addition of IP-10 or MIG may both enhance the antitumor immune response of IL-12
      through T cell recruitment and inhibit tumor growth through angiostasis.
      Adenovirus vectors expressing IP-10 or MIG and/or IL-12 were administered
      intratumorally in a murine model of mammary adenocarcinoma and fibrosarcoma.
      Administration of IP-10 or MIG in combination with IL-12 resulted in considerable
      tumor regression and increased survival time of tumor-bearing animals as compared
      with IP-10, MIG, IL-12 alone or control-treated animals, with the IP-10 IL-12
      combination being most effective. These results suggest augmenting the antitumor
      immune response and inhibiting tumor angiogenesis with adenoviral vectors
      expressing IP-10 in combination with IL-12 is a novel way to enhance tumor
      regression.

PMID- 11313803
TI  - Detection and measurement of in vitro gene transfer by gamma camera imaging.
AB  - The purpose of this work was to develop a high capacity method to image gene
      transfer to cancer cells growing as monolayers in cell culture plates. A
      sensitive and high capacity nuclear-imaging method for detection of gene transfer
      in vitro will allow rapid validation of vectors in different cell lines under
      various conditions. Human cancer cell lines (A-427 non-small cell lung, SKOV3.ip1
      ovarian, MDA-MB-468 breast, and BxPC-3 pancreatic) were infected with a
      replication-incompetent adenoviral vector encoding the human type 2 somatostatin
      receptor (Ad-hSSTr2). Expression of the hSSTr2 reporter protein in cells was
      detected by imaging an internalized 99mTc-labeled, hSSTr2 binding peptide (P2045,
      Diatide, Inc.). Imaging provided an accurate measure of internally bound 99mTc as
      evidenced by equivalence of results for imaging region of interest (ROI) analyses
      and gamma counter measurements. Internally bound 99mTc-P2045 was linearly
      correlated (R2 = 0.98) with the percentage of hSSTr2-positive cells following
      gene transfer. Excess P2045 blocked binding and internalization of the 99mTc
      P2045, indicating the specificity of the technique. Up to four 96-well plates
      could be imaged simultaneously, thereby demonstrating the high capacity of the
      system. This novel in vitro approach provides a new method to test enhanced gene
      transfer as new vectors are developed.

PMID- 11313804
TI  - Activation of peritoneal cells upon in vivo transfection with a recombinant
      alphavirus expressing GM-CSF.
AB  - In this study we determined the in vivo localization of recombinant proteins
      expressed by intraperitoneally (i.p.) injected recombinant Semliki Forest virus
      (SFV) particles. Subsequently, we investigated the influence of i.p. administered
      SFV particles encoding recombinant murine granulocyte-macrophage colony
      stimulating factor (rmGM-CSF) on intraperitoneal recruitment and activation of
      cells. Finally, the therapeutic effect of SFV-GM-CSF treatment on an i.p. growing
      ovarian tumor was determined. Intraperitoneal injections of recombinant SFV
      particles encoding the reporter protein luciferase resulted in a high level of
      luciferase activity in cells of the peritoneal lining and tumor cells in the
      peritoneal cavity. Low levels of luciferase activity were found in liver, spleen
      and lungs. Injection of SFV-GM-CSF particles resulted in a slight increase in the
      number of peritoneal macrophages and in a significant increase in the number of
      neutrophils. In contrast to multiple i.p. injections with commercially available
      recombinant GM-CSF, i.p. injected SFV-GM-CSF particles activated the macrophages
      to tumor cytotoxicity. Although treatment of tumor-bearing mice with SFV-GM-CSF
      particles did not result in prolonged survival, tumor growth was inhibited for 2
      weeks. Our findings indicate that macrophage-activating cytokines expressed by
      the efficient and safe recombinant SFV system when administered i.p. may provide
      an immunotherapeutic treatment modality additional to current chemotherapeutic
      treatment of intraperitoneally growing cancers.

PMID- 11313805
TI  - Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication
      selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase
      I trial.
AB  - Novel therapies are needed for locally advanced pancreatic carcinoma. ONYX-015
      (dl1520) is an E1B-55 kDa region-deleted adenovirus that selectively replicates
      in and lyses tumor cells with abnormalities in p53 function (eg gene mutation).
      We carried out a phase I dose escalation study of ONYX-015 in patients with
      unresectable pancreatic cancer. ONYX-015 was administered via CT-guided injection
      (n = 22 patients) or intraoperative injection (n = 1) into pancreatic primary
      tumors every 4 weeks until tumor progression. Interpatient dose escalation was
      carried out with at least three patients per dose level from 10(8) p.f.u. up to
      the 10(11) p.f.u. dose level (two patients treated at this dose). The majority of
      patients had abnormally low cellular immunity (CD4 counts and hypersensitivity
      skin testing). Injection of ONYX-015 into pancreatic carcinomas was well
      tolerated. Mild, transient pancreatitis was noted in only one patient. Dose
      escalation proceeded to the highest dose level. Neutralizing antibodies rose post
      treatment in all patients. After injection, ONYX-015 was detectable in the blood
      15 min later, but not between 1 and 15 days later. Viral replication was not
      documented, however, in contrast to trials in other tumor types. No objective
      responses were demonstrated. Intratumoral injection of an E1B-55 kDa region
      deleted adenovirus into primary pancreatic tumors was feasible and well-tolerated
      at doses up to 10(11) p.f.u. (2 x 10(12) particles), but viral replication was
      not detectable.

PMID- 11313806
TI  - Induction of ErbB-2/neu-specific protective and therapeutic antitumor immunity
      using genetically modified dendritic cells: enhanced efficacy by cotransduction
      of gene encoding IL-12.
AB  - Overexpression of ErbB-2/neu occurs in 20-30% of patients with breast cancer and
      indicates a poor prognosis. The presence of a detectable immune response to ErbB
      2/neu in some patients suggests that this oncogene may be a useful target for
      vaccine therapy. We evaluated whether genetic immunization using dendritic cells
      (DC) transduced ex vivo with an adenovirus expressing the ErbB-2/neu gene
      (AdNeuTK) could induce protective and therapeutic immunity against a breast tumor
      cell line overexpressing ErbB-2/neu. Subcutaneous (s.c.) immunization with the DC
      vaccine elicited protective immunity in an average of 60% of animals. CTL
      analysis demonstrated specific cytotoxic activity against breast tumor cells, as
      well as syngeneic fibroblasts transduced with AdNeuTK. In vivo depletion studies
      demonstrated both CD4+ and CD8+ T cells were required. In a therapeutic setting,
      immunization with the DC vaccines could cure mice with pre-established tumors and
      efficacy was further enhanced by cotransducing DCs with a vector expressing
      murine IL-12 (AdmIL-12). These studies support DC vaccines as a therapeutic
      strategy for human breast cancer, while emphasizing the importance of optimizing
      an immune response by combining tumor antigen presentation with immunostimulatory
      cytokines.

PMID- 11313807
TI  - Expansion of tropism of a feline parvovirus to target a human tumor cell line by
      display of an alpha(v) integrin binding peptide on the capsid.
AB  - The autonomous parvoviruses are small, non-enveloped, single strand DNA viruses.
      They occur in many species and they have oncolytic properties. We are modifying
      the capsid of feline panleukopenia virus (FPV), a parvovirus which normally
      infects feline cells, with the goal of targeting human tumor cells for potential
      cancer therapy. Using recombinant viruses transducing a luciferase reporter, we
      show that insertion of a cyclically constrained, integrin-binding peptide at an
      exposed position on the FPV capsid enables transduction of an alpha(v) integrin
      expressing human rhabdomyosarcoma cell line (Rh18A). These cells were not
      transduced by virus with the unmodified FPV capsid. Transduction of Rh18A was
      specifically inhibited by an alpha(v) integrin blocking antibody. However, other
      human tumor lines expressing alpha(v) integrins were not transduced by virus with
      either the modified or unmodified capsid. We conclude that modification of the
      FPV capsid to bind alpha(v) integrins can contribute to, but is not generally
      sufficient for, redirecting infection to human tumor cells. The permissiveness of
      Rh18A cells presumably involves additional factors unique to this line among
      various human cell lines tested.

PMID- 11313808
TI  - Combination suicide/cytokine gene therapy as adjuvants to a defective herpes
      simplex virus-based cancer vaccine.
AB  - We have used syngeneic, established bilateral subcutaneous tumor models to
      examine the antitumor activity of herpes simplex virus (HSV) vectors, including
      the induction of an immune response against non-inoculated distant tumors. In
      such a model with CT26 murine colon adenocarcinoma, unilateral intratumoral
      inoculation of replication-deficient HSV-1 tsK inhibited the growth of both the
      inoculated and noninoculated established tumors. To enhance this limited
      antitumor immune response, we generated a defective HSV vector, dvIL12-tk
      encoding both interleukin-12 (IL-12) and HSV thymidine kinase (TK), with tsK as
      the helper virus. In a 'suicide gene' strategy, ganciclovir (GCV) treatment after
      intratumoral inoculation of dvlacZ-tk/tsK, encoding E. coli lacZ instead of IL
      12, resulted in enhanced antitumor activity. Antitumor activity was also enhanced
      by local expression of IL-12 from dvIL12-tk/tsK. The combination of IL-12
      cytokine therapy with GCV treatment was the most efficacious approach, with
      significantly greater inhibition of tumor growth than IL-12 or TK + GCV alone.
      These results illustrate the power of combining different cancer therapy
      approaches; 'suicide gene' therapy, cytokine therapy, and HSV vector infection.
      HSV vectors are particularly well suited to this because they can accommodate the
      insertion of large and multiple gene sequences.

PMID- 11313809
TI  - Polymer-coated adenovirus permits efficient retargeting and evades neutralising
      antibodies.
AB  - Adenovirus is a widely used vector for cancer gene therapy because of its high
      infection efficiency and capacity for transgene expression in both dividing and
      nondividing cells. However, neutralisation of adenovirus by pre-existing
      antibodies can lead to inefficient delivery, and the wide tissue distribution of
      the coxsackie and adenovirus receptor (CAR, the primary receptor for adenovirus
      type 5) precludes target selectivity. These limitations have largely restricted
      therapeutic use of adenovirus to local or direct administration. A successful
      viral gene therapy vector would be protected from neutralising antibodies and
      exhibit a preferential tropism for target cells. We report here the development
      of a covalent coating and retargeting strategy using a multivalent hydrophilic
      polymer based on poly-[N-(2-hydroxypropyl)methacrylamide] (pHPMA). Incorporation
      of targeting ligands such as basic fibroblast growth factor and vascular
      endothelial growth factor on to the polymer-coated virus produces ligand
      mediated, CAR-independent binding and uptake into cells bearing appropriate
      receptors. Retargeted virus is resistant to antibody neutralisation and can
      infect receptor-positive target cells selectively in mixed culture, and also in
      xenografts in vivo. Multivalent polymeric modification of adenovirus is an
      effective way of changing its tropism and interaction with the immune system. As
      a non-genetic one-step process, the technology is simple, versatile and should
      yield vectors with an improved safety profile.

PMID- 11313810
TI  - Augmentation of myocardial transfection using TerplexDNA: a novel gene delivery
      system.
AB  - Gene therapy is a potential new strategy for the treatment of cardiovascular
      disease. The most efficacious method of gene delivery remains a key hurdle to
      effective gene therapy. We present the application of a novel, nonviral gene
      delivery system (TerplexDNA) to augment myocardial transfection. The hearts of
      New Zealand white rabbits were injected with reporter genes, luciferase cDNA or
      beta-galactosidase cDNA, either as naked plasmid DNA or plasmid DNA complexed
      with stearyl-poly(L-lysine)-low density lipoprotein (TerplexDNA). Three day left
      heart myocardial cell lysates produced 44571 +/- 8730 RLU (RLU = total light
      units/mg protein) for the TerplexDNA luciferase rabbits versus 1638 +/- 567 RLU
      for the naked luciferase rabbits (P = 0.002). Thirty days after injection,
      myocardial lysates produced 677 +/- 52 RLU for the TerplexDNA luciferase hearts
      versus 18 +/- 3 RLU for the naked luciferase hearts (P = 0.002). Histologic
      analysis of the hearts transfected with beta-galactosidase showed that TerplexDNA
      increased the area and depth of transfection compared with the naked plasmid DNA
      alone. The hearts of Sprague-Dawley rats were injected in a similar fashion and
      analyzed at 1, 3, 5, 10, 15, 25 and 30 days after injection. The naked luciferase
      injected hearts showed transient elevation of luciferase activity to day 5 but
      fell back to baseline levels after that time-point. The TerplexDNA luciferase
      injected hearts had significantly elevated luciferase activity to 30 days. The
      Terplex gene delivery system significantly augments myocardial transfection
      compared with a naked plasmid DNA system alone. The advantage in transfection
      efficiency appears to be related to the unique properties of the TerplexDNA
      carrier molecule. The TerplexDNA delivery system represents a novel means to
      augment transfection of the myocardium.

PMID- 11313811
TI  - Intravenous administration of an E1/E3-deleted adenoviral vector induces
      tolerance to factor IX in C57BL/6 mice.
AB  - Inbred immunocompetent C57BL/6 mice have been a favored strain to study transgene
      expression of human blood coagulation factor IX (hF.IX) from viral vectors
      because systemic expression of the secreted protein is not limited by antibody
      responses following intravenous (i.v.) injection of vector. For example, i.v.
      injection of an adenoviral (Ad) vector results in sustained expression of hF.IX
      in normal or hemophilic C57BL/6 mice, while anti-hF.IX antibodies rapidly emerge
      in other strains (Gene Therapy 4: 473; Blood 91: 784). To investigate these
      observations further, we injected naive C57BL/6 mice and C57BL/6 mice with pre
      existing anti-hF.IX with Ad-hF.IX vector via peripheral vein. All mice expressed
      hF.IX antigen without detectable anti-hF.IX, even when challenged with hF.IX in
      different immunogenic settings at later time points. Moreover, in mice with pre
      existing immunity, anti-hF.IX titers diminished to undetectable levels after i.v.
      administration of Ad-hF.IX. Lymphocytes from mice that had received Ad-hF.IX i.v.
      failed to proliferate when stimulated with hF.IX in vitro after the animals had
      been repeatedly challenged with hF.IX protein formulated in complete Freund's
      adjuvant. Thus, absence of anti-hF.IX in C57BL/6 mice after i.v. injection of Ad
      vector is not due to ignorance to the foreign transgene product. Similar
      experiments in other strains showed that immune tolerance to hF.IX does not
      correlate with the strain haplotype or expression of IL-10 cytokine. Given the
      well-documented immunogenicity of the first-generation adenoviral vector, data
      from C57BL/6 mice may therefore grossly underestimate immunological consequences
      in certain gene therapy protocols.

PMID- 11313812
TI  - Receptor-mediated gene delivery to human peripheral blood mononuclear cells using
      anti-CD3 antibody coupled to polyethylenimine.
AB  - Gene transfer to primary cells, especially to lymphoid cells, using a nonviral
      delivery system has been very challenging. In the present studies, we have used a
      cationic polymer, polyethylenimine (PEI) coupled to an anti-CD3 antibody for
      achieving receptor-mediated gene delivery to human peripheral blood mononuclear
      cells (PBMC). Naive, unstimulated PBMC did not express transfected genes, whereas
      the transgenes were expressed efficiently in PHA activated PBMC. Transiently
      expressed gene products were detected maximally at 24 and 48 h following
      transfection. Gene expression was detected until 96 h with a gradual diminution
      in the signal after 48 h. Receptor-mediated gene delivery was successfully used
      for freshly isolated, as well as previously frozen lymphocyte samples. The
      transfections performed using ligands other than anti-CD3 were not as efficient
      as anti-CD3-PEI. These results suggest that in addition to receptor-mediated
      endocytosis, signaling subsequent to engagement of the CD3 receptor with anti-CD3
      PEI appears to be important for the efficacy of anti-CD3-PEI mediated gene
      delivery.

PMID- 11313813
TI  - Replication and cytolysis of an E1B-attenuated adenovirus in drug-resistant
      ovarian tumour cells is associated with reduced apoptosis.
AB  - Therapeutic approaches which are effective in tumour cells resistant to
      conventional chemotherapy would be of value. An E1B 55 kDa-deleted adenovirus
      (ONYX-015) induces lysis in cells with mutant p53, although the specificity of
      these observations for different cell types is unclear. We have used a matched
      set of drug-resistant human ovarian tumour cell lines to examine the potential of
      ONYX-015 for preferential replication and lysis of drug-resistant ovarian tumour
      cells with documented alterations in p53 function. Marked preferential
      replication of ONYX-015 is observed after infection of mutant p53 transfectant
      and cisplatin-resistant derivatives, compared to the wild-type p53 expressing
      parental A2780 line. Infection causes increased cytopathic effects in vitro and
      inhibition of tumour growth in vivo of the drug-resistant derivatives, but not
      the parental line. In apparent contrast, increased apoptosis and reduced
      clonogenic survival is induced by ONYX-015 infection of the chemosensitive
      parental cell line. ONYX-015 induces increased pro-apoptotic BAX and reduced anti
      apoptotic BCLX(L) in parental cells, but not in the resistant derivative
      A2780/cp70. We propose that induction of apoptosis is one factor which prevents
      ONYX-015 spread and cytolysis after infection of chemosensitive cells, while it
      is the failure to engage apoptosis in drug-resistant cells that allows
      preferential viral replication, spread and cytolysis.

PMID- 11313814
TI  - Enhancement of suicidal DNA vaccine potency by linking Mycobacterium tuberculosis
      heat shock protein 70 to an antigen.
AB  - Naked DNA vaccines represent an attractive approach for generating antigen
      specific immunity because of their stability and simplicity of delivery. There
      are particular concerns with DNA vaccines however, such as potential integration
      into the host genome, cell transformation, and limited potency. The usage of DNA
      based alphaviral RNA replicons (suicidal DNA vectors) may alleviate the concerns
      of integration or transformation since suicidal DNA vectors eventually cause
      lysis of transfected cells. To improve further the potency of suicidal DNA
      vaccines, we evaluated the effect of linking Mycobacterium tuberculosis heat
      shock protein 70 (Hsp70) to human papillomavirus type 16 (HPV-16) E7 as a model
      antigen on antigen-specific immunity generated by a DNA-based Semliki Forest
      virus (SFV) RNA vector, pSCA1. Our results indicated that this suicidal DNA
      vaccine containing E7/Hsp70 fusion genes generated significantly higher E7
      specific T cell-mediated immune responses than vaccines containing the wild-type
      E7 gene in vaccinated mice. More importantly, this fusion converted a less
      effective vaccine into one with significant potency against established E7
      expressing metastatic tumors. The antitumor effect was predominantly CD8
      dependent. These results indicate that linkage of Hsp70 to the antigen may
      greatly enhance the potency of suicidal DNA vaccines.

PMID- 11313815
TI  - Efficient expression of foreign genes in human CD34(+) hematopoietic precursor
      cells using electroporation.
AB  - Introduction of foreign genes into human CD34(+) hematopoietic precursor cells
      offers a means to correct inborn errors or to protect human stem cells from
      chemotherapeutic damage. Electroporation is a non-chemical, nonviral, highly
      reproducible means to introduce foreign genes into mammalian cells that has been
      used primarily for rapidly dividing cells. CD34(+) cells isolated from mobilized
      peripheral blood of patients were cultured for 48 h in serum-free culture medium
      supplemented with Flt-3 ligand, stem cell factor and thrombopoietin. Cell cycle
      analysis showed an increase in % S-phase from 2% on day 0 to 28% on day 2 without
      significant loss of mean fluorescence intensity (MFI). Optimal electroporation
      conditions for CD34(+) cells were 550 V/cm, 38 ms, 30 microg DNA/500 microl at
      cell densities between 0.2 x 10(6) and 10 x 10(6) cells/ml resulting in transient
      EGFP gene expression in 21% (+/- 1%) of CD34(+) precursor cells, as determined by
      flow cytometry 48 h after electroporation. The more primitive cells were also
      found to be EGFP(+) as determined by subset analysis using Thy1, CD38, AC133 and
      c-kit conjugated monoclonal antibodies. Methylcellulose assays on electroporated
      CD34(+) cells yielded 20% (+/- 7%) EGFP(+) colonies (CFU-GM, BFU-E and CFU-mix)
      and 22% (+/- 5%) EGFP(+) long-term colony-initiating cells (LTC-IC). The reporter
      gene was found to be integrated into the LTC-IC genomic DNA as determined by
      inverse PCR and DNA sequencing. These results suggest that electroporation has
      the potential to effectively and stably deliver exogenous genes into human
      hematopoietic precursor cells.

PMID- 11313816
TI  - Targeted gene correction by small single-stranded oligonucleotides in mammalian
      cells.
AB  - We demonstrate that relatively short single-stranded oligodeoxynucleotides, 25-61
      bases homologous to the target sequence except for a single mismatch to the
      targeted base, are capable of correcting a single point mutation (G to A) in the
      mutant beta-galactosidase gene, in nuclear extracts, episome, and chromosome of
      mammalian cells, with correction rates of approximately 0.05%, 1% and 0.1%,
      respectively. Surprisingly, these short single-stranded oligonucleotides (ODN)
      showed a similar gene correction frequency to chimeric RNA-DNA oligonucleotide,
      measured using the same system. The in vitro gene correction induced by ODN in
      nuclear extracts was not dependent on the length or polarity of the
      oligonucleotide. In contrast, the episomal and chromosomal gene corrections were
      highly dependent on the ODN length and polarity. ODN with a homology of 45
      nucleotides showed the highest frequency and ODN with antisense orientation
      showed a 1000-fold higher frequency than sense orientation, indicating a possible
      influence of transcription on gene correction. Deoxyoligonucleotides showed a
      higher frequency of gene correction than ribo-oligonucleotides of the identical
      sequence. These results show that a relatively short ODN can make a sequence
      specific change in the target sequence in mammalian cells, at a similar frequency
      as the chimeric RNA-DNA oligonucleotide.

PMID- 11313817
TI  - Intramuscular electroporation delivery of IFN-alpha gene therapy for inhibition
      of tumor growth located at a distant site.
AB  - Although electroporation has been shown in recent years to be a powerful method
      for delivering genes to muscle, no gene therapy via electro-injection has been
      studied for the treatment of tumors. In an immunocompetent tumor-bearing murine
      model, we have found that delivery of a low dose of reporter gene DNA (10 microg)
      to muscle via electroporation under specific pulse conditions (two 25-ms pulses
      of 375 V/cm) increased the level of gene expression by two logs of magnitude.
      Moreover, administration of 10 microg of interferon (IFN)-alpha DNA plasmid using
      these parameters once a week for 3 weeks increased the survival time and reduced
      squamous cell carcinoma (SCC) growth at a distant site in the C3H/HeJ
      immunocompetent mouse. IFN-alpha gene therapy delivered to muscle using
      electroporation demonstrated statistically significant (P < 0.05) therapeutic
      efficacy for treating SCC located at a distant site, compared with interleukin
      (IL)-2 or endostatin gene, also delivered by electro-injection. The increased
      therapeutic efficacy was associated with a high level and extended duration of
      IFN-alpha expression in muscle and serum. We also discovered that the high level
      of IFN-alpha expression correlated with increased expression levels of the
      antiangiogenic genes IP-10 and Mig in local tumor tissue, which may have led to
      the reduction of blood vessels observed at the local tumor site. Delivery of
      increasing doses (10-100 microg) of IFN-alpha plasmid DNA by injection alone did
      not increase antitumor activity, whereas electroporation delivery of increasing
      doses (10-40 microg) of IFN-alpha plasmid DNA did increase the survival time. Our
      data clearly demonstrate the potential utility of electroporation for delivery of
      gene therapy to muscle for the treatment of residual or disseminated tumors.

PMID- 11313818
TI  - Inhibition of HIV-1 infection by down-regulation of the CXCR4 co-receptor using
      an intracellular single chain variable fragment against CXCR4.
AB  - CXCR4 is the major co-receptor used by X4 strains of human immunodeficiency virus
      type I (HIV-1). In HIV-1-infected patients, the appearance of X4 strains (T cell
      line-tropic) correlates with disease progression. Since its discovery, the CXCR4
      co-receptor has been a major target for different agents which block its
      function, such as stromal-derived factor 1alpha (SDF-1alpha) and the anti-CXCR4
      monoclonal antibody, 12G5. In the present studies, the 12G5 hybridoma was used to
      construct a single-chain variable antibody fragment (SFv). Murine leukemia virus
      (MLV) and simian virus 40 (SV(40)) were utilized as delivery vehicles for the
      anti-CXCR4 SFv. Intracellular expression of the anti-CXCR4 SFv led to down
      regulation of this critical co-receptor, as demonstrated by immunostaining. This
      effect significantly and specifically protected transduced cells from challenge
      with HIV-1, as measured by HIV-1 p24 antigen expression. Inhibition of HIV-1
      replication was specific for X4 HIV-1 strains as demonstrated by MAGI assays.
      HeLa-CD4/betagal-CCR5 cells expressing the anti-CXCR4 SFv showed significant
      inhibition of infectivity by the X4 HIV-1 strain NL4-3, but not with the R5 HIV-1
      strain Bal. Thus, this anti-HIV-1 molecular therapy has the potential to inhibit
      HIV-1 replication and virion spread. Targeting CXCR4 by intracellular
      immunization could be of additional benefit to certain HIV-1-infected patients on
      highly active antiretroviral therapy (HAART).

PMID- 11313819
TI  - Maturation of dendritic cells infected by recombinant adenovirus can be delayed
      without impact on transgene expression.
AB  - Adenovirus-mediated gene transfer to dendritic cells is highly efficient and
      often used, but the relationship among cell maturation, viral infection and
      expression of a transferred gene remains unclear. To study this relationship, we
      introduced a recombinant replication-defective adenovirus encoding the gene for
      green fluorescent protein to normal human immature myeloid dendritic cells. We
      induced maturation by the addition of TNF-alpha, IL-1beta, IL-6 and prostaglandin
      E2 to the medium and assessed cell maturity by the levels of the secreted p40
      subunit of IL-12 and of membrane-bound CD83. We quantified the efficiency of gene
      expression by GFP fluorescence and analyzed the data by a mixed-model analysis of
      variance; the model explained more than 97% of the effects. CD83 expression and
      p40 secretion depended solely on incubation time and maturation medium. The cells
      cultured in the absence of maturation medium remained immature and maintained the
      ability to respond to the later addition of the maturation irrespective of
      adenovirus infection and transferred gene expression. This expression was
      independent of cell maturation. In comparison with mature cells, the transferred
      gene was expressed in immature dendritic cells with a lag compatible with the
      less effective initial step (infection and/or gene transfer) in the absence of
      the maturation medium rather than less effective later GFP synthesis. Expression
      of CD83 and p40 were unaffected by adenovirus infection and transferred gene
      expression. Thus, immature dendritic cells infected with recombinant adenoviruses
      can be matured when desired after transferred gene expression.

PMID- 11313820
TI  - Adenovirus-mediated apo(a)-antisense-RNA expression efficiently inhibits apo(a)
      synthesis in vitro and in vivo.
AB  - Apo(a) is a very atherogenic plasma protein without apparent function, which is
      highly expressed in humans. The variation in plasma Lp(a) concentration among
      individuals is considerable. Approximately 10-15% of the white population exhibit
      plasma Lp(a) concentrations above the atherogenic cut-off value of approximately
      30 mg/dl. Since there is currently no safe way of treating those patients with
      drugs, we have tested the possibility of interfering with apo(a) biosynthesis by
      adenovirus-mediated expression of antisense apo(a) mRNA comprising the 5' UTR,
      the signal sequence and the first three kringles of native apo(a). Transduction
      of rat hepatoma McA RH 7777 cells which stably expressed apo(a) with 18 kringle
      IV (KIV) domains with apo(a)-antisense adenovirus (AS-Ad) at multiplicity of
      infection (MOI) of 30 reduced apo(a) synthesis to 23% as compared with control
      cells. As apo(a) is not synthesized in laboratory animals, we induced
      biosynthesis of the N-terminal fragments of apo(a) in mice by adenovirus-mediated
      gene transfer. Cotransduction of these mice with AS-Ad, which expressed up to
      eight times higher amounts of apo(a) than stable transgenic apo(a) mice, led to
      an almost complete disappearance of apo(a) from plasma. We conclude that the
      proposed AS-construct is very efficient in interfering with apo(a) biosynthesis
      in vivo. The strategy of inducing the synthesis of a nonexpressed protein
      followed by knocking it out by AS technology may also be applicable to other
      systems.

PMID- 11313821
TI  - Generation of high-titer retroviral vector-producing macrophages as vehicles for
      in vivo gene transfer.
AB  - The goal of this project was to develop a novel gene transfer system based on
      macrophages (Mphi) as shuttles of recombinant retroviral vectors carrying
      therapeutic or marker genes. The murine Mphi cell line WGL5 was used as a source
      of Mphi for this study. We generated retrovirus-producing Mphi by transducing the
      WGL5 cells with a replication-defective retroviral vector carrying the enhanced
      green fluorescent protein (EGFP) reporter gene and the Moloney murine leukemia
      virus (MoMLV) as helper virus. We demonstrated stable integration of the
      recombinant retrovirus in the Mphi genome, efficient recombinant retrovirus
      production, and EGFP gene delivery to different cell lines in vitro. To evaluate
      Mphi-mediated EGFP gene transfer in vivo, allogeneic mice were injected s.c. with
      the retrovirus-producing WGL5 Mphi, that gave rise to solid tumor masses at the
      injection site, highly infiltrated with host leukocytes. We observed EGFP
      fluorescence in tumor-infiltrating CD4(+) and CD8(+) host T lymphocytes,
      providing direct evidence of the ability of engineered Mphi to mediate EGFP gene
      delivery to host cells in vivo. Moreover, we showed that retrovirus-producing
      Mphi could home to different organs in vivo following i.v. injection into mice.
      These data demonstrate that Mphi can be engineered as cellular vehicles for
      recombinant retroviruses carrying heterologous genes and suggest potential
      applications of this novel vector system for gene therapy.

PMID- 11313822
TI  - Pharmacologically regulated gene expression in the retina following transduction
      with viral vectors.
AB  - The availability of inducible expression systems makes regulatable control of
      therapeutic proteins an attainable goal in gene therapy. We delivered
      tetracycline-inducible transgenes to the subretinal space using recombinant
      adenoviruses. Upon administration of doxycycline, we demonstrated reversible
      expression of green fluorescent protein in the retinal pigment epithelium as well
      as modulation of human growth hormone produced in the retina and secreted in the
      blood stream. This mode of delivery and regulation offers a unique way to
      evaluate gene function in the eye and represents a novel method for introducing
      therapeutic proteins into the retina.

PMID- 11313823
TI  - Insertion of the DNA for the 163-171 peptide of IL1beta enables a DNA vaccine
      encoding p185(neu) to inhibit mammary carcinogenesis in Her-2/neu transgenic
      BALB/c mice.
AB  - An assessment was made of the effectiveness of DNA vaccination in prevention of
      the mammary adenocarcinomas of BALB/c female mice transgenic for the activated
      rat Her-2/neu oncogene. Atypical hyperplasia is evident in their mammary glands
      when they are 6 weeks old and in situ carcinoma by the 13th week. Palpable
      invasive carcinomas appear around the 17th week and are always evident in all 10
      glands by the 33rd week. Intramuscular vaccinations with 100 microg plasmid DNA
      encoding the extracellular domain of the Her-2/neu p185 (ECD) performed at the
      6th, 12th, 18th and 24th week provided no significant protection, whereas those
      ECD plasmids in which the DNA coding for the immunomodulatory 163-171 (VQGEESNDK)
      nonapeptide of human IL1beta (ECD-IL1betap) had been inserted both delayed
      carcinogenesis and reduced tumor multiplicity. This reduction was associated with
      a marked immune-inflammatory reaction and a conspicuous leukocyte infiltrate
      located in the stroma surrounding the hyperplastic mammary ductul-alveolar
      structures. It was also directly correlated with a high anti-p185(neu) antibody
      production and an immunoglobulin switch to IgG2a and IgA. No anti-p185(neu)
      cytotoxic response was found. No significant protection was obtained when the DNA
      coding for the non-active peptide 189-197 of IL1beta was inserted.

PMID- 11313824
TI  - Enhanced cationic liposome-mediated transfection using the DNA-binding peptide mu
      (mu) from the adenovirus core.
AB  - Promising advances in nonviral gene transfer have been made as a result of the
      production of cationic liposomes formulated with synthetic cationic lipids
      (cytofectins) that are able to transfect cells. However few cationic liposome
      systems have been examined for their ability to transfect CNS cells. Building
      upon our earlier use of cationic liposomes formulated from 3beta-[N-(N',N'
      dimethylaminoethane)carbamoyl] cholesterol (DC-Chol) and dioleoyl-L-alpha
      phosphatidyl-ethanolamine (DOPE), we describe studies using two cationic viral
      peptides, mu (mu) and Vp1, as potential enhancers for cationic liposome-mediated
      transfection. Mu is derived from the condensed core of the adenovirus and was
      selected to be a powerful nucleic acid charge neutralising and condensing agent.
      Vp1 derives from the polyomavirus and harbours a classical nuclear localisation
      signal (NLS). Vp1 proved disappointing but lipopolyplex mixtures formulated from
      pCMVbeta plasmid, mu peptide and DC-Chol/DOPE cationic liposomes were able to
      transfect an undifferentiated neuronal ND7 cell line with beta-galactosidase
      reporter gene five-fold more effectively than lipoplex mixtures prepared from
      pCMVbeta plasmid and DC-Chol/DOPE cationic liposomes. Mu was found to give an
      identical enhancement to cationic liposome-mediated transfection of ND7 cells as
      poly-L-lysine (pLL) or protamine sulfate (PA). The enhancing effects of mu were
      found to be even greater (six- to 10-fold) when differentiated ND7 cells were
      transfected with mu-containing lipopolyplex mixtures. Differentiated ND7 cells
      represent a simple ex vivo-like post-mitotic CNS cell system. Successful
      transfection of these cells bodes well for transfection of primary neurons and
      CNS cells in vivo. These findings have implications for experimental and
      therapeutic uses of cationic liposome-mediated delivery of nucleic acids to CNS
      cells.

PMID- 11313825
TI  - Long-term production of erythropoietin after electroporation-mediated transfer of
      plasmid DNA into the muscles of normal and uremic rats.
AB  - The anemia associated with chronic renal failure is one of the best target
      diseases for erythropoietin (Epo) gene transfer. We previously reported a short
      term (1 month) study of continuous rat Epo delivery by muscle-targeted gene
      transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo
      electroporation in normal rats. Here, we performed a long-term pharmacokinetic
      study of continuous Epo delivery by this method in normal rats and uremic five
      sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient
      erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and
      persisted for at least 11 weeks. Repeated administration of the plasmid DNA
      effectively produced erythropoiesis. Similar erythropoiesis was observed in the
      uremic rats, and persisted for more than 15 weeks. Both normal and uremic rats
      showed a significant decrease in platelet count. Moreover, the uremic rats showed
      Epo-induced hypertension, which is the major side-effect of recombinant human
      Epo. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in
      vivo electroporation is a useful procedure for the long-term continuous delivery
      of Epo in both normal and uremic rats.

PMID- 11313826
TI  - Death receptor-independent cytochrome c release and caspase activation mediate
      thymidine kinase plus ganciclovir-mediated cytotoxicity in LN-18 and LN-229 human
      malignant glioma cells.
AB  - Suicide gene therapy using viral transfer of herpes simplex virus type I (HSV-1)
      thymidine kinase (TK) and subsequent ganciclovir (GCV) chemotherapy was the first
      approach used in clinical trials of somatic gene therapy for glioblastoma. The
      molecular pathways mediating TK/GCV-induced cell death remain to be elucidated.
      Here, we report that adenoviral (Ad)-TK/GCV-induced death is p53-independent and
      does not involve altered CD95 or CD95L expression. Ectopic expression of the
      preferential caspase 8 inhibitor, crm-A, inhibits Ad-CD95L-induced cell death but
      has no effect on TK/GCV cytotoxicity. LN-18 glioma cells selected for resistance
      to death receptor-mediated cell death do not acquire cross-resistance to TK/GCV.
      TK/GCV triggers mitochondrial cytochrome c release and activation of caspases 3,
      7, 8 and 9 in a death receptor-independent manner. These events are associated
      with the loss of BCL-X(L). Forced expression of a BCL-X(L) transgene, or co
      exposure to a pseudosubstrate caspase inhibitor, zVAD-fmk, inhibit TK/GCV
      cytotoxicity. Double-transfected cell lines expressing crm-A and enhanced green
      fluorescent protein (eGFP) show that the bystander effect in vitro is also death
      receptor- and caspase 8-independent. TK/GCV therapy does not kill glioma cells in
      synergy with cancer chemotherapy drugs, including lomustine, temozolomide and
      topotecan. In contrast, there is strong synergy of TK/GCV and CD95L. Thus, TK/GCV
      induced cell death involves a mitochondria-dependent loop of caspase acvtivation
      that can be synergistically enhanced by death receptor agonists such as CD95L.
      TK/GCV-mediated sensitization of glioma cells to CD95L expressed on immune
      effector cells or parenchymal brain cells might account for the immune system's
      and bystander effects of TK/GCV therapy observed in rodent glioma models in vivo.

PMID- 11313827
TI  - Influence of multiplicity of infection and protein stability on retroviral vector
      mediated gene expression in hematopoietic cells.
AB  - Using retroviral vectors encoding enhanced green fluorescent protein (EGFP), we
      addressed to what extent expression of retroviral transgenes in hematopoietic
      cells depends on the multiplicity of infection (MOI) and on the half-life of the
      encoded protein. We show that an elevation of the MOI not only elevates the
      frequency of transduced cells, but also increases transgene expression levels and
      reduces interanimal variability in vivo (hematopoietic cells of C57BL/6J mice
      analyzed 13 weeks after transplantation). This suggests that the MOI has to be
      carefully controlled and should be adapted as desired for clinical studies when
      evaluating vector performance in preclinical models. The impact of protein
      stability is demonstrated by comparing vectors expressing EGFP or a destabilized
      variant with a C-terminal PEST-sequence, d2EGFP. The loss of expression with
      d2EGFP was more pronounced in terminally differentiated cells of the peripheral
      blood (>30 fold) than in progenitor cells (five- to 10-fold), indicating a
      stronger transcription of the retroviral promoter in progenitor cells and a
      predominant role of protein inheritance over de novo synthesis of transgenic
      protein in mature blood cells. This analysis reveals an important and
      differentiation-dependent contribution of protein half-life to the expression of
      retroviral vectors in hematopoietic cells, establishes d2EGFP as a more accurate
      reporter for determination of vector transcription, and also suggests that
      preclinical data obtained under conditions of high transduction rates or with
      vectors expressing stable reporter proteins require careful interpretation.

PMID- 11313828
TI  - MHC class II presentation of endogenously expressed antigens by transfected
      dendritic cells.
AB  - Dendritic cells (DC) present immunogenic epitopes of antigens in the context of
      MHC class I and class II molecules in association with costimulatory molecules,
      and efficiently activate both cytotoxic T cells and T helper cells. Gene modified
      DC expressing antigen encoding cDNA represent a particularly attractive approach
      for the immunotherapy of disease. We previously described a gene delivery system
      for DC based on receptor-mediated endocytosis of ligand/polyethylenimine (PEI)
      DNA transfer complexes that target cell surface receptors which are abundantly
      expressed on DC. Employing this gene delivery system, DC were generated that
      express chicken ovalbumin (OVA) cDNA as a model antigen and introduce antigen
      into the MHC class I presentation pathway. We demonstrate here that modification
      of OVA cDNA as transferrin receptor (TfR) or invariant chain (Ii) fusions
      effectively generate MHC class II specific immune responses in addition to MHC
      class I responses. TfR-OVA contains the membrane anchoring region of transferrin
      receptor and represents a membrane-bound form of OVA for access to the MHC class
      II compartment. Ii-OVA fusions directly target the MHC class II processing
      pathway. Thus, modification of antigen encoding cDNA represents a convenient and
      effective means to direct antigens to MHC class II presentation and thus to
      generate T cell help.

PMID- 11313829
TI  - Muscle-specific enhancement of gene expression by incorporation of SV40 enhancer
      in the expression plasmid.
AB  - Skeletal muscle is established as an ideal tissue for gene delivery to treat
      systemic diseases. However, the relatively low levels of gene expression obtained
      from using naturally occurring promoters, including the strong cytomegalovirus
      (CMV) enhancer/promoter (E/P), have limited the use of muscle as a target tissue.
      The relatively weak simian virus 40 (SV40) enhancer is known to have dual
      functions promoting localization of DNA to the nucleus and activating
      transcription. An SV40 enhancer incorporated either at the 5' end of CMV E/P or
      the 3' end of the polyadenylation site gave as much as a 20-fold increase in the
      level of exogenous gene expression in muscle in vivo, compared with expression
      observed with CMV E/P alone. The minimum requirement for this enhancement is a
      single copy of a 72-bp element of the SV40 enhancer, in combination with either
      the CMV E/P or skeletal actin (SkA) promoter. Enhancement of gene expression in
      muscle by this SV40 enhancer was also observed by using the powerful
      electroporation delivery. However, the SV40 enhancer does not increase the level
      of CMV E/P driven reporter gene expression in dividing tumor cells in vivo and in
      the dividing myoblast cell C2C12 in vitro. The data suggest that including this
      enhancer in the plasmid will enhance the level of gene production for muscle
      based gene therapy.

PMID- 11313831
TI  - On-demand IC351 (Cialis) enhances erectile function in patients with erectile
      dysfunction.
AB  - IC351 (Cialis) is a selective inhibitor of PDE5. The efficacy and safety of on
      demand dosing of IC351 in men with erectile dysfunction was assessed in a
      multicenter, double-blind, placebo-controlled study. One hundred seventy-nine men
      (mean age: 56 y) were randomized to receive placebo or IC351 at doses of 2, 5, 10
      or 25 mg, taken on demand over a 3-week period. The primary endpoints were change
      from baseline in responses to Questions 3 (Q3) and 4 (Q4) of the International
      Index of Erectile Function (IIEF). IC351 significantly improved IIEF Q3 scores at
      all doses vs placebo (P < or =0.003). IC351 also significantly improved IIEF Q4
      scores in all but the 2 mg group (P < or =0.0003). No significant changes in
      laboratory values, ECGs, or blood pressure were observed. The most common adverse
      events were headache and dyspepsia. The conclusion of this study was that on
      demand IC351 at doses up to 25 mg was well tolerated and significantly improved
      erectile function.

PMID- 11313832
TI  - Are normal hemodynamic responses invariably associated with normal penile
      rigidity and potency?
AB  - The existence and importance of patients with low penile buckling pressure and
      normal penile hemodynamic status have been recently recognized. We assessed the
      ratio of inadequate erection for vaginal penetration (low buckling pressure) in
      patients with normal penile vascular system proved with penile Doppler
      ultrasonography. A total of 101 patients with normal penile vascular status were
      retrospectively scrutinized dependent on penile axial rigidity (buckling
      pressure). Ninety patients had sufficient penile axial rigidity (> or = 550 g)
      whereas in the remaining 11 patients (11%) inadequate penile buckling pressure
      for vaginal penetration (< 550 g) was determined. Penile geometric and mechanical
      properties should not be overlooked during the evaluation of penile vascular
      system lest the patient be incorrectly diagnosed as having psychogenic impotence.

PMID- 11313835
TI  - Stability evaluation of a prostaglandin E1 saline solution packed in insulin
      syringes.
AB  - This article describes the preparation and stability of a sterile prostaglandin
      E1 solution. The solution is packed in insulin syringes as single dose injections
      for the treatment of erectile disfunction. The stability of this preparation is
      24 weeks when stored at 5 degrees C.

PMID- 11313836
TI  - Peyronie's disease in men under age 40: characteristics and outcome.
AB  - Peyronie's disease is most commonly seen in the fifth decade of life. However, a
      wide range of age (20-83 y) is reported. During a 6-year period, men with
      Peyronie's disease presenting under the age of 40 were reviewed retrospectively
      and followed-up. The prevalence of Peyronie's patients presenting under age 40
      was 8.2%. Their mean age was 32.47 +/- 5.37 (range: 23-39) y and 78.9% of them
      presented during the acute phase of the disease. Pain on erection was a part of
      presenting symptom complex in 52.6% and the majority (84%) had a degree of penile
      curvature < 60 degrees. Erectile dysfunction (ED) was present in 21% of patients,
      who responded well to intracavernous injection test. After a minimal 2-year
      follow-up, improvement in penile deformity was observed in 36.8%, and 42.1% had
      stable disease while 21% experienced deterioration of the penile curvature. The
      onset of Peyronie's disease is clinically more noisy and acute in patients
      presenting under age 40 and this forces the physicians to treat them more
      vigorously.

PMID- 11313837
TI  - Effects of the specific phosphodiesterase inhibitors on alloxan-induced diabetic
      rabbit cavernous tissue in vitro.
AB  - An experimental study was done to examine a potential role of phosphodiesterase
      (PDE) inhibitors in the treatment of diabetic erectile dysfunction. Relaxant
      effect of specific PDE inhibitors were measured in strips of corpus cavernosum
      smooth muscle taken from control and diabetic groups. Diabetes mellitus was
      induced in New Zealand white rabbits using alloxan. Penises excised from diabetic
      rabbits 8 weeks after the induction of diabetes mellitus. In the organ bath
      strips from control and diabetic rabbit corpus cavernosum were precontracted and
      increasing doses of several PDE inhibitors were added. In the precontracted
      rabbit cavernous tissue, sulmazole and zaprinast specific PDE V inhibitors were
      equally potent and efficacious in vitro but amrinone, a specific PDE III
      inhibitor, exhibits low relaxant effects. All PDE inhibitors tested showed a
      similar relaxation effect on corpus cavernosum smooth muscle from control and 8
      week diabetic rabbits. The present study provides the possibility of using
      selective PDE III and V inhibitors in the treatment of diabetic impotence.

PMID- 11313838
TI  - Sex, drugs, and hypertension: a methodological approach for studying a sensitive
      subject.
AB  - Sexual dysfunction is a recognized side effect of hypertension and
      antihypertensive medications in men, but is not established as a side effect in
      women, due to the lack of established methodology. An ambulatory medical record
      based, case-control study was designed to study sexual function in treated and
      untreated hypertensive women and healthy controls. The research was performed in
      a teaching hospital with satellite clinics in upstate New York. There were 3312
      medical records reviewed, 640 premenopausal Caucasian women in heterosexual
      relationships subjects were eligible for participatic diagnosis of mild
      hypertension (BP > or =140/90 mmHg and < 160/100 mmHg) for cases; no other
      significant medical history. A total of 241 women agreed to participate, 224
      (35%) completed both a self-administered questionnaire and a telephone interview
      (112 healthy, 112 hypertensive). There was an initial 74% response rate among
      those eligible to participate, with 35% completing the entire study. Age and
      average blood pressure were not significant between 224 participants and 416
      nonparticipants by 2-tailed t-test analysis. Seven composite variables were
      formed from a 47-item sexual response questionnaire. Initial unadjusted chi2
      results reported women with hypertension had more difficulty than did healthy
      controls achieving lubrication and orgasm. Seven questions, each with the highest
      correlation to its respective composite variable (by Spearman's correlation),
      formed an abbreviated questionnaire. Quality of female sexual function was
      quantified in an ambulatory outpatient setting. A method was described to address
      hypertension, pharmacotherapy, and sexual functioning by employing self
      administered questionnaires and telephone interviews. Initial analysis suggested
      that hypertensive women may have an impaired physiological sexual response. The
      abbreviated questionnaire generated from questions with the highest correlation
      to their respective composite variables may be useful in further evaluating this
      issue.

PMID- 11313839
TI  - Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in
      premature ejaculation.
AB  - The objective was to compare the efficacy and safety of the as needed use of
      clomipramine, sertraline, paroxetine, sildenafil and the pause-squeeze technique
      in treatment of primary premature ejaculation. A prospective double blind
      randomized crossover study involving 31 patients was performed. Treatment phases
      comprised five 4-week consecutive treatment periods, each separated by a two-week
      washout period. Patients were randomly assigned to receive each of the 4 drugs
      and use pause-squeeze on an as needed basis. Drugs were administered 3 to 5 hours
      before anticipated coitus. Anxiety score and ejaculation latency time were
      measured before treatment, after each treatment, and during washout periods.
      Sexual satisfaction score was measured after each treatment. The median
      ejaculation latency time was significantly increased from the pretreatment median
      of 1 minute to 4 minutes, 3 minutes, 4 minutes, 15 minutes and 3 minutes during
      treatment with clomipramine, sertraline, paroxetine, sildenafil and pause-squeeze
      technique, respectively (all P 0.0001). Sildenafil was superior to other
      modalities in terms of ejaculation latency and satisfaction (P = 0.0001). The
      three antidepressants were comparable to each other in terms of efficacy (P >
      0.05). Paroxetine was superior to the pause-squeeze technique in terms of
      efficacy (P < 0.05). In conclusion, sildenafil appears to be superior to other
      modalities and a valid alternative in treatment of premature ejaculation. The 3
      antidepressants were equivalent to each other in terms of efficacy and safety.
      Paroxetine was superior to pause-squeeze technique in terms of efficacy.

PMID- 11313840
TI  - Idiopathic corpus cavernosal haemorrhage.

PMID- 11313841
TI  - Penile resurfacing for extensive genital warts.
AB  - Complete surgical excision followed by reconstruction, of diseased penile skin
      may result in sexual dysfunction due to tethering of the underlying Buck's fascia
      by the graft. We describe penile resurfacing for extensive condyloma accuminata,
      a novel technique that circumvents this complication without compromising
      clearance of this particular lesion.

PMID- 11313842
TI  - The etiology of premature ejaculation starting from a bihormonal model of normal
      sexual stimulation.

PMID- 11313844
TI  - 9th world meeting on impotence research. Incorporating the 12 symposium on corpus
      cavernosum revascularization. 26-30 November 2000, Perth, Australia. Abstracts.

PMID- 11313843
TI  - Penile fracture repair. Assessment of early results and complications using color
      Doppler ultrasound.

PMID- 11313858
TI  - Bloom helicase is involved in DNA surveillance in early S phase in vertebrate
      cells.
AB  - Bloom syndrome (BS) is a recessive human genetic disorder characterized by short
      stature, immunodeficiency and an elevated risk of malignancy. The gene mutated in
      BS, BLM, encodes a RecQ-type DNA helicase. BS cells have mutator phenotypes such
      as hyper-recombination, chromosome instability and an increased frequency of
      sister chromatid exchange (SCE). To define the primary role of BLM, we generated
      BLM(-/-) mutants of the chicken B-cell line DT40. In addition to characteristics
      of BLM(-/-) cells reported previously by the other group, they are hypersensitive
      to genotoxic agents such as etoposide, bleomycin and 4-nitroquinoline-1-oxide and
      irradiation with the short wave length of UV (UVC) light, whereas they exhibit
      normal sensitivity to X-ray irradiation and hydroxyurea. UVC irradiation to BLM(
      /-) cells during G(1) to early S phase caused chromosomal instability such as
      chromatid breaks and chromosomal quadriradials, leading to eventual cell death.
      These results suggest that BLM is involved in surveillance of base abnormalities
      in genomic DNA that may be encountered by replication forks in early S phase.
      Such surveillance would maintain genomic stability in vertebrate cells, resulting
      in the prevention of cellular tumorigenesis.

PMID- 11313859
TI  - Alterations in the focal adhesion kinase/Src signal transduction pathway
      correlate with increased migratory capacity of prostate carcinoma cells.
AB  - Focal adhesion kinase (FAK) has been implicated in the regulation of cell
      migration. In addition, FAK expression is increased in a number of highly
      metastatic tumor cell lines. Therefore, we investigated the role of FAK in
      regulating migration of prostate carcinoma cell lines with increasing metastatic
      potential. We show that highly tumorigenic PC3 and DU145 cells exhibit intrinsic
      migratory capacity, while poorly tumorigenic LNCaP cells require a stimulus to
      migrate. Increased metastatic potential of PC3 and DU145 cells correlates with
      increased FAK expression, overall tyrosine phosphorylation and activity, as
      measured by autophosphorylation of tyrosine 397. However, in PC3 and DU145 cells,
      FAK autophosphorylation is adhesion dependent whereas a second site of tyrosine
      phosphorylation, tyrosine 861, a Src specific site, is uncoupled from adhesion
      dependent signaling events. Finally, inhibiting the FAK/Src signal transduction
      pathway by over expressing FRNK (Focal adhesion kinase-Related Non-Kinase), an
      inhibitor of FAK activation, or treatment with PP2, a Src family kinase
      inhibitor, significantly inhibited migration of prostate carcinoma cell lines,
      demonstrating that tumor cell migration continues to be dependent on signals
      emanating from this pathway.

PMID- 11313860
TI  - Expression of Mad1 in T cells leads to reduced thymic cellularity and impaired
      mitogen-induced proliferation.
AB  - To investigate Mad1 function in vivo, transgenic mice were generated that express
      a Mad1 transgene in T lineage cells under the control of the proximal lck
      promoter. Thymus size in lck-Mad1 transgenic mice is drastically reduced although
      representation of the various thymocyte sub populations appears normal. To
      investigate more closely any effects of Mad1 expression on thymocytes, we
      examined thymic selection using MHC class I-restricted H-Y-TCR transgenic mice.
      Mad1 expression in vivo reduces the efficiency of positive selection.
      Furthermore, thymocytes and splenic T cells from lck-Mad1 transgenic mice display
      a profound proliferative defect in response to activation with either
      PMA/Ionomycin or immobilized anti-CD3/CD28 antibody. This proliferative defect is
      not reversed by addition of exogenous IL-2 and is p53-independent. The growth
      inhibition caused by Mad1 is overcome by expression of active c-Myc.

PMID- 11313861
TI  - N-terminal domain of BARF1 gene encoded by Epstein-Barr virus is essential for
      malignant transformation of rodent fibroblasts and activation of BCL-2.
AB  - The BARF1 gene encoded by the Epstein-Barr virus induces morphological changes,
      loss of contact inhibition and anchorage independence in established rodent
      Balb/c3T3 fibroblast. BARF1 gene was also capable of inducing malignant
      transformation in a human Louckes B cell line. Our recent study showed that BARF1
      gene had an ability to immortalize primary epithelial cells. However we do not
      know which region(s) of BARF1 protein is(are) responsible for inducing malignant
      transformation in established rodent cells. Using the deletion mutants, we now
      localized a malignant transforming region in N-terminal of BARF1 protein. The
      mutants lacking this region were unable to transform the cells in malignant
      state. Furthermore, we demonstrated that only the mutants containing this region
      rendered the cells resistant to apoptosis induced by serum deprivation.
      Surprisingly, the BARF1 gene was capable of activating anti-apoptotic Bcl-2
      expression and this activation was due to the N-terminal transforming region.
      These data suggest that the cooperation of BARF1 with Bcl-2 is essential for the
      induction of malignant transformation.

PMID- 11313862
TI  - cAMP signaling selectively influences Ras effectors pathways.
AB  - Thyrotropin (TSH) stimulates survival and growth of thyroid cells via a seven
      transmembrane G protein-coupled receptor. TSH elevates the intracellular cyclic
      AMP (cAMP) levels activating protein kinase A (PKA). Recent evidence indicates
      that p21 Ras is required for TSH-induced mitogenesis, but the molecular
      mechanism(s) is not known. Here we report that Ras p21 activity is necessary for
      the Go- G1 transition in TSH induced cycle and that the downstream effector of
      Ras upon TSH signaling is p85-p110 PI3K. We show that PI3K inhibitors block TSH
      induced DNA synthesis, cAMP-PKA stimulate the formation of the complex PI3K-p21
      Ras and reduce the complex Ras-Raf1 in thyroid and other cells types. Moreover,
      PKA phosphorylates immunoprecipitated p85 and PKA phosphorylation of cell
      extracts significantly stimulates the formation of the complex PI3K-Ras. We
      suggest that PKA phosphorylates p85 and stabilizes the complex p110-p85,
      enhancing the interaction PI3K and p21 Ras. Simultaneously, cAMP inhibits Raf-1
      ERK signaling by decreasing Raf1 availability to Ras. Under these circumstances
      PI3K signaling is favored. These results indicate that PI3K is an important
      mediator of Ras effects in cAMP-induced proliferation and illustrates how cAMP
      can selectively influence Ras effector pathways.

PMID- 11313863
TI  - Staurosporine and conventional anticancer drugs induce overlapping, yet distinct
      pathways of apoptosis and caspase activation.
AB  - Apoptosis can be induced by various stimuli including DNA-damaging anticancer
      drugs and the protein kinase inhibitor staurosporine. It is generally believed
      that the molecular events during execution of apoptosis are shared, as both
      anticancer drugs and staurosporine derivatives induce mitochondrial damage,
      cytochrome c release and the activation of the caspase-9 proteolytic cascade. In
      the present study we show that overexpression of a dominant-negative caspase-9
      mutant abolished the activation of endogenous caspase-9, caspase-3 and the
      cleavage of the caspase substrate Bid in response to anticancer drug treatment.
      Surprisingly, however, only marginal effects were observed during staurosporine
      induced apoptosis. Furthermore, we describe a Jurkat T-cell clone that is
      completely resistant towards different anticancer drugs, but remains sensitive
      towards staurosporine-induced apoptosis. In these cells only staurosporine, but
      neither anti-CD95 nor anticancer drugs were able to trigger caspase activity and
      the cleavage of caspase substrates. Our results therefore suggest that the
      mechanism of staurosporine-induced apoptosis is more complex and at least
      partially differs from anticancer drug-induced caspase activation. These distinct
      features of staurosporine may allow to bypass chemoresistance of tumor cells and
      may encourage further clinical trials for the use of staurosporine derivatives in
      antitumor therapy.

PMID- 11313864
TI  - Caspase-dependent cleavage of the hematopoietic specific adaptor protein Gads
      alters signalling from the T cell receptor.
AB  - Gads is a SH2 and SH3 domain-containing, hematopoietic-specific adaptor protein
      that functions in signalling from the T cell receptor. Gads acts by linking SLP
      76, bound by the carboxy-terminal Gads SH3 domain, to tyrosine phosphorylated LAT
      which contains binding sites for the Gads SH2 domain. Gads is distinguished from
      Grb2 and the closely related Grap protein by the presence of a 120 amino acid
      unique region between the SH2 domain and the carboxy terminal SH3 domain. Here we
      demonstrate that the unique region of Gads contains a capase cleavage site.
      Induction of apoptosis in lymphocytes results in detectable Gads cleavage by 60
      min. Gads cleavage is blocked in vivo by treating cells with a caspase 3
      inhibitor. A putative caspase 3 cleavage site was identified within the unique
      region and mutation of this site prevented Gads cleavage in vitro, and in vivo.
      The Gads cleavage products retained the predicted binding specificity for SLP-76
      and LAT. Expression of the Gads cleavage products in Jurkat T cells inhibited
      NFAT activation following TCR cross linking. These findings indicate that
      cleavage of Gads in vivo could function to alter signalling downstream of the T
      cell receptor by disrupting cross talk between SLP-76 and LAT.

PMID- 11313865
TI  - p53 protein accumulation in addition to the transactivation activity is required
      for p53-dependent cell cycle arrest after treatment of cells with camptothecin.
AB  - In this study we characterize the connections between p53-dependent G1 cell cycle
      arrest, transcriptional activation of the protein and the increase of its
      intracellular steady-state concentration. Several cell lines expressing wild-type
      p53 protein were treated with increasing concentrations of DNA-damaging drug
      camptothecin. Lower doses of the drug caused transcriptional activation of p53,
      but no accumulation of the protein was detected. Only after a certain threshold
      dose of camptothecin does the amount of the protein rapidly increase and reach
      its plateau levels. The threshold dose was different for different cell lines,
      but the general non-linear profile was similar. Increase of p53 level was
      accompanied by additional transcriptional activation of some p53 target genes
      (i.e. waf1), but not the others (mdm2). We demonstrate here that transcriptional
      activation of p53 after the treatment of camptothecin is not sufficient to cause
      p53-dependent G1 cell cycle arrest. The latter is observable only after the
      increase of steady-state level of p53. Low drug concentrations, although
      accompanied by transcriptional activation of p53, do not cause either p53 protein
      accumulation nor cell cycle arrest at G1. We propose a model for p53 acting as a
      part of cellular sensor system detecting the severity of DNA damage.

PMID- 11313866
TI  - Upregulation of p21(WAF1/CIP1) leads to morphologic changes and esterase activity
      in TPA-mediated differentiation of human prostate cancer cell line TSU-Pr1.
AB  - We reported previously that human prostate cancer cell line TSU-Pr1 can
      differentiate into microglia-like cells by 12-O-tetra-decanoylphorbol-13-acetate
      (TPA) treatment. In this study, we identified a signal transduction pathway
      involved in TPA-induced TSU-Pr1 cell differentiation and investigated the
      mechanism of growth arrest that accompanies this differentiation. TPA-induced
      differentiation and growth arrest of TSU-Pr1 cells were inhibited by treatment
      with Protein kinase C (PKC) inhibitor GF109203X and mitogen-activated protein
      (MAP) kinase inhibitor PD98059. Treatment of TSU-Pr1 cells with TPA for 15 min or
      longer resulted in translocation of PKCalpha, PKCgamma, and PKCepsilon from
      cytosolic to membrane fraction. Our results suggest that TPA-induced TSU-Pr1 cell
      differentiation is associated with activation of MAP kinase and PKCalpha,
      PKCgamma, and PKCepsilon. The mechanism of growth arrest in TSU-Pr1 cells that
      underwent TPA-induced differentiation were examined for factors in the signaling
      pathway downstream of MAP kinase that control the cell cycle. Upregulation of
      p21(WAF1/CIP1) cyclin-dependent kinase inhibitor protein was observed in a manner
      dependent on PKC or MAP kinase. Moreover, adenovirus-mediated overexpression of
      recombinant p21(WAF1/CIP1) in TSU-Pr1 cells result in growth arrest,
      morphological change to microglia-like cells, and increased alpha-naphthyl
      acetate esterase activity, all of which are associated with cellular
      differentiation. Thus, our results indicate that p21(WAF1/CIP1) mediates TPA
      induced growth arrest and differentiation of TSU-Pr1 cells.

PMID- 11313867
TI  - A novel mutation within the extracellular domain of TrkA causes constitutive
      receptor activation.
AB  - The TrkA NGF receptor extracellular region contains three leucine repeats flanked
      by cysteine clusters and two immunoglobulin-like domains that are required for
      specific ligand binding. Deletion of the immunoglobulin-like domains abolishes
      NGF binding and causes ligand independent activation of the receptor. Here we
      report a specific mutation that increases the binding affinity of the TrkA
      receptor for NGF. A change of proline 203 to alanine (P203A) in the linker region
      between the leucine repeats and the first Ig-like domain increased NGF binding by
      decreasing the ligand rate of dissociation. This mutated receptor was
      appropriately expressed on the cell surface and promoted ligand-independent
      neurite outgrowth in PC12nnr5 cells. The mutant receptor was capable of
      spontaneous dimerization and was constitutively phosphorylated in the absence of
      ligand. Moreover, expression of TrkA-P203A receptor in fibroblasts induced DNA
      synthesis and transformation and generated tumours in nude mice. These data
      suggest that domains outside of the immunoglobulin-like structure contribute to
      ligand binding and constitutive activation of Trk receptors.

PMID- 11313868
TI  - Sequence-specific enhancer binding protein is responsible for the differential
      expression of ERT/ESX/ELF-3/ESE-1/jen gene in human gastric cancer cell lines:
      Implication for the loss of TGF-beta type II receptor expression.
AB  - Transcriptional repression of the TGF-beta type II receptor (RII) is one of the
      mechanisms leading to TGF-beta resistance. The newly identified epithelium
      specific ets transcription factor ERT/ESX/ELF-3/ESE-1/jen binds to the TGF-beta
      RII promoter and induces promoter activity. The human gastric cancer cell lines,
      which show undetectable level of TGF-beta RII mRNA, do not express ERT mRNA. To
      study the molecular mechanisms of loss of ERT expression, we have cloned and
      characterized the human ERT promoter. DNA transfection experiments and
      electrophoretic mobility shift assays have revealed the existence of a distinct
      enhancer element (-186 to -177) which we named ESE (ERT promoter specific
      element). Deletion of the ESE markedly decreased expression of the target gene.
      ESE interacts with two distinct nuclear protein complexes, at least one of which
      appears to be inactivated in a cell line which does not express the ERT mRNA,
      compared to a cell line expressing the ERT mRNA. These results suggest the
      possibility that inactivation of the sequence-specific DNA binding protein to the
      region from -186 to -177 contributes to the loss of ERT expression, leading to
      the loss of TGF-beta type II receptor mRNA in human gastric cancer cell lines.

PMID- 11313869
TI  - Alternative splicing of the imprinted candidate tumor suppressor gene ZAC
      regulates its antiproliferative and DNA binding activities.
AB  - ZAC encodes a zinc finger protein with antiproliferative activity, is maternally
      imprinted and is a candidate for the tumor suppressor gene on 6q24. ZAC
      expression is frequently lost in breast and ovary tumor-derived cell lines and
      down-regulated in breast primary tumors. In this report, we describe ZACDelta2,
      an alternatively spliced variant of ZAC lacking the sequence encoding the two N
      terminal zinc fingers. Messenger RNAs encoding ZAC or ZACDelta2 were equally
      abundant and both proteins were nuclear. ZACDelta2 displayed an improved
      transactivation activity and an enhanced affinity for a ZAC binding site,
      suggesting that the two N-terminal zinc fingers negatively regulated ZAC binding
      to its target DNA sequences. Both proteins were equally efficient in preventing
      colony formation, indicating similar overall antiproliferative activities.
      However, these activities resulted from a differential regulation of apoptosis vs
      cell cycle progression since ZACDelta2 was more efficient at induction of cell
      cycle arrest than ZAC, whereas it was the reverse for apoptosis induction. Hence,
      these data further underline that ZAC gene is critically controlled, both at the
      transcriptional level through imprinting and at the functional level through
      alternative splicing.

PMID- 11313870
TI  - Caspase-mediated Cdk2 activation is a critical step to execute transforming
      growth factor-beta1-induced apoptosis in human gastric cancer cells.
AB  - Although TGF-beta1, a growth inhibitor, is known to also induce apoptosis, the
      molecular mechanism of this apoptosis is largely undefined. Here, we identify the
      mechanism of TGF-beta1-induced apoptosis in SNU-16 human gastric cancer cells.
      Cell cycle and TUNEL analysis showed that, upon TGF-beta1 treatment, cells were
      initially arrested at the G1 phase and then driven into apoptosis. Of note,
      caspase-3 was activated in accordance with TGF-beta1-induced G1 arrest. Activated
      caspase-3 is targeted to cleave p21(cip1), p27(kip1), and Rb, which play
      important roles in TGF-beta-induced G1 arrest, into inactive fragments.
      Subsequently, Cdk2 was aberrantly activated due to the cleavage of p21 and p27.
      We found that the inhibition of Cdk2 activity efficiently blocks TGF-beta1
      induced apoptosis, whereas it did not prevent caspase-3 activation or the
      subsequent cleavage of target proteins. In contrast, the suppression of caspase-3
      activity inhibited the cleavage of target proteins, the activation of Cdk2, and
      the induction of apoptosis. Taken together, our results suggest that activation
      of caspase-3 by TGF-beta1 may initiate the conversion from G1 cell cycle arrest
      to apoptosis via the cleavage of p21, p27 and Rb, which in turn causes Cdk2
      activation and, most significantly, Cdk2 activation as a downstream effector of
      caspase is a critical step for the execution of TGF-beta1-induced apoptosis.

PMID- 11313871
TI  - The contribution of the acidic domain of MDM2 to p53 and MDM2 stability.
AB  - p53 and MDM2 are both degraded by the ubiquitin-proteasome pathway. MDM2 binds
      p53 and promotes its rapid degradation. MDM2 is an E3 ligase that activates self
      and p53 ubiquitylation. Moreover, MDM2 nuclear-cytoplasmic shuttling contributes
      to p53 degradation in the cytoplasm. We have identified a new region of MDM2
      which regulates the stability of both p53 and MDM2. The first 50 amino-acids of
      the MDM2 acidic domain (222-272) contribute to MDM2 and MDM2-mediated p53
      degradation by a mechanism which is independent of either MDM2 E3-ligase activity
      or MDM2 nucleo-cytoplasmic shuttling. The transcriptional coactivator p300 could
      have been involved, since it binds to the MDM2 acidic domain. However, we found
      that p300 stabilises MDM2, even in absence of an intact acidic domain, indicating
      that the MDM2 acidic region contributes to proteolysis independently of p300. We
      propose that the MDM2 acidic domain is required for unbiquitylated MDM2 and p53
      to be degraded by cytoplasmic proteasomes.

PMID- 11313872
TI  - Differential effects of Ras signaling through NFkappaB on skeletal myogenesis.
AB  - Oncogenic Ras (H-Ras G12V) inhibits skeletal myogenesis through multiple
      signaling pathways. Previously, we demonstrated that the major downstream
      effectors of Ras (i.e., MEK/MAPK, RalGDS and Rac/Rho) play a minor, if any, role
      in the differentiation-defective phenotype of Ras myoblasts. Recently, NFkappaB,
      another Ras signaling target, has been shown to inhibit myogenesis presumably by
      stimulating cyclin D1 accumulation and cell cycle progression. In this study, we
      address the involvement of NFkappaB activation in the Ras-induced inhibition of
      myogenesis. Using H-Ras G12V and three G12V effector-loop variants, we detect
      high levels of NFkappaB transcriptional activity in C3H10T1/2-MyoD cells treated
      with differentiation medium. Myogenesis is blocked by all Ras proteins tested,
      yet only in the case of H-Ras G12V are cyclin D1 levels increased and cell cycle
      progression maintained. Expression of IkappaBalpha SR, an inhibitor of NFkappaB,
      does not reverse the differentiation-defective phenotype of Ras expressing
      cultures, but does induce differentiation in cultures treated with tumor necrosis
      factor (TNFalpha) or in cultures expressing the RelA/p65 subunit of NFkappaB.
      These data confirm that NFkappaB is a target of Ras and suggest that the cellular
      actions of NFkappaB require additional signals that are discriminated by the Ras
      effector-loop variants. Results with IkappaBalpha SR convincingly demonstrate
      that H-Ras G12V does not rely on NFkappaB activity to block myogenesis, an
      observation that continues to implicate another unidentified signaling pathway(s)
      in the inhibition of skeletal myogenesis by Ras.

PMID- 11313873
TI  - Her-2/neu overexpression induces NF-kappaB via a PI3-kinase/Akt pathway involving
      calpain-mediated degradation of IkappaB-alpha that can be inhibited by the tumor
      suppressor PTEN.
AB  - The Nuclear Factor (NF)-kappaB family of transcription factors controls
      expression of genes which promote cell growth, survival, and neoplastic
      transformation. Recently we demonstrated aberrant constitutive activation of NF
      kappaB in primary human and rat breast cancer specimens and in cell lines.
      Overexpression of the epidermal growth factor receptor (EGFR) family member Her
      2/neu, seen in approximately 30% of breast cancers, is associated with poor
      prognosis. Previously, Her-2/neu has been shown to signal via a
      phosphatidylinositol 3 (PI3)-kinase to Akt/protein kinase B (PKB) pathway. Since
      this signaling pathway was recently shown to activate NF-kappaB, here we have
      tested the hypothesis that Her-2/neu can activate NF-kappaB in breast cancer.
      Overexpression of Her-2/neu and EGFR-4 in Ba/F3 cells led to constitutive PI3-
      and Akt kinase activities, and induction of classical NF-kappaB (p50/p65).
      Similarly, a tumor cell line and tumors derived from MMTV-Her-2/neu transgenic
      mice displayed elevated levels of classical NF-kappaB. Engagement of Her-2/neu
      receptor downregulated the level of NF-kappaB. NF-kappaB binding and activity in
      the cultured cells was reduced upon inhibition of the PI3- to Akt kinase
      signaling pathway via ectopic expression of kinase inactive mutants, incubation
      with wortmannin, or expression of the tumor suppressor phosphatase PTEN.
      Inhibitors of calpain, but not the proteasome, blocked IkappaB-alpha degradation.
      Inhibition of Akt did not affect IKK activity. These results indicate that Her
      2/neu activates NF-kappaB via a PI3- to Akt kinase signaling pathway that can be
      inhibited via the tumor suppressor PTEN, and is mediated by calpain rather than
      the IkappaB kinase complex.

PMID- 11313874
TI  - Gene expression and amplification in breast carcinoma cells with intrinsic and
      acquired doxorubicin resistance.
AB  - The multidrug resistance (MDR) phenotype is a major cause of cancer treatment
      failure. Here the expressions of 4224 genes were analysed for association with
      intrinsic or acquired doxorubicin (DOX) resistance. A cluster of overexpressed
      genes related to DOX resistance was observed. Included in this cluster was ABCB1
      the P-glycoprotein transporter protein gene and MMP1 (Matrix Metalloproteinase
      1), indicative of the invasive nature of resistant cells, and the oxytocin
      receptor (OXTR), a potential new therapeutic target. Overexpression of genes
      associated with xenobiotic transformation, cell transformation, cell signalling
      and lymphocyte activation was also associated with DOX resistance as was estrogen
      receptor negativity. In all carcinoma cells, compared with HBL100 a putatively
      normal breast epithelial cell line, a cluster of overexpressed genes was
      identified which included several keratins, in particular keratins 8 and 18 which
      are regulated through the ras signalling pathway. Analysis of genomic
      amplifications and deletions revealed specific genetic alterations common to both
      intrinsic and acquired DOX resistance including ABCB1, PGY3 (ABCB4) and BAK. The
      findings shown here indicate new possibilities for the diagnosis of DOX
      resistance using gene expression, and potential novel therapeutic targets for
      pharmacological intervention.

PMID- 11313875
TI  - Evidence that wild-type p53 in neuroblastoma cells is in a conformation
      refractory to integration into the transcriptional complex.
AB  - Neuroblastoma (NB) cells reportedly accumulate wild-type p53 exclusively in the
      cytoplasm. However, immunofluorescence assays with five different antibodies
      showed that p53 accumulates in the nucleus of up to 10% of NB cells. PAb1801
      detected cytoplasmic 'punctate structures' which were also found in p53-null
      cells, rendering this antibody unsuitable for p53 detection. A comparison of DO-1
      and PAb1801 staining in NB tissue sections confirmed the results obtained with NB
      cells. Nuclear accumulation of p53 was induced in NB cells using substances which
      disturb p53's tertiary structure at its zinc finger motif, or by treatment with
      mitomycin C. Constitutive nuclear accumulation was observed in an SK-N-SH
      variant, AW-1, which has a point mutation in p53 at Cys176>Ser, disturbing the
      same motif. Even though p53 showed DNA-binding capability after mitomycin C
      treatment of NB cells, the target gene products MDM2 and p21(WAF1,CIP1,SDI1) were
      not synthesized and no p53 transactivating activity measured in a reporter gene
      assay. Therefore we suggest that p53 in NB cells might be predominantly in a
      conformation refractory to integration into the transcriptional complex,
      resulting in at least partial transcriptional inactivity, hyperactive nuclear
      export and resistance to degradation by exogenously expressed MDM2.

PMID- 11313876
TI  - Coexpression of hepatocyte growth factor-Met: an early step in ovarian
      carcinogenesis?
AB  - Since autocrine regulation of HGF-Met is implicated in many forms of human
      cancer, we investigated whether the predisposition to develop ovarian cancer in
      women with hereditary ovarian cancer syndromes involves changes in the expression
      of HGF-Met by the tissue of origin of epithelial ovarian cancers, the ovarian
      surface epithelium (OSE). We compared cultures of normal OSE from women with (FH
      OSE) (n=20) and with no (NFH-OSE) (n=48) family histories of ovarian cancer, SV40
      Tag immortalized OSE lines (IOSE, n=5) and ovarian cancer cell lines (n=3).
      Cultures derived from 21/22 women with NFH-OSE and 13/13 women with FH-OSE
      expressed Met mRNA initially. After two to three passages, Met was downregulated
      in 37% of NFH-OSE cultures but persisted in 100% of FH-OSE cultures and ovarian
      cancer lines, like other epithelial differentiation markers that are stabilized
      in FH-OSE and neoplasia. HGF and Met mRNA were concomitantly expressed by NFH-OSE
      from only three of 32 women but in FH-OSE from eight of 13 women, and also in
      five of five IOSE and two of three ovarian cancer lines. Conditioned media from
      FH-OSE, but not NFH-OSE, contained immunoreactive HGF and induced cohort
      migration which was inhibited by neutralizing HGF antibody. Several signaling
      molecules of the PI3K pathway, including Akt2 and p70 S6K, were constitutively
      activated in FH-OSE from six of six women but in NFH-OSE from only four of eight
      women. Exogenous HGF was mitogenic in OSE, and that effect was regulated through
      the MAP kinase (ERK1/ERK2) and FRAP/p70 S6K pathways. The proliferative response
      to HGF was greater in NFH-OSE than in FH-OSE cultures. The results show that FH
      OSE cultures differ from NFH-OSE by increased stability of Met expression and by
      HGF secretion. Constitutive phosphorylation of kinases and a diminished growth
      response to HGF suggest the presence of autocrine regulation in FH-OSE. In
      analogy with other cell types where an autocrine HGF-Met loop has been implicated
      in tumorigenic transformation, this change in FH-OSE may play a role in the
      enhanced susceptibility to ovarian carcinogenesis in women with hereditary
      ovarian cancer syndromes.

PMID- 11313877
TI  - Xmeis1, a protooncogene involved in specifying neural crest cell fate in Xenopus
      embryos.
AB  - Meis1 (Myeloid Ecotropic viral Integration Site 1) is a homeobox gene that was
      originally isolated as a common site of viral integration in myeloid tumors of
      the BXH-2 recombinant inbred mice strain. We previously isolated a Xenopus
      homolog of Meis1 (Xmeis1). Here we show that Xmeis1 may play a significant role
      in neural crest development. In developing Xenopus embryos, Xmeis1 displays a
      broad expression pattern, but strong expression is observed in tissue of neural
      cell fate, such as midbrain, hindbrain, the dorsal portion of the neural tube,
      and neural crest derived branchial arches. In animal cap explants, overexpression
      of Xmeis1b, an alternatively spliced form of Xmeis1, induces expression of neural
      crest marker genes in the absence of mesoderm. Moreover, Xmeis1b induces XGli-3
      and XZic3, pre-pattern genes involved at the earliest stages of neural crest
      development, and like these two genes, can induce ectopic pigmented cell masses
      when overexpressed in developing embryos. Misexpression of Xmeis1b also induces
      ectopic expression of neural crest markers along the antero-posterior axis of the
      neural tube in developing Xenopus embryos. In contrast, Xmeis1a, another splice
      variant, is much less effective at inducing these effects. These data suggest
      that Xmeis1b is involved in neural crest cell fate specification during
      embryogenesis, and can functionally intersect with the Gli/Zic signal
      transduction pathway.

PMID- 11313878
TI  - Differential expression and regulation of the retinoblastoma family of proteins
      during testicular development and spermatogenesis: roles in the control of germ
      cell proliferation, differentiation and apoptosis.
AB  - Normal spermatogenesis is highly dependent on well-balanced germ cell
      proliferation, differentiation, and apoptosis. However, the molecular mechanisms
      that govern these processes are largely unknown. Retinoblastoma family proteins
      (pRb, p107 and p130) are potentially important regulators of cell growth,
      differentiation and apoptosis. pRb has been shown to be expressed in the rat
      testis and involved in the regulation of spermatogenesis. In the present study,
      the expression and localization of the other two pRb family members, p107 and
      p130, were analysed at both mRNA and protein levels during testicular development
      and spermatogenesis using Northern, Western blotting, immunohistochemistry, and
      in situ hybridization. Furthermore, changes of levels and phosphorylation status
      of pRb family proteins in response to growth suppression and/or apoptosis
      induction were investigated using a seminiferous tubule culture system and three
      animal models. Our data suggest that: (1) pRb family proteins are differentially
      expressed in the rat testis and they function in a cell-type-specific manner
      during testicular development and spermatogenesis; (2) they participate in the
      control of germ cell cycle and act in a cell cycle-phase-specific fashion during
      germ cell proliferation, and (3) they are also involved in the regulation of
      apoptosis of germ cells and Leydig cells.

PMID- 11313879
TI  - c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and
      enhances BRCA1a/1b-mediated growth suppression in breast cancer cells.
AB  - Elk-1, a c-Fos protooncogene regulator, which belongs to the ETS-domain family of
      transcriptional factors, plays an important role in the induction of immediate
      early gene expression in response to a variety of extracellular signals. In this
      study, we demonstrate for the first time the in vitro and in vivo interaction of
      Elk-1 with BRCA1 splice variants BRCA1a and BRCA1b using GST-pull down assays, co
      imunoprecipitations/Western blot analysis of cell extracts from breast cancer
      cells and mammalian two-hybrid assays. We have localized the BRCA1 interaction
      domain of Elk-1 protein to the conserved ETS domain, a motif involved in DNA
      binding and protein-protein interactions. We also observed binding of BRCA1
      proteins to other ETS-domain transcription factors SAP1, ETS-1, ERG-2 and Fli-1
      but not to Elk-1 splice variant DeltaElk-1 and c-Fos protooncogene. Both BRCA1a
      and BRCA1b splice variants function as growth suppressors of human breast cancer
      cells. Interestingly, our studies reveal that although both Elk-1 and SAP-1 are
      highly homologous members of a subfamily of ETS domain proteins called ternary
      complex factors, it is only Elk-1 but not SAP-1 that can augment the growth
      suppressive function of BRCA1a/1b proteins in breast cancer cells. Thus Elk-1
      could be a potential downstream target of BRCA1 in its growth control pathway.
      Furthermore, we have observed inhibition of c-Fos promoter activity in BRCA1a
      transfected stable breast cancer cells and over expression of BRCA1a/1b
      attenuates MEK-induced SRE activation in vivo. These results demonstrate for the
      first time a link between the growth suppressive function of BRCA1a/1b proteins
      and signal transduction pathway involving Elk-1 protein. All these results taken
      together suggest that one of the mechanisms by which BRCA1a/1b proteins function
      as growth/tumor suppressors is through inhibition of the expression of Elk-1
      target genes like c-Fos.

PMID- 11313880
TI  - p53 regulates ceramide formation by neutral sphingomyelinase through reactive
      oxygen species in human glioma cells.
AB  - The present study was designed to elucidate the relationship between p53 and
      ceramide, both of which are involved in apoptotic signaling. Treatment of human
      glioma cells with etoposide caused apoptosis only in cells expressing functional
      p53. p53 activation was followed by the formation of reactive oxygen species
      (ROS), superoxide anion (O2-*) measured by hydroethidium oxidation into ethidium
      and hydrogen peroxide (H2O2) measured by oxidation of 2',7'-dichlorofluorescin
      (DCFH) into 2',7'-dichlorofluorescein (DCF), which was accompanied with ceramide
      generation through the activation of neutral, but not acid, sphingomyelinase.
      Superoxide dismutase (SOD), a selective antioxidant for O2-*, had no effects on
      p53 expression but inhibited ceramide generation and apoptotic cell death caused
      by etoposide. However, catalase, a specific antioxidant for H2O2, only weakly
      inhibited and sodium formate, a hydroxyl radical (* OH) scavenger, unaffected
      etoposide-induced apoptosis. Like etoposide-induced cell death, treatment of
      glioma cells with the O2-*-releasing agent, pyrogallol, induced typical apoptosis
      and ceramide generation even in the presence of catalase. In contrast, human
      glioma cells lacking functional p53, either due to mutation or the expression of
      E6 protein of human papillomavirus, were highly resistant to etoposide and
      exhibited no significant change in the ceramide level. Moreover, expression of
      functional p53 protein in glioma cells expressing mutant p53 using a temperature
      sensitive human p53(Val138) induced ceramide accumulation by the activation of
      neutral sphingomyelinase which was dependent on the generation of O2-*. Taken
      together, these results suggest that p53 may modulate ceramide generation by
      activation of neutral sphingomyelinase through the formation of O2-*, but not its
      downstream compounds H2O2 or * OH.

PMID- 11313881
TI  - Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates
      expression of DNA replication genes including replication protein A2.
AB  - The transcription factor E2F-1 plays a pivotal role in the regulation of G1/S
      transition in higher eukaryotes cell cycle. We used a cell line containing an
      inducible E2F-1 and oligonucleotide microarray analysis to identify novel E2F
      target genes. We show that E2F-1 up-regulates the expression of a number of genes
      coding for components of the DNA replication machinery. Among them is the gene
      coding for the 32 Kd subunit of replication protein A (RPA2). Replication protein
      A is the most abundant single strand DNA binding complex and it is essential for
      DNA replication. We demonstrate that RPA2 is a novel E2F target gene whose
      expression can be directly regulated by E2F-1 via E2F binding sites in its
      promoter. In addition, expression of Topoisomerase IIalpha and subunit IV of DNA
      polymerase alpha is also up-regulated upon E2F-1 induction. Taken together, these
      results provide novel links between components of the DNA replication machinery
      and the cell growth regulatory pathway involving the Rb tumor suppressor and E2F.

PMID- 11313882
TI  - The relative role of ErbB1-4 receptor tyrosine kinases in radiation signal
      transduction responses of human carcinoma cells.
AB  - Activation of the epidermal growth receptor (ErbB1) occurs within minutes of a
      radiation exposure. Immediate downstream consequences of this activation are
      currently indistinguishable from those obtained with growth factors (GF), e.g.
      stimulation of the pro-proliferative mitogen-activated protein kinase (MAPK). To
      identify potential differences, the effects of GFs and radiation on other members
      of the ErbB family have been compared in mammary carcinoma cell lines differing
      in their ErbB expression profiles. Treatment of cells with EGF (ErbB1-specific)
      or heregulin (ErbB4-specific) resulted in a hierarchic transactivations of ErbB2
      and ErbB3 dependent on GF binding specificity. In contrast, radiation
      indiscriminately activated all ErbB species with the activation profile
      reflecting that cell's ErbB expression profile. Downstream consequences of these
      ErbB interactions were examined with MAPK after specifically inhibiting ErbB1 (or
      4) with tyrphostin AG1478 or ErbB2 with tyrphostin AG825. MAPK activation by GFs
      or radiation was completely inhibited by AG1478 indicating total dependance on
      ErbB1 (or 4) depending on which ErbB is expressed. Inhibiting ErbB2 caused an
      enhanced MAPK response simulating an amplified ErbB1 (or 4) response. Thus ErbB2
      is a modulator of ErbB1 (or 4) function leading to different MAPK response
      profiles to GF or radiation exposure.

PMID- 11313883
TI  - A monoclonal antibody against DNA binding helix of p53 protein.
AB  - Three monoclonal antibodies (Mabs) were generated against p53 DNA-binding core
      domain. When tested by immunoprecipitation, Western blot and immunofluorescence
      techniques, Mab 9E4, as well as 7D3 and 6B10 reacted with both wild-type and
      various mutant p53 proteins. The epitopes recognized by Mabs 7D3, 9E4 and 6B10
      were located respectively within the amino acid residues 211-220, 281-290 and 291
      300 of human p53 protein. The epitope recognized by 9E4 Mab coincides with helix
      2, also called p53 DNA binding helix, which allows the direct contact of the
      protein with its target DNA sequences. This antibody may be useful to study
      transcription-dependent and transcription-independent activities of wild-type and
      mutant p53 proteins.

PMID- 11313884
TI  - Two distinct signalling pathways are involved in FGF2-stimulated proliferation of
      choriocapillary endothelial cells: a comparative study with VEGF.
AB  - In the retina, angiogenesis is an important component of normal physiological
      events such as embryonic vascular development. It is also involved in
      pathological processes including diabetic retinopathies and age-related macular
      degeneration, and tumour growth such as choroidal melanoma. Fibroblast growth
      factor (FGF) 2 and vascular endothelial cell growth factor (VEGF) are the two
      major angiogenic factors in the retina. We investigated the mechanism of
      proliferation and the regulation of the mitogenic properties of FGF2 and VEGF in
      cultures of chorocapillary endothelial cells (CEC). FGF2 is a strong mitogen for
      CEC and induced a 2.5-fold increase in cell proliferation after 4 days in culture
      in the absence of serum. In contrast, VEGF is a poor mitogen for CEC. FGF2, but
      not VEGF induces a large activation of MEK1, ERK1/2 and P90(RSK) during CEC
      proliferation. Pharmacological inhibition of Ras processing, and of MEK1 and
      ERK1/2 activation reduced only by 50% FGF2-induced cell proliferation, suggesting
      that there is another signalling pathway for CEC proliferation. Pharmacological
      inhibition of the PI 3-Kinase also inhibits by half FGF2-induced CEC
      proliferation. FGF2 stimulates the activation of the PI 3-K, P70(S6K) and Akt.
      Inhibition of both ERK1/2 and PI 3-K activities suppressed FGF2-induced CEC
      proliferation, demonstrating that CEC proliferation requires both ERKs and PI 3-K
      pathways. These data on the molecular mechanism and signalling may have important
      implications for providing more selective methods for anti-angiogenic and anti
      tumoural therapy.

PMID- 11313885
TI  - Transformation capacities of the papillary renal cell carcinoma-associated
      PRCCTFE3 and TFE3PRCC fusion genes.
AB  - A recurrent chromosomal abnormality associated with a subset of papillary renal
      cell carcinomas is t(X;1)(p11;q21). This translocation leads to the formation of
      two fusion genes, TFE3PRCC and the reciprocal product PRCCTFE3. Both fusion genes
      are expressed in t(X;1)-positive renal cell carcinomas and contain major parts of
      the coding regions of the parental transcription factor PRCC and TFE3 genes,
      respectively. To find out whether these fusion genes possess transforming
      capacity, we transfected NIH3T3 and rat-1 cells with the fusion products, either
      separately or combined. When using soft agar assays, we observed colony formation
      in all cases. NIH3T3 cells transfected with PRCCTFE3 or PRCCTFE3 together with
      TFE3PRCC yielded the highest colony forming capacities. Examination of other
      characteristics associated with malignant transformation, i.e., growth under low
      serum conditions and formation of tumors in athymic nude mice, revealed that
      cells transfected with PRCCTFE3 exhibited all these transformation-associated
      characteristics. Upon transfection of the fusion products into conditionally
      immortalized kidney cells, derived from the proximal tubules of an H-2Kb-tsA58
      transgenic mouse, and consecutive incubation under non-permissive conditions,
      growth arrest was observed, followed by differentiation except for those cells
      transfected with PRCCTFE3. Therefore, we conclude that PRCCTFE3 may be the t(X;1)
      associated fusion product that is most critical for the development of papillary
      renal cell carcinomas.

PMID- 11313886
TI  - Alteration of cell adhesion and cell cycle properties of ES cells by an inducible
      dominant interfering Myb mutant.
AB  - The Myb transcription factors, c-Myb, A-Myb, and B-Myb, regulate cell
      differentiation and/or proliferation. To investigate the role of B-Myb in
      embryogenesis, we introduced an inducible dominant interfering Myb protein (MERT)
      into embryonic stem (ES) cells, which express B-Myb as an exclusive member of Myb
      family. Disruption of normal B-Myb function by the conditional activation of MERT
      caused a drastic morphological alteration of ES cells and G(1)-S cell cycle
      arrest. The inhibition of B-Myb function by MERT dissociated tightly packed ES
      cell colonies into dispersed single cells that subsequently detached from the
      culture dish. Cell adhesion analyses revealed that suppression of B-Myb function
      reduced the adhesion with extracellular matrix proteins, such as laminin,
      collagen, and fibronectin. This reduction was presumably due to decreased cell
      surface expression of beta1 integrin. Embryoid body formation was also severely
      retarded by the activation of MERT. This impairment was attributed to reduced
      expression of E-cadherin, which functions as a homophilic intercellular adhesion
      molecule. Simultaneously, blocking B-Myb function did not alter the expression of
      differentiation markers. Our data indicate that B-Myb plays important roles in
      regulating cell adhesion and cell cycle progression. These results are well
      consistent with the recent report on the phenotype of B-Myb null mice and show
      that the regulation of cell adhesion is an important B-Myb function that has not
      yet been assumed.

PMID- 11313887
TI  - A variant of nuclear localization signal of bipartite-type is required for the
      nuclear translocation of hypoxia inducible factors (1alpha, 2alpha and 3alpha).
AB  - Hypoxia inducible factors (HIF1, 2 and 3), consisting of alpha and beta subunits,
      play an essential role in various responses to hypoxia. Nuclear entry of alpha
      subunits is a necessary step for the formation of DNA-binding complex with beta
      subunit, which is constitutively localized in the nucleus. We show here that the
      nuclear accumulation of HIF2alpha induced by hypoxia is mediated through a novel
      variant of bipartite-type nuclear localization signal (NLS) in the C-terminus of
      the protein, which has an unusual length of spacer sequence between two adjacent
      basic domains. We further show that when the ubiquitin-proteasome system was
      deficient or inhibited, HIF2alpha accumulated in the nucleus even under normoxia,
      also mediated through the bipartite NLS. These findings indicate that the protein
      stability is critical for the nuclear localization of HIF2alpha and hypoxia is
      not a necessary factor for the process. Importantly, the NLS of HIF2alpha is also
      conserved in the other HIF family members, HIF1alpha and HIF3alpha. Mutational
      analyses proved that the NLS mediating the nuclear localization of HIF1alpha is
      indeed bipartite-, but not monopartite-type as thought before. Our results
      suggest that the newly identified NLS is crucial for the functional regulation of
      HIF family.

PMID- 11313888
TI  - Inactivation of p53 tumor suppressor gene acts synergistically with c-neu
      oncogene in salivary gland tumorigenesis.
AB  - Transgenic mice expressing specific oncogenes usually develop tumors in a
      stochastic fashion suggesting that tumor progression is a multi-step process. To
      gain further understanding of the interactions between oncogenes and tumor
      suppressor genes during tumorigenesis, we have crossed a transgenic strain
      (TG.NK) carrying an activated c-neu oncogene driven by the MMTV enhancer/promoter
      with p53-deficient mice. c-neu transgenic mice have stochastic breast tumor
      formation and normal appearing salivary glands. However, c-neu mice heterozygous
      for a p53 deletion develop parotid gland tumors and loose their wild type p53
      allele. c-neu mice with a homozygous p53 deletion have increased rates of parotid
      tumor onset suggesting that inactivation of p53 is required and sufficient for
      parotid gland transformation in the presence of activated c-neu. In contrast to
      the dramatic effect of p53 in parotid gland transformation, p53 loss has little
      effect on the rate or stochastic appearance of mammary tumors. In addition, p53
      loss was accompanied by the down regulation of p21 in parotid gland tumors but
      not breast tumors. The parotid gland tumors were aneuploid and demonstrated
      increased levels of Cyclin D1 expression. These observations suggest that in c
      neu transgenic mice, p53 alterations have differential tissue effects and may be
      influenced by the tissue specific expression of genes influencing p53 activity.

PMID- 11313889
TI  - PTOV1, a novel protein overexpressed in prostate cancer containing a new class of
      protein homology blocks.
AB  - In a search for molecular markers of progression in prostate cancer by means of
      differential display, we have identified a new gene, which we have designated
      PTOV1. Semiquantitative RT-PCR has established that nine out of 11 tumors
      overexpress PTOV1 at levels significantly higher than benign prostatic
      hyperplasia or normal prostate tissue. The human PTOV1 protein consists almost
      entirely of two repeated blocks of homology of 151 and 147 amino acids, joined by
      a short linker peptide, and is encoded by a 12-exon gene localized in chromosome
      19q13.3. A Drosophila melanogaster PTOV1 homolog also contains two tandemly
      arranged PTOV blocks. A second gene, PTOV2, was identified in humans and
      Drosophila, coding for proteins with a single PTOV homology block and unrelated
      amino- and carboxyl-terminal extensions. A 1.8-Kb PTOV1 transcript was detected
      abundantly in normal human brain, heart, skeletal muscle, kidney and liver, and
      at low levels in normal prostate. Immunocytochemical analysis and expression of
      chimeric GFP-PTOV1 proteins in cultured cells showed a predominantly perinuclear
      localization of PTOV1. In normal prostate tissue and in prostate adenomas, PTOV1
      was undetectable or expressed at low levels, whereas nine out of 11 prostate
      adenocarcinomas showed a strong immunoreactivity, with a focal distribution in
      areas of carcinoma and prostatic intraepithelial neoplasia. Therefore, PTOV1 is a
      previously unknown gene, overexpressed in early and late stages of prostate
      cancer. The PTOV homology block represents a new class of conserved sequence
      blocks present in human, rodent and fly proteins.

PMID- 11313890
TI  - Src family kinases and HER2 interactions in human breast cancer cell growth and
      survival.
AB  - Evidence from murine fibroblast models and human breast cancer cells indicates
      that c-Src and human EGF receptor (HER1) synergize to enhance neoplastic growth
      of mammary epithelial cells. To investigate whether interactions between c-Src
      and other HER family members may also play a role in breast tumor progression, we
      characterized 13 human breast carcinoma cell lines and 13 tumor samples for
      expression of HER family members and c-Src and examined a subset of the cell
      lines for Src-dependent, heregulin (HRG)-augmented, anchorage-dependent and
      independent growth. By immunoblotting, we found that all cell lines overexpressed
      one or more HER family member, and 60% overexpressed c-Src. Seventy-five per cent
      of the tumor tissues overexpressed HER2, while 64% overexpressed c-Src. Colony
      formation in soft agar was enhanced by HRG in three of five cell lines tested, a
      response that correlated with the presence of a c-Src/HER2 heterocomplex. This
      result suggests that HRG may act through both HER2 and c-Src to facilitate
      anchorage-independent growth. In contrast, HRG had little effect on anchorage
      dependent growth in any of the cell lines tested. PP1, a Src family kinase
      inhibitor, reduced or ablated HRG-dependent and independent soft agar growth or
      anchorage dependent growth, and triggered apoptosis in all cell lines tested. The
      apoptotic effect of PP1 could be partially or completely reversed by HRG,
      depending on the cell line. These results suggest that while Src family kinases
      may cooperate with HRG to promote the survival and growth of human breast tumor
      cells, they also function independently of HER2/HRG in these processes.

PMID- 11313891
TI  - Sodium nitroprusside enhances TRAIL-induced apoptosis via a mitochondria
      dependent pathway in human colorectal carcinoma CX-1 cells.
AB  - The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo-2L) is a
      recently characterized member of the family of programmed cell death-inducing
      ligands that includes TNF-alpha and CD95L (FasL). It is well known that TRAIL
      binds to the death signaling receptors, DR4 and DR5, and initiates the TRAIL
      death pathway. Activation of this pathway, mediated through a caspase cascade,
      causes apoptosis. In this study, we hypothesized that oxidative stress
      facilitates TRAIL-induced apoptosis by promoting caspase activity through
      cytochrome c release from mitochondria. Human colorectal carcinoma CX-1 cells
      were treated with various concentrations of TRAIL (12.5-200 ng/ml) and/or sodium
      nitroprusside (SNP; 0.03-1 mM) for 12 h. SNP, a nitric oxide donor, which had
      little toxic effect by itself, enhanced TRAIL-induced cytotoxicity. For example,
      TRAIL-induced apoptosis (200 ng/ml) was increased by a factor of 2.5-fold in the
      presence of 1 mM SNP. The combined treatment also caused an increase in
      cytochrome c release, caspase-3 activity, and PARP cleavage. Overexpression of
      Bcl-2 completely blocked the SNP-promoting effects, but only moderately inhibited
      TRAIL-induced apoptosis. Similar results were observed in the presence of
      hydrogen peroxide or peroxynitrite. Taken together, the present studies suggest
      that SNP enhances TRAIL-induced cytotoxicity by facilitating the mitochondria
      mediated caspase signal transduction pathway.

PMID- 11313892
TI  - Elevated superoxide production by active H-ras enhances human lung WI-38VA-13
      cell proliferation, migration and resistance to TNF-alpha.
AB  - Accumulating evidence has suggested that cellular production of superoxide acts
      as an intracellular messenger to regulate gene expression and modulate cellular
      activities. In this report, we set out to investigate the role of active H-ras
      mediated superoxide production on tumor cell malignancy in a SV-40 transformed
      human lung WI-38 VA-13 cell line. Stable transfection and expression of
      constitutively active mutant V12-H-ras (V12-H-ras) dramatically increased
      intracellular production of superoxide. The expression of V12-H-ras significantly
      enhanced cell proliferation, migration and resistance to TNF-alpha treatment
      compared to that of parental and vector control cells, while expression of wild
      type H-ras (WT-H-ras) only had modest effects. Upon scavenging by superoxide
      dismutase and other molecules that decrease the intracellular level of active H
      ras mediated superoxide production, cell proliferation, migration and resistance
      to TNF-alpha were significantly reduced. Furthermore, we demonstrated that the
      activation of membrane NADPH oxidase activity by expression of active H-ras
      contributed to the intracellular superoxide production. The causal relationship
      between membrane superoxide production and increased cell proliferation,
      migration, and resistance to TNF-alpha by the expression of active H-ras, has
      provided direct evidence to demonstrate that superoxide acts as an intracellular
      messenger to cascade ras oncogenic signal relay and to modulate tumor malignant
      activity.

PMID- 11313893
TI  - Telomeric protein Pin2/TRF1 induces mitotic entry and apoptosis in cells with
      short telomeres and is down-regulated in human breast tumors.
AB  - Telomeres are essential for cell survival and have been implicated in the mitotic
      control. The telomeric protein Pin2/TRF1 controls telomere elongation and its
      expression is tightly regulated during cell cycle. We previously reported that
      overexpression of Pin2/TRF1 affects mitotic progression. However, the role of
      Pin2/TRF1 at the interface between cell division and cell survival remains to be
      determined. Here we show that overexpression of Pin2 induced apoptosis in cells
      containing short telomeres, but not in cells with long telomeres. Furthermore,
      before entering apoptosis, Pin2-expressing cells first accumulated in mitosis and
      strongly stained with the mitosis-specific MPM2 antibody. Moreover, Pin2-induced
      apoptosis is potentiated by arresting cells in mitosis, but suppressed by
      accumulating cells in G1. In addition, overexpression of Pin2 also resulted in
      activation of caspase-3, and its proapoptotic activity was significantly reduced
      by inhibition of caspase-3. These results indicate that up-regulation of
      Pin2/TRF1 can specifically induce entry into mitosis and apoptosis, likely via a
      mechanism related to activation of caspase-3. Significantly, we also found that,
      out of 51 human breast cancer tissues and 10 normal controls examined, protein
      levels of Pin2/TRF1 in tumors were significantly lower than in normal tissues, as
      detected by immunoblotting analysis and immunocytochemistry. Since down
      regulation of Pin2/TRF1 allows cells to maintain long telomeres, these results
      suggest that down-regulation of Pin2/TRF1 may be important for cancer cells to
      extend their proliferative potential.

PMID- 11313895
TI  - An hsRPB4/7-dependent yeast assay for trans-activation by the EWS oncogene.
AB  - Chromosomal fusions of the N-terminal region of the Ewings Sarcoma Oncogene (EWS
      Activation-Domain, EAD) to the DNA-binding domains of a variety of cellular
      transcription factors, produce oncogenic proteins (EWS-fusion proteins (EFPs))
      that cause a variety of malignancies. The EAD can act as a potent transcriptional
      activation domain and is required for the oncogenic activity of EFPs. Previous
      studies demonstrating a physical interaction between the EAD and the human RNA
      Polymerase II subunit hsRPB7 suggest a crucial role for RPB7 and its partner,
      RPB4, in EAD function. Homologues of hsRPB4/7 exist in S. cerevisiae, and here we
      describe an RPB4/7-dependent yeast assay for EAD-mediated trans-activation.
      Conditional yeast strains lacking RPB4 are defective for trans-activation by a
      Gal4/EAD fusion protein at the permissive temperature. Introduction of hsRPB4
      alone is unable to rescue trans-activation, while a combination of hsRPB4 and
      hsRPB7 significantly rescues activity. These findings provide the first
      functional evidence for a direct role of the RPB4/7 complex in EAD-mediated trans
      activation. In addition, the yeast assay provides a tractable system for further
      molecular analysis of EAD and RPB4/7 action.

PMID- 11313894
TI  - Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast
      and ovarian tumours.
AB  - Previously we analysed overlapping homozygous deletions in lung and breast
      tumours/tumour lines and defined a small region of 120 kb (part of LCTSGR1) at
      3p21.3 that contained putative lung and breast cancer tumour suppressor gene(s)
      (TSG). Eight genes including RASSF1 were isolated from the minimal region.
      However, extensive mutation analysis in lung tumours and tumour lines revealed
      only rare inactivating mutations. Recently, de novo methylation at a CpG island
      associated with isoform A of RASSF1 (RASSF1A) was reported in lung tumours and
      tumour lines. To investigate RASSF1A as a candidate TSG for various cancers, we
      investigated: (a) RASSF1A methylation status in a large series of primary tumour
      and tumour lines; (b) chromosome 3p allele loss in lung tumours and (c) RASSF1
      mutation analysis in breast tumours. RASSF1A promoter region CpG island
      methylation was detected in 72% of SCLC, 34% of NSCLC, 9% of breast, 10% of
      ovarian and 0% of primary cervical tumours and in 72% SCLC, 36% NSCLC, 80% of
      breast and 40% of ovarian tumour lines. In view of the lower frequency of RASSF1
      methylation in primary breast cancers we proceeded to RASSF1 mutation analysis in
      40 breast cancers. No mutations were detected, but six single nucleotide
      polymorphisms were identified. Twenty of 26 SCLC tumours with 3p21.3 allelic loss
      had RASSF1A methylation, while only six out of 22 NSCLC with 3p21.3 allele loss
      had RASSF1A methylation (P=0.0012), one out of five ovarian and none out of six
      cervical tumours with 3p21.3 loss had RASSF1A methylation. These results suggest
      that (a) RASSF1A inactivation by two hits (methylation and loss) is a critical
      step in SCLC tumourigenesis and (b) RASSF1A inactivation is of lesser importance
      in NSCLC, breast, ovarian and cervical cancers in which other genes within
      LCTSGR1 are likely to be implicated.

PMID- 11313896
TI  - E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse
      gastric carcinoma.
AB  - In diffuse gastric carcinoma, despite common E-cadherin gene (CDH1) mutations,
      tumors show absence of CDH1 loss of heterozigosity (LOH) in most cases. This
      observation challenges the classical two-hit model of tumor suppressor gene
      inactivation. In order to investigate whether or not CDH1 promoter methylation
      may function as the second hit we analysed a series of 23 sporadic gastric
      carcinomas for the presence of CDH1 mutations, CDH1 promoter methylation, LOH and
      E-cadherin expression. CDH1 mutations were detected in nine of the 16 (56.3%)
      diffuse gastric carcinomas and in none of the seven intestinal gastric
      carcinomas. In diffuse gastric carcinomas harboring CDH1 mutations, LOH was
      observed in a single case. Loss of plasma membrane E-cadherin expression was
      consistently found in all nine cases with CDH1 mutation, suggesting that tumors
      inactivated the remaining CDH1 allele via a different mechanism. CDH1 promoter
      methylation was observed in nine of the 16 (56.3%) diffuse-type gastric carcinoma
      cases, including six of the nine cases (66.7%) harboring CDH1 mutations. CDH1
      promoter methylation was also seen in two (28.6%) intestinal-type cases. Our
      results show that CDH1 promoter methylation is the second hit in more than half
      of the sporadic diffuse gastric carcinoma cases harboring CDH1 mutations.

PMID- 11313899
TI  - New mechanisms in heptahelical receptor signaling to mitogen activated protein
      kinase cascades.
AB  - Activation of classical second messenger cascades cannot fully explain the
      recently appreciated roles of heptahelical, or G-protein coupled receptors
      (GPCRs), in stimulation of mitogen activated protein kinase (MAPK) cascades.
      Rather, several distinct signaling mechanisms appear to contribute to GPCR
      mediated MAPK activation. These include transactivation of the Epidermal Growth
      Factor Receptor (EGFR) via the autocrine/paracrine release of EGF-like ligands at
      the cell surface and scaffolding of MAPK cascades. A significant advance in the
      understanding of how GPCRs activate MAPK cascades is the discovery that beta
      arrestin, a protein well known for its roles in both receptor desensitization and
      internalization, serves as a scaffolding protein for at least two GPCR stimulated
      MAPK cascades, the extracellular signal regulated kinase (ERK) cascade and the c
      jun N-terminal kinase 3 (JNK3) cascade. Together, these novel mechanisms of GPCR
      mediated MAPK regulation may permit GPCRs in specific situations to control the
      temporal and spatial activity of MAPKs and thereby determine the consequences of
      GPCR stimulation with respect to transcriptional activation, cell proliferation
      and apoptosis.

PMID- 11313900
TI  - Ras-MAP kinase signaling by lysophosphatidic acid and other G protein-coupled
      receptor agonists.
AB  - Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are extracellular
      lipid mediators that signal through distinct members of the Edg/LP subfamily of G
      protein-coupled receptors (GPCRs). LPA and S1P receptors are expressed in almost
      every cell type and can couple to multiple G proteins (G(i), G(q) and G(12/13))
      to mediate a great variety of responses, ranging from rapid morphological changes
      to long-term stimulation of cell proliferation. LPA serves as the prototypic GPCR
      agonist that activates the small GTPases Ras (via G(i)) and RhoA (via G(12/13)),
      leading to activation of the mitogen-activated protein kinase (MAPK) cascade and
      reorganization of the actin cytoskeleton, respectively. This review focuses on
      our current insights into how Ras-MAPK signaling is regulated by GPCR agonists in
      general, and by LPA in particular.

PMID- 11313901
TI  - Rho GTPase-dependent transformation by G protein-coupled receptors.
AB  - G protein coupled receptors (GPCRs) constitute the largest family of cell surface
      receptors, with more than 1000 members, and are responsible for converting a
      diverse array of extracellular stimuli into intracellular signaling events. Most
      members of the family have defined roles in intermediary metabolism and generally
      perform these functions in well-differentiated cells. However, there is an
      increasing awareness that some GPCRs can also regulate proliferative signaling
      pathways and that chronic stimulation or mutational activation of receptors can
      lead to oncogenic transformation. Activating mutations in GPCRs are associated
      with several types of human tumors and some receptors exhibit potent oncogenic
      activity due to agonist overexpression. Additionally, expression screening
      analyses for novel oncogenes identified GPCRs whose expression causes the
      oncogenic transformation of NIH3T3 mouse fibroblasts. These include Mas, G2A, and
      the PAR-1 thrombin receptor. In this review we summarize the signaling and
      transforming properties of these GPCR oncoproteins. What has emerged from these
      studies is the delineation of a GTPase cascade where transforming GPCRs cause
      aberrant growth regulation via activation of Rho family small GTPases.

PMID- 11313902
TI  - Angiogenesis and G-protein-coupled receptors: signals that bridge the gap.
AB  - Angiogenesis is a mechanism that has repercussions in a number of physiological
      and pathological situations. Vascular endothelial growth factor and basic
      fibroblast growth factor have understandably received enormous research coverage
      for being the major mediators of new blood vessel growth, often overshadowing
      other agonist that also have strong angiogenic potential. We wish to put the
      spotlight on GPCR agonists that undoubtedly have their word to say on the subject
      of angiogenesis. In this short review, we will discuss our findings along with
      the work from other groups on the mechanisms by which GPCR agonists, like
      thrombin and angiotensin II, control a number of angiogenic signals. A complete
      understanding of these mechanisms could, by the design of new therapeutic
      strategies, have a strong impact in clinical oncology.

PMID- 11313903
TI  - Autocrine and paracrine signaling through neuropeptide receptors in human cancer.
AB  - Autocrine and paracrine signaling leading to stimulation of tumor cell growth is
      a common theme in human cancers. In addition to polypeptide growth factors such
      as EGF family members which signal through receptor tyrosine kinases,
      accumulating evidence supports the autocrine and paracrine involvement of
      specific neuropeptides with defined physiologic actions as neurotransmitters and
      gut hormones in lung, gastric, colorectal, pancreatic and prostatic cancers.
      These neuropeptides, including gastrin-releasing peptide, neuromedin B,
      neurotensin, gastrin, cholecystokinin and arginine vasopressin bind seven
      transmembrane-spanning receptors that couple to heterotrimeric G proteins.
      Studies with human small cell lung cancer (SCLC) cells support a requirement for
      balanced signaling through G(q) and G(12/13) proteins leading to intracellular
      Ca2+ mobilization, PKC activation and regulation of the ERK and JNK MAP kinase
      pathways. While specific neuropeptide antagonists offer promise for interrupting
      the single neuropeptide autocrine systems operating in pancreatic and prostatic
      cancers, SCLC is exemplified by multiple, redundant neuropeptide autocrine
      systems such that tumor growth cannot be inhibited with a single specific
      antagonist. However, a novel class of neuropeptide derivatives based on the
      substance P sequence have been defined that exhibit broad specificity for
      neuropeptide receptors and induce apoptosis in SCLC by functioning as biased
      agonists that stimulate discordant signal transduction. Thus, interruption of
      autocrine and paracrine neuropeptide signaling with specific antagonists or broad
      spectrum biased agonists offer promising new therapeutic approaches to the
      treatment of human cancers.

PMID- 11313904
TI  - Protease activated receptors: theme and variations.
AB  - The four PAR family members are G protein coupled receptors that are normally
      activated by proteolytic exposure of an occult tethered ligand. Three of the
      family members are thrombin receptors. The fourth (PAR2) is not activated by
      thrombin, but can be activated by other proteases, including trypsin, tryptase
      and Factor Xa. This review focuses on recent information about the manner in
      which signaling through these receptors is initiated and terminated, including
      evidence for inter- as well as intramolecular modes of activation, and continuing
      efforts to identify additional, biologically-relevant proteases that can activate
      PAR family members.

PMID- 11313905
TI  - Virally encoded 7TM receptors.
AB  - A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of
      which clearly are derived from their host chemokine system as well as induce high
      expression of certain 7TM receptors in the infected cells. The receptors appear
      to be exploited by the virus for either immune evasion, cellular reprogramming,
      tissue targeting or for cell entry. Through their efficient evolutionary
      machinery and through in vivo selection performed directly on the human cellular
      and molecular targets, virus have been able to optimize the encoded receptors for
      distinct pharmacological profiles to help in various parts of the viral life
      cyclus. Most of the receptors encoded by human pathogenic virus are still orphan
      receptors, i.e. the endogenous ligand is unknown. In the few cases where it has
      been possible to characterize these receptors pharmacologically, they have been
      found to bind a broad spectrum of either CC chemokines, US28 from human
      cytomegalovirus, or CXC chemokines, ORF74 from human herpesvirus 8. Nevertheless,
      US28 has been specifically optimized for recognition of the membrane bound
      chemokine, fractalkine, conceivably involved in cell-cell transfer of virus;
      whereas ORF74 among the endogenous CXC chemokines has selected angiogenic
      chemokines as agonists and angiostatic/modulatory chemokines as inverse agonists.
      ORF74 possess substantial cell-transforming properties and signals with high
      constitutive activity through the phospholipase C and MAP kinase pathways.
      Interestingly, transgenic expression of this single gene in certain lymphocyte
      cell lineages leads to the development of lesions which are remarkably similar to
      Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other
      virally encoded 7TM receptors appear to be attractive future drug targets.

PMID- 11313906
TI  - Cell communication networks: epidermal growth factor receptor transactivation as
      the paradigm for interreceptor signal transmission.
AB  - Communication between different cellular signaling systems has emerged as a
      common principle that enables cells to integrate a multitude of signals from its
      environment. Transactivation of the epidermal growth factor receptor (EGFR)
      represents the paradigm for cross-talk between G protein-coupled receptors
      (GPCRs) and receptor tyrosine kinases (RTKs). The recent identification of Zn2+
      dependent metalloproteinases and transmembrane growth factor precursors as
      critical elements in GPCR-induced EGFR transactivation pathways has defined new
      components of a cellular communication network of rapidly increasing complexity.
      Further elucidation of the molecular details of the EGFR transactivation
      mechanism will provide new understanding of its relevance for normal
      physiological processes and their pathophysiological deviations.

PMID- 11313907
TI  - G protein coupled receptor signaling through the Src and Stat3 pathway: role in
      proliferation and transformation.
AB  - Extracellular signals when routed through signaling pathways that use
      heterotrimeric G proteins can engage multiple signaling pathways leading to
      diverse biological consequences. One locus at which signal sorting occurs is at
      the level of G proteins. G protein alpha-subunits appear to be capable of
      interacting with different effectors leading to engagement of distinct signaling
      pathways. Regulation of different pathways in turn leads to different biological
      outcomes. The process of neoplastic transformation is controlled to a large
      extent through the activation and inhibition of signaling pathways. Signaling
      pathways such as the Ras-MAPK, v-Src-Stat3 pathways are activated in the process
      of transformation. Expression of activated Galpha subunits have been shown to
      cause transformation of cells. While activation of the MAPK 1,2 pathway by
      various Galpha subunits has been reported for several years, recent studies show
      the activation and involvement of Src and Stat3 pathways in Galphao and Galphai
      mediated transformation of cells. Recent studies also suggest that both Galphai
      and Galphas may be able to interact with and activate Src. The activation of Src
      and Stat3 by G proteins has also been demonstrated by ligand-induced activation
      of G protein receptors. So increasingly it is becoming clear that the Src and
      Stat3 pathways are potential effectors for G proteins and that they may play a
      role in G protein function.

PMID- 11313908
TI  - Transforming G proteins.
AB  - Heterotrimeric guanine nucleotide binding proteins, commonly known as G proteins
      form a super-family of signal transduction proteins. They are peripherally
      associated with the plasma membrane and provide signal coupling to seven
      transmembrane surface receptors. G proteins are composed of monomers of alpha,
      beta, and gamma subunits. The beta- and gamma-subunits are tightly associated.
      The receptors activated by the appropriate "signal", interact catalytically with
      specific G-proteins to mediate guanine nucleotide exchange at the GDP/GTP binding
      site of the G-protein alpha-subunits, thus displacing the bound GDP for GTP. The
      GTP bound form of the g-protein alpha-subunit and in some cases the free
      betagamma-subunits initiate cellular response by altering the activity of
      specific effector molecules. Recent studies have indicated that the asyncronous
      activation of these proteins can lead to the oncogenic transformation of
      different cell types. The mechanism by which G-proteins regulate the various cell
      functions appear to involve a complex net-working between different signaling
      pathways. This review summarizes the signaling mechanisms involved in the
      regulation of cell proliferation by these transforming G proteins.

PMID- 11313909
TI  - G(z) signaling: emerging divergence from G(i) signaling.
AB  - A large variety of neurotransmitters, hormones, and chemokines regulate cellular
      functions via cell surface receptors that are coupled to guanine nucleotide
      binding regulatory proteins (G proteins) belonging to the G(i) subfamily. All
      members of the G(i) subfamily, with the sole exception of G(z), are substrates
      for the pertussis toxin ADP-ribosyl transferase. G(z) also exhibits unique
      biochemical and regulatory properties. Initial portrayals of the cellular
      functions of G(z) bear high resemblance to those of other G(i) proteins both in
      terms of the receptors and effectors linked to G(z). However, recent discoveries
      have begun to insinuate a distinct role for G(z) in cellular communication.
      Functional interactions of the alpha subunit of G(z) (Galpha(z)) with the NKR-P1
      receptor, Galpha(z)-specific regulator of G protein signaling, p21-activated
      kinase, G protein-regulated inducers of neurite outgrowth, and the Eya2
      transcription cofactor have been demonstrated. These findings provide possible
      links for G(z) to participate in cellular development, survival, proliferation,
      differentiation and even apoptosis. In this review, we have drawn a sketch of a
      signaling network with G(z) as the centerpiece. The emerging picture is one that
      distinguishes G(z) from other members of the G(i) subfamily.

PMID- 11313910
TI  - G-proteins in growth and apoptosis: lessons from the heart.
AB  - The acute contractile function of the heart is controlled by the effects of
      released nonepinephrine (NE) on cardiac adrenergic receptors. NE can also act in
      a more chronic fashion to induce cardiomyocyte growth, characterized by cell
      enlargement (hypertrophy), increased protein synthesis, alterations in gene
      expression and addition of sarcomeres. These responses enhance cardiomyocyte
      contractile function and thus allow the heart to compensate for increased stress.
      The hypertrophic effects of NE are mediated through Gq-coupled alpha(1)
      adrenergic receptors and are mimicked by the actions of other neurohormones
      (endothelin, prostaglandin F(2alpha) angiotensin II) that also act on Gq-coupled
      receptors. Activation of phospholipase C by Gq is necessary for these responses,
      and protein kinase C and MAP kinases have also been implicated. Gq stimulated
      cardiac hypertrophy is also evident in transgenic mouse models. In contrast,
      stimulation of G(s)-coupled beta-adrenergic receptors or G(i)-coupled receptors
      do not directly effect cardiomyocyte hypertrophy. Apoptosis is also induced by G
      protein-coupled receptor stimulation in cardiomyocytes. Sustained or excessive
      activation of either Gq- or Gs-signaling pathways results in apoptotic loss of
      cardiomyocytes both in vitro and in vivo. Apoptosis is associated with decreased
      ventricular function in the failing heart. Cardiomyocytes provide an ideal model
      system for understanding the basis for G-protein mediated hypertrophy and
      apoptosis, and the mechanisms responsible for the transition from compensatory to
      deleterious levels of signaling. This information may prove critical for
      designing interventions that prevent the pathophysiological consequences of heart
      failure.

PMID- 11313911
TI  - In vivo functions of heterotrimeric G-proteins: studies in Galpha-deficient mice.
AB  - Heterotrimeric guanine nucleotide binding proteins (G-proteins) mediate the
      effects of numerous hormones, neurotransmitters or sensory stimuli by coupling
      their transmembranous receptors to various effectors like enzymes and ion
      channels. Changes in the activity of these effector molecules eventually lead to
      the regulation of multiple cellular functions ranging from short term regulatory
      processes like the control of secretion rates, muscle tonus or metabolic
      processes to long term effects like regulation of growth and differentiation.
      Heterotrimeric G-proteins play a pivotal role in this transmembrane signaling
      process as they take part in processing and sorting of incoming signals as well
      as in adjusting the sensitivity of the system. This review describes some of the
      new insights into the biological role of G-protein mediated signaling processes
      provided by the analysis of mice genetically engineered to lack distinct G
      protein alpha-subunits.

PMID- 11313912
TI  - Regulation of G proteins by covalent modification.
AB  - Heterotrimeric G protein alpha,beta, and gamma subunits are subject to several
      kinds of co- and post-translational covalent modifications. Among those relevant
      to G protein-coupled receptor signaling in normal cell function are lipid
      modifications and phosphorylation. N-myristoylation is a co-translational
      modification occurring for members of the G(i) family of Galpha subunits, while
      palmitoylation is a post-translational modification that occurs for these and
      most other Galpha subunits. One or both modifications are required for plasma
      membrane targeting and contribute to regulating strength of interaction with the
      Gbetagamma heterodimer, effectors, and regulators of G protein signaling (RGS
      proteins). Galpha subunits, including those with transforming activity, are often
      inactive when unable to be modified with lipids. The reversible nature of
      palmitoylation is intriguing in this regard, as it lends itself to a regulation
      integrated with the activation state of the G protein. Several Galpha subunits
      are substrates for phosphorylation by protein kinase C and at least one is a
      substrate for phosphorylation by the p21-activated protein kinase.
      Phosphorylation in both instances inhibits the interactions of these subunits
      with the Gbetagamma heterodimer and RGS proteins. Several Galpha subunits are
      also substrates for tyrosine phosphorylation. A Ggamma subunit is phosphorylated
      by protein kinase C, with the consequence that it interacts more tightly with a
      Galpha subunit but less well with an effector.

PMID- 11313913
TI  - Heterotrimeric G-protein betagamma-dimers in growth and differentiation.
AB  - Heterotrimeric G-proteins are components of the signal transduction pathways for
      the soluble and cell-contact signals that regulate normal growth and
      differentiation. There is now a greater appreciation of the role of the
      Gbetagamma-dimer in the regulation of a variety of intracellular effectors,
      including ion channels, adenylyl cyclase, and phospholipase Cbeta. In many cases,
      Gbetagamma-dimers are required for the activation of mitogen activated protein
      kinase (MAPK) pathways that promote cellular proliferation, although the
      underlying mechanisms have yet to be fully elucidated. Activation of
      phosphotidylinositol-3-kinase (PI3K) is a critical step in the intracellular
      transduction of survival signals. Gbetagamma-dimers directly activate PI3Kgamma
      as well as the more widely distributed PI3Kbeta. The activation of PI3Kgamma by
      Gbetagamma-dimers likely involves direct binding of specific Gbetagamma-dimers to
      both subunits of PI3Kgamma. Thus, Gbetagamma-dimers transmit signals from
      numerous receptors to a variety of intracellular effectors in distinct cellular
      contexts. Five distinct Gbeta-subunits and 12 distinct Ggamma-subunits have been
      identified. New experimental approaches are needed to elucidate the specific
      roles of individual Gbetagamma-dimers in the pathways that transduce signals for
      proliferation and survival.

PMID- 11313914
TI  - RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?

PMID- 11313915
TI  - Tumour suppressor p53 inhibits human fibroblast growth factor 2 expression by a
      post-transcriptional mechanism.
AB  - Fibroblast growth factor-2 (FGF-2) is a powerful mitogen and angiogenic factor
      whose expression is strongly regulated at the translational level. The
      constitutive upregulation of FGF-2 isoforms in transformed cells prompted us to
      investigate the post-transcriptional effects of a tumour suppressor, p53, on FGF
      2 expression. We show here in human primary skin fibroblasts that the cell
      density-dependent variation of FGF-2 mRNA translatability was inversely
      correlated with endogenous p53 expression. Transient cell transfection revealed
      an inhibitory effect of wild-type p53 on the expression of chimeric FGF--CAT
      proteins. RNAse mapping experiments ruled out any effect of p53 on FGF--CAT mRNA
      accumulation, suggesting a translational inhibition. This inhibition was mediated
      by the FGF-2 mRNA leader, but not by vascular endothelial growth factor or
      platelet derived growth factor mRNA leaders. Neither p53-like protein p73, nor
      p21/waf had any inhibitory activity. Furthermore a set of hot spot mutants of p53
      bearing mutations in the DNA binding domain had no post-transcriptional
      inhibitory effect. In contrast a p53 mutant of the transactivating domain was
      still able to block FGF--CAT expression, indicating that the post-transcriptional
      activity of p53 described here was independent of the trans-activation of target
      genes. Such data reveal a novel mechanism by which p53 efficiently blocks the
      expression of a major proliferating, anti-apoptotic and angiogenic gene.

PMID- 11313916
TI  - Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in
      small cell lung carcinoma.
AB  - The transcription factor E2F1 is a key component of cell cycle that acts to
      transactivate genes required for S phase entry. Thus, it plays an important role
      in cellular proliferation, oncogenesis and differentiation. In order to
      investigate its potential implication in human lung carcinogenesis, we studied
      E2F1 protein expression by Western blotting and immunohistochemistry in a series
      of 58 human lung tumours of all histological types. We showed that E2F1 product
      was overexpressed in 92% (24/26) of small cell lung carcinoma (SCLC) and in 50%
      (5/10) of large cell neuroendocrine carcinoma (LCNEC) whereas it was undetectable
      in 90% (10/11) of adenocarcinoma and 82% (9/11) of squamous carcinoma when
      compared to corresponding normal lung. No amplification was found but an increase
      in E2F1 mRNA expression was detected in 75% (18/24) of SCLC overexpressing E2F1
      product. In these tumours and in contrast with NSCLC, upregulation of E2F1
      product was associated with its nuclear accumulation and with overexpression of
      several of its target-genes. Moreover, E2F1 overexpression in NE lung tumours was
      significantly associated with a high KI67 index (P<0.0001) as well as a Bcl-2:Bax
      ratio >1 (P<0.001). Overall, these results demonstrate a distinct pattern of E2F1
      expression in human lung tumours and suggest that its deregulation could be
      involved in the carcinogenesis of SCLC.

PMID- 11313918
TI  - Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor
      kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes.
AB  - Immune cell-specific adaptor proteins create various combinations of multiprotein
      complexes and integrate signals from cell surface receptors to the nucleus,
      modulating the specificity and selectivity of intracellular signal transduction.
      Grap2 is a newly identified adaptor protein specifically expressed in lymphoid
      tissues. This protein shares 40--50% sequence homology in the SH3 and the SH2
      domain with Grb2 and Grap. However, the Grap2 protein has a unique 120-amino acid
      glutamine- and proline-rich domain between the SH2 and C-terminal SH3 domains.
      The expression of Grap2 is highly restricted to lymphoid organs and T
      lymphocytes. In order to understand the role of this specific adaptor protein in
      immune cell signaling and activation, we searched for the Grap2 interacting
      protein in T lymphocytes. We found that Grap2 interacted with the hematopoietic
      progenitor kinase 1 (HPK1) in vitro and in Jurkat T cells. The interaction was
      mediated by the carboxyl-terminal SH3 domain of Grap2 with the second proline
      rich motif of HPK1. Coexpression of Grap2 with HPK1 not only increased the kinase
      activity of HPK1 in the cell, but also had an additive effect on HPK1 mediated
      JNK activation. Furthermore, over expression of Grap2 and HPK1 induced
      significant transcriptional activation of c-Jun in the JNK signaling pathway and
      IL-2 gene reporter activity in stimulated Jurkat T cells. Therefore, our data
      suggest that the hematopoietic specific proteins Grap2 and HPK1 form a signaling
      complex to mediate the c-Jun NH(2)-terminal kinase (JNK) signaling pathway in T
      cells.

PMID- 11313917
TI  - Repression of transcription of the p27(Kip1) cyclin-dependent kinase inhibitor
      gene by c-Myc.
AB  - Upon engagement of the B Cell Receptor (BCR) of WEHI 231 immature B cells, a drop
      in c-Myc expression is followed by activation of the cyclin-dependent kinase
      inhibitor (CKI) p27(Kip1), which induces growth arrest and apoptosis. Here, we
      report inverse patterns of p27 and c-Myc protein expression follow BCR
      engagement. We present evidence demonstrating, for the first time, that the
      p27(Kip1) gene is a target of transcriptional repression by c-Myc. Specifically,
      the changes in p27 protein levels correlated with changes in p27 mRNA levels, and
      gene transcription. Induction of p27 promoter activity followed BCR engagement of
      WEHI 231 cells, and this induction could be repressed upon co-transfection of a c
      Myc expression vector. Inhibition of the TATA-less p27 promoter by c-Myc was also
      observed in Jurkat T cells, vascular smooth muscle, and Hs578T breast cancer
      cells, extending the observation beyond immune cells. Consistent with a putative
      Inr element CCAGACC (where +1 is underlined) at the start site of transcription
      in the p27 promoter, deletion of Myc homology box II reduced the extent of
      repression. Furthermore, enhanced repression was observed upon transfection of
      the c-Myc 'super-repressor', with mutation of Phe115 to Leu. The sequences
      mediating transcriptional activity and c-Myc repression were mapped to bp -20 to
      +20 of the p27 gene. Finally, binding of Max was shown to facilitate c-Myc
      binding and repression of p27 promoter activity. Overall, these studies identify
      the p27 CKI gene as a new target whereby c-Myc can control cell proliferation,
      survival and neoplastic transformation.

PMID- 11313919
TI  - Regulation of estrogenic and nuclear factor kappa B functions by polyamines and
      their role in polyamine analog-induced apoptosis of breast cancer cells.
AB  - The natural polyamines -putrescine, spermidine, and spermine- are essential for
      cell growth and differentiation. Polyamines are involved in several gene
      regulatory functions, although their mechanism(s) of action has not been
      elucidated. We investigated the role of polyamines in the function of NF-kappa B
      and estrogen receptor-alpha (ER alpha), two transcription factors implicated in
      breast cancer cell proliferation and cell survival, using MCF-7 breast cancer
      cells. We found that spermine facilitated the binding of ER alpha and NF-kappa B
      to estrogen response element (ERE)- and NF-kappa B response element (NRE),
      respectively, and enhanced ER alpha-mediated transcriptional activation in
      transient transfection experiments. We also found that the association of the co
      regulatory protein CBP/p300 with ER alpha and NF-kappa B was increased by
      spermine treatment of MCF-7 cells. Spermine also increased the nuclear
      translocation of NF-kappa B compared to the control. In contrast, treatment of
      MCF-7 cells with polyamine analogs, BE-3-4-3 and BE-3-3-3, resulted in
      transcriptional inhibition of both ERE- and NRE-driven reporter plasmids. In
      addition, polyamine analogs inhibited the association of ER alpha and NF-kappa B
      with CBP/p300 and were unable to facilitate nuclear translocation of NF-kappa B.
      APO-BRDU assay demonstrated that polyamine analogs induced apoptosis, with a loss
      of the anti-apoptotic protein Bcl-2. These data show a gene regulatory function
      of polyamines involving transcriptional activation of ER alpha and NF-kappa B,
      potentially leading to the up-regulation of genes involved in breast cancer cell
      proliferation. Our results with BE-3-4-3 and BE-3-3-3 suggest that down
      regulation of ER alpha- and NF-kappa B-regulated genes is a possible mechanism
      for the action of polyamine analogs in inducing apoptosis of breast cancer cells.

PMID- 11313920
TI  - Serum induction of the fibroblast growth factor-binding protein (FGF-BP) is
      mediated through ERK and p38 MAP kinase activation and C/EBP-regulated
      transcription.
AB  - The fibroblast growth factor-binding protein (FGF-BP) modulates FGF activity
      through binding and release from the extracellular matrix. Consequently, the
      expression of FGF-BP in certain tumor types is a rate-limiting regulator of FGF
      mediated angiogenesis. FGF-BP is upregulated in squamous cell carcinoma by
      treatment with mitogens such as EGF or TPA. In this study, we investigated the
      regulation of FGF-BP gene expression by serum. Treatment of serum-starved ME-180
      cells with fetal bovine serum (FBS) resulted in a rapid increase in steady-state
      levels of FGF-BP mRNA and in the rate of FGF-BP gene transcription. Serum
      induction of FGF-BP mRNA was not mediated through EGF receptor activation but was
      dependent on PKC, as well as ERK kinase (MEK) and p38 MAP kinase activation.
      Promoter analysis showed that C/EBP is the main promoter element required for the
      serum response. Unlike EGF-activation of FGF-BP, transcriptional induction by
      serum is not significantly regulated through the AP-1 or E-box sites in the
      promoter. These results illustrate differences between the mechanism of induction
      in response to serum and EGF.

PMID- 11313921
TI  - c-Cbl facilitates fibronectin matrix production by v-Abl-transformed NIH3T3 cells
      via activation of small GTPases.
AB  - The protooncogenic protein c-Cbl has been shown to act as a multivalent adaptor
      and a negative regulator of protein tyrosine kinase-mediated signaling. Recent
      studies have implicated it in the regulation of cell adhesion-related events. We
      have previously shown that c-Cbl facilitates adhesion and spreading of v-Abl
      transformed fibroblasts, and that these effects are dependent on its tyrosine
      phosphorylation. However, the mechanisms mediating effects of c-Cbl on fibroblast
      adhesion remain poorly understood. In this study we demonstrate that the tyrosine
      phosphorylation-dependent effect of c-Cbl on adhesion of v-Abl-transformed
      fibroblasts is primarily mediated by an increase in fibronectin matrix deposition
      by these cells. This increase in fibronectin matrix deposition and, hence, in
      cell adhesion is dependent on cytoskeletal rearrangements induced by RhoA, Rac1
      and, possibly, Rap1 activation caused by c-Cbl. The observed activation of these
      GTPases is mediated by the recruitment of phosphatidylinositol-3' kinase, CrkL
      and Vav2 to the C-terminal tyrosine residues of c-Cbl. The results of this study
      also demonstrate that ubiquitination is essential for the observed effects of c
      Cbl on fibronectin matrix production and cell adhesion.

PMID- 11313922
TI  - Phosphorylation of the EWS IQ domain regulates transcriptional activity of the
      EWS/ATF1 and EWS/FLI1 fusion proteins.
AB  - Specific chromosomal translocations are commonly present in mesenchymal tumors
      and frequently involve genes encoding transcription factors. The combination of
      different domains from unrelated genes results in chimeric proteins believed to
      play a key role in the neoplastic process. The EWS/ATF1 and EWS/FLI1 fusion
      proteins associated with Clear Cell Sarcoma and Ewing's Sarcoma, respectively,
      were utilized to study the comparative effect of the EWS component on two
      different DNA binding partners. A potential regulatory site within the EWS IQ
      domain at serine266 was identified, and studies were performed to demonstrate
      that EWS is phosphorylated in cells and phosphorylation of serine266 regulates
      transcriptional activity. Mutational analysis showed that elimination of
      phosphorylation significantly reduced DNA binding activity by EMSA and reporter
      activation in luciferase assays, whereas phosphorylation mimicry resulted in a
      partial restoration to wild-type levels. Phosphorylation was also observed to
      mediate cellular compartmentalization. These studies confirm that IQ domain
      phosphorylation regulates the transcriptional activity of exogenous EWS/ATF1 and
      EWS/FLI1 and suggests that post-translational modifications may potentiate the
      neoplastic behavior of fusion proteins in general. Since the IQ domain is
      incorporated into only a subset of fusion transcripts, these findings may provide
      insight into the molecular mechanism underlying clinical heterogeneity observed
      in Ewing's sarcoma.

PMID- 11313923
TI  - Promoter methylation of DAP-kinase: association with advanced stage in non-small
      cell lung cancer.
AB  - Death associated protein (DAP)-kinase is a 16 kDa calmodulin-dependent
      serine/threonine kinase that carries a death domain at its C-terminus. DAP-kinase
      functions as a positive mediator of apoptosis that is induced by interferon
      gamma. Recent studies suggest that DAP-kinase is involved in tumor metastasis and
      that it can be inactivated by methylation of CpG islands in the promoter region
      of the gene in some human tumors. However, little is known about the factors that
      are associated with the occurrence of DAP-kinase promoter methylation. We
      investigated both the possible associations of tobacco carcinogen and asbestos
      exposure with DAP-kinase promoter methylation, and the demographic and clinical
      factors associated with DAP-kinase promoter methylation in non-small cell lung
      cancer (NSCLC). One hundred and eighty-five patients diagnosed with NSCLC
      undergoing surgical resection from June, 1992 through December, 1996 at
      Massachusetts General Hospital participated in this study. Methylation-Specific
      PCR (MSP), performed using fresh-frozen tissue, was used to determine the
      methylation status of the promoter region of the DAP-kinase gene. Forty-seven
      (25%) of 185 tumors showed DAP-kinase promoter methylation. There was a
      significant association between methylation and an advanced pathologic stage
      (P=0.003, Fisher's exact test). Methylation of the DAP-kinase promoter was also
      associated with an increase in tumor size (P=0.009, Fisher's exact test) and
      lymph node involvement (P=0.04). No association was found between promoter
      methylation of DAP-kinase and k-ras or p53 mutation. In addition there was no
      association with a history of exposure to tobacco or asbestos. Controlling for
      age, sex, and histology, the odds ratios describing the association of DAP-kinase
      hypermethylation with stage were 2.70 (1.13--6.45), 3.11 (1.37--7.08) and 7.77
      (1.21--50.03) in stages II, III and IV, respectively. Stage I cases with DAP
      kinase promoter methylation had worse overall survival, but with the small sample
      size and limited follow-up this did not reach statistical significance. Our
      findings suggest that methylation of the promoter region of the DAP-kinase gene
      is not associated with exposure to tobacco or asbestos. However, they strongly
      suggest that DAP-kinase may be important in the progression of non-small cell
      lung cancer from early to late stage disease.

PMID- 11313924
TI  - Cytokine response gene 8 (CR8) regulates the cell cycle G1-S phase transition and
      promotes cellular survival.
AB  - Cellular proliferation and survival are modulated by the expression of specific
      genes. Cytokine response gene 8 (CR8), which was originally cloned as an IL-2
      induced gene in human T lymphocytes, encodes a basic helix--loop--helix (bHLH)
      transcription factor. The CR8 gene product is highly conserved among human, mouse
      and rat, and contains sequence motifs that distinguish it from other bHLH
      families. The CR8 gene is ubiquitously expressed, and CR8 gene expression is
      induced by both growth-promoting as well as growth-inhibitory stimuli. As bHLH
      proteins have been found to regulate both the G1-S phase cell cycle transition,
      as well as cellular survival, the effects of CR8 on these processes were
      investigated. Ectopic CR8 expression in asynchronous U2OS cell cultures reduces
      the percentage of cells in the cell cycle S phase, and also slows the entry of G1
      synchronized cells into S phase. The prolonged G1 interval correlates with
      impaired elevation of cyclin E protein and prolonged p21 protein expression in
      G1. CR8 expression also protects U2OS cells from serum-withdrawal induced
      apoptosis. These results indicate that CR8 is an important modulator of both the
      G1-S phase cell cycle transition, and cellular survival.

PMID- 11313925
TI  - Constitutive c-Myb amino-terminal phosphorylation and DNA binding activity
      uncoupled during entry and passage through the cell cycle.
AB  - The c-myb gene encodes a transcription factor that is central to hematopoietic
      cell growth. Phosphorylation of c-Myb by casein kinase 2 (CK2) at serines 11 and
      12 has been variously implicated in the regulation of DNA binding. However, it is
      unclear when c-Myb phosphorylation at serines 11 and 12 occurs during the cell
      cycle and how this is regulated. We generated specific antisera that recognize
      phosphoserines 11 and 12 of c-Myb. C-Myb protein levels, extent of CK2
      phosphorylation and DNA binding were then monitored following mitogenic stimulus
      and passage through the cell cycle in normal peripheral T-cells and the T
      leukemia cell line CCRF-CEM. We found that endogenous c-Myb is constitutively
      phosphorylated at serines 11 and 12. The amount of phosphorylated c-Myb
      correlates with DNA binding activity in cycling CEM cells but not upon entry of T
      cells into the cell cycle. Exogenous expression of c-Myb with substitutions of
      serines 11 and 12 with glutamic acid or alanine had no effect on the
      transactivation of a c-Myb responsive reporter. These data strongly suggest that
      c-Myb is constitutively phosphorylated on serines 11 and 12 by CK2 or like
      activity and is not regulated during the cell cycle.

PMID- 11313926
TI  - Regulatory region of metastasis-inducing DNA is the binding site for T cell
      factor-4.
AB  - Small 1000 bp fragments of DNA derived from human malignant breast cancer cells
      have been isolated which, when transfected into a benign rat mammary cell line
      induce the production of osteopontin and thereby endow those cells with the
      capability to metastasize in syngeneic rats. Using transient transfections of an
      osteopontin promoter-reporter construct, we have now identified the active moiety
      in the metastasis-inducing DNA as the binding site for the T cell factor (Tcf)
      family of transcription factors and located Tcf-4, beta-catenin and E-cadherin in
      the relevant DNA complex in vitro. The regulatory effects of the metastasis
      inducing DNAs are therefore exerted, at least in part, by a CAAAG sequence which
      can sequester Tcf-4, thereby promoting transcription of the direct effector for
      metastasis in this system, osteopontin.

PMID- 11313927
TI  - Induction of the common fragile site FRA3B does not affect FHIT expression.
AB  - A long-standing issue concerns the extent to which fragile sites predispose to
      cancer-associated chromosomal rearrangements. The FHIT gene at chromosome 3p14.2
      spans the most common fragile site, FRA3B, in the human genome. Although the FHIT
      gene is altered in many human cancers, its status as a tumor suppressor gene has
      remained controversial, particularly since functional studies provided
      contradictory results. It had been suggested the FHIT alterations result from
      FRA3B induction promoted by the interference of carcinogens with DNA replication.
      Here we investigated the effect of FRA3B induction on FHIT expression. Common
      fragile sites were induced by treatment with aphidicolin and scored
      cytogenetically. FHIT transcription was analysed by RT--PCR and RNase protection
      analysis. Unexpectedly, FHIT transcription proceeded unchanged after fragile site
      induction. Aberrant FHIT transcripts lacking one or more exons were not observed.
      Moreover, Western blots revealed that the levels of FHIT prior to and following
      fragile site induction was unchanged, whereas p53 was found at elevated levels
      after induction. FRA3B induction thus has no direct effect on FHIT transcription
      and translation.

PMID- 11313928
TI  - Regulation of the G2/M transition by p53.
AB  - p53 protects mammals from neoplasia by inducing apoptosis, DNA repair and cell
      cycle arrest in response to a variety of stresses. p53-dependent arrest of cells
      in the G1 phase of the cell cycle is an important component of the cellular
      response to stress. Here we review recent evidence that implicates p53 in
      controlling entry into mitosis when cells enter G2 with damaged DNA or when they
      are arrested in S phase due to depletion of the substrates required for DNA
      synthesis. Part of the mechanism by which p53 blocks cells at the G2 checkpoint
      involves inhibition of Cdc2, the cyclin-dependent kinase required to enter
      mitosis. Cdc2 is inhibited simultaneously by three transcriptional targets of
      p53, Gadd45, p21, and 14-3-3 sigma. Binding of Cdc2 to Cyclin B1 is required for
      its activity, and repression of the cyclin B1 gene by p53 also contributes to
      blocking entry into mitosis. p53 also represses the cdc2 gene, to help ensure
      that cells do not escape the initial block. Genotoxic stress also activates p53
      independent pathways that inhibit Cdc2 activity, activation of the protein
      kinases Chk1 and Chk2 by the protein kinases Atm and Atr. Chk1 and Chk2 inhibit
      Cdc2 by inactivating Cdc25, the phosphatase that normally activates Cdc2. Chk1,
      Chk2, Atm and Atr also contribute to the activation of p53 in response to
      genotoxic stress and therefore play multiple roles. p53 induces transcription of
      the reprimo, B99, and mcg10 genes, all of which contribute to the arrest of cells
      in G2, but the mechanisms of cell cycle arrest by these genes is not known.
      Repression of the topoisomerase II gene by p53 helps to block entry into mitosis
      and strengthens the G2 arrest. In summary, multiple overlapping p53-dependent and
      p53-independent pathways regulate the G2/M transition in response to genotoxic
      stress.

PMID- 11313929
TI  - The small-GTPase RalA activates transcription of the urokinase plasminogen
      activator receptor (uPAR) gene via an AP1-dependent mechanism.
AB  - The urokinase plasminogen activator receptor (uPAR) focuses extracellular
      protease activity to the cell surface, modulates cell adhesion and activates
      intracellular signal transduction pathways. In a range of cancers uPAR expression
      often has a negative correlation with prognosis. Here we show that uPAR
      transcription is stimulated by V12 H-Ras, the effector loop mutant V12 H-Ras G37
      and constitutively-active RalA 72L. RalA-dependent transcription required the
      presence of the ATF2-like AP1-site at -70 bp and the c-Jun binding motif at -184
      bp in the uPAR promoter. Consistent with this, both Gal4-c-Jun- and Gal4-ATF2
      fusion proteins were activated by RalA signalling through phosphorylation of
      their activation domains at Ser63 and Ser73 of c-Jun or Thr69 and Thr71 of ATF2.
      A transdominant inhibitory mutant of c-Jun N-terminal kinase (JNK) failed to
      inhibit uPAR transcription demonstrating that JNK activation is not a
      prerequisite for RalA-dependent uPAR transcription. A dominant negative inhibitor
      of c-Src effectively inhibited RalA-dependent uPAR transcription identifying it
      as a downstream effector in the RalA signalling pathway. These data provide
      evidence for the existence of a novel signalling pathway that links RalA to the
      activation of uPAR transcription via a c-Src intermediate and activation of AP1.

PMID- 11313930
TI  - Induction of hepatocyte proliferation and liver hyperplasia by the targeted
      expression of cyclin E and skp2.
AB  - Cells in culture become competent to replicate in the absence of growth factor
      after progressing beyond the late G1 restriction point, suggesting that a set of
      genes expressed during G1 phase is sufficient to trigger completion of the cell
      cycle. However, this has not been demonstrated in an in vivo system. In this
      study, we examined whether transfection of genes associated with the G1/S
      transition could trigger hepatocyte replication. Co-transfection of cyclin E and
      skp2 synergistically promoted cell cycle progression in cultured primary
      hepatocytes in the absence of mitogen or in the presence of growth inhibitors.
      Furthermore, transfection of hepatocytes in vivo with cyclin E and skp2 promoted
      abundant hepatocyte replication and hyperplasia of the liver. These studies
      confirm that transfection with a small number of genes can trigger proliferation
      of quiescent hepatocytes in vivo, and suggest that therapies to enhance liver
      regeneration by targeting cell cycle control genes may be feasible.

PMID- 11313931
TI  - Cdk10, a Cdc2-related kinase, associates with the Ets2 transcription factor and
      modulates its transactivation activity.
AB  - Cdk10 is a Cdc2-related kinase that may play a role in regulating the G2/M phase
      of the cell cycle. However little is known about the proteins that interact with
      this putative kinase and contribute to its function in the cell. We report in
      this study that Cdk10 interacts with the N-terminus of the Ets2 transcription
      factor, which contains the highly conserved Pointed domain and transactivation
      domain. The Pointed domain has been implicated in protein-protein interactions
      and we find that Ets2 requires an intact Pointed domain to bind Cdk10. The
      Pointed domain of Ets1 is highly similar to Ets2, however Cdk10 does not
      recognize Ets1 in a two-hybrid assay thereby demonstrating significant binding
      specificity on the part of Cdk10. We find that Cdk10 binds full length Ets2 in
      vitro and in vivo and inhibits Ets2 transactivation in mammalian cells.

PMID- 11313932
TI  - Localization of human Cdc25C is regulated both by nuclear export and 14-3-3
      protein binding.
AB  - Entry into mitosis requires activation of the Cdc2 protein kinase by the Cdc25C
      protein phosphatase. The interactions between Cdc2 and Cdc25C are negatively
      regulated throughout interphase and in response to G2 checkpoint activation. This
      is accomplished in part by maintaining the Cdc25 phosphatase in a phosphorylated
      form that binds 14-3-3 proteins. Here we report that 14-3-3 binding regulates the
      intracellular trafficking of Cdc25C. Although primarily cytoplasmic, Cdc25C
      accumulated in the nuclei of leptomycin B (LMB)-treated cells, indicating that
      Cdc25C is actively exported out of the nucleus. A mutant of Cdc25C that is unable
      to bind 14-3-3 was partially nuclear in the absence of LMB and its nuclear
      accumulation was greatly enhanced by LMB-treatment. A nuclear export signal (NES)
      was identified within the amino terminus of Cdc25C. Although mutation of the NES
      did not effect 14-3-3 binding, it did cause nuclear accumulation of Cdc25C. These
      results demonstrate that 14-3-3 binding is dispensable for the nuclear export of
      Cdc25C. However, complete nuclear accumulation of Cdc25C required loss of both
      NES function and 14-3-3 binding and this was accomplished both pharmacologically
      and by mutation. These findings suggest that the nuclear export of Cdc25C is
      mediated by an intrinsic NES and that 14-3-3 binding negatively regulates nuclear
      import.

PMID- 11313933
TI  - Activation of the Fas pathway independently of Fas ligand during apoptosis
      induced by camptothecin in p53 mutant human colon carcinoma cells.
AB  - The present study explored the role of the cell surface receptor Fas (CD95/APO-1)
      in apoptosis induced by camptothecin (CPT) in the HT29 colon carcinoma cell line.
      CPT-induced apoptosis was associated with high molecular weight DNA fragmentation
      as measured by filter elution. This fragmentation was inhibited by the caspase
      inhibitor, z-VAD-fmk and by cycloheximide, which also prevented proteolytic
      activation of caspase-3 and poly(ADP-ribose)polymerase cleavage. Under such
      conditions, Fas, Fas ligand, Bax, and p21 expression were increased and Fas
      recruited the FADD adaptor. Fas expression increase was blocked by cycloheximide
      but not by z-VAD-fmk, consistent with caspase activation downstream from Fas.
      Treatment of HT29 cells with FasL or with the CH-11 agonistic anti-Fas antibody
      potentiated the apoptotic response of cells treated with CPT. The anti-Fas
      blocking antibody ZB4 and the Fas-ligand inhibitor failed to protect HT29 cells
      from CPT-induced apoptosis. Such a protection was obtained by transient
      expression of constructs encoding a dominant-negative mutant of FADD, FADD in an
      antisense orientation and E8 or MC159 viral proteins that inhibit Fas-induced
      apoptosis at the level of FADD and procaspase-8, respectively. Together, these
      data show that topoisomerase I-mediated DNA damage-induced apoptosis involves
      activation of the Fas pathway without detectable Fas-ligand requirement in CPT
      treated cells.

PMID- 11313934
TI  - Synergistic growth inhibition of prostate cancer cells by 1 alpha,25
      Dihydroxyvitamin D(3) and its 19-nor-hexafluoride analogs in combination with
      either sodium butyrate or trichostatin A.
AB  - Prostate cancer is a major cause of male cancer death. In vitro and in vivo data
      support a role for 1 alpha,25 Dihydroxyvitamin D(3) (1 alpha,25(OH)(2)D(3)) in
      regulating the growth and differentiation of the normal prostate gland yet
      prostate cancer cells appear significantly less sensitive to this action. Vitamin
      D(3) receptor (VDR) content or mutational status do not correlate clearly with
      the antiproliferative effects of 1 alpha,25(OH)(2)D(3) and therefore it is
      unclear why prostate cancer cell lines are significantly less sensitive to this
      action. We hypothesized that the antiproliferative responses of prostate cancer
      cells to 1 alpha,25(OH)(2)D(3) are suppressed by a process involving histone
      deacetylation. Sodium butyrate (NaB) and trichostatin A (TSA) are inhibitors of
      histone deacetylase (HDAC) activity. Low doses of NaB or TSA (300 microM and 15
      nM respectively), which alone were relatively inactive, synergized with 1
      alpha,25(OH)(2)D(3) in liquid and semi-solid agar to inhibit the growth of LNCaP,
      PC-3 and DU-145 prostate cancer cells. Still greater synergy was observed between
      vitamin D(3) hexafluoride analogs and either NaB or TSA. The mechanism appeared
      to involve neither the cyclin-dependent kinase inhibitor, p21((waf1/cip1)) nor
      cell cycle arrest, but rather induction of apoptosis. These data suggest that
      cells dysregulate the normal pro-apoptotic signals of 1 alpha,25(OH)(2)D(3)
      during prostate cancer development by a mechanism involving histone
      deacetylation. Combination therapy with potent vitamin D(3) analogs and
      clinically approved HDAC inhibitors may overcome this lesion and improve the
      treatment of both androgen-dependent and independent prostate cancer.

PMID- 11313935
TI  - BCR gene expression blocks Bcr-Abl induced pathogenicity in a mouse model.
AB  - It is well accepted that the Bcr-Abl oncoprotein encoded by the Philadelphia
      chromosome is responsible for causing chronic myelogenous leukemia (CML). We have
      previously demonstrated that expression of Bcr interferes with the oncogenic
      effects of Bcr-Abl. To examine the effects of increased Bcr expression on Bcr-Abl
      oncogenic effects in a more physiological system, we tested the leukemogenic
      potential of a clone of K562 cells (K6 K562) containing an inducible BCR gene in
      NOD/scid mice. In this clone, the BCR gene was placed under the control of a
      tetracycline (Tet) repression system with a cytomegalovirus (CMV) promoter.
      Induction of exogenous Bcr protein by removal of Tet from the culture medium
      caused a dramatic increase in Bcr serine kinase activity, yielding predominantly
      phosphoserine Bcr, despite the presence of Bcr-Abl in the kinase reaction
      mixture. Prior to induction, the endogenous Bcr was predominantly in the
      phosphotyrosine form because of phosphorylation by Bcr-Abl, which we previously
      have shown suppresses Bcr serine/threonine kinase activity. Injection of K6 K562
      cells into NOD/scid mice under conditions where BCR expression was suppressed
      resulted in death or terminal illness in 100% of the mice within 35 days after
      injection. These mice had a severe wasting syndrome characterized by atrophy of
      bone marrow hematopoiesis, and/or neoplasia of liver, bone marrow and spleen.
      Neoplastic spleens from these mice usually contained b3a2 Bcr-Abl transcripts. In
      contrast, induction of BCR expression at the time of injection allowed 80%
      survival; these healthy mice had no detectable microscopic lesions in blood
      forming organs. This difference in survival was significant with P<0.0001. Of
      interest, mice that were fed Tet for 19 days to initiate the disease syndrome and
      then released from the BCR transcriptional block had a significantly better
      survival pattern than mice exposed to Tet throughout the entire period. Moreover,
      30% of these mice (three mice) survived through day 50. We conclude from these
      findings that BCR gene expression strongly inhibits the oncogenic effects of Bcr
      Abl in NOD/scid mice, yielding healthy mice in most cases.

PMID- 11313936
TI  - The p107 tumor suppressor induces stable E2F DNA binding to repress target
      promoters.
AB  - E2F transcription factors are key players in the regulation of proliferation,
      apoptosis, and differentiation in mammalian cells. E2Fs are negatively regulated
      by members of the retinoblastoma protein family, Rb, p107 and p130. During
      adenovirus infection, viral proteins are expressed that displace Rb family
      members from E2Fs and recruit E2F complexes to viral and cellular promoter
      regions. This recruitment of E2F involves the induction of stable E2F binding to
      inverted E2F binding sites in the Ad E2a and cellular E2F-1 promoters and induces
      both viral and cellular gene expression. The cellular p107 tumor suppressor also
      displays such regulation of E2F DNA binding activity. p107 induces stable E2F
      4/DP binding to inverted E2F binding sites in the Ad E2a and cellular E2F-1
      promoters. The induction of E2F DNA binding by p107 minimally requires the
      sequences in p107 that mediate E2F interaction. The related tumor suppressor,
      p130, also effects this function. p107 levels increase substantially as cells
      progress through S phase. p107 induction of E2F DNA binding was observed
      primarily in S phase cells coincident with the increase in p107 protein levels.
      The results of promoter activity assays directly correlate the induction of E2F
      DNA binding by p107 with effective transcriptional repression. These results
      support a model in which p107 and p130 induce the stable binding of E2F complexes
      to promoters that drive expression of critical regulatory proteins such as E2F-1.
      Since p107 and p130 bind histone deacetylase complexes (HDACs) which repress
      promoter activity, p107-E2F and p130-E2F would stably recruit repressor complexes
      to effect efficient promoter repression.

PMID- 11313937
TI  - Alterations in protein phosphatase 2A subunit interaction in human carcinomas of
      the lung and colon with mutations in the A beta subunit gene.
AB  - Protein phosphatase 2A (PP2A) consists of three subunits, A, B and C. The A and B
      subunits have regulatory functions while C is the catalytic subunit. PP2A core
      enzyme is composed of subunits A and C, and the holoenzyme of subunits A, B and
      C. All subunits exist as multiple isoforms or splice variants. The A subunit
      exists as two isoforms, A alpha and A beta. Here we report about the properties
      of eight A beta mutants, which were found in human lung and colon cancer. These
      mutants were reconstructed by site-directed mutagenesis and assayed for their
      ability to bind B and C subunits. Two mutants showed decreased binding of PR72, a
      member of the B" family of B subunits, but normal C subunit binding; two mutants
      exhibited decreased binding of the C subunit and of B"/PR72; and one mutant
      showed increased binding of both the C subunit and B"/PR72. Of three mutants that
      behaved like the wild-type A beta subunit, one is a polymorphic variant and
      another one is altered outside the binding region for B and C subunits.
      Importantly, we also found that the wild-type A alpha and A beta isoforms,
      although 85% identical, are remarkably different in their ability to bind B and C
      subunits. Our findings may have important implications in regard to the role of
      PP2A as a tumor suppressor.

PMID- 11313938
TI  - Activation of the I kappa B alpha kinase (IKK) complex by double-stranded RNA
      binding defective and catalytic inactive mutants of the interferon-inducible
      protein kinase PKR.
AB  - The interferon (IFN)-inducible double stranded (ds) RNA-activated protein kinase
      PKR plays an important role in protein synthesis by modulating the
      phosphorylation of the alpha-subunit of eukaryotic initiation fact 2 (eIF-2
      alpha). In addition to translational control, PKR has been implicated in several
      signaling pathways leading to gene transcription. For example, PKR induces I
      kappa B alpha kinase (IKK) activity and I kappa B alpha phosphorylation leading
      to the induction of NF-kappa B-mediated gene transcription. Recent findings
      suggested that NF-kappa B activation by PKR does not require the catalytic
      activity of the kinase. Here, we provide novel evidence that induction of IKK and
      NF-kappa B activities proceeds independently of the dsRNA-binding properties of
      PKR and also verify the kinase-free role of PKR in this process. We also show
      that the effects of PKR mutants on IKK and NF-kappa B activation are independent
      of cell transformation but are dependent on the amount of the mutant PKR proteins
      expressed in cells. These data strongly support an indirect role of PKR in I
      kappa B alpha phosphorylation by modulating IKK activity through pathways that do
      not utilize the enzymatic and dsRNA-binding properties of PKR.

PMID- 11313939
TI  - Fibroblast growth factor and insulin-like growth factor differentially modulate
      the apoptosis and G1 arrest induced by anti-epidermal growth factor receptor
      monoclonal antibody.
AB  - DiFi human colon carcinoma cells are stimulated by the transforming growth factor
      alpha (TGF-alpha)/epidermal growth factor (EGF) receptor autocrine loop. Exposure
      of DiFi cells to monoclonal antibody (mAb) 225, which blocks ligand-induced
      activation of the EGF receptor, induces G1 arrest and subsequent cell death via
      apoptosis. We investigated the signal pathways by which basic fibroblast growth
      factor (bFGF) and insulin-like growth factor-1 (IGF-1) modulate mAb 225-induced
      G1 arrest and apoptosis in DiFi cells. Both bFGF and IGF-1 activated the mitogen
      activated protein kinase (MAPK) kinase (MEK) pathway in DiFi cells. Additionally,
      IGF-1 activated the phosphoinositide 3-kinase (PI-3K)/Akt pathway. Both bFGF and
      IGF-1 inhibited mAb 225-induced apoptosis; however, bFGF provided sustained
      protection against apoptosis, while the protection by IGF-1 was only temporary.
      Also, bFGF reversed the mAb 225-induced increase in the p27(Kip1) level,
      inhibition of cyclin-dependent kinase-2 (CDK-2) activity, dephosphorylation of
      the retinoblastoma (Rb) protein and the resultant G1 arrest of the cells. In
      contrast, IGF-1 did not reverse such effects by mAb 225. The prevention of mAb
      225-induced G1 arrest and apoptosis in DiFi cells by bFGF was sensitive to the
      MEK/MAPK inhibitor PD98059 but not to the PI-3K inhibitor LY294002. In contrast,
      inhibition of apoptosis by IGF-1 in DiFi cells was sensitive only to LY294002 and
      not to PD98059. These results further our understanding of how mAb 225 induces
      apoptosis in DiFi cells.

PMID- 11313940
TI  - A role for mismatch repair in control of DNA ploidy following DNA damage.
AB  - Many reports have shown a link between mismatch repair (MMR) deficiency and loss
      of normal cell cycle control, particularly loss of G2 arrest. However almost all
      of these studies utilized transformed cell lines, and thus the involvement of
      other genes in this phenotype cannot be excluded. We have examined the effects of
      cisplatin treatment on primary embryo fibroblasts (MEFs) derived from mice in
      which the MMR gene Msh2 had been inactivated (Msh2(-/-)). This analysis
      determined that both primary Msh2(-/-) and wild type (WT) fibroblasts exhibited
      an essentially identical G2 arrest following cisplatin treatment. Similarly, we
      observed a cisplatin-induced G2 arrest in immortalized MMR deficient (Mlh1(-/-)
      and Pms2(-/-)) and WT MEFs. p53 deficient primary MEFs (p53(-/-)) exhibited both
      a clear G2 arrest and an increase in cells with a DNA content of 8N in response
      to cisplatin. When the Msh2 and p53 defects were combined (p53(-/-)/Msh2(-/-))
      the G2 arrest was essentially identical to the p53(-/-) fibroblasts. However, the
      p53(-/-)/Msh2(-/-) fibroblasts demonstrated a further increase in cells with an
      8N DNA content, above that seen in the p53(-/-) fibroblasts. These results
      suggest that loss of MMR on its own is not enough to overcome G2 arrest following
      exposure to cisplatin but does play a role in preventing polyploidization, or
      aberrant DNA reduplication, in the absence of functional p53.

PMID- 11313941
TI  - Irradiation of mitochondria initiates apoptosis in a cell free system.
AB  - The ability to modulate the sensitivity of mammalian cells to ionizing radiation
      (IR) (e.g. using chemotherapeutics) is dependent on our understanding of the
      primary target and biochemical pathway that leads to IR-induced apoptosis. We
      demonstrate using a cell free assay that irradiation of mitochondria is a primary
      event that initiates IR-induced apoptosis. IR results in loss of mitochondrial
      membrane potential, opening of the permeability transition pore (PTP) and the
      release of cytochrome c (cyto c). Apaf-1 and ATP were required to initiate
      apoptosis upon release of cyto c from mitochondria. The importance of
      mitochondrial events in the initiation of IR-induced apoptosis was also supported
      by the observation that inhibition of caspase-9 by the over-expression of
      dominant negative mutants resulted in the inhibition of IR-induced apoptosis. In
      contrast, inhibition of caspase-8 had only a minor impact on IR-induced
      apoptosis. Over-expression of Bcl-X(L) inhibited the initiation of IR-induced
      apoptosis due to its ability to prevent the loss of mitochondrial membrane
      potential, PTP opening and cytochrome c release. In a cell free assay for
      apoptosis, mitochondria as well as cytosol derived from Bcl-X(L) over-expressing
      cells were less efficient at supporting apoptosis in response to IR suggesting
      multiple roles for Bcl-X(L) in the regulation of apoptosis.

PMID- 11313942
TI  - PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is
      associated with pre-mRNA splicing factors.
AB  - In papillary renal cell carcinomas the TFE3 transcription factor becomes fused to
      the PSF and NonO pre-mRNA splicing factors and most commonly to a protein of
      unknown function designated PRCC. In this study we have examined the ability of
      the resulting PRCC-TFE3 and NonO-TFE3 fusions to activate transcription from the
      plasminogen activator inhibitor-1 (PAI-1) promoter. The results show that only
      fusion to PRCC enhanced transcriptional activation, indicating that the ability
      to enhance the level of transcription from endogenous TFE3 promoters is not a
      consistent feature of TFE3 fusions. In investigations of the normal function of
      PRCC we observed that PRCC expressed as a green fluorescent fusion protein
      colocalizes within the nucleus with Sm pre-mRNA splicing factors. It was also
      found that endogenous PRCC is coimmunoprecipitated by antibodies that recognize a
      variety of pre-mRNA splicing factors including SC35, PRL1 and CDC5. Association
      with the cellular splicing machinery is therefore, a common feature of the
      proteins that become fused to TFE3 in papillary renal cell carcinomas.

PMID- 11313943
TI  - Expression of a down-regulated target, SSeCKS, reverses v-Jun-induced
      transformation of 10T1/2 murine fibroblasts.
AB  - Line 10T1/2 mouse fibroblast overexpressing the v-Jun oncoprotein were
      morphologically altered, grew into multilayered foci in culture and formed
      colonies when suspended in agar. The growth rate of the v-Jun-transformed 10T1/2
      cells was not changed significantly from that of the untransformed parental
      cells, but the saturation density of the transformed cultures exceeded that of
      normal controls by a factor of 2. mRNA extracted from v-Jun-transformed 10T1/2
      cells was analysed for differential gene expression with DNA micro-array
      technology. One of the targets downregulated by v-Jun was identified as SSeCKS
      (Src-suppressed C kinase substrate). Re-expression of SSeCKS in v-Jun-transformed
      fibroblasts reversed the transformed phenotype of the cells. Their ability to
      form foci was reduced to background levels, the number and size of agar colonies
      was lowered by a factor of 10 and the saturation density was significantly
      diminished. However, expression of SSeCKS had little effect on the morphology of
      v-Jun-transformed 10T1/2 cells. These data suggest that the SSeCKS protein has
      growth-attenuating properties. Down-regulation of SSeCKS may be essential for Jun
      induced transformation.

PMID- 11313944
TI  - Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is
      independent of p53.
AB  - The anti-cancer agent paclitaxel (Taxol) stabilizes microtubules leading to G2/M
      cell cycle arrest and apoptotic cell death. In order to analyse the molecular
      mechanisms of Taxol-induced cytotoxicity, we studied the involvement of mitogen
      activated protein kinases (MAPK) ERK and p38 as well as the p53 pathways in Taxol
      induced apoptosis. The human breast carcinoma cell line MCF7 and its derivatives,
      MCF7/HER-2 and MDD2, were used in the study. We found that Taxol treatment
      strongly activated ERK, p38 MAP kinase and p53 in MAP kinase MCF7 cells prior to
      apoptosis. PD98059 or SB203580, specific inhibitors of ERK and p38 kinase
      activities, significantly decreased apoptosis, leaving the surviving cells
      arrested in G2/M. These inhibitors did not significantly affect Taxol-induced
      alterations in the cell cycle regulatory proteins Rb, p53, p21/Waf1 and Cdk-2. In
      addition, inactivation of p53 did not affect cellular sensitivity to Taxol
      killing. However, cells with inactivated p53, unlike cells harboring wild type
      p53, failed to arrest in G2/M after treatment with Taxol and continued to divide
      or go into apoptosis. Our data show that both ERK and p38 MAP kinase cascades are
      essential for apoptotic response to Taxol-induced cellular killing and are
      independent of p53 activity. However, p53 may serve as a survival factor in
      breast carcinoma cells treated with Taxol by blocking cells in G2/M phase of the
      cell cycle.

PMID- 11313945
TI  - Gab1 phosphorylation: a novel mechanism for negative regulation of HGF receptor
      signaling.
AB  - Signal transduction by HGF receptor, the tyrosine kinase encoded by the MET
      oncogene, switches on a genetic program called 'invasive growth' inducing
      epithelial cell dissociation, migration, growth, and ultimately leading to
      differentiation into branched tubular structures. Sustained tyrosine
      phosphorylation of the downstream adaptor protein Gab1 is required for the HGF
      response. Here we show that serine/threonine phosphorylation of Gab1 provides a
      control mechanism for negative regulation. Treatment with okadaic acid, a potent
      inhibitor of the serine/threonine protein phosphatases PP1 and PP2A, was followed
      by activation of a number of serine/threonine kinases, hyper-phosphorylation in
      serine and threonine of Gab1 and severe inhibition of the HGF-induced biological
      responses. Under these conditions, Gab1 was found to be concomitantly hypo
      phosphorylated in tyrosine, and thus endowed with reduced ability to recruit SH2
      containing signal transducers such as PI3 kinase. Among the serine-threonine
      kinases activated by PP1 and PP2A inhibition, we found that PKC-alpha and PKC
      beta1 are required for negative regulation of Gab1. These data provide a novel
      negative mechanism for the HGF receptor signaling pathways and highlight a
      potentially useful target for inhibitors of invasive growth.

PMID- 11313946
TI  - A novel potential effector of M-Ras and p21 Ras negatively regulates p21 Ras
      mediated gene induction and cell growth.
AB  - Here, we report the identification and characterization of a new member of the
      RalGDS-family, which is widely expressed and interacts strongly and selectively
      with the GTP-bound forms of M-Ras and p21 Ras. This Ras pathway modulator (RPM),
      also termed RGL3, exhibited Ras-binding and catalytic domains typical of the
      RalGDS-family of guanine nucleotide exchange factors, and was most similar to Rlf
      (RalGDS-like factor), but was distinguished by a unique proline-rich region with
      multiple candidate SH3-domain binding sites. RPM/RGL3 resembled AF-6 and Nore1 in
      interacting strongly with constitutively active M-Ras and p21 Ras. In contrast to
      Rlf, transiently expressed RPM/RGL3 did not activate an Elk-1-inducible reporter
      gene alone or in combination with activated p21 Ras, but strongly inhibited
      induction of this reporter gene by co-expression of activated H-Ras or MEKK-1.
      This inhibitory effect was independent of the Ras binding domain and required a
      second signal provided by p21 Ras or MEKK-1, but not Raf-1 or M-Ras. Expression
      of RPM/RGL3 also strongly inhibited cell growth of fibroblasts transformed by an
      activated Src Y527F. Thus, RPM/RGL3 is a novel potential effector of both p21 Ras
      and M-Ras with the novel function of negatively regulating Elk-1-dependent gene
      induction downstream of p21 Ras or MEKK-1.

PMID- 11313947
TI  - Overexpression of interleukin-6 in human basal cell carcinoma cell lines
      increases anti-apoptotic activity and tumorigenic potency.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the
      diverse functions of cells such as acute phase responses and inflammation.
      Excessive or insufficient production of IL-6 may contribute to certain diseases
      of the skin. The aim of this study was to investigate the possible role of IL-6
      in the tumorigenesis of basal cell carcinoma (BCC). Initially, we transfected IL
      6 expression vector, under the control of a CMV promoter, into human BCC cells
      and successfully obtained IL-6-overexpressing clones (BCC/IL-6-c1 and BCC/IL-6
      c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using (3)H-thymidine
      pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much
      higher DNA synthesis rate than the neo control or parental BCC cells. We also
      detected a greater abundance of IL-6-expressing cell colonies formed in soft agar
      than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector
      control cells, were resistant to UV and photodynamic therapy (PDT)-induced
      apoptosis, as confirmed using DNA fragmentation and morphologic change analyses.
      Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was
      specifically up-regulated IL-6 transfectants but not in the control cells.
      Transient transfection of IL-6 transfectants with antisense mcl-1 greatly
      enhanced their apoptosis frequency by UV treatment. In tumorigenesis assay, IL-6
      transfected clones formed tumors in nude mice more rapidly than the control
      cells. These tumors appeared to be highly vascularized using pathological
      examination. Supportive of this finding, we found that IL-6 transfected cells
      expressed elevated levels of two angiogenic factors, cyclooxygenase (Cox)-2 and
      vascular endothelial growth factor (VEGF). These results suggest that
      overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both
      suppressing apoptosis and actively promoting angiogenesis.

PMID- 11313948
TI  - The insulin receptor substrate (IRS)-1 recruits phosphatidylinositol 3-kinase to
      Ret: evidence for a competition between Shc and IRS-1 for the binding to Ret.
AB  - Tyrosine 1062 of Ret, which represents an intracytoplasmic docking site for
      multiple signaling molecules, is essential for Ret-mediated activation of
      phosphatidylinositol 3-Kinase (PI3-K). PI3-K, in turn, has been implicated in
      inducing cell survival and neoplastic transformation mediated by Ret. We have
      examined the mechanisms by which Ret stimulates PI3-K. Here we show that the
      Insulin Receptor Substrate-1 (IRS-1) is tyrosine phosphorylated and associated
      with the p85 regulatory subunit of PI3-K in response to Ret activation. IRS-1
      coimmunoprecipitates with Ret and co-expression of IRS-1 results in the
      potentiation of Ret-mediated activation of Akt(PKB), a bona fide effector of PI3
      K. The association with the PTB domain of IRS-1 depends on the phosphorylation of
      tyrosine 1062 of Ret. The deletion of asparagine 1059 (delN1059) and the
      substitution of leucine 1061 (L1061P), two Ret mutations identified in families
      affected by congenital megacolon (Hirschsprung's disease), impair the binding of
      IRS-1 to Ret as well as Ret-mediated Akt(PKB) stimulation. Finally, we show that
      Shc, which was previously identified as another ligand of Y1062 of Ret, competes
      with IRS-1 for the binding to Ret pY1062. All together, these findings suggest
      that IRS-1 is a component of the signaling pathway which leads to Ret-mediated
      PI3-K activation, a pathway which can be targeted by Hirschsprung-associated Ret
      mutations. The alternative binding of Shc and IRS-1 to Ret pY1062 can be a system
      to modulate the activation of different intracellular signaling pathways and to
      elicit different biological responses following Ret activation.

PMID- 11313949
TI  - The CEACAM1-L Ser503 residue is crucial for inhibition of colon cancer cell
      tumorigenicity.
AB  - CEACAM1 (also known as biliary glycoprotein, C-CAM or CD66a) is a cell adhesion
      molecule of the immunoglobulin family behaving as a tumor inhibitory protein in
      colon, prostate, liver, endometrial and breast cancers. Inhibition of tumor
      development is dependent upon the presence of the long 71-73 amino acid
      cytoplasmic domain of the CEACAM1 protein (CEACAM1-L). We have recently defined a
      number of cis-acting motifs within the long cytoplasmic domain participating in
      tumor cell growth inhibition. These are Tyr488, corresponding to an
      Immunoreceptor Tyrosine-based Inhibition Motif, as well as the three terminal
      lysine residues of the protein. In this study, we provide evidence that treatment
      with phorbol esters leads to increased phosphorylation of in vivo (32)P-labeled
      CEACAM1-L in mouse CT51 carcinoma cells, in the mouse 1MEA 7R.1 liver carcinoma
      cells and in 293 human embryonic kidney cells transfected with the Ceacam1-L
      cDNA. Basal level Ser phosphorylation was abrogated by treatment with the
      staurosporine inhibitor, but not by the protein kinase C-specific inhibitor
      calphostin C or other inhibitors such as H7 or sphingosine. Specific inhibitors
      of protein kinase A or calmodulin kinase had only minimal effects on the levels
      of basal or PMA-induced Ser phosphorylation. Furthermore, PMA treatment of the
      CT51 cells induced cell spreading and cellular relocalization of the CEACAM1-L
      protein. Since Ser503 has been described as a PMA-induced phosphorylation site in
      other cell systems, we investigated whether Ser503 was involved in these
      responses in mouse intestinal cells. No differences were noticed in the basal or
      the PMA-induced phosphorylation levels, kinase inhibitor sensitivity or the PMA
      induced relocalization of the protein between the wild-type and the Ser503Ala
      mutant CEACAM1-L. However, we provide evidence that Ser503 participates in
      CEACAM1-L-mediated tumor inhibition as its mutation to an Ala led to in vivo
      tumor development, contrary to the tumor inhibitory phenotype observed with the
      wild-type CEACAM1-L protein.

PMID- 11313950
TI  - The chicken Pdcd4 gene is regulated by v-Myb.
AB  - The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is
      responsible for the ability of avian myeloblastosis virus (AMV) to transform
      myelomonocytic cells. v-Myb is thought to disrupt the differentiation of
      myelomonocytic cells by affecting the expression of specific target genes. To
      identify such genes we have analysed the gene expression in a myelomonocytic
      chicken cell line that carries an estrogen inducible version of v-Myb by
      differential display. Here we describe the identification of the chicken homolog
      of the mouse Pdcd4 gene as a novel v-Myb target gene. Pdcd4 is also known as MA
      3, TIS and H731 and has recently been shown to suppress the transformation of
      epidermal cells by tumor promoters. Our results provide the first evidence that v
      Myb directly regulates the expression of a potential tumor suppressor gene.

PMID- 11313951
TI  - Negative regulation of bcl-2 expression by p53 in hematopoietic cells.
AB  - The p53 protein activates promoters containing p53 binding sites, and it
      represses other promoters. We examined the effect of p53 on bcl-2 expression in
      both the DHL-4 B cell line and the K562 erythroleukemia line. Transient
      transfection analyses revealed that wild-type p53 repressed the bcl-2 full-length
      promoter. The region of the bcl-2 promoter that was responsive to p53 was mapped
      to the bcl-2 P2 minimal promoter region, and we showed that p53 and the TATA
      binding protein bound to the bcl-2 TATA sequence. The TATA binding protein, p53,
      histone deacetylase-1 and mSin3a could be co-immunoprecipitated from K562 cell
      nuclear extract. The TATA binding protein and mSin3a could be recovered in a
      complex at the bcl-2 promoter TATA sequence, however, the formation of this
      complex was not dependent on the presence of p53. Treatment of K562 cells with
      the histone deacetylase inhibitor, trichostatin A, resulted in an increase in bcl
      2 promoter activity whether p53 was present or not. Therefore, we demonstrated
      that p53 and the histone deacetylases repress the bcl-2 promoter independently.
      Similar results were obtained when endogenous bcl-2 mRNA or protein levels were
      measured in response to either p53 or trichostatin A, and p53 expression resulted
      in enhanced apoptosis. RNase protection assays demonstrated that transcription
      from the endogenous 3' bcl-2 promoter was decreased by p53. The regions of p53
      that were required for repression of the bcl-2 promoter were defined. We conclude
      that the TATA sequence in the bcl-2 P2 minimal promoter is the target for
      repression by p53, and that the interaction between p53 and TBP is most likely
      responsible for the repression. Mutation of p53 may play a role in the up
      regulation of bcl-2 expression in some B cell lymphomas.

PMID- 11313952
TI  - Insulin and IGF-1 stimulate the beta-catenin pathway through two signalling
      cascades involving GSK-3beta inhibition and Ras activation.
AB  - We examined the interplay between the insulin/IGF-1- and beta-catenin-regulated
      pathways, both of which are suspected to play a role in hepatocarcinogenesis.
      Insulin and IGF-1 stimulated the transcription of a Lef/Tcf-dependent luciferase
      reporter gene by 3-4-fold in HepG2 cells. This stimulation was mediated through
      the activation of phosphatidylinositol 3-kinase (PI 3-K)/Akt and the inhibition
      of glycogen synthase kinase-3beta (GSK-3beta) since the effects of insulin and
      IGF-1 were inhibited by dominant-negative mutants of PI 3-K or Akt and an
      uninhibitable GSK-3beta. Together with inhibiting GSK-3beta, insulin and IGF-1
      increased the cytoplasmic levels of beta-catenin. The PI 3-K/Akt/GSK-3beta
      pathway was not the sole to mediate insulin and IGF-1 stimulation of Lef/Tcf
      dependent transcription. The Ras signalling pathway was also required as (i) the
      stimulatory effects of insulin and IGF-1 were inhibited by dominant-negative Ras
      or the MEK1 inhibitor PD98059 and (ii) activated Ha-Ras or constitutively active
      MEK1 synergized with catalytically inactive GSK-3beta to stimulate Lef/Tcf
      dependent transcription. This study provides the first evidence that insulin and
      IGF-1 stimulate the beta-catenin pathway through two signalling cascades
      bifurcating downstream of PI 3-K and involving GSK-3beta inhibition and Ras
      activation. These findings demonstrate for the first time the ability of insulin
      and IGF-1 to activate the beta-catenin pathway in hepatoma cells and thereby
      provide new insights into the role of these factors in hepatocarcinogenesis.

PMID- 11313953
TI  - Modulation of apoptosis by procaspase-2 short isoform: selective inhibition of
      chromatin condensation, apoptotic body formation and phosphatidylserine
      externalization.
AB  - Procaspase-2 is one of the cysteine aspartate proteases involved in apoptotic
      cell death. Alternative splicing of CASP-2 messenger RNA generates a long
      isoform, procaspase-2L, whose overexpression induces cell death and a truncated
      isoform, procaspase-2S, whose function remains poorly defined. The present study
      explored the consequences of procaspase-2S overexpression in U937 human leukemic
      cells exposed to the topoisomerase II inhibitor etoposide as an apoptotic
      stimulus. Overexpression of procaspase-2S in U937 cells partially prevented
      nuclear changes associated with etoposide-induced cell death, as determined by
      Hoechst 33342 staining of nuclear chromatin and electron microscopy studies.
      Procaspase-2S also prevented the maturation of apoptotic bodies, delayed
      phosphatidylserine externalization on the plasma membrane and prevented the
      cleavage and activation of procaspase-2L. These effects were not observed when
      the cysteine 289 in the consensus QACRG motif was mutated into a serine. Wild
      type procaspase-2S overexpression did not influence the cleavage of procaspase-3,
      procaspase-7 and poly(ADP-ribose)polymerase nor the fragmentation of nuclear DNA
      into nucleosome-sized fragments. Altogether, these results indicate that the
      short isoform of procaspase-2 negatively interferes with selective features of
      apoptosis, an activity that is suppressed by mutation of the cysteine 289.

PMID- 11313954
TI  - Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro.
AB  - Resistance to apoptosis and ability to promote angiogenesis are integral features
      of the metastatic phenotype. Human gene CC3 is a metastasis suppressor for
      variant small cell lung carcinoma and a mouse melanoma in vivo. We have shown
      previously that metastasis-suppressing function of CC3 might be due at least in
      part to the ability of CC3 protein to predispose tumor cells to apoptosis. Here
      we demonstrate that CC3 has a previously unidentified effect on the ability of
      tumor cells to induce angiogenesis in vitro. Expression of CC3 in three different
      tumor cell lines significantly diminished their angiogenic character as
      manifested in the in vitro proliferation and migration assays with endothelial
      cells of both macro- and microvascular origin. Expression of CC3 induced changes
      in RNA levels of several angiogenic modulators consistent with the overall
      reduction in angiogenic properties. These results indicate that expression of CC3
      has a dual effect on phenotype of tumor cells ultimately inhibiting their
      metastatic potential.

PMID- 11313956
TI  - Characterization of ataxia telangiectasia fibroblasts with extended life-span
      through telomerase expression.
AB  - Ataxia-telangiectasia (A-T) is an autosomal recessive disease characterized by
      progressive cerebellar degeneration, immunodeficiencies, genomic instability and
      gonadal atrophy. A-T patients are hypersensitive to ionizing radiation and have
      an elevated cancer risk. Cells derived from A-T patients require higher levels of
      serum factors, exhibit cytoskeletal defects and undergo premature senescence in
      culture. We show here that expression of the catalytic subunit of telomerase
      (hTERT) in primary A-T patient fibroblasts can rescue the premature senescence
      phenotype. Ectopic expression of hTERT does not rescue the radiosensitivity or
      the telomere fusions in A-T fibroblasts. The hTERT+AT cells also retain the
      characteristic defects in cell-cycle checkpoints, and show increased chromosome
      damage before and after ionizing radiation. Although A-T patients have an
      increased susceptibility to cancer, the expression of hTERT in A-T fibroblasts
      does not stimulate malignant transformation. These immortalized A-T cells provide
      a more stable cell system to investigate the molecular mechanisms underlying the
      cellular phenotypes of Ataxia-telangiectasia.

PMID- 11313957
TI  - Ataxia-telangiectasia: chronic activation of damage-responsive functions is
      reduced by alpha-lipoic acid.
AB  - Cells from patients with the genetic disorder ataxia-telangiectasia (A-T) are
      hypersensitive to ionizing radiation and radiomimetic agents, both of which
      generate reactive oxygen species capable of causing oxidative damage to DNA and
      other macromolecules. We describe in A-T cells constitutive activation of
      pathways that normally respond to genotoxic stress. Basal levels of p53 and
      p21(WAF1/CIP1), phosphorylation on serine 15 of p53, and the Tyr15-phosphorylated
      form of cdc2 are chronically elevated in these cells. Treatment of A-T cells with
      the antioxidant alpha-lipoic acid significantly reduced the levels of these
      proteins, pointing to the involvement of reactive oxygen species in their chronic
      activation. These findings suggest that the absence of functional ATM results in
      a mild but continuous state of oxidative stress, which could account for several
      features of the pleiotropic phenotype of A-T.

PMID- 11313958
TI  - Runx2: a novel oncogenic effector revealed by in vivo complementation and
      retroviral tagging.
AB  - The Runx2 (Cbfa1, Pebp2alphaA, Aml3) gene was previously identified as a frequent
      target for transcriptional activation by proviral insertion in T-cell lymphomas
      of CD2-MYC transgenic mice. We have recently shown that over-expression of the
      full-length, most highly expressed Runx2 isoform in the thymus perturbs T-cell
      development, leads to development of spontaneous lymphomas at low frequency and
      is strongly synergistic with Myc. To gain further insight into the relationship
      of Runx2 to other lymphomagenic pathways, we tested the effect of combining the
      CD2-Runx2 transgene either with a Pim1 transgene (E(mu)-Pim1) or with the p53
      null genotype, as each of these displays independent synergy with Myc. In both
      cases we observed synergistic tumour development. However, Runx2 appeared to have
      a dominant effect on the tumour phenotype in each case, with most tumours
      conforming to the CD3(+), CD8(+), CD4(+/-) phenotype seen in CD2-Runx2 mice.
      Neonatal infection of CD2-Runx2 mice with Moloney murine leukaemia virus (Moloney
      MLV) also led to a dramatic acceleration of tumour onset. Analysis of known
      Moloney MLV target genes in these lymphomas showed a high frequency of
      rearrangement at c-Myc or N-Myc (82%), and a significant number at Pim1 or Pim2
      (23%), and at Pal1/Gfi1 (18%). These results indicate that Runx2 makes a distinct
      contribution to T-cell lymphoma development which does not coincide with any of
      the oncogene complementation groups previously identified by retroviral tagging.

PMID- 11313959
TI  - Mdr1b facilitates p53-mediated cell death and p53 is required for Mdr1b
      upregulation in vivo.
AB  - The mdr1b gene is thought to be a "stress-responsive" gene, however it is unknown
      if this gene is regulated by p53 in the whole animal. Moreover, it is unknown if
      overexpression of mdr1b affects cell survival. The dependence of mdr1b upon p53
      for upregulation was evaluated in p53 knockout mice. Wild-type (wt) or p53-/-
      mice were treated singly or in combination with gamma irradiation (IR) and/or the
      potent DNA damaging agent, diethylnitrosoamine (DEN). Both IR and DEN induced
      mdr1b in wild-type animals, but not in the p53-/- mice. IR also upregulated
      endogenous mdr1b in the H35 liver cell line, and the mdr1b promoter was activated
      by IR and activation correlated with p53 levels; moreover activation required an
      intact p53 binding site. Colony survival studies revealed that co-transfection of
      both mdr1b and p53 dramatically reduced colony numbers compared to cells
      transfected with either p53 or mdr1b alone and cells microinjected with both
      mdr1b and p53 had a more dramatic loss in viability compared to cells injected
      with either expression vector alone. Further studies using acridine orange and
      ethidium bromide to measure apoptosis revealed that mdr1b caused apoptosis and
      this was enhanced by p53, however the increased apoptosis required a functional
      p53 transactivation domain. These studies indicate that mdr1b is a downstream
      target of p53 in the whole animal and expression of mdr1b facilitates p53
      mediated cell death.

PMID- 11313960
TI  - Functional evidence for the presence of tumor suppressor gene on chromosome 10p15
      in human prostate cancers.
AB  - Loss of heterozygosity on chromosome 10p was observed frequently in human
      prostate cancers. Studies have demonstrated that the introduction of the short
      arm of human chromosome 10 into a human prostate cancer cell line, PPC-1, by
      microcell-mediated chromosome transfer (MMCT), suppressed the malignant
      phenotype, suggesting the presence of a prostate tumor suppressor gene(s) within
      a region of 17 cM at distal 10p. To narrow down the candidate region harboring
      the tumor suppressor gene, a series of 10p fragments were transferred into PPC-1
      cells by MMCT using a panel of hamster-human hybrid cells containing various
      portions of 10p. Four of the six hybrid cells obtained showed decreased
      tumorigenicity when injected subcutaneously into athymic nude mice. Tumors
      developed only at six of 40 injection sites for these four hybrid cells. In
      contrast, the other two hybrid cells, as well as parental PPC-1 cells, were
      judged to be fully tumorigenic because tumors appeared at a total 26 of 32 sites
      for the two hybrid cells and 15 of 16 sites for PPC-1. Allelotyping of 10p
      combined with fluorescence in situ hybridization in these hybrid cells suggested
      that a prostate tumor suppressor gene was located within a fragment of
      approximately 1.2 Mb flanked by D10S1172 and D10S226 on 10p15.1.

PMID- 11313961
TI  - Knock-in mice with a chimeric human/murine p53 gene develop normally and show
      wild-type p53 responses to DNA damaging agents: a new biomedical research tool.
AB  - The high prevalence and great diversity of p53 tumor suppressor gene mutations in
      human tumors call for development of therapeutic molecules that rescue function
      of aberrant p53 protein. P53 mutations also offer new approaches to the study of
      the origins of mutations in human cancer. An experimental mouse model with a
      genetically modified but normal functioning p53 gene harboring the human rather
      than the murine core domain, would be of considerable benefit to research on both
      cancer therapeutics and etiology; however, it is uncertain whether such mice
      would permit biological functions of p53 to be retained. Using a Cre/lox P gene
      targeting approach, we have constructed a human p53 knock-in (hupki) mouse strain
      in which exons 4-9 of the endogenous mouse p53 allele were replaced with the
      homologous, normal human p53 gene sequence. The chimeric p53 allele (p53(KI)) is
      properly spliced, transcribed in various tissues at levels equivalent to wild
      type mice, and yields cDNA with the anticipated sequence, that is, with a core
      domain matching that of humans. The hupki p53 protein binds to p53 consensus
      sequences in gel mobility shift assays and accumulates in the nucleus of hupki
      fibroblasts in response to UV irradiation, as is characteristic of wild-type p53.
      Induction of various p53-regulated genes in spleen of gamma-irradiated homozygous
      hupki mice (p53(KI/KI)), and the kinetics of p53-dependent apoptosis in
      thymocytes are similar to results with wild-type (p53(+/+)) mice, further
      indicating normal p53 pathway function in the hupki strain. The mice are
      phenotypically normal and do not develop spontaneous tumors at an early age, in
      contrast to knock-out (p53(-/-)) strains with a defective p53 gene. The chimeric
      (p53(KI)) allele thus appears to provide a biological equivalent to the
      endogenous murine (p53(+)) gene. This strain is a unique tool for examining in
      vivo spontaneous and induced mutations in human p53 gene sequences for comparison
      with published human tumor p53 mutation spectra. In addition, the hupki strain
      paves the way for mouse models in pre-clinical testing of pharmaceuticals
      designed to modulate DNA-binding activity of human p53.

PMID- 11313962
TI  - Hypermethylation of the hMLH1 gene promoter is associated with microsatellite
      instability in early human gastric neoplasia.
AB  - A significant portion of gastric cancers exhibit defective DNA mismatch repair,
      manifested as microsatellite instability (MSI). High-frequency MSI (MSI-H) is
      associated with hypermethylation of the human mut-L homologue 1 (hMLH1) mismatch
      repair gene promoter and diminished hMLH1 expression in advanced gastric cancers.
      However, the relationship between MSI and hMLH1 hypermethylation has not been
      studied in early gastric neoplasms. We therefore investigated hMLH1
      hypermethylation, hMLH1 expression and MSI in a group of early gastric cancers
      and gastric adenomas. Sixty-four early gastric neoplasms were evaluated,
      comprising 28 adenomas, 18 mucosal carcinomas, and 18 carcinomas with superficial
      submucosal invasion but clear margins. MSI was evaluated using multiplex
      fluorescent PCR to amplify loci D2S123, D5S346, D17S250, BAT 25 and BAT 26.
      Methylation-specific PCR was performed to determine the methylation status of
      hMLH1. In two hypermethylated MSI-H cancers, hMLH1 protein expression was also
      evaluated by immunohistochemistry. Six of sixty-four early gastric lesions were
      MSI-H, comprising 1 adenoma, 4 mucosal carcinomas, and 1 carcinoma with
      superficial submucosal invasion. Two lesions (one adenoma and one mucosal
      carcinoma) demonstrated low-frequency MSI (MSI-L). The remaining 56 neoplasms
      were MSI-stable (MSI-S). Six of six MSI-H, one of two MSI-L, and none of thirty
      MSI-S lesions showed hMLH1 hypermethylation (P<0.001). Diminished hMLH1 protein
      expression was demonstrated by immunohistochemistry in two of two MSI-H
      hypermethylated lesions. hMLH1 promoter hypermethylation is significantly
      associated with MSI and diminished hMLH1 expression in early gastric neoplasms.
      MSI and hypermethylation-associated inactivation of hMLH1 are more prevalent in
      early gastric cancers than in gastric adenomas. Thus, hypermethylation-associated
      inactivation of the hMLH1 gene can occur early in gastric carcinogenesis.

PMID- 11313963
TI  - Inhibition of breast and brain cancer cell growth by BCCIPalpha, an
      evolutionarily conserved nuclear protein that interacts with BRCA2.
AB  - BRCA2 is a tumor suppressor gene involved in mammary tumorigenesis. Although
      important functions have been assigned to a few conserved domains of BRCA2,
      little is known about the longest internal conserved domain encoded by exons 14
      24. We identified a novel protein, designated BCCIPalpha, that interacts with
      part of the internal conserved region of human BRCA2. Human BCCIP represents a
      family of proteins that are evolutionarily conserved, and contain three distinct
      domains: an N-terminus acidic domain (NAD) of 30-60 amino acids, an internal
      conserved domain (ICD) of 180-220 amino acids, and a C-terminus variable domain
      (CVD) of 30-60 amino acids. The N-terminal half of the human BCCIP ICD shares
      moderate homology with regions of calmodulin and M-calpain, suggesting that BCCIP
      may also bind Ca. Human cells express both a longer, BCCIPalpha, and a shorter,
      BCCIPbeta, form of the protein, which differ in their CVD. BCCIP is a nuclear
      protein highly expressed in testis. Although BCCIPbeta expression is relatively
      consistent in cancer cells, the expression of BCCIPalpha varies in cancer cell
      lines. The BCCIPalpha gene is located at chromosome 10q25.3-26.2, a region
      frequently altered in brain and other cancers. Furthermore, expression of
      BCCIPalpha inhibits breast and brain cancer cell growth, but fails to inhibit
      HT1080 cells and a non-transformed human skin fibroblast. These results suggest
      that BCCIPalpha is an important cofactor for BRCA2 in tumor suppression.

PMID- 11313964
TI  - Identification of a novel interaction between integrin beta1 and 14-3-3beta.
AB  - Integrins are cell surface receptors for extracellular matrix, which play
      important roles in a variety of biological processes. 14-3-3 proteins are a
      highly conserved family of cytoplasmic proteins that associate with several
      intracellular signaling molecules in regulation of various cellular functions.
      Here, we report identification of an interaction between the integrin beta1
      cytoplasmic domain and 14-3-3beta by using the yeast two-hybrid screen. Like
      several other proteins, the integrin beta1 cytoplasmic domain associated with 14
      3-3beta by a non-phosphoserine mechanism. The 14-3-3beta/integrin beta1
      interaction was confirmed by in vitro binding assays as well as co-precipitation
      in vivo. Furthermore, we found that 14-3-3beta co-localized with integrin beta1
      during the early stage of cell spreading on fibronectin, suggesting a potential
      role of the 14-3-3beta/integrin beta1 interaction in the regulation of cell
      adhesion. Using tetracycline-regulated expression system, we showed that
      overexpression of 14-3-3beta stimulated cell spreading and migration on
      fibronectin but not on poly-L-lysine. However, the induced expression of 14-3
      3beta did not affect tyrosine phosphorylation of FAK or its substrates, p130(cas)
      and paxillin, suggesting that 14-3-3beta regulated integrin-mediated cell
      spreading and migration by FAK-independent mechanisms. Taken together, these
      results identify an interaction between integrin and 14-3-3 proteins and suggest
      a potentially novel cellular function for 14-3-3 proteins in the regulation of
      integrin-mediated cell adhesion and signaling events.

PMID- 11313965
TI  - Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3:
      cleavage of the common alpha subunit during apoptosis.
AB  - Caspase plays an important role in apoptosis. We report here that
      farnesyltransferase/geranylgeranyltransferase (FTase/GGTase)-alpha, a common
      subunit of FTase (alpha/beta(FTase)) and GGTase I (alpha/beta(GGTase)), was
      cleaved by caspase-3 during apoptosis. FTase/GGTase-alpha (49 kDa) was cleaved to
      35 kDa (p35) in the Rat-2/H-ras, W4 and Rat-1 cells treated with FTase inhibitor
      (LB42708), anti-Fas antibody and etoposide, respectively. This cleavage was
      inhibited by caspase-inhibitors (YVAD-cmk, DEVD-cho). Serial N-terminal deletions
      and site-directed mutagenesis showed that Asp59 of FTase/GGTase-alpha was cleaved
      by caspase-3. The common FTase/GGTase-alpha subunit, but not the beta subunits,
      of the FTase or GGTase I protein complexes purified from baculovirus-infected SF
      9 cells was cleaved to be inactivated by purified caspase-3. In contrast, FTase
      mutant protein complex [(D(59)A)alpha/beta(FTase)] was resistant to caspase-3.
      Expression of either the cleavage product (60-379) or anti-sense of FTase/GGTase
      alpha induced cell death in Rat-2/H-ras cells. Furthermore, expression of
      (D(59)A)FTase/GGTase-alpha mutant significantly desensitized cells to etoposide
      induced death. Taken together, we suggest that cleavage of prenyltransferase by
      caspase contributes to the progression of apoptosis.

PMID- 11313966
TI  - Down-regulation of the c-Jun N-terminal kinase (JNK) phosphatase M3/6 and
      activation of JNK by hydrogen peroxide and pyrrolidine dithiocarbamate.
AB  - Oxidative stress activates the c-Jun N-terminal kinase (JNK) pathway. However,
      the exact mechanisms by which reactive oxygen species (ROS) activate JNK are
      unclear. We found that the ability of hydrogen peroxide (H(2)O(2)) to induce JNK
      activation varied in different cell types. Pyrrolidine dithiocarbamate (PDTC), a
      presumed antioxidant, induced JNK activation on its own and enhanced JNK
      activation by H(2)O(2) in many cell types, including Jurkat, HEK293, and LNCaP
      and Tsu-Pr1 prostate cancer cells. The activation of JNK by PDTC, in the presence
      or absence of exogenous H(2)O(2), was dependent on its chelating ability to metal
      ions, most likely copper ions. Despite the strong JNK-activating ability,
      H(2)O(2) plus PDTC did not induce significant activation of the upstream kinases,
      SEK1/MKK4 and MKK7. However, the JNK inactivation rate was slower in cells
      treated with H(2)O(2) plus PDTC compared with the rate in cells treated with
      ultraviolet C (UV-C). Treatment of H(2)O(2) plus PDTC significantly decreased the
      expression levels of a JNK phosphatase, M3/6 (also named hVH-5), but not the
      levels of other phosphatases (PP2A and PP4). In contrast, UV-C irradiation did
      not cause the down-regulation of M3/6. These results suggest that JNK activation
      by H(2)O(2) plus PDTC resulted from the down-regulation of JNK phosphatases. Our
      data also reveal a necessity to carefully evaluate the pharmacological and
      biochemical properties of PDTC.

PMID- 11313967
TI  - Downregulation of MLL-CBP fusion gene expression is associated with
      differentiation of SN-1 cells with t(11;16)(q23;p13).
AB  - The translocation t(11;16)(q23;p13) has only been documented in patients with
      acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA
      topoisomerase II. We have established a myeloid cell line (SN-1) with the MLL-CBP
      fusion gene from an acute leukemia patient with t(11;16)(q23;p13). Although SN-1
      cells were not induced to differentiate by all-trans retinoic acid (ATRA) and
      1alpha,25-dihydroxyvitamin D(3) (VD3), retinoid X receptor (RXR) agonists, such
      as 9-cis retinoic acid and Ro48-2250, effectively induced differentiation of the
      cells. Downregulation of the expression of the MLL-CBP fusion gene occurred
      during the differentiation of SN-1 cells. When SN-1 cells were treated with MLL
      CBP antisense oligonucleotide, the cells were induced to differentiate by ATRA or
      VD3, suggesting that the MLL-CBP fusion gene dominant-negatively suppresses ATRA-
      or VD3-induced differentiation. Moreover, suboptimal concentrations of sodium
      butyrate, a histone deacetylase inhibitor, had a cooperative effect with ATRA or
      VD3 in inducing the differentiation of SN-1 cells. The downregulation of the
      expression of MLL-CBP mRNA was accompanied by the induction of differentiation.
      These findings suggest that RXR agonists or a clinically applicable combination
      of ATRA and butyrate derivatives might be useful for differentiation therapy in
      leukemia patients with the MLL-CBP fusion gene.

PMID- 11313968
TI  - The catalytic activity of dsRNA-dependent protein kinase, PKR, is required for NF
      kappaB activation.
AB  - The double stranded RNA-dependent protein kinase (PKR), in addition to its role
      as a translational controlling factor, is a key transcriptional regulator
      exerting antiviral and antitumoral activities. We have previously shown that
      induction of NF-kappaB by PKR is involved in apoptosis commitment and this
      process is mediated through activation of the IKK complex. To gain insights into
      the mechanism of activation of NF-kappaB by PKR, we have analysed the domains of
      PKR involved in IKK activation and subsequent NF-kappaB induction. In PKR(0/0)
      cells infected with a collection of vaccinia virus (VV) recombinants expressing
      different mutant forms of PKR, we found that only PKR forms conserving the
      catalytic activity are able to activate NF-kappaB. An inactive PKR mutant
      (K296R), was unable to induce NF-kappaB activation despite full expression of the
      protein in a wide range of concentrations, as defined by Western blot, EMSA, IKK
      kinase activity and NF-kappaB transactivation assays. Moreover, the mutant PKR
      (K296R) acts as a dominant negative of PKR-induced eIF-2alpha phosphorylation and
      NF-kappaB activation. However, PKR mutants unable to activate NF-kappaB still
      retain their ability to associate with the IKK complex, as confirmed by
      immunoprecipitation analysis. We conclude that the catalytic activity of PKR and
      not only a protein-protein interaction with the IKK complex, is needed for
      activation of the transcription factor NF-kappaB.

PMID- 11313969
TI  - Do VHL and HIF-1 mirror p53 and Mdm-2? Degradation-transactivation loops of
      oncoproteins and tumor suppressors.
AB  - Recently it has been shown that the VHL tumor suppressor targets the hypoxia
      inducible transcription factor (HIF-1) for ubiquitin-dependent degradation by the
      proteasome. Past mysteries of the p53 tumor suppressor help to solve the present
      puzzles of the VHL tumor suppressor. Thus, Mdm-2 targets the p53 tumor suppressor
      for ubiquitin-dependent degradation by the proteasome, but, in addition, the p53
      transcription factor induces Mdm-2, thus, establishing a feedback loop. Hypoxia
      or DNA damage by abrogating binding of HIF-1 with VHL and p53 with Mdm-2,
      respectively, leads to stabilization and accumulation transcriptionally active
      HIF-1 and p53. More detailed analysis depicts the VHL/HIF-1 pair as the p53/mdm-2
      pair that is turned upside down, suggesting that VHL may be a HIF-1-inducible
      gene of the feedback loop. The extended model proposes that an oncoprotein and a
      tumor suppressor due to transactivation coupled with feedback protein degradation
      might form functional pairs (Rb/E7, E2F/Rb, E2F/Mdm-2, catenin/APC, p27, cyclin
      D1, Rb/gankyrin), thus, predicting missing links.

PMID- 11313970
TI  - Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's
      lymphoma.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and
      tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are
      cell-surface receptors involved in tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes
      have recently been mapped to chromosome 8p21-22, which is a frequent site of
      allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma
      (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte
      homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be
      involved in the development of NHL and that such mutations may be responsible for
      the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire
      coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for
      the detection of the somatic mutations in a series of 117 human NHLs using
      polymerase chain reaction (PCR)-based single strand conformation polymorphism
      (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1
      gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight
      mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected
      in the death domains and one nonsense mutation of TRAIL-R2 was detected just
      before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and
      TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1
      and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome
      8p21-22 in human NHL.

PMID- 11313971
TI  - The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase.
AB  - The monocytic leukemia zinc finger protein (MOZ) gene is rearranged in
      t(8;16)(p11;p13), t(8;22)(p11;q13) and inv(8)(p11q13) associated with acute
      myeloid leukemia. The other fusion partners involved are CBP, p300 and TIF2,
      transcriptional coactivators with known or potential histone acetyltransferase
      (HAT) activity. MOZ itself is a 2004-residue protein containing a putative acetyl
      CoA-binding motif, so it was hypothesized that MOZ is a HAT. Here we present
      direct evidence that MOZ has intrinsic HAT activity. Moreover, MOZ possesses a
      transcriptional repression domain at its N-terminal part and an activation domain
      at its C-terminal part. The activation domain does not show sequence similarity
      to any yeast proteins, but when tethered, it is able to activate transcription in
      yeast. Therefore, MOZ is a HAT with characteristics of a transcriptional
      coregulator, supporting the hypothesis that aberrant acetylation by abnormal MOZ
      proteins leads to leukemogenesis.

PMID- 11313972
TI  - The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits
      human Polycomb 3.
AB  - The translocation t(11;19) is frequently found in acute leukemia in infants. This
      event truncates the proto-oncogene MLL and fuses the 5' end of MLL in frame with
      the ENL gene. ENL contributes a crucial protein-protein interaction domain to the
      resulting oncoprotein MLL-ENL. Here we show by yeast two-hybrid assays, GST-pull
      down experiments and in a far western blot analysis that this domain is necessary
      and sufficient to recruit a novel member of the human Polycomb protein family
      (hPc3). hPc3 RNA was detected throughout the human hematopoietic system. Similar
      to other Polycomb proteins hPc3 acts as a transcriptional repressor. The ENL-hPc3
      interaction was verified by mutual co-precipitation of the proteins from cell
      extracts. ENL and hPc3 tagged with fluorescent proteins co-localized in living
      cells in a nuclear dot pattern. An internal region of hPc3 was responsible for
      binding to ENL. Finally, hPc3 binds to the C-terminus of AF9, another common MLL
      fusion partner. The recruitment of a repressive function by ENL opens up a new
      insight into a possible mechanism of leukemogenesis by the fusion protein MLL
      ENL.

PMID- 11313973
TI  - Mechanism of hyperploid cell formation induced by microtubule inhibiting drug in
      glioma cell lines.
AB  - Checkpoint mechanism plays a crucial role in ensuring genomic integrity during
      cell cycle. Loss of checkpoint function is known to induce genomic instability
      and to alter ploidy of dividing cells. In this study, we examined mechanisms of
      hyperploid formation in glioma cells by treatment with nocodazole, which
      activates spindle assembly checkpoint by inhibiting microtubule polymerization.
      By prolonged nocodazole treatment, U251MG human glioma cell, which has a p53
      mutation, underwent transient arrest at mitosis, and subsequently exited from
      mitotic arrest (termed 'mitotic slippage') followed by DNA replication without
      cytokinesis, resulting in hyperploid formation. Additionally, the heterogeneity
      in the number of centrosomes per cell increased during the hyperploid formation,
      suggesting that these hyperploid cells have genomic instability. By employing
      LN382 glioma cell that has a temperature-sensitive p53 mutation, we found that
      the activation of p53 prevents hyperploid formation after the prolonged
      nocodazole treatment. Furthermore, staurosporine, an inhibitor for a broad range
      of serine/threonine kinases including cdc2, was found to enhance hyperploid
      formation in U251MG cells by accelerating the induction of mitotic slippage.
      Interestingly, inhibitors specific for cdc2 kinase prevented the G2 to M
      transition but did not accelerate mitotic slippage, suggesting that staurosporine
      sensitive kinases other than cdc2 are required for maintenance of spindle
      assembly checkpoint. Moreover, the enhancement of hyperploid formation by
      staurosporine was also blocked by p53-dependent G1 checkpoint. These results
      suggest that abrogation of G1 checkpoint is a critical factor for formation of
      hyperploid cells after the mitotic slippage.

PMID- 11313974
TI  - Reciprocal down-regulation of p53 and SOD2 gene expression-implication in p53
      mediated apoptosis.
AB  - p53 regulates the transcription of a number of genes among which are different
      redox-related genes. It has been proposed that these genes can induce a cellular
      oxidative stress leading to p53-dependent apoptosis (Polyak et al., 1997). MnSOD,
      the product of superoxide dismutase 2 (SOD2) gene, is one of the major cellular
      defences against oxidative stress. We demonstrate here that p53 is able to
      repress SOD2 gene expression and that this repression takes place at promoter
      level. We show the importance of this regulation for the p53 function, by
      demonstrating that an overexpression of MnSOD decreases p53-mediated induction of
      apoptosis. Moreover, we demonstrate that MnSOD overexpression decreases p53-gene
      expression at the promoter level. These findings raise the hypothesis that p53
      and SOD2 genes are mutually regulated leading to the modulation of various
      cellular processes including apoptosis.

PMID- 11313975
TI  - Identification of a novel transcriptional repressor element located in the first
      intron of the human BRCA1 gene.
AB  - Loss or lowered expression of BRCA1 in non-familial breast cancer has been shown
      in several recent studies. Understanding how BRCA1 expression is regulated should
      provide new insights into the role of BRCA1 in sporadic breast cancer. We have
      recently identified a critical 18-base pair (bp) DNA element within the minimal
      BRCA1 promoter whereupon the formation of a specific protein-DNA complex and
      transcription of BRCA1 is dependent. We now report a non tissue-specific
      transcriptional repressor activity, located more than 500 bp into the first
      intron of BRCA1. Progressive deletions from the 3'-end of intron 1 and reporter
      gene assays localized the repressor activity to an 83-bp region. Electrophoretic
      mobility shift assays with this 83 bp DNA and various sub-fragments of it showed
      binding of nuclear proteins to a 36 bp BstNI-BseRI fragment. Functional
      transcriptional repression by this 36 bp DNA could be conferred on a heterologous
      thymidine kinase promoter. Analysis of multiple reporter gene constructs
      containing the BRCA1 genomic region driving transcription in both directions
      suggests that the putative negative regulatory element functions to block
      transcription only in the BRCA1 direction, although the promoter is shared by the
      divergently transcribed NBR2 gene.

PMID- 11313976
TI  - Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis
      (desmoid tumor).
AB  - Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five
      per cent of cases harbor a somatic mutation in either the APC or beta-catenin
      genes, resulting in beta-catenin protein stabilization. Cyclooxygenase-2 (COX-2)
      is an enzyme involved in prostaglandin synthesis that modulates the formation of
      colonic neoplasia, especially in cases due to mutations resulting in beta-catenin
      stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N
      mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2
      levels. COX-2 blockade either by the selective agent DFU or by non-selective COX
      blocking agents results in reduced proliferation in human tumor cell cultures.
      Breeding mice with Cox-2-/- mice resulted in no difference in number of
      aggressive fibromatoses formed, but in a smaller tumor size, while there was a
      decrease in number of GI lesions by 50%. Mice fed various COX blocking agents
      also showed a decline in tumor size. COX-2 expression was regulated by tcf
      dependent transcription in this lesion. COX-2 partially regulates proliferation
      due to beta-catenin stabilization in aggressive fibromatosis. Although COX
      blockade alone does not cause tumor regression, this data suggests that it may
      have a role as an adjuvant therapy to slow tumor growth in this lesion.

PMID- 11313977
TI  - Muc4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu,
      potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted
      tumor.
AB  - Overexpression of the membrane mucin MUC4/Sialomucin complex (SMC) has been
      observed during malignant progression of mammary tumors in both humans and rats,
      suggesting that deregulation of MUC4/SMC expression might facilitate development
      of these malignancies. As previously reported, overexpression of SMC results in
      suppression of both cell adhesion and immune killing of tumor cells. SMC also
      acts as a ligand for ErbB2/Neu, modulating phosphorylation of the receptor
      tyrosine kinase in the presence and absence of heregulin. The present studies
      investigated the effect of Muc4/SMC up-regulation on primary tumor growth using a
      tetracycline-inducible SMC expression system in a xenotransplanted tumor model.
      SMC up-regulation provoked rapid growth of transfected A375 melanoma in nude
      mice. Up-regulation of SMC, however, did not significantly increase proliferation
      of A375 cells in vitro. Instead, a strong suppression of apoptosis was observed
      in situ in SMC-overexpressing tumors. These data suggest that Muc4/SMC expression
      promotes tumor growth in vivo at least in part via suppression of tumor cell
      apoptosis. Importantly, reduction of apoptosis was also observed in vitro,
      indicating that anti-apoptotic effect of SMC is independent of tumor-host
      interactions. These findings strongly suggest that SMC up-regulation alters
      intracellular signaling to favor cell survival, providing for the first time
      evidence for the regulation of programmed cell death by a gene of the MUC family.

PMID- 11313978
TI  - Smads mediate signaling of the TGFbeta superfamily in normal keratinocytes but
      are lost during skin chemical carcinogenesis.
AB  - The Smads are the signaling mediators of the TGFbeta superfamily. In the present
      study, we examined Smad expression in mouse epidermis and chemically-induced skin
      tumors. Mutations in Smad2 and -4 genes were also screened. Transcripts of Smad1
      through -5 were constantly expressed in the epidermis regardless of changes in
      TGFbeta signaling, state of differentiation and stages of carcinogenesis. Smad7
      transcripts were barely detectable in keratinocytes, but were induced by TGFbeta1
      treatment and in chemically-induced skin tumors. At the protein level, Smad1 was
      detected throughout the epidermis, whereas Smad2 through -5 exhibited greater
      levels in suprabasal layers than basal keratinocytes. In cultured keratinocytes,
      Smad2, -3 and -4 underwent nuclear translocation upon TGFbeta1 treatment.
      Furthermore, nuclear translocation of Smads correlated with decreased BrdU
      labeling in proliferative keratinocytes. Although no mutations were detected in
      the Smad2 and -4 genes in tumors, proteins of Smad1 through -5 were partially or
      completely lost in carcinomas. These data document that Smads are expressed at
      high levels in the epidermis and mediate signaling of the TGFbeta superfamily.
      During skin carcinogenesis, loss of Smad1 through -5 and overexpression of Smad7
      may contribute to the loss of growth inhibition mediated by TGFbeta superfamily
      members, thus resulting in tumor progression.

PMID- 11313979
TI  - p15(PAF), a novel PCNA associated factor with increased expression in tumor
      tissues.
AB  - Proliferating cell nuclear antigen (PCNA) is an essential protein in both DNA
      replication and DNA damage repair. A novel 15 kD protein, p15(PAF), was
      identified as a PCNA-associated factor in a yeast two-hybrid screen using PCNA as
      the bait. p15(PAF) is localized primarily in the nucleus. p15(PAF) shares the
      conserved PCNA binding motif with several other PCNA binding proteins including
      CDK inhibitor p21. Overexpression of p15(PAF) competes with p21-PCNA binding.
      Mutation of this motif in p15(PAF) abolished its PCNA-binding activity. Notably,
      p15(PAF) expression in several types of tumor tissues was significantly
      increased, especially in esophageal tumors. Like PCNA, p15(PAF) may possess
      prognostic significance in a broad array of human cancers.

PMID- 11313980
TI  - Mechanisms of regulation of cell adhesion and motility by insulin receptor
      substrate-1 in prostate cancer cells.
AB  - LNCaP cells are human prostatic cancer cells that have a frame-shift mutation of
      the tumor suppressor gene PTEN and do not express the insulin receptor substrate
      1 (IRS-1), a major substrate of the type 1 insulin-like growth factor receptor
      (IGF-IR). Ectopic expression of IRS-1 in LNCaP cells increases cell adhesion and
      decreases cell motility by an IGF-I-independent mechanism. We show now that these
      effects of IRS-1 are accompanied by serine phosphorylation of IRS-1 and are
      inhibited by inhibitors of phosphatidylinositol 3-kinase (PI3K). We have
      confirmed the requirement for PI3K activity and serine phosphorylation by the use
      of IRS-1 mutants, expressed in LNCaP cells. Serine phosphorylation inhibits IGF-I
      induced tyrosyl phosphorylation of IRS-1, which is restored by the expression of
      wild-type PTEN or by inhibition of PI3K activity. Finally, IRS-1 in LNCaP cells
      co-immunoprecipitates with integrin alpha 5 beta 1, and the association is again
      IGF-I-independent. We conclude that in LNCaP cells, IRS-1 is serine
      phosphorylated by PI3K, generating effects that are different, and even opposite,
      from those generated by IGF-I.

PMID- 11313981
TI  - p53 mutants exhibiting enhanced transcriptional activation and altered promoter
      selectivity are revealed using a sensitive, yeast-based functional assay.
AB  - Changes in promoter specificity and binding affinity that may be associated with
      p53 mutations or post-translational modifications are useful in understanding p53
      structure/function relationships and categorizing tumor mutations. We have
      exploited variable expression of human p53 in yeast to identify mutants with
      novel phenotypes that would correspond to altered promoter selectivity and
      affinity. The p53 cDNA regions coding for the DNA binding and tetramerization
      domains were subjected to random PCR mutagenesis and were cloned directly by
      recombination in yeast into a vector with a GAL1 promoter whose level of
      expression could be easily varied. p53 variants exhibiting higher than wild type
      levels of transactivation (supertrans) for the RGC responsive element were
      identified at low level of p53 protein expression. All the p53 mutants obtained
      with this screen were located in the DNA binding domain. Two out of 17 supertrans
      mutants have been found in tumors. Six mutations were in the L1 loop region
      between amino acids 115 and 124. The transactivation potential of a panel of
      supertrans p53 mutants on different promoters was evaluated using the p53
      responsive elements, RGC, PIG3, p21 and bax. Although all mutants retained some
      activity with all promoters, we found different patterns of induction based on
      strength and promoter specificity. In particular none of the mutants was
      supertrans for the p21 responsive element. Interestingly, further analysis in
      yeast showed that the transactivation function could be retained even in the
      presence of dominant-negative p53 tumor mutations that could inhibit wild type
      p53. Five mutants were also characterized in human cells in terms of growth
      suppression and transactivation of various promoters. These novel supertrans p53
      mutants may be useful in studies aimed at dissecting p53 downstream pathways,
      understanding specific interactions between p53 and the DNA, and could replace
      wild type p53 in cancer gene therapy protocols. The approach may also prove
      useful in identifying p53 tumor mutations.

PMID- 11313982
TI  - Transactivation-deficient p73alpha (p73Deltaexon2) inhibits apoptosis and
      competes with p53.
AB  - p73 has recently been identified as a structural and functional homolog of the
      tumor suppressor protein p53. Overexpression of p53 activates transcription of
      p53 effector genes, causes growth inhibition and induced apoptosis. We describe
      here the effects of a tumor-derived truncated transcript of p73alpha
      (p73Deltaexon2) on p53 function and on cell death. This transcript, which lacks
      the acidic N-terminus corresponding to the transactivation domain of p53, was
      initially detected in a neuroblastoma cell line. Overexpression of p73Deltaexon2
      partially protects lymphoblastoid cells against apoptosis induced by anti-Fas
      antibody or cisplatin. By cotransfecting p73Deltaexon2 with wild-type p53 in the
      p53 null line Saos 2, we found that this truncated transcript reduces the ability
      of wild-type p53 to promote apoptosis. This anti-apoptotic effect was also
      observed when p73Deltaexon2 was co-transfected with full-length p73 (p73alpha).
      This was further substantiated by suppression of p53 transactivation of the
      effector gene p21/Waf1 in p73Deltaexon2 transfected cells and by inhibition of
      expression of a reporter gene under the control of the p53 promoter. Thus, this
      truncated form of p73 can act as a dominant-negative agent towards
      transactivation by p53 and p73alpha, highlighting the potential implications of
      these findings for p53 signaling pathway. Furthermore, we demonstrate the
      existence of a p73Deltaexon2 transcript in a very significant proportion (46%) of
      breast cancer cell lines. However, a large spectrum of normal and malignant
      tissues need to be surveyed to determine whether this transdominant p73 variant
      occurs in a tumor-specific manner.

PMID- 11313983
TI  - Characterization of the promoter region of the viral interferon regulatory factor
      encoded by Kaposi's sarcoma-associated herpesvirus.
AB  - Viral interferon regulatory factor (vIRF) encoded by Kaposi's sarcoma-associated
      herpesvirus (KSHV) inhibits the expression of interferon-responsive genes, causes
      cellular transformation and transactivates KSHV genes. In the present study, we
      characterized the mRNA expression pattern of the vIRF gene and its promoter. A
      vIRF transcript of 1.7 kb in size was detected in low level in uninduced KSHV
      infected cells and its expression was inducible by 12-O-tetradecanoylphorbol-13
      acetate (TPA), sensitive to cycloheximide and resistant to phosphonoacetic acid.
      The transcription start site was mapped to 79 nt upstream of the ATG initiation
      site by 5'-RACE. Mutagenesis analysis identified a region between -56 and the
      transcription start site (+1) as the minimal promoter region that contains a
      functional TATA box at -27. A region between -337 and -125 contains a repressor
      domain negated by sequence from -991 to -499 in BCBL-1 cells, a region which was
      also identified to be responsive to TPA induction. These results demonstrate vIRF
      as a KSHV early gene, identify its promoter and define the promoter regions that
      contain regulatory elements controlling vIRF transcription.

PMID- 11313984
TI  - Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal
      urothelium and an early and frequent alteration in bladder cancer.
AB  - Transcriptional silencing by CpG island hypermethylation of gene regulatory
      regions is one mechanism for inactivation of tumour suppressor genes. Chromosome
      9q deletion is frequently found in transitional cell carcinoma (TCC) of the
      bladder and upper urinary tract and one of the putative tumour suppressor loci
      has been mapped to 9q32-33. A gene designated as DBCCR1 was identified in the
      candidate region and its mRNA expression is thought to be suppressed by
      hypermethylation. To understand the role of hypermethylation in TCC, we evaluated
      the methylation status of 20 CpG sites of the DBCCR1 5'-CpG island region in a
      total of 69 tumours from 45 patients, 21 normal urothelial specimens, and six
      bladder cancer cell lines. Aberrant hypermethylation levels were found in 36
      (52%) of 69 tumours without any association with tumour grade or stage.
      Methylation was weakly detected in the normal urothelium in association with
      ageing. Although recurrent tumours tended to have higher methylation levels than
      the initial tumours, the methylation pattern was mostly maintained between
      multifocal TCCs in individual patients. The results suggest that hypermethylation
      of the DBCCR1 region is one of the earliest alterations in the development of
      TCCs and there may be an age-related hypermethylation-based field defect in
      normal urothelium. Methylator or methylation-resistant phenotype seems to be
      maintained during multifocal development or recurrence of most TCCs.

PMID- 11313985
TI  - Mouse mismatch repair gene Msh2 is not essential for transcription-coupled repair
      of UV-induced cyclobutane pyrimidine dimers.
AB  - The human mutS homolog gene MSH2 is essential for DNA mismatch repair (MMR) and
      defects in this gene can result in increased mutagenesis, genomic instability and
      hereditary nonpolyposis colorectal cancer (HNPCC). Besides correcting mismatch
      errors arising from DNA replication, it was shown that deficiencies in bacterial
      and human MMR genes including MSH2 resulted in defective transcription-coupled
      repair (TCR) of UV-induced photolesions. Here we show that MMR-deficient
      fibroblasts derived from two independent isogenic mouse strains with defined Msh2
      deficiencies are as proficient in TCR of UV-induced cyclobutane pyrimidine dimers
      (CPD) as wildtype fibroblasts. Our results indicate that in mouse cells Msh2 is
      not essential for TCR of UV-induced CPD in contrast to bacteria and human cells
      and suggest that the biological effects of UV in mouse Msh2(-/-) cells and mice
      are not due to defective TCR.

PMID- 11313986
TI  - Regulation of the Cdc25A gene by the human papillomavirus Type 16 E7 oncogene.
AB  - Cdc25A is a tyrosine phosphatase that is involved in the regulation of the G1/S
      phase transition by activating cyclin E/Cdk2 and cyclin A/Cdk2 complexes through
      removal of inhibitory phosphorylations. The E6 and E7 oncoproteins of the high
      risk human papillomaviruses (HPV) interact with and functionally abrogate the p53
      and pRB proteins, respectively. In the present study we have investigated the
      regulation of the Cdc25A promoter during G1 and S-phases of the cell cycle and by
      the HPV-16 E7 oncoprotein. Serum induction leads to a derepression of the Cdc25A
      promoter and can be mediated through two E2F binding sites, E2F-A and E2F-C.
      While E2F-A is by both E2F1 and E2F4, E2F-C is regulated only by E2F1. The Cdc25A
      promoter is transactivated by the E7 oncogene of HPV-16. Furthermore, Cdc25A
      levels are highly increased in E7-expressing cell lines. Inducible expression of
      E7 leads to an immediate increase in Cdc25A protein levels. These data suggest
      that Cdc25A may be a critical target of HPV-16 E7 in the disruption of the G1/S
      phase transition.

PMID- 11313987
TI  - Human cyclin C protein is stabilized by its associated kinase cdk8, independently
      of its catalytic activity.
AB  - Cyclin C belongs to the cyclin family of proteins that control cell cycle
      transitions through activation of specific catalytic subunits, the cyclin
      dependent kinases (CDKs). However, there is as yet no evidence for any role of
      cyclin C and its partner, cdk8, in cell cycle regulation. Rather, the cyclin C
      cdk8 complex was found associated with the RNA polymerase II transcription
      machinery. The periodic degradation of bona fide cyclins is crucial for cell
      cycle progression and depends on the catalytic activity of the associated CDK.
      Here we show that endogenous cyclin C protein is quite stable with a half-life of
      4 h. In contrast, exogenously expressed cyclin C is very unstable (half-life 15
      min) and degraded by the ubiquitin-proteasome pathway. Co-expression with its
      associated cdk, however, strongly stabilizes cyclin C and results in a protein
      half-life near that of endogenous cyclin C. In stark contrast to data reported
      for other members of the cyclin family, both catalytically active and inactive
      cdk8 induce cyclin C stabilization. Moreover, this stabilization is accompanied
      in both cases by phosphorylation of the cyclin, which is not detectable when
      unstable. Our results indicate that cyclin C has apparently diverged from other
      cyclins in the regulation of its stability by its CDK partner.

PMID- 11313988
TI  - p21(waf1/cip1)-null human fibroblasts are deficient in nucleotide excision repair
      downstream the recruitment of PCNA to DNA repair sites.
AB  - The cyclin-dependent kinase inhibitor p21(waf1/cip1) is known to impair DNA
      synthesis by binding to PCNA, the co-factor of DNA polymerases delta and epsilon.
      However, a positive role for p21 in nucleotide excision repair (NER) has been
      suggested. In this study, the sensitivity to DNA damage and DNA repair efficiency
      were investigated in p21-null human fibroblasts obtained by targeted homologous
      recombination. After UV-C irradiation, p21-/- cells showed a threefold reduction
      in clonogenic survival and an increased susceptibility to apoptosis, as compared
      with parental p21+/+ cells. Removal of cyclobutane pyrimidine dimers was
      significantly reduced in p21-/- cells both in the whole genome, and at the level
      of the rDNA gene cluster, as determined by immunoassay and Southern blot,
      respectively. After DNA damage, the recruitment of PCNA as detergent-insoluble
      form associated to DNA repair sites in p21-/- fibroblasts, was comparable to that
      observed in parental p21+/+ cells. However, PCNA remained associated with DNA for
      a longer period in p21-/- than in p21+/+ cells. These results suggest that in
      human cells, p21 is required for NER at a step located downstream the recruitment
      of PCNA to DNA repair sites.

PMID- 11313989
TI  - p53 upregulates cFLIP, inhibits transcription of NF-kappaB-regulated genes and
      induces caspase-8-independent cell death in DLD-1 cells.
AB  - One of the main functions of the tumor suppressor p53 is the induction of
      programmed cell death. Here we investigated in detail the molecular mechanisms
      that underlay p53 transactivation-dependent apoptosis in the human colon cancer
      cell line DLD-1. Although p53 upregulated the death receptors Fas, TRAIL-R1 and
      TRAIL-R2 in this cell line, p53-induced cell death occurred without detectable
      caspase-8 activation whereas, activation of caspase-9 and caspase-3 was readily
      observed. In addition to the upregulation of death receptors, p53 induced the pro
      apoptotic Bcl-2 family members Bik and Bak and downregulated the anti-apoptotic
      Bcl-xL protein. Moreover, in RNase protection assay analyses as well as in
      reporter gene analyses we found a p53-dependent upregulation of the death
      receptor-inhibitory protein cFLIP. Together, these data argue for a p53-mediated
      activation of the mitochondrial pathway of apoptosis. In contrast to recently
      published data obtained in different cellular systems, there was no evidence for
      an essential role of NF-kappaB in p53-induced cell death. Moreover, induction of
      p53 interfered with TNF-induced NF-kappaB activation independently from apoptosis
      induction.

PMID- 11313990
TI  - Structural and functional involvement of p53 in BER in vitro and in vivo.
AB  - p53 is involved in several DNA repair pathways. Some of these require the
      specific transactivation of p53-dependent genes and others involve direct
      interactions between the p53 protein and DNA repair associated proteins.
      Previously, we have shown that p53 acts directly in Base Excision Repair (BER)
      when assayed under in vitro conditions. Our present data indicate that this
      involvement is independent of the transcriptional activity of the p53 molecule.
      We found that under both in vitro and in vivo conditions, a p53 transactivation
      deficient molecule, p53-22-23 was more efficient in BER activity than was wild
      type p53. However, mutations in the core domain or C-terminal alterations
      strongly reduced p53-mediated BER activity. These results are consistent with the
      hypothesis that the involvement of p53 in BER activity, a housekeeping DNA repair
      pathway, is a prompt and immediate one that does not involve the activation of
      p53 transactivation-dependent mechanisms, but rather concerns with the p53
      protein itself. In an endogenous DNA damage status p53 is active in BER pathways
      as a protein and not as a transcription factor.

PMID- 11313991
TI  - CD30-mediated cell cycle arrest associated with induced expression of
      p21(CIP1/WAF1) in the anaplastic large cell lymphoma cell line Karpas 299.
AB  - One of the major characteristics of anaplastic large cell lymphomas (ALCL) is the
      expression of the Ki-1/CD30 antigen. While the receptor mediates NF-kappaB
      activation in Hodgkin's lymphomas, some data suggest the CD30-mediated apoptosis
      of other CD30-expressing cells. We were able to demonstrate that activation of
      CD30 leads to different effects regarding cell proliferation of the ALCL-derived
      cell lines Karpas 299 and JB6. Western and Northern blotting analysis revealed
      that CD30-induced growth inhibition of Karpas 299 cells correlated with a strong
      upregulation of the cell cycle inhibitor p21(CIP1/WAF1). We found a non
      activating point mutation at codon 273 in exon 8 of the p53 gene in Karpas 299
      cells which indicates an p53-independent mechanism for induced p21 expression.
      Abundant p21 protein expression resulted in hypophosphorylation of the
      retinoblastoma protein (Rb) and inhibition of the proliferating cell nuclear
      antigen (PCNA). CD30-stimulated cells showed no indications of apoptotic cell
      death, like genomic DNA fragmentation or cleavage of the caspase-3 target protein
      poly (ADP-ribose) polymerase (PARP). Our results indicate that CD30 is able to
      mediate an p21-associated cell cycle arrest in ALCL with possible implications
      for prognosis and clinical treatment.

PMID- 11313992
TI  - The RFG oligomerization domain mediates kinase activation and re-localization of
      the RET/PTC3 oncoprotein to the plasma membrane.
AB  - The RET/PTC3 oncogene arises from the fusion between the N-terminal encoding
      domain of the RFG gene and the tyrosine kinase encoding domain of RET receptor.
      RET/PTC3 is very frequent in papillary thyroid carcinomas, especially in children
      exposed to the Chernobyl accident. We have studied the functional consequences of
      the RFG-RET fusion. Here we show that the N-terminal coiled-coil domain of RGF
      mediates oligomerization and activation of the kinase and of the transforming
      capability of RET/PTC3. In addition, the RFG coiled-coil domain mediates a
      physical association between RET/PTC3 and RGF proteins, rendering RFG a bona fide
      substrate of RET/PTC3 kinase. Finally, we show that the coiled-coil domain of RGF
      is essential for the distribution of the RET/PTC3 protein at the
      membrane/particulate cell compartment level, where also most of the RFG protein
      is localized. We propose that fusion to the RFG coiled-coil domain provides RET
      kinase with a scaffold that mediates oligomerization and re-localization of the
      RET/PTC3 protein, a process that may be crucial for the signalling of this
      specific RET/PTC variant.

PMID- 11313993
TI  - Glial tumor cell adhesion is mediated by binding of the FNIII domain of receptor
      protein tyrosine phosphatase beta (RPTPbeta) to tenascin C.
AB  - The extracellular domain of receptor protein tyrosine phosphatase beta (RPTPbeta)
      is composed of several domains which mediate its interactions with distinct
      ligands present on the surface of either neurons or glial cells. Here, we
      demonstrate that the fibronectin type III domain (FNIII) of RPTPbeta binds to
      glial tumor-derived cell lines and primary astrocytes. We used affinity
      purification to isolate several proteins that specifically bind to the FNIII
      domain of RPTPbeta. One of these, a 240 kDa protein that was purified from U118MG
      glioblastoma cell, was identified as tenascin C based on the amino acid sequence
      of several tryptic peptides. The interaction of RPTPbeta with tenascin C was
      found to mediate cell adhesion. Adhesion and spreading of SF763T astrocytoma
      cells expressing RPTPbeta on tenascin C was specifically abolished by the
      addition of a soluble fragment containing the FNIII domain of the receptor.
      RPTPbeta-dependent cell adhesion was mediated by binding to the alternatively
      spliced FNIII repeats A1,2,4 (TnfnA1,2,4) of tenascin C. Furthermore, COS cells
      expressing RPTPbeta adhere to TnfnA1,2,4, while the parental cells did not. These
      results demonstrate that the FNIII domain of RPTPbeta binds to tenascin C and
      suggest that RPTPbeta present on glial tumor cells is a primary adhesion receptor
      system to the extracellular matrix.

PMID- 11313994
TI  - Elevated mutant frequencies and increased C : G-->T : A transitions in Mlh1-/-
      versus Pms2-/- murine small intestinal epithelial cells.
AB  - Mutations in DNA mismatch repair (MMR) genes are associated with increased
      genomic instability and susceptibility to cancer. Mice rendered deficient in
      either Mlh1 or Pms2 as a result of gene targeting are prone to tumorigenesis,
      particularly, lymphomas. In addition, although Mlh1-/- mice also develop small
      intestinal adenomas and adenocarcinomas, Pms2-/- animals remain free of such
      tumors. To establish whether this phenotypic dichotomy might be associated with a
      quantitative and/or qualitative difference in genomic instability in these mice,
      we determined small intestinal epithelial cell DNA mutant frequency and mutation
      spectrum using a transgenic lambda-phage lacI reporter system. Mutant frequencies
      obtained from both Mlh1-/- and Pms2-/- mice revealed elevations of 18- and 13
      fold, respectively, as compared to their wild-type littermates. Interestingly, we
      found that C : G-->T : A transitions were significantly elevated in Mlh1-/- mice,
      accounting in large measure for the 1.5-fold lacI mutant frequency increase seen
      in these animals. We hypothesize that the increased level of C : G-->T : A
      mutations may explain, in part, why Mlh1-/- mice, but not Pms2-/- mice, develop
      small intestinal tumors. Furthermore, the difference in the lacI mutational
      spectrum of Mlh1-/- and Pms2-/- mice suggests that other MutL-like heterodimers
      may play important roles in the repair of G : T mispairs arising within murine
      small intestinal epithelial cells.

PMID- 11313995
TI  - PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors.
AB  - The aberrant transcription factors associated with many human malignancies
      function by deregulation of tumorigenic pathways. However, identification of
      these pathways has come slowly. Virtually all cases of Ewing's Sarcoma and
      peripheral Primitive Neuroectodermal Tumor (PNET) are associated with aberrant
      transcription factors which fuse amino-terminal EWS with the DNA binding moiety
      of an ETS transcription factor (FLI-1 in 90% of cases). Attempts to identify the
      downstream targets of these chimeras in the Ewing Family Tumors (EFT) on the
      basis of differential gene regulation have produced little association with tumor
      biology. As an alternative approach, we have used highly efficient retroviral
      systems to biologically screen cDNA derived from cells transformed by EWS/FLI-1.
      We have identified the recently described PDGF-C as target of EWS/ETS
      transcriptional deregulation. This transcriptional deregulation is specific to
      EWS/FLI. PDGF-C possesses substantial biologic activity in vitro and in vivo. It
      is expressed in EFT cell lines and in primary tumors. Within these EFT cell
      lines, PDGF-C expression is dependent upon EWS/FLI activity. These results
      suggest that PDGF-C may be a significant mediator of EWS/FLI driven oncogenesis.

PMID- 11313996
TI  - Mechanism of repression of squamous differentiation marker, SPRR1B, in malignant
      bronchial epithelial cells: role of critical TRE-sites and its transacting
      factors.
AB  - The overexpression of SPRR1B in bronchial epithelium is a marker for early
      metaplastic changes and the loss of its expression is associated with an
      irreversible malignant transformation. In the present study, we have used a model
      system consisting of normal and malignant bronchial epithelial (BE) cells to
      elucidate the differential transcriptional control of SPRR1B. SPRR1B expression
      is either detectable or PMA (phorbol 13-myristate 12-acetate) -inducible in
      several malignant BE cells including squamous, adeno, small and large cell
      carcinomas. Loss of SPRR1B expression is correlated well with the lack of strong
      in vivo protein-DNA interactions at the -152 bp promoter, which contains two
      functional TRE sites. Even though the basal level AP-1 protein DNA binding
      pattern is different between normal and malignant cells, PMA significantly
      enhances Jun and Fos binding to the consensus TRE site in both cell types.
      Intriguingly, the composition of AP-1 protein binding to the -152 to -86 bp
      SPRR1B promoter is quite different. In untreated cells, SPRR1B promoter is
      predominantly occupied by JunD and Fra2. PMA significantly induced binding of
      JunB and Fra1 in normal cells, while JunB and Fra2 bound to TREs in the malignant
      cells. Overexpression of fra1 in malignant cells significantly enhanced SPRR1B
      promoter activity. In contrast, overexpression of fra2, but not fra1, strongly
      reduced both basal and PMA-inducible promoter activities in normal cells.
      Together, these results indicate that either temporal expression and/or
      differential activation of AP-1 proteins, especially Fra1 and Fra2, might
      contribute to the dysregulation of terminal differentiation marker, SPRR1B,
      expression in various BE cells.

PMID- 11313997
TI  - The nonsteroidal anti-inflammatory drugs aspirin and indomethacin attenuate beta
      catenin/TCF-4 signaling.
AB  - Increasing epidemiological and experimental evidence implicates non-steroidal
      anti-inflammatory drugs (NSAIDs) as anti-tumorigenic agents. The precise
      mechanisms whereby NSAIDs exert their anti-neoplastic effects remain poorly
      understood. Studies from hereditary and sporadic colorectal cancer (CRC) patients
      suggest that NSAIDs may interfere with initiating steps of carcinogenesis, i.e.
      disturbances within the beta-catenin signaling pathway. We therefore investigated
      beta-catenin/TCF signaling in response to aspirin or indomethacin, respectively,
      in four CRC cell lines (SW948, SW480, HCT116, LoVo). Both, aspirin and
      indomethacin inhibited transcription of a beta-catenin/TCF-responsive reporter
      gene in a dose dependent manner. In addition, the beta-catenin/TCF
      transcriptional target cyclin D1 was downregulated by both drugs. Endogenous beta
      catenin levels remained unaffected by either drug. Moreover, indirect
      immunofluorescence studies revealed no significant changes of subcellular beta
      catenin localization in either cell line after NSAID treatment. Likewise, binding
      of the beta-catenin/TCF complex to its specific DNA-binding sites was not
      altered, as demonstrated by electrophoretic mobility shift assay (EMSA) of
      nuclear extracts derived from NSAID treated cells. These results strongly suggest
      that aspirin and indomethacin attenuate the transcription of beta-catenin/TCF
      responsive genes, by modulating TCF activity without disrupting beta-catenin/TCF
      complex formation.

PMID- 11313998
TI  - Abnormalities of the ARF-p53 pathway in oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is associated with heavy smoking and
      drinking, but the molecular pathway of tumorigenesis is not understood.
      Inactivation of the p53 tumor suppressor gene is likely to play an important role
      since p53 mutation is frequently found. The p14ARF tumor suppressor gene is
      functionally linked to p53, because it is activated by oncogenes and causes p53
      dependent growth arrest and apoptosis. The relationship between p14ARF and p53
      inactivation has not been described for OSCC. We studied 25 cases of OSCC to
      determine if there is an inverse correlation between p53 mutation and p14ARF
      inactivation by homozygous deletion or mutation. p53 mutation was found in 16 of
      25 cases (64%), including nine missense and seven truncating mutations. While all
      cases with missense mutations showed abnormal accumulation of p53 protein, there
      were also five carcinomas which showed increased p53 staining in the absence of
      mutation. p14ARF deletion or mutation was found in eight cases (32%), six of
      which also demonstrated p53 mutation. Our findings indicate that OSCC often
      involves loss of both p14ARF and p53 function and suggest that inactivation of
      these two tumor suppressor genes are not functionally equivalent during
      tumorigenesis.

PMID- 11313999
TI  - A transcriptional activation function of p53 is dispensable for and inhibitory of
      its apoptotic function.
AB  - The tumor suppressor p53 is an inducer of cell cycle arrest and programmed cell
      death (apoptosis). The ability of p53 to induce cell cycle arrest is linked to
      its ability to induce transcription of genes such as the cyclin-dependent kinase
      inhibitor p21. However, the dependence of p53-mediated apoptosis on
      transcriptional activation remains controversial. Ectopic expression of a
      temperature-sensitive (ts) p53 allele induced expression of p53 target genes and
      elicited both G1 and G2/M cell cycle arrest upon shift to the permissive
      temperature. Ectopic expression of the same ts p53 allele with two additional
      point mutations (Gln22, Ser23) that abolish p53-transcriptional activation did
      not induce p53 target genes and G1 nor G2/M cell cycle arrest. In HCT116 colon
      carcinoma cells ectopic expression of wild type p53 does not elicit apoptosis
      whereas p53 mutant deficient in trans-activation induces apoptosis. The ability
      of wild type p53 to induce apoptosis is restored in HCT116 cells that are null
      for p21. However, the trans-activation deficient mutant of p53 is still more
      potent mediator of apoptosis than wild type p53 in the p21 null cells. Although
      the ability of Gln22,Ser23 to trans-activate p53 target genes is diminished, it
      retains the ability to repress Bcl-2 expression. Thus, we conclude that while
      ectopic expression of wild type p53 can induce both G1 and G2/M arrest, in a p21
      dependent manner, without apoptosis, a p53 mutant defective in trans-activation
      elicits apoptosis without inducing cell cycle arrest. Further, the anti-apoptotic
      function of p53 is dependent on trans-activation and is linked to cell cycle
      arrest. The results strongly suggest that the trans-activation deficient mutant
      is a more potent inducer of apoptosis because it lost its anti-apoptotic function
      and retains its ability to repress pro-apoptotic genes such as Bcl-2. Taken
      together, the results imply that employing a trans-activation deficient p53 in
      gene therapy approaches or the use of drugs that convert mutant p53 to a trans
      activation-independent mediator of apoptosis may be much more efficient
      therapeutic approaches than current approaches that employ wild type p53.

PMID- 11314000
TI  - A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not
      NF-kappaB or ODC transactivation.
AB  - Pdcd4 is a novel transformation suppressor that is highly expressed in promotion
      resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells.
      Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells
      resistant to tumor promoter-induced transformation, indicating that elevated
      expression of Pdcd4 protein is sufficient to suppress neoplastic transformation.
      To determine whether Pdcd4 suppresses neoplastic transformation through
      inhibiting known transformation required events, we examined the possibility that
      pdcd4 inhibited the activation of AP-1 or NF-kappaB dependent transcription or of
      ornithine decarboxylase (ODC) activity. Activation of AP-1-dependent
      transcriptional activity was inhibited by pdcd4 expression in a concentration
      dependent manner. In contrast, Pdcd4 slightly increased NF-kappaB-dependent
      transcription and did not alter ODC enzymatic activity. Previous studies
      suggested that activation of AP-1 was required for P+ cell transformation as well
      as for tumor promotion in vivo. These results indicate that Pdcd4 functions as a
      transformation suppressor, possibly through inhibiting AP-1 activation in
      combination with other factors such as enhancing NF-kappaB activation. Pdcd4 may
      thus constitute a useful molecular target for cancer prevention.

PMID- 11314001
TI  - The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention
      of apoptosis of Hep3B cells by interleukin-6.
AB  - Interleukin-6 (IL-6) is a pleitrophic cytokine that not only regulates growth and
      differentiation of many cell types, but also induces production of acute phase
      proteins (AAP) in hepatocytes. Our previous works have demonstrated that both PI
      3-K/Akt and STAT3 pathways were concomitantly activated and cooperatively
      mediated the anti-apoptotic effect of IL-6. This investigation reports that IL-6
      protected cells against apoptosis induced by a variety of agents including, TGF
      beta, UV and retinoic acid (RA) in Hep3B cells, suggesting that IL-6 is a
      fundamental determinant of hepatic cell survival. Mcl-1, but not other Bcl-2
      family members, was rapidly up-regulated by IL-6, with a peak (approximately 3-4
      fold) appearing at 4 h. Transient transfection of cells with a mcl-1 antisense
      vector, resulting in a 50-60% reduction of the anti-apoptotic effect of IL-6,
      indicating that Mcl-1 is a downstream effector of IL-6. Which signaling pathway
      transduced by IL-6 responsible for the Mcl-1 up-regulation was further
      investigated. In Hep3B cells, the JAK/STAT3, ERK, and PI 3-K/Akt pathways were
      activated by IL-6 stimulation. Blocking JAK/STAT3 activation with a dominant
      negative mutant STAT3F or a JAK inhibitor AG490 could not influence IL-6-mediated
      Mcl-1 up-regulation. Similarly, PD98059 treatment, a MEK specific inhibitor, also
      failed to inhibit Mcl-1 expression. However, the IL-6-induced Mcl-1 up-regulation
      was effectively attenuated in the presence of PI 3-K inhibitors, LY294002 and
      wortmannin. Expression of dominant-negative Akt, but not Etk, could abrogate the
      IL-6-induced increase of Mcl-1. In conclusion, our results suggest that the anti
      apoptotic effect of IL-6 is mediated, at least in part, by Mcl-1 expression and
      that is mainly through the PI 3-K/ Akt-dependent pathway.

PMID- 11314002
TI  - Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell
      carcinoma.
AB  - 4p16.3 has previously been identified as a region of non-random LOH in
      transitional cell carcinoma, suggesting the presence of a tumour suppressor gene.
      One candidate within this region is fibroblast growth factor receptor 3 (FGFR3).
      Germline mutations in FGFR3 are known to cause several autosomal dominant
      skeletal dysplasias, the severity of which depends on the position and nature of
      the mutation in the protein. We investigated the frequency and nature of FGFR3
      mutations in a panel of transitional cell carcinomas and cell lines and studied
      the possible link between mutation and loss of heterozygosity (LOH) on 4p16.3.
      FGFR3 coding sequence from 63 transitional cell carcinomas (TCC) of various
      stages and grades, and 18 cell lines was analysed by fluorescent SSCP. Samples
      with abnormal migration patterns were sequenced to identify the mutation or
      polymorphism. Thirty-one of the 63 tumours had previously been assessed to have
      LOH at 4p16.3. Twenty-six of the 63 tumours (41%) and 4/18 (22%) of the cell
      lines had missense mutations in FGFR3. All mutations detected in our panel have
      been reported in the germline where all apart from one cause lethal conditions.
      One tumour contained K652Q which has recently been identified in less severe
      cases of skeletal dysplasia. Tumours with and without LOH at 4p16.3 had mutations
      in FGFR3 suggesting that these two events are not causally linked. The frequency
      of FGFR3 mutation indicates that this protein plays an important role in TCC.

PMID- 11314003
TI  - A single Glu(62)-to-Lys(62) mutation in the Mos residues of the R7Delta447Gag
      tMos protein causes the mutant virus to induce brain lesions.
AB  - We previously reported that R7Delta447, a 2954-base-pair (bp) laboratory
      generated Moloney murine sarcoma virus, induced subcutaneous tumors in about 14%
      of infected mice but did not induce brain lesions. We now report that
      R7Delta447K, a spontaneous mutant of R7Delta447, induced brain lesions as well as
      subcutaneous tumors in all injected mice. The genomes of the two viruses differ
      in a single base pair: the deduced Glu(62) of the Mos residue of the R7Delta447
      Gag-tMos protein is changed to Lys(62). More R7Delta447 than R7Delta447K focus
      forming units were detected in both NIH3T3 and mouse cerebral vascular
      endothelial (MCVE) cells. However, R7Delta447K transformed NIH3T3 and MCVE cells
      more acutely than did R7Delta447. A distinctive feature that distinguished the
      morphologic transformation of R7Delta447- and R7Delta447K-infected MCVE cells is
      the markedly prolonged spindle-shaped phase exhibited by R7Delta447-infected MCVE
      cells. In addition, R7Delta447K was more efficient in inducing the
      phosphorylation of ERK1/2 than R7Delta447 in both MCVE and NIH3T3 cells. Moreover
      morphologic transformation was inhibited, and levels of phosphorylated ERK1/2
      were reduced when R7Delta447- or R7Delta447K-infected NIH3T3 or MCVE cells were
      grown in the presence of the MEK1/2-specific inhibitor PD98095. Thus, we have
      identified a key residue in the Gag-tMos protein that profoundly affects
      activation of the Mos/MEK/ERK pathway, virus and cell replication, morphologic
      transformation in vitro and pathogenicity in vivo.

PMID- 11314004
TI  - Mcl-1, an early-induction molecule, modulates activin A-induced apoptosis and
      differentiation of CML cells.
AB  - Activin A, one member of the transforming growth factor (TGF)-beta superfamily,
      is known to be a commitment factor for cell death and differentiation. In the
      present study, we demonstrate that human chronic myeloid leukemia (CML) cell
      lines, KU812 and K562 cells, either induced apoptosis or differentiation,
      respectively, by treatment with activin A. During these cell fate decisive events
      caused by activin A, rapid and transient up-regulation of Mcl-1 was observed in
      both cell lines. In activin A-induced apoptosis of KU812 cells, continuous up
      regulation of Bax was observed. After the decrease in Mcl-1 expression had
      occurred, activation of caspase-9 and caspase-3 and cleavage of DFF45 were shown
      to take place in KU812 cells, resulting in the fragmentation of the genomic DNA
      of the cells. In contrast, the down-regulation of Mcl-1 without up-regulation of
      Bax caused accumulation of hemoglobin (Hb) contents in activin A-treated K562
      cells. Interestingly, erythropoietin (EPO) prevented activin A-induced apoptosis
      with continuous expression of Mcl-1 and caused KU812 cells to undergo erythroid
      differentiation. To address the role of Mcl-1 in activin A-treated CML cells,
      KU812 and K562 cells were stably transfected with cDNA encoding Mcl-1 (designated
      as KU812/mcl and K562/mcl cells). As in combined effect of activin A and EPO on
      the parental KU812 cells, activin A induced differentiation, but not apoptosis,
      of KU812/mcl cells without modulating Bax levels. Activin A-treated K562/mcl
      cells, as well as parental cells, were only differentiated to erythroid cells.
      These results suggest that Mcl-1 is an early inducible gene activated by the
      activin A signaling pathway for both cellular differentiation and apoptosis, and
      continuous expression of Mcl-1 may be contributed to differentiation signals to
      the erythroid lineage in CML cells.

PMID- 11314005
TI  - Expression of mutant telomerase in immortal telomerase-negative human cells
      results in cell cycle deregulation, nuclear and chromosomal abnormalities and
      rapid loss of viability.
AB  - We have reconstituted wild type or mutant telomerase activity in two human cell
      lines that lack constitutive expression of both core subunits of the enzyme and
      maintain telomeres by a telomerase-independent mechanism (ALT cells). Wild type
      telomerase RNA and four telomerase RNAs with single point mutations in their
      template domain were used to express enzymes specifying different telomeric DNA
      sequences. Expression of wild type telomerase for up to 32 days had no detectable
      effect on cell growth or viability. In contrast, cells expressing mutant
      telomerases had slower growth rate, abnormal cell cycle and reduced viability.
      Dramatically aberrant nuclei, typical of cells undergoing mitotic catastrophe,
      and large numbers of fused chromosomes were also characteristic of these
      populations. Notably, all phenotypes were apparent within the first few cell
      divisions after expression of the enzymes. Unlike wild type, mutant telomerase
      activity was progressively selected against with cell culturing, and this
      correlated with the disappearance of cells with aberrant phenotypes. Our results
      suggest that even very limited synthesis of mutated sequences can affect telomere
      structure in human cells, and that the toxicity of mutant telomerases is due to
      telomere malfunction.

PMID- 11314006
TI  - A translationally regulated Tousled kinase phosphorylates histone H3 and confers
      radioresistance when overexpressed.
AB  - The gene Tousled of Arabidopsis Thaliana encodes a protein kinase which, when
      mutated, results in abnormal flower development. From a library of mRNAs that are
      translationally upregulated by overexpression of the translation initiation
      factor 4E, we identified a mammalian Tousled Like kinase (TLK1B). The human TLK1B
      mRNA contains a 5'UTR 1088-nt-long with two upstream AUG codons, and was found to
      be very inhibitory for translation. The TLK1B protein localizes almost
      exclusively to the nuclei. TLK1B overexpression in mammalian cells rendered them
      more resistant to ionizing radiation (IR). Purified TLK1B phosphorylated histone
      H3 at S(10) with high specificity both in a mix of core histones and in isolated
      chromatin, suggesting that histone H3 is a physiological substrate for TLK1B.
      Moreover, overexpression of TLK1B in transfected cells resulted in a higher
      degree of H3 phosphorylation. Expression of TLK1B in a yeast strain that harbors
      a temperature-sensitive mutation of the major H3 kinase, Ipl1, complemented the
      growth defect; restored normal levels of histone H3 phosphorylation; and
      increased their resistance to IR. Phosphorylation of H3 has been linked to the
      activation of the immediate-early genes upon mitogenic stimulation, and to
      chromatin condensation during mitotic/meiotic events. A possible role for TLK1B
      in radioprotection is discussed.

PMID- 11314007
TI  - Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder
      human tumor biopsies.
AB  - The Ku70/80 heterodimer is the regulatory subunit of the DNA-dependent protein
      kinase (DNA-PK) and its DNA-binding activity mediates DNA double-strand breaks
      repair. Although Ku80 was recently proposed as a caretaker gene involved in the
      control of genome integrity, no data are available on Ku70/80 DNA-binding
      activity in human tumors. Heterodimer DNA-binding activity and protein expression
      were assayed by electrophoretic-mobility-shift-assay (EMSA) and Western blot
      analysis, in nuclear and cytoplasmic extracts from eight breast, seven bladder
      primary tumors and three metastatic nodes from breast cancers. Corresponding
      normal tissues of the same patients were used as controls. Ten out of 15 tumors
      showed nuclear Ku-binding activity 3-10 times higher than in the normal tissues,
      irrespective of bladder or breast origin. Conversely, in 5/15 primary tumors and
      in all the metastatic nodes analysed, nuclear Ku-activity was 1.5-4.5-fold lower
      than in the corresponding normal tissues. Cytoplasmic heterodimer activity
      significantly differed between tumor and normal tissues, displaying a 2-10-fold
      increase in neoplastic tissues. Three different patterns combining both Ku
      expression and activity with tumor characteristics were identified. In low
      aggressive breast tumors p70/p80 proteins were expressed in tumor but not in
      normal tissues. The heterodimer binding-activity matched the protein levels. In
      non-invasive bladder carcinomas no significant differences in protein expression
      between tumor and the corresponding normal tissues were found, however
      heterodimer binding-activity was increased in tumor samples. In breast and
      bladder tumors, at the advanced stage and in node metastases, the binding
      activity was strongly reduced in tumor biopsies, however no differences were
      demonstrated between normal and tumor protein levels. Our results suggest a
      different modulation of Ku70/80 DNA-binding activity in human neoplastic tissues,
      possibly related to tumor progression. Findings provide further data on tissue
      specific protein expression and post-translational regulation of heterodimer
      activity.

PMID- 11314008
TI  - Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a
      naturally-occurring model for human cancer.
AB  - Homologues for human p53 (Hsp53) and p73 (Hsp73) genes were cloned and expression
      patterns for their corresponding proteins analysed in tissues from normal and
      leukemic softshell clams (Mya arenaria). These are the first structural and
      functional data for p53 and p73 cDNAs and gene products in a naturally occurring,
      non-mammalian disease model. Core sequence of the predicted clam p53 (Map53) and
      p73 (Map73) proteins is virtually identical and includes the following highly
      conserved regions: the transcriptional activation domain (TAD), MDM2 binding
      site, ATM phosphorylation site, proline rich domain, DNA binding domains (DBDs)
      II-V, nuclear import and export signals and the tetramerization domain. The core
      sequence is a structural mosaic of the corresponding human proteins, with the TAD
      and DBDs resembling Hsp53 and Hsp73, respectively. This suggests that Map53 and
      Map73 proteins may function similarly to human proteins. Clam proteins have
      either a short (Map53) or long (Map73) C-terminal extension. These features
      suggest that Map53 and Map73 may be alternate splice variants of a p63/p73-like
      ancestral gene. Map73 is significantly upregulated in hemocytes and adductor
      muscle from leukemic clams. In leukemic hemocytes, both proteins are absent from
      the nucleus and sequestered in the cytoplasm. This observation suggests that a
      non-mutational p53/p73-dependent mechanism may be involved in the clam disease.
      Further studies of these gene products in clams may reveal p53/p73-related
      molecular mechanisms that are held in common with Burkitt's lymphoma or other
      human cancers.

PMID- 11314009
TI  - Regulation of the expression of c-Myc by beta1 integrins in epithelial cells.
AB  - Cell adhesion promotes cellular proliferation through the regulation of gene
      expression, including the immediate early genes. However, the precise role of
      cell adhesion in the regulation of the c-Myc proto-oncogene is not clear, and the
      adhesion-dependent signaling pathway(s) regulating the expression of c-Myc has
      yet to be defined. We now show that integrin signaling directly regulates the
      expression of c-Myc in the mammary epithelial cell line 184A1N4 (A1N4). Adhesion
      of quiescent A1N4 cells to fibronectin, and to collagen types IV or I, induces
      the expression of c-Myc in an ECM concentration-dependent fashion. Cytoskeletal
      rearrangement, and integrin engagement and integrin clustering are required for
      the induction of c-Myc by fibronectin. Furthermore, beta1 integrin function
      blocking antibodies prevent the adhesion-dependent induction of c-Myc. Adhesion
      of A1N4 cells results in the activation both of c-Src and of the Erk 1/2 mitogen
      activated protein kinase (MAPK), each of which precedes the induction of c-Myc.
      Pharmacological inhibitors specific for either the c-Src family of kinases or for
      MEK1 block the adhesion-dependent induction of c-Myc. These observations indicate
      that beta1 integrins regulate the expression of c-Myc through the activation of
      the Src family of tyrosine kinases and the MAK kinase pathway.

PMID- 11314010
TI  - p73 is transcriptionally regulated by DNA damage, p53, and p73.
AB  - p73 is a member of the p53 family. Recent studies have shown that DNA damage can
      stabilize p73 protein and enhance p73-mediated apoptosis in a c-Abl dependent
      manner. To determine what regulates p73 transcriptionally, we analysed the
      expression of p73 in several cell lines following genotoxic stresses. We found
      that p73 is induced in certain cell lines when treated with therapeutic DNA
      damaging agents. We also found that p53 and p73, but not mutant p53(R249S) and
      p73beta292, directly induce the expression of the p73 gene. In addition, we found
      one potential p53-binding site in the promoter of the p73 gene. This binding site
      is responsive to p53, p73, and DNA damage. Taken together, these data suggest
      that p73 is transcriptionally regulated by DNA damage and p53, and is
      autoregulated.

PMID- 11314011
TI  - Human ARF protein interacts with topoisomerase I and stimulates its activity.
AB  - The ARF gene (p19(ARF) in mouse and p14(ARF) in man) has become a central actor
      of the cell cycle regulation process as it participates to the ARF-MDM2-p53
      pathway and the Rb-E2F-1 pathway. By use of immunoprecipitation and Western
      blotting (IP/WB), we now show that ARF physically associates with topoisomerase I
      (Topo I). ARF-Topo I immune complexes were detected in SF9 insect cells infected
      with recombinant baculoviruses encoding the two genes as well as in 293 cells
      that express endogenously these proteins. Preparations of a GST-ARF recombinant
      protein stimulated the DNA relaxation activity of Topo I but, in contrast, had no
      effect on the decatenation activity of Topo II. The Topo I stimulation was also
      detected in cell extracts of SF9 cells expressing both proteins. A confocal
      microscopy study indicated that part of ARF and Topo I colocalized in the
      granular component structure of the nucleolus. As a whole, our data indicate that
      Topo I is a new partner of ARF and suggest that ARF is involved in cell reactions
      that require Topo I.

PMID- 11314012
TI  - The v-ErbA oncoprotein quenches the activity of an erythroid-specific enhancer.
AB  - v-ErbA is a mutated variant of thyroid hormone receptor (TRalpha/NR1A1) borne by
      the Avian Erythroblastosis virus causing erythroleukemia. TRalpha is known to
      activate transcription of specific genes in the presence of its cognate ligand,
      T3 hormone, while in its absence it represses it. v-ErbA is unable to bind
      ligand, and hence is thought to contribute to leukemogenesis by actively
      repressing erythroid-specific genes such as the carbonic anhydrase II gene (CA
      II). In the prevailing model, v-ErbA occludes liganded TR from binding to its
      cognate elements and constitutively interacts with the corepressors NCoR/SMRT. We
      previously identified a v-ErbA responsive element (VRE) within a DNase I
      hypersensitive region (HS2) located in the second intron of the CA II gene. We
      now show that HS2 fulfils all the requirements for a genuine enhancer that
      functions independent of its orientation and position with a profound erythroid
      specific activity in normal erythroid progenitors (T2ECs) and in leukemic
      erythroid cell lines. We find that the HS2 enhancer activity is governed by two
      adjacent GATA-factor binding sites. v-ErbA as well as unliganded TR prevent HS2
      activity by nullifying the positive function of factors bound to GATA-sites.
      However, v-ErbA, in contrast to TR, does not convey active repression to silence
      the transcriptional activity intrinsic to a heterologous tk promoter. We propose
      that depending on the sequence and context of the binding site, v-ErbA
      contributes to leukemogenesis by occluding liganded TR as well as unliganded TR
      thereby preventing activation or repression, respectively.

PMID- 11314013
TI  - Distinct tyrosine autophosphorylation sites mediate induction of epithelial
      mesenchymal like transition by an activated ErbB-2/Neu receptor.
AB  - Tight control of cell proliferation and morphogenesis is required to ensure
      normal tissue patterning and prevent cancer formation. Overexpression of the ErbB
      2/Neu receptor tyrosine kinase is associated with increased progression in human
      breast cancer, yet in breast explant cultures, the ErbB-2/Neu receptor
      contributes to alveolar differentiation. To examine the consequence of
      deregulated ErbB-2/Neu activation on epithelial morphogenesis, we have expressed
      a constitutively activated mutant of ErbB-2/Neu in a Madin-Darby canine kidney
      (MDCK) epithelial cell model. Using two-dimensional cultures we demonstrate that
      activated ErbB-2/Neu induces breakdown of cell-cell junctions, increased cell
      motility and dispersal of epithelial colonies. This correlates with
      reorganization of the actin cytoskeleton and focal adhesions and loss of
      insoluble cell-cell junction complexes involving E-cadherin. Interestingly, a
      constitutively activated ErbB-2/Neu receptor promotes an invasive morphogenic
      program in MDCK cells in a three-dimensional matrix. We show that two tyrosines
      in the carboxy-terminal tail of ErbB-2/Neu, involved in the phosphorylation of
      the Shc adapter protein, are each sufficient to promote epithelial-mesenchymal
      like transition and enhanced cell motility in two-dimensional culture and cell
      invasion rather than a morphogenic response in matrix culture. This provides a
      model system to investigate ErbB-2/Neu induced signaling pathways required for
      epithelial cell dispersal and invasion versus morphogenesis.

PMID- 11314014
TI  - HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF
      3 recruitment of the CBP/p300 coactivators.
AB  - Human herpes virus 8 (HHV-8) has developed unique mechanisms for altering
      cellular proliferative and apoptotic control pathways by incorporating viral
      homologs to several cellular regulatory genes into its genome. One of the
      important pirated genes encoded by the ORF K9 reading frame is a viral homolog of
      the interferon regulatory factors (IRF), a family of cellular transcription
      proteins that regulates expression of genes involved in pathogen response, immune
      modulation and cell proliferation. vIRF-1 has been shown to downregulate the
      interferon- and IRF-mediated transcriptional activation of ISG and murine IFNA4
      gene promoters. In this study we demonstrate that vIRF-1 efficiently inhibited
      virus-induced expression of endogenous interferon B, CC chemokine RANTES and CXC
      chemokine IP-10 genes. Co-expression analysis revealed that vIRF-1 selectively
      blocked IRF-3 but not IRF-7-mediated transactivation. vIRF-1 was able to bind to
      both IRF-3 and IRF-7 in vivo as detected by coimmunoprecipitation analysis, but
      did not affect IRF-3 dimerization, nuclear translocation and DNA binding
      activity. Rather, vIRF-1 interacted with the CBP/p300 coactivators and
      efficiently inhibited the formation of transcriptionally competent IRF-3-CBP/p300
      complexes. These results illustrate that vIRF-1 is able to block the early stages
      of the IFN response to virus infection by interfering with the activation of IRF
      3 responsive, immediate early IFN genes.

PMID- 11314015
TI  - p53-dependent radiation-induced crypt intestinal epithelial cells apoptosis is
      mediated in part through TNF-TNFR1 system.
AB  - Radiation induces apoptosis of crypt intestinal epithelial cells (IEC) through a
      pathway that is largely dependent on p53. However, exactly how p53 mediates IEC
      apoptosis is unclear. Studies in vitro suggest that one mechanism by which p53
      mediates apoptosis is through its ability to transactivate members of the TNF
      receptor family of 'Death Receptors'. Here, we examined the role of one of its
      member, TNF receptor type 1 (TNFR1), in an in vivo model of p53-dependent
      radiation-induced IEC apoptosis. We demonstrate that mice genetically engineered
      to be deficient in TNF receptor type 1 (TNFR1(-/-)) and mice injected with TNFR1
      fusion chimeric protein (TNFR1-Fc; a competitive inhibitor of TNFR1) were
      partially protected (30-40%) from p53-dependent radiation-induced IEC apoptosis.
      However, we found no evidence to support the possibility p53 transcriptionally
      regulates the expression of TNFR1 nor increases the susceptibility of IEC to TNF
      mediated apoptosis. Interestingly, we found that injection of TNF readily induced
      IEC apoptosis and that radiation induced a p53-dependent increase in the
      intestinal level of TNF. Furthermore, injection of a neutralizing anti-TNF mAb
      reduced p53-dependent radiation-induced IEC apoptosis by approximately 60%.
      Overall, these results suggest that p53-dependent radiation-induced IEC apoptosis
      is mediated in part through ability of p53 to regulate TNF, which subsequently
      induces IEC apoptosis through TNFR1.

PMID- 11314016
TI  - NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of
      human colonic adenomatous polyps.
AB  - The factors that govern the progression from colonic adenomatous polyp to colon
      cancer are poorly understood. The observation that NSAIDs act as
      chemopreventative agents and reduce the size of colonic polyps suggests the
      involvement of inflammatory signalling, but inflammatory signalling in colonic
      polyps has not been studied. We investigated the expression of the active forms
      of NF-kappaB, JNK and p38 MAPK using immunohistochemistry with activation
      specific antibodies in human colonic adenomas. We show that active NF-kappaB is
      seen in stromal macrophages that also express COX-2 and TNF-alpha, active JNK is
      seen in stromal and intraepithelial T-lymphocytes and periendothelial cells of
      new blood vessels, and active p38 MAPK is most highly expressed in macrophages
      and other stromal cells. These results demonstrate the presence of active
      inflammatory signal transduction in colonic polyps and that these are
      predominantly in the stroma. In the case of NF-kappaB this coincides with the
      cellular localisation of COX-2. These results support evidence that NSAIDs may
      act through effects on stromal cells rather than epithelial cells.

PMID- 11314017
TI  - Functional evidence for a telomerase repressor gene on human chromosome 10p15.1.
AB  - Based on the sites of frequent allelic loss in hepatocellular carcinoma, five
      normal human chromosomes (2, 4, 5, 10 and 16) were transferred individually into
      a telomerase-positive human hepatocellular carcinoma cell line, Li7HM, by
      microcell-mediated chromosome transfer (MMCT). Chromosome 10, but not the others,
      repressed telomerase activity immediately and stopped cell growth after 50
      population doublings (PDs). Loss of the transferred 10p loci resulted in the
      emergence of revertant cells that continued to proliferate and expressed
      telomerase activity, suggesting the presence of a telomerase repressor gene on
      this chromosomal arm. Transfer of a series of defined fragments from chromosome
      10p successfully narrowed down the responsible region: a 28.9-cM region on 10p15
      (between WI-4752 and D10S249), but not a 26.2-cM region (between D10S1728 and
      D10S249), caused repression of telomerase activity and progressive telomere
      shortening. A strong correlation between the expression level of telomerase
      catalytic subunit gene (hTERT) and telomerase activity was observed. These
      findings suggest that a novel telomerase repressor gene which controls the
      expression of hTERT is located on the 2.7-cM region (between WI-4752 and
      D10S1728) on chromosome 10p15.1.

PMID- 11314018
TI  - The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response
      in Ba/F3 cells.
AB  - The leukemia-associated TEL-Jak2 fusion protein possesses a constitutive tyrosine
      kinase activity and transforming properties in hematopoietic cell lines and
      animal models. In the murine pro-B Ba/F3 cell line, this fusion constitutively
      activates the Signal Transducer and Activator of Transcription 5 (Stat5) factors
      and, as a consequence, induces the sustained expression of various Stat5-target
      genes including the Cytokine Inducible SH2-containing protein (Cis) gene, which
      codes for a member of the Suppressor of Cytokine Signaling (Socs) protein family.
      In TEL-Jak2-transformed Ba/F3 cells, we also observed the upregulation of the
      Socs1 gene, whose product has been reported to negatively regulate the Jak kinase
      activity. In transient transfection experiments, Socs1 physically interacts with
      TEL-Jak2 and interferes with the TEL-Jak2-induced phosphorylation and activation
      of Stat5 factors, probably through the Socs1-induced proteasome-mediated
      degradation of the fusion protein. Interestingly, TEL-Jak2-expressing Ba/F3 cells
      were found to be resistant to the anti-proliferative activities of gamma
      interferon (IFN-gamma) seemingly as a consequence of Socs1 constitutive
      expression. These results indicate that the Socs1-dependent cytokine feedback
      loop, although active, is bypassed by the TEL-Jak2 fusion, but may play a role in
      the leukemogenic process by altering the cytokine responses of the leukemic
      cells. Our results also suggest that Socs1 plays a role in shutting down the
      signaling from the normally activated Jak2 kinase by inducing its proteasome
      dependent degradation.

PMID- 11314019
TI  - Inhibition of NF-kappaB sensitizes human pancreatic carcinoma cells to apoptosis
      induced by etoposide (VP16) or doxorubicin.
AB  - The transcription factor NF-kappaB has anti-apoptotic properties and may confer
      chemoresistance to cancer cells. Here, we describe human pancreatic carcinoma
      cell lines that differ in the responsiveness to the topoisomerase-2 inhibitors
      VP16 (20 microM) and doxorubicin (0.3 microM): Highly sensitive T3M4 [corrected]
      and PT45-P1 cells, and Capan-1 and A818-4 cells that were almost resistant to
      both anti cancer drugs. VP16, but not doxorubicin, transiently induced NF-kappaB
      activity in all cell lines, whereas basal NF-kappaB binding was nearly
      undetectable in T3M4 [corrected] and PT45-P1 cells, but rather high in Capan-1
      and A818-4 cells, as demonstrated by gel-shift and luciferase assays. Treatment
      with various NF-kappaB inhibitors (Gliotoxin, MG132 and Sulfasalazine), or
      transfection with the IkappaBalpha super-repressor, strongly enhanced the
      apoptotic effects of VP16 or doxorubicin on resistant Capan-1 and 818-4 cells.
      Our results indicate that under certain conditions the resistance of pancreatic
      carcinoma cells to chemotherapy is due to their constitutive NF-kappaB activity
      rather than the transient induction of NF-kappaB by some anti-cancer drugs.
      Blockade of basal NF-kappaB activity by well established drugs efficiently
      reduces chemoresistance of pancreatic cancer cells and offers the potential for
      improved therapeutic strategies.

PMID- 11314020
TI  - Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1.
AB  - Alpha-fetoprotein (AFP) producing gastric cancer (AFP-GC) is very malignant and
      highly metastatic compared with common gastric cancer. However, the causal
      relationship between AFP production and the high malignancy of AFP-GC is unclear.
      We investigated AFP gene regulation in AFP-GC by an active transcription factor,
      HNF1 (hepatocyte nuclear factor 1) and a repressive transcription factor, ATBF1
      (AT motif binding factor 1). RNase protection assays revealed that the production
      of AFP in gastric cancer cells did not directly associate with HNF1 expression.
      An inverse relation between the expressions of ATBF1 and AFP was clearly observed
      in gastric cancer cells. CAT assays showed the direct inhibition of AFP gene
      expression by ATBF1. Methylation analysis of the AFP promoter region in gastric
      cancer cells suggested that methylation itself could not explain the silencing of
      the AFP gene. Immunohistochemistry of resected clinical samples revealed that AFP
      producing cells lacked ATBF1 immunoreactivity. Our data suggests that the absence
      of ATBF1 is responsible for AFP gene expression in gastric cancer, and the
      absence of ATBF1 is a distinct characteristic of AFP-GC and might be important
      for its highly malignant nature.

PMID- 11314021
TI  - Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4 : 11)
      abnormality.
AB  - Rearrangements of the human ALL-1 gene are frequently encountered in acute
      lymphocytic leukemias (ALL) and acute myeloid leukemias (AML). These
      rearrangements are mostly due to chromosome translocations and result in
      production of chimeric proteins composed of the N-terminal fragment of ALL-1 and
      the C-terminal segments of the partner proteins. The most common chromosome
      translocation involving ALL-1 is the t(4 : 11) associated with ALL. ALL-1 is the
      human homologue of Drosophila trithorax and directly activates transcription of
      multiple Hox genes. A preliminary DNA microarray screen indicated that the Meis1,
      HoxA9 and AC133 genes were overexpressed in ALLs with t(4 : 11), compared to ALLs
      with very similar phenotype but without the chromosomal abnormality. These genes,
      as well as additional five Hox genes, were subjected to comprehensive semi
      quantitative or quantitative RT-PCR analysis in 57 primary ALL and AML tumors.
      Meis1 and HoxA9 were found expressed in 13/14 of ALLs with the t(4 : 11) and in
      8/8 of AMLs with ALL-1 rearrangements. The two genes were not consistently
      transcribed in other types of ALL. AC133 was transcribed in 13/14 of ALLs with
      t(4 : 11), but in only 4/8 of AMLs with ALL-1 rearrangements. HoxA10 was
      expressed in most leukemias with ALL-1 alterations, but was also transcribed in
      PrePreB CD10(-) ALLs lacking the t(4 : 11). Expression of HoxA5, HoxA7, HoxC8 and
      HoxC10 did not correlate with ALL-1 rearrangements. Coexpression of Meis1 and
      HoxA9, overexpression of HoxA10, and overexpression or fusion of HoxA9 were
      previously implicated in certain acute myeloid leukemias in mice and humans. The
      present work suggests that upregulation of Meis1, HoxA9, and possibly HoxA10
      might also play a role in pathogenesis of acute lymphocytic and acute myeloid
      leukemias associated with ALL-1 fusions.

PMID- 11314022
TI  - Smad7 inhibits the survival nuclear factor kappaB and potentiates apoptosis in
      epithelial cells.
AB  - In this study, we examined the effect of the stable expression of Smad7 in two
      different cell lines on apoptosis induced by various stimuli including TGF-beta,
      serum withdrawal, loss of cell adhesion (anoikis) and TNF-alpha. Smad7 increased
      TGF-beta-mediated apoptosis in Mv1Lu cells as well as anoikis and/or serum
      withdrawal-induced apoptosis in Mv1Lu and MDCK cells. Smad7 markedly decreased
      the activity of the survival NF-kappaB transcription factor in MDCK cells.
      Interestingly, the stable expression of oncogenic Ras in MDCK cells which
      suppressed Smad7 inhibition of NF-kappaB also suppressed Smad7 potentiation of
      serum withdrawal-induced apoptosis and anoikis. In addition, Smad7 inhibited TNF
      alpha stimulation of NF-kappaB and increased TNF-alpha-mediated apoptosis in MDCK
      cells. Our results provide the first evidence that Smad7 induces sensitization of
      cells to different forms of cell death. They moreover demonstrate that Smad7
      inhibits the survival NF-kappaB factor, providing a potential mechanism whereby
      Smad7 potentiates cell death.

PMID- 11314023
TI  - Expression and alternative splicing of c-ret RNA in papillary thyroid carcinomas.
AB  - Somatic rearrangements of the ret receptor tyrosine kinase have been consistently
      reported in papillary thyroid carcinomas (PTC). It is unclear whether the
      expression of wild-type c-ret may also be implicated in thyroid tumorigenesis. We
      studied ret mRNA expression in PTC from Norwegian patients. Using RT-PCR, wild
      type ret mRNA was detected in all of 22 PTC and in a PTC cell line. c-ret mRNA
      was clearly overexpressed in PTC as compared to non-neoplastic thyroid tissue.
      Hybridization using ret exon DNA dot blot arrays and complex cDNA probes
      confirmed expression of ret RNA in thyroid biopsies. In accordance with the RNA
      data, Western immunoblotting showed evidence of wild-type Ret protein in PTC.
      Rearrangements generating the ret/PTC oncogenes co-existed with c-ret mRNA in
      PTC. Multiple alternative ret splicing variants were detected in PTC. Four novel
      ret splicing events were found in the region encoding the extracellular domain.
      The open reading frames of these transcripts were all in-frame with the Ret
      tyrosine kinase domain. In the central ret mRNA region encoding the cysteine
      rich, transmembrane, and main tyrosine kinase domains, no evidence of alternative
      splicing was detected. Two alternative splice events were detected in the ret
      mRNA encoding the C-terminal part of Ret protein harboring tyrosine residues
      important for Ret signaling, excluding exon 19, or retaining intron 19,
      respectively. Ribonuclease protection assays confirmed the presence of ret
      alternative splicing events in thyroid biopsies. We conclude that in addition to
      ret/PTC rearrangements, wild-type c-ret mRNA and alternatively spliced ret
      transcripts are present in PTC. Transcriptional up-regulation and post
      transcriptional mechanisms of c-ret RNA processing may contribute to differences
      in expression of Ret protein observed in PTC compared to non-neoplastic thyroid
      tissue.

PMID- 11314024
TI  - An internal ribosome entry segment in the 5' untranslated region of the mnt gene.
AB  - Mnt is a transcriptional repressor related to the Myc/Mad family of transcription
      factors. It is expressed in proliferating, resting and differentiating cells and
      is believed to antagonize the function of Myc. Here we have characterized the
      major transcription initiation site of the mnt gene. In doing so we noted a
      remarkable level of sequence conservation between the murine and human 5'
      untranslated regions. Our experiments revealed that this sequence contains an
      internal ribosome entry segment (IRES). In addition, we show that sequences at
      both the 5' and 3' end of the IRES are essential for its function. These findings
      indicate that mnt can be translated by internal initiation. Such a mechanism may
      allow efficient Mnt synthesis when cap-dependent translation initiation is
      reduced.

PMID- 11314025
TI  - p53 activation in response to microtubule disruption is mediated by integrin-Erk
      signaling.
AB  - The p53 tumor suppressor is activated in response to various stresses driving the
      cells into growth arrest or apoptosis. We have addressed the question of how
      disintegration of microtubule system induces activation of p53. Depolymerization
      of microtubules by colcemid in rat and human quiescent fibroblasts resulted in
      accumulation of transcriptionally active p53 that caused cell-cycle arrest at the
      G1/S boundary. The p53 activation correlated with prominent activation of Erk1/2
      MAP kinases that resulted from colcemid-stimulated development of focal
      adhesions. Inhibition of focal contacts development by plating of cells onto poly
      L-lysine abrogated both Erk1/2 and p53 activations in colcemid-treated cells,
      while plating of cells onto fibronectin caused transient up-regulation of p53
      even in the absence of colcemid. Pre-treatment of cells with the specific MEK1
      inhibitor PD098059 also attenuated colcemid-induced p53 activation and G1 cell
      cycle arrest. Cell types which either failed to develop focal adhesions in
      response to colcemid treatment (human MCF-7 epithelial cells), or lacked colcemid
      induced sustained Erk activation (primary mouse embryo fibroblasts and 12(1)
      cells) showed virtually no p53 up-regulation in response to disruption of
      microtubules during G0/G1. Our results indicate that p53 activation is not
      triggered by disintegration of microtubule system by itself, but rather
      originates from some of the consequences of such disintegration, in particular,
      from the development of focal adhesions leading to activation of Erk signaling
      pathway.

PMID- 11314026
TI  - E2F-1 induces the stabilization of p53 but blocks p53-mediated transactivation.
AB  - E2F-1 induces p53 accumulation and E2F-1 and p53 form a physical complex, which
      affects the ability of E2F-1 to activate transcription. We mapped the domains on
      E2F-1 that interact with p53 and found two p53-binding domains. To understand the
      functional consequences of the E2F-1/p53 association on p53 activities we
      identified the domains of E2F-1 that were responsible for the accumulation of
      p53. Unexpectedly, we found that the E2F-1 transactivation domain was dispensable
      for p53 induction. By contrast, further deletion of the DP-1 interaction/'marked'
      box domain eliminated p53 accumulation. Radiolabeling pulse/chase analysis
      demonstrated that E2F-1 caused post-translational stabilization of p53. Although
      E2F-1 caused the stabilization of p53, E2F-1 expression impaired p53-dependent
      transactivation. Thus, the E2F-1 : p53 interaction may provide a checkpoint
      function to inactivate overactive E2F-1, but the association may also inactivate
      p53 transactivation to allow cell cycle progression.

PMID- 11314027
TI  - Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells
      independently of ATM/ATR.
AB  - Cyclin A/cdk2 is active during S and G2 phases of the cell cycle, but its
      regulation and function during G2 phase is poorly understood. In this study we
      have examined the regulation of cyclin A/cdk2 activity during normal G2 phase
      progression and in genotoxin-induced G2 arrest. We show that cyclin A/cdk2 is
      activated in early G2 phase by a cdc25 activity. In the G2 phase checkpoint
      arrest initiated in response to various forms of DNA damage, the cdc25-dependent
      activation of both cyclin A/cdk2 and cyclin B1/cdc2 is blocked. Ectopic
      expression of cdc25B, but not cdc25C, in G2 phase arrested cells efficiently
      activated both cyclin A/cdk2 and cyclin B1/cdc2. Finally, we demonstrate that the
      block in cyclin A/cdk2 activation in the G2 checkpoint arrest is independent of
      ATM/ATR. We speculate that the ATM/ATR-independent block in G2 phase cyclin
      A/cdk2 activation may act as a further layer of checkpoint control, and that
      blocking G2 phase cyclin A/cdk2 activation contributes to the G2 phase checkpoint
      arrest.

PMID- 11314028
TI  - Evidence for a role of the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase in
      thapsigargin and Bcl-2 induced changes in Xenopus laevis oocyte maturation.
AB  - Thapsigargin (Tg), a selective inhibitor of sarcoplasmic/endoplasmic reticulum
      Ca(2+)-ATPase (SERCA), causes depletion of intracellular Ca(2+) stores, hence
      activation of capacitative Ca(2+) entry (CCE). Incubation of Xenopus laevis
      oocytes with Tg resulted in an increased rate of progesterone-induced meiotic
      maturation. Non-mitochondrial (45)Ca(2+) uptake by SERCA-containing microsomes
      prepared from control wild-type oocytes microinjected with sterile water was
      inhibited essentially 100% by Tg. However, overexpression of Bcl-2, an oncogene
      known to protect against Tg-induced apoptosis in certain cell types, resulted in
      only 40% inhibition of microsomal (45)Ca(2+) uptake by Tg while non-inhibited
      (45)Ca(2+) uptake remained unchanged. Moreover Bcl-2 overexpression also
      protected against inhibition of CCE. I(Cl(Ca)) was similar in Bcl-2
      overexpressing and control oocytes when intracellular Ca(2+) store depletion was
      induced by microinjection of inositol 1,4,5-trisphosphate (InsP(3)) and other
      means and when CCE was induced by means independent of SERCA inhibition. Our data
      indicate that Bcl-2 affects neither the InsP(3) receptor nor Ca(2+) entry itself.
      At the end of a 24-h period after progesterone addition to the medium, only 25%
      of Bcl-2-overexpressing oocytes had matured compared to 85% of control oocytes.
      Our data suggest that SERCA participates in Xenopus oocyte maturation by
      controlling cytosolic Ca(2+) and/or intracellular Ca(2+) stores, hence CCE. An
      observed progesterone-dependent protein kinase-catalysed phosphorylation of SERCA
      is further indication of its role in oocyte maturation.

PMID- 11314029
TI  - Cellular and viral Fos proteins are degraded by different proteolytic systems.
AB  - c-Fos proto-oncoprotein is a short-lived transcription factor degraded by the
      proteasome in vivo. Its mutated forms expressed by the mouse osteosarcomatogenic
      retroviruses, FBJ-MSV and FBR-MSV, are stabilized two- and threefold,
      respectively. To elucidate the mechanisms underlying v-Fos(FBJ) and v-Fos(FBR)
      protein stabilization, we conducted a genetic analysis in which the half-lives
      and the sensitivities to various cell-permeable protease inhibitors of a variety
      of cellular and viral protein mutants were measured. Our data showed that the
      decreased degradation of v-Fos(FBJ) and v-Fos(FBR) is not simply explained by the
      deletion of a c-Fos destabilizing C-terminal domain. Rather, it involves a
      complex balance between opposing destabilizing and stabilizing mutations which
      are distinct and which include virally-introduced peptide motifs in both cases.
      The mutations in viral Fos proteins conferred both total insensitivity to
      proteasomal degradation and sensitivity to another proteolytic system not
      naturally operating on c-Fos, explaining the limited stabilization of the two
      proteins. This observation is consistent with the idea that FBR-MSV and FBJ-MSV
      expression machineries have evolved to ensure controlled protein levels.
      Importantly, our data illustrate that the degradation of unstable proteins does
      not necessarily involve the proteasome and provide support to the notion that
      highly related proteins can be broken down by different proteolytic systems in
      living cells.

PMID- 11314030
TI  - Activation of the focal adhesion kinase signaling pathway by structural
      alterations in the carboxyl-terminal region of c-Crk II.
AB  - The Crk II adaptor protein encodes an SH2/SH3-domain containing adaptor protein
      with an SH2-SH3-SH3 domain structure that transmits signals from tyrosine
      kinases. The two SH3 domains are separated by a 54 amino acid linker region,
      whose length is highly conserved in xenopus, chicken, and mamalian Crk II
      proteins. To gain a better understanding into the role of the C-terminal region
      of Crk, we generated a series of C-terminal SH3 domain and SH3 linker mutants and
      examined their role in tyrosine kinase pathways. Expression of point mutations in
      the C-terminal SH3 domain (W276K Crk), at the tyrosine phosphorylation site
      (Y222F Crk II), or truncation of the entire C-terminus (Crk I or Crk Delta242),
      all increased c-Abl binding to the N-terminal SH3 domain of Crk and, where
      relevant, increased Tyr(222) phosphorylation. Deletion analysis of c-Crk II also
      revealed the presence of a C-terminal segment important for trans-activation of
      FAK. Such mutants, Crk Delta255 or Crk Delta242 Extended Linker (Crk
      Delta242([EL])), characterized by a disruption in the SH3 linker/C-terminal SH3
      boundary, induced robust hyperphosphorylation of focal adhesion kinase (FAK) on
      Tyr(397), hyperphosphorylation of focal adhesion proteins p130(cas) and paxillin
      and increased focal adhesion formation in NIH3T3 cells. The effects of Crk
      Delta242([EL]) could be abrogated by co-expression of dominant negative c-Src or
      the protein tyrosine phosphatase PTP-PEST, but not by dominant negative Abl. Our
      results suggest that the C-terminal region of Crk contains negative regulatory
      elements important for both Abl and FAK dependent signal pathways, and offers a
      paradigm for an autoinhibitory region in the SH3 linker/C-terminal SH3 domain.

PMID- 11314031
TI  - RB regulates transcription of the p21/WAF1/CIP1 gene.
AB  - We have previously shown that RB plays an important role in the maintenance of
      the epithelial phenotype. p21 is also involved in several terminal
      differentiation systems including keratinocytes. We report here that p21 is an RB
      target gene in epithelial cells, but not in fibroblasts where RB is unable to
      transactivate p21 transcriptional expression. In epithelial cells, when RB family
      factors were inactivated by SV40 T antigen (LT), p21 expression was strongly
      repressed, whereas its expression was not affected when the cells were
      transformed by a mutated LT leaving RB active but inactivating p53. Moreover,
      retransformation by RB of LT transformed epithelial cells totally restored p21
      expression. By cotransfection experiments and using deletions and point mutations
      of the p21 promoter, we show that the minimal region required for the RB-mediated
      transcriptional activation maps to a GC-rich region located between -83 and -74.
      This region is shown to interact specifically with the transcription factor Sp1
      and Sp3. Thus for the first time, we show a positive transcriptional relationship
      between RB and p21 in epithelial cells. Since p21 keeps RB in a
      hypophosphorylated state important for its transcriptional activity during
      differentiation, our results imply an auto-loop of regulation between RB and p21
      that may be essential for the maintenance of the differentiation state. We
      propose that this transcriptional relationship might be necessary of their roles
      in cell cycle arrest and in several differentiation pathways.

PMID- 11314032
TI  - The designer cytokine hyper-IL-6 mediates growth inhibition and GM-CSF-dependent
      rejection of B16 melanoma cells.
AB  - The low immunogenic B16 melanoma cell line was transfected with a mammalian
      expression vector containing the complementary DNA for a sIL-6R/IL-6 fusion
      protein, termed Hyper-IL-6 (H-IL-6), which was shown to have biological
      activities at 100-1000-fold lower concentrations than IL-6 in combination with
      sIL-6R. The secreted p84 glycoprotein was detected in the supernatant of
      transfected cells and was fully active on BAF3/gp130 cells, which respond to IL
      6/sIL-6R but not to IL-6 alone. Administration of recombinant H-IL-6 to C57BL/6
      mice resulted in a prolonged acute phase protein gene expression indicating long
      systemic persistence of the fusion protein. Transfected B16 cells (B16/H-IL6
      cells) showed morphological alterations in combination with a dramatic growth
      inhibition in vitro. Subcutaneous injection in C57BL/6 mice resulted in an almost
      complete rejection of B16/H-IL6 cells. This effect was partially abolished in
      FVB/BL/6 mice transgenic for a GM-CSF receptor antagonist, indicating a GM-CSF
      dependent rejection of H-IL-6 transfected B16 cells. These results demonstrate
      that the anti-tumor effect of cytokines like IL-6 which are secreted by
      transfected melanoma cells at least in part depends on GM-CSF activity.

PMID- 11314033
TI  - Cloning and characterization of a senescence inducing and class II tumor
      suppressor gene in ovarian carcinoma at chromosome region 6q27.
AB  - Cytogenetic, molecular and functional analysis has shown that chromosome region
      6q27 harbors a senescence inducing gene and a tumor suppressor gene involved in
      several solid and hematologic malignancies. We have cloned at 6q27 and
      characterized the RNASE6PL gene which belongs to a family of cytoplasmic RNases
      highly conserved from plants, to man. Analysis of 55 primary ovarian tumors and
      several ovarian tumor cell lines indicated that the RNASE6PL gene is not mutated
      in tumor tissues, but its expression is significantly reduced in 30% of primary
      ovarian tumors and in 75% of ovarian tumor cell lines. The promoter region of the
      gene was unaffected in tumors cell lines. Transfection of RNASE6PL cDNA into HEY4
      and SG10G ovarian tumor cell lines suppressed tumorigenicity in nude mice. When
      tumors were induced by RNASE6PL-transfected cells, they completely lacked
      expression of RNASE6PL cDNA. Tumorigenicity was suppressed also in RNASE6PL
      transfected pRPcT1/H6cl2T cells, derived from a human/mouse monochromosomic
      hybrid carrying a human chromosome 6 deleted at 6q27. Moreover, 63.6% of HEY4
      clones and 42.8% of the clones of XP12ROSV, a Xeroderma pigmentosum SV40
      immortalized cell line, transfected with RNASE6PL cDNA, developed a marked
      senescence process during in vitro growth. We therefore propose that RNASE6PL may
      be a candidate for the 6q27 senescence inducing and class II tumor suppressor
      gene in ovarian cancer.

PMID- 11314034
TI  - PKC delta mediates ionizing radiation-induced activation of c-Jun NH(2)-terminal
      kinase through MKK7 in human thyroid cells.
AB  - The thyroid gland is one of the most sensitive organs in ionizing radiation (IR)
      induced carcinogenesis. To determine, therefore, the specific cascade of IR
      induced signal transduction in human thyroid cells, we investigated the
      functional role of protein kinase C (PKC), especially its interlocking activation
      of c-Jun NH(2)-terminal kinase (JNK) pathway. In the present study, using
      adenovirus expression vectors for diverse dominant-negative (DN) types of PKC
      isoforms (alpha, beta2, delta, epsilon and zeta) expressed in primary cultured
      human thyroid cells, only DN/PKC delta suppressed IR-induced JNK activation. In
      addition, Rottlerin, a PKC delta specific inhibitor, inhibited IR-induced JNK
      activation. IR-induced activation of transcription factor AP-1, downstream target
      of JNK, was also attenuated by DN/PKC delta. To examine the involvement of
      upstream kinases of JNK, we performed immune-complex kinase assays of mitogen
      activated protein kinase kinase 4 (MKK4) and MKK7. IR activated MKK7 but not
      MKK4, and this activation was inhibited by Rottlerin. Furthermore, IR-induced JNK
      activation was suppressed by overexpression of kinase-deficient MKK7. Our results
      indicate that IR selectively activates the cascade of PKC delta-MKK7-JNK-AP-1 in
      human thyroid cells, suggesting a not apoptotic but radio-resistant role of PKC
      delta in human thyroid cells following IR.

PMID- 11314035
TI  - A nude mice model of human rhabdomyosarcoma lung metastases for evaluating the
      role of polysialic acids in the metastatic process.
AB  - PSA is an oncodevelopmental antigen usually expressed in human tumors with high
      metastatic potential. Here we set up a metastatic model in nude mice by using
      TE671 cells, which strongly express PSA-NCAM. We observed the formation of lung
      metastases when TE671 cells were injected intravenously, intramuscularly, and
      intraperitoneally, but not subcutaneously. Intraperitoneal injections also
      induced peritoneal carcinosis, ascites, and liver metastases. To evaluate the
      putative role of PSA in the metastatic process we used a specific cleavage of PSA
      on NCAM by endoneuraminidase-N on intraperitoneal primary tumors. Mice with
      primary intramuscular tumors were taken as control. Repeated injections of
      endoneuraminidase-N led to a decrease in PSA expression in primary
      intraperitoneal nodules and ascites but not in intramuscular primary tumors.
      Endoneuraminidase-N also increased the delay in ascitic formation and decreased
      the number of lung or liver metastases in the case of intraperitoneal tumors but
      not in the case of intramuscular tumors. When metastases occurred in
      endoneuraminidase-N injected animals, they strongly expressed PSA-NCAM.
      Therefore, we established a relationship between PSA expression on the surface of
      primary tumor cells and the metastatic process.

PMID- 11314036
TI  - Searching for microsatellite mutations in coding regions in lung, breast, ovarian
      and colorectal cancers.
AB  - RepX represents a new informatics approach to probe the UniGene database for
      potentially polymorphic repeat sequences in the open reading frame (ORF) of
      genes, 56% of which were found to be actually polymorphic. We now have performed
      mutational analysis of 17 such sites in genes not found to be polymorphic (<0.03
      frequency) in a large panel of human cancer genomic DNAs derived from 31 lung, 21
      breast, seven ovarian, 21 (13 microsatellite instability (MSI)+ and eight MSI-)
      colorectal cancer cell lines. In the lung, breast and ovarian tumor DNAs we found
      no mutations (<0.03-0.04 rate of tumor associated open reading frame mutations)
      in these sequences. By contrast, 18 MSI+ colorectal cancers (13 cancer cell lines
      and five primary tumors) with mismatch repair defects exhibited six mutations in
      three of the 17 genes (SREBP-2, TAN-1, GR6) (P<0.000003 compared to all other
      cancers tested). We conclude that coding region microsatellite alterations are
      rare in lung, breast, ovarian carcinomas and MSI (-) colorectal cancers, but are
      relatively frequent in MSI (+) colorectal cancers with mismatch repair deficits.

PMID- 11314037
TI  - Cytotoxicity of Tumor necrosis factor related apoptosis-inducing ligand towards
      Ewing's sarcoma cell lines.
AB  - Death ligands of the Tumor Necrosis Factor (TNF) family are known to induce
      apoptosis upon binding to their cognate receptors. However, the clinical utility
      of these cytokines as anticancer agents has been limited due to unacceptable
      toxicity. TRAIL is a recently isolated death ligand that possesses selective anti
      tumor activity against a number of cancer cell lines without significant systemic
      toxicity. In this report we present evidence that cell lines derived from Ewing's
      Sarcoma (ES) are uniformly sensitive to TRAIL-mediated apoptosis. Furthermore,
      unlike TNF-alpha, treatment with TRAIL fails to induce the anti-apoptotic and pro
      inflammatory NF-kappaB pathway in the ES cell lines. Our results suggest that
      TRAIL may prove to be a useful agent for the treatment of Ewing's sarcoma and
      related peripheral neuroectodermal tumors.

PMID- 11314038
TI  - Human ARF binds E2F1 and inhibits its transcriptional activity.
AB  - The INK4a/ARF locus which is frequently inactivated in human tumours encodes two
      different tumour suppressive proteins, p16(INK4a) and ARF. p16(INK4a) is a major
      component of the RB pathway. ARF is part of an ARF-mdm2-p53 network that exerts a
      negative control on hyperproliferative signals emanating from oncogenic stimuli.
      Among these is the transcription factor E2F1, a final effector of the RB pathway,
      that induces ARF expression. Recent data suggest that ARF function is not
      restricted to the p53 pathway. However, ARF target(s) implicated in this p53
      independent function remains to be identified. We show that ARF is able to
      inhibit the proliferation of human cell lines independently of their p53 status.
      In this context, we demonstrate that ARF interacts physically with E2F1 and
      inhibits its transcriptional activity. Moreover, we show that mdm2 is required
      for the modulation of E2F1 activity by ARF. Beside the well-known p53 and mdm2
      partners, these results identify E2F1 as a new ARF target. Thus, ARF can be
      viewed as a dual-acting tumour suppressor protein in both the p53 and RB
      pathways, further emphasizing its role in tumour surveillance.

PMID- 11314039
TI  - Characterization of an alternatively spliced AATYK mRNA: expression pattern of
      AATYK in the brain and neuronal cells.
AB  - The AATYK gene encodes a tyrosine kinase whose expression is up-regulated during
      the apoptosis and differentiation of 32Dcl3 myeloblastic cells. Because high
      levels of AATYK mRNA have also been detected in the brain, and because these
      transcripts differ in size from that observed in the 32Dcl3 cell line, it was of
      interest to determine whether this gene encodes mRNAs that are alternatively
      spliced and whether these mRNAs are expressed in a tissue-specific manner. We
      have isolated a novel, alternatively spliced AATYK mRNA using cDNA library
      screening and RT-PCR, whose expression is readily detected in the brain but not
      myeloid cells. Western blot analysis revealed that the AATYK protein was
      expressed in virtually all regions of the adult rat brain in which neurons are
      present, including olfactory bulb, forebrain, cortex, midbrain, cerebellum and
      pons. Immunohistochemical labeling of adult brain sections showed the highest
      levels of AATYK expression in the cerebellum and olfactory bulb. Expression of
      AATYK was also up-regulated as a function of RA-induced neuronal differentiation
      of p19 embryonal carcinoma cells, supporting a role for this protein in mature
      neurons and neuronal differentiation.

PMID- 11314040
TI  - Characterization of the apoptosis-associated tyrosine kinase (AATYK) expressed in
      the CNS.
AB  - We isolated three related cDNA clones from a mouse cerebellar library; the type I
      cDNA was identical to the gene encoding the apoptosis-associated tyrosine kinase
      (AATYK), whose expression in myeloid precursor cells is increased during growth
      arrest or apoptosis. Low levels of AATYK mRNA expression were seen in adult mouse
      brains but not in embryos. In situ hybridization confirmed the widespread
      expression of AATYK mRNA in neurons throughout the adult brain. AATYK possessed
      tyrosine kinase activity and was autophosphorylated when expressed in 293 cells.
      AATYK mRNA expression was rapidly induced in cultured cerebellar granule cells
      during apoptosis induced by a low concentration of KCl (5 mM). Levels of
      endogenous AATYK protein were increased only slightly, but they were accompanied
      by an increase in molecular weight during apoptosis. Results of the tyrosine
      phosphatase treatments indicated that the increase in molecular weight was partly
      caused by tyrosine phosphorylation. The number of apoptotic granule cells
      overexpressing wild-type AATYK protein was significantly greater than the number
      of apoptotic granule cells overexpressing a mutant AATYK that lacked tyrosine
      kinase activity in low concentrations of KCl. These findings suggest that through
      its tyrosine kinase activity, AATYK is involved in the apoptosis of mature
      neurons.

PMID- 11314041
TI  - Isolation and characterization of the TERE1 gene, a gene down-regulated in
      transitional cell carcinoma of the bladder.
AB  - We have identified a novel cDNA product designated transitional epithelial
      response gene (TERE1), which was localized to chromosome 1p36. The TERE1
      transcript (1.5 and 3.5 kb) is present in most normal human tissues including
      urothelium, but was reduced or absent in the majority of muscle invasive TCC
      tumors (22 out of 29 cases). The open reading frame encodes a protein of 338
      amino acids (MW 36.8 KD). This protein is 57% homologous to a Drosophila protein
      called heix. We have shown by Western blotting and immuno-histochemistry with a
      polyclonal antibody to a specific TERE1 peptide, reduced or absent staining in
      muscle invasive tumors. Transfection of a sense TERE1 construct resulted in an 80
      90% inhibition of cellular proliferation in two TCC cell lines and a lack of
      aneuploidy in the TERE1-transduced J82 cell line. These data suggest a potential
      role for this gene product in the progression of bladder cancer.

PMID- 11314042
TI  - The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to
      sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif.
AB  - The adapter Grb2 is an important mediator of normal cell proliferation and
      oncogenic signal transduction events. It consists of a central SH2 domain flanked
      by two SH3 domains. While the binding specificities of the Grb2 SH2 and N
      terminal SH3 domain [Grb2 SH3(N)] have been studied in detail, binding properties
      of the Grb2 SH3(C) domain remained poorly defined. Gab1, a receptor tyrosine
      kinase substrate which associates with Grb2 and the c-Met receptor, was
      previously shown to bind Grb2 via a region which lacks a Grb2 SH3(N)-typical
      motif (P-x-x-P-x-R). Precipitation experiments with the domains of Grb2 show now
      that Gab1 can bind stably to the Grb2 SH3(C) domain. For further analyses, Gab1
      mutants were generated by PCR to test in vivo residues thought to be crucial for
      Grb2 SH3(C) binding. The Grb2 SH3(C) binding region of Gab1 has significant
      homology to a region of the adapter protein SLP-76. Peptides corresponding to
      epitopes SLP-76, Gab1, SoS and other proteins with related sequences, as well as
      mutant peptides were synthesized and analysed by tryptophan-fluorescence
      spectrometry and by in vitro competition experiments. These experiments define a
      13 amino acid sequence with the unusual consensus motif P-x-x-x-R-x-x-K-P as
      required for a stable binding to the SH3(C) domain of Grb2. Additional analyses
      point to a distinct binding specificity of the Grb2-homologous adapter protein
      Mona (Gads), indicating that the proteins of the Grb2 adapter family may have
      partially overlapping, yet distinct protein binding properties.

PMID- 11314043
TI  - Cell type specific involvement of death receptor and mitochondrial pathways in
      drug-induced apoptosis.
AB  - Apoptosis in response to cellular stress such as treatment with cytotoxic drugs
      is mediated by effector caspases (caspase-3) which can be activated by different
      initiator pathways. Here, we report on a cell type specific triggering of death
      receptor and/or mitochondrial pathways upon drug treatment. In type I cells
      (BJAB), both the receptor and the mitochondrial pathway were activated upon drug
      treatment, since blockade of either the receptor pathway by overexpression of
      dominant negative FADD (FADD-DN) or of the mitochondrial pathway by
      overexpression of Bcl-X(L) only partially inhibited apoptosis. Drug treatment
      induced formation of a FADD- and caspase-8-containing CD95 death-inducing
      signaling complex (DISC) in type I cells resulting in activation of caspase-8 as
      the most apical caspase. In contrast, in type II cells (Jurkat), apoptosis was
      predominantly controlled by mitochondria, since overexpression of Bcl-2
      completely blocked drug-induced apoptosis, while overexpression of FADD-DN had no
      protective effect. In these cells, caspases including caspase-8 were activated by
      mitochondria-driven signaling events and no DISC was detected despite expression
      levels of CD95, FADD and caspase-8 proteins comparable to type I cells. Likewise,
      drug-induced CD95 aggregation was predominantly found in type I cells. Bid was
      cleaved prior to mitochondrial alterations in type I cells providing a molecular
      link between caspase-8 activation and mitochondrial perturbations, whereas in
      type II cells, Bid was cleaved downstream of mitochondria. Our findings of a cell
      type specific response to cytotoxic drugs have implications for the
      identification of molecular parameters for chemosensitivity or resistance in
      different tumor cells.

PMID- 11314045
TI  - Control of cell cycle progression in human mesothelioma cells treated with gamma
      interferon.
AB  - Recombinant human interferon gamma (r-hu-IFNgamma) exerts both antitumoral
      activity in the early stages of human malignant mesothelioma and a cytostatic
      effect in human mesothelioma (HM) cell lines in vitro. The antiproliferative
      effect of interferons (IFNs) reported in a variety of cells has been attributed
      to several mechanisms. In order to progress in the understanding of HM cell
      growth modulation by r-hu-IFNgamma, modifications of cell cycle progression and
      expression of key cell cycle regulator proteins in response to r-hu-IFNgamma were
      examined. Nine HM cell lines were studied, including one resistant to the
      antiproliferative effect of r-hu-IFNgamma. Except in the resistant cell line r-hu
      IFNgamma produced an arrest in the G1 and G2-M phases of the cell cycle,
      associated with a reduction in both cyclin A and cyclin dependent kinase
      inhibitors (CDKIs) expression. Moreover cyclin B1/cdc2 activity was decreased.
      The present study provides the first evidence of a G2-arrest in r-hu-IFNgamma
      treated HM cell lines and indicates that HM cell lines, despite their tumorigenic
      origin still support cell cycle control. The cell cycle arrest induced by r-hu
      IFNgamma seems to depend on cyclin regulation through p21(WAF1/CIP1)- and
      p27(Kip1)-independent mechanisms and is not directly related to the induced DNA
      damage.

PMID- 11314044
TI  - Phosphorylation of serines 15 and 37 is necessary for efficient accumulation of
      p53 following irradiation with UV.
AB  - Changes in the phosphorylation state of p53 are important in increasing its half
      life and potency as a transcription factor. To investigate their roles, serine
      residues 15 and 37 were mutated to alanines and the mutated proteins were
      expressed stably at low basal levels in Li-Fraumeni-derived p53-null human
      fibroblasts. The accumulation of p53 after DNA damage was analysed quantitatively
      in multiple clones. Mutation of serine 15, serine 37 or both impaired the
      accumulation of the protein after exposing the cells to ultraviolet radiation (50
      100% increase for the mutant proteins, 500% increase for wild-type p53) but not
      after treatment with adriamycin. The diminished accumulation of mutant p53
      protein is due to a reduction of basal HDM association. Analysis of p53-dependent
      transcription revealed that phosphorylation of serine 15 is required to maintain
      basal levels of p21 mRNA. These results provide new evidence for an important
      function of serine 37 phosphorylation, clearly distinguish the pathways of p53
      activation in response to ultraviolet radiation or DNA damage inflicted by
      adriamycin, and reveal that serine 15 is crucial to support the p53-mediated
      basal expression of p21.

PMID- 11314046
TI  - Direct trans-activation of the human cyclin D2 gene by the oncogene product Tax
      of human T-cell leukemia virus type I.
AB  - Cyclins are one of the pivotal determinants regulating cell cycle progression. We
      previously reported that the trans-activator Tax of human T-cell leukemia virus
      type I (HTLV-I) induces endogenous cyclin D2 expression along with cell cycle
      progression in a resting human T-cell line, Kit 225, suggesting a role of cyclin
      D2 in Tax-mediated cell cycle progression. The cyclin D2 gene has a typical E2F
      binding element, raising the possibility that induction of cyclin D2 expression
      is a consequence of cell cycle progression. In this study, we examined the role
      and molecular mechanism of induction of the endogenous human cyclin D2 gene by
      Tax. Introduction of p19(INK4d), a cyclin dependent kinase (CDK) inhibitor of the
      INK4 family specific for D-type CDK, inhibited Tax-mediated activation of E2F,
      indicating requirement of D-type CDK in Tax-mediated activation of E2F.
      Previously indicated E2F binding element and two NF-kappaB-like binding elements
      in the 1.6 kbp cyclin D2 promoter fragment had little, if any, effect on
      responsiveness to Tax. We found that trans-activation of the cyclin D2 promoter
      by Tax was mainly mediated by a newly identified NF-kappaB-like element with
      auxiliary contribution of a CRE-like element residing in sequences downstream of 
      444 which were by themselves sufficient for trans-activation by Tax. These
      results indicate that Tax directly trans-activates the cyclin D2 gene, resulting
      in growth promotion and perhaps leukemogenesis through activation of D-type CDK.

PMID- 11314047
TI  - Quantitative real-time PCR does not show selective targeting of p14(ARF) but
      concomitant inactivation of both p16(INK4A) and p14(ARF) in 105 human primary
      gliomas.
AB  - In many human cancers, the INK4A locus is frequently mutated by homozygous
      deletions. By alternative splicing this locus encodes two non-related tumor
      suppressor genes, p16(INK4A) and p14(ARF) (p19(ARF) in mice), which regulate cell
      cycle and cell survival in the retinoblastoma protein (pRb) and p53 pathways,
      respectively. In mice, the role of p16(INK4A) as the critical tumor suppressor
      gene at the INK4A locus was challenged when it was found that p19(ARF) only knock
      out mice developed tumors, including gliomas. We have analysed the genetic status
      of the INK4A locus in 105 primary gliomas using both microsatellite mapping (MSM)
      and quantitative real-time PCR (QRT-PCR). Comparison of the results of the two
      methods revealed agreement in 67% of the tumors examined. In discordant cases,
      fluorescence in situ hybridization (FISH) analysis was always found to support
      QRT-PCR classification. Direct assessment of p14(ARF) exon 1beta, p16(INK4A) exon
      1alpha and exon 2 by QRT-PCR revealed 43 (41%) homozygous and eight (7%)
      hemizygous deletions at the INK4A locus. In 49 (47%) gliomas, both alleles were
      retained. In addition, QRT-PCR, but not MSM, detected hyperploidy in five (5%)
      tumors. Deletion of p14(ARF) was always associated with co-deletion of p16(INK4A)
      and increased in frequency upon progression from low to high grade gliomas.
      Shorter survival was associated with homozygous deletions of INK4A in the
      subgroup of glioblastoma patients older than 50 years of age (P=0.025, Anova test
      single factor, alpha=0.05).

PMID- 11314048
TI  - Modulation of phospholipase D by hexadecylphosphorylcholine: a putative novel
      mechanism for its antitumoral activity.
AB  - Hexadecylphosphorylcholine (HePC, D-18506, INN: Mitelfosine) belongs to the
      family of alkylphosphocholines with anticancer activity. Previous reports have
      related its antitumoral activity to their ability to interfere with phospholipid
      metabolism. However a clear mechanism of action has not been established yet. We
      have investigated the effect of HePC on two enzymes recently reported to play a
      role in cell growth proliferation, phospholipase D (PLD) and choline kinase
      (ChoK). Our results demonstrate that treatment with HePC induces a rapid
      stimulation of PLD, that may be achieved by PKC dependent or independent
      mechanisms, depending on the cell line investigated. Both PLD1 and PLD2
      isoenzymes are sensitive to HePC activation. By contrast, no effect was observed
      by HePC on ChoK, a new target for anticancer drug development. Furthermore, in
      all cell lines tested, a chronic exposure of the cells to HePC abrogates PLD
      activation by either phorbol esters or HePC itself with no effect on total
      cellular PLD levels. This is reflected in a strong inhibition of PLD activity. We
      suggest that the inhibitory effects on PLD by HePC may be related to its
      antitumoral action.

PMID- 11314049
TI  - Transforming ability of Gag-Myc fusion proteins correlates with Gag-Myc protein
      stability and transcriptional repression.
AB  - Avian retroviruses that have transduced c-myc are useful tools to study the
      conditions necessary for cellular transformation. FH3, one such retrovirus which
      encodes a Gag-Myc fusion protein, is not transforming in quail embryonic
      fibroblasts, but a late variant of FH3 that arose after passaging FH3-infected
      cells is transforming. Mutational analysis of FH3 revealed that the presence of a
      portion of the retroviral protease in FH3 inhibited transformation and that this
      inhibition was transferable to a more highly transforming retrovirus, MC29.
      Transforming and non-transforming FH3-derived and MC29-derived Gag-Myc proteins
      were used to further explore characteristics of Myc necessary for transformation.
      Gag-Myc proteins which were transforming were found to be the most stable in the
      cell. To distinguish whether transactivation and/or repression is correlated to
      transformation, the various Gag-Myc fusion proteins were tested for their ability
      to activate or repress c-Myc targets. Results indicated that a correlation exists
      between transforming Gag-Myc proteins and their ability to repress, whereas all
      Gag-Myc proteins could transactivate, regardless of their ability to transform.
      Taken together, these results suggest that protein stabilization of Myc and
      repression of target genes by Myc are important for cellular transformation.

PMID- 11314050
TI  - Towards a blueprint of the cell cycle.
AB  - The understanding of the organisation of cell cycle events is of utmost
      importance to devise effective therapeutic strategies for cancer. In this article
      we gather evidences from the literature in support of a system model of the cell
      cycle, in which a growth-sensitive threshold controls entry into S phase and the
      sequential activation of cyclin-dependent kinases. The cycle is terminated by an
      End function, that comprises events from the onset of mitosis to cell division
      and that may also be modulated by the increase of cell size. This blueprint
      allows quantitative predictions by computer simulations of steady and transitory
      states. In fact, we show that the proposed control system applies to budding
      yeast populations during nutritional shift-up and following hyperactivation of
      the cAMP signalling pathway. Besides the growth-sensitive control system it is
      shown to apply to mammalian cells both in the exit from quiescence and in active
      proliferation. The putative molecular determinants that set the threshold
      controlling S phase entry are consistently altered in cancer cells. Finally, we
      discuss an input/output analysis based on the simulated behaviour derived from
      the blueprint as a new tool to investigate the road to cancer.

PMID- 11314051
TI  - Transcription factor ATF3 partially transforms chick embryo fibroblasts by
      promoting growth factor-independent proliferation.
AB  - Activating Transcription Factor 3 (ATF3) is a member of the bZip family of
      transcription factors. Previous studies in mammalian cells suggested that like
      other bZip family members e.g. Jun and Fos, ATF3 might play a role in the control
      of cell proliferation and participate in oncogenic transformation. To investigate
      this putative ATF3 function directly, the rat ATF3 protein was compared with v
      Jun for its ability to transform primary cultures of chick embryo fibroblasts
      (CEFs). Like CEFs accumulating v-Jun, CEFs accumulating the ATF3 protein
      displayed a typical, fusiform morphology, associated with an enhanced capacity to
      grow in medium with reduced amount of serum. However, in contrast to v-Jun
      transformed CEFs, the ATF3 overexpressing cells could not promote colony
      formation from single cells in agar. Partial transformation induced by ATF3 was
      found to be associated with repression of multiple cellular genes that are also
      down-regulated by v-Jun, including those coding for the extracellular components
      fibronectin, decorin, thrombospondin 2, and the pro-apoptotic protein Par-4.
      These data demonstrate that, at least in primary avian cells, rat ATF3 possesses
      an intrinsic oncogenic potential. Moreover, the results suggest that ATF3 might
      induce growth factor independence by down-regulating a subset of the genes
      repressed by v-Jun.

PMID- 11314052
TI  - The cultural adaptability of health sciences faculty.
AB  - PURPOSE: Health care educators have a major responsibility to prepare future
      health care practitioners to provide services for culturally diverse clients. As
      a starting point, prior to making any curricular changes, the cultural
      adaptability of the faculty needs to be measured; therefore, this study was
      conducted to determine the cultural adaptability of the faculty within a College
      of Health Sciences of an urban regional university in Southeastern Virginia.
      METHODS: The sample consisted of 40 health sciences faculty representing dental
      hygiene, medical laboratory sciences, nursing and physical therapy. The principal
      investigator personally administered the Cross-Cultural Adaptability Inventory
      (CCAI), a 50-item instrument that contains questions to measure the construct
      cultural adaptability and its four dimensions: emotional resilience,
      flexibility/openness, perceptual acuity, and personal autonomy. The CCAI is not
      targeted to one particular culture, but rather is designed to be culture general.
      RESULTS: Overall, all four faculty groups exhibited higher average CCAI scores
      than the CCAI norm group which consisted of individuals with cross-cultural
      experience and training. Analysis of variance revealed no statistically
      significant difference, at the 0.05 level, in the overall CCAI scores among the
      health sciences faculty. Analysis of CCAI scores among the health sciences
      faculty, using analysis of variance revealed no statistically significant
      difference, at the 0.05 level, in emotional resilience, perceptual acuity, and
      personal autonomy. In the dimension flexibility/openness, a significant
      difference was exhibited between the physical therapy and medical laboratory
      sciences faculty. CONCLUSIONS: These qualities should provide a strong foundation
      for the development of additional competence in cross-cultural health care and
      for preparing practitioners who can provide culturally sensitive health care.
      Further exploration to determine whether a cross culturally adaptable faculty can
      impart this attribute to students might be to administer the CCAI to entering and
      exiting students.

PMID- 11314053
TI  - Negative perceptions of dental stimuli and their effects on dental fear.
AB  - PURPOSE: About 40% of modern western society are apprehensive about dental
      visits, 20% are highly fearful, and 5% avoid oral health care completely. This
      study examined how negative perceptions of dental stimuli contribute to dental
      fear. METHODS: One-hundred-and-seven people recruited from a dental school clinic
      and a private practice, participated in the study. Each participant completed
      measures of general dental anxiety (DAS-R) and negative perception of specific
      dental stimuli (DFAS). Upon completion of the scales, data were coded and
      analyzed using Statistical Package for Social Sciences. RESULTS: Data analyses
      revealed a significant correlation between negative perceptions of common dental
      stimuli and dental fear (p < .05). Getting an injection, having dental
      radiographs taken, use of scalers and curets, and the sight of the needle were
      identified as the dental stimuli evoking the highest negative perceptions by the
      sample. CONCLUSION: Because exposure to certain stimuli triggers dental fear, it
      is important to identify anxious oral health care patients, and oral health care
      providers must be sensitive to their fear. Providing a positive experience will
      help to lower negative perceptions of oral health care. If particular stimuli
      produce anxiety and fear, then ways to limit exposure to them is necessary.

PMID- 11314054
TI  - Dental hygiene public health supervision: changes in Maine law.
AB  - The author analyzed data from a set of reports submitted to the Maine Board of
      Dental Examiners by dental hygienists practicing under a new supervision category
      entitled "Public Health Supervision" enacted in Maine in 1995. The data set
      included information on public health dental hygiene applicants and projects
      reported between May 1995 and November 1998. With mounting interest from dental
      hygienists seeking to serve the population with limited access to preventive
      dental care, the regulatory board created a public health dental hygiene
      supervision category in the Maine regulations. The analysis revealed that dental
      hygienists are seeking and receiving the public health supervision endorsement.
      Sixty percent of the public health projects were implemented by dental hygienists
      in public service agencies. Those who addressed a need in their own communities
      without the benefit of a public health organization accounted for 40% of the
      applications. Examples of projects are described. The report serves as a summary
      of three years of data from which to assess future trends.

PMID- 11314055
TI  - Relationships among dental hygiene course grades, a mock board dental hygiene
      examination, and the National Board Dental Hygiene Examination.
AB  - PURPOSE: The purpose of this correlational study was to determine if a
      relationship existed among the National Board Dental Hygiene Examination (NBDHE)
      score, the mock board dental hygiene examination score (MDHE), early courses
      average (ECA), and interim (ICA) courses average, for Armstrong Atlantic State
      University dental hygiene students. METHODS: The sample comprised 130 Armstrong
      Atlantic State University dental hygiene students between and among the years
      1989 and 1995. Eleven dental hygiene courses and a mock examination score were
      correlated using SAS software. Regression analysis of this data was performed
      with MINITAB software. RESULTS: Attempts to predict the dependent variable NBDHE
      with the ECA, MDHE, ICA, and some combination of these independent variables,
      were unsuccessful due to an undesirably low R2 value (0.53) and multicollinearity
      when multiple regression was used. However, logistic regression showed that ECA,
      and MDHE to a lesser extent, notably affected probability of passing the NBDHE.
      CONCLUSIONS: Recommendations and conclusions drawn from this study include (a)
      remediation, (b) tracking student progress in the nine courses determining the
      ECA to identify weaknesses that make intervention advisable, and (c) providing
      mentoring for at-risk students.

PMID- 11314056
TI  - Better oral health for infants and toddlers: a community based program.
AB  - Effective partnerships between health professional educational institutions and
      social service community programs can result in improved health outcomes for the
      people of the community being served. Such partnerships also may contribute
      considerably to student maturation into compassionate providers who have an
      appreciation for how an individual's health and quality of life may be affected
      by societal factors. A dental hygiene program at a private university and an
      Early Head Start Program joined in partnership to develop, and implement
      successfully, a project that was highly productive and of reciprocal benefit.
      With a focus on infant oral care in general, and early childhood caries in
      particular, dental hygiene students were able to provide much needed oral health
      services to 45 families with children enrolled in the Early Head Start Program,
      at multiple rural locations in Maine. In addition to meeting the needs of the
      Early Head Start Program, the project created a foundation for student exchange
      on the issues of dental caries in very young children, and the complexity of the
      factors contributing to them. Professional dental hygienists may choose to adopt
      all or portions of this innovative project when planning for the delivery of
      dental hygiene care to specialized populations in community-based settings.

PMID- 11314057
TI  - Medical emergencies in the oral health care setting.
AB  - On any given day a patient seen by the dental hygienist has the potential of
      experiencing a life-threatening medical emergency. All dental hygiene
      practitioners should be aware of potential risks that a patient may present, take
      steps to prevent life-threatening events from occurring, and plan for problems in
      advance of their happening. The primary goal of this course is to help dental
      hygienists carry out the ethical, moral, legal, and professional obligation owed
      any patient. The course will review the basics of medical emergencies, with
      particular emphasis on those that are most likely to occur in the dental office.
      Discussion will center on general aspects of prevention and preparation, and will
      focus on the recognition and emergency treatment of specific conditions.
      Vasodepressor syncope, orthostatic hypotension, acute adrenal insufficiency,
      hyperventilation, asthma, heart failure and acute pulmonary edema,
      cerebrovascular accident seizures, hyperglycemia, hypoglycemia, myocardial
      infarction, angina pectoris, and anaphylaxis will be emphasized.

PMID- 11314058
TI  - Patients or clients?

PMID- 11314059
TI  - Vision repaired.

PMID- 11314060
TI  - Lighting up.

PMID- 11314062
TI  - Craniofacial surgery panel: another approach to a difficult problem.

PMID- 11314061
TI  - Dental hygienist and patient comparisons of fluoride varnishes to fluoride gels.
AB  - PURPOSE: The purpose of this study was to evaluate a fluoride varnish and compare
      it to fluoride gels in categories including taste, comfort, efficiency,
      discoloration, moisture control, safety, and ease of application. METHODS:
      Methods. Twenty-five licensed dental hygienists and 148 patients completed
      questionnaires comparing fluoride varnish to fluoride gel for the following
      categories: taste, comfort, efficiency, discoloration, moisture control, and
      safety. Responses were analyzed using descriptive statistics and a chi-square
      test. RESULTS: The 25 dental hygienists rated fluoride varnish (Duraphat)
      superior to fluoride gels in all categories. Eighty-three (56.5%) of the 148
      patients reported the varnish application to be more comfortable than gel while
      29 (20%) found it the same. In taste comparison, 90 (71.4%) preferred the
      varnish, while 16 (12.7%) rated it the same. The time required was reported as
      better for the varnish technique by 59 (50.4%) and equal to the gels by 32
      (20.3%). Discoloration of the teeth by the varnish was found not noticeable or
      not objectionable by 66 (49.3%) and somewhat objectionable or too noticeable for
      comfort in public by 68 (50.7%). However, 85 (64.3%) reported that they would
      choose to have the varnish treatment while 33 (25%) would not. Dental hygienist
      responses on questions 1-4 relative to the number of years in practice were not
      found to be significantly different. CONCLUSION: The patients and dental
      hygienists in this study preferred fluoride varnishes to gels. However, since
      some patients objected to the temporary discoloration, varnishes may not be
      suitable for everyone.

PMID- 11314063
TI  - Endoscopic transglabellar approach to the anterior fossa and paranasal sinuses.
AB  - Historically, surgical management of tumors of the anterior cranial fossa with
      extension to the paranasal sinuses has been problematic. Wide exposure of these
      lesions has traditionally called for prolonged retraction of the frontal lobes or
      potentially disfiguring transfacial approaches, subjecting patients to
      undesirable neurological and cosmetic morbidity. With the introduction of
      progressively less invasive procedures, however, intracranial tumors with
      craniofacial involvement have become amenable to en bloc resection with a minimum
      of deleterious consequences. Increasing experience with endoscopy as an imaging
      modality in intracranial and extracranial surgery has led to the adaptation of
      endoscopic techniques to this setting. We have used an entirely endoscopic
      transglabellar approach to the anterior fossa to resect suprasellar tumors in two
      patients. The use of endoscopy allowed thorough visualization of all critical
      structures at the paramedian skull base without the need for a bicoronal scalp
      flap, bifrontal osteotomies, or brain retraction. Both lesions were resected in
      their entirety with no perioperative complications and with acceptable cosmetic
      results. These cases demonstrate how the application of endoscopy to surgery of
      the anterior skull base and craniofacial skeleton can eliminate the need for
      excessively invasive techniques without compromising surgical success.

PMID- 11314064
TI  - Malignant tumors requiring maxillectomy.
AB  - Seventy cases with malignant tumors requiring maxillary resection in the past 10
      years were reviewed, retrospectively. The primary site of tumor was adjacent skin
      in 53%, maxillary sinus or maxilla in 20%, palate and alveolar arch in 13%, lip
      and buccal mucosa in 13%, and mandible in 1% of the cases. The most common
      histopathological diagnoses was squamous cell carcinoma (54%), followed by basal
      cell carcinoma (20%). Most of the patients had advanced tumors, either neglected
      or recurred. Orbital exenteration was performed in 28 cases, mandibulectomy in
      six cases, combined craniofacial resection in seven cases, and radical neck
      dissection in 18 cases. Major skin loss was present in majority of the patients.
      Postsurgical defects were reconstructed with pedicled flaps in 37 cases and free
      flaps in 12 cases. Lining of the maxillary sinus defects was provided with split
      thickness skin grafts. Patients with palatal defects were encouraged to use
      prosthetic obturators. Postoperative radiotherapy was performed in 32 patients
      and combined radiotherapy and chemotherapy in 12 patients. Communication could be
      established with only 52 patients. Sixty-three percent of them have survived
      without recurrence and distant metastasis. Resection of the tumor with free
      surgical margins and appropriate evaluation of the surgical defect for the most
      suitable reconstruction are the mainstays of treatment of the midfacial tumors.

PMID- 11314065
TI  - Determining the optimal time for consolidation after distraction osteogenesis.
AB  - The consolidation period, one of the biological factors participating in the
      distraction osteogenesis phenomenon, has not been elucidated. Parameters to
      assess new bone formation and consolidation in craniofacial distraction have been
      borrowed from the orthopedic experience. Up until now, the decision to
      discontinue distraction has been based more on personal experience than on
      objective data. By using Scintigraphy with Tc99 DP a method has been developed to
      accurately assess the termination of the consolidation phase. Scintigraphic
      evidence of consolidation was seen between the fourth and the fifth week after
      terminating distraction in infants (younger than 12 months). Not before the 10th
      week in children and between the 10th and the 14th week in adolescents and
      adults. The data roughly correlates with previous reports. It is believed that
      the consolidation period should be addressed in biologic terms and not in
      radiologic terms as done up until now. A method is proposed that offers objective
      qualitative and quantitative data for the noninvasive evaluation of bone
      consolidation which could have further applications in distraction of the
      craniofacial skeleton.

PMID- 11314066
TI  - Functional matrix cleft repair: a common strategy for unilateral and bilateral
      clefts.
AB  - At first glance, the morphologies of unilateral and bilateral clefts appear quite
      distinct. So much so, that many authors describe them as separate entities
      altogether. This has given rise to disparate surgical strategies. This paper
      presents a unifying theory of pathogenesis and treatment.

PMID- 11314067
TI  - Bioceramics as an option in correction of facial skeleton deformities.
AB  - The removal of certain deformities of facial bones is a prerequisite to a
      restoration of function, stability, and appearance. Synthetic bone substitutes
      are beneficial in cases where other operative technique would represent an
      inadequate burden for a patient. A result is achieved in one surgical
      intervention with low costs and low demands on technical equipment. Biocompatible
      nonresorbable glass-ceramics based on oxyfluoroapatite and wollastonite
      presenting osteoconductivity permits osteointegration, i.e., direct
      physicochemical bonds between live bone tissue and the implant without formation
      of a fibrous capsule. It presents better durability to stress in simulated body
      fluid than the usually used hydroxyapatite. It was used for restoration of facial
      skeletal framework contour in 14 cases under conditions where prior solutions
      were doubtful. Good results were reached in all patients. The mean time of
      observation was 18 months. During that period, the rate of complications was
      14.3%. This approach may be found to be a suitable technique, especially for
      patients exhausted by prior unsuccessful treatment but still not acquiesced in a
      result.

PMID- 11314068
TI  - Saethre-Chotzen syndrome: review of the literature and report of a case.
AB  - Saethre-Chotzen syndrome is an autosomal acrocephalosyndactyly syndrome whose
      gene has been assigned to chromosome 7p (TWIST). A case of a 13-year-old girl
      with Saethre-Chotzen syndrome (ACS III) is described. The features of the
      syndrome include: turriplagiocephaly with a cranial circumference of 52 cm,
      facial asymmetry, low hairline, proptosis, antimongoloid slanting of palpebral
      fissures, nasal deviation with high bridge, angled ears, scoliosis and
      torticollis, clinodactyly of the fourth and fifth toes, large halluxes, and
      neurosensorial hypoacusia. For correction of the deformity, a cranioorbital
      remodeling was performed. The craniofacial approach with remodeling of the
      frontal bar and reduction of the turricephaly resulted in a satisfactory
      morphological and functional outcome, with complete three-dimensional reshaping
      and remodeling of the frontonasoorbital area.

PMID- 11314069
TI  - Pneumosinus dilatans multiplex, mental retardation, and facial deformity.
AB  - Pneumosinus dilatans is a term used to describe enlargement of one or more
      paranasal sinuses without radiological evidence of localized bone destruction,
      hyperostosis, or mucous-membrane thickening. To date, many cases have been
      reported that involved frontal, ethmoid, sphenoid, and maxillary sinus. However,
      no case has been reported that involved all paranasal sinuses. Our case involved
      mastoid air cells as well as all paranasal sinuses. It is named pneumosinus
      dilatans multiplex by us. This is the first case to be reported in English
      literature that has this syndromic condition of pneumosinus dilatans multiplex,
      mental retardation, and facial deformity.

PMID- 11314070
TI  - Periodontal evaluation in patients undergoing maxillary expansion.
AB  - Maxillary transverse diameter expansion is a treatment various authors have
      claimed is related to the development of gingival recession on the teeth of the
      upper arch. The aim of the present study was to compare such an incidence in two
      different groups of patients: those treated with surgically assisted rapid
      maxillary expansion and orthopedic expansion, respectively. Both treatments
      achieved the goal of expanding the transverse dimension (5.3 and 4.4 mm,
      respectively), but a significant difference was shown by the chi 2 test for the
      incidence of gingival recession of premolar/molar upper teeth, more than double
      for the latter than for the former. Therefore, surgically assisted rapid
      maxillary expansion seems to be an orthodontically effective procedure, safer
      than the orthopedic treatment regarding the possible development of mucogingival
      problems.

PMID- 11314071
TI  - BoneSource solidification: a comparison between water and sodium phosphate as the
      solvent.
AB  - The purpose of this study was to determine the solidification rates for
      BoneSource (hydroxyapatite cement) mixed with sterile water versus BoneSource
      mixed with 0.25 ml of sodium phosphate. The average time for cure for BoneSource
      mixed with sterile water was 99 minutes, with a SD of 5.3 minutes. The average
      time for cure for BoneSource and sodium phosphate was 43 minutes, with a SD of
      3.6 minutes (P < 0.0003). The average temperature for BoneSource in sterile water
      was 19.1 degrees C with a SD of 0.082, and the average temperature of BoneSource
      in sodium phosphate was 20.1 degrees C, with a SD of 0.1. Therefore, sodium
      phosphate shows that there is a significantly decreased amount of time required
      to solidify BoneSource and it remains isothermic throughout this reaction.

PMID- 11314072
TI  - Current considerations for myelomeningocele repair.
AB  - Important advances have been made in the reconstruction of myelomeningocele
      during the last few years. Techniques of closure that use diverse tissues
      available in the back range from very simple to very complex. Most of them have
      become essential to the plastic surgeon. To facilitate a more efficient
      interdisciplinary approach, recent advances in knowledge of the vascular anatomy
      of the skin and specific clinical surgical considerations concerning skin grafts,
      cutaneous flaps, and musculocutaneous flaps are reviewed. A topographical
      division of the lesion that will permit a methodologically adequate treatment
      plan for congenital defects in the back, specifically in the thoracic,
      thoracolumbar, and lumbosacral regions is suggested.

PMID- 11314073
TI  - Re: In vitro analysis of distraction osteogenesis.

PMID- 11314074
TI  - Behavioral dentistry: a renewed paradigm for the future.
AB  - The clinical field of behavioral medicine has become firmly entrenched as an
      indispensable part of modern health care. From a biopsychosocial perspective,
      susceptibility to disease invokes a powerful mix of complex factors beyond
      biology. Behavioral pathogens can be identified which cause us to get sick, stay
      sick, and resist sound treatment. Biopsychosocially based scientific inquiry can
      contribute to a more enriched understanding of fear of dental procedures,
      management of pain, prevention of oral malignancy, and changing patterns in
      availability of dental care. Dentistry will need to take new directions in
      research to understand behavioral and psychosocial factors as well as biologic
      factors that promote and contribute to health and disease.

PMID- 11314075
TI  - Catastrophic thinking and the experience of pain during dental procedures.
AB  - In recent years, considerable research has addressed psychological predictors of
      pain, emotional distress, and avoidance in relation to dental treatment. Our work
      has focused on how "pain catastrophizing" impacts on the physical and emotional
      distress experienced during dental procedures. Pain catastrophizing refers to
      individuals' tendency to focus excessively on pain sensations and exaggerate
      their threat value, and to feel helpless in their efforts to reduce or manage
      their pain. Several studies reveal that pain catastrophizers report extreme pain
      even in response to dental procedures not typically considered to be painful. In
      this paper, we also discuss how practitioners who foster the disclosure of dental
      worries and concerns can significantly reduce the physical and emotional distress
      of patients who engage in catastrophic thinking.

PMID- 11314076
TI  - Emotional factors in temporomandibular joint disorders.
AB  - The chronic pain of many temporomandibular disorders is associated with multiple
      changes in emotional function and activities of daily living. Temporomandibular
      disorders (TMD) are similar to other chronic pain disorders in their impact on
      patients. Depression is probably the most common emotional state associated with
      chronic pain, although anxiety disorders also can be associated with TMD. The
      probability of emotional problems appears to be greatest in those individuals
      diagnosed with myofascial pain and least in those with disk displacement. Dental
      practitioners are encouraged to seek professional liaisons with mental health
      professionals who can assist them in managing chronic pain patients.

PMID- 11314078
TI  - Participation is the key to change.

PMID- 11314077
TI  - Tooth decay in our poorest children: what can we do?
AB  - Dental programs for the poor have failed to deliver improved oral health for
      children to the same degree as their more well-off counterparts. Community health
      workers continue to identify dental problems as the greatest unmet need in their
      communities. Yet, many do not see this as a problem. Practitioners need to act in
      concert through their dental societies to establish and efficiently manage
      community-based outreach programs. Child dental health can also be improved by
      increasing access through public and non-profit community clinics and integrating
      child dental services with medical care.

PMID- 11314079
TI  - Pushing the Indiana science agenda.

PMID- 11314080
TI  - Practice perfect. Atraumatic bridge removal.

PMID- 11314081
TI  - Behavioral science and the future of dentistry.

PMID- 11314082
TI  - A study of injectable tissue-engineered autologous cartilage.
AB  - OBJECTIVE: To test the effectiveness of the new techniques of tissue-engineered
      cartilage. METHODS: Chondrocytes were harvested through type II collagenase
      digestion from the auricle of New Zealand rabbits. The cells were mixed with
      alginate to generate chondrocytes/alginate composites with final cellular density
      of 50 x 10(6) per mL. Calcium chloride was used as the cross-linking agent to gel
      the aqueous alginate solution. The chondrocytes/alginate composites were injected
      into the dorsal subcutaneous tissue of New Zealand rabbits through autologous
      cells grafts. The specimens were observed during cartilage formation at 4, 8, and
      12 weeks after injection. RESULTS: Prior to harvesting, chondrocytes/alginate
      composites were easily visualized under the dorsal skin of animals. The
      appearance of experimental specimens was similar to that of native cartilage in
      gross morphology. Using a standard hematoxylin and eosin stain, the histologic
      features of all experimental specimens demonstrated new cartilage formation. With
      a Masson's trichrome and safranin O stain, the presence of collagen and
      glycosaminoglycan (GAG) was observed at 8 and 12 weeks. CONCLUSION: This study
      demonstrated that polymerization of alginate hydrogel can be controlled to allow
      injection of chondrocytes that produce new autologous cartilage at subcutaneous
      dorsal site of rabbits. Injectable tissue-engineered autologous cartilage is
      promising for potential use in oral and maxillofacial surgery.

PMID- 11314083
TI  - Distraction osteogenesis in functional reconstruction of mandible--report of 6
      cases.
AB  - OBJECTIVE: To study the application of distraction osteogenesis in mandibular
      function reconstruction. METHODS: Three types of mandibular distractors were used
      in 6 patients with different mandibular defects due to tumor resection. For 2
      cases with ramus defects, specially designed distractors were used to restore the
      normal height of the ramus. In 1 case, the trifoci distraction principle was used
      and a trifoci distractor was designed. In 3 cases, vertical distractors made in
      Germany or China were used. The patient average age was 31.5 years old (ages
      ranged from 8 to 54). RESULTS: In 5 cases the mandibular lengthenings were
      successful according to the direction and distance chosen before distraction. In
      1 case, the trifoci distraction principle was applied and a proximal 23 mm
      mandibular defect was successfully corrected; however, the 23 mm distal
      mandibular defect was not corrected because the screws for fixation of the
      transport block were loosened. Infection and dysosteogenesis did not occur in any
      cases. CONCLUSION: Distraction osteogenesis can successfully be used in
      mandibular functional reconstruction and is more advantageous than traditional
      techniques. The most favorable time for distraction osteogenesis in mandibular
      reconstruction is at the time of tumor resection.

PMID- 11314084
TI  - Computer-assisted quantitative measurements by three-dimensional images on
      zygomatic fracture deformities.
AB  - OBJECTIVE: To investigate an available method for quantitative diagnosis of
      zygomatic fractures that allow quantitative classification and diagnosis.
      METHODS: The radiographs and 2- and 3-dimensional CT images of 57 patients with
      zygomatic fractures were measured and analyzed by a computer-assisted measuring
      system before and after treatment. This was used to diagnose the displacement and
      deformity of the fractures. RESULTS: (1) Using anthropology points and a computer
      assisted measuring system, a new method was established to assess the
      displacement of the zygomatic fractures. (2) Displacement of the zygomatic
      fractures was approximately diagnosed by measuring different angles of the CT
      images. (3) A new classification was proposed based on the deformities of the
      zygomatic fractures: Type A, zygomatic body was intact and not displaced; Type B,
      zygomatic body was intact but displaced (including comminuted zygomatic arch
      fractures); Type C, zygomatic body was comminuted and displaced. (4) There were 4
      subtypes with characteristics in the most common Type B fractures. (5) Different
      images had different advantages for diagnosing zygomatic fractures. CONCLUSIONS:
      (1) Displacement of the zygomatic fractures can be quantitatively diagnosed by
      measuring 3-D CT images. (2) The computer-assisted 3-D CT measuring system is
      accurate, reliable, and clinically feasible for diagnosing zygomatic fractures.
      (3) The best image to diagnose the displacement of the fractures should be used.

PMID- 11314085
TI  - Alteration of Fas/FasL expression of oral squamous cell carcinoma cell line Tca83
      induced by retinoic acid.
AB  - OBJECTIVE: To elucidate the chemosensitivity of human tongue squamous cell
      carcinoma Tca83 cell line to all-trans retinoid acid (RA) and to determine the
      potential genetic factors mediating this sensitivity. METHODS: RA in the amounts
      of 0.1, 1, and 10 microMol/L were used to treat human cell line Tca83 in vitro.
      Cell apoptosis as well as Fas/FasL expression were analyzed by TUNEL, RT-PCR, and
      immunohistochemistry approaches. RESULTS: RA in the amounts of 1 and 10
      microMol/L RA began to inhibit cell proliferation at day 3 and had induced cell
      apoptosis on day 5. Both Fas and FasL could be detected in the treated and
      untreated cells. RA upregulated Fas mRNA and protein expression at day 5. RA had
      no obvious effect on FasL expression. CONCLUSION: The results suggest that
      apoptosis induced by RA may result from the enhancement of Fas gene transcription
      and translation.

PMID- 11314086
TI  - Expression of vascular endothelial growth factor during the early stage of
      maxillofacial blast injury.
AB  - OBJECTIVE: To determine the expression and the change of vascular endothelial
      growth factor (VEGF) and its acceptor KDR during the early stage of maxillofacial
      blast injury. To evaluate the effect of VEGF on traumatic wound healing. METHODS:
      The rabbit model of maxillofacial blast injury was made by KTY-04 blasting cap.
      The expression of VEGF and KDR in wound tissue was determined by ABC
      immunohistochemistry of 6 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after
      injury. The results were compared with preinjury groups. RESULTS: In the wound
      tissue of the maxillofacial blast injury, the expression of VEGF rose steadily
      during the first week after the injury. Compared with normal tissue, the wound
      tissue showed differences by the first day after injury, and showed significant
      differences by the third day (P < 0.01). The differences reached a peak at the
      seventh day after injury. The expression of KDR showed no difference within 3
      days after injury when compared to normal tissue. Between 5 and 7 days after
      injury, the protein was more strongly expressed. CONCLUSION: The stage of the
      VEGF expression at the maxillofacial blast injury site is similar to the
      angiopoietic stage during would healing, and KDR expression also occurs during
      that period. VEGF takes part in angiogenic cascades of traumatic wound healing
      and is produced as an auxiliary action to the regeneration of blood vessels.

PMID- 11314087
TI  - DNA-liposome complexes transduction of herpes simplex virus thymidine kinase
      renders human tongue cancer cell line sensitive to ganciclovir in vitro.
AB  - OBJECTIVE: To evaluate, in vitro, the cytotoxicity of the herpes simplex virus
      thymidine kinase (HSV1-tk) gene and ganciclovir (GCV) treatment, a widely used
      prodrug/suicide gene therapy, in human tongue cancer cell line Tbp-TL. METHODS:
      Retrovirus expressing plasmid-liposome complex transduction was used. After
      treatment with G418 for 3 weeks, the integrated HSV1-tk gene was detected by PCR
      test with the primers specifically designed for HSV1-tk cDNA; HSV1-tk mRNA was
      detected with in situ hybridization method. In vitro cytotoxicity effect of HSV
      GCV on Tbp-TL was detected with MTT and trypan blue exclusion test. RESULTS: In
      vitro experiments demonstrated dose- and time-dependent cell death by
      transduction of the HSV1-tk gene followed by GCV treatment. The IC50 (the
      concentration required to elicit 50% growth inhibition) shifted from 1000
      micrograms/mL in non-transduced Tbp-TL cells to 1.1 micrograms/mL in Tbp-TL/TK
      cells transduced with HSV1-tk gene, with the therapeutic index of 1000. Treatment
      with GCV at a dose of 10 micrograms/mL for 5 days led to complete cell death in
      HSV1-tk transduced tumor cells. When mixed with tk positive cells, the non
      transduced cells (both the parent Tbp-TL cells as well as another non-transduced
      cell, the human muco-epidermoid carcinoma cell line M3SP2) were also killed by a
      degree associated with the percentage of tk positive cells. Seventy to 90% of the
      mixed cells were killed with only 10% to 20% tk positive cells involved.
      CONCLUSION: These results suggest that the HSV-tk/GCV approach to human tongue
      cancer cell line may be efficacious, with a wide therapeutic range, and that it
      exerts a bystander effect in vitro.

PMID- 11314088
TI  - Effect of nifedipine on proliferation and DNA synthesis of human gingival
      fibroblasts.
AB  - OBJECTIVE: To investigate the effect of Nifedipine, a calcium channel blocker, on
      cellular proliferation in gingival fibroblasts in vitro. METHODS: Gingival
      fibroblasts were cultured and incubated with various concentrations of Nifedipine
      (23.5, 108, 360, and 1200 ng/mL) for up to 7 days. RESULTS: Cell numbers were
      significantly different among these groups on the sixth and seventh days,
      especially between the 1200 ng/mL or 360 ng/mL and the other concentrations.
      CONCLUSION: Nifedipine can influence proliferation of gingival fibroblasts in
      high concentrations.

PMID- 11314089
TI  - Investigation on interaction between Streptococcus sanguis and Porphyromonas
      gingivalis in specific pathogen-free rats.
AB  - OBJECTIVE: To examine whether endogenous Streptococcus can prevent or reduce the
      colonization of the virulent Porphyromonas gingivalis strain. METHODS: Successful
      implantation of the endogenous strain of S. sanguis and P. gingivalis 381 within
      14 days was demonstrated in the study rats following administration of
      doxycycline for 7 days. Thirty specific pathogen-free (SPF) rats were divided
      into 6 groups. After administration of doxycycline for 7 days, groups A and B
      were inoculated orally once a day for 5 days with P. gingivalis. Group C and E
      were inoculated orally once a day for 5 days with S. sanguis. Then, group A was
      inoculated for 5 days with S. sanguis, and rats in group C and D were inoculated
      for 5 days with P. gingivalis. Group F served as a negative control. After
      inoculation, the levels of S. sanguis and P. gingivalis in the mouths of the rats
      were determined at 12 hours, 24 hours, 36 hours, 7 days, and 14 days. RESULTS:
      Both precolonization of S. sanguis and superinfection with S. sanguis reduced the
      level of P. gingivalis in experimental rats. However, the reduction was
      maintained for only 24 to 36 hours. The level of S. sanguis remained stable
      during the 14-days observation period. CONCLUSION: S. sanguis to function as the
      effector strain, the successful implantation of S. sanguis and the antagonistic
      action efficiently produced in vivo by S. sanguis is required.

PMID- 11314090
TI  - Evaluation of the new TAMZ titanium alloy for dental cast application.
AB  - OBJECTIVE: To reveal the potential of the new titanium alloy as dental
      prosthodontic materials. METHODS: Dental castings of TAMZ alloy were investigated
      in the casting machine specially designed for titanium. A mesh pattern was used
      to count the castability value. The mechanical properties were measured by means
      of a universal testing machine. Optical micrography was done on the exposed cross
      section of TAMZ alloy casting. From the surface to the inner part the Knoop
      hardness in reacted layer of TAMZ alloy casting was measured. The structure and
      elemental analyses of the reacted layer were made by SEM and element line
      scanning observation. RESULTS: The castability value (Cv = 98%) and the tensile
      test (sigma b = 850 Mpa, sigma 0.2 = 575 Mpa, delta = 7.33%) data were collected.
      The castings microstructure showed main alpha phase and small beta phase. Knoop
      hardness in the surface reacted layer was greater than that in the inner part.
      From the SEM and element line scanning observation, there are three different
      layers in the surface reacted layer of the TAMZ alloy castings, and higher level
      of element of O, Al, Si and Zr were found in the reacted layer while the Si
      permeated deeper than others. CONCLUSION: TAMZ alloy can be accepted as a
      material for dental alloy in prosthodontics.

PMID- 11314091
TI  - In vitro cytotoxicity evaluation of denture adhesive.
AB  - OBJECTIVE: The ideal denture adhesive demonstrates a minimal toxicity to the
      mucosa. The purpose of this study was to evaluate the in vitro cytotoxicity of a
      new denture adhesive. MATERIAL AND METHODS: Samples were prepared and extracted
      in Dulbecco's Modified Eagle's Medium. The cell viability of human oral
      fibroblast cells cultivated for 24 hours with DA-containing medium was evaluated
      by the MTT assay to investigate cell proliferation. Optical densities were
      measured by a spectrophotometer at 490 nm. RESULTS: The statistical analysis of
      results showed that this denture adhesive displayed only slight cytotoxicity.
      CONCLUSION: The generally favorable in vitro cytotoxicity of the denture adhesive
      formulation indicates that this product may be efficacious.

PMID- 11314092
TI  - Preliminary report on the effect of Nd: YAG laser irradiation on canine tooth
      pulps.
AB  - OBJECTIVE: To study the effects of Nd: YAG laser irradiation on the canine tooth
      pulps. METHODS: The crown pulp of dog was exposed and excised by ND: YAG laser
      irradiation. Histopathological examination was used to check changes of the
      tissues in root canal and periodontium. RESULTS: The pulp of the crown could be
      successfully excised by Nd: YAG laser without harmful changes in either root
      canal or periodontal tissues. CONCLUSION: This study may provide an experimental
      basis for the clinical possibility of crown pulp excision by using Nd: YAG laser
      irradiation.

PMID- 11314093
TI  - A real-time flat-panel X-ray pixel imaging system for low-dose medical
      diagnostics and craniofacial applications.
AB  - The aim of this study was to evaluate on-line performance of a real-time digital
      imaging system based on amorphous silicon technology and to compare it with
      conventional film-screen equipment. The digital detecting imager consists of (1)
      a converter, which transforms the energy of the incident X rays into light; (2) a
      real-time digital detecting system, capable of producing as many as 10 pictures
      per second using a large-area pixel matrix (20 x 20 cm2) based on solid-state
      amorphous silicon sensor technology with a pitch of 400 microns; and (3)
      appropriate computer tools for control, real-time image treatment, data
      representation, and off-line analysis. Different phantoms were used for
      qualitative comparison with the conventional film-screen technique, with images
      obtained with both systems at the normal dose (used as a reference), as well as
      with dose reduction by a factor of 10 to 100. Basic image quality parameters
      evaluated showed that the response of the detector is linear in a wide range of
      entrance air kerma; the dynamic range is higher compared with the conventional
      film-screen combination; the spatial resolution is 1.25 lp per millimeter, as
      expected from the pixel size; and good image quality is ensured at doses
      substantially lower than for the film-screen technique. The flat-panel X-ray
      imager based on amorphous silicon technology implemented in standard radiographic
      equipment permits acquisition of real-time images in radiology (as many as 10
      images per second) of diagnostic quality with a marked reduction of dose (as much
      as 100 times) and better contrast compared with the standard film technique.
      Preliminary results obtained with a 100-micron pitch imager based on the same
      technology show better quality but a less substantial dose reduction.
      Applications in craniofacial surgery look promising.

PMID- 11314094
TI  - Histomorphometry of parietal bones versus age and race.
AB  - Surgeons are used to obtaining bone grafts of calvaria, which are abundant and
      available. The outer table of the parietal bone can be split, usually at the
      level of the diploic interstice, with an osteotome. Inadvertently violating the
      inner table and the dura leads some surgeons to avoid using the outer table in
      the elderly. Sullivan and Smith measured the thickness of the outer tables,
      diploe, and inner table of 37 cadavers (average age, 59 years) and found each
      layer to be well preserved distinctly. However, they suggested that calvaria
      become brittle in patients older than 50 years of age. The current authors
      hypothesized that diploic composition is not changed, even in the elderly. The
      thickest part of the parietal bone of 49 Koreans and 30 whites were acquired, and
      undecalcified slides were made. Via light microscopy, using the National
      Institutes of Health image, the following measurements were made: the thickness
      of the parietal bone (PT), outer table (OT), diploe (DT), and inner table (IT);
      trabecular bone volume percent (TBV); trabecular thickness (TT); and trabecular
      separation (TS). There was no significant difference in the thickness of the OT,
      DT, and IT of the PT, TBV, TT, and TS among different ages. The PTs of women were
      thicker than men's. The PTs of whites were significantly thicker than Koreans'.
      This study disclosed that the DT is not different among varying age groups and is
      not sclerosed in the persons older than 80 years, and the OT of these individuals
      is not brittle. Thus, surgeons do not need to hesitate when taking the OT of the
      PT in older patients. However, the selection of the site is attentive to PT. The
      thickest posteromedial part of the PT is favorable and safe as a donor.

PMID- 11314095
TI  - The use of bone morphogenetic protein gene therapy in craniofacial bone repair.
AB  - Bone morphogenetic proteins (BMPs) are capable of inducing endochondral bone
      formation when applied on biologic carriers in numerous mammalian in vivo assay
      systems. Bone morphogenetic protein gene therapy is also currently being
      developed to promote osteogenesis for clinical indications such as spinal
      fusions, craniofacial bone loss, and osteoporosis. In this study, critical-sized
      mandibular defects were treated with a control adenoviral vector (Ad-beta-gal), a
      BMP-2 adenoviral vector (Ad-BMP-2), or a BMP-9 adenoviral vector (Ad-BMP-9).
      Gross tissue examination, radiographic analysis, and histologic analysis
      demonstrated significant bony healing in the BMP treated groups compared to
      controls. Osteogenesis was limited to the bony defect, without extension into the
      surrounding soft tissues. The study suggests that with further development, BMP
      gene therapy may be potentially useful for repair of bony defects in the
      craniofacial region.

PMID- 11314096
TI  - Ethics and craniofacial surgery.

PMID- 11314097
TI  - The reliability and variability of SN and PFH reference planes in cephalometric
      diagnosis and therapeutic planning of dentomaxillofacial malformations.
AB  - Various interpretations of clinical and cephalometric data lead to different
      diagnostic and surgical planning in the study of dentoskeletal malformations.
      Many authors have identified this discrepancy as an incorrect positioning between
      the skeletal structures and the Frankfurt plane (PFH)--a plane that is used
      routinely for the sagittal measurement of the upper and lower jaw. The aim of
      this study was to establish a control method to verify the correct positioning of
      the sella-nasion point plane (SN) and the PFH. To find a reference plane, the
      authors concentrated their attention on measuring the intersecting angles between
      these two planes and the vertical posterior maxillary (PM) plane. Fifty patients
      (33 women and 17 men), all of whom were aesthetically and structurally harmonious
      class I dentoskeletal types, were analyzed using this method. Student's t-test,
      the Kolmogorov-Smirnov test, and Fisher's F-test were used for statistical
      analysis. The results were compared with those proposed by the University of
      Michigan. To achieve a correct diagnosis and to obtain good functional and
      cosmetic results in the treatment of these kinds of malformations, it is
      necessary to make use of the PM vertical plane during cephalometric analysis.

PMID- 11314098
TI  - Brachycephaly and external pressure.
AB  - Browsing through some literatures, I happened to find out some records on the
      rite of imitation of the child's head to brachycephaly. In 1976, two skulls
      showing extraordinary forms were excavated out of an ancient tomb at Yean village
      of Daedong township in Kimhae County in Kyungnam Province, the Republic of Korea.
      The deformation in Yean village is judged to be an intentional frontal
      flattening. The frontal bone of deformed individuals is remarkably flattened by a
      primary deforming force. The parietal bone expands laterally and
      superoposteriorly as a major compensatory growth. The lambdoid or occipital
      flattening induced by the counterforce is light and unstable. In the facial
      skeleton, the maxilla shifts downward as a minor compensatory growth. These
      findings might be substantially correspondent to the custom in the southern area
      of Korea in the 4th century A.D. paragraphed by Han chuan of Wei-dynasty record,
      History of the Three Kingdoms. It described that the people gave a pressure onto
      the child's forehead with stones in order to mold it for preference. Flatheaded
      meant "free" among the Chinook and Salish tribes of American Indians. Babies of
      slaves were denied the year-long beauty treatment--a board tied to the infants'
      padded skull--that permanently flattened the foreheads of tribal members.
      Referring to these records, I presume that brachycephaly can be induced by direct
      extrinsic pressure at least until the soft infant's head gets hard.

PMID- 11314099
TI  - Surgical removal of intra- and extraoral cavernous lymphangiomas using
      intraoperative-assisted intralesional fibrin glue injections.
AB  - Benign lymphangiomas are encountered frequently in the head and neck region. They
      may be well circumscribed or diffusely invasive, involving subcutaneous tissue
      and underlying muscle, and consist of dilated, thin-wall sinuses. Surgical
      therapy with excision as wide as possible, while taking care to avoid rupturing
      the lesion, is the treatment of choice. To simplify complete excision, the
      authors introduce an intraoperative technique--intralesional injection of fibrin
      glue. Using this technique over period of 10 years in 27 patients (age range, 7
      24 years) they removed successfully intra- and extraoral lymphangiomas. There
      have been no recurrences. This technique helps avoid rupture of the epithelium
      and bleeding, and makes it easier to remove lymphangiomas surgically and as
      completely as possible. This technique reduces recurrence remarkably and ensures
      successful surgical excision.

PMID- 11314100
TI  - Hemimandibular hyperplasia: treatment strategies.
AB  - Hemimandibular hyperplasia is a well-defined, rare asymmetrical mandibular
      malformation. It is characterized by diffuse enlargement of the condyle, the
      condylar neck, and the ramus and body of the mandible. Because the anomaly begins
      before puberty, it is understandable that the maxilla follows the downward growth
      of the mandible. Pathogenesis is due most likely to clear hyperactivity in the
      condyle, which can be documented histologically with an actively proliferating
      cartilage. Therapy is largely based on the patient's age. The authors present
      their series of nine individuals with hemimandibular hyperplasia treated with
      various surgical methods between 1992 and 1994. A therapeutic approach called
      orthopedic maxillary management applied to two of the nine patients is presented.
      The objective is to maintain the occlusal maxillary plane in a correct position
      in growing patients. All clinical results, except one, were satisfying and showed
      good postoperative stability.

PMID- 11314101
TI  - A rat model of gingivoperiosteoplasty.
AB  - The ability to avoid a subsequent bone graft makes the use of
      gingivoperiosteoplasty (GPP) at the time of cleft lip repair an attractive
      technique. The use of GPP, in combination with presurgical orthodontics, has been
      shown to result in successful bony union in the majority of patients. However,
      secondary bone grafting is still necessary in 30% to 40% of patients due to
      persistent alveolar bony defects. The elucidation of methods to improve the
      success rates of these procedures has been hampered by the lack of reproducible
      animal models. The purpose of this study was, therefore, to develop a rodent
      model of GPP that would facilitate the investigation of methods to improve
      osteogenesis in alveolar defects. We report a surgically produced rat model (9 x
      5 x 3-mm alveolar defect) that is reproducible, inexpensive (relative to large
      animal models), and simple technically. In addition, healing in this model occurs
      in a predictable manner during a 12-week period, thus enabling analysis of
      methods designed to accelerate or facilitate osseous regeneration.

PMID- 11314102
TI  - A submerged osteodistraction device: an innovative technique for experimental
      animal studies.
AB  - The author presents a submerged mandibular distraction device that can be used in
      the rabbit mandible for additional experimental studies of the distraction
      osteogenesis process. A distractor to suit the rabbit mandible was designed by
      the author. It is fixed to the mandible under layers of skin and mucoperiosteum.
      It can distract both sides of the mandible simultaneously without the need for
      two separate devices. The body of the distractor is 1.5 x 1.0 cm, and the total
      length is 3 cm. It weighs 2 g.

PMID- 11314103
TI  - New refinements in controlled depth osteotomy (CDO).
AB  - To enhance the safety of the patient a controlled depth (CD) osteotomy cutter was
      designed. The power-oriented depth controlled osteotomy cutter (PODCO) was
      developed and used in patients and infants craniofacial surgery. As the power
      equipment was technologically advanced, a new design allowed us to keep the same
      principle with a technologically advanced cutter. The new 1 mm cutter allows the
      surgeon to dial in the desired depth so that the osteotomy can be performed with
      precision and enhanced safety to the patient.

PMID- 11314104
TI  - Alloplastic tumor of the palate: view from the operating room.

PMID- 11314105
TI  - Cleft palate: modern technology and neuroscience merge.
AB  - This is a report of a cleft palate-craniofacial team's experience with 768
      patients that have had clefting over 22 years, with a primary focus on function
      and prevention of communication disorders associated traditionally with cleft
      palate. The treatment philosophy is based on tenets of child development and the
      dependency of neuropsychobiological development on the child's inherent
      competency, and early environmental stimulation and support. The applied
      treatments include ensuring early and adequate hearing, psychosocial adaptation
      of the parent and child through training for applications of indirect therapies,
      and early fistula-free surgical closure of the cleft that produces minimal
      scarring and a mobile velum. Team members have extensive backgrounds in child
      development that seem to have helped the majority of families in their complex
      efforts of daily care and sensory stimulation, and their children have developed
      early the ability to adapt modified structures to normal functions. Only one of
      these patients has needed or received secondary palatal surgery for correction of
      velopalatal insufficiency. Fifty-six children who did not achieve acceptable 2 to
      3-year old communication criteria were referred for speech and language
      evaluation and therapy. These patients were reported to exhibit oral motor
      deficits described as developmental verbal dyspraxia.

PMID- 11314106
TI  - Inheritance of Hippel-Lindau disease: a rare case of maxillary bone metastasis.
AB  - A rare case of familial Hippel-Lindau disease, which is an autosomal dominant
      disorder with inherited susceptibility to various forms of cancer, is reported in
      a 46-year-old father and his sons. The father complained of a malignant
      hypernephroma, which metastasized in the upper jaw 6 months later. As in this
      patient, renal cell carcinomas are fatal and are exhibited at an early age.
      Consequentially, patients with familial von Hippel-Lindau disease exhibiting
      cases of renal cell carcinoma should be examined very carefully in the head and
      neck region to detect and treat metastases as early as possible.

PMID- 11314107
TI  - Salivary markers: their role in breast cancer detection.

PMID- 11314108
TI  - Broad support evident for the emerging specialty of orofacial pain.
AB  - The emerging field of Orofacial Pain is being considered by the American Dental
      Association for full status as a new dental specialty. Many recent advances in
      the neuroscience of orofacial pain have lead to treatments by orofacial pain
      dentists that provide significant relief for patients with chronic orofacial pain
      disorders. However, access to this care has been limited leaving many patients to
      continue to suffer. Subsequently, recent efforts to improve this by developing
      the field into a specialty have shown broad support among dentists and increased
      awareness of the benefits this field can provide for dentists and their patients.
      A recent survey of 805 individuals in the general population who reported having
      a persistent pain disorder revealed that more than four out of 10 people have yet
      to find adequate relief, saying their pain is out of control-despite having the
      pain for more than 5 years and switching doctors at least once. "This survey
      suggests that there are millions of people living with severe uncontrolled pain,"
      says Russell Portenoy, MD, President of the American Pain Society. "This is a
      great tragedy. Although not everyone can be helped, it is very likely that most
      of these patients could benefit if provided with state-of-the-art therapies and
      improved access to pain specialists when needed." (1). Development of the field
      of Orofacial Pain into a dental specialty has been motivated primarily by this
      issue; patients with complex chronic orofacial pain disorders have not been
      historically treated well by any discipline of health care. Recent studies of
      chronic orofacial pain patients have found that these patients have a high number
      of previous clinicians and have endured many years with pain prior to seeing an
      orofacial pain dentist (2) (Fig. 1). Complex pain patients and the clinicians who
      see them are often confused about whom they should consult for relief of the
      painful disorder. Treatment for these patients within the existing structure of
      dental or medical specialties has been inadequate and millions of patients are
      left suffering. Insurers are also confused with regard to reimbursement and make
      decisions to exclude treatment for orofacial pain disorders under both dental and
      medical policies. However, Dentistry has taken a leading role in health care to
      address this national problem by developing the field of Orofacial Pain into a
      dental specialty. A study of dentists and dental specialists have shown that
      there is a recognized need and broad support for further development of this
      field into a new dental specialty(3).

PMID- 11314109
TI  - Fluoride concentrations in bottled water.
AB  - Bottled water use and lack of adequate labeling have given rise to questions
      regarding fluoride intake. This study examined fluoride concentration of
      commercially available bottled water products, determined if significant
      differences existed among the products, and explored packaging date as a variable
      on the concentration of fluoride. The values were compared to the ADA guideline
      for optimally fluoridated water and the American Academy of Pediatric Dentistry
      recommended schedule for fluoride supplementation. Five commercial brands were
      chosen for the study. Three bottles of each brand, each with different batch
      dates, were purchased. Following calibration, six tests were conducted on each
      bottle using the Hach DR-100 Colorimeter System for fluoride analysis and the
      values were recorded. Data were analyzed using a two-tailed ANOVA and Tukey's HSD
      Test (p = 0.05). The results showed that significant differences in fluoride
      concentrations existed among the five brands. For three brands, significant
      differences existed between the batches. All products had fluoride concentrations
      that fell below the ADA accepted standards for optimally fluoridated water. Due
      to the significant variability in fluoride concentration between products and
      batches, dental providers should advise their patients that bottled water might
      not contain optimal levels of fluoride.

PMID- 11314110
TI  - Do you believe in managed care?

PMID- 11314111
TI  - What will the future hold?

PMID- 11314112
TI  - Intensity of curing lights affected by barriers.
AB  - PURPOSE: Infection control with the use of curing lights is a problem for many
      oral health care offices. The purpose of this study was to determine if the use
      of protective barriers with curing light tips would affect the intensity of the
      light output of commercial light curing units as measured by a commercial
      radiometer. METHODS: Four different disposable barriers were tested on four light
      curing units to determine light intensity output (mW/cm2). Three readings of
      light output for each light source were obtained in each case and means and
      standard deviations were calculated. Means comparison was performed using
      analysis of variance and Tukey-Kramer intervals at the .05 significance level.
      RESULTS: The factors of barrier (p = .001) and light curing unit (p = .0001) were
      significant. The interaction (p = .54) was not significant. Light intensity
      output decreased significantly with addition of every barrier, except for the
      Sani-Shield barrier with all the light units tested, and Protectop barrier with
      the Coltolux 4 unit. The greatest reductions occurred with the addition of the
      All Purpose Adhesive Covering barrier to all light units except the Dentsply
      (glass tip), and with the Protectop barrier to the Dentsply light unit (glass
      tip). CONCLUSIONS: Barrier protection can be used with curing light tips only
      after determination that the emitted light intensity output is adequate.

PMID- 11314113
TI  - A proposed client self-care commitment model.
AB  - PURPOSE: Expansion of the dental hygiene body of knowledge offers options for the
      profession; evolving conceptual models allow practitioners to choose an approach
      to client care that is scientifically sound yet matches individual philosophies.
      Health paradigms for different approaches to client care have been developed and
      used in medical anthropology, psychology, and dental hygiene. Adapted from the
      biomedical model, the explanatory model, the empowerment model, and the human
      needs conceptual model, a new model for client commitment is proposed. The client
      self-care commitment model is composed of five domains: initiation, assessment,
      negotiation, commitment, and evaluation. This model proposes that the
      relationships among these domains, and the interaction between the client and the
      dental hygienist can empower clients to make decisions that will enhance their
      own health through commitment and compliance. This paper reviews the scientific
      literature from medical anthropology, psychology, and dental hygiene that focus
      on client care, and suggests possible applications of the model to the dental
      hygiene process of care, dental hygiene education, and qualitative research.

PMID- 11314114
TI  - Handpiece sterilization.

PMID- 11314115
TI  - Sugar replacers and the FDA noncariogenicity claim.
AB  - In 1996, the U.S. Food and Drug Administration (FDA) approved the use of a
      "health claim" based on the association between sugar replacers and the
      nonpromotion of dental caries. Small packages of products containing such
      sweeteners may state "Does not promote tooth decay" or "May reduce the risk of
      tooth decay." Larger packages must include additional information, such as
      "Frequent eating of foods high in sugars and starches as between-meal snacks can
      promote tooth decay." FDA criteria state that these products must not only be
      "sugar-free," but they must also contain a noncariogenic sugar replacer and not
      lower plaque pH below 5.7 either during consumption or up to 30 minutes after
      consumption when tested by in vivo pH telemetry. Many people might reduce their
      caries risk by using sugar-free products, and the FDA claim can help consumers
      identity such products. Dental hygienists are ideal sources of consumer
      information about sugar replacers, and can help clients distinguish between the
      new FDA claim and advertising claims that are not regulated by FDA. The purpose
      of this article is to provide dental hygienists with information on sugar
      replacers that will help clients make appropriate nutrition choices.

PMID- 11314116
TI  - Controlling dental hygiene work-related musculoskeletal disorders: the ergonomic
      process.
AB  - Work-related musculoskeletal disorders (WMSDs) have been reported frequently by
      dental hygienists. The practice of dental hygiene exposes practitioners to WMSD
      risk factors of repetitive motion, pinch-grasp, force, vibration, and prolonged
      awkward positions. The objective of an ergonomic program is to fit the job to the
      worker, rather than the worker to the work. Principles of the ergonomic process
      can be applied in private dental practice to design a program that meets the
      needs of each practitioner. The ergonomic process includes data collection,
      assessment, the ergonomic plan itself, and evaluation of strategies. The worker
      (dental hygienist), work processes, and the work environment are integral parts
      in the ergonomic process. The purpose of this article is to provide basic
      information on the ergonomic process so that individuals can develop a program
      that meets their need to reduce WMSDs.

PMID- 11314117
TI  - Women and tobacco: oral health issues.
AB  - As a female-dominated profession, dental hygiene has a heightened interest in
      women's health issues. An area of disease prevention and health promotion that
      merits gender specific interventions is tobacco use. Tobacco initiation,
      habituation, and cessation are different for men and women, and their effects on
      women's health also are more varied and unique. This paper addresses trends in
      tobacco use by women, gender specific developmental and sociocultural
      considerations in initiation and habituation; the pregnant tobacco user and the
      developing fetus; menopause, osteoporosis, heart disease, and tobacco use; the
      economic impact of pregnancy and tobacco use; and successful interventions with
      women who use tobacco. Since women present for more dental office visits than
      males, female patients are more accessible to the dental hygienist's tobacco
      intervention message, and gender specific strategies may be most successful.
      Dental hygienists' strong counseling and motivational abilities, along with their
      inherent interest in women's issues, can make prevention and cessation activities
      with female patients who use tobacco both challenging and rewarding.

PMID- 11314118
TI  - Thoracic outlet syndrome.

PMID- 11314119
TI  - Managing the side effects of medications.
AB  - Dental hygienists learn of the drugs taken by clients by conducting thorough
      comprehensive health history and pharmacologic history reviews. Many clients take
      multiple medications; therefore, dental hygienists must be aware of the issues
      related to drug use, including indications, interactions, and adverse drug
      effects. The ability to evaluate these issues is necessary to accurately assess
      client status and prevent situations that compromise client safety. Oral side
      effects are adverse effects that interfere with client function, and increase
      risks for infection, pain and possible tooth loss. The purpose of this continuing
      education course is to review adverse drug effects and to discuss appropriate
      dental hygiene interventions used to manage oral complications associated with
      commonly prescribed medications. Dental hygienists will learn to accurately
      diagnose oral complications of medication use, and make appropriate treatment
      recommendations to manage these effects. Timely recognition and professional
      interventions are necessary to improve client comfort and maintain oral health
      and function. Successful completion of the course objectives will be assessed by
      a post-test, to be completed by the learner after reading the article in its
      entirety. Two hours of continuing education course credit will be awarded
      following successful completion of the post-test.

PMID- 11314120
TI  - Thoracic outlet syndrome.

PMID- 11314121
TI  - Gene mutation leaves people susceptible to gum disease.

PMID- 11314122
TI  - Congenital teratoma of the oropharyngeal cavity with intracranial extension: case
      report and literature review.
AB  - Congenital teratoma of the oropharyngeal cavity is a unique clinical entity that
      poses immediate threats to the neonate in the postpartum period. Establishment of
      a secure airway is a primary goal after delivery; complete surgical resection is
      the subsequent guiding principle of management. Even more rare than teratomas
      confined to the oropharynx are tumors that extend into the intracranial cavity
      during development. Descriptions of these lesions in the medical literature are
      uncommon. In the majority of these reports, the tumors are associated with
      stillbirth, perinatal death, or significant morbidity after attempted resection.
      We present the rare case of a patient with congenital oropharyngeal teratoma with
      intracranial extension who has demonstrated long-term survival without any
      neurological or functional deficits. A unique delayed staged approach to
      resection of the extracranial and intracranial components of the tumor is
      described.

PMID- 11314123
TI  - Treatment of micrognathia with edentulous maxilla by sagittal split mandibular
      osteotomy and a subperiosteal implant immobilized with transmaxillary screws.
AB  - Micrognathia complicated by edentulous maxilla was treated by performing sagittal
      split mandibular osteotomy and immobilizing a subperiosteal implant using
      transmaxillary screws. The patient was a 42-year-old man who had a birdlike
      facial deformity caused by significant hypoplasia of the mandible. He also
      demonstrated significant malocclusion attributable to micrognathia and edentulous
      maxilla caused by resorption of the alveolar bone. These conditions impaired his
      mastication and articulation, making it impossible for him to eat regular food or
      carry out normal conversation. A subperiosteal implant was placed on the
      edentulous maxilla, and was rigidly immobilized to the maxilla using five
      transmaxillary screws. A prosthesis was then attached to the implant, and by
      using the implant as the point of reference and the anchor, the mandible was
      moved forward by sagittal-split mandibular osteotomy. Intermaxillary fixation was
      subsequently performed. The postoperative course has been favorable, and his
      facial complexion has improved significantly. One and a half years after his
      surgery, there has been no sign of complications or malocclusion caused by
      mandibular retraction. He is now able to eat regular food and speak normally.

PMID- 11314124
TI  - Maxillary distraction osteogenesis: a method with skeletal anchorage.
AB  - Maxillary distraction osteogenesis is a challenging technique to treat severe
      maxillary retrusion. Maxillary advancement by distraction has the advantage to
      provide new bone in combination with simultaneous expansion of the soft-tissue
      functional matrix. Cleft lip and palate patients can present with severe
      maxillary retrusion and Class III malocclusion. Two 13-year-old patients, born
      with non-syndromic cleft lip and palate, underwent maxillary distraction--one had
      a bilateral, the other a unilateral complete cleft lip and palate. Maxillary
      advancement was performed using an external distraction device in combination
      with titanium miniplates as a skeletal maxillary anchorage. After a complete
      Lefort I osteotomy with pterygomaxillary disjunction, a latency period of 3 days
      was respected. On the fourth postoperative day, distraction was initiated at the
      rate of 1 mm/d. Preoperative clinical photographs, dental casts, lateral
      cephalograms, and panoramic radiographs were taken. Further lateral cephalograms
      were obtained after the latency period, after completion of the active period of
      distraction, at the completion of the consolidation period, and at 6 and 12
      months postoperatively. The aesthetic outcome was excellent and skeletal
      advancement of 8 and 7 mm was measured without dentoalveolar compensations.

PMID- 11314125
TI  - One-stage approach to the correction of facial skeletal deformity with
      malocclusion.
AB  - A total of 40 patients with varying degrees of facial skeletal deformity and
      Class III malocclusion were treated by bimaxillary osteotomy combining maxillo
      malar augmentation and/or osseous genioplasty at the same sitting by the author.
      In all patients, the maxillary advancement and mandibular set back were
      performed, using Le Fort I maxillary osteotomy and bilateral sagittal split
      osteotomy of the mandibular rami. In additional bimaxillary osteotomy,
      simultaneous maxillo-malar augmentation and genioplasty in 20 patients,
      genioplasty in 12 patients, maxillo-malar augmentation in eight patients, were
      performed to improve facial harmony. All patients were followed clinically and
      radiographically for at least 1 year and as much as 5 years after undergoing
      surgical correction. No cases with relapse or other major complications have been
      encountered up to now. There were, however, persisting unilateral inferior
      alveolar nerve damage in two patients, prolonged nerve anesthesia or hypoesthesia
      in four patients, and short period anesthesia or hypoesthesia in 11 patients,
      wide alar base in three patients and slight deviation of cartilage septum in two
      patients. There were no other complications encountered and an unexpected result.
      The facial skeletal deformity and malocclusion were always treated satisfactorily
      as patient and plastic surgeon's expectations in one-stage operation, without
      significant complications and morbidity.

PMID- 11314126
TI  - Correction of the bilateral cleft using the sliding sulcus technique.
AB  - The morphology of the bilateral cleft lip can be understood in terms of process
      theory and field theory. The former holds that an initial event sets in motion
      processes of division, deficiency, displacement, and distortion; these act on the
      cleft site to convert a trivial defect into the final result seen at birth. Field
      theory describes embryonic units that are in disarray by virtue of the cleft. A
      subperiosteal technique is described that combines these concepts to achieve
      simultaneous closure of the lip and alveolus. Primary separation of the nasal tip
      from the philtral-columellar unit is carried out along embryonic fusion lines.

PMID- 11314127
TI  - Complications in craniofacial surgery: the Turkish experience.
AB  - The records of 71 patients who underwent 75 consecutive craniofacial procedures
      involving a transcranial component have been analyzed retrospectively to assess
      the incidence and type of complications encountered during the 14-year period of
      1985 to 1998 at Ege University Hospital, Department of Plastic and Reconstructive
      Surgery. The results were compared with those of similar reports from other
      craniofacial centers. Operations were classified into six groups according to
      their type to evaluate effectively their complication rates. Complications were
      also graded in terms of their severity. Serious complications were seen in 12
      patients (16.8%), whereas life-threatening complications were seen in 6 patients
      (8, 4). The mortality rate was 2.7%. It is determined that complication incidence
      was notably higher in the group that underwent monobloc frontofacial advancement.
      A decrease in the rate of serious complications occurred with increased
      experience with the surgery. The results of our study indicate that although
      craniofacial surgery carries an inherent risk for significant complications, the
      risk can be minimized and the rate of mortality and major complications kept to
      an acceptable level by a careful and experienced craniofacial team.

PMID- 11314128
TI  - Application of the distraction technique to scaphocephaly.
AB  - The case of a 1-year-old boy who underwent correction of a scaphocephalic
      deformity using distraction devices is described. Double pi-shaped osteotomies
      were cut. Bilateral temporal bone flaps were gradually expanded, and the frontal
      bone was pulled back simultaneously. The patient showed a good skull contour 2
      years postoperatively. Although previous distractions were aimed only at
      expansion of the cranium, we used the distraction technique to successfully
      shorten the cranial vault in the anteroposterior direction. This case
      demonstrates that the osteotomized bone flaps can be moved in various directions.
      This feature of the distraction technique may contribute greatly toward
      meticulous reconstruction of the cranial vault.

PMID- 11314129
TI  - An assistive device for the treatment of positional plagiocephaly.
AB  - An assistive device (AD) was used to treat 122 infants with moderate-to-severe
      positional plagiocephaly. Clinical evaluations indicate that the AD provided the
      most benefit when applied to 2- to 8-month-old children. Our results suggest that
      the AD may join molding helmets and physical therapy as a treatment for moderate
      to-severe positional plagiocephaly in infants under the age of 1 year.

PMID- 11314130
TI  - Interface between titanium miniplate/screw and human calvaria.
AB  - This study demonstrates interfacial changes of titanium miniplate/screw with
      normal calvaria and nonvascularized calvarial bone graft ensued from craniectomy
      in a 53-year-old female. In 18 months after operation, a right parietal bone
      containing an L-shaped miniplate with screws, 5 mm long and 2 mm in external
      diameter, was harvested, fixed, and embedded in methylmetacrylate. Fifteen
      micrometer thick sections were made by an EXAKT cutting-grinding system (Exakt
      Company, Hamburg, Germany), and reviewed under the bright field light microscope.
      The mean of the bone-contacting surface ratio (BCSR) in six screwed bone was
      64.1%; 69.3% in normal bone, and 60.4% in grafted bone. The trabecular bone areas
      in 10 x 5 mm (50 mm2) rectangular area of diploe surrounding the screws was 43.02
      mm2; 45.25 mm2 in normal calvaria; and 41.82 mm2 in grafted bone. The mean Ca/P
      peak-height ratio of the plated and screwed calvaria was 1.47 in a 9 mm wide zone
      around each screw; 1.37 in normal calvaria; and 1.51 in grafted calvaria. We
      concede that the effect of direct contact of titanium with screws onto the bone
      is as much as an osseous integration (osseointegration).

PMID- 11314131
TI  - Study on the secretion of cytokines from osteoblasts stimulated with
      prostaglandin E1.
AB  - In previous studies, prostaglandin (PG) E1 was found not only to enhance the
      effect of rhBMP, but also to increase orthotopic osteoconduction and enhance bone
      formation, even when used alone, as well as increasing the physical strength of
      implanted porous hydroxyapatite ceramics (HAP). In the present study, the
      secretion of cytokines from MC3T3-E1 cells was investigated, which is a cell line
      of osteoblasts derived from the mouse skull, stimulated in vitro by 10(-5) M and
      10(-6) M PGE1, in order to elucidate the mechanism of action of PGE1. The
      cytokines examined included transforming growth factor (TGF) beta 1, interleukin
      (IL)-6, and IL-1 beta. The results of this study clarify the mechanism of
      enhancement of osteogenesis by PGE1. Elevated TGF beta 1 plays a very important
      role, and the findings are significant because they may provide the basis for the
      establishment of a rational clinical combined application of these materials.

PMID- 11314132
TI  - Tension forces in relation to LeFort III osteotomies.
AB  - Complications associated with LeFort III osteotomies have led to modifications of
      the procedure. Attempts to decrease morbidity include performing incomplete
      osteotomies or eliminating pterygomaxillary dysjunction. The purpose of this
      study was to determine the amount of tension required for separation of the
      midface from the pterygoid plates and to observe the fracture patterns. An
      Instron machine (Instron Corporation, Canton, MA) was used to measure the tension
      forces in 16 cadaver skulls divided into five groups. The groups varied as to
      whether the osteotomies were complete and whether pterygomaxillary separation was
      performed. Specimens with incomplete osteotomies and without pterygomaxillary
      separation required greater tension forces for separation and exhibited a high
      percentage (47%) of unfavorable fractures. Because high amounts of tension are
      required leading to unpredictable separations, we recommend complete osteotomies
      with pterygomaxillary dysjunction when performing LeFort III osteotomies.

PMID- 11314133
TI  - Another day to remember.

PMID- 11314134
TI  - Comparison of the morphology of the "cleft face" and the normal face: defining
      the anthropometric differences.
AB  - Morphological characteristics of the "cleft face" were analyzed by calculating
      proportion indices in young adults who had undergone surgery in childhood for
      cleft lip and/or palate: 592 in 37 subjects with unilateral clefts and 432 in 27
      with bilateral clefts. Three areas of the face with 16 indices based on 12
      projective linear measurements were analyzed in each subject: 5 indices in the
      general face, 6 in the upper face, and 5 in the lower. Although a balanced
      relationship was found in two thirds of the indices assessed, severe
      disproportions, which greatly influence appearance, were noted in about one
      quarter. In the general face, the most frequent abnormal anthropometric findings
      contributing to severe disproportions were small upper-face height and a severely
      high or moderately narrow mandible. In the soft tissues, disproportions included
      wide nose, small nasal tip protrusion, and short or long columella. Deviations
      from normality were rarely noted in the nose and upper-lip height, mouth width,
      total facial height, and width of the upper face. In the upper face, severe
      disproportions occurred much more frequently in bilateral cleft subjects (67.6%)
      than in unilateral clefts (30.3%). In the lower face, however, severe
      disproportions were twice as frequent among unilateral clefts (39.4%) than
      bilateral (14.7%). The results, although interesting, require complementary
      preoperative data for reliable analysis of the adult "cleft face."

PMID- 11314135
TI  - Controlled multiplanar distraction of the mandible. Part III: Laboratory studies
      of sagittal (anteroposterior) and horizontal (mediolateral) movements.
AB  - Distraction osteogenesis has proven to be an effective technique for the
      correction of mandibular deficiencies. However, problems have been encountered in
      achieving a final, idealized form of the mandible when using distraction devices
      capable of moving the bone segments in only one dimension (uniplanar).
      Specifically, occlusal irregularities and deficiencies in lower facial contour
      have been seen following uniplanar distraction. To address these problems, a
      distraction device capable of independent movements in three planes (multiplanar)
      was developed. Previously reported studies in a canine model have demonstrated
      that this device can successfully distract the mandible along both the sagittal
      axis (anteroposterior or z-axis) and the vertical axis (superoinferior or y
      axis). This study examines the ability of the multiplanar device to distract
      along the sagittal and horizontal axes (mediolateral or x-axis). A total of 12
      dogs were included in the study. All animals underwent unilateral or bilateral
      mandibular distraction using an external multiplanar device. After a latency
      period of 5 days, primary distraction along the anteroposterior axis at a rate of
      1 mm/day for 10 days (10 mm total) was performed. During the following 10 days,
      along with an additional 11 mm to 20 mm of anteroposterior axis distraction,
      concomitant secondary distraction was performed along the horizontal
      (mediolateral) axis at a rate of 5 degrees/day (50 degrees total). Cephalometric
      radiographs were obtained preoperatively and at the conclusion of both
      anteroposterior and combined anteroposterior-mediolateral distraction. Computed
      tomography (CT) scans were obtained preoperatively and at the end of
      consolidation (28 days), after which all animals were sacrificed and the dry
      skulls examined. In all animals, distraction along the mediolateral or x-axis was
      found to change the anteroposterior projection of the mandible. Varus angulation
      of the device with respect to the midline of the mandible caused compression of
      the distracted segments and reduced the anteroposterior thrust of the mandible.
      In contrast, valgus positioning of the device, with respect to the midline of the
      mandible, created the opposite effect, increasing the distracted length in the
      anteroposterior direction. The bone (mandibular) segments being distracted
      assumed the orientation of the device only for valgus positioning of the device
      (producing a decrease in the bigonial distance). Conversely, there was no effect
      from the mediolateral angulation on the distracted segments during varus
      positioning of the device. A possible explanation for this finding may be a
      greater resistance to an increase in the bigonial distance (varus positioning of
      the device) posed by obstruction of lateral movement of the condyle. This stands
      in contrast to a decrease in the bigonial distance observed following valgus
      positioning of the device. These findings confirm the clinical impression that
      distraction along the anteroposterior or sagittal axis remains the critical or
      keystone therapeutic maneuver in distraction of the mandible. Mediolateral or
      horizontal axis distraction is best used only as a supplementary movement; in
      essence, it only affects the anteroposterior dimension with little impact on
      clinically relevant changes to the bigonial distance.

PMID- 11314136
TI  - Priorities in the treatment of facial fractures for the millennium.
AB  - Although certain principles for management of facial fractures have not changed,
      new avenues reach this goal with greater precision and less morbidity. By
      reviewing these recent developments one can see the enormous potential for future
      developments in technology, techniques, and biomaterials. Development of tertiary
      care centers for the multiple trauma victim has improved management of facial
      trauma by bringing a large experience to a team of individuals where creativity
      flourishes. Major leaps in diagnostic skills and technology now allow us to
      answer some to the controversial treatment issues in facial trauma. This article
      hopes to review some old concepts and look at new approaches in managing facial
      fractures.

PMID- 11314137
TI  - Surgical solutions to periodontal complications of orthodontic therapy.
AB  - Collaboration of various specialists has become essential in pediatric dental
      practice. In orthodontics, this collaboration is completely necessary when the
      patient presents periodontal problems. Even in healthy patients, who do not
      suffer from periodontal disease, periodontal complications may occur during
      treatment with fixed appliances. Two cases of young patients, in which
      periodontal procedures were used to complement the results of orthodontic
      treatment are presented.

PMID- 11314138
TI  - Correction of posterior crossbite in the primary dentition.
AB  - This study shows the types of malocclusions that can be treated in the primary
      dentition and advocates correction of maxillary constrictions from five years of
      age onwards, when such constrictions lead to crossbites. A preferred method to
      treat maxillary constrictions is through rapid maxillary expansion (RME) with the
      Haas expander, even in the early stages of occlusal development. This paper
      presents a cross-sectional evaluation and a long-term follow-up of the upper
      permanent incisors during the active and passive phases of RME and shows no signs
      of root or pulp alterations.

PMID- 11314139
TI  - Treatment of anterior crossbite with bilateral posterior crossbite in early mixed
      dentition: a case report.
AB  - A case report of a 7-year-old boy who had Class III skeletal pattern is
      presented. The maxilla was deficient in anteroposterior and transverse
      dimensions, causing a slightly concave profile, a crossbite relationship of most
      of the anterior and posterior teeth, and upper anterior crowding. The rapid
      palatal expansion therapy effectively uprighted the posterior segments and
      developed the arches. Alignment, leveling and development of a good functional
      occlusion was accomplished with the .022" x .028" standard edgewise appliance.

PMID- 11314140
TI  - Pacifier-sucking associated with a bizarre habit: a case report.
AB  - A case of a child, who used the pacifier with an uncommon habit is presented. She
      pulled out the hair on the right side of her head after rolling it round the base
      of the pacifier. She then sucked it and swallowed it. Based on this report the
      authors are emphasizing the importance of accompanying the orofacial development
      of the child as from its first year of life.

PMID- 11314141
TI  - The relation of bruxism and dermatoglyphics.
AB  - With the aim to examine the dermatoglyphic patterns of finger and palm, 38
      bruxism patients, 18 being female were studied. Fingerprint patterns in bruxism
      has previously been discussed in a few papers, but this is the first paper about
      dermatoglyphic patterns of palm in bruxism. The aim of this study of finger and
      palm prints in patients with bruxism were to discuss the importance of
      dermatoglyphic patterns in the diagnosis and etiology of the disease. Bruxism
      patients demonstrated an increase in frequency of whorls and a decrease in
      frequency of ulnar loops than the controls. Patients with bruxism demonstrated a
      lower frequency of atd angle than controls. Augmentation of I loops and t
      triradii and diminution of IV, H and t" triradii were observed in bruxism
      patients. Furthermore, the main line A ended more frequently in sector 5' in
      bruxism patients when compared with controls. There is no significant difference
      between the total finger ridge counts (TRC) and a-b ridge counts the subjects
      with bruxism and that of the controls. The dermatoglyphic patterns of finger and
      palm was significantly different in children with bruxism. When combined with
      other clinical features in bruxism, dermatoglyphics can serve to strengthen a
      diagnostic impression.

PMID- 11314142
TI  - A cephalometric study of the effect of extraction of lower first permanent
      molars.
AB  - The sample consisted of 28 patients (16 female: 12 male) from the records of the
      Orthodontic Department for whom the extraction of both lower first permanent
      molars was considered due to caries. The age ranged from 8-14 years (mean age
      12.4). A cephalometric radiograph was taken prior to the extraction and after a
      mean of 18 months. No other treatment was done during the observation period. The
      radiographs were traced arid digitized using the GeLa program. A total of 16
      points were digitized yielding 19 measurements (7 angular and 12 linear). The
      data were analyzed using 't' test and Pearson Correlation Coefficients in SPSS PC
      and compared to a control group matched for age and sex. Results showed that on
      average, the lower second molar moved forwards 5.9 mm. On average there was no
      change in angulation of the incisors to the bases. There was no significant
      change in the vertical relations of the jaws save that caused by normal growth
      and development. A significant correlation was found between the change in
      overbite and original overbite (r = -0.55, P < 0.01), the change in Li/A-Pog (r =
      0.41, P < 0.05) and the change in facial proportions (r = -0.59, P < 0.001). The
      change in overjet was correlated with the change in Li/A-Pog (r = 0.58, P <
      0.001) and change in Li/mand (r = -0.55, P < 0.01). The extraction of the lower
      first molars results in deepening of the overbite on average, but has no effect
      on the anterior facial height or any other vertical relationship. However, the
      increase in overbite is associated with lingual positioning of the lower incisor
      and the change in facial proportions. The change in overjet is related to lingual
      positioning and retroclination of the lower incisors.

PMID- 11314143
TI  - Clinical evaluation of electronic dental anesthesia for various procedures in
      pediatric dentistry.
AB  - Electronic dental anesthesia (EDA) is a newer technique for achieving regional
      anesthesia by the application of transcutaneous electrical nerve stimulation
      (TENS). The present study intended to be an initial investigation of the
      attitudes of dentists and patients towards a relatively newly introduced EDA
      system. The purpose of the study was to evaluate the effectiveness of EDA system,
      a unit of TENS, in the management of pain during treatment procedures such as
      minor extractions, restorations (tooth preparations), and pulp therapy, in
      children. Overall, forty children between the age groups of 5 to 12 years were
      selected for three different clinical procedures. The response of the patients as
      well as the opinion of both, the clinician and the patient regarding perception
      of pain and comfort on administration I effectiveness of electronic anesthesia
      were recorded and analyzed. Significantly favorable results to the use of EDA
      were obtained, which indicate that EDA, besides offering safety and psychological
      advantages, may also be a promising alternative to the conventional methods of
      local anesthesia.

PMID- 11314144
TI  - Effect of etching agent on dentinal adhesive interface in primary teeth.
AB  - The purpose of this study was to evaluate in vitro the effect of a phosphoric
      acid etchant containing benzalkonium chloride on the dentin/adhesive interface in
      primary teeth. The teeth had caries lesions involving enamel and dentin, and were
      stored in a 2% glutaraldehyde solution for 2-4 hours. The teeth were divided into
      five groups of five teeth each: Group 1: Etching for 15 seconds with a semigel
      32% phosphoric acid containing benzalkonium chloride; Group 2: Etching with 35%
      phosphoric acid for 15 seconds; Group 3: Treated with a 2% benzalkonium chloride
      in a alcoholic solution; Group 4: Conditioned with a 3% benzalkonium chloride in
      a alcoholic solution (control group); Group 5: The teeth were untreated (control
      group). The carious tissue was removed with a carbide bur in high-speed and
      copious air water spray. The overall dimensions and depths of the cavities were
      determined by the carious tissue removal. After the caries lesion was removed,
      the cavity was cleaned with an air-water spray and the dentin was treated
      according to the specific group. The teeth were then restored with Scotchbond
      Multi-Purpose Plus (3M, St. Paul, MN) and Z-100 resin-based composite (3M, St.
      Paul, MN) according to the manufacturer's instructions. After the teeth were
      restored they were stored in water for 24 hours at room temperature and the
      restorations polished. After storage the teeth were thermally challenged for 500
      cycles in temperatures of 50 C and 550 C and then stored in 100% humidity until
      the sectioning procedures. The teeth were cut into two sections along the
      longitudinal axis through the center of the teeth and passed the mesial-distal
      surfaces through the restoration by using a double-face diamond disc with water
      coolant. The specimens were ground with 320 up to 600 grit silicon carbide paper
      and polished with 6 mm and 1 mm diamond paste and 0.25 pm alumina solution. The
      specimens were etched with 10% citric acid for 1 minute and washed with deionized
      water. After that, they were deproteinized with 10% NaOCl for 5 seconds. The
      specimens were dried at room temperature sputter-coated with gold and observed
      with an SEM for assessment of the morphology of the bonded interface. The
      interface was observed to determine the presence/absence of hybrid layer
      formation, resin tags, and gaps. In the groups treated only with benzalkonium
      chloride solutions, spaces were observed in the resin/dentin interface. Similar
      findings were observed in the control group, which received no treatment on the
      dentin before primer application. In these groups neither resin tags or hybrid
      layer formation was observed. The presence of an amorphous layer, which was
      unremoved smear layer, was noted. The group treated with 35% phosphoric acid
      showed a hybrid layer formation (8.15 microns). This layer was linked intimately
      with the peritubular and intertubular dentin. Tags formation was observed towards
      the pulp under the hybrid layer. In these specimens the gaps were not observed
      between the dentin layer and bonding materials. The total removal of the smear
      layer was observed using 37% phosphoric acid with benzalkonium chloride. A hybrid
      layer (+/- 7.32 microns) and resin-tags attached to this layer were observed
      similar to the group in which the 35% phosphoric acid was used. The samples
      showed total removal of the smear layer and no gaps were observed in the
      dentin/adhesive interface.

PMID- 11314145
TI  - Effect of different prophylaxis methods on sealant adhesion.
AB  - The objective of this study was to evaluate the retention of a light-cured
      sealant using previously different prophylaxis methods and two different etching
      times, thirty and fifteen seconds. Eighty, third molars surgically extracted were
      sectioned into two halves (buccal and lingual). The teeth were divided into 8
      groups of 20 samples each, according to prophylaxis type: pumice powder,
      fluoridated paste, sodium bicarbonate spray, and control (no prophylaxis); and
      etching time: 30 and 15 seconds. Tensile bond strengths were studied using a
      universal Instron testing machine. A statistical test ANOVA was used. No
      statistical differences were found when comparing both etching times, but when
      prophylaxis methods were compared a statistically significant higher retention
      was found in the sodium bicarbonate and fluoridated paste groups.

PMID- 11314146
TI  - Fluoride-releasing sealant and caries-like enamel lesion formation in vitro.
AB  - OBJECTIVE: The aim of this laboratory study was to evaluate the effects of a
      fluoride-releasing pit and fissure sealant (FS) and a conventional non-fluoride
      containing pit and fissure sealant (CS) on caries-like lesion formation in
      enamel. DESIGN: Twelve extracted, macroscopically caries-free human molar teeth
      underwent fluoride-free prophylaxis and were sectioned into toothquarters. Cavity
      preparations were placed in buccal and lingual surfaces of the toothquarters,
      acid-etched and filled with sealant material (per the manufacturer's
      instructions) as follows: 1) mesiobuccal and mesiolingual quarters--FS (Fissurit
      F, VocoChemie); and 2) distobuccal and distolingual quarters--CS (Fissurit,
      VocoChemie). Prior to caries formation in an acidified gel, the toothquarters
      were thermocycled (500 cycles) in artificial saliva. Sections were taken
      following caries initiation (6 week gel exposure) and caries progression (9 week
      gel exposure), and examined by polarized light microscopy to determine mean
      primary surface lesion depth and presence or absence of wall lesions. RESULTS:
      Mean surface lesion depths were significantly different between FS and CS groups
      following caries initiation (FS = 119 microns; CS = 157 microns, p < 0.05, paired
      t-test) and progression (FS = 169 microns; CS = 221 microns, p < 0.05, paired t
      test). Wall lesions were reduced in FS (14% initiation; 25% progression) when
      compared with CS (19% initiation; 35% progression); however, this was not
      significantly different (p > 0.05, paired t-test). CONCLUSION: A pit and fissure
      sealant containing releasable fluoride provided a caries inhibiting effect with a
      significant reduction in lesion depth in the surface enamel adjacent to the
      fluoride-releasing sealant and a tendency toward reduction in the frequency of
      wall lesions. CLINICAL SIGNIFICANCE: Fluoride release by pit and fissure sealants
      may provide additional protection against caries formation in cuspal incline
      enamel and smooth surfaces adjacent to sealed pits and fissures, and act as a
      fluoride reservoir with long-term release of fluoride into the immediately
      adjacent oral environment.

PMID- 11314147
TI  - An in vitro study of microleakage of occlusal composite restorations polymerized
      by a conventional curing light and a PAC curing light.
AB  - With the increase in usage of bonded dentistry procedures, so comes the
      development of advanced technology to polymerize it. The purpose of this in vitro
      study was to evaluate the microleakage of sealants and resin restorations
      utilizing two different curing lights. The conventional Ortholux curing light
      (OCL) and the Plasma Arc Curing (PAC) light attached to the KCP air abrasion unit
      of American Dental Technologies were utilized to polymerize sealants and resin
      restorations on extracted third molars and premolars. Forty-eight caries-free
      teeth were divided into 4 groups of 12 specimens. Occlusal sealants were
      polymerized on groups 1 and 3. Class I composite resin restorations were
      polymerized on groups 2 and 4. The PAC light polymerized group 2 and the OCL was
      used for groups 3 and 4. Therefore a comparison between the two light sources'
      polymerization could be measured by evaluating the microleakage of the two sets
      of specimens. The PAC light polymerized the Z100 adhesive for 5 seconds and the
      OCL polymerized it for 10 seconds. The Z100 A-1 composite placed in two 1 mm
      increments was polymerized with the PAC light for 10 seconds and the OCL for 40
      seconds. The teeth were thermocycled 200 times between 5 degrees C and 55 degrees
      C. The teeth, coated with fingernail polish excluding the occlusal surface, were
      soaked in 5% methylene blue for 4 hours, removed, and rinsed with water. The
      teeth were invested in clear resin (Castin Craft) and sectioned longitudinally
      using an Isomet diamond saw. Microleakage was scored "0" if no leakage was
      present. Scored "1" if the leakage was present to 1/2 the preparation depth.
      Scored "2" if the leakage was present past the 1/2 way point but not to the
      pulpal floor of the preparation. A score of "3" was used if the leakage reached
      the pulpal floor. Unpaired t-Tests were used to statistically analyze the data. A
      significant difference (p < 0.05) was found between groups 1 and 3. The PAC light
      used to polymerize the sealants in group 1 produced no microleakage. A
      significant difference (p < .005) was found between groups 2 and 4. The OCL
      produced less microleakage (16 and 20 out of 24 sections) than the resin
      restorations polymerized with the PAC (only 8 of 24 sections with no
      microleakage. The 10-second cure by the PAC light appears to be insufficient in
      polymerizing a class I composite resin restoration. Possibly longer exposures
      with the PAC would produce less microleakage. Further research needs to be
      performed to evaluate if the PAC light, with an intensity of 1196 mW/cm2, may be
      producing high levels of strain within the setting composite. This strain may be
      responsible for the statistically significant increase in microleakage of the
      restorations polymerized with the PAC light.). It appears the PAC light would be
      best utilized to cure sealants and/or possibly polymerize orthodontic brackets.
      The conventional curing light appears to remain the best choice for polymerizing
      class I composite restorations.

PMID- 11314148
TI  - The correlation between occlusal characteristics and temporomandibular
      dysfunction in Saudi Arabian children.
AB  - The aim of the present study was to investigate the association between the
      different occlusal characteristics and signs and symptoms of temporomandibular
      dysfunction (TMD) in children with primary dentition in the western region of
      Saudi Arabia. A total of group of 502 children 4-6 years old residing in the city
      of Jeddah, Saudi Arabia provided the data for analysis. The result of this study
      showed significant correlation between signs and symptoms of TMD and some of the
      occlusal characteristics including posterior crossbite (P < 0.05), edge to edge
      (P < 0.013), anterior openbite (P < .036) and class III canine relationship and
      as well as asymmetrical canine relationship (P < .048 and P < .046 respectively).
      On the other hand, no correlation was reported between signs and symptoms of TMD
      and the remaining occlusal characteristics. The lack of significant correlation
      between TMD and some of the occlusal variants could be attributed to sampling and
      methodology differences. However, the present study supported the previous
      conclusion that temporomandibular dysfunction is multifactorial and highlights
      the importance of early intervention to prevent further consequences to the TMD
      and permanent occlusion.

PMID- 11314150
TI  - Peripheral giant cell granuloma: three case reports.
AB  - Three cases of peripheral giant cell granuloma (PGCG) with histopathological and
      long-term evaluations are presented. In all the cases that were all female and
      ages ranged between 5.5 to- 12 years, after complete surgical excision of the
      lesion no recurrence was detected during a follow-up period of 2 to 4 years.
      Although etiological factors could not be determined exactly, low socioeconomic
      status of the patients and unfavorable oral hygiene seemed to be the predisposing
      factors.

PMID- 11314149
TI  - Effects of three different infant dentifrices on biofilms and oral
      microorganisms.
AB  - The purpose of this work was to evaluate the effects of infant dentifrices: A-
      with lactoperoxidase, glucose oxidase and lactoferrin; B--with 1100 ppm of NaF
      and sodium lauryl sulfate; C--with extract of calendula. The dentifrices were
      test on biofilms formed in vitro from saliva and dental plaque of infants, using
      reference strains A. viscosus (ATCC 43146); C. albicans (ATCC 51501); L. casei
      (ATCC 4646); S. mitis (ATCC 49456); S. mutans (ATCC 25175); S. oralis (ATCC
      35037); S. sanguis (ATCC 10586); S. sobrinus (ATCC 27609) and isolated clinically
      microorganisms C. albicans, S. mitis, S. mutans, S. oralis, S. sanguis, S.
      sobrinus and Lactobacillus sp. Twenty infants were chosen, who were beginning
      treatment at the Infants Clinic of the Pediatric Dentistry Department, Federal
      University of Rio de Janeiro. A pool of unstimulated saliva and a pool of dental
      plaque were collected from which biofilms were produced. Supernatants from each
      dentifrice were prepared and concentrated and diluted solutions of the
      dentifrices and a control sterile diluent were tested against the biofilms
      produced, for 1 and 3 minutes, and against the microorganisms. The results were
      statistically analyzed by the ANOVA and Tukey Test. After the exposure of the
      biofilms produced both from saliva and from dental plaque, to the dentifrice B
      concentrated and 1/2, for 1 and 3 minutes, the viable microorganisms count
      (CFU/ml), compared to the controls, was significantly reduced (p < 0.05).
      However, exposure to the dentifrices A and C concentrated and dentifrice B 1/4
      and 1/8, for 1 and 3 minutes, was not significantly lethal to the biofilms. The
      dentifrices A and C, either concentrated or diluted (1/2 to 1/128) and the
      dentifrice B in the dilutions 1/16 to 1/128 did not have an antimicrobial effect
      on any microorganism evaluated. For all the microorganisms evaluated, the
      dentifrice B concentrated and in the 1/2 dilution showed a significant
      antimicrobial effect, when compared with the control (p < 0.05).

PMID- 11314151
TI  - Craniofacial characteristics of Klippel-Feil syndrome in an eight year old
      female.
AB  - A female eight year, one month old patient with Klippel-Feil syndrome has been
      introduced. General appearance of the patient was characterized by short neck
      with limited head movements, craniofacial asymmetry, low posterior hairline and a
      short stature. Cephalometric analysis revealed a Class I dentoskeletal pattern
      with an excessive mandibular plane angle and fused cervical vertebrae. Panoramic
      radiogram showed congenitally missing lower second premolars and right central
      incisor.

PMID- 11314152
TI  - Deciding for imperilled newborns: medical authority or parental autonomy?
AB  - The ethical issues around decision making on behalf of infants have been
      illuminated by two empirical research studies carried out in Scotland. In-depth
      interviews with 176 medical and nursing staff and with 108 parents of babies for
      whom there was discussion of treatment withholding/withdrawal, generated a wealth
      of data on both the decision making process and the management of cases. Both
      staff and parents believe that parents should be involved in treatment limitation
      decisions on behalf of their babies. However, whilst many doctors and nurses
      consider the ultimate responsibility too great for families to carry, the
      majority of parents wish to be the final arbiters. We offer explanations for the
      differences in perception found in the two groups. The results of these empirical
      studies provide both aids to ethical reflection and guidance for clinicians
      dealing with these vulnerable families. They demonstrate the value of empirical
      data in the philosophical debate.

PMID- 11314153
TI  - Is it in a neonate's best interest to enter a randomised controlled trial?
AB  - Clinicians are required to act in the best interest of neonates. However, it is
      not obvious that entry into a randomised controlled trial (RCT) is in a neonate's
      best interest because such trials often involve additional onerous procedures
      (such as intramuscular injections) in return for which the neonate receives
      unproven treatment or a placebo. On the other hand, neonatology needs to develop
      its evidence base, and RCTs are central to this task. The solution posited here
      is based on two points. First, "best interest" is not equivalent to "the best
      possible interest" only to "best interest within a certain realm". The realm of
      deliberation when asking the title question is the neonate's health. Deliberating
      in this realm may involve the exclusion from consideration of some factors that
      might be thought relevant (such as parental wealth). Furthermore, circumstances
      may dictate the need to deliberate on other factors that might be thought
      irrelevant (such as health care resources). Second, deciding on a neonate's best
      interest does not involve "putting oneself in its shoes". Rather, it involves
      asking in what it has an interest, or stake. These will include some things in
      which we all, as human beings, have a stake, such as medical progress. Putting
      these two points together, in the realm of health the answer to whether RCT entry
      is in a neonate's best interest is usually very finely balanced. Where this is
      the case, it is reasonable to invoke a broader notion of best interest and
      include a broader range of elements in which the neonate has a stake, including
      medical progress. In this way RCT entry can, usually, be said to be in a
      neonate's best interest.

PMID- 11314154
TI  - The value of taking an 'ethics history'.
AB  - OBJECTIVES: To study the value of taking an ethics history as a means of
      assessing patients' preferences for decision making and for their relatives'
      involvement. DESIGN: Questionnaire administered by six junior doctors to 56
      mentally competent patients, admitted into general and geriatric medical beds.
      SETTING: A large district general hospital in the United Kingdom. MAIN MEASURES:
      To establish whether patients were adequately informed about their illness and
      whether they minded the information being communicated to their relatives. To
      establish their preference regarding truthful disclosure and participation in
      decision making with risk attached. To establish whether they wished to be
      involved in CPR decision making, and if not, who should make the decision. To
      establish whether they knew of living wills and whether they had any advance
      directives. RESULTS: Twenty-four (43%) were inadequately informed of their
      illness. Forty-six (82%) said they would want to know were something serious to
      be found. Twenty-eight (50%) wanted to make their own decision if requiring risky
      treatment and 11 (20%) wanted family members involved. Thirty-one (55%) wanted to
      make a cardiopulmonary resuscitation (CPR) decision and five of these decisions
      differed from those made by the doctors. Twenty-five (45%) preferred the doctors
      to decide. Eleven (20%) of the patients had heard of living wills but only one
      had executed such a will. Seven (13%) of the patients wished to provide advance
      directives. Three (5%) did not find the history taking helpful but none were
      discomforted. CONCLUSION: Taking an ethics history is a simple means of obtaining
      useful information about patients' preferences.

PMID- 11314155
TI  - Assessing the ethical weight of cultural, religious and spiritual claims in the
      clinical context.
AB  - The aim of this paper is to expand upon the conclusions reached by Orr and
      Genesen in their 1997 article (published in this journal), Requests for
      'inappropriate' treatment based on religious beliefs. Assuming, with Orr and
      Genesen, that claims made in the name of religion are not absolute, I will
      propose some principles for determining when claims based on religious beliefs or
      cultural sensibilities "trump" other considerations and when they do not.

PMID- 11314156
TI  - Dealing with prejudice.
AB  - Few of us are free of all prejudices, however subtle and subconscious, and they
      may affect both patient care and teaching. Here I use reflection about a patient
      with HIV infection, from the points of view of two doctors caring for him and the
      patient himself, to explore prejudice against lifestyles that are considered
      "dangerous". The paper then goes on to discuss research about physicians'
      attitudes to such cases, the teaching of ethics in a clinical environment and the
      need to support junior medical staff.

PMID- 11314157
TI  - Extending the boundaries of the Declaration of Helsinki: a case study of an
      unethical experiment in a non-medical setting.
AB  - To examine the ethical issues involved in governmental decisions with potential
      health risks, we review the history of the decision to raise the interurban speed
      limit in Israel in light of its impact on road death and injury. In 1993, the
      Israeli Ministry of Transportation initiated an "experiment" to raise the
      interurban speed limit from 90 to 100 kph. The "experiment" did not include a
      protocol and did not specify cut-off points for early termination in the case of
      adverse results. After the raise in the speed limit, the death toll on interurban
      roads rose as a result of a sudden increase in speeds and case fatality rates.
      The committee's decision is a case study in unfettered human experimentation and
      public health risks when the setting is non-medical and lacks a defined ethical
      framework. The case study states the case for extending Helsinki type safeguards
      to experimentation in non-medical settings.

PMID- 11314158
TI  - Medicine, lies and deceptions.
AB  - This article offers a qualified defence of the view that there is a moral
      difference between telling lies to one's patients, and deceiving them without
      lying. However, I take issue with certain arguments offered by Jennifer Jackson
      in support of the same conclusion. In particular, I challenge her claim that to
      deny that there is such a moral difference makes sense only within a utilitarian
      framework, and I cast doubt on the aptness of some of her examples of non-lying
      deception. But I argue that lies have a greater tendency to damage trust than
      does non-lying deception, and suggest that since many doctors do believe there is
      a moral boundary between the two types of deception, encouraging them to violate
      that boundary may have adverse general effects on their moral sensibilities.

PMID- 11314159
TI  - Late lessons from Auschwitz--is there anything more to learn for the 21st
      century?

PMID- 11314160
TI  - Treatment of patients who are Jehovah's Witnesses.

PMID- 11314161
TI  - Jehovah's Witnesses--the blood transfusion taboo.

PMID- 11314162
TI  - After 20 years, some reflections and farewell!

PMID- 11314163
TI  - 'What is (mental) disease?': an open letter to Christopher Boorse.
AB  - This "open letter" to Christopher Boorse is a response to his influential
      naturalist (value-excluding) analysis of disease from the perspective of
      linguistic-analytic value theory. The key linguistic-analytic point against
      Boorse (and other naturalists) is that, although defining disease value free, he
      (and they) continue to use the term with clear evaluative connotations. A
      descriptivist (value-entailing) analysis of disease would allow value-free
      definition consistently with value-laden use: but descriptivism fails when
      applied to mental disorder because it depends on shared values whereas the values
      relevant to mental disorders are highly diverse. A part-function analysis,
      similarly, although initially persuasive for physical disorders, fails with the
      psychotic mental disorders because these, characteristically, involve
      disturbances of the rationality of the person as a whole. The difficulties
      encountered in applying naturalism to mental disorders point, linguistic
      analytically, to the possibility that there is, after all, an evaluative element
      of meaning, deeply hidden but still logically operative, in the concept of
      disease.

PMID- 11314164
TI  - Views of the person with dementia.
AB  - In this paper I consider, in connection with dementia, two views of the person.
      One view of the person is derived from Locke and Parfit. This tends to regard the
      person solely in terms of psychological states and his/her connections. The
      second view of the person is derived from a variety of thinkers. I have called it
      the situated-embodied-agent view of the person. This view, I suggest, more
      readily squares with the reality of clinical experience. It regards the person as
      embedded in a history and culture. The human person is also an embodied agent. I
      contend that this view encourages a more appropriate approach towards the ethical
      issues that arise in dementia and towards people with dementia.

PMID- 11314166
TI  - What makes a problem an ethical problem? An empirical perspective on the nature
      of ethical problems in general practice.
AB  - Whilst there has been considerable debate about the fit between moral theory and
      moral reasoning in everyday life, the way in which moral problems are defined has
      rarely been questioned. This paper presents a qualitative analysis of interviews
      conducted with 15 general practitioners (GPs) in South Australia to argue that
      the way in which the bioethics literature defines an ethical dilemma captures
      only some of the range of lay views about the nature of ethical problems. The
      bioethics literature has defined ethical dilemmas in terms of conflict and choice
      between values, beliefs and options for action. While some of the views of some
      of the GPs in this study about the nature of their ethical dilemmas certainly
      accorded with this definition, other explanations of the ethical nature of their
      problems revolved around the publicity associated with the issues they were
      discussing, concern about their relationships with patients, and anxiety about
      threats to their integrity and reputation. The variety of views about what makes
      a problem a moral problem indicates that the moral domain is perhaps wider and
      richer than mainstream bioethics would generally allow.

PMID- 11314167
TI  - Your health. The silent disease: osteoporosis.

PMID- 11314165
TI  - Advance directives in psychiatric care: a narrative approach.
AB  - Advance directives for psychiatric care are the subject of debate in a number of
      Western societies. By using psychiatric advance directives (or so-called "Ulysses
      contracts"), it would be possible for mentally ill persons who are competent and
      with their disease in remission, and who want timely intervention in case of
      future mental crisis, to give prior authorisation to treatment at a later time
      when they are incompetent, have become non-compliant, and are refusing care. Thus
      the devastating consequences of recurrent psychosis could be minimised. Ulysses
      contracts raise a number of ethical questions. In this article the central issues
      of concern and debate are discussed from a narrative perspective. Ulysses
      contracts are viewed as elements of an ongoing narrative in which patient and
      doctor try to make sense of and get a hold on the recurrent crises inherent in
      the patient's psychiatric condition.

PMID- 11314168
TI  - Internet dentist subject to board oversight.

PMID- 11314169
TI  - ODA sponsored medical insurance.

PMID- 11314171
TI  - Go to the head of the class?

PMID- 11314170
TI  - Oral pathology. Case of the quarter.

PMID- 11314172
TI  - Customized metal coping for elastic traction of an ectopic maxillary central
      incisor.

PMID- 11314173
TI  - Patients' perceptions before, during, and after orthodontic treatment.

PMID- 11314174
TI  - Lever-arm mechanics in lingual orthodontics.

PMID- 11314175
TI  - The K-9 spring for alignment of impacted canines.

PMID- 11314176
TI  - Transpalatal elastic for Class III surgical-orthodontic treatment.

PMID- 11314177
TI  - Orthodontic bonding: the next generation.

PMID- 11314178
TI  - The M and M's of aloe vera--is it for dentistry?

PMID- 11314179
TI  - Oral pathology case of the quarter.

PMID- 11314180
TI  - A simplified perspective for all-ceramic crown systems in the anterior region.

PMID- 11314181
TI  - Your health. Prostate cancer.

PMID- 11314182
TI  - Development of a device for the delivery of agents to bone during distraction
      osteogenesis.
AB  - Various agents have been theoretically and experimentally implicated as mediators
      of distraction osteogenesis (DO). The purpose of this study was to develop a
      vehicle for the potential delivery of these factors to the region of the
      distraction site in an attempt to manipulate this biologic process. Three adult
      mongrel dogs (12 months old) had oblique osteotomies performed bilaterally
      through the gonial regions. In group I, the external distracter was affixed to
      the right hemimandible of two dogs (n = 2 hemimandibles) with cannulated pins
      (external diameter = 1.5 mm; lumen diameter = 1.0 mm; length = 60 mm), whereas
      the distracter on the left was affixed with standard, noncannulated pins of the
      same dimensions. In group II, cannulated pins were used to affix the external
      distracter to both hemimandibles (n = 2 hemimandibles) of a dog. The devices were
      activated after a 5-day latency period and were lengthened at a rate of 1 mm/day
      for 20 days. During the distraction period, 0.1 ml/d of sterile india ink was
      injected into the cannulated pins, after which the sterile stylet was replaced.
      The activation protocol was followed by 28 days of fixation (consolidation
      period). The hemimandibles from group I underwent removal of soft tissues,
      acetone fixation, and gross examination/photography, whereas the hemimandibles
      from group II were prepared for histologic evaluation (whole mount, hematoxylin
      and eosin staining). All dogs survived to the end of the study and demonstrated
      successful DO without evidence of complications. Hemimandibles in group I
      displayed evidence of india ink on both the lingual and buccal cortex around the
      cannulated pin site, in the regenerate and on the neocortices of the distracted
      segment. Hemimandibles of group II showed histologic evidence of the india ink
      being deposited densely around the cannulated pin site and extending in a radial
      fashion around the pin site into the regenerate. This study demonstrates for the
      first time a vehicle device for the delivery of an inert dye to the regenerate
      site during distraction osteogenesis. This vehicle offers the potential of
      delivery of various factors implicated in distraction osteogenesis (i.e.,
      mitogens) in an attempt to alter this process and also substances (i.e.,
      chemotherapy, antibiotics, etc.) for use in the treatment of various
      osteopathies.

PMID- 11314183
TI  - Excellence in cleft lip and palate treatment.

PMID- 11314184
TI  - Imaging the neonatal mandible for accurate distraction osteogenesis.
AB  - The position of mandibular teeth is difficult to document in the neonatal
      patient. Panorex images are difficult to obtain in an uncooperative pediatric
      patient. The new technique presented by the authors uses computed tomographic
      data to create a curved, reformatted image of the mandible, and generates an
      image similar to a panorex image. This curved, reformatted mandibular image
      provides accurate visualization of the mandible and mandibular teeth. This
      technique allows for precise pin placement and osteotomy in distraction
      osteogenesis.

PMID- 11314185
TI  - Relationship in hypoplasia between the masticatory muscles and the craniofacial
      skeleton in hemifacial microsomia, as determined by 3-D CT imaging.
AB  - The purpose of this study, based on three-dimensional (3-D) computed tomographic
      (CT) reconstructions, was to evaluate the relation between underdevelopment of
      masticatory muscles and hypoplasia of the craniofacial skeleton in hemifacial
      microsomia (HFM). In 25 patients with HFM and 19 control patients the volumes of
      the masseter, the temporal, and the medial-pterygoid and lateral-pterygoid
      muscles were measured on the basis of CT scans, using three-dimensional
      segmentation and voxel addition. The size and shape of the craniofacial
      structures were classified, using three-dimensional imaging based on CT scans.
      Contiguous 1.5-mm computed tomography scans were made with a Philips Tomoscan 350
      and processed by a Cemax 1500X 3-D workstation. Using the Pearson product moment
      correlation coefficient, the Pruzansky/Kaban classification system, the new
      Craniofacial Deformity Scoring System, Cranial Deformity Scoring System, and
      Mandibular Deformity Scoring System (MDS) demonstrated correlation coefficients
      with the "masseter muscle percentage" varying from 0.71 to 0.81 (P < 0.05), with
      the medial pterygoid muscle percentage correlation coefficient varying from 0.43
      to 0.56 (P < 0.05), with the lateral pterygoid muscle percentage correlation
      coefficient varying from 0.55 to 0.61 (P < 0.05), and with the temporal muscle
      percentage correlation coefficient varying from 0.67 to 0.84 (P < 0.05). The
      normal right/left difference in volume of the masticatory muscles of the control
      patients, calculated as a percentage of the total, demonstrated small differences
      of 3.4% to 4.8%. Bony malformations are associated with underdevelopment of the
      masseter and the temporal muscles, and demonstrate a tendency toward a clear
      relationship. The degree of muscular underdevelopment of the different muscles of
      mastication in one patient could vary widely. The normal right/left difference of
      the masticatory muscles of the control patients is minimal. The volume of the
      masticatory muscles of the non-affected side does not demonstrate a compensatory
      effect in patients with HFM.

PMID- 11314186
TI  - Compartmentalized bone regeneration of cranial defects with biodegradable
      barriers: an animal model.
AB  - In bony defects of the cranium, bone healing may be complicated by prolapse of
      surrounding tissue into the defect. This tissue acts as an impediment to prevent
      the migration of osteogenic cells, leading to impaired bone formation. It has
      been previously shown that a membrane placed over the bony defect inhibits the
      connective tissue cells from entering the wound and theoretically improves bone
      formation. The use of a proven resorbable material, Lactosorb, is used in this
      animal model and has shown a significant increase in autogenous bony formation.
      The majority of previous work was accomplished with nonresorbable material that
      resulted in foreign body formation. This paper is unique because resorbable
      material in the animal model is relatively inexpensive and easy to use and has
      allowed successful autogenous bony regeneration.

PMID- 11314187
TI  - Le Fort I osteotomy with sparing fracture of lateral pterygoid plate.
AB  - This study aimed to clarify the relation between the anatomical variations of the
      pterygomaxillary region and fracture of the pterygoid plate during Le Fort I
      osteotomy. We present a secure method to separate maxillary tuberosities from
      pterygoid plates without injuring the pterygoid plates. Thirty specimens of
      hemisection of Korean skulls were used for the study. The maxilla was sectioned
      transversely on the floor of the pyriform aperture and posteriorly to the lateral
      pterygoid plate with a mechanical saw. The section was 5 to 6 mm above the tooth
      roots. The pterygomaxillary junction was separated with a curved osteotome in two
      steps: initially with light tapping of the shallow groove 2 to 3 mm anterior to
      the pterygomaxillary fissure at a half right angle and then changing the course
      of forceful tapping to more than 60 degrees. The maxillary tuberosity separated
      from the medial and lateral pterygoid plates during the procedure was grouped
      into the "disjunction group" (24 of 30, 80%) and the pterygoid plates fractured
      were grouped into the "fracture group" (6 of 30, 20%). The thickness of the
      pterygomaxillary region (T) was significantly greater in the disjunction group
      than in the fracture group (P = 0.034). The concavity of the pterygomaxillary
      fissure (C) was significantly deeper in the disjunction group than in the
      fracture group (P = 0.020). There was no significant difference of width of the
      pterygomaxillary fissure between the disjunction group and the fracture group (P
      = 0.169). The thin pterygomaxillary region and less concave pterygomaxillary
      fissure on the preoperative computed tomography scan draw precautionary attention
      to vulnerable pterygoid plates fractured in the procedure of Le Fort I osteotomy.

PMID- 11314188
TI  - Resorption kinetics of eggshell: an in vivo study.
AB  - Eggshell has been recently introduced as a bone substitute candidate in
      reconstructive surgery. The aim of this experimental study study was to determine
      its degradation rate in both a skeletal and extraskeletal site. In experiment 1,
      eggshell particles with four different sizes (50, 75, 150, and 300 microns in
      diameter) were implanted in subcutaneous pouches of 30 rats. In experiment 2, a
      fragment of ostrich eggshell was implanted on the nasal dorsum of 10 rats.
      Animals were sacrificed at 1 (N = 10), 2 (N = 10), and 4 months (N = 10) during
      the first stage of the study, and at 1 year during the second stage of the study.
      The results were assessed by X-ray examination and routine histological
      techniques. In experiment 1, all animals healed uneventfully. At 1 month, only 50
      micron particles had undergone resorption. At 2 months, both 50- and 75-micron
      particles had undergone resorption. At 4 months, the 150- and 300-micron
      particles were resorbed incompletely. Histologically, the eggshell elicited a
      mild inflammatory reaction at 1 month that decreased progressively at further
      stages. In experiment 2, all animals except one healed uneventfully.
      Radiologically, the eggshell implant displayed a noticeable stability.
      Histologically, seven of nine implants were encapsulated, but two of them were
      surrounded by a bony rim. In conclusion, eggshell is a resorbable implant, but
      the degradation kinetic is size dependent. Large ostrich grafts are also suitable
      as onlay graft, but a complementary osteosynthesis is recommended to enhance
      osteointegration.

PMID- 11314189
TI  - Intraindividual comparative animal study of alpha- and beta-tricalcium phosphate
      degradation in conjunction with simultaneous insertion of dental implants.
AB  - An intraindividual comparative study of proximal tibial marrow defects in nine
      adult Goettinger miniature pigs (GMPs) was undertaken. The left side of the
      defect was filled with granular beta-tricalcium phosphate (TCP) ceramic ad modum
      Cerasorb, and the right side was filled with granular alpha-TCP ceramic ad modum
      Biobase alpha pore. Simultaneously, dental screw implants were inserted in each
      ceramic and fixed within the orthotopically replanted corticalis lids. Control
      defects were made in two other animals. The survival period ranged from 4 to 86
      weeks (control study, 16 and 20 weeks). The reorganization and degree of bone
      regeneration, dynamics of ceramic degradation, and remodeling characteristics of
      the bone regenerate referring to osseo-integration of the dental implants were
      examined histomorphologically in nondecalcified specimens. The results reveal
      that both ceramic types were osteoconductive exclusively. Centripetally oriented
      angiogene bone regeneration occurred at the margins of the circular defects.
      Ceramic degradation was performed hydrolytically and within cells. Furthermore,
      it was demonstrated that decomposition of the intratrabecularly integrated
      ceramic residues underlies a dynamic process of degradation. Within 86 weeks,
      nearly 80% to 90% of the larger alpha-TCP granules, and nearly 90% to 95% of the
      beta-TCP granules were degraded. At this time, especially for the alpha-TCP
      modification, ceramic microparticles were found in the marrow, either unbound or
      within polynuclear macrophages. The predictable degradation of both ceramic types
      provides an early functional adaptation of bone regenerates and facilitates a
      biofunctional, anisotropic orientation of the neotrabeculae without delay. It is
      concluded that because of the initially pronounced accumulation of macrophages,
      dental implants should not be inserted simultaneously with ceramic, but after
      further progress of ceramic degradation (5 to 6 months after TCP implantation).

PMID- 11314190
TI  - Frontoethmoidal encephaloceles: reconstruction and refinements.
AB  - Frontoethmoidal encephaloceles are herniations of the intracranial contents
      through a defect in the skull at the junction of the frontal and ethmoidal bones.
      They are generally classified as nasofrontal, nasoethmoidal, and naso-orbital,
      although there may be some overlap or multiplicity. The records of 35 patients
      treated for frontoethmoidal encephaloceles were examined. Of these, 12 cases with
      complete and accurate medical records were evaluated in detail. The successful
      correction of frontoethmoidal encephaloceles was shown to depend on the
      following: a detailed understanding of the pathological anatomy (such as
      interorbital hypertelorism rather than true orbital hypertelorism and the
      presence of secondary trigonocephaly), careful planning of the bone movements to
      correct these deformities, and attention to detail regarding the placement of
      scars, positioning of the medial canthi, and the nasal reconstruction. Avoiding
      the "long-nose" deformity often seen after repair should be a priority. In
      general, the authors recommend a one-stage repair with both a transcranial and
      external approach.

PMID- 11314191
TI  - Functional impact of distraction osteogenesis of the midface on expressive
      language development.
AB  - This is a discussion of the impact of distraction osteogenesis on the major
      function of communication as noted in oral motor control for expressive language.
      Our experience has been primarily with preadolescent and adolescent patients of
      school age whose expressive language skills are undergoing continuing
      development.

PMID- 11314192
TI  - A case of improved obstructive sleep apnea by distraction osteogenesis for
      midface hypoplasia of an infantile Crouzon's syndrome.
AB  - We performed Le Fort III midfacial advancement with gradual distraction using
      internal devices on a 2-year 5-month-old boy with Crouzon's syndrome with
      associated severe obstructive sleep apnea. The device was not activated until 7
      days after surgery, after which the distraction was initiated, 1 mm per day, and
      the midface was advanced 4 mm intraoperatively and distracted 12 mm
      postoperatively. A total advancement of 16 mm was obtained. The obstructive sleep
      apnea improved remarkably after the distraction. In infants and younger children
      with associated severe obstructive sleep apnea, advancement by distraction
      osteogenesis of the midface in Le Fort III maxillary osteotomy will be initially
      indicated to obviate tracheostomy improving the upper airway obstruction.

PMID- 11314193
TI  - Abrikossoff's tumor.
AB  - Abrikossoff's tumor is a disease that more commonly affects the oral cavity but
      can also occur at other sites. It develops between the second and sixth decades
      of life, more frequently among women and blacks. The neoplasm can affect all
      parts of the body. The head and neck areas are affected in 45% to 65% of cases
      and of these, 70% are located interorally (tongue, oral mucosa, hard palate). The
      benign form shows polygonal cells with granular, eosinophilic cytoplasm and small
      nuclei. The malignant form, however, is associated with a high mitotic index and
      pleomorphic cellular tissue. The clinical aspect of the neoformation is a
      swelling covered by mucus of normal appearance. Studies of the neoformation show
      that in addition to the objective examination, further instrumental research is
      necessary, i.e., with nuclear magnetic resonance or computed tomography with
      contrast CT scan. However, the only examination that can confirm the clinical
      diagnosis is the histological examination. The only treatment for Abrikossoff
      tumor is surgery. The surgical treatment provides for an extirpation of the
      neoformation with the overhanging mucus and the underlying periosteum. In this
      work, the authors discuss a case of Abrikossoff tumor affecting the mucus of the
      right side of the hemipalate in a 53-year-old patient and present a review of the
      literature.

PMID- 11314194
TI  - Retained foreign body in the orbit and cavernous sinus with delayed presentation
      of superior orbital fissure syndrome: case report.
AB  - Reports of delayed onset of neurological symptoms after penetrating intracranial
      trauma are rare. We present the case of a patient who presented with superior
      orbital fissure syndrome 72 hours after reported trauma to the right eye.
      Subsequent workup revealed a foreign body located within the orbit, passing
      through the superior orbital fissure and into cavernous sinus, impinging on the
      right cavernous carotid artery. Evidence of an intraorbital abscess was also
      present. Surgical management consisted of a combination of frontopterional and
      orbital approaches to fully expose both the cavernous sinus and the orbital
      contents. The foreign body was removed and the abscess was drained. The carotid
      artery was found to be intact. At 10-month follow-up examination, a slight ptosis
      and medial gaze of the right eye persist. All other symptoms have resolved.

PMID- 11314195
TI  - CT-based size and shape determination of the craniofacial skeleton: a new scoring
      system to assess bony deformities in hemifacial microsomia.
AB  - The purpose of this study was to design a better craniofacial classification
      system for bony deformities in patients with hemifacial microsomia than the
      existing ones. It was meant to incorporate the deformity of the craniofacial
      skeleton other than that of the mandible. The "Mandibular Deformity Scoring"
      System (MDS), the "Cranial Deformity Scoring" System (CDS), the the "Craniofacial
      Deformity Scoring" System (CFDS) are three newly developed classification
      systems, which are based on three-dimensional computed tomography (3-D CT)
      reconstructions. The size and shape of the craniofacial structures of 34
      children, 25 with hemifacial microsomia and 9 with minimal dysplasia or trauma,
      were determined from CT scans, using 3-D image segmentation and rendering.
      Contiguous 1.5-mm CT scans were made using a Philips Tomoscan 350 and were
      processed using a Cemax 1500X 3-D workstation. The precision of the 3-D imaging
      was assessed by repeated determinations carried out by two observers (intra- and
      interreliability). Accuracy of the bone determination technique was assessed by
      comparing the interpretations of the craniofacial skeleton by 3-D CT
      reconstructions of laser-stereolithographic 3-D models. Correlations of the
      Pruzansky/Kaban classification system and the newly developed classification
      systems were demonstrated by the use of the Pearson product moment correlation
      coefficients. The new CFDS (= CDS + MDS) provides an adequate basis for
      assessment of bony structures using three-dimensional imaging and demonstrates a
      high correlation with the known Pruzansky/Kaban classification system. This new
      scoring system can handle the wide variety of individual variation of the
      deformity seen in patients with hemifacial microsomia better than the existing
      scoring systems.

PMID- 11314196
TI  - Re: Periodontal evaluation in patients undergoing maxillary expansion.

PMID- 11314197
TI  - Re: Producing a full-scale model from computed tomographic data with the rapid
      prototyping technique using the binder jet method: A comparison with the laser
      lithography method using a dry skull.

PMID- 11314198
TI  - Re: Helmet versus nonhelmet treatment in nonsynostotic positional posterior
      plagiocephaly.

PMID- 11314199
TI  - Paul Tessier, creator of a new surgical specialty, is recipient of Jacobson
      Innovation Award.

PMID- 11314200
TI  - Reduction of maxillary intermolar width in Class III surgical-orthodontic
      treatment.

PMID- 11314201
TI  - A precise and predictable laboratory procedure for indirect bonding.

PMID- 11314202
TI  - A quick and simple method of reactivating space-opening push-coil springs.

PMID- 11314203
TI  - Orthodontic management of an impacted maxillary canine with an abnormal premolar
      root.

PMID- 11314204
TI  - Implementing the patient manager system.

PMID- 11314205
TI  - Creating your next office.

PMID- 11314206
TI  - Oral manifestations of HIV positive children.
AB  - Oral manifestations in HIV positive children were observed in thirty-eight HIV
      infected children that have received care at the Special Care Dentistry Center
      (SCDC) of the School of Dentistry, University of Sao Paulo. Results have shown
      that 52.63% of the children presented at least one oral manifestation related
      with HIV/AIDS. Angular cheilitis occurred in 28.94%, parotid gland bilateral
      enlargement, pseudomembranous candidiasis and erythematous candidiasis in 18.42%,
      conventional gingivitis in 13.15%, herpes simplex in 5.26%, hairy leukoplakia,
      recurrent aphthous ulcer and condyloma acuminatum in 2.63%. Although enamel
      hypoplasia occurred in 23.68%, this could not be attributed specifically to HIV
      infection.

PMID- 11314207
TI  - Oral manifestations of infections of infections due to varicella zoster virus in
      otherwise healthy children.
AB  - Varicella zoster virus (VZV) causes varicella (or chickenpox) and establishes
      latency in nerve ganglia after the primary infection. The reactivation of virus
      later in life can cause mono- or polyneuropathy. The cranial nerves most commonly
      involved are five (herpes zoster or shingles), six, seven eight, nine and ten. In
      the present study we describe the oral lesions associated with VZV infections in
      normal children. In a 3 year period we examined 62 children, age 2 to 13 years
      old with diagnosed varicella and a 4 year old boy with herpes zoster at the 3rd
      branch of the trigeminal nerve. According to the clinical picture of varicella,
      the disease was defined as: (1) group A mild cases; (2) group B moderate cases;
      (3) group C severe. The manifestations of varicella were: mild varicella 19
      children, moderate 26 children and severe 17 children. The results of the present
      study indicate that the prevalence of oral manifestations of varicella is related
      to the severity of the disease. In 17 severe cases, oral lesions were always
      present and the number was between 5 to 30. From 26 moderate cases, oral lesions
      were observed in 23 and the number was between 2 to 10. From 19 mild cases, oral
      lesions were present only in 6 cases and their number was 1 or 2. Often
      varicella's oral lesions resemble manifestations of other entities, and this may
      cause differential diagnostics problems.

PMID- 11314208
TI  - Dentoalveolar response after protraction mask and expansion in males and females
      in the mixed dentition.
AB  - The purpose of this study was to determine the dentoalveolar response of class
      III patients in the mixed and late mixed dentition phases fitted with a
      protraction mask and expansion. The before and after cephalometric records of 74
      patients divided by sex were analyzed at ages 6 to 9 and 9 to 12 years to assess
      the dentoalveolar changes. Data was correlated by means of paired t tests and
      Scheffe's multiple contrasts. No significant changes were seen in all
      dentoalveolar relationships between the ages of 6 to 9 years and 9 to 12 years
      and between males and females. Maxillary teeth tended to be proclined, while
      mandibular teeth to become retroclined.

PMID- 11314210
TI  - External resorption associated with tooth eruption.
AB  - A case is presented with severe resorption on the mesial root of the mandibular
      first permanent molar in a patient with Juvenile Periodontitis. The follicle of
      the bicuspid is seen in contact with mesial root of the molar.

PMID- 11314209
TI  - Orthodontic correction of an ectopic mandibular first permanent molar: a case
      report.
AB  - Ectopic eruption of mandibular first molar is a rare clinical problem. It is one
      result of an improper balance in the forces of growth and eruption. A case of
      ectopic eruption of the mandibular first permanent molar is described and the
      technique for repositioning it is showed.

PMID- 11314211
TI  - Two cases of totally submerging buried primary molars: characterization of
      clinical behavior and discussion of cause.
AB  - Submerging buried tooth is a rare condition whose clinical characteristics are
      unclear. Two cases are reported of submerging buried maxillary second deciduous
      molar. A review of the literature in Japanese and English provides the clinical
      condition of the lesion and allows for discussion of its causes.

PMID- 11314212
TI  - Clinical evaluation of the efficacy of anesthesia and patient preference using
      the needle-less jet syringe in pediatric dental practice.
AB  - Most dentists are aware that local anesthetic injections produce the highest
      incidence of disruptive behavior in children. Both psychological and
      physiological monitoring of the response of children to dental injection, support
      empirical observations of clinicians. The needle-free injector delivers local
      anesthesia without the use of a needle. This is accomplished by delivering the
      anesthetic solution under high compressive forces. One hundred children between
      the ages of 3 to 13 years underwent operative procedures using Madajet XL. There
      was a statistically significant difference in favor of the instrument. The
      instrument was completely successful in providing anesthesia.

PMID- 11314213
TI  - Effect of antimicrobial agents on the micromorphology of primary dentin.
AB  - The use of disinfectants on the dentin surface contributes to superficial
      cleaning and removal of remaining microorganisms of the carious process. However,
      the effect of these agents on the adhesion of resin materials to the dentin
      surface of primary teeth has not been established. This study evaluated the
      dentin micromorphological effects due to the use of antimicrobial agents in the
      different depths of dentin. Twenty-five buccal surfaces of primary molars were
      prepared from the sectioned teeth, ground flat and polished with silicon carbide
      paper of different grits. The surfaces were treated with 32% phosphoric acid with
      benzalkonium chloride (Bisco), 35% phosphoric acid gel (3 M), 3% benzalkonium
      chloride solution by itself or 10% maleic acid. All agents were applied for 15
      seconds on the dentin surface. The samples were washed with distilled water,
      dried and coated with gold for observation of the dentin surface with the
      scanning electron microscope. The samples were subdivided according to the dentin
      depth in upper, middle and lower areas. The following was observed: presence of
      smear layer, opening of the dentin tubules, and inter and intratubular dentin
      morphology. The effects of the antimicrobial agents were compared in the
      different depths of the dentin. The results demonstrated that the surface
      conditioned with 3% benzalkonium chloride solution presented few disclosed dentin
      tubules. The use of the 32% phosphoric acid with benzalkonium chloride completely
      removed the smear layer and increased the diameter of the dentin tubule openings.
      The 35% phosphoric acid totally exposed the tubules in the upper area of the
      analyzed surface but partially exposed them in the middle and lower areas. The
      10% maleic acid totally removed the smear layer, left all the tubules opened and
      conditioned the intertubular dentin. It was concluded that in the different
      depths of the dentin surface, conditioning with 10% maleic acid in primary teeth
      showed the most consistent micromorphological characteristics compared to the
      other agents used in this study.

PMID- 11314214
TI  - Barcoll hardness of dental materials treated with an APF foam.
AB  - The hardness of a dental material is generally related to its mechanical
      properties. The purpose of this study was to evaluate the hardness of several
      resins and cements exposed to an APF Foam (Minute Foam, Oral-B). Four molds 6 x 2
      mm were prepared for each experimental condition with each of the following
      materials: Filtek P 60 (3 M); Silux Plus (3 M); Ariston pHc (Vivadent); F 2000 (3
      M); Vitremer Restorative (3 M) and lonofil Molar (Voco). Immediately after
      prepared, the samples were stored in water or in the APF foam. To evaluate the
      Barcoll hardness, measurements were made on both sides of the specimens (top--T
      and bottom--B), immediately, and after 1 min, 24 h and 7 d. The results,
      expressed as percentages of the loss of hardness of each sample from the baseline
      readings, were analyzed with an ANOVA and Tukey's test. ANOVA revealed the
      significant influence of material, time and treatment. The surface analyzed (T or
      B) had no significance. Among the glass-ionomers tested the loss of hardness was
      significantly higher (+30%) than for resin-based composites (+/- 15%). Treatment
      with the APF foam for 7 days produced the greatest loss of hardness (42%) and at
      24 h the least (less than 5%). There were no other significant findings. It can
      be concluded that the effect of the APF foam is material dependent, but is
      significantly more pronounced with the glass-ionomers than the resins tested. The
      application time of the foam is the main factor for the loss of hardness.

PMID- 11314215
TI  - Mandibular deviations in TMD and non-TMD groups related to eye dominance and head
      posture.
AB  - This study was designed to determine whether eye-dominance affects head posture
      (rotation) and in turn, whether head posture is associated with mandibular frenum
      midline deviation, in both TMJ and control subjects. Eye dominance was determined
      using three tests: Porta, Hole, Point tests. Natural head posture was evaluated
      using the Arthrodial protractor. Mandibular frenum deviation was recorded as
      left, right or no deviation. Fifty female subjects were included in the study, 25
      TMJ patients attending the Gelb Craniomandibular Pain Center and 25 non-TMJ
      control subjects. The findings indicate that eye dominance and direction of head
      rotation are strongly associated in both TMJ and control subjects. Further, in
      TMJ subjects mandibular deviation occurred in greater frequency than in controls
      and tends to occur in the contra lateral direction of head rotation.

PMID- 11314216
TI  - Leiomyomatous hamartoma of the incisive papilla.
AB  - A case of unusual hamartoma in a six-year-old otherwise healthy Brazilian girl is
      reported, with emphasis on histological and immunohistochemical features. A mass
      observed in the incisive papilla was detected whose appearance was similar to
      congenital epulis or fibroma. Histological findings showed interlacing fascicles
      of large spindle cells resembling smooth muscle cells. Immunohistochemical
      staining for desmin and for smooth-muscle actin was positive. The histological
      diagnosis was leiomyomatous hamartoma, based on clinical and microscopic
      observations.

PMID- 11314217
TI  - Clinical features of incontinentia pigmenti with emphasis on dermatoglyphic
      findings.
AB  - Incontinentia pigmenti is a syndrome characterized by both systemic and oral
      manifestations. Presented here are the dental, clinical, radiological, genetic
      and dermatoglyphic findings of a 6 year old female case and her family members.
      The following features were apparent: oligodontia in maxillary and mandibular
      arches in both dentition, peg-shaped incisors and brown lesions on the body
      surface. No other problems were observed. The case had remarkable dermatoglyphic
      findings such as hypothenar loops associated with distally displaced axial
      triradii on both palms, reduced total finger and summed palmar a-b ridge-counts,
      decreasing plantar pattern intensity on the left sole. The other family members
      had similar dermatoglyphic characteristics. The paternal grand father, the father
      and the brother had eye defects.

PMID- 11314218
TI  - A rare non-syndrome case of concomitant multiple supernumerary teeth and partial
      anodontia.
AB  - Concomitant hypo-hyperdontia is an uncommon condition of coexistence of partial
      anodontia and supernumerary teeth. Its etiology is still unknown. Very few cases
      have been reported in the literature of this condition. Presented here is a rare
      and first such case of simultaneous presence of multiple supernumerary teeth and
      a missing tooth (canine) without any associated systemic conditions or syndromes
      involving both jaws.

PMID- 11314219
TI  - Congenital insensitivity to pain: report of two cases.
AB  - Congenital indifference or insensitivity to pain (CIP) is a rare syndrome. It
      mimics a number of other syndromes categorized under peripheral sensory
      neuropathies, often making early diagnosis difficult. Two cases from the middle
      east are presented, highlighting possible diagnostic, and management
      difficulties.

PMID- 11314220
TI  - Morphological characteristics of the deciduous teeth.
AB  - The morphology of the deciduous teeth was investigated. The mean mesiodistal
      crown dimensions of the deciduous canine, first and second molars and the mean
      buccolingual crown dimensions of the deciduous second molars in both dental
      arches of boys were significantly larger than that of girls. The upper deciduous
      first molar of girls was slender buccolingually and the lower deciduous second
      molar of boys was slender mesiodistally.

PMID- 11314221
TI  - Outcomes associated with supportive periodontal therapy in smokers and
      nonsmokers.
AB  - PURPOSE: This study evaluated the effects of smoking status on retrospective
      clinical and radiographic measures of periodontal disease and compared these to
      prospective changes in digital radiographic bone height. METHODS: Clinical data
      on moderate (4 to 6 mm) and severe (> 6 mm) periodontal pocket depths, and
      bleeding on probing, were obtained from 95 subjects on suggested three-month
      supportive periodontal therapy (SPT) for AAP Class III/IV periodontitis.
      Standardized radiographic data were obtained concerning posterior interproximal
      alveolar bone height from 36 of the 95 subjects using computer-assisted digital
      technology at baseline and one year later. The subjects were divided into groups
      by smoking status: current, former, and never. Data were evaluated using a
      general linear statistical model. RESULTS: Evaluation of clinical data showed
      that current smokers exhibited a significantly higher percentage of moderate
      (18%) and severe (1%) periodontal pockets than nonsmokers (10% and 0%,
      respectively; p < 0.002). Baseline radiographic interproximal bone height loss
      also was greater in current smokers (5.75 +/- 1.07 v. 4.64 +/- 1.16 mm). Bone
      loss over one year occurred in 5% of the sites, but was not significantly
      different among groups. CONCLUSION: Clinical periodontal pockets and bone loss
      accumulated more rapidly in smokers, even though they submitted to regular
      supportive periodontal therapy. Although this population was clinically compliant
      over a one year period, digital radiography showed a high incidence of detectable
      bone loss. The impact of smoking, however, may require longer than one year to
      show longitudinal changes. It is recommended that a periodic radiographic
      analysis on bone height be considered during SPT, and longer term studies be
      conducted in order to accurately identify the outcome of smoking status on this
      variable.

PMID- 11314222
TI  - Effect of topical fluoride on retention of pit and fissure sealants.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical effect of topical
      fluoride on retention of light-cured (CLC) and self-cured (CSC) pit and fissure
      sealants. METHODS: CLC and CSC sealants were placed in vivo on opposite sides of
      the arch before and after fluoride treatment. A total of 122 sealants were placed
      on virgin permanent molars and premolars of 16 dental hygiene students enrolled
      in a two-year program. Sealant retention in both fluoridated and non-fluoridated
      teeth was evaluated at 6, 12, and 18 month intervals. RESULTS: Overall sealant
      retention for both fluoridated and non-fluoridated teeth at 6, 12 and 18 months
      was 68%, 48%, and 49%, respectively. There was a significant difference (p <
      0.001) when fluoridated vs. non-fluoridated teeth were compared. Retention was
      greater on the fluoridated teeth, with respect to the sealant material (CLC
      fluoride). Significant differences (p < 0.001) were found when CLC-fluoride and
      CLC-no fluoride treatment groups were compared. However, no significant
      differences were found in retention when CSC-fluoride and CSC-no fluoride groups
      were compared, or when CLC was compared to CSC irrespective of fluoridation.
      Significant differences (p < 0.0001) were found when sealant retention on molars
      was compared to premolars--retention of sealants was greater on premolars.
      CONCLUSION: This study suggests that sealant retention may not be adversely
      affected by a topical fluoride treatment applied immediately prior to placement.

PMID- 11314223
TI  - Maryland dental hygienists' assessment of patients' risk behaviors for oral
      cancer.
AB  - PURPOSE: This study examined Maryland dental hygienists' knowledge of tobacco and
      alcohol use as oral cancer risk behaviors; the practice of obtaining
      comprehensive medical histories regarding patients' current, past, and
      type/amount of alcohol and tobacco used; and their opinions about the adequacy of
      their tobacco and alcohol cessation educational preparation in a state that ranks
      unusually high for oral cancer mortality rates. METHODS: The data source was the
      Maryland Oral Cancer Survey of Dental Hygienists conducted in November 1997
      (MDOCSDH, 1997) with a simple random sample of 700 dental hygienists selected
      from a registry of 2,677 licensed dental hygienists in Maryland. Data were
      collected with a 40-item self-administered mailed questionnaire. Unweighted data
      from 331 returned surveys (response rate = 60%) were analyzed using SAS and
      SUDAAN Software. Stratified and logistic data analysis techniques were utilized,
      and the results were evaluated statistically using a .05 level of significance.
      RESULTS: Nearly all of the responding dental hygienists knew that tobacco is an
      oral cancer risk factor. Most probed their patients' present use of tobacco in
      medical histories; however, fewer assessed patients' past use and type/amount of
      tobacco used. Very few believed that they were adequately prepared to provide
      tobacco cessation education, although the majority agreed that dental hygienists
      should be prepared to provide this type of information. The majority of
      respondents also knew that alcohol use is an oral cancer risk factor; however,
      less probed their patients' present use of alcohol in medical histories compared
      to assessing present tobacco use. Even fewer assessed patients' past use and
      type/amount of alcohol used. A very small minority believed that they were
      adequately prepared to provide alcohol cessation education. Yet, in contrast to
      tobacco cessation counseling preparation, few respondents believed that dental
      hygienists should be prepared to provide alcohol cessation education. There was a
      significant relationship (p < .05) between screening for all three aspects of
      tobacco use and agreement of dental hygienists that they were adequately prepared
      to provide tobacco cessation education. Of seven background characteristics,
      practice setting was the only one found to be positively associated (p < .05)
      with even one of three complete medical history screening indices--the practice
      of assessing all three tobacco screening items. CONCLUSION: There is a need to
      provide more complete and accurate information in tobacco and alcohol educational
      programs for Maryland dental hygienists. Additional research is needed to explore
      sources of noninterest or discomfort in assessing patients' use of these
      substances, since a substantial number of Maryland dental hygienists do not
      assess all aspects of patients' tobacco and alcohol usage and do not agree that
      dental hygienists should be prepared to provide tobacco and alcohol cessation
      education for their patients. Maryland dental hygienists' opinions regarding the
      adequacy of their tobacco and alcohol cessation education appear to accurately
      reflect their practice of obtaining comprehensive medical histories regarding
      these substances.

PMID- 11314224
TI  - Using the Internet to access oral health information.
AB  - The Internet is increasingly being used to access information, but it can be
      intimating and frustrating. Understanding the basics of the Internet and the
      World Wide Web, including how to evaluate the quality and accuracy of online
      resources, is essential for today's oral health educator and practitioner. This
      article provides the reader with Internet basics and five criteria to use when
      evaluating online information sources: authority, accuracy, objectivity,
      currency, coverage, and intended audience.

PMID- 11314225
TI  - Finding new solutions to old problems.

PMID- 11314226
TI  - Online continuing education for dental hygienists: DH forum.
AB  - There is a concern that excellent continuing education is difficult for many
      employed dental hygienists to obtain at locations distant from major metropolitan
      centers. This difficulty can change the practice mechanisms of these dental
      hygienists, and possibly affect patient care. The Dental Hygiene Program at
      Marquette University, Milwaukee, Wisconsin, began an innovative online program,
      "DH Forum," to address this concern. The program follows a case-based educational
      method of integration of theory into practice, so that learning is easily adapted
      to practice situations. The program also includes the latest in dental theory and
      practice, and links to many other informative Internet sites. Objectives of the
      online program were to meet the continuing education needs of dental hygienists
      in areas distant to metropolitan areas and pursue a high level of excellence in
      the areas of organization, material presented, appropriateness of material, and
      satisfaction of individual course objectives. An online feedback form using a
      simple survey method was used to obtain results. More than 86% of the initial 71
      participants who filled out the form are employed as dental hygienists in a
      variety of settings. More than 86% of these participants reside in areas distant
      from major metropolitan centers. In addition, more than 77% of these participants
      felt that overall, the program met its objectives on an excellent to near
      excellent level. Within its initial months of operation, the online feedback
      shows that the program has more than succeeded in meetings its objectives. Online
      continuing education for dental hygienists is a worthwhile addition to onsite
      continuing education programs for the advancement of high standards of care for
      all concerned, as long as certain considerations are followed. Further methods to
      evaluate online programs should be considered in the future.

PMID- 11314227
TI  - Evidence-based decision making in dental hygiene education, practice, and
      research.
AB  - PURPOSE: The purpose of this article is to highlight key aspects of the white
      paper prepared in 1999 for the American Dental Hygienists' Association (ADHA)
      Institute for Oral Health on Evidence-Based Decision Making and its Application
      to Dental Hygiene Education, Practice, and Research. These aspects include the
      need for evidence-based decision making, how it supports contemporary practice
      and education, basic evidence-based concepts, and strategies for integrating
      evidence-based decision making into dental hygiene. METHODS: A review of the
      biomedical literature, evidence-based Internet sites and textbooks, and clinical
      guideline development was systematically conducted to identify models of evidence
      based practice, skills needed to practice and teach evidence-based decision
      making (EBDM), and challenges faced by those implementing an EBDM approach. These
      resources were then analyzed and synthesized to develop a model for initiating
      the development of evidence-based dental hygiene practice. RESULTS: The need for
      using an evidence-based decision making approach was well supported throughout
      the literature. Consistency was found in how EBDM methodology and levels of
      evidence were defined and in the skills required for evidence-based practice.
      Implied in the use of an evidence-based approach were corresponding requirements
      in three areas: 1) redesigning educational programs to better prepare students
      and current practitioners to integrate the most current knowledge into their
      clinical decision-making; 2) conducting research for areas in which evidence
      applicable to clinical practice is lacking or limited; and 3) designing more
      effective dissemination tools making relevant research findings more easily
      accessible and part of every day practice. CONCLUSIONS: Variations in practice
      patterns, difficulties in keeping current with the scientific literature, and
      providing students with knowledge, skills, and competencies necessary for
      contemporary practice are challenges facing the health care professions today,
      including dental hygiene. To address these problems, an evidence-based approach
      has been recommended by national organizations. This paper reviews the issues and
      proposes a model and strategies for engaging dental hygiene clinicians,
      educators, and researchers in EBDM. Those involved in each area will need
      training in EBDM concepts and skills before this approach can be fully integrated
      into education and practice or used to guide research activities. National
      leadership will be needed to coordinate and prioritize research strategies,
      promote curricular changes, and improve access to clinically relevant information
      so that an EBDM approach can become the norm in practice.

PMID- 11314228
TI  - Do you know if your patients, co-workers, friends, family, or you have an
      addiction?
AB  - Substance abuse (chemical dependence) is often a silent, but pervasive problem in
      today's society. Chemically dependent people come from all components of society,
      regardless of financial status, ethnicity, or age. They are masters at disguising
      their addictions. A variety of chemicals, including over-the-counter,
      prescription, and street drugs are used and abused. Dopamine, a neurotransmitter
      in the brain, appears to be the major determinant in whether or not a person
      progresses from casual substance use to substance abuse. This course will discuss
      commonly abused types of substances, signs of substance use (psychological,
      physiological, oral manifestations), and the role of dopamine in the addiction
      process. An outline of successful interventions and preventive strategies will be
      included. Because health care professionals should be aware of the many aspects
      of substance abuse, this course is designed to increase understanding of the
      clinical and social aspects of the problem. It will provide information to help a
      patient, co-worker, or family member manage this debilitating and complicated
      problem.

PMID- 11314229
TI  - The importance of ethology in understanding the behaviour of the horse.
AB  - Domestication has provided the horse with food, shelter, veterinary care and
      protection, allowing individuals an increased chance of survival. However, the
      restriction of movement, limited breeding opportunities and a requirement to
      expend energy, for the benefit of another species, conflict with the evolutionary
      processes which shaped the behaviour of its predecessors. The behaviour of the
      horse is defined by its niche as a social prey species but many of the traits
      which ensured the survival of its ancestors are difficult to accommodate in the
      domestic environment. There has been a long association between horses and man
      and many features of equine behaviour suggest a predisposition to interspecific
      cooperation. However, the importance of dominance in human understanding of
      social systems has tended to overemphasize its importance in the human-horse
      relationship. The evolving horse-human relationship from predation to
      companionship, has resulted in serial conflicts of interest for equine and human
      participants. Only by understanding the nature and origin of these conflicts can
      ethologists encourage equine management practices which minimise deleterious
      effects on the behaviour of the horse.

PMID- 11314230
TI  - Understanding equine stereotypies.
AB  - It is frequently asserted that equine stereotypies, such as crib-biting, wind
      sucking and weaving, are caused by boredom. However, this explanation is too
      general to be of practical use in discerning the causes of each stereotypy or in
      devising management practices to prevent their occurrence. The majority of equine
      stereotypes start within one month of weaning when both the nutritional and
      social environment of the foal are substantially altered. Epidemiological
      research has revealed that the provision of low quantities of forage and minimal
      opportunities for social contact are associated with a higher reported prevalence
      of stereotypic behaviour. Experimental data also suggest that oral stereotypies
      develop in response to a low forage diet but this may be partially adaptative.
      Oral stereotypies may increase salivary flow therefore reducing the acidity of
      gastric tract and speeding the transit of ingested feed. Stereotypic horses may
      be less reactive to short-term aversive stimulation. Neither direct nor
      circumstantial evidence confirms anecdotal reports that horses copy stereotypies
      from each other. Surgical and pharmacological methods of prevention should not be
      attempted unless the underlying causes are removed.

PMID- 11314231
TI  - The development of equestrianism from the baroque period to the present day and
      its consequences for the welfare of horses.
AB  - Many saddle horses are slaughtered at a young age which could be indicative of a
      welfare problem. Bad riding is probably an underestimated source of poor welfare.
      Widespread knowledge of 'academic' riding should be encouraged and should be
      beneficial to all horses, at all schooling levels, for all purposes. In
      particular, 18th century principles tend to be forgotten and in this article the
      authors illustrate some differences to modern dressage. Various suggestions are
      made in order to improve welfare.

PMID- 11314232
TI  - Horses and the rural economy in the United Kingdom.
AB  - The horse industry is large and varied, but until comparatively recently its
      contribution to the economy of the UK has been virtually ignored and this,
      together with the disparate nature and small size of the individual businesses
      involved, has resulted in a general lack of universally available data. What is
      undoubtedly true, however, is that the horse touches upon the professional and
      recreational aspects of many peoples' lives and that, without the horse, not only
      would a significant proportion of the rural working population be unemployed but
      many ancillary industries would have considerably less work available. This paper
      reinforces the concept of the horse being at the centre of a large, though
      disparate and dispersed industry and, what is more, that it is an industry of
      essential importance both to the welfare of the countryside and to the economic
      viability of the UK. It also attempts to quantify the size of the horse industry
      based upon limited information. The paper concludes that 125,000 people
      (expressed in full time equivalents) are employed directly, there are 600,000
      horses and an economic contribution in excess of 1000 m Pounds.

PMID- 11314233
TI  - Perceptions and attitudes towards horses in European societies.
AB  - In spite of the fact that horses were domesticated between 5000 and 3000 B.C.,
      the relations between humans and horses constitutes a relatively unexplored area.
      This may be due to the fact that horses in middle class western society are seen
      as companion animals, of primarily social and recreational value. Horses,
      however, have historically enjoyed an enormously important utilitarian, economic
      and sporting significance and in many countries horse meat is also eaten.
      Nowadays, we can classify the different ways in which horses are used into four
      different fields: recreational and/or social purposes breeding sport and
      competition meat production In each category one can distinguish 4 main areas of
      concern: the behaviour and wellbeing of the horse feeding maintenance veterinary
      care All 4 fields make their own particular demands on these aspects of the care
      of horses. In addition, people have also approached these different fields of
      equine exploitation through the centuries with different attitudes. The goal of
      this article is to review the attitudes of people towards horses. The main
      conclusion of this article is that the diversity of uses for equines and
      corresponding organisations makes it difficult to get a clear overview and
      thereby inhibits scientific research into human-horse interactions.

PMID- 11314234
TI  - The human-horse relationship: how much do we know?
AB  - Human relationships or interactions with horses have varied throughout history
      depending on human needs, but it is horses' ability to carry a human individual
      that has had perhaps the greatest impact on their relationship with man. Despite
      our long association with the horse, there have been few studies on human-horse
      relationships. There is little historical evidence on individual relationships
      with horses but indications of strong human-horse relationships have been noted
      in mounted societies, such as North American Plains Indians. Riding a horse has
      traditionally been associated with power, and was reserved for the ruling elite
      in many areas. Demographic data suggest that human relationships with horses may
      have changed in recent times. Although the lack of land and the relatively high
      cost of horse care may reduce the possibility of ownership for many people, the
      availability of riding establishments and increases in leisure time mean that
      riding is no longer restricted to the upper classes. There is a wide range in
      type and intensity of potential interactions with horses, indicating that human
      horse relationships are likely to vary considerably. Some people appear to
      sacrifice a great deal in order to own a horse. However, the motivation behind
      these activities and the process by which an individual assesses personal costs
      of ownership versus their perceived benefits remains to be studied. Future
      research should focus on characterising the human-horse relationship, and the
      degree of individual and cultural variation. A greater understanding of horse
      owner perceptions of 'costs' versus 'benefits' may also increase our
      understanding of the relationship and the economic importance of horses in
      society.

PMID- 11314235
TI  - Review of equine feeding and stable management practices in the UK concentrating
      on the last decade of the 20th century.
AB  - Equine feeding and stable management practices for horses kept in the UK vary
      greatly and it is probable that almost any permutation of regimen could be found
      somewhere. Unfortunately, there is uncertainty about the number of horses in the
      UK and very limited data are available on the ways horses are being fed and
      managed. This paper reviews some of the information that is available and
      provides an outline of some of the factors influencing the practices used. To a
      certain extent, the way UK horses are fed and managed primarily reflects the
      purpose for which they are kept (e.g. racing Thoroughbred vs. native breeding
      pony) as well as their location (urban vs. rural); the time of year; their
      breed/age as well as the owner's financial situation. In very general terms, the
      various ways that horses can be kept and managed fall between 2 extremes: the
      professional riders/owners/trainers who tend to keep horses and ponies either in
      large barns/stable yards managed by themselves or a head stable person and the
      more amateur competitor/leisure riders who tend to keep their horses at a livery
      yard or at their own or a friend's home. Many of these animals are kept under
      either part or full do-it-yourself (DIY) conditions. Common feeding practices
      range from feeding traditional home cereal-based mixes to feeding coarse
      mixes/pelleted compound manufactured feeds. Very few people, however, feed just a
      simple single grain or compound feed plus roughage diet. Many add other separate
      feeding stuffs and supplements including soaked sugar beet or straight molasses,
      primarily as palatability enhancers. Other common additions include cod liver
      oil, various types of vegetable oil, carrots, one or more vitamin/mineral mixes,
      herbal mixes and certain agents with ergogenic/performance-enhancing claims.
      Especially for horses used for competition purposes, provision of supplementary
      salt is common either by means of a salt block or lick or as an addition to the
      feed. The soaking of hay, for a variable time period, is another common practice.
      Although the type and amount of feed fed fundamentally varies according to the
      work load of the horse there tends to be marked seasonal variations in feeding
      practices due to the weather and the availability of pasture.

PMID- 11314236
TI  - Investigating the origins of horse domestication.
AB  - Before the development of firearms, the horse was crucial to warfare and, before
      the invention of the steam engine, it was the fastest and most reliable form of
      land transport. It is crucial to the life of nomadic pastoralists on the Eurasian
      steppe and played a major role in the evolution of human society during the
      Bronze Age and Iron Age. Understanding the human past requires knowledge of the
      origins and development of horse husbandry. The problem of being able to identify
      the early stages of horse domestication is one that many researchers have
      grappled with for the most part unsuccessfully. Until recently the most important
      criteria used had been that of increased relative abundance. That is, around 3500
      BC, in some parts of Eurasia, there was an apparent increase in the proportions
      of horse bones and teeth found in archaeological deposits by comparison with
      preceding periods. However, other evidence suggests that the observed increase
      during the Copper Age could be explained as well, or even better, by increased
      hunting rather than by domestication.

PMID- 11314237
TI  - Virgin olive oil phenolic compounds: binding to human low density lipoprotein
      (LDL) and effect on LDL oxidation.
AB  - Oxidation of low density lipoproteins (LDL) appears to occur predominantly in
      arterial intima in microdomains sequestered from antioxidants of plasma.
      Therefore phenolic compounds which are able to bind LDL are good drug candidates
      for the effective prevention of lipid peroxidation and atherosclerotic processes.
      Plasma from healthy volunteers on nonsupplemented diets was incubated with virgin
      olive oil phenolic extracts (0-200 mg/l, caffeic acid equivalents). Phenolic
      compounds in LDL were measured by high-performance liquid chromatography-diode
      array detection (HPLC-DAD). Copper-mediated LDL oxidation was performed, and
      conjugated dienes formation was monitored. After plasma preincubation with olive
      oil phenolic compounds (OOPC), an increased OOPC-concentration dependent was
      observed in the total phenolic content of LDL (p < 0.001, ANOVA) as well as in
      the lag time before conjugated diene formation (p < 0.001, ANOVA). Rutin and four
      phenolics with flavonoid-like spectra were found to be bound to the LDL control.
      These phenolics, together with tyrosol which was not present in the LDL control,
      significantly increased in LDL (p < 0.05) after plasma incubation with OOPC.
      These results show the ability of tyrosol to bind LDL in vitro and the capacity
      of virgin olive oil phenolics to protect other phenolic compounds previously
      bound to LDL. These results provide further evidence that phenolic compounds
      bound to LDL are likely to protect LDL from oxidation.

PMID- 11314238
TI  - Oral rehydration solution containing rice maltodextrins in patients with total
      colectomy and high intestinal output.
AB  - Oral rehydration solutions containing rice maltodextrins (R-ORS) have been
      reported to be more effective than glucose-based ORS in reducing intestinal
      losses in infectious diarrhea. To evaluate the effect of R-ORS in patients with
      total colectomy and high intestinal output, a perspective open noncontrolled
      study was performed on 13 adult patients who consumed 1 l/day of R-ORS for 7
      days. Body weight, daily ileal and urinary output, serum electrolytes,
      aldosterone and renin activity were measured the day before (day 0) and on the
      last day of the study (day 7). Net changes (mean +/- SE) from day 0-7 showed an
      increase of urine Na (40 +/- 16 mmol/day, p < 0.04) and K (24 +/- 8 mmol/day, p <
      0.02). Body weight increased in seven patients. Serum renin activity decreased (
      0.60 +/- 0.26 ng/ml/min) in these patients but not in the six patients in whom
      body weight remained unchanged (0.19 +/- 0.07 ng/ml/min; p < 0.03). Ileal and
      urinary volume remained stable. In patients with high ileal output, R-ORS
      supplementation improved Na and K balance. The association of increased body
      weight with decreased serum renin concentrations suggests that a positive water
      balance also occurred.

PMID- 11314240
TI  - Scalp psoriasis: topical calcipotriol 50 micrograms/g/ml solution vs.
      betamethasone valerate 1% lotion.
AB  - Forty-two patients aged between 6 and 61 years (mean: 33.5 years) with psoriasis
      of the scalp were enrolled in this study. Twenty-seven patients (69%) were males
      and 15 (31%) were females. The aim of our study was to evaluate the efficacy,
      safety and tolerability of topical calcipotriol 50 micrograms/g/ml solution vs.
      betamethasone valerate 1% lotion in the treatment of psoriasis of the scalp. The
      study was randomized with the twice-daily application of either calcipotriol
      solution or betamethasone valerate lotion for 6 weeks. Treatment evaluation was
      clinically based on signs of psoriasis (thickness, redness, scaliness) which were
      scored from 0 = absent to 4 = severest possible involvement and was performed at
      the start of treatment and at weeks 2 and 6 of treatment. The results showed a
      marked improvement and clearance at the end of treatment in 15 (72.8%) of the 24
      patients in the calcipotriol group and in 13 of the 18 patients (72%) in the
      betamethasone group. The mean total sign score at baseline was 5.1 in the
      calcipotriol group and 5.4 in the betamethasone valerate group. At the end of
      treatment, this score was decreased to 2.1 and 1.49, respectively. No significant
      adverse effects were reported in either group except in two patients (8.3%) in
      the calcipotriol group who developed signs of irritation including itching and
      erythema. In conclusion, both drugs were effective and well tolerated in the
      treatment of scalp psoriasis but in some patients calcipotriol had to be given
      for more prolonged courses.

PMID- 11314239
TI  - Prevention with clodronate of osteoporosis secondary to inhaled corticosteroid
      treatment in patients with chronic asthmatic bronchitis.
AB  - Steroid therapy is the third most common cause of osteoporosis, after loss of
      gonad function and senescence. The aim of the present study was to evaluate the
      protective action of clodronate on bone mass loss induced by steroid therapy.
      Sixty patients with bronchial asthma receiving either fluticasone (250 mg x
      4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were
      enrolled. Half the patients received combination treatment with clodronate (100
      mg i.m./14 days), for a total period of 12 months. All patients were evaluated at
      baseline and at the end of treatment for bone mineral density (BMD) and
      calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia,
      phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The
      results of this preliminary study confirm the protective influence of clodronate
      on bone mass loss, as documented by the increment in mean values in BMD reported
      at the end of treatment compared with baseline values.

PMID- 11314241
TI  - Mud bath therapy influences nitric oxide, myeloperoxidase and glutathione
      peroxidase serum levels in arthritic patients.
AB  - Nitric oxide (NO) has recently been proposed as an important mediator in
      inflammatory phases and in loss of cartilage. In inflammatory arthritis NO levels
      are correlated with disease activity and articular cartilage is able to produce
      large amounts of NO with the appropriate inducing factors such as cytokines
      and/or endotoxin. Neutrophils also play an important role in inflammatory
      reactions and the level of myeloperoxidase, a constituent of neutrophil granules,
      is related to the intensity of the inflammation. Because there is evidence that
      suggests that mud packs influence the main cytokines involved in cartilage
      damage, we tried to determine whether NO and myeloperoxidase are involved in the
      mechanisms of action of mud bath treatment. We enrolled 37 subjects and randomly
      assigned them to two groups: 19 patients underwent mud bath treatment (group A)
      while 18 patients underwent bath treatment alone. Blood samples were obtained
      before and after the treatment cycles to assay serum levels of NO,
      myeloperoxidase (MPO) and glutathione (GSH)-peroxidase. The results showed a
      statistically significant decrease in NO and myeloperoxidase serum values in
      groups A and B, while GSH-peroxidase was not significantly increase in either of
      the groups; no correlation was found between NO, myeloperoxidase and GSH
      peroxidase serum values. Mud bath treatment can exert beneficial effects on
      cartilage homeostasis and inflammatory reactions, influencing NO and decreasing
      myeloperoxidase serum values. The increase in GSH-peroxidase was not correlated
      with the reduction of other biochemical markers, suggesting that mud bath
      treatment has different mechanisms of action.

PMID- 11314243
TI  - Production, purification and some properties of Bac201, a bacteriocin-like
      inhibitory substance produced by Staphylococcus aureus AB201.
AB  - Staphylococcus aureus AB201, a clinical isolate from wound pus, produced a
      bacteriocin-like inhibitory substance termed as Bac201, that was inhibitory to
      Streptococcus agalactiae, Enterococcus faecalis, Acinetobacter calcoaceticus,
      Neisseria meningitidis and a number of staphylococcal species. It was purified to
      homogeneity by ammonium sulfate precipitation, gel filtration (BioSil-SEC-125),
      and reversed-phase high performance liquid chromatography (Vydac C4). The native
      Bac201 was sized at approximately 170-kDa as determined by GF HPLC. Fraction-I
      (native Bac201), having antibacterial activity was also examined by transmission
      electron microscopy and appeared as globular structure showing resemblance with
      phage-like objects. The purification of Bac201 resulted in 466-fold increase in
      specific activity and recovery of 0.94% of total antibacterial activity. The
      purified Bac201 migrated as single band on SDS-PAGE with an estimated molecular
      mass of about 41-kDa. Bac201 was sensitive to proteolytic enzymes, resistant to
      heat and organic solvents, and active over a wide range of pH (2.5-10). The amino
      acid composition revealed a general resemblance with other reported high
      molecular mass bacteriocins and predominance of glycine (39%), proline (13%) and
      alanine (8%) residues. Further results showed that Bac201 has a bactericidal
      effect on sensitive cells which is not produced by either cell lysis or apparent
      loss of membrane permeability.

PMID- 11314242
TI  - Amplification of the Escherichia coli lacZ gene in Bacillus subtilis and its
      expression on a by-product growth medium.
AB  - A Bacillus subtilis wild type strain and a kinA (spoIIJ) isogenic mutant were
      compared as hosts for the expression of the Escherichia coli beta-galactosidase
      gene, lacZ, driven by the B. subtilis aprE promoter in a chromosomal system. The
      2 x SG sporulation formula, with some modifications, was used as a basal medium.
      The specific activity values recorded by the mutant strain at the stationary
      phase were markedly higher than those achieved by the wild type host. Exposure of
      the cells to increasing levels of chloramphenicol resulted in significant
      amplifications of the lacZ region. Gene copy numbers of 19 and 11 were estimated
      in the amplified wild type and kinA strains, respectively, with high
      segregational stability records. The magnitude of beta-galactosidase over
      expression was dependent on, and roughly proportional to antibiotic resistance
      levels. Among five examined by-products, a 2.3-times diluted concentration of
      neutralized cheese whey was successfully used as a sole medium component for over
      expression of the recombinant beta-galactosidase gene in B. subtilis.

PMID- 11314244
TI  - Specificity of lectin activity of Bacillus thuringiensis parasporal inclusion
      proteins.
AB  - Sheep erythrocyte-agglutinating parasporal inclusion proteins from four Bacillus
      thuringiensis strains (FITC-20, FITC-73, FITC-76 and IBC-1456) were examined for
      lectin activity against erythrocytes from four mammalian (rabbit, horse, cow and
      guinea pig) and an avian (chicken) species. Of the five erythrocyte species, only
      rabbit cells were agglutinated with the protein of the human cancer cell-killing
      strain IBC-1456. No haemagglutination (HA) activities were shown in other protein
      erythrocyte combinations. The lectin activity of the strain IBC-1456 against
      rabbit cells was strongly inhibited by preincubation with D-galactose. Overall
      results revealed that the B. thuringiensis lectins have a preference for sheep
      erythrocytes.

PMID- 11314245
TI  - Binding of heme by Gardnerella vaginalis.
AB  - It has been previously demonstrated that Gardnerella vaginalis could acquire iron
      from a number of different iron-containing compounds, including heme. In this
      study, the direct binding of heme by G. vaginalis strains was demonstrated
      utilizing a liquid broth heme-binding assay. Competition studies demonstrated
      that pretreatment of G. vaginalis cells with other iron sources such as
      hemoglobin, catalase, and lactoferrin did not affect heme binding. Also, heme
      binding was not inhibited by preincubation of G. vaginalis cells with
      protoporphyrin IX. Two potential heme-binding proteins with estimated molecular
      weights of 30 and 70 kDa were isolated using heme-agarose batch affinity
      chromatography.

PMID- 11314246
TI  - The entomopathogenic potential of Aspergillus spp. in mosquitoes vectors of
      tropical diseases.
AB  - Eleven strains of the most frequent Aspergillus species found in a survey of
      Brazilian mosquitoes collected in the states of Minas Gerais and Rio de Janeiro,
      Brazil, were used for bioassays in second-stage larvae of Aedes fluviatilis and
      Culex quinquefasciatus. Aspergillus ochraceus, A. kanagawaensis and one strain of
      A. sulphureus were most effective, causing mortality in at least 80% of the
      larvae of the two mosquito species tested. Variations in entomopathogenic
      capacity were observed in the experiments with strains of A. sulphureus, A.
      flavus and A. ochraceus.

PMID- 11314247
TI  - Identification of geosmin as a volatile metabolite of Anabaena sp.
AB  - A cyanobacterial isolate recovered from Lake Ogletree, the principal drinking
      water supply for the city of Auburn, Alabama (USA) was identified as Anabaena sp.
      The isolate was shown to produce the most common off-flavor compound, geosmin.

PMID- 11314248
TI  - Production of alpha-amylase with Aspergillus flavus on Amaranthus grains by solid
      state fermentation.
AB  - The effects of the ingredients of the Rajgeera (Amaranthus paniculatas) medium
      designed for production by A. flavus was evaluated with the help of the
      fractional factorial method, 'The Plackett-Burman' design. Out of the fifteen
      medium components used in the design, four components, viz., corn steep liquor,
      ammonium hydrogen phosphate, sodium chloride and calcium chloride were selected
      based on the contrast coefficient values and further used as independent
      variables in the 'Box-Behnken' design. A polynomial multiple regression model was
      generated using the SPSS/PC + (version 7.5) statistical analysis package. Corn
      steep liquor, ammonium hydrogen phosphate, sodium chloride and calcium chloride
      contributed to the yield to the tune of 81.3% of which sodium chloride and
      calcium chloride affected the yield to the tune of 68.3%. The yield obtained from
      the optimized medium was 8 times that obtained from the original medium.
      Amaranthus paniculatas grains as a source of starch and carbon for production of
      alpha-amylase under solid-state fermentation has been studied for the first time.

PMID- 11314249
TI  - Natural zeolite clinoptilolite increases the concentrations of sphingoid bases in
      the yeast Yarrowia lipolytica.
AB  - In the present paper, we studied the effect of natural zeolite clinoptilolite on
      sphingolipid metabolism in the yeast Yarrowia lipolytica. We also investigated if
      zeolite addition had any impact on cell shape and size, as well as on the pH
      alterations during the culture growth. High performance liquid chromatography
      analysis of sphingoid bases obtained by acid hydrolysis of complex sphingolipids
      from Y. lipolytica showed that their concentrations markedly rose upon the
      zeolite addition. The largest increase among the identified molecular species of
      sphingoid bases was seen in C18 phytosphingosine, whose levels rose 6.2-fold and
      22.3-fold after culturing cells for 24 and 36 hours respectively in the presence
      of finely ground zeolite. pH measurements of the culture medium showed a
      similarity between pH profiles of control and zeolite-supplemented cells,
      suggesting that ion-exchange capacity was not probably responsible for the
      observed change in sphingolipid metabolism. Scanning electron microscopy revealed
      that zeolite affected cell size and shape. Y. lipolytica cells grown in the
      absence of zeolite were oval-shaped with an average cell size of 0.7-2.7 microns,
      whereas when cultured with zeolite, they were round-shaped and larger, having an
      average cell size of 1.3-2.9 microns.

PMID- 11314250
TI  - DNA amplification fingerprinting using two long primers.

PMID- 11314251
TI  - New series of vectors for phage display and prokaryotic expression of proteins.

PMID- 11314252
TI  - A Snafu in SNP analysis in a member of a multigene family.

PMID- 11314253
TI  - Small bones from dried mammal museum specimens as a reliable source of DNA.

PMID- 11314254
TI  - Copacabana method for spreading E. coli and yeast colonies.

PMID- 11314255
TI  - Incorporation of sodium sulfite into extraction protocol minimizes degradation of
      Acacia DNA.

PMID- 11314256
TI  - Use of inexpensive dyes to calibrate and adjust your microarray printer.

PMID- 11314257
TI  - Channel surfing: creating different color combinations from multiple-label
      images.

PMID- 11314258
TI  - Recovering filter-based microarray data for pathways analysis using a multipoint
      alignment strategy.
AB  - The use of commercial microarrays is rapidly becoming the method of choice for
      profiling gene expression and assessing various disease states. Research Genetics
      has provided a series of biological and software tools to the research community
      for these analyses. The fidelity of data analysis using these tools is dependent
      on a series of well-defined reference control points in the array. During the
      course of our investigations, it became apparent that in some instances the
      reference control points that are required for analysis became lost in background
      noise. This effectively halted the analysis and the recovery of any information
      contained within that experiment. To recover this data and to increase analytical
      veracity, the simple strategy of superimposing a template of reference control
      points onto the experimental array was developed. The utility of this tool is
      established in this communication.

PMID- 11314259
TI  - PCR-based RNA probes: a quick and sensitive method to improve whole mount embryo
      in situ hybridizations.
AB  - We have developed a PCR-based technique for the preparation of RNA probes that
      can be used for whole mount in situ hybridization on embryos. T3 or T7 RNA
      polymerase promoters were introduced at the 5' end of gene-specific
      oligonucleotide primers enabling direct in vitro transcription of purified PCR
      fragments. We show for various marker genes in Xenopus embryos that this method
      provides equivalent results as compared to conventional vector-based probe
      preparation, even when fluorescence detection (FISH) is applied. This method
      offers a rapid and useful means to prepare gene-specific in situ probes
      predominantly for expression screens or detection of splice variants that
      previously required time-consuming cloning steps.

PMID- 11314260
TI  - Enhanced detection of beta-galactosidase reporter activation is achieved by a
      reduction of hemoglobin content in tissue lysates.
AB  - beta-galactosidase (beta-gal), the product of the E. coli LacZ gene, has been
      used extensively as a reporter in numerous systems. Until recently, the most
      commonly used method of detecting beta-gal reporter enzymatic activity was a
      colormetric assay based on the cleavage of the beta-gal substrate 5-bromo-4
      chloro-3-indolyl beta-D-galactopyranoside (X-gal) to form a blue precipitate.
      However, when increased sensitivity is needed, many investigators now turn to
      alternate substrates that produce fluorescent or luminescent products upon
      cleavage by beta-gal. These products are much more easily quantified than X-gal.
      The luminescent and fluorometric assays work very well in cultured cells but are
      often less sensitive in whole tissue lysates. In this study, we have evaluated
      the sensitivity of a fluorescent and a luminescent substrate in whole tissue
      lysates cleared of red blood cells or washed with PBS only. We have found that
      both assays show increased low-end sensitivity in tissues with reduced levels of
      hemoglobin (Hb). Hb is apparently able to quench luminescent and, to a lesser
      degree, fluorescent reporter light emission. Therefore, steps should be taken to
      reduce Hb levels either by lysis, perfusion, or both to enhance the sensitivity
      of these assays.

PMID- 11314261
TI  - Specific inhibitors prevent proteolytic degradation of recombinant proteins
      expressed in High Five cells.
AB  - The insect cell line BTI-TN-5B1-4 (High Five) is frequently used to express
      recombinant proteins in large amounts using the baculovirus expression system.
      However, extensive proteolytic degradation of recombinant proteins is often
      encountered. Furthermore, we have observed that recombinant proteins migrate in
      SDS-PAGE in agreement with poly-ubiquitinated forms of the protein, suggesting a
      ubiquitin/proteasome degradation pathway. Here, we describe a systematic study
      unraveling the effect of adding proteasome inhibitors or specific protease
      inhibitors to the growth medium of High Five insect cells infected with
      recombinant baculovirus. Furthermore, protease inhibitors were added to the lysis
      buffer to establish the most efficient way to inhibit proteolytic activity after
      lysis of baculovirus-infected cells expressing recombinant proteins. We conclude
      that a combination of adding protease inhibitors to the growth medium and to the
      lysis buffer minimizes the proteolytic activity in High Five cells. The most
      efficient protease inhibitors were E-64 in the growth medium together with
      Leupeptin in the lysis buffer at concentrations higher than with available
      cocktails of inhibitors. The optimal treatment of High Five cells is different
      from the optimal treatment of Sf9 cells. For proteins susceptible to
      ubiquitinylation, a treatment of insect cell cultures with the proteasome
      inhibitor MG132 (LLL) leads to a considerable reduction of the yield of
      production of recombinant protein.

PMID- 11314262
TI  - Photobleaching of arterial autofluorescence for immunofluorescence applications.
AB  - Immunohistochemical localization of low-level antigens in the arterial
      vasculature is complicated by the presence of complex molecules such as collagen,
      elastin, cholesterol, and fluorescent lipids that exhibit autofluorescence over a
      wide spectrum of wavelengths. UV irradiation of arterial vasculature has remained
      ineffective in preparing samples for immunofluorescent staining because of the
      recovery of the endogenous fluorescence within a short time following treatment.
      Therefore, we sought to further enhance the signal-to-noise ratio in arteries by
      optimizing the photobleaching of this tissue. We report here that the use of
      filtered sunlight significantly reduces arterial autofluorescence compared to
      standard UV shortwave and longwave irradiation and maintains multiple antigen
      epitopes suitable for immunohistochemical analysis. Using this method, we
      localized low-level laminin-5 isoform expression in situ, which was previously
      indistinguishable from endogenous autofluorescence.

PMID- 11314263
TI  - Specific blocking to improve biopanning in biological samples such as serum and
      hybridoma supernatants.
AB  - Screening phage-displayed peptide libraries (biopanning) is an important
      technique for acquiring peptide ligands and for mapping peptide epitopes
      recognized by antibodies (Ab). In biological samples, other materials, not only
      contaminants but also natural constituents, often interfere with biopanning.
      Capture methods use anchoring Abs that reduce the need for purification of the
      intended panning target from a crude sample. This capture method is analogous to
      sandwich ELISA. However, when the target molecule concentration is low in the
      initial mixture, the panning of a captured target often yields epitopes that bind
      to the capture antibody rather than the target of interest. We have developed a
      methodology that utilizes specific blocking reagents of the capture Ab to extend
      the sensitivity and applicability of the capture approach to phage panning. A
      flowchart is presented to enable the worker to begin panning with the simplest
      approach and then to employ sandwich capture and specific blocking reagents as
      necessary.

PMID- 11314265
TI  - Genetic transformation of yeast.
AB  - Genetic transformation was first described by Griffith in 1928 and has since been
      demonstrated in a variety of organisms, including many species of fungi. This
      review focuses on the history and technology of the transformation of
      Saccharomyces cerevisiae. The application of protocols developed for S.
      cerevisiae to other important yeast species is discussed. The protocols for
      transformation by spheroplasting, LiAc/ssDNA/PEG, and electroporation are
      compared, and possible mechanisms for transformation are discussed.

PMID- 11314264
TI  - Measurement of mitochondrial pH in situ.
AB  - In this article, we describe the advantages and disadvantages of procedures for
      monitoring mitochondrial pH in situ using optical microscopic techniques. The
      first method employs the combination of the fluorescent pH-sensitive indicator
      carboxy-SNARF and laser scanning confocal microscopy. Manipulation of the loading
      and post-loading conditions enables relatively specific accumulation of carboxy
      SNARF into mitochondria. With the use of a mitochondrial-specific marker,
      mitochondrial pH can be accurately monitored. More recently, mitochondrial
      targeted, pH-sensitive probes have been used to monitor mitochondrial pH. In
      particular, mitochondrial targeting of the yellow fluorescent protein (YFP)
      mutant of green fluorescent protein (GFP) combines the advantages of specific
      mitochondrial localization, high-fluorophore quantum yield, and extinction
      coefficient with an appropriate pKa for measuring mitochondrial pH. The use of
      dual-excitation ratiometry with mitochondrially targeted YFP increases the
      dynamic range of mitochondrial pH measurements and corrects for differences in
      the amount of expression of mitochondrially targeted YFP at the level of
      individual mitochondria.

PMID- 11314266
TI  - Dual-label detection of amplified products in quantitative RT-PCR assay using
      lanthanide-labeled probes.
AB  - Quantitative RT-PCR (QRT-PCR) enables the sensitive and specific detection of
      mRNA with a small copy number. We used the QRT-PCR method and dual-label analysis
      of amplification products for the detection of prostate-specific antigen (PSA)
      mRNA. The QRT-PCR assay employed a PSA-like internal standard (IS) mRNA, which
      was used to quantify the PSA mRNA copies and to control the variations during the
      whole assay procedure from the RNA extraction to the detection of QRT-PCR
      amplification products by hybridization assay. After co-amplification, the PSA
      and IS products were detected in a microplate using Eu3+ chelate-labeled PSA and
      Tb3+ chelate-labeled IS hybridization probes. The detection probes allowed the
      simultaneous and dual-label detection of PSA and IS products in the same
      microtiter well. Compared to the single-label assay, the dual-label detection
      improved the within- and between-assay CV% from 21.7 to 7.5 and from 36.0 to
      30.3, respectively. The between- and within-assay variation of the dual-label
      assay was further studied using PSA-producing LNCaP cells. The cells were found
      to express 980 +/- 170 (mean +/- SD) copies of PSA-mRNA with the within-assay CV%
      of 17.7 and 890 +/- 220 (mean +/- SD) copies of PSA-mRNA with the between-assay
      CV% of 25.0. The methodology developed may help in future studies to obtain
      reliable quantification of PSA mRNA generated by circulating prostate cancer
      cells.

PMID- 11314267
TI  - Continuous spectrophotometric assay for beta-glucuronidase.
AB  - A continuous spectrophotometric assay has been developed for detecting beta
      glucuronidase activity. In the assay, Para-nitrophenyl beta-D-glucuronide is
      cleaved to yield a chromophoric product. With the commercial E. coli enzyme, it
      is demonstrated that the reactions can be continuously monitored by the increase
      of absorbance at 405 nm. The method is highly sensitive and able to detect less
      than 1.4 x 10(-4) U/mL of the enzyme activity in solution. Such a new assay
      offers significant advantages over the existing discontinuous methods and should
      be useful for both routine enzyme assay and accurate kinetic studies.

PMID- 11314268
TI  - Isothermal amplification and multimerization of DNA by Bst DNA polymerase.
AB  - We have demonstrated the isothermal in vitro amplification and multimerization of
      several different linear DNA targets using only two primers and the strongly
      strand-displacing exonuclease-negative Bst DNA polymerase. This reaction has been
      termed linear target isothermal multimerization and amplification (LIMA). LIMA
      has been compared with cascade rolling-circle amplification and has been found to
      be less sensitive but to yield similar variable-length multimeric dsDNA
      molecules. Products from several different LIMA reactions were characterized by
      restriction analysis and partial sequence determination. They were found to be
      multimers of subsets of the target sequence and were not purely primer derived.
      The sensitivities with respect to target concentration of several different LIMA
      reactions were determined, and they varied from 0.01 amol to 1 fmol. The
      sensitivity and specificity of LIMA were further tested using E. coli genomic
      DNA, and the selective amplification of a transposon fragment was demonstrated. A
      successful strategy for reducing LIMA-dependent background DNA synthesis in
      rolling-circle amplification embodiments was devised. This entailed the affinity
      purification of circular DNA templates before amplification.

PMID- 11314269
TI  - Template selection during manipulation of complex mixtures by PCR.
AB  - PCR is ubiquitous in molecular biology. It is used to amplify single sequences
      from large genomes, or populations of sequences from complex mixtures such as
      cDNA libraries in mammalian cells. These cDNA libraries are often employed in
      subsequent labor-intensive experiments such as genetic screens, the outcome of
      which depends on library quality. The use of PCR to amplify diverse sequence
      populations raises important technical issues. One question is whether or not PCR
      is capable of maintaining population diversity, specifically with respect to
      template selection in the first rounds of the amplification process (i.e., the
      possibility that rare sequences in a complex mixture are lost because of
      amplification failure at the outset of the PCR). Here, we analyze the properties
      of PCR in the context of template selection in complex mixtures and show that it
      is an excellent method for preserving diversity.

PMID- 11314270
TI  - Modification of an automated liquid-handling system for reagent-jet, nanoliter
      level dispensing.
AB  - Reducing the scale of biochemical reactions is becoming commonplace. Examples
      include the screening of large libraries of chemical compounds or gene sequences.
      These applications demand the ability to transfer sub-microliter volumes of
      fluid. To this end, we have modified a Hamilton MICROLAB 2200 with high-speed
      solenoids and a liquid pressurization system to modulate volume delivery down to
      the nanoliter level. Additional modifications include the use of sapphire-tipped
      dispensing nozzles and a high-resolution substage to assist in the construction
      of DNA microarrays. Techniques for characterizing the dispensed volume are
      presented.

PMID- 11314271
TI  - Poly (ADP-ribose) polymerase cleavage monitored in situ in apoptotic cells.
AB  - During apoptosis, the activation of a family of cysteine proteases, or caspases,
      results in proteolytic cleavage of numerous substrates. Antibody probes specific
      for neoepitopes on protein fragments generated by caspase cleavage provide a
      means to monitor caspase activity at the level of the individual cell. Poly (ADP
      ribose) polymerase (PARP), a nuclear enzyme involved in DNA repair, is a well
      known substrate for caspase-3 cleavage during apoptosis. Its cleavage is
      considered to be a hallmark of apoptosis. Here, we demonstrate that an affinity
      purified polyclonal antibody to the p85 fragment of PARP is specific for
      apoptotic cells. Western blots show that the antibody recognizes the 85-kDa (p85)
      fragment of PARP but not full-length PARP. We demonstrate a time course of PARP
      cleavage and DNA fragmentation in situ using the PARP p85 fragment antibody and
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in
      Jurkat cells treated with anti-Fas. Furthermore, our results indicate that the
      p85 fragment of PARP resulting from caspase cleavage during apoptosis is rapidly
      localized outside the condensed chromatin but not in the cytoplasm.

PMID- 11314272
TI  - Reverse transcriptase template switching: a SMART approach for full-length cDNA
      library construction.
AB  - Here, we describe a fast, simple method for constructing full-length cDNA
      libraries using SMART technology. This novel procedure uses the template
      switching activity of Moloney murine leukemia virus (MMLV) reverse transcriptase
      to synthesize and anchor first-strand cDNA in one step. Following reverse
      transcription, three cycles of PCR are performed using a modified oligo(dT)
      primer and an anchor primer to enrich the cDNA population for full-length
      sequences. Starting with 1 microgram human skeletal muscle poly(A)+ RNA, a cDNA
      library was constructed that contained 3 x 10(6) independent clones with an
      average insert size of 2 kb. Sequence analysis of 172 randomly selected clones
      showed that 77% of cDNA clones corresponding to known genes contained intact open
      reading frames. The average length of complete open reading frames was 2.4 kb.
      Furthermore, 86% of the full-length clones retained longer 5' UTR sequences than
      the longest 5' end deposited in the GenBank database. cDNA libraries generated
      using this method will be useful for accelerating the collection of mRNA 5' end
      sequence information, which is currently very limited in GenBank.

PMID- 11314273
TI  - Toward a public mental health promotion and intervention system for youth.
AB  - Substantial limitations exist at all levels of mental health care for youth in
      most communities in the United States. Particular gaps exist in the areas of
      prevention, mental health promotion, and early intervention programs. The
      national movement toward enhancing mental health programs for youth in schools
      offers an important opportunity to fill gaps in the prevention-services continuum
      toward the development of a Public Mental Health Promotion and Intervention
      System for Youth. A strategy--the Child and Adolescent Program Planning Schema
      (CAPPS)--is presented to analyze gaps in a community's system of mental health
      programs for youth, and to facilitate planning toward development of a full
      continuum of programs from broad, population-based prevention, and mental health
      promotion strategies to treatment of youth with more established problems.

PMID- 11314274
TI  - Receipt of school health education and school health service among adolescent
      immigrants in Massachusetts.
AB  - This study assessed whether immigrant adolescents receive health education and
      services in schools at levels comparable to native-born peers. Surveys from 2,635
      8th and 10th graders allowed comparisons between students living in the United
      States "always" (n = 2,080), "more than six years" (n = 299), and "six years or
      less" (n = 191). Immigrant students were equally likely to receive health
      education, more likely to use peer counseling or support groups (p < .001), and
      less likely to use health services (p < .05). They communicated more often with
      staff (p < .05), were more concerned about mental health issues (p < .01), and
      were likely to have these topics addressed in school (p < .05). They were more
      positive about health education (p < .05), learned something new (p < .01), and
      communicated with parents when offered (p < .001). Schools provide a critical
      gateway and opportunity for reaching immigrant students and families with
      programs designed to meet their unique health and mental health needs. Questions
      remain, however, about health education and services being provided to non
      mainstreamed, Limited English Proficient students who recently immigrated.
      Implications for program and service delivery and future research are discussed.

PMID- 11314275
TI  - Alternative medicine: more than a harmless option.

PMID- 11314276
TI  - Traditional asthma education for adolescents.

PMID- 11314277
TI  - Five activities for student nurses at inner-city schools in Chattanooga,
      Tennessee.

PMID- 11314278
TI  - Enhancing youth achievement through telementoring.

PMID- 11314279
TI  - Virginity: a state of mind ... but not necessarily of body.

PMID- 11314280
TI  - Schoolchildren and backpacks.

PMID- 11314281
TI  - Legislation, policy, and tobacco use among youth: implications for health care
      providers.
AB  - This paper addresses implications of recent tobacco legislation, policy, and
      tobacco use among youth in the context of health care policy and services.
      Tobacco use prevalence and definitions and diagnoses of nicotine addiction and
      dependence are described. Assessment of smoking prevalence in Texas provides a
      case study of the problem and potential solutions for tobacco use among youth.
      The case study highlights specific implications to be considered when providing
      health care focused on prevention and risk reduction for youth. The paper
      concludes with implications and critical Internet resources for health care
      providers engaging in youth tobacco control.

PMID- 11314282
TI  - Autism and the school nurse.
AB  - Until recently, treatment for children with autism involved housing them in
      hospitals for the developmentally disabled. Today, more states are returning
      children with autism to their home communities, and more parents are choosing or
      are being required to keep their children with autism in their homes. Laws were
      developed to ensure that children with autism receive some form of education,
      often through the local school system. School nurses, who may not have experience
      working with children with autism, may feel uncertain about how to provide
      support for the child with autism. Approximately 300,000 persons in the United
      States have autism or display autistic behaviors. About one-third are under age
      21. People with autism come from all socioeconomic classes. Males are four times
      more likely to be affected by autism than females. People with autism can be
      expected to live a normal lifespan.

PMID- 11314283
TI  - Effects of combined aerobic and resistance training versus aerobic training alone
      in cardiac rehabilitation.
AB  - PURPOSE: This study examined the effects of performing combined resistance and
      aerobic training, versus aerobic training alone, in patients with coronary artery
      disease. METHODS: Thirty-six patients with coronary artery disease were
      randomized to either an aerobic-only training group (AE) or a combined aerobic
      and resistance training group (AE + R). Both groups performed 30 minutes of
      aerobic exercise 3 days/week for 6 months. In addition, AE + R group performed
      two sets of resistance exercise on seven different Nautilus machines after
      completion of aerobic training each day. Twenty patients (AE: n = 10; AE + R: n =
      10) completed the training protocol with > 70% attendance. RESULTS: Strength
      gains for AE + R group were greater than for AE group on six of seven resistance
      machines (P < 0.05). VO2peak increased after training for both AE and AE + R (P <
      0.01) with no difference in improvement between the groups. Resting and
      submaximal exercise heart rates and rate-pressure product were lower after
      training in the AE + R group (P < 0.01), but not in the AE group. AE + R
      increased lean mass in arm, trunk, and total body regions (P < 0.01), while AE
      increased lean mass in trunk region only (P < 0.01). Percent body fat was reduced
      for AE + R after training (P < 0.05) with a between group trend toward reduced
      body fat (P = 0.09). Lean mass gain significantly correlated with strength
      increase in five of seven resistance exercises for AE + R. CONCLUSIONS:
      Resistance training adds to the effects of aerobic training in cardiac
      rehabilitation patients by improving muscular strength, increasing lean body
      mass, and reducing body fat.

PMID- 11314284
TI  - Cardiac rehabilitation in the United Kingdom. How complete is the provision?
AB  - PURPOSE: To bring up-to-date information about all the cardiac rehabilitation
      (CR) units in the UK, including their staffing and the services they offer, and
      to determine the numbers and diagnoses of the patients they treat. METHODS:
      Questionnaire survey to establish the continued functioning of the centers, the
      disciplines of their staff, the number of patients treated, their diagnoses, and
      the outcomes measured. RESULTS: 286 centers were identified. Of the 236 who
      returned their questionnaires, 171 (72%) gave figures of the numbers and
      diagnoses of their patients. The median number treated in the different programs
      was 150, with a total of 32,499 patients. Of those, 63% were recovering from
      myocardial infarction, 25% from coronary artery bypass graft (CABG), and 4% from
      percutaneous transluminal coronary angioplasty (PTCA). Twenty-four percent of
      patients were female, 87% were between the ages of 40 and 74, and 10% were older
      than 75. Of the responders, 80 (34%) performed an exercise test both before and
      after the course. Of the 171 who gave figures, 113 (66%) measured outcomes.
      CONCLUSIONS: In the UK, between 14% and 23% of infarct patients, between 33% and
      56% of CABG patients, and between 6% and 10% of PTCA patients are enrolled into
      CR programs.

PMID- 11314285
TI  - Physical activity, physical fitness, and Framingham 10-year risk score: the cross
      cultural activity participation study.
AB  - PURPOSE: Although physical activity and physical fitness are inversely and
      causally associated with coronary heart disease (CHD) morbidity and mortality,
      available equations for estimating CHD risk do not include scores for activity or
      fitness. Therefore, this study evaluated the association of physical fitness and
      moderate-intensity physical activity with the 10-year Framingham CHD risk
      estimate. METHODS: Cross-sectional analyses were performed on data from 137
      healthy middle-aged women (53.9 +/- 9.9 yr; 28.3 +/- 6.0 kg/m2). Health
      histories, body composition, blood pressure, and blood samples were obtained from
      a clinical examination. Levels of moderate (3-6 METS) intensity physical
      activity, expressed as MET-minutes/day of energy expenditure, were derived from
      multiple 24-hour physical activity records. Physical fitness was quantified as
      duration of a symptom-limited maximal treadmill exercise test. RESULTS: After
      adjustment for race, body mass index (BMI), and hormone replacement status, a
      graded reduction in the Framingham risk score was observed across low (5.8%),
      moderate (4.0%), and high (3.6%) fitness levels (P for trend = 0.009). Women in
      both the moderate and high fitness categories had a lower (P < 0.01) risk score
      compared with their low fit counterparts. Significant differences in risk were
      not seen among low (3.9%), moderate (4.9%), and high (4.4%) physical activity
      groups. The lack of association between the risk score by physical activity may
      have been due to the homogeneity of activity levels among participants. Our
      findings reinforce existing data that show enhanced levels of fitness are
      associated with lower risk for CHD.

PMID- 11314286
TI  - Physical activity, fitness, and coronary risk estimation.

PMID- 11314287
TI  - Predictors of plasma triglyceride elevation in patients participating in a
      coronary atherosclerosis treatment program.
AB  - PURPOSE: Low-fat, high-carbohydrate diets have been used successfully to prevent
      and treat coronary heart disease, although these diets have been shown to cause
      elevations in fasting plasma triglyceride concentrations. The present study
      investigated metabolic factors (glucose, insulin, body weight) associated with
      changes in plasma triglyceride concentrations in patients participating in a
      comprehensive, multidisciplinary program, which included the use of a very low
      fat diet designed to regress atherosclerotic cardiovascular disease. METHODS:
      Thirty-six patients were entered into the study and placed on a 10% fat diet.
      Body mass index and fasting plasma insulin, glucose, lipids, and apolipoproteins
      were assessed at entrance into and after 3 months of participation in the
      program. Statistical analysis (discriminant function analysis) was used to
      identify factors that predicted elevations in plasma triglyceride that occurred
      during therapy. RESULTS: For the entire group, significant reductions in body
      weight (-2.4%), fasting glucose (-6%), total cholesterol (-8%), and low-density
      lipoprotein cholesterol (-11%) were observed, while insulin and triglycerides
      showed no significant changes. Twenty-one of the patients experienced an increase
      in fasting triglyceride concentration of 10% or greater. CONCLUSIONS: Three
      variables (baseline body mass index and fasting triglyceride and insulin
      concentrations) accurately classified 90% of those who would experience a > or =
      10% elevation in triglycerides (P = 0.0002) and 67% of those who experienced no
      change. The present analysis provides a practical algorithm for clinicians to
      predict which patients will experience significant elevations in plasma
      triglyceride concentration when undergoing risk factor reduction that includes
      the consumption of a very low-fat, high-carbohydrate diet.

PMID- 11314288
TI  - Prevalence of depressive symptoms and depression in patients with severe oxygen
      dependent chronic obstructive pulmonary disease.
AB  - PURPOSE: To measure the prevalence rate of significant depressive symptoms and
      depression and examine their consequences on quality of life in patients with
      severe oxygen-dependent chronic obstructive pulmonary disease (COPD). METHODS:
      Between November 1997 and March 1998, the authors conducted a cross-sectional
      study among the COPD patients registered at the Quebec City area respiratory home
      care service. Depression and quality of life were assessed using the Geriatric
      Depression Scale and the Medical Outcome Survey--Short Form 36 (SF-36). RESULTS:
      109 patients (63 men; mean age: 71) with severe COPD (median FEV1: 34%) were
      surveyed. Of them, 105 were on long-term oxygen therapy (LTOT), which had been
      introduced (median) 19 months earlier. Sixty-two patients (57%; 95% Cl: 47-66)
      demonstrated significant depressive symptoms; in addition, 20 patients (18%; Cl:
      12-27) were severely depressed. Only 6% of those patients who met the criteria
      for depression were taking an antidepressant drug. We found significant and
      moderate correlations between the scores obtained from the Geriatric Depression
      Scale and 7 of the 8 domains of the SF-36. CONCLUSION: Significant depressive
      symptoms and depression are highly prevalent in patients with severe COPD on
      LTOT. There is strong evidence that depression is under-recognized and under
      treated in this group of patients.

PMID- 11314289
TI  - Reference values for a multiple repetition 6-minute walk test in healthy adults
      older than 20 years.
AB  - PURPOSE: To (1) identify greatest 6-minute walk distance (6MWD) from among
      several repetitions (best 6MWD) in a wide age range of healthy volunteers to
      develop reference values for the multiple repetition 6MWD, and (2) investigate
      the influence of demographics, anthropometrics, and habitual exercise activity on
      best 6MWD. METHODS: Four 6MWD were performed on the same day in a 20-meter
      corridor by 41 male and 38 female healthy volunteers ranging in age from 20 to 80
      years. The greatest 6MWD by each subject from among four 6MWDs was the primary
      outcome measure. RESULTS: Eighty-six percent had their best 6MWD after the first
      walk; an average increase of 43 meters was observed from first to best 6MWD (P <
      0.003). Best 6MWD averaged 698 +/- 96 meters and was inversely related to age (P
      < 0.001), directly to height (P < 0.001), and was greater in men than women (P <
      0.0002). A regression model accounted for 41% of between-subject variability in
      best 6MWD (P < 0.00000001). In a subset of older subjects, predicted 6MWD
      significantly underestimated measured best 6MWD when reference values were used
      from another study where test familiarization was not provided, but this
      difference disappeared when value were used from the present and a third study
      where test familiarization was provided. CONCLUSIONS: The present study is the
      first to provide predicted 6MWD values performed with multiple repetitions and
      for subjects in the 20-40-year-old age range. Selection of appropriate predicted
      6MWD values for interpretation of performance should be guided by subject age and
      degree of test familiarization provided.

PMID- 11314290
TI  - Validating facemask use for gas exchange analysis in patients with congestive
      heart failure.
AB  - PURPOSE: Functional limitation, often associated with congestive heart failure
      (CHF), is most accurately assessed with measurement of peak VO2 (VO2peak) during
      exercise testing. VO2peak strongly predicts survival in CHF patients and is used
      to triage patients for cardiac transplantation. However, the traditional
      mouthpiece/noseclip equipment used for gas exchange analysis is often cumbersome
      and uncomfortable. Several alternative facemask designs tested previously in
      healthy cohorts were inferior to the mouthpiece for measuring VO2peak. In this
      study, a series of facemasks designed specifically for VO2peak testing (Hans
      Rudolph) was employed. Although previously validated in healthy young adults,
      this apparatus has not been validated in patients with severe CHF. METHODS: The
      Hans-Rudolph facemasks were compared with the mouthpiece apparatus in 30 patients
      with severe CHF. Each subject completed a cardiopulmonary exercise test with each
      device. Twelve subjects were randomized to evaluate a possible training effect.
      To enhance recruitment, 18 additional subjects were recruited after they had
      completed a test with the mouthpiece. RESULTS: There was no evidence of a
      training effect and no differences in gas exchange measurements were found
      between the two devices. The weight-adjusted VO2peak measurements were 17.1 +/-
      5.3 ml O2/kg/min for the mouthpiece group and 17.3 +/- 5.6 ml O2/kg/min for the
      mask group (P = 0.54). CONCLUSIONS: The facemask was shown to be equivalent to
      the mouthpiece for measuring VO2peak in CHF patients. Concerns of hypoventilation
      and decreased VO2peak associated with previous facemask designs were not
      substantiated. Since successful exercise testing depends on maximal exertion,
      providing a choice of equipment may facilitate cooperation without sacrificing
      accuracy.

PMID- 11314291
TI  - Practice transitions--past, present, and future.
AB  - Upon their retirement, dentists have gone from simply closing their office doors
      to seeing the sale of their practice as a means to fund their retirement. Today,
      other practice transition options are used to the advantage of both the retiring
      dentist and the dentist just starting out. Options will continue to meet the
      changing needs of dentists, particularly new dentists who must pay off higher
      education debts and may not opt for immediate ownership of a practice upon
      graduation.

PMID- 11314292
TI  - Ten common estate planning mistakes to avoid.
AB  - While most Americans are aware of the importance of estate planning, many fail to
      make the proper arrangements for their heirs. Problems can arise from a number of
      mistake, such as underestimating assets, relying solely on a will, or not
      planning for estate tax payments.

PMID- 11314293
TI  - Whom should I name as my IRA beneficiary?
AB  - Many times, people will end up passing on some or all of their individual
      retirement accounts to someone else. Naming a beneficiary can depend on your
      financial and family situation and should be considered carefully.

PMID- 11314294
TI  - Long-term care: a substantive factor in financial planning.
AB  - More than 50 percent of women will enter a nursing home at some point in their
      lives. About one-third of men living to age 65 will also need nursing home care.
      Planning for long-term care is even more important since Medicare covers very
      little of the cost of such care. The Indiana Partnership Plan is one program
      designed to help fund the long-term care costs while allowing individuals protect
      other financial assets.

PMID- 11314295
TI  - Embrace science!

PMID- 11314296
TI  - Staying on track with your investment plan.
AB  - The key to successful investing is not to try to pick the "hot" stocks but rather
      to invest for the long run. The best approach is not trying to predict market
      trends but making financial goals and diversifying your investments to reach
      them.

PMID- 11314297
TI  - Building a profitable practice for the future.
AB  - The success of the dental practice may be based in the skills of the dentist and
      staff, but it will take additional qualities to create the stand-out dental
      office. This practice will be dedicated to employee retention and training,
      outstanding customer service and attention from every staff member, and a focus
      on creating revenue through the best utilization of the dentist's time and staff
      experience. This successful office will also exercise cost containment and take
      advantage of marketing opportunities.

PMID- 11314298
TI  - Reporting of errors in surgery: a new trend or real patient safety issue--to err
      is human.

PMID- 11314299
TI  - CT-determined intracranial volume for a normal population.
AB  - Intracranial volume comparisons of patients with craniosynostosis and normal have
      been contrary to expectations, leading to questioning of the validity of the
      current normal reference material. Computed tomography-determined intracranial
      volume is presented for a white normal population. Specifically, intracranial
      volumes for 157 subjects (82 female and 75 male) were measured from computed
      tomography data using the Cavalieri estimator: volume determination was based on
      measuring the area in each computed tomography section. Monomolecular and
      Gompertz models were applied to find curves of best fit to the intracranial
      volume as a function of the age. The best fit was obtained using the
      monomolecular model when the response variable was the logarithmically
      transformed intracranial volume, and the independent variable was the logarithm
      of the age from conception. For example, the mean (standard deviation) for male
      subjects at 1 year and 20 years were 1,125.6 (89.6) ml and 1,472.9 (117.2) ml,
      respectively, and for female subjects 1,024.9 (84.0) ml and 1,321.7 (108.3) ml,
      respectively. Although the shape and rate of increase of the female and male
      curves is similar, the female mean is 1.3 standard deviations below the male mean
      at 20 years. These curves were compared with the commonly referenced curves of
      Blinkov (1941), Lichtenberg (1960), and Dekaban (1977). Our male curve is
      substantially higher than these curves in the age range 8 months to 4 years. Our
      female curve, however, is approximately 1 standard deviation below Lichtenberg's
      curve from birth to 7 months. There are then only minor differences between our
      female curve and Lichtenberg's curve until his curve crosses ours at 41 months,
      where they significantly diverge from approximately 4.5 years. Our curves
      indicate that 95% of the final intracranial volume has been attained by 42 months
      for girls and 46 months for boys.

PMID- 11314300
TI  - Reconstruction of complex cranial wounds with demineralized bone matrix and
      bilayer artificial skin.
AB  - Complex wounds involving loss of both cranium and scalp are difficult to
      reconstruct. Current solutions include both autogenous and alloplastic materials.
      Tissue engineering provides interesting alternatives for reconstruction of
      missing bone and soft tissue. Demineralized bone matrix and Integra, artificial
      bilayer skin substitute, have been used successfully to reconstruct bone and skin
      as isolated defects, but never in combination. This study investigates the
      possibility of using demineralized bone matrix in a gel carrier and Integra for
      combined cranial and scalp defects. The study was divided into two parts. In the
      first, demineralized bone matrix in the forms of Grafton Flex (n = 12) and
      Grafton putty (n = 12) was used to reconstruct 15-mm critical size cranial
      defects in female adult New Zealand White rabbits. In the control group (n = 6),
      the defect was left empty. The second part of the study investigated the use of
      Integra and Grafton Flex to reconstruct a 15-mm cranial defect with an overlying
      full-thickness scalp defect (n = 6). The first study revealed bony healing of the
      critical-size cranial defect with demineralized bone matrix. The second study
      demonstrated successful reconstitution of scalp and cranium with both
      demineralized bone matrix and Integra. We conclude that complex cranial defects
      involving bone and soft tissue may be successfully reconstructed with their
      tissue-engineered substrates, demineralized bone matrix (Grafton) and Integra
      artificial skin.

PMID- 11314301
TI  - A resorbable and rapid method for maxillomandibular fixation in pediatric
      mandible fractures.
AB  - Maxillomandibular immobilization in pediatric mandible fractures is accomplished
      through a resorbable screw placed into the zygomatic body to which is attached a
      large, monofilament, circummandibular suture. Although the screw must be placed
      intraoperatively, this method of jaw immobilization is rapid, secure, does not
      damage the teeth, and can be removed in the office in the older child.

PMID- 11314303
TI  - Craniofacial distraction osteogenesis en bloc.
AB  - Bone distraction of the superior and medial thirds of the craniofacial skeleton
      en bloc, avoiding a frontal craniectomy is presented. We applied this procedure
      in eight patients who were more than 5 years old with different types of
      craniofacial synostosis and who had not received previous treatment, and with a
      normal frontal shape. During monobloc advancement, major complications were
      encountered in older patients, especially the impossibility of the brain to
      expand rapidly to fill the retrofrontal dead space. Distraction osteogenesis of
      the craniofacial skeleton en bloc (without craniectomy) is feasible. Miniplates
      and screws are avoided as well as the possibility of frontal relapse or fractures
      of the frontozygomatic region. The patients did not need skull vault remodeling,
      except for a small cranioplasty at the bregma zone. The results obtained were
      satisfactory and stable at the time. This procedure avoids any kind of
      osteosynthesis, there is no extradural dead space, the operative time is brief,
      and blood loss is minimal. The inconvenience is the necessity of a second
      operation to remove the distractor.

PMID- 11314302
TI  - Biodegradable miniplates (LactoSorb): long-term results in infant minipigs and
      clinical results.
AB  - Metallic plates are known for their passive intraosseous transmission in the
      growing skull. To avoid plate removal, resorbable material with strength
      comparable to that of metallic plates and predictable resorption would be
      desirable. This should be accomplished without causing inflammatory complications
      and foreign body reactions often seen with highly crystalline poly-L-lactic acid
      or pure polyglycolic acid implants. In an animal experiment in four young
      Gottingen minipigs, the resorbable poly-L-lactic acid/polyglycolic acid copolymer
      LactoSorb was tested previously. In addition to testing the mechanical
      properties, the process of degradation and sub- versus epi- or supraperiosteal
      application of the miniplate device LactoSorb was evaluated using a frontal
      cranioosteoplasty model. Furthermore, LactoSorb was used in 10 patients with
      craniosynostosis or craniofacial trauma. During degradation, the absorbable poly
      L-lactic acid/polyglycolic acid miniplates acted like metal plates because they
      also displayed passive intraosseous transmission in the growing animal model.
      Degradation took 12 to 18 months and was not delayed by bony incorporation. Their
      mechanical properties proved to be sufficient in craniofacial surgery.
      Epiperiosteal plating prolonged the passive intraosseous transmission effect
      during the first 3 months after surgery. There were no major inflammatory
      reactions seen in the experimental and/or in the clinical study.

PMID- 11314304
TI  - Cutaneous sinus tract from remaining tooth fragment of edentulous maxilla.
AB  - Cutaneous sinus tract of dental origin usually arises from chronic dental
      infections. These tracts usually appear as suppurative lesions of the chin or
      neck. Because many patients with this lesion do not have any complaints of oral
      symptoms, these lesions are often diagnosed incorrectly and overlooked, and are
      also treated ineffectively. A case of an unusual presentation of a chronic
      suppurative granuloma on nasolabial fold, which originated from the remaining
      tooth fragment of edentulous maxilla, is reported. Treatment with removal of the
      tooth fragment as well as the sinus tract resulted in complete healing of the
      lesion. This report emphasizes the importance of awareness of the possible dental
      origin of facial sinuses, despite their unusual location.

PMID- 11314305
TI  - Temporalis muscle flap for craniofacial reconstruction after tumor resection.
AB  - Temporalis muscle flap provides a good solution for the reconstruction of
      craniofacial defects after tumor resection. Nine patients with complicated
      defects located at the upper two thirds of the face, anterior cranial base, or
      mastoid region are presented. Five patients had orbital exenteration, two with
      total maxillectomy and two with anterior craniofacial resection. Temporalis
      muscle flap provided profuse well-vascularized tissue for the obliteration of
      orbital exenteration and total maxillectomy cavities and coverage of surface
      defects. Cranial, oral, and nasal spaces were separated successfully in all
      patients. Temporalis muscle flap is a very reliable technique with low
      complication rates and few donor site problems. This safe and technically easy
      flap can be preferred for the reconstruction of craniofacial defects after
      ablative tumor surgery, especially in older and debilitated patients.

PMID- 11314306
TI  - Craniofacial traumas: immediate and delayed treatment.
AB  - In 1998, 28 patients with craniofacial fractures have been under observation at
      the Emergency Room of the Policlinico Umberto I of Rome. Twenty-six patients have
      undergone reduction and contention surgery of the fractures. The diagnosis of the
      fractures has been achieved through CT axial scanning and coronal reconstruction
      as well as with three-dimensional CT. The CT spiral was used in those cases that
      required more rapid intervention, whereas the MRI was used to evaluate the
      condition of the eyeball. Twenty of such patients underwent surgical treatment a
      few hours after the trauma and, in such cases, excellent aesthetic and functional
      results were achieved. The general and neurological conditions of six patients
      did not permit prematurely proceeding with surgery. Two patients died a few hours
      after the trauma of the injuries sustained. Of the six patients who underwent
      delayed treatment, acceptable functional and aesthetic results were achieved in
      four, whereas the remaining two patients had inadequate results. The results we
      have obtained show that it is possible to achieve the best results, both
      aesthetic and functional, through immediate treatment. Delayed treatment is
      carried out at least 2 weeks after the trauma because of the patient's condition
      and presents reconstruction difficulties that do not guarantee a satisfactory
      aesthetic reconstruction as well as, in some cases, an effective functional
      restoration.

PMID- 11314307
TI  - The spectrum of minimal clefting: process-oriented cleft management in the
      presence of an intact alveolus.
AB  - The minimal cleft lip provides a model for study of the clefting process.
      Nasolabial embryogenesis can be best understood using the concept of embryonic
      fields in which midline structures (columella, philtrum, premaxilla, septum,
      vomer, and ethmoids) develop with paired, fused A fields. Anatomic features of
      the minimal cleft lip suggest that the actual clefting site is located at the
      interface between the A and B fields within the lateral piriform wall. Study of
      the progression of clefting, using this model, places the timing of the clefting
      event to Carnegie stage 14. The degree to which this initial event affects
      subsequent fusion of the lateral and medial nasal processes (D and C fields)
      determines the final morphology of the cleft. Using this model, a rational basis
      is presented for the surgical management of minimal clefting in its varying
      manifestations.

PMID- 11314308
TI  - Re: Maxillary distraction osteogenesis: a method with skeletal anchorage.

PMID- 11314309
TI  - Effects of resistance form on attachment strength of resin-retained castings.
AB  - This study evaluated the effects of tooth preparation design on resistance to
      dislodgment of a resin-bonded fixed partial denture (RBFPD). The variations of
      tooth preparation tested included axial coverage, retentive grooves, and an
      occlusal rest. Patterns of the tooth preparation designs were prepared and cast
      in a base metal alloy. Retainer patterns were waxed to refractory casts of metal
      dies, cast, finished and then bonded to the dies. The complete assemblies were
      loaded to failure on an Instron mechanical testing machine, and analysis
      indicated that retainers with occlusal rests were the most resistant. Grooves
      provided no statistically significant increase in resistance to failure of the
      cement. Increased axial coverage did not increase resistance to dislodgment.
      Successful fixed partial dentures (FPDs) depend on cast retainers to resist
      displacement of the restoration during function. Introduction of resin-bonded
      restorations opened the possibility of FPDs with minimal reduction of abutments.
      Specific questions concerning long term success and tooth preparation designs
      were prominent concerns. The influence of resistance form on overall stability of
      a restoration was also of particular interest. Buonocore established the
      foundation for retention of composite resins to acid-pitted enamel. Rochette used
      this technology to bond perforated cast metal splints to periodontally
      compromised teeth. A mechanical interlock was created as composite resin engaged
      these perforations and sustained the cast splint to acid-etched enamel. Howe
      adapted this design for replacement of anterior teeth by adding porcelain to a
      metal ceramic framework and then bonding the framework to abutments without tooth
      preparations. The advantages of these procedures were their conservative nature,
      esthetics, and ease of rebonding after dislodgment. Livaditis and Thompson
      adapted the procedure proposed by Tanaka of corrosion-pitting the bonding surface
      of a base metal alloy. They increased the surface area to be bonded, eliminated
      the perforations to improve rigidity of the framework, and described tooth
      preparation modifications of the abutments. They suggested an occlusal rest,
      establishment of guide planes through axial reduction, and a proximal extension
      to the facial surface to resist lingual displacement. Simonson, et al., based
      their anterior tooth preparation design on the configuration suggested by
      Livaditis which included a slight chamfer finish line plus reduction of the
      lingual surface to provide a thicker metal framework. Barrack introduced an inlay
      type tooth preparation for the occlusal rest plus shallow vertical proximal
      grooves, and Meiers used grooves as an esthetic alternative to proximal
      extensions. Clinical studies and surveys have identified specific variables
      involved with success and failure, while in vitro studies have evaluated
      framework designs, bonding agents, and methods for pitting the metal surface.
      This study evaluated resistance of RBFPDs to dislodgment of different tooth
      preparation designs.

PMID- 11314310
TI  - The future: building on the past.

PMID- 11314311
TI  - Your health. The mouth is a mirror of the body.

PMID- 11314312
TI  - Dental implantology at the University of Oklahoma College of Dentistry.

PMID- 11314313
TI  - Are you doing your part to help stamp out tobacco use?

PMID- 11314314
TI  - Listening your way to case acceptance.

PMID- 11314315
TI  - Cholinsalicylate gel induced oral lesion: report of case.
AB  - Salicylic acid and its derivatives are extensively used medications for the
      treatment of systemic and local diseases. However, injudicious use of aspirin as
      well as other derivatives of salicylic acid, may cause systemic and oral
      complications such as mucosal burns and oral ulcers. In children, topical
      administration of these drugs, even in small dosages, may cause adverse
      reactions. This report shows a case of an 8 year old boy with G6PD deficiency,
      who had a mucosal burn caused by application of a cholinsalicylate paste. Three
      days later, the child developed oral ulcers, malaise and fever. The present case
      is characteristic of the enigmatic nature of the etiology and diagnosis of oral
      lesions, and the possible connection between cholinsalicylate systemic absorption
      and hemolytic anemia is discussed.

PMID- 11314316
TI  - Clinical management of traumatic bone cyst in children: a case report.
AB  - A case report of a traumatic bone cyst occurring in a 10-year-old girl which
      persisted after endodontic treatment of the teeth involved in lesion is
      presented. The importance of established clinical and radiographic diagnosis in
      order to avoid radical surgery or unnecessary endodontic treatment in children is
      discussed.

PMID- 11314317
TI  - Pediatric cervicofacial actinomycosis: a case report.
AB  - Cervicofacial actinomycosis in children is a rare disorder. This article reports
      a case in a 7-year-old-girl. The importance of cervicofacial actinomycosis in the
      differential diagnosis of cervical masses in young patients is emphasized.

PMID- 11314318
TI  - A thirty months clinical evaluation of a posterior composite resin in primary
      molars.
AB  - The purpose of this in vivo study was to evaluate the clinical performance of a
      posterior composite resin TP.H (Caulk Dentisply) in class I restorations in
      primary molars. A total of 30 children aged 5 to 8 years old with 49 class I
      dental lesions in primary molars participated in the study. The cavity
      preparations involved removal of carious lesion only and the enamel margins were
      beveled. The results showed after 30 months that, 82% (32/39) of Alfa ratings and
      18% (7/39) of Bravo ratings. We concluded that the composite resin TP-H could be
      used in conservative restorations in primary molars, particularly in the late
      mixed dentition.

PMID- 11314319
TI  - Absorbed radiation dose during lateral cephalometric radiography: comparison of
      screen-film systems and field-size combinations.
AB  - Various methods have been proposed and investigated in order to reduce radiation
      exposure in cephalometric radiography. The aim of this study was to determine the
      radiation dose absorbed by nine specific superficial anatomical regions of the
      head and neck, in children aged 9 to 17 years, by the use of three combinations
      of intensifying screens and films and different field sizes. A dental X-ray unit
      (Ortho Phos, Siemens) was used for the radiographic exposures and the absorbed
      doses were measured via thermoluminescence dosemeters. The mean doses
      corresponding to the anatomical regions in question were higher with the first
      than with the other two techniques (p < 0.05) without the thyroid gland (p >
      0.05) and in the third technique were lower than the doses of the other two
      techniques (p < 0.05) without the thyroid gland and the tip of the nose (p >
      0.05).

PMID- 11314320
TI  - Ultrasonographic and electromyographic evaluation of the labial musculature in
      children with repaired cleft lips.
AB  - Muscle thickness and activity of the labial musculature in twenty seven children
      aged 4 to 12 years, with repaired cleft lips were measured using ultrasonographic
      and electromyographic techniques respectively. The results demonstrated that the
      muscle thickness and muscle activity were more at the repaired area when compared
      to that at the normal areas, adjacent to the repaired area, on either side. No
      significant positive correlation was noted between the muscle thickness and
      muscle activity.

PMID- 11314321
TI  - Effect of chewing gum on plaque acidogenicity.
AB  - The aim of this investigation was to study the effect of chewing sucrose
      containing gum, xylitol-sorbitol-containing gum and natural gum (Pistacia
      lenticus) on the pH recovery of sucrose challenged dental plaque. Plaque pH was
      measured by microtouch electrode method on two-days old plaque. The results of
      the present study suggest that the chewing gum increases plaque pH. Chewing
      natural gum created the highest plaque pH values.

PMID- 11314322
TI  - Oral tumors in children: a review.
AB  - The objective of this study was to present an analysis of the incidence and
      diagnosis of 172 oral tumors in Jordanian children and adolescents. During the
      period of evaluation, 1605 patients with oral cavity tumors were seen. Of which
      172 (11%) were in children under 18 years, who were treated after
      histopathological confirmation of the diagnosis during the 18 years 1980-1998.
      Diagnosis, incidence and age at presentation were the main outcome measures, and
      the results showed that 156 patients (91%) had benign tumors and 16 patients (9%)
      were malignant. The most common benign tumor was haemangioma 24 (14%), and the
      most common malignant tumor was sarcoma 15 (8.5%). The most common odontogenic
      tumor was odontoma 35 (20%), and non-odontogenic tumor, ossifying fibroma 4 (2%).
      The most common site of soft tissue tumors was the lip 25 (14.5%), and of bony
      tumors the mandible 43 (25%). About 40% of the tumors developed in patients
      between the ages of 6 and 12 years. Most of the hemangiomas and lymphangiomas
      developed in patients less than 6 years old, and most of the ameloblastomas in
      those over 12 years of age. These data are important to assess geographical
      differences in the incidence of lesions and to all clinicians to make realistic
      judgments in counseling patients before biopsy about the probability of
      diagnosis. Most of these lesions were probably developmental malformations rather
      than neoplasms.

PMID- 11314323
TI  - Clear cell sarcoma of the kidney metastatic to jaw: case report.
AB  - A case of an 8 year-old boy with history of nephroblastoma (Wilms' tumor) three
      years prior, which was managed with nephrectomy, chemotherapy and radiotherapy,
      is presented. During a routine follow up, a three month old rapidly growing mass
      on the left side of the face was detected. The roentgenogram showed a lytic
      lesion in the body and ascending ramus of the left jaw. Re-evaluation of the
      previous renal tumor was interpreted as a clear cell sarcoma of the kidney.
      Biopsy of the lesion of the left jaw showed similar histology, therefore, the
      diagnosis of clear cell sarcoma of the kidney metastatic to the left jaw was
      rendered. This is a rare case and to our knowledge is the first in the world's
      literature. We emphasize the diagnostic challenge of both the primary neoplasm
      and the metastasis and discuss the differential diagnosis of primary and
      metastatic sarcomas.

PMID- 11314324
TI  - Ellis-van Creveld syndrome: dental, clinical, genetic and dermatoglyphic findings
      of a case.
AB  - Dental, clinical, genetic and dermatoglyphic findings of an additional female
      case with Ellis-van Creveld syndrome (EVC) are presented and compared with those
      of the cases cited in the literature. The dermatoglyphics of the case was
      remarkable.

PMID- 11314326
TI  - Diagnosis of HIV infection using saliva samples: comparative study between adults
      and children.
AB  - The use of saliva samples to detect the anti-HIV antibody has been described
      recently as an interesting alternative in relation to blood samples. We have
      analyzed 172 saliva samples from HIV positive and negative patients assisted at
      CASP, 108 of them adults and 64 children, in order to assess the specificity and
      sensitivity of the GACELISA test. A specificity was found of 85% and 80%
      respectively for the adult and children groups and sensitivity of 97.7% and 100%
      respectively for the adult and children groups. The statistical analysis revealed
      no differences in specificity and in sensitivity between these groups. We
      concluded that GACELISA test is useful for children.

PMID- 11314325
TI  - Salivary Streptococcus mutans, Lactobacilli levels and buffer capacity in
      children with esophageal burns.
AB  - Children with esophageal burns due to toxic ingestion are medically compromised
      in many ways. They have problems like strictures in esophagus, dysphagia,
      gastroesophageal reflux and necessity to be fed with a special soft diet. Taking
      these distinctive features into consideration, we aimed to study these children
      with special focus on the dental caries risk. The experimental group consisted of
      33 children between 2 and 14 years old (mean age 6.42 +/- 0.56) who had received
      stricture treatment in the Pediatric Surgery Department of our university. The
      control group consisted of 20 healthy children aged between 3 and 14 (mean age
      7.25 +/- 0.7) who applied to the Pedodontics department for dental treatment.
      While mean dfs (+/- SE) was 11.13 +/- 2.30 and mean DMFs (+/- SE) was 9.79 +/-
      4.76 in the experimental group, mean dfs (+/- SE) was found as 11.53 +/- 2.16 and
      mean DMFS (+/- SE) was 1.90 +/- 0.56 in control group. For the determination of
      Streptococcus mutans (SM), Lactobacilli (LB) and Buffer capacity (BC), salivary
      tests of Dentocult SM (Vivacult SM Vivadent-Liechtenstein), Dentocult LB
      (Vivacult LB-Vivadent-Liechtenstein) and Dentobuff (Vivacult BC-Vivadent
      Liechtenstein) were applied to both groups. Our findings were evaluated
      statistically and compared by the Mann Whitney Confidence Test. The amount of
      Streptococcus mutans, Lactobacilli and the level of buffering capacity in the
      children with esophageal burns showed a high caries risk. Positive correlations
      were found between SM and LB, SM and dfs, LB and dfs levels and DMFs and duration
      of stricture treatment (p < 0.05). However, negative correlations were found
      between BC and DMFs, DMFs and tooth brushing habit, dental visit and DMFs (p <
      0.05). The mean DMFs, LB and SM levels were lower and BC levels were higher in
      the control group. Although a significant difference was found between DMFs
      scores (p < 0.05), no significant difference was found between LB, BC, SM and dfs
      levels (p > 0.05). It could be concluded that children with esophageal burns have
      high dental caries risk and for this reason parental counseling about oral
      hygiene, diet, dental plaque controlling and preventive dental regimens have an
      importance in these medically compromised children.

PMID- 11314327
TI  - Removable prosthodontic treatment for the primary and mixed dentition.
AB  - Dental prosthetic treatment of children in the primary and mixed dentition years
      was planned with respect to the special conditions accompanying the absence of
      teeth. Besides the immediate functional and esthetic benefit of prosthetic
      therapy, the prosthetic appliance helps to maintain the oral functional status,
      which is considered necessary for undisturbed lower facial growth. Therefore,
      careful follow-up and thoughtful treatment decisions should be exercised,
      especially in cases where impairment of permanent dentition and supportive
      tissues complicate the prognosis.

PMID- 11314328
TI  - The use of pre-implantation tooth lengths in the treatment of avulsed teeth.
AB  - This study examines the significant difference between clinical and radiographic
      root lengths taken using paralleling technique at various degrees of angulation.
      Seventeen extracted maxillary central incisors were measured and compared to
      clinical and radiographic root lengths obtained by using paralleling technique at
      various angulations. This result supports the importance of measuring the actual
      root lengths of the avulsed teeth before re-implantation, in order to improve the
      success rate of the endodontic management phase.

PMID- 11314329
TI  - Children with baby bottle tooth decay treated under general anesthesia or
      sedation: behavior in a follow-up visit.
AB  - The purpose of the present study was to compare the behaviors of a group of
      children, who were treated for baby bottle tooth decay (BBTD) under general
      anesthesia (GA) or under sedation in a dental school environment in a routine
      follow-up examination, and to assess the dental anxiety levels of the parents.
      Sixty-five children, who were treated for BBTD in the Pediatric Dentistry clinic
      of the Hebrew University-Hadassah School of Dental Medicine between 1995-1997
      under GA (34 children) or sedation (31 children). The parents of these children
      agreed to attend our clinic for recall examination 13 months post treatment
      following a telephone conversation. Frankl's behavioral scale and the sitting
      pattern were recorded for each child. In the sedation group, Frankl's scores of
      the present visits were then compared to the scores recorded at the initial
      examination visit that were obtained from the dental records. The accompanying
      parents were asked to note the number of visits to the dentist in the past two
      years, and to complete Corah's dental anxiety scale (DAS). No difference was
      observed between the children in both groups. Most of the children in the GA and
      in the sedation groups sat alone on the dental chair, without the assistance of
      the parents. Parents of the sedation group showed higher scores than the GA group
      in the total DAS (9.35 and 8.90 respectively), however these differences were not
      statistically significant. It is concluded that children treated for BBTD under
      GA or under sedation at a very young age behave similarly in a follow-up
      examination nearly 13 months postoperatively.

PMID- 11314330
TI  - Banded block.

PMID- 11314331
TI  - Second molar removal: how this treatment fits into my practice.

PMID- 11314332
TI  - Second molar extraction: a personal odyssey comes to logical fruition.

PMID- 11314333
TI  - Second molar extraction technique: overrated or underutilized?

PMID- 11314334
TI  - Changes in genioglossus muscle activity in obstructive sleep apnea patients with
      and without snore guard.
AB  - OBJECTIVE: To study the effect of Snore Guard on the genioglossus (GG) muscle
      activity of obstructive sleep apnea (OSA) patients. MATERIALS AND METHODS:
      Fifteen male patients with mild to severe OSA were diagnosed by overnight
      polysomnographic studies, and were reexamined after using Snore Guard for 2-6
      months. The difference in GG muscle activity was then compared. RESULTS: The
      overnight GG muscle activity decreased significantly with Snore Guard. The levels
      of GG muscle activity during awake quiet breath and obstructive sleep apnea were
      higher than in sleepstate quiet breath without Snore Guard, and significantly
      decreased with Snore Guard. The increase in GG muscle activity during sleepstate
      quiet breath with Snore Guard was not statistically significant. The fluctuating
      GG muscle activity without Snore Guard was effectively improved by treatment with
      the appliance. CONCLUSION: The effect of Snore Guard on OSA patients is a
      mechanical enlargement of upper airway volume. The genioglossus muscle is passive
      during treatment.

PMID- 11314335
TI  - Changes of transforming growth factor beta 1 in rat periodontal tissue during
      orthodontic tooth movement.
AB  - OBJECTIVE: To investigate the distribution and change of transforming growth
      factor beta 1 (TGF-beta 1) in rat periodontal tissue and understand the role of
      TGF-beta 1 in orthodontic tooth movement. METHODS: Force was applied on right
      maxillary first molars in rats, followed by the examination of the decalcified
      alveolodental connected tissue in different stages of tooth movement. An
      immunohistochemical staining technique (SP method) was used for this examination.
      RESULTS: TGF-beta 1 exists in normal periodontal tissue. The expression of it in
      periodontium increases during orthodontic tooth movement. From 5 to 10 days after
      applying force, the expression at the tension site was significantly greater than
      that at the pressure site. CONCLUSIONS: Changes in TGF-beta 1 levels play an
      important role in the remodeling of periodontal tissue during orthodontic tooth
      movement, and can powerfully promote bone formation.

PMID- 11314336
TI  - P-glycoprotein expression in squamous cell carcinoma of the oral and
      maxillofacial region.
AB  - OBJECTIVE: To investigate the mechanism of drug resistance in oral and
      maxillofacial carcinoma to chemotherapy. MATERIALS AND METHODS: Forty cases of
      squamous carcinoma in the oral and maxillofacial region were examined for the
      multidrug resistance gene product P-glycoprotein using a monoclonal antibody,
      MRK16. RESULT: P-glycoprotein was detected in 62.5% of all samples. P
      glycoprotein expression was related to the chemotherapy and the differentiation
      of carcinoma. P-glycoprotein expression was higher in the post-chemotherapy group
      than in the non-chemotherapy group (P < 0.05). Well-differentiated tumors
      expressed P-glycoprotein more frequently (P < 0.05). P-glycoprotein expression
      was compared with clinical response to chemotherapy. The accuracy rate of
      prediction was 75%. CONCLUSION: P-glycoprotein plays an important role in
      mechanism of drug resistance of squamous cell carcinoma in the oral and
      maxillofacial region.

PMID- 11314337
TI  - Experimental study of phosphopeptide in promoting tooth remineralization.
AB  - OBJECTIVE: To explore a new method for effective and safe prevention and
      treatment of caries. METHODS: Following the theory of tooth remineralization, we
      searched for the mechanism and clinical application of tooth remineralization
      with phosphopeptide. RESULTS: Phosphopeptide, with calcium and phosphorus, had a
      high affinity for hydroxyapatite and could enhance tooth remineralization.
      CONCLUSION: Phosphopeptide was effective in the prevention and treatment of tooth
      decay. Clinically, it could be safely applied.

PMID- 11314339
TI  - Analysis of the mandibular position in malocclusion patients.
AB  - OBJECTIVE: To study the changes of condyle position and occlusion between centric
      jaw relation (CR) and maximum intercuspation (MI) positions. METHODS: The power
      centric registration advocated by Roth was used to take centric relation bite
      registration for 50 patients (25 Angle Class I, and 25 Angle Class II).
      Diagnostic models were mounted and analyzed with Panadent articulator and
      condylar position indicator. RESULTS: Nearly all patients had CR-MI difference in
      all three spatial planes. Seventy percent of the sagittal displacement was within
      2.0 mm and 87% of the transverse displacement was within 1.0 mm. Movement of most
      of the condyles was posterior and inferior. Sixty-five percent of the initial
      contacts in CR occurred on the most posterior molar on one side. When the
      mandible moved from CR to MI, overbite deepened, overjet decreased, and molar
      relationship became mesialized. Correlation was found between some variables of
      condylar displacement and occlusion changes. No significant difference between
      Angle Class I and Angle Class II patients was observed in condylar position and
      occlusion changes. CONCLUSION: The occlusion in centric jaw relation should be
      analyzed before treatment to reveal the disharmony between occlusion and jaw
      position.

PMID- 11314338
TI  - Fusion of low-fusing porcelain to Ti-75 alloy: an experimental study.
AB  - OBJECTIVE: To study the stomatological feasibility of low-fusing porcelain fused
      to Ti-75 alloy. METHODS: Electroprobemicroanalysis (EPMA) and shear test were
      used to observe interface state and bonding strength of porcelaintitanium.
      RESULTS: Shear bond strengths of low-fusing porcelain with Ti-75 alloy and
      conventional porcelain each fused to metal (NC-VMK68) were 47.38 +/- 7.95 MPa and
      48.50 +/- 7.60 MPa, respectively. There was no significant difference between the
      shear bonding strength of low-fusing porcelain with Ti-75 and that of
      conventional porcelain fused to metal (PFM) (P > 0.05). EPMA showed that Ti-75
      alloy and low-fusing porcelain bound tightly, had no fissure, and that low-fusing
      porcelain had good infiltration to Ti-75. It was shown that Ti spread from Ti-75
      basal body into porcelain, and elements such as Si-Sn spread from porcelain to Ti
      75. CONCLUSION: Ti-75 alloy can be used stomatologically, as a porcelain alloy.

PMID- 11314340
TI  - Assessment of trigeminal somatosensory evoked potentials in burning mouth
      syndrome.
AB  - OBJECTIVE: The measurement of pain threshold (PT) and the assessment of
      trigeminal somatosensory evoked potentials (TSEPs) were performed. These
      experiments indicated the pathological conditions of nerve afferent and efferent
      pathways in patients with burning mouth syndrome (BMS). This study also explored
      the probable pathophysiological mechanisms in BMS. MATERIALS AND METHODS: The
      dorsum linguae of 38 samples in 19 subjects (22 BMS with pain, 10 BMS with
      numbness, and 6 controls) were stimulated by electroneuromyography. PT was
      measured as the lowest stimulation intensity the subjects could detect. N3, P4
      latency, and spike potential latency of TSEP were recorded by stimulating the
      lingual nerve. RESULTS: Pain thresholds were significantly lower, N3, P4
      latencies were significantly shorter, and the spike potential appeared earlier in
      the BMS with pain group (P < 0.01). The opposite tendency of these values
      presented in the BMS with numbness group (P > 0.05). CONCLUSIONS: The results
      indicated that the nerve sensitivity was elevated in the BMS with pain group, and
      that these patients were easily affected by etiological factors. In the BMS with
      numbness group, partial or complete nerve blockage may have been indicated. This
      study suggested that selfreports of BMS pain appeared to be of value, and that
      there were pathological conditions in nerve transmission. It supported the theory
      that peripheral or central nervous system involvement might play an important
      role in BMS. It was possible to show the pathogenesis of BMS. All of these
      objectively explain the clinical understanding of BMS, and may be of assistance
      in the treatment of BMS.

PMID- 11314341
TI  - Eosinophilic ulcer of the oral mucosa: a clinicopathological analysis.
AB  - OBJECTIVE: To explore the clinical characteristics, histologic features, method
      of treatment, and possible etiology of eosinophilic ulcer of the oral mucosa.
      METHOD: Eight cases of eosinophilic ulcer of the oral mucosa were analyzed.
      RESULTS: In all cases, the ulcer site was the tongue. Ulcers were unifocal, had a
      benign course, and three of patients had a history of EUOM recurrence.
      Pathological features showed an extensive inflammatory cell infiltration, with
      predominantly eosinophilic cells throughout the submucosa. All ulcers were
      treated with either conservative excision or incisional biopsy. CONCLUSIONS:
      Eosinophilic ulcer is a rare, self-limiting benign disease that often appears in
      older adults or children. Its etiology remains obscure and may be associated with
      traumatic factors. This study provides useful information on clinical and
      pathological features, diagnosis, treatment, and prognosis, as well as the
      possible etiology of this disease.

PMID- 11314342
TI  - Expression of amelogenins in developing embryonic and neonatal rat teeth.
AB  - OBJECTIVE: Tooth enamel is formed by ameloblasts, which are derived from
      epitheliums and secrete an extracellular matrix containing a complex arrangement
      of protein components. The epithelial component, referred to as the enamel organ,
      contains a layer of cells that secrete an organic matrix that biomineralizes to
      become tooth enamel. Adjacent ectomesenchyme cells differentiate to become
      dentinproducing odontoblasts. These two mineralized matrices form the crown of
      the vertebrate tooth. Therefore, amelogenins play a critical role in tooth enamel
      formation. We have examined the expression patterns and tissue distribution of
      amelogenins in their developmental stages in order to build a foundation for
      further study. METHODS: Amelogenin expression patterns and tissue distribution in
      developing teeth of embryonic (E17E19) and neonatal (1 to 9 days old) Wistar rats
      were examined by immunohistochemistry. RESULTS: Positive immunostaining for
      amelogenin was first observed in the late embryonic stage, E18. The highest level
      of amelogenin was noted in neonatal secretary ameloblasts, fully engaged in
      enamel matrix deposition (3 to 5 days old). After that, amelogenin expression
      continued at a lower level (6, 7, 8 days old). There was no amelogenin staining
      observed in the maturation stage of development (9 days old). CONCLUSIONS:
      Amelogenin expression occurs as early as the polarization stage of pre
      ameloblasts. Amelogenin was also expressed, but at a low level, in post-secretary
      stages of amelogenesis. Odontoblasts did not contain detectable amelogenin.

PMID- 11314343
TI  - Actions of bovine plasma fibronectin on cultured human dental pulp cells.
AB  - OBJECTIVE: Fibronectin (FN) has been shown to play a crucial role in odontoblast
      differentiation, and it is involved in the repair of dentine and pulp. The
      responsiveness of human dental pulp (HDP) cells to bovine plasma FN was
      investigated. MATERIALS AND METHODS: After isolation and selection noncarious
      freshly extracted third molars in vitro, HDP cells were incubated for 72 hours
      one of four concentrations (10, 20, 40, 80 micrograms/ml) of bovine plasma FN
      with Dulbecco's modified eagle medium (DMEM) containing 1% fetal calf serum
      (FCS). We examined cell proliferation (using an MTT assay), DNA synthesis (using
      incorporation of [3H]-thymidine), the cell area, and alkaline phosphatase
      (ALPase) activity of the culture supernatant. The expression of FN, types I and
      III collagens, binding of lectins concanavalin(ConA), or wheat germ agglutinin
      (WGA) in vitro was examined by means of immunocytochemistry. The expression
      degree and the cell area were analyzed semi-quantitatively with an image
      processing and analysis system. RESULTS: After 72 hours, HDP cells appeared
      contracted and smaller in the absence of FN when compared to cells incubated with
      FN. HDP cells were in spread state with all four concentrations of FN. FN (20, 40
      micrograms/ml) stimulated cell proliferation, promoted incorporation of [3H]
      thymidine, and increased the levels of ALPase activity in supernatant. The
      binding of ConA, the expression of type I collagen, and FN were significantly
      increased, while the binding of WGA, and the expression of type III collagen were
      significantly decreased in the FN (40, 80 micrograms/ml) groups when compared to
      the FN (10, 20 micrograms/ml) groups. CONCLUSION: These findings suggest that HDP
      cells utilize FN for attachment and subsequent spreading. FN might have mitogenic
      activity and some role in the regulation of differentiation of pulp cells into
      odontoblasts.

PMID- 11314344
TI  - Detection of interleukin-8 in exudates from normal and inflamed human dental pulp
      tissues.
AB  - OBJECTIVE: The purpose of this study was to investigate the level of IL-8 in
      exudates clinically obtained from normal and inflamed human dental pulp tissues
      so as to reveal the possible relationship between IL-8 and pulpitis. METHODS:
      Samples of 2 microliters of pulpal exudate from each normal or clinically
      diagnosed as acute or chronic pulpitis teeth was obtained by filter paper strips
      and IL-8 level was measured by ELISA method. RESULTS: No IL-8 was detected in the
      samples from normal pulp, but significant amount of IL-8 appeared in inflamed
      pulp tissues, and the level of IL-8 in exudates of acute stage of pulpitis was
      higher than that of chronic stage (P < 0.01). CONCLUSIONS: This study
      demonstrates that IL-8 is produced and accumulated in pulp inflammation and may
      play a role in the occurrence and development of human pulpitis.

PMID- 11314345
TI  - The expression kinetics of myogenin in facial muscle denervation.
AB  - OBJECTIVE: To study the expression kinetics of myogenin in long-term denervated
      facial muscle and to explore the possibility of gene therapy for facial muscle
      paralysis with myogenin gene. MATERIALS AND METHODS: In 48 New Zealand rabbits,
      buccal muscle paralysis of one side was produced by excision of 1 cm segment
      buccal branch of the facial nerve. The opposite side served as controls. The
      animals were sacrificed and the buccal muscles of both sides were removed for
      examination at 1 day, 3 days, 1 week, 2 weeks, 1 month, 2 months, 4 months, and 6
      months after the initial operation. The myogenin expression in denervated and
      innervated buccal muscles was analyzed by Western blot. Satellite cell
      proliferation was detected with proliferating cell nuclear antigen (PCNA)
      analysis. Muscle nucleic acid concentration was determined through acridine
      orange (AO) staining method. RESULTS: Myogenin expression increased to the
      highest level at 3 days after denervation, thereafter it gradually decreased. The
      Western blotting signal for myogenin intensified again after 1 month and at 4
      months. In contrast, the highest expression of the controls (innervated muscles)
      were observed at 1 month. These changes in myogenin expression in denervated
      buccal muscles were consistent with the change in satellite cell proliferation
      and in muscle nucleic acid concentration. CONCLUSION: Myogenin protein expression
      in longterm facial muscle denervation is closely associated with satellite cell
      regeneration. Myogenin may promote satellite cell differentiation, and therefore
      may improve the treatment of facial paralysis.

PMID- 11314346
TI  - Child behavior in a private pediatric dental practice associated with types of
      visits, age and socio-economic factors.
AB  - The purpose of this study was to describe child patient behavior patterns seen in
      a private pediatric dental practice. Patient behavior for every individual visit
      was recorded over a span of 3 consecutive months using the Sarnat Behavior Scale
      as the descriptive measurement device. Behavior during 5 categories of procedures
      was recorded: new patient examination/introduction to the office, periodic
      recare, restorative dentistry, orthodontic adjustment and quick check
      observation. Socio-demographic variables such as age, sex, method of payment as
      an indicator of socio-economic status, prior dental experience and referral
      source were also recorded. The results of this study showed: 1. the younger the
      child and the more threatening the procedure, the more often negative behavior
      was noted, 2. patients whose dental treatment was paid for by Medicaid and who
      are likely to be in a lower socio-economic strata, often exhibited more negative
      behavior than the fee-for service counterparts, 3. in general, there was no
      difference in the behavior between males and females, although males age 8 to 12
      had a higher incidence of negative behavior than females when undergoing
      restorative dental procedures. There are trends between age, type of procedure,
      source of patient referral, method of payment and familiarity with the office,
      that may be able to used as behavioral predictors in a private pediatric dental
      office.

PMID- 11314347
TI  - Labiolingual and mesiodistal positioning of maxillary permanent incisors during
      the eruption process.
AB  - This study aimed to establish radiographical parameters concerning the tipping,
      the labiolingual positioning and the angulation of the maxillary permanent
      incisors in the mixed dentition. Three groups of 20 cephalograms and 20
      orthopantomographic radiographs taken from children aging from 7 to 12 years old,
      with normal occlusion were compared. The Group I presented only the eruption of
      the central permanent incisors, the Group II presented both the central and
      lateral permanent incisors and the Group III presented central, lateral incisors
      and permanent canine teeth. The tipping and the labiolingual positioning were
      measured, respectively, using U1/PP and U1<-->AVERT. Mesiodistally, the angles
      between the teeth axis and the line that touched the lower border of the orbit in
      the orthopantomographic radiographs were measured. The mean values of tipping,
      labiolingual positioning and angulation of the central and lateral incisors
      obtained from Groups I, II and III were respectively 112 degrees, 1.2 mm, 90.4
      degrees and 91.7 degrees; 112 degrees, 2.6 mm, 89.5 degrees and 96.8 degrees and
      114 degrees, 2.7 mm, 87.4 degrees and 92.6 degrees. The tipping levels were
      similar for all groups, the mean values of the labiolingual positioning were
      significantly different at 5% when Group I was compared to both Groups II and
      III. And the mean values of the angulation were significantly different 5% for
      the central incisors between Groups I and III, and at 1% for the lateral incisors
      between Groups I and II, and, II and III.

PMID- 11314348
TI  - Cephalometric studies of children with long and short faces.
AB  - The purpose of this study was to investigate the facial morphologic
      characteristics in children with long and short faces. Lateral cephalometric
      radiographs of 46 children with long faces and 42 children with short faces were
      used. Both boys and girls with long faces exhibited upright incisors, excessive
      upper dentoalveolar development, shorter posterior face height, shorter ramus
      height and mandibular body, greater gonial angle and backward rotation of
      mandible when compared with those with short faces.

PMID- 11314349
TI  - Microabrasion of teeth with discoloration resembling hypomaturation enamel
      defects: four-year follow up.
AB  - Microabrasion with 18% HCl and pumice to remove enamel dysmineralization and
      improve esthetics is an accepted and effective treatment. This technique can
      probably be extended even to generalized defects resembling hypomaturation
      amelogenesis imperfecta that appear on all erupted teeth. Five children aged 9 to
      11 with two types of enamel-hypomaturation probably due to developmental defects
      were treated successfully by microabrasion, with marked improvement of the
      discoloration. The patients were followed for up to four years. During this
      period, no tooth-sensitivity or staining was noted. The teeth looked healthier
      and shinier.

PMID- 11314350
TI  - Avulsion of posterior primary teeth and space maintaining appliance: case report.
AB  - A four-year-old child was presented to the Pediatric Dentistry Clinic of the
      Federal University, 21 days after an incident in which canine first and second
      primary molar teeth were avulsed, due to a trauma to the face. This was confirmed
      on radiological examination. The clinical examinations showed that tissues were
      normal. A removable space-maintaining dental-mucosa supported appliance was made
      in acrylic resin to replace the three missing teeth. After a period of eight
      months, the tissues were preserved, the device is helping the child to eat, to
      speak, and preserving the appearance of the patient. Radiograph examinations have
      shown that the first molar tooth and canine, first pre molar and second pre molar
      teeth are erupting normally. Trauma in primary dentition can cause psychological,
      morphological and functional problems. In the presented case the treatment was
      planned to recuperate the function and to avoid problems from the premature loss
      of primary teeth.

PMID- 11314351
TI  - Hereditary gingival fibromatosis: report of three cases.
AB  - Three cases of generalized and severe HGF in young patients of the same family
      without other features are reported. The purpose of this article is to present
      documented cases and discuss the identification, treatment, and control of the
      disease. The histopathological characteristics of HGF are emphasized.

PMID- 11314352
TI  - Histopathology of the pulp of primary molars with active and arrested dentinal
      caries.
AB  - The purpose of this study was to compare the histological appearance of the pulp
      of human primary molars with active and arrested lesions. The sample consisted of
      36 primary molars (18 with active lesions and 18 with arrested lesions) extracted
      from 35 children between 5 to 9 years of age. The histological diagnosis was
      classified in normal pulp, transitional stage, partial pulpitis, total pulpitis
      and total necrosis, and then subdivided in three subgroups: treatable,
      untreatable and questionable. Results showed that normal pulp or transitional
      stage (treatable category) was diagnosed in 50% of teeth with arrested lesions,
      compared to 11.1% of teeth with active lesions. Partial pulpitis (questionable
      category) was present in 38.8% with arrested lesions compared to 22.2% with
      active lesions. Total pulpitis and total necrosis (untreatable category) was
      diagnosed in 11.2% with arrested lesions compared to 66.7% with active lesions.
      The observed frequencies of histological categories between both groups were
      statistically significant (P < 0.05). Histologically, pulp reaction under active
      and arrested lesions in primary molars revealed the formation of a basophilic
      calcio-traumatic line at the junction of the primary and reparative dentin,
      formation of reparative dentin and a regular odontoblastic layer in 60% of the
      cases. Results indicated that the type of lesion (active or arrested) is a good
      indicator of the histological status of the pulp.

PMID- 11314353
TI  - Management of wide open apices in non-vital permanent teeth with Ca(OH)2 paste.
AB  - A retrospective study on 15 non-vital immature incisor teeth was done using
      Ca(OH)2 Pulpdent paste. A success rate of 100 percent was achieved within one
      year. The variables influencing the time taken for apexification were also
      evaluated. The teeth were followed up to a period of 24 months. It was found that
      older children having narrow open apex had a shorter treatment time than the
      younger children (NS); teeth without periapical infection showed some amount of
      root growth and closing of apex that was faster than those with periapical
      infection (p < 0.001). The calcified bridge formed following apexification is a
      porous structure. This investigation provides information about the time taken
      and procedure required to achieve apical barrier formation in non-vital immature
      incisors.

PMID- 11314354
TI  - The effect of caries detector dyes and a cavity cleansing agent on composite
      resin bonding to enamel and dentin.
AB  - This study was undertaken to evaluate the effect of caries detector dyes and/or
      cavity cleanser on composite bonding and etching patterns of enamel and dentin.
      One hundred and eight non-carious premolars were divided into six groups
      according to the enamel and dentin pretreatment investigated. The different
      pretreatment were as follows: Group I: teeth with prophylaxis only, Group II:
      Sable seek caries detector dye, Groups III: chlorhexidine cavity cleanser, Group
      IV: the caries detectors dye followed by prophylaxis, Group V: the cavity
      cleanser followed by the caries detector dye, and Group IV: Snoop caries detector
      dye. The shear bond strength of composite resin bonded to enamel and dentin was
      evaluated by the Instron Universal testing machine while, the topographic details
      of enamel and dentin were examined by the SEM following the different
      pretreatment and acid etching. Results of the shear bond strength showed no
      statistically significant difference among the six groups, with no substantial
      differences in SEM results. It is concluded that using the caries detector dyes
      and/or chlorhexidine cavity cleanser before acid etching does not significantly
      affect composite bonding to enamel and dentin.

PMID- 11314356
TI  - Pulpal evaluation of two adhesive systems in rat teeth.
AB  - Formocresol is the agent most frequently used with pulpotomies in primary teeth,
      but its use is currently under discussion in regard to its possible toxic
      effects. Some current works suggest the use of dentinal adhesives in cavities
      with minimal dentinal thickness and even in small pulpal exposures. Our objective
      was to evaluate pulpal response to the application of two dentinal adhesives
      Syntac and Prime & Bond NT in pulpal exposures in rat teeth. Sprague Dawley rats
      were used, male, 150 to 200 gm in weight. The maxillary first molar, left and
      right, was employed in each case, a total of twelve teeth. Duration of the study
      was 45 days. Sections were evaluated using a light microscope in order to
      determine pulpal response to the two adhesives. In both groups the persistence of
      chronic inflammation was associated with the absence of dentinal bridges in the
      affected specimens. Areas of necrosis and absence of regularity of the
      odontoblastic layer could also be seen.

PMID- 11314355
TI  - Short term human primary pulpal response after direct pulp capping with fourth
      generation dentin adhesives.
AB  - The purpose of this study was to evaluate the effects of the total-etch and
      direct pulp capping techniques on the short-term response of mechanically exposed
      human primary tooth pulps using three commercially available adhesive resin
      systems. Class V cavities were prepared on the buccal surface of intact
      mandibular primary molars and exposed with a carbide bur on the cavity floor. The
      entire cavity except the exposure site received 36% phosphoric acid gel
      conditioning. Exposed pulps were capped with one of the three adhesive resins,
      followed by restoration of the cavities with the respective restorative
      materials. The teeth were extracted after 60 days and prepared according to
      normal histological techniques. Serial sections were stained with H/B for
      histological evaluations. The histopathological evaluation showed that a few of
      the samples in the Scotchbond Multi Purpose (SMP) and Prime & Bond 2.1 (PB)
      groups exhibited "attempted bridge formation", while no bridge formation was
      evident in the other samples. Syntac Single Component (Syntac) exhibited the most
      severe histological response, while the mildest reactions were observed in the
      SMIP group. Based on the conditions of the present study, direct pulp capping
      with dentin bonding agents following the total-etch technique in primary teeth
      can not be recommended.

PMID- 11314357
TI  - Oral conditions in children from birth to 5 years: the findings of a children's
      dental program.
AB  - The study aimed to assess oral conditions other than caries and gingival
      inflammation present in the mouth of children from birth to 5 years old attending
      a Community Dental Program. Data were collected through the examination of all
      dental records, who attended the clinic from November 1997 until November 1999. A
      total of 1042 records were examined. The results showed that 97.7% of the
      patients had no lesions present in the mouth during the visits to the clinic,
      while 2.3% who presented did have lesions. The conditions most frequently found
      were: Bohn's nodules, candidiasis and benign migratory glossitis.

PMID- 11314358
TI  - Neurinoma in the buccal mucosa.
AB  - A 14-year-old girl was referred to our clinic with a problem of a painless slow
      growing lesion for approximately three years. MR imaging findings of lesion was
      "retention cyst of the salivary gland". Controversially, the histological
      examination of the total excised specimen was "neurinoma" and that was
      inconsistent with MR findings. Neural tissue tumors of the oral cavity are rare,
      however, this diagnosis was confirmed by surgical excision and histopathological
      examination. There was a rare location of the lesion as well.

PMID- 11314359
TI  - Rhabdomyosarcoma in children: report of two cases.
AB  - Rhabdomyosarcoma of soft tissue is the commonest sarcoma in pediatric medicine
      and comprises 15% of the solid tumors treated in pediatric oncology. It has an
      ample variety of clinical presentations in diverse organs and also presents a
      gamut of histopathological patterns, which sometimes make diagnosis difficult. We
      report two cases of rhabdomyosarcoma: one of the embryonic histological variety
      and the second one of the alveolar variety, which presented themselves in the
      preauricular and masseteric areas respectively. Both patients were male,
      diagnosed and treated.

PMID- 11314360
TI  - Evaluation of audio analgesia for restorative care in children treated using
      electronic dental anesthesia.
AB  - The purpose of this study was to evaluate the effectiveness of music and white
      noise in the management of sensitive children treated using electronic dental
      anesthesia for restorative care. Sound (music and random noise) was used in
      combination with electronic dental anesthesia in 16 pediatric patients, who have
      been found to have low pain tolerances during operative procedures under
      electronic anesthesia alone. Pain was assessed by means of two scales, the color
      scale and the sound, eye and motor scale. Behavior was assessed through use of
      the North Carolina Behavior Rating Scale. The comfort was evaluated mainly during
      penetration of the dentin-enamel junction of the tooth. A procedure involving
      music and "noisy" music has been effective in 14 children. The music promoted
      relaxation, whereas the "noise" in combination with electronic signals suppressed
      pain. It has been demonstrated that audio analgesia and electronic dental
      anesthesia are quite compatible and may be used with considerable success in
      combination in difficult circumstances.

PMID- 11314361
TI  - Increased susceptibility to gingival colonization by specific HACEK microbes in
      children with congenital heart disease.
AB  - It is well established that infective endocarditis (IE) involving the HACEK
      (Hemophilus, Actinobacillus, Cardiobacter, Eikenella, Kingella) group of microbes
      occurs in patients with congenital heart defects (CHD) and in those with
      prosthetic grafts. Dental caries and gingival disease have been presumed to be
      the focus of microbial shedding. The purpose of this study was to determine if
      children with CHD had a more severe gingival inflammatory condition and harbored
      the HACEK group of microbes to a greater extent than normal children. Two groups
      of 12 age and sex matched children were selected for this study. The experimental
      group consisted of twelve children with CHD, 1-1/2 to 8 years of age. The control
      group consisted of 12 healthy children 2 to 8 years of age. Each child had a
      gingival index score recorded as described by Massler. Subgingival cultures were
      obtained. Gingival samples were cultured for HACEK microbes and total
      Streptococcus (spp) using standard techniques. Fisher's exact test was performed
      with significance defined at P < 0.05. Children with CHD had more severe gingival
      inflammatory index than the control group (P < 0.05). 8/12 CHD patient had
      Actinobacillus actinomycetemcomitans (A.a.) as compared with 2/12 controls (P <
      0.05). Furthermore, all cyanotic CHD patients (4/4) had A.a. whereas, only 2/12
      controls did (P < 0.05). 4/12 CHD patients harbored Eikenella corrodens (E.c.)
      compared to 1/12 controls (N.S.). There was no significant difference in
      colonization with E.c. or A.a. between cyanotic and acyanotic patients. No
      significant difference in total Streptococcus (spp) was found between the two
      groups. This study suggests that children with CHD have a more severe gingival
      inflammatory index and are colonized with specific HACEK microbes more so than
      normal children.

PMID- 11314362
TI  - To each his own.

PMID- 11314363
TI  - Mandibular molar distalization with the Franzulum Appliance.

PMID- 11314364
TI  - Accuracy of a computerized method of predicting soft-tissue changes from
      orthognathic surgery.

PMID- 11314365
TI  - The modified Bluegrass appliance.

PMID- 11314366
TI  - Eruption of impacted canines with an Australian helical archwire.

PMID- 11314367
TI  - A new polishing system for enhanced esthetics after debonding.

PMID- 11314368
TI  - Management & marketing. Are the fees right?

PMID- 11314369
TI  - Lingual segmented treatment in the maxillary arch.

PMID- 11314370
TI  - Bonding the gap between petralit and ceromers: with case reviews.
AB  - The search for a metal-free, aesthetic restoration with optimal strength,
      longevity, and comfort easily dates back to the 19th century. However, the
      popularity of adhesively retained restorations has reached an all-time high due
      to improvements in wear, post-op sensitivity, bond material and strength, and
      aesthetic quality. Targis/Vectris, a ceromer restorative material introduced in
      1997 by Ivoclar-Williams, is a ceramic optimized polymer that produces a strong
      fiber-reinforced tooth-colored restoration. It allows the clinician to fabricate
      metal-free restorations without the fracture potential seen with ceramic
      materials. Long-term longitudinal studies of this restorative material will be
      the litmus test, but we now have 10-year studies that show very promising
      results.

PMID- 11314371
TI  - Assessing ethics and professionalism in dental education.
AB  - The foundation for the development of ethical sensitivity and the capacity for
      reflective reasoning about ethical dilemmas must be established early during
      professional training. At Indiana University School of Dentistry, two assessment
      tools, the Dental Ethical Sensitivity Test (DEST) and the Defining Issues Test
      (DIT) are being employed to help measure student achievement and enhance their
      skills in this area. Evidence suggests that both small-group discussion and case
      based problem solving involving ethical issues improve scores on these measures.
      It is imperative that opportunities to recognize, analyze, and discuss ethical
      issues are integrated throughout the dental student's educational program.

PMID- 11314372
TI  - Looking at the importance of public relations.

PMID- 11314373
TI  - Evidence-based care: a new formula for an old problem?

PMID- 11314374
TI  - Patient selection for dental implants. Part 1: data gathering and diagnosis.
AB  - In today's dentistry, dental implants have become an excellent choice of
      treatment for multiple situations. The prognosis of this treatment modality, like
      any other in dentistry, is highly dependent on appropriate case selection. A
      multi-stepped data-gathering process, while lengthy, is very important. This
      process should include a patient interview to gather personal information, the
      chief complaint, medical history, and dental history. Extra-oral and intra-oral
      clinical examinations and a radiographic examination should be included.

PMID- 11314375
TI  - New advances in science and technology.

PMID- 11314376
TI  - In vitro analysis of distraction osteogenesis.
AB  - Distraction osteogenesis has been widely used for lengthening craniomaxillofacial
      bone. The healing process of distracted bone has been studied mainly by
      histological observation in vivo. To analyze the cellular response to the
      mechanical stress of distraction, we have established and evaluated an in vitro
      model of distraction osteogenesis using an organ culture technique. Five-week-old
      male Wistar rats were used for the experiments. The tibial bone was fractured by
      hand and fixed for 1 week by acrylic resin. After the initial healing period, the
      tibial bone was harvested and used for this study. A distraction instrument was
      devised to control the strain on the cultured bone using a micrometer. After
      distraction, the samples were histologically evaluated for ossification by
      hematoxylin and eosin stain and Alcian blue stain. As a result, the histological
      finding for the bone region at a slow rate of distraction (0.5 mm/day) was
      different from that at a rapid rate of distraction (1.0 mm/day). The
      proliferation of cartilage was inhibited at the rapid distraction rate. Thus, we
      hypothesized that mechanical stress regulated cartilaginous growth in tissue
      cultivation. Judging from this experiment, the model was useful for investigation
      of the mechanism of bone formation in distraction osteogenesis, because it was
      simple and served to isolate many factors.

PMID- 11314377
TI  - Maxillary distraction osteogenesis: a two-dimensional mathematical model.
AB  - Patients with cleft lip and palate with severe maxillary retrusion usually have a
      mandible with anterior-superior autorotation and subsequent overclosure and loss
      of the vertical facial dimension. Maxillary distraction osteogenesis can correct
      the sagittal maxillomandibular relationship and should simultaneously reestablish
      vertical dimension through maxillary vertical height increase and clockwise
      rotation of the mandible to restore facial balance. We present a two-dimensional
      mathematical model in the sagittal plane, which reestablishes sagittal and
      vertical skeletal deficiencies and proper occlusal alignment for planning
      maxillary advancement with distraction osteogenesis in patients with cleft lip
      and palate. The model is illustrated in a case of a 13-year-old boy with a
      complete bilateral cleft lip and palate and severe maxillary retrusion. The two
      dimensional mathematical model described in this article allows the surgeon and
      orthodontist to calculate in a simple and accurate way the ideal distraction
      vector to advance the maxilla to its desired position.

PMID- 11314378
TI  - Dismantling and reassembling of the facial skeleton in tumor surgery of the
      craniomaxillofacial area. History, surgical anatomy, and notes of surgical
      technique: Part 1.
AB  - In recent years, access osteotomies have been suggested to reach areas of the
      craniofacial skeleton that hitherto would not have been easily resectable. Some
      techniques of disassembling of the facial skeleton have been described in the
      past. In some cases, however, when the bony fragments were not pedicled to the
      soft tissue, reabsorption was noted. For this reason, new dismantling techniques
      with adequate blood supply to the bony fragments have been developed. Apart from
      the maxillo cheek flap, other composite flaps have been described. These flaps
      may be combined if necessary in selected cases. An overview of the surgical
      anatomy and surgical strategies will be presented. These reported techniques may
      be considered a major step forward in the treatment of deeply localized tumors in
      the craniomaxillofacial area.

PMID- 11314379
TI  - Calcium sulfate bone void filler: a review and a look ahead.
AB  - Bone grafting to augment skeletal healing has become one of the most common
      techniques in surgical practice. However, the morbidity and limited availability
      associated with autografts, and the potential for disease transmission,
      immunogenic response, and variable quality associated with allografts, have
      engendered a plethora of alternative materials. Such alternatives range from the
      simple, such as calcium sulfate and calcium phosphate materials, to the complex
      that contain allograft extracts, bone morphogenetic proteins, or other agents.
      Calcium sulfate has the distinction of being the alternative that is both one of
      the simplest as well as that which has the longest clinical history as a
      synthetic bone graft material--spanning more than 100 years. This article reviews
      the structure and function of calcium sulfate as a synthetic bone void filler and
      speculates on its future surgical role. It is anticipated that this foundation
      will also help assist in the understanding of how other bone graft alternatives
      may operate.

PMID- 11314380
TI  - Critical concepts of absorbable internal fixation.
AB  - Absorbable internal fixation implants, by virtue of their temporary in situ
      residence and variable load sharing with the healing tissues, have the potential
      to yield a clinical outcome that approaches the native state. Despite the growing
      availability and acceptance of absorbable fixation, however, many surgeons
      continue to rely on metal fixation for their patients, because, in part, of
      unfamiliarity with the technology. Although many of the principles of metallic
      internal fixation also apply to absorbable internal fixation, significant
      differences exist as well. This article presents basic background in absorbable
      technology and proposes a set of principles that may help govern the development
      and use of absorbable fixation devices in clinical practice.

PMID- 11314381
TI  - Surgical treatment of frontoethmoidal encephalocele: a case report.
AB  - This study reports a patient affected by congenital frontoethmoidal
      encephalocele. The cause of this malformation is unknown. A preoperative
      selective diagnosis evaluation is necessary. The workup should include an
      accurate clinical examination associated with radiological study (two- and three
      dimensional computed tomography, magnetic resonance imaging, etc). The aim of the
      surgical treatment is to restore the functional brain tissue in the cranial
      cavity, perform dural repair, correct bone lack and other associated facial
      malformations (hypertelorism, orbital dystopia, etc.). A multidisciplinary team
      approach is necessary to resolve the brain herniation and to correct
      splanchnocranium malformations frequently associated with encephalocele. Cranial
      flap with orbital osteotomies has been performed; this operation permits
      correction of the hypertelorism and of the orbital dystopia associated with this
      malformation. In bone reconstructions, miniplates have been used as fixation
      devices. In adults we generally use titanium, but resorbable devices are required
      in children because of growing tissues. A restoration of craniofacial
      malformations with good aesthetic and functional results is achieved with early
      surgery.

PMID- 11314382
TI  - Spontaneous bone healing in the rabbit.
AB  - Cranioplasty is the most common method for correcting cranial defects. A number
      of innovations have been made to optimize bone repair. Before their use in
      humans, extensive animal trials must be performed to establish efficacy. However,
      the literature provides only scant and inconsistent data regarding animal
      controls. The purpose of this study, therefore, was to determine the critical
      size cranial defect in the rabbit model. Cranial defects ranging from 0.5 to 1.5
      cm were created in 18 New Zealand White rabbits. The rabbits were then killed at
      9 and 18 weeks and the defects examined using CT imaging and histologic analysis
      to determine bone healing. It was determined that cranial defects greater than
      1.5 cm failed to heal spontaneously. Thus, the critical size cranial defect in
      the rabbit model is 1.5 cm.

PMID- 11314383
TI  - Distraction lengthening of the mandibular costochondral graft: a precautionary
      note.
AB  - Distraction osteogenesis of bone-grafted mandibles has been shown to occur
      without undue difficulties in bone regeneration and healing. In the patient with
      hemifacial microsomia for which early costochondral graft reconstruction has been
      done, secondary distraction lengthening may still be needed eventually. It is
      important to assess preoperatively that the superior portion of the graft is
      properly positioned against the residual glenoid fossa to prevent excessive
      superior movement of the proximal mandibular segment during distraction. The case
      presented clearly illustrates this unique distraction phenomenon.

PMID- 11314384
TI  - Internal craniofacial distraction with biodegradable devices: early stabilization
      and protected bone regeneration.
AB  - Internal craniofacial distraction has several advantages over distraction with
      external devices. The scars may be less conspicuous; the devices are buried and
      therefore easier for patients to tolerate; and the devices are more rigidly
      secured to bone, preventing uncontrolled rotation of the advancing segments.
      There are several types of internal devices. The Modular Internal Distraction
      System developed by one of the authors (S.R.C.) and Stryker-Leibinger, Inc. has
      had widespread use for midface distraction, but requires a substantial surgical
      procedure for device removal. This is justified in selected children with
      syndromic craniosynostosis, who frequently need secondary orbitocranial
      reconstruction at the conclusion of distraction with any type of device. It would
      be preferable to develop a device that would retain the positive characteristics
      of the Modular Internal Distraction system, while allowing easy removability.
      Moreover, the entire distraction procedure would benefit from a technique that
      would assist in bone regeneration within the distraction gap. Such a
      biodegradable, stabilizing device may enable early explanation, accelerating the
      recovery period, while providing fixation of the distraction gap and protected
      bone regeneration. Accordingly, we have developed a new, biodegradable
      distraction device with Macropore, Inc. that may be used with the Modular
      Internal Distraction system to permit easy removability of the device without the
      need for a large operation for exposure. Second, we have developed a
      biodegradable stabilizer that permits earlier removal of the distraction device
      while providing simultaneous fixation and protected bone regeneration. Last, we
      have demonstrated the feasibility of midcourse correction of the distraction
      procedure, should this be necessary for whatever reason.

PMID- 11314385
TI  - Schwannoma of the parapharyngeal space.
AB  - A schwannoma (or neurilemmoma) of the parapharyngeal space is a rare tumor in the
      head and neck region arising from the sheath of cranial nerves and/or the
      sympathetic chain. In the early stages of growth, there is usually a lack of
      symptoms because of the anatomical localization and slow growth of the tumor. The
      large dimension of the mass at presentation makes it difficult to perform a
      functional surgery, and in many cases the operation worsens the nerve status. The
      choice of surgical approach is of paramount importance in both preserving nerve
      function and achieving vascular control. The authors report a case and discuss
      the English literature.

PMID- 11314386
TI  - Spontaneously infected cephalohematoma: case report and review of the literature.
AB  - Spontaneously infected cephalohematomas are rare occurrences; only five cases
      have been reported previously. Uninfected cephalohematomas are common and usually
      resolve without treatment. However, physicians should be aware that
      cephalohematomas are potential sites for infection and may require aspiration for
      diagnosis and treatment. Untreated infected cephalohematomas may lead to
      osteomyelitis, epidural abscess, or subdural empyema. We present a case of a
      spontaneously infected cephalohematoma with an associated osteomyelitis which was
      successfully managed with drainage and long-term antibiotics. A review of the
      literature is also presented.

PMID- 11314387
TI  - Zygomaticomaxillary fracture repair with resorbable plates and screws.
AB  - The use of nonmetallic plate and screw fixation composed of a resorbable
      copolymer of poly L-lactic acid and polyglycolic acid (LactoSorb) for the repair
      of isolated malar fractures was studied in 53 patients. Other than technique
      variations in application for screw insertion and plate adaptation, no clinical
      differences were observed in intraoperative bone stability or postoperative long
      term results from prior experience with traditional metal devices. No occurrences
      of postoperative infection, soft-tissue swelling, or maxillary sinusitis occurred
      in this series with a 6-month to 2-year follow-up.

PMID- 11314388
TI  - Intraosseous hemangioma of the orbit.
AB  - Intraosseous hemangiomas of the orbit are very rare tumors. A case of cavernous
      hemangioma of the superolateral orbital rim is presented. A 45-year-old woman had
      a 1-year history of progressive swelling in the left lateral brow area. A
      computed tomography scan showed a well-marginated osteolytic lesion on the
      frontal bone near the frontozygomatic suture. The lesion was thought to be
      fibrous dysplasia, and the patient underwent tumor excision. The histological
      diagnosis was cavernous hemangioma. Cavernous spaces were filled with blood
      between the bony trabeculae. The spaces were lined by benign flattened
      endothelium. Intraosseous hemangioma should be suspected when a patient presents
      with an enlarging mass fixed to bone around the orbit.

PMID- 11314389
TI  - Bilateral cleft lip and palate and limb deformities: a presentation of amniotic
      band sequence?
AB  - We report a case of a child born with bilateral complete cleft lip and palate,
      absence of the left lower leg, complete absence of the right arm, and absence of
      the second and third distal phalanges of the right foot. The child had no other
      associated abnormalities. Prenatal ultrasonography recognized the cleft lip and
      palate but failed to appreciate the limb deformities. Although this specific
      constellation of abnormalities has not been previously reported in the English
      literature, it may represent an amniotic band sequence or two unrelated
      anomalies. However, unlike the vast majority of patients with amniotic band
      sequence described, there were no associated bizarre facial clefts or cranial
      defects. The case history and a review of the literature will be presented, with
      emphasis placed on categorization of these specific anomalies.

PMID- 11314390
TI  - Cervical tumor by ectopic salivary gland.
AB  - Heterotopic salivary tissue is a rare lesion, although most authors agree that
      anomalous embryologic development of salivary tissue is the main cause. One case
      of cervical tumor by ectopic salivary gland is reported, and existent literature
      is reviewed. A 26-year-old woman was operated on for a cystic tumor in the
      midline of the neck diagnosed as thyroglossal cyst in the hyoid region. After
      Sistrunk operation, the recurrence was immediate. A second operation was
      performed, and a solid tumor located between muscles of the tongue was resected.
      A long tract opening in recurrent cervical cystic tumor was also removed. No
      recurrence was evident at 1 year after surgery. Pathological examination of the
      excised mass revealed an ectopic salivary gland with serous and mucinous acini
      located between muscles of the tongue. This is a rare case report of a cervical
      fistula by ectopic salivary gland surrounded by muscles of the tongue draining
      into a cystic tumor in the hyoid midline lesion. Recurrence of thyroglossal cyst
      after a correct surgical resection must be suspected as an ectopic salivary
      tissue. Also when a cystic neck tumor is present, an ectopic salivary gland must
      be suspected.

PMID- 11314391
TI  - Complete congenital bony syngnathia in a case of oromandibular limb hypogenesis
      syndrome.
AB  - Congenital fusion of the maxilla and mandible (syngnathia) is rare and can
      present in a wide range of severity from single mucosal bands (synechiae) to
      complete bony fusion (synostosis). Congenital synostosis of the mandible and
      maxilla is even less common than synechiae, with only 19 cases reported in the
      literature. Most of them have presented as an incomplete, unilateral fusion. Only
      three of the reported cases showed more extensive but still incomplete,
      intermaxillary bony fusion. We present a case of complete bony fusion of the
      maxilla and mandible associated with a cleft palate, hypoglossia, micrognathia,
      unilateral choanal atresia, and limb abnormalities as a feature of oromandibular
      limb hypogenesis syndrome. Details of operative management are presented.

PMID- 11314392
TI  - Re: Comparison of the morphology of the " cleft face" and the normal face:
      defining the anthropometric differences.

PMID- 11314393
TI  - Koch goes to dental school.

PMID- 11314394
TI  - A new customized lingual indirect bonding system.

PMID- 11314395
TI  - Passive mandibular expansion: individualizing archform.

PMID- 11314396
TI  - Reducing cross-contamination from spools.

PMID- 11314397
TI  - Use of a modified Quad Helix in early interceptive treatment.

PMID- 11314398
TI  - A psychological approach to thumbsucking.

PMID- 11314399
TI  - A new bracket-positioning instrument.

PMID- 11314401
TI  - Absolute anchorage in orthodontics: direct and indirect implant-assisted
      modalities.

PMID- 11314400
TI  - Infection control for curing lights.

PMID- 11314402
TI  - Lingual orthodontics combined with orthognathic surgery in a skeletal Class III
      patient.

PMID- 11314403
TI  - Clinical comparison of the bond failure rates between fluoride-releasing and non
      fluoride-releasing composite resins.

PMID- 11314404
TI  - Molar distalization with a modified distal jet appliance.

PMID- 11314405
TI  - Interproximal stripping for the treatment of adult crowding.

PMID- 11314406
TI  - Alignment of blocked-out maxillary lateral incisors.

PMID- 11314407
TI  - Composite crown-form crowns for severely decayed primary molars: a technique for
      restoring function and esthetics.
AB  - Current developments in esthetic dentistry center around new techniques and
      materials that improve the ability of the clinician to provide esthetic services.
      This article describes a step-by-step method of placing composite crown-form
      crowns on severely decayed primary mandibular molars. The described technique
      allows for restoring, as close as possible, form and function lost to caries in
      an esthetic mode in cases of severely decayed primary molars that would have
      required stainless steel crowns had they been treated traditionally.
      Disadvantages of this treatment mode are that dryness may not be prevented in the
      proximal margins, especially where subgingival carious involvement is encountered
      and the margin areas may be contaminated with gingival fluid or blood. Although
      no long-term follow-up has been reported for the technique, when strong
      opposition by the parent or child to the stainless steel crown is encountered,
      and a desire for esthetic restoration is strongly expressed, the composite crown
      form crowns may be considered as an alternative.

PMID- 11314408
TI  - A new method in reminder therapy technique for ceasing digit sucking habit in
      children.
AB  - The parents' task in preventing the practice of digit sucking habit in children
      during night time is difficult. The present article introduces a new method
      called "long sleeve gown". The gown has the advantage of making it difficult for
      the child to get his/her hand out from the sleeve so that the child cannot suck
      his/her digit during sleeping.

PMID- 11314409
TI  - The management of traumatic ankylosis during orthodontics: a case report.
AB  - Dental ankylosis may be a significant complication in orthodontic clinical
      practice. This case report describes the management of a malocclusion,
      complicated by an ankylosed maxillary central incisor, which arose during
      orthodontic treatment, following an acute traumatic injury. The use of the
      ankylosed incisor in successfully managing the significant Class II division 1
      malocclusion is described.

PMID- 11314410
TI  - Ferric sulfate as pulpotomy agent in primary teeth: twenty month clinical follow
      up.
AB  - Seventy primary molar teeth, carious exposed, symptom free, without any sign of
      root resorption in children aged from 3 to 6 years (main age 4.3 yr) were treated
      with conventional pulpotomy procedures. Ferric sulfate 15.5% solution (applied
      for 15 second for 35 teeth) and formocresol solution (five minute procedure of
      Buckley's formula for next 35 teeth) have been used as pulpotomy agents. In both
      groups, pulp stumps were covered with zinc-oxide eugenol paste. Permanent
      restorations were stainless steel crowns. Clinical check up was every three
      months and radiographic follow-up time was six and twenty months after treatment.
      Our results within this period revealed 100% clinical success rate in both
      groups. Radiographic success rate was in both groups 97.2%, while in 2.8% cases
      has shown internal root resorption. On the basis of these results, we can
      recommend ferric sulfate as a pulpotomy agent in primary teeth in substitution
      for formocresol at the moment.

PMID- 11314411
TI  - An in vitro study of microleakage of pit and fissure sealants in the presence of
      occlusal forces.
AB  - The purpose of this study was to evaluate the effect of load on microleakage of
      pit and fissure sealants. In the first phase of the study load of maximal force
      (F = 880 N) on central and peripheral enamel was applied. Three groups of ten
      specimens were tested for microleakage. Group A no application of load, Group B
      application of load on the central pit of the tooth, and Group application of
      load on the peripheral enamel 2.5 mm away from the margin of the tooth, at the
      level of dentinoenamel junction. The results of that study showed significant
      increase of microleakage on the peripheral sealed enamel, as well as enamel
      microcracks. So, in the phase II sixty wisdom teeth were sealed with Ultra seal
      XT plus and load of different magnitude was applied on the peripheral enamel. The
      specimens were thermocycled for 500 cycles at 5 degrees C and 55 degrees C with a
      dwell of 30 seconds at each temperature prior to load application. Six groups of
      ten specimens were tested for microleakage under load. The force was applied at
      the peripheral enamel, 2.5 mm away from the margin of the tooth, at the level of
      dentin-enamel junction in cross-section view. Group A: F = 0 N; Group B: F = 300
      N; Group C: F = 400 N; Group D: F = 500 N; Group E: F = 600 N; Group F: F = 700
      N. Microleakage was scored as distance of dye penetration with 0 = no
      microleakage and 3 = microleakage to underlying fissure. A linear regression
      statistics was used with R-squared of 0.31. The groups with load applied (B, C,
      D, E, F) showed statistically significant results (p < 0.05) compared with group
      A (F = 0 N). Both, the magnitude of the force and tooth morphology may influence
      the degree of microleakage observed after the placement of sealants.

PMID- 11314412
TI  - Enameloplasty effects on microleakage of pit and fissure sealants under load: an
      in vitro study.
AB  - Enameloplasty has been implicated in the successful application of pit and
      fissure sealants. The present study aimed to evaluate the effect of enameloplasty
      technique on microleakage of sealants when occlusal force was applied on the
      teeth. The study also allowed a direct comparison of the effectiveness of
      enameloplasty, when two different burs were used. Six groups of ten human
      extracted wisdom teeth were tested. Group A: no load, conventional (no
      enameloplasty--control); Group B: no load, enameloplasty 1/2 round bur (Brasseler
      USA); Group C: no load, enameloplasty diamond fissure bur REF/UP 791 (Ultradent);
      Group D: load 500 N, conventional, Group E: load 500 N, 1/2 round bur; Group F:
      load 500 N, diamond fissure bur. Specimens were thermocycled for 500 cycles at 5
      degrees C and 55 degrees C with a dwell time of 30 seconds after load
      application. Microleakage was scored as distance of dye penetration with 0 = no
      microleakage and 3 = microleakage to underling fissure. The Kruskal-Wallis One
      Way Anova and Mann-Whitney U test showed group D having the greatest degree of
      microleakage statistically significant (p < 0.05) comparing with other groups.
      Sealants prepared with the conventional technique (A, D) had statistically
      significant differences in microleakage with those prepared with enameloplasty
      (B, C, E, F) (p = 0.01). Enameloplasty in groups with no load (B, C) did reduce
      microleakage, but not significantly (p = 0.3). However, loaded teeth with
      enameloplasty appeared to perform superior, as compared to those without (p =
      0.005). Regarding the effect of load, teeth without load (Groups A, B, C) were
      found to have significantly less microleakage than teeth where mechanical force
      had been applied (Groups D, E, F), (p = 0.01). Microleakage in Group A
      (conventional technique without load) was significantly less than microleakage in
      Group D (conventional technique with load), (p = 0.04). However, load did not
      seem to influence microleakage when enameloplasty had been performed. This
      finding was true for both round bur enameloplasty (p = 0.29), and fissure bur
      enameloplasty (p = 0.26). There was no statistically significant difference
      between Groups B, E (round bur) and C, F (fissure bur) (p > 0.05), or between
      Groups B and C (p > 0.05) and between Groups E and F (p > 0.05). The results of
      the study indicated that enameloplasty reduced microleakage of pit and fissure
      sealants, especially when load was applied to teeth, irrespective of what bur was
      used to enlarge the fissure, as there was no statistical significant differences
      between the round and fissured diamond burs. The application of occlusal force to
      the tooth produces significantly more microleakage, unless enameloplasty is
      performed.

PMID- 11314413
TI  - An evaluation of the bond strengths to enamel of two fissure sealants.
AB  - The objective of this study was to carry out a comparative evaluation of the bond
      strength to enamel of two present-day fissure sealants, Helioseal and Concise;
      good adhesion of the material to the tooth surface is one of the requisites for
      the success of this preventive technique. To this end, 16 caries-free human
      premolars extracted for orthodontic reasons were used. Proximal, mesial, and
      distal surfaces were treated and studied. Bond strength was evaluated by the
      application of compression forces (Instron) at a velocity of 0.5 mm/mm. The
      overall results obtained do not show significant differences between the two
      materials.

PMID- 11314414
TI  - Comparative evaluation of marginal integrity of two new fissure sealants using
      invasive and non-invasive techniques: a SEM study.
AB  - In this era of preventive dentistry, many dental materials used for prevention of
      dental diseases are available. Since last few decades efforts are being directed
      towards prevention of dental caries which is one of the major dental diseases
      tormenting mankind. The main avenues available are plaque control, use of
      systemic and local fluorides and use of fissure sealants. There are many factors
      that contribute towards a successful sealant restoration such as properties of
      enamel, duration of etching, acid used for etching, manipulative variables.
      However, one of the prime factors governing the efficacy and life expectancy of a
      sealant is the marginal adaptability. This study was carried out on a total of 40
      intact premolar teeth, which were divided in four main groups and subjected to
      evaluation under Scanning Electron Microscope. The parameters checked were the
      width and the number of marginal gaps. The results obtained showed that Teethmate
      had better marginal integrity and favored the use of invasive technique over non
      invasive technique.

PMID- 11314415
TI  - Fluoride levels in breast milk and infant foods.
AB  - The aim of the present study is to determine the fluoride concentrations of
      breast milk, several milk formulations, cow's milk and yogurt shake in a
      nonfluoridated area, in order to estimate the fluoride intake of infants and
      evaluate fluoride supplementation suggestions. Breast milk samples were collected
      from 57 lactating mothers. Ten brands of milk formulations, 9 different brands of
      cow's milk and 3 brands of yogurt shake were purchased from the market. Fluoride
      concentrations of the samples were analyzed using a specific fluoride electrode.
      The average fluoride level was 0.019 +/- 0.004 ppm in breast milk, 0.022 +/-
      0.007 ppm in cow's milk and 0.022 +/- 0.003 ppm in yogurt shake. Fluoride levels
      of milk formulations prepared by distilled water were ranging between 0.118 to
      0.021 ppm. It is concluded that in non-fluoridated areas, fluoride intake of
      infants from the above sources is not very high and fluoride supplements may be
      prescribed.

PMID- 11314416
TI  - Formation of alkali-soluble fluoride on the surface of human dental enamel after
      treatment with fluoridated gels: influence of the pH variation and of the
      treatment time.
AB  - The aim of this study was to quantify, in vitro, the formation of CaF2 after the
      application of three fluoridated gels: one neutral, one acidulated and another
      highly acidulated, on a bovine enamel dental surface treated with a Dijkman's
      demineralizing solution (1990). 145 sections were utilized, obtained from 145
      sound teeth and divided into seven groups: C (enamel without treatment); FN1
      (enamel demineralized and treated with neutral gel for 1 minute); FN4 (enamel
      demineralized and treated with neutral gel for 4 minutes); FFA1 (enamel
      demineralized and treated with acidulated gel for 1 minute); FFA4 (enamel
      demineralized and treated with acidulated gel for 4 minutes); FAA1 (enamel
      demineralized and treated with highly acidulated gel for 1 minute) and FAA4
      (enamel demineralized and treated with highly acidulated gel for 4 minutes). The
      formation of CaF2 was analyzed by SEM and chemically by Caslavska's method
      (1975). The average and standard deviations from the groups studied were
      respectively: C-0.63; 0.38; FN1-23.06; 16.52; FFA1-54.11; 49.00; FAA1-43.87;
      32.66; FN4-34.92; 23.00; FFA4-67.91; 42.36; FAA4-56.03; 38.96. (Mann-Whitney non
      parametric test). The time of application did not interfere in the CaF2 formation
      from the acidulated and highly-acidulated gels. A minor concentration of fluoride
      and amount of pH from highly-acidulated gel did not affect the higher formation
      from the CaF2 in relation to the acidulated gel in both cases when the
      application was evaluated.

PMID- 11314417
TI  - Occlusal caries formation in vitro: comparison of resin-modified glass ionomer
      with fluoride-releasing sealant.
AB  - The purpose of this laboratory study was to evaluate caries-like lesion formation
      in occlusal enamel adjacent to a light-cured resin-modified glass ionomer
      utilized as a pit and fissure sealant and a conventional light-cured, fluoride
      releasing sealant. Fluoride-free prophylaxis was done on occlusal surfaces of 12
      caries-free mandibular molar teeth that had not been exposed to the oral cavity.
      Occlusal surface morphology was examined by SEM on the uncoated specimens. Each
      tooth was then sectioned into 2 portions buccolingually, producing mesial and
      distal tooth halve. Occlusal surfaces of mesial tooth halves were prepared for an
      experimental light-cured resin-modified glass ionomer (RMG) sealant (PH-SE II,
      ESPE), and for comparison, a light-cured fluoride-releasing pit and fissure (PFS)
      sealant (Helioseal F, Ivoclar) was placed on occlusal surfaces of the
      corresponding distal tooth halves. The sealed occlusal surfaces were examined
      uncoated by SEM to compare RMG and PFS adaptation. After thermocycling in
      artificial saliva, caries-like lesions were formed in the occlusal surfaces
      adjacent to RMG and PFS. Longitudinal sections were taken for comparison of
      lesion formation adjacent to RMG and PFS. Mean lesion depths in occlusal surfaces
      were 64 +/- 17 mm for RMG, and 116 +/- 27 mm for PFS (p < 0.05, paired t-test).
      Occlusal lesions terminated at the point where bonding occurred between the
      occlusal enamel and RMG or PFS. SEM surface topography demonstrated adequate
      adaptation of the materials with obliteration of the typical pit and fissure
      surface morphology by both RMG and PFS. While both the resin-modified glass
      ionomer and fluoride-releasing sealant materials protected the pit and fissure
      enamel from caries development, the resin-modified glass ionomer reduced the
      extent of caries involvement in the adjacent unsealed occlusal incline enamel,
      when compared with the resin sealant.

PMID- 11314418
TI  - Gallium alloy versus high copper amalgam: a comparative evaluation of corrosion
      resistance and microleakage in the primary teeth.
AB  - In vivo corrosion and in vitro microleakage of a gallium based and a high copper
      amalgam alloys were evaluated. Twenty-five primary molars each were restored with
      Galloy and DPI alloy respectively and evaluated, over a period of three months,
      for various aspects of corrosion in the oral cavity. Additionally ten primary
      molars were utilized for evaluation of microleakage by dye penetration after
      having them restored with the two materials. Gallium alloy restorations showed
      better marginal adaptation, clinically when compared to amalgam restorations. No
      significant difference was observed for the degree of microleakage around gallium
      alloy and amalgam restorations.

PMID- 11314419
TI  - Ameloblastic fibroma in the midline of mandible: a case report.
AB  - The ameloblastic fibroma (AF) is a rare benign mixed odontogenic tumor. It is
      composed of both epithelial and mesenchymal elements, but lacks of any calcified
      dental structures. Most of these tumors occur in the mandible and appears
      preferentially in the posterior portion of the dental arch with molar area
      predominates over premolar area. It is important to differentiate the lesion from
      ameloblastoma, since unlike the latter, it does not exhibit a locally invasive
      growth pattern. It is a well-circumscribed lesion and does not require the
      radical excision that may be necessary to effect cure with ameloblastoma. The
      present case report describes a 15-year-old patient with an ameloblastic fibroma
      in the symphysis of the mandible, a rare reported site. In the beginning of the
      article an extensive review of the previously published literature on
      ameloblastic fibroma has been made. In the later part, the diagnosis,
      differential diagnosis, histology and therapeutic procedures and postoperative
      follow up of the present case have been described.

PMID- 11314420
TI  - Fusion of the permanent maxillary right incisor to a supernumerary tooth in
      association with a gemination of permanent maxillary left central incisor: a
      dental, genetic and dermatoglyphic study.
AB  - The relationship between fusion of the permanent maxillary right central incisor
      to a supernumerary tooth in association with gemination of permanent maxillary
      left central incisor and dermatoglyphics were investigated.

PMID- 11314421
TI  - Hurler syndrome: a case report.
AB  - Hurler syndrome is an inherited disorder of mucopolysaceharide metabolism, which
      is caused by a defect in genetically controlled pathways of lysosomal
      degradation. It represents the classical prototype of mucopolysaccharide
      disorder. An interesting case of a three and a half-year old boy with a rare
      combination of skeletal, neurological, ophthalmologic, and dental findings is
      presented. It is a rare syndrome with a very low prevalence of 1:100,000 births
      and as such the clinician should be aware of this syndrome.

PMID- 11314422
TI  - Changes in interarch distance and condylar position related to loss of occlusal
      support for partially edentulous patients. A pilot study.
AB  - Changes of interarch distance and condylar position related to loss of the
      posterior occlusal support were investigated. Five subjects, whose mandibular
      premolars and molars needed to be restored, were selected. Their experimental
      prostheses were removed in sequence from the most posterior to anterior. The more
      the posterior occlusal support decreased, the more the interarch distance in the
      first molar region decreased. When the occlusal supports of both mandibular
      molars and premolars were absent, the condylar position moved superio-anteriorly.
      The occlusal support of the first molar showed a significant role in maintaining
      the intercuspal and condylar position.

PMID- 11314423
TI  - Zirconia-TZP and alumina--advanced technologies for the manufacturing of single
      crowns.
AB  - All-ceramic crowns based on Zirconia-TZP-frameworks should have advantages in
      comparison to copings of Alumina (PROCERA-AllCeram) because of their mechanical
      properties. Zirconia-TZP-frameworks were manufactured after optical digitising
      using a modified Precident-DCS-System. The mean fracture strength and the
      vertical marginal discrepancy of Zirconia-TZP-frameworks and Alumina-copings
      (PROCERA-AllCeram) were determined. Additionally the bonding strength of suitable
      veneering ceramics on pre-treated Zirconia-TZP surfaces was examined using the
      scratch test and the shear bonding strength. The results show that the bonding
      between Zirconia-TZP and the veneering ceramics as well as the precision of fit
      of the veneered crowns are comparable with established systems.

PMID- 11314424
TI  - The role of saliva in regurgitation erosion.
AB  - It has been suggested that salivary characteristics are important in the
      progression of erosion. The aim of this investigation was to measure salivary
      parameters in 22 patients with erosion, 10 with normal (non-pathological) levels
      of reflux (Group I) and 12 with previously diagnosed pathological levels of
      gastro-oesophageal reflux (Group II). A further 10 subjects without evidence of
      erosion and no history of reflux disease acted as controls (Group III). No
      statistically significant differences in salivary flow rate, buffering power or
      the concentrations of calcium, phosphorus and fluoride were detected. The results
      suggest that variation in the characteristics of unstimulated and stimulated
      saliva collected during waking hours do not have a major role in erosion.

PMID- 11314425
TI  - Assessing the quality of shoulder preparations for metal ceramic crowns.
AB  - Previous work by the authors indicates a tendency for academic clinicians to
      under prepare and over angle shoulder preparations for metal ceramic crowns. This
      has implications for the final restoration in terms of contour, appearance and
      strength. This study analysed ninety six preparations, forty eight in vitro and
      forty eight in vivo, performed by six clinicians. The results show a mean
      shoulder width of 0.804 +/- 0.274 mm and a mean shoulder angle of 116 +/- 18
      degrees for preparations performed in vitro; and 0.892 +/- 0.337 mm and 121 +/-
      24 degrees for preparations performed in vivo. Thus, despite recommendations that
      such crowns should have 1-1.5 mm, 90 degrees shoulders, many of the preparations
      studied here fell short of this, indicating a lack of consistency in preparation
      geometry and adherence to the perceived 'ideal' preparation for a metal ceramic
      crown.

PMID- 11314426
TI  - Demonstration of "vertical barrelling" using profilometry.
AB  - The aim of this study was to demonstrate the extent of tooth flexure under axial
      loading using profilometry. Fifteen extracted human permanent upper premolar
      teeth were embedded in hard die stone and divided into 3 groups. One group was
      left unprepared, the second group had artificial cervical saucer shaped lesions
      prepared and the final group had artificial cervical notch lesions prepared. The
      labial profile was taken using a diamond stylus mounted in a Profilometer. The
      teeth were then loaded in an axial direction to circa 670 N and the labial
      surface re-profiled 20 s after loading. The results indicate that changes occur
      in the labial profile of premolar teeth that are subjected to axial loading which
      could be considered to represent vertical barrelling. Changes in the profile of
      the artificial saucer and notch lesions prepared at the cervical region suggest
      that stresses would be generated on restorations of these lesions.

PMID- 11314427
TI  - Case report: temporary restoration for a single tooth implant prosthesis with
      adverse axial inclination of the fixture.
AB  - Providing an acceptable temporary restoration can be a challenge on a single
      implant where surgical considerations have dictated an adverse axial alignment.
      Prefabricated temporary abutments do not incorporate compensation for such
      implant positions. A temporary restoration can serve multiple functions. This
      case report describes a technique to provide an acceptable temporary restoration
      for a malaligned single tooth implant.

PMID- 11314428
TI  - Measurement of changes in dimensions of resorbing alveolar bone: description of a
      method.
AB  - This study evaluated a cast-measuring device used to investigate effects of
      augmenting fresh extraction sockets with dense hydroxyapatite granules. Following
      reproducible location of the casts, alterations in ridge tracings were related to
      radiographically determined ridge height alterations. A randomised controlled
      study compared two groups of immediate complete denture wearers. One group
      received conventional immediate dentures, the other received immediate complete
      dentures after dense hydroxyapatite implantation into canine sockets. Ridge
      height alterations with time were recorded from radiographs. Alterations in ridge
      form were recorded from several models transferred reproducibly to a mounting jig
      attached to a profiling apparatus. Further, the osteo-retentive ability of the
      hydroxyapatite in the sockets was seen to be close to significance (after six
      months width differences, in the canine region: P = 0.059, LHS, and P = 0.065,
      RHS).

PMID- 11314429
TI  - Psychosocial issues following a positive result of genetic testing for BRCA1 and
      BRCA2 mutations: findings from a focus group and a needs-assessment survey.
AB  - BACKGROUND: About 5% of cases of breast cancer and 10% of cases of ovarian cancer
      are due to an inherited predisposition. Since 1994 it has been possible to test
      some people at high risk for inherited mutations to the BRCA1 and BRCA2 genes.
      The purpose of our study was to explore how genetic testing had affected people
      found to have a BRCA mutation and their families, and to determine whether there
      was interest in a peer-support group. METHODS: All people given positive results
      of genetic testing for BRCA1 and BRCA2 mutations at either of 2 familial breast
      cancer clinics were invited to participate in a focus group and complete a
      questionnaire. Those who did not attend or who received positive results after
      the focus group were mailed the questionnaire. Information was sought on the
      effect of testing on cancer risk perception and worry about cancer, communication
      of test results to family members, attitudes toward surveillance and toward
      prevention options, satisfaction with clinical services, need for additional
      support and satisfaction with decision to undergo testing. RESULTS: Eight of the
      27 people invited to participate in the focus group attended. Sixteen of the 26
      who were mailed the questionnaire completed and returned it. Although cancer risk
      perception and worry increased after receipt of the test results, the
      participants did not regret their decision to undergo testing. Confidence in the
      efficacy of cancer surveillance was high. Prophylactic oophorectomy was much more
      acceptable than prophylactic mastectomy. Almost all (92% [22/24]) were satisfied
      with the clinical services they had received; however, all were dissatisfied with
      the lengthy wait for test results. Nine (38%) of the participants felt they would
      benefit from a support group. INTERPRETATION: Adequate resources must be made
      available to clinical programs providing BRCA1 and BRCA2 mutation testing to
      ensure appropriate pretest counselling and timely availability of results.
      Organization of support groups for people found to have the gene mutations should
      be a priority for these programs.

PMID- 11314430
TI  - Brachytherapy for prostate cancer: effective, but...?

PMID- 11314431
TI  - Mental health and primary care.

PMID- 11314433
TI  - Canada's Ebola scare over but questions just beginning.

PMID- 11314434
TI  - Getting the global picture of AIDS.

PMID- 11314432
TI  - Cervical cancer: epidemiology, prevention and the role of human papillomavirus
      infection.
AB  - Organized screening has contributed to a decline in cervical cancer incidence and
      mortality over the past 50 years. However, women in developing countries are yet
      to profit extensively from the benefits of screening programs, and recent trends
      show a resurgence of the disease in developed countries. The past 2 decades have
      witnessed substantial progress in our understanding of the natural history of
      cervical cancer and in major treatment advances. Human papillomavirus (HPV)
      infection is now recognized as the main cause of cervical cancer, the role of
      coexisting factors is better understood, a new cytology reporting terminology has
      improved diagnosis and management of precursor lesions, and specific treatment
      protocols have increased survival among patients with early or advanced disease.
      Current research has focused on the determinants of infection with oncogenic HPV
      types, the assessment of prophylactic and therapeutic vaccines and the
      development of screening strategies incorporating HPV testing and other methods
      as adjunct to cytology. These are fundamental stepping stones for the
      implementation of effective public health programs aimed at the control of
      cervical cancer.

PMID- 11314435
TI  - Public ignorant about telemedicine, survey finds.

PMID- 11314436
TI  - The weak connection between venous thromboembolism and air travel.

PMID- 11314437
TI  - Adverse drug reaction reporting--2000: Part 1.

PMID- 11314438
TI  - Antiparkinsonian drugs and "sleep attacks".

PMID- 11314439
TI  - Rofecoxib (Vioxx): a year in review.

PMID- 11314440
TI  - Mental illness in my backyard.

PMID- 11314441
TI  - Show some compassion.

PMID- 11314442
TI  - Screening for colorectal cancer.

PMID- 11314443
TI  - Screening for colorectal cancer.

PMID- 11314444
TI  - Screening for colorectal cancer.

PMID- 11314445
TI  - Screening for colorectal cancer.

PMID- 11314446
TI  - Screening for colorectal cancer.

PMID- 11314447
TI  - Is it health care or is it health?

PMID- 11314448
TI  - Who determines the course of a patient's treatment?

PMID- 11314449
TI  - Jehovah's Witnesses and artificial blood.

PMID- 11314450
TI  - Military MDs know where their duty lies.

PMID- 11314451
TI  - Systematic overview of the evidence for brachytherapy in clinically localized
      prostate cancer.
AB  - BACKGROUND: Brachytherapy (permanent implantation of radioactive seeds) has
      emerged as an alternative to existing standard therapy with radical prostatectomy
      or external beam radiotherapy in the treatment of clinically localized (T1 and
      T2) prostate cancer. The Genitourinary Cancer Disease Site Group of the Cancer
      Care Ontario Practice Guidelines Initiative examined the role of brachytherapy in
      treating clinically localized prostate cancer. METHODS: A systematic review of
      articles published from 1988 to April 1999, retrieved through a search of MEDLINE
      and CANCERLIT databases, was combined with a consensus interpretation of the
      evidence in the context of conventional practice. RESULTS: Although there were no
      randomized trials comparing brachytherapy with standard treatment, evidence was
      available from 13 case series and 3 cohort studies. Rates of freedom from
      biochemical failure (biochemically no evidence of disease [bNED]) varied
      considerably from one series to another and were highly dependent on tumour
      stage, grade and pretreatment serum prostate-specific antigen (PSA) levels.
      Results in patients with favourable tumours (T1 or T2 tumour, Gleason score of 6
      or lower, serum PSA level of 10 ng/mL [microgram/L] or less) were comparable to
      those in patients undergoing radical prostatectomy. Acute urinary retention was
      reported in 1%-14% of patients. Long-term sequelae occurred in less than 5% of
      patients and included urinary incontinence, cystitis, urethral strictures and
      proctitis. Sexual potency was maintained after implantation in 86%-96% of
      patients. INTERPRETATION: At present, there is insufficient evidence to recommend
      the use of brachytherapy over current standard therapy for localized prostate
      cancer. Brachytherapy using transrectal ultrasound guidance for seed implantation
      is promising in terms of freedom from biochemical failure in selected patients
      with early-stage prostate cancer. Brachytherapy is currently available outside of
      clinical trials, but whenever possible patients should be asked to participate in
      randomized trials comparing brachytherapy and current standard therapy.
      Brachytherapy should be available to selected patients (those with T1c or T2a
      tumours, a Gleason score of 6 or lower and a serum PSA level of 10 micrograms/L
      or less), after discussion of the available data and potential adverse effects.

PMID- 11314452
TI  - A randomized clinical trial of care for women with preterm labour: home
      management versus hospital management.
AB  - BACKGROUND: Preterm labour occurs in about 10% of all pregnancies and is the most
      important cause of premature birth. Women with preterm labour are admitted to
      hospital to have the contractions stopped. Thereafter, many women remain in
      hospital until delivery. We conducted a randomized clinical trial to compare
      hospital care with home care of women who had been admitted to hospital for
      preterm labour. METHODS: After they had received treatment for an acute episode
      of premature labour, women at 2 regional perinatal centres associated with
      teaching hospitals were randomly assigned to home care or hospital care. Eligible
      women (n = 250) were aged 18 years or older, lived within 50 km of the hospital,
      had a gestational age between 20 and 35 weeks, had no prior preterm delivery and
      were experiencing their first episode of preterm labour and first admission to
      hospital for preterm labour. Analysis was by intention to treat. RESULTS: There
      were no significant differences between the 2 groups in mean gestational age at
      delivery (home: 37.52 weeks, hospital: 37.50 weeks) or in mean birth weight
      (home: 2974 g, hospital: 3020 g). There were no significant differences between
      the 2 groups with respect to the proportions of babies born before term or the
      mean duration of neonatal hospital stay, neonatal intensive care unit stay and
      intermediate care nursery stay. The mean duration of the first stay in hospital
      for the women in the home group (3.8 days) was significantly shorter than the
      mean duration for women in the hospital group (6.1 days). In addition, the mean
      duration of all maternal stays in hospital was significantly shorter for the
      women in the home group (3.7 days) than in the hospital group (5.0 days).
      INTERPRETATION: Home care management is an efficient and acceptable alternative
      to hospital care for women experiencing preterm labour.

PMID- 11314453
TI  - Prevalence of asthma symptoms among adults aged 20-44 years in Canada.
AB  - BACKGROUND: Reported prevalence rates of asthma vary within and between countries
      around the world. These differences suggest environmental factors in addition to
      genetic factors in the cause of the disease and may provide clues for preventive
      strategies. We examined the variability of asthma-related symptoms and medication
      use among adults in 6 sites across Canada (Vancouver, Winnipeg, Hamilton,
      Montreal, Halifax and Prince Edward Island) and compared our findings with those
      from sites that had participated in a recent European survey. METHODS: We used
      the same sampling strategy and standardized questionnaire as those used in the
      European Community Respiratory Health Survey (ECRHS). The 6 Canadian sites were
      selected to represent different environments with respect to climate, air
      pollution and occupational exposure. Community-based samples of 3000 to 4000
      people aged 20-44 years were randomly selected in each site. Subjects were asked
      to complete the questionnaire by mail between March 1993 and November 1994.
      Prevalence rates (and 95% confidence intervals [CIs]) of asthma symptoms, self
      reported asthma attacks and use of asthma medication were compared across the
      Canadian sites and with sites that had participated in the ECRHS. RESULTS: The
      overall response rate of those selected to receive the questionnaire was 86.5%
      (range 74.5%-92.8%). The prevalence rates of most asthma symptoms varied
      significantly among the Canadian sites. For instance, 21.9% (Montreal) to 30.4%
      (Halifax) of the men and 24.0% (Vancouver) to 35.2% (Halifax) of the women
      reported wheezing in the year before the survey. Depending on the site, 4.4% to
      6.3% of the men and 5.2% to 9.5% of the women reported an asthma attack in the
      last year, and 4.0% to 6.1% of the men and 4.9% to 9.7% of the women were
      currently using asthma medication. Prevalence rates of symptoms, asthma attacks
      and medication use did not change with age, but they were higher among women than
      among men. Compared with the results from the ECRHS sites, those from the
      Canadian sites were among the highest. INTERPRETATION: Significant variation in
      the prevalence of asthma symptoms, asthma attacks and use of asthma medication
      between Canadian sites and international sites suggests environmental influences.
      Different combinations of factors in different sites may be responsible for the
      high prevalence rates and should be the subject of further research to guide
      clinical management and public health intervention.

PMID- 11314454
TI  - Group portraits--the Dilettanti Society.

PMID- 11314455
TI  - Ramon y Cajal: a century after the publication of his masterpiece.
AB  - Santiago Ramon y Cajal published the first of the three volumes of his principal
      life's work in 1899, and published the last volume in 1904. This book remains the
      definitive work on the morphology of the vertebrate nervous system. In it, Ramon
      y Cajal describes the structure and organization of virtually all parts of the
      nervous system and discusses his theories, including the neuron doctrine and the
      law of functional polarization, which are the cornerstones of modern
      neurobiology. A century later, Ramon y Cajal's work is still fundamental to
      understanding the nervous system.

PMID- 11314456
TI  - Does using an instrument make you mathematical? Mathematical practitioners of the
      17th century.
AB  - Gaining an insight into what it meant to be a mathematical practitioner in the
      17th century is difficult. People who thought themselves mathematical included
      navigators, sundial makers and book-keepers. For some, the simple use of
      instruments was construed as mathematical; for others, this was merely a 'showing
      of tricks'. One profession reliant on mathematics was land surveying. An analysis
      of this profession throws up many interesting questions about what it meant to be
      mathematical in early modern England.

PMID- 11314457
TI  - Private science and the Imperial imagination: John Herschel's Cape voyage.
AB  - In 1833 Sir John Herschel sailed to the British Cape Colony in southern Africa.
      It was a private voyage, the purpose of which was to undertake an astronomical
      survey of the southern heavens. But his private voyage was interpreted by both
      the British Government and the British public as a voyage of Imperial scientific
      exploration. Despite Herschel's explicitly private scientific intentions, he
      nonetheless became popularly incorporated into the ranks of imperial scientific
      explorers.

PMID- 11314458
TI  - Human computers: the first pioneers of the information age.
AB  - Before computers were machines, they were people. They were men and women, young
      and old, well educated and common. They were the workers who convinced scientists
      that large-scale calculation had value. Long before Presper Eckert and John
      Mauchly built the ENIAC at the Moore School of Electronics, Philadelphia, or
      Maurice Wilkes designed the EDSAC for Manchester University, human computers had
      created the discipline of computation. They developed numerical methodologies and
      proved them on practical problems. These human computers were not savants or
      calculating geniuses. Some knew little more than basic arithmetic. A few were
      near equals of the scientists they served and, in a different time or place,
      might have become practicing scientists had they not been barred from a
      scientific career by their class, education, gender or ethnicity.

PMID- 11314459
TI  - Joseph Hooker: the making of a botanist.
AB  - Joseph Hooker became one of the most influential botanists of his day. He is best
      remembered as a friend of Charles Darwin and an early advocate of natural
      selection. However, after returning to Britain from his first major voyage,
      Hooker spent years struggling to find a paid position that would allow him to
      pursue his studies of plant classification and distribution. As he worked to
      establish himself, he also helped transform the status of botany as a discipline.
      In all his efforts, Hooker relied on a network of unpaid, colonial collectors,
      whose often-forgotten contributions to Victorian natural history are vital to the
      understanding of the professionalization of the sciences in the 19th century.

PMID- 11314460
TI  - Just before the Beagle: Charles Darwin's geological fieldwork in Wales, summer
      1831.
AB  - Darwin returned to Shrewsbury in mid-June 1831 and spent that summer learning
      geology. He made geological maps of Shropshire and visited Llanymynech and other
      localities. From 3-20th August he joined Sedgwick on his tour of North Wales;
      they geologised west of Shrewsbury before travelling through Llangollen, Ruthin,
      Conwy to Bangor finally reaching Anglesey. Darwin left Sedgwick at Menai and
      walked to Barmouth making a special visit of Cwm Idwal. He returned to Shrewsbury
      on 29th August to open the letter from Fitzroy inviting him to join the Beagle.
      During this summer Darwin gained skills in all aspects of geology, including
      chemical analysis, which were to prove vital in the development of his ideas on
      natural selection.

PMID- 11314461
TI  - Science and humanities: across two cultures and into science studies.
AB  - C.P. Snow's articulation of a two-culture divide rested on a particular view of
      science that has been elaborated and superseded by interdisciplinary science
      studies. Thus, comparisons of the 'science wars' of recent years to the Snow
      Leavis controversy fail to recognize basic structural differences between the two
      sets of debates. In this article, I present these differences and offer some
      views of what has changed in the intervening years.

PMID- 11314462
TI  - [Fighting dogs--dangerous dogs: legal situation in Bavaria].
AB  - A report is given on eight years of experience with the Bavarian legal regulation
      for the protection against dangerous dogs of 10.7.1992. The implementation of the
      regulation was a success. Since then only two cases of biting accidents are
      reported. In one case the dogs were euthanatized, in the other case they were
      taken away and given to other owners. The advantages of the regulation are seen
      in the increased responsibility of the dog owner who has to give proof of the
      peaceful character of his dog in form of an expert testimony. This lowers the
      administration costs and has revealed a preventive effect, the dog owners are
      looking more carefully after their animals to avoid any security problems.

PMID- 11314463
TI  - [Enriched cage systems for laying hens--legal minimum conditions and starting
      points for their scientific evaluation].
AB  - Recent developments in the European and national legislation regarding minimum
      standards for the keeping of laying hens will be causing changed conditions for
      egg production in the medium term. Enriched cages shall allow hens to better
      fulfill their needs than traditional battery cages. More space for the stretching
      of wings and legs, perches for resting, littered areas for scratching, pecking
      and dustbathing and nests for egg-laying behaviour shall allow layers to perform
      more of their normal behaviour patterns. However, regarding the sustainability of
      these systems there are different views and still a great lack of scientific data
      and practical experience. An overview is given on the development of European and
      national animal welfare legislation concerning laying hens, minimum requirements
      for enriched cages and the available evidence about animal behaviour, performance
      and health in these systems. Furthermore, a current project at the School of
      Veterinary Medicine Hannover on the animal welfare assessment of enriched cages,
      specifically on the Aviplus cage system, which was one of the first systems on
      the market and is in accordance with EU-directive, is introduced.

PMID- 11314464
TI  - [Current aspects of the use of automated milking systems].
AB  - Automatic milking systems offer not only a marked improvement of the working
      conditions in dairy farms but also they may be able to improve the quality of
      life of the dairy farmer, the health and performance status of the cow and the
      milk quality. The current stage of development of automatic milking systems
      indicates that there are still some deficiencies in fulfilling the requirements
      of the milk hygiene regulations, the early identification of health problems and
      allowing veterinary measures. This paper details some aspects of cow and udder
      health and milk quality under the condition of automatic milking systems by
      discussing actual problems and potential future advantages.

PMID- 11314465
TI  - [Automatic milking from a behavioral and welfare viewpoint].
AB  - Automatic milking systems have been shown to change the behaviour of cows.
      Because pre-determined milking and feeding times are eliminated, the cows must
      establish their own daily routine. They have to adapt to being milked according
      to their lactation. There are, however, indications that not all cows adapt well
      to the automatic system. Some herd members seem to have inhibitions about
      entering the milking stall. Too many cows per milking stall and a blocked milking
      system intensify the situation. Therefore, the cows must either be forced or
      attracted by food to enter the milking stall. Altogether some cows appear to be
      more stressed. Furthermore, the human-animal relationship changes due to the new
      work content. There is less manual work, more observation, and more computer
      data. The farmer needs to be well educated and must establish a new management
      program. If care is insufficient, if some herd members are less frequently
      milked, and if measures to reduce stress are not taken, it is clear that welfare
      problems could arise. Compared to milk quality and milk hygiene, technical
      solutions and regulations by law are not as important. Ethological knowledge must
      be taken into account if automatic milking is to be advantageous for both cow and
      man.

PMID- 11314466
TI  - [Animal welfare in schools--experiences from Mecklenburg-Western Pomerania].
AB  - More and more our schools are asked to include questions of animal protection in
      their curricula. So far animal-related topics have only been dealt with in the
      subjects Biology and "Sachunterricht" from a more ecological and/or economical
      point of view. Many teachers lack sufficient knowledge to teach their pupils
      topics of animal protection in a practical and interesting way. Moreover there
      exist various obstacles such as red tape problems and missing curricula that make
      it difficult to integrate questions of animal protection in our schools. That is
      why a workable structure for in-service-training including experts, teachers and
      politicians is being developed to improve the situation.

PMID- 11314467
TI  - [Mistakes in general husbandry of ornamental fish].
AB  - Mistakes in general husbandry conditions of ornamental fish can consist in
      insufficient quality of water, inadequate feeding, equipment and social structure
      and poor prophylactic measures. Clinical symptoms are generally not specific.

PMID- 11314468
TI  - [The killing of surplus and old animals in zoos].
AB  - The painless killing of animals in order to avoid considerable suffering has a
      legal basis and is sufficiently accepted by the society. The situation is,
      however, different when the matter concerns zoological gardens having on some
      occasions to put down apparently healthy animals. Since the natural populations
      of many species have almost been extinguished in the wild or are already
      eradicated, zoos play a prominent role in the ex-situ survival-breeding of many
      wild animals. This means that zoos often have self-supporting populations of
      species rather than only single individuals, as was frequently the case in the
      past. Such breeding also brings with it the possibility that animals will survive
      without the option of transferring them to other acceptable locations. In the
      wild, natural environmental factors prevent excessive population growth, whereas
      in zoos and in other protective reservations, such regulatory mechanisms are
      simply not existent. Such regulation can, however, often be achieved by animal
      transfers and other stock regulating measures. If these measures are not
      available the option of putting the animals down must be considered. Preventing
      suffering is of course the priority, as is demanded by zoos together with
      recognised animal protection organisations. This is compliant with German law and
      takes place for obvious and sensible reasons. The scientific zoological gardens
      organised in the German Zoo Directors Council discussed the problem of killing
      animals at the 1999 conference at Rostock and drafted a paper presenting its
      position on the subject. The paper argues that even under optimal husbandry
      conditions, while alternative options of breeding, planning and stabilisation of
      stock must be considered, the humane killing of animals will sometimes be
      unavoidable.

PMID- 11314469
TI  - [Supervision of rabbit husbandry--report of a public health veterinarian].
AB  - Rabbits are wide spread farm animals and pets, which are kept in the most diverse
      areas. The evaluation of rabbit husbandries in regard to animal welfare
      legislation is often complicated by different and contradictory recommendations
      of various organisations, which should partly be revised. In the following
      article some regulations and guidelines are discussed. In addition, some aspects
      for the keeping of rabbits in accordance with their behavioural needs are
      outlined, some frequent shortcomings regarding the keeping of rabbits are
      described and possibilities for taking official measures are presented.

PMID- 11314470
TI  - [The species-specific feeding of rabbits in pet husbandry].
AB  - To meet nutrient demands as well as the species specific requirements of an
      animal it is absolutely necessary to know its nutrition physiology (KAMPHUES et
      al. 1999). Characteristics of the nutrition physiology of rabbits include the
      anatomy of the intestinal tract (i.e. the teeth, the size of gut as well as the
      small intestine and colon), the special ingesting behaviour (selection, intensity
      of gnawing and chewing) and digestive processes within the intestinal tract
      (digestion by own as well as by microbial enzymes, processes of separation
      (producing soft faeces) and the excretion of digested or undigested nutrients
      (excretion via faeces or kidneys, quality of faeces). In feeding pet rabbits it
      has to be recommended, that these species do not need concentrates, but
      ingredients with higher crude fiber contents due to their origin and their
      intestinal tract. Therefore these herbivorous species should be fed with hay,
      straw or vegetables and not with concentrates exclusively. If these components
      are not offered (an usual feeding practice in rabbits kept as companion animals),
      other products rich in crude fibre have to be fed. The offer of a pressed diet in
      cube form with long fibrous ingredients would be a possibility to upgrade a
      ration poor in crude fibre. To meet the gnawing requirement of the rabbits this
      cubes should be pressed intensively. Furthermore it is advisable to exchange
      ingredients of the mixed feed with a high energy content (i.e. sunflower seeds,
      nuts) for ingredients of lower energy density (i.e. oat hulls, pelleted ground
      hay). Finally calcium oversupply has to be avoided because higher calcium intake
      may result in urolithiasis (calcium stones/concrements).

PMID- 11314471
TI  - [Farming minks--possibilities for more adequate husbandry within the current
      circumstances].
AB  - The keeping of minks in farms is widely disputed. As the present article
      illustrates, improvement in the management of farm minks can be achieved with
      relatively little effort. By implementing connecting openings between regular
      cages the area for living can easily be enlarged, moreover the structure of the
      cages will be improved. This resides in minks living in groups intensifying their
      social contacts. Analyses by "Het Spelderholt", Praktijkonderzoek
      Pluimverhouderij, Beekbergen, Netherlands show that behavioural problems can be
      significantly reduced by raising minks in adequate groups. Also the interior
      design and structure of cages is of equivalent importance reducing the occurrence
      of behavioural problems. The importance of an access to a water basin however has
      still to be investigated. One striking aspect on the subject of hygiene that has
      to be pointed out is the regular removal of faeces.

PMID- 11314472
TI  - [Breeding strategies to increase fitness in poultry].
AB  - The performance of the meat type hybrids of today is much higher than at the
      beginning of the century. Antagonistic relations between the polygenic
      performance traits and fitness are the reason why modern hybrids need optimal
      management conditions, their susceptibility to stress increased and their
      immunocompetence decreased. There will be discussed, how modern genetics is
      counteracting by using new selection techniques.

PMID- 11314473
TI  - [Man-nature-technology. Philosophical considerations of human-animal-relations].
AB  - Man's position in nature is equivocal. Man is part of nature and through
      evolution is linked to other living beings. Although an "Animal among Animals",
      nature has provided him with capabilities that separate him from all living
      beings in its realm. These comprise the ability for reflection and subsequent
      moral behavior, but also the gift (and necessity) for using technology to shape
      and subjugate his natural environment. Based upon this "Dual Nature of Man" the
      essay focuses on the web of interactions between Man, Nature and Technology.
      Modern ethics of animal protection argue in favor of extending the principle of
      equality ("To Each His Own") to include animals as well. However, the principle
      of equality is a purely formal, heuristic rule for assigning morally just
      determinations of value. It requires normative padding as far as its content is
      concerned. Consequently, the content of the principle of equality ought to be
      more closely determined in keeping with the ideal of humanity.

PMID- 11314474
TI  - [Application of paragraph 16a of the Animal Protection Act].
AB  - section 16 a of the Animal Protection Act presents difficulties from a number of
      points of view. What applies here in particular also applies to the Animal
      Protection Act in general. A look at the rulings of the Federal Administrative
      Court, which has only issued about twelve judgements regarding the Animal
      Protection Act, shows that a large number of elements of this act are still in
      need of final interpretation. One of the principal reasons for this seems to be
      that disputes involving this act only relatively rarely come up before the
      administrative courts. Furthermore, this legal provision has shortcomings and it
      not entirely easy to implement. section 16 a of the Animal Protection Act should
      at least be improved from the legal technical point of view. There is scope for
      this to be done. Legislators must use this scope within the meaning of animal
      protection defined in the law--an issue which is of great concern to us all.

PMID- 11314475
TI  - [Biology of aggression in dogs].
AB  - The science of ethology is concerned with the way external stimuli and internal
      events cause animals to fight in a particular way. The classification of dog
      breeds with respect to their relative danger to humans makes no sense, as both,
      the complex antecedent conditions in which aggressive behaviour occurs, and its
      ramifying consequences in the individual dog's ecological and social environment,
      are not considered. From a biological point of view, environmental and learning
      effects are always superimposed upon genetic influences. Based on the recent
      developments in the study of ethology, aggression of wolves (Canis lupus L.) and
      domesticated dogs (Canis lupus f. familiaris) was put into context with respect
      to other aspects of the lifestyle of wild and domestic canids. Aggressive
      behaviour does not occur in a biological vacuum. This is also true for domestic
      dogs and their relationship to human partners. Individual dogs can become highly
      aggressive and dangerous. Their development and social situation will be
      presented and discussed in case studies. Finally, there is the question about
      defining "normal aggression" versus symptoms for maladaptive aggression resp.
      danger to humans as conspecifics. It is possible to protect the safety of the
      public and at the the same time practise animal care. Effective animal control
      legislation must focus on responsible ownership and socialisation of pups f.e.
      Problems are not unique to some breeds.

PMID- 11314476
TI  - Capturing the image or taking the picture?

PMID- 11314477
TI  - Public attitudes of independent dental hygiene practice.
AB  - PURPOSE: The three main objectives of this study were to assess if the Alberta,
      Canada public perceives dental hygienists as competent to practice without the
      supervision of a dentist, whether or not they would choose to be treated by
      independent dental hygienists, and if they believed that these services should be
      covered by dental insurance. METHODS: The University of Alberta population
      research lab conducted a random digit dialing telephone survey of Alberta
      residents, regarding access to dental hygiene services and willingness to visit
      an independent dental hygiene practitioner. There were 1,202 residents (49.6%
      males and 50.4% females, 18-64 years), evenly distributed among urban and rural
      areas, who were interviewed. The estimated sampling error, at the 95% confidence
      level, was accurate + 2.9%. RESULTS: Of the respondents, 65.8% stated that they
      would visit an independent dental hygienist and that dental hygienists should
      have the ability to provide services, within their scope of practice, without
      being supervised. This response was consistent, irrespective of the geographic
      area, gender or income. When asked about their reasons for choosing an
      independent dental hygienist, 68.8% believed visiting a dental hygienist is
      important in the healthy treatment of their mouth, while 58.4% wanted the freedom
      to choose, and 56.3% believed dental hygiene care would save them money. They
      also indicated that they would visit an independent dental hygienist in a variety
      of sites, including a health center (45%), a mobile clinic (21.5%), an
      independent practice site (45%), and in a dentist's office (64.9%). Ninety-two
      percent of the respondents said that independent dental hygiene services should
      be covered by dental insurance. CONCLUSION: The results show that the public
      supports dental hygienists gaining independent practice, and that they trust the
      level of care provided by the dental hygiene profession.

PMID- 11314478
TI  - Dental hygiene self-assessment: a key to quality care.
AB  - PURPOSE: To help achieve the goal of delivering quality care to the public, this
      study applied the Theory of Reasoned Action to dental hygienists' self-assessment
      (appraisal of one's performance). This theory suggests that individuals are
      likely to exhibit a given behavior, i.e., self-assessment, when they view it
      positively and when they believe that important others think they should perform
      it. To date, no research has been conducted on the self-assessment (SA) behaviors
      of practicing dental hygienists. The following research questions were addressed:
      what/who are the (1) behavioral beliefs; (2) normative beliefs; (3) salient
      referents; (4) attitudes toward self-assessment; (5) intentions to perform self
      assessment; (6) outcomes associated with self-assessment; and (7) motivations to
      comply with self-assessment in a representative sample of dental hygienists?
      METHODS: This study consisted of two phases: Phase I, telephone interviews (N =
      30) and Phase II, a mailed survey of 600 randomly selected subjects. Interview
      responses from Phase I determined questionnaire items. Survey data analysis
      included descriptive statistics and correlations of component mean scores.
      RESULTS: A total of 273 usable surveys were returned, achieving a 46% response
      rate. Respondents valued the potential benefits of SA with a statistical mean of
      2.70 on a six point scale ranging from minus three to plus three. Attitude
      correlated strongly with intention to self-assess (R = .7455). Survey respondents
      are motivated by their own beliefs and perceived benefits of SA rather than by
      the values of others. CONCLUSION: The insights that were derived from this study
      will permit the development of strategies to enable dental hygiene educators and
      practitioners to incorporate self-assessment as part of quality assurance plans.
      Application of well-developed self-assessment strategies promises potential
      benefits for dental hygienists and the public they serve.

PMID- 11314479
TI  - Behavioral management instruction of anxious clients in the dental hygiene
      curricula.
AB  - PURPOSE: This study sought to determine the type and amount of instruction on
      behavioral management of anxious clients in dental hygiene curricula, the
      instructional differences between associate and baccalaureate programs, and the
      opinions of educators regarding behavioral management. METHODS: A 19-item
      questionnaire was mailed to the directors of 210 dental hygiene programs who were
      asked to furnish information pertaining to behavioral instruction in their
      curricula and to express their opinions by use of a Likert scale. Data were
      analyzed using descriptive statistics and the chi-square and Z hypothesis tests.
      RESULTS: Two mailings resulted in an overall response rate of 81%, with 170
      questionnaires returned. Results revealed that 86% of programs surveyed taught
      behavioral management of anxious clients to their students. Types of strategies
      taught and percentage of programs teaching them were: information provision
      (96%), distraction (51%), modeling (51%), relaxation (62%), and hypnosis (7%). No
      significant relationships were found between associate and baccalaureate degree
      programs relating to the type of behavioral instruction; however, baccalaureate
      degree programs devoted significantly more curricular hours to this instruction.
      In general, the sample of dental hygiene educators held positive opinions
      regarding the use of behavioral management, with only 28% having had formal
      education in this area. CONCLUSION: Results suggest that comprehensive
      instruction on behavioral management of client anxiety is not provided to
      students in all dental hygiene programs, even though dental hygiene educators
      consider this modality effective during oral health care.

PMID- 11314480
TI  - Sexual harassment in dentistry: experiences of Virginia dental hygienists.
AB  - PURPOSE: The purpose of this study was to determine if dental hygienists in the
      Commonwealth of Virginia experienced sexual harassment while employed in oral
      health care settings. Other interests were to determine if dental hygienists
      experienced sexual harassment, to what extent they felt professionally prepared
      to respond to unwanted sexual behaviors; did they perceive sexual harassment as a
      problem in the oral health care environment; and was attrition from their
      employment associated with sexual harassment. METHODS: A questionnaire, Sexual
      Harassment in the Dental Hygiene Profession, designed by the author, was used in
      this research. A list of currently licensed and registered dental hygienists was
      obtained from the Virginia Board of Dental Examiners and the questionnaire was
      sent to 540 randomly selected registered Virginia dental hygienists. Two weeks
      after the initial mailing, a second questionnaire was sent to non-respondents.
      The survey elicited data on experience, management, and personal opinions
      relative to sexual harassment, as well as demographic information. Results were
      analyzed using frequencies, percentages, and the chi-square test of association.
      RESULTS: Two hundred eighty-five surveys (53%) were returned and useable.
      Findings revealed that 54% of the responding dental hygienists experienced sexual
      harassment. Of these, 50% experienced sexual harassment four or more years ago,
      23% one to three years ago and 28% within the last year; these categories were
      mutually exclusive. The perpetrators of the harassment were reported to be either
      male dentists (73%) or male clients (45%). Less than 10% reported being harassed
      by women. While 70% of the sexually harassed respondents indicated that filing
      formal complaints was an effective strategy for managing sexual harassment, less
      than 1% actually did so. Of all dental hygienists (harassed or not), 90% did not
      receive training in their dental education to manage sexual harassment, and 85%
      would like the American Dental Hygienists' Association to develop model
      guidelines and policies. Demographic characteristics were typical of practicing
      dental hygienists in Virginia; 99% female, 96% Caucasian, and 86% married with a
      mean age of 40 years. CONCLUSION: Information about managing sexual harassment
      needs to be incorporated into the dental hygiene curricula. This curriculum
      addition should include information on identifying sexual harassment incidents,
      strategies for controlling unacceptable behavior, the legal rights of employees,
      and the process of filing a formal complaint. Dental hygienists need to identify
      sexual harassment behaviors and receive prevention training though continuing
      education courses. Furthermore, the American Dental Hygienists Association and
      the American Dental Association need to collaboratively develop guidelines and
      policies for dentists and dental hygienists regarding the management of sexual
      harassment in the oral health care setting.

PMID- 11314481
TI  - Adequacy of dental records in clinical practice: a survey of dentists.
AB  - PURPOSE: The purposes of the study were to determine Minnesota dentists'
      perception of the adequacy of their dental record documentation, assess the
      general format and contents of dental records they used, and compare the self
      reported contents of dental records with guidelines established by the American
      Dental Association (ADA). METHOD: Using ADA's published recommendations for
      structure and guidelines of the dental record from 1987, a 20-item questionnaire
      was developed, pretested, and used to survey a random sample of 750 Minnesota
      dentists. Reminder postcards were sent two weeks after the initial survey
      mailing. A third mailing to nonrespondents, including cover letter and duplicate
      questionnaire, was conducted three weeks later. Of the surveys returned, 63% (N =
      475) were analyzed. Data analyses, including frequencies and tests of chi-square,
      were conducted using Statview and SPSS. RESULTS: While 15% (N = 69) of
      respondents used a single-page record format, 44% (N = 209) used multiple forms
      filed in a specific location within the record. Of the dentists responding, 403
      (85%) felt their record documentation was adequate without comparison to any
      specified criteria. However, statistically significant differences occurred
      between dentists' perception of record adequacy and the actual presence or
      absence of ADA criteria for all record components. Data analysis revealed that
      information was absent 9.4% to 87.1% of the time. CONCLUSION: A discrepancy
      exists between dentists' perception of dental record adequacy and the ADA
      recommendations for structure and guidelines. Inadequate dental record components
      should be targeted for improvement.

PMID- 11314482
TI  - Ten years of patients' experiences with fixed implant-supported prostheses.
AB  - PURPOSE: This study investigated patients' perceptions of fixed implant-supported
      prostheses (ISP) in totally edentulous jaws in order to obtain a broader base for
      patient information. METHODS: A total of 135 patients who had received prosthetic
      rehabilitation treatment responded to a questionnaire on oral functions, speech,
      oral self-care, esthetics, lifestyle changes and self-confidence, oral comfort,
      and overall satisfaction with ISP. The patients also listed positive and negative
      experiences with the ISP. RESULTS: Most patients (97%) reported overall
      satisfaction. Chewing ability was rated as good or very good by all but one
      (99.3%). Twenty-six patients (19.6%) identified bruxing and clenching habits;
      there were significantly younger than those free from problems. Phonetic problems
      were reported by 32.8% after insertion, with 18.6% (eight patients) having
      remaining problems after seven to 10 years. Most of the patients (87.2%) found it
      easy to clean the prosthesis. Improved lifestyle after ISP insertion was reported
      by 75% and increased self-confidence by 82% of the patients. Improvements were
      especially perceptible in social situations that involved conversation or eating.
      None of the measured variables was related to duration of having ISP.
      CONCLUSIONS: The patients' experiences in this study lasted over a period of 10
      years, thus their positive and negative aspects can serve as information support
      for dentistry to enable future ISP patients to make appropriate choices. The
      information could be made available to patients by including in a patient
      targeted booklet.

PMID- 11314483
TI  - Uprighting molars with twisted superelastic nickel titanium wires.

PMID- 11314484
TI  - The crown bracket bonding system.

PMID- 11314485
TI  - A simple method of aligning maxillary second molars toward the end of treatment.

PMID- 11314486
TI  - Treatment of tooth impaction and transposition with a segmented-arch technique.

PMID- 11314487
TI  - Correction of anterior crossbite in the mixed dentition.

PMID- 11314488
TI  - Subdivision malocclusions: cracking the riddle.

PMID- 11314489
TI  - Another view from the top: the political race impact.

PMID- 11314490
TI  - Leukemia inhibitory factor enhances bone formation in calvarial bone defect.
AB  - For bone defect reconstruction, locally administered cytokine plasmid was
      examined. Leukemia inhibitory factor (LIF) can bind to the osteoblast cell
      surface and induce bone formation both in vitro and in vivo. The authors
      investigated the local mouse LIF complementary deoxyribonucleic acid (cDNA)
      plasmid in the pcDNA 3 expression vector, which is promoted by cytomegalovirus
      and is stabilized by bovine growth hormone polyadenylation, with a gelatin sponge
      carrier. A total of 150 male Wistar rats were used. They were divided into three
      groups. Group 1 (N = 30) was treated with the gelatin carrier of the pcDNA 3
      vector, group 2 (N = 90) was treated with three different doses of LIF cDNA (0.1,
      1, and 10 micrograms) in the pcDNA 3-vector plasmid along with the gelatin
      carrier, and group 3 (N = 30) was treated with recombinant human bone
      morphogenetic protein -2. Ten animals in each group were euthanized at 1, 3, and
      5 weeks postoperatively. Animals treated with LIF cDNA showed significantly
      enhanced bone mineral density (p < 0.05), as confirmed by dual-energy X-ray
      absorptiometry (DEXA), in 3 weeks compared with the control vehicle. By 3 weeks,
      the number of fibroblast-like cells and collagen fibers decreased, whereas the
      osteoblast-like cells increased inversely, as revealed during histological
      examination. LIF messenger ribonucleic acid demonstrated by in situ hybridization
      was observed most markedly in osteocytes of the LIF cDNA-treated group. Also, LIF
      peptide was detected in the same cell type by immunohistochemistry. Locally
      administered LIF cDNA plasmid in a gelatin carrier can increase bone density
      significantly, with subsequent bone formation, probably via osteocyte activation.

PMID- 11314491
TI  - Gene expression of transforming growth factor-beta 3 and tissue inhibitor of
      metalloproteinase type 1 during membranous bone healing in rats.
AB  - A number of growth factors have been implicated in fracture repair. Transforming
      growth factor-beta 3 (TGF-beta 3) is believed to be involved in osteoblast
      proliferation, chemotaxis, and collagen synthesis. The collagens act as the
      scaffolding for new bone matrix formation, whereas tissue inhibitors of
      metalloproteinases (TIMPs) may help regulate matrix remodeling in bone repair.
      Despite their hypothesized integral role in fracture repair, the temporal
      expression of these molecules in membranous bone fracture healing remains
      unknown. The objective of this study was to assess the temporal pattern of TGF
      beta 3 and TIMP type 1 (TIMP-1) expression in rat mandibular fracture healing.
      Twenty-eight adult male Sprague-Dawley rats underwent a mandibular osteotomy, and
      the healing regenerate was harvested on postoperative days 3, 5, 7, 9, 23, and
      37. Total cellular ribonucleic acid was isolated, and Northern analysis was
      performed. TGF-beta 3 expression was downregulated dramatically 3 days after the
      osteotomy and remained less than 20% of control levels throughout repair. In
      marked contrast, TIMP-1 gene expression, low during early repair, increased more
      than twofold over control at later time points. Understanding the temporal
      pattern of gene expression during membranous fracture healing has important
      clinical implications because elucidating these mechanisms may lead to
      appropriate biomolecular approaches to augment membranous bone fracture healing.

PMID- 11314492
TI  - Producing a full-scale model from computed tomographic data with the rapid
      prototyping technique using the binder jet method: a comparison with the laser
      lithography method using a dry skull.
AB  - Rapid prototyping using the binder jet method has recently been established and
      has already produced excellent results in industrial applications. The authors
      recently developed a technique for producing a full-scale model from computed
      tomographic (CT) data with the binder jet method as an approach to overcome the
      shortcomings of the laser lithography method, which is already widely used in
      medicine. They conducted a comparative investigation of full-scale models made
      with both techniques using a dry skull to determine the accuracy of the models.
      It was clearly demonstrated that the accuracy of the binder jet method was high
      enough to be used in craniomaxillofacial surgery because it was the same as the
      laser lithography method. This study employed data from the latest helical volume
      scan computed tomography device using a multidetector. The study showed that the
      new rapid prototyping technique was satisfactory in terms of speed, cost,
      installation environment, and accuracy of models, and that detailed shapes and
      structures can be reproduced well. Because this technique has many advantages
      over the laser lithography method, it should play a major role in
      craniomaxillofacial surgery and in other medical fields in combination with
      advances in CT devices. Although plaster is a more suitable fixation material
      when the emphasis is on the reproducibility of detailed structures, the binder
      jet method using starch is extremely useful for simulating operations and
      determining implant shapes because it allows for the prompt production of models.

PMID- 11314494
TI  - Chin augmentation with a bone graft from the mandibular region.
AB  - The prominent, square angles of the mandible are not generally considered an
      alluring virtue in Asian women because a square chin is thought to be masculine,
      and sunken cheeks are thought to be ill-fated. An oval, slender face is
      customarily preferred. A 28-year-old single woman requested reduction of the
      mandibular angle and concomitant chin augmentation. Each scalene triangular piece
      of the bone from both mandibular angles was carved and shaped like an obtuse
      triangle. One side of its surface was serrated to effect a curve, and the
      revision was fixed with a miniplate. The pieces were placed on top of each other,
      set on the symphysis menti, and were immobilized with screws. The excised
      fragments of the mandible were used as bone grafts to augment the chin during the
      same operation.

PMID- 11314493
TI  - Plasma-treated lenowoven polyethylene ribbon for bone fixation at dentoalveolar
      osteotomy.
AB  - Plasma-treated lenowoven polyethylene ribbon was used for splinting between teeth
      around osteotomy lines in anterior segmental dentoalveolar osteotomy. This
      fixation was continued for 2 to 3 months, during which there was no damage or
      fall of the ribbon. In addition, the patients were able to eat their usual food,
      had much less pain in the teeth and oral mucosa, did not feel uncomfortable in
      the mouth, had no tooth damage or carious teeth, and had a good aesthetic
      appearance. In all eight jaws (five patients), accurate and strong bone fixation
      was achieved based on the planned occlusion. Patient complaints and pain were
      obviously less with this method than other methods. Polyethylene ribbon is quite
      useful for bone fixation in anterior segmental dentoalveolar osteotomy.

PMID- 11314495
TI  - A theory on the embryogenesis of oculo-auriculo-vertebral (Goldenhar) syndrome.
AB  - Oculo-auriculo-vertebral (OAV) syndrome is made up of anomalies, mainly of first
      and second branchial arch derivatives. Characteristic features include structural
      malformations of the external and middle ears, face, and jaw. It has been
      previously suggested that hemorrhage involving the first and second branchial
      arches causes hypoplasia and malformation of the face and auricle, but this
      theory cannot explain the multisystemic and protean manifestations of this
      disease. The theory set forth describes the cutaneous, facial, vertebral, and
      systemic anomalies in the OAV spectrum as a result of ectodermal nondisjunction
      early in development with subsequent mesodermal tethering. A subgroup of OAV may
      therefore be a disorder of ectodermal nondisjunction involving the otic placode
      similar to the spectrum of diseases such as occult spinal dysraphism that is
      associated with the same mechanism in the embryonic neuraxis. This would imply a
      molecular mechanism involving cell adhesion molecules that unify the two disease
      processes and explain the multisystem anomalies of the OAV syndrome.

PMID- 11314496
TI  - Regeneration of the sagittal suture by GTR and its impact on growth of the
      cranial vault.
AB  - The aim of this study was to investigate the effect of bone grafting, suture
      transplantation, and guided tissue regeneration (GTR) treatment on healing of
      craniectomy defects involving the sagittal cranial suture and on the growth of
      the cranial vault. Fifty 4-week-old rats were included in the study. A 5.0 mm
      wide trephine defect was created with its midline corresponding to the sagittal
      cranial suture between the coronal and occipital cranial vault sutures. The
      animals were randomly allocated to five groups of 10 animals. Group A: The
      cranial defect was left untreated. Group B: An occipital bone graft was placed
      into the cranial defect. Group C: A cranial bone graft including a portion of the
      frontal suture was placed in the cranial defect. Group D: The cerebral and galeal
      aspect of the defect were covered with an e-PTFE membrane. Group E: The animals
      were sham-operated, no defect was created. In all animals, two gutta-percha
      points were placed demarcating the lateral borders of the parietal bones.
      Histological analysis at 4 months following surgery showed that the untreated
      cranial defects healed with fibrous connective tissue. The bone-grafted defects
      healed partially with bone and connective tissue in the periphery of the bone
      graft. The healing of suture-grafted defects resembled that of the bone-grafted
      defects, since the transplanted suture became completely obliterated with bone.
      The membrane-treated defects healed with bone and a suture-like tissue resembling
      the sagittal suture of the sham-operated controls. Cephalometric measurements
      demonstrated that membrane-treated and sham-operated control animals exhibited
      significantly more (P < 0.05) coronal growth (approximately 1.2 mm) than that of
      the remaining three groups of animals (approximately 0.7 mm). These findings were
      supported by the craniometry measurements demonstrating that sham-operated
      control and membrane-treated specimens presented significantly more cranial width
      than that of the remaining groups of animals (P < 0.05). It can be concluded that
      complete osseous healing, creation of a new sagittal suture, and increased
      cranial growth can be achieved by the treatment of craniectomy defects with the
      GTR technique.

PMID- 11314497
TI  - Approaches to cleft lip and palate repair.
AB  - Facial clefts remain one of the most common congenital anomalies encountered by
      plastic surgeons. Over the last few decades, surgical results have continued to
      improve due to the interdisciplinary approach to this complex clinical problem.

PMID- 11314499
TI  - Resorbable polymer fixation for craniomaxillofacial surgery: development and
      engineering paradigms.
AB  - Advances in medical technology continue to present clinicians with new treatment
      options for their patients. Frequently, however, a "settling-in" period occurs
      after initial introduction, during which continued use and experience present new
      considerations. Absorbable internal fixation has been available in the orthopedic
      arena for more than a decade, but has been widely available in the
      craniomaxillofacial arena for only the past few years. Although the major
      considerations governing its use were obvious initially, since then a set of
      essential paradigms has presented itself. The authors summarize these principles,
      providing numerous clinical examples, with the goal of illustrating the current
      potential of this technology as well as establishing a baseline from which future
      developments can issue.

PMID- 11314498
TI  - Helmet versus nonhelmet treatment in nonsynostotic positional posterior
      plagiocephaly.
AB  - A total of 105 infants with nonsynostotic posterior plagiocephaly were treated
      using a helmet or by head positioning. Effect of treatment was scored using a
      cosmetic outcome score (0-10 points) assigned by the parents. The onset of the
      observed skull deformity correction was not different for the helmet vs.
      nonhelmet treatment. Improvement was significantly better and faster in the
      helmet group compared with nonhelmet treatment (p < 0.01 and p < 0.001,
      respectively).

PMID- 11314500
TI  - Assessment of the relationships among posture, maxillomandibular denture complex,
      and soft-tissue profile of aesthetic adult Korean women.
AB  - The objective of this study was to assess the relationships among the posture,
      the maxillomandibular denture complex, and the soft-tissue profile of aesthetic
      adult Korean women. From an initial group of 346 women, the authors examined 28
      beautiful adult Korean women who had normal vertical and sagittal skeletal
      relationships and normal occlusion. There were no differences in the inclinations
      of the incisors to the occlusal planes in the maxilla and the mandible in the
      data for Korean women vs. Arnett's data for white women. However, the overbite
      and overjet in Korean women were slightly smaller than in white women. AB to
      maxillary occlusal plane angle (MxOP) represented the anteroposterior denture
      base discrepancy to the occlusal plane. Angulation of the maxillary occlusal
      plane to the Frankfurt (FH) plane and the true vertical line at submasale (TVL)
      (Sn) was a little steeper in Korean women than in white women. The FH plane was
      almost parallel to the true horizontal line in Korean women who had normal
      vertical and sagittal skeletal relationships and normal occlusion. With regard to
      soft-tissue variables, the upper lip length (Sn-Stms), interlabial gap, upper
      incisor exposure, nasolabial angle, lip and nose tip projection value, and TVL
      (Sn)-to-upper lip line (UL) angle showed interracial differences. The results of
      this study can assist in the diagnosis and treatment planning of orthognathic
      surgery.

PMID- 11314501
TI  - Political activism and professionalism.

PMID- 11314502
TI  - Community dental health care.

PMID- 11314503
TI  - Dental education. Setting the standard for dental education.

PMID- 11314505
TI  - General dentistry.

PMID- 11314504
TI  - Dental research. Riding the "Crest" of dental research.

PMID- 11314506
TI  - Dentistry specialties.

PMID- 11314507
TI  - Community dental health.

PMID- 11314509
TI  - Infection control in the twenty-first century.

PMID- 11314508
TI  - Dental radiology.

PMID- 11314510
TI  - Dental materials and technology.

PMID- 11314511
TI  - Dental benefits.

PMID- 11314512
TI  - Dental education: a glimpse of the future.

PMID- 11314513
TI  - Peri-implant mucosal inflammation and bone loss: clinical and radiographic
      evaluation of 108 dental implants after 1-year loading.
AB  - OBJECTIVE: To evaluate the clinical outcomes, and a possible correlation between
      peri-implant mucosal inflammation and marginal bone loss, 1 year after
      restoration in a group of Chinese patients with dental implants. METHODS:
      Observation of the clinical and radiographic parameters of 108 IMZ and Frialit-2
      dental implants in 70 patients. RESULTS: One year after loading, there were no
      signs of mobility and peri-implant radiolucency in any of the implants. The
      average bone loss adjacent to implants was 0.63 mm (SD 0.78). The prevalence of
      peri-implant mucosal inflammation, as indicated by sulcus bleeding index (SBI) of
      1.0 or more, was 32.9%. Significant positive correlation was found between
      mucosal inflammation and bone loss (P < 0.05). 92% of the observed sites had
      plaque index (PLI) scores greater than 1. CONCLUSIONS: The 1-year outcomes from
      this patient group indicate that IMZ and Frialit-2 implants provide satisfactory
      clinical results. One of the etiologic factors of alveolar bone loss around
      implants seems to be plaque-associated marginal inflammation. Improvement of oral
      hygiene, elimination of soft tissue inflammation, and proper treatment of
      periodontal disease of natural teeth are critical for maintaining the implants.

PMID- 11314514
TI  - In situ hybridization analysis of transforming growth factor-beta 1 RNA
      expression during mouse tooth development.
AB  - OBJECTIVE: The aim of this study is to investigate the temporal and spatial
      expression and localization of transforming growth factor-beta 1 mRNA during
      mouse tooth development. METHODS: The distribution pattern of TGF-beta 1 mRNA
      during tooth development was analyzed on 5 microns serial sections of
      paraformaldehyde-fixed and paraffin-embedded embryonic mouse heads or mandibles.
      RESULTS: The results show that TGF-beta 1 mRNA is expressed during mouse tooth
      development in a temporally and spatially regulated fashion. Local expression of
      TGF-beta 1 mRNA in the dental epithelium at budstaged (E13) and capstaged (E15)
      teeth were observed. During bell stage (E16-18), TGF beta 1 mRNA was very
      abundant in the ameloblast layer and dental papilla cells. The expression of TGF
      beta 1 increased in the layer of odontoblast and ameloblast with the
      differentiation of these cells. CONCLUSION: These results suggest that TGF-beta 1
      may have an important role in odontogenesis and that it acts as a paracrine and
      autoinducing factor.

PMID- 11314515
TI  - Apoptosis of osteoclast-like cells induced by alendronate is related to Fas gene
      expression.
AB  - OBJECTIVE: To detect the mechanism of alendronate during inhibition of bone
      resorption by inducing apoptosis of osteoclasts and its relationship with the Fas
      gene. METHODS: The osteoclast-like cells (OCLs) from a giant cell tumor in vitro
      were used. After treatment with alendronate for 48 hours, the OCLs were
      identified by fluorescence microscope, transmission electron microscope, in situ
      end labeling (TUNEL), HE staining, in situ hybridization with Dig-Fas Probe, and
      immunohistochemistry with anti-Fas antibodies. RESULTS: The detachment rate of
      OCLs was 76% after exposure to alendronate, while the control cell detachment
      rate was only 3%. The nonadherent OCLs showed the features of cell contraction,
      pyknosis, chromatin condensation connecting with nuclear membrane to form circle
      or crescent bodies, and occasional nuclear fragmentation. The detached OCLs were
      positive by in situ end labeling, and the control group was negative. Nonadherent
      OCLs were ultrastructurally consistent with apoptosis (shrunken cells with
      pyknotic nuclei, chromatin condensation connecting with nuclear membrane,
      mitochondria recruitment with intact structure, and loosening of endoplasmic
      reticulum). The results by in situ hybridization and immunohistochemistry
      indicated that the Fas gene expression of nonadherent OCLs were positive, but the
      controls were negative. CONCLUSION: Alendronate promotes apoptosis of the OCLs
      and it is related with the expression of the Fas gene.

PMID- 11314516
TI  - Influence of amalgam on the growth of mutans streptococcus: an in vivo study.
AB  - OBJECTIVE: To study the antibacterial activity of dental amalgam against mutans
      streptococcus. METHODS: Study volunteers included 14 patients, 21 to 35 years
      old, with aged amalgam fillings, with no antibiotic use during the previous 3
      months, and 16 patients, 22 to 24 years of age, without aged amalgams, but with
      unfilled caries. Plaque samples were collected once from the subjects with aged
      amalgams. Subjects with fresh amalgams had plaque samples collected at 1 day, 1
      week, 2 weeks, 4 weeks, and 8 weeks after amalgam restoration. As controls,
      plaque samples were collected from unrestored occlusal enamel surfaces on the
      same side, or on the opposite side of the same occlusion. Frequency of mutans
      streptococci from aged amalgams and fresh amalgams and the colony-forming units
      (CFU) were tested. RESULTS: The difference of CFU of mutans streptococci in the
      plaque samples between the amalgam restorations, the aged amalgams, and the
      controls was not significant within 8 weeks after amalgam filling. The difference
      of CFU of mutans streptococci in plaque samples from the amalgam restorations
      between all the timepoints was significant except between the fourth week and
      eighth week. For the control group, however, the difference in values between the
      first day and the timepoints afterward were significant, except between the first
      day and the first week. The difference between the first week and later
      timepoints was significant, but not between the second week and later, or between
      the fourth week and later. At the eighth week, the difference between the aged
      amalgam and controls was not significant. CONCLUSION: Amalgam had some inhibitory
      effect on the in vivo growth of mutans streptococci.

PMID- 11314517
TI  - Immunohistochemistry of bone sialoprotein and osteopontin during reparative
      dentinogenesis in vivo.
AB  - OBJECTIVE: To investigate the stage-specific and tissue expression of bone
      sialoprotein (BSP) and osteopontin (OPN) during reparative dentinogenesis in
      vivo. METHODS: Direct pulp-capping with Ca(OH)2 developed a model used for the
      investigation of reparative dentinogenesis in the exposed dental pulp. In this
      model, standardized class V cavities were prepared close to the gingival margin
      on the buccal surface of each tooth. Animals were sacrificed 3, 7, and 10 days
      post-operation. Immunohistochemical staining determined the tissue-specific
      expression of BSP and OPN during the process. RESULTS: Odontoblast-like cells and
      reparative dentin reacted positively with BSP and OPN. The expression of BSP
      reached a peak at day 7, then gradually decreased, while the expression of OPN
      showed no significant difference between day 7 and day 10. CONCLUSION: BSP and
      OPN may play different roles in reparative dentinogenesis. BSP may serve as a
      nucleator of hydroxyapatite crystal formation.

PMID- 11314518
TI  - A study of oral health condition in individuals with no oral hygiene and its
      association with plaque acidogenesis.
AB  - OBJECTIVE: To study the association of long-term deposited plaque, due to lack of
      oral hygiene, with acidogenesis of the plaque bacteria. METHODS: Seventy-seven
      subjects with poor oral hygiene were selected. Debris index (DI) and calculus
      index (CI) were recorded. Among them, 16 were DMFS > 8, and comprised the caries
      active (CA) group; 27 were caries free, and comprised the caries free (CF) group.
      Plaque fluids in both groups were analyzed for organic acids, phosphate, and
      inorganic cations by use of capillary electrophoresis, while pH was measured by
      microelectrodes. RESULTS: No differences were found on debris index (CF group
      measured 2.07-0.47, CA group measured 2.01-0.53) or calculus index (CF group
      measured 2.47-0.50, CA group measured 2.48-0.53) relative to carious status,
      although there was a positive relationship between DI and CI (r = 0.52, P <
      0.001). The main finding in this study was that the quantity of lactic acid
      produced by sucrose exposure in these individuals with poor oral hygiene was much
      less (increased no more than 2 times, compared with content at rest) than in a
      previous report (increased 3 to 5 times, compared with content at rest) on
      subjects with good oral hygiene habits. CONCLUSIONS: Long-term deposited plaque
      due to lack of oral hygiene may have less cariogenic capability, although
      patients' susceptibility to periodontal disease would increase.

PMID- 11314519
TI  - Characterizations of three surface-modified titanium oxide films.
AB  - OBJECTIVE: To seek a new method of titanium passive treatment by combined anodic
      oxidation and thermal air treatment, which could increase the corrosion
      resistance and biocompatibility of pure titanium. MATERIAL AND METHODS:
      Characteristics of Titanium sheets with natural oxide film (NOF), anodic oxide
      film (AOF), or heated anodic oxide film (HAOF) were compared and tested by x-ray
      diffractrometer, electrochemical corrosive method, and contact angle device.
      RESULTS: HAOF had excellent corrosion resistance and greater crystallinity,
      indicating the crystal structure had changed. AOF had better hydrophily.
      CONCLUSION: This in vitro study showed that thermal air treatment, after anodic
      oxidation, was a reliable method for creating a passive, protective film on the
      titanium surface, which could greatly enhance the corrosion-resistance and
      crystallinity.

PMID- 11314520
TI  - Experimental study of anterior disc displacement in the rabbit temporomandibular
      joint.
AB  - OBJECTIVE: To create an animal model of anterior disc displacement of
      temporomandibular joint (TMJ) for studying the pathologic change of anterior disc
      displacement. METHODS: The disc was surgically displaced anteriorly in the right
      temporomandibular joint in each of 25 rabbits. The outer capsular of anterior
      attachment of disc was exposed through the floor of the orbit and the temporal
      extension of the anterior band of disc was sutured to the zygomatic arch. The
      left side was approached in a similar manner except for repositioning the disc
      anteriorly. Five additional rabbits served as non-surgical controls. The animals
      were sacrificed at 1, 2, 4, 8, and 12 weeks after surgery. The histological
      changes were observed. RESULTS: Microscopic observation showed 11 joints with
      partial anterior disc displacement, 8 joints with complete anterior disc
      displacement, and 6 joints with perforation of disc in the surgical groups. The
      histological changes included physiologic remodeling or early degenerative
      changes in the partial anterior disc displacement joints, degenerative changes in
      the complete disc displacement joints, and severe osteoarthritic changes in the
      perforated joints. CONCLUSION: The degree of anterior disc displacement caused
      different kinds of osteoarthritic changes in the articular cartilage of the
      experimental animals.

PMID- 11314521
TI  - Abnormalities of the human Rb tumor suppressor gene in oral squamous cell
      carcinoma.
AB  - OBJECTIVE: To investigate the status of Retinoblastoma (Rb) gene in 30 patients
      with primary oral squamous cell carcinoma (OSCC) and 3 healthy control samples.
      MATERIAL AND METHODS: We determined the status of Rb tumor suppressor gene in
      oral squamous cell carcinoma using a DNA southern blotting assay with Digoxin
      (Dig) labeled Rb cDNA probe. RESULTS: The structural abnormalities of Rb tumor
      suppressor gene were detected in 8 of the 30 invasive OSCC samples analyzed
      (8/30). 7 cases contained partial gene deletion, and there was 1 case of gene
      rearrangement. The structural abnormality rate of Rb is 26.7%. No correlation was
      found between the alteration of Rb gene with the sex, age, site of primary tumor,
      level of histopathological differentiation, and TNM staging. CONCLUSIONS: Our
      study shows that abnormalities of the Rb tumor suppressor gene occur in oral
      squamous cell carcinoma, which include Rb deletion and Rb rearrangement, but its
      abnormality rate is low.

PMID- 11314522
TI  - Effect of lactoperoxidase system on glucosyltransferase D of Streptococcus
      mutans.
AB  - OBJECTIVE: To investigate the effects of the peroxidase system (LP, H2O2, SCN)
      and its components on the activity of glucosyltransferase D (GtfD) originating
      from Streptococcus mutans (S. mutans). METHODS: GtfD was incubated in buffered
      KCl assay mixture that contained 20 microM dextran and 100 mM sucrose including
      14C-glucose. The activity of GtfD was measured with a scintillation counter. The
      effects of lactoperoxidase system and its components on GtfD activity were
      examined by incubating different components separately and together with GtfD.
      RESULTS: The lactoperoxidase system-generated hypothiocyanite (OSCN) had no
      effect on the activity of streptococcal GtfD, while the lactoperoxidase enzyme
      inhibited GtfD. The ratio between the 2 enzymes, LP and GtfD, was important for
      the inhibition. However, if LP was combined with its substrates, SCN and/or a
      high concentration of H2O2, it enhanced the activity of GtfD. CONCLUSION:
      Peroxidase-generated antimicrobial agent HOSCN/OSCN is not inhibitory against
      GtfD, whereas low concentrations of the LP-enzyme inhibit GtfD.

PMID- 11314523
TI  - Acidogenicity and acidurance of fluoride-resistant Streptococcus sobrinus in
      vitro.
AB  - OBJECTIVE: To induce fluoride-resistant mutants of Streptococcus sobrinus in
      vitro and to study the acidogenic and acid tolerance of fluoride-resistant
      strains. METHODS: Fluoride-resistant mutants 6715-FR and S1-FR were obtained by
      subculturing S. sobrinus 6715 and freshly isolated S. sobrinus SSMU-S1 to media
      TSA or TSB, which contained different concentrations of fluoride. The lactic
      production and growth of fluoride-resistant strains and their respective parent
      strains were measured by gas chromatography and ultra-violet visible
      spectrophotometer. RESULTS: The stable fluoride-resistant mutants of S. sobrinus
      had been induced successfully in vitro. The acid production of 6715-FR or S1-FR
      was significantly greater than their parent strains in the presence of 0.5 or 5.0
      mM fluoride. In the absence of fluoride, there were 2 situations: The lactic
      production of F-resistant S. sobrinus was less than or equal to its parent
      strains when initial pH value was above 5.0 while the result was the opposite
      when pH value was below 5.0. The F-resistant strains and the parent strains of S.
      sobrinus could reduce the suspension pH to identical values in the absence of
      fluoride, and the F-resistant strains were more aciduric in the presence of
      fluoride. CONCLUSIONS: The F-resistant strains of S. sobrinus had higher
      acidogenic and aciduric ability than the wild-type strains, and were expected to
      have stronger cariogenic potential at plaque fluoride levels.

PMID- 11314524
TI  - Facilitation of midline correction with a premolar extraction sequence.

PMID- 11314525
TI  - Mandibular protraction appliance IV.

PMID- 11314526
TI  - An expedited indirect bonding technique.

PMID- 11314527
TI  - Laboratory and clinical evaluation of a self-etching primer.

PMID- 11314528
TI  - The straight-wire concept in lingual orthodontics.

PMID- 11314529
TI  - Triangular wire.

PMID- 11314530
TI  - Factors related to the efficacy of an adjustable oral appliance for the treatment
      of obstructive sleep apnea.
AB  - AIM: The purpose of this study was to investigate whether any physiological or
      cephalometric parameters could be used to predict the efficacy of the Klearway
      oral appliance (OA) for the treatment of obstructive sleep apnea (OSA). METHODS:
      Forty-two male and 5 female patients with OSA were recruited on the basis of
      baseline polysomnography with a documented Apnea and Hypopnea Index (AHI) > 15
      per hour. Repeat polysomnography was performed with the appliance in place.
      Baseline cephalometry was performed for each patient. Subjects were divided into
      3 groups on the basis of the degree of change in AHI with OA therapy: good
      response (> 75% decrease in AHI), moderate response (25% to 75% decrease range in
      AHI), and poor response (< 25% decrease in AHI). RESULTS: Patients with a good
      response were younger and had smaller upper airways. A stepwise regression
      analysis revealed that a better treatment response with the Klearway appliance
      was obtained in patients who were younger and had a lower body mass index, a
      longer maxilla, a smaller oropharynx, a smaller overjet, less erupted maxillary
      molars, and larger ratio of vertical airway length to the cross-sectional area of
      the soft palate.

PMID- 11314531
TI  - Chondrocyte allografts for repair of full-thickness defects in the condylar
      articular cartilage of rabbits.
AB  - PURPOSE: This study investigated the feasibility of repairing defects of the
      condylar articular cartilage by chondrocyte allotransplantation. MATERIAL AND
      METHODS: A full-thickness defect (2 mm diameter) was made in the condylar
      articular cartilage of 6-month-old rabbits with a No. 701 dental fissure bur that
      penetrated both the articular cartilage and the subchondral bone, and entered the
      marrow cavity. Sixty-four animals were divided into 5 groups. In the cell
      transplantation group (20 rabbits), the defect was filled with a collagen
      membrane embedded with chondrocytes of neonate rabbits cultured in vitro for 1
      week. In control group 1 (18 rabbits), the defect was left untreated. In control
      group 2 (18 rabbits), the defect was filled with a collagen membrane without
      chondrocytes. In sham-operation control group (6 rabbits), the condyle surface
      was exposed but left unchanged. Two rabbits were added as a normal control group.
      Mandibular movement was not restricted postoperatively. The macroscopic and
      microscopic features of the condyles were observed at 1, 2, 4, 8, 12, and 20
      weeks following surgery. RESULTS: The defects in the condylar articular cartilage
      were repaired with cartilage tissue after cell transplantation. CONCLUSION: A
      defect in the condylar articular cartilage can be repaired with articular
      cartilage-like tissue by allotransplantation of chondrocytes.

PMID- 11314532
TI  - Distribution of substance P-like immunoreactive fibers in feline
      temporomandibular joint.
AB  - OBJECTIVE: To study the distribution of substance P-like immunoreactive fibers in
      feline temporomandibular joint. METHODS: The immunohistochemical PAP method was
      used for the investigation of the distribution of substance P-like immunoreactive
      fibers in feline temporomandibular joint. RESULTS: The TMJ capsule and the
      anterior and posterior disc attachments all contained SP-immunoreactive nerve
      fibers, but the medium fibers in diameter were mainly observed. The density of
      the distribution of SP-positive nerve fibers was the highest in the subsynovium
      of the TMJ capsule. The density of distribution was similar in the anterior and
      posterior disc attachments, but lower than in the subsynovium and the lateral
      joint capsule. Such fibers in the synovial membrane were sparser, and a part of
      the fibers were seen around the thin blood vessels in all the foregoing tissues.
      CONCLUSION: These results provide the morphological data for exploring the
      neurobiological mechanisms of temporomandibular joint disorder and its pain.

PMID- 11314533
TI  - The expression of E-cadherin-catenin complex in adenoid cystic carcinoma of
      salivary glands.
AB  - OBJECTIVE: The aim of this study was to investigate the expression of the E
      cadherin-catenin (E-cad-cat) complex in human salivary adenoid cystic carcinoma
      (ACC) and determine the effects of E-cad-cat expression on tumor differentiation,
      metastasis, and invasion, as well as its clinical significance. METHODS: The
      expression of adhesion molecules, which included E-cadherin, alpha-catenin, and
      beta-catenin, on 10 cases of normal salivary glands, and 50 cases of human
      salivary ACC were investigated by immunohistochemistry. RESULTS: Strong and
      stable expression of E-cad-cat complex showed in normal salivary glands tissues.
      However, weaker expression and even complete absence, of the positive signals
      were shown on all ACC cases. Coexpression of E-cad-cat were detected in 29 (58%)
      of the 50 ACC specimens. Positive staining of E-cad-cat complex were detected in
      7 (39%) of the 18 ACC primary sites that had aggressive phenotype of nerve and
      vasculature. CONCLUSION: Strong positive signals of E-cad-cat complex are shown
      in normal salivary glands, and the down-regulated expression were observed in ACC
      cases. The expression of E-cad-cat complex is associated with a more aggressive
      phenotype on nerve and vasculature. No association with various histopathologic
      subtypes was found. However, absent or low E-cad expression was observed more
      frequently in solid carcinomas than in cribriform or tubular carcinomas. Down
      regulation of E-cad-cat complex may be associated with canceration of normal
      salivary glands. The expression levels of E-cad-cat were positively correlated to
      the differentiation of ACC tumor cells.

PMID- 11314534
TI  - Expression of cell cycle-associated proteins CDK4, p27, and E2F-1 in
      chondrosarcoma of the jaws.
AB  - OBJECTIVE: To elucidate the expression and significance of cell cycle-associated
      proteins in chondrosarcoma of the jaws. METHODS: CDK4, p27, and E2F-1 expression
      were examined in chondrosarcoma and osteochondroma of the jaws by
      immunohistochemical ABC method. RESULTS: CDK4, p27, and E2F-1 were positive in
      60% (12 of 20), 25% (5 of 20), and 65% (13 of 20), respectively, in
      chondrosarcoma of the jaws. There was no significant difference in the expression
      of CDK4, P27, and E2F-1 among histological grade of the chondrosarcoma (P >
      0.05). In osteochondroma of the jaws, CDK4 and E2F-1 showed an equal positivity
      of 12.5% (1 of 8), whereas p27 was positive in 87.5% (7 of 8). The positive rate
      of CDK4, p27, and E2F-1 was significant between chondrosarcoma and osteochondroma
      of the jaws (P < 0.05). CONCLUSION: These data show that cell cycle regulatory
      proteins are altered in chondrosarcoma of the jaws. CDK4 and E2F-1 are over
      expressed and p27 is under-expressed in chondrosarcoma of the jaws.

PMID- 11314535
TI  - Human papillomavirus infection and p53 alteration in oral squamous cell
      carcinoma.
AB  - OBJECTIVE: The aim of this study was to examine human papillomavirus 16/18
      infection incidence and p53 alteration in oral squamous cell carcinoma and to
      determine whether a correlation existed between HPV infection incidence and p53
      alteration in this disease. METHODS: A series of 60 oral tissues (40 oral
      squamous cell carcinomas, 20 normal oral mucosas) was studied by polymerase chain
      reaction (PCR) to detect HPV 16 and 18 infection, and was studied by single
      strand conformation polymorphism (SSCP) and immunohistochemistry (IHC) to detect
      p53 mutation and accumulation, respectively. RESULTS: HPV sequences were detected
      in 29 of 40 (72.5%) tumor specimens. A higher incidence (P = 0.037) of HPV 16/18
      infection was observed in oral squamous cell carcinomas than in normal oral
      mucosas. Altered p53, either in genetic sequence or protein overexpression, was
      observed in 18 of 40 (45%) oral squamous cell carcinomas. Eleven of the 29 HPV
      positive tumors contained observed alterations in either p53 protein expression
      or DNA sequence. No significant correlation (P = 0.145) was observed between HPV
      infection and p53 alteration. CONCLUSIONS: These data suggest that HPV16/18
      infection and/or p53 alterations are associated with oral squamous cell
      carcinoma. No inverse correlation exists between oncogenic HPV infection and p53
      alteration.

PMID- 11314536
TI  - Immunolocalization of heat shock protein 70 during reparative dentinogenesis.
AB  - OBJECTIVE: To investigate the immunolocalization of heat shock protein 70 (hsp
      70) during reparative formation and to discuss the role of heat shock response in
      dental pulp injury and repair. METHODS: A single cavity was prepared in the
      mesial surface of the first molars of both maxilla and mandible in Wistar rat.
      The animals were sacrificed at 3, 15, and 30 days post-operation. After the
      histological process, the paraffin sections were reacted with monoclonal
      antibodies against rat hsp 70 using the strept-avidin-biotin-peroxidase complex
      method. RESULTS: Immunolocalization demonstrated heavy staining for hsp 70 in
      normal pulp and at different stages of dental pulp repair. In normal pulp,
      immunoreactivity was visualized in the odontoblasts and the pulp fibroblast. In
      the group sacrificed at 3 days, heavy staining was located in the odontoblast
      process and cytoplasm. After 15 days, the newly formed odontoblast-like cells
      were strongly stained. At 30 days, the same staining intensity was observed in
      odontoblast-like cells and in pulp cells. No staining was seen in reparative
      dentin. CONCLUSION: These results demonstrated that heat shock protein 70 might
      play an important role as a molecular chaperone during reparative dentin
      formation.

PMID- 11314537
TI  - Leukoplakia and angiopoiesis resistance of Herba Erigerontis.
AB  - OBJECTIVE: To evaluate the effects of Herba Erigerontis on angiopoiesis and
      carcinogenesis; to seek an effective drug for prevention of leukoplakia
      progression to carcinoma and to stop the mechanism of angiopoiesis. METHODS:
      Carcinomatous conversions of golden hamster cheek pouches induced by Salley way
      and inhibited by Herba Erigerontis. Ink perfusion, analysis of images, resin cast
      form of micro-vessel, a-SMA detection and histopathological examination were
      applied to observe their changing patterns. RESULTS: The rate of leukoplakia
      conversion to tumor of the Herba Erigerontis group was half that of model group.
      The proportion of normal cells was approximately 4 times greater than that of
      model. The a-SMA levels of the Herba Erigerontis treated group was higher than
      that of model (P < 0.001). There was no significant difference between angeion
      vessel area and density (P > 0.05) in these 2 groups, which were elevated
      compared to the control. Nevertheless, the resin casts of the microvasculature in
      the Herba Erigerontis group showed that its configuration and spatial arrangement
      was similar to the control group. CONCLUSIONS: Herba Erigerontis has the function
      of inhibiting leukoplakia progression to tumor. This may be due to its ability to
      upregulate the expression of a-SMA. It has no obvious effect on angio-hyperplasia
      and expansion in the course of leukoplakia progression to tumor. However, it may
      preserve the angio-configuration and spatial arrangement and keep intact the
      angeion vessel wall. Its mechanism of promoting blood circulation may be through
      removing blood stasis and benign angiopoiesis so as to resist carcinogenesis.

PMID- 11314538
TI  - Clinical study of embolization of arteriovenous malformation in the oral and
      maxillofacial region.
AB  - OBJECTIVE: To evaluate the value of embolization on arteriovenous malformations
      (AVM) in the oral and maxillofacial region and to investigate the efficacy of
      several different embolic materials. CLINICAL MATERIALS AND METHODS: 10 cases
      with AVMs, including 5 AVMs mainly in the soft tissue and 5 intraosseous lesions,
      were embolized. Clinical and angiographic effects were analyzed during the 3 to
      16 months follow-up. RESULTS: In the 5 cases embolized without other treatment, 1
      case was embolized 3 times, 3 cases twice, and 1 case once. In these cases,
      postembolization angiograms revealed complete or nearly complete disappearance of
      the lesions. In the other 5 cases, embolized before surgery, intraoperative
      bleeding was significantly decreased. All these patients were free of recurrence
      during follow-up. Among the materials employed, NBCA seemed to offer a better
      result. CONCLUSIONS: Embolization may serve as the primary therapy for some AVMs
      in the oral and maxillofacial region, or as a routine preoperative adjunct for
      patients with severe intraosseous or disfiguring AVMs.

PMID- 11314539
TI  - The research and development of noncontact 3-D laser dental model measuring and
      analyzing system.
AB  - OBJECTIVE: To research and develop a new laser scanning 3-dimensional
      digitization system for collecting, showing, and measuring the data of dental
      casts. MATERIAL AND METHODS: According to the 3-dimensional measuring method, by
      using 2 pulsate motors to make the synthetic movement of the dental cast, a
      special semiconductor laser, and 2 special line array CCD, the 3-D data could be
      found anywhere on the surface of the dental cast. The program, developed with
      Visual C++ language under the Windows (Windows tm) system, can control the
      scanner, rebuild the 3-D graphics and measure the data of the dental cast.
      RESULTS: The system offers 70 x 70 x 70 mm measurement scope, 0.01 mm resoling
      power, < 0.1 mm mean deviation, and 25 mins for single cast scanning. CONCLUSION:
      The advantages of this system are its precision, simplicity, high efficiency, and
      wide range of measurements with complete direct view. This system also supplied
      new information that cannot be found with traditional measurement methods.

PMID- 11314540
TI  - Help yourself.

PMID- 11314541
TI  - Cantilever mechanics for treatment of impacted canines.

PMID- 11314542
TI  - Sectional ribbon archwire for pontic placement.

PMID- 11314543
TI  - Correction of single-tooth rotations with rotating springs.

PMID- 11314544
TI  - Transitional implants for orthodontic anchorage.

PMID- 11314545
TI  - Multidisciplinary treatment of an adult patient with a labiopalatal cleft.

PMID- 11314547
TI  - Dedicated sink for impression procedures.

PMID- 11314546
TI  - Tongue-friendly transpalatal arches.

PMID- 11314548
TI  - Attachment injuries in couple relationships: a new perspective on impasses in
      couples therapy.
AB  - This article identifies and operationalizes the newly defined construct of
      attachment injury. An attachment injury occurs when one partner violates the
      expectation that the other will offer comfort and caring in times of danger or
      distress. This incident becomes a clinically recurring theme and creates an
      impasse that blocks relationship repair in couples therapy. An attachment injury
      is characterized by an abandonment or by a betrayal of trust during a critical
      moment of need. The injurious incident defines the relationship as insecure and
      maintains relationship distress because it is continually used as a standard for
      the dependability of the offending partner. The concept of an attachment injury
      is defined here in the context of emotionally focused therapy, an empirically
      validated, short-term approach to modifying distress in couples. The broad
      theoretical underpinnings of this concept may be found in attachment theory as
      applied to adult romantic relationships. Through the delineation of attachment
      injury events and the ongoing development of a detailed model of resolution,
      couples therapists will be better able to identify, describe, and effectively
      treat such injuries and address the therapeutic impasses that are associated with
      them.

PMID- 11314549
TI  - Using eye movement desensitization and reprocessing to enhance treatment of
      couples.
AB  - Eye Movement Desensitization and Reprocessing (EMDR) as a clinical technique may
      enhance treatment effectiveness when applied within a couple therapy approach
      that is emotionally and experientially oriented. Clinical experience indicates
      that EMDR-based interventions are useful for accessing, activating, tolerating,
      and reprocessing the intense emotions that often fuel dysfunctional couple
      interactions. Using EMDR within conjoint sessions to reprocess negative emotions
      can amplify intimacy, increase connection, and subsequently lead to a change in
      problematic relationship patterns.

PMID- 11314550
TI  - A feminist analysis of self-help bestsellers for improving relationships: a
      decade review.
AB  - Self-help literature is pervasive and influential in the United States. A
      critical analysis of self-help books would help therapists to determine their
      utility for the therapeutic process and assist them in making reading
      recommendations to clients. In this study, a content analysis was conducted of
      the top 11 relationship self-help books on the New York Times Bestseller List
      over a period of 10 years (1988-1998) to determine the degree to which these
      books support a feminist approach to therapy. This study yielded three major
      findings. First, the number of feminist books, the number of nonfeminist books,
      and those falling in the middle across four components of feminist family therapy
      are about equal. However, the second major finding was that the top-selling books
      are more likely to be nonfeminist than feminist. The third finding is that most
      best-selling self-help books appear to have become less compatible with a
      feminist approach to relationships over time. This analysis encourages therapists
      to think critically about these best-selling books; it will also allow therapists
      to consider this methodology as a model for critically analyzing other books that
      they recommend to clients or use in their own professional development.

PMID- 11314551
TI  - Pulling on the heart strings: an emotionally focused approach to family life
      cycle transitions.
AB  - Transitions through the family life cycle can be stressful because they challenge
      attachment bonds between family members. Open communication and the processing of
      primary attachment emotions are crucial when family systems change. When family
      members are insecurely attached, such open communication is difficult, and people
      tend to get stuck in absorbing states of secondary defensive affect. Emotionally
      focused therapy (EFT) can be particularly helpful by encouraging family members
      to express primary emotions. This expression then fosters renegotiation of bonds
      and the clarification of attachment needs and concerns. Case examples illustrate
      how EFT can be applied to each family life cycle stage.

PMID- 11314552
TI  - Internal family systems therapy for children in family therapy.
AB  - This article presents a developmentally supported implementation of Internal
      Family Systems Therapy for school-age children and their families. Relevant
      developmental characteristics of children are described. Suggestions for working
      with parents, child-oriented interventions, and a case example are presented.

PMID- 11314553
TI  - Resource-based reflective consultation: accessing client resources through
      interviews and dialogue.
AB  - This article presents an interventive, consultative method that is designed to
      elicit and to promote resource-based language between client families and their
      therapists. The reflexive interview process that this method entailed is
      described through case examples. Initially, resource-based language was generated
      from client interviews and shared in reflective dialogue with their therapists in
      a way that encouraged participants to consider different views and beliefs about
      themselves, each other, and their process together. Use of this consultative
      process in therapy added heightened awareness and respect for competencies
      possessed not only by the client families but by the therapists as well.

PMID- 11314554
TI  - Patterns of change in family-based aggression prevention.
AB  - Patterns of change on three intervention targets were examined in 151 families
      that participated in a family intervention designed to reduce and prevent
      children's aggressive behavior. Measures of parents' alliance and parenting
      skills and children's aggressive behavior were obtained at five times during the
      intervention. Three cluster analyses were conducted to identify patterns of
      change on each target. Linear and nonlinear patterns of improvement as well as
      two distinct patterns of no change were obtained. The patterns were
      differentiated by net improvement, overall level of skill, and trajectory of
      change. Family characteristics also differentiated the patterns and relations
      were found among patterns across intervention targets. The clinical implications
      of these findings are discussed.

PMID- 11314555
TI  - GAPS between MFT supervision assumptions and common practice: suggested best
      practices.
AB  - This article summarizes gaps between assumptions that appear in the literature,
      research, and accepted standards for marital and family therapy (MFT)
      supervision, and the common practice of supervisors. Issues that stem from these
      gaps are highlighted and recommendations are made for closing them. In an effort
      to refine the standard of practice for MFT supervision, best practice
      recommendations are offered for MFT supervision.

PMID- 11314556
TI  - A study of live supervisory phone-ins in collaborative family therapy: correlates
      of client cooperation.
AB  - The behavior of five supervisors, 19 trainee family therapists, and 20 clients
      before, during, and after 88 live supervisory phone-in events was examined in
      this study to determine the correlates of client cooperation. Following
      supervisory phone-in conversations, client cooperation was associated exclusively
      with the presence and quality of the collaborative behavior shown by the
      therapist. Isomorphism between the behavior of the supervisor and therapist was
      not associated with subsequent client cooperation, nor was any particular
      category of supervisor behavior. Surprisingly, isomorphism between the quality of
      supervisor and therapist behavior preceded those events where client resistance
      occurred.

PMID- 11314557
TI  - A graduate course in marriage and family enrichment.
AB  - Legislation aimed at decreasing the divorce rate and the resurgence of interest
      in marriage and family enrichment have propelled educators to consider how well
      they are training new therapists in the preventive approaches to therapy. In this
      article, we present a graduate course to educate students about the enrichment
      movement and skill- and competency-based approaches to family intervention. We
      provide a general outline for teaching the course as well as specific resources
      and guidelines that can be of value to all marriage and family therapy
      practitioners.

PMID- 11314558
TI  - Qualitative research in family therapy: a substantive and methodological review.
AB  - Over the last decade, marriage and family therapy (MFT) researchers have
      developed a growing interest in qualitative research. In this article, we review
      substantive and methodological trends in the published qualitative studies within
      the MFT field. The research is compared and contrasted in the following areas:
      General topic, epistemological theory, methodological theory, sampling and
      sample, data collection, data analysis procedure, and approach to reliability and
      validity. We also provide recommendations for future research.

PMID- 11314559
TI  - Ethics of ECT for children.

PMID- 11314560
TI  - Eating disorder and superior mesenteric artery syndrome.

PMID- 11314561
TI  - An electronic communication device for selective mutism.

PMID- 11314562
TI  - Quetiapine for Tourette's syndrome.

PMID- 11314563
TI  - Gender identity disorder in DSM?

PMID- 11314564
TI  - Impact of media on children and adolescents: a 10-year review of the research.
AB  - OBJECTIVE: To review the research literature published within the past 10 years
      regarding the impact of media on children and adolescents. METHOD: Media
      categories researched with computer technology included television and movies,
      rock music and music videos, advertising, video games, and computers and the
      Internet. RESULTS: Research prior to 1990 documented that children learn
      behaviors and have their value systems shaped by media. Media research since has
      focused on content and viewing patterns. CONCLUSIONS: The primary effects of
      media exposure are increased violent and aggressive behavior, increased high-risk
      behaviors, including alcohol and tobacco use, and accelerated onset of sexual
      activity. The newer forms of media have not been adequately studied, but concern
      is warranted through the logical extension of earlier research on other media
      forms and the amount of time the average child spends with increasingly
      sophisticated media.

PMID- 11314565
TI  - Parent-based therapies for preschool attention-deficit/hyperactivity disorder: a
      randomized, controlled trial with a community sample.
AB  - OBJECTIVE: To evaluate two different parent-based therapies for preschool
      attention-deficit/hyperactivity disorder (ADHD) in a community sample. METHOD:
      Three-year-old children displaying a preschool equivalent of ADHD (n = 78) were
      randomly assigned to either a parent training (PT; n = 30), a parent counseling
      and support (PCO&S; n = 28), or a waiting-list control group (n = 20). The PT
      group received coaching in child management techniques. The PC&S group received
      nondirective support and counseling. Measures of child symptoms and mothers' well
      being were taken before and after intervention and at 15 weeks follow-up.
      RESULTS: ADHD symptoms were reduced (F2,74 = 11.64; p < .0001) and mothers' sense
      of well-being was increased by PT relative to both other groups (F2,74 = 10.32; p
      < .005). Fifty-three percent of children in the PT group displayed clinically
      significant improvement (chi 2 = 4.08; p = .048). CONCLUSIONS: PT is a valuable
      treatment for preschool ADHD. PC&S had little effect on children's behavior.
      Constructive training in parenting strategies is an important element in the
      success of parent-based interventions. Psychostimulants are not a necessary
      component of effective treatment for many children with preschool ADHD.

PMID- 11314566
TI  - Prevalence of psychiatric disorders in youths across five sectors of care.
AB  - OBJECTIVE: To examine the prevalence of psychiatric disorders among youths from
      the following five public sectors of care: alcohol and drug services (AD), child
      welfare (CW), juvenile justice (JJ), mental health (MH), and public school
      services for youths with serious emotional disturbance (SED) in San Diego,
      California. METHOD: The Diagnostic Interview Schedule for Children was
      administered between October 1997 and January 1999 for 1,618 randomly selected
      youths aged 6-18 years who were active in at least one of the five sectors.
      RESULTS: Fifty-four percent of the participants met criteria for at least one
      study disorder. Attention-deficit/hyperactivity disorder (ADHD) and disruptive
      behavior disorders (50%) were much more common than anxiety (10%) or mood (7%)
      disorders. Youths who were active in the MH and SED sectors were more likely than
      those not in these sectors to meet criteria for a disorder; youths in the CW
      sector were least likely. CONCLUSIONS: Rates of psychiatric disorders,
      specifically ADHD and disruptive behavior disorders, are extremely high for
      youths in public sectors of care. Rates are generally higher in sectors designed
      to serve youths with psychiatric needs, but the prevalence of disorders was also
      high in sectors not specifically designed for this need (e.g., CW and JJ).

PMID- 11314567
TI  - Prevalence of adolescent substance use disorders across five sectors of care.
AB  - OBJECTIVE: To examine the prevalence of substance use disorders (SUDs) among
      adolescents who received services in one or more of the following public sectors
      of care: alcohol and drug (AD), juvenile justice (JJ), mental health (MH), public
      school-based services for youths with serious emotional disturbance (SED), and
      child welfare (CW), in relation to age, gender, and service sector affiliation.
      METHODS: Participants included 1,036 adolescents aged 13 to 18 years, randomly
      sampled from all youths who were active in at least one of the above five sectors
      of care (N = 12,662) in San Diego County California. SUDs were assessed through
      structured diagnostic interviews conducted from October 1997 through January
      1999. RESULTS: SUDs were found for youths in all sectors of care, with lifetime
      rates of 82.6% in AD, 62.1% in JJ, 40.8% in MH, 23.6% in SED, and 19.2% in CW.
      Rates of SUDs were significantly higher among older youths and males. Sector
      differences held even when accounting for the effects of age and gender.
      CONCLUSIONS: SUDs are highly prevalent among youths receiving care in the AD
      service sector as well as other sectors, particularly JJ and MH. These findings
      have implications for assessment, treatment, and service coordination for youths
      with SUDs in diverse sectors of public care.

PMID- 11314568
TI  - Gender differences in suicide attempts from adolescence to young adulthood.
AB  - OBJECTIVE: To examine associations of age, gender, and psychosocial factors
      during adolescence with risk of suicide attempt between ages 19 and 23 years.
      METHOD: Initial assessments were conducted with 1,709 adolescents (aged 14-18) in
      western Oregon between 1987 and 1989. One year later, 1,507 participants returned
      for a second assessment. A subset of participants (n = 941; 57.2% women) had a
      third diagnostic assessment after turning 24 (between 1993 and 1999). Information
      on suicidal behavior, psychosocial risk factors, and lifetime DSM-III-R
      psychiatric diagnosis was collected at each assessment. RESULTS: The suicide
      attempt hazard rate for female adolescents was significantly higher than for male
      adolescents (Wilcoxon chi 2(1)[n = 941] = 12.69, p < .001). By age 19, the
      attempt hazard rate for female adolescents dropped to a level comparable with
      that of male adolescents. Disappearance of the gender difference for suicide
      attempts by young adulthood was not paralleled by a decrease in the gender
      difference for major depression. Adolescent suicidal behavior predicted suicide
      attempt during young adulthood for female, but not male, participants. Adolescent
      psychosocial risk factors for suicide attempt during young adulthood were
      identified separately for girls and boys. CONCLUSIONS: Unlike depression, the
      elevated incidence rate of suicide attempts by adolescent girls is not maintained
      into young adulthood. Screening and prevention implications are discussed.

PMID- 11314569
TI  - Violence exposure, psychological trauma, and suicide risk in a community sample
      of dangerously violent adolescents.
AB  - OBJECTIVE: To examine violence exposure, violent behaviors, psychological trauma,
      and suicide risk in a community sample of dangerously violent adolescents by
      comparison with a matched community sample of nonviolent adolescents. METHOD:
      Anonymous self-report questionnaires were administered in the 1992-1993 school
      year to students in grades 9 through 12, in six public high schools located in
      Ohio and Colorado (N = 3,735). From this sample, 484 adolescents (349 males, 135
      females) who reported attacking someone with a knife or shooting at someone
      within the past year (i.e., dangerously violent adolescents) were drawn. Four
      hundred eighty-four controls were also selected and matched on gender, age in
      years, ethnicity, area of residence, and family structure. RESULTS: Dangerously
      violent adolescents reported higher levels of exposure to violence and
      victimization than did matched controls. Dangerously violent females were more
      likely to score in the clinical range of depression, anxiety, posttraumatic
      stress, anger, and dissociation than were control females and violent males; they
      also had significantly higher levels of suicide potential. CONCLUSIONS: Students
      who have been known to commit violent acts should be adequately assessed for
      violence exposure and symptoms of psychological trauma, with special attention
      given to the suicide potential of violent females.

PMID- 11314570
TI  - The DISC Predictive Scales (DPS): efficiently screening for diagnoses.
AB  - OBJECTIVE: To derive and test a series of brief diagnosis-specific scales to
      identify subjects who are at high probability of meeting diagnostic criteria and
      those who may safely be spared more extensive diagnostic inquiry. METHOD:
      Secondary data analysis of a large epidemiological data set (n = 1,286) produced
      a series of gate and contingent items for each diagnosis. Findings were
      replicated in a second retrospective analysis from a residential care sample (n =
      884). The DISC Predictive Scales (DPS) were then used prospectively as a self
      report questionnaire in two studies, in which parents (n = 128) and/or
      adolescents (n = 208) had subsequent diagnostic interviewing with the Diagnostic
      Interview Schedule for Children or the Schedule for Affective Disorders and
      Schizophrenia for School-Age Children. RESULTS: All analyses showed that gate
      item selection was valid and that any missed cases were due solely to
      inconsistent reports on the same questions. Screening performance of the full
      scales was shown to be good, and substantial reductions in scale length were not
      associated with significant changes in discriminatory power. CONCLUSIONS: The DPS
      can accurately determine subjects who can safely be spared further diagnostic
      inquiry in any diagnostic area. This has the potential to speed up structured
      diagnostic interviewing considerably. The full DPS can be used to screen
      accurately for cases of specific DSM-III-R disorders.

PMID- 11314571
TI  - Reliability of the Washington University in St. Louis Kiddie Schedule for
      Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling
      sections.
AB  - OBJECTIVE: To investigate the reliability of the Washington University in St.
      Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS)
      mania and rapid cycling sections. METHOD: The 1986 version of the KSADS was
      modified and expanded to include onset and offset of each symptom for both
      current and lifetime episodes, expanded prepubertal mania and rapid cycling
      sections, and categories for attention-deficit/hyperactivity disorder and other
      DSM-IV diagnoses. To optimize diagnostic research, skip-outs were minimized.
      Subjects participated in the ongoing "Phenomenology and Course of Pediatric
      Bipolar Disorder" study. Mothers and children were interviewed separately by
      research nurses who were blind to diagnostic group status. In addition, ratings
      of off-site child psychiatrists, made from the narrative documentation given for
      each WASH-U-KSADS item, were compared with research nurse ratings. This work was
      performed between 1995 and 2000. RESULTS: There was 100% interrater reliability,
      five consecutive times, as both interviewer and observer after 10 to 15 trials.
      The kappa values of comparisons between research nurse and off-site blind best
      estimate ratings of mania and rapid cycling sections were excellent (0.74-1.00).
      High 6-month stability for mania diagnoses (85.7%) and for individual mania items
      and validity against parental and teacher reports were previously reported.
      CONCLUSIONS: The WASH-U-KSADS mania and rapid cycling sections have acceptable
      reliability.

PMID- 11314572
TI  - Cultural influences on diagnosis and perception of Tourette syndrome in Costa
      Rica.
AB  - BACKGROUND AND OBJECTIVES: Tourette syndrome (TS) is a neuropsychiatric disorder
      in which the pattern of symptom presentation can vary greatly between
      individuals. Although globally described, TS has not been well characterized in
      many parts of the world. Differences in individual and cultural perceptions of TS
      may impact its expression and recognition in some countries, confounding the
      identification of affected individuals. This study examines the phenomenology and
      presentation of TS in Costa Rica. METHOD: Clinical data on 85 Costa Rican
      subjects with TS (aged 5-29 years) initially recruited for a genetic study
      between 1996 and early 2000 were obtained by direct interview and review of
      medical records. RESULTS: The clinical characteristics of TS were similar to that
      found elsewhere. The gender ratio was 4.6:1, the mean age of onset was 6.1 years,
      and 20% of subjects had coprolalia. However, the perceived impact of TS was
      different. Many subjects denied that their TS caused impairment or distress, even
      when objective evidence of impairment was available. CONCLUSIONS: TS in Costa
      Rica is phenomenologically similar to TS seen in other parts of the world, but
      differs in perceived impairment. In other countries where cultural forces affect
      disease definition, close scrutiny of symptom expression and possible adjustment
      of phenotype definition may be important.

PMID- 11314573
TI  - Internalizing and externalizing behavior of children with enlisted Navy mothers
      experiencing military-induced separation.
AB  - OBJECTIVES: To examine whether children with Navy mothers exhibit higher levels
      of internalizing and externalizing behavior than children in civilian families
      and whether deployment affects children's internalizing and externalizing
      behavior. METHOD: Navy mothers who experienced deployment completed a measure
      assessing children's internalizing and externalizing behavior before and after a
      deployment (and at similar intervals for the Navy and civilian comparison
      groups). Data collection took place between 1996 and 1998. RESULTS: Navy children
      with deployed mothers exhibited higher levels of internalizing behavior than
      children with nondeployed Navy mothers. Navy children whose mothers experienced
      deployment were more likely to exhibit clinical levels of internalizing behavior
      than Navy children with nondeployed mothers or civilian children. Group
      differences, however, were modest and overall mean scores were in the normal
      range. CONCLUSIONS: Findings do not suggest greater pathology in children of Navy
      mothers; however, findings do indicate we should be particularly attentive of
      deployed mothers and their children.

PMID- 11314574
TI  - Adolescents with gender identity disorder who were accepted or rejected for sex
      reassignment surgery: a prospective follow-up study.
AB  - OBJECTIVE: To conduct a prospective follow-up study with 20 treated adolescent
      transsexuals to evaluate early sex reassignment, and with 21 nontreated and 6
      delayed-treatment adolescents to evaluate the decisions not to allow them to
      start sex reassignment at all or at an early age. METHOD: Subjects were tested on
      their psychological, social, and sexual functioning. Follow-up interviews were
      conducted from March 1995 until July 1999. Treated patients had undergone surgery
      1 to 4 years before follow-up; nontreated patients were tested 1 to 7 years after
      application. Within the treated and the nontreated group, pre- and posttreatment
      data were compared. Results between the groups were also compared. RESULTS:
      Postoperatively the treated group was no longer gender-dysphoric and was
      psychologically and socially functioning quite well. Nobody expressed regrets
      concerning the decision to undergo sex reassignment. Without sex reassignment,
      the nontreated group showed some improvement, but they also showed a more
      dysfunctional psychological profile. CONCLUSIONS: Careful diagnosis and strict
      criteria are necessary and sufficient to justify hormone treatment in adolescent
      transsexuals. Even though some of the nontreated patients may actually have
      gender identity disorder, the high levels of psychopathology found in this group
      justify the decision to not start hormone treatment too soon or too easily.

PMID- 11314576
TI  - Measurement reliability.

PMID- 11314575
TI  - Case series: neuropsychiatric symptoms with pediatric systemic lupus
      erythematosus.
AB  - OBJECTIVE: To describe the psychiatric presentation, serologic findings, and
      neuroimaging patterns in children and adolescents with central nervous system
      involvement with systemic lupus erythematosus (CNS-SLE). METHOD: Pediatric
      patients with psychiatric symptoms who fulfilled the 1997 revised diagnostic
      American College of Rheumatology criteria for SLE were studied. Complement
      levels, and anti-double-stranded DNA, anti-Smith, anti-phospholipid, and anti
      neuronal antibodies were evaluated. Computed tomography, magnetic resonance
      imaging, and single photon emission computed tomography (SPECT) neuroimaging
      studies were reviewed. RESULTS: The 10 patients with CNS-SLE presented with
      psychosis, mood disturbance, or confusion, and 8 patients had concomitant
      neurologic symptoms. The 8 girls and 2 boys ranged in age from 7.5 to 17 years.
      Serum anti-neuronal antibodies were positive with onset of symptoms and declined
      with improvement. Initial SPECT was abnormal in all 10 patients and remained
      abnormal. CONCLUSION: SPECT and anti-neuronal antibodies help confirm CNS
      involvement in patients with SLE and neuropsychiatric symptoms.

PMID- 11314577
TI  - Genetics of childhood disorders: XXV. Velocardiofacial syndrome.

PMID- 11314578
TI  - Summary of the practice parameters for the assessment and treatment of children
      and adolescents with suicidal behavior.
AB  - These guidelines review what is known about the epidemiology, causes, management,
      and prevention of suicide and attempted suicide in young people. Detailed
      guidelines are provided concerning the assessment and emergency management of the
      children and adolescents who present with suicidal behavior. The guidelines also
      present suggestions on how the clinician may interface with the community. Crisis
      hotlines, method restriction, educational programs, and screening/case-finding
      suicide prevention strategies are examined, and the clinician is advised on media
      counseling. Intervention in the community after a suicide, minimization of
      suicide contagion or imitation, and the training of primary care physicians and
      other gatekeepers to recognize and refer the potentially suicidal child and
      adolescent are discussed.

PMID- 11314579
TI  - Use of etanercept in children.

PMID- 11314580
TI  - [The structure of the skin of the ear in domesticated pigs, with special
      reference to their use for human dermatological research. 2. Specific histology
      of the integument].
AB  - Based on light microscopy, the study describes the specific histology of the ear
      integument of the white domesticated pig. After careful tissue fixation and
      embedding, routine histological staining, collagen fibre staining, fat
      demonstration based on frozen sections, and ink injection of the integumental
      blood vessel system were applied. A detailed description is presented of the
      structure of the skin layers (epidermis, dermis, hypodermis), the ear cartilage
      envelopes (fascia, perichondrium), the plica scaphae, the blood vessel
      distribution, the architecture of the collagen fibre bundles, as well as the hair
      follicles and the skin glands (sebaceous glands, apocrine tubular glands). The
      results are discussed with regard to a direct comparison with the histological
      structure of the human integument, and the advantages and disadvantages of the
      use of the porcine ear skin as model system in human dermatological research are
      emphasized.

PMID- 11314581
TI  - [Laboratory investigation of the chemical disinfection against different
      developmental stages of the housefly (Musca domestica Linnaeus, 1758)].
AB  - Possibilities for disinfection of the developmental stages from the housefly
      (Musca domestica) were investigated under laboratory conditions. The
      developmental stages (eggs, larvae I, II, III, pupae and adults) were sprayed
      with solutions of disinfectants on the basis of p-chlorine-m-cresol and o
      phenylphenol at different concentrations (0.025%-3%). The effectiveness of both
      disinfectants was established by determining the emergence rate of eggs and pupae
      and of the live evidence of larvae and adults. Transmission electron microscopic
      investigations of the cover of the eggs revealed the bactericidal effect of both
      disinfectants. These results show the necessity of extending its use also to
      noxious arthropods.

PMID- 11314582
TI  - [Capillaries of the myocardium of Lama (Lama glama)].
AB  - The heart of 12 adult llamas, one female and 11 males, 2-7 years of age, was
      studied gross-anatomically (absolute and relative heart weight) and microscopic
      anatomically (left and right ventricular wall, left auricle). Comparing the 9
      younger animals (2-3 years old) with the 3 older llamas (5-7 years old) a
      significant increase of the absolute heart weight and of the number of
      capillaries per mm2 and a significant decrease of the intercapillary distance in
      the left ventricular wall was found. This results in an increase of capillarity
      in the studied heart regions (5.5% compared to 6.9%). The simultaneous increase
      of the capillary-to-myocyte-ratios from 0.9 to 1.1 shows a significant
      correlation to the cross-sectional area of the myocytes (r = 0.79) and an also
      significant but negative correlation to the number of myocytes per mm2 (r = 
      0.82). In both groups the cross-sectional area of the myocytes and their diameter
      differs significantly in the three regions of the heart (left ventricular wall-
      214 micron 2 resp. 17.5 microns; right ventricular wall--156 micron 2 resp. 15.5
      microns; left auricle--96 micron 2 resp. 11.5 microns). It is to be supposed,
      that the morphological conditions of the cardiac vascular supply of llamas living
      in an altitude of 4000 m are improving with age.

PMID- 11314583
TI  - [Efficacy evaluation of epsiprantel (Cestex) against Echinococcus mutilocularis
      in dogs and cats].
AB  - Helminth-free dogs and cats were experimentally infected with protoscoleces of
      Echinococcus multilocularis and used in controlled trials for efficacy evaluation
      of the cestodicide epsiprantel. In two separate trials each 4 dogs were treated
      at day 20 post infection (p.i.) with average oral dosages of 5.1 (4.9-5.3) and
      5.4 (5.2-5.8) mg/kg body weight (b.w.) epsiprantel, respectively, and necropsied
      at day 24 p.i. Among each 4 dogs of the two untreated control groups all animals
      were infected and had high intestinal worm burdens with averages of 33.575 and
      100.725 E. multilocularis specimens per animal (individual worm burdens in group
      Ib 59,500-149,800, group IIb 20,500-43,200); in the two groups of treated dogs
      the average worm burdens were reduced by 99.6 and 99.9%. Among 8 treated dogs 4
      were helminth-free, the other 4 had residual worm burdens (10-70 in 3 dogs, 1480
      in 1 dog). In each 5 cats single oral treatments with average doses of 2.7 (2.7
      2.8) and 5.5 (5.5-5.5) mg/kg b.w. epsiprantel were 100% effective against E.
      multilocularis 20 days p.i. and eliminated the worm burdens from all 10 animals.
      In the untreated group of 5 cats the average worm burden was 2864 per animal
      (individual worm burdens 20-6830). Side effects of the drug treatment were not
      observed. The results of the study show that in single therapeutic dosages
      recommended by the producer (dogs 5.5 mg, cats 2.75 mg/kg b.w.) epsiprantel
      eliminates E. multilocularis to over 99% or completely, but residual worm burdens
      may persist in some animals.

PMID- 11314584
TI  - [Content of minerals (Na,K,Ca,Mg) and of trace elements (Fe,Cu and Zn) in 13
      different tissues of fallow deer (Dama dama L.) of various ages].
AB  - At male deer in the age of 15 and 27 months, at experimentally induced
      cryptorchids and at castrated animals analyses of the content of Na, K, Ca, Mg,
      Fe, Cu and Zn in 13 different tissues were performed. In the liver of newborn
      animals solely the content of Fe, Cu and Zn was determined. The significance of
      the content of the mentioned elements in the various tissues is described. In the
      liver of the newborn animals stores of Fe, Cu an Zn were identified. The values
      can be used as a basis for analyses at deer with a growth inhibition caused by a
      lack of sodium chloride Fe, Cu and Zn.

PMID- 11314585
TI  - Starvation-induced pathobiology in the gut of carp (Cyprinus carpio L.).
AB  - In order to assess the effects of starvation on intestinal intraepithelial
      lymphocytes (i-IEL) count and histological changes of the carp gut mucosa, one
      group of fish (n = 10) were fed commercially prepared standard diets and another
      group of fish (n = 10) were starved for 4 weeks. Carp starved for 4 weeks
      developed enteropathy, comprising folds atrophy, stratum compactum hyperplasia,
      significant periodic-acid-Schiff (PAS)-positive (P < 0.00001), but not Alcian
      blue (ALB)-positive, goblet cell (GC) hyperplasia and a significant decrease (P <
      0.00001) in i-IEL numbers. These changes were associated with a dense cellular
      infiltrate into the lamina propria. Taken together, these data suggest that the
      pathobiology of starvation-induced i-IELs decrease, matching PAS-positive goblet
      cell proliferation and inflammatory cells homing to the gut, could be classified
      as a non-infectious enteropathy induced by starvation.

PMID- 11314586
TI  - [Rectum diverticulum/perineal hernia surgery through longitudinal contracting of
      the wall of the rectum].
AB  - Older male dogs often exhibit the symptoms of rectum diverticulum and perineal
      hernia. In order to point out the often common reason of these disorders, the
      term "rectum diverticulum/perineal hernia complex" has been introduced. In a
      large group of such patients two methods of surgical correction of this problem
      were retrospectively evaluated. Only patients were included in this evaluation
      that were euthanized if recurrence occurred. In 21 patients (group 1) the often
      performed method of Bojrab was used, both in rectum diverticulum and in perineal
      hernia operations. In group 2 15 dogs were subjected to the same operation
      technique, but we performed an additional pleating contraction of the herniated
      gut wall layers. In case of visible recurrence at an age of at least 11 years the
      dogs were euthanized. Group 1 showed a postoperative survival time of 3.61 +/-
      0.96 years until recurrence, group 2 revealed recurrence not before 4.93 +/- 0.93
      years post operationem. The difference is significant (p < 0.05). It is the
      opinion of the authors that additional longitudinal contracting by pleating of
      the gut markedly prolonges the point of time when recurrence appears.

PMID- 11314587
TI  - Case report: fibroma on the end of the tail of a cow.
AB  - An unusual case of fibroma on the end of the tail of a 7-year-old cross-breed
      cow. The most prominent clinical findings were the size and weight of the tumour,
      and the tail length. The extension of the tail was apparently caused by the
      weight of the tumour.

PMID- 11314588
TI  - [Yersinia enterolitica infections: 2. Impact on human health].
AB  - The clinical picture of yersiniosis in humans and its prevalence in the human
      population is described in detail. Mass production of animals, development of
      meat factories based on sophisticated chains of cold storage units and
      international trade of meat products and animals are believed to be the reasons
      for the increasing prevalence of yersiniosis in humans. In Germany, anti-Yersinia
      antibodies are found in up to 40% of the average population. The financial losses
      for the national economy cannot be judged. Of special interest for industrial
      medicine are sequelae-like reactive arthritis in exposed occupational groups such
      as veterinarians or butchers. However, the lack of national and international
      data makes the assessment of the potential of yersiniosis as a zoonosis
      difficult. Therefore, intensive and interdisciplinary research is needed to close
      the gaps described. Already proven and proposed countermeasures at the different
      stages of mass production of animals and reglementations for international trade
      of meat products and animals are introduced. The need for development not only of
      cheap and rapid diagnostic tools but also for countermeasures and treatment
      strategies is discussed.

PMID- 11314589
TI  - [Electrolyte levels in feces and urine in healthy breeding calves between the
      ages of 5 days to 6 months].
AB  - In contrast to the situation in adult cattle there are high concentrations of
      sodium and low concentrations of potassium in the faeces of suckling calves. It
      was investigated in this study in which stage of the development of the ruminant
      these changes in electrolyte levels occur, and whether there are changes in
      electrolyte levels in urine as well. Samples of faeces and urine from healthy
      calves were examined fortnightly starting with the 5th day after birth. There was
      a distinct decrease in sodium concentration in faecal water within the first
      three weeks of life, i.e. without any relation to the intake of solid feed.
      However, the levels of sodium, potassium and chloride in urine samples and of
      potassium in faecal water increased with the development of rumination. The
      concentration of chloride in faeces was on a low level during the whole period of
      investigation.

PMID- 11314590
TI  - [The structure of the skin of the ear in domesticated pigs, with special
      reference to their use for human dermatological research. 1. Macroscopic aspects
      and hair coat].
AB  - To begin with, the study describes macroscopically the typical pigmentation, form
      and surface sculpture of the external ear of the white domesticated pig. Then the
      palpable stability and elasticity of the ear integument is analyzed, followed by
      a detailed and microscopically assisted description of the fine relief of the
      skin surface, the hair line, the hair density, the angle of hair follicle
      insertion, and the arrangement of hair follicles on both sides of the auricle.
      The results obtained are discussed with special regard to the use of the porcine
      ear integument as a model for human skin.

PMID- 11314591
TI  - Plenty of room at the bottom.

PMID- 11314592
TI  - A new occlusal splint for treating bruxism and TMD during orthodontic therapy.

PMID- 11314593
TI  - A comparison of standard edgewise, preadjusted edgewise, and tip-edge in Class II
      extraction treatment.

PMID- 11314594
TI  - A new bracket-positioning gauge.

PMID- 11314595
TI  - The art of the initial phone call.

PMID- 11314596
TI  - Mandibular widening by distraction osteogenesis.

PMID- 11314597
TI  - Asymmetric distalization with a TMA transpalatal arch.

PMID- 11314598
TI  - Pranidipine, a 1,4-dihydropyridine calcium channel blocker that enhances nitric
      oxide-induced vascular relaxation.
AB  - Pranidipine, a long acting 1,4-dihydropyridine calcium channel blocker, prolongs
      nitric oxide (NO)-mediated relaxation of rat aorta; it prolongs acetylcholine
      induced relaxation in presence of endothelium as well as nitroglycerin-induced
      relaxation in absence of endothelium. In rat aorta the effect of pranidipine on
      NO-mediated relaxation is cyclic guanosine monophosphate (cGMP)-independent, but
      in guinea pig carotid artery the same effect of pranidipine is cGMP-dependent. It
      has been reported that in co-cultured human endothelial and smooth muscle cells
      pranidipine, at a higher concentration (10(-6) M), enhances vasorelaxant effect
      of NO by blocking NO decomposition. The enhancement of NO action by pranidipine
      differs from the direct NO-releasing action of other 1,4-dihydropyridines. It is
      expected that enhancement of NO-induced vasodilatation will lead to a venodilator
      action in vivo and less peripheral edema. The target organ protective effects of
      pranidipine are also reviewed in this article.

PMID- 11314599
TI  - UR-3216: a manageable oral GPIIb/IIIa antagonist.
AB  - UR-3216, a prodrug, is a novel, selective, and orally active platelet surface
      glycoprotein (GPIIb/IIIa) receptor antagonist. The most important property of UR
      3216 is the very tight binding of its active metabolite to platelets (Ki for
      resting platelets is < 1 nM). UR-2992, the active form of UR-3216, binds to
      platelets for a long period of time, while the unbound drug is rapidly cleared.
      Therefore, after an initial loading dose of 0.1 mg/kg, only once daily repeated
      low maintenance doses of UR-3216 (< 0.05 mg/kg p.o.) are required. This regimen
      maintains a high level of inhibition of platelet aggregation and, due to a small
      peak-to-trough ratio, severe bleeding is avoided. The therapy with UR-3216 is
      easy to manage, because it has low peak-to-trough ratio and high efficacy (> 80%
      inhibition of platelet aggregation). In addition, UR-3216 does not produce
      excessive bleeding or thrombocytopenia and does not interact with abciximab. UR
      3216 is excreted mostly in bile, so that it will not accumulate in patients with
      chronic renal dysfunction. UR-2316 has the following abciximab-like features: (a)
      its half-lives for residence on platelets, inhibition of platelets aggregation
      and bleeding time prolongation are 60 to 80 h, 24, and 2 h, respectively; (b) its
      receptor binding occupancy is similar to that of abciximab (Mab1 is inhibited and
      Mab2 is unaltered). In conclusion, UR-3216 is a promising, orally active
      GPIIb/IIIa antagonist for the treatment of cardiovascular diseases.

PMID- 11314600
TI  - Basic experimental studies and clinical aspects of gadolinium salts and chelates.
AB  - Gadolinium is a lanthanide that has in recent years become more commonly present
      in our society. Organic chelates of gadolinium are increasingly used as contrast
      agents for the imaging of body fluids. Although adverse reactions to these agents
      are uncommon, it is known that gadolinium salts can bring about a wide variety of
      changes in physiology. Gadolinium chloride is widely used experimentally as an
      inhibitor of stretch-activated ion channels and physiological responses of
      tissues to mechanical stimulation. It is also employed as a selective inhibitor
      of macrophages in vivo. In this review, the known biochemical actions of
      gadolinium are brought together with its in vivo pharmacology and toxicology.

PMID- 11314601
TI  - Cardiovascular effects of raloxifene hydrochloride.
AB  - Raloxifene hydrochloride binds to the estrogen receptor and shows tissue
      selective effects; thus, it belongs to a class of drugs recently described as
      selective estrogen receptor modulators (SERMs). Tissue selectivity of raloxifene
      may be achieved through several mechanisms: the ligand structure, interaction of
      the ligand with different receptor subtypes in various tissues, and intracellular
      events after ligand binding. Raloxifene has estrogen-agonist effects on bone and
      lipids and estrogen antagonist effects on the breast and uterus. In addition to
      its well established effects on osteoporosis, recent preclinical and clinical
      findings suggest that raloxifene also possesses beneficial effects on the
      cardiovascular system. These findings indicated that raloxifene may have
      cardioprotective properties without an increased risk of cancer or other side
      effects. Raloxifene has been shown to reduce total and low-density lipoprotein
      cholesterol concentrations in plasma, an effect similar to that produced by
      estrogens. Unlike estrogens, however, raloxifene does not increase high-density
      lipoprotein cholesterol and triglyceride levels in plasma. Endothelium is thought
      to play an important role in the genesis of atherosclerosis. Several lines of
      evidence suggest that an intervention with endothelial function might influence
      the progression of coronary disease and the incidence of cardiovascular events.
      Raloxifene increases the nitric oxide/endothelin-1 ratio, and improves
      endothelium-dependent vasomotion in post-menopausal women to the same extent as
      estrogens. Furthermore, in two randomized trials on post-menopausal women
      raloxifene reduced homocysteine levels, another independent risk factor for the
      development of cardiovascular disease. Although estrogens remain the drugs of
      choice in the hormonal therapy of most postmenopausal women, raloxifene may
      represent and alternative in women who are at risk of coronary artery disease.

PMID- 11314602
TI  - Angiotensin receptor blockers and the kidney: possible advantages over ACE
      inhibition?
AB  - This review deals with similarities and differences between the effects of ACE
      inhibitors and AT1-receptor blockers in the kidney. Specific receptor blockade
      has demonstrated that the beneficial effects of AT1 blockers arise from two
      mechanisms: the reduction of the AT1 receptor mediated response and the increase
      in plasma levels of Ang II through the AT1-receptor blockade, which leads to
      increased stimulation of the AT2 receptor (the so-called yin-yang effect). Both
      ACE inhibition and AT1-receptor blockade provide significant renal protection in
      the majority of experimental animal models of kidney diseases. AT1 receptor
      blockade may offer additional clinical benefits over ACE inhibitor treatment,
      particularly in the kidney, where AT1-receptor blockade does not cause the fall
      in glomerular filtration rate seen with ACE inhibitor treatment. A number of long
      term clinical studies currently running should show the real value of this new
      class of compounds in the management of hypertension and associated cardiorenal
      diseases.

PMID- 11314603
TI  - Bopindolol: pharmacological basis and clinical implications.
AB  - Bopindolol, a non-selective antagonist of beta 1- and beta 2-adrenoceptors (ARs),
      has been found by pharmacological, molecular biological techniques and molecular
      modeling to have several unique properties. Bopindolol produces sustained
      blockade of beta 1- and beta 2-ARs, has intrinsic sympathomimetic as well as
      membrane stabilizing actions, inhibits renin secretion, and interacts with 5-HT
      receptors. Also, our recent molecular modeling studies identified possible
      interaction sites between bopindolol and beta-AR subtypes. The reviewed studies
      support our findings that bopindolol is non-selective for beta 1- and beta 2-ARs,
      has low affinity for beta 3-AR subtype and has pharmacological properties that
      are likely to be beneficial in the treatment of cardiovascular diseases.

PMID- 11314604
TI  - Clinical ethics committees: a worldwide development.

PMID- 11314605
TI  - Support for ethical dilemmas in individual cases: experiences from the Neu
      Mariahilf Hospital in Goettingen.
AB  - Prompted by a recommendation of the two Christian hospital associations in
      Germany, the Neu-Mariahilf Hospital in Gottingen set up a health ethics committee
      in autumn 1998. It is the committee's task to give support to staff members,
      patients and their relatives in individual cases where ethical dilemmas arise.
      The following article describes the committee's work by means of three cases.

PMID- 11314606
TI  - Clinical ethics support services in the UK: an investigation of the current
      provision of ethics support to health professionals in the UK.
AB  - OBJECTIVE: To identify and describe the current state of clinical ethics support
      services in the UK. DESIGN: A series of questionnaire surveys of key individuals
      in National Health Service (NHS) trusts, health authorities, health boards, local
      research ethics committees and health professional organisations. Interviews with
      chairmen/women of clinical ethics committees identified in the surveys. SETTING:
      The UK National Health Service. RESULTS: Responses to the questionnaires were
      received from all but one NHS trust and all but one health authority/board. A
      variety of models of clinical ethics support were identified including twenty
      formal clinical ethics committees (CECs). A further twenty NHS trusts expressed
      an intention to establish a CEC within the next twelve months. Most CECs in the
      UK have been in existence less than five years and are still defining their role.
      The chairmen identified education of committee members and contact with other
      ethics committees as important requirements for committee development. Problems
      were identified around lack of support for the committee and with raising the
      profile of the committee within the institution. There has been little evaluation
      of clinical ethics support services either in the UK or in other countries with
      longer established services. What evaluation has occurred has focused on process
      rather than outcome measures. CONCLUSIONS: Clinical ethics support services are
      developing in the UK. A number of issues have been identified that need to be
      addressed if such support services are to develop effectively.

PMID- 11314607
TI  - The Freiburg approach to ethics consultation: process, outcome and competencies.
AB  - The paper describes how ethics consultation can be valuable to health
      professionals, patients and their families in understanding and evaluating
      ethical values and their consequences in a particular situation. Ethics
      consultation as it is practised at the university hospital of Freiburg is a
      special professional service offered by members of an academic institution. The
      practical approach and the goals are illustrated by a case study showing the
      difficulties of deciding about the limitation of intensive care medicine after
      heart surgery in the setting of maximum treatment. Here, the ethics consultation
      was initiated by the relatives of the patient who wanted a decision to withhold
      further life-sustaining treatment. Following the experiences in Freiburg, it is
      concluded that clinical ethicists have to cover a variety of relevant fields of
      knowledge, need special analytical skills, and should have professional
      competence in counselling, including conflict mediation or crisis intervention.

PMID- 11314608
TI  - What triggers requests for ethics consultations?
AB  - OBJECTIVES: While clinical practice is complicated by many ethical dilemmas,
      clinicians do not often request ethics consultations. We therefore investigated
      what triggers clinicians' requests for ethics consultation. DESIGN: Cross
      sectional telephone survey. SETTING: Internal medicine practices throughout the
      United States. PARTICIPANTS: Randomly selected physicians practising in internal
      medicine, oncology and critical care. MAIN MEASUREMENTS: Socio-demographic
      characteristics, training in medicine and ethics, and practice characteristics;
      types of ethical problems that prompt requests for consultation, and factors
      triggering consultation requests. RESULTS: One hundred and ninety of 344
      responding physicians (55%) reported requesting ethics consultations. Physicians
      most commonly reported requesting ethics consultations for ethical dilemmas
      related to end-of-life decision making, patient autonomy issues, and conflict.
      The most common triggers that led to consultation requests were: 1) wanting help
      resolving a conflict; 2) wanting assistance interacting with a difficult family,
      patient, or surrogate; 3) wanting help making a decision or planning care, and 4)
      emotional triggers. Physicians who were ethnically in the minority, practised in
      communities under 500,000 population, or who were trained in the US were more
      likely to request consultations prompted by conflict. CONCLUSIONS: Conflicts and
      other emotionally charged concerns triggers consultation requests more commonly
      than other cognitively based concerns. Ethicists need to be prepared to mediate
      conflicts and handle sometimes difficult emotional situations when consulting.
      The data suggest that ethics consultants might serve clinicians well by
      consulting on a more proactive basis to avoid conflicts and by educating
      clinicians to develop mediation skills.

PMID- 11314609
TI  - Electronic communication in ethics committees: experience and challenges.
AB  - Experience with electronic communication in ethics committees at two hospitals is
      reviewed and discussed. A listserver of ethics committee members transmitted a
      synopsis of the ethics consultation shortly after the consultation was initiated.
      Committee comments were sometimes incorporated into the recommendations. This
      input proved to be most useful in unusual cases where additional, diverse inputs
      were informative. Efforts to ensure confidentiality are vital to this approach.
      They include not naming the patient in the e-mail, requiring a password for
      access to the listserver, and possibly encryption. How this electronic
      communication process alters group interactions in ethics committees is a
      fruitful area for future investigation.

PMID- 11314610
TI  - What is the role of clinical ethics support in the era of e-medicine?
AB  - The internet is becoming increasingly important in health care practice. The
      number of health-related web sites is rising exponentially as people seek health
      related information and services to supplement traditional sources, such as their
      local doctor, friends, or family. The development of e-medicine poses important
      ethical challenges, both for health professionals and for those who provide
      clinical ethics support for them. This paper describes some of these challenges
      and explores some of the ways in which those who provide clinical ethics support
      might respond creatively to them. By offering ways of responding to such
      challenges, both electronically and face-to-face, the providers of clinical
      ethics support can show themselves to be an indispensable part of good quality
      health care provision.

PMID- 11314611
TI  - Developing standards for institutional ethics committees: lessons from The
      Netherlands.
AB  - This article presents standards for setting up and educating institutional ethics
      committees (IECs). These standards are based on experiences in the Netherlands,
      where IECs have been established in a large number of health care institutions.
      Though the IEC has become a generally accepted institution within Dutch health
      care, there are concerns over its effectiveness regarding the improving of the
      moral quality of clinical decision making. Health care practitioners and members
      of IECs too, experience a gap between the IEC and the reality of the clinical
      environment. At this moment, there is interest in developing programmes which
      educate practitioners in moral issues and how to deal with them, using the method
      of a structured debate on the ward. The IEC will not be made obsolete by this
      development, but can play a guiding role in the implementation of such
      programmes. Current concerns are the lack of patient representation in the Dutch
      IEC, and the loss of contact with the local community of health care
      practitioners because of the merger of hospitals into bodies similar to UK
      National Health Service (NHS) trusts.

PMID- 11314612
TI  - Teaching old dogs new tricks--a personal perspective on a decade of efforts by a
      clinical ethics committee to promote awareness of medical ethics.
AB  - To incorporate medical ethics into clinical practice, it must first be understood
      and valued by health care professionals. The recognition of this principle led to
      an expanding and continuing educational effort by the ethics committee of the
      Vancouver General Hospital. This paper reviews this venture, including some
      pitfalls and failures, as well as successes. Although we began with consultants,
      it quickly became apparent that education in medical ethics must reach all health
      care professionals--and medical students as well. Our greatest successes came in
      the formative years of a medical career (i.e., in medical school and residency
      training programmes), but other efforts were not wasted, particularly among
      nurses and other health care professionals. Although this is a personal review of
      the experience in one institution, the lessons learnt in Vancouver are applicable
      to the further development of medical ethics in the UK.

PMID- 11314613
TI  - Clinical ethics committees and the formulation of health care policy.
AB  - For some time, clinical ethics committees (CECs) have been a prominent feature of
      hospitals in North America. Such committees are less common in the United Kingdom
      and Europe. Focusing on the UK, this paper evaluates why CECs have taken so long
      to evolve and assesses the roles that they should play in health care policy and
      clinical decision making. Substantive and procedural moral issues in medicine are
      differentiated, the former concerning ethicolegal principles and their
      paradigmatic application to clinical practice and the latter dealing with how
      such application should be negotiated in the face of disagreement and/or
      uncertainty. It will be argued that the role of CECs is both substantive and
      procedural. Provided that they do not overstep their appropriate moral and
      professional boundaries, CECs will be shown to have an important and positive
      function in improving hospital care within the UK and elsewhere.

PMID- 11314614
TI  - Legal aspects of clinical ethics committees.
AB  - In an increasingly litigious society where ritual demands for accountability and
      "taking responsibility" are now commonplace, it is not surprising that members of
      clinical ethics committees (CECs) are becoming more aware of their potential
      legal liability. Yet the vulnerability of committee members to legal action is
      difficult to assess with any certainty. This is because the CECs which have been
      set up in the UK are--if the American experience is followed--likely to vary
      significantly in terms of their functions, procedures, composition, structures
      and authority. As a consequence it is difficult to generalize about the legal
      implications. Nevertheless, despite these difficulties this article will outline
      the broad legal principles governing the potential liability of committee
      members. It will also consider the relationship between CECs and the courts. It
      begins, however, with a brief analysis of the relationship between ethics and law
      in committee deliberations, and in particular of the role of law and legal
      expertise on CECs.

PMID- 11314615
TI  - Clinical governance--watchword or buzzword?
AB  - In the latest reform of the National Health Service great emphasis has been
      placed on the achievement and maintenance of quality. Mechanisms for ensuring
      this are being set up under the general title of "clinical governance". What is
      the meaning of this term? The metaphor behind the phrase is of navigation through
      stormy seas, but who guides the helmsman? Clinical ethics committees could have a
      part to play in these changes, provided their role is properly understood.
      Clinical governance is concerned with management according to an agreed set of
      aims. The task of ethics committees is Socratic rather than managerial. They
      should ask fundamental questions about the ethical norms of the services provided
      and give critical appraisal of the moral character of institutional policies. If
      these tasks are carried out then governance may become a watchword rather than
      just another buzzword.

PMID- 11314616
TI  - Snapshots of five clinical ethics committees in the UK.
AB  - Each of the following papers gives an account of a different UK clinical ethics
      committee. The committees vary in the length of time they have been established,
      and also in the main focus of their work. The accounts discuss the development of
      the committees and some of the ethical problems that have been brought to them.
      The issues raised will be relevant for other National Health Service (NHS) trusts
      in the UK that wish to set up such a committee.

PMID- 11314617
TI  - Regulation of the new perfusion of the communication pollution; cyber pollution.

PMID- 11314618
TI  - Genetic origins of disease.

PMID- 11314619
TI  - Radiographic evaluation of bone formation in the pterygoid region after maxillary
      distraction with a rigid external distraction (RED) device.
AB  - In recent years, distraction osteogenesis has been used to correct skeletal
      disharmonies in the craniofacial region including the mandible and maxilla. Rigid
      external distraction has been used successfully to correct severe maxillary
      skeletal discrepancies. However, the characteristics of the newly formed bone
      have not been studied. A modified tomogram technique was used to analyze the
      radiological characteristics of the bone generated after maxillary advancement
      with rigid external distraction. The newly developed protocol may assist the
      clinician to evaluate the distracted area and to determine the length of
      stabilization required after active treatment with rigid external distraction.

PMID- 11314620
TI  - Successful mandibular reconstruction using a BMP bioimplant.
AB  - A bone morphogenetic protein bioimplant was used for primary reconstruction of a
      6-cm mandibular discontinuity defect, after a segmental resection of an
      ameloblastoma. Radiographic evidence of new bone induction was seen at 3 and 9
      months, postoperatively. A biopsy was taken at 9 months demonstrated viable new
      bone formation at the bioimplant site. This is the first reported case using a
      bone morphogenetic protein bioimplant in a human, followed by histological
      confirmation of new bone.

PMID- 11314621
TI  - Postoperative pain management using intravenous patient-controlled analgesia for
      pediatric patients.
AB  - Pain control is an important consideration after any surgical procedures.
      Especially in children, more attention and care are needed during the period of
      postoperative pain control, which must be both sufficiently safe and effective.
      In this respect, intravenous patient-controlled analgesia provides improved
      titration of analgesic drugs, thereby maintaining optimal analgesic status with
      few side effects. Thirty pediatric patients were randomly divided into two
      groups: the intravenous patient-controlled analgesia group (with nalbuphine HCl
      and ketorolac tromethamine) and the conventional pethidine HCl intramuscular
      group. The degree of analgesia was assessed every 4 hours until the second
      postoperative day. The intravenous patient-controlled analgesia group had
      significantly lower pain scores and took less time until they were able to walk
      to the bathroom, but as many side effects as the control group. We concluded that
      intravenous patient-controlled analgesia is safe and effective for pediatric
      patients who have moderate to severe pain after operations such as rib cartilage
      graft, iliac bone graft, and large flap surgeries.

PMID- 11314622
TI  - Corneal ulcers in patients with Apert syndrome.
AB  - Morbidity from corneal ulcers is often severe in patients with Apert syndrome.
      These patients are at an increased risk of developing corneal ulcers because of
      the compromised corneal environment secondary to exophthalmos. During the past 6
      years, three of five patients treated for Apert syndrome at our hospital have
      developed corneal ulcers. We present a case series discussing each patient,
      reasons for the development of ulceration, treatment, and outcomes. Morbidities
      in our group of patients included decreased visual acuity, opacified corneas,
      amblyopia, and blindness. Treatment is often difficult and complex. Therefore, an
      ophthalmologist should be an active team member in treating Apert patients.

PMID- 11314623
TI  - Optimized 3-D CT scan protocol for longitudinal morphological estimation in
      craniofacial surgery.
AB  - Frequent three-dimensional computed tomography scanning may cause deterioration
      of the lenses of the eye, which are susceptible to x-rays. The authors performed
      an experimental study using a phantom head to establish an optimized three
      dimensional computed tomography scan protocol for longitudinal morphological
      estimation in craniofacial surgery. Volume computed tomography scans were
      performed using a Hi-Speed Advantage SG CT scanner (GE Medical Systems,
      Milwaukee, WI) in the axial plane with a combination of scan parameters of varied
      values. The radiation doses induced by each scanning were measured using
      thermoluminescent dosimeter chips attached to the position of the lenses in the
      phantom. Two-dimensional images in the coronal plane and three-dimensional images
      of the osseous surface were generated from each accumulated data set. For each
      scan parameter, the images generated from data accumulated using different values
      were compared. The study showed that lens radiation dose increased with tube
      potential and was almost directly proportional to tube current and 1/pitch. The
      slice thickness did not affect lens radiation doses significantly. Images with
      good contrast resolution and low artifact level sufficient for estimating
      morphological changes were obtained using a low tube potential of 100 kVp and a
      tube current of 100 mA. In regard to z-axis spatial resolution, a slice thickness
      of less than 3 mm was required for precisely pointing out bony edges in the two
      dimensional reformation images. These results led us to conclude that volume
      computed tomography for longitudinal examination in craniofacial surgery should
      be kept to a minimum frequency and performed using a low-dose technique, small
      slice thickness, and large pitch.

PMID- 11314624
TI  - Comparison between TANIS and UICC 1997 stage grouping in parotid gland carcinoma.
AB  - To compare the correlation of T and N Integer Score (TANIS) and International
      Union Against Cancer (UICC) '97 stage grouping with survival rate in parotid
      gland carcinoma, a series of 134 patients affected by primary carcinoma of the
      parotid gland was considered in this retrospective study. Data set was classified
      according to 1997 UICC T-category and then grouped as recommended by the two
      systems. Data were analyzed by means of survival analyses (Kaplan-Meier and Cox
      algorithms). Results showed a crude survival rate of 64.9%. Univariate analysis
      by means of log-rank test yielded significant P values both for TANIS and UICC
      '97 systems (both P < 0.0001). Multivariate analysis (Cox regression adjusted for
      age and gender) showed a significant correlation between the two staging systems
      with the mortality rate. Odds ratios were 2.64 (95% CI 1.84-3.80) and 1.79 (95%
      CI 1.46-2.20) for UICC '97 and TANIS, respectively. In testing the superiority,
      UICC '97 resulted in a higher prognostic value and TANIS did not add any
      statistical contribution in determining survival. In conclusion, the new UICC
      stage grouping better defines the prognosis for cancer of the parotid gland.

PMID- 11314625
TI  - Cleft palate in a patient with Williams' syndrome.
AB  - Cleft lip or palate has not been reported in the medical literature as a part of
      Williams' syndrome. We present a patient who had cleft palate among other
      congenital manifestations. This patient's immediate postnatal period clinically
      seemed to have a Pierre Robin sequence. With the development of the craniofacial
      complex, microgenia and micrognathia with glossoptosis gradually became apparent.
      On further assessment, the patient showed other clinical findings that suggested
      a syndromic association. This required a complete evaluation to discard other
      conditions that present with low psychomotor development and distinctive facies,
      such as Kabuki syndrome or fetal alcohol syndrome. The diagnosis for Williams'
      syndrome was established based on the clinical features and supported by the
      fluorescent in situ hybridization test. Williams' syndrome has been described as
      a rare, congenital disorder characterized by physical and developmental problems.
      Common features include characteristic "elfin-like" facies, supravalvular aortic
      stenosis, hypercalcemia, low birth weight, slow weight gain, feeding problems,
      impulsive and outgoing personality, limited spatial skills and motor control, and
      intellectual disability. Although individuals with Williams' syndrome may show
      competence in areas such as language, music, and interpersonal relations, their
      IQs are usually low and they are considered moderately to mildly retarded.

PMID- 11314626
TI  - Unilateral complete cleft lip and palate repair using lip adhesion and passive
      alveolar molding appliance.
AB  - To manage a unilateral complete cleft lip and palate, lip adhesion along with the
      positioning of a passive alveolar molding appliance was performed in infants at 3
      to 6 weeks of age. The lip adhesion creates a force acting on the cleft alveolus.
      There-after, the greater segment of the alveolus is guided by the appliance,
      while the lesser segment of the alveolus is prevented from collapsing. Definite
      cheiloplasty was then performed at 5 to 6 months of age and palatoplasty at 12 to
      14 months of age. Fifteen patients with a unilateral complete cleft lip and
      palate were treated using this protocol from April 1995 to October 1998. Nine
      were female and six were male. The mean follow-up period was 13 months. The lip
      adhesion failed in one patient and was performed again 1 month later. Thirteen
      patients developed good or fair symmetrically aligned alveolar segments plus a
      symmetric platform for the nose. However, two patients developed poor maxillary
      orthopedics because of the displacement of the appliance by the patient. The
      resulting lip scar was aesthetically acceptable in most patients.

PMID- 11314627
TI  - Fractures of mandible: is spontaneous healing possible? Why? When?
AB  - Closed and open reduction of fractures of the mandible constitutes an endless
      debate, and it is interesting that modern times have not brought a conclusion to
      this controversy. From 1995 to 1997 in the Plastic Surgery Department of Argerich
      Hospital in Buenos Aires, Argentina, 23 patients were evaluated with different
      fractures of the mandible in which neither closed nor open reduction was
      performed. Seventeen patients (74%) presented associated fractures in different
      areas of the mandible and 6 (26%) only had one fracture; 2 of them (9%) were
      edentulous. Three (13%) of the 23 patients had more than two fractures in
      different areas. Condylar fractures were the only lesion in 8 patients (35%), and
      they were associated with body fractures in another 6 patients (26%). Spontaneous
      healing of the fractures occurred in all 23 patients. No complications were found
      in any of them. All fractures presented the following characteristics: 1)
      Fractured fragments were aligned without displacement (or light displacement), 2)
      Occlusion was normal (or pretraumatic occlusion), 3) Facial symmetry was
      maintained, 4) Radiography demonstrated fractures without displacement, 5) Minor
      edema and hematoma were present in the area of the fracture, and 6) There was
      only pain during masticatory movements. The treatment was as follows: 1) Soft
      food and liquid diet (solid food was avoided 30 days after trauma), 2) Opening of
      the mouth was not permitted, 3) Oral antibacterial cleaning, and 4) Analgesic
      therapy. Spontaneous healing was produced by secondary bone repair mechanism as a
      "natural" process.

PMID- 11314628
TI  - Three-dimensional facial simulations and measurements: changes of facial contour
      and units associated with facial expression.
AB  - Recent innovations in laser scanning technology provide a potentially useful
      technique for accurate three-dimensional documentation of the face. In this
      study, linear and area measurements of the facial contour and facial units have
      been recorded in a variety of chosen facial postures using surface laser scanning
      combined with three-dimensional lighting techniques on seven healthy volunteers
      and three patients with facial nerve paralysis. Three-dimensional surface
      measurement of the face was taken using a laser light scanner. Computer graphics
      lighting techniques were used to produce facial images constituted by highlights
      and shadows, which emboss facial contour and units. Then quantitative measurement
      of changes in facial angles and areas were made to analyze morphological changes
      of the face accompanying facial expression. Changes of angles and widths of the
      cheek and nasal units were found to be associated with dimensional changes
      imposed by the action of the underlying mimetic muscles. This system has
      potential value for both dynamic monitoring and evaluation of facial contour,
      units, and movement.

PMID- 11314629
TI  - Rat mandibular distraction osteogenesis: latency, rate, and rhythm determine the
      adaptive response.
AB  - Distraction osteogenesis is a well-established technique of endogenous tissue
      engineering. The biomechanical factors thought to affect the quality of the
      distraction regenerate include the latency, rate, rhythm, and consolidation
      period. In an effort to understand the impact of these parameters on regenerate
      bone formation, this study was designed to decipher the most adaptive response in
      a rat model of mandibular distraction osteogenesis. Ninety-six adult Sprague
      Dawley rats were divided into 16 subgroups (n = 6 per subgroup) based on
      variations in the distraction parameters (i.e., latency, rate, and rhythm). After
      a 28-day consolidation period, the mandibles were harvested, decalcified, and
      sectioned. A standardized histologic ranking system was used to evaluate the
      effect of each protocol on the adaptive response of the regenerate bone. In this
      study, we have demonstrated that the latency period dramatically affects the
      success of distraction osteogenesis. Furthermore, distraction rates up to 0.50 mm
      per day stimulated excellent regenerate bone formation, whereas greater
      distraction rates produced a fibrous union. Finally, higher frequency distraction
      (i.e., increased rhythm) appeared to accelerate regenerate bone formation. We
      believe that defining the critical parameters of this model will improve future
      analysis of gene expression during rat mandibular distraction osteogenesis and
      may facilitate the development of biologically based strategies designed to
      enhance regenerate bone formation.

PMID- 11314630
TI  - Osteoblast gene expression is differentially regulated by TGF-beta isoforms.
AB  - The transforming growth factor beta (TGF-beta) superfamily encompasses a number
      of important growth factors including several TGF-beta isoforms, the bone
      morphogenetic proteins, activins, inhibins, and growth and differentiation
      factors. TGF-beta 1, -beta 2, and -beta 3 are three closely related isoforms that
      are widely expressed during skeletal morphogenesis and bone repair. Numerous
      studies suggest that each isoform has unique in vivo functions; however, the
      effects of these TGF-beta isoforms on osteoblast gene expression and maturation
      have never been directly compared. In the current study, we treated
      undifferentiated neonatal rat calvaria osteoblast-enriched cell cultures with 2.5
      ng/ml of each TGF-beta isoform and analyzed gene expression at 0, 3, 6, and 24
      hours. We demonstrated unique isoform-specific regulation of endogenous TGF-beta
      1 and type I collagen mRNA transcription. To assess the effects of extended TGF
      beta treatment on osteoblast maturation, we differentiated osteoblast cultures in
      the presence of 2.5 ng/ml of each TGF-beta isoform. Analysis of collagen I,
      alkaline phosphatase, and osteocalcin demonstrated that each TGF-beta isoform
      uniquely suppressed the transcription of these osteoblast differentiation
      markers. Interestingly, TGF-beta isoform treatment increased osteopontin
      expression in primary osteoblasts after 4 and 10 days of differentiation. To our
      knowledge, these data provide the first direct comparison of the effects of the
      TGF-beta isoforms on osteoblast gene expression in vitro. Furthermore, these data
      suggest that TGF-beta isoforms may exert their unique in vivo effects by
      differentially regulating osteoblast cytokine secretion, extracellular matrix
      production, and the rate of cellular maturation.

PMID- 11314631
TI  - Effects of synthetic craniofacial materials on cerebral microcirculation.
AB  - Four groups were studied to look at effects of synthetic materials on the pial
      vasculature. Using Sprague-Dawley rats, an open pial window approach was used in
      which there was a control group, a hydroxyapatite cement group mixed with sodium
      phosphate, a methylmethacrylate slow-set, and a methylmethacrylate fast-set
      group. There were 10 animals with 20 vessels studied within each group. The
      permeability leakage outside the vessel was evaluated to determine the vascular
      albumin leakage, and the number of rolling and adherent leukocytes was studied
      within each group. It was seen that the control group was significantly different
      compared with the fast-set methylmethacrylate group during a 2-hour period in
      regard to the percentage leakage, as well as a number of rolling and adherent
      leukocytes. This is one of the first studies to demonstrate the effects of
      synthetic craniofacial materials on the underlying pial vasculature.

PMID- 11314632
TI  - Klippel-Trenaunay-Weber syndrome with hemimegalencephaly.
AB  - There are many documented cases of Klippel-Trenaunay-Weber syndrome characterized
      by the triad of port wine stain, varicose veins, and hypertrophy of bones and
      overlying tissue. A few cases have even included the additional findings of
      hemimegalencephaly. We report a case of Klippel-Trenaunay-Weber syndrome with
      hemimegalencephaly and calvarial hypertrophy, but no evidence of limb or trunk
      hypertrophy.

PMID- 11314634
TI  - It's a challenge.

PMID- 11314633
TI  - Re: Regeneration of the sagittal suture by GTR and its impact on growth of the
      cranial vault.

PMID- 11314635
TI  - Insulin resistance linked to periodontal disease.

PMID- 11314636
TI  - Breast cancer: snuff said.

PMID- 11314637
TI  - Back pain may be a state of mind.

PMID- 11314638
TI  - Pancreas transplants aiding persons with diabetic nephropathy.

PMID- 11314639
TI  - Utilization of local anesthesia by Arkansas dental hygienists, and dentists'
      delegation/satisfaction relative to this function.
AB  - PURPOSE: Given the legalization of administration of local anesthesia as an
      expanded function for dental hygienists in Arkansas, the purpose of this study
      was to 1) describe the utilization of local anesthesia in dental hygiene care; 2)
      compare the utilization of local anesthesia by dental hygienists certified in the
      administration of local anesthesia and those who were not; 3) determine if there
      was a difference in attitude toward the use of local anesthesia for dental
      hygiene procedures between dental hygienists certified in the expanded function
      versus those not certified; 4) determine if and to what degree employers delegate
      this procedure to certified employees; and 5) compare employer satisfaction with
      this expanded function for those who employed a certified dental hygienist and
      those who did not. METHODS: Surveys were sent to all Arkansas dental hygienists
      certified, as of June 1998, to administer local anesthesia as well as an equal
      random sample of Arkansas dental hygienists not certified in the expanded
      function. The dentist employers of these dental hygienists also were asked to
      complete a companion survey. These surveys included demographic items as well as
      questions about the demand for and utilization of local anesthesia by dental
      hygienists. Additionally, the surveys included an opinionnaire section concerning
      attitudes toward and perceptions of the administration of local anesthesia by
      dental hygienists. RESULTS: An overall response rate of 31% (n = 182) was
      achieved for the survey of the dental hygienist sample (n = 580). Forty-one
      percent of the surveys (n = 118) were returned by the dental hygienists certified
      in the administration of local anesthesia, while 22% (n = 64) of the surveys were
      returned by those not certified in the function. An approximate response rate of
      25% (n = 146) was achieved for the surveys of the dentist employers. Findings
      indicate that the respondents perceived local anesthesia as beneficial for both
      dental hygiene patients and clinicians. Arkansas dental hygienists and dentists
      reported that this function had a positive impact on scheduling, production,
      patient satisfaction and comfort, and quality of care. Furthermore, more than
      nine out of 10 of the dentist respondents were satisfied with their dental
      hygienists local anesthesia skills and/or would encourage their uncertified
      dental hygienists to become certified. Dental hygienists certified in the
      function reported utilizing this technique moderately to fully for patient care,
      particularly for those in practices with greater numbers of periodontally
      involved patients. Certified dental hygienists also viewed local anesthesia as
      contributing to the quality of patient care and necessary for dental hygiene
      procedures. CONCLUSIONS: Results of this study provide evidence that local
      anesthesia benefits dental hygiene patients and clinicians. Both Arkansas dental
      hygienists and dentists viewed this expanded function as necessary for provision
      of quality dental hygiene care. The dentist employers of certified dental
      hygienists reported that the function had a positive impact on scheduling,
      production, patient satisfaction and comfort, and quality of care.

PMID- 11314640
TI  - Improving the oral hygiene of institutionalized mentally retarded clients.
AB  - PURPOSE: The quality of oral health care of persons with mental retardation has
      been reported in the literature to be less than that of their normal peers. The
      purpose of this study, set in a Midwest institution for persons with
      developmental retardation, was to determine if a change in policy followed by
      staff training and monitored by an interested third party would improve the oral
      hygiene of clients living on wards. METHODS: Methods used to train staff in
      proper toothbrushing were developed. Three living units were randomly selected
      for study: control, training plus accountability (experimental group I), and
      training without accountability (experimental group II). The direct care staff of
      both experimental groups were trained in proper toothbrushing techniques. Staff
      of the control group received no training. A dental hygienist visited the living
      unit periodically to evaluate and provide feedback on the plaque index scores
      taken by the caregivers in both experimental groups. RESULTS: The plaque indexes
      of group I showed significant improvement over the control group and group II.
      CONCLUSION: The results of this pilot study support the other findings of higher
      plaque indexes for residents with mental retardation and that modifying
      toothbrushing policies and staff training are not as critical to the improvement
      of the clients' oral hygiene as is the presence of an involved, interested third
      party.

PMID- 11314642
TI  - Career satisfaction and job characteristics of dental hygiene master's degree
      graduates.
AB  - PURPOSE: The primary objectives of this study were to assess career and degree
      satisfaction as well as job characteristics of individuals graduating from
      programs awarding the master of science in dental hygiene or dental hygiene
      education degree. METHODS: A pilot-tested questionnaire was mailed to all 252
      individuals who graduated between 1980 and 1995 from eight dental hygiene
      master's degree programs (MSDH). The questionnaire included both closed- and open
      ended items regarding career history/career path, career satisfaction,
      professional involvement, and opinions/perceptions about the graduate program the
      participant attended. Responses were analyzed using descriptive statistics and
      two-way tables. RESULTS: After three complete mailings, the response rate was 69%
      (n = 174). The majority of respondents reported currently working approximately
      five days per week (54%), with 62% having annual salaries over $40,000. Eighty
      six percent were satisfied overall with their career choices, although 30% stated
      that they would not pursue the same degree again. CONCLUSION: Overall, graduates
      from MSDH programs are satisfied with their degree choice as well as the
      opportunities it has afforded them. These findings serve to expand the knowledge
      base of graduate dental hygiene education and of the graduates from these
      programs as well as provide suggestions for improvement to graduate dental
      hygiene programs.

PMID- 11314641
TI  - Ten years of patients' experiences with fixed implant-supported prostheses.
AB  - PURPOSE: This study investigated patients' perceptions of fixed implant-supported
      prostheses (ISP) in totally edentulous jaws in order to obtain a broader base for
      patient information. METHODS: A total of 135 patients who had received prosthetic
      rehabilitation treatment responded to a questionnaire on oral functions, speech,
      oral self-care, esthetics, lifestyle changes and self-confidence, oral comfort,
      and overall satisfaction with ISP. The patients also listed positive and negative
      experiences with the ISP. RESULTS: Most patients (97%) reported overall
      satisfaction. Chewing ability was rated as good or very good by all but one
      (99.3%). Twenty-six patients (19.6%) identified bruxing and clenching habits,
      these were significantly younger than those free from problems. Phonetic problems
      were reported by 32.8% after insertion, with 18.6% (eight patients) having
      remaining problems after seven to 10 years. Most of the patients (87.2%) found it
      easy to clean the prosthesis. Improved lifestyle after ISP insertion was reported
      by 75% and increased self-confidence by 82% of the patients. Improvements were
      especially perceptible in social situations that involved conversation or eating.
      None of the measured variables was related to duration of having ISP.
      CONCLUSIONS: The patients' experiences in this study lasted over a period of 10
      years, thus their positive and negative aspects can serve as information support
      for dentistry to enable future ISP patients to make appropriate choices. The
      information could be made available to patients by including in a patient
      targeted booklet.

PMID- 11314643
TI  - Application of the human needs conceptual model to dental hygiene practice.
AB  - The Human Needs Conceptual Model is relevant to dental hygiene because of the
      need for dental hygienists to be client focused, humanistic, and accountable in
      practice. Application of the Human Needs Conceptual Model provides a formal
      framework for identifying and understanding the unique needs of the client that
      can be met through dental hygiene care. Practitioners find that the Human Needs
      Conceptual Model can not only help them in assessment and diagnosis, but also in
      client education, decision-making, care implementation, and the evaluation of
      treatment outcomes. By using the model, the dental hygienist is able to manage
      client care humanistically and holistically, and ensure that care is client
      centered rather than task-oriented. With the model, a professional practice can
      be made operational.

PMID- 11314644
TI  - [Distant informational interactions in bacteria].
AB  - Exchange of information between bacteria via physical signals, referred to as
      "distant interactions" (DI), is the subject of this review. All cases of DI
      reported to date are discussed, as well as the history of these studies and the
      place of DI in bacterial communication. Bacterial DI are a particular case of DI
      occurring in nature (in plants, animals, and fungi). Along with the chemical
      signals of intracellular communications, DI play a significant role in the life
      of microorganisms, especially during critical periods.

PMID- 11314645
TI  - [About different mechanisms of the biochemical adaptation of mycelial fungi to
      temperature stress: changes in cytosol carbohydrate composition].
AB  - The effect of temperature stress on the cytosol carbohydrate composition of fungi
      belonging to various systematic groups was investigated. In Mucorales
      representatives (subkingdom Eomycota, phylum Archemycota, class Zygomycetes),
      adaptation to hypo- and hyperthermia occurs via the regulation of trehalose
      synthesis, although inositol is also involved in these processes in Blakeslea
      trispora. Basidiomycota (subkingdom Neomycota) use two pathways of biochemical
      adaptation, depending on the cytosol carbohydrate composition. In the absence of
      sucrose, glycerol and arabitol are involved in the adaptation to hyperthermia;
      trehalose accumulates under hypothermic conditions (type I of regulation). Type
      II regulation (revealed in Pleurotus ostreatus) involves sucrose rather than
      glycerol or arabitol. The data obtained are discussed in terms of fungal
      systematics and phylogeny.

PMID- 11314646
TI  - [About different mechanisms of the biochemical adaptation of mycelial fungi to
      temperature stress: changes in lipids composition].
AB  - A comparative study was conducted concerning the effect of temperature stress on
      the lipid composition of representatives of the subkingdoms Eomycota and
      Neomycota. Changes in the composition of lipid acyl chains (such as saturation
      and desaturation, isomerization, and changes in the length of fatty acid carbon
      chains), in the phospholipid composition, and in the contents of sterols and
      other neutral lipids were revealed. Hyperthermia resulted in (i) an increase in
      the phosphatidylcholine level; (ii) a decrease in the phosphatidylethanolamine
      level; (iii) a rise in the content of reserve lipids (triacylglycerols); and (iv)
      a decline in the free fatty acid level in the neutral lipids. An inverse pattern
      occurred under hypothermic conditions. The peculiarities in the patterns of the
      temperature adaptation-related changes in the lipid bilayer composition are
      considered in terms of the systematic position of the fungi.

PMID- 11314647
TI  - [Interaction of bacteria with mercuric compounds].
AB  - We investigated the interaction of mercuric compounds with the bacteria
      Corynebacterium ammoniagenes, Micrococcus luteus, and Mycobacterium smegmatus
      capable of producing hydroxylamines (R-NOH) and 2-C-methyl-D-erythritol-2,4
      cyclopyrophosphate (MECP), which are prone to form free radicals. The interaction
      of these substances with Hg2+ ions and their dynamics during the mercuric
      poisoning of bacteria was studied by EPR and NMR. Under stress conditions induced
      by lowering pH or generation of active oxygen species, the bacteria and,
      especially, their mutants with enhanced sensitivity to oxidative stress, were
      found to respond to exposure to 1-3 micrograms/ml HgCl2 and p
      chloromercuribenzoate by a several-fold increase in their viability. The data
      obtained were interpreted in terms of the involvement of the sulfhydryl groups of
      bacterial surface proteins in this phenomenon. The interaction of bacteria with
      mercuric compounds may affect the pathogenesis of tuberculosis and other
      diseases.

PMID- 11314648
TI  - [Extracellular factors of adaptation of Pneudomonas fluorescens batch cultures to
      adverse conditions].
AB  - The culture liquid filtrate of an exponential-phase Pseudomonas fluorescens batch
      culture added to another P. fluorescens culture at the moment of inoculation was
      found (1) to prevent or diminish cell adsorption of the flask walls; (2) to
      enhance the intensity of cell respiration; (3) to shorten the period of
      adaptation of LB-grown cells to growth in glucose-containing mineral M9 medium;
      (4) to stimulate bacterial growth at supraoptimum temperature (36 degrees C) and
      pH values (4.8 and 9.2); and (5) to decrease the death rate of bacteria at the
      supraoptimum growth temperature. These results were interpreted as indicating
      that P. fluorescens cultures produce two types of regulatory exometabolites
      similar to those revealed earlier in Escherichia coli and Bacillus subtilis
      cultures: the direct-action adaptogenic factor XI capable of increasing bacterial
      resistance to unfavorable growth conditions (temperature and pH) and factor
      promoting adaptation to new media. Both factors are presumably low-molecular
      weight hydrophilic nonprotein compounds.

PMID- 11314649
TI  - [Effect of exogenous sterols on the growth and fatty acid composition of the
      oomycete Pythium debaryanum].
AB  - Exogenous ergosterol and cholesterol were found to affect the growth and
      lipogenesis of the oomycete fungus Pythium debaryanum, which is unable to
      synthesize de novo steroid compounds. These sterols stimulated the growth of the
      fungus during its submerged cultivation in glucose-peptone medium. This was
      accompanied by the shortening of the lag phase, the lengthening of the period of
      active growth, and by a 3.7- or 4.3-fold increase in the maximum biomass in
      response to the addition of ergosterol or cholesterol, respectively. In the
      presence of ergosterol, the cellular content of polyenoic fatty acids increased,
      and the relative content of eicosapolyenoic fatty acids reached 31.4% of the
      total amount of fatty acids in cells. Conversely, cholesterol decreased the
      cellular content of polyenoic acids, and the relative content of eicosapolyenoic
      acids fell to 19.6% of the total amount of fatty acids. It may be inferred that
      exogenous sterols enhance the yield of pharmacologically active polyenoic acids
      because of the growth stimulation.

PMID- 11314650
TI  - [Effect on microelements on biosynthes of secondary metabolites in the fungus
      Penicillium citrinum Thom VKM F-1079].
AB  - Penicillium citrinum VKM F-1079 was found to produce clavine ergot alkaloids and
      citrinin, a secondary O-heterocyclic metabolite. Citrinin was produced in the
      idiophase, whereas the production of ergot alkaloids paralleled fungal growth.
      The addition of manganese ions to the growth medium stimulated the biosynthesis
      of both citrinin and ergot alkaloids. Zinc ions stimulated only citrinin
      synthesis. The presence of these microelements in the growth medium influenced
      the proportion between the ergot alkaloids synthesized. Copper, manganese, and
      iron ions affected but little fungal growth and alkaloid production. The effect
      of microelements on the main kinetic parameters of growth and alkaloid production
      was studied.

PMID- 11314651
TI  - [Comparative study of xylose(glucose) isomerase synthesis in Arthrobacter
      strains].
AB  - The substrate specificity of isomerases produced by six strains of Arthrobacter
      sp. was studied. The role of utilizable carbon sources in controlling enzyme
      biosynthesis was established. All of the strains studied were found to produce
      xylose isomerases efficiently, converting D-xylose into D-xylulose and D-glucose
      into D-fructose. All but A. ureafaciens B-6 strains showed low activity toward D
      ribose, Arthrobacter sp. B-5 was slightly active toward L-arabinose, and A.
      ureafaciens B-6 and Arthrobacter sp. B-2239, toward L-rhamnose. In Arthrobacter
      sp. B-5, the synthesis of xylose/glucose isomerase was constitutive (i.e., it was
      not suppressed by readily metabolizable carbon sources). The synthesis of
      xylose/glucose isomerase induced by D-xylose in Arthrobacter sp. strains B-2239,
      B-2240, B-2241, and B-2242 and by D-xylose and xylitol in A. ureafaciens B-6 was
      suppressed by readily metabolizable carbon sources in a concentration-dependent
      manner. The data obtained suggest that D-xylose and/or its metabolites are
      involved in the regulation of xylose/glucose isomerase synthesis in the
      Arthrobacter sp. strains B-5, B-2239, B-2240, and B-2241.

PMID- 11314652
TI  - [Medium for the production of Bacillus intermedius glutamyl endopeptidase by the
      recombinant Bacillus subtilis].
AB  - A nutrient medium was elaborated for the efficient production of glutamyl
      endopeptidase by the recombinant Bacillus subtilis strain AJ73 bearing the
      Bacillus intermedius 3-19 glutamyl endopeptidase gene within a multicopy plasmid.
      Optimal concentrations of the main nutrients, peptone and inorganic phosphate,
      were found using a multifactor approach. To provide for active growth and
      efficient glutamyl endopeptidase production, the cultivation medium of the
      recombinant strain should be enriched in phosphorus, organic and inorganic
      nitrogen sources, and yeast extract. Complex protein substrates, such as casein
      and gelatin, enhanced the biosynthesis of glutamyl endopeptidase. At the same
      time, easily metabolizable carbon sources suppressed it. The production of
      glutamyl endopeptidase was stimulated by the bivalent cations Ca2+, Mg2+, and
      Co2+.

PMID- 11314653
TI  - [Localization of proteolytic enzymes in cells of Bacillus intermedius].
AB  - The activities of proteinases in the culture fluid and cellular fractions of
      Bacillus intermedius 3-19 grown under various conditions were studied. Thiol
      dependent serine proteinase was the prevalent enzyme in the total pool of
      extracellular proteinases (70%); its catalytically active form was also detected
      in the cell membrane and, during active enzyme production, in the cell wall.
      Another enzyme, glutamyl endopeptidase (10% of the total pool), was detected in
      the cell membrane; it was also found in the cell wall and cytoplasm during active
      enzyme secretion into the growth medium. Production of these enzymes was maximal
      on medium containing inorganic phosphate and gelatin and decreased 2- to 4-fold
      on medium with glucose and lactate. The level of activity of extracellular
      enzymes correlated with that of corresponding membrane-bound proteins. The
      addition of CoCl2 (2 mM) into the medium caused an essential increase in
      extracellular glutamyl endopeptidase activity and promoted the release of the
      membrane-bound enzyme into the culture fluid. Proteolytic activity towards casein
      was also detected in the cytoplasm. The proteinases localized in the cytoplasm
      were shown to differ in their properties from those secreted.

PMID- 11314654
TI  - Restricted wobble rules for eukaryotic genomes.

PMID- 11314655
TI  - Describing recombination.

PMID- 11314656
TI  - Bibliography of toxinology.

PMID- 11314657
TI  - ANA celebrates Senate passage of needlestick prevention legislation.

PMID- 11314658
TI  - Teenagers' perceived access to primary health care.

PMID- 11314659
TI  - Are perforator flaps truly more cost-effective than TRAM flaps? How good is the
      evidence.

PMID- 11314660
TI  - Comparison of the costs of DIEP and TRAM flaps.

PMID- 11314661
TI  - Merocel use as an adjunct for tie-over dressing.

PMID- 11314662
TI  - Postrhinoplasty mucous cyst of the nose.

PMID- 11314663
TI  - Parotid gland fistula: treatment with botulinum toxin.

PMID- 11314664
TI  - The search for the youthful upper lip using laser resurfacing.

PMID- 11314665
TI  - A new interpretation of the facies of an Italian carnival mask.

PMID- 11314666
TI  - Treatment of persistent lymphorrhea using bleomycin sclerotherapy.

PMID- 11314667
TI  - Surgical treatment of anal stenosis following perineal shotgun injury.

PMID- 11314668
TI  - Limiting the damage of iatrogenic extravasation injury in neonates.

PMID- 11314669
TI  - Flap vascularity after free musculocutaneous tissue transfer.

PMID- 11314670
TI  - Simple method to remove clots from a suction drain tube.

PMID- 11314672
TI  - Converting to digital photography.

PMID- 11314671
TI  - Scar formation in young and aged rabbits.

PMID- 11314673
TI  - Transmembrane signaling through phospholipase C in cortical and hippocampal
      membranes of psychogenetically selected rat lines.
AB  - RATIONALE: One of the major pathways for neurotransmitter signaling involves
      phosphoinositide-specific and G-protein-dependent phospholipase C-beta (PLC
      beta), which stimulates the formation of inositol 1,4,5-trisphosphate and
      diacylglycerol. Serotonergic and muscarinic-cholinergic signals in the brain are
      largely mediated through the hydrolysis of phosphoinositides by PLC. OBJECTIVES:
      The aim of the experiments reported here was to explore the potential differences
      in neurotransmitter receptor coupling to PLC in Roman high-avoidance (RHA)/Verh
      and Roman low-avoidance (RLA)/Verh rats, by examining the changes in agonist
      (carbachol, 5-methyltryptamine)-stimulated phosphoinositide hydrolysis in
      hippocampal and cortical membranes derived from the two rat lines. METHODS: To
      investigate changes in receptor and G-protein coupling to PLC in the brains of
      these two psychogenetically selected rat lines, which differ in their emotional
      profiles/learning abilities, we examined GTPgammaS-, agonist (carbachol, 5
      methyltryptamine)-, and calcium-stimulated phosphoinositide hydrolysis in
      cortical and hippocampal membranes of RHA/Verh and RLA/Verh rats. RESULTS: The
      results indicated that calcium-induced increase in PLC activity was larger in the
      cortex and hippocampus of RHA/Ver rats, as compared to their RLA/Verh
      counterparts. Conversely, GTPgammaS- and agonist-induced PLC activity was less
      pronounced in the hippocampus of RHA/Verh with respect to RLA/Verh rats. Western
      blot analysis showed no significant differences in the relative values of the G
      proteins alphaq/11 and betagamma subunits between both groups of rats in any
      brain region. However, the levels of PLC-beta1, PLC-beta3, and PLC-beta4 were
      significantly lower in the hippocampus of RHA/Verh than in RLA/Verh rats.
      CONCLUSIONS: It is concluded that the hippocampus of RHA/Verh rats has severe
      deficiencies in PLC activity stimulated by guanine nucleotides and agonists,
      which are specifically related to a lower level of expression of the PLC-beta
      type isozymes, a fact that may account for the differential behavioral phenotype
      observed in these psychogenetically selected rat lines.

PMID- 11314674
TI  - Effects of MK-801 and nicotine combinations on memory consolidation in CD1 mice.
AB  - RATIONALE: Recent experiments have shown that pre-trial administrations of
      nicotine to rats tested in a 16-arm radial maze attenuated the MK-801-induced
      deficit in both working and reference memory performance. Memory consolidation
      can be influenced in laboratory animals, by post-training administration of
      drugs. OBJECTIVE: In the present study we have investigated the effects on memory
      consolidation of CD1 mice exerted by: a) the non-competitive N-methyl-D-aspartate
      (NMDA) receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo
      [a,d]cyclo-hepten-5, 10-imine-maleate] b) nicotine, and c) combinations of MK-801
      and nicotine. METHODS: Different groups of mice were injected intraperitoneally
      (IP) with the single drugs and with their combinations, immediately after
      training in a passive avoidance task. Additional groups of animals were also
      injected 2 h post-training with the highest effective dose of MK-801 (0.3 mg/kg),
      with the highest effective dose of nicotine (0.5 mg/kg) or with the combination
      of an otherwise ineffective dose of MK-801 (0.1 mg/kg) with the highest effective
      dose of nicotine, respectively. Their performances were compared with those of
      mice injected with saline, with the vehicle of nicotine and with the other
      treatment combinations, respectively RESULTS: The results showed that MK-801
      exerted deleterious effects, while nicotine exerted facilitatory effects on mice
      performances. Further, an otherwise ineffective dose of MK-801 (0.1 mg/kg)
      antagonized the facilitatory effects of nicotine (0.25 and 0.5 mg/kg). In the 2 h
      post-training injected groups the treatments were ineffective, showing that the
      immediate post-training drug administrations affected memory consolidation
      processes. CONCLUSIONS: In conclusion, from the present research, it is evident
      that NMDA glutamate and nicotinic acetylcholine receptor systems interact in
      modulating memory consolidation in CD I mice.

PMID- 11314675
TI  - Differential tolerance to antinociceptive effects of mu opioids during repeated
      treatment with etonitazene, morphine, or buprenorphine in rats.
AB  - RATIONALE: Repeated treatment experiments with high and low efficacy agonists
      provide critical insight into possible mechanisms underlying development of
      opioid tolerance. OBJECTIVE: Experiments in a tail-withdrawal assay tested the
      hypothesis that magnitude of tolerance to antinociceptive effects is inversely
      related to agonist relative efficacy in rats intermittently treated with
      etonitazene. morphine, or buprenorphine. METHODS: The antinociceptive effects of
      five mu opioid agonists were tested in male, Sprague-Dawley rats in a warm-water
      tail-withdrawal assay. To induce tolerance, escalating doses of the higher
      efficacy agonist etonitazene, the high efficacy agonist morphine, or the lower
      efficacy agonist buprenorphine were administered twice daily for 2-8 weeks.
      RESULTS: Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 [(1)-beta
      2'-hydroxy-2,9-dimethyl-5-phenyl-6,7-benzomorphan] produced dose-dependent
      increases in tail-withdrawal latency until 100% maximum possible effect (%MPE)
      was obtained. Treatment with escalating doses of etonitazene, morphine, or
      buprenorphine produced greater tolerance to the lower efficacy agonists
      buprenorphine and GPA 1657 than to the higher efficacy agonists etonitazene,
      etorphine, and morphine. Treatment with buprenorphine, a lower efficacy agonist,
      produced greater tolerance than did treatment with equivalent doses of the higher
      efficacy agonists morphine or etonitazene. CONCLUSIONS: Taken together, these
      data suggest that magnitude of antinociceptive tolerance is inversely related to
      relative efficacy of mu agonists, with lower efficacy agonists being more
      susceptible to tolerance than are higher efficacy agonists under these
      intermittent dosing conditions.

PMID- 11314676
TI  - Reinforcing effects of oral cocaine: contextual determinants.
AB  - RATIONALE: Although the behavioral, subjective, and physiological effects of oral
      cocaine have been investigated, its reinforcing effects have not been
      demonstrated. OBJECTIVE: The primary aims of this study were to examine the
      reinforcing effects of oral cocaine and determine whether such effects can be
      influenced by manipulating behavioral requirements following drug ingestion.
      METHODS: Nine adult volunteers with histories of cocaine abuse were trained to
      discriminate between orally administered cocaine (100 mg/70 kg) and placebo
      capsules under double-blind conditions. Following acquisition of cocaine vs
      placebo discrimination (80% correct), the reinforcing effects of cocaine were
      determined using two different choice conditions (dependent and independent).
      Volunteers were first exposed to cocaine and placebo once each with a relaxation
      activity (sitting in a cushioned chair) and a vigilance activity (performing a
      computer task). Following exposure to each drug with each activity, volunteers
      began the dependent choice condition. Every 2 days volunteers chose which drug
      (cocaine or placebo) they ingested with the vigilance and relaxation activities.
      Volunteers could not choose the same drug with both activities. This procedure
      occurred 5 times over a 10-day period. The independent choice condition took
      place over 2 days. On one day, volunteers chose which drug (cocaine or placebo)
      they ingested with the relaxation activity and, on the other day (in
      counterbalanced order), which drug they ingested with the vigilance activity.
      Volunteers were allowed to select the same drug with both activities. RESULTS:
      All volunteers successfully acquired the cocaine vs placebo discrimination. In
      the dependent choice condition, all volunteers significantly chose cocaine over
      placebo with the vigilance activity and chose placebo over cocaine with the
      relaxation activity. In the independent choice condition, volunteers
      significantly chose cocaine over placebo with the vigilance activity (i.e.,
      cocaine functioned as a positive reinforcer in the vigilance context).
      Interestingly, the independent choice condition also showed that volunteers chose
      placebo over cocaine with the relaxation activity (i.e., cocaine functioned as a
      negative reinforcer because it was avoided relative to placebo). CONCLUSION: The
      study shows that the behavioral requirements following drug ingestion can be a
      determinant of whether or not oral cocaine functions as a reinforcer in
      volunteers with histories of cocaine abuse.

PMID- 11314677
TI  - Effects of methadone on cognition, mood and craving in detoxifying opiate
      addicts: a dose-response study.
AB  - RATIONALE: Methadone is the most widespread pharmacological treatment for opiate
      dependency but relatively little is known of its effects on cognitive and
      psychomotor functioning, drug craving and mood. OBJECTIVE: The present study
      aimed to assess the acute effects of methadone in patients admitted to an opiate
      detoxification programme. METHODS: Patients were randomly allocated to one of two
      groups who received either 50% or 100% of their daily stabilisation dose, and a
      placebo, in a double-blind, cross-over design. Twenty patients completed the
      study, all were assessed pre- and post-drug on 2 separate testing days. RESULTS:
      Performance on a task tapping episodic memory (delayed recall of a prose passage)
      was significantly impaired following the 100% daily dose of methadone. Methadone
      treatment had no effect on craving or mood. Patients were unable to distinguish
      between methadone and placebo treatments. CONCLUSIONS: A single dose of methadone
      can induce episodic memory impairment in patients who have a history of heroin
      use averaging more than 10 years. Such impairment can be avoided by giving
      methadone in divided doses.

PMID- 11314678
TI  - Gender differences in the subjective effects of MDMA.
AB  - RATIONALE: 3.4-Methylenedioxymethamphetamine (MDMA) mainly releases serotonin (5
      HT) and is contained in the recreational drug Ecstasy. 5-HT is known to play an
      important role in mood and anxiety disorders, for which there is a female
      preponderance. To date, there are no systematic data on gender differences in the
      subjective effects of MDMA. OBJECTIVES: The present work analyzed the pooled data
      from three controlled studies on the psychological and physiological effects of
      MDMA in healthy volunteers with no or minimal MDMA experience. A particular focus
      of the analyses were possible gender differences. METHODS: A total of 74 subjects
      (54 male, 20 female) participated in all three studies. MDMA in oral doses
      ranging from 70-150 mg (1.35-1.8 mg/kg) was administered under double-blind
      placebo-controlled conditions. Subjective peak changes were assessed by
      standardized psychometric rating scales. Physiological measures were blood
      pressure, heart rate, and peripheral body temperature. Adverse drug effects were
      assessed during the experimental session and after 24 h. RESULTS: Psychoactive
      effects of MDMA were more intense in women than in men. Women especially had
      higher scores for MDMA-induced perceptual changes, thought disturbances, and fear
      of loss of body control. The dose of MDMA positively correlated with the
      intensity of perceptual changes in women. Acute adverse effects and sequelae were
      also more frequent in female than in male subjects. In contrast, men showed
      higher increases in blood pressure than woman. CONCLUSIONS: The fact that equal
      doses of MDMA per kilogram body weight produce stronger responses in women
      compared to men is consistent with an increased susceptibility of women to the 5
      HT-releasing effects of MDMA. Our results also indicate that increasing doses of
      MDMA produce more hallucinogen-like perceptual alterations, particularly in
      women.

PMID- 11314679
TI  - The differential effects of prenatal stress in rats on the acoustic startle
      reflex under baseline conditions and in response to anxiogenic drugs.
AB  - RATIONALE: The prenatal stress syndrome (PS) is characterized by exaggerated
      behavioral and physiological responses to stressful stimuli and anxiogenic
      agents. OBJECTIVES: To characterize the behavioral effects of PS on the acoustic
      startle reflex (ASR) and to determine the possible role of PS-induced alterations
      in noradrenergic control of ASR by determining the effects of the alpha2
      adrenoceptor antagonists, yohimbine, idazoxan, and RS79948-197. METHODS: PS was
      induced by exposing pregnant dams to a mild stressor of handling and saline
      injection (0.1 ml, s.c.) from gestational days 14 to 21. Control dams were left
      undisturbed throughout pregnancy. Using adult male offspring, all ASR studies
      consisted of either a 30- or 60-min testing period containing 60 or 120 acoustic
      startle stimuli trials (95 dB, 50 ms noise burst) at a fixed intertrial interval
      of 30 s after a 5-min acclimation period. For drug studies, a 3-day repeated
      measures design was implemented. RESULTS: With the exception of the response to
      the first startle stimulus on the first day of testing, there were no significant
      differences in baseline ASR between control and PS offspring. Low doses of
      yohimbine, idazoxan, and RS79948-197 were anxiogenic in the ASR test in both
      control and PS offspring. PS offspring were less responsive to higher doses of
      yohimbine (5 mg/kg) and idazoxan (8 mg/kg) but did not differ from control in
      their responses to any dose of RS79948-197. CONCLUSIONS: Anxiogenic effects of
      yohimbine, idazoxan, and RS79978-197, likely mediated via alpha2-adrenoceptor
      blockade, are similar in control and PS rats. Differences between control and PS
      rats occurred in the response to higher doses of yohimbine and idazoxan. Non
      specific effects of these drugs, such as actions at 5HT1A receptors, may cause
      their behavioral profile to be altered by PS, and to differ from the highly
      selective RS79948-197.

PMID- 11314680
TI  - Modulation of MK-801-induced behaviour by noradrenergic agents in mice.
AB  - RATIONALE: Inhibition of glutamatergic N-methyl-D-aspartate (NMDA) receptors
      following the administration of NMDA receptor antagonists results in psychotic
      like behaviour. Whereas it is known that pharmacological manipulation of
      dopaminergic and serotonergic pathways affect this drug-induced psychosis, a role
      for noradrenaline has not yet been clearly defined. OBJECTIVES: Thus, in the
      present study, we assessed a possible role for noradrenaline in the behavioural
      response to the non-competitive NMDA receptor anatgonist, MK-801, in male CD-I
      mice. RESULTS: MK-801 (0.02-1.28 mg/kg; ED50 0.2 mg/kg; s.c.) induced a dose
      dependent increase in locomotor, stereotypic and ataxic behaviours. Pre-treatment
      with the noradrenaline re-uptake inhibitors, desipramine (10 mg/kg; i.p.) and
      reboxetine (20 mg/kg; i.p.), attenuated the locomotor, stereotypic and ataxic
      response to MK-801 (0.2 mg/kg; s.c.). The noradrenergic system was lesioned with
      N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, 50 mg/kg;
      i.p., 7 and 4 days prior to challenge) to reduce noradrenaline concentrations in
      the cortex by 70%-80%. Whereas DSP-4 lesioning had little effect on the response
      to MK-801, it completely reversed the attenuating effects of reboxetine. Pre
      treatment with the alpha2 adrenoceptor agonist, clonidine (0.2 mg/kg; i.p.), and
      the antagonist, yohimbine (2 mg/kg; i.p.), attenuated and potentiated the
      response to MK-801, respectively. Pre-treatment with the alpha1 adrenoceptor
      antagonist, prazosin (2 mg/kg; i.p.), reduced the MK-801-induced response.
      CONCLUSIONS: It therefore appears that presynaptic noradrenergic alpha2 and
      postsynaptic alpha1 adrenoceptor stimulation exert opposing effects on the
      behavioural expression of MK-801 in mice.

PMID- 11314681
TI  - Subchronic effects of the GABA-agonist lorazepam and the 5-HT2A/2C antagonist
      ritanserin on driving performance, slow wave sleep and daytime sleepiness in
      healthy volunteers.
AB  - RATIONALE: Lorazepam, a benzodiazepine anxiolytic, may increase daytime
      sleepiness and impair psychomotor performance, which is hazardous for patients
      engaging in daily activities such as car driving. Given current prescription
      practice, information on the repeated dose effects is required. The 5-HT2A/2C
      antagonist ritanserin was originally developed as a safer alternative to the
      benzodiazepines, yet having limited clinical efficacy. 5HT2A/2C receptors have
      been implicated in regulating slow-wave sleep but little is known about their
      role in human performance. OBJECTIVE: The present study investigated the
      subchronic effects of the benzodiazepine anxiolytic lorazepam and the 5-HT2A/2C
      antagonist ritanserin on actual driving performance, objective and subjective
      sleepiness, and nocturnal slow wave sleep. METHODS: Eighteen healthy volunteers
      were treated twice daily for 7 days with ritanserin 5 mg, lorazepam 1.5 mg or
      placebo. Treatments were administered according to a double-blind, cross-over
      design. Tests were performed on day 7 of each treatment week. Sleep EEG was
      recorded during the preceding night. RESULTS: Lorazepam had a pronounced
      impairing effect on lateral position control and induced daytime sleepiness,
      while having no effect on other parameters. In contrast, ritanserin did not
      impair driving performance or affect objectively measured daytime sleepiness,
      while subjects reported to feel more alert during daytime. Moreover, consistent
      with its effects on 5-HT2 receptors, ritanserin increased the amount of nocturnal
      slow wave sleep. There were no relationships between changes in slow wave sleep
      and performance parameters. CONCLUSIONS: Lorazepam administered for 7 consecutive
      days may be hazardous for patients who engage in driving activities. Antagonism
      of 5-HT2A/2C receptors, as accomplished by ritanserin, increases slow wave sleep
      and is devoid of effects on objective sleepiness and driving behaviour. Whether
      this extends to other cognitive and psychomotor domains remains to be
      established.

PMID- 11314682
TI  - Repeated exposure to inhaled toluene induces behavioral and neurochemical cross
      sensitization to cocaine in rats.
AB  - RATIONALE: Toluene is a solvent found in many commercial products and is
      frequently abused by inhalation. Whether previous exposure to toluene alters
      subsequent responses to other drugs of abuse is not known. OBJECTIVES: This study
      determined the effects of repeated toluene exposure on the acute motor-stimulant
      response to cocaine and on cocaine-induced dopamine (DA) concentrations in the
      nucleus accumbens (NAc). METHODS: One week following bilateral cannulae
      implantation over the NAc, 27 adult, male Wistar rats began a daily 30-min
      exposure regimen to either toluene (8,000 ppm) or air for ten sessions.
      Approximately 24 h or 96 h after their last exposure, animals were injected with
      either saline or cocaine (15 mg/kg, i.p.) and locomotor activity and DA
      concentrations in the NAc were measured. RESULTS: Exposure to toluene rendered
      the rats immobile, and the time required for recovery of normal posture decreased
      across the ten sessions. In all animals tested, systemic cocaine administration
      enhanced both locomotor activity and DA concentrations in the NAc. These
      increases, however, were significantly greater in rats previously exposed to
      toluene. CONCLUSIONS: Overall, these findings show that repeated toluene exposure
      enhances behavioral and neurochemical responses to subsequent cocaine
      administration.

PMID- 11314683
TI  - Insulin and leptin levels in patients with schizophrenia or related psychoses--a
      comparison between different antipsychotic agents.
AB  - RATIONALE: Conventional as well as newer antipsychotics cause weight gain, and,
      in the regulation of body weight, both insulin and leptin are hormones involved.
      OBJECTIVE: The aim of the present study was to compare these hormonal levels in
      patients on treatment with different antipsychotics. METHODS: Nineteen patients
      receiving conventional antipsychotics, 14 patients receiving clozapine and 14
      patients receiving olanzapine, were studied. Fasting blood samples for insulin,
      leptin, glucose, and drug serum concentrations were analyzed. In addition, body
      mass index (BMI) was calculated. RESULTS: The median insulin level was
      significantly higher in the patients receiving olanzapine than in those receiving
      conventional agents, whereas there was no significant difference in insulin
      between the clozapine and the other two groups. However, in the clozapine group,
      insulin levels were positively correlated to the drug serum concentration. BMI
      was elevated in about half of the patients, with no difference being found
      between the groups. The leptin level was significantly higher in the women than
      in the men in the conventional agent group, but not in the olanzapine or
      clozapine groups. CONCLUSIONS: The higher insulin level in the patients receiving
      olanzapine than in those receiving conventional antipsychotics, despite similar
      BMI, points to a probable influence of olanzapine on insulin secretion. The
      correlation between the insulin levels and the clozapine concentration indicates,
      in addition, an influence of clozapine on insulin secretion. The gender
      difference in leptin, i.e. females normally having higher leptin levels than
      males, was found in the conventional agent group, but not in the olanzapine or
      clozapine groups, suggesting that also leptin regulation is altered during
      olanzapine or clozapine treatments. Moreover, it was mainly due to an increase of
      leptin in the males that leptin levels were equalized between sexes in the
      olanzapine group. We conclude that the influence of olanzapine and clozapine on
      both insulin and leptin levels might be associated with their weight-gain
      inducing ability, while other mechanisms may be involved in the weight gain
      caused by conventional antipsychotics.

PMID- 11314684
TI  - Chronic unpredictable stress, but not chronic predictable stress, enhances the
      sensitivity to the behavioral effects of cocaine in rats.
AB  - RATIONALE: Chronic unpredictable stress, in which the type and timing of stress
      exposures are varied, alters protein levels in the mesolimbic DA system in a
      manner previously shown to be associated with enhanced behavioral responsiveness
      to cocaine. Chronic exposure to the same or predictable stress (restraint) does
      not. Thus, we examined the effects of chronic unpredictable and chronic
      predictable (restraint) stress on the locomotor activating and place conditioning
      effects to low cocaine doses. OBJECTIVE: To test whether chronic unpredictable
      stress enhances the sensitivity to the behavioral effects of cocaine. METHODS:
      Rats were exposed to 10 days of chronic unpredictable stress, of chronic
      predictable (restraint) stress, or were not stressed. One day following cessation
      of stress exposure, locomotor activity to cocaine (0 or 7.5 mg/kg) was assessed
      for 4 consecutive days and corticosterone levels on the last day were determined.
      In other experiments, the effects of the chronic stress procedures on cocaine
      (0.5 and 7.5 mg/kg) place conditioning using an unbiased procedure were assessed.
      RESULTS: Chronic unpredictable, but not chronic predictable, stress transiently
      increased the locomotor activating effects of cocaine and this was correlated
      positively with corticosterone levels. Chronic unpredictable, but not chronic
      predictable, stress also enhanced the place conditioning effects of cocaine:
      increased place preference was seen with the low dose and a pronounced place
      aversion occurred with the high dose. CONCLUSIONS: These data demonstrate that
      chronic unpredictable stress enhances the behavioral effects of cocaine,
      including its aversive effects, whereas chronic predictable stress (restraint) is
      without effect.

PMID- 11314685
TI  - Managing depression in outpatients.

PMID- 11314686
TI  - Managing depression in outpatients.

PMID- 11314687
TI  - Managing depression in outpatients.

PMID- 11314688
TI  - Managing depression in outpatients.

PMID- 11314689
TI  - Managing depression in outpatients.

PMID- 11314690
TI  - Managing depression in outpatients.

PMID- 11314691
TI  - Managing depression in outpatients.

PMID- 11314692
TI  - Fine particulate air pollution and mortality in 20 U.S. cities.

PMID- 11314693
TI  - Chromosomal abnormalities in chronic lymphocytic leukemia.

PMID- 11314694
TI  - Herbal medications in the Physician's Desk Reference.

PMID- 11314695
TI  - [Benign fibrous histiocytoma of the bone: MR diagnosis].

PMID- 11314696
TI  - [Ovarian hyperstimulation syndrome (OHSS): a radiologically little known
      complication of the hormonal treatment of infertility].

PMID- 11314697
TI  - [Basal meningitis with brain stem infarction in Boeck's disease].

PMID- 11314698
TI  - Isolated angiitis of the CNS in children.
AB  - OBJECTIVE: To clarify the clinical features and pathologic manifestations of
      isolated angiitis of the CNS (IACNS) in children. METHODS: The authors report two
      new cases and summarize the literature of childhood IACNS confirmed by pathology.
      RESULTS: IACNS affecting small vessels (n = 5). Neurologic manifestations
      included headaches, focal seizures, and progressive, behavioral, or multifocal
      neurologic impairment. MRI showed multifocal, T2-hyperintense, cerebral lesions
      without mass effect or tumor-like lesions. CSF, erythrocyte sedimentation rate,
      and cerebral angiograms were often normal.CNS biopsy disclosed a nongranulomatous
      vasculitis. Children were treated with prednisone alone or combined with
      cyclophosphamide. One child died. Four children had a favorable outcome. IACNS
      affecting large and medium arteries (n =5). Three children presented with acute
      ischemic stroke or TIA. Brain CT showed ischemic infarcts. Two children presented
      with subarachnoid hemorrhage. In this group, CSF, erythrocyte sedimentation rate,
      and angiograms were often abnormal. No patient received immunosuppressive
      therapy. Five children died. Autopsy showed granulomatous IACNS (n =5).
      CONCLUSIONS: Clinical and radiologic features correlate with the size of affected
      vessels. Prognosis differs between groups. Potential markers of poor outcome are
      acute stroke presentation secondary to large and medium-sized artery involvement,
      granulomatous angiitis, and delayed institution of immunosuppressive therapy.

PMID- 11314700
TI  - Alternative medicine. A new breed of healers.

PMID- 11314699
TI  - Platelet-derived growth factor/insulin-like growth factor-1 combination and bone
      regeneration around implants placed into extraction sockets: a histometric study
      in dogs.
AB  - This study evaluated, by histometric analysis, the wound healing process of bone
      around implants placed into extraction sockets with or without the concurrent
      application of a combination of platelet-derived growth factor (PDGF) and insulin
      like growth factor (IGF-1). Mandibular premolars were removed, and 32 implants
      were inserted in eight dogs. Before insertion, two implants received a single
      application of 5 micrograms/mL of PDGF and IGF-1 delivered in 0.10 mL of 4%
      methylcellulose gel or 0.10 mL of 4% methylcellulose gel only as a control. To
      label regenerated bone, a 2% calcein green solution was administered by
      intramuscular injection at 0, 7, 15, 30, 45, 60, and 75 days after implant
      insertion. Three, 8, and 12 weeks after implant insertion, undecalcified sections
      were obtained, and the degree of bone contact with the implant surface, the bone
      area, and the intensity of bone labeling were measured into the limits of the
      threads of the implant. Greater extension of bone/implant contact (paired t test,
      P < .05) was observed in test (22.4% +/- 13.7%) than in control (17.2% +/- 13.6%)
      implants at 3 weeks. One-way ANOVA revealed a higher intensity of bone labeling
      (P < .05) at 3 weeks than at 12 weeks (127.8 +/- 42.59 and 56.7 +/- 26.34, gray
      scale values) for test implants. Within the limits of the present study, it was
      concluded that the combination of PDGF/IGF-I actively took part in the initial
      phase of bone repair.

PMID- 11314701
TI  - Primary care of patients without insurance by community health centers.
AB  - Community health centers (CHCs) are in a strong position to meaningfully
      contribute to health promotion, early detection, and improvement in health care
      outcomes for some of the most vulnerable person in the nation, since almost one
      in three users of federally funded CHCs was uninsured in 1994. The purpose of
      this article is to compare uninsured CHC users with uninsured people nationwide.
      Data for the analysis came primarily from two population-based surveys: the 1994
      National Health Interview Survey (NHIS) and the 1995 Community Health Center
      (CHC) User Survey.

PMID- 11314702
TI  - Prognostic value of electromyography in acute peripheral facial nerve palsy.
AB  - OBJECTIVE: To analyze the value of electromyography in predicting recovery from
      acute idiopathic facial nerve paralysis. STUDY DESIGN: Retrospective case-series
      review. SETTING: University-based hospital department of otorhinolaryngology/head
      neck surgery. PATIENTS: Three hundred fifty-five patients with sudden facial
      paralysis of unknown cause (Bell's palsy). INTERVENTION: Treatment consisted
      uniformly of high-dose prednisolone, dextran, and pentoxifylline. Prognostication
      was based on electromyography performed not earlier than 10 to 14 days after the
      onset of palsy. The findings were classified according to Seddon into neurapraxia
      and axonotmesis/ neurotmesis. There is an inherent statement on prognosis in this
      classification because neurapraxia is presumed to recover completely within 8 to
      12 weeks, whereas axonotmesis is most likely to be followed by sequelae. MAIN
      OUTCOME MEASURES: Facial nerve function after 6 months. RESULTS: Complete
      recovery was predicted correctly in 92.4% of cases. For the relatively rare and
      therefore principally more difficult predictable event defective recovery
      prognosis was still accurate in 80.8%. CONCLUSION: The detection of spontaneous
      fibrillation in needle electromyography is a reliable sign predicting unfavorable
      outcome. An accuracy of 80.8% for predicting unfavorable outcome may be
      sufficient to advise patients what to expect in the course of their facial nerve
      disorder. However, it seems dubious to build a decision about surgical
      intervention on such a test, because in the process, unnecessary surgery would be
      accepted for as much as one fifth of the patient population.

PMID- 11314703
TI  - Antonio Scarpa and the discovery of the membranous inner ear.
AB  - OBJECTIVE: To give a historical perspective of Antonio Scarpa's contributions to
      otology, specifically the discovery of the inner ear organs as the foundation for
      the experimental work that followed. BACKGROUND/METHOD: Scarpa's original
      descriptions of the human inner ear were translated from the Latin text, and his
      illustrations were analyzed and compared with current knowledge. CONCLUSIONS:
      Antonio Scarpa's anatomic and clinical studies place him among the great
      scientists of the eighteenth century. His discoveries about the inner ear
      established the limit of what could be learned without advanced histologic
      techniques and provided the foundation for the work that eventually led to the
      modern understanding of ear physiology.

PMID- 11314704
TI  - Goblet cell density in acute otitis media caused by Moraxella catarrhalis.
AB  - HYPOTHESIS AND BACKGROUND: Secretory otitis media is associated with a highly
      increased goblet cell density, confirming the secretory pathogenesis of this
      disease. Previous studies have shown that the middle ear goblet cell density, and
      thus the secretory capacity, are massively increased during experimental acute
      otitis media and at least 6 months thereafter, conceivably predisposing to the
      subsequent development of secretory otitis media. These studies used middle ear
      inoculation of either Streptococcus pneumoniae, nontypeable Haemophilus
      influenzae, or H. influenzae type b. The present study aimed at determining the
      goblet cell density during and after acute otitis media caused by Moraxella
      catarrhalis to clarify whether this bacterium induces an equivalently enhanced
      secretory capacity. METHODS: Twenty-five 25 rat middle ears were inoculated with
      M. catarrhalis. Five rats were killed on days 4, 8, 16, 60, and 180 after
      inoculation, followed by staining, dissection, and whole-mount embedding of the
      middle ear mucosae. The goblet cell density was determined by counting in 24
      fields, covering the entire middle ear. RESULTS: In comparison with 25 normal
      middle ears, the goblet cell density was significantly increased in almost all
      counting localities, from day 4 and < or = 2 months after inoculation. The goblet
      cell density peaked on day 16, subsided thereafter, and in some areas reached a
      normal level 6 months after the acute incident. Mucosal areas containing goblet
      cells were consistently enlarged, thus leaving the middle ear with an increased
      secretory capacity during and 6 months after inoculation. CONCLUSION: The goblet
      cell density of the middle ear mucosa is increased during acute otitis media
      caused by M. catarrhalis and up to several months thereafter. This may predispose
      to the subsequent development of secretory otitis media. However, in comparison
      with acute otitis media caused by other bacteria, M. catarrhalis induced only
      modest changes in goblet cell density.

PMID- 11314705
TI  - Harold Schuknecht and pathology of the ear.
AB  - BACKGROUND: Like Joseph Toynbee and Karl Wittmaack before him, Harold Schuknecht
      understood that studying pathology was the key to advancing the scientific basis
      of neurotology. His work elucidated the pathophysiology of the most common
      neurotologic disorders, including benign paroxysmal positional vertigo, Meniere's
      disease, and viral neurolabyrinthitis. Schuknecht was a tireless crusader against
      medical and surgical treatments that he considered to have little scientific
      foundation. His textbook Pathology of the Ear remains the definitive work in the
      field.

PMID- 11314706
TI  - Bilateral paragangliomas with associated venous anomalies.

PMID- 11314707
TI  - Radiation-induced malignant tumors after stereotactic radiosurgery.

PMID- 11314708
TI  - Cochlear nerve aplasia and cochlear implantation: author's reply.

PMID- 11314709
TI  - Invasiveness of fibroblasts from experimental cholesteatomas.
AB  - HYPOTHESIS: Cultured fibroblasts derived from experimental gerbil cholesteatoma
      tissue exhibit an invasive phenotype in comparison with normal fibroblasts.
      BACKGROUND: Aural cholesteatomas are enlarging accumulations of keratin debris
      caused by keratinizing squamous epithelium in the middle ear. They
      characteristically result in the destruction of adjacent tissues, specifically
      bone erosion. The mechanisms by which cholesteatomas relentlessly invade the
      structures of the temporal bone are varied, but it has been suggested that one
      factor contributing to the aggressive nature of cholesteatomas is the
      transformation of resident fibroblasts into an invasive phenotype. METHODS: The
      ability of cultured normal and cholesteatoma fibroblasts to invade a basement
      membrane matrix in a Boyden chamber assay was examined. RESULTS: Less than 1% of
      gerbil fibroblasts invaded the matrix, compared with almost 10% of the invasive
      HT-1080 fibrosarcoma cells. Normal and cholesteatoma fibroblasts did not differ
      from each other in their invasive potential. CONCLUSION: Normal fibroblasts and
      fibroblasts from induced cholesteatomas do not exhibit the invasive phenotype
      characteristic of true neoplastic cells.

PMID- 11314710
TI  - Intratympanic dexamethasone for sudden sensorineural hearing loss: clinical and
      laboratory evaluation.
AB  - OBJECTIVE: To discuss the value of intratympanic dexamethasone (IT-DEX) perfusion
      for sudden sensorineural hearing loss (SSNHL), clinically and in an animal model.
      STUDY DESIGN: Retrospective case review of 10 patients with SSNHL treated with IT
      DEX. The findings are correlated with this institution's previous findings from a
      study of IT-DEX in guinea pigs. SETTING: Ambulatory tertiary otologic referral
      center. PATIENTS: Sequential patients with SSNHL who chose IT-DEX treatment.
      INTERVENTIONS: Dexamethasone 0.5 mg was injected transtympanically and bathed the
      round window for 20 minutes. Animal study: 79 ears were randomized into five
      groups: control, IT-DEX versus intravenous (IV)-DEX, IT-DEX with histamine, IT
      DEX with hyaluronic acid, and IT-DEX with dimethylsulfoxide. MAIN OUTCOME
      MEASURES: Clinical study: postprocedure audiometry. Animal study: perilymph
      steroid concentration. RESULTS: IT-DEX results in significant hearing improvement
      and in significantly higher perilymph concentration of steroid than IV-DEX.
      CONCLUSIONS: IT-DEX is an appropriate treatment option for the treatment of
      SSNHL. Further study of dosages and frequency of administration is warranted.

PMID- 11314711
TI  - The nucleus double array cochlear implant: a new concept for the obliterated
      cochlea.
AB  - OBJECTIVE: To increase the number of intracochlear electrodes that may be
      inserted into a totally obliterated cochlea, a special implant has been developed
      in collaboration with Cochlear Limited. This implant features two separate
      electrode carriers containing 11 and 10 active electrodes, respectively, as well
      as a reference electrode located on the receiver-stimulator package. The
      potential stimulation modes available with this device therefore include
      monopolar and bipolar stimulation, and stimulation between both arrays. SURGICAL
      TECHNIQUE: A cochleostomy anterior to the round window provides access to the
      basal turn (both the scala tympani and the scala vestibuli), and new built
      connective tissue and bone can be removed until the anterior wall of the basal
      turn is approached. A second cochleostomy is performed at the second turn caudal
      of the cochleariform process and 2 mm anterior of the oval window after removal
      of the incus. New tissue should also be removed if necessary. The two electrode
      carriers are then placed into the scala tympani of the basal and the scala
      vestibuli of the second turn, respectively. The remaining surgical procedure is
      identical with that used for cochlear implantation in patients without
      obliterated cochleas. PATIENTS: In this clinical study, 10 patients aged 32 to 66
      years with an obliterated cochlea each received a double array cochlear implant.
      All patients had total obliteration of the basal turn either on preoperative
      imaging or during surgery. Intraoperatively, the second turn was not obliterated
      in only 4 of 10 patients. Postoperatively, a standard audiologic test battery was
      used to determine auditory improvement over time. POSTOPERATIVE RESULTS: All
      patients achieved significantly improved speech understanding when the additional
      apical electrode array was used, compared with the use of each electrode array
      independently. No complications occurred. CONCLUSION: In patients with a totally
      obliterated cochlea, the number of intracochlear electrodes can be increased by
      use of the Nucleus double array implant. As a result, patients achieve
      significantly better auditory results.

PMID- 11314712
TI  - Chronic myringitis: prevalence, presentation, and natural history.
AB  - OBJECTIVE: The aim of this study was to examine the clinical presentation and
      natural history of chronic myringitis (CM). STUDY DESIGN: Retrospective case
      review. SETTING: Tertiary referral center. PATIENTS: Chronic myringitis is
      defined as a loss of tympanic membrane epithelium for >1 month without disease
      within the tympanic cavity. Seven hundred fifty patient records were reviewed to
      determine the prevalence of CM in an academic otology practice. The records of 40
      patients (45 ears) with CM seen between 1995 and 1999 inclusive were reviewed.
      MAIN OUTCOME MEASURES: The series was reviewed with attention to previous medical
      and otologic history, the nature and duration of symptoms, the physical findings,
      and management. RESULTS: The prevalence of CM was found to be -1% (approximately
      one fourth as common as cholesteatoma). Symptoms were often present for many
      years before the diagnosis of CM, with CM often mistaken for chronic otitis
      media. Sixty percent of patients had undergone previous otologic procedures.
      There did not appear to be an association between CM and systemic disease.
      Physical findings were varied, with granulation tissue and tympanic membrane
      perforations often occurring transiently. The clinical course of CM is typified
      by recurrent episodes of symptoms, often interspersed with long asymptomatic
      periods. A subset of CM can result in an acquired atresia. The most effective
      treatment appeared to be prolonged topical medications, surgery being reserved
      for only the most refractory cases. CONCLUSIONS: Chronic myringitis is often
      mistaken for chronic otitis media. Such confusion prolongs the initiation of
      appropriate management and sometimes leads to needless tympanomastoid surgery.
      The otologist should be aware of this clinical entity and its varied
      presentation.

PMID- 11314713
TI  - The contour electrode array: safety study and initial patient trials of a new
      perimodiolar design.
AB  - OBJECTIVE: The aim of these studies was to investigate the insertion properties
      and safety of a new intracochlear perimodiolar electrode array design (Contour).
      BACKGROUND: An electrode array positioned close to the neural elements could be
      expected to reduce stimulation thresholds and might potentially reduce channel
      interaction. METHODS: Two sequential studies were conducted. In study 1, the
      Contour electrode array was inserted in 12 human temporal bones. After cochlear
      surface preparation, the position of the array was noted and the basilar membrane
      was examined for insertion damage. On the basis of the outcome of this temporal
      bone study, study 2 investigated the Contour array, mounted on a Nucleus CI-24 M
      device and implanted in three adult patients. RESULTS: Study I showed that in 10
      temporal bones, the Contour array was positioned close to the modiolus, and the
      basilar membrane was intact. In the two remaining bones, the arrays had pierced
      the basilar membrane and were positioned in the scala vestibuli apical to the
      penetration. Statistical analysis showed an equivalent probability of insertion
      induced damage of the two array designs. In study 2, image analysis indicated
      that the Contour electrodes were positioned closer to the modiolus than the
      standard Nucleus straight array. Lower T and C levels, but higher impedance
      values, were recorded from electrodes close to the modiolus. Initial speech
      perception data showed that all patients gained useful open-set speech
      perception, two patients achieving scores of 100% on sentence material 3 months
      postoperatively. CONCLUSIONS: The temporal bone studies showed the Contour
      electrode array to be generally positioned closer to the modiolus than the
      standard Nucleus straight array, and to have an equivalent probability of causing
      insertion-induced damage.

PMID- 11314714
TI  - The influence of age at implantation on performance with a cochlear implant in
      children.
AB  - OBJECTIVE: This study involved the assessment of speech recognition abilities as
      a function of age at implantation and length of cochlear implant use in children
      who received the Nucleus CI22M cochlear implant. STUDY DESIGN: Two separate
      analyses were performed. The first analysis involved the assessment of speech
      recognition performance as a function of length of time with a cochlear implant
      in 48 patients evaluated at 7 years of age. The second analysis involved the
      assessment of speech recognition performance as a function of age at implantation
      in 53 patients evaluated 36 months after implantation. Patients were divided into
      four groups based on length of implant use or age at implantation, and the
      results were analyzed by a repeated-measures analysis of variance. SETTING: This
      study was carried out at a tertiary academic medical center. PATIENTS: Patients
      consisted of children implanted with a Nucleus Multi Channel cochlear implant
      programmed with the SPEAK encoding strategy. Their ages at the time of evaluation
      ranged from 5.5 to 7.8 years. Their ages at implantation ranged from 2.4 to 14.5
      years. INTERVENTIONS: All patients received a Nucleus Multi Channel cochlear
      implant programmed with the SPEAK encoding strategy. Word and sentence
      recognition tests were administered at various ages and at several
      postimplantation intervals. MAIN OUTCOME MEASURES: Performance as a function of
      length of cochlear implant use and as a function of age at implantation. RESULTS:
      Patients performed significantly better as length of cochlear implant use
      increased and age at implantation decreased. When patients were tested at a fixed
      postimplantation time interval (36 months), there was an overall trend for
      patients who received the implant at a younger age to perform better in spite of
      being younger at the time of evaluation. However, these effects were not
      statistically significant for all speech recognition tests that were
      administered. CONCLUSIONS: These results confirm previous findings indicating
      continued improvement of speech recognition with time in implanted children.
      Furthermore, the results support the concept of the advantage of a younger age at
      implantation.

PMID- 11314715
TI  - Use of the telephone in prelingually deaf children with a multichannel cochlear
      implant.
AB  - OBJECTIVE: To assess progress in the use of the telephone in a group of
      prelingually deaf children after cochlear implantation. SETTING: Tertiary
      referral pediatric cochlear implant center in the U. K. STUDY DESIGN: A
      prospective study was undertaken on a consecutive group of 150 congenital and
      prelingually deaf children up to 5 years after implantation. The study group was
      confined to prelingually deaf children aged less than 7 years at the time of
      implantation. No child was lost to follow-up, and there were no exclusions from
      the study. At the time of the study, 129 children had reached the 1-year stage,
      and 91, 68, 40, and 23 had reached the 2-, 3-, 4-, and 5-year intervals,
      respectively. METHODS: A specifically designed profile was used to assess the
      telephone use of the implanted children. Regression analysis was used to assess
      the correlation between the results of the telephone profile with the outcomes of
      the Iowa sentence test and connected discourse tracking. RESULTS: After
      implantation, prelingually deaf children showed significant progress in telephone
      use over time, not reaching a plateau at the 5-year interval (median score 27
      with maximum score available 34). The results of the telephone profile showed
      significant correlations with the other tests of speech perception (correlation
      coefficients from 0.47 to 0.79, all statistically significant p < 0.0001).
      CONCLUSION: The telephone profile provided a useful method of monitoring
      children's telephone use. The profile was easily administered, and it was
      sensitive in assessing the progress of prelingually deaf children with cochlear
      implants. Outcomes from the profile were highly correlated with results from
      other widely used closed- and open-set tests.

PMID- 11314717
TI  - Temporal bone pathology in Cornelia de Lange syndrome.
AB  - OBJECTIVE: This study aimed to demonstrate the temporal bone histopathology of
      Cornelia de Lange syndrome. STUDY DESIGN: Histopathologic examination of an
      infant with this syndrome. SETTING: This study was performed at the temporal bone
      laboratory. Fukushima Medical University, Fukushima. RESULTS: The authors
      describe interesting temporal bone findings of this syndrome: anomalies of the
      middle and inner ear and the facial nerves. CONCLUSIONS: This is the second case
      report describing the histologic findings of the temporal bone in Cornelia de
      Lange syndrome in the English literature.

PMID- 11314716
TI  - Multichannel cochlear implantation in visually impaired patients.
AB  - OBJECTIVE: To evaluate the outcome of cochlear implantation in patients with
      severe to profound hearing loss and visual impairment. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral center with a large
      cochlear implant program. PATIENTS: Six adults and two children with severe or
      profound hearing loss and significant visual impairment underwent multichannel
      cochlear implantation. Follow-up period ranged from 6 months to 9 years. Case
      history, etiology of visual and hearing loss, and benefit from cochlear implant
      were evaluated. INTERVENTIONS: Cochlear implantation and subsequent
      rehabilitation. MAIN OUTCOME MEASURES: Speech perception measures were selected
      based on the patient age and cognitive abilities. Identical measures were used in
      each patient before and after implantation. RESULTS: As a group, patients did
      well after cochlear implantation. There was significant improvement in speech
      perception when compared with the score before implantation. CONCLUSIONS:
      Cochlear implants can play a significant rehabilitative role in patients with
      severe visual and auditory impairment. Additional skills are required by the
      implant team for rehabilitation of patients with multiple sensory deficits.

PMID- 11314718
TI  - Tullio phenomenon with dehiscence of the superior semicircular canal.
AB  - HYPOTHESIS: The goal of the investigation was to determine if vector analysis of
      nystagmus in a patient with the Tullio phenomenon could determine the source of
      the nystagmus. BACKGROUND: The Tullio phenomenon consists of the combination of
      vertigo and abnormal eye and/or head movements provoked by sound. Dehiscence of
      the superior semicircular canal can be found in certain patients with the Tullio
      phenomenon. METHODS: The patient was tested with pure tones ranging from 250 to
      3,000 Hz at 95dB HL. The time course of the three-dimensional vector of eye
      movement, including torsion and vertical and horizontal displacement angles was
      determined by individual stop-frame analysis of digitized video. RESULTS: Torsion
      amplitude varied from 1 to 7 degrees; vertical amplitude varied from 1 to 5
      degrees; and horizontal amplitude varied less than 1.5 degrees. The maximal
      response occurred on stimulation of the right ear with a 1,250-Hz 95-dB HL tone.
      This elicited a reliable counterclockwise torsional and down-beating fast phase
      nystagmus as seen from the examiner's point of view. Comparison of the nystagmus
      with known canal vectors identified the right superior semicircular canal as the
      source of stimulation. High-resolution computed tomography scan of the temporal
      bone showed a definite right superior canal dehiscence. CONCLUSION: The origin of
      nystagmus from the Tullio phenomenon can be identified by calculating the three
      dimensional vector of the observed nystagmus. We show that vector analysis of the
      observed eye movement can be used to infer the source of nystagmus in these
      patients. The development of real-time, three-dimensional vector analysis of
      nystagmus is desirable.

PMID- 11314719
TI  - A liberatory maneuver for the treatment of horizontal canal paroxysmal positional
      vertigo.
AB  - OBJECTIVE: The purpose of this study was to determine the effectiveness of a new
      liberatory maneuver in the management of the geotropic variant of horizontal
      canal paroxysmal positional vertigo (HC-PPV). STUDY DESIGN: Case review. SETTING:
      Outpatient clinic. PATIENTS: The diagnosis of HC-PPV was based on the history of
      recurrent sudden crisis of vertigo associated with bursts of horizontal geotropic
      paroxysmal nystagmus provoked by turning the head from the supine to either
      lateral position. The patients were 11 men and 21 women ranging in age from 30 to
      85 years (average 55.43 years), and the average duration of symptoms was 7.68
      days. INTERVENTIONS: All patients were treated with a liberatory maneuver based
      on the hypothesis that the syndrome is caused by the presence of free-floating
      dense particles inside the endolymph of the posterior arm of the semicircular
      horizontal canal. The maneuver favors their outmigration into the utricle.
      Patients were reexamined immediately after the treatment and again 2 days later.
      MAIN OUTCOME MEASURE: The treatment outcome was considered as responsive when,
      after one or more liberatory maneuvers, the clinical signs of PPV disappeared at
      the end of physical therapy. RESULTS: The liberatory maneuver resulted in a
      complete remission of the positioning vertigo and nystagmus in all patients after
      the first session. CONCLUSIONS: This approach represents a simple and effective
      approach to the management of the geotropic form of HC-PPV.

PMID- 11314720
TI  - Objective method for differentiating between drug-induced vestibulotoxicity and
      cochleotoxicity.
AB  - HYPOTHESIS: An objective direct method is proposed to differentiate between drug
      induced functional vestibulotoxicity and cochleotoxicity. BACKGROUND: Many
      substances are ototoxic. Although there are objective methods to directly
      evaluate functional cochlear toxicity (auditory nerve brainstem responses [ABR]),
      it is more difficult to assess direct functional ototoxicity to the various
      vestibular end organs. METHODS: Short-latency vestibular evoked potentials (VsEP)
      from different vestibular end organs and ABR, were used to assess functional
      impairment of the vestibular and cochlear end organs caused by daily injections
      of the aminoglycoside amikacin (known to be preferentially cochleotoxic) in
      guinea pigs. RESULTS: There was no significant change in the various VsEPs.
      whereas ABR thresholds were elevated, confirming the selective functional
      cochleotoxicity previously reported, as evaluated by other (mainly nondirect)
      methods. CONCLUSION: This study demonstrates the feasibility in general of using
      short-latency evoked potentials to evaluate functional cochleotoxicity and
      vestibulotoxicity of ototoxic drugs and to differentiate between them.

PMID- 11314721
TI  - Mature teratoma of the middle ear.
AB  - OBJECTIVE: The authors report a case of mature teratoma of the middle ear in a 3
      year-old girl with a 1-year history of otitis media. METHODS AND RESULTS:
      Radiologic investigation revealed a partially cystic lesion of the petrous
      portion of the right temporal bone. It produced opacification of the middle ear
      as well as destruction of septal air cells. The patient underwent a subtotal
      petrosectomy. Histologically, the tumor was composed of an intimate admixture of
      mature tissues representing all three germ layers, including brain, myelinated
      nerve trunks, skeletal muscle, bone, immature cartilage, seromucinous glands, and
      respiratory epithelium. Of note within the brain tissue was choroid plexus within
      an ependyma-lined rudimentary ventricle. Immunohistochemical studies were also
      performed. Twenty months after surgery, the patient was well, with complete
      recovery from symptoms. CONCLUSION: Teratomas of the middle ear are rare
      neoplasms. Only a few examples have been reported. As a rule, they are cured by
      resection and do not require adjuvant therapy.

PMID- 11314722
TI  - Vestibular schwannomas: correlations between magnetic resonance imaging and
      histopathologic appearance.
AB  - BACKGROUND: The indication for surgery of vestibular schwannomas (VS) remains
      controversial and depends on several factors. The ability to predict their
      patterns of growth would allow better surgical planning. This growth may depend
      on tumoral proliferation but also depends on dystrophic changes. OBJECTIVE: The
      aim of this study was to evaluate the role of magnetic resonance imaging (MRI) in
      predicting the evolution of VS. For this purpose, the authors attempted (1) to
      compare the MRI appearance of VS with its histopathologic features, (2) to
      correlate the MRI appearance of VS and its histopathologic features with its
      size, and (3) to evaluate the index of proliferation (IP) of each VS. PATIENTS
      AND METHODS: Thirty VS were studied with MRI before surgery. The VS were measured
      and classified as homogeneous, heterogeneous, and cystic. After surgery, IP was
      evaluated with immunohistochemical study using MIB-1 monoclonal antibody, and
      compared with tumor size. Pathologic studies evaluated the prevalence of Antoni
      type A and type B tissue, the amount of fibrosis, and the presence of siderin
      loaded macrophages, xanthomatous cells, and cysts. RESULTS: The IP was low (0.2%
      2.2%) and was not correlated with VS size. On MRI, 13 VS were homogeneous, 12
      heterogeneous, and 5 cystic. The 13 homogeneous VS were smaller and were
      predominantly made of Antoni type A tissue. The 12 heterogeneous and 5 cystic VS
      were larger and were predominantly made of Antoni type B/mixed tissue.
      Heterogeneous and cystic VS showed significantly more hemosiderin deposits. There
      was a significant relation between the amount of hemosiderin deposits and the
      mean size of VS. Microscopic cysts were observed only in VS with cystic MRI
      appearance. Fibrosis was present in all tumors regardless of their size and MRI
      appearance. CONCLUSION: A heterogeneous MRI aspect (correlated with larger mean
      size) not only is related to the ratio of type A to type B tissue but also is
      caused by other pathologic changes, mainly hemosiderin deposits and cystic
      formation. Increasing tumor size probably depends less on IP than on dystrophic
      changes (hemosiderin, cysts) and/or on the presence of type B tissue.

PMID- 11314723
TI  - Prognostic value of magnetic resonance imaging findings in hearing preservation
      surgery for vestibular schwannoma.
AB  - OBJECTIVE: The purpose of this study was to determine whether three magnetic
      resonance imaging (MRI) findings (tumor size, extension to the fundus,
      intralabyrinthine signal intensity) have a predictive value to hearing
      preservation in vestibular schwannoma surgery. STUDY DESIGN: A retrospective
      study was conducted of preoperative high-resolution MR images in a series of
      consecutive hearing preservation attempts for vestibular schwannomas. PATIENTS:
      Twenty-six consecutive records of patients with an acoustic tumor removed via a
      retrosigmoid transcanal approach were analyzed, and the MR images were reviewed
      blindly and compared with postoperative hearing. SETTING: The study took place in
      a tertiary referral center. Imaging Techniques: The MR sequences used in this
      study were unenhanced and gadolinium-enhanced T1-weighted spin-echo images and
      gradient echo images (3DFT-CISS). MAIN OUTCOME MEASURES: The predictive value of
      three MRI signs was analyzed: tumor size, lateral extension of the tumor (with
      and without obliteration of the fundus), and the maintenance of, or decrease in,
      the intralabyrinthine signal intensity on the affected side in comparison with
      the signal intensity on the opposite normal side as seen on 3DFT-CISS images.
      RESULTS: The tumor size in ears in which hearing was preserved averaged 15 mm and
      was 17 mm in those cases where hearing was not preserved. Hearing was preserved
      in 50% of ears when the tumor did not extend to the fundus but in only 33% when
      the fundus was obliterated by tumor. A "normal" intralabyrinthine signal on CISS
      images (being an isointense signal when compared with the contralateral
      unaffected ear) was followed by hearing preservation in 82% of ears, whereas in
      cases where the intralabyrinthine signal was low, hearing was preserved in only
      20%. This correlation was statistically significant (p < 0.05). CONCLUSION: The
      intralabyrinthine signal intensity on 3DFT-CISS gradient-echo images is a
      valuable additional tool for determining candidacy for hearing preservation
      surgery. In two cases with preoperative decrease in signal intensity of the
      intralabyrinthine fluids, control MRI after surgery showed spontaneous recovery
      of normal intralabyrinthine signal intensity. The authors hypothesize that
      vascular compression in the internal auditory canal by the tumor is responsible
      for the observed intralabyrinthine signal decrease.

PMID- 11314724
TI  - Brainstem response in cerebellopontine angle tumors.
AB  - OBJECTIVE: To evaluate the auditory brainstem response (ABR) findings in
      cerebellopontine angle (CPA) tumors and focus on those with normal ABR results.
      STUDY DESIGN: This was a retrospective evaluation of ABR findings. All subjects
      with diagnosed CPA tumors who were referred for treatment were included.
      PATIENTS: All 309 patients with radiographically confirmed (computed tomography
      or magnetic resonance imaging [MRI]) CPA tumors (153 before 1993 and 156 after
      1993). INTERVENTION: All patients underwent complete audiologic examination,
      electronystagmography, ABR testing, and ipsilateral transtympanic
      electrocochleography. All tumors were histologically confirmed. MAIN OUTCOME
      MEASURES: The patients were categorized according to ABR results (normal or
      pathologic findings or no response); according to histology (vestibular
      schwannomas or meningiomas); and according to tumor size by MRI (small, up to 15
      mm; medium, 16-25 mm; large, 26-40 mm; and very large, over 40 mm). RESULTS:
      Normal ABR results were found in 18.4%; pathologic ABR results in 31.4%; and no
      response in 50.2%. Small vestibular schwannomas (under 15 mm) showed a higher
      incidence of normal ABR results (41.7%). CPA tumors with normal ABR results (n =
      57) caused no hearing loss (n = 12), symmetrical hearing loss (n = 11), or
      ipsilateral hearing loss with Short Increment Sensitivity Index 100% and normal
      acoustic reflex (cochlear deafness, n = 34). Caloric response was normal in 59.7%
      of these tumors. CONCLUSION: Because validation of ABR as screening for acoustic
      tumors is based on diagnosed tumors, and because MRI allows detection of very
      small tumors, the incidence of normal ABR increases and its sensitivity would be
      expected to decrease. ABR is not sufficient for early detection of small CPA
      tumors.

PMID- 11314725
TI  - Introduction: dilemmas in intergenerational versus intragenerational equity and
      risk policy.

PMID- 11314726
TI  - Intergenerational issues regarding nuclear power, nuclear waste, and nuclear
      weapons.
AB  - Nuclear power, nuclear waste, and nuclear weapons raise substantial public
      concern in many countries. While new support for nuclear power can be found in
      arguments concerning greenhouse gases and global warming, the long-term existence
      of radioactive waste has led to requirements for 10,000-year isolation. Some of
      the support for such requirements is based on intergenerational equity arguments.
      This, however, places a very high value on lives far in the future. An
      alternative is to use discounting, as is applied to other resource applications.
      Nuclear weapons, even though being dismantled by the major nations, are growing
      in number due to the increase in the number of countries possessing these weapons
      of mass destruction. This is an unfortunate legacy for future generations.

PMID- 11314727
TI  - Duties to future generations, proxy consent, intra- and intergenerational equity:
      the case of nuclear waste.
AB  - How does one deal with problems of risk transfer if it is the case that
      increasing risks to future generations decreases the risks to present
      generations, and increasing the risks to present generations decreases the risks
      to future generations? In the case of high-level nuclear waste and spent fuel,
      for example, should billions of dollars be spent to secure the wastes and protect
      future generations, or should the same monies be spent on present-day needs,
      under the assumption that future generations will be better able to deal with the
      waste than we are at present? Although these questions may appear insoluble, they
      become less so when one recognizes several common ethical and logical errors that
      beset many discussions of technological risk and duties to future generations.
      After briefly explaining the grounds for inter- and intragenerational equity,
      this analysis argues for three propositions about many treatments of inter- and
      intragenerational ethics: (1) these discussions often err because they frame
      policy arguments in terms that ignore rights and focus on maximizing welfare or
      utility, (2) they err because they frequently frame policy arguments in ways that
      set inter- and intragenerational welfare at odds, when they are not, because they
      ignore ameliorating practices and the conditions for proxy consent, and (3) they
      also err because they engage in risk practices that do not match their risk
      rhetoric.

PMID- 11314728
TI  - Discounting across generations: necessary, not suspect.
AB  - Periodically, ethical objections are raised against the practice of discounting
      for future effects. Concerns about the potential effects on future generations
      from long-term nuclear waste disposal and global climate change have caused these
      ethical objections to recur. This article rebuts the various ethical objections
      to future discounting on practical, ethical, and analytic grounds. Discounting
      for future effects is a ubiquitous practice that cannot be practically prevented.
      In the event that public policy would dictate against future discounting in
      public decisions, such a constraint could never be successfully imposed on
      markets. Market values will always reflect the full, discounted streams of future
      effects even if governments prohibited the practice among individuals. Ethically,
      there is no basis for choosing an upper-bound time horizon beyond which
      discounting should be rejected. Any proposed horizon is arbitrary and has no
      obvious foundation. All decisions are fundamentally irreversible, so opponents of
      future discounting also must define a degree of irreversibility beyond which
      normal discounting should not apply, and defend on ethical grounds the basis for
      this demarcation. This task is further complicated by the likelihood that choices
      are rarely, if ever, as irreversible as opponents suggest. Typical examples given
      to prove future discounting is inappropriate overstate the degree of
      irreversibility actually present and understate subsequent opportunities for
      modifications. Finally, opposition to distant-future discounting on the ground
      that burdens are shifted to future generations must face the fact that such
      shifts are characteristic of intergenerational transfers now practiced widely and
      with great public support.

PMID- 11314729
TI  - The ultimate uncertainty--intergenerational planning.
AB  - The philosophic and practical aspects of intergenerational planning for a 50-100
      year time frame are reviewed, with recognition of its speculative quality.
      Society's near term choice of future physical pathways based on comparative
      quantitative benefit/cost/risk analyses of alternatives is usually modified by
      the intervention of a variety of time-dependent, nontechnical value systems.
      Further, the continuous competition among society's disparate technical systems,
      capital investment choices, and planning objectives all contribute to the
      uncertainty of the intergenerational outcome of any plan. Nevertheless, the
      quantitative planning process provides an essential base. Benefit/cost/risk
      projections are discussed for both the case with a historical database and the
      case without such a historical base. The end-objectives and continuous nature of
      such benefit/cost/risk analyses are described.

PMID- 11314730
TI  - Neighbors in time: development and use of some values for intergenerational
      justice from the Jewish and Christian religious traditions.
AB  - The overlapping understandings of Jewish and Christian traditions (the
      Traditions), both influencing and reincorporating Western culture from the Greeks
      to the present, underpin many of the ethical constructs of present society, in
      ways both obvious and subtle. The concept of justice is central to the ethical
      outlooks of both religious traditions. This article systematically develops
      values related to justice from within the Traditions and extends them to the
      question of intergenerational equity as proposed precepts for assessment and
      action. Many of the results seem familiar because they are deeply embedded in our
      culture. They are assertions that transcend time-the value of human life; an
      obligation to support the necessary interests of others, especially the
      powerless; the concepts of brotherhood, the common good, and stewardship of
      resources; and the transmission of knowledge, resources, and values through the
      vehicles of families and communities. Other ideas from within the Traditions,
      such as giving beyond the requirements of equity and the connection of human life
      with God whose abilities are unbounded by time, continue to draw people beyond
      the limits of culture. These outlooks are organized into 17 statements or
      proposals constitutive of this view of justice. These summary statements are used
      as the basis for comparing a system of principles proposed by a panel of the
      National Academy of Public Administration for intergenerational decision making
      with the views represented by the Traditions. This broaches a broader question of
      fairness in resource distribution. The article concludes with reference to some
      developed resources of the Traditions from which further insight can be drawn,
      and another illustration related to resource allocation. It is hoped that the
      article helps stimulate wider analysis of the values on which our decisions are
      made.

PMID- 11314731
TI  - Municipal waste management: inequities and the role of deliberation.
AB  - Like radioactive waste, municipal solid waste (MSW) requires consideration of a
      complex mix of intergenerational and intragenerational risks surrounded by
      uncertain science. Unlike radioactive waste, MSW is a common problem and hence
      one often perceived to be controllable, at least until a required facility is
      proposed in a particular community. The intragenerational risks focused on local
      communities rouse intense public pressures for management. Although some of the
      risks can be quantified, the risk assessment process cannot deal with all
      questions. This article examines the multiple dimensions of the decisions
      required to be made and the weaknesses of a number of decision tools
      traditionally used. A case is made for the need to integrate decision tools
      appropriate to the risks into reflexive and iterative decision processes open to
      public involvement. It is argued that this presents the best hope of both
      optimizing decisions about the intragenerational risks as well as raising public
      debate about the importance of sustainable waste management in transgenerational
      terms.

PMID- 11314732
TI  - Intergenerational and international discounting.
AB  - A discount rate for the consumption of future generations is typically composed
      of two parts. One is a "pure" time preference for immediate over postponed
      consumption, the other a declining marginal utility as consumption increases. The
      costs of greenhouse abatement, however, for at least the first 50 years, will be
      borne by the developed countries; the benefits will accrue to the presently
      undeveloped. Pure time preference always relates to one's own consumption; it has
      no relevance here. Consumption transfers over time will be from richer to poorer,
      from lower to higher marginal utility. It is a foreign aid program and it ought
      to have to compete with more direct foreign aid, which can benefit the very poor
      rather than their much-better-off descendants.

PMID- 11314733
TI  - Discounting compensation for injuries.
AB  - The reasons commonly given for discounting future costs and benefits are
      doubtfully applicable to future injuries: in particular, time preference
      justifies neither inter- nor intragenerational discounting. The cost of future
      injuries could be discounted on grounds that a smaller sum, invested at interest,
      is needed to pay a given level of ex post monetary compensation the further in
      the future the injury occurs. This effect is offset, however, by the diminishing
      marginal utility of compensation, if consumption is otherwise increasing.
      Depending on the elasticity of marginal utility of consumption, on whether
      consumption is growing at an optimal rate, and on the time period considered, the
      implicit discount rate may be positive, zero, or negative (even indefinitely so).
      There is no prospect of conventional discounting dealing appropriately with the
      cost of injuries to either future or present generations.

PMID- 11314734
TI  - Equity, efficiency, uncertainty, and the mitigation of global climate change.
AB  - Policies to mitigate potential damages from global climate change impose costs on
      the current generation to provide benefits to future generations. This article
      examines how comparisons among three stylized policies-business-as-usual,
      mitigation of climate change, and compensation for climate damages-depend on
      social preferences with respect to risk and intertemporal equity. Also examined
      is the opportunity-cost criterion, which asserts that mitigation should not be
      chosen if its net present value is smaller than that of business-as-usual.
      Analysis reveals that the discount factor used to evaluate whether mitigation
      satisfies this criterion depends on preferences regarding risk and intertemporal
      inequality of consumption, and on the risk of the compensation policy. Risk
      aversion favors mitigation over business-as-usual. If society is neutral to
      inequality, risk aversion disfavors compensation, but if society is inequality
      averse, the effect of risk aversion on preferences between compensation and
      business-as-usual is ambiguous. Inequality aversion tends to favor business-as
      usual over both alternative policies provided that, roughly speaking, the
      anticipated future improvements in welfare exceed the anticipated climate
      damages.

PMID- 11314735
TI  - Can we use human judgments to determine the discount rate?
AB  - It has been suggested that the long-term discount rate for environmental goods
      should decrease at longer delays. One justification for this suggestion is that
      human judgments support it. This article presents an experiment showing that
      judgments concerning discount rates are internally inconsistent. These results
      point to potential problems with the use of judgments referenda for determining
      discount rates in cost-benefit analyses.

PMID- 11314736
TI  - Societal response to Hurricane Mitch and intra- versus intergenerational equity
      issues: whose norms should apply?
AB  - Late in the 1998 hurricane season, Central America was slammed by a devastating
      hurricane. Honduras, Nicaragua. El Salvador, Guatemala, and Belize were greatly
      impacted by Hurricane Mitch, one of the deadliest storms to affect the region in
      the past 200 years. The economies of each of these countries were badly affected.
      In the case of Honduras-at the time the fourth-poorest country in Latin America
      its president suggested that 50 years of progress had been wiped out by the
      floods and mudslides associated with this relatively short-lived storm system.
      Humanitarian assistance poured into the region in the first months following the
      disaster. As of mid-2000, various national, bilateral, international, and
      nongovernmental programs were in progress or on the drawing board for recovery,
      reconstruction, and renewed development of the worst affected countries. Using
      Honduras as a case study, some of the ethical issues that abound in the decisions
      of whom to help, when, and how to help them in the wake of such an extreme
      climate-related human tragedy are examined. Should development assistance be
      focused on those who have been directly and adversely affected by this storm, or
      should the emphasis be on reducing the risk of exposure by future generations to
      such disasters? Is there yet another approach that seeks to protect future
      generations from similar harm while at the same time assisting present-day
      victims to get through their hardships?

PMID- 11314737
TI  - Intergenerational risk decision making: a practical example.
AB  - There is no such thing as intergenerational decision making, at least not yet. In
      fact, there is no such thing as intragenerational decision making in the context
      of maximizing overall social good given resource limitations, there are just
      decisions being made in an ad hoc fashion. Even if one assumes that there is such
      a thing as intragenerational decision making, no uniform standard or guidance
      exists to make societal decisions for the common good. Risks to society are
      judged unevenly within the same agency and across agencies. Decisions are made in
      isolation and not weighed in the societal context of what is intra or
      intergenerationally important. The National Academy of Public Administration
      (NAPA) has set forth a framework for intergenerational decision making that
      provides a consistent and fair basis for making tough decisions in order to
      address difficult issues such as the long-term disposal of nuclear wastes. NAPA
      recognizes that there is an intergenerational obligation that must encompass
      broader questions than the narrow issue of waste disposal since resources are
      finite and needs are great. The fundamental principles are based on
      sustainability with the overarching objective that "no generation should
      needlessly, now or in the future, deprive its successors of the opportunity to
      enjoy a quality of life equivalent to its own." Coupled with this objective are
      four supporting principles of trusteeship, sustainability, chain of obligation,
      and precaution. The NAPA process also recognizes that no decision can be final
      and that a "rolling future" view is better than making decisions for "all time."
      It attempts to balance the needs of the present with those of the future in an
      open and transparent process that is aimed at producing a decision, not just
      endless analysis. The U.S. Congress and president should develop a rational
      standard by which to judge laws that involve intra and intergenerational issues
      relative to the overall societal good. Present regulations need to be evaluated
      relative to a uniform level of risk and benefit to assess where the limited money
      available can do the most good for both the present and future generations in the
      context of NAPA sustainability principles. It is hoped that decision makers will
      take a serious look at this process since it can work to resolve stakeholder
      stalemate.

PMID- 11314738
TI  - Risks of hazardous waste sites versus asteroid and comet impacts: accounting for
      the discrepancies in U.S. resource allocation.
AB  - Approximately $6 billion is spent annually in the United States on the cleanup of
      sites regulated under the Comprehensive Environmental Response, Compensation and
      Liability Act (CERCLA, or Superfund). The current health risks posed by such
      sites are thought to be quite small; the expenditures are justified primarily as
      protecting hypothetical future residents of these sites. Approximately 0.05% of
      this amount, or $3 million, is spent annually by the U.S. government on the
      detection of asteroids or comets that could strike the earth. Such damaging
      impacts do occur from time to time--most recently in 1908 in an unpopulated
      region of Siberia--but no person is confirmed ever to have died as a result.
      Anticipated impacts over the course of 1 million years would yield deaths that,
      when annualized, total approximately 4,000 per year. The risk reduction goal for
      CERCLA is 15 orders of magnitude greater than that for asteroid/comet detection.
      A modest increase in resources devoted to asteroid detection would greatly
      increase the chances of early detection of a threatening object, allowing an
      effective defense to be attempted. This article argues that the much lower risk
      to-resources ratio for CERCLA cleanups than for asteroid and comet detection can
      be explained by four primary factors: (1) the regard for future generations,
      since CERCLA benefits mainly the unborn; (2) concrete fears, since toxics are
      much more feared than asteroids or comets; (3) the source of the threat, since
      toxic contamination is caused by human beings, unlike impacts from space objects;
      and (4) the greater political constituencies for hazardous waste cleanup than for
      space object detection.

PMID- 11314739
TI  - Ecological risks and community perceptions of fairness and justice: a cross
      cultural model.
AB  - Intergenerational justice is implicit in international commitments to
      sustainability. If ecological, economic, and social components of sustainability
      are to be achieved, there is a necessity for intergenerational justice
      considerations to be included in decision making. The present generation's risk
      judgments should include consideration of the possible outcomes for their
      children. But intergenerational issues cannot be considered in isolation from
      other current risk and fairness concerns. This article reports on a community
      based integrative model that describes justice and other attitudes and
      motivations that determine community and individual proenvironmental behavior in
      two nations: Germany and Australia. This model can account for a considerable
      amount of the variance in political compliance as well as various
      proenvironmental behaviors. Group or individual self-interests have nearly no
      effects on global protective behavior. It is shown that universal as well as
      contextual principles, including distributive (within or between generations),
      procedural, and interactive justice, play a crucial role in fairness judgments.
      Other principles are also taken into account, such as efficiency, environmental
      rights, and rights to economic welfare. The results are discussed in relation to
      the importance of complex community fairness judgments in predicting and
      evaluating acceptance of political decisions, and for promoting proenvironmental
      behavior.

PMID- 11314740
TI  - Voluntary siting and equity: the MRS facility experience in Native America.
AB  - This article focuses on aspects of intragenerational and intergenerational equity
      in the context of a unique policy experiment: the effort of the U.S. government
      to site a monitored, retrievable storage (MRS) facility for high-level civilian
      nuclear waste. This process and its outcomes are examined from both normative and
      subjective perspectives. While the MRS siting process was designed to be
      equitable, its eventual focus on Native American communities raises profound
      questions about environmental justice, as well as procedural, outcome, and
      intergenerational equity in cross-cultural contexts. The diverse reactions among
      Native American tribes demonstrate that translating theoretical concepts of
      equity into practice is an extraordinarily complex exercise. The MRS siting
      process, instead of being a bold policy experiment that promoted equity, emerges
      substantially flawed after its implementation in the Native American context.

PMID- 11314742
TI  - The effect of prolactin and bromocriptine on human peripheral immune status.
AB  - The aim of this study was to determine the influence of elevated serum prolactin
      (PRL) levels on the peripheral lymphocyte subsets in patients with
      hyperprolactinemia. For this purpose we studied 20 hyperprolactinemic patient
      lymphocyte subsets by flow cytometry on their hyperprolactinemic state and after
      their serum prolactin concentration was normalized with bromocriptine (BC) alone
      or BC and surgery. We observed decreased absolute numbers and percentage of
      Natural Killer (p=0.0009 and 0.0001, respectively) and CD3/CD25 lymphocytes (p =
      0.009 and 0.002) in hyperprolactinemic patients, compared to 8 sex- and age
      matched normal controls. There was no correlation between PRL levels and CD16/56
      and CD3/CD25 numbers (p=0.72 and 0.33, respectively). We did not find any
      significant difference in absolute numbers (p = 0.95) and percentage (p = 0.84)
      of B-lymphocytes of hyperprolactinemic patients, as compared with normal
      controls. We did not detect any increase in absolute cell numbers of CD16/CD56 (p
      = 0.21) and CD3/CD25 (p = 0.61) of BC-treated patients when compared to their
      hyperprolactinemic state. We demonstrated an increase in CD8-cells (p = 0.0173)
      and a decrease in CD4/CD8 ratio (p = 0.036) in hyperprolactinemic patients
      treated with BC. There was also an increase in the number of activated T-cells
      (CD3/HLA DR) in this group, compared to normal controls and the
      hyperprolactinemic state of the same patients (p = 0.04). In conclusion, elevated
      PRL levels do not lead to an "overstimulation" of the B-cells, but deteriorate
      the cytotoxic function.

PMID- 11314741
TI  - Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like
      growth factor-I system in dementia.
AB  - Changes in the hypothalamus-pituitary-adrenal axis (HPAA) function, entailing
      elevated cortisol circulating titres, occur in aging and in some neurological
      conditions, such as Alzheimer's disease (AD). Excess cortisol has neurotoxic
      effects which affect hippocampal neurones. Dehydroepiandrosterone sulphate
      (DHEAS) has an antiglucocorticoid activity and neuroprotective effects, but its
      levels decrease with aging. Glucocorticoids influence the production of insulin
      like growth factor-I (IGF-I) and modify its systemic and neurotrophic biological
      activity by inducing changes in IGF-binding proteins (IGFBPs). We looked for
      relationships between cortisol, DHEAS levels, and IGF-I - IGFBPs system in AD.
      Cortisol, DHEAS and GH levels at 02:00, 08:00, 14:00, 20:00 h, basal IGF-I, IGFBP
      1 and IGFBP-3 levels were determined by RIAs or IRMA in 25 AD patients, aged 58
      89 yr, and in 12 age-matched healthy controls. AD subjects had higher cortisol,
      lower DHEAS levels and increased cortisol/DHEAS ratio (C/Dr) than controls. In AD
      cases, total IGF-I, IGFBP-3, and IGF-I/IGFBP ratios were significantly lowered,
      while IGFBP-1 levels were significantly higher than in controls. We found a
      significant inverse correlation between IGF-I and IGFBP-3 levels vs C/Dr, and
      between both IGF-I/IGFBPs ratios vs mean cortisol levels. IGFBP-3 correlated
      directly with DHEAS. Cortisol was directly and IGF-I inversely correlated with
      cognitive impairment. In AD patients we found that alterations in HPAA function
      and elevated C/Dr are related to lowered total and free IGF-I levels. These
      findings and their relationship to cognitive impairment suggest that changes in
      hormonal set-up might influence the clinical presentation of the disease.

PMID- 11314743
TI  - High-dose intravenous corticosteroid therapy for Graves' ophthalmopathy.
AB  - In order to compare oral and high-dose iv corticosteroid therapy for Graves'
      disease, 25 patients with Graves' ophthalmopathy were treated with two weekly iv
      injections of 1 g of methylprednisolone diluted in 250-500 ml of physiological
      solution for 6 weeks, and were compared to a group of 26 patients treated with
      oral prednisone at a dose of 60-80 mg/day progressively reduced every 2 weeks for
      a total duration of 4-6 months. The efficacy of treatment was evaluated using the
      ophthalmopathy index score. Patients were followed at 3, 6, 12 months, and
      afterwards yearly. All patients showed a significant improvement in signs and
      symptoms of orbital inflammation and a slight improvement in proptosis and
      diplopia. Relevant side-effects were reported from patients receiving oral
      therapy, but no significant side-effects were observed in patients treated with
      high iv doses; a few cases presented with gastric pain (highly sensitive to
      aluminium oxide or ranitidine), while most of the patients referred to cutaneous
      rashes and a metal taste that disappeared some hours after the infusion.
      Improvements observed after treatment have been stable in both groups. In
      conclusion, in addition to a lower incidence of side-effects compared to the
      classic oral therapy, the high-dose iv steroid therapy provides efficient and
      stable improvement in Graves' ophthalmopathy.

PMID- 11314744
TI  - Relationships between personality disorders and anthropometry, hormones and
      metabolism in women.
AB  - This study sought to examine the potential influence of personality disorders
      (PD) on anthropometry, hormones and metabolism in women. In a population sample
      of women born in 1956 (no.=270), estimates of PD:s by Structured Clinical
      Interview for DSM-III-R, Axis II, were correlated with anthropometric, endocrine,
      and metabolic factors. The PD:s were grouped into three thematic clusters:
      cluster A (characterized by oddness or eccentricity), cluster B (characterized by
      self-centeredness, emotionality, and erratic behavior) and cluster C
      (characterized by anxiety and fear). Subjects with cluster A PD:s had
      significantly increased body mass index (BMI, kg/m2) and abdominal sagittal
      diameter (cm) as well as lower salivary cortisol after dexamethasone (DEX)
      compared to controls. Subjects with cluster B also had a significantly higher
      abdominal sagittal diameter and significantly lower salivary cortisol levels
      after DEX than controls. In addition, subjects with cluster B PD:s had decreased
      levels of ACTH, and significantly higher concentrations of lactate and
      triglycerides, while high-density lipoprotein (HDL) cholesterol was significantly
      lower compared to controls. A significantly higher waist/hip ratio was seen among
      subjects with cluster C PD:s. In addition, these subjects had higher levels of
      insulin, glucose, lactate, triglycerides, total cholesterol and low-density
      lipoprotein (LDL) cholesterol than controls. Moreover, IGF-I and HDL cholesterol
      were significantly decreased in the former group. These results suggest that PD:s
      are involved in the development of obesity and abdominal fat accumulation in
      women, with different endocrine and metabolic profiles depending on the type of
      PD.

PMID- 11314745
TI  - Age and gender specific stimulation of creatine kinase specific activity by
      gonadal steroids in human bone-derived cells in culture.
AB  - We previously reported a non-enzymatic method for isolation of human bone cells
      in culture that display osteoblastic features and respond to 1,25 dihydroxy
      vitamin D (1,25) and to parathyroid hormone (PTH). The present study was
      undertaken to analyze the response of cultured human bone cells to 17beta
      estradiol (E2) and to dihydrotestosterone (DHT) as a function of gender and age.
      Cultured human bone cells, obtained from biopsies during orthopedic surgery, were
      divided into four groups defined by gender and age: pre- and post-menopausal
      healthy non-osteoporotic women that were not under hormone replacement therapy
      (HRT) and mature (<55-year-old) and older (>60-year-old) men. We found gender
      specific responses to gonadal steroids using the specific activity of the brain
      type (BB) isozyme of creatine kinase (CK) as a response marker. Constitutive
      levels of CK activity did not change with age or gender and the enzyme extracted
      from cells from the different sexes and ages did not respond to either
      progesterone (P) or to 1,25. CK from the different cells responded to gonadal
      steroids in a gender specific manner, i.e. CK from female derived cells responded
      to E2 only and the enzyme from male derived cells responded to DHT only. In
      female derived cells the response to E2 declined significantly with age, while
      the response to DHT in CK from male derived cells did not vary with age. This may
      be due to either decreased proportion of mature osteoblasts and/or their
      differentiation state and/or changes in the levels of estrogen receptor(s),
      coactivators or corepressors in these cells. These results extend our knowledge
      of human osteoblast biology (beyond murine cells) and are therefore more relevant
      for developing models for treatment of human metabolic bone diseases such as post
      menopausal osteoporosis.

PMID- 11314746
TI  - Actual stress, psychopathology and salivary cortisol levels in the irritable
      bowel syndrome (IBS).
AB  - Although irritable bowel syndrome (IBS) can be considered a biopsychological
      disorder in which an association between life stress and physiological changes
      leading to bowel irregularity is present, there is a lack of data concerning
      possible modifications of the adrenal function during the disease. The aim of the
      present study was to measure biological and psychological variables related to
      the activity of the hypothalamo-pituitary-adrenal axis in IBS patients compared
      to healthy subjects. Cortisol was measured in the saliva (obtained by a stress
      free, non invasive collection procedure) of 55 IBS outpatients and 28 matched
      controls. Moreover, each subject completed the following self-administered
      questionnaires: the Rome Burnout Inventory (RBI) in its physical (RBI-PE) and
      emotional-mental exhaustion (RBI-EME) components, Beck Depression Inventory,
      State and Trait Anxiety Inventory (STAI), Perceived Social Support Scale (PSSS)
      and a Scale for the Assessment of Perceived Actual Work-Non Work Stress. Compared
      with controls, IBS subjects showed significantly higher levels of cortisol in the
      morning and lower in the evening, while they maintained the physiological
      circadian fluctuation (i.e. cortisol morning level higher than in the evening).
      Moreover, IBS patients presented a significant difference from controls in RBI-PE
      scores, which confirms the presence of fatigue, a symptom frequently reported by
      the patients. Compared with controls, no differences were found in IBS patients
      with respect to other psychological parameters. These findings suggest a
      dysregulation of the adrenal activity in IBS patients. The results may be
      relevant considering that changes in cortisol levels have been shown to be
      sensitive indicators of psychosocial stress and coping patterns in both
      laboratory and life situations.

PMID- 11314747
TI  - Thyrotropin dysregulation during a non-thyroidal illness: transient hypothalamic
      hypothyroidism?
AB  - Both the basal TSH concentration and the TSH response to iv TRH administration
      are noted to be decreased at the peak of an acute critical illness. Moreover, an
      impaired release from hypothalamus has been documented in rats with uncontrolled
      diabetes, suggesting hypothalamic dysfunction in a non-thyroidal illness.
      However, the exact inference and mechanism of this impaired TSH secretary pattern
      is not well defined in humans during a non-thyroidal illness. Therefore, this
      study assessed hypothalamic pituitary thyroid axis by determination by T4, T3,
      and T3 resin uptake prior to and TSH concentrations, prior to, as well as
      following, iv TRH administration at an interval of 30 min up to 2 hours on three
      successive mornings during a severe, critical, fatal illness in five previously
      known euthyroid subjects. TSH response to iv TRH administration was expressed as
      a maximal absolute change (delta TSH) and a cumulative response (CR TSH),
      calculated as the sum of changes from the basal level at each specific time
      period for up to 120 min. Serum T4, T3 and TSH concentrations on day 1 of the TRH
      administration were significantly lower than normal values as well as the values
      documented previously in the same individuals prior to hospitalization. T3 resin
      uptake was increased simultaneously. Moreover, serum T4, T3, and T3 resin uptake
      remained significantly unaltered on three successive days of iv TRH
      administration. However, basal serum TSH rose significantly with a parallel TSH
      response to iv TRH administration, as reflected by a progressive rise in delta
      TSH as well as CR TSH over this three-day period, with normalization of the TSH
      responses by the third day. Therefore, impaired TSH secretary pattern and altered
      thyroid hormone concentrations noted in subjects with acute critical illness may
      be attributed to the presence of a transient hypothalamic hypothyroidism.

PMID- 11314748
TI  - Cabergoline-induced CSF rhinorrhea in patients with macroprolactinoma. Report of
      three cases.
AB  - induces the macroprolactinoma shrinkage. Endoscopic transsphenoidal surgery
      offers a safe, minimally invasive and efficient management of this complication,
      which allows to regularly perform the following steps of the therapeutical
      strategy against the prolactinoma.

PMID- 11314749
TI  - Graves' disease presenting as hemiparkinsonism.

PMID- 11314750
TI  - Lymphocytic hypophysitis: report of an unusual case of a rare disorder.
AB  - A 36-year-old non-pregnant woman presented with a four-month history of
      progressive visual deterioration and amenorrhea. The latest gestation was 6 years
      earlier. Hormonal study revealed central diabetes insipidus, hypopituitarism, and
      slightly increased prolactin level. Ophthalmologic examination showed bilateral
      hemianopsia. In the magnetic resonance imaging an intrasellar mass with supra and
      retrosellar extension was found. The mass showed a polylobular aspect with
      heterogeneous signal within the tissue. The normal neurohypophysis could not be
      identified. Pterional craniotomy was performed. The pathological examinations
      revealed fibrous tissue with heavy inflammatory infiltrate composed of
      lymphocytes and plasma cells, islands of eosinophilic epithelial cells stained
      positively for chromogranin, GH, ACTH, and PRL and negatively for antibodies
      directed against HLA-II antigens. This case of lymphocytic hypophysitis was not
      related to pregnancy and involved the neurohypophysis. We discuss the features
      that can help to make a preoperative differential diagnosis.

PMID- 11314751
TI  - Management of thyroglobulin positive/whole-body scan negative: is Tg
      positive/131I therapy useful?

PMID- 11314752
TI  - Clinical application of 5alpha-reductase inhibitors.
AB  - The inhibitors of 5alpha-reductase isoenzymes (1 and 2) can be schematically
      divided in three groups according they substrate specificity: a) pure or
      preferential inhibitor of 5alpha-reductase 1; b) pure or preferential inhibitor
      of 5alpha-reductase 2; c) dual inhibitors. Despite the fact that several
      steroidal and non-steroidal inhibitors have been synthesized and experimented in
      pharmacological models, only finasteride has been extensively used for clinical
      purposes. The largest application of finasteride in man has been human benign
      prostative hyperplasia (BPH). In addition, finasteride has been recently used for
      treatment of male baldness with a 50% of objective response. In women,
      finasteride has been used in some control trials for treatment of hirsutism with
      an objective favorable response. In conclusion, finasteride appears be useful for
      BPH, baldness and hirsutism (with caution) treatment. On the basis of
      experimental observations on distribution of 1 and 2 isoenzymes in human skin,
      scalp and prostate, the dual inhibitors should be more indicated for treatment of
      BPH and baldness. Similarly, the dual inhibitors seem indicated in attempting to
      prevent prostatic cancer. The pure 5alpha-reductase 1 inhibitors seem the ideal
      drugs for treatment of acne and hirsutism.

PMID- 11314753
TI  - Triiodothyronine predominant Graves' disease in a South-East Asian population:
      prevalence and clinical significance.

PMID- 11314754
TI  - "The obese Etruscan".

PMID- 11314755
TI  - ApeI/Ref-I expression and cellular localization in human thyroid carcinoma cell
      lines.
AB  - For its DNA repair, transcription factor regulation and anti-apoptotic activity,
      the apurinic/apirimidinic ApeI/Ref-I endonuclease is thought to play a relevant
      role in human tumorigenesis. In human thyroid tumors, we demonstrated an altered
      nuclear/cytoplasmic ratio in all the carcinomas examined but not in follicular
      adenomas. In this study, Ref-I expression and cellular localization were analyzed
      in a series of human thyroid carcinoma cell lines. We found a reduced
      nuclear/cytoplasmic ratio in BCPAP, TPC I and ARO cells and not in WRO cells.
      Such a pattern of expression corresponds to that observed in thyroid tumoral
      tissues except for the WRO cells which behave as the follicular adenomas rather
      than carcinomas. Thus, these cell lines represent an excellent in vitro model to
      analyze the molecular mechanisms involved in Ref-I regulation and activity and
      clarify its role in thyroid tumorigenesis.

PMID- 11314756
TI  - Binding of 125I-labeled ghrelin to membranes from human hypothalamus and
      pituitary gland.
AB  - Ghrelin has been proposed as a natural ligand of the GH secretagogue receptor(s)
      (GHS-R), which was an orphan receptor activated by synthetic peptidyl (hexarelin)
      and non-peptidyl (MK-0677) GHS to strongly release GH in animals and humans.
      Herein we studied: 1) the binding of 125I-labeled human ghrelin to membranes from
      human hypothalamus and pituitary gland; 2) the ability of human ghrelin (either
      octanoylated or desoctanoylated), as well as of some GHS and neuropeptides to
      compete with the radioligand. The saturation binding analysis showed, in both
      tissues, the existence of a single class of high-affinity binding sites with
      limited binding capacity. The Bmax (maximal number of binding sites) values of
      ghrelin receptors in the hypothalamus were significantly greater (p<0.001) than
      those detected in the pituitary, whereas the Kd (dissociation constant) values in
      the two tissues were similar. 125I-ghrelin bound to hypothalamic membranes was
      displaced by ghrelin, hexarelin, MK-0677, various GHS antagonists (EP-80317, [D
      Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P) and some natural (cortistatin-14) and
      synthetic (vapreotide) SRIH-14 agonists. In contrast, no competition was seen in
      the presence of GHRH-44, SRIH-14 or desoctanoylated ghrelin, a ghrelin precursor
      that is devoid of GH-releasing properties. In conclusion, this preliminary study
      firstly demonstrates that ghrelin needs octanoylation to bind its hypothalamo
      pituitary receptors. These receptors are the specific binding sites for GHS and
      their antagonists, as well as for SRIH analogs (vapreotide and cortistatin- 14),
      but not for native SRIH.

PMID- 11314757
TI  - Is there a role for functional radionuclide imaging in the diagnosis of senile
      dementia?

PMID- 11314758
TI  - 99Tc(m) labelled HL91 versus computed tomography and biopsy for the visualization
      of tumour recurrence of squamous head and neck carcinoma.
AB  - This phase I pilot study reports on (1) the safety and feasibility of 99Tc(m)
      HL91, an amine oxime core radioligand that has shown oxygen dependent binding,
      and imaging; and (2) its usefulness for the visualization of local tumour
      recurrence of a biopsy proven squamous cell carcinoma of the head and neck
      (SCCHN) as compared to spiral computed tomogaphy (CT) and biopsy. Nine men (mean
      age 33 years, range 34-74 years) were prospectively included. For safety
      measurements, vital signs were recorded and serum chemical analysis carried out,
      with a complete blood cell count and urine analysis, and an ECG was performed
      prior to injection of 99Tc(m)-HL91 and repeated during the investigation. Single
      photon emission computed tomography (SPECT) scans of the head and neck, and of a
      standard, were performed at 2 h and 4 h post-injection of 740 MBq 99Tc(m)-HL91.
      Tumour-to-normal tissue background (T/N) ratios and percentage uptake were
      measured for all 99Tc(m)-HL91 scans. Spiral CT scans were obtained using a
      Somaton 4+ Siemens scanner within 1 week from the 99Tc(m)-HL91 scans. Based on CT
      and the 99Tc(m)-HL91 scan findings guided biopsies were performed. No adverse or
      subjective side effects were noticed. Vital signs, ECG findings, clinical
      laboratory, blood and urine assays remained stable in all patients. Spiral CT
      suggested local recurrence in 5/9 patients accompanied by nodal involvement in
      three, all of which proved positive on biopsy. 99Tc(m)-HL91 scintigraphy was
      false positive in one patient and true positive (TP) in 3/5 local recurrences and
      two out of three sites of lymph node involvement depicted by spiral CT. The mean
      T/N ratios at 2 h and 4 h in TPs were 1.28 (range 1.1-1.66) and 1.40 (range 1.0
      1.6), respectively. The corresponding absolute percentages of 99Tc(m)-HL91
      lesional uptake at 2 h and 4 h were mu = 0.05% (SD = 0.03%) and mu = 0.048% (SD =
      0.035%). The findings suggest 99Tc(m)-HL91 is a safe radioligand and that
      metabolic binding in a large fraction but not all of local SCCHN recurrences may
      be expected. The inference that tumour 99Tc(m)-HL91 avidity could be a non
      invasive measure of tumour hypoxia deserves however independent confirmation with
      needle oximetry.

PMID- 11314759
TI  - Effect of imaging time on gallium renal scan.
AB  - AIM: Gallium renal imaging has been reported to be useful in monitoring disease
      activity and predicting the response to therapy in lupus nephritis. Gallium renal
      images are usually obtained 48 h after the injection of 67Ga citrate, but 72-h
      images sometimes are the only available pictures. The aim of the present study
      was to determine whether the time intervals from injection to imaging had any
      effect on the grading of gallium renal scintigraphy. METHODS: Fifty-five patients
      with lupus nephritis underwent gallium renal imaging at both 48 h and 72 h post
      injection of 111 MBq of 67Ga citrate. The relative uptakes of 67Ga by the kidneys
      and the spine was judged visually on the analog images. Renal uptake was rated on
      a scale of 0-3. RESULTS: Fifty-three patients (96.3%) had the same grading of
      renal uptake in the 48-h and the 72-h images. Only two patients (3.7%) had a
      different grading in the 72-h images when compared to the 48-h images. The
      correlation between the 48-h renal uptake and 72-h renal uptake was excellent,
      with a Spearman R value of 0.94. No significant difference was noted between
      these two groups, with a P value of 0.76 (using a Wilcoxon matched pairs test).
      CONCLUSION: A gallium renal scan can be obtained either 48 h or 72 h after
      injecting 67Ga citrate. The imaging time did not interfere with the grading of
      renal uptake in lupus nephritis.

PMID- 11314760
TI  - Assessment of left ventricular function by 201Tl SPECT using left ventricular
      cavity-to-myocardium count ratio.
AB  - Equilibrium radionuclide angiography (ERNA) is the 'gold standard' for assessing
      left ventricular ejection fraction (LVEF). The aim of the study was to determine
      whether the left ventricular cavity-to-myocardium count ratio (LVCMR) from 201Tl
      myocardial single photon emission computed tomography (SPECT) correlated with
      LVEF assessed by ERNA. The study group included 159 consecutive patients (117
      male, 42 female), aged 59+/-12 years, who underwent both 201Tl SPECT and ERNA at
      rest on the same day. The LVCMR was calculated from a mid-ventricular short axis
      slice on redistribution studies, using two regions of interest (ROIs). One ROI
      was placed in the centre of the left ventricular cavity (C) and the other was
      placed in the myocardium with maximum uptake (Mmax): LVCMR= (C/Mmax) x 100. The
      correlation between LVCMR and LVEF was r = 0.85 (y = 0.943x+5.002; P < 0.0001).
      The mean calculated values +/- 1 SD were LVCMR=54+/-16% and LVEF=52+/-15%. In
      conclusion, LVCMR from 201Tl SPECT studies was closely correlated with LVEF from
      ERNA studies and can be used to easily and rapidly estimate left ventricular
      function.

PMID- 11314761
TI  - Detection of coronary artery disease by stress thallium scintigraphy in diabetic
      patients.
AB  - We investigated the efficacy of exercise stress thallium in the diagnosis of
      coronary artery disease in patients with diabetes mellitus. Forty-three patients
      with known diabetes and suspected of having coronary artery disease were included
      in the study. All the patients underwent coronary angiography, 24 had significant
      coronary artery stenosis and 19 had normal coronaries. Out of the 24 patients
      with a positive angiographic finding, thallium scintigraphy was positive in 21
      patients (sensitivity, 87.5%); and false negative in only three of the 24
      patients. Out of the 19 patients with normal angiography findings, 16 patients
      had a normal thallium scan (specificity, 84.2%) and the remaining three had a
      positive thallium scan. This gives thallium scintigraphy a positive predictive
      value of 87.5% and negative predictive value of 84.2% when compared with coronary
      angiography. The findings of this study suggest that stress thallium scintigraphy
      is a useful modality in screening of coronary artery disease in diabetic
      patients.

PMID- 11314762
TI  - Post-synchronized scintigraphic data to estimate antral motility.
AB  - We evaluated an improved dynamic antral scintigraphy (DAS) technique, without any
      frequency filtering or computation of an autocorrelation function. This DAS was
      performed in 15 consecutive patients and 10 healthy volunteers. Antral frequency
      was first estimated and was given as an input parameter to compute phase and
      amplitude values in each antral pixel. Motility indices were calculated by
      multiplying the frequency by a normalized amplitude in the whole antrum. In
      addition, a gastric emptying (GE) test was performed. Only 10 patients had a
      delayed GE when using a cut-off value of the mean of half emptying time (T +2SD)
      obtained in controls. Antral frequencies were significantly increased but
      motility indices were significantly lower in patients than in controls. These
      results in patients were accounted for by a retention of food in the antrum.
      Therefore, amplitude normalization by the antral mean count activity of each set
      of data was essential for discriminating between patients and controls and
      normalized indices appeared early predictors of hypomotility in patients with
      normal GE. This improved DAS technique should be a useful tool to assess antral
      dysmotility noninvasively, and may be of physiological and clinical interest.

PMID- 11314763
TI  - Tumour detectability in 2-dimensional and 3-dimensional positron emission
      tomography using the SET-2400W: a phantom study.
AB  - The purpose of this study was to investigate the detectability of small hot
      lesions in 2-dimensional transmission+emission (2D T/E), 2-dimensional
      simultaneous transmission+emission (2D simultaneous T/E) and 3-dimensional
      transmission+emission (3D T/E) acquisition modes in an 18F-fluorodeoxyglucose
      positron emission tomography (FDG PET) scan. The correlation between target
      detectability, target size, target to non-target uptake ratio (T/N ratio), and
      standardized uptake value (SUV) were studied. Small hot lesions ranging from 4.4
      mm to 36.9 mm in diameter were set in a cylindrical phantom. The images of
      phantoms with T/N ratios of 2.0, 4.0, 6.0, 8.0, 9.6, 13.2, 17.5, 23.8 and 30.3
      were obtained in 2D T/E, 2D simultaneous T/E and 3D T/E scans. Tumour uptake of 2
      [18F]fluoro-2-deoxy-d-glucose (FDG) in a rabbit bearing VX-2 tumours was also
      studied in 2D T/E, 2D simultaneous T/E and 3D T/E scans. The target with a
      diameter > 10.6 mm and an actual T/N ratio from 6.0 to 30.3 could be identified
      on the images obtained with all the 2D T/E, 2D simultaneous T/E and 3D T/E
      acquisition modes. The detectability efficiency of a small hot target was found
      to be 77.8% in 2D T/E and 3D T/E, but 75.9% in 2D simultaneous T/E. The T/N ratio
      and recovery coefficient (RC) of the target from the 2D simultaneous T/E image
      was very similar to that from 2D T/E, and the SUV of the target from the 2D T/E
      image was almost the same as that from the 2D simultaneous T/E and 3D T/E images.
      This study indicated that 2D simultaneous T/E scanning and 3D T/E had similar
      abilities for detecting the tumour as did 2D T/E scanning. 2D T/E, 2D
      simultaneous T/E and 3D T/E scanning had the same feasibility for semi
      quantitative analysis using SUV, as well as using the T/N ratios for 2D T/E and
      2D simultaneous T/E. In contrast, the use of the T/N ratio in 3D T/E scanning
      gave an inferior result in semi-quantative analysis, although there might have
      been an improvement if a scatter correction had been performed.

PMID- 11314764
TI  - 99Tc(m) nanocolloid scintigraphy: a reliable way to detect active joint disease
      in patients with peripheral joint pain.
AB  - We evaluated 99Tc(m) nanocolloid (NC) scintigraphy as a method for identifying
      patients with active joint disease in a group with peripheral joint pain of
      varying aetiology. Fifty-nine patients with peripheral joint pain were divided
      into two groups: those with clinical signs of active joint inflammation and those
      without objective signs. Thirty-four patients clinically diagnosed as having
      active joint disease had a total of 117 joints (95 large and 22 small) involved.
      99Tc(m) NC identified 96 (79 large and 17 small) of these joints. Twenty-five
      patients were negative clinically. Twenty-two of these were scan negative. The
      other three had a total of 11 scan positive joints. The correlation coefficient
      between clinical and scan findings was 0.79. There was no significant difference
      shown between clinical evaluation and scintigraphy (z=-1.64, P = 0.1004). 99Tc(m)
      NC proved to be an effective method for identifying patients with active
      peripheral joint disease from among a group with arthralgia.

PMID- 11314765
TI  - Thalamic asymmetry on interictal SPECT in patients with frontal lobe epilepsy.
AB  - BACKGROUND: Interictal brain single photon emission computed tomography (SPECT)
      is useful for the detection of seizure focus. Recent reports indicate a
      hypoperfusion in the ipsilateral thalamus as a seizure focus on interictal SPECT
      in temporal lobe epilepsy. In frontal lobe epilepsy (FLE), however, the
      alteration of perfusion in the thalamus has not been well documented. This study
      aimed to assess whether perfusion analysis on the thalamus may add useful
      information for the detection of epileptic foci in patients with FLE. METHODS:
      Interictal brain SPECT was performed in 11 patients with FLE. The asymmetry index
      for the thalamus and frontal area in the SPECT image was calculated in order to
      compare the laterality of the seizure foci. RESULTS: Thalamic asymmetry was seen
      in seven patients (64%), while cortial asymmetry was seen in six patients (55%).
      The concordance with the lateralization of the seizure foci was 6/7 (86%) in the
      thalamus, and 4/6 (67%) in the frontal area. Four patients showed only thalamic
      asymmetry. Concordance with the lateralization of the seizure focus was found in
      all of them. CONCLUSION: These preliminary results suggest that hypoperfusion in
      the thalamus may have a complementary role to lateralize the epileptic foci in
      patients with FLE.

PMID- 11314766
TI  - Value of combined 67Ga and 99Tc(m)-human immunoglobulin G whole-body scanning in
      malignant lymphoma.
AB  - Human immunoglobulin G labelled with 99Tc(m) (99Tc(m)-HIG) is an agent introduced
      for the localization of inflammatory lesions. There is also a limited number of
      reports concerning the uptake of this agent by malignant lesions. The aim of this
      study was to evaluate the uptake of 99Tc(m)-HIG by lymphoma. Twenty-three
      patients (five female, 18 male) with known Hodgkin's or non-Hodgkin's lymphoma
      for a period of 2-6 years (mean 4.2 years) and which, by using computed
      tomography (CT), showed recurrence, were included in the study. The patients were
      aged between 32 and 68 years (mean 38 +/- 5 years). No evidence of inflammation
      or infection was seen in any of these patients. CT, 99Tc(m)-HIG and a 67Ga scan
      were performed in the same week. CT showed abdominal involvement in 17 patients,
      pelvic involvement in 11, and thorax involvement in 11. 99Tc(m)-HIG showed higher
      sensitivity (94.1%) in the abdomen, a similar sensitivity (63.6%) in thorax, but
      lower (18.1%) in pelvic area than for 67Ga. 99Tc(m)-HIG was found to be more
      useful for the evaluation of abdominal involvement compared to 67Ga due to
      gastrointestinal excretion of the latter. The resolution of 67Ga was better than
      99Tc(m)-HIG in thorax and pelvis. Using 99Tc(m)-HIG and 67Ga together in lymphoma
      may increase sensitivity.

PMID- 11314767
TI  - Physiological significance of the rate constants in compartmental analysis.
AB  - Transfer (rate) constants in compartmental analysis are generally considered
      solely in operational terms, and little attention has been paid to their
      physiological interpretation. In this study we have examined the significance of
      their roles in physiological terms and the implications of this interpretation.
      When freely diffusible tracers are introduced into the blood stream by bolus
      injection, the sum of the exit rate constants from the blood compartment gives
      the number of blood volumes turned over per unit time; when multiplied by the
      blood volume, this value is the cardiac output. When corrected for body weight,
      the product yields the cardiac index, a biological constant for large mammals.
      The ratio of the rate constant supplying an organ to the exit-constant sum gives
      fractional cardiac output, and when multiplied by the cardiac output the ratio
      gives organ blood flow, independent of diffusibility. For freely diffusible
      tracers, organ blood flow can be calculated directly from the product of the
      organ rate constant and blood volume. At equilibrium and at equal concentration,
      the ratio of rate constants between adjacent compartments gives their relative
      volumes; this interpretation is fundamental when partitioning compartments for
      detailed analysis. These considerations have been validated by testing in both
      animals and man. Multiple solution sets may occur in mammillary models. Knowledge
      of the physiological interpretation of intercompartmental rate constants is of
      importance not only in model interpretation but in model validation, where this
      information serves as an independent check on model structure and its
      realization.

PMID- 11314768
TI  - The effects of stimulating protease-activated receptor-1 and -2 in A172 human
      glioblastoma.
AB  - Human glioblastoma cell line A172 expressed protease-activated receptor-1 and -2
      (PAR-1 and PAR-2). We investigated the effects of the stimulation of these
      receptors by receptor-activating agonist peptides on the Ca2+ signaling, protein
      kinase C translocation, cell morphology and cell proliferation in A172. Both PAR
      1 agonist SFLLRN and PAR-2 agonist SLIGKV induced an increase in [Ca2+]i. The
      prior treatment of A172 with PAR-2 agonist SLIGKV did not influence the [Ca2+]i
      response to PAR-1 agonist SFLLRN or thrombin, however, the prior treatment with
      PAR-1 agonist SFLLRN or thrombin completely abolished the second response to PAR
      2 agonist SLIGKV. Treatment with each agonist peptide produced thinner and fewer
      processes in A172. The PAR-2 agonist inhibited the proliferation of A172
      significantly while PAR-1 agonist did not. PKC-alpha and gamma were translocated
      from cytosol to membrane with either PAR-1 or PAR-2 stimulation, however, L was
      specifically translocated with SFLLRN, and lambda with SLIGKV, respectively.
      These results indicated that PAR-1 and PAR-2 stimulation produced a similar
      [Ca2+]i response and morphological changes in A172 glioblastoma while the effects
      on the cell proliferation and activation of PKC isozymes were distinct,
      suggesting that different signal transduction pathways were activated by these
      receptors. The uni-directional cross desensitization implies a functional linkage
      between PAR-1 and PAR-2 receptors.

PMID- 11314769
TI  - Dopaminergic mRNA expression in the intact substantia nigra of unilaterally 6
      OHDA-lesioned and grafted rats: an in situ hybridization study.
AB  - The present study was performed to investigate the influence of intrastriatal
      fetal mesencephalic grafts on dopaminergic mRNA expression in the non-lesioned
      substantia nigra pars compacta of unilaterally 6-hydroxydopamine-lesioned rats.
      The expression of dopamine transporter mRNA, synaptic vesicular monoamine
      transporter mRNA and tyrosine hydroxylase mRNA was assessed in adjacent cryostat
      sections using in situ hybridization. Rotational behavior induced by apomorphine
      and amphetamine as well as hybridization of striatal sections cut at the grafting
      coordinates were used to prove the functional recovery and the presence of
      grafted cells, respectively. After grafting, the number of rotations was
      decreased and hybridization signals overlying cells in the grafted striatum were
      detected. Mean grain densities overlying labeled neurons in the substantia nigra
      pars compacta of grafted rats were compared to those of shamgrafted rats and
      revealed differential expression of dopamine transporter mRNA, whereas synaptic
      vesicular monoamine transporter mRNA and tyrosine hydroxylase mRNA expression
      showed no difference. The results will be discussed in relation to previous in
      vitro and in vivo studies suggesting a reduction of functional dopamine
      transporter molecules in the contralateral striatum.

PMID- 11314770
TI  - Intrapallidal dopamine restores motor deficits induced by 6-hydroxydopamine in
      the rat.
AB  - To explore whether dopamine deficits in the globus pallidus have a role in
      generating the motor symptoms of Parkinson's disease, we examined the effects of
      selective intrapallidal administration of dopamine or its antagonists in rats
      unilaterally lesioned with 6-hydroxydopamine into the medial forebrain bundle.
      Either the turning behavior induced by apomorphine or the deficit in the
      performance of a skilled forelimb-reaching task was used as assay for drug
      action. Microinjection of either the D2 receptor antagonist, sulpiride, or the D1
      receptor antagonist, SCH-23390, into the dopamine-denervated pallidum
      significantly reduced apomorphine induced turning. In animals trained to perform
      a skilled forelimb-reaching task, 6-OHDA lesions caused a marked motor deficit in
      the contralateral forelimb. Intrapallidal dopamine applied either intermittently
      or continuously, restored up to 50% of the motor performance. Continuous
      application promoted a motor recovery that outlasted dopamine administration.
      These results show that lack of dopamine in the GP plays an important role in
      generating the motor symptoms caused by lesion of dopaminergic pathways.
      Moreover, motor recovery was produced by selectively injecting dopamine into the
      globus pallidus.

PMID- 11314771
TI  - Co-administration of memantine and amantadine with sub/suprathreshold doses of L
      Dopa restores motor behaviour of MPTP-treated mice.
AB  - The antiparkinsonian effects of the uncompetitive NMDA antagonists, memantine,
      amantadine and MK-801, in combination with an acute subthreshold dose of L-Dopa
      (5 mg/kg) in drug-naive MPTP-treated mice or a suprathreshold dose (20 mg/kg) in
      L-Dopa tolerant MPTP-treated mice were investigated. In the former case,
      memantine (locomotion: 3 mg/kg; rearing: 1 mg/kg) and amantadine (locomotion and
      rearing: 10 mg/kg) injected 60 min before the subthreshold dose of L-Dopa (5
      mg/kg), each induced an antiparkinsonian action in hypokinesic MPTP-treated mice
      that consisted of dose-specific, as opposed to dose-related, elevations of
      locomotion and rearing behaviour. At the same time, higher doses of memantine
      reduced further the rearing (10 and 30 mg/kg) and locomotor (30mg/kg) behaviour
      of the MPTP-treated mice. MK-801 plus L-Dopa elevated locomotion (0.1 mg/kg) but
      reduced rearing at the 0.3 mg/kg dose. In control, saline-treated mice, memantine
      (3, 10 and 30 mg/kg) and MK-801 (0.1 and 0.3 mg/kg) increased locomotor behaviour
      but decreased rearing behaviour, while amantadine produced no effects. Memantine
      increased locomotor (1 and 3 mg/kg, s.c.; 1 mg/kg dose restored activity) and
      rearing (0.3 and 3 mg/kg) activity in the L-Dopa tolerant MPTP-treated mice,
      whereas amantadine (3 and 10 mg/kg) restored both locomotor (30 mg/kg
      significantly increased locomotion but did not restore the activity level) and
      rearing (3 mg/kg only) activity. MK-801 (0.1 and 0.3 mg/kg, s.c.) also increased
      significantly locomotor activity of L-Dopa-tolerant MPTP mice although the
      antikinetic action was not reversed, thereby precluding a restorative effect of
      the compound. These results, demonstrating both a synergistic and a restorative
      effect of the NMDA antagonists in coadministration with L-Dopa, demonstrate a
      putative antiparkinson action by these compounds in a functional animal model
      that incorporates the "wearing-off" complications of L-Dopa administration in the
      disorder.

PMID- 11314772
TI  - The central catechol-O-methyltransferase inhibitor tolcapone increases striatal
      hydroxyl radical production in L-DOPA/carbidopa treated rats.
AB  - Inhibition of catechol catechol-O-methyltransferase (COMT) in the brains of
      subjects treated with L-DOPA (L-3,4-dihydroxylphenylalanine) and an aromatic
      amino acid decarboxylase (AADC) inhibitor is suggested to cause an increase of L
      DOPA, which might lead to oxidative damage through enhanced formation of free
      radicals. To investigate this hypothesis, the acute effects of two doses of the
      systemically administered COMT inhibitors entacapone (peripheral) and tolcapone
      (peripheral and central) on the extracellular formation of hydroxyl radicals in
      vivo following treatment with L-DOPA and the AADC inhibitor carbidopa were
      examined. The formation of extracellular hydroxyl radicals were determined by the
      measurement of 2,3-dihydroxybenzoic acid (2,3-DHBA), a reaction product of
      hydroxyl radicals with sodium salicylate, using microdialysis in the striatum of
      anesthetised rats. The COMT inhibitors were administered together with 50 mg/kg
      i.p. carbidopa as 5% gum arabic suspensions intraperitoneally (i.p.) at doses of
      0, 1.0, and 10 mg/kg body weight to a total of 36 male HAN-Wistars rats. L-DOPA
      was injected i.p. 40 min after drugs of interest. Microdialysis samples were
      collected every 20 min for 400 min at a perfusion rate of 1 microl/min.
      Systemically administered 10 mg/kg tolcapone, but not entacapone, induced an
      increase in hydroxyl radical formation in the striatum of anesthetised rats
      following treatment with L-DOPA/carbidopa. The increase in hydroxyl radical
      formation was reflected by higher extracellular concentrations of the hydroxylate
      product of salicylate, 2,3-DHBA, peaking at 192% of baseline at the end of the
      observation period. Similar results were also found using the AUC (area under the
      curve) value estimated for the observation period. We conclude that the increase
      in hydroxyl radical formation is likely to result from an increased rate of
      monoamine oxidase-mediated and non-enzymatic (autoxidation) dopamine metabolism
      following increased central availability caused by reduction in COMT-mediated
      metabolism. We cannot, however, exclude the possibility that hydroxyl radicals
      are produced by tolcapone as a result of uncoupling mitochondrial oxidative
      phosphorylation.

PMID- 11314773
TI  - Skin function and skin disorders in Parkinson's disease.
AB  - Cutaneous symptoms (seborrhoea and hyperhidrosis) in Parkinson's disease were
      investigated. In 70 treated patients with Parkinson's disease and 22 control
      subjects, non-invasive bioengineering methods (sebumetry, corneometry, pH) were
      carried out on the forehead, sternum and forearm. In addition, concomitant
      dermatoses and medication were recorded. 18.6% of the patients had seborrhoea on
      the forehead (>220 microg/cm2), 51.4% showed normal sebum values (100-220
      microg/cm2) and 30% a sebostasis (<100 microg/cm2). Males has significantly
      higher sebum values than females. No relationship between the seborrhoea and the
      therapy for Morbus Parkinson was found. Patients with hyperhidrosis (n = 36) had
      significantly lower pH values (p < 0.05) on the forehead than those without
      hyperhidrosis. 22 patients (31.9%) reported a cold/hot flush and a further 13
      (18.8%) had clinical rosacea. Seborrhoea is rare in treated Parkinsonian patients
      but hyperhidrosis is frequently found. Furthermore, a particular lack of
      vasostability (flush) appears to be an autonomic dysregulation in the skin
      related to Morbus Parkinson, which has not been studied to any extent to date.

PMID- 11314774
TI  - Long-term persistence of symptomatic effect of selegiline in Parkinson's disease.
      A two-months placebo-controlled withdrawal study.
AB  - Following a two-months of placebo-controlled withdrawal, the MAO-B inhibitor
      selegiline was found to maintain a long term significant mild to moderate
      symptomatic effect on bradykinesia and tremor at rest in nine patients with
      Parkinson's disease (stage II and III of H&Y), whose functional impairment had
      also required a dopaminergic therapy with low-dose bromocriptine. Both motor
      signs found worsened during the wash-out showed a full recovery to pre-withdrawal
      condition within two months after reinstitution of the drug.

PMID- 11314775
TI  - Difference in toxicity of beta-amyloid peptide with aging in relation to nerve
      growth factor content in rat brain.
AB  - Amyloid beta-peptide (Abeta) is the major constituent of the senile plaques in
      the brains of patients with Alzheimer's disease. We have demonstrated previously
      that memory impairment, dysfunction of the cholinergic and dopaminergic neuronal
      system and morphological degeneration are produced after the continuous infusion
      of Abeta into the cerebral ventricle in 8-week-old rat. In the present study, we
      investigated the toxicity of Abeta in infant (10 days old), adult (8 weeks old)
      and aged (20 months old) rats in relation to nerve growth factor (NGF) content in
      various regions of the brain. After a 2-week-infusion, choline acetyltransferase
      (ChAT) activity was significantly decreased in the hippocampus of adult, but not
      infant or aged rats. NGF levels in the hippocampus were increased only in adult
      rats. These results suggest that Abeta is toxic only in the matured adult brain,
      and that the mechanism of toxicity is related to NGF synthesis.

PMID- 11314776
TI  - Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal
      fluid of Alzheimer's disease patients.
AB  - Immunoreactivities of total apolipoprotein E (ApoE-IR), amyloid beta peptide(1
      42) (Abeta42-IR), interleukin-6 (IL-6-IR), substance P (SPIR) and total tau
      protein (TTIR) were measured in lumbar cerebrospinal fluid samples of patients
      with Alzheimer's disease (AD), non-Alzheimer's dementias (NAD), neurological
      disorders without cognitive impairment (OND) and controls without central nervous
      system disease using sensitive and specific enzyme immunoassay methods. TTIR was
      highly significantly increased (P < 0,001) and Abeta42-IR was significantly
      decreased (P < 0,001 vs. OND/CO, P < 0,03 vs. NAD) in the AD cohort compared with
      the other diagnostic groups. Significant increases in AD were also found for ApoE
      IR (P < 0,001) and IL-6 (P < 0,03), but there was a considerable overlap between
      groups. In the total AD cohort, SPIR was not significantly changed, but AD
      patients with late disease onset (>65 years) showed significantly higher values
      than both early onset patients (<65 years) and controls (P < 0,05). Discriminant
      function analysis showed that Abeta42-IR (cut-off value 375pg/ml) and TTIR (cut
      off value 440 pg/ml) levels contributed most to the group classification of
      patients. At 85% sensitivity for AD and 100% specificity for controls, the
      combined evaluation of Abeta42-IR and TTIR in this cross-sectional study resulted
      in a graph separating AD from non-AD patients with increased specificity of 91%
      and 75% for AD versus OND and NAD, respectively.

PMID- 11314777
TI  - Sputum cytopathological findings in pig farmers.
AB  - The purpose of this study is to compare the cytological changes in the
      respiratory tracts of pig farmers exposed to an environment of swine confinement
      buildings with control, non-exposed subjects living in the same geographical
      area. Spontaneously produced sputum specimens were obtained from 133 pig farmers
      and 120 control subjects, all clinically healthy, and grouped according to
      smoking habits and sex. The findings of siderophages, eosinophils, abnormal
      columnar cells and respiratory spirals were significantly more frequent in the
      pig farmers. Siderophages were noted in 25.6% of pig farmers and in 5% of control
      subjects. By logistic regression analysis, pig farming is the single predictive
      factor for siderophages and eosinophils. For other cytological abnormalities,
      except Creola bodies and granular debris, smoking is the most significant
      predictive variable, but pig farming, age and male sex also correlate with
      smoking. Atypical squamous metaplasia was observed in 11.3% of pig farmers and in
      5.8% of control subjects. These findings are in concordance with previous
      epidemiological and clinical studies and also reveal a new aspect of the harmful
      effect of pig farming exposure to the vascular and epithelial structures of the
      respiratory tract. It also demonstrates the usefulness of the simple method of
      sputum cytological analysis.

PMID- 11314778
TI  - The role of cyclin-dependent kinase inhibitor p27 in squamous cell carcinoma of
      the esophagus.
AB  - The level of p27 expression decreases during tumor development and progression.
      Loss of p27 protein provides independent prognostic information in breast,
      prostate, colon, stomach and lung carcinomas. We generated a new polyclonal
      antibody against p27 and carried out immunohistochemical analysis of p27
      expression in 61 specimens of esophageal squamous cell carcinoma, 10 carcinoma in
      situ specimens, and 5 squamous epithelial dysplasia specimens of the esophagus.
      We examined the correlation of p27 expression with various clinicopathologic
      features and prognosis. In squamous epithelial dysplasia, the p27-positive cells
      were located in the superficial normal-appearing cells, not in the atypical
      cells. In carcinoma in situ, the expression of p27 was markedly lower than in
      normal esophageal epithelium. In advanced squamous cell carcinomas, high p27
      correlated significantly with the degree of differentiation (p = 0.0002) and the
      depth of tumor invasion (p = 0.001) was statistically significant. The high p27
      expression group had a better prognosis than did the low or negative p27
      expression groups, but these differences were not statistically significant.
      These observations may imply that a decrease in p27 expression occurs early on in
      the carcinogenesis of esophageal carcinoma. In addition, p27 expression may
      correlate with the histologic differentiation of squamous cell carcinoma of the
      esophagus.

PMID- 11314779
TI  - Value of limited necropsy in HIV-positive patients.
AB  - We performed limited autopsy with histological examination of tissue cores
      obtained percutaneously using the Tru-Cut needle and the Jamshidi trocar in 150
      adult HIV-positive patients. Data were compared retrospectively with the
      antemortem clinical diagnosis. Eighty-one percent of the patients were male, and
      78% were intravenous drug users. Specimens were obtained from the brain, liver,
      lung, bone marrow, and kidney of most patients. The main findings included liver
      cirrhosis in 22 cases (associated with HCV infection in 81%), Pneumocystis
      carinii pneumonia in 21, Cytomegalovirus (CMV) infection in 19, Mycobacterium
      avium-intracellulaire (MAI) infection in 17, bacterial pneumonia in 14,
      tuberculosis in 12, and lymphoma in 13 cases. Forty-six (30.6%) patients had at
      least one clinical diagnosis that was confirmed by autopsy, i.e., there was 40.6%
      agreement between pre- and postmortem findings. Forty-six (30.6%) patients had at
      least one clinical diagnosis that was not confirmed at autopsy, whereas 41
      (27.3%) had at least one AIDS-related or unrelated disease that was not suspected
      clinically. The results obtained by limited autopsy are principally comparable to
      those achieved by full necropsy, with the advantages of decreasing the contagious
      risk, saving cost and time, including a rapid final diagnosis, and easily
      obtaining the consent for postmortem examination so that necropsy studies may be
      performed on a larger number of patients, thus contributing to a better
      understanding of the spectrum of HIV infection in our environment.

PMID- 11314780
TI  - DNA topoisomerase II-alpha in pulmonary carcinoid tumors.
AB  - Fifty-four pulmonary carcinoid tumors of surgically treated patients were
      diagnosed according to modified Arrigoni histological criteria (WHO 1999). Forty
      seven typical (TC) and seven atypical carcinoids (AC) formed the basic groups.
      Four subgroups were selected from the TCs and consisted of cases with higher
      tumor size (T2) or those associated with nodal involvement (N1), tumor
      satellites, and tumorlets. Subgroup tumors were regarded as affections with
      possible increased proliferation potential. The proliferate activity was examined
      immunohistochemically by topoisomerase II-alpha (clone SWT3D1) on paraffin
      material and calculated by the number of positive nuclei per 10 HPF. The
      topoisomerase expression was found to be statistically different in both
      principal groups made up of typical and atypical carcinoids with a mean value of
      49 and 135 positive nuclei per 10 high power field in TC and AC, respectively.
      The remaining subgroups of the TCs associated with examined characteristics
      (larger tumor diameter, metastases, satellites, tumorlets) were not found to be
      statistically different. The topoisomerase II-alpha is a marker giving valuable
      information about the diagnosis of pulmonary typical and atypical carcinoids.

PMID- 11314781
TI  - Selective culture of epithelial cells from primary breast carcinomas using
      irradiated 3T3 cells as feeder layer.
AB  - The main drawback of the selective culture of human mammary epithelial cells from
      primary breast cancer is the overgrowth of tumor-associated stromal fibroblasts.
      This drawback may be overcome by using, in primary culture, lethally irradiated
      3T3 cells which act as a feeder layer to maintain tumor-derived epithelial cell
      proliferation. These 3T3 cells, exposed to 60 Gy at confluence, form a specific
      cellular substrate which constitutes an obstacle to fibroblast attachment. Enzyme
      disaggregated breast cells from six primary breast carcinomas were cocultured
      over lethally irradiated but living 3T3 cells. The method led to the purification
      of tumor-derived epithelial cells from all six cancer samples, and long-term
      culture was obtained in one. The epithelial nature of these purified tumor
      derived epithelial cells was demonstrated by their general morphology and by the
      expression of cytokeratins and Epithelial Membrane Antigen. These results confirm
      the stimulatory effect of a this stromal feeder layer on breast epithelial cell
      growth and show that this stromal feeder layer can also control the fibroblast
      overgrowth. Our results provide an alternative approach in the selective culture
      of epithelial cells from primary breast carcinoma.

PMID- 11314782
TI  - p53 protein expression and gene mutation in phyllodes tumors of the breast.
AB  - The malignant potential of mammary phyllodes tumors is difficult to assess on
      initial pathologic examination. Studies on the p53 tumor suppressor gene have
      shown that it has an important role in the development of a variety of
      malignancies, yet the specific contribution to the pathogenesis and development
      of the malignant potential of phyllodes tumor is largely unknown. We studied p53
      protein expression in 25 cases of phyllodes tumors histologically classified as
      either malignant (12 cases) or benign (13 cases). Using microdissection approach,
      we also analyzed the p53 gene sequence in a case that demonstrated progression
      from benign to malignant phenotype. Nuclear p53 staining was detected in various
      proportions (1-90%) of neoplastic stromal cells of malignant tumors. No staining
      was found in benign tumors. Progression from benign to malignant phenotype was
      associated with a significant increase in the accumulation of p53 (more than 20
      times). This was caused by an underlying missense mutation in exon 7, resulting
      in a change from Arg248 to Trp248 in the malignant component of the tumor.
      Stromal p53 over-expression was observed only in neoplasms histologically
      classified as malignant and was associated with an increased proliferation index
      (MIB-1 staining). These two markers may be used as useful adjuncts in the
      diagnosis of malignancy in difficult cases or when only a limited sample size is
      available. Somatic mutation in exon 7 of p53 gene in malignant phyllodes tumor
      points toward the importance of p53 in the malignant transformation of phyllodes
      tumors.

PMID- 11314783
TI  - Morphometric evaluation of nucleolar organizer regions in cervical
      intraepithelial neoplasia.
AB  - The objective of this study was to determine whether some morphometric parameters
      and two different methods of counting AgNOR dots were correlated with the grade
      of cervical intraepithelial neoplasia. Thirty uterine cervix biopsies (8 cases of
      cervicitis, 9 CIN I, CIN II and 6 CIN III) were studied. Two methods were used to
      count AgNOR dots. The first one consisted of counting the number of epithelial
      cells with 1, 2, 3, 4, or more dots. The second method, based on a computer
      analysis system, consisted of counting the total number of dots in 100 cells,
      without considering the number of dots per cell. Using the same computer analysis
      system, the following parameters were measured: area, diameter, perimeter,
      roundness and length of each dot. The following parameters were found to be
      correlated with the grade of intraepithelial neoplasia: 1) number of cells with 1
      dot, which decreased with increasing grade of cervical intraepithelial neoplasia;
      2) number of cells with 4 dots or more, which increased with increasing grade of
      cervical intraepithelial neoplasia; 3) total number of dots per 100 cells, which
      progressively increased with increasing grade of intraepithelial neoplasia. We
      conclude that counting cells with 4 or more dots is the more trustworthy
      parameter for distinguishing the grade of cervical intraepithelial neoplasia.

PMID- 11314784
TI  - Infantile demyelinating neuropathy associated with a de novo point mutation on
      Ser72 in PMP22 and basal lamina onion bulbs in skin biopsy.
AB  - Codon 72 has been designated as a hot spot for distinct missense mutations in the
      peripheral myelin protein 22 (PMP22) gene. Ser72Leu substitution was associated
      with Dejerine-Sottas syndrome (DSS) in four patients and with congenital
      hypomyelination neuropathy (CHN) in one patient. Our objective was to report one
      other DSS patient with Ser72Leu substitution in PMP22 and to concurrently
      illustrate how less invasive procedures such as skin biopsy could provide a rapid
      and reliable alternative to conventional sural nerve biopsy for the
      characterization of histophenotypic features. A skin biopsy was carried out in a
      2 4/12-year-old girl with muscle atrophy, hypotonia and weakness, as well as
      generalized areflexia and absent sensory and motor nerve responses. Standard
      electron microscope techniques were used. PMP22 was screened by automated direct
      nucleotide sequencing analysis. Morphological examination revealed basal lamina
      onion bulbs surrounding a de- or hypomyelinated axon in all nerve bundles.
      Mutation analysis demonstrated a missense point mutation in codon 72 of the PMP22
      gene leading to a Ser72Leu substitution. Further genotype-phenotype correlations
      will have to determine whether morphologically distinct phenotypes can be
      correlated with specific mutations. For this purpose, cutaneous nerve bundles
      could serve as an alternative tool to help identify and classify subtypes in this
      heterogeneous syndrome.

PMID- 11314785
TI  - Longterm survival in acute rhinocerebral mucormycosis with giant cell arteritis
      and foreign body granulomas.
AB  - A case of rhinocerebral mucormycosis occurring in a 41-year-old man with insulin
      treated diabetes mellitus is reported. Microscopically, biopsy samples obtained
      from the left ethmoid and middle turbinate sinuses contained fungi that formed
      mycotic granulomas associated with multinucleate giant cell arteritis. The
      multinucleate giant cells contained broad, infrequently septate hyphase
      consistent with mucormycosis. The patient received surgical debridement with
      extenteration of the left orbit, and intravenous liposome-encapsulated
      amphotericin B. After 12 months, examination of the patient revealed complete
      healing. Multinucleate giant cell granulomas and arteritis are only exceptionally
      associated with rhinocerebral mucormycosis, but these histologic findings may be
      correlated with a progressive disease with better prognosis.

PMID- 11314786
TI  - Thymic carcinosarcoma consisting of squamous cell carcinomatous and embryonal
      rhabdomyosarcomatous components. Report of a case and review of the literature.
AB  - A case of thymic carcinosarcoma in an 83-year-old Japanese man is presented. He
      died of superior vena cava syndrome caused by a rapidly enlarged anterior
      mediastinum tumor eight months after initial symptoms. Autopsy revealed a 16 x 12
      x 25 cm-sized, tan yellow, whitish tumor with a multinodular and microcystic
      appearance located in the left anterior mediastinum, which involved the residual
      thymus. The tumor had directly invaded the left pleura, and had metastasized to
      the right lung and spleen. Histologic examinations of the primary tumor showed a
      sarcomatous component consisting of racquet- or spindle-shaped cells with cross
      striations, and small nests of atypical squamous cells scattered throughout the
      tumor; neither transition between the two components nor intermediate cells with
      both epithelial and mesenchymal features was seen. Electron microscopic and
      immunohistochemical examinations confirmed the rhabdomyomatous differentiation of
      the sarcomatoid component. To our knowledge, there have been only two reported
      cases showing histologic features similar to the present tumor. For the
      histogenesis of thymic carcinosarcoma, we propose two hypotheses. The first is
      that sarcomatous cells are derived from carcinomatous cells by tumoral
      metaplasia. Secondly, that this type of tumor originates from thymic primitive
      cells with multidirectional differentiation potential. In accordance with the
      latter, we consider that the present tumor originated from thymic primitive
      cells. Thymic carcinosarcoma is a highly malignant tumor, and most patients die
      within a year. Appropriate therapies must be developed.

PMID- 11314787
TI  - Fulminant toxoplasmosis in a heart transplant recipient.
AB  - Toxoplasma gondii infections in heart transplant recipients emerge in most cases
      as newly acquired infections of the immunocompromised sero-negative patient from
      an exogenous source, usually the donor organ. We report on a 64-year-old heart
      transplant recipient who developed pneumonitis, myocarditis, and hyperacute
      encephalitis three weeks after transplantation. Histopathological examination of
      an endomyocardial biopsy revealed fulminant T. gondii infection. Although
      appropriate chemotherapy was administered immediately, the patient died the next
      day. Our case demonstrates that if a histological diagnosis is not rendered in
      time, fulminant toxoplasmosis may lead to a fatal outcome. In conclusion, a
      general screening of the donors and recipients for opportunistic infections,
      including toxoplasmosis, and an appropriate prophylaxis should always be
      considered.

PMID- 11314788
TI  - Geometry of carriers controlling phenotypic expression in BMP-induced
      osteogenesis and chondrogenesis.
AB  - BACKGROUND: The effect of the geometry of extracellular matrices on bone
      morphogenetic protein (BMP)-induced osteogenesis has not been systematically
      studied. Geometry is crucially important for the scaffold in bone and joint
      tissue engineering. The purpose of this study was to elucidate principles of
      geometry of matrices in designing new scaffolds and matrices for use in
      reconstruction of bone and joints. METHODS: More than ten biomaterials with
      different geometries, including a unique device of honeycomb-shaped
      hydroxyapatite, were combined with BMPs of recombinant (rhBMP-2) or natural
      bovine origin (S300 BMP cocktail) and implanted subcutaneously into 4-week-old
      Wistar-King rats. The implanted pellets were removed at 1-4 weeks and analyzed
      for bone and cartilage formation by histological and biochemical methods.
      RESULTS: BMP-induced bone and cartilage induction was highly dependent on the
      geometric properties of the carrier. Some carriers such as porous particles or
      blocks of hydroxyapatite induced osteogenesis directly, without detectable
      chondrogenesis, whereas other carriers such as fibrous glass membrane induced
      cartilage exclusively. Still other carriers induced mostly cartilage followed by
      bone formation. Solid particles of hydroxyapatite and fibrous glass membrane with
      too tight a meshwork did not induce bone or cartilage. The optimal pore size for
      bone-forming efficacy in porous blocks of hydroxyapatite was a diameter of 300
      400 microm. In straight tunnel structures with various diameters in honeycomb
      shaped hydroxyapatite, tunnels with smaller diameters (90-120 microm) induced
      cartilage followed by bone formation, whereas those with larger diameters (350
      microm) induced bone formation directly within the tunnels. CONCLUSIONS: BMP
      carriers were classified into three types: bone-inducing, cartilage-inducing, and
      cartilage-bone-inducing. From the analysis of causative factors inducing
      osteogenesis and chondrogenesis in the BMP system, we concluded that the geometry
      of the carrier is crucially important and vasculature-inducing geometry should be
      considered in designing effective scaffolds for bone formation. We propose a
      classification of geometry of the artificial extracellular matrices that is
      useful for designing a scaffold for tissue engineering of bone and related
      tissues. CLINICAL RELEVANCE: Conventional requisites of the BMP carriers for
      clinical use have mainly concerned the affinities of carriers with cells and
      biomolecules and their mechanical strength. The vasculature-inducing geometry of
      carriers adds a new criterion in designing systems for effective bone and joint
      reconstruction. The geometries of porous structures-their sizes, continuity, and
      straightness as verified by hydroxyapatite in this study-will be applicable for
      other biomaterials for clinical reconstruction therapy.

PMID- 11314789
TI  - Bone induction by BMPs/OPs and related family members in primates.
AB  - BACKGROUND: In a series of studies in the primate Papio ursinus, we have examined
      the capacity of bone morphogenetic proteins (BMPs/OPs) delivered in a variety of
      biomaterial carrier systems to elicit bone formation in heterotopic and
      orthotopic sites. In this review, we compare the osteoinductive effects of
      different biomaterial delivery systems that have or have not been pretreated with
      BMPs/OPs. In particular, we focus on the geometric induction of bone formation by
      sintered porous hydroxyapatite (SPHA) discs with concavities on their planar
      surfaces, which elicit bone formation without exogenously applied BMPs/OPs.
      METHODS: Heterotopic bone formation was examined by bilaterally implanting 100-mg
      pellets of a collagenous carrier containing BMPs/OPs in the rectus abdominis
      muscle of the adult baboon. Orthotopic bone formation was examined by implanting
      1 g of a collagenous carrier containing BMPs/OPs into two full-thickness critical
      sized 25-mm-diameter defects on each side of the calvaria of adult baboons. The
      BMPs/OPs whose effects were examined included recombinant human osteogenic
      protein-1 (rhOP-1), recombinant human transforming growth factor-beta1 (rhTGF
      beta1), rhTGF-beta2, and porcine platelet derived transforming growth factor
      beta1 (pTGF-beta1). Tissue from the rectus abdominis muscle was harvested 30 or
      90 days after implantation. Tissue from the orthotopic calvarial model was
      examined at 1, 3, 6, 9, and 12 months after implantation. To demonstrate the
      effect of surface geometry on bone induction, hydroxyapatite powders were
      sintered to form solid discs with a series of concavities on the planar surfaces
      of the SPHA discs. The discs were either pretreated with exogenous rhOP-1 or not
      treated with exogenous OP-1. They were then implanted heterotopically or
      orthotopically into calvarial defects. Bone formation was evaluated
      histologically in undecalcified sections stained with Goldner's trichrome stain
      or 0.1% toluidine blue. RESULTS: Naturally derived BMPs/OPs or rhOP-1 in a
      collagenous carrier elicit heterotopic bone formation and the complete healing of
      25-mm-diameter critical-sized defects by day 90 following implantation. Binary
      applications of TGF-beta1 together with rhOP-1 in the collagen carrier induced
      massive endochondral ossicles in heterotopic sites and bone formation in
      calvarial defects. pTGF-beta1, rhTGF-beta1, and rhTGF-beta2 are powerful inducers
      of heterotopic endochondral bone formation but elicit limited bone formation in
      calvarial defects. SPHA discs pretreated with rhOP-1 elicited extensive bone
      formation in both heterotopic and orthotopic sites. However, SPHA without rhOP-1
      also elicited bone formation in heterotopic and orthotopic sites and complete
      healing of the calvarial defects. CONCLUSION: We have prepared SPHA discs with
      concavities on their planar surfaces that induce bone formation in heterotopic or
      orthotopic critical-sized calvarial defects without exogenously applied BMPs/OPs.
      This biomaterial induces bone formation by intrinsic osteoinductivity regulated
      by the geometry of the substratum. The incorporation of specific biological
      activities into biomaterials by manipulating the geometry of the substratum,
      defined as geometric induction of bone formation, may make it possible to
      engineer morphogenetic responses for therapeutic osteogenesis in clinical
      contexts. CLINICAL RELEVANCE: We have implemented a clinical trial using
      naturally derived BMPs/OPs extracted and purified from bovine bone matrices and
      implanted in craniofacial defects in humans. In addition, the discovery that
      specific geometric and surface characteristics of sintered hydroxyapatites can
      induce intrinsic osteoinductivity in primates paves the way for formulation and
      therapeutic application of porous substrata designed to obtain predictable
      intrinsic osteoinductivity in clinical contexts.

PMID- 11314790
TI  - Delivery systems for BMPs: factors contributing to protein retention at an
      application site.
AB  - BACKGROUND: Recombinant human bone morphogenetic proteins (rhBMPs) are being
      tested in clinical studies for their capacity to elicit bone formation.
      Biomaterials used in delivery systems also play a critical role in supporting the
      osteoinductive activity of BMPs, attributable to the controlled presentation of
      the BMPs to target cells. Despite extensive preclinical studies, the factors
      contributing to local rhBMP pharmacokinetics remain to be elucidated. METHODS:
      The rhBMP pharmacokinetics were studied in a rat subcutaneous implant and in an
      intramuscular injection model. In situ levels of rhBMPs were quantitated with use
      of 125I-labeled tracers. The effects of protein structural features and the
      nature of the biomaterial implant were explored. Osteoinduction by
      biomaterial+rhBMP combinations was assessed by a semiquantitative, histology
      based bone score. RESULTS: With the use of rhBMP-2, rhBMP-4, and an N-truncated
      rhBMP-2, the protein isoelectric point was found critical for the initial
      retention of rhBMPs in an implant. Osteoinduction studies carried out in parallel
      indicated that rhBMPs with a higher implant retention elicited more bone
      formation. In the clinically used collagen+rhBMP-2 device, collagen crosslinking
      and sterilization were most influential in rhBMP-2 retention. To increase
      retention at an application site, thermoreversible polymers were engineered and
      shown to enhance local rhBMP-2 retention, especially by injectable delivery.
      CONCLUSIONS: Two critical components of an osteoinductive device--namely, the
      biomaterial and the rhBMP--were shown to influence local protein pharmacokinetics
      and osteoinductive activity of the device. Designer biomaterials can provide an
      additional mechanism to modulate local protein pharmacokinetics. CLINICAL
      RELEVANCE: These studies form the foundation of next-generation osteoinductive
      devices with improved potency at sites of desired bone regeneration and reduced
      side effects at other sites.

PMID- 11314791
TI  - Augmentation of alveolar bone and dental implant osseointegration: clinical
      implications of studies with rhBMP-2.
AB  - BACKGROUND: The surgical placement of dental implants is governed primarily by
      the prosthetic design and secondarily by the morphology and quality of the
      alveolar bone. Implant placement may be difficult, if at all possible, due to
      alveolar ridge aberrations. In consequence, prosthetically dictated dental
      implant positioning often entails augmentation of the alveolar ridge and adjacent
      structures. The objective of this review is to discuss recent observations of the
      biologic potential, the clinical relevance, and the perspectives of the
      application of recombinant human bone morphogenetic protein-2 (rhBMP-2)
      technology for alveolar bone augmentation and dental implant fixation. METHODS:
      Our studies use discriminating, critical-size, supraalveolar defects in dogs to
      evaluate the biologic potential of the rhBMP-2 technology. We also use clinical
      modeling, including peri-implantitis and alveolar ridge defects and the maxillary
      sinus in preparation for clinical indications, in dogs and inhuman primates.
      RESULTS: The results suggest that rhBMP-2 has substantial potential to augment
      alveolar bone and support dental implant fixation and functional loading.
      CONCLUSION AND CLINICAL RELEVANCE: Inclusion of rhBMP-2 for alveolar bone
      augmentation and dental implant fixation will not only enhance the predictability
      of the existing clinical protocol but will also allow new approaches to these
      procedures.

PMID- 11314792
TI  - Application of bone morphogenetic proteins in the treatment of clinical oral and
      maxillofacial osseous defects.
AB  - BACKGROUND: Commonly occurring extensive osseous defects in the oral and
      maxillofacial area are seen following complete or partial resection of the
      mandible and other facial bones in oncologic surgery or following traumatic
      injury. Autogenous osseous grafts have been used to restore these defects.
      Additionally, bone graft substitute materials and autogenous osseous grafts are
      applied to congenital defects such as cleft palate, facial clefts, and facial
      asymmetry. We have simulated these types of defects in appropriately aged Macaca
      fascicularis and Macaca mulatta monkeys to study the efficacy of using bone
      morphogenetic protein (BMP) as an osseous inductor. The objective of these
      studies was to obtain information on the feasibility of employing bone inductors
      to regenerate large continuity critical-sized maxillofacial defects without using
      bone grafts. METHODS AND RESULTS: In one study, involving eight animals, the body
      of the mandible was removed, simulating hemi-mandibulectomy defects following
      traumatic bone loss or oncologic surgery. Recombinant human (rh) BMP-2 (Genetics
      Institute, Cambridge, Massachusetts) in a collagen carrier (Colla-Tec Inc.,
      Plainsboro, New Jersey) then was placed in the hemi-mandibulectomy defect with
      use of titanium orthopaedic mesh fixation (Sofamor Danek-Medtronic, Memphis,
      Tennessee). Entire bone regeneration of the defect was observed 5 and 6 months
      postoperatively. In another group of subhuman primates, the restored area was
      functionally stimulated at the 5-month post-BMP implantation level by placement
      of intraoral titanium implants. The animals were allowed to function for 8 months
      with these titanium implants. Microscopic results showed increased density, bone
      volume, and thickness of the trabecular bone pattern. The bone cortex in the
      restored defect also increased in thickness compared with the nonsurgical areas.
      To evaluate the effect of rhBMP-2 in aging individuals, a group of six Macaca
      animals over 20 years of age received the same type of mandibular resection
      followed by BMP grafting with functional stimulation by mastication on root form
      implants placed at 5 months after BMP implantation. The entire mandible
      regenerated as in the younger group of animals; therefore, age did not appear to
      be a factor in the reparative process. Thus, the number of stem cells supposedly
      reduced with increasing age did not appear to affect the overall result of BMP
      induced bone regeneration. Additionally, in applying the inductor material to
      younger monkeys (1-1 1/2 years of age), the rhBMP-2 was placed in simulated
      bilateral cleft palate defects. On one side, the rhBMP-2 was placed with use of
      the collagen sponge carrier. The autogenous graft most frequently used at present
      for regeneration of the osseous defects of maxillary clefts is iliac crest
      particulate cancellous bone. As a control graft on the contralateral side,
      therefore, autogenous particulate bone and marrow was placed. At the end of 3
      months, the cleft side receiving the BMP-2 showed complete osseous restoration of
      the simulated cleft. The autogenously grafted side exhibited bone repair but
      incomplete regeneration of the bone defect at the early (3-months postoperative)
      stage of healing. CONCLUSIONS AND CLINICAL RELEVANCE: The results of these three
      subhuman primate defect studies--(a) mandibular resection defects in middle-aged
      Macaca fascicularis animals, (b) mandibular resection defects in Macaca
      fascicularis animals over 20 years of age, and (c) simulated bilateral clefts in
      Macaca mulatta animals 1 1/2 years of age (comparable with a 5-year-old child)-
      were very encouraging. Histomorphometric analysis in all of these investigations
      indicated that the use of rhBMP-2 in bone repair without the use of bone grafting
      materials will offer a new method of osseous reconstruction in clinical facial
      bone defects.

PMID- 11314793
TI  - Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial
      nonunions.
AB  - BACKGROUND: The role of bone morphogenetic proteins (BMPs) in osseous repair has
      been demonstrated in numerous animal models. Recombinant human osteogenic protein
      1 (rhOP-1 or BMP-7) has now been produced and was evaluated in a clinical trial
      conducted under a Food and Drug Administration approved Investigational Device
      Exemption to establish both the safety and efficacy of this BMP in the treatment
      of tibial nonunions. The study also compared the clinical and radiographic
      results with this osteogenic molecule and those achieved with fresh autogenous
      bone. MATERIALS AND METHODS: One hundred and twenty-two patients (with 124 tibial
      nonunions) were enrolled in a controlled, prospective, randomized, partially
      blinded, multi-center clinical trial between February, 1992, and August, 1996,
      and were followed at frequent intervals over 24 months. Each patient was treated
      by insertion of an intramedullary rod, accompanied by rhOP-1 in a type I collagen
      carrier or by fresh bone autograft. Assessment criteria included the severity of
      pain at the fracture site, the ability to walk with full weight-bearing, the need
      for surgical re-treatment of the nonunion during the course of this study, plain
      radiographic evaluation of healing, and physician satisfaction with the clinical
      course. In addition, adverse events were recorded, and sera were screened for
      antibodies to OP-1 and type-I collagen at each outpatient visit. RESULTS: At 9
      months following the operative procedures (the primary end-point of this study),
      81% of the OP-1-treated nonunions (n = 63) and 85% of those receiving autogenous
      bone (n = 61) were judged by clinical criteria to have been treated successfully
      (p = 0.524). By radiographic criteria, at this same time point, 75% of those in
      the OP-1-treated group and 84% of the autograft-treated patients had healed
      fractures (p = 0.218). These clinical results continued at similar levels of
      success throughout 2 years of observation, and there was no statistically
      significant difference in outcome between the two groups of patients at this
      point (p = 0.939). All patients experienced adverse events. Forty-four percent of
      patients in each treatment group had serious events, none of which were related
      to their bone grafts. More than 20% of patients treated with autografts had
      chronic donor site pain following the procedure. CONCLUSIONS: rhOP-1 (BMP-7),
      implanted with a type I collagen carrier, was a safe and effective treatment for
      tibial nonunions. This molecule provided clinical and radiographic results
      comparable with those achieved with bone autograft, without donor site morbidity.

PMID- 11314794
TI  - Selection of a control group in BMP clinical studies.

PMID- 11314795
TI  - OP-1 clinical studies.

PMID- 11314796
TI  - Clinical application of the BMPs.

PMID- 11314797
TI  - BMPs: why are they not in everyday use?

PMID- 11314798
TI  - Thoughts on clinical trials to evaluate the action and effectiveness of BMPs in
      bone healing.

PMID- 11314799
TI  - The influence of delivery vehicles and their properties on the repair of
      segmental defects and fractures with osteogenic factors.

PMID- 11314800
TI  - TGF-beta1 release from biodegradable polymer microparticles: its effects on
      marrow stromal osteoblast function.
AB  - BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to
      a bone defect may be beneficial for the induction of a bone regeneration cascade.
      The objectives of this work were to assess the feasibility of using biodegradable
      polymer microparticles as carriers for controlled TGF-beta1 delivery and the
      effects of released TGF-beta1 on the proliferation and differentiation of marrow
      stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated
      into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and
      poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum
      albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content
      (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release
      kinetics and the degradation of PLGA were determined in vitro for as long as 28
      days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene
      fumarate) (PPF) substrate. The dose response and biological activity of released
      TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1
      released from PLGA/PEG microparticles on marrow stromal cell proliferation and
      osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF
      beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and
      released in a multiphasic fashion including an initial burst for as long as 28
      days in vitro. Increasing the initial PEG content resulted in a decreased
      cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower
      buffer pH, which led to decreased release rates of both proteins. The degradation
      of PLGA was increased at higher PEG content and significantly accelerated at
      acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed
      a dose response to TGF-beta1 released from the microparticles similar to that of
      added TGF-beta1, indicating that the activity of TGF-beta1 was retained during
      microparticle fabrication and after growth factor release. At an optimal TGF
      beta1 dosage of 1.0 ng/ml after 3 days, the released TGF-beta1 enhanced the
      proliferation and osteoblastic differentiation of marrow stromal cells over 21
      days of culture, with increased total cell number, alkaline phosphatase activity,
      and osteocalcin production. CONCLUSIONS: PLGA/PEG blend microparticles can serve
      as delivery vehicles for controlled release of TGF-beta1, and the released growth
      factor enhances marrow stromal cell proliferation and osteoblastic
      differentiation in vitro. CLINICAL RELEVANCE: Controlled release of TGF-beta1
      from PLGA/PEG microparticles is representative of emerging tissue engineering
      technologies that may modulate cellular responses to encourage bone regeneration
      at a skeletal defect site.

PMID- 11314801
TI  - Biodegradable poly-D,L-lactic acid-polyethylene glycol block copolymers as a BMP
      delivery system for inducing bone.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs) are biologically active molecules
      capable of eliciting new bone formation. In combination with biomaterials, these
      proteins can be used in a clinical setting as bone-graft substitutes to promote
      bone repair. Collagen from animal sources has previously been the preferred
      carrier material in animal experiments. More recently, synthetic biodegradable
      polymers have been tested as a delivery vehicle for osteoinductive agents. In
      earlier studies performed in our laboratory, it was found that the polylactic
      acid homopolymers (PLA650) and poly-D,L-lactic acid-polyethylene glycol block
      copolymers (PLA650-PEG200) are viscous liquids that can be used as BMP delivery
      systems. METHODS: To obtain new PLA-PEG polymers that exhibit greater plasticity,
      the molecular sizes of PLA and PEG segments in the copolymer chains were
      increased. Plastic PLA-PEG polymers with various molecular sizes and PLA/PEG
      ratios were synthesized, mixed with recombinant human (rh) BMP-2, and implanted
      into the dorsal muscles of mice for 3 weeks to evaluate their capacity to elicit
      new bone formation. To compare the plastic PLA-PEG polymer with the liquid PLA650
      PEG200 polymer, these two polymers were combined with rhBMP-2, implanted, and
      harvested after 3 weeks. Bone mineral content (BMC), bone area, and bone mineral
      density (BMD) of the ectopic new bone were measured by means of single energy X
      ray absorptiometry (SXA). RESULTS: All of the PLA6,500-PEG3,000 implants with 10
      or 20 microg of rhBMP-2 showed new bone formation. In contrast, little or no bone
      formation was seen in other plastic PLA-PEG implants with rhBMP-2. Control
      implants that lacked rhBMP-2 did not show new bone formation. Radiographic and
      histologic examinations showed that the PLA6,500-PEG3,000 implants with rhBMP-2
      harvested 3 weeks after implantation had normal bone characteristics with
      hematopoietic marrow and osseous trabeculae. SXA analysis showed that the values
      for bone mineral content (BMC), bone area, and bone mineral density (BMD) of new
      bone resulting from the use of plastic PLA6,500-PEG3,000 polymers with rhBMP-2
      were significantly higher than those obtained with the liquid PLA650-PEG200
      polymers (p < 0.001 for each of the three values). CONCLUSIONS: These results
      indicate that the PLA6,500-PEG3000 block copolymer with plastic properties works
      effectively as a BMP delivery system. These data suggest that the total molecular
      size and ratio of PLA size to PEG size is an essential factor in determining the
      efficacy of a BMP delivery system. After implantation, it is possible that the
      PLA6,500-PEG3,000 pellets might have absorbed tissue fluids and become swollen,
      resulting in bone formation that exceeded the size of the original implants. This
      expansion characteristic is a potentially beneficial property, given the intended
      practical application of the polymer in the repair of bone defects. CLINICAL
      RELEVANCE: New synthetic biodegradable delivery systems will play an important
      role in the clinical applications of rhBMPs in which local formation of bone via
      an osteoinductive graft material is needed. Further pre-clinical and clinical
      work is necessary to establish the safety of these implants before they are
      adopted for widespread clinical use.

PMID- 11314802
TI  - In vitro and in vivo studies of a bone morphogenetic protein-2 expressing
      adenoviral vector.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs) play important roles in the
      migration of osteoblast progenitor cells, the proliferation of mesenchymal cells,
      and their differentiation into chondrogenic and osteogenic cells. However, the
      optimum procedure to deliver BMPs remains unknown. To examine the effectiveness
      of a gene transfer procedure for the delivery of BMP-2, we constructed a human
      BMP-2-expressing replication-deficient adenoviral vector, AxCAOBMP-2, and
      evaluated its osteoinductive activity in vitro and in vivo. METHODS: C2C12
      myoblasts were infected in vitro with this viral vector or an Escherichia coli
      LacZ gene-expressing control adenovirus vector (AxCALacZ). Twenty-four hours
      after the infection, indirect immunofluorescence was performed. On day 5 after
      the infection, alkaline phosphatase (ALP) in the cells and osteocalcin in the
      culture medium were measured. Furthermore, to examine the effectiveness of gene
      transfer of BMP-2 in vivo, we evaluated osteoinduction by AxCAOBMP-2, under
      transient immunosuppression with cyclophosphamide, given at a dose of 125 mg/kg
      intraperitoneally the day before injection of the adenoviral vector. Twenty-five
      microliters of AxCAOBMP-2 (8.75 x 10(8) plaque-forming units [pfu], Group I) and
      AxCALacZ (1.75 x 10(8) pfu, control group) and 5 microl of AxCAOBMP-2 (1.75 x
      10(8) pfu, Group II) were injected into a right calf muscle of Wistar rats. On
      day 21, bone formation in each group was investigated radiologically and
      histologically. RESULTS: Abundant BMP-2 expression in C2C12 cells infected with
      this viral vector was confirmed by immunofluorescence. C2C12 cells transferred
      with the BMP-2 gene by this vector produced ALP in the cells and also produced
      and secreted osteocalcin in the culture medium. Osteoinduction was found only in
      the AxCAOBMP-2 treated groups with immunosuppression. Osteoinduction activity was
      higher in Group I than in Group II. CONCLUSION: This study demonstrated the
      osteoinductive activity in vitro and in vivo by an adenoviral vector carrying the
      BMP-2 gene. CLINICAL RELEVANCE: Gene therapy with AxCAOBMP-2 under transient
      immunosuppression may be useful for bone reconstruction.

PMID- 11314803
TI  - Artificial articular cartilage: developments and challenges.

PMID- 11314804
TI  - Hepatitis C virus infection in dialysis: an emerging clinical reality.

PMID- 11314805
TI  - Role of platelet surface receptor abnormalities in the bleeding and thrombotic
      diathesis of uremic patients on hemodialysis and peritoneal dialysis.
AB  - BACKGROUND: Patients with chronic renal failure suffer from bleeding diathesis
      and a tendency to accelerated atherosclerosis. Altered platelet function plays a
      well defined role in the hemorrhagic complications of these patients and has a
      probable impact on atherothrombotic disease in uremia. In this study we
      investigated the expression of platelet surface receptors, the glycoprotein GPIb
      (receptor for von Willebrand Factor(vWF) and GPIIb/IIIa (receptor for fibrinogen)
      in patient with chronic renal failure in pre-dialysis status, under hemodialysis
      and peritoneal dialysis treatment, in order to assess the impact of the abnormal
      receptorial status of uremic platelets on the clinical manifestations of
      hemostatic alterations in uremic patients. METHODS: Thirty-seven normal healthy
      subjects (controls = Group A), 18 patients with mild chronic renal failure
      (creatinine = 1.8 +/- 0.5 mg% - Group B), 15 patients with advanced renal failure
      (creatinine = 5.4 +/- 2. 1 mg% - Group C), 18 hemodialysis patients (Group D) and
      11 peritoneal dialysis patients (Group E) were included in the study. The
      expression of platelet surface receptors GPIb and GPIIb/IIIa was investigated
      with monoclonal antibodies CD42 and CD41 (Immunotech, Marseille, France) and a
      FACScan flowcytometer (Becton-Dickinson, USA). RESULTS: Mean values of GPIb
      glycoprotein (mean flow +/- SD) were: group A = 48.14 +/- 9.31; group B = 40.48
      +/- 8.18 (p < 0.005); group C = 34.05 +/- 7.55 (p < 0.0005) versus group A; p =
      0.025 versus group B); group D = 34.51 +/- 7.22 (p < 0.0005 versus group A; p =
      0.025 group B and p = ns versus group C); group E = 26.34 +/- 4.06 (p < 0.0005
      versus group A, p < 0.0005 versus group B, p < 0.005 versus groups C and D). Mean
      values of glycoprotein GPIIb/IIIa were: group A = 375.32 +/- 90.58; group B =
      398.48 +/- 54.26 (p = ns); group C = 426.86 +/- 52.78 (p < 0.025 versus group A;
      p = ns versus group B); group D = 425.17 +/- 75.03 (p < 0.025 versus group A; p =
      ns versus groups B and C); group E = 336.39 +/- 43.26 (p = ns versus group A; p <
      0.005 versus group B, p < 0.0005 versus group C and p < 0.001 versus group D).
      CONCLUSIONS: Our data confirm the receptorial defect of glycoprotein GPIb (the
      receptor for vWF) on the surface of uremic platelets: a negative correlation
      between serum creatinine and the expression of glycoprotein GPIb was found. The
      defect was not corrected by hemodialysis and/or peritoneal dialysis. Hemodialysis
      and peritoneal dialysis have a different impact on the expression of GPIIb/IIIa
      glycoprotein (the receptor for vWF): peritoneal dialysis seems to have a more
      favourable effect by restoring normal values of the expression of this membrane
      integrine. Theoretically the data could be correlated to the better
      biocompatibility of the peritoneal dialysis and to more favorable clinical
      behaviour in terms of accelerated atherosclerosis and athero-thrombotic
      complications in the uremic patients with end stage renal disease. Finally the
      abnormalities of platelet surface receptors may play a main role in the
      hemostatic alterations of uremic patients.

PMID- 11314806
TI  - Electrical current leakage during hemodialysis may increase blood-membrane
      interaction.
AB  - During hemodialysis blood - membrane interaction causes complement activation.
      During dialysis there may be an electrical current leakage to the dialyzer,
      especially if there is a broken ground or a defect in another electrical device
      coupled to the patient. This study investigated whether an electric current of
      1.5 mA DC could alter blood membrane interaction as measured by changes in C3d in
      the blood. Such a high current leakage could occur because there is no protection
      in the dialysis machine (Class 1B) against auxiliary current leakage. Such a
      current could come from a defective external device in contact with the patient
      during hemodialysis. MATERIALS: A dialysis machine (Fresenius 2008C) with a
      filled blood-line system containing about 350 ml whole blood from each of 8
      different donors was used in vitro. Each of the eight test-runs also contained
      1000 U added heparin. The dialysis procedure was performed using hemophan
      membranes (GFS + 12, Gambro) with bicarbonate and potassium 3.0 (D210, Gambro) as
      dialysate. Two electric poles were placed in the blood line, before and after the
      dialyzer (connected in parallel) and the ground was placed at entry and exit of
      the dialysate fluid coming from the machine to the dialysis filter. C3d was
      measured before the start of "dialysis" and at 15, 30, 45 and 60 min, during
      dialysis. Thereafter the 1.5 mA current was switched on and additional samples
      were drawn at 75 and 90 min. The mean C3d values were calculated. Paired non
      parametric statistical analyses were performed. RESULTS: There was a significant
      and continuous increase in C3d as compared to the "predialysis" level. The
      increase during 0 to 30 minutes was greater than that from 30 to 60 minutes
      (p=0.018); the increase in C3d during 60 to 90 min, was greater than that from 30
      to 60 min (p=0.018) and there was no difference between the 0 to 30 and the 60 to
      90 min increases. CONCLUSIONS: A current, used in this study, was able to induce
      a blood membrane interaction during in vitro dialysis. Even a weaker current
      leakage might have such adverse effects and similar interactions seem possible
      during regular dialysis depending on the extent of the leakage.

PMID- 11314807
TI  - A semi-automatic algorithm for reducing the time spent on routine follow-up of
      cardioverter defibrillators.
AB  - BACKGROUND: The routine follow-up of cardioverter defibrillators (CD) is a time
      consuming procedure. AIM of the STUDY and METHODS: The present study was a
      prospective randomized cross-over evaluation on the clinical usefulness of a
      specific semi-automatic software algorithm (Quick Check) for CD follow-up,
      available in CPI Guidant systems (CD and programmer). Time-saving, while ensuring
      all the required data and patient safety, was evaluated in a large group of
      patients (105), recruited in different centers. In the same session and under a
      physician's supervision all patients underwent a follow-up with the aid of Quick
      Check or a standard follow-up, in a randomized sequence. Each patient served as
      his own control. RESULTS: In the overall population of 105 patients, the time
      spent for follow-up was reduced by Quick Check from 186+/-105 sec to 106+/-67 sec
      (p<0.0001) (43% reduction). The reduction in time spent for follow-up with Quick
      Check was the same (43% reduction) in patients with detected episodes (n=38)
      (from 241+/-144 sec to 138+/-95 sec (p<0.0001)) and in patients without detected
      episodes (n=67) (from 154+/-52 sec to 88+/-34 sec (p<0. 0001)). No adverse events
      or deletion of potentially useful data was detected by the supervising physician.
      CONCLUSIONS: Use of a specific software algorithm for routine follow-up of
      implanted CDs allows a significant shortening of the time spent on routine follow
      up, thus reducing costs. The supervision of a physician is a guarantee of patient
      safety.

PMID- 11314808
TI  - Estimation of wall shear stress in bypass grafts with computational fluid
      dynamics method.
AB  - Coronary artery bypass graft (CABG) operation for coronary artery disease with
      different types of grafts has a large clinical application world wide.
      Immediately after this operation patients are usually relieved of their chest
      pain and have improved cardiac function. However, after a while, these bypass
      grafts may fail due to for example, neointimal hyperplasia or thrombosis. One of
      the causes for this bypass graft failure is assumed to be the blood flow with low
      wall shear stress. The aim of this research is to estimate the wall shear stress
      in a graft and thus to locate areas were wall shear stress is low. This was done
      with the help of a blood flow computer model. Post-operative biplane angiograms
      of the graft were recorded, and from these the three-dimensional geometry of the
      graft was reconstructed and imported into the computational fluid dynamics (CFD)
      program FLUENT. The stationary diastolic flow through the grafts was calculated,
      and the wall shear stress distribution was estimated. This procedure was carried
      out for one native vessel and two different types of bypass grafts. One bypass
      graft was a saphenous vein and the other one was a varicose saphenous vein
      encased in a fine, flexible metal mesh. The mesh was attached to give the graft a
      defined diameter. The computational results show that each graft has distinct
      areas of low wall shear stress. The graft with the metal mesh has an area of low
      wall shear stress (< 1 Pa, stationary flow), which is four times smaller than the
      respective areas in the other graft and in the native vessel. This is thought to
      be caused by the smaller and more uniform diameter of the metal mesh-reinforced
      graft.

PMID- 11314809
TI  - Cardiomyoplasty: long-term results in ischemic cardiomyopathy.
AB  - INTRODUCTION: Cardiomyoplasty was introduced into clinical practice in 1985 by
      Alain Carpentier. Since then, the procedure has been performed on more than 400
      patients worldwide. The latissimus dorsi muscle is prepared maintaining the
      vascular supply, then the muscle flap is wrapped around the heart and connected
      to a cardiomyostimulator. The muscle is later stimulated synchronously with
      ventricular systole to augment the cardiac contractility. METHODS: To evaluate
      the long-term outcome of cardiomyoplasty, we investigated 3 patients electively
      undergoing this procedure in our hospital. All of these patients (2 male, 1
      female) had severe chronic heart failure which did not respond to optimal medical
      treatment. The mean follow-up time was 42 months (range 24 - 60). All patients
      showed symptoms corresponding to NYHA class III, and one patient intermittently
      showed class IV despite conventional medical therapy. Patients were evaluated at
      6-month intervals for 2 years with right heart catheterization, radionuclide
      scans, echocardiography, as well as questionnaires for assessing quality of life.
      RESULTS: There was no operative mortality. One patient experienced sudden death 2
      years after operation. There were no significant changes in hemodynamic variables
      at 6, 12 or 24 months after surgery, respectively. Left ventricular ejection
      fraction increased from 20.0 ( 9.2 to 40.0 +/- 7.1 % (p = 0.05) 1 year after
      operation. Considerable improvement of symptoms was seen in all, and 1 patient
      returned to work. NYHA-class decreased from 3.1 to 2.0 (p = 0.02). CONCLUSIONS:
      Following cardiomyoplasty, patients may exhibit impressive clinical improvement
      with less striking changes of objective hemodynamic parameters. Thus, in our
      patients, dynamic cardiomyoplasty improves quality of life. We do not consider
      this treatment to be an alternative to heart transplantation. It does, however,
      provide a therapeutic option for patients for whom transplantation is
      contraindicated.

PMID- 11314810
TI  - Teletransmission system supporting intensive insulin treatment of out-clinic type
      1 diabetic pregnant women. Technical assessment during 3 years' application.
AB  - A telematic system supporting intensive insulin treatment of pregnant type 1
      diabetic out-clinic patients was implemented and technical efficiency of the
      system was evaluated over long-term ambulatory application. The system consists
      of a patient teletransmission module (PTM) and a central clinical control unit
      (CCU). The PTM contains a one-box blood glucose meter and electronic logbook, a
      modem and a dial-up or cellular phone set. The CCU consists of a PC computer with
      a modem and DIAPRET - an original program designed to monitor the intensive
      insulin treatment. The system was installed in the Clinic of Gastroenterology and
      Metabolic Disease, MA Warsaw and was tested for 166 +/- 24 days on 15 pregnant
      type 1 diabetic women. Telemonitoring of the patient data was done automatically.
      No major technical problems with proper operation or handling of the system was
      noted. Total effectiveness was 69.3 +/- 13.0% and technical effectiveness 91.5 +/
      6.1%. The efficacy of the system was not significantly influenced by patient
      intelligence level, education level or place of residence (p < 0.05). Significant
      improvement of metabolic control was noted during application of the system. In
      conclusion, the telematic system we developed and implemented should have a
      positive influence on the quality of diabetes treatment during pregnancy.

PMID- 11314811
TI  - Cascade filtration (CF) with the Haemonetics MCS+: a new technical adaptation.
AB  - CF was introduced in clinical medicine in 1980. Up to now, exclusively two-vein
      procedures have been carried out with some limitations to expansion of this
      technique. In this report we describe the very first application of single-needle
      CF carried out with Haemonetics MCS + apparatus. Twenty procedures were completed
      without any untoward effect in patients suffering from TTP, post-hepatitic
      cryoblobulinemia, familial hypercholesterolemia and acute Guillan-Barre Syndrome.
      From 1 to 4 sessions were carried out per patient with the expected laboratory
      and clinical results. The only limit is the procedure time that averages 231 +/-
      48 min., approximately 40% longer than two needle procedures.

PMID- 11314812
TI  - Blood flow distribution in a polymyxin coated fibrous bed for endotoxin removal.
      Effect of a new blood path design.
AB  - The analysis of flow distribution in cartridges designed for hemoperfusion is
      extremely important. Taking advantage of a new imaging technique, based on the
      analysis of a helical scanner-generated imaging sequence, we studied the blood
      flow distribution in a series of cartridges for extracorporeal removal of
      endotoxin. Cartridges with improved design were compared to cartridges with a
      standard design. The improved design consists in a different structure of the
      holes of the distributor of the flow within the adsorbent unit. Cartridges were
      studied in vitro with human blood from voluntary donors at blood flows of 100 and
      250 ml/min. The progression of density in specific regions of interest (ROI) was
      analyzed to detect the distribution of the dye injected in the blood circuit. The
      study demonstrates that both at 100 ml/min and at 250 ml/min of blood flow, the
      progression of flow appears more homogeneous in the devices with improved design.
      In detail, the flow distribution measured by the incremental density values
      detected in the ROIs of the proximal comers (close to the arterial port) and in
      the ROIs of the central region of the device (close to the inner wall of the
      case) displays a significant difference between the standard and the improved
      device. The ROIs studied in the standard devices display a slower increase in
      density and significantly lower absolute values expressed in Hounsfield units.
      The experimental method utilized to analyze flow distribution seems to represent
      an important means to study the performance and design of this type of device.

PMID- 11314813
TI  - A new blood donation strategy: automated blood collection (ABC).
AB  - BACKGROUND: The aim of this study was to find out if Cobe Trima, a blood cell
      separator that automatically collects RBC, PLT and plasma, is adequate for
      routine multiple blood donation by apheresis. MATERIALS AND METHODS: Eighty
      donors underwent multiple blood component donations by Cobe Trima. Blood counts
      were determined on the apheresis products to analyze their quality. RESULTS:
      Eighty procedures were performed collecting 193 products. The average platelet
      yield was 3.5x10(11) (+/- 0.46) in the 54 single product (SP) procedures and
      7x10(11) (+/- 0.88) in the 26 double product (DP) procedures. WBC contamination
      of the PLT products was 1.7 x 10(5) (1.2-4.2). The mean platelet efficiency was
      60 +/- 8.35% for SP and 66 +/- 9.59% for DP. The hemoglobin (Hb) content per unit
      was 46.21 g (+/- 7.84) in 8 DP and 40.82 g (+/- 6.41) in 34 SP procedures.
      CONCLUSION: The production of standardized blood components with good PLT yield
      and low WBC contamination plus high efficiency makes Trima one of the best blood
      cell separators of the new generation.

PMID- 11314814
TI  - Towards an international triage scale.

PMID- 11314815
TI  - Hantavirus infections: clinical presentation in the emergency room.
AB  - We present a retrospective review of Hantavirus infection in the emergency
      department. Thirteen cases of Hantavirus infections with renal syndrome from July
      1989 to August 1999 were analysed. The diagnosis was confirmed by detection of
      Hantavirus antibodies in all cases. Fever, chills and headaches were universally
      present. Intense back pain was associated in 77% of the patients.
      Thrombocytopenia, abnormal urinalysis, hypertransaminasaemia, increased lactate
      dehydrogenase were the principal biological patterns. All these parameters
      returned to their normal level, and all the patients recovered a normal renal
      function without sequels. The management is supportive. Only one patient in our
      series had to be dialysed. Hantavirus disease should be included in the
      differential diagnosis of acute renal failure with thrombocytopenia, particularly
      in patients with suspected exposure in known endemic areas. The differential
      diagnosis of any perplexing case of undifferentiated febrile illness with acute
      renal failure and thrombocytopenia should include Hantavirus infection.

PMID- 11314816
TI  - Non-invasive positive pressure ventilation for exacerbation of chronic
      obstructive pulmonary patients in the emergency department.
AB  - Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD)
      commonly present to the emergency department for treatment. Some of them, despite
      appropriate therapy become more dyspnoeic with increasing acute respiratory
      failure. The requirement for intubation and mechanical ventilation is for these
      patients often associated with a prolonged and complicated intensive care unit
      stay and has been associated with morbidity and mortality rates in excess. Non
      invasive ventilation (NIV) emerged recently as a means of reducing those
      complications. NIV can be a safe and effective means of augmenting ventilation
      and decreasing inspiratory work in many patients with acute exacerbation of COPD.
      NIV is generally started in the intensive care unit. Except for a few negative
      studies, the overall compending studies seem to be in favour of the utilization
      of NIV in cases of exacerbation of COPD patients. There are few published data on
      the question whether NIV could or should be started earlier and initiated in the
      emergency department. It seems that NIV treatment could be an effective addition
      to standard treatment especially for acute exacerbation of COPD. A more extensive
      and routine use of non-invasive ventilation in the emergency department requires
      further study.

PMID- 11314817
TI  - Biphasic-flow induced ventilation allows simultaneous ventilation in several
      animals, using a single multiple output ventilator--a preliminary report.
AB  - Biphasic-flow induced ventilation (BiFIV) is a variable time-cycled tracheal gas
      insufflation mode, using a specific multiluminal endotracheal tube. Some recent
      studies have reported efficiency of this new ventilatory mode in experimental in
      vitro and in vivo settings. We hypothesized that this ventilatory mode could be
      able to deliver simultaneous efficient ventilation for several animals, using a
      single ventilator prototype. The study was performed in three groups of three
      domestic pigs with a normal lung compliance. Each pig was initially
      anaesthetized, intubated with the specific endotracheal tube, and ventilated with
      a conventional ventilatory device. The animals were then simultaneously
      ventilated under BiFIV, using a single ventilator prototype, for each group of
      three animals. Physiological parameters and arterial blood gases were recorded at
      each study phase. All animals but one survived the experiment. We did not observe
      any significant differences in arterial gas exchange, under both ventilatory
      modes. Oxygenation was as efficient for each three animals ventilated under
      BiFIV, using a single ventilator device, as under conventional ventilation, using
      three separate ventilators (PaO2 = 112+/-17 mmHg under conventional ventilation
      versus 115+/-16 mmHg under BiFIV). In conclusion, variable time-cycled tracheal
      gas insufflation may allow an efficient multiple ventilation on several animals,
      using a single multiple output ventilatory device, in a normal lung animal model.
      If validated on subsequent pathological models, it could thus be interesting in
      laboratory and/or mass casualty situations.

PMID- 11314818
TI  - Systematic triage in the emergency department using the Australian National
      Triage Scale: a pilot project.
AB  - The objective of this study was to evaluate the validity in Belgium of the
      National Triage Scale for judgement of the urgency of a patient's condition and
      making a case-mix description of the patient profiles in the different urgency
      categories. The study is of a descriptive retrospective and descriptive
      correlational design and was carried out in the emergency department at the
      University Hospital Gasthuisberg in Leuven, Belgium. The urgency of patients
      arriving at the emergency department was evaluated during one randomly selected
      shift a day over 12 weeks in 1997 by one of the four triage-educated nurses,
      using an instrument based on the National Triage Scale. Patient identification
      and outcome parameters were retrieved from the existing computer system. The data
      were mainly analysed using the Ridit analysis. Overall 3650 patients were
      evaluated: Category 1, 4.19%; Category 2, 24.44%; Category 3, 39.32%; Category 4,
      27.97%; Category 5, 4.08%. Any similarity between sentinel diagnoses as well as
      between the admission percentages in this pilot study and the reference from
      Australia (Z = 0.827; p > 0.05) was noted. Different aspects influenced the
      triage nurses while determining the degree of urgency. Urgency categories
      profiles revealed a significant effect of age (Kruskall-Wallis = 530.5; p =
      0.000). Higher categories of urgency resulted in a higher degree of admission (t
      (df = 3640) = 643.45; p = 0.000). It is concluded that a resemblance between the
      pilot study and the reference confirms the predictive validity of the scale used.
      Patient profiles in the different urgency categories give a description of the
      emergency department population.

PMID- 11314819
TI  - Indications of Philadelphia collar in the treatment of upper cervical injuries.
AB  - The principles of the management of upper cervical injuries remain controversial.
      The specific anatomical conditions render upper cervical injuries more
      problematic than lower cervical injuries. Here we present and discuss our
      experiences with upper cervical injury, comparing them with other treatment
      modalities. The 24 patients admitted to our department with upper cervical injury
      were treated surgically or conservatively according to their neurological and
      radiological status. Five patients were treated surgically due to neurological
      abnormality associated with compression to neural structures observed in
      computerized tomography/magnetic resonance imaging (CT/MRI). Patients with no
      neural compression were managed conservatively, with the Philadelphia collar. All
      patients showed stable fracture healing and experienced no additional clinical
      disability on follow-up after a minimum of 3 months, except one who died due to
      cardiac and respiratory failure. Regardless of the type of injury, indication for
      surgery in many cases of upper cervical injury is neurological abnormality
      associated with radiologically observed neural compression. It is our belief
      that, in the absence of both neurological abnormality and compression to neural
      structures observed in CT/MRI, treatment with the Philadelphia collar alone is
      safe, cost-effective and easily applicable for many cases of upper cervical
      injury.

PMID- 11314820
TI  - Traumatic rupture of the thoracic aorta: time to diagnosis and treatment.
AB  - Survival of patients with traumatic rupture of the thoracic aorta (TRTA) depends
      on early surgical repair. Six cases of TRTA were treated at our institution in 7
      years. Time to diagnosis was 1.5, 3, 4, 36, 91 and 140 hours (mean = 46 hours).
      Diagnosis was made by computed tomography in one and by angiography in five
      cases. Time from arrival to treatment was 3, 9, 5, 46, 117 and 152 hours (mean =
      55 hours). All six patients were treated by clamp and suture technique, with a
      mean cross clamp time of 48 minutes. Significant delay in diagnosis and treatment
      occurred in three patients. The reasons for delay were unrecognized signs for
      TRTA on the initial chest X-ray, a false-negative result of transoesophageal
      echography and not considering the diagnosis of TRTA. The diagnosis of TRTA
      requires a high index of suspicion and should always be considered in victims of
      high impact trauma.

PMID- 11314821
TI  - Ambulance times of Ankara emergency aid and rescue services' ambulance system.
AB  - The aim of this study was to determine various times related to the ambulance
      activities of Ankara Emergency Aid and Rescue Services (EARS) and if necessary
      contribute to the improvement of them. A descriptive study was planned to
      determine various times related to the ambulance activities of Ankara EARS. The
      data was collected by one of the researchers. The study was conducted between 1
      October 1995 and 30 September 1996. The variables of the study were: delay time,
      response time, time at the scene (scene time), round trip time, transport time
      and total run time of Ankara EARS ambulance activities. Ankara EARS Emergency
      Call Registry Forms (5638 forms) were evaluated for the above stated variables.
      The computer program EPI-INFO 5.0 was used in the study. The median response time
      of Ankara EARS was found to be 9 minutes. In the research year, the median delay
      time was 2 minutes. Median arrival to patient contact time of Ankara EARS was 2
      minutes. Median time at the scene was 7 minutes. Median round trip time of the
      system was 44 minutes. The median time to arrive at the scene from the ambulance
      station was 8 minutes. The median transport time was 10 minutes. The median total
      run time was 30 minutes. As the median response time was found to be 9 minutes it
      is concluded that there should be more ambulance vehicles to improve this time of
      Ankara EARS. Due to financial problems, times were recorded manually by the
      ambulance crew and dispatchers of Ankara EARS. If digital and electronic
      recording systems are used, these times might be more precise.

PMID- 11314822
TI  - Injury caused by deeply penetrating knife blade lodged in infratemporal fossa.
AB  - Knife-inflicted, deeply penetrating head and neck trauma is an uncommon life
      threatening injury and a challenging problem. An examination of the neurovascular
      and systemic physical status is a first requirement and the decision as to which
      approach to adopt for the removal of the blade is of critical importance. Here we
      report a rare case of a pre-auricular stab wound with the knife blade deeply
      lodged in the extracranial infratemporal fossa. Radiological investigations
      showed that the knife blade had entered from the temporomandibular joint and
      become lodged through the anterior margin of foremen magnum below the petrosal
      bone. Minimal left vocal cord paresis, left palatal weakness and a slight
      deviation of the tongue towards the left side were observed. The other
      neurological and systemic physical evaluations were normal. Simple withdrawal of
      the blade in the operating room did not cause serious neurovascular injury. Here
      we discuss and compare the expanded exposure of anatomical structures for blade
      removal and simple withdrawal in similar injuries.

PMID- 11314823
TI  - Stab wound to the neck--a rare presentation.

PMID- 11314824
TI  - Hyperosmolar diabetic non-ketotic coma, hyperkalaemia and an unusual near death
      experience.
AB  - Generally, cardiac arrest due to pulseless electrical activity has a poor
      outcome, except when reversible factors such as acute hyperkalaemia are
      identified and managed early. Hyperosmolar diabetic non-ketotic coma may lead to
      acute hyperkalaemia. Hyperosmolar diabetic non-ketotic coma is a metabolic
      emergency usually seen in elderly non-insulin dependent diabetics, characterized
      by severe hyperglycaemia, volume depletion, altered consciousness, confusion and
      less frequently neurological deficit. Cerebrovascular accident or transient
      ischaemic attack may be mistakenly diagnosed, particularly if the patient has no
      history of diabetes mellitus. Delays in diagnosis and management of glycaemic
      emergencies presenting as a constellation of neurological abnormalities can be
      avoided by routine early measurement of blood glucose. Hyperosmolar diabetic non
      ketotic coma should be considered in any patient with altered consciousness or
      neurologic deficit in conjunction with hyperglycaemia. As hyperosmolar diabetic
      non-ketotic coma results in severe fluid depletion, electrolyte disturbance,
      profound hyperglycaemia and an altered mental state, the guiding principles of
      therapy include aggressive rehydration, insulin therapy, correction of
      electrolyte abnormalities and treatment of any underlying illnesses. Treatment of
      acute hyperkalaemia includes calcium ions, insulin with dextrose, salbutamol and
      haemodialysis.

PMID- 11314825
TI  - Acute calcifying tendonitis--an unusual cause of carpal tunnel syndrome.
AB  - We report a rare case of acute calcifying tendinitis resulting in acute carpal
      tunnel syndrome. Acute medical staff should be aware of this condition and the
      importance of early referral to avoid long term median nerve neuropathy.

PMID- 11314827
TI  - Anaesthetic problem registers.

PMID- 11314826
TI  - Intravenous magnesium is ineffective in adult asthma, a randomized trial.
AB  - Intravenous magnesium sulphate (MgSO4) has been tried in the emergency department
      treatment of asthma since the mid-1980s, but published reports vary as to its
      efficacy. The literature suggests that it may be effective in the more severely
      ill asthmatic. We evaluated i.v. MgSO4 in adult asthmatics having a moderate to
      severe exacerbation. The study was performed in a convenience sample of adult
      asthmatics between the ages of 18 and 55 presenting to the emergency department
      with a peak expiratory flow (PEF) of < 100 l/min or < 25% of predicted flow.
      Patients received either 2.0 grams of MgSO4 or placebo in a randomized, double
      blind fashion. All patients received inhaled bronchodilators and i.v. steroids.
      Outcome variables were: improvement in PEF, subjective respiratory distress as
      measured by the Borg dyspnoea scale (BDS) and hospital admission. The first
      visits of 42 patients presenting with acute asthma exacerbations were evaluated,
      18 receiving MgSO4 and 24 receiving placebo. The t = 60 peak flow in the MgSO4
      group was 174 l/min versus 212 l/min in placebo, p = 0.04. Controlling for age,
      heart rate, initial PEF and initial BDS in ordinal logistic regression, the t =
      60 Borg scale of subjective dyspnoea had an odds ratio of 1.54 in favour of more
      dyspnoea in MgSO4 (95% C.I., 0.36-6.67; p = 0.56). Five of 18 patients (28%)
      receiving MgSO4 were admitted compared with 5 of 24 (21%) receiving placebo (p =
      0.72). In moderately severe adult asthmatics, 2.0 grams of MgSO4 i.v. resulted in
      less improvement in peak expiratory flow compared with placebo. MgSO4 did not
      appear to decrease subjective dyspnoea or the hospital admission rate. This
      evidence does not support the use of MgSO4 in the treatment of acute asthma.

PMID- 11314828
TI  - A multiple-hospital anaesthetic problem register: establishment of a regionally
      organized system for facilitated reporting of potentially recurring anaesthetic
      related problems.
AB  - A regionally organized system aiming to facilitate reporting and retrieval of
      information about potentially recurring anaesthetic-related problems has been
      established, covering 20 separate hospitals. Components of the system include a
      reporting package to facilitate use by anaesthetists in busy clinical practice;
      centralized clerical support; supervision by anaesthetists; reports and laminated
      cards supplied to the patient; and a permanently accessible database. A new
      classification system for difficulties in airway management has been developed as
      part of the system. After initial establishment, the system has been utilized by
      a broad cross-section of anaesthetists in the region. The first 350 reports are
      described. The reporting rate is approximately 0.3% of all anaesthetics given in
      the region. We believe the success of this system has been primarily due to
      features aiming to facilitate reporting, "local" ownership and supervision by
      clinical anaesthetists.

PMID- 11314829
TI  - Anaesthesia alert: an integrated, networked, register of paediatric anaesthetic
      problems.
AB  - The Paediatric Register of Anaesthetic Problems (PaedRAP) is a network-based
      anaesthesia hazard alert system. It is integrated with pre-anaesthesia
      consultations and patient questionnaires. All files, both electronic and on
      paper, are available 24 hours a day close to the operating theatres. This ensures
      that pertinent information is readily available when and where it is most needed.
      The PaedRAP is also linked to the automated theatre booking system to print
      warnings on the theatre lists. This minimizes the chance that important
      information goes unnoticed. Documentation of the progression of the various
      categories of patient problems and evolving management strategies has been useful
      both for individuals and groups.

PMID- 11314830
TI  - The cerebral and systemic kinetics of thiopentone and propofol in halothane
      anaesthetized sheep.
AB  - The cerebral and systemic kinetics of intravenous thiopentone (250 mg over 2
      minutes, n=5) and propofol (100 mg over 2 minutes, n=6) were determined in sheep
      anaesthetized with halothane (2.0%) and mechanically ventilated to an end-expired
      carbon dioxide tension of 40 mmHg. The sheep were previously instrumented with
      arterial and sagittal sinus (effluent from the brain) blood sampling catheters.
      Systemic kinetics were inferred from the time-course of the arterial blood
      concentrations, and cerebral kinetics from the time-course of the arterio
      sagittal sinus concentration difference across the brain. Under halothane
      anaesthesia, the peak arterial concentrations of each drug occurred at the end of
      the two-minute infusion, and was 42.3 mg/l and 12.3 mg/l for thiopentone and
      propofol, respectively. Propofol had a significantly larger systemic clearance
      (3.19 l/min) than thiopentone (0.99 l/min). The brain concentrations of propofol
      equilibrated more slowly with the arterial concentrations than those of
      thiopentone. The extraction ratio across the brain near the end of the infusions
      (1.5 min) were 0.85 and 0.46 respectively. These data were also compared to
      analogous previously published data for initially conscious sheep. The systemic
      kinetics of thiopentone were little affected by halothane anaesthesia. For
      propofol, halothane anaesthesia was associated with a statistically significant
      reduction in clearance (50% of awake), a slower initial half-life (247% of
      awake), and the emergence of a second slower half-life in some sheep. The
      cerebral kinetics of both drugs were subtly altered by halothane anaesthesia.

PMID- 11314831
TI  - Total intravenous versus inhalational anaesthesia for colonoscopy: a prospective
      study of clinical recovery and psychomotor function.
AB  - A randomized, prospective study was conducted on 69 patients comparing recovery
      after two different anaesthetic techniques for ambulatory colonoscopy. Thirty
      five patients received an intravenous fentanyl (1 microg/kg), midazolam (0.05 to
      0. 075 mg/kg) and propofol (10 to 20 mg boluses as required) combination. 34
      patients received sevoflurane in 67% nitrous oxide. Drug administration was
      titrated to clinical signs. At baseline and 30, 60, 90 and 120 minutes after the
      procedure patient performance on a comprehensive battery of psychomotor tests was
      recorded. Emergence times were noted. Depth of sedation was assessed at 5 minute
      intervals for 30 minutes after the end of the procedure. Emergence times were
      faster in the fentanyl/midazolam/propofol group by 2.2 minutes. A lower sedation
      score was detected at 20 minutes in the sevoflurane/nitrous oxide group.
      Psychomotor impairment was of a greater magnitude and more prolonged by 30 to 90
      minutes in the fentanyl/midazolam/propofol group. It is concluded that a
      sevoflurane/nitrous oxide anaesthetic has a suitable recovery profile for
      ambulatory colonoscopy and results in faster recovery of cognitive function
      compared with a fentanyl, midazolam and propofol combination.

PMID- 11314832
TI  - Co-administration of drugs and blood products.
AB  - The addition of a drug to a blood product intravenous line raises the question of
      physical and chemical compatibility of the drug with the blood and any
      preservatives or additives in the blood product. This clinical scenario is
      encountered frequently, however the practice has not been well studied. Protocols
      at most institutions prohibit the addition of drugs to blood products. We
      investigated the addition of analgesic drugs used for patient-controlled
      analgesia (morphine 1 mg/ml, pethidine 10 mg/ml and ketamine 1 mg/ml) to a
      standard red cell concentrate, resuspended red blood cells. The red cells were
      analysed by a Blood Transfusion Service Haematologist and subjected to standard
      quality control tests. The morphology of the red cells in resuspended red blood
      cell preparations was unchanged by the addition of these drugs at any stage
      during storage. The drug concentration in the resuspended red blood cell serum
      was measured at 0 and at 20 minutes and there was no decrease in concentration
      which showed that there was no loss of free drug in the resuspended red blood
      cell serum. This study demonstrates that the concern regarding injury to red
      cells in standard red cell concentrates by addition of these drugs is
      unjustified.

PMID- 11314833
TI  - A comparative study of three different methods of administering metaraminol
      during spinal anaesthesia in the elderly.
AB  - We compared three methods of administering metaraminol during spinal
      (subarachnoid) anaesthesia. Fifty-two elderly patients with fractured hips were
      studied. Blood pressure was maintained by either intramuscular (i.m.) metaraminol
      (0.1 mg x kg(-1)), intravenous (i.v.) boluses (0.01 mg x kg(-1)) or an infusion
      (0.05 mg x kg(-1) x h(-1)). Non-invasive blood pressure was recorded every one
      minute. Spinal anaesthesia initially decreased the systolic arterial pressure by
      15 (14) % compared to 35 (15) % for diastolic pressure (P<0.001). I.m.
      metaraminol restored the systolic arterial pressure back to baseline values (
      3%), but there was significant between-subject variability resulting in a very
      unpredictable effect. I.v. boluses and infusion had a more predictable effect and
      maintained systolic arterial pressure at about 20% below baseline. Range of
      effect, measured by inter-quartile range and variance, was greatest in the i.m.
      group and least in the infusion group (P<0.003). I.m. metaraminol during spinal
      anaesthesia has a very unpredictable effect. Infusions of metaraminol provided
      the best blood pressure control. Diastolic blood pressure fell significantly
      after spinal anaesthesia and this merits further investigation.

PMID- 11314834
TI  - Tramadol for postoperative shivering: a double-blind comparison with pethidine.
AB  - In most operating and recovery rooms, shivering is controlled by the use of
      humidifiers, warming blankets, and inhalation of humidified heated oxygen.
      However, pharmacological control is an effective alternate treatment modality.
      This randomized, double-blind trial, conducted in 30 ASA Grade 1 or 2 patients,
      was designed to explore the efficacy of tramadol and pethidine in the treatment
      of post-anaesthetic shivering. Tramadol is an inhibitor of the re-uptake of
      serotonin (5-hydroxytryptamine) and norepinephrine in the spinal cord. This
      facilitates 5-hydroxytryptamine release, which influences thermoregulatory
      control. We compared the efficacy of tramadol with that of pethidine, presently a
      widely used drug for the control of shivering. Patients received either tramadol
      1 mg/kg or pethidine 0.5 mg/kg intravenously and the grade of shivering, pulse
      rate, blood pressure and respiratory rate were observed every 10 minutes after
      injection for one hour Shivering was significantly more likely to have ceased in
      the tramadol group (12 of 15 versus 4 of 15 cases, P<0.05) at 10 minutes after
      drug administration and this control was better sustained. No patients receiving
      tramadol had a recurrence of shivering. It is concluded that intravenous tramadol
      1 mg/kg is more effective for the treatment of postoperative shivering than
      pethidine 0.5 mg/kg.

PMID- 11314835
TI  - Adrenocortical response and cortisone replacement in systemic inflammatory
      response syndrome.
AB  - The use of steroids as an adjunct to antimicrobial therapy has been controversial
      for many decades. Recent reports of the use of steroids in supraphysiological
      rather than in "industrial" doses in patients with sustained circulatory
      instability has re-ignited the debate. Anecdotal reports of adrenal insufficiency
      in septic patients have suggested a relative cortisol deficiency in these
      patients with poor survival if not given supplementary steroids. The possibility
      that the hypothalamic pituitary adrenal axis is intimately involved in the
      pathogenesis of this entity has not previously been highlighted. This review
      looks at the relationship of sustained cytokine release and the possibility of
      altering the stress response with progressive loss of adrenocorticotrophic
      hormone release and subsequent diminution in adequate cortisol levels. The
      reliance on, and misinterpretation of, the short synacthen test in diagnosing the
      possibility of this condition is emphasized.

PMID- 11314836
TI  - Glyceryl trinitrate and acute uterine relaxation: a literature review.
AB  - The use of nitro-vasodilators for achieving rapid uterine relaxation in the
      resolution of obstetric emergencies has been documented for nearly 120 years.
      Glyceryltrinitrate (GTN) is the most commonly used nitro-vasodilator for this
      purpose, with the presumed mechanism of action being via nitric oxide and cyclic
      guanosine monophosphate (cGMP) mediated processes. GTN is known to release nitric
      oxide to effect smooth muscle relaxation and some dose response data is available
      for its vasodilator activity. Human myometrium is known to synthesize and respond
      to nitric oxide, with changes in the production of and sensitivity to nitric
      oxide being subject to the cyclical and gestational state of the uterus.
      Experimental data on the efficacy of GTN in reliably producing uterine relaxation
      is conflicting and inconsistent. A total of 32 studies and case reports on the
      use of GTN in achieving rapid uterine relaxation have appeared in the English
      language literature. Case reports are subject to reporting bias and prospective
      randomized controlled trials are not without design flaws. Indications for the
      use of GTN in achieving rapid uterine relaxation cover the antepartum,
      intrapartum and postpartum periods. The safety of GTN during obstetric
      emergencies appears high, with no adverse maternal or neonatal outcomes. To
      establish the efficacy of GTN in reliably achieving uterine relaxation, well
      designed randomized controlled trials in labouring women are required.

PMID- 11314837
TI  - Life-threatening cardiac failure in a healthy young female with Irukandji
      syndrome.
AB  - We present a case of a previously well 24-year-old female patient who developed
      severe and life-threatening Irukandji syndrome that required ventilation and
      inotropic support. This case provides further evidence that there are jellyfish
      other than the Irukandji jellyfish that can cause cardiac decompensation, and
      there is a suggestion that application of a pressure immobilization bandage may
      worsen the envenomation. We include our recommended treatment for the Irukandji
      syndrome.

PMID- 11314838
TI  - Excision of a giant hydatid cyst of the lung under thoracic epidural anaesthesia.
AB  - We present a patient with a large pulmonary hydatid cyst compressing underlying
      lung, with previous pulmonary tuberculosis, who presented in respiratory failure.
      After institution of thoracic epidural anaesthesia employing 0.25% bupivacaine,
      1% lignocaine and fentanyl, the patient was placed in the sitting position and
      the hydatid cyst excised and drained after a limited rib resection. An air leak
      persisted until the 16th postoperative day. A marked improvement in symptoms as
      well as in spirometly and arterial blood gases occurred, and the patient was
      discharged on the 20th day. Thoracic epidural anaesthesia may be a safer method
      than general anaesthesia for removal of a hydatid cyst in a patient with severe
      respiratory compromise.

PMID- 11314839
TI  - Self-inflating ventilation bags.

PMID- 11314840
TI  - A device for the teaching of epidural insertion.

PMID- 11314841
TI  - An intermittent fault involving an Ulco anaesthetic machine.

PMID- 11314842
TI  - Intravenous cannula hub colours.

PMID- 11314843
TI  - Propofol/remifentanil in neurosurgery.

PMID- 11314844
TI  - The history of intravenous anaesthesia: the barbiturates. Part 1.

PMID- 11314845
TI  - 'Patient' voices, social movements and the habitus; how psychiatric survivors
      'speak out'.
AB  - What is the 'voice' of the mental health 'user'? This paper seeks to address this
      question through the presentation of a detailed comparative analysis of two
      anthologies written by people living with mental 'illness' in the 1950s and
      1990s. Using a narrative-style qualitative analysis, the structure and content of
      the two anthologies is explored. The analysis illustrates the way in which the
      'voice' of the mental patient in the 1950s was very different to that of today.
      The paper then aims to provide a theoretical explanation that accounts for this
      transformation of voice. Appropriating theoretical concepts from phenomenology
      and sociology, in particular, Bourdieu's concept of 'habitus', the paper explores
      the way in which the 'personal' voice of the mental patient is formulated in
      dialogical relation to wider public and collective movements. These, in turn,
      connect to broader transformations in the social, economic and health 'fields'.

PMID- 11314846
TI  - Exchanging spare parts or becoming a new person? People's attitudes toward
      receiving and donating organs.
AB  - The present study explored the public's feelings and ideas about receiving
      organs, and how this influenced their attitudes toward accepting a transplant
      themselves. Also the willingness to donate was examined in order to provide a
      complementary perspective. The main aim was to identify consistent attitude
      patterns that would include attitudes toward both receiving and donating organs
      and the motives behind this. Sixty-nine individuals with varying socio
      demographic background, selected from samples who had responded to a
      questionnaire on receiving and donating organs and tissues, were interviewed in
      depth. The approach to analyse the interviews was hermeneutic. Seven typical
      attitude patterns emerged. By an 'attitude pattern' was meant a specific set of
      attitudes and motives, that formed a consistent picture that was logical and
      psychologically meaningful. In the discussion, two different conceptions of the
      body were focused. One of them meant that the body was easily objectified and
      conceived as machine-like, and did not represent the self. This machine model
      paved the way for the understanding that body parts needed to be replaced by
      spare parts. The other conception meant that a new organ would transfer the
      donor's qualities, i.e. influence the identity of the recipient with regard to
      behaviour, appearance, and personality. This belief may be explained by 'analogy
      thinking' based on our everday experience of how mixed entities take on the
      qualities of all components. Another explanation would be a kind of magical
      thinking and 'the law of contagion', which is often connected to oral
      incorporation. The consequences of these conceptions when patients are confronted
      with the factual situation of a transplantation, were discussed.

PMID- 11314847
TI  - Poor people, poor places, and poor health: the mediating role of social networks
      and social capital.
AB  - This paper explores the dynamics between poverty and exclusion; neighbourhood,
      and health and well being by considering the role of social networks and social
      capital in the social processes involved. It is based on qualitative research
      taking two deprived areas as exemplary case studies, and involving depth
      interviews with residents. Neighbourhood influences on networks and social
      capital were explored, network typologies developed reflecting structural and
      cultural aspects of individual's networks, and pathways implicated in health
      effects considered. The complexity of social capital is addressed. The role of
      three factors in influencing social networks and social capital are demonstrated:
      neighbourhood characteristics and perceptions; poverty and social exclusion, and
      social consciousness. Perceptions of inequality could be a source of social
      capital as well as demoralisation. Different network structures-dense and weak,
      homogeneous and heterogeneous- were involved in the creation of social capital
      and had implications for well being. Coping, enjoyment of life and hope are
      identified as benefits. Although participation in organisations was confirmed as
      beneficial, it is suggested that today's heterogeneous neighbourhoods also
      require regenerated local work opportunities to develop bridging ties necessary
      for the genesis of inclusive social capital and better health. Despite the
      capacity of social capital to buffer its harsher effects, the concept is not
      wholly adequate for explaining the deleterious effects of poverty on health and
      well being.

PMID- 11314848
TI  - Efficacy of a minimal intervention to reduce fat intake.
AB  - Effective dietary interventions must be developed to reduce fat intake in whole
      populations, rather than clinical subgroups. This study tested the effects of
      personalised feedback on fat intake in a general population. Hospital workers (n
      = 801) were randomised to receive personalised feedback or no personalised
      feedback. Personalised feedback consisted of one sentence expressing current fat
      intake as a percentage of total calorific intake. Changes in fat intake from
      baseline to five months post-intervention were evaluated. The personalised
      intervention produced significant decreases in total and saturated fat intake,
      compared with the control group. Total-fat decreased by 8.6% (versus 0.2% in the
      control group); saturated fat decreased by 9.3% (versus 1.7% in the control
      group). Fat intake as a proportion of total calorific intake did not decrease
      significantly in either condition. Findings also revealed differential effects of
      feedback on high- versus low-fat consumer groups. Personalised feedback
      significantly reduced fat intake in high-fat consumers, and prevented low-fat
      consumers from increasing their fat intake. Personalised fat feedback therefore
      represents an efficacious and low-intensity approach to the reduction of fat
      intake in the general population.

PMID- 11314849
TI  - HIV/AIDS institutional discrimination in Switzerland.
AB  - A UNAIDS protocol designed to identify discrimination against people living with
      HIV/AIDS was applied in Switzerland, a country where policies against such
      discrimination had been actively promoted since the beginning of the HIV
      epidemic. Discrimination, in its strict legal definition, was examined in nine
      areas of everyday life, and at three levels: legislation, written regulations,
      and actual practices. Data concerning both expert opinion and subjective
      experience of discrimination was gathered by members of an interdisciplinary work
      group by means of: (1) interviews with over 200 key informants and experts,
      covering each of the areas investigated, and (2) actively seeking testimonies as
      to experiences of discrimination through local AIDS groups and through informal
      contacts of work group members. The study revealed little institutional
      discrimination in the region investigated, attesting to the efficacy of clear and
      actively promoted anti-discrimination policies. Individual discrimination and
      stigmatisation persist, however. It is in combating individual discrimination and
      stigmatisation that efforts must now concentrate. The UNAIDS protocol was found
      to be a valuable tool for tracking the sorts of discrimination that can most
      easily be influenced by policy measures.

PMID- 11314850
TI  - Beyond health gain: the range of health system benefits expressed by social
      groups in Mexico and Central America.
AB  - Current health reform proposals in most developing countries stress health gain
      as the chief evaluation criterion. Essential service packages are formulated
      using cost-effectiveness methods for the selection of interventions without
      sufficient regard for other factors that are significant for successful
      implementation and acceptance by the needy. This paper presents the results of
      research undertaken in Mexico and Central America to test the hypothesis that
      population groups view health gain as only one among several benefits derived
      from health systems. The goal at this stage was two-fold: (a) to identify through
      qualitative methods the range of benefits that are significant for a wide cross
      section of social groups and (b) to classify such benefits in types amenable to
      be used in the development of instruments to measure the benefits intended and
      actually produced by health systems. Fourteen focus groups were undertaken in
      Costa Rica, El Salvador, Guatemala, Mexico and Nicaragua representing diverse
      age, gender, occupation and social conditions. Six major types of health system
      benefits were identified besides health gain: reassurance/uncertainty reduction,
      economic security, confidence in health system quality, financial benefits
      derived from the system, health care process utility and health system fairness.
      Benefits most often mentioned can be classed under health care process utility
      and confidence in system quality. They also have the most consensus across social
      groups. Other benefits mentioned have an affinity with social conditions. Human
      resource-derived utility stands out by its frequency in the range of benefits
      mentioned. Health systems and health sector reform proposals must emphasise those
      aspects of quality related to human resources to be in accord with population
      expectations.

PMID- 11314851
TI  - Disadvantaged persons' participation in health promotion projects: some
      structural dimensions.
AB  - A structural perspective was used in studying community participation of
      disadvantaged groups (poor women, street youth, and disabled persons) in health
      promotion projects. Five community projects in the Canadian Health Promotion
      Contribution Program were examined in a comparative case study utilizing in-depth
      interviews, documents, and secondary sources. Analysis revealed relatively low
      numbers and restricted range of participants, difficulties in recruiting and
      maintaining participants, declining rates of active participation over time, and
      limited target group influence and power. This paper reports on the relationship
      between various dimensions of structure (social-cultural, organizational,
      political-legal-economic) and the community participation process. Participation
      was influenced by structural factors such as bureaucratic rules and regulators,
      perceived minority group rights and relations, agency reputations and
      responsibilities, available resources, and organizational roles. Control of
      projects by target group members, rather than by service agencies, was an
      important overall organizational structural factor which allowed community
      members to achieve influence in projects. The study concludes that a conceptual
      model based on structural factors is useful in explaining how key factors from
      federal and local levels can restrict or facilitate the community participation
      process.

PMID- 11314852
TI  - Gender differences in descriptions of angina symptoms and health problems
      immediately prior to angiography: the ACRE study. Appropriateness of Coronary
      Revascularisation study.
AB  - Although the prevalence of angina in women is increasing, women are less likely
      than men to undergo invasive management of coronary disease. Gender differences
      in language use may contribute to disparities in management, since the diagnosis
      of angina relies on a patient's description of their symptoms. This study set out
      to investigate whether gender differences exist in the language used when
      describing angina symptoms and perceived health problems at the time of
      angiography, which might influence the rate of subsequent revascularisation.
      Content analysis was used to analyse written accounts of 'symptoms and health
      problems' in 200 (96 female) patients randomly selected within age strata who
      were undergoing coronary angiography for chronic stable angina in the
      Appropriateness of Coronary Revascularisation (ACRE) study. Written free text was
      coded into seven categories: pain location (chest or arm and throat, neck or
      jaw); pain character; breathlessness; other symptoms; effects on lifestyle;
      symptom attributions; and patient discourses ('story' or 'factual'). Women
      described more throat, neck or jaw pain than men among those with low physical
      functioning ( p=0.06), in the presence of coronary artery disease (p = 0.04) and
      in those who were not subsequently revascularised (p =0.05). Women also gave more
      accounts than men of breathlessness and other symptoms, but there was little
      evidence for gender differences in the use of 'factual' discourses. We conclude
      that from the time of angiography, gender differences in language use do exist
      and description of angina pain may influence subsequent revascularisation.
      Further research is necessary to investigate the nature and consequences of
      gender differences in language use at this and earlier stages in the referral
      process.

PMID- 11314853
TI  - Adolescent perceptions of smoking imagery in film.
AB  - Smoking amongst adolescents in New Zealand continues to be a problem, with more
      than a one-third increase in smoking prevalence between 1992 and 1997. Favourable
      portrayals of smoking in the media have been cited as potential motivators of the
      initiation of smoking among adolescents. To date, however, its role in
      influencing smoking perceptions and behaviours has not received systematic
      analysis. A qualitative study was conducted to explore how adolescents interpret
      and decode smoking imagery in movies. Data was collected through focus groups.
      Same-gender groups of 12- and 13-year-old students were interviewed at their
      schools. Participants discussed their recollections of and responses to
      portrayals of smoking in recently viewed films, as well as their perceptions of
      smoking in general. Students perceived that smoking in film is both highly
      prevalent and recognisable, and they regarded on-screen-smoking imagery as an
      accurate reflection of reality. Adolescents in this study were predominantly
      nonchalant towards the inclusion of smoking images in film, and they perceived an
      unrealistically high prevalence of smoking amongst peers and adults. Their
      noncholant response is linked with the perception that smoking is normal and
      prevalent and with the broad understanding of the constructed nature of media
      imagery. Smoking imagery in film may play a critical role in reinforcing cultural
      interpretations of tobacco use, such as its role as a means of stress relief,
      development of self-image and as a marker of adult independence.

PMID- 11314854
TI  - Organochlorines and breast cancer: the uses of scientific evidence in
      claimsmaking.
AB  - This paper explores the role and utilization of scientific evidence concerning
      one of the potential adverse health impacts (breast cancer) of the use of
      chlorine through examining the aims of an environmental group, Greenpeace, and
      its opponents. Specifically, the paper identifies the claims of Greenpeace and
      the scientific evidence used to justify those claims in its (Thornton, 1993)
      report Chlorine, Human Health and the Environment: The Breast Cancer Warning. A
      media analysis was conducted over a ten year period to assess what counter-claims
      were generated. The claimsmaking activities of breast cancer advocacy groups,
      scientists, pro-chlorine groups, and environmentalists were monitored. To counter
      the Greenpeace claims, pro-chlorine supporters argued for the responsible use of
      science, and redefined the chlorine issue as one of public health and economic
      security. The counter-claims between the supporters and the opponents of the
      chlorine issue stemmed from differences in their agendas, values, and solutions
      proffered in the environmental health policy domain.

PMID- 11314855
TI  - X-rays induce dose-dependent and cell cycle-independent accumulation of
      p21(sdi1/WAF1).
AB  - Cell cycle arrest at the G1 checkpoint is governed by a function of wild-type
      p53. We assessed the behavior of the sdi1 gene, which codes for a 21kDa potent
      inhibitor of cdk/cyclins, after X-irradiation. X-irradiation induced sdi1 mRNA
      accumulation and G1 arrest only in cells possessing wild-type p53. Elevation of
      p21(sdi1/WAF1) was preceded by p53 accumulation, which occurred despite p53 mRNA
      constancy in normal cells growing in the log phase. The quantity of accumulated
      p53 and p21(sdi1/WAF1) was radiation dose dependent. A decrease in the S phase
      cell population in normal cells observed after irradiation reached a minimum at
      less-than-maximum levels of p53 and p21(sdi1/WAF1). Furthermore, an accumulation
      of p53 and p21(sdi1/WAF1) was also observed when cells were synchronized in the
      G0, G1 and S phase and X-irradiated. These results indicated that an X-ray
      induced p53 and p21(sdi1/WAF1) accumulation mechanism exists throughout the cell
      cycle, and that the signal strength induced by X-irradiation is dose-dependent.

PMID- 11314856
TI  - Alterations in palatal ruga patterns in Jcl:ICR mouse fetuses from dams treated
      with all-trans-retinoic acid.
AB  - Pregnant Jcl:ICR mice were orally given all-trans-retinoic acid (RA) at dose
      levels from 0.08 to 80 mg/kg once at days 10.5, 11.5, or 12.5 (vaginal plug = day
      0) of gestation. The dams were sacrificed at day 18.5 of gestation, and the
      fetuses were dissected. After fixation in Bouin's solution, the fetal palates
      were observed under a dissecting microscope. Pattern alterations rare in the
      control fetuses were shortness, fusion, maldirection, trirugal malalignment,
      modified cross, and cross. These alterations were defined as abnormalities. Cleft
      palate was induced at dose levels of 20 mg/kg and above. At each treatment day,
      the total incidence of abnormal rugae increased from the dose of 0.3 or 0.6
      mg/kg, dose-dependently. Although missing ruga-8 was a common pattern alteration
      in vehicle controls, its incidence increased dose-dependently. The incidence of
      supernumerary posterior to ruga 3 increased dose-dependently after treatment at
      day 11.5 or day 12.5 of gestation, however the increase was not observed after
      treatment at day 10.5 of gestation. These findings indicate that the
      abnormalities of ruga, missing ruga-8 and supernumerary posterior to ruga 3 are
      very sensitive indicators of teratogenicity of RA.

PMID- 11314857
TI  - Characteristic magnetic resonance imaging for neurological assessment in HELLP
      syndrome with eclampsia: a case report.
AB  - HELLP syndrome is a complication of pregnancy characterized by hemolytic anemia,
      elevated liver enzymes, and low platelets. We describe a patient who suffered a
      generalized tonic seizure as a clinical onset. Magnetic resonance imaging (MRI)
      of the brain showed high intensity lesions on T2-weighted images and low- and iso
      intensity on T1-weighed images. The patient fully recovered and on follow-up MRI
      the abnormal lesions were almost totally resolved. The sensitivity and
      specificity of MRI is useful in distinguishing this complication of pregnancy
      from cerebral apoplexy, brain tumor, epilepsy and other causes.

PMID- 11314858
TI  - An international data analysis on the level of maternal and child health in
      relation to socioeconomic factors.
AB  - International data on health and socioeconomic factors were analyzed to
      understand the trends and the determinants of maternal and infant mortality in
      the late years. Multivariate analyses were carried out to summarize the structure
      of the data. Multiple regression analyses were also carried out with these two
      mortality rates as dependent variables. The range of independent variables
      included health resource availability, immunization, GNP, illiteracy rates,
      distribution in working area, the indicators of living standards such as
      percentage of telephone lines and television sets per capita and the percentages
      of working children, population with access to safe water and sanitation, people
      living in urban areas, among others. In the preliminary analysis the indicators
      of living standards appeared highly correlated to maternal and infant mortality.
      Working area (industrial or agricultural) showed also an important correlation.
      In factor analysis indirect variables (economic and living condition) were
      summarized into two factors. Two regression analyses were executed. In the first
      the variables were used directly, while factors obtained by the factor analysis
      were used in the second. The second analysis confirmed the previous analysis:
      fertility rate, immunization and urbanization appeared as determinants of
      maternal mortality. Birth rate, percentage of females working in agriculture and
      total illiteracy appeared as determinants of infant mortality. The factors
      extracted in the factor analysis made a significant contribution to the second
      regression analysis. We concluded: 1) The factors extracted by factor analyses
      from indirect variables had high explanatory ability on infant mortality rates,
      2) The presence of immunization together with birth rate and fertility rate in
      the regression models pointed out the importance of investing in birth rate
      reduction and disease prevention methods.

PMID- 11314859
TI  - Scabies associated with radiation therapy for cutaneous T-cell lymphoma.
AB  - Scabies, infection with Sarcoptes scabiei, is known to be predisposed to by poor
      body hygiene, environmental exposure, and systemic immunodeficiency. We report
      the case of an 83-year-old man with Sezary's syndrome who developed scabies
      limited to the skin of the upper chest, the same location where he had previously
      received electron beam radiation treatments for cutaneous T-cell lymphoma.
      Histologic and immunohistochemical studies demonstrated that sections of the
      previously irradiated right and left chest skin, compared to non-irradiated
      chest, abdominal, and leg skin, had infestation by scabies, diminished
      involvement by T-cell lymphoma, and notably reduced numbers of Langerhans cells.
      These findings suggest that the development of scabies may be predisposed to by
      local cutaneous radiation therapy, and that it may be mediated by local cutaneous
      immunodeficiency secondary to reduced numbers of Langerhans cells.

PMID- 11314860
TI  - Fibrin sealant: clinical use and the development of the University of Virginia
      Tissue Adhesive Center.
AB  - The utilization of fibrin sealants to augment hemostasis, seal tissues, and
      facilitate targeted delivery of drugs is increasing. In 1985, a hospital-based
      program was established to provide autologous and allogeneic cryoprecipitate that
      serves as a fibrin sealant when combined with bovine thrombin. To date, more than
      4,000 patients have been treated with this product at our institution, with an
      efficacy rate greater than 90%. Collaboration among surgical services and the
      blood bank fostered multispecialty expertise with this product that led, in 1997,
      to the establishment of the University of Virginia Tissue Adhesive Center. The
      Tissue Adhesive Center is a multidisciplinary center whose physician director and
      nursing and administrative support staff facilitate basic research, laboratory
      investigation, and preclinical and clinical trials with collaborators throughout
      the university. The Tissue Adhesive Center also provides educational programs and
      clinical consultation, and tracks and participates in peer review of sealant use.
      The licensure of a commercially produced, virally inactivated, pooled-plasma
      fibrin sealant in May 1998 provided an alternative source of adhesive.
      Utilization of the commercial product surpassed use of the blood bank product in
      April 1999. At present, use of the commercial product is approximately 3 times
      that of the blood bank-produced sealant. This report reviews the clinical uses of
      fibrin sealant, its regulatory history, the production of fibrin sealants, the
      evolution of a blood bank fibrin sealant program, the development of the Tissue
      Adhesive Center, and the utilization of commercial and blood bank-produced
      sealant at our university hospital.

PMID- 11314861
TI  - Protecting human research subjects.
AB  - Respect for persons, beneficence, and justice are the cardinal principles that
      guide the ethical conduct of research on humans. Past abuses of human research
      subjects prompted medical organizations and governmental agencies to develop
      guidelines that ensure the protection of human research subjects. Human research
      funded by the U.S. government is strictly regulated, and Institutional Review
      Board approval of the experimental protocol is required prior to the award. Under
      limited circumstances, human research may be exempted from review, or review may
      be expedited. Research involving specimens submitted for pathological examination
      or diagnostic studies sometimes qualifies for these special categories of limited
      review. Academic pathologists and laboratorians should be aware of the
      regulations that apply to research on human subjects.

PMID- 11314862
TI  - Mitochondrial medicine--molecular pathology of defective oxidative
      phosphorylation.
AB  - Different tissues display distinct sensitivities to defective mitochondrial
      oxidative phosphorylation (OXPHOS). Tissues highly dependent on oxygen such as
      the cardiac muscle, skeletal and smooth muscle, the central and peripheral
      nervous system, the kidney, and the insulin-producing pancreatic beta-cell are
      especially susceptible to defective OXPHOS. There is evidence that defective
      OXPHOS plays an important role in atherogenesis, in the pathogenesis of
      Alzheimer's disease, Parkinson's disease, diabetes, and aging. Defective OXPHOS
      may be caused by abnormal mitochondrial biosynthesis due to inherited or acquired
      mutations in the nuclear (n) or mitochondrial (mt) deoxyribonucleic acid (DNA).
      For instance, the presence of a mutation of the mtDNA in the pancreatic beta-cell
      impairs adenosine triphosphate (ATP) generation and insulin synthesis. The
      nuclear genome controls mitochondrial biosynthesis, but mtDNA has a much higher
      mutation rate than nDNA because it lacks histones and is exposed to the radical
      oxygen species (ROS) generated by the electron transport chain, and the mtDNA
      repair system is limited. Defective OXPHOS may be caused by insufficient fuel
      supply, by defective electron transport chain enzymes (Complexes I - IV), lack of
      the electron carrier coenzyme Q10, lack of oxygen due to ischemia or anemia, or
      excessive membrane leakage, resulting in insufficient mitochondrial inner
      membrane potential for ATP synthesis by the F0F1-ATPase. Human tissues can
      counteract OXPHOS defects by stimulating mitochondrial biosynthesis; however,
      above a certain threshold the lack of ATP causes cell death. Many agents affect
      OXPHOS. Several nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit or uncouple
      OXPHOS and induce the 'topical' phase of gastrointestinal ulcer formation.
      Uncoupled mitochondria reduce cell viability. The Helicobacter pylori induces
      uncoupling. The uncoupling that opens the membrane pores can activate apoptosis.
      Cholic acid in experimental atherogenic diets inhibits Complex IV, cocaine
      inhibits Complex I, the poliovirus inhibits Complex II, ceramide inhibits Complex
      III, azide, cyanide, chloroform, and methamphetamine inhibit Complex IV. Ethanol
      abuse and antiviral nucleoside analogue therapy inhibit mtDNA replication. By
      contrast, melatonin stimulates Complexes I and IV and Gingko biloba stimulates
      Complexes I and III. Oral Q10 supplementation is effective in treating
      cardiomyopathies and in restoring plasma levels reduced by the statin type of
      cholesterol-lowering drugs.

PMID- 11314863
TI  - Nasal toxicity, carcinogenicity, and olfactory uptake of metals.
AB  - Occupational exposures to inhalation of certain metal dusts or aerosols can cause
      loss of olfactory acuity, atrophy of the nasal mucosa, mucosal ulcers, perforated
      nasal septum, or sinonasal cancer. Anosmia and hyposmia have been observed in
      workers exposed to Ni- or Cd-containing dusts in alkaline battery factories,
      nickel refineries, and cadmium industries. Ulcers of the nasal mucosa and
      perforated nasal septum have been reported in workers exposed to Cr(VI) in
      chromate production and chrome plating, or to As(III) in arsenic smelters.
      Atrophy of the olfactory epithelium has been observed in rodents following
      inhalation of NiSO4 or alphaNi3S2. Cancers of the nose and nasal sinuses have
      been reported in workers exposed to Ni compounds in nickel refining, cutlery
      factories, and alkaline battery manufacture, or to Cr(VI) in chromate production
      and chrome plating. In animals, several metals (eg, Al, Cd, Co, Hg, Mn, Ni, Zn)
      have been shown to pass via olfactory receptor neurons from the nasal lumen
      through the cribriform plate to the olfactory bulb. Some metals (eg, Mn, Ni, Zn)
      can cross synapses in the olfactory bulb and migrate via secondary olfactory
      neurons to distant nuclei of the brain. After nasal instillation of a metal
      containing solution, transport of the metal via olfactory axons can occur
      rapidly, within hours or a few days (eg, Mn), or slowly over days or weeks (eg,
      Ni). The olfactory bulb tends to accumulate certain metals (eg, Al, Bi, Cu, Mn,
      Zn) with greater avidity than other regions of the brain. The molecular
      mechanisms responsible for metal translocation in olfactory neurons and
      deposition in the olfactory bulb are unclear, but complexation by metal-binding
      molecules such as carnosine (beta-alanyl-L-histidine) may be involved.

PMID- 11314864
TI  - Detection of trisomy 8 in philadelphia chromosome-positive CML patients using
      conventional cytogenetic and interphase fluorescence in situ hybridization
      techniques and its relation to c-myc involvement.
AB  - Trisomy 8 (+8) is a common clonal evolution marker for progression in chronic
      myelogenous leukemia. The relationship of +8 to various stages of t(9;22)
      leukemias is not firmly established. To explore this association we examined bone
      marrow (BM) cells from 10 Philadelphia chromosome positive (Ph+) chronic myeloid
      leukemia (CML) patients in different stages of the disease, using conventional
      cytogenetic technique(CCT) and interphase fluorescence in situ hybridization
      (FISH). FISH detection of chromosome 8 was accomplished using the D8Z2 (Oncor)
      probe specific for the centrometric region of chromosome 8. Five hundred
      interphase nuclei were counted for each patient. Three of the 10 patients were
      selected for detection of c-myc gene locus located in the 8q24.2-24.3 region
      using the L

PMID- 11314865
TI  - Expression and secretion of RANTES by human peripheral blood CD4+ cells are
      dependent on the presence of monocytes.
AB  - The cDNA for RANTES (an acronym for "Regulated upon Activation, Normal T cell
      Expressed and Secreted") was initially discovered by subtractive hybridization as
      a T cell-specific sequence. Consistent with it being a C-C (beta) chemokine,
      RANTES is a monocyte chemoattractant. In addition, RANTES can chemoattract
      unstimulated CD4+/CD45RO+ memory T cells and stimulated CD4+ and CD8+ T cells
      with the naive and memory phenotypes in immunologically active sites. It has been
      shown that CD8+ cells are dominant sources of RANTES. Here we attempted to
      determine if CD4+ cells express and secrete RANTES alone, or if other accessory
      cells (activated monocytes) are needed to activate them. We found that when
      autologous monocytes are added to CD4+ cells and then stimulated with
      phytohaemagglutinin (PHA), the quantity of RANTES, in terms of transcription and
      translation of the protein, is significantly higher than the amount produced by
      the PHA-activated monocytes alone; isolated CD4+ cells stimulated with PHA do not
      produce any appreciable quantity of RANTES. When CD4+ cells are primed overnight
      with monocytes and then stimulated with PHA, they produce more RANTES compared to
      PHA-stimulated CD4+ cells alone. The influence that monocytes have on CD4+ cells
      to produce RANTES was confirmed when the physiological activator, tumor necrosis
      factor-alpha (TNF-alpha), was used. These data show that CD4+ cells need
      monocytes to express and secrete appreciable amounts of RANTES.

PMID- 11314866
TI  - The influence of lipid composition and divalent cations on annexin V binding to
      phospholipid mixtures.
AB  - Annexin V is a 36-kDa protein which, it has been suggested, is a factor in
      protecting the vascular endothelium from attack by antibodies to other
      phospholipid-binding proteins. Competition between annexin V and beta2
      glycoprotein I (beta2GPI) for phospholipid surfaces is complicated by empirical
      observations regarding alterations in binding to anionic phospholipid, primarily
      phosphatidylserine. In order to elucidate the effect of phospholipid composition
      and divalent cations (Ca(+2) and Mg(+2)) on annexin V binding to phospholipid, we
      used biotinylated annexin V and peroxidase-conjugated avidin D to probe the
      binding of annexin V to phospholipid-coated wells of polystyrene microtiter
      plates. Binding of annexin V to anionic phospholipid is Ca(+2)-dependent and, in
      its absence, annexin V was found to bind most avidly to 100% phosphatidylcholine
      in a saturable manner, followed by decreasing percentages of phosphatidylcholine.
      Ca(+2) was found to inhibit phosphatidylcholine binding and promote the binding
      of phospholipid mixtures containing phosphatidylserine. Phosphatidylserine (100%)
      did not bind annexin V as strongly as mixtures of 50% and 75% phosphatidylserine.
      The effect with Ca(+2) suggests saturation of Ca(+2)-binding sites on annexin V,
      reached under our experimental conditions at approximately 1 mM. Under the same
      conditions, Mg(+2) slightly enhanced the binding of all of the phospholipid
      compositions studied. Ca(+2)-dependent binding of annexin V was competitively
      inhibited by Mg(+2); 5 mM Mg(+2) reduced binding significantly (p < 0.0001 by
      ANOVA, p < 0.05 for post hoc test of 5 mM vs 0 mM). These data suggest that the
      translocation of membrane phospholipid under the dynamics of ion transport in
      vascular endothelium may alter annexin V binding.

PMID- 11314867
TI  - Presence of potential nickel-responsive element(s) in the mouse MTH1 promoter.
AB  - The murine MTH1 gene codes for MTH1, an 8-oxo-2'-deoxyguanosine 5'-triphosphate
      pyrophosphohydrolase (8-oxo-dGTPase) which hydrolyzes 8-oxo-dGTP, a promutagenic
      product of reactive oxygen species' attack on the nucleotide pool. This gene is
      regulated by oxidative stress. Therefore, we hypothesized that MTH1 expression
      can be affected by carcinogenic nickel(II), known to induce such stress. Three
      plasmid constructs, carrying different upstream regions of the mouse MTH1 and the
      chloramphenicol acetyltransferase (CAT) reporter gene, were transiently
      transfected into NIH 3T3 cells and the CAT protein was measured in nickel(II)
      acetate-treated and untreated cells. Nickel concentration-dependent increase of
      CAT protein level was observed for low Ni(II) concentrations, up to 400 microM
      Ni(II), in cells transfected with pHI103 plasmid (-5969 to +530 of the MTH1
      sequence) only. Cells transfected with the pHI104 (-1331 to +530) or pHI108 (-151
      to +530) plasmids did not respond to nickel(II) whatsoever. This finding
      demonstrated that the MTH1 sequence between -5969 and -1331 contained element(s)
      responsive to nickel(II) treatment. DNA sequencing revealed the presence of AP-1,
      NF-kappaB, and ATF-1 binding sites in both the -5969 to -1331 and -1331 to +530
      regions. In contrast, two (CA)n repeats (-5642 to -5582 and -2078 to -2031), a
      family of B2 (-5428 to -5247) and B1 (-4559 to -4420) short interspersed repeated
      elements, and an (AT)n repeat (-5243 to -5230) were identified only in the -5969
      to -1331 sequence. The results suggest that up-regulation of murine MTH1
      expression by nickel(II) is controlled by the repeat sequences, potential
      candidates for nickel-responsive elements.

PMID- 11314868
TI  - Decreasing the variability observed in urine analysis.
AB  - Urine analysis is affected significantly by biological variability. The objective
      of this study was to study the feasibility of reducing the biological variability
      of excretion of various analytes in urine, especially albumin in children with
      diabetes, by mixing small volumes of early morning samples. Twenty-two male
      children with type 1 diabetes collected early morning aliquots of approximately
      10 ml of urine on 3 consecutive days and kept them refrigerated in sealed
      containers. The urine collection was repeated every 4-6 months in the diabetic
      children. Ten normal children and 10 normal adults participated as controls. The
      specimens were analyzed individually and as mixed samples for each subject.
      Mixing the 3 urine samples before analysis decreased the biological variability
      of all urine assays (albumin, glucose, creatinine, total protein, potassium). The
      diabetic children had 3 times higher variability of urine albumin (as a ratio to
      creatinine) compared to normal children, when the urine samples were collected
      individually (61% vs 19%, respectively). The variability in the diabetic children
      decreased when the 3 specimens were analyzed as a single sample after mixing,
      especially when urine albumin was expressed as a ratio to creatinine. Blood
      glycated hemoglobin levels correlated better with urine glucose levels when 3
      urine samples were mixed before analysis.

PMID- 11314869
TI  - Recent advances in the science of ECT: can the findings be generalized?

PMID- 11314870
TI  - Prediction of the utility of a switch from unilateral to bilateral ECT in the
      elderly using treatment 2 ictal EEG indices.
AB  - BACKGROUND: The choice of whether to administer nondominant unilateral (UL) or
      bilateral (BL) ECT remains controversial. METHODS: A study in which moderately
      suprathreshold UL nonresponders at treatment 6 were randomized to UL or BL ECT
      offered the opportunity to explore whether ictal EEG indices at treatment 2 might
      predict response to UL ECT, and also which UL ECT nonresponders are likely to
      respond to BL ECT. RESULTS: We found that less postictal suppression in response
      to the second UL ECT stimulus was predictive of a poorer subsequent therapeutic
      response to UL ECT, but of a better therapeutic response if switched to BL ECT. A
      multivariate ictal EEG model was developed that had a significant capacity to
      differentiate those who will respond to UL ECT versus those who will not respond
      to UL ECT, but who will be therapeutic responders when switched to BL ECT.
      CONCLUSIONS: This study raises the possibility that ictal EEG indices at
      treatment 2 may identify situations when UL ECT is physiologically and
      therapeutically inadequate, and when BL ECT is likely to be more effective. The
      determination of whether such predictive physiologic models are of clinical
      utility for the prediction of outcome awaits further study.

PMID- 11314871
TI  - The development and retrospective testing of an electroencephalographic seizure
      quality-based stimulus dosing paradigm with ECT.
AB  - The optimization of electroconvulsive therapy (ECT) stimulus dosing remains
      uncertain. Previous work suggests the potential utility of ictal EEG models of
      seizure adequacy, but such models have never been tested for their ability to
      improve the clinical dosing of ECT treatments. Using data from 149 depressed
      patients, the authors developed an ictal electroencephalographic (EEG) model that
      can discriminate seizures produced by more therapeutically effective and less
      efficacious types of stimuli. They retrospectively determined how stimulus dosing
      according to this seizure adequacy-based model would have differed from that
      actually used in an additional 61 patients who received ECT according to a
      standard clinical dose-titration and EEG seizure duration-based dosing strategy.
      Although the model indicated an increase in stimulus intensity at some point
      during the ECT treatment course in 23 of 61 patients, only 5 of these 23 actually
      received a clinical increase in stimulus intensity. The patients who did not
      receive this increase had a significantly diminished therapeutic response
      compared with the other patients. Conversely, the model also indicated that an
      increase in stimulus intensity that occurred clinically might have been
      unnecessary to achieve therapeutic efficacy in 11% of the patients. This study
      provides preliminary evidence that ictal EEG models have the potential to make
      clinically relevant seizure adequacy distinctions among ECT treatments. Further
      prospective work is indicated to determine the clinical utility of such models.

PMID- 11314872
TI  - A survey of methohexitone use by anesthetists in the clinical practice of ECT in
      Edinburgh.
AB  - The dosage of methohexitone (methohexital) administered by anesthetic staff was
      surveyed in a consecutive series of 52 patients referred for electroconvulsive
      therapy (ECT) in routine clinical practice in Edinburgh. Patients were weighed
      before the first treatment, and the ratio of administered dose to weight in
      kilograms calculated. Anesthesia was administered by three consultant staff and
      six nonconsultant staff. In only one patient (2%) was the administered dose
      within the range recommended by the Royal College of Psychiatrists (0.75-0.9
      mg/kg), and in only four patients (8%) were the doses within the range
      recommended by the American Psychiatric Association (0.75-1.0 mg/kg). In all
      other patients the dose exceeded these recommended ranges; the average dose was
      1.5 (+/- 0.3) mg/kg. The possible implications of these findings are discussed.

PMID- 11314873
TI  - Administration of citalopram before ECT: seizure duration and hormone responses.
AB  - From theoretical and clinical perspectives, it is important to know if selected
      serotonin-reuptake inhibitors (SSRIs), often administered concurrently with
      electroconvulsive therapy (ECT), modify seizure duration. In a study with a
      double-blind, cross-over design, the authors evaluated the effect of citalopram,
      the most selective SSRI available, on the length of electrically induced seizures
      and on hormone secretion during ECT. Ten depressed women were given either 20 mg
      citalopram or placebo orally 2 hours before the third and fourth ECT sessions.
      Seizure duration was assessed by the cuff technique and from
      electroencephalographic recordings, whereas blood for prolactin, thyrotropin, and
      cortisol assessment was sampled before ECT and 5, 10, 20, 30, 40, and 60 minutes
      after ECT. No adverse effects after the administration of citalopram were
      recorded. The length of seizures was not statistically different in the
      citalopram (29.3+/-8.4 seconds) and placebo sessions (28.2+/-9.4 seconds).
      Neither pre-ECT plasma hormone levels measured 2 hours after citalopram or
      placebo administration nor the patterns of ECT-induced hormone secretions
      differed between the two drug and placebo conditions. The lack of effect of
      citalopram on hormones in this study may be a result of possible deficiencies of
      the monoaminergic (i.e., serotoninergic) systems in depression. Although safety
      and efficacy issues were not fully addressed by coadministering citalopram for
      the long term and throughout the course of ECT, these findings support the view
      that challenges the typical clinical practice of discontinuing SSRIs before ECT.

PMID- 11314874
TI  - Electrical dose and seizure threshold: relations to clinical outcome and
      cognitive effects in bifrontal, bitemporal, and right unilateral ECT.
AB  - In patients allocated blindly and randomly to receive bitemporal, right
      unilateral, or bifrontal electroconvulsive therapy, seizure length,
      electrophysiologic characteristics (dynamic impedance, seizure threshold, and
      changes in threshold), and the degree of suprathreshold stimulation were
      recorded. The relations of these variables to clinical outcome and cognitive
      effects were determined. There were no differences in seizure length between
      groups, and there were no significant correlations between seizure length and any
      measure of clinical response. There were substantial differences between the
      groups in mean charge per treatment, with the right unilateral group receiving
      lower doses than either bilateral group. Convulsion time was inversely related to
      applied charge and the rate of increase in charge. There were no significant
      correlations between impedance, charge, energy, or rate of increase in charge on
      the one hand, and clinical improvement on the other. The increase in threshold
      during the course of treatment was not related to clinical change. Cognitive
      impairment was related to electrical dose only in the bifrontal group, which
      showed the least degree of treatment-induced intellectual dysfunction. Compared
      with bitemporal or right unilateral treatment, bifrontal electroconvulsive
      therapy yields the best ratio of benefits to side effects and should be given at
      threshold level to minimize cognitive loss.

PMID- 11314875
TI  - Efficacy and cognitive effects of right unilateral electroconvulsive therapy.
AB  - The efficacy, memory, and cognitive effects of right unilateral (RUL)
      electroconvulsive therapy (ECT) at 2.5 times threshold in 32 inpatients with
      moderate to severe major depressive disorder were evaluated at baseline, during
      the course of treatment, and 1 month after treatment. Neuropsychological
      assessment included the Randt Memory Test, Personal Memory Test, short-version
      Wechsler Adult Intelligence Scale-Revised, and Self-Rating Scale of Memory
      Functions. At the treatment end point, although the Hamilton Depression Rating
      Scale mean score was decreased by 54.2%. the response rate of 2.5 times threshold
      RUL ECT using stringent criteria was only 31.2%. Treatment was associated with
      significant anterograde memory impairment in the short term. Mean total scores of
      the Randt Memory Test and Personal Memory Test were decreased from baseline by
      14.8% and 32.5%, respectively, after six sessions of ECT. These memory deficits
      were significantly improved by the 1 month follow-up examination. Subjective
      memory scores increased consistently during treatment, correlating with
      improvements in mood. No adverse effects on nonmemory cognition were found.
      Although RUL ECT at 2.5 times threshold is not associated with marked or
      persistent cognitive disturbances, its efficacy may be insufficient in clinical
      practice.

PMID- 11314876
TI  - Lack of significant changes on magnetic resonance scans before and after 2 weeks
      of daily left prefrontal repetitive transcranial magnetic stimulation for
      depression.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a new technology for
      exploring brain function. With this method, a small electromagnet is placed on
      the scalp; by activating and deactivating it, nerve cells in the underlying
      superficial cortex are depolarized. Several studies have found that prefrontal
      rTMS has potential efficacy in treating depression, and this technology, in
      addition to being a research tool, may soon play a role in psychiatric practice.
      Thus, establishing the safety of this technology is important and has been
      studied insufficiently. The authors performed T1-weighted three-dimensional
      volumetric magnetic resonance (MR) imaging on 22 depressed adults (15 active, 7
      control) before and after they participated in a 2-week double-blinded, placebo
      controlled trial of daily left prefrontal rTMS for the treatment of depression (a
      total of 16,000 stimuli). Seventeen patients also had paired T2-weighted scans.
      In a blinded manner, MR scans were qualitatively and quantitatively assessed for
      structural changes. No qualitative structural differences were observed before
      and after treatment. In addition, volumetric analysis of the prefrontal lobe
      showed no changes in the 2 weeks of the study. In conclusion, 10 days of daily
      prefrontal rTMS at these intensities and frequencies does not cause observable
      structural changes on MR scans in depressed adults.

PMID- 11314878
TI  - Treatment and suicide in severe depression: a case-control study of
      antidepressant therapy at last contact before suicide.
AB  - Treatment at last contact in 89 persons with severe depression who committed
      suicide was compared with treatment at a corresponding date in 89 matched persons
      who did not commit suicide. No difference in electroconvulsive therapy use or
      prescription of antidepressant medication could be shown between those who
      committed suicide and those who did not. Neither was there a difference in
      response to treatment as measured in rates of improvement with treatment.
      However, continued treatment with antidepressant medication after
      electroconvulsive therapy was more common in the persons who did not commit
      suicide than in those who did (46% versus 13%, p < 0.025). None of the persons
      who committed suicide who were followed during the 6 months before death had
      received continued treatment after electroconvulsive therapy. This study lends
      statistical support to the importance of continuing treatment after
      electroconvulsive therapy to prevent suicide.

PMID- 11314877
TI  - The effects of electroconvulsive therapy on melatonin.
AB  - Although several studies have investigated the impact of various antidepressant
      medications on melatonin, there are no published reports addressing the effects
      of electroconvulsive therapy (ECT). Melatonin's major urinary metabolite, 6
      sulfatoxymelatonin (6MT), was measured before and after an acute course of ECT.
      Fourteen subjects diagnosed with major depression who had failed prior
      pharmacologic therapy were enrolled. 6MT excretion was measured using an enzyme
      linked immunosorbent assay test in 24 hour samples separated into daytime and
      nighttime components. Hamilton Rating Scale for Depression scores showed a
      significant improvement (p < 0.0001). Data analysis using the Wilcoxon signed
      rank test demonstrated a significant decrease in 24 hour 6MT post-ECT (p < 0.016)
      and daytime 6MT (p < 0.008). These results demonstrate an association between a
      therapeutic response to ECT and decrease in endogenous melatonin production.

PMID- 11314879
TI  - ECT post eye surgery: two cases and a review of the literature.
AB  - Little is known about the safety of electroconvulsive therapy (ECT) following any
      surgical procedure. We present two cases of elderly patients who required
      treatment with ECT shortly after eye surgery. One patient received ECT 12 days
      post cataract surgery. The other patient received ECT 1 week post vitrectomy on
      one eye, and then a few years after that she received ECT 2.5 weeks post cataract
      surgery on the other eye. There were no complications or adverse events for
      either patient. We review the existing literature on the effects of ECT on
      intraocular pressure and discuss the implications on patients who have recently
      undergone ophthalmic surgery.

PMID- 11314880
TI  - Electroconvulsive therapy in the acute poststroke period.
AB  - A depressed patient was successfully treated with electroconvulsive therapy
      approximately 7 to 14 days after a cerebellar stroke. This report documents an
      uncomplicated use of electroconvulsive therapy that was well tolerated and
      effective in a course of eight treatments in the acute poststroke period.

PMID- 11314881
TI  - Treatment of major depression complicated by bilateral foot drop and double
      incontinence with ECT.
AB  - This report describes a 56-year-old man with severe depression who developed
      bilateral foot drop, dual incontinence, and swallowing difficulties, which
      required several physical investigations and consultations before an excellent
      response to electroconvulsive therapy occurred with reversal of all symptoms.

PMID- 11314882
TI  - Use of ECT after maxillofacial repair.

PMID- 11314883
TI  - Relationship of cigarette smoking to attachment level profiles.
AB  - OBJECTIVES: The present investigation examined clinical features of periodontal
      disease and patterns of attachment loss in adult periodontitis subjects who were
      current, past or never smokers. MATERIAL AND METHODS: 289 adult periodontitis
      subjects ranging in age from 20-86 years with at least 20 teeth and at least 4
      sites with pocket depth and/or attachment level >4 mm were recruited. Smoking
      history was obtained using a questionnaire. Measures of plaque accumulation,
      overt gingivitis, bleeding on probing, suppuration, probing pocket depth and
      probing attachment level were taken at 6 sites per tooth at all teeth excluding
      3rd molars at a baseline visit. Subjects were subset according to smoking history
      into never, past and current smokers and for certain analyses into age categories
      <41, 41-49, >49. Uni- and multi-variate analyses examined associations between
      smoking category, age and clinical parameters. RESULTS: Current smokers had
      significantly more attachment loss, missing teeth, deeper pockets and fewer sites
      exhibiting bleeding on probing than past or never smokers. Current smokers had
      greater attachment loss than past or never smokers whether the subjects had mild,
      moderate or severe initial attachment loss. Increasing age and smoking status
      were independently significantly related to mean attachment level and the effect
      of these parameters was additive. Mean attachment level in non smokers <41 years
      and current smokers >49 years was 2.49 and 4.10 mm respectively. Stepwise
      multiple linear regression indicated that age, pack years and being a current
      smoker were strongly associated with mean attachment level. Full mouth attachment
      level profiles indicated that smokers had more attachment loss than never smokers
      particularly at maxillary lingual sites and at lower anterior teeth. CONCLUSIONS:
      In accord with other studies, smokers had evidence of more severe periodontal
      disease than past or never smokers. At all levels of mean attachment loss,
      smokers exhibited more disease than never smokers. Difference in mean attachment
      level between smokers and never smokers at individual sites was not uniform.
      Significantly more loss was observed at maxillary lingual sites and lower
      anterior teeth suggesting the possibility of a local effect of cigarette smoking.

PMID- 11314884
TI  - Amoxicillin plus metronidazole in the treatment of adult periodontitis patients.
      A double-blind placebo-controlled study.
AB  - BACKGROUND, AIMS: The aim of this double-blind, parallel study was to evaluate
      the adjunctive effects of systemically administered amoxicillin and metronidazole
      in a group of adult periodontitis patients who also received supra- and
      subgingival debridement. METHODS: 49 patients with a diagnosis of generalised
      severe periodontitis participated in the study. Random assignment resulted in 26
      patients in the placebo (P) group with a mean age of 40 years and 23 patients in
      the test (T) group which had a mean age of 45 years. Clinical measurements and
      microbiological assessments were taken at baseline and 3 months after completion
      of initial periodontal therapy with additional placebo or antibiotic treatment.
      Patients received coded study medication of either 375 mg amoxicillin in
      combination with 250 mg metronidazole or identical placebo tablets, every 8 hours
      for the following 7 days. RESULTS: At baseline, no statistically significant
      differences between groups were found for any of the clinical parameters. Except
      for the plaque, there was a significantly larger change in the bleeding, probing
      pocket depth (PPD) and clinical attachment level (CAL) in the T-group as compared
      to the P-group after therapy. The greatest reduction in PPD was found at sites
      with initial PPD of > or = 7 mm, 2.5 mm in the P-group and 3.2 mm in the T-group.
      The improvement in CAL was most pronounced in the PPD category > or = 7 mm and
      amounted to 1.5 mm and 2.0 mm in the P- and T-groups, respectively. No
      significant decrease was found in the number of patients positive for any of the
      test species in the P-group. The number of patients positive for Porphyromonas
      gingivalis, Bacteroides forsythus and Prevotella intermedia in the T-group showed
      a significant decrease. After therapy there was a significant difference between
      the P- and the T- group in the remaining number of patients positive for P.
      gingivalis, B. forsythus and Peptostreptococcus micros. 4 subgroups were created
      on the basis of the initial microbiological status for P. gingivalis positive (Pg
      pos) and negative patients (Pg-neg) in the P- and the T-groups. The difference in
      reduction of PPD between Pg-pos and Pg-neg patients was particularly evident with
      respect to the changes in % of sites with a probing pocket depth > or = 5 mm.
      This % decreased from 45% at baseline to 23% after treatment in the Pg-pos
      placebo subgroup and decreased from 46% to 11% in the Pg-pos test subgroup (p <
      or = 0.005). In contrast, the changes in the proportions of sites with a probing
      pocket depth > or = 5 mm in the Pg-neg placebo and Pg-neg test subgroup were
      similar, from 43% at baseline to 18% after treatment versus 40% to 12%
      respectively. CONCLUSIONS: This study has shown that systemic usage of
      metronidazole and amoxicillin, when used in conjunction with initial periodontal
      treatment in adult periodontitis patients, achieves significantly better clinical
      and microbiological results than initial periodontal treatment alone. Moreover,
      this research suggests that especially patients diagnosed with P. gingivalis
      benefit from antibiotic treatment.

PMID- 11314885
TI  - The effect of periodontal treatment on glycemic control in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND, AIMS: This study was designed to explore the effect of periodontal
      therapy on glycemic control in persons with type 2 diabetes mellitus (DM).
      METHODS: 36 patients with type 2 DM (treatment group) received therapy for adult
      periodontitis during an 18-month period. A 36-person control group was randomly
      selected from the same population of persons with type 2 DM who did not receive
      periodontal treatment. RESULTS: These groups were well matched for most of the
      parameters investigated. During the nine-month observation period, there was a
      6.7% improvement in glycemic control in the control group when compared to a
      17.1% improvement in the treatment group, a statistically significant difference.
      Several parameters that could confound or moderate this glycemic control were
      explored. These included the treatment of non-dental infections, weight and
      medication changes. No moderating effect was associated with any of these
      variables. However, there were too few subjects in the study to have the
      statistical power necessary to assess these possible moderators of glycemic
      control. CONCLUSIONS: We interpret the data in the study to suggest that
      periodontal therapy was associated with improved glycemic control in persons with
      type 2 DM.

PMID- 11314886
TI  - Isolation and genotyping of black-pigmented anaerobes from periodontal sites of
      HIV-positive and non-infected subjects in Thailand.
AB  - BACKGROUND, AIMS: The aims of this study were to investigate the prevalence of
      periodontitis, the prevalence of black-pigmented anaerobes and the genotypes of
      Porphyromonas gingivalis and Prevotella intermedia present in HIV-infected and
      control subjects in a heterosexual Thai population. METHOD: 50 AIDS patients and
      50 control subjects were included in the study. Their periodontal condition was
      examined by assessment of bleeding on probing, attachment loss and probing depth,
      and presence of erythema around 6 teeth (16, 21, 24, 36, 41, 44). Subgingival
      plaque was collected from the mesiobuccal sites of these teeth and was cultured
      anaerobically for black-pigmented bacteria. Species were characterised using
      biochemical profiles and total protein profiles. Genotyping of each isolate was
      performed using PCR techniques. RESULTS: There was little clinical evidence of
      HIV-associated periodontitis in the HIV-positive subjects and no difference was
      found in the prevalence or genotype distribution of black-pigmented anaerobes
      between HIV-infected and control subjects. CONCLUSIONS: These data suggest lack
      of severe periodontal destruction due to HIV-infection in Thailand and that these
      subjects are not colonised by more numerous or characteristic clones of certain
      putative periodontal pathogens.

PMID- 11314887
TI  - The erosive effects of some mouthrinses on enamel. A study in situ.
AB  - BACKGROUND: There are both anecdotal clinical and laboratory experimental data
      suggesting that low pH mouthrinses cause dental erosion. This evidence is
      particularly relevant to acidified sodium chlorite (ASC) formulations since they
      have plaque inhibitory properties comparable to chlorhexidine but without the
      well known local side effects. AIM: Studies in situ and in vitro were planned to
      measure enamel erosion by low pH mouthrinses. The study in situ measured enamel
      erosion by ASC, essential oil and hexetidine mouthrinses over 15-day study
      periods. The study was a 5 treatment, single blind cross over design involving 15
      healthy subjects using orange juice, as a drink, and water, as a rinse, as
      positive and negative controls respectively. 2 enamel specimens from unerupted
      human third molar teeth were placed in the palatal area of upper removable
      acrylic appliances which were worn from 9 a.m. to 5 p.m., Monday to Friday for 3
      weeks. Rinses were used 2x daily and 250 ml volumes of orange juice were imbibed
      4x daily. Enamel loss was determined by profilometry on days 5, 10 and 15. The
      study in vitro involved immersing specimens in the 4 test solutions together with
      a reduced acid ASC formulation for a period of 4 h under constant stirring;
      Enamel loss was measured by profilometry every hour. RESULTS: Enamel loss was in
      situ progressive over time with the 3 rinses and orange juice but negligible with
      water. ASC produced similar erosion to orange juice and significantly more than
      the two proprietary rinses and water. The essential oil and hexetidine rinses
      produced similar erosion and significantly more than water. Enamel loss in vitro
      was progressive over time, and the order from low to high erosion was reduced
      acid ASC, ASC, Essential oil, and hexetidine mouthrinses and orange juice.
      CONCLUSION: Based on the study in situ, it is recommended that low pH mouthrinses
      should not be considered for long term or continuous use and never as pre
      brushing rinses. In view of the plaque inhibitory efficacy of ASC, short- to
      medium-term applications similar to those of chlorhexidine would be envisaged.

PMID- 11314888
TI  - Plaque removal with the uninstructed use of electric toothbrushes: comparison
      with a manual brush and toothpaste slurry.
AB  - BACKGROUND: Individuals purchasing electric toothbrushes for the 1st time will
      mostly only have the manufacturer's instructional leaflet for information of
      usage. AIMS: This study was designed to simulate the 1st-time purchase and early
      use of an electric toothbrush with the aim of comparing plaque removal with a
      manual toothbrush. Secondary aims were to assess chemical plaque removal effects
      of a toothpaste slurry and to compare between 2 electric brushes which differed
      only in head speed. METHODS: A group of 16 dentate subjects participated in this
      single-examiner blind, randomised, crossover design balanced for residual
      effects. Subjects had "average" oral hygiene and had never used an electric
      toothbrush previously. 7 days prior to the study, all subjects received the
      slower oscillating rotating toothbrush under test to use at home as they wished.
      The test treatments were brushing with 2 oscillating rotating electric
      toothbrushes, a manual toothbrush and a rinse with a toothpaste slurry (3 g/10 ml
      water). On day 1 of each study period, subjects were rendered plaque-free,
      suspended oral hygiene and returned on day 5. Plaque was scored at baseline by
      index and area and after 30 s, 30 s (total 60 s) and 60 s (total 120 s) of the
      cleaning treatments. Washout periods were at least 2 1/2 days. RESULTS: Highly
      significant treatment differences were found between the 4 treatments because the
      toothpaste slurry was totally without effect. Analyses between the 3 brush
      treatments overall revealed no consistent significant differences. The data
      suggest that in the early days of electric toothbrush use, subjects perform no
      better than using a manual brush. CONCLUSIONS: The present study, taken with
      results from others showing greater benefits from the use of electric brushes,
      supports the idea that dental professionals should, where possible, provide
      advice and instruction in the use of such devices.

PMID- 11314889
TI  - Cigarette smoking, salivary/gingival crevicular fluid cotinine and periodontal
      status. A 10-year longitudinal study.
AB  - BACKGROUND, AIMS: The primary purpose of this study was to determine the
      association of salivary and gingival crevicular fluid (GCF) cotinine levels with
      periodontal disease status in smokers and non-smokers. METHODS: 147 male smokers
      and 30 male non-smokers were included in the current longitudinal study. The 177
      individuals were part of a group of 200 subjects (89%) seen 10 years previously
      for a baseline survey. Oral hygiene indices, probing depth and attachment loss
      were recorded. Salivary and GCF cotinine levels of 58 smokers were determined by
      means of ELISA. RESULTS: Results indicated that no significant difference was
      found in subjects who smoked, when compared to subjects who did not smoke with
      respect to plaque accumulation and calculus deposits. Smokers, however, had fewer
      gingival bleeding sites. Cigarette smoking was associated with a greater increase
      in probing depth and attachment loss, as well as greater tooth loss at an earlier
      age. There was greater tooth loss in smokers than non-smokers (p < 0.001). 11
      smokers became edentulous, while only 1 non-smoker lost all his teeth within 10
      years. The degree of periodontal tissue breakdown was different in each age group
      with greater periodontal deterioration as age increased. All smokers had
      detectable salivary and GCF cotinine. Mean GCF cotinine was about 4x higher than
      mean salivary cotinine levels. Individuals who smoked > or = 20 pack years when
      compared to <20 pack years, had significantly higher saliva and GCF cotinine
      levels (p < or = 0.05). CONCLUSION: Neither salivary cotinine nor GCF cotinine
      was significantly correlated with probing depth, attachment loss and tooth loss
      (p > 0.05).

PMID- 11314890
TI  - Effects of carrier release kinetics on bone morphogenetic protein-2-induced
      periodontal regeneration in vivo.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs) have shown considerable promise as
      a therapeutic agent to enhance periodontal regeneration although the optimal
      characteristics of a suitable release system are not known. AIM: The aim of this
      study was to compare the effects of slow and fast degrading gelatin carriers on
      BMP-2-induced periodontal healing. METHOD: Recombinant human bone morphogenetic
      protein-2 (rhBMP-2) was incorporated into gelatin and subsequently differentially
      cross-linked to produce slow and fast release carrier systems. Release kinetics
      were confirmed in vitro, by measuring release of 125I-growth hormone from similar
      gelatin plugs. Effects of BMP were evaluated in surgically created rat
      periodontal fenestration defects which were processed for histology 10 days post
      operatively. The rats were divided into 4 groups and the control defects were
      treated with either slow or fast degrading gelatin (CONs or CONf respectively),
      whilst test groups were treated with 1.25 microg rhBMP-2 in the slow or fast
      degrading gelatin (BMPs or BMPf respectively). RESULTS: BMPf greatly increased
      bone formation compared with the control (CONf) (1.67 +/- 0.65 versus 0.34 +/-
      0.11 x 10(-4) m2), but no significant differences were observed with BMPs and
      CONs. In contrast, new cementum formation was significantly greater in the BMPs
      group compared with all other groups (p<0.05). CONCLUSION: Release kinetics of
      BMP may have important effects on the outcome of BMP-induced periodontal
      regeneration. New bone formation may be affected by rapid-release kinetics
      although further investigation is necessary to confirm this. In contrast, new
      cementum formation is promoted by slow release of BMP.

PMID- 11314891
TI  - Detection rate of Actinobacillus actinomycetemcomitans on the permanent 1st
      molars of primary school children in Taiwan by polymerase chain reaction.
AB  - BACKGROUND, AIMS: Actinobacillus actinomycetemcomitans (Aa) has been implicated
      as the putative micro-organism for localized juvenile periodontitis (LJP). The
      most distinct clinical features of LJP include severe angular bony defects of the
      mesial sides of permanent first molars and the onset of disease during puberty.
      Currently, no large-scale studies have been performed which address the change in
      detection rates of Aa on the mesial sides of permanent 1st molars following
      eruption and up to puberty. METHOD: In this study, subgingival plaque samples
      were taken from the mesial pockets of 2 randomly selected permanent 1st molars
      from 328 primary school children and 50 adult staff, and analyzed by polymerase
      chain reaction (PCR) to detect Aa. RESULTS: The results showed a 5.5% prevalence
      rate of Aa which increased after the eruption of 1st molars and peaked near
      puberty. There were no significant differences in the detection rates of Aa among
      different groups in terms of gender, plaque index (PII), and gingival index (GI);
      however, the higher detection rates of Aa were significantly associated with
      increased probing depths at p<0.05. CONCLUSION: PCR analysis of the subgingival
      plaques demonstrated a prevalence of Aa which peaked near puberty, suggesting
      that Aa may be important for LJP in Taiwan.

PMID- 11314892
TI  - Longitudinal evaluation of GCF MMP-3 and TIMP-1 levels as prognostic factors for
      progression of periodontitis.
AB  - BACKGROUND: To determine whether matrix metalloproteinase-3 (MMP-3) and tissue
      inhibitor of metalloproteinases-1 (TIMP-1) in gingival crevicular fluid (GCF)
      could serve as prognostic factors for the progression of periodontitis, we
      monitored GCF MMP-3 and TIMP-1 and periodontal status of selected sites in 40
      medically healthy subjects over a 6-month period. METHOD: Clinical measurements
      including gingival index (GI), plaque index, bleeding on probing, suppuration,
      probing depth (PD), attachment loss (AL), and GCF samples were taken from 2
      healthy sites (including sites with gingival recession, GI=0 PD < or =3 mm; AL <
      or =2 mm) and 2 periodontitis sites (GI > or =1; PD > or =5 mm; AL > or =3 mm) of
      each patient at baseline, 3-month and 6-month visits by means of sterile paper
      strips. GCF levels of MMP-3 and TIMP-1 were determined by sandwich ELISA assays.
      RESULTS: The mean amounts of MMP-3 and TIMP-1 in diseased sites were
      significantly higher than in healthy sites (p<0.0001). Significantly higher GCF
      levels of MMP-3 and TIMP-1 were found at progressing sites than in nonprogressing
      periodontitis sites (0.001<p<0.01). A progressing site was defined as a site
      which had > or =2 mm loss of attachment during 6- month study period. GCF levels
      of MMP-3 were highly correlated with clinical measurements taken at baseline, 3
      month and 6-month visits (p<0.001). TIMP-1 levels were only moderately correlated
      with probing depth and attachment level (p<0.01). Step-wise multiple regression
      analysis was performed to construct models for the prediction of probing depth
      and attachment loss increases. The most parsimonious regression models which had
      the best R2 values included the following variables and accounted for the
      indicated % of variability. The regression model for the prediction of probing
      depth increase included MMP-3, smoking pack-years, TIMP-1 and accounted for 53%
      of the variability. The best model for the prediction of attachment loss increase
      included MMP-3, smoking pack-years, age, TIMP-1 and explained 59% of the
      variability. CONCLUSION: These data indicate that sites with high GCF levels of
      MMP-3 and TIMP-1 are at significantly greater risk for progression of
      periodontitis.

PMID- 11314893
TI  - Toothbrush filaments end-rounding: stereomicroscope analysis.
AB  - BACKGROUND, AIMS: Toothbrush filaments with rounded ends allow for efficient
      removal of bacterial plaque and are less harmful to periodontal tissues than non
      rounded bristles. The aim of this research was to evaluate the % of rounded
      filaments considered to be of acceptable quality in different toothbrush brands
      and to determine whether there is a standardization of quality, as manufacturers
      claim. METHOD: Brushes tested included 2 samples of medium-hard nylon or tynex
      toothbrushes from 31 various types found on the retail market in Italy. Tufts
      from the same position on the toothbrush head were removed and examined under a
      stereomicroscope, utilizing methods which did not alter the physical properties
      of the filaments. In 4 of the 31 toothbrush brands tested, more than 50% of the
      filaments appeared rounded, in 19 of them, between 11.9% and 40.5% and in 8
      brands between 0% and 7%. RESULTS: Differences were found in the number and
      disposition of filaments among different brands and even within the same
      toothbrush brand. CONCLUSION: The results appear to indicate that a large % of
      toothbrushes on the retail market do not meet acceptable quality criteria.

PMID- 11314894
TI  - Pocket elimination surgery with simultaneous connective tissue graft. A case
      report with 3-year follow-up.
AB  - BACKGROUND, AIMS: The purpose of the present case report was to present 2 ways of
      treating recession in a periodontal patient combined with regular pocket
      elimination surgery. The techniques used enabled the operator to reduce the
      number of surgical sessions and clinically evaluate the 3-year coverage of
      gingival recessions using a subpedicle connective tissue graft. METHODS: Surgery
      consisted of pocket elimination procedures to treat adult periodontitis as a way
      to harvest connective tissue to be placed in the areas of recession. The grafted
      tissue was covered by the primary flap or left uncovered in a pouch, according to
      2 different techniques described in the literature. RESULTS: In this case, we
      observed that, with this approach, we were successful in reducing the number of
      surgical session as well as achieving objective and subjective goals of therapy
      in treated areas.

PMID- 11314895
TI  - Palatal radicular multigrooves associated with severe periodontal defects in
      maxillary central incisors.
AB  - BACKGROUND: This case report describes a rare condition of palatal radicular
      multigrooves on teeth 11 and 21 with severe periodontal defects and the findings
      at 3-year follow-up. METHOD: Radiculoplasty using hand curettes and rotary burs
      were used to remove the multigrooves on the root surfaces and change the wrinkled
      root form to the relatively flat and smooth normal root morphology. Minor tooth
      movement and frenotomy were performed for a diastema between teeth 11 and 21.
      Supportive periodontal therapy started immediately after completion of the active
      treatment. RESULTS: Improved healthy periodontal tissues and adequate plaque
      control have been maintained.

PMID- 11314896
TI  - Shame and non-disclosure: a study of the emotional isolation of people referred
      for psychotherapy.
AB  - Thirty-four people referred to an NHS psychotherapy department were given a
      modified form of Oatley and Duncan's (1992) emotion diary which included
      questions about whether each recorded emotion had been subsequently disclosed to
      anyone (for example a partner, friend or professional). One week later the
      diaries were collected and participants interviewed. Interviews focused, among
      other things, on reasons for nondisclosure of recorded emotional experiences and
      the relationship between shame and non-disclosure. The results indicated that a
      majority of the emotional incidents recorded in the diaries were not disclosed
      (68%). This result contrasts with studies on non-clinical samples in which only
      approximately 10% of everyday emotions are kept secret. Qualitative analysis of
      the interview data revealed that participants appeared to be habitual non
      disclosers of emotional and personal experiences and that non-disclosure was
      related to the anticipation of negative interpersonal responses to disclosure (in
      particular labelling and judging responses) in addition to more self-critical
      factors including shame. It is suggested that these results add to the existing
      literature on shame by illustrating the interpersonal effects of shame in a
      clinical sample.

PMID- 11314897
TI  - Characteristics of self-regulation in adolescent patients with anorexia nervosa.
AB  - The purpose of the study was to investigate the different modes of self
      regulation in adolescent anorexia nervosa (AN). A self-system questionnaire, the
      Narcissism Inventory, was given to 61 adolescent females with AN and 61 controls.
      Patients with AN reported higher overall disturbances in self-regulation than
      controls. In particular, a highly unstable self-system, a tendency to use
      idealization as modus of regulation, and high narcissistic gain from their
      illness was found in the patient group; however, the patients did not report a
      'classic narcissistic self'. Furthermore, we were able to differentiate between
      two clusters of patients, one with high (n = 34) and one with low (n = 27)
      disturbance in self-regulation; the latter reported a shorter duration of illness
      and lower oral control but did not differ on any other clinical variables.
      Stronger relationships were found between the dimension 'endangered self' and the
      overall scores of the Eating Attitudes Test (EAT) and the Eating Disorder
      Inventory (EDI) as well as two subscales of the EAT and five of the EDI. Our
      study in anorexic adolescents demonstrated that the self-system is experienced as
      highly unstable, that idealization is used as mode of regulation, and that the
      dimension of the 'classic narcissistic self' is less important in this patient
      group. It is important to evaluate the system of self-regulation for planning
      treatment in the individual patient according to their needs.

PMID- 11314898
TI  - The effects of solo singing, choral singing and swimming on mood and
      physiological indices.
AB  - The effects of solo singing, choral singing and swimming on mood and
      physiological indices were compared. Engaging in these activities reduced tense
      arousal and increased energetic arousal, positive hedonic tone and heart rate.
      Effects were greater for swimming than for singing, with little difference
      between choral and solo singing. Possible mechanisms and the implications for
      mental well-being are discussed.

PMID- 11314899
TI  - Cacosmia in healthy workers.
AB  - Self-reported cacosmia (i.e. feeling ill from the odour of xenobiotic substances)
      was studied in 151 young, healthy workers, unexposed to unpleasant odours and
      working in food stores without air-conditioning. Almost half (46%) of the sample
      reported feeling ill from the smell of chemical materials. Chemical odour
      intolerance induced headache, itching eyes, irritated or congested nose, dry
      and/or sore throat, cough, dizziness, and itching or rash. Cacosmic subjects
      showed a slight prevalence of the female sex, and had significantly higher
      symptom scores, anxiety, and depression than non-cacosmic subjects. Cacosmia may
      be related to multiple chemical sensitivity, sick-building syndrome and
      psychopathology. Individual variability in odour tolerance may substantially bias
      epidemiological studies on indoor air quality and health.

PMID- 11314900
TI  - Psychosis and the disintegration of dialogical self-structure: problems posed by
      schizophrenia for the maintenance of dialogue.
AB  - Researchers and theoreticians across widely varying disciplines have increasingly
      stressed how sense of self is inherently 'dialogical', or the product of ongoing
      dialogue both within the individual and between the individual and others. This
      perspective emphasizes that self-awareness is not an awareness of an isolated or
      seamless viewpoint, but a collective of numerous complementary, competing, and
      sometimes contradictory, voices. In this paper we suggest that changes in
      subjective sense of self in schizophrenia spectrum disorders may represent the
      collapse of this essential dialogue. We suggest that this collapse can have the
      end-result of mentally ill persons either coming to embrace a singular, all
      incorporating self-position or standing precariously on the brink of cacophony
      which is experienced as self-dissolution. We point to two phenomena associated
      with schizophrenia that could contribute to the derailment of internal and
      external dialogue: impairments in associative processes and affect dysregulation.
      Illustrated with a case example, we finally suggest how psychotherapy has the
      potential to revive internal dialogue through its explicit use of external
      dialogue helping to restore previous levels of social function.

PMID- 11314901
TI  - Psychopathology in paintings: a meta-analysis of studies using paintings by
      psychiatric patients.
AB  - We classified 242 reliable scales from 12 art-based studies of psychiatric
      patients into 14 qualitative categories and also by three types of decision:
      form, objective or subjective content. We used meta-analytic techniques to
      combine and compare different results from studies testing the asssociation of
      art characteristics with psychopathology. Distinctions between controls and
      patients were more apparent than those between diagnoses. The largest effects
      distinguished patients and controls on categories of content, body details,
      energy and media control. Diagnostic groups were differentiated on energy and
      complexity. There were other less distinct differences for both types of
      comparison. There were serious criticisms of the quality of the literature, and a
      lack of information on validity and reliability, but this study suggests that art
      characteristics do relate to psychopathology.

PMID- 11314902
TI  - Treating personality fragmentation and dissociation in borderline personality
      disorder: a pilot study of the impact of cognitive analytic therapy.
AB  - Recent findings suggest that personality fragmentation may be a core component of
      borderline personality disorder (BPD) and that successful treatment of BPD may
      depend on the extent to which this is addressed. Cognitive analytic therapy (CAT)
      can increase integration by strengthening awareness, and hence control, of the
      dissociative processes maintaining fragmentation. This pilot study aimed to
      conduct a systematic evaluation of the impact of CAT on BPD severity and
      personality integration. A patient series within-subject design was used. Five
      BPD participants completed a series of assessments to evaluate the impact of
      therapy on BPD severity, fragmentation, dissociation, symptomatology and
      interpersonal adjustment before, during and following 16-session CAT. By follow
      up, CAT had produced reductions in the severity of BPD for all five participants,
      and three participants showed significant changes in their levels of personality
      fragmentation. Improvements in comorbid disturbance were less consistent,
      however. Although the small number of participants involved limits these
      findings, they have theoretical and clinical interest. They generally support the
      suggestion that integration should be enhanced with BPD patients, and suggest
      that CAT may be a useful method to achieve this goal.

PMID- 11314903
TI  - Psychodynamic theory and narcissistically related personality problems: support
      from case study research.
AB  - An introductory overview of central psychodynamic theories relevant to
      narcissistically related personality problems and disorders of the self is
      provided, focusing on the central role of the child's relationship with primary
      care givers in the development of the self. A psychodynamic formulation is
      described for a 45-year-old woman experiencing depression, anxiety and despair
      following a severe rift in her previously enmeshed/merged relationship with her
      teenage daughter. The subsequent two and a half years of therapy were monitored
      using the Brief Symptom Inventory (BSI), the Dysfunctional Attitudes Scale (DAS)
      and the Object Relations Technique (ORT), producing data supportive of
      psychodynamic theory and therapy. A pattern of depression emerged during therapy
      which was in keeping with the concept of abandonment depression, as the client
      came to experience herself as more separate from her daughter and others. Changes
      in the functioning of primitive defences were also illustrated, plus the
      expression of previously denied anger, and increased abilities to be assertive,
      set limits and take care of herself.

PMID- 11314904
TI  - Psychotherapists' approaches to gay and lesbian patients/clients: a qualitative
      study.
AB  - We used qualitative research methods to examine the core issues relating to the
      approaches of psychodynamic and psychoanalytic psychotherapists to gay and
      lesbian patients and clients. The paper begins with a review of the
      psychoanalytic approaches to gay and lesbian sexuality and continues with
      material of a clinical nature, providing information about the experience of
      lesbians and gay men in psychotherapy. It also explores the attitudes of
      therapists towards gay and lesbian sexuality by discussing a range of
      psychoanalytic theories and their application to clinical work with patients and
      clients.

PMID- 11314905
TI  - Bridging the gap between attachment and object relations theories: a study of the
      transition to motherhood.
AB  - An empirical study of the relations between assessments of adult attachment
      styles and object representations was performed in the context of first-time
      mothers' emotional ties to their unborn babies. We assumed that, while
      conceptualizations of attachment behaviour and internal working models grasp the
      early basic patterns of interpersonal relationships and affect regulation, object
      representations indicate current transformations of these patterns in an
      individual's internal world. Participants were a sample of 120 women in the third
      trimester of their first pregnancy. Participants' representations of their own
      mothers were found to fully mediate the association between internal working
      models and antenatal ties to their babies. Similarities and differences between
      theoretical conceptualizations and empirical operationalizations of attachment
      and object relations theories are discussed.

PMID- 11314906
TI  - Static input-output non-linearity as the source of non-linear effects in maximum
      length sequence click-evoked OAEs.
AB  - The application of the maximum length sequence (MLS) technique to the recording
      of click-evoked otoacoustic emissions (CEOAEs) allows for a reduction in test
      time by one to two orders of magnitude. This is because the technique permits the
      use of extremely high click rates, as inter-click intervals are not constrained
      to be greater than the duration of the response. However, increasing the click
      rate also causes a progressive reduction in amplitude, or 'suppression', of the
      CEOAE. The origin of this suppression is unclear, with diverse suggestions in the
      literature as to its nature and mechanism. This paper presents a simple model of
      the well-known compressive non-linearity of the CEOAE level function, based on a
      static amplitude non-linearity within each of a number of narrowband frequency
      channels. The response of the model to MLS stimulation demonstrates suppression
      broadly of the form and magnitude previously reported in experimental studies.
      Furthermore, the model exhibits the generation of additional non-linear
      components that have been speculated on in connection with CEOAE recordings using
      the MLS technique. It is concluded that the MLS suppression phenomenon is derived
      largely, if not entirely, from the static non-linearity of the CEOAE level
      function. The approach to modelling the phenomenon as described here also bears
      promise for understanding various aspects of non-linearity in MLS-based CEOAE
      recordings.

PMID- 11314907
TI  - A study of the application of a frequency transposition hearing system in
      children.
AB  - The aim of this retrospective study was to investigate the use of the frequency
      transposition Transonic FT 40 system in a group of 36 children with profound
      sensorineural hearing loss. The group comprised 36 children (11 boys, 25 girls)
      aged between 2.8 and 15.6 years (mean 7.6 years) at fitting of the FT 40 device.
      At 48 months post-FT 40 fitting, only 11 children (30%) were still wearing the
      device. The children discontinued wearing the FT 40 for the following reasons:
      ergonomic (11%); no perceived benefit from the system (11%); cosmetic (17%); and
      subsequent cochlear implantation (30%). The performance of the long-term FT 40
      users was investigated using the following outcome measures: aided soundfield
      hearing thresholds: closed set speech tests (the E2L toy test and the Manchester
      Picture Test discrimination test) and a speech intelligibility rating score. The
      11 long-term FT 40 users (three boys, eight girls) were aged from 5.3 to 12.9
      years (mean 7.2 years) at the time of initial fitting of the FT 40 device. At
      time of fitting, the aided soundfield thresholds with the FT 40 were
      significantly better at 500 Hz (p<0.04), 1 kHz (p<0.019), 2 kHz (p<0.001) and 4
      kHz (p <0.001) compared to thresholds with conventional hearing aids. Six of 11
      children did not show any change in performance on the closed set speech tests
      and two children had intelligible speech at 48 months' follow-up. A small
      subgroup of good performers was identified. These children were younger at age of
      fitting (mean 6.2 years compared to a mean of 7.7 years for the remainder of the
      group), were predominantly oral communicators and had identified aetiologies for
      their deafness. The present study suggests that there is a small subgroup of
      hearing-impaired children who benefit from frequency transposition hearing
      systems, and future suggested fitting criteria and outcome measures are listed.

PMID- 11314908
TI  - Performance of neonatal and infant hearing screens: sensitivity and specificity.
AB  - The terms 'sensitivity' and 'specificity' are defined and some of the factors
      that determine their values are discussed in the context of screening for
      permanent childhood hearing loss. There is a need to distinguish between the
      values observed in 'simple experiments' and those that may be obtained under more
      realistic 'field' conditions. It is not feasible to give a meta-analytic overview
      of published data because of the variety of methods and objectives used in those
      studies published in the literature. However, a qualitative synthesis of the data
      is possible. This suggests that most proposed neonatal hearing screening tests,
      when implemented in accordance with a programme of quality assurance, can be
      reasonably accurate at a modest cost. However, the optimal combination of tests
      and test parameters for given populations has not yet been fully researched. The
      infant distraction test screen has a lower sensitivity than neonatal hearing
      screening tests, particularly for moderate impairments, accompanied by a fairly
      low specificity.

PMID- 11314909
TI  - Profiles of AEVs for intra- and post-operative integrity test measurements in
      young children with the Nucleus mini 22 cochlear implant.
AB  - Cochlear implantation of young children (<5 years of age) places additional
      demands on the implant team when compared to older children and adults. For these
      young children, it is essential to have integrity testing (IT) available to
      objectively assess the function of the internal device. Unfortunately, very few
      publications are available which document normal working ranges for IT. Thus the
      aim of the present study was to establish intra- and post-operative normal ranges
      for the averaged electrode voltage (AEV) which can be used in the clinical
      environment to assist in child management. As part of the routine protocol in
      Nottingham, IT was performed intra-operatively and 2 or 5 years post-operatively
      in common ground (CG) and pseudo-monopolar 1 (MP1) modes of stimulation on 30
      children. All the children were implanted with the Nucleus mini 22 device. Normal
      ranges were calculated (mean +/- 1 standard deviation (SD)) for both intra- and
      post-operative measurements. In addition, the post-operative percentage changes
      in AEV amplitude were calculated for the 2-year and 5-year data groups. Data were
      excluded from calculations if an electrode was known or suspected to be faulty by
      visual examination of the AEV profile by an experienced observer. The results
      demonstrated that the profile of the AEV across the electrode array was preserved
      between intra- and post-operative recordings, although the amplitude of all AEVs
      decreased post-operatively. The percentage decrease (mean +/- SD) in (i) CG after
      2 years was 69 (+/-16%), (ii) in CG after 5 years was 77 (+/-15%) and (iii) in
      MPI after 2 years was 35 (+/-1%). IT is a valuable objective tool to assess
      device function, in particular for young children. Normal AEV ranges are
      presented which can be used in the clinical environment to aid interpretation of
      IT performed intra- and post-operatively for CG and MP1 modes. Test data validate
      the implementation of normal ranges. Electrodes whose values of AEV amplitude
      fall outside the range should be investigated further.

PMID- 11314910
TI  - Evaluation of maximum-likelihood threshold estimation with tone-in-noise masking.
AB  - There has been much recent interest in the use of adaptive psychophysical
      procedures based on maximum-likelihood estimation (MLE) in order to minimize
      testing time. The speed and accuracy of MLE was compared to a standard
      transformed up-down algorithm in a two-interval forced-choice task. Thresholds
      for detecting a 2 kHz tone in either a broadband or a notched-noise were
      estimated in three normal-hearing listeners. The transformed up-down algorithm
      tracked 79% correct with either two, four, six or eight final turnarounds,
      whereas the MLE procedure tracked 70%, 80% or 90% correct. MLE was always
      quickest, but with a penalty in increased variability. Use of the MLE procedure
      to track 70% or 80% correct also resulted in a tendency to overestimate
      listeners' sensitivity. Reducing the number of turnarounds in the up-down
      procedure from eight to two reduced the number of trials required by nearly half
      and resulted in thresholds with similar magnitude and variability to those
      obtained using MLE to track 90% correct.

PMID- 11314911
TI  - Bisensory augmentation of complex spoken passages.
AB  - The role of the complexity of spoken passages on the magnitude of bisensory
      augmentation was investigated. The comprehension of 30 undergraduates was
      measured when listening to clearly audible but conceptually difficult auditory
      visual (AV) spoken passages, which showed an advantage over similar spoken
      passages heard alone (A), at three levels of complexity. Comprehension was
      superior in the AV relative to the A condition and the bisensory augmentation
      effect increased with linguistic complexity.

PMID- 11314912
TI  - The impact of information on maternal attitudes towards universal neonatal
      hearing screening.
AB  - In order to improve the acceptability of universal newborn hearing screening
      (UNHS) among parents, several authors have proposed that information about
      hearing screening be provided to them. The purpose of the present study was to
      test the hypothesis that mothers who are informed about their baby's hearing test
      are more likely to have a positive attitude towards hearing screening than are
      mothers who are not informed. Information given to mothers was assessed by three
      items concerning their involvement in their baby's hearing test. Subjects were 90
      mothers who were interviewed during their stay at the maternity unit after
      delivery. Mothers' attitudes towards the screening were assessed through their
      answer to the following question: 'Should UNHS be performed despite the
      possibility that parents become worried by false-positive test results?' Mothers
      who answered 'Yes' were categorized as advocates of UNHS, whereas those who
      answered 'No' or 'Undecided' were categorized as sceptics. The great majority of
      mothers (84%) turned out to be advocates. In keeping with the hypothesis, among
      advocates a significantly higher proportion of mothers were well-informed about
      the hearing test (78% versus 50%; p = 0.016), were present at the hearing test
      (51% versus 14%; p<0.01) or knew the result of the hearing test (71% versus 29%;
      p<0.01). These findings support the view that providing information about the
      hearing test will positively affect parental attitude towards UNHS.

PMID- 11314913
TI  - The effect of high-pass filtering on TEOAE in 2-month-old infants.
AB  - The aim of the present study was to investigate the effect of high-pass filtering
      on TEOAE obtained from 2-month-old infants as a function of filter cut-off
      frequency, activity states and pass/fail status of infants. Two experiments were
      performed. In Experiment 1, 100 2-month-old infants (200 ears) in five activity
      states (asleep, awake but peaceful, sucking a pacifier, feeding, restless) were
      tested by use of TEOAE technology. Five different filter conditions were applied
      to the TEOAE responses post hoc. The filter conditions were set at 781 Hz
      (default setting), 1.0, 1.2, 1.4 and 1.6 kHz. Results from this experiment showed
      that TEOAE parameters such as whole-wave reproducibility (WR) and signal-to-noise
      ratio (SNR) at 0.8 kHz and 1.6 kHz, changed as a function of the cut-off
      frequency. The findings suggest that the 1.6 kHz and 1.2 kHz filter conditions
      are optimal for WR and SNR pass/fail criteria, respectively. Although all infant
      recordings appeared to benefit from the filtering, infants in the noisy states
      seemed to benefit the most. In Experiment 2, the high-pass filtering technique
      was applied to 23 infants (35 ears) who apparently failed the TEOAE tests on
      initial screening but were subsequently awarded a pass status based on the
      results from a follow-up auditory brainstem response (ABR) assessment. The
      findings showed a significant decrease in noise contamination of the TEOAE with a
      corresponding significant increase in WR. With high-pass filtering at 1.6 kHz,
      21/35 ears could be reclassified into the pass category.

PMID- 11314914
TI  - Prediction of 8-month MEE from neonatal risk factors and test results in SCBU and
      full-term babies.
AB  - The incidence and persistence of middle ear effusion (MEE) may be affected by
      children's birth history and environment. Factors such as bottle-feeding,
      presence of parental smoking, admission to special care and a history of colds
      are all thought to increase the risk of persistent MEE. The aim of the present
      study was to determine those risk factors and neonatal test results that best
      predict presence of MEE (as measured by 220 Hz tympanometry) at 8 months of age.
      One hundred Special Care Baby Unit (SCBU) and non-SCBU babies were assessed
      neonatally and at 8 months of age with tympanometry. At each assessment, various
      risk factors were collected. Failure of 8-month tympanometry was best predicted
      by neonatal (660 Hz) tympanometry and the presence or absence of breast-feeding
      for SCBU babies. This provides further evidence that 660 Hz tympanometry may
      provide information about neonatal MEE. For non-SCBU babies the risk of failing 8
      month tympanometry was most significantly affected by a history of colds and
      parental smoking. The number of babies with each combination of risk factors in
      the present study is rather small and this has caused confidence intervals (CIs)
      to be wide and some unexpected results. However, an extended study with a larger
      and more balanced sample may facilitate accurate prediction neonatally of those
      children at risk of 8-month MEE.

PMID- 11314915
TI  - The influence of hypothermia on outer hair cells of the cochlea and its
      efferents.
AB  - Transient evoked otoacoustic emissions (TEOAE) were recorded in 21 guinea-pigs
      undergoing hypothermia. The minimal average body temperature during cooling was
      26 degrees C/24.9 degrees C measured orally or rectally, respectively. The
      animals were subsequently warmed to normal body temperature. A clear influence of
      body temperature on TEOAE could be documented. During cooling the amplitude and
      reproducibilities decreased, disappearing completely at a mean temperature below
      28.5 degrees C (oral) and 27.3 degrees C (rectal). The emissions reappeared
      during rewarming at a mean temperature of 30.1 degrees C (oral) and 30.8 degrees
      C (rectal). Contralateral auditory stimulation (CAS) led to a decrease of the
      amplitudes of TEOAE during cooling down to a mean of 33 degrees C/32 degrees C
      (oral/rectal temperature). During rewarming, influences of the CAS could be
      recognized, again at an oral temperature above 35 degrees C. The changes to the
      TEOAE observed in these experiments suggest that hypothermia affects not only the
      outer hair cells (OHC) of the cochlea but also the efferent supply to the
      cochlea.

PMID- 11314916
TI  - The human temporary threshold shift after exposure to 60 minutes' noise in an
      aerobics class.
AB  - The potential hazard of noise to hearing is well documented. However, there are
      some experiences of noise-induced hearing loss (NIHL) that are not so well-known,
      for example the effects of leisure noise, and in particular, leisure noise
      experienced during an aerobics class. A preliminary study of the noise level in
      aerobics classes in the Manchester region was carried out and their mean noise
      level was found to be 89.6 dB(A) (+/-4.7 dB(A)). Pure tone thresholds in the
      audible frequency range were obtained from 28 young adult volunteers (mean age 21
      years; standard deviation (SD) 2.3 years) and 14 subjects (the 'exposure' group)
      were then invited to join (but not participate in) an aerobics class (mean noise
      level 91.8 dB(A) (+/-1.5 dB(A)) for 60 minutes. The noise levels in the aerobics
      class were monitored throughout the 60 minutes and the subjects did not stray
      from a small marked area (2 m2). Subjects' hearing thresholds were obtained for a
      second time, beginning within 2 minutes of the cessation of the noise, and any
      temporary threshold shifts (TTS) were noted. A second group of 14 subjects (the
      control group) was invited for a second audiogram after at least 60 minutes,
      during which time subjects were not exposed to any noise. The data obtained here
      were analysed and of the 14 subjects in the exposure group all had significant
      TTS at all frequencies except 1,000 Hz. Subjects in the control group, who had
      not experienced any noise, showed significantly reduced hearing thresholds (all
      frequencies; p>0.02), showing evidence of a possible practice effect with
      audiometric testing.

PMID- 11314918
TI  - Role of spirituality in patients with sickle cell disease.
AB  - BACKGROUND: Patients with sickle cell disease cope with their disease in various
      ways, such as psychological counseling, hypnosis, medication, and prayer.
      Spirituality is a coping mechanism in a variety of diseases. This study evaluates
      the role of spirituality in patients coping with the pain of sickle cell disease.
      METHODS: Seventy-one patients from the Georgia Sickle Cell Clinic completed a
      questionnaire addressing their ability to cope with the pain of sickle cell
      disease and their degree of spirituality. A descriptive cross-sectional design
      was used. Correlation and multiple regression analyses were calculated for the
      relation between coping with the pain of sickle cell disease and spirituality.
      RESULTS: The questionnaire provided several scales with high internal consistency
      for measuring spiritual well-being and its two components, existential well-being
      and religious well-being, that show a correlation between high levels of
      spirituality and life control. The study population exhibited high levels of
      spirituality and religiosity, but the influence of these feelings on coping with
      sickle cell disease was variable. Spiritual well-being was correlated with life
      control but not with perceived pain severity. CONCLUSIONS: Existential well-being
      was associated with general coping ability. Spiritual well-being is important for
      some patients who must cope with the pain of sickle cell disease.

PMID- 11314917
TI  - Gun deaths in rural and urban settings: recommendations for prevention.
AB  - BACKGROUND: Family physicians can play a vital role in preventing gun violence,
      and better data on which to base their interventions might result in more
      effective prevention efforts. Using Washington State data, two assumptions on
      which interventions can be based were tested: compared with urban areas, rural
      areas have (1) a higher percentage of gun deaths from shotguns and rifles, and
      (2) a higher percentage of gun deaths from suicides and accidents METHODS: From
      1990 to 1996, 4,271 gun deaths on Washington death certificates were classified
      as rural or urban. The data were retrospectively sorted and analyzed by gun type
      (handguns, rifles, shotguns, or other) and by intent (suicide, homicide, or
      accidental death). RESULTS: Compared with urban settings, rural areas had a
      higher percentage of gun deaths from shotguns and rifles and a higher percentage
      from suicides and accidents (P < .01). Two similarities, however, stand out as
      more important than the confirmed hypothesized differences: handguns accounted
      for more than 50% of gun deaths, and suicides accounted for nearly 70% of gun
      deaths in both urban and rural areas. CONCLUSIONS: Family physicians might want
      to focus their firearm safety efforts on preventing handgun deaths and suicides,
      which accounted for most gun deaths in rural and urban areas. Also, data from
      this study suggest that deaths from shotguns and rifles as well as accidental and
      suicide gun deaths deserve special attention in rural areas.

PMID- 11314919
TI  - Adherence to care plan in women with abnormal Papanicolaou smears: a review of
      barriers and interventions.
AB  - BACKGROUND: Cancer of the cervix is preventable. According to the Surveillance,
      Epidemiology, and End Results (SEER) Program, invasive cervical cancer incidence
      is 9.0 and cancer mortality rate is 2.8 per 100,000 persons. Effective prevention
      includes appropriate use of Papanicolaou smears and adherence to a care plan by
      the patient. This review will examine the extent of nonadherence, negative
      outcomes, barriers, and interventions for improved adherence to care. METHODS:
      Computer searches in MEDLINE for English language articles were conducted from
      1968 to 1999 using the key words "colposcopy," "abnormal Papanicolaou smear,"
      "patient compliance," "adherence to care," and "follow-up." RESULTS: Although
      there is 10% to 40% nonadherence in the studies reviewed, the definition of
      nonadherence is not standard. Considerable morbidity from cervical cancer was
      described among nonadherent women. The most common barriers to follow-up were
      lack of understanding of the purpose of colposcopy, fear of cancer, forgetting
      appointments, and lack of time, money, or childcare. Emotional consequences of
      abnormal Papanicolaou smears had considerable impact on follow-up visits. Focused
      intervention strategies targeted to the study population were most effective in
      improving adherence. CONCLUSIONS: Nonadherence results from the interplay of
      emotional, logistic, cultural, or socioeconomic factors. Among the most effective
      strategies to improve adherence are personalized reminders to patients by their
      primary physicians and case management dictated by the size, structure, and style
      of the practice.

PMID- 11314920
TI  - Toxic shock syndrome: broadening the differential diagnosis.
AB  - BACKGROUND: Toxic shock syndrome is a rare but potentially fatal toxin-mediated
      febrile illness. Although classically associated with tampon use, it is now known
      that many nonmenstrual conditions are related to this syndrome. Serious morbidity
      and mortality can occur if this syndrome is not promptly recognized. METHODS:
      MEDLINE was searched from 1978 to the present using the phrase "toxic shock
      syndrome." Case reports and articles related to tampon-associated toxic shock
      syndrome were excluded from the literature review except when defining toxic
      shock syndrome or discussing the cause of the syndrome. A case of nonmenstrual
      toxic shock syndrome associated with an intrauterine device and a review of the
      definition, cause, diagnostic criteria, and management are reported. RESULTS AND
      CONCLUSIONS: Toxic shock syndrome can mimic many common diseases. Because it can
      be associated with a number of nonmenstrual-related conditions, patients with
      unexplained fever and rash and a toxic condition out of proportion to local
      findings should have the diagnosis of toxic shock syndrome in their differential
      diagnosis. Early recognition and aggressive management can decrease the overall
      morbidity and mortality.

PMID- 11314921
TI  - Occupational acute anaphylactic reaction to assault by perfume spray in the face.
AB  - BACKGROUND: Perfumes have been associated with rashes in employees exposed to
      scented soaps or with allergic conditions, such as rhinitis or asthma, in
      employees exposed to perfumes or fragrances in the air. METHODS: Reported here is
      a case of an anaphylactic reaction and respiratory distress as a result of a
      deliberate assault with a perfume spray. The medical literature was searched
      using the key words "fragrances," "respiratory distress," "assault," and "health
      care workers." RESULTS: A female medical assistant with no history of asthma or
      reactions to fragrances was assaulted by a patient, who pumped three sprays of a
      perfume into her face. The employee experienced an acute anaphylactic reaction
      with shortness of breath, a suffocating sensation, wheezes, and generalized
      urticaria, and required aggressive medical treatment, a long period of oral
      bronchodilator therapy, and, finally, weaning from the medications. CONCLUSIONS:
      Perfumes are complex mixtures of more than 4,000 vegetable and animal extracts
      and organic and nonorganic compounds. Fragrances have been found to cause
      exacerbations of symptoms and airway obstruction in asthmatic patients, including
      chest tightening and wheezing, and are a common cause of cosmetic allergic
      contact dermatitis. In many work settings the use of fragrances is limited.
      Assault is becoming more common among workers in the health care setting. Workers
      should be prepared to take immediate steps should an employee go into
      anaphylactic shock.

PMID- 11314922
TI  - Community-oriented primary care: critical assessment and implications for
      resident education.
AB  - BACKGROUND: Community-oriented primary care (COPC) is a systematic approach to
      health care based on principles derived from epidemiology, primary care,
      preventive medicine, and health promotion that has been shown to have positive
      health benefits for communities in the United States and worldwide. METHODS:
      MEDLINE was searched using the key phrase "community-oriented primary care."
      Other sources of information were books and other documents. RESULTS AND
      CONCLUSIONS: Because of lack of predictable reimbursement for COPC services and
      difficulties encountered incorporating COPC in medical and residency curricula,
      widespread application of COPC has not occurred. Recent trends in public health
      initiatives, managed health care, and information technology provide an
      environment ripe for application of COPC in medical practice. Also, recent
      recommendations made by the Strategic Planning Working Group of the Academic
      Family Medicine Organizations and the Association of Family Practice Residency
      Directors regarding specific community competencies for residency training have
      direct bearing on COPC and family medicine educators. These trends and
      recommendations, properly configured, will produce a medical training and
      practice environment conducive to COPC.

PMID- 11314923
TI  - Dermographism: an adverse effect of atorvastatin.

PMID- 11314924
TI  - Iguana bites to the face.

PMID- 11314925
TI  - Neonatal hypernatremic dehydration secondary to lactation failure.

PMID- 11314926
TI  - Thyroid hormone withdrawal.

PMID- 11314927
TI  - Separating zebras from horses.

PMID- 11314928
TI  - Chronic hepatitis C: common questions, practical answers.

PMID- 11314929
TI  - Postpartum weight loss and infant feeding.
AB  - BACKGROUND: Women are often advised that lactation accelerates loss of the excess
      weight gained during pregnancy, but the evidence underlying this advice is sparse
      and conflicting. To help fill this gap, we assessed differences in the rate of
      postpartum weight loss in the first 9 months postpartum according to method of
      infant feeding. METHODS: Two hundred thirty-six women attending two public health
      clinics in Montreal were weighed in one to four routine infant immunization
      visits up to the 9th postpartum month. After each weighing, we administered a
      telephone questionnaire assessing the method of infant feeding (predominantly
      breast-feeding, mixed-feeding, or predominantly bottle-feeding) and potential
      confounders. Data were analyzed using unbalanced multivariate repeated measures
      linear regression. RESULTS: Infant feeding was not associated with statistically
      significant differences in the rate of weight loss. Gestational weight gain,
      postpartum smoking, and maternal birthplace were important predictors of
      postpartum weight change. CONCLUSION: Although our results cannot exclude an
      effect of more exclusive or more prolonged breast-feeding, breast-feeding as
      commonly practiced does not appear to influence the rate of postpartum weight
      loss. This information should be useful in counseling new or prospective mothers
      and in avoiding unrealistic expectations.

PMID- 11314931
TI  - The "true" sentinel lymph node: in search of an operational definition of a
      biological phenomenon.

PMID- 11314930
TI  - A two-item conjoint screen for alcohol and other drug problems.
AB  - BACKGROUND: Although nonmedical use of illicit and prescription drugs is not
      uncommon among American adults, the currently recommended screens for substance
      use disorders focus only on alcohol. This study reports on the criterion validity
      of a two-item conjoint screen (TICS) for alcohol and other drug abuse or
      dependence for a split sample of primary care patients. METHODS: Two random
      samples of primary care patients aged 18 to 59 years responded to several
      screening items that emanated from a focus group process. The DSM-III-R criteria
      for substance use disorders, as codified by the Composite International
      Diagnostic Interview-Substance Abuse Module, served as the criterion standard.
      RESULTS: At least one positive response to the TICS (In the last year, have you
      ever drunk or used drugs more than you meant to? and Have you felt you wanted or
      needed to cut down on your drinking or drug use in the last year?) detected
      current substance use disorders with nearly 80% sensitivity and specificity. The
      TICS was particularly sensitive to polysubstance use disorders. Respondents who
      gave 0, 1, and 2 positive responses had a 7.3%, 36.5%, and 72.4% chance of a
      current substance use disorder, respectively; likelihood ratios were 0.27, 1.93,
      and 8.77. The results were consistent across split samples of 434 and 702
      participants. CONCLUSIONS: Current alcohol or other drug problems can be detected
      in nearly 80% of young and middle-aged patients by asking two questions that are
      easily integrated into a clinical interview.

PMID- 11314932
TI  - Surrogate markers of effective anti-tumor immunity.

PMID- 11314933
TI  - Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be
      removed?
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of
      staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is
      performed by intradermal injection of a vital blue dye (isosulfan blue) plus
      radioactive colloid (technetium sulfur colloid) around the site of the tumor.
      Intraoperative gamma probe detection has been shown to improve the rate of SLN
      identification compared to the use of blue dye alone. However, multiple sentinel
      nodes often are detected using the gamma probe. It is not clear whether these
      additional lymph nodes represent true sentinel nodes, or second-echelon lymph
      nodes that have received radiocolloid particles that have passed through the true
      sentinel node. This analysis was performed to determine the frequency with which
      these less radioactive lymph nodes contain metastatic disease when the most
      radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt
      Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm
      or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was
      performed by injection of technetium sulfur colloid plus isosulfan blue dye in
      99% of cases. Intraoperative determination of the degree of radioactivity of
      sentinel nodes (ex vivo) was measured, as well as the degree of blue dye
      staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184
      patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel
      node metastases detected by histology or immunohistochemistry. Nodal metastases
      were detected in 306 nodal basins in these 288 patients. There were 175 nodal
      basins from 170 patients in which at least one positive sentinel node was found
      and more than one sentinel node was harvested. Blue dye staining was found in
      86.3% of the histologically positive sentinel nodes and 66.4% of the negative
      sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive
      sentinel node was negative for tumor when another, less radioactive, sentinel
      node was positive for tumor. In 20 of 40 cases (50%), the less radioactive
      positive sentinel node contained 50% or less of the radioactive count of the
      hottest lymph node. The cervical lymph node basin was associated with an
      increased likelihood of finding a positive sentinel node other than the hottest
      node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had
      been removed, 13.1% of the nodal basins with positive sentinel nodes would have
      been missed. It is recommended that all blue lymph nodes and all nodes that
      measure 10% or higher of the ex vivo radioactive count of the hottest sentinel
      node should be harvested for optimal detection of nodal metastases.

PMID- 11314934
TI  - Serum TA90 antigen-antibody complex as a surrogate marker for the efficacy of a
      polyvalent allogeneic whole-cell vaccine (CancerVax) in melanoma.
AB  - INTRODUCTION: TA90 is a tumor-associated 90-kD glycoprotein antigen expressed on
      most melanoma cells, including those of CancerVax, a polyvalent allogeneic whole
      cell vaccine. Previous studies have shown that a TA90 antigen-antibody immune
      complex (IC) in the serum of patients with melanoma is a marker of subclinical
      tumor burden and a strong prognostic factor. We hypothesized that the induction
      of TA90-IC during postoperative adjuvant CancerVax therapy might indicate vaccine
      mediated immune destruction of subclinical melanoma cells with release of TA90,
      and thereby serve as a surrogate marker of vaccine efficacy. METHODS: From 1993
      to 1997, 219 melanoma patients were enrolled in a prospective phase II trial of
      CancerVax plus bacille Calmette-Guerin (BCG) after complete tumor resection.
      Coded serum samples were prospectively collected and analyzed for TA90-IC before
      and 2, 4, 8, 12, and 16 weeks after initiation of CancerVax therapy. TA90-IC
      seroconverters were those patients whose negative TA90-IC values (< .410) became
      positive (> or = .410) after initiation of CancerVax treatment. RESULTS: Before
      CancerVax therapy, 51 patients had positive TA90-IC values and 168 patients had
      negative TA90-IC values. During CancerVax treatment, all 51 positive patients
      remained positive, 79 (47%) negative patients seroconverted to positive, and 89
      (53%) negative patients remained negative. Seroconverters had higher 2-year rates
      of disease-free survival (59% vs. 32%; P < .006) and overall survival (78% vs.
      63%; P < .02) than did patients whose TA90-IC values remained positive.
      CONCLUSIONS: CancerVax induces TA90-IC in melanoma patients with subclinical
      disease. TA90-IC seroconverted patients have significantly improved disease-free
      and overall survival compared with TA90-IC positive patients. TA90-IC is an
      important prognostic factor that can serve as a surrogate marker for the clinical
      efficacy of CancerVax.

PMID- 11314935
TI  - Multimodality treatment of Merkel cell carcinoma: case series and literature
      review of 1024 cases.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an unusual and potentially aggressive
      cancer of the skin. There is no consensus regarding the optimal therapeutic
      approach, and the relative roles of surgery, radiotherapy, and chemotherapy still
      are controversial The aim of this study is to analyze the roles of these
      therapeutic options. METHODS: The medical records of 16 patients with a diagnosis
      of localized, primary MCC treated at the University of Alabama at Birmingham were
      reviewed. An extensive review of the English-language literature also was
      performed. The Kaplan-Meier method was used to develop the survival curves.
      Comparisons were made using Fisher's exact test. Significance was defined as P <
      .05. RESULTS: MCC presented primarily in Caucasians (98.3%) with a median age of
      69 years. Immunosuppressive therapy appeared to play a role in the development of
      this cancer. In the UAB experience, 3-year actuarial survival was 31%. The only
      factor significantly associated with overall survival was the stage of disease at
      presentation: median survivals were 97 vs. 15 months for stages I and II,
      respectively (log-rank, P = .02). From the literature review, adjuvant
      radiotherapy was associated with a reduced risk of local recurrence (P < .00001).
      CONCLUSIONS: MCC is an aggressive cancer, with a high tendency for local
      recurrence and distant spread. Surgery and adjuvant radiotherapy appear to
      provide optimal local control. The role of chemotherapy remains to be defined.

PMID- 11314936
TI  - The value of Cloquet's node in predicting melanoma nodal metastases in the pelvic
      lymph node basin.
AB  - BACKGROUND: A selection of melanoma patients with groin metastases can benefit
      from a pelvic (iliac/obturator) lymph node dissection in addition to the
      infrainguinal dissection. However, there are no reliable criteria to determine
      which patients may benefit from such an inguinal-pelvic lymphadenectomy. METHODS:
      In 142 patients (group A) out of a review of 214 groin dissections performed
      between 1980 and 1994, the tumor status of Cloquet's node was traced
      retrospectively. In 52 additional patients (group B), the status of Cloquet's
      node was registered prospectively. The number of positive lymph nodes and the
      total numbers of retrieved nodes were recorded as well. All patients underwent a
      combined therapeutic inguinal-pelvic lymph node dissection between January 1995
      and June 1999 in a tertiary referral center. RESULTS: Cloquet's node was free of
      disease in 18 of 39 patients with involved pelvic nodes in the retrospective
      study (sensitivity, 54%; negative predictive value, 83%). In the prospective
      study, 9 of the 20 patients with involved pelvic nodes had a tumor-free Cloquet's
      node (sensitivity, 55%; negative predictive value, 78%). Additional
      immunohistochemical staining of Cloquet's node resulted in a sensitivity of 65%.
      In the combined group A&B, the number of positive nodes in the inguinal region
      (cutoff point more than three nodes) had a sensitivity of 41% and a negative
      predictive value of 78% to determine the pelvic nodal status. When we combined
      the number of positive inguinal nodes and Cloquet's node in group A&B, the best
      sensitivity was 56% and the best negative predictive value was 82%. CONCLUSIONS:
      Cloquet's node has a low sensitivity to predict the pelvic nodal tumor status.
      This was barely improved when we accounted for the number of positive inguinal
      nodes. Groin lymph node dissections should encompass the iliac and obturator
      compartments in patients with palpable inguinal node metastases.

PMID- 11314937
TI  - Analysis of the survival period in resectable stage IV gastric cancer.
AB  - BACKGROUND: Patients with stage IV gastric cancer usually have a poor prognosis,
      but some patients with resectable cancer survive for more than 5 years. We aimed
      to study the correlation of protein expression and survival in resectable stage
      IV gastric cancer. PATIENTS AND METHODS: Tissue samples of 42 patients with
      resectable stage IV gastric cancer were stained immunohistochemically for the
      mutant p53 protein and heat shock protein-27 (hsp27). The correlation between
      protein expression and clinicopathological factors was investigated. Furthermore,
      prognostic value of each factor was analyzed. RESULTS: Univariate analysis showed
      that pN factors (Japanese classification, P = .028; International Union Against
      Cancer classification, P = .024), blood vessel invasion (P = .043), hsp27
      overexpression (P = .019), and the index of p53 and hsp27 overexpression (P =
      .0026) had a prognostic influence. Only Lauren classification, however, revealed
      the prognostic influence in multivariate analysis (P = .046). CONCLUSIONS: These
      results suggest that immunostaining of tumor specimens for p53 and hsp27 and
      clinicopathological analysis may help predict the survival of patients with
      resectable stage IV gastric cancer.

PMID- 11314938
TI  - Frozen section investigation of the sentinel node in malignant melanoma and
      breast cancer.
AB  - BACKGROUND: Intraoperative frozen section investigation allows immediate regional
      lymph node dissection when the sentinel node contains tumor. The purpose of this
      study was to determine the sensitivity of frozen section diagnosis of the
      sentinel node in melanoma and breast cancer patients. METHODS: A total of 177
      sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast
      cancer patients were assessed by frozen section investigation. Nodes were
      bisected, and a complete cross-section was obtained for frozen section. Step
      sections at three levels were made of the remaining lymphatic tissue and were
      stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast
      cancer) to obtain a final pathological diagnosis. RESULTS: Frozen section
      investigation revealed metastases in 8 of 17 node-positive melanoma patients
      (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases
      were identified with frozen section. The specificity was 100% and 99%,
      respectively. CONCLUSION: The sensitivity of intraoperative frozen section
      investigation of sentinel nodes was 47% in melanoma patients and 74% in breast
      cancer patients. Frozen section examination allows immediate axillary lymph node
      dissection in the majority of node-positive breast cancer patients. Frozen
      section analysis is not recommended in patients with melanoma.

PMID- 11314939
TI  - Treatment of metastatic breast cancer with somatostatin analogues--a meta
      analysis.
AB  - BACKGROUND: Somatostatin analogues appear to have antiproliferative effects in
      breast cancer by inhibiting various hormones. Several small phase 1 and 2
      clinical trails have evaluated the efficacy of somatostatin analogues, but the
      results are varied. The purpose of this study was to use the technique of meta
      analysis to determine the effect of somatostatin analogues on tumor response,
      toxicity, and serum hormone levels in women with metastatic breast cancer.
      METHODS: All published and unpublished trials were reviewed. Meta-analysis was
      preformed by best linear unbiased estimate regression with observations weighted
      inversely to their variance. Significance was considered at P < .05. RESULTS:
      Fourteen studies (N = 210) were included. Positive tumor response was reported in
      87 patients (41.4%). Mean duration of response was 3.9 months. Response was best
      when somatostatin analogues were given as first-line therapy (69.5% versus 28.5%,
      P < .006) and in patients with < or =2 metastases (45.0% versus 5.6%, P = .3).
      Mild side effects occurred in 47 of 185 patients (25.4%). Therapy was associated
      with a decrease in serum insulin-like growth factor (IGF-1) and an increase in
      growth hormone. CONCLUSIONS: In patients with metastatic breast cancer, treatment
      with somatostatin analogues was associated with a tumor response of over 40% with
      few side effects. Best results were achieved when somatostatin analogues were
      given as first-line therapy.

PMID- 11314940
TI  - Internal mammary lymph node drainage patterns in patients with breast cancer
      documented by breast lymphoscintigraphy.
AB  - BACKGROUND: Metastases to internal mammary lymph nodes (IMN) may occur in
      patients with breast cancer and may alter treatment recommendations. The purpose
      of this study was to identify the frequency of IMN drainage in patients
      undergoing breast lymphoscintigraphy and sentinel lymph node dissection (SLND).
      METHODS: The combined technique of peritumoral injection of radiocolloid and
      Lymphazurin blue for SLND was performed on 220 patients. All patients underwent
      preoperative lymphoscintigraphy before SLND. Lesion location by quadrant
      included: 110 upper outer (UOQ), 49 lower outer (LOQ), 30 upper inner (UIQ), 24
      lower inner (LIQ), and 7 central. RESULTS: Drainage to any nodal basin was
      observed in 184 of 220 patients (84%). IMN drainage was documented in 37 of 220
      (17%) of patients. IMN drainage without evidence of axillary drainage occurred in
      2 of 220 patients(1%). Drainage to the IMN based on quadrant location of the
      lesion was as follows: UOQ, 10%; LOQ, 27%; UIQ, 17%; LIQ, 25%; and central, 29%.
      CONCLUSIONS: Internal mammary lymph node drainage shown by breast
      lymphoscintigraphy is common. Tumors in all quadrants may drain to IMNs, although
      drainage is significantly more common from quadrants other than the UOQ. Further
      studies are needed to determine whether lymphoscintigraphy drainage patterns
      identify patients at the highest risk for IMN metastases who may benefit from
      radiotherapy.

PMID- 11314941
TI  - Dermal versus intraparenchymal lymphoscintigraphy of the breast.
AB  - BACKGROUND AND OBJECTIVE: Dermal and intraparenchymal (IP) injections of
      radiocolloid have been used for lymphoscintigraphic identification of the
      sentinel node (SN) in breast cancer. Because of our institute's extensive
      experience with dermal and IP lymphoscintigraphy for melanoma and breast cancer,
      we compared patterns of lymphatic migration after both types of injections to
      identify any differences in drainage patterns or SN identification. METHODS:
      Lymphoscintigrams (n = 31) after dermal injections in 30 patients with primary
      cutaneous melanoma on the breast were compared with lymphoscintigrams after IP
      injections in 97 consecutive patients with breast cancer. In each case, 400
      microCi of filtered 99mTc-sulfur colloid was injected in four quadrants around
      the tumor or in the biopsy cavity. All lymphoscintigrams were reviewed for
      patterns of migration and SN location. RESULTS: Five of 31 (16%) dermal
      injections demonstrated bilateral axillary migration (n = 3) or a suprasternal SN
      (n = 2), neither of which was found with IP injections. Conversely, 3 of 97 (3%)
      IP injections demonstrated direct supraclavicular (n = 2) or costal margin (n =
      1) nodes (P = .006), neither of which was found with dermal injections. Low
      axillary SNs were noted after 26 (84%) dermal and 93 (96%) IP injections (P =
      .037). The incidence of extra-axillary SNs was 26% (8 of 31) in the dermal group
      but only 5% (5 of 97) in the IP group (P = .0027). CONCLUSION: There is a
      significant difference in lymphatic drainage and SN localization between dermal
      and IP lymphoscintigraphy. This finding has implications for injection techniques
      when lymphatic mapping of the SN is undertaken to stage a breast carcinoma.

PMID- 11314942
TI  - Laparoscopy predicts metastatic disease and spares laparotomy in selected
      patients with pancreatic nonfunctioning islet cell tumors.
AB  - INTRODUCTION: Our objective was to compare the efficacy of CT alone to CT
      followed by laparoscopy in determining resectability of pancreatic nonfunctioning
      islet (NFI) cell tumors. METHODS: A retrospective analysis from 1993 to 1999
      revealed 48 patients who underwent surgical evaluation for NFI cell tumors. Of
      these, 34 (71%) patients underwent laparoscopy and CT for either diagnostic
      purposes or tumor staging. CT and laparoscopic criteria for curative
      resectability were defined and the sensitivity, specificity, and predictive value
      of both modalities in determining resectability were calculated. RESULTS: The
      most frequent tumor location and presenting symptoms were pancreatic head (n =
      27, 56%) and abdominal pain (n = 31, 65%), respectively. Median tumor size was
      4.0 cm. In the laparoscopy group, curative resection was performed in 20 cases
      (59%). CT followed by laparoscopy was more sensitive than CT alone in predicting
      resectability (93% vs. 50%, P = 0.03) with similar specificity (both 100%). The
      predictive value for tumor resectability was 74% for CT alone and 95% for CT
      followed by laparoscopy. Reasons for unresectability identified at laparoscopy
      but not indicated by CT were liver metastases (n = 6) or nodal disease (n = 1).
      Four of these patients were spared a laparotomy while the other three patients
      underwent surgical palliation and all are alive with disease (AWD). In those not
      undergoing laparoscopy (n = 14), curative resection was performed in 64% (n = 9).
      Four of these patients underwent resection, despite having metastases, and three
      are AWD. CONCLUSIONS: NFI cell tumors of the pancreas present as large masses
      with frequent metastases. Despite metastatic disease, prolonged survival is often
      achieved with or without open surgical treatment. Laparoscopy can be used in
      diagnosis and accurately identifies metastases not seen on CT, thus sparing
      laparotomy in some patients.

PMID- 11314943
TI  - Preliminary report of photodynamic therapy for intraperitoneal sarcomatosis.
AB  - INTRODUCTION: Sarcomatosis is the disseminated intraperitoneal spread of sarcoma.
      It is a condition for which there is no effective treatment. Photodynamic therapy
      (PDT) is a cancer treatment modality that uses a photosensitizing agent and laser
      light to kill cells. We report our preliminary Phase II clinical trial experience
      using PDT for the treatment of intraperitoneal sarcomatosis. METHODS: From May
      1997 to December 1998 eleven patients received twelve PDT treatments for
      intraperitoneal sarcomatosis. Photofrin (PF) 2.5 mg/kg was administered
      intravenously 48 hours before surgical debulking to a maximum residual tumor size
      of less than 5 mm. Light therapy was administered at a fluence of 2.5 J/cm2 of
      532 nm green light to the mesentery and serosa of the small bowel and colon; 5
      J/cm2 of 630 nm red light to the stomach and duodenum; 7.5 J/cm2 of red light to
      the surface of the liver, spleen, and diaphragms; and 10 J/cm2 of red light to
      the retroperitoneal gutters and pelvis. Light fluence was measured with an on
      line light dosimetry system. Response to treatment was evaluated by abdominal CT
      scan at 3 and 6 months, diagnostic laparoscopy at 3 to 6 months, and clinical
      examination every 3 months. RESULTS: Adequate tumor debulking required an
      omentectomy in eight patients (73%), small bowel resection in seven patients
      (64%), colon resection in four patients (36%), splenectomy in one patient (9%),
      and a left spermatic cord resection in one patient. Five patients (45%) have no
      evidence of disease at follow-up (range, 1.7-17.3 months), including patients at
      13.8 and 17.3 months examined by CT. Two patients (18%) died from disease
      progression. Four patients (36%) are alive with disease progression. Toxicities
      related to PDT included substantial postoperative fluid shifts with volume
      overload, transient thrombocytopenia, and elevated liver function tests. One
      patient suffered a postoperative pulmonary embolism complicated by adult
      respiratory distress syndrome (ARDS). CONCLUSIONS: Debulking surgery with
      intraperitoneal PDT for sarcomatosis is feasible. Preliminary response data
      suggest prolonged relapse-free survival in some patients. Additional follow-up
      with more patients will be necessary for full evaluation of the added benefit of
      PDT and aggressive surgical debulking in these patients.

PMID- 11314944
TI  - Vascular endothelial growth factor and soft tissue sarcomas: tumor expression
      correlates with grade.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF), an endothelial-specific
      mitogen overexpressed in various epithelial malignancies is thought to be a
      potent regulator of angiogenesis. We hypothesized that some soft tissue sarcomas,
      due to their high propensity for hematogenous metastases (1) would overexpress
      VEGF, (2) that the degree of expression may represent a significant biologic
      predictor for disease-specific survival, and (3) that recurrent tumor would
      express as high or higher VEGF compared with the primary tumor. METHODS: Selected
      paraffin-embedded tissue of surgical specimens from 79 patients with soft tissue
      sarcomas, treated between 1989 and 1995 were stained with a rabbit polyclonal
      anti-VEGF antibody at a concentration of 2 microg/ml. Slides were assessed for
      VEGF expression as high or low by two investigators blinded to the
      clinicopathologic data. Twelve patients had VEGF expression of their primary
      tumors, and their recurrent tumors were compared. The Fishers' exact test
      assessed for differences in VEGF expression; survival analyses were performed
      according to the methods of Kaplan and Meier. RESULTS: Seventy-eight percent (29
      of 37) of patients who died of disease had high VEGF expression. However, VEGF
      expression was not an independent predictor of either overall or disease-free
      survival. Tumor grade correlated with VEGF expression significantly. For the low
      grade tumors, 7 of 13 expressed low VEGF, whereas for high-grade tumors, 53 of 66
      expressed high VEGF (P = .016). Seven of the 12 paired tumor samples expressed
      identical VEGF immunostaining. CONCLUSIONS: The majority of high-grade soft
      tissue sarcomas in this study have high intensity VEGF expression. This finding
      may provide useful information on individual soft tissue sarcomas and offer the
      basis for therapeutic and biologic targeting in high-risk patients using anti
      angiogenesis strategies. However, in our analysis, after accounting for tumor
      grade, VEGF does not seem to be an independent predictor of clinical outcome.

PMID- 11314945
TI  - Blue dye for sentinel lymph node mapping: not too sensitive, but too
      hypersensitive?

PMID- 11314946
TI  - Comment on the article "Distant soft tissue metastases: a series of 30 new
      patients and 91 cases from the literature," by Damron and Heiner, August, 2000,
      Annals of Surgical Oncology.

PMID- 11314947
TI  - A response to Lee M. Ellis's editorial: A perspective on sentinel lymph node
      biopsy in colorectal cancer: the race between surgical technology and molecular
      oncology.

PMID- 11314948
TI  - Agmatine deiminase from maize shoots: purification and properties.
AB  - Agmatine deiminase was purified to a specific activity of 537 nkat/mg protein
      using an improved procedure. The recovery was 47% and the enzyme was homogeneous
      and remarkably stable. The molecular mass of the enzyme as determined by gel
      filtration was 75 kDa, and SDS-PAGE suggests that the enzyme is a heterodimer
      composed of subunits of 43.5 and 44 kDa. The Km for agmatine was 12 microM and
      arcaine was shown to be a potent competitive inhibitor of the enzyme, with a Ki
      of 3.3 microM. The enzyme does not have either putrescine synthase activity or
      the activities of its components ornithine and putrescine transcarbamylase. These
      results distinctly demonstrate that agmatine deiminase is different from
      putrescine synthase.

PMID- 11314949
TI  - Purification and characterization of coclaurine N-methyltransferase from cultured
      Coptis japonica cells.
AB  - S-Adenosyl-L-methionine (SAM): coclaurine N-methyltransferase (CNMT), which
      catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the
      amino group of the tetrahydrobenzylisoquinoline alkaloid coclaurine. was purified
      340-fold from Coptis japonica cells in 1% yield to give an almost homogeneous
      protein. The purified enzyme, which occurred as a homotetramer with a native Mr
      of 160 kDa (gel-filtration chromatography) and a subunit Mr of 45 kDa (SDS
      polyacrylamide gel electrophoresis), had an optimum pH of 7.0 and a pI of 4.2.
      Whereas (R)-coclaurine was the best substrate for enzyme activity, Coptis CNMT
      had broad substrate specificity and no stereospecificity CNMT methylated
      norlaudanosoline, 6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline and 1-methyl-6,7
      dihydroxy-1,2,3,4-tetrahydroisoquinoline. The enzyme did not require any metal
      ion. p-Chloromercuribenzoate and iodoacetamide did not inhibit CNMT activity, but
      the addition of Co2+, Cu2+ or Mn2+ at 5 mM severely inhibited such activity by
      75, 47 and 57%, respectively. The substrate-saturation kinetics of CNMT for
      norreticuline and SAM were of the typical Michaelis-Menten-type with respective
      Km values of 0.38 and 0.65 mM.

PMID- 11314950
TI  - Identification of phytochelatin-related peptides in maize seedlings exposed to
      cadmium and obtained enzymatically in vitro.
AB  - An analytical strategy based on the sensitivity of electrospray tandem mass
      spectrometry following a simplified and reproducible sample preparation procedure
      was evaluated for the determination of Cd-induced phytochelatins (PC) and related
      peptides in four maize varieties. In addition to the three known families of PC
      (PC, desGly-PC and iso-PC(Glu)) that were observed, novel PC and desGly-PC
      homologues lacking the N-terminal gamma-linked Glu were isolated from maize root
      extracts for the first time. Additionally the complete sequence of iso-PC3(Glu)
      was determined by tandem mass spectrometry. Peptides obtained in vivo and in
      vitro as the result of the reaction of glutathione with the enzyme phytochelatin
      synthase were compared. Minor forms detected from in vitro reactions include
      compounds with intramolecular or intermolecular disulfide bonds resulting from
      the oxidation of SH groups, phytochelatin homologues lacking the N-terminal gamma
      linked Glu, and new PC-related peptides with a Cys-Cys motif. Since peptides
      lacking a gammaGlu residue could be generated as artifacts in electrospray mass
      spectrometry, the application of capillary electrophoresis with online
      electrospray mass spectrometry allowed the separation and detection of such
      peptides as endogenous molecules present in planta and as products of in vitro
      reactions.

PMID- 11314952
TI  - Visible light-dependent degradation of long-chain alkenes in killed cells of
      Emiliania huxleyi and Nannochloropsis salina.
AB  - Photosensitized degradation rates of phytoplanktonic n-alkenes under visible
      light exposure were determined in laboratory experiments. Killed cells of
      Emiliania huxleyi and Nannochloropsis salina were used as source of biogenic
      alkenes. In E. huxleyi killed cells, minor C31 and C33 n-alkenes were strongly
      photodegraded, while the major C37 and C38 n-alkenes appeared particularly
      recalcitrant towards photochemical processes. This particular photochemical
      recalcitrance has been attributed to the chemical structure and localization of
      these hydrocarbons in the cells. Most of the n-alkenes of N. salina were strongly
      photodegraded in killed cells. The photodegradation of phytoplanktonic alkenes
      showed apparent second-order kinetics with respect to light exposure, and the
      half-life doses obtained logically decrease with increasing number of double
      bonds in these compounds. These results strongly suggest that significant amounts
      of phytoplanktonic n-alkenes must be photodegraded in the euphotic zone of the
      oceans during senescence.

PMID- 11314951
TI  - Induced accumulation of 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside
      (HDMBOA-Glc) in maize leaves.
AB  - Accumulation of 2-(2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one)-beta-D
      glucopyranose (HDMBOA-Glc) was induced in maize leaves by treatment with CuCl2,
      chitopentaose, penta-N-acetylchitopentaose, or jasmonic acid (JA). The
      accumulation of HDMBOA-Glc was accompanied by a decrease in level of 2-(2,4
      dihydroxy-7-methoxy-1,4-benzoxazin-3-one)-beta-D-glucopyranose (DIMBOA-Glc). When
      the leaf segments were treated with JA in the presence of [Me-2H3]L-methionine,
      the label was efficiently incorporated into HDMBOA-Glc, while no incorporation
      into DIMBOA-Glc or HMBOA-Glc was detected, suggesting the conversion of
      constitutive DIMBOA-Glc to HDMBOA-Glc by methylation at the 4-position. Levels of
      endogenous JA and its leucine conjugate transiently increased prior to the
      accumulation of HDMBOA-Glc in leaf segments treated with CuCl2 and chitopentaose.
      The lipoxygenase inhibitor ibuprofen suppressed the accumulation of HDMBOA-Glc
      induced by CuCl2 treatment, and the reduced accumulation of HDMBOA-Glc was
      recovered by addition of JA. These findings suggested that JA functions as a
      signal transducer in the induction of HDMBOA-Glc accumulation.

PMID- 11314953
TI  - Silicon and heavy metal tolerance of higher plants.
AB  - The heavy metal tolerant Cardaminopsis halleri, grown on Zn and Cu polluted soil,
      showed electron dense metal containing precipitates (Zn, Cu, Sn, Fe, Al) on the
      leaf surface, in the intercellular spaces (Zn, Cu, Sn), the cell walls and the
      cell wall thickenings of the xylem vessels (Zn, traces of Cu and Fe). Large
      amounts of Zn were measured in the vacuoles, the main storage compartment for
      this metal in Cardarminopsis. The cytoplasm and nuclei contained small
      precipitates, including mainly Zn and Si. As shown by ESI Zn was co-localized
      with Si in these structures. The EEL-spectra of the cytoplasmic precipitates
      corresponded with the spectra of Zn-silicate. Besides Zn-silicate, electron
      translucent structures in the cytoplasm were identified as SiO2 by their EEL
      spectra. It was concluded that in the cytoplasm of Cardaminopsis Zn is
      transiently accumulated as silicate, being slowly degraded to SiO2. Zn is
      translocated into the vacuole and accumulated in an unknown form. A second Si and
      Zn-uptake mechanism was found, excluding a membrane and cytoplasm passage.
      Pinocytotic vesicles, formed by the plasmamembrane and the tonoplast, enable a
      direct translocation of Si and Zn from extracellular compartments into the
      vacuole. The formation of Zn-silicate is part of the heavy metal tolerance
      mechanism and may be responsible for the amelioration of the Zn toxicity in
      Cardaminopsis.

PMID- 11314954
TI  - Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona
      collinsae.
AB  - The occurrence of two alkaloids, 16,17-didehydro-16(E)-stemofoline and its isomer
      at C-4, 16,17-didehydro-4(E)-16(E)-stemofoline, were found together with a known
      insecticidal compound, stemofoline, in Stemona collinsae. The 16,17-didehydro
      16(E)-stemofoline displayed higher insecticidal and antifeedant activities
      against the diamondback moth larvae than stemofoline.

PMID- 11314955
TI  - Sequestration of phenanthroindolizidine alkaloids by an Asclepiadaceae-feeding
      danaid butterfly, Ideopsis similis.
AB  - 3-Demethyl-14alpha-hydroxyisotylocrebrine N-oxide was isolated along with three
      homologous isotylocrebrine type alkaloids from the imagines and pupae of Ideopsis
      similis reared on the host plant, Tylophora tanakae.

PMID- 11314956
TI  - Fragrance volatiles of developing and senescing carnation flowers.
AB  - Thirteen major volatiles of the carnation flower fragrance signature have been
      identified by GC/MS. Of these, ten, hexanal, (2E)-hexenal, 1-hexanol, 2-hexanol,
      3-hexen-1-ol, nonanal, benzaldehyde, benzyl alcohol, benzyl benzoate and
      caryophyllene, were quantified. The steady-state levels of these ten volatiles
      change independently as the flowers develop and senesce, suggesting that their
      synthesis is developmentally regulated. In addition, the chemical composition of
      the fragrance signature in naturally senesced flowers proved to be very different
      from that for flowers that had been induced to senesce prematurely by treatment
      with ethylene. Thus, senescence-related changes in carnation floral scent appear
      not to be directly regulated by ethylene. From cellular fractionation studies, it
      is evident that all of the volatiles, except 2-hexanol, are present in both
      membranous and cytosolic compartments, suggesting that their synthesis is
      membrane-associated and that they subsequently partition into the cytosol in
      accordance with partition coefficients.

PMID- 11314957
TI  - Anthocyanins from the scarlet flowers of Anemone coronaria.
AB  - Three acylated anthocyanins were isolated from the scarlet flowers of Anemone
      coronaria 'St. Brigid Red' along with a known pigment, pelargonidin 3
      lathyroside. The structures of the acylated pigments were based on a pelargonidin
      3-lathyroside skeleton acylated at different positions with malonic acid. The
      first pigment was identified as pelargonidin 3-O-[2-(beta-D-xylopyranosyl)-6-O
      (malonyl)-beta-D-galactopyranoside], the second was pelargonidin 3-O-[2-O-(beta-D
      xylopyranosyl)-6-O-(methyl-malonyl)-beta-D-galactopyranoside], and the third was
      (6''-O-(pelargonidin 3-O-[2''-O-(beta-D-xylopyranosyl)-beta-D
      galactopyranosyl]))((4-O-(beta-D-glucopyranosyl)-trans-caffeoyl)-O
      tartatryl)malonate.

PMID- 11314958
TI  - Kaempferide triglycoside: a possible factor of resistance of carnation (Dianthus
      caryophyllus) to Fusarium oxysporum f. sp. dianthi.
AB  - A kaempferide triglycoside has been found as a constitutive component in an
      uninfected carnation (Dianthus caryophyllus) of the cultivar Novada. The chemical
      structure has been determined mainly by the use of spectroscopic methods,
      including 2D NMR experiments. It showed a strong activity in restricting fungal
      parasite development, which could contribute to the known ability of carnation
      cv. Novada to resist to Fusarium oxysporum f. sp. dianthi infection.

PMID- 11314959
TI  - Bioactive constituents from gum guggul (Commiphora wightii).
AB  - Bioactivity-directed fractionation and purification afforded cytotoxic components
      of Commiphora wightii. The exudates of C. wightii were extracted with EtOAc and
      the extract was subjected to repeated column chromatography. A fraction showing
      cytotoxic activity was characterized as a mixture of two ferulates with an
      unusual skeleton by spectral and chemical methods, including by NMR, GC-MS and
      chemical derivatization. This fraction also showed moderate scavenging effect
      against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals.

PMID- 11314960
TI  - Inhibitors of platelet lipoxygenase from Ponkan fruit.
AB  - An activity-guided separation for inhibitors of rat platelet 12-lipoxygenase led
      to the isolation of two compounds, 4-O-feruloyl-5-O-caffeoylquinic acid (IC50;
      5.5 microM) and methyl 4-O-feruloyl-5-O-caffeoylquinate (IC50; 1.9 microM) from
      the peel of Ponkan fruit (Citrus reticulata). The complete structure of each
      phenolic ester was determined by NMR spectroscopy [1H and 13C NMR spectra, 1H-1H
      correlation spectroscopy (COSY), 1H-detected heteronuclear multiple quantum
      coherence (HMQC), and heteronuclear multiple bond connectivity (HMBC)
      spectroscopies] and other spectral methods.

PMID- 11314961
TI  - Soybean ethanol extract increases the function of osteoblastic MC3T3-E1 cells.
AB  - To investigate the bioactivities of soybean, which act on bone metabolism, we
      studied the effect of a soybean ethanol extract on the activity of osteoblast
      MC3T3-E1 cells. Soy extract (0.01-0.1 g/l) dose-dependently increased survival
      (P<0.05) and DNA synthesis (P<0.05) of MC3T3-E1 cells. In addition, soy extract
      (0.05 g/l) increased alkaline phosphatase activity (P<0.05) and collagen
      synthesis (P<0.05) of MC3T3-E1 cells. Moreover, the anti-estrogen tamoxifen
      eliminated the stimulation of MC3T3-E1 cells on the proliferation, ALP activity
      and collagen synthesis by soy extract, indicating that the main action of the soy
      extract on osteoblastic MC3T3-E1 cells is similar to that of estrogen effects.
      Treatment with soy extract prevented apoptosis, as assessed by a one-step
      sandwich immunoassay and DNA gel electrophoresis studies. This effect may be
      associated with the activation of the estrogen receptor, since we observed soy
      extract-mediated survival against apoptosis was blocked by the estrogen receptor
      antagonist tamoxifen in cells, further supporting a receptor-mediated mechanism
      of cell survival. These results suggest that osteoblast function is promoted by
      soy extract and that the estrogen receptor is involved in the response, thereby
      playing an important role in bone remodeling. In conclusion, soy extract has a
      direct stimulatory effect on bone formation in cultured osteoblastic cell in
      vitro. Presumably, dietary soy products are useful in the prevention of
      osteoporosis.

PMID- 11314962
TI  - Withanolide-type steroids from Solanum cilistum.
AB  - Six withanolide-type steroids, named as cilistols a, b, d, q, g and f,
      respectively, were isolated from the leaves of Solanum cilistum. The major
      component among them, cilistol a, was characterized as (22R, 24S, 25R, 26R)-1-oxo
      22, 26; 24, 25-diepoxy-17alpha, 26-dihydroxyergost-2,5-diene on the basis of
      spectroscopic properties and X-ray crystallographic analysis; the other isolated
      compounds had closely related structures. This is the first report of withanolide
      type steroids in the Solanum genera.

PMID- 11314963
TI  - Pyrone and pyridone compounds in the liquid culture of Physisporinus
      sanguinolentus.
AB  - Chromatographic separation of the liquid culture filtrate of the basidiomycete
      fungus Physisporinus sanguinolentus has yielded three new compounds viz., 2
      methyl-4-pyrone, 2-methyl-5,6-dihydro-4-pyrone and the pyridone form of 4-hydroxy
      2-methylpyridine, together with the known triacetic acid lactone, the
      sesquiterpene dialdehyde merulidial and a derivative of merulidial. Their
      structures were elucidated by spectroscopic analysis and by comparison to
      literature data and a synthetic sample. One of the compounds, merulidial, was
      shown to inhibit the germination of spores and the hyphal growth of the wood
      rotting basidiomycete Heterobasidion annosum and the saprophytic mould
      Cladosporium cucumerinum.

PMID- 11314964
TI  - Four alkaloids from Annona cherimola.
AB  - Four alkaloids, annocherine A, annocherine B, cherianoine, and romucosine H,
      along with one known alkaloid, artabonatine B, were isolated from the MeOH
      extract of the stems of Annona cherimola. Their structures were identified on the
      basis of both analysis of their spectral data and from chemical evidence.

PMID- 11314965
TI  - Phenolic constituents from the core of kenaf (Hibiscus cannabinus).
AB  - Four lignans, boehmenan H [2-(4-hydroxy-3-methoxyphenyl)-5-[3-(4-hydroxy-3
      methoxycinnamoyloxy)propyl]-3-hydroxymethyl-7-methoxybenzodihydrofuran],
      boehmenan K [2-(4-hydroxy-3-methoxyphenyl)-5-[3-(4-hydroxycinnamoyloxy)-1
      propenyl]-3-(4-hydroxy-3-methoxycinnamoyloxymethyl)-7-methoxybenzodihydrofuran],
      threo-carolignan H [threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-[3-(4-hydroxy-3
      methoxycinnamoyloxy)propyl]-2-methoxyphenoxy]-1,3-propanodiol], and threo
      carolignan K [threo-1-(4-hydroxy-3-methoxyphenyl)-3-(4-hydroxy-3
      methoxycinnamoyloxy)-2-[4-[3-(4-hydroxycinnamoyloxy)-1-propenyl]-2
      methoxyphenoxy]-1-propanol] as well as several other lignans, aldehydes and a
      tyramine derivative were isolated from the acetone extract of core of kenaf
      (Hibiscus cannabinus). All the structures were established by spectroscopic
      methods. The hitherto unreported 13C NMR spectra of some compounds are also
      presented and discussed. 2D NMR techniques have allowed the revision of certain
      previously reported 13C NMR assignments of some scarce naturally occurring
      compounds.

PMID- 11314966
TI  - Erysubins C-F, four isoflavonoids from Erythrina suberosa var. glabrescences.
AB  - Four isoflavonoids, erysubins C-F, together with ten known compounds were
      isolated from the roots of Erythrina suberosa var. glabrescences, and their
      structures were elucidated on the basis of spectroscopic evidence. Erysubin C is
      an unusual pterocarpan derivative with a formyl group.

PMID- 11314967
TI  - A pregnane steroid from Aglaia lawii and structure confirmation of cabraleadiol
      monoacetate by X-ray crystallography.
AB  - The pregnane steroid, (E)-aglawone, along with four known triterpenes, and a
      known sterol mixture were isolated from the bark of Aglaia lawii (Wight) Saldanha
      ex Ramamoorty (Meliaceae). The structural determination/identification was
      accomplished by a combination of 1D- and 2D-NMR spectroscopic techniques. The
      relative stereochemistry of the known triterpene, 20S,24S-epoxydammarane
      3alpha,25-diol acetate, was also unequivocally determined for the first time by X
      ray crystallography. The isolates were not active against various human cancer
      cell lines.

PMID- 11314968
TI  - Alkyl phenols and derivatives from Tapirira obtusa.
AB  - From the bark of Tapiria obtusa, six alkyl phenol derivatives were isolated: 1
      hydroxy-3-[(Z)-7'-nonadecenyl]-benzene, 1-hydroxy-3-[(Z)-7'-heptadecenyl]
      benzene, 1-hydroxy-3-[14'-phenyltetradecyl]-benzene, and 1-hydroxy-3-[16'
      phenyltetradecyl]-benzene, and their possible biogenetic precursors, 1-(16'
      phenyl-12'Z-hexadecenyl)-4-Z-cyclohexene-(1S*,3S*)-diol and (4S*,6S*)-dihydroxy-6
      (14'Z-nonadecenyl)-2-cyclohexenone. The structures of these compounds were
      elucidated by chemical and spectroscopic analysis, (4S*,6S*)-Dihydroxy-6-(14'Z
      nonadecenyl)-2-cyclohexenone showed cytotoxic activity.

PMID- 11314969
TI  - Changes in serum copper level during detoxification of acutely poisoned drug
      addicts.
AB  - Although it is known that drug addicts are a high-risk group for disruption of
      many homeostatic processes, little is know about changes in serum trace elements
      concentrations after taking the psychoactive substances. The aim of the study was
      to check the influence of the taking homemade heroin on serum level of copper.
      Blood samples were taken from 30 opiate addicts, and copper concentrations were
      measured by the means of atomic absorption spectrophotometry. The result of the
      study show that in the examined group, copper serum concentrations (1.35 mg/L)
      upon admission to the clinic were higher than in the control group (1.11 mg/L)
      but decreased during hospitalization (1.18 mg/L). There was no correlation
      between duration of stay at the hospital and changes in serum copper
      concentration.

PMID- 11314970
TI  - Comparison of chromosome damage induced by three zinc compounds using human
      leukocyte culture.
AB  - The degree of chromosome damage induced by three compounds of zinc (zinc
      chloride, zinc sulfate, zinc acetate) was compared in human leucocytes in vitro.
      Three concentrations of each salt, 3.0 x 10(-5)M, 3.0 x 10(-4)M, and 1.5 x 10(
      3)M, were added to leukocyte cultures. The cells were harvested after 48 and 72 h
      and chromosome spreads were prepared following a colchicine-hypotonic-fixation
      air drying-Giemsa staining schedule. The end point screened was chromosome
      aberrations. All three salts were lethal at the highest concentration. The degree
      of chromosome damage was directly proportional to the concentrations used for
      zinc sulfate and zinc acetate but not for zinc chloride.

PMID- 11314971
TI  - Relative and combined effects of ethanol and protein deficiency on some hair
      trace elements: lack of relationship with body stores.
AB  - This study was performed in order to analyze the relative and combined effects of
      ethanol and protein deficiency on hair copper, zinc, manganese, and iron content
      in four groups of seven animals each which were pair-fed during 8 wk with (1) a
      nutritionally adequate diet, (2) a 36% (as energy) ethanol-containing isocaloric
      diet, (3) a 2% protein, isocaloric diet, and (4) a 36% ethanol, 2% protein
      isocaloric diet, respectively, following the Lieber-DeCarli model, and to analyze
      the relationship between hair copper, zinc, manganese, and iron content, and the
      liver and muscle content of these elements. Although there was a trend to higher
      levels of all the elements analyzed in the the hair of the low-protein fed
      animals, differences were statistically significant regarding copper and
      manganese, effects being solely attributable to the low protein diet, not to
      ethanol. Moreover, hair copper was significantly, inversely related with final
      weight and weight loss. There were significant relationship between liver zinc
      and muscle zinc (r = 0.57, p = 0.002), but not between liver or muscle zinc and
      hair zinc; no correlations were observed between muscle copper and hair copper,
      nor between liver manganese and hair manganese. An inverse, statistically
      significant correlation was observed between liver copper and hair copper (r = 
      0.39, p < 0.05).

PMID- 11314972
TI  - Pleural effusions and sera from patients with benign or malignant diseases.
AB  - In pleural effusions and sera from 66 patients copper and zinc were quantified by
      inductively coupled argon plasma-mass spectrometry after mineralizations in a
      closed-pressurized microwave unit with a mixture of concentrated nitric acid and
      30% hydrogen peroxide. Total protein, pH, leukocyte count, lactate dehydrogenase,
      glucose, C-reactive protein, ceruloplasmin, and alpha1-antitrypsin were
      determined in many of the effusions. All but four effusions had concentrations of
      copper (range 58-1720 microg/kg) and zinc (range 27-1001 microg/kg) that were
      lower than the concentrations in the corresponding sera. Very high concentrations
      of zinc (1930-6470 microg/kg) were characteristic for thoracic empyemata. In the
      scatterplots of serum copper versus effusion copper, serum zinc versus effusion
      zinc, and serum copper/effusion copper versus serum zinc/effusion zinc no clearly
      delineated regions were noticeably useful for identifying malignant effusions.
      Similar plots of the concentrations of copper or zinc versus the eight clinical
      laboratory parameters or plots of clinical parameter versus clinical parameter
      failed to be of diagnostic value. Statistically highly significant correlations
      (p < or = 0.05, n > 45, r2 > 0.25) were observed for 9 of 28 pairs of the
      clinical parameters, for total protein and copper in the effusions and zinc in
      the effusions and for ceruloplasmin and copper in the effusions. Among the
      patients suffering from benign or malignant effusions, 52% had zinc
      concentrations in the sera below the low limit of the normal range (600
      microg/kg). Supplementation of such patients with zinc should be considered.

PMID- 11314973
TI  - Trace element distribution in heart tissue sections studied by nuclear microscopy
      is changed in Coxsackie virus B3 myocarditis in methyl mercury-exposed mice.
AB  - Methyl mercury (MeHg) has been shown to change Coxsackie virus type B3 (CB3)
      myocarditis in a direction compatible with the development of chronic disease.
      Murine models of CB3 myocarditis closely mimic the pathogenesis in humans. There
      are also indications that metals, such as mercury, and trace elements may
      interact and adversely affect viral replication and development of inflammatory
      lesions. The effects of low-dose MeHg exposure on myocardial trace element
      distribution, as determined by means of nuclear microscopy, was studied in CB3
      myocarditis. Balb/c mice were fed a MeHg-containing diet (3.9 mg/kg diet) for 12
      wk prior to infection. Areas of inflammatory lesions in the myocardium were
      identified by traditional histologic examination, and serial tissue sections in
      these selected areas were used for immune histology (macrophages), in situ
      hybridization of virus genomes, and nuclear microscopy of tissue trace element
      distribution. Areas with no inflammation or virus were compared with areas of
      ongoing inflammation and viral replication. In the inflammatory lesions of MeHg
      exposed mice as compared to nonexposed mice, the myocardial contents of calcium
      (Ca), manganese (Mn), and iron (Fe) were significantly increased, whereas the
      zinc (Zn) content was decreased. The increased Ca and decreased Zn contents in
      the inflamed heart may partly explain a more severe disease in MeHg-exposed
      individuals. Although not significant in the present study, with a limited number
      of mice, the inflammatory and necrotic lesions in the ventricular myocardium on d
      7 of the infection was increased by 50% (from 2.2% to 3.3% of the tissue section
      area) in MeHg-exposed mice and, also, there was a tendency of increased
      persistence of virus with MeHg exposure. No increased MeHg uptake, either in the
      inflammatory lesions or in the areas of noninflamed heart tissue in infected
      mice, could be detected. The present results indicate that a "competition" exists
      between potentially toxic heavy metals from the environment/diet and important
      trace elements in the body and that a disturbed trace element balance adversely
      influences the development of pathophysiologic changes in inflammatory heart
      disease.

PMID- 11314974
TI  - Effect of cold-restraint stress on the distribution of trace elements in rat
      tissues.
AB  - The aim of this study was to assess the effects of cold-restraint stress on blood
      and the other tissue levels of trace elements. The experiment was performed on
      male Swiss albino rats. The animals were divided to two groups: control and
      stressed groups. In the stressed group, the rats were subjected to immobilization
      for 4 h at 4 degrees C. At the end of the experimental period, blood and tissue
      samples were collected from all of the animals. The levels of zinc, copper,
      magnesium, and manganese were measured using flame and graphite furnace atomic
      absorption spectrometry. In rats subjected to stress, the zinc levels of serum
      were increased, whereas in the duodenum and brain, zinc was found to decrease
      when compared to the control. The magnesium content of both the stomach and
      duodenum were reduced, but the manganese levels of the liver, kidneys, and brain
      significantly increased because of stress. In conclusion, cold-restraint stress
      may affect the metabolic process by changing the distributions of zinc,
      magnesium, and manganese in tissues.

PMID- 11314975
TI  - Inhibitory effects of sophoraflavanones B and H in Sophora mooracroftiana Beth ex
      Baker on copper-ion-induced protein oxidative modification of mice brain
      homogenate in vitro.
AB  - We present the results of an in vitro investigation of the inhibitory effects of
      sophoraflavanones B and H isolated from Sophora mooracroftiana Beth ex Baker on
      copper-induced protein oxidative modification. They inhibited copper-induced
      protein oxidative modification. Their effects were stronger than those of
      naringenin as a related flavanone, and of mannitol as a hydroxyl radical
      scavenger. The results suggest that these natural products may be of use in cases
      where oxidative stress is present.

PMID- 11314976
TI  - Zinc toxicity in various lung cell lines is mediated by glutathione and GSSG
      reductase activity.
AB  - In a previous work, it was shown that in cells after a decrease of cellular
      glutathione content, toxic zinc effects, such as protein synthesis inhibition or
      GSSG (glutathione, oxidized form) increases, were enhanced. In this study, zinc
      toxicity was determined by detection of methionine incorporation as a parameter
      of protein synthesis and GSSG increase in various lung cell lines (A549, L2,
      11Lu, 16Lu), dependent on enhanced GSSG reductase activities and changed
      glutathione contents. After pretreatment of cells with DL-buthionine-[R,S]
      sulfoximine (BSO) for 72 h, cellular glutathione contents were decreased to 15
      40% and GSSG reductase activity was increased to 120-135% in a concentration
      dependent manner. In BSO pretreated cells, the IC50 values of zinc for methionine
      incorporation inhibition were unchanged as compared to cells not pretreated. The
      GSSG increase in BSO pretreated cells by zinc was enhanced in L2, 11Lu, and 16Lu
      cells, whereas in A549 cells, the GSSG increase by zinc was enhanced only after
      pretreatment with the highest BSO concentration. Inhibition of GSSG reductase in
      alveolar epithelial cells was observed at lower zinc concentrations than needed
      for methionine incorporation inhibition, whereas in fibroblastlike cells,
      inhibition of GSSG reductase occurred at markedly higher zinc concentrations as
      compared to methionine incorporation inhibition. These results demonstrate that
      GSSG reductase is an important factor in cellular zinc susceptibility. We
      conclude that reduction of GSSG is reduced in zinc-exposed cells. Therefore,
      protection of GSH oxidation by various antioxidants as well as enhancement of GSH
      content are expected to be mechanisms of diminishing toxic cellular effects after
      exposure to zinc.

PMID- 11314977
TI  - Marginal copper deficiency and atherosclerosis.
AB  - Copper is an essential trace element in the maintenance of the cardiovascular
      system. Copper-deficient diets can elicit, in animals, structural and functional
      changes that are comparable to those observed in coronary heart disease. In this
      study, the effect of dietary-induced copper deficiency on aortic lesion
      development was measured by quantitative image analysis in C57BL/6 mice that are
      susceptible to diet-induced aortic lesions. The diets administered were severely
      copper deficient (0.2 mg/kg diet), marginally deficient (0.6 mg/kg diet), or
      copper adequate (6.0 mg/kg diet). Similarly, increased aortic lesion areas and
      elevated serum cholesterol were demonstrated in both deficient groups, compared
      with the copper-adequate group. Evidence for graded differences in copper status
      among the dietary groups was shown by the dose-response increase in liver copper
      concentration, copper-zinc superoxide dismutase and cytochrome-c oxidase
      activities, together with serum caeruloplasmin oxidase with increasing intakes of
      dietary copper. Despite the difference in copper status between the copper
      marginal and severely deficient groups, similar lesions found in both groups of
      mice suggest a threshold effect of copper deficiency on lesion formation.

PMID- 11314978
TI  - Influence of excessive fluoride consumption on the severity of dystrophic cardiac
      calcification in DBA/2 mice.
AB  - Soft tissue calcifications in inbred laboratory mice are frequently observed and
      are often associated with dystrophic cardiac calcinosis (DCC). We tested the
      hypothesis that an excessive intake of fluoride would inhibit pathological
      calcifications in DCC-susceptible mice. A diet containing either a high (200 mg
      F/kg added to the diet) or low fluoride content (no F added) was fed to both
      weanling and retired breeder DBA/2 mice. The high-fluoride diet reduced feed
      intake and body weight gain when given after weaning. It was found that a high
      fluoride intake effectively reduces soft tissue calcifications in young mice, but
      not in retired breeders. Because DCC in mice is a pathological finding that could
      interfere with certain experimental procedures, it is suggested that the optimum
      fluoride concentration in the diet for mice of susceptible strains should be
      established.

PMID- 11314979
TI  - Biological roles of titanium.
AB  - Ti4+ in soil is a natural antibiotic mobilized by bacteria-generated H+. When
      added to the diet of young mice, Ti4+ enhanced their growth. These and
      observations of others indicate that Ti4+ has a variety of biological roles.

PMID- 11314980
TI  - Cadmium-induced liver, heart, and spleen lipid peroxidation in rats and
      protection by selenium.
AB  - The purpose of this study was to evaluate the effects of cadmium-induced
      peroxidative damage to rat liver, heart, and spleen. Sprague-Dawley rats were
      injected subcutaneously with a single dose of 25, 125, 500, or 1250 microg Cd/kg
      and evaluated 6, 12, 24, or 72 h later. Liver, heart, and spleen were analyzed
      for lipid peroxidation and Fe, Cu, Zn, Se, and Cd concentrations. Data showed
      that Cd produced enhanced lipid peroxidation in the liver, heart, and spleen.
      These Cd-induced changes were accompanied by a significant rise in liver, heart,
      and spleen Fe and Cu, and a fall in spleen Zn and liver, heart, and spleen Se.
      Concurrent treatment with Se and Cd reduced the Cd-induced alterations in liver,
      heart, and spleen peroxidation and essential metal levels. Data suggest that
      lipid peroxidation is associated with cadmium toxicity and that Se was found
      effective in preventing lipid peroxidation.

PMID- 11314981
TI  - Increased zinc absorption but not secretion in the small intestine of
      metallothionein-null mice.
AB  - Metallothionein (MT) has been assigned a role in intestinal Zn absorption and
      secretion. The influence of MT was investigated in isolated segments of the small
      intestine from mice lacking the expression of MT I and II genes (MT-/-). To
      measure Zn absorption, washed 10- to 12-cm segments of the proximal and distal
      small intestine of MT-/- and control MT+/+ mice were filled with 65Zn as ZnSO4
      (10 microg/mL), and the amount of 65Zn appearing in the external buffer was
      measured over 4 h. To measure Zn secretion, the same procedure was followed using
      everted gut segments. The 65Zn absorption from the small intestine was
      significantly greater in MT-/- mice, but only in the absence of albumin. In the
      proximal small intestine, the inclusion of 2% albumin in the external buffer
      significantly increased Zn absorption from 6.8% (no albumin) to 13.2% (with
      albumin) for MT-/-, and from 4.9% (no albumin) to 14.2% (with albumin) for MT+/+.
      In the distal segment, the respective values, with and without albumin
      respectively were 9.5% and 15.1% for MT-/- mice and 4.3% and 16.1% for MT+/+
      mice. Regarding 65Zn secretion, there was no difference between MT+/+ and MT-/-
      in either segment. However, the rate of secretion was higher in the proximal
      small intestine for both genotypes. Although it can be demonstrated that MT
      limits Zn absorption under controlled conditions in vitro, the ability of albumin
      to overcome this effect emphasizes the importance of circulating ligands in Zn
      transport.

PMID- 11314983
TI  - Effect of surgically induced cholestasis on the levels of hepatic zinc and
      metallothionein in rat liver.
AB  - Early effects of experimental cholestasis on the homeostasis of zinc (Zn) and
      metallothionein (MT) were studied in rats which had undergone bile duct ligation
      for 0, 3, 6, 9, 12, 16, 20, and 24 h. Transient increases in hepatic Zn levels
      were observed at 9 h but returned to control values at 12 h. Serum Zn levels
      increased at 24 h. Cholestasis was confirmed by increased serum alkaline
      phosphatase (AP) activity. MT increased at 3 h and reached a maximum level at 12
      h and remained elevated even at 24 h after the onset of experimental cholestasis.
      No hepatocellular damage was detected according to the results of alanine
      aminotransferase (ALT) activities in serum. These results shown that the
      increases in Zn observed in liver are related to bile stagnation rather than to a
      hepatocellular damage and that increased MT occurs concurrently with increased
      hepatic Zn. These observations suggest that the cellular levels of Zn in
      cholestasis is regulated by homeostatic mechanisms, of which one could be
      mediated by MT.

PMID- 11314982
TI  - Effect of arsenic trioxide on metallothionein and its conversion to different
      arsenic metabolites in hen liver.
AB  - The metabolism of arsenic, its affinity to metallothionein (MT), its influence on
      selenium levels, and its biotransformation to different metabolites in the liver
      tissue of laying hens exposed to arsenic trioxide (As2O3) was investigated. The
      experiment was performed with two groups of hens fed for 19 d with either a
      standard diet or with the same diet enriched in arsenic (30 microg/g). The major
      findings were as follows: 1. After 19 d exposure, about 65% of the total liver As
      was found in the water-soluble phase (100,000g centrifuged supernatant). In liver
      supernatant, As binding was found mostly in the range of very low-molecular
      weight proteins (Mr < 10,000). Although after exposure the amount of MT-like
      proteins increased, the As bound to it was only in trace amounts. The protein was
      identified by convential procedures as Zn,Cu-thionein with traces of selenium and
      arsenic. 2. Arsenic exposure resulted in almost unchanged Se levels regarding its
      tissue concentrations and distribution between supernatant and pellet, where
      about 10% of total Se was found in the supernatant. On the contrary, As exposure
      did affect Cd levels. Tissue Cd concentration was slightly diminished, but the
      percentage of tissue Cd found in the water-soluble phase was increased from 20%
      to 40%. 3. In methanol extracts of tissue and supernatant of the As-exposed
      group, only two arsenic compounds were detected, As(III) and dimethylarsinic acid
      (DMA), the latter prevailing.

PMID- 11314984
TI  - Effect of lanthanum on ion absorption in cucumber seedling leaves.
AB  - Scanning electron microscope and energy-dispersive X-ray analysis were used to
      study the tissular distributions of elements Na, Mg, Cl, K, Ca, Mn, and Fe in
      leaves of cucumber seedlings in the absence or presence of La3+. The results
      showed that the atomic percentages of Na, Mg, Cl, K, and Ca were basically
      reduced and those of Mn and Fe were increased in the presence of La3+; in
      addition, at 0.02 mM La3+, the reduced or increased degrees were higher than
      those at 2.0 mM La3+. The effects of La3+ on ion absorption were similar to those
      of Ca2+, suggesting that the rare earth element lanthanum affects the plant
      physiological mechanism by regulating the Ca2+ level in plant cell.

PMID- 11314985
TI  - Determination of total aluminum, chromium, copper, iron, manganese, and nickel
      and their fractions leached to the infusions of black tea, green tea, Hibiscus
      sabdariffa, and Ilex paraguariensis (mate) by ETA-AAS.
AB  - Total aluminum, chromium, copper, iron, manganese, and nickel were determined in
      black tea, green tea, Hibiscus sabdariffa, and Ilex paraguariensis (mate) by
      electrothermal atomic absorption spectrometry after nitric/perchloric acid
      digestion. In each case, one ground sample of commercially available leafy
      material was prepared and three 0.5-g subsamples were run in parallel. The
      infusions were also analyzed and the percentage of each element leached into the
      liquor was evaluated. The obtained results indicated that hibiscus and mate
      contained lower levels of aluminum (272+/-19 microg/g and 369+/-22 microg/g,
      respectively) as referred to black tea (759+/-31 microg/g) or green tea
      (919micro29 microg/g) and suggested that mate drinking could be a good dietary
      source of essential micronutrient manganese (total content 2223+/-110 microg/g,
      48.1% leached to the infusion). It was also found that the infusion of hibiscus
      could supply greater amounts of iron (111+/-5 microg/g total, 40.5% leached) and
      copper (5.9+/-0.3 microg/g total, 93.4% leached) as compared to other infusions.
      Moreover, it was found that the percentage of element leached to the infusion was
      strongly related to the tannins content in the beverage (correlation coefficients
      > 0.82 with the exception for nickel); for lower tannins level, better leaching
      was observed.

PMID- 11314986
TI  - Thyroid hypofunction in Down's syndrome: is it related to oxidative stress?
AB  - Oxidative stress affecting the thyroxin biosynthesis might explain the proneness
      of patients with Down's syndrome (DS) (trisomia 21) to develop hypothyroidism.
      Thyroideal cells are exposed to endogenous H2O2 that acts as a cofactor for the
      iodination of thyroxin precursors. The gland has high levels of selenium
      containing proteins, including peroxide-detoxicating enzyme proteins. The object
      of the present study was to explore the hypothesis of a role of an imbalance
      between toxic oxygen production and protective metalloenzymes during the
      development of thyroid hypofunction in DS patients. We analyzed serum levels of
      thyroid hormones and trace metals in 38 institutionalized adults with DS, using
      mentally retarded subjects matched for age, sex, and behavioral function as
      controls. The DS patients had significantly lower mean values of free thyroxin
      (fT4) and increased TSH (thyroid stimulating hormone), as compared to the
      controls. They had lower serum selenium than the controls. A positive correlation
      was observed between serum concentrations of fT4 and selenium in the DS patients
      (r = 0.393, p < 0.05). No significant differences were found between the fT4 or
      the TSH concentrations in the patients with and without circulating antithyroid
      autoantibodies. Our results support the suggestion that thyroid hypofunction in
      patients with Down's syndrome in some way is linked to the low serum levels of
      selenium found in these patients. It is suggested that selenium-containing
      proteins are involved in thyroid hormonal synthesis, by protecting biosynthetic
      processes against the toxicity of free oxygen radicals.

PMID- 11314987
TI  - Differences in the mineral contents between falx cerebri and tentorium cerebelli.
AB  - To elucidate age-related changes of the dura mater, the authors investigated age
      related changes of mineral contents in the falx cerebri and the tentorium
      cerebelli by inductively coupled plasma-atomic emission spectrometry. The
      subjects consisted of 10 men and 15 women, ranging in age from 65 to 102 yr. The
      contents of calcium, phosphorus, and magnesium increased progressively with aging
      in the falx cerebri, whereas the contents of sulfur, iron, and zinc remained
      constant, being independent of age. In regard to the tentorium cerebelli, the
      contents of calcium, phosphorus, and magnesium seemed to increase progressively
      with aging, but the contents of sulfur, iron, and zinc hardly changed with aging.
      It was noteworthy that there were no significant relationships between the falx
      cerebri and the tentorium cerebelli in such element contents as calcium,
      phosphorus, magnesium, sulfur, iron, and zinc.

PMID- 11314988
TI  - Concentrations of copper, zinc, manganese, rubidium, and magnesium in thoracic
      empyemata and corresponding sera.
AB  - In this study, a number of selected trace elements and clinically relevant
      parameters were compared between thoracic empyemata and the corresponding sera
      for a better understanding of the trace element distribution between these two
      compartments. Serumempyema pairs were obtained from 13 patients and quantified
      for selected and essential trace elements, namely copper (Cu), zinc (Zn),
      manganese (Mn), rubidium (Rb), and magnesium (Mg), by inductively coupled plasma
      mass spectrometry (ICP-MS). In addition, the concentrations of the following
      clinical laboratory parameters were analyzed by standard methods: total protein,
      leukocyte count, lactate dehydrogenase, glucose, pH, and the C-reactive protein.
      Individual concentrations of the elements determined in the empyemata were
      frequently higher than in pleural effusions of any other benign or malignant
      condition except for Cu. Serum Cu exceeded the normal range (600-1400 microg/kg)
      in 6 out of 13 patients (median 1410 microg/kg). In the empyemata, Zn
      concentrations (median 2000 microg/kg) were characteristically higher than in the
      sera (median 450 microg/kg) and exceeded the upper limit for serum (1200
      microg/kg) in 8 of the 13 patients. Manganese concentrations in the empyemata
      (median 2.7 microg/kg) were also higher compared to corresponding sera, although
      they stayed within the limits considered normal for serum of healthy adults
      (upper limit 2.9 microg/kg). Rubidium was also moderately higher in most
      empyemata (median 290 microg/kg) and exceeded the upper limit for serum (560
      microg/kg) in two patients. The median concentration of the essential element
      magnesium was higher in the empyemata (23 mg/kg) than in the sera (21 mg/kg).
      However, all serum Mg concentrations except three remained within the normal
      range (17-22 mg/kg). Removal of large amounts of empyematous fluid may deprive
      the body of trace elements and can cause suboptimal or deficient trace element
      status and homeostasis. Recuperation will be accelerated by compensatory
      supplementation of trace elements. Therefore, selective medication with adequate
      trace element compounds in patients with thoracic empyema can be generally
      recommended for zinc. The other elements need not necessarily be monitored or
      substituted, because of their stable concentrations in the serum. Rb may have a
      biological impact, but deficiency symptoms in man are not clearly defined.

PMID- 11314989
TI  - Method developments for iodine speciation by reversed-phase liquid chromatography
      ICP-mass spectrometry.
AB  - Method developments are described for a iodine speciation method. This method is
      based on a reversed-phase liquid chromatography separation combined with
      inductively coupled plasma-mass spectrometry detection. Investigations are
      performed concerning the methanol tolerance/stability of inductively coupled
      plasma, postcolumn oxidation/volatilization of iodine from species, influences of
      buffer pH, and column temperature on separation efficiency. The experiments
      focused on six iodine species, namely iodine, monoiodothyrosine, di
      iodothyrosine, tri-iodothyronine, reversed tri-iodothyronine, and thyroxin.
      Detection limits were determined between 0.08 and 1.5 microg/L (iodine related),
      dependent on species. Appplications on a urine sample were performed, showing
      iodide as the predominant iodine species.

PMID- 11314990
TI  - Iodine speciation in human serum by reversed-phase liquid chromatography-ICP-mass
      spectrometry.
AB  - Reversed-phase liquid chromatography-inductively coupled plasma mass
      spectrometric hyphenation was used for iodine speciation in human serum. First
      investigations showed that iodine species nearly quantitatively were eluted in
      the void volume. The result indicated that protein-linked thyroid hormones were
      not interacting with the stationary phase, thus being not retained.
      Investigations were performed about T4-TBG (thyroxin-thyroxin-binding globulin)
      complex generation and its retention during chromatography. It was shown that T4
      TBG was not retained on the column. Therefore, a protease treatment was
      introduced for serum sample preparation. The analysis of "normal" sera (after
      protease) gave reasonable results lying in the range published in literature: I
      :11; di-iodothyrosine (DIT): 2.1; mono-iodothyrosine (MIT): 1.6; reversed tri
      iodothyronine (rT3): 3.9; T3: 5.9; T4: 60; each micrograms iodine per liter. The
      method also proved to recognize abnormalities in a pathologic serum, having rT3
      as the predominant species. In this case the method obviously was superior
      compared to standard immunoassay methods, as it is monitoring the iodine in the
      species (physiologically active iodine species), whereas immunoassay methods may
      sometimes detect deiodinated (inactive) compounds.

PMID- 11314991
TI  - Potassium supplements' effect on potassium balance in athletes during prolonged
      hypokinetic and ambulatory conditions.
AB  - Electrolyte supplements may be used to prevent changes in electrolyte balance
      during hypokinesia (diminished movement). The aim of this study was to measure
      the effect of potassium (K) supplements on K balance during prolonged hypokinesia
      (HK). Studies were done during 30 d of a pre-HK period and during 364 d of an HK
      period. Forty male athletes aged 25.1+/-4.4 yr were chosen as subjects. They were
      divided equally into four groups: unsupplemented ambulatory control subjects
      (UACS), unsupplemented hypokinetic subjects (UHKS), supplemented hypokinetic
      subjects (SHKS) and supplemented ambulatory control subjects (SACS). The SHKS and
      UHKS groups were kept under an average walking distance of 0.7 km/d. The SACS and
      SHKS groups were supplemented daily with 50.0 mg elemental potassium chloride
      (KCl) per kilogram body weight. The K balance, fecal K excretion, urinary K,
      sodium (Na), and chloride (Cl) excretion, plasma K, Na, and Cl concentration,
      plasma renin activity (PRA) and plasma aldosterone (PA) concentration,
      anthropometric characteristics and peak oxygen uptake were measured. Negative K
      balance, fecal K excretion, urinary K, Na, and Cl excretion, plasma K, Na, and Cl
      concentration, and PRA and PA concentration increased significantly (p < or =
      0.01), whereas body weight and peak oxygen uptake decreased significantly in the
      SHKS and UHKS groups when compared with SACS and UACS groups. However, the
      measured parameters changed much faster and much more in SHKS group than UHKS
      group. By contrast, K balance, fecal, urinary, and plasma K, plasma hormones,
      body weight, and peak oxygen uptake did not change significantly in the SACS and
      UACS groups when compared with the baseline control values. It was concluded that
      prolonged HK induces a significant negative K balance associated with increased
      plasma K concentration and urinary and fecal K excretion. However, negative K
      balance appeared much faster and was much greater in the SHKS group than UHKS
      group. Thus, K supplementation was not effective in preventing negative K balance
      during prolonged HK.

PMID- 11314992
TI  - Likelihood ratios for evaluating DNA evidence when the suspect is found through a
      database search.
AB  - A crime has been committed, and a DNA profile of the perpetrator is obtained from
      the crime scene. A suspect with a matching profile is found. The problem of
      evaluating this DNA evidence in a forensic context, when the suspect is found
      through a database search, is analysed through a likelihood approach. The
      recommendations of the National Research Council of the U.S. are derived in this
      setting as the proper way of evaluating the evidence when finiteness of the
      population of possible perpetrators is not taken into account. When a finite
      population of possible perpetrators may be assumed, it is possible to take
      account of the sampling process that resulted in the actual database, so one can
      deal with the problem where a large proportion of the possible perpetrators
      belongs to the database in question. It is shown that the last approach does not
      in general result in a greater weight being assigned to the evidence, though it
      does when a sufficiently large amount of the possible perpetrators are in the
      database. The value of the likelihood ratio corresponding to the probable cause
      setting constitutes an upper bound for this weight, and the upper bound is only
      attained when all but one of the possible perpetrators are in the database.

PMID- 11314993
TI  - Simulated likelihood methods for complex double-platform line transect surveys.
AB  - The conventional line transect approach of estimating effective search width from
      the perpendicular distance distribution is inappropriate in certain types of
      surveys, e.g., when an unknown fraction of the animals on the track line is
      detected, the animals can be observed only at discrete points in time, there are
      errors in positional measurements, and covariate heterogeneity exists in
      detectability. For such situations a hazard probability framework for independent
      observer surveys is developed. The likelihood of the data, including observed
      positions of both initial and subsequent observations of animals, is established
      under the assumption of no measurement errors. To account for measurement errors
      and possibly other complexities, this likelihood is modified by a function
      estimated from extensive simulations. This general method of simulated likelihood
      is explained and the methodology applied to data from a double-platform survey of
      minke whales in the northeastern Atlantic in 1995.

PMID- 11314994
TI  - Marginally specified logistic-normal models for longitudinal binary data.
AB  - Likelihood-based inference for longitudinal binary data can be obtained using a
      generalized linear mixed model (Breslow, N. and Clayton, D. G., 1993, Journal of
      the American Statistical Association 88, 9-25; Wolfinger, R. and O'Connell, M.,
      1993, Journal of Statistical Computation and Simulation 48, 233-243), given the
      recent improvements in computational approaches. Alternatively, Fitzmaurice and
      Laird (1993, Biometrika 80, 141-151), Molenberghs and Lesaffre (1994, Journal of
      the American Statistical Association 89, 633-644), and Heagerty and Zeger (1996,
      Journal of the American Statistical Association 91, 1024-1036) have developed a
      likelihood-based inference that adopts a marginal mean regression parameter and
      completes full specification of the joint multivariate distribution through
      either canonical and/or marginal higher moment assumptions. Each of these
      marginal approaches is computationally intense and currently limited to small
      cluster sizes. In this manuscript, an alternative parameterization of the
      logistic-normal random effects model is adopted, and both likelihood and
      estimating equation approaches to parameter estimation are studied. A key feature
      of the proposed approach is that marginal regression parameters are adopted that
      still permit individual-level predictions or contrasts. An example is presented
      where scientific interest is in both the mean response and the covariance among
      repeated measurements.

PMID- 11314995
TI  - Approximate standard errors in semiparametric models.
AB  - We consider semiparametric models with p regressor terms and q smooth terms. We
      obtain an explicit expression for the estimate of the regression coefficients
      given by the back-fitting algorithm. The calculation of the standard errors of
      these estimates based on this expression is a considerable computational
      exercise. We present an alternative, approximate method of calculation that is
      less demanding. With smoothing splines, the method is exact, while with loess, it
      gives good estimates of standard errors. We assess the adequacy of our
      approximation and of another approximation with the help of two examples.

PMID- 11314996
TI  - Kriging with nonparametric variance function estimation.
AB  - A method for fitting regression models to data that exhibit spatial correlation
      and heteroskedasticity is proposed. It is well known that ignoring a nonconstant
      variance does not bias least-squares estimates of regression parameters; thus,
      data analysts are easily lead to the false belief that moderate
      heteroskedasticity can generally be ignored. Unfortunately, ignoring nonconstant
      variance when fitting variograms can seriously bias estimated correlation
      functions. By modeling heteroskedasticity and standardizing by estimated standard
      deviations, our approach eliminates this bias in the correlations. A combination
      of parametric and nonparametric regression techniques is used to iteratively
      estimate the various components of the model. The approach is demonstrated on a
      large data set of predicted nitrogen runoff from agricultural lands in the
      Midwest and Northern Plains regions of the U.S.A. For this data set, the model
      comprises three main components: (1) the mean function, which includes farming
      practice variables, local soil and climate characteristics, and the nitrogen
      application treatment, is assumed to be linear in the parameters and is fitted by
      generalized least squares; (2) the variance function, which contains a local and
      a spatial component whose shapes are left unspecified, is estimated by local
      linear regression; and (3) the spatial correlation function is estimated by
      fitting a parametric variogram model to the standardized residuals, with the
      standardization adjusting the variogram for the presence of heteroskedasticity.
      The fitting of these three components is iterated until convergence. The model
      provides an improved fit to the data compared with a previous model that ignored
      the heteroskedasticity and the spatial correlation.

PMID- 11314997
TI  - Estimation of the correlation between nutrient intake measures under restricted
      sampling.
AB  - Food frequency questionnaires (FFQs) are commonly used to assess dietary intake
      in epidemiologic research. To evaluate the FFQ reliability, the commonly used
      approach is to estimate the correlation coefficient between the data given in FFQ
      and those in food records (for example, 4-day food records [4DFR]) for nutrients
      of interest. However, in a dietary intervention study, a criterion for
      eligibility may be to select participants who have baseline FFQ-measured dietary
      intake of percent energy from fat above a prespecified quantity. Other
      instruments, such as the 4DFR, may be subsequently administrated only to eligible
      participants. Under these circumstances, analysis without adjusting for the
      restricted population will usually lead to biased estimation of correlation
      coefficients and other parameters of interest. In this paper, we apply likelihood
      based and multiple imputation (MI) methods to accommodate such incomplete data
      obtained as a result of the study design. A simulation study is conducted to
      examine finite sample performance of various estimators. We note that both the MI
      estimate and the maximum likelihood (ML) estimate based on a bivariate-normal
      model are not sensitive to departures from this normality assumption. This led us
      to investigate robustness properties of the ML estimator analytically. We present
      some data analyses from a dietary assessment study from the Women's Health
      Initiative to illustrate the methods.

PMID- 11314998
TI  - Using pooled exposure assessment to improve efficiency in case-control studies.
AB  - Assays can be so expensive that interesting hypotheses become impractical to
      study epidemiologically. One need not, however, perform an assay for everyone
      providing a biological specimen. We propose pooling equal-volume aliquots from
      randomly grouped sets of cases and randomly grouped sets of controls, and then
      assaying the smaller number of pooled samples. If an effect modifier is of
      concern, the pooling can be done within strata defined by that variable. For
      covariates assessed on individuals (e.g., questionnaire data), set-based
      counterparts are calculated by adding the values for the individuals in each set.
      The pooling set then becomes the unit of statistical analysis. We show that, with
      appropriate specification of a set-based logistic model, standard software yields
      a valid estimated exposure odds ratio, provided the multiplicative formulation is
      correct. Pooling minimizes the depletion of irreplaceable biological specimens
      and can enable additional exposures to be studied economically. Statistical power
      suffers very little compared with the usual, individual-based analysis. In
      settings where high assay costs constrain the number of people an investigator
      can afford to study, specimen pooling can make it possible to study more people
      and hence improve the study's statistical power with no increase in cost.

PMID- 11314999
TI  - Bayesian inference for small-sample capture-recapture data.
AB  - We consider data on the survival of a population of Cephalorhynchus hectori,
      Hector's dolphins, in a marine area of New Zealand. To estimate survival
      probabilities of animal populations, a multiple capture-recapture sampling scheme
      can be used. In this paper, we propose a practical methodology to derive
      approximations to posterior distributions based on Laplace methods. We show how
      to calculate Bayes estimates and credible intervals in this setting.

PMID- 11315000
TI  - Valid inference in random effects meta-analysis.
AB  - The standard approach to inference for random effects meta-analysis relies on
      approximating the null distribution of a test statistic by a standard normal
      distribution. This approximation is asymptotic on k, the number of studies, and
      can be substantially in error in medical meta-analyses, which often have only a
      few studies. This paper proposes permutation and ad hoc methods for testing with
      the random effects model. Under the group permutation method, we randomly switch
      the treatment and control group labels in each trial. This idea is similar to
      using a permutation distribution for a community intervention trial where
      communities are randomized in pairs. The permutation method theoretically
      controls the type I error rate for typical meta-analyses scenarios. We also
      suggest two ad hoc procedures. Our first suggestion is to use a t-reference
      distribution with k-1 degrees of freedom rather than a standard normal
      distribution for the usual random effects test statistic. We also investigate the
      use of a simple t-statistic on the reported treatment effects.

PMID- 11315001
TI  - Modeling a Poisson forest in variable elevations: a nonparametric Bayesian
      approach.
AB  - A nonparametric Bayesian formulation is given to the problem of modeling
      nonhomogeneous spatial point patterns influenced by concomitant variables. Only
      incomplete information on the concomitant variables is assumed, consisting of a
      relatively small number of point measurements. Residual variation, caused by
      other unmeasured influential factors, is modeled in terms of a spatially varying
      baseline intensity function. A Markov chain Monte Carlo scheme is proposed for
      the simultaneous nonparametric estimation of each unknown function in the model.
      The suggested method is illustrated by reanalysing a data set in Rathbun (1996,
      Biometrics 52, 226-242), and the estimated models are compared with those
      obtained by Rathbun.

PMID- 11315002
TI  - Treatment comparisons based on two-dimensional safety and efficacy alternatives
      in oncology trials.
AB  - In addition to their desired anticancer effects, most cancer treatments may also
      cause transient toxicity, permanent organ damage, or death. A critical question
      in comparing an experimental treatment to a standard is how much increase in an
      adverse event rate is an acceptable trade-off for achieving a targeted
      improvement in efficacy, or vice versa. We consider settings where one may
      characterize patient outcome as a bivariate (efficacy, safety) variable and
      quantify treatment effect as a corresponding two-dimensional parameter. A set of
      target parameters, each representing a clinically meaningful improvement over the
      standard, are elicited from the physician. Each target is a two-dimensional
      generalization of the usual one-dimensional shift parameter. We define the
      alternative hypothesis in the two-dimensional effect space as the convex hull of
      the sets of parameters that are at least as desirable as each target point. The
      rejection region is obtained by shifting the alternative toward (0,0) to achieve
      a given type I error, with sample size computed to achieve a given power at the
      targets. The method is illustrated by application to two cancer chemotherapy
      trials.

PMID- 11315003
TI  - Estimation in independent observer line transect surveys for clustered
      populations.
AB  - This paper introduces a framework for animal abundance estimation in independent
      observer line transect surveys of clustered populations. The framework
      generalizes an approach given in Chen (1999, Environmental and Ecological
      Statistics 6, in press) to accommodate heterogeneity in detection caused by
      cluster size and other covariates. Both parametric and nonparametric estimators
      for the local effective search widths, given the covariates, can be derived from
      the framework. A nonparametric estimator based on conditional kernel density
      estimation is proposed and studied owing to its flexibility in modeling the
      detection functions. A real data set on harbor porpoise in the North Sea is
      analyzed.

PMID- 11315004
TI  - Likelihood models for clustered binary and continuous outcomes: application to
      developmental toxicology.
AB  - In developmental toxicology, methods based on dose response modeling and
      quantitative risk assessment are being actively pursued. Among live fetuses, the
      presence of malformations and reduction in fetal weight are of primary interest,
      but ordinarily, the dose-response relationships are characterized in each of the
      outcomes separately while appropriately accounting for clustering within litters.
      Jointly modeling the outcomes, allowing different relationships with dose while
      incorporating the correlation between the fetuses and the outcomes, may be more
      appropriate. We propose a likelihood-based model that is an extension of a
      correlated probit model to incorporate continuous outcomes. Our model maintains a
      marginal dose-response interpretation for the individual outcomes while taking
      into account both the correlations between outcomes on an individual fetus and
      those due to clustering. The joint risk of malformation and low birth weight can
      then be estimated directly. This approach is particularly well suited to
      estimating safe dose levels as part of quantitative risk assessment.

PMID- 11315005
TI  - Local bandwidth selection for kernel estimation of population densities with line
      transect sampling.
AB  - Seber (1986, Biometrics 42, 267-292) suggested an approach to biological
      population density estimation using kernel estimates of the probability density
      of detection distances in line transect sampling. Chen (1996a, Applied Statistics
      45, 135-150) and others have employed cross validation to choose a global
      bandwidth for the kernel estimator or have suggested adaptive kernel estimation
      (Chen, 1996b, Biometrics 52, 1283-1294). Because estimation of the density is
      required at only a single point, we investigate a local bandwidth selection
      procedure that is a modification of the method of Schucany (1995, Journal of the
      American Statistical Association 90, 535-540) for nonparametric regression. We
      report on simulation results comparing the proposed method and a local normal
      scale rule with cross validation and adaptive estimation. The local bandwidths
      and normal scale rule produce estimates with mean squares that are half the size
      of the others in most cases. Consistency results are also provided.

PMID- 11315006
TI  - Using a mixed effects model to estimate geographic variation in cancer rates.
AB  - Commonly used methods for depicting geographic variation in cancer rates are
      based on rankings. They identify where the rates are high and low but do not
      indicate the magnitude of the rates nor their variability. Yet such measures of
      variability may be useful in suggesting which types of cancer warrant further
      analytic studies of localized risk factors. We consider a mixed effects model in
      which the logarithm of the mean Poisson rate is additive in fixed stratum effects
      (e.g., age effects) and in logarithms of random relative risk effects associated
      with geographic areas. These random effects are assumed to follow a gamma
      distribution with unit mean and variance 1/alpha, similar to Clayton and Kaldor
      (1987, Biometrics 43, 671-681). We present maximum likelihood and method-of
      moments estimates with standard errors for inference on alpha -1/2, the relative
      risk standard deviation (RRSD). The moment estimates rely on only the first two
      moments of the Poisson and gamma distributions but have larger standard errors
      than the maximum likelihood estimates. We compare these estimates with other
      measures of variability. Several examples suggest that the RRSD estimates have
      advantages compared to other measures of variability.

PMID- 11315007
TI  - A simple permutation-type method for testing circular uniformity with correlated
      angular measurements.
AB  - A simple method is provided for testing uniformity on the circle that allows
      dependence among repeated angular measurements on the same subject. Our null
      hypothesis is that the distribution of repeated angles is unaffected by rotation.
      This null can be evaluated with any test of uniformity by using a null reference
      distribution obtained by simulation, where each subject's vector of angles is
      rotated by a random amount. A new weighted version of the univariate Rayleigh
      test of circular uniformity is proposed.

PMID- 11315008
TI  - Efficiency of estimating vaccine efficacy for susceptibility and infectiousness:
      randomization by individual versus household.
AB  - In designing vaccine efficacy studies based on the secondary attack rate (SAR) or
      transmission probability in which both vaccine efficacy for susceptibility,
      VE(S), and vaccine efficacy for infectiousness, VE(I), are estimated, the
      allocation of vaccine and placebo within transmission units has an important
      influence on the efficiency of the study. We compared the following randomization
      schemes that result in different allocations of vaccine and placebo within two
      member households: (1) randomization by individual for a mixed allocation, (2)
      randomization by transmission unit for concordant allocation, and (3)
      randomization of only one individual in each transmission unit to either vaccine
      or placebo. There is a complex interaction among the VE(S), VE(I), and the SAR
      that determines which allocation of vaccine and placebo within households
      provides the most information. In general, individual randomization with a mixed
      allocation of vaccine and placebo is better for estimating both VE(S) and VE(I)
      than is randomizing by household. However, for estimation of VE(I), at very low
      SARs and low VE(S), randomization by household is slightly more efficient than
      randomization by individual.

PMID- 11315009
TI  - A condition for designing bus-route type access site surveys to estimate
      recreational fishing effort.
AB  - A theoretical framework for using bus-route surveys to estimate recreational
      fishing effort has been established by taking into account the arrival and
      departure distributions of the fishing parties. Properties of a fishing effort
      estimator proposed by Robson and Jones (1989) are investigated. It is found that
      the estimator is not automatically unbiased; rather, a condition on the survey
      design has to be satisfied in order to be unbiased. The condition is simple and
      can be easily implemented.

PMID- 11315010
TI  - A marginal mixed baseline hazards model for multivariate failure time data.
AB  - In multivariate failure time data analysis, a marginal regression modeling
      approach is often preferred to avoid assumptions on the dependence structure
      among correlated failure times. In this paper, a marginal mixed baseline hazards
      model is introduced. Estimating equations are proposed for the estimation of the
      marginal hazard ratio parameters. The proposed estimators are shown to be
      consistent and asymptotically Gaussian with a robust covariance matrix that can
      be consistently estimated. Simulation studies indicate the adequacy of the
      proposed methodology for practical sample sizes. The methodology is illustrated
      with a data set from the Framingham Heart Study.

PMID- 11315011
TI  - Modeling clustered, discrete, or grouped time survival data with covariates.
AB  - We have developed methods for modeling discrete or grouped time, right-censored
      survival data collected from correlated groups or clusters. We assume that the
      marginal hazard of failure for individual items within a cluster is specified by
      a linear log odds survival model and the dependence structure is based on a gamma
      frailty model. The dependence can be modeled as a function of cluster-level
      covariates. Likelihood equations for estimating the model parameters are
      provided. Generalized estimating equations for the marginal hazard regression
      parameters and pseudolikelihood methods for estimating the dependence parameters
      are also described. Data from two clinical trials are used for illustration
      purposes.

PMID- 11315012
TI  - Highly resistant regression and object matching.
AB  - In many disciplines, it is of great importance to match objects. Procrustes
      analysis is a popular method for comparing labeled point configurations based on
      a least squares criterion. We consider alternative procedures that are highly
      resistant to outlier points, and we describe an application in electrophoretic
      gel matching. We consider procedures based on S estimators, least median of
      squares, and least quartile difference estimators. Practical implementation
      issues are discussed, including random subset selection and intelligent subset
      selection (where subsets with small size or near collinear subsets are ignored).
      The relative performances of the resistant and Procrustes methods are examined in
      a simulation study.

PMID- 11315013
TI  - Fitting the log-F accelerated failure time model with incomplete covariate data.
AB  - Data obtained from studies in the health sciences often have incompletely
      observed covariates as well as censored outcomes. In this paper, we present
      methods for fitting the log-F accelerated failure time model with incomplete
      continuous and/or categorical time-independent covariates using the Gibbs
      sampler. A general location model that allows different covariance structures
      across cells is specified for the covariates, and ignorable missingness of the
      covariates is assumed. Techniques that accommodate standard assumptions of
      ignorable censoring as well as certain types of nonignorable censoring are
      developed. We compare our approach to traditional complete-case analysis in an
      application to data obtained from a study of melanoma. The comparison indicates
      that substantial gains in efficiency are possible with our approach.

PMID- 11315014
TI  - Testing for age-at-onset anticipation with affected parent-child pairs.
AB  - The tendency for the onset of a genetic disease to occur at progressively earlier
      ages or with progressively greater severity in successive generations is known as
      anticipation. Following the discovery of trinucleotide repeat expansion as a
      plausible genetic mechanism for anticipation, interest in testing for
      anticipation has increased. Studies of anticipation can be biased when parents
      with late onset or children with early onset are preferentially ascertained. This
      paper presents a nonparametric approach to testing for age-at-onset anticipation
      that adjusts for such preferential ascertainment. The approach is illustrated
      through application to data on panic disorder.

PMID- 11315015
TI  - Estimating equations for a latent transition model with multiple discrete
      indicators.
AB  - This paper proposes a two-part model for studying transitions between health
      states over time when multiple, discrete health indicators are available. The
      includes a measurement model positing underlying latent health states and a
      transition model between latent health states over time. Full maximum likelihood
      estimation procedures are computationally complex in this latent variable
      framework, making only a limited class of models feasible and estimation of
      standard errors problematic. For this reason, an estimating equations analogue of
      the pseudo-likelihood method for the parameters of interest, namely the
      transition model parameters, is considered. The finite sample properties of the
      proposed procedure are investigated through a simulation study and the importance
      of choosing strong indicators of the latent variable is demonstrated. The
      applicability of the methodology is illustrated with health survey data measuring
      disability in the elderly from the Longitudinal Study of Aging.

PMID- 11315016
TI  - Statistical quality control of variety trial data.
AB  - I propose detection criteria for identifying an abnormal or erroneous data vector
      provided by a single variety trial in a longer series of variety trials. The test
      criteria are based on the linear effects estimated separately for each studied
      trial using global variance components estimated from the whole series of variety
      trials. The criteria comprise three mutually independent test statistics. The
      first one is a quadratic form in the estimated fixed effects, the second one is a
      quadratic form in the estimated realized linear random effects not including the
      residual effects, and the third one is a quadratic form in the estimated realized
      residual effects. Under the null hypothesis defining a valid data vector, the
      three quadratics have independent chi2 distributions. Under natural alternative
      hypotheses, they have noncentral chi2 distributions. Decomposing the total
      variation of the data vector studied into quadratic forms due to different types
      of the realized linear effects intuitively justifies the resulting test criteria.
      The decomposition may also be used to show that the resulting tests are
      likelihood ratio tests. I further present computational procedures that allow us
      to dispense with the need for prior estimation of the linear effects.

PMID- 11315017
TI  - Modification of sample size in group sequential clinical trials.
AB  - In group sequential clinical trials, sample size reestimation can be a
      complicated issue when it allows for change of sample size to be influenced by an
      observed sample path. Our simulation studies show that increasing sample size
      based on an interim estimate of the treatment difference can substantially
      inflate the probability of type I error in most practical situations. A new group
      sequential test procedure is developed by modifying the weights used in the
      traditional repeated significance two-sample mean test. The new test has the type
      I error probability preserved at the target level and can provide a substantial
      gain in power with the increase of sample size. Generalization of the new
      procedure is discussed.

PMID- 11315018
TI  - A Bayesian hierarchical approach for combining case-control and prospective
      studies.
AB  - Motivated by the absolute risk predictions required in medical decision making
      and patient counseling, we propose an approach for the combined analysis of case
      control and prospective studies of disease risk factors. The approach is
      hierarchical to account for parameter heterogeneity among studies and among
      sampling units of the same study. It is based on modeling the retrospective
      distribution of the covariates given the disease outcome, a strategy that greatly
      simplifies both the combination of prospective and retrospective studies and the
      computation of Bayesian predictions in the hierarchical case-control context.
      Retrospective modeling differentiates our approach from most current strategies
      for inference on risk factors, which are based on the assumption of a specific
      prospective model. To ensure modeling flexibility, we propose using a mixture
      model for the retrospective distributions of the covariates. This leads to a
      general nonlinear regression family for the implied prospective likelihood. After
      introducing and motivating our proposal, we present simple results that highlight
      its relationship with existing approaches, develop Markov chain Monte Carlo
      methods for inference and prediction, and present an illustration using ovarian
      cancer data.

PMID- 11315019
TI  - Dual screening.
AB  - We discuss the problem of screening a general population for characteristics such
      as HIV or drug use. Our main approach is Bayesian, which allows for the
      incorporation of prior information about parameters. In the particular problem we
      consider, there is currently no information in the data for estimating the
      sensitivity of the screening test, and consequently, the prevalence of the
      characteristic among screened negatives cannot be estimated from the collected
      data alone. Our inferences are straightforward to obtain using Gibbs sampling
      techniques, and they are valid for large or small samples and for arbitrary
      prevalence or accuracy of screening tests. We also develop the maximum-likelihood
      approach using the EM algorithm.

PMID- 11315020
TI  - A unifying family of group sequential test designs.
AB  - Currently, the design of group sequential clinical trials requires choosing among
      several distinct design categories, design scales, and strategies for determining
      stopping rules. This approach can limit the design selection process so that
      clinical issues are not fully addressed. This paper describes a family of designs
      that unifies previous approaches and allows continuous movement among the
      previous categories. This unified approach facilitates the process of tailoring
      the design to address important clinical issues. The unified family of designs is
      constructed from a generalization of a four-boundary group sequential design in
      which the shape and location of each boundary can be independently specified.
      Methods for implementing the design using error-spending functions are described.
      Examples illustrating the use of the design family are also presented.

PMID- 11315021
TI  - Efficiency robust tests for survival or ordered categorical data.
AB  - The selection of a single method of analysis is problematic when the data could
      have been generated by one of several possible models. We examine the properties
      of two tests designed to have high power over a range of models. The first one,
      the maximum efficiency robust test (MERT), uses the linear combination of the
      optimal statistics for each model that maximizes the minimum efficiency. The
      second procedure, called the MX, uses the maximum of the optimal statistics. Both
      approaches yield efficiency robust procedures for survival analysis and ordinal
      categorical data. Guidelines for choosing between them are provided.

PMID- 11315022
TI  - A penalized likelihood approach for a progressive three-state model with censored
      and truncated data: application to AIDS.
AB  - We consider the estimation of the intensity and survival functions for a
      continuous time progressive three-state semi-Markov model with intermittently
      observed data. The estimator of the intensity function is defined
      nonparametrically as the maximum of a penalized likelihood. We thus obtain smooth
      estimates of the intensity and survival functions. This approach can accommodate
      complex observation schemes such as truncation and interval censoring. The method
      is illustrated with a study of hemophiliacs infected by HIV. The intensity
      functions and the cumulative distribution functions for the time to infection and
      for the time to AIDS are estimated. Covariates can easily be incorporated into
      the model.

PMID- 11315023
TI  - Standard errors of heritabilities for forage breeding nurseries.
AB  - Estimators for standard errors of heritability for two typical and complex forage
      breeding models are illustrated with estimates of variance and covariance
      components from least-squares and restricted maximum likelihood methods. The
      first experiment (Model 1) is a factorial design (two grazing management factors)
      with two layers of split plots (populations and grazing periods) and with plants
      within populations nested beneath the first split. The second model is for a
      sites pooling of randomized complete block experiments, with plants nested inside
      plots and with a split in time. One definition of heritability was applied to the
      plant habit character for both models in a red clover germplasm. Heritability
      estimates were statistically the same for the two methods for both models.

PMID- 11315024
TI  - Assessing distributions of estimated drug shelf lives in stability analysis.
AB  - A stability study is usually conducted to ensure that a drug product can meet the
      approved specifications prior to its expiration dating period (shelf life).
      Several approaches for determination of drug shelf life assuming random batches
      have been proposed. In this paper, we examine sampling distributions of the
      estimated shelf lives proposed by Shao and Chow (1994, Biometrics 50, 753-763).
      An application to some stability data from the pharmaceutical industry is
      presented.

PMID- 11315025
TI  - Estimating equations for parameters in stochastic growth models from tag
      recapture data.
AB  - James (1991, Biometrics 47, 1519-1530) constructed unbiased estimating functions
      for estimating the two parameters in the von Bertalanffy growth curve from tag
      recapture data. This paper provides unbiased estimating functions for a class of
      growth models that incorporate stochastic components and explanatory variables. A
      simulation study using seasonal growth models indicates that the proposed method
      works well while the least-squares methods that are commonly used in the
      literature may produce substantially biased estimates. The proposed model and
      method are also applied to real data from tagged rock lobsters to assess the
      possible seasonal effect on growth.

PMID- 11315026
TI  - Estimation of population size based on additive hazards models for continuous
      time recapture experiments.
AB  - We use the semiparametric additive hazards model to formulate the effects of
      individual covariates on the capture rates in the continuous-time capture
      recapture experiment, and then construct a Horvitz-Thompson-type estimator for
      the unknown population size. The resulting estimator is consistent and
      asymptotically normal with an easily estimated variance. Simulation studies show
      that the asymptotic approximations are adequate for practical use when the
      average capture probabilities exceed .5. Ignoring covariates would underestimate
      the population size and the coverage probability is poor. A wildlife example is
      provided.

PMID- 11315027
TI  - Regression analysis of doubly censored failure time data with applications to
      AIDS studies.
AB  - In many epidemiological studies, the survival time of interest is the elapsed
      time between two related events, the originating event and the failure event, and
      the times of the occurrences of both events are right or interval censored. We
      discuss the regression analysis of such studies and a simple estimating equation
      approach is proposed under the proportional hazards model. The method can easily
      be implemented and does not involve any iteration among unknown parameters, as
      full likelihood approaches proposed in the literature do. The asymptotic
      properties of the proposed regression coefficient estimates are derived and an
      AIDS cohort study is analyzed to illustrate the proposed approach.

PMID- 11315028
TI  - A mixed model for two-state Markov processes under panel observation.
AB  - Many chronic medical conditions can be meaningfully characterized in terms of a
      two-state stochastic process. Here we consider the problem in which subjects make
      transitions among two such states in continuous time but are only observed at
      discrete, irregularly spaced time points that are possibly unique to each
      subject. Data arising from such an observation scheme are called panel data, and
      methods for related analyses are typically based on Markov assumptions. The
      purpose of this article is to present a conditionally Markov model that
      accommodates subject-to-subject variation in the model parameters by the
      introduction of random effects. We focus on a particular random effects
      formulation that generates a closed-form expression for the marginal likelihood.
      The methodology is illustrated by application to a data set from a parasitic
      field infection survey.

PMID- 11315029
TI  - Exact inference for growth curves with intraclass correlation structure.
AB  - We consider repeated observations taken over time for each of several subjects.
      For example, one might consider the growth curve of a cohort of babies over time.
      We assume a simple linear growth curve model. Exact results based on sufficient
      statistics (exact tests of the null hypothesis that a coefficient is zero, or
      exact confidence intervals for coefficients) are not available to make inference
      on regression coefficients when an intraclass correlation structure is assumed.
      This paper will demonstrate that such exact inference is possible using
      generalized inference.

PMID- 11315030
TI  - Optimal designs when the variance is a function of the mean.
AB  - We develop locally D-optimal designs for nonlinear models when the variance of
      the response is a function of its mean. Using the two-parameter Michaelis-Menten
      model as an example, we show that the optimal design depends on both the type of
      heteroscedasticity and the magnitude of the variation. In addition, our results
      suggest that the homoscedastic D-optimal design has high efficiency under a broad
      class of heteroscedastic patterns and that it is fairly insensitive to nominal
      values of the parameters.

PMID- 11315031
TI  - Modeling daily and subdaily cycles in rat sleep data.
AB  - We developed a statistical model for rat sleep-wake behavior over the 24-hour
      day; this model could be used for animals exposed to shorter cycles of light and
      dark conditions. Rat behavior was classified either as "wake" or "sleep," as
      determined by analysis of electrophysiological data. The proposed model consists
      of three parts: the first two explain cyclic effects relating to the lighting
      conditions, whereas the last part reflects any acyclic effect. Hypothesis tests
      were conducted on the magnitude of the parts. The model also accounts for
      correlated errors.

PMID- 11315032
TI  - Modeling a categorical variable allowing arbitrarily many category choices.
AB  - This article discusses the modeling of a categorical variable for which subjects
      can select any number of categories. For c categories, the response variable
      consists of a cross-classification of c binary components, one pertaining to each
      category. Using data from a survey (Loughin, T. M. and Scherer, P. N., 1998,
      Biometrics, 54, 630 637) in which Kansas farmers indicated their primary sources
      of veterinary information, we discuss simultaneous logit modeling of the binary
      components of the multivariate response. The use of maximum likelihood or quasi
      likelihood fitting provides chi-squared tests with degrees of freedom df = c(r -
      1) for testing the independence between each of the c response components and an
      explanatory variable with r categories. These tests are alternatives to the
      weighted chi-squared test and the bootstrap test proposed by Loughin and Scherer
      for this hypothesis.

PMID- 11315033
TI  - Prediction using partly conditional time-varying coefficients regression models.
AB  - Data collected longitudinally in time provide the opportunity to develop
      predictive models of future observations given current data for an individual.
      Such models may be of particular value in defining individuals at high risk and
      thereby in suggesting subgroups for targeting of prevention intervention research
      efforts. In this paper, we propose a method for estimating predictive functions.
      The method uses an extension of the marginal regression analysis methods of Liang
      and Zeger (1986, Biometrika 73, 13-22) and is implemented using simple estimating
      equations. A key feature of the models is that regression coefficients are
      modelled as smooth functions of the times both at and for prediction. Data from a
      study of obesity in childhood and early adulthood is used to demonstrate the
      methodology. Criteria for defining individuals to be at high risk can be defined
      on the basis of estimated predictive functions. We suggest methods for evaluating
      the diagnostic accuracy (sensitivity and specificity) of such rules using cross
      validation. The method holds promise as a robust and technically easy way of
      evaluating information about future prognosis that may be gleaned from a
      patient's current and past clinical status.

PMID- 11315034
TI  - An application of isotonic longitudinal marginal regression to monitoring the
      healing process.
AB  - This paper discusses marginal regression for repeated ordinal measurements that
      are isotonic over time. Such data are often observed in longitudinal studies on
      healing processes in which, due to recovery, the status of patients only improves
      or remains the same. We show how this prior information can be used to construct
      appropriate and parsimoniously parametrized marginal models. As a second aspect,
      we also incorporate nonparametric fitting of covariate effects via a penalized
      quasi-likelihood or general estimating equation approach. We illustrate our
      methods by an application to sports-related injuries.

PMID- 11315035
TI  - Relating the classical covariance adjustment techniques of multivariate growth
      curve models to modern univariate mixed effects models.
AB  - The relationship between the modern univariate mixed model for analyzing
      longitudinal data, popularized by Laird and Ware (1982, Biometrics 38, 963-974),
      and its predecessor, the classical multivariate growth curve model, summarized by
      Grizzle and Allen (1969, Biometrics 25, 357-381), has never been clearly
      established. Here, the link between the two methodologies is derived, and
      balanced polynomial and cosinor examples cited in the literature are analyzed
      with both approaches. Relating the two models demonstrates that classical
      covariance adjustment for higher-order terms is analogous to including them as
      random effects in the mixed model. The polynomial example clearly illustrates the
      relationship between the methodologies and shows their equivalence when all
      matrices are properly defined. The cosinor example demonstrates how results from
      each method may differ when the total variance-covariance matrix is positive
      definite, but that the between-subjects component of that matrix is not so
      constrained by the growth curve approach. Additionally, advocates of each
      approach tend to consider different covariance structures. Modern mixed model
      analysts consider only those terms in a model's expectation (or linear
      combinations), and preferably the most parsimonious subset, as candidates for
      random effects. Classical growth curve analysts automatically consider all terms
      in a model's expectation as random effects and then investigate whether
      "covariance adjusting" for higher-order terms improves the model. We apply mixed
      model techniques to cosinor analyses of a large, unbalanced data set to
      demonstrate the relevance of classical covariance structures that were previously
      conceived for use only with completely balanced data.

PMID- 11315036
TI  - Modeling tumor onset and multiplicity using transition models with latent
      variables.
AB  - We describe a method for modeling carcinogenicity from animal studies where the
      data consist of counts of the number of tumors present over time. The research is
      motivated by applications to transgenic rodent studies, which have emerged as an
      alternative to chronic bioassays for screening possible carcinogens. In
      transgenic mouse studies, the endpoint of interest is frequently skin papilloma,
      with weekly examinations determining how many papillomas each animal has at a
      particular point in time. It is assumed that each animal has two unobservable
      latent variables at each time point. The first indicates whether or not the
      tumors are in a multiplying state and the second is the potential number of
      additional tumors if the tumors are in a multiplying state. The product of these
      variables follows a zero-inflated Poisson distribution, and the EM algorithm can
      be used to maximize the observed-data pseudo-likelihood, based on the latent
      variables. A generalized estimating equations robust variance estimator adjusts
      for dependency among outcomes within individual animals. The method is applied to
      testing for a dose-related trend in both tumor incidence and multiplicity in
      carcinogenicity studies.

PMID- 11315037
TI  - Decision theoretic designs for phase II clinical trials with multiple outcomes.
AB  - In many phase II clinical trials, it is essential to assess both efficacy and
      safety. Although several phase II designs that accommodate multiple outcomes have
      been proposed recently, none are derived using decision theory. This paper
      describes a Bayesian decision theoretic strategy for constructing phase II
      designs based on both efficacy and adverse events. The gain function includes
      utilities assigned to patient outcomes, a reward for declaring the new treatment
      promising, and costs associated with the conduct of the phase II trial and future
      phase III testing. A method for eliciting gain function parameters from medical
      collaborators and for evaluating the design's frequentist operating
      characteristics is described. The strategy is illustrated by application to a
      clinical trial of peripheral blood stem cell transplantation for multiple
      myeloma.

PMID- 11315038
TI  - Selection models and pattern-mixture models for incomplete data with covariates.
AB  - Most models for incomplete data are formulated within the selection model
      framework. This paper studies similarities and differences of modeling incomplete
      data within both selection and pattern-mixture settings. The focus is on missing
      at random mechanisms and on categorical data. Point and interval estimation is
      discussed. A comparison of both approaches is done on side effects in a
      psychiatric study.

PMID- 11315039
TI  - Estimating equations with nonignorably missing response data.
AB  - Troxel, Lipsitz, and Brennan (1997, Biometrics 53, 857-869) considered parameter
      estimation from survey data with nonignorable nonresponse and proposed weighted
      estimating equations to remove the biases in the complete-case analysis that
      ignores missing observations. This paper suggests two alternative modifications
      for unbiased estimation of regression parameters when a binary outcome is
      potentially observed at successive time points. The weighting approach of Robins,
      Rotnitzky, and Zhao (1995, Journal of the American Statistical Association 90,
      106-121) is also modified to obtain unbiased estimating functions. The suggested
      estimating functions are unbiased only when the missingness probability is
      correctly specified, and misspecification of the missingness model will result in
      biases in the estimates. Simulation studies are carried out to assess the
      performance of different methods when the covariate is binary or normal. For the
      simulation models used, the relative efficiency of the two new methods to the
      weighting methods is about 3.0 for the slope parameter and about 2.0 for the
      intercept parameter when the covariate is continuous and the missingness
      probability is correctly specified. All methods produce substantial biases in the
      estimates when the missingness model is misspecified or underspecified. Analysis
      of data from a medical survey illustrates the use and possible differences of
      these estimating functions.

PMID- 11315040
TI  - Useful methods for sensitivity analysis of observational studies.

PMID- 11315041
TI  - A new approach to modeling daily probabilities of conception.
AB  - Standard conception probabilities models assume that different acts of
      intercourse make independent contributions to the probability of conception in
      viable cycles. We propose an alternative, approximate model based on the
      assumption that the act of intercourse closest to the time of maximum fertility
      is the one most likely to have caused conception. We describe an adaptive
      algorithm [the most fertile intercourse day (MFID) algorithm] that estimates the
      most fertile intercourse day in each cycle. The approach is easily extended to
      include covariates and random between-couple differences in fecundability that
      affect the probability of conception in a given cycle. Reanalyses of two data
      sets reported in the literature are presented. Estimates of the probability of
      conception during the most fertile period of the cycle and of the effects of
      covariates are similar to estimates found using standard models.

PMID- 11315042
TI  - The stratified Petersen estimator with a known number of unread tags.
AB  - The Petersen estimator estimator of abundance can be biased when the assumption
      of homogeneous capture probability or homogeneous recapture probability is
      violated. Often this heterogeneity is related to the time or place of capture or
      recapture, and if these can be stratified, the stratified Petersen estimator
      reduces the bias caused by this heterogeneity. In some experiments, not all the
      recovered tagged animals can be examined, and only a subsample has its stratum of
      release and recovery determined. We develop methods for this modified experiment
      and apply them to estimate the number of salmon returning to spawn in a river in
      British Columbia, Canada.

PMID- 11315043
TI  - Empirical Bayes estimation of random effects parameters in mixed effects logistic
      regression models.
AB  - We extend an approach for estimating random effects parameters under a random
      intercept and slope logistic regression model to include standard errors, thereby
      including confidence intervals. The procedure entails numerical integration to
      yield posterior empirical Bayes (EB) estimates of random effects parameters and
      their corresponding posterior standard errors. We incorporate an adjustment of
      the standard error due to Kass and Steffey (KS; 1989, Journal of the American
      Statistical Association 84, 717-726) to account for the variability in estimating
      the variance component of the random effects distribution. In assessing health
      care providers with respect to adult pneumonia mortality, comparisons are made
      with the penalized quasi-likelihood (PQL) approximation approach of Breslow and
      Clayton (1993, Journal of the American Statistical Association 88, 9-25) and a
      Bayesian approach. To make comparisons with an EB method previously reported in
      the literature, we apply these approaches to crossover trials data previously
      analyzed with the estimating equations EB approach of Waclawiw and Liang (1994,
      Statistics in Medicine 13, 541-551). We also perform simulations to compare the
      proposed KS and PQL approaches. These two approaches lead to EB estimates of
      random effects parameters with similar asymptotic bias. However, for many
      clusters with small cluster size, the proposed KS approach does better than the
      PQL procedures in terms of coverage of nominal 95% confidence intervals for
      random effects estimates. For large cluster sizes and a few clusters, the PQL
      approach performs better than the KS adjustment. These simulation results agree
      somewhat with those of the data analyses.

PMID- 11315044
TI  - Likelihood-based experimental design for estimation of ED50.
AB  - In selecting the best dosage choice for the estimation of ED50, it is natural to
      try to minimize the length of the confidence intervals. In this presentation, the
      dose allocation that minimizes the length of the likelihood-based confidence
      intervals is presented and compared with alternative allocations that have been
      proposed based on the length of different types of confidence intervals, such as
      those based on the asymptotic variance or on Fieller's Theorem. Effective
      strategies to deal with the parameter dependence of these allocations are
      explored. A series of experiments to evaluate the effect of small doses per
      fraction on the radiation tolerance of the rat cervical spinal cord provide the
      motivation and an illustration for the proposed procedures.

PMID- 11315045
TI  - Empirical Bayes estimation for combinations of multivariate bioassays.
AB  - This article presents a new empirical Bayes estimator (EBE) and a shrinkage
      estimator for determining the relative potency from several multivariate
      bioassays by incorporating prior information on the model parameters based on
      Jeffreys' rules. The EBE can account for any extra variability among the
      bioassays, and if this extra variability is 0, then the EBE reduces to the
      maximum likelihood estimator for combinations of multivariate bioassays. The
      shrinkage estimator turns out to be a compromise of the prior information and the
      estimator from each multivariate bioassay, with the weights depending on the
      prior variance.

PMID- 11315046
TI  - Minimally selected p and other tests for a single abrupt changepoint in a binary
      sequence.
AB  - A novel changepoint statistic based on the minimum value, over possible
      changepoint locations, of Fisher's Exact Test, is introduced. Specific points in
      the exact distribution of the minimally selected Fisher's value may be rapidly
      calculated as a lattice-path counting problem via known recurrence methods. The
      test is compared to the Kolmogorov-Smirnov two-sample test, the maximally
      selected chi-square, and a likelihood ratio test. The tests are applied to
      assessing recombination in genetic sequences of HIV.

PMID- 11315047
TI  - Multitype spatial point patterns with hierarchical interactions.
AB  - Multitype spatial point patterns with hierarchical interactions are considered.
      Here hierarchical interaction means directionality: points on a higher level of
      hierarchy affect the locations of points on the lower levels, but not vice versa.
      Such relations are common, for example, in ecological communities. Interacting
      point patterns are often modeled by Gibbs processes with pairwise interactions.
      However, these models are inherently symmetric, and the hierarchy can be
      acknowledged only when interpreting the results. We suggest the following in
      allowing the inclusion of the hierarchical structure in the model. Instead of
      regarding the pattern as a realization of a stationary multivariate point
      process, we build the pattern one type at a time according to the order of the
      hierarchy by using nonstationary univariate processes. As interactions connected
      to points x on a certain level are considered, the effect of the higher levels is
      interpreted as heterogeneity of the pattern x, and the points on the lower levels
      are neglected because of the hierarchical structure.

PMID- 11315048
TI  - Analysis of experimental data with repeated measurements.
AB  - Experimental data often consist of serial measurements on subjects after a
      treatment. Typical questions concerning such data are: (A) Do subjects really
      react to treatment or are the fluctuations just random? (B) What are the
      numerical characteristics of the response? (C) Is the response identical in all
      groups? Differences between the individuals in the dynamics of the reaction make
      it difficult to apply standard statistical procedures. This paper proposes to
      answer questions (A) and (B) at the individual level, then to give an answer to
      (C) on the basis of this information. This kind of analysis may be useful since
      it can separate subjects giving response from those that do not and can identify
      individual response patterns and compare treatments with respect to each
      numerical characteristic separately. To answer question (A), a permutation test
      is proposed and its power is evaluated by simulation.

PMID- 11315049
TI  - Improved error bounds for genetic distances from DNA sequences.
AB  - The genetic distance between two DNA sequences may be measured by the average
      number of nucleotide substitutions per position that has occurred since the two
      sequences diverged from a common ancestor. Estimates of this quantity can be
      derived from Markov models for the substitution process, while the variances are
      estimated using the delta method and confidence intervals calculated assuming
      normality. However, when the sampling distribution of the estimator deviates from
      normality, such intervals will not be accurate. For simple one-parameter models
      of nucleotide substitution, we propose a transformation of normal confidence
      intervals, which yields an almost exact approximation to the true confidence
      intervals of the distance estimators. To calculate confidence intervals for more
      complicated models, we propose the saddlepoint approximation. A simulation study
      shows that the saddlepoint-derived confidence intervals are a real improvement
      over existing methods.

PMID- 11315050
TI  - Bayesian survival analysis using a MARS model.
AB  - A Bayesian multivariate adaptive regression spline fitting approach is used to
      model univariate and multivariate survival data with censoring. The possible
      models contain the proportional hazards model as a subclass and automatically
      detect departures from this. A reversible jump Markov chain Monte Carlo algorithm
      is described to obtain the estimate of the hazard function as well as the
      survival curve.

PMID- 11315051
TI  - Estimating regression parameters and degree of dependence for multivariate
      failure time data.
AB  - Multivariate failure time data are frequently encountered in longitudinal studies
      when subjects may experience several events or when there is a grouping of
      individuals into a cluster. To take into account the dependence of the failure
      times within the unit (the individual or the cluster) as well as censoring, two
      multivariate generalizations of the Cox proportional hazards model are commonly
      used. The marginal hazard model is used when the purpose is to estimate mean
      regression parameters, while the frailty model is retained when the purpose is to
      assess the degree of dependence within the unit. We propose a new approach based
      on the combination of the two aforementioned models to estimate both these
      quantities. This two-step estimation procedure is quicker and more simple to
      implement than the EM algorithm used in frailty models estimation. Simulation
      results are provided to illustrate robustness, consistency, and large-sample
      properties of estimators. Finally, this method is exemplified on a diabetic
      retinopathy study in order to assess the effect of photocoagulation in delaying
      the onset of blindness as well as the dependence between the two eyes blindness
      times of a patient.

PMID- 11315052
TI  - Sequential methods for comparing years of life saved in the two-sample censored
      data problem.
AB  - This research develops nonparametric strategies for sequentially monitoring
      clinical trial data where detecting years of life saved is of interest. The
      recommended test statistic looks at integrated differences in survival estimates
      during the time frame of interest. In many practical situations, the test
      statistic presented has an independent increments covariance structure. Hence,
      with little additional work, we may apply these testing procedures using
      available methodology. In the case where an independent increments covariance
      structure is present, we suggest how clinical trial data might be monitored using
      these statistics in an information-based design. The resulting study design
      maintains the desired stochastic operating characteristics regardless of the
      shapes of the survival curves being compared. This offers an advantage over the
      popular log-rank-based design strategy since more restrictive assumptions
      relating to the behavior of the hazards are required to guarantee the planned
      power of the test. Recommendations for how to sequentially monitor clinical trial
      progress in the nonindependent increments case are also provided along with an
      example.

PMID- 11315053
TI  - Confidence bands for cumulative incidence curves under the additive risk model.
AB  - In the context of competing risks, the cumulative incidence function is often
      used to summarize the cause-specific failure-time data. As an alternative to the
      proportional hazards model, the additive risk model is used to investigate
      covariate effects by specifying that the subject-specific hazard function is the
      sum of a baseline hazard function and a regression function of covariates. Based
      on such a formulation, we present an approach to constructing simultaneous
      confidence intervals for the cause-specific cumulative incidence function of
      patients with given risk factors. A melanoma data set is used for the purpose of
      illustration.

PMID- 11315054
TI  - Efficient estimation of the distribution of quality-adjusted survival time.
AB  - Quality of life is an important aspect in evaluation of clinical trials of
      chronic diseases, such as cancer and AIDS. Quality-adjusted survival analysis is
      a method that combines both the quantity and quality of a patient's life into one
      single measure. In this paper, we discuss the efficiency of weighted estimators
      for the distribution of quality-adjusted survival time. Using the general
      representation theorem for missing data processes, we are able to derive an
      estimator that is more efficient than the one proposed in Zhao and Tsiatis (1997,
      Biometrika 84, 339-348). Simulation experiments are conducted to assess the small
      sample properties of this estimator and to compare it with the semiparametric
      efficiency bound. The value of this estimator is demonstrated from an application
      of the method to a data set obtained from a breast cancer clinical trial.

PMID- 11315055
TI  - The two-sample problem with induced dependent censorship.
AB  - Induced dependent censorship is a general phenomenon in health service evaluation
      studies in which a measure such as quality-adjusted survival time or lifetime
      medical cost is of interest. We investigate the two-sample problem and propose
      two classes of nonparametric tests. Based on consistent estimation of the
      survival function for each sample, the two classes of test statistics examine the
      cumulative weighted difference in hazard functions and in survival functions. We
      derive a unified asymptotic null distribution theory and inference procedure. The
      tests are applied to trial V of the International Breast Cancer Study Group and
      show that long duration chemotherapy significantly improves time without symptoms
      of disease and toxicity of treatment as compared with the short duration
      treatment. Simulation studies demonstrate that the proposed tests, with a wide
      range of weight choices, perform well under moderate sample sizes.

PMID- 11315056
TI  - Normal approximation diagnostics for the Cox model.
AB  - We discuss two diagnostic methods for assessing the accuracy of the normal
      approximated confidence region to the likelihood-based confidence region for the
      Cox proportional hazards model with censored data. The proposed diagnostic
      methods are extensions of the contour measures of Hodges (1987, Journal of the
      American Statistical Association 82, 149-154) and Cook and Tsai (1990, Journal of
      the American Statistical Association 85, 770-777) and the curvature measures of
      Jennings (1986, Journal of the American Statistical Association 81, 471-476) and
      Cook and Tsai (1990). These methods are also illustrated in a study of hepatocyte
      growth factor in patients with lung cancer and a Mayo Clinic randomized study of
      participants with primary biliary cirrhosis.

PMID- 11315057
TI  - Fitting a regression model for genotype-by-environment data on heading dates in
      grasses by methods for nonlinear mixed models.
AB  - The analysis of agricultural crop variety trials is usually complicated by the
      presence of genotype-by-environment interaction. A number of methods and models
      have been proposed to tackle this problem. One of the most common methods is the
      regression approach due to Yates and Cochran (1938, Journal of Agricultural
      Science 28, 556-580), in which performances of genotypes in the environments are
      regressed onto environmental means. The underlying regression model contains a
      multiplicative term with two unknown parameters (one for genotypes and one for
      environments). In the present paper, the model is modified by exchanging the role
      of genotypes and environments. Various diagnostic plots show that this modified
      model is adequate for a data set on heading dates in the grass species Dactylis
      glomerata. If environments are considered as a random factor while genotypes are
      taken as fixed, the model falls into the class of nonlinear mixed models.
      Recently, a number of procedures have been suggested for this class of models,
      which are based on first-order Taylor series expansion. Alternatively, the model
      can be estimated by maximum likelihood. This paper discusses the application of
      these methods for estimating parameters of the model.

PMID- 11315058
TI  - Ascertainment bias in rate ratio estimation from case-sibling control studies of
      variable age-at-onset diseases.
AB  - Motivated by a Finnish case-control study of early onset diabetes in which
      diabetic children are matched to sibling controls, we investigate ascertainment
      bias of the usual rate ratio estimator from case-control data under simplex
      complete ascertainment of families during a fixed interval of time. Analytic
      results indicate that the assumptions necessary for valid estimation are that the
      disease is rare and the factors under study are exchangeable--essentially that
      the covariate distribution does not depend on calendar time or birth order.
      Further, we found that the rare disease assumption could be dropped by
      restricting to cases that were diagnosed during the enrollment period of the
      study or including all cases but eliminating the proband as a control for non
      enrollment-period cases. An important consequence of this work is that standard
      family-based case-control studies are subject to ascertainment bias if
      exchangeability of the covariates under investigation does not hold.

PMID- 11315059
TI  - Two approaches for estimating disease prevalence from population-based registries
      of incidence and total mortality.
AB  - Two approaches are described for estimating the prevalence of a disease that may
      have developed in a previous restricted age interval among persons of a given age
      at a particular calendar time. The prevalence for all those who ever developed
      disease is treated as a special case. The counting method (CM) obtains estimates
      of prevalence by dividing the estimated number of diseased persons by the total
      population size, taking loss to follow-up into account. The transition rate
      method (TRM) uses estimates of transition rates and competing risk calculations
      to estimate prevalence. Variance calculations are described for CM and TRM as
      well as for a variant of CM, called counting method times 10 (CM10), that is
      designed to yield more precise estimates than CM. We compare these three
      estimators in terms of precision and in terms of the underlying assumptions
      required to justify the methods. CM makes fewer assumptions but is typically ess
      precise than TRM or CM10. For common diseases such as breast cancer, CM may be
      preferred because its precision is excellent even though not as high as for TRM
      or CM10. For less common diseases, such as brain cancer, however, TRM or CM10 and
      other methods that make stabilizing assumptions may be preferred to CM.

PMID- 11315060
TI  - Bayesian inference for prevalence in longitudinal two-phase studies.
AB  - We consider Bayesian inference and model selection for prevalence estimation
      using a longitudinal two-phase design in which subjects initially receive a low
      cost screening test followed by an expensive diagnostic test conducted on several
      occasions. The change in the subject's diagnostic probability over time is
      described using four mixed-effects probit models in which the subject-specific
      effects are captured by latent variables. The computations are performed using
      Markov chain Monte Carlo methods. These models are then compared using the
      deviance information criterion. The methodology is illustrated with an analysis
      of alcohol and drug use in adolescents using data from the Great Smoky Mountains
      Study.

PMID- 11315061
TI  - A multivariate test of interaction for use in clinical trials.
AB  - An important issue in clinical trials is whether the effect of treatment is
      essentially homogeneous as a function of baseline covariates. Covariates that
      have the potential for an interaction with treatment may be suspected on the
      basis of treatment mechanism or may be known risk factors, as it is often thought
      that the sickest patients may benefit most from treatment. If disease severity is
      more accurately determined by a collection of baseline covariates rather than a
      single risk factor, methods that examine each covariate in turn for interaction
      may be inadequate. We propose a procedure whereby treatment interaction is
      examined along a single severity index that is a linear combination of baseline
      covariates. Formally, we derive a likelihood ratio test based on the null beta0 =
      beta1 versus the alternative abeta0 = beta1, where X'beta(k) (k = 0, 1)
      corresponds to the severity index in arm k and X is a vector of baseline
      covariates. While our explicit test requires a Gaussian response, it can be
      readily implemented whenever the estimates of beta0,beta1 are approximately
      multivariate normal. For example, it is appropriate for large clinical trials
      where beta(k) is based on a logisitic or Cox regression of response on X.

PMID- 11315062
TI  - A class of permutation tests for stratified survival data.
AB  - We propose a class of permutation tests for stratified survival data. The tests
      are derived using the framework of Fay and Shih (1998, Journal of the American
      Statistical Association 93, 387-396), which creates tests by permuting scores
      based on a functional of estimated distribution functions. Here the estimated
      distribution function for each possibly right-, left-, or interval-censored
      observation is based on a shrinkage estimator similar to the nonparametric
      empirical estimator of Ghosh, Lahiri, and Tiwari (1989, Communications in
      Statistics--Theory and Methods 18, 121-146), and permutation is carried out
      within strata. The proposed test with a weighted Mann-Whitney functional is
      similar to the permutation form of the stratified log-rank test when there is a
      large strata effect or the sample size in each stratum is large and is similar to
      the permutation form of the ordinary log-rank test when there is little strata
      effect. Thus, the proposed test unifies the advantages of both the stratified and
      ordinary log-rank tests. By changing the functional, we may obtain a stratified
      Prentice-Wilcoxon test or a difference in means test with similar unifying
      properties. We show through simulations the advantage of the proposed test over
      existing tests for uncensored and right-censored data.

PMID- 11315063
TI  - Hierarchical proportional hazards regression models for highly stratified data.
AB  - In clinical trials conducted over several data collection centers, the most
      common statistically defensible analytic method, a stratified Cox model analysis,
      suffers from two important defects. First, identification of units that are
      outlying with respect to the baseline hazard is awkward since this hazard is
      implicit (rather than explicit) in the Cox partial likelihood. Second (and more
      seriously), identification of modest treatment effects is often difficult since
      the model fails to acknowledge any similarity across the strata. We consider a
      number of hierarchical modeling approaches that preserve the integrity of the
      stratified design while offering a middle ground between traditional stratified
      and unstratified analyses. We investigate both fully parametric (Weibull) and
      semiparametric models, the latter based not on the Cox model but on an extension
      of an idea by Gelfand and Mallick (1995, Biometrics 51, 843-852), which models
      the integrated baseline hazard as a mixture of monotone functions. We illustrate
      the methods using data from a recent multicenter AIDS clinical trial, comparing
      their ease of use, interpretation, and degree of robustness with respect to
      estimates of both the unit-specific baseline hazards and the treatment effect.

PMID- 11315064
TI  - Properties of a nonparametric test for early comparison of treatments in clinical
      trials in the presence of surrogate endpoints.
AB  - A nonparametric test is derived for comparing treatments with respect to the
      final endpoint in clinical trials in which the final endpoint has been observed
      for a random subset of patients, but results are available for a surrogate
      endpoint for a larger sample of patients. The test is an adaptation of the
      Wilcoxon-Mann-Whitney two-sample test, with an adjustment that involves a
      comparison of the ranks of the surrogate endpoints between patients with and
      without final endpoints. The validity of the test depends on the assumption that
      the patients with final endpoints represent a random sample of the patients
      registered in the study. This assumption is viable in trials in which the final
      endpoint is evaluated at a "landmark" timepoint in the patients' natural history.
      A small sample simulation study demonstrates that the test has a size that is
      close to the nominal value for all configurations evaluated. When compared with
      the conventional test based only on the final endpoints, the new test delivers
      substantial increases in power only when the surrogate endpoint is highly
      correlated with the true endpoint. Our research indicates that, in the absence of
      modeling assumptions, auxiliary information derived from surrogate endpoints can
      provide significant additional information only under special circumstances.

PMID- 11315065
TI  - Analysis of covariance with incomplete data via semiparametric model
      transformations.
AB  - We propose a method for fitting semiparametric models such as the proportional
      hazards (PH), additive risks (AR), and proportional odds (PO) models. Each of
      these semiparametric models implies that some transformation of the conditional
      cumulative hazard function (at each t) depends linearly on the covariates. The
      proposed method is based on nonparametric estimation of the conditional
      cumulative hazard function, forming a weighted average over a range of t-values,
      and subsequent use of least squares to estimate the parameters suggested by each
      model. An approximation to the optimal weight function is given. This allows
      semiparametric models to be fitted even in incomplete data cases where the
      partial likelihood fails (e.g., left censoring, right truncation). However, the
      main advantage of this method rests in the fact that neither the interpretation
      of the parameters nor the validity of the analysis depend on the appropriateness
      of the PH or any of the other semiparametric models. In fact, we propose an
      integrated method for data analysis where the role of the various semiparametric
      models is to suggest the best fitting transformation. A single continuous
      covariate and several categorical covariates (factors) are allowed. Simulation
      studies indicate that the test statistics and confidence intervals have good
      small-sample performance. A real data set is analyzed.

PMID- 11315066
TI  - Closed testing procedures for group sequential clinical trials with multiple
      endpoints.
AB  - A simple approach is given for conducting closed testing in clinical trials with
      multiple endpoints in which group sequential monitoring is planned. The approach
      allows a flexible stopping time; the earliest and latest stopping times are
      described. The paradigm is applicable both to clinical trials with multiple
      endpoints and to the one-sided multiple comparison problem of several treatments
      versus a control. The approach leads to enhancements of previous methods and
      suggestions for new methods. An example of a respiratory disease trial with four
      endpoints is given.

PMID- 11315067
TI  - Design of validation studies for estimating the odds ratio of exposure-disease
      relationships when exposure is misclassified.
AB  - We compared several validation study designs for estimating the odds ratio of
      disease with misclassified exposure. We assumed that the outcome and
      misclassified binary covariate are available and that the error-free binary
      covariate is measured in a subsample, the validation sample. We considered
      designs in which the total size of the validation sample is fixed and the
      probability of selection into the validation sample may depend on outcome and
      misclassified covariate values. Design comparisons were conducted for rare and
      common disease scenarios, where the optimal design is the one that minimizes the
      variance of the maximum likelihood estimator of the true log odds ratio relating
      the outcome to the exposure of interest. Misclassification rates were assumed to
      be independent of the outcome. We used a sensitivity analysis to assess the
      effect of misspecifying the misclassification rates. Under the scenarios
      considered, our results suggested that a balanced design, which allocates equal
      numbers of validation subjects into each of the four outcome/mismeasured
      covariate categories, is preferable for its simplicity and good performance. A
      user-friendly Fortran program is available from the second author, which
      calculates the optimal sampling fractions for all designs considered and the
      efficiencies of these designs relative to the optimal hybrid design for any
      scenario of interest.

PMID- 11315068
TI  - Test-based exact confidence intervals for the difference of two binomial
      proportions.
AB  - Confidence intervals are often provided to estimate a treatment difference. When
      the sample size is small, as is typical in early phases of clinical trials,
      confidence intervals based on large sample approximations may not be reliable. In
      this report, we propose test-based methods of constructing exact confidence
      intervals for the difference in two binomial proportions. These exact confidence
      intervals are obtained from the unconditional distribution of two binomial
      responses, and they guarantee the level of coverage. We compare the performance
      of these confidence intervals to ones based on the observed difference alone. We
      show that a large improvement can be achieved by using the standardized Z test
      with a constrained maximum likelihood estimate of the variance.

PMID- 11315069
TI  - Allometric extension.
AB  - Constants of allometric growth are commonly estimated by the first eigenvector of
      the covariance matrix of log measurements. Hills (1982, in Encyclopedia of
      Statistical Sciences, 48-54) defines a model of allometric extension for two
      related species by the conditions that (a) the constants of allometric growth are
      identical for both species and (b) the vector of mean differences is proportional
      to the common first eigenvector of both covariance matrices. We give a test for
      allometric extensionand discuss estimation of the parameters of the allometric
      extension model, including standard errors.

PMID- 11315070
TI  - Statistical inference for serial dilution assay data.
AB  - Serial dilution assays are widely employed for estimating substance
      concentrations and minimum inhibitory concentrations. The Poisson-Bernoulli model
      for such assays is appropriate for count data but not for continuous measurements
      that are encountered in applications involving substance concentrations. This
      paper presents practical inference methods based on a log-normal model and
      illustrates these methods using a case application involving bacterial toxins.

PMID- 11315071
TI  - On the equivalence of meta-analysis using literature and using individual patient
      data.
AB  - When data come from several independent studies for the purpose of estimating
      treatment control differences, meta-analysis can be carried out either on the
      best linear unbiased estimators computed from each study or on the pooled
      individual patient data modelled as a two-way model without interaction, where
      the two factors represent the different studies and the different treatments.
      Assuming that observations within and between studies are independent having a
      common variance, Olkin and Sampson (1998) have obtained the surprising result
      that the two meta-analytic procedures are equivalent, i.e., they both produce the
      same estimator. In this article, the same equivalence is established for the two
      way fixed-effects model without interaction with the only assumption that the
      observations across studies be independent. A consequence of the equivalence
      result is that, regardless of the covariance structure, it is possible to get an
      explicit representation for the best linear unbiased estimator of any vector of
      treatment contrasts in a two-way fixed-effects model without interaction as long
      as the studies are independent. Another interesting consequence is that, for the
      purpose of best linear unbiased estimation, an unbalanced two-way fixed-effects
      model without interaction can be treated as several independent unbalanced one
      way models, regardless of the covariance structure, when the studies are
      independent.

PMID- 11315072
TI  - Validating marker-based incidence estimates in repeatedly screened populations.
AB  - Disease incidence (new cases of disease per person per year) is usually measured
      by using longitudinal data. However, several recent proposals for measuring the
      incidence of human immunodeficiency virus (HIV) rely on cross-sectional data
      only. These methods assume each person is only sampled once; however, in some
      instances, it is necessary to consider these cross-sectional methods when
      individuals are represented more than once in the survey sample. We derive an
      extension of the cross-sectional incidence estimator that is valid for data from
      repeatedly screened populations and show under what conditions our new estimator
      reduces to the old estimator. An example involving estimation of HIV incidence
      among repeat blood donors is presented.

PMID- 11315073
TI  - Estimating the extent of tracking in interval-censored chain-of-events data.
AB  - This paper describes a method for determining whether the times between a chain
      of successive events (which all individuals experience in the same order) are
      correlated, for data in which the exact event times are not observed. Such data
      arise when individuals are only observed occasionally to determine which events
      have occurred. In such data, the (unknown) event times are interval censored. In
      addition, some individuals may have experienced some of the events before their
      first observation and may be lost to follow-up before experiencing the last
      event. Using a frailty model proposed by Aalen (1988, Mathematical Scientist 13,
      90-103) but which has never been used to analyze real data, we examine whether
      individuals who develop early markers of HIV infection can also be expected to
      develop antibody and other indicators of HIV infection more rapidly.

PMID- 11315074
TI  - Latent model for correlated binary data with diagnostic error.
AB  - We propose a methodology for modeling correlated binary data measured with
      diagnostic error. A shared random effect is used to induce correlations in
      repeated true latent binary outcomes and in observed responses and to link the
      probability of a true positive outcome with the probability of having a diagnosis
      error. We evaluate the performance of our proposed approach through simulations
      and compare it with an ad hoc approach. The methodology is illustrated with data
      from a study that assessed the probability of corneal arcus in patients with
      familial hypercholesterolemia.

PMID- 11315075
TI  - Nonparametric identification of the minimum effective dose.
AB  - We consider identifying the minimum effective dose (MED) in a dose-response
      study, where the MED is defined to be the lowest dose level producing an effect
      over that of the zero-dose control. Proposed herein is a nonparametric procedure
      based on the Mann-Whitney statistic incorporated with the step-down closed
      testing scheme. A numerical example demonstrates the feasibility of the proposed
      nonparametric procedure. Finally, the comparative results of a Monte Carlo level
      and power study for small sample sizes are presented and discussed.

PMID- 11315076
TI  - An exact test for all-way interaction in a 2M contingency table: application to
      interval capture-recapture estimation of population size.
AB  - An exact conditional test for an M-way log-linear interaction in a fully observed
      2M contingency table is formulated. From this is derived a procedure for interval
      estimation of the total count N in a 2M contingency table, one of whose entries
      is unobserved. This procedure has an immediate application to interval estimation
      of the size of a closed population from incomplete, overlapping lists of records,
      as in capture-recapture analysis of epidemiological data. Data on the prevalence
      of spina bifida in live births in upstate New York in 1969-1974 illustrate this
      application.

PMID- 11315077
TI  - Binary regression for risks in excess of subject-specific thresholds.
AB  - We describe models for binary valued data to be used to explain the incidence of
      disease given the level of a known risk factor. Every individual has an
      unobservable tolerance of the risk. Risk levels below the individual tolerance do
      not increase the disease incidence above the background, unexposed rate. We
      estimate parameters from both the tolerance distribution and the risk function
      for a large group of mice exposed to very low levels of a known carcinogen.

PMID- 11315078
TI  - A mover-stayer model for longitudinal marker data.
AB  - Studies of chronic disease often focus on estimating prevalence and incidence in
      which the presence of active disease is based on dichotomizing a continuous
      marker variable measured with error. Examples include hypertension, asthma, and
      depression, where active disease is defined by setting a threshold on a
      continuous measure of blood pressure, respiratory function, and mood,
      respectively. This paper proposes a model for inference about prevalence and
      incidence when active disease is determined by dichotomizing a continuous marker
      variable in a population-based study. In this formulation, it is postulated that
      there are three groups of people, those that are not susceptible to the disease,
      those who are always in the disease state, and those who have the potential to
      transition between the disease and the disease-free states over time. The model
      is used to estimate the prevalence and incidence of the disease in the population
      while accounting for measurement error in the marker. An EM algorithm is used for
      parameter estimation and the methodology is illustrated on Framingham heart study
      hypertension data. A simulation study is conducted in order to demonstrate the
      importance of accounting for measurement error in estimating prevalence and
      incidence for this example.

PMID- 11315079
TI  - Rank-based tests for dose finding in nonmonotonic dose-response settings.
AB  - Lim and Wolfe (1997, Biometrics 53, 410-418) proposed rank-based multiple test
      procedures for identifying the dose levels that are more effective than the zero
      dose control in randomized complete block designs when it can be assumed that the
      efficacy of the increasing dose levels is monotonically increasing up to a point,
      followed by a monotonic decrease. Modifications of the Lim-Wolfe tests are
      suggested that provide more practical and powerful alternatives. Two numerical
      examples are illustrated and the results of a Monte Carlo power study are
      presented.

PMID- 11315080
TI  - Estimating equations for removal data analysis.
AB  - We consider the problem of estimating a population size from successive catches
      taken during a removal experiment and propose two estimating functions
      approaches, the traditional quasi-likelihood (TQL) approach for dependent
      observations and the conditional quasi-likelihood (CQL) approach using the
      conditional mean and conditional variance of the catch given previous catches.
      Asymptotic covariance of the estimates and the relationship between the two
      methods are derived. Simulation results and application to the catch data from
      smallmouth bass show that the proposed estimating functions perform better than
      other existing methods, especially in the presence of overdispersion.

PMID- 11315081
TI  - The variance for the disequilibrium coefficient in the individual Hardy-Weinberg
      test.
AB  - It is of interest to detect the deviation from Hardy-Weinberg proportion (HWP)
      for a particular heterozygote. Hernandez and Weir (1989, Biometrics 45, 53-70)
      suggested a disequilibrium coefficient approach and proposed a 1-d.f. chi2 test.
      This note derives the appropriate variance under the null hypothesis for
      performing this individual HWP test. Examples of applying the test to human
      genetic disease data are presented.

PMID- 11315082
TI  - On the use of historical control data for trend test in carcinogenicity studies.
AB  - Historical control data are often available in carcinogenicity studies and are
      included for testing dose effects in current studies. A new method is developed
      for incorporating the historical control information into a dose effect test. The
      method generalizes the test procedures proposed by Tarone (1982, Biometrics 38,
      215-220) and Ibrahim and Ryan (1996, Biometrics 52, 1478-1485) by taking into
      account the variation resulting from parameter estimation based on historical
      data. Two examples are discussed for illustrating the proposed method.

PMID- 11315083
TI  - Multivariate elliptically contoured distributions for repeated measurements.
AB  - The multivariate power exponential distribution, a member of the multivariate
      elliptically contoured family, provides a useful generalization of the
      multivariate normal distribution for the modeling of repeated measurements. Both
      light and heavy tailed distributions are included. The covariance matrix retains
      its interpretation so that it can easily be structured for serial dependence and
      several levels of variance components. A crossover trial on insulin applied to
      rabbits, with a series of repeated measurements within each period, is analyzed
      by means of this distribution using autocorrelation and two levels of variance
      components.

PMID- 11315084
TI  - Polyhazard models for lifetime data.
AB  - We propose a polyhazard model to deal with lifetime data associated with latent
      competing risks. The causes of failure are assumed unobserved and affecting
      individuals independently. The general framework allows a broad class of hazard
      models that includes the most common hazard-based models. The model accommodates
      bathtub and multimodal hazards, keeping enough flexibility for common lifetime
      data that cannot be accommodated by usual hazard-based models. Maximum likelihood
      estimation is discussed, and parametric simulation is used for hypothesis
      testing.

PMID- 11315085
TI  - Adaptive sample size calculations in group sequential trials.
AB  - A method for group sequential trials that is based on the inverse normal method
      for combining the results of the separate stages is proposed. Without
      exaggerating the Type I error rate, this method enables data-driven sample size
      reassessments during the course of the study. It uses the stopping boundaries of
      the classical group sequential tests. Furthermore, exact test procedures may be
      derived for a wide range of applications. The procedure is compared with the
      classical designs in terms of power and expected sample size.

PMID- 11315086
TI  - Small-sample confidence regions in exponential families.
AB  - This article presents an algorithm for small-sample conditional confidence
      regions for two or more parameters for any discrete regression model in the
      generalized linear interactive model family. Regions are constructed by careful
      inversion of conditional hypothesis tests. This method presupposes the use of
      approximate or exact techniques for enumerating the sample space for some
      components of the vector of sufficient statistics conditional on other
      components. Such enumeration may be performed exactly or by exact or approximate
      Monte Carlo, including the algorithms of Kolassa and Tanner (1994, Journal of the
      American Statistical Association 89, 697-702; 1999, Biometrics 55, 246-251). This
      method also assumes that one can compute certain conditional probabilities for a
      fixed value of the parameter vector. Because of a property of exponential
      families, one can use this set of conditional probabilities to directly compute
      the conditional probabilities associated with any other value of the vector of
      the parameters of interest. This observation dramatically reduces the
      computational effort required to invert the hypothesis test to obtain the
      confidence region. To construct a region with confidence level 1 - alpha, the
      algorithm begins with a grid of values for the parameters of interest. For each
      parameter vector on the grid (corresponding to the current null hypothesis), one
      transforms the initial set of conditional probabilities using exponential tilting
      and then calculates the p value for this current null hypothesis. The confidence
      region is the set of parameter values for which the p value is at least alpha.

PMID- 11315087
TI  - Model choice and influential cases for survival studies.
AB  - Deletion diagnostics are developed for identifying observations that influence
      the estimates of regression parameters and the mixture parameter in the families
      of relative risk functions for failure time data. The diagnostic for the
      regression parameters is a generalization of Cain and Lange's (1984, Biometrics
      40, 493-499) measure of individual influence. The generalizations of martingale
      residuals, Schoenfeld's partial residuals (1982, Biometrika 69, 239-241), and
      score residuals by Therneau, Grambsch, and Fleming (1990, Biometrika 77, 147-160)
      are also obtained. The influence of some observations on regression parameters
      can be drastically modified as the mixture parameter changes, even for a very
      small change. In addition, adding or deleting some observations might result in
      choosing different models. The diagnostics are applied to a family proposed by
      Guerrero and Johnson (1982, Biometrika 69, 309-314). One illustrative example is
      presented.

PMID- 11315088
TI  - Multiple comparison of entropies with application to dinosaur biodiversity.
AB  - Did the biodiversity of dinosaurs decline, or did it remain more or less constant
      before their mass extinction 65 million years ago? Sheehan et al. (1991, Science,
      835-839) reported that the biodiversity of families of dinosaur species remained
      more or less constant preceding their extinction, suggesting extinction due to a
      cataclysmic event such as an asteroid strike. But that claim was based on the
      incorrect interpretation that a large p value associated with a test of null
      hypothesis of equality supports that null hypothesis. To assess whether there is
      a basis for such a claim, we formulate the problem as one of practical
      equivalence, in analalogy to bioequivalence. We then develop reliable practical
      equivalence confidence intervals for differences of entropies by applying the
      bootstrap-t technique to a nearly pivotal quantity. Confidence intervals for
      changes in the biodiversity of dinosaurs are then computed, allowing the reader
      to assess whether there is evidence of near constancy of dinosaur biodiversity
      before extinction.

PMID- 11315089
TI  - A hierarchical Bayesian model to predict the duration of immunity to Haemophilus
      influenzae type b.
AB  - A hierarchical Bayesian regression model is fitted to longitudinal data on
      Haemophilus influenzae type b (Hib) serum antibodies. To estimate the decline
      rate of the antibody concentration, the model accommodates the possibility of
      unobserved subclinical infections with Hib bacteria that cause increasing
      concentrations during the study period. The computations rely on Markov chain
      Monte Carlo simulation of the joint posterior distribution of the model
      parameters. The model is used to predict the duration of immunity to subclinical
      Hib infection and to a serious invasive Hib disease.

PMID- 11315090
TI  - A comment on optimal allocations for bioequivalence studies.
AB  - A method purporting to provide optimal allocations in bioequivalence studies
      fails to do so on both statistical and practical grounds. Reasons as to why this
      is so are given.

PMID- 11315091
TI  - Method for conducting sensitivity analysis.

PMID- 11315092
TI  - Genomic control for association studies.
AB  - A dense set of single nucleotide polymorphisms (SNP) covering the genome and an
      efficient method to assess SNP genotypes are expected to be available in the near
      future. An outstanding question is how to use these technologies efficiently to
      identify genes affecting liability to complex disorders. To achieve this goal, we
      propose a statistical method that has several optimal properties: It can be used
      with case control data and yet, like family-based designs, controls for
      population heterogeneity; it is insensitive to the usual violations of model
      assumptions, such as cases failing to be strictly independent; and, by using
      Bayesian outlier methods, it circumvents the need for Bonferroni correction for
      multiple tests, leading to better performance in many settings while still
      constraining risk for false positives. The performance of our genomic control
      method is quite good for plausible effects of liability genes, which bodes well
      for future genetic analyses of complex disorders.

PMID- 11315093
TI  - Focal adhesion kinase (FAK) phosphorylation is not required for genistein-induced
      FAK-beta-1-integrin complex formation.
AB  - It has previously been shown that changes in the activity of focal adhesion
      kinase (FAK), and its binding to beta-1-integrin, accompany genistein-induced
      adhesion of prostate cells. Consumption of genistein world wide is associated
      with a lower incidence of metastatic prostate cancer. Early human clinical trials
      of genistein are under way to evaluate genistein's potential causal role in this
      regard. Though an important cell adhesion-associated signaling molecule, FAK's
      role in regulating prostate cell adhesion was not clear. Elucidation of this
      process would provide important information relating to both biology and
      potential clinical endpoints. It was hypothesized that FAK activation and complex
      formation are temporally related in prostate cells, and can thus be separated.
      Significant activation of FAK was demonstrated when cells adhered to fibronectin,
      as compared to poly-L-lysine, thus demonstrating that beta-1-integrin plays a
      significant role in activating FAK. Neither FAK activation, nor FAK-integrin
      complex formation, required beta-1-integrin ligand. However, disruption of the
      cellular cytoskeleton by cytochalasin D prevented FAK activation, but did not
      block genistein-induced complex formation. In the face of a disrupted
      cytoskeleton, signaling through FAK could not be restored through either integrin
      cross linking, or re-establishment of tensile forces via attachment to solid
      matrix. These studies demonstrate that FAK-beta-1-integrin complex formation does
      not require FAK activation, suggesting that it is an early event in prostate cell
      adhesion. An intact cytoskeleton is necessary for FAK activation. The functional
      importance of beta-1-integrin in prostate cells is demonstrated. Current findings
      support plans to test genistein in prostate cancer.

PMID- 11315094
TI  - Chronologically-specific metastatic targeting of human pancreatic tumors in
      orthotopic models.
AB  - Pancreatic cancer is a highly metastatic disease that responds poorly to
      currently-available treatment. In order to better visualize and understand the
      chronology and specificity of metastatic targeting of pancreatic cancer, two
      human pancreatic cancer cell lines, expressing green fluorescent protein (GFP),
      were studied in orthotopic models. MIA-PaCa2-GFP and BxPC-3-GFP tumor fragments
      were transplanted by surgical orthotopic implantation (SOI) to the nude mouse
      pancreas for fluorescence visualization of the chronology of pancreatic tumor
      growth and metastatic targeting. BxPC-3-GFP tumors developed rapidly in the
      pancreas and spread regionally to the spleen and retroperitoneum as early as six
      weeks. Distant metastases in BxPC-3-GFP were rare. In contrast, MIA-PaCa-2-GFP
      grew more slowly in the pancreas but rapidly metastasized to distant sites
      including liver and portal lymph nodes. Regional metastases in MIA-PaCa-2-GFP
      were rare. These studies demonstrate that pancreatic cancers have highly specific
      and individual 'seed-soil' interactions governing the chronology and sites of
      metastatic targeting.

PMID- 11315095
TI  - Characterization of the frequency distribution for human hematogenous metastases:
      evidence for clustering and a power variance function.
AB  - When groups of mice are injected with cells from a metastasizing tumor, a
      minority of individuals within a given group tends to sustain disproportionately
      larger numbers of metastases relative to the remaining group members. This
      clustering of metastases obeys a power function relationship, sigma2 = amub,
      between the variance sigma2 and the mean number of lung metastases per animal mu
      (a and b constant). To see whether such clustering occurs with human lung, brain,
      and liver metastases, a meta-analysis of clinical and pathological series was
      performed. Thirty-three published series were identified that provided data
      regarding the numbers of organ metastases sustained by 5582 people. The data were
      grouped according to the primary tumor, site of metastasis and method of
      detection of metastases. Clustering of metastases within individuals of each
      subgroup (similar to the murine systems) was demonstrated by variance to mean
      ratios greater than 1, and by a strong correlation to the variance to mean power
      function (a approximately 0.49, b approximately 2.24, r2 = 96%, p < 10(-6)). The
      cause of this clustering remains unclear, but it may in part relate to
      heterogeneities in regional blood flow. As a consequence of this clustering,
      limited metastases would be expected to occur more frequently than predicted from
      random chance-providing for some optimism in the management of limited
      metastasis. As well, the frequency distribution for metastases revealed certain
      scaling symmetries, likely reflective of the underlying mechanisms of metastasis,
      that could be of interest to both clinicians and experimentalists working with
      metastasis.

PMID- 11315096
TI  - Persistence of human vascular endothelium in experimental human prostate cancer
      bone tumors.
AB  - Using the SCID-human model, we recently found that human circulating prostate
      cancer cells formed tumors in human bone but not mouse bone (Nemeth et al. Cancer
      Res 1999; 59: 1987-93). It is possible that this tissue preference was mediated
      by interaction between human tumor cells and human endothelial cells within the
      implanted bone tissue. We sought to determine the relative amounts of human and
      mouse vasculature within human bone implants and resulting prostate cancer bone
      tumors in the SCID-human model. Paraffin sections of plain bone implants or PC3
      or LNCaP human bone tumors were double stained for factor VIII (all vessels) and
      human CD31 (human vessels) followed by fluorescent secondary reagents. At 4 weeks
      post implantation (when cancer cells are typically introduced), the vasculature
      within human bone fragments remained primarily human (84.5%), and this pattern
      persisted to at least 10 weeks (91.6% human). Injection of PC3 cells into the
      bone resulted in an increase in mouse-derived vessels, however the majority (58%)
      of the vessels remained human even after the formation of large bone tumors.
      LNCaP bone tumors were highly angiogenic, and there was a sharp decline in the
      proportion of vessels which were antigenically human (36.8%), suggesting
      recruitment of mouse endothelial cells during the angiogenic process.
      Nonetheless, the persistence of human vasculature suggests the SCID-human model
      can be used to study the interaction between bone-seeking tumor cells, such as
      prostate cancer, and human bone endothelium in vivo, and to test potential
      therapeutic strategies which may depend on the presence of human vessels.

PMID- 11315097
TI  - In vitro modulation of human lung cancer cell line invasiveness by antisense cDNA
      of tissue factor pathway inhibitor-2.
AB  - Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine protease
      inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G and plasma
      kallikrein but not urokinase (uPA) or tissue-type plasminogen activator and
      thrombin. Earlier studies from our and other laboratories have shown that the
      production of TFPI-2 is downregulated during the progression of various cancers.
      To investigate the role of TFPI-2 in the invasion and metastasis of lung tumors,
      the human lung cancer cell line A549, which produces high levels of TFPI-2, was
      stably transfected with a vector capable of expressing an antisense transcript
      complementary to the full-length TFPI-2 mRNA. Northern blot analysis was used to
      quantify the TFPI-2 mRNA transcript, and western blot analysis was used to
      measure TFPI-2 protein levels in parental cells and stably transfected (vector
      and antisense) clones. The levels of TFPI-2 mRNA and protein were significantly
      less in antisense clones than in the parental and vector controls. The invasive
      potential of the parental cells and stably transfected vector clones in vitro, as
      measured by the Matrigel invasion assay, was also markedly less than that of
      antisense clones. Further characterization of these clones showed that more cells
      migrated from antisense clones than from parental and vector clones. These data
      suggest that TFPI-2 is critical for the invasion and metastasis of lung cancer
      and that the downregulation of TFPI-2 production may be a feasible approach to
      increase invasiveness and metastasis.

PMID- 11315098
TI  - Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas
      by the extracellular signal-regulated kinase and jun amino-terminal kinase
      signaling cascades.
AB  - Our previous studies have shown that MMP-9 levels are significantly elevated
      during the progression of human gliomas. In the current study, we examined the
      role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9
      production and the invasive behavior of the human glioblastoma cell line SNB19,
      in which JNK/ERK1 is constitutively activated. SNB19 cells that were transfected
      with dominant-negative JNK, MEKK, and ERK1 expression vectors showed reduced MMP
      9 promoter activity. In addition, conditioned medium collected from SNB19 cells
      transfected with these expression vectors showed diminished MMP-9 activity in the
      presence of phorbol myristate acetate, as determined by gelatin zymography. The
      cotransfection of SNB19 cells with kinase-deficient c-raf also diminished MMP-9
      promoter activity. Further, in the presence of a specific inhibitor of MEKK
      (PD098059), the Matrigel invasion assay showed the invasiveness of dominant
      negative SNB19 cells transfected with dominant-negative JNK1 or ERK1 to be
      remarkably reduced. In conclusion, our studies showed for the first time that MMP
      9 production and the invasive behavior of SNB 19 cells are regulated by JNK- and
      ERK-dependent signaling modules and that interfering with either of the pathways
      reduces invasiveness.

PMID- 11315099
TI  - Expression of bone sialoprotein and osteopontin in breast cancer bone metastases.
AB  - Bone sialoprotein (BSP) and osteopontin (OPN) are prominent, mineral-associated
      proteins in the extracellular matrix of bone that have been implicated in the
      metastatic activity of cancer cells. The expression of BSP, which is normally
      restricted to mineralizing tissues, has been observed in cancers with a high
      propensity for forming bone metastases. To investigate the relationship between
      BSP expression and the formation of bone metastases we have conducted an initial
      study of the expression of BSP in 10 intraductal breast carcinoma bone metastases
      using immunostaining and in situ hybridization, and compared the expression with
      OPN. The metastases were characterized by the infiltration of tumour cells into
      bone with extensive bone resorption evident. Moderate to strong staining for BSP
      was observed in all (100%) carcinomas, which also expressed BSP mRNA as
      determined by in situ hybridization. Variable staining for BSP was also observed
      in the mineralized bone and expression of BSP mRNA could be observed in
      osteoblastic cells on the bone surface and in some osteocytes at sites of bone
      remodelling. Contrary to a previous report, BSP expression could be demonstrated
      by PCR in three breast cancer cell lines, MCF-7, T47-D and MDA-MB-231. Moreover,
      in sub-cutaneous tumours formed by MDA-MB-231 breast cancer cells injected into
      athymic mice, higher immunostaining for BSP was seen in large ulcerating tumours
      in which mineral deposits were formed. In contrast to BSP, staining for OPN in
      bone metastases was generally restricted to the interface between tumor cells and
      bone surface of the carcinomas. While OPN staining was also observed in the
      cytoplasm of osteoclasts, which showed strong hybridization to a digoxygenin
      labelled OPN cRNA probe, expression of OPN was not clearly detectable in the
      tumour cells. These studies provide the first demonstration of BSP expression by
      tumour cells in bone metastases and support the concept that BSP may have a role
      in targeting metastatic cells to bone. Expression of OPN in bone metastases
      appears to be related to increased bone resorptive activity by osteoclasts.

PMID- 11315100
TI  - An orthotopic model of murine osteosarcoma with clonally related variants
      differing in pulmonary metastatic potential.
AB  - To provide an investigative tool for the study of osteosarcoma (OSA) biology we
      have developed a syngeneic (balb/c) murine model of OSA, using cell lines derived
      from a spontaneously occurring murine OSA (Schmidt et al. Differentiation 1988;
      39: 151-60). This model is characterized by orthotopic primary tumor growth, a
      period of minimal residual disease, spontaneous pulmonary metastasis, and
      clonally related variants (K7M2 and K12) that differ in pulmonary metastatic
      potential. Primary tumor and pulmonary metastasis histology was consistent with
      OSA in human patients. Expression of bone sialoprotein, biglyan, decorrin, and
      osteopontin was suggestive of bone lineage cells. The development and use of a
      more aggressive OSA cell line (K7M2) resulted in spontaneous metastasis to the
      lungs in over 90% of mice, whereas metastases were seen in only 33% of mice when
      a less aggressive OSA cell line (K12; Schmidt et al. Differentiation 1988; 39:
      151-60) was used. Death from metastasis occurred at a median of 76 days using
      K7M2 whereas no median was achieved after 140 days using K12. Angiogenic
      potential, characterized by CD31 and factor VIII staining of primary tumors and
      pulmonary metastases, was greater in the K7M2 model compared to the K12 model. No
      significant differences in the in vitro or in vivo expression of angiogenesis
      associated genes (flt1, flt4, TIE1, TIE2, and VEGF) was found between K7M2 and
      K12. This well characterized and relevant model of OSA will be a valuable
      resource to improve our understanding of the biology and treatment of metastasis
      in OSA.

PMID- 11315101
TI  - Inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP
      DG): inositol transferase, suppresses invasion ability by reducing productions of
      matrix metalloproteinase-2 and -9 and cell motility in HSC-4 tongue carcinoma
      cell line.
AB  - Inostamycin is an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol
      (CDP-DG): inositol transferase. It significantly reduced epidermal growth factor
      (EGF)-induced in vitro invasion of the tongue carcinoma cell line, HSC-4, through
      reconstituted basement membrane Matrigel. Since phosphatidylinositol (PI) 4,5
      biphosphate is important for signal transduction through protein kinase C and
      actin reorganisation, we further examined the effect of inostamycin on production
      of two matrix metalloproteinases (MMPs), MMP-2 and -9, and on cell motility.
      Zymographic analysis showed that inostamycin suppressed pro-MMP-2 and pro-MMP-9
      levels at a dose-dependent fashion, while MMP-2 activity was not significantly
      affected. By reverse transcription-polymerase chain reaction, it was found that
      inostamycin diminished steady state levels of MMP-2 and -9 but not membrane type
      1-MMP mRNA expressions. Inostamycin partially blocked both EGF- and phorbol 12
      myristate 13-acetate-stimulated pro-MMP-9 production. A cytoplasmic calcium
      chelator (BAPTA-AM) dramatically elevated pro- MMP-9 and slightly elevated pro
      MMP-2 secretions. EGF-stimulated motility of HSC-4 cells was suppressed by
      inostamycin treatment along with reduction of actin cytoskeletal reorganisation,
      filopodia formation and cdc42 expression. These results suggested that
      inostamycin would be useful for an anti-invasive agent in tongue cancer.

PMID- 11315102
TI  - Metabolic activation of o-phenylphenol to a major cytotoxic metabolite,
      phenylhydroquinone: role of human CYP1A2 and rat CYP2C11/CYP2E1.
AB  - 1. The in vitro metabolic activation of o-phenylphenol has been evaluated as
      yielding a toxic metabolite, 2,5-dihydroxybiphenyl (phenylhydroquinone), by p
      hydroxylation in liver microsomes of rat and human. The involvement of rat
      CYP2C11, CYP2E1 and human CYP1A2 in the p-hydroxylation of o-phenylphenol is
      suggested. 2. 2,3- and phenylhydroquinone, which induced DNA single-strand
      scission in the presence of 1 microM CuCl2, were the most cytotoxic chemicals
      examined to cultured mammalian cell lines among o-phenylphenol, m-phenylphenol, p
      phenylphenol, 2,2'-, 4,4'-, 2,3- and phenylhydroquinone. 3. Rat and human liver
      microsomes catalysed the formation of phenylhydroquinone, but not 2,3
      dihydroxybiphenyl, using o-phenylphenol as a substrate. A higher rate of
      metabolic activation of o-phenylphenol was observed with livers of the male than
      the female rats by 5.6- and 2.6-fold respectively. 4. Inhibitory antibodies
      against the male-specific CYP2C11 inhibited hepatic o-phenylphenol p
      hydroxylation in the male F344 and Sprague-Dawley rat by > 70%. Liver microsomes
      from the isoniazid-treated rats produced 1.8- and 3-fold induction of o
      phenylphenol p-hydroxylation and chlorzoxazone 6-hydroxylation (a CYP2E1
      dependent activity) respectively. 5. Human CYP1A2, expressed by baculovirus
      mediated cDNA expression systems, exhibited a remarkably higher capacity for o
      phenylphenol p-hydroxylation at concentrations of 5 (> 5-fold), 50 (> 2-fold) and
      500 microM (> 2-fold) than CYP2A, CYP2B, CYP2Cs, CYP2D6, CYP2E1 and CYP3A4 on the
      basis of pmol P450. 6. Among various CYP inhibitors tested here, 7,8-benzoflavone
      and furafylline, typical human CYP1A2 inhibitors, inhibited the microsomal p
      hydroxylation of o-phenylphenol in human livers most potently by 70 and 50%
      respectively. 7. The results thus indicate the involvement of rat CYP2C11/CYP2E1
      and human CYP1A2 in the hepatic p-hydroxylation of o-phenylphenol.

PMID- 11315103
TI  - Characterization of cytochrome P450 enzymes involved in drug oxidations in mouse
      intestinal microsomes.
AB  - 1. Cytochrome P450 (P450, CYP) enzymes involved in drug oxidations in mouse
      intestines were characterized for their role in the first-pass metabolism of
      xenobiotics. 2. Preparation of mouse intestinal microsomes using a buffer
      containing glycerol and protease inhibitors including (p-amidinophenyl)
      methanesulphonyl fluoride, EDTA, soybean trypsin inhibitor, aprotinin, bestatin
      and leupeptine gave the highest testosterone 6beta-hydroxylase activity among
      several preparation buffers tested in this study. Testosterone 6beta-hydroxylase
      activity catalysed by mouse intestinal microsomes subjected to freezing and
      thawing was lower than that catalysed by unfrozen intestinal microsomes. 3. Low
      but significant catalytic activities of nifedipine oxidation, midazolam 1'- and 4
      hydroxylation, chlorzoxazone 6-hydroxylation, bufuralol 1'- and 6-hydroxylations
      and tolbutamide methylhydroxylation were observed in mouse intestinal microsomes.
      Testosterone 6beta-hydroxylation, chlorzoxazone 6-hydroxylation, and bufuralol 1'
      and 6-hydroxylations were inhibited by ketoconazole, diethyldithiocarbamate and
      quinine respectively. 4. Immunoblot analysis using anti-rat CYP3A antibodies
      demonstrated two immunoreactive bands showing similar migration in mouse
      intestinal and hepatic microsomes, although studies using anti-CYP1A, anti-CYP2C,
      anti-CYP2D and anti-CYP2E1 antibodies did not detect any band in mouse intestinal
      microsomes. 5. The results suggest that mouse intestinal microsomes should be
      prepared with glycerol and several protease inhibitors and that Cyp3a enzymes
      probably play an important role in drug oxidations catalysed by mouse intestine.

PMID- 11315104
TI  - Metabolism of 7-benzyloxy-4-trifluoromethyl-coumarin by human hepatic cytochrome
      P450 isoforms.
AB  - 1. The metabolism of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) to 7-hydroxy-4
      trifluoromethylcoumarin (HFC) was studied in human liver microsomal preparations
      and in cDNA-expressed human cytochrome P450 (CYP) isoforms. 2. Kinetic analysis
      of the NADPH-dependent metabolism of BFC to HFC in four preparations of pooled
      human liver microsomes revealed mean (+/- SEM) Km and Vmax of 8.3 +/- 1.3 microM
      and 454 +/- 98 pmol/min/mg protein respectively. 3. The metabolism of BFC to HFC
      was determined in a characterized bank of 24 individual human liver microsomal
      preparations employing BFC substrate concentrations of 20 and 50 microM (i.e.
      about two and six times Km respectively). With 20 microM BFC the highest
      correlations were observed between BFC metabolism and markers of CYP1A2 (r2 =
      0.784-0.797) and then with CYP3A (r2 = 0.434-0.547) isoforms, whereas with 50
      microM BFC the highest correlations were observed between BFC metabolism and
      markers of CYP3A (r2 = 0.679-0.837) and then with CYP1A2 (r2 = 0.421-0.427)
      isoforms. At both BFC substrate concentrations, lower correlations were observed
      between BFC metabolism and enzymatic markers for CYP2A6, CYP2B6, CYP2C9, CYP2C19,
      CYP2D6, CYP2E1 and CYP4A9/11. 4. Using human beta-lymphoblastoid cell microsomes
      containing cDNA-expressed CYP isoforms, 20 microM BFC was metabolized by CYP1A2
      and CYP3A4, with lower rates of metabolism being observed with CYP2C9 and
      CYP2C19. Kinetic studies with the CYP1A2 and CYP3A4 preparations demonstrated a
      lower Km with the CYP1A2 preparation, but a higher Vmax with the CYP3A4
      preparation. 5. The metabolism of 20 microM BFC in human liver microsomes was
      inhibited to 37-48% of control by 5-100 microM of the mechanism-based CYP1A2
      inhibitor furafylline and to 64-69% of control by 5-100 microM of the mechanism
      based CYP3A4 inhibitor troleandomycin. While some inhibition of BFC metabolism
      was observed in the presence of 100 and 200 microM diethyldithiocarbamate, the
      addition of 2-50 microM sulphaphenazole, 50-500 microm S-mephenytoin and 2-50
      microM quinidine had little effect. 6. The metabolism of 20 microM BFC to HFC in
      human liver microsomes was also inhibited by an antibody to CYP3A4, whereas
      antibodies to CYP2C8/9 and CYP2D6 had no effect. 7. In summary, by correlation
      analysis, use of cDNA-expressed CYP isoforms, chemical inhibition and inhibitory
      antibodies, BFC appears metabolized by a number of CYP isoforms in human liver.
      BFC metabolism appears to be primarily catalysed by CYP1A2 and CYP3A4, with
      possibly some contribution by CYP2C9, CYP2C19 and perhaps other CYP isoforms. 8.
      The results also demonstrate the importance of the selection of an appropriate
      substrate concentration when conducting reaction phenotyping studies with human
      hepatic CYP isoforms.

PMID- 11315105
TI  - Use of everted sacs of mouse small intestine as enzyme sources for the study of
      drug oxidation activities in vitro.
AB  - 1. The use of everted sacs of the small intestine as an enzyme source for the
      study of the first-pass metabolism of xenobiotics by cytochrome P450s (P450, CYP)
      is described. Several drug oxidation activities for testosterone, chlorzoxazone,
      tolbutamide, bufuralol and warfarin were observed when everted sacs (1-cm
      segment) from different parts of mouse small intestine were incubated with an
      NADPH-generating system and each substrate. 2. Most of the drug hydroxylase
      activities resided in the upper part of mouse small intestine and these
      activities were much higher than those of intestinal microsomes. Drug oxidation
      activities decreased along the distance from the upper part of the small
      intestine except for warfarin hydroxylation. 3. Testosterone 6beta-hydroxylation
      in the everted sacs exhibited the highest catalytic activities among the drug
      oxidations tested here. In the upper part of the small intestine, the
      testosterone 6beta-hydroxylase activities of everted sacs subjected once to
      freezing and thawing were substantially decreased compared with the untreated
      everted sacs. 4. Testosterone 6beta-hydroxylase activities in the everted sacs of
      the small intestine were significantly inhibited by ketoconazole. Immunoreactive
      proteins using anti-CYP3A antibodies were detected in the upper and middle parts
      of the small intestine. 5. The results demonstrated that the upper part of the
      mouse small intestine serves as the major site for intestinal P450 mediated first
      pass metabolism. Everted sacs of the small intestine are therefore useful for the
      study of drug metabolism as well as of transport and absorption.

PMID- 11315106
TI  - Pharmacokinetics and disposition of the novel dopamine agonist Z-7760 in rat
      after intravenous and oral administration.
AB  - 1. Z-7760 (S(-)-N-[N-2-phenylethyl)-6-hexylamino]-N-propyl-5,6-dihydroxy-1,2,3,4
      tetrahydro-2-naphthylamine dihydrobromide) is a potent dopamine D-1 and D-2
      agonist synthesized during a search for agents to treat heart failure. Reported
      is the fate of the drug in rat. 2. 3H-Z-7760 was administered p.o. and i.v. to
      male Sprague-Dawley rats (0.4 mg and 400 microCi/kg in 0.1% ascorbic acid) and
      venous blood samples collected at intervals up to 48 h. Comparison of the AUC for
      total 3H showed that 37% of an oral dose of Z-7760 was absorbed. The percentage
      plasma 3H present as the parent compound fell from 82% 30 min after i.v. dosing
      to 12% after 24 h. After oral dosing, the fraction of plasma 3H present as
      unchanged Z-7760 was < 5% and this was essentially unaltered throughout the
      study. The long terminal elimination phase evident from 6 h was notable after
      both routes of administration. 3. The bile duct-cannulated rat was given 3H-Z
      7760 p.o. (0.4 mg and 40 microCi/kg) and bile was collected for up to 22 h.
      Biliary excretion accounted for 30% of the dose. No parent compound was detected
      in the bile. 4. In further studies, other rats were dosed p.o. or i.v. with 3H-Z
      7760 (0.4 mg and 400 microCi/kg) and urine and faeces were collected daily for 3
      days. The major route of excretion was the faeces with 94-97% 3H recovered after
      oral and 70-73% after i.v. dosing. A further 4-7% was recovered in the urine
      after oral and 12-13% after i.v. dosing. 5. After oral administration of Z-7760
      (100 mg/kg, 40 microCi/kg) to rats, the major metabolites in the urine were
      identified as the 5-O-methyl and glucuronic acid conjugates of Z-7760 by LC and
      MS. The glucuronide was only seen in urine after oral administration but 5-O
      methyl-Z-7760 was present in urine and faeces after both routes of
      administration. 6. The low bioavailability of Z-7760 is the consequence of its
      poor absorption from the gastrointestinal tract as well as extensive first-pass
      metabolism that further reduces systemic blood concentrations after oral
      administration.

PMID- 11315107
TI  - Determination, pharmacokinetics and protein binding of a novel tissue-type
      plasminogen activator, pamiteplase in human plasma.
AB  - 1. An enzyme-linked immunosorbent assay (ELISA) and functional bioassay to
      determine immunoreactive and bioactive concentrations of pamiteplase, a novel
      thrombolytic agent, in human plasma were developed. The ELISA and functional
      bioassay showed satisfactory accuracy and precision within a concentration range
      of 0.5-25 ng.ml(-1) and of 0.127-16.2 ng.ml(-1) respectively. 2. The
      pharmacokinetics of pamiteplase in healthy human subjects were evaluated using
      the ELISA and functional bioassay. Irrespective of the method used, plasma
      concentrations declined bi-exponentially. Half-lives in the beta phase were 1.25
      and 0.78 h, and AUCs were 507.9 and 286.4 ng.h.ml(-1) respectively. Total
      clearances of pamiteplase decreased to 19 and 31% of those of the wild-type
      tissue-type plasminogen activator. 3. The protein binding of pamiteplase in human
      plasma was investigated by gel filtration chromatography. Pamiteplase formed
      three high molecular weight complexes with alpha2-macroglobulin, C1-esterase
      inhibitor and alpha2-plasmin inhibitor in human plasma. This complex formation
      was relatively slow, and was thought to be irreversible and covalently bounded.
      Furthermore, this protein binding in humans resulted in the termination of
      biological action.

PMID- 11315108
TI  - Purification, cloning, and DNA sequence analysis of a chitinase from an
      overproducing mutant of Streptomyces peucetius defective in daunorubicin
      biosynthesis.
AB  - Extracellular chitinases of Streptomyces peucetius and a chitinase overproducing
      mutant, SPVI, were purified to homogeneity by ion exchange and gel filtration
      chromatography. The purified enzyme has a molecular mass of 42 kDa on SDS-PAGE,
      and the N-terminal amino acid sequence of the protein from the wild type showed
      homology to catalytic domains (Domain IV) of several other Streptomyces
      chitinases such as S. lividans 66, S. coelicolor A3(2), S. plicatus, and S.
      thermoviolaceus OPC-520. Purified SPVI chitinase cross-reacted to anti-chitinase
      antibodies of wild-type S. peucetius chitinase. A genomic library of SPVI
      constructed in E. coli using lambda DASH II was probed with chiC of S. lividans
      66 to screen for the chitinase gene. A 2.7 kb fragment containing the chitinase
      gene was subcloned from a lambda DASH II clone, and sequenced. The deduced
      protein had a molecular mass of 68 kDa, and showed domain organization similar to
      that of S. lividans 66 chiC. The N-terminal amino acid sequence of the purified
      S. peucetius chitinase matched with the N-terminus of the catalytic domain,
      indicating the proteolytic processing of 68 kDa chitinase precursor protein to 42
      kDa mature chitinase containing the catalytic domain only. A putative chiR
      sequence of a two-component regulatory system was found upstream of the chiC
      sequence.

PMID- 11315109
TI  - Removal of indicator bacteria, human enteric viruses, Giardia cysts, and
      Cryptosporidium oocysts at a large wastewater primary treatment facility.
AB  - Pathogens and fecal indicator bacteria occurrence and removal were studied for a
      period of 6 months at the Montreal Urban Community wastewater treatment facility.
      With a capacity of about 7.6 million cubic metres per day (two billion U.S.
      gallons per day), it is the largest primary physico-chemical treatment plant in
      America. The plant discharges a nondisinfected effluent containing about 20 mg/L
      of suspended matter and 0.5 mg/L of total phosphorus on the basis of average
      annual concentrations. BDO5 (annual mean) is 75 mg/L before treatment and 32 mg/L
      after treatment. Samples were collected for a period of 6 months, and they
      demonstrated that the plant was not efficient at removing indicator bacteria and
      the pathogens tested. Fecal coliforms were the most numerous of the indicator
      bacteria and their removal averaged 25%. Fecal streptococci removal was 29%,
      while Escherichia coli removal was 12%. In untreated sewage, fecal coliforms, E.
      coli, and human enteric viruses were more numerous in summer and early autumn.
      Fecal streptococci counts remained relatively similar throughout the period.
      Clostridium perfringens removal averaged 51%. Giardia cysts levels were not
      markedly different throughout the study period, and 76% of the cysts were removed
      by treatment. Cryptosporidium oocyst counts were erratic, probably due to the
      methods, and removal was 27%. Human enteric viruses were detected in all samples
      of raw and treated wastewater with no removal observed (0%). Overall, the plant
      did not perform well for the removal of fecal indicator bacteria, human enteric
      viruses, or parasite cysts. Supplementary treatment and disinfection were
      recommended to protect public health. Various alternatives are being evaluated.

PMID- 11315110
TI  - Effects of low temperature, cold shock, and various carbon sources on esterase
      and lipase activities and exopolysaccharide production by a psychrotrophic
      Acinetobacter sp.
AB  - The activities of isocitrate lyase, esterase, and lipase by the psychrotrophic
      Acinetobacter sp. strain HH1-1 were monitored during incubation at 25 degreesC, 5
      degreesC, and after a 25 degreesC to 5 degreesC down shift in growth temperature.
      During growth at 25 degreesC, isocitrate lyase activity was detected in cell-free
      extracts, but at 5 degreesC and after cold shock, activity was measured primarily
      in the cell culture supernatant. Strain HH1-1 produced two cell-associated
      esterases and an extracellular esterase and lipase. Activities of the
      extracellular esterase and lipase were reduced when cells were grown at 5
      degreesC and after cold shock. In contrast, an increased synthesis of a 53-kDa
      cell-associated esterase was observed 50 h after cold shock. An extracellular
      polysaccharide was also produced, indicated by a decrease in surface tension in
      cell culture supernatant when cells were incubated at 25 degreesC; but like
      extracellular enzyme activity, production of the exopolymer was reduced when
      cells were subjected to low temperatures. These results indicated that the
      intracellular enzyme, isocitrate lyase, leaked out of the cell after cold shock
      and during growth at 5 degreesC. The increased activity of a cell-associated
      esterase suggested this enzyme is required for growth at low temperatures. In
      contrast, activities of extracellular lipolytic enzymes and production of an
      extracellular polysaccharide were negatively affected at the lower temperatures.

PMID- 11315111
TI  - Regulation of nitrogenase in the photosynthetic bacterium Rhodobacter sphaeroides
      containing draTG and nifHDK genes from Rhodobacter capsulatus.
AB  - The photosynthetic bacteria Rhodobacter capsulatus and Rhodospirillum rubrum
      regulate their nitrogenase activity by the reversible ADP-ribosylation of
      nitrogenase Fe-protein in response to ammonium addition or darkness. This
      regulation is mediated by two enzymes, dinitrogenase reductase ADP-ribosyl
      transferase (DRAT) and dinitrogenase reductase activating glycohydrolase (DRAG).
      Recently, we demonstrated that another photosynthetic bacterium, Rhodobacter
      sphaeroides, appears to have no draTG genes, and no evidence of Fe-protein ADP
      ribosylation was found in this bacterium under a variety of growth and incubation
      conditions. Here we show that four different strains of Rba. sphaeroides are
      incapable of modifying Fe-protein, whereas four out of five Rba. capsulatus
      strains possess this ability. Introduction of Rba. capsulatus draTG and nifHDK
      (structural genes for nitrogenase proteins) into Rba. sphaeroides had no effect
      on in vivo nitrogenase activity and on nitrogenase switch-off by ammonium.
      However, transfer of draTG from Rba. capsulatus was sufficient to confer on Rba.
      sphaeroides the ability to reversibly modify the nitrogenase Fe-protein in
      response to either ammonium addition or darkness. These data suggest that Rba.
      sphaeroides, which lacks DRAT and DRAG, possesses all the elements necessary for
      the transduction of signals generated by ammonium or darkness to these proteins.

PMID- 11315112
TI  - Polyphasic taxonomy of the basidiomycetous yeast genus Rhodosporidium: R.
      azoricum sp. nov.
AB  - This report presents the description of a new heterothallic Rhodosporidium
      species, R. azoricum sp. nov. The new species is based on two strains previously
      identified as Rhodotorula glutinis, which were isolated from soil in Sao Miguel
      island, Azores, Portugal. Evidence that the two strains were conspecific and
      distinct from Rhodotorula glutinis was obtained in DNA fingerprinting experiments
      using the microsatellite-primed PCR approach (MSP-PCR) and the primers M13 and
      (GTG)5. In order to determine the phylogenetic position of the new species, the
      nucleotide sequence of the D1/D2 region of the 26S rDNA was analysed and
      Rhodosporidium azoricum was found to belong to a cluster including R. fluviale,
      R. lusitaniae, Sporidiobolus microsporus, and S. ruineniae. The life cycle of R.
      azoricum was investigated and comparisons integrating physiological,
      morphological, and molecular data were made with related species.

PMID- 11315113
TI  - Catalase activity and the survival of Pseudomonas putida, a root colonizer, upon
      treatment with peracetic acid.
AB  - Peracetic acid is used as a sterilant in several industrial settings. Cells of a
      plant-colonizing bacterium, Pseudomonas putida in liquid suspension, were more
      sensitive to killing by peracetic acid when they lacked a major catalase
      activity, catalase A. Low doses of peracetic acid induced promoter activity of
      the gene encoding catalase A and increased total catalase specific activity in
      cell extracts. Microbes present in native agricultural soils rapidly degraded the
      active oxygen species present in peracetic acid. The simultaneous release of
      oxygen was consistent with a role for catalase in degrading the hydrogen peroxide
      that is part of the peracetic acid-equilibrium mixture. Amendment of sterilized
      soils with wild-type P. putida restored the rate of degradation of peracetic acid
      to a higher level than was observed in the soils amended with the catalase A
      deficient mutant. The association of the bacteria with the plant roots resulted
      in protection of the wild-type as well as the catalase-deficient mutant from
      killing by peracetic acid. No differential recovery of the wild-type and catalase
      A mutant of P. putida was observed from roots after the growth matrix containing
      the plants was flushed with peracetic acid.

PMID- 11315114
TI  - Variability and interactions between endophytic bacteria and fungi isolated from
      leaf tissues of citrus rootstocks.
AB  - Fungi and bacteria were isolated from surface disinfected leaf tissues of several
      citrus rootstocks. The principal bacterial species isolated were Alcaligenes sp.,
      Bacillus spp. (including B. cereus, B. lentus, B. megaterium, B. pumilus, and B.
      subtilis), Burkholderia cepacia, Curtobacterium flaccumfaciens, Enterobacter
      cloacae, Methylobacterium extorquens, and Pantoea agglomerans, with P.
      agglomerans and B. pumilus being the most frequently isolated species. The most
      abundant fungal species were Colletotrichum gloeosporioides, Guignardia
      citricarpa, and Cladosporium sp. Genetic variability between 36 endophytic
      bacterial isolates was analysed by the random amplified polymorphic DNA (RAPD)
      technique, which indicated that B. pumilus isolates were more diverse than P.
      agglomerans isolates, although genetic diversity was not related to the host
      plants. In vitro interaction studies between G. citricarpa isolates and the most
      frequently isolated endophytic bacteria showed that metabolites secreted by G.
      citricarpa have an inhibitory growth effect on some Bacillus species, and a
      stimulatory growth effect on P. agglomerans.

PMID- 11315115
TI  - Intact soil-core microcosms compared with multi-site field releases for pre
      release testing of microbes in diverse soils and climates.
AB  - Intact soil-core microcosms were used to compare persistence of Pseudomonas
      chlororaphis 3732RN-L11 in fallow soil and on wheat roots with field releases at
      diverse sites. Parallel field and microcosm releases at four sites in 1996 were
      repeated with addition of one site in 1997. Microcosms were obtained fresh and
      maintained at 60% soil water holding capacity in a growth chamber at 70% relative
      humidity, a 12-hour photoperiod, and constant temperature. Persistence of 3732RN
      L11 was measured at each site in field plots and microcosms at 7-21 day
      intervals, and in duplicate microcosms sampled at an independent laboratory.
      Linear regression slopes of field plot and microcosm persistence were compared
      for each site, and between identical microcosms sampled at different sites, using
      log10 transformed plate counts. Microcosm persistence closely matched field plots
      for wheat roots, but persistence in fallow soil differed significantly in several
      instances where persistence in field plots was lower than in microcosms. Analysis
      of weather variations at each site indicated that rainfall events of 30-40 mm
      caused decreased persistence in fallow soil. Cooler temperatures enhanced
      persistence in field plots at later time points. Inter-laboratory comparison of
      regression slopes showed good agreement for data generated at different sites,
      though in two instances, longer sampling periods at one site caused significant
      differences between the sites. Soil characteristics were compared and it was
      found that fertility, namely the carbon to nitrogen ratio, and the presence of
      expanding clays, were related to persistence. These microcosm protocols produced
      reliable data at low cost, and were useable for pre-release risk analyses for
      microorganisms.

PMID- 11315116
TI  - Selective isolation and distribution of the genus Planomonospora in soils.
AB  - For the screening of bioactive compounds and study of global distribution, a
      selective isolation method for Planomonospora strains by centrifugation from soil
      is examined. Planomonospora strains produced characteristic sporangia on the
      humic acid-trace salts gellan gum medium (pH 9.0) so that this genus was readily
      recognized on the isolation plate. High yields of motile spores were obtained by
      using a flooding solution containing 0.1% skim milk in 5 mM N-cyclohexyl-2-amino
      ethanesulfonic acid (pH 9.0) followed by incubating the preparation at 32
      degreesC for 90 min, centrifuging it at 1000 x g for 10 min, and further
      incubation at 32 degreesC for 60 min after centrifugation. By combining the
      techniques described above, we isolated 246 Planomonospora strains from 137 of
      the 1200 soil samples examined. Ninety-four percent of these strains were
      recovered from neutral to slightly alkaline soils (pH 7.0 to 9.0). Strains of P.
      venezuelensis group were obtained from 13 soil samples (1.1%), which were
      collected in Bolivia, Cyprus, Egypt, Greece, India, Japan, New Caledonia, and
      Turkey. Strains of this group appear widely distributed in the soil of tropical
      to temperate regions. To our knowledge, this is the first record that strains of
      this group have been isolated from a location other than Venezuela.

PMID- 11315117
TI  - Possible involvement of Pseudomonas fluorescens and Bacillaceae in structural
      modifications of Tuber borchii fruit bodies.
AB  - Previous studies on Tuber borchii fruit bodies in early maturation stages
      suggested a role of bacteria in sporocarp structural modifications. In order to
      verify this hypothesis, in the present study we investigated by means of
      microbial and ultrastructural approaches, the bacterial population of T. borchii
      sporocarps from intermediate maturation phases to advanced decomposition stages,
      paying particular attention to chitinolytic and cellulolytic bacteria and to
      their relationships with ascii and ascospores. We found that Pseudomonas
      fluorescens and spore-forming Bacillaceae, both able to degrade cellulose and
      chitin, are present inside the sporocarps in all maturation stages investigated.
      Moreover, rod-shaped bacteria seem able to erode ascus walls and colonize the
      interior of ascii containing mature spores. These results suggest a possible role
      of these bacteria in the process of ascus opening. Moreover, the presence of P.
      fluorescens and Bacillaceae on isolated mature spores after decontamination
      suggests an intimate association between these bacteria and the ascospores.

PMID- 11315118
TI  - A common precursor for the three subunits of L-glutamate oxidase encoded by gox
      gene from Streptomyces platensis NTU3304.
AB  - A segment of DNA containing the L-glutamate oxidase (gox) gene from Streptomyces
      platensis NTU3304 was cloned. The entire nucleotide sequence of the protein
      coding portion consisting of 2130 bp (710 codons, including AUG and UGA) of the
      cloned DNA fragment was determined. The gox gene contained only one open reading
      frame (ORF) which coded for a 78-kDa polypeptide, the precursor of active
      extracellular Gox. Mature Gox is composed of three subunits, designated as alpha,
      beta, and gamma, with molecular masses of 39, 19, and 16 kDa, respectively.
      Analyses of the N-terminal amino acid sequences of the subunits revealed that the
      order of subunits in the precursor polypeptide encoded by the ORF, from N
      terminus to C-terminus, is alpha-gamma-beta. The presence of the flavin adenine
      dinucleotide (FAD)-binding motif place Gox as a member of the flavoenzyme family.
      Furthermore, a negative effect of glucose on the biosynthesis of Gox was observed
      when it was used as carbon source.

PMID- 11315119
TI  - Factor V Leiden and its relation to left ventricular thrombus in acute myocardial
      infarction.
AB  - OBJECTIVE: The genetic defect of coagulation factor V, known as factor V Leiden,
      produces a resistance to degradation by activated protein C (APC) and increases
      the risk of venous thrombosis. However, the role of factor V Leiden in the
      formation of left ventricular (LV) thrombus has not been studied. We investigated
      whether factor V Leiden is a risk factor for LV thrombus in patients with acute
      myocardial infarction (AMI). METHODS AND RESULTS: We have analyzed clinical,
      echocardiographic and biochemical data in 135 consecutive patients (aged 58 +/-
      13 years; 31 women) with first anterior AMI. Two-dimensional echocardiographic
      examination was performed on days 1, 3, 7, 15 and 30; LV thrombus was detected in
      33 (24.4%) of 135 patients with AMI. The study also included 95 control subjects.
      Healthy age and sex-matched subjects without a personal or family history of
      ischaemic heart disease, stroke or thromboembolic disease served as a control
      group. Blood samples from the patients and controls were analyzed for the factor
      V Leiden mutation by DNA analysis, using the polymerase chain reaction. In
      addition, concentrations of fibrinogen, von Willebrand factor (vWF), tissue
      plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D
      dimer were measured in 135 patients. There was no significant difference in the
      prevalence of factor V Leiden between patients and control subjects. The
      prevalence of the factor V mutation was 9% (3/33) in patients with thrombus, and
      7.7% (8/103) in patients without thrombus. The prevalence of factor V Leiden was
      7.3% (7/95) in control subjects. No significant differences in plasma fibrinogen
      (480 +/- 195 vs. 444 +/- 179 mg/dl, p = 0.6), D-dimer (471 +/- 256 vs. 497 +/-
      293 ng/dl, p = 0.7), vWF (112 +/- 18 vs. 103 +/- 15%, p=0.5), PAI-1 (26.7+/- 9.8
      vs. 28.1 +/- 10.2 ng/dl, p = 0.6), and t-PA (19.8 +/- 8.7 vs. 17.2 +/- 9.1 ng/dl,
      p = 0.7), levels are found in patients with LV thrombus when compared with those
      without LV thrombus. Multivariate analyses showed that peak creatine kinase level
      (p = 0.002) and LV wall motion score index (p = 0.003) were independent
      predictors of LV thrombus formation. CONCLUSION: Factor V Leiden mutation is not
      a risk factor for LV thrombus formation in patients with AMI.

PMID- 11315121
TI  - The association of silent electrocardiographic findings with coronary deaths
      among elderly men in three European countries. The FINE study.
AB  - OBJECTIVES: Ten-year coronary heart disease (CHD) mortality in elderly male
      cohorts in three European countries was evaluated as a function of silent resting
      Minnesota Code electrocardiographic (ECG) findings found at baseline. METHODS AND
      RESULTS: Men aged 65-84 at entry were enrolled, examined and followed up for 10
      years in 5 cohorts of three countries: Finland (N=716), the Netherlands (N= 887),
      and Italy (N = 682). Men with symptomatic angina pectoris, a documented history
      of myocardial infarction or heart failure were excluded from analysis, leaving
      505 men in Finland, 713 in the Netherlands and 567 in Italy. ECG abnormalities
      were arranged in different groupings. Multivariate analyses adjusted ECG
      prediction of CHD mortality for cohort, and baseline age, systolic blood
      pressure, serum cholesterol, body mass index and cigarette smoking. RESULTS:
      Silent ECG abnormalities of presumed severity were found in more than half of
      these elderly men, with higher prevalence in Finland, compared to the other two
      countries. Adjusted hazards ratios for CHD deaths as a function of major single
      or combined ECG abnormalities, such as QQS and ST-T abnormalities, arrhythmia,
      definite and possible myocardial infarction and an operative definition of
      ischaemia, are generally similar across areas varying according to severity from
      around 1.5 to almost 4. Groupings of minor and major ECG abnormalities in the
      pooled countries gave significant relative risks of 1.79 and 3.12 respectively,
      compared to the group without or with marginal abnormalities. Sensitivity and
      positive predictive value were low, while specificity was high. CONCLUSIONS:
      Silent ECG abnormalities in elderly people are common and they carry a high risk
      of coronary death in the next 10 years, with relative risk ranging from around
      1.5 to almost 4 or more depending upon severity and combination of findings.

PMID- 11315120
TI  - Treatment at discharge after myocardial infarction in 2,102 patients. The PRIMA
      study. Prise en charge de l'Infarctus du Myocarde Aigu.
AB  - OBJECTIVE: This study sought to examine the use of treatments at discharge in
      patients hospitalized for myocardial infarction in a French region. METHODS AND
      RESULTS: Data from 2,102 patients discharged after myocardial infarction were
      prospectively collected at 48 university, community, and private hospitals in
      three departments in the Rh ne-Alpes region between September 1, 1993 and January
      31, 1995. Beta-blockers were prescribed in 59% of the patients, calcium channel
      blockers in 22%, nitrates in 59%, antiplatelet agents in 82%, anticoagulants in
      26%, angiotensin-converting enzyme inhibitors in 36%, diuretics in 33%. Beta
      blockers were prescribed less often in older patients, and in patients with
      higher Killip classes or a history of pulmonary disease. Calcium channel blockers
      were prescribed more often in older patients, and in patients with a history of
      diabetes, pulmonary disease, or non-Q wave myocardial infarction. Nitrates were
      prescribed more often in older patients. Angiotensin-converting enzyme inhibitors
      were prescribed more often in patients with a history of diabetes, hypertension,
      or anterior myocardial infarction, and less often in patients with a history of
      renal failure. Diuretics were prescribed more often in older patients, and in
      patients with a history of renal failure, diabetes, hypertension, or higher
      Killip classes. CONCLUSIONS: There is still underuse of beneficial treatments,
      particularly in elderly patients.

PMID- 11315122
TI  - Aortic dissection presenting as fever of unknown origin.
AB  - Acute aortic dissection may have variable presentations, making the diagnosis
      clinically challenging. Although fever is a common accompanying feature, it
      rarely dominates the clinical setting. We report the case of a patient who
      sustained a prolonged spiking fever with unknown origin following acute aortic
      dissection. The case serves as a reminder that prolonged fever may be the
      principal residual sequelae after acute aortic dissection or one of the protean
      clinical manifestations of painless aortic dissection.

PMID- 11315123
TI  - Blurred vision, left bundle-branch block and cardiac failure.
AB  - We cared for a patient with progressive renal impairment who presented with
      blurred vision, QRS broadening and cardiac failure due to chronic cibenzoline
      intoxication. Treatment consisted of catecholamines and repetitive infusions of
      Ringer lactate. Cardiac function and symptoms recovered completely.

PMID- 11315124
TI  - Images in cardiology: left-sided inferior vena cava.

PMID- 11315125
TI  - High prevalence and suboptimal treatment of risk factors in Greek coronary
      patients.
AB  - OBJECTIVE: We assessed the current clinical practice in relation to secondary
      prevention of coronary heart disease in a general district hospital in Greece.
      METHODS AND RESULTS: A total of 819 consecutive patients ( < 75 years) with a
      history of myocardial infarction (> 6 months) was recruited from the outpatient
      cardiology clinic. All patients were interviewed and blood was taken for lipids
      and glycosylated haemoglobin measurements. Thirty-one percent of the patients
      were obese (body mass index > or = 30 kg/m2), 36% smoked cigarettes, 25% were
      diabetic and 36% were treated for hypertension. Reported prophylactic medication
      was aspirin 89%, beta-blockers 61%, angiotensin-converting enzyme inhibitors 33%
      and hypolipidaemic drugs 28%. Of those taking hypolipidaemic drugs 21% had
      achieved LDL cholesterol < 115 mg/dl while in total only 15% had LDL cholesterol
      < 115 mg/dl. Patients aware about the target cholesterol levels had lower
      cholesterol levels from those unaware (217 +/- 36 versus 231 +/- 46 mg/dl, p =
      0.0001). Only 50% of the coronary patients had desirable blood pressure levels
      (both systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm
      Hg) and half of the diabetic patients had an optimal glucose control
      (glycosylated haemoglobin < 7.5%). CONCLUSIONS: Our results show a high
      prevalence and suboptimal management of modifiable risk factors in Greek coronary
      patients. This should alert physicians and cardiologists to encourage their
      patients for effective lifestyle interventions together with more vigorous
      management of hyperlipidaemia, hypertension and diabetes and appropriate use of
      prophylactic drugs.

PMID- 11315126
TI  - Effects of L-arginine cardioplegia on myocardium.
AB  - Infusion of L-arginine (a precursor of nitric oxide, NO) in cardioplegia was
      examined to test its effect on metabolism of myocardium after myocardial ischemia
      and reperfusion (IR). Twenty-eight patients undergoing valve replacement were
      involved and randomly divided into two groups: the control group (crystalloid
      cardioplegia) and the experimental group (crystalloid cardioplegia + L-arginine).
      Blood samples were taken both before aortic clamping and after aortic unclamping
      from right radial artery to measure the concentrations of NO2-/NO3-, lactic acid
      (LA), malondialdehyde (MDA), superoxide dismutase (SOD), and xanthine oxidase
      (XOD). In the control group, the NO2-/NO3- level decreased at aortic unclamping,
      and 30 min later, it decreased significantly as compared with that before aortic
      clamping (p < .05). In the experimental group, it increased at aortic unclamping
      (p < .05), and 60 min later, increased to the peak. Five, fifteen, and thirty min
      after aortic unclamping, the concentrations of LA and MDA in the experimental
      group were lower than those in the control group (p < .05). Thirty and sixty min
      after aortic unclamping, the concentrations of SOD remained higher in the
      experimental group than those in the control group (p < .05). There was no
      difference between groups in the concentrations of XOD. The addition of L
      arginine to the cardioplegia can protect the myocardium from injury by releasing
      nitric oxide.

PMID- 11315127
TI  - In-vitro evaluation of the hemolytic effects of augmented venous drainage.
AB  - Augmentation of venous drainage with either kinetic-assisted drainage (KAVD) or
      vacuum-assisted (VAVD) has been used clinically in order to overcome added venous
      resistance due to smaller venous cannulae or tubing. This in-vitro study
      evaluates the extent of hemolysis and sub-lethal red blood cell membrane damage
      than occurs with augmented (kinetic or vacuum) when compared to conventional
      gravity drainage. Four trials were conducted using each test circuit. The
      circuits were primed with 6 liters of fresh heparinized bovine blood, which was
      diluted to a hematocrit of 32% and was recirculated at 5 L/min for 8 hours.
      Hemolysis was determined by the change in plasma free-hemoglobin (Hb),
      hematocrit, and potassium at two hour intervals. The red cell osmotic fragility
      index was used to quantify the sub-lethal red blood cell membrane damage and was
      also measured every two hours. After 8 hours, the mean +/- SD of the plasma free
      Hb were: 96.27 +/- 69.45 mg/dl for gravity, 83.87 +/- 48.14 mg/dl for vacuum
      assist, and 134.45 +/-83.78 mg/dl for kinetic-assist. Two-hour increases in the
      plasma free-Hb revealed the following median values (mg/dL/2 h): 16.90 for
      gravity, 13.75 for vacuum-assist, and 19.40 for kinetic-assist. Analysis of the
      two-hour increases in plasma free-Hb with Kruskal-Wallis One-Way ANOVA did not
      reveal a significant difference among the groups. After 8 hours, the red cell
      osmotic fragility test results at the 0.55% sodium chloride concentration were
      compared. The medians of the percent hemolysis were 52.67% for gravity, 49.8% for
      vacuum-assist, and 57.2% for kinetic-assist. Analysis with the Kruskal-Wallis
      Wallis One-Way ANOVA did not reveal a significant difference among the groups.
      Therefore, there is no significant increase in hemolysis or sub-lethal red blood
      cell membrane damage associated with the use of augmented venous drainage.

PMID- 11315128
TI  - A four-year experience with patient individualized heparin and protamine dosing
      using the Hemochron RxDx system.
AB  - Cardiac surgical case histories, collected over 4 years at Huntsville Hospital in
      Alabama, were reviewed for 2,293 patients. Patients were separated into two
      dosing groups for both heparin and protamine, hospital empirically dosed and
      Hemochron RxDx dosed. Review of the heparin dosing information found that
      incomplete data were collected for 47 patients, leaving 2,246 patients eligible
      to be evaluated for heparin dose comparison. Both RxDx recommended and
      empirically calculated doses were recorded, as well as the actual dose given. Of
      the 2,246 patients, 1671 were administered heparin according to the RxDx
      calculated dose, and the remaining 575 patients were dosed according to the
      hospital's empirical protocol. The average RxDx calculated heparin dose was 17%
      greater then the empirically calculated heparin dose (350 U/kg) (p < .001).
      Anticoagulation to target ACT (480 sec) was achieved in 92% of the patients dosed
      according to the RxDx recommended dose; whereas, in the empirically dosed patient
      group only 80% of the patients reached the target ACT after initial heparin bolus
      dose. Incomplete protamine dosing data was recorded for 336 patients, leaving a
      total of 1,957 patients available for protamine dose evaluation. All patients had
      an RxDx protamine calculation, empirical protamine calculation, and actual amount
      of protamine dosed recorded. Of the 1,953 patients, 1,764 were dosed according to
      the RxDx recommended dose, with the remaining 189 patients dosed empirically (1
      mg protamine/100 U of heparin). In both the RxDx and the empirical groups, 96% of
      the patients returned to baseline following initial protamine infusion. The
      overall RxDx dose (293 mg) was 16% lower than the average empirical dose (348
      mg). The RxDx system has been shown to be an effective method for determining
      patient-specific dosing for both heparin and protamine. This long-term clinical
      experience demonstrates the consistency and reliability of patient maintenance
      using this individualized dosing system, which has been shown, in other
      independent evaluations, to lead to improved patient outcomes.

PMID- 11315129
TI  - The influences of NO and Ach on cGMP levels in two patient populations.
AB  - Pulmonary hypertension following cardiac surgery is an important factor affecting
      postoperative mortality, and its mechanism has not been thoroughly clarified.
      Cardiopulmonary bypass (CPB) can destroy pulmonary endothelium and aggravate
      pulmonary hypertension. This study is designed to investigate the impacts of CPB
      on vascular endothelium-dependent relaxation, and the relations of CPB to
      pulmonary hypertension. Forty patients undergoing valve surgery were involved.
      According to their preoperative pulmonary arterial pressure (PAP), these patients
      were divided into pulmonary hypertension group (H group) and normal group (N
      group). The concentrations of cyclic guanosine monophosphate (cGMP) were measured
      at baseline conditions, after acetylcholine (Ach) injection, and during nitric
      oxide (NO) inhalation. Samples were taken before sternotomy and after weaning
      from CPB, 4 and 12 hours post-CPB. At baseline, the level of cGMP in the H group
      was lower than that of the N group by 33.9% before CPB. After initiating the CPB,
      although the level of cGMP continuously decreased in both groups until weaning
      from CPB (the N group decreased 33.3%, and the H group decreased 59%). At that
      point cGMP was higher in N group than in the H group (p < .01). The level of cGMP
      of both groups tended to recover 4 hours after CPB, but only the N group returned
      to baseline 12 hours after CPB. After injection of Ach, the level of cGMP of both
      groups followed the same change as in the baseline, except with different numeric
      value. The level of cGMP in N group rose ranging from 160.0-197.3%, while it rose
      ranging from 87.7-168.1% in H group. The levels of cGMP were higher in N group
      than those in H group at all times following injection of Ach (61.4, 173.3,
      202.7, and 188.0%) (p < .01). After inhalation of NO, the level of cGMP of both
      groups followed the same change as the baseline. The level of cGMP in N group
      rose ranging from 194.8-320.5%. Although the levels of cGMP were higher in N
      group than those in H group (6.9, 25.3, 23.3, and 16.6%), significant differences
      were achieved at the 4 and 12 hour post-CPB periods (p < .05 or p < .01,
      respectively). It was concluded that the injury of vascular endothelial function
      caused by CPB was more critical in pulmonary hypertension patients.

PMID- 11315130
TI  - An experimental evaluation of continuous cardiotomy reservoir ultrafiltration.
AB  - Ultrafiltration has been suggested as a means to reduce the morbidity associated
      with blood activation. However, the application of ultrafiltration to the highly
      activated blood of the cardiotomy suction subcircuit has not been investigated.
      The purpose of this study was to determine whether cardiotomy reservoir
      ultrafiltration (CRUF) would be effective in altering cytokine levels. Six swine,
      undergoing 90 min of cardiopulmonary bypass (CPB), were divided into two groups;
      one group was assigned to receive CRUF (N = 3), the other was to serve as
      controls and did not receive ultrafiltration (N = 3). Blood samples were analyzed
      for hematocrit, plasma-free hemoglobin, total protein, interleukin-8 (IL-8), and
      tumor necrosis factor alpha (TNF-alpha). Samples were taken pre-bypass,
      postheparinization, every 30 min during CPB, post-CPB and postprotamine. All data
      were analyzed using a one-way analysis of variance (ANOVA), with significance
      accepted at p < .05. There were no significant differences found between
      treatment and control groups for plasma-free hemoglobin levels (22.4 +/- 22.2 vs.
      14.6 +/- 14.4; 40.1 +/- 26.1 vs. 40.0 +/- 19.3). After 90 min of ultrafiltration,
      there was a significant decrease in TNF-alpha (261.6 +/- 119.6 vs. 71.8 +/- 11.4;
      p = .02). Although IL-8 levels decreased from throughout the experiment,
      concentrations did not reach statistical significance. In conclusion, CRUF can be
      used without increasing cellular destruction, and can decrease certain cytokine
      levels. Our results suggest that further clinical studies should be undertaken
      utilizing this technique with a larger sample size.

PMID- 11315131
TI  - Centrifugal pump and reduction of neurological risk in adult cardiac surgery.
AB  - This study was performed to assess if the kind of pump used for CPB (roller vs.
      centrifugal) can influence neurological outcomes of adult cardiac surgery
      patients. Between 1994 and 1998, 3438 patients underwent coronary and/or valve
      surgery at our hospital; of these, 1805 (52.5%) underwent surgery with the use of
      a centrifugal pump, and 1633 (47.5%) were operated with a roller pump. The effect
      of the type of the pump and of common preoperative and intraoperative risk
      factors for five different neurological outcomes (permanent neurological deficit,
      coma, delirium, transient neurological deficit, overall neurological
      complications) were assessed with univariate and multivariate analyses in the
      whole patients population, in patients > or = 75 years old and in patients with
      histories of previous neurological events. Centrifugal pump use was the only
      protective factor for perioperative permanent neurological deficit in
      multivariable models developed for the whole patient population and for patients
      > or = 75 years old. In addition, it resulted as the only protective factor for
      perioperative coma occurrence in multivariable models developed for patients > or
      = 75 years old, and for patients with histories of previous neurological events.
      The use of the centrifugal pump provided a risk reduction for the considered
      events ranging from 23 to 84%. Centrifugal pump use can be helpful in reducing
      the occurrence of some of the most feared neurological complications of adult
      cardiac surgery patients.

PMID- 11315132
TI  - Foot-and-mouth disease: two weeks and counting.

PMID- 11315133
TI  - FMD and horses: industry guidance for owners and event organisers.

PMID- 11315134
TI  - Foot-and-mouth disease in the United Kingdom, 2001.

PMID- 11315135
TI  - Pathology of natural Mycobacterium bovis infection in European badgers (Meles
      meles) and its relationship with bacterial excretion.
AB  - Sixteen European badgers (Meles meles) from three statutory removal operations
      were studied. Samples of tracheal aspirate, pooled lymph nodes and urine were
      cultured for mycobacteria. Seven of the badgers were infected with Mycobacterium
      bovis and had tuberculous pulmonary lesions which varied in severity from
      extensive granulomatous consolidation to microgranulomas which were not
      detectable grossly. Tuberculous lesions were also observed in the upper
      respiratory airways, intestines, kidneys, spleen, liver, thymus, pleura and lymph
      nodes. One badger had tuberculous bite wounds. The histopathological
      characteristics of the tuberculous reactions and the associated tissue damage in
      various organs, together with the gross pathology, indicate that both mildly and
      severely infected badgers have the potential to excrete M. bovis by several
      routes.

PMID- 11315136
TI  - Review of welfare concerns relating to commercial and special permit (scientific)
      whaling.
AB  - This paper reviews recent data relating to the efficiency and humaneness of the
      methods used to kill minke whales in commercial and special permit whaling
      operations. In the 1980s a grenade-headed harpoon was developed for minke
      whaling. Most recent results indicate that in the Norwegian industry
      approximately 60 per cent of whales were considered to be killed immediately by
      this harpoon, with 40 per cent being wounded. However, in Japanese whaling
      operations, generally only 30 per cent of whales were killed immediately, with 70
      per cent being wounded. In both operations, more than six minutes elapsed before
      half the wounded whales were pronounced dead, with some whales surviving for more
      than an hour after being harpooned. Many of the long killing times were
      associated with a failure of a part of the whaling equipment

PMID- 11315137
TI  - Asymmetric densitometric and mechanical adaptation of the left fifth metacarpal
      bone in racing greyhounds.
AB  - The densitometric and mechanical structural properties of the left and right
      fifth metacarpal bones of 10 racing greyhounds with a fracture of the central
      tarsal bone and 10 without a fracture were investigated by dual energy x-ray
      absorptiometry and a servo-hydraulic materials testing machine. In all the
      greyhounds the bone mineral density of the left fifth metacarpal bone was
      significantly greater than that of the right (P<0.001), but there was no
      significant difference between the degree of asymmetry in bone mineral density in
      the two groups. The ultimate torque and energy-to-failure of the left fifth
      metacarpal bone of the greyhounds with a fracture of the right central tarsal
      bone were significantly higher than in the right fifth metacarpal bone and higher
      than in both the left and right fifth metacarpal bones of the greyhounds with no
      fracture (P<0.05). The ultimate torque and energy-to-failure were significantly
      related to bone mineral density (P<0.005), and 22 per cent of the variation in
      these structural properties could be explained by variations in bone mineral
      density. Fifth metacarpal remodelling in response to asymmetric cyclic loading is
      bone-specific, and structural properties are enhanced in the left fifth
      metacarpal of greyhounds with a fracture of the right central tarsal bone.

PMID- 11315138
TI  - Postsampling stability of eye fluid magnesium concentrations in cattle.

PMID- 11315139
TI  - Behaviour of Indian river buffaloes (Bubalus bubalis) during short-haul road
      transportation.

PMID- 11315140
TI  - Ultrasonographic findings of urinary retention caused by a vaginal stricture
      following dystocia in a ewe.

PMID- 11315141
TI  - Foot-and-mouth disease outbreak.

PMID- 11315142
TI  - Foot-and-mouth disease outbreak.

PMID- 11315143
TI  - Foot-and-mouth disease outbreak.

PMID- 11315144
TI  - Foot-and-mouth disease in man.

PMID- 11315145
TI  - VN training scheme.

PMID- 11315146
TI  - Monitoring for Salmonella species in broilers.

PMID- 11315147
TI  - Communication skills training.

PMID- 11315148
TI  - Chronic bronchitis in dogs.

PMID- 11315149
TI  - Testing for CAE virus.

PMID- 11315150
TI  - Monitoring the purity of a synthetic peptide by capillary electrophoresis:
      utilization of an on-line preconcentration method for improved separation and
      detection sensitivity.
AB  - To date, there has been a considerable amount of interest and success in the
      pharmaceutical industry in the discovery of drug targets and diagnostics
      utilizing peptides. The success of peptide pharmaceuticals has, however, been
      accompanied by some failures, both prior to entry and in the clinic. Progress has
      been made in various areas to improve the effectiveness of the final drug
      product. One major advance has been in the area of peptide synthesis and control
      of the purity of the peptide of interest. Recent advances in analytical
      instrumentation, including advances in capillary electrophoresis, have had a
      great impact on the ability to separate and detect low quantities of impurities
      and degradation products during the synthesis of a peptide drug. In this work,
      affinity capillary electrophoresis (ACE) was developed for the identification and
      characterization of a chemically synthesized peptide fragment of a snake toxin
      called fasciculin. The affinity capillary electrophoresis technology utilized in
      this study employed two powerful techniques coupled on-line for the direct and
      rapid determination of analytes in simple and complex matrices. The first
      technique, aimed for the nonselective extraction and concentration of one or more
      analytes of interest, utilizes a solid-phase analyte concentrator device. The
      second technique, capillary electrophoresis, is used for the high-resolution
      analytical separation of the purified and concentrated target analyte(s), after
      elution from an analyte concentrator device. The on-line preconcentration step
      has proved valuable in terms of improving separation conditions as well as
      enhancing detection sensitivity values for the peptide fragment with a
      sensitivity increase ranging from 100- to 10,000-fold. Different types of analyte
      concentrator devices and a few binding-desorption conditions were tested. Bare
      and internal-wall-coated fused-silica capillaries were used. Comparative
      performance with HPLC in terms of selectivity and sensitivity is also discussed.

PMID- 11315151
TI  - Capillary electrophoresis of DNA for molecular diagnostics: an update.
AB  - The use of capillary electrophoresis in sieving liquid polymers for DNA analysis
      in the biomedical field is reviewed. One hundred and six references have been
      compiled and divided into the following categories: 1) screening for inherited
      human genetic defects, 2) quantitative gene dosage, 3) microbiology/virology, 4)
      forensic analysis, and 5) therapeutic DNA (antisense nucleotides).

PMID- 11315152
TI  - Method validation for diclofenac sodium in pharmaceuticals by capillary
      electrophoresis.
AB  - A capillary electrophoresis method for the determination of diclofenac sodium in
      a commercial and simulated tablet formation has been described. The aim of this
      research was to develop a rapid, simple, efficient, and economical method to
      determine diclofenac sodium in pharmaceutials. The analysis was carried out in a
      bare silica capillary (75 pm i.d.) with a total length of 50 cm (28 cm to the
      detector) with a buffer solution containing 20 mM sodium tetraborate, pH 9.23.
      The applied voltage was 20 kV. Detection was achieved by ultraviolet absorption
      at 276 nm. Acetaminophen was used as an internal standard. The calibration curve
      was linear to the concentration range from 40.0 to 120.0 microg/mL with a
      correlation coefficient of 0.9992. The percentage recovery was found to be 103.12
      +/- 0.91. The results showed that the method allows the determination of
      diclofenac sodium in commercially available pharmaceutical preparations.

PMID- 11315153
TI  - Comparisons of the separations of some neutral analytes by LC, MEKC, and CEC.
AB  - The relative utility of high-performance liquid chromatography, micellar
      electrokinetic chromatography (MEKC), and capillary electrochromatography (CEC)
      is examined for the separation of essentially uncharged solute mixtures. Three
      model systems are used for which separations by reversed-phase liquid
      chromatography had been established. These consisted of a set of three
      substituted hydroxybenzoates; a mixture of six structurally closely related
      steroids; and the multicomponent aminoglycoside antibiotic, teicoplanin. These
      sets represented a range of difficulty in achieving separations by reversed-phase
      LC. It was found that equivalent or better separations for all systems could be
      established by MEKC and CEC. Both electrophoretic techniques offer much higher
      peak efficiencies than LC, and MEKC is found to be superior to CEC in terms of
      peak efficiencies and ruggedness of operation.

PMID- 11315154
TI  - Dr. Karen C. Waldron.

PMID- 11315155
TI  - On-line solid-phase preconcentration for sensitivity enhancement in capillary
      electrophoresis.
AB  - Capillary electrophoresis is attractive for the analysis of biological samples
      because only a few nanoliters of sample need to be injected. Indeed, optimal
      resolution is achieved when the injected volume is 1% or less of the total
      capillary volume. Unfortunately, this advantage leads to severe detection
      limitations compounded by the fact that many analytes in a biological sample are
      present at very low concentrations. To overcome the detection sensitivity
      limitations of CE, nonspecific, on-line preconcentration has been employed in a
      variety of applications. This technique is based on inserting a small quantity of
      reversed-phase material (e.g., C18 particles or membrane) near the inlet of the
      CE capillary for sample enrichment by solid-phase extraction. A detachable
      cartridge containing the solid phase is relatively simple to construct and
      permits the injection of large sample volumes (1-100 microL) into the capillary.
      Elution of adsorbed analyte in less than 100 nL of solvent permits a 100-1000
      fold improvement in the effective concentration limit of detection, depending on
      the hydrophobicity of the compound. Detection of analytes present in complex
      mixtures at concentrations as low as 20 amol/microL has been reported when using
      an on-line preconcentration device in conjunction with CE-mass spectrometry. In
      this review, the potential merits of the technique are described and some
      examples of direct analysis of biological samples without rigorous off-line
      pretreatment are given.

PMID- 11315156
TI  - Determination of avoparcin in animal formulations by capillary electrophoresis.
AB  - The separation of two closely related glycopeptides, alpha- and beta-avoparcin,
      which differ by the presence or absence of a Cl atom, is achieved by capillary
      zone electrophoresis (CZE) using 20 mM borate (pH 9.2) in bare, fused-silica
      capillaries. The pKa values of these two glycopeptides are determined from
      spectrophotometric titrations of the mixture. Absorption spectra recorded between
      pH 3 and 12 produced a maximum pH transition at 258 nm. Titration data fitted to
      two sigmoidal functions reveal pKas of 7.99 for beta-avoparcin and 10.3 for alpha
      avoparcin. The differing pH dependence of the effective electrophoretic
      mobilities of alpha- and beta-avoparcin resulted in an optimum pH of 9.2 (roughly
      the average of the pKa values) for their separation. Borate is shown to be
      necessary for the optimal CZE separation. A linear dynamic range of 0.5-50 ppm is
      achieved with regression coefficients of 0.9999. The limit of detection ranges
      from 0.2 to 0.5 ppm using a pressure injection of 15 sec in a 50-cm (effective
      length) fused-silica capillary with UV detection. Finally, the effects of sodium
      dodecyl sulfate (SDS) concentration in the migration buffer on apparent mobility,
      efficiency, migration times, and resolution are discussed. The addition of 75 mM
      SDS to the running buffer allows baseline resolution of alpha- and beta
      avoparcin, including its minor components. Both the CZE and micellar
      electrokinetic chromatography (MEKC) separations of alpha- and beta-avoparcin are
      highly reproducible and can readily be applied to the analysis of avoparcin bulk
      drug and formulated products.

PMID- 11315157
TI  - A comparative study of fish species identification by gel isoelectrofocusing two
      dimensional gel electrophoresis, and capillary zone electrophoresis.
AB  - A comparative study of fish species identification was accomplished using three
      different electrophoretic techniques. Sarcoplasmic proteins were extracted from
      three related fish species and subjected to gel isoelectrofocusing (IEF), two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE), and capillary zone
      electrophoresis (CZE). The fish species--Genypterus chilensis, Genypterus
      blacodes, and Genypterus maculatus--were from the Ophidiidae family. The three
      electrophoretic techniques provided suitable fish species identification.
      Nevertheless, CZE demonstrated several advantages over the other two conventional
      techniques. Some of the benefits include the use of small amounts of reagents;
      short separation times, permitting fast comparative analysis; data
      reproducibility; and ease with which the technique is performed.

PMID- 11315158
TI  - Laser-based capillary polarimeter.
AB  - A laser-based capillary polarimeter has been configured to allow for the
      detection of optically active molecules in capillary tubes with a characteristic
      inner diameter of 250 microm and a 39-nL (10(-9)) sample volume. The simple
      optical configuration consists of a HeNe laser, polarizing optic, fused-silica
      capillary, and charge-coupled device (CCD) camera in communication with a laser
      beam analyzer. The capillary scale polarimeter is based on the interaction
      between a polarized laser beam and a capillary tube, which results in a 360
      degree fan of scattered light. This array of scattered light contains a set of
      interference fringe, which respond in a reproducible manner to changes in solute
      optical activity. The polarimetric utility of the instrument will be demonstrated
      by the analysis of two optically active solutes, R-mandelic acid and D-glucose,
      in addition to the nonoptically active control, glycerol. The polarimetric
      response of the system is quantifiable with detection limits facilitating 1.7 x
      10(-3) M or 68 x 10(-12) nmol (7 psi 10(-9) g) sensitivity.

PMID- 11315159
TI  - A review of capillary electrophoretic separations and their studies by nuclear
      magnetic resonance.
AB  - Capillary electrophoresis as a microvolume separation technique is receiving
      increased recognition for its use in the separation of inorganic and organic
      compounds due to its short analysis time and small sample volume in the nanoliter
      and picoliter ranges. The combination of capillary electrophoresis, one of the
      most-often employed chromatographic separation techniques, and studies by nuclear
      magnetic resonance (NMR) spectroscopy is finding an increased number of
      applications in pharmaceutical, biomedical, and polymer research. This paper
      discusses the applications of capillary electrophoresis for the separation of
      various analytes and their studies by NMR.

PMID- 11315160
TI  - The selection of marmoset monkeys (Callithrix jacchus) in pharmaceutical
      toxicology.
AB  - Prior to controlled clinical trials in human volunteers or patients it is
      required that novel pharmaceuticals are evaluated for pre-clinical safety in a
      rodent and a non-rodent ('second') species. In most cases the rodent species used
      has been the rat and the second species has been the dog or macaque (usually
      cynomolgus or rhesus) monkey. However, there is an increasing trend within the
      United Kingdom (UK) pharmaceutical industry to use the common marmoset
      (Callithrix jacchus) for pre-clinical toxicology programmes. This paper examines
      the practicality of using the common marmoset (henceforth referred to as 'the
      marmoset') in toxicological testing and reviews metabolic and pharmacodynamic
      similarities between this species and humans. It then discusses some of the
      advantages and disadvantages of the use of this species when compared with two
      other alternatives to the dog and macaque, namely the ferret and minipig. In
      particular, the marmoset has clear advantages over the macaque in terms of animal
      welfare and practicality. There is regulatory acceptance of this species for
      Investigational New Drug (IND), Clinical Trial Exemption (CTX), New Drug
      Application (NDA) and Marketing Authorization Application (MAA) registrations.
      Whilst the dog is likely to be maintained as the primary non-rodent species in
      toxicology, the marmoset has been, and will likely continue to be, adopted as an
      additional non-rodent species in pre-clinical toxicology programmes where
      appropriate.

PMID- 11315161
TI  - Blood sampling from the retro-orbital plexus, the saphenous vein and the tail
      vein in rats: comparative effects on selected behavioural and blood variables.
AB  - We compared the behaviours of rats, and measured various blood parameters, after
      three blood sampling techniques: orbital puncture while they were under diethyl
      ether anaesthesia, blood collection by tail vein puncture under O2-N2O-halothane
      anaesthesia and puncture of the saphenous vein without anaesthesia. Twelve rats
      were subjected to the three treatments according to a Latin square design. After
      each treatment, the behaviour of the rats was automatically monitored using the
      so-called LABORAS method, which discriminates between grooming, locomotion and
      inactivity in rats. Based on excitation scores and urine production, it was found
      that induction of diethyl-ether anaesthesia combined with orbital puncture caused
      more distress than did the other two blood sampling techniques. The three
      techniques had no differential effects on the behaviours of grooming, locomotion
      and inactivity. Collecting 0.5 ml of blood by orbital puncture was +/-7 times
      faster than doing so by saphenous vein puncture and +/- 15 times faster than
      collecting blood by tail vein puncture while the rats were under O2-N2O-halothane
      anaesthesia. The levels of some haematological and plasma variables differed
      significantly between the three blood collection techniques. These observations
      may help to select the most appropriate technique of blood sampling with respect
      to anticipated discomfort in the animals.

PMID- 11315162
TI  - Blood catalase and haematocrit values in a breeding colony of Dutch-belted
      rabbits.
AB  - Rabbit seminal plasma catalase is much higher than in the semen of other mammals,
      and differences appear to be inherited. Because of the scarcity of information on
      rabbit blood catalase and haematocrit in Dutch-belted rabbits, an investigation
      of possible effects of gender, age and genetics on these variables was
      undertaken. There were 191 rabbits sampled at 2-3 months, 130 at 12 months and 61
      at 18-24 months of age. There was no age effect on the haematocrit values and on
      blood catalase activity. At 12 months of age males had an average haematocrit
      value of 44% compared with 40% for females (P < 0.05). Corresponding average
      catalase values were 431 and 356 units/ml of blood (P < 0.05). Also catalase was
      measured in the semen and blood of 34 males, and males differed in both their
      blood and semen catalase activity (P < 0.05). The correlation between the two
      traits was r = 0.44. Heritability (h2) estimates, based on 231 rabbits were 0.40
      for blood catalase activity, and 0.26 for haematocrit. The genetic correlation
      between the two variables was 0.83 (P < 0.05). These studies are consistent with
      the literature in that female rabbits have a slightly lower haematocrit value
      than males, and this is associated with a lower catalase activity. This appears
      to be the first report of a study that compares rabbit blood catalase in males
      and females of different ages. Preliminary evidence that differences may have a
      heritable basis is consistent with previous studies on rabbit semen catalase.

PMID- 11315163
TI  - Effect of pre-analytical handling on haematological variables in minipigs.
AB  - Pre-analytical handling may be an important determinant of haematological
      variables, if analysis is delayed. We investigated the effect of anticoagulants,
      i.e. tripotassium ethylenediamine-tetraacetic acid (EDTA) and citric acid,
      theophylline, adenosine, dipyridamole (CTAD), storage time (0.5, 1.5, 3.5, 5.5,
      7.5, 25.5 and 27.5 h after blood sampling), and storage temperature (5 degrees C
      and 20 degrees C) on the variation in haemoglobin (HGB), red blood cell count
      (RBC), haematocrit (HCT), white blood cell count (WBC), and platelet count (PLT)
      in minipigs. Medians of HGB, RBC, HCT, WBC and PLT were significantly higher in
      EDTA tubes than in CTAD tubes due to the dilution effect of the anticoagulant. We
      found a minor significant increase in HCT after 25.5 h in blood stored at 20
      degrees C, and at the same time a minor significant increase in WBC in EDTA tubes
      stored at 20 degrees C. We found a significant decrease in PLT in blood stored at
      5 degrees C, especially in EDTA tubes. Minor variations were also observed in HGB
      and RBC. Our results indicate that PLT should only be measured in tubes placed at
      room temperature. If HCT or WBC analyses are to be performed on the day after
      blood sampling, the samples must be stored in a refrigerator until analysis. Our
      studies underline that time delay before analysis of haematological variables can
      cause increased variation, and should therefore be limited as far as possible in
      order to reduce the number of animals needed to make reliable conclusions.

PMID- 11315164
TI  - A simple polymerase chain reaction assay for genotyping the retinal degeneration
      mutation (Pdeb(rd1)) in FVB/N-derived transgenic mice.
AB  - FVB/N mice are one of the most common inbred strains for the generation of
      transgenic animals. This mouse strain is preferred for transgenesis because of
      its fertilized oocytes, which have unique pronuclei for microinjection, and its
      vigorous reproductive performance along with consistently large litter sizes.
      However, these inbred mice carry a retinal degeneration mutation caused by a
      proviral insertion into the Pdeb gene, encoding the beta subunit of cGMP
      phosphodiesterase. This mutation (Pdeb(rd1), formerly known as rd) results in
      postnatal rod photoreceptor degeneration and causes severe visual impairment,
      which may be relevant for behavioural and vision-related research. This deficit
      can be overcome by crossing these mice with other mouse strains carrying the wild
      type allele at the Pdeb locus. We have devised a simple polymerase chain reaction
      (PCR)-based method for distinguishing between the mutant and the wild-type
      alleles, thus allowing the efficient monitoring of the Pdeb(rd1) mutation in
      FVB/N-derived transgenic mice prior to experimentation where visual deficit is
      expected to have an influence in the phenotype.

PMID- 11315165
TI  - PCR-based microsatellite analysis for differentiation and genetic monitoring of
      nine inbred SENCAR mouse strains.
AB  - Sixteen DNA microsatellites or simple sequence length polymorphisms (SSLPs),
      generated by polymerase chain reaction (PCR) were selected for use in the genetic
      quality control of the nine inbred SENCAR strains currently available. The SENCAR
      strains constitute a powerful tool for mechanistic studies of multi-stage skin
      carcinogenesis, as well as for studies to understand the underlying genetic basis
      of resistance to tumour promotion and progression. SSLP analysis is a fast and
      economical way for detecting genetic contamination (unexpected outcrosses) among
      these closely-related albino strains, where standard immunological and
      biochemical markers have been shown to be insufficient.

PMID- 11315166
TI  - Survival and transmissibility of Pasteurella pneumotropica.
AB  - Survival has been determined for Pasteurella pneumotropica on various surfaces
      found in an animal room at 23+/-1 degrees C and 50+/-10% relative humidity.
      Longest survival (120 min) was found on mouse hair, shortest (< 30 min) on
      laboratory coat fabric. Transmission experiments were performed using sentinel
      animals in order to evaluate the efficiency of their use for the detection of P.
      pneumotropica in quarantined mice. In sentinels exposed to infected mice by close
      contact, P. pneumotropica was detected by culture 2 weeks post-exposure and
      seroconversion 3 weeks after contact. Transfer of soiled bedding from Pasteurella
      infected mice did not infect sentinels within a period of 12 weeks as tested by
      cultivation or serum antibodies.

PMID- 11315167
TI  - The use of diagnostic radiology to detect shell irregularities in the New Zealand
      paua (abalone) Haliotis iris.
AB  - A method is described for the non-destructive, non-invasive, detection of shell
      lesions in the New Zealand paua, a marine gastropod Haliotis iris using
      diagnostic radiology. The X-ray method reliably detected the presence of shell
      lesions in 96% of the cases examined once lesion dimensions exceeded 6.2 x 7.1
      mm. The extent of lesions above this size can be reliably and accurately
      determined from X-ray images viewed on a video display unit (VDU). Biofouling on
      the outside of the shell can cause misdiagnoses. This method is a significant
      animal welfare refinement in the identification of marine gastropods with shell
      lesions, when compared with traditional techniques which kill the animals.

PMID- 11315169
TI  - Insights from animal models for growing intestinal neomucosa with serosal
      patching--a still untapped technique for the treatment of short bowel syndrome.
AB  - The aim of surgical treatment of short bowel syndrome is to increase the
      intestinal absorptive capacity by increasing the area of absorption or by slowing
      intestinal transit. The use of serosal patching to grow new intestinal mucosa is
      a technique for enlarging the intestinal surface. The regenerated intestine
      develops by lateral ingrowth from the neighbouring mucosa and is functionally
      similar to normal intestinal mucosa. The present review summarizes the main
      contributions of the rabbit, the rat and the canine models used to date for
      growing neomucosa using the serosal patch technique, as well as examining the
      influence of some growth factors on the development of neomucosa.

PMID- 11315168
TI  - Induction of anaesthesia with desflurane and isoflurane in the rabbit.
AB  - The characteristics of two techniques of face-mask induction of desflurane
      anaesthesia (rapid or slow) were compared with the effects of slow isoflurane
      induction in five New Zealand White (NZW) rabbits. Slow induction used stepwise
      increments in vapour setting of 2% for desflurane and 0.5% for isoflurane at 30 s
      intervals. All animals were anaesthetized using each technique according to a
      randomized block design with one week between treatments. Observations were made
      of the quality of induction (any struggling or periods of apnoea) and the latency
      to, and the duration of loss of the righting and toe pinch reflexes recorded.
      Changes in respiratory rate, arterial blood gas and cardiovascular parameters
      were also recorded. Induction and recovery times were shorter with rapid
      desflurane induction in comparison to isoflurane (loss of righting reflex: 139+/
      27 s cf. 205+/-48 s), but both techniques were associated with struggling and
      long periods of apnoea (> 1 min) during the first 4 min after administration.
      During this period a significant degree of bradycardia, hypercapnia and
      hypoxaemia occurred with both techniques, but these and the subsequent effects of
      rapid desflurane administration were less severe than with isoflurane. Slow
      induction with desflurane was tolerated best, with little or no deleterious
      behavioural or physiological effects, however excessively prolonged induction
      times (loss of righting reflex 337+/-160 s) limits the application of this
      method. Desflurane, administered rapidly, appears to be a more suitable agent
      than isoflurane. However, as with isoflurane, anaesthesia should only be induced
      following oxygen supplementation.

PMID- 11315170
TI  - Undergraduate and postgraduate students' responses to mandatory courses (FELASA
      category C) in laboratory animal science.
AB  - The results from the analysis of the course evaluations from FELASA category C
      compulsory courses in laboratory animal science at Uppsala University showed that
      the students realize that theoretical knowledge of the subject and practical
      skills are of great importance to the success of their future research involving
      animal experiments. All the subjects and elements of the course, in particular
      the practicals on animal handling and procedures using live anaesthetized
      animals, were fully appreciated by the students.

PMID- 11315171
TI  - Plasmodium falciparum parasitaemia described by a new mathematical model.
AB  - A new mathematical model of Plasmodium falciparum asexual parasitaemia is
      formulated and fitted to 35 malaria therapy cases making a spontaneous recovery
      after primary inoculation. Observed and simulated case-histories are compared
      with respect to 9 descriptive statistics. The simulated courses of parasitaemia
      are more realistic than any previously published. The model uses a discrete time
      step of 2 days. Its realistic behaviour was achieved by the following combination
      of features (i) intra-clonal antigenic variation, (ii) large variations of the
      variants' baseline growth rate, depending on both variant and case, (iii) innate
      autoregulation of the asexual parasite density, variable among cases, (iv)
      acquired variant-specific immunity and (v) acquired variant-transcending
      immunity, variable among cases. Aspects of the model's internal behaviour,
      concerning variant dynamics, as well as the respective contributions of the three
      control mechanisms (iii) - (v), are displayed. Some implications for pathogenesis
      and control are discussed.

PMID- 11315172
TI  - Genetic typing and phylogeny of the Leishmania donovani complex by restriction
      analysis of PCR amplified gp63 intergenic regions.
AB  - Protozoan parasites of the Leishmania donovani complex (L. donovani, L.
      infantum/L. chagasi) are causative agents of visceral leishmaniasis. To
      understand phylogeny and taxonomy within this group better we have developed 2
      new polymerase chain reaction-linked restriction fragment length polymorphism
      (PCR-RFLP) analyses of the major surface protease (msp or gp63) intergenic (ITG)
      regions. We have named this approach msp intergenic region RFLP typing (MIRT).
      One intergenic region lies between the constitutive msp (mspC) and stationary
      phase msp (mspS4) genes (ITG/CS) and the other between multicopy logarithmic
      phase msp (mspL) genes (ITG/L). The markers generated robust and congruent
      phylogenies, identifying 5 genetic clusters within L. donovani. One cluster was
      synonymous with L. infantum (L. chagasi); clusters strongly correlated with
      isoenzyme typing and some with geographical origin. These genetic groups may be
      important for epidemiological and clinical studies. The congruence of the groups
      identified indicates suitability of these genomic targets for taxonomic studies.
      Furthermore, subgroups of L. donovani were of equivalent phylogenetic status to
      L. infantum. No evidence was found to support the existence of L. archibaldi. It
      is likely to be necessary in future to re-evaluate the taxonomic status of L.
      donovani or of L. infantum, as discrete species.

PMID- 11315173
TI  - Nuclear DNA sequence specific to Leishmania (Viannia) subgenus: a molecular
      marker for species identification.
AB  - As shown by RFLP analysis, there is a high variability in the beta-tubulin gene
      region of Leishmania sp. Such variability has been used in the identification of
      these parasites, establishing differences between subgenera of New World
      Leishmania. We have found a region of 500 bp (beta500) upstream of the coding
      region of the beta-tubulin gene that is present in all strains tested belonging
      to the L. (Viannia) subgenus. This region apparently is a repetitive sequence and
      we have shown that it is specific to the Leishmania (Viannia) subgenus. This
      sequence has no homology with the genomic DNA isolated from either the species
      belonging to the L. (Leishmania) subgenus or other Kinetoplastida, such as
      Trypanosoma cruzi, T. brucei, Leptomonas samueli, or Crithidia fasciciulata. The
      beta500 sequence showed sufficient variation to be used as a molecular marker in
      the identification of parasites. We established inter- and intrasubgenus
      differentiation and were able to discriminate at the species level in the Vianna
      subgenus. A PCR assay confirmed the specificity of the beta500 sequence.

PMID- 11315174
TI  - Schistosoma japonicum cathepsin D aspartic protease cleaves human IgG and other
      serum components.
AB  - Recombinant cathepsin D aspartic protease of Schistosoma japonicum cleaved human
      IgG in vitro in a time and dose-dependent manner. Optimal cleavage was seen at pH
      3.6-4.5; modest cleavage remained at pH 5.0, and no cleavage was detected above
      pH 5.0. Amino terminal sequencing of the major cleavage fragments of human IgG
      identified a Fab fragment from the VH1 domain, and 2 cleavage sites in the CH2
      domain below the hinge region. The P1 and P1' residues at the 2 CH2 cleavage
      sites were Phe254-Leu255 and Leu325-Thr326, indicating a preference by the
      schistosome protease for bulky hydrophobic residues flanking the scissile bond.
      No cleavage of the immunoglobulin light chain was detected. In addition, the
      recombinant schistosome protease indiscriminately degraded the human serum
      proteins complement C3 and serum albumin into numerous small fragments. These
      results demonstrate specific cleavage of human IgG by the recombinant schistosome
      aspartic protease, and highlight the broad range digestive specificity of the
      enzyme which may play a role in the degradation of host serum proteins ingested
      as part of the schistosome bloodmeal.

PMID- 11315175
TI  - Compatibility and sex in a snail-schistosome system.
AB  - Knowledge of the genetics underlying resistance to parasitic infection has
      important repercussions for our understanding of infection dynamics and the
      mechanisms of host-parasite co-evolution. The aim here was to determine for a
      Biomphalaria glabrato-Schistosoma mansoni system whether (1) resistance is
      dominant over susceptibility, (2) it is possible to crossbreed snails to be
      simultaneously resistant and/or susceptible to more than one parasite strain and
      (3) compatibility genotype affects reproductive strategy. Using replicate snail
      strains artificially selected for either resistance or susceptibility to single
      replicate parasite strains, individual snails from each line were paired with a
      selected partner of matched or non-matched compatibility status and cross
      breeding was identified by RAPD-PCR. The resulting compatibility phenotype of all
      offspring was determined. Support for all 3 hypotheses were obtained. The results
      are discussed in terms of their applied and theoretical implications.

PMID- 11315176
TI  - Integrin-like RGD-dependent cell adhesion mechanism is involved in the rapid
      killing of Onchocerca microfilariae during early infection of Simulium damnosum
      s.l.
AB  - Injection trials with compatible and non-compatible Onchocerca species into S.
      damnosum s.l., the vector of human and bovine onchocerciasis, demonstrated that
      the rapid killing of microfilariae within the blackfly's haemocoel is species
      specific. In the presence of the peptide RGDS as a blocking agent for integrin
      like receptors of haemocytes, the survival of O. ochengi microfilariae in its
      natural intermediate host was significantly increased. This increased survival 24
      h p.i. correlated with a significant decrease of apoptosis levels in the
      microfilariae following a 2 h exposure to the haemolymph in vivo. These findings
      suggest that haemocytes are directly involved in the killing of Onchocerca
      microfilariae in the blackfly.

PMID- 11315177
TI  - Intra-stadial tick-borne Thogoto virus (Orthomyxoviridae) transmission:
      accelerated arbovirus transmission triggered by host death.
AB  - Haematophagous insect vectors of arthropod-borne viruses (arboviruses) feed
      repeatedly. Consequently, they can transmit arboviruses to more than one host
      during the same developmental stage (intra-stadial transmission). By contrast,
      ixodid ticks generally feed only once at each parasitic stage (larva, nymph, and
      adult) and hence they have only one opportunity for tickborne virus transmission
      per stadium (inter-stadial transmission). Under natural conditions, tick-infested
      hosts may die (from disease or other causes) before the ticks have completed
      their long period of engorgement. A laboratory model was used to investigate the
      consequences of premature host death on tick-borne virus transmission. We report
      intra-stadial transmission of Thogoto virus by the nymphal, male, and female
      ticks of Rhipicephalus appendiculatus. Tick-borne Thogoto virus infection caused
      viraemia and death of hamsters before the nymphal and adult ticks feeding on them
      had completed engorgement. The resulting partially fed ticks were allowed to
      continue engorgement on new, uninfected hosts (interrupted feeding). During
      feeding on the subsequent hosts, they transmitted the virus intra-stadially to
      susceptible hosts (hamsters), and to uninfected co-feeding ticks on non
      susceptible hosts (guinea-pigs). Intra-stadial transmission, mediated by
      interrupted feeding, may help explain outbreaks of rapid and fatal tick-borne
      viral diseases, and the epidemiology as well as evolution of virulence, in a
      susceptible host population. Additionally, intra-stadial transmission provides an
      increased risk of tick-borne pathogen transmission to humans and domestic animals
      during slaughter and game hunting.

PMID- 11315178
TI  - Physiological effects of FMRFamide-related peptides and classical transmitters on
      dispersed muscle fibres of the turbellarian, Procerodes littoralis.
AB  - The physiological effects of selected classical transmitters and FMRFamide
      related peptides (FaRPs) on dispersed muscle fibres from the marine turbellarian,
      Procerodes littoralis have been examined. Confocal scanning laser microscopy
      coupled with fluorescein isothiocyanate (FITC) or tetramethylrhodamine (TRITC)
      labelled phalloidin revealed a highly developed body wall muscle system with
      circular, longitudinal and diagonal layers of muscle fibres. Dispersed muscle
      fibres contracted when depolarized by exposure to extracellular media with
      elevated K+ (15-100 mM) in a concentration-dependent manner, with a maximal
      response of 87% achieved at > or = 75 mM. 5-Hydroxytryptamine (5-HT) induced
      concentration-dependent muscle contraction between 0.01 and 1000 microM, with 10
      microM producing a near maximal contraction response of 75%. Acetylcholine (ACh)
      had less pronounced excitatory effects (0.01-1000 microM), inducing contraction
      of only 32% of the fibres at 100 microM. The flatworm FMRFamide-related peptides
      (FaRPs), GYIRFamide, YIRFamide and GNFFRFamide each had concentration-dependent
      myocontractile effects, indicating the occurrence of at least 1 FaRP receptor on
      P. littoralis muscle fibres. At 10 microM peptide, GNFFRFamide induced
      contractions in < 40% of the muscle fibres examined, whereas YIRFamide and
      GYIRFamide induced contraction in 70 and 75% of muscle fibres, respectively. The
      order of potency of the peptides was: GYIRFamide > YIRFamide > GNFFRFamide. Pre
      incubation of the muscle fibres in 5 microM 5-HT significantly reduced the
      responses to GYIRFamide, YIRFamide and 5-HT, while the responses to high K+
      remained unaltered. Muscle fibres pre-incubated in GYIRFamide (0.1 microM) were
      also less responsive to 5-HT but not to ACh and high-K+. The GYIRFamide analogue,
      GYIRDFamide, did not induce muscle contraction (0.01-100 microM) per se, but when
      co-applied with the myoactive peptides GYIRFamide, YIRFamide or GNFFRFamide, it
      significantly blocked their ability to elicit contractions. This suggests that
      the peptides tested may act via a common muscle-based neuropeptide receptor.
      GYIRDFamide did not alter the contractile effects of high K+, 5-HT or ACh.
      Collectively, these results indicate that FaRPs, 5-HT and ACh all have the
      potential to cause muscle contraction in flatworms and that 5-HT and FaRPs alter
      muscle sensitivity to each other, but do not influence the ability of flatworm
      muscle fibres to contract.

PMID- 11315179
TI  - No effect of a parasite on reproduction in stickleback males: a laboratory
      artefact?
AB  - Experiments are often carried out in the laboratory under artificial conditions.
      Although this can control for confounding factors, it may eliminate important
      factors that under natural conditions mediate the interaction under
      investigation. Here, we show that different results can be gained in the field
      and in the laboratory regarding host-parasite interaction. In the field, courting
      three-spined stickleback males, Gasterosteus aculeatus, were less often infected
      with plerocercoids of a cestode tapeworm, Schistocephalus solidus, than shoaling
      males. However, when a random sample of males was allowed to nest and court
      females in individual aquaria in the laboratory, both uninfected and infected
      males built nests and courted females. Moreover, while the few infected males
      that courted females in the field expressed less red nuptial coloration than
      uninfected courting males, there was no difference in redness between infected
      and uninfected males in the laboratory. We argue that the different results
      gained in the field and in the laboratory are due to differences in the cost of
      reproduction, due to differences in the resource pool of the males. The
      favourable conditions in the laboratory exclude factors such as predation risk,
      social interactions, and fluctuating environmental conditions that may use up
      resources in the field and mediate the effect of the parasite.

PMID- 11315180
TI  - Monogenean community structure on the gills of Pimelodus albicans from Rio de la
      Plata (Argentina): a comparative approach.
AB  - The community structure of monogeneans on the gills of a catfish Pimelodus
      albicans, in the Rio de la Plata, was studied and compared with previous findings
      on P. maulatus. Six Monogenea species belonging to 3 genera were found:
      Demidospermus majusculus Kritsky & Gutierrez, 1998; Demidospermus armostus
      Kritsky & Gutierrez, 1998; Demidospermus idolus Kritsky & Gutierrez, 1998;
      Demidospermus bidiverticulatum (Suriano & Incorvaia, 1995) Kritsky & Gutierrez,
      1998; Scleroductus yuncensi Jara & Cone, 1989; and Unibarra paranoplatensis
      Suriano & Incorvaia, 1995. The relationships between selected host and helminth
      variables; the interactions between the worms and the patterns obtained from the
      species abundance were analysed employing appropriate statistical methodology.
      The results obtained revealed the following common patterns within the monogenean
      communities of P. maculatus and P. albicans: (a) most monogenean species belonged
      to the genus Demidospermus; (b) S. yuncensi was a secondary species in both
      communities; (c) 1 of the 3 species common to both hosts was a core species (D.
      bidiverticulatum); (d) the selected variables of both hosts (weight and length)
      were not related to the number of monogeneans or species richness; (e) the
      dominant species in both communities showed the highest proportion of monogeneans
      in more than 40% of the infracommunities; (f) in both communities the dominant
      species accounted for 40-80% of the total number of monogeneans at component
      community level; (g) the number of worms correlates positively with the species
      richness; (h) few cases of interaction among species were found; (i) a high
      degree of order exists among the infracommunities compared. Finally, the
      proportion of common species and the phylogenetic and ecological resemblances
      between the hosts, P. maceulatus and P. albicans support a hypothesis of co
      speciation among monogeneans and pimelodids in Rio de la Plata. It seems
      improbable that these parasite communities are recent species assemblages formed
      by chance. The phylogenetic resemblance of the host-monogeneans system in Rio de
      la Plata suggests that there is a single community pattern that can be observed
      in congeneric and sympatric hosts.

PMID- 11315181
TI  - The structure of parasite component communities in brackish water fishes of the
      northeastern Baltic Sea.
AB  - We used nestedness analysis to seek non-random patterns in the structure of
      component communities of metazoan parasites collected from 31 sympatric fish
      species from the northeastern Bothnian Bay, the most oligohaline area of the
      Baltic Sea. Only 8 marine parasite species were found among the 63 species
      recorded, although some marine fish species reproduce in the bay and others
      occasionally visit the area. Marine parasite species can utilize both freshwater
      and marine fish species as intermediate or final hosts, and marine fish can
      harbour freshwater parasite species. This exchange of parasite species between
      marine and freshwater fish has probably resulted from ecological factors acting
      over short time scales rather than from evolutionary processes acting over longer
      time; the key factor probably being the immediate presence of suitable
      intermediate and definitive hosts. Marine fish were expected to harbour species
      poor parasite communities consisting mainly of generalists acquired from the
      sympatric freshwater fish species, which would result in a nested pattern among
      the different component communities. However, an anti-nested pattern was found in
      the component communities of metazoan parasites of fishes from the Bothnian Bay.
      A likely explanation for the observed pattern is that there are specialist
      parasite species, the majority of which are cestodes, in some of the freshwater
      fish species which otherwise have depauperate parasite communities.

PMID- 11315182
TI  - Costs of intraspecific and interspecific host sharing in acanthocephalan
      cystacanths.
AB  - Larval helminths often share individual intermediate hosts with other larval
      worms of the same or different species. In the case of immature acanthocephalans
      capable of altering the phenotype of their intermediate hosts, the benefits or
      costs of host sharing can be evaluated in terms of increased or decreased
      probability of transmission to a suitable definitive host. Competitive
      interactions among the immature stages of acanthocephalans within the
      intermediate host could create additional costs of host sharing, however. The
      effects of intraspecific and interspecific interactions were measured in 3
      sympatric species of acanthocephalans exploiting a population of the amphipod
      Echinogammarus stammeri in the River Brenta, Italy. The strength of interactions
      was assessed from differences in the size achieved by infective cystacanths in
      the intermediate host. The size of Pomphorhynchus laevis cystacanths was not
      correlated with host size, whereas the size of Acanthocephallus clavula and
      Polymorphus minutus cystacanths increased with host size. Reductions in
      cystacanth size caused by intraspecific competition were only detected in P.
      laevis, but may also occur in both A. clavula and P. minutus. When co-occurring
      in the same amphipod with cystacanths of A. clavula, cystacanths of P. laevis
      attained a smaller size than when they occurred on their own. This effect was not
      reciprocal, with the size of A. clavula cystacanths not being affected. This
      supports earlier suggestions that it is adaptive for A. clavula to associate with
      P. laevis in amphipod intermediate hosts, with both species going to the same
      fish definitive hosts. In contrast, cystacanths of P. laevis achieved their
      largest size when they co-occurred in an amphipod with a cystacanth of P.
      minutus, which has a different definitive host (i.e. birds). These findings
      suggest that the net benefits of sharing an intermediate host can only be
      estimated by taking into account both the effects on transmission success and the
      consequences for cystacanth development.

PMID- 11315183
TI  - To open or not to open that is the question: the replication of an entire
      chromosome.

PMID- 11315184
TI  - Some aspects of biochemistry of myocardial infarction.
AB  - This review deals with biochemical changes in infarcted heart muscle. Two main
      topics are emphasized: changes in substrate metabolism and in myocardial nitric
      oxide (NO), and prostacyclin and thromboxane formation. Alterations in glucose
      metabolism in infarcted heart are discussed with special reference to its
      myocardial utilization in ischemia. The biochemical basis of the increase in NO
      and prostanoids and the relationship between the enzyme producing nitric oxide
      (NOS) and cyclooxygenases (COX) responsible for formation of prostanoids are
      described. The relevance of these findings to clinical conditions and to
      angiogenesis in heart muscle are stressed.

PMID- 11315185
TI  - Apoptotic and necrotic cell death induced by death domain receptors.
AB  - Apoptosis and necrosis are two distinct forms of cell death. Caspases are
      indispensable as initiators and effectors of apoptotic cell death and are
      involved in many of the morphological and biochemical features of apoptosis.
      Major changes in mitochondrial membrane integrity and release of proapoptotic
      factors, such as cytochrome c from the mitochondrial intermembrane space, play an
      important sensor and amplifying role during apoptotic cell death. In vitro
      studies of cell death in cell lines have revealed that inhibition of the
      classical caspase-dependent apoptotic pathway leads in several cases to necrotic
      cell death. Thus, the same cell death stimulus can result either in apoptotic or
      necrotic cell death, depending on the availability of activated caspase.
      Therefore, death domain receptors may initiate an active caspase-independent
      necrotic signaling pathway. In this review, we describe what is known about the
      apoptotic and necrotic cell death pathways. Principal elements of necrosis
      include mitochondrial oxidative phosphorylation, reactive oxygen production, and
      non-caspase proteolytic cascades depending on serine proteases, calpains, or
      cathepsins.

PMID- 11315186
TI  - Cell-matrix contact structures.
AB  - Cell-extracellular matrix contacts are points on cell surfaces where adhesion
      receptors tether cells to matrix and are linked intracellularly to cytoskeletal
      components. These structures integrate cell organisation within tissues, support
      cell motility and specialised activities of differentiated cells, and transduce
      extracellular signals. Current characterisations of matrix contacts are based on
      morphological and biochemical criteria, yet the levels of definition of different
      contact types are very varied. Some contacts are surprisingly little-studied
      given their likely importance in vivo. Here, I describe the general features of
      matrix contacts, review the functions and molecular composition of major types of
      transient and stable matrix contacts, and discuss the information that is
      emerging on contact integration and dynamics in single cells.

PMID- 11315187
TI  - Genetic and molecular analysis of the synaptotagmin family.
AB  - Secretion is a fundamental cellular process used by all eukaryotes to insert
      proteins into the plasma membrane and transport signaling molecules and
      intravesicular proteins into the extracellular space. Secretion requires the
      fusion of two phospholipid bilayers within the cell, an energetically unfavorable
      process. A conserved repertoire of vesicle-trafficking proteins has evolved that
      function to overcome this energy barrier and temporally and spatially control
      membrane fusion within the cell. Within neurons, opening of synaptic calcium
      channels and subsequent calcium entry triggers synchronous synaptic vesicle
      exocytosis and neurotransmitter release into the synaptic cleft. After fusion,
      synaptic vesicles undergo endocytosis, are refilled with neurotransmitter, and
      return to the vesicle pool for further rounds of cycling. It is within this local
      synaptic trafficking pathway that the synaptotagmin family of calcium-binding
      synaptic vesicle proteins has been postulated to function. Here we review the
      current literature on the function of the synaptotagmin family and discuss the
      implications for synaptic transmission and membrane trafficking.

PMID- 11315188
TI  - Transposase and cointegrase: specialized transposition proteins of the bacterial
      insertion sequence IS21 and related elements.
AB  - The bacterial insertion sequence IS21 shares with many insertion sequences a two
      step, reactive junction transposition pathway, for which a model is presented in
      this review: a reactive junction with abutted inverted repeats is first formed
      and subsequently integrated into the target DNA. The reactive junction occurs in
      IS21-IS21 tandems and IS21 minicircles. In addition, IS21 shows a unique
      specialization of transposition functions. By alternative translation initiation,
      the transposase gene codes for two products: the transposase, capable of
      promoting both steps of the reactive junction pathway, and the cointegrase, which
      only promotes the integration of reactive junctions but with higher efficiency.
      This review also includes a survey of the IS21 family and speculates on the
      possibility that other members present a similar transpositional specialization.

PMID- 11315189
TI  - Molecular biology of chloroplast biogenesis: gene expression, protein import and
      intraorganellar sorting.
AB  - The chloroplast is the hallmark organelle of plants. It performs photosynthesis
      and is therefore required for photoautotrophic plant growth. The chloroplast is
      the most prominent member of a family of related organelles termed plastids which
      are ubiquitous in plant cells. Biogenesis of the chloroplast from
      undifferentiated proplastids is induced by light. The generally accepted
      endosymbiont hypothesis states that chloroplasts have arisen from an internalized
      cyanobacterial ancestor. Although chloroplasts have maintained remnants of the
      ancestral genome (plastome), the vast majority of the genes encoding chloroplast
      proteins have been transferred to the nucleus. This poses two major challenges to
      the plant cell during chloroplast biogenesis: First, light and developmental
      signals must be interpreted to coordinately express genetic information contained
      in two distinct compartments. This is to ensure supply and stoichiometry of
      abundant chloroplast components. Second, developing chloroplasts must efficiently
      import nuclear encoded and cytosolically synthesized proteins. A subset of
      proteins, including such encoded by the plastome, must further be sorted to the
      thylakoid compartments for assembly into the photosynthetic apparatus.

PMID- 11315190
TI  - Melanocortin receptors: their functions and regulation by physiological agonists
      and antagonists.
AB  - The melanocortins are a family of bioactive peptides derived from
      proopiomelanocortin, and share significant structural similarity. Those peptides
      are best known for their stimulatory effects on pigmentation and steroidogenesis.
      Melanocortins are synthesized in various sites in the central nervous system and
      in peripheral tissues, and participate in regulating multiple physiological
      functions. Research during the past decade has provided evidence that
      melanocortins elicit their diverse biological effects by binding to a distinct
      family of G protein-coupled receptors with seven transmembrane domains. To date,
      five melanocortin receptor genes have been cloned and characterized. Those
      receptors differ in their tissue distribution and in their ability to recognize
      the various melanocortins and the physiological antagonists, agouti signaling
      protein and agouti-related protein. These advances have opened new horizons for
      exploring the significance of melanocortins, their antagonists, and their
      receptors in a variety of important physiological functions.

PMID- 11315191
TI  - CD1d and natural T cells: how their properties jump-start the immune system.
AB  - Cellular and humoral immune mechanisms recruited to defend the host from
      infectious agents depend upon the early immune events triggered by antigen. The
      cytokine milieu within which the immune response matures is the most important of
      many factors that govern the nature of the immune response. Natural T cells,
      whose function is controlled by CD1d molecules, are an early source of cytokines
      that can bestow type 1 or type 2 differentiative potential upon helper T
      lymphocytes. This review attempts to illuminate the glycolipid antigen
      presentation properties of CD1d, how CD1d controls the function of natural T
      cells and how CD1d and natural T cells interact to jump start the immune system.
      CD1d is postulated to function as a sensor, sensing alterations in cellular lipid
      content by virtue of its affinity for such ligands. The presentation of a neo
      self glycolipid, presumably by infectious assault of antigen-presenting cells,
      activates natural T cells, which promptly release pro-inflammatory and anti
      inflammatory cytokines and jump-start the immune system.

PMID- 11315192
TI  - Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and
      white adipose tissue depots during rat development.
AB  - The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2
      and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue
      (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal,
      mesenteric and retroperitoneal) in male rats of different ages (18 days-12
      months). UCP mRNA expression levels were determined by Northern blotting. In BAT,
      there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable
      levels of UCP2 mRNA. Both ucp1 and ucp3 followed a similar expression pattern
      with age, with high levels in suckling rats which decreased to 50% or less in
      rats just under 2 months old, declining thereafter until 5 months and then
      recovering with age. However, an additional peak of expression was observed for
      ucp3 at the age of 3 months. In WAT, ucp1 expression was rare: occasional
      expression was found for UCP1 mRNA in the retroperitoneal depot in suckling rats
      and in the epididymal and inguinal depots in suckling and mature adult rats. ucp2
      and ucp3 had different developmental expression patterns, but these were similar
      for each gene in the different depots studied. UCP3 mRNA was highly expressed in
      rats soon after birth, it decreased until 3 months, and increased thereafter,
      except for the mesenteric WAT where ucp3 expression decreased until 7 months
      before recovering. The fact that changes with age of both ucp1 and ucp3
      expression have a similar profile in BAT, which is also similar to the ucp3 and
      also ucp1 profiles in some WAT depots, might reflect a common regulatory pattern
      for the expression of these genes, and also a common function. In contrast to
      ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower
      expression at 3 months, suggesting different regulation and probably a different
      role for this UCP.

PMID- 11315193
TI  - Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic
      function in perfused liver of young and old rats.
AB  - The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial
      respiration and biosynthetic function in perfused liver from young (90 days) and
      old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of
      acetyl-L-carnitine in their drinking water for 1 month and oxygen consumption
      together with the rate of gluconeogenesis, urea synthesis, and ketogenesis with
      and without added substrates were measured in perfused liver. Mitochondrial
      oxygen consumption was also assessed in liver homogenate and isolated
      mitochondria to determine the maximal capacity for oxidative phosphorylation.
      Acetyl-L-carnitine treatment almost completely restored the age-dependent decline
      in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in
      perfused liver of old rats to the levels found in young rats. In addition, acetyl
      L-carnitine treatment increased oxygen consumption and biosynthetic function in
      perfused liver from young rats. After acetyl-L-carnitine treatment, we found
      detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of
      ketone bodies in young and old rats. Finally, oxygen consumption measured in
      homogenate and isolated mitochondria did not change with age and acetyl-L
      carnitine treatment. Our results show that in perfused liver, acetyl-L-carnitine
      treatment slows the age-associated decline in mitochondrial respiration and
      biosynthetic function. In addition, treatment of young rats with acetyl-L
      carnitine has a stimulating effect on liver metabolism, probably through an
      increase in ATP production.

PMID- 11315194
TI  - Hydrogen peroxide and hydroxyl radical involvement in the activation of caspase-3
      in chemically induced apoptosis of HL-60 cells.
AB  - Apoptosis of HL-60 cells induced by actinomycin D, H7, or daunorubicin was shown
      to involve the activation of caspase-3-like protease, 2 h after the addition of
      these drugs, based on microassay of enzyme activity by high-performance liquid
      chromatography. Catalase and a spin trap, N-t-butyl-alpha-phenylnitrone, which
      effectively inhibited the apoptosis induced by these drugs, also inhibited the
      activation of caspase-3-like protease. These results suggest that hydrogen
      peroxide and the hydroxyl radical are common mediators of caspase-3 activation
      caused by these chemicals, with apparently different functional mechanisms. Based
      on mitochondrial activity determined by oxygen consumption, complexes I, II, and
      IV were inhibited by actinomycin D. H7 inhibited complexes I and IV, 1 and 1.5 h
      respectively, after the addition of the drug to HL-60 cells. Daunorubicin
      inhibited complex IV, 1.5 h after the addition of the drug to HL-60 cells.
      Inhibition of complex IV by actinomycin D, H7, and daunorubicin were almost fully
      restored by the addition of cytochrome c. The release to the cytosol of
      cytochrome c by these drugs was also demonstrated by Western blot analysis.
      Addition of catalase inhibited the depression of complex IV activity induced by
      actinomycin D and H7. These observations indicate a direct relationship between
      hydrogen peroxide and the release of cytochrome c during apoptosis caused by
      actinomycin D, H7, and daunorubicin.

PMID- 11315195
TI  - Distribution of tightened end fragments of globular proteins statistically
      matches that of topohydrophobic positions: towards an efficient punctuation of
      protein folding?
AB  - Using a set of 372 proteins representative of a variety of 56 distinct globular
      folds, a statistical correlation was observed between two recently revealed
      features of protein structures: tightened end fragments or 'closed loops', i.e.
      sequence fragments that are able in three-dimensional (3D) space to nearly close
      their ends (a current parameter of polymer physics), and 'topohydrophobic
      positions', i.e. positions always occupied in 3D space by strong hydrophobic
      amino acids for all members of a fold family. Indeed, in sequence space, the
      distribution of preferred lengths for tightened end fragments and that for
      topohydrophobic separation match. In addition to this statistically significant
      similarity, the extremities of these 'closed loops' may be preferentially
      occupied by topohydrophobic positions, as observed on a random sample of various
      folds. This observation may be of special interest for sequence comparison of
      distantly related proteins. It is also important for the ab initio prediction of
      protein folds, considering the remarkable topological properties of
      topohydrophobic positions and their paramount importance within folding nuclei.
      Consequently, topohydrophobic positions locking the 'closed loops' belong to the
      deep cores of protein domains and might have a key role in the folding process.

PMID- 11315196
TI  - Atypical "benign" partial epilepsy or pseudo-Lennox syndrome. Part I:
      symptomatology and long-term prognosis.
AB  - PURPOSE: Atypical benign partial epilepsy (ABPE) or pseudo-Lennox syndrome (PLS)
      is characterised by generalised minor seizures and focal sharp slow waves and
      spikes (SHW) as observed in Rolandic epilepsy (RE), but with exceptional
      pronounced activation during sleep. The aim of this study was to describe the
      full spectrum of ABPE in the hitherto largest group of patients. METHODS: We
      retrospectively analysed the clinical and EEG data of 43 children who fulfilled
      the following criteria: occurrence of generalised minor seizures as described for
      ABPE (i.e., atonicastatic seizures, myoclonic seizures, atypical absences) and
      focal SHW identical to those observed in RE, but with generalisation during
      sleep. RESULTS: Language development prior to onset of epilepsy was retarded in
      26% of patients. In 74%, age at onset of epilepsy ranged from 2 to 6 years.
      Manifestation occurred earlier in boys than in girls. Generalised minor seizures
      constituted the predominating seizure type in 67% of patients. Twenty-eight
      percent of patients suffered from simple partial seizures of the oro-facial
      region or generalised tonic-clonic seizures originating from the oro-facial
      region. Additionally, generalised tonic-clonic (44%), unilateral (21%), partial
      motor (44%), versive (12%), focal atonic (9%), and complex-partial seizures (2%)
      were observed. A bioelectrical status was recorded in 56% of patients during
      sleep. No tonic seizures and no fast spike series (bursts of 10-20 Hz rhythms)
      were observed. At last follow-up, 84% of patients were in clinical remission. All
      subjects older than age 15 were seizure-free. However, 56% of patients attended a
      school for mentally handicapped children. CONCLUSIONS: ABPE or PLS broadly
      overlaps with RE, electrical status epilepticus during sleep, and Landau-Kleffner
      syndrome. Regarding the epilepsy, the prognosis is excellent, mental deficit,
      however, seems to be frequent. The differentiation from Lennox-Gastaut syndrome
      and myoclonic astatic epilepsy is essential. Instead of ABPE, the term pseudo
      Lennox syndrome is proposed.

PMID- 11315197
TI  - Cobalamin (Cbl) C/D deficiency: clinical, neurophysiological and neuroradiologic
      findings in 14 cases.
AB  - The early onset type of cobalamin (Cbl) C/D deficiency is characterised by
      feeding difficulties, failure to thrive, hypotonia, seizures, microcephaly and
      developmental delay. It has an unfavourable outcome, often with early death and
      significant neurological impairment in survivors. While clinical and biochemical
      features of Cbl C/D deficiency are well known, only a few isolated case reports
      are available concerning neurophysiological and neuroimaging findings. We carried
      out clinical, biochemical, neurophysiological and neuroradiologic investigations
      in 14 cases with early-onset of the Cbl CID defect. Mental retardation was
      identified in most of the cases. A variable degree of supratentorial white matter
      atrophy was detected in 11 cases by MR imaging and tetraventricular hydrocephalus
      was present in the remaining 3 patients. Waking EEG showed a clear prevalence of
      epileptiform abnormalities, possibly related to the high incidence of seizures in
      these cases. Increased latency of evoked responses and/or prolongation of central
      conduction time were the most significant neurophysiological abnormalities. The
      selective white matter involvement, shown both by neuroradiologic and
      neurophysiological studies, seems to be the most consistent finding of Cbl C/D
      deficiency and may be related to a reduced supply of methyl groups, possibly
      caused by the dysfunction in the methyl-transfer pathway.

PMID- 11315198
TI  - Proton magnetic resonance spectroscopy (1H-MRS) of the cerebrum in two young
      infants with Zellweger syndrome.
AB  - Cerebral metabolic abnormalities have been previously detected by 1H-MRS in
      infants with the Zellweger syndrome as young as 3 months. We hypothesized that
      metabolic abnormalities could also be found shortly after birth. Two fullterm
      infants with Zellweger syndrome were studied at 12 days and two months of age,
      respectively, using single voxel 1H-MRS. In the first case 1H-MRS was performed
      using PRESS with variable TE (31, 136, 272 ms); in the second, STEAM and PRESS
      sequences were used with different TE (STEAM at 30 and 144 ms; PRESS at 270 ms).
      In both cases a significant decrease of N-acetylaspartate (NAA) and an abnormal
      signal at 1.33 and 0.9 ppm, consisting of lactate (Lac) and lipids (Lip) were
      found. The reported MRS abnormalities, although not specific for peroxisomal
      dysfunctions, may support the suspicion of Zellweger syndrome and may indicate
      direct referral to the specific laboratory and molecular studies necessary to
      establish the diagnosis and prognosis of this syndrome.

PMID- 11315199
TI  - Long-term MRI observations of childhood-onset relapsing-remitting multiple
      sclerosis.
AB  - PURPOSE: Long-term MRI follow-up of childhood-onset relapsing-remitting multiple
      sclerosis (RRMS) was carried out in 4 cases. MRI findings were correlated with
      clinical course and characteristic differences from adult-onset RRMS were
      elaborated. METHODS: Two girls and one boy with true childhood-onset, and one
      girl with juvenile-onset RRMS underwent 5-16 MRI examinations within 6-8 years.
      The total number of lesions, the numbers of new, active, disappearing and
      reappearing lesions, infratentorial and U-fibre lesions, "giant" plaques and
      "black holes" were counted. Callosal atrophy and general brain atrophy were
      assessed. The findings were related to the physical status according to the
      Expanded Disability Status Scale (EDSS). RESULTS AND CONCLUSIONS: Results showed
      that the primary differences in childhood-onset RRMS compared to adult-onset RRMS
      lie in the lack of, or slower development of irreversible changes ("black hole"
      formation, brain atrophy). Despite callosal atrophy and intensive U-fibre region
      involvement, school performance was unchanged. Regarding the frequency of "giant"
      lesions, an even more pronounced white matter involvement was found in our
      children compared to adults. All children exhibited a rather "benign" disease
      course. A more intensive remyelination, less severe neuronal loss, and higher
      functional brain plasticity at younger ages may account for these differences.

PMID- 11315200
TI  - Pitfalls in the diagnosis of multiple sulfatase deficiency.
AB  - Multiple sulfatase deficiency (MSD, OMIM 272200) is an autosomal recessive
      leukodystrophy associated with the deficiency of several, in total seven,
      sulfatases. The disorder is clinically and biochemically variable. The clinical
      picture combines features of mucopolysaccharidosis and metachromatic
      leukodystrophy (MLD, OMIM 250100) in a variable spectrum. Here we report a 3-year
      old Iranian girl with an MLD-like presentation of MSD. Arylsulfatase A deficiency
      and sulfatide excretion were found. Differently from what was previously reported
      in the literature, this girl never showed abnormal mucopolysaccharide excretion
      in the urine. There were no additional visceral or skeletal signs. She was
      originally diagnosed as having MLD. Only when she developed ichthyosis were seven
      additional sulfatases measured. In leukocytes, arylsulfatase A, steroid sulfatase
      and N-acetylglucosamine-6 sulfatase were profoundly deficient, while iduronate-2
      sulfatase and arylsulfatase B were moderately reduced. In fibroblasts, N
      acetylglucosamine-6 sulfatase was deficient, while arylsulfatase A was moderately
      reduced. This case illustrates the possible pitfalls in the clinical and
      laboratory diagnosis of MSD.

PMID- 11315201
TI  - Fulminant course in a case of diffuse myelinoclastic encephalitis-- a case
      report.
AB  - We report on a 10-year old previously healthy boy who exhibited a fulminant and
      nearly monophasic clinical course of demyelinating encephalitis with relapsing
      intracranial hypertension syndrome. Histologic examination of a diagnostic brain
      biopsy revealed an inflammatory demyelinating process with perivascular T
      lymphocytic infiltration and axonal damage reminiscent of multiple sclerosis-like
      lesions. In the brain, the DNA of human Herpes virus 6 (HHV6) was detectable.
      Eleven months after the initial symptoms and on maintainance with oral steroids,
      MRI showed demyelination of both hemispheres as well as demyelination of the
      brain stem and Wallerian degeneration. The boy exhibited a severe neurologic
      defect syndrome. The clinical and radiological course is unusual because of the
      asymmetric progression of the encephalitis and the extensive confluent lesions
      without demarcated border or enhancement of the rim after injection of
      gadolinium. The clinical course showed no definite steroid response. The
      pathogenetic relevance of HHV6 remains elusive. Although single patients with
      HHV6-associated encephalomyelitis have been reported, HHV6 DNA is occasionally
      detected in brains of healthy individuals.

PMID- 11315202
TI  - MRI and proton spectroscopy in Lowe syndrome.
AB  - The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder
      characterized by major abnormalities of eyes, nervous system, and kidneys. We
      report two patients with typical intracranial lesions on MRI. The proton
      spectroscopy study of the periventricular white matter showed a moderate
      elevation of the signal at 3.56 ppm in the patient with cystic lesions. This
      resonance is usually assigned to myo-inositol and interpreted as a glial marker.
      In our patient it could also represent a true accumulation inside the cysts of
      phosphatidylinositol 4,5-biphosphate which is not degraded in patients with Lowe
      syndrome.

PMID- 11315203
TI  - Arthrogryposis and multicystic encephalopathy after acute fetal distress in the
      end stage of gestation.
AB  - The natural history of the rare association "multicystic encephalopathy
      arthrogryposis" was traced in a fetus carefully followed after artificial
      insemination. The fetus exhibited normal viability and brain morphology up to the
      32nd week. At 36 weeks, active movements diminished and at 37 weeks, hydramnios
      and signs of fetal distress led to cesarean section. The infant presented with
      severe arthrogryposis of the limbs and spine, but not with the other elements of
      a long-lasting akinesia. US showed multicystic encephalopathy. Both the clinical
      and the neuropathological findings established that multicystic encephalopathy
      was neither the cause nor the sequential consequence of the fetal akinesia, but
      the result of a recent diffuse, acute malacic process that also involved the
      anterior horn cells. Acute fetal distress, responsible for major ischemic damage
      to CNS but compatible with fetal survival, remains an obscure condition which
      allows for the development of severe arthrogryposis in a few weeks.

PMID- 11315204
TI  - Atypical "benign" partial epilepsy of childhood or pseudo-lennox syndrome. Part
      II: family study.
AB  - Atypical benign partial epilepsy of childhood (ABPE = Pseudo-Lennox syndrome)
      shows semiologic parallels to Lennox-Gastaut syndrome, however--besides the lack
      of tonic seizures--it has an entirely different etiology and prognosis. Recently
      Hahn et al [17] investigated the long-term evolution of 43 cases with ABPE.
      Symptomatology, EEG findings, and course were found to overlap with Rolandic
      epilepsy, Landau-Kleffner syndrome and ESES. The incidence of seizures in
      relatives was determined in the whole series investigated by Hahn et al [17].
      Five of 56 siblings suffered from seizures (3 Rolandic seizures; one febrile
      convulsions; one unclassified). Three fathers reported grand mal. In 29 families
      of the series of Hahn et al EEG recordings were performed: 22 brothers, 19
      sisters and 16 pairs of parents. In 29% of the siblings a sharp wave focus was
      demonstrable. The rate rose to 40% when only siblings investigated at the age of
      maximum expression (3 to 10 years) were considered. Sharp wave foci were mostly
      multifocal and indistinguishable from those observed in siblings of children with
      Rolandic epilepsy. Photoparoxysmal response and generalized spikes and waves
      during rest and hyperventilation were also found to be significantly elevated
      (26% and 13% respectively). We conclude that ABPE is a subgroup of idiopathic
      partial epilepsy of childhood (representing a less benign part of a spectrum)
      that has to be ranked in a continuum with Rolandic epilepsy. The different
      clinical phenotype might be caused by a higher expressivity of the identical
      genetic trait, possibly facilitated by other genetic or acquired factors. Genetic
      heterogeneity represents another possibility.

PMID- 11315205
TI  - "Person first".

PMID- 11315206
TI  - Re: Psychiatric vocational rehabilitation: where are the customer's views?
      (Winter 2000, Psychiatric Rehabilitation Journal).

PMID- 11315207
TI  - A statewide assessment of psychosocial rehabilitation programs: general
      characteristics and services.
AB  - Psychosocial rehabilitation (PSR) encompasses a diverse array of skill-building
      and environmental support services for individuals with serious mental illness.
      The current study gleaned information from state Department of Mental Heath (DMH)
      databases and interviews with program directors to describe general
      characteristics and services of 22 out of 24 PSR programs in one New England
      state. Results underscored the relative predominance of services targeting social
      rehabilitation rather than vocational, educational, or residential
      rehabilitation. In addition, density of service provision across agencies was
      unrelated to enrollment or daily attendance statistics. Furthermore, low validity
      coefficients between mandated reporting statistics and information collected via
      interviews were found, suggesting the need to develop more valid and reliable
      reporting systems. Finally, four areas of concern were highlighted: substantial
      discrepancies between average membership enrollment and daily attendance, low
      percentages of peer-managed activities, predominance of services in traditional
      clinical settings, and lack of attention to multicultural issues.

PMID- 11315208
TI  - The experts speak: the critical ingredients of strengths model case management.
AB  - This study assessed the level of agreement among expert's opinion of the critical
      ingredients of the strengths model of case management. Twenty-eight experts rated
      the "significance" to the model of 72 elements/behaviors thought to be important
      and 8 distracter elements. There were also five open-ended questions asking for
      opinions on agency structure, service delivery, etc. The results found an
      extremely high agreement among the experts on virtually all items.

PMID- 11315209
TI  - Measuring the subjective well-being of people in a psychosocial rehabilitation
      center and a residential psychiatric setting: the outline of the study and the
      measurement properties of a multidimensional indicator of well-being.
AB  - The outline of an ongoing outcome research project in a day rehabilitation center
      and in a residential psychiatric setting (with respectively 156 and 86
      participants at baseline) in Bruges (Belgium) is presented. The study is first
      characterized by its emphasis on subjective well-being. Subjective well-being is
      considered to refer to more than satisfaction with specific domains of life, or
      the absence of psychiatric complaints. Attention is paid to feelings of
      empowerment, sense of control, feelings of joy and enthusiasm, and global self
      esteem. Various aspects of the social relations of the participants and their
      satisfaction with services are also assessed. Second, the investigation is based
      on a longitudinal design with intake interviews, retest interviews during and at
      the end of the rehabilitation programs, and a follow-up interview. Finally,
      specific efforts are made to ground the outcome measures in sociological theories
      of mental health to make a theory-driven evaluation possible. After presenting
      the rationale of the research project, some preliminary results are given, mainly
      confined to the determination of the reliability, the construct validity, and the
      sensitivity to change of the various indicators of well-being.

PMID- 11315210
TI  - Follow-up client satisfaction in a supported education program.
AB  - Satisfaction data have recently returned to popularity, as an outcome measure in
      managed behavioral healthcare systems. However, there are few examples of
      management uses of such data. We collected data 12 months after participants had
      completed a supported education program, concerning their retrospective
      satisfaction and the barriers, needs, and personal difficulties currently
      experienced in their attempts to pursue post-secondary education or training.
      Data on follow-up supportive contacts were also obtained. Results supported
      participants' continuing satisfaction, and identified particular information
      items which were endorsed as most helpful. However, the data indicated that
      personal difficulties presented obstacles to many and that a majority of
      participants had current needs for financial aid, tutoring, job placements,
      support groups, and transportation. Following completion of the supported
      education program, many participants had continuing contacts in support of their
      educational plans. The amount of contact was generally low, however. In the
      future, supported education programs need to build in mechanisms to ensure
      students receive ongoing support for education, since this support was found to
      positively and significantly affect individuals' enrolling in college or
      training.

PMID- 11315211
TI  - Experiencing recovery: a dimensional analysis of recovery narratives.
AB  - This paper applies the technique of dimensional analysis to recovery narratives
      in order to examine the uniqueness of the recovery process. It finds that there
      are four central dimensions involved in recovery: self, others, the system, and
      the problem. The recovery process is made up of component processes that
      correspond to these dimensions: recognizing the problem, transforming the self,
      reconciling the system, and reaching out to others. The paper concludes by
      suggesting how understanding these dimensions and processes may aid practice and
      policy.

PMID- 11315212
TI  - Empowerment effects of teaching leadership skills to adults with a severe mental
      illness and their families.
AB  - As consumers become proficient with advocacy skills, they are better able to
      impact the planning and provision of mental health and support services at the
      state and local levels. A Leadership Academy was conducted in Idaho to teach the
      basic skills necessary for adults with a mental illness and family members to
      become effective leaders in grassroots advocacy organizations. Participants
      learned to identify issues and develop and implement action plans to address
      those issues within the context of their local communities. While the first three
      sessions of the Academy were facilitated by professional instructors, the last
      two were led by consumers and family members who had graduated from the Academy.
      In the course of five sessions in three years, 160 consumers and family members
      graduated from the Leadership Academy. In a 27 months period, graduates took
      1,345 action steps to address issues of concern, with 400 outcomes, ranging from
      the establishment of a speakers bureau to starting a respite facility.

PMID- 11315213
TI  - Psychiatric rehabilitation principles for re-engineering board and care
      facilities.
AB  - Existing board and care facilities remain important for psychosocial
      rehabilitation because of scarcity of housing alternatives and advances in
      empowerment and skill transfer methods. Re-engineering board and care to mitigate
      the disadvantages of congregate housing requires a) a physical plant upgrade; b)
      home-like amenities; c) in-house programming; and d) collaboration with a
      psychiatric rehabilitation center. Continuing collaboration with the original
      owner of a commercial board and care home can be helpful, but requires careful
      coordination of the differing cultures. This article describes practical ways to
      convert an existing board and care facility.

PMID- 11315214
TI  - "It was just realizing ... that life isn't one big horror": a qualitative study
      of supported socialization.
AB  - This report describes the qualitative component of a large-scale study of
      supported socialization. Paralleling the recent advances made through supported
      housing, supported employment, and supported education, this approach seeks to
      increase the involvement of individuals with psychiatric disabilities in
      naturally occurring social and recreational activities in community settings of
      their choice. After a review of social relationships and psychiatric disability,
      we describe the Partnership Project and present findings from a series of
      qualitative interviews conducted with a subsample of participants. We then
      discuss the implications of these findings for the community integration of
      individuals with psychiatric disabilities.

PMID- 11315215
TI  - An evaluation of the social recreation component of a community mental health
      program.
AB  - The paper describes the results of an evaluation designed to determine the
      effectiveness of the social recreation component of a community-based mental
      health program. The program is for individuals with serious mental health
      problems, with a particular focus on those who perceive deficiencies in their
      social relationships. Findings showed that the individuals who participated in
      the program, in varying frequency, reported significant improvements in their
      self-ratings of loneliness, self-esteem, social functioning, satisfaction with
      social relations and leisure activities, as well as general life satisfaction.
      The association between particular program- or client-related factors and the
      outcome variables were examined to provide insights into why people changed. The
      merits and limitations of the evaluation methodology are discussed.

PMID- 11315216
TI  - Teaching in a new key: effects of a co-taught seminar on medical students'
      attitudes toward schizophrenia.
AB  - In order to examine the effect of a consumer and professional co-taught seminar
      on recovery in persons with schizophrenia, fourth year medical students completed
      attitudinal surveys at the beginning and end of their 7-week rotation in
      psychiatry. Analysis of results comparing average change in scores in a group
      exposed to the seminar (n = 24) and a control group not exposed (n = 10), shows
      measurable change in some survey items indicative of attitudinal change. Such a
      teaching format may provide a broader perspective on the long term issues for
      persons with schizophrenia. This can serve to counter the limitations of the
      brief exposure students receive to hospitalized patients in the most debilitating
      phase of the illness. The co-teaching model may provide a new and balanced
      perspective for medical students, facilitating a more holistic understanding of
      patients and countering a possible overemphasis on diagnosis. Such a format could
      have application in teaching psychiatric residents, nurses, and other health
      professionals.

PMID- 11315217
TI  - Out of the closet: escaping the stigma.

PMID- 11315218
TI  - Understanding the roles of genome and envirome: methods in genetic epidemiology.
AB  - BACKGROUND: In order to understand studies of psychiatric epidemiology focusing
      on the 'genome' and 'envirome', basic knowledge of the logic and methods is
      necessary. AIMS: To provide a review of typical methods used in genetic
      epidemiology. METHOD: Reviews of the research designs usually employed in
      quantitative and molecular genetic studies. Genotype-environment correlation and
      interaction are also discussed. RESULTS: Quantitative genetic studies indicate
      that genetic influences are important for both psychiatric disorders and
      behavioural traits. Specific gene loci can be tested for associations with both
      psychiatric risk and behavioural traits by means of molecular genetic techniques.
      There has been little examination of genotype-environment correlation and
      interaction, although the few reports that have appeared suggest that these
      complex relationships are important. CONCLUSIONS: Advances in quantitative and
      molecular genetics now permit more careful examination of genotype-environment
      interaction and correlation. Studies combining molecular genetic strategies with
      measurement of the environment are still at an early stage, however, and their
      results must be awaited.

PMID- 11315219
TI  - Genes, environment and schizophrenia.
AB  - BACKGROUND: Data from family, twin and adoption studies show overwhelming
      evidence of a substantial genetic component in schizophrenia and although
      molecular genetic studies have been more difficult to replicate, recent
      improvements in technology have resulted in the implication of genes at several
      chromosomal loci. Nevertheless, it remains clear that environmental factors both
      add to and interact with genetic factors to produce the disorder. AIMS: To
      incorporate genetic and environmental risk factors into a neurodevelopmental
      model in order to conceptualise the liability to schizophrenia. METHOD: A
      representative selection of the literature related to this issue is reviewed,
      together with a reformulation of Meehl's term 'schizotaxia' to describe the
      liability to the disorder. RESULTS: The literature supports a multi-factorial
      view of the liability to schizophrenia, which includes both genetic and
      environmental components. CONCLUSIONS: Schizotaxia provides a useful way to
      conceptualise both the liability for schizophrenia, and also the development of
      treatment strategies aimed at the eventual prevention of the illness.

PMID- 11315220
TI  - Obstetric complications and schizophrenia: prenatal underdevelopment and
      subsequent neurodevelopmental impairment.
AB  - BACKGROUND: Many studies have shown an association between obstetric
      complications and schizophrenia. AIMS: To investigate the possible relationship
      between prenatal underdevelopment, neurodevelopmental abnormality and subsequent
      schizophrenia. METHOD: The literature was reviewed. In particular, by pooling
      data from recently published reports, we examined whether low birthweight (< 2500
      g) is a risk factor for schizophrenia. RESULTS: Low birthweight was significantly
      more common for subjects with schizophrenia than for control subjects: P <
      0.00001, odds ratio 2.6 (95% CI 2.0 to 3.3). Individuals born prematurely are at
      greater risk of perinatal brain damage and subsequent neurodevelopmental
      abnormalities, which may constitute vulnerability to the development of
      schizophrenia. Patients with schizophrenia who had low birthweights also tended
      to have poor premorbid psychosocial adjustment. CONCLUSIONS: Low birthweight is a
      modest, but definite, risk factor for schizophrenia. Brain damage associated with
      prenatal underdevelopment has a role in the pathogenesis of poor premorbid
      functioning and subsequent neurodevelopmental impairment in some cases of
      schizophrenia.

PMID- 11315221
TI  - Moving on from old dichotomies: beyond nature-nurture towards a lifeline
      perspective.
AB  - BACKGROUND: Genetics is increasingly being used to explain human behaviours, with
      growing enthusiasm for what could be termed 'genetic determinism', which an ultra
      Darwinist approach seeks to apply to all aspects of the human condition. AIMS: To
      consider the validity of the claims concerning the genetics of human behaviour
      and psychological distress. METHOD: A critical review of the current assumptions
      about the relative contributions of genetics and the environment. RESULTS AND
      CONCLUSIONS: Organisms are in constant interaction with their environment: that
      is, organisms select environments just as environments select organisms. Like
      organisms, environments evolve and are homeodynamic rather than homeostatic; both
      'genome' and 'envirome' are abstractions from this continuous dialectic.

PMID- 11315222
TI  - Epidemiology in neurobiological research: exemplified by the influenza
      schizophrenia theory.
AB  - BACKGROUND: During recent years the strategy for aetiological research in
      schizophrenia has been to concentrate on two closely connected directions: the
      search for the genetic element and the search for environmental factors. Damage
      to the immature brain during pregnancy and delivery has given us the most
      interesting results from recent environmental research. AIMS: To examine the
      validity of the influenza-schizophrenia hypothesis. METHOD: A review of register
      based epidemiological studies in Denmark conducted over a 10-year period.
      RESULTS: The studies reviewed provided strong inferential evidence in favour of
      the hypothesis, but some methodological problems are unresolved and not all
      replication studies have been positive. CONCLUSIONS: The brain-damage hypothesis
      points to possibilities for identifying high-risk individuals at an early stage
      of life and perhaps establishing specific preventive programmes. There is,
      however, a great need for closer international collaboration in future research.

PMID- 11315223
TI  - Towards a molecular epidemiology of alcohol dependence: analysing the interplay
      of genetic and environmental risk factors.
AB  - BACKGROUND: Progress in identifying genetic factors protective against alcohol
      dependence (AlcD) requires a paradigm shift in psychiatric epidemiology. AIMS: To
      integrate analysis of research into the genetics of alcoholism. METHOD: Data from
      prospective questionnaire and interview surveys of the Australian twin panel, and
      from a subsample who underwent alcohol challenge, were analysed. RESULTS: In men,
      effects of alcohol dehydrogenase ADH2*1/*2 genotype or high alcohol sensitivity
      (risk-decreasing), and of history of childhood conduct disorder, or having
      monozygotic co-twin or twin sister with AlcD (risk-increasing) were significant
      and comparable in magnitude. Religious affiliation (Anglican versus other) was
      associated with the ADH2 genotype, but did not explain the associations with AlcD
      symptoms. No protective effect of the ADH2*1/*2 genotype was observed in women.
      CONCLUSIONS: The early onset and strong familial aggregation of AlcD, and
      opportunity for within-family tests of genetic association to avoid confounding
      effects, make epidemiological family studies of adolescents and young adults and
      their families a priority.

PMID- 11315224
TI  - Genetics, environment and cognitive abilities: review and work in progress
      towards a genome scan for quantitative trait locus associations using DNA
      pooling.
AB  - BACKGROUND: Multivariate genetic research indicates that genetic effects on
      diverse cognitive abilities are general rather than specific or modular. General
      cognitive ability (g), a key factor in learning and memory, is among the most
      heritable behavioural traits. AIMS: To give a brief overview of quantitative
      genetic research on g and to describe initial results from a programme of
      research that aims to identify genes responsible for the substantial heritability
      of general cognitive ability. METHOD: The research uses a new technique called
      DNA pooling, which combines DNA from individuals within a group and makes it
      feasible to screen thousands of DNA markers for a systematic scan of the genome
      for associations between DNA markers and g. Two independent samples of children
      with very high g scores and two control samples of children with average g scores
      were compared in a systematic scan of 147 markers on chromosome 4 and 66 markers
      on chromosome 22. RESULTS: Three replicated associations on chromosome 4 were
      identified using DNA pooling and confirmed using individual genotyping.
      CONCLUSIONS: These first results of the application of DNA pooling in systematic
      analysis of allelic association are encouraging.

PMID- 11315225
TI  - Effect of prenatal exposure to polychlorinated biphenyls on cognitive development
      in children: a longitudinal study in Taiwan.
AB  - BACKGROUND: From 1978 to 1979, a group of people in Taiwan were exposed to high
      levels of heat-degraded polychlorinated biphenyls (PCBs) owing to accidental
      ingestion of contaminated rice oil. Children born to mothers following the
      exposure ('Yucheng' children) were known to have hyperpigmented skin and other
      dysmorphology after birth. AIMS: To determine the effect of prenatal exposure to
      PCBs on cognitive development in Yucheng children. METHOD: One hundred and
      eighteen Yucheng children prenatally exposed to PCBs and degradation products,
      and community-matched control children who were exposed to background levels
      only, were followed from 1985 to 1998. The Bayley Scale for Infant Development,
      Chinese version of the Stanford-Binet IQ Test, Raven's Coloured Progressive
      Matrices and Raven's Standardised Progressive Matrices were used to assess the
      cognitive development of these children. RESULTS: The Yucheng children scored
      lower than control children on each of these methods of measurement between the
      ages of 2 and 12 years. CONCLUSIONS: Prenatal exposure to PCBs and their
      derivatives has long-term adverse effects on cognitive development in humans.

PMID- 11315226
TI  - Early-onset Alzheimer's disease in Scotland: environmental and familial factors.
AB  - BACKGROUND: Alzheimer's disease (AD) is a common, complex, age-related disorder
      in which both genetic and environmental factors are important. AIMS: To integrate
      recent studies on genetic and environmental factors in AD into a multi-factorial
      disease model. METHOD: Disease models to explain gene-environment interaction in
      cardiovascular disease are related to observations on AD. RESULTS: Informative,
      community-based studies on the genetic epidemiology of AD are rare. Putative risk
      factors from the Scottish studies include increased paternal age in AD men and
      coal mining as paternal occupation in both AD and vascular dementia. Migration
      effects suggest that environmental factors in high-incidence AD areas are
      important during adult life. CONCLUSIONS: The studies summarised do not provide
      sufficient data to support a single comprehensive disease model of gene
      environment interaction in AD. Future studies will require very large (> or =
      600) sample sizes, molecular genetic analysis, and environmental data that span
      neurodevelopment and the period between disease onset and appearance of clinical
      symptoms.

PMID- 11315227
TI  - Understanding the excess of psychosis among the African-Caribbean population in
      England. Review of current hypotheses.
AB  - BACKGROUND: Increased rates of schizophrenia continue to be reported among the
      African-Caribbean population in England. AIMS: To evaluate the competing
      biological, psychological and social explanations that have been proposed.
      METHOD: Literature review. RESULTS: The African-Caribbean population in England
      is at increased risk of both schizophrenia and mania; the higher rates remain
      when operational diagnostic criteria are used. The excess of the two psychotic
      disorders are probably linked: African-Caribbean patients with schizophrenia show
      more affective symptoms, and a more relapsing course with greater social
      disruption but fewer chronic negative symptoms, than White patients. No simple
      hypothesis explains these findings. CONCLUSIONS: More complex hypotheses are
      needed. One such links cultural variation in symptom reporting, the use of
      phenomenological constructs by psychiatrists and social disadvantage.

PMID- 11315228
TI  - Vulnerability factors for common mental illnesses.
AB  - BACKGROUND: Twin studies suggest that shared early family environment is of only
      minor importance in the aetiology of depression, most of the variance being
      attributable either to genetic or to individual 'non-shared' environmental
      factors. AIMS: To examine the respective roles of personality and social
      experiences on the risk for common mental disorders, with special reference to
      depression. METHOD: Analysis of preliminary findings from two large-scale British
      population surveys: (a) a multi-centre study of general practice patients, and
      (b) a study of working-class women in Manchester. RESULTS: (a) Persons recently
      separated from their partners have raised mean scores for psychological distress,
      but the relative excess is due entirely to persons with high ratings for
      introversion; (b) while severe life events were associated with physiological
      responses characteristic of depression, the probability of experiencing such life
      events varied between 0.2 monthly for low scorers and 1.5 monthly for high
      scorers on a vulnerability measure. CONCLUSIONS: Social factors do appear to
      influence the prevalence of depression, but this effect is not independent of
      genetically determined vulnerability.

PMID- 11315229
TI  - Neuroticism, life events and mental health: evidence for person-environment
      correlation.
AB  - BACKGROUND: There is some evidence that genetic effects on the likelihood of
      experiencing stressful life events (SLEs) are mediated by heritable traits such
      as cognitive ability (CA) and neuroticism (N). AIMS: To examine whether the
      association between CA, N and mental ill-health is driven in part by a
      predisposition to experience depressogenic SLEs. METHOD: Childhood measures of N
      and CA were available in a birth cohort of 5362 individuals. At ages 36 and 43
      years, mental state and occurrence of SLEs in the previous year were assessed.
      Using a path-analytic approach, models with and without a hypothesised influence
      of N and CA on the occurrence of SLEs were compared. RESULTS: The fit of the
      model with childhood N having a direct influence on SLEs was good with chi 2 =
      5.72, d.f. = 4, P = 0.22 at age 36 years and chi 2 = 3.50, d.f. = 5, P = 0.62 at
      age 43. The fit of the model was significantly worse without this path at both
      ages (36 years: chi 2 = 42.5, d.f. = 1, P < 0.001; 43 years chi 2 = 15.3, d.f. =
      1, P < 0.001). No consistent differences were seen in comparisons of models with
      CA. CONCLUSIONS: The results are congruent with the suggestion that genetic
      effects on SLEs are mediated by personal characteristics. Part of the well
      established association between N and minor psychiatric disorder may be mediated
      by an indirect effect of N on the likelihood of experiencing SLEs.

PMID- 11315230
TI  - Longitudinal study assessing the joint effects of socio-economic status and birth
      risks on adult emotional and nervous conditions.
AB  - BACKGROUND: Previous investigations into the impact of birth complications and
      social environment have generally followed their subjects only at young ages.
      AIMS: To assess the long-range impact of socio-economic status (SES) and birth
      risks on the development of emotional and nervous conditions through adulthood.
      METHOD: The Johns Hopkins Pathways Study interviewed 1824 subjects born between
      1960 and 1965. The median household income of the children at age 7-8 years was
      used to divide the cohort into high and low income categories. Differences in
      life time prevalence of emotional and nervous conditions through adulthood
      between the two income groups were identified. RESULTS: Children in the lower
      income group were 1.86 times more likely to report an emotional or nervous
      condition as adults. Boys in the lower income group at age 7-8 years were 3.2
      times more likely to do so. The risks of difficult birth for adult mental
      disturbance were accentuated in the low-income group. CONCLUSIONS: Children who
      experience birth complications are at increased risk of developing adult mental
      disturbances; this increase is mitigated by higher SES.

PMID- 11315231
TI  - The promise of psychiatric enviromics.
AB  - BACKGROUND: The human genome dwells within environment, determines environment
      and its expression is shaped by environment. AIMS: To introduce 'psychiatric
      enviromics' as a complement to human genomics and proteomics as applied to mental
      health. METHOD: Selective literature review and synthesis. RESULTS AND
      CONCLUSIONS: Psychiatric enviromics can be planned to sustain the search for
      specific environments or environmental processes and conditions that promote
      mental health and reduce the occurrence of psychiatric disturbances. Subsets of
      the psychiatric envirome will be discovered to have functional importance
      precisely because specific environmental conditions or processes will reduce,
      amplify or otherwise modulate the expression of specific genes or multiple gene
      interactions at identifiable periods of life-span development. Other salubrious
      environmental conditions and processes will have functional importance but lack
      specificity of action with respect to gene expression. An international
      collaboration in the form of a review of evidence is proposed as a starting point
      for 'psychiatric enviromics'.

PMID- 11315232
TI  - Inter-generational longitudinal study of social class and depression: a test of
      social causation and social selection models.
AB  - BACKGROUND: Generations of epidemiologists have documented an association between
      low socio-economic status (SES) and depression (variously defined), but debate
      continues as to which is the causative factor. AIMS: To test the extent to which
      social causation (low SES causing depression) and social selection (depression
      causing low SES) processes are in evidence in an inter-generational longitudinal
      study. METHOD: Participants (n = 756) were interviewed up to four times over 17
      years using the Schedule for Affective Disorders and Schizophrenia (SADS).
      RESULTS: Low parental education was associated with increased risk for offspring
      depression, even after controlling for parental depression, offspring gender and
      offspring age. Neither parental nor offspring depression predicted later levels
      of offspring occupation, education or income. CONCLUSION: There is evidence for
      an effect of parental SES on offspring depression (social causation) but not for
      an effect of either parental or offspring depression on offspring SES (social
      selection).

PMID- 11315233
TI  - Nature, nurture and mental disorder: old concepts in the new millennium.
AB  - BACKGROUND: Evidence from twin and adoption studies has highlighted the
      importance of gene-environment interaction in the aetiology of mental disorders,
      and advances in molecular genetics have raised hopes of more rapid progress in
      this field of investigation. AIMS: To review epidemiological knowledge concerning
      genetic and environmental risk factors for a cross-section of psychiatric
      conditions, and evidence of interaction between the two types. METHOD: Searches
      of the literature in genetic and psychiatric epidemiology, including
      contributions to this supplement. RESULTS: Overall, firm knowledge on both
      genetic and environmental causal factors is still fragmentary, although progress
      has varied among diagnostic categories. Environmental aspects have been dealt
      with only perfunctorily in most genetic epidemiological research. CONCLUSIONS:
      Better definition and classification of environmental hazards, and closer inter
      disciplinary cooperation, will be necessary in future. Specific gene-environment
      interaction effects seem likely to prove most important in neuropsychiatric
      syndromes, and a less specific genetic influence on susceptibility to
      environmental stress among the common mental disorders.

PMID- 11315234
TI  - Intermittent cyclic tiludronate in the treatment of osteoporosis.
AB  - The objective of the study was to determine the efficacy and safety of
      tiludronate in the treatment of postmenopausal osteoporosis. Two placebo
      controlled, randomized, double-masked, multicenter, cyclical, intermittent, dose
      ranging studies including 1805 women with low vertebral bone mineral density and
      prevalent vertebral fractures and 488 women with low bone mineral density and no
      prevalent fracture were conducted. Patients were randomized to either tiludronate
      50 mg/day, tiludronate 200 mg/day or placebo, given orally for the first 7 days
      of each month. A supplement of 500 mg elemental calcium was provided daily from
      day 8 to the end of the month. Both studies demonstrated no statistically or
      clinically relevant trends in the incidence of adverse effects across the three
      treatment groups. However, tiludronate administered at these two doses in a
      cyclic intermittent regimen was not effective in reducing the incidence of
      vertebral fractures or increasing spinal bone mineral density. Thus, tiludronate,
      administered at these doses in a cyclic intermittent regimen, cannot be
      considered an appropriate treatment of postmenopausal osteoporosis,
      notwithstanding a high safety profile.

PMID- 11315235
TI  - Hormonal and anthropometric predictors of bone mass in healthy elderly men: major
      effect of sex hormone binding globulin, parathyroid hormone and body weight.
AB  - Osteoporosis in men is a significant health problem, and factors associated with
      bone mass are being investigated. Although osteoporosis is a typical feature of
      hypogonadism, the influence of testosterone levels and other hormonal factors on
      bone mass of eugonadal males is unknown. Our aim was to identify several
      anthropometric and hormonal predictors that could be responsible for the
      variability in bone mineral density (BMD) in healthy men. One hundred elderly men
      (age 68 +/- 7 years) were investigated in this cross-sectional study. BMD was
      measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and
      femoral sites (femoral neck, Ward's triangle, trochanter, intertrochanter and
      total femur). Anthropometric measures were obtained including: weight, height,
      body mass index (BMI), waist-hip ratio and testicular volume. Hormonal data
      measures were total, free and bioavailable testosterone, dihidrotestosterone,
      estradiol, sex hormone binding globulin (SHBG), insulin-like growth factor I (IGF
      I), intact parathyroid hormone (iPTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3).
      One subject was excluded because primary hypogonadism was found. SHBG levels were
      increased in 53.5% of men, and 8% showed a mild increase in iPTH levels. Twenty
      eight subjects had densitometric criteria of osteoporosis (T-score < or = -2.5).
      All BMD sites were positively correlated with body weight (r = 0.29-0.48, p <
      0.001) and BMI (r = 0.24-0.47, p < 0.001). A negative correlation between SHBG
      levels and intertrochanter (IT) and total femur (TL) BMD was found (r = -0.24 and
      r = -0.22, p < 0.05). After adjusting for age and BMI, SHBG and IGF-I levels were
      negatively correlated (r = -0.33, p < 0.001). In multiple linear regression
      analysis independent predictors of bone mass were body weight, SHBG and iPTH
      levels. The best predictive model accounted for 24-40% of the observed
      variability of BMD. However, most of the BMD variability was explained by body
      weight. In conclusion, in our study body weight, SHBG and iPTH levels were
      predictors of BMD in healthy elderly men.

PMID- 11315236
TI  - DXA of the hip and heel ultrasound but not densitometry of the fingers can
      discriminate female hip fracture patients from controls: a comparison between
      four different methods.
AB  - Dual-energy X-ray absorptiometry (DXA) of the proximal femur and in more recent
      years quantitative ultrasound (QUS) of the heel are the most established methods
      for assessing hip fracture risk. Measurement of the fingers offers a new
      approach. We performed DXA of the proximal femur, QUS of the heel and fingers,
      and radiographic absorptiometry (RA) of the fingers in 87 non-institutionalized
      women, 65-85 years of age, with a first hip fracture and compared them with 195
      randomly selected age-matched controls. Bone mineral density (BMD) of the femoral
      neck and heel Stiffness Index were significantly lower among cases than among
      controls (by 15% and 17%, respectively; p < 0.0001), whereas no significant
      differences were found for finger measurements. When applying the WHO criterion
      of osteoporosis, 62-98% of the patients were classified as osteoporotic, compared
      with 19-85% of the controls, depending on method and site. The risks of hip
      fracture, estimated as odds ratios for every 1 SD reduction in femoral neck BMD,
      heel Stiffness Index, finger QUS and finger RA, were: 3.6 (95% CI 2.4-5.5), 3.4
      (95% CI 2.2-5.0), 1.0 (95% CI 0.7-1.3) and 1.2 (95% CI 0.8-1.6), respectively.
      Compared with women with normal BMD of the femoral neck, those classified as
      osteopenic had an odds ratio of hip fracture of 14 (95% CI 2-110), whereas those
      classified as osteoporotic had an odds ratio of 63 (95% CI 8-501). We conclude
      that hip DXA and heel QUS have similar capacities to discriminate the risk of a
      first hip fracture, whereas QUS and RA of the phalanges seem inferior techniques
      for differentiating female hip fracture patients from controls.

PMID- 11315237
TI  - The contribution of cortical and cancellous bone to dual-energy X-ray
      absorptiometry measurements in the female proximal femur.
AB  - Dual-energy X-ray absorptiometry (DXA) is the most common method for determining
      bone mineral density (BMD) in the proximal femur. However, there remain questions
      concerning the contribution of cortical and cancellous bone to this technology in
      the proximal femur. The purpose of this investigation was to identify structural
      and compositional characteristics of human bone in the proximal femur that
      significantly influence DXA BMD measurements. Twenty-four femora were obtained at
      autopsy from Caucasian females ranging in age from 17 to 92 years (mean +/- SD,
      61 +/- 25 years). DXA scans were performed on each specimen with a Hologic QDR
      2000 densitometer. Direct measurements were determined from proximal femoral
      sections for cancellous bone (volume fraction, ash fraction, cancellous cross
      sectional area and percent cancellous cross-sectional area), cortical bone
      (thickness, ash fraction, porosity, cortical cross-sectional area and percent
      cortical cross-sectional area) and anteroposterior thickness. These parameters
      were compared with the associated DXA measurements by means of simple and
      multiple regressions. Cancellous volume fraction was the best predictor of
      variability of DXA measurements for both the neck and trochanter, with an R2 of
      0.87 and 0.76, respectively (p < 0.0001). There was only a minor influence of
      cortical factors such as thickness (neck and trochanter R2 = 0.51 and 0.42,
      respectively, p < 0.001) and trochanteric cross-sectional area (R2 = 0.21, p <
      0.05). Although the accuracy for determining specific components of the proximal
      femur was low, the DXA BMD measurement was a strong predictor of cancellous bone
      factors, but not cortical bone factors that have been shown to change
      significantly with age.

PMID- 11315238
TI  - Bone mineral density during reduction, maintenance and regain of body weight in
      premenopausal, obese women.
AB  - Weight loss may lead to bone loss but little is known about changes in bone mass
      during regain of reduced weight. We studied changes in bone mineral density (BMD)
      and bone mineral content (BMC) during voluntary weight reduction and partial
      regain. The study consisted of three phases: a 3 month weight reduction with very
      low-energy diet (VLED), a 9 month randomized, controlled walking intervention
      period with two training groups (target energy expenditure 4.2 or 8.4 MJ/week)
      and a 24-month follow-up. The participants were premenopausal women with a mean
      body mass index of 34.0 (SD 3.6) kg/m2. Seventy-four of 85 subjects completed the
      whole study. Total body, lumbar spine, proximal femur and dominant radius BMD and
      BMC were measured with dual-energy X-ray absorptiometry (DXA). The mean weight
      loss during VLED was 13.2 (3.4) kg, accompanied by unchanged total body BMC and
      decreased lumbar, trochanteric and radial BMD (p < 0.05). During months 3-36, an
      average of 62% of the weight loss was regained, total body BMC decreased and
      trochanteric BMD increased (p < 0.05). At the end of the study, total body BMC
      and lumbar and femoral neck BMD were lower than initially (p < 0.05). Weight
      change throughout the study correlated significantly with the change in radial (r
      = 0.54), total body (r = 0.39) and trochanteric (r = 0.37) BMD. Exercise-group
      assignment had no effect on BMD at weight-bearing sites. In conclusion, the
      observed changes in BMD and BMC during weight reduction and its partial regain
      were clinically small and partly reversible. More studies are needed to clarify
      whether the observed weight changes in BMD and BMC are real or are artifacts
      arising from assumptions, inaccuracies and technical limitations of DXA.

PMID- 11315239
TI  - Acute and long-term increase in fracture risk after hospitalization for vertebral
      fracture.
AB  - The aims of this study were to determine the magnitude of the increase in risk of
      further fracture following hospitalization for vertebral fracture, and in
      particular to determine the time course of this risk. The records of the Swedish
      Patient Register were examined from 1987 to 1994 to identify all patients who
      were admitted to hospital for thoracic or lumbar vertebral fractures. Vertebral
      fractures were characterized as due to high- or low-energy trauma. Patients were
      followed for subsequent hospitalizations for hip fracture, and for all fractures
      combined. A Poisson model was used to determine the absolute risk of subsequent
      nonvertebral fracture and compared with that of the general population. We
      analyzed 13.4 million hospital admissions from which 28,869 individuals with
      vertebral fracture were identified, of which 60% were associated with low-energy
      trauma. There was a marked increase in subsequent incidence of hip and all
      fractures within the first year following hospitalization for vertebral fracture
      in both men and women. Thereafter, fracture incidence declined toward, but did
      not attain, baseline risk. Increased risks were particularly marked in the young.
      The increase in fracture risk was more marked following low-energy vertebral
      fracture than in the case of high-energy trauma. We conclude that the high
      incidence of new fractures within a year of hospitalization for vertebral
      fractures, irrespective of the degree of trauma involved, indicates that such
      patients should be preferentially targeted for treatment. It is speculated that
      short courses of treatment at the time of first vertebral fracture could provide
      important therapeutic dividends.

PMID- 11315240
TI  - Hip fracture prevention trial using hip protectors in Japanese nursing homes.
AB  - A method to protect the hips during falls could effectively reduce the incidence
      of hip fractures. We report the results of the first hip protector trial in
      Japan, performed between July 1996, and September 1999. One hundred and sixty
      four elderly female residents of nursing homes, with Activities of Daily Living
      above the wheelchair level, agreed to participate in this study. Among them, 88
      were randomly selected to wear a hip protector and 76 controls did not. All falls
      and resulting injuries were recorded daily. In anthropometric measurements and
      ultrasonic bone evaluation, no significant differences were found between the two
      groups, except in height. During an average of 377 days, the wearers and the non
      wearers fell a total of 131 and 90 times, respectively. Among the wearers, there
      were two non-hip fractures and one hip fracture, so the annual hip fracture rate
      was calculated at 1.2%, against 8 hip fractures among the non-wearers, or 9.7%
      per year. The hip fracture rate was significantly lower among the wearers than
      non-wearers, while the annual number of falls per subject and the distribution of
      fallers remained the same. According to Cox's proportional hazard regression
      analysis, the effect of the hip protector on hip fracture prevention was
      independent of anthropometric data, ultrasonic bone assessment values or number
      of falls. Moreover, even after limiting the subjects to fallers only, the annual
      hip fracture rate in non-wearers was higher than in wearers (19.8% vs 2.0%) and
      the annual hip fracture rate per fall in wearers was lower than that in non
      wearers (0.8% vs 8.2%). It was thus concluded that the hip protector is a
      beneficial device for the prevention of hip fractures.

PMID- 11315241
TI  - How do reproductive and lifestyle factors influence bone density in distal and
      ultradistal radius of early postmenopausal women? The Nord-Trondelag Health
      Survey, Norway.
AB  - In a population-based health survey, densitometry was performed at the distal and
      ultradistal radius with single-energy X-ray absorptiometry. Bone mineral density
      (BMD) data and self-reported reproductive and lifestyle data from 1652 randomly
      selected peri- and postmenopausal women aged 50-59 years were analyzed. A total
      of 893 (54.1%) postmenopausal women reported no prior use of hormone replacement
      therapy (HRT) and constituted the principal group of study. These women were more
      frequently smokers, consumed less alcohol, more coffee and had made less use of
      oral contraceptives (OC) than women in the HRT group. The strongest association
      with both distal and ultradistal radius bone densities was found for age, weight,
      time since menopause and a history of bilateral oophorectomy. Among reproductive
      factors, nulliparous women had lower BMD than parous women; however, no linear
      relationship was found between parity and bone density. A weak, positive
      relationship was found for OC and BMD in bivariate, but not in multivariate
      analyses. A history of hysterectomy was positively associated with BMD, stronger
      at the ultradistal than distal radius. A positive relationship between alcohol
      consumption and BMD was found at the ultradistal radius. Present or prior smokers
      had lower BMD than never smokers. In the multivariate model, interaction between
      pack-years of smoking and daily coffee intake was observed at the distal radius,
      and both factors had a stronger negative influence on distal than ultradistal
      radius bone density. In perimenopausal women, most reproductive and lifestyle
      risk factors found to be associated with BMD of the radius may be explained by
      different levels of estrogen.

PMID- 11315242
TI  - Peripubertal moderate exercise increases bone mass in boys but not in girls: a
      population-based intervention study.
AB  - On the basis of cross-sectional studies in elite athletes and longitudinal
      studies, physical activity in growing children has been suggested to enhance bone
      mineral acquisition and prevent osteoporosis later in life. The level of exercise
      in most of these studies is not applicable in a population on a day-to-day basis.
      The aim of this study was to determine whether moderate increased exercise within
      the school curriculum from age 12 to 16 years would have anabolic bone effects.
      In a population-based setting of 40 boys and 40 girls the school curriculum was
      enhanced to physical education 4 times per week for 3-4 years. Controls were 82
      boys and 66 girls who had had physical education twice a week over a
      corresponding period. Both cases and controls were measured at age 16 years. Bone
      mineral content (BMC), areal bone mineral density (aBMD), bone size (femoral neck
      width) and volumetric BMD (vBMD) were measured in total body, spine and femoral
      neck (FN) by dual-energy X-ray absorptiometry. Data are presented as mean +/- SD.
      BMC (8 +/- 15%, p = 0.04), aBMD (9 +/- 13%, p = 0.002) and vBMD (9 +/- 15%, p =
      0.001) were all higher in FN in the male intervention group compared with
      controls. FN bone size was no higher in the intervention group than in the
      controls. In girls, no differences were found when comparing the intervention
      group with controls. The results remained after adjusting for confounding factors
      such as weight, height, milk intake and activity after school. In summary, we
      report that increased bone mass can be achieved in a population-based cohort of
      boys (but not in girls) by moderate increased physical activity within the school
      curriculum from age 12 to 16 years. We speculate that the same results can be
      seen in girls if intervention starts at an earlier age. We conclude that
      increasing the physical education content of the Swedish school curriculum may
      improve bone mass in at least peripubertal boys.

PMID- 11315243
TI  - The incidence of hip fracture in four Asian countries: the Asian Osteoporosis
      Study (AOS).
AB  - The Asian Osteoporosis Study (AOS) is the first multicenter study to document and
      compare the incidence of hip fracture in four Asian countries. Hosital discharge
      data for the year 1997 were obtained for the Hong Kong SAR, Singapore, Malaysia
      and Thailand (Chiang Mai). The number of patients who were 50 years of age and
      older and who were discharged with a diagnosis of hip fracture (ICD9 820) was
      enumerated. The age-specific incidence rates were deduced and were directly
      adjusted to the US white population in 1989. The age-adjusted rates for men and
      women (per 100,000) are as follows: Hong Kong, 180 and 459; Singapore, 164 and
      442; Malaysia, 88 and 218; Thailand, 114 and 289; compared with US White rates of
      187 in men and 535 in women, published in 1989. We conclude that there is
      moderate variation in the incidence of hip fracture among Asian countries. The
      rates were highest in urbanized countries. With rapid economic development in
      Asia, hip fracture will prove to be a major public health challenge.

PMID- 11315244
TI  - Physical activity and risk factors for hip fractures in Thai women.
AB  - Hip fractures are among the most important causes of ill health and death among
      elderly people. Several potentially modifiable risk factors have been reported.
      Most claimed physical activity as a promising, inexpensive preventive measure for
      hip fracture. However, knowledge about risk factors for hip fracture in Asian
      populations is very limited. We therefore conducted a case-control study to
      assess the relationships between physical activity and risk of hip fractures in
      Thai women. From 14 hospitals in Thailand, 229 cases with a radiologically
      confirmed first hip fracture were enrolled. Two hundred and twenty-four controls
      were randomly recruited from the same neighborhood and were matched to the cases
      by age within a 5 year range. Information on physical activity as well as other
      potential confounders was obtained through personal interviews. Multivariate
      logistic regression revealed that past physical activity was protective in both
      very active and active women (OR = 0.67, 95% CI = 0.40-1.12 for moderately active
      women and OR = 0.20, 95% CI = 0.10-0.38 for very active women; p value for trend
      < 0.01). Recent physical activity reduced the risk to about two-thirds (OR =
      0.33, 95% CI = 0.19-0.60 and OR = 0.35, 95% CI = 0.18-0.69 for moderately and
      very active women respectively). In addition, breastfeeding was identified to be
      a protective factor (OR = 0.87, 95% CI = 0.80-0.94). In contrast, the following
      risk factors were identified: current use of antihistamine (OR = 13.96, 95% CI =
      1.38-141.13) or traditional medicine (OR = 7.66, 95% CI = 2.71-21.63), underlying
      cerebrovascular diseases (OR = 6.53, 95% CI = 2.10-20.34), history of fracture
      (OR = 4.04, 95% CI = 1.26-12.99), parental Chinese racial background (OR = 2.52,
      95% CI = 1.49-4.23), alcohol consumption (OR = 2.30, 95% CI = 1.04-5.09).

PMID- 11315245
TI  - The bone mineral density of the right and left femur in a large group of white
      women.

PMID- 11315246
TI  - Sociopolitical diversity in psychology. The case for pluralism.
AB  - Psychology celebrates diversity, recognizes the value and legitimacy of diverse
      beliefs, and strives to be inclusive. Yet, the profession lacks sociopolitical
      diversity. Most psychologists are politically liberal, and conservatives are
      vastly underrepresented in the profession. Moreover, when sociopolitical views
      guide the research, advocacy, or professional practice of psychologists, those
      views most often are liberal. The lack of political diversity in psychology has
      unintended negative consequences for research, policy advocacy, clinical
      practice, the design and implementation of social interventions, and professional
      education. It excludes or marginalizes conservatives and conservative views,
      having detrimental effects on the profession in each of these areas. This article
      examines the importance of political diversity and the negative consequences of
      its absence and provides strategies for increasing sociopolitical pluralism in
      psychology.

PMID- 11315247
TI  - Why positive psychology is necessary.
AB  - The authors provide a definition of positive psychology and suggest that
      psychologists should try to cultivate a more appreciative perspective on human
      nature. Examples are given of a negative bias that seems to pervade much of
      theoretical psychology, which may limit psychologists' understanding of typical
      and successful human functioning. Finally, a preview of the articles in the
      special section is given.

PMID- 11315249
TI  - Ordinary magic. Resilience processes in development.
AB  - The study of resilience in development has overturned many negative assumptions
      and deficit-focused models about children growing up under the threat of
      disadvantage and adversity. The most surprising conclusion emerging from studies
      of these children is the ordinariness of resilience. An examination of converging
      findings from variable-focused and person-focused investigations of these
      phenomena suggests that resilience is common and that it usually arises from the
      normative functions of human adaptational systems, with the greatest threats to
      human development being those that compromise these protective systems. The
      conclusion that resilience is made of ordinary rather than extraordinary
      processes offers a more positive outlook on human development and adaptation, as
      well as direction for policy and practice aimed at enhancing the development of
      children at risk for problems and psychopathology.

PMID- 11315248
TI  - The role of positive emotions in positive psychology. The broaden-and-build
      theory of positive emotions.
AB  - In this article, the author describes a new theoretical perspective on positive
      emotions and situates this new perspective within the emerging field of positive
      psychology. The broaden-and-build theory posits that experiences of positive
      emotions broaden people's momentary thought-action repertoires, which in turn
      serves to build their enduring personal resources, ranging from physical and
      intellectual resources to social and psychological resources. Preliminary
      empirical evidence supporting the broaden-and-build theory is reviewed, and open
      empirical questions that remain to be tested are identified. The theory and
      findings suggest that the capacity to experience positive emotions may be a
      fundamental human strength central to the study of human flourishing.

PMID- 11315250
TI  - Why are some people happier than others? The role of cognitive and motivational
      processes in well-being.
AB  - Addressing the question of why some people are happier than others is important
      for both theoretical and practical reasons and should be a central goal of a
      comprehensive positive psychology. Following a construal theory of happiness, the
      author proposes that multiple cognitive and motivational processes moderate the
      impact of the objective environment on well-being. Thus, to understand why some
      people are happier than others, one must understand the cognitive and
      motivational processes that serve to maintain, and even enhance, enduring
      happiness and transient mood. The author's approach has been to explore
      hedonically relevant psychological processes, such as social comparison,
      dissonance reduction, self-reflection, self-evaluation, and person perception, in
      chronically happy and unhappy individuals. In support of a construal framework,
      self-rated happy and unhappy people have been shown to differ systematically in
      the particular cognitive and motivational strategies they use. Promising research
      directions for positive psychology in pursuit of the sources of happiness, as
      well as the implications of the construal approach for prescriptions for
      enhancing well-being, are discussed.

PMID- 11315251
TI  - In search of realistic optimism. Meaning, knowledge, and warm fuzziness.
AB  - Is it better to be realistic or optimistic? A realistic outlook improves chances
      to negotiate the environment successfully, whereas an optimistic outlook places
      priority on feeling good. But are realistic and optimistic outlooks necessarily
      in conflict? The author suggests that the fuzzy nature of accuracy typically
      places only loose boundaries on what it means to be realistic. As a result, there
      are many forms of optimism that do not, in principle, yield unrealistic
      assessments. Nevertheless, there remain numerous "optimistic biases" that do
      involve self-deception, or convincing oneself of desired beliefs without
      appropriate reality checks. The author describes several ways that realistic and
      unrealistic optimism can be differentiated and explores the impact of this
      distinction for current views of optimism. This critique reveals how positive
      psychology may benefit from a focus on personal meaning and knowledge as they
      relate to making the most of life.

PMID- 11315252
TI  - Get a surgeon, hold the cardiologist: electrocardiogram falsely suggestive of
      myocardial infarction in acute cholecystitis.

PMID- 11315253
TI  - Use of caffeine in post-dural puncture headache: a case report.

PMID- 11315254
TI  - Gastric adenocarcinoma: pathomorphology and molecular pathology.
AB  - Two types of gastric adenocarcinoma can be distinguished histopathologically: the
      diffuse and the intestinal type. Molecular pathology supports this theory by
      showing differences in the genetic pathways of both tumor types. In addition to
      known pathomorphological factors of prognosis, e.g., depth of tumor infiltration,
      number of lymph node metastases and resection margins, a few genes have been
      suggested to have prognostic impact in gastric carcinoma. Clinically relevant
      molecules whose expression or structure is altered include the plasminogen
      activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1),
      the cell cycle regulator cyclin E, epidermal growth factor (EGF), the apoptosis
      inhibitor bcl-2, the cell adhesion molecule E-cadherin, and the multifunctional
      protein beta-catenin. Gene amplification and protein overexpression of the growth
      factor receptors c-erbB-2 and K-sam may be prognostic factors for intestinal-type
      and diffuse-type gastric cancer, respectively. In addition, genetic instability
      is commonly seen. There has long been evidence for a genetic predisposition to
      gastric cancer by epidemiological studies and case reports. Very recently, germ
      line mutations of E-cadherin have been identified that are responsible for a
      dominantly inherited form of diffuse-type gastric cancer and could be used to
      identify individuals that are at high risk.

PMID- 11315255
TI  - Treatment of malignant glioma: a problem beyond the margins of resection.
AB  - The treatment of malignant glioma remains problematic. Surgical removal followed
      by external beam irradiation represents a standard treatment that has
      demonstrated a prolonged time to progression and survival. However, the capacity
      to locally invade normal brain invariably leads to formation of a recurrent tumor
      most often immediately adjacent to the site of resection. This clinical everyday
      experience prompts the hypothesis that improved local control of the tumor may
      translate into a delayed time to progression and possibly survival, specifically
      because systemic chemotherapy for most of these tumors has failed to
      significantly improve survival. Local treatment strategies including
      chemotherapy, gene therapy, and immunotherapy are rapidly developing and
      progressing to clinical trials. Several theoretical considerations suggest that
      these approaches may be promising in the treatment of brain tumors.

PMID- 11315256
TI  - Elevated activity and expression of Src-family kinases in human breast carcinoma
      tissue versus matched non-tumor tissue.
AB  - Src-family kinase expression was measured in 52 human mammary tumor (T) specimens
      compared with non-tumor (NT) tissue from the same patient by enzymatic assays
      employing a Src-kinase family-specific peptide substrate and by immunoblotting
      with an antibody recognizing the Src-family kinases Src, Fyn, and Yes. In the T
      specimens, the mean enzymatic activity was moderately elevated (T: 160 fmol ATP
      min-1 mg-1; NT: 115 fmol ATP min-1 mg-1) with 25 tumor samples having higher
      activity than the corresponding NT tissue, 17 having lower activity, and no
      activity detectable in ten T/NT pairs. Immunoblotting revealed clearly elevated
      expression in 25 tumor tissues and no differences or expression below the
      detection limit in the remaining T/NT pairs. The data are in agreement with a
      possible role of Src-family kinases for the biology of mammary carcinoma.

PMID- 11315257
TI  - Relationship between metastasis-associated phenotypes and N-glycan structure of
      surface glycoproteins in human hepatocarcinoma cells.
AB  - PURPOSE: To study the relation of N-glycan structure on cell surface
      glycoproteins to the metastatic phenotypes. METHODS: Two human hepatocarcinoma
      7721 cell lines transfected with sense or antisense cDNA of GnT-V, named GnT
      V/7721 and GnT-V-AS/7721, respectively, were adopted, because GnT-V can change
      the antennary number and the content of the beta 1,6 GlcNAc branch in N-glycans.
      The effects of over- and under-expression of GnT-V on the metastasis-associated
      phenotype of the transfected cells were investigated and compared with the cells
      mock-transfected with the plasmid vector. RESULTS: In GnT-V/7721 cells, GnT-V
      activity was increased by 92% compared with the mock cells. HRP-labeled lectin
      staining of transfected cells showed elevated intensity with HRP-L-PHA and
      reduced intensity with HRP-ConA, suggesting the increased antennary number and
      content of the beta 1,6 GlcNAc branch in N-glycans. Analysis of the N-glycan
      structure of [3H]-labeled glycopeptides prepared from cell-surface [3H]
      glycoproteins using DSA-affinity chromatography also revealed the above change of
      the N-glycan structure in a more quantitative manner. GnT-V/7721 cells showed a
      suppressed cell attachment to fibronectin (Fn) or laminin (Ln), and increased
      cell migration and invasion through matrigel. In contrast, GnT-V-AS/7721 cells
      showed reduction of both GnT-V activity and content of the beta 1,6 branch in N
      linked glycans, elevation of cell attachment to Fn or Ln, and decline of cell
      migration and invasion through matrigel. These changes were just the opposite to
      those in GnT-V/7721 cells. CONCLUSIONS: The alteration of N-glycan structure in
      surface glycoproteins resulting from the activity change of GnT-V contributes to
      the alterations in metastasis-associated phenotypes. The product of GnT-V, the
      beta 1,6 GlcNAc branch in N-linked glycans, is a structural factor of adhesion
      inhibition and invasion promotion. GnT-V is, therefore, closely related to cancer
      metastasis and its over-expression is an important molecular mechanism of
      metastasis.

PMID- 11315258
TI  - Differential expression of retinoic acid receptors and p53 protein in normal,
      premalignant, and malignant esophageal tissues.
AB  - PURPOSE: Esophageal cancer remains a significant health problem worldwide. The
      very low 5-year survival rates and rapid increase in the incidence of
      adenocarcinoma indicate the urgent need for early identification of and new
      approaches to the prevention and treatment of this cancer. METHODS: To find
      biomarkers for early identification of the disease, we analyzed nuclear retinoic
      retinoid receptor mRNAs, p53 protein, and the proliferation marker Ki 67 in
      surgical specimens of normal, mildly, and severely dysplastic and malignant
      esophageal tissues. RESULTS: Nuclear retinoid receptors (RAR-alpha, RAR-gamma,
      and RXR-alpha) were expressed in most (79%-100%) normal, dysplastic, and
      malignant esophageal mucosae, whereas expression of RAR-beta was progressively
      lost from normal esophagus to carcinoma (84%-54%). In contrast, expression of p53
      protein and Ki 67 were dramatically increased in severely dysplastic and
      cancerous tissues of the esophagus (from 5% to 62%). CONCLUSIONS: Loss of RAR
      beta expression and accumulation of p53 and Ki 67 proteins may serve as
      biomarkers for esophageal cancer.

PMID- 11315259
TI  - High-dose chemotherapy with peripheral blood stem cell transplantation for
      patients with advanced ovarian cancer.
AB  - PURPOSE: We report the results of high-dose chemotherapy (HDC) with peripheral
      blood stem cell transplantation in twenty-one patients with primarily advanced or
      relapsed ovarian cancer. METHODS: Twenty-five women underwent stem cell
      collection, and 21 were finally treated with different regimens of HDC containing
      cyclophosphamide, etoposide, carboplatin, and treosulfan. The patients received
      cyclophosphamide +/- cisplatin and cisplatin + paclitaxel, respectively, followed
      by G-CSF (n = 24) or GM-CSF (n = 1) for stem cell mobilization. RESULTS: A mean
      of 7.2 +/- 6.1 x 10(6) CD34+ cells per kg bw were collected. Thirteen patients
      received double transplants and one patient received a triple transplant. The
      median age was 47 years (range 24-61 years) and the mean number of prior regimens
      was three (range 1-8). Engraftment occurred on time in all patients and there was
      one treatment-related death resulting in an overall mortality rate of 4.8% among
      the 21 patients treated with HDC. The response rate was 72% (48% CR, 24% PR) and
      the mean time to progression and overall survival after HDC were 7 and 32 months,
      respectively. CONCLUSION: HDC could be performed safely in patients with advanced
      ovarian cancer. However, even with a high response rate, the duration of response
      is short, warranting new treatment approaches to further improve the outcome of
      this population of patients with unfavorable prognosis.

PMID- 11315260
TI  - Alterations in cyclin D1 expression in esophageal squamous cell carcinoma in the
      Indian population.
AB  - PURPOSE: The p16/cyclin D1/pRb pathway plays a critical role in tumourigenesis.
      We recently reported alterations in expression of tumour suppressor gene
      products, p16 and pRb in esophageal cancer. Knowledge of alterations in cyclin
      D1, a vital component of this pathway in esophageal carcinomas from the Indian
      subcontinent, where the etiology and pathogenesis may be confounded by various
      unique dietary and environmental factors, is presently scanty. In order to bridge
      the gap between the accentuating incidence of esophageal cancer and aberrations
      in the components of this vital pathway, we analysed cyclin D1 expression in
      esophageal squamous cell carcinoma in the Indian population. METHOD:
      Immunohistochemical analysis of cyclin D1 expression was carried out in paraffin
      embedded sections of surgically resected esophageal squamous cell carcinomas
      (ESCC) (70 patients) and matched with histopathologically normal esophageal
      tissues from a distant site. The findings were correlated with
      clinicopathological parameters. RESULTS: Overexpression of cyclin D1 was observed
      in the tumour nuclei in 41 out of 70 (59%) patients. We found concomitant
      alterations in 16 and cyclin D1 (p16-/CycD1+ phenotype) in 16 of the 70 patients
      (23%), while alterations of pRb and cyclin D1 (pRb-/CycD1+) were observed in 36
      of the 70 (51%) patients of ESCCs. Cyclin D1 overexpression was significantly
      associated with the loss of p16 immunoreactivity (P = 0.005). The pRb- and p16
      /pRb-/Cyc D+ phenotypes showed significant association with differentiation of
      the tumour (P = 0.005, 0.05, respectively). Kaplan-Meier analysis for disease
      recurrence showed increased disease recurrence in cyclin D1 overexpressed
      patients. Median time to disease recurrence in the cyclin D1+ group was 15 months
      as against 18 months observed in the cyclin D1- patients (P = 0.067; log-rank
      test). CONCLUSION: Alterations in at least one of the components of the
      p16/cyclin D1/pRb pathway in majority of the 70 patients analysed herein, and
      concomitant alterations in all the three proteins in 19 patients (35%) underscore
      the critical role of this pathway in esophageal tumourigenesis. The results of
      the present study taken together with our previous findings on p16 and pRb
      alterations in ESCCs suggest that these alterations are not mutually exclusive
      and may cooperatively provide greater tumour growth advantage. The prognostic
      significance of alterations in the expression of these components cyclin D1, p16,
      and pRb remains to be established in a larger cohort.

PMID- 11315261
TI  - Resveratrol inhibits human breast cancer cell growth and may mitigate the effect
      of linoleic acid, a potent breast cancer cell stimulator.
AB  - Resveratrol is a naturally occurring product found in grapes and wine. The effect
      of synthetic resveratrol on the growth of estrogen receptor (ER)-positive (KPL-1
      and MCF-7) and -negative (MKL-F) human breast cancer cell lines was examined.
      Resveratrol at low concentrations caused cell proliferation in ER-positive lines
      (KPL-1, < or = 22 microM; MCF-7, < or = 4 microM) whereas at high concentrations
      (> or = 44 microM) it caused suppression of cell growth in all three cell lines
      examined. Growth suppression was due to apoptosis as seen by the appearance of a
      sub-G1 fraction. The apoptosis cascade up-regulated Bax and Bak protein, down
      regulated Bcl-xL protein, and activated caspase-3. Resveratrol (52-74 microM)
      antagonized the effect of linoleic acid, a potent breast cancer cell stimulator,
      and suppressed the growth of both ER-positive and -negative cell lines. Thus,
      resveratrol could be a promising anticancer agent for both hormone-dependent and
      hormone-independent breast cancers, and may mitigate the growth stimulatory
      effect of linoleic acid in the Western-style diet.

PMID- 11315262
TI  - Renal cell cancer correlated with occupational exposure to trichloroethylene.

PMID- 11315263
TI  - Azygos vein anomaly: the best predictor of a long gap in esophageal atresia and
      tracheoesophageal fistula.
AB  - The gap between the pouches has a direct bearing on the tension at the
      anastomosis that ultimately determines the anastomotic leak in esophageal atresia
      with or without tracheoesophageal fistula (EA-TEF). Long-gap EA has been reported
      to be associated with aortic-arch anomalies and 13 pairs of ribs. Our observation
      that EA-TEF with an azygos-vein anomaly (AVA) invariably had a long gap led us to
      retrospectively analyze our data. The mean gaps (+/- SD) in the groups with 13
      pairs of ribs (n = 6), right-sided aortic arch (n = 16), and AVA (n = 9) were
      1.25 +/- 0.27, 2.18 +/- 0.98, and 3.16 +/- 0.16 cm, respectively. There was no
      statistically significant difference in the gap in patients who had 13 pairs of
      ribs compared with controls who had 12 pairs of ribs. The gap was highest in the
      AVA group and was statistically significant (P < 0.001) compared with patients
      with a normal azygos vein. In addition, the AVA group had a significant increase
      in mortality (P < 0.05) compared to the groups with a normal azygos vein;
      although there was no statistically significant difference in other factors:
      birth weight, time between delivery and surgery, cardiac anomalies, anorectal
      malformations, renal malformations, and chest infection in the AVA group and
      controls. An extra pair of ribs is not associated with a long gap, and an AVA per
      se is an independent predictor of a long gap and mortality in EA-TEF.

PMID- 11315264
TI  - Are stable postoperative biliary atresia patients really stable?
AB  - Transforming growth factor-beta 1 (TGF beta-1) is an important mediator of liver
      cell proliferation and replication that is implicated in hepatic fibrosis (HF).
      Hepatic stellate cells (HSC) are activated by TGF beta-1 and are the main
      precursor cells involved in fibrogenesis. The correlation between serum TGF beta
      1, activated HSC in liver-biopsy specimens, and liver biochemistry was
      investigated to determine the value of TGF beta-1 as an indicator of clinical
      status in postoperative biliary atresia (BA) patients. Thirty-two postoperative
      BA patients (mean age 11.2 +/- 2.8 years) and 13 normal controls (mean age 10.3
      +/- 3.7 years) were studied. Based on average liver function test (LFT) results
      over a 3-month period immediately prior to this study, the BA patients were
      divided into group I (anicteric, normal LFT; n = 10); group II (anicteric,
      elevated liver transaminases; n = 12), and group III (jaundiced end-stage liver
      fibrosis awaiting liver transplantation; n = 10). Serum TGF beta-1 was determined
      using ELISA. Liver-biopsy specimens were examined with antibody against TGF beta
      1 and alpha-smooth muscle actin (SMA) antibody for detection of activated HSC.
      Serum TGF beta-1 was significantly higher in groups I (11.4 +/- 3.7 ng/ml; P <
      0.01) and II (23.3 +/- 11.3 ng/ml; P < 0.001) than in group III (3.0 +/- 1.5
      ng/ml) and controls (4.5 +/- 2.5 ng/ml) despite normal LFT in group I. The 3
      subjects with the highest serum TGF beta-1 in group II had bile lakes. Biopsies
      from groups I and II were strongly positive for TGF beta-1 in hepatocytes and
      Kupffer cells and for activated HSC detected by SMA compared with group III and
      controls. Because serum TGF beta-1 and activated HSC are only present during
      active fibrosis, we conclude that there is progressive fibrogenesis even in
      seemingly normal postoperative BA patients. In particular, bile lakes should be
      regarded as a key sign of progressive HF, the presence of which should be
      regarded with extreme caution. We suggest that serum TGF beta-1 could be used as
      an accurate indicator of progressive fibrogenesis in postoperative BA patients.

PMID- 11315265
TI  - Cholangitis associated with cystic dilatation of the intrahepatic bile ducts
      after antireflux valve construction in biliary atresia.
AB  - An intussusception-type antireflux valve (ARV) has been introduced to prevent
      postoperative ascending cholangitis in the management of biliary atresia (BA). We
      investigated the characteristics of cholangitis in the management of BA using the
      ARV in 38 patients who had undergone an operation at our institution; 29
      underwent ARV construction at the same time as portenterostomy (PEO) or
      hepaticojejunostomy. One patient underwent ARV construction for refractory
      cholangitis with cystic dilatation of the intrahepatic bile ducts (CDIB) long
      after the PEO. Five of 29 patients who had ARV construction developed CDIB
      complicated by severe, refractory cholangitis. One or two episodes of mild
      cholangitis were observed in 5 (20.8%) of 24 patients who did not show CDIB. An
      ARV created for postoperative recurrent cholangitis associated with CDIB was
      ineffective. Preoperative cholangitis associated with a type I choledochal cyst
      and CDIB was observed in 1 patient. In conclusion, the ARV was effective in
      preventing refractory cholangitis without CDIB, but ineffective in preventing
      cholangitis with CDIB. Our findings suggest that CDIB resulting from the ongoing
      process of BA could be a potential target of bacterial infection through other
      routes than bilioenteric reflux.

PMID- 11315266
TI  - Diagnostic dilemmas in abdominal tuberculosis in children.
AB  - The authors review 45 pediatric patients with intra-abdominal tuberculosis (ATB)
      treated between May 1990 and April 1998. The diagnosis was confirmed
      histologically or by positive culture for Mycobacterium tuberculosis. Clinical
      presentation was with an abdominal mass (12), subacute obstruction (11), ascites
      (5), mass and ascites (4), peritonitis (4), and 9 unusual presentations. Mantoux
      tests were positive in 68% of patients tested. There were radiologic features
      suggestive of pulmonary TB in 29 patients (64%); abnormal abdominal radiographs
      were recorded in 21 (47%). Lymphadenopathy was noted on abdominal ultrasound in
      23 of 30 patients (77%) and on computed tomography scan in a further 3 of 8
      patients investigated. Ascitic fluid adenosine deaminase (ADA) levels were
      greater than 30 IU/l in 3 of 4 patients (75%), suggesting ATB. All 28 patients
      screened for human immunodeficiency virus were negative. A surgical procedure was
      performed in 39 patients. 29 (74%) had an elective diagnostic laparotomy for
      tissue diagnosis. One (3.4%) developed a postoperative intra-abdominal abscess.
      Ten (26%) presented with complications requiring surgical intervention including
      perforated viscus, segmental bowel resection, strictureplasty, adhesiolysis, or
      ileostomy. One of the latter died due to sepsis after having complications of
      persistent intestinal obstruction and cecal perforation. The authors recommend an
      aggressive approach to patients with suspected ATB in order to obtain an early
      definitive diagnosis, prevent complications, and reduce morbidity and mortality.
      They emphasize the importance of tissue diagnosis and confirmation by culture.

PMID- 11315267
TI  - Intestinal damage in gastroschisis is independent of the size of the abdominal
      defect.
AB  - The intestinal damage in gastroschisis (GS) has been attributed to a narrow
      abdominal wall defect (AWD), among other causes, but this causal effect is
      difficult to prove in humans. The present experimental study was done to
      ascertain the damaging effect of clinically extrapolable mild and moderate
      constriction at the AWD on the intestine of fetuses with GS. AWDs of two
      different sizes were carried out in the fetal rabbit model: small-ring GS (1.5x
      bowel diameter, SRG) and large-ring GS (3x bowel diameter, LRG); a group of
      unoperated littermates served as controls. Fetal body weight, intestinal length
      and weight, bowel diameter and wall thickness, and histology were checked 7 days
      later. No statistical difference was found in body weight and bowel diameter
      among the groups. Intestinal length, weight, and wall thickness were
      significantly different in the GS groups compared to the controls, but no
      difference was found between the GS groups. Histology did not show venous stasis,
      ischemic lesions, or differences in the degree of edema between groups SRG and
      LRG. Mesothelial hyperplasia was seen in both GS groups. The intestinal changes
      in length, weight, diameter, wall thickness, and histology in GS should thus not
      be attributed to the diameter of the AWD.

PMID- 11315268
TI  - Intra-operative pulse oximetry can help determine intestinal viability.
AB  - The intra-operative assessment of intestinal viability when dealing with
      ischaemic bowel remains a challenge. Reliable healing of small-bowel anastomoses,
      using pulse oximetry to exclude critical ischaemia, has been shown in the canine
      model. In this study, intra-operative pulse oximetry (PO) was used to help
      determine intestinal viability 48 h after de-torsion of a volvulus. Approximately
      one-half of the ischaemic, volved bowel was able to be preserved. Intra-operative
      PO can thus help preserve bowel of doubtful viability.

PMID- 11315269
TI  - Is there a role for high jejunostomy in the management of severe necrotising
      enterocolitis?
AB  - Necrotising enterocolitis (NEC) remains a common and severe condition affecting
      both preterm and term infants. Treatment when NEC involves a large proportion of
      the gastrointestinal tract remains controversial. We present one surgeon's
      experience of high jejunostomy (HJ) as the primary procedure in this group of
      children. HJ was performed in the presence of severe panintestinal disease. In
      those who survived, a second-look procedure and reconstruction was performed
      after 6 to 8 weeks. Over a 16-year period, 10 of 113 patients with NEC had a HJ
      constructed. Two died within 1 day due to persisting instability; the others
      survived to undergo a second-look laparotomy. Intestinal continuity was restored
      in all cases with one to five anastomoses. Three patient's died within 1 year
      from total parenteral nutrition (TPN) related cholestasis and cirrhosis. Five
      became long-term TPN-free survivors. The HJ as an initial procedure is a useful
      surgical option in neonates with severe NEC affecting the majority of the
      intestine. In this high-risk group, we achieved 50% survival from NEC.

PMID- 11315270
TI  - Acute appendicitis: the continuing role for active observation.
AB  - We present the results of a 6-year review of appendicitis. In the event of
      diagnostic doubt, a policy of active observation was instituted. This review
      endorses the validity of such a policy, indicating that it does not expose
      patients to increased morbidity. Data were collected prospectively over a 6-year
      period on 1,479 children admitted with suspected acute appendicitis (AA); 1,028
      (69.5%) were discharged with a diagnosis of non-specific abdominal pain after a
      mean observation period of 2.5 days, whilst in the remaining 451 a clinical
      diagnosis of AA was confirmed. The male-to-female ratio was equal, with no
      difference in the mean age of males (11 years) or females (12 years); 95% of
      patients were over the age of 5 years. In 324 (72%) cases surgery was performed
      on the day of admission, whilst in the remaining 126 (28%) it was deferred for 1
      to 6 days because the clinical diagnosis of AA remained doubtful. The mean
      hospital stay was 4 days (range 1-32). Analysis of the histological reports of
      all 451 cases confirmed a positive predictive value for clinical assessment alone
      of 97.9% and a normal appendicectomy rate of 2.6%. No mortality was observed;
      surgical morbidity was recorded at 6% with no correlation between postoperative
      morbidity and timing of surgery evident (Spearmans correlation coefficient = 
      0.079, p = 0.9). Active observation for suspected AA thus remains a valid
      technique for achieving an accurate diagnosis and successful outcome.

PMID- 11315271
TI  - Assessment of the colon innervation with serial biopsies above the aganglionic
      zone before the pull-through procedure in Hirschsprung's disease.
AB  - Different types of colonic dysganglionosis, and in particular intestinal neuronal
      dysplasia (IND) have been blamed for certain postoperative complications after
      surgery for Hirschsprung's disease (HD). We prospectively assessed colon
      innervation above the aganglionic zone (AZ) before proceeding to pull-through
      (PT) in order to rule-out IND as a cause of those complications. We first used a
      two-stage procedure (TSP): Full-thickness biopsies were harvested above the AZ
      and a colostomy was established during a first stage. Biopsies were assessed
      postoperatively with conventional acetyl-cholinesterase (AChE) histochemistry and
      immunohistochemistry for protein gene product 9.5 (PGP 9.5) and antigen CD56
      (CD56). Biopsies were repeated after 6 months if IND was found. When the
      innervation was normal, the PT was performed during a second stage. Since having
      refined a rapid AChE reaction, we now use a single-stage procedure (SSP).
      Biopsies are harvested above the AZ and assessed intraoperatively with rapid AChE
      staining, proceeding to PT during the same stage when the innervation is normal.
      Four patients underwent the TSP; 3 had normal innervation above the AZ and
      subsequently underwent PT. In 1 patient serial biopsies revealed IND-like
      dysganglionosis; 9 months later, the innervation was normal in repeat biopsies
      and PT was undertaken. Eleven patients underwent the SSP. Biopsies were normal in
      9 but showed unclassifiable forms of dysganglionosis in 2. As these changes were
      not typical for IND, all patients underwent PT in the same stage. Both patients
      had a poor outcome of bowel function that required a colostomy in 1 and daily
      saline irrigations in the other. IND was found in repeat biopsies made during the
      colostomy in the 1st patient and markedly hypertrophied nerves in the submucosa
      as well as ectopic nerve cells in the lamina propria in the proximal border of
      the pulled-through colon in the other. All 13 other patients have normal bowel
      function. The assessment of colon innervation above the AZ before proceeding to
      PT allows safer surgical treatment of HD. Intraoperative AChE staining is
      reliable, but due to the size and number of the biopsies, IND might be
      overlooked. Non classifiable dysganglionosis should thus be taken into account in
      the diagnosis and follow-up of the patients, as it may be clinically significant.

PMID- 11315272
TI  - Mast-cells distribution and colonic mucin composition in Hirschsprung's disease
      and intestinal neuronal dysplasia.
AB  - Intestinal neuronal dysplasia (IND) is a malformation of the enteric plexus that
      clinically resembles Hirschsprung's disease (HD). In HD, the aganglionic bowel is
      characterized by the presence of hypertrophic nerve trunks and increased numbers
      of adrenergic and cholinergic nerve fibers, whereas IND type B (IND-B) is
      characterized by dysplasia of parasympathetic nerves, hyperganglionosis, and
      giant ganglia. The aims of this study were to investigate the relationship
      between the distribution of mast cells (MC) and abnormal neuronal innervation and
      the impact of abnormal neuronal innervation on colonic epithelial differentiation
      in relation to the typical innervation abnormalities seen in HD and IND. Full
      thickness rectal-biopsy or resected surgical specimens from 15 patients (7 HD, 4
      IND, 4 control) were examined by conventional hematoxylin-eosin, periodic acid
      Schiff Alcian blue (PAS-AB), toluidine blue staining. The aganglionic and IND-B
      segments had larger numbers of MC in all layers than the ganglionic and control
      segments. There was a close relationship between the hypertrophic nerve fibers
      and the distribution of the MC. In contrast to the aganglionic segments, the
      mucin composition of the IND-B segments was normal. This finding suggests that
      innervation anomalies do not reflect epithelial differentiation to the same
      extent.

PMID- 11315273
TI  - New pathogenetic aspects of gut dysmotility in aplastic and hypoplastic desmosis
      of early childhood.
AB  - The peristaltic movement of the gut is a function of the alternating contraction
      and relaxation of circular and longitudinal muscles. This movement is induced by
      a tendon-like connective-tissue net (TCTN) in the circular and longitudinal
      muscles, which are both rooted in a connective-tissue plexus layer (CTPL). In
      children with a therapy-resistant aperistaltic or hypoperistaltic syndrome who
      had normally-developed enteric innervation, a lack of the TCTN in the muscularis
      propria was observed. Over the last 2 years, 241 children with chronic
      constipation were investigated histopathologically; 46 children surgically
      treated by partial resection of the gut or diagnostically investigated by whole
      mount biopsy. Fifteen children had a hypoperistalsis syndrome and 3 had an
      aperistalsis syndrome. All specimens were native and cut in a cryostat. Enteric
      innervation was examined by acetylcholinesterase and dehydrogenase reactions. The
      TCTN in the muscularis propria was stained with picric acid/sirius red. In the
      children with an aperistalsis syndrome, a complete lack of the TCTN in circular
      and longitudinal muscles was observed. A CTPL was not developed. The children
      with a hypoperistalsis syndrome had no CTPL, but had a partly-developed TCTN in
      the circular and longitudinal muscles, which gradually faded in the direction of
      the plexus layer. Independent of a well-developed enteric nervous system, a lack
      of the TCTN in longitudinal and circular muscles and a missing CTPL (aplastic
      desmosis) abolishes the coordinated peristaltic movement of the gut. An isolated
      lack of the CTPL in the myenteric plexus (hypoplastic desmosis) results in a
      hypoperistalsis syndrome. An anomaly of the TCTN in the muscularis propria
      disturbs gut-muscle mechanics, and is another cause of gut dysmotility.

PMID- 11315274
TI  - Histochemical and immunohistochemical study of the intrinsic innervation in
      colonic dysganglionosis.
AB  - Defective innervation of the neuromuscular junctions (NMJ) was recently described
      in intestinal neuronal dysplasia type B (IND B). The aim of the present study was
      to correlate the alterations in NMJs to other classically described parameters in
      dysganglionoses and to determine the relationship between NMJ abnormalities in
      IND B and clinical symptoms. The rectal biopsies and full-thickness colonic
      biopsy specimens of 17 patients were studied applying histochemical
      (acetylcholinesterase [AChE], lactic dehydrogenase [LDH], and succinic
      dehydrogenase [SDH] reactions) and immunohistochemical (neuronal-cell adhesion
      molecule [NCAM] and SY antibodies) methods. Thirteen patients had Hirschsprung's
      disease (HD). IND B was diagnosed in 11 (associated with HD in 8 cases, isolated
      in 2, and associated with hypoganglionosis in 1). In the aganglionic segment of
      HD there was very intense AChE activity; in contrast, NCAM- and SY-immunoreactive
      nerve fibers were markedly decreased. A spectrum of abnormalities was observed in
      IND B, usually more severe in the most distal segments: giant and immature
      ganglia in the submucous plexus were observed in all cases; heterotopic myenteric
      ganglia were frequent (72.7%); hyperganglionosis was observed in 6 (54.5%) and
      was not related to the patients' age; thick and tortuous NCAM- and SY
      immunoreactive nerve fibers, irregularly distributed in the colonic wall, were
      observed in 81.8% of the cases. No relationship was observed between
      abnormalities of NCAM- and SY-immunoreactive nerve fibers and AChE activity,
      ganglion-cell maturity, heterotopy, or the clinical symptoms presented by the
      patients with IND B. In hypoganglionism, low AChE activity and a slight decrease
      in NCAM- and SY-immunoreactive nerves were observed. Thick and tortuous,
      irregularly-distributed intrinsic NCAM- and SY-immunoreactive nerves were
      observed in every colon layer in IND B. Our results do not support IND B as a NMJ
      disorder.

PMID- 11315275
TI  - Surgical correction of pelviureteric junction obstruction in childhood--dorsal
      lumbotomy approach and selective internal ureteric stenting.
AB  - Ninety-four children (average age 3.6 years) underwent surgery for pelviureteric
      junction (PUJ) obstruction between 1994 and 1999. There were 96 operations: 94
      dismemberment pyeloplasties (2 bilateral) and 2 ureterocalycostomies. The
      surgical approach in all cases was by a dorsal lumbotomy incision. Internal
      ureteric stenting was employed selectively for solitary kidneys, inflamed renal
      pelves, long strictures, and ureterocalycostomies. The average operative time was
      57 min and the average postoperative stay in hospital was 2.5 days. Of the 94
      patients, 93 had a good outcome. Of the 78 pyeloplasties that were unstented, 7
      (9%) required stenting in the early postoperative period for urinary leak or
      obstruction. There were no wound-related complications. PUJ surgery via a dorsal
      lumbotomy approach with selective internal ureteric stenting is recommended as a
      safe and effective approach to PUJ obstruction in childhood.

PMID- 11315276
TI  - Bilateral high loop ureterostomy in the primary management of posterior urethral
      valves in a developing country.
AB  - Of 200 consecutive cases of posterior urethral valves (PUV) managed in a single
      institution, 26 underwent bilateral high loop ureterostomy (BU) as their first
      operative intervention. Indications for BU were persistently raised serum
      creatinine levels after bladder drainage, severe urosepsis, and urinary ascites,
      especially in a neonate or infant. After a median period of 1 year of diversion,
      the serum creatinine fell from a median value of 2.5 to 0.6 mg%. Twelve cases
      have been fully undiverted without deleterious effects (median serum creatinine
      level 0.5 mg%). Three patients died. Of the 14 renal units with documented
      persistent vesicoureteric reflux at the time of undiversion, only 1 has been
      reimplanted. One child has undergone bladder augmentation.

PMID- 11315277
TI  - Bilateral anterior pubic osteotomy in bladder exstrophy repair: report of
      increasing success.
AB  - Bilateral posterior iliac osteotomy is performed in most patients undergoing
      primary closure of an exstrophic bladder; the aims are to facilitate abdominal
      wall closure, prevent postoperative wound dehiscene, and possibly, to achieve
      better urinary control in older age. A new technique, anterior pelvic osteotomy
      of the superior pubic ramus, seems to obtain tension-free symphysis approximation
      safely and quickly. We report our initial experience with this osteotomy. Five
      neonates, four males and one female from 1 to 4 days old, all underwent closure
      surgery for bladder exstrophy (BE) and subsequent bilateral osteotomy of the
      superior pubic ramus (SPRO). Postoperatively, Bryant's traction was applied.
      Tension-free, complete approximation of the symphysis and uncomplicated healing
      were achieved in all five cases without palsy of the obturator nerve or
      postoperative hemorrhage. Follow-up revealed partial rediastasis with a stable
      anterior pelvic ring. Tension-free closure and immobilization are important
      factors in both initial and subsequent closure of BE. Several osteotomy
      techniques are currently in use. SPRO presents numerous advantages, namely, ease
      and rapidity, minimal blood loss, and no requirement for an extra skin incision
      or need to turn the patient on the operating table. A certain degree of
      rediastasis with growth was subsequently observed: although undesirable, this
      complication is common to all osteotomy techniques. We believe that SPRO is a
      valid and uncomplicated method to facilitate BE closure.

PMID- 11315278
TI  - The biological effect of phthalate esters on transabdominal migration of the
      testis in fetal rats in comparison with the antiandrogen flutamide.
AB  - Phthalate esters are commonly used as plasticizers for polyvinyl chloride and are
      known to be hormone-disrupting chemicals. We previously reported that mono-n
      butyl phthalate (MBP) administered to rat fetuses induced cryptorchidism
      postnatally. The aim of this study was to investigate the biological effect of
      MBP on the transabdominal migration of the testis in prenatal rats by comparing
      this with the prenatal effect of the antiandrogen flutamide on testicular
      descent. Time-pregnant Wistar King A rats were divided into three groups: group I
      rats (N = 3) were administered MBP 0.3 g/day by gavage from gestational days 15
      to 18; group II rats (N = 3) were injected with flutamide (30 mg/day) from
      gestational days 15 to 18; group III rats (N = 3) were administered solvent as
      controls. On the 19th gestational day, all rats underwent a cesarean section and
      the male fetuses were dissected to examine the position of the testis, which was
      significantly higher in the abdominal cavity in the MBP-treated rats than in
      either the flutamide-treated or control rats. No significant difference was
      observed in the position of the testis between the flutamide-treated and control
      rat fetuses. Our findings suggest that maternal MBP prevented transabdominal
      migration of the testis in prenatal rats, which may not have been due to either
      an antiandrogenic or estrogenic effect of MBP, but to a direct toxic effect of
      MBP on the testis.

PMID- 11315279
TI  - Timing of surgery in perineal ectopic testes: analysis of 16 cases.
AB  - Between 1993 and 1998, 16 patients with perineal ectopic testes (PET) (1%) were
      diagnosed among the 1,576 patients operated upon for undescended testes (UDT) in
      two pediatric surgical centers. The mean age was 23 +/- 22.5 months. The clinical
      presentation was an empty scrotum with an ipsilateral palpable perineal mass in
      16 patients and an inguinal hernia in 5. In all except 1 patient whose atrophic
      testis was removed, orchiopexy into the dartos pouch was easily performed through
      a standard inguinal skin-crease incision. The length of the testicular vessels
      and vas deferens was adequate and retroperitoneal dissection was not required.
      Although the complications of UDT are the same as for PET, the timing of surgery
      should be different. It is generally accepted that children must not be below 6
      months of age for surgical correction of UDT, but there is no need to delay
      surgery in PET, which can easily be diagnosed by physical examination in the
      neonatal period. Surgery is indicated even if there is no hernia present.

PMID- 11315280
TI  - Primary lymphedema of the penis: surgical correction by preputial unfurling.
AB  - Primary lymphedema of the penis (PLP) is a rare disease. We report a case in a 2
      year-old, uncircumcised boy where the uninvolved inner preputial skin was
      unfurled to cover the penile shaft. The uninvolved inner preputial skin is often
      elongated, and provides a suture-free cover of sufficient length for the small
      penile shaft of pediatric patients.

PMID- 11315281
TI  - Ovarian cysts in newborns.
AB  - Before the introduction of ultrasonography (US), ovarian cysts in newborns were
      thought to be rare. With the extended use of real-time US, prenatal detection has
      increased. There is still considerable controversy regarding the best treatment
      of these neonatal findings. A total of 27 instances in 24 consecutive newborns of
      antenatally-diagnosed ovarian cysts were reviewed for US data, management, and
      outcome to assess the ante- and postnatal evolution of the cyst and establish
      appropriate therapy. The cysts detected during pregnancy were studied by repeated
      postnatal US studies. In 10 children (2 with bilateral cysts) the cyst evolved
      spontaneously toward regression. Fourteen patients were operated upon; 10 had
      complex and 4 (in 1 bilateral) had simple cysts. Cystectomy was employed when
      possible to preserve the ovarian parenchyma (3 cases); in the remaining cases
      oophorectomy was performed. Histologically, the cysts were of follicular origin
      or necrosis made a diagnosis impossible. US was found to be a helpful diagnostic
      tool for simple ovarian cysts, but could not reliably distinguish between benign
      and malignant tumors if a sonographically complex lesion was present. Based on
      our experience, surgical management of ovarian cysts should be reserved to
      complex masses. Simple cysts can be monitored safely by close US follow-up;
      surgery is indicated if the cyst fails to regress after several months or becomes
      symptomatic.

PMID- 11315282
TI  - Pediatric renal transplantation: anesthesia and perioperative complications.
AB  - The appropriate choice of anesthesia for patients (pts) undergoing renal
      transplantation (Ktx) requires minimal toxicity and accurate monitoring for pts
      at high risk for metabolic, cardiovascular, and respiratory perioperative
      complications. We evaluated the anesthetic management and postoperative follow-up
      in pediatric Ktx performed in the last 12 years in our institution. From 1988 to
      1999, 75 ASA class II-III pts (45 males, 22 females) younger than 18 years
      scheduled for Ktx were studied: 49 received a graft from a cadaveric donor (CD)
      and 26 from a living donor (LD). All pts were treated with dialysis within 24 h
      before the procedure. Standard monitoring consisted of an electrocardiogram,
      central venous pressure, non-invasive arterial pressure, pulse oximetry, and
      inspiratory and expiratory gas analysis. If necessary, an arterial cannula and
      pediatric pulmonary catheter were introduced. Anesthesia was induced with sodium
      thiopental, propofol, halothane, or sevoflurane and maintained with isoflurane
      and/or fentanyl and droperidol in O2:N2O (FiO2 0.4%). As muscle relaxants
      atracurium or cisatracurium besilate were used, except in allergic pts, in whom
      vecuronium or rocuronium bromide was administered. Dopamine, 20% mannitol, and
      furosemide were used to increase diuresis. Continuous morphine and ketoralac
      infusions were used for postoperative pain relief. The surgical technique was the
      same in all cases. Complications and renal-function (RF) recovery were evaluated
      relating to CD and LD using the chi-square test; differences in mean anesthesia
      and surgical time were evaluated by Student's t-test; survival curves were
      calculated from the day of Ktx to death or last follow-up and estimated by the
      Kaplan-Meier method. Values of P below 0.05 were considered significant.
      Postoperative immunosuppressive therapy was based on cyclosporine together with
      other conventional drugs. Mean anesthesia time was 228 +/- 65 min. Mean kidney
      ischemia time for CD was 16.5 +/- 4 h. Four pts (3 CD, 1 LD) died within 72 h
      postoperatively: 3 due to cardiac failure and 1 to metabolic coma. Six pts showed
      cardiovascular and 3 had infective complications, all successfully treated. Three
      pts (2 CD, 1 LD) died within 2 to 12 months after, surgery; 10 (6 CD, 4 LD) had
      graft failure and are still alive on dialysis; 58 (38 CD, 20 LD) are alive in
      good health after a mean follow-up of 57.6 +/- 36.6 months (range 12-120 months).
      Fifteen of 26 pts younger than 12 years (21 CD and 5 LD) recovered RF
      intraoperatively (10 CD, 5 LD); 1 with CD and 1 with LD showed postoperative
      graft failure and 2 with CD died within 72 h postoperatively, 22 (18 CD and 4 LD)
      are alive in good health. This group showed no statistical difference compared to
      pts older than 12 years. Of 16 pts (15 CD and 1 LD) with body weight (BW) less
      than 25 kg, 6 showed intraoperative (5 CD, 1 LD) recovery of RF. The 3 deaths
      were all in CD pts, 2 within 72 h and one 2 months after surgery; only 1 LD had
      postoperative graft failure. Twelve pts (75%) (12 CD, 80%) are alive in good
      health. Compared to pts with BW of 25 kg or more, this group showed lower
      intraoperative recovery of RF (P < or = 0.05). No peri- and postoperative
      complications occurred in all 26 LD pts (100%). Recent advances in surgery,
      anesthesia, immunosuppression, and antimicrobial prophylaxis have made Ktx a more
      predictable procedure even in pediatric pts. For high-risk pts, mortality and
      morbidity can be controlled by accurate surgical, anesthetic, and postoperative
      management. Pts younger than 12 years and with BW less than 25 kg are more likely
      to develop peri- and postoperative complications.

PMID- 11315284
TI  - Pediatric surgical logoscript.
AB  - Pediatric surgical logoscript (PSL) was developed as a graphico-pictorial
      approach to the terminology of the specialty. It requires no more than paper,
      pencil, and imagination. The creation of two alphabetical samplers is shown to
      illustrate the technique. PSL is effective, widely applicable, and most
      promising.

PMID- 11315283
TI  - Tetrachlorodecaoxide does not jeopardize anastomotic healing: an experimental
      study in animals.
AB  - Tetrachlorodecaoxide (TCDO) is a negatively-charged complex of chlorine and
      oxygen commonly used for the treatment of infected external wounds. However, it
      displays antiadhesive properties when applied intra-abdominally. In rats, small
      bowel and a large-bowel anastomoses were performed and one-half of the animals
      received TCDO. It was found that TCDO did not alter the bursting pressures of
      small and large-bowel anastomoses at 1, 3 and 9 days postoperatively.

PMID- 11315285
TI  - Congenital esophageal stenosis: report of three cases, literature review, and a
      proposed classification.
AB  - The aim of this paper is to report three cases of congenital esophageal stenosis
      (CES) of different anatomical varieties: (1) stenosis due to tracheobronchial
      remnants (TBR) involving the lower third of the esophagus; (2) fibromuscular
      stenosis (FMS) of the middle third; and (3) a membranous diaphragm (MD) involving
      the lower third. The first two patients were treated by segmental resection of
      the esophagus and end-to-end anastomosis with dramatic relief of symptoms. The
      third responded to dilatation. CES is a rare lesion, and about 500 cases are
      reported in the literature. CES due to TBR and fibromuscular hypertrophy is
      considered a segmental stenosis, as it involves a length of the esophageal wall,
      whereas the MD consists of mucosal folds and does not involve its muscular layer.
      The clinical presentation is varied, and a high index of suspicion is essential
      to arrive at an early diagnosis. Management depends on the type and severity of
      the stenosis. Stenosis due to TBR requires segmental resection. FMS may respond
      to dilatation, but severe degrees of stenosis require segmental excision. MDs
      usually respond to dilatation or may require endoscopic excision. Segmental
      stenosis can occur as an isolated lesion or in association with esophageal
      atresia or stenosis due to a MD. Based on this observation, a classification of
      CES is proposed.

PMID- 11315286
TI  - The effect of neck flexion on oesophageal tension in the pig and its relevance to
      repaired oesophageal atresia.
AB  - The indications for postoperative ventilation and paralysis with neck flexion
      after repair of oesophageal atresia (OA) have been controversial, mainly because
      of a paucity of information on oesophageal compliance and the influence of
      posture on anastomotic tension. This study using a pig model demonstrates that
      78.8% of oesophageal lengthening occurs between full flexion and the neutral
      position, contributing to an increase in oesophageal length of about 9%.
      Compliance of the oesophagus is a linear function of the natural log of the
      tension applied. These data imply that any postural change (e.g., head and neck
      flexion) that allows the oesophagus to shorten may produce an exponential
      reduction in the tension and suggest that the manoeuvre may be appropriate in
      long-gap OA where there is considerable tension across the oesophageal
      anastomosis.

PMID- 11315287
TI  - The western Canadian experience with congenital diaphragmatic hernia: perinatal
      factors predictive of extracorporeal membrane oxygenation and death.
AB  - This study documents how congenital diaphragmatic hernia (CDH) is managed in
      level III neonatal intensive care units (NICUs) in western Canada and examines
      perinatal factors predictive of the need for extracorporeal membrane oxygenation
      (ECMO). Information was obtained retrospectively from all level III NICUs in
      western Canada about the management of infants with CDH between 1992 and 1996; 91
      infants with isolated CDH were identified. A prenatal diagnosis was made in 42
      cases (46%). Surfactant was used in 53%, high-frequency oscillation (HFO) in 29%,
      and nitric oxide (NO) in 27%. Of the 69 infants born in referral centers, 29
      (42%) were referred for possible ECMO; 17 (59%) of those required ECMO, with 65%
      survival. The overall requirement for ECMO was 30%. Death or ECMO occurred in 40%
      of cases overall. Overall survival was 82%. Survival in those needing ECMO was
      74%, and in those not needing ECMO 86%. Significant predictors of death or ECMO
      were: prenatal diagnosis (P < 0.05), maximum postductal arterial partial pressure
      of oxygen (PaO2) < 100 mmHg (P < 0.001), and an oxygenation index (OI) at 6 h >
      15 (P < 0.001). In cases where there is a prenatal diagnosis of CDH the mother
      should deliver at an ECMO center. Alternatively, an OI of > 15 at 6 h and PaO2 <
      100 mmHg should prompt referral to an ECMO center.

PMID- 11315288
TI  - Neonatal pertussis requiring extracorporeal membrane oxygenation.
AB  - Despite widespread immunization against Bordetella pertussis, whooping cough
      remains potentially fatal in susceptible populations such as neonates. A case of
      neonatal pertussis with severe pulmonary hypertension (PH) requiring
      extracorporal membrane oxygenation (ECMO) is described. PH associated with
      pertussis severe enough to require ECMO is frequently irreversible and associated
      with a poor prognosis.

PMID- 11315289
TI  - Postoperative tension pneumoperitoneum in an infant.
AB  - A 9-week-old boy developed massive postoperative abdominal distension following a
      Fredet-Ramstedt pyloromyotomy for hypertrophic pyloric stenosis. A plain
      abdominal X-ray film was suggestive of a tension pneumoperitoneum. Passage of a
      cannula into the peritoneal space resulted in forceful expulsion of air,
      resulting in relief of the distension, which recurred after a few hours. At
      laparotomy, the tension pneumoperitoneum was due to a pyloric fistula at the
      proximal end of the pyloromyotomy, although a mucosal breach at the first
      operation had been at the distal end. Closure of the fistula resulted in complete
      resolution. A limited review of the literature is undertaken.